PMID- 18065664
TI  - Parenteral immunization of mice with a genetically inactivated pertussis toxin
      DNA vaccine induces cell-mediated immunity and protection.
AB  - The immunogenicity and protective efficacy of a DNA vaccine encoding a
      genetically inactivated S1 domain of pertussis toxin was evaluated using a murine
      respiratory challenge model of Bordetella pertussis infection. It was found that
      mice immunized via the intramuscular route elicited a purely cell-mediated immune
      response to the DNA vaccine, with high levels of gamma interferon (IFN-gamma) and
      interleukin (IL)-2 detected in the S1-stimulated splenocyte supernatants and no
      serum IgG. Despite the lack of an antibody response, the lungs of DNA-immunized
      mice were cleared of B. pertussis at a significantly faster rate compared with
      mock-immunized mice following an aerosol challenge. To gauge the true potential
      of this S1 DNA vaccine, the immune response and protective efficacy of the
      commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccine were included as
      the gold standard. Immunization with DTaP elicited a typically strong T-helper
      (Th)2-polarized immune response with significantly higher titres of serum IgG
      than in the DNA vaccine group, but a relatively weak Th1 response with low levels
      of IFN-gamma and IL-2 detected in the supernatants of antigen-stimulated
      splenocytes. DTaP-immunized mice cleared the aerosol challenge more efficiently
      than DNA-immunized mice, with no detectable pathogen after day 7 post-challenge.

PMID- 18065665
TI  - Diagnostic value of DNA and (1-->3)- beta-D-glucan detection in serum and
      bronchoalveolar lavage of mice experimentally infected with Fusarium oxysporum.
AB  - A sensitive and highly specific nested PCR (nPCR) protocol was developed for the
      specific detection of Fusarium oxysporum DNA in clinical specimens. The
      diagnostic value of F. oxysporum-specific DNA and (1-->3)-beta-D-glucan (BDG)
      detection was subsequently evaluated in serum and bronchoalveolar lavage (BAL)
      specimens of mice infected intravenously with F. oxysporum conidia. Mice were
      sacrificed in groups of six daily up to day 8 and then on days 11 and 14. The F.
      oxysporum-specific DNA and BDG in serum and BAL specimens were detected using
      nPCR and a Fungitell kit, respectively. Cultures of lung homogenate of all of the
      infected animals yielded F. oxysporum and the fungus was also observed in
      KOH/Calcofluor mounts of 67 % of the tissues. The BDG (cut-off value 80 pg ml(
      1)) and nPCR sensitivity in BAL and serum specimens was 15 and 98 %, and 92 and
      75 %, respectively. Combined detection of F. oxysporum DNA and BDG in serum
      enhanced the sensitivity to 98 %. However, the kinetics of the two markers were
      slightly different. Whilst BDG positivity in serum remained high throughout the
      infection period, nPCR positivity declined slowly. The data obtained in this
      study suggest that combined detection of BDG and DNA in serum offers a sensitive
      and specific diagnostic approach for invasive Fusarium infection.

PMID- 18065666
TI  - A hospital-wide study of the impact of introducing a personal data assistant
      augmented blood culture round.
AB  - Blood culture is the cornerstone of an established aetiological diagnosis of
      septicaemia. The automated blood culture systems used for this purpose have
      changed little in the last decade, and the clinical value of results depends on a
      variety of factors, including pre- and post-analytical variables. Growing
      scepticism over the value of blood culture results and pressure for the
      introduction of molecular detection systems have prompted a critical path
      analysis of pre-, peri- and post-analytical stages in the generation of positive
      blood culture results. The impact of a positive blood culture was studied in a
      teaching hospital for 12 months before and 12 months after the introduction of a
      microbiologist's blood culture round. Active culture reporting via a blood
      culture ward round was supported by a personal data assistant database of
      contemporaneous laboratory and clinical data. Hospital occupancy and death
      register records were subsequently obtained through the State Government data
      linkage project. There was no evidence that faster laboratory generation of
      positive blood culture results, faster reporting of results or direct clinical
      interaction with the patient's primary medical team reduced the risk of death in
      hospital. However, there was a threefold increase in the rate of death in
      hospital following a 1 day delay in collection of blood cultures after hospital
      admission (P=0.0010). The overall duration of hospital stay for patients with a
      positive blood culture fell by 2.5 days compared with the previous 12 month
      period (P=0.0003). The interval between the initial positive culture result and
      patient discharge fell by 2 days (P=0.0010). This difference was attributed to
      shorter overall admissions and shorter intervals between positive cultures
      containing Gram-positive cocci and subsequent patient discharge (P=0.0018). An
      increased mortality rate from community-acquired bacteraemic infections was
      associated with delayed culture collection, but not with a prolonged laboratory
      processing interval. Thus, the speed of conventional blood culture analysis and
      the form of clinical reporting have little direct effect on the clinical outcome
      of bacteraemia, but may contribute to a reduction in the length of hospital
      admission. Introduction of molecular identification tests, such as multiplex PCR
      methods, at the Gram-stain stage of blood culture is unlikely to affect the rate
      of death in hospital, but may reduce the length of hospital admission.

PMID- 18065667
TI  - Development of a loop-mediated isothermal amplification method for diagnosing
      Pneumocystis pneumonia.
AB  - Loop-mediated isothermal amplification (LAMP) is a novel, rapid nucleic acid
      amplification method with high specificity and sensitivity under isothermal
      conditions. In this study a LAMP assay for diagnosing Pneumocystis pneumonia
      (PCP) was developed. Oligonucleotide primers specific for Pneumocystis species
      were designed corresponding to 18S rRNA gene sequences. The assay, performed for
      30 min at 61 degrees C, was capable of detecting 50 copies per tube (2 x 10(3)
      copies ml(-1)) in 30 min and did not show cross-reactivity to other species of
      fungi, including the genera Candida, Aspergillus and Cryptococcus. A total of 21
      of 24 clinical specimens (sputum and bronchoalveolar lavage fluid) from patients
      with suspected PCP tested positive using the LAMP assay by real-time fluorescence
      detection. The results of the LAMP reaction were also observed by real-time
      turbidity detection and end-point visual turbidity or fluorescence detection.
      With real-time fluorescence detection, melting curves of the products were
      effective at distinguishing specific amplification from non-specific
      amplification or self-amplification. Visual detection was also possible as a
      rapid and easy assay using only a heat block and a black light.

PMID- 18065668
TI  - Molecular typing of Japanese Escherichia coli O157 : H7 isolates from clinical
      specimens by multilocus variable-number tandem repeat analysis and PFGE.
AB  - The multilocus variable-number tandem repeat analysis (MLVA) method to target
      eight variable-number tandem repeat loci, based on agarose gel electrophoresis
      separation of multiplexed PCR products, and the PFGE method were applied to
      clinical isolates of Escherichia coli O157 : H7 with the aim of comparing their
      performance as methods of typing this bacterium. Using MLVA, a total of 57
      isolates from patients in Shizuoka prefecture, Japan, were divided into 20 types
      and classified into 23 PFGE types. Twenty-four isolates from four sporadic
      infections, four household contact infections and one outbreak that occurred in
      central parts of Shizuoka prefecture during August to November in 2005 were shown
      to be the same MLVA type, and most of the isolates had identical PFGE banding
      patterns, suggesting the diffuse outbreak in these parts of Japan. Thus, there
      was a good correlation between MLVA types and PFGE types, with both methods
      displaying broadly similar discriminatory powers. However, the MLVA typing proved
      to be a much easier and more rapid method for the analysis of E. coli O157 : H7
      strain relatedness to identify transmission routes. Hence, our MLVA method would
      be a suitable technique for routine typing in many laboratories, including public
      health agencies, and even in hospitals.

PMID- 18065669
TI  - Specific detection and differentiation of Ochrobactrum anthropi, Ochrobactrum
      intermedium and Brucella spp. by a multi-primer PCR that targets the recA gene.
AB  - Ochrobactrum anthropi, Ochrobactrum intermedium and Brucella spp. are
      phenotypically and genetically closely related pathogens that may cause disease
      with similar clinical presentation. Consequently, difficulties in their
      identification and differentiation have been reported. In this study, a sensitive
      recA gene-based multi-primer single-target PCR (MP-ST-PCR) was developed that
      allowed the specific detection and differentiation of these clinically relevant
      pathogens. The specificity of the assay was evaluated using a representative
      panel of 50 O. anthropi and 16 O. intermedium strains and the type strains of all
      Brucella spp. Detection limits for purified DNA from O. anthropi, O. intermedium
      and Brucella melitensis were 100, 10 and 100 fg, respectively. Brucella DNA was
      also successfully detected in various clinical specimens from a human patient
      with culture-proven brucellosis and from a Brucella-infected sheep and its
      aborted fetuses. The sensitivity of the MP-ST-PCR was comparable to that of an
      evaluated in-house Brucella real-time PCR assay. The developed assay closes a
      diagnostic gap and provides a simple but robust tool for the sensitive detection
      and correct identification of O. anthropi, O. intermedium and Brucella spp.

PMID- 18065670
TI  - Identification and characterization of a vancomycin-resistant Staphylococcus
      aureus isolated from Kolkata (South Asia).
AB  - A pathogenic vancomycin-resistant Staphylococcus aureus (VRSA) isolate (MIC > or
      =64 microg ml(-1)) was obtained from a Kolkata hospital in June 2005. Species
      identification was confirmed by Gram staining, standard biochemical tests and PCR
      amplification of the nuc gene, which encodes the thermostable nuclease that is
      highly specific for S. aureus. The VRSA isolate was also resistant to beta
      lactams (amoxicillin, ampicillin, cefepime, cefotaxime, cefuroxime, cephalexin
      and meticillin), chloramphenicol, streptomycin, macrolides (erythromycin and
      roxithromycin), clindamycin, rifampicin and trimethoprim-sulfamethoxazole.
      However, the isolate was susceptible to gentamicin (an aminoglycoside) and
      ciprofloxacin (a fluoroquinolone). The resistance to vancomycin was inducible in
      vitro, because the MIC of vancomycin increased from 64 microg ml(-1) initially to
      1024 microg ml(-1) during culture of this VRSA strain in the presence of
      vancomycin. The VRSA isolate contained a large plasmid ( approximately 53.4 kb)
      and four small plasmids of approximately 6, 5.5, 5.1 and 1.5 kb. The large
      plasmid of approximately 53.4 kb harboured the vancomycin-resistance genes
      vanHAX, which was confirmed by PCR amplification using the same plasmid as
      template and, separately, primers specific for the 2.61 kb vanHAX gene cluster,
      vanH (969 bp), vanA (1032 bp) and vanX (609 bp). The VRSA isolate was also
      positive for mecA. Vancomycin resistance was successfully transferred from this
      VRSA donor to a vancomycin-sensitive recipient S. aureus clinical isolate by a
      broth mating procedure. The MIC of vancomycin for the transconjugant was 32
      microg ml(-1), as against 2 microg ml(-1) for the parent strain. Nucleotide
      sequencing of the PCR product showed partial homology with van genes of an
      enterococcal transposon Tn1546-like element. This is believed to be the first
      Indian S. aureus isolate that has been shown to be phenotypically vancomycin
      resistant, presumably due to a vanHAX analogue.

PMID- 18065671
TI  - A cross-reactive neisserial antigen encoded by the NMB0035 locus shows high
      sequence conservation but variable surface accessibility.
AB  - The meningococcal NMB0035 locus encodes a 47 kDa outer-membrane protein that is
      highly conserved antigenically, and is able to induce antibodies during infection
      and bactericidal responses in vitro. This study analysed the surface exposure of
      this protein using specific antibodies in flow cytometry assays and determined
      its nucleotide sequence in 33 Neisseria strains. Genomic analyses revealed no
      significant differences in the nucleotide or amino acid sequences, but flow
      cytometry showed that surface accessibility was highly variable among the
      strains. These results suggest that masking by and/or association with lipo
      oligosaccharides or other membrane molecules can be crucial for antigen
      accessibility, which must be thoroughly analysed in new vaccine candidates.

PMID- 18065672
TI  - Analysis of the antimicrobial activity of local anaesthetics used for dental
      analgesia.
AB  - Seven local anaesthetics and their active anaesthetic components [Ultracaine D-S
      (articaine hydrochloride), Carbostesin (bupivacaine hydrochloride), Scandicaine
      (mepivacaine hydrochloride), Xylonest (prilocaine hydrochloride), Xylocaine
      (lidocaine hydrochloride), Hostacaine (butanilicaine phosphate) and Novocaine
      (procaine hydrochloride)] were tested for their antimicrobial activity against
      311 bacterial strains from 52 different species and 14 Candida albicans strains.
      The tested pathogens were members of the oral flora, and partly members of the
      skin and intestinal flora. Additionally, the antimicrobial activity of methyl-4
      hydroxybenzoate, sodium disulfite, adrenaline hydrogen tartrate and adrenaline
      (the preservative and vasoconstrictive components of the anaesthetics) was
      tested. For determination of MIC and minimal bactericidal concentration (MBC),
      the agar dilution method using Wilkins-Chalgren agar was applied. The trade
      preparation Ultracaine D-S showed the most prominent antimicrobial activity with
      regard to both MIC and MBC. Ultracaine D-S and its active substance, articaine
      hydrochloride, showed similar MIC values, suggesting that the antimicrobial
      activity is mainly caused by the anaesthetic component. Novocaine showed the
      lowest antimicrobial activity and did not inhibit 35 of the species tested. The
      MIC values of all local anaesthetics were between 0.25 and 16 mg ml(-1). The
      routinely applied concentration of Ultracaine D-S was roughly four times higher,
      and of Hostacaine was two times higher, than the MBC values for the tested
      bacteria, whereas for the other anaesthetics, the MBC values were not reached or
      exceeded with the concentrations used. The MIC range of the preservatives was 0.5
      1.0 mg ml(-1) for methyl-4-hydroxybenzoate and 0.2-0.5 mg ml(-1) for sodium
      disulfite. The articaine MIC values were two to three serial dilution steps
      lower, and the butanilicaine MIC values one to two serial dilution steps lower,
      than the MIC of the preservatives. The mepivacaine mean MIC values were slightly
      lower for Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas
      gingivalis and Staphylococcus aureus, but higher for Streptococcus intermedius,
      compared with the preservative methyl-4-hydroxybenzoate. The same result was
      found with Streptococcus intermedius and lidocaine. Screening of 20 MIC values of
      4 pure anaesthetic substances and the corresponding preservative found 2/20
      instances where the MICs of the preservatives against 5 representative species
      (67 strains) were lower, indicating that the antimicrobial effect was mainly due
      to the preservative, but 18/20 results where the pure anaesthetic component
      showed greater antimicrobial effects compared with the preservative. The in vitro
      results for Carbostesin, Scandicaine and especially for Novocaine indicate that a
      local disinfection should be done prior to injection of the anaesthetics. Due to
      the results obtained with nosocomial strains (Escherichia coli, S. aureus and
      Pseudomonas), disinfection of the mucous membranes should be performed routinely
      in immunocompromised patients, regardless of the anaesthetic used.

PMID- 18065673
TI  - Occurrence of staphylococci in the oral cavities of healthy adults and nasal oral
      trafficking of the bacteria.
AB  - To investigate a possible peroral route of infective endocarditis (IE), the
      occurrence of staphylococci in the oral cavity was examined using saliva and
      supragingival plaque specimens from 56 systemically and periodontally healthy
      adults aged 22-43 years old (27.1+/-5.3). Nine Staphylococcus species and 334
      isolates were identified. In saliva, the total occurrence rate was 83.9 % and the
      total number of bacteria was 10(2)-10(4) c.f.u. ml(-1). Staphylococcus aureus was
      the most frequent species (46.4 %), followed by Staphylococcus epidermidis (41.1
      %) and others (Staphylococcus hominis, Staphylococcus warneri, Staphylococcus
      intermedius, Staphylococcus capitis, Staphylococcus haemolyticus, Staphylococcus
      lugdunensis and Staphylococcus gallinarum, isolation frequencies ranging in order
      from 12.5 to 1.8 %). A similar isolation tendency was observed in supragingival
      plaque, with a total occurrence rate of 73.2 % and amounts of bacteria ranging
      from 10(2) to 10(5) c.f.u. g(-1). Four common Staphylococcus species (S. aureus,
      S. epidermidis, S. lugdunensis and S. hominis) were isolated from nasal swab
      samples taken from the oral staphylococci-positive subjects. Genotyping of all 18
      combinations of oral- and nasal-derived isolates by PFGE indicated that identical
      clones or close relatives were commonly distributed in these two cavities. Since
      the provision of micro-organisms from the nasal cavity was shown and occurrence
      rates in the oral cavity were adequate, these results suggest a possible peroral
      route of staphylococcal IE, as in cases of viridans streptococcal IE.

PMID- 18065674
TI  - Oral administration of a catalase-producing Lactococcus lactis can prevent a
      chemically induced colon cancer in mice.
AB  - Reactive oxygen species, such as hydrogen peroxide (H2O2), are involved in
      various aspects of tumour development. Decreasing their levels can therefore be a
      promising approach for colon cancer prevention. The objective of this study was
      to evaluate the effect of catalase-producing Lactococcus lactis on the prevention
      of an experimental murine 1,2-dimethylhydrazine (DMH)-induced colon cancer. DMH
      treated BALB/c mice received either a catalase-producing L. lactis strain or the
      isogenic non-catalase-producing strain as a control, whereas other untreated mice
      did not receive bacterial supplementation. Catalase activity and H2O2 levels in
      intestinal fluids and blood samples were measured, and changes in the histology
      of the large intestines during tumour progression were evaluated. The catalase
      producing L. lactis strain used in this study was able to slightly increase
      catalase activities in DMH-treated mice (1.19+/-0.08 U ml(-1)) and reduce H2O2
      levels (3.4+/-1.1 microM) compared to (i) animals that received the non-catalase
      producing strain (1.00+/-0.09 U ml(-1), 9.0+/-0.8 microM), and (ii) those that
      did not receive bacterial supplementation (1.06+/-0.07 U ml(-1), 10.0+/-1.1
      microM). Using the histopathological grading scale of chemically induced
      colorectal cancer, animals that received the catalase-producing L. lactis had a
      significantly lesser extent of colonic damage and inflammation (2.0+/-0.4)
      compared to animals that received the non-catalase-producing L. lactis (4.0+/
      0.3) or those that did not receive bacterial supplementation (4.7+/-0.5). The
      catalase-producing L. lactis strain used in this study was able to prevent tumour
      appearance in an experimental DMH-induced colon cancer model.

PMID- 18065675
TI  - Development of a novel ex vivo insect model for studying virulence determinants
      of Escherichia coli K1.
AB  - A key step in Escherichia coli K1 meningitis is the crossing of the blood-brain
      barrier by the bacteria in order to gain entry into the central nervous system
      (CNS). In this study, a novel ex vivo model to study E. coli K1 invasion of the
      CNS is described that uses the African migratory locust, Locusta migratoria. By
      injecting bacteria into isolated locust head capsules, it was demonstrated that
      E. coli K1 invade the locust brain within 2 h in numbers depending on the
      concentration of bacteria injected. Using several mutants derived from K1, it was
      shown that outer-membrane protein A is a critical bacterial determinant required
      for the E. coli K1 invasion. The isogenic gene-deletion mutants, DeltafimH,
      Deltacnf1, DeltaneuDB and a rough LPS mutant showed significantly reduced
      invasion of locust brain. This novel model for the study of E. coli K1
      pathogenesis offers several advantages over existing mammalian models in relation
      to its relative ease of use, cost-effectiveness and ethical acceptability.

PMID- 18065676
TI  - Differential clustering of bowel biopsy-associated bacterial profiles of
      specimens collected in Mexico and Canada: what do these profiles represent?
AB  - Bowel commensals appear to be an important source of antigens that drive the
      chronic immune inflammation characteristic of Crohn's disease and ulcerative
      colitis [inflammatory bowel diseases (IBD)]. Biopsy-associated bacteria are
      assumed to be particularly relevant in bacteriological investigations of IBD
      because they are assumed to be located on the mucosal surface and hence close to
      immunological cells. This investigation analysed the bacterial collections
      associated with bowel biopsies, aspirates of residual fluid after bowel cleansing
      and faeces from IBD patients and non-IBD subjects in Edmonton, Canada, and Mexico
      City, Mexico. Temporal temperature gradient gel electrophoresis of 16S rRNA gene
      sequences produced profiles of the bacterial collections and their similarities
      were compared. Similarity analysis showed that the profiles did not cluster
      according to disease status, but that Canadian and Mexican profiles could be
      differentiated by this method. Comparison of biopsy, aspirate and faecal samples
      obtained from the same subject showed that, on average, the profiles were highly
      similar. Therefore, biopsy-associated bacteria are likely to represent, at least
      in part, contaminants from the fluid, which resembles a faecal solution, that
      pools in the bowel after cleansing prior to endoscopy.

PMID- 18065677
TI  - Infection by Panton-Valentine leukocidin-producing Staphylococcus aureus
      clinically mimicking Lemierre's syndrome.
AB  - Lemierre's syndrome is an oropharyngeal infection which leads to severe septic
      thrombophlebitis of the internal jugular vein and metastatic abscesses of the
      lungs and other organs. It is usually caused by Fusobacterium necrophorum, a Gram
      negative obligate anaerobe. An unusual case of Panton-Valentine leukocidin (PVL)
      producing Staphylococcus aureus infection masquerading as Lemierre's syndrome is
      reported here. A 32-year-old fit and otherwise healthy male presented on
      Christmas morning with a boil on his left cheek for 2 days and generalized rash
      for 3 h. His general condition began to worsen, he developed facial swelling and
      loss of vision in the left eye and was transferred to the intensive care unit.
      His treatment was taken over by team of specialists and further investigations
      revealed thrombophlebitis of the left internal jugular vein and cavernous sinus
      thrombosis with multiple brain infarcts and lung abscesses. His condition
      remained critical with multiple cranial nerve involvement despite being on broad
      spectrum antibiotics. Blood cultures grew S. aureus which was producing PVL
      toxin. He improved gradually over several weeks. He underwent intensive
      physiotherapy and made a good recovery. Although a rare entity, it is important
      to consider Lemierre's syndrome in septic patients who present with rapidly
      worsening symptoms.

PMID- 18065678
TI  - Upper and lower urinary tract infection caused by Klebsiella pneumoniae serotype
      K2 and CTX-M-15 beta-lactamase-producing serotype K1: a case report and
      characterization of serum killing resistance.
AB  - CTX-M-15 beta-lactamase-producing Klebsiella pneumoniae serotype K1 was isolated
      from a patient with fatal upper urinary tract infection (UTI) complicated by
      sepsis caused by K. pneumoniae serotype K2. Transfer of a CTX-M-15 beta-lactamase
      plasmid from the K1 to the K2 strain was observed. However, plasmid acquisition
      by the K2 strain did not occur in vivo, suggesting that the K1 strain might not
      have contributed directly to the upper UTI. In addition, effects of K serotypes
      and plasmid acquisition on K. pneumoniae serum resistance were examined.

PMID- 18065679
TI  - Citrobacter freundii peritonitis and tunnel infection in a patient on continuous
      ambulatory peritoneal dialysis.
AB  - The clinical course of a patient on continuous ambulatory peritoneal dialysis who
      developed peritonitis and tunnel infection due to an unusual pathogen,
      Citrobacter freundii, is described. The patient did not respond well to
      antibiogram-based therapy (intravenous meropenem and intraperitoneal gentamicin)
      and removal of the catheter was required.

PMID- 18065680
TI  - Efficacy of pre-operative cephalosporin prophylaxis in controlling pathogenic
      oral bacteria growth in comatose patients.

PMID- 18065681
TI  - Performance of a lateral flow test for the detection of leprosy patients in
      India.

PMID- 18065682
TI  - Detection and characterization of Leptospira interrogans isolates from pet rats
      belonging to a human immunodeficiency virus-positive patient with leptospirosis.

PMID- 18065683
TI  - Xanthine in urine stimulates growth of Leishmania promastigotes in vitro.

PMID- 18065684
TI  - A novel high-throughput screening system identifies a small molecule repressive
      for matrix metalloproteinase-9 expression.
AB  - Aberrant gene expression is one of the driving forces for cancer progression and
      is considered an ideal target for chemical intervention. Although emerging
      bioluminescence reporter systems allow high-throughput searches for small
      molecules regulatory for gene expression, frequent silencing of reporter genes by
      epigenetic mechanisms hinders wide application of this drug discovery strategy.
      Here we report a novel system that directs the integration of a promoter-reporter
      construct to an open chromosomal location by Flp-mediated homologous
      recombination, thereby overcoming reporter-gene silencing. Using this system, we
      have screened more than 8000 compounds in the DIVERSet chemical library for
      repressors of a matrix metalloproteinase-9 (MMP-9) promoter and identified 5
      methyl-2-(4-methylphenyl)-1H-benzimidazole (MPBD) inhibitory for MMP-9 gene
      expression. Consistent with this effect, MPBD inhibits MMP-9-dependent invasion
      of UMSCC-1 oral cancer cells, preosteoclast migration, and receptor activator of
      nuclear factor-kappaB ligand-induced osteoclast activity over concentration
      ranges that repressed MMP-9 expression. Mechanistic studies indicated that MPBD
      antagonizes AP-1 function by inhibiting its transactivation activity. We conclude
      that the Flp-mediated homologous recombination system to direct reporter
      integration into open chromatin regions represents a novel strategy allowing for
      the development of high-throughput systems screening for lead compounds targeting
      aberrant gene expression in cancer.

PMID- 18065685
TI  - From CNI-1493 to the immunological homunculus: physiology of the inflammatory
      reflex.
AB  - The inflammatory reflex is a neurophysiological mechanism that regulates the
      immune system. The efferent branch of the reflex the cholinergic anti
      inflammatory pathway, which inhibits inflammation by suppressing cytokine
      synthesis via release of acetylcholine in organs of the reticuloendothelial
      system, including the spleen, liver, and gastrointestinal tract. Acetylcholine
      binds to alpha7 nicotinic acetylcholine receptors expressed by macrophages and
      other cytokine-producing cells. Receptor-ligand engagement suppresses
      proinflammatory cytokines and prevents tissue damage. Herein is a review of some
      of the experimental studies that define the inflammatory reflex and its anatomic
      and physiologic components.

PMID- 18065686
TI  - Cytokinins act directly on lateral root founder cells to inhibit root initiation.
AB  - In Arabidopsis thaliana, lateral roots are formed from root pericycle cells
      adjacent to the xylem poles. Lateral root development is regulated
      antagonistically by the plant hormones auxin and cytokinin. While a great deal is
      known about how auxin promotes lateral root development, the mechanism of
      cytokinin repression is still unclear. Elevating cytokinin levels was observed to
      disrupt lateral root initiation and the regular pattern of divisions that
      characterizes lateral root development in Arabidopsis. To identify the stage of
      lateral root development that is sensitive to cytokinins, we targeted the
      expression of the Agrobacterium tumefaciens cytokinin biosynthesis enzyme
      isopentenyltransferase to either xylem-pole pericycle cells or young lateral root
      primordia using GAL4-GFP enhancer trap lines. Transactivation experiments
      revealed that xylem-pole pericycle cells are sensitive to cytokinins, whereas
      young lateral root primordia are not. This effect is physiologically significant
      because transactivation of the Arabidopsis cytokinin degrading enzyme cytokinin
      oxidase 1 in lateral root founder cells results in increased lateral root
      formation. We observed that cytokinins perturb the expression of PIN genes in
      lateral root founder cells and prevent the formation of an auxin gradient that is
      required to pattern lateral root primordia.

PMID- 18065687
TI  - A CRM domain protein functions dually in group I and group II intron splicing in
      land plant chloroplasts.
AB  - The CRM domain is a recently recognized RNA binding domain found in three group
      II intron splicing factors in chloroplasts, in a bacterial protein that
      associates with ribosome precursors, and in a family of uncharacterized proteins
      in plants. To elucidate the functional repertoire of proteins with CRM domains,
      we studied CFM2 (for CRM Family Member 2), which harbors four CRM domains. RNA
      coimmunoprecipitation assays showed that CFM2 in maize (Zea mays) chloroplasts is
      associated with the group I intron in pre-trnL-UAA and group II introns in the
      ndhA and ycf3 pre-mRNAs. T-DNA insertions in the Arabidopsis thaliana ortholog
      condition a defective-seed phenotype (strong allele) or chlorophyll-deficient
      seedlings with impaired splicing of the trnL group I intron and the ndhA, ycf3
      int1, and clpP-int2 group II introns (weak alleles). CFM2 and two previously
      described CRM proteins are bound simultaneously to the ndhA and ycf3-int1 introns
      and act in a nonredundant fashion to promote their splicing. With these findings,
      CRM domain proteins are implicated in the activities of three classes of
      catalytic RNA: group I introns, group II introns, and 23S rRNA.

PMID- 18065688
TI  - Plastid signals remodel light signaling networks and are essential for efficient
      chloroplast biogenesis in Arabidopsis.
AB  - Plastid signals are among the most potent regulators of genes that encode
      proteins active in photosynthesis. Plastid signals help coordinate the expression
      of the nuclear and chloroplast genomes and the expression of genes with the
      functional state of the chloroplast. Here, we report the isolation of new
      cryptochrome1 (cry1) alleles from a screen for Arabidopsis thaliana genomes
      uncoupled mutants, which have defects in plastid-to-nucleus signaling. We also
      report genetic experiments showing that a previously unidentified plastid signal
      converts multiple light signaling pathways that perceive distinct qualities of
      light from positive to negative regulators of some but not all photosynthesis
      associated nuclear genes (PhANGs) and change the fluence rate response of PhANGs.
      At least part of this remodeling of light signaling networks involves converting
      HY5, a positive regulator of PhANGs, into a negative regulator of PhANGs. We also
      observed that mutants with defects in both plastid-to-nucleus and cry1 signaling
      exhibited severe chlorophyll deficiencies. These data show that the remodeling of
      light signaling networks by plastid signals is a mechanism that plants use to
      integrate signals describing the functional and developmental state of plastids
      with signals describing particular light environments when regulating PhANG
      expression and performing chloroplast biogenesis.

PMID- 18065689
TI  - Cytokinin regulates type-A Arabidopsis Response Regulator activity and protein
      stability via two-component phosphorelay.
AB  - The plant hormone cytokinin regulates many aspects of growth and development.
      Cytokinin signaling involves His kinase receptors that perceive cytokinin and
      transmit the signal via a multistep phosphorelay similar to bacterial two
      component signaling systems. The final targets of this phosphorelay are a set of
      Arabidopsis thaliana Response Regulator (ARR) proteins containing a receiver
      domain with a conserved Asp phosphorylation site. One class of these, the type-A
      ARRs, are negative regulators of cytokinin signaling that are rapidly
      transcriptionally upregulated in response to cytokinin. In this study, we tested
      the role of phosphorylation in type-A ARR function. Our results indicate that
      phosphorylation of the receiver domain is required for type-A ARR function and
      suggest that negative regulation of cytokinin signaling by the type-A ARRs most
      likely involves phosphorylation-dependent interactions. Furthermore, we show that
      a subset of the type-A ARR proteins are stabilized in response to cytokinin in
      part via phosphorylation. These studies shed light on the mechanism by which type
      A ARRs act to negatively regulate cytokinin signaling and reveal a novel
      mechanism by which cytokinin controls type-A ARR function.

PMID- 18065690
TI  - Interaction between SGT1 and cytosolic/nuclear HSC70 chaperones regulates
      Arabidopsis immune responses.
AB  - The conserved eukaryotic protein SGT1 (for Suppressor of G2 allele of skp1) has
      characteristics of an HSP90 (for heat shock protein 90 kD) cochaperone and in
      plants regulates hormone responses and Resistance gene-triggered immunity. We
      affinity-purified SGT1-interacting proteins from Arabidopsis thaliana leaf
      extracts and identified by mass spectrometry cytosolic heat shock cognate 70
      (HSC70) chaperones as the major stable SGT1 interactors. Arabidopsis SGT1a and
      SGT1b proteins associate with HSC70 in vivo and distribute with HSC70 in the
      cytosol and nucleus. An intact C-terminal SGT1-specific (SGS) domain that is
      required for all known SGT1b functions in immunity and development is needed for
      HSC70 interaction and for the nuclear accumulation of SGT1b. Interaction assays
      of transiently expressed proteins or their domains in Nicotiana benthamiana point
      to a role of SGT1 as a HSC70 cofactor. Expression of two HSC70 isoforms is
      upregulated by pathogen challenge, and while loss of function of individual
      cytosolic HSC70 genes has no defense phenotype, HSC70-1 overexpression disables
      resistance to virulent and avirulent pathogens. Moreover, mutations in SGT1b lead
      to a similar degree of heat shock tolerance as deregulation of HSC70-1. We
      conclude that an HSC70-SGT1 chaperone complex is important for multiple plant
      environmental responses and that the evolutionarily conserved SGS domain of SGT1
      is a key determinant of the HSC70-SGT1 association.

PMID- 18065691
TI  - The basic helix-loop-helix transcription factor PIF5 acts on ethylene
      biosynthesis and phytochrome signaling by distinct mechanisms.
AB  - PHYTOCHROME-INTERACTING FACTOR5 (PIF5), a basic helix-loop-helix transcription
      factor, interacts specifically with the photoactivated form of phytochrome B
      (phyB). Here, we report that dark-grown Arabidopsis thaliana seedlings
      overexpressing PIF5 (PIF5-OX) exhibit exaggerated apical hooks and short
      hypocotyls, reminiscent of the triple response induced by elevated ethylene
      levels, whereas pif5 mutants fail to maintain tight hooks like those of wild-type
      seedlings. Silver ions, an ethylene receptor blocker, rescued the triple-response
      phenotype, and we show that PIF5-OX seedlings express enhanced levels of key
      ethylene biosynthesis enzymes and produce elevated ethylene levels. Exposure of
      PIF5-OX seedlings to prolonged continuous red light (Rc) promotes hypocotyl
      elongation relative to dark controls, the reciprocal of the Rc-imposed hypocotyl
      inhibition displayed by wild-type seedlings. In contrast with this PIF5-OX
      hyposensitivity to Rc, pif5 mutant seedlings are hypersensitive relative to wild
      type seedlings. We show that this contrast is due to reciprocal changes in phyB
      protein levels in prolonged Rc. Compared with wild-type seedlings, PIF5-OX
      seedlings have reduced, whereas pif5 mutants have increased, phyB (and phyC)
      levels in Rc. The phyB degradation in the overexpressors depends on a functional
      phyB binding motif in PIF5 and involves the 26S proteasome pathway. Our data thus
      indicate that overexpressed PIF5 causes altered ethylene levels, which promote
      the triple response in darkness, whereas in the light, the interaction of
      photoactivated phyB with PIF5 causes degradation of the photoreceptor protein.
      The evidence suggests that endogenous PIF5 negatively regulates phyB-imposed
      hypocotyl inhibition in prolonged Rc by reducing photoreceptor abundance, and
      thereby photosensory capacity, rather than functioning as a signaling
      intermediate.

PMID- 18065692
TI  - Two distinct forms of M-locus protein kinase localize to the plasma membrane and
      interact directly with S-locus receptor kinase to transduce self-incompatibility
      signaling in Brassica rapa.
AB  - Many flowering plants possess systems of self-incompatibility (SI) to prevent
      inbreeding. In Brassica, SI recognition is controlled by the multiallelic gene
      complex (S-haplotypes) at the S-locus, which encodes both the male determinant S
      locus protein 11 (SP11/SCR) and the female determinant S-receptor kinase (SRK).
      Upon self-pollination, the S-haplotype-specific interaction between the pollen
      borne SP11 and the cognate stigmatic SRK receptor induces SI signaling in the
      stigmatic papilla cell and results in rejection of the self-pollen. Our genetic
      analysis of a self-compatible mutant revealed the involvement of a cytoplasmic
      protein kinase, M-locus protein kinase (MLPK), in the SI signaling, but its exact
      physiological function remains unknown. In this study, we identified two
      different MLPK transcripts, MLPKf1 and MLPKf2, which are produced using
      alternative transcriptional initiation sites and encode two isoforms that differ
      only at the N termini. While MLPKf1 and MLPKf2 exhibited distinct expression
      profiles, both were expressed in papilla cells. MLPKf1 localizes to the plasma
      membrane through its N-terminal myristoylation motif, while MLPKf2 localizes to
      the plasma membrane through its N-terminal hydrophobic region. Although both
      MLPKf1 and MLPKf2 could independently complement the mlpk/mlpk mutation, their
      mutant forms that lack the plasma membrane localization motifs failed to
      complement the mutation. Furthermore, a bimolecular fluorescence complementation
      assay revealed direct interactions between SRK and the MLPK isoforms in planta.
      These results suggest that MLPK isoforms localize to the papilla cell membrane
      and interact directly with SRK to transduce SI signaling.

PMID- 18065693
TI  - A nonsynonymous SNP in the ITGB3 gene disrupts the conserved membrane-proximal
      cytoplasmic salt bridge in the alphaIIbbeta3 integrin and cosegregates dominantly
      with abnormal proplatelet formation and macrothrombocytopenia.
AB  - We report a 3-generation pedigree with 5 individuals affected with a dominantly
      inherited macrothrombocytopenia. All 5 carry 2 nonsynonymous mutations resulting
      in a D723H mutation in the beta3 integrin and a P53L mutation in glycoprotein
      (GP) Ibalpha. We show that GPIbalpha-L53 is phenotypically silent, being also
      present in 3 unaffected pedigree members and in 7 of 1639 healthy controls. The
      beta3-H723 causes constitutive, albeit partial, activation of the alphaIIbbeta3
      complex by disruption of the highly conserved cytoplasmic salt bridge with
      arginine 995 in the alphaIIb integrin as evidenced by increased PAC-1 but not
      fibrinogen binding to the patients' resting platelets. This was confirmed in CHO
      alphaIIbbeta3-H723 transfectants, which also exhibited increased PAC-1 binding,
      increased adhesion to von Willebrand factor (VWF) in static conditions and to
      fibrinogen under shear stress. Crucially, we show that in the presence of
      fibrinogen, alphaIIbbeta3-H723, but not wild-type alphaIIbbeta3, generates a
      signal that leads to the formation of proplatelet-like protrusions in transfected
      CHO cells. Abnormal proplatelet formation was confirmed in the propositus's CD34+
      stem cell-derived megakaryocytes. We conclude that the constitutive activation of
      the alphaIIbbeta3-H723 receptor causes abnormal proplatelet formation, leading to
      incorrect sizing of platelets and the thrombocytopenia observed in the pedigree.

PMID- 18065694
TI  - Neuropilin-1 and neuropilin-2 act as coreceptors, potentiating proangiogenic
      activity.
AB  - Neuropilin-1 and -2 (NRP1 and NRP2) are the transmembrane glycoproteins
      interacting with 2 types of ligands: class III semaphorins and several members of
      the VEGF family, the main regulators of blood and lymphatic vessel growth. We
      show here that both NRP1 and NRP2 can also bind hepatocyte growth factor (HGF).
      HGF is a pleiotropic cytokine and potent proangiogenic molecule that acts on its
      target cells by binding to the c-met receptor. We found that the N-terminal
      domain of HGF is involved in the interaction with neuropilins. We demonstrated
      that invalidation of NRP1 or NRP2 by RNA interference in human umbilical vein
      endothelial cells (HUVECs) decreased HGF-induced c-met phosphorylation and VEGF
      A(165)- and HGF-mediated intracellular signaling. Accordingly, the disruption of
      NRP1 or NRP2 binding to VEGF-A(165) or HGF with a blocking antibody, decreased
      the proliferation and migration of endothelial cells. This effect may be further
      enhanced if VEGF-A(165) or HGF binding to both NRP1 and NRP2 was disrupted. Using
      a mouse Matrigel model, we demonstrated that NRP1 is essential for HGF-mediated
      angiogenesis in vivo. Our results suggest that, in endothelial cells, both NRP1
      and NRP2 function as proangiogenic coreceptors, potentiating the activity of at
      least 2 major proangiogenic cytokines, VEGF-A(165) and HGF.

PMID- 18065696
TI  - On our own terms.

PMID- 18065697
TI  - Experience of the area-based dullness method of cardiac percussion in the
      diagnosis of cardiorespiratory disorder.

PMID- 18065698
TI  - Proceedings of the royal society of medicine medical section 22 october 1907 Dr
      Gee, president of the section, in the chair.

PMID- 18065699
TI  - A contemporary reflection on Dr Gee's introduction to the first Medical Section
      meeting in 1907.

PMID- 18065700
TI  - Wernicke's encephalopathy in a funny patient.

PMID- 18065701
TI  - Drivers of violent conflict.

PMID- 18065702
TI  - Towards greener hospitals.

PMID- 18065703
TI  - Brain 'imaging' in the Renaissance.
AB  - During the Renaissance, a period of 'rebirth' for humanities and science, new
      knowledge and speculation began to emerge about the function of the human body,
      replacing ancient religious and philosophical dogma. The brain must have been a
      fascinating mystery to a Renaissance artist, but some speculation existed at that
      time on the function of its parts. Here we show how revived interest in anatomy
      and life sciences may have influenced the figurative work of Italian and Flemish
      masters, such as Rafael, Michelangelo and David. We present a historical
      perspective on the artists and the period in which they lived, their fascination
      for human anatomy and its symbolic use in their art. Prior to the 16th century,
      knowledge of the brain was limited and influenced in a dogmatic way by the
      teachings of Galen(1) who, as we now know, conducted his anatomical studies not
      on humans but on animals.(2) Nemesus, Bishop of Emesa, in around the year 400 was
      one of the first to attribute mental faculties to the brain, specifically to the
      ventricles. He identified two anterior (lateral) ventricles, to which he assigned
      perception, a middle ventricle responsible for cognition and a posterior
      ventricle for memory.(2,3) After a long period of stasis in the Middle Ages,
      Renaissance scholars realized the importance of making direct observations on
      dissected cadavers. Between 1504 and 1507, Leonardo da Vinci conducted
      experiments to reveal the anatomy of the ventricular system in the brain. He
      injected hot wax through a tube thrust into the ventricular cavities of an ox and
      then scraped the overlying brain off, thus obtaining, in a simple but ingenious
      way, an accurate cast of the ventricles.(2,4) Leonardo shared the belief promoted
      by scholarly Christians that the ventricles were the abode of rational soul. We
      have several examples of hidden symbolism in Renaissance paintings, but the
      influence of phrenology and this rudimentary knowledge of neuroanatomy on artists
      of that period is under-recognized. In the absence of documentary or scientific
      evidence as to the real intentions of these painters, the notion of such
      commixture of sacred and profane remains speculative and probably controversial,
      but at the same time fascinating and provocative. Here we present three examples
      of Renaissance masterpieces where such symbolism may have been used, although
      probably many more exist. Conducting an artistic, philosophical and anatomical
      analysis of the paintings can be an intriguing exercise, but the interpretation
      will inevitably be conjectural.

PMID- 18065704
TI  - William Osler and the jubjub of ethics; or how to teach medical ethics in the
      21st century.

PMID- 18065705
TI  - Assessment & management of sexual problems in women.

PMID- 18065706
TI  - Bufale spotting, part 8: assessing a letter to a journal.

PMID- 18065707
TI  - The Lazarus phenomenon.
AB  - Even though Lazarus phenomenon is rare, it is probably under reported. There is
      no doubt that Lazarus phenomenon is a reality but so far the scientific
      explanations have been inadequate. So far the only plausible explanation at least
      in some cases is auto-PEEP and impaired venous return. In patients with PEA or
      asystole, dynamic hyperinflation should considered as a cause and a short period
      of apnoea (30-60 seconds) should be tried before stopping resuscitation. Since
      ROSC occurred within 10 minutes in most cases, patients should be passively
      monitored for at least 10 minutes after the cessation of CPR before confirming
      death.

PMID- 18065708
TI  - The use of orchids in Chinese medicine.
AB  - In this article, the therapeutic uses of five Chinese medicines that contain
      orchids are discussed, together with a brief report of some of the animal
      experimentation undertaken. The impression that these preparations have no
      therapeutic use may be incorrect. However, herbal preparations have not usually
      been subject to the rigorous characterization and standardization necessary for
      clinical study, and persuading practitioners that substances in use for many
      centuries still need to be tested in randomized controlled clinical trials is
      proving a significant challenge.

PMID- 18065709
TI  - First do no harm: the impact of recent armed conflict on maternal and child
      health in Sub-Saharan Africa.
AB  - OBJECTIVES: To compare the rates of under-5 mortality, malnutrition, maternal
      mortality and other factors which influence health in countries with and without
      recent conflict. To compare central government expenditure on defence, education
      and health in countries with and without recent conflict. To summarize the amount
      spent on SALW and the main legal suppliers to countries in Sub-Saharan African
      countries (SSA), and to summarize licensed production of Small Arms and Light
      Weapons (SALW) in these countries. DESIGN: We compared the under-5 mortality rate
      in 2004 and the adjusted maternal mortality ratio in SSA which have and have not
      experienced recent armed conflict (post-1990). We also compared the percentage of
      children who are underweight in both sets of countries, and expenditure on
      defence, health and education. SETTING: Demographic data and central government
      expenditure details (1994-2004) were taken from UNICEF's The State of the World's
      Children 2006 report. MAIN OUTCOME MEASURES: Under-5 mortality, adjusted maternal
      mortality, and government expenditure. RESULTS: 21 countries have and 21
      countries have not experienced recent conflict in this dataset of 42 countries in
      SSA. Median under-5 mortality in countries with recent conflict is 197/1000 live
      births, versus 137/1000 live births in countries without recent conflict. In
      countries which have experienced recent conflict, a median of 27% of under-5s
      were moderately underweight, versus 22% in countries without recent conflict. The
      median adjusted maternal mortality in countries with recent conflict was
      1000/100,000 births versus 690/100,000 births in countries without recent
      conflict. Median reported maternal mortality ratio is also significantly higher
      in countries with recent conflict. Expenditure on health and education is
      significantly lower and expenditure on defence significantly higher if there has
      been recent conflict. CONCLUSIONS: There appears to be an association between
      recent conflict and higher rates of under-5 mortality, malnutrition and maternal
      mortality. Governments spend more on defence and less on health and education if
      there has been a recent conflict. SALW are the main weapon used and France and
      the UK appear to be the two main suppliers of SALW to SSA.

PMID- 18065710
TI  - Yes Sir, no Sir, not much difference Sir.
AB  - OBJECTIVE: To assess whether making the sender's knighthood explicit in a series
      of letters would have any detectable effect on the response. DESIGN: A random
      sequence was generated by flipping a coin to determine whether a letter would
      have 'Sir Iain Chalmers' or 'Iain Chalmers' typed under the signature. This
      sequence was prepared independently of the preparation of an alphabetic list of
      the intended recipients and was then used to determine which letter would be
      sent. The allocation could not be influenced by prior knowledge of the recipient.
      Two batches of letters were sent. SETTING: Medical royal colleges and associated
      faculties, and postgraduate medical and dental schools in the UK. PARTICIPANTS:
      Presidents and deans of medical royal colleges and deans of postgraduate medical
      and dental schools in the UK. MAIN OUTCOME MEASURES: Rates of response and the
      mean number of days between the posting of the original letter and the date on
      the response. RESULTS: No differences between the groups were detected in the
      response rates: 91% and 90% for 'Sir Iain Chalmers' and 'Iain Chalmers' (relative
      rate for response of 1.01, 95%CI 0.83-1.23, P = 0.92), or in the mean number of
      days to response ('Sir': 32 days; 'no Sir': 33 days). CONCLUSIONS: This finding
      is consistent with a systematic review of responses to postal surveys, in which
      the effect of the status of the signatory was investigated. Combining our result
      with the two trials that are most comparable to our study, in which letters from
      professors were compared with letters from students, gives a relative response
      rate of 1.00 (95% CI 0.91-1.10, P = 0.99). There is, therefore, no evidence from
      the existing randomized experiments that the status of the signatory has any
      impact on the likelihood or promptness of response-even if the status was
      conferred by the British monarch.

PMID- 18065711
TI  - Takotsubo cardiomyopathy.

PMID- 18065712
TI  - An historical perspective on meta-analysis: dealing quantitatively with varying
      study results.

PMID- 18065713
TI  - Brave new world: a reflection on the life's work of John Fry and its link to
      General Practice in the 21st century.

PMID- 18065714
TI  - Faithful editing of a tomato-specific mRNA editing site in transgenic tobacco
      chloroplasts.
AB  - RNA editing sites and their site-specific trans-acting recognition factors are
      thought to have coevolved. Hence, evolutionary loss of an editing site by a
      genomic mutation is normally followed by the loss of the specific recognition
      factor for this site, due to the absence of selective pressure for its
      maintenance. Here, we have tested this scenario for the only tomato-specific
      plastid RNA editing site. A single C-to-U editing site in the tomato rps12 gene
      is absent from the tobacco and nightshade plastid genomes, where the presence of
      a genomic T nucleotide obviates the need for editing of the rps12 mRNA. We have
      introduced the tomato editing site into the tobacco rps12 gene by plastid
      transformation and find that, surprisingly, this heterologous site is efficiently
      edited in the transplastomic plants. This suggests that the trans-acting
      recognition factor for the rps12 editing site has been maintained, presumably
      because it serves another function in tobacco plastids. Bioinformatics analyses
      identified an editing site in the rpoB gene of tobacco and tomato whose sequence
      context exhibits striking similarity to that of the tomato rps12 editing site.
      This may suggest that requirement for rpoB editing resulted in maintenance of the
      rps12 editing activity or, alternatively, the pre-existing rpoB editing activity
      facilitated the evolution of a novel editing site in rps12.

PMID- 18065715
TI  - Modulating alternative splicing by cotranscriptional cleavage of nascent intronic
      RNA.
AB  - Cotranscriptional cleavage mediated by a hammerhead ribozyme can affect
      alternative splicing if interposed between an exon and its intronic regulatory
      elements. This has been demonstrated using two different alternative splicing
      systems based on alpha-tropomyosin and fibronectin genes. We suggest that there
      is a requirement for intronic regulatory elements to be covalently attached to
      exons that are in turn tethered to the elongating polymerase. In the case of the
      alternatively spliced EDA exon of the fibronectin gene, we demonstrate that the
      newly identified intronic downstream regulatory element is associated with the
      splicing regulatory protein SRp20. Our results suggest that targeted hammerhead
      ribozyme cleavage within introns can be used as a tool to define splicing
      regulatory elements.

PMID- 18065716
TI  - KREPA6 is an RNA-binding protein essential for editosome integrity and survival
      of Trypanosoma brucei.
AB  - Most mitochondrial mRNAs in kinetoplastid protozoa require post-transcriptional
      RNA editing that inserts and deletes uridylates, a process that is catalyzed by
      multiprotein editosomes. KREPA6 is the smallest of six editosome proteins that
      have predicted oligonucleotide-binding (OB) folds. Inactivation of KREPA6
      expression results in disruption and ultimate loss of approximately 20S
      editosomes and inhibition of procyclic form cell growth. Gel shift studies show
      that recombinant KREPA6 binds RNA, but not DNA, with a preference for oligo-(U)
      whether on the 3' end of gRNA or as a (UU)(12) homopolymer. Thus, KREPA6 is
      essential for the structural integrity and presence of approximately 20S
      editosomes and for cell viability. It functions in RNA binding perhaps primarily
      through the gRNA 3' oligo(U) tail. The significance of these findings to key
      steps in editing is discussed.

PMID- 18065717
TI  - Yeast as a model of human mitochondrial tRNA base substitutions: investigation of
      the molecular basis of respiratory defects.
AB  - We investigate the relationships between acylation defects and structure
      alterations due to base substitutions in yeast mitochondrial (mt) tRNA(UUR)(Leu).
      The studied substitutions are equivalent to the A3243G and T3250C human
      pathogenetic tRNA mutations. Our data show that both mutations can produce
      tRNA(UUR)(Leu) acylation defects, although to a different extent. For mutant A14G
      (equivalent to MELAS A3243G base substitution), the presence of the tRNA and its
      defective aminoacylation could be observed only in the nuclear context of W303, a
      strain where the protein synthesis defects caused by tRNA base substitutions are
      far less severe than in previously studied strains. For mutant T20C (equivalent
      to the MM/CPEO human T3250C mutation), the acylation defect was less severe, and
      a thermosensitive acylation could be detected also in the MCC123 strain. The
      correlation between the severity of the in vivo phenotypes of yeast tRNA mutants
      and those obtained in in vitro studies of human tRNA mutants supports the view
      that yeast is a suitable model to study the cellular and molecular effects of
      tRNA mutations involved in human pathologies. Furthermore, the yeast model offers
      the possibility of modulating the severity of yeast respiratory phenotypes by
      studying the tRNA mutants in different nuclear contexts. The nucleotides at
      positions 14 and 20 are both highly conserved in yeast and human mt tRNAs;
      however, the different effect of their mutations can be explained by structure
      analyses and quantum mechanics calculations that can shed light on the molecular
      mechanisms responsible for the experimentally determined defects of the mutants.

PMID- 18065718
TI  - A simple ligation-based method to increase the information density in sequencing
      reactions used to deconvolute nucleic acid selections.
AB  - Herein, a method is described to increase the information density of sequencing
      experiments used to deconvolute nucleic acid selections. The method is facile and
      should be applicable to any selection experiment. A critical feature of this
      method is the use of biotinylated primers to amplify and encode a BamHI
      restriction site on both ends of a PCR product. After amplification, the PCR
      reaction is captured onto streptavidin resin, washed, and digested directly on
      the resin. Resin-based digestion affords clean product that is devoid of
      partially digested products and unincorporated PCR primers. The product's
      complementary ends are annealed and ligated together with T4 DNA ligase. Analysis
      of ligation products shows formation of concatemers of different length and
      little detectable monomer. Sequencing results produced data that routinely
      contained three to four copies of the library. This method allows for more
      efficient formulation of structure-activity relationships since multiple active
      sequences are identified from a single clone.

PMID- 18065719
TI  - Selective activation of medial prefrontal-to-accumbens projection neurons by
      amygdala stimulation and Pavlovian conditioned stimuli.
AB  - Medial prefrontal cortex (mPFC) neurons respond to Pavlovian conditioned stimuli,
      and these responses depend on input from the basolateral amygdala (BLA). In this
      study, we examined the mPFC efferent circuits mediating conditioned responding by
      testing whether specific subsets of mPFC projection neurons receive BLA input and
      respond to conditioned stimuli. In urethane-anesthetized rats, we identified mPFC
      neurons that projected to the nucleus accumbens (NAcc) or to the contralateral
      mPFC (cmPFC) using antidromic activation. Stimulation of the BLA and Pavlovian
      conditioned odors selectively activated a subpopulation of ventral mPFC neurons
      that projected to NAcc, but elicited virtually no activation in mPFC neurons that
      projected to cmPFC. BLA stimulation typically evoked inhibitory responses among
      nonactivated neurons projecting to either site. These results suggest that the
      ventral mPFC-to-NAcc pathway may support behavioral responses to conditioned
      cues. Furthermore, because projections from the BLA (which also encode affective
      information) and the mPFC converge within the NAcc, the BLA may recruit the mPFC
      to drive specific sets of NAcc neurons, and thereby exert control over prefrontal
      cortical-striato-thalamocortical information flow.

PMID- 18065720
TI  - Stimulus-dependent interaction between the visual areas 17 and 18 of the 2
      hemispheres of the ferret (Mustela putorius).
AB  - To study how the visual areas of the 2 hemispheres interact in processing visual
      stimuli we have recorded local field potentials in the callosally connected parts
      of areas 17 and 18 of the ferret during the presentation of 3 kinds of stimuli:
      2.5 degrees squares flashed for 50 ms randomly in the visual field (S1), 4 full
      field gratings differing in orientation by 45 degrees and identical in the 2
      hemifields (S2) and gratings as above but whose orientation and/or direction of
      motion differed by 90 degrees in the 2 hemifields (S3). The gratings remained
      stationary for 0.5 s and then moved in 1 of the 2 directions perpendicular to
      their orientation for 3 s. We compared the responses in baseline conditions with
      those obtained whereas the contralateral visual areas were inactivated by
      cooling. Cooling did not affect the responses to S1 but it modified those to S2
      and to S3 generally increasing early components of the response while decreasing
      later components. These findings indicate that interhemispheric processing is
      restricted to visual stimuli which achieve spatial summation and that it involves
      complex inhibitory and facilitatory effects, possibly carried out by
      interhemispheric pathways of different conduction velocity.

PMID- 18065721
TI  - Dynamic properties of the representation of the visual field midline in the
      visual areas 17 and 18 of the ferret (Mustela putorius).
AB  - In mammals, the visual field is split along the midline, each hemisphere
      representing the contralateral hemifield. We determined that, in the ferret, an 8
      to 10-deg-wide strip of visual field near the midline is represented in both
      hemispheres. Bright squares (1.5 deg) were flashed at different azimuths within
      the central 20 deg of the visual field. Stimuli were flashed either alone or
      sequentially, and the responses were analyzed with the voltage-sensitive dye
      (VSD) RH 795 and/or by recording local field potentials (LFPs). In both VSD and
      LFP experiments, each stimulus evoked a cortical response field that extended
      over visual areas 17 and 18 up to a surface of 1-1.5 mm(2) and then shrank again.
      Amplitude of the responses decreased approaching the visual midline and the
      latency increased. These positional differences are likely to originate from the
      spatiotemporal structure of the peripheral response fields (PRFs) that form a
      mosaic in areas 17 and 18, interrupted near the visual midline. Unexpectedly,
      interhemispheric connections appear not to modify these PRFs' effects and may not
      contribute to the responses to discrete, flashed stimuli.

PMID- 18065722
TI  - Paying attention to social meaning: an FMRI study.
AB  - Animations of simple geometric shapes are readily interpreted as animate agents
      engaged in meaningful social interactions. Such animations have been shown to
      activate brain regions implicated in the detection of animate motion, in
      understanding the intentions of others as well as areas commonly linked to the
      processing of social and emotional information. However, attribution of animacy
      does not occur under all circumstances and the precise conditions under which
      specific regions are activated remains unclear. In a functional magnetic
      resonance imaging study we manipulated viewers' perspective to assess the part
      played by selective attention. Participants were cued to attend either to spatial
      properties of the movements or to the kind of social behavior it could represent.
      Activations that occurred to the initial cue, while observing the animations
      themselves and while responding to a postpresentation probe, were analyzed
      separately. Results showed that activity in the social brain network was strongly
      influenced by selective attention, and that remarkably similar activations were
      seen during film viewing and in response to probe questions. Our use of stimuli
      supporting rich and diverse social narratives likely enhanced the influence of
      top-down processes on neural activity in the social brain.

PMID- 18065723
TI  - Foxg1 haploinsufficiency reduces the population of cortical intermediate
      progenitor cells: effect of increased p21 expression.
AB  - Foxg1 is a transcription factor that is critical for forebrain development.
      Foxg1(+/Cre) mice were used to test the hypotheses 1) that the subventricular
      zone (SZ) generates supragranular neurons, 2) that Foxg1-regulated activities
      define the output from the SZ, and 3) that Foxg1 is involved in the suppression
      of p21-initiated cell-cycle exit. Foxg1(+/Cre) mice have thinner neocortices than
      wild-type controls, specifically in the supragranular layers, as detected by Brn2
      immunostaining. Cell proliferation in the ventricular zone (VZ) and SZ was
      examined to investigate the reduction in upper layer neurons. The number of
      cycling VZ cells was similar in Foxg1(+/+) and Foxg1(+/Cre) brains.
      Interestingly, cell proliferation in the SZ and intermediate progenitor cell
      (IPC) production (noted by Tbr2-immunostaining) was reduced in Foxg1(+/Cre)
      brains. These decreases coincided with increased expression of the cell-cycle
      inhibitor p21 in the VZ and SZ. Furthermore, colocalization of p21 with markers
      of cell proliferation and IPCs indicated that p21 was temporally expressed to
      influence the proliferative fate of IPCs. Thus, the present data are consistent
      with the above hypotheses, particularly, that during corticogenesis, Foxg1
      regulated activities enable the expansion of the IPC population likely through
      suppression of p21-dependent cell-cycle exit.

PMID- 18065724
TI  - Influence of TCDD and natural Ah receptor agonists on benzo[a]pyrene-DNA adduct
      formation in the Caco-2 human colon cell line.
AB  - Several compounds originating from cruciferous vegetables and citrus fruits bind
      to and activate the aryl hydrocarbon receptor (AhR). This receptor plays an
      important role in the toxicity of the known tumour promoter and potent AhR
      agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, vegetables and
      fruits are generally considered as healthy. Therefore, besides the AhR
      activation, the natural AhR agonists (NAhRAs) are assumed to show other health
      concerning effects. AhR activation induces several cytochrome P450 phase I
      enzymes involved, e.g. in the bioactivation of carcinogenic polycyclic aromatic
      hydrocarbons, like benzo[a]pyrene (BaP), and may as such stimulate DNA adduct
      formation of those compounds. Therefore, the influence of TCDD, indolo[3,2
      b]carbazole (ICZ, an NAhRA originating from cruciferous vegetables) and an NAhRA
      containing extract of grapefruit juice (GJE) on BaP-DNA adduct formation in the
      human Caco-2 cell line was studied. Also, we investigated if different effects of
      TCDD, ICZ and GJE on adduct formation could be related to the modulation of
      transcription of biotransformation- and DNA-repair enzymes. Co-exposure to high
      AhR-activating concentrations of both TCDD and ICZ significantly reduced the
      amount of BaP-DNA adducts at 0.1 microM BaP, while at higher concentrations of
      BaP no influence was observed. In contrast, exposure to 0.1 microM BaP combined
      with GJE showed a significant increase in BaP-DNA adducts, and a significant
      decrease at 0.3 and 1 microM BaP. These differences could not be related to
      transcription of the phase I and II enzymes CYP1A1, CYP1B1, NQO1, GSTP1 and
      UGT1A6 or to transcription of the nucleotide excision repair enzymes ERCC1, XPA,
      XPC, XPF and XPG. We conclude that ICZ showed a similar effect on BaP-DNA adduct
      formation than TCDD, while GJE influenced the adduct formation in a different
      way. The difference in the influence on adduct formation may be due to effects at
      the level of enzyme activity, rather than gene expression.

PMID- 18065725
TI  - Genetic variants of glutathione S-transferase as possible risk factors for
      hepatocellular carcinoma: a HuGE systematic review and meta-analysis.
AB  - The authors performed a systematic review and meta-analysis to determine the
      effect of polymorphisms in genes encoding glutathione S-transferases (GSTs),
      phase II isoenzymes involved in cellular detoxification, on risk of
      hepatocellular carcinoma (HCC). Fifteen eligible studies were identified: 14
      evaluated GSTM1; 13, GSTT1; three, GSTP1; and one each evaluated GSTM2, GSTM3,
      GSTA1, GSTA4, GSTO1, and GSTO2, respectively. All were case-control studies
      performed in populations with high (Asian, African) and medium (European) HCC
      incidence rates. Random-effects meta-analyses suggested a small excess risk of
      HCC with GSTT1 null (odds ratio (OR) = 1.19, 95% confidence interval (CI): 0.99,
      1.44) and possibly GSTM1 null (OR = 1.16, 95% CI: 0.89, 1.53) genotypes.
      Cumulative meta-analyses demonstrated that both pooled estimators generally
      trended toward a small excess risk with publication of more recent studies.
      Results for GSTP1 A313G suggested no excess risk (OR = 0.75, 95% CI: 0.50, 1.15).
      A number of potentially interesting gene-gene and gene-environment interactions
      were reported, but these were too few and inconsistent to allow meta-analysis.
      The overall results suggest that there may be a small excess risk of HCC in
      individuals with GSTT1 null and possibly also with GSTM1 null genotypes. However,
      given the relatively limited total number of subjects examined and observed
      between-study heterogeneity, chance could not be excluded.

PMID- 18065726
TI  - Flash points.

PMID- 18065727
TI  - Optimal management of retroperitoneal metastatic nonseminomatous testicular
      cancer: toward a better selection between scalpel and needle.

PMID- 18065728
TI  - Three-gene prognostic classifier for early-stage non small-cell lung cancer.
AB  - PURPOSE: Several microarray studies have reported gene expression signatures that
      classify non-small-cell lung carcinoma (NSCLC) patients into different prognostic
      groups. However, the prognostic gene lists reported to date overlap poorly across
      studies, and few have been validated independently using more quantitative assay
      methods. PATIENTS AND METHODS: The expression of 158 putative prognostic genes
      identified in previous microarray studies was analyzed by reverse transcription
      quantitative polymerase chain reaction in the tumors of 147 NSCLC patients.
      Concordance indices and risk scores were used to identify a stage-independent set
      of genes that could classify patients with significantly different prognoses.
      RESULTS: We have identified a three-gene classifier (STX1A, HIF1A, and CCR7) for
      overall survival (hazard ratio = 3.8; 95% CI, 1.7 to 8.2; P < .001). The
      classifier was also able to stratify stage I and II patients and further improved
      the predictive ability of clinical factors such as histology and tumor stage. The
      predictive value of this three-gene classifier was validated in two large
      independent microarray data sets from Harvard and Duke Universities. CONCLUSION:
      We have identified a new three-gene classifier that is independent of and
      improves on stage to stratify early-stage NSCLC patients with significantly
      different prognoses. This classifier may be tested further for its potential
      value to improve the selection of resected NSCLC patients in adjuvant therapy.

PMID- 18065729
TI  - Lung cancer in elderly patients: an analysis of the surveillance, epidemiology,
      and end results database.
AB  - PURPOSE: To study the burden and outcome of lung cancer in the elderly,
      particularly for patients aged 80 years and older. PATIENTS AND METHODS: The
      national Surveillance, Epidemiology, and End Results database was analyzed for
      lung cancer outcomes during the period 1988 to 2003. A comparison was carried out
      between patients with lung cancer 80 years and older, 70 to 79 years, and younger
      than 70 years for demographics; stage distribution; 5-year relative survival; and
      survival based on histology, sex, race, stage, and treatment. The temporal trends
      in survival during the years 1988 to 1997 and 1998 to 2003 were also analyzed.
      RESULTS: Of 316,682 patients eligible for the analysis, 45,912 (14%) were 80
      years or older (ie, very elderly); 103,963 (33%) were 70 to 79 years; and 166,807
      (53%) were younger than 70 years. The distribution by stage and histology was
      comparable for all the three groups. Overall survival rate at 5 years was lower
      in the very elderly (7.4% v 12.3% v 15.5%; P < .0001) across sex, histologic
      subtypes, stages, and racial categories. Patients aged 80 years or older were
      less likely to receive local therapy (no surgery or radiation) than younger
      patients (47% v 28% and 19% for the age subgroups >/= 80 years, 70 to 79 years,
      and < 70 years, respectively). Overall outcomes for patients who underwent
      surgical therapy or radiation were comparable across the three age groups. In
      general, survival outcomes for the subgroup aged 70 to 79 years were similar to
      those of the subgroup aged 80 years and older who received single modality local
      therapy. CONCLUSION: Patients 80 years or older account for 14% (70 years or
      older accounted for 47%) of all lung cancers, are less likely to be subjected to
      surgery or radiation, and have inferior outcomes when compared with younger
      patients.

PMID- 18065730
TI  - Panel of serum biomarkers for the diagnosis of lung cancer.
AB  - PURPOSE: Currently, a blood test for lung cancer does not exist. Serum biomarkers
      that could aid clinicians in making case management decisions would be enormously
      valuable. We used two proteomic platforms and a literature search to select
      candidate serum markers for the diagnosis of lung cancer. METHODS: We initially
      assayed six serum proteins, four discovered by proteomics and two previously
      known to be cancer associated, on a training set of sera from 100 patients (50
      with a new diagnosis of lung cancer and 50 age- and sex-matched controls).
      Classification and Regression Tree (CART) analysis selected a panel of four
      markers that most efficiently predicted which patients had lung cancer. An
      independent, blinded validation set of sera from 97 patients (49 lung cancer
      patients and 48 matched controls) determined the accuracy of the four markers to
      predict which patients had lung cancer. RESULTS: Four serum proteins
      carcinoembryonic antigen, retinol binding protein, alpha1-antitrypsin, and
      squamous cell carcinoma antigen-were collectively found to correctly classify the
      majority of lung cancer and control patients in the training set (sensitivity,
      89.3%; specificity, 84.7%). These markers also accurately classified patients in
      the independent validation set (sensitivity, 77.8%; specificity, 75.4%).
      Remarkably, 90% of patients who fell into any one of three groupings in the CART
      analysis had lung cancer. CONCLUSION: This panel of four serum proteins is
      valuable in suggesting the diagnosis of lung cancer. These data may be useful for
      treating patients with an indeterminate pulmonary lesion, and potentially in
      predicting individuals at high risk for lung cancer.

PMID- 18065731
TI  - Randomized, controlled trial of acupuncture for the treatment of hot flashes in
      breast cancer patients.
AB  - PURPOSE: To determine the immediate and long-term effects of true acupuncture
      versus sham acupuncture on hot flash frequency in women with breast cancer.
      PATIENTS AND METHODS: Seventy-two women with breast cancer experiencing three or
      more hot flashes per day were randomly assigned to receive either true or sham
      acupuncture. Interventions were given twice weekly for 4 consecutive weeks. Hot
      flash frequency was evaluated at baseline, at 6 weeks, and at 6 months after
      initiation of treatment. Patients initially randomly assigned to the sham group
      were crossed over to true acupuncture starting at week 7. RESULTS: The mean
      number of hot flashes per day was reduced from 8.7 (standard deviation [SD], 3.9)
      to 6.2 (SD, 4.2) in the true acupuncture group and from 10.0 (SD, 6.1) to 7.6
      (SD, 5.7) in the sham group. True acupuncture was associated with 0.8 fewer hot
      flashes per day than sham at 6 weeks, but the difference did not reach
      statistical significance (95% CI, -0.7 to 2.4; P = .3). When participants in the
      sham acupuncture group were crossed over to true acupuncture, a further reduction
      in the frequency of hot flashes was seen. This reduction in hot flash frequency
      persisted for up to 6 months after the completion of treatment. CONCLUSION: Hot
      flash frequency in breast cancer patients was reduced following acupuncture.
      However, when compared with sham acupuncture, the reduction by the acupuncture
      regimen as provided in the current study did not reach statistical significance.
      We cannot exclude the possibility that a longer and more intense acupuncture
      intervention could produce a larger reduction of these symptoms.

PMID- 18065732
TI  - Nonrandomized comparison of primary chemotherapy and retroperitoneal lymph node
      dissection for clinical stage IIA and IIB nonseminomatous germ cell testicular
      cancer.
AB  - PURPOSE Patients with clinical stage (CS) IIA and IIB nonseminomatous germ cell
      tumor (NSGCT) with adenopathy more than 2 cm, multiple masses, elevated serum
      tumor markers, or disease outside the primary landing zone have increasingly been
      recommended to receive primary chemotherapy over time at our institution. The
      impact of these selection factors on the outcome of patients managed primarily by
      retroperitoneal lymph node dissection (RPLND) or chemotherapy was examined.
      PATIENTS AND METHODS Between 1989 and 2002, 252 patients with CS IIA and IIB
      NSGCT were referred to our institution for initial management, of whom 136
      underwent RPLND and 116 received chemotherapy and postchemotherapy RPLND. Patient
      information was obtained from a prospective RPLND database. Results
      Proportionately more patients received chemotherapy over time (22% in 1989 to
      1993 v 68% in 1999 to 2002), and the relapse-free survival (RFS) subsequently
      improved from 84% (1989 to 1998) to 98% (1999 to 2002; P = .004) without
      increasing the proportion who received any chemotherapy (70% v 79%; P = .16). By
      increasingly selecting patients with adverse features for primary chemotherapy,
      the RFS after RPLND improved from 78% to 100% (P = .019), but rates of pathologic
      stage II and retroperitoneal teratoma were unaffected. Retroperitoneal histology
      and RFS did not change over time for chemotherapy patients. Primary chemotherapy
      was associated with improved RFS compared with RPLND (98% v 79%; P < .001), but
      disease-specific survival did not differ significantly (100% v 98%; P = .3).
      CONCLUSION Patient selection factors have significantly improved the outcome of
      patients with CS IIA and IIB NSGCT without substantially increasing the
      proportion of patients exposed to chemotherapy.

PMID- 18065733
TI  - Determining prognosis in patients with pancreatic endocrine neoplasms: can the
      WHO classification system be simplified?
AB  - PURPOSE: The WHO classification for well-differentiated pancreatic endocrine
      neoplasms (PENs) incorporates both stage and grade. This study compares the
      prognostic value of a simplified staging and grading system with the WHO system
      in a large single-institution study. PATIENTS AND METHODS: A prospective database
      (1982 to 2005) identified 183 patients who underwent operative treatment for
      PENs. Tumors were staged (< 2 cm primary, >/= 2 cm primary, or metastases) and
      graded (low grade: no necrosis and < two mitoses/50 high-powered fields [HPF]; or
      intermediate grade: necrosis and/or >/= two mitoses/50 HPF) with a simplified
      schema. Influence of stage and grade on recurrence and disease-specific survival
      (DSS) was determined. Prognostic strength was assessed with the concordance index
      (CI). RESULTS: Median age of the 183 patients was 56 years, and 53% were women.
      Median follow-up time was 44 months (range, 1 to 226 months). Classification
      identified 28 patients (15%) with WHO 1.1 disease, 74 (41%) with 1.2 disease, and
      81 (44%) with 2.0 disease. Classification by stage identified 35 patients (19%)
      with tumors less than 2 cm, 96 (52%) with tumors >/= 2 cm, and 52 (29%) with
      nodal or distant metastases. Tumors were low grade in 102 patients (56%). Earlier
      stage tumors were more likely to be low grade (< 2 cm, 83%; >/= 2 cm, 61%;
      metastases, 28%; P < .001). The WHO classification, tumor stage, and grade were
      associated with 5-year DSS (P < .001). Tumors >/= 2 cm or metastases are
      stratified by grade (5-year DSS rate for low v intermediate grade: >/= 2 cm, 97%
      v 80%, respectively; P < .001; metastases, 93% v 62%, respectively; P = .05). The
      CI was 0.72 for WHO, 0.71 for stage, 0.66 for grade, and 0.76 for stage combined
      with grade. CONCLUSION: Accurate prognostic information can be obtained by
      combining tumor size and metastases with simple grading information based on
      necrosis and mitotic rate.

PMID- 18065734
TI  - Hope and prognostic disclosure.
AB  - PURPOSE: Physicians sometimes selectively convey prognostic information to
      support patients' hopes. However, the relationship between prognostic disclosure
      and hope is not known. PATIENTS AND METHODS: We surveyed 194 parents of children
      with cancer (overall response rate, 70%) in their first year of treatment at the
      Dana-Farber Cancer Institute and Children's Hospital (Boston, MA), and we
      surveyed the children's physicians. We evaluated relationships between parental
      recall of prognostic disclosure by the physician and possible outcomes, including
      hope, trust, and emotional distress. Our main outcome was assessed by asking
      parents how often the way the child's oncologist communicated with them about the
      children's cancers made them feel hopeful. RESULTS: Nearly half of parents
      reported that physician communication always made them feel hopeful. Parents who
      reported receiving a greater number of elements of prognostic disclosure were
      more likely to report communication-related hope (odds ratio [OR], 1.77 per
      element of disclosure; P = .001), even when the likelihood of a cure was low (OR,
      5.98 per element of disclosure with likelihood of a cure < 25%; P = .03). In a
      multivariable model, parents were more likely to report that physician
      communication always made them feel hopeful when they also reported receipt of
      more elements of prognostic disclosure (OR, 1.60; P = .03) and high-quality
      communication (OR, 6.58; P < .0001). Communication-related hope was inversely
      associated with the child's likelihood of cure (OR, 0.65; P = .005). CONCLUSION:
      Although physicians sometimes limit prognostic information to preserve hope, we
      found no evidence that prognostic disclosure makes parents less hopeful. Instead,
      disclosure of prognosis by the physician can support hope, even when the
      prognosis is poor.

PMID- 18065735
TI  - Outcomes after hematopoietic stem-cell transplantation for hematologic
      malignancies in patients with or without advance care planning.
AB  - PURPOSE: Engagement in advance care planning (ACP) is viewed as a way to prepare
      for possible death. In patients undergoing hematopoietic stem-cell
      transplantation (HSCT), an aggressive but possibly curative procedure for cancer,
      encouraging engagement in ACP is difficult. We conducted this analysis to
      determine if engagement in ACP among patients who undergo HSCT is associated with
      adverse outcomes. PATIENTS AND METHODS: Adult patients who were undergoing their
      first HSCT for hematologic malignancies between 2001 and 2003 were included. ACP
      was defined as having a living will, a power of attorney for health care, or life
      support instructions. Outcomes assessed included the length of hospital stay, in
      hospital mortality, and overall survival. RESULTS: Of the 343 patients, 172 did
      not have ACP, whereas 171 did have ACP, and 127 of those were reviewable. Of
      those with reviewable ACP, 28 patients (22%) completed ACP before cancer
      diagnosis, 87 (68%) completed ACP after the cancer diagnosis but before HSCT, and
      12 (10%) engaged in ACP after HSCT. Patients without ACP before HSCT had a
      significantly greater risk of death compared with patients with ACP (hazard
      ratio, 2.11; 95% CI, 1.34 to 3.33; P = .001) while adjusting for statistically
      significant factors. CONCLUSION: Our study demonstrated that lack of engagement
      in ACP is associated with adverse outcomes after HSCT. Thus, the patients least
      likely to have planned for poor outcomes are the ones most likely to face them.
      Additional studies should evaluate the nature of this association and should seek
      modifiable explanatory factors that could be the target of interventions.

PMID- 18065736
TI  - Meta-analysis of hepatic arterial infusion for unresectable liver metastases from
      colorectal cancer: the end of an era?
AB  - PURPOSE: The treatment of unresectable liver-confined metastatic disease from
      colorectal cancer (CRC) is a challenging issue. Although locoregional treatments
      such as hepatic arterial infusion (HAI) claim the advantage of delivering higher
      doses of anticancer agents directly into the affected organ, the benefit in terms
      of overall survival (OS) is unclear. We quantitatively summarized the results of
      randomized controlled trials (RCT) comparing HAI with systemic chemotherapy
      (SCT). METHODS: To date, 10 RCTs have been published, for a total of 1,277
      patients enrolled. For tumor response rates, relative risks (RR) and their 95%
      CIs were obtained from raw data; for OS, hazard ratios (HRs) and their 95% CIs
      were extrapolated from the Kaplan-Meier survival curves. RESULTS: HAI regimens
      were based on floxuridine (FUDR) in nine of 10 RCTs, whereas in one RCT,
      fluorouracil (FU) + leucovorin was used. SCT consisted of FUDR, FU, FU +
      leucovorin, or a miscellany of FU and best supportive care in three, one, four,
      and two studies, respectively. Pooling the data, tumor response rate was 42.9%
      and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P <
      .0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT,
      respectively; the meta-risk of death was not statistically different between the
      two study groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = .24). CONCLUSION:
      Currently available evidence does not support the clinical or investigational use
      of fluoropyrimidine-based HAI alone for the treatment of patients with
      unresectable CRC liver metastases, at least as a first-line therapy.

PMID- 18065737
TI  - Axillary apocrine carcinoma with brain metastases.

PMID- 18065738
TI  - Detection of early-stage ovarian cancer by FDG-PET-CT in a patient with BRCA2
      positive breast cancer.

PMID- 18065739
TI  - Mycosis fungoides with leptomeningeal involvement.

PMID- 18065740
TI  - Use of trastuzumab for metastatic breast cancer in Australia: inaccurate results
      and alternative interpretation of findings.

PMID- 18065742
TI  - Does psychotherapy affect the survival of cancer patients? More questions than
      answers.

PMID- 18065743
TI  - Value and use of economic evaluation in oncology.

PMID- 18065744
TI  - Magnetic resonance imaging in predicting pathological response of triple negative
      breast cancer following neoadjuvant chemotherapy.

PMID- 18065745
TI  - Validation of a new prognostic index for advanced epithelial ovarian cancer:
      results from its application to a UK-based cohort.

PMID- 18065746
TI  - Adjuvant radiotherapy after surgery for pathologically advanced prostate cancer.

PMID- 18065747
TI  - Are prostate-specific antigen changes valid surrogates for survival in hormone
      refractory prostate cancer? A meta-analysis is needed!

PMID- 18065748
TI  - In response to "Drug metabolizing enzyme polymorphisms predict clinical outcome
      in a node-positive breast cancer cohort".

PMID- 18065749
TI  - Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily enzyme
      CYP4F11.
AB  - Long-chain 3-hydroxydicarboxylic acids (3-OHDCAs) are thought to arise via beta
      oxidation of the corresponding dicarboxylic acids (DCAs), although long-chain
      DCAs are neither readily transported into nor beta-oxidized in mitochondria. We
      thus examined whether omega-hydroxylation of 3-hydroxy fatty acids (3-OHFAs),
      formed via incomplete mitochondrial oxidation, is a more likely pathway for 3
      OHDCA production. NADPH-fortified human liver microsomes converted 3
      hydroxystearate and 3-hydroxypalmitate to their omega-hydroxylated metabolites,
      3,18-dihydroxystearate and 3,16-dihydroxypalmitate, respectively, as identified
      by GC-MS. Rates of 3,18-dihydroxystearate and 3,16-dihydroxypalmitate formation
      were 1.23 +/- 0.5 and 1.46 +/- 0.30 nmol product formed/min/mg protein,
      respectively (mean +/- SD; n = 13). Polyspecific CYP4F antibodies markedly
      inhibited microsomal omega-hydroxylation of 3-hydroxystearate (68%) and 3
      hydroxypalmitate (99%), whereas CYP4A11 and CYP2E1 antibodies had little effect.
      Upon reconstitution, CYP4F11 and, to a lesser extent, CYP4F2 catalyzed omega
      hydroxylation of 3-hydroxystearate, whereas CYP4F3b, CYP4F12, and CYP4A11
      exhibited negligible activity. CYP4F11 was the lone CYP4F/A enzyme that
      effectively oxidized 3-hydroxypalmitate. Kinetic parameters of microsomal 3
      hydroxystearate metabolism were K(m) = 55 microM and V(max) = 8.33 min(-1),
      whereas those for 3-hydroxypalmitate were K(m) = 56.4 microM and V(max) = 14.2
      min(-1). CYP4F11 kinetic values resembled those of native microsomes, with K(m) =
      53.5 microM and V(max) = 13.9 min(-1) for 3-hydroxystearate and K(m) = 105.8
      microM and V(max) = 70.6 min(-1) for 3-hydroxypalmitate. Our data show that 3
      hydroxystearate and 3-hydroxypalmitate are converted to omega-hydroxylated 3
      OHDCA precursors in human liver and that CYP4F11 is the predominant catalyst of
      this reaction. CYP4F11-promoted omega-hydroxylation of 3-OHFAs may modulate the
      disposition of these compounds in pathological states in which enhanced fatty
      acid mobilization or impairment of mitochondrial fatty acid beta-oxidation
      increases circulating 3-OHFA levels.

PMID- 18065750
TI  - Right coronary artery flow impairment in patients with pulmonary hypertension.
AB  - AIMS: This study investigates whether increased right ventricular (RV) pressure
      in pulmonary hypertension (PH) impairs right coronary artery (RCA) flow and RV
      perfusion. METHODS: In 25 subjects, five patients with idiopathic pulmonary
      arterial hypertension, nine patients with chronic thromboembolic pulmonary
      arterial hypertension, and 11 healthy controls, flow of the RCA and left anterior
      descending (LAD) artery was measured with MR flow quantification. RESULTS: In PH,
      RCA peak systolic and mean systolic flow were lower, 1.02 +/- 0.62 mL/s and 0.42
      +/- 0.30 mL/s, than peak and mean diastolic flow, 2.99 +/- 1.97 mL/s (P < 0.001)
      and 1.73 +/- 0.97 mL/s (P < 0.001); a pattern similar to the LAD. In contrast, in
      controls, RCA peak and mean flow in systole, 1.63 +/- 0.58 mL/s and 0.72 +/- 0.23
      mL/s, were comparable to peak and mean flow in diastole, 1.72 +/- 0.48 mL/s and
      0.93 +/- 0.28 mL/s (NS). The systolic-to-diastolic flow ratio in the RCA, and
      mean flow per gram RV tissue, were inversely related to RV mass, R = -0.61 (P =
      0.009), and R = -0.73 (P < 0.001) and to RV pressure, R = -0.83 (P < 0.001), and
      R = -0.57 (P = 0.033). CONCLUSION: Although in controls, RCA flow is similar in
      systole and diastole, in PH there is systolic flow impediment, which is
      proportional to RV pressure and mass. In patients with severe RV hypertrophy
      total mean flow is reduced.

PMID- 18065751
TI  - Interpretation of the electrocardiogram: clinical correlation suggested.

PMID- 18065752
TI  - Transcatheter-covered stent implantation in an unusual post-surgical right
      ventricle outflow tract stenosis.

PMID- 18065753
TI  - An unappetizing dog bone: cardiac sarcoidosis presenting with heart block and
      unusual left ventricular bulging.

PMID- 18065754
TI  - Sinus node disease and arrhythmias in the long-term follow-up of former
      professional cyclists.
AB  - AIMS: Significant brady- and tachyarrhythmias may occur in active endurance
      athletes. It is controversial whether these arrhythmias do persist after
      cessation of competitive endurance training. METHODS AND RESULTS: Among all 134
      former Swiss professional cyclists [hereafter, former athletes (FAs)]
      participating at least once in the professional bicycle race Tour de Suisse in
      1955-1975, 62 (46%) were recruited for the study. The control group consisted of
      62 male golfers matched for age, weight, hypertension, and cardiac medication.
      All participants were screened with history, clinical and echocardiographic
      examination, ECG, and 24 h ECG. The time for the last bicycle race of FAs was 38
      +/- 6 years. The mean age at examination was 66 +/- 6 years in controls and 66 +/
      7 years in FAs (P = 0.47). The percentage of study participants with >4 h
      current cardiovascular training per week was identical. QRS duration (102 +/- 20
      vs. 95 +/- 13 ms, P = 0.03) and corrected QTc interval (416 +/- 27 vs. 404 +/-
      18, P = 0.004) were longer in FAs. There was no significant difference in the
      number of isolated atrial or ventricular premature complexes, or supraventricular
      tachycardias in the 24 h ECG; however, ventricular tachycardias tended to occur
      more often in FAs than in controls (15 vs. 3%, P = 0.05). The average heart rate
      was lower in FAs (66 +/- 9 vs. 70 +/- 8 b.p.m.) (P = 0.004). Paroxysmal or
      persistent atrial fibrillation or flutter was reported more often in FAs (P =
      0.028). Sinus node disease (SND), defined as bradycardia of <40 b.p.m. (10 vs.
      2%), atrial flutter (6 vs. 0%), pacemaker for bradyarrhythmias (3 vs. 0%), and/or
      maximal RR interval of >2.5 s (6 vs. 0%), was more common in FA (16%) than in
      controls (2%, P = 0.006). Observed survival of all FAs was not different from the
      expected. CONCLUSIONS: Among FAs, SND occurred significantly more often compared
      with age-matched controls, and there is trend towards more frequent ventricular
      tachycardias. Further studies have to evaluate prevention of arrhythmias with
      extreme endurance training, the necessity of regular follow-up of heart rhythm,
      and management of arrhythmias in former competitive endurance athletes.

PMID- 18065755
TI  - Marked defects in the expression and glycosylation of alpha2-HS
      glycoprotein/fetuin-A in plasma from neonates with intrauterine growth
      restriction: proteomics screening and potential clinical implications.
AB  - Intrauterine growth restriction (IUGR) has been associated with increased
      perinatal morbidity and mortality and increased morbidity and metabolic
      abnormalities later in life. IUGR is characterized as the failure of a fetus to
      achieve his or her genetic growth potential in utero. Altered protein expression
      profiles associated with IUGR may be informative on the pathologic mechanisms of
      this condition and might reveal potential markers for postnatal complications.
      The aim of this study was to compare protein profiles of umbilical cord plasma
      from IUGR and appropriate for gestational age full-term neonates. Blood samples
      from doubly clamped umbilical cord at delivery from 10 IUGR and 10 appropriate
      for gestational age full-term neonates were analyzed by two-dimensional
      electrophoresis and MS. Prominent changes of the alpha2-HS glycoprotein/fetuin-A
      were observed in IUGR cases. Specifically we showed that these changes occur
      primarily at the level of post-translational modifications of the protein. Using
      a combination of mass spectrometry and classical biochemical assays, single and
      heavy chain forms of fetuin-A were found to lack the normally present O-linked
      sialic acids in IUGR neonates. Fetuin A is a glycoprotein that has been
      associated with promotion of in vitro cell replication, fetal growth and
      osteogenesis, and protection from Gram-negative bacterial endotoxins. Prominent
      defects in glycosylation/sialylation of fetuin-A revealed by our study might be
      responsible for impaired function of fetuin-A, leading to deficient fetal growth,
      especially osteogenesis, and/or to the development of complications frequently
      seen later in the lives of IUGR neonates.

PMID- 18065756
TI  - The tale of two domains: proteomics and genomics analysis of SMYD2, a new histone
      methyltransferase.
AB  - Very little is known about SET- and MYND-containing protein 2 (SMYD2), a member
      of the SMYD protein family. However, the interest in better understanding the
      roles of SMYD2 has grown because of recent reports indicating that SMYD2
      methylates p53 and histone H3. In this study, we present a combined proteomics
      and genomics study of SMYD2 designed to elucidate its molecular roles. We report
      the cytosolic and nuclear interactome of SMYD2 using a combination of
      immunoprecipitation coupled with high throughput MS, chromatin
      immunoprecipitation coupled with high throughput MS, and co-immunoprecipitation
      methods. In particular, we report that SMYD2 interacted with HSP90alpha
      independently of the SET and MYND domains, with EBP41L3 through the MYND domain,
      and with p53 through the SET domain. We demonstrated that the interaction of
      SMYD2 with HSP90alpha enhances SMYD2 histone methyltransferase activity and
      specificity for histone H3 at lysine 4 (H3K4) in vitro. Interestingly histone
      H3K36 methyltransferase activity was independent of its interaction with
      HSP90alpha similar to LSD1 dependence on the androgen receptor. We also showed
      that the SET domain is required for the methylation at H3K4. We demonstrated
      using a modified chromatin immunoprecipitation protocol that the SMYD2 gain of
      function leads to an increase in H3K4 methylation in vivo, whereas no observable
      levels of H3K36 were detected. We also report that the SMYD2 gain of function was
      correlated with the up-regulation of 37 and down-regulation of four genes, the
      majority of which are involved in the cell cycle, chromatin remodeling, and
      transcriptional regulation. TACC2 is one of the genes up-regulated as a result of
      SMYD2 gain of function. Up-regulation of TACC2 by SMYD2 occurred as a result of
      SMYD2 binding to the TACC2 promoter where it methylates H3K4. Furthermore the
      combination of the SMYD2 interactome with the gene expression data suggests that
      some of the genes regulated by SMYD2 are closely associated with SMYD2
      interacting proteins.

PMID- 18065757
TI  - Using control charts to monitor quality of hospital care with administrative
      data.
AB  - OBJECTIVE: Nearly all hospital-specific comparative analyses, based on
      administrative data, are presented using cross-sectional displays. In this paper,
      we compare cross-sectional analyses with sequential monitoring using control
      charts. DESIGN:  ANALYSIS: of administrative data to compare cross-sectional
      funnel plots with one type of control chart: the risk-adjusted, expected-minus
      observed plot. SETTING: Eighteen tertiary and base hospitals in Queensland,
      Australia, for the two financial years 2003-04 and 2004-05. PARTICIPANTS:
      Patients admitted with acute myocardial infarction. MAIN OUTCOME MEASURE: Risk
      adjusted, 30-day, in-hospital, mortality rates. RESULTS: There were no outliers
      on the cross-sectional funnel plots for either of the 2 years using three-sigma
      limits and three low-outliers and one high-outlier using two-sigma limits. One
      reasonable interpretation of these plots is that most of the variations are due
      to statistical noise and there is little to be learnt by seeking to understand
      the reasons for variation across hospitals. In contrast, for the control charts,
      28% of hospitals signalled for a relative increase of 75% above that for all
      hospitals combined. CONCLUSION: If the aim of clinical indicators based on
      administrative data is to provide a starting point for learning, then control
      charting provides potentially more useful information than the more commonly used
      cross-sectional analyses. Control charts provide an understandable and up-to-date
      overview that allows early detection of runs of good or bad outcomes that can
      help hospitals identify areas for more in-depth self-monitoring and learning.

PMID- 18065758
TI  - Health staff perception regarding quality of delivered information to inpatients.
AB  - BACKGROUND: Accreditation usually requires that healthcare staff assess the
      quality of care delivered to patients in their own hospitals. It is unknown
      whether this assessment depends on the workplace rather than on the professional
      category of health personnel. OBJECTIVE: We aimed to identify major determinants
      of the perception of various categories of healthcare professionals concerning
      the quality of delivered information to inpatients in their ward, with a
      perspective to help the development of recommendations on how to compose self
      assessment teams for the accreditation process. METHOD: A self-administered
      questionnaire survey was conducted in nine wards from five short-stay hospitals
      in Paris, France. Three hundred and fifteen healthcare professionals (physicians,
      nurses and nursing assistants) were included. The views of various categories of
      healthcare professionals regarding the compliance with a set of quality standards
      were compared by nonparametric statistical analyses. Determinants of the self
      assessment of quality of care, including ward effect, were identified by fitting
      the data to a hierarchical model. RESULTS: The participation rate was 86%, with
      272 respondents (58 physicians, 149 nurses and 65 nursing assistants). Overall
      perceptions of various categories of healthcare professionals were not different.
      The final hierarchical model showed a strong ward effect (intracluster
      correlation coefficient=0.06, P<0.01) and a significant relationship between age
      of professionals and their opinion about quality of care. CONCLUSION: We observed
      a ward cluster effect on healthcare staff perception of quality, but the category
      of healthcare professional was not a determinant. A satisfactory
      representativeness on age of professionals selected into the teams in charge of
      self-assessment during hospital accreditation is recommended.

PMID- 18065759
TI  - Flagellin glycosylation in Pseudomonas aeruginosa PAK requires the O-antigen
      biosynthesis enzyme WbpO.
AB  - Pseudomonas aeruginosa PAK (serotype O6) produces a single polar, glycosylated
      flagellum composed of a-type flagellin. To determine whether or not flagellin
      glycosylation in this serotype requires O-antigen genes, flagellin was isolated
      from the wild type, three O-antigen-deficient mutants wbpL, wbpO, and wbpP, and a
      wbpO mutant complemented with a plasmid containing a wild-type copy of wbpO.
      Flagellin from the wbpO mutant was smaller (42 kDa) than that of the wild type
      (45 kDa), or other mutants strains, and exhibited an altered isoelectric point
      (pI 4.8) when compared with PAK flagellin (pI 4.6). These differences were
      because of the truncation of the glycan moiety in the wbpO-flagellin. Thus,
      flagellin glycosylation in P. aeruginosa PAK apparently requires a functional
      WbpO but not WbpP. Because WbpP was previously proposed to catalyze a metabolic
      step in the biosynthesis of B-band O-antigen that precedes the action of WbpO,
      these results prompted us to reevaluate the two-step pathway catalyzed by WbpO
      and WbpP. Results from WbpO-WbpP-coupled enzymatic assays showed that either WbpO
      or WbpP is capable of initiating the two-step pathway; however, the kinetic
      parameters favored the WbpO reaction to occur first, converting UDP-N-acetyl-D
      glucosamine to UDP-N-acetyl-D-glucuronic acid prior to the conversion to UDP-N
      acetyl-D-galacturonic acid by WbpP. This is the first report to show that a C4
      epimerase could utilize UDP-N-acetylhexuronic acid as a substrate.

PMID- 18065760
TI  - Interleukin-6 (IL-6) and/or soluble IL-6 receptor down-regulation of human type
      II collagen gene expression in articular chondrocytes requires a decrease of
      Sp1.Sp3 ratio and of the binding activity of both factors to the COL2A1 promoter.
AB  - Type II collagen is composed of alpha1(II) chains encoded by the COL2A1 gene.
      Alteration of this cartilage marker is a common feature of osteoarthritis.
      Interleukin-6 (IL-6) is a pro-inflammatory cytokine that needs a soluble form of
      receptor called sIL-6R to exert its effects in some cellular models. In that
      case, sIL-6R exerts agonistic action. This mechanism can make up for the partial
      or total absence of membrane-anchored IL-6 receptors in some cell types, such as
      chondrocytes. Our study shows that IL-6, sIL-6R, or both inhibit type II collagen
      production by rabbit articular chondrocytes through a transcriptional control.
      The cytokine and/or sIL-6R repress COL2A1 transcription by a -63/-35 sequence
      that binds Sp1.Sp3. Indeed, IL-6 and/or sIL-6R inhibit Sp1 and Sp3 expression and
      their binding activity to the 63-bp promoter. In chromatin immunoprecipitation
      experiments, IL-6.sIL-6R induced an increase in Sp3 recruitment to the detriment
      of Sp1. Knockdown of Sp1.Sp3 by small interference RNA and decoy strategies were
      found to prevent the IL-6- and/or sIL-6R-induced inhibition of COL2A1
      transcription, indicating that each of these Sp proteins is required for down
      regulation of the target gene and that a heterotypic Sp1.Sp3 complex is involved.
      Additionally, Sp1 was shown to interact with Sp3 and HDAC1. Indeed,
      overexpression of a full-length Sp3 cDNA blocked the Sp1 up-regulation of the 63
      bp COL2A1 promoter activity, and by itself, inhibits COL2A1 transcription. We can
      conclude that IL-6, sIL-6R, or both in combination decrease both the Sp1.Sp3
      ratio and DNA-binding activities, thus inhibiting COL2A1 transcription.

PMID- 18065761
TI  - Heparin-induced cis- and trans-dimerization modes of the thrombospondin-1 N
      terminal domain.
AB  - Through its interactions with proteins and proteoglycans, thrombospondin-1 (TSP
      1) functions at the interface of the cell membrane and the extracellular matrix
      to regulate matrix structure and cellular phenotype. We have previously
      determined the structure of the high affinity heparin-binding domain of TSP-1,
      designated TSPN-1, in association with the synthetic heparin, Arixtra. To
      establish that the binding of TSPN-1 to Arixtra is representative of the
      association with naturally occurring heparins, we have determined the structures
      of TSPN-1 in complex with heparin oligosaccharides containing eight (dp8) and ten
      (dp10) subunits, by x-ray crystallography. We have found that dp8 and dp10 bind
      to TSPN-1 in a manner similar to Arixtra and that dp8 and dp10 induce the
      formation of trans and cis TSPN-1 dimers, respectively. In silico docking
      calculations partnered with our crystal structures support the importance of
      arginine residues in positions 29, 42, and 77 in binding sulfate groups of the
      dp8 and dp10 forms of heparin. The ability of several TSPN-1 domains to bind to
      glycosaminoglycans simultaneously probably increases the affinity of binding
      through multivalent interactions. The formation of cis and trans dimers of the
      TSPN-1 domain with relatively short segments of heparin further enhances the
      ability of TSP-1 to participate in high affinity binding to glycosaminoglycans.
      Dimer formation may also involve TSPN-1 domains from two separate TSP-1
      molecules. This association would enable glycosaminoglycans to cluster TSP-1.

PMID- 18065762
TI  - Identification of disulfide-linked dimers of the receptor tyrosine kinase DDR1.
AB  - Discoidin domain receptor 1 (DDR1) is a transmembrane receptor tyrosine kinase
      activated by triple-helical collagen. So far six different isoforms of DDR1 have
      been described. Aberrant expression and signaling of DDR1 have been implicated in
      several human diseases linked to accelerated matrix degradation and remodeling,
      including tumor invasion, atherosclerosis, and lung fibrosis. Here we show that
      DDR1 exists as a disulfide-linked dimer in transfected as well as endogenously
      expressing cells. This dimer formation occurred irrespective of its kinase
      domain, as dimers were also found for the truncated DDR1d isoform. A deletion
      analysis of the extracellular domain showed that DDR1 mutants lacking the stalk
      region failed to form dimers, whereas deletion of the discoidin domain did not
      prevent dimerization. Point mutagenesis within the stalk region suggested that
      cysteines 303 and 348 are necessary for dimerization, collagen binding, and
      activation of kinase function. The identification of DDR1 dimers provides new
      insights into the molecular structure of receptor tyrosine kinases and suggests
      distinct signaling mechanisms of each receptor subfamily.

PMID- 18065763
TI  - Proteomic analysis of the cyanobacterium of the Azolla symbiosis: identity,
      adaptation, and NifH modification.
AB  - Cyanobacteria are able to form stable nitrogen-fixing symbioses with diverse
      eukaryotes. To extend our understanding of adaptations imposed by plant hosts,
      two-dimensional gel electrophoresis and mass spectrometry (MS) were used for
      comparative protein expression profiling of a cyanobacterium (cyanobiont)
      dwelling in leaf cavities of the water-fern Azolla filiculoides. Homology-based
      protein identification using peptide mass fingerprinting [matrix-assisted laser
      desorption ionization-time of flight (MALDI-TOF-MS)], tandem MS analyses, and
      sequence homology searches resulted in an identification success rate of 79% of
      proteins analysed in the unsequenced cyanobiont. Compared with a free-living
      strain, processes related to energy production, nitrogen and carbon metabolism,
      and stress-related functions were up-regulated in the cyanobiont while
      photosynthesis and metabolic turnover rates were down-regulated, stressing a slow
      heterotrophic mode of growth, as well as high heterocyst frequencies and nitrogen
      fixing capacities. The first molecular data set on the nature of the NifH post
      translational modification in cyanobacteria was also obtained: peptide mass
      spectra of the protein demonstrated the presence of a 300-400 Da protein
      modification localized to a specific 13 amino acid sequence, within the part of
      the protein that is ADP-ribosylated in other bacteria and close to the active
      site of nitrogenase. Furthermore, the distribution of the highest scoring
      database hits for the identified proteins points to the possibility of using
      proteomic data in taxonomy.

PMID- 18065764
TI  - Loss of viability of tomato pollen during long-term dry storage is associated
      with reduced capacity for translating polyamine biosynthetic enzyme genes after
      rehydration.
AB  - The possibility that a loss of pollen viability during dry storage in a freezer
      is caused by the reduced pollen capacity to enhance polyamine biosynthetic enzyme
      activity after rehydration was investigated using pollen grains of tomato
      (Solanum lycopersicum=Lycopersicon esculentum) stored at -30 degrees C under dry
      conditions for up to 42 months. Pollen grains showed normal germinability for at
      least 12 months in storage, but those stored for longer than 24 months exhibited
      a significant reduction in germinability and fruit-setting ability. This age
      dependent reduction in pollen viability coincided with the extent to which the
      pollen lost the capacity to increase arginine decarboxylase (ADC) and S
      adenosylmethionine decarboxylase (SAMDC) activities and polyamine contents upon
      rehydration. Immunoblot analysis indicated that the capacity of pollen to
      translate ADC and SAMDC mRNAs was impaired in accordance with the loss of
      viability. Also, the capacity to synthesize proteins in general decreased with
      the increase in storage duration. The addition of 1 mM putrescine, spermidine, or
      spermine to incubation medium promoted germination, impregnation of pollen grains
      with 1 mM spermidine restored fertilization ability, and the addition of 1 mM
      spermidine to incubation medium promoted protein synthesis exclusively in pollen
      grains which had been stored for a long time. These results indicate that the
      reduction in viability of tomato pollen during long-term dry storage in a freezer
      involves a decline in the capacity to enhance gene translation for polyamine
      biosynthetic enzymes upon rehydration.

PMID- 18065765
TI  - Tissue specialization at the metabolite level is perceived during the development
      of tomato fruit.
AB  - Fruit maturation and tissue differentiation are important topics in plant
      physiology. These biological phenomena are accompanied by specific alterations in
      the biological system, such as differences in the type and concentration of
      metabolites. The secondary metabolism of tomato (Solanum lycopersicum) fruit was
      monitored by using liquid chromatography (LC) coupled to photo-diode array (PDA)
      detection, fluorescence detection (FD), and mass spectrometry (MS). Through this
      integrated approach different classes of compounds were analysed: carotenoids,
      xanthophylls, chlorophylls, tocopherols, ascorbic acid, flavonoids, phenolic
      acids, glycoalkaloids, saponins, and other glycosylated derivatives. Related
      metabolite profiles of peel and flesh were found between several commercial
      tomato cultivars indicating similar metabolite trends despite the genetic
      background. For a single tomato cultivar, metabolite profiles of different fruit
      tissues (vascular attachment region, columella and placenta, epidermis, pericarp,
      and jelly parenchyma) were examined at the green, breaker, turning, pink, and red
      stages of fruit development. Unrelated to the chemical nature of the metabolites,
      behavioural patterns could be assigned to specific ripening stages or tissues.
      These findings suggest spatio-temporal specificity in the accumulation of
      endogenous metabolites from tomato fruit.

PMID- 18065766
TI  - Light and turgor affect the water permeability (aquaporins) of parenchyma cells
      in the midrib of leaves of Zea mays.
AB  - In response to light, water relation parameters (turgor, half-time of water
      exchange, T(1/2), and hydraulic conductivity, Lp; T(1/2) proportional 1/Lp) of
      individual cells of parenchyma sitting in the midrib of leaves of intact corn
      (Zea mays L.) plants were investigated using a cell pressure probe. Parenchyma
      cells were used as model cells for the leaf mesophyll, because they are close to
      photosynthetically active cells at the abaxial surface, and there are stomata at
      both the adaxial and abaxial sides. Turgor ranged from 0.2 to 1.0 MPa under
      laboratory light condition (40 micromol m(-2) s(-1) at the tissue level), and
      individual cells could be measured for up to 6 h avoiding the variability between
      cells. In accordance with earlier findings, there was a big variability in
      T(1/2)s measured ranging from 0.5 s to 100 s, but the action of light on T(1/2)s
      could nevertheless be worked out for cells having T(1/2)s greater than 2 s.
      Increasing light intensity ranging from 100 micromol m(-2) s(-1) to 650 micromol
      m(-2) s(-1) decreased T(1/2) by a factor up to five within 10 min and increased
      Lp (and aquaporin activity) by the same factor. In the presence of light, turgor
      decreased due to an increase in transpiration, and this tended to compensate or
      even overcompensated for the effect of light on T(1/2). For example, during
      prolonged illumination, cell turgor dropped from 0.2 to 1.0 MPa to -0.03 to 0.4
      MPa, and this drop caused an increase of T(1/2) and a reduction of cell Lp, i.e.
      there was an effect of turgor on cell Lp besides that of light. To separate the
      two effects, cell turgor (water potential) was kept constant while changing light
      intensity by applying gas pressure to the roots using a pressure chamber. At a
      light intensity of 160 micromol m(-2) s(-1), there was a reduction of T(1/2) by a
      factor of 2.5 after 10-30 min, when turgor was constant within +/-0.05 MPa.
      Overall, the effects of light on T(1/2) (Lp) were overriding those of turgor only
      when decreases in turgor were less than about 0.2 MPa. Otherwise, turgor became
      the dominant factor. The results indicate that the hydraulic conductivity
      increased with increasing light intensity tending to improve the water status of
      the shoot. However, when transpiration induced by light tends to cause a low
      turgidity of the tissue, cell Lp was reduced. It is concluded that, when
      measuring the overall hydraulic conductivity of leaves, both the effects of light
      and turgor should be considered. Although the mechanism(s) of how light and
      turgor influence the cell Lp is still missing, it most likely involves the gating
      of aquaporins by both parameters.

PMID- 18065767
TI  - Jasmonates and its mimics differentially elicit systemic defence responses in
      Nicotiana attenuata.
AB  - Coronalon (6-ethyl indanoyl isoleucine), a synthetic jasmonate mimic, is known to
      regulate levels of transcripts and secondary metabolites that are commonly
      elicited by methyl jasmonate (MeJA) in a variety of plants. The ability of
      coronalon and its derivative (In-L-Ile-Me) to elicit MeJA-activated
      transcriptional and defence responses [nicotine and trypsin proteinase inhibitors
      (TPIs)] was compared in treated and systemic untreated tissues of wild-type (WT)
      and NaLOX3-silenced Nicotiana attenuata plants which are unable to activate
      either local or systemic defence responses. Coronalon and its derivative
      significantly regulated 71% and 86% of genes up-regulated by MeJA and 53% and 66%
      of the genes down-regulated by MeJA in the treated leaves, but only 3% and 7% of
      all regulated genes in untreated, but phylotactically connected, leaves of WT
      plants. Consistent with their ability to elicit transcriptional responses in
      treated tissues, coronalon and In-L-Ile-Me increased nicotine and TPIs when
      applied to the tissues in which these metabolites are produced, namely roots and
      leaves. However, treating roots elicited TPI activity in leaves in both WT and
      NaLOX3-silenced plants, suggesting that mimics can be transported apoplastically
      from roots to leaves in the xylem. This response was lower in NaLOX3-silenced
      plants, suggesting that the ability of coronalon and In-L-Ile-Me to elicit TPI
      responses in leaves after root treatments requires intact jasmonic acid (JA)
      signalling. Treating leaves did not elicit detectable changes in endogenous JA
      levels but did decrease free salicylic acid contents. It is concluded that
      coronalon and In-L-Ile-Me elicit jasmonate responses in treated tissues and could
      be valuable tools for dissecting local and systemic jasmonate signalling networks
      in plants.

PMID- 18065768
TI  - Aryl hydrocarbon receptor mediates laminar fluid shear stress-induced CYP1A1
      activation and cell cycle arrest in vascular endothelial cells.
AB  - AIMS: We investigated the mechanisms of shear stress (SS)-induced activation of
      cytochrome P450 (CYP) 1A1 and cell cycle arrest with regard to the role of the
      aryl hydrocarbon receptor (AhR), since AhR mediates the expression of CYP1A1
      induced by polycyclic aromatic hydrocarbons (PAHs) and is thought to be involved
      in the regulation of cell growth and differentiation. METHODS AND RESULTS: Human
      umbilical vein endothelial cells (ECs) were exposed to laminar SS and thereafter
      collected to evaluate the expression, activity, and transcription of CYP1A1 and
      the expression of AhR and cell cycle-related proteins. A physiological level of
      laminar SS (15 dynes/cm(2)) markedly increased the expression level and enzymatic
      activity of CYP1A1. SS stimulated CYP1A1 promoter activity without influencing
      mRNA stability. Loss of two functional xenobiotic response elements (XREs) in the
      5'-flanking region of the CYP1A1 gene suppressed the SS-induced transcription of
      CYP1A1. Laminar SS stimulated the expression and nuclear translocation of AhR.
      alpha-Naphthoflavone, an AhR antagonist, and a small interfering RNA (siRNA) for
      AhR significantly suppressed SS-induced CYP1A1 expression. The siRNA also
      abolished SS-induced cell cycle arrest, the expression of the cyclin-dependent
      kinase inhibitor p21(Cip1), and dephosphorylation of retinoblastoma protein.
      CONCLUSION: Laminar SS stimulated the transcription of CYP1A1 through the
      activation of AhR in a way that is similar to the effects of PAHs. AhR was also
      involved in cell cycle arrest induced by SS. Our results suggest that sustained
      activation of AhR exposed to blood flow plays an important role in the regulation
      of EC functions.

PMID- 18065769
TI  - Caveolin-1 interacts and cooperates with the transforming growth factor-beta type
      I receptor ALK1 in endothelial caveolae.
AB  - AIMS: Activin receptor-like kinase (ALK)1 is a transforming growth factor (TGF)
      beta type I membrane receptor restricted almost entirely to endothelial cells
      (ECs) and involved in vascular remodelling and angiogenesis. Previous reports
      have shown that the ubiquitous TGF-beta type I receptor ALK5 and the type II
      receptor are located in cholesterol-rich membrane microdomains named caveolae.
      The aim of this work was to assess the location of ALK1 in endothelial caveolae
      as well as to study the role of caveolin-1 on the TGF-beta/ALK1 signalling
      pathway. METHODS AND RESULTS: The subcellular distribution of ALK1 was analysed
      by confocal microscopy and co-fractionation experiments in human ECs. The
      association between human ALK1 and caveolin-1 was studied in caveolin-1-deficient
      human epithelial cells by co-immunoprecipitation. The functional role of caveolin
      1 on the ALK1-mediated TGF-beta signalling was elucidated using ALK1-specific
      luciferase reporters in human ECs, caveolin-1(-/-)mouse embryonic fibroblasts,
      and rat myoblasts. Confocal microscopy analyses, as well as cholesterol depletion
      experiments in the presence of cholesterol-depleting agents such as nystatin or
      methyl-beta-cyclodextrin, demonstrated that ALK1 is located in endothelial
      caveolae. Also, co-immunoprecipitation assays showed that ALK1 associates with
      the main caveolae component caveolin-1. Mapping of the ALK1/caveolin-1
      interaction revealed that the caveolin-1 scaffolding domain and the caveolin-1
      binding motif in ALK1 are responsible for this association. Moreover, this
      hitherto not reported interaction had a functional consequence for the ALK1
      dependent signalling. In contrast with the previously published ALK5/caveolin-1
      interaction, caveolin-1 enhances the TGF-beta/ALK1 signalling pathway, promoting
      the activity of the ALK1-specific reporters. Conversely, specific suppression of
      caveolin-1 abrogated the ALK1 signalling pathway. CONCLUSION: ALK1 is located in
      endothelial caveolae where it functionally interacts with caveolin-1 through its
      scaffolding domain, suggesting a joint contribution of ALK1 and caveolin-1 as key
      mediators of the TGF-beta pathway in angiogenesis.

PMID- 18065770
TI  - VEGF-C induced angiogenesis preferentially occurs at a distance from
      lymphangiogenesis.
AB  - AIMS: Vascular endothelial growth factor-C (VEGF-C) has been shown to stimulate
      both angiogenesis and lymphangiogenesis in some but not all models where VEGF-C
      is over-expressed. Our aim was to investigate the interaction between
      lymphangiogenesis and angiogenesis in adult tissues regulated by VEGF-C and
      identify evidence of polarized growth of lymphatics driven by specialized cells
      at the tip of the growing sprout. METHODS AND RESULTS: We used an adult model of
      lymphangiogenesis in the rat mesentery. The angiogenic effect of VEGF-C was
      markedly attenuated in the presence of a growing lymphatic network. Furthermore,
      we show that this growth of lymphatic vessels can occur both by recruitment of
      isolated lymphatic islands to a connected network and by filopodial sprouting.
      The latter is independent of polarized tip cell differentiation that can be
      generated all along lymphatic capillaries, independently of the proliferation
      status of the lymphatic endothelial cells. CONCLUSION: These results both
      demonstrate a dependence of VEGF-C-mediated angiogenesis on lymphatic vascular
      networks and indicate that the mechanism of VEGF-C-mediated lymphangiogenesis is
      different from that of classical angiogenic mechanisms.

PMID- 18065772
TI  - Computational toxicology--a state of the science mini review.
AB  - Advances in computer sciences and hardware combined with equally significant
      developments in molecular biology and chemistry are providing toxicology with a
      powerful new tool box. This tool box of computational models promises to increase
      the efficiency and the effectiveness by which the hazards and risks of
      environmental chemicals are determined. Computational toxicology focuses on
      applying these tools across many scales, including vastly increasing the numbers
      of chemicals and the types of biological interactions that can be evaluated. In
      addition, knowledge of toxicity pathways gathered within the tool box will be
      directly applicable to the study of the biological responses across a range of
      dose levels, including those more likely to be representative of exposures to the
      human population. Progress in this field will facilitate the transformative shift
      called for in the recent report on toxicology in the 21st century by the National
      Research Council. This review surveys the state of the art in many areas of
      computational toxicology and points to several hurdles that will be important to
      overcome as the field moves forward. Proof-of-concept studies need to clearly
      demonstrate the additional predictive power gained from these tools. More
      researchers need to become comfortable working with both the data generating
      tools and the computational modeling capabilities, and regulatory authorities
      must show a willingness to the embrace new approaches as they gain scientific
      acceptance. The next few years should witness the early fruits of these efforts,
      but as the National Research Council indicates, the paradigm shift will take a
      long term investment and commitment to reach full potential.

PMID- 18065771
TI  - Modulation of the myocardial redox state by vagal nerve stimulation after
      experimental myocardial infarction.
AB  - AIMS: Redox alteration plays a major role in the pathogenesis of heart failure
      (HF). Since vagal nerve stimulation (VNS) is known to improve survival and
      attenuate cardiac remodelling, we hypothesized that VNS may modulate the
      myocardial redox state. METHODS AND RESULTS: Using a chronic HF mouse model, we
      applied VNS for 15 min and measured myocardial redox status using in vivo
      electron spin resonance spectroscopy. Signal decay rate of the nitroxyl probe, an
      index of redox status, was enhanced in HF compared with sham (0.16 +/- 0.01 vs.
      0.13 +/- 0.01 min(-1), P < 0.05; n = 6), and VNS normalized this enhancement
      (0.13 +/- 0.01 min(-1), P < 0.05). Atropine sulphate abolished the VNS effects,
      indicating that the VNS modulates myocardial redox state via muscarinic
      receptors. N(omega)-Nitro-L-arginine methyl ester treatment and fixed-rate atrial
      pacing showed a trend to suppress the VNS effects, suggesting the involvement of
      nitric oxide-based signalling and myocardial oxygen consumption. Moreover, VNS
      decreased the myocardial norepinephrine (NE) level (0.25 +/- 0.07 vs. 0.60 +/-
      0.12 ng/mL, P < 0.05; n = 6). Reactive oxygen species production from cultured
      cardiomyocytes was enhanced by beta-adrenergic activation, which was partially
      antagonized by 10 micromol/L acetylcholine (ACh) (relative value compared with
      control: NE 3.7 +/- 0.5, NE + ACh 2.5 +/- 0.3, P < 0.05; n = 12). CONCLUSION: The
      present study suggests that VNS modulates the cardiac redox status and adrenergic
      drive, and thereby suppresses free radical generation in the failing heart.

PMID- 18065773
TI  - 4-tert-octylphenol regulates the differentiation of C3H10T1/2 cells into
      osteoblast and adipocyte lineages.
AB  - The aim of this study was to investigate whether 4-tert-octylphenol (OP) affects
      the differentiation of multipotent C3H10T1/2 cells, a cell line established from
      mouse embryonic connective tissue, into osteoblast and adipocyte lineages.
      Confluent C3H10T1/2 cells were incubated for 7 days with (OP-treated cultures) or
      without (control cultures) 15 microg/ml of OP. The 7-day treatment of confluent
      cells with OP decreased alkaline phosphatase activity by 81%, inhibited the
      expression of transforming growth factor beta2, and inhibited the morphological
      changes in cells to an osteoblastic appearance. These results indicate that the 7
      day treatment of confluent C3H10T1/2 cells with OP inhibited their
      differentiation into osteoblasts. Since this treatment strongly induced the
      expression of peroxisome proliferator-activated receptor r (PPARr) but did not
      stimulate triacylglycerol (TG) accumulation in cells, C3H10T1/2 cells in the
      control and OP-treated cultures were incubated for 2 days with a hormone mixture
      (insulin [INS], dexamethasone, and 1-methyl-3-isobutylxanthine) and incubated for
      an additional 5 days with INS alone. The TG and adiponectin contents of the OP
      treated cultures were 4.2 and 4.1 times higher, respectively, than those of the
      control cultures. There were many more Oil Red O-staining cells in the OP-treated
      cultures than in the control cultures. The expression of PPARr in the OP-treated
      cultures was higher than that in the control cultures. These results indicate
      that the OP-treated cultures contained a larger number of adipocytes than the
      control cultures. In conclusion, treatment of C3H10T1/2 cells with OP inhibited
      osteoblast differentiation, causing a lineage shift toward adipocytes.

PMID- 18065774
TI  - Changes in reproductive courtship behaviors of adult American kestrels (Falco
      sparverius) exposed to environmentally relevant levels of the polybrominated
      diphenyl ether mixture, DE-71.
AB  - Polybrominated diphenyl ethers (PBDEs) are increasing in biota. Here, captive
      adult American kestrels were exposed daily by diet to safflower oil (controls),
      or one of two levels of a pentaBDE technical formulation, DE-71 (0.3 or 1.6 ppm),
      for approximately 75 days, commencing 21 days before breeding. This exposure
      resulted in eggs having PBDE concentrations similar (low exposure) or within the
      same order of magnitude (high exposure) reported for wild American kestrels and
      gulls in the Great Lakes. Compared to controls, kestrels in both exposure groups
      copulated less, spent less time in their nest boxes, and participated in fewer
      pair-bonding behaviors. Furthermore, the timing of these behaviors, which is
      important to creating and maintaining the pair-bond, also differed significantly
      from the controls. The females in the low-exposure group made fewer compatible
      trilling calls and ate less frequently. These behavioral changes were compounded
      by increasing exposure to DE-71 during the 9-day courtship period immediately
      preceding egg laying, a standard measure of the kestrel courtship period. The
      birds in the high-exposure group made more food transfers, excited "klee" calls,
      and copulations, the latter only when compared to the low-exposure birds, whereas
      the low-exposure males performed fewer pair-bonding behaviors. This study
      demonstrates that the exposure of kestrels to environmentally relevant levels of
      DE-71 modifies the quality of the pair-bond, affects the reproductive behavior of
      both sexes, and occurs when birds are exposed for a short period as adults. In
      addition, these behavioral effects are consistent with the observed reproductive
      changes in these birds.

PMID- 18065775
TI  - Modeling and assaying dioxin-like biological effects for both dioxin-like and
      certain non-dioxin-like compounds.
AB  - 13C NMR data have been correlated to Toxic Equivalency Factors (TEFs) of the 29
      PCDDs, PCDFs, or PCBs for which non-zero TEFs have been defined. Such
      correlations are called quantitative spectrometric data-activity relationship
      (QSDAR) models. An improved QSDAR model predicted TEFs of 0.037 and 0.004,
      respectively, for 1,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,4,7
      pentachlorodibenzo-p-dioxin (PeCDD), both among the 390 congeners for which zero
      value TEFs are assumed. A QSDAR model of Relative Potency (REP) values estimated
      the corresponding values as 0.115 and 0.020. Results from both models indicated
      that these two congeners may exhibit significant dioxin-like toxicity. If other
      such congeners have non-zero toxicity, TEF-based risk assessments of some dioxin
      , furan-, or PCB-contaminated sites or foods may underestimate toxicity. Both
      models were extensively cross-validated and the TEF model was externally
      validated. We confirmed the predictions by an independent in vitro method, a
      luciferase gene expression assay based on mouse liver cells that found REPs of
      0.027 and 0.013, respectively, for 1,3,7,8-TCDD and 1,2,3,4,7-PeCDD. The QSDAR
      estimated and gene-expression assayed values agreed. The models were used to
      predict activity for an applicability domain including 108 non-2,3,7,8 dioxin,
      furan, or PCB congeners and 2,3,7,8-tetrachlorophenothiazine, a dioxin analog
      proposed as a drug candidate. This study showed that QSDAR prediction followed by
      a relatively inexpensive in vitro assay could be used to nominate a few
      candidates among hundreds for further investigation. It suggested that in silico
      and in vitro nomination protocols may facilitate practical risk assessment when
      chemical family members exhibit different degrees of toxicity operating via a
      common mechanism.

PMID- 18065776
TI  - Ovule morphogenesis in Ranunculaceae and its systematic significance.
AB  - BACKGROUND AND AIMS: Ranunculaceae has a prominent phylogenetic position in
      Ranunculales which appears at the base of eudicots. The aims of the present paper
      are to reveal the features of ovule morphogenesis in different taxa and gain a
      better understanding of the systematics of Ranunculaceae. METHODS: Flowers of 17
      species from three subfamilies, nine tribes and 16 genera of Ranunculaceae, at
      successive developmental stages, were collected in the wild and studied with a
      scanning electron microscope. KEY RESULTS: The integuments in the unitegmic
      ovules in Helleborus, Ranunculus and Oxygraphis, as well as the inner integuments
      in the bitegmic genera, initiate annularly and eventually become cup-shaped.
      However, the integuments in the unitegmic ovules in Anemone and Clematis, as well
      as the outer integuments in the bitegmic genera, arise semi-annularly and
      eventually become hood-shaped. Different kinds of appendages appear on the ovules
      during development. In Coptis of subfamily Coptidoideae, a wrap-shaped appendage
      arises outside the ovule and envelopes the ovule entirely. In the genera of
      subfamily Thalictroideae and tribe Anemoneae of subfamily Ranunculoideae,
      appendages appear on the placenta, the funicle or both. In tribe Helleboreae of
      subfamily Ranunculoideae, an alary appendage is initiated where the integument
      and the funicle join and becomes hood-shaped. CONCLUSIONS: Ovule morphogenesis
      characteristics are significant in classification at the levels of subfamilies
      and tribes. The initiation patterns of the integuments and the development of
      appendages show diversity in Ranunculaceae. The present observations suggest that
      the bitegmic, hood-shaped outer integument and endostomic micropyle are primitive
      while the unitegmic, cupular-shaped outer integument and bistomic micropyle are
      derivative.

PMID- 18065777
TI  - Vision loss due to coincident ocular and central causes in a patient with
      Heidenhain variant Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD) is a degenerative disease of the brain associated
      with a rapidly progressive spongiform encephalopathy. Visual symptoms and neuro
      ophthalmological signs are not infrequent, and presentation to an ophthalmologist
      may result. A case is reported of an 89-years-old gentleman who presented with a
      short history of isolated deterioration in vision. He underwent ocular
      intervention but subsequently developed progressive dementia, asterixis,
      myoclonus, cerebellar and extrapyramidal signs, and cortical blindness. An
      electroencephalogram was consistent with CJD. The patient progressively
      deteriorated and died 9 weeks after symptom onset. Limited post-mortem
      examination confirmed CJD.

PMID- 18065778
TI  - AKT-sensitive or insensitive pathways of toxicity in glial cells and neurons in
      Drosophila models of Huntington's disease.
AB  - Huntington's disease (HD) is caused by an extended polyglutamine (polyQ) tract in
      the Huntingtin protein. Neuronal and glial dysfunction precedes the
      neurodegeneration and appears to be the primary cause for the early symptoms in
      HD. In recent years, development of Drosophila models of polyQ-related diseases
      facilitated research of candidate rescuer genes. In most cases, analysis in
      Drosophila was performed by assessing toxicity on retinal and/or brain neurons.
      However, none of the potential rescuers were evaluated on glial alterations. Here
      we used a genetic approach in Drosophila to characterize the phenotypic effects
      of mutant Huntingtin (mHtt) expressed in neurons or different glia subsets and we
      established a sensitive assay for evaluating modifiers of glial alterations. We
      determined the level of cell protection ensured by activation of the AKT and ERK
      anti-apoptotic kinases in the retina as well as in neurons and glia of the fly
      brain, compared with the rescuing effects of the HSP70 chaperone. We found that
      both AKT and HSP70 alleviated mHtt-induced toxicity in the retina. In contrast,
      their protective effects differed in the brain. HSP70 rescued neurodegeneration,
      locomotor defects and early lethality of flies expressing mHtt in neurons or
      glia. AKT failed to prevent brain neuronal death and lethality of flies, but
      significantly improved their locomotor performance when co-expressed with mHtt in
      glia. ERK had no beneficial effects in the retina or brain. These results
      indicate that mHtt activates distinct pathways of toxicity in Drosophila, either
      sensitive to AKT in retinal photoreceptors and glia, or independent in brain
      neurons.

PMID- 18065779
TI  - A scan for genetic determinants of human hair morphology: EDAR is associated with
      Asian hair thickness.
AB  - Hair morphology is one of the most differentiated traits among human populations.
      However, genetic backgrounds of hair morphological differences among populations
      have not been clarified yet. In addition, little is known about the evolutionary
      forces that have acted on hair morphology. To identify hair morphology
      determining genes, the levels of local genetic differentiation in 170 genes that
      are related to hair morphogenesis were evaluated by using data from the
      International HapMap project. Among highly differentiated genes, ectodysplasin A
      receptor (EDAR) harboring an Asian-specific non-synonymous single nucleotide
      polymorphism (1540T/C, 370Val/Ala) was identified as a strong candidate.
      Association studies between genotypes and hair morphology revealed that the Asian
      specific 1540C allele is associated with increase in hair thickness. Reporter
      gene assays suggested that 1540T/C affects the activity of the downstream
      transcription factor NF-kappaB. It was inferred from geographic distribution of
      1540T/C and the long-range haplotype test that 1540C arose after the divergence
      of Asians from Europeans and its frequency has rapidly increased in East Asian
      populations. These findings lead us to conclude that EDAR is a major genetic
      determinant of Asian hair thickness and the 1540C allele spread through Asian
      populations due to recent positive selection.

PMID- 18065780
TI  - Selective vulnerability of motor neurons and dissociation of pre- and post
      synaptic pathology at the neuromuscular junction in mouse models of spinal
      muscular atrophy.
AB  - Proximal spinal muscular atrophy (SMA) is a common autosomal recessive childhood
      form of motor neuron disease. Previous studies have highlighted nerve- and muscle
      specific events in SMA, including atrophy of muscle fibres and post-synaptic
      motor endplates, loss of lower motor neuron cell bodies and denervation of
      neuromuscular junctions caused by loss of pre-synaptic inputs. Here we have
      undertaken a detailed morphological investigation of neuromuscular synaptic
      pathology in the Smn-/-;SMN2 and Smn-/-;SMN2;Delta7 mouse models of SMA. We show
      that neuromuscular junctions in the transversus abdominis (TVA), levator auris
      longus (LAL) and lumbrical muscles were disrupted in both mouse models. Pre
      synaptic inputs were lost and abnormal accumulations of neurofilament were
      present, even in early/mid-symptomatic animals in the most severely affected
      muscle groups. Neuromuscular pathology was more extensive in the postural TVA
      muscle compared with the fast-twitch LAL and lumbrical muscles. Pre-synaptic
      pathology in Smn-/-;SMN2;Delta7 mice was reduced compared with Smn-/-;SMN2 mice
      at late-symptomatic time-points, although post-synaptic pathology was equally
      severe. We demonstrate that shrinkage of motor endplates does not correlate with
      loss of motor nerve terminals, signifying that one can occur in the absence of
      the other. We also demonstrate selective vulnerability of a subpopulation of
      motor neurons in the caudal muscle band of the LAL. Paralysis with botulinum
      toxin resulted in less terminal sprouting and ectopic synapse formation in the
      caudal band compared with the rostral band, suggesting that motor units
      conforming to a Fast Synapsing (FaSyn) phenotype are likely to be more vulnerable
      than those with a Delayed Synapsing (DeSyn) phenotype.

PMID- 18065781
TI  - Sex-dependent association of a common low-density lipoprotein receptor
      polymorphism with RNA splicing efficiency in the brain and Alzheimer's disease.
AB  - Since apoE allele status is the predominant Alzheimer's disease (AD) genetic risk
      factor, functional single nucleotide polymorphisms (SNPs) in brain apoE receptors
      represent excellent candidates for association with AD. Recently, we identified a
      SNP, rs688, as modulating the splicing efficiency of low-density lipoprotein
      receptor (LDLR) exon 12 in female human liver and in minigene-transfected HepG2
      cells. Moreover, the rs688T minor allele was associated with significantly higher
      LDL and total cholesterol in women within the Framingham Offspring Study cohort.
      Since LDLR is a major apoE receptor in the brain, we hypothesized that rs688
      modulates LDLR splicing in neural tissues and associates with AD. To evaluate
      this hypothesis, we first transfected LDLR minigenes into SH-SY5Y neuroblastoma
      cells and found that the rs688T allele reduces exon 12 inclusion in this neural
      model. We then evaluated the association of rs688 allele with exon 12 splicing
      efficiency in vivo by quantifying LDLR splicing in human anterior cingulate
      tissue obtained at autopsy; the rs688T allele is associated with decreased LDLR
      exon 12 splicing efficiency in aged males, but not females. Lastly, we evaluated
      whether rs688 associates with AD by genotyping DNA from 1457 men and 2055 women
      drawn from three case-control series. The rs688T/T genotype was associated with
      increased AD odds in males [recessive model, odds ratio (OR) of 1.49, 95%
      confidence interval (CI) of 1.13-1.97, uncorrected P = 0.005], but not in
      females. In summary, these studies identify a functional apoE receptor SNP that
      is associated with AD in a sex-dependent fashion.

PMID- 18065782
TI  - Renal and cardiac effects of antihypertensive treatment with ramipril versus
      metoprolol in autosomal dominant polycystic kidney disease.

PMID- 18065783
TI  - Proteinuria in children with sickle cell disease.
AB  - BACKGROUND: Sickle cell nephropathy is characterized by proteinuria that starts
      in childhood and may lead to renal failure. Microalbuminuria is used as a marker
      of glomerular damage. There are no data on the extent and type of proteinuria
      other than microalbuminuria in children with sickle cell disease (SCD). Our goal
      was characterization of glomerular permselectivity and tubular proteinuria in
      children with SCD. The improved characterization will allow earlier recognition
      and prevention of renal damage. METHODS: Thirty-two stable patients with
      haemoglobin SS (HbSS) (15 boys and 17 girls, age 9.57 +/- 5.45 years, 8 months to
      19 years) were investigated. All patients had normal renal function and tested
      negative for proteinuria with a dipstick method. Markers of glomerular
      permselectivity used were albumin (marker of charge selectivity and less severe
      pore-size selectivity) and immunoglobulin G (IgG, marker of more severe pore-size
      selectivity). The marker of tubular injury used was retinol-binding protein (RBP,
      marker of proximal tubular dysfunction). These proteins were measured in urine
      spot samples using nephelometry. We did not include a control group as values in
      healthy subjects were previously published. RESULTS: Total protein excretion was
      elevated in 41% (13/32) of all patients and, of these 13 patients, 38.5% (5/13)
      had increased microalbuminuria, 15% (2/13) had increased excretion of RBP and 23%
      (3/13) had increased excretion of IgG. Increased total proteinuria that was not
      detected by testing for microalbuminuria was found in 61.5% (8/13) of patients.
      The youngest patient was 3 years old. Increased microalbuminuria was present in
      25% (8/32) of all patients and was detected as early as 4 years of age. Of these,
      62% (5/8) also had increased total protein excretion and 62% (5/8) also had
      increased IgG excretion. A total of 62.5% were older than 10 years. RBP excretion
      was elevated in 16% (5/32) of patients, all of whom were 7-14 years old. None of
      these patients had increased microalbuminuria or increased excretion of IgG. IgG
      excretion was elevated in 16% (5/32) of patients and was accompanied by increased
      microalbuminuria. All patients with increased IgG excretion were > or = 13 years
      old. We found a weak positive correlation between microalbuminuria and age
      (0.323, P = 0.07). We did not find a significant correlation between any type of
      proteinuria and disease morbidity. Ten of the thirty-two patients received
      hydroxyurea treatment and 60% (6/10) had no proteinuria. Twelve of the thirty-two
      patients received chronic exchange transfusions and 42% (5/12) had no
      proteinuria. CONCLUSION: We found early glomerular selectivity damage in children
      with SCD, which is secondary to both size-selectivity and charge-selectivity
      impairment. Microalbuminuria alone does not adequately detect early renal damage
      in children with SCD. Proximal tubular dysfunction is seen in younger children
      and is independent of glomerular damage. We suggest that children with SCD be
      tested for both total protein and IgG excretion in the urine in addition to
      albumin. Knowing the extent and type of renal damage may allow earlier
      recognition of renal injury and prompt earlier initiation of preventive
      therapies.

PMID- 18065784
TI  - Gene and protein markers of diabetic nephropathy.

PMID- 18065785
TI  - Troponin T is an independent predictor of mortality in renal transplant
      recipients.
AB  - BACKGROUND: Numerous reports have demonstrated an association between elevated
      Troponin T levels and adverse cardiovascular outcomes in patients with chronic
      kidney disease. However, whether raised Troponin T levels are an independent
      predictor of mortality in renal transplant recipients has not yet been
      established. The aim of this study was, therefore, to assess the use of Troponin
      T as a prognostic marker in a population of renal transplant recipients. METHODS:
      Three hundred and seventy-two asymptomatic renal transplant recipients were
      recruited between June 2000 and December 2002. Troponin T was measured at
      baseline and prospective follow-up data were collected at a median of 1739 days.
      RESULTS: In Kaplan-Meier analysis a Troponin T level > or = 0.03 microg/l was a
      significant predictor of mortality (P < 0.001). In Cox Regression analysis, an
      elevated Troponin T level remained a significant predictor of mortality following
      adjustment for traditional cardiovascular risk factors (P < 0.001) and following
      adjustment for estimated glomerular filtration rate and high sensitivity C
      reactive protein (P < 0.001). CONCLUSIONS: Elevated Troponin T level is a strong
      independent predictor of all cause mortality in patients with a renal transplant.
      Troponin T, therefore, represents a promising biochemical marker that identifies
      those renal transplant recipients who are most likely to benefit from aggressive
      cardiovascular risk factor modification.

PMID- 18065786
TI  - Cinacalcet, fetuin-A and interleukin-6.

PMID- 18065787
TI  - Intracellular acidification enhances neutrophil phagocytosis in chronic
      haemodialysis patients: possible role of CD11b/CD18.
AB  - BACKGROUND: We have demonstrated that uraemic neutrophils that exhibit a low
      intracellular pH (pHi) display enhanced phagocytosis. However, the underlying
      cellular mechanism is unclear. METHODS: We used neutrophils from three groups of
      haemodialysis (HD) patients before dialysis (Groups A, B and C) and also from age
      and sex-matched healthy individuals to determine pHi, phagocytosis and
      expression of CD11b, CD18, CD14 and toll-like receptors (TLR)-2 and TLR-4. The
      patients were categorized based on three consecutive monthly pre-dialysis plasma
      bicarbonate concentrations(P(HCO3)) and pH values; Groups A, B and C had a
      constant pre-dialysis P(HCO3) of </=21, 21-26 and >/=26 mmol/L (mEq/L),
      respectively. We also studied the effects induced by the correction of metabolic
      acidosis and monoclonal antibodies (mAbs) against CD11b/CD18 on neutrophils in
      Group A. Furthermore, we investigated the effect of intracellular acidification
      on uraemic neutrophils ex vivo. RESULTS: We observed that the neutrophils in
      Group A exhibited significantly increased phagocytosis and expression of
      CD11b/CD18 compared with those in Groups B and C. Additionally, our ex vivo
      studies demonstrated that the mAbs against CD11b/CD18 partially blocked the
      enhancement of neutrophil phagocytosis in Group A. Moreover, the pHi of uraemic
      neutrophils is inversely correlated with phagocytosis and expression of
      CD11b/CD18. CONCLUSIONS: HD patients with a low P(HCO3) exhibited low neutrophil
      pHi that in turn increased the expression of CD11b/CD18 compared with neutrophils
      with a normal or high pHi. This increased expression of CD11b/CD18 on the uraemic
      neutrophils may contribute to the pHi-mediated phagocytosis.

PMID- 18065788
TI  - Third-generation parathyroid hormone assays and all-cause mortality in incident
      dialysis patients: the CHOICE study.
AB  - BACKGROUND: There has been controversy about the utility of new third-generation
      parathyroid hormone (PTH) assays measuring only 1-84 PTH, with few large studies
      comparing second- and third-generation PTH measurements in patients with ESRD.
      METHODS: We measured 1-84 PTH ('biointact' or 'whole' PTH) and total PTH
      ('intact' PTH) in a national cohort of 515 incident dialysis patients from banked
      frozen EDTA plasma (median follow-up, 35 months) and examined the accuracy of
      estimating 1-84 PTH from total PTH and the associations of these levels with
      patient characteristics and mortality. RESULTS: The 1-84 PTH and total PTH levels
      were closely correlated. Higher 1-84 PTH was associated with African-American
      race and higher serum phosphate and lower calcium levels. The percentage of total
      PTH represented by 1-84 PTH was, on average, 53%, but with a wide range (25-89%).
      Calculating 1-84 PTH from total PTH using a proposed standard conversion factor
      (54%) led to misclassification of 8% of the population compared with measured 1
      84 PTH. In a multivariate Cox proportional hazards model for all-cause mortality,
      a 1-84 PTH value >160 pg/ml was associated with increased risk of mortality (HR =
      1.62, 95% CI, 1.03-2.54) compared to a level of 80-160 pg/ml. Elevated total PTH,
      7-84 PTH and the 1-84 PTH/7-84 PTH ratio were not significantly associated with
      mortality. CONCLUSIONS: The 1-84 PTH and total PTH are highly correlated.
      Elevated 1-84 PTH was significantly associated with increased mortality, whereas
      total PTH did not reach statistical significance. Thus, although in other respect
      they are similar, there may be utility in measuring 1-84 PTH for its associations
      with mortality.

PMID- 18065789
TI  - Preventing haemodialysis catheter-related bacteraemia with an antimicrobial lock
      solution: a meta-analysis of prospective randomized trials.
AB  - BACKGROUND: Catheter-related bacteraemia (CRB) is a major cause of morbidity and
      mortality in haemodialysis patients. Interdialytic locking of catheters with
      antimicrobial agents has recently been investigated for the prevention of CRB. We
      performed a meta-analysis of randomized controlled trials (RCT) to determine the
      efficacy of antimicrobial lock solutions (ALS) in the prevention of CRB in
      haemodialysis patients. METHODS: We collected from Medline, Web of Science, the
      Cochrane Library and major nephrology journals, all relevant references (January
      1990-March 2007). We selected RCT comparing an ALS to a standard heparin lock in
      CRB prevention. We extracted data concerning study quality, patient
      characteristics and CRB incidence. The relative risk (RR) of CRB was calculated
      as Ln (CRB incidence control/CRB incidence experimental) using both a fixed- and
      a random-effects model. RESULTS: Eight studies were included, involving 829
      patients, 882 catheters and 90 191 catheter-days. The use of an ALS significantly
      decreased the risk of CRB (RR 0.32; 95% CI 0.10-0.42). Borderline heterogeneity
      was observed in the fixed-effects model (Q = 14.42; P = 0.071). Despite the under
      representation of small negative studies, the high number of additional trials
      necessary to reverse the final effect strengthens the confidence in the overall
      results. Subgroup analyses stratified by the presence of diabetes, duration of
      follow-up, biochemical markers, proportion of tunnelled cuffed catheters,
      intranasal mupirocin use and citrate use in the ALS did not show significant
      differences, except a higher efficacy of gentamicin-containing lock solutions (P
      = 0.003). CONCLUSIONS: The use of ALS reduces by about a factor 3 the risk of CRB
      in haemodialysis patients. The achieved absolute incidence is similar to the best
      published figures (presumably related to stricter hygienic measures). The limited
      follow-up of the studies does not exclude the onset of adverse events or
      bacterial resistance with longer use of ALS.

PMID- 18065790
TI  - The impact of population-based identification of chronic kidney disease using
      estimated glomerular filtration rate (eGFR) reporting.
AB  - BACKGROUND: The object of this study was to determine the impact of estimated
      glomerular filtration rate (eGFR) reporting, as part of a disease management
      programme (DMP), and clarify the prevalence of chronic kidney disease (CKD) and
      the level of un-met need in a UK Primary Care Trust. METHODS: Our approach was to
      prospectively identify patients with an eGFR <60 ml/min/1.73 m(2) using the four
      variable MDRD equation in all patients from West Lincolnshire PCT (population 185
      434 over the age of 15 years) having a routine estimation of serum creatinine.
      RESULTS: During the first 12 months of the programme 25.4% of the population had
      an eGFR reported. The likelihood of having an eGFR reported increased markedly
      with age. The prevalence of CKD stages 3-5 within primary care was 7.3%. Only
      3.7% of patients with CKD stages 3-5 were under nephrology care compared to 13.7%
      in non-nephrology secondary care and 82.6% in primary care. There were marked
      differences in the male to female ratio between primary care and nephrology care,
      1:1.9 versus 0.6:1, respectively (P < 0.001). The incidence of newly identified
      patients with CKD stages 4 and 5 was 0.16%. Initially there was a marked (up to 7
      fold month on month) rise in nephrology referrals following institution of eGFR
      reporting which was reversed by the introduction of a referral management service
      as part of the DMP. Only 33% of patients with CKD stage 4 or 5, identified from
      within primary care, went on to have a nephrology referral in the subsequent 12
      months compared with 44% and 78% respectively identified from non-nephrology
      secondary care (P < 0.001). CONCLUSIONS: The reporting of the eGFR in association
      with this DMP effectively identified patients with CKD. A referral assessment
      programme can effectively ensure appropriate nephrology referral and avoids
      exceeding the capacity of nephrology services. The vast majority of patients with
      CKD stages 3-5 are cared for within primary care. There are marked gender
      differences in the prevalence of CKD stages 3-5 that are not reflected by
      referral patterns to nephrology services. There are significant differences in
      referral practices between primary and secondary care. In a steady state the
      burden of incident patients with CKD stages 4-5 should not exceed the capacity of
      the local nephrology service.

PMID- 18065791
TI  - Distribution of pathologic findings in individuals with nephrotic proteinuria
      according to serum albumin.
AB  - BACKGROUND: Previous studies of the nephrotic syndrome have not carefully
      examined the relationship between serum albumin and the distribution of
      pathologic diagnoses found at the time of biopsy. The spectrum of pathologic
      findings in individuals with nephrotic proteinuria and a normal serum albumin has
      not been determined. Knowledge regarding the spectrum of findings in nephrotic
      proteinuria according to serum albumin levels may help nephrologists in the
      clinical decision making of when to perform a renal biopsy and in determining
      proper management of these patients. METHODS: Pathologic reports of native kidney
      biopsies performed for idiopathic proteinuria >3 g/24 h were reviewed. Clinical
      characteristics and biopsy findings were compared for individuals with serum
      albumin <30 g/L (Group I), 30 to <35 g/L (Group II) and >/=35 g/L (Group III).
      RESULTS: There were 57 patients in Group I, 20 in Group II and 35 in Group III.
      The proportion of individuals with focal and segmental glomerulosclerosis (FSGS)
      increased according to group: 26% in Group I, 45% in Group II and 74% in Group
      III. Of 35 patients in Group III, 34 had FSGS or advanced nephrosclerosis from
      another cause. Seven of 17 Group III patients with follow-up required dialysis
      after a mean interval of 6 years. Few of these patients received
      immunosuppressive therapy. CONCLUSIONS: As serum albumin increases in the
      nephrotic syndrome, the proportion of patients with FSGS increases. Patients with
      nephrotic proteinuria and a serum albumin >35 g/L suffer from FSGS,
      nephrosclerosis and have poor renal survival. When evaluating nephrotic patients,
      nephrologists should use this knowledge about the spectrum of disease in the
      clinical decision making of when to perform a biopsy and in providing the patient
      more precise information regarding risks, benefits and alternatives of the kidney
      biopsy procedure.

PMID- 18065792
TI  - Influence of low birth weight on minimal change nephrotic syndrome in children,
      including a meta-analysis.
AB  - BACKGROUND: Low birth weight (LBW) has been shown to lead to a low nephron
      endowment with subsequent glomerular hyperfiltration. Additional renal disease
      can therefore be expected to have a more severe course. Minimal change nephrotic
      syndrome (MCNS) is a common chronic illness in childhood. As it is important to
      be able to predict prognosis in MCNS, we set out to study the effect of LBW on
      MCNS in a cohort of patients from our University Medical Center, and performed a
      meta-analysis. METHODS: A retrospective chart review of children with MCNS
      treated at the VU University Medical Center was performed, identifying 55
      patients of whom 4 had LBW. The meta-analysis was performed using Review Manager
      (The Cochrane Collaboration). RESULTS: The meta-analysis consisted of 201
      patients (25 LBW, 176 normal birth weight). More LBW patients were classified as
      steroid resistant [odds ratio (OR) 6.97 (95% confidence interval [CI] 2.02
      24.04), P = 0.002]. The number of relapses per year of follow-up was
      significantly higher in the LBW patients with MCNS [weighted mean difference 0.93
      (95% CI 0.71-1.15) relapse per year, P < 0.0001]. MCNS patients with LBW were
      significantly more likely to be treated with cyclosporine [OR 4.4 (95% CI 1.7
      11.8), P = 0.003] or cytotoxic agents [OR 4.2 (95% CI 1.8-10.2), P = 0.001]
      during the course of their disease, and they had a higher chance of developing
      several complications during the follow-up period, including hypertension.
      CONCLUSIONS: This meta-analysis provides support for an adverse effect of LBW on
      the course and prognosis of MCNS in children, which can aid clinicians and
      parents in assessing the expected clinical course.

PMID- 18065793
TI  - Tissue formation following implantation of cultured elastic chondrocytes for
      treatment of vesicoureteral reflux.

PMID- 18065794
TI  - Smoking behaviour of patients before and after renal transplantation.
AB  - BACKGROUND: Smoking is the most important remediable cardiovascular risk factor,
      and an independent risk factor for the progression of renal diseases. To date,
      only limited information about changes in cigarette-smoking habits before and
      after renal transplantation is available. METHODS: In a comprehensive cross
      sectional single centre study, we analysed smoking habits of patients registered
      on the waiting list for renal transplantation and patients that had received an
      allograft. RESULTS: Of 230 patients (76.1%), 175 on the waiting list and of 264
      allograft recipients (87.5%), 231 were non-smokers at the time of investigation
      (P <0.01). Among the non-smoking waiting list patients, only 71 (30.9%) had never
      smoked, whereas 108 (40.9%) patients of the allograft recipients were never
      smokers. Of former smoking patients, 27.6% (n = 34) had stopped smoking after
      transplantation. Patients <55 years of age and females were more likely to stop
      smoking than patients >55 years of age or males. A data analysis revealed that
      smokers had a significantly lower probability to attain renal transplantation.
      CONCLUSION: We conclude that renal transplantation is a strong incentive for
      patients to stop smoking. Reasons for changes in smoking behaviour after renal
      transplantation may be an intense contact of the patients with their physicians,
      the fear of a premature loss of the transplanted organ with continued smoking and
      the psychological support during post-transplantation patient care.

PMID- 18065795
TI  - Cinacalcet: benefit and cost.

PMID- 18065796
TI  - Patients with complex arrhythmias during and after haemodialysis suffer from
      different regimens of potassium removal.
AB  - BACKGROUND: Although sudden death is one of the most frequent causes of death in
      haemodialysis (HD) patients, the problem of cardiac arrhythmias, the major cause
      of these outcomes, has been little discussed. METHODS: In 30 arrhythmia-prone HD
      patients, we compared the arrhythmogenic effects of two dialysis techniques
      differing in dialysate potassium (K) content. Each patient underwent Acetate-Free
      Biofiltration sessions with constant (2.5 mEq/l) K (AFB) and sessions with
      decreasing intra-HD K (AFBK), according to a crossover single blind design.
      Holter ECG recording and plasma electrolyte measurements were performed during
      each dialysis session. RESULTS: There was a tendency in the whole sample for
      arrhythmia appearance in AFBK to be reduced as compared to AFB throughout the 24
      hr period, although this reduction was not statistically significant. In the
      subset of patients sensitive to dialysis as far as arrhythmia onset is concerned,
      AFBK was systematically less arrhythmogenic than AFB (P < 0.01). The highest
      difference was achieved around the 14th hour after the end of dialysis, when the
      premature ventricular contractions in AFB were 3.9 times higher than in AFBK (P <
      0.05). Potassium kinetics differed between the two procedures. At the first hour
      of treatment, the plasma K concentration was lower in AFB than in AFBK (3.67 +/-
      0.15 mEq/l in AFB vs 4.06 +/- 0.13 mEq/l in AFBK, P = 0.05). CONCLUSIONS: Our
      study shows a greater arrhythmogenic activity with the use of a constant and
      relatively low K concentration as compared to decreasing K profiling in dialysis
      sensitive arrhythmic patients. Smoother K removal may well engender a kind of
      protective effect.

PMID- 18065797
TI  - A spoonful of sugar helps the proteinuria go down?

PMID- 18065798
TI  - Fluoxetine effect on kidney water reabsorption.
AB  - BACKGROUND: The pathogenesis of hyponatraemia caused by fluoxetine(Fx) use in the
      treatment of depression is not well understood. It has been attributed to a
      SIADH, although ADH-enhanced plasma level has not yet been demonstrated in all
      the cases reported in humans. This experiment aimed at investigating the effect
      of fluoxetine on the kidney and more specifically in the inner medullary
      collecting duct (IMCD). METHODS: (1) In vivo study: (a) 10 rats were injected
      daily i.p. with 10 mg/kg fluoxetine doses. After 10 days, rats were sacrificed
      and blood and kidneys were collected. (b) Immunoblotting studies for AQP2 protein
      expression in the IMCD from injected rats and in IMCD tubules suspension from 10
      normal rats incubated with 10(-7) M fluoxetine. (2) In vitro microperfusion
      study: The osmotic water permeability (P(f), mum/s) was determined in normal rats
      IMCD (n = 6), isolated and perfused by the standard methods. RESULTS: In vivo
      study: (a) Injected rats with fluoxetine lost about 12% body weight; Na(+) plasma
      level decreased from 139.3 +/- 0.78 mEq/l to 134.9 +/- 0.5 mEq/l (p < 0.01) and
      K(+) and ADH plasma levels remained unchanged. (b) Immunoblotting densitometric
      analysis of the assays showed an increase in AQP2 protein abundance of about 40%,
      both in IMCDs from injected rats [control period (cont) 99.6 +/- 5.2 versus Fx
      145.6 +/- 16.9, p < 0.05] and in tubule suspension incubated with fluoxetine
      (cont 100.0 +/- 3.5 versus 143.0 +/- 2.0, p < 0.01). In vitro microperfusion
      study fluoxetine increased P(f) in the IMCD in the absence of ADH from the cont
      7.24 +/- 2.07 to Fx 15.77 +/- 3.25 (p < 0.01). CONCLUSION: After fluoxetine use,
      the weight and plasma Na(+) level decreased, and the K(+) and ADH plasma levels
      remained unchanged, whereas the AQP2 protein abundance and water absorption in
      the IMCD increased, leading us to conclude that the direct effect of fluoxetine
      in the IMCD could explain at least in part, the hyponatraemia found sometime
      after this drug use in humans.

PMID- 18065799
TI  - Missense mutations in EYA1 and TCF2 are a rare cause of urinary tract
      malformations.

PMID- 18065800
TI  - Increased serum advanced glycation end products are associated with impairment in
      HDL antioxidative capacity in diabetic nephropathy.
AB  - BACKGROUND: Advanced glycation end products (AGEs) play an important role in the
      pathogenesis of diabetic complications. Recent data suggest that AGEs may also
      interfere with the function of HDL and the reverse cholesterol transport pathway.
      We have investigated whether serum AGE level is associated with impairment in the
      antioxidative capacity of HDL and in the ability of serum to induce cholesterol
      efflux in type 2 diabetic patients with and without nephropathy. METHODS: A total
      of 167 controls and 264 diabetic patients was recruited. The ability of serum to
      induce cellular cholesterol efflux and the capacity of HDL to inhibit LDL
      oxidation ex vivo was determined. Serum AGEs were assayed by competitive ELISA
      using a polyclonal rabbit antisera raised against AGE-RNase. RESULTS: Diabetic
      subjects were subdivided into three groups (normoalbuminuria, microalbuminuria
      and proteinuria). Serum AGEs were significantly increased in diabetic patients
      with microalbuminuria or proteinuria (P < 0.001). Cholesterol efflux was
      significantly decreased in all three groups of diabetic patients compared to
      controls (P < 0.001) whereas the antioxidative capacity of HDL was significantly
      impaired in patients with microalbuminuria or proteinuria (P < 0.01). No
      relationship between serum AGEs and cholesterol efflux was found. However, serum
      AGE concentration was significantly associated with the antioxidative capacity of
      HDL and this was partly due to the adverse effect of AGEs on paraoxonase-1
      activity. CONCLUSION: In type 2 diabetic patients with incipient or overt
      nephropathy, increased serum concentration of AGEs was associated with impairment
      in the antioxidative capacity of HDL. Cholesterol efflux to serum was also
      reduced but was not related to serum AGEs.

PMID- 18065801
TI  - Cognitive outcome following kidney transplantation.
AB  - BACKGROUND: While a handful of studies have assessed cognition in kidney
      transplant (TX) recipients, the neuropsychological presentation of this
      population is not yet clear. Kidney transplantation typically leads to
      improvement of metabolic factors associated with chronic kidney disease (CKD).
      However, comorbid diseases independently linked with cognitive compromise often
      persist, and for this reason, cognitive difficulties may still be present
      following transplantation. METHODS: In this cross-sectional study, we assessed
      cognition in 42 kidney TX recipients, 45 outpatients with pre-dialysis CKD and 49
      healthy controls using measures of verbal learning and memory and executive
      functioning. RESULTS: Findings indicated that TX and CKD patients demonstrated
      significantly worse verbal learning and memory in comparison to controls. While
      both CKD and TX patients exhibited significantly worse performance than controls
      on a response inhibition measure, only CKD patients performed significantly worse
      on a set-shifting task. CONCLUSIONS: Results suggest that, in comparison to
      controls, verbal memory and executive functioning skills are worse in both CKD
      and TX patients. Further research is needed to determine the etiology and extent
      of cognitive compromise, as well as to assess the clinical implications of these
      findings.

PMID- 18065802
TI  - Association between number of months below K/DOQI haemoglobin target and risk of
      hospitalization and death.
AB  - BACKGROUND: A proportion of haemodialysis patients experience periods below
      target haemoglobin levels due to longer time required to reach the target or to
      haemoglobin level variability. We aimed to determine the consequences associated
      with cumulative number of months below target haemoglobin concentrations.
      METHODS: We constructed an incident cohort including patients whose day 91 after
      dialysis initiation fell between 1 January and 31 December 2002. Haemoglobin
      concentration, erythropoiesis-stimulating agent dose, comorbid condition and
      hospitalization data were obtained from Medicare claims. Patients were classified
      by 0, 1, 2 or 3 months with haemoglobin concentration below the K/DOQI target (11
      g/dL). Using an inverse probability weighted marginal structural model to adjust
      for time-varying factors associated with haemoglobin concentration, we determined
      the association between number of months below target and subsequent risk for
      hospitalization and mortality. RESULTS: The final cohort included 54 328 patients
      who met criteria. Those with more months below haemoglobin target were less
      likely to have received intravenous iron. More months below target were
      associated with increased risk of hospitalization (RR 1.70, 95% CI 1.63-1.76) and
      mortality (RR 2.48, 95% CI 2.28-2.69). CONCLUSIONS: Future interventions should
      focus on modifiable factors associated with greater time below target haemoglobin
      concentrations to determine whether altering the time below target can alter the
      risk of hospitalizations or mortality.

PMID- 18065804
TI  - Vaccination and chronic kidney disease.

PMID- 18065803
TI  - Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis
      (IDMS).
AB  - BACKGROUND AND OBJECTIVES: Diffuse mesangial sclerosis (DMS) is a histologically
      distinct variant of nephrotic syndrome (NS) that is characterized by early onset
      and by progression to end-stage kidney disease (ESKD). Besides syndromic DMS,
      isolated (non-syndromic) DMS (IDMS) has been described. The etiology and
      pathogenesis of DMS is not understood. We recently identified by positional
      cloning recessive mutations in the gene PLCE1/NPHS3 as a novel cause of IDMS. We
      demonstrated a role of PLCE1 in glomerulogenesis. Mutations in two other genes
      WT1 and LAMB2 may also cause IDMS. We therefore determine in this study the
      relative frequency of mutations in PLCE1, WT1 or LAMB2 as the cause of IDMS in a
      worldwide cohort. METHODS: We identified 40 children from 35 families with IDMS
      from a worldwide cohort of 1368 children with NS. All the subjects were analyzed
      for mutations in all exons of PLCE1 by multiplex capillary heteroduplex analysis
      and direct sequencing, by direct sequencing of exons 8 and 9 of WT1, and all the
      exons of LAMB2. RESULTS: The median (range) age at onset of NS was 11 (1-72)
      months. We detected truncating mutations in PLCE1 in 10/35 (28.6%) families and
      WT1 mutations in 3/35 (8.5%) families. We found no mutations in LAMB2.
      CONCLUSIONS: PLCE1 mutation is the most common cause of IDMS in this cohort. We
      previously reported that one child with truncating mutation in PLCE1 responded to
      cyclosporine therapy. If this observation is confirmed in a larger study,
      mutations in PLCE1 may serve as a biomarker for selecting patients with IDMS who
      may benefit from treatment.

PMID- 18065805
TI  - The role of C4d immunostaining in the evaluation of the causes of renal allograft
      dysfunction.
AB  - BACKGROUND: Renal biopsy is the gold standard for diagnosis of acute rejection in
      renal transplant recipients. The Banff (1997) classification was revised in 2003
      incorporating morphological criteria and C4d immunostaining for the diagnosis of
      acute antibody-mediated rejection. AIMS: The aim of this study was to evaluate
      the role of histomorphology and C4d immunostaining in indicated renal allograft
      biopsies with a clinical follow-up for a minimum duration of 1 year. MATERIAL AND
      METHODS: Histological analysis and C4d immunostaining were performed on 132
      needle core biopsies and 2 nephrectomy specimens from 107 patients from July 2004
      to June 2005. RESULTS: Histological analysis revealed 59 cases of acute
      rejection, 10 biopsies of acute tubular necrosis, 41 cases of chronic allograft
      nephropathy (CAN), either alone or in combination with other diseases, and 18
      biopsies of normal morphology. There were four cases of BK nephropathy (BK N) and
      eight cases had miscellaneous diagnoses. C4d immunostaining was performed on 126
      biopsies. Overall, the prevalence of C4d positivity was 45% (57 of 126). Fifty
      five percent (28 of 51) of the cases of acute rejection showed C4d positivity
      including 81% of presumptive antibody-mediated rejection (P-AbAR), 20% acute
      cellular rejection and 58% acute cellular rejection + P-AbAR. Overall C4d
      positivity was 37% in chronic allograft nephropathy. Acute tubular necrosis and
      borderline rejection showed 25 and 50% C4d positivity, respectively. Amongst
      various histological features, capillary margination of polymorphs and dilatation
      of peritubular capillaries (PTC-D) showed significant association with C4d
      positivity (P < 0.005). In cases of CAN, transplant glomerulopathy had
      significant association with C4d positivity. C4d-positive cases had a higher mean
      value of serum creatinine at the time of biopsies. CONCLUSION: It is concluded
      that C4d staining is a useful adjunct marker of the humoral limb of rejection,
      both in early and late post-transplant periods.

PMID- 18065806
TI  - The outcome of chronic dialysis in infants and toddlers--advantages and drawbacks
      of haemodialysis.
AB  - BACKGROUND: Improvements in dialysis technology allow replacement therapy for
      even the youngest of children with end stage renal disease. Nevertheless, the
      cumulative experience in this age group is limited. METHODS: We compared the
      outcome of 20 children who initiated chronic dialysis before the age of 1 year
      (weight 4.9 +/- 2 kg, Group 1), with a particular focus on those under the age of
      1 month (eight children, weight 2.9 +/- 0.34), to that of 14 patients, aged 1.1-3
      years when starting dialysis (weight 10.1 +/- 1.7, Group 2). RESULTS: The outcome
      was poor in the youngest age group; only 3/8 survived to 3 years. Of those who
      started dialysis between the ages of 0.3 and 3 years, 84% underwent kidney
      transplantation. One-, three-, five-, and eight-year patient survival was 96%,
      88%, 84% and 84% respectively [corrected] Severe co-morbidities were present in
      almost half of those who died. Hospital stay was 3.5 times longer in Group 1 than
      in Group 2 during the first 3 months of dialysis. Permanent central venous
      catheters inserted under ultrasound guidance resulted in a 4.4-fold increase in
      catheter survival compared to non-cuffed catheters. Marked blood loss at
      beginning of haemodialysis (HD) is attributable to residual volume in the
      dialysis system (15.7 mL/kg/month) and frequent blood tests (12.1 +/- 5.9
      mL/kg/month). These values decreased 2-fold after 8 months of treatment.
      CONCLUSIONS: The main factors determining the poor outcome of infants on dialysis
      are extremely young age at initiation and severe co-morbidities. Despite some
      disadvantages, HD may be successfully implemented in infants and toddlers, in
      highly specialized centres with a well-trained nursing staff.

PMID- 18065807
TI  - Renal disease in HIV-seropositive patients in Nigeria: an assessment of
      prevalence, clinical features and risk factors.
AB  - In order to determine the pattern of renal disease and risk factors for renal
      disease in HIV-infected Nigerians, we studied 400 consecutive HIV/AIDS patients
      (210 males, 190 females) aged between 18 and 65 years (mean +/- SD; 34.6 +/- 9.4
      years), and examined renal disease factors attributable to the infection.
      Diagnosis of renal disease was based on the consistent presence of at least 1+
      albuminuria and/or elevated serum creatinine (>132 micromol/l) as well as the
      absence of other identifiable causes of chronic kidney disease (CKD). We
      determined socio-demography and clinical findings, as well as full laboratory
      work-ups including haemogram, CD4+ cell count, serum electrolytes, urea,
      creatinine, protein, cholesterol and urine analysis. Renal biopsies were taken in
      10 patients who had moderate to massive proteinuria and had consented to the
      procedure. Finally, we compared HIV/AIDS cases with and without renal disease to
      determine the risk factors for nephropathy. We observed a high prevalence of
      renal disease (proteinuria and/or elevated serum creatinine), which was present
      in 152 (38%) of the patients. This subgroup included 74 males and 78 females with
      a M:F ratio of 1:1. The mean age (+/-SD) was 35.8 (+/-10.01) years. Systolic
      and/or diastolic hypertension was seen in 13.2% of these patients while the mean
      (+/- SD) body mass index (BMI) and packed cell volume (PCV) were 18.5 (+/-3.1)
      kg/m(2) and 25.26 (+/-6.81)%, respectively. The mean (+/-SD) CD4+ count was
      246.49 (+/-192.8) cells/microl, while the mean (+/-SD) serum creatinine and 24-h
      urine protein excretion rates were 210.11 (+/-337.8) micromol/l and 2.57 (+/-
      2.42) g/day, respectively. In subjects with and without nephropathy, there were
      significant differences in age, BMI, serum cholesterol, serum albumin and CD4+
      counts, suggesting that these parameters may be risk factors for nephropathy.
      Histology revealed mainly focal glomerulosclerosis (FGS) with glomerular
      collapse. We conclude that the prevalence of proteinuria in HIV-seropositive
      patients is high in Nigeria. Such subjects show an equal male:female
      distribution, and glomerular histology revealed that a majority of biopsied
      patients had the collapsing FSGS variant. The risk factors for renal disease
      included severity of the HIV infection (inferred from the generally low CD4+
      count), anaemia, malnutrition and increasing age.

PMID- 18065809
TI  - Effects of statins on renal sodium and water handling: acute and short-term
      effects of atorvastatin on renal haemodynamics, tubular function, vasoactive
      hormones, blood pressure and pulse rate in healthy, normocholesterolemic humans.
AB  - BACKGROUND: Statins have a beneficial effect on cardiovascular morbidity and
      mortality due to a reduction in plasma cholesterol. However, statins seem to have
      effects beyond the lowering of plasma cholesterol. We hypothesize that these
      effects are caused by an effect on renal function. METHODS: We measured the
      effects of atorvastatin (AS) on renal function in two randomized, placebo
      controlled, double-blinded and crossover studies in healthy man. In an acute
      trial (Study 1), 19 subjects received either 80 mg AS as a single dose or
      placebo. In a short-term trial (Study 2), 20 subjects received either 80 mg AS or
      placebo daily for 4 weeks. In both studies glomerular filtration rate (GFR),
      renal plasma flow (RPF), plasma concentrations of angiotensin II (Ang II), renin
      (PRC), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP),
      aldosterone (Aldo), vasopressin (AVP) and blood pressure (BP) were determined.
      RESULTS: In Study 1 AS decreased fractional excretion of sodium (FE(Na))
      significantly (P = 0.035), but very modestly, and reduced diastolic BP (P =
      0.024). Apart from this, we found no significant differences in GFR, RPF, tubular
      function and vasoactive hormones in either Study 1 or 2. CONCLUSIONS: An acute
      dose of AS decreased FE(Na) and DBP in healthy humans. The reduction in
      fractional urinary sodium excretion was very modest and transitory, and most
      likely secondary to the fall in diastolic blood pressure (DBP). However, renal
      haemodynamics, tubular function, vasoactive hormones and blood pressure were
      unchanged during short-term statin treatment in healthy man.

PMID- 18065810
TI  - Mycophenolate mofetil versus cyclophosphamide for inducing remission of ANCA
      vasculitis with moderate renal involvement.
AB  - OBJECTIVE: We performed a single-centre non-blinded clinical trial to compare the
      clinical efficacies of mycophenolate mofetil (MMF) and intermittent
      cyclophosphamide (CTX) pulse therapy as induction treatments in patients with
      antineutrophil cytoplasmic antibody (ANCA) vasculitis (AAV) and moderate renal
      involvement. METHODS: Patients with active AAV and serum creatinine <500
      micromol/L received either MMF treatment (MMF group) or monthly CTX pulse therapy
      (CTX group) for 6 months. Disease activity was assessed using the Birmingham
      Vasculitis Activity Score (BVAS). The disease activity, remission rate, renal
      function and adverse reactions were compared between the two groups. RESULTS: A
      total of 35 patients (15 male, 20 female: aged 49.1 +/- 12.2 years) were
      enrolled, with 18 in the MMF group and 17 in the CTX group. Of the 35 patients,
      28 were MPO-ANCA positive and 2 were PR3-ANCA positive. Four patients were lost
      to follow-up in the CTX group. At Month 6, BVAS scores were much lower in the MMF
      group than in the CTX group (0.2 +/- 0.89 versus 2.6 +/- 1.7, P < 0.05). In the
      intent-to-treatment analysis, 14 of 18 patients (77.8%) treated with MMF and 8 of
      17 patients receiving CTX (47.1%) had complete remission with an absolute
      difference of 30.7%. Eight of 18 patients (44.4%) in the MMF group and 2 of 17
      patients (15.4%) in the CTX group recovered renal function. Serum ANCA decreased
      to normal in 41.7% of patients in the MMF group and in 16.7% in the CTX group.
      Side effects in the MMF group were pneumonia (1), herpes zoster (1) and
      gastrointestinal symptoms (2), and in the CTX group were leukocytopenia (1),
      gastrointestinal distress (4) and pneumonia (1). CONCLUSION: Our study suggests
      that MMF effectively ameliorates disease activity and considerably improves renal
      function in patients with AAV. Further large-scale multicentre prospective
      randomized controlled trials will be needed to confirm these findings.

PMID- 18065812
TI  - Risk-based surveillance for H5N1 avian influenza virus in wild birds in Great
      Britain.
AB  - Recent outbreaks of the H5N1 strain of avian influenza in Europe have highlighted
      the need for continuous surveillance and early detection to reduce the likelihood
      of a major outbreak in the commercial poultry industry. In Great Britain (gb),
      one possible route by which H5N1 could be introduced into domestic poultry is
      through migratory wild birds from Europe and Asia. Extensive monitoring data on
      the 24 wild bird species considered most likely to introduce the virus into GB,
      and analyses of local poultry populations, were used to develop a risk profile to
      identify the areas where H5N1 is most likely to enter and spread to commercial
      poultry. The results indicate that surveillance would be best focused on areas of
      Norfolk, Suffolk, Lancashire, Lincolnshire, south-west England and the Welsh
      borders, with areas of lower priority in Anglesey, south-west Wales, north-east
      Aberdeenshire and the Firth of Forth area of Scotland. These areas have
      significant poultry populations including a large number of free-range flocks,
      and a high abundance of the 24 wild bird species.

PMID- 18065811
TI  - Tetra- and hexavalent mannosides inhibit the pro-apoptotic, antiproliferative and
      cell surface clustering effects of concanavalin-A: impact on MT1-MMP functions in
      marrow-derived mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSC) mobilization and recruitment by experimental
      vascularizing tumors involves membrane type 1-matrix metalloproteinase (MT1-MMP)
      functions. Given that the mannose-specific lectin Concanavalin-A (ConA) induces
      MT1-MMP expression and mimics biological lectins/carbohydrate interactions, we
      synthesized and tested the potential of 11 mannoside clusters to block ConA
      activities on MSC. We found that tetra- and hexavalent mannosides reversed ConA
      mediated changes in MSC morphology and antagonized ConA-induced caspase-3
      activity and proMMP-2 activation. Tetra- and hexavalent mannosides also inhibited
      ConA- but not the cytoskeleton disrupting agent Cytochalasin-d-induced MT1-MMP
      cell surface proteolytic processing mechanisms, and effects on cell cycle phase
      progression. The antiproliferative and pro-apoptotic impact of ConA on the MT1
      MMP/glucose-6-phosphate transporter signaling axis was also reversed by these
      mannosides. In conclusion, we designed and identified glycocluster constructions
      that efficiently interfered with carbohydrate-binding proteins (lectins)
      interaction with oligosaccharide moieties of glycoproteins at the cell surface of
      MSC. These glycoclusters may serve in carbohydrate-based anticancer strategies
      through their ability to specifically target MT1-MMP pleiotropic functions in
      cell survival, proliferation, and extracellular matrix degradation.

PMID- 18065814
TI  - Myonecrosis in three horses with colic: evidence for endotoxic injury.
AB  - Three horses with colic, clinical evidence of endotoxaemia and high serum
      activities of creatine kinase and aspartate aminotransferase were examined
      postmortem. The horses were diagnosed with severe ulcerative colitis, pyloric
      ulceration and stenosis with colonic sand impaction, and colonic obstruction due
      to faecaliths. There was no gross or histological evidence of muscle trauma.
      Their semimembranosus muscles had scattered acute to subacute segmental necrosis
      of the myofibres, suggestive of endotoxin-induced muscle injury.

PMID- 18065813
TI  - Effect of skin testing and segregation on the prevalence of bovine tuberculosis,
      and molecular typing of Mycobacterium bovis, in Ethiopia.
AB  - In 2002, the prevalence of bovine tuberculosis (tb) among 500 cattle on Holeta
      Farm, near Addis Ababa, Ethiopia, was 48 per cent, and the farm was divided into
      positive and negative herds. After three consecutive rounds of skin testing and
      segregation of skin test-positive and -negative animals, the prevalence of bovine
      tb was reduced from 14 per cent to 1 per cent in the negative herd in a year.
      Spoligotyping of 41 isolates from 17 cows gave an identical and unique
      spoligotype pattern, which can be represented as the binary number
      1100000101111110111111100010000000000100000, where 1 indicates the presence of a
      spacer and 0 represents a loss. This spoligotype pattern had not previously been
      reported on the Mycobacterium bovis spoligotype database, and it was therefore
      designated SB1176, Ethiopian M bovis strain 1 (EMbs1). The variable number tandem
      repeat (VNTR) profile of the strain was 5254(*)33.1, which differed from the VNTR
      profile of strains reported in Great Britain.

PMID- 18065815
TI  - Prevalence of zoonotic nematode species in dogs in Lancashire.

PMID- 18065816
TI  - Management of a distal metaphyseal radial fracture in a dog with a mini T-plate.

PMID- 18065817
TI  - Detection of cyprinid herpesvirus type 3 in goldfish cohabiting with CyHV-3
      infected koi carp (Cyprinus carpio koi).

PMID- 18065818
TI  - RCVS disciplinary procedures.

PMID- 18065820
TI  - ESBL-producing bacteria isolated from companion animals.

PMID- 18065821
TI  - Recognised veterinary practice.

PMID- 18065822
TI  - Owners' perceptions of their dogs.

PMID- 18065823
TI  - Staphylococcal tenosynovitis in pheasants.

PMID- 18065824
TI  - False extended-spectrum beta-lactamase detection in Acinetobacter spp. due to
      intrinsic susceptibility to clavulanic acid.
AB  - BACKGROUND: There are some reports showing the susceptibility of some strains of
      Acinetobacter baumannii to the beta-lactamase inhibitor clavulanic acid. To
      address this issue, we determined the MIC of clavulanic acid for a broad
      collection of Acinetobacter spp. isolates collected in a multicentre study. In
      addition, we showed the consequences of this susceptibility to yield false
      extended-spectrum beta-lactamase (ESBL) detection in this genus. METHODS: The
      strains used were 244 isolates of Acinetobacter (226 A. baumannii, 15
      Acinetobacter genomic species 3 and 3 unidentified Acinetobacter spp.) and
      several A. baumannii as positive controls. The isolates were subjected to
      molecular typing. One isolate of each genotype was subjected to clavulanic acid
      MIC analysis. As no breakpoints for clavulanic acid are available, we arbitrarily
      established three categories of susceptibility: < or = 16, 32-128 and > or = 256
      mg/L. The presence of ESBL in Acinetobacter spp. was analysed by using
      microdilution, double disc diffusion, combined discs, Etest and isoelectric
      focusing. RESULTS: A total of 100 different genotypes were detected. Among them,
      44, 26 and 30 genotypes were inhibited by < or = 16, 32-128 and > or = 256 mg/L
      clavulanic acid, respectively. Representative isolates of each group were tested
      for ESBL production. Only those with the lower clavulanic acid MICs yielded a
      false-positive ESBL test with all methods tested with the exception of the double
      disc diffusion assay. CONCLUSIONS: Forty-four per cent of the genotypes tested
      were inhibited by < or = 16 mg/L clavulanic acid and these Acinetobacter isolates
      yielded a false ESBL-positive test. These results may have implications for
      susceptibility testing in routine microbiology laboratories.

PMID- 18065825
TI  - Rituximab and nephrotic syndrome: a new therapeutic hope?

PMID- 18065826
TI  - Primary care-based disease management of chronic kidney disease (CKD), based on
      estimated glomerular filtration rate (eGFR) reporting, improves patient outcomes.
AB  - BACKGROUND: The majority of patients with chronic kidney disease (CKD) stages 3-5
      are managed within primary care. We describe the effects, on patient outcomes, of
      the introduction of an algorithm-based, primary care disease management programme
      (DMP) for patients with CKD based on automated diagnosis using estimated
      glomerular filtration rate (eGFR) reporting. METHODS: Patients within West
      Lincolnshire Primary Care Trust, UK, population 223, 287 with CKD stage 4 or 5
      were enrolled within the DMP between March 2005 and October 2006. We have
      analysed the performance against clinical targets looking at a change in renal
      function prior to and following joining the DMP and the proportion of patients
      achieving clinical targets for blood pressure control and lipid abnormalities.
      RESULTS: Four hundred and eighty-three patients with CKD stage 4 or 5 were
      enrolled in the programme. There were significant improvements in the following
      parameters, expressed as median values (interquartile range) after 9 months in
      the programme, compared to baseline and percentage values patients achieving
      target at 9 months: total cholesterol 4.2 (3.45-5.0) mmol/l versus 4.6 (3.9-5.4)
      mmol/l (P < 0.01), 75.0% versus 64.5% (P < 0.001); LDL 2.2 (1.6-2.8) mmol/l
      versus 2.5 (1.9-3.2) mmol/l (P < 0.01), 81.9% versus 69.2% (P < 0.05); systolic
      blood pressure 130 (125-145) mmHg versus 139 (124-154) mmHg (P < 0.05), 56.2%
      versus 37.1% (P < 0.05) and diastolic blood pressure 71 (65-79) mmHg versus 76
      (69-84) mmHg (P < 0.01), 68.4% versus 90.3% (P < 0.01). The median fall
      (interquartile range) in eGFR in the 9 months prior to joining the programme was
      3.69 (1.49-7.46) ml/min/1.73 m(2) compared to 0.32 (-2.61-3.12) ml/min/1.73 m(2)
      in the 12 months after enrolment (P < 0.001). One hundred and twenty-two patients
      experienced a fall in eGFR of > or = 5 ml/min/1.73 m(2), median 9.90 (6.55-12.36)
      ml/min/1.73 m(2) in the 9 months prior to joining the programme, whilst in the 12
      months after enrolment, their median fall in eGFR was -1.70 (-6.41-1.64)
      ml/min/1.73 m(2) (P < 0.001). In the remaining patients, the median fall in eGFR
      was 1.92 (0.41-3.23) ml/min/1.73 m(2) prior to joining the programme and 0.86 (
      1.03-3.53) ml/min/1.73 m(2) in the 12 months after enrolment (P = 0.082).
      CONCLUSIONS: These data suggest that chronic disease management in this form is
      an effective method of identifying and managing patients with CKD within the UK.
      The improvement in cardiovascular risk factors and reduction in the rate of
      decline of renal function potentially have significant health benefits for the
      patients and should result in cost savings for the health economy.

PMID- 18065827
TI  - Hypernatraemia in critically ill patients: too little water and too much salt.
AB  - BACKGROUND: Our objective was to study the risk factors and mechanisms of
      hypernatraemia in critically ill patients, a common and potentially serious
      problem. METHODS: In 2005, all patients admitted to the medical, surgical or
      neurological intensive care unit (ICU) of a university hospital were reviewed. A
      1:2 matched case-control study was performed, defining cases as patients who
      developed a serum sodium >/=150 mmol/l in the ICU. RESULTS: One hundred and
      thirty cases with ICU-acquired hypernatraemia (141 +/- 3 to 156 +/- 6 mmol/l)
      were compared to 260 controls. Sepsis (9% versus 2%), hypokalaemia (53% versus
      34%), renal dysfunction (53% versus 13%), hypoalbuminaemia (91% versus 55%), the
      use of mannitol (10% versus 1%) and use of sodium bicarbonate (23% versus 0.4%)
      were more common in cases (P < 0.05 for all) and were independently associated
      with hypernatraemia. During the development of hypernatraemia, fluid balance was
      negative in 80 cases (-31 +/- 2 ml/kg/day), but positive in 50 cases (72 +/- 3
      ml/kg/day). Cases with a positive fluid balance received more sodium plus
      potassium (148 +/- 2 versus 133 +/- 3 mmol/l, P < 0.001). On average, cases were
      polyuric (40 +/- 5 ml/kg). Mortality was higher in cases (48% versus 10%, P <
      0.001), for which hypernatraemia was an independent predictor (odds ratio 4.3,
      95% confidence interval 2.5 to 7.2). CONCLUSIONS: Hypernatraemia seems to develop
      in the ICU because various factors promote renal water loss, which is then
      corrected with too little water or overcorrected with relatively hypertonic
      fluids. Therapy should therefore rely on adding electrolyte-free water and/or
      creating a negative sodium balance. Adjustments in intravenous fluid regimens may
      prevent hypernatraemia.

PMID- 18065828
TI  - Analysis of NO-synthase expression and clinical risk factors in human diabetic
      nephropathy.
AB  - BACKGROUND: Changes of renal nitric oxide (NO) production have been associated
      with glomerular hyperfiltration, vascular permeability, albuminuria,
      glomerulosclerosis and tubulointerstitial fibrosis. Several studies demonstrated
      an up- as well as downregulated expression of NO-synthases (NOS) in experimental
      diabetic nephropathy. It is still not yet specified whether the regulation and
      activity of NOS is changed in human diabetic nephropathy. METHODS: Renal biopsies
      and clinical data of 45 patients with diabetic nephropathy and of 10 control
      subjects were investigated. Glomerular and cortical endothelial NOS (eNOS) and
      inducible NOS (iNOS) expression were assessed by immunohistochemical staining and
      related to clinical data such as the duration of diabetes, insulin therapy and
      arterial hypertension, albuminuria/proteinuria, eGFR according to the formula
      modification of diet in renal disease (MDRD), presence of vascular complications
      or diabetic retinopathy. RESULTS: The mean age of patients at biopsy was 60.3
      years and the mean duration of diabetes 12.9 years. Expression of cortical and
      glomerular eNOS was increased in type 2 diabetes (P < 0.05). Increased expression
      of glomerular and cortical eNOS correlated with more severe vascular
      complications (r = 0.44; P < 0.05). Glomerular eNOS was strongly increased among
      different degrees of proteinuria (P < 0.01). In contrast to expression levels of
      eNOS, the glomerular expression pattern of iNOS changed from an endothelial
      pattern in glomeruli with preserved morphology towards expression predominantly
      by inflammatory cells. CONCLUSIONS: Thus, increased eNOS expression by the renal
      endothelium could be demonstrated in type 2 diabetic nephropathy, whereas iNOS
      was unchanged but spatially differentially expressed. The eNOS expression was
      related to vascular lesions and the degree of proteinuria.

PMID- 18065829
TI  - Resistance exercise augments the acute anabolic effects of intradialytic oral
      nutritional supplementation.
AB  - BACKGROUND: An intriguing strategy to further enhance the anabolic effects of
      nutritional supplementation is to combine the administration of nutrients with
      resistance exercise. We hypothesized that the addition of resistance exercise to
      oral nutrition supplementation would lead to further increases in skeletal muscle
      protein accretion when compared to nutritional supplementation alone in chronic
      haemodialysis (CHD) patients. METHODS: We performed stable isotope protein
      kinetic studies in eight CHD patients during two separate settings: with oral
      nutritional supplementation alone (PO) and oral nutritional supplementation
      combined with a single bout of resistance exercise (PO + EX). Metabolic
      assessment was performed before, during and after haemodialysis. Both
      interventions resulted in robust protein anabolic response. RESULTS: There were
      no differences in metabolic hormones, plasma amino acid and whole-body protein
      balance between the interventions. During the post-HD phase, PO + EX retained a
      positive total amino acid (TAA) balance (primarily due to essential amino acid)
      while PO returned to a negative TAA balance although this difference did not
      reach statistical significance (78 +/- 109 versus -128 +/- 72 nmol/100 ml/min,
      respectively; P = 0.69). In the post-HD phase, PO + EX had significantly higher
      net muscle protein balance when compared to PO (19 +/- 16 versus -24 +/- 10
      microg/100 ml/min, respectively; P = 0.036) We conclude that a single bout of
      resistance exercise augments the protein anabolic effects of oral intradialytic
      nutritional supplementation when examining skeletal muscle protein turnover.

PMID- 18065831
TI  - Cystatin C-based equations: don't repeat the same errors with analytical
      considerations.

PMID- 18065830
TI  - Frequency and severity of acute pancreatitis in chronic dialysis patients.
AB  - BACKGROUND: The incidence and severity of acute pancreatitis in patients
      undergoing dialysis treatment are unknown. METHODS: A questionnaire asking for
      the incidence and the severity of a first attack of acute pancreatitis in chronic
      dialysis patients in the year 2002 was sent to the members of QuaSi-Niere gGmbH,
      an organization representing almost all dialysis centres in Germany. A second
      questionnaire was sent to those who reported such patients. RESULTS: Response
      rates for the first and second questionnaire were 72% (832 out of 1150 centres)
      and 100% (72 out of 72 centres), respectively. After the exclusion of patients
      with invalid data, 55 patients with acute pancreatitis remained: 46 patients out
      of 68 715 haemodialysis (HD) patients (incidence rate 67/100 000/year; 95%
      confidence interval, 49 to 89/100 000/year) and 9 out of 3386 peritoneal dialysis
      (PD) patients (incidence rate 266/100 000/year; 95% confidence interval, 122 to
      504/100 000/year; Fisher's exact test: P = 0.002). Twenty-eight patients (51%)
      had a known risk factor for acute pancreatitis. When these were excluded, the
      incidence of pancreatitis of unknown aetiology was 32/100 000/year (20-48) for HD
      patients (n, 22) and 148/100 000/year (48-345) for PD patients (n, 3; Fisher's
      exact test: P = 0.016). PD patients required hospital admission more frequently
      than HD patients (100% versus 76%) and suffered more frequently from necrotizing
      pancreatitis (50% versus 19%). CONCLUSIONS: Dialysis-especially PD-is another
      risk factor that increases the susceptibility of the pancreas to acute
      pancreatitis. Acute pancreatitis in patients undergoing PD is more frequent and
      seems to be more severe than in those receiving HD treatment.

PMID- 18065832
TI  - Rethinking the history of female circumcision and clitoridectomy: American
      medicine and female sexuality in the late nineteenth century.
AB  - During the late nineteenth and early twentieth centuries, there was one kind of
      female orgasm and it was clitoral; there was also only one kind of healthy sexual
      instinct for a woman and it was for penetrative sex with her husband. When a
      woman behaved outside of this normality-by masturbating or by not responding to
      her husband's affections-her sexual instinct was seen as disordered. If healthy
      women, then, were believed only to be sexual within the marital embrace, what
      better way to explain these errant behaviors than by blaming the clitoris, an
      organ seen as key to female sexual instinct? Doctors corrected a clitoris in an
      unhealthy state using one of four surgeries-removing smegma or adhesions between
      the clitoris and its hood, removing the hood (circumcision), or removing the
      clitoris (clitoridectomy)-in order to correct a woman's sexual instinct in an
      unhealthy state. Their approach to clitoral surgery, at least as revealed in
      published medical works, was a cautious one that respected the importance of
      clitoral stimulation for healthy sexuality while simultaneously recognizing its
      role as cause and symptom in cases of insanity that were tied to masturbation.

PMID- 18065833
TI  - The importance of the accuracy of image registration of SPECT images for 3D
      targeted radionuclide therapy dosimetry.
AB  - In this paper, the importance of the accuracy of image registration of time
      sequential SPECT images for 3D targeted radionuclide therapy dosimetry is
      studied. Image registration of a series of SPECT scans is required to allow the
      computation of the 3D absorbed dose distribution for both tumour sites and normal
      organs. Three simulated 4D datasets, based on patient therapy studies, were
      generated to allow the effect of mis-registration on the absorbed dose
      distribution to be investigated. The tumour sites studied range in size, shape
      and position, relative to the centre of the 3D SPECT scan. Randomly generated
      transformations along the x-, y- and z-axes and rotations around the z-axis were
      employed and the maximum and average absorbed dose distribution statistics, for
      the tumour sites present, were computed. It was shown that even small mis
      registrations, translation of less than 9 mm and rotation of less than 5 degrees
      might cause differences in the absorbed dose statistics of up to 90%, especially
      when the size of the tumour is comparable to the induced mis-registration or when
      the tumour is situated close to the edge of the 3D dataset.

PMID- 18065834
TI  - Electromagnetic modelling of current flow in the heart from TASER devices and the
      risk of cardiac dysrhythmias.
AB  - Increasing use by law enforcement agencies of the M26 and X26 TASER electrical
      incapacitation devices has raised concerns about the arrhythmogenic potential of
      these weapons. Using a numerical phantom constructed from medical images of the
      human body in which the material properties of the tissues are represented,
      computational electromagnetic modelling has been used to predict the currents
      arising at the heart following injection of M26 and X26 waveforms at the anterior
      surface of the chest (with one TASER 'barb' directly overlying the ventricles).
      The modelling indicated that the peak absolute current densities at the
      ventricles were 0.66 and 0.11 mA mm(-2) for the M26 and X26 waveforms,
      respectively. When applied during the vulnerable period to the ventricular
      epicardial surface of guinea-pig isolated hearts, the M26 and X26 waveforms
      induced ectopic beats, but only at current densities greater than 60-fold those
      predicted by the modelling. When applied to the ventricles in trains designed to
      mimic the discharge patterns of the TASER devices, neither waveform induced
      ventricular fibrillation at peak currents >70-fold (for the M26 waveform) and
      >240-fold (for the X26) higher than the modelled current densities. This study
      provides evidence for a lack of arrhythmogenic action of the M26 and X26 TASER
      devices.

PMID- 18065835
TI  - Accelerating IMRT optimization by voxel sampling.
AB  - This paper presents a new method for accelerating intensity-modulated radiation
      therapy (IMRT) optimization using voxel sampling. Rather than calculating the
      dose to the entire patient at each step in the optimization, the dose is only
      calculated for some randomly selected voxels. Those voxels are then used to
      calculate estimates of the objective and gradient which are used in a randomized
      version of a steepest descent algorithm. By selecting different voxels on each
      step, we are able to find an optimal solution to the full problem. We also
      present an algorithm to automatically choose the best sampling rate for each
      structure within the patient during the optimization. Seeking further
      improvements, we experimented with several other gradient-based optimization
      algorithms and found that the delta-bar-delta algorithm performs well despite the
      randomness. Overall, we were able to achieve approximately an order of magnitude
      speedup on our test case as compared to steepest descent.

PMID- 18065836
TI  - Anisotropic conductivity imaging with MREIT using equipotential projection
      algorithm.
AB  - Magnetic resonance electrical impedance tomography (MREIT) combines magnetic flux
      or current density measurements obtained by magnetic resonance imaging (MRI) and
      surface potential measurements to reconstruct images of true conductivity with
      high spatial resolution. Most of the biological tissues have anisotropic
      conductivity; therefore, anisotropy should be taken into account in conductivity
      image reconstruction. Almost all of the MREIT reconstruction algorithms proposed
      to date assume isotropic conductivity distribution. In this study, a novel MREIT
      image reconstruction algorithm is proposed to image anisotropic conductivity.
      Relative anisotropic conductivity values are reconstructed iteratively, using
      only current density measurements without any potential measurement. In order to
      obtain true conductivity values, only either one potential or conductivity
      measurement is sufficient to determine a scaling factor. The proposed technique
      is evaluated on simulated data for isotropic and anisotropic conductivity
      distributions, with and without measurement noise. Simulation results show that
      the images of both anisotropic and isotropic conductivity distributions can be
      reconstructed successfully.

PMID- 18065837
TI  - Hard tissue ablation with a spray-assisted mid-IR laser.
AB  - The objective of this study was to understand the dominant mechanism(s) for
      dental enamel ablation with the application of water spray. A free-running
      Er,Cr:YSGG (yttrium, scandium, gallium, garnet) laser was used to ablate human
      enamel tissue at various radiant exposures. During dental ablation, distilled
      water was sprayed on the sample surface, and these results were compared to
      ablation without a spray (dry ablation). In order to identify dominant ablation
      mechanisms, transient acoustic waves were compared to ablation thresholds and the
      volume of material removed. The ablation profile and depth were measured using
      optical coherence tomography (OCT). Irregular surface modification, charring and
      peripheral cracks were associated with dry ablation, whereas craters for spray
      samples were relatively clean without thermal damage. In spite of a 60% higher
      ablation threshold for spray associated irradiations owing to water absorption,
      acoustic peak pressures were six times higher and ablation volume was up to a
      factor of 2 larger compared to dry ablation. The enhanced pressure and ablation
      performance of the spray-assisted process was the result of rapid water
      vaporization, material ejection with recoil stress, interstitial water explosion
      and possibly liquid-jet formation. With water cooling and abrasive/disruptive
      mechanical effects, the spray ablation can be a safe and efficient modality for
      dental treatment.

PMID- 18065838
TI  - Clinical ion beams: semi-analytical calculation of their quality.
AB  - The aim of this work is to define a simplified semi-analytical beam
      transportation code that can calculate the spatial distribution of projectile
      fragments which are widely distributed in a patient's body during heavy-ion beam
      radiotherapy. In this code, we employed an elemental pencil beam model where the
      spatial distribution of radiation quality for an elemental beam is calculated and
      superposed according to the emittance ellipse of the narrow heavy-ion beam
      determined at the entrance of the target. The radiation quality for an elemental
      beam was calculated using Goldhaber's model of fragment distribution. The
      calculation results were compared with the experimental observations for a mono
      energetic narrow (12)C beam measured at the secondary beam line in HIMAC. Despite
      its simplicity, the developed code could reproduce the experimental results well.

PMID- 18065839
TI  - Noninvasive assessment of the rheological behavior of human organs using
      multifrequency MR elastography: a study of brain and liver viscoelasticity.
AB  - MR elastography (MRE) enables the noninvasive determination of the viscoelastic
      behavior of human internal organs based on their response to oscillatory shear
      stress. An experiment was developed that combines multifrequency shear wave
      actuation with broad-band motion sensitization to extend the dynamic range of a
      single MRE examination. With this strategy, multiple wave images corresponding to
      different driving frequencies are simultaneously received and can be analyzed by
      evaluating the dispersion of the complex modulus over frequency. The technique
      was applied on the brain and liver of five healthy volunteers. Its repeatability
      was tested by four follow-up studies in each volunteer. Five standard rheological
      models (Maxwell, Voigt, Zener, Jeffreys and fractional Zener model) were assessed
      for their ability to reproduce the observed dispersion curves. The three
      parameter Zener model was found to yield the most consistent results with two
      shear moduli mu(1) = 0.84 +/- 0.22 (1.36 +/- 0.31) kPa, mu(2) = 2.03 +/- 0.19
      (1.86 +/- 0.34) kPa and one shear viscosity of eta = 6.7 +/- 1.3 (5.5 +/- 1.6) Pa
      s (interindividual mean +/- SD) in brain (liver) experiments. Significant
      differences between the rheological parameters of brain and liver were found for
      mu(1) and eta (P < 0.05), indicating that human brain is softer and possesses a
      higher viscosity than liver.

PMID- 18065840
TI  - PET monitoring of cancer therapy with 3He and 12C beams: a study with the GEANT4
      toolkit.
AB  - We study the spatial distributions of beta(+)-activity produced by therapeutic
      beams of (3)He and (12)C ions in various tissue-like materials. The calculations
      were performed within a Monte Carlo model for heavy-ion therapy (MCHIT) based on
      the GEANT4 toolkit. The contributions from positron-emitting nuclei with T(1/2) >
      10 s, namely (10,11)C, (13)N, (14,15)O, (17,18)F and (30)P, were calculated and
      compared with experimental data obtained during and after irradiation, where
      available. Positron-emitting nuclei are created by a (12)C beam in fragmentation
      reactions of projectile and target nuclei. This leads to a beta(+)-activity
      profile characterized by a noticeable peak located close to the Bragg peak in the
      corresponding depth-dose distribution. This can be used for dose monitoring in
      carbon-ion therapy of cancer. In contrast, as most of the positron-emitting
      nuclei are produced by a (3)He beam in target fragmentation reactions, the
      calculated total beta(+)-activity during or soon after the irradiation period is
      evenly distributed within the projectile range. However, we predict also the
      presence of (13)N, (14)O, (17,18)F created in charge-transfer reactions by low
      energy (3)He ions close to the end of their range in several tissue-like media.
      The time evolution of beta(+)-activity profiles was investigated for both kinds
      of beams. We found that due to the production of (18)F nuclides the beta(+)
      activity profile measured 2 or 3 h after irradiation with (3)He ions will have a
      distinct peak correlated with the maximum of depth-dose distribution. We also
      found certain advantages of low-energy (3)He beams over low-energy proton beams
      for reliable PET monitoring during particle therapy of shallow-located tumours.
      In this case the distal edge of beta(+)-activity distribution from (17)F nuclei
      clearly marks the range of (3)He in tissues.

PMID- 18065841
TI  - Treatment of near-skull brain tissue with a focused device using shear-mode
      conversion: a numerical study.
AB  - Shear mode transmission through the skull has been previously proposed as a new
      trans-skull propagation technique for noninvasive therapeutic ultrasound (Clement
      2004 J. Acoust. Soc. Am. 115 1356-64). The main advantage of choosing shear over
      longitudinal mode resides on the fact that there is less wavefront distortion
      with the former. In the present study, the regions of the brain suitable for
      shear-mode transmission were established for a simple focused ultrasound device.
      The device consists of a spherically curved transducer that has a focal length of
      10 cm, an aperture between 30 degrees and 60 degrees and operates at 0.74 MHz.
      The regions suitable for shear-mode transmission were determined by the shear
      wave acoustic windows that matched the shape of the device acoustic field. The
      acoustic windows were calculated using segmentation and triangulation of outer
      and inner faces of skull from 3D-MRI head datasets. Nine heads of healthy adults
      were analyzed. The surface considered for the calculations was the head region
      found above the supra-orbital margin. For every inspected point in the brain
      volume, the axis of the device was determined by the vector between this
      inspection point and a point located in the center of the brain. Numerical
      predictions of the acoustic field, where shear-mode conversion through the skull
      was considered, were obtained and compared to the case of water-only conditions.
      The brain tissue that is close to the skull showed suitable acoustic windows for
      shear waves. The central region of the brain seems to be unreachable using shear
      mode. Analysis of the acoustic fields showed a proportional relation between the
      acoustic window for shear mode and the effective degree of focusing. However,
      this relation showed significant differences among specimens. In general, highly
      focused fields were obtained when the acoustic window for shear waves (A(SW))
      intersected more than 67% of the entering acoustic window (A(TX)) of the device.
      The average depth from the inner surface of the skull showing this intersection
      value was 13 +/- 10 mm (mean +/- SD). The differences of the degree of focusing
      observed among patients suggest that the intersection A(SW) intersection A(TX)
      can be used as a preliminary criterion for screening and calculation of the
      acoustic fields should confirm the degree of focusing patient by patient. In
      conclusion, shear waves provide a useful method for trans-cranial focusing in
      regions close to the skull surface.

PMID- 18065842
TI  - An exact approach to direct aperture optimization in IMRT treatment planning.
AB  - We consider the problem of intensity-modulated radiation therapy (IMRT) treatment
      planning using direct aperture optimization. While this problem has been
      relatively well studied in recent years, most approaches employ a heuristic
      approach to the generation of apertures. In contrast, we use an exact approach
      that explicitly formulates the fluence map optimization (FMO) problem as a convex
      optimization problem in terms of all multileaf collimator (MLC) deliverable
      apertures and their associated intensities. However, the number of deliverable
      apertures, and therefore the number of decision variables and constraints in the
      new problem formulation, is typically enormous. To overcome this, we use an
      iterative approach that employs a subproblem whose optimal solution either
      provides a suitable aperture to add to a given pool of allowable apertures or
      concludes that the current solution is optimal. We are able to handle standard
      consecutiveness, interdigitation and connectedness constraints that may be
      imposed by the particular MLC system used, as well as jaws-only delivery. Our
      approach has the additional advantage that it can explicitly account for
      transmission of dose through the part of an aperture that is blocked by the MLC
      system, yielding a more precise assessment of the treatment plan than what is
      possible using a traditional beamlet-based FMO problem. Finally, we develop and
      test two stopping rules that can be used to identify treatment plans of high
      clinical quality that are deliverable very efficiently. Tests on clinical head
      and-neck cancer cases showed the efficacy of our approach, yielding treatment
      plans comparable in quality to plans obtained by the traditional method with a
      reduction of more than 75% in the number of apertures and a reduction of more
      than 50% in beam-on time, with only a modest increase in computational effort.
      The results also show that delivery efficiency is very insensitive to the
      addition of traditional MLC constraints; however, jaws-only treatment requires
      about a doubling in beam-on time and number of apertures used. Finally, we showed
      the importance of accounting for transmission effects when assessing or,
      preferably, optimizing treatment plan quality.

PMID- 18065843
TI  - Quantitative simultaneous In-111/Tc-99m planar imaging in a long-bone infection
      phantom.
AB  - In-111-white-blood-cell and Tc-99m-sulfur-colloid dual-radionuclide imaging are
      frequently utilized in the evaluation of patients with suspected osteomyelitis.
      We have developed a quantitative planar imaging method in which Tc-99m and In-111
      scans are acquired simultaneously in accurate spatial registration. Long, thin
      tubes containing only In-111 or Tc-99m were first imaged in a list mode within a
      water bath inclined with respect to the water surface; from these, 12 energy
      spectra corresponding to different Tc/In ratios were synthesized. Triple-energy
      window (TEW) parameters for scatter and radionuclide crosstalk correction,
      including scatter windows and weights, were optimized using 100 noise
      realizations of each of the spectra (1200 total). A long-bone phantom containing
      a simulated infection site was then imaged in water with five In/Tc ratios; 100
      noise realizations of two conjugate-view images were generated from each
      acquisition (500 total). Two regions of interest (ROIs) were defined, and the
      ratio of In/Tc count ratios in these two ROIs was evaluated with and without the
      TEW scatter correction and geometric mean attenuation compensation. The average
      bias improved from 17.2% to 5.3%, with comparable precision. TEW corrections with
      non-optimized but practical energy windows also improved the bias to 6.4%.
      Compared with subjective visual assessment, quantitation of In-111/Tc-99m ratios
      may improve diagnostic accuracy and could eventually permit grading of
      osteomyelitis.

PMID- 18065844
TI  - Monte Carlo simulations for external neutron dosimetry based on the visible
      Chinese human phantom.
AB  - A group of Monte Carlo simulations has been performed for external neutron
      dosimetry calculation based on a whole-body anatomical model, the visible Chinese
      human (VCH) phantom, which was newly developed from high-resolution cryosectional
      color photographic images of a healthy Chinese adult male cadaver. Physical
      characteristics of the VCH computational phantom that consists of 230 x 120 x 892
      voxels corresponding to an element volume of 2 x 2 x 2 mm(3) are evaluated
      through comparison against a variety of other anthropomorphic models. Organ
      absorbed doses and the effective doses for monoenergic neutron beams ranging from
      10(-9) MeV to 10 GeV under six idealized irradiation geometries (AP, PA, LLAT,
      RLAT, ROT and ISO) were calculated using the Monte Carlo code MCNPX2.5. Absorbed
      dose results for selected organs and the effective doses are presented in the
      form of tables. Dose results are also compared with currently available neutron
      data form ICRP Publication 74 and those of VIP-Man. Anatomical variations between
      different models, as well as their influence on dose distributions, are explored.
      Detailed information derived from the VCH phantom is able to lend quantitative
      references to the widespread application of human computational models in
      radiology.

PMID- 18065845
TI  - Automated detection of exudates for diabetic retinopathy screening.
AB  - Automated image analysis is being widely sought to reduce the workload required
      for grading images resulting from diabetic retinopathy screening programmes. The
      recognition of exudates in retinal images is an important goal for automated
      analysis since these are one of the indicators that the disease has progressed to
      a stage requiring referral to an ophthalmologist. Candidate exudates were
      detected using a multi-scale morphological process. Based on local properties,
      the likelihoods of a candidate being a member of classes exudate, drusen or
      background were determined. This leads to a likelihood of the image containing
      exudates which can be thresholded to create a binary decision. Compared to a
      clinical reference standard, images containing exudates were detected with
      sensitivity 95.0% and specificity 84.6% in a test set of 13,219 images of which
      300 contained exudates. Depending on requirements, this method could form part of
      an automated system to detect images showing either any diabetic retinopathy or
      referable diabetic retinopathy.

PMID- 18065846
TI  - 18F-labeled resin microspheres as surrogates for 90Y resin microspheres used in
      the treatment of hepatic tumors: a radiolabeling and PET validation study.
AB  - (90)Y-labeled resin microspheres (SIR-Spheres) are currently used to treat
      patients with primary and metastatic solid liver tumors. This treatment is
      typically palliative since patients have exhausted all other standard treatment
      options. Improving the quality of life and extending patient survival are typical
      benchmarks for tracking patient response. However, the current method for
      predicting microsphere biodistributions with (99m)Tc-labeled macroaggregated
      albumin (MAA) does not correlate well with patient response. This work presents
      the development of a new (18)F-labeled resin microsphere to serve as a surrogate
      for the treatment microsphere and to employ the superior resolution and
      sensitivity of positron emission tomography (PET). The (18)F microsphere
      biodistributions were determined in a rabbit using PET imaging and histological
      review. The PET-based uptake ratio was shown to agree with the histological
      findings to better than 3%. In addition, the radiolabeling process was shown to
      be rapid, efficient and relatively stable in vivo.

PMID- 18065847
TI  - Improvement of dose distribution by central beam shielding in boron neutron
      capture therapy.
AB  - Since boron neutron capture therapy (BNCT) with epithermal neutron beams started
      at the Kyoto University Reactor (KUR) in June 2002, nearly 200 BNCT treatments
      have been carried out. The epithermal neutron irradiation significantly improves
      the dose distribution, compared with the previous irradiation mainly using
      thermal neutrons. However, the treatable depth limit still remains. One effective
      technique to improve the limit is the central shield method. Simulations were
      performed for the incident neutron energies and the annular components of the
      neutron source. It was clear that thermal neutron flux distribution could be
      improved by decreasing the lower energy neutron component and the inner annular
      component of the incident beam. It was found that a central shield of 4-6 cm
      diameter and 10 mm thickness is effective for the 12 cm diameter irradiation
      field. In BNCT at KUR, the depth dose distribution can be much improved by the
      central shield method, resulting in a relative increase of the dose at 8 cm depth
      by about 30%. In addition to the depth dose distribution, the depth dose profile
      is also improved. As the dose rate in the central area is reduced by the
      additional shielding, the necessary irradiation time, however, increases by about
      30% compared to normal treatment.

PMID- 18065848
TI  - Health disparities across the cancer continuum.

PMID- 18065849
TI  - Unsung heroes: Mr. Frank Jackson and Dr. Richard Bragg.

PMID- 18065850
TI  - Racialized geography, corporate activity, and health disparities: tobacco
      industry targeting of inner cities.
AB  - Industry has played a complex role in the rise of tobacco-related diseases in the
      United States. The tobacco industry's activities, including targeted marketing,
      are arguably among the most powerful corporate influences on health and health
      policy. We analyzed over 400 internal tobacco industry documents to explore how,
      during the past several decades, the industry targeted inner cities populated
      predominantly by low-income African American residents with highly concentrated
      menthol cigarette marketing. We study how major tobacco companies competed
      against one another in menthol wars fought within these urban cores. Little
      previous work has analyzed the way in which the inner city's complex geography of
      race, class, and place shaped the avenues used by tobacco corporations to
      increase tobacco use in low-income, predominantly African American urban cores in
      the 1970s-1990s. Our analysis shows how the industry's activities contributed to
      the racialized geography of today's tobacco-related health disparities.

PMID- 18065851
TI  - Long-term engagement in smoking cessation counseling among rural smokers.
AB  - INTRODUCTION: Effective smoking cessation treatment requires active patient
      engagement. This may be particularly important for rural smokers who have less
      access to smoking cessation resources than others. This study describes long-term
      engagement in counseling for smoking cessation and factors associated with
      engagement. METHODS: As part of a randomized trial, 231 rural smokers received up
      to 6 telephone-based counseling sessions at 6-month intervals over 24 months.
      Engagement in treatment was categorized according to the number of counseling
      calls each interval. During the final 6-month interval, more than 60% of
      continuing smokers remained engaged in treatment. Call completion varied over
      time; while levels of engagement dropped after the first interval, many
      continuing smokers remained engaged throughout the study. Education, age,
      motivation, income, diabetes, and health insurance status were predictors of
      treatment engagement. CONCLUSION: This study demonstrates that smokers will
      remain engaged in long-term counseling designed to address the chronic nature of
      nicotine dependence.

PMID- 18065852
TI  - Employment characteristics and socioeconomic factors associated with disparities
      in smoking abstinence and former smoking among U.S. workers.
AB  - PURPOSE: This study examines the associations among employment and socioeconomic
      factors and the outcomes, current smoking, cigarette abstinence and former
      smoking among adult U.S. workers ages 18-64 (n=288,813). METHODS: Multivariate
      logistic regression was used to examine the associations among the variables
      using cross-sectional data from the 1998-1999 and 2001-2002 Tobacco Use
      Supplements to the Current Population Survey. RESULTS: Lower odds of current
      smoking was observed among part-time workers compared to those working variable
      hours and multiple job holders compared to persons holding one job. The self
      employed, part-time workers and multiple job holders had higher odds of former
      smoking than comparison groups. Employment factors were not associated with short
      term abstinence or 12-month abstinence from smoking, but income, education,
      marital status, and duration of smoking were associated with 12-month abstinence.
      CONCLUSIONS: These data suggest that while employment factors are associated with
      current and former smoking, socioeconomic factors are associated with long-term
      quitting.

PMID- 18065853
TI  - A structural approach to examining prostate cancer risk for rural southern
      African American men.
AB  - Physical, cultural, and social factors influence health risk and behavior, but
      few have explored how the environmental context affects African American men's
      prostate cancer screening and treatment. This paper describes a structural
      analysis of data from eight focus groups of rural, southern African American men
      (n=66). A structural approach highlights the interrelationships between
      individuals, the health service system, and community factors that directly and
      indirectly affect screening and treatment for prostate cancer. The availability
      of accurate and timely health information and health services, social norms
      regarding health and professional help-seeking, and the sociopolitical context
      shaped men's screening and treatment behaviors. These proximal and distal health
      factors affected men's prostate cancer knowledge, perceived risk, willingness to
      seek care and trust in the health service system. The findings suggest that
      prostate cancer screening and treatment occurs in a larger structural context
      that has important implications for help-seeking and health promotion.

PMID- 18065854
TI  - Mammography use in the Southern Community Cohort Study (United States).
AB  - PURPOSE: This paper examines the rates of recent mammography use among African
      American and White women, the influence of demographic characteristics,
      socioeconomic status, health insurance coverage, and breast cancer risk factors
      on recent mammography use and reasons for not having a mammogram. METHODS: Cross
      sectional data from the Southern Community Cohort Study were used to analyze
      mammography use among African American and White women. RESULTS: Among 27,123
      mostly low-income women age 42-79 in the Southern Community Cohort Study, the
      rate of recent (within the past 2 years) mammography use was 73% among African
      Americans and 68% among Whites. Health insurance coverage, age, household income,
      education, family history of breast cancer, hormone replacement therapy use, and
      post-menopausal status were positively associated with recent mammography,
      whereas consumption of 2 or more alcoholic drinks/day was negatively associated.
      These associations were observed in both African American and White women who had
      never [corrected] received a mammogram (Non-users) compared with recent
      mammography users, although some variation existed [corrected] Doctor has not
      recommended this test and cost were the two most commonly self-reported reasons
      for non-use. CONCLUSIONS: Characteristics of non-users and past users identified
      may provide valuable information for maintaining the progress made and for
      further improving adherence to the screening guidelines.

PMID- 18065855
TI  - Complementary and alternative medicine for pain management in U.S.- and foreign
      born Chinese women with breast cancer.
AB  - This study explores beliefs about complementary and alternative medicine (CAM)
      use for pain management among 15 U.S.-born and 15 foreign-born Chinese women with
      breast cancer. For this investigation, trilingual interviewers conducted
      individual, face-to-face, qualitative interviews in Cantonese, Mandarin, or
      English. All study participants lived in San Francisco, and the foreign-born
      women had resided in the U.S. for 15 years or fewer. Findings indicate that many
      participants consider CAM a viable method of pain management. However, concerns
      about affordability and quality of treatment prevent some women from using CAM on
      a regular basis. Many participants indicated that Western health care providers
      are poorly equipped to provide CAM to manage the pain resulting from breast
      cancer treatment. Future research should explore how access to CAM can be
      improved for poor and uninsured patients with cancer and how alternative
      approaches to pain management can be integrated more broadly in the U.S. health
      care system.

PMID- 18065856
TI  - Breast cancer among Hispanic and non-Hispanic White women in Arizona.
AB  - BACKGROUND: Breast cancer in Hispanic women is poorly understood and data on
      tumor hormone receptor status in this population are limited. METHODS: Using data
      from the Arizona Cancer Registry, we assessed differences in tumor
      characteristics between Hispanic and non-Hispanic White (NHW) women using
      logistic regression modeling. 25,494 invasive breast cancer cases (23,657 NHWs
      and 1,837 Hispanics) reported to the cancer registry in 1995 to 2003 were
      included in the analysis. RESULTS: In age-adjusted models, compared with NHW
      women, Hispanics were more likely to have high-grade cancers, larger tumors, a
      greater number of positive lymph nodes, and advanced stage at diagnosis. Hispanic
      women were less likely to have tumors that are both estrogen and progesterone
      receptor positive (ER+/PR+), particularly those under age 60. CONCLUSIONS: The
      profile of tumor presentation in Hispanic women in Arizona is consistent with a
      more aggressive disease pattern and less favorable prognosis than that of NHWs.

PMID- 18065857
TI  - Demographic, behavioral, psychosocial, and dietary correlates of cancer screening
      in African Americans.
AB  - PURPOSE: We examined demographic, behavioral, psychosocial, and dietary
      correlates of prostate, breast, and colorectal cancer screening in a population
      based sample of African Americans in North Carolina (n=405). METHODS: Cross
      sectional data of African Americans in North Carolina were analyzed using linear
      regression models. RESULTS: Seventy-eight percent of men had obtained prostate
      screening (PSA test) and 81% of women had received breast cancer screening
      (mammogram) during the previous two years. Screening rates for CRC were lower
      (48% women, 31% men in the previous ten years). Older age, college education, and
      being married were associated with all screening modalities, as was belief in a
      diet-cancer relationship with PSA testing and mammography. There were
      correlations of former smoking, obesity, and healthy eating self-efficacy with
      PSA testing, and family/personal cancer history with CRC screening. Screening for
      all cancers was associated with lower fat consumption, and PSA testing with high
      fruit/vegetable intake (p<.05). CONCLUSIONS: Cancer screening was prevalent, but
      rates did not approach national targets. Knowledge of these correlates can be
      used to design effective cancer screening interventions for African Americans.

PMID- 18065858
TI  - Perceptions of environmental health risks and communication barriers among low
      SEP and racial/ethnic minority communities.
AB  - Despite a disproportionate burden of environmental hazards in lower socioeconomic
      positions (SEP) and racial/ethnic minority communities, research suggests that
      such communities may have concerns about environmental risks different from those
      of their higher SEP and White counterparts. These groups also face
      disproportionate barriers to accessing and utilizing public health information.
      Little work has focused on the environmental risk communication barriers that low
      SEP minorities face. This paper reports on the results of seven focus groups
      conducted in three low-SEP Massachusetts communities, with an over-sample of
      racial/ethnic minorities. We explored (1) definitions of the environment, (2)
      perceptions of environmental health effects, (3) information-seeking behaviors
      around these issues, and (4) challenges to accessing and utilizing information.
      The local environment shapes these communities' perceptions of environmental
      risks; they face considerable barriers to accessing, understanding, and utilizing
      other sources of information about environmental health risks. We discuss the
      implications for future targeted campaigns to reduce negative impacts of
      environmental health risks.

PMID- 18065859
TI  - Network analysis of an organizational collaboration for Pacific Islander cancer
      control.
AB  - Community-based participatory research (CPBR) represents a growing research
      approach for addressing health disparities disfavoring members of racial/ethnic
      minorities and other underserved populations in the U.S. While such endeavors are
      often guided by explicit principles regarding the relationships between
      communities and universities, few studies have reported on the development or
      strength of such relationships. This paper describes the methods and preliminary
      results of a cross-sectional analysis of the ties between community and
      university organizations in a CBPR network to address cancer disparities between
      Pacific Islanders in Southern California and the general population. These
      analyses afford a means of representing the collaborative relationships and may
      enhance tracking improvements in CBPR links for cancer education, research, and
      training. Such tracking will help concerned parties understand how academic and
      community groups collaborate and coordinate their efforts to reach shared and
      overlapping goals.

PMID- 18065860
TI  - Questionnaire design from a cross-cultural perspective: an empirical
      investigation of Koreans and non-Koreans.
AB  - A persistent challenge to self-report data across racial, ethnic, or cultural
      groups is the inherent difficulty of attaining cross-cultural comparability of
      key measures. The current research study investigated the cross-cultural
      functioning of health-survey questions presented to four groups: (1) Koreans who
      were monolingual in Korean; (2) non-Korean native speakers of English; (3)
      bilingual Koreans interviewed in English, and (4) bilingual Koreans interviewed
      in Korean. This design allowed us to include those likely to be medically
      underserved, and to assess both linguistic and cultural barriers to collecting
      health survey data. A total of 36 cognitive interviews were conducted to identify
      (a) translation problems; (b) problems of cultural adaptation that impede cross
      cultural comparability; and (c) generic problems of questionnaire design that
      affect all groups. An important category of problems was identified that appeared
      to result from the interaction of respondent and question characteristics. Such
      problems can best be assessed through explicit consideration of the socio
      cultural backgrounds of survey respondents, as opposed to the more usual focus on
      details of item translation and wording.

PMID- 18065861
TI  - Influence of a standard electropalatography artificial palate upon articulation.
      A preliminary study.
AB  - OBJECTIVE: This study investigated the influence of a standard
      electropalatography (EPG) palate upon speech articulation in 3 normal speakers
      under standard EPG testing conditions. PATIENTS AND METHODS: Three adult females
      aged 26, 31 and 34 years read the experimental phrase 'say CV again' 5 times
      under 3 experimental conditions: normal speech (without a palate in situ), 45 min
      after EPG palate insertion and 3 h after EPG palate insertion. Consonants and
      vowels commonly used in EPG research were studied and included /t/, /s/ and
      /integral/ in the /i/, /a/ and /u/ vowel environments. Perceptual and acoustic
      analysis of the data was completed. RESULTS: The results revealed varied patterns
      of adaptation across the 3 participants. Perceptual analysis suggested that 2 of
      the participants adapted to the presence of the palate; however, 1 did not. The
      presence of the palate resulted in significant changes to consonant duration for
      all 3 participants. Spectrally, production of /t/ was unaffected by the presence
      of the palate, while articulation of fricatives varied across the participants.
      CONCLUSION: Paired with a previous study examining the effects of an EPG palate
      upon speech articulation [McLeod S, Searl J: Am J Speech Lang Pathol 2006;15:192
      206], the present data suggest that researchers and clinicians alike should be
      aware of the potential perturbing effects of the palate.

PMID- 18065862
TI  - [Can the postoperative pain level be predicted preoperatively?].
AB  - PURPOSE OF THE STUDY: We searched for factors present preoperatively which could
      be used to predict the intensity of postoperative pain. MATERIAL AND METHODS: We
      undertook a prospective study among all patients aged over 18 years who underwent
      shoulder surgery from January to September 2004 in our unit. The study included
      86 patients for which the following data were noted preoperatively: past history
      of pain, intensity and duration of prior pain, triggering factors, localization,
      psychological context. The intensity of the postoperative pain was measured on a
      visual analog scale (VAS); measurements were noted up to 24 hours postop then at
      one month. Data processing was performed with Statview5.5. RESULTS: Significant
      postoperative pain was correlated with a prior history of surgical pain, with
      duration of prior pain, with intensity of preoperative pain, and with depression.
      DISCUSSION: Significant sustained preoperative pain can favor memory of pain
      leading to postoperative sensitivization of nociception neurons. Intense
      postoperative pain can favor the development of refractory chronic pain.
      CONCLUSION: Significant postoperative pain can be expected in the following
      situations: pain after prior surgery, presence of chronic pain sustained for more
      than six months, intense preoperative pain, state of depression.

PMID- 18065863
TI  - [Rating of tumoral growth in non-operated primary or recurrent extra-abdominal
      aggressive fibromatosis].
AB  - PURPOSE OF THE STUDY: Extra-abdominal aggressive fibromatosis (EAAF) is a benign
      desmoid tumor with a potentially aggressive behavior. Surgical treatment is
      compromised by a very high rate of recurrence, sometimes with significant
      morbidity. We conducted a prospective surveillance of our patients (clinical and
      MRI) with EAAF to search for prognostic factors. MATERIAL AND METHODS: This
      cohort included 17 patients with EAAF. For nine patients, biopsy alone was
      performed. For eight, the tumor was a recurrence after surgical removal. Patients
      were seen for a clinical assessment and MRI every six months. RESULTS: Median
      follow-up was 42 months (range 6-114). Three patients worsened clinically with
      pain or functional impairment. One patient required neurosurgery to control pain
      (good stable outcome). MRI showed progression for two tumors (12%) but with a
      short follow-up since diagnosis (9 and 14 months), in one case despite medical
      treatment. Three tumors regressed and twelve remained stable on successive MRI.
      On average the tumor growth lasted ten months. DISCUSSION: Tumor growth was never
      noted beyond 36 months. This notion of an interruption in tumor growth is
      mentioned sporadically in reports on EAAF, which have generally included
      recurrent tumors. To our knowledge this is the first series reporting tumors left
      in place a followed with modern imaging techniques. The high rate of spontaneous
      interruption of tumor growth must be counterbalanced with the difficult task of
      local treatment: the risk of recurrence is particularly high after surgery and
      functional sequelae can be significant when wide resection is proposed in an
      anatomically difficult localization. The precise role for surgery, and combined
      radiotherapy, remain to be determined. There are only scarce reports on general
      treatments. Considering these facts, we propose that surgical resection should
      not be considered the only solution for the treatment of EAAF. Further work is
      needed to define the useful contribution of simple surveillance of these benign
      tumors.

PMID- 18065864
TI  - [Reconstruction of long bone defects with a vascularized fibular graft after
      tumor resection in children and adolescents: thirteen cases with 50-month follow
      up].
AB  - PURPOSE OF THE STUDY: The vascularized fibular graft is a widely used technique
      for the reconstruction of long bone defects after tumor resection. Complications
      are not uncommon despite the presence of a good vascular supply. We report our
      experience with long bone reconstructions in children and adolescents after
      resection of primary malignant bone tumors. MATERIAL AND METHODS: This
      retrospective analysis included thirteen patients aged 4-17 years (mean age 12
      years). Preoperatively, the pathological diagnosis was Ewing tumor (n=7),
      osteogenic sarcoma (n=5), neuroepithelioma (n=1). All patients except one were
      given chemotherapy preoperatively and postoperatively and four received adjuvant
      radiotherapy. Tumor resection created a gap (n=8) or involved resection
      arthrodesis (n=5, three knees, one ankle, one elbow). All reconstructions used a
      vascularized fibular flap with a complementary corticocancellous autograft for
      seven. RESULTS: Complete carcinological resection was achieved in all cases. Mean
      follow-up was 50 months (range 12-144 months). There were no cases of local
      recurrence. Three patients presented lung metastasis; two patients died. Eleven
      of the twelve patients who underwent tumor resection involving the lower limb
      were able to walk with full weight bearing at 13.9 months (range 841 months),
      half of them without any supportive device. The MSTS score was 21/30 (range 7
      29). Both ends healed for eleven of thirteen grafts. Outcome was good in four
      cases at 7.7 months (range 6-11), fair in seven (with 1-5 complementary
      procedures) at 14.8 months (range 10-45) and poor in two (nonunion at last follow
      up). Among the fibular grafts which healed, primary healing of the distal end was
      noted in all cases, but not for the proximal end. Significant transplant
      hypertrophy was noted in 62% of patients, measured at mean 77.1% (range 25-128%).
      Complications were: skin necrosis (n=2), nonunion (n=4, three aseptic and one
      septic), disassembly (n=3 with two transplant fractures), and spontaneous
      fracture which healed (n=5, all but one treated orthopedically). There were four
      donor site complications: retraction of the hallux flexor (n=3), regressive
      paresia of the common fibular nerve (n=1). DISCUSSION: The rate of healing in
      this series was similar to earlier reports. Healing was always achieved for the
      distal focus but not for the proximal focus which receives its blood supply from
      a branch of the anterior tibial artery which is not harvested. The defective
      blood supply can thus hinder bone healing. It is necessary to spare the proximal
      quarter of the fibula or harvest a bipediculated graft. The rate of graft
      hypertrophy was also similar, as was the rate of complications. The MSTS score
      was lower due to the poor results obtained with resection-arthrodesis of the knee
      joint. Graft fractures and aseptic nonunion are the most common complications but
      septic complications are more serious and can threaten graft survival.
      Complications at the donor site are exceptional. CONCLUSION: Long bone
      reconstruction using an autologous vascularized fibular graft is a reliable
      technique providing satisfactory functional results. Complications can be
      prevented by making solid fixation and using a corticocancellous graft creating a
      favorable osteoinducing environment. A massive allograft is another solution
      providing good immediate mechanical stability.

PMID- 18065865
TI  - [The long Telegraph nail for humeral fractures].
AB  - PURPOSE OF THE STUDY: We present an anterograde nailing system for humeral shaft
      fractures: the long Telegraph(R) nail. This nail enables static or dynamic
      anteroposterior distal locking and is easy to insert with the special aiming
      device. MATERIAL AND METHOD: This study concerned 148 patients who underwent
      surgery between September 1998 and February 2005, 86 women, men age 68 years and
      62 men, mean age 53 years. After excluding patients lost to follow-up and
      pathological fractures, we analyzed 104 files to determine the rate of nonunion
      as a function of distal locking or not and dynamic versus static locking. We also
      reviewed 56 patients measuring the Constant score at mean 2.7 years follow-up.
      RESULTS: There were no cases of iatrogenic radial palsy and no cases of
      infection. There were four cases of nail fracture. The overall rate of nonunion
      was 7.7%. Nonunion was never observed with dynamic distal locking (p=0.03).
      Regarding the effect of the nail on shoulder function, the mean weighted Constant
      score was 105.4% with preservation of mean joint motion and a pain free shoulder
      in 36/56 patients. DISCUSSION: The long Telegraph(R) nail enables anterograde
      nailing of the humeral shaft with a simplified system for dynamic or static
      distal locking. In this series, dynamic distal locking appeared to provide the
      best rate of nonunion. If installed correctly, the system does not appear to
      affect shoulder function.

PMID- 18065866
TI  - [Acromelic arthritis: a new entity].
AB  - PURPOSE OF THE STUDY: Few patients with rheumatoid arthritis present isolated
      acromelic bone and joint destructions. Concerned joints are wrist, MP, PIP, DIP
      and forefoot. The aim of the current study is to describe and evaluate the long
      term results of wrist, hand and forefoot surgery in an acromelic arthritis group.
      MATERIAL AND METHODS: 93 patients with acromelic arthritis were included in the
      study. 202 surgical procedures were performed between 1981 and 2001 in addition
      to medical treatment. 93 procedures concerned dorsal wrist surgery. The mean
      follow-up of this group was 7 years (24 months-20 years). 78 synovectomies of
      radio-carpal and medio-carpal joints with a Sauve-Kapandji procedure were
      performed and 10 with a radio-lunate arthrodesis and 5 with other surgeries. The
      main indication for surgery was severe pain. RESULTS: Functional results and
      radiographic evolution (Larsen X-ray classification) were studied. All patients
      were satisfied or very satisfied and pain was significantly reduced. Radiographic
      lesions progressed but Larsen's stage remained unchanged in 73% of patients. All
      patients with forefoot surgery recovered total walk autonomy. DISCUSSION:
      Acromelic arthritis is a particular form of rheumatoid arthritis that progresses
      very slowly. Surgery should be indicated earlier, for a better joint function
      stabilisation.

PMID- 18065867
TI  - [Surgical site infection after total knee arthroplasty: a monocenter analysis of
      923 first-intention implantations].
AB  - PURPOSE OF THE STUDY: We report the results of a retrospective analysis of 923
      cases of first-intention total knee arthroplasties. The objective was to
      determine retrospectively the rate of surgical site infections, including all
      infections diagnosed during the first year, and to search for risk factors. We
      also wanted to present our surveillance system planned for a 10-year period.
      MATERIAL AND METHODS: From January 1994 to January 2004, first-intention total
      knee arthroplasty (TKA) was performed on 999 knees. HLS prostheses were
      implanted. At minimum 12 months, follow-up data was complete for 923 implants
      which constituted the study group. Female gender predominated (72%). Mean patient
      was 71 years (range 26-93). Anterior surgery was performed for 25% of the knees.
      Etiologies were osteoarthritis (87.5%), and rheumatoid polyarthritis (6.9%).
      Cefazolin was used for systematic preoperative (one injection) and postoperative
      (48 hr) antibiotic proxphylaxis. Vancomycin was used for patients with a
      contraindication for cefazolin. Information was collected from two sources:
      computerized consultation charts for all follow-up visits completed prospectively
      since 1995 et data collected by the Hygiene and Epidemiology Unit during the year
      following implantation. Data on surgical site infections was collected from the
      hospitalization files, outpatient files and control visits. Each case of
      infection was validated at an annual interdisciplinary meeting. We retained for
      analysis deep infections requiring revision surgery with identification of the
      causal agent on the intraoperative samples. We identified a subgroup of
      infections occurring during the first postoperative year, the delay generally
      retained for surgical site infections. RESULTS: Twenty surgical site infections
      after TKA were identified during the 10-year surveillance period (2.1%). Mean
      follow-up was 43 months (range 12-123 months, median 37 months). The rate of
      surgical site infections occurring during the first postoperative year was 1.4%.
      Eighty-percent of the infections (n=16) occurred within the first two
      postoperative months. Two infections were diagnosed two to five years after
      surgery and two others more than five years after surgery due to hematogenous
      contamination. All of the observed infections involved a single causal germ.
      Agents identified were: Gram+ (90%) and Gram- (10%), with a clear predominance
      for Staphylococcus aureus (n=9). Infections developed 2.1-fold more often in
      patients with an inflammatory disease (rheumatoid polyarthritis). Age and body
      mass index did not differ between patients with and without surgical site
      infection. CONCLUSION: The analysis of our series demonstrated the difficulties
      in conducting long-term surveillance.

PMID- 18065868
TI  - [Open-wedge retro-tubercular tibial osteotomy: an innovating technique].
AB  - Open-wedge tibial osteotomy for varus correction is a common orthopedic
      procedure. The rate of complications remains significant: loss of correction,
      nonunion, patellar infera... We propose a new open-wedge technique for tibial
      osteotomy which has several advantages: less risk of patella infera, improved
      bone healing, excellent mechanical stability. The osteotomy involves two cuts
      with an anterior portion ending distally to the tibial tubercle. This preserves
      the integrity of the patellar tendon and maintains contact between the proximal
      tibia and the tibial tubercle. Adjunction of an anteroposterior screw adds
      stability. The anterior plane of the osteotomy provides an excellent surface
      contact favoring bone healing. The posterior plane is the same as with a
      "classical" open-wedge osteotomy. The lateral cortical must always remain intact
      (hinge). The technique described here does not require any specific
      instrumentation and is compatible with most of the available osteosynthesis
      implants.

PMID- 18065869
TI  - [Neonatal osteomyelitis of the proximal femur: a case with ten-year follow-up and
      review of the literature].
AB  - Acute hematogenous osteomyelitis most frequently occurs in children, generally
      around 6 to 9 years of age. If it occurs in early infancy, the infection usually
      involves both the bone and the joint, nearly simultaneously. Neonatal
      osteomyelitis is another presentation, with an osteomyelitic focus in the
      metaphysis. We report a case of septic arthritis following osteomyelitis of the
      hip joint in a neonate caused by a virulent pathogenic organism. Despite late
      diagnosis and treatment, outcome was very satisfactory with few sequelae for the
      joint and epiphysis. It should be emphasized that early diagnosis, with prompt
      and adequate treatment is essential to achieve good outcome. We discuss this case
      and present a review of the literature.

PMID- 18065870
TI  - [Thrombosis of the posterior tibial artery complicating closed injury of the
      ankle].
AB  - Closed ankle injury without fracture is a common finding in the emergency room.
      Outcome is generally spontaneously favorable, the injury having no long-term
      clinical impact. Exceptionally, these injuries can be associated with arterial
      damage. We report a case of an apparently benign closed ankle injury which was
      found to be associated with serious arterial damage. Forced dorsal flexion of the
      ankle joint during a traffic accident caused an arterial lesion without any
      apparent damage to the bone and joints. The posterior tibial artery was
      interrupted leading to subacute ischemia of the foot. The diagnosis was
      established 17 days after trauma. Revascularization could not be achieved and leg
      amputation was necessary. This case illustrates the difficulties encountered in
      this type of vascular injury. Most cases in the literature have also involved
      late diagnosis with often serious clinical impact. Clinicians should be aware of
      this rare complication of apparently benign ankle injury because of the risk of
      major loss of function.

PMID- 18065871
TI  - [Can iatrogenic air embolism related to intraoperative use of hydrogen peroxide
      be easily avoided?].
AB  - Air embolism is a rare complication of intraoperative use of hydrogen peroxide.
      We present the case of a young girl who underwent surgery for septic nonunion of
      the femur and developed this complication postoperatively. Outcome was
      fortunately favorable. A review of the surgery and anesthesia literature revealed
      the pathogenic mechanism of this type of accident together with the appropriate
      diagnostic and therapeutic practices. We propose here a series of preventive
      measures based on our experience and data in the literature: inform the
      anesthetist before using hydrogen peroxide, use a cup instead of a syringe for
      administrating hydrogen peroxide and avoid use in deep highly vascularized
      cavities.

PMID- 18065872
TI  - [Dental care and joint prostheses].
AB  - PURPOSE OF THE STUDY: Infectious dental foci and oral dental care constitute one
      of the leading causes of arthroplasty infection after infections involving the
      skin and the urinary tract. There is however no formal evidence confirming the
      relationship between oral or dental care and arthroplasty infection. MATERIAL AND
      METHODS: We reviewed 44 cases of arthroplasty infection secondary to dental
      infections and searched for data in the literature. In our series, no risk factor
      could be identified for 24 cases. The median disease-free interval was five years
      and mean time from the oral-dental procedure to the first signs of prosthesis
      infection was one month. Tooth extraction was the most common oral-dental
      procedure involved (n=19). Most of the infections were caused by a single agent,
      predominantly Streptococci sp. (n=24) and Staphylococci sp. (n=12). DISCUSSION:
      It is well known that dental-related bacteriemia is a spontaneous daily event
      even without dental procedures. It is also probable that spontaneous bacteriemia
      induced by daily activities is much more frequent than dental-care induced
      bacteriemia. The presence of foreign material diminishes local antibacterial
      defense systems increasing the risk of hematogeneous contamination of the joint
      prosthesis after dental care. The oral flora is also modified in immunodepressed
      subjects, particularly carriage of Staphylococcus aureus in the oral cavity which
      is significantly more frequent in patients with rheumatoid arthritis. These
      changes increase the risk of contamination after dental care. For arthroplasty
      infection, the pathogenic power of Staphylococci sp. is certainly greater than
      that of Streptococci sp. even if the inoculum is less abundant. Antibiotic
      prophylaxis during dental care in patients with an arthroplasty remains a
      controversial subject and the most appropriate antibiotic remains to be defined.
      Successive episodes of spontaneous bacteriemia arising from an oral-dental foci
      are probably the main cause of arthroplasty infections, more so than bacteriemia
      triggered by dental care. CONCLUSION: Antibiotic therapy is not indicated for
      routine dental care in the majority of patients but is recommended whenever there
      is a high risk of arthroplasty contamination. In the event of oral-dental
      infection, antibiotic therapy is necessary. The recommendations proposed by the
      ADA and the AAOS were revised in 2003. The most important point is to obtain and
      maintain a good state of oral hygiene. For prevention, awareness of the risk is
      essential, for the patient, the orthopedic surgeon and the primary care physician
      alike. Regular dental visits are necessary.

PMID- 18065873
TI  - [Bibliography on Medline-PubMed. How to seek information by good use of medical
      literature data base].

PMID- 18065874
TI  - [The floating knee: a retrospective analysis of 172 cases].
AB  - A retrospective multicentric observational study of 172 floating knee injuries is
      reviewed. According Fraser's classification 71.5% of the cases are type I and the
      repartition of the type II in the 3 subgroups is as follow: II A 8.2%, II B
      11.6%, et II C 8.7%. At least one of the fractures was open in 69.2% of the
      patients. The average Injury Severity Score (ISS) was 19.5. The polytraumatized
      patients (ISS over 18) represented 37.7% of the cases. The surgical procedure
      started within the 6 first hours in 62% of the injured people. The Intramedullary
      nailing (IM) was the preferred method at the femur site (73%, 126 cases), at the
      tibia IM was performed in 54.4% of cases and external fixation was used in one
      every four patients. The mean operating time was 167 minutes (range: 40'-300')
      and the total time for the whole procedure was 216 minutes (range: 80'-410'). The
      mean follow up is 34.2 months. According the functional score of Karlstrom and
      Olerud, 23 patients were rated as excellent, 38 as good, 35 as fair and 20 as
      bad. The contributing factors influencing bad functional outcome are the age, a
      type II lesion, a femoral fracture located at the distal third, and an open
      fracture. The IM using a single knee incision does not show in this series better
      results but the shortening of the operating time was highly significant.

PMID- 18065876
TI  - [Imaging work-up for recent spinal trauma].
AB  - We focus on the current role of the different imaging techniques used for the
      work-up of recent spinal trauma. We detail the different imaging modalities and
      discuss their respective strengths and weaknesses. We summarize the scope of
      lesions involved, including bony, ligamentous, vascular and nervous injuries. The
      review ends with proposed diagnostic strategies based on these different
      elements.

PMID- 18065877
TI  - [Treatment of thoracolumbar junction burst fractures (Magerl A3) by balloon
      kyphoplasty: anatomic study].
AB  - PURPOSE OF THE STUDY: Balloon kyphoplasty is a not widely used method for the
      treatment of vertebral burst fractures with displacement of the posterior wall.
      The purpose of this study was to measure the posterior height of the vertebral
      body and the posttraumatic canal surface area before and after balloon
      kyphoplasty for the treatment of burst fractures (Magerl A3). MATERIAL AND
      METHODS: This anatomic study was conducted on ten experimental burst fractures of
      the thoracolumar junction prepared on cadaver specimens. The surface area of the
      canal and the height of the posterior wall were measured by computed tomography
      before and after balloon kyphoplasty. These two variables were then compared with
      search for correlation. RESULTS: The posttraumatic canal surface area increased
      significantly after kyphoplasty (p=0.02). Gain in posterior height was not
      significant and there was no correlation between the two variables. Cement
      leakage into the canal was not observed. DISCUSSION: It is known that balloon
      kyphoplasty can re-establish anterior height and correct for the posttraumatic
      kyphosis in patients with compression fractures of osteoporotic vertebrae. The
      present cadaver study shows that when the posterior wall is displaced
      posteriorly, balloon expansion does not exaggerate the wall displacement. On the
      contrary, the posttraumatic canal surface area is increased due to the
      ligamentotaxis effect. CONCLUSION: Balloon kyphoplasty could be an alternative to
      posterior instrumentation for burst fractures without associated neurological
      deficit, even if the posterior wall is damaged. This technique can be used to
      reduce and stabilize the fracture while sparing the adjacent levels and limiting
      the risk inherent with an extensive surgical approach.

PMID- 18065878
TI  - [Botulinum toxin for postoperative care after limb surgery in cerebral palsy
      children].
AB  - PURPOSE OF THE STUDY: Spasticity can be the cause of pain in cerebral palsy (CP)
      children who may suffer increased postoperative pain after orthopedic surgery.
      Moreover, symptoms can be worsened by abnormal movements, cast immobilization or
      anxiety. Spasticity must therefore be treated after surgery in CP children. A
      randomized study has demonstrated that when these children undergo surgical
      tenotomy, preoperative injections of botulinum toxin have a beneficial effect in
      terms of pain relief. The aim of this study was to assess the benefit regarding
      pain and comfort provided by preoperative use of botulinum toxin in total-body CP
      children undergoing bone surgery. MATERIAL AND METHODS: Two successive groups of
      nine total-body CP children were compared in a retrospective study. All patients
      underwent an orthopedic surgery involving a bone or a multilevel procedure. The
      second group was treated before surgery with multisite injections of botulinum
      toxin. The main outcome criteria studied were: efficiency and adverse effects of
      botulinum toxin, duration of hospital stay and pain, length of level III
      analgesic treatment (morphine), sleep quality, and skin lesions under cast
      immobilization. The two groups were similar for mean age (8.7+/-2.04 versus
      10.9+/-4.37 years) and mean body weight (20+/-5.6 versus 26+/-7.7 kg). Mean
      botulinum toxin (Botox/kg) in the second group was 11.6 U (range 9.7-14.8).
      Average time from preoperative botulinum toxin injections to surgery was 27 days
      (range 23-31). RESULTS: There was no significant difference between the two
      groups, except for the botulinum toxin treatment. The Aschworth scale confirmed
      the clinical efficiency of the preoperative injections, with no adverse effects.
      After the surgical procedure, all patients but two had cast immobilization
      (orthopedic traction, in botulinum group). The mean duration was six weeks in
      both groups. There was no significant difference in duration of the hospital
      stay: 7.33+/-1.5 versus 7.88+/-1.7 days and duration of level III analgesic
      treatment (4.33+/-1.9 versus 4.16+/-2.5 days). The duration of pain symptoms
      decreased significantly from 6.87+/-2.9 to 2.22+/-1.7 days and sleep quality
      improved from 7/9 to 1/9 patients with disturbed sleep. Four under-cast skin
      lesions were noted in the first group but none in the bolulinum group.
      DISCUSSION: We cannot confirm that botulinum toxin before bone surgery induces
      lesser consumption of analgesic drugs. Our results do however support the
      hypothesis that treatment of spasticity using preoperative injections of
      botulinum toxin decreases the duration of postoperative pain and improves the
      children's comfort. Moreover, postoperative under-cast skin lesions can be
      prevented. This work suggests that improved patient comfort and pain relief could
      be achieved by using multisite botulinum toxin injections before orthopedic
      surgery in spastic total-body CP children.

PMID- 18065879
TI  - [Treatment of mallet finger with dorsal nail glued splint: retrospective analysis
      of 270 cases].
AB  - PURPOSE OF THE STUDY: Management of mallet finger is both difficult and
      controversial. Sequelae are not uncommon, particularly after surgical treatment.
      Many authors advocate orthopedic treatment which is less invasive but requires
      greater patient participation to implement. Despite the large number of
      orthopedic methods proposed, none has proven superiority. We report here our
      experience with a dorsal adhesive splint which preserves digital pulp function
      and improves observance. MATERIAL AND METHODS: This retrospective analysis
      included 270 mallet fingers presenting 153 tendon injuries and 117 bony injuries
      in 265 patients aged 42 years on average and treated from 2003 to 2005. Most of
      the tendon injuries involved the medius (38.7%) and most of the bony injuries
      involved the ring finger (35.4%). A splint was fashioned for the two distal
      phalanges and glued to the nail plate filed for this purpose. The splint was
      fashioned out of an L-shaped plastic sheet of thermo-malleable plastic dipped in
      hot water (60 degrees C). The L was molded to the dorsal aspect of the phalanges
      and rolled like a ring around the second phalanx, then glued to the nail. The
      splint was worn for eight weeks by patients with a tendon injury and six weeks
      for those with a bony injury. The splint was then worn at night for two weeks.
      Three criteria were used to analyze outcome: residual extension deficit, joint
      involvement, complications. RESULTS: Mean follow-up was 18 months. Mean time from
      trauma to definitive installation of the splint was six days. The complication
      rate for this orthopedic method was 14.3%, complications being observed in 6% of
      patients. All complications were transient except for one case of swan neck
      deformity and one case of painful osteoarthritis. Thirty splints (11%) became
      unglued but were all reinstalled using the same protocol. Thirty fingers (14%)
      presented residual deficit of active extension measuring less than 20 degrees.
      The quality of the result depended on the type of injury: tendon injuries led to
      extension deficit in more fingers (20% versus 7.5%) but for a lesser degree (16.5
      degrees versus 19.1 degrees) than bony injuries. DISCUSSION: We observed a lower
      rate of complications with this technique than usually reported in the
      literature. Transient ungueal dystrophy only involved 2.5% of the fingers in our
      series. Swan neck was observed in only 8.3% of the fingers, all with tendon
      injuries, and resolved in all. There was only one case of symptomatic distal
      interphalangeal joint degeneration among the 117 fingers with bony injuries.
      There were no cases of skin necrosis. The results of this retrospective study,
      with mean 2.38 degrees extension deficit, are better than reported in other
      series in the literature. These results suggest that surgical indications for
      mallet finger should be revisited, irrespective of the type of injury, excepting
      when subluxation persists despite installation of the splint. CONCLUSION: In
      conclusion, our series demonstrates that the adhesive dorsal splint is an
      effective treatment for all types of mallet finger, reducing the number of
      indications for surgery. Compared with other techniques, the advantages are: free
      digital pulp, better patient observance, lesser extension deficit.

PMID- 18065880
TI  - [Permanent, habitual dislocation and recurrent dislocation of the patella in
      children: surgical management by patellar ligamentous transfer in 50 knees].
AB  - PURPOSE OF THE STUDY: Appropriate treatment of patellar dislocation in children
      and adolescents remains a subject of debate. Ligamentous transfer or "soft rod"
      is a technique for realigning the extensor mechanism that can be adapted to
      children. We analyzed results obtained in our patients. MATERIAL AND METHODS:
      Between 1979 and 2000, 35 children (50 knees) underwent realignment which was
      combined in all cases with lateral retinacular release and medial reefing using
      the Insall procedure. Complementary procedures were needed in certain cases
      (quadriceps lengthening, femoral sulcus plasty, quadriceps release). Mean age at
      surgery was 11 years, range 5-15 years. All patients were reviewed at skeletal
      maturity with a mean follow-up of 7.5 years. The last review included a
      functional assessment using the IKDC form and standard x-rays (anteroposterior
      and lateral standing view and tangential view at 30 degrees flexion). A computed
      tomography scan and/or magnetic resonance imaging series were done preoperatively
      and at last follow-up. DISCUSSION: We distinguished two groups of patients, those
      with major (permanent or habitual) dislocation of the patella and those with
      recurrent dislocation. Functional outcome was good in 76% and 86% of knees
      respectively. There were eight cases of recurrent dislocation: five knees
      underwent revision surgery with good outcome. The femoral sulcus angle was
      improved in both groups, but especially in the congenital dislocation group.
      There was on case of reversed tibial slope (-2 degrees) ant to slopes at 0
      degrees. Functional outcome was equivalent to results from earlier series
      (Grammont, Bensahel, Langeskiold), but comparison was hampered due to the
      heterogeneous nature of the different series. Femoral sulcus remodeling can
      enable good patellar stability if the surgery is performed early enough (before
      age 10 years). In teenagers with major instability, femoral sulcus plasty must be
      associated with the realignment procedure. We noted a small amplitude reduction
      of the tibial slope in eleven knees. The procedure appears to have an
      "epiphysiodesis effect" but with no functional consequence. CONCLUSION:
      Ligamentous transfer combined with different procedures is a method of choice for
      stabilizing the extensor system, enabling a normal femoral sulcus angle if the
      child is operated early. Remodeling of the tibial tuberosity could be related to
      a transient vascular disorder.

PMID- 18065881
TI  - [Treatment of deep cartilage defects in the knee with autologous chondrocyte
      transplantation: a review of 28 cases].
AB  - PURPOSE OF THE STUDY: The knee has little capacity for spontaneous regeneration
      of deep cartilage defects. In 1999, the French Society of Arthroscopy initiated a
      multicentric clinical trial on autologous chondrocyte transplantation using the
      technique described by Brittberg and Peterson. The protocol of this prospective
      study was validated by the ethics committee and all patients provided the
      informed consent for participation. MATERIAL AND METHODS: Patients underwent
      surgery in seven hospitals: 28 patients (7 female, 21 male, mean age 28 years,
      age range 18-45 years). The underlying condition was: osteochondritis (n=14),
      isolated posttraumatic chondropathy (n=8), chondropathy plus ACL tear (n=6). All
      patients presented deep condylar cartilage defects (ICRS grades 3 and 4). Mean
      surface area involved after debridement was 490 mm2 (range 150-1050 mm2).
      Patients were reviewed two years at least after transplantation for functional
      assessment and an MRI performed 2 to 3 years after transplantation. Control
      arthroscopy was also performed in 13 patients with biopsy for histology and
      immunohistochemistry for 10. RESULTS: Twenty-six patients were reviewed with more
      than two years follow-up (mean 2 years 9 months). There were no general
      complications; three patients presented a partial avulsion of the autograft
      treated arthroscopically and one arthrolysis was performed at six months.
      Function was improved in all patients but four, but pain persisted in one
      patient. The mean ICRS score improved from 41 points (19-55 points) to 74 points
      (54-86 points), for an 80% gain. Follow-up MRI was available for 16 knees: the
      graft was hypertrophied in 11, at level in 3 and insufficient in 2; marginal
      integration was good in 10 knees and fair in 6. Items of marginal and subchondral
      integration had a very high positive predictive value for good clinical outcome.
      The arthroscopic score was nearly normal (range 8-11) in 8 knees and abnormal
      (range 4-7) in 5. The Knutsen histological groups according to richness of
      hyaline cartilage were: group 1 (>60%) (n=1); group 2 (>40%) (n=3), group 3
      (<40%) n(=4) and group 4 (bone or fibrous tissue) (n=1). The function scores
      (r=0.80) and the MRI scores (r=0.76) were correlated with the arthroscopy scores.
      There was no correlation between the histological findings but the sample size
      was too small for meaningful analysis. DISCUSSION: The clinical results
      demonstrate an improvement in more than 80% of knees, findings similar to earlier
      reports. The arthroscopic and histological results were equivalent to those
      reported by Knutsen, but less satisfactory than those reported by Bentley or
      Peterson. Cell injections under a periosteal patch constitute the first
      generation of autologous chondrocyte grafts. Resorbable matrices loaded with
      chondrocytes before implantation are under development and have provided
      promising early results.

PMID- 18065882
TI  - [Complications of first ray osteotomies: a consecutive series of 475 feet with
      first metatarsal Scarf osteotomy and first phalanx osteotomy].
AB  - PURPOSE OF THE STUDY: Available studies on Scarf osteotomies of the first
      metatarsal (M1) and first phalange (P1) shortening and varus displacement have
      reported good results, but have have not focused on complications. We reviewed a
      consecutive series of 475 feet operated on over a five year period. Our goal was
      to determine the incidence of complications and to compare our data with reports
      in the literature. We wanted to know if association with Weil osteotomy on the
      lateral metatarsals affects the rate of complications. MATERIAL AND METHODS: We
      used the following inclusion criteria: hallux valgus>35 degrees, adult subject,
      with or without impact on the lateral ray, no prior foot surgery, no systemic
      disease, no other co-morbid condition. We distinguished two groups: group 1 with
      isolated first ray disease, and group 2 with hallux valgus and lateral
      metatarsalgia requiring surgery. RESULTS: We determined the incidence of each
      complication. Metatarso-phalangeal joint (MTP1) stiffness was the most frequent
      complication: incidence declined with postoperative time: 41.7% at day 35, 5.7%
      at day 120. The joint was very stiff with defective pulp weight-bearing in 1.3%
      of the feet at 12 months. Late wound healing was observed in 5.7% of feet and
      secondary osteotomy displacement in 1%. Incidence of other complications,
      including operative site infection, was less than 1%. General complications were:
      reflex dystrophy (1.3%) and deep vein thrombosis (0.6%). Excepting a longer
      period of postoperative stiffness, we were unable to identify any change in the
      rate of postoperative complications in feet with an associated Weil osteotomy of
      the first ray. DISCUSSION: Our findings confirm that Scarf M1 osteotomies with
      varus shortening of P1 generates fewer complications than the techniques used
      earlier. Certain complications have disappeared: nonunion after M1 and P1
      osteotomy, great toe claw, symptomatic iatrogenic hallux valgus. Complications
      with a very low incidence in all series are: operative site infection,
      osteonecrosis of the M1 head, fracture of M1 at weight bearing. Notching of the
      two osteotomy pieces with elevation of the metatarsal head and transfer
      metatarsalgia has been reported by authors using short diaphyseal osteotomies. A
      stiff MTP1 remains the most frequent complication. Overtly stiff joints (30% loss
      of range of motion) were observed in 4.6% of our patients at 12 months; 1.3% had
      major stiffness (20 degrees extension, 0 degrees plantar flexion). This stiffness
      has been reported by others using the same technique but the risk factors have
      not been identified. CONCLUSION: This prospective work enabled us to establish
      the rate of secondary complications of first ray surgery for M1 Scarf osteo-tomy
      and P1 osteotomy. Complications are rare, a further argument favoring use of
      these osteotomies. This statistical study enables us discuss the risk of
      complications at the preoperative interview, keeping in mind the specific
      elements inherent in each particular situation.

PMID- 18065883
TI  - [Anatomic danger of percutaneous section of the inter-metatarsal ligament for the
      treatment of Morton's neuroma].
AB  - Certain authors have proposed percutaneous neurolysis of Morton's neuroma. We
      conducted a human anatomy study to assess the reliability and the iatrogenic
      effect of percutaneous section of the ligament. Percutaneous section of the inter
      metatarsal ligament was performed on 16 fresh cadaver specimens via a dorsal
      approach. The plantar dissection demonstrated that the section was not complete,
      without associated lesion, in only six cases. Analyzing these failures, we
      determined the necessary procedure for correct section.

PMID- 18065884
TI  - [Floating first metacarpal with recurrent trapeziometacarpal dislocation in a
      subject with hyperlaxity].
AB  - A case of trapezometacarpal dislocation associated with metacarpophalangeal
      dislocation (floating first metacarpal) is described. The trapezometacarpal
      dislocation re-occurred twice despite well conducted orthopedic treatment.
      Ligamentoplasty of the carpal radial flexor tendon using the Eaton and Littler
      method then provided an excellent result. Failure of orthopedic treatment was
      probably related to the congenital hyperlaxity presented by this patient.
      Considering this hypothesis, the presence of hyperlaxity would affect management
      practices used for trapezometacarpal dislocation. In the presence of hyperlaxity,
      it would be preferable to propose first-intention surgery with suture and pinning
      or ligamentoplasty. Conversely, for patients without hyperlaxity, orthopedic
      treatment remains the first-intention treatment of choice.

PMID- 18065885
TI  - [Traumatic lumbosacral fracture dislocation: a case report and review of the
      literature].
AB  - Lumbosacral dislocation is uncommon. We report a case of traumatic lumbosacral
      dislocation which occurred in a 33-year-old pedestrian traffic accident victim.
      The posterior impact produced lumbar injury with diffuse pain exacerbated at the
      lumbosacral junction. Ecchymotic diffusion involving the entire lumbar region
      fluctuated due to the presence of a subcutaneous hematoma. The neurological
      examination revealed incomplete L5 paraplegia. Standard x-rays revealed L5-S1
      spondylolisthesis and fracture of the L5 spinous process as well as fractures of
      the L3, L4, and L5 transverse processes. Computed tomography disclosed
      biarticular L5-S1 fracture dislocation and a voluminous herniation of the L5-S1
      disc. Emergency surgery was performed and revealed subaponeurotic detachment from
      T4 to S1 and bald iliac pyramids. After L5 laminectomy and extraction of the
      voluminous herniation of the L5-S1 disc, a short L5-S1 posteriolateral fusion was
      achieved using pedicular screws and two rods on either side as well as a
      posterolateral iliac autograft. The clinical course was satisfactory with nearly
      complete neurological recovery (persistent levator ani paresis). This clinical
      case and a review of the literature illustrate the pathogenic, clinical,
      radiological and therapeutic aspects of lumbosacral fracture dislocation.

PMID- 18065886
TI  - [Osteoid osteoma of the inferior articular process of L5 associated with a
      bilateral spondylosis: a case report].
AB  - We report the case of an 8-year-old boy who presented an osteoid osteoma of L5
      associated with bilateral spondylolysis involving the same vertebra. Diagnostic
      bone scintigraphy is highly contributive in children presenting back pain. For
      us, it is the first intention exploration in patients with isthmic lysis seen on
      the plain x-ray. Symptomatic spondylolysis is the most frequent cause of back
      pain in children and is much more frequent than vertebral osteoid osteoma. The
      presence of isthmic lysis associated with focal uptake on the bone scintigraphy
      is highly suggestive of symptomatic spondylolysis. In this context, magnetic
      resonance imaging should be performed for both diagnostic purposes and prognostic
      assessment. The degree of bone and soft tissue edema in the present case was
      unusual for symptomatic spondylolysis. Complementary computed tomography finally
      established the diagnosis of osteoid osteoma of the posterior vertebral arch. To
      our knowledge, the association of osteoid osteoma with bilateral spondylolysis on
      the same vertebra has not been described elsewhere. In children, the diagnosis of
      symptomatic spondylolysis can only be established after ruling out other causes
      of back pain. The diagnosis of osteoid osteoma must be kept in mind.

PMID- 18065887
TI  - [Tarsal osteoarthritis: a rare localisation of tuberculosis].
AB  - We report the case of a 39-year-old woman with an uneventful medical history who
      presented an inflammatory left foot with no notion of trauma or fever. The plain
      x-ray and magnetic resonance imaging demonstrated talonavicular and subtalar
      osteoarthritis. A surgical biopsy with excision of inflammatory and necrotic
      tissue and removal of a fistular tract was performed. Histology revealed the
      presence of granulomas with caseous central necrosis suggesting tuberculosis of
      the bone. The diagnosis was confirmed when bacteriology samples grew
      Mycobacterium tuberculosis. Antituberculosis drugs were administered for twelve
      months. At 24 months, the patient presents a painful stiff rear foot after the
      development of secondary talonavicular degeneration. This case illustrates a
      particular clinical presentation of tuberculosis. This diagnosis should be
      considered in the presence of atypical bony lesions with a chronic course. Early
      diagnosis enables proper therapeutic management. Useful diagnostic imaging
      techniques include plain x-rays, computed tomography, and magnetic resonance
      imaging. Certain diagnosis is based on bacteriological and histological
      examinations.

PMID- 18065888
TI  - [Changing surgical treatment for congenital hip dislocation in children and
      adolescents in a referral hospital in Lebanon].

PMID- 18065889
TI  - [Risk management and accreditation of orthopedic surgeons and traumatologists].

PMID- 18065891
TI  - [Bile duct injury during laparoscopic cholecystectomy].

PMID- 18065892
TI  - [Management of hilar cholangiocarcinoma].
AB  - Hilar cholangiocarcinoma is a rare disease departing from the biliary
      convergence. It is primarily revealed by the onset of retention jaundice. Only
      20%-30% of patients can undergo resection at diagnosis. The only chance for
      survival for these patients is R0 resection, which requires hepatectomy
      associated with resection of the common bile duct and pedicle lymph node removal,
      whatever the classification of the cholangiocarcinoma. No adjuvant treatment has
      been shown to be effective to date. Palliative treatment is most often based on
      implanting a biliary stent. Dynamic phototherapy may be beneficial in these
      situations. Improvements in survival for selected N0 hilar cholangiocarcinoma may
      be obtained with neoadjuvant treatment with radiochemotherapy followed by liver
      transplantation.

PMID- 18065893
TI  - [Neoadjuvant treatments in digestive cancer].
AB  - Neoadjuvant chemotherapy or chemoradiotherapy is an important concept in the
      treatment of colorectal liver metastasis, gastric cancer, and esophageal or
      rectal tumors. This treatment strategy improves disease-free survival and
      sometimes overall survival. It allows surgical resection of lesions that where
      not resectable at diagnosis. The new standards of neoadjuvant treatments in
      gastrointestinal oncology are described in this article.

PMID- 18065894
TI  - [What can be expected from digestive tract MRI?].
AB  - With recent technological progress, MRI can now reliably explore the digestive
      tract. Gastrointestinal MRI can map small intestine involvement in Crohn disease,
      with no irradiation in young patients. In addition, MRI provides supporting
      arguments for inflammatory or fibrous involvement of the intestine. MRI of
      anoperineal fistulae is useful in the preoperative stage to plan surgical
      treatment so as to reduce the recurrence rate of complex fistulae or recurring
      fistulae. In rectal cancer, MRI is the best examination to evaluate perirectal
      fascia for choosing neoadjuvant treatment.

PMID- 18065895
TI  - [Treatment of biliary injuries after laparoscopic cholecystectomy: retrospective
      study of 27 patients].
AB  - Biliary injuries after laparoscopic cholecystectomy are rare but serious. Their
      mortality rate can reach 9%. AIM OF THE STUDY: Describe the management of biliary
      injuries after laparoscopic cholecystectomy in our center. PATIENTS: Between
      January 1995 and June 2005, 27 patients (13 women, 14 men) were treated. The mean
      age was 53 years old (range, 18-92 years). The biliary injuries were common bile
      duct sections (n=16, 60%), common bile duct stenoses (n=5, 18.5%), biliary
      fistulas from the cystic duct (n=4, 15%), and biliary fistulas from an aberrant
      biliary duct (n=2, 7.5%). RESULTS: Acute cholecystis was present in 40% of cases
      (n=11). An intraoperative cholangiography was done in 12 patients (44%). The
      mortality rate was 0%. Of the common bile duct sections, 43% were diagnosed
      during the cholecystectomy (n=7) or after the cholecystectomy within a mean of
      11.2 days (n=9). Common bile duct injuries were treated in 16 cases with
      hepatojejunostomy and in five cases with an external biliary drain. Fistulas from
      the cystic duct were diagnosed within a mean 14.8 days. A fistula from an
      aberrant biliary duct was diagnosed during the cholecystectomy (n=1) or in the
      second postoperative day (n=1). Fistulas were treated with a clip on the cystic
      duct (n=2), an external biliary drain (n=1), a biliary endoprosthesis (n=1), and
      the biliary aberrant duct suture (n=2). CONCLUSION: Common bile duct injuries are
      a serious complication because their treatment is a hepaticojejunostomy in 75% of
      cases.

PMID- 18065896
TI  - [Iatrogenic biliary injuries during cholecystectomy].
AB  - AIM OF THE STUDY: To analyze our experience with biliary injuries during
      cholecystectomy in order to determine associated risk factors, morbidity, and
      results after reconstruction. PATIENTS AND METHODS: Review of the series of
      patients referred to our department for biliary injury during cholecystectomy
      over a 9-year period. Items regarding the type of lesion, risk factors,
      management, morbidity, and late results were recorded. RESULTS: Fifteen patients
      were referred to our department for bile duct injury during cholecystectomy
      between 1997 and 2005 (14 by laparoscopy and four by laparotomy; nine women and
      nine men). The main surgical indication was biliary colic (n=8). Three patients
      were operated on in an emergency setting (for acute cholecystitis). In nine
      patients the gallbladder wall was inflammatory. Intraoperative cholangiography
      was performed in nine patients, but revealed just one injury. Lateral injury to
      the bile duct was the most frequent type of lesion. In nine patients, the injury
      was detected intraoperatively and a biliary drainage was left in place; five of
      them had a synchronic repair and three required later reconstruction. Nine
      patients had a delayed identification of biliary injury; six of them required a
      biliodigestive anastomosis. Two patients died, three had several episodes of
      acute cholangitis after reconstruction and two presented incisional hernia.
      CONCLUSION: An inflammatory environment is the main risk factor for biliary
      injury during cholecystectomy. Bile duct injury is more frequent with
      laparoscopic cholecystectomy but can also occur with an open approach.
      Intraoperative cholangiography does not prevent biliary injuries nor detect them
      accurately. Biliary drainage can reduce morbidity for intraoperatively detected
      injuries and may be a sensitive approach for the surgeon with no hepatobiliary
      experience. Morbidity is increased in patients with delayed identification of the
      injury.

PMID- 18065897
TI  - [Cancer and spirituality: does knowledge of disease affect the degree of faith?].
AB  - OBJECTIVE: To measure the influence of knowledge of one's cancer on the degree of
      religious faith in patients Method: Questioning of 117 patients with cancer who
      were admitted to the oncology department of the Hotel Dieu de France Hospital
      during the period from 24 November 2005 to 1 December 2005, and filling out of an
      Arabic version of the SCSORF questionnaire: the higher the score on this
      questionnaire, the more it indicates a high level of religious faith. RESULTS: We
      found a higher score in patients who knew about their disease than in those who
      did not (p<0.001), a higher score in women than in men (p<0.05), a higher score
      in Muslims than in Christians (p<0.01), but Christians had a higher score on the
      question concerning comfort in religious faith (p<0.001), a higher score in
      patients with relapse of their disease than those with no relapse (p<0.01), and a
      higher score in patients who were not taking benzodiazepines than in those who
      were taking them (p<0.05). We also found a positive correlation between education
      level and knowledge of the disease (p<0.05), a positive correlation between the
      time lapsed since diagnosis and the frequency of prayer (p<0.05), and a negative
      correlation between education and the preference for being in a group of people
      of the same faith (p<0.05). CONCLUSION: This study is the first to demonstrate
      that knowing one's cancer diagnosis is a factor that increases the degree of
      religious faith, independently of the everyday stress experienced by the patient.
      This underscores the importance of the patient's faith in better controlling the
      symptoms of the disease and the side effects of the treatments, with a reduction
      in the use of benzodiazepines.

PMID- 18065898
TI  - [The place of laparoscopy in the management of the patients with penetrating
      abdominal trauma].
AB  - INTRODUCTION: In patients with an abdominal knife wound, the main problem is to
      determine whether the abdominal trauma is penetrating. The aim of this work is to
      study the safety of the laparoscopic approach in the management of abdominal
      knife trauma. MATERIALS: A laparoscopy was performing in sixty patients. Patients
      were dispatched in four categories according to the laparoscopic findings. A
      laparotomy was performed after laparoscopy in case of peritoneal tear. RESULTS:
      Unnecessary laparotomy was avoided in 58% of the patients. The follow-up was
      favourable with nil mortality and a low morbidity (3%). CONCLUSION: Laparoscopic
      management of abdominal wound knife trauma is a reliable approach to identify a
      peritoneum tear. This specific situation requires a laparotomy to look for an
      intra abdominal tear.

PMID- 18065899
TI  - [Comment on the article by Leonard et al. on the place of laparoscopy in managing
      stab wounds].

PMID- 18065900
TI  - [Left hepatectomy: open technique].

PMID- 18065901
TI  - [Left hepatectomy: laparoscopic technique].

PMID- 18065902
TI  - [Left lobectomy with extraparenchymal control of portal pedicles].

PMID- 18065903
TI  - [Emphysematous gastritis].

PMID- 18065904
TI  - [Angiocholitis after cephalic duodenopancreatectomy].

PMID- 18065905
TI  - [Appendectomy for appendicitis by colonoscopy after a cecal invagination of the
      appendix during childhood].
AB  - Appendiceal intussusception (the inside-out appendix) was often practiced in
      pediatric surgery when the appendectomy was performed during laparotomy.
      Complications are exceptional. We report the first case of appendiceal
      intussusception in an adult appendectomized by this procedure during childhood,
      reviewing the radiological aspect, pathogenesis, and treatment. This delayed
      complication of appendiceal intussusception should be known to the surgeon.
      Treatment during colonoscopy is possible. This inflammation of the vaginated
      appendix can be prevented by coagulating the appendicular vessels to the serous
      membrane before turning it inside-out.

PMID- 18065906
TI  - [Solitary ulcer of the colonic hepatic flexure].
AB  - The nonspecific colon ulcer is a not a well-known disorder. A case of ulcer of
      the colic hepatic flexure is described. It was a case of pseudotumor and the
      pathological examination confirmed the diagnosis. The precise diagnosis of colon
      ulcer is useful for conservative treatment with coloscopic surveillance and to
      prevent a hemorrhagic complication or peritonitis after perforation. Contrary to
      diverticulitis, this pathology is most dominant on the right colon and
      particularly on the cecum. This explains the frequency of pseudoappendicular
      syndromes.

PMID- 18065907
TI  - [Writing the surgical report].

PMID- 18065908
TI  - [Expert agreement on the minimal descriptive surgical report for peritoneal
      cancer].

PMID- 18065909
TI  - [Negative pressure wound therapy: pleading for an agreement].

PMID- 18065910
TI  - [Arteria lusoria].

PMID- 18065912
TI  - [Indications for inguinal hernia repair].
AB  - The surgical results of inguinal hernia repair depend on the operative
      indications. When surgery is being discussed, four factors should be taken into
      account: patient age and sex, the type of hernia (location, age, side,
      recurrence), and the patient characteristics that favor hernia onset or increase
      the surgical risk. In females, hernias are for the most part femoral, and
      inguinal hernias are rarely isolated. Femoral hernias and hernias that have
      recently appeared are at a high risk for strangulation. The complications of
      recurring hernias are always serious. These hernias should be treated no matter
      how old the patient is, with the risk of strangulation increasing above the age
      of 65. A repair procedure can be done under local anesthesia with no increase in
      the postoperative complication rate, even in older patients and patients who are
      at high risk for surgery. On the other hand, interventions done in an emergency
      situation induce excessive morbidity and mortality, which persist during the year
      following the surgery. Hernial strangulation multiplies postoperative morbidity
      by 2.67 and mortality by 10. In cases of asymptomatic bilateral hernia with no
      risk of complication, the indication should be weighted by age and any associated
      comorbidities. Finally, with an old hernia, the surgical risk should be compared
      to the risk of strangulation.

PMID- 18065911
TI  - [Classic and endoscopic surgical anatomy of the groin].
AB  - Knowledge of the groin's anatomy is indispensable to understanding the
      pathological anatomy of hernias and their surgical treatment. Although classical
      anatomy provides an understanding of the techniques of open surgery, learning
      celioscopic techniques requires a new mental representation and specific
      training. The objective of this focus was to describe the anatomic approaches to
      inguinal hernias and compare them to those described during the celioscopic
      approach.

PMID- 18065913
TI  - [Femoral hernias: repair techniques].
AB  - Femoral hernias are diagnosed in more than 50% of cases during strangulation.
      This is predominantly a female disorder. Given the configuration of the femoral
      ring itself, these hernias are difficult to diagnose and carry a high risk of
      strangulation (risk multiplied by 10) and visceral pain. Postoperative morbidity
      and mortality after intervention in an emergency situation surpasses 10%. A
      diagnosed femoral hernia should therefore always be operated. This type of hernia
      is rarely associated with an inguinal hernia and the femoral approach is
      recommended. If the superficial ring is less than 15 mm in diameter, the Lytle
      procedure is recommended; in all other cases, one must avoid generating excessive
      tension on the tissues and thus increasing the risk of recurrence. The modified
      Lichtenstein, Plug(R), or transabdominal preperitoneal (TAPP) techniques are best
      in this situation. In males, femoral hernias are rare and in more than half the
      cases are associated with an inguinal hernia. The abdominal wall-strengthening
      technique should be used to treat all the hernial rings so that an inguinal
      hernia does not occur postoperatively. Here tensionless techniques are also
      preferred, a McVay repair respecting the long incision on the sheath of the
      abdominal rectus, the modified Lichtenstein procedure, the Rives technique, or
      video-assisted techniques. During hernial strangulation, even if using mesh
      repair does not seem to increase the risk of sepsis, herniorrhaphy repair should
      be preferred.

PMID- 18065914
TI  - [Anterolateral hernias of the abdomen].
AB  - Anterolateral hernias of the abdomen group together umbilical, epigastric, and
      spigelian hernias and diastasis of the abdominal rectus. In spigelian hernias,
      90% are located in the subumbilical region at the Monro line. They are
      asymptomatic in 90% of cases. The risk of strangulation is 10%-25% and requires
      surgical treatment. A herniorrhaphy is sufficient if the ring is less than 2 cm
      in diameter. Beyond 2 cm, open or celioscopic mesh repair is necessary. The risk
      of recurrence is less than 2%. Umbilical hernias result from progressive
      enlargement of the umbilical ring. The risk of strangulation is higher than 10%.
      The morbidity and mortality rate reaches 15% in large strangulated hernias. All
      umbilical hernias should therefore be treated surgically. If their diameter is
      under 2 cm, a simple herniorrhaphy can be done; otherwise mesh repair is
      required. In the cirrhosis patient, hernia treatment is part of the ascites
      treatment. The indication for surgery depends on liver function. Epigastric
      hernias are most often symptomatic: 80% have a ring smaller than 25 mm and 20%
      are multifocal. The risk of strangulation is low. If the ring is less than 20 mm,
      these hernias can be treated by herniorrhaphy. Recurrence is frequent - more than
      10% - and always difficult to treat. Diastasis of the recti does not lead to
      complication, and treatment is not necessary. Cosmetic surgery can be used to
      manage diastasis.

PMID- 18065915
TI  - [Diaphragmatic hernias, excluding hiatal hernias with gastroesophageal reflux].
AB  - Large, mixed hiatal hernias are usually found between the ages of 60 and 70
      years, with a female predominance (60%). The natural history is progression
      toward the appearance of symptoms, although 30%-40% of patients are initially
      asymptomatic. Symptoms develop quietly. The indication for surgical treatment of
      hiatal hernias amounts to considering the risks of leaving it in place. The
      literature reports a morbidity and mortality rate related to the complications of
      these hernias, leading to emergency interventions, which have an incidence of
      1.16%.with a 27% mortality rate. Morbidity appears different depending on the
      approach used: laparoscopy or laparotomy (4.3% versus 16%). The debate continues
      on whether to monitor or treat these hernias, with a lack of consensus on the
      indications and the technique. However, the laparoscopic approach shows a gain in
      the length of the hospital stay, an easier approach to the hiatus in the
      diaphragm, and a lower morbidity and mortality rate. Fundoplication is advised,
      as well as placing prosthetic mesh if the orifice is larger than 8 cm. There is
      no indication for lengthening the esophagus (Collis-Nissen fundoplication).

PMID- 18065916
TI  - [Internal abdominal hernias].
AB  - Internal hernias are complete or partial protrusions of one or several viscera or
      tissues through an intraperitoneal orifice remaining in the abdominal cavity.
      Whatever the type or anatomical location may be, the seeming banality and lack of
      specific symptoms contrasts with the seriousness of complications such as
      strangulation followed by ischemia or intestinal necrosis. Delay in diagnosis can
      be shortened if these complications are kept in mind at diagnosis and if the
      imaging studies are illustrative. At the least doubt, surgery will correct the
      diagnosis and allow adapted treatment.

PMID- 18065917
TI  - [Inguinal hernia. What techniques are available for the surgeon? Theoretical and
      practical advantages and disadvantages].
AB  - There are many hernia repair techniques. Among the most popular, the Shouldice
      Hospital method was the most widely used in the 1980s. Since then, methods
      employing prosthetic mesh have taken over, mainly because they are tension-free
      and therefore seem to lead to less recurrence and cause less postoperative pain.
      There are several ways of placing the prosthesis, which differ according to the
      approach used and the superficial or deep situation of the prosthesis. The
      Lichtenstein technique consists of placing and fixing the prosthesis on the
      posterior wall of the inguinal canal through an inguinal incision: it is
      currently the most widely used procedure because of its simplicity. The concept
      of placing the prosthesis in the subperitoneal space was developed by the French
      school (Rives, Stoppa). Initially the operation was performed through an inguinal
      (Rives) or midline (Stoppa) incision. These techniques are no longer adapted to
      the minimally invasive concept of surgery that prevails today and therefore are
      less used. The laparoscopic approach places the prosthesis through the trocars
      instead of through a large incision. The transabdominal approach opens the
      preperitoneal space through the abdominal cavity, breaching the peritoneum. The
      extraperitoneal approach consists of direct penetration of the preperitoneal
      space without violating the peritoneum, as in the Stoppa technique. This is
      undoubtedly the most elegant laparoscopic technique, but more difficult to
      perform. Other, simpler methods can also reinforce the posterior wall with a
      preperitoneal prosthesis. The Polysoft prosthesis, placed through an inguinal
      incision and inguinal ring, is a modern substitute for the Rives technique, but
      can be performed under local or locoregional anesthesia. Other types of
      prostheses, consisting of two, both superficial and deep, components are
      available: the Prolene Hernia System, for instance, is composed of two circular
      plates, linked together by a central stalk; there are also several types of
      plugs. As for anesthesia, there are several evidence-based arguments that
      indicate that local anesthesia is best.

PMID- 18065918
TI  - [Should all asymptomatic inguinal hernias be surgically corrected?].
AB  - Femoral hernias present a high risk of strangulation and should be treated with
      surgery as soon as the diagnosis is made. Inguinal hernias present a low risk of
      strangulation, an argument for surgery only in patients who do not have rapid
      access to a surgical center. In the other cases, delaying hernia treatment seems
      to have few advantages in that patients are operated in the end and that during
      the waiting period, their health is generally poorer than operated patients'
      health. Other than patients presenting serious co-morbidities or with a short
      life expectancy, asymptomatic inguinal hernias should be repaired in all patients
      who so desire. This decision is made in agreement with the patient after he or
      she has been clearly informed on the risks, the sequelae, and the results of
      surgery. With bilateral hernias, one of which is symptomatic, it seems preferable
      to treat both hernias in the same anesthetic time frame. In case of a hernia
      occurring simultaneously with another intervention, it should be treated only
      after the patient has given consent.

PMID- 18065919
TI  - [Causes of complications and failures of hernia repair: how to avoid them].
AB  - Prevention of complications of inguinal hernia repair is first of all based on
      precisely dissecting the hernial sac and respecting the components of the
      spermatic cord and the blood vessels of the region. Resecting the sac is not
      necessary if it can easily be reintegrated into the abdominal cavity. Muscle
      reinforcement with synthetic mesh is the method that provides the most reliable
      repair. Systematic antibiotic therapy with prosthetic repair does not seem
      necessary if there is no risk factor for infection. During laparoscopy, the mesh
      must be a minimum of 10 x 15 cm; it is preferable not to attach it to prevent any
      nerve lesion. If necessary, fixation should be minimal and avoid nerve passage
      zones. During recurrence surgery, using an approach different from the preceding
      procedure is preferred so as to prevent dissection within the scar tissue.

PMID- 18065920
TI  - [How should acute complications of inguinal hernias in adults be treated?].
AB  - The frequency of hernia strangulation seems relatively low in developed countries
      and seems to be declining in parallel with the development of elective hernia
      surgery. The seriousness of the disorder to a large extent justifies the
      indication for surgery in cases of noncomplicated hernia. When strangulation
      occurs, rapid diagnosis and treatment, before necrosis sets in, is the first
      imperative to guarantee that progression is uneventful.

PMID- 18065921
TI  - [Cost of laparoscopic and open incisional hernia repair].
AB  - The economic impact of new technologies must be analyzed and known by surgeons.
      In laparoscopic incisional hernia repair, the cost of surgery is higher than open
      repair because of the longer duration of surgery and the cost or materials. The
      cost of the hospital stay is lower because the stay is shorter and the
      postoperative complication rate is lower. Overall hospital costs in laparoscopic
      repair are lower than or equivalent to the cost of open repair. Many variables
      come into play in these costs. The modification of any of these cost variables
      will influence overall costs of either procedure. To determine the economic
      consequences of choices made in surgery, all surgeons must evaluate the costs
      generated by their practice and compare the results to published data.

PMID- 18065922
TI  - [Inguinal hernia. What are the criteria for assessing the result of hernia
      repair?].
AB  - The assessment criteria reflect the questions patients ask at the preoperative
      visit: Is it painful? How long will the operation last? How long will I be
      hospitalized? How long until I can resume daily activities? What is the risk of
      recurrence? Is there a risk of long-term disability? Inguinal hernia repair is of
      one of the most widely assessed surgical procedures, even for more recent
      procedures: three Cochrane databases, eight meta-analyses and nearly 100
      prospective randomized trials cover this topic. Many facts are now established:
      There are significantly more recurrences after suture than after mesh techniques;
      for mesh, there is no difference between laparoscopic and conventional
      approaches.

PMID- 18065923
TI  - [What are the traps of incisional hernia open repair?].
AB  - Open repair of incisional hernia is a simple surgery. Nevertheless, uncountable
      traps wait for the operator during surgery. They mark out all the stages of the
      procedure, from incision to skin closure. They are source of intraoperative
      incidents and postoperative complications. Some of these complications could be
      very serious and require removing the prosthesis. To avoid these incidents and
      these complications, the surgeon has to remain watchful throughout the procedure
      and has to anticipate all the traps that could arise.

PMID- 18065924
TI  - [The Grenelle of MR contrast agents?].

PMID- 18065925
TI  - [MRI and DCIS, the end of a dogma?].

PMID- 18065926
TI  - [The rotator interval: hidden lesions?].
AB  - The rotator interval corresponds to a defined triangular shaped anatomical region
      at the anterosuperior portion of the shoulder where specific pathological
      processes may occur. First, the morphological and functional anatomy of the
      region will be reviewed. Then, the role of different imaging modalities will be
      described along with pathological imaging features. Normal structures of the
      rotator interval may be imaged with modern techniques, including MR and CT
      arthrography. On the other hand, clinical evaluation of rotator interval
      pathology remains difficult; and no consensus exists concerning their management.
      Imaging characterization of rotator interval pathology could be a key factor for
      pre-therapeutic work-up.

PMID- 18065927
TI  - [Tumors of the rectum: MRI and CT features].
AB  - The imaging features of rectal tumors on CT and MRI are reviewed. MRI is the
      imaging modality of choice for loco-regional staging, and may provide clues as to
      the histological nature of some tumors.

PMID- 18065928
TI  - [Pineapple juice as a negative oral contrast agent in magnetic resonance
      cholangiopancreatography].
AB  - PURPOSE: The quality of magnetic resonance cholangiopancreatography (MRCP) images
      is frequently degraded by high signal from the gastrointestinal tract on heavily
      T2W images. The purpose of this study is to evaluate pineapple juice (PJ) as an
      oral negative contrast agent in MRCP. MATERIALS AND METHODS: Results from MRCP in
      50 patients with PJ and 50 patients with paramagnetic contrast (ferumoxsil
      Lumirem) were compared. Reviewers were blinded to the type of contrast agent.
      Exam quality was recorded with regards to signal suppression in the stomach,
      duodenum and proximal small bowel and with regards to pancreatic duct and biliary
      ducts visualization. In vitro, the signal characteristics of several commercially
      available brands of PJ were assessed using T1W, T2W and MRCP sequences. Signal
      intensity was correlated with the manganese concentration measured using atomic
      absorption spectrometry. Finally, the reviewers compared the taste of PJ and
      ferumoxsil. RESULTS: On MRCP sequences, results were similar with regards to
      signal suppression in the stomach, duodenum and proximal small bowel with PJ and
      ferumoxsil. Visualization of the pancreatic duct, intrahgepatic bile ducts and
      CBD was similar with PJ and ferumoxsil. The signal intensity of commercially
      available brands of PJ on T2W and MRCP sequences correlated well with the
      measured manganese concentration on spectroscopy. Variations in manganese
      concentration were observed, with values ranging from 3.65 to 27.24 mg/L. The
      reviewers noted that PJ tasted "good" or "very good" and that ferumoxsil tasted
      "bad" or "very bad". CONCLUSION: Ingestion of PJ provides effective signal
      suppression in the GI tract on MRCP, similar to paramagnetic contrast agents.
      Because manganese concentration is highly variable in commercially available PJ
      brands, a brand with high manganese concentration should be selected.

PMID- 18065929
TI  - [MDCT urography with and without use of diuretics].
AB  - PURPOSE: To optimize the MDCT urogram protocol for assessment of the upper
      tracts. To assess the value of furosemide injection. MATERIALS AND METHODS:
      Prospective study comparing excretory phase imaging at 450 seconds in 67 patients
      assigned to 3 groups: a group without furosemide (f=0), a group with 20 mg
      furosemide (f=20), and a group with 10 mg furosemide (f=10). 3D MIP images were
      generated. Two experienced radiologists blinded to protocol specifications
      analyzed the quality of opacification the upper tracts, divided in 8 segments and
      urine density at the renal pelvis. RESULTS: The injection of 20 mg of furosemide
      significantly improved the opacification of the upper tracts with complete or
      near complete opacification in 82.6% of cases compared to 43.5% and 19% for the
      F=10 and f=0 groups respectively. Density measurements were 5 times less for the
      f=20 and f=10 groups compared to the f=0 group. CONCLUSION: Furosemide is useful
      for MDCT urography by improving upper tract opacification and filling: the
      reduced contrast concentration in the better distended and fully filled upper
      tracts improves evaluation of ureteral lumen and wall abnormalities.

PMID- 18065930
TI  - [Fractures of the ankylosed spine: MRI features].
AB  - The diagnosis of transverse spinal fractures in patients with ankylosing
      spondylitis and Forestier's disease (DISH) may be difficult. The MRI features of
      9 such fractures at the disk, vertebral body, spinal canal and posterior elements
      are presented. Fractures of the posterior elements (posterior arch fractures
      and/or rupture of interspinous or supraspinous ligaments and contiguous soft
      tissue structures) were present in all cases, underscoring the importance of MR
      signal abnormalities of posterior structures for diagnosis of these fractures. MR
      is advantageous due to its ability to demonstrate signal abnormalities of the
      posterior elements, which combined with disk and vertebral body abnormalities,
      play a major role for accurate diagnosis of this type of fracture.

PMID- 18065931
TI  - [Type III endoleaks at follow-up of covered descending thoracic aortic stent
      grafts: report of 3 patients].
AB  - PURPOSE: To describe the imaging work-up and management of type III endoleaks
      detected after covered stent-graft treatment of descending thoracic aortic
      aneurysms. PATIENTS AND METHODS: Retrospective study of circumstances surrounding
      the diagnosis, management and outcome type III endoleaks occuring in 3 of 18
      patients following covered stent-graft treatment of descending thoracic aortic
      aneurysms between April 1998 and July 2005. The endoleaks were detected at a mean
      follow-up of 22 months (19-24 months) after stent-graft placement. RESULTS: The
      type III endoleaks were detected on scheduled follow-up CT examinations in
      asymptomatic patients. Endovascular management was proposed at a mean interval
      time of 4.4 months (1 week - 11 months) after diagnosis of the endoleak, and was
      successful in all 3 cases. One patient died 1 month after endovascular repeai of
      the leak, 1 patient required surgical management at 14 months for new recurrence,
      and 1 patient had a favorable outcome at 2 months. CONCLUSION: Follow-up of
      patients after covered stent-graft treatment of descending thoracic aortic
      aneurysms is required. Prompt endovascular repair of delayed complications may be
      possible, but surgical management may become necessary.

PMID- 18065932
TI  - [Duplication of the common bile duct: MRI features].

PMID- 18065933
TI  - [Rupture of a mucoid cyst of the posterior cruciate ligament: a case report].

PMID- 18065934
TI  - [Cervico-facial hydatid disease: a case report].

PMID- 18065936
TI  - [Odontogenic keratocyst].

PMID- 18065935
TI  - [Misleading clinical and imaging features of abdominal tuberculosis: report of 2
      cases].

PMID- 18065937
TI  - [Answer to september e-quid].

PMID- 18065939
TI  - [New ultrasound applications in oncology].

PMID- 18065940
TI  - [Recent advances in contrast-enhanced ultrasound for oncology applications].
AB  - The combined use of high-end ultrasound units and sonographic contrast agents
      provide valuable information for lesion characterization and follow-up of
      patients under targeter treatments, especially oncologic patients. Early
      published results for liver pathology have created a place for this technique as
      a reference method leading to the publication of European guidelines. New
      oncologic applications have emerged over the last several years for lesions
      accessible by ultrasound with varied diagnostic value based on each target organ.
      Contrast-enhanced sonography is rapidly gaining ground for the follow-up of
      patients under targeted treatment, physical or drug induced, with major
      implications for the validation of concepts, and management of patients based on
      reliable early evaluation of therapeutic response to treatment. The purpose of
      this paper is to review recent advances in this field of sonographic imaging to
      better understand the role of ultrasound in oncologic pathology.

PMID- 18065941
TI  - [Tissue attenuation in small animals on contrast enhanced ultrasound].
AB  - Despite recent advances in contrast-enhanced ultrasound imaging, evaluation of
      tissue perfusion with contrast-enhanced ultrasound is still impaired by shadowing
      effects. These effects are particularly relevant in small animal studies due to
      high frequency imaging. Current methods of tissue attenuation correction are not
      suited for contrast-enhanced ultrasound examinations, because microbubble
      acoustic response to ultrasound waves is far more complex than that of tissues. A
      method allowing in vivo tissue attenuation correction in the presence of contrast
      agents is presented.

PMID- 18065942
TI  - [Sonopermeabilization: therapeutic alternative with ultrasound and microbubbles].
AB  - Future applications of ultrasound and microbubbles extend to more than imaging
      applications. Over the last few years, it was reported that sonographic contrast
      agent effects under ultrasound, modulate transiently cell membrane permeability.
      This process, named sonoporation and classified as a new physical method to
      transfer genes or drugs, consists of using a physical energy source to modulate
      membrane integrity. The possibility to transfer therapeutic genes would be a new
      tool for gene therapy and could constitute an alternative method. After in vitro
      and in vivo studies presentation, the therapeutic potential of sonoporation will
      be investigated in this paper.

PMID- 18065943
TI  - [Therapies by focused ultrasound].
AB  - Many techniques of thermotherapy have emerged over the last several years in the
      field of oncology using different types of physical agents, including ultrasound.
      Only ultrasound can target deep seated lesions non-invasively without need for
      percutaneous probe insertion. Depending on their utilization, it is possible to
      select either thermal effects, in a continuous mode, at low temperature (allowing
      thermo-induced biological effects) or at high temperature (allowing
      thermoablation), or mechanical effects, in a pulsed mode, at low energy level
      (allowing biological effects) or at high energy levels (histotripsy).
      Thermoablation by focused ultrasound is now developing fast for applications in
      many organs. It gained a well defined role for the treatment of prostatic cancer
      and uterine leiomyoma but needs to be better evaluated in other organs such as
      the breast. Treatment of abdominal tumors must still be considered as
      experimental as long as problems related to acoustic interfaces (produced by ribs
      and gas) and movement correction are not resolved. Biological applications of
      focused ultrasound are currently being explored and have a great long term
      potential.

PMID- 18065944
TI  - [Ultrasonic arrays: new therapeutic developments].
AB  - Bursts of focused ultrasound energy a billion times more intense than diagnostic
      ultrasound have become a non-invasive option for tumor ablation, from prostate
      cancer to uterine fibroid, during the last decade. Despite this progress, many
      issues still need to be addressed. First, for brain targeting, the correction of
      distortions induced by the skull remains today a technological achievement that
      still needs to be validated clinically. Secondly, the problem of motion artifacts
      for abdominal treatments becomes today an important research topic. For all these
      issues, the potential of new ultrasonic therapy devices able to work both in
      Transmit and Receive modes will be emphasized and clinical results on monkeys and
      pigs will be presented.

PMID- 18065945
TI  - [A tumour-mimic pig liver model for guiding focused ultrasound thermal ablation].
AB  - There is no established liver tumour model in pigs to study the efficacy of
      ablative treatment options available for the treatment of liver tumours by
      physical agents. A tumour-mimic model visible with high contrast on sonograms and
      on gross pathology has been studied at mid-term on 20 pigs. The aim was to
      determine if these tumour-mimics are well tolerated and can be used to validate
      the use of thermal therapies at a preclinical stage. The dimensions of the tumour
      mimics measured on sonograms were reproducible (diameter: 9.6 +/- 1.9 mm) and
      correlated with those performed in gross pathology (R(2)=0.73). The accuracy of
      focused ultrasound thermal therapy can be evaluated preclinically using these
      tumour-mimics.

PMID- 18065946
TI  - [Ultrasound interstitial mini invasive probes for thermal ablation in liver:
      feasibility study in vivo].
AB  - High intensity ultrasounds are routinely used for thermal ablation of some
      cancers. However, for treating hepatic tumours with physical agents, RF
      applicators and cryoprobes are still preferred. The goal of the present study was
      to demonstrate the feasibility of using interstitial ultrasound probes in liver
      following two approaches: percutaneous and intra-tissular or endo vascular. In
      vivo trials on a porcine model demonstrated the minimally invasive nature of both
      procedures. Homogeneous and reproducible thermal lesions, up to 20 mm deep, were
      obtained. The work on these two original approaches deserves to be completed with
      more extended prospective studies. The association with an imaging method will
      have to be studied before proceeding to clinical trials.

PMID- 18065947
TI  - [Biological tissue strain imaging with freehand elastography].
AB  - An imaging technique of deformation under load of a biological soft tissue, from
      numerical processing of radiofrequency ultrasound images is presented. The 2D
      locally regularized estimation method determines deformation parameters as the
      arguments that maximize a similarity criterion between a pre-compression region
      and its deformed version, compensated for according to these parameters. The
      technique was assessed with ultrasound data acquired during freehand scanning on
      two dedicated elastography phantoms as well as ex vivo bovine liver samples,
      containing artificial lesions made with agar gel. Although the load conditions
      are complex, elastograms are easy to interpret, exhibiting the inclusions with
      sharp boundaries.

PMID- 18065948
TI  - Dopamine-imprinted polymers: template-monomer interactions, analysis of template
      removal and application to solid phase extraction.
AB  - A dopamine-imprinted polymer (MIP) was prepared in aqueous methanol solution at
      60(o)C by free-radical cross-linking polymerization of methacrylic acid in the
      presence of ethylene glycol dimethacrylate as the cross-linker and dopamine
      hydrochloride as the template molecule. Its ability to isolate dopamine was
      evaluated as the basis of a solid phase extraction procedure and compared with
      that of a non-imprinted polymer(NIP). The binding of dopamine was 84.1% and 29.1%
      for MIP and NIP, respectively. Various reported post-polymerization treatments to
      reduce template bleeding were examined. In our case the lowest bleeding was
      achieved after applying a combined procedure: continuous extraction in a Soxhlet
      apparatus (CE), followed by microwave-assisted extraction (ME) to a level of
      0.061 microg/mL. A simplified model of the template-monomer complexes allowed
      rationalization of monomer choice based on the heats of complex formation at a
      PM3 level of theory.

PMID- 18065949
TI  - Synthesis and bioevaluation of 5-fluorouracil derivatives.
AB  - A series of six novel 5-fluorouracil derivatives 1-6 were synthesized and their
      structures confirmed by (1)H- and (13)C-NMR, MS and elemental analysis. The
      preliminary in vitro antitumor activities against B16, K562 and CHO cells and the
      in vivo inhibitions of liver cancer H(22) demonstrated that some of these
      compounds effectively inhibit the growth of tumor cells, but the in vivo trials
      in mice revealed that the compounds also exhibited serious liver and lung tissue
      toxicity. The hydrolysis experiments indicated that this type of compound did not
      readily liberate 5-fluorouracil, as expected.

PMID- 18065950
TI  - Syntheses of calix[4]pyrroles by amberlyst-15 catalyzed cyclocondensations of
      pyrrole with selected ketones.
AB  - A facile and efficient protocol is reported for the synthesis of calix[4]pyrroles
      and N-confused calix[4]pyrroles in moderate to excellent yields by reaction of
      dialkyl or cycloalkyl ketones with pyrrole catalyzed by reusable Amberlyst(TM)-15
      under eco-friendly conditions.

PMID- 18065951
TI  - Synthesis and biological activity of N-substituted-3-chloro-2-azetidinones.
AB  - 2-Aminobenzothiazole-6-carboxylic acid (1), on condensation with chloroacetyl
      chloride yielded 2-(2-chloroacetylamino)benzothiazole-6-carboxylic acid (2),
      which on amination with hydrazine hydrate yielded in turn 2-(2
      hydrazinoacetylamino)benzo-thiazole-6-carboxylic acid (3). Compound 3, on
      condensation with various aromatic aldehydes afforded a series of 2-{2-[N'
      (arylidene)hydrazino]acetylamino}benzothiazole-6-carboxylic acids 4a-h, which
      upon dehydrative annulation in the presence of chloroacetyl chloride and
      triethylamine yielded 2-{2-[3-chloro-2-(aryl)-4-oxoazetidin-1-ylamino]
      acetylamino}benzothiazole-6-carboxylic acids 5a-h. The synthesized compounds 4a-h
      and 5a-h were screened for their antibacterial activity against four
      microorganisms: Staphylococcus aureus (Gram positive), Bacillus subtilis (Gram
      positive), Psuedomonas aeruginosa (Gram negative) and Escherichia coli (Gram
      negative). They were found to exhibit good to moderate antibacterial activity.
      The antifungal activity of these compounds were also tested against three
      different fungal species. None of them were active against the species tested.

PMID- 18065952
TI  - A novel synthesis of bromobenzenes using molecular bromine.
AB  - Certain substituted bromobenzenes have been synthesized in acceptable yields
      using a novel Sandmeyer type reaction. The reactions are relatively quick and
      possibly proceed via a radical mechanism.

PMID- 18065954
TI  - Synthesis and molecular structure of ethyl [N-tosyl-(R)-prolyloxy]-2(S)-[4-cyano
      8,8-ethylenedioxy-5-oxo-5,6,7,8-tetrahydroindolizin-3-yl] acetate, a key
      intermediate in the total synthesis of (20S)-camptothecins.
AB  - The synthesis of optically active [N-tosyl-(R)-prolyloxy]-2(S)-[4-cyano-8,8
      ethylenedioxy-5-oxo-5,6,7,8-tetrahydroindolizin-3-yl] acetate (4a), a key
      intermediate for the total asymmetric synthesis of 20(S)-camptothecin anticancer
      drugs, is described. Its structure was characterized by 2D-NMR techniques and the
      absolute configuration was further confirmed for the first time by X-ray crystal
      structure analysis.

PMID- 18065953
TI  - Cyclization-activated prodrugs.
AB  - Many drugs suffer from an extensive first-pass metabolism leading to drug
      inactivation and/or production of toxic metabolites, which makes them attractive
      targets for prodrug design. The classical prodrug approach, which involves enzyme
      sensitive covalent linkage between the parent drug and a carrier moiety, is a
      well established strategy to overcome bioavailability/toxicity issues. However,
      the development of prodrugs that can regenerate the parent drug through non
      enzymatic pathways has emerged as an alternative approach in which prodrug
      activation is not influenced by inter- and intraindividual variability that
      affects enzymatic activity. Cyclization-activated prodrugs have been capturing
      the attention of medicinal chemists since the middle-1980s, and reached maturity
      in prodrug design in the late 1990 s. Many different strategies have been
      exploited in recent years concerning the development of intramoleculary-activated
      prodrugs spanning from analgesics to anti-HIV therapeutic agents. Intramolecular
      pathways have also a key role in two-step prodrug activation, where an initial
      enzymatic cleavage step is followed by a cyclization-elimination reaction that
      releases the active drug. This work is a brief overview of research on
      cyclization-activated prodrugs from the last two decades.

PMID- 18065955
TI  - Comparative study of regioselective synthesis of beta-aminoalcohols under
      solventless conditions catalyzed by sulfated zirconia and SZ/MCM-41.
AB  - Sulfated zirconia and SZ/MCM-41 were used as catalysts for the synthesis of beta
      aminoalcohols via epoxide aminolysis. Sulfated zirconia was prepared by sol-gel
      and SZ/MCM-41 was obtained by impregnation. Solid catalysts were characterized by
      XRD, SEM-EDS, UV-Vis, FT-IR pyridine desorption and Nitrogen physisorption. Both
      acid materials were useful as catalysts, even when they were recycled several
      times. The beta-aminoalcohols were characterized by FT-IR, (1)H- and (13)C-NMR
      and GC-MS.

PMID- 18065956
TI  - Synthesis of new L-ascorbic ferulic acid hybrids.
AB  - A feasibility and chemical study of the coupling conditions of L-ascorbic acid
      with ferulic acid derivatives are described on the basis of the known synergistic
      effects of mixtures of various antioxidants. Novel L-ascorbic ferulic hybrids
      linked at the C-3 hydroxyl group were prepared with the aim to protect the
      alcohol function and the enediol system.

PMID- 18065957
TI  - Hantzsch synthesis of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-methoxyphenyl)-1,4
      dihydropyridine; a novel cyclisation leading to an unusual formation of 1-amino-2
      methoxy-carbonyl-3,5-bis(o-methoxyphenyl)-4-oxa-cyclohexan-1-ene.
AB  - Hantzsch condensation of two equivalents of methyl-3-aminocrotonate with (m- and
      p)-methoxybenzaldehyde afforded the expected products 2,6-dimethyl-3,5
      dimethoxycarbonyl-4-(m-methoxyphenyl)-1,4-dihydropyridine and 2,6-dimethyl-3,5
      dimethoxycarbonyl-4-(p-methoxyphenyl)-1,4-dihydropyridine, whereas o-methoxy
      benzaldehyde produced mainly 1-amino-2-methoxycarbonyl-3,5-bis(o-methoxy-phenyl)
      4-oxa-cyclohexan-1-ene. The structure of the product, not previously reported in
      the literature, was determined by 1D and 2D NMR spectra and its MS fragmentation.
      This is the first example of cyclisation leading to a substituted pyran rather
      than 1,4-DHP under typical Hantzsch reaction conditions. A plausible mechanism
      for its formation is postulated.

PMID- 18065958
TI  - The drug release profile from calcium-induced alginate gel beads coated with an
      alginate hydrolysate.
AB  - Calcium-induced alginate gel bead (Alg-Ca) coated with an alginate hydrolysate
      (Alg), e.g. the guluronic acid block (GB) was prepared and the model drug,
      hydrocortisone release profiles were investigated under simulated
      gastrointestinal conditions. Their molecular weights were one sixth or one tenth
      that of Alg and the diffraction patterns of the hydrolysates resembled that of
      Alg. The drug release rate from Alg-Ca coated with GB apparently lowered than
      that of Alg-Ca (coating-free) in the gastric juice (pH1.2). And the coating did
      not resist the disintegration of Alg-Ca in the intestinal juice (pH 6.8) and the
      gel erosion accelerated the drug release. On the other hand, for the coated Alg
      Ca containing chitosan, the drug release showed zero-order kinetics without rapid
      erosion of Alg-Ca. The drug release rate from Alg-Ca was able to be controlled by
      the coating and modifying the composition of the gel matrix.

PMID- 18065959
TI  - Microcystic adnexal carcinoma: an immunohistochemical reappraisal.
AB  - Even though immunohistochemical comparisons of microcystic adnexal carcinoma vs
      infiltrative basal cell carcinoma and desmoplastic trichoepithelioma exist, they
      are mostly restricted to the use of a single stain. In addition, a comparison
      with squamous cell carcinoma has not been reported previously. In this study, we
      compare the expression of cytokeratin (CK) 15, CK7, CK20, CK903, carcinoembryonic
      antigen (CEA), CD10, CD15 and BerEP4 in 13 microcystic adnexal carcinoma, eight
      desmoplastic trichoepithelioma, 10 infiltrative basal cell carcinoma, and eight
      squamous cell carcinoma of which five exhibited ductal differentiation. We found
      that the majority of microcystic adnexal carcinoma (92%) and desmoplastic
      trichoepithelioma (100%) cases expressed CK15 while the infiltrative basal cell
      carcinoma and squamous cell carcinoma cases were all negative. Forty percent of
      infiltrative basal cell carcinoma expressed CK7; while only two microcystic
      adnexal carcinoma cases (15%) and one squamous cell carcinoma with ductal
      differentiation (12%) expressed CK7 in the remaining three tumor categories. None
      of the desmoplastic trichoepithelioma expressed CK7. All tumors were strongly
      positive for CK903. While the neoplastic cells were negative, luminal staining of
      ductal structures was noted for CK7, CD15 and CEA in some of the microcystic
      adnexal carcinoma, desmoplastic trichoepithelioma and squamous cell carcinoma
      with ductal differentiation cases. Sixty percent of infiltrative basal cell
      carcinoma, 31% of microcystic adnexal carcinoma, and 25% of squamous cell
      carcinoma express CD10. BerEP4 expression was noted in 38% of microcystic adnexal
      carcinoma, 57% of desmoplastic trichoepithelioma, 100% of infiltrative basal cell
      carcinoma, and 38% of squamous cell carcinoma. In conclusion, we found CK15 to be
      a useful marker in distinguishing microcystic adnexal carcinoma from infiltrative
      basal cell carcinoma and squamous cell carcinoma with ductal differentiation. Our
      experience indicates that microcystic adnexal carcinoma and desmoplastic
      trichoepithelioma have a similar immunohistochemical profile that is, CK15+ and
      BerEP4+/-; thus, additional studies are needed to separate these two entities.

PMID- 18065960
TI  - MSH-6: extending the reliability of immunohistochemistry as a screening tool in
      Muir-Torre syndrome.
AB  - The subtype of Muir-Torre syndrome, allelic to hereditary nonpolyposis colorectal
      cancer is typically associated with germline mutations in the mismatch repair
      proteins MSH-2 and/or MLH-1. More recently, mutation in an additional mismatch
      repair protein MSH-6 has been documented in a patient with Muir-Torre syndrome.
      Given this, the aim of the present study was to ascertain the frequency of the
      same in unselected sebaceous gland neoplasms. Overall, we found that 59% of
      sebaceous neoplasms exhibited a mutation in at least one mismatch repair protein
      gene -- a prevalence rate similar to that reported previously by others. Of
      interest, we found MSH-6 to be the mismatch repair protein most commonly lost
      17/41 (41%), followed by MSH-2 14/41 (34%) and MLH-18/41 (20%) and the positive
      predictive value of each were as follows: MLH-1 88%, MSH-6 67% and MSH-2 55%. The
      frequency of a MSH-6 germline mutation in our cohort indicates that it is not a
      rare finding. Evidence indicating microsatellite stability in three of 17
      patients with a clinical history indicative of Muir-Torre syndrome and a mutation
      in only MSH-6 suggests that the phenotype of a germline MSH-6 mutation differs
      from that of MLH-1 and MSH-2 mutations and further supports the use of
      immunohistochemistry as a screening tool in patients with Muir-Torre syndrome
      with an extended panel that includes MSH-6.

PMID- 18065961
TI  - Mapping of TMPRSS2-ERG fusions in the context of multi-focal prostate cancer.
AB  - TMPRSS2-ERG gene fusion leading to the androgenic induction of the ERG proto
      oncogene expression is a highly prevalent oncogenic alteration in prostate tumor
      cells. Prostate cancer is a multi-focal disease, and the origins as well as
      biological contribution of multiple cancer foci remain unclear with respect to
      prostate cancer onset or progression. To assess the role of TMPRSS2-ERG
      alteration in prostate cancer onset and/or progression, we have evaluated the
      status of fusion transcripts in benign glands, prostatic intraepithelial
      neoplasia (PIN) and multiple cancer foci of each prostate. Quantitative
      expression of TMPRSS2-ERG fusion type A and C transcripts was analyzed in benign,
      tumor and PIN areas, selected from whole-mount radical prostatectomy slides.
      TMPRSS2-ERG expression was correlated with clinicopathological features. Overall,
      30 of 45 (67%) patients exhibited TMPRSS2-ERG fusion transcripts in at least one
      tumor focus. Of 80 tumor foci analyzed, 39 had TMPRSS2-ERG fusion (type A only:
      30, type C only: 2, both types A and C: 7), with predominant detection of the
      TMPRSS2-ERG fusion type A (27/30, 90%) in the index tumors. Of 14 PIN lesions, 2
      were positive for type A fusion. Frequent presence of the TMPRSS2-ERG in index
      tumors suggests critical roles of ERG alterations in the onset and progression of
      a large subset of prostate cancer. However, heterogeneity of the TMPRSS2-ERG
      detection in the context of multiple cancer foci and its frequency in PIN also
      support the role of other genomic alterations in the origins of prostate cancer.

PMID- 18065963
TI  - Destructive dentistry.

PMID- 18065964
TI  - Updated guidelines.

PMID- 18065965
TI  - Virtually impossible.

PMID- 18065966
TI  - Re: Research governance.

PMID- 18065967
TI  - Hidden pathology.

PMID- 18065979
TI  - Link between oral cancer and ethnicity.

PMID- 18065980
TI  - Conscious sedation for dentistry: an update.
AB  - Despite its excellent safety record there remains disquiet about the provision of
      conscious sedation for dental care. This applies particularly to the use of
      'alternative' sedation techniques which extend beyond the 'standard' techniques
      (intravenous midazolam for adults and nitrous oxide/oxygen) described in
      Conscious sedation in the provision of dental care (2003). New guidance from the
      Faculty of Dental Surgery of the Royal College of Surgeons of England and the
      Royal College of Anaesthetists develops the earlier guidance to encompass the use
      of alternative sedation drugs and techniques. It has been prepared for dental and
      medical practitioners (including anaesthetists) and their teams and defines the
      minimum standard for safe and effective patient care whatever the clinical
      setting.

PMID- 18065981
TI  - Diagnosis and management of the infraerupted primary molar.
AB  - An infraerupted tooth is a tooth that has failed to erupt to be in line with
      adjacent teeth in the vertical plane of occlusion. The general dentist may be
      faced with this predicament which requires careful attention and thoughtful
      consideration in terms of long-term patient goals. It is important to diagnose
      infraerupted teeth and treat them in a timely fashion to help prevent unwelcome
      sequelae. Important interdisciplinary communication is vital between the dentist
      and the orthodontist to ensure that precious space and time are not lost. Here we
      present a review article of complications and considerations that must be taken
      into account when faced with a patient who has an infraerupted tooth.

PMID- 18065982
TI  - Radiographic evidence of postoperative healing 12 years following root canal
      treatment--a case report.
AB  - A case with evidence of radiographic healing of a periapical lesion 12 years
      after root canal treatment is presented. The use and limitations of previously
      produced guidelines on radiographic follow-up intervals are discussed. Questions
      are raised about what is known of the healing process and when further treatment
      should be instituted. The reliance on single radiographs alone when making
      treatment decisions is discouraged.

PMID- 18065983
TI  - Bisphosphonate osteonecrosis of the jaws; an increasing problem for the dental
      practitioner.
AB  - Osteonecrosis of the jaws is an increasingly recognised complication of
      bisphosphonate therapy. Although this has generated a large amount of literature
      in the last few years, it is difficult to know how the complications associated
      with bisphosphonates are impacting on general dental practitioners (GDPs).
      Bisphosphonates are commonly prescribed in the management of osteoporosis,
      hypercalcemia and multiple myeloma. The risk of osteonecrosis in patients taking
      bisphosphonates is low but difficult to quantify. The risk associated with oral
      therapy is in the order of 0.01% although with parenteral therapy it may be as
      high as 10%. Associated factors in the development of osteonecrosis include poor
      dental health, odontogenic infection and invasive dental treatment. Guidelines on
      managing patients who are currently taking or have previously taken
      bisphosphonates have not yet been published in the UK. The management of patients
      relies on existing experience in managing patients with apparently similar
      conditions such as osteoradionecrosis. Most GDPs do not routinely make specific
      efforts to identify patients who have taken bisphosphonates, and as patients may
      be poor at providing such information voluntarily, it is likely that many
      patients are currently not identified when they attend general dental practice.
      The dental management of patients with a history of bisphosphonate treatment is
      based around prevention and minimally traumatic treatment. Failure to recognise
      these patients and manage them appropriately could contribute to the development
      of osteonecrosis, which can be very difficult to manage.

PMID- 18065984
TI  - The role of the dental team in responding to domestic violence.
AB  - The face is a common target in assault and consequently the dentist and dental
      care professional has a part to play in identifying domestic violence. Domestic
      violence is a term which refers to a wide range of physical, sexual, emotional
      and financial abuse of people who are, or have been, intimate partners - whether
      or not they are married or cohabiting. Although domestic violence can take place
      in any intimate relationship, including gay and lesbian partnerships, and whilst
      abuse of men by female partners does occur, the great majority and the most
      severe incidents of domestic violence, are perpetrated by men against women and
      we have therefore elected refer to the victim of assault in this paper as 'she'
      for ease of writing.

PMID- 18066007
TI  - Stop the cull. Animal vaccines prevent disease but founder because of political
      motivations.

PMID- 18066008
TI  - Another inconvenient truth. In Europe, no one apparently wants to listen if you
      have good news about genetically modified organisms (GMOs).

PMID- 18066009
TI  - Pfizer dumps Exubera.

PMID- 18066010
TI  - Proposed changes to patent code loom over biotech industry.

PMID- 18066011
TI  - Biogen Idec goes on the auction block.

PMID- 18066012
TI  - Chinese manufacturers vie for piece of outsourcing pie.

PMID- 18066014
TI  - Biotech patents still strong.

PMID- 18066015
TI  - Pipelines turn to biotech.

PMID- 18066016
TI  - Biotech for your companion?

PMID- 18066017
TI  - GM soybeans--revisiting a controversial format.

PMID- 18066018
TI  - GM soybeans--revisiting a controversial format.

PMID- 18066019
TI  - GM soybeans--revisiting a controversial format.

PMID- 18066020
TI  - GM soybeans--revisiting a controversial format.

PMID- 18066021
TI  - GM soybeans--revisiting a controversial format.

PMID- 18066022
TI  - Response to GM soybeans-revisiting a controversial format.

PMID- 18066023
TI  - GM soybeans--revisiting a controversial format.

PMID- 18066025
TI  - Bridging the knowledge gaps in vaccine design.

PMID- 18066026
TI  - Fungal bioinsecticide with a sting.

PMID- 18066027
TI  - Isotype selection in antibody engineering.

PMID- 18066029
TI  - Beyond interferon.

PMID- 18066031
TI  - Hepatitis C: staying the course.

PMID- 18066032
TI  - Systems biology and the host response to viral infection.

PMID- 18066033
TI  - Antivirals--an increasingly healthy investment.

PMID- 18066034
TI  - Antivirals become a broader enterprise.

PMID- 18066035
TI  - Patentability issues surrounding antivirals.

PMID- 18066037
TI  - Bioinformatics prediction of HIV coreceptor usage.

PMID- 18066038
TI  - Albinterferon alpha-2b: a genetic fusion protein for the treatment of chronic
      hepatitis C.
AB  - Treatment regimens based on the use of interferon-alpha (IFN-alpha) remain the
      cornerstone of therapy for chronic hepatitis C virus infection, which affects
      nearly 170 million people worldwide. Treatment options include unmodified IFN
      alpha given three times weekly or pegylated IFNs given once weekly. The albumin
      fusion platform takes advantage of the long half-life of human albumin to provide
      a new treatment approach that allows the dosing frequency of IFN-alpha to be
      reduced in individuals with chronic hepatitis C. Albinterferon alpha-2b (alb
      IFN), a recombinant polypeptide composed of IFN-alpha2b genetically fused to
      human albumin, has an extended half-life and early evidence indicates that it is
      efficacious and well tolerated. Pharmacodynamic modeling supports treatment with
      alb-IFN at 2- or 4-week intervals. Phase 3 registration trials are in progress.
      The albumin-fusion platform is currently being applied to other important
      bioactive peptides with short half-lives. These fusion proteins, which are at
      present in different phases of clinical development, might lead to improved
      therapies across a broad range of diseases.

PMID- 18066039
TI  - The growth and potential of human antiviral monoclonal antibody therapeutics.
AB  - Monoclonal antibodies (mAbs) have long provided powerful research tools for
      virologists to understand the mechanisms of virus entry into host cells and of
      antiviral immunity. Even so, commercial development of human (or humanized) mAbs
      for the prophylaxis, preemptive and acute treatment of viral infections has been
      slow. This is surprising, as new antibody discovery tools have increased the
      speed and precision with which potent neutralizing human antiviral mAbs can be
      identified. As longstanding barriers to antiviral mAb development, such as
      antigenic variability of circulating viral strains and the ability of viruses to
      undergo neutralization escape, are being overcome, deeper insight into the
      mechanisms of mAb action and engineering of effector functions are also improving
      the efficacy of antiviral mAbs. These successes, in both industrial and academic
      laboratories, coupled with ongoing changes in the biomedical and regulatory
      environments, herald an era when the commercial development of human antiviral
      mAb therapies will likely surge.

PMID- 18066040
TI  - RNA interference against viruses: strike and counterstrike.
AB  - RNA interference (RNAi) is a conserved sequence-specific, gene-silencing
      mechanism that is induced by double-stranded RNA. RNAi holds great promise as a
      novel nucleic acid-based therapeutic against a wide variety of diseases,
      including cancer, infectious diseases and genetic disorders. Antiviral RNAi
      strategies have received much attention and several compounds are currently being
      tested in clinical trials. Although induced RNAi is able to trigger profound and
      specific inhibition of virus replication, it is becoming clear that RNAi
      therapeutics are not as straightforward as we had initially hoped. Difficulties
      concerning toxicity and delivery to the right cells that earlier hampered the
      development of antisense-based therapeutics may also apply to RNAi. In addition,
      there are indications that viruses have evolved ways to escape from RNAi. Proper
      consideration of all of these issues will be necessary in the design of RNAi
      based therapeutics for successful clinical intervention of human pathogenic
      viruses.

PMID- 18066046
TI  - Management consulting for scientists.

PMID- 18066041
TI  - Genetic therapies against HIV.
AB  - Highly active antiretroviral therapy prolongs the life of HIV-infected
      individuals, but it requires lifelong treatment and results in cumulative
      toxicities and viral-escape mutants. Gene therapy offers the promise of
      preventing progressive HIV infection by sustained interference with viral
      replication in the absence of chronic chemotherapy. Gene-targeting strategies are
      being developed with RNA-based agents, such as ribozymes, antisense, RNA aptamers
      and small interfering RNA, and protein-based agents, such as the mutant HIV Rev
      protein M10, fusion inhibitors and zinc-finger nucleases. Recent advances in T
      cell-based strategies include gene-modified HIV-resistant T cells, lentiviral
      gene delivery, CD8(+) T cells, T bodies and engineered T-cell receptors. HIV
      resistant hematopoietic stem cells have the potential to protect all cell types
      susceptible to HIV infection. The emergence of viral resistance can be addressed
      by therapies that use combinations of genetic agents and that inhibit both viral
      and host targets. Many of these strategies are being tested in ongoing and
      planned clinical trials.

PMID- 18066048
TI  - A receptor that mediates the post-mating switch in Drosophila reproductive
      behaviour.
AB  - Mating in many species induces a dramatic switch in female reproductive
      behaviour. In most insects, this switch is triggered by factors present in the
      male's seminal fluid. How these factors exert such profound effects in females is
      unknown. Here we identify a receptor for the Drosophila melanogaster sex peptide
      (SP, also known as Acp70A), the primary trigger of post-mating responses in this
      species. Females that lack the sex peptide receptor (SPR, also known as CG16752),
      either entirely or only in the nervous system, fail to respond to SP and continue
      to show virgin behaviours even after mating. SPR is expressed in the female's
      reproductive tract and central nervous system. The behavioural functions of SPR
      map to the subset of neurons that also express the fruitless gene, a key
      determinant of sex-specific reproductive behaviour. SPR is highly conserved
      across insects, opening up the prospect of new strategies to control the
      reproductive and host-seeking behaviours of agricultural pests and human disease
      vectors.

PMID- 18066049
TI  - Three-dimensional atomic-scale structure of size-selected gold nanoclusters.
AB  - An unambiguous determination of the three-dimensional structure of nanoparticles
      is challenging. Electron tomography requires a series of images taken for many
      different specimen orientations. This approach is ideal for stable and stationary
      structures. But ultrasmall nanoparticles are intrinsically structurally unstable
      and may interact with the incident electron beam, constraining the electron beam
      density that can be used and the duration of the observation. Here we use
      aberration-corrected scanning transmission electron microscopy, coupled with
      simple imaging simulation, to determine with atomic resolution the size, three
      dimensional shape, orientation and atomic arrangement of size-selected gold
      nanoclusters that are preformed in the gas phase and soft-landed on an amorphous
      carbon substrate. The structures of gold nanoclusters containing 3096 atoms can
      be identified with either Ino-decahedral, cuboctahedral or icosahedral
      geometries. Comparison with theoretical modelling of the system suggests that the
      structures are consistent with energetic considerations. The discovery that
      nanoscale gold particles function as active and selective catalysts for a variety
      of important chemical reactions has provoked much research interest in recent
      years. We believe that the detailed structure information we provide will help to
      unravel the role of these nanoclusters in size- and structure-specific catalytic
      reactions. We note that the technique will be of use in investigations of other
      supported ultrasmall metal cluster systems.

PMID- 18066050
TI  - Epigenetic memory of an active gene state depends on histone H3.3 incorporation
      into chromatin in the absence of transcription.
AB  - The remarkable stability of gene expression in somatic cells is exemplified by
      the way memory of an active gene state is retained when an endoderm cell nucleus
      is transplanted to an enucleated egg. Here we analyse the mechanism of a similar
      example of epigenetic memory. We find that memory can persist through 24 cell
      divisions in the absence of transcription and applies to the expression of the
      myogenic gene MyoD in non-muscle cell lineages of nuclear transplant embryos. We
      show that memory is not explained by the methylation of promoter DNA. However, we
      demonstrate that epigenetic memory correlates with the association of histone
      H3.3 with the MyoD promoter in embryos that display memory but not in those where
      memory has been lost. The association of a mutated histone H3.3 (H3.3 E4, which
      lacks the methylatable H3.3 lysine 4) with promoter DNA eliminates memory,
      indicating a requirement of H3.3 K4 for memory. We also show that overexpression
      of H3.3 can enhance memory in transplanted nuclei. We therefore conclude that the
      association of histone H3.3 with the MyoD promoter makes a necessary contribution
      to this example of memory. Hence, we suggest that epigenetic memory helps to
      stabilize gene expression in normal development; it might also help to account
      for the inefficient reprogramming in some transplanted nuclei.

PMID- 18066051
TI  - Pax7 activates myogenic genes by recruitment of a histone methyltransferase
      complex.
AB  - Satellite cells purified from adult skeletal muscle can participate extensively
      in muscle regeneration and can also re-populate the satellite cell pool,
      suggesting that they have direct therapeutic potential for treating degenerative
      muscle diseases. The paired-box transcription factor Pax7 is required for
      satellite cells to generate committed myogenic progenitors. In this study we
      undertook a multi-level approach to define the role of Pax7 in satellite cell
      function. Using comparative microarray analysis, we identified several novel and
      strongly regulated targets; in particular, we identified Myf5 as a gene whose
      expression was regulated by Pax7. Using siRNA, fluorescence-activated cell
      sorting (FACS) and chromatin immunoprecipitation (ChIP) studies we confirmed that
      Myf5 is directly regulated by Pax7 in myoblasts derived from satellite cells.
      Tandem affinity purification (TAP) and mass spectrometry were used to purify Pax7
      together with its co-factors. This revealed that Pax7 associates with the Wdr5
      Ash2L-MLL2 histone methyltransferase (HMT) complex that directs methylation of
      histone H3 lysine 4 (H3K4, refs 4-10). Binding of the Pax7-HMT complex to Myf5
      resulted in H3K4 tri-methylation of surrounding chromatin. Thus, Pax7 induces
      chromatin modifications that stimulate transcriptional activation of target genes
      to regulate entry into the myogenic developmental programme.

PMID- 18066052
TI  - Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark
      for transcriptional regulation.
AB  - Posttranslational modifications of histones such as methylation, acetylation and
      phosphorylation regulate chromatin structure and gene expression. Here we show
      that protein-kinase-C-related kinase 1 (PRK1) phosphorylates histone H3 at
      threonine 11 (H3T11) upon ligand-dependent recruitment to androgen receptor
      target genes. PRK1 is pivotal to androgen receptor function because PRK1
      knockdown or inhibition impedes androgen receptor-dependent transcription.
      Blocking PRK1 function abrogates androgen-induced H3T11 phosphorylation and
      inhibits androgen-induced demethylation of histone H3. Moreover, serine-5
      phosphorylated RNA polymerase II is no longer observed at androgen receptor
      target promoters. Phosphorylation of H3T11 by PRK1 accelerates demethylation by
      the Jumonji C (JmjC)-domain-containing protein JMJD2C. Thus, phosphorylation of
      H3T11 by PRK1 establishes a novel chromatin mark for gene activation, identifying
      PRK1 as a gatekeeper of androgen receptor-dependent transcription. Importantly,
      levels of PRK1 and phosphorylated H3T11 correlate with Gleason scores of prostate
      carcinomas. Finally, inhibition of PRK1 blocks proliferation of androgen receptor
      induced tumour cell proliferation, making PRK1 a promising therapeutic target.

PMID- 18066053
TI  - Disruption of KIF17-Mint1 interaction by CaMKII-dependent phosphorylation: a
      molecular model of kinesin-cargo release.
AB  - Establishment and maintenance of cell structures and functions are highly
      dependent on the efficient regulation of intracellular transport in which
      proteins of the kinesin superfamily (KIFs) are very important. In this regard,
      how KIFs regulate the release of their cargo is a critical process that remains
      to be elucidated. To address this specific question, we have investigated the
      mechanism behind the regulation of the KIF17-Mint1 interaction. Here we report
      that the tail region of the molecular motor KIF17 is regulated by
      phosphorylation. Using direct visualization of protein-protein interaction by
      FRET and various in vitro and in vivo approaches we have demonstrated that CaMKII
      dependent phosphorylation of KIF17 on Ser 1029 disrupts the KIF17-Mint1
      association and results in the release of the transported cargo from its
      microtubule-based transport.

PMID- 18066054
TI  - Multienzyme docking in hybrid megasynthetases.
AB  - Hybrid multienzyme systems composed of polyketide synthase (PKS) and nonribosomal
      polypeptide synthetase (NRPS) modules direct the biosynthesis of clinically
      valuable natural products in bacteria. The fidelity of this process depends on
      specific recognition between successive polypeptides in each assembly line
      interactions that are mediated by terminal 'docking domains'. We have identified
      a new family of N-terminal docking domains, exemplified by TubCdd from the
      tubulysin system of Angiococcus disciformis An d48. TubCdd is homodimeric, which
      suggests that NRPS subunits in mixed systems self-associate to interact with
      partner PKS homodimers. The NMR structure of TubCdd reveals a new fold featuring
      an exposed beta-hairpin that serves as the binding site for the C-terminal
      docking domain of the partner polypeptide. The pattern of charged residues on the
      contact surface of the beta-hairpin is a key determinant of the interaction and
      seems to constitute a 'docking code' that can be used to alter binding affinity.

PMID- 18066055
TI  - Integrating high-content screening and ligand-target prediction to identify
      mechanism of action.
AB  - High-content screening is transforming drug discovery by enabling simultaneous
      measurement of multiple features of cellular phenotype that are relevant to
      therapeutic and toxic activities of compounds. High-content screening studies
      typically generate immense datasets of image-based phenotypic information, and
      how best to mine relevant phenotypic data is an unsolved challenge. Here, we
      introduce factor analysis as a data-driven tool for defining cell phenotypes and
      profiling compound activities. This method allows a large data reduction while
      retaining relevant information, and the data-derived factors used to quantify
      phenotype have discernable biological meaning. We used factor analysis of cells
      stained with fluorescent markers of cell cycle state to profile a compound
      library and cluster the hits into seven phenotypic categories. We then compared
      phenotypic profiles, chemical similarity and predicted protein binding activities
      of active compounds. By integrating these different descriptors of measured and
      potential biological activity, we can effectively draw mechanism-of-action
      inferences.

PMID- 18066056
TI  - A versatile prion replication assay in organotypic brain slices.
AB  - Methods enabling prion replication ex vivo are important for advancing prion
      studies. However, few such technologies exist, and many prion strains are not
      amenable to them. Here we describe a prion organotypic slice culture assay
      (POSCA) that allows prion amplification and titration ex vivo under conditions
      that closely resemble intracerebral infection. Thirty-five days after contact
      with prions, mouse cerebellar slices had amplified the abnormal isoform of prion
      protein, PrP(Sc), >10(5)-fold. This is quantitatively similar to amplification in
      vivo, but fivefold faster. PrP(Sc) accumulated predominantly in the molecular
      layer, as in infected mice. The POSCA detected replication of prion strains from
      disparate sources, including bovines and ovines, with variable detection
      efficiency. Pharmacogenetic ablation of microglia from POSCA slices led to a 15
      fold increase in prion titers and PrP(Sc) concentrations over those in microglia
      containing slices, as well as an increase in susceptibility to infection. This
      suggests that the extensive microglial activation accompanying prion diseases
      represents an efficacious defensive reaction.

PMID- 18066057
TI  - Prefrontal cortex and basal ganglia control access to working memory.
AB  - Our capacity to store information in working memory might be determined by the
      degree to which only relevant information is remembered. The question remains as
      to how this selection of relevant items to be remembered is accomplished. Here we
      show that activity in the prefrontal cortex and basal ganglia preceded the
      filtering of irrelevant information and that activity, particularly in the globus
      pallidus, predicted the extent to which only relevant information is stored. The
      preceding frontal and basal ganglia activity were also associated with inter
      individual differences in working memory capacity. These findings reveal a
      mechanism by which frontal and basal ganglia activity exerts attentional control
      over access to working memory storage in the parietal cortex in humans, and makes
      an important contribution to inter-individual differences in working memory
      capacity.

PMID- 18066058
TI  - Netrin signal transduction and the guanine nucleotide exchange factor DOCK180 in
      attractive signaling.
AB  - Netrins are prototypical axon guidance cues whose attractive signaling requires
      the small GTPase Rac1. It remains unclear how Rac1 is regulated in the netrin
      pathway. DOCK180 is a member of a new family of guanine nucleotide exchange
      factors for Rho GTPases. Here we provide evidence implicating DOCK180 in netrin
      signal transduction. Netrin promoted the formation of a protein-protein
      interaction complex that included DOCK180 and the netrin receptor deleted in
      colorectal carcinoma (DCC). Inhibition of DOCK180 reduced activation of Rac1 by
      netrin. Both axon outgrowth and axon attraction induced by netrin were inhibited
      after DOCK180 knockdown in vertebrate neurons. The in vivo functional role of
      DOCK180 was demonstrated by its requirement for projection of commissural axons
      in the neural tube. These findings indicate that netrin stimulation recruits
      DOCK180 through DCC, which then activates small GTPases, suggesting an essential
      role for DOCK180 in mediating attractive responses by neurons to netrin-1.

PMID- 18066059
TI  - GTP-independent rapid and slow endocytosis at a central synapse.
AB  - Vesicle endocytosis is essential for maintaining synaptic transmission. Its key
      step, membrane scission, is thought to be mediated by the GTPase dynamin in all
      forms of endocytosis at synapses. Our findings indicate that GTP-independent and
      probably dynamin-independent endocytosis co-exist with GTP- and dynamin-dependent
      endocytosis at the same synaptic nerve terminal, the calyx of Held, in rats. This
      previously undescribed form of endocytosis could be slow (tens of seconds) and/or
      rapid (a few seconds), similar to GTP- and dynamin-dependent endocytosis. It was
      activated during intense stimulation, whereas GTP- and dynamin-dependent
      endocytosis dominated during mild stimulation. These results establish a new
      model, in which vesicles are divided into two pools depending on their
      requirement for GTP and dynamin for retrieval. The GTP- and dynamin-dependent
      pool has higher priority for release and retrieval, but limited capacity,
      saturation of which leads to release and thus retrieval of GTP- and dynamin
      independent vesicles.

PMID- 18066060
TI  - The representation of economic value in the orbitofrontal cortex is invariant for
      changes of menu.
AB  - Economic choice entails assigning values to the available options and is impaired
      by lesions to the orbitofrontal cortex (OFC). Recent results show that some
      neurons in the OFC encode the values that monkeys (Macaca mulatta) assign to
      different goods when they choose between them. A broad and fundamental question
      is how this neuronal representation of value depends on the behavioral context.
      Here we show that neuronal responses in the OFC are typically invariant for
      changes of menu. In other words, the activity of a neuron in response to one
      particular good usually does not depend on what other goods are available at the
      same time. Neurons in the OFC encode economic value, not relative preference. The
      fact that their responses are menu invariant suggests that transitivity, a
      fundamental trait of economic choice, may be rooted in the activity of individual
      neurons.

PMID- 18066061
TI  - A glial amino-acid transporter controls synapse strength and courtship in
      Drosophila.
AB  - Mate choice is an evolutionarily critical decision that requires the detection of
      multiple sex-specific signals followed by central integration of these signals to
      direct appropriate behavior. The mechanisms controlling mate choice remain poorly
      understood. Here, we show that the glial amino-acid transporter genderblind
      controls whether Drosophila melanogaster males will attempt to mate with other
      males. Genderblind (gb) mutant males showed no alteration in heterosexual
      courtship or copulation, but were attracted to normally unappealing male species
      specific chemosensory cues. As a result, genderblind mutant males courted and
      attempted to copulate with other Drosophila males. This homosexual behavior could
      be induced within hours using inducible RNAi, suggesting that genderblind
      controls nervous system function rather than its development. Consistent with
      this, and indicating that glial genderblind regulates ambient extracellular
      glutamate to suppress glutamatergic synapse strength in vivo, homosexual behavior
      could be turned on and off by altering glutamatergic transmission
      pharmacologically and/or genetically.

PMID- 18066062
TI  - Ciliary proteins link basal body polarization to planar cell polarity regulation.
AB  - Planar cell polarity (PCP) refers to coordinated polarization of cells within the
      plane of a cell sheet. A conserved signaling pathway is required for the
      establishment of PCP in epithelial tissues and for polarized cellular
      rearrangements known as convergent extension. During PCP signaling, core PCP
      proteins are sorted asymmetrically along the polarization axis; this sorting is
      thought to direct coordinated downstream morphogenetic changes across the entire
      tissue. Here, we show that a gene encoding a ciliary protein (a 'ciliary gene'),
      Ift88, also known as Polaris, is required for establishing epithelial PCP and for
      convergent extension of the cochlear duct of Mus musculus. We also show that the
      proper positioning of ciliary basal bodies and the formation of polarized
      cellular structures are disrupted in mice with mutant ciliary proteins ('ciliary
      mutants'), whereas core PCP proteins are partitioned normally along the
      polarization axis. Thus, our data uncover a distinct requirement for ciliary
      genes in basal body positioning and morphological polarization during PCP
      regulation.

PMID- 18066063
TI  - Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers
      with deficient DSB repair.
AB  - Basal-like breast cancer (BBC) is a subtype of breast cancer with poor prognosis.
      Inherited mutations of BRCA1, a cancer susceptibility gene involved in double
      strand DNA break (DSB) repair, lead to breast cancers that are nearly always of
      the BBC subtype; however, the precise molecular lesions and oncogenic
      consequences of BRCA1 dysfunction are poorly understood. Here we show that
      heterozygous inactivation of the tumor suppressor gene Pten leads to the
      formation of basal-like mammary tumors in mice, and that loss of PTEN expression
      is significantly associated with the BBC subtype in human sporadic and BRCA1
      associated hereditary breast cancers. In addition, we identify frequent gross
      PTEN mutations, involving intragenic chromosome breaks, inversions, deletions and
      micro copy number aberrations, specifically in BRCA1-deficient tumors. These data
      provide an example of a specific and recurrent oncogenic consequence of BRCA1
      dependent dysfunction in DNA repair and provide insight into the pathogenesis of
      BBC with therapeutic implications. These findings also argue that obtaining an
      accurate census of genes mutated in cancer will require a systematic examination
      for gross gene rearrangements, particularly in tumors with deficient DSB repair.

PMID- 18066064
TI  - AID is required for germinal center-derived lymphomagenesis.
AB  - Most human B cell non-Hodgkin's lymphomas (B-NHLs) derive from germinal centers
      (GCs), the structure in which B cells undergo somatic hypermutation (SHM) and
      class switch recombination (CSR) before being selected for high-affinity antibody
      production. The pathogenesis of B-NHL is associated with distinct genetic
      lesions, including chromosomal translocations and aberrant SHM, which arise from
      mistakes occurring during CSR and SHM. A direct link between these DNA remodeling
      events and GC lymphoma development, however, has not been demonstrated. Here we
      have crossed three mouse models of B cell lymphoma driven by oncogenes (Myc, Bcl6
      and Myc/Bcl6; refs. 5,6) with mice lacking activation-induced cytidine deaminase
      (AID), the enzyme required for both CSR and SHM. We show that AID deficiency
      prevents Bcl6-dependent, GC-derived B-NHL, but has no impact on Myc-driven, pre
      GC lymphomas. Accordingly, abrogation of AID is associated with the disappearance
      of CSR- and SHM-mediated structural alterations. These results show that AID is
      required for GC-derived lymphomagenesis, supporting the notion that errors in AID
      mediated antigen-receptor gene modification processes are principal contributors
      to the pathogenesis of human B-NHL.

PMID- 18066065
TI  - Widespread microRNA repression by Myc contributes to tumorigenesis.
AB  - The c-Myc oncogenic transcription factor (Myc) is pathologically activated in
      many human malignancies. Myc is known to directly upregulate a pro-tumorigenic
      group of microRNAs (miRNAs) known as the miR-17-92 cluster. Through the analysis
      of human and mouse models of B cell lymphoma, we show here that Myc regulates a
      much broader set of miRNAs than previously anticipated. Unexpectedly, the
      predominant consequence of activation of Myc is widespread repression of miRNA
      expression. Chromatin immunoprecipitation reveals that much of this repression is
      likely to be a direct result of Myc binding to miRNA promoters. We further show
      that enforced expression of repressed miRNAs diminishes the tumorigenic potential
      of lymphoma cells. These results demonstrate that extensive reprogramming of the
      miRNA transcriptome by Myc contributes to tumorigenesis.

PMID- 18066066
TI  - Unique functions of the type II interleukin 4 receptor identified in mice lacking
      the interleukin 13 receptor alpha1 chain.
AB  - The interleukin 4 receptor (IL-4R) is a central mediator of T helper type 2
      (T(H)2)-mediated disease and associates with either the common gamma-chain to
      form the type I IL-4R or with the IL-13R alpha1 chain (IL-13Ralpha1) to form the
      type II IL-4R. Here we used Il13ra1-/- mice to characterize the distinct
      functions of type I and type II IL-4 receptors in vivo. In contrast to Il4ra-/-
      mice, which have weak T(H)2 responses, Il13ra1-/- mice had exacerbated T(H)2
      responses. Il13ra1-/- mice showed much less mortality after infection with
      Schistosoma mansoni and much more susceptibility to Nippostrongylus brasiliensis.
      IL-13Ralpha1 was essential for allergen-induced airway hyperreactivity and mucus
      hypersecretion but not for fibroblast or alternative macrophage activation. Thus,
      type I and II IL-4 receptors exert distinct effects on immune responses.

PMID- 18066068
TI  - Atomic-scale study of electric dipoles near charged and uncharged domain walls in
      ferroelectric films.
AB  - Ferroelectrics are materials exhibiting spontaneous electric polarization due to
      dipoles formed by displacements of charged ions inside the crystal unit cell.
      Their exceptional properties are exploited in a variety of microelectronic
      applications. As ferroelectricity is strongly influenced by surfaces, interfaces
      and domain boundaries, there is great interest in exploring how the local atomic
      structure affects the electric properties. Here, using the negative spherical
      aberration imaging technique in an aberration-corrected transmission electron
      microscope, we investigate the cation-oxygen dipoles near 180 degrees domain
      walls in epitaxial PbZr(0.2)Ti(0.8)O(3) thin films on the atomic scale. The width
      and dipole distortion across a transversal wall and a longitudinal wall are
      measured, and on this basis the local polarization is calculated. For the first
      time, a large difference in atomic details between charged and uncharged domain
      walls is reported.

PMID- 18066067
TI  - Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent
      gene expression in drosophila and mice.
AB  - During a genome-wide screen with RNA-mediated interference, we isolated CG8580 as
      a gene involved in the innate immune response of Drosophila melanogaster. CG8580,
      which we called Akirin, encoded a protein that acted in parallel with the NF
      kappaB transcription factor downstream of the Imd pathway and was required for
      defense against Gram-negative bacteria. Akirin is highly conserved, and the human
      genome contains two homologs, one of which was able to rescue the loss-of
      function phenotype in drosophila cells. Akirins were strictly localized to the
      nucleus. Knockout of both Akirin homologs in mice showed that one had an
      essential function downstream of the Toll-like receptor, tumor necrosis factor
      and interleukin (IL)-1beta signaling pathways leading to the production of IL-6.
      Thus, Akirin is a conserved nuclear factor required for innate immune responses.

PMID- 18066069
TI  - Parallel cylindrical water nanochannels in Nafion fuel-cell membranes.
AB  - The structure of the Nafion ionomer used in proton-exchange membranes of
      H(2)/O(2) fuel cells has long been contentious. Using a recently introduced
      algorithm, we have quantitatively simulated previously published small-angle
      scattering data of hydrated Nafion. The characteristic 'ionomer peak' arises from
      long parallel but otherwise randomly packed water channels surrounded by
      partially hydrophilic side branches, forming inverted-micelle cylinders. At 20
      vol% water, the water channels have diameters of between 1.8 and 3.5 nm, with an
      average of 2.4 nm. Nafion crystallites (approximately 10 vol%), which form
      physical crosslinks that are crucial for the mechanical properties of Nafion
      films, are elongated and parallel to the water channels, with cross-sections of
      approximately (5 nm)(2). Simulations for various other models of Nafion,
      including Gierke's cluster and the polymer-bundle model, do not match the
      scattering data. The new model can explain important features of Nafion,
      including fast diffusion of water and protons through Nafion and its persistence
      at low temperatures.

PMID- 18066070
TI  - Cell and biomolecular mechanics in silico.
AB  - Recent developments in computational cell and biomolecular mechanics have
      provided valuable insights into the mechanical properties of cells, subcellular
      components and biomolecules, while simultaneously complementing new experimental
      techniques used for deciphering the structure-function paradigm in living cells.
      These computational approaches have direct implications in understanding the
      state of human health and the progress of disease and can therefore aid immensely
      in the diagnosis and treatment of diseases. We provide an overview of the
      computational approaches that are currently used in understanding various aspects
      of cell and bimolecular mechanics. Our emphasis is on state-of-the-art techniques
      and the progress made in addressing key challenges in biomechanics.

PMID- 18066071
TI  - In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence
      tomography.
AB  - We report a technique for fluorescence tomography that operates beyond the
      penetration limits of tissue-sectioning fluorescence microscopy. The method uses
      multi-projection illumination and photon transport description in opaque tissues.
      We demonstrate whole-body three-dimensional visualization of the morphogenesis of
      GFP-expressing salivary glands and wing imaginal discs in living Drosophila
      melanogaster pupae in vivo and over time.

PMID- 18066072
TI  - Bottom-up genome assembly using the Bacillus subtilis genome vector.
AB  - We established a protocol to construct complete recombinant genomes from their
      small contiguous DNA pieces and obtained the genomes of mouse mitochondrion and
      rice chloroplast using a B. subtilis genome (BGM) vector. This method allows the
      design of any recombinant genomes, valuable not only for fundamental research in
      systems biology and synthetic biology but also for various applications in the
      life sciences.

PMID- 18066073
TI  - Targeted pre-mRNA modification for gene silencing and regulation.
AB  - Most eukaryotic box C/D small nucleolar (sno) or Cajal body-specific RNAs guide
      base pairing with target RNAs and direct site-specific 2'-O-methylation. We
      designed an artificial C/D RNA to target the branch point adenosine of ACT1 pre
      mRNA to block its splicing. Saccharomyces cerevisiae expressing this guide RNA
      gene controlled by a GAL1 promoter grew normally on dextrose but not on galactose
      medium. The pre-mRNA was specifically 2'-O-methylated, prohibiting maturation of
      ACT1 mRNA. Targeting other adenosines in this region while maintaining almost
      identical complementarity did not affect ACT1 mRNA level or cell growth,
      suggesting that targeting the branch-point adenosine was truly 2'-O-methylation
      specific rather than an antisense effect; moreover, only the 3'-most branch site
      adenosine served as the branch point. We targeted other essential intron
      containing genes, and observed a similar phenotype. We demonstrated that a Box
      C/D RNA can guide modification at the pre-mRNA branch point, thus silencing its
      expression and inducing cell death.

PMID- 18066074
TI  - Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+
      regulatory T lymphocytes.
AB  - A major challenge in transplantation medicine is controlling the very strong
      immune responses to foreign antigens that are responsible for graft rejection.
      Although immunosuppressive drugs efficiently inhibit acute graft rejection, a
      substantial proportion of patients suffer chronic rejection that ultimately leads
      to functional loss of the graft. Induction of immunological tolerance to
      transplants would avoid rejection and the need for lifelong treatment with
      immunosuppressive drugs. Tolerance to self-antigens is ensured naturally by
      several mechanisms; one major mechanism depends on the activity of regulatory T
      lymphocytes. Here we show that in mice treated with clinically acceptable levels
      of irradiation, regulatory CD4+CD25+Foxp3+ T cells stimulated in vitro with
      alloantigens induced long-term tolerance to bone marrow and subsequent skin and
      cardiac allografts. Regulatory T cells specific for directly presented donor
      antigens prevented only acute rejection, despite hematopoietic chimerism. By
      contrast, regulatory T cells specific for both directly and indirectly presented
      alloantigens prevented both acute and chronic rejection. Our findings demonstrate
      the potential of appropriately stimulated regulatory T cells for future cell
      based therapeutic approaches to induce lifelong immunological tolerance to
      allogeneic transplants.

PMID- 18066075
TI  - The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury
      by mediating fibroblast recruitment and vascular leak.
AB  - Aberrant wound-healing responses to injury have been implicated in the
      development of pulmonary fibrosis, but the mediators directing these pathologic
      responses have yet to be fully identified. We show that lysophosphatidic acid
      levels increase in bronchoalveolar lavage fluid following lung injury in the
      bleomycin model of pulmonary fibrosis, and that mice lacking one of its
      receptors, LPA1, are markedly protected from fibrosis and mortality in this
      model. The absence of LPA1 led to reduced fibroblast recruitment and vascular
      leak, two responses that may be excessive when injury leads to fibrosis rather
      than to repair, whereas leukocyte recruitment was preserved during the first week
      after injury. In persons with idiopathic pulmonary fibrosis, lysophosphatidic
      acid levels in bronchoalveolar lavage fluid were also increased, and inhibition
      of LPA1 markedly reduced fibroblast responses to the chemotactic activity of this
      fluid. LPA1 therefore represents a new therapeutic target for diseases in which
      aberrant responses to injury contribute to fibrosis, such as idiopathic pulmonary
      fibrosis.

PMID- 18066076
TI  - Purging metastases in lymphoid organs using a combination of antigen-nonspecific
      adoptive T cell therapy, oncolytic virotherapy and immunotherapy.
AB  - In many common cancers, dissemination of secondary tumors via the lymph nodes
      poses the most significant threat to the affected individual. Metastatic cells
      often reach the lymph nodes by mimicking the molecular mechanisms used by
      hematopoietic cells to traffic to peripheral lymphoid organs. Therefore, we
      exploited naive T cell trafficking in order to chaperone an oncolytic virus to
      lymphoid organs harboring metastatic cells. Metastatic burden was initially
      reduced by viral oncolysis and was then eradicated, as tumor cell killing in the
      lymph node and spleen generated protective antitumor immunity. Lymph node purging
      of tumor cells was possible even in virus-immune mice. Adoptive transfer of
      normal T cells loaded with oncolytic virus into individuals with cancer would be
      technically easy to implement both to reduce the distribution of metastases and
      to vaccinate the affected individual in situ against micrometastatic disease. As
      such, this adoptive transfer could have a great therapeutic impact, in the
      adjuvant setting, on many different cancer types.

PMID- 18066077
TI  - Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic
      ubiquitin ligase.
AB  - Bacterial pathogens deliver virulence proteins into host cells to facilitate
      entry and survival. Salmonella SopA functions as an E3 ligase to manipulate the
      host proinflammatory response. Here we report the crystal structure of SopA in
      two conformations. Although it has little sequence similarity to eukaryotic HECT
      domain E3s, the C-terminal half of SopA has a bilobal architecture that is
      reminiscent of the N- and C-lobe arrangement of HECT domains. The SopA structure
      also contains a putative substrate-binding domain located near the E2-binding
      site. The two structures of SopA differ in the relative orientations of the C
      lobe, indicating that SopA possesses the conformational flexibility essential for
      HECT E3 function. These results suggest that SopA is a unique HECT E3 ligase
      evolved from the coevolutionary selective pressure at the bacterium-host
      interface.

PMID- 18066078
TI  - Pot1 and cell cycle progression cooperate in telomere length regulation.
AB  - Removal of the vertebrate telomere protein Pot1 results in a DNA damage response
      and cell cycle arrest. Here we show that loss of chicken Pot1 causes Chk1
      activation, and inhibition of Chk1 signaling prevents the cell cycle arrest.
      However, arrest still occurs after disruption of ATM, which encodes another DNA
      damage response protein. These results indicate that Pot1 is required to prevent
      a telomere checkpoint mediated by another such protein, ATR, that is most likely
      triggered by the G-overhang. We also show that removal of Pot1 causes
      exceptionally rapid telomere growth upon arrest in late S/G2 of the cell cycle.
      However, release of the arrest slows both telomere growth and G-overhang
      elongation. Thus, Pot1 seems to regulate telomere length and G-overhang
      processing both through direct interaction with the telomere and by preventing a
      late S/G2 delay in the cell cycle. Our results reveal that cell cycle progression
      is an important component of telomere length regulation.

PMID- 18066079
TI  - NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate
      its RNA helicase activity.
AB  - Nonsense-mediated mRNA decay (NMD) eliminates mRNAs containing a premature
      translation termination codon through the recruitment of the conserved NMD
      factors UPF1, UPF2 and UPF3. In humans, a dynamic assembly pathway allows UPF1 to
      join UPF2 and UPF3 recruited to the mRNA by the exon-junction complex (EJC). Here
      we show that the recombinant EJC core is sufficient to reconstitute, with the
      three UPF proteins, a stable heptameric complex on RNA. The EJC proteins MAGOH,
      Y14 and eIF4AIII provide a composite binding site for UPF3b that serves as a
      bridge to UPF2 and UPF1. In the UPF trimeric complex, UPF2 and UPF3b
      cooperatively stimulate both ATPase and RNA helicase activities of UPF1. This
      work demonstrates that the EJC core is sufficient to stably anchor the UPF
      proteins to mRNA and provides insights into the regulation of its central
      effector, UPF1.

PMID- 18066080
TI  - Structural basis for the coevolution of a viral RNA-protein complex.
AB  - The cocrystal structure of the PP7 bacteriophage coat protein in complex with its
      translational operator identifies a distinct mode of sequence-specific RNA
      recognition when compared to the well-characterized MS2 coat protein-RNA complex.
      The structure reveals the molecular basis of the PP7 coat protein's ability to
      selectively bind its cognate RNA, and it demonstrates that the conserved beta
      sheet surface is a flexible architecture that can evolve to recognize diverse RNA
      hairpins.

PMID- 18066081
TI  - Structural and functional studies of ALIX interactions with YPX(n)L late domains
      of HIV-1 and EIAV.
AB  - Retrovirus budding requires short peptide motifs (late domains) located within
      the viral Gag protein that function by recruiting cellular factors. The YPX(n)L
      late domains of HIV and other lentiviruses recruit the protein ALIX (also known
      as AIP1), which also functions in vesicle formation at the multivesicular body
      and in the abscission stage of cytokinesis. Here, we report the crystal
      structures of ALIX in complex with the YPX(n)L late domains from HIV-1 and EIAV.
      The two distinct late domains bind at the same site on the ALIX V domain but
      adopt different conformations that allow them to make equivalent contacts.
      Binding studies and functional assays verified the importance of key interface
      residues and revealed that binding affinities are tuned by context-dependent
      effects. These results reveal how YPX(n)L late domains recruit ALIX to facilitate
      virus budding and how ALIX can bind YPX(n)L sequences with both n = 1 and n = 3.

PMID- 18066083
TI  - DNA double-strand breaks: their cellular and clinical impact?

PMID- 18066084
TI  - BRCA2: a universal recombinase regulator.
AB  - Homologous recombination has a dual role in eukaryotic organisms. Firstly, it is
      responsible for the creation of genetic variability during meiosis by directing
      the formation of reciprocal crossovers that result in random combinations of
      alleles and traits. Secondly, in mitotic cells, it maintains the integrity of the
      genome by promoting the faithful repair of DNA double-strand breaks (DSBs). In
      vertebrates, it therefore plays a key role in tumour avoidance. Mutations in the
      tumour suppressor protein BRCA2 are associated with predisposition to breast and
      ovarian cancers, and loss of BRCA2 function leads to genetic instability. BRCA2
      protein interacts directly with the RAD51 recombinase and regulates recombination
      mediated DSB repair, accounting for the high levels of spontaneous chromosomal
      aberrations seen in BRCA2-defective cells. Recent observations indicate that
      BRCA2 also plays a critical role in meiotic recombination, this time through
      direct interactions with the meiosis-specific recombinase DMC1. The interactions
      of BRCA2 with RAD51 and DMC1 lead us to suggest that the BRCA2 tumour suppressor
      is a universal regulator of recombinase actions.

PMID- 18066085
TI  - Non-homologous end-joining, a sticky affair.
AB  - Rejoining of broken chromosomes is crucial for cell survival and prevention of
      malignant transformation. Most mammalian cells rely primarily on the non
      homologous end-joining pathway of DNA double-strand break (DSB) repair to
      accomplish this task. This review focuses both on the core non-homologous end
      joining machinery, which consists of DNA-dependent protein kinase and the ligase
      IV/XRCC4 complex, and on accessory factors that facilitate rejoining of a subset
      of the DSBs. We discuss how the ATM protein kinase and the Mre11/Rad50/Nbs1
      complex might function in DSB repair and what role ionizing radiation-induced
      foci may play in this process.

PMID- 18066086
TI  - Activation and regulation of ATM kinase activity in response to DNA double-strand
      breaks.
AB  - The ataxia-telangiectasia-mutated (ATM) protein kinase is rapidly and
      specifically activated in response to DNA double-strand breaks in eukaryotic
      cells. In this review, we summarize recent insights into the mechanism of ATM
      activation, focusing on the role of the Mre11/Rad50/Nbs1 (MRN) complex in this
      process. We also compare observations of the ATM activation process in different
      biological systems and highlight potential candidates for cellular factors that
      may participate in regulating ATM activity in human cells.

PMID- 18066087
TI  - ATM and the Mre11 complex combine to recognize and signal DNA double-strand
      breaks.
AB  - The recognition and repair of DNA double-strand breaks (DSBs) is a complex
      process that draws upon a multitude of proteins. This is not surprising since
      this is a lethal lesion if left unrepaired and also contributes to genome
      instability and the consequential risk of cancer and other pathologies. Some of
      the key proteins that recognize these breaks in DNA are mutated in distinct
      genetic disorders that predispose to agent sensitivity, genome instability,
      cancer predisposition and/or neurodegeneration. These include members of the
      Mre11 complex (Mre11/Rad50/Nbs1) and ataxia-telangiectasia (A-T) mutated (ATM),
      mutated in the human genetic disorder A-T. The mre11 (MRN) complex appears to be
      the major sensor of the breaks and subsequently recruits ATM where it is
      activated to phosphorylate in turn members of that complex and a variety of other
      proteins involved in cell-cycle control and DNA repair. The MRN complex is also
      upstream of ATM and ATR (A-T-mutated and rad3-related) protein in responding to
      agents that block DNA replication. To date, more than 30 ATM-dependent substrates
      have been identified in multiple pathways that maintain genome stability and
      reduce the risk of disease. We focus here on the relationship between ATM and the
      MRN complex in recognizing and responding to DNA DSBs.

PMID- 18066088
TI  - Breaking down cell cycle checkpoints and DNA repair during antigen receptor gene
      assembly.
AB  - Double-strand breaks (DSBs) are intermediates in several physiological processes
      including V(D)J and class switch recombination. They are also potent substrates
      for chromosomal translocations that arise as by-products of antigen receptor gene
      assembly in lymphocytes. ATM is one among several key proteins involved in the
      detection, signaling and repair of DNA breaks. Despite redundancies in DSB
      signaling pathways, it has recently been demonstrated that ATM deficient
      lymphocytes can survive and proliferate several generations in vitro and in vivo
      despite harboring terminally deleted chromosomes produced by V(D)J recombination.
      In this review, we discuss how two complementary genome maintenance functions
      mediated by ATM prevent lymphocytes from adapting to persistent DNA damage.

PMID- 18066089
TI  - Chromatin structure and DNA double-strand break responses in cancer progression
      and therapy.
AB  - Defects in the detection and repair of DNA double-strand breaks (DSBs) have been
      causatively linked to tumourigenesis. Moreover, inhibition of DNA damage
      responses (DDR) can increase the efficacy of cancer therapies that rely on
      generation of damaged DNA. DDR must occur within the context of chromatin, and
      there have been significant advances in recent years in understanding how the
      modulation and manipulation of chromatin contribute to this activity. One
      particular covalent modification of a histone variant--the phosphorylation of
      H2AX--has been investigated in great detail and has been shown to have important
      roles in DNA DSB responses and in preventing tumourigenesis. These studies are
      reviewed here in the context of their relevance to cancer therapy and
      diagnostics. In addition, there is emerging evidence for contributions by
      proteins involved in mediating higher order structure to DNA DSB responses. The
      contributions of a subset of these proteins--linker histones and high-mobility
      group box (HMGB) proteins--to DDR and their potential significance in
      tumourigenesis are discussed.

PMID- 18066090
TI  - DNA damage signalling guards against activated oncogenes and tumour progression.
AB  - DNA damage response (DDR), the guardian of genomic integrity, emerges as an
      oncogene-inducible biological barrier against progression of cancer beyond its
      early stages. Recent evidence from both cell culture and animal models as well as
      analyses of clinical specimens show that activation of numerous oncogenes and
      loss of some tumour suppressors result in DNA replication stress and DNA damage
      that alarm the cellular DDR machinery, a multifaceted response orchestrated by
      the ATR-Chk1 and ATM-Chk2 kinase signalling pathways. Such activation of the DDR
      network leads to cellular senescence or death of oncogene-transformed cells,
      resulting in delay or prevention of tumorigenesis. At the same time, the ongoing
      chronic DDR activation creates selective pressure that eventually favours
      outgrowth of malignant clones with genetic or epigenetic defects in the genome
      maintenance machinery, such as aberrations in the ATM-Chk2-p53 cascade and other
      DDR components. Furthermore, the executive DDR machinery is shared by at least
      two anticancer barriers, as both the oncogene-induced DNA replication stress and
      telomere shortening impact the cell fate decisions through convergence on DNA
      damage signalling. In this study, we highlight recent advances in this rapidly
      evolving area of cancer research, with particular emphasis on mechanistic
      insights, emerging issues of special conceptual significance and discussion of
      major remaining challenges and implications of the concept of DDR as a
      tumorigenesis barrier for experimental and clinical oncology.

PMID- 18066091
TI  - V(D)J and immunoglobulin class switch recombinations: a paradigm to study the
      regulation of DNA end-joining.
AB  - The immune system is the site of intense DNA damage/modification, which occur
      during the development and maturation of B and T lymphocytes. V(D)J recombination
      is initiated by the Rag1 and Rag2 proteins and the formation of a DNA double
      strand break (DNA dsb). This DNA lesion is repaired through the use of the non
      homologous end-joining (NHEJ) pathway, several factors of which have been
      identified through the survey of immunodeficient conditions in humans and mice.
      Upon antigenic recognition in secondary lymphoid organs, mature B cells further
      diversify their repertoire through class switch recombination (CSR). CSR is a
      region-specific rearrangement process triggered by the activation-induced
      cytidine deaminase factor and also proceeds through the introduction of DNA dsb.
      However, unlike V(D)J recombination, CSR does not rely strictly on NHEJ for the
      repair of the DNA lesion. Instead, CSR, but not V(D)J recombination, requires the
      major factors of the DNA damage response. V(D)J recombination and CSR thus
      represent an interesting paradigm to study the regulation among the various DNA
      repair pathways.

PMID- 18066092
TI  - The clinical manifestation of a defective response to DNA double-strand breaks as
      exemplified by Nijmegen breakage syndrome.
AB  - The autosomal recessive genetic disorder Nijmegen breakage syndrome (NBS) was
      first described in 1981 in patients living in Nijmegen, Holland. NBS patients
      display a characteristic facial appearance, microcephaly and a range of symptoms
      including immunodeficiency, increased cancer risk and growth retardation. In
      addition, NBS patient cells were found to have elevated levels of chromosomal
      damage and to be sensitive to ionizing irradiation (IR). This radiosensitivity
      had fatal consequences in some undiagnosed patients. The most dangerous DNA
      lesion caused by IR is considered to be the double-strand break (DSB) and indeed,
      NBS patient cells are sensitive to all mutagens that produce DSBs directly or
      indirectly. We discuss here our current understanding of how a deficiency in DSB
      repair manifests as the particular symptom complex of NBS.

PMID- 18066093
TI  - DNA double-strand break repair and development.
AB  - Normal development of an organism requires the ability to respond to DNA damage.
      A particularly deleterious lesion is a DNA double-strand break (DSB). The
      cellular response to DNA DSBs occurs via an integrated sensing and signaling
      network that maintains genomic stability. The outcomes of defective DNA DSB
      repair are related to the developmental stage of an organism, and often show
      striking tissue specificity. Many human diseases are associated with deficiencies
      in DNA DSB repair and can be characterized by neuropathology, immune deficiency,
      growth retardation or predisposition to cancer. This review will focus on the
      requirements of the DNA DSB response that function to maintain homeostasis during
      mammalian development.

PMID- 18066094
TI  - Glioblastoma multiforme: the role of DSB repair between genotype and phenotype.
AB  - Glioblastoma is the most frequent primary brain tumor in adults. The average
      survival time of less than 1 year did not improve notably over the last three
      decades. The dismal prognosis of glioblastoma patients is largely due to the
      striking radioresistance of this tumor. Here, we attempt a combined view on the
      genetics, the repair mechanisms and the radioresistance of glioblastoma.
      Specifically, we address the role of DNA-PKcs and the novel potential end-joining
      factor KUB3 in maintaining the radioresistant phenotype, the interrelationship
      between genetic lesions and repair mechanisms, and new perspectives that emerge
      from the identification of glioblastoma stem cells.

PMID- 18066095
TI  - Targeted cancer therapies based on the inhibition of DNA strand break repair.
AB  - Both DNA double- and single-strand break repair are highly coordinated processes
      utilizing signal transduction cascades and post-translational modifications such
      as phosphorylation, acetylation and ADP ribosylation. 'Drugable' targets within
      these networks have been identified that could potentially lead to novel
      therapeutic approaches within the oncology arena. Key regulators within these
      signalling cascades, such as DNA-dependent protein kinase, ataxia-telangiectasia
      mutated, checkpoint kinase 1 (CHK1), checkpoint kinase 2 (CHK2) and poly(ADP
      ribose) polymerase, use either ATP or nicotinamide adenine dinucleotide for their
      enzymatic functions and are therefore readily accessible to small molecule
      inhibition at their catalytic sites. A range of highly potent and selective
      inhibitors of these DNA damage response pathways has now been identified through
      drug discovery efforts, with candidate molecules either approaching or already in
      clinical trials. This review will describe the small molecule inhibitors and drug
      discovery activities that focus on DNA break repair, along with the therapeutic
      rationale behind chemosensitization and the concept of synthetic lethality. We
      will also describe the emerging clinical data coming from this exciting new
      approach to targeted cancer therapy.

PMID- 18066097
TI  - REACH: Innovative legislation to reduce chemical exposures.

PMID- 18066098
TI  - Novel bisindolylmaleimide derivative inhibits mitochondrial permeability
      transition pore and protects the heart from reperfusion injury.
AB  - Despite major advances in treating patients with coronary heart disease,
      reperfusion injury is still considered to be a major problem, especially in
      surgical settings. Here, we demonstrate the protective effects of a novel
      bisindolylmaleimide derivative, MS1 (2-[1-(3-aminopropyl)indol-3-yl]-3-(indol-3
      yl)-N-methylmaleimide), against reperfusion injury of the heart. After anesthesia
      and artificial ventilation, Wistar rats were subjected to 30 min of left coronary
      artery occlusion followed by 120 min of reperfusion with or without treating the
      rats with MS1 (2.25 mumol.L-1.kg-1) before left coronary artery occlusion.
      Compared with the untreated hearts, MS1 treatment significantly reduced
      myocardial infarct size (35.1% +/- 3% vs. 75.5% +/- 5%, p < 0.001), reduced
      prevalence of apoptotic cells (2.6% +/- 0.5% vs. 12.2% +/- 2.1%, p < 0.001),
      prevented mitochondrial swelling and cytochrome c release, inhibited
      downregulation of antiapoptotic protein Bcl-2 expression, and suppressed caspase
      3 activation. In contrast, pretreatment with atractyloside, a mitochondrial
      permeability transition pore opener, abolished the protective effects of MS1. In
      conclusion, MS1 inhibits pathologic opening of permeability transition pores and
      protects the heart against reperfusion injury and pathologic apoptosis.

PMID- 18066099
TI  - Ubiquinol-cytochrome-c reductase 7.2 kDa protein of mitochondrial complex III is
      steroid-responsive and increases in cardiac hypertrophy and hypertension.
AB  - Women and men do not respond identically to cardiac insults; premenopausal women
      are somewhat protected from cardiovascular disease. Our objective was to isolate
      and characterize hormone-responsive genes in the heart. Differential display
      identified an estrogen-inducible fragment that was found to encode the ubiquinol
      cytochrome-c reductase (UCCR) 7.2 kDa protein of the mitochondrial respiratory
      complex III. We found UCCR7.2 mRNA to be highly expressed in the heart, and this
      expression increased in hearts of 4-, 10-, and 28-week-old spontaneously
      hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats. Oral
      hydralazine treatment to reduce hypertension reduced SHR UCCR7.2 expression.
      Cardiac UCCR7.2 mRNA expression was also increased significantly after a 5/6
      nephrectomy compared with mock surgery. Cardiac expression after ovariectomy was
      50% that of intact rats. Supplementation of ovariectomized rats with estrogen had
      no effect, whereas progesterone increased cardiac expression, although not to
      intact levels. No change in cardiac UCCR7.2 expression was found when intact rats
      were treated with either tamoxifen or ICI 182780. Thus, UCCR7.2 expression is
      reduced in the absence of ovarian hormones, but is not directly regulated by
      estrogen in the heart. We conclude that UCCR7.2 is a steroid hormone-responsive
      gene in the heart, with expression increased in cardiac hypertrophy and in
      response to hypertension.

PMID- 18066100
TI  - Interrelationship of antioxidative status, lipid peroxidation, and lipid profile
      in insulin-dependent and non-insulin-dependent diabetic patients.
AB  - This study aimed to investigate the interrelationship of plasma lipid profile,
      lipid peroxidation, and erythrocyte antioxidative defense in patients with
      insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus.
      Plasma levels of total cholesterol, triglycerides, and lipid peroxides and the
      activities of copper, zinc superoxide dismutase (CuZnSOD), catalase, glutathione
      peroxidase (GSH-Px), as well as the amount of glutathione in erythrocytes, were
      determined in IDDM, NIDDM, and nondiabetic control subjects. Additionally,
      morphology of erythrocytes in all subjects was examined. Plasma levels of total
      cholesterol and triglycerides were significantly increased in NIDDM compared with
      controls. Also, the lipid peroxide level was higher in NIDDM than in either
      control or IDDM subjects. CuZnSOD activity in erythrocytes was elevated in NIDDM
      patients compared with the control. In NIDDM patients, more extensive erythrocyte
      spherocytosis and echinocytosis compared with both control and IDDM subjects were
      observed. In contrast with the IDDM group, the observed abnormality in lipid
      metabolism in NIDDM patients is closely associated with increased lipid
      peroxidation, changes in antioxidative defense, and erythrocyte morphology.

PMID- 18066101
TI  - Older versus newer antidepressants: substance P or calcium antagonism?
AB  - Substance P (SP) is possibly involved in the pathophysiology of depression and
      anxiety. We investigated interactions between antidepressants on SP-induced
      effects and their potential calcium-blocking activity in the isolated guinea pig
      ileum. All the antidepressants tested, except pargyline, moclobemide, mianserin,
      and reboxetine, were able to inhibit in a concentration-dependent manner the
      contraction induced by 100 nmol/L SP. Clomipramine, fluoxetine, maprotiline, and
      amitriptyline (all at 3 mumol/L) flattened the concentration-response curves to
      SP, resulting in a reduction of up to 59%, 63%, 32%, and 23%, respectively, of
      the maximum contractile effect. All the antidepressants tested (3 mumol/L),
      except pargyline, moclobemide, and mianserin, produced a rightward parallel shift
      of the concentration-response curve to CaCl2. The L-type selective calcium
      blocker nifedipine and the T-type selective mibefradil showed similar behaviour
      against both agonists used, SP and CaCl2. The relative order of potency was
      nifedipine (pA2, 7.6 +/- 0.1) > clomipramine (pA2, 7.0 +/- 0.1) > fluoxetine
      (pKB, 6.5 +/- 0.1) = mibefradil (pKB, 6.6 +/- 0.1) > amitriptyline (pKB, 6.3 +/-
      0.1) = maprotiline (pKB, 6.2 +/- 0.1) > fluvoxamine (pKB, 5.9 +/- 0.1). The data
      reported in the present study suggest that the antidepressants tested did not
      behave as competitive antagonists versus NK1-receptor subtypes, but their
      inhibitory action seems to be related to their calcium-blocking properties.

PMID- 18066102
TI  - Salvia miltiorrhiza treatment during early reperfusion reduced postischemic
      myocardial injury in the rat.
AB  - Oxidative stress may play a causative role in myocardial ischemia-reperfusion
      injury. However, it is a relatively understudied aspect regarding an optimal
      timing of antioxidant intervention during ischemia-reperfusion. The present study
      investigates the effect of different treatment regimens of Salvia miltiorrhiza
      (SM) herb extracts containing phenolic compounds that possess potent antioxidant
      properties on postischemic myocardial functional recovery in the setting of
      global myocardial ischemia and reperfusion. Langendorff-perfused rat hearts were
      subjected to 40 min of global ischemia at 37 degrees C followed by 60 min of
      reperfusion, and were randomly assigned into the untreated control and 2 SM
      treated groups (n = 7 per group). In treatment 1 (SM1), 3 mg/mL of water soluble
      extract of SM was given for 10 min before ischemia and continued during ischemia
      through the aorta at a reduced flow rate of 60 microL/min, but not during
      reperfusion. In treatment 2 (SM2), SM (3 mg/mL) was given during the first 15 min
      of reperfusion. During ischemia, hearts in the control and SM2 groups were given
      physiological saline at 60 microL/min. The SM1 treatment reduced the production
      of 15-F2t-isoprostane, a specific index of oxidative stress-induced lipid
      peroxidation, during ischemia (94 +/- 20, 43 +/- 6, and 95 +/- 15 pg/mL in the
      coronary effluent in control, SM1, and SM2 groups, respectively; p < 0.05, SM1
      vs. control or SM2) and postponed the onset of ischemic contracture. However,
      SM2, but not the SM1 regimen, significantly reduced 15-F2t-isoprostane production
      during early reperfusion and led to optimal postischemic myocardial functional
      recovery (left ventricular developed pressure 51 +/- 4, 46 +/- 4, and 60 +/- 6
      mmHg in the control, SM1, and SM2 groups, respectively, at 60 min of reperfusion;
      p < 0.05, SM2 vs. control or SM1) and reduced myocardial infarct size as measured
      by triphenyltetrazolium chloride staining (26% +/- 2%, 22% +/- 2%, and 20% +/- 2%
      of the total area in the control, SM1, and SM2 groups, respectively, p < 0.05,
      SM2 vs. control). It is concluded that S. miltiorrhiza could be beneficial in the
      treatment of myocardial ischemic injury and the timing of administration seems
      important.

PMID- 18066103
TI  - Inhibitory effects of aqueous extract of Hibiscus sabdariffa on contractility of
      the rat bladder and uterus.
AB  - We examined an aqueous extract of Hibiscus sabdariffa calyces extracts (HSE) by
      close-arterial injection on micturition thresholds (MTs) and on uterine
      contractions (rate and amplitude). Five doses of HSE were examined (1, 5, 10, 50,
      and 100 mg/kg) in 3 groups of rats: controls, after bladder inflammation, and
      after bilateral hypogastric neurectomy. In some rats, uterine contractions were
      induced by injection of oxytocin (OT) and the effect of HSE was compared with
      that of nifedipine. HSE increased MTs in a dose-dependent manner in all groups.
      Neither atropine (0.1 mg/kg) nor propranolol (0.4 mg/kg) had significant effects
      on cystometric parameters. They also did not affect the responses obtained by HSE
      on cystometric parameters. As with bladder response, HSE inhibited both the rate
      and amplitude of uterine contractions in all groups in a dose-dependent manner.
      The uterine response to HSE was not affected by administration of either atropine
      or propranolol. A slight, but significant, reduction of contraction amplitude by
      HSE in the OT precontracted uteri was only noted at a dose of 500 mg/kg.
      Nifedipine was more potent than HSE in reducing uterine contraction amplitude.
      The present work documents inhibition by HSE of the rat bladder and uterine
      contractility in a dose-dependent manner via a mechanism unrelated to local or
      remote autonomic receptors or calcium channels. However, further investigation is
      needed to establish the exact mechanism of action.

PMID- 18066104
TI  - Moderate body hypothermia alleviates behavioral and EEG manifestations of
      audiogenic seizures in metaphit-treated rats.
AB  - We investigated the effects of hypothermia on the incidence and EEG signs of
      audiogenic seizures in rats treated with metaphit (1-[1(3isothiocyanatophenyl)
      cyclohexyl] piperidine), an experimental model of generalized reflex epilepsy.
      After i.p. injection with metaphit (10 mg/kg) Wistar rats were exposed to
      audiogenic stimulation at hourly intervals during the time course of the
      experiment. After intermittent use of an ice pack 8 h after the metaphit
      treatment, when seizure was fully developed, the body temperature was reduced to
      30 +/- 0.5 degrees C in one half of the rats, and maintained at 37 +/- 0.5
      degrees C in the other half. Saline-injected rats served as a control group. In
      the hypothermia group, the incidence of audiogenic seizures induced by metaphit
      was completely suppressed during the 3 consecutive testing times, while no signs
      of epileptiform activity were noted in EEG tracings. The termination of
      hypothermic treatment resulted in the recovery of seizure susceptibility, and
      during audiogenic stimulation, bursts of spiking activity were recorded in the
      EEGs of metaphit-treated rats. These findings indicate that moderate body
      hypothermia is an effective anticonvulsant treatment for audiogenic seizures in
      metaphit-treated rats.

PMID- 18066105
TI  - Effect of chronic lithium administration on endothelium-dependent relaxation of
      rat mesenteric bed: role of nitric oxide.
AB  - The mechanism of action of lithium, an effective treatment for bipolar disease,
      is still unknown. In this study, the mesenteric vascular beds of control rats and
      rats that were chronically treated with lithium were prepared by the McGregor
      method, and the mesenteric vascular bed vasorelaxation responses were examined.
      NADPH-diaphorase histochemistry was used to determine the activity of NOS (nitric
      oxide synthase) in mesenteric vascular beds. We demonstrated that ACh-induced
      vasorelaxation increased in the mesenteric vascular bed of rats treated with
      lithium. Acute No-nitro-L-arginine methyl ester (L-NAME) administration in the
      medium blocked ACh-induced vasorelaxation in the control group more effectively
      than in lithium-treated rats, while the vasorelaxant response to sodium
      nitroprusside, a NO donor, was not different between lithium-treated and control
      groups. Acute aminoguanidine administration blocked ACh-induced vasorelaxation of
      lithium-treated rats, but had no effect in the control rats. Furthermore, NOS
      activity, determined by NADPH-diaphorase staining, was significantly greater in
      the mesenteric vascular beds from chronic lithium-treated rats than in those from
      control rats. These data suggest that the enhanced ACh-induced endothelium
      derived vasorelaxation in rat mesenteric bed from chronic lithium-treated rats
      might be associated with increased NOS activity, likely via iNOS. Simultaneous
      acute L-NAME and indomethacin administration suggests the possible upregulation
      of EDHF (endothelium-derived hyperpolarizing factor) in lithium-treated rats.

PMID- 18066106
TI  - Oxidative stress in primary culture hepatocytes isolated from partially
      hepatectomized rats.
AB  - The aim of this study was to evaluate the influence of partial hepatectomy prior
      to cell isolation on hepatocytes in vitro. We characterized the possible changes
      of various stress oxidative parameters within the first 24 h after seeding. Male
      Wistar rats served as donors. Hepatocytes were isolated by collagenase digestion
      from either liver of simulated surgery (SH) or from liver 1 h after 70%
      hepatectomy (PH), and the changes in stress parameters were analyzed after 1, 3,
      18, and 24 h in culture. At 24 h, only hepatocytes from PH maintained
      significantly increased reactive oxygen species production, oxidized glutathione
      percentage, and Cu/Zn superoxide dismutase and catalase activities. Our results
      show that hepatocytes suffer significant cell injury as a result of the isolation
      procedure, but primary cultured cells from SH metabolically recover from this
      stress after 18 h. After this time, primary culture hepatocytes primed by PH
      maintain their in vivo-like metabolic activities (increase in both oxidative
      stress and antioxidant status).

PMID- 18066108
TI  - Senecio latifolius induces in vitro hepatocytotoxicity in a human cell line.
AB  - The objectives of this study were twofold: (i) to determine the mechanism(s) of
      Senecio-induced toxicity in human hepatoblastoma cells (HepG2) in vitro and
      whether such toxicity could be prevented using N-acetyl-cysteine (NAC), and (ii)
      to evaluate whether caspases are involved in Senecio-induced apoptosis. Cells
      were treated with aqueous extracts of Senecio (10 mg x mL-1) with and without
      NAC. Cytotoxicity was determined by using the MTT assay. Total glutathione (GSH)
      was measured by using the Tietze assay. Cells were also treated with aqueous
      extracts of Senecio in the presence or absence of 50 micromol/L caspase-3
      inhibitor (IDN) for 24 h. Apoptosis was determined by transmission electron
      microscopy, and DNA fragmentation was determined by ELISA and terminal dUTP nick
      end labelling (TUNEL). Senecio produced cytotoxicity and depleted GSH in a
      concentration- and time-dependent manner. A significant depletion in GSH was
      observed after 15 min (p < 0.001 vs. control), whereas significant cytotoxicity
      was only observed after 3 h (p < 0.001 vs. control). Treatment with NAC prevented
      Senecio-induced GSH depletion and resulted in a significant decrease in Senecio
      induced cytotoxicity (p < 0.001 vs. NAC-untreated cells). Treatment with Senecio
      for 24 h resulted in 22% +/- 2.5% (p < 0.001) apoptosis (vs. control).
      Pretreatment with 50 mumol caspase inhibitor reduced Senecio-induced apoptosis
      significantly (vs. non-exposed to IDN) (12% +/- 1.5%; p < 0.05). Our results
      suggest the mechanism of Senecio-induced cytotoxicity in HepG2 cells in vitro
      involves depletion of cellular GSH. Cytotoxicity is reduced by supplementation
      with NAC, which thus prevents GSH depletion. Caspase activation is involved in
      Senecio-induced apoptosis.

PMID- 18066107
TI  - Magnesium tanshinoate B protects endothelial cells against oxidized lipoprotein
      induced apoptosis.
AB  - The activation of c-Jun N-terminal kinase (JNK) signaling pathway plays an
      important role in the induction of cell apoptosis. We previously reported that
      magnesium tanshinoate B (MTB), a compound purified from a Chinese herb danshen
      (Salvia miltiorrhiza), could inhibit ischemia/reperfusion-induced myocyte
      apoptosis in the heart. The objective of the present study was to investigate
      whether MTB can prevent oxidized lipoprotein-induced apoptosis in endothelial
      cells. Human umbilical vein endothelial cells (HUVECs) were incubated with copper
      oxidized very low density lipoprotein (Cu-OxVLDL) or copper-oxidized low density
      lipoprotein (Cu-OxLDL). Treatment of cells with Cu-OxVLDL or Cu-OxLDL resulted in
      a 3-fold increase in the JNK activity. The amount of cytochrome c released and
      the activity of caspase-3 in cells treated with Cu-OxVLDL or Cu-OxLDL were
      significantly elevated, indicating the occurrence of apoptosis. The presence of
      MTB was able to abolish the JNK activation, cytochrome c release, and caspase-3
      activation induced by Cu-OxVLDL or Cu-OxLDL, resulting in a marked reduction in
      apoptosis in endothelial cells. The data from this study indicate that oxidized
      lipoproteins induce apoptosis in endothelial cells. We postulate that the
      inhibition of the JNK signaling pathway by MTB is a key mechanism that protects
      these cells from oxidized lipoprotein-induced apoptosis.

PMID- 18066109
TI  - Antidiabetic potential of oleanolic acid from Ligustrum lucidum Ait.
AB  - Ligustrum lucidum Ait. has been used in traditional Chinese medicine for over
      1000 years because of its anti-tumor, antimutagenic, antidiabetic, and
      hepatoprotective properties. The aim of this study was to determine whether
      oleanolic acid (OA) is the principal active compound of L. lucidum responsible
      for its antidiabetic properties, and to examine its effect on the expression of
      thyroid hormones and insulin secretion, thus revealing the mechanism by which L.
      lucidum modulates insulin levels in diabetes. When rats with streptozotocin
      induced diabetes were treated with OA (100 and 200 mg/kg body mass per day, for
      40 days), the changes in blood glucose levels and in oral glucose tolerance tests
      showed that hypoglycemia was more pronounced in OA-treated groups than in the
      diabetic control rats, and that the levels of triglyceride, total cholesterol,
      and low-density lipoportein cholesterol in OA-treated rats were lower than those
      in the diabetic control rats, whose high-density lipoprotein cholesterol
      increased. OA-treated rats also gained weight, and exhibited increased serum
      insulin levels. In contrast, OA treatment did not effect the levels of thyroid
      hormone or TSH in rats with streptozotocin-induced diabetes. These results
      indicate that OA has hypoglycemic and hypolipidemic effects. OA treatment might
      stimulate insulin release, and consequently, results in the modulation of glucose
      levels and regulation of lipid metabolism.

PMID- 18066110
TI  - In vitro evaluation of the antiviral effects of the homeopathic preparation Gripp
      Heel on selected respiratory viruses.
AB  - Gripp-Heel is a homeopathic preparation frequently used in the treatment of
      respiratory viral infections such as various types of influenza and the common
      cold. The antiviral activity of Gripp-Heel was studied in vitro on human
      pathogenic enveloped and nonenveloped RNA and DNA viruses. Before the antiviral
      assays, in vitro cytotoxicity of Gripp-Heel was determined with cells used for
      the infection experiments (HeLa, HEp-2, MDCK, BGM) as well as with mitogen
      stimulated peripheral blood mononuclear leukocytes. A concentration of 0.5 of the
      commercially available product slightly reduced cell viability and proliferative
      capacity, and experiments on antiviral activity were determined starting with a
      dilution of 0.2 of the commercially available product. The antiviral activity was
      determined against a broad panel of enveloped and nonenveloped DNA and RNA
      viruses with plaque reduction assay, cytopathogenic assays, virus titrations,
      analysis of the viral proteins in virus-specific enzyme immunoassays, and
      haemagglutination tests. Control substances were acyclovir (10 microg/mL),
      ribavirin (6 microg/mL), and amantadine hydrochloride (5 microg/mL), depending on
      the virus type. Gripp-Heel demonstrated dose-dependent in vitro activity
      (significant reductions of infectivity by 20% to 40%) against Human herpesvirus
      1, Human adenovirus C serotype 5, Influenza A virus, Human respiratory syncytial
      virus, Human parainfluenza virus 3, Human rhinovirus B serotype 14, and Human
      coxsackievirus serotype A9. The mechanisms of this antiviral activity are still
      unclear, but type I interferon induction might be a possible explanation. Further
      research on this homeopathic preparation seems warranted.

PMID- 18066111
TI  - Modulation of immune response gene expression by echinacea extracts: results of a
      gene array analysis.
AB  - Echinacea extracts have traditionally been used in the treatment of many
      infectious and other diseases (such as rhinovirus colds), and research has
      revealed the presence of various bioactivities in these extracts, particularly
      those connected with immune responses. We examined the effects of Echinacea by
      using gene expression analysis in a line of human bronchial epithelial cells,
      with or without rhinovirus infection. More than 13 000 human genes were
      evaluated. From these analyses we focused primarily on immune response genes and
      found that both Echinacea extracts, one predominantly rich in polysaccharides and
      the other rich in alkylamides and caffeic acid derivatives, stimulated the
      expression of numerous genes. These included a number of cytokines and
      chemokines, although the pattern of stimulation was different. In addition,
      Echinacea extracts tended to neutralize the effects of the rhinovirus. When the
      immune response gene pathways were analyzed with the Ingenuity Pathway program,
      it became apparent that many of them were interconnected through a major node,
      the transcription factor C/EBPbeta (CAAT/enhancer-binding protein beta) and its
      related C/EBP proteins. This suggests that Echinacea can bring about important
      biological responses in cells by virtue of interactions between components of the
      extract and a small number of intracellular factors involved in multiple
      signaling pathways.

PMID- 18066112
TI  - In vitro activity of uva-ursi against cytochrome P450 isoenzymes and P
      glycoprotein.
AB  - Some natural health products (NHPs) affect drug metabolism enzymes and transport
      proteins, potentially affecting the safety and efficacy of the drug or other
      NHPs. This study was undertaken to characterize the effect of uva-ursi
      (Arctostaphylos uva-ursi) on cytochrome P450 isozyme (3A4, 3A5, 3A7, 2C19, and
      19)-mediated metabolism and P-glycoprotein (P-gp) transport. Three bulk and 2
      capsulated uva-ursi samples were obtained from commercial outlets. The capsules
      were batched, and herbal samples were ground to a common consistency. Aqueous and
      methanol extracts were freshly prepared. Cytochrome P450 isozyme-mediated
      metabolism was determined by using in vitro bioassays. P-gp transport function
      was determined by using a rhodamine 123 (Rh123) uptake test in human (THP-1)
      monocytes and human Caco-2 cells. All products were analyzed by HPLC for arbutin,
      gallic acid, myricitrin, and isoquercetin. A large variation was observed in the
      biomarkers found between the bulk and capsulated samples. Our data indicate that
      both the aqueous and methanol extracts of all 5 uva-ursi products showed high
      cytochrome P450 isozyme inhibition, with the exception of the methanol extracts
      against cytochromes P3A4 and P19, which had low to moderate activity. The aqueous
      extracts of uva-ursi showed an inhibitory effect on Rh123 efflux by P-gp at 1 h
      and an inductive effect at 18 h for both cell lines. Our results show that the
      uva-ursi herbal products tested here have pharmacological properties, including
      the potential capacity to affect drug safety and efficacy. Further studies are
      warranted against a wider range of cytochrome P450 isozymes and to determine
      whether these effects are clinically significant.

PMID- 18066113
TI  - Gene response of human monocytic cells for the detection of antimigraine activity
      of feverfew extracts.
AB  - The herb feverfew is a folk remedy for various conditions, including
      inflammation, fever, psoriasis, rheumatism, and asthma. Like many herbal
      medicines, feverfew's mechanisms of action in the human body are largely unknown
      and its active ingredients remain elusive. Very often, different extraction
      methods of herb material produce different physical and biochemical properties
      and variation in clinical efficacy. We identified 3 major methods of extraction
      for feverfew aerial parts and used microarray technology to test the hypothesis
      that extracts produced by different methods elicit different gene expression
      profiles. We have identified approximately 200 genes that are consistently
      regulated by the 2 presumptive active antimigraine feverfew extracts but not
      associated with the inactive extract. Our results suggest that the presumptive
      active feverfew extracts potently stimulate more genes in human cells than the
      inactive extracts. We also identified several genes as unique signatures for
      these active extracts. All 3 feverfew extracts exhibited similar blockades on
      lipopolysaccharide-mediated TNF-alpha (tumor necrosis factor alpha) release,
      implicating that TNF-alpha is not responsible for the differences in the effects
      of the 3 feverfew extracts in human cells. In contrast, the active extracts more
      effectively suppressed CCL2 (also known as monocyte chemoattractant protein 1,
      MCP-1) than the inactive extracts, suggesting that CCL2 is a potential cellular
      target for feverfew's antimigraine effects.

PMID- 18066114
TI  - Antidiabetic properties of polysaccharide- and polyphenolic-enriched fractions
      from the brown seaweed Ascophyllum nodosum.
AB  - We screened seaweed species from Atlantic Canada for antidiabetic activity by
      testing extracts for alpha-glucosidase inhibitory effect and glucose uptake
      stimulatory activity. An aqueous ethanolic extract of Ascophyllum nodosum was
      found to be active in both assays, inhibiting rat intestinal alpha-glucosidase
      (IC50 = 77 microg/mL) and stimulating basal glucose uptake into 3T3-L1 adipocytes
      during a 20-minute incubation by about 3-fold (at 400 microg/mL extract).
      Bioassay-guided fractionation of the A. nodosum extract showed that alpha
      glucosidase inhibition was associated with polyphenolic components in the
      extract. These polyphenolics, along with other constituents appeared to be
      responsible for the stimulatory activity on glucose uptake. However, attempts to
      further concentrate this activity through fractionation techniques were
      unsuccessful. A crude polyphenol extract (PPE), an enriched polyphenolic fraction
      (PPE-F1) and a polysaccharide extract (PSE) were prepared from commercial A.
      nodosum powder and administered to streptozotocin-diabetic mice for up to 4-weeks
      by daily gavage at 200 mg/kg body mass. PPE and PPE-F1 improved fasting serum
      glucose level in diabetic mice; however, the effect was only statistically
      significant at day 14. In addition, PPE-F1 was shown to blunt the rise in blood
      glucose after an oral sucrose tolerance test in diabetic mice. Mice treated with
      PPE and PPE-F1 had decreased blood total cholesterol and glycated serum protein
      levels compared with untreated diabetic mice, whereas PPE also normalized the
      reduction in liver glycogen level that occurred in diabetic animals. All 3 A.
      nodosum preparations improved blood antioxidant capacity.

PMID- 18066115
TI  - Plant phenolics regulate neoplastic cell growth and survival: a quantitative
      structure-activity and biochemical analysis.
AB  - The anti-tumour activities of many plant phenolics at high concentrations (>100
      micromol/L) suggest their potential use as dietary supplements in cancer
      chemoprevention and cancer chemotherapy. However, it is not clear what impact
      phenolic compounds have at the physiological concentrations obtained through
      consumption of high phenolic diets on neoplastic cells. In the present study, 54
      naturally occurring phenolics were evaluated at physiologically relevant
      concentrations for their capacity to alter PC12 cell viability in response to
      serum deprivation, the chemotherepeutic agent etoposide, and the apoptogen C2
      ceramide. Surprisingly, novel mitogenic, cytoprotective, and antiapoptotic
      activities were detected. Quantitative structure-activity relationship modelling
      indicated that many of these activities could be predicted by compound
      lipophilicity, steric bulk, and (or) antioxidant capacity, with the exception of
      inhibition of ceramide-induced apoptosis. Where quantitative structure-activity
      relationship analysis was insufficient, biochemical assessment demonstrated that
      the benzoate orsellinic acid blocked downstream caspase-12 activation following
      ceramide challenge. These findings demonstrate substantive mitogenic,
      cytoprotective, and antiapoptotic biological activities of plant phenolics on
      neoplastic cells at physiologically relevant dietary concentrations that should
      be considered in chemopreventive and chemotherapeutic strategies.

PMID- 18066116
TI  - Survey of bioactive components in Western Canadian berries.
AB  - Berries native to Western Canada were analyzed for total anthocyanins, total
      phenolics, and trolox equivalent antioxidant activity (TEAC). Values ranged from
      1.60 to 9.55 mmol trolox equivalent per 100 g fresh mass. Anthocyanin content
      ranged from 41.6 (in red twinberries) to 1081 mg cyanidin-3-glucoside equivalents
      per 100 g fresh mass (in honeysuckle fruits). Honeysuckle fruits contained the
      highest amount of total polyphenols, 1111 mg gallic acid equivalents per 100 g,
      among analyzed fruits. Additionally, anthocyanins in the investigated berries
      were identified and characterized by HPLC - electrospray ionization - tandem mass
      spectrometric method coupled with diode array detection. The number of
      anthocyanins varied from 4 in saskatoon berries (Amelanchier alnifolia Nutt.) to
      20 in bilberries (Vaccinum myrtilloides Michx.). In all the samples analyzed, 6
      common anthocyanidins:, cyanidin, delphinidin, pelargonidin, petunidin, peonidin,
      and malvidin, were found. Half the analyzed berries contained acylated
      anthocyanins, but a significant amount was found only in bilberries. The analyzed
      berry seed oils contained high amounts of unsaturated fatty acids (over 90%), but
      only the golden currant seed oil contained gamma-linolenic acid.

PMID- 18066117
TI  - Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB
      231 human breast cancer cells: an in vitro study.
AB  - Breast cancer cell cultures were exposed to different concentrations of black
      cohosh, estradiol (E2), and tamoxifen to examine the effect on cell
      proliferation; cytotoxicity was assessed by using sulforhodamine B (SRB) dye
      solution. E2 (10(-10) - 10(-8) mol/L) markedly stimulated the proliferation of
      MCF-7 cells (p < 0.01). Tamoxifen stimulated MCF-7 cell proliferation at 10(-6)
      mol/L and 10(-5) mol/L (p < 0.005) but inhibited in a dose-dependent fashion the
      proliferative effect of E2 (p < 0.001). Black cohosh alone did not show any
      stimulatory effect, but exhibited a cytotoxic effect, which was significant at
      10(3) microg/mL (p < 0.001). Adding black cohosh at 10(0)-10(3) microg/mL to E2
      at 10(-9) mol/L also resulted in a dose-dependent inhibition of E2 proliferative
      effect. Interestingly, the combination of black cohosh (10(0)-10(3) microg/mL)
      with increasing tamoxifen concentrations further inhibited MCF-7 cell growth. On
      MDA-MB-231 cells, neither E2 nor tamoxifen displayed any detectable effect.
      However, black cohosh inhibited MDA-MB-231 cell proliferation at 10(3) microg/mL
      (p < 0.05), and this inhibitory effect was enhanced by increasing tamoxifen
      concentrations. This study reveals a cytotoxic effect of black cohosh on both
      estrogen-sensitive and estrogen-insensitive breast cancer cells and a synergism
      with tamoxifen for inhibition of cancerous cell growth.

PMID- 18066118
TI  - Xanthatin and xanthinosin from the burs of Xanthium strumarium L. as potential
      anticancer agents.
AB  - Xanthatin and xanthinosin, 2 sesquiterpene lactones isolated from the burs of
      Xanthiun strumarium L. (cocklebur), showed moderate to high in vitro cytotoxic
      activity in the human cancer cell lines WiDr ATCC (colon), MDA-MB-231 ATCC
      (breast), and NCI-417 (lung). Xanthatin and xanthinosin were purified as the
      result of a multi-screening bioassay-guided study of wild plant species of the
      family Asteraceae, collected from various sites in Saskatchewan, Canada. Seventy
      five extracts at a single concentration of 100 microg/mL were evaluated for in
      vitro cytotoxicity to the human cancer cell lines used. The chloroform extract of
      Carduus nutans L. (nodding thistle) aerial parts (IC50, 9.3 microg/mL) and the
      hexane extract of Echinacea angustifolia DC. (narrow-leaved purple coneflower)
      root (IC50, 4.0 microg/mL) were moderately to highly cytotoxic to the lung cancer
      cell line. The chloroform extracts of X. strumarium L. burs and Tanacetum vulgare
      L. (tansy) aerial parts exhibited the highest cytotoxicity for all cell lines
      tested; their IC50 values, obtained from multidose testing, ranged from 0.1 to
      6.2 microg/mL (X. strumarium) and from 2.4 to 9.1 microg/mL (T. vulgare). Further
      purification of the chloroform fraction of X. strumarium yielded xanthatin and
      xanthinosin in high yields. This is the first time that these compounds have been
      reported in the burs of X. strumarium. Their IC50 values are also reported
      herein.

PMID- 18066119
TI  - Characterizing the mechanism for ginsenoside-induced cytotoxicity in cultured
      leukemia (THP-1) cells.
AB  - Pure ginsenoside standards (saponins Rh2, PD, and PT), along with an Rh2-enhanced
      North American ginseng (Panax quinquefolius) leaf extract (LFRh2), were tested
      for cytotoxic activity in cultured THP-1 leukemia cells. Thermal treatment of
      ginseng leaf resulted in production of both Rh2 and Rg3 content that was
      confirmed by liquid chromatography - mass spectrometry (LC-MS). Flow cytometry of
      cells stained with annexin V - fluorescein isothiocyanate and propidium iodide
      showed that the LFRh2 significantly (p < or = 0.05) increased apoptosis (18% +/-
      0.4%) after 23 h at a concentration that inhibited cell viability by 50% (LC50
      (72 h) = 52 microg/mL. In comparison, a similar significant (p < or = 0.05)
      increase in apoptotic cell numbers occurred at 41 h of exposure for pure
      ginsenoside standards, PD (LC50 (72 h) = 13 microg/mL), PT (LC50 (72 h) = 19
      microg/mL), and Rh2 (LC50 (72 h) = 15 microg/mL). Although no further increase in
      apoptosis was observed in THP-1 cells after exposure to increasing concentrations
      of LFRh2 and pure Rh2, PD, and PT standards, a significant (p < 0.05) increase in
      the percentage of necrotic cells did occur after exposure of cells to different
      ginsenosides at elevated concentrations. THP-1 caspase-3 activity was greatest (p
      <or= 0.05) with Rh2 (7.6 +/- 1.1 nmol/L pNA), followed by LFRh2 (5.9 +/- 1.0
      nmol/L pNA) and PT (5.0 +/- 0.8 nmol/L pNA), whereas PD was similar to control
      cells. We define for the first time the proportion of apoptotic to necrotic
      events that characterize the relative cytotoxicity and reduced cell proliferation
      of different ginsenosides in cultured THP-1 cells. Moreover, thermal treatment of
      North American ginseng leaf produced a marked transformation of ginsenoside,
      largely attributable to an increase in Rh2 content. This change was associated
      with cytotoxic properties in THP-1 cell that were related to alterations in cell
      membrane properties, which were also obtained with the pure ginsenosides PD, PT,
      and Rh2.

PMID- 18066120
TI  - Adjuvant activities of saponins from the root of Polygala senega L.
AB  - Eight pure triterpenoid saponin compounds isolated from the root of Polygala
      senega L., a plant indigenous to the Canadian prairies, were evaluated for their
      immunological activity in mouse models. The specific antibody responses of the
      IgG2a subclass increased significantly when isolated P. senega saponins were used
      as adjuvants in the immunization of mice with OVA antigen. In addition, increased
      IL-2 levels were observed in spleen cell cultures from P. senega saponin
      immunized mice after in vitro secondary antigen stimulation. The saponins were
      tested for their toxicity in mice by using a haemolytic activity assay and found
      to be less toxic than Quillaja saponaria saponins that have long been used as
      adjuvants in vaccine formulations. This study has shown the potential of P.
      senega saponins to be considered as a natural source of vaccine adjuvants with
      biological activity equivalent to the current commercially available saponin
      adjuvants.

PMID- 18066121
TI  - Echinacea purpurea L. in children: safety, tolerability, compliance, and clinical
      effectiveness in upper respiratory tract infections.
AB  - Echinacea purpurea (L.) Moench was mistakenly taken from North America to Germany
      in 1939 where it was cultivated and various extractions were prepared and
      subsequently used to treat upper respiratory tract infections. Parents often
      administer Echinacea to their children, but safety data on the use of Echinacea
      in Canadian children is lacking. A screening history, physical examination, and
      daily record of symptoms from an initial visit through to a the follow-up visit
      13 days later were used to increase patient safety. Each subject was administered
      an aerial part Echinacea extract. The dose was based on age (2.5 mL three times
      per day for children aged 2-5 years, and 5 mL two times per day for children aged
      6-12 years) and administered for 10 days in an open-label trial. A rating scale
      was used to measure tolerance to the treatment. We assessed the safety and
      compliance of use of the Echinacea extract by measuring the amount of extract
      returned at the end of the study, having the parents complete and return a daily
      symptom diary, and recording the subjects' use of other natural health products
      or medications during the trial. Clinical effectiveness of the Echinacea extract
      could not be accurately assessed because of the small trial size and because the
      extract had been administered when some of the subjects had an upper respiratory
      tract infection that had begun 1 or more days prior to the study; however, each
      subject's symptoms improved. No allergic or adverse reaction occurred and no
      safety issues arose.

PMID- 18066122
TI  - Medicinal plants of Cree communities (Quebec, Canada): antioxidant activity of
      plants used to treat type 2 diabetes symptoms.
AB  - Traditional medicines (TM) used to treat symptoms of diabetes by two Cree
      communities were assessed for their free radical scavenging activity using the
      stable 1,1-diphenyl-2-picrylhydrazyl radical, and their ability to protect human
      low-density lipoprotein from Cu2+-mediated oxidation by measuring lag time before
      the appearance of conjugated dienes and formation of thiobarbituric acid-reactive
      substances. Water-soluble phenolic content was also measured. A total of 20
      medicinal plants from Whapmagoostui and 16 from Mistissini were compared with 16
      extracts of plants that were not used medicinally. Medicinal plant extracts,
      particularly those from Larix laricina, displayed high antioxidant activity,
      comparable with ascorbic acid, Trolox, and the known antioxidant flavonoids
      quercetin, epicatechin, catechin. Extracts of Pinaceae and Ericaceae contained
      the highest levels of phenolics. Factors such as season and area of plant
      collection, as well as the plant part from which the extract was derived,
      affected antioxidant activity. Positive correlations were found between the
      established traditional knowledge of Cree Elders and Healers and the antioxidant
      activity for medicinal plants used in Mistissini (r = 0.3134; p = 0.058) and in
      Whapmagoostui (r = 0.5165; p = 0.001). Significant correlations between phenolic
      content were also seen with the existing ethnobotanical data (r = 0.5015; p =
      0.003) and bioassays (r = 0.4178; p = 0.003). These results indicate that a clear
      majority of plants used by the Cree are excellent sources of antioxidants.

PMID- 18066123
TI  - Adventures in drug disposition: pas seulement pate de foie.
AB  - Interindividual variability in drug disposition and effect has served to confound
      the optimization of drug therapy. Over my career, I have focused on delineating
      mechanisms that contribute to this variability, with the goal of improving the
      benefit : risk ratio when drug therapy is chosen as an intervention strategy. In
      this manuscript, I present some of our experimental findings that I believe have
      contributed to an increased understanding of variability in drug disposition and
      efficacy.

PMID- 18066124
TI  - Sex differences in mouse models of asthma.
AB  - Differences in disease susceptibility and prognosis between men and women are
      known to occur in the incidence and development of neurodegenerative,
      cardiovascular, and immunological disorders. In the lung there are also sex-based
      differences in the incidence, prevalence, and pathogenesis of lung cancer, cystic
      fibrosis, COPD, and asthma. In the general population, sex-based differences in
      asthma have been shown by epidemiologic studies, but unfortunately these studies
      are not consistent in their conclusions. This variability in human
      epidemiological studies justifies the need for more focused studies of the
      effects of specific hormones. Such specific mechanistic studies can most easily
      be performed in animal models, and since mouse models have the potential for
      separating specific genetic factors from environmental and exogenous factors,
      this species has become increasingly important in the design, analysis, and
      interpretation of asthma research. This review will document the male and female
      differences in airway function of naive and sensitized mouse models, as well as
      the great variability in the functional measurements of airway tone. Until the
      situation is better understood, this variability between males and females should
      be kept in mind when designing, analyzing, and interpreting studies of smooth
      muscle responses in animal models and human subjects.

PMID- 18066126
TI  - Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion
      injury by opening K ATP channels.
AB  - The present study was undertaken to investigate the protective effect of H2S
      against myocardial ischemia-reperfusion (I/R) injury and its possible mechanism
      by using isolated heart perfusion and patch clamp recordings. Rat isolated hearts
      were Langendorff-perfused and subjected to a 30-minute ischemia insult followed
      by a 30-minute reperfusion. The heart function was assessed by measuring the
      LVDP, +/-dP/dt max, and the arrhythmia score. The results showed that the
      treatment of hearts with a H2S donor (40 micromol/L NaHS) during reperfusion
      resulted in significant improvement in heart function compared with the I/R group
      (LVDP recovered to 85.0% +/- 6.4% vs. 35.0% +/- 6.1%, +dP/dt max recovered to
      80.9% +/- 4.2% vs. 43.0% +/- 6.4%, and -dP/dt max recovered to 87.4% +/- 7.3% vs.
      53.8% +/- 4.9%; p < 0.01). The arrhythmia scores also improved in the NaHS group
      compared with the I/R group (1.5 +/- 0.2 vs. 4.0 +/- 0.4, respectively; p <
      0.001). The cardioprotective effect of NaHS during reperfusion could be blocked
      by an ATP-sensitive potassium channel (K ATP) blocker (10 micromol/L
      glibenclamide). In single cardiac myocytes, NaHS increased the open probability
      of K ATP channels from 0.07 +/- 0.03 to 0.15 +/- 0.08 after application of 40
      mumol/L NaHS and from 0.07 +/- 0.03 to 0.36 +/- 0.15 after application of 100
      mumol/L NaHS. These findings provide the first evidence that H2S increases the
      open probability of K ATP in cardiac myocytes, which may be responsible for
      cardioprotection against I/R injury during reperfusion.

PMID- 18066125
TI  - Homocysteine stimulates NADPH oxidase-mediated superoxide production leading to
      endothelial dysfunction in rats.
AB  - Elevation of blood homocysteine (Hcy) levels (hyperhomocysteinemia) is a risk
      factor for cardiovascular disorders. We previously reported that oxidative stress
      contributed to Hcy-induced inflammatory response in vascular cells. In this
      study, we investigated whether NADPH oxidase was involved in Hcy-induced
      superoxide anion accumulation in the aorta, which leads to endothelial
      dysfunction during hyperhomocysteinemia. Hyperhomocysteinemia was induced in rats
      fed a high-methionine diet. NADPH oxidase activity and the levels of superoxide
      and peroxynitrite were markedly increased in aortas isolated from
      hyperhomocysteinemic rats. Expression of the NADPH oxidase subunit p22 phox
      increased significantly in these aortas. Administration of an NADPH oxidase
      inhibitor (apocynin) not only attenuated aortic superoxide and peroxynitrite to
      control levels but also restored endothelium-dependent relaxation in the aortas
      of hyperhomocysteinemic rats. Transfection of human endothelial cells or vascular
      smooth muscle cells with p22 phox siRNA to inhibit NADPH oxidase activation
      effectively abolished Hcy-induced superoxide anion production, thus indicating
      the direct involvement of NADPH oxidase in elevated superoxide generation in
      vascular cells. Taken together, these results suggest that Hcy-stimulated
      superoxide anion production in the vascular wall is mediated through the
      activation of NADPH oxidase, which leads to endothelial dysfunction during
      hyperhomocysteinemia.

PMID- 18066127
TI  - Role of calmodulin and myosin light chain kinase in the activation of carbachol
      activated cationic current in murine ileal myocytes.
AB  - We investigated the effect of calmodulin (CaM) and myosin light chain kinase
      (MLCK) on murine ileal myocytes using the whole-cell patch-clamp technique. Under
      the voltage clamp, at the holding potential of -60 mV, 50 micromol/L carbachol
      (CCh) induced inward currents (I CCh), and spontaneous decay of I CCh occurred.
      The peak inward currents induced by the repetitive application of CCh (50
      micromol/L) tended to decrease in amplitude. Intracellular application of 0.2
      mmol/L guanosine 5'-O-(gamma-thio)triphosphate (GTP gammaS) from the patch
      electrode induced an inward current at a holding potential of -60m V, and the
      peak inward currents induced by the repetitive application of Cs tended to
      decrease slightly in amplitude. The amplitude of I CCh was reduced by
      pretreatment either with W-7, trifluoroperazine, W-5, and melittin (CaM
      inhibitors) or with ML-7 and ML-9 (selective MLCK inhibitors), and the inhibitory
      effects were reversible. However, when we pretreated with 50 micromol/L W-7 or 5
      micromol/L ML-7 on GTP gammaS-induced inward currents, almost no inhibition was
      observed in the inward currents. Application of both Rho kinase inhibitor and
      MLCK inhibitor inhibited GTP gammaS-induced currents. We conclude that CaM and
      MLCK modulate the activation process of I CCh in murine ileal myocytes and
      suggest that the classical type transient receptor potential (TRPC) channel 5
      might be a candidate for nonselective cationic currents (NSCC) activated by
      muscarinic stimulation in gastrointestinal smooth muscle cells.

PMID- 18066128
TI  - Spontaneous temperature changes in the 2-vessel occlusion model of cerebral
      ischemia in rats.
AB  - Transient global ischemia (ISC) in rats and humans causes selective and delayed
      neuronal death in the hippocampal CA1 sector. It is clear from rodent studies
      that hyperthermia aggravates, whereas hypothermia lessens, this injury. In this
      study we sought to relate core (Tc) and brain (Tb) temperature, measured via
      telemetry probes, after ISC produced in rats by bilateral common carotid artery
      occlusion combined with systemic hypotension (2-VO model). We also tested whether
      spontaneous postischemic temperature fluctuations occurred and whether they were
      related to cell death as previous studies indicate. We report that Tc and Tb
      readings are similar and are highly correlated before and after 10 min of 2-VO
      ISC. In the second experiment, rats were subjected to 8, 9, or 10 min of 2-VO
      ISC. Despite a range in CA1 injury among these animals, there was no evidence of
      post-ISC hyperthermia, contrary to earlier work, and neither temperature nor the
      physiological variables measured during ISC (e.g., glucose) predicted injury. Our
      findings suggest that, under the present conditions, 2-VO rats do not experience
      postoperative hyperthermia, which can be adequately measured with Tc telemetry
      probes.

PMID- 18066129
TI  - From type 2 diabetes to antioxidant activity: a systematic review of the safety
      and efficacy of common and cassia cinnamon bark.
AB  - Common (Cinnamomum verum, C. zeylanicum) and cassia (C. aromaticum) cinnamon have
      a long history of use as spices and flavouring agents. A number of
      pharmacological and clinical effects have been observed with their use. The
      objective of this study was to systematically review the scientific literature
      for preclinical and clinical evidence of safety, efficacy, and pharmacological
      activity of common and cassia cinnamon. Using the principles of evidence-based
      practice, we searched 9 electronic databases and compiled data according to the
      grade of evidence found. One pharmacological study on antioxidant activity and 7
      clinical studies on various medical conditions were reported in the scientific
      literature including type 2 diabetes (3), Helicobacter pylori infection (1),
      activation of olfactory cortex of the brain (1), oral candidiasis in HIV (1), and
      chronic salmonellosis (1). Two of 3 randomized clinical trials on type 2 diabetes
      provided strong scientific evidence that cassia cinnamon demonstrates a
      therapeutic effect in reducing fasting blood glucose by 10.3%-29%; the third
      clinical trial did not observe this effect. Cassia cinnamon, however, did not
      have an effect at lowering glycosylated hemoglobin (HbA1c). One randomized
      clinical trial reported that cassia cinnamon lowered total cholesterol, low
      density lipoprotein cholesterol, and triglycerides; the other 2 trials, however,
      did not observe this effect. There was good scientific evidence that a species of
      cinnamon was not effective at eradicating H. pylori infection. Common cinnamon
      showed weak to very weak evidence of efficacy in treating oral candidiasis in HIV
      patients and chronic salmonellosis.

PMID- 18066130
TI  - Effect of Ginkgo biloba extract on oxidative metabolism of valproic acid in
      hepatic microsomes from donors with the CYP2C9*1/*1 genotype.
AB  - We investigated the effect of Ginkgo biloba extracts and some of its individual
      constituents on the oxidative metabolism of valproic acid (VPA) in hepatic
      microsomes from donors with the CYP2C9*1/*1 genotype. G. biloba extract decreased
      4-ene-VPA, 3-OH-VPA, 4-OH-VPA, and 5-OH-VPA formation with mean (+/- SE) IC50
      values of 340 +/- 40 microg/mL, 370 +/- 100 microg/mL, 180 +/- 30 microg/mL, and
      210 +/- 20 microg/mL, respectively. This was associated with inhibition of not
      only CYP2C9*1, but also CYP2A6 and CYP2B6. Bilobalide, ginkgolide A, ginkgolide
      B, ginkgolide C, ginkgolide J, quercetin-3-O-rutinoside, kaempferol-3-O
      rutinoside, and isorhamnetin-3-O-rutinoside were not responsible for the
      inhibition of VPA metabolism by the extract. When analyzed as the sum of the
      aglycone and total glycosides present in the extract, quercetin decreased 4-ene
      VPA, 4-OH-VPA, and 5-OH-VPA formation by 76%, 51%, and 70%, respectively,
      kaempferol decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA formation by 65%, 46%, and
      49%, respectively, and isorhamnetin decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA
      formation by 29%, 26%, and 31%, respectively. The 3 aglycones did not affect 3-OH
      VPA formation. In summary, G. biloba extract decreased hepatic microsomal
      formation of 4-ene-VPA, 4-OH-VPA, 5-OH-VPA, and 3-OH-VPA, but the effect was not
      due to the terpene trilactones or flavonol glycosides investigated in our study.

PMID- 18066131
TI  - Five batches representative of Ontario-grown American ginseng root produce
      comparable reductions of postprandial glycemia in healthy individuals.
AB  - Evidence indicates that the glycemia-lowering effect of American ginseng root may
      be batch dependent. We therefore evaluated the effect of 5 root batches,
      representative of Ontario-grown American ginseng, on postprandial glucose and
      insulin indices. Twelve healthy subjects (5 male, 7 female), mean +/- SE age 26.5
      +/- 2 years, body mass index 23.96 +/- 3.41 kg/m2, fasting blood glucose 4.77 +/-
      0.04 mmol/L, were assigned to consume 9 g of American ginseng from 5 farms (A-E),
      administered in randomized sequence on 5 separate visits, and a water-control
      during the 6th and last visit. Treatments were consumed 40 min before a 2-hour 75
      gram oral glucose tolerance test. Plasma glucose and insulin were measured at
      baseline, before, and during the test. Compared with control, batches A and C
      reduced glucose incremental area under the curve (IAUC) by 35.2% (156 vs. 240
      mmol.min/L) and 32.6% (162 vs. 240 mmol.min/L), respectively. Batches A, C, and E
      reduced incremental peak glucose by 1.3, 1.2, and 1.1 mmol/L, respectively. Batch
      C reduced the insulin IAUC by 27.7% (15.8 vs. 21.8 nmol.min/L). Effects on
      glucose and insulin parameters were not different across ginseng treatments. The
      mean of the 5 ginseng treatments reduced peak postprandial glucose by 1.0 mmol/L,
      glucose IAUC by 27.7% (173 vs. 240 mmol.min/L), and insulin IAUC by 23.8% (16.6
      vs. 21.8 nmol.min/L) relative to control. (All results statistically significant
      at p < 0.05.) American ginseng decreased postprandial glycemia and insulinemia;
      however, 40% of the batches did not reduce glycemia with the anticipated
      magnitude, irrespective of their saponin composition.

PMID- 18066132
TI  - Bioactivity-guided isolation of the active compounds from Rosa nutkana and
      quantitative analysis of ascorbic acid by HPLC.
AB  - Rosa nutkana Presl. (Rosaceae) is distributed abundantly throughout central and
      southern areas of British Columbia, Canada. Aboriginal people in the Pacific
      Northwest have traditionally used R. nutkana as a food, medicine, and source of
      cultural material. The methanolic extract of the fruits of R. nutkana was
      previously found to have inhibitory activity against methicillin-resistant
      Staphylococcus aureus (MRSA). In our study, bioactivity-guided fractionation of
      the methanol extract from R. nutkana led to the isolation of the following 10
      compounds: (i) tormentic acid, (ii) euscaphic acid, (iii) ursolic acid, (iv)
      maslinic acid, (v) quercetin, (vi) catechin gallate, (vii) quercetin-3-O
      glucoside, (viii) 1,2,3,4,6-penta-O-galloyl-beta-D-glucoside, (ix) L-ascorbic
      acid (vitamin C), and (x) 1,6-digalloyl-beta-D-glucoside. Structures were
      elucidated by ultraviolet, infrared, mass spectrometry, and nuclear magnetic
      resonance data, as well as by comparison with those of the literature. The
      compounds quercetin, catechin gallate, quercetin-3-O-glucoside, 1,2,3,4,6-penta-O
      galloyl-beta-D-glucoside, and 1,6-digalloyl-beta-D-glucoside exhibited weak
      antibacterial activity against MRSA. Our research demonstrates the value of
      traditional knowledge held by Aboriginal people in the Pacific Northwest with
      respect to uses of R. nutkana. Some described uses in the ethnobotanical
      literature correspond to activities observed under laboratory conditions. Further
      work on British Columbia Rosa spp. may contribute to identifying other potential
      therapeutic uses.

PMID- 18066133
TI  - Clinical safety and efficacy of NG440: a novel combination of rho iso-alpha acids
      from hops, rosemary, and oleanolic acid for inflammatory conditions.
AB  - In this report, we examine the clinical safety and efficacy of NG440, a
      phytochemical-based antiinflammatory formula consisting of a combination of rho
      iso-alpha acids from hops, rosemary, and oleanolic acid. In a previous study, we
      demonstrated that NG440 significantly decreased pain by 50% in patients with
      osteoarthritis. Consistent with these data, results from a multicentre trial
      indicate that NG440 reduced pain scores in patients with joint discomfort, as
      measured by VAS (visual analog scale) methodology. As demonstrated in an ex vivo
      clinical study, these effects on pain relief may be due to reduced inflammatory
      cytokine production including lower prostaglandin E2 formation. Finally, strong
      data exist to suggest that NG440 is a safe formula for human consumption. Animal
      toxicity data revealed no adverse effects of NG440 at dosages < or =250 mg.kg
      1.day-1 for 21 days. Furthermore, human trial data suggest that NG440 does not
      negatively impact cardiovascular and gastrointestinal markers normally affected
      by selective COX-2 enzyme inhibitors, including platelet function, blood
      pressure, blood cell count, or fecal calprotectin, a measure of gastrointestinal
      injury. In conclusion, NG440 may serve as a safe and efficacious alternative in
      some areas where specific COX-2 inhibitors have been traditionally used.

PMID- 18066134
TI  - Live encapsulated Lactobacillus acidophilus cells in yogurt for therapeutic oral
      delivery: preparation and in vitro analysis of alginate-chitosan microcapsules.
AB  - Targeted delivery of live microencapsulated bacterial cells has strong potential
      for application in treating various diseases, including diarrhea, kidney failure,
      liver failure, and high cholesterol, among others. This study investigates the
      potential of microcapsules composed of two natural polymers, alginate and
      chitosan (AC), and the use of these artificial cells in yogurt for delivery of
      probiotic Lactobacillus acidophilus bacterial live cells. Results show that the
      integrity of AC microcapsules was preserved after 76 h of mechanical shaking in
      MRS broth and after 12 h and 24 h in simulated gastric and intestinal fluids.
      Using an in vitro computer-controlled simulated human gastrointestinal (GI)
      model, we found 8.37 log CFU/mL of viable bacterial cells were present after 120
      min of gastric exposure and 7.96 log CFU/mL after 360 min of intestinal exposure.
      In addition, AC microcapsules composed of chitosan 10 and 100 at various
      concentrations were subjected to 4-week storage in 2% milk fat yogurt or 0.85%
      physiological solution. It was found that 9.37 log CFU/mL of cells encapsulated
      with chitosan 10 and 8.24 log CFU/mL of cells encapsulated with chitosan 100 were
      alive after 4 weeks. The AC capsule composed of 0.5% chitosan 10 provided the
      highest bacterial survival of 9.11 log CFU/mL after 4 weeks. Finally, an
      investigation of bacterial viability over 72 h in different pH buffers yielded
      highest survival of 6.34 log CFU/mL and 10.34 log CFU/mL at pH 8 for free and AC
      encapsulated cells, respectively. We conclude from these findings that
      encapsulation allows delivery of a higher number of bacteria to desired targets
      in the GI tract and that microcapsules containing bacterial cells are good
      candidates for oral artificial cells for bacterial cell therapy.

PMID- 18066135
TI  - Pressurized water versus ethanol as a Silybum marianum extraction solvent for
      inhibition of low-density lipoprotein oxidation mediated by copper and J774
      macrophage cells.
AB  - Silybum marianum contains flavonolignans, termed silymarin (SM), that are
      therapeutic agents for many inflammation-based diseases including
      atherosclerosis. Oxidation of human low-density lipoprotein was induced by CuSO4
      or J774 macrophage cells and measured by the formation of thiobarbituric acid
      reactive substances (TBARS). SM was extracted by pressurized hot water (PHWE) or
      ethanol, and the effects of these extracts on TBARS formation were evaluated in
      comparison with those of SM preparations made from blending masses of individual
      flavonolignan standards in ratios identical to those of the water and ethanol
      extracts. Ethanol-extracted SM and its blended counterpart inhibited the
      generation of TBARS by 82% and 43%, respectively, at 150 mumol/L doses. TBARS
      levels in the presence of 150 micromol/L of the PHWE and its blended SM
      counterpart were reduced by 84% and 38%, respectively. Extracts from milk thistle
      fruit displayed higher protective effects than blended SM solutions of the same
      concentration with an identical compositional makeup. The appearance of
      degradation peaks in the water extract did not create any cytotoxic effects.
      Results of this study confirm that PHWE can be used to extract flavonolignans
      from milk thistle and that these extracts may possess therapeutic potential
      different from or beyond that of traditional organic solvent preparations.

PMID- 18066136
TI  - Modulation of apolipoprotein A1 and B, adiponectin, ghrelin, and growth hormone
      concentrations by plant sterols and exercise in previously sedentary humans.
AB  - Plant sterols combined with exercise beneficially alter lipid levels in
      hypercholesterolemic adults. The effect of this combination therapy on other
      indicators of coronary heart disease risk, however, has yet to be determined. The
      objective of this trial was to investigate the effect of plant sterols and
      exercise, alone and in combination, on levels of apolipoprotein (apo) A1 and B,
      adiponectin, ghrelin, and growth hormone in previously sedentary
      hypercholesterolemic adults. In an 8 week, parallel-arm trial, 84 subjects were
      randomized to 1 of 4 groups: combination, exercise, plant sterols, or control.
      Body mass decreased by 1.1% (p < 0.01) and 0.9% (p < 0.05) in the combination and
      exercise group, respectively. Low-density lipoprotein cholesterol levels
      decreased (p < 0.01) by 0.30 mmol/L in the combination group and by 0.49 mmol/L
      in the plant sterol group. High-density lipoprotein cholesterol levels increased
      by 7.5% and 9.5% (p < 0.01) in the combination and exercise groups, respectively.
      Plant sterols increased (p < 0.05) adiponectin levels by 16%. No change in apoA1,
      apoB, ghrelin, or growth hormone levels were noted in any intervention group.
      ApoA1 was correlated with high-density lipoprotein cholesterol (r = 0.33, p =
      0.01), whereas apoB was weakly related to low-density lipoprotein cholesterol
      levels (r = 0.13, p = 0.002). Adiponectin was associated with body mass index (r
      = -0.10, p = 0.006) and high-density lipoprotein cholesterol (r = 0.17, p =
      0.0003). These findings suggest that plant sterols can increase adiponectin
      levels, thereby possibly reducing the risk of future coronary heart disease.

PMID- 18066137
TI  - Studies on antihypertensive and antispasmodic activities of Andropogon muricatus
      Retz.
AB  - The aqueous-methanolic crude extract of Andropogon muricatus (Am.Cr) was
      investigated pharmacologically to determine some of its medicinal uses in
      cardiovascular and gastrointestinal disorders. A series of in vivo and in vitro
      studies were conducted to evaluate dose-dependent effects of Am.Cr on mean
      arterial pressure (MAP), cardiac and vascular contractions, and to further
      investigate the potential mechanism of action. Intravenous administration of
      Am.Cr (10-50 mg/kg) caused a fall (18%-56%) in MAP in normotensive rats under
      anesthesia. When tested in isolated guinea pig atria, Am.Cr (0.03-5.0 mg/mL)
      exhibited a cardiodepressant effect on the rate and force of spontaneous
      contractions. In isolated rabbit aorta, Am.Cr caused inhibition of K+ (80 mmol/L)
      induced contractions at a lower concentration than of phenylephrine. In isolated
      rabbit jejunum preparations, Am.Cr (0.01-0.10 mg/mL) caused relaxation of
      spontaneous and high K+ (80 mmol/L)-induced contractions, suggesting that the
      spasmolytic effect is mediated possibly through calcium channel blockade (CCB).
      The CCB activity was confirmed when pretreatment of the tissue with Am.Cr (0.03
      0.1 mg/mL) shifted the Ca2+ dose-response curves to the right, similar to that
      caused by verapamil. These data indicate that the blood pressure-lowering and
      spasmolytic effects of Am.Cr are mediated possibly through a calcium channel
      blocking activity. Phytochemical screening of Am.Cr revealed the presence of
      phenols, saponins, tannins, and terpenes, which may be responsible for the
      observed vasodilator, cardiodepressant, and antispasmodic activities. This study
      shows potential with respect to its medicinal use in cardiovascular and gut
      disorders.

PMID- 18066138
TI  - Antiatherogenic activity of extracts of Argania spinosa L. pericarp: beneficial
      effects on lipid peroxidation and cholesterol homeostasis.
AB  - Prevention of lipoprotein oxidation by natural compounds may prevent
      atherosclerosis via reducing early atherogenesis. In this study, we investigated
      for the first time the beneficial properties of methanolic extract of argania
      pericarp (MEAP) towards atherogenesis by protecting human low-density lipoprotein
      (LDL) against oxidation while promoting high-density lipoprotein (HDL)-mediated
      cholesterol efflux. By measuring the formation of malondialdehyde (MDA) and
      conjugated diene as well as the lag phase and the progression rate of lipid
      peroxidation, the MEAP was found to possess an inhibitory effect. In addition,
      MEAP reduced the rate of disappearance of alpha-tocopherol as well as the apoB
      electrophoretic mobility in a dose-dependent manner. These effects are related to
      the free radical scavenging and copper-chelating effects of MEAP. In terms of
      cell viability, MEAP has shown a cytotoxic effect (0-40 microg/mL). Incubation of
      3H-cholesterol-loaded J774 macrophages with HDL in the presence of increasing
      concentrations of MEAP enhanced HDL-mediated cholesterol efflux independently of
      ABCA1 receptor pathways. Our findings suggest that argania seed pericarp provides
      a source of natural antioxidants that inhibit LDL oxidation and enhance
      cholesterol efflux and thus can prevent development of cardiovascular diseases.

PMID- 18066139
TI  - Protein-source tryptophan as an efficacious treatment for social anxiety
      disorder: a pilot study.
AB  - Until recently, intact protein that is rich in tryptophan was not seen as an
      alternative to pharmaceutical-grade tryptophan because protein also contains
      large neutral amino acids (LNAAs) that compete for transport sites across the
      blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a
      rich source of tryptophan with approximately 22 mg/g protein) is combined with
      glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical
      effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective
      and subjective measures of anxiety in those suffering from social phobia (also
      known as social anxiety disorder) were employed to measure changes in anxiety in
      response to a stimulus as part of a double-blind, placebo-controlled, crossover
      study with a wash-out period of 1 week between study sessions. Subjects were
      randomly assigned to start with either (i) protein-source tryptophan (deoiled
      gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week
      after the initial session, subjects returned for a follow-up session and received
      the opposite treatment of that received at the first session. All 7 subjects who
      began the study completed the 2-week protocol. Protein-source tryptophan with
      carbohydrate, but not carbohydrate alone, resulted in significant improvement on
      an objective measure of anxiety. Protein-source tryptophan combined with a high
      glycemic carbohydrate is a potential anxiolytic to those suffering from social
      phobia.

PMID- 18066141
TI  - XP-828L (Dermylex), a new whey protein extract with potential benefit for mild to
      moderate psoriasis.
AB  - Natural health products (NHPs) or complementary and alternative medicine (CAM)
      are commonly used to prevent disorders or support the usual treatments of many
      diseases. XP-828L, a whey protein extract, has demonstrated potential benefits
      for the treatment of mild to moderate psoriasis. The aim of this study was to
      analyze further clinical data that demonstrated the clinical benefits and safety
      of the XP-828L in patients with psoriasis and the potential mechanism of action
      of this product in vitro. Oral administration (2.5 g, twice a day, over 112 days)
      of XP-828L in 42 human subjects with mild to moderate psoriasis improved their
      PGA scores (physician's global assessment). Moreover, no significant changes in
      haematology or hepatic and renal parameters were observed throughout the study
      period, indicating the safety of the product. In vitro experiments showed that XP
      828L decreased the proliferation of concanavalin A (ConA)-stimulated murine
      splenocytes and their production of interleukin (IL)-2 and interferon (IFN)
      gamma. Although the in vivo mechanism of action of XP-828L remains unknown, XP
      828L represents an NHP to be used as an alternative or concomitant treatment for
      mild to moderate psoriasis and potentially for other immune-mediated diseases.

PMID- 18066140
TI  - Effects of traditionally used anxiolytic botanicals on enzymes of the gamma
      aminobutyric acid (GABA) system.
AB  - In Canada, the use of botanical natural health products (NHPs) for anxiety
      disorders is on the rise, and a critical evaluation of their safety and efficacy
      is required. The purpose of this study was to determine whether commercially
      available botanicals directly affect the primary brain enzymes responsible for
      gamma-aminobutyric acid (GABA) metabolism. Anxiolytic plants may interact with
      either glutamic acid decarboxylase (GAD) or GABA transaminase (GABA-T) and
      ultimately influence brain GABA levels and neurotransmission. Two in vitro rat
      brain homogenate assays were developed to determine the inhibitory concentrations
      (IC50) of aqueous and ethanolic plant extracts. Approximately 70% of all extracts
      that were tested showed little or no inhibitory effect (IC50 values greater than
      1 mg/mL) and are therefore unlikely to affect GABA metabolism as tested. The
      aqueous extract of Melissa officinalis (lemon balm) exhibited the greatest
      inhibition of GABA-T activity (IC50 = 0.35 mg/mL). Extracts from Centella
      asiatica (gotu kola) and Valeriana officinalis (valerian) stimulated GAD activity
      by over 40% at a dose of 1 mg/mL. On the other hand, both Matricaria recutita
      (German chamomile) and Humulus lupulus (hops) showed significant inhibition of
      GAD activity (0.11-0.65 mg/mL). Several of these species may therefore warrant
      further pharmacological investigation. The relation between enzyme activity and
      possible in vivo mode of action is discussed.

PMID- 18066142
TI  - Postmarket surveillance of natural health products in Canada: clinical and
      federal regulatory perspectives.
AB  - Postmarket surveillance, particularly adverse reactions (ARs), forms an integral
      part of the ongoing safety evaluation for natural health products (NHPs). ARs can
      be related to many factors, including inherent toxicity, misuse,
      hypersensitivity, NHP-drug interactions, or product quality. High consumer use
      and limited safety and efficacy data from human clinical trials for many NHPs
      present a challenge to consumers, healthcare practitioners, and federal
      regulators. Canada's Natural Health Products Regulations mandate NHPs to be
      licensed. As the currently available unauthorized NHPs are being brought into
      compliance in Canada, the transition has produced some challenges, requiring
      ongoing public communication and education to promote the safe use of NHPs. This
      article will highlight Health Canada's key postmarket initiatives in
      strengthening the regulation of NHPs.

PMID- 18066143
TI  - Fermented Canadian lowbush blueberry juice stimulates glucose uptake and AMP
      activated protein kinase in insulin-sensitive cultured muscle cells and
      adipocytes.
AB  - Extracts of the Canadian lowbush blueberry (Vaccinium angustifolium Ait.) have
      recently been demonstrated to possess significant antidiabetic potential, in
      accordance with the traditional use of this plant as an antidiabetic natural
      health product. Fermentation of blueberry juice with the Serratia vaccinii
      bacterium is known to modify the phenolic content and increase antioxidant
      activity. The present study evaluated the effects of fermented blueberry juice on
      glucose uptake, adipogenesis, and the signaling pathways that regulate glucose
      transport in muscle cells and adipocytes. A 6-hour treatment with fermented juice
      potentiated glucose uptake by 48% in C2C12 myotubes and by 142% in 3T3-L1
      adipocytes, in the presence or absence of insulin, whereas nonfermented juice had
      no effect on transport. Fermented juice dramatically inhibited triglyceride
      content during adipogenesis of 3T3-L1 cells. Chlorogenic acid and gallic acid,
      both major phenolic components of fermented juice, had no effect on glucose
      uptake. Western blot analysis of the insulin-independent AMP-activated protein
      kinase revealed increased phosphorylation resulting from a 6-hour treatment. This
      activation or the increase in glucose uptake could not be explained by increased
      cytosolic calcium. Fermentation with S. vaccinii is concluded to confer
      antidiabetic activities to blueberry juice. Although the active principles and
      their mechanisms of action remain to be identified, transformed blueberry juice
      may nevertheless represent a novel complementary therapy and a source of novel
      therapeutic agents against diabetes mellitus.

PMID- 18066145
TI  - The curious arithmetic of optical vortices.
AB  - The superposition of noncoaxial light beams containing screw wave-front
      dislocations is shown to create light patterns with a richer vortex content than
      that given by the arithmetic of the topological charges of the individual beams.
      We report the experimental observation of this phenomenon.

PMID- 18066144
TI  - Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in
      Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal
      products.
AB  - In this study, we used an in vitro Caco-2 cell monolayer model to evaluate
      aqueous extracts of commercial-source goldenseal (Hydrastis canadensis) and milk
      thistle (Silybum marianum) capsule formulations, their marker phytochemicals
      (berberine and silibinin, respectively), as well as dillapiol, vinblastine, and
      the HIV protease inhibitor saquinavir for their ability to modulate CYP3A4 and
      ABCB1 expression after short-term exposure (48 h). Both upregulation and
      downregulation of CYP3A4 expression was observed with extracts of varying
      concentrations of the two natural health products (NHPs). CYP3A4 was highly
      responsive in our system, showing a strong dose-dependent modulation by the
      CYP3A4 inhibitor dillapiol (upregulation) and the milk thistle flavonolignan
      silibinin (downregulation). ABCB1 was largely unresponsive in this cellular model
      and appears to be of little value as a biomarker under our experimental
      conditions. Therefore, the modulation of CYP3A4 gene expression can serve as an
      important marker for the in vitro assessment of NHP-drug interactions.

PMID- 18066146
TI  - Astronomical adaptive optics in parameter space.
AB  - We present a general, undiscretized formulation of astronomical adaptive optics
      that encompasses arbitrary guide star sources and deformable mirror
      configurations. It is shown that wave-front measurements can be represented as
      samples of an integral transform of the turbulence perturbation and also that the
      desired information for adaptive correction is a subset of this transformed
      space. Some properties of this space are explored, and their implications for
      adaptive optics are discussed.

PMID- 18066147
TI  - Fiber Bragg grating sensor for simultaneous measurement of displacement and
      temperature.
AB  - A new approach to measuring displacement and temperature simultaneously by use of
      a specially designed isosceles triangular cantilevered beam as a strain agent is
      demonstrated. A fiber Bragg grating epoxied onto the beam surface is
      experimentally demonstrated to have a temperature sensitivity of ~0.113 nm/
      degrees C below 60 degrees C and a displacement sensitivity of 9.24x10(-2) nm/mm
      .

PMID- 18066148
TI  - Dispersion-managed soliton in optical fibers with zero average dispersion.
AB  - A dispersion-managed optical system with stepwise periodic variation of
      dispersion is studied in the framework of a path-averaged Gabitov-Turitsyn
      equation. The soliton solution is obtained by means of iterating the path
      averaged equation. The dependence of soliton parameters on dispersion map
      strength is investigated, together with the oscillating tails of the soliton.

PMID- 18066149
TI  - Increase of photosensitivity in Ge-doped fibers under strain.
AB  - Straining a Ge-doped optical fiber increases its UV photosensitivity. The speed
      of grating fabrication in a standard AT&T telecommunication fiber increases by 18
      times, while the final refractive-index change is enhanced by a factor of 5.
      Measurements reveal opposite changes in the stress of the fiber core induced by
      UV light in strained and unstrained fibers.

PMID- 18066150
TI  - Multiwavelength erbium-doped fiber ring lasers with overlap-written fiber Bragg
      gratings.
AB  - Eight-wavelength Er-doped fiber lasers with lasing wavelength separations of ~1.6
      and ~0.8 nm , respectively, have been achieved by use of overlap-written fiber
      Bragg gratings (OWFBG's) in the fiber lasers and by cooling of the Er-doped fiber
      with liquid N(2) . Our experiment shows that by utilizing the OWFBG's to select
      the lasing wavelengths one can achieve fiber lasers with lasing wavelengths and
      lasing wavelength separations that match the International Telecommunication
      Union channel-allocation grid well.

PMID- 18066151
TI  - Bragg gratings in ternary SiO(2):SnO(2):Na(2)O optical glass fibers.
AB  - Bragg gratings have been written in an optical fiber with a core made from
      ternary SiO(2): SnO(2): Na(2)O glass and a SiO(2) cladding. The presence of
      Na(2)O allows for higher concentrations of SnO>(2) , which are believed to be
      responsible for the photorefractive response of this composition. In these
      preliminary experiments significant refractive-index modulations, up to 6.2x10(
      4) , have been achieved with a 248-nm excimer laser and a phase mask to write
      gratings for reflectivity at ~1.5microm . The induced refractive-index changes
      show enhanced temperature stability, and there is no sign of any erasure up to
      temperatures exceeding 600 degrees C.

PMID- 18066152
TI  - Temperature dependence of chromatic dispersion in various types of optical fiber.
AB  - The temperature dependence of chromatic dispersion is examined for various types
      of fiber. Its coefficient is found to depend strongly on the dispersion slope.
      Dispersion-flattened fiber has a significantly low coefficient of 
      0.0005(ps/nm/km)/ degrees C , compared with -0.0038(ps/nm/km)/ degrees C for
      large-core nonzero dispersion-shifted fiber. Transmission lines with low
      dispersion slopes consisting of pure silica core fiber and dispersion
      compensating fiber also exhibit low coefficients of less than -0.001(ps/nm/km)/
      degrees C because of their compensating effects.

PMID- 18066153
TI  - Optical image encryption based on multifractional Fourier transforms.
AB  - We propose a new image encryption algorithm based on a generalized fractional
      Fourier transform, to which we refer as a multifractional Fourier transform. We
      encrypt the input image simply by performing the multifractional Fourier
      transform with two keys. Numerical simulation results are given to verify the
      algorithm, and an optical implementation setup is also suggested.

PMID- 18066154
TI  - Quantitative gas sensing by backscatter-absorption measurements of a pseudorandom
      code modulated lambda ~ 8-microm quantum cascade laser.
AB  - We have demonstrated quantitative chemical vapor detection with a multimode
      quantum cascade (QC) laser. Experiments incorporated pseudorandom code (PRC)
      modulation of the laser intensity to permit sensitive absorption measurements of
      isopropanol vapor at 8.0micro . The demonstration shows the practicality of one
      technical approach for implementing low-peak-power QC lasers in the transmitter
      portion of a differential absorption lidar (DIAL) system. With a 31-chip, 300
      ns/chip PRC sequence, the measured isopropanol detection limit was 12 parts in
      10(6) by volume times meters (~3x10(-3) absorption) for a simple backscatter
      absorption measurement configuration.

PMID- 18066155
TI  - Continuous tuning of an electrically tunable external-cavity semiconductor laser.
AB  - We propose and demonstrate a novel approach to achieving rapid and phase-coherent
      continuous broadband tuning of a single-mode external-cavity semiconductor laser.
      Two internal acousto-optic devices control the angle of incident light on a
      diffraction grating and the effective round-trip phase electronically. Although
      the present implementation derives the phase from a long delay line and is not
      yet mode-hop free, the new approach lends itself to fully electronic control.

PMID- 18066156
TI  - All-solid-state high-power conduction-cooled Nd:YLF rod laser.
AB  - A high-average-power conduction-cooled diode-pumped Nd:YLF rod laser has been
      developed. A new conduction-cooled side-pumping scheme with a solid prismatic
      pump-light confinement cavity was employed. A transparent, high-thermal
      conductivity MgF>(2) prism was used as a highly efficient pump cavity as well as
      a low-thermal-resistance heat spreader. The pumping efficiency and thermal
      resistance of the cavity were 85% and 0.20 degrees C degrees W, respectively.
      When this scheme was combined with heat pipes for heat removal, a maximum average
      output power of 72 W was demonstrated, with an optical slope efficiency as high
      as 49%.

PMID- 18066157
TI  - Phase-shift error as a result of molecular alignment distortions in a liquid
      crystal point-diffraction interferometer.
AB  - We report the observation of nematic director distortions around the diffracting
      element of a liquid-crystal point-diffraction interferometer. The observed
      director field distortions are similar to those reported in the literature for
      other liquid-crystal guest-host systems. We show how the alignment distortion
      changes as a function of the voltage applied to the liquid-crystal cell, leading
      to an observed phase-shift error. Tailoring of surface anchoring conditions and
      judicious choice of phase-shift algorithm can improve device accuracy.

PMID- 18066158
TI  - Tomographic imaging by two-wave mixing with a wavelength-scanning laser diode.
AB  - A method of tomographic imaging is proposed in which two-wave mixing in a
      photorefractive crystal is used with wavelength scanning of a laser diode and
      phase modulation of the pump beam. This method provides full optical processing
      and is effective for weak light from objects because of the use of two-wave
      mixing. The depth resolution of the method was ~1 cm when the wavelength-scanning
      width was ~0.02 nm .

PMID- 18066159
TI  - Suppression of radiation in a momentum-nonconserving nonlinear interaction.
AB  - We have considered the quadratic nonlinear radiation from a thin dipole sheet in
      front of a mirror. Radiation at the second-harmonic (SH) frequency on incidence
      of a fundamental field can be inhibited or enhanced independently of the SH field
      intensity stored between the nonlinear layer and the mirror. We have shown that
      this apparent contradiction can be fully understood only if the quadratic
      nonlinear interaction includes terms with a momentum mismatch equal to the
      magnitude of the SH field wave vector, such as the term that accounts for
      transfer of energy from the reflected SH field back to the incident fundamental.

PMID- 18066160
TI  - High-dynamic-range cascaded-focus optical limiter.
AB  - We report experimental results of using an f/5 , cascaded-focus optical geometry
      for a high-dynamic-range optical limiter. The device consists of a 2-cm-thick
      CS(2) cell at the first focus and a reverse saturable-absorber dye in a thin cell
      (0.1 mm) at the second focus. The strong self-focusing in the CS(2) that is due
      to the ac Kerr effect and electrostriction keeps the energy at the second cell
      below its damage threshold. Using lead phthalocyanine in chloroform as the
      reverse saturable-absorption material, we clamped the maximum output energy below
      1muJ for input energies up to 14.5 mJ without damage. We used a frequency
      doubled, Q -switched 5-ns (FWHM) Nd:YAG laser operating at a 10-Hz repetition
      rate. The measured dynamic range of the device is at least 7500.

PMID- 18066161
TI  - Fundamental limits on third-order molecular susceptibilities.
AB  - By the use of sum rules, the largest third-order molecular nonlinear-optical
      susceptibilities allowed by quantum mechanics are determined. The theoretical
      upper limit is found to depend only on the first excited-state transition energy
      and on the number of electrons, in agreement with experimental data.

PMID- 18066162
TI  - Determining the dispersions of the fifth- and seventh-order nonlinear optical
      susceptibilities of a poly(4-BCMU) film through electroabsorption spectroscopy.
AB  - The dispersions of the fifth- and seventh-order nonlinear optical
      susceptibilities, chi((5))(113333) and chi((7))(11333333) , respectively, of a
      polydiacetylene film, poly(4-BCMU), are determined through electroabsorption
      spectroscopy. To our knowledge this is the first time that a spectrum of seventh
      order nonlinear optical susceptibility has been obtained by means of electro
      optic measurements.

PMID- 18066163
TI  - Nondestructive evaluation of incipient corrosion in a metal beneath paint by
      second-harmonic tomography.
AB  - A second-harmonic optical scanning imaging method for nondestructive evaluation
      of corrosion of painted metals is demonstrated. Two-dimensional images of the
      sectional structure from a sample of painted metal with corrosion were obtained
      by detection of second-harmonic generation (SHG). The second-harmonic signals
      generated from paint, corrosion, and metal can be spatially imaged in ~10-mum
      sliced subsurface layers. Corroded metal layers covered with paint are found to
      have more intensity variation than normal polished metal. The spatial mapping of
      the second-harmonic signals shows depth differentiation of paint, corrosion, and
      metal surfaces. The depth of corrosion beneath the paint can be measured from the
      SHG images.

PMID- 18066164
TI  - Measurement of the thermal contribution to the nonlinear refractive index of air
      at 1064nm.
AB  - The thermal contribution to the nonlinear refractive index of air at 1.064mum was
      measured with a high-finesse Fabry-Perot cavity and a 500-mW cw laser beam. At
      room temperature and pressure, the nonlinear refractive-index coefficient of air
      was found to be n(2)((th))=(-1.9+/-0.2)x10 (-14) cm(2)/W for a beam waist radius
      of 0.23 mm and was found to be independent of the relative humidity. The thermal
      nonlinearities of N(2) , O(2) , and CO(2) were also measured, and it was found
      that the dominant contribution to air is its O(2) content.

PMID- 18066165
TI  - Hybrid correlator employing a chirp-encoded binary phase-only filter.
AB  - A novel correlator architecture is described that is similar to the VanderLugt
      correlator (VLC) but differs because the input Fourier transform (FT) is
      performed electronically rather than optically. We present results in which the
      FT's are reduced to binary phase-only filters (BPOF's); the required
      multiplication of the input and the reference FT's (performed optically in the
      VLC) is performed electronically simply by use of a single XOR logic gate. The
      problematic zero order and symmetric correlation peak are shown to be removed by
      use of a chirp-encoded BPOF.

PMID- 18066166
TI  - Noise equalization in Stokes parameter images obtained by use of variable
      retardance polarimeters.
AB  - An imaging variable retardance polarimeter was developed and tested by Tyo and
      Turner [Proc. SPIE 3753, 214 (1999)]. The signal-to-noise ratio (SNR) in the
      reconstructed polarization images obtained with this system varied for the four
      Stokes parameters. The difference in SNR is determined to be due to differences
      in the Euclidean lengths of the rows of the synthesis matrix used to reconstruct
      the Stokes parameters from the measured intensity data. I equalize (and minimize)
      the lengths of the rows of this matrix by minimizing the condition number of the
      synthesis matrix, thereby maximizing the relative importance of each of the
      polarimeter measurements. The performance of the optimized system is demonstrated
      with simulated data, and the SNR is shown to increase from a worst case of -3.1
      dB for the original settings to a worst case of +5.0 dB for the optimized system.

PMID- 18066167
TI  - Remote detection of Raman scattering by use of a holographic optical element as a
      dispersive telescope.
AB  - We describe the retrieval of nighttime lidar profiles by use of a large
      holographic optical element to simultaneously collect and spectrally disperse
      Raman-shifted return signals. Results obtained with a 20-Hz, 6-mJ/pulse ,
      frequency-tripled Nd:YAG source demonstrate profiles for atmospheric nitrogen
      with a range greater than 1 km for a time average of 26 s.

PMID- 18066168
TI  - Phase matching in nonlinear chi((2)) photonic crystals.
AB  - We analyze harmonic generation in a two-dimensional (2D) chi((2)) photonic
      crystal and demonstrate the possibility of multiple phase matching and multicolor
      parametric frequency conversion. We suggest a new type of photonic structure to
      achieve simultaneous generation of several harmonics; we also present both
      general analytical results and design parameters for 2D periodically poled
      LiNbO(3) structures.

PMID- 18066169
TI  - Comment on "Time reversal of ultrafast waveforms by wave mixing of spectrally
      decomposed waves".
AB  - In a recent Letter [Opt. Lett. 25, 132 (2000)] the properties of two different
      techniques for time reversal of ultrafast optical waveforms were compared.
      Although both techniques, spectral phase conjugation and spectral inversion,
      perform the same function for real pulses, for pulses with complex envelope
      functions it was asserted that only spectral inversion gives true time reversal.
      I argue here for a different interpretation.

PMID- 18066170
TI  - Reply to "Comment on 'Time reversal of ultrafast waveforms by wave mixing
      spectrally decomposed waves'".
AB  - In response to a comment on our Letter [Opt. Lett. 25, 132 (2000)], we reiterate
      the distinction between the spectral inversion and the spectral phase conjugation
      processing techniques. The former achieves time reversal of the complex amplitude
      waveform, whereas the latter performs time reversal of the real electric field.

PMID- 18066171
TI  - Intense terahertz pulses by four-wave rectification in air.
AB  - We describe a new four-wave rectification method for the generation of intense,
      ultrafast terahertz (THz) pulses from gases. The fundamental and second-harmonic
      output of an amplified Ti:sapphire laser is focused to a peak intensity of
      ~5x10(14)W/cm (2) . Under these conditions, peak THz fields estimated at 2 kV/cm
      have been observed; the measured power spectrum peaks near 2 THz. Phase-dependent
      measurements show that this is a coherent process and is sensitive to the
      relative phases of the fundamental and second-harmonic pulses. Comparable THz
      signals have been observed from nitrogen and argon as well as from air.

PMID- 18066172
TI  - Time-decorrelated multifocal array for multiphoton microscopy and micromachining.
AB  - We demonstrate a temporally decorrelated, multifocal multiphoton microscope.
      Using an etalon, we split the 800-nm light from either an ultrashort-pulsed Ti:Al
      (2)O (3) oscillator or a Ti:Al (2)O (3) regenerative amplifier into an array of
      beamlets that are delayed with respect to one another in time. The collimated
      beams overlap at slightly different input angles at the entrance pupil of a 1.25
      numerical aperture oil-immersion objective to produce an array of foci that are
      temporally decorrelated at the focal plane of the objective. The temporal
      decorrelation eliminates any interference among the foci and permits multifocal
      multiphoton imaging with the resolution of single-point illumination.

PMID- 18066174
TI  - Particle counting in the presence of a dominant background by incoherent
      statistical optics.
AB  - Extraction of the mean number of foreground particles that evolve in the presence
      of an arbitrary background population is achieved by means of a comparative
      measurement of incoherent scattered intensity fluctuations. Photon-counting
      experiments are conducted on test particles (latex spheres) that appear in a
      background population of polydisperse sand particles (Arizona fine, International
      Organization for Standardization standard 12103). Measurements show recovery of
      the test particle concentration with an error of less than 10%, despite the
      presence of the background population that contributes more than 90% of the
      scattered intensity.

PMID- 18066173
TI  - Convergence test for inversion of frequency-resolved optical gating spectrograms.
AB  - We describe a new and simple method to aid in the analysis of retrieved pulses
      from inverted frequency-resolved optical gating (FROG) traces. The analysis can
      separate noise from distortion and shows that distortion is more deleterious to
      the retrieved pulse than is pure noise. The analysis relies on the fact that FROG
      traces can be constructed from a single outer product of two vectors, whereas
      distortion and noise require the sum of a series of outer products.

PMID- 18066175
TI  - 2-microm Doppler lidar transmitter with high frequency stability and low chirp.
AB  - A coherent Doppler lidar system was frequency stabilized in a master-slave
      configuration by a phase-modulation technique. The short-term frequency
      stability, ~0.2 MHz rms, was maintained in a vibrational environment on a ship
      during a field campaign in the tropical Pacific Ocean. The long-term frequency
      stability was <2.6 kHz/h. Thus, in many applications, shot-to-shot frequency
      correction can be disregarded, which will result in increased speed and
      simplicity of the data-acquisition system. A frequency chirp could not be
      detected. These properties permit Doppler wind measurements with high efficiency
      and duty cycles to be made, even on airborne and spaceborne platforms.

PMID- 18066176
TI  - Wind measurements with 355-nm molecular Doppler lidar.
AB  - A Doppler lidar system based on the molecular double-edge technique is described.
      The system is mounted in a modified van to permit deployment in field operations.
      The lidar operates with a tripled Nd:YAG laser at 355 nm, a 45-cm-aperture
      telescope, and a matching azimuth-over-elevation scanner to permit full sky
      access. Validated atmospheric wind profiles were measured from 1.8 to 35 km with
      a 178-m vertical resolution. The range-dependent rms deviation of the horizontal
      wind speed is 0.4-6 m/s. The measured wind speed and direction are in good
      agreement with the rawinsonde wind measurements made simultaneously from the same
      location.

PMID- 18066177
TI  - Optical carrier Brillouin processing of microwave photonic signals.
AB  - We introduce a novel concept in Brillouin signal processing based on modification
      of the optical carrier's magnitude and phase by stimulated Brillouin scattering
      induced depletion. The technique offers wideband processing and low noise and
      requires only low optical power. Application to the enhancement of a 25-km high
      frequency analog link is experimentally demonstrated and yields a 6.5-GHz
      bandwidth extension and a 13-dB reduction in the link insertion loss without
      intermodulation distortion.

PMID- 18066178
TI  - Ordered bundles of infrared-transmitting AgClBr fibers: optical characterization
      of individual fibers.
AB  - Silver halide (AgCl(x) Br(1-x)) crystals were extruded to form polycrystalline
      fibers that are highly transparent in the spectral range 3-30 mum. Ordered
      bundles consisting of as many as 9000 fibers were fabricated by multiple
      extrusion steps. The transmission loss of an individual fiber in the 100-fiber
      bundles was 0.12 dB/cm, and the cross talk between neighboring fibers in the 900
      fiber bundles was 25%. Thermal images of bodies at room temperature have been
      transmitted through the bundles. Such ordered bundles provide a solution for the
      problem of thermal imaging in regions where there is no line of sight between a
      thermal camera and a warm object.

PMID- 18066179
TI  - Autosoliton transmission in dispersion-managed systems guided by in-line
      nonlinear optical loop mirrors.
AB  - We examine the feasibility of optical pulse transmission in dispersion-managed
      fiber systems with in-line nonlinear optical loop mirrors. Applying numerical
      analysis, we find regimes of stable propagation over long distances in such
      lines, with a significant increase in the signal-to-noise ratio.

PMID- 18066180
TI  - Diffraction efficiency of localized holograms in doubly doped LiNbO(3) crystals.
AB  - The diffraction efficiency of M holograms superimposed in the volume of the
      recording medium is proportional to 1/M(2). We present a method, based on
      nondestructive localized holograms in a doubly doped LiNbO(3) crystal, that
      allows us to also record M holograms in the same volume without an exposure
      schedule or a diffraction efficiency that has 1/M dependence. We compare
      experimentally the final diffraction efficiency obtained with the localized and
      distributed recording methods.

PMID- 18066181
TI  - Diode laser extended cavity for broad-range fast ramping.
AB  - A novel design for an extended-cavity diode laser is presented. The cavity
      contains an electro-optic prism for synchronous tuning of the cavity length and
      the grating's incident angle. A simple analysis of the cavity is presented.
      Experimental results are reported that show mode-hop-free tuning over more than
      10 GHz with high linearity and reproducibility. To the authors' knowledge, this
      is the first demonstration of mode-hop-free tuning of an extended cavity over
      several free spectral intervals with an electro-optic crystal.

PMID- 18066182
TI  - Magneto-optic parametric oscillation.
AB  - We develop a model of large-signal steady-state magneto-optic parametric
      oscillation in the Faraday configuration of a singly resonant cavity. The
      conversion efficiency and the threshold and phase-matching conditions are
      discussed, and we show that tunable phase matching can be achieved by use of a
      static magnetic field, eliminating any walk-off effects.

PMID- 18066183
TI  - Efficient second-harmonic generation at 384 nm in periodically poled lithium
      tantalate by use of a visible Yb--Er-seeded fiber source.
AB  - We generated 56 mW of average power at 384 nm in periodically poled lithium
      tantalate by use of a visible fiber source based on a variable-pulse format
      seeded Yb-Er amplifier and frequency upconversion in periodically poled KTP. The
      feasibility of high-average-power, wide ultraviolet wavelength-range fiber-based
      sources is evaluated.

PMID- 18066184
TI  - Polymer-based microcavity with photoencoded quadratic nonlinearity.
AB  - Functional electro-optic polymer thin films embedded in microcavity structures
      have been poled by an all-optical procedure based on the interference of
      multiphoton absorption processes. The photoinduced X((2)) tensor was then further
      addressed at modal resonance for the fundamental wavelength, leading to
      significant enhancement of the second-harmonic-generation efficiency. An order-of
      magnitude enhancement, which is due to electric field resonant conditions inside
      the microcavity, has been probed by an optical parametric oscillator, in
      comparison with a single-path thin-film configuration. This configuration opens
      new perspectives in the realm of nonlinear photonic device processing.

PMID- 18066185
TI  - Spatial redistribution of energy in a nanosecond laser pulse by an organic
      optical limiter.
AB  - The spatial redistribution of energy resulting from the interaction between a
      near-diffraction-limited nanosecond laser pulse and the nonlinear absorbing
      optical limiting dye silicon naphthalocyanine is described, for what is to our
      knowledge the first time, in an optical geometry that is likely to be found in
      practical applications. For input fluences above that required for nonlinear
      absorption but below that for bubble growth, a plane wave or Gaussian spatial
      input evolves unexpectedly to a sharp central spike and a well-defined outer
      ring. The observed energy redistribution is thought to rely on a combination of
      nonlinear processes, since a pure absorptive process alone cannot explain the
      profiles presented. A model involving nonlinear absorption and nonlinear
      refraction qualitatively reproduces the observed spatial profiles. It is clear
      from the results that the performance of optical limiting dyes in representative
      optical geometries, even at fluences well below that required for bubble growth,
      cannot be described solely by nonlinear absorption.

PMID- 18066186
TI  - Fast photorefractive response in B(12)SiO(20) in the near infrared.
AB  - The polarization self-modulation effect was applied for effective measurement of
      the characteristic response time of nominally pure Bi(12)SiO(20) (BSO) at
      wavelengths of 810 and 980 nm. Owing to oxygen deficiency in the crystal lattice,
      the BSO crystals showed unusual photorefractive sensitivity and remarkable
      operation speed in the near-infrared spectral region. A response time of 130 ms
      was measured at 810 nm, and a response time of 540 ms was measured at 980 nm,
      with incident intensities of 110 and 200mW/cm(2), respectively. To our knowledge,
      this is the first experimental evidence of a subsecond response in the infrared
      for a nonsemiconductor photorefractive material.

PMID- 18066187
TI  - Stable, continuously tunable operation of a diode-pumped doubly resonant optical
      parametric oscillator.
AB  - We demonstrate, for what is the first time to our knowledge, long-term stable,
      continuously tunable operation of a doubly resonant optical parametric oscillator
      (OPO) pumped by a single-stripe diode laser without the use of an external
      semiconductor amplifier. The OPO is based on periodically poled lithium niobate
      and is pumped by a 150-mW distributed Bragg grating diode laser. 18-mW total
      output power is generated at 1.3- and 2.3-mum wavelengths. A cavity-length servo
      system allows continuous signal tuning of 17 GHz and idler tuning of 10 GHz,
      limited only by the range of a piezoelectric cavity mirror mount. OPO tuning is
      demonstrated from 1.1 to 1.4 mum and from 2.2 to 3.7 mum.

PMID- 18066188
TI  - Tunable phase conjugation by intracavity degenerate four-wave mixing in an
      injection-seeded solid dye laser.
AB  - We demonstrate efficient degenerate four-wave mixing in a laser injection-seeded
      solid dye laser. Phase-conjugate energy of as much as 140 times the total energy
      injected externally into the phase conjugator was extracted. Moreover, efficient
      phase-conjugate energy was obtained in the broad wavelength region from 558 to
      567 nm.

PMID- 18066189
TI  - Nonlinear propagation of subpicosecond ultraviolet laser pulses in air.
AB  - We report filamentation of subpicosecond UV laser pulses with only millijoule
      energy in atmosphere. The results are in good agreement with a numerical
      simulation using a quasi-three-dimensional propagation code.

PMID- 18066190
TI  - Engineerable generation of quadratic solitons in synthetic phase matching.
AB  - We show that the efficiency and the mismatch bandwidth of quadratic soliton
      formation under conditions of second-harmonic generation can be enhanced in an
      important way in synthetic phase-matching profiles. Soliton excitation in smooth
      but arbitrary profiles is shown to be well described by a reduced variational
      approach. The potential of abrupt, nonadiabatic profiles for improved soliton
      formation is numerically revealed.

PMID- 18066191
TI  - Demonstration of highly efficient photon echoes.
AB  - Highly efficient two-pulse and stimulated photon echoes are experimentally
      demonstrated in an absorbing medium. Recall efficiencies of 235% and 150% with
      excellent signal contrast are measured for two-pulse and stimulated photon
      echoes, respectively, in a Tm:YAG crystal with an absorption length of 3.8. The
      reported efficiencies do not include any correction for decay or beam profile. We
      believe that this is the first demonstration of an uncorrected echo efficiency
      greater than 100% with good signal fidelity in an optically thick medium.

PMID- 18066192
TI  - High-density speed optical near-field recording reading with a pyramidal silicon
      probe on a contact slider.
AB  - We demonstrate high-density-speed phase-change recording-reading by use of a
      pyramidal silicon structure. The contact slider, which has a pyramidal silicon
      probe array with height dispersion of less than 10 nm, is fabricated by use of a
      silicon-on-insulator wafer. By illumination with a laser beam (lambda = 830 nm)
      of one element of the probe array, we find the shortest phase-change mark length
      and the carrier-to-noise ratio to be 110 nm and 10 dB, respectively,
      corresponding to a data transmission rate of 2.0 MHz. This rate can be increased
      to 200 MHz by use of all elements of the probe array.

PMID- 18066193
TI  - Toward soliton emission in asymmetric GaAs/AlGaAs multiple-quantum-well waveguide
      structures below the half-bandgap.
AB  - We report what is to our knowledge the first experimental evidence of nonlinear
      beam displacement in a strip-loaded GaAs/AlGaAs multiple-quantum-well waveguide
      with an asymmetric, nonlinear cladding. An intensity-dependent spatial
      displacement of ~2 mum was observed for the guided mode at a wavelength of 1.55
      mum. Numerical simulations that correspond to the experiment are also presented.
      The device has the potential of providing a soliton-emission-based, ultrafast all
      optical switch.

PMID- 18066194
TI  - Massively parallel low-cost pick-and-place of optoelectronic devices by
      electrochemical fluidic processing.
AB  - We describe a novel electrochemical technique for the nonlithographic, fluidic
      pick-and-place assembly of optoelectronic devices by electrical and optical
      addressing. An electrochemical cell was developed that consists of indium tin
      oxide (ITO) and n -type silicon substrates as the two electrode materials and
      deionized water (R = 18 MOmega) as the electrolytic medium between the two
      electrodes. 0.8-20-microm-diameter negatively charged polystyrene beads, 50-100
      microm-diameter SiO(2) pucks, and 50-microm LED's were successfully integrated
      upon a patterned silicon substrate by electrical addressing. In addition, 0.8
      microm-diameter beads were integrated upon a homogeneous silicon substrate by
      optical addressing. This method can be applied to massively parallel assembly
      (>1000 x 1000 arrays) of multiple types of devices (of a wide size range) with
      very fast (a few seconds) and accurate positioning.

PMID- 18066195
TI  - Efficient method for evaluation of the diffraction efficiency upper bound of
      diffractive phase elements.
AB  - The theoretical diffraction efficiency upper limit of diffractive phase elements
      (DPE's) with finite apertures is investigated. A successful numerical method of
      evaluating the efficiency upper bound of DPE's is proposed. The method includes a
      hybrid optimization procedure that combines a genetic algorithm with the
      conjugate gradient method. This efficient global optimization technique can also
      be used to design DPE's. Simulation computations are detailed for rotationally
      symmetric beam shaping in which a Gaussian profile laser beam is converted into a
      uniform beam. Numerical results demonstrate that the estimated diffraction
      efficiency upper bound is consistent with the design results.

PMID- 18066196
TI  - Use of the van Cittert-Zernike theorem for partially polarized sources.
AB  - We introduce an extension of the van Cittert-Zernike theorem to spatially
      incoherent sources with partial polarization. We show through a simple example
      that fields generated by such sources can possess correlation matrices with
      interesting properties. In particular, we show that by suitable modulation of the
      polarization state across the incoherent source, the correlation between the
      orthogonal components of the field as well as the degree of polarization may
      drastically change on propagation.

PMID- 18066197
TI  - Photon antibunching in the fluorescence of individual color centers in diamond.
AB  - We observed photon antibunching in the fluorescent light emitted from a single
      nitrogen-vacancy center in diamond at room temperature. The possibility of
      generating triggerable single photons with such a solid-state system is
      discussed.

PMID- 18066198
TI  - Demonstration of highly efficient waveguiding in a photonic crystal slab at the
      1.5-microm wavelength.
AB  - Highly efficient transmission of 1.5-microm light in a two-dimensional (2D)
      photonic crystal slab waveguide is experimentally demonstrated. Light waves are
      shown to be guided along a triple-line defect formed within a 2D crystal and
      vertically by a strong index-guiding mechanism. At certain wavelength ranges,
      complete transmission is observed, suggesting lossless guiding along this
      photonic one-dimensional conduction channel.

PMID- 18066199
TI  - Robust polymer colloidal crystal photonic bandgap structures.
AB  - New polymeric matrices are presented that embed organic colloidal crystalline
      arrays (CCA's) into mechanically stable photonic bandgap structures. We achieved
      these new matrices either by dispersing polystyrene CCA's with high molecular
      weight hydrophilic polymer [poly(ethylene glycol); (PEG)] or through in situ
      polymerization of hydrophilic monomers (acrylamide and acrylate functional PEG
      variants) about the CCA. CCA-dispersed PEG matrices exhibited strong red
      opalescence with a narrow peak at 614 nm and were sufficiently rigid to withstand
      repeated mechanical deformation. Visible photonic bandgaps also were observed
      from free-standing CCA composites with cross-linked poly(N, N-dimethylacrylamide)
      matrices. The results demonstrate the technological potential for robust organic
      photonic crystals.

PMID- 18066200
TI  - Detection of corrosion beneath a paint layer by use of spectral polarization
      optical imaging.
AB  - The spectral and polarization properties of scattered light were used to image
      corrosion beneath the surface of a painted aluminum plate. The quality of imaging
      of the corrosion on the metal surface was significantly enhanced by the spectral
      polarization optical imaging technique. Depolarization scattered light was used
      to detect and image corrosion beneath the paint layer.

PMID- 18066201
TI  - Wigner representation of Laguerre--Gaussian beams.
AB  - A phase-space description of the Laguerre-Gaussian modes is presented that points
      out the connection between these modes and the Hermite-Gaussian modes. We exploit
      the underlying phase-space symmetries to derive a closed-form expression for the
      Wigner distribution function of Laguerre-Gaussian modes. This expression is as
      compact as the one for the Hermite-Gaussian modes.

PMID- 18066202
TI  - Fresnel diffraction on the edge of causality.
AB  - Taking advantage of the slow optical response of low-temperature rare earth ion
      doped crystal, we explore the similarity between causality and Fresnel
      diffraction by a straight edge. We relate these features to spectral resolution
      and selectivity. The concept is illustrated with experimental data.

PMID- 18066203
TI  - Acoustic-induced switching of the reflection wavelength in a fiber Bragg grating.
AB  - Coupling between copropagating core and cladding modes was implemented by
      acoustic generation of lateral vibration of an etched fiber. When these coupling
      processes were combined with counterpropagating coupling of a core mode and a
      cladding mode and the Bragg reflection of a fiber grating, switching of
      reflection wavelength between the Bragg wavelength and cladding-mode coupling
      wavelengths was achieved. We report the implementation of such acoustically
      induced switching behaviors and explain their operation principles. The
      implemented results can be used for wavelength-division multiplexed add-drop
      filtering.

PMID- 18066204
TI  - Statistical characterization of fiber random birefringence.
AB  - The statistical properties of the random birefringence that affects long single
      mode fibers are experimentally evaluated by means of a polarization-sensitive
      optical time-domain reflectometry. The measurements are in good agreement with
      theoretical predictions and show, for what we believe is the first time, that the
      components of the local birefringence vector are Gaussian random variables.

PMID- 18066205
TI  - Highly birefringent photonic crystal fibers.
AB  - We report a strongly anisotropic photonic crystal fiber. Twofold rotational
      symmetry was introduced into a single-mode fiber structure by creation of a
      regular array of airholes of two sizes disposed about a pure-silica core. Based
      on spectral measurements of the polarization mode beating, we estimate that the
      fiber has a beat length of approximately 0.4 mm at a wavelength of 1540 nm, in
      good agreement with the results of modeling.

PMID- 18066206
TI  - Donor and acceptor guided modes in photonic crystal fibers.
AB  - We present a triangular photonic-crystal-fiber structure that exhibits guided
      modes simultaneously above and below the first conduction band. We achieve this
      configuration by decreasing the size of one of the airholes (the defect) in a
      specific triangular lattice. More generally, we analyze the behavior of guided
      modes that depends on the size of the defect. Defects generated by decreasing or
      increasing the size of one of the holes produce donor or acceptor guided modes,
      respectively, in analogy with impurity levels in solid-state crystals. We
      conclude that the guiding mechanism for both donor and acceptor modes is produced
      by a unique phenomenon of multiple interference by a periodic structure.

PMID- 18066207
TI  - Brillouin-based fiber-optic distributed temperature sensor with optical
      preamplification.
AB  - Optical preamplification has been used in a fiber-optic distributed temperature
      sensor based on spontaneous Brillouin scattering and the use of direct detection,
      resulting in improved signal-to-noise ratios. The fiber-based optical
      preamplifier system comprises a three-port circulator, an erbium-doped fiber
      amplifier with a small-signal gain of 27 dB, and a fiber Bragg grating with 47
      GHz bandwidth. An improvement of 17 dB in the optical signal-to-noise ratio for
      the Brillouin signal is demonstrated in a 23-km sensor. The limit to the signal
      to-noise ratio is attributed to spontaneous-spontaneous beat noise generated at
      the photodetector by amplified spontaneous emission from the optical amplifier.

PMID- 18066208
TI  - Fiber-optic polarimetric strain sensor with three-wavelength digital phase
      demodulation.
AB  - A fiber-optic polarimetric strain sensor of l(S)=10-cm sensing length with three
      wavelength passive quadrature digital phase demodulation is investigated. The
      demodulation unit uses a superluminescent diode light source with narrow-band
      interference filters in front of the photodiodes and real-time processing of the
      interference intensities by an arctan-phase-stepping algorithm. Quasi-static
      strain sensing is performed during slow periodic compression of a composite
      reinforced plastic rod with a sensor glued to its surface. The measured
      displacement sensitivity of delta?/deltal=125 mrad/mum, with a resistive strain
      gauge as a reference, agrees well with the value of 119 mrad/mum previously
      determined by fringe-distance measurement [Bock et al., Pure Appl. Opt. 5, 125
      (1996)]. Despite a coherence-limited fringe contrast of only a few percent, a
      linearity of the phase-strain characteristic of the order of 1% and a strain
      resolution of 2.5muepsilon are demonstrated.

PMID- 18066209
TI  - Angle-multiplexed hologram storage in LiNbO(3):Tb, Fe.
AB  - We have performed hologram multiplexing with a cw laser at lambda=532 nm in a
      near-stoichiometric LiNbO(3) :Tb, Fe crystal that exhibits a visible absorption
      band induced by UV light. When 50 plane-wave holograms were angle multiplexed
      from the UV preexposed state, the recording sensitivity gradually decreased,
      owing to bleaching of the induced absorption. However, a conventional recording
      schedule of multiplexing many holograms of equal diffraction efficiency can be
      used in this photochromic material. The gradual decrease in recording sensitivity
      throughout multiplexing can be compensated for by the increased erasure-time
      constants of later-written holograms. An M/# of 1.73 was obtained in a crystal of
      3.3-mm thickness.

PMID- 18066210
TI  - Temperature and flow-velocity measurements by use of laser-induced
      electrostrictive gratings.
AB  - Light scattering from laser-induced electrostrictive gratings has been used for
      simultaneous, instantaneous, nonintrusive, and remote measurements of temperature
      and velocity in a submerged air jet. We accomplished phase-sensitive detection of
      scattered light by superimposing two signal beams whose frequencies were Doppler
      shifted by the movement of the grating. Temperatures in the range 295-600 K and
      flow velocities in the range 10-100 m/s were measured.

PMID- 18066211
TI  - Efficient blue cw Nd:YAG microchip laser with two intracavity frequency doublers.
AB  - A microchip cavity including a half-monolithic Nd:YAG- KNbO(3) chip and a second
      KNbO(3) crystal is presented. An output power of up to 30 mW at 473 nm pumped by
      a single stripe 1-W at 808-nm diode is achieved. The laser can be operated in
      either single-longitudinal or multilongitudinal mode by rotation of the second
      frequency-doubling crystal to 0 degrees or 90 degrees from the first one. The cw
      output noise is less than 2% for both cases.

PMID- 18066212
TI  - Multiwatt continuous-wave adaptive laser resonator.
AB  - We present, for what we believe is the first time, results of continuous-wave
      diode-pumping of a Nd:YVO (4) laser with an adaptive gain-grating resonator. The
      system is shown to produce more than a 7-W output in a TEM>(00) single
      longitudinal mode with a laser beam propagation parameter M(2) of <1.3 and <1.1
      in the x and y axes, respectively. We demonstrate the self-adaptive abilities of
      the resonator by spatial correction of an intracavity aberrator for both injected
      and self-starting versions of the cavity.

PMID- 18066213
TI  - Fabrication and optimization of uniform output couplers for far-infrared lasers.
AB  - An improved technique for the fabrication of uniform output couplers for far
      infrared lasers has been developed. The technique includes a process for
      uniformly removing material from the back side of the coupler's substrate to tune
      the coupler's reflectivity precisely to the specified value for a particular
      laser line. Depending on the condition of the coupler after use, it can be
      retuned to another laser line, which lies within the coupler's reflectance
      envelope. Furthermore, when there is the possibility of lasing at two different
      laser wavelengths (as happens with some far-infrared lasers), it is possible to
      optimize the coupler for one wavelength while at the same time detuning the other
      wavelength. The fabrication and optimization of these devices are discussed.

PMID- 18066214
TI  - Frequency-narrowed external-cavity diode-laser-array bar.
AB  - We demonstrate that appropriately designed external cavities can be used to
      frequency narrow high-power diode-array bars. Using a commercial 20-W array, we
      narrow the linewidth to 50 GHz with 14 W of cw output power. A magnifying
      telescope and a cylindrical collimating lens minimize broadening owing to
      curvature in the alignment of the diode-array elements.

PMID- 18066215
TI  - High-speed fiber based polarization-sensitive optical coherence tomography of in
      vivo human skin.
AB  - A high-speed single-mode fiber-based polarization-sensitive optical coherence
      tomography (PS OCT) system was developed. With a polarization modulator, Stokes
      parameters of reflected flight for four input polarization states are measured as
      a function of depth. A phase modulator in the reference arm of a Michelson
      interferometer permits independent control of the axial scan rate and carrier
      frequency. In vivo PS OCT images of human skin are presented, showing subsurface
      structures that are not discernible in conventional OCT images. A phase
      retardation image in tissue is calculated based on the reflected Stokes
      parameters of the four input polarization states.

PMID- 18066216
TI  - Doppler standard deviation imaging for clinical monitoring of in vivo human skin
      blood flow.
AB  - We used a novel phase-resolved optical Doppler tomographic (ODT) technique with
      very high flow-velocity sensitivity (10microm/s) and high spatial resolution
      (10microm) to image blood flow in port-wine stain (PWS) birthmarks in human skin.
      In addition to the regular ODT velocity and structural images, we use the
      variance of blood flow velocity to map the PWS vessels. Our device combines ODT
      and therapeutic systems such that PWS blood flow can be monitored in situ before
      and after laser treatment. To the authors' knowledge this is the first clinical
      application of ODT to provide a fast semiquantitative evaluation of the efficacy
      of PWS laser therapy in situ and in real time.

PMID- 18066217
TI  - Whole-field optically sectioned fluorescence lifetime imaging.
AB  - We describe a novel three-dimensional fluorescence lifetime imaging microscope
      that exploits structured illumination to achieve whole-field sectioned
      fluorescence lifetime images with a spatial resolution of a few micrometers.

PMID- 18066218
TI  - Coherence-controlled transparency and far-from-degenerate parametric gain in a
      strongly absorbing Doppler-broadened medium.
AB  - An inversionless gain of anti-Stokes radiation above the oscillation threshold in
      an optically dense far-from-degenerate double- ? Doppler-broadened medium
      accompanied by Stokes gain is predicted. The outcomes are illustrated with
      numerical simulations applied to sodium dimer vapor. Optical switching from
      absorption to gain via transparency controlled by a small variation of the medium
      and of the driving radiation parameters, which are at a level of less than one
      photon per molecule, is shown.

PMID- 18066219
TI  - Stable 120-mW green output tunable over 2 THz by a second-harmonic generation
      process in a KTP crystal at room temperature.
AB  - We report on 120-mW directly measured cw power at 532 nm from a tunable alpha 
      distributed-feedback laser diode near 1.064 microm frequency doubled in a KTP
      crystal operating room temperature inside a ring cavity. Our experimental setup
      allows us to scan frequencies up to 2 THz in the green-light domain and thus is
      extremely useful for iodine spectroscopy. We show good agreement between
      experimental results and theoretical predictions for the second-harmonic
      generation process.

PMID- 18066220
TI  - Quasi phase matching in GaAs--AlAs superlattice waveguides through bandgap tuning
      by use of quantum-well intermixing.
AB  - We report the observation of second-harmonic generation by type I quasi phase
      matching in a GaAs-AlAs superlattice waveguide. Quasi phase matching was achieved
      through modulation of the nonlinear coefficient chi((2))(zxy), which we realized
      by periodically tuning the superlattice bandgap. Second-harmonic generation was
      demonstrated for fundamental wavelengths from 1480 to 1520 nm, from the third
      order gratings with periods from 10.5 to 12.4microm . The second-harmonic signal
      spectra demonstrated narrowing owing to the finite bandwidth of the quasi-phase
      matching grating. An average power of ~110 nW was obtained for the second
      harmonic by use of an average launched pump power of ?2.3mW .

PMID- 18066221
TI  - Efficient energy conversion for cubic third-harmonic generation that is phase
      matched in KTiOPO(4).
AB  - We demonstrate, for the first time to our knowledge, that efficient third
      harmonic generation can be achieved with a cubic contribution much larger than
      the quadratic processes. An energy-conversion efficiency of 2.4% is achieved for
      cubic third-harmonic generation that is phase matched along the x axis of a
      KTiOPO(4) crystal by use of a picosecond fundamental laser emitting at 1618 nm.
      The associated cascading processes are only 10% of the pure cubic interaction,
      which is very suitable for study of the specific quantum optical correlations.
      Calculations of the third-harmonic generation conversion efficiency with respect
      to group-velocity dispersion and to the longitudinal Gaussian beam profile
      account well for our experimental results.

PMID- 18066222
TI  - Noncollinear Maker's fringe measurements of second-order nonlinear optical
      layers.
AB  - A novel technique for characterizing thin-film second-order nonlinearities with
      submicrometer resolution for the film's depth is proposed. This method is
      substantially a variation of the classic one-beam Maker's fringe technique and
      uses the second harmonic generated by two noncollinear fundamental beams.
      Compared with that for the one-beam case, this configuration reduces the
      coherence length of the process, thus increasing the resolution for the nonlinear
      depth measurements. The technique has been implemented on thermally poled silica
      samples, revealing the initial growth of the nonlinear region.

PMID- 18066223
TI  - Reconstruction of the Wigner transform of a rotationally symmetric two
      dimensional beam from the Wigner transform of the beam's one-dimensional sample.
AB  - A coherent rotationally symmetric two-dimensional beam is essentially one
      dimensional in content: It is fully determined by the one-dimensional sample
      along a diagonal of the circularly symmetric field distribution in a transverse
      plane. The linear transform that reconstructs the four-dimensional Wigner
      distribution of the full two-dimensional beam from the two-dimensional Wigner
      distribution of the one-dimensional sample is presented.

PMID- 18066224
TI  - Waveguide atom beam splitter for laser-cooled neutral atoms.
AB  - A laser-cooled neutral-atom beam from a low-velocity intense source is split into
      two beams while it is guided by a magnetic-field potential. We generate our
      multimode beam-splitter potential with two current-carrying wires upon a glass
      substrate combined with an external transverse bias field. The atoms are guided
      around curves and a beam-splitter region within a 10-cm guide length. We achieve
      a maximum integrated flux of 1.5x10(5)atoms/s with a current density of
      5x10(4)amp/cm (2) in the 100-microm -diameter wires. The initial beam can be
      split into two beams with a 50/50 splitting ratio.

PMID- 18066225
TI  - Analysis of radiation pressure exerted on a metallic particle within an
      evanescent field.
AB  - Radiation pressure induced by an evanescent field was experimentally analyzed for
      a single submicrometer-sized gold particle. The force measurement was based on a
      thermodynamic analysis of Brownian motion by use of a three-dimensional position
      sensing technique. The lateral radiation pressure could be ascribed to a
      scattering force, which was oriented in the same direction as the propagation
      vector of the incident laser beam. The potential profile in the longitudinal
      direction indicated that the gold particle was attracted to the high-intensity
      region of the evanescent field by a gradient force.

PMID- 18066226
TI  - Backscattering peak of hexagonal ice columns and plates.
AB  - The backward cross section of hexagonal ice crystals of arbitrary orientation is
      calculated for visible light by means of a ray-tracing code. It is shown that
      backscattering of the tilted crystals is caused by a corner-reflector-like
      effect. A very large peak of backscattering is found for a tilt of 32.5 degrees
      between the principal particle axis and the incidence direction. This peak is
      caused by multiple total internal reflections for part of the rays that are
      incident upon the skewed rectangular faces. Slant lidar measurements for remote
      sensing of cirrus clouds are proposed.

PMID- 18066227
TI  - Bacteriorhodopsin: a natural (nonlinear) photonic bandgap material.
AB  - The angular dependence of the hyper-Rayleigh scattered light intensity from a
      suspension of bacteriorhodopsin has been analyzed. The observation calls for
      combination of the second-order nonlinear hyperpolarizability of the retinal
      chromophore with the linear refractive index of the apo-protein matrix. The
      structuring of the small nonlinear chromophore in the large linear matrix imparts
      properties of a photonic bandgap to bacteriorhodopsin.

PMID- 18066228
TI  - Femtosecond nonlinear polarization evolution based on cascade quadratic
      nonlinearities.
AB  - We experimentally demonstrate that one can exploit nonlinear phase shifts
      produced in type I phase-mismatched second-harmonic generation to produce
      intensity-dependent polarization evolution with 100-fs pulses. An amplitude
      modulator based on nonlinear polarization rotation provides passive amplitude
      modulation depth of up to ~50%. Applications of the amplitude and phase
      modulations to mode locking of femtosecond bulk and fiber lasers are promising
      and are discussed.

PMID- 18066229
TI  - Infrared extension of the super continuum generated by femtosecond terawatt laser
      pulses propagating in the atmosphere.
AB  - We investigated the spectral behavior of a white-light continuum generated in air
      by 2-TW femtosecond laser pulses at 800 nm. The spectrum extends at least from
      300 nm to 4.5 mum. From 1 to 1.6 mum the continuum's intensity increases strongly
      with the laser energy and depends on the initial chirp.

PMID- 18066230
TI  - Simple grating synthesis algorithm: errata.

PMID- 18066231
TI  - Focusing by small-f-number lenses in the presence of aberrations.
AB  - A method of finding the three-dimensional distribution of light in the focal
      region of small- f -number lenses that have arbitrary surface curvatures is
      described. The Fresnel approximation is not used, and the effects of aberration
      are included. A comparison of the numerical results with experimental
      measurements for a commercially obtained plano-convex lens is provided.

PMID- 18066232
TI  - Measurements of thermal effects on four-photon mixing conversion efficiency in an
      optical fiber.
AB  - Thermal effects on the conversion efficiency of four-photon mixing (FPM) power in
      a silica optical fiber are measured. When the temperature of the fiber changes
      from 9 to 350 degrees C, the first Stokes power decreases with a temperature
      coefficient of -0.33%/ degrees C as the temperature increases to 200 degrees C
      and then becomes saturated with a further increase in temperature. This
      temperature characteristic of the first Stokes power reflects the temperature
      characteristics of the nonlinear refractive index of the fiber, which are similar
      to its FPM temperature dependence.

PMID- 18066233
TI  - Supercontinuum generation in tapered fibers.
AB  - Supercontinuum light with a spectrum more than two octaves broad (370-1545 nm at
      the 20-dB level) was generated in a standard telecommunications fiber by
      femtosecond pulses from an unamplified Ti:sapphire laser. The fiber had been
      tapered to a diameter of :2mum over a 90-mm length. The pulse energy was 3.9 nJ
      (average power, 300 mW). This source of high-intensity single-mode white light
      should find widespread applications in frequency metrology and spectroscopy,
      especially since no unconventional fibers are needed.

PMID- 18066234
TI  - Gigahertz-repetition-rate mode-locked fiber laser for continuum generation.
AB  - We report direct generation of <500-fs pulses at a 1-GHz rate from a self
      starting passively mode-locked fiber laser by regeneratively synchronizing the
      pulses with a phase modulator. The pulses are amplified and passed through a
      dispersion-decreasing fiber and a normal-dispersion supercontinuum fiber. The
      resulting continuum is wider than 350 nm.

PMID- 18066235
TI  - Passive harmonic mode-locked soliton fiber laser stabilized by an optically
      pumped saturable Bragg reflector.
AB  - Stabilization of passive harmonic mode locking is achieved for what is believed
      to be the first time in an Er-Yb soliton fiber laser by optical pumping of the
      semiconductor saturable absorber above the bandgap. The results show 35-dB mode
      suppression of undesired harmonics.

PMID- 18066236
TI  - Fringe pattern correlator for three-dimensional object recognition.
AB  - We propose a novel three-dimensional (3-D) object-recognition method based on a
      Fourier-transform profilometry technique and a two-dimensional (2-D) correlation
      technique. Height information on 3-D objects is transformed to phase information
      on 2-D complex amplitude by use of the Fourier-transform profilometry technique.
      3-D objects are recognized using correlation by use of the transformed complex
      amplitude.

PMID- 18066237
TI  - Characterization and application of a channel- planar composite waveguide.
AB  - A new structural waveguide, which is referred to as a channel-planar composite
      optical waveguide (COWG), has been fabricated by sputtering of a titanium dioxide
      (TiO>(2)) film onto a glass substrate with potassium ion-exchanged channel
      waveguides. By use of a mask during deposition, the TiO(2) film was formed into a
      27-nm-thick, 5-mm-wide strip with two 1-mm-long tapered ends perpendicular to the
      channel waveguides. Adiabatic transition of the TE(00) mode and the TE(00)-
      TM(00) mode separation inside such a channel-planar COWG were demonstrated by
      combination of theoretical analysis and measurement of the experimental
      attenuation that arises from scattering loss and evanescent-field dye absorption.
      Changing the superstrate index in the region of the TiO(2) film in the channel
      planar COWG yielded polarimetric interference patterns. This new technique can be
      applied to integrated optical chemical and biological sensors to produce enhanced
      sensitivity.

PMID- 18066238
TI  - Fiber-coupled microsphere laser.
AB  - We demonstrate a 1.5-microm - wavelength fiber laser formed by placement of glass
      microsphere resonators along a fiber taper. The fiber taper serves the dual
      purpose of transporting optical pump power into the spheres and extracting the
      resulting laser emission. A highly doped erbium:ytterbium phosphate glass was
      used to form microsphere resonant cavities with large gain at 1.5microm . Laser
      threshold pump powers of 60muW and fiber-coupled output powers as high as 3 muW
      with single-mode operation were obtained. A bisphere laser system consisting of
      two microspheres attached to a single fiber taper is also demonstrated.

PMID- 18066239
TI  - Ion-exchanged tapered-waveguide laser in neodymium-doped BK7 glass.
AB  - We report what is to our knowledge the first operation of a planar dielectric
      tapered-waveguide laser. The waveguide laser is fabricated by potassium-ion
      exchange in Nd(3+) -doped BK7 glass and consists of a single-mode channel
      waveguide of a few micrometers' width followed by a linear taper up to a broad
      region with a width of ~180microm . A slope efficiency of 42% is found both in
      the tapers and in standard channel waveguides fabricated upon the same substrate,
      indicating that the tapers and the channels have similar internal losses; hence
      the low-loss nature of the tapered beam expansion. The output from either end of
      the tapered structure is found to be nearly diffraction limited.

PMID- 18066240
TI  - Phase locking in a multicore fiber laser by means of a Talbot resonator.
AB  - We report phase locking of a diode-pumped multicore fiber laser with a circular
      array of 18 Nd-doped emitters (microcores) acting as an active medium. Phase
      locking was achieved in a Talbot resonator configuration. We present calculations
      of the effective reflection coefficients that are due to self-imaging. Far-field
      distributions and near-field pattern of several supermodes are calculated and
      compared with experimental results.

PMID- 18066241
TI  - Properties of the pulse train generated by repetition-rate-doubling rational
      harmonic actively mode-locked Er-doped fiber lasers.
AB  - We demonstrate for the first time to our knowledge, experimentally and
      theoretically, that the pulse-to-pulse amplitude fluctuations that occur in pulse
      trains generated by actively mode-locked Er-doped fiber lasers in a repetition
      rate-doubling rational-harmonic mode-locking regime are completely eliminated
      when the modulation frequency is properly tuned. Irregularity of the pulse
      position in the train was found to be the only drawback of this regime. One could
      reduce the irregularity to a value acceptable for applications by increasing the
      bandwidth of the optical filter installed in the laser cavity.

PMID- 18066242
TI  - High-power diode-pumped Q-switched and mode-locked Nd:YVO(4) laser with a
      Cr(4+):YAG saturable absorber.
AB  - We demonstrate a high-power passively Q -switched and mode-locked Nd:YVO(4) laser
      with a Cr(4+):YAG saturable absorber. 2.7 W of average power with an 18-kHz Q 
      switched repetition rate was generated at a 12.5-W pump power. The peak power of
      a single pulse near the maximum of the Q -switched envelope was greater than 100
      kW.

PMID- 18066243
TI  - Actively mode-locked visible upconversion fiber laser.
AB  - Active mode locking of a Pr(3+)/Yb (3+) -doped upconversion fluoride fiber laser
      with an all-fiber ZnO acousto-optic phase modulator is demonstrated for the first
      time to the authors' knowledge. Optical pulses of ~550-ps duration with a
      repetition rate of 239 MHz at a wavelength of 635 nm have been generated.

PMID- 18066244
TI  - Imaging and velocimetry of the human retinal circulation with color Doppler
      optical coherence tomography.
AB  - Noninvasive monitoring of blood flow in retinal microcirculation may elucidate
      the progression and treatment of ocular disorders, including diabetic
      retinopathy, age-related macular degeneration, and glaucoma. Color Doppler
      optical coherence tomography (CDOCT) is a technique that allows simultaneous
      micrometer-scale resolution cross-sectional imaging of tissue microstructure and
      blood flow in living tissues. CDOCT is demonstrated for the first time in living
      human subjects for bidirectional blood-flow mapping of retinal vasculature.

PMID- 18066245
TI  - Turbidity-free fluorescence spectroscopy of biological tissue.
AB  - We present a method based on photon migration of extracting intrinsic
      fluorescence spectra from turbid media, using concomitantly measured fluorescence
      and reflectance. Intrinsic fluorescence is defined as fluorescence that is due
      only to fluorophores, without interference from the absorbers and scatterers that
      are present. Application to fluorescence spectra taken with tissue phantoms and
      human mucosal tissues demonstrates excellent agreement in both spectral line
      shape and intensity between the extracted and the directly measured intrinsic
      fluorescence spectra.

PMID- 18066246
TI  - Bloch domain walls in type II optical parametric oscillators.
AB  - Evidence of Bloch domain walls in nonlinear optical systems is given. These walls
      are found in the transverse fields of optical parametric oscillators when the
      polarization degree of freedom, the cavity birefringence, and (or) dichroism are
      taken into account. These domain walls arise spontaneously and exhibit defects
      where Bloch walls of different chirality join together. Two dynamic regimes are
      found:In the first one the vector field approaches a final homogeneous state, and
      in the other the walls are continually generated and annihilated. This dynamic
      behavior is caused by the fact that walls of opposite chirality move
      spontaneously with opposite velocity.

PMID- 18066247
TI  - Development of a high-power deep-ultraviolet continuous-wave coherent light
      source for laser cooling of silicon atoms.
AB  - We developed a deep-UV single-mode coherent light source through two-stage highly
      efficient frequency conversions by use of external cavities. In the first stage,
      second-harmonic power of 500 mW was obtained by frequency doubling of a 746-nm
      Ti:sapphire laser with a conversion efficiency of 40%. In the second stage, 50-mW
      power at ~252nm was obtained by doubly resonant sum-frequency mixing of 373-nm
      light from the first-stage conversion and 780-nm light from a diode laser. The
      output performance of this deep-UV light source is sufficient for laser cooling
      of neutral silicon atoms.

PMID- 18066248
TI  - Compact 21-W 2-mum intracavity optical parametric oscillator.
AB  - We report on an intracavity optical parametric oscillator (OPO) placed within a
      compact diode-pumped Nd:YALO laser cavity. This OPO utilizes a pair of KTP
      crystals, which are diffusion bonded together in a walk-off-compensated
      configuration. We have generated up to 21.4 W of 2-mum radiation, operating in a
      few-kilohertz range.

PMID- 18066249
TI  - Propagation of electromagnetic dipole waves through dielectric interfaces.
AB  - The problem of divergent electromagnetic dipole waves propagating through
      parallel dielectric interfaces is solved. The solution is obtained in an analytic
      form that can be readily evaluated numerically. The result is obtained as a
      solution to a boundary-value problem. Applications of the solution are described.

PMID- 18066250
TI  - Double-edge molecular measurement of lidar wind profiles at 355 nm.
AB  - We built a direct-detection Doppler lidar based on the double-edge molecular
      technique and made the what we believe to be the first molecular-based wind
      measurements using the eye-safe 355-nm wavelength. Three etalon bandpasses are
      obtained with step etalons on a single pair of etalon plates. We eliminate long
      term frequency drift of the laser and the capacitively stabilized etalon by
      locking the etalon to the laser frequency. We use a low-angle design to avoid
      polarization effects. Wind measurements of 1-2-m /s accuracy are obtained to 10
      km altitude with 5 mJ of laser energy, a 750-s integration, and a 25-cm
      telescope. Good agreement is obtained between lidar and rawinsonde measurements.

PMID- 18066251
TI  - Two-line atomic fluorescence as a temperature probe for highly sooting flames.
AB  - We investigate the applicability of two-line atomic fluorescence (TLAF) from
      seeded indium atoms for temperature measurements in highly sooting flames. The
      results show that TLAF holds promise for two-dimensional temperature measurements
      in sooting and fuel-rich flames under conditions in which other thermometry
      techniques fail, a result that is attributed to the superior characteristics of
      the indium atomization process. Furthermore, no native species was found to
      interfere spectrally with the detected TLAF wavelengths. Advantages of and
      problems with the technique are discussed.

PMID- 18066252
TI  - Controlled shaping of ultrafast electric field transients in the mid-infrared
      spectral range.
AB  - We experimentally demonstrate amplitude and phase shaping of femtosecond mid
      infrared pulses in a range centered about 14 mum . Single pulses with a tailored
      optical phase and phase-locked double pulses are generated by phase-matched
      difference-frequency mixing in a GaSe crystal of near-infrared pulses shaped with
      a liquid-crystal modulator. The electric field transients are directly measured
      by free-space electro-optic sampling, yielding pulse durations of 200-300 fs. Our
      data are in good agreement with a model that describes phase-matched optical
      rectification.

PMID- 18066253
TI  - Timing-jitter reduction of a mode-locked Cr:LiSAF laser by simultaneous control
      of cavity length and pump power.
AB  - The pulse-repetition frequency of a mode-locked Cr:LiSAF laser has been
      stabilized to an electrical reference signal by simultaneous control of the laser
      cavity length and the pump power. The phase difference between the laser pulse
      and an electrical reference signal is detected by use of a digital phase detector
      and fed back to a piezoelectric transducer and to a laser diode injection
      current. A rms timing jitter of 7.5 fs relative to the reference was obtained for
      the 25-mHz-10-kHz bandwidth.

PMID- 18066254
TI  - Amplitude and phase measurement of mid-infrared femtosecond pulses by using cross
      correlation frequency-resolved optical gating.
AB  - We describe a cross-correlation-based frequency-resolved optical gating (XFROG)
      technique for simultaneously measuring the amplitude and phase of two ultrashort
      pulses that have different wavelengths but are derived from a common mode-locked
      oscillator. A measurement is presented in which 4.0-mum mid-IR pulses from a
      synchronously pumped femtosecond optical parametric oscillator (OPO) are
      characterized by mixing with the 770-nm OPO pump pulses. Details of the pulse
      retrieval algorithm are included, together with examples of pulse data retrieved
      from the experimentally measured XFROG trace.

PMID- 18066255
TI  - 40-GHz pulse-train generation at 1.5 mum with a chirped fiber grating as a
      frequency multiplier.
AB  - Pulse-train multiplication based on the temporal Talbot effect in a linearly
      chirped fiber Bragg grating has been experimentally demonstrated. A 40-GHz
      repetition-rate, nearly transform-limited 10-ps duration optical pulse train at
      1.533 mum has been obtained from a 2.5-GHz mode-locked Er- Yb:glass laser by use
      of a 100-cm-long linearly chirped apodized fiber grating.

PMID- 18066256
TI  - Alternative formulation for invariant optical fields: Mathieu beams.
AB  - Based on the separability of the Helmholtz equation into elliptical cylindrical
      coordinates, we present another class of invariant optical fields that may have a
      highly localized distribution along one of the transverse directions and a
      sharply peaked quasi-periodic structure along the other. These fields are
      described by the radial and angular Mathieu functions. We identify the
      corresponding function in the McCutchen sphere that produces this kind of beam
      and propose an experimental setup for the realization of an invariant optical
      field.

PMID- 18066257
TI  - Stability and optimization of dispersion-managed soliton control.
AB  - Dispersion-managed solitons with in-line all-optical regeneration are shown to be
      subject to amplitude and timing-jitter instabilities. We identify and discuss the
      different natures of these instabilities by means of a linear stability analysis,
      which is in good agreement with the full numerical solutions of the governing
      equations. Stable pulse propagation can be achieved through appropriate choices
      of dispersion map and pulse energy.

PMID- 18066258
TI  - Excitation of cladding modes in photonic crystal fibers by flexural acoustic
      waves.
AB  - We report the excitation by flexural acoustic waves of an individual cladding
      mode in a single-mode photonic crystal fiber. The propagation constant and the
      field distributions of the mode have been investigated by use of this technique.
      The results give the basis for developing a family of acousto-optic devices based
      on photonic crystal fibers.

PMID- 18066259
TI  - Use of a dielectric stack as a one-dimensional photonic crystal for wavelength
      demultiplexing by beam shifting.
AB  - We demonstrate the use of a 30-period dielectric stack structure as a highly
      dispersive device to spatially separate two beams with a 4-nm wavelength
      difference by more than their beam width. Unlike previous devices, our structure
      is simple to fabricate and relatively compact. We discuss possible applications
      of our device within wavelength-division multiplexing systems.

PMID- 18066260
TI  - Interference microscopy for three-dimensional imaging with wavelength-to-depth
      encoding.
AB  - A novel interference microscope for three-dimensional (3D) imaging based on a
      wavelength-to-depth encoding technique is presented. Wavelength-to-depth encoding
      is realized by use of a diffractive lens and wavelength tuning. A high depth
      resolution of 0.71 mum is obtained with 0.90-N.A. objective lenses. Experimental
      measurements of a four-level grating are presented, and the results are found to
      be comparable with those obtained with a Dektak profilometer and a similar
      interference microscope that uses mechanical depth scanning. The system is
      promising for fast, noncontact, high-resolution 3D imaging.

PMID- 18066261
TI  - Method for measuring the diffusion coefficient of homogeneous and layered media.
AB  - A method for measuring the diffusion coefficient of homogeneous and layered
      media, based on multidistance measurements of time-resolved reflectance, is
      proposed. The diffusion coefficient is retrieved from the logarithm between two
      measurements of reflectance at two different distances. The proposed procedure is
      simpler than others usually employed and also provides a reliable criterion for
      retrieval of information on the layered structure of a diffusive medium.

PMID- 18066262
TI  - Enhanced photomultiplier sensitivity in spectroscopy systems.
AB  - A fiber-ribbon-based coupling method is presented as a practical way to enhance
      light sensitivity in spectroscopic and similar systems employing a multialkali
      photomultiplier tube as a detector. The sensitivity enhancement is achieved by an
      increase in absorption in the photocathode through multiple total internal
      reflection in the photomultiplier entrance window. Improvements by factors of
      approximately 2 (blue-green) to more than 10 (near infrared) have been measured.
      Implications for spectroscopic applications are discussed.

PMID- 18066263
TI  - Measurement of the internal lasing intensity distribution of a dye-doped pendant
      drop.
AB  - The lasing intensity distribution made inside a circular resonator formed by a
      dye-doped pendant drop was measured by addition of polymer particles to the dye
      solution to enhance the elastic-scattered light of the lasing inside the pendant
      drop. A theory that connects wave and ray pictures in dealing with the cavity
      resonance is used to calculate the internal intensity distribution. The
      experimental and theoretical results are in good agreement for sufficiently large
      densities of scattering particles, such that the cavity mode efficiency phi is
      approximately 1 for all resonant modes.

PMID- 18066264
TI  - Polarized optical coherence imaging in turbid media by use of a Zeeman laser.
AB  - A method that uses a Zeeman laser in conjunction with a Glan-Thompson analyzer to
      image an object in a turbid medium is proposed. A heterodyne signal is generated
      only when the scattering photons are partially polarized, and the spatial
      coherence is not seriously degraded after the signal propagates in the turbid
      medium. A system combining polarization discrimination with optical coherence
      detection to image the object in a scattering medium is successfully
      demonstrated. The medium is a solution of polystyrene microspheres measuring
      1.072 mum in diameter suspended in distilled water contained in a 10-mm-thick
      quartz cuvette. The advantages of this optical system, including better
      selectivity of the weak partially polarized scattering photons and better imaging
      ability in higher-scattering media, are discussed.

PMID- 18066265
TI  - Imaging needle for optical coherence tomography.
AB  - We describe a miniature optical coherence tomography (OCT) imaging needle that
      can be inserted into solid tissues and organs to permit interstitial imaging of
      their internal microstructures with micrometer scale resolution and minimal
      trauma. A novel rotational coupler with a glass capillary tube is also presented
      that couples light from a rotating single-mode fiber to a stationary one. A
      prototype needle with a 27-gauge (approximately 410-microm) outer diameter has
      been developed and is demonstrated for in vivo imaging. The OCT needle can be
      integrated with standard excisional biopsy devices and used for OCT-guided
      biopsy.

PMID- 18066266
TI  - Doppler-angle measurement in highly scattering media.
AB  - We describe a dual-channel optical low-coherence reflectometer for accurate
      measurement of Doppler angles in highly scattering media. Accurate fluid-flow
      velocity estimation requires measurement of the Doppler shift and angle.
      Estimated values of the Doppler angle and average fluid-flow velocity from
      experimental data are in good agreement with preset values.

PMID- 18066267
TI  - Interferometric phase-dispersion microscopy.
AB  - We describe a new scanning microscopy technique, phase-dispersion microscopy
      (PDM). The technique is based on measuring the phase difference between the
      fundamental and the second-harmonic light in a novel interferometer. PDM is
      highly sensitive to subtle refractive-index differences that are due to
      dispersion (differential optical path sensitivity, 5 nm). We apply PDM to measure
      minute amounts of DNA in solution and to study biological tissue sections. We
      demonstrate that PDM performs better than conventional phase-contrast microscopy
      in imaging dispersive and weakly scattering samples.

PMID- 18066268
TI  - Subwavelength depth resolution in near-field microscopy.
AB  - A generalized Radon transform is presented that relates, for the case of an
      evanescent wave that is incident upon a weakly scattering medium, the homogeneous
      components of the scattered field to the three-dimensional Fourier transform of
      the dielectric susceptibility. This relationship is used within the context of
      total internal reflection microscopy to reconstruct the depth structure of the
      dielectric susceptibility from simulated scattered field data.

PMID- 18066269
TI  - Extreme-ultraviolet harmonic generation near 13 nm with a two-color elliptically
      polarized laser field.
AB  - Theoretical results for high-harmonic generation by a two-color elliptically
      polarized laser field are presented. Special emphasis is placed on coherent
      radiation near 13 nm in connection with the development of extreme-ultraviolet
      lithography. Linearly polarized radiation at this wavelength can be obtained with
      a linearly polarized bichromatic laser field, whereas circularly polarized
      radiation can be generated with a bichromatic circularly polarized field with
      counterrotating coplanar components. In both cases the harmonic emission
      efficiencies at the saturation intensity are more than 1 order of magnitude
      larger than for harmonic generation with a monochromatic linearly polarized
      field.

PMID- 18066270
TI  - Multipoint temperature and oxygen-concentration measurements using rotational
      coherent anti-Stokes Raman spectroscopy.
AB  - A novel technique for coherent anti-Stokes Raman spectroscopy (CARS) measurements
      in multiple points is presented. With a system of cylindrical lenses, each laser
      beam is split into several focused beams, yielding separate planar boxcars
      configurations. Spectrally resolved CARS signals are detected at different
      heights on the CCD chip. With dual-broadband rotational CARS the setup is
      demonstrated for quantitative measurements of temperature- and oxygen
      concentration profiles. The technique was demonstrated for three points only, but
      it can be extended to more points by use of special optics; this choice must be
      based on a sufficient signal-to-noise ratio in all points for the actual
      measurement condition.

PMID- 18066271
TI  - Stable oscillating nonlinear beams in square-wave-biased photorefractives.
AB  - We demonstrate experimentally that, in a paraelectric, nonstationary boundary
      conditions can dynamically halt the intrinsic instability of quasi-steady-state
      photorefractive self-trapping, driving beam evolution into a stable oscillating
      two-soliton-state configuration.

PMID- 18066272
TI  - Guided-wave multiwavelength polarization-insensitive processing module for a
      parallel multicomparand perfect-match algorithm.
AB  - We present a design for a planar guided-wave polarization-insensitive (intensity
      based) optoelectronics module that provides a parallel perfect-match search for
      database and text processing. The module is based on a content-addressable memory
      model for parallel information retrieval. We propose the use of planar guided
      wave optics with multiwavelength processing to achieve a substantially high
      degree of performance and parallelism. Based on initial performance analysis, the
      proposed module is capable of achieving an aggregate processing speed of 10(12)
      bits/s.

PMID- 18066273
TI  - Synthetic aperture radar image correlation by use of preprocessing for
      enhancement of scattering centers.
AB  - We demonstrate that a significant improvement can be obtained in the recognition
      of complicated synthetic aperture radar images taken from the Moving and
      Stationary Target Acquisitions and Recognition database. These images typically
      have a low number of scattering centers and high noise. We first preprocess the
      images and the templates formed from them so that their scattering centers are
      enhanced. Our technique can produce high-quality performance in several
      correlation criteria. For realistic automatic target recognition systems, our
      approach should make it easy to implement optical recognition systems with
      binarized data for many different types of correlation filter and should have a
      great effect on feeding data-compressed (binarized) information into either
      digital or optical processors.

PMID- 18066274
TI  - Nontwist quarter-wave liquid-crystal cell for a high-contrast reflective display.
AB  - We propose an optical configuration of a nontwist quarter-wave liquid-crystal
      cell for a high-contrast reflective display that can be applied to most nontwist
      display modes. By fabricating a homogeneous cell with the proposed configuration,
      we have demonstrated a high contrast ratio of 50:1 without using a wideband
      retardation film.

PMID- 18066275
TI  - Single-mode transmission in two-dimensional macroporous silicon photonic crystal
      waveguides.
AB  - We report the infrared operation of a two-dimensional photonic crystal waveguide
      fabricated in silicon. Measurements of the transmission spectrum reveal a large
      transmission bandwidth within the 3.1-5.5-microm bulk-crystal photonic bandgap
      and a rich resonance structure. The calculated transmission spectrum for this
      structure is in good agreement with the measured spectrum and predicts a 10%
      single-mode bandwidth for the waveguide.

PMID- 18066276
TI  - Intensity-induced mode shift in a femtosecond laser by a change in the nonlinear
      index of refraction.
AB  - The modes of the comb spectrum of a Kerr-lens mode-locked laser are frequency
      shifted versus the corresponding cw modes of the cavity by an intensity-induced
      change in the index of refraction in the Kerr medium. We demonstrate this effect
      and discuss novel schemes for fast frequency control of the comb spectrum.

PMID- 18066277
TI  - Quadrupole radiation from terahertz dipole antennas.
AB  - We report what is to our knowledge the first detailed investigation of the
      polarization state of radiation from lens-coupled terahertz dipole antennas. The
      radiation exhibits a weak but measurable component that is polarized orthogonally
      to the orientation of the emitter dipole. The angular radiation pattern of this
      cross-polarized emission reveals that it is quadrupolar, rather than dipolar, in
      nature. One can understand this result by taking into account the photocurrent
      flowing in the strip lines that feed the dipole antenna. A Fresnel-Kirchhoff
      scalar diffraction calculation is used for calculating the frequency-dependent
      angular distribution of the radiation pattern, providing satisfactory agreement
      with the measurements.

PMID- 18066278
TI  - Homomorphic cameo filter for pattern recognition that is invariant with changes
      in illumination.
AB  - We introduce a new matched filter method that yields correlation peaks that are
      invariant with changes in the illumination of any targets. A scene containing
      objects at unknown locations is first subjected to a logarithmic transformation
      that changes the multiplicative constant to an additive background, which is then
      discriminated against by means of a composite filter containing a cameo of the
      true target and a term with which to discriminate against other false targets.
      Experimental results are shown.

PMID- 18066279
TI  - Combinational tasks performed by second-harmonic-generated holograms.
AB  - Second-harmonic-generated holograms directly provide the outputs of logical gates
      AND and NAND operating on optical bits encoded as amplitude modulations in the
      object and reference wave fronts. By use of a Nd:YAG laser and a beta-barium
      borate crystal, we realized a real-time half-adder of two one-digit binary
      numbers. The feasibility of highly parallel operation is also discussed.

PMID- 18066280
TI  - Multichannel Mueller matrix ellipsometer for real-time spectroscopy of
      anisotropic surfaces and films.
AB  - A multichannel ellipsometer in the dual-rotating-compensator configuration has
      been developed for potential applications in real-time Mueller matrix
      spectroscopy of anisotropic surfaces and films. This instrument provides spectra
      (1.7-5.3 eV) in all 16 elements of the unnormalized Mueller matrix M of a film
      substrate system with a minimum overall data acquisition time of t(a) = 0.25 s.
      We have applied this instrument first for high-precision determination of spectra
      in M with t(a) = 2.5 s for a microscopically sculptured film.

PMID- 18066281
TI  - Multimode semiconductor laser with selective optical feedback.
AB  - We study a multimode semiconductor laser subject to moderate selective optical
      feedback. The steady state of the laser is destabilized by a Hopf bifurcation and
      exhibits a period-doubling route to chaos. We also show the existence of a
      heteroclinic connection between a saddle node and an unstable focus that can be
      associated with experimentally observed multimode low-frequency fluctuations.
      This heteroclinic connection coexists with a chaotic attractor resulting from the
      period-doubling process.

PMID- 18066282
TI  - Spatial mode control of a diode-pumped Nd:YAG laser by use of an intracavity
      holographic phase plate.
AB  - We present a new method of realizing phase plates by phase-volume holography on a
      photopolymer film. We implement such a component in a diode-pumped Nd:YAG
      oscillator to control the output spatial beam profile. Flattop super-Gaussian and
      square-shaped beams are obtained.

PMID- 18066283
TI  - Experimental observation of the slowdown of optical beams by a volume-index
      grating in a photorefractive LiNbO3 crystal.
AB  - We investigate the group velocity of light in a one-dimensional volume-index
      grating inside a photorefractive LiNbO(3) crystal. The slowdown of the group
      electromagnetic propagation is observed experimentally by tuning of the wave
      number of the optical beam close to the outside edge of the forbidden bandgap. We
      obtain a large group index of up to 7.5 in a 3.5-cm crystal sample. The group
      index is compared with the result of a theoretical derivation. The results are
      presented and discussed.

PMID- 18066284
TI  - Intensity-dependent parametric amplification for traveling-wave signal
      processing.
AB  - We propose and demonstrate a nonlinear parametric amplification system that
      relies on sequential use of a nonlinear phase shift (Kerr-like effect) and on
      phase-sensitive parametric amplification. We demonstrate amplification that is
      50% better than with a bare phase-sensitive amplifier as well as two additional
      effects: inversion of weak optical modulation and suppression of classical noise.

PMID- 18066285
TI  - Alleviation of photoinduced damage in GdxY1-xCa4O(BO3)3 at elevated crystal
      temperature for noncritically phase-matched 355-nm generation.
AB  - We developed a Gd(x)Y(1-x)Ca(4)O(BO(3))(3) (GdYCOB) crystal for control of
      optical birefringence. GdYCOB crystals were successfully used to generate
      noncritical phase-matched (NCPM) second and third harmonics of 1064-nm lights.
      However, we observed degradation of third-harmonic-generation (THG) output power
      and distortion of the beam pattern as a result of photoinduced damage and thermal
      dephasing. The photoinduced damage was classified into two types. One was gray
      track and the other was photorefractive damage. It seems that these types of
      damage were similar to the types of damage that occurred with KTiOPO(4) and
      LiNbO(3) crystals. We tried to circumvent this problem by crystal heating.
      Photoinduced damage of GdYCOB was overcome by elevation of the crystal
      temperature, and NCPM THG (355-nm) output power from heated GdYCOB increased to 9
      mW (62.5 kHz).

PMID- 18066286
TI  - 120-W continuous-wave diode-pumped Tm:YAG laser.
AB  - We present a 120-W cw diode-pumped Tm:YAG laser. The Tm:YAG rod is side pumped by
      three diode arrays whose radiation is coupled through compound parabolic
      concentrators. The maximum optical-to-optical conversion efficiency of the 2.02
      mum laser output is 25.2%, with a slope efficiency of 31.2%.

PMID- 18066287
TI  - Light-induced specular-reflectivity suppression at a gallium/silica interface.
AB  - The reflectivity of a gallium/silica interface formed on an optical flat or at
      the tip of a cleaved optical fiber can be reduced in a reversible fashion when
      the interface is excited by a few milliwatts of laser power. This phenomenon
      occurs at temperatures just below gallium's melting point. We believe that the
      effect can be attributed to light-induced structuring at the interface.

PMID- 18066288
TI  - Interferometric method of suppressing the pattern effect in a semiconductor
      optical amplifier.
AB  - A new idea of using change in index of refraction to suppress gain variation in a
      saturated semiconductor optical amplifier (SOA) is presented. This kind of gain
      compensation has the advantage of high speed because it involves two phenomena
      that always accompany each other. This compensation can be achieved with a
      nonsymmetrical Mach-Zehnder interferometer structure. Calculated results show
      that with this structure the input and output power of the SOA can be extended to
      nearly 10 dB from the former small-signal limit when less than 1-dB gain
      variation is permitted. Numerical simulations with an advanced dynamic model of
      the SOA agree with the calculated results.

PMID- 18066289
TI  - Coupling semiconductor nanocrystals to a fused-silica microsphere: a quantum-dot
      microcavity with extremely high Q factors.
AB  - We demonstrate a quantum-dot microcavity by coupling core-shell semiconductor
      nanocrystals to a fused-silica microsphere. We show that the composite
      microcavity can feature Q factors of the order of 10(8), providing a model system
      for investigating cavity QED and microlasers at the level of single quantum dots.

PMID- 18066290
TI  - Improved short-term stability of optical frequency standards: approaching 1 Hz in
      1 s with the Ca standard at 657 nm.
AB  - For a neutral (40)Ca-based optical frequency standard we report a fractional
      frequency instability of 4 x 10(-15) in 1 s, which represents a fivefold
      improvement over existing atomic frequency standards. Using the technique of
      optical Borde-Ramsey spectroscopy with a sample of 10(7) trapped atoms, we have
      resolved linewidths as narrow as 200 Hz (FWHM). With colder atoms this system
      could potentially achieve an instability as low as 2 x 10(-16) in 1 s. Such low
      instabilities are important for frequency standards and precision tests of
      fundamental physics.

PMID- 18066291
TI  - Real-time detection of 13CH4 in ambient air by use of mid-infrared cavity leak
      out spectroscopy.
AB  - We report on spectroscopic real-time detection of (13)CH(4) in ambient air. Our
      measurements were carried out by means of cavity leak-out absorption spectroscopy
      employing a tunable cw laser in the mid-infrared spectral region near lambda = 3
      microm. A CO laser in combination with tunable microwave sideband generation was
      used as the light source. Using a 50-cm-long ringdown cell with R = 99.98%
      mirrors, we achieved a detection limit of 290 parts in 10(12) (ppt) (13)CH(4) in
      ambient air (integration time, 100 s). The corresponding noise-equivalent
      absorption coefficient was 5 x 10(-9)/cm.

PMID- 18066292
TI  - Optical phonon dynamics of GaAs studied with time-resolved terahertz
      spectroscopy.
AB  - We investigate the reflection near the reststrahlen band of the optical phonon in
      bulk GaAs in the time domain, using time-resolved terahertz spectroscopy. We find
      that the dynamics of the reflection measured for GaAs differs strongly from the
      reflection dynamics that would be expected for a TO phonon with a frequency
      independent dephasing time.

PMID- 18066294
TI  - Ultraviolet-induced absorption losses in hydrogen-loaded optical fibers and in
      presensitized optical fibers.
AB  - Reduced hydroxyl formation in presensitized fibers exposed to cw 244-nm light
      after hydrogen outdiffusion is reported. The OH band in the presensitized fiber
      shifts toward 1390 nm. In the fully hydrogen-loaded fiber the OH band is centered
      at 1397 nm and does not shift with fluence.

PMID- 18066295
TI  - Stable single- and dual-wavelength fiber laser mode locked and spectrum shaped by
      a Fabry-Perot saturable absorber.
AB  - We show that the spectral response of a Fabry-Perot semiconductor saturable
      absorber depends on laser beam focusing. We used this effect to achieve stable
      passive mode-locked operation in a simple and environmentally stable fiber laser
      by introducing spectral filtering and forcing near-resonant operation. By
      reducing the free spectral range and increasing the nonlinear response of the
      Fabry-Perot saturable absorber, we obtained dual-wavelength mode-locked
      operation.

PMID- 18066296
TI  - Accumulated programming of a complex spectral grating.
AB  - A complex spectral grating is accumulated by repeated application of a pair of
      low-power optical programming pulses to a short-term persistent inhomogeneously
      broadened transition in Tm:YAG at 4.5 K and then probed to investigate the
      buildup dynamics. The necessary frequency stability is obtained by locking a cw
      Ti:sapphire laser to a regenerating transient spectral hole in the same
      transition. Grating accumulation is demonstrated for both a periodic spectral
      grating, representing a true-time delay, and a complex spectral grating,
      permitting correlation-based pattern recognition. This work is a step toward
      demonstrating an optical coherent transient continuously programmed continuous
      processor.

PMID- 18066297
TI  - Compensation of lens aberrations in digital holography.
AB  - The possibility of compensating for the aberrations of an imaging lens in digital
      holography is outlined theoretically. The principle is demonstrated with a Mach
      Zehnder arrangement and transilluminated objects. Diffraction-limited resolution
      can be obtained with a plano-convex lens. Amplitude and phase objects were
      imaged.

PMID- 18066298
TI  - Single femtosecond exposure recording of an image hologram by spectral hole
      burning in an unstable tautomer of a phthalocyanine derivative.
AB  - We demonstrate, for what we believe is the first time, recording of a femtosecond
      image hologram by illumination with a single pair of high-intensity femtosecond
      pulses in a broad inhomogeneous bandwidth spectral hole-burning material
      consisting of a polymer film doped with anthraceno-phthalocyanine dye molecules.
      High efficiency of spectral hole burning is achieved by preillumination of the
      sample at a low temperature to convert the dye molecules into an unstable
      tautomer form.

PMID- 18066299
TI  - Planar integrated wavelength-drop device based on pedestal antiresonant
      reflecting waveguides and high-Q silica microspheres.
AB  - Whispering-gallery modes in silica microspheres can be accessed very efficiently
      with the recently introduced stripline pedestal antiresonant reflecting optical
      waveguide (SPARROW) structure. This integrated-optics coupling technique creates
      novel application opportunities for the high-Q spherical cavities. We report the
      demonstration of a narrow-band wavelength-drop configuration utilizing SPARROW
      waveguides and a silica microsphere.

PMID- 18066300
TI  - High-energy pulse-burst laser system for megahertz-rate flow visualization.
AB  - A high-pulse-energy megahertz-repetition-rate Nd:YAG-based pulse-burst laser
      system has been developed. The laser can produce a burst of more than 30 pulses,
      with an average energy per pulse of 70 mJ, at up to 1-MHz repetition rate. The
      burst repetition rate is 9 Hz. Coupled with a megahertz-framing-rate CCD camera,
      the frequency-doubled pulse-burst laser system has been successfully used in the
      visualization of shock evolution in a supersonic flow.

PMID- 18066301
TI  - Suppression of intensity noise in a diode-pumped Tm-Ho:YAG laser.
AB  - We investigate the intensity noise induced by pump-power fluctuations in a diode
      pumped single-frequency codoped Tm-Ho:YAG laser and we measure, in the frequency
      domain, the corresponding transfer function. Good agreement between the measured
      transfer functions and the theoretical prediction is found. A relative intensity
      noise level of ~- 110 dB/Hz from ~1 kHz to the relaxation-oscillation frequency,
      with complete suppression of the relaxation-oscillation peak, is achieved by use
      of a suitable optoelectronic feedback circuit.

PMID- 18066302
TI  - Real-time detection technique for Doppler optical coherence tomography.
AB  - We propose and demonstrate a novel detection technique, based on a modified
      electronic phase-locked loop, for Doppler optical coherence tomography. The
      technique permits real-time simultaneous reflectivity and continuous,
      bidirectional velocity mapping in turbid media over a wide velocity range with
      minimal sensitivity penalty compared with conventional optical coherence
      tomography, which is a major advance over current postprocessing and discrete
      parallel detection techniques.

PMID- 18066303
TI  - Time-resolved DNA-microarray reading by an intensified CCD for ultimate
      sensitivity.
AB  - We describe a novel technique for DNA-microarray reading based on time-resolved
      fluorescence measurements. We used an intensified CCD camera with picosecond
      resolution to acquire a set of time-delayed fluorescence images from a mutation
      DNA microarray marked with cyanine 3. We measured the fluorescence lifetimes of
      the marker and the background separately, and we used this information to
      calculate the amplitude map of the marker, starting from the time-delayed images.
      This procedure allowed us to identify hybridized spots that are not visible in
      fluorescence images acquired with continuous-wave detection.

PMID- 18066304
TI  - Ac-Stark shifts in the nonlinear Faraday effect.
AB  - The frequency of the dark resonance in coherent population trapping experiments
      has been measured as a function of the degree of ellipticity and the intensity of
      the probe light. The results have been used to find the quantum limit of
      sensitivity of an optical magnetometer based on the nonlinear Faraday effect.

PMID- 18066305
TI  - Effect of resonator length on a doubly resonant optical parametric oscillator
      pumped by a multilongitudinal-mode beam.
AB  - The resonator length of an optical parametric oscillator (OPO) is normally made a
      short as possible to minimize the signal-buildup time and maximize the output
      energy. We have found that, when a doubly resonant OPO is pumped by a
      multilongitudinal-mode beam, its output energy has a significant maximum when its
      optical length matches that of the pump source, even if this length is much
      greater than the shortest possible for the OPO. We have observed this effect in a
      ZnGeP>(2)-based OPO and reproduced it in numerical simulations.

PMID- 18066306
TI  - Fabrication and evaluation of a freestanding pyroelectric detector made from
      single-crystal LiNbO(3) film.
AB  - We have packaged a rectangular 3 mm x 4 mm, 10-mum-thick Z-cut lithium niobate
      (LiNbO(3)) film produced by crystal ion slicing (CIS) and evaluated its
      performance as a pyroelectric optical detector. We justify the difficulty of
      preparing the film by showing that the freestanding detector has much greater
      sensitivity than the same detector bonded to a substrate. We compare the
      sensitivity of three CIS-film detectors with that of a detector based on a 230
      mum-thick LiNbO(3) plate and describe the detectors' spatial uniformity and noise
      equivalent power.

PMID- 18066307
TI  - Validity of the Debye approximation.
AB  - The validity of the Debye approximation is reexamined. It is shown that for
      paraxial systems with strong aberrations the Debye approximation may not be
      valid, even for systems with a large Fresnel number. The particular case of
      spherical aberration is considered. Extension to high-aperture systems is
      discussed.

PMID- 18066308
TI  - Integrity of semiconductor laser chaotic communications to naive eavesdroppers.
AB  - The integrity of a chaotic encoding technique based on an external-cavity
      semiconductor laser transmitter-receiver system is experimentally examined. A
      semiconductor laser placed in the transmission path of the system is used to
      represent an eavesdropper intercepting a chaotic communication. The eavesdropper
      is able to obtain a copy of the transmission but is unable to decode the message.
      A chaotic communication system based on external-cavity semiconductor lasers is
      seen therefore to be secure against this form of interception.

PMID- 18066309
TI  - Mode density inside an omnidirectional mirror is heavily directional but not
      small.
AB  - We show that ominidirectional reflection is not a sufficient signature of a
      photonic bandgap. Although dramatic angular redistribution takes place, the mode
      density of the electromagnetic field is hardly altered within the
      ominidirectional reflection range but rather has characteristics typical of a
      waveguide. The strikingly large polarization anisotropy is due to the huge
      dielectric contrast but not to a photonic bandgap.

PMID- 18066310
TI  - Optical seizing and merging of voids in silica glass with infrared femtosecond
      laser pulses.
AB  - We demonstrate that one can seize and translate voids formed by IR femtosecond
      laser pulses inside silica glass and can also cause two voids to merge into one.
      We also present clear evidence of a void and its surrounding region by showing
      scanning electron microscope images of cleaved voids, which we produced by
      cleaving through the glass along a plane that included a thin laser-ablated line
      on the surface of the glass and the voids formed inside.

PMID- 18066311
TI  - Method for single-shot measurement of the carrier envelope phase of a few-cycle
      laser pulse.
AB  - The interference between different harmonics of a few-cycle optical pulse in the
      region of the spectral overlap is sensitive to the phase of the optical carrier
      inside the pulse envelope. Near-surface third-harmonic generation from Si(001)
      combined with second-harmonic generation in a 10-mum -thick beta-barium borate
      crystal produces sufficiently strong harmonic emission for single-shot
      measurement. We propose using this technique to measure the carrier envelope
      phase of high-energy 5-fs pulses.

PMID- 18066312
TI  - Precision phase control of an ultrawide-bandwidth femtosecond laser: a network of
      ultrastable frequency marks across the visible spectrum.
AB  - We demonstrate that the stability of the current optical frequency comb generated
      by a Kerr-lens mode-locked femtosecond laser is limited by the microwave
      reference used for phase locking the comb spacing. Hence we implement precision
      frequency/phase control of the entire comb to the fundamental and second-harmonic
      frequencies of a stable cw laser without any external microwave reference. The
      stability of a cw iodine-stabilized laser is transferred to millions of comb
      lines (with an instability of 3 x 10(-13)) covering more than one octave of the
      optical frequency spectrum. In addition, the mode spacing of the comb can be used
      as a stable microwave frequency derived directly from a stable optical
      oscillator.

PMID- 18066313
TI  - Properties of the pulse train generated by repetition-rate-doubling rational
      harmonic actively mode-locked Er-doped fiber lasers: errata.

PMID- 18066314
TI  - Hybrid curvature and gradient wave-front sensor.
AB  - A new wave-front sensor for adaptive optics that gives signals for the curvature
      and the two gradient components of the wave front simultaneously is proposed. The
      sensor uses quad cells placed at the foci of an array of astigmatic lenslets,
      giving three intensity-normalized differential signals. The parameters of a
      single subdetector are optimized to maximize the curvature signal. The
      performance of such a sensor designed for a membrane curvature mirror is
      analyzed. The good match between sensor and mirror is exhibited by an almost
      diagonal response matrix between the mirror actuator controls and the curvature
      signals.

PMID- 18066315
TI  - Wide-field-angle behavior of blazed-binary gratings in the resonance domain.
AB  - Blazed-binary gratings for which a blazed effect with binary etches is achieved
      under normal incidence offer first-order diffraction efficiencies larger than
      those of blazed-echelette gratings in the resonance domain [Opt. Lett. 23 1081
      (1998)]. We provide further insight into the behavior of blazed-binary gratings
      and show that they operate efficiently under symmetrical mounting and over a wide
      field-angle interval. These properties are illustrated with theoretical and
      experimental results obtained for an approximately 1000-line/mm grating at 633
      nm.

PMID- 18066316
TI  - High-frequency Bragg gratings in a photothermorefractive glass.
AB  - Holographic UV mirrors were recorded in a volume of photothermorefractive glass.
      This photosensitive silicate glass doped with silver, cerium, and fluorine is
      transparent in the near-UV, visible, and near-IR spectral regions, and its
      induced refractive-index change reaches 10(-3). UV radiation of a He-Cd laser at
      325 nm was used for Bragg grating recording with a spatial frequency of
      approximately 9200 mm(-1). The absolute diffraction efficiency of the recorded
      mirror reached 12.6% at 325 nm and did not deteriorate under the long-time
      effects of optical irradiation and heating up 400 degrees C.

PMID- 18066317
TI  - High-resolution confocal detection of nanometric displacement by use of a 2 x 1
      optical fiber coupler.
AB  - A novel high-resolution confocal measurement of nanometric displacement that uses
      a simple 2 x 1 optical fiber coupler is presented. The basic principle is to
      detect interferometrically the change in the phase difference between two
      adjacent input fibers of the coupler that results from the nonuniform wave-front
      curvature of the reflected light. Measurement of subnanometer axial modulation,
      which permits high-resolution displacement sensing by optical means, is
      demonstrated.

PMID- 18066318
TI  - Profile of a fiber from backscattering measurements.
AB  - The angular positions of the light-scattering minima obtained from structures
      placed on flat substrates are closely related to the geometry of the scattering
      object. We show how the profile of a fiber can be determined, and possible
      irregularities located, by measurement of the backscattering patterns. An
      approximate double-interaction model is used to fit the results.

PMID- 18066319
TI  - Absolute frequency stabilization of a tunable Tm:Ho:YAG laser to the HBr P(12)
      line at 2097 nm.
AB  - We demonstrate absolute frequency stabilization of a widely tunable Tm:Ho:YAG
      laser by locking the oscillator to the P(12) absorption line of the H(79)Br
      molecule at 2097.222 nm, using the fringe side-locking technique. We perform time
      and spectral analysis of open- and closed-loop error signals to evaluate the
      frequency noise. In closed-loop operation a long-term frequency stability of
      better than 2 MHz with rms frequency fluctuations of approximately 112 kHz is
      obtained over an observation time of 10(3) s.

PMID- 18066320
TI  - Polariton local states in periodic Bragg multiple-quantum-well structures.
AB  - We study analytically the optical properties of several types of defect in Bragg
      multiple-quantum-well structures. We show that a single defect leads to two local
      polariton modes in the photonic bandgap. These modes lead to peculiarities in
      reflection and transmission spectra. Detailed recommendations for experimental
      observation of the effects studied here are given.

PMID- 18066321
TI  - Multispectral imaging with a confocal microendoscope.
AB  - The concept of a multispectral confocal microscope for in vivo imaging is
      introduced. To demonstrate the concept we modified a slit-scan fluorescence
      confocal microendoscope incorporating a fiber-optic catheter for in vivo imaging
      to record multispectral images. The system was designed to examine cellular
      structures during optical biopsy and to exploit the diagnostic information
      contained within the spectral domain. Preliminary experiments were carried out in
      phantoms and cell cultures to demonstrate the potential of the technique.

PMID- 18066322
TI  - Effect of an annular pupil filter on differential confocal microscopy.
AB  - Combining differential confocal microscopy and an annular pupil filter, we
      obtained the normalized axial intensity distribution curve of an optical system.
      We used the sharp slopes of the axial response curve of the optical system to
      measure the surface profile of a reflection grating. Experimental results prove
      that this method can extend the axial dynamic range and improve the transverse
      resolution of three-dimensional profilometry by sacrificing axial resolution.

PMID- 18066323
TI  - Tunable terahertz-wave generation from DAST crystal by dual signal-wave
      parametric oscillation of periodically poled lithium niobate.
AB  - The first known demonstration of tunable terahertz-wave generation by difference
      frequency generation of dual signal-wave quasi-phase-matched optical parametric
      oscillation was performed with periodically poled LiNbO(3) (PPLN) with a series
      of gratings. An organic ionic salt, 4-dimethylamino-N-methyl-4-stilbazolium
      tosylate (DAST), was used as a nonlinear crystal. A compact terahertz-wave source
      resulted, and changing the temperature of the PPLN permitted the wavelength to be
      varied from 120 to 160 microm. The wavelength could be tuned from 100 to 700
      microm by proper selection of combinations of periodically poled gratings.

PMID- 18066324
TI  - Self-guiding multimode interference threshold switch.
AB  - We propose a new passive optical thresholding device that combines the principles
      of multimode interference (MMI) with self-guiding. The multimode region is
      composed of a nonlinear optical material that will support a self-guided beam
      (i.e., a material with a positive Kerr nonlinearity). The device operates by
      switching between the MMI mode of operation and the self-guiding mode of
      operation, depending on the input light intensity. We describe the basic
      principles of a self-guiding MMI device, simulate the device, and discuss design
      issues associated with these optically controlled optical switches.

PMID- 18066325
TI  - Optical parametric processes in isotropic third-order nonlinear media with
      magneto-optic properties.
AB  - Optical parametric interaction in isotropic third-order nonlinear media with
      magneto-optic properties is investigated. It is shown that new phase-matching
      conditions with a magneto-optic contribution are possible. In particular, we
      study four-wave mixing and electric field-induced three-wave parametric processes
      in the presence of a magnetic field applied along the direction of propagation of
      the interacting waves. Control of the new phase-matching branches can be achieved
      by tuning of the magnetic field.

PMID- 18066326
TI  - Nondestructive method for characterization of the second-order nonlinear profile
      and charge distribution in thermally poled fused silica.
AB  - Noncollinear frequency conversion of two femtosecond pulses is used to
      characterize the nonlinear profile induced in thermally poled fused silica. This
      technique permits one to deduce the nonlinear profile and the charge distribution
      induced by the poling treatment. These data and the current that passes through
      the sample during the poling are consistent with the occurrence of a built-in
      electric field associated with the diffusion of two ionic species.

PMID- 18066327
TI  - Astigmatic coherence sensor for digital imaging.
AB  - We present a novel sensor that measures the entire spatial coherence function
      within an aperture by use of a variable astigmatic lens. This sensor permits
      digital capture and processing of partially coherent fields. We demonstrate the
      sensor by sampling and computing the coherent modes of a three-dimensional
      incoherent source.

PMID- 18066328
TI  - Absolute frequency measurement of the In+ clock transition with a mode-locked
      laser.
AB  - The absolute frequency of the In(+) 5s(2) (1)S(0)5s5p (3)P(0) clock transition at
      237 nm was measured with an accuracy of 1.8 parts in 10(13). Using a phase
      coherent frequency chain, we compared the (1)S(0)(3)P(0) transition with a
      methane-stabilized HeNe laser at 3.39 microm, which was calibrated against an
      atomic cesium fountain clock. A frequency gap of 37 THz at the fourth harmonic of
      the HeNe standard was bridged by a frequency comb generated by a mode-locked
      femtosecond laser. The frequency of the In(+) clock transition was found to be
      1,267,402,452,899.92 (0.23) kHz, the accuracy being limited by the uncertainty of
      the HeNe laser reference. This result represents an improvement in accuracy of
      more than 2 orders of magnitude over previous measurements of the line and now
      stands as what is to our knowledge the most accurate measurement of an optical
      transition in a single ion.s.

PMID- 18066329
TI  - Cavity-linewidth narrowing by means of electromagnetically induced transparency.
AB  - Cavity-linewidth narrowing in a ring cavity that is due to the high dispersion
      and reduced absorption produced by electromagnetically induced transparency (EIT)
      in rubidium-atom vapor has been experimentally observed. The cavity linewidth
      with rubidium atoms under EIT conditions can be significantly narrowed. Cavity
      linewidth narrowing was measured as a function of coupling beam power.

PMID- 18066330
TI  - Frequency doubling of femtosecond pulses in walk-off-compensated N-(4
      nitrophenyl)-L-prolinol.
AB  - We show how to exploit the high quadratic nonlinear coefficient of the organic
      crystal N-(4-nitrophenyl)-L-prolinol for generation and parametric mixing of
      ultrashort pulses by use of tilted-pulse techniques. The effective crystal length
      for subpicosecond operation is shown to be enhanced from tens of micrometers to
      tens of millimeters. Efficient frequency doubling of 100-fs pulses is predicted
      in walk-off-compensated geometries with peak intensities of a few megawatts per
      square centimeter.

PMID- 18066331
TI  - Intensity-noise suppression by ytterbium codoping in heavily erbium-doped fiber
      lasers with partly clustered erbium ions.
AB  - The effect of ytterbium codoping in heavily erbium-doped fibers with partly
      clustered erbium ions on the intensity noise stemming from both pump-rate and
      cavity-loss fluctuations is theoretically investigated with a modified ion
      cluster model. Numerical results indicate that low-frequency (below 1 MHz) noise
      can be greatly suppressed by ytterbium codoping.

PMID- 18066332
TI  - Resonant nonlinear intrachannel interactions in strongly dispersion-managed
      transmission systems.
AB  - Nonlinear intrachannel interactions in a transmission system with strong periodic
      dispersion management are studied. The ghost pulse at the zero bit is shown to
      grow resonantly as a result of periodic forcing and temporal phase matching with
      the signal pulses. The growth rate depends on the degree of overlap between the
      signals. The analysis agrees with direct numerical simulation of the full system.
      Growth rates for various bit patterns as a function of map strength are obtained.

PMID- 18066333
TI  - Self-similar propagation of high-power parabolic pulses in optical fiber
      amplifiers.
AB  - Self-similarity techniques are used to study pulse propagation in a normal
      dispersion optical fiber amplifier with an arbitrary longitudinal gain profile.
      Analysis of the nonlinear Schrodinger equation that describes such an amplifier
      leads to an exact solution in the high-power limit that corresponds to a linearly
      chirped parabolic pulse. The self-similar scaling of the propagating pulse in the
      amplifier is found to be determined by the functional form of the gain profile,
      and the solution is confirmed by numerical simulations. The implications for
      achieving chirp-free pulses after compression of the amplifier output are
      discussed.

PMID- 18066334
TI  - Asymptotic analysis of Bragg fibers.
AB  - Using an asymptotic analysis, we obtain an eigenvalue equation for the general
      mode dispersion in Bragg fibers. The asymptotic analysis is applied to calculate
      the dispersion relation and the field distribution of TE modes in a Bragg fiber.
      We compare the asymptotic results with exact solutions and find excellent
      agreement between them. This asymptotic approach greatly simplifies the analysis
      and design of Bragg fibers.

PMID- 18066335
TI  - Chalcogenide-glass microlenses attached to optical-fiber end surfaces.
AB  - Convex microlenses of As(2)S(3) glass have been fabricated on oxide-glass fiber
      ends by use of a photolithographic technique. As(2)S(3) film evaporated on the
      end surface of an optical fiber is exposed to light through the opposite end
      surface, and the film etching is observed under a microscope. This process
      produces a lens that is automatically positioned on the fiber core. The As(2)S(3)
      film possesses a high refractive index, which is favorable for production of
      microlenses with short focal lengths of ~10 mum.

PMID- 18066336
TI  - Acousto-optic scanning system with very fast nonlinear scans.
AB  - A very fast (>100 kHz) acousto-optic scanning system, which relies on two
      counterpropagating acoustic waves with the same frequency modulation, is proposed
      and experimentally demonstrated. This scheme completely suppresses linear
      frequency chirp and thus permits very fast nonlinear scans and nonconstant linear
      scans. By changing the phase between the modulating signals, this scheme also
      provides very fast longitudinal scans of the focal point.

PMID- 18066337
TI  - Solgel-derived photosensitive germanosilicate glass monoliths.
AB  - We demonstrate volume gratings written in solgel-derived, Ge-doped silica
      monoliths. Glass was fabricated both with and without germanium oxygen deficient
      center (GODC) defects. The UV absorption and UV-induced index changes of these
      glasses, with and without hydrogen loading, are reported. The presence of GODC
      defects greatly enhances the photosensitivity of Ge-doped silica with and without
      the presence of hydrogen.

PMID- 18066338
TI  - Molecular vibration imaging in the fingerprint region by use of coherent anti
      Stokes Raman scattering microscopy with a collinear configuration.
AB  - We have developed a new coherent anti-Stokes Raman scattering (CARS) microscopy
      system with a collinear configuration for use in the fingerprint region. The
      system consists of a picosecond laser system and a transmission-type laser
      scanning microscope without a pinhole in front of the detector. The observable
      Raman-shift region is 900-1750 cm(-1), the spectral resolution is 30cm(-1), and
      the spatial resolution is smaller than 1 mum in the lateral direction and 3.2 mum
      in the depth direction, with objectives with a numerical aperture of 0.65. CARS
      spectra and images of polystyrene beads are demonstrated, and CARS imaging of a
      viable yeast cell is attempted.

PMID- 18066339
TI  - Semivectorial H-field analysis of rib waveguides by a modified beam-propagation
      method based on the generalized Douglas scheme.
AB  - A low-truncation-error scheme for a step-index profile is applied to analysis of
      a three-dimensional waveguide with the aid of the alternating-direction implicit
      method. The propagation constants of a single and a coupled rib waveguide are
      analyzed by use of the imaginary distance procedure. A fast convergence rate,
      which is not obtainable with the conventional second-order schemes, is realized,
      leading to highly accurate evaluation of the coupling length. A reduction in
      discretization error is also demonstrated in the beam-propagation analysis of a
      tilted rib-waveguide coupler.

PMID- 18066340
TI  - Single-longitudinal-mode operation of a grating-based fiber-ring laser using self
      injection feedback.
AB  - A fiber Bragg grating- (FBG-) based fiber-ring laser that utilizes the
      transmitted light of the FBG as self-injection feedback for single-longitudinal
      mode (SLM) oscillation is proposed and demonstrated. This laser is simply
      constructed by means of feeding back the transmitted light of the FBG and is
      coupled into the main ring cavity through an optical coupler. The self-injection
      feedback is the key to ensuring SLM laser oscillation. The SLM operation
      principle is discussed in detail, and a SLM laser with output power of 6.6 dBm,
      an optical signal-to-noise ratio of 57 dB at 1549.19 nm, and a short-term
      linewidth of 3.5 kHz is reported.

PMID- 18066341
TI  - Transport-based image reconstruction in turbid media with small source-detector
      separations.
AB  - We demonstrate a new method for imaging through several millimeters of a turbid
      sample with a resolution of approximately 100 mum by combining aspects of
      confocal reflectance microscopy and diffuse optical tomography. By laterally
      displacing the pinhole aperture of a confocal microscope we can achieve small
      source-detector separations and detect minimally scattered light. A
      reconstruction algorithm based on the first Born approximation to the radiative
      transport equation is then used to reconstruct an image of a 100-mum absorbing
      object located 2 mm beneath the surface.

PMID- 18066342
TI  - Fiber-optic confocal microscopy using a spatial light modulator.
AB  - We present a novel fiber-optic confocal microscope in which the scanning
      operation is achieved by use of a spatial light modulator (SLM) to sequentially
      illuminate individual fibers or patterns of multiple fibers. Experimental images
      are presented, and the optical-sectioning capability of the device is
      demonstrated. The novel SLM-based system is more optically efficient, achieves
      higher contrast, and has improved optical-sectioning capabilities compared with
      those of other proposed instruments for confocal microendoscopy.

PMID- 18066343
TI  - Optical parametric generation in 2-mum-wavelength-pumped periodically poled
      LiNbO(3).
AB  - An optical parametric generator based on periodically poled LiNbO(3) and pumped
      by a 2.051-mum-wavelength laser has been demonstrated. Pump pulses of 50-ns
      duration of 50-Hz repetition frequency were converted into signal and idler
      pulses in the 3.4-5.2-mum wavelength range in a double-pass pump configuration by
      a 5-cm-long quasi-phase-matched crystal. An average pump power of 180 mW
      generated 30-mW average signal power at 3.64-mum wavelength, corresponding to
      16.7% signal conversion efficiency.

PMID- 18066344
TI  - Spatial modulational instability in one-dimensional lithium niobate slab
      waveguides.
AB  - We report an experimental study of the breakup through modulational instability
      of broad fundamental beams near the phase-matching condition for second-harmonic
      generation in lithium niobate slab waveguides. Two mechanisms for initiating
      modulational instability, waveguide imperfections and noise on the input beam,
      are identified.

PMID- 18066345
TI  - Enhanced robustness of dispersion-managed solitons with respect to polarization
      mode dispersion.
AB  - Polarization mode dispersion causes solitons to emit background radiation, which
      degrades transmission quality. It is shown theoretically and confirmed by
      numerical simulations that dispersion-managed solitons can trap part of that
      radiation into localized eigenmodes, thus yielding improvement in transmission
      quality compared with that of conventional solitons.

PMID- 18066346
TI  - Scalar field of nonparaxial Gaussian beams.
AB  - A family of closed-form expressions for the scalar field of strongly focused
      Gaussian beams in oblate spheroidal coordinates is given. The solutions satisfy
      the wave equation and are free from singularities. The lowest-order solution in
      the far field closely matches the energy density produced by a sine-condition,
      high-aperture lens illuminated by a paraxial Gaussian beam. At the large waist
      limit the solution reduces to the paraxial Gaussian beam form. The solution is
      equivalent to the spherical wave of a combined complex point source and sink but
      has the advantage of being more directly interpretatable.

PMID- 18066347
TI  - Timing jitter in a kilohertz regenerative amplifier of a femtosecond-pulse
      Ti:Al(2)O(3) laser.
AB  - We measure the timing error of femtosecond pulses amplified by a Ti:sapphire
      regenerative amplifier at a 1-kHz repetition rate by use of a modified cross
      correlation technique. Linearly frequency-chirped amplified pulses are frequency
      mixed with transform-limited oscillator pulses. A shift in the sum frequency
      corresponds to the timing error of each amplified pulse relative to the
      oscillator pulses. The timing error was measured every 6 ms with approximately 1
      fs resolution over a measurable range of 400 fs.

PMID- 18066348
TI  - Noise suppression in femtosecond mid-infrared light sources.
AB  - An experimental and theoretical study of intrinsic correlations and noise
      suppression mechanisms in two-stage femtosecond mid-IR light sources is
      presented. The setup, based on parametric amplification in BBO and subsequent
      difference-frequency mixing in AgGaS(2), delivers approximately 100-fs mid-IR
      pulses with 1-2-muJ energy. Exceptionally low pulse-energy fluctuations of only
      0.2% in the mid-IR (lambda approximately 3-6 mum) are found, which are much
      smaller than the Ti:sapphire amplifer noise. The noise suppression is analyzed
      and found to stem from the interplay between dispersion and pump depletion.

PMID- 18066349
TI  - Unbalanced third-order correlations for full characterization of femtosecond
      pulses.
AB  - Phase and intensity from correlation and spectrum only (PICASO) is a simple and
      accurate method for fully characterizing femtosecond pulses. We extend this
      technique to make use of third-order intensity correlations. Unbalancing the
      interferometer makes the retrieval algorithm sensitive to the direction of time
      and improves the retrieval of certain pulse shapes. We investigate the
      sensitivity of the retrieval to direction of time as a function of the degree of
      imbalance in the correlator.

PMID- 18066350
TI  - High-resolution retinal images obtained by deconvolution from wave-front sensing.
AB  - A new concept for high-resolution ophthalmoscopy is presented. The method is an
      alternative to the use of adaptive optics. It is based in deconvolving a retinal
      image from simultaneously acquired multiple ocular wave-front aberration and
      aberration-distorted fundus images. A computer simulation of the procedure using
      actual ocular wave-front aberration data that shows the validity of the method is
      first presented. Experimental results obtained from an artificial eye serve both
      to probe the method in a situation similar to the real eye and to introduce the
      required preprocessing of the retinal images. Finally, results from a real human
      retina are presented, and the potential of the technique is discussed.

PMID- 18066351
TI  - Assessing the effects of the HIPAA privacy rule on release of patient information
      by healthcare facilities.
AB  - The HIPAA privacy rule (HIPAA) has had both positive and negative effects on the
      release of patient information by healthcare facilities. Although the intention
      of HIPAA was to protect patient privacy and to promote security and
      confidentiality of patient information, it has had unintended consequences for
      facilities. To identify some of these unintended effects, two expert panels of
      health information management directors from healthcare facilities participated
      in the nominal group technique meetings. They identified 70 barriers related to
      release of patient information associated with the implementation of HIPAA. The
      perceived biggest barriers were increases in the public's misunderstanding about
      release of patient information, lack of an umbrella policy or regulation defining
      infractions and enforcement that allows individual institutions to make their own
      interpretations, and challenges to health information management professionals in
      controlling safeguards related to release of information given the transition to
      electronic health records and the increased involvement of information
      technology. The findings from this study suggest there is a need for additional
      clarification of the regulations governing HIPAA, standardized instructions, and
      extensive training of healthcare workers.

PMID- 18066352
TI  - What mapping and modeling means to the HIM professional.

PMID- 18066353
TI  - Coding for quality measurement: the relationship between hospital structural
      characteristics and coding accuracy from the perspective of quality measurement.
AB  - This study examines the relationship between hospital structural characteristics
      and coding accuracy from the perspective of quality measurement. To measure
      coding accuracy for quality measurement, the study utilizes the "present on
      admission" indicator, a data element in the New York state hospital
      administrative database. This data element is used by hospitals across New York
      state to indicate if a particular secondary diagnosis is "present on admission,"
      "not present on admission," or "uncertain." Since the accurate distinction
      between comorbidities (present at admission) and complications (not present at
      admission,) is critical for risk adjustment in comparative hospital quality
      reports, this study uses the occurrence of the value "uncertain" in the "present
      on admission" indicator as the primary measure of coding accuracy. A lower
      occurrence of the value "uncertain" is considered to be reflective of better
      coding accuracy. Moreover, since coding accuracy of the "present on admission"
      indicator links back to the accuracy of physician documentation, a focus on the
      occurrence of the value "uncertain," also helps gain insight into physician
      documentation efficacy within the facility. By utilizing this approach,
      therefore, the study serves the twin purpose of 1) addressing the gap in the
      literature with respect to large-scale studies of "coding for quality," and 2)
      providing insight into the structural characteristics of institutions that are
      likely facing organizational challenges of physician documentation from the
      perspective of quality measurement.

PMID- 18066354
TI  - Managing multiple projects: a literature review of setting priorities and a pilot
      survey of healthcare researchers in an academic setting.
AB  - OBJECTIVES: To summarize and then assess with a pilot study the use of published
      best practice recommendations for priority setting during management of multiple
      healthcare research projects, in a resource-constrained environment. METHODS:
      Medical, economic, business, and operations literature was reviewed to summarize
      and develop a survey to assess best practices for managing multiple projects.
      Fifteen senior healthcare research project managers, directors, and faculty at an
      urban academic institution were surveyed to determine most commonly used priority
      rules, ranking of rules, characteristics of their projects, and availability of
      resources. Survey results were compared to literature recommendations to
      determine use of best practices. RESULTS: Seven priority-setting rules were
      identified for managing multiple projects. Recommendations on assigning
      priorities by project characteristics are presented. In the pilot study, a large
      majority of survey respondents follow best practice recommendations identified in
      the research literature. However, priority rules such as Most Total Successors
      (MTS) and Resource Scheduling Method (RSM) were used "very often" by half of the
      respondents when better performing priority rules were available. CONCLUSIONS:
      Through experience, project managers learn to manage multiple projects under
      resource constraints. Best practice literature can assist project managers in
      priority setting by recommending the most appropriate priority given resource
      constraints and project characteristics. There is room for improvement in
      managing multiple projects.

PMID- 18066355
TI  - Protective measures for private health information.
AB  - This study measured attitudes about patient privacy. Participants ranked a
      collection of 25 patient- specific health information protection measures that
      have been established as a part of the Health Insurance Portability and
      Accountability Act (HIPAA), effective in April 2003. Individual points of view
      were surveyed to determine which information protection measures patients felt to
      be least effective and most effective with regard to protection of patient
      privacy. The researcher, being interested in subjects with the human immuno
      deficiency virus (HIV), conducted an exploratory Q-Methodology study to capture
      individual participants' points of view. A by-person factor analysis was
      performed on the intercorrelated Q-sort matrix. The subjects clustered into three
      groups; however, the concern for privacy was similar for subjects with and
      without HIV. Recommendations for policy changes are discussed for four areas:
      usage of the "Notice of Privacy Practices," patient sign-in procedures, the role
      of the privacy officer, and staff education.

PMID- 18066356
TI  - The effectiveness of ICD-10-CM in capturing public health diseases.
AB  - This research study examined the usefulness of the ICD-10-CM system in capturing
      public health diseases (reportable diseases or the nationally notifiable
      infectious diseases, leading causes of death, and morbidity/mortality related to
      terrorism), when compared to ICD-9-CM.1-3 It also examined agreement levels of
      coders when coding public health diseases in both ICD-10-CM and ICD-9-CM. Overall
      results demonstrate that ICD-10-CM is more specific and fully captures more of
      the public health diseases examined than ICD-9-CM. In the analysis of all the
      public health diseases, such as reportable diseases (p<0.001), top 10 causes of
      death (p<0.001), and those related to terrorism (p<0.001), it was found that the
      overall rankings for disease capture for ICD-10-CM were significantly higher than
      the rankings for ICD-9-CM. When examining whether diseases were captured more
      straightforwardly and clearly (regarding agreement levels) between coding
      systems, statistically significant differences were found for external causes of
      injury (p<0.001), diabetes (average rank only, p<0.05), lower respiratory disease
      (p<0.001), heart disease (p<0.001), and malignant neoplasms (p<0.05). Although
      this result may be due to the coder's higher level of experience with ICD-9-CM,
      it also points to the potential need for more specific coding education and
      practice with the ICD-10-CM system.

PMID- 18066357
TI  - Evaluation and management documentation and coding technology adoption.
AB  - This study determines the relative effect of financial incentives, practice
      characteristics, and regulatory guidelines on the utilization of documentation
      and coding technology among physician practices employing HIM professionals. A
      total of 442 HIM professionals, 9.78 percent of the surveyed population,
      completed a Web-based survey regarding their practices and E/M documentation and
      coding methods used. More physician practices use the traditional documentation
      and coding methods than use automated methods. Less than half of the practices
      using automated documentation technology also utilized automated coding
      technology. Financial incentives and regulatory guidelines were not related to
      documentation or coding method used. Organization size and type were highly
      related to documentation or coding method used. Practices using coding technology
      were more likely to perform coding validation. The reasons for low levels of
      coding technology adoption, which requires little additional physician effort,
      suggest the potential presence of unique factors inhibiting the adoption of this
      technology.

PMID- 18066358
TI  - Leadership frames and perceptions of effectiveness among health information
      management program directors.
AB  - Leadership is important to health science education. For program effectiveness,
      directors should possess leadership skills to appropriately lead and manage their
      departments. Therefore, it is important to explore the leadership styles of
      programs' leaders as health science education is undergoing reform. Program
      directors of two and four-year health information management programs were
      surveyed to determine leadership styles. The study examined leadership styles or
      frames, the number of leadership frames employed by directors, and the
      relationship between leadership frames and their perceptions of their
      effectiveness as a manager and as a leader. The study shows that program
      directors are confident of their human resource and structural skills and less
      sure of the political and symbolic skills required of leaders. These skills in
      turn are correlated with their self-perceived effectiveness as managers and
      leaders. Findings from the study may assist program directors in their career
      development and expansion of health information management programs as a
      discipline within the health science field. As academic health centers receive
      greater pressure from the Institute of Medicine and accrediting agencies to
      reform health science education, the question of leadership arises. These centers
      have taken a leadership role in reforming health professional education by
      partnering with educational institutions to improve the health of communities. To
      achieve health education reform, health sciences educators must apply effective
      leadership skills.1 College and university leadership is challenged on how to
      best approach educational reform across health science fields. This article
      discusses leadership styles employed by program directors of one health science
      department, health information management, in directing programs for health
      science education reform.

PMID- 18066359
TI  - Enhancement of achievement and attitudes toward learning of allied health
      students presented with traditional versus learning-style instruction on
      medical/legal issues of healthcare.

PMID- 18066360
TI  - Formative evaluation using checklists to improve research proposals.
AB  - Developing research proposals that protect human participants and understanding
      the institutional review board (IRB) approval process require high-level
      application of many skills. The purpose of this article is to describe how
      faculty can use formative evaluation techniques and checklists to guide students
      to build skills in writing research proposals for studies that involve human
      participants or their data. Formative evaluation, the process of critically
      reviewing work to improve it, is emphasized, and checklists that summarize IRB
      criteria and standards and present the critical content of research proposals for
      studies involving human participants are provided. Teaching principles that can
      guide faculty in using the checklists to give feedback and help students develop
      high-quality research proposals are discussed.

PMID- 18066361
TI  - Self-care communication during medical encounters: implications for future
      electronic medical records.
AB  - OBJECTIVE: The growing importance of electronic medical records (EMRs) to
      healthcare systems is evident, yet the debate concerning their impact on patient
      provider communication during encounters remains unresolved. For this study, we
      hypothesize that providers' use of the EMR will improve patient-provider
      communication concerning self-care during the medical encounter. DESIGN: Cross
      sectional, observational study. SETTING: A primary-care outpatient clinic of the
      South Texas Veterans Health Care System in San Antonio, TX, USA. METHODS: A
      convenience sample of 50 patient/physician encounters was videotaped, transcribed
      verbatim, and analyzed to determine the time that the physician spent using the
      EMR and self-care topics discussed. Self-care topics included medication use,
      recognition of disease symptoms, diet, exercise, management of physical and
      emotional distress, self-monitoring activities, cigarette smoking, alcohol
      consumption, and family support/community resources. Two observers independently
      coded for the kind of self-care topics (kappa = 0.91) using the Atlas.ti software
      package. RESULTS: Encounters averaged 22.6 minutes (range: 5-47, SD = 8.9). We
      identified two encounter types based on EMR usage: low use (n = 13), with EMR use
      of two minutes or less, and moderate to high EMR use (n = 37), with EMR use of
      five minutes or more. Average time for encounters was 25 minutes for moderate to
      high EMR use encounters and 16 minutes for low EMR use encounters (t test, p <
      0.001). Issues pertaining to facets of self-care management were discussed in
      every physician-patient interaction (100 percent). The most frequently discussed
      self-care topics were medication use (100 percent), physical distress (76
      percent), and disease symptoms (76 percent). Self-monitoring activities,
      exercise, and diet were discussed in 62 percent, 60 percent, and 46 percent of
      the 50 encounters respectively. Emotional distress (26 percent), smoking (30
      percent), family support/community resources (26 percent), and alcohol
      consumption (20 percent) were the least discussed issues. Encounters were similar
      with respect to the kinds of self-care elements discussed. However, EMR use
      encounters were more likely to include a higher number of self-care topics raised
      by physicians than low EMR use encounters, particularly on disease symptoms (odds
      ratio = 4.4, p = 0.05), and physical distress (odds ratio = 7.4, p = 0.006). A
      significant correlation was observed between the number of self-care elements
      discussed and time spent on the EMR (r = 0.6, p < 0.05), but no correlation was
      observed between the length of the encounter and self-care discussion (r = 0.009,
      p = 0.90). CONCLUSIONS: The use of an EMR during encounters is associated with an
      increase in the number of self-care topics raised by physicians. EMRs offer the
      opportunity to involve patients and physicians in discussion of self-care during
      patients' visits. Given the current emphasis on the widespread implementation of
      EMRs, future EMRs should be designed to systematically facilitate the integration
      of EMRs into clinical exchanges about self-care.

PMID- 18066362
TI  - A new model for the organizational structure of medical record departments in
      hospitals in Iran.
AB  - The organizational structure of medical record departments in Iran is not
      appropriate for the efficient management of healthcare information. In addition,
      there is no strong information management division to provide comprehensive
      information management services in hospitals in Iran. Therefore, a suggested
      model was designed based on four main axes: 1) specifications of a Health
      Information Management Division, 2) specifications of a Healthcare Information
      Management Department, 3) the functions of the Healthcare Information Management
      Department, and 4) the units of the Healthcare Information Management Department.
      The validity of the model was determined through use of the Delphi technique. The
      results of the validation process show that the majority of experts agree with
      the model and consider it to be appropriate and applicable for hospitals in Iran.
      The model is therefore recommended for hospitals in Iran.

PMID- 18066363
TI  - Risks, barriers, and benefits of EHR systems: a comparative study based on size
      of hospital.
AB  - With the government backing the concept of electronic health records (EHR), and
      with technology being used in every walk of life, more and more hospitals are
      looking into implementing EHR systems. A national survey of U.S. hospitals was
      conducted in February/March 2005 to identify the status of EHR systems in
      hospitals regarding the core functionalities implemented (as identified by the
      Institute of Medicine), and to determine the perceived benefits, risks, and
      barriers to adoption of EHR systems in relation to the size of the hospital. The
      results showed that 37 percent of the hospitals that participated had some
      components in all of the core functionalities of an EHR system, while 27 percent
      were using at least some of the core functionalities. There was a significant
      relationship in some of the perceived benefits and barriers to adoption of EHR
      systems based on the size of the hospital. With regard to perceived benefits, a
      large correlation was found between the "medical staff's work efficiency and time
      management" and size of the hospital. As to perceived barriers to adoption, the
      cost of hardware and the size of the hospital were interwoven.

PMID- 18066364
TI  - Assessment of student outcomes in undergraduate health information administration
      programs.
AB  - The purpose of this research was to a) determine what assessment methods are
      being used in undergraduate health information administration programs to assess
      student learning and the usefulness of those methods, b) determine to what extent
      programs have incorporated good student learning assessment practices. Programs
      use a variety of assessment tools to measure student learning; the most useful
      include assessments by the professional practice supervisor, course tests,
      assignments, presentations, capstone experiences, comprehensive projects,
      analyses of the students' academic progress, and the results of the RHIA
      credentialing examination. The greatest challenge for using the results of
      student outcomes assessment is making changes in a timely manner. Satisfying
      accreditation requirements and program improvements were identified as the
      primary reasons for doing outcomes assessments. The results signify a need to
      increase program directors' knowledge regarding the essentials of outcomes
      assessment.

PMID- 18066365
TI  - Can factors related to self-regulated learning and epistemological beliefs
      predict learning achievement in undergraduate asynchronous Web-based courses?
AB  - This study examined the effects of self-regulated learning (SRL) and
      epistemological beliefs (EB) on individual learner levels of academic achievement
      in Web-based learning environments while holding constant the effect of computer
      self-efficacy, reason for taking an online course, and prior college academic
      achievement. The study constituents included 201 undergraduate students enrolled
      in a variety of asynchronous Web-based courses at a university in the
      southeastern United States. Data was collected via a Web-based questionnaire and
      subjected to the following analyses: separate exploratory factor analyses of the
      self-regulated learning and the epistemological beliefs question items,
      correlations between the independent variables and the dependent variable, and
      linear regression of final course grades with all the variables in the model.
      Analysis of the data revealed that three independent variables (GPA, Expectancy,
      and GPA_Exp) were significant predictors in the model of learning achievement in
      asynchronous online courses. Discussion of the study's predictive model follows.

PMID- 18066366
TI  - How secure is your information system? An investigation into actual healthcare
      worker password practices.
AB  - For most healthcare information systems, passwords are the first line of defense
      in keeping patient and administrative records private and secure. However, this
      defense is only as strong as the passwords employees chose to use. A weak or
      easily guessed password is like an open door to the medical records room,
      allowing unauthorized access to sensitive information. In this paper, we present
      the results of a study of actual healthcare workers' password practices. In
      general, the vast majority of these passwords have significant security problems
      on several dimensions. Implications for healthcare professionals are discussed.

PMID- 18066367
TI  - Identifying barriers to the adoption of new technology in rural hospitals: a case
      report.
AB  - The purpose of this study is to identify barriers to the adoption of new
      technology in rural settings. Specifically, this paper focuses on identifying and
      overcoming barriers to the adoption of a medication error reporting system in
      eight rural hospitals. Prior research has generally focused on barriers to the
      adoption of new technology in urban areas, medical centers, or large hospitals.
      The literature has identified six primary barriers to the adoption of new
      technology: cost, legality, time, fear, usefulness, and complexity. Although our
      research recognizes these same barriers, the means through which these barriers
      may be mitigated are different in rural settings. Our research identified three
      additional barriers to the adoption of new technology that may be specific to
      rural areas: personnel, physical space, and Internet access. Our outcome
      variable, in order to demonstrate our success, is the number of reported
      medication errors.

PMID- 18066368
TI  - Patient health information management: searching for the right model.
AB  - Accurate and timely health information is a crucial element in the medical
      decision making process during a medical encounter. Inadequate or misleading
      patient health information can lead to medical errors, inaccurate decision
      making, and increased cost. Providing physicians with access to every detail of a
      patient's medical history is difficult. Striking the balance between adequate and
      effective amounts of information is difficult. The Personal Health Record and
      Continuity of Care Record have emerged as concepts to support that balance. This
      paper reviews recently published literature on (1) approaches to personal health
      information management, (2) distinctions between terms and definitions describing
      patient health information, its format, its availability, and its accessibility,
      (3) guidelines, studies, or standards to support the rationale of patient
      information data elements that should be available to the provider for any
      medical encounter, and (4) identification of the most important needs for patient
      health information that should be addressed. The purpose of the review is to
      clarify the benefits and detriments of the different approaches as well as to
      provide some recommendations for the right model of patient health information
      management, focusing on the idea of the appropriate health information being
      available when needed.

PMID- 18066369
TI  - Recruitment: making our efforts count.
AB  - Over the last decade, enrollments in health information technology and health
      information administration programs have spiraled downward resulting in the
      closure of programs. Reversing this trend is imperative for the survival of the
      health information management profession. This research study looked at: 1. how
      students learned about the HIM profession; 2. what attracted students to the
      career; 3. the most effective recruitment methods. Using data gathered from 754
      students enrolled in either a coding, health information technology, or health
      information administration program revealed: a) students learned about the
      profession through their employer, college counselors, a health information
      professional, health information management student, or family friend b) a
      variety of career options attracted students to the career c) the most effective
      recruitment method is posting flyers in healthcare organizations, colleges, and
      high schools. Research results support using a multifaceted approach to attract
      students into the program.

PMID- 18066370
TI  - Consumer informatics: elderly persons and the Internet.
AB  - This paper reports the findings from a study designed to determine whether, when
      appropriately trained, older adults would use the Internet to gather healthcare
      information and actively seek information that could directly affect their own
      treatment and care. Results show that older adults are willing to use the
      Internet to locate health information. However, familiarity with Internet-based
      healthcare resources did not lead participants to adopt significant levels of
      Internet use or change the way they participated in their own healthcare. These
      results suggest that the Internet may not have as great an influence on how
      individuals manage their healthcare, and point out the fact that seniors 65 and
      over may still cling to a paternalistic model when working with their own
      healthcare provider.

PMID- 18066371
TI  - A framework for designing a healthcare outcome data warehouse.
AB  - Many healthcare processes involve a series of patient visits or a series of
      outcomes. The modeling of outcomes associated with these types of healthcare
      processes is different from and not as well understood as the modeling of
      standard industry environments. For this reason, the typical multidimensional
      data warehouse designs that are frequently seen in other industries are often not
      a good match for data obtained from healthcare processes. Dimensional modeling is
      a data warehouse design technique that uses a data structure similar to the
      easily understood entity-relationship (ER) model but is sophisticated in that it
      supports high-performance data access. In the context of rehabilitation services,
      we implemented a slight variation of the dimensional modeling technique to make a
      data warehouse more appropriate for healthcare. One of the key aspects of
      designing a healthcare data warehouse is finding the right grain (scope) for
      different levels of analysis. We propose three levels of grain that enable the
      analysis of healthcare outcomes from highly summarized reports on episodes of
      care to fine-grained studies of progress from one treatment visit to the next.
      These grains allow the database to support multiple levels of analysis, which is
      imperative for healthcare decision making.

PMID- 18066372
TI  - Relationships between academic program variables and success on the Registered
      Health Information Administrator certification examination.
AB  - The purpose of this research study was to investigate the relationships and
      influence of selected components of health information administration (HIA)
      programs and the program's percentage of graduates passing the Registered Health
      Information Administrator (RHIA) certification examination. Pearson product
      moment correlation coefficients generated between the dependent variable and
      three independent variables yielded significant results. The regression model did
      not significantly predict a program's percentage of graduates passing the RHIA
      certification examination.

PMID- 18066373
TI  - Improving patient safety through information technology.
AB  - Health information technology (HIT) is generally accepted as the solution for the
      nation's medical error crisis. Although limited studies suggest the importance of
      using HIT in the process of medication management, research has failed to
      adequately describe how HIT actually works in capturing medication error data and
      improving patient safety within a healthcare system.1-3 The aim of our study is
      to identify essential elements in the adoption of technology within the broader
      context of system change and workflow modification. Using the adoption of an
      electronic reporting system to improve patient safety, we examine the role of
      this technology within process improvement, culture, and workflow.

PMID- 18066374
TI  - Blogging in an online health information technology class.
AB  - In this article we introduce blogs, including their brief history, their current
      status, and motivations for blogging. We describe how we created a course blog in
      one online Health information management (HIM) baccalaureate course. We describe
      three pedagogical purposes (online discussion, digital drop box, and class
      project management tool) of the course blog. We report the results of our after
      class survey on using the blog as a learning tool. Survey results illustrated
      that 55 percent of the students agree that the blog can be a tool for
      facilitating learning, 50 percent agree it can be used as a tool for student
      activities, 60 percent agree it can serve as a medium for reflective thinking and
      writing, and 60 percent want to see its application in other courses.

PMID- 18066375
TI  - ICF: representing the patient beyond a medical classification of diagnoses.
AB  - The International Classification of Functioning, Disability and Health (ICF) is a
      component essential to ensuring the collection of accurate and complete
      healthcare data that correctly reflect the care provided to individuals. In fact,
      many countries outside of the United States have found uses for ICF. While
      research continues in the United States on the potential value of implementing
      ICF, deliberations are establishing the need to implement ICF to develop
      knowledge about the physical, mental, and social functioning of patients. In the
      course of these deliberations, issues related to current data collection
      activities, the use of ICF in an electronic health record (EHR) system, training
      requirements, and terminology maps are beginning to emerge.

PMID- 18066376
TI  - Data, information, knowledge: a healthcare enterprise case study.
AB  - An efficient, integrated health services delivery enterprise requires the ability
      to coordinate service delivery across the provider network and avoid duplication
      of services. It must be able to associate relevant clinical information with
      patients regardless of which facility delivered the services. There are
      significant challenges in collecting, organizing, and extracting value from data
      collected in the course of providing healthcare. This paper follows a large urban
      public healthcare enterprise in its attempts to address some of these challenges.
      Using a case-study methodology, the paper shows how information technology (IT)
      can help a healthcare organization derive improved information and generate
      knowledge from data stored in disjoint systems.

PMID- 18066377
TI  - HIPAA compliance in U.S. hospitals: a self-report of progress toward the security
      rule.
AB  - In January 2004, a random sampling of 1,000 U.S. hospitals was surveyed by
      researchers at a midwestern university to determine perceived level of compliance
      with the security requirements of the federal Health Insurance Portability and
      Accountability Act (HIPAA). Exactly one year later, a follow-up survey was sent
      to the 286 respondents of the 2004 survey, yielding a 50 percent return rate (n =
      144). There was an overall trend in increased HIPAA security compliance from 2004
      to 2005. There was no significant difference in perceived level of compliance
      based on the size of the hospital for the majority of security standards.

PMID- 18066378
TI  - From regional healthcare information organizations to a national healthcare
      information infrastructure.
AB  - Recently there has been increased focus on the need to modernize the healthcare
      information infrastructure in the United States. The U.S. healthcare industry is
      by far the largest in the world in both absolute dollars and in percentage of GDP
      (more than $1.5 trillion, or 15 percent of GDP). It is also fragmented and
      complex. These difficulties, coupled with an antiquated infrastructure for the
      collection of and access to medical data, lead to enormous inefficiencies and
      sources of error. Consumer, regulatory, and governmental pressure drive a growing
      consensus that the time has come to modernize the U.S. healthcare information
      infrastructure (HII). While such transformation may be disruptive in the short
      term, it will, in the future, significantly improve the quality, expediency,
      efficiency, and successful delivery of healthcare while decreasing costs to
      patients and payers and improving the overall experiences of consumers and
      providers. The launch of a national health infrastructure initiative in the
      United States in May 2004--with the goal of providing an electronic health record
      for every American within the next decade--will eventually transform the
      healthcare industry in general, just as information technology (IT) has
      transformed other industries in the past. The key to this successful outcome will
      be based on the way we apply IT to healthcare data and the services delivered
      through IT. This must be accomplished in a way that protects individuals and
      allows competition but gives caregivers reliable and efficient access to the data
      required to treat patients and to improve the practice of medical science. This
      paper describes key IT solutions and technologies that address the challenges of
      creating a nation-wide healthcare IT infrastructure. Furthermore we discuss the
      emergence of new electronic healthcare services and the current efforts of IBM
      Research, Software Group, and Healthcare Life Sciences to realize this new vision
      for healthcare.

PMID- 18066379
TI  - Development of a public health assessment tool to prevent Lyme disease: tool
      construction and validation.
AB  - This study involved the design and validation of a new Lyme disease risk
      assessment instrument. The study was funded in part by a research grant from the
      American Health Information Management Association (AHIMA) Foundation on Research
      and Education (FORE). The resulting instrument measured theoretical constructs
      such as attitudes, behaviors, beliefs, skills, and knowledge relative to Lyme
      disease. The survey assessment tool is described here, and the tool development
      process, the validation and reliability process, and results are presented. The
      assessment tool was created by using a standard instrument development process
      that first involved constructing possible items (questions) based on several
      health behavior theories and known health risk behaviors. These items were then
      further refined by using focus groups, a small pilot study, factor analysis, and
      a large-scale pilot study. Validity and reliability indices were established with
      a test-retest reliability coefficient of .66, and finally the tool was used among
      a population living in a Lyme-disease-endemic area. Cronbach's alpha coefficients
      of .737 for behavioral items, .573 for cognitive items, and .331 for
      environmental items were established.

PMID- 18066380
TI  - Using MedPAR data as a measure of urinary tract infection rates: implications for
      the Medicare inpatient DRG payment system.
AB  - A valuable metric of hospital performance is the rate of nosocomial infections,
      particularly urinary tract infections (UTIs). Current measurement techniques are
      expensive to administer and are not widely available. Determining a measurement
      index of nosocomial UTI incidence using Medicare Provider Analysis and Review
      (MedPAR) data to make recommendations may better align hospital payment with
      delivery of quality healthcare. There is significant variation among hospitals'
      calculated nosocomial UTI rates. In a sample hospital, the hospital received an
      estimated $675,000 in additional payments from Medicare due to payments for
      secondary nosocomial UTIs. The Comparative MedPAR Nosocomial UTI Index is a
      meaningful tool for determining nosocomial UTI rates as a measure of hospital
      quality. Additional improvements to the tool include incorporating risk factors
      based upon initial diagnosis, Major Diagnostic Category (MDC), and other
      diagnoses. Patients would benefit if the Centers for Medicare and Medicaid
      Services (CMS) discontinued the practice of paying hospitals for hospital
      acquired infections, as this practice discourages adoption of infection-reducing
      initiatives.

PMID- 18066381
TI  - Standards for the content of the electronic health record.
AB  - A descriptive, cross-sectional study was performed to measure the awareness, use,
      and validity of the minimum content recommended in the American Society for
      Testing and Materials (ASTM) standards for content and structure of electronic
      health records. A Web-based survey was developed and used as the primary tool to
      collect this data. Data was collected from a random sample of healthcare
      facilities from across the country, vendors, and volunteers. Thirteen percent of
      respondents had an electronic health record (EHR) system fully in place while 10
      percent did not have or did not plan to have an EHR system. The majority of
      respondents (62 percent) used a vendor system for EHR development. The majority
      of respondents were not aware or slightly aware of the ASTM E1384 standards.
      Respondents believed that the minimum data elements outlined in the ASTM
      standards should be included in all EHR systems. Data items such as educational
      level, patient instructions related to disposition, problem numbers, treatment
      plan ID, provider agency ID code, and medication date of last refill should not
      always be included in EHR systems.

PMID- 18066382
TI  - Current coding competency compared to projected competency.
AB  - Coding competency is extremely important to the health information management
      (HIM) profession and healthcare in general. The research presented in this
      article evaluates coding skill and competency using practice-based research. The
      projected skill set for the clinical data specialist, the future coding role set
      forth in the publication Evolving HIM Careers, was used to determine how prepared
      current coders are in terms of projected competencies. To conduct this
      investigation, a random sample of coders and non-coders were surveyed to
      determine how well the current level of skills relate to the skills described for
      the clinical data specialist. In addition to evaluating the skills of current
      coders, non-coders were used to determine whether there was a statistically
      significant difference between coders and non-coders' skills relative to the
      future competencies. If the coders and non-coders had similar self-assessed
      skills, the validity of the skill set would be questionable. If however, the self
      assessed skill was significantly different, the assertion that the skill set is
      specific to coders would be more credible. The findings from the research suggest
      that there are many skills projected for the clinical data specialist that are
      shared by both coders and non-coders. Also, neither coders nor non-coders
      reflected the level of competence in their self-assessed skills in many areas,
      such as understanding coding and classification systems other than ICD-9 and CPT,
      designing audit tools, performing quality audits, and selecting statistical
      software applications appropriate to the data to be captured. The research also
      suggests that coding professionals who wish to prepare for the future should
      acquire more communication, research, and management skills. Further, because
      there are only a few skills that were found to be significantly different between
      the two groups, the non-coding health information professionals can prepare to
      become coding professionals by gaining skills in coding systems and reimbursement
      software. Moreover, the implication is that the skill set projected for coders
      applies to all HIM professionals as well.

PMID- 18066383
TI  - HIPAA privacy implementation issues in Pennsylvania healthcare facilities.
AB  - A 20-question survey was sent in the mail to HIM directors in Pennsylvania
      healthcare facilities to solicit feedback regarding implementation issues of the
      HIPAA privacy rule requirements. Questions focused on gathering basic demographic
      data, information on HIM involvement with the privacy rule requirements, the
      procedures whereby facilities were meeting the privacy rule requirements,
      occurrences of confidentiality breaches, and respondents' perceptions about the
      privacy rule. Findings suggested that HIM professionals continue to be involved
      with many areas of the privacy rule and have taken on new responsibilities with
      this involvement. Findings also suggested that respondents did not think the
      privacy rule would prevent future confidentiality breaches. Only half of
      respondents thought that the privacy regulations were even necessary. Many
      respondents felt their level of importance within their facility increased.

PMID- 18066384
TI  - The architecture of a modern military health information system.
AB  - This article describes a melding of a government-sponsored architecture for
      complex systems with open systems engineering architecture developed by the
      Institute for Electrical and Electronics Engineers (IEEE). Our experience in
      using these two architectures in building a complex healthcare system is
      described in this paper. The work described shows that it is possible to combine
      these two architectural frameworks in describing the systems, operational, and
      technical views of a complex automation system. The advantage in combining the
      two architectural frameworks lies in the simplicity of implementation and ease of
      understanding of automation system architectural elements by medical
      professionals.

PMID- 18066385
TI  - An analysis of the implementation and impact of speech-recognition technology in
      the healthcare sector.
AB  - This paper develops a conceptual framework and offers research propositions for
      understanding the adoption of speech-recognition technology, drawing from
      Rogers's work on the diffusion of innovation, from interview findings, and from
      case study analysis. The study's focus was the analysis of the implementation of
      speech recognition and its impact on performance in the healthcare industry. Our
      interview findings indicated that, while there is still much room for improvement
      in the way speech-recognition technology is adopted and implemented, this
      particular technology has had a significant impact on the ability of healthcare
      providers to operate more cost effectively and provide a better level of patient
      care.

PMID- 18066386
TI  - Database design: what HIM professionals need to know.
AB  - Database technology has been a familiar tool in the operations of most HIM
      departments and a very basic understanding of this technology has usually been
      adequate enough to allow HIM professionals to work effectively with vendors or
      information services staff. As database technology moves from the task of
      supporting paper systems to actually becoming the central digitized health
      information system, a "basic understanding" becomes inadequate. To embrace the
      digitization efforts, AHIMA has adopted an initiative called e-HIM. For e-HIM to
      be successful, it will be essential for HIM professionals entering the work force
      to have the necessary database skills to perform their jobs. The important
      question to ask is: What are those skills? This paper presents the use of a
      Nominal Group Technique to identify a group of HIM professionals who work with
      databases to identify a set of essential database skills.

PMID- 18066387
TI  - The expanding role of the HIM professional: where research and HIM roles
      intersect.
AB  - This article examines the evolving role of HIM professionals in research. In
      terms of both growth and credibility, it is important that HIM as a profession
      become more integrally involved in the research process. Specifically, this
      article examines the expanding role of the HIM professional in research-related
      activities and data management activities. For illustrative purposes, examples
      from research in the areas of medication error detection, utilization of web
      technologies in QI processes, and creation of an HIT infrastructure to connect
      healthcare providers in which HIM faculty members are actively involved in
      collaborative research projects with pharmacy, nursing, and medicine faculty in
      an academic medical center setting are provided.

PMID- 18066388
TI  - Toward a conceptual knowledge management framework in health.
AB  - This paper describes a conceptual organizing scheme for managing knowledge within
      the health setting. First, a brief review of the notions of knowledge and
      knowledge management is provided. This is followed by a detailed depiction of our
      proposed knowledge management framework, which focuses on the concepts of
      production, use, and refinement of three specific knowledge sources-policy,
      evidence, and experience. These concepts are operationalized through a set of
      knowledge management methods and tools tailored for the health setting. We
      include two case studies around knowledge translation on parent-child relations
      and virtual networks in community health research to illustrate how this
      knowledge management framework can be operationalized within specific contexts
      and the issues involved. We conclude with the lessons learned and implications.

PMID- 18066389
TI  - Critical issues in bioinformatics and computing.
AB  - This article provides an overview of the field of bioinformatics and its
      implications for the various participants. Next-generation issues facing
      developers (programmers), users (molecular biologists), and the general public
      (patients) who would benefit from the potential applications are identified. The
      goal is to create awareness and debate on the opportunities (such as career
      paths) and the challenges such as privacy that arise. A triad model of the
      participants' roles and responsibilities is presented along with the
      identification of the challenges and possible solutions.

PMID- 18066390
TI  - Redesign of diagnostic coding in pediatrics: from form-based to discharge letter
      linked.
AB  - Diagnostic coding after hospital discharge is mainly based on abstracting of
      paper medical records by medical record coders. Studies show that the quality of
      these data is often moderate, possibly because discharge registries play no role
      in daily patient care. Timely writing of discharge letters is needed to support
      continuity of care, at least in the Netherlands. This article describes the
      redesign and evaluation of diagnosis registration and discharge letter writing at
      a Dutch pediatric department.Formerly, pediatricians at this department completed
      discharge forms. However, many forms were completed with insufficient information
      or not at all. Pediatricians now provide diagnoses with codes in a special
      heading of the discharge letter. The medical record coder checks and corrects
      this diagnosis heading. A list of diagnoses for pediatrics, based on ICD-9-CM,
      was developed and alphabetically ordered into one booklet used by pediatricians
      when dictating discharge letters. A reminder system for in-time writing of
      letters was implemented. Since 1995, this discharge letter-linked registration
      has proven to be applicable in daily care. How accurately pediatricians filled in
      the diagnosis heading was analyzed during two periods. In 1995, 25 percent of the
      diagnoses were initially (before adjustments made by the medical record coder)
      not coded or incorrectly coded; nine percent of these shortcomings could be
      attributed to the pediatricians. In 1997, 67 percent of the diagnoses were
      initially not coded or incorrectly coded; 37 percent of these shortcomings were
      attributable to pediatricians. Initially, only half of the letters were written
      within six weeks after discharge. The correction function of the medical record
      coder is indispensable.

PMID- 18066391
TI  - Implementing patient access to electronic health records under HIPAA: lessons
      learned.
AB  - In 2001, the Institute of Medicine (IOM) and the Health Insurance Portability and
      Accountability Act (HIPAA) emphasized the need for patients to have greater
      control over their health information. We describe a Boston healthcare system's
      approach to providing patients access to their electronic health records (EHRs)
      via Patient Gateway, a secure, Web-based portal. Implemented in 19 clinic sites
      to date, Patient Gateway allows patients to access information from their medical
      charts via the Internet in a secure manner. Since 2002, over 19,000 patients have
      enrolled in Patient Gateway, more than 125,000 patients have logged into the
      system, and over 37,000 messages have been sent by patients to their practices.
      There have been no major security concerns. By providing access to EHR data,
      secure systems like Patient Gateway allow patients a greater role in their
      healthcare process, as envisioned by the IOM and HIPAA.

PMID- 18066392
TI  - Quantum-Mechanical QSPR Models for Polymerization Volume Change of Epoxides and
      Methacrylates Based on Mercury Dilatometry Results.
AB  - Polymerization volume change (PVC) was measured systematically using mercury
      dilatometry for 41 epoxide and methacrylate monomers with quartz filler.
      Quantitative structure property relationship (QSPR) models were developed based
      on this previously unreported data to gain insight in the data collection method
      for future models. Successful models included only data from those samples which
      polymerized to hardness. The most significant descriptors in these models related
      to monomer reactivity. In contrast, PVC data collected under experimental
      conditions which maximized monomer conversion resulted in descriptors describing
      size and branching, indicating conversion must be considered for future PVC
      measurements. A Rule of Mixtures (ROM) correction term improved correlations of
      the dilatometer data with varying quartz content, and an adjustment for
      conversion may similarly enable inclusion of data which had not polymerize to
      hardness.

PMID- 18066393
TI  - Competence to make treatment decisions in anorexia nervosa: thinking processes
      and values.
AB  - This paper explores the ethical and conceptual implications of the findings from
      an empirical study of decision-making capacity in anorexia nervosa. In the study,
      ten female patients aged 13 to 21 years with a diagnosis of anorexia nervosa, and
      eight sets of parents, took part in semi-structured interviews. The purpose of
      the interviews was to identify aspects of thinking that might be relevant to the
      issue of competence to refuse treatment. All the patient participants were also
      tested using the MacCAT-T test of competence. This is a formalised, structured
      interviewer-administered test of competence, which is a widely accepted clinical
      tool for determining capacity. The young women also completed five brief self
      administered questionnaires to assess their levels of psychopathology.The issues
      identified from the interviews are described under two headings: difficulties
      with thought processing, and changes in values. The results suggest that
      competence to refuse treatment may be compromised in people with anorexia nervosa
      in ways that are not captured by traditional legal approaches or current
      standardised tests of competence.

PMID- 18066394
TI  - Re-Assessing the Relationship between High School Sports Participation and
      Deviance: Evidence of Enduring, Bifurcated Effects.
AB  - Despite its longstanding popular appeal, the idea that athletic activity is a
      deterrent to crime and delinquency suffers from a distinct lack of empirical
      support. This paper tests the hypotheses that the relationship between high
      school sports participation and deviance varies by both type of deviant behavior
      and level of athletic involvement. The analysis is based upon longitudinal data
      focusing on the effects of involvement in high school sports, the country's
      largest institutional setting for youth sports participation, in early adulthood.
      We find that the relationship between athletic involvement and deviance varies
      significantly depending upon the deviant behaviors examined. Specifically, we
      find that shop-lifting decreases with sports participation, while drunken driving
      increases. Moreover, these effects extend further into the life course (age 30)
      than has been demonstrated in any previous study and hold across all our measures
      of sports participation. Several potential explanatory mechanisms are evaluated.
      The implications of these enduring, bifurcated effects are discussed.

PMID- 18066395
TI  - Measures of Effortful Regulation for Young Children.
AB  - Emotion-related regulation is a topic of increasing interest among researchers,
      yet there is little agreement on ways to measure emotion regulation in young
      children. In this paper, we first consider important conceptual distinctions in
      regard to the different types of emotion-related regulation and control. Next, we
      describe a number of ways researchers have assessed children's regulation. We
      also present data from the Toddler Emotional Development project, in which
      laboratory-based measures of effortful regulation were used. In this section, we
      highlight the measures that show promise (and those that did not work well).
      Future directions for research on the measurement of effortful regulation are
      presented.

PMID- 18066396
TI  - The search for polyprenols in dendroflora of Vietnam.
AB  - The occurrence of polyprenols in leaves of over 340 species of dendroflora in
      natural habitats in the regions of Hanoi and Hue in Vietnam was studied. Plant
      material was collected in the late autumn (October/November) during the end of a
      vegetation season. Leaves of about 200 plant species did not contain detectable
      amounts of polyprenols in contrast to few systematic families, e.g. Moraceae,
      Euphorbiaceae, where polyprenols were highly abundant and their pattern could be
      used as a chemotaxonomic criterion. Most often dominating polyprenols were prenol
      11 and prenol-12. In several angiosperm species prenol-13 and detectable amounts
      of prenol-14 were also found. The incidence of prenol-13 and -14 was not
      restricted to a specific taxonomic group since species exhibiting domination of
      such longer chain polyprenols belonged to various systematic families. In some
      plants (e.g. Ceiba pentandra) alpha-cis polyprenols were accompanied by alpha
      trans counterparts. This report describes several new plant species that may
      serve as natural sources of long chain polyprenols.

PMID- 18066397
TI  - New cationic polyprenyl derivative proposed as a lipofecting agent.
AB  - Cationic linear poly-cis-isoprenoid prepared from natural plant polyprenol in a
      mixture with dioleyl phosphatidylethanolamine was found to be an effective
      lipofection agent for eukaryotic cells. The transfecting activity is related to
      the poly-cis structure of the polyprenyl chain.

PMID- 18066398
TI  - Synthesis and anti-HIV properties of novel 6-phenylselenenyl-5-propyluracils.
AB  - Novel 6-phenylselenenyl-5-propyluracils were synthesized from 5-propyluracil with
      the use of regioselective synthesis to give 1-[(2-hydroxyethoxy)-methyl]-6
      phenylselenenyl-5-propyluracil (6), 1-ethoxymethyl-6-phenylselenenyl-5
      propyluracil (9) and 1-benzyloxymethyl-6-phenylselenenyl-5-propyluracil (10).
      Interaction of these compounds with recombinant HIV-1 reverse transcriptase (RT)
      was evaluated using a non-isotopic colorimetric method. Compounds 9 and 10
      exerted potent HIV RT inhibition (IC(50) 0.06 and 0.05 microM respectively) while
      compound 6 showed moderate inhibition (IC(50) = 3.5 microM). Potent anti-HIV-1
      activity in MT-2 cells inoculated by a syncythia-inducing HIV-1 (cat #3 strain)
      laboratory isolate was exerted by compounds 9 and 10 (EC(50) 0.62 microM and
      0.025 microM, respectively), while compound 6 showed only moderate activity
      (IC(50) = 4.1 microM). In addition, compound 10 showed very good in vitro
      therapeutic index (TI > 2046), indicating that it is a potential anti-HIV/AIDS
      drug.

PMID- 18066399
TI  - In vitro plant tissue cultures accumulate polyisoprenoid alcohols.
AB  - In vitro cultivated plant cells and tissues were found to synthesize
      polyisoprenoids. Taxus baccata suspension cell cultures accumulated
      polyisoprenoids of the same pattern as the parental tissue; methyl jasmonate or
      chitosan treatment almost doubled their content. All the root cultures studied
      accumulated dolichols as predominant polyisoprenoids. Roots of Ocimum sanctum
      grown in vitro accumulated approx. 2.5-fold higher amount of dolichols than the
      roots of soil-grown plants. Dolichols dominated over polyprenols in all Triticum
      sp. tissues studied.

PMID- 18066400
TI  - Changes in the content of gamma-linolenic C18:3 (n-6) and stearidonic C18:4 (n-3)
      acids in developing seeds of viper's bugloss Echium vulgare L.
AB  - Changes in the composition of fatty acids (FA) were determined in lipid extracts
      isolated from developing ovaries containing ovules and developing seeds of Echium
      vulgare L. The samples were collected successively over 20 days beginning with
      the first day after flowering. The contents of the n-6 FA family members, i.e.,
      gamma-linolenic (GLA) (C(18:3)) and linoleic (LA) (C(18:2)) acids changed in a
      parallel manner and reached the maximum of 13.9% and 24%, respectively, on the
      12th day, after which they fell systematically down to 8.6% and 18.2%,
      respectively, on the 20th day after flowering. Starting with day 13, the content
      of alpha-linolenic acid (ALA) (C(18:3) n-3) begins to grow intensively, from
      24.2% to 39.3% on the 20th day after flowering. The increase in the content of
      stearidonic acid (SDA) (C(18:4) n-3), up to 10.5% on the 20th day after
      flowering, occurred steadily as the seeds developed, and was independent of the
      changes in the content of GLA and LA. The pattern of changes in the content of
      SDA, GLA, LA and ALA during the development of seeds, and the occurrence of SDA
      in the seed oil of other plants, demonstrate that the biosynthesis of SDA in the
      seeds is critically dependent on the presence of ALA. The above condition
      indicates that SDA biosynthesis in the seeds of Echium vulgare follows the scheme
      LA --> simultaneous, competitive, action of Delta(6) and Delta(15) desaturases,
      leading to the formation of GLA and ALA, respectively, and then ALA (Delta(6)
      des) --> SDA. The biosynthesis according to the scheme: GLA (Delta(15) des) -->
      SDA is highly unlikely.

PMID- 18066401
TI  - Polyadenylation and decay of 26S rRNA as part of Nicotiana tabacum response to
      cadmium.
AB  - In contrast to mRNAs, ribosomal RNAs are generally not considered to be
      polyadenylated. Only a few recent reports describe non-abundant polyadenylated
      rRNA-related transcripts that have been detected and characterized in yeast and
      in human cells. Here we depict the phenomenon of 26S rRNA polyadenylation and
      degradation that was observed in shoots of Nicotiana tabaccum plants grown in the
      presence of cadmium. Fragments corresponding to 26S rRNA were identified using
      suppression subtractive hybridization during screening for genes induced in
      tobacco plants upon a three-week exposure to 15 microM cadmium chloride. Extracts
      prepared from the above-ground tissues of cadmium-treated tobacco plants were
      supposed to contain exclusively polyadenylated mRNAs. Surprisingly, numerous
      polyadenylated fragments matching parts of 26S rRNA were identified and their
      presence was confirmed by Northern blot and cDNA amplification techniques. To our
      knowledge this is the first report on rRNA polyadenylation in plants.

PMID- 18066402
TI  - Molecular analysis of three novel G6PD variants: G6PD Pedoplis-Ckaro, G6PD
      Piotrkow and G6PD Krakow.
AB  - We present three novel mutations in the G6PD gene and discuss the changes they
      cause in the 3-dimensional structure of the enzyme: 573C-->G substitution that
      predicts Phe to Leu at position 191 in the C-terminus of helix alphae, 851T-->C
      mutation which results in the substitution 284Val--> -->Ala in the beta+alpha
      domain close to the C-terminal part of helix alphaj, and 1175T-->C substitution
      that predicts Ile to Thr change at position 392.

PMID- 18066403
TI  - The Suzuki-Miyaura reaction in the chemical transformations of vindoline.
AB  - Vindoline and its analogues are important constituents of the Madagascan
      periwinkle Catharanthus roseus, and some of them are valuable chemotherapy drugs
      used in treatment for some types of cancer, including leukaemia, lymphoma, breast
      and lung cancer. The search for semi-synthetic congeners of natural substances is
      still an important task for organic chemistry. In this communication we report
      the synthesis of five new vindoline derivatives, 15-(2-methoxyphenyl)vindoline
      11, 15-(3-methoxyphenyl)vindoline 12, 15-(2-nitrophenyl)vindoline 13, 15-(3
      cyanophenyl)vindoline 15, and 15-(4-cyanophenyl)vindoline 16 using the Suzuki
      Miyaura reaction as the key step. X-Ray analysis of compound 16 is also reported.

PMID- 18066404
TI  - Dermatan sulfate remodeling associated with advanced Dupuytren's contracture.
AB  - Dermatan sulfate (DS) widespread as a component of extracellular matrix
      proteoglycans, is characterized by great bio-reactivity and remarkable structural
      heterogeneity due to distinct degrees of sulfation and glucuronosyl epimerization
      and different polymerization degrees. However, DS metabolism under various
      biological conditions is poorly known. Dupuytren's contracture is a benign
      fibromatosis leading to complex remodeling of the palmar fascia structure and
      properties. However, it remains unclear whether the disease affects the structure
      of DS, which is the major tissue glycosaminoglycan. Thus the aim of the study was
      to examine the structure of the total DS in Dupuytren's fascia. DS chains were
      extracted from 5 samples of normal fascia and 7 specimens of Dupuytren's tissue
      by papain digestion followed by fractionation with cetylpyridinium chloride.
      Then, DS structure analysis was performed comprising the evaluation of its
      molecular masses and sensitivity to hyaluronidase and chondroitinase B.
      Dupuytren's contracture is associated with significant remodeling of DS chain
      structure revealed by (1) a distinct profile of chain molecular masses
      characterized by the appearance of long size components as well as the increase
      in the content of small size chains; (2) a different glucuronosyl epimerization
      pattern connected with the enhanced content of glucuronate disaccharide blocks;
      (3) chain oversulfation. These structural alterations in total DS may modify the
      GAG interactions especially affecting collagen fibrillogenesis and growth factor
      availability. Thus, Dupuytren's contracture associated DS remodeling may promote
      the phenomena typical for advanced disease: apoptosis and reduction in cell
      number as well as the appearance of dense pseudotendinous collagen matrix.

PMID- 18066405
TI  - Limitation of usage of PicoGreen dye in quantitative assays of double-stranded
      DNA in the presence of intercalating compounds.
AB  - PicoGreen is a very sensitive fluorescent dye for quantitative assays of double
      stranded DNA (dsDNA) in solution and is used in several analytical protocols in
      which sensitive and precise DNA detection is needed, also for examination of drug
      DNA interactions. The data shown in this paper indicate that compounds
      intercalating to DNA influence the applicability of PicoGreen dye for
      quantitative measurements of dsDNA, and for this reason PicoGreen dye is not
      suitable for examination of drug-DNA interactions, especially interstrand DNA
      crosslinks.

PMID- 18066406
TI  - Distinct role of clathrin-mediated endocytosis in the functional uptake of
      cholera toxin.
AB  - The involvement of the clathrin-mediated endocytic internalization route in the
      uptake of cholera toxin (CT) was investigated using different cell lines,
      including the human intestinal Caco-2 and T84 cell lines, green monkey Vero
      cells, SH-SY5Y neuroblastoma cells and Madin-Darby canine kidney cells.
      Suppression of the clathrin-mediated endocytic pathway by classical biochemical
      procedures, like intracellular acidification and potassium depletion, inhibited
      cholera toxin uptake by up to about 50% as well as its ability to raise
      intracellular levels of cAMP. Also prior exposure of these cell types to the
      cationic amphiphilic drug chlorpromazine reduced the functional uptake of cholera
      toxin, even to a greater extent. These effects were dose- and cell type
      dependent, suggesting an involvement of clathrin-mediated endocytosis in the
      functional uptake of cholera toxin. For a more straightforward approach to study
      the role of the clathrin-mediated uptake in the internalization of cholera toxin,
      a Caco-2(eps-) cell line was exploited. These Caco-2(eps-) cells constitutively
      suppress the expression of epsin, an essential accessory protein of clathrin
      mediated endocytosis, thereby selectively blocking this internalization route. CT
      uptake was found to be reduced by over 60% in Caco-2(eps-) paralleled by a
      diminished ability of CT to raise the level of cAMP. The data presented suggest
      that the clathrin-mediated uptake route fulfils an important role in the
      functional internalization of cholera toxin in several cell types.

PMID- 18066407
TI  - Formation of lipid droplets induced by 2,3-dihydrogeranylgeranoic acid distinct
      from geranylgeranoic acid.
AB  - Geranylgeranoic acid (GGA) and 2,3-dihydrogeranylgeranoic acid (2,3-diGGA) are
      geranylgeraniol-derived metabolites (Kodaira et al. (2002) J Biochem 132: 327
      334). In the present study, we examined the effects of these acids on HL-60
      cells. The cells were differentiated into neutrophils by GGA stimulation like
      retinoic acid stimulation. In the case of cells stimulated with 2,3-diGGA,
      neutrophils were not detected, but the formation of lipid droplets was induced.
      On the other hand, when the cells were cultured in the presence of 0.1% FBS
      instead of 10% FBS, apoptotic cells were induced not only by GGA stimulation but
      also with 2,3-diGGA. In the latter case, when the cells were cultured in the co
      presence of a caspase-3 inhibitor (Ac-DMQD-CHO), the lipid droplets formation was
      observed in the cells. These results suggest that GGA and 2,3-diGGA are extremely
      different from each other with respect to their effects on HL-60 cells.

PMID- 18066408
TI  - Analysis of gypsogenin saponins in homeopathic tinctures.
AB  - A relatively simple and short procedure for the quantitative determination of
      gypsogenin saponins was performed to evaluate homeopathic tinctures in which
      those compounds can be regarded as one of the active constituents. This method
      comprises partial hydrolysis of saponins, subsequent extraction of liberated
      prosaponin (gypsogenin 3-O-glucuronide) and its analysis by high performance
      liquid chromatography. Glycyrrhizic acid was used as an internal standard. This
      method was successfully applied to the analysis of mother tinctures obtained from
      Saponaria officinalis. Thus, the determination of triterpenoid saponins can be
      used as a convenient and sufficient method of standardization of selected
      homeopathic tinctures.

PMID- 18066409
TI  - The Student Editorial Board of Methods of Information in Medicine--an opportunity
      to educate tomorrow's peer reviewers.
AB  - OBJECTIVE: Peer review is a critical process in the publication of scientific
      findings; trainees and young investigators, however, have few opportunities to
      learn systematically how to review manuscripts. Journal editors have an
      opportunity to engage trainees and young investigators in the peer review process
      early during their career. METHODS: Methods of Information in Medicine, an
      official journal of the International Medical Informatics Association, is
      initiating a Student Editorial Board. The journal invites applications from
      international graduate and post-doctoral training programs that have a focus on
      health informatics, biomedical informatics, or a related field. RESULTS: Each
      year up to six trainees will be invited to join the Student Editorial Board. The
      trainees will go through a mentored training experience that includes an active
      involvement in the various aspects of peer review during their one to two-year
      term of appointment. CONCLUSIONS: The journal expects that the Student Editorial
      Board will benefit trainees and young investigators in becoming skilled reviewers
      and engaged peers who can offer professional, constructive, and informative
      feedback and enhance the process of scientific communication.

PMID- 18066410
TI  - Let a thousand flowers bloom: transition towards implementation of the IMIA
      strategic plan.
AB  - OBJECTIVE: IMIA, the International Medical Informatics Association, has adopted
      the IMIA Strategic Plan, "Towards IMIA 2015". In order to turn the vision into
      reality, we invite all members of IMIA, and others with an interest in our work,
      to engage in activities designed to achieve the key strategic goals of the plan.
      METHODS: IMIA members and others are invited to study the IMIA Strategic Plan,
      and consider developing, or contributing to, proposals that can support the
      implementation of one or more parts of the Strategic Plan. IMIA has allocated a
      proportion of reserve funds for projects supporting the implementation of the
      plan, and proposals can be submitted to the Interim Vice President for Strategic
      Planning Implementation. RESULTS AND CONCLUSIONS: Several projects are already
      being undertaken to support implementation of the IMIA Strategic Plan. IMIA looks
      forward to its members undertaking further projects, targeted at achieving its
      strategic goals and making the vision a reality by 2015.

PMID- 18066411
TI  - Requirements analysis of information services for patients on a general
      practitioner's website--patient and general practitioner's perspectives.
AB  - OBJECTIVE: To elicit and analyze information needs of patients and primary care
      physicians (GPs) regarding the information services (static and functional) that
      a GP's practice website should provide. METHODS: To find candidate information
      services, we conducted a literature search and examined primary care physicians'
      websites, especially Dutch websites. Semi-structured depth interviews with the
      stakeholders, Dutch patients and GPs, were done to arrive at a final checklist.
      We then conducted a survey to elicit the level of importance associated with each
      service on the checklist. The data underwent statistical analysis and relevant
      requirements were formulated. The requirements were then validated by interviews.
      General website quality and usability aspects were elicited from the literature.
      RESULTS: The research resulted in a checklist of 38 selected information services
      including their priority ratings for patients and GPs; a discrepancy list between
      GP and patient priorities; and a requirements document containing information
      services (14 static and 6 functional), and general quality and usability aspects
      (8 and 5). CONCLUSION: The following items occurred in the top 10 of both user
      groups: general practice information, information of local public health
      institutions, self-help information, repeat prescription, links to health web
      sites. At the bottom on both priority lists were: links to journals, tests and
      forums. Dutch GPs are much more selective in terms of which information services
      to provide on-line. Discrepancy between the two groups concerns on-line services
      that seem to require a change to the GP's workflow, or those services that are
      not recognized for reimbursing the GP. Although the Dutch patients' requirements
      seem to generalize to other patients, the conflict list might depend on the
      primary care system.

PMID- 18066412
TI  - Supporting medical planning by mitigating cognitive load.
AB  - OBJECTIVES: Developing a care plan for a patient is a complex task, requiring an
      understanding of interactions and dependencies between procedures and of their
      possible outcomes for an individual patient. Decision support for planning has
      broader requirements than are typically considered in medical informatics
      applications. We consider the appropriate design of software to assist medical
      planning. METHODS: The likely cognitive loads imposed by planning tasks were
      assessed with a view to directly supporting these via software. RESULTS: Five
      types of cognitive load are likely to be important. A planning support system,
      REACT, was designed to ameliorate these cognitive loads by providing targeted
      dynamic feedback during planning. An initial evaluation study in genetic
      counselling indicates that the approach is successful in that role. CONCLUSIONS:
      The approach provides the basis of a general aid for visualizing, customizing and
      evaluating care plans.

PMID- 18066413
TI  - Implementing software development guidelines in a medical informatics research
      project.
AB  - OBJECTIVES: Due to the non-commercial, research-oriented context, software in
      medical informatics research projects is often developed by researchers as a
      proof-of-concept without applying structured software development process models.
      A guideline for software development can bring sufficient structure to the
      development process while avoiding the complexity of industry-standard methods.
      METHODS: We adapted the common evidence-based guideline development process from
      medicine to build a guideline for software development in our medical informatics
      teaching and research project. RESULTS: Our guideline development used the six
      steps of problem identification, first proposal, review, revision, gaining
      consensus and periodic guideline review. Since the developers had taken part in
      guideline development, our guideline clearly states the consensus of the
      development team over critical topics. The guideline improved the quality of our
      source code in structure and understandability. CONCLUSIONS: A software
      development guideline that is developed following a consensus panel approach is a
      good instrument for basic software quality assurance in domains where complex,
      industry-standard software development methods cannot be applied. This is
      especially the case in non-commercial, research-oriented medical informatics
      projects where mainly non-software engineers like students do the development
      work.

PMID- 18066414
TI  - Detection of phase singularities in triangular meshes.
AB  - OBJECTIVES: Phase singularities have become a key marker in animal and computer
      models of atrial and ventricular fibrillation. However, existing algorithms for
      the automatic detection of phase singularities are limited to regular, quadratic
      mesh grids. We present an algorithm to automatically and exactly detect phase
      singularities in triangular meshes. METHODS: For each node an oriented path
      inscribing the node with one unit of spatial discretization is identified. At
      each time step the phase information is calculated for all nodes. The so-called
      topological charge is also computed for each node. A non-zero (+/- 2pi) charge is
      obtained for all nodes with a path enclosing a phase singularity. Thus all
      charged nodes belonging to the same phase singularity have to be clustered.
      RESULTS: With the use of the developed algorithm, phase singularities can be
      detected in triangular meshes with an accuracy of below 0.2 mm - independent of
      the type of membrane kinetics used. CONCLUSIONS: With the possibility to detect
      phase singularities automatically and exactly, important quantitative data on
      cardiac fibrillation can be gained.

PMID- 18066415
TI  - Proposals for sample size calculation programs.
AB  - OBJECTIVES: Numerous sample size calculation programs are available nowadays.
      They include both commercial products as well as public domain and open source
      applications. We propose modifications for these programs in order to even better
      support statistical consultation during the planning stage of a two-armed
      clinical trial. METHODS: Directional two-sided tests are commonly used for two
      armed clinical trials. This may lead to a non-negligible Type III error risk in a
      severely underpowered study. In the case of a reasonably sized study the question
      for the so-called auxiliary alternative may evolve. RESULTS: We propose that
      sample size calculation programs should be able to compute i) Type III errors and
      the so-called q-values, ii) minimum sample sizes required to keep the q-values
      below pre-specified levels, and iii) detectable effect sizes of the so-called
      auxiliary alternatives. CONCLUSIONS: Proposals i and ii are intended to help
      prevent irresponsibly underpowered clinical trials, whereas the proposal iii is
      meant as additional assistance for the planning of reasonably sized clinical
      trials.

PMID- 18066416
TI  - An exact test for meta-analysis with binary endpoints.
AB  - OBJECTIVES: We reintroduce an exact Mantel-Haenszel (MH) procedure for meta
      analysis with binary endpoints which is expected to work especially well in
      sparse data, e.g., in meta-analyses of safety or adverse events. METHODS: The
      performance of the exact MH procedure in terms of empirical size and power is
      compared to the asymptotic MH and to the two standard procedures (fixed effects
      and random effects model) in a simulation study. We illustrate the methods with a
      meta-analysis of postoperative stroke occurrence after off-pump or on-pump
      surgery in coronary artery bypass grafting. RESULTS: We find that in almost all
      situations the asymptotic MH procedure outperforms its competitors; especially
      the standard methods yield poor results in terms of power and size. CONCLUSIONS:
      There is no need to use the reintroduced exact MH procedure; the asymptotic MH
      procedure will be sufficient in most practical situations. The standard methods
      (fixed effects and random effects model) should not be used in the sparse data
      situation.

PMID- 18066418
TI  - UMIN online abstract and paper entry system for biomedical academic meetings--an
      overview and its impact on the distribution of digitalized academic information
      in Japan.
AB  - OBJECTIVES: The object of this research is to develop and evaluate the Online
      Abstract and Paper Entry System (OAPES) that collects and delivers medical
      academic meeting information online in Japan. METHODS: CGI technology and semi
      automated program generation method are employed for the OAPES software
      development to accommodate the various data collected by many meetings in a
      common data format and to achieve both flexibility and efficiency. RESULTS: Using
      OAPES, an abstract, or paper, and its related information can be submitted via
      the Internet. After contributions have been accepted, bibliographic information
      is automatically added to the bibliographic information database that is
      retrievable, free of charge, from the Internet. Since 1997, we have provided
      OAPES for biomedical academic meetings in Japan. In fiscal 2006, 488 biomedical
      academic meetings, most of those held in Japan, used OAPES; 106,461 abstracts and
      papers were handled. To the best of our knowledge, there are no other abstract
      entry systems in any populous country that are almost monopolistic in a
      particular major academic field in the way OAPES is. The data format of OAPES and
      its user interface are now the de facto standard for academic information
      exchange related to academic meetings in Japan. CONCLUSIONS: We succeeded in
      developing an efficient and prompt online collection and delivery system for
      medical academic meeting information in Japan and demonstrated that it really
      works.

PMID- 18066419
TI  - Development of hospital data warehouse for cost analysis of DPC based on medical
      costs.
AB  - OBJECTIVES: To develop a data warehouse system for cost analysis, based on the
      categories of the diagnosis procedure combination (DPC) system, in which medical
      costs were estimated by DPC category and factors influencing the balance between
      costs and fees. METHODS: We developed a data warehouse system for cost analysis
      using data from the hospital central data warehouse system. The balance data of
      patients who were discharged from Kagoshima University Hospital from April 2003
      to March 2005 were determined in terms of medical procedure, cost per day and
      patient admission in order to conduct a drill-down analysis. To evaluate this
      system, we analyzed cash flow by DPC category of patients who were categorized as
      having malignant tumors and whose DPC category was reevaluated in 2004. RESULTS:
      The percentages of medical expenses were highest in patients with acute leukemia,
      non-Hodgkin's lymphoma, and particularly in patients with malignant tumors of the
      liver and intrahepatic bile duct. Imaging tests degraded the percentages of
      medical expenses in Kagoshima University Hospital. CONCLUSIONS: These results
      suggested that cost analysis by patient is important for hospital administration
      in the inclusive evaluation system using a case-mix index such as DPC.

PMID- 18066420
TI  - Risk management and measuring productivity with POAS--Point of Act System--a
      medical information system as ERP (Enterprise Resource Planning) for hospital
      management.
AB  - OBJECTIVES: The concept of our system is not only to manage material flows, but
      also to provide an integrated management resource, a means of correcting errors
      in medical treatment, and applications to EBM (evidence-based medicine) through
      the data mining of medical records. METHODS: Prior to the development of this
      system, electronic processing systems in hospitals did a poor job of accurately
      grasping medical practice and medical material flows. With POAS (Point of Act
      System), hospital managers can solve the so-called, "man, money, material, and
      information" issues inherent in the costs of healthcare. RESULTS: The POAS system
      synchronizes with each department system, from finance and accounting, to
      pharmacy, to imaging, and allows information exchange. We can manage Man
      (Business Process), Material (Medical Materials and Medicine), Money (Expenditure
      for purchase and Receipt), and Information (Medical Records) completely by this
      system. CONCLUSIONS: Our analysis has shown that this system has a remarkable
      investment effect - saving over four million dollars per year - through cost
      savings in logistics and business process efficiencies. In addition, the quality
      of care has been improved dramatically while error rates have been reduced -
      nearly to zero in some cases.

PMID- 18066421
TI  - A pen-based interface for generating graphical reports of findings in cardiac
      catheterization.
AB  - OBJECTIVES: This paper introduces a pen-based interface for the graphical
      reporting of findings in cardiac catheterization. METHODS: The user can
      interactively draw, erase, move, and deform coronary arteries as well as record
      stenoses on them. The location and degree of each stenosis is represented
      visually and the doctor can record various treatments such as bypasses and stents
      on the diagram. In addition, the system automatically extracts semantic
      information from the graphical representation and stores it in XML format. The
      system can also generate a table in the format specified by the American Heart
      Association. RESULTS: Our current implementation is a research prototype and is
      not yet being used in clinical practice. However, we have already demonstrated it
      to medical professionals and confirmed the following benefits. CONCLUSIONS: This
      system is useful not only as a tool for efficiently generating reports of
      findings but also as an effective explanation tool for patients.

PMID- 18066422
TI  - Document recognition and XML generation of tabular form discharge summaries for
      analogous case search system.
AB  - OBJECTIVES: This paper discusses and develops a document image recognition,
      keyword extraction and automatic XML generation system to search analogous cases
      from paper-based documents. In this paper, we propose the document structure
      recognition method and automatic XML generation method for the tabular form
      discharge summary documents. This paper also develops the prototype system using
      the proposed method. Evaluation experiments using actual documents are done to
      discuss the effectiveness of the developed system. METHODS: The developed system
      consists of the following methods. Paper-based summary documents are scanned by a
      scanner using 300 dpi first. Noise and tilt of the image are reduced by pre
      processing, and the table structures are identified. Characters in the table are
      recognized and converted to text data by the OCR engine. XML documents are
      automatically generated using obtained results. RESULTS: In this paper, patient
      discharge summary documents archived at Mie University Hospital were used. The
      results show that XML documents can be automatically generated when standard
      tabular form documents are input into the developed system. In this experiment,
      it takes about 20 seconds to generate an XML document using the general personal
      computer. This paper also compares the developed system with a commercial product
      to discuss the effectiveness of the present system. Experimental results also
      show that the accuracy of table structure recognition is high and it can be used
      in a practical situation. CONCLUSIONS: This paper showed the effectiveness of the
      proposed method to recognize the tabular form document images to generate XML
      documents.

PMID- 18066423
TI  - Development of a broadband telemedical network based on internet protocol in the
      Asia-Pacific region.
AB  - OBJECTIVES: To promote the exchange of knowledge and standardization of medical
      procedures and medical systems in the Asia-Pacific region, we established a
      medical network with high-quality moving images over broadband Internet lines in
      February 2003. METHODS: Real-time teleconferences and live demonstrations with
      medical-quality videos, broadcast via the Digital Video Transport System, have
      been used to teach surgical techniques and other medical procedures across
      national borders. The Asia-Pacific Advanced Network (APAN) committee in August
      2005 formally approved our proposal to establish a medical working group within
      APAN. The network was expanded by the launch of the Trans-Eurasia Information
      Network 2 in 2006. By the end of 2006, we had conducted 82 events, in 10
      countries in the Asia-Pacific region. The multi-station event has increased every
      year. RESULTS: There have been no serious transmission problems or ethical
      conflicts so far. With these experiences and current achievements, we hope to
      extend this advanced network system to the entire Asia-Pacific. CONCLUSION: This
      system is a promising and very useful tool for the standardization of medical
      system and procedures across national borders. Drawing upon these experiences and
      current achievements, we hope to extend this advanced network system to the
      entire Asia-Pacific region.

PMID- 18066424
TI  - An improved computer-aided diagnosis scheme using the nearest neighbor criterion
      for determining histological classification of clustered microcalcifications.
AB  - OBJECTIVES: Our purpose was to evaluate the potential usefulness of the nearest
      neighbor case which was assumed to be the similar case in a CAD scheme for
      determining the histological classification of clustered microcalcifications.
      METHODS: Our database consisted of current and previous magnification mammograms
      obtained from 93 patients before and after three-month follow-up examination. It
      included 11 invasive carcinomas, 19 noninvasive carcinomas of the comedo type, 25
      non-invasive carcinomas of the noncomedo type, 23 mastopathies, and 15
      fibroadenomas. Six objective features on clustered microcalcifications were first
      extracted from each of the current and the previous images. The nearest neighbor
      case was then identified by the Euclidean distance in the previous and current
      feature-space. The histological classification of an unknown new case in question
      was assumed to be the same as that of the nearest neighbor case which has the
      shortest Euclidean distance in our database. RESULTS: The classification
      accuracies were 90.9% for invasive carcinoma, 89.5% for noninvasive carcinoma of
      the comedo type, 96.0% for noninvasive carcinoma of the noncomedo type, 82.6% for
      mastopathy, and 93.3% for fibroadenoma. These results were substantially higher
      than those with our previous CAD scheme. CONCLUSION: The nearest neighbor
      criterion was useful in a CAD scheme for determining the histological
      classification.

PMID- 18066425
TI  - Accuracy in the diagnostic prediction of acute appendicitis based on the Bayesian
      network model.
AB  - OBJECTIVES: The diagnosis of acute appendicitis is difficult, and a diagnostic
      error will often lead to either a perforation or the removal of a normal
      appendix. In this study, we constructed a Bayesian network model for the
      diagnosis of acute appendicitis and compared the diagnostic accuracy with other
      diagnostic models, such as the naive Bayes model, an artificial neural network
      model, and a logistic regression model. METHODS: The data from 169 patients, who
      suffered from acute abdominal pain and who were suspected of having an acute
      appendicitis, were analyzed in this study. Nine variables were used for the
      evaluation of the accuracy of the four models for the diagnosis of an acute
      appendicitis. The naive Bayes model, the Bayesian network model, an artificial
      neural network model, and a logistic regression model were used in this study for
      the diagnosis of acute appendicitis. These four models were validated by using
      the ".632+ bootstrap method" for resampling. The levels of accuracy of the four
      models for diagnosis were compared by the error rates and by the areas under the
      receiver operating characteristic curves. RESULTS: Through the course of illness,
      50.9% (86 of 169) of the patients were diagnosed as having an acute appendicitis.
      The error rate was the lowest in the Bayesian network model, as compared with the
      other diagnostic models. The area under the receiver operating characteristic
      curve analysis also showed that the Bayesian network model provided the most
      reliable results. CONCLUSION: The Bayesian network model provided the most
      accurate results in comparison to other models for the diagnosis of acute
      appendicitis.

PMID- 18066426
TI  - Artifact and head movement compensation in MEG.
AB  - PURPOSE: Magnetoencephalography (MEG) is traditionally considered impractical if
      the subject's head moves during measurements. A novel approach to correct the
      head position and the associated movement-related artifacts does, however, exist:
      continuous head position monitoring and movement compensation (MC) realized by
      the signal space separation (SSS) or its temporal extension (tSSS). The latter is
      especially important for rejection of close-to-sensor artifacts. The goal of the
      present work was to study how MC-SSS and its temporal extension MC-tSSS would
      influence MEG results. METHODS: Somatosensory evoked MEG responses to electrical
      median nerve stimulation were recorded with 204 planar gradiometers and 102
      magnetometers. We compared the localization error of the N20m source, the
      averaged baseline noise, goodness of fit and confidence volume on data processed
      by MC-SSS vs. MC-tSSS on a subject moving in a controlled manner. RESULTS: We
      defined two patterns of disturbances with MC-SSS: stimulus artifact increase and
      random noise increase mainly on the lowermost sensors in very low head positions
      (5-6 cm shift). Up to 5-cm head shift, MC-SSS decreased mean localization error
      from 3.91 to 2.13 cm, but at the same time increased noise on gradiometers from
      3.4 to 5.3 fT/cm. The noise increment occurred simultaneously with signal
      enhancement as MC transformed the head position closer to the sensors.
      Replacement of SSS by tSSS reduced the noise on gradiometers from 5.3 to 2.8
      fT/cm and on magnetometers from 1.4 to 0.8 fT, reduced the mean localization
      error from 2.13 to 0.89 cm and increased the goodness of fit from 61.5% to 76.5%.
      Thus, tSSS specifically suppressed the random noise and nearby artifacts without
      suppressing the signal and thereby improved the signal to noise ratio.
      CONCLUSIONS: Head position recalculation should be combined with a powerful
      artifact rejection method. We recommend limiting MC use up to 3 cm head shift and
      using tSSS-based MC.

PMID- 18066427
TI  - Posterior antebrachial cutaneous nerve conduction study technique.
AB  - PURPOSE: This paper describes an improved electrodiagnostic methodology for
      posterior antebrachial cutaneous nerve (PABC) neuropathy based on retrospective
      analysis. METHODS: Results of PABC nerve conduction studies in 14 control
      patients and 3 patients with left PABC neuropathy are included. Stimulation was
      performed 0.5 to 2.0 cm above the lateral epicondyle, and the recordings were
      acquired at 12 cm, 15 cm and 20 cm distally. Data was evaluated using the mean
      A+/- standard deviation, calculated for descriptive analysis of continuous
      variables whereas frequencies and percentages were determined for categorical
      variables. Abnormal cutoff values including side-side comparison values were
      established so that all normal control values would fall within the normal range.
      RESULTS: PABC conduction studies with 20 cm recording distance demonstrated
      abnormal electrodiagnostic findings in all 3 patients, while more proximal
      recordings failed to document the neuropathy. CONCLUSION: The recording of PABC
      responses at 12 cm, 15 cm and 20 cm distal to the stimulating electrode offers a
      more comprehensive evaluation and may be a more sensitive test for evaluation of
      suspected PABC neuropathy, in comparison to traditional 12 cm recording.

PMID- 18066429
TI  - Antifungal activity of the extracts and saponins from Sapindus saponaria L.
AB  - Extracts from the dried pericarp of Sapindus saponaria L. (Sapindaceae) fruits
      were investigated for their antifungal activity against clinical isolates of
      yeasts Candida albicans and C. non-albicans from vaginal secretions of women with
      Vulvovaginal Candidiasis. Four clinical isolates of C. albicans, a single
      clinical isolated of each of the species C. parapsilosis, C. glabrata, C.
      tropicalis, and the strain of C. albicans ATCC 90028 were used. The
      hydroalcoholic extract was bioactivity-directed against a clinical isolate of C.
      parapsilosis, and showed strong activity. The n-BuOH extract and one fraction
      showed strong activity against all isolates tested. Further column-chromatography
      on silica gel separation of this fraction afforded two pure triterpene acetylated
      saponins: 3-O-(4-acetyl-beta-D-xylopyranosyl)-(1->3)-alpha-L-rhamnopyranosyl-(1
      >2)-alpha-L-arabinopyranosyl-hederagenin (1) and 3-O-(3,4-di-acetyl-beta-D
      xylopyranosyl)-(1->3)-alpha-L-rhamnopyranosyl-(1->2)-alpha-L-arabynopyranosyl
      hederagenin (2). The structures of the compounds were based on spectral data
      ((1)H and 13C NMR, HSQC, HMBC and MS), and on with literature. The saponins
      isolated showed strong activity against C. parapsilosis.

PMID- 18066430
TI  - Production of transgenic goat (Capra hircus) with human Granulocyte Colony
      Stimulating Factor (hG-CSF) gene in Brazil.
AB  - In order to produce transgenic goats with hG-CSF, a total of 24 adult Saanen and
      48 adult undefined breed goats were used as donors and recipients, respectively.
      Donors were estrus-synchronized with vaginal sponges and superovulated by a
      treatment with 200 mg FSH given twice daily in decreasing doses over 3 days
      starting 48 h before sponge removal. Ovulation was induced by injecting 100
      microg GnRH 36 h after sponge removal. The recipients also received an estrus
      synchronization treatment. Donors were mated with fertile Saanen bucks and,
      approximately 72 h after sponge removal, zygotes were recovered surgically by
      flushing oviducts. The recovered zygotes were briefly centrifuged to a reliable
      visualization of the pronuclei. The DNA construct containing hG-CSF gene flanked
      by goat and bovine alphas1-casein sequences was injected into pronuclei of 129
      zygotes. The microinjected embryos (3-6 per female) were transferred to 27
      recipients. Ten recipients became pregnant and 12 kids were born. One transgenic
      male founder was identified in the group of kids. This is the first report of a
      birth of a transgenic goat in Latin America.

PMID- 18066431
TI  - Chemical carcinogenesis.
AB  - The use of chemical compounds benefits society in a number of ways. Pesticides,
      for instance, enable foodstuffs to be produced in sufficient quantities to
      satisfy the needs of millions of people, a condition that has led to an increase
      in levels of life expectancy. Yet, at times, these benefits are offset by certain
      disadvantages, notably the toxic side effects of the chemical compounds used.
      Exposure to these compounds can have varying effects, ranging from instant death
      to a gradual process of chemical carcinogenesis. There are three stages involved
      in chemical carcinogenesis. These are defined as initiation, promotion and
      progression. Each of these stages is characterised by morphological and
      biochemical modifications and result from genetic and/or epigenetic alterations.
      These genetic modifications include: mutations in genes that control cell
      proliferation, cell death and DNA repair--i.e. mutations in proto-oncogenes and
      tumour suppressing genes. The epigenetic factors, also considered as being non
      genetic in character, can also contribute to carcinogenesis via epigenetic
      mechanisms which silence gene expression. The control of responses to
      carcinogenesis through the application of several chemical, biochemical and
      biological techniques facilitates the identification of those basic mechanisms
      involved in neoplasic development. Experimental assays with laboratory animals,
      epidemiological studies and quick tests enable the identification of carcinogenic
      compounds, the dissection of many aspects of carcinogenesis, and the
      establishment of effective strategies to prevent the cancer which results from
      exposure to chemicals.

PMID- 18066432
TI  - Microcirculation in obesity: an unexplored domain.
AB  - Obesity is traditionally linked to diabetes and cardiovascular diseases. Very
      recent experimental, clinical and epidemiological, sometimes provocative, data
      challenge this automaticity by showing that not the amount but the distribution
      of fat is the important determinant. Moderate abdominal fat accumulation may thus
      be more harmful than even consequent overweight. In view of the worldwide burden
      of obesity, factors leading to it in children and young adults must urgently be
      identified. Since obesity is a very complex cardiometabolic situation, this will
      require to focus investigations on uncomplicated obese subjects and adequate
      animal models. The recent discovery of intergenerational transmissions of obesity
      risk factors and also the key role played by gestational and perinatal events
      (epigenetic factors) give rise to completely new concepts and research avenues.
      Considering the potential close relationship between microcirculation and tissue
      metabolism, demonstrations of structural and/or functional abnormalities in
      microvascular physiology very early in life of subjects at risk for obesity might
      provide a solid basis for further investigations of such links.
      Microcirculation(arterioles, capillaries and venules) is conceivably a key
      compartment determining over one or several decades the translation of genetic
      and epigenetic factors into fat accumulation. Available animal models should
      serve to answer this cardinal question.

PMID- 18066433
TI  - Time course of echocardiographic and electrocardiographic parameters in
      myocardial infarct in rats.
AB  - In animal models the evaluation of myocardial infarct size in vivo and its
      relation to the actual lesion found post mortem is still a challenge. The purpose
      of the current study was to address if the conventional electrocardiogram (ECG)
      and/or echocardiogram (ECHO) could be used to adequately predict the size of the
      infarct in rats. Wistar rats were infarcted by left coronary ligation and then
      ECG, ECHO and histopathology were performed at 1, 7 and 28 days after surgery.
      Correlation between infarct size by histology and Q wave amplitude in lead L1 was
      only found when ECGs were performed one day post-surgery. Left ventricular
      diastolic and systolic dimensions correlated with infarct size by ECHO on day 7
      post-infarction. On days 7 and 28 post-infarction, ejection indexes estimated by
      M-mode also correlated with infarct size. In summary we show that conventional
      ECG and ECHO methods can be used to estimate infarct size in rats. Our data
      suggest that the 7-day interval is actually the most accurate for estimation of
      infarct size by ECHO.

PMID- 18066434
TI  - The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the
      chemotherapy of Chagas disease.
AB  - Trypanosoma cruzi is highly sensitive to oxidative stress caused by reactive
      oxygen species. Trypanothione, the parasite's major protection against oxidative
      stress, is kept reduced by trypanothione reductase, using NADPH; the major source
      of the reduced coenzyme seems to be the pentose phosphate pathway. Its seven
      enzymes are present in the four major stages in the parasite's biological cycle;
      we have cloned and expressed them in Escherichia coli as active proteins. Glucose
      6-phosphate dehydrogenase, which controls glucose flux through the pathway by its
      response to the NADP/NADPH ratio, is encoded by a number of genes per haploid
      genome, and is induced up to 46-fold by hydrogen peroxide in metacyclic
      trypomastigotes. The genes encoding 6-phosphogluconolactonase, 6-phosphogluconate
      dehydrogenase, transaldolase and transketolase are present in the CL Brener clone
      as a single copy per haploid genome. 6-phosphogluconate dehydrogenase is very
      unstable, but was stabilized introducing two salt bridges by site-directed
      mutagenesis. Ribose-5-phosphate isomerase belongs to Type B; genes encoding Type
      A enzymes, present in mammals, are absent. Ribulose-5-phosphate epimerase is
      encoded by two genes. The enzymes of the pathway have a major cytosolic
      component, although several of them have a secondary glycosomal localization, and
      also minor localizations in other organelles.

PMID- 18066436
TI  - Spectral characterization of mangrove leaves in the Brazilian Amazonian Coast:
      Turiacu Bay, Maranhao State.
AB  - Mangrove communities are tropical systems which have fewer species than tropical
      forests, especially in Latin America and display a single architecture, usually
      lacking the various strata commonly found in other forest ecosystems. The
      identification of mangrove communities by orbital data is not a difficult task
      but the most interesting challenge is to identify themselves by the dominant
      species. The first step toward that floristic identification is the spectral
      characterization of detached leaves. Leaves from four species of mangrove trees
      were spectrally characterized considering the Directional Hemispherical
      Reflectance Factor (DHRF) determined through radiometric measurements using an
      integrating sphere LICOR 1800 attached to a spectroradiometer SPECTRON SE-590. In
      the visible bands (0.45-0.69 microm) the button-shaped mangrove Conocarpus
      erectus was brighter and the red mangrove Rhizophora mangle was darker than the
      other two species which shows very close DHRF values. Otherwise the black
      mangrove Avicennia germinans and the white mangrove Laguncularia racemosa can be
      distinguished from one another in the Near Infra Red (NIR) region (0.76-0.90
      microm and in this region of the spectrum the DHRF of C. erectus and R. mangle
      become very close.

PMID- 18066440
TI  - The contribution of heavy metal pollution derived from highway runoff to
      Guanabara Bay sediments--Rio de Janeiro/Brazil.
AB  - In this study, geochemical and particle size analyses of thirty-four street
      sediment samples collected from an urban environment around Guanabara Bay, shows
      highway run-off to be a potential source of heavy metals for the pollution of
      near-shore sedimentary deposits. Concentrations of Fe, Mn, Zn, Cu, Pb, Cr and Ni
      were found to be higher in these sediments when compared to concentrations found
      in samples from the natural environment, where an Enrichment Factor (EF) index
      was used to distinguish between natural and anthropogenic sources. Particle size
      analysis shows these sediments to be predominantly composed of sand and no
      distribution pattern was observed between the sand, silt and clay fractions. High
      levels of organic matter and heavy metals would indicate that these street run
      off materials are a potential source of pollution for the near-shore sediments of
      Guanabara Bay.

PMID- 18066442
TI  - The 15N isotope to evaluate fertilizer nitrogen absorption efficiency by the
      coffee plant.
AB  - The use of the 15N label for agronomic research involving nitrogen (N) cycling
      and the fate of fertilizer-N is well established, however, in the case of long
      term experimentation with perennial crops like citrus, coffee and rubber tree,
      there are still shortcomings mainly due to large plant size, sampling procedures,
      detection levels and interferences on the system. This report tries to contribute
      methodologically to the design and development of 15N labeled fertilizer
      experiments, using as an example a coffee crop fertilized with 15N labeled
      ammonium sulfate, which was followed for two years. The N of the plant derived
      from the fertilizer was studied in the different parts of the coffee plant in
      order to evaluate its distribution within the plant and the agronomic efficiency
      of the fertilizer application practice. An enrichment of the fertilizer-N of the
      order of 2% 15N abundance was sufficient to study N absorption rates and to
      establish fertilizer-N balances after one and two years of coffee cropping. The
      main source of errors in the estimated values lies in the inherent variability
      among field replicates and not in the measurements of N contents and 15N
      enrichments of plant material by mass-spectrometry.

PMID- 18066443
TI  - Anomalous origin of the right coronary artery: diagnosis and treatment.
AB  - We report the case of a rare anomaly of the right coronary artery (RCA) arising
      from the left aortic sinus, having a single ostium with the left coronary artery,
      associated with documented episodes of inferior ischemia, in which surgical
      treatment with a right internal thoracic artery to RCA bypass graft and the
      corresponding ligation provided greater stability to the coronary blood flow and
      good clinical progress.

PMID- 18066444
TI  - The ecosystem of cardiology guidelines--patrons of the state of the art in
      cardiology. Part I.

PMID- 18066445
TI  - Doppler echocardiographic flow pattern of the left internal thoracic artery
      following myocardial revascularization using a composite graft.

PMID- 18066446
TI  - Cardiac ventricular weights recorded at the autopsy of healthy subjects who died
      of external causes.
AB  - OBJECTIVE: To establish cardiac ventricular weights recorded during the autopsy
      of healthy individuals who died of external causes, aiming at determining
      normality patterns in our population. METHODS: A total of 94 hearts were
      evaluated at the Forensics Department of the city of Vitoria, Espirito Santo.
      After the heart removal and resection of the atria and epicardial fat, the right
      ventricle (RV) and the left ventricle (LV), including the septum, were separated
      and weighed and the mass was indexed by the height. The Kolmogorov-Smirnov test
      was used to test the normality of the distribution. Data are presented as means+/
      SD. RESULTS: After the exclusion of 12 hearts (possible cardiovascular disease
      detected post-mortem) 82 hearts were examined (52 males and 30 females, aged 16
      68 yrs, 31+/-12 yrs). The weight of the LV was 181+/-25 g and 125+/-15 g, and the
      weight of the RV was 54+/-7 g and 38+/-6 g; the LV mass indexed by height was
      105+/-14 g/m and 78+/-8 g/m, for males and females, respectively. The P95 of the
      LV weight was 218 g and 128 g/m in males and 148 g and 88 g/m in females. No
      significant correlation between ventricular mass and age was observed.
      CONCLUSION: The weight of the LV in the males from our sample was higher than
      that reported in the contemporary literature. Our results suggest that the
      presence of LV hypertrophy can be inferred in the presence of LV mass > 218 g or
      128 g/m in males and 148 g or 88 g/m in females.

PMID- 18066447
TI  - Atrial fibrillation ablation in Brazil: results of the registry of the Brazilian
      Society of Cardiac Arrhythmias.
AB  - BACKGROUND: Aiming to define the profile of curative atrial fibrillation (AF)
      ablation in Brazil, the Brazilian Cardiac Arrhythmia Society [Sociedade
      Brasileira de Arritmias Cardiacas] (SOBRAC) created the Brazilian Registry of AF
      Ablation [Registro Brasileiro de Ablacao da FA]. OBJECTIVE: To describe the
      results of this registry. METHODS: A questionnaire was sent to SOBRAC members
      asking about data on patients submitted to AF ablation between September 2005 and
      November, 2006. RESULTS: A total of 29 groups from 13 states completed the forms.
      Of these, 22 (76%) had performed AF ablations. Between 1998 and 2001, 7 groups
      (32%) initiated AF ablations and between 2002 and 2006, 15 groups began to
      perform them (68%). From 1998 to 2006, 2,374 patients were submitted to ablation,
      755 (32%) of them during the registry period. Most (70%) were males and 89%
      presented with paroxysmal or persistent AF. Ancillary imaging methods
      (intracardiac echocardiography and electroanatomic mapping) were used by 9 groups
      (41%). During an average five-month follow-up period, total success was 82% and
      success without use of antiarrhythmic agents was 57%. Nevertheless, 35% of the
      patients required two or more procedures. There were 111 complications (14.7%)
      and 2 deaths (0.26%). CONCLUSION: Curative AF ablation has been increasing
      significantly in our country, with success rates comparable to international
      indexes, but often more than one procedure is necessary. Despite promising
      results, AF ablation still results in significant morbidity. Supplementary
      imaging methods have been used more and more in an effort to increase efficacy
      and safety of the procedure. These findings should be considered by public and
      private funding agencies.

PMID- 18066448
TI  - Coronary artery disease in asymptomatic type-2 diabetic women. A comparative
      study between exercise test, cardiopulmonary exercise test, and dipyridamole
      myocardial perfusion scintigraphy in the identification of ischemia.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of morbidity and
      mortality among diabetic individuals. Myocardial ischemia is frequently
      asymptomatic, thus leading to a late diagnosis and worse prognosis. Diabetic
      women are known to have a cardiovascular death risk higher than that in men.
      OBJECTIVE: To assess the prevalence of coronary artery disease (CAD) in
      asymptomatic diabetic women. To compare the results of exercise test (ET),
      cardiopulmonary exercise test (CPET), and dipyridamole myocardial perfusion
      scintigraphy (MPS) with the findings of coronary angiography, (ANGI) in order of
      identify the most accurate method in the detection of significant CAD. METHODS: A
      total of 104 diabetic women were assessed with ET, CPET and MPS in the period
      within two months from the ANGI. MIBI-99mTc scintigraphy was performed using the
      gated-SPECT technique. Pearson's chi-square, Student's t tests were used for the
      statistical analysis and also the logistic regression analysis. RESULTS: The
      prevalence of CAD in the group studied was 32.7%. For the ET, an effective test
      (p=0.045), the chronotropic incompetence (p=0.031), and the exercise time
      performed (p=0.022) showed a significant association with DAC. For CPET, peak VO2
      and HR achieved were associated with CAD (p=0.004 and p=0.025, respectively).
      Most of the MPS variables showed a significant association with CAD (p=0.001, for
      all). CONCLUSION: The results obtained may suggest a high prevalence of CAD in
      diabetic women. Thus, this population should be investigated from the
      cardiovascular point of view even without cardiac symptom. Of the noninvasive
      diagnostic methods used, dipyridamole MPS was the one that showed the highest
      discrimination power in relation to diabetic women with CAD.

PMID- 18066449
TI  - Application of noninvasive ventilation in acute respiratory failure after
      cardiovascular surgery.
AB  - OBJECTIVE: To examine ventilatory response, oxygenation-related, and hemodynamics
      of patients with hypoxemic acute respiratory failure (ARF) submitted to
      noninvasive mechanical ventilation (NIV) during the postoperative phase of
      cardiovascular surgery in order to identify predictive variables of success, and
      to compare the different types of NIV. METHODS: Seventy patients with hypoxemic
      ARF were randomized to one of three modalities of NIV--continuous positive airway
      pressure (CPAP) and ventilation with two pressure levels (PEEP + SP and BiPAP).
      Ventilation, oxygenation-related, and hemodynamics variables were analyzed at pre
      application, and 3, 6, and 12 hours after the protocol began. RESULTS: Thirteen
      patients were excluded. Thirty-one patients progressed to independence from
      ventilatory support and comprised the success group, and 26 required orotracheal
      intubation and were considered the nonsuccess group. Age, initial heart rate
      (HR), and respiratory rate (RR) showed elevated levels in the nonsuccess group
      (p=0.042, 0.029, and 0.002, respectively). A greater number of intraoperative
      complications were seen in the nonsuccess group (p=0.025). Oxygenation variables
      increased only in the success group. Among the NIV types, 57.9% of patients in
      the ventilator group, 57.9% in the two-pressure levels group, and 47.3% in the
      CPAP group progressed with success. Oxygenation and RR variables showed
      improvement only in the groups with two pressure levels. CONCLUSION: Patients
      with hypoxemic ARF in the postoperative stage after cardiovascular surgery showed
      better oxygenation, RR, and HR during NIV application. In older patients and
      those with higher baseline RR and HR values, NIV was not sufficient to reverse
      ARF. The two-pressure level modes showed better results.

PMID- 18066450
TI  - Prevalence of coronary risk factors and myocardial perfusion scintigraphy
      abnormalities in asymptomatic diabetic outpatients.
AB  - OBJECTIVE: To determine the prevalence of coronary artery disease (CAD) risk
      factors (RF) and myocardial ischemia in a sample of asymptomatic diabetic
      patients treated on an outpatient basis. METHODS: From 80 type 2 diabetic
      patients initially recruited at an university outpatient endocrinology clinic,
      with no symptoms and/or CAD diagnosis, only 61 patients completed the study
      protocol, being 52,5% females, with a mean age of 56.3 +/- 10.9 years. The
      patients were interviewed searching for RF and underwent electrocardiogram,
      echocardiogram and perfusional myocardial scintigraphy (PMS) at rest and under
      stress. According to the PMS results they were divided into two groups: an
      ischemic and a normal one . RESULTS: The RF identified were: male gender (48%),
      age > or = 55 years (51%), family history of premature atherosclerotic disease
      (16%), history of smoking (46%), hypertension (44%), sedentary lifestyle (62%),
      overweight/obesity (67%), HDL- cholesterol < 45 mg/dl (69%), LDL- cholesterol >
      or = 100 mg/dl (85%) and triglycerides > or = 150 mg/dl (54%). Ischemic MPS were
      diagnosed in 15% of the patients. The variables associated with this diagnosis
      were: male gender (p=0.007), low HDL levels (p=0.046), history of smoking
      (p=0.038), left ventricular hypertrophy (LVH) (p=0.043) and left ventricle
      ejection fraction (LVEF) < 60% (p=0.01). CONCLUSION: A high prevalence of
      associated RF was observed, as well as a significant prevalence of 15% for
      myocardial ischemia. The variables identified as predictors of a myocardial
      ischemia diagnosis were: male gender, low HDL-cholesterol, past smoking, LVH and
      LVEF < 60%.

PMID- 18066451
TI  - Silent myocardial ischemia in patients with stable coronary artery disease
      receiving conventional antianginal drug therapy.
AB  - BACKGROUND: Few data are available on the behavior of myocardial ischemia during
      daily activities in patients with coronary artery disease receiving antianginal
      drug therapy. OBJECTIVE: To study the mechanism generating myocardial ischemia by
      evaluating blood pressure and heart rate changes in patients with stable
      atherosclerotic disease receiving drug therapy and with evidence of myocardial
      ischemia. METHODS: Fifty non-hospitalized patients (40 males) underwent 24-hour
      electrocardiographic monitoring synchronized with blood pressured monitoring.
      RESULTS: Thirty five episodes of myocardial ischemia were detected in 17
      patients, with a total duration of 146.3 minutes; angina was reported in five
      cases. Twenty nine episodes (100.3 minutes) occurred during wakefulness, with 11
      episodes (35.3 + 3.7 min) in the period from 11 a.m. to 3 p.m. Blood pressure and
      heart rate evaluation in the three ten-minute intervals following the ischemic
      episodes showed a statistically significant difference (p< 0.05), unlike that
      shown for the three intervals preceding the episodes. However, during the
      ischemic episode, a higher than 10-mmHg elevation in blood pressure and 5 beats
      per minute in heart rate were observed when compared with the time interval
      between 20 and 10 minutes before the episode. The mean heart rate at the onset of
      ischemia during the exercise test performed before the study was 118.2 + 14.0,
      and 81.1 + 20.8 beats per minute on the 24-hour electrocardiogram (p < 0.001).
      CONCLUSION: The incidence of silent myocardial ischemia is high in stable
      coronary artery disease and is related to alterations in blood pressure and heart
      rate, with different thresholds for ischemia for the same patient.

PMID- 18066452
TI  - Prevalence of cardiovascular risk factors in adults living in Luzerna, Santa
      Catarina, in 2006.
AB  - OBJECTIVES: To estimate the prevalence of cardiovascular risk factors in the
      adult population of Luzerna, in the state of Santa Catarina. METHODS: A cross
      sectional study with adults of both genders aged 20 to 59 years (n = 411). The
      prevalence of hypertension, diabetes, dyslipidemia, obesity, increased waist
      circumference, and smoking was estimated. Study variables were checked for
      frequency distribution, and a chi-square test for association was performed.
      RESULTS: The response rate was 85.9%. The following prevalences were found:
      hypertension: 14.7%; diabetes: 2.3%; dyslipidemia: 18.7%; obesity: 15.6%;
      increased waist circumference: 24.1%; and smoking: 15.6%. A total of 52.4% of the
      subjects had none of the risk factors; 22.4% had one risk factor, and 13.6%,
      6.8%, and 4.9% had two, three, and four or more associated risk factors,
      respectively. CONCLUSION: The study sample showed low prevalence of hypertension
      and diabetes and less clustering of risk factors in the same individual, as
      compared with other data reported in the literature.

PMID- 18066453
TI  - Efficacy of atorvastatin when not administered daily.
AB  - BACKGROUND: Statins are widely used because they reduce cardiac events. Although
      they are indicated for daily use, some doctorsgive prescriptions for every other
      day, mainly with the purpose of reducing costs. OBJECTIVE: To evaluate the
      efficacy of atorvastatin, when not administered everyday, on LDL-cholesterol (LDL
      C) levels, and also to evaluate cost reduction. METHODS: A total of 100 patients
      with hypercholesterolemia in primary (PP) and secondary prevention (SP) were
      assessed. After a 12-week diet period, atorvastatin was initiated at a dose of 10
      mg per day. After six weeks, LDL-C was determined, and if the levels were <80 or
      <104 mg/dL for SP and PP, respectively, two atorvastatin doses were subtracted
      per week. If LDL-C remained <80 or <104 mg/dL, a further reduction to three times
      a week was allowed, and the last determination was performed after six more
      weeks. The percentage variation in costs was the parameter to evaluate the
      saving. RESULTS: In 47 out of the 52 patients of this group, a reduction by 32%
      in LDL-C was observed, and daily atorvastatin was maintained. Forty one patients
      remained throughout the study and had their weekly dosage reduced. In 25 patients
      the medication was administered three times a week, and in 16, five times a week,
      with reductions of 42.4% and 46.1% in LDL-C, respectively. As regards costs, one
      of the groups had their monthly expense reduced from R$ 106.65 to R$ 74.65, and
      the other group from R$ 106.65 to R$ 53.33. CONCLUSION: The results suggest that
      atorvastatin may be administered on a non-daily basis. A cost reduction between
      30% and 50% was also observed.

PMID- 18066454
TI  - Exposition to smoking and attitudes: comparison between inquiries applied to
      adult population in Sao Paulo City, 1987 and 2002.
AB  - BACKGROUND: Periodic monitoring of tobacco smoking in the population is of public
      health interest. OBJECTIVES: To compare the prevalence of smoking habits and
      attitudes toward tobacco smoking from a sample of residents of the City of Sao
      Paulo, in 1987 and 2002. METHODS: Two random sampling household surveys were
      carried out among residents of the City of Sao Paulo, in 1987 and 2002,
      respectively with 1,471 and 2,103 participants aged 15-59 years RESULTS: Age
      adjusted prevalence of tobacco smoking dropped from 41.8% (in 1987) to 25.5% (in
      2002) among males and, respectively, from 30.6% to 19.8% among females, and such
      reduction was observed in all education levels. There was a decrease in the mean
      number of cigarettes smoked a day among men (but an increase among women), There
      was a growth in the preference for low tar cigarettes, an increase in those who
      quit smoking in the last 10 years, a growth among those who seriously tried to
      quit smoking, and an increase in those who believe in that "smoking is dangerous
      for your health". CONCLUSION: There was a favorable change in the situation of
      smoking habits in the City of Sao Paulo from 1987 to 2002.

PMID- 18066455
TI  - Case 6/2007: a ten-year-old child with mild pulmonary valve stenosis.

PMID- 18066456
TI  - Use of mechanical circulatory support in cases of end-stage acute heart failure.

PMID- 18066457
TI  - Ambulatory blood pressure monitoring and type 2 diabetes mellitus.
AB  - Hypertension is one of the main risk factors for the onset and progression of
      chronic complications in type 2 diabetes mellitus (DM). Ambulatory blood pressure
      (BP) monitoring (ABPM) provides a better correlation with target organ lesions
      than BP obtained in the office. Furthermore, it allows the evaluation of distinct
      BP parameters such as the 24-h, daytime and nighttime systolic and diastolic BP
      means, BP loads and the absence of nocturnal drop of BP, as well as the
      identification of white-coat and masked hypertension. DM patients have higher
      daytime and nighttime BP means than non-DM patients. In addition, one third of
      normotensive type 2 DM patients have masked hypertension, which is associated
      with an increase in albuminuria and in left ventricle wall thickness. On the
      other hand, the prevalence and effect of white-coat hypertension in type 2 DM
      patients have not yet been properly evaluated. The absence of nocturnal drop of
      BP does not add information to the 24 h, daytime or nighttime BP measurements,
      but the nighttime BP means seem to be relevant in DM retinopathy. In conclusion,
      BP determination by ABPM allows better patient risk stratification for the
      development of DM chronic complications and is an essential instrument for
      effective BP control in these patients.

PMID- 18066460
TI  - [Oswaldo Paulo Forattini: epidemiologist, entomologist and humanist].

PMID- 18066462
TI  - [Infestation of an urban area by Aedes aegypti and relation with socioeconomic
      levels].
AB  - OBJECTIVE: To assess the association between Aedes aegypti larvae infestation
      rates and socioeconomic factors. METHODS: Infestation rates in the urban area of
      the city of Sao Jose do Rio Preto, Southeastern Brazil, were calculated in
      January of 2005 and subsequently geocoded by address. The urban census tracts
      were grouped by means of main component analysis, thus producing four
      socioeconomic clusters (1-4, in a decreasing order of socioeconomic level) and a
      fifth cluster (5) with a level below the others and not belonging to the urban
      census tracts (new districts and irregular residential development projects). The
      Breteau index (BI), the house index (HI), and the container index (CI), as well
      as the averages of existing containers surveyed per home, were calculated for
      each cluster. RESULTS: The values of infestation indices did not show significant
      differences among socioeconomic clusters 1 to 4, even though they were lower than
      the indices obtained for cluster 5. The averages of existing containers surveyed
      were higher for cluster 1 in relation to clusters 2 to 4, but did not show
      significant differences when compared to cluster 5. CONCLUSIONS: Larval indices
      did not show association with the different socioeconomic levels of the cluster
      that corresponds to the urban census tracts. Nonetheless, new districts,
      irregular residential development projects and locations adjacent to those with
      the worst basic sanitary conditions showed the highest values for these
      indicators.

PMID- 18066463
TI  - [Socioeconomic variables and dengue transmission].
AB  - OBJECTIVE: To evaluate the relationship between risk of occurrence of dengue and
      socioeconomic level. METHODS: All confirmed autochthonous cases of dengue between
      September 1990 and August 2002 were geocoded and grouped according to the urban
      census tracts of the municipality of Sao Jose do Rio Preto, Southeastern Brazil.
      A socioeconomic factor generated by principal component analysis was used to
      group census tracts into four socioeconomic levels. Incidence rates were
      calculated for each year and four-year period for each of the census sectors,
      considering the period from September of one year to August of the next. Thematic
      maps of sectors, grouped into each of the four socioeconomic levels and their
      respective disease incidences, are presented. RESULTS: Principal component
      analysis generated a socioeconomic factor that accounted for 87% of total
      variation. This factor was associated with dengue incidence only for the 1994-95
      period. CONCLUSIONS: The lack of an association between risk of occurrence of
      dengue and socioeconomic levels in almost all years studied indicates that this
      issue deserves further study, and may vary depending on the settings found in
      each municipality. It will be important to determine the spatial relationship
      between dengue transmission and other variables, such as degree of immunity in
      the population, effectiveness of control measures, degree of infestation by the
      vector; and population habits and behaviors, among others.

PMID- 18066464
TI  - [Analysis of visceral leishmaniasis reports by the capture-recapture method].
AB  - OBJECTIVE: To analyze the number of cases, deaths, incidence and fatality rate
      due to visceral leishmaniasis, and to estimate its underreporting, as well as the
      coverage of the national information systems. METHODS: Confirmed cases of
      visceral leishmaniasis were analyzed, based on the following systems: the Sistema
      de Informacao de Agravos de Notificacao (SINAN - Information System on Disease
      Notification), the Sistema de Informacoes sobre Mortalidade (SIM - Mortality
      Information System) and the Sistema de Informacoes Hospitalares (SIH - Hospital
      Information System), between 2002 and 2003. The variables utilized in
      relationship for pair identification were: patient's name, mother's name, date of
      birth, gender, city of residence, and mailing address. The capture-recapture
      method was applied to calculate the estimates, by means of the Chapman formula.
      RESULTS: The estimated underreporting of visceral leishmaniasis in the SINAN, in
      relation to the SIH and the SIM, was 42.2% and 45.0% respectively. The estimated
      underreporting of deaths was 53% and 46.5%, when compared to SINAN-deaths and SIH
      deaths respectively. The estimated incidence was 2.9 per 100,000 inhabitants,
      from the comparison between the SINAN and the SIH, 70.5% higher than the one
      found when SINAN's data were the only ones utilized. Furthermore, when comparing
      data from SIM and SINAN-deaths, an estimated fatality rate of 8% was observed,
      representing an increase in 16% from the one initially registered in the SINAN
      deaths. CONCLUSIONS: The results show high estimated underreporting of cases and
      deaths due to visceral leishmaniasis in Brazil. The relationship between
      information systems and the capture-recapture method application enabled to know
      and improve the epidemiological estimates, making its utilization in health
      services feasible.

PMID- 18066465
TI  - [Validity of self-reported diabetes and its determinants: evidences from the
      Bambui study].
AB  - OBJECTIVE: To assess the validity of self-reported diabetes and its determinants
      in the elderly. METHODS: Cross-sectional study including 1,492 subjects aged >or=
      60 years, which corresponds to 86% of all residents in this age group living in
      the municipality of Bambui, Southeastern Brazil, in 1997. The validity of self
      reported diabetes was assessed comparing to diabetes mellitus defined by medical
      criteria (fasting glucose > 126 mg/dl or current treatment). Multivariate
      analysis was carried out to assess factors independently associated with
      sensitivity and specificity. RESULTS: The prevalence of diabetes mellitus and
      self-reported diabetes were 14.5% and 11.7%, respectively. Sensitivity and
      specificity of self-reported diabetes were 57.1% (95% CI: 50.3;63.8) and 96.9%
      (95% CI: 94.7;97.0), respectively. Medical visits in the previous two years
      (PR=3.78), as well as 1-3 (PR=1.90) and > 4 years (PR=1.55) of schooling were
      positively and independently associated with sensitivity. Medical visits in the
      previous two years (PR= 0.96) and female sex (PR = 0.97) were negatively and
      independently associated with specificity. CONCLUSIONS: The study results
      indicated that self-reported diabetes should not be either used to estimate the
      prevalence of diabetes mellitus or to identify individuals with the disease in
      the study population. Schooling and medical visits were determinants of the
      elderly awareness of being diabetics, indicating that these modifiable
      characteristics may play a role in secondary and tertiary prevention.

PMID- 18066466
TI  - [Use of theories and models on papers of a Latin-American journal in public
      health, 2000 to 2004].
AB  - OBJECTIVE: To characterize frequency and type of use of theories or models on
      papers of a Latin-American journal in public health between 2000 and 2004.
      METHODS: The Revista de Saude Publica was chosen because of its history of
      periodic publication without interruption and current impact on the scientific
      communication of the area. A standard procedure was applied for reading and
      classifying articles in an arbitrary typology of four levels, according to the
      depth of the use of models or theoretical references to describe problems or
      issues, to formulate methods and to discuss results. RESULTS: Of 482 articles
      included, 421 (87%) were research studies, 42 (9%) reviews or special
      contributions and 19 (4%) opinion texts or assays . Of 421 research studies, 286
      (68%) had a quantitative focus, 110 (26%) qualitative and 25 (6%) mixed.
      Reference to theories or models is uncommon, only 90 (19%) articles mentioned a
      theory or model. According to the depth of the use, 29 (6%) were classified as
      type I, 9 (2%) as type II, 6 (1.3%) were type III and the 46 remaining texts
      (9.5%) were type IV. CONCLUSIONS: Reference to models was nine-fold more frequent
      than the use of theoretical references. The ideal use, type IV, occurred in one
      of every ten articles studied. It is of relevance to show theoretical and models
      frames used when approaching topics, formulating hypothesis, designing methods
      and discussing findings in papers.

PMID- 18066467
TI  - [Violence against women, family cohesion and drugs].
AB  - OBJECTIVE: To evaluate the association between cohesion, adaptability and mental
      risk in families, physical violence against women and the use of drugs. METHODS:
      Data for this paired case-control study was collected in 2004 and 2005 in the
      city of Joao Pessoa, in Northeastern Brazil. The sample included 260 women,
      divided into 130 battered individuals and 130 non-battered. The case study group
      consisted of women who lodged complaints for domestic violence at the Specialist
      Women's Police Station. The control group was made up of women living in the same
      neighborhood as those who had made the complaint. Cohesion, adaptability and
      mental risk were all measured using the "Family Adaptability and Cohesion
      Evaluation Scales". For the statistical analysis the Chi-square and the Fisher's
      Exact Tests ere used, at a significance level of 5%. RESULTS: The two groups
      differed for measures relating to mental risk and cohesion, but had similar
      results for family adaptability (p=0.0917). The women victims of domestic
      violence had high (43.1%) and medium (39.2%) mental risk, while the non-victims
      had only medium risk (55.4%). There was a significant difference in drug use
      between the two groups, with greater consumption among the families of battered
      women (90.8%) compared with those of non-battered women (56.9%). The most widely
      used drug was alcohol, which also represented the highest risk factor for
      aggression if consumed daily (OR=37.33) or in conjunction with other drugs
      (OR=29,56). CONCLUSIONS: Both the instability caused by a lack of family unity
      and the use of drugs significantly affect family functioning and may give rise to
      conflict and domestic violence.

PMID- 18066468
TI  - [Food intake during pregnancy and postpartum according to skin color in Rio de
      Janeiro, Brazil].
AB  - OBJECTIVE: To assess dietary intake during pregnancy and postpartum according to
      skin color. METHODS: A longitudinal prospective study was carried out comprising
      467 postpartum women aged between 15-45 years in the city of Rio de Janeiro,
      Southeastern Brazil, in 1999-2001. A food frequency questionnaire was
      administered at two weeks postpartum (intake covering the pregnancy period) and
      at six months postpartum (intake covering the postpartum period). Analysis of
      covariance was performed to evaluate differences in food intake among skin color
      groups, adjusted for educational level. RESULTS: During pregnancy, black and
      mulatto women had 13.4% and 9.1% higher energy intake (p=0.009 and p=0.028) and
      15.1% and 10.5% higher carbohydrate intake (p=0.005 and p=0.014) than white
      women, respectively. Energy intake of black and white women exceeded the
      nutritional recommendations by 34% and 20%, respectively (p=0.035). During the
      postpartum period, black women had 7.7% higher energy intake (p=0.030) and 14.8%
      higher lipid intake (p=0.008) than white women, as well as 23.8% and 13% higher
      saturated fatty acids intake than white (p = 0.003) and mulatto (p = 0.046)
      women, respectively. The adequacy of lipid and saturated fatty acids intake was
      higher in black (p=0.024) than white women (p=0.011). CONCLUSIONS: The study
      suggests the need to revise nutritional interventions strategies in the prenatal
      period, and to implement nutritional guidance programs during the postpartum
      period in order to adjust food intake to adequate levels, taking into
      consideration racial differences identified.

PMID- 18066469
TI  - [Factors associated to the evolution of gestational weight of pregnant women: a
      multilevel analysis].
AB  - OBJECTIVE: To assess the influence of socioeconomic, reproductive, and behavioral
      factors on the evolution of weight during pregnancy. METHODS: Body weight was
      measured prospectively in a cohort of 215 healthy pregnant women attended to by a
      public prenatal service in the city of Sao Paulo, between 1997 and 1998. The
      criteria for inclusion were the following: aged 18 or older and with the
      beginning of prenatal care at a gestational age <or= 16 weeks. The relation
      between the independent variables and the evolution of weight during pregnancy
      was assessed by means of the multilevel hierarchical linear analysis, and
      subsequently analyzed by the maximum likelihood test. RESULTS: In the multilevel
      analysis, the factors that were significantly associated to gestational weight
      gain were the following: initial BMI, level of education, marital status and
      parity. The equations thus obtained enabled to identify the individual effect of
      each of these characteristics: eutrophic initial BMI, level of education >or= 4
      years, lack of partner, and primiparity cause increases of 3.0 kg, 1.9 kg, 2.3 kg
      and 2.4 kg in the total weight gain during pregnancy, respectively. CONCLUSIONS:
      Initial BMI, level of education and parity are the maternal characteristics that,
      along with the marital status, must be taken into consideration in the
      development of strategies to promote adequate weight gain during pregnancy.

PMID- 18066470
TI  - [Health care and mortality of very-low-birth-weight neonates].
AB  - OBJECTIVE: To assess inpatient mortality rate of very-low-birth-weight neonates,
      their clinical progression and factors associated with mortality. METHODS:
      Longitudinal study including 360 neonates weighing 500-1500 g who were born in
      Londrina, Southern Brazil, from January 1, 2002 to June 30, 2004. Data were
      collected through interviews with the mothers and from medical records and follow
      up of neonates during hospitalization. Chi-square test was used to determine the
      association between variables. Statistically significant variables were selected
      to the logistic regression model and the level of significance adopted was 5%.
      RESULTS: Mortality rate was 32.5%. In bivariate analysis, the following variables
      were associated with death: no prenatal use of corticosteroids; no
      hypertension/preeclampsia; labor; vaginal delivery; non-cephalic presentation;
      Apgar scores <or= 3 at the first and fifth minutes; Clinical Risk Index for
      Babies score > 5; male sex; weight < or=750 g; gestational age < 28 weeks;
      resuscitation procedures in the delivery room; respiratory distress syndrome;
      pneumothorax; intracranial hemorrhage; and mechanical ventilation. In the
      logistic regression, the following variables were still considered risk factors:
      low income; no prenatal use of corticosteroids; no use of continuous positive
      airway pressure. CONCLUSIONS: Despite technology advances, very-low-birth-weight
      neonates mortality is high in Brazil compared with developed countries. Prenatal
      use of corticosteroids should be encouraged to reduce morbidity and mortality of
      very-low-birth-weight neonates.

PMID- 18066471
TI  - [Risk factors for early neonatal mortality].
AB  - OBJECTIVE: To assess risk factors for early neonatal mortality. METHODS: A
      population-based case-control study was carried out with 146 early neonatal
      deaths and a sample of 313 controls obtained among survivals of the neonate
      period in the south region of the city of Sao Paulo, in the period of 8/1/2000 to
      1/31/2001. Information was obtained through home interviews and hospital charts.
      Hierarchical assessment was performed in five groups with the following
      characteristics 1) socioeconomic conditions of mothers and families, 2) maternal
      psychosocial conditions, 3) obstetrical history and biological characteristics of
      mothers, 4) delivery conditions, 5) conditions of newborns RESULTS: Risk factors
      for early neonate mortality were: Group 1: poor education of household head
      (OR=1.6; 95% CI: 1.1;2.6), household located in a slum area (OR=2.0; 95% CI:
      1.2;3.5) with up to one room (OR=2.2; 95% CI: 1.1;4.2); Group 2: mothers in
      recent union (OR=2.0; 95% CI: 1.0;4.2), unmarried mothers (OR=1.8; 95% CI:
      1.1;3.0), and presence of domestic violence (OR=2.7; 95% CI: 1;6.5); Group 3:
      presence of complications in pregnancy (OR=8.2; 95% CI: 5.0;13.5), previous low
      birth weight (OR=2.4; 95% CI: 1.2;4.5), absence of pre-natal care (OR=16.1; 95%
      CI: 4.7;55.4), and inadequate pre-natal care (block 3) (OR=2.1; 95% CI: 2.0;3.5);
      Group 4: presence of clinical problems during delivery (OR=2.9; 95% CI: 1.4;5.1),
      mothers who went to hospital in ambulances (OR=3.8; 95% CI: 1.4;10.7); Group 5:
      low birth weight (OR=17.3; 95% CI: 8.4;35.6) and preterm live births (OR=8.8; 95%
      CI: 4.3;17.8). CONCLUSIONS: Additionally to proximal factors (low birth weight,
      preterm gestations, labor complications and unfavorable clinical conditions in
      gestation), the variables expressing social exclusion and presence of
      psychosocial factors were also identified. This context may affect the
      development of gestation and hinder the access of women to health services.
      Adequate prenatal care could minimize the effect of these variables.

PMID- 18066472
TI  - [Infant mortality and sociodemographic conditions in Ceara, Brazil, 1991 and
      2000].
AB  - OBJECTIVE: To assess ecological models to describe infant mortality rate in Ceara
      (Northeastern Brazil) in two different periods of time. METHODS: This was a cross
      sectional ecologic study of two years, 1991 and 2000, using non-matching
      information per municipalities. Estimates on the infant mortality rate of the
      Instituto de Pesquisas Economicas Aplicadas (Institute of Applied Economic
      Research) have been used. For the remaining indicators different sources of the
      System of Health Information were used. The main risk factors were assessed using
      multiple linear regression. RESULTS: In 1991, the variables that predicted infant
      mortality rate (R2=0.3575) were: small houses (beta=0.0043; rho=0.010),
      proportion of inhabitants with tap water in the household (beta=-0.0029;
      rho=0.024), urbanization rate (beta=0.0032; rho=0.004), fecundity rate
      (beta=0.0351; rho=0.024), the proportion of children working at 10-14 years
      (beta=0.0049; rho=0.017), proportion of families with income < 1/2 minimum wage
      (beta=0.0056; rho=0.000), that can read and write (beta=-0.0062; rho=0.031). In
      the year 2000, the following possible determinants were identified (R2=0.3236):
      the proportion of children <2 years of age with malnutrition (beta=0.0064;
      rho=0.024), proportion of households with adequate sanitation (beta=-0.0024;
      rho=0.010), proportion of women who could read and write (beta=-0.0068;
      rho=0.044), expenses on health human resources regarding total health expenses
      (beta=-0.0024; rho=0.027), proportion of the value of the vegetal production in
      relation to the total of the state (beta=-0.1090; rho=0.001), intensity of
      poverty (beta=0.0065; rho=0.002), and ageing index (beta=-0.0100; rho=0.006).
      CONCLUSIONS: Although the variables have not been exactly the same for the
      evaluated period, determiners of infant mortality have been changing, except for
      indicators of education, income and sanitation. The overall decrease in fecundity
      led to a reduction in its discriminating power, and it was replaced by the ageing
      index. Another tendency observed was the replace of several demographic variables
      by health care indicators.

PMID- 18066473
TI  - [Adverse events following diphtheria, pertussis and tetanus vaccinations and
      factors associated with severity].
AB  - OBJECTIVE: To analyze adverse events following vaccinations against diphtheria,
      pertussis and tetanus (AEFV-DPT) and to investigate factors associated with event
      severity. METHODS: A cross-sectional study was carried out with a descriptive and
      analytical component covering AEFV-DPT that were notified in the State of Sao
      Paulo, Brazil, between 1984 and 2001, among children less than seven years old.
      Cases were defined as used in AEFV-DPT surveillance; the data source was AEFV-DPT
      passive surveillance. In calculating the rates, the numerator was the number of
      AEFV-DPT and as denominator was the number of doses applied. The association
      between severity of AEFV-DPT and the exposures of interest was investigated by
      means of non-adjusted and adjusted estimates of odds ratios, with their
      respective 95% confidence intervals, using non-conditional logistic regression.
      RESULTS: A total of 10,059 AEFV-DPT were identified, corresponding to 6,266
      children who presented one or more AEFV-DPT, 29.5% were hospitalized and 68.2%
      presented contraindications for subsequent DPT doses. Around 75% of the events
      occurred during the first six hours after vaccination. The most frequent AEFV-DPT
      were: fever < 39.5 degrees C, local reactions, hypotonic-hyporesponsive episodes
      and convulsion. Time interval of less than one hour between vaccination and the
      event (OR = 2.1), first dose applied (OR=5.8) and previous personal (OR=2.2) and
      family (OR=5.3) neurological histories were independently associated with severe
      events. CONCLUSIONS: Passive surveillance of AEFV-DPT was shown to be useful for
      monitoring the safety of the DPT vaccine, through describing the characteristics
      and magnitude of these events, and also enabling identification of possible
      factors associated with severe forms.

PMID- 18066474
TI  - [Reproducibility and validity of a food consumption questionnaire for
      schoolchildren].
AB  - The aim of the study was to assess the reproducibility and validity of the
      previous day food questionnaire (PDFQ) for schoolchildren. The questionnaire is
      illustrated with 21 foods and was designed for use at group level. The
      participants were 131 schoolchildren aged eight to ten years who were studying
      full-time in a public school in a city of Southern Brazil, in 2005.
      Reproducibility was assessed by applying the questionnaire twice on the same day.
      Validity was assessed by comparing the food items selected on the questionnaire
      and direct observations from three school meals on the previous day. The
      questionnaire presented high sensitivity, ranging from 73.4% (beans) to 95.5%
      (rice), and high specificity, ranging from 87.3% (fruits) to 98.8% (beans). It
      was concluded that the questionnaire was capable of generating reproducible and
      valid data for assessing the food intake of schoolchildren on the previous day.

PMID- 18066475
TI  - Iranian casualties during the eight years of Iraq-Iran conflict.

PMID- 18066476
TI  - [59th SBPC National Meeting: Amazon - National Challenge in Belem, 2007].

PMID- 18066477
TI  - [Adolfo Lutz Institute: testing of a quality assurance program in hematology and
      biochemistry].

PMID- 18066478
TI  - [External quality control in cervical cytopathology: an evaluation from 2000
      2004].

PMID- 18066479
TI  - The ADMIT series - issues in inhalation therapy. 1) The goals of asthma
      treatment: can they be achieved?
AB  - The widespread use of inhaled corticosteroids (ICS) since the early 1970's has
      meant that asthma is generally better controlled in comparison with previous
      decades. Nevertheless, recent patient interview surveys indicate that there is
      still a lot to gain in terms of abolishing daytime and nocturnal symptoms, and
      asthma exacerbations. It is important to use the terms asthma 'control' and
      asthma 'severity' in a correct way. Whereas asthma control reflects fluctuation
      in symptoms and lung function (or lack of them) over time, asthma severity
      reflects both asthma control and the need for medication. Thus, 'severity' is a
      property of the disease which reflects the degree of pathophysiological
      abnormality, whereas 'control' refers to the reduction of the clinical
      manifestations of disease achieved by treatment - thereby reflecting the adequacy
      of treatment. This introductory review, the first of a series of review papers to
      be published in this journal by the ADMIT team (see Appendix), discusses briefly
      our present knowledge of asthma control, its components, factors that may limit
      patients' ability to achieve optimal asthma control, and instruments to measure
      asthma control.

PMID- 18066480
TI  - Issues in inhalation therapy: a new series of papers from the ADMIT Working
      Group.

PMID- 18066481
TI  - Initial temporary misdiagnosis of bronchiectasis following pumpkin seed
      aspiration.
AB  - Undiagnosed and retained foreign bodies may result in serious complications such
      as pneumonia, atelectasis, or bronchiectasis. In this report, the authors present
      a rare case of temporary bronchiectasis of the left lung due to a long-standing
      retained foreign body in a child. Interestingly, the whole left lung was affected
      due to the check valve type of obstruction of the main bronchus. Unexpected,
      unilateral findings on a chest x-ray or a CT scan could be related to an inhaled
      foreign body, and any delay in making the diagnosis may result in serious
      complications.

PMID- 18066483
TI  - The "normal" mobility of the urethra.

PMID- 18066482
TI  - Efficacy of tolterodine in relation to different urodynamic findings of detrusor
      overactivity.
AB  - Aim of the study was to evaluate the efficacy of tolterodine in relation to
      different urodynamic findings of detrusor overactivity (DO). Women with
      urodynamic diagnosis of DO were prospectively included into two groups: with
      involuntary detrusor contractions during the cystometric filling phase (group 1)
      or after provocative manoeuvres (group 2). Tolterodine 4 mg ER was prescribed to
      all women. Drug efficacy was assessed using a 3-point scale. Women were defined
      responders if they were improved/cured after 3 months of therapy, and non
      responders if symptoms did not change. The outcome of therapy was compared
      between groups. A total of 111 women were included. The groups did not differ for
      demographic characteristics. After 12 weeks, we found a significant difference (P
      = 0.0008) between groups in terms of tolterodine efficacy with a better response
      rate in group 1. Our study shows that tolterodine efficacy may be related to
      different urodynamic findings of DO.

PMID- 18066484
TI  - Economic implications of osteoporosis-related femoral fractures in Saudi Arabian
      society.
AB  - PURPOSE: To assess the prevalence of proximal femoral fractures due to osteopenia
      and osteoporosis in the eastern province of Saudi Arabia and to estimate the cost
      of management of osteoporosis-related femoral fractures. METHODS: This is a
      retrospective study of all patients admitted to the orthopaedic department of the
      King Fahd Hospital of the University, AlKhobar between January 2001 and December
      2006. There were 63 patients admitted to the hospital with osteoporosis-related
      fractures and 43 sustained proximal femoral fractures. The cost of management of
      these patients from admission to discharge was analyzed. A verbal survey was
      carried with all the hospitals in the eastern province to establish the
      prevalence of osteoporosis-related femoral fractures for a 12 month period.
      RESULTS: There were 23 male and 20 female patients with average age of 72.11
      years and the hospital stay was for 760 days. The cost of managing these patients
      was SR2.09 million (US$557,333.00) at the rate of SR48,712 (US$12,989.90) per
      patient. The survey of all hospitals in the eastern province of Saudi Arabia
      showed that 984 proximal femoral fractures occurred in a population of 164,121.
      The estimated cost was SR48 million (US$12.78 million) annually. On a national
      basis, with a population of 1,461,401 Saudis aged 50 years or more, 8,768 would
      suffer femoral fractures yearly at a cost of SR4.27 billion (US$1.14 billion).
      CONCLUSION: This study raises serious economic concerns. The annual cost of
      management of osteoporosis-related proximal femoral fractures in the eastern
      province of Saudi Arabia is US$12.78 million. As the Saudi Arabian population is
      aging and the number of elderly patients is bound to increase, with an
      accompanying increase in fractures, the impact on health care budgets will be
      tremendous.

PMID- 18066485
TI  - Relationship of geographic distance, depth, temperature, and viruses with
      prokaryotic communities in the eastern tropical Atlantic Ocean.
AB  - The richness and biogeographical distribution pattern of bacterial and archaeal
      communities was assessed by terminal restriction fragment length polymorphism
      analysis of polymerase chain reaction-amplified fragments of the 16S rRNA gene at
      the surface (15-25 m depth), in the deep chlorophyll maximum layer (DCM; 50 m
      depth), and deep waters (75-1000 m depth) of the eastern tropical Atlantic Ocean.
      Additionally, prokaryotic and viral abundance and the frequency of infected
      prokaryotic cells (FIC) were determined along with physico-chemical parameters to
      identify factors influencing prokaryotic richness and biogeography. Viral
      abundance was highest in the DCM layer averaging 45.5 x 10(6) ml(-1), whereas in
      the mixed surface layer and in the waters below the DCM, average viral abundance
      was 11.3 x 10(6) and 4.3 x 10(6) ml(-1), respectively. The average estimate of
      FIC was 8.3% in the mixed surface layer and the DCM and 2.4% in deeper waters.
      FIC was positively related to prokaryotic and viral abundance and negatively to
      archaeal richness. There was no detectable effect of geographic distance (maximum
      distance between stations approximately 4600 km) or differences between water
      masses on bacterial and archaeal community composition. Bacterial communities
      showed a clear depth zonation, whereas changes in archaeal community composition
      were related to temperature and FIC. The results indicate that planktonic
      archaeal virus host systems are a dynamic component of marine ecosystems under
      natural conditions.

PMID- 18066487
TI  - Immediate (0-6 h), early (6-72 h) and late (>72 h) complications after anterior
      cervical discectomy with fusion for cervical disc degeneration; discharge six
      hours after operation is feasible.
AB  - OBJECTIVES: The introduction of minimally invasive techniques and total
      intravenous anaesthesia has led to reports of the performance of anterior
      cervical discectomy and fusion as an outpatient. The safety of this approach,
      requires information about the complications presenting within this period. The
      aim of this study was to assess the rates and types of immediate (0-6 h), early
      (6-72 h) and late (>72 h) complications after anterior cervical discectomy with
      fusion. METHODS: We prospectively studied complications after anterior cervical
      discectomy with fusion in patients with degenerative cervical disc disease. There
      were 390 consecutive operations: 278 fused with autologous iliac crest bone graft
      and 112 with a PEEK (Polyetheretherketone) graft. RESULTS: No patient died.
      Thirty seven patients (9%) experienced one or more complications that could be
      related to the operation. These presented in the immediate, early and late
      periods in 17, 1 and 19 patients, respectively. Thus, 18/37 complications were
      detected before discharge from the neurosurgical department 48-72 h after
      operation and of these 17 (4.2%) were detected within the first 6 h after
      surgery. Each of the five potentially life-threatening neck hematomas was
      detected within 6 h (immediate). CONCLUSIONS: After anterior cervical discectomy
      and fusion, a 6 h postoperative observation period followed by discharge from the
      neurosurgical unit is likely to be as safe as observation as an inpatient for a
      longer period.

PMID- 18066486
TI  - Diversity of sulfate-reducing bacteria inhabiting the rhizosphere of Phragmites
      australis in Lake Velencei (Hungary) revealed by a combined cultivation-based and
      molecular approach.
AB  - The community structure of sulfate-reducing bacteria (SRB) associated with reed
      (Phragmites australis) rhizosphere in Lake Velencei (Hungary) was investigated by
      using cultivation-based and molecular methods. The cultivation methods were
      restricted to recover lactate-utilizing species with the exclusion of
      Desulfobacter and some Desulfobacterium species presumably not being dominant
      members of the examined community. The most-probable-number (MPN) estimations of
      lactate-utilizing SRB showed that the cell counts in reed rhizosphere were at
      least one order of magnitude higher than that in the bulk sediment. The number of
      endospores was low compared to the total SRB counts. From the highest positive
      dilution of MPN series, 47 strains were isolated and grouped by restriction
      fragment length polymorphism (RFLP) analysis of the amplified 16S ribosomal RNA
      (rRNA) and dsrAB (dissimilatory sulfite reductase) genes. Contrary to the
      physiological diversity of the isolates, the combined results of RFLP analysis
      revealed higher diversity at species as well as at subspecies level. Based on the
      partial 16S rRNA sequences, the representative strains were closely affiliated
      with the genera Desulfovibrio and Desulfotomaculum. The partial dsrAB sequences
      of the clones, recovered after isolation and PCR amplification of the community
      DNA, were related to hitherto uncultured species of the genera Desulfovibrio and
      Desulfobulbus. Nevertheless, the representative of the second largest clone group
      was shown to be closely affiliated with the sequenced dsrAB gene of a strain
      isolated from the same environment and identified as Desulfovibrio
      alcoholivorans. Another clone sequence was closely related to a possible novel
      species also isolated within the scope of this work.

PMID- 18066488
TI  - Radiographic features of tumefactive giant cavernous angiomas.
AB  - BACKGROUND: Giant cavernous angiomas (GCAs) are very rare, and imaging features
      of GCAs can be very different from those of typical cavernous angiomas (CAs),
      making them a diagnostic challenge. The purpose of the study was to evaluate the
      radiographic features of GCAs, with an emphasis on the differentiating features
      from neoplastic lesions. METHODS: The neuroradiological findings of 18 patients
      who harbored a histologically verified GCA (CA of 4 cm or larger) were reviewed
      retrospectively. The magnetic resonance imaging (MRI) appearance, enhancement
      pattern, presence of edema or mass effect, size, and location of each lesion were
      recorded. When available, pertinent clinical information, including age, sex, and
      mode of presentation, was obtained. FINDINGS: Seizures, neurologic deficits,
      hemorrhage, and hydrocephalus were the most common presenting symptoms. The
      lesions were hyperdense and nonenhancing on computed tomography with frequent
      calcifications. On MRI, the lesions most commonly had a multicystic appearance,
      representing blood of various ages, and multiple complete hemosiderin rings. GCAs
      can present in any location with associating edema and mass effect, giving them a
      tumefactive appearance. No developmental venous anomaly was observed with any
      lesion. CONCLUSIONS: Most GCAs in our series presented as multicystic lesions
      with complete hemosiderin rings on MRI, giving a "bubbles of blood" appearance.
      Although this characteristic feature is helpful in the diagnosis of many cases of
      GCAs, the correct diagnosis in the remaining cases may not be apparent until
      histopathological evaluation of the specimen is made.

PMID- 18066489
TI  - Is it safe to perform laparoscopic ventral hernia repair with mesh in elderly
      patients?
AB  - BACKGROUND: Ventral hernia is a common surgical condition occurring most often as
      a complication following abdominal surgery. Laparoscopic repair of a ventral
      hernia has been shown to be safe with low rates of complications, shortened
      length of stay, and low rates of early recurrence as compared to open surgery.
      Few studies have documented long-term outcomes of laparoscopic repair in elderly
      patients. The aim of this study is to report the long-term outcomes of
      laparoscopic ventral hernia repair with mesh in elderly patients. METHODS AND
      MATERIALS: This is a retrospective study in a university setting with IRB
      approval. Between the years 2000 and 2006, 117 patients underwent laparoscopic
      repair of ventral hernia with synthetic mesh. Data were collected using patient
      charts and radiographic reports. Patient variables included age, sex, size and
      content of hernia, size of mesh used, length of hospital stay (LHS), estimated
      blood loss (EBL), follow-up duration, and post-operative complications (PC)
      including infection, deep vein thrombosis, bleeding, and pulmonary embolism. The
      comparison was done between two different age groups (A <55 years old; B >or= 55
      years old). RESULTS: Current median (range) follow-up periods for group A (<55
      years) and B (>or=55 years) were 57.5 and 53 months, respectively. Group A (63
      patients) and B (54 patients) had same median LHS (1 day) and size of mesh
      utilized (285 cm(2)). For groups A and B, the percent female, and the percentages
      of recurrence, minimal EBL (<50 ml), and PC were 61.9 and 44.4; 1.6 and 3.7; 96.8
      and 92.6; 4.8 and 12.9, respectively. Median hernia sizes for groups A and B were
      55.1 and 54 cm(2). No significant differences were found for any of the above
      variables. CONCLUSION: No significant difference was found in outcomes between
      younger versus older patients undergoing laparoscopic ventral hernia repair with
      mesh. Laparoscopic repair provides a durable and effective method of repairing a
      ventral hernia with low morbidity and mortality in the elderly population.

PMID- 18066490
TI  - Association between four SNPs on chromosome 9p21 and myocardial infarction is
      replicated in an Italian population.
AB  - Genome-wide single nucleotide polymorphism (SNP) association studies recently
      identified four SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) on
      chromosome 9p21 that were associated with coronary artery disease (CAD) and
      myocardial infarction (MI) in Caucasian populations from northern Europe and
      North America. Our aim was to determine whether these SNPs were associated with
      MI in a southern Europe/Mediterranean population. We employed a case-control
      association design involving 416 MI patients and 308 non-MI controls from Italy.
      Significant allelic association was identified between all four SNPs and MI. The
      association remained significant after adjusting for covariates for MI (P=0.007
      0.029). One risk haplotype (GGGG; P=0.028) and one protective haplotype (AAAA;
      P=0.047) were identified. Genotypic association analysis demonstrated that the
      SNPs conferred susceptibility to MI most likely in a dominant model (P=0.0007
      0.013). When the case cohort was divided into a group of MI patients with a
      family history (n=248) and one group without it (n=168), the positive,
      significant association was identified only in the group with the family history.
      These results indicate that chromosome 9p21 confers risk for development of MI in
      an Italian population.

PMID- 18066491
TI  - Flavonoids in the leaves of Oxalis corniculata and sequestration of the
      flavonoids in the wing scales of the pale grass blue butterfly, Pseudozizeeria
      maha.
AB  - Three C-glycosylflavones in the leaves of Oxalis corniculata, the host plant of
      the lycaenid butterfly pale grass blue (Pseudozizeeria maha), were identified as
      6-C-glucosylluteolin (isoorientin), 6-C-glucosylapigenin (isovitexin) and
      isovitexin 7-methyl ether (swertisin). Comparative spectral and HPLC analyses
      between the leaf extract of the host plants and the wings of P. maha showed
      selective uptake of the host-plant flavonoid isovitexin to the wings of the
      butterfly.

PMID- 18066492
TI  - Is competition between mesocarp cells of peach fruits affected by the percentage
      of wild species genome?
AB  - The number of cells and the mean cell volume in the mesocarps of fruits from
      peach genotypes with different percentages of the genome of Prunus davidiana, a
      wild, related, species, were evaluated. The mesocarp mass varied greatly between
      the four groups of genotypes. The mean cell volume and the number of cells were
      negatively correlated within each group. This correlation can be interpreted as a
      relationship of competition between cells. In order to describe the type of
      competition in the different groups, we tried to adjust a model of competition
      for resources proposed by Lescourret and Genard (Ecoscience 10:334-341, 2003). To
      estimate the values of the three parameters of the model for the different
      groups, we applied model selection. Within nested models, we identified a single
      best model with six parameter values. This model was roughly accurate, but it
      allowed us to describe the general relationship for each group. The parameter
      values revealed a strong and under-compensating density-dependence effect for all
      groups. The percentage of P. davidiana genome appeared to influence the maximal
      number of cells and the strength of the competition, but no effect was found on
      the maximal mean volume of cells.

PMID- 18066493
TI  - Critical voltages and blocking stresses in nematic gels : dynamics of director
      rotation for nematic elastomers under electro-mechanical loads.
AB  - We present a model of the dynamics of director rotation in nematic gels under
      combined electro-mechanical loading. Focusing on a model specimen, we describe
      the critical voltages that must be exceeded to achieve director reorientation,
      and the blocking stresses that prevent alignment of the nematic director with the
      applied electric field. The corresponding phase diagram shows that the dynamic
      thresholds defined above are different from those predicted on the sole basis of
      energetics. Multistep loading programs are used to explore the energy landscape
      of our model specimen, showing the existence of multiple local minima under the
      same voltage and applied stress. This leads us to conclude that hysteresis should
      be expected in the electro-mechanical response of nematic gels.

PMID- 18066494
TI  - Cofactor-induced and mutational activity enhancement of coagulation factor VIIa.
AB  - Coagulation factor VIIa (FVIIa) is an atypical member of the trypsin family of
      serine proteases. It fails to attain spontaneously its catalytically competent
      conformation and requires its protein cofactor tissue factor (TF) to accomplish
      this. Over a number of years, this unique behaviour of FVIIa has prompted
      investigations of the TF-induced activation mechanism and the zymogenicity
      determinants in factor VIIa. Factor VIIa has gained additional interest in the
      past decade because of its development into a clinically useful haemostatic
      agent. Here, we present an overview of the current knowledge about the TF-induced
      allosteric activation of FVIIa and the various molecular approaches to enhance
      the intrinsic activity and efficacy of FVIIa.

PMID- 18066495
TI  - Serglycin--structure and biology.
AB  - Serglycin is a proteoglycan found in hematopoietic cells and endothelial cells.
      It has important functions related to formation of several types of storage
      granules. In connective tissue mast cells the covalently attached
      glycosaminoglycan is heparin, whereas mucosal mast cells and activated
      macrophages contain oversulfated chondroitin sulfate (type E). In mast cells,
      serglycin interact with histamine, chymase, tryptase and carboxypeptidase, in
      neutrophils with elastase, in cytotoxic T cells with granzyme B, in endothelial
      cells with tissue-type plasminogen activator and in macrophages with tumor
      necrosis factor-alpha. Serglycin is important for the retention of key
      inflammatory mediators inside storage granules and secretory vesicles. Serglycin
      can further modulate the activities of partner molecules in different ways after
      secretion from activated immune cells, through protection, transport, activation
      and interactions with substrates or target cells. Serglycin is a proteoglycan
      with important roles in inflammatory reactions.

PMID- 18066496
TI  - Plasticins: membrane-damaging peptides with 'chameleon-like' properties.
AB  - Plasticins belong to the dermaseptin superfamily of gene-encoded, membrane-active
      host defense peptides produced by the skin of hylid frogs. The plasticins, which
      are rich in Gly and Leu residues arranged in regular 5-mer motifs GXXXG (where X
      is any amino acid residue), have very similar amino acid sequences,
      hydrophobicities, and amphipathicities but differ markedly in their net charge,
      conformational plasticity, and activity spectra. The intrinsic flexibility and
      structural malleability of plasticins modulate their ability to bind to and
      disrupt the membranes of prokaryotic and eukaryotic cells, and/or to reach
      intracellular targets, therefore triggering functional versatility. This family
      of closely related but functionally divergent peptides constitutes a good model
      to address the relationships between structural polymorphism, membrane
      interacting properties, and the biological activity of antimicrobial, cell
      penetrating, and viral fusion peptides. Plasticins could thus serve as templates
      to design potent multifunctional drugs that could act simultaneously against
      bacterial pathogens and viruses.

PMID- 18066497
TI  - Meningiomas exhibit loss of heterozygosity of the APC gene.
AB  - The molecular mechanisms and candidate genes involved in development of
      meningiomas still need investigation and elucidation. In the present study 33
      meningiomas were analyzed regarding genetic changes of tumor suppressor gene
      Adenomatous polyposis coli (APC), a component of the wnt signaling. Gene
      instability was tested by polymerase chain reaction/loss of heterozygosity (LOH)
      using Restriction Fragment Length Polymorphism (RFLP) method. RFLP was performed
      by two genetic markers, Rsa I in APC's exon 11 and Msp I in its exon 15. The
      results of our analysis showed altogether 15 samples with LOH of the APC gene out
      of 32 heterozygous patients (47%). Seven patients had LOHs at both exons, while
      four LOHs were exclusive for exon 11 and four for exon 15. The changes were
      distributed according to pathohistological grade as follows: 46% of
      meningothelial meningioma showed LOH; 33% of fibrous; 75% of mixed
      (transitional); 75% of angiomatous, and one LOH was found in a single case of
      psammomatous meningioma. None of the LOHs were found in atypical and anaplastic
      cases. Immunostaining showed that samples with LOHs were accompanied with the
      absence of APC protein expression or presence of mutant APC proteins (chi(2 )=
      13.81, df = 2, P < 0.001). We also showed that nuclear localization of beta
      catenin correlates to APC genetic changes (chi(2 )= 21.96, df = 2, P < 0.0001).
      The results of this investigation suggest that genetic changes of APC gene play a
      role in meningioma formation.

PMID- 18066498
TI  - Cellulase elicitor induced accumulation of capsidiol in Capsicum annumm L.
      suspension cultures.
AB  - When growth-phase cell suspension cultures of Capsicum annuum were treated with
      cellulase-elicitor preparation at 3 microg/ml, the level of capsidiol was
      transiently increased in the culture media rather than in the cells reaching its
      maximum approx 24 h after treatment. With methyl jasmonate it took 18 h. Elicitor
      treatment doubled phospholiphase A(2) (PLA(2)) activity but simultaneous
      treatment with aristolochic acid, a PLA(2) inhibitor, inhibited sesquiterpenoid
      accumulation as well as PLA(2) activity. Mastoparan, a G protein activator,
      treatment also increased PLA(2) activity and capsidiol production. Taken
      together, the present study shows that induction of capsidiol production in the
      C. annuum is mediated by PLA(2) activation.

PMID- 18066499
TI  - Genetic transformation of barley microspores using anther bombardment.
AB  - Bombardment of intact anthers of commercial barley (Hordeum vulgare) varieties
      resulted in 0.5-1.0% of transformed microspores of which 20-40% continued in
      androgenic development (0.2% of all bombarded microspores). Using a system based
      on bombardment of anthers is therefore likely to be more technically efficient
      than the use of a microspore isolation, transformation and regeneration system.
      Bombardment of anthers has a number of technical and scientific advantages over
      existing systems for gene transfer and can be considered as a alternative method
      to existing methods for genetic transformation in barley.

PMID- 18066500
TI  - A novel assay system for the measurement of transketolase activity using
      xylulokinase from Saccharomyces cerevisiae.
AB  - The conventional method of transketolase (TKT) activity assay uses ribose 5
      phosphate and xylulose 5-phosphate as substrates. However, a new method of TKT
      assay is currently required since xylulose 5-phosphate is no longer commercially
      available and is difficult to synthesize chemically. Although there are effective
      assays for TKT using non-natural substrates, these are inadequate for evaluating
      changes in enzyme activity and affinity toward real substrates. As a solution to
      such problems, we describe a novel assay system using xylulokinase (XK) from
      Saccharomyces cerevisiae. As for this purpose, the XK was overexpressed in E.
      coli, separated and purified in a single step, added to induce a reaction that
      generated xylulose 5-phosphate, which was integrated into the conventional TKT
      assay. The new coupling assay gave reproducible results with E. coli TKT and had
      a detection limit up to 5 x 10(-4)unit/mg protein. A reliable result was also
      achieved for the incorporation of XK and TKT into a single reaction.

PMID- 18066501
TI  - Refolding of denatured lysozyme by water-in-oil microemulsions of sucrose fatty
      acid esters.
AB  - Water-in-oil (w/o) microemulsion of sucrose fatty acid ester was used to renature
      denatured hen egg white lysozyme without aggregation. After lysozyme was
      denatured in 5 M guanidine hydrochloride for 24 h, the resultant denatured
      lysozyme was held in the microemulsion, overnight at 25 degrees C. Renatured
      lysozyme was transferred from the microemulsion phase to the recovery aqueous
      phase by conventional liquid-liquid extraction. The enzymatic activity of the
      recovered lysozyme was 93%.

PMID- 18066502
TI  - Temperature rhythm in aneurysmal subarachnoid hemorrhage.
AB  - INTRODUCTION: In the acute phase following brain injury, alterations in
      temperature regulation occur commonly and are associated with poorer outcome.
      However, few studies have examined temperature rhythm following brain insult,
      such as rupture and surgical management of ruptured cerebral aneurysms, and its
      association with clinical factors and outcome. METHODS: This study describes
      diurnal temperature patterns in patients hospitalized for acute management of
      cerebral aneurysms (n = 86). Temperature mesor, amplitude, and acrophase were
      estimated from recorded temperature measurements using cosinor analysis. The
      association of these patterns with clinical condition, mortality, and 6-month
      functional outcome was examined. RESULTS: Changes in the temperature cosinor
      parameters were varied and individual. Most patients experienced elevated mesors
      (Mean +/- SD, 37.8 +/- 0.4 degrees C) and blunted amplitudes (0.27 +/- 0.14
      degrees C). Acrophases were widely dispersed, with only 27% in the normative 12
      noon to 6 PM quadrant. Cosinor parameters (particularly the mesor) showed greater
      alteration in patients with worse initial condition (e.g. Hunt and Hess score >
      or = 2: P = 0.001, Glasgow Coma Scale < 15: P = 0.001) and poorer 6-month outcome
      (e.g. mortality: P = 0.013, Extended Glasgow Outcome Scale < 5: P = 0.018).
      CONCLUSION: Abnormal cosinor parameters provided additional predictive
      information in relation to outcome, beyond the impact of initial neurologic
      condition. Further research is needed to understand the pathophysiology of
      temperature regulation following cerebral aneurysm rupture and to determine if
      temperature management strategies can alter outcome.

PMID- 18066504
TI  - Angiosarcomas and taxanes.
AB  - Angiosarcomas (AS) are a heterogeneous group of rare and aggressive malignancies.
      The best treatment of localized AS includes wide resection following by adjuvant
      radiation therapy as possible. The current standard treatment of metastatic AS
      remains a doxorubicin-based regimen. This treatment provides a median progression
      free survival and a median overall survival of about 4 and 8 months,
      respectively. Numerous case reports and retrospective studies have suggested that
      taxanes (paclitaxel or docetaxel) may provide some objective responses. The
      French Sarcoma Group has conducted a phase II clinical trial, which states the
      benefit of weekly paclitaxel in patients with unresectable or metastatic AS.
      After 2 cycles, the non-progression rate was 78% and complete histological
      responses were observed in 3 out of 30 cases. Further clinical studies are needed
      to confirm clinic impact of weekly paclitaxel on survival and to assess the role
      of taxanes in the multidisciplinary treatment of AS.

PMID- 18066505
TI  - Challenges in the diagnosis and management of musculoskeletal tumours in Nigeria.
AB  - The management of musculoskeletal tumours is important because of the high
      mortality rates associated with the available treatment modalities. A 5-year
      prospective study of bone and soft-tissue tumours is presented, along with the
      difficulties encountered in diagnosis and treatment. There were 71 patients
      (male:female ratio of 1.7:1, age range 5-85 years, mean age 32 years) with an
      average duration of 24.7 weeks (range 1 day to 34 years) before presentation. No
      patient had computed tomography (CT) scanning or magnetic resonance imaging (MRI)
      due to financial constraints, 95% had biopsies and X-rays, 15% could afford
      chemotherapy/ror chemotherapy is a sad consequence. 50% agreed to amputation. In
      the soft-tissue sarcoma group, only one of three patients could pay for limb
      sparing surgery. In the benign group, 65% had limb-sparing surgeries and 15% had
      amputation. Fifty percent (50%) of patients were lost to follow up within 3
      months and 39% of the malignant group died within the same period.
      Musculoskeletal tumours are a reality in our environment and a significant
      portion of our population have financial limitations. Ignorance and cultural
      beliefs promote late presentation to our hospitals, which are poorly equipped to
      give optimal care, despite the presence of trained personnel.

PMID- 18066506
TI  - Structure of Photosystems I and II.
AB  - Photosynthesis is the major process that converts solar energy into chemical
      energy on Earth. Two and a half billion years ago, the ancestors of cyanobacteria
      were able to use water as electron source for the photosynthetic process, thereby
      evolving oxygen and changing the atmosphere of our planet Earth. Two large
      membrane protein complexes, Photosystems I and II, catalyze the primary step in
      this energy conversion, the light-induced charge separation across the
      photosynthetic membrane. This chapter describes and compares the structure of two
      Photosystems and discusses their function in respect to the mechanism of light
      harvesting, electron transfer and water splitting.

PMID- 18066507
TI  - [Metabolic alkalosis despite hyperlactatemia and hypercapnia. Interpretation and
      therapy with help of the Stewart concept].
AB  - Acid-base disturbances are commonly found in critically ill patients and are
      often associated with fatal complications. The basis of a successful treatment is
      a thorough understanding of the causes of these disorders. The "classical
      methods" to explain acid-base disorders--pH, base excess and bicarbonate
      concentration--mostly do not provide a causal correlation to the underlying
      pathology. An unusual case of a combined respiratory-metabolic disorder with
      hyperlactatemia and hypercapnia is presented. An acidosis masked by hypochloremic
      and hypoalbuminemic alkalosis was identified with the help of Stewart's concept
      and finally permitted a successful therapy. The modern Stewart concept provides
      enhanced information, enabling an exact diagnosis and causal therapy even in
      complex cases.

PMID- 18066508
TI  - [Therapy of mediastinitis in patients with esophageal cancer].
AB  - Mediastinitis caused by anastomotic leaks is the most severe complication after
      esophagectomy and the major source of morbidity and mortality. It is
      characterized by local intrathoracic reactions (mediastinitis) and systemic
      extrathoracic reactions (sepsis). Consequently the therapeutic concepts are
      clearly defined. To achieve successful management, early diagnostic work-up is
      mandatory in every disturbance of the normal postoperative course. This includes
      direct endoscopic inspection of the anastomosis to evaluate the vitality of the
      anastomosed organs and the size of the leak. According to location and clinical
      classifications of the leak, the spectrum of therapeutic options ranges from
      simple drainage procedures, endoscopic interventions, and stent implantation to
      reoperation or discontinuity resection. In any case the treatment goals must be
      immediate and sufficient drainage of the leakage and hindrance of further
      contamination across the leakage by gastrointestinal content. Also mandatory is
      the early initiation of supportive systemic strategies according to
      pathophysiologic principles of sepsis. The fundamental requirements for
      successful management are therefore aggressive local intervention and application
      of new concepts in sepsis therapy.

PMID- 18066509
TI  - [Blister-forming mucous membrane disease with cicatricial laryngeal stenosis].

PMID- 18066503
TI  - Molecular mechanisms of apoptosis in cerebral ischemia: multiple neuroprotective
      opportunities.
AB  - Cerebral ischemia/reperfusion (I/R) injury triggers multiple and distinct but
      overlapping cell signaling pathways, which may lead to cell survival or cell
      damage. There is overwhelming evidence to suggest that besides necrosis,
      apoptosis do contributes significantly to the cell death subsequent to I/R
      injury. Both extrinsic and intrinsic apoptotic pathways play a vital role, and
      upon initiation, these pathways recruit downstream apoptotic molecules to execute
      cell death. Caspases and Bcl-2 family members appear to be crucial in regulating
      multiple apoptotic cell death pathways initiated during I/R. Similarly, inhibitor
      of apoptosis family of proteins (IAPs), mitogen-activated protein kinases, and
      newly identified apoptogenic molecules, like second mitochondrial-activated
      factor/direct IAP-binding protein with low pI (Smac/Diablo), omi/high-temperature
      requirement serine protease A2 (Omi/HtrA2), X-linked mammalian inhibitor of
      apoptosis protein-associated factor 1, and apoptosis-inducing factor, have
      emerged as potent regulators of cellular apoptotic/antiapoptotic machinery. All
      instances of cell survival/death mechanisms triggered during I/R are multifaceted
      and interlinked, which ultimately decide the fate of brain cells. Moreover,
      apoptotic cross-talk between major subcellular organelles suggests that
      therapeutic strategies should be optimally directed at multiple
      targets/mechanisms for better therapeutic outcome. Based on the current
      knowledge, this review briefly focuses I/R injury-induced multiple mechanisms of
      apoptosis, involving key apoptotic regulators and their emerging roles in
      orchestrating cell death programme. In addition, we have also highlighted the
      role of autophagy in modulating cell survival/death during cerebral ischemia.
      Furthermore, an attempt has been made to provide an encouraging outlook on
      emerging therapeutic approaches for cerebral ischemia.

PMID- 18066511
TI  - [Parotid mass with minimal clinical signs and symptoms].

PMID- 18066510
TI  - [Primary B-cell non-Hodgkin lymphoma of the internal auditory canal: case report
      and literature review].
AB  - A primary non-Hodgkin lymphoma (NHL) of the internal auditory canal or the
      cerebellopontine angle is an absolute rarity, even among the unusual lesions
      encountered there. Schwannomas or meningiomas account for approximately 90-95% of
      the tumors of the cerebellopontine angle and the internal auditory canal.
      Atypical symptoms, such as facial nerve palsy or rapid progression, require
      differential diagnostics to identify less frequent entities. However, clinical
      symptoms or the image morphology cannot confirm the diagnosis of a lymphoma. If a
      malignant process is suspected during surgical exploration, an immediate
      intraoperative biopsy can give important clues for appropriate treatment. The
      course, diagnostics, and therapy of a rare case of primary B-cell NHL of the
      internal auditory canal are reported here.

PMID- 18066512
TI  - [Some thoughts on the therapy of hearing disturbances in the future].

PMID- 18066513
TI  - [Group therapeutic concept for chronic tinnitus].
AB  - The aim of this article is to show an established group therapeutic concept for
      chronic tinnitus. The treatment of chronic tinnitus is intended to improve the
      way patients cope with tinnitus but it does not eliminate it. It means that
      patients learn how to reduce the impairment they are experiencing. Patients with
      tinnitus are supported in the process of habituation through the treatment.
      Multimodal cognitive behavioral therapeutic interventions in a group setting are
      particularly helpful because they may demonstrate differences in the influence of
      cognitive processes on the emotional perception of the tinnitus between the
      patients. Psychological factors like emotional support through other patients and
      learning from other examples can ease the process of internalizing coping
      strategies. Psychological processes seem to be of particular importance. Those
      processes can have an effect on concentration, appraisal, and coping with the
      tinnitus. Progressive muscle relaxation using Jacobson's technique, physical
      therapy, education via lectures, training of selective attention and change of
      appraisal, mental attitude and behavior concerning the tinnitus are the main
      factors in tinnitus therapy and can enable tinnitus patients to decrease their
      psychological strain.

PMID- 18066514
TI  - [Primary malignant melanoma of the parotid gland: a case report and review of the
      literature].
AB  - Malignant melanomas (MMs) of the parotid gland are relatively uncommon. They
      occur almost invariably as metastases from a primary tumour located in the region
      of the scalp or the mucous membranes of the nose, paranasal sinuses, or throat.
      Primary MMs arising in the parotid gland are extremely rare. It is assumed that
      they originate in the glandular tissue or in intraglandular lymph nodes. We
      present a case report and review of the literature on the diagnosis, treatment,
      and prognosis of intraparotid malignant melanoma. Diagnosis is based primarily on
      B-scan ultrasonography and fine-needle aspiration cytology. Patients with a
      cytological diagnosis of MM are further evaluated by magnetic resonance imaging
      and positron emission tomography and receive a thorough ear-nose-throat and
      dermatological examination. The treatment of choice is total parotidectomy and
      selective neck dissection. The effectiveness of adjuvant treatments such as
      radiotherapy, chemotherapy, or immunotherapy remains controversial. Patients with
      primary MMs of the parotid gland appear to have a better prognosis than those
      with parotid metastases from melanomas of the skin or mucous membranes.

PMID- 18066515
TI  - [A new locus for an autosomal dominant, non-syndromic hearing impairment (DFNA57)
      located on chromosome 19p13.2 and overlapping with DFNB15].
AB  - BACKGROUND: Non-syndromic hearing loss is the most genetically heterogeneous
      trait known in humans. To date, 54 loci for autosomal dominant non-syndromic
      sensorineural hearing loss (NSSHL) have been identified by linkage analysis.
      METHODS: In this study a German pedigree has been identified segregating a
      progressive bilateral loss of lower and middle frequencies. RESULTS: A genome
      wide screening and linkage analysis revealed the existence of a new NSSHL locus
      (DFNA57). The phenotype was mapped to a 10 degrees Mbp interval on chromosome
      19p13.2 from 7.8 to 18.2 degrees Mbp, a maximum 2-point LOD score of 3.08 was
      obtained for the marker D19S586. The region overlaps with the recessive locus
      DFNB15. CONCLUSION: The results underline the heterogeneity of hereditary hearing
      disorders. Identification of genes can help to reach a better understanding of
      the molecular mechanism of hearing.

PMID- 18066516
TI  - [Diving fitness of children and adolescents. Importance for ENT doctors].
AB  - About 10% of all sport scuba divers are children and adolescents. Little is known
      about the particular risks and consequences of this sport on a child's health.
      Due to the peculiarities of childhood anatomy and physiology, certain
      restrictions apply to the diving fitness of children and adolescents. Before
      starting scuba training, the presence of particular cognitive abilities must be
      demonstrated and eustachian tube dysfunction must be ruled out by a specialist.
      Medical contra-indications to scuba diving for adults apply to children too but
      must be adapted. Relative risks for adults may translate to absolute contra
      indications in children and adolescents. When planning dives, there should be
      rigorous limitations as to depth and time. Experienced adult divers must always
      assist with dive planning and accompany children and adolescents when scuba
      diving.

PMID- 18066517
TI  - [Emergency room management of contaminated patients].
AB  - Accidents with the risk of exposure to hazardous nuclear, biological, or chemical
      materials are rare. Most emergency rooms are not familiar with the management of
      contaminated patients after this kind of incident. There are also ambiguous cases
      concerning the contamination status of the patient. The medical attendance should
      be performed carefully and under special security arrangements until a hazard for
      third persons can be excluded. The security arrangements should protect both
      (medical) personnel and third persons. Early medical treatment combined with
      decontamination should be the aim. Based on the case of a contaminated patient
      who was brought to our emergency department after an explosion of a fog grenade
      with red phosphorus, we discuss our management concept and the current
      literature.

PMID- 18066518
TI  - [Pseudoarthrosis of anterior pelvic ring fracture].
AB  - It is rare for there to be healing problems after anterior pelvic fractures. An
      internet search produced only a small number of hits. This paper recounts the
      course in two patients who experienced symptomatic nonunion of anterior pelvic
      fractures after stable osteosynthesis with locking plates. Stable internal
      fixation with locking plates eventually led to successful healing after both
      nonunion of the ischial ramus and nonunion of the transitional zone between the
      inferior pubic ramus and the ischial ramus, and also of nonunion of the superior
      pubic ramus, in both patients. The study demonstrates that it is possible to
      stabilise nonunion of the superior pubic ramus by internal fixation of the
      ischial ramus and of the transitional zone between the inferior pubic ramus and
      the ischial ramus with locking plates.

PMID- 18066519
TI  - [Elastic stable intramedullary nailing as alternative therapy for pediatric
      Monteggia fractures].
AB  - Forearm fractures are some of the most common injuries in childhood. Monteggia
      fractures and Monteggia equivalents are rare injuries of the proximal forearm,
      but they are important because of their special biomechanics. Many authors have
      reported good results with excellent function if the Monteggia injuries are
      diagnosed primarily and treated by an axial reposition of the ulna and by an
      exactly repositioned proximal radioulnar joint. In our investigation, some
      clinical cases of pediatric Monteggia fractures were operated upon using the
      technique of elastic stable intramedullary nailing (ESIN). In correct
      indications, ESIN could be used as a minimally invasive therapeutic alternative
      to plate osteosynthesis for treating pediatric Monteggia injuries.

PMID- 18066520
TI  - [Somatoform disorders. Clinical evidence, etiology, pathogenesis, and therapy].
AB  - Patients presenting with bodily symptoms and complaints that are not explained by
      organic pathology or well-known pathophysiological mechanisms comprise a major
      challenge to any medical care system. From a perspective of psychiatric
      classification, such medically unexplained somatic symptoms are diagnosed as
      depressive and anxiety disorders on the one hand or somatoform disorders on the
      other. In clinical physical medicine a quite different diagnostic approach is
      taken to conceptualize functional somatic syndromes. Concepts of somatoform
      disorders are outlined, critical issues regarding existing diagnostic systems are
      discussed, and possible alternative approaches for upcoming versions of DSM-V and
      ICD-11 are mentioned. The main somatoform disorders are described in their
      clinical characteristics. Etiopathogenetically, somatoform disorders may best be
      considered within a multifactorial model. Some pragmatic guidelines for
      multimodal treatment of somatoform disorders are outlined.

PMID- 18066521
TI  - Inhibition of c-jun N terminal kinase (JNK) improves functional beta cell mass in
      human islets and leads to AKT and glycogen synthase kinase-3 (GSK-3)
      phosphorylation.
AB  - AIMS/HYPOTHESIS: Activation of c-jun N-terminal kinase (JNK) has been described
      in islet isolation and engraftment, making JNK a key target in islet
      transplantation. The objective of this study was to investigate if JNK inhibition
      with a cell-permeable TAT peptide inhibitor (L-JNKI) protects functional beta
      cell mass in human islets and affects AKT and its substrates in islet cells.
      METHODS: The effect of L-JNKI (10 micromol/l) on islet count, mitochondrial
      membrane potential, glucose-stimulated insulin release and phosphorylation of
      both AKT and its substrates, as well as on reversal of diabetes in
      immunodeficient diabetic Nu/Nu mice was studied. RESULTS: In vitro, L-JNKI
      reduced the islet loss in culture and protected from cell death caused by acute
      cytokine exposure. In vivo, treatment of freshly isolated human islets and
      diabetic Nu/Nu mice recipients of such islets resulted in improved functional
      beta cell mass. We showed that L-JNKI activates AKT and downregulates glycogen
      synthase kinase-3 beta (GSK-3B) in human islets exposed to cytokines, while other
      AKT substrates were unaffected, suggesting that a specific AKT/GSK-3B regulation
      by L-JNKI may represent one of its mechanisms of cytoprotection.
      CONCLUSIONS/INTERPRETATION: In conclusion, we have demonstrated that targeting
      JNK in human pancreatic islets results in improved functional beta cell mass and
      in the regulation of AKT/GSK3B activity.

PMID- 18066522
TI  - Systematic surveillance cultures as a tool to predict involvement of multidrug
      antibiotic resistant bacteria in ventilator-associated pneumonia.
AB  - OBJECTIVE: To assess prediction of multidrug resistant (MDR) pathogens in
      ventilator-associated pneumonia (VAP) by systematic surveillance cultures (SC)
      and to assess the contribution of SC to initial antibiotic therapy. DESIGN:
      Prospective cohort study of patients with microbiologically confirmed VAP.
      Comparison of actual early antibiotic coverage with three hypothetical empirical
      schemes. SETTING: A 50-bed university hospital ICU. SC consisted of oral, nasal,
      urinary and rectal samples upon admission, 3-weekly urinary and 1-weekly oral,
      nasal, and rectal samples in all patients, 3-weekly tracheal aspirates in
      intubated patients. RESULTS: MDR pathogens were found in 86 of 199 VAP episodes.
      Sensitivity of SC to predict MDR pathogens was 69% (tracheal SC) and 82% (all
      SC); specificity was 96% (tracheal) and 91% (all), respectively. Appropriate
      antibiotic coverage within 24 h and 48 h following MDR VAP was 77% and 89%,
      respectively. A carbapenem-based empirical scheme would have been equally
      appropriate (83% vs. 77% at 24 h; 83% vs. 89% at 48 h), but a beta-lactam
      fluoroquinolone empirical therapy would have been less (59% vs. 77% at 24 h; 59%
      vs. 89% at 48 h) as would have been beta-lactam-aminoglycoside therapy (68% vs.
      77% at 24 h; 68% vs. 89% at 48 h). Empirical comparators would have resulted in
      significantly more prescription of broad-spectrum antibiotics within the first 48
      h. CONCLUSIONS: With MDR pathogens highly prevalent, systematic SC predicted MDR
      pathogens causing VAP in 69% to 82% and may have contributed to high rates of
      early appropriate antibiotic therapy with limited use of broad-spectrum
      antimicrobials.

PMID- 18066523
TI  - Refractory intracranial hypertension and "second-tier" therapies in traumatic
      brain injury.
AB  - OBJECTIVE: To quantify the occurrence of high intracranial pressure (HICP)
      refractory to conventional medical therapy after traumatic brain injury (TBI) and
      to describe the use of more aggressive therapies (profound hyperventilation,
      barbiturates, decompressive craniectomy). DESIGN: Prospective study of 407
      consecutive TBI patients SETTING: Three neurosurgical intensive care units (ICU).
      MEASUREMENTS AND RESULTS: Intracranial pressure (ICP) was studied during the
      first week after TBI; 153 patients had at least 1 day of ICP>20 mmHg. Early
      surgery was necessary for 221 cases, and standard medical therapy [sedation,
      mannitol, cerebrospinal fluid (CSF) withdrawal, PaCO2 30-35 mmHg] was used in 135
      patients. Reinforced treatment (PaCO2 25-29 mmHg, induced arterial hypertension,
      muscle relaxants) was used in 179 cases (44%), and second-tier therapies in 80
      (20%). Surgical decompression and/or barbiturates were used in 28 of 407 cases
      (7%). Six-month outcome was recorded in 367 cases using the Glasgow outcome scale
      (GOS). The outcome was favorable (good recovery or moderate disability) in 195
      cases (53%) and unfavorable (all the other categories) in 172 (47%). HICP was
      associated with worse outcome. Outcome for cases who had received second-tier
      therapies was significantly worse (43% favorable at 6 months, p=0.03).
      CONCLUSIONS: HICP is frequent and is associated with worse outcome. ICP was
      controlled by early surgery and first-tier therapies in the majority of cases.
      Profound hyperventilation, surgical decompression and barbiturates were used in
      various combinations in a minority of cases. The indications for surgical
      decompression and/or barbiturates seem restricted to less than 10% of severe TBI.

PMID- 18066525
TI  - Freezing causes changes in the meniscus collagen net: a new ultrastructural
      meniscus disarray scale.
AB  - Alterations in meniscal permeability leading to nutritional deficit have been
      suggested as a cause of shrinkage in meniscal transplantation. The purpose of
      this study was to ascertain how freezing, one of the most common procedures used
      to preserve meniscal allografts, alters the collagen's architecture. Twenty-six
      fresh human external menisci were analyzed with transmission electron microscopy.
      Thirteen of them were previously frozen at -80 degrees C while the rest were used
      as controls. A new scale of the collagen meniscal architecture was proposed
      according to the collagen's periodicity and degree of disruption, loss of
      banding, degree of collagen packing, fibril size variability and its
      intrafibrilar oedema. Each meniscus was scored from 0 to 7. Subsequently they
      were classified in grades ranging from a normal state (grade I; 0-2 points) to
      severe disarray (grade III; 5-7 points). The fibril collagen diameters of those
      menisci which had been previously frozen showed an average size in the
      longitudinal section of 14.26 nm, whereas it was 17.28 nm in the menisci used as
      controls (p=0.019). In the transverse section, the frozen menisci averaged 13.14
      and 16.93 nm in the controls (p=0.003). Samples of the 13 previously frozen
      menisci were classified as grade III in 61.54% of the cases. In the control
      group, all the menisci were classified either as grade I or II. The frozen
      menisci averaged 4.85 points, whereas the control group did so at 2.46 (p<0.001).
      The fibril diameters in frozen menisci showed a thinner diameter and had a higher
      degree of disarray. Therefore, the results suggest that the freezing process
      alters the menisci's collagen net. This could partially explain the pathological
      changes found in shrunken menisci after transplantation.

PMID- 18066524
TI  - Vasopressin vs. terlipressin in the treatment of cardiovascular failure in
      sepsis.
AB  - BACKGROUND: Arginine vasopressin (AVP) and terlipressin (TP) are increasingly
      used as adjunct vasopressors in the treatment of septic shock. Despite important
      pharmacological differences between the two drugs (e.g., receptor selectivity,
      effective half-life) the use of either substance is determined mainly by local
      availability and institutional inventory. We briefly describe the pathophysiology
      and pharmacology of septic shock relevant to the treatment with vasopressin
      analogues. In addition, differences in pharmacokinetics and pharmacodynamics
      between AVP and TP are discussed. DISCUSSION: The current literature suggests
      that neither AVP nor TP should be administered in high doses in patients with
      septic shock. Furthermore, increasing evidence indicates that early
      administration of vasopressin analogues may improve outcome as compared to a last
      resort treatment. Low-dose infusion of AVP (0.6-2.4 U/h) has been demonstrated to
      be a safe adjunct in the management of septic shock. The V2 agonistic effects of
      AVP may exert favorable effects on hepatosplanchnic, renal, pulmonary, and
      coronary perfusion. However, the higher V1 receptor selectivity of TP may prove
      more potent in restoring arterial blood pressure and avoiding rebound
      hypotension, while carrying the risk of sustained global and regional
      vasoconstriction after bolus injection. CONCLUSIONS: Evidence from experimental
      studies and initial clinical reports suggests that continuous low-dose infusion
      of TP may stabilize hemodynamics in septic shock with reduced side effects.
      However, randomized, controlled trials are necessary to determine the role of
      bolus or continuous infusion of TP in the treatment of septic shock before this
      approach can be recommended for routine clinical use.

PMID- 18066526
TI  - Assessment of the "functional length" of the three bundles of the anterior
      cruciate ligament.
AB  - The objectives of the present study are to compare "functional length" between
      the three bundles of the anterior cruciate ligament (ACL) from extension to deep
      flexion and to perform a sensitivity study on the patterns of "functional length"
      change due to deviations in insertion site selection. Nine knees of healthy
      volunteers were examined using a horizontal open magnetic resonance apparatus
      with the knee at 0 degrees -150 degrees of flexion and created three-dimensional
      (3D) virtual models of the knee. The femoral and tibial attachment sites of the
      three ACL bundles were determined, and the distance between the attachment sites
      was automatically calculated as the "functional length" of each bundle in each
      position. After changing the attachment sites, computer simulation was performed
      to investigate in vivo "functional length" changes for the three bundles of the
      ACL in normal knee kinematics from extension to deep flexion. Three bundles
      statistically significantly changed in "functional length" during
      flexion/extension, while they were longest at full extension, and decreased with
      increasing knee flexion to 100 degrees . They were smallest at flexion of 100
      degrees , with increase lengths with flexion deeper than 100 degrees . Deviation
      of 6 mm of insertion site beyond attachment area caused significant alteration in
      the pattern of "functional length" change of each bundle, while deviation of 3 mm
      within attachment area caused no significant difference. The "functional length"
      of the three ACL bundles was not isometric, not even the antero-medial bundle.
      The "functional length" might be of major importance in terms of the site of the
      ACL insertion. The "functional length" of multiple bundles of the ACL and the
      pattern of their changes are useful for not only graft choice and preparation but
      also knee angle and initial tension at graft fixation during multiple-bundle ACL
      reconstruction surgery.

PMID- 18066527
TI  - The surgical outcome of immediate arthroscopic Bankart repair for first time
      anterior shoulder dislocation in young active patients.
AB  - This study evaluated the surgical outcomes of young active patients with
      arthroscopic Bankart repair within 1 month after first-time anterior shoulder
      dislocation. From July 2002-October 2004, patients presented with first-time
      traumatic anterior shoulder dislocation and treated with arthroscopic
      stabilization within 1 month of injury were retrospectively reviewed. Magnetic
      resonance imaging and computed tomography were performed before the operation in
      all cases. Cases with contralateral shoulder multidirectional instability or
      glenoid bone loss of more than 30% on preoperative computed tomography on the
      injury side were excluded. All patients were treated with arthroscopic Bankart
      repair, using metallic suture anchors or soft tissue bio-absorbable anchors by a
      same group of surgeons and followed the same rehabilitation protocol. Recurrence,
      instability signs, range of motion, WOSI score, Rowe score and complications were
      assessed. Thirty-eight patients were recruited: the average age was 21 (16-30).
      All patients had definite trauma history. Radiologically, all patients had
      Bankart/Hill-Sachs lesion. All the operations were done within 1 month after
      injury (6-25 days). The average hospital stay was 1.2 days (1-5 days). The
      average follow-up was 28 months (24-48 months). There were two cases of
      posttraumatic re-dislocation (5.2%). The average external rotation lag was 5
      degrees (0-15) in 90 degrees shoulder abduction when compared with contralateral
      side. 95% of patients had excellent or good Rowe score. The average WOSI score
      was 83%. There was one case of transient ulnar nerve palsy and one case of
      superficial wound infection. This study concluded that immediate arthroscopic
      Bankart repair with an accelerated rehabilitation program is an effective and
      safe technique for treating young active patients with first-time traumatic
      anterior shoulder dislocation.

PMID- 18066528
TI  - Tibial bone bridge and bone block fixation in double-bundle anterior cruciate
      ligament reconstruction without hardware: a technical note.
AB  - Current techniques for tibial graft fixation in four tunnels double bundle (DB)
      anterior cruciate ligament (ACL) reconstruction are by means of two interference
      screws or by extracortical fixation with a variety of different implants. We
      introduce a new alternative tibial graft fixation technique for four tunnels DB
      ACL reconstruction without hardware. About 3.5 to 5.5 cm bone cylinder with a
      diameter of 7 mm is harvested from the anteromedial (and posterolateral) tibial
      bone tunnel (s) with a core reamer. The anteromedial (AM) and posterolateral (PL)
      hamstring tendon grafts (or alternatively tendon allografts) are looped over an
      extracortical femoral fixation device and cut in length according to the total
      femorotibial bone tunnel length. The distal 3 cm of each, the AM- and PL bundle
      graft are armed with two strong No. 2 nonresorbable sutures and the four suture
      ends of each graft are tied to each other over the 2 cm wide cortical bone bridge
      between the tibial AM and PL bone tunnel. In addition the AM- and/or PL bone
      block which was harvested at the beginning of the procedure is re-impacted into
      the two tibial bone tunnels. A dorsal splint is used for the first two
      postoperative weeks and physiotherapy is started the second postoperative day.
      The technique is applicable for four tunnels DB ACL reconstruction in patients
      with good tibial bone quality. The strong fixation technique preserves important
      tibial bone stock and avoids the use of tibial hardware which knows
      disadvantages. It does increase tendon to bone contact and tendon-to-bone healing
      and does reduce implant costs to those of a single bundle (SB) ACL
      reconstruction. Revision surgery may be facilitated significantly but the
      technique should not be used when bony defects are present. In case of
      insufficient bone bridge fixation or bone blocks hardware fixation can be applied
      as usual.

PMID- 18066529
TI  - Arthroscopic double bundle ACL reconstruction using a bone patellar tendon bone
      gracilis tendon composite autograft: a technical note.
AB  - The authors devised an alternative arthroscopic double bundle ACL reconstruction
      technique using a bone patellar tendon bone (BPTB)-gracilis tendon composite
      autograft. One tibial and two femoral tunnels were used to reconstruct two
      bundles of anterior cruciate ligaments (ACL) [an anteromedial bundle (AM) and a
      post-erolateral bundle (PL)]. BTBB was fixed in the tunnels produced on the
      isometric points of the tibia and femur using the conventional technique. The
      gracilis tendon was then fixed in a PL tunnel produced using the outside-in
      technique. The authors consider that the devised technique based on a combination
      of autogenous bone patellar bone graft and gracilis tendon, can minimize tunnel
      widening post-operatively, allow easier revision should the reconstructed ACL
      fail, and also provides an alternative means of restoring rotation stability.

PMID- 18066530
TI  - Open versus percutaneous repair in the treatment of acute Achilles tendon
      rupture: a randomized prospective study.
AB  - There is no agreement on the ideal type of surgical management for Achilles
      tendon rupture. The present randomized prospective study was performed to compare
      outcome data of open and percutaneous repair in the treatment of Achilles tendon
      rupture. Forty consecutive patients with acute rupture of Achilles tendon were
      recruited. Patients were randomized to receive open (group A) or percutaneous
      repair with Tenolig (group B). All patients followed the same rehabilitation
      protocol except for slight differences in the duration of immobilization. Follow
      up included objective evaluation (at 4 and 12 months), subjective evaluation
      using the SF-12 questionnaire (at 24 months), and bilateral ultrasound scanning
      and isokinetic testing (at 12 months). The differences in the parameters
      evaluated clinically were not significant except for ankle circumference, which
      was significantly greater in group B. There were two minor complications in the
      open repair group and one case of failed repair in the percutaneous group. SF-12
      questionnaire, ultrasound and isokinetic test data did not show significant
      differences between the groups. The present study demonstrates that the open and
      the percutaneous technique are both safe and effective in repairing the ruptured
      Achilles tendon and that both afford the same degree of restoration of clinical,
      ultrasound and isokinetic patterns. Medium-term results were substantially
      comparable. Percutaneous repair is performed on a day-surgery basis, it reduces
      cutaneous complications and operation times, and enables faster recovery,
      enhancing overall patient compliance. To us, these characteristics make it
      preferable to open repair in managing subcutaneous ruptures of Achilles tendon in
      non-professional sports practicing adults.

PMID- 18066531
TI  - Quorum sensing by N-acylhomoserine lactones is not required for Aeromonas
      hydrophila during growth with organic particles in lake water microcosms.
AB  - It was investigated whether quorum sensing (QS) mediated by N-acylhomoserine
      lactones (AHLs) was important for heterotrophic bacteria from the littoral zone
      of the oligotrophic Lake Constance for growth with organic particles. More than
      900 colonies from lake water microcosms with artificial organic aggregates
      consisting of autoclaved unicellular algae embedded in agarose beads were
      screened for AHL-production. AHL-producing bacteria of the genus Aeromonas
      enriched in the microcosms but AHLs could not be detected in any microcosm. To
      test for a potential function of AHL-mediated QS, growth experiments with the
      wild type and an AHL-deficient mutant of Aeromonas hydrophila in lake water
      microcosms were performed. Growth of both strains did not differ in single
      cultures and showed no mutual influence in co-cultures. In co-cultures with a
      competitor bacterium belonging to the Cytophaga-Flavobacterium group, growth of
      both A. hydrophila strains was reduced while growth of the competitor bacterium
      was not affected. Exogenous AHL-addition did not influence growth of the
      Aeromonas strains in any microcosm experiment. These results showed that AHL
      mediated QS was not required for A. hydrophila during colonization and
      degradation of organic particles in lake water microcosms, suggesting that cell
      cell signalling of heterotrophic bacteria in oligotrophic waters relies on novel
      signal molecules.

PMID- 18066532
TI  - Pharmacological properties of a wide array of ergolines at functional alpha(1)
      adrenoceptor subtypes.
AB  - Ergot alkaloids act as (partial) agonists or antagonists at serotonergic,
      dopaminergic and alpha-adrenergic receptors. In contrast to their affinity at
      serotonergic (5-HT) and dopaminergic receptor subtypes, only limited information
      is available concerning their interaction with alpha-adrenoceptor subtypes. This
      especially holds true for native alpha-adrenoceptors. Therefore, we studied the
      pharmacological profile of 25 ergolines at alpha(1A)-, alpha(1B)- and alpha(1D)
      adrenoceptors in vascular rings or strips of rat and guinea pig endowed with
      these receptors. Contractile responses were studied by measurement of isometric
      tension changes in rat tail artery (alpha(1A), alpha(1B)), guinea pig spleen
      (alpha(1B)) and rat thoracic aorta (alpha(1D)). The anti-migraine drugs
      ergotamine and dihydroergotamine, the anti-parkinsonian drug lisuride and the
      anti-hyperprolactinemic drug terguride behaved as antagonists or low-efficacy
      partial agonists at all three alpha(1)-adrenoceptor subtypes with nanomolar
      receptor affinity. Derivatives of these drugs showed lower affinity at alpha(1)
      adrenoceptors than the parent compounds. Each individual ergoline derivative
      tested showed low discriminatory capability at the subtypes, alpha(1A),
      alpha(1B), alpha(1D). A low discriminatory power between the subtypes (alpha(1A),
      alpha(1B), alpha(1D)) seems to be a class effect of the ergolines. The nanomolar
      affinities of ergotamine, dihydroergotamine and lisuride for alpha(1)
      adrenoceptors may affect their effectiveness as anti-migraine and anti
      parkinsonian drugs, respectively.

PMID- 18066533
TI  - Opposing roles for the ventral prefrontal cortex and the basolateral amygdala on
      the spontaneous recovery of cocaine-seeking in rats.
AB  - RATIONALE: The neural circuitry subserving cocaine-seeking after extinction vs
      abstinence alone requires different constituent brain structures. Spontaneous
      recovery of cocaine-seeking, a model, which incorporates both extinction and
      abstinence, depends on an unknown neural circuit. OBJECTIVES: The present study
      examined the hypothesis that the spontaneous recovery of cocaine-seeking would
      require overlapping but distinct neural circuits compared to models that
      incorporate either extinction or abstinence alone. MATERIAL AND METHODS: Rats
      were trained to self-administer cocaine (0.2 mg/inf), then responding on the
      cocaine-paired lever was extinguished, followed by an additional period of
      abstinence in the home cage. Finally, rats were returned to the self
      administration context for a test of spontaneous recovery (SR TEST). Just before
      the SR TEST, discrete brain regions were inactivated with a GABA agonist cocktail
      (1 mM baclofen + 0.1mM muscimol) to determine the relative importance of these
      brain regions in the spontaneous recovery of cocaine-seeking. RESULTS: The
      inactivation of the ventromedial prefrontal cortex (vPFC) enhanced cocaine
      seeking, whereas the inactivation of the basolateral amygdala (BLA) attenuated
      spontaneous recovery. Inactivation of the nucleus accumbens core (Core) resembled
      the effects of BLA inactivation, but these results were confounded by an
      inhibitory effect of the vehicle treatment. Finally, the spontaneous recovery of
      cocaine-seeking was unaltered by manipulations of the dorsomedial prefrontal
      cortex (dPFC) and the nucleus accumbens shell (Shell). CONCLUSIONS: The neural
      circuitry subserving cocaine-seeking behavior in a spontaneous recovery model
      requires the BLA and possibly the Core, like extinction models. In addition, this
      behavior is subject to regulation by vPFC, in a manner functionally opposite to
      that of the BLA.

PMID- 18066534
TI  - Acquisition and maintenance of cocaine self-administration in adolescent rats:
      effects of sex and gonadal hormones.
AB  - RATIONALE: Previous work has shown that adult female rats are more sensitive than
      adult male rats to the reinforcing effects of cocaine, an effect that appears to
      be due, at least in part, to ovarian hormones. OBJECTIVE: In this study, we
      examine sex differences in cocaine self-administration during adolescence, a
      period of marked hormonal change. MATERIALS AND METHODS: Adolescent male and
      female Sprague-Dawley rats were trained to self-administer cocaine (0.75 mg/kg
      per infusion) under a fixed ratio 1 schedule (i.e., each response was reinforced
      by an infusion of cocaine) beginning on postnatal day 30. After acquisition,
      responding was assessed under a progressive-ratio schedule until postnatal day 50
      with blood sampling occurring before the first five sessions to determine the
      relationship between gonadal hormones (i.e., estradiol, progesterone, and
      testosterone) and motivation for cocaine. Estrous cycle phase was monitored
      throughout the study. Separate groups of adolescent male and female rats were
      compared on the acquisition of and progressive-ratio responding for sucrose
      reinforcement. RESULTS: Females acquired cocaine self-administration more readily
      than did males, and a greater percentage of females acquired self-administration.
      Under progressive-ratio testing conditions, adolescent females responded at
      higher levels than adolescent males to obtain cocaine infusions, and in females,
      responding was positively associated with levels of estradiol and greatest during
      estrus. No sex differences were observed for sucrose reinforcement. CONCLUSION:
      These findings suggest that sex differences are relevant during adolescence with
      evidence implicating circulating estradiol level as a factor that contributes to
      the enhanced sensitivity in females to the reinforcing effects of cocaine.

PMID- 18066535
TI  - Effects of a low dose of alcohol on cognitive biases and craving in heavy
      drinkers.
AB  - RATIONALE: Heavy alcohol drinking increases the incentive salience of alcohol
      related cues. This leads to increased appetitive motivation to drink alcohol as
      measured by subjective craving and cognitive biases such as attentional bias and
      approach bias. Although these measures relate to the same construct, correlations
      between these variables are often very low. Alcohol consumption might not only
      increase different aspects of appetitive motivation, but also correlations
      between those aspects. OBJECTIVES: To investigate the effect of a low alcohol
      dose on changes in various measures of appetitive motivation. MATERIALS AND
      METHODS: Twenty-three heavy social drinkers were tested in 2 sessions, once after
      receiving an alcohol prime dose and once after receiving a placebo drink. After
      drink administration, attentional bias was measured with a visual-probe task
      using concurrent eye movement monitoring. Furthermore, we measured the approach
      bias with a stimulus response compatibility task and subjective craving with the
      Desires for Alcohol Questionnaire. RESULTS: After the alcohol prime dose,
      participants had higher levels of craving and more pronounced attentional bias
      (faster reaction times to probes that replaced alcohol rather than control
      pictures, increased maintenance of gaze on alcohol pictures, and a higher
      percentage of first eye movements directed toward alcohol pictures). Approach
      bias was not influenced by the alcohol prime dose. The correlation between
      attentional bias and approach bias was significantly higher after the alcohol
      than after the placebo drink. CONCLUSIONS: A low alcohol dose increased most
      measures of appetitive motivation for alcohol and increased the interrelation
      between cognitive measures of this construct.

PMID- 18066536
TI  - Participation of hippocampal ionotropic glutamate receptors in histamine H(1)
      antagonist-induced memory deficit in rats.
AB  - RATIONALE: Pyrilamine, a selective histamine H(1) antagonist, impaired spatial
      memory, and decreased hippocampal theta activity during a radial maze task.
      OBJECTIVE: We investigated the ameliorative effects of glutamatergic drugs on
      pyrilamine-induced spatial memory deficit and the decrease in hippocampal theta
      activity in rats. MATERIALS AND METHODS: Drug effects were measured using an
      eight-arm radial maze with four arms baited. Hippocampal theta rhythm during the
      radial maze task was also recorded with a polygraph system using a telemetric
      technique. RESULTS: Intraperitoneal injection of pyrilamine (35 mg/kg) resulted
      in impaired reference and working memory in the radial maze task and a decrease
      in the amplitude and power of hippocampal theta waves. The working memory deficit
      and the decrease in hippocampal theta power were antagonized by intrahippocampal
      injection of D: -cycloserine (1 microg/side), spermidine (10 microg/side),
      spermine (10 microg/side), aniracetam (1 microg/side), and 1-(1,3-benzodioxol-5
      ylcarbonyl) piperidine (1-BCP) (1 microg/side), but not concanavalin A.
      CONCLUSION: These results clearly indicate that H(1) antagonist-induced working
      memory deficit, and the decrease in hippocampal theta activity was closely
      associated with hippocampal glutamatergic neurotransmission mediated by N-methyl
      D: -aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) receptors.

PMID- 18066537
TI  - Analysis of cocaine and its principal metabolites in waste and surface water
      using solid-phase extraction and liquid chromatography-ion trap tandem mass
      spectrometry.
AB  - A validated method based on solid-phase extraction (SPE) and liquid
      chromatography-ion trap tandem mass spectrometry (LC-MS/MS) is described for the
      determination of cocaine (COC) and its principal metabolites, benzoylecgonine
      (BE) and ecgonine methyl ester (EME), in waste and surface water. Several SPE
      adsorbents were investigated and the highest recoveries (95.7 +/- 5.5, 91.8 +/-
      2.2 and 72.5 +/- 5.3% for COC, BE and EME, respectively) were obtained for OASIS
      HLB(R) cartridges (6 mL/500 mg) using 100 mL of waste water or 500 mL of surface
      water. Extracts were analysed by reversed-phase (RP) or hydrophilic interaction
      (HILIC) LC-MS/MS in positive ion mode with multiple reactions monitoring (MRM);
      the latter is the first reported application of the HILIC technique for drugs of
      abuse in water samples. Corresponding deuterated internal standards were used for
      quantification. The method limits of quantification (LOQs) for COC and BE were 4
      and 2 ng L(-1), respectively, when RPLC was used and 1, 0.5 and 20 ng L(-1) for
      COC, BE and EME, respectively, with the HILIC setup. For COC and BE, the LOQs
      were below the concentrations measured in real water samples. Stability tests
      were conducted to establish the optimal conditions for sample storage (pH,
      temperature and time). The degradation of COC was minimal at -20 degrees C and pH
      = 2, but it was substantial at +20 degrees C and pH = 6. The validated method was
      applied to a set of waste and surface water samples collected in Belgium.

PMID- 18066538
TI  - Gravitation-driven stress-reduced cell handling.
AB  - We present a simple lab-on-chip device for handling small samples of delicate
      cells, e.g. stem cells. It uses a combination of sedimentation and
      dielectrophoresis. The transport of cells is driven by gravitation.
      Dielectrophoresis uses radio-frequency electric fields for generating particle
      selective forces dependent on size and polarisability. Electrodes along the
      channels hold particles and/or cells in a defined position and deflect them
      towards different outlets. The absence of external pumping and the integration of
      injection and sampling ports allow the processing of tiny sample volumes. Various
      functions are demonstrated, such as contact-free cell trapping and cell/particle
      sorting. Pairs of human cells and antibody-coated beads, as they are formed for T
      cell activation, are separated from unbound beads. The cells experience only low
      stress levels compared with the stress levels in dielectrophoresis systems, where
      transport depends on external pumping. Our device is a versatile yet simple tool
      that finds applications in cellular biotechnology, in particular when an economic
      solution is required.

PMID- 18066539
TI  - Electrospun polymer nanofibers as a solid-phase extraction sorbent for the
      determination of trace pollutants in environmental water.
AB  - This paper describes the novel preparation of three kinds of nanofibers
      [poly(styrene-co-methacrylic acid), poly(styrene-co-p-styrene sulfonate),
      polystyrene] investigated as solid-phase extraction (SPE) sorbents to extract six
      compounds (nitrobenzene, 2-naphthol, benzene, n-butyl p-hydroxybenzoate,
      naphthalene, p-dichlorobenzene) in environmental water by high-performance liquid
      chromatography. Parameters affecting extraction efficiency were investigated in
      detail to explore the extraction mechanism of the nanofibers. Under optimized
      conditions, six compounds followed an excellent linear relationship in the range
      10-5,000 ng mL(-1) with coefficients of determination (r (2)) greater than 0.99.
      The repeatability (expressed as relative standard deviations) was from 3.0 to
      7.0%, corresponding to 2.0 mL of water samples at 25 and 500 ng mL(-1) spiked
      levels for the six compounds. The limits of detection varied from 0.01 to 0.15 ng
      mL(-1) (signal-to-noise ratio of 3). A comparison of the SPE using nanofibers as
      sorbents and the most commonly used octadecylsilica SPE cartridges was carried
      out in terms of absolute recovery, sensitivity, and reproducibility for the
      compounds investigated. Finally, the method was applied to four real water
      samples. The results highlighted the importance of functional groups, and the
      polarity of nanofibers in controlling sorption of target compounds, and clearly
      showed that the new method could be a viable and environmentally friendly
      technique for analyzing pollutants in environmental samples.

PMID- 18066540
TI  - Smoothing and passivation of special Si(111) substrates: studied by SPV, PL, AFM
      and SEM measurements.
AB  - Surface sensitive techniques, the field-modulated surface photovoltage,
      photoluminescence measurements, atomic force microscopy and scanning electron
      microscopy, were employed to yield detailed information on the influence of wet
      chemical treatments on the preparation induced microroughness and electronic
      properties of wet-chemically passivated Si(111) substrates with special surface
      morphology. Stepped substrates with evenly distributed atomically flat terraces
      were prepared and passivated by thin oxide layers, which were used as a starting
      point for the subsequent H-termination after long storage in air. It was shown
      that their surface morphology and electronic properties do not degrade. Applying
      this preparation method to solar cell substrates with randomly distributed
      Si(111) pyramids, we achieved significantly lower densities of surface states and
      reduced recombination loss at a-Si:H/c-Si interfaces, compared with conventional
      pretreatments. The surface microroughness, the density of rechargeable states and
      the resulting recombination loss on a-Si:H/c-Si heterojunctions were found to be
      mainly influenced by two steps of surface pretreatment: firstly, the wet-chemical
      smoothing procedure of structured substrates and, secondly, the removal of native
      and wet-chemical oxides during the final etching in HF- or NH(4)F-containing
      solutions.

PMID- 18066541
TI  - Labyrinthine dehiscence in a child.
AB  - A 4-year-old boy presented with moderate to profound mixed hearing loss in the
      right ear and moderate to severe mixed hearing loss in the left ear, prompting a
      temporal bone CT scan. Images revealed partial dehiscence of the right posterior
      semicircular canal. Semicircular canal dehiscence and its associated clinical
      syndrome have been described in adults. We present this case as a unique finding
      in a child and discuss the possible clinical and research implications.

PMID- 18066543
TI  - Langerhans cell histiocytosis of the epiphysis.

PMID- 18066542
TI  - Paediatric CT: the effects of increasing image noise on pulmonary nodule
      detection.
AB  - BACKGROUND: A radiation dose of any magnitude can produce a detrimental effect
      manifesting as an increased risk of cancer. Cancer development may be delayed for
      many years following radiation exposure. Minimizing radiation dose in children is
      particularly important. However, reducing the dose can reduce image quality and
      may, therefore, hinder lesion detection. OBJECTIVE: We investigated the effects
      of reducing the image signal-to-noise ratio (SNR) on CT lung nodule detection for
      a range of nodule sizes. MATERIALS AND METHODS: A simulated nodule was placed at
      the periphery of the lung on an axial CT slice using image editing software.
      Multiple copies of the manipulated image were saved with various levels of
      superimposed noise. The image creation process was repeated for a range of nodule
      sizes. For a given nodule size, output images were read independently by four
      Fellows of The Royal College of Radiologists. RESULTS: The overall sensitivities
      in detecting nodules for the SNR ranges 0.8-0.99, 1-1.49, and 1.5-2.35 were
      40.5%, 77.3% and 90.3%, respectively, and the specificities were 47.9%, 73.3% and
      75%, respectively. The sensitivity for detecting lung nodules increased with
      nodule size and increasing SNR. There was 100% sensitivity for the detection of
      nodules of 4-10 mm in diameter at SNRs greater than 1.5. CONCLUSION: Reducing
      medical radiation doses in children is of paramount importance. For chest CT
      examinations this may be counterbalanced by reduced sensitivity and specificity
      combined with an increased uncertainty of pulmonary nodule detection. This study
      demonstrates that pulmonary nodules of 4 mm and greater in diameter can be
      detected with 100% sensitivity provided that the perceived image SNR is greater
      than 1.5.

PMID- 18066544
TI  - Efficient production of canine interferon-alpha in silkworm Bombyx mori by use of
      a BmNPV/Bac-to-Bac expression system.
AB  - We exploited the silkworm Bombyx mori for the production of recombinant canine
      interferon-alpha (CaIFN-alpha). The recombinant baculovirus harboring canine
      interferon gene was rapidly generated by the BmNPV/Bac-to-Bac system that was
      recently developed. In B. mori-derived cell lines, the expression of the
      recombinant protein reached maximal levels around 72-96 h post-infection. For the
      isolation of the expressed recombinant protein from B. mori larvae, the whole
      bodies of the infected larvae were homogenized, and the expressed protein was
      purified by affinity chromatography. Based on the fact that the recombinant CaIFN
      alpha showed two bands on the sodium dodecyl sulfate polyacrylamide gel
      electrophoresis pattern, the expressed protein was thought to be glycosylated.
      The rCaIFN-alpha yield was about 528 microg per larva, showing that the
      expression in silkworm was successful. Furthermore, the recombinant protein was
      proven to be able to inhibit the infection of Madin-Darby canine kidney cells by
      the vesicular stomatitis virus, indicating that it is biologically active in
      vitro. The method established in this study provides an efficient way to produce
      a large amount of CaIFN-alpha and paves the way for further utilization of this
      protein as a therapeutic agent or vaccine adjuvant in dogs.

PMID- 18066545
TI  - A small protein that fights fungi: AFP as a new promising antifungal agent of
      biotechnological value.
AB  - As fungal infections are becoming more prevalent in the medical or agricultural
      fields, novel and more efficient antifungal agents are badly needed. Within the
      scope of developing new strategies for the management of fungal infections,
      antifungal compounds that target essential fungal cell wall components are highly
      preferable. Ideally, newly developed antimycotics should also combine major
      aspects such as sustainability, high efficacy, limited toxicity and low costs of
      production. A naturally derived molecule that possesses all the desired
      characteristics is the antifungal protein (AFP) secreted by the filamentous
      ascomycete Aspergillus giganteus. AFP is a small, basic and cysteine-rich peptide
      that exerts extremely potent antifungal activity against human- and plant
      pathogenic fungi without affecting the viability of bacteria, yeast, plant and
      mammalian cells. This review summarises the current knowledge of the structure,
      mode of action and expression of AFP, and highlights similarities and differences
      concerning these issues between AFP and its related proteins from other
      Ascomycetes. Furthermore, the potential use of AFP in the combat against fungal
      contaminations and infections will be discussed.

PMID- 18066547
TI  - Primary cardiac onset of disseminated Burkitt's lymphoma.

PMID- 18066548
TI  - Pharmacokinetics of oral fenretinide in neuroblastoma patients: indications for
      optimal dose and dosing schedule also with respect to the active metabolite 4-oxo
      fenretinide.
AB  - PURPOSE: Pharmacokinetic data on fenretinide (4-HPR) are scant, thus limiting the
      rational use of the drug. We investigated the pharmacokinetics of 4-HPR and its
      active metabolite 4-oxo-fenretinide (4-oxo-4-HPR). EXPERIMENTAL DESIGN:
      Pharmacokinetics were assessed in 18 children (3 for each dose) with
      neuroblastoma who received oral 4-HPR once daily for 28 days at the doses of 100,
      300, 400, 600, 1,700 and 4,000 mg/m(2)/day. 4-HPR and 4-oxo-4-HPR were determined
      by HPLC in plasma collected up to 48 h after the first and 28th administration.
      RESULTS: After single administration, 4-HPR mean C (max) ranged from 0.9 to 6.6
      microM and these concentrations roughly doubled at steady state (range 1.6-14.5
      microM). 4-HPR mean t (1/2) was 22 h. 4-HPR pharmacokinetics were linear in the
      dose range 100-1,700 mg/m(2); less than dose-proportional increase in exposure
      was found at 4,000 mg/m(2). At steady state, pharmacologically relevant plasma
      concentrations (range 0.7-10 microM and 0.4-5 microM for 4-HPR and 4-oxo-4-HPR,
      respectively) were maintained during the 24 h dosing interval in the dose range
      300-4,000 mg/m(2). CONCLUSIONS: 4-HPR pharmacokinetics supports once-daily
      dosing. Steady state concentrations of 4-HPR and 4-oxo-4-HPR in children with
      neuroblastoma are in line with those found to have in vitro growth inhibitory
      effects in neuroblastoma cells.

PMID- 18066546
TI  - Iron and thrombosis.
AB  - Although essential for cell physiology, an increase or depletion of body iron has
      harmful effects on health. Apart from iron deficiency anemia and iron overload
      related organ tissue damage, there are increasing evidences that body iron status
      is implicated in atherosclerotic cardiovascular diseases. The hypothesis
      formulated in 1981 that iron depletion may protect against cardiovascular events
      is intriguing and has generated a significant debate in the last two decades.
      Indeed, to study this phenomenon, several investigators have tried to design
      appropriate experimental and clinical studies and to identify useful biochemical
      and genetic markers of iron status. The results of the literature on the effect
      of iron deficiency and overload on vascular health are critically reviewed in
      this study from a pathogenic and clinical point of view.

PMID- 18066549
TI  - Two peptides derived from ras-p21 induce either phenotypic reversion or tumor
      cell necrosis of ras-transformed human cancer cells.
AB  - PURPOSE: We investigated the effects of two peptides from the ras-p21 protein,
      corresponding to residues 35-47 (PNC-7) and 96-110 (PNC-2), on two ras
      transformed human cancer cell lines, HT1080 fibrosarcoma and MIAPaCa-2 pancreatic
      cancer cell lines. In prior studies, we found that both peptides block oncogenic,
      but not insulin-activated wild-type, ras-p21-induced oocyte maturation. When
      linked to a transporter penetratin peptide, these peptides induce reversion of
      ras-transformed rat pancreatic cancer cells (TUC-3) to the untransformed
      phenotype. METHODS: These peptides and a control peptide, linked to a penetratin
      peptide, were incubated with each cell lines. Cell counts were obtained over
      several weeks. The cause of cell death was determined by measuring caspase as an
      indicator of apoptosis and lactate dehydrogenase (LDH) as marker of necrosis.
      Since both peptides block the phosphorylation of jun-N-terminal kinase (JNK) in
      oocytes, we blotted cell lysates of the two cancer cell lines for the levels of
      phosphorylated JNK to determine if the peptides reduced these levels. RESULTS: We
      find that both peptides, but not control peptides linked to the penetratin
      sequence, induce phenotypic reversion of the HT-1080 cell line but cause tumor
      cell necrosis of the MIA-PaCa-2 cell line. On the other hand, neither peptide has
      any effect on the viability of an untransformed pancreatic acinar cell line,
      BMRPA1. We find that, while total JNK levels remain constant during peptide
      treatment, phosphorylated JNK levels decrease dramatically, consistent with the
      mechanisms of action of these peptides. CONCLUSION: We conclude that these
      peptides block tumor but not normal cell growth likely by blocking oncogenic ras
      p21-induced phosphorylation of JNK, an essential step on the oncogenic ras-p21
      protein pathway. These peptides are therefore promising as possible anti-tumor
      agents.

PMID- 18066550
TI  - Toll like receptor-5: protecting the gut from enteric microbes.
AB  - The intestine is normally colonized by a large and diverse commensal microbiota
      and is occasionally exposed to a variety of potential pathogens. In recent years,
      there has been substantial progress made in identifying molecular mechanisms that
      normally serve to protect the intestine from such enteric bacteria and which may
      go awry in chronic idiopathic inflammatory diseases of the gut. One specific
      molecular interaction that appears to play a key role in governing bacterial
      intestinal interactions is that of the bacterial protein flagellin with toll-like
      receptor 5. This article reviews studies performed in vitro, in mice, and in
      humans that indicate an important role for the flagellin-TLR5 interaction in
      regulating both the innate and adaptive immune responses in the intestine.

PMID- 18066551
TI  - Onset and enhancement of systemic sclerosis after treatments for multiple
      sclerosis.
AB  - The coexistence of systemic sclerosis (SSc) and multiple sclerosis (MS) in the
      same patient has been described in few cases. We refer here a further case of
      association between these diseases, which highlight the difficulty of treating
      such patients. A 57-year-old male with relapsing-remitting MS since 20 years,
      shortly after having received high-dose corticosteroids for a relapse of MS,
      suddenly developed SSc, with onset of Raynaud phenomenon simultaneous to that of
      scleroderma skin involvement, new appearance of accelerated arterial
      hypertension, and rapidly progressive oliguric renal failure, indicative of
      scleroderma renal crisis, that was controlled with ramipril, irbesartan and
      amlodipin. A further disabling relapse of MS was treated with interferon-beta,
      but 19 months later he developed multiple severe digital necrotic ulcers, that
      resolved with interferon discontinuation and therapy with iloprost. This case
      report shows that some form of treatment useful for MS might enhance the
      manifestations of SSc.

PMID- 18066552
TI  - Dermatological manifestations associated with microscopic polyangiitis.
AB  - Microscopic polyangiitis (MPA) is a systemic small vessel vasculitis, which,
      although primarily associated with necrotizing and crescentic glomerulonephritis
      and pulmonary capillaritis, often has cutaneous and musculoskeltal features.
      Although the skin is affected in 20-70% of patients, the precise description has
      been limited. This retrospective study analyzed clinical manifestations in
      patients of MPA with skin eruptions.

PMID- 18066553
TI  - Dynamics of phenolic acids and lignin accumulation in metal-treated Matricaria
      chamomilla roots.
AB  - Phenylalanine ammonia-lyase (PAL) activity, 11 phenolic acids and lignin
      accumulation in Matricaria chamomilla roots exposed to low (3 microM) and high
      (60 and 120 microM) levels of cadmium (Cd) or copper (Cu) for 7 days were
      investigated. Five derivatives of cinnamic acid (chlorogenic, p-coumaric,
      caffeic, ferulic and sinapic acids) and six derivatives of benzoic acid
      (protocatechuic, vanillic, syringic, p-hydroxybenzoic, salicylic acids and
      protocatechuic aldehyde) were detected. Accumulation of glycoside-bound phenolics
      (revealed by acid hydrolysis) was enhanced mainly towards the end of the
      experiment, being more expressive in Cu-treated roots. Interestingly, chlorogenic
      acid was extremely elevated by the highest Cu dose (21-fold higher than control)
      suggesting its involvement in antioxidative protection. All compounds, with the
      exception of chlorogenic acid, were detected in the cell wall bound fraction, but
      only benzoic acids were found in the ester-bound fraction (revealed by alkaline
      hydrolysis). Soluble phenolics were present in substantially higher amounts in Cu
      treated roots and more Cu was retained there in comparison to Cd. Cu strongly
      elevated PAL activity (by 5.4- and 12.1-fold in 60 and 120 microM treatment,
      respectively) and lignin content (by 71 and 148%, respectively) after one day of
      treatment, indicating formation of a barrier against metal entrance. Cd had
      slighter effects, supporting its non-redox active properties. Taken together,
      different forms of phenolic metabolites play an important role in chamomile
      tolerance to metal excess and participate in active antioxidative protection.

PMID- 18066554
TI  - Functional characterization of a cotton late embryogenesis-abundant D113 gene
      promoter in transgenic tobacco.
AB  - Previous studies have shown that mRNA and protein encoded by late embryogenesis
      abundant (LEA) gene D113 from Gossypium hirsutum L. accumulate at high levels in
      mature seeds and also in response to abscisic acid (ABA) in young embryo. In this
      study, we studied the expression of four promoter 5' deletion constructs (-1383, 
      974, -578 and -158) of the LEA D113 gene fused to beta-glucuronidase (GUS). GUS
      activity analysis revealed that the -578 promoter fragment was necessary to
      direct seed-specific GUS expression in transgenic tobacco plants (Nicotiana
      tabacum L.). To further investigate the expression pattern of LEA D113 promoter
      under environmental stresses, 2-week-old transgenic tobacco seedlings were
      exposed to ABA, dehydration, high salinity and cold treatments. GUS activity in
      the seedlings was quantified fluorimetrically, and expression was also observed
      by histochemical staining. An apparent increase in GUS activity was found in
      plants harboring constructs -1383, -974 and -578 after 24 h of ABA or high
      salinity treatments, as well as after 10 days of dehydration. By contrast, only a
      slight increase was observed in all the three lines after cold treatment.
      Virtually no change in expression was found in construct -158 in response to
      dehydration, salinity and cold, but there was a moderate response to ABA,
      suggesting that the region between -574 and -158 was necessary for dehydration-
      and salinity-dependent expression, whereas ABA-responsive cis-acting elements
      might be located in the -158 region of the promoter.

PMID- 18066555
TI  - Validation of a Monte Carlo tool for patient-specific dose simulations in multi
      slice computed tomography.
AB  - Estimating the dose delivered to the patient in X-ray computed tomography (CT)
      examinations is not a trivial task. Monte Carlo (MC) methods appear to be the
      method of choice to assess the 3D dose distribution. The purpose of this work was
      to extend an existing MC-based tool to account for arbitrary scanners and scan
      protocols such as multi-slice CT (MSCT) scanners and to validate the tool in
      homogeneous and heterogeneous phantoms. The tool was validated by measurements on
      MSCT scanners for different scan protocols under known conditions. Quantitative
      CT Dose Index (CTDI) measurements were performed in cylindrical CTDI phantoms and
      in anthropomorphic thorax phantoms of various sizes; dose profiles were measured
      with thermoluminescent dosimeters (TLD) in the CTDI phantoms and compared with
      the computed dose profiles. The in-plane dose distributions were simulated and
      compared with TLD measurements in an Alderson-Rando phantom. The calculated dose
      values were generally within 10% of measurements for all phantoms and all
      investigated conditions. Three-dimensional dose distributions can be accurately
      calculated with the MC tool for arbitrary scanners and protocols including tube
      current modulation schemes. The use of the tool has meanwhile also been extended
      to further scanners and to flat-detector CT.

PMID- 18066556
TI  - Efficacy of superficial temporal artery-middle cerebral artery anastomosis with
      routine postoperative cerebral blood flow measurement during the acute stage in
      childhood moyamoya disease.
AB  - OBJECT: Surgical revascularization for moyamoya disease prevents cerebral
      ischemic attacks by improving cerebral blood flow (CBF). It is undetermined,
      however, how rapid increase in CBF affects chronic ischemic brain during the
      acute stage in childhood moyamoya disease. MATERIALS AND METHODS: The present
      study includes nine consecutive cases of patients with childhood moyamoya disease
      (2 to approximately 8 years old, 6.2 in average), who underwent superficial
      temporal artery-middle cerebral artery (STA-MCA) anastomosis on 17 hemispheres.
      We prospectively performed single-photon emission computed tomography 1 and 7
      days after 17 surgeries. The follow-up period ranged from 12 to 37 months (24.9
      in average). RESULTS: The outcome of 17 surgeries was excellent (disappearance of
      transient ischemic attack) in 14 hemispheres (82.4%) and good (reduction of
      transient ischemic attack) in three hemispheres (17.6%). No patient suffered peri
      operative infarction, except for one (5.9%) manifesting as pseudolaminar necrosis
      in a part of the cerebral cortex supplied by STA-MCA bypass at the subacute
      stage, which did not affect his long-term neurological status. One patient (5.9%)
      presented with transient facial palsy due to hyperperfusion, which resolved
      within several days. No patient manifested permanent neurological deterioration
      during the follow-up period. CONCLUSION: The STA-MCA anastomosis is a safe and
      effective treatment for childhood moyamoya disease. We recommend routine CBF
      measurement for avoiding surgical complications including both cerebral ischemia
      and hyperperfusion.

PMID- 18066557
TI  - Spontaneous third ventriculostomy in chronic obstructive hydrocephalus.
AB  - INTRODUCTION: Spontaneous ventriculostomy is a rare condition, and only few cases
      are reported. Cine magnetic resonance imaging can demonstrate the flow from the
      ventriculostomy. CASE REPORT: A 25-year-old woman with a known tectal glioma and
      hydrocephalus was proved to have spontaneous third ventriculostomy.

PMID- 18066558
TI  - Hans Chiari (1851-1916).

PMID- 18066559
TI  - MAPT S305I mutation: implications for argyrophilic grain disease.
AB  - Frontotemporal lobar degeneration (FTLD) with mutations in the tau gene (MAPT)
      causes familial frontotemporal dementia with tau pathology. Many of these
      mutations result in morphological phenotypes resembling sporadic tauopathies,
      although, to date, no such cases mimicking argyrophilic grain disease (AgD) have
      been documented. We now present a case with a novel S305I MAPT mutation and a
      morphological phenotype showing resemblance to AgD. At the age of 39, the patient
      developed behavioural and personality changes and lack of verbal fluency with
      later poor performance on naming tasks and rigidity in the extremities. After a
      short disease course of 1.5 years, the patient died. A unique neuropathological
      phenotype with neuronal diffuse cytoplasmic tau immunoreactivity,
      oligodendroglial-coiled bodies, argyrophilic grains, and non-argyrophilic, but
      tau-immunopositive and ubiquitin-immunonegative pre-grains were observed, whereas
      classical neurofibrillary tangles, Pick bodies, and neuritic plaques were absent.
      The tau-positive abnormal structures were composed only of 4R-tau isoforms and,
      ultrastructurally, straight filaments. Neuronal loss was greatest in the medial
      temporal cortex, hippocampus, and amygdala. These pathological features resemble
      AgD. The novel S305I substitution has a strong effect on MAPT exon 10 splicing,
      thereby causing a striking increase in 4R-tau isoforms. Our observation not only
      widens the phenotypic spectrum of FTLD with MAPT mutation but also underpins the
      notion that the predominance of similar neuropathological findings in sporadic
      AgD cases may be viewed as features of a distinct disease entity.

PMID- 18066560
TI  - Dedifferentiated chondrosarcoma of the thumb: a case report.
AB  - Dedifferentiated chondrosarcoma (DDCS) comprises approximately 10% of all
      chondrosarcomas and has the worst outcome with 5-year survival of 10%. The
      preferred localizations are femur, humerus and pelvis. We report a case of DDCS
      that arose in proximal phalanx of left-hand thumb of a 66-year-old man. He was
      admitted with a 2-month history of pain and swelling in his thumb. He had
      experienced a fracture 15 years ago in the same localization with a history of
      suspected preexisting enchondroma. Plain radiographs showed an expansive
      osteolytic lesion with milimetric calcifications while magnetic resonance imaging
      revealed intraosseous focal globular hyperintense spots consistent with chondroid
      areas as well as a surrounding soft tissue mass with intermediate signal
      intensity. In biopsy specimen we observed a low-grade chondrosarcoma next to a
      spindle cell sarcoma with an abrupt transition. He was treated with amputation
      and died of the disease within 9 months following the surgery. The presence of
      dedifferented chondrosarcoma in bones of hands was not previously reported. The
      presented case was provided with the macroscopic and microscopic features
      observed in amputation specimen in comparison with radiological findings.

PMID- 18066561
TI  - Fracture of a ceramic liner in a total hip arthroplasty with a sandwich cup.
AB  - Alumina ceramic-on-ceramic total hip arthroplasty (THA) has been widely used due
      to its advantages such as low wear, scratch resistance, wettable surface and
      relatively low biological reactivity of the wear particles. Nevertheless, this
      material in THA still persists to be one of the major concerns about the risk of
      fracture, due to its brittleness. Many authors have reported a fracture of the
      ceramic head but few reported a fracture of the ceramic acetabular insert. In
      order to reduce the rigidity of the ceramic-on-ceramic coupling and prevent an
      impingement between the rim of the ceramic liner and the metal neck of the
      femoral stem, a modular acetabular component with a sandwich insertion
      (alumina/polyethylene/titanium) was proposed. We report the fracture of the
      ceramic acetabular liner of such a ceramic sandwich cup due to a slightly
      retroverted position of the cup that causes an impingement between the femoral
      stem and the rim of the insert. The fracture occurred 3 years after the operation
      without trauma. At revision the entire cup was replaced using a polyethylene
      liner without inner ceramic liner.

PMID- 18066562
TI  - The clinical significance of bleeding during the second trimester of pregnancy.
AB  - OBJECTIVE: This study aimed at investigating the clinical importance and
      pregnancy outcome in women suffering from bleeding during the second half of
      their pregnancies. METHODS: A population-based study including all deliveries
      between the years 1988 and 2005 was conducted. Comparison was performed between
      patients with and without vaginal bleeding during the second half of pregnancy.
      Pregnancies, which terminated before 22 weeks, multiple gestations and women
      lacking prenatal care were excluded from the analysis. Stratified analyses, using
      the Mantel-Haenszel technique, and a multiple logistic regression model were
      performed to control for confounders. RESULTS: During the study period, 175,093
      singleton deliveries occurred in our institute. Of these, 2,010 (1.1%) were
      complicated with bleeding upon admission during the second half of pregnancy. The
      cases were mostly attributed to placental abruption (63.5%; n = 1,276) and
      placenta previa (36.5%; n = 734). Independent risk factors associated with
      bleeding, using a backward, stepwise multivariate analysis were oligohydramnios,
      polyhydramnions, [odds ratio (OR) = 1.6; 95% confidence interval (CI) 1.2-2.0; P
      = 001 and 1.5; 1.2-1.8; P < 0.01, respectively], suspected intra uterine growth
      restriction (IUGR, 3.2; 2.6-4.0; P < .001), gestational age, previous abortions
      and maternal age. These patients subsequently were more likely to deliver by
      cesarean section (CS, 72.9 vs. 12.1%, OR = 19.5; 95% CI 17.6-19.9; 14.9 vs. 1.1%;
      P < 0.001). Perinatal mortality among patients admitted due to second half
      bleeding was significantly higher as compared to patients without bleeding (P <
      .001). CONCLUSION: Bleeding upon admission during the second half of pregnancy is
      an independent risk factor for perinatal mortality. Careful surveillance,
      including fetal monitoring, is suggested in these cases in order to reduce the
      adverse perinatal outcome.

PMID- 18066563
TI  - Unusually large extraintestinal GIST presenting as an abdomino-pelvic tumor.
AB  - BACKGROUND: Gastrointestinal stromal tumor (GIST) is a rare visceral tumor that
      may mimic ovarian tumor. CASE: A 56-year-old woman presented with a large
      abdomino-pelvic mass and moderately elevated CA-125. A large tumor occupying the
      whole abdominal cavity and pelvis was noted on laparotomy. In addition, multiple
      tumor nodules were seen from the ligament of Treitz to the terminal ileum
      involving only the surface intestine. The ovaries appeared normal. The tumor
      demonstrated spindle and epithelioid components and was found to be
      morphologically and immunohistochemically consistent with GIST. CONCLUSION:
      Gynecologists need to be cognizant of extra-ovarian pathology in the atypical
      presentation of a pelvic mass. Correct diagnosis is essential for proper
      management since GISTs specifically respond to the c-kit selective tyrosine
      kinase inhibitor, Imatinib mesylate.

PMID- 18066564
TI  - Endometrioid carcinoma of the endometrium with choriocarcinomatous
      differentiation: a case report and review of the literature.
AB  - OBJECTIVE: An endometrioid adenocarcinoma (EAC) with true trophoblastic
      differentiation is a rare event with a highly aggressive clinical course. CASE:
      We report an endometrioid adenocarcinoma of the endometrium in which there was a
      morphologically conventional-appearing EAC component admixed with multinucleated
      giant cells and large pleomorphic tumor cells that resembled a choriocarcinoma
      without an elevated serum level of human chorionic gonadotropin (hCG) in a 42
      year-old unmarried woman with a history of abnormal uterine bleeding. A total
      abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node
      dissection were performed. Histopathologic study of the specimen showed
      endometrioid adenocarcinoma extended to the deep myometrium with a focus of
      hemorrhagic and necrotic tumor composed of multinucleated giant cells, large
      pleomorphic tumor cells, suggesting choriocarcinomatous differentiation (CD).
      Immunohistochemical studies demonstrated intense reactivity of tumor cells for
      human chorionic gonadotropin (hCG) confirming the diagnosis. A complete clinical
      workup ruled out metastatic spread to the brain, lungs, skeleton, or abdomen. The
      patient was alive with no evidence of disease 6 months later. CONCLUSION:
      Although endometrioid adenocarcinoma with choriocarcinomatous differentiation is
      known to behave in a more aggressive course, this disease may have a good
      prognosis with a clinically indolent course when it is small, and without
      elevated serum hCG levels.

PMID- 18066565
TI  - Prediction of fetal anemia by Doppler of the middle cerebral artery and
      descending thoracic aorta.
AB  - BACKGROUND: Despite significant advances, perinatal hemolytic disease has not
      been eradicated and is still associated with significant morbidity and mortality,
      especially in developing countries. An accurate method for antenatal diagnosis
      and quantification of fetal anemia is a crucial step prior to the performance of
      invasive procedures, which are not risk-free. The middle cerebral artery peak
      systolic velocity (MCA-PSV) is currently the most popular non-invasive diagnostic
      method used to quantify fetal anemia and determine the exact timing for
      transfusion The combined use of MCA-PSV and descending thoracic aorta mean
      velocity (DTA-MV) has not been previously evaluated. Since this strategy has the
      potential to decrease false positive results it could reduce unnecessary
      cordocenteses, therefore minimizing fetal risks. This study aimed to evaluate the
      accuracy of MCA-PSV associated with DTA-MV in the prediction of fetal anemia.
      METHOD: Retrospective analysis of 90 cordocenteses performed on alloimmunized
      pregnancies in a single hospital MCA-PSV and DTA-MV were performed immediately
      before cordocentesis. The Dopplervelocimetry findings were compared with fetal
      hemoglobin concentration. Sensitivity, specificity, positive and negative
      predictive values and accuracy of MCA-PSV and DTA-MV in the prediction of
      moderate/severe fetal anemia were calculated. RESULTS: The individual sensitivity
      of MCA-PSV and DTA-MV was 100 and 95.7%, specificity was 65 and 100% and accuracy
      was 92.2 and 96.7%, respectively. The combination of both vessels produced a
      higher overall accuracy (98.6%). CONCLUSION: MCA-PSV is more sensitive and DTA-MV
      is more specific in the detection of fetal anemia. The highest diagnostic
      accuracy was obtained by the association of both Doppler evaluations.

PMID- 18066566
TI  - Effects of raloxifene and hormone replacement therapy on serum Th2 and Th3 type
      cytokine concentrations in healthy postmenopausal women: a randomised controlled
      trial.
AB  - BACKGROUND: Since sex hormones are reported to have important roles in the
      regulation of immune function, this study was designed to investigate the effects
      hormone replacement therapy (HRT) and raloxifene (RAL) on serum cytokine
      concentrations in healthy postmenopausal women. METHODS: Fifty-three healthy
      postmenopausal women were randomly assigned and treated by RAL (Group I, [RAL 60
      mg daily and continuously], n = 16), HRT (Group II, [2 mg estradiol valerat + 2
      mg dienogest, continuously] n = 18) or placebo (Group III, n = 19). Two fasting
      morning blood samples were obtained from each participant before and 3 months
      after the treatments. Serum concentration of interleukin (IL)-4 (as a Th2
      cytokine) and transforming growth factor-beta (TGF-beta)1 (as a Th3 cytokine),
      were measured by using commercially available enzyme-linked immunosorbent assay
      kits. Kruskal-Wallis analysis of variance, Mann-Whitney U, and Wilcoxon Signed
      Ranks Tests were used as necessary. RESULTS: At the beginning of the study, the
      chronological ages, menopausal ages, years of amenorrhea, weights, body mass
      indexes, and blood pressures were not significantly different between groups (P <
      0.05). RAL treatment caused a significant decrease on serum IL-4 concentration (P
      < 0.001). Although HRT caused a 14% decrease in serum IL-4 concentration, this
      decrease was not statistically significant (P > 0.05). Serum TGF-beta1
      concentrations were significantly decreased by HRT when compared to basal value
      (P < 0.001), and to control (P < 0.05). RAL treatment has no significant effect
      on serum TGF-beta1 concentration (P > 0.05). CONCLUSION: It seems that RAL
      treatment might cause a decrease in serum IL-4 concentration while valerate plus
      dienogest treatment as HRT seems to cause a Th3 tendency in healthy
      postmenopausal women.

PMID- 18066567
TI  - Four synchronous female genital malignancies: the ovary, cervix, endometrium and
      fallopian tube.
AB  - OBJECTIVE: To present a unique case of a 63 year-old woman with coexistent
      adenocarcinoma of the ovary, endometrium, cervix and fallopian tube. MATERIALS
      AND METHODS: A case report from a tertiary health center. RESULTS: A woman
      presenting with postmenopausal bleeding and abdominal distantion was assessed by
      endometrial biopsy and explorative surgery. The frozen section of the mass on the
      right adnex revealed malign mucinous carcinoma of the ovary. As usual, optimal
      debulking was performed as initial surgical staging procedure of ovarian cancer.
      The microscopic examination of the right ovary revealed a typical mucinous
      cystadenocarcinoma. Furthermore, the focal endometrial irregularity at the left
      uterine cornus turned out to be a well differentiated endometrial carcinoma of
      the endometrioid type with <1/3 myometrial invasion. The pale infiltrative lesion
      in the cervix also turned out to be an adenocarcinoma of the endocervical type
      with deep stromal invasion and areas of diffuse glandular dysplasia and in-situ
      glandular neoplasia at the periphery. Besides, several sections from the left
      fallopian tube uncovered diffuse dysplasia in the lining epithelium and a focus
      of adenocarcinoma with papillary and cribriform pattern. DISCUSSION: When
      compared with patients having metastatic lesions, most synchronous female
      malignancies are accompanied with early stage and low-grade with a more favorable
      prognosis. However, there is paucity of data for the exact criterion to
      distinguish primary tumors from metastatic lesions. In such cases, the validity
      of immunohistochemical and cloning studies are not clear.

PMID- 18066568
TI  - Skin metastases revealing a bilateral ovarian invasive micropapillary serous
      carcinoma.
AB  - Skin involvement is a late complication that rarely occurs in ovarian cancer
      patients. This event invariably carries a bad prognosis in the course of an
      advanced stage ovarian carcinoma which is usually of the conventional serous
      type. Micropapillary serous carcinoma (MPSC) was recently recognized as a
      distinct neoplasm that seems to be less aggressive than conventional serous
      ovarian carcinoma. Indeed, a few cases of stage IV MPSC have been reported.
      Herein, we describe an unusual case of ovarian invasive MPSC occurring in a young
      woman, particularly by its mode of presentation as multiple subcutaneous nodules
      that were subsequently diagnosed as metastatic lesions. This case demonstrates
      the potential of MPSC for aggressive clinical behaviour.

PMID- 18066569
TI  - Fetus with heart failure due to congenital atrioventricular block treated by
      maternally administered ritodrine.
AB  - BACKGROUND: The efficacy of maternal administration of ritodrine in cases of
      congenital atrioventricular block (CAVB), especially with fetal heart failure, is
      not yet determined. CASE: At 21 2/7 weeks of gestation, isolated CAVB with a
      ventricular/atrial rate of 55-70/130-140 bpm was found in a fetus from a 30-year
      old Japanese nulliparous woman with anti-SSA antibody. Cardiothoracic area ratio
      (CTAR) was 40% and no fetal hydrops was observed. At 30 2/7 weeks, the
      ventricular rate decreased to 49 bpm with an atrial rate of 125 bpm. CTAR
      increased to 53.8% and ascites appeared. Maternal continuous ritodrine infusion
      was started with rapid improvement of fetal cardiac function; increment in the
      ventricular rate to 57 bpm and atrial rate to 137 bpm, with a decrement in CTAR
      to 44.6%. Ascites also gradually decreased and by the fourth day, it had
      completely disappeared with CTAR of 40.2%. On the 12th day after ritodrine
      treatment (32 1/7), amniotic fluid volume decreased and fetal weight gain
      stopped, which led us to assume a worsening intrauterine environment, and
      cesarean section was performed. A 1,178 g male infant was born with a 5-min Apgar
      score of 8. Continuous isoproterenol infusion was started, increasing the
      ventricular rate from 71 to 80 bpm. Pacemaker implantation is under consideration
      to treat this infant. CONCLUSION: Maternal administration of ritodrine not only
      increased the fetal heart rate but also ameliorated the signs of fetal heart
      failure, and thus is considered one treatment of choice in CAVB.

PMID- 18066570
TI  - The electromyographic activity of the external and internal urethral sphincters
      and urinary bladder on vaginal distension and its role in preventing vaginal
      soiling with urine during sexual intercourse.
AB  - BACKGROUND/AIM: We investigated the hypothesis that external (EUS) and internal
      (IUS) urethral sphincters and urinary bladder (UB) respond to penile thrusting
      (PT) of vagina in a way that prevents urinary leakage during coitus. METHODS:
      Vaginal condom was inflated with air in increments of 50-300 ml and EMG of EUS
      and IUS and vaginal pressure were recorded; test was repeated after
      anesthetization of vagina, UB, EUS, and IUS. RESULTS: Vaginal distension effected
      reduction of vesical pressure but increase of IUS EMG until the 150 ml distension
      was reached, beyond which more vaginal distension caused no further effect; EUS
      EMG showed no response. Vaginal distension while vagina, UB, EUS, and IUS had
      been separately anesthetized, produced no change. CONCLUSION: Vaginal balloon
      distension appears to effect vesical relaxation and increased IUS tone. This
      seems to provide a mechanism to avoid urine leakage during coitus and to occur
      through a reflex we term 'vagino-urethrovesical reflex'.

PMID- 18066571
TI  - Gender differences in polysomnographic findings in Turkish patients with
      obstructive sleep apnea syndrome.
AB  - In this study, we evaluated the gender differences in body mass index (BMI), age
      and their effects on apnea-hypopnea index during total sleep time (AHI(TST)) in
      the Turkish population who were diagnosed with obstructive sleep apnea syndrome
      (OSAS) and compared them with data from the literature. A computerized database
      of 244 Turkish patients (194 males, 50 females) who had undergone overnight
      polysomnography (PSG) and diagnosed with OSAS at Bayindir Hospital sleep
      laboratory between October 2004 and January 2007 was reviewed. The male:female
      ratio of the patients was 3.88:1. Male patients were significantly younger
      compared to females (48.87 +/- 10.82 vs 52.94 +/- 12.14 years, respectively, P =
      0.003). The BMI and AHI(TST) were similar in male and female patients (BMI =
      29.52 +/- 4.63 vs 31.17 +/- 6.08 kg/m2, respectively, P = 0.083) (AHI(TST) =
      27.45 +/- 22.97 vs 24.77 +/- 23.83, respectively, P = 0.149). For the male and
      female groups, AHI(TST) increased as BMI increased (P = 0.03, 0.04). The median
      values of AHI(TST) in male group, for the normal, overweight and obese +
      pathological obese groups were 12.45, 20.20 and 23.50, respectively, whereas the
      median values of AHI(TST) in female group were 11.10, 10.95 and 26.20,
      respectively. In the normal and obese + pathological obese groups, there was no
      statistically significant difference according to gender, whereas in the
      overweight group, male patients had significantly higher AHI(TST) (P = 0.02).
      There was no statistically significant difference between the male and female
      patients regarding the severity of OSAS (P = 0.358). However, there was a male
      tendency to moderate and severe OSAS in the normal and overweight BMI groups. In
      Turkish patients with OSAS, there was no gender difference in BMI and AHI(TST)
      and female patients were significantly older than the males. The OSAS was
      diagnosed in men nearly four times more often than in women.

PMID- 18066572
TI  - The expression of somatostatin receptors 3, 4 and 5 in laryngeal pathology.
AB  - Conventional chemotherapy has no role to play in the curative treatment of
      laryngeal carcinoma, yet the mortality rate from advanced disease has improved
      little over the last 20 years. Somatostatin is a naturally occurring peptide,
      which exerts anti-proliferative and anti-angiogenic effects via 5 membrane-bound
      receptor subtypes (SSTRs 1-5). We have previously studied the expression of SSTRs
      1 and 2 and demonstrated loss of SSTR2 in laryngeal carcinoma. This study was
      therefore undertaken to study the expression of the remaining SSTR subtypes in
      laryngeal pathology. The expression of SSTRs 3, 4 and 5 was studied in benign
      (Reinke's oedema), pre-malignant and malignant laryngeal specimens using
      immunohistochemistry. There was very little expression of SSTR3, with low to
      moderate levels detected in just 1/6 (17%) benign and pre-malignant specimens and
      3/12 (25%) malignant laryngeal tumours. A variable degree of SSTR4 expression was
      detected across the three groups, with low to moderate levels in 3/6 (50%) benign
      specimens, compared to only 1/6 (17%) pre-malignant specimens but 8/12 (67%)
      malignant laryngeal tumours. The majority of all specimens, however, demonstrated
      moderate to high levels of expression of SSTR5. This receptor was detected in 4/6
      (67%) benign, all pre-malignant (100%) and 10/12 (83%) malignant cases. All the
      laryngeal carcinomas studied expressed either SSTR4 or SSTR5, with 60% expressing
      both, but very few expressing SSTR3. Somatostatin receptors warrant further
      investigation to determine whether they have a therapeutic role in carcinoma of
      the larynx.

PMID- 18066573
TI  - How I do it: securing tracheostomy tubes.
AB  - Securing a tracheostomy tube after insertion is essential to prevent accidental
      decannulation. Although this is uncommon, its associated mortality is high.
      Common practice involves suturing the lateral edges of the tube flanges to the
      skin. This can allow movement along the axis of the flanges. We describe a
      modification of the suture placement, which provides a more robust fixation.

PMID- 18066574
TI  - Gender differences in workers with identical repetitive industrial tasks:
      exposure and musculoskeletal disorders.
AB  - OBJECTIVES: For unknown reasons, females run a higher risk than males of work
      related musculoskeletal disorders. The aim of this study was to evaluate whether
      male and female workers, with identical repetitive work tasks, differ concerning
      risk of disorders, physical or psychosocial exposures. METHODS: Employees in two
      industries were studied; one rubber manufacturing and one mechanical assembly
      plant. These industries were selected since in both, large groups of males and
      females worked side by side performing identical repetitive work tasks. Physical
      exposure was measured by technical equipment. Postures and movements were
      registered by inclinometry for the head and upper arms, and by electrogoniometry
      for the wrists. Muscular activity (muscular rest and %max) was registered by
      surface electromyography for m. trapezius and the forearm extensors (18 males and
      19 females). Psychosocial work environment was evaluated by the demand-control
      support model (85 males and 138 females). Musculoskeletal disorders were assessed
      (105 males and 172 females), by interview (last 7-days complaints), and by
      physical examination (diagnoses). RESULTS: Concerning physical exposure, females
      showed higher muscular activity related to maximal voluntary contractions
      [(%MVE); m. trapezius: females 18 (SD 9.2), males 12 (SD 4.3); forearm extensors:
      females 39 (SD 11), males 27 (SD 10), right side, 90th percentile]. Working
      postures and movements were similar between genders. Also, concerning
      psychosocial work environment, no significant gender differences were found.
      Females had higher prevalences of disorders [complaints: age-adjusted prevalence
      odds ratio (POR) 2.3 (95% CI 1.3-3.8) for neck/shoulders, 2.4 (1.4-4.0) for
      elbows/hands; diagnoses: neck/shoulder 1.9 (1.1-3.6), elbows/hands 4.1 (1.2
      9.3)]. In 225 workers, PORs were adjusted for household work, personal recovery
      and exercise, which only slightly affected the risk estimates. CONCLUSION: In
      identical work tasks, females showed substantially higher muscular activity in
      relation to capacity, and higher prevalence of musculoskeletal disorders of the
      neck and upper extremity, than did males.

PMID- 18066575
TI  - Influence of glutathione-related genes on symptoms and immunologic markers among
      vulcanization workers in the southern Sweden rubber industries.
AB  - OBJECTIVE: The aim was to elucidate the role of genetic variants on symptoms of
      the eyes and airways, headache and nausea, as well as on immunologic markers,
      among vulcanization workers in the contemporary Swedish rubber industry.
      Polymorphisms in genes, which are involved in the defense against reactive oxygen
      species and metabolism of toxic substances present in the vulcanization fumes,
      were analyzed. METHODS: One hundred and forty-five exposed and 117 unexposed
      workers were included in the study. Medical and occupational histories were
      obtained in structured interviews. Symptoms were recorded and immunologic markers
      analyzed in blood. Polymorphisms in glutathione-related genes (glutamate cysteine
      ligase catalytic subunit (GCLC)-129, glutamate cysteine ligase modifier subunit
      (GCLM)-588, glutathione S-transferase alpha 1 (GSTA1)-52, GSTM1*O, GSTP1-105,
      GSTP1-114, and GSTT1*O) were analyzed by Taqman-based allelic discrimination and
      ordinary PCR. RESULTS: A protective effect of GSTA1-52 (G/A + A/A) genotype on
      symptoms and immunologic cells, in particular among exposed workers, was
      suggested. Exposed workers with GSTT1*O had increased risk of nosebleed compared
      to exposed workers with GSTT1*1. Exposed workers with GSTP1-105 (ile/val +
      val/val) had decreased levels of total immunoglobulin E (IgE) compared to exposed
      workers with GSTP1-105 ile/ile. GCLC-129 variant genotype demonstrated increased
      levels of immunologic cells among exposed workers, although statistical
      significance was not reached. CONCLUSION: Our data indicate that hereditary
      factors influence the susceptibility to symptoms and the immunologic response of
      workers in the rubber industry.

PMID- 18066576
TI  - Environmental and biological monitoring of antineoplastic drugs in four
      workplaces in a Swedish hospital.
AB  - OBJECTIVES: Exposure to antineoplastic drugs should be avoided due to the risk of
      getting adverse health effects. Antineoplastic drugs such as cyclophosphamide
      (CP) and ifosfamide (IF) are commonly used in medical attendance. In this study
      the variability of surface contamination of CP and IF was investigated by
      repeated wipe sampling over time in four workplaces in a university hospital. The
      surface contamination levels were also evaluated and health care workers were
      biologically monitored. METHODS: A hospital pharmacy, two oncology wards and one
      oncology outpatient department were selected. Between 10 and 13 different surface
      areas such as work areas, floors and handles were selected in each workplace and
      wiped between 7 and 8 times during 9 months. Pre- and post-shift urine samples
      were collected from the workers in the investigated workplaces. Analysis was
      performed by liquid chromatography combined with tandem mass spectrometry.
      RESULTS: Measurable amounts of CP and IF were detected on the majority of the
      sampled surfaces. The highest concentrations were found on the floors in the
      patient lavatories and utility rooms (up to 95 ng cm(-2)). In general, the
      surface contamination of CP and IF on floors did not vary much over time. Work
      areas and handles had larger variability. Neither CP nor IF were detected in any
      of the collected urine samples. CONCLUSIONS: The variability in surface
      contamination of CP and IF was rather low especially on floors. Higher
      concentrations of CP and IF were found on the floors compared with the work
      areas. The highest surface loads were found on floors (in patient lavatories and
      utility rooms) that were related to patient activities such as handling of
      patients' urine. Although high contaminations were found, the biological
      monitoring showed no uptake. Wipe sampling is a good method to improve the work
      practices.

PMID- 18066578
TI  - Effects of experimental muscle pain on shoulder-abduction force steadiness and
      muscle activity in healthy subjects.
AB  - We previously demonstrated that the steadiness of shoulder abduction is reduced
      in patients with subacromial impingement syndrome (SIS), which might be related
      to shoulder pain associated with the SIS. The aim of the present study was to
      examine the acute effects of experimental shoulder muscle pain on shoulder motor
      function in healthy subjects. The fluctuations in exerted force (force
      steadiness) and electromyographic (EMG) activity from eight shoulder muscles were
      determined during sub-maximal isometric and dynamic contractions with the
      shoulder abductors in nine healthy subjects (27.7 +/- 4.2 years, mean +/- 1 SD)
      before, during and after experimental pain induction. Experimental pain was
      induced by bolus injections of 6% hypertonic saline into the supraspinatus
      muscle. Experimental muscle pain reduced shoulder-abduction force steadiness on
      average by 21% during isometric contractions (P = 0.012) and tended to do so
      during concentric contractions (P = 0.083). Middle deltoid, and infraspinatus and
      lower trapezius muscle activity increased (3-5% EMG(max)) during isometric and
      concentric contractions, respectively (P < 0.05). Thus, experimental shoulder
      muscle pain reduced the steadiness of isometric shoulder abduction and caused
      small changes in the abduction activation strategy. The observed effects of
      experimental pain on shoulder motor function differed from that observed
      previously in patients with SIS and chronic pain during the same types of
      contractions. A possible explanation may be that, even though the adopted
      experimental pain-paradigm may reflect the SIS in terms of the painful
      structures, it might not reflect the adaptations in the central nervous system
      seen with chronic pain.

PMID- 18066577
TI  - Atopy, symptoms and indoor environmental perceptions, tear film stability, nasal
      patency and lavage biomarkers in university staff.
AB  - OBJECTIVE: Study associations between airway symptoms, complaints on
      environmental perceptions, atopy definitions and biomarkers including tear film
      stability (BUT), nasal patency and nasal lavage (NAL). Personal predictors
      (gender, age, smoking, infections) for the biomarkers as well as associations
      between the biomarkers were also assessed. METHODS: A cross-sectional study of
      173 employees in four university buildings, response rate 86%. Tear film break up
      time (BUT) was measured by a non-invasive method (NIBUT) and self-reported
      (SBUT). NAL-analysis included eosinophilic cationic protein (ECP),
      myeloperoxidase (MPO), lysozyme and albumin. Total serum IgE, and specific IgE
      using Phadiatop was measured. Data on subjective symptoms, environmental
      perceptions and background data were collected by use of a questionnaire.
      Multiple regression analyses were applied. RESULTS: Mean age was 43 years, 21%
      had weekly ocular, 21% nasal, and 17% laryngeal symptoms. Women had more
      complaints on environmental perceptions, shorter BUT and less nasal patency.
      Neither atopy (Phadiatop) nor Total IgE or allergy in the family, but asthma and
      hay fever was associated with mucosal symptoms or perceptions. Subjects with
      positive Phadiatop had higher levels of all NAL-biomarkers. Those with ocular
      symptoms had shorter BUT. Nasal symptoms were related to respiratory infections
      and laryngeal symptoms to NAL-lysozyme. Perceiving dry air was associated with
      lower BUT and reduced nasal volume difference before and after decongestion.
      Older subjects had greater nasal patency, and less atopy. All NAL-biomarkers were
      positively correlated. Higher lysozyme level was associated with less nasal
      patency and greater nasal decongestion. CONCLUSIONS: BUT and NAL-lysozyme was
      associated with ocular, nasal, laryngeal symptoms and indoor environmental
      perceptions. Ever having had asthma and ever having had hay fever were predictors
      for symptoms and perceived air quality, respectively. Phadiatop, Total IgE,
      familiar allergy and ever eczema were not associated to symptoms or perceived
      environments. Age, gender and Phadiatop were main predictors for ocular and nasal
      biomarkers.

PMID- 18066579
TI  - Changes of elastic properties of central arteries during acute static exercise
      and lower body negative pressure.
AB  - The aim of this investigation was to determine the acute effects of isometric
      fatiguing handgrip (IFHG) and lower body negative pressure (LBNP) on indices of
      central arterial stiffness. Thirteen subjects were studied. Renal blood velocity
      (Duplex Ultrasound) and blood pressure (Finapres) were monitored during IFHG and
      LBNP at -30 and -50 mmHg. Radial pulse-wave forms were recorded by applanation
      tonometry. Central aortic waveforms and other hemodynamic parameters were
      assessed using the Sphygmocor software. Renal vascular resistance index (RVRI;
      mean BP/renal blood velocity) was used as index of sympathetic nervous system
      (SNS) engagement. RVRI increased during both IFHG and LBNP indicating that SNS
      was engaged; however, BP increased only during the IFHG. Pulse-wave analysis
      showed that during the IFHG protocol the transit time of the pulse wave decreased
      and the peripheral pulse pressure/nonaugmented central pulse pressure ratio
      increased from baseline. Both of these measurements suggest an increase in
      central large artery stiffness. During LBNP no changes in the indices of central
      stiffness were noted, in spite of a similar level of sympathetic system
      engagement. Heart rate increased during both protocols, whereas augmentation
      index increased during the IFHG protocol and decreased during the LBNP. Our major
      conclusion was that blood pressure rather than sympathetic activity seems to play
      the major role in modulating the elastic properties of the central arteries. The
      decrease in augmentation index during the LBNP protocol can be attributed to the
      increased heart rate, given that there is a negative correlation between these
      two parameters.

PMID- 18066580
TI  - Sympathetic cardiovascular control during orthostatic stress and isometric
      exercise in adolescent chronic fatigue syndrome.
AB  - The chronic fatigue syndrome (CFS) has been shown to be associated with
      orthostatic intolerance and cardiovascular dysregulation. We investigated the
      cardiovascular responses to combined orthostatic stress and isometric exercise in
      adolescents with CFS. We included a consecutive sample of 15 adolescents 12-18
      years old with CFS diagnosed according to a thorough and standardized set of
      investigations, and a volunteer sample of 56 healthy control subjects of equal
      sex and age distribution. Heart rate, systolic, mean and diastolic blood
      pressure, stroke index, and total peripheral resistance index were non-invasively
      recorded during lower body negative pressure (LBNP) combined with two consecutive
      periods of handgrip. In addition, we measured baseline plasma catecholamines, and
      recorded symptoms. At rest, CFS patients had higher heart rate, diastolic blood
      pressure, plasma norepinephrine (P < 0.01), mean blood pressure and plasma
      epinephrine (P < 0.05) than controls. During LBNP, CFS patients had a greater
      increase in heart rate, diastolic blood pressure, mean blood pressure (P < 0.05)
      and total peripheral resistance index (n.s.) than controls. During handgrip, CFS
      patients had a smaller increase in heart rate, diastolic blood pressure (P <
      0.05), mean blood pressure and total peripheral resistance index (n.s.) than
      controls. Our results indicate that adolescents with CFS have increased
      sympathetic activity at rest with exaggerated cardiovascular response to
      orthostatic stress, but attenuated cardiovascular response when performing
      isometric exercise during orthostatic stress. This suggests that CFS might be
      causally related to sympathetic dysfunction.

PMID- 18066581
TI  - Occupational exposure to cold thermal environments: a field study in Portugal.
AB  - The present work is essentially dedicated to the study of cold thermal
      environments. The analysis includes 32 industrial units from 6 activity sectors
      and the measurements were carried out in 101 workplaces. Different environmental
      conditions were identified and a clear relationship with the different types of
      workplaces was established. The work environments were thus allocated to three
      typical exposure categories corresponding to freezing and refrigerating cold
      stores and free-running or controlled air temperature manufacturing workplaces.
      In order to characterize the level of cold exposure, the method proposed by
      ISO/TR 11079, Technical Report, 1st edn, International Organization for
      Standardization, Geneva (1993) was adopted. The results for each activity sector
      demonstrate that a significant percentage of workers are repeatedly exposed to
      extreme conditions with insufficient clothing insulation. A value between 20 and
      40% corresponds to the most critical situation, where the selected clothing
      ensemble does not provide adequate insulation (I (clr) < IREQ (min)). The ideal
      scenario, represented by I (clr) values between IREQ (min) and IREQ (neutral),
      shows the lowest percentages with an overall result of only 10%. When all the
      sectors are considered together, from a total of 3,667 workers, about one-third
      (1,151) are exposed to the cold. Among the workplaces under analysis, 14 are
      characterized by a continuous exposure greater than the DLE (neutral). Those who
      work under such conditions, on average, have a time shift 60 min longer than the
      calculated DLE value.

PMID- 18066582
TI  - Parametric spectral analysis of nonstationary fluctuations of excitatory synaptic
      currents.
AB  - We assessed on Monte-Carlo simulated excitatory post-synaptic currents the
      ability of autoregressive (AR)-model fitting to evaluate their fluctuations. AR
      model fitting consists of a linear filter describing the process that generates
      the fluctuations when driven with a white noise. Its fluctuations provide a
      filtered version of the signal and have a spectral density depending on the
      properties of the linear filter. When the spectra of the non-stationary
      fluctuations of excitatory post-synaptic currents were estimated by fitting AR
      models to the segments of current fluctuations, assumed to be stationary and
      independent, the parameter and spectral estimates were scattered. The scatter was
      much reduced if the time-variant AR-models were fitted using stochastic adaptive
      estimators (Kalman, recursive least squares and least mean squares). The ability
      of time-variant AR-models to accurately fit the current fluctuations was
      monitored by comparing the fluctuations with predicted fluctuations, and by
      evaluating the model-learning rate. The median frequency of current fluctuations,
      which could be rapidly tracked and estimated from the individual quantal events
      (either Monte-Carlo simulated or recorded from pyramidal neurons of rat
      hippocampus), rose during the rise phase, before declining to a lower steady
      state level during the decay phase of quantal event, whereas the variance showed
      a broad peak. The closing rate of AMPA channels directly affects the steady-state
      median frequency, whereas the transient peak can be modulated by a variety of
      factors-number of molecules released, ability of glutamate molecules to re-enter
      the synaptic cleft, diffusion constant of glutamate in the cleft and opening rate
      of AMPA channels. In each case, the effect on the amplitude and decay time of
      mEPSCs and on the current fluctuations differs. Each factor thus leaves its own
      kinetic fingerprint arguing that the contribution of such factors can be inferred
      from the combined kinetic properties of individual mEPSCs.

PMID- 18066583
TI  - Through a barn owl's eyes: interactions between scene content and visual
      attention.
AB  - In this study we investigated visual attention properties of freely behaving barn
      owls, using a miniature wireless camera attached to their heads. The tubular eye
      structure of barn owls makes them ideal subjects for this research since it
      limits their eye movements. Video sequences recorded from the owl's point of view
      capture part of the visual scene as seen by the owl. Automated analysis of video
      sequences revealed that during an active search task, owls repeatedly and
      consistently direct their gaze in a way that brings objects of interest to a
      specific retinal location (retinal fixation area). Using a projective model that
      captures the geometry between the eye and the camera, we recovered the
      corresponding location in the recorded images (image fixation area). Recording in
      various types of environments (aviary, office, outdoors) revealed significant
      statistical differences of low level image properties at the image fixation area
      compared to values extracted at random image patches. These differences are in
      agreement with results obtained in primates in similar studies. To investigate
      the role of saliency and its contribution to drawing the owl's attention, we used
      a popular bottom-up computational model. Saliency values at the image fixation
      area were typically greater than at random patches, yet were only 20% out of the
      maximal saliency value, suggesting a top-down modulation of gaze control.

PMID- 18066584
TI  - Lost needle: a simple search device for the operating room's floor.
AB  - BACKGROUND/AIMS: Needle-stick injuries provide a substantial threat in regard to
      health of victims and may cause extra costs to health systems. MATERIALS AND
      METHODS: We report on simple strategies to prevent a needle-stick injury by
      analysing search devices which can detect a lost needle. RESULTS: A magnetic
      device enables the surgeon as well as other staff members working in the
      operating room to locate a lost needle on the floor rapidly. For search in body
      cavities, X-ray examination is recommended. CONCLUSION: With simple methods, a
      lost needle can be found easily to prevent any harm for others in the future.

PMID- 18066587
TI  - On the interplay between familiarity and emotional expression in face perception.
AB  - Traditional models of face perception (e.g. Bruce and Young 1986) stress
      independent routes for processing identity and emotional expression. We
      investigated the interplay between familiarity and emotional expression by
      systematically varying both factors. In contrast to earlier studies which used
      binary forced-choice decisions, participants had to judge the familiarity of the
      presented face and the emotional hedonic valence and emotional arousal of its
      expressed emotion (angry, happy or neutral), using rating scales. The results
      demonstrated symmetric, strong interactions between familiarity and expressed
      emotion. Thus, this study supports more recent models of face perception (Haxby
      et al. 2000) that were mostly based on brain imaging data. These data together
      with our behavioural results emphasize the interaction of emotional expression
      and personal identity and support approaches that propose a relative segregation
      of these processes, rather than completely independent coding (Calder and Young
      2005).

PMID- 18066586
TI  - Novel rice OsSIPK is a multiple stress responsive MAPK family member showing
      rhythmic expression at mRNA level.
AB  - We report isolation and transcriptional profiling of rice (Oryza sativa L.)
      mitogen-activated protein kinase (MAPK), OsSIPK (salicylic acid-induced protein
      kinase). OsSIPK gene is located on chromosome 6 most probably existing as a
      single copy in the rice genome, and encodes 398 amino acid polypeptide having the
      MAPK family signature and phosphorylation activation motif TEY. Steady state mRNA
      analyses of OsSIPK showed weak constitutive expression in leaves of 2-week-old
      rice seedlings. A time course (30-120 min) experiment using a variety of
      elicitors and stresses revealed that the OsSIPK mRNA is strongly induced by
      jasmonic acid (JA), salicylic acid (SA), ethephon, abscisic acid, cycloheximide
      (CHX), JA/SA + CHX, cantharidin, okadaic acid, hydrogen peroxide, chitosan,
      sodium chloride, and cold stress (12 degrees C), but not with wounding by cut,
      gaseous pollutants ozone, and sulfur dioxide, high temperature, ultraviolet C
      irradiation, sucrose, and drought. Its transcription was also found to be tissue
      specifically regulated, and followed a rhythmic dark induction in leaves.
      Finally, we showed that the OsSIPK protein is localized to the nucleus. From
      these results, OsSIPK can be implicated in diverse stimuli-responsive signaling
      cascades and transcription of certain genes.

PMID- 18066585
TI  - The role of actin remodeling in the trafficking of intracellular vesicles,
      transporters, and channels: focusing on aquaporin-2.
AB  - Trafficking of the intracellular vesicles and membrane protein incorporated in
      the vesicles is essential for a variety of basic biological processes. Growing
      evidence has highlighted the importance of the actin cytoskeleton in the
      trafficking of synaptic vesicles, secretory granules, transporters, and channels
      including aquaporin. These trafficking processes require actin remodeling, which
      is spatiotemporally regulated. Recent researches have come to focus on the
      motility mechanism of the translocation. In this review, we describe the role of
      actin at each step of intracellular reservation, exocytosis, docking, fusion with
      the plasma membrane, and endocytosis, focusing on aquaporin-2 trafficking.

PMID- 18066588
TI  - Proteomic identification of heat shock protein 27 as a differentiation and
      prognostic marker in neuroblastoma but not in Ewing's sarcoma.
AB  - Neuroblastoma (NB) and Ewing's sarcoma (ES) cell lines were analysed by two
      dimensional gel electrophoresis (2-DE) searching for new diagnostic/prognostic
      markers. Protein expression profiles displayed a high degree of similarity with
      the exception of marked heat shock protein (HSP) 27 and less marked HSP60 and
      HSP70 family up-modulations in NB cells. HSP27, which showed peculiar variability
      in different NB cell preparations, responded to all trans-retinoic acid treatment
      in NB cells but not in ES cells at gene and protein expression levels.
      Immunohistochemistry studies showed different behaviours of HSP27 and HSP70
      expression in NB and ES biopsies. HSP27 was less expressed, whereas HSP70 was
      more expressed in the immature areas of NB. HSP27 expression showed positive and
      statistically significant correlation with favourable prognosis, and HSP27
      expression also negatively correlated with increasing aggressiveness of
      histological type. In ES, both chaperones were expressed without characteristic
      patterns. Our results suggest that HSP27, after further clinical validations,
      could be used as a marker of neuronal differentiation in vivo for the assessment
      of the biological behaviour of NB and for the risk stratification of patients.

PMID- 18066589
TI  - Mature cystic teratoma of the ovary with male accessory sexual glands including
      seminal vesicles, prostatic tissue, and bulbo-urethral glands: a case report.
AB  - We present an extremely rare case of a benign cystic ovarian teratoma with
      structures of male accessory sexual glands. The patient was a 30-year-old woman.
      A unilocular cystic tumor, measuring 5 cm in the largest diameter, was found in
      her right ovary and was removed. The teratoma contained epidermis, skin
      appendages, respiratory and intestinal epithelia, cartilage, muscle, and nervous
      and connective tissue. In addition to these histologically mature tissues, there
      were nodules with prostatic acini, prostate duct-like structures strongly
      positive for prostate-specific antigen and acid prostatic phosphatase, structures
      resembling Cowper's glands, and seminal vesicles surrounded by fibromuscular
      stroma. To our knowledge, this is the first case in the English literature
      describing seminal vesicles associated with prostatic tissue and bulbo-urethral
      glands in a mature ovarian teratoma.

PMID- 18066590
TI  - Renal oncocytoma with and without intravascular extension into the branches of
      renal vein have the same morphological, immunohistochemical, and genetic
      features.
AB  - We attempted to investigate the clinicopathological correlation of renal
      oncocytoma (RO) with renal vein extension. We identified seven ROs with extension
      into the branches of renal vein. The age of seven patients ranged from 61 to 82
      years. Five cases were identified incidentally; two patients had gross hematuria.
      After surgery, all patients were alive and free of tumors with follow-up of 1 to
      5 years (mean = 3.6). Oncocytomas measured from 2.2 to 7.5 cm. Renal vein
      extension was grossly suspected in five of seven cases and histologically
      confirmed in all seven cases. Tumor cells were positive for cytokeratins,
      mitochondrial-antigen (MIA), epithelial membrane antigen (EMA), and parvalbumin;
      five of seven tumors were focally positive for CD117. Ultrastructurally, the
      cytoplasm was packed by mitochondria. Molecular genetic analysis did not detect
      abnormal numbers of chromosomes 1, 2, 6, 7, 10, 17, and XY by fluorescence in
      situ hybridization, loss of heterozygosity on 3p and mutation of von Hippel
      Lindau gene in all cases. Array comparative genomic hybridization analysis of two
      cases did not show any major genetic changes. Our conclusions are as follows: (1)
      renal oncocytomas may have intravascular extension to the branches of the renal
      vein; (2) renal oncocytomas with intravascular extension to the branches of the
      renal vein have the same morphological, immunohistochemical, and cytogenetic
      findings as have their counterparts without evidence of intravascular invasion;
      (3) the absence of metastases suggests an overall benign behavior of this tumor,
      but this has to be substantiated by further studies with a long-term follow-up;
      and (4) in a renal tumor with granular cytoplasm showing renal vein extension, it
      is necessary to carefully exclude renal cell carcinomas such as chromophobe RCC,
      oncocytic variant of papillary RCC, and granular variant of clear cell RCC.

PMID- 18066591
TI  - Pigmented lipofibromatosis in unusual location: case report and review of the
      literature.

PMID- 18066592
TI  - C-kit protein expression correlated with activating mutations in KIT gene in oral
      mucosal melanoma.
AB  - C-kit is a trans-membrane receptor tyrosine kinase (RTK) encoded by the proto
      oncogene KIT located at 4q11-12. Gain-of-function mutations arising to c-kit
      activation independent of its ligand were observed in various tumors related to
      germ cells, mast cells, and interstitial cells of Cajal. C-kit also participates
      in melanocyte development; hence, its involvement in oral mucosal melanoma (OMM)
      tumorigenesis was investigated. Immunohistochemistry and mutation analysis were
      performed using 18 cases of human primary OMM. Results revealed 16 cases positive
      to c-kit protein. Atypical melanocytes expressed c-kit. All in situ components
      expressed c-kit, but only four cases exhibited intense expression in the invasive
      component. Missense mutations were observed in four cases, and two of those
      correlated with increased protein expression. C-kit expression in atypical
      melanocytes suggests the role of c-kit in the early stage of OMM tumorigenesis. C
      kit protein expression correlated with activating mutations indicating the
      pertinent role of the proto-oncogene KIT in the tumorigenesis of OMM.

PMID- 18066593
TI  - Expression of CCN3 protein in human Wilms' tumors: immunohistochemical detection
      of CCN3 variants using domain-specific antibodies.
AB  - We aimed to detect truncated CCN3 protein variants in formalin-fixed paraffin
      embedded samples of eight Wilms' tumors using anti-K19M and novel domain-specific
      antibodies, anti-NH2, anti-NH3, anti-NH4, and anti-NH5 raised against C-terminal
      (CT) domain and modules 1, 2, 3, and 4 of the CCN3 protein, respectively. In
      Wilms' tumors, all the domain antibodies except anti-NH4 exhibited both nuclear
      and cytoplasmic staining in blastema as well as primitive tubules. NH4 was
      detected only in the cytoplasm of tumor cells. Normal fetal kidneys revealed
      mainly cytoplasmic immunoreactivity for all antibodies in tubules and glomeruli,
      except for K19 and NH5, which showed some nuclear staining. Our data suggest
      expression of a truncated nuclear CCN3 variant lacking the thrombospondin type-1
      like domain and cytoplasmic full-length CCN3 protein in Wilms' tumor cells. In
      addition, normal fetal kidneys express mainly full-length protein mostly
      localized to cytoplasm. Truncated CCN3 protein in Wilms' tumor cells may provide
      evidence for its tumorigenic role in these tumors. Uniform NH5 staining compared
      to variable expression of K19M indicates that using NH5 is a better approach for
      detecting the CT domain of CCN3 protein in archival specimens. Thus, the domain
      specific antibodies represent valuable tools for detecting CCN3 protein variants
      in normal and neoplastic kidneys.

PMID- 18066594
TI  - The phosphorylation profile of protein kinase A substrates is modulated during
      Varicella-zoster virus infection.
AB  - The cAMP-dependent protein kinase A (PKA) is a key enzyme for many cellular
      mechanisms. In this study, we investigated the importance of this kinase for the
      replication of the alphaherpesvirus Varicella-zoster virus (VZV). We report that
      the expression of the catalytic subunit of PKA was strongly increased at the
      beginning of the viral cycle. The presence of a peptide inhibitor of PKA had no
      consequence on viral replication in a melanoma cell line whereas in fibroblasts,
      it resulted in a drastic decrease of replication. An overall analysis of PKA
      substrates phosphorylation patterns during VZV replication showed that the
      phosphorylation of PKA substrates was modulated. These results were completed by
      investigating the accumulation and phosphorylation patterns of the PKA target
      cAMP response element binding protein (CREB). This transcription factor remained
      available throughout the VZV replication, but its phosphorylation decreased in
      the early phase of infection before it rose later on. These results indicate that
      the PKA signalling plays a cell-type dependent role for VZV replication and that
      the infection resulted in a regulated CREB-dependent gene expression.

PMID- 18066595
TI  - Post varicella hepatic actinomycosis in a 5-year-old girl mimicking acute
      abdomen.
AB  - Actinomycosis is an indolent, slowly progressive infection caused by gram
      positive, anaerobic or microaerophilic bacteria. Hepatic involvement is rare and
      generally secondary to abdominal or thoracic actinomycosis. Hepatic actinomycosis
      in children may mimic a wide variety of diseases and thus make the diagnosis much
      more challenging. Here, we report a 5-year-old girl with apparently primary
      hepatic actinomycosis mimicking acute abdomen 2 weeks after varicella. The
      diagnosis was made by ultrasonic guided fine needle aspiration biopsy of a
      hypoechoic lesion of 3.5 cm diameter in the liver showing sulfur granules
      surrounded by neutrophils. Hepatic actinomycosis should be taken into account
      when evaluating acute abdomen symptoms in children.

PMID- 18066596
TI  - Synergistic antitumor effect of CXCL10 with hyperthermia.
AB  - PURPOSE: IFN-inducible protein 10 (IP-10)/CXCL10 (CXC chemokine ligand 10) has
      been described as an antiangiogenic chemokine and displays a potent antitumor
      activity in vivo. In the present study, we try to investigate whether the
      combination therapy of hyperthermia, a physical antiangiogenic modality, with
      CXCL10 would completely eradicate the established solid tumors. METHODS:
      Immunocompetent BALB/c mice bearing Meth A fibrosarcoma were established. Mice
      were treated with either CXCL10 at 25 microg/kg once a day for 20 days,
      hyperthermia was given twice (at 42 degrees C for 1 h, on day 6 and 12 after the
      initiation of CXCL10), or together. Tumor volume and survival time were observed.
      The microvessel density was determined by CD31 immunofluorescence. Histologic
      analysis and assessment of apoptotic cells were also conducted in tumor tissues.
      RESULTS: The results showed that CXCL10 and hyperthermia inhibited the growth of
      Meth A fibrosarcoma and interestingly, the combination therapy enhanced the
      antiangiogenic effects and completely eradicated the established solid tumors.
      Histological examination revealed that CXCL10 + hyperthermia led to increased
      induction of apoptosis, tumor necrosis, and elevated lymphocyte infiltration
      compared with the controls. Moreover, the tumor eradicated animals developed a
      protective T-cell-dependent antitumor memory response against Meth A tumor cells
      rechallenge. CONCLUSIONS: Our finding is that the combination therapy can achieve
      a synergistic antitumor efficacy, supporting the idea that the combination of two
      antiangiogenic agents may lead to improved clinical outcome. These findings could
      open new perspectives in clinical antitumor therapy.

PMID- 18066597
TI  - Blood coagulation in falciparum malaria--a review.
AB  - Falciparum malaria infection influences blood coagulation by various interacting
      pathobiological mechanisms, the most important being the overwhelming response of
      the host to sepsis resulting in a cytokine storm. In addition, the parasite
      infects the red cells leading to changes in the red cell phospholipid composition
      which supports blood coagulation. Red cells infected with Plasmodium falciparum
      also adhere to deeper tissue capillary endothelium leading to profound damage to
      endothelial cells leading to further activation. This results in widespread
      consumption of platelets and activation of blood coagulation which at times
      culminates in a clinically and pathologically detectable disseminated
      intravascular coagulation (DIC). Monocyte-macrophage system also gets activated
      in this infection compounding the hypercoagulable state. Heavy parasitaemia
      leading to occlusion of hepatic microcirculation leads to abnormalities in
      synthesis and secretion of coagulation factors and their inhibitors. Drugs used
      in the treatment for falciparum malaria can cause thrombocytopaenia, bone marrow
      suppression and haemolytic anaemia, all of which can interfere indirectly with
      blood coagulation. Microparticle formation from platelets, red cells and
      macrophages also causes widespread activation of blood coagulation, and this
      recently observed mechanism is the focus of intense research in many other
      inflammatory and neoplastic conditions where there is activation of blood
      coagulation system. Thus, in severe falciparum malaria, there is activation of
      blood coagulation system along with thrombocytopaenia, even before widespread DIC
      and coagulation failure occur.

PMID- 18066598
TI  - Discrimination of Babesia major and Babesia ovata based on ITS1-5.8S-ITS2 region
      sequences of rRNA gene.
AB  - Babesia ovata and Babesia major are two newly identified large Babesia species
      infective to cattle in China. There is a demand for specific tools for
      discrimination between the two species due to the confusion of their
      classification based on traditionally classification methods, such as tick
      vector, morphology, and pathogenicity. In this study, the internal transcribed
      spacers (ITS including ITS1, 5.8S coding region and ITS2) were originated from
      four isolates of B. ovata and one of B. major from different geographic regions
      of China, and a phylogenetic tree was inferred. It was demonstrated that all of
      the four isolates of B. ovata were grouped into one cluster, while B. major
      isolate was placed in another. The sequence percent identity showed that B. ovata
      isolates had the minimum 85.5% identity, whereas B. major showed only the maximum
      46.6% identity to the four B. ovata isolates. In addition, the identity of ITS1
      and ITS2 of these Babesia isolates was discussed. The findings implied that the
      four B. ovata isolates have a quite close relationship, whereas the B. major
      isolate showed far relationship with all of these B. ovata isolates. This finding
      may lead to the conclusion that there is actual existence of two large Babesia
      infective to cattle in China, one is B. ovata and the another is B. major.

PMID- 18066600
TI  - Diagnosis of Sarcocystis cruzi, Neospora caninum, and Toxoplasma gondii
      infections in cattle.
AB  - The aim of the study was to diagnose Sarcocystis sp. infections in cattle and to
      detect coinfections by Toxoplasma gondii and/or Neospora caninum. Blood,
      diaphragm, esophagus, and myocardium from 90 beef cattle from Argentina were
      collected. Histopathological, immunohistochemical, polymerase chain reaction
      assays, and direct microscopical examination were carried out. Sarcocysts from
      myocardium were measured and counted. Indirect fluorescent antibody test (IFAT)
      for the three protozoans was performed. Sarcocystis cruzi sarcocysts were found
      in 100% of myocardium samples. Sarcocysts per gram ranged from 8 to 380 with
      higher values found in adult cattle (p < 0.001). T. gondii and N. caninum were
      not detected by immunohistochemistry. T. gondii DNA was found in myocardium of
      2/20 seropositive animals, while N. caninum DNA was not found. Antibodies against
      S. cruzi were detected in all samples, those against N. caninum in 73% and
      against T. gondii in 91% of the samples (IFAT titer > or =25). It is concluded
      that serology by IFAT is a suitable method to diagnose these protozoan infections
      due to its specific IgG detection; therefore, IFAT may be a useful tool to
      evaluate the impact of each protozoan infection in coinfected animals.

PMID- 18066599
TI  - Trypanocidal activity of extracts and compounds from the stem bark of Anogeissus
      leiocarpus and Terminalia avicennoides.
AB  - The antitrypanosomal activity of methanolic extracts of Anogeissus leiocarpus and
      Terminalia avicennoides were evaluated in vitro against four strains of
      Trypanosoma species with minimum inhibitory concentration (MIC) value range of
      12.5-50 mg/ml. Successive fractionations of the two plant extracts in water,
      butanol and ethyl acetate gave a range of activity (MIC, 20 to > or =50
      microg/ml). Activity-guided and chromatographic analysis of butanolic fractions
      on Sephadex LH-20 column followed by high-performance liquid chromatography,
      nuclear magnetic resonance analysis and both ultraviolet and thin layer
      chromatography revealed hydrolysable tannins with a range of activity (MIC, 7.5
      27.5 microg/ml or 14-91 microM). Effect of the compounds on fibroblasts did not
      reveal serious toxicity at moderate concentration but is concentration dependent.

PMID- 18066601
TI  - Fine mapping of familial prostate cancer families narrows the interval for a
      susceptibility locus on chromosome 22q12.3 to 1.36 Mb.
AB  - Genetic studies suggest that hereditary prostate cancer is a genetically
      heterogeneous disease with multiple contributing loci. Studies of high-risk
      prostate cancer families selected for aggressive disease, analysis of large
      multigenerational families, and a meta-analysis from the International Consortium
      for Prostate Cancer Genetics (ICPCG), all highlight chromosome 22q12.3 as a
      susceptibility locus with strong statistical significance. Recently, two
      publications have narrowed the 22q12.3 locus to a 2.18 Mb interval using 54 high
      risk families from the ICPCG collaboration, as defined by three recombination
      events on either side of the locus. In this paper, we present the results from
      fine mapping studies at 22q12.3 using both haplotype and recombination data from
      42 high-risk families contributed from the Mayo Clinic and the Prostate Cancer
      Genetic Research Study (PROGRESS) mapping studies. No clear consensus interval is
      present when all families are used. However, in the subset of 14 families with
      >/=5 affected men per family, a 2.53-Mb shared consensus segment that overlaps
      with the previously published interval is identified. Combining these results
      with data from the earlier ICPCG study reduces the three-recombination interval
      at 22q12.3 to approximately 1.36 Mb.

PMID- 18066602
TI  - Exotic earthworm effects on hardwood forest floor, nutrient availability and
      native plants: a mesocosm study.
AB  - A greenhouse mesocosm experiment, representing earthworm-free North American Acer
      dominated forest floor and soil conditions, was used to examine the individual
      and combined effects of initial invasion by three European earthworm species
      (Dendrobaena octaedra, Lumbricus rubellus and Lumbricus terrestris) on the forest
      floor and upper soil horizons, N and P availability, and the mortality and
      biomass of four native understory plant species (Acer saccharum, Aquilegia
      canadensis, Aralia racemosa, and Carex pensylvanica). All the three earthworm
      species combined caused larger impacts on most variables measured than any single
      earthworm species. These included loss of O horizon mass, decreased thickness of
      the O horizon and increased thickness of the A horizon, and higher availability
      of N and P. The latter finding differs from field reports where nutrients were
      less available after invasion, and probably represents an initial transient
      increase in nutrient supply as earthworms consume and incorporate the O horizon
      into the A horizon. Earthworms also increased mortality of plants and decreased
      total mesocosm plant biomass, but here the impact of all the three earthworm
      species was no greater than that of L. terrestris and/or L. rubellus alone. This
      study corroborates field studies that European earthworm invasions alter North
      American forest ecosystem processes by initiating a cascade of impacts on plant
      community composition and soil properties.

PMID- 18066603
TI  - The reproductive assurance benefit of selfing: importance of flower size and
      population size.
AB  - Autonomous selfing can provide reproductive assurance (RA) for flowering plants
      that are unattractive to pollinators or in environments that are pollen limited.
      Pollen limitation may result from the breakdown of once-continuous habitat into
      smaller, more isolated patches (habitat fragmentation) if fragmentation
      negatively impacts pollinator populations. Here we quantify the levels of pollen
      limitation and RA among large and small populations of Collinsia parviflora, a
      wildflower with inter-population variation in flower size. We found that none of
      the populations were pollen limited, as pollen-supplemented and intact flowers
      did not differ in seed production. There was a significant effect of flower size
      on RA; intact flowers (can self) produced significantly more seeds than
      emasculated flowers (require pollen delivery) in small-flowered plants but not
      large-flowered plants. Population size nested within flower size did not
      significantly affect RA, but there was a large difference between our two
      replicate populations for large-flowered, small populations and small-flowered,
      large populations that appears related to a more variable pollination environment
      under these conditions. In fact, levels of RA were strongly negatively correlated
      with rates of pollinator visitation, whereby infrequent visitation by pollinators
      yielded high levels of RA via autonomous selfing, but there was no benefit of
      autonomous selfing when visitation rates were high. These results suggest that
      autonomous selfing may be adaptive in fragmented habitats or other ecological
      circumstances that affect pollinator visitation rates.

PMID- 18066604
TI  - [A survey of labour pain management in Germany].
AB  - BACKGROUND: In a survey of German hospitals with obstetric units, data on
      anaesthesia and analgesia in obstetric pain management were collected. METHODS:
      At each of 918 hospitals with obstetric units, the head of the anaesthetic
      department received a questionnaire on obstetric pain management. RESULTS: The
      response rate was 47.1%. On average, there were 748+/-407 (median 663;1st/3rd
      quartiles 309/1,303) births per year and hospital, 69.4% with spontaneous vaginal
      delivery. Opioids were the systemic analgesics most frequently administered in
      the delivery rooms. Epidural analgesia (EA) was given to 17.5+/-12.6% of the
      parturients. The number of deliveries per annum had a significant influence on
      the frequency of EA (<500 deliveries/year: 12.7%, 500-1000/year: 18.6%,
      >1,000/year: 21.6%). The preferred local anaesthetics were ropivacaine und
      bupivacaine. When an opioid was given this was almost always sufentanil. In 16%
      of the responding hospitals adrenaline was added to the epidural test bolus.
      CONCLUSION: EA is the mainstream method of relieving labour pains in almost all
      German hospitals, but is used significantly more often in hospitals with rather
      high numbers of yearly deliveries than in hospitals in which there are few
      deliveries per year.

PMID- 18066605
TI  - [Postoperative pain after ambulatory surgery].
AB  - BACKGROUND: Outpatient surgeons were surveyed about the quality of postoperative
      pain therapy after outpatient interventions. PATIENTS AND METHODS: Of 2,317
      outpatient surgeons who received a questionnaire by mail, 419 responded. The
      return rate was 18.1%. The questionnaire collected data on the operative
      procedures and methods of anesthesia from 2004 and the analgesics, which were
      applied in the immediate postoperative period and at home. Methods and contents
      of quality control were registered. RESULTS: The respondents indicated that the
      person responsible for the pain therapy was the surgeon in 74% of the practices,
      the anesthesiologist in 16%, and both in 10%. The drugs used in the practice
      were: novaminsulfone (34%), NSAIDs (28%), and opioids (36%). The drugs used for
      at-home care were: NSAIDs (58%), opioids (43%), novaminsulfone (32%), and mixed
      analgesics (28%). No analgesics were given by 6%, and 21% prescribed a
      supplementary antiemetic. Routine pain measurement was performed with pain scales
      in only 11% of the practices; among the certified practices, 48% performed pain
      measurement for quality control. Ninety-five percent of the surgeons were
      satisfied with the pain therapy. CONCLUSION: This survey shows that the
      guidelines for acute pain therapy (http://www.awmf.de ) are only partially
      implemented.

PMID- 18066606
TI  - Tricholoma matsutake 1-Ocen-3-ol and methyl cinnamate repel mycophagous
      Proisotoma minuta (Collembola: Insecta).
AB  - Two major volatiles produced by the mycelia and fruiting bodies of Tricholoma
      matsutake (1-octen-3-ol and methyl cinnamate) repel a mycophagous collembolan,
      Proisotoma minuta. Aggregation of the collembolans on their diet was
      significantly inhibited by exposure to 1 ppm methyl cinnamate or 10 to 100 ppm 1
      octen-3-ol. The aggregation activity decreased dose-dependently upon exposure to
      1-octen-3-ol at concentrations higher than 0.01 ppm. Aggregation in the presence
      of methyl cinnamate exhibited three phases: no significant effect at
      concentrations ranging from 0.001 to 0.1 ppm, significant inhibition from 1 to
      100 ppm, and strong inhibition at 1,000 ppm. These results may explain why
      certain collembolan species do not prefer T. matsutake fruiting bodies.

PMID- 18066607
TI  - Social mobbing calls in common marmosets (Callithrix jacchus): effects of
      experience and associated cortisol levels.
AB  - We compared the mobbing response to model snakes of two groups of captive-born
      common marmosets (Callithrix jacchus) differing in genetic relatedness, age and
      past experience. Mobbing vocalisations (tsik calls), other mobbing behaviour and
      attention to the stimulus were recorded for 2 min. intervals pre-exposure, during
      exposure to various stimuli and post-exposure. Marmosets in one group were
      vocally reactive to all stimuli, although more so to one particular stimulus
      resembling rearing snakes and modified images of it, whereas the marmosets in a
      younger and genetically unrelated group attended to the stimuli but made very few
      mobbing calls. The parent stock of the first group had suffered stress in early
      life and had developed a phobic response to a specific stimulus, which they had
      transmitted to their offspring. A third group, matching the older group in age
      range but genetically unrelated, was also found to be unresponsive to the
      stimulus that elicited the strongest response in the first group. Cortisol levels
      in samples of hair were assayed and a significant negative correlation was found
      between the number of tsik calls made during presentation of the stimuli and the
      cortisol level, showing that mobbing behaviour/behavioural reactivity is
      associated with low levels of physiological stress.

PMID- 18066609
TI  - Comment on Kanis et al.: the use of clinical risk factors enhances the
      performance of BMD in the prediction of hip and osteoporotic fractures in men and
      women.

PMID- 18066610
TI  - A high activity index of stearoyl-CoA desaturase is associated with increased
      risk of fracture in men.
AB  - The activity index of stearoyl-CoA desaturase (SCD), a key enzyme in lipogenesis,
      was associated with increased risk of fracture in a longitudinal population-based
      cohort of men. This indicates that elevated levels of endogenous lipogenesis
      increase the risk of fracture and suggest a role for saturated fat in the
      pathogenesis of osteoporosis. INTRODUCTION: Osteoblasts and marrow adipocytes are
      derived from a common mesenchymal progenitor, and experimental studies have
      indicated that increased adipogenesis can occur at the expense of osteoblasts,
      leading to bone loss. Stearoyl-CoA desaturase (SCD) converts saturated to
      monounsaturated fatty acids and is a key enzyme in lipogenesis. METHODS: Analysis
      was performed in a population-based, longitudinal cohort study of men (n = 2009).
      A product-to-precursor index (palmitoleic acid/palmitic acid) was used to
      estimate SCD activity in fasting serum analyzed in samples obtained at enrollment
      at age 50 years. Fractures were documented in 422 men during 35 years of follow
      up. Cox regression analysis was used to determine the risk of fracture according
      to SCD activity index. RESULTS: The risk of fracture was highest among men with
      the highest levels of SCD activity index. Multivariable analysis of the risk of
      fracture in the highest quintile as compared to the lowest one showed that the
      rate ratio was 1.71 (95% CI 1.26-2.33) for any fracture, with an estimated
      population attributable risk of 15%. The risk was further increased within the
      highest quintile. CONCLUSIONS: Our results indicate that elevated levels of
      endogenous lipogenesis increase the risk of fracture and suggest a role for
      saturated fat in the pathogenesis of osteoporosis.

PMID- 18066611
TI  - Statin treatment for rheumatoid arthritis: a promising novel indication.
AB  - The results of several cross-sectional trials suggest that patients with
      rheumatoid arthritis (RA) have increased vascular risk and cardiovascular
      mortality. It was demonstrated that inflammation plays a pivotal role in the
      pathogenesis of both RA and atherosclerosis. This association may explain the
      high incidence of cardiovascular disease in RA patients. A number of recent
      studies show that routine statin use in patients with RA offers considerable
      advantages. Statin treatment has been supported to exert a beneficial effect on
      disease activity, swollen joint count, endothelial dysfunction, and arterial
      stiffness in RA patients. These improvements are coupled with a mild to moderate
      improvement in plasma markers of inflammation, such as C-reactive protein and
      erythrocyte sedimentation rate. Statins have a satisfactory safety profile with
      relatively few adverse effects. In the absence of side effects and
      contraindications, it may be reasonable to consider statin use in selected cases,
      particularly in patients with a long history of active RA who are at increased
      cardiovascular risk.

PMID- 18066612
TI  - Is anticoagulation unnecessary in Behcet's disease with deep venous thrombosis?

PMID- 18066613
TI  - Photodynamic therapy using talaporfin sodium for synovial membrane from
      rheumatoid arthritis patients and collagen-induced arthritis rats.
AB  - We investigated the efficacy of photodynamic therapy (PDT) using talaporfin
      sodium as a new method of synovectomy for rheumatoid arthritis (RA). We first
      used RA synovial membrane (RASM) for in vitro and in vivo study. The RASM was
      obtained from patients with RA during total knee replacement. In the in vitro
      study, RA fibroblast-like synoviocytes (RASCs) obtained from the RASM were
      examined by fluorescent microscopy to measure the intracellular localization of
      talaporfin sodium. The cells were then subjected to PDT, and their viability was
      examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulphophenyl)-2H-tetrazolium inner salt assay. In the in vivo assay, RASM was
      obtained as described above, grafted onto severe combined immunodeficiency (SCID)
      mice and subjected to PDT. The damaged area of RASM was evaluated histologically
      at 1 day after PDT. Next, we performed a separate experiment using rats with
      collagen-induced arthritis (CIA). After intra-articular injection of talaporfin
      sodium, the concentration of talaporfin sodium accumulated in the CIA synovial
      membrane (CIASM) was compared with that in cartilage, periarticular muscle, and
      skin. We then performed PDT with intra-articular injection of talaporfin sodium
      and intra-articular irradiation. The damaged area of the CIASM was measured at 1
      day after the PDT, and the articular histological and radiological changes of the
      ankle were observed at 56 days after the PDT. In RASM, talaporfin sodium
      accumulated in lysosomes in vitro, and the phototoxicity to RASCs in vitro and to
      RASM grafted onto SCID mice in vivo depended on the concentration of talaporfin
      sodium and the laser energy. In CIA rats, there was a greater accumulation of
      talaporfin sodium in the CIASM than in normal tissue. The CIASM was selectively
      damaged at 1 day after the PDT, and the bone and cartilage destruction were
      ameliorated at 56 days after the PDT. In conclusion, PDT using talaporfin sodium
      might be a new method for synovectomy in patients with RA.

PMID- 18066615
TI  - Patient-specific surgical simulation.
AB  - Technological innovations of the twentieth century have provided medicine and
      surgery with new tools for education and therapy definition. Thus, by combining
      Medical Imaging and Virtual Reality, patient-specific applications providing
      preoperative surgical simulation have become possible.

PMID- 18066614
TI  - Macrophage and T-lymphocyte infiltrates in human peritoneal adhesions indicate a
      chronic inflammatory disease.
AB  - BACKGROUND: Peritoneal adhesions are common and lead to significant clinical
      morbidity and mortality. Besides various individual factors, notably the
      inflammatory response to peritoneal defects affects adhesion formation. The aim
      of this study was to investigate whether there is inflammatory activity even in
      persistent adhesions. METHODS: Tissue specimens of 40 patients suffering
      peritoneal adhesions were prospectively collected. Expression profiles of seven
      parameters as potential mediators in cellular immune response, cell
      differentiation, and wound healing were analyzed (macrophages [CD68], B
      lymphocytes [CD20] and T-lymphocytes [CD45], cyclo-oxygenase-2 [COX-2], Notch-3,
      beta-catenin, and c-myc). Furthermore, clinical details and co-morbidities were
      recorded. RESULTS: Infiltrates of mononuclear round cells were found in all
      adhesion specimens irrespective of the maturity. Immunohistochemical analysis
      identified mononuclear round cells as macrophages (CD68) and as T-lymphocytes
      (CD45). Expression of CD68 was significantly elevated in adhesion tissue with an
      age<12 months. Positive expression of CD45, COX-2, Notch-3, beta-catenin, and c
      myc, was observed even in long-lasting adhesions. CONCLUSIONS: A persistent
      inflammatory process has to be considered, even in mature adhesions. Macrophages
      may play an important role in triggering adhesions, whereas T-cells and the Notch
      3/beta-catenin complex signaling pathway may play a crucial role in maintaining
      adhesions. These findings indicate that adhesions should not be regarded simply
      as an adynamic result of an operative trauma but rather may be grasped as a
      permanent process in remodeled tissue.

PMID- 18066616
TI  - Long-term results after dissection of positive thoracic lymph nodes in patients
      with esophageal squamous cell carcinoma.
AB  - BACKGROUND: Although thoracic lymph node metastasis in patients with thoracic
      esophageal squamous cell carcinoma (SCC) has been reported to be a negative risk
      factor for long-term survival, only a few studies have evaluated the
      clinicopathologic difference between the impact of metastasis to the
      paraesophageal lymph nodes and to the nonparaesophageal lymph nodes. The purpose
      of this study was to evaluate surgical outcome after the clearance of metastatic
      thoracic lymph nodes. METHODS: Retrospectively reviewed were 164 consecutive
      patients with thoracic esophageal SCC who had not had preoperative treatment and
      underwent surgery from 1980 to 2005 and were found to have thoracic lymph node
      metastases. Of these patients, 83 underwent surgery from 1980 to 1994 and 81 from
      1995 to 2005. Univariate and multivariate analyses were performed to evaluate the
      impact of nonparaesophageal lymph node metastasis on survival. RESULTS:
      Univariate analysis revealed that T3/T4 tumors and the presence of
      nonparaesophageal node metastases were associated with only a 20% overall five
      year survival rate. The overall five-year survival for the most recent period was
      significantly better than for the former period (42% vs. 13%, p<0.01). Based on a
      multivariate analysis of prognostic impact of each nonparaesophageal node, the
      presence of metastatic subcarinal and/or posterior mediastinal nodes was an
      independent risk factor for reduced survival. CONCLUSION: Surgical outcome for
      patients with thoracic esophageal cancer and metastatic thoracic lymph nodes has
      improved during the last 25 years. Although postoperative chemotherapy might
      improve survival, the presence of T3/T4 tumors and/or metastatic
      nonparaesophageal nodes were unfavorable factors for survival.

PMID- 18066617
TI  - Surgical thrombectomy for thrombosed dialysis grafts: comparison of adjunctive
      treatments.
AB  - BACKGROUND: Vascular surgeons often encounter dialysis graft failure in
      hemodialysis patients during their daily practice. Despite advances in
      percutaneous treatment, there remains a role for surgical thrombectomy of
      thrombosed dialysis grafts. This study was designed to investigate the long-term
      outcome of dialysis graft thrombectomy and to examine the indications for and
      effectiveness of therapies adjuvant to Fogarty thrombectomy. METHODS: Surgical
      outcomes of 590 consecutive dialysis graft thrombectomies performed between 2001
      and 2003 were retrospectively reviewed. The 590 cases were classified into four
      groups based on the procedure performed adjuvant to Fogarty thrombectomy: group
      A, surgical thrombectomy by Fogarty thrombectomy catheter alone; group B,
      thrombectomy plus intraoperative angioplasty of graft outlet; group C,
      thrombectomy plus sequential balloon angioplasty in subsequent intervention;
      group D, thrombectomy plus graft outlet surgical revision. Age, gender, co
      morbidity, and primary patency of grafts were reviewed and analyzed. RESULT: The
      four groups exhibited similar demographic features and comorbidities (p>0.05).
      Mean primary patency in the four groups was 1.99+/-4.02, 7.21+/-7.61, 8.35+/
      9.53, and 7.26+/-6.99 (months), respectively. Survival curves for each group were
      determined by Kaplan-Meier methods. Primary patency in group A was statistically
      inferior to all of the other three groups, whereas groups B, C, and D did not
      significantly differ with regard to graft patency. CONCLUSIONS: Surgical
      thrombectomy alone is inadequate for treating a thrombosed dialysis graft. The
      underlying graft outlet stricture requires direct surgical revision or balloon
      angioplasty during surgery or intervention in the angiography suite to ensure
      long-term patency of the graft.

PMID- 18066618
TI  - Pneumoperitoneum following percutaneous biliary intervention: not necessarily a
      cause for alarm.
AB  - Percutaneous transhepatic cholangiography (PTC) is a well-established technique
      for assessing and treating obstructive jaundice. Plastic and self-expanding metal
      stents can be deployed as an alternative when ERCP is not feasible or hilar
      strictures require an antegrade approach. Complication rates of percutaneous
      procedures are low, and are usually related to bile leakage or hemorrhage;
      pneumoperitoneum following PTC is rare and is usually taken to indicate bowel
      perforation. We describe two cases of pneumoperitoneum without peritonitis
      following PTC and stenting, both of which resolved spontaneously with
      conservative management. The literature is reviewed and possible causes
      discussed.

PMID- 18066619
TI  - Carbohydrate and ethane release with Erwinia carotovora subspecies betavasculorum
      -induced necrosis.
AB  - Erwinia carotovora subspecies betavasculorum, also known as E. betavasculorum and
      Pectobacterium betavasculorum, is a soil bacterium that has the capacity to cause
      root rot necrosis of sugarbeets. The qualitatively different pathogenicity
      exhibited by the virulent E. carotovora strain and two avirulent strains, a
      Citrobacter sp. and an Enterobacter cloacae, was examined using digital analysis
      of photographic evidence of necrosis as well as for carbohydrate, ethane, and
      ethylene release compared with uninoculated potato tuber slices. Visual scoring
      of necrosis was superior to digital analysis of photographs. The release of
      carbohydrates and ethane from potato tuber slices inoculated with the soft rot
      necrosis-causing Erwinia was significantly greater than that of potato tuber
      slices that had not been inoculated or that had been inoculated with the
      nonpathogenic E. cloacae and Citrobacter sp. strains. Interestingly, ethylene
      production from potato slices left uninoculated or inoculated with the
      nonpathogenic Citrobacter strain was 5- to 10-fold higher than with potato slices
      inoculated with the pathogenic Erwinia strain. These findings suggest that (1)
      carbohydrate release might be a useful measure of the degree of pathogenesis, or
      relative virulence; and that (2) bacterial suppression of ethylene formation may
      be a critical step in root rot disease formation.

PMID- 18066620
TI  - Characterization of the ETnII-alpha endogenous retroviral element in the BALB/cJ
      Zhx2 ( Afr1 ) allele.
AB  - Integration of mouse endogenous retroviral (MERV) elements is responsible for an
      estimated 10% of spontaneous mutations that have been characterized in the
      laboratory mouse. We recently identified a MERV integration in the first intron
      of the Zinc fingers and homeoboxes 2 (Zhx2) gene in BALB/cJ mice, resulting in
      reduced Zhx2 expression. This integration is found in BALB/cJ but not in other
      BALB/c substrains, indicating that it occurred after these substrains separated
      in the late 1930s. We have characterized this MERV element and show here that it
      belongs to the ETnII-alpha class of elements. Our analysis reveals that the Zhx2
      ETn element lacks a 69-bp sequence compared to most other ETn elements which may
      be due to recombination between two identical 13-bp elements. Three mature Zhx2
      transcripts are found in the liver of BALB/cJ mice. The major transcript is
      spliced from Zhx2 exon 1 to the 5' ETn LTR and is polyadenylated at the 3' LTR.
      Of the two less abundant transcripts, one is identical to the wild-type
      transcript, whereas the second contains 183 bp of ETn sequence spliced between
      Zhx2 exons 1 and 2. We have also sequenced and analyzed products from the fas (
      lpr ) ETn found in MRL/lpr mice and show that it belongs to the ETnII-beta class
      of elements.

PMID- 18066621
TI  - Basic mechanisms of cough: current understanding and remaining questions.
AB  - Considerable effort in many laboratories has gone into describing the afferent
      nerve subtypes that initiate cough, and the ionic mechanisms the activation and
      modulation of these nerves. In this brief overview, we have attempted to
      summarize some of what is understood in these areas. In addition, we have tried
      to highlight many of the important basic questions that remain to be answered.

PMID- 18066622
TI  - Metabolic and biochemical responses of the healthy human lung to nonthoracic
      surgery.
AB  - The objective of this study was to evaluate and assign numbers to biochemical or
      cellular entities in lung-healthy patients that change immediately postsurgery
      compared with the same parameters immediately presurgery, with the hypothesis
      that biochemical markers with significant change could be the basis of tests to
      predict postoperative respiratory complications. Thirty lung-healthy adults who
      were to undergo elective surgical procedures requiring general anesthesia
      participated. The population included sequential persons that met inclusion
      criteria and gave consent. At intubation and before surgery, a bonchoalveolar
      lavage (BAL) was performed. Before extubation but after completion of surgical
      procedures, a second 100-ml BAL was performed in the contralateral lung. Serum
      from both time periods was also collected. Total cell counts were elevated
      postsurgery in smokers and subjects claiming childhood but not current asthma,
      who also showed increased postsurgical BAL IL-1 but not increased TNFalpha. LDH
      and its isoenzymes, measured in both BAL and serum, showed no correlation with
      time on surgical ventilation, average FiO2, or average peak pressure during
      surgical ventilation. BAL LDH isoenzyme 4 showed a significant elevation pattern
      pre-to-post surgery when the entire subject population was considered
      irrespective of surgery type or time on ventilation. Presurgery versus
      postsurgery variation was best measured in BAL rather than in serum. The
      pulmonary, biochemical, and cellular parameters measured in the pre- and
      postsurgical BALs of lung-healthy subjects undergoing nonthoracic surgery show
      subtle modulations of pulmonary defense markers, defined by significantly
      increased proinflammatory cytokines and cell counts postsurgery compared to the
      same patient presurgery.

PMID- 18066623
TI  - The economic impact of obstructive sleep apnea.
AB  - Untreated obstructive sleep apnea (OSA) increases healthcare utilization and is
      associated with reduced work performance and occupational injuries. The economic
      burden related to untreated OSA is substantial, accounting for billions of
      dollars per year. Furthermore, therapy of OSA is an extremely cost-efficient use
      of healthcare resources, comparing highly favorably with other commonly funded
      medical therapies. Governments, transportation agencies, industry, and insurance
      companies need to be better informed concerning the economic impact of untreated
      OSA and the benefits of therapy.

PMID- 18066624
TI  - Discrimination of Schroeder-phase harmonic complexes by normal-hearing and
      cochlear-implant listeners.
AB  - The temporal fine structure (TFS) of sound contributes significantly to the
      perception of music and speech in noise. The evaluation of new strategies to
      improve TFS delivery in cochlear implants (CIs) relies upon the assessment of
      fine structure encoding. Most modern CI sound processing schemes do not encode
      within-channel TFS per se, but some TFS information is delivered through temporal
      envelope cues across multiple channels. Positive and negative Schroeder-phase
      harmonic complexes differ primarily in acoustic TFS and provide a potential test
      of TFS discrimination ability in CI users for current and future processing
      strategies. The ability to discriminate Schroeder-phase stimuli was evaluated in
      24 CI users and 7 normal-hearing listeners at four fundamental frequencies: 50,
      100, 200, and 400 Hz. The dependent variables were percent correct at each
      fundamental frequency, average score across all fundamental frequencies, and a
      maximum-likelihood-predicted threshold fundamental frequency for 75% correct. CI
      listeners scored better than chance for all fundamental frequencies tested. The
      50-Hz, average, and predicted threshold scores correlated significantly with
      consonant-nucleus-consonant word scores. The 200-Hz score correlated with a
      measure of speech perception in speech-shaped noise. Pitch-direction sensitivity
      is predicted jointly by the 400-Hz Schroeder score and a spectral ripple
      discrimination task. The results demonstrate that the Schroeder test is a
      potentially useful measure of clinically relevant temporal processing abilities
      in CI users.

PMID- 18066625
TI  - Automated multidetector row CT dataset segmentation with an interactive watershed
      transform (IWT) algorithm: Part 2. Body CT angiographic and orthopedic
      applications.
AB  - The preceding manuscript describes the principles behind the Interactive
      Watershed Transform (IWT) segmentation tool. The purpose of this manuscript is to
      illustrate the clinical utility of this editing technique for body multidetector
      row computed tomography (MDCT) imaging. A series of cases demonstrates clinical
      applications where automated segmentation of skeletal structures with IWT is most
      useful. Both CT angiography and orthopedic applications are presented.

PMID- 18066626
TI  - Invasive anal squamous-cell carcinoma in the HIV-positive patient: outcome in the
      era of highly active antiretroviral therapy.
AB  - INTRODUCTION: The incidence of invasive anal squamous-cell carcinoma in patients
      with HIV is increasing. We report the outcome after combined chemoradiotherapy
      for anal squamous-cell carcinoma in HIV-infected individuals. METHODS: Thirty-two
      HIV-positive patients treated at the St. Vincent's Cancer Care Center for anal
      squamous-cell carcinoma from 1997 through mid 2005 were reviewed retrospectively.
      All patients also received highly active antiretroviral therapy. Treatment
      consisted of radiotherapy concurrent with 5-fluorouracil and mitomycin C in most
      patients. Overall survival, anal cancer-specific survival, local recurrence, and
      toxicity were assessed. RESULTS: Median time from completion of radiotherapy to
      last follow-up of surviving patients was 35 months. Five-year locoregional
      relapse, anal cancer-specific survival, and overall survival were 16 , 75, and 65
      percent, respectively. In multivariate analysis, locoregional recurrence, cancer
      specific survival, and overall survival were all significantly associated with
      tumor size. Overall survival was independently associated with high viral load
      and low CD4 count. Acute toxicity included: Grade 3 skin in 25 percent of
      patients, Grade 3 diarrhea: 28 percent, and Grade 3 or 4 hematologic toxicity in
      21 and 48 percent, respectively. More than two-thirds of patients required
      radiotherapy interruption. There was no negative impact of chemoradiotherapy on
      viral load. CONCLUSIONS: Outcome after chemoradiotherapy for HIV-related anal
      squamous-cell carcinoma in the era of highly active antiretroviral therapy is
      comparable to outcome in patients without HIV. However, significant toxicity is
      seen with standard treatment regimens. Earlier diagnosis and risk-adapted therapy
      could lead to improved survival and decreased treatment-related morbidity.

PMID- 18066627
TI  - When sentinel lymph node is intramammary.
AB  - INTRODUCTION: Sentinel lymph node biopsy is an accepted standard of care for
      staging the axilla in patients with early-stage breast cancer. Little attention
      has been placed to the presence of intramammary sentinel lymph nodes (intraMSLNs)
      on preoperative lymphoscintigraphy. METHODS: Between December 2001 and September
      2006, in 9632 breast cancer patients with clinically uninvolved axillary nodes,
      lymphoscintigraphy was performed at the European Institute of Oncology (EIO). An
      axillary SLN (axSLN) was identified in 99.4% of cases. An intraMSLN was
      identified in association with the axillary sentinel lymph node in 22 patients
      (0.2%). In 15 cases both the axSLN and the intraMSLN were excised. RESULTS: The
      intraMSLN was positive in six patients (micrometastatic in three cases). The
      axSLNs were negative in all 15 cases. Two patients with positive intraMSLNs and
      one patient with a negative intraMSLN underwent axillary dissection; all three
      cases had negative axillary nodes. At a median follow-up of 24 months, no
      locoregional or systemic recurrences were observed. CONCLUSIONS: Positive
      intraMSLNs can improve disease staging but do not necessarily portend axillary
      lymph node metastasis. When intraMSLNs and axSLNs are present, we advocate biopsy
      of both sites and that management of the axilla should rely on axSLN status. In
      cases with intraMSLNs as the only draining site on lymphoscintigraphy, decisions
      on axillary management should be made on individualized basis.

PMID- 18066628
TI  - Sudden shifts in ecological systems: intermittency and transients in the coupled
      Ricker population model.
AB  - Many real ecological systems show sudden changes in behavior, phenomena sometimes
      categorized as regime shifts in the literature. The relative importance of
      exogenous versus endogenous forces producing regime shifts is an important
      question. These forces' role in generating variability over time in ecological
      systems has been explored using tools from dynamical systems. We use similar
      ideas to look at transients in simple ecological models as a way of understanding
      regime shifts. Based in part on the theory of crises, we carefully analyze a
      simple two patch spatial model and begin to understand from a mathematical point
      of view what produces transient behavior in ecological systems. In particular,
      since the tools are essentially qualitative, we are able to suggest that
      transient behavior should be ubiquitous in systems with overcompensatory local
      dynamics, and thus should be typical of many ecological systems.

PMID- 18066629
TI  - Elastohydrodynamics of the eyelid wiper.
AB  - This paper presents an elastohydrodynamic model of the human eyelid wiper.
      Standard lubrication theory is applied to the fluid layer between the eyelid
      wiper and ocular surface. The role of the lubrication film is to reduce the shear
      stresses by preventing solid to solid contact between the eyelid wiper and ocular
      surface. For the lubrication film to be effective, it is required that the
      orientation of the eyelid wiper changes between the opening and closing phases of
      a blink. In order to model this, the hydrodynamic model is coupled with an
      elastic mattress model for the soft tissue of the eyelid wiper and ocular
      surface. This leads to a one-dimensional non-linear partial differential equation
      governing the fluid pressure in the lubrication film. In order to solve the
      differential equation, a loading condition or constraint equation must be
      specified. The resulting system is then solved numerically. The model allows
      predictions of the tear film flux from under the upper eyelid, as well as normal
      and shear stresses acting on the ocular surface. These factors are important in
      relation to dry eye syndrome, deformation of the cornea and contact lens design.
      It is found that the pressure and shear stress under the eyelid act across a
      length of approximately 0.1 mm which is consistent with clinical observations. It
      order to achieve a flow of tears from under the upper eyelid during a blink, the
      model requires that the normal force the eyelid applies to the ocular surface
      during the closing phase of the blink is significantly higher than during the
      opening phase of the blink.

PMID- 18066630
TI  - Treatment intensification and blood glucose control among hospitalized diabetic
      patients.
AB  - BACKGROUND: Hyperglycemia is common among diabetic inpatients, and has been
      linked to adverse outcomes. However, antihyperglycemic treatment is seldom
      intensified in noncritical care patients, and the relationship between
      intensification frequency and glucose control is poorly understood. We evaluated
      the relationship between treatment intensification and changes in blood glucose
      in hospitalized diabetic patients. DESIGN: We retrospectively analyzed 3,613
      hospitalized diabetic patients who were admitted to the hospital between January
      2003 and August 2004, were not hospitalized in an ICU, were not prescribed IV
      insulin or total parenteral nutrition (TPN), had a length of stay of at least 3
      days, and had at least one point-of-care blood glucose measurement. A linear
      model was used to assess the relationship between intensification of
      antihyperglycemic medications and the average daily change in point-of-care
      glucose measurements. RESULTS: Hyperglycemia (>180 mg/dL) was documented at least
      once for 82.5% of patient admissions. Antihyperglycemic treatment was intensified
      for 22.0% of days with hyperglycemia. Intensifications of scheduled and sliding
      scale insulin, but not oral medications, were associated with a 11.1 mg/dL (p <
      0.0001) and 12.2 mg/dL (p < 0.0001) reduction in the average daily glucose,
      respectively. Hypoglycemia (<50 mg/dL) was documented on 2.2% of days after
      antihyperglycemic treatment intensification. CONCLUSION: In this cohort, lack of
      treatment intensification in response to inpatient hyperglycemia was common.
      Antihyperglycemic treatment intensification was strongly associated with decrease
      in average daily glucose, while hypoglycemia was uncommon. This suggests that
      increasing the frequency of treatment intensifications could lead to improved
      glycemic control in inpatients with diabetes.

PMID- 18066631
TI  - Patient expectations as predictors of outcome in patients with acute low back
      pain.
AB  - BACKGROUND: Few studies have evaluated the association between patient
      expectations for recovery and clinical outcomes, and no study has evaluated
      whether asking patients to choose their therapy modifies such an association.
      OBJECTIVE: To evaluate the association between patients' expectations and
      functional recovery in patients with acute low back pain (LBP), and to determine
      whether that association is affected by giving patients choice of therapy. DESIGN
      AND PARTICIPANTS: A secondary analysis of a randomized controlled trial comparing
      usual care alone to usual care plus choice of chiropractic, acupuncture, or
      massage in 444 adults with acute LBP, lasting less than 21 days. MEASUREMENTS AND
      MAIN RESULTS: Primary outcome was functional disability (Roland score) at 5 and
      12 weeks. Patients' general expectations for improvement were associated with
      improvement in functional status (beta = 0.96, 95% CI = 0.56, 1.36). A 1-point
      increase in general expectations was associated with a 0.96-point improvement in
      Roland score. The association of expectation with outcome was 2-3 times greater
      in the usual care group than the choice group. However, these differences did not
      reach statistical significance. CONCLUSIONS: In patients with acute LBP, higher
      expectations for recovery are associated with greater functional improvement.
      Eliciting patient expectations for improvement may be a simple way to identify
      patients with the highest (or lowest) likelihood of experiencing functional
      improvement. Incorporating questions about patient expectations in future trials
      may clarify the role of this important correlate of clinical outcomes.

PMID- 18066632
TI  - Renal cell carcinoma metastatic to the duodenum: treatment by classic
      pancreaticoduodenectomy and review of the literature.
AB  - Renal cell cancer (RCC) most commonly metastasizes to the lungs, bones, liver,
      renal fossa, and brain, although metastases can occur elsewhere. RCC metastatic
      to the duodenum is especially rare, with only a small number of cases reported in
      the literature. Herein, we describe a case of an 86-year-old woman with a history
      of RCC treated by radical nephrectomy 13 years previously. The patient presented
      with duodenal obstruction and anemia from a solitary duodenal mass invading into
      the pancreas and was treated via classic pancreaticoduodenectomy. Preoperative
      imaging and intra-operative assessment showed no evidence of other disease.
      Pathology confirmed metastatic RCC without lymph node involvement. Our case
      report and review of the English language literature underscore the rarity of
      this entity and support aggressive surgical treatment in such patients.

PMID- 18066633
TI  - The loop stoma bridge--a new technique.
AB  - BACKGROUND: Conventionally, supporting rods made of glass, plastic, or similar
      material have been used for 1 week to 10 days for loop stomas to prevent
      retraction. However, this is associated with difficulty in applying the stomal
      appliance till removal of the rod resulting in leakage of fecal matter. METHODS:
      A closed suction drain tube of 16 or 18 F placed in the subcutaneous tissue with
      the help of a trocar is used as a bridge. The points of entry and exit of the
      tube are just beyond the circumference of the flange. RESULTS: Apart from
      discomfort and pain in 5 patients, no major complications were encountered in the
      33 patients studied. CONCLUSION: The method described is safe, cheap, and easily
      performed by junior surgical resident with low morbidity. The colostomy flange
      can be applied immediately without leakage.

PMID- 18066634
TI  - Bariatric surgery: the past, present, and future.
AB  - BACKGROUND: Our objective is to review the history and development of different
      procedures of bariatric surgery, along with a summary of the most commonly
      performed bariatric procedures today and a look on the future trends in the field
      of bariatric surgery. METHODS: Review of the available English language
      literature concerning bariatric surgery. RESULTS: The literature review included
      articles that have information about the history of bariatric surgery, different
      techniques used for each procedure, and the outcome of each procedure.
      CONCLUSIONS: Bariatric surgery is a dynamic field. Experts are continuously
      searching for an ideal, minimally invasive procedure that is both safe and
      effective.

PMID- 18066635
TI  - Tissue distribution of cynomolgus adeno-associated viruses AAV10, AAV11, and
      AAVcy.7 in naturally infected monkeys.
AB  - Adeno-associated virus (AAV) is used in gene-therapy studies, but its tissue
      distribution is unknown in natural infection. We examined cynomolgus AAVs
      (previously isolated AAV10 and AAV11 and novel AAVcy.7) for their tissue
      distribution in 14 cynomolgi by type-specific PCR. We found AAV10, AAV11, and
      AAVcy.7 in 6, 10, and 14 monkeys, respectively, and two or three types in 11
      monkeys, showing that these AAVs are widespread in the monkeys. We detected AAV
      at a higher level mainly in the lymphatic tissues and ileum, which suggests that
      AAV may invade the host through Peyer's patches in the ileum and infect immune
      cells.

PMID- 18066636
TI  - Characterization and susceptibility to antiviral agents of herpes simplex virus
      type 1 containing a unique thymidine kinase gene with an amber codon between the
      first and the second initiation codons.
AB  - A herpes simplex virus type 1 (HSV-1) containing a thymidine (TK) gene with an
      amber mutation at the 8th position counted from the first AUG codon was isolated
      from a child with acute gingivostomatitis. The virus was predicted to express a
      mutant viral translated from the 2nd AUG codon at the 46th amino acid position
      and consisting of 331 amino acids. The virus was as sensitive to acyclovir (ACV),
      5-bromovinyl-2'-deoxyuridine (BVdU), 1-beta-D-arabinofuranosyl-(E)-5-(2
      bromovinyl)uracil (BVaraU), and 1-beta-D-arabinofuranosylthymine (araT) as a wild
      type HSV-1. The mutant TK showed the same level of TK activity as the wild-type
      TK at reaction temperatures of 34 degrees C, 37 degrees C and 39 degrees C. ACV,
      BVdU, BVaraU, and araT inhibited the replication of the TK-deficient and drug
      resistant HSV-1 and HSV-2 in 293T cells in which the mutant TK was expressed to
      the same extent as in cells in which intact HSV-1-TK was expressed, whereas BVdU
      and BVaraU inhibited the replication of these viruses less strongly in cells in
      which HSV-2-TK was expressed. It can be concluded that the mutant HSV-1 exists in
      nature as a variant and possesses the necessary phosphorylation activities to
      form ACV-monophosphate from ACV, to form BVdU-diphosphate through BVdU
      monophosphate from BVdU, and to form BVaraU-diphosphate through BVaraU
      monophosphate from BVaraU. These results indicate that the mutant HSV-1-TK with a
      deletion of the first 45 amino acid residues is phenotypically the same as that
      of wild-type HSV-1-TK in terms of the phosphorylation activity of TK-associated
      anti-herpes virus drugs.

PMID- 18066637
TI  - Functional analysis of brome mosaic virus coat protein RNA-interacting domains.
AB  - The coat proteins (CP) of cowpea chlorotic mottle (CCMV) and brome mosaic virus
      (BMV), two members of the genus Bromovirus, share 70% identity at the amino acid
      (aa) level and contain four highly conserved regions, identified as putative RNA
      interacting domains (RIDs). To assess the contribution of the conserved aa
      sequence within each RID and the structural features contained therein toward
      virion assembly and RNA packaging, we engineered a set of fourteen independent
      mutations (deletions and substitutions) encompassing all four RIDs. The effect of
      each mutation on viral biology, pathogenesis, and RNA packaging was analyzed in
      whole-plant infection assays. Among the four RIDs, two mutations engineered into
      the N-proximal domain (RID I) and two of the four mutations engineered into the C
      proximal domain (RID IV) proved to be more debilitating (compared to wild-type)
      while only selected regions in the central domains (RID II or III) showed a
      detectable effect. Neutral effects were observed when aa residues that are
      predicted to affect calcium binding were mutated. To further analyze the
      importance of N and C terminal interactions leading to virus assembly and RNA
      packaging, four CP hybrids were constructed by precisely exchanging either the N
      terminal 77 or the C-terminal 113/112aa between BMV and CCMV. Despite the fact
      that the CP composition of the hybrid viruses is distinct from either of the
      parents, the symptom phenotype in Chenopodium quinoa, migration pattern of CP in
      Western blots and virion mobility in agarose gels was indistinguishable from the
      respective parent providing the genetic background. Collectively, the data
      provide insight for assessing the relative importance of each RID during genome
      packaging and in molecular processes regulating the overall architecture of the
      assembled virions.

PMID- 18066638
TI  - The 61st Annual Scientific Meeting of The Japanese Association for Thoracic
      Surgery Fukuoka, October 12-15, 2008. Editorial.

PMID- 18066639
TI  - An attempt to analyze the relation between hospital surgical volume and clinical
      outcome.
AB  - OBJECTIVES: The aim of this study was to investigate the relation between
      hospital volume and clinical surgical outcome for 10 cardiac, lung, and
      esophageal surgical procedures. METHODS: The Committee for Scientific Affairs of
      the Japanese Association for Thoracic Surgery collected the pooled data on
      cardiac, lung, and esophageal surgical procedures between 2000 and 2004 from the
      annual reports. The relation between operative mortality (30-day or in-hospital
      mortality) and hospital volume was analyzed using a logistic regression model.
      The surgical procedures studied were surgery for acquired cardiac diseases
      [coronary artery bypass grafting (CABG), valve procedures, acute type A
      dissection surgery], total CABG (elective + emergency), elective CABG, emergency
      CABG, single-valve surgery, acute type A dissection surgery, open heart surgery
      for the newborn, open heart surgery for the infants, lung cancer surgery, and
      esophageal cancer surgery. The data used in this study were not risk-adjusted.
      RESULTS: The data on the relation between hospital volume and operative mortality
      generally tended to show an inverse correlation for all 10 cardiac, lung, and
      esophageal surgical procedures; that is, the higher was the volume the lower was
      the mortality. However, wide variations in operative mortality were noted among
      the very-low-volume hospital groups. CONCLUSION: An inverse correlation was noted
      between hospital volume and operative mortality in the present study, although
      wide variations in clinical outcome were noted among the very low-volume
      hospitals. Further analysis is warranted using risk-adjusted data.

PMID- 18066640
TI  - Early postoperative mobilization with walking at 4 hours after lobectomy in lung
      cancer patients.
AB  - OBJECTIVES: The aim of this study was to determine whether walking at 4 h after
      surgery as a more aggressive way to proceed with early mobilization could be a
      safe approach compared with the patients who walked the day after surgery.
      METHODS: We encouraged patients who had lobectomy for non-small-cell lung cancer
      at Kansai Medical University Hospital to walk at 4 h after surgery and start
      pulmonary rehabilitation between January 2003 and June 2005. A group of 36
      patients walked at 4 h after surgery. We retrospectively reviewed the
      postoperative courses of the patients and compared them with 50 patients who
      walked the next day during the same period. RESULTS: No patient had major trouble
      with chest drainage tube, and no patients fell when walking at 4 h. Amount of
      drainage, changing rates of the heart load during the walking, and pain scores
      after walking did not show significant differences in patients walking at 4 h and
      those walking the next day. Although four patients who walked the next day had an
      arterial oxygen partial pressure/inspired oxygen concentration ratio of <300 on
      day 3, none in the patients walking at 4 h had a ratio below this level. Among
      the patients walking at 4 h, 24 (67%) needed oxygenation for less than 2 days
      compared with 17 (34%) of the patients walking the next day. CONCLUSION: Walking
      at 4 h after lobectomy in patients with non-small-cell lung cancers is a safe
      approach to starting pulmonary rehabilitation after surgery.

PMID- 18066641
TI  - Repair of traumatic tricuspid regurgitation by bicuspidization.
AB  - Traumatic tricuspid regurgitation is a fairly rare complication following blunt
      chest trauma but not as uncommon as it was believed to be before the advent of
      transthoracic echocardiography. We report a case of severe tricuspid
      regurgitation with ruptured chordae tendineae 10 years after blunt chest trauma
      that was successfully repaired with a simple method. The operative technique
      consisted of plication of the anteroposterior commissure to create a bicuspid
      valve, along with ring annuloplasty.

PMID- 18066642
TI  - Successful repair of ascending aortic pseudoaneurysm using autograft patch from
      fascia lata and saphenous vein.
AB  - An 80-year-old man developed a pseudoaneurysm in the ascending aorta due to
      mediastinitis following cardiac surgery. We successfully repaired the
      pseudoaneurysm with an autograft patch harvested from fascia lata and the
      saphenous vein. The repair, which was carried out in two layers, can be expected
      to be durable.

PMID- 18066643
TI  - Edge-to-edge tricuspid valve repair in hypoplastic left heart syndrome.
AB  - Tricuspid regurgitation (TR) is known to be a risk factor for mortality in the
      surgical management of patients with hypoplastic left heart syndrome (HLHS).
      Concomitant repair for TR should be considered when the TR is moderate to severe
      to achieve successful Fontan completion. The present case was a 20-month-old girl
      who was diagnosed with HLHS (mitral atresia and aortic atresia). She underwent a
      Norwood procedure as the first palliation followed by a Glenn procedure. After
      that, she gradually developed TR, which progressed to a severe state at the time
      of the Fontan procedure. An edge-to-edge tricuspid valve repair, in which the
      anterior and septal leaflets were sutured together, was performed simultaneously
      with the extracardiac Fontan procedure. Discharge echocardiography revealed that
      the degree of TR was less than mild. The technique is simple, not time-consuming,
      and may be an effective adjunct for successful completion of the Fontan procedure
      in these patients.

PMID- 18066644
TI  - Simple surgical treatment for pleuroperitoneal communication without interruption
      of continuous ambulatory peritoneal dialysis.
AB  - Pleuroperitoneal communication is a complication of continuous ambulatory
      peritoneal dialysis (CAPD) that can necessitate cessation of CAPD. Hemodialysis
      was started on a 52-year-old woman and shifted to CAPD 1 month later. However, 18
      days after initiation of CAPD, her chest radiograph showed a right-side
      hydrothorax. Thoracentesis yielded a colorless pleural effusion with markedly
      higher glucose levels than in her serum, indicating the presence of
      pleuroperitoneal communication. Three days later, thoracoscopic surgery was
      performed. A colored dialysis solution preoperatively injected into the abdominal
      cavity identified intraoperatively leakage from the diaphragm. The leakage points
      were closed by a no-knife-type automatic stapler with absorbable polyglycolic
      acid felt and fibrin glue. CAPD was restarted on the operative day, and there was
      no recurrence of the right hydrothorax. We conclude that this simple method can
      be used effectively to treat pleuroperitoneal communication.

PMID- 18066645
TI  - Use of the pericardial cord as a substitute for an infected mitral prosthetic
      ring associated with aortic prosthetic valve endocarditis.
AB  - We report the case of a 61-year-old man with prosthetic valve endocarditis after
      both aortic valve replacement and mitral annuloplasty. Necrotic tissue and
      dehiscence of the suture line in the aortic annulus were found, and the infection
      extended to the anterior portion of the mitral prosthetic ring. The autologous
      pericardial cord was used as a substitute for the infected mitral prosthetic
      ring, and aortic root replacement was performed with a stentless bioprosthesis.
      The autologous pericardial cord was useful as a substitute for an infected mitral
      prosthetic ring.

PMID- 18066646
TI  - Thymoma with spontaneous regression and disappearance of pleural effusion.
AB  - A 31-year-old woman was admitted to our hospital with sudden onset of chest pain.
      Chest radiography and computed tomography (CT) on admission showed an anterior
      mediastinal tumor with left pleural effusion, which was diagnosed as an
      inoperable malignant mediastinal tumor. However, 3 weeks after admission CT
      showed that the tumor was diminishing and the pleural effusion had disappeared
      without any treatment. CT-guided needle biopsy was performed, but diagnosis was
      impossible because most of the specimen was necrotic. A biopsy during video
      assisted thoracic surgery was then performed. The intraoperative finding showed
      that the tumor was round, well mobilized, and did not invade adjacent structures.
      It was then assumed to be a benign teratoma that had been ruptured into the
      thoracic cavity. The operation was converted to a thoracotomy to resect it, but
      it could not be completely resected because of inflammatory adhesions to the
      mediastinum. Two months later, total thymectomy was performed through a median
      sternotomy because the tumor was pathologically diagnosed as a thymoma.

PMID- 18066647
TI  - New-model ultrasonically activated shears for hemostatic sectioning during video
      assisted thoracic surgery.
AB  - During video-assisted-thoracic surgery (VATS), bleeding limits the field of view
      and requires frequent exchange of surgical instruments through ports,
      complicating the surgical procedure. The poor video view also increases the risk
      of vessel injury. Attention must be paid to hemostasis to achieve safe, smooth
      VATS. The Harmonic Scalpel (HS) is able to grasp and divide tissues while sealing
      small vessels, which often cause bleeding during electrocautery, and lymphatic
      vessels. We obtained experience using a new model of HS, which appears effective
      for separating membranous or streak adhesions, cutting pulmonary parenchyma, and
      dividing lymphatic tissues. Compared to previous models, it allows superior
      handling during VATS. Tissue holding with this HS is greatly improved.

PMID- 18066648
TI  - Chemotherapy and the tumor microenvironment: the contribution of circulating
      endothelial cells.
AB  - Anti-angiogenic drugs, alone or in combination with chemotherapeutics, are
      increasingly used by medical oncologists. In many cases, however, their mechanism
      of action and the tailoring of optimal dosage/schedule are still elusive.
      Circulating endothelial cell (CEC) and progenitor (CEP) number and viability are
      modulated in a large series of diseases including cancer, and look promising as
      surrogate biomarkers for the definition of the optimal biological dose of anti
      angiogenic drugs and for patients' stratification. Along with CECs and CEPs,
      potential EC- and CEP-related surrogate molecular markers such as VE-Cadherin and
      CD133 are currently under preclinical and clinical investigation.

PMID- 18066649
TI  - A "class action" against the microenvironment: do cancer cells cooperate in
      metastasis?
AB  - The authors review how cancer cells may cooperate in metastasis by means of
      microenvironmental changes. The main mechanisms underlying this cooperation are
      clustered migration of cancer cells, extracellular matrix degradation, paracrine
      loops of released signaling factors and/or induction of adhesion molecules on
      stromal cells. Another critical factor could be temporal cooperation: successive
      waves of cancer cells may induce progressive conditioning of the
      microenvironment. The "class action" of cancer cells against the microenvironment
      involves successive steps of the metastatic process: invasion of the primary
      tumor microenvironment, collective migration through the extracellular matrix,
      blood vessel disruption, vascular or lymphatic tumor emboli, establishment of a
      premetastatic niche by secreted factors and endothelial precursor recruitment,
      induction of cell adhesion molecule expression in endothelial cells,
      extravasation, micrometastasis dormancy and establishment of a new growth in
      distant sites. As a result, after completion of the metastatic process, the
      series of microenvironmental changes from the primary tumor to the metastatic
      site may promote colonization of metastases by nonmetastatic cancer cells of the
      primary tumor.

PMID- 18066650
TI  - Immune cells as mediators of solid tumor metastasis.
AB  - Outgrowths of disseminated metastases remain the primary cause of mortality in
      cancer patients; however, molecular and cellular mechanisms regulating metastatic
      spread remain largely elusive. Recent insights into these mechanisms have refined
      the seed and soil hypothesis and it is now recognized that metastasis of solid
      tumors requires collaborative interactions between malignant cells and a diverse
      assortment of "activated" stromal cells at both primary and secondary tumor
      locations. Specifically, persistent pro-tumor immune responses (inflammation),
      now generally accepted as potentiating primary tumor development, are also being
      recognized as mediators of cancer metastasis. Thus, novel anti-cancer therapeutic
      strategies targeting molecular and/or cellular mechanisms regulating these
      collaborative interactions may provide efficacious relief for metastatic disease.
      This review focuses on recent literature revealing new mechanisms whereby immune
      cells regulate metastatic progression, with a primary focus on breast cancer.

PMID- 18066652
TI  - Risk, suffering and competing narratives in the psychiatric assessment of an
      Iraqi refugee.
AB  - This paper highlights the problem of "place" for an Iraqi refugee who, for years,
      had been tortured and imprisoned in his home country. Specifically, the paper
      presents a case study of a clinical encounter with this refugee, who had come to
      the attention of an Australian Crisis Assessment and Treatment Team. Drawing from
      narrative theory, the paper describes the chaotic nature of the encounter to show
      how the diverse motives, claims and actions of those present expose the struggle
      involved in the emplotment of an emerging narrative. The case study is
      constructed and analysed to illustrate the interpretive machinery of "clinical
      reasoning" and, in particular, the tension and play between "paradigmatic
      thinking" and "narrative thinking." More generally, this analysis follows the
      work of social scientists who seek to expand methodologies for writing about
      human suffering.

PMID- 18066651
TI  - Epicatechin gallate increases glutamate uptake and S100B secretion in C6 cell
      lineage.
AB  - There is a current interest in dietary compounds, such as green tea polyphenols,
      that can favor protection against a variety of brain disorders, including
      Alzheimer's disease, ischemia, and stroke. The objective of the present study was
      to investigate the effects of (-)-epicatechin-3-gallate (ECG), one of three three
      major green tea antioxidants, on C6 lineage cells. Here, we evaluated cell
      morphology and integrity and specific astrocyte activities; glutamate uptake and
      secretion of S100B in the presence of 0.1, 1 and 10 microM ECG. During 6 h of
      incubation, cell morphology was altered only at 10 microM ECG; however, after 24
      h of treatment, cells become stellate in the presence of all concentrations of
      ECG. Loss of cell integrity was observed after 24 h with 10 microM ECG and
      represented only 6% of cells, in contrast with 2% observed at basal conditions.
      ECG (1-10 microM) induced a decrease (about 36%) in glutamate uptake after 1 h of
      incubation. After 6 h, an opposite effect occurred and ECG induced a sustained
      increase in glutamate uptake of about 70% from 0.1 microM. In addition, a
      significant increase in S100B was observed at 1 microM ECG (36%) and 10 microM
      ECG (69%) after 1 h, in contrast to 6 h of treatment, where all doses of ECG
      induced a significant increase (about 60%) in S100B secretion. These data
      demonstrate that ECG induces a significant improvement in glutamate uptake and
      S100B secretion in C6 cells, indicating that ECG could contribute to the
      neuroprotective role of astroglial cells.

PMID- 18066653
TI  - Forced unfolding of apocytochrome b5 by steered molecular dynamics simulation.
AB  - Apocytochrome b5 (apocyt b5), a small b-type cytochrome with heme prosthetic
      group removal, has been subjected to steered molecular dynamics (SMD) simulations
      for investigating the consequences of mechanical force-induced unfolding. Both
      constant velocity (0.5 and 1.0 A/ps) and constant force (500, 750 and 1000 pN)
      stretching have been employed to model forced unfolding of apocyt b5. The results
      of SMD simulations elucidate that apocyt b5 is protected against external stress
      mainly through the interstrand hydrogen bonding between its beta1-beta2 and beta2
      beta3 strands, highlighting the importance of hydrophobic core 2 in stabilization
      of apocyt b5. The existence of intermediate states manifested by current
      simulations in the forced unfolding pathway of apocyt b5 is different from the
      observations in pervious thermal or chemical unfolding studies in the absence of
      force. The present study could thus provide insights into the relationship
      between the two cooperative functional modules of apocyt b5 and also guide the
      rational molecular design of heme proteins.

PMID- 18066654
TI  - Preparation and properties of recombinant rat and human procholecystokinin(57
      95).
AB  - Recombinant human progastrin(6-80) binds two ferric ions with an apparent
      dissociation constant of 2.2 +/- 0.1 microM [Baldwin (2004) Protein J 23:65-70].
      The aims of the present study were to express fragments of recombinant
      procholecystokinin and to determine whether or not they bound ferric ions.
      Recombinant rat and human procholecystokinin(57-95) were expressed as glutathione
      S-transferase fusion proteins in E. coli. The fusion proteins were bound to
      glutathione-agarose, cleaved with thrombin, and purified by reverse phase HPLC.
      Recombinant procholecystokinin(57-95) did not bind to either the CCK1 or CCK2
      receptor with high affinity. No change in absorption spectrum was observed on
      addition of ferric ions, and analysis of the quenching of tryptophan fluorescence
      observed in the presence of ferric ions indicated that binding to
      procholecystokinin(57-95) was at least 40-fold weaker than the binding of ferric
      ions to progastrin(6-80).

PMID- 18066655
TI  - Prediction of protein function improving sequence remote alignment search by a
      fuzzy logic algorithm.
AB  - The functional annotation of the new protein sequences represents a major
      drawback for genomic science. The best way to suggest the function of a protein
      from its sequence is by finding a related one for which biological information is
      available. Current alignment algorithms display a list of protein sequence
      stretches presenting significant similarity to different protein targets, ordered
      by their respective mathematical scores. However, statistical and biological
      significance do not always coincide, therefore, the rearrangement of the program
      output according to more biological characteristics than the mathematical scoring
      would help functional annotation. A new method that predicts the putative
      function for the protein integrating the results from the PSI-BLAST program and a
      fuzzy logic algorithm is described. Several protein sequence characteristics have
      been checked in their ability to rearrange a PSI-BLAST profile according more to
      their biological functions. Four of them: amino acid content, matched segment
      length and hydropathic and flexibility profiles positively contributed, upon
      being integrated by a fuzzy logic algorithm into a program, BYPASS, to the
      accurate prediction of the function of a protein from its sequence.

PMID- 18066656
TI  - The treatment with antibody of TNF-alpha reduces the inflammation, necrosis and
      fibrosis in the non-alcoholic steatohepatitis induced by methionine- and choline
      deficient diet.
AB  - To assess the effects of anti-TNF-alpha antibody (infliximab) in experimental
      steatohepatitis induced by methionine- and choline-deficient (MCD) diet. The
      study included thirty rats. One group received normal rat food, and two groups
      received MCD diet. The treatment group received a single dose intra-peritoneal
      infliximab (4 mg/kg), at week 8. MCD diet increased levels of AST, ALT, TNF
      alpha, TGF-beta(1), tissue and plasma MDA (p < 0.05 for each). Moreover, it led
      to steatosis, ballooning degeneration, inflammation, fibrosis and increased actin
      expression, histopathologically (p < 0.05 for each). In this experimental
      steatohepatitis anti-TNF-alpha antibody decreased the levels of AST, ALT, TGF
      beta(1) and plasma and tissue MDA (p < 0.05 for each). Moreover, inflammation,
      necrosis, actin expression and fibrosis decreased in anti-TNF-alpha group
      compared to placebo group (p < 0.05 for each). This study indicates that anti-TNF
      alpha antibody is effective on necrosis, inflammation and fibrosis in the
      experimental model of non-alcoholic steatohepatitis, induced by MCD diet.

PMID- 18066657
TI  - Spontaneous coordinated activity in cultured networks: analysis of multiple
      ignition sites, primary circuits, and burst phase delay distributions.
AB  - All higher order central nervous systems exhibit spontaneous neural activity,
      though the purpose and mechanistic origin of such activity remains poorly
      understood. We quantitatively analyzed the ignition and spread of collective
      spontaneous electrophysiological activity in networks of cultured cortical
      neurons growing on microelectrode arrays. Leader neurons, which form a mono
      synaptically connected primary circuit, and initiate a majority of network bursts
      were found to be a small subset of recorded neurons. Leader/follower firing delay
      times formed temporally stable positively skewed distributions. Blocking
      inhibitory synapses usually resulted in shorter delay times with reduced
      variance. These distributions are characterizations of general aspects of
      internal network dynamics and provide estimates of pair-wise synaptic distances.
      The resulting analysis produced specific quantitative constraints and insights
      into the activation patterns of collective neuronal activity in self-organized
      cortical networks, which may prove useful for models emulating spontaneously
      active systems.

PMID- 18066658
TI  - Evaluation of the serotonergic genes htr1A, htr1B, htr2A, and slc6A4 in
      aggressive behavior of golden retriever dogs.
AB  - Aggressive behavior displays a high heritability in our study group of Golden
      Retriever dogs. Alterations in brain serotonin metabolism have been described in
      aggressive dogs before. Here, we evaluate whether four genes of the canine
      serotonergic system, coding for the serotonin receptors 1A, 1B, and 2A, and the
      serotonin transporter, could play a major role in aggression in Golden
      Retrievers. We performed mutation screens, linkage analysis, an association
      study, and a quantitative genetic analysis. There was no systematic difference
      between the coding DNA sequence of the candidate genes in aggressive and non
      aggressive Golden Retrievers. An affecteds-only parametric linkage analysis
      revealed no strong major locus effect on human-directed aggression related to the
      candidate genes. An analysis of 41 single nucleotide polymorphisms (SNPs) in the
      1 Mb regions flanking the genes in 49 unrelated human-directed aggressive and 49
      unrelated non-aggressive dogs did not show association of SNP alleles, genotypes,
      or haplotypes with aggression at the candidate loci. We completed our analyses
      with a study of the effect of variation in the candidate genes on a collection of
      aggression-related phenotypic measures. The effects of the candidate gene
      haplotypes were estimated using the Restricted Maximum Likelihood method, with
      the haplotypes included as fixed effects in a linear animal model. We observed no
      effect of the candidate gene haplotypes on a range of aggression-related
      phenotypes, thus extending our conclusions to several types of aggressive
      behavior. We conclude that it is unlikely that these genes play a major role in
      the variation in aggression in the Golden Retrievers that we studied. Smaller
      phenotypic effects of these loci could not be ruled out with our sample size.

PMID- 18066659
TI  - A test of motivational plus nicotine replacement interventions for HIV positive
      smokers.
AB  - The purpose of this study was to test two combination motivational plus
      pharmacological interventions for smoking cessation among HIV positive smokers.
      Participants were 40 adults receiving HIV care who smoked daily reporting
      interest in smoking reduction. Measures were administered at baseline, 1-month,
      and 3-month follow-ups. Participants were randomly assigned to self-guided
      reading plus nicotine patch (n = 18) or motivational interviewing plus nicotine
      patch (n = 22). Groups did not differ at 3 months on biochemically-verified
      abstinence. The sample reduced cigarettes per day by half a pack and the percent
      of smoking days by 41%, and 22% were abstinent at 3-month follow-up. Compliance
      with the nicotine patch was poor and declined over time, but patch use was
      unrelated to carbon monoxide level at 3-month follow-up. Smoking cessation
      interventions for people with HIV can be helpful and should include components
      that encourage some smoke-free days, increase self-efficacy, and attend to
      adherence to nicotine replacement treatment.

PMID- 18066660
TI  - The development of delinquency and perceived friendship quality in adolescent
      best friendship dyads.
AB  - The present study examines both the unique and the combined role of best friends'
      delinquency and perceived friendship quality in the development of adolescent
      delinquency. Questionnaire data were gathered from 435 Dutch adolescent best
      friends (mean age at first wave = 12.97) over a period of 5 years with annual
      assessments. Results showed that mean levels of delinquency and perceived
      friendship quality increased over time. Adolescent best friends were highly
      similar in both mean levels and changes in delinquency over time. For boys,
      similarity in mean level delinquency between best friends was higher than for
      girls. In addition, only for boys, friends' delinquency is associated with
      increases in adolescent delinquency over time, and adolescents' delinquency is
      associated with increases in friends' delinquency over time. No bidirectional
      longitudinal associations were found between perceived friendship quality and
      adolescent delinquency. No interaction effects between friendship quality and
      friends' delinquency on adolescent delinquency were found. Thus, findings were
      more in support of the differential association theory than of the social control
      theory.

PMID- 18066662
TI  - Elastic fibers enhance the mechanical integrity of the human lumbar anulus
      fibrosus in the radial direction.
AB  - The anulus fibrosus of the human lumbar intervertebral disc has a complex,
      hierarchical structure comprised of collagens, proteoglycans, and elastic fibers.
      Recent histological studies have suggested that the elastic fiber network may
      play an important functional role. In this study, it was hypothesized that
      elastic fibers enhance the mechanical integrity of the extracellular matrix in
      the radial orientation, perpendicular to the plane containing the collagen
      fibers. Using a combination of biochemically verified enzymatic treatments and
      biomechanical tests, it was demonstrated that degradation of elastic fibers
      resulted in a significant reduction in both the initial modulus and the ultimate
      modulus, and a significant increase in the extensibility, of radially oriented
      anulus fibrosus specimens. Separate treatments and mechanical tests were used to
      account for any changes attributable to non-specific degradation of
      glycosaminoglycans. Additionally, histological assessments provided a unique
      perspective on structural changes in the elastic fiber network in radially
      oriented specimens subjected to tensile deformations. The results of this study
      demonstrate that elastic fibers play an important and unique role in the
      mechanical properties of the anulus fibrosus, and provide the basis for the
      development of improved material models to describe intervertebral disc
      mechanical behavior.

PMID- 18066661
TI  - Sero-epidemiology of hepatitis B among new refugees to Minnesota.
AB  - Hepatitis B virus (HBV) infection is endemic in many parts of the world, and
      prevailing conditions in refugee situations result in greater risk of infection.
      The objectives of this study were to determine the period prevalence of HBV
      infection among primary refugees in Minnesota during 1998-2001; describe trends
      in prevalence over time and identify patterns of infection and immunity in
      various refugee populations. A retrospective analysis of health examination data
      from the Minnesota Department of Health was conducted to examine serologic
      markers for hepatitis B: HBcAb, HbsAg, and HBsAb among 12,505 refugees who
      participated in the voluntary domestic health examination from 1998 to 2001. One
      hundred and eleven refugees had at least one immunization before arrival and were
      excluded. There was documented HBV test results in 8,754 (70.6%) of refugees;
      period prevalence of hepatitis B infection was 7.1%. Africans were three times
      more likely and Asians 2.4 times more likely to be infected than Europeans (P <
      0.001). Older African refugees and African males were more likely to be infected
      than younger African refugees and women African refugees (P < 0.001). Younger
      persons below 30 years of age accounted for over 70% of all infected refugees in
      this study. Reducing the burden of infection among refugees requires enhanced
      provider awareness as well as intensified efforts aimed at identifying new at
      risk populations, modifying risk factors, and implementing preventive and
      treatment strategies at various levels in the refugee resettlement process.

PMID- 18066663
TI  - Morphology and morphometry of human chronic spinal cord injury using diffusion
      tensor imaging and fuzzy logic.
AB  - Diffusion tensor imaging (DTI) was performed on regions rostral to the injury
      site in four human subjects with chronic spinal cord injury (SCI) and equivalent
      regions in four neurologically intact subjects. Apparent diffusion coefficients
      were measured and compared between subjects. A fuzzy logic tissue classification
      algorithm was used to segment gray and white matter regions for morphometric
      analysis, including comparisons of cross-sectional areas of gray and white matter
      along with frontal and sagittal diameters. Results indicated a general decrease
      in both longitudinal and transverse diffusivity in the upper cervical segments of
      subjects with chronic SCI. Further, a decrease in the cross-sectional area of the
      entire spinal cord was observed in subjects with SCI, consistent with severe
      atrophy of the spinal cord. These observations have implications in tracking the
      progression of SCI from the acute to the chronic stages. We conclude that DTI
      with fuzzy logic tissue classification has potential for monitoring morphological
      changes in the spinal cord in people with SCI.

PMID- 18066664
TI  - Accommodation and size-constancy of virtual objects.
AB  - Accommodation has been suspected as a contributor to size illusions in virtual
      environments (VE) due to the lack of appropriate accommodative stimuli in a VE
      for the objects displayed. Previous experiments examining size-constancy in VE
      have shown that monocular cues to depth that accompany the object are a major
      contributor to correct size perception. When these accompanying cues are removed
      perceived size varied with the object's distance from the subject, i.e., visual
      angle. If accommodation were the dominant mechanism contributing to a visual
      angle response [due to its action to keep physical objects clear] in this
      condition, an open-loop accommodation viewing condition might restore size
      constancy to this condition. Pinhole apertures were used to open-loop
      accommodation and examine if size-constancy might be restored when few
      accompanying monocular cues to depth were present. Visual angle performance when
      viewing a low cue environment was found with and without the use of the pinhole
      apertures. Thus, these results signify that accommodation does not play a
      dominate role in the loss of size-constancy in sparse visual environments often
      used in VE. These results suggest that size-constancy is driven by the inclusion
      of the remaining monocular cues to depth in VE as it is in the physical world.

PMID- 18066666
TI  - Multivariate system identification for cerebral autoregulation.
AB  - The effect of spontaneous beat-to-beat mean arterial blood pressure (ABP)
      fluctuations and breath-to-breath end-tidal carbon dioxide (PETCO2) and end-tidal
      oxygen (PETO2) fluctuations on beat-to-beat cerebral bloodflow velocity (CBFV)
      variations is studied using a multiple coherence function. Multiple coherence is
      a measure of the extent to which the output, CBFV, can be represented as a linear
      time invariant system of multiple input signals. Analysis of experimental
      measurements from 13 different healthy subjects reveal that, with additional
      inputs, PETCO2 and PETO2, the multiple coherence for frequencies <0.05 Hz is
      significantly higher than the corresponding values obtained for univariate
      coherence with a single input of ABP. The result illustrates that the low value
      of univariate coherence at small frequencies may be due to the effects of PETCO2
      and PETO2 fluctuations on CBFV variability. Moreover, it is also found that the
      transfer function between ABP and CBFVtime series identified from previous
      univariate techniques at low frequencies can be modified by CO2 and O2 reactivity
      and no longer represents pressure autoregulation only. Multivariate system
      identification provides a technique of incorporating additional variability and
      recovering from this artifact. Finally, a physiologically based model and its
      linear transfer function are used as a simulation tool to investigate possible
      causes of low univariate coherence.

PMID- 18066665
TI  - Effect of strain magnitude on the tissue properties of engineered cardiovascular
      constructs.
AB  - Mechanical loading is a powerful regulator of tissue properties in engineered
      cardiovascular tissues. To ultimately regulate the biochemical processes, it is
      essential to quantify the effect of mechanical loading on the properties of
      engineered cardiovascular constructs. In this study the Flexercell FX-4000T
      (Flexcell Int. Corp., USA) straining system was modified to simultaneously apply
      various strain magnitudes to individual samples during one experiment. In
      addition, porous polyglycolic acid (PGA) scaffolds, coated with poly-4
      hydroxybutyrate (P4HB), were partially embedded in a silicone layer to allow long
      term uniaxial cyclic mechanical straining of cardiovascular engineered
      constructs. The constructs were subjected to two different strain magnitudes and
      showed differences in biochemical properties, mechanical properties and
      organization of the microstructure compared to the unstrained constructs. The
      results suggest that when the tissues are exposed to prolonged mechanical
      stimulation, the production of collagen with a higher fraction of crosslinks is
      induced. However, straining with a large strain magnitude resulted in a negative
      effect on the mechanical properties of the tissue. In addition, dynamic straining
      induced a different alignment of cells and collagen in the superficial layers
      compared to the deeper layers of the construct. The presented model system can be
      used to systematically optimize culture protocols for engineered cardiovascular
      tissues.

PMID- 18066667
TI  - An introductory course to biomedical microsystems for undergraduates.
AB  - At the University of Cincinnati the state-of-the-art BioMEMS and Biomedical
      Microsystems research was successfully integrated within the undergraduate
      electrical engineering curricula through the development of a course Introduction
      to Biomedical Microsystems. In the first three course offerings, enrollment has
      spread beyond the initial target audience of the Department of Electrical and
      Computer Engineering, and now includes students from mechanical engineering,
      environmental engineering, computer engineering, and biomedical engineering. The
      use of research articles to supplement lecture materials worked effectively,
      providing undergraduate students with a real world perspective. Reading
      assignments, discussions of research papers, and short quizzes at the beginning
      of lectures were used to test understanding of concepts. This was also done to
      ensure that students were not overwhelmed by the multidisciplinary material or
      the pace of the course. This paper provides an overview of the course, summarizes
      results of student assessment, and discusses future improvements.

PMID- 18066668
TI  - Inhibition of toll-like receptor signaling in primary murine microglia.
AB  - Microglial cells respond to the herpes simplex virus (HSV)-1 by producing
      proinflammatory cytokines and chemokines. After this inflammatory burst, these
      cells undergo apoptotic cell death. We have recently demonstrated that both virus
      induced immune mediator production and apoptosis were induced through Toll-like
      receptor 2 (TLR2) signaling. Based upon these findings, we hypothesized that the
      inhibition of TLR2 signaling may serve as a means to alleviate excessive
      neuroinflammation. In the present study, we cloned four vaccinia virus (VV)
      proteins, which have been reported to disrupt either TLR signaling or NF-kappaB
      activation, and overexpressed them in HEK293T cells stably expressing murine TLR2
      and in primary murine microglia. Using an NF-kappaB-driven luciferase reporter
      gene assay, we show that upon stimulation with HSV and Listeria monocytogenes,
      all four vaccinia proteins inhibited TLR2 signaling with different levels of
      inhibition in the TLR2-expressing cell line and primary microglia. We found
      similar results when microglial cells were stimulated with the TLR4 ligand LPS
      and the TLR9 ligand CpG ODN. Taken together, these data provide evidence that
      these VV proteins can function as inhibitors of TLR signaling in primary
      microglial cells.

PMID- 18066669
TI  - Guest editorial for special issue on "ADME and Physical Properties".

PMID- 18066671
TI  - Exposure to traffic emissions throughout life and risk of breast cancer.

PMID- 18066670
TI  - The karyotype and 5S rRNA genes from Spanish individuals of the bat species
      Rhinolophus hipposideros (Rhinolophidae; Chiroptera).
AB  - The karyotype of individuals of the species Rhinolophus hipposideros from Spain
      present a chromosome number of 2n = 54 (NFa = 62). The described karyotype for
      these specimens is very similar to another previously described in individual
      from Bulgaria. However, the presence of one additional pair of autosomal
      acrocentric chromosomes in the Bulgarian karyotype and the differences in X
      chromosome morphology indicated that we have described a new karyotype variant in
      this species. In addition, we have analyzed several clones of 1.4 and 1 kb of a
      PstI repeated DNA sequence from the genome of R. hipposideros. The repeated
      sequence included a region with high identity with the 5S rDNA genes and flanking
      regions, with no homology with GenBank sequences. Search for polymerase III
      regulatory elements demonstrated the presence of type I promoter elements (A-box,
      Intermediate Element and C-box) in the 5S rDNA region. In addition, upstream
      regulatory elements, as a D-box and Sp1 binding sequences, were present in
      flanking regions. All data indicated that the cloned repeated sequences are the
      functional rDNA genes from this species. Finally, FISH demonstrated the presence
      of rDNA in nine chromosome pairs, which is surprising as most mammals have only
      one carrier chromosome pair.

PMID- 18066672
TI  - Prognostic factors in women with breast cancer: inequalities by ethnicity and
      socioeconomic position in New Zealand.
AB  - OBJECTIVE: To investigate differences in breast cancer prognostic factors between
      ethnic and socioeconomic groups in New Zealand. METHODS: We analyzed all 21,586
      breast cancer cases on the New Zealand Cancer Registry (July 1994-June 2004).
      Maori, Pacific, and non-Maori/non-Pacific women were categorized according to
      ethnicity on the Registry. Deprivation was analyzed as quintiles of the New
      Zealand Deprivation Index 2001, an area-based measure of socioeconomic position.
      Logistic regression was used to estimate age-adjusted odds ratios (OR) (95%
      confidence intervals (CI)). RESULTS: Maori and Pacific women were more likely to
      have non-local stage, less well differentiated cancer, larger tumors and positive
      human epidermal growth factor receptor-type 2 (HER-2) status than non-Maori/non
      Pacific women. Maori were less likely and Pacific women more likely than non
      Maori/non-Pacific women to have negative oestrogen (ER) and progesterone receptor
      (PR) status. Adjusting for deprivation did not materially alter the results.
      Women living in more deprived areas had a higher risk of non-local stage and
      larger tumors. These associations were only partially explained by ethnicity.
      There was no relationship between tumor grade, ER, PR or HER-2 status and
      deprivation. CONCLUSIONS: Our results confirm that Maori, Pacific and low
      socioeconomic women present with poor prognosis breast tumors.

PMID- 18066673
TI  - Cancer incidence and mortality patterns among specific Asian and Pacific Islander
      populations in the U.S.
AB  - OBJECTIVES: We report cancer incidence, mortality, and stage distributions among
      Asians and Pacific Islanders (API) residing in the U.S. and note health
      disparities, using the cancer experience of the non-Hispanic white population as
      the referent group. New databases added to publicly available SEER*Stat software
      will enable public health researchers to further investigate cancer patterns
      among API groups. METHODS: Cancer diagnoses among API groups occurring from 1
      January 1998 to 31 December 2002 were included from 14 Surveillance,
      Epidemiology, and End Results (SEER) Program state and regional population-based
      cancer registries covering 54% of the U.S. API population. Cancer deaths were
      included from the seven states that report death information for detailed API
      groups and which cover over 68% of the total U.S. API population. Using detailed
      racial/ethnic population data from the 2000 decennial census, we produced
      incidence rates centered on the census year for Asian Indians/Pakistanis,
      Chinese, Filipinos, Guamanians, Native Hawaiians, Japanese, Kampucheans, Koreans,
      Laotians, Samoans, Tongans, and Vietnamese. State vital records offices do not
      report API deaths separately for Kampucheans, Laotians, Pakistanis, and Tongans,
      so mortality rates were analyzed only for the remaining API groups. RESULTS:
      Overall cancer incidence rates for the API groups tended be lower than overall
      rates for non-Hispanic whites, with the exception of Native Hawaiian women (All
      cancers rate = 488.5 per 100,000 vs. 448.5 for non-Hispanic white women). Among
      the API groups, overall cancer incidence and death rates were highest for Native
      Hawaiian and Samoan men and women due to high rates for cancers of the prostate,
      lung, and colorectum among Native Hawaiian men; cancers of the prostate, lung,
      liver, and stomach among Samoan men; and cancers of the breast and lung among
      Native Hawaiian and Samoan women. Incidence and death rates for cancers of the
      liver, stomach, and nasopharynx were notably high in several of the API groups
      and exceeded rates generally seen for non-Hispanic white men and women. Incidence
      rates were lowest among Asian Indian/Pakistani and Guamanian men and women and
      Kampuchean women. Asian Indian and Guamanian men and women also had the lowest
      cancer death rates. Selected API groups had less favorable distributions of stage
      at diagnosis for certain cancers than non-Hispanic whites. CONCLUSIONS: Possible
      disparities in cancer incidence or mortality between specific API groups in our
      study and non-Hispanic whites (referent group) were identified for several
      cancers. Unfavorable patterns of stage at diagnosis for cancers of the colon and
      rectum, breast, cervix uteri, and prostate suggest a need for cancer control
      interventions in selected groups. The observed variation in cancer patterns among
      API groups indicates the importance of monitoring these groups separately, as
      these patterns may provide etiologic clues that could be investigated by analytic
      epidemiological studies.

PMID- 18066674
TI  - Interseasonal distribution and partitioning of heavy metals in subtidal sediment
      of Qua Iboe Estuary and associated Creeks, Niger Delta (Nigeria).
AB  - An analysis of the distribution and chemical forms of selected metals: cadmium
      (Cd), chromium (Cr), copper (Cu), nickel (Ni) and lead (Pb) in subtidal sediments
      of Qua Iboe Estuary and adjourning creeks, collected between June 2000 and
      January 2001, were studied using a sequential chemical extraction method. The
      concentration of metals in each extracted fraction was determined using
      inductively coupled plasma spectrometer (ICP-AES). Pb, Cd and Cu appear to be the
      most abundant metal in the sediments of the systems, and are predominantly
      associated with the residual, organic and oxidisable phases. Results indicate
      that there are also insignificant components that are bound to both the
      exchangeable and carbonates fractions. Ni is largely associated with bioavailable
      phases with insignificant bound to organic matter and residual fractions. In
      general, an insignificant component of Cd and Pb are bound to organic matter
      phase. Moreover, speciation results indicate that metal contamination in the
      ecosystems investigated primarily comes from human-mediated sources. Thus, based
      on index of geoaccumulation calculated, sediments of these ecosystems have been
      classified as uncontaminated by Cr, Cu and Ni, strongly contaminated by Pb and
      extremely contaminated by Cd.

PMID- 18066675
TI  - A bio-optical model based method of estimating total suspended matter of Lake
      Taihu from near-infrared remote sensing reflectance.
AB  - Total suspended matter is an important water quality parameter, and plays a key
      role in water quality evaluation, especially of inland waters. Many different
      methods have been developed to estimate TSM from remote sensing data, in which
      empirical methods and model-based methods are two types of commonly used methods.
      Compared with empirical methods, model-based methods have the advantages of
      definite physical meanings, high robustness and retrieval accuracy. In model
      based methods, matrix inversion method is commonly used in monitoring water
      qualities of inland waters. However, matrix inversion method has to predetermine
      some optical parameters by empirical values or simplified optical model, which
      may introduce some errors in retrieved water quality parameters. In order to
      overcome the shortcomings of matrix inversion method and increase the estimating
      accuracy of total suspended mater, in this paper, a bio-optical model based
      method is developed, which estimates total suspended mater by using remote
      sensing reflectance of two near-infrared bands. This method is validated by in
      situ experiment data measured in Lake Taihu, a big turbid lake in eastern China.
      The results show that this method has better performance than matrix inversion
      method. The average relative error of the estimated total suspended matter by
      this method is only 13.0%, which is much smaller than the errors by matrix
      inversion method (32.7%). This method has the advantages of definite physical
      meaning, easiness to carry out, and high estimating accuracy. However, the
      applicable scope of this method has limitations: it can only be applied to
      optically deep waters with high concentrations of total suspended matter.

PMID- 18066676
TI  - Potential for reducing air pollution from oil refineries.
AB  - Islamic Republic of Iran has to invest 95 billion US$ for her new oil refineries
      to the year 2045. At present, the emission factors for CO(2), NO( x ) and SO(2)
      are 3.5, 4.2 and 119 times higher than British refineries, respectively. In order
      to have a sustainable development in Iranian oil refineries, the government has
      to set emission factors of European Community as her goal. At present CO(2) per
      Gross Domestic Production (GDP) in the country is about 2.7 kg CO(2) as 1995's
      USD value that should be reduced to 1.25 kg CO(2)/GDP in the year 2015. Total
      capital investment for such reduction is estimated at 346 million USD which is
      equal to 23 USD/ton of CO(2). It is evident that mitigation of funds set by Clean
      Development Mechanism (3 to 7 USD/tons of CO(2)) is well below the actual capital
      investment needs. Present survey shows that energy efficiency promotion potential
      in all nine Iranian oil refineries is about 165,677 MWh/year through utilization
      of more efficient pumps and compressors. Better management of boilers in all nine
      refineries will lead to a saving of 273 million m(3) of natural gas per year.

PMID- 18066678
TI  - Diversity of basidiomycetous phylloplane yeasts belonging to the genus Dioszegia
      (Tremellales) and description of Dioszegia athyri sp. nov., Dioszegia butyracea
      sp. nov. and Dioszegia xingshanensis sp. nov.
AB  - From approximately 200 basidiomycetous yeast isolates forming orange or orange
      red colonies isolated from senescent leaves collected in different regions of
      China, 29 representative strains varying in their geographic distribution and
      ballistoconidium forming ability were selected for further phenotypic and
      molecular taxonomic studies. Sequence analysis of the large subunit (26S) rDNA
      D1/D2 domain and the internal transcribed spacer (ITS) region including 5.8S rRNA
      from the strains resulted in the recognition of seven Dioszegia species,
      including four described species, namely D. aurantiaca, D. fristingensis, D.
      hungarica and D. zsoltii var. zsoltii and D. zsoltii var. yunnanensis, and three
      undescribed species. The three new species are described as Dioszegia athyri sp.
      nov. (type strain: CB 159(T) = AS 2.2559(T) = CBS 10119(T)), Dioszegia butyracea
      sp. nov. (type strain: CB 261(T) = AS 2.2600(T) = CBS 10122(T)) and Dioszegia
      xingshanensis sp. nov. (type strain: HB 1.4(T) = AS 2.2481(T) = CBS 10120(T)) in
      the present study.

PMID- 18066677
TI  - Statin therapy in peritoneal dialysis patients: effects beyond lipid lowering.
AB  - Lipid abnormalities, and especially hypertriglyceridaemia, are a prominent
      feature of peritoneal dialysis (PD) patients. The results from several studies
      have shown that statins are effective and safe lipid-lowering agents in these
      individuals. Besides lipid lowering, current evidence suggests that these agents
      exert multiple beneficial effects on PD patients. Statins may maintain residual
      kidney function by altering the response of the kidneys to dyslipidaemia and,
      thus, slow the progression of renal failure in PD patients. Also, statins may
      reduce the incidence of cardiovascular events, as well as morbidity and mortality
      rates in this high-risk group. However, despite the multiple beneficial effects,
      PD patients receive suboptimal statin treatment. Apart from the German Dialysis
      and Diabetes (4D) study, no other prospective, randomised controlled trial has
      investigated the effects of statin treatment on dialysis patients. The results of
      large-scale, multi-centre randomised controlled studies (such as AURORA and
      SHARP) are expected to define the role of statin therapy in this high-risk
      population.

PMID- 18066679
TI  - Prevalence of the prothrombin G20210A polymorphism in the Lebanese population:
      use of a reverse hybridization strip assay approach.
AB  - The factor II (prothrombin) G20210A gene polymorphism is the second most common
      SNP reported in VTE where it is associated with elevated plasma prothrombin
      levels and with a 3-fold increased risk. We studied the distribution of the G/G,
      G/A, and A/A genotypes of the Prothrombin G20210A gene mutation in the general
      Lebanese population using a novel technique in order to assess their prevalence,
      compare the results to previously reported data and to describe an available
      method that will permit easy and fast identification of the mutation. Prothrombin
      different genotypes were determined using the Cardiovascular Disease (CVD)
      StripAssay which is based on a Polymerase Chain Reaction-Reverse hybridization
      technique and DNA from 205 unrelated healthy donors from our HLA-bank was used.
      The prevalence of G/G, G/A, and A/A genotypes was found to be 98.54, 1.46, and
      0%, respectively, with G and A allelic frequency of 99 and 1%, respectively. The
      sampled Lebanese population showed prothrombin genotypes distribution similar to
      Caucasians, and our results are comparable to other reports on the Lebanese
      healthy individuals. However, this is the first report on the prevalence of
      prothrombin G20210A mutation using this technique. Our results suggest that this
      approach is reliable and can be used as an assessment for thrombophilia profile.
      In addition, future investigations should be conducted to assess the contribution
      of the prothrombin G20210A mutation, on its own and in collaboration with other
      factors, in various clinical entities notably VTE.

PMID- 18066680
TI  - Determining public policy and resource allocation priorities for mitigating
      natural hazards: a capabilities-based approach.
AB  - This paper proposes a Capabilities-based Approach to guide hazard mitigation
      efforts. First, a discussion is provided of the criteria that should be met by an
      adequate framework for formulating public policy and allocating resources. This
      paper shows why a common decision-aiding tool, Cost-benefit Analysis, fails to
      fulfill such criteria. A Capabilities-based Approach to hazard mitigation is then
      presented, drawing on the framework originally developed in the context of
      development economics and policy. The focus of a Capabilities-based Approach is
      protecting and promoting the well-being of individuals. Capabilities are
      dimensions of well-being and specified in terms of functionings. Functionings
      capture the various things of value an individual does or becomes in his or her
      life, including being alive, being healthy, and being sheltered. Capabilities
      refer to the real achievability of specific functionings. In the context of
      hazard mitigation, from a Capabilities-based Approach, decision- and policy
      makers should consider the acceptability and tolerability of risks along with the
      affectability of hazards when determining policy formulation and resource
      allocation. Finally, the paper shows how the proposed approach satisfies the
      required criteria, and overcomes the limitations of Cost-benefit Analysis, while
      maintaining its strengths.

PMID- 18066681
TI  - Ethical education in software engineering: responsibility in the production of
      complex systems.
AB  - Among the various contemporary schools of moral thinking, consequence-based
      ethics, as opposed to rule-based, seems to have a good acceptance among
      professionals such as software engineers. But naive consequentialism is
      intellectually too weak to serve as a practical guide in the profession. Besides,
      the complexity of software systems makes it very hard to know in advance the
      consequences that will derive from professional activities in the production of
      software. Therefore, following the spirit of well-known codes of ethics such as
      the ACM/IEEE's, we advocate for a more solid position in the ethical education of
      software engineers, which we call 'moderate deontologism', that takes into
      account both rules and consequences to assess the goodness of actions, and at the
      same time pays an adequate consideration to the absolute values of human dignity.
      In order to educate responsible professionals, however, this position should be
      complemented with a pedagogical approach to virtue ethics.

PMID- 18066682
TI  - Primary mediastinal large B-cell lymphoma mimicking liposarcoma.
AB  - A 78-year-old man consulted for acute exacerbation of chronic obstructive
      pulmonary disease (COPD) and an incidental finding of an anterior mediastinal
      tumor on chest radiograph was noted on admission. Chest computed tomography (CT)
      revealed a fat-containing mediastinal mass with solid component. Mediastinal
      liposarcoma was the initial diagnosis based on image characteristics but
      histopathologic examination of the excised tumor revealed lymphoma infiltration
      of the mediastinal adipose tissue. To our knowledge, this is the first case
      report of lymphomatous growth in mediastinal lipomatosis.

PMID- 18066683
TI  - Monolithic macroporous albumin/chitosan cryogel structure: a new matrix for
      enzyme immobilization.
AB  - A novel monolithic macroporous material was developed by cross-linking hen egg
      albumin (HEA) and chitosan with glutaraldehyde at subzero temperatures. A
      macroporous cryogel structure allowed efficient mass transport of solutes within
      the material. In one application, albumin was partially replaced with active
      enzymes (glucose oxidase and horseradish peroxidase) resulting in the production
      of macroporous biocatalyst preparations suitable for flow-injection analysis of
      glucose in the low millimolar range. In another application, the proteolytic
      enzymes savinase and esperase were coupled to the macroporous structure via free
      amino groups on the pore walls using glutaraldehyde as cross-linker/spacer agent.
      The low hydraulic resistance of the matrix allowed for the development of a
      generic, high-performance online protein digestion system utilizing the wall
      bound proteases.

PMID- 18066684
TI  - High-frequency priming stimulation does not enhance the effect of low-frequency
      rTMS in the treatment of tinnitus.
AB  - Based on its ability to reduce the excitability of the cortex locally, low
      frequency repetitive transcranial magnetic stimulation (rTMS) has been
      investigated for the treatment of hyperexcitability disorders such as auditory
      hallucinations and tinnitus. Results are promising, but characterized by only
      moderate improvement and a high inter-individual variability. Experimental data
      from motor cortex stimulation in healthy subjects indicates that the depressant
      effect of low-frequency rTMS can be enhanced by high-frequency priming
      stimulation. Here we will investigate whether high-frequency priming also
      improves the therapeutic efficacy of low-frequency rTMS in a clinical
      application. 32 patients with chronic tinnitus were randomly assigned to either a
      standard protocol of low-frequency rTMS (110% motor threshold, 1 Hz, 2000
      stimuli/day) or a stimulation protocol in which priming stimulation with 6 Hz
      (90% motor threshold, 960 stimuli) preceded low-frequency rTMS (110% motor
      threshold, 1 Hz, 1040 stimuli/day). Stimulation was applied over the left
      auditory cortex by using MRI-guided coil positioning. The treatment outcome was
      assessed with a standardized tinnitus questionnaire. There was no significant
      difference between the standard protocol and the protocol involving priming
      stimulation. Both stimulation protocols resulted in significant clinical
      improvement after 10 days of stimulation, as compared to baseline. Our data does
      not support an enhancing effect of higher frequency priming on low-frequency rTMS
      in the treatment of tinnitus.

PMID- 18066686
TI  - Mammalian aldehyde oxidases: genetics, evolution and biochemistry.
AB  - Mammalian aldehyde oxidases are a small group of proteins belonging to the larger
      family of molybdo-flavoenzymes along with xanthine oxidoreductase and other
      bacterial enzymes. The two general types of reactions catalyzed by aldehyde
      oxidases are the hydroxylation of heterocycles and the oxidation of aldehydes
      into the corresponding carboxylic acids. Different animal species are
      characterized by a different complement of aldehyde oxidase genes. Humans contain
      a single active gene, while marsupials and rodents are characterized by four such
      genes clustering at a short distance on the same chromosome. At present, little
      is known about the physiological relevance of aldehyde oxidases in humans and
      other mammals, although these enzymes are known to play a role in the metabolism
      of drugs and compounds of toxicological importance in the liver. The present
      article provides an overview of the current knowledge of genetics, evolution,
      structure, enzymology, tissue distribution and regulation of mammalian aldehyde
      oxidases.

PMID- 18066685
TI  - Design and development of a surgical skills simulation curriculum.
AB  - BACKGROUND: A number of significant changes have forced surgical educators to re
      evaluate the adequacy of traditional forms of surgical skills training.
      MATERIALS: A review of the literature reveals that surgical simulation has
      emerged as a useful adjunct to help educators adjust to the demands of an ever
      changing surgical practice environment. As such, integration of simulation
      technology into a busy surgical training program has now become a priority for
      training programs worldwide. RESULTS: Successful integration requires a
      disciplined and dedicated approach to the appropriate use of all forms of
      available simulation in a well-designed curriculum. CONCLUSION: This manuscript
      provides a discussion of how this can be achieved using a sequential, modular,
      criterion-based framework, providing details of the rationale behind such an
      approach and current examples of how it can be integrated.

PMID- 18066687
TI  - siRNA as a molecular tool for use in Aspergillus niger.
AB  - Gene silencing using siRNA has been examined in the industrially-important
      fungus, Aspergillus niger. Protoplasts of an A. niger strain containing a single
      genomic copy of the Escherichia coli uidA gene, encoding beta-glucuronidase
      (GUS), under control of the A. niger glaA promoter at the same genomic locus,
      were exposed to siRNA targeted against the uidA gene. Down-regulation of uidA
      mRNA and GUS activity by siRNA was observed in mycelia that developed from the
      protoplasts. The down-regulation was transient and was not carried over to
      conidiation. We concluded that gene silencing by siRNA provides a relatively
      quick method for analysis of gene function in A. niger.

PMID- 18066688
TI  - Analysis of genes associated with retrotransposons in the rice genome.
AB  - Retrotransposons comprise a significant fraction of the rice genome. Despite
      their prevalence, the effects of retrotransposon insertions are not well
      understood, especially with regard to how they affect the expression of genes. In
      this study, we identified one-sixth of rice genes as being associated with
      retrotransposons, with insertions either in the gene itself or within its
      putative promoter region. Among genes with insertions in the promoter region, the
      likelihood of the gene being expressed was shown to be directly proportional to
      the distance of the retrotransposon from the translation start site. In addition,
      retrotransposon insertions in the transcribed region of the gene were found to be
      positively correlated with the presence of alternative splicing forms.
      Furthermore, preferential association of retrotransposon insertions with genes in
      several functional classes was identified. Some of the retrotransposons that are
      part of full-length cDNA (fl-cDNA) contribute splice sites and give rise to novel
      exons. Several interesting trends concerning the effects of retrotransposon
      insertions on gene expression were identified. Taken together, our data suggests
      that retrotransposon association with genes have a role in gene regulation. The
      data presented in this study provides a foundation for experimental studies to
      determine the role of retrotransposons in gene regulation.

PMID- 18066690
TI  - Laparoscopic Burch colposuspension after failed sub-urethral tape procedures: a
      retrospective audit.
AB  - Our objective was to evaluate the outcome of laparoscopic Burch colposuspension
      in women with recurrent stress urinary incontinence after failed primary sub
      urethral tape procedures. A total of 16 patients were identified, and their data
      from symptom-specific questionnaires, urodynamic studies and urogynaecological
      assessment were collected. At a median follow-up of 24.5 months, objective and
      subjective cure rates were 54.5% and 92.9%, respectively. Average satisfaction
      score regarding outcome after surgery was 9.3 on a rating scale from 0 to 10. All
      but one patient had symptoms of urge incontinence pre-operatively with 64.3%
      experiencing cure or improvement post-operatively. Voiding difficulties were
      observed in one patient, and post-operative urodynamics revealed a significant
      decrease in urinary flow rate (p < 0.05) but with no difference in urinary
      residuals or maximum urethral closure pressure. Severe peri-urethral fibrosis was
      identified in 62.5% of the patients. Laparoscopic Burch colposuspension is an
      effective and safe surgical option.

PMID- 18066689
TI  - Menstrual and reproductive factors in relation to mammographic density: the Study
      of Women's Health Across the Nation (SWAN).
AB  - Menstrual and reproductive factors may increase breast cancer risk through a
      pathway that includes increased mammographic density. We assessed whether known
      or suspected menstrual and reproductive breast cancer risk factors were cross
      sectionally associated with mammographic density, by measuring area of
      radiographic density and total breast area on mammograms from 801 participants in
      the Study of Women's Health Across the Nation (SWAN), a multi-ethnic cohort of
      pre- and early perimenopausal women. From multivariable linear regression, the
      following menstrual or reproductive factors were independently associated with
      percent mammographic density (area of dense breast/breast area): older age at
      menarche (beta=10.3, P<0.01, for >13 vs. <12 years), premenstrual cravings and
      bloating (beta=-3.36, P=0.02), younger age at first full-term birth (beta=-8.12,
      P<0.01 for <or=23 years versus no births), greater number of births (beta=-6.80,
      P<0.01 for >or=3 births versus no births), and premenopausal status (beta=3.78,
      P<0.01 versus early perimenopausal). Only number of births remained associated
      with percent density after adjustment for age, race/ethnicity, study site, body
      mass index (BMI), and smoking. In addition, stratified analyses revealed that the
      association with number of births was confined to women within the lowest BMI
      tertile (beta=-12.2, P<0.01 for >or=3 births versus no births). Our data support
      a mechanism for parity and breast cancer that involves mammographic density among
      pre- and early perimenopausal women that may be modified by body size.

PMID- 18066691
TI  - Seidel-Herzel model of human baroreflex in cardiorespiratory system with
      stochastic delays.
AB  - The stochastic versus deterministic solution of the Seidel-Herzel model
      describing the baroreceptor control loop (which regulates the short-time heart
      rate) are compared with the aim of exploring the heart rate variability. The
      deterministic model solutions are known to bifurcate from the stable to sustained
      oscillatory solutions if time delays in transfer of signals by sympathetic
      nervous system to the heart and vasculature are changed. Oscillations in the
      heart rate and blood pressure are physiologically crucial since they are
      recognized as Mayer waves. We test the role of delays of the sympathetic
      stimulation in reconstruction of the known features of the heart rate. It appears
      that realistic histograms and return plots are attainable if sympathetic time
      delays are stochastically perturbed, namely, we consider a perturbation by a
      white noise. Moreover, in the case of stochastic model the bifurcation points
      vanish and Mayer oscillations in heart period and blood pressure are observed for
      whole considered space of sympathetic time delays.

PMID- 18066692
TI  - Hypomethylation of hepatocyte nuclear factor-1beta (HNF-1beta) CpG island in
      clear cell carcinoma of the ovary.
AB  - Expression of hepatocyte nuclear factor-1beta (HNF-1beta) is significantly up
      regulated in ovarian clear cell carcinoma (CCC). The mechanism of up-regulation,
      however, remains unclear. It has been recognized that hypomethylation of specific
      gene promoters is involved in aberrant gene expression in carcinogenesis. In the
      present study, ovarian CCCs were examined whether there was a correlation between
      the methylation and expression status of HNF-1beta, using combined bisulfite
      restriction analysis (COBRA), bisulfite-sequencing and immunocyto/histochemistry.
      In 2 CCC cell lines, hypomethylation of HNF-1beta CpG island strongly correlated
      with HNF-1beta expression, at both the mRNA and protein levels. In archival
      surgical specimens, 20 of 20 CCCs were immunohistochemically positive for HNF
      1beta, whereas none of 20 serous adenocarcinomas (SAs) or 12 normal ovaries were
      positive for it. By COBRA, methylation of HNF-1beta CpG island was less
      frequently detected in CCCs (8 of 20, 40%) than SAs (18 of 20, 90%) or normal
      ovaries (12 of 12, 100%) (p < 0.01), which was confirmed by bisulfite-sequencing.
      In addition, HNF-1beta hypomethylation correlated with a high HNF-1beta
      immunostaining score in CCCs. These results strongly suggest that hypomethylation
      of the HNF-1beta CpG island participates in the HNF-1beta up-regulation in
      ovarian CCC.

PMID- 18066693
TI  - Distribution of mosquito (Diptera: Culicidae) species and Wolbachia
      (Rickettsiales: Rickettsiaceae) infections during the bird immigration season in
      Pathumthani province, central Thailand.
AB  - Mosquito distribution in the immigration bird-nested area, Pathumthani province,
      was investigated from August to December in 2006. Mosquitoes were collected by
      using CO2-baited Centers for Disease Control light traps in which dry ice was
      used as a source of CO2 to attract mosquitoes. Six traps were operated from 4
      p.m. until 7 a.m. on each study day. Four genera, which were Anopheles,
      Armigeres, Culex, and Mansonia with 14 species of mosquitoes were collected.
      Culex gelidus (13.94-59.41%) and Culex tritaeniorhynchus (32.87-70.30%) were most
      collected species in this area for every month. Other two species with moderate
      distribution in this area were Anopheles barbirostris (0.76-3.30%) and Mansonia
      uniformis (1.55-11.36%). Polymerase Chain Reactions were performed for testing
      Wolbachia infection in Cx. gelidus and Cx. tritaeniorhynchus only. Fifty-four
      percent (15/28 pools) of Cx. gelidus and none (0/20 pools) of Cx.
      tritaeniorhynchus were positive for Wolbachia infection. Wolbachia infection in
      other mosquito species collected in this and other areas need to be investigated
      to understand species and geographic variation of Wolbachia infection in
      mosquitoes in nature.

PMID- 18066695
TI  - The journey of the surgeon-hero.

PMID- 18066694
TI  - New developments in the objective assessment of cough.
AB  - A variety of different methods are available for measuring cough. In clinical
      practice and most clinical trials subjective reporting of cough is relied upon,
      using scoring systems or visual analog scores (VAS). Although these measures give
      an indication of patients' perceptions of the severity of the symptom, they may
      be unreliable because they are influenced by other factors such as mood,
      vigilance, and expectations. An objective measure of cough would therefore be a
      valuable tool. In the last decade advances in computer technology and the
      availability of portable digital sound recording devices have resulted in a
      resurgence of interest in developing ambulatory systems for recording cough. The
      ultimate goal is an automated detection system of use in the wide variety of
      conditions that cause cough. Multidisciplinary teams of researchers around the
      world are applying techniques such as neural networks, voice recognition models,
      and other signal processing techniques to this problem. The main challenge is
      achieving high sensitivity with good discrimination of noncough signals. For
      cough sound detection, this is confounded by both the variability of the
      acoustics of cough sounds within and between individuals and the amount and
      variety of speech sounds that must be discriminated. Significant progress is
      being made and it is likely that accurate automated objective monitoring systems
      will be available in the near future. These systems have the potential to change
      the way cough is measured in clinical practice and clinical trials, allowing a
      better understanding of the effect of existing and novel treatments on this
      troublesome symptom.

PMID- 18066696
TI  - Challenges in cardiac risk assessment in bariatric surgery patients.
AB  - Bariatric surgery has serious associated medical comorbidity and procedure
      related risks and is thus considered an intermediate- to high-risk noncardiac
      surgery. Most patients referred for bariatric surgery have a low or very low
      functional capacity, making cardiac risk assessment imperative. Stress
      echocardiography has a high negative predictive value and can avoid some of the
      table weight and torso diameter problems associated with myocardial perfusion
      imaging. Echocardiograph contrast agents improve the ability to identify
      endocardial borders and assess ventricular wall motion and may be used with
      stress and nonstress imaging protocols. Single photon emission computer
      tomography (SPECT) imaging with attenuation correction, combined supine and prone
      imaging, use of technetium isotope, and positron emission tomography (PET)
      imaging may all provide some advantage for myocardial perfusion imaging for the
      obese patient.

PMID- 18066698
TI  - An update: the operative experience in adrenal, pancreatic, and other less common
      endocrine diseases of U.S. general surgery residents.
AB  - BACKGROUND: A prior study that examined the operative experience of general
      surgery residents in endocrine surgery for the academic years 1986-1987 to 1993
      1994 found this training to be inadequate due to low operative volume. METHODS:
      To evaluate how the development of minimally invasive endocrine surgery might
      alter this outcome, we reviewed more recent data from the Resident Statistic
      Summaries (Report C) of the Residency Review Committee from 1994-1995 to 2003
      2004. RESULTS: The main outcome measures were total number of residents and
      programs and the volume and distribution of operations performed. For
      adrenalectomy, the average number of cases per resident was 1.46; for endocrine
      pancreas, the average was 0.14. The most common number of any of these procedures
      performed by U.S. graduates was zero. CONCLUSION: Reports from postgraduate
      training in laparoscopic or endocrine surgery suggest that these fellowships may
      provide the necessary additional operative experience.

PMID- 18066697
TI  - Influence of osteoporosis on fracture fixation--a systematic literature review.
AB  - The goal of our systematic literature search was to prove whether the
      experimentally shown influence of osteoporosis on fracture fixation could be
      confirmed in clinical studies. Despite significant effects in several studies,
      this is not supported by pooled data due to lack of accurate osteoporosis
      assessment and complication definitions. INTRODUCTION: The fact that osteoporosis
      causes fractures is well-known; the assumption that it aggravates their
      orthopaedic treatment has not been proven. The goal of our systematic literature
      search was to find out whether the experimentally proven influence of
      osteoporosis on fracture fixation could be confirmed in clinical studies.
      METHODS: A systematic electronic database search was performed identifying
      articles that evaluated complications after fracture fixation among patients
      suspected of having osteoporosis as measured by BMD or surrogates including Singh
      index or risk factors. To determine complications risks (relative risk within 95%
      confidence interval) data were pooled across studies, weighted by sample size and
      stratified by treatment type. RESULTS: Ten studies out of 77 randomized
      controlled trials (51 hip, 23 distal radius and three proximal humerus studies)
      and three systematic reviews finally met eligibility criteria. Despite
      significant differences of the relative complication risk between osteoporotic
      and non-osteoporotic patients in several studies, this could not be proven in the
      pooled data. CONCLUSIONS: In contrast to biomechanical evidence that local
      osteoporosis affects anchorage of implants, this could not be reproduced in
      clinical studies, due to the lack of accurate osteoporosis assessment, missing
      complication definitions and heterogeneous inclusion criteria in these studies.
      Prospective studies are required that address specifically the correlation
      between local bone status and the risk of fixation failure.

PMID- 18066699
TI  - Influence of sleeve gastrectomy on several experimental models of obesity:
      metabolic and hormonal implications.
AB  - BACKGROUND: Ghrelin is an important factor in the regulation of intake. Most
      ghrelin is synthesized in the gastric fundus, but this is not the only location.
      The aim of this experimental study was to analyze the effect of sleeve
      gastrectomy (removing fundus) on the volume of intake in four experimental models
      and determine how this relates to changes in weight, plasmatic levels of
      glycemia, ghrelin, GLP-1, and insulin. METHODS: Sleeve gastrectomy was performed
      on four experimental models: (1) non-obesity; (2) exogenous obesity caused by
      excessive calorie intake; (3) genetically determined obesity (Zucker rats); and
      (4) genetically determined obesity and type 2 diabetes mellitus (Zucker diabetic
      fatty; ZDF rats). Model 2 had a control group on which sleeve gastrectomy was not
      performed. RESULTS: In the non-obese group, there were few changes after
      intervention, but in model 2, sleeve gastrectomy led to normalization of weight
      and endocrine-metabolic parameters that were the same as those for non-obese
      rats. The exception was for GLP-1, which has an anorexigenic effect: GLP-1
      remained higher. In Zucker rats, sleeve gastrectomy had a slight effect on all
      parameters. In ZDF rats, sleeve gastrectomy led to a reduction in intake and a
      stabilization of weight. CONCLUSIONS: Sleeve gastrectomy is a very good option
      for exogenous obesity. Normalization of hormonal levels led us to find an
      extragastric ghrelin production.

PMID- 18066700
TI  - Asymmetric dimethylarginine and impaired cardiovascular healing.
AB  - Asymmetric dimethylarginine (ADMA) typically accumulates in the plasma of
      patients with chronic renal failure. Moreover, its plasma levels are raised in
      the presence of virtually all of the traditional cardiovascular risk factors.
      ADMA inhibits the three isoforms of nitric oxide (NO) synthase, thereby blunting
      the known cardioprotective effects of NO. Through its NO inhibitor actions, ADMA
      also exerts pro-apoptotic effects and suppresses progenitor cell mobilization,
      differentiation and function. Among patients with ischemic heart disease, low
      progenitor cell bioavailability and kidney dysfunction are emerging as strong
      predictors of death and recurrent cardiovascular events. We propose that patients
      with ischemic heart disease, kidney dysfunction, and high risk factor burden
      exhibit adverse cardiovascular outcomes, at least in part, through ADMA-mediated
      NO depression, enhanced apoptotic signalling, and reduced progenitor cell
      bioavailability, with consequent blunting of cardiovascular healing. Further
      research into the mechanisms that regulate the NO/ADMA balance may advance our
      understanding of cardiovascular diseases.

PMID- 18066701
TI  - Thrombosis of temporal artery and renal vein in Kimura-disease-related nephrotic
      syndrome.
AB  - Kimura disease (KD) is an angiolymphoid proliferative disorder of unknown
      etiology, occurs mainly in Asian patients, presenting with subcutaneous slowly
      growing masses, with a predilection for preauricular and submandibular regions.
      The clinical course of the disease is thought to be benign. Concomitant
      peripheral blood eosinophilia and elevated serum immunoglobulin E levels are
      often observed. Main systemic manifestation of the KD is renal involvement. Renal
      abnormalities, notably proteinuria and nephrotic syndrome have been found to be
      associated with KD. We report a 42-year-old man with KD and a steroid-sensitive
      membraneous nephrotic syndrome with bilaterally temporal artery and renal vein
      thrombosis. This is the first reported case of KD associated nephrotic syndrome
      complicated with wide arterial and venous thrombosis from Anatolia.

PMID- 18066702
TI  - Hydrogen as an energy source for the human pathogen Bilophila wadsworthia.
AB  - The gram-negative anaerobic gut bacterium Bilophila wadsworthia is the third most
      common isolate in perforated and gangrenous appendicitis, being also found in a
      variety of other infections. This organism performs a unique kind of anaerobic
      respiration in which taurine, a major organic solute in mammals, is used as a
      source of sulphite that serves as terminal acceptor for the electron transport
      chain. We show here that molecular hydrogen, one of the major products of
      fermentative bacteria in the colon, is an excellent growth substrate for B.
      wadsworthia. We have quantified the enzymatic activities associated with the
      oxidation of H(2), formate and pyruvate for cells obtained in different growth
      conditions. The cell extracts present high levels of hydrogenase activity, and up
      to five different hydrogenases can be expressed by this organism. One of the
      hydrogenases appears to be constitutive, whereas the others show differential
      expression in different growth conditions. Two of the hydrogenases are soluble
      and are recognised by antibodies against a [FeFe] hydrogenase of a sulphate
      reducing bacterium. One of these hydrogenases is specifically induced during
      fermentative growth on pyruvate. Another two hydrogenases are membrane-bound and
      show increased expression in cells grown with hydrogen. Further work should be
      carried out to reveal whether oxidation of hydrogen contributes to the virulence
      of B. wadsworthia.

PMID- 18066703
TI  - Isolated limb perfusion with melphalan and TNF-alpha in the treatment of
      extremity sarcoma.
AB  - Isolated limb perfusion (ILP) with chemotherapy alone has uniformly failed in the
      treatment of irresectable extremity soft tissue sarcomas. The addition of tumor
      necrosis factor-alpha (TNF-alpha) to this treatment approach contributed to a
      major step forward in the treatment of locally advanced extremity soft tissue
      sarcoma (STS). High response rates and limb salvage rates have been reported in
      multicenter trials, which combined ILP with TNF-alpha plus melphalan, which
      resulted in the approval of TNF-alpha for this indication in Europe in 1998.
      Subsequently a series of confirmatory single institution reports on the efficacy
      of the procedure have now been published. TNF-alpha has an early and a late
      effect; it enhances tumor-selective drug uptake during the perfusion and plays an
      essential role in the subsequent selective destruction of the tumor vasculature.
      These effects result in a high response rate in high-grade soft tissue sarcomas.
      This induction therapy thus allows for resection of tumor remnants some 3 months
      after ILP and thus avoidance of limb amputation. TNF-alpha-based ILP is a well
      established treatment to avoid amputations. It represents an important example of
      tumor vascularity-modulating combination therapy and should be offered in large
      volume tertiary referral centers.

PMID- 18066706
TI  - Larval host plant origin modifies the adult oviposition preference of the female
      European grapevine moth Lobesia botrana.
AB  - According to the 'natal habitat preference induction' (NHPI) hypothesis,
      phytophagous insect females should prefer to lay their eggs on the host species
      on which they developed as larvae. We tested whether this hypothesis applies to
      the breeding behaviour of polyphagous European grapevine moth, Lobesia botrana,
      an important pest in European vineyards. We previously found that different grape
      cultivars affect several life history traits of the moth. Because the different
      cultivars of grapes are suspected to provide different plant quality, we tested
      the NHPI hypothesis by examining oviposition choice of L. botrana among three
      Vitis vinifera cultivars (Pinot, Chasselas and Chardonnay). In a choice
      situation, females of L. botrana that had never experienced grapes were able to
      discriminate between different grape cultivars and preferentially selected Pinot
      as an oviposition substrate. This 'naive' preference of oviposition could be
      modified by larval environment: Females raised on grapes as larvae preferred to
      lay eggs on the cultivar that they had experienced. Furthermore, experience of
      the host plant during adult emergence could be excluded because when pupae
      originating from our synthetic diet were exposed to grapes, the emerging adults
      did not show preference for the cultivar from which they emerged. The NHPI
      hypothesis that includes the two sub-hypothesis "Hopkins host selection
      principle" and "chemical legacy" may thus be relevant in this system.

PMID- 18066707
TI  - Stress responses in yeasts: what rules apply?
AB  - Living organisms have evolved a complex network of mechanisms to face the
      unforeseen nutritional and environmental circumstances imposed on their natural
      habitats, commonly termed "stress". To learn more about these mechanisms, several
      challenges are usually applied in the laboratory, namely nutrient starvation,
      heat shock, dehydration, oxidative exposures, etc. Yeasts are chosen as
      convenient models for studying stress phenomena because of their simple cellular
      organization and the amenability to genetic analysis. A vast scientific
      literature has recently appeared on the defensive cellular responses to stress.
      However, this plethora of studies covers quite different experimental conditions,
      making any conclusions open to dispute. In fact, the term "yeast stress" is
      rather confusing, since the same treatment may be very stressful or irrelevant,
      depending on the yeast. Customary expressions such as "gentle stress" (non
      lethal) or "severe stress" (potentially lethal) should be precisely clarified. In
      turn, although prototypic yeasts share a common repertoire of signalling
      responsive pathways to stress, these are adapted to the specific ecological niche
      and biological activity of each particular species. What does "stress" really
      mean? Before we go any deeper, we have to define this uncertain meaning along
      with a proper explanation concerning the terms and conditions used in research on
      yeast stress.

PMID- 18066705
TI  - [Prehospital care of acute coronary syndrome by anaesthetists. Prospective
      comparison with the care standards of cardiologists].
AB  - BACKGROUND: Prehospital treatment of acute coronary syndrome (ACS) by
      anaesthetists acting in physician staffed emergency medical service (EMS) was
      compared with that of the gold standard of cardiologists. METHODS: Prospectively
      599 patients with assumed ACS were traced. Prehospital diagnosis and therapy were
      compared with re-evaluation of ECGs and diagnosis on hospital discharge. RESULTS:
      In the case of ST-segment elevating myocardial infarction (STEMI) anaesthetists
      diagnosed 84% of cases correctly and cardiologists in 94% (p=0.048). False
      positive diagnoses were given in 11% by anaesthetists versus 5% by cardiologists
      (p=0.31). Anaesthetists accompanied all patients with instable angina versus 94%
      by cardiologists (p=0.06). Anaesthetists achieved 82% of patients to be pain-free
      versus 73% of cardiologists (p=0.01). Mortality until discharge was identical for
      the two groups (8.2%). CONCLUSION: In prehospital management of ACS cardiologists
      showed higher diagnostic competence, whereas anaesthetists revealed a greater
      degree of therapeutic caution. Patient mortality was not influenced.

PMID- 18066708
TI  - Development of an optical RNA-based aptasensor for C-reactive protein.
AB  - The development of a RNA-aptamer-based optical biosensor (aptasensor) for C
      reactive protein (CRP) is reported. CRP is an important clinical biomarker; it
      was the first acute-phase protein to be discovered (1930) and is a sensitive
      systemic marker of inflammation and tissue damage. It has also a prognostic value
      for patients with acute coronary syndrome. The average concentration of CRP in
      serum is 0.8 ppm and it increases in response to a variety of inflammatory
      stimuli, such as trauma, tissue necrosis, infection and myocardial infarction.
      The interaction between the 44-base RNA aptamer and the target analyte CRP is
      studied. In particular, the influence of the aptamer immobilization procedure
      (chemistry, length, concentration), as well as the binding conditions, i.e., the
      influence on the binding of different buffers, the presence of Ca2+ ion and the
      specificity (against human serum albumin) have been evaluated. Using the best
      working conditions, we achieved a detection limit of 0.005 ppm, with good
      selectivity towards human serum albumin. Some preliminary experiments in serum
      are reported.

PMID- 18066710
TI  - Management of uterine giant myoma.
AB  - BACKGROUND: Giant myomas of the uterus are uncommon, particularly in developed
      countries. CASE: This report illustrates a case of a woman with a bilobated giant
      myoma of the uterus weighed in total 27.7 kg. The patient had an abdominal
      distension first noted 18 months before and the personal history evidenced
      difficulties in walking and tiredness. Abdominal hysterectomy and bilateral
      salpingo-oophorectomy were carried out. CONCLUSIONS: The knowledge of the
      different clinical manifestation of these myomas may allow to face that with
      adequate perioperative care, in order to assure a carefully and successfully
      surgery, although sometimes a benign pathology may be not easy to suspect in a
      first time.

PMID- 18066709
TI  - [Histopathology in liver transplantation].
AB  - Histopathology plays an important role in the diagnosis of graft complications
      following liver transplantation (LTX) and includes the diagnosis of underlying
      liver disease, assessment of the donor liver before LTX and control biopsies
      after LTX. Within the early period after LTX (time zero and first month)
      preservation/reperfusion injury, as well as hyperacute and acute rejection may
      occur. Surgical vascular or biliary complications can cause parenchymal
      morphological changes. Within 12 months following LTX, histological signs of
      opportunistic infections and chronic rejection are frequent findings and disease
      recurrence is typical beyond the first year. Drug toxicity in liver allograft
      recipients can be induced by immunosuppressive therapy or other drugs. A high
      percentage of adult patients reveal histological features of idiopathic chronic
      hepatitis 6 months after LTX. Histopathological differential diagnosis of the
      combined underlying causes or complications is often difficult.

PMID- 18066711
TI  - Artemether and tribendimidine lack activity in experimental treatment of
      Paragonimus westermani in the dog.
AB  - Artemether and tribendimidine are active against several trematode species, but
      no data are available regarding the lung fluke Paragonimus westermani. We
      infected six dogs with 100 P. westermani metacercariae each. At day 103 post
      infection, four dogs were treated orally for 3 days with either artemether (total
      dose, 66.7 and 75 mg/kg) or tribendimidine (total dose, 100 mg/kg). The remaining
      dogs were left untreated and served as control. Sixteen days after the final
      dosing, dogs were killed, and P. westermani flukes were recovered from the lungs
      and counted. Neither artemether nor tribendimidine showed activity against P.
      westermani at this dose regimen in dogs.

PMID- 18066712
TI  - Alteration of apoptotic signaling molecules as a function of time after radiation
      in human neuroblastoma cells.
AB  - Ascertaining the time-dependent regulation of induced apoptosis and
      radioresistance is important to understand the relationship between the level of
      spontaneous apoptosis in cells and their radiosensitivity. Accordingly, we
      investigated the time-dependent expression of apoptosis related genes and
      radioresistance in neuroblastoma cells. Serum-starved human SK-N-MC cells were
      exposed to low linear energy transfer (LET) radiation (2 Gy) and incubated for
      15, 30, 45 min, and 48 h. Radioresistance was investigated by examining the NF
      kappa B DNA-binding activity, cellular toxicity, DNA fragmentation, and
      expression of apoptotic signal transduction molecules. NF kappa B DNA binding
      activity was analyzed using electrophoretic mobility shift assay (EMSA). Cellular
      toxicity was measured using MTT assay. DNA fragmentation was quantified by
      labeling with fluorescein-conjugated deoxynucleotides. Microarray analysis was
      performed using cDNA microarray and relative gene expression was measured as %
      GAPDH and, subsequently validated using Q-PCR. Induction of NF kappa B analyzed
      using EMSA showed an increased DNA-binding activity at all time points
      investigated. Induced DNA fragmentation was observed after 15, 30, and 45 min
      post-radiation. Relatively, induced fragmentation was reduced after 48 h.
      Compared to the untreated controls cellular toxicity was induced with low LET
      radiation after 15, 30, and 45 min. Conversely, cytotoxicity was relatively less
      at 48 h after low LET radiation. Microarray analysis after low LET radiation
      revealed time-dependent modulation of apoptosis-related genes that are involved
      in radio-adaptation, spontaneous apoptosis-related early-responsive genes and
      late response genes. These results suggest that the time-dependent regulation of
      apoptotic response may determine the relationship between the level of
      spontaneous apoptosis in cells and their radiosensitivity.

PMID- 18066714
TI  - In vitro performance testing of the novel Medspray wet aerosol inhaler based on
      the principle of Rayleigh break-up.
AB  - PURPOSE: A new inhaler (Medspray) for pulmonary drug delivery based on the
      principle of Rayleigh break-up has been tested with three different spray nozzles
      (1.5; 2.0 and 2.5 mum) using aqueous 0.1% (w/w) salbutamol and 0.9% (w/w) sodium
      chloride solutions. MATERIALS AND METHODS: Particle size distributions in the
      aerosol were measured with the principles of time of flight (APS) and laser
      diffraction (LDA). RESULTS: The Medspray inhaler exhibits a highly constant
      droplet size distribution in the aerosol during dose emission. Droplets on the
      basis of Rayleigh break-up theory are monodisperse, but due to some coalescence
      the aerosols from the Medspray inhaler are slightly polydisperse. Mass median
      aerodynamic diameters at 60 l.min(-1) from APS are 1.42; 1.32 and 1.27 times the
      theoretical droplet diameters (TD's) and median laser diffraction diameters are
      1.29; 1.14 and 1.05 times TD for 1.5; 2.0 and 2.5 mum nozzles (TD: 2.84; 3.78 and
      4.73 mum respectively). CONCLUSIONS: The narrow particle size distribution in the
      aerosol from the Medspray is highly reproducible for the range of flow rates from
      30 to 60 l.min(-1). The mass median aerodynamic droplet diameter can be well
      controlled within the size range from 4 to 6 mum at 60 l.min(-1).

PMID- 18066713
TI  - Mono ADP-ribosylation inhibitors prevent inflammatory cytokine release in
      alveolar epithelial cells.
AB  - A549, a type II alveolar epithelial cell line stimulated with LPS (10 mug/ml),
      released high levels of the inflammatory cytokines IL-6 and IL-8. Here, we have
      investigated whether ADP-ribosylation inhibitors block the LPS-triggered cytokine
      release in epithelial cells. When coincubating A549 with LPS and meta
      iodobenzylguanidine or novobiocin, selective arginine-dependent ART-inhibitors,
      the release of IL-6 and IL-8 was inhibited in a concentration-dependent manner.
      This effect has been linked with the presence of a functionally active arginine
      ADP-ribosylating enzyme on the cell surface. To this aim, we amplified by RT-PCR
      the ART1 transcript and identified four ADP-ribosylated proteins likely substrate
      for ART1. The mechanism behind the cytokine inhibition in epithelial cells seems
      to be correlated with the presence of ART1, which behaves as an essential
      positive regulator of inflammatory cytokines. This novel observation indicates
      this enzyme as well as other novobiocin/MIBG sensitive ARTs as potential targets
      for the development of new therapeutic strategies.

PMID- 18066715
TI  - Changes in perceived health and depressive symptoms: a longitudinal analysis with
      older Korean Americans.
AB  - The present study examined changes in the perceived health of older Korean
      Americans (n = 141) over a 2-year period: 2003 (T1) and 2005 (T2). A hierarchical
      regression model of changes in perceived health was estimated with the following
      array of predictors: (1) background variables (age, gender, marital status,
      education, and length of stay in the United States), (2) initial perceived health
      (T1), (3) physical and mental health conditions at T1 (chronic conditions,
      functional disability, and depressive symptoms), and (4) changes in physical and
      mental health conditions (T2 - T1). When the effects of background variables and
      baseline perceived health were controlled, baseline chronic conditions and
      changes in both chronic conditions and depressive symptoms were found to predict
      changes in perceived health. Older individuals who initially had more chronic
      conditions and those who had experienced an increasing number of chronic
      conditions and depressive symptoms over 2 years viewed their health more
      negatively at follow-up. Findings highlight the importance of interventions for
      disease management and mental health promotion to enhance subjective health among
      older Korean immigrants.

PMID- 18066716
TI  - Acculturation matters: risk perceptions of smoking among Bosnian refugees living
      in the United States.
AB  - The relationship between acculturation and health behavior change is complex.
      Little research has focused on acculturation and perceptions of health-related
      risks. This study investigated acculturation and risk perceptions of heart attack
      and lung cancer among a group of refugees. Questionnaires were distributed to a
      sample of Bosnian refugees living in the United States (N = 55). Results
      indicated that smokers thought they were less at risk than other smokers and no
      more at risk than non-smokers, whereas non-smokers did not think they were less
      at risk than other non-smokers. Greater acculturation was associated with greater
      perception of smokers' risk of heart attack and lung cancer. Smoking cessation
      interventions with refugees should incorporate culturally appropriate risk
      information.

PMID- 18066717
TI  - Correlates of resilience in the face of adversity for Korean women immigrating to
      the US.
AB  - OBJECTIVES: To explore the association between resilience and psychosocial
      variables of theoretical relevance such as self-esteem, optimism, religiousness,
      cultural interdependency, and belief in higher education in a population of
      elderly Korean women and their daughters who experienced great adversity.
      METHODS: Surveys were conducted with 200 elderly Korean women and 170 of their
      daughters in several community locations. RESULTS: Both mothers and daughters
      experienced great adversities in their lives such as psychological and physical
      losses from war as well as current and past difficulties with relocation. The
      mothers' bivariate correlations indicate that self-esteem, optimism,
      religiousness, and cultural interdependency were significantly correlated with
      resilience. Length of time in the US, age entering the US, physical and
      psychological war-related adversities, current relocation difficulties, self
      esteem, optimism, cultural interdependency, and belief in education were all
      significantly associated with daughters' resilience. In linear regression, self
      esteem and optimism were significant predictors of resilience in both mothers and
      daughters. CONCLUSIONS: Self-esteem and optimism deserve further attention as
      psychological factors that may increase the likelihood of developing resilience.
      Implications of these findings for health professionals are discussed.

PMID- 18066720
TI  - [Neuropsychological profile of childhood-onset obsessive-compulsive disorder].
AB  - In this review paper, studies focusing on the neuropsychological characteristics
      of childhood-onset obsessive-compulsive disorder (OCD) were evaluated. The
      literature search covered the MedLine and PsycInfo databases through June 2006.
      The presented results are of those that focus on the processes of attention,
      memory, and executive functions related to the aspects of the measured
      instruments used. The aim of this review was to provide a general
      neuropsychological profile of childhood-onset OCD based on the reviewed studies.
      In general, results showed that there is no clear evidence that the
      neuropsychological aspects of childhood-onset OCD differ from those of adult
      onset OCD. In parallel with this, the processes of attention and memory in OCD
      are observed to be selective and biased, and this bias is directed towards threat
      relevant stimuli related to obsessions and compulsions. In addition, dysfunction
      in memory and visuospatial processes in OCD patients do not result from memory
      impairment per se, but rather from an impaired ability to apply efficiently
      elaborated strategies. In childhood-onset OCD, the various lines of evidence
      consistently include impairment of response suppression and motor inhibition
      abilities; there is less consistent evidence for reduced set shifting, fluency,
      conceptual thinking, and planning ability. Whereas clinical observation suggests
      that a central problem in OCD is at the meta-memory level and that people with
      OCD have less meta-cognitive ability, processing of meta-cognition in childhood
      onset OCD has not been investigated adequately. Finally, the results of the
      reviewed studies were evaluated in terms of the effects of basic co-morbidity,
      such as depression, Tourette's disorder, tic disorder, and other confounding
      variables.

PMID- 18066718
TI  - Imported compounded diet pill use among Brazilian women immigrants in the United
      States.
AB  - In Brazil, compounded diet pills that combine amphetamines, benzodiazepines,
      antidepressants, diuretics and laxatives are often prescribed. In 2006, the Food
      and Drug Administration banned their sale in the United States (US) citing
      substantial safety concerns. This study evaluates the prevalence of, and factors
      associated with, use of these pills among Brazilian immigrant women aged 18-50.
      Pill use was assessed at one clinic and two churches using an anonymous survey (n
      = 307). While living in the US, 18% of clinic respondents and 9% of church
      respondents reported using these diet pills. Nearly two thirds of pill users
      reported adverse effects. In multivariate logistic regression analysis, being
      unmarried, college educated, dissatisfied with current weight, and advised by a
      US physician to lose weight were associated with greater odds of imported diet
      pill use. To enhance care of Brazilian immigrants, US physicians should become
      familiar with the health consequences of imported diet pills from Brazil.

PMID- 18066721
TI  - [The effect of permanent ostomy on body image, self-esteem, marital adjustment,
      and sexual functioning].
AB  - OBJECTIVE: The aim of this study was to investigate the effects of permanent
      ostomy on body image, sexual functioning, self-esteem, and marital adjustment.
      METHOD: SCID-I outpatient forms were administered to 52 subsequent patients that
      underwent permanent colostomy or ileostomy operations, and 40 of them that did
      not fit any of the diagnostic criteria for psychiatric disorders were then
      administered a sociodemographic data questionnaire, and the Body Image Scale,
      Rosenberg Self-Esteem Scale, Dyadic Adjustment Scale, and Golombok Rust Sexual
      Functions scale. The control group consisted of 20 age- and gender-matched
      healthy volunteers. RESULTS: Body Image, Rosenberg Self-Esteem, and Dyadic
      Adjustment Scale scores were higher in permanent ostomy patients compared to
      controls, indicating more ostomy-related disturbance. Sexual functions were found
      to be impaired as well, except impotence and rapid ejaculation parameters.
      Complaints of anorgasmia were more frequent among female colostomy patients. Body
      image, and the touch, communication, and frequency parameters of sexual
      functioning were less disturbed in male patients than in females. Female patients
      with a psychiatric history experienced vaginismus problems more frequently.
      Patients with a history early childhood separation from parents had lower self
      esteem scores and more frequently avoided sexual activity. Following ostomy
      surgery, the frequency of male impotence decreased over time. CONCLUSION:
      Permanent ostomy causes impairment in perceived body image, dyadic adjustment,
      and sexual functioning.

PMID- 18066722
TI  - [Is there gender difference in infertile couples with no axis one psychiatric
      disorder in context of emotional symptoms, social support and sexual function?].
AB  - OBJECTIVE: It was aimed to evaluate the levels of emotional distress, social
      support and sexual function of infertile couples with no psychiatric Axis-I
      disorder according to gender differences. METHOD: The study sample of 103 primary
      infertile couples with no psychiatric Axis-I disorder according to DSM-IV were
      given Beck Depression Inventory, State and Trait Anxiety Inventory, Inventory of
      Perceived Social Support and Golombok Rust Inventory of Sexual Satisfaction
      (GRISS). RESULTS: The sample's depressive symptom severity did not indicate
      clinical depression, state anxiety was within normal range, and trait anxiety was
      high according to the scales. Compared to men, women had more severe depressive
      symptoms when they were the cause of couple's infertility whether alone or with
      their husbands, and higher trait anxiety in all infertility groups, and more
      perceived social support of family whether they or their husbands are the cause
      of infertility. According to sexual functioning profile obtained by the subscale
      scores of GRISS, more frequently defined problems of sexual relationship were non
      communication and non-sensuality for men and avoidance for women in all
      infertility groups. The emotional distress of woman and man were correlated
      negatively with their perceived social support and positively with their sexual
      functioning. CONCLUSION: It was concluded that women had more social support and
      emotional distress and men had more problems of sexual function, however,
      satisfactory social support might decrease the emotional symptoms of both
      genders.

PMID- 18066723
TI  - [The association between disability and residual symptoms in depressive patients:
      a 3-month follow-up].
AB  - OBJECTIVE: In this 3-month naturalistic follow-up we aimed to investigate
      depression treatment outcome and the correlation between improvement of
      depressive symptoms and level of disability. METHOD: The study included 104
      patients with depression that presented to the Hacettepe Psychiatry Outpatient
      Clinic. The course was defined operationally using the Hamilton Depression Rating
      Scale, Hamilton Anxiety Rating Scale, and Structured Clinical Interview for DSM
      IV Axis I Disorders. The World Health Organization Disability Assessment Schedule
      (WHO-DAS II) was administered to determine level of disability. Patients received
      follow-up assessments using the same instruments 3 months after receiving
      antidepressant treatment. RESULTS: Follow-up assessments showed that improvement
      in Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale total
      scores was statistically significant, and lower anxiety and depression ratings
      were correlated with lower disability levels. The patients that had severe
      depression and anxiety at the beginning of the course had residual depressive
      symptoms. The results showed that severity of depression was a predictor of
      residual symptoms in our cohort. Psychological anxiety was the most common
      residual symptom (consistent with other studies) and the patients with a
      psychological anxiety score > or = 2 had higher disability levels (Z = -3.570, P
      < 0.05). CONCLUSION: Severity of depression was a predictor of residual symptoms
      and partial remission after a depressive episode appeared to be strongly
      associated with disability. These findings highlight the importance of adequate
      treatment of depression.

PMID- 18066724
TI  - [The relationship between the dimensions of alexithymia and the intensity of
      depression and anxiety].
AB  - OBJECTIVE: The aim of the present study was to underline the multidimensional
      nature of alexithymia, and to examine the relationship between these dimensions
      and the intensity of depression and anxiety symptoms. METHOD: The study included
      145 undergraduate students that were administered 4 self-report instruments,
      including the Toronto Alexithymia Scale (TAS), Beck Anxiety Inventory (BAI), Beck
      Depression Inventory (BDI), and Positive and Negative Affect Schedule (PANAS).
      RESULTS: In accordance with the aim of the study, due to the increased number of
      items and relative strength of the psychometric characteristics of the subscales,
      the 26-item version of the Toronto Alexithymia Scale (TAS-26) was used. Following
      the factor analysis run for TAS, 3 dimensions with high internal consistency
      coefficients were obtained: 1. Difficulty in communicating feelings; 2.
      Difficulty in recognizing and identifying feelings; 3. Lacking in imaginative
      capacity. Hierarchical regression analyses indicated that the intensity of
      depressive symptoms was only related to an increase in the difficulty in
      communicating feelings; on the other hand the intensity of anxiety symptoms was
      related to an increase in difficulty in recognizing and identifying feelings and
      also conversely to depression symptoms, the intensity of anxiety symptoms was
      found to be related a decrease in the difficulty in communicating feelings
      dimension of alexithymia. CONCLUSION: This study not only addressed the
      multidimensional nature of alexithymia, but also suggests further studies to
      consider alexithymia as a discriminating factor between depression and anxiety
      symptoms. According to the study, while people who have intensive depressive
      symptoms have difficulty in communicating their feelings, people who have anxiety
      symptoms tend to communicate more their feelings. In addition, the intensity of
      anxiety is positively related to difficulty in recognizing and identifying
      feelings. Another words, anxious people tend to have difficulty in recognizing
      and identifying their feelings. These findings of the study are discussed in
      light of the literature.

PMID- 18066725
TI  - [Development of a questionnaire to assess inter-episode functioning in bipolar
      disorder: Bipolar Disorder Functioning Questionnaire].
AB  - OBJECTIVE: Even though quality of life and functioning are topics that are point
      of interest, they are not assessed adequately in mood disorders. In this study,
      it is aimed to develop a functioning assessment scale in bipolar disorder.
      METHOD: Bipolar Disorder Functioning Questionnaire (BDFQ) is developed by the
      Scientific Section for Mood Disorders of the Psychiatric Association of Turkey.
      The questionnaire contains 58 items, and consists of eleven subscales: emotional
      functioning, intellectual functioning, sexual functioning, feelings of
      stigmatization, social withdrawal, household relations, relations with friends,
      participation to social activities, daily activities and hobbies, taking
      initiative and self sufficiency, and occupation. RESULTS: In this study, 252
      remitted bipolar patients from 15 centers were included. In addition, thirty
      subjects without any lifetime psychiatric, neurological or physical disease were
      recruited. The mean age of the patients was 38.6+/-12.1 and 56% (n=141) were
      female. The mean duration of the bipolar disorder was 11.9+/-9.2 years, and 91.3%
      of the patients were diagnosed to have bipolar I disorder. In the reliability
      analyses, after the exclusion of six items with low reliability coefficients, The
      Cronbach alpha coefficient was calculated to be 0.91. The item-total scale
      correlations were between 0.22-0.86. In test-retest reliability, the correlation
      between the two ratings was high (r=0.82, p<0.0001). In validity analyses, 13
      factors were obtained representing 65.1% of the total variance in exploratory
      factor analysis. In confirmatory factor analysis, 11 domains fit the model with a
      RMSEA of 0.061. BDFQ significantly correlated with GAF (r=0.428, p<.0001). BDFQ
      also showed significantly negative correlation with HAM-D (r=-0.541, p<0.0001)
      and YMRS (r=-0.365, p<0.0001). It discriminated the patients (mean score=111.8+/
      15.2) from the healthy subjects (mean score=121.4+/-10.4) well (t=-2.300,
      p=0.038). CONCLUSION: With the six items excluded, it is suggested that the 52
      item BDFQ is a reliable and valid instrument in the assessment of functioning in
      bipolar disorder.

PMID- 18066726
TI  - [The validity and reliability of the Turkish Pediatric Quality of Life Inventory
      for children 13-18 years old].
AB  - OBJECTIVE: The Pediatric Quality of Life Inventory (PedsQL) is a modular
      instrument that measures health related quality of life, and investigates the
      physical and psychosocial functioning, unrelated to health, of children 2-18
      years old. In this study, the objective was to evaluate the validity and
      reliability of the Turkish PedsQL in adolescents 13-18 years old. METHOD: The
      study included 230 adolescents and 230 parents. The subjects were separated into
      3 groups: 1. Healthy; 2. Has an acute disease; 3. Has a chronic disease. The
      reliability and the validity of PedsQL were computed. RESULTS: The internal
      consistency of the scale (Cronbach's alpha coefficient) was 0.82 for the child
      self-report and 0.87 for the parent proxy report. The PedsQL scores of both the
      child self-report and parent proxy report showed a statistically significant low
      to medium level of inversely proportional correlation with many indicators of
      morbidity and illness burden. There was a statistically significant and direct
      proportional correlation between the child self-report and parent proxy report
      scores. CONCLUSION: The PedsQL is valid and reliable for evaluating the quality
      of life of Turkish adolescents 13-18 years old.

PMID- 18066727
TI  - [The mechanisms of action of antipsychotic drugs: is atypicality superior in
      schizophrenia treatment?].
AB  - This review presents the mechanisms of action of typical and atypical
      antipsychotic drugs, emphasizing the differences in the pharmacology of these
      drugs used in the treatment of schizophrenia. Initially, the concept of
      atypicality will be examined through the 2 most widely accepted hypotheses.
      Hypotheses concerning a high serotonin 5HT2A/dopamine D2 receptor antagonism
      ratio and a special interaction with D2 receptors via mesolimbic selectivity or a
      weaker blockade will be discussed. Next, the mechanisms of action of typical and
      atypical antipsychotics will be explored at the receptor level. Receptor activity
      of atypical antipsychotics other than D2 receptors at 5HT2A, 5HT2C, 5HT1A, and
      adrenergic alpha1 and alpha2, along with relevant, currently important, and
      consistent findings, and other mechanisms of action, such as glutamate modulation
      and increased prefrontal cortical acetylcholine release will be reviewed. In the
      final section, some specific mechanisms of action, which might be related to
      clozapine's superiority in schizophrenia treatment, will be examined. Atypical
      antipsychotics provide a variety of mechanisms of action as compared to typical
      antipsychotics, and they might be efficacious in treating symptom domains other
      than positive symptoms. In clinical practice, the superiority of atypical
      antipsychotics other than clozapine remains an issue that needs to be proven.

PMID- 18066728
TI  - [Gilles de la Tourette syndrome mimicking an eating disorder].
AB  - Vomiting and retching are behaviours that are part of the clinical manifestation
      of several disorders. Rarely, vomiting is actually tic and, when not recognized,
      may mislead physicians and other caregivers to erroneously diagnose a medical or
      psychiatric disorder without considering a tic-disorder. We report on an 18 year
      old male patient who demonstrated vomiting as main symptom. Initially, he was
      diagnosed with an eating disorder, bulimia nervosa purging type (DSM-IV TR).
      Firstly, he was not very able to suppress his vomiting, but later the vomiting
      became forced by putting fingers in his throat. This self-induced vomiting had a
      compulsive component and was performed after almost every meal. Psychiatric
      assessment disclosed a specific sequence of a premonitory epigastric feeling
      preceding the vomiting and relief after vomiting. History taking revealed that he
      had a childhood onset of motor tics (copropraxia which consisted of grabbing his
      genitalia, bilateral facial grimacing and sudden movements of the head) and
      phonic tics (sniffing and gargling). Furthermore, he had been treated with
      methylphenidate for a childhood diagnosis of Attention Deficit and Hyperactivity
      Disorder and suffered from obsessive-compulsive symptoms (OCS). His vomiting was
      considered a tic in the course of a Tourette syndrome. His score on the Yale
      Global Tic Severity Scale dropped from 74 at the first assessment to a score of
      50 at week 4 of treatment with risperidone 0,5 mg/day and sertralin 25 mg/day.
      Sedation and sexual dysfunction occurred as adverse events. Vomiting as a tic is
      rare clinical manifestation, but this possibility should be considered when
      patients have a history of tics.

PMID- 18066729
TI  - Differential effects of tributyltin and copper antifoulants on recruitment of non
      indigenous species.
AB  - Maritime transport is a primary vector for many marine invaders. For the past two
      decades, most commercial vessels have used tributyltin (TBT) antifouling (AF)
      paint, whereas recreational vessels have been restricted to alternatives, most
      commonly containing copper. Settlement plates painted with a collar of copper or
      TBT AF paint, and unpainted control plates, were deployed in commercial and
      recreational embayments in Port Jackson, Australia, and sampled photographically
      after 5 and 10 months. Copper enhanced early recruitment of several non
      indigenous species (NIS), whereas recruitment of indigenous species was typically
      reduced by copper. TBT limited the recruitment of NIS for just 5 months and
      indigenous species, for the entire study. The results suggest that the use of
      toxic AF paints, and the possible accumulation of AF biocides in embayments, may
      be negatively affecting indigenous epibiota. Conversely, copper antifoulants on
      recreational vessels may be facilitating the transport and establishment of
      copper tolerant NIS into disturbed estuarine habitats.

PMID- 18066730
TI  - Attachment point theory revisited: the fouling response to a microtextured
      matrix.
AB  - This paper examines attachment point theory in detail by testing the fouling
      attachment of several fouling groups to a microtextured matrix. Static bioassays
      were conducted on polycarbonate plates with nine equal regions, comprising eight
      scales of microtexture (4-512 microm) and one untextured region. The
      microtextures examined were continuous sinusoidal ridges and troughs of defined
      height and width. Attachment over the microtextured plates was examined for the
      diatom Amphora sp., the green alga Ulva rigida, the red alga Centroceras
      clavulatum, the serpulid tube worm Hydroides elegans and the bryozoan Bugula
      neritina. It was found that the size of the microtexture in relation to the size
      of the settling propagules/larvae was important in the selection of attachment
      sites. Attachment was generally lower when the microtexture wavelength was
      slightly smaller than the width of the settling propagules/larvae and increased
      when the wavelength was wider than their width. The effect of attachment points
      was weak for small motile microfoulers (Amphora sp. and U. rigida) (7 microm),
      strong for large macrofouling larvae (H. elegans and B. neritina) (129-321
      microm) and non-existent for the non-motile algal spores (C. clavulatum) (37
      microm). This study reinforces the potential of using attachment points to
      develop surfaces with increased fouling resistance or, alternatively, surfaces
      which promote the attachment of selected target sizes of motile propagules or
      larvae.

PMID- 18066731
TI  - Gesture imitation in autism. II. Symbolic gestures and pantomimed object use.
AB  - We report an experimental study of imitation of two types of meaningful gestures:
      (a) social-communicative gestures, and (b) pantomimed actions with objects
      (including counterfunctional object use) by children and adolescents with autism.
      Controls were (a) children with nonautistic developmental delays, matched for
      chronological age and receptive language age, and (b) typically developing
      children matched for receptive language. Children in both comparison groups
      imitated actions more accurately than did children with autism, who nonetheless
      demonstrated understanding of the meaning of the gestures. However, the autistic
      group tended to have difficulty naming gestures and also was less able than
      controls to produce actions on verbal request. Children with lower levels of
      language ability, including those with autism, had difficulty imitating
      unconventional use of objects, instead using the object for their conventional
      functions. The discussion addresses the implications of these results and our own
      previous related findings for representational and executive accounts of praxic
      deficits in autistic spectrum disorders.

PMID- 18066732
TI  - Impairments in part-whole representations of objects in two cases of integrative
      visual agnosia.
AB  - How complex multipart visual objects are represented perceptually remains a
      subject of ongoing investigation. One source of evidence that has been used to
      shed light on this issue comes from the study of individuals who fail to
      integrate disparate parts of visual objects. This study reports a series of
      experiments that examine the ability of two such patients with this form of
      agnosia (integrative agnosia; IA), S.M. and C.R., to discriminate and categorize
      exemplars of a rich set of novel objects, "Fribbles", whose visual similarity
      (number of shared parts) and category membership (shared overall shape) can be
      manipulated. Both patients performed increasingly poorly as the number of parts
      required for differentiating one Fribble from another increased. Both patients
      were also impaired at determining when two Fribbles belonged in the same
      category, a process that relies on abstracting spatial relations between parts.
      C.R., the less impaired of the two, but not S.M., eventually learned to
      categorize the Fribbles but required substantially more training than normal
      perceivers. S.M.'s failure is not attributable to a problem in learning to use a
      label for identification nor is it obviously attributable to a visual memory
      deficit. Rather, the findings indicate that, although the patients may be able to
      represent a small number of parts independently, in order to represent multipart
      images, the parts need to be integrated or chunked into a coherent whole. It is
      this integrative process that is impaired in IA and appears to play a critical
      role in the normal object recognition of complex images.

PMID- 18066733
TI  - Interactions between perception and action programming: evidence from visual
      extinction and optic ataxia.
AB  - We report a series of 7 experiments examining the interaction between visual
      perception and action programming, contrasting 2 neuropsychological cases: a case
      of visual extinction and a case with extinction and optic ataxia. The patients
      had to make pointing responses to left and right locations, whilst identifying
      briefly presented shapes. Different patterns of performance emerged with the two
      cases. The patient with "pure" extinction (i.e., extinction without optic ataxia)
      showed dramatic effects of action programming on perceptual report. Programming
      an action to the ipsilesional side increased extinction (on 2-item trials) and
      tended to induce neglect (on 1-item trials); this was ameliorated when the action
      was programmed to the contralesional side. Separable effects of using the
      contralesional hand and pointing to the contralesional side were apparent. In
      contrast, the optic ataxic patient showed few effects of congruency between the
      visual stimulus and the action, but extinction when an action was programmed.
      This effect was particularly marked when actions had to be made to peripheral
      locations, suggesting that it reflected reduced resources to stimuli. These
      effects all occurred using stimulus exposures that were completed well before
      actions were effected. The data demonstrate interactions between action
      programming and visual perception. Programming an action to the affected side
      with the contralesional limb reduces "pure" extinction because attention is
      coupled to the end point of the action. However, in a patient with deficient
      visuo-motor coupling (optic ataxia), programming an action can increase a spatial
      deficit by recruiting resources away from perceptual processing. The implications
      for models of perception and action are discussed.

PMID- 18066734
TI  - A time to think: circadian rhythms in human cognition.
AB  - Although peaks and troughs in cognitive performance characterize our daily
      functioning, time-of-day fluctuations remain marginally considered in the domain
      of cognitive psychology and neuropsychology. Here, we attempt to summarize
      studies looking at the effects of sleep pressure, circadian variations, and
      chronotype on cognitive functioning in healthy subjects. The picture that emerges
      from this assessment is that beyond physiological variables, time-of-day
      modulations affect performance on a wide range of cognitive tasks measuring
      attentional capacities, executive functioning, and memory. These performance
      fluctuations are also contingent upon the chronotype, which reflects
      interindividual differences in circadian preference, and particularly upon the
      synchronicity between the individuals' peak periods of circadian arousal and the
      time of the day at which testing occurs. In themselves, these conclusions should
      direct both the clinician's and the researcher's attention towards the utmost
      importance to account for time-of-day parameters when assessing cognitive
      performance in patients and healthy volunteers.

PMID- 18066735
TI  - 'What really annoys me is people take it like it's a disability', epilepsy,
      disability and identity among people of Pakistani origin living in the UK.
AB  - This paper reports on a study of Pakistani people with epilepsy. It explores
      their attitudes towards their condition, others' attitudes, its impact on their
      lives, and the extent to which they considered themselves as disabled. Epilepsy
      was variously interpreted within biomedical, folk and religious paradigms. In
      line with popular understandings, participants associated disability with stable,
      permanent and visible physical impairments and did not consider themselves as
      disabled. However, they also recognised a social dimension to their experience.
      Much of the distress and disadvantage they experienced was socially determined,
      both through direct prejudice and discrimination, and indirectly through a fear
      of others' negative reactions. However, the invisible and unpredictable nature of
      epilepsy meant that they could conceal their condition and thereby mitigate its
      social effects. 'Disability' was not experienced as a static and permanent state
      but as a potential identity that was both contingent and contested. The
      literature portrays people moving from biomedical to social interpretations of
      disability. However, the tensions experienced by people in the study were more
      between competing religious interpretations of their condition and, to some
      extent, between religious and medical approaches. Conceptions of disability,
      which are presented in the literature as antagonistic and mutually exclusive,
      were experienced as different dimensions reflecting the complexity of experience.
      The paper concludes by suggesting that for many people, for whom disability is an
      ambiguous, contingent and contested identity, public self-identification as
      disabled is an unrealistic goal. Rather than conceiving of disability as
      primarily physical or primarily social, it would be better construed as a complex
      interweaving of multiple factors--physical, environmental, socio-cultural and
      psychological factors.

PMID- 18066736
TI  - Socioeconomic status and diabetes among urban Indigenous Australians aged 15-64
      years in the DRUID study.
AB  - BACKGROUND: Diabetes is associated with lower socioeconomic status (SES) in
      developed countries, but the reverse is true in developing countries. Little is
      known about the relationship between SES and diabetes among Indigenous
      populations in developed countries. DESIGN: We examined the relationship between
      measures of SES and the prevalence of diabetes in the DRUID Study, a cross
      sectional study of urban Indigenous Australian volunteers in the Darwin region.
      RESULTS: Among 777 participants aged 15-64 years included in the analysis, 17.1%
      had diabetes, ranging from 2.0% among those aged 15-24 years to 50.8% of those
      aged 55-64 years. After adjusting for age and sex, diabetes was significantly
      more common among those of lower SES, whether measured by housing tenure,
      household income, or employment status. For example, compared with those living
      in a household that was owned/being purchased by its occupants, the relative odds
      of diabetes was 2.66 (95% confidence interval 1.71-4.15) for those living in
      rented/other accommodation. The inverse relationship between SES and diabetes was
      present even among those who had not previously been diagnosed with diabetes. The
      relationship between disadvantage and diabetes was not mediated to any great
      degree by obesity. CONCLUSIONS: The relationship between SES and diabetes among
      Indigenous Australians in this study is consistent with the patterns observed in
      developed countries, rather than those in some developing countries.

PMID- 18066737
TI  - Community stakeholders' perspectives on the impact of the minority AIDS
      initiative in strengthening HIV prevention capacity in four communities.
AB  - OBJECTIVE: The Minority AIDS Initiative (MAI) was launched in 1998 to address the
      disproportionate rates of human immunodeficiency virus/acquired immunodeficiency
      syndrome (HIV/AIDS) among racial and ethnic minorities in the United States. The
      Centers for Disease Control and Prevention (CDC) conducted an evaluation to
      assess the influence of MAI in four communities, and the extent to which these
      communities increased their capacity to meet the HIV prevention needs of racial
      and ethnic minorities. DESIGN: Retrospective data were collected annually through
      individual interviews over three years. Individual interviews were conducted with
      community stakeholders across the three waves of data collection. Data were
      analyzed using standardized qualitative methods including codebook development,
      coding, inter-coder agreement assessments, and data interpretation. This paper
      will highlight one area of inquiry - community stakeholders' perceptions of the
      impact of MAI in their communities. RESULTS: Community stakeholders reported that
      MAI increased capacity to respond to the HIV epidemic and provide services to
      racial and ethnic minorities. Specifically, MAI was perceived to have increased
      community empowerment, involvement, and awareness of HIV/AIDS; expanded HIV
      related services and organizational self-sufficiency; and improved collaboration
      and the coordination of services in the community. Although recognizing MAI gave
      national focus to the impact of the epidemic on minority communities, respondents
      raised concerns about the implementation process and the lack of sustainability
      planning. CONCLUSION: MAI represented an initial national attempt to address the
      disproportionate rates of HIV/AIDS among racial and ethnic minorities. However,
      other strategies are also needed to address these significant health disparities.
      At CDC, steps are currently underway to develop a comprehensive strategy to
      prevent and reduce the burden of HIV/AIDS among racial and ethnic minorities. As
      community stakeholders are critical partners in the effort to prevent the spread
      of HIV, strengthening their capacity and promoting their involvement can help
      combat the epidemic.

PMID- 18066738
TI  - Sexual health knowledge, attitudes and behaviours: variations among a religiously
      diverse sample of young people in London, UK.
AB  - OBJECTIVE: To report young people's variations in sexual health knowledge,
      attitudes and behaviours by religious affiliation. DESIGN: A cross-sectional,
      questionnaire-based survey administered in 16 Secondary/High schools in London,
      UK. The sample consisted of 3007 students in school Years 11-13 (aged 15-18),
      present in school on the day of questionnaire administration. Excluding those who
      described themselves as 'Other religious', 15.9% (n=418) described themselves as
      having no religious affiliation, 36.3% (n=957) were Christian, 25.8% (n=679) were
      Muslim and 22.1% were Hindu (n=582). The religious affiliation varied within and
      across different ethnic groups. METHOD: Self-administered questionnaire completed
      under 'exam' conditions, either in tutor groups or a school hall. The 30-minute
      questionnaires were distributed and collected by a team of ethnically and
      religiously diverse fieldworkers. RESULTS: Religious students, as opposed to
      those reporting no religious affiliation, generally reported poorer sexual health
      knowledge, and were more conservative in their attitudes to sex. Among males and
      females, those with no religious affiliation and Christian students reported the
      highest prevalence of sexual intercourse by some margin (around 20 percentage
      points) over the Hindus and Muslims. Christian males most frequently reported
      sexual intercourse at 49.7%, and Muslim females the least at 9.0%. Among those
      reporting sexual intercourse, risk behaviours among all religious and non
      religious students were evident. Over one-third of Muslim females who had sexual
      intercourse did not use contraception on their first occasion compared to 10% of
      those with no religious affiliation, 12% of Christians and 20% of Hindus.
      Christian and Muslim females reported the highest prevalence of ever not using
      contraception at 55%, and non-use of contraception with two or more sexual
      intercourse partners at 14%. CONCLUSION: The findings demonstrate diverse sexual
      health knowledge, sexual attitudes and sexual behaviours among young people with
      different religious affiliations. These variations demonstrate the importance of
      tailoring health education and promotion interventions to meet the specific needs
      of young people from a variety of different religions. The challenge ahead is to
      find ways to work with these young people to broach such sensitive issues.

PMID- 18066739
TI  - Seeking health care: Marshallese migrants in Hawai'i.
AB  - OBJECTIVE: The number of Marshallese migrants has dramatically increased in the
      US and its territories since the 1986 Compact of Free Association agreement.
      Their poor health status and patterns of untimely care are considered a great
      public concern in the host society. This paper examines the health care patterns
      of Marshallese migrants in Hawai'i and how their specific characteristics and
      circumstances affect their behaviors when seeking health care services. DESIGN:
      In-depth interviews were conducted with Marshallese migrants, key informants in
      the Marshallese community, and health and social service providers in the local
      community. RESULTS: This study reveals three important patterns of health care
      seeking behavior among Marshallese migrants. First, Marshallese migrants do not
      seek health care until they perceive a health crisis, usually indicated by pain.
      This cultural notion of 'present crisis-oriented health care' governs overall
      health care behaviors of Marshallese migrants. Second, Marshallese migrants are
      highly reliant on parochial networks for health care, given the strong mutual
      trust and the value assigned to interdependency within their culture. Despite
      many benefits of these networks, heavy dependence on them results in failure to
      obtain timely care when network resources become inaccessible or unavailable.
      Last, Marshallese migrants in Hawai'i do not rely on traditional health care
      practices as much as on the allopathic health care system. Their health care
      depends heavily on curative and tertiary care and health care assistance in the
      public sector. CONCLUSION: Health care seeking behaviors of migrants are shaped
      by cultural definition of health and health care and macro-social factors such as
      characteristics of the co-ethnic community and social networks, the health care
      system, and health policies, in addition to individual's socioeconomic status.
      These findings have important implications for community health care practices
      and policies.

PMID- 18066742
TI  - Molecular imaging by cardiovascular MR.
AB  - Do molecularly-targeted contrast agents have what it takes to usher in a paradigm
      shift as to how we will image cardiovascular disease in the near future?
      Moreover, are non-invasive vulnerable plaque detection and preemptive treatments
      with these novel nanoparticulate agents within reach for clinical applications?
      In this article, we attempt to make a compelling case for how the advent of
      molecularly-targeted nanoparticle technology may change the way we detect
      atherosclerotic lesions, determine their clinical significance and even provide
      non-invasive treatments. Focusing on imaging with cardiovascular MR, an overview
      of the latest developments in this rapidly evolving field of so-called
      "intelligent" contrast agents that are able to interrogate the vascular wall and
      various complementary advanced imaging technologies are presented.

PMID- 18066743
TI  - Improved quantitative assessment of left ventricular volumes using TGrE approach
      after application of extracellular contrast agent at 3 Tesla.
AB  - PURPOSE: To prospectively determine whether the use of an extracellular contrast
      agent could improve the image quality of TGrE sequence for evaluation of left
      ventricular (LV) volumes and function, using a 3.0 T cardiovascular magnetic
      resonance (CMR) system. METHODS: Fifteen consecutive patients underwent CMR
      imaging at 3.0 T. In each patient, 3 long axis views and multiple short axis
      slices with complete coverage of the left ventricle were performed using turbo
      gradient echo (TGrE) sequence before and after application of contrast agent 0.15
      mmol/kg gadopentetate dimeglumine. LV volumes and ejection fractions were
      calculated using Simpson's rule and Area-Length-Method. For comparison of native
      and postcontrast TGrE, image quality, blood-to-myocardium contrast, and cardiac
      function parameters were assessed. RESULTS: Application of contrast agent
      improves the image quality and blood-to-myocardium contrast in long-axis views.
      In short axis views, however, administration of contrast agent decrease the image
      quality and blood-to-myocardium contrast. After application of contrast agent in
      long axis scans, end-diastolic and end-systolic volumes were significantly larger
      (+ 12.9 mL [9%], p < 0.02; + 16.9 mL [17%], p < 0.004 respectively), and LV
      ejection fraction borderline lower (-4.1% [7%], p = 0.08). In short axis scans,
      however, end-diastolic and end-systolic volumes were significantly smaller (-14.8
      mL [13%], p < 0.001; -17.6 mL [21%], p < 0.004 respectively), and LV ejection
      fraction borderline higher (3% [6%], p = 0.052). CONCLUSION: The use of an
      extracellular contrast agent improves the image quality for the assessment of LV
      volumes at 3.0 Tesla for TGrE sequence in long axis but not in short axis views.

PMID- 18066744
TI  - Magnetic resonance evaluation of the associations of thoracic and abdominal
      aortic plaques with the presence and extent of coronary artery stenosis.
AB  - The association between coronary artery disease (CAD) and thoracic aortic plaques
      has often been reported using transesophageal echocardiography. However, studies
      showing the association between CAD and abdominal aortic plaques are scarce. CMR
      can visualize plaques in both the thoracic and abdominal aortas. Using CMR, we
      investigated the associations of thoracic and abdominal aortic plaques with the
      presence and extent of coronary artery stenosis in 146 patients undergoing
      coronary angiography, of whom 108 had CAD. The prevalence of thoracic and
      abdominal aortic plaques was higher in patients with CAD than in those without
      CAD (73% and 94% vs. 32% and 79%, p < 0.025). Stepwise increases in the
      prevalence and extents of both thoracic and abdominal plaques were found
      depending on the number of stenotic coronary vessels. Plaque extent in the
      thoracic aorta correlated with the numbers of > 50% and > 25% stenotic coronary
      segments (rs = 0.30 and 0.41). Plaque extent in the abdominal aorta also
      correlated with the numbers of > 50% and > 25% stenotic segments (rs = 0.40 and
      0.44). Notably, the total plaque extent in the aortas correlated best with the
      numbers of > 50% and > 25% stenotic coronary segments (rs = 0.41 and 0.49, p <
      0.001), and this factor was found to be the best predictor for the presence of
      CAD by the receiver-operating-characteristics curve analysis. Thus, the total
      plaque extent in the aortas was found to be more closely associated with the
      presence and extent of coronary stenosis than the thoracic or abdominal aortic
      plaque extent.

PMID- 18066745
TI  - Interobserver variability in assessing segmental function can be reduced by
      combining visual analysis of CMR cine sequences with corresponding parametric
      images of myocardial contraction.
AB  - OBJECTIVE: To evaluate if color-coded parametric images could help subjective
      visual analysis and improve interobserver agreement in the evaluation of
      segmental contraction (SC) in CMR. BACKGROUND: Routine evaluation of SC in CMR
      remains mostly based on visual analysis of cine loops and subsequent
      interobserver variability remains a potential drawback. MATERIALS AND METHODS:
      Three short axis cine loops were obtained in 33 subjects (18 myocardial
      infarction, 15 control), and 528 segments were analyzed. From each cine loop a
      single static parametric image resuming wall motion information was generated
      using Factor Analysis of Medical Image Sequences. Three readers (R1, R2, R3)
      scored left ventricular SC in 4 classes in 2 steps: visual assessment of cine
      loops alone and by combining cine loops with the corresponding parametric image.
      Reference segmental scores were obtained by consensus. Global contraction indexes
      were calculated in each step of the analysis. RESULTS: When parametric images
      were combined with cine loop assessment, interobserver agreement was enhanced for
      paired readers: R1-R2: kappa = 0.66 (combined analysis) vs. kappa = 0.60 (cine
      alone); R2-R3: kappa = 0.67 vs. kappa = 0.65; R3-R1: kappa = 0.71 vs. kappa =
      0.67 and absolute agreement with consensus was higher for the 3 readers: R1: 91%
      vs. 85%; R2: 87% vs. 83% and R3: 94% vs. 89%. When considering global wall motion
      indexes, interobserver agreement was also enhanced: R1 vs. R2 : r = 0.91 vs.
      0.85; R2 vs. R3: 0.95 vs. 0.91; R3 vs R1: 0.98 vs. 0.91. CONCLUSION: Adding a
      color-coded static parametric image to routine subjective visual assessment of SC
      reduces interobserver variability.

PMID- 18066746
TI  - Cardiac hemangioma: features on cardiovascular magnetic resonance.
AB  - We present a case of cardiac capillary hemangioma in a patient who presented with
      a history of recurrent episodes of syncope. Cardiovascular magnetic resonance
      played an important role in the diagnosis of cardiac hemangioma in our patient.

PMID- 18066747
TI  - Tissue cardiovascular magnetic resonance demonstrates regional diastolic
      dysfunction in remote tissue early after inferior myocardial infarction.
AB  - PURPOSE: To investigate regional diastolic and systolic function using tissue
      cardiovascular magnetic resonance (CMR), early after transmural myocardial
      infarction of the inferior wall due to single proximal right coronary artery
      disease. MATERIALS AND METHODS: Velocity encoded CMR was used to measure early
      diastolic transmitral flow velocity (E), and regional, longitudinal, myocardial
      systolic (Sa) and early diastolic (Ea) velocities (tissue CMR) in 15 patients
      with a recent transmural inferior myocardial infarction and in 15 age and LV-mass
      index matched control subjects. An unpaired two-tailed t test was used to assess
      significance of continuous variables. RESULTS: Global systolic (ejection fraction
      46 +/- 7% versus 57 +/- 4%, p = 0.000052) and global diastolic LV function
      (average Ea of infarcted or inferior, remote or anterior, adjacent or septal and
      lateral myocardium 6.8 +/- 1.7 cm/s versus 10.4 +/- 1.5 cm/s, p = 0.0000012) were
      impaired in patients as compared to controls. Regional systolic and diastolic LV
      velocities were impaired in infarcted and adjacent tissue in patients. However,
      in remote or anterior tissue, systolic velocities were preserved (Sa 6.6 +/- 2.0
      cm/s versus 6.8 +/- 1.4 cm/s, p = 0.70), but diastolic velocities were impaired
      in patients as compared to controls (Ea 7.2 +/- 2.3 cm/s versus 10.2 +/- 2.5
      cm/s, p = 0.0026). CONCLUSIONS: Regional diastolic velocities early after
      inferior myocardial infarction are impaired in the infarcted, adjacent and remote
      tissue, but regional systolic velocities are preserved in remote tissue.

PMID- 18066748
TI  - Improved cardiac tagging resolution at ultra-high magnetic field elucidates
      transmural differences in principal strain in the mouse heart and reduced stretch
      in dilated cardiomyopathy.
AB  - Cardiac tagging resolution for regional principal strains E1 and E2 has been a
      limiting factor for the study of dilated mouse hearts, in which the left
      ventricle (LV) wall thickness can drop to below 1 mm. Therefore, high resolution
      tagging was performed at 14.1 T to enable transmural principal strain
      measurements across the LV wall of normal mouse hearts and average principal
      strains in thinned LV walls of a transgenic mouse (PKCepsilon TG) that develops
      dilated LV. A modified DANTE tagging and fast gradient imaging method produced a
      tagging grid dimension of 0.33 x 0.33 mm and line thickness under 0.1 mm. In
      normal mice, average E1 strain in the epicardium was significantly higher than
      the endocardial E1 (epi = 0.22 +/- 0.10; endo = 0.13 +/- 0.07, p < 0.05), while
      magnitude of average endocardial E2 was greater than in the epicardium (endo = 
      0.12 +/- 0.03, epi = -0.08 +/- 0.03; p < 0.001). E1 strain averaged over four
      segments was reduced in dilated hearts compared to controls (PKCepsilon TG = 0.14
      +/- 0.02; control = 0.18 +/- 0.02, p < 0.01), with specific reductions in septal
      (33%) and lateral (31%, p < 0.01) segments. E2 strain was similar between dilated
      and control hearts at -0.11 +/- 0.01. Thus, improved tagging resolution
      demonstrates that stretch (E1), but not compression strains (E2), are reduced as
      a result of significant LV wall thinning in a mouse model of dilated
      cardiomyopathy.

PMID- 18066749
TI  - Altered myocardial motion pattern in Fabry patients assessed with CMR-tagging.
AB  - Progressive left ventricular hypertrophy is the hallmark of cardiac
      manifestations in patients with Fabry disease. Cardiovascular magnetic resonance
      with tissue tagging allows detailed assessment of the cardiac motion pattern. The
      aim was to test the hypothesis that not only Fabry patients with severe left
      ventricular hypertrophy exhibit changes in myocardial motion, but also Fabry
      patients with normal left ventricular mass. Magnetic resonance tagging using
      slice following complementary spatial modulation of magnetization (CSPAMM)
      combined with harmonic phase analysis (HARP) was applied to measure left
      ventricular shortening and contraction. Additionally, left ventricular rotation
      and global left ventricular torsion were examined. Twenty-nine Fabry patients
      grouped in patients with (n = 13) and without (n = 16) left ventricular
      hypertrophy were compared with 29 age and sex matched healthy volunteers. Long
      axis shortening and circumferential contraction showed reduced peak values with
      increasing left ventricular mass and were significantly reduced in Fabry patients
      with left ventricular hypertrophy (p < 0.001 and p < 0.05, respectively).
      Torsional deformation and apical rotation were increased both in Fabry patients
      with left ventricular hypertrophy as well as in patients with normal left
      ventricular mass (p < 0.001 for torsion) compared with controls. Applying the
      magnetic resonance tagging acquisition and analysis methods, myocardial motion
      abnormalities could not only be measured in Fabry patients with left ventricular
      hypertrophy but also in patients without macroscopic cardiac involvement.

PMID- 18066750
TI  - A simplified continuity equation approach to the quantification of stenotic
      bicuspid aortic valves using velocity-encoded cardiovascular magnetic resonance.
AB  - OBJECTIVE: We aimed to compare velocity-encoded cine cardiac magnetic resonance
      (CMR) with an established echocardiographic method for noninvasive measurement of
      aortic valve area (AVA) using the continuity equation. METHODS AND RESULTS:
      Twenty consecutive young adults with stenotic bicuspid aortic valves were
      examined with CMR and transthoracic echocardiography (TTE). CMR AVA was
      calculated by the continuity equation, dividing stroke volume by the aortic
      velocity-time integral (VTIAorta), the stroke volume measured both by ventricular
      volume analysis and by phase contrast velocity mapping at 4 levels (1 subvalvar
      and 3 supravalvar). Stroke volumes measured at all levels correlated well with
      those from volumetric analysis. The CMR AVAs calculated using volumetric analysis
      and VTIAorta from jet velocity mapping correlated and agreed well with TTE AVA
      measurements (R2 = 0.83). When CMR AVA was calculated more rapidly using volume
      flow and VTIAorta both measured from the same trans-jet velocity acquisition, R2
      was 0.74, with a bias and limits of agreement of 0.02 (-0.44, 0.47) cm2.
      CONCLUSIONS: Continuity equation calculation of the AVA using CMR velocity
      mapping, with or without ventricular volumetric measurement, correlated and
      agreed well with the comparable and widely accepted TTE approach.

PMID- 18066751
TI  - Mid-myocardial fibrosis by cardiac magnetic resonance in patients with lamin A/C
      cardiomyopathy: possible substrate for diastolic dysfunction.
AB  - AIMS: We sought to identify patterns of myocardial fibrosis in vivo in patients
      with lamin cardiomyopathy, and to determine its functional significance. METHODS
      AND RESULTS: Eleven patients sharing the identical mutation in LMNA without
      contraindication to magnetic resonance were identified from a 1016-member
      pedigree. Eight autopsy hearts from deceased relatives were reviewed. Patients
      and age-matched controls underwent cardiac magnetic resonance that included
      measures of cardiac function and late gadolinium enhancement (LGE). LGE-CMR
      identified midmyocardial fibrosis of the basal interventricular septum in 5 of 11
      LMNA patients that was identical to that seen in 6 autopsy specimens of related
      genotype-positive family members; this was not present in any of 11 controls. LGE
      CMR was positive in the 5 oldest patients in the cohort, age 46 +/- 6 years
      compared to 24 +/- 10 years for LGE-negative subjects (p = 0.003). Systolic
      function was abnormal in 2 subjects, both with myocardial fibrosis. LGE
      positivity distinguished patients with diastolic dysfunction by mitral inflow
      velocities from those with normal diastolic function; these patients also had
      significant left atrial enlargement compared to controls (p < 0.05). CONCLUSIONS:
      LGE-CMR can identify myocardial fibrosis under genetic control in vivo in
      patients with heritable cardiomyopathy similar in distribution to that observed
      at autopsy. Mid-myocardial fibrosis may form the substrate for diastolic
      dysfunction in these patients.

PMID- 18066752
TI  - High resolution magnetic resonance imaging of excised atherosclerotic carotid
      tissue: the effects of specimen temperature on image contrast.
AB  - Previous Magnetic Resonance (MR) studies of carotid endarterectomy (CEA)
      specimens have been directed at interpreting image contrast to determine plaque
      composition and stability. Such studies may give misleading results since it is
      believed that the acquired MR data is affected by the conditions used to store
      the excised tissue. This has been investigated in a high-resolution imaging study
      of the changes in contrast occurring with a change in specimen temperature. MR
      images were acquired from 20 CEA specimens. The initial MR examination was made
      within four hours of excision in tissue maintained and imaged at body
      temperature. Specimens were subsequently cooled and then re-examined at different
      times. The MR data was interpreted by comparison with histology obtained from
      equivalent sections. With the exception of signals arising from blood, changes in
      MR image contrast occurring in the 24-hour period after the CEA were relatively
      slight. Plaque lipid T2-weighted image intensity was initially relatively
      hyperintense in some samples and decreased with time on cooling reflecting a
      decrease in the lipid transverse (T2) relaxation time. High-resolution imaging
      allowed a detailed description of plaque calcification and showed that clot
      retraction was probably responsible for the marked change in the distribution of
      signals assigned to intraluminal blood. The use of high-resolution MR imaging to
      examine freshly excised specimens at body temperature showed previously
      unreported image features. This is important in the design of in vivo MR studies
      directed at assessing plaque stability by identifying the composition of the
      atheromatous tissue.

PMID- 18066753
TI  - The influence of left ventricular size and global function on regional myocardial
      contraction and relaxation in an adult population free of cardiovascular disease:
      a tagged CMR study of the MESA cohort.
AB  - The purpose of this study is to evaluate the relationship between LV structure
      and function with regional myocardial function in participants of the Multi
      Ethnic Study of Atherosclerosis, which is a prospective study including 4 ethnic
      groups free from clinical cardiovascular disease. Peak systolic strain (Ecc) and
      regional strain rates (SRS and SRE) were calculated by harmonic phase from tagged
      CMR of 1100 participants. The relationships of ejection fraction (EF), end
      systolic volume (ESV) and end-diastolic volume (EDV) with Ecc and strain rate
      were studied before and after adjustment for cardiovascular risk factors. Direct
      linear relationships between EF and regional systolic and diastolic functions
      (Ecc, SRS and SRE) were present in almost all of the regions (p < 0.05, i.e.,
      greater EF, greater Ecc, SRS and SRE). LVESV demonstrated a negative relationship
      with Ecc and SRS (i.e., greater ESV, lower systolic function, indexed by Ecc and
      SRS) in all regions (p < or = 0.05). LVEDV was inversely related to systolic
      function, indexed by SR(S) (p < 0.05) in all regions. In conclusion, LVEF is
      directly related to systolic myocardial function, indexed as the absolute
      magnitude of systolic strain and strain rate. In addition, left ventricular size,
      indexed as end-diastolic and end-systolic volumes are inversely related to
      absolute systolic myocardial strain rate (SRS). These results are crucial to the
      interpretation of strain alterations induced by left ventricular remodeling in
      early heart failure.

PMID- 18066754
TI  - Kinetics of C. elegans DcpS cap hydrolysis studied by fluorescence spectroscopy.
AB  - DcpS (scavenger decapping enzyme) from nematode C. elegans readily hydrolyzes
      both monomethyl- and trimethylguanosine cap analogues. The reaction was followed
      fluorimetrically. The marked increase of fluorescence intensity after the
      cleavage of pyrophosphate bond in dinucleotides was used to determine K(m) and
      V(max)values. Kinetic parameters were similar for both classes of substrates and
      only slightly dependent on pH. The hydrolysis was strongly inhibited by methylene
      cap analogues (m(7)Gp(CH(2))ppG and m(7)Gpp(CH(2))pG) and less potently by ARCA
      (m(7,3' O)GpppG).

PMID- 18066755
TI  - Synthesis of C8-modified 2''-deoxyadenosine with carcinogenic arylamines.
AB  - The synthesis of phosphoramidites of C8-modified 2'-deoxyadenosine with
      carcinogenic arylamines p-anisidine and 4-aminobiphenyl is described. Two
      different methods were studied related to the glycon and base protection groups.

PMID- 18066756
TI  - Polyaza crown ether as non-nucleosidic building blocks in DNA-conjugates.
AB  - The synthesis of amphiphilic polyaza crown ether monomers X (palmityl
      substituted), Y (cholesteryl-substituted) and Z (dipalmityl-subtituted) and their
      incorporation into oligonucleotides are described. Their effects on thermal
      duplex stability were investigated by UV melting curve analysis. Thermal
      denaturation experiments showed remarkable stabilization of dsDNA by polyaza
      crown ether monomers when incorporated in opposite positions. The series of
      polyaza crown ether monomers (X, Y, and Z) with different lipophilicity showed a
      trend of increased stability of the corresponding dsDNA with increasing
      lipophilicity of the polyaza crown ether monomer.

PMID- 18066757
TI  - Synthesis and biophysical characterization of G-rich oligonucleotides conjugated
      with sugar-phosphate tails.
AB  - A number of 5'-and 3'-glycoconjugates of the oligonucleotide (5')d(TGGGAG)(3')
      have been synthesized, exploiting fully automated, online phosphoramidite-based
      solid phase strategy, as potential anti-HIV-1 agents. The thermodynamic stability
      of the resulting quadruplexes has been investigated by thermal denaturation
      studies, via a detailed CD Q1 analysis.

PMID- 18066758
TI  - Synthesis and characterization of tetra-end linked oligonucleotides capable of
      forming monomolecular G-quadruplexes.
AB  - The chemical synthesis of two new G-rich Tetra-End-Linked
      oligodeoxyribonucleotides (TEL-ODNs) as well as (1)H-NMR and CD spectra of the
      corresponding monomolecular quadruplexes (IVa and IVb) has been reported. The new
      TEL-ODNs, characterized by the presence of short branches in the linker moiety,
      could be very useful for the achievement of monomolecular quadruplexes with
      predetermined strand orientation.

PMID- 18066759
TI  - Synthesis study of 2'-O-(2-methoxyethyl)-purine derivatives.
AB  - Alkylation of adenosine and 2-aminoadenosine was studied in dimethylsulfoxide
      with application of 1-methanesulfonyloxy-2-methoxyethane as an alkylating agent
      and t-BuOK, KOH and NaH as bases under mild heating. Using new reaction
      conditions, the improved synthesis of 2'-O-MOE-purine derivatives is described.

PMID- 18066760
TI  - Synthesis of L-2'-deoxypentofuranonucleoside derivatives of thymine from D
      glucose.
AB  - Convergent synthesis of L-2'-deoxypentofuranonucleoside derivatives of thymine
      was carried out from D-glucose via 6-O-toluoyl-3-deoxy-1,2-O-isopropylidene-beta
      L-lyxo-hexofuranose as a key intermediate.

PMID- 18066761
TI  - Novel CoA-polyamine conjugates for effective inhibition of spermine/spermidine-N1
      acetyltransferase.
AB  - New mimics of the transition state of spermine/spermidine-N(1)-acetyltransferase
      reaction were prepared starting from aminooxy analogues of spermidine or spermine
      and SH-CoA. The activity depended on the structure of polyamine fragment of the
      conjugate and best of the synthesized compounds were active at micromolar
      concentrations.

PMID- 18066762
TI  - Efficient synthesis of benzamide riboside, a potential anticancer agent.
AB  - An efficient five step synthesis of benzamide riboside (BR) amenable for a large
      scale synthesis has been developed. It allows for extensive pre-clinical studies
      of BR as a potential anticancer agent.

PMID- 18066763
TI  - Fission yeast telomeric DNA binding protein Pot1 has the ability to unfold
      tetraplex structure of telomeric DNA.
AB  - To understand the regulation mechanism of fission yeast telomeric DNA, we
      analyzed the structural properties of 4Gn: d(G(n)TTAC)(4) (n = 3, 4) and their
      interaction with the single-stranded telomeric DNA binding domain of telomere
      binding protein Pot1 (Pot1DBD). 4G4 adopted only an antiparallel tetraplex in
      spite of a mixture of parallel and antiparallel tetraplexes of 4G3. The
      antiparallel tetraplex of 4G4 became unfolded upon the interaction with Pot1DBD.
      Considering that the antiparallel tetraplex inhibits telomerase-mediated telomere
      elongation, we conclude that the ability of Pot1 to unfold the antiparallel
      tetraplex is required for telomerase-mediated telomere regulation.

PMID- 18066764
TI  - Dual-probe system using pyrenylmethyl-modified amino-LNA for mismatch detection.
AB  - A dual-probe containing pyrenylmethyl amino-LNA has been developed for sensitive
      mismatch detection. While hybridization with complementary DNA/RNA results in
      very strong excimer signals, exposure to singly mismatched DNA/RNA targets
      results in significantly decreased excimer emission.

PMID- 18066765
TI  - Development of artificial restriction DNA cutter composed of Ce(Iv)/EDTA and PNA.
AB  - An artificial restriction enzyme, which we developed recently by combining
      Ce(IV)/EDTA and peptide nucleic acids, was used for PCR-free construction of a
      fusion protein. The fusion protein was successfully expressed in mammalian cells.
      This artificial DNA cutter can be also applied to site-selective scission of huge
      DNAs. Promising features of this novel tool were concretely evidenced.

PMID- 18066766
TI  - Sulfur containing acyclovir derivatives: synthesis, cytotoxic activity, and cell
      phenotype studies.
AB  - New 2-amino-6-oxo-8-thioxo-9-substituted purine derivatives were prepared and
      assayed for the in vitro cytotoxic activity. Some products exhibited moderate
      activity on HT-1080 cells and rather high activity on MG-22A cells.

PMID- 18066767
TI  - A convenient solid-phase method for the synthesis of novel oligonucleotide-folate
      conjugates.
AB  - We describe the preparation of two batches of a polymer support for the
      incorporation of folic acid into oligonucleotides. The method permits the
      regioselective attachment of a target nucleic acid sequence through its 3'-end to
      either the alpha-or gamma-carboxyl group of L-glutamic acid, respectively. The
      supports have been tested in solid-phase synthesis of oligonucleotide-folate
      conjugates for cell delivery studies.

PMID- 18066768
TI  - Stepwise functionalization of ribonucleopeptides: optimization of the response of
      fluorescent ribonucleopeptide sensors for ATP.
AB  - A stable complex of a peptide and RNA, ribonucleopeptide (RNP), provides a new
      framework to construct a macromolecular receptor for small molecules. The RNP
      receptor functionalized by a fluorophore-labeled Rev peptide exerts an optical
      signal associated with the ligand binding events. Replacing the Rev peptide of
      the ATP-binding RNP with a fluorophore-modified Rev peptide affords a fluorescent
      ATP sensor.

PMID- 18066769
TI  - 2'-o-dimethylaminoethoxyuridine and 5-dimethylaminopropargyl deoxyuridine for at
      base pair recognition in triple helices.
AB  - The nucleoside analogues 2'-O-dimethylaminoethoxy uridine and 5
      dimethylaminopropargyl deoxyuridine have been synthesised and incorporated into
      oligonucleotides. Their triplex-stabilising properties have been determined in
      fluorescence melting experiments.

PMID- 18066770
TI  - Oligonucleotide synthesis using ionic liquids as soluble supports.
AB  - The continuing evolution of the methodology for the solution-phase synthesis of
      oligonucleotides using soluble ionic tags as handles for easy purification is
      described. This methodology may provide a more cost efficient route for the large
      scale synthesis of oligonucleotides.

PMID- 18066771
TI  - Optical tweezers as a probe for oligodeoxyribonucleotide structuration.
AB  - The aim of this work is to investigate if the optical tweezers (OT) are suitable
      as a diagnostic tool for monitoring the oligodeoxyribonucleotide (ODN) structural
      behavior in solution. Preliminary experiments, performed on the quadruplex formed
      by the ODN sequence TGGGGT, showed that the OT can be used as a probe for ODN
      structuration by monitoring the medium viscosity changes associated with ODN
      folding-unfolding processes.

PMID- 18066772
TI  - Assignment of the absolute configuration of P-chiral 5' mRNA cap analogues
      containing phosphorothioate moiety.
AB  - Enzymatic cleavage of the P-chiral diastereoisomers of the 5' mRNA cap analogue
      bearing phosphorothioate moiety in alfa position of 5',5'-triphosphate bridge
      (m(7)Gppp(S)G D1 and D2) was performed by human Decapping Scavenger (DcpS)
      enzyme. Analysis of the degradation products allowed to estimate the absolute
      configuration at the asymmetric phosphorus atoms in examined compounds via
      correlation with the R(P) and S(P) diastereoisomers of guanosine 5'-O-(1
      thiodiphosphate) (GDPalphaS).

PMID- 18066773
TI  - dabPNA: design, synthesis, and DNA binding studies.
AB  - In continuing our research efforts for developing new oligodeoxynucleotide (ODN)
      like drugs and diagnostics, we designed diaminobutyric peptide nucleic acids
      (dabPNAs), nucleopeptides characterized by a diaminobutyric-based building block
      that is an isomer of the aminoethylglycyl PNA (aegPNA) unit and the acyclic
      modification of the aminoprolyl PNA (ampPNA) monomer. In this work we present the
      solid phase synthesis of a dabPNA oligomer and of two aegPNAs containing a single
      dabPNA unit. A study relative to their binding ability towards DNA is also
      reported even in comparison with the well known aegPNAs.

PMID- 18066774
TI  - 2',3'-isopropylidene group, a molecular scaffold to study the activity of
      adenosine and adenylate deaminase on adenosine analogues modified in the ribose
      moiety.
AB  - 2 ',3 '-Isopropylidene group can be used as a molecular scaffold for the
      introduction of modifications at 5 ' and 1 ' positions of adenosine and these
      modified nucleosides are used to evaluate the biocatalytic activity of adenosine
      and adenylate deaminase.

PMID- 18066775
TI  - Synthesis of 3H and 13C labeled mRNA cap dinucleotides--useful tools for NMR,
      biochemical, and biological studies.
AB  - For deeper understanding the roles of the mRNA cap structure in cellular
      processes isotopically labeled dinucleotide cap analogues have been synthesized
      as tools for NMR and in vivo studies. Tritium or carbon C-13 labeled methyl
      iodide was used as a source of the isotope material. In order to minimize the
      number of steps during the radioisotopic synthesis the methylation with tritium
      labeled methyl iodide was performed with Gp(3)G as a substrate. The C-13 isotope
      was introduced into the cap dinucleotide by methylation of GDP with C-13 Methyl
      iodide, followed by coupling the product with guanosine 5'-phosphorimidazolide in
      DMF with zinc chloride as a catalyst.

PMID- 18066776
TI  - Synthesis of a new ribose modified analogue of cyclic inosine diphosphate ribose.
AB  - A new analogue of cyclic inosine diphosphate ribose (cIDPR), in which the N-1 and
      N-9 ribosyl moieties were substituted by an alkyl moiety and an hydroxy-alkyl
      chain, has been synthesized and characterized.

PMID- 18066777
TI  - New developments of the "lock-in" modified cycloSal-d4TMPs.
AB  - New developments of the "lock-in" modified cycloSal-d4TMP are reported. Novel
      prodrugs with variations in the linker chain were introduced. The synthesis,
      hydrolysis properties in different media (PBS, CEM/0- and liver extracts) and the
      antiviral activities against HIV are shown.

PMID- 18066778
TI  - Solid-supported synthesis of 5'-mRNA CAP-4 from Trypanosomatids.
AB  - The unique structure of 5' mRNA cap from Trypanosomatids is the most modified cap
      found in nature. Here we present the synthesis of cap-4
      (m(7)Gpppm(3)(6,6,2')Apm(2')Apm(2')Cpm(2)(3,2')Up) on a disulfide-tethered solid
      support. This approach allows obtaining cap-4 more efficiently then previously
      described. Moreover such modified resin could be a useful tool for affinity
      purification of Leishmania proteins interacting with cap-4. For the final step of
      synthesis, namely coupling of phosphorylated tetranucleotide with activated 7
      methylguanosine 5'-diphosphate two systems were compared. Surprisingly, the
      coupling in water with Mn(2+) as a catalyst, gave better results than usually
      more effective coupling in DMF with ZnCl(2).

PMID- 18066779
TI  - A pyrimidopyrimidoindole nucleoside (dC PPI): photophysical properties and
      thermal stability of the modified DNA duplexes.
AB  - A new fluorescent deoxycytidine analog, 10-(2-deoxy-beta -D-ribofuranosyl)
      pyrimido[4',5' :4,5]-pyrimido[1,6-a]indole-6,9(7H)-dione (dC(PPI)) was
      synthesized. Its fluorescent properties were studied in detail. It was found that
      this fluorescent nucleoside dC(PPI) could be used as a fluorescent label for DNA
      probes with minimal disturbance of their overall structure.

PMID- 18066780
TI  - Synthesis of Leishmania cap-4 intermediates, cap-2 and cap-3.
AB  - Synthesis of Leishmania mRNA 5'-cap analogs, m(7)Gpppm(2)(6)AmpAm (cap-2), and
      m(7)Gpppm(2)(6)AmpAmpCm (cap-3) is reported. Binding affinities of those cap
      analogs for LeishIF4E proteins were determined using fluorescence spectroscopy.
      Cap-3 showed similar affinity to LeishIF4Es compared to the mature
      trypanosomatids cap structure (cap-4).

PMID- 18066781
TI  - Affinity of dinucleotide cap analogues for human decapping scavenger (hDcpS).
AB  - Eukaryotic cells utilize scavenger decapping enzymes to degrade cap structure
      following 3'-5' mRNA decay. Human DcpS recently has been described as a highly
      specific hydrolase (a member of the HIT family) that catalyses the cleavage of
      m(7)GpppG and short capped oligoribonucleotides. We have demonstrated here that
      cap-1 (m(7)GpppGm) is a preferred substrate among several investigated
      dinucleotide cap analogues m(7)Gp(n)N (n = 3-5, N is a purine or pyrimidine base)
      and m(7)GMP is always one of the reaction product. Cap analogues containing
      pyrimidine base instead of guanine or diphosphate chain are resistant to
      hydrolysis catalyzed by human scavenger. Contrary to the other enzymes of HIT
      family, hDcpS activity is not stimulated by Mg(2+).

PMID- 18066782
TI  - Evaluation of different chemical strategies for conjugation of oligonucleotides
      to peptides.
AB  - We developed novel assays for high-throughput detection of one or many kinases or
      proteases. The assays use hundreds of different peptide substrates, each
      covalently linked to an oligonucleotide tag. After incubation with sample, the
      pool of substrates is hybridized to a microarray containing oligonucleotides
      complementary to the tag sequences. We screened several specific chemistries for
      the conjugation based on the following criteria: easy derivatization of
      oligonucleotides and peptides; high efficiency of the conjugation reaction; good
      stability of the conjugates; and satisfactory conjugate performance in our
      assays. We have validated selected method during the successful generation of
      thousands oligonucleotide-peptide conjugates.

PMID- 18066783
TI  - Synthesis and incorporation of a simple acyclic furan containing phosphoramidite.
AB  - A novel furan containing phosphoramidite was synthesized and incorporated into
      model oligonucleotides. This glycol nucleic acid based building block contains a
      furan unit substituting the natural base, and can be used for post synthetic
      oligonucleotide modifications by orthogonal chemistries such as Schiff base
      formation after in situ oxidation or Diels-Alder cycloadditions.

PMID- 18066784
TI  - CG base pair recognition within DNA triple helices using N-methyl-3H-pyrrolo[2,3
      d]pyrimidin-2(7H)-one nucleoside analogues.
AB  - Triplex-mediated recognition of Py.Pu base pairs in DNA is a greater challenge
      than for Pu.Py base pairs as fewer hydrogen bonds are presented for binding in
      the major groove. Initial studies on m-aminophenyl-modified analogues of the
      bicyclic nucleoside N-methyl-3H-pyrrolo[2,3-d]pyrimidin-2(7 H)-one suggest that
      selective recognition of the CG base pair is possible.

PMID- 18066785
TI  - Looking for new pyrimidine acyclic nucleotide analogues designed for
      phosphorylation by human UMP-CMP kinase.
AB  - Human UMP-CMP kinase is involved in the phosphorylation of nucleic acid
      precursors and also in the activation of antiviral analogues including cidofovir,
      an acyclic phosphonate compound that mimicks dCMP and shows a broad antiviral
      spectrum. The binding of ligands to the enzyme was here investigated using a
      fluorescent probe and a competitive titration assay. At the acceptor site, the
      enzyme was found to accommodate any base, purine and pyrimidine, including
      thymidine. A method for screening analogues based on their affinity for the UMP
      binding site was developed. The affinities of uracil vinylphosphonate derivatives
      modified in the 5 position were found similar to (d)UMP and (d)CMP and improved
      when compared to cidofovir.

PMID- 18066786
TI  - Enantio-selectivity of human nucleoside monophosphate kinases.
AB  - Over recent years, there has been a renewed interest in the development of L
      nucleosides as safe and efficacious drugs for the treatment of viral infections.
      Biological activity of these compounds requires phosphorylation to their
      triphosphate form, involving nucleoside monophosphate kinases in the second step.
      In order to characterize the activation pathway of L-nucleosides of the
      pyrimidine series, we studied the enantio-selectivity of human uridylate
      cytidylate and thymidylate kinases. The results showed that these enzymes are
      only weakly enantio-selective and are thus probably involved in the activation of
      L-nucleosides in vivo. An activation pathway for telbivudine (L-dT) was therefore
      proposed.

PMID- 18066787
TI  - Synthesis of pyrene labeled RNA for fluorescence measurements.
AB  - The fluorophores 1-ethynylpyrene and 1-(p-ethynyl-phenylethynyl)-pyrene were
      attached to RNA through a Sonogashira cross-coupling with 5-iodocytidine either
      in solution through phosphoamidite synthesis or via on-column conjugation during
      solid-phase oligonucleotide synthesis. Six probes with the sequence 5'-CUU UUC
      UUU CUU-3' were derivatized with both fluorophores, whereby the position of the
      modified cytidine was varied. Fluorescence measurements showed sensitivity of the
      pyrene group to its environment in the single strands and corresponding duplexes.

PMID- 18066788
TI  - Synthesis of 9-(2,3-dideoxy-2,3-difluoro-beta-D-arabinofuranosyl)adenine.
AB  - Convergent synthesis of 9-(2,3-dideoxy-2,3-difluoro-beta-D
      arabinofuranosyl)adenine is described starting from methyl 5-O-benzyl-2-deoxy-2
      fluoro-alpha-D-arabinofuranoside.

PMID- 18066789
TI  - Alkyne-azide click chemistry mediated carbanucleosides synthesis.
AB  - Hitherto unknown 1,4-disubstituted-[1,2,3]-triazolo-4',4'-dihydroxymethyl-3'
      deoxy carbanucleosides were synthesized based on a "click approach." Various
      alkynes were introduced on a key azido intermediate by the "click" 1,3-dipolar
      Huisgen cycloaddition. Their antiviral activities and cellular toxicities were
      evaluated on vaccinia virus. None of the synthesized compounds exhibited a
      significant antiviral activity.

PMID- 18066790
TI  - Supported synthesis and functionnalization of 2''-deoxyuridine by Suzuki-Miyaura
      cross-coupling.
AB  - The synthesis and modification of 2'-deoxyuridine has been realized under Suzuki
      Miyaura palladium-catalyzed cross-coupling conditions. Using Pd(PPh(3))(4) and
      Na(2)CO(3), 5-iodo-2'-deoxyuridine bound to solid support is coupled with various
      boronic acids to give 5-(hetero)aryl-2'-deoxyuridine. Pd(PPh(3))(4) palladium
      catalyzed was found to be superior to Pd(OAc)(2) and (NHC)Pd(allyl)Cl for Suzuki
      Miyaura palladium-catalyzed reactions.

PMID- 18066792
TI  - Synthesis and biophysical studies of N2'-functionalized 2'-amino-alpha-L-LNA.
AB  - A synthetic route towards a selected set of N-acylated and N-alkylated
      derivatives of 2'-amino-alpha-L-LNA phosphoramidite building blocks has been
      developed. Biophysical studies suggest that the 2-oxo-5-azabicyclo[2.2.1]heptane
      skeleton of 2'-amino-alpha-L-LNA allows precise positioning of intercalators in
      the core of nucleic acid duplexes.

PMID- 18066791
TI  - Cross-metathesis mediated synthesis of new acyclic nucleoside phosphonates.
AB  - With the commercial availability of well-defined ruthenium metathesis catalysts
      which combine high stability and broad functional group compatibility, olefin
      metathesis is now routinely integrated in various syntheses. We will report here
      the overwhelming power and scope of cross-metathesis in the area of new acyclic
      nucleoside phosphonates. Scope and limitations of this approach, and especially
      the E/Z stereocontrol, are discussed on selected examples from our drug discovery
      group.

PMID- 18066793
TI  - Pyrene-functionalized 2'-amino-alpha-L-LNA as potential diagnostic probes.
AB  - Oligodeoxyribonucleotides (ONs) containing two incorporations of 2'-N-(pyren-1
      yl)acetyl-2'-amino-alpha-L-LNA monomer Y are sensitive probes for detection of
      single nucleotide polymorphisms (SNP) in DNA. In addition, the ability of ONs
      containing pyrene-functionalized 2'-amino-alpha-L-LNA monomers (W-Z) to stabilize
      duplexes with an abasic site is demonstrated.

PMID- 18066794
TI  - Triplex-forming ability of modified oligonucleotides.
AB  - We present our studies on the ability of several different nucleotide analogs as
      triplex-forming oligonucleotides. The modifications tested include 4'-C
      hydroxymethyl, LNA, 2'-amino-LNA and N2'-functionalized 2'-amino-LNA. Triplexes
      containing monomers of N2'-glycyl-functionalized 2'-amino-LNA are particularly
      stable.

PMID- 18066795
TI  - N2'-functionalized 2'-amino-alpha-L-LNA adenine derivatives--efficient targeting
      of single stranded DNA.
AB  - The synthesis of two pyrene-functionalized 2'-amino-alpha-L-LNA adenine building
      blocks is outlined and initial results from thermal denaturation studies are
      presented.

PMID- 18066796
TI  - Toward a catalytic site in DNA: polyaza crown ether as non-nucleosidic building
      blocks in DNA conjugates.
AB  - A number of functionalized polyaza crown ether building blocks have been
      incorporated into DNA-conjugates as catalytic Cu(2+) binding sites. The effect of
      the DNA-conjugate catalyst on the stereochemical outcome of a Cu(2+)-catalyzed
      Diels-Alder reaction will be presented.

PMID- 18066797
TI  - Cu2+TerPy complexes as catalysts of the cleavage of the 5'-cap structure of mRNA.
AB  - Cu(2+)TerPy is a fairly good catalyst of the cleavage of dinucleoside
      triphosphates, but its efficiency is not sufficient for use in artificial RNA
      cleaving enzymes. The present work is aimed at improving the catalysis by
      Cu(2+)TerPy with additional catalysts. Electrophilic and general acid catalysis
      have been studied and bifunctional catalysts have been synthesized. The most
      efficient catalysis was achieved with a Cu(2+)TerPy-dimer.

PMID- 18066798
TI  - Survivin mRNA antagonists using locked nucleic acid, potential for molecular
      cancer therapy.
AB  - We have investigated the effects of different locked nucleic acid modified
      antisense mRNA antagonists against Survivin in a prostate cancer model. These
      mRNA antagonists were found to be potent inhibitors of Survivin expression at low
      nanomolar concentrations. Additionally there was a pronounced synergistic effect
      when combining the mRNA antagonists against Survivin with the chemotherapeutic
      Taxol. This effect was demonstrated at concentrations of antagonists far lower
      than any previously demonstrated, indicating the high potential of locked nucleic
      acid for therapeutic use. Further characterisations in vivo are ongoing.

PMID- 18066799
TI  - Synthesis of 1'-C-fluoromethyladenosine.
AB  - In search for new antiviral agents, we have been interested in 1'-C-fluoromethyl
      branched ribonucleosides. In this paper, we describe the synthesis of 1'-C
      fluoromethyladenosine via electrophilic fluorination of exo-glycal.

PMID- 18066800
TI  - Synthesis of nucleosides with additional nucleobases.
AB  - The syntheses of two nucleosides with additional nucleobases in the 2'-position
      are presented. The nucleosides have two- and one-carbon linkers to the additional
      nucleobase, respectively. The two nucleosides are synthesized from different
      strategies. The nucleoside with two carbons in the linker has been incorporated
      into oligonucleotides and showed stabilization of a tree-way junction.

PMID- 18066801
TI  - Synthesis and stability studies of 2',3',5'-tri-O-acetyl-2-amino(-N6-cyclopentyl)
      1-deazaadenosines.
AB  - In this article, we report on the synthesis of 2',3',5'-tri-O-acetyl-2-amino-1
      deazaadenosine and of 2',3',5'-tri-O-acetyl-2-amino-N(6)-cyclopentyl-1
      deazaadenosine, which are very versatile intermediates for the preparation of 2
      substituted 1-deazaadenosine derivatives. The two synthesized compounds showed to
      be quite unstable, with the N(6)-substituted derivatives being less stable than
      the N(6)-unsubstituted counterpart, according to the calculated HOMO-LUMO energy
      gap. Stability studies were performed through HPLC-MS analysis.

PMID- 18066802
TI  - Synthesis and biological activity of trisubstituted adenines as A 2A adenosine
      receptor antagonists.
AB  - The discovery of new drugs for the treatment of neurodegenerative disorders, such
      as Parkinson's disease, has become an attractive field of research. Due to the
      regulation of D(2) receptor activity by A(2A) adenosine receptor, potent and
      selective ligands of A(2A) subtype could be useful tools to study
      neurodegenerative disorders. A series of 2,8-disubstituted-9-ethyladenine
      derivatives was synthesized and tested in binding affinity assay at human
      adenosine receptors. New compounds showed good affinity and selectivity at A(2A)
      receptor versus the other subtypes. The introduction of a bromine atom in 8
      position increased the affinity of these compounds, leading to ligands with K(i)
      in the nanomolar range.

PMID- 18066803
TI  - Bent oligonucleotide duplexes as HMGB1 inhibitors: a comparative study.
AB  - In this work we explore the ability of a chimeric LNA/DNA bent duplex, in which
      the kink is induced by 2 unpaired adenines in the middle of one strand, to bind
      HMGB1, a protein involved in many inflammatory processes. The LNA/DNA duplex was
      compared with the corresponding full DNA and PNA/DNA chimera duplexes from a
      thermodynamic and spectroscopic point of view.

PMID- 18066804
TI  - Solid-phase synthesis of modified RNAs containing amide-linked
      oligoribonucleosides at their 3'-end and their application to siRNA.
AB  - siRNAs against luciferase mRNA were modified with amide-linked
      oligoribonucleosides (amide-linked RNA) at their 3 '-overhangs. Tm values of the
      modified siRNAs increased compared with that of the unmodified siRNA. These
      results indicate that the modified overhangs increase the thermodynamic stability
      of the siRNAs. The modified overhangs improved stability of siRNAs against
      degradation by nuclease S1 and 50% mouse plasma. Furthermore the modified siRNAs
      reduced the target gene expression in a similar manner to the unmodified siRNA in
      cultured cells. These results suggest that the overhang modifications are
      tolerated for the siRNA activity.

PMID- 18066805
TI  - Synthesis of 9-fluorenemethyl boranophosphonodiphosphate via an H-phosphonate
      approach.
AB  - 9-Fluorenemethyl boranophosphonate 6 and its boranophosphonodiphosphate 7 were
      synthesized via an H-phosphonate approach. The method is efficient for the
      synthesis of acyclic compounds 6 & 7, and can be explored for the synthesis of
      nucleoside 5'-deoxy boranophosphonodiphosphate.

PMID- 18066806
TI  - Labeling of oligonucleotides with DTPA and DOTA on solid phase.
AB  - Oligonucleotide conjugates labeled with metal chelates of
      diethylenetriaminepentaacetic acid (DTPA) and tetraazacyclododecane-1,4,7,10
      tetraacetic acid (DOTA) were synthesized on solid phase using appropriate
      nucleosidic phosphoramidite building blocks (3, 4) and a modified deprotection
      metal chelation protocol. The major differences on the properties of the
      oligonucleotide conjugates also are discussed.

PMID- 18066807
TI  - Triplex formation-based artificial transcription factor to regulate target gene
      expression.
AB  - A triplex formation-based artificial transcription factor to recognize any
      upstream sequence of target genes was developed to regulate the target gene
      expression. The artificial transcription factor contains a single-stranded RNA to
      bind with duplex DNA of the upstream sequence of the target gene to form triplex,
      and an effecter domain, such as activation or repression domain, of transcription
      factor. Reporter beta-galactosidase activity in yeast was increased 1.5-2 times
      by introduction of the artificial transcription factor. The novel artificial
      transcription factor may be a useful tool to regulate the target gene expression
      and reveal unknown function of the target genes.

PMID- 18066808
TI  - Synthesis of aminomethyl- and bis-aminomethyl-fluorescein energy transfer
      terminators.
AB  - Synthesis of aminomethyl and bis-aminomethylfluorescein derived energy transfer
      terminators is described.

PMID- 18066809
TI  - 2-5A ligands--a new concept for the treatment of prostate cancer.
AB  - Several potent prostate specific membrane antigen (PSMA) inhibitors have been
      described recently. We generated a PSMA-specific 2-5A ligand called RBI 1033 by
      linking 2-5A to the N-acetylaspartylglutamate (NAAG)-based inhibitor ZJ-24. We
      measured the inhibitory activity of RBI 1033 to the folate hydrolase activity of
      PSMA. Amazingly, we found that compared to ZJ-24 (IC50 = 53.9 nM), RBI 1033 was
      more than 10 times more potent (IC50 = 4.78 nM) as a folate hydrolase inhibitor,
      while SMCC 2-5A lacking the ZJ-24 part, did not show much activity (IC50 = 1974
      nM). Also, RBI 1033's affinity to PSMA was found to be 10 times higher than ZJ-24
      itself.

PMID- 18066810
TI  - RNA cleavage by 2,9-diamino-1,10-phenanthroline PNA conjugates.
AB  - We report on the synthesis of 2,9-diamino-1,10-phenanthroline PNA conjugates as
      well as on their action in cleavage of a target RNA. Synthesis of the PNA
      conjugates are performed on solid support and the phenanthroline derivative is
      conjugated either to the amino-end or to a centrally positioned diaminopropionic
      acid in the PNA via a urea linker. Cleavage of the target RNA is achieved and
      compared to cleavage with the corresponding 2,9-dimethyl-1,10-phenanthroline and
      glycine conjugates.

PMID- 18066811
TI  - Solid support post-conjugation of amino acids and a phenanthroline derivative to
      a central position in peptide nucleic acids.
AB  - A solid phase synthesis strategy for post-conjugation of amino acids and a
      phenanthroline derivative to peptide nucleic acids is described. The peptide
      nucleic acids, synthesized by 9-fluorenylmethyloxycarbonyl chemistry on TentaGel
      S Rink Amide resin, have an internally placed unit carrying an amino linker with
      4-methyltrityl protection. Methyltrityl removal by mild acidic conditions and
      conjugation of amino acids or a phenanthroline derivative, via an amide or urea
      linker, was performed on-resin after completion of the chain assembly. This solid
      phase methodology resulted in excellent purities of the crude conjugates.

PMID- 18066812
TI  - Evaluation of lactam protection for synthesis of 2'-O-alkylated uridines.
AB  - Two different classes of protection for the uridine lactam function have been
      evaluated. These are benzoyl protections and different acetal functions. In
      particular the triisopropylsiloxymethyl protection is a most promising lactam
      protecting group for use in synthesis of 2'-O-alkyl-uridines.

PMID- 18066813
TI  - Synthesis of a 2'-O-(carbomoylmethyl)ribonucleoside H-phosphonate building block
      and a model dinucleotide.
AB  - In order to obtain higher quality 2'-O-carbamoylmethyl oligoribonucleotides we
      are conducting studies of this modification. Here we present synthesis of 2'-O
      carbamoylmethyl containing H-phosphonate building blocks as well as synthesis of
      model dinucleotides needed for these studies.

PMID- 18066814
TI  - Evaluating coupling procedures for synthesis of lna-Peptide conjugates.
AB  - As initial studies of block coupling of peptides with C-terminal glycines, we
      have evaluated of coupling of glycine building blocks under various conditions to
      a preassembled solid support bound LNA-fragment. Potentially competing side
      reaction have been studied and we have worked out a procedure for trifluoroacetyl
      protection of peptides.

PMID- 18066815
TI  - Synthesis of a branched locked nucleic acid (LNA) analogue.
AB  - A 3'-C-branched LNA-type bicyclic nucleoside, containing a furanose ring locked
      in an N-type conformation, was synthesized from a known 3-C-vinyl allofuranose
      derivative using a strategy relying on the condensation with the nucleobase after
      the introduction of the branching hydroxymethyl chain by our recently developed
      RuO4 based protocol. This branched LNA nucleoside has a potential as a monomer
      for the functionalization of LNA.

PMID- 18066816
TI  - 2'-O-hydroxyalkoxymethylribonucleosides and their incorporation into
      oligoribonucleotides.
AB  - A simple and efficient method for the preparation of pyrimidine 2'-O
      hydroxyethoxymethylribonucleosides and 2'-O-hydroxypropoxymethylribonucleosides
      has been developed. These modified nucleosides were incorporated into
      oligoribonucleotides, which were shown to form stable RNA/RNA duplexes. The
      effect of 2' -O-modification in the antisense and sense strands of small
      interference RNA was evaluated in multi-drug resistant NIH 3T3 cells.

PMID- 18066817
TI  - Improvement of the synthesis of sugar phosphonates using microwave irradiations.
AB  - Sugar and nucleoside phosphonates have been prepared using a microwave-assisted
      reaction. Results concerning optimization of the reaction for various substrates
      as well as comparison of thermal and microwave experimental conditions of the
      Michaelis-Arbuzov reaction is reported.

PMID- 18066818
TI  - Novel selective biocatalytic deacylation studies on key precursors for
      bicyclonucleosides.
AB  - Immobilized Candida antarctica lipase and Thermomyces lanuginosus lipase catalyze
      the deacylation of precursors of LNA analogs, 4'-C-acyloxymethyl-2',3',5'-tri-O
      acyl-beta-L-threo-pentofuranosylthymine and 4-C-acyloxymethyl-3,5-di-O-acyl-1,2-O
      (1-methylethylidene)-beta-L-threo-pentofuranose, respectively in a highly
      selective and efficient manner.

PMID- 18066819
TI  - Mass spectrometry based methods for analysis of nucleosides as antiviral drugs
      and potential tumor biomarkers.
AB  - The intracellular analysis of the phosphorylated metabolites of some anti-HIV
      nucleosides by liquid chromatography or capillary electrophoresis coupled with
      tandem mass spectrometry (LC-MS/MS or CE-MS/MS) has been realized on human
      peripheral blood mononuclear cells (PBMC), with limit of quantitation (LOQ) that
      allow them to be quantitated intracellularly. We described also the analysis of
      modified urinary nucleosides as potential tumor biomarkers.

PMID- 18066820
TI  - Two carbocyclic locked nucleic acid analogues give structural information about
      the role of hydration in A-type duplexes.
AB  - Two locked nucleic acid (LNA) analogues with three-carbon 2'-4' linkages,
      saturated or unsaturated, are synthesized using a ring-closing metathesis based
      strategy. Strongly stabilized duplexes with complementary RNA and slightly
      destabilized duplexes with complementary DNA are observed. CD-spectroscopy
      indicates a less pronounced shift toward A-type duplexes compared to LNA. These
      results combining a strong N-type conformation with the absence of a 2'-oxygen
      demonstrate a stronger importance of minor groove hydration in an intermediate
      duplex type than in an A-type duplex.

PMID- 18066821
TI  - Porphyrin-DNA: a supramolecular scaffold for functional molecules on the
      nanometre scale.
AB  - We are pursuing the aim to use DNA as a supramolecular scaffold for the creation
      of electronically functional molecules on the nanometre scale. Here, we give a
      review on our results on porphyrin modified nucleotides used for this purpose. A
      general synthetic route to porphyrin-nucleotides has been devised, and the
      building blocks can be incorporated into oligonucleotides using standard solid
      phase synthesis methods. Up to 11 porphyrins were incorporated into DNA, reaching
      a length of approximately 4 nm in the array. The spectroscopic data are
      consistent with a porphyrin induced secondary structure stabilisation in the
      single strands.

PMID- 18066822
TI  - New pseudonucleosides containing chiral oxazolidin-2-ones and cyclosulfamides as
      aglycones: synthesis and antiviral evaluation.
AB  - A series of chiral cyclosulfamides and oxazolidinon-2-ones have been synthesized
      starting from aminoacids. Regioselective substitution of these pseudopyrimidic
      heterocyles was carried out under Mitsunobu conditions. Best substitution results
      were obtained by preliminary deprotection of cyclosulfamides and their
      condensation with beta-D-ribofuranose. Chiral oxazolidin-2-ones were coupled
      directly with D-ribofuranose. All compounds were tested against HSV-2, VV and SV
      viruses. Two compounds 6b and 6e showed significant activities against HSV-type
      1.

PMID- 18066823
TI  - 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine: a nucleoside reverse transcriptase
      inhibitor with highly potent activity against wide spectrum of HIV-1 strains,
      favorable toxic profiles, and stability in plasma.
AB  - Working hypotheses to solve the critical problems of the existing highly active
      anti-retroviral therapy were proposed. The study based on the hypotheses proved
      the validity of the hypotheses and resulted in the development of 2'-deoxy-4'-C
      ethynyl-2-fluoroadenosine, a nucleoside reverse transcriptase inhibitor, with
      highly potent activity against all HIV-1, very favorable toxic profiles, and
      stability in plasma. The nucleoside will prevent or delay the emergence of drug
      resistant HIV-1 variants and be an ideal therapeutic agent for both HIV-1 and HBV
      infections.

PMID- 18066824
TI  - NMR study of ammonium ion binding to d[G3T4G4]2 and d[G4(T4G4)3] G-quadruplexes.
AB  - Quantitative NMR study has shown a significant difference in affinity of
      (15)NH(4)(+) ions for cation binding sites within G-quadruplexes adopted by
      d[G3T4G4]2 and d[G4(T4G4)3].

PMID- 18066825
TI  - Antiviral activity of 3-(3,5-dimethylbenzyl)uracil derivatives against HIV-1 and
      HCMV.
AB  - Antiviral activity of 1,3-disubstituted uracil derivatives was evaluated against
      HIV-1 and HCMV. It appears that the nitrogen of the 1-cyanomethyl group is
      important for anti-HIV-1 activity, suggesting interaction with the amino acid
      residues of HIV-1 reverse transcriptase. 1-Arylmethyl derivatives also exhibited
      good anti-HIV-1 activity; and that of the 2- and 4-picolyl derivatives was
      particularly excellent.

PMID- 18066826
TI  - Sequence-specific recognition of double-stranded DNA by synthetic minor groove
      binder conjugates. toward the construction of artificial site-specific
      deoxyribonucleases.
AB  - Bis-conjugates of hairpin N-methylpyrrole/N-methylimidazole oligocarboxamide
      minor groove binders (MGB) possessing enhanced affinity and sequence-specificity
      for dsDNA were synthesized. Two hairpin MGBs were connected by their N-termini
      via an aminodiacetate linker. The binding of bis-MGB conjugates to the target DNA
      was studied by gel mobility retardation, footprinting, and circular dichroism;
      their affinity and binding mode in the DNA minor groove were determined. In order
      to functionalize the bis-MGB conjugates, DNA-cleaving agents such as
      phenanthroline or bipyridine were attached. Effective site-specific cleavage of
      target DNA in the presence of Cu(2+) ions was observed.

PMID- 18066827
TI  - Design, synthesis, and anti-tumor activity of 4'-thionucleosides as potent and
      selective agonists at the human A3 adenosine receptor.
AB  - On the basis of potent and selective binding affinity of Cl-IB-MECA to the human
      A(3) adenosine receptor, its 4'-thioadenosine derivatives were efficiently
      synthesized starting from D-gulonic gamma-lactone. Among compounds tested, 2
      chloro-N(6)-(3-iodobenzyl)- and 2-chloro-N(6)-methyl-4' -thioadenosine-5' 
      methyluronamides (7a and 7b) exhibited nanomolar range of binding affinity (K(i)
      = 0.38 nM and 0.28 nM, respectively) at the human A(3)AR. These compounds showed
      anti-growth effects on HL-60 leukemia cell, which resulted from the inhibition of
      Wnt signaling pathway.

PMID- 18066828
TI  - Mismatch discrimination of base-modified nucleic acids and their constituents:
      non-Watson-Crick base pairing induced by tautomerization.
AB  - The effect of tautomerism on the mismatch discrimination was studied on 7
      deazapurine and 8-aza-7-deazapurine analogues of isoguanosine. 7-Halogenated 7
      deaza-2'-deoxyisoguanosines show better base pair discrimination than 2'
      deoxyisoguanosine due to the more favored keto tautomer formation. 8-Aza-7
      deazaisoguanosine and its 7-halogeno derivatives also show higher keto tautomer
      population than that of isoguanosine, but the 7-halogens do not bias the
      tautomeric equilibrium significantly as it is observed for the 7-deaza-2'
      deoxyisoguanosine derivatives.

PMID- 18066829
TI  - Novel fluorophores for labeling of nucleosides and oligonucleotides.
AB  - Five novel fluorophores have been synthesized and their comparative fluorescence
      has been studied in different organic solvents and aqueous solutions of inorganic
      ions. Out of these, two highly sensitive fluorophores have been used to label
      phosphoramidites and oligodeoxyribonucleotides. The fluorescently labelled
      amidites and oligodeoxyribonucleotides showed good fluorescence signals.

PMID- 18066830
TI  - Oligonucleotide conjugate GRN163L targeting human telomerase as potential
      anticancer and antimetastatic agent.
AB  - Telomerase is one of the key enzymes responsible for the proliferative
      immortality of the majority of cancer cells. We recently introduced a new
      telomerase inhibitor, a 13-mer oligonucleotide N3' --> P5'-thio-phosphoramidate
      lipid conjugate, designated as GRN163L. This compound inhibits telomerase
      activity in various tumor cell lines with IC(50) values of 3-300 nM without any
      cellular uptake enhancers. GRN163L demonstrated potent and sequence specific anti
      cancer activity in vivo in multiple animal models. This compound was able to
      significantly affect not only the growth of primary tumors, but also the spread
      and proliferation of metastases. GRN163L is currently in Phase I and Phase I/II
      clinical studies in patients with solid tumors and CLL, respectively.

PMID- 18066831
TI  - DNA labelling topologies for monitoring DNA-protein complex formation by
      fluorescence anisotropy.
AB  - In this work, fluorescence anisotropy was used to study DNA binding of the DNA
      methyltransferase M.TaqI. For this purpose short DNA molecules labelled with
      three different fluorophores (Cy3, thiazole orange, and ethidium bromide) were
      prepared in various topologies and their suitability for detection of DNA-protein
      complex formation was investigated.

PMID- 18066833
TI  - Biophysical stability and enzymatic recognition of oxanine in DNA.
AB  - Oxanine (Oxa), which is one of the major products generated from guanine by
      nitrosative oxidation and is as long-lived as Gua in DNA, has been thought to be
      one of the major causes for NO-induced DNA damage. In the present study, using
      several synthetic Oxa-containing oligodeoxynucleotides, biophysical stability and
      enzymatic recognition of Oxa was investigated in DNA strands. It was found that
      Oxa did not mediate marked distortion in the whole DNA structure although Oxa
      pairing with 4 normal bases decreased thermal stability of the DNA duplexes
      compared to Gua:Cyt base pair. Regarding the responses of the DNA-relevant
      enzymes to Oxa, it was determined that Oxa was recognized as Gua except that DNA
      polymerases incorporated Thy as well as Cyt opposite Oxa. These results imply
      that Oxa tends to behave as a kind of naturally occurring base, Gua and
      therefore, would be involved in the genotoxic and cytotoxic threats of NO in
      cellular system.

PMID- 18066832
TI  - Thiazole orange: a useful probe for fluorescence sensing of G-quadruplex-ligand
      interactions.
AB  - Fluorimetric titrations were performed to gain insight into parameters that
      govern the association of thiazole orange (TO) and G-quadruplex-DNA (G4-DNA). Use
      of loop-containing and loop-lacking quadruplexes evidenced the critical influence
      of the loops on the stoichiometry of the association and on the fluorescence
      exaltation of TO. We subsequently tried to benefit from this sensitivity to
      evaluate the influence of G4-DNA cationic environment on ligand binding via a
      recently reported G4-FID assay.

PMID- 18066834
TI  - Synthesis and properties of pyrrolidine-based negatively charged DNA mimics.
AB  - A set of novel chiral pyrrolidine-based nucleotide mimics, in which nucleobase,
      hydroxyl group and phosphonic acid residue were attached to different carbon
      atoms of the pyrrolidine ring, was synthesized. These monomers were used for the
      synthesis of the corresponding oligomers, and their physico-chemical properties
      were evaluated.

PMID- 18066835
TI  - 5-methylcytosine-selective osmium oxidation.
AB  - Methylcytosine was efficiently and easily modified through osmium oxidation.
      Methylcytosine-selective oxidation is applicable to detection of the cytosine
      methylation status at a specific site of a long sequence using the formation of a
      bulge structure by hybridization with a guide DNA.

PMID- 18066836
TI  - A flexible method for the fabrication of gold nanostructures using
      oligonucleotide derivatives.
AB  - Several linear and branched DNA structures from 80-200 nm with a biotine molecule
      in the middle have been prepared. These structures have been decorated by
      addition of positively charged gold nanoparticles carrying 4
      (dimethylamino)pyridine ligands. Streptavidin binds to the central biotine
      molecule introducing a 20 nm gap in the structure in which a biotinylated
      nanoparticle can be introduced. The simplest structure (80 nm, linear) is formed
      by 4 oligonucleotides. By changing some of these components changes on length,
      shape, and recognition system easily can be introduced.

PMID- 18066837
TI  - 2'-deoxyadenosine bearing hydrophobic carborane pharmacophore.
AB  - Modification of 2'-deoxyadenosine at position 8 with para-carborane boron cluster
      is described. Incorporation of boron cluster into nucleic base has been
      accomplished using Sonogashira palladium-catalyzed cross-coupling reaction or,
      alternatively, Huisgen "click" type reaction. These are the first examples of
      adenosine derivatives with hydrophobic carborane pharmacophore attached to purine
      base.

PMID- 18066838
TI  - Highly effective non-explosive activators based on saccharin for the synthesis of
      oligonucleotides and phosphoramidites.
AB  - A new class of non-explosive activators has been developed based on heterocyclic
      tertiary amine salts of saccharin. These salts have been found to be highly
      effective in the synthesis of oligonucleotides and nucleoside phosphoramidites.

PMID- 18066839
TI  - In vivo and in vitro activity and mechanism of action of the multidrug cytarabine
      L-glycerylyl-fluorodeoxyuridine.
AB  - Multidrugs have the potential to bypass resistance. We investigated the in vitro
      activity and resistance circumvention of the multidrug cytarabine-L
      fluorodeoxyuridine (AraC-L-5FdU), linked via a glycerophospholipid linkage.
      Cytotoxicity was determined using sensitive (A2780, FM3A/0) and resistant
      (AG6000, AraC resistant, deoxycytidine kinase deficient; FM3A/TK-, 5FdU
      resistant, thymidine kinase deficient) cell lines. Circumvention of nucleoside
      transporter and activating enzymes was determined using specific inhibitors, HPLC
      analysis and standard radioactivity assays. AraC-L-5FdU was active (IC50: 0.03
      microM in both A2780 and FM3A/0), had some activity in AG6000 (IC50: 0.28
      microM), but no activity in FM3A/TK(-) (IC50: 18.3 microM). AraC-nucleotides were
      not detected in AG6000. 5FdU-nucleotides were detected in all cell lines. AraC-L
      5FdU did not inhibit TS in FM3A/TK(-) (5%). Since phosphatase/nucleotidase
      inhibition reduced cytotoxicity 7-70-fold, cleavage seems to be outside the cell,
      presumably to nucleotides, and then to nucleosides. The multidrug was orally
      active in the HT-29 colon carcinoma xenografts which are resistant toward the
      single drugs.

PMID- 18066840
TI  - 2',4'-BNA(NC): a novel bridged nucleic acid analogue with excellent hybridizing
      and nuclease resistance profiles.
AB  - Oligonucleotides modified with 2 ',4 '-BNA(NC) (N-H)/(N-Me) monomers exhibited
      excellent hybridizing and nuclease resistance properties. Duplex and triplex
      thermal stabilities were greatly enhanced by incorporating 2',4'-BNA(NC) (N-H)
      and (N-Me) monomers and nuclease resistance was tremendously higher than that of
      natural oligonucleotide.

PMID- 18066841
TI  - Mass spectrometry of oligonucleotides.
AB  - Expanding research in the field of modified oligonucleotides demands suitable
      analytical tools for size and purity verification of known compounds and accurate
      structure elucidation of unknowns. There is a need for characterization of the
      types and sites of modifications in oligonucleotides and to identify and sequence
      selected candidates originating from synthesis. The potential of electrospray
      tandem mass spectrometry (ESI-MS/MS) for structural characterization and
      sequencing of oligonucleotides is demonstrated. The fundamental behavior of DNA,
      RNA, and selected modified oligonucleotides in gas-phase is shown. Since gas
      phase dissociation does not demand specific structural prerequisites, the method
      bears a great potential for rapid and most accurate characterization of modified
      oligonucleotides, e.g. from combinatorial libraries.

PMID- 18066842
TI  - Mismatch base pair detection by fluorescence spectral change upon addition of
      metal cation--toward efficient analysis of single nucleotide polymorphism.
AB  - Addition of mercury (II) cation to fluorescent-labeled duplex involving a T:T
      mismatch base pair and silver (I) cation to fluorescent-labeled duplex involving
      a C:C mismatch base pair significantly changed the fluorescence intensity, but no
      significant change in the fluorescence intensity was observed for duplexes
      involving the other base pairs. The fluorescence spectral change upon addition of
      the metal cation can discriminate T:T and C:C mismatch base pairs from the other
      base pairs. Our results certainly support the idea that the fluorescence spectral
      change upon addition of the metal cation could be a convenient strategy for the
      mismatch base pair detection by the heteroduplex analysis, and may eventually
      lead to progress in single nucleotide polymorphism genotyping.

PMID- 18066843
TI  - The effect of INA [(R)-1-O-(1-pyrenylmethyl)glycerol] insertions on the structure
      and biological activity of a G-quadruplex from a critical KRAS G-rich sequence.
AB  - Quadruplex-forming oligonucleotides containing INA [(R)-1-O-(1
      pyrenylmethyl)glycerol] insertions have been designed and studied for their
      capacity to inhibit the expression of the KRAS oncogene in pancreatic
      adenocarcinoma cells. It is found that INA can influence the folding topology of
      the G-quadruplex. The oligonucleotides forming the most stable G-quadruplex (ODN
      637) is found to exhibit the highest bioactivity.

PMID- 18066844
TI  - Attachment of cholesterol to amino-LNA: synthesis and hybridization properties.
AB  - Here, we present our synthesis of amino-LNA with a C6-linker and hybridization
      studies of these. A cholesterol moiety was attached at the end of the C6-linker.
      This resulted in drastic drops against DNA of the modified oligonucleotide.

PMID- 18066845
TI  - Solid phase synthesis of nucleobase and ribose modified inosine nucleoside
      analogues.
AB  - The synthesis and the use of new N-1-dinitrophenyl-inosine based solid support is
      reported. The support, which binds the nucleoside by a 5'-O-monomethoxytrityl
      function, reacting with N-nucleophiles allowed the synthesis of a small library
      of N-1 alkylated inosine and AICAR derivatives. Moreover, the obtained supports,
      after the cleavage of the 2' -3' ribose bond, furnished a set of new N-1
      alkylated-2' -3' -secoinosine derivatives in high yields.

PMID- 18066846
TI  - Asymmetric synthesis and biological activity of L-bicyclocarba-d4T.
AB  - Novel L-bicyclocarba-d4T (1), an enantiomer of D-N-MCd4T has been enantiopurely
      synthesized as a potent anti-HIV agent starting from (R)-epichlorohydrin using
      tandem alkylation, chemoselective reduction of ester in the presence of lactone
      functional group, Grignard reaction, RCM reaction, and Mitsunobu reaction as key
      steps. L-N-MCd4T (1) was found to be very potent anti-HIV-1 (EC(50) = 6.76
      microg/mL) agent with no cytotoxicity.

PMID- 18066847
TI  - Homogeneous fluorescence assays for RNA diagnosis by pyrene-conjugated 2'-O
      methyloligoribonucleotides.
AB  - We developed a bispyrene-conjugated 2'-O-methyloligoribonucleotide as an RNA
      specific RNA-probe. The probe hybridized with the complementary RNA, greatly
      enhancing fluorescence and discriminating RNA from DNA. The assay was carried out
      in homogeneous aqueous media without removing the unbound probe from the
      detection solution. This homogeneous fluorescence assay also discriminated
      mismatch sequences in the target RNA. These pyrene probes could possess high
      potential to detect RNA in biological specimens simply.

PMID- 18066848
TI  - A simple nucleic acid alternative: aminopropyl nucleic acids (APNAs).
AB  - Aminopropyl nucleic acids are constitutionally simple nucleic acids alternatives
      with one chiral center per nucleotide and with the constitutional potential to
      hybridize with RNA. Both R and S isomers of the 3'-or 2'-aminopropyl nucleosides
      were incorporated either into DNA or likewise were used for fully modified
      sequences. The (R)-adenine analogue, yielding (S)-APNA, can be considered as a
      candidate for universal base pairing.

PMID- 18066849
TI  - Detection of terminal mismatches on DNA duplexes in homogeneous assays or with
      immobilized probes.
AB  - We recently reported the design of new fluorescent oligo-2'-deoxyribonucleotides
      (FODNs) for the detection of terminal mismatches on DNA duplexes in homogeneous
      assays. We now report the validation of this method in homogeneous assays with
      other sequences and the feasibility of the detection of terminal mismatches with
      immobilized FODNs. In all cases studied, the mismatched duplexes were more
      fluorescent than the perfect ones and results confirmed that the discrimination
      factor is sequence-dependent.

PMID- 18066851
TI  - The 6-methoxymethyl derivative of pyrrolo-dC for selective fluorometric detection
      of guanosine-containing sequences.
AB  - The beta-cyanoethyl phosphosphoramidite derivatives of 6-methyl- and 6
      methoxymethyl-3-(2-deoxy-beta-D-ribofuranosyl)-3H-pyrrolo[2,3-d]pyrimidin-2-one
      have been synthesized. These monomers have been employed for oligodeoxynucleotide
      synthesis to evaluate their effect on duplex stability and ability to
      fluorometrically report on hybridization. The structurally conservative 6
      methoxymethyl-substitution results in a pyrrolocytidine that is stabilizing
      toward hybrid formation (Delta Tm = +1.3 degrees C) whereas the known 6
      methylpyrrolocytidine is destabilizing (Delta Tm = -4.7 degrees C), in the
      sequence examined. The 6-methoxymethylpyrrolocytidine retains excellent mismatch
      discrimination and its fluorescence is selectively quenched when hybridized to a
      match oligodeoxynucleotide sequence. The quenching of fluorescence for an
      internal position is approximately three-fold, whereas a terminal position (5'
      end or 3'-end) experienced approximately two-fold decrease in the fluorescence
      intensity.

PMID- 18066852
TI  - Synthesis and biological activity of phosphonocarboxylate DNA.
AB  - Oligodeoxynucleotides containing internucleotide phosphonoacetate esters are
      taken up irreversibly by cells in culture in the absence of cationic lipids.
      These oligonucleotides also are active in stimulating RNase H and are stable
      toward nucleases.

PMID- 18066853
TI  - Synthetic use of epoxy-sugar nucleosides.
AB  - Preparation of 1',2 '-, 3 ',4 '-, and 4 ',5 '-epoxy derivatives of nucleosides
      and their use for the stereoselective synthesis of 1'- and 4 '-branched analogues
      are described.

PMID- 18066854
TI  - Stabilization of multi-stranded nucleic acid structures using 3'-S
      phosphorothiolate linkages.
AB  - 3 '-S-Phosphorothiolate linkages incorporated into an oligodeoxynucleotide have
      been shown to stabilise duplex formation with a complementary RNA strand, but
      destabilise a duplex formed with a complementary DNA strand. The four-stranded i
      motif structure is also stabilised this modification.

PMID- 18066855
TI  - Florobenzene as artificial nucleobases-base pairing and stacking interactions.
AB  - Base stacking is a complicated and not completely understood phenomenon that is
      influenced by contributions of electrostatic (dipole-dipole and dipole-induced
      dipole) interactions, dispersion (permanent dipole-induced dipole) effects and
      solvation effects. The plots of those factors did not show qualitative
      correlation (Guckian et al., J. Am. Chem. Soc. 1996, 118, 8182-8183). We tried to
      correlate the stacking and solvation contributions with lipophilicity, extent of
      fluorine substitution and dipole moment.

PMID- 18066856
TI  - Some novel aminopropyl nucleoside phosphonates.
AB  - The aminopropyl nucleoside phosphonates 1-3 have an amino function within either
      the acyclic chain (series 2 and 3) or as substituent (series 1) of HPMPC
      (Cidofovir). Both purine and pyrimidine nucleoside anologs have been synthesized.
      In contrast to HPMPC, only a weak antiherpes virus activity could be demonstrated
      for 2b and 2c.

PMID- 18066857
TI  - Reactions of malonaldehyde and acetaldehyde with calf thymus DNA: formation of
      conjugate adducts.
AB  - Our previous work has shown that treatment of nucleosides with malonaldehyde
      simultaneously with acetaldehyde affords stable conjugate adducts. In the present
      study we demonstrate that conjugate adducts are also formed in calf thymus DNA
      when incubated with the aldehydes. The adducts were identified in the DNA
      hydrolysates by their positive ion electrospray MS/MS spectra, by coelution with
      the 2'-deoxynucleoside standards, and, in the case of adducts exhibiting
      fluorescent properties, also by LC using a fluorescence detector. In the
      hydrolysates of double-stranded DNA (ds DNA), two deoxyguanosine and two
      deoxyadenosine conjugate adducts were detected and in single-stranded DNA (ss
      DNA) also, the deoxycytidine conjugate adduct was observed. The guanine base was
      the major target for the malonaldehyde-acetaldehyde conjugates and 2'
      deoxyguanosine adducts were produced in ds DNA at levels of 100-500 adducts/10(5)
      nucleotides (0.7-3 nmol/mg DNA).

PMID- 18066858
TI  - Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides
      and their prodrugs: a comparison of phosphonates and corresponding nucleosides.
AB  - Cyclic phosphonomethoxy pyrimidine nucleosides that are bioisosteres of the
      monophosphate metabolites of HIV reverse transcriptase (RT) inhibitors AZT, d4T,
      and ddC have been synthesized. The RT inhibitory activities of the phosphonates
      were reduced for both dideoxy (dd) and dideoxydidehydro (d4) analogs compared to
      the nucleosides. Bis-isopropyloxymethylcarbonyl (BisPOC) prodrugs were prepared
      on selected compounds and provided > 150-fold improvements in antiviral activity.

PMID- 18066859
TI  - In vitro anti-malarial activity of N6-modified purine analogs.
AB  - A library of N6-hydroxy-, methoxy-, or amino-adenosine analogs was prepared and
      screened for anti-malarial properties. We found three compounds that possess anti
      plasmodial activity in the low micromolar range against the multi-drug resistant
      VS1 strain, namely N6-hydroxy-9H-purin-6-amine (IC50 5.57 micro M), 2-amino-N6
      amino-adenosine (IC50 12.2 micro M), and 2-amino-N6-amino-N6-methyladenosine
      (IC50 0.29 micro M). More importantly, the compounds were non-toxic, with 2-amino
      N6-amino-N6-methyladenosine showing a selectivity index of 5008.

PMID- 18066860
TI  - Rearranging the bicyclo[3.1.0]hexane template of carbocyclic nucleosides to
      improve binding recognition by kinases.
AB  - A novel bicyclo[3.1.0]hexane carbocyclic nucleoside (4) with a south-like
      conformation amenable to interact with the herpes thymidine kinase (HSV-tk) was
      synthesized with an endo-hydroxyl group positioned at the tip of the
      bicyclo[3.1.0]hexane ring system opposite to the tip of the fused cyclopropane
      ring. The introduction of the hydroxymethyl chain through a Baylis-Hillman type
      reaction and the regioselective opening of a cyclic sulfite intermediate to
      introduce the nitrogen functionality at the correct position are highlighted.

PMID- 18066861
TI  - Hydration regulates the thermodynamic stability of DNA structures under molecular
      crowding conditions.
AB  - Although water is an integral part of DNA structures, the effects of water
      molecules on various DNA structures which are formed by not only Watson-Crick but
      also Hoogsteen base pairs are still unclear. Here, we studied quantitatively the
      effects of molecular crowding on the thermodynamics of a parallel G-quadruplex
      formation of [d(TG 4)2]4 with Hoogsteen base pairs. It was demonstrated that
      molecular crowding conditions stabilized the parallel G-quadruplex. Moreover, the
      plot of stability of the parallel G-quadruplex structure versus water activity
      suggested that water molecules were released through the G-quadruplex formation.
      The stabilization of the DNA structures consisting of Hoogsteen base pairs under
      cell-like conditions may lead to a structural polymorphism of various DNA
      sequences regulated by water molecules.

PMID- 18066862
TI  - Nucleosides and oligonucleotides with diynyl side chains: the huisgen-sharpless
      cycloaddition "click reaction" performed on DNA and their constituents.
AB  - Phosphoramidite building blocks related to the four canonical DNA constituents
      and oligonucleotides with octadiynyl side chains (5b-8b) or dipropargyl ether
      residues (5c) were synthesized. Nucleosides and oligonucleotides were
      functionalized at the terminal triple bonds employing the Huisgen-Sharpless
      cycloaddition "click reaction."

PMID- 18066863
TI  - An efficient synthesis of 7-functionalized 7-deazapurine beta-D- Or beta-L
      ribonucleosides: glycosylation of pyrrolo[2,3-D]pyrimidines with 1-O-acetyl-2,3,5
      tri-O-benzoyl-D-Or L-ribofuranose.
AB  - The glycosylation reaction performed with 7-halogenated 7-deazapurines employing
      commercially available 1-O-acetyl-2,3,5-tri-O-benzoyl-D- or L-ribofuranoses is
      described.

PMID- 18066864
TI  - Fluorinated 7-deazapurine 2'-deoxyribonucleosides: modification at the nucleobase
      and the sugar moiety.
AB  - 7-Deaza-7-fluoro-purine 2'-deoxynucleosides as well as 2'-deoxy-2'
      fluoroarabinofuranosyl nucleosides 1-8 were synthesized. The fluorine atom was
      introduced on the base level with Selectfluor. Nucleobase-anion glycosylation was
      then employed to form the nucleosides. Properties of the fluorine compounds were
      studied in solution and in solid state. Compound 4a was incorporated into
      oligonucleotides where the stabilizing effect was observed.

PMID- 18066865
TI  - Foldamers derived from nucleoside beta-amino acids: PNA Or DNA? Can we have both
      in one place?
AB  - The synthesis of a modified thymidine (nucleoside beta-amino acid) monomer and
      preliminary investigations into the solid phase peptide synthesis of PNA/DNA
      chimeras containing a neutral, internucleoside amide linkage are described.

PMID- 18066866
TI  - Synthesis of the bicyclo-[4.3.0]-thymidyl-nucleoside via pd(II)-mediated ring
      expansion chemistry.
AB  - A variety of modified nucleosides to improve antisense oligodeoxynucleotide
      properties such as target affinity, nuclease resistance, and pharmacokinetics
      were developed in the last two decades. In the context of conformational
      restriction we present here the synthesis of the [4.3.0]-bicyclo-DNA thymine
      monomer via Pd(II)-mediated ring expansion of an intermediate of the tricyclo-DNA
      synthesis.

PMID- 18066867
TI  - Efficient synthesis of thymidine boranophosphoramidates conjugated with amino
      acids.
AB  - An efficient synthesis of a thymidine boranophosphoramidate prodrug was
      accomplished using a phosphoramidite approach in high yield. This new class of
      compounds is designed to have improved antiviral and anticancer advantages
      conferred by combining the boranophosphate and normal nucleoside amino acid
      phosphoramidate. Compounds were characterized by MS and 31P NMR.

PMID- 18066868
TI  - Novel non-nucleoside human cytomegalovirus inhibitors based upon TSAO nucleoside
      derivatives: structure-activity relationships.
AB  - TSAO derivatives are a unique group of potent and highly specific inhibitors of
      HIV-1 replication. We have recently reported 4''-ureido TSAO derivatives that are
      devoid of anti-HIV-1 activity, but inhibit human cytomegalovirus with an activity
      comparable to that of Ganciclovir. We herein report the synthesis and biological
      evaluation of novel 4''-ureido TSAO derivatives in order to evaluate the
      structural features required for anti-HCMV activity. Interestingly, these studies
      revealed that the compounds may inhibit HCMV at the DNA polymerase step via a non
      nucleoside mechanism.

PMID- 18066869
TI  - Methylation-dependent fragment separation: novel analysis of 5-methyl cytosine by
      capillary electrophoresis of amplified DNA using PCR incorporation of chemically
      modified dCTP.
AB  - Methylation of the cytosine (C) ring to form 5-methyl cytosine (MeC) in normally
      unmethylated CpG-rich regions of promoters in genes is associated with
      transcriptional silencing. Quantification of MeC is of current interest in
      findining new biomarkers for cancer. To this end, and for basic research in
      epigenomics, we have investigated a new method for relatively simple measurement
      of MeC content by capillary electrophoresis (CE). PCR amplicons for CE analysis
      are generated from bisulfite-converted DNA [C --> uracil (U)] using fluorescently
      labeled primers that anneal independent of methylation status. Resultant
      incorporation of C vs. T at original MeC vs. C positions can lead to separate CE
      peaks for signal integration that is proportional to MeC content. Furthermore,
      these PCR products are suitable for additional methylation analyses by
      sequencing, single-base extension, or TaqMan. Interestingly, PCR using alpha 
      thio-dCTP led to greater CE separations.

PMID- 18066870
TI  - Discovery of ANA975: an oral prodrug of the TLR-7 agonist isatoribine.
AB  - ANA975, a 5-amino-3-beta -D-ribofuranosyl-3H-thiazolo[4,5-d]pyrimidin-2-one
      derivative, was synthesized in the search of an oral prodrug of isatoribine, a
      small molecule toll-like receptor 7 (TLR-7) agonist. Several strategies were
      studied to enable the kilogram-scale synthesis of ANA975. Three general total
      syntheses are described. In the phase I clinical study of ANA975 against
      hepatitis C virus (HCV), conversion to isatoribine in plasma was rapid and
      effective, delivering levels of isatoribine that have been shown to be clinically
      relevant.

PMID- 18066871
TI  - Aryl-containing esters of triphosphoric acid as substrates of terminal
      deoxynucleotidyl transferase.
AB  - A new group of terminal deoxynucleotidyltransferase (TDT) substrates, namely, non
      nucleoside triphosphates (NNTP) bearing 5-substituted 2,4-dinitrophenyl fragments
      instead of nucleoside residues was synthesized.

PMID- 18066872
TI  - Selective fluorescence detection of 8-oxoguanosine with 8-oxoG-clamp.
AB  - 8-oxoguanosine, which is derived from the oxidation of guanosine (dG), is known
      to induce transversion mutations (G:C-->T:A) in DNA. The compounds with a small
      molecular weight for recognizing 8-oxoG were designed on the basis of the
      structure of the G-clamp, which is reported to have selective affinity toward
      guanosine. The G-clamp derivatives with the additional binding units toward 8
      oxoG were effectively synthesized and named "8-oxoG-clamps." The 8-oxoG-clamp
      completely discriminated 8-oxoG from other nucleosides by fluorescence quenching.

PMID- 18066873
TI  - IMPDH as a biological probe for RNA antiviral drug discovery: synthesis,
      enzymology, molecular docking, and antiviral activity of new ribonucleosides with
      surrogate bases.
AB  - Our interest in the discovery of molecules with antiviral activity against RNA
      viruses led us to the design of ribonucleosides with surrogate bases with the
      intent of using inhibition of inosine monophosphate dehydrogenase (IMPDH) as a
      probe for antiviral drug discovery. A general methodology for the preparation of
      these compounds is discussed. Kinetic parameters of the inhibition studies with
      IMPDH, which were carried out spectrophotometrically by monitoring the formation
      of NADH, are given. Antiviral information and correlation of activity with IMPDH
      inhibition are discussed.

PMID- 18066874
TI  - The synthesis of EPR differentiable spinlabels and their coupling to uridine.
AB  - For EPR measurements of RNA, DNA, or proteins, the occurrence of the paramagnetic
      species is necessary. The aim of this work is to improve the synthesis of two
      different EPR spinlabels 2,2,6,6-tetra methyl-3,4-dehydro-piperidin-N-oxyl-4
      acetylene (TEMPA) 6 and 15N-labeled TEMPA 6* and their coupling to uridine. The
      yield of the synthesis of TEMPA could be increased to 40% and the second
      nitroxide 2,2,6,6-tetramethyl-3,4-dehydro-piperidin-15N-oxyl-4-acetylene 6* could
      be synthesized with a yield of 11%.

PMID- 18066875
TI  - PNA conjugated to high-molecular weight poly(ethylene glycol): synthesis and
      properties.
AB  - The conjugation of a bioactive, fluorescent PNA sequence to high-molecular weight
      poly(ethylene glycol) (PEG) is described and the properties of the PEG-PNA
      conjugate are evaluated.

PMID- 18066876
TI  - Biologically-validated HIV integrase inhibitors with nucleobase scaffolds:
      structure, synthesis, chemical biology, molecular modeling, and antiviral
      activity.
AB  - Integrase, an enzyme of the pol gene of HIV, is a significant viral target for
      the discovery of anti-HIV agents. In this presentation, we report on the
      continuation of our work on the discovery of diketo acids, constructed on
      nucleobase scaffolds, that are inhibitors of HIV integrase. An example of our
      synthetic approach to inhibitors with purine nucleobase scaffolds is given.
      Comparison is made between integrase inhibition data arising from compounds with
      pyrimidine versus purine nucleobase scaffold. Antiviral results are cited.

PMID- 18066877
TI  - Biophysical properties of quadruplexes containing two or three 8
      bromodeoxyguanosine residues.
AB  - A physico-chemical characterization, based on NMR and CD spectroscopy, of
      quadruplexes formed by the oligonucleotide d(TGGGT), where two or three Gs are
      substituted by 8-bromo-2'-deoxyguanosine residues (dGBr), is reported. The
      oligonucleotidic sequences d(TGBr GBr GT), d(TGBr GGBr T), d(TGGBr GBr T), and
      d(TGBr GBr GBr T) have been synthesized. Only sequences d(TGBr GGBr T) and d(TGBr
      GBr GT) were able to fold into a well defined quadruplex structure, and their CD
      profiles and thermal stabilities turned out to be very different from those
      observed for the natural counterpart, indicating that the 8-Br-dG residues
      dramatically affect the structure of the quadruplex.

PMID- 18066878
TI  - Effect of the incorporation of 2'-deoxy-8-(hydroxyl)adenosine on the stability of
      quadruplexes formed by modified human telomeric DNA.
AB  - Differential scanning calorimetry (DSC) and circular dichroism (CD) techniques
      were used to investigate the physico-chemical properties of the quadruplexes
      formed by the two different truncations of human telomeric sequence d(TAGGGT) and
      d(AGGGT), where the adenines were substituted by 2'-deoxy-8-(hydroxyl)adenosine
      (A --> A OH). CD spectra show that the modified sequences are able to form
      parallel-stranded quadruplex structure. Analysis of the thermodynamic parameters
      reveals that the introduction of the modified adenine affects in different way
      the thermal stability of the [d(TAGGGT)]4 and [d(AGGGT)]4 quadruplexes.

PMID- 18066879
TI  - Synthesis of new, base-modified PNA monomers.
AB  - A number of N-Boc-protected peptide nucleic acids (PNA) monomers containing 5
      aryl- and 5-alkynyl-uracil bases have been synthesized using different palladium
      catalyzed cross-coupling reactions. Starting from the base-unprotected 5-iodo
      uracil PNA monomer, only the Stille couplings were accomplished successfully,
      while Suzuki couplings with boronic acids containing the same aryl groups failed.
      During Sonogashira couplings with terminal alkynes, significant amounts of
      unrequired furano[2,3-d]pyrimidine by-products were formed. Protection of the
      lactam function by p-methoxybenzylation prevented the opportunity for
      intramolecular cyclization as well as formation of a negative charge on the 4-O
      atom, making it possible to reach almost quantitative yields at Sonogashira
      couplings and acceptable conversions in Suzuki reactions.

PMID- 18066880
TI  - Isonucleosides: design and synthesis of new isomeric nucleosides with antiviral
      potential.
AB  - Isonucleosides discovered in our laboratory have been found to have interesting
      antiviral activity. The design, development of methodology, and stereochemical
      synthesis of new isonucleosides of anti-HCV interest are described. Antiviral
      results are cited.

PMID- 18066881
TI  - Development of an antitumor adenosine analog, 3''-ethynyladenosine.
AB  - 3'-ethynyladenosine (EAdo) was an adenosine analog with potent antitumor activity
      against various human tumor cells in vitro. However, EAdo was enzymatically
      inactivated by adenosine deaminase (ADA) in vitro and in vivo. Therefore, we
      synthesized two ADA-resistant EAdo derivatives (2-F-EAdo and EAdo-5'
      monophosphate, EAMP) and examined their antitumor activities.

PMID- 18066882
TI  - 7,5'-O-dibenzylinosines: synthesis and studies on their conformational
      properties.
AB  - Reaction of 2',3'-O-isopropylidene inosine with benzyl bromide (1 h, rt) led to
      the 1,5'-O-dibenzylderivative 4, but by increasing the reaction time or the
      temperature, compound 4 is further transformed into the 1,7,5'-O-tribenzylinosine
      derivative 5. Similarly, the 7-methyl-1,5'-O-dibenzylderivative 6 has been
      synthesized from 4. The 1H-NMR spectra of 5 and 6 showed peculiar chemical shifts
      for geminal protons (H5' and H5'' of the ribose, and the CH2 of the benzyl
      groups). Preliminary NMR studies have been performed, including NOESY experiments
      that point toward the predominant existence of conformers that are stabilized by
      an electrostatic interaction between the positively charged imidazole of the base
      moiety and the high electron density of the 5'-benzyl substituent.

PMID- 18066883
TI  - Transformation of D-(-)-ribose into a natural product-like scaffold via a Lewis
      acid catalyzed intramolecular hetero-Diels-Alder reaction.
AB  - Starting from D-(-)-ribose, a tricyclic natural product-like scaffold suitable
      for combinatorial derivatization was synthesized via an intramolecular hetero
      Diels-Alder reaction. Lithium perchlorate was found to enhance the reaction rate
      and, at the same time, had a pronounced influence on the chemoselectivity of the
      reaction. The stereochemical course of the reaction, however, was not influenced
      by the Lewis acid.

PMID- 18066884
TI  - Synthesis of DNA-oligonucleotides damaged by arylamine-modified 2'
      deoxyguanosine.
AB  - C8-Arylamine-dG adducts bearing a labile N-formamidine group at the exocyclic
      amino function were converted into their corresponding 5'-O-DMTr-3'-O
      phosphoramidite-C8-arylamine-dG derivatives. These compounds were used for the
      automated synthesis of site-specifically modified oligonucleotides. These
      oligonucleotides were characterized by ESI-MS and enzymatic digestion and studied
      for their CD properties and Tm values.

PMID- 18066885
TI  - Synthesis of 3'- S-phosphorothiolate oligonucleotides for their potential use in
      RNA interference.
AB  - The potency of RNA interference (RNAi) undoubtedly can be improved through
      chemical modifications to the small interfering RNAs (siRNA). By incorporation of
      the 3'-S-phosphorothiolate modification into strands of RNA, it is hoped that
      specific regions of a siRNA duplex can be stabilised to enhance the target
      binding affinity of a selected antisense strand into the activated RNA-induced
      silencing complex (RISC*). Oligonucleotides composed entirely of this
      modification are desirable so unconventional 5' --> 3' synthesis is investigated,
      with initial solution-phase testing proving successful. The phosphoroamidite
      monomer required for solid-phase synthesis has also been produced.

PMID- 18066886
TI  - Synthesis and antitumor activity of fluorocyclopentenyl-pyrimidines.
AB  - Synthesis of fluorocyclopentenyl pyrimidine nucleosides 6-9 was enantiopurely
      accomplished employing oxidative rearrangement, RCM reaction and electrophilic
      fluorination starting from d-ribose. Cytosine analog 8 was found to exhibit
      significant anticancer activity in various human tumor cell lines.

PMID- 18066887
TI  - Synthesis of N6-substituted 3'-ureidoadenosine derivatives as highly potent
      agonists at the mutant A3 adenosine receptor.
AB  - Several N6-substituted 3 '-ureidoadenosine derivatives were efficiently
      synthesized starting from D-glucose for the development of H272E mutant A3
      adenosine receptor (AR) agonists. Among compounds tested, 3 '-ureido-N6-(3
      iodobenzyl)adenosine (2c) exhibited the highest binding affinity (Ki = 0.22 micro
      M) at the H272E mutant A3 AR without binding to the natural A3AR.

PMID- 18066888
TI  - Asymmetric synthesis of novel apio carbocyclic nucleoside analogues as potential
      antiviral and antitumor agent.
AB  - Novel apio carbocyclic nucleosides 18-21 were asymmetrically synthesized as
      potential antiviral and antitumor agent, starting from D-ribose employing aldol
      reaction, RCM reaction and Mitsunobu reaction as key reactions.

PMID- 18066889
TI  - Synthesis and anti-HCV activity Of 2''-beta-hydroxymethylated nucleosides.
AB  - Synthesis of 2' -beta-hydroxymethyl nucleosides 3-6 was accomplished, using
      stereoselective hydroxymethylation as a key step. Adenine nucleoside 3 showed
      potent anti-HCV activity, implying that 2' -beta-hydroxymethyl group has the
      appropriate electronic properties interfering with HCV polymerase.

PMID- 18066890
TI  - Stereoselective synthesis of homo-apioneplanocin A as potential inhibitor of S
      adenosylhomocysteine hydrolase.
AB  - Homo-apioneplanocin A (1) as a potential inhibitor of S-adenosylhomocysteine
      hydrolase was synthesized from D-ribose, employing stereoselective
      hydroxymethylation, regioselective oxidation, and regio- and chemoselective
      hydroboration as key steps.

PMID- 18066891
TI  - Synthesis of novel 4'-modified neplanocin A analogues and their inhibitory
      activity against S-adenosyl-L-l-homocysteine hydrolase.
AB  - A new approach was developed for the synthesis of 4'-modified neplanocin A
      analogues, as potential inhibitors against S-adenosyl-L-homocysteine hydrolase.
      The vinylstannane 13, a key intermediate in the present approach, was prepared by
      radical-mediated sulfur-extrusive stannylation.

PMID- 18066892
TI  - 7-deaza-2'-deoxyxanthosine: nucleobase protection and base pairing of
      oligonucleotides.
AB  - Oligonucleotides containing 7-deaza-2'-deoxyxanthosine (1) and 2'-deoxyxanthosine
      (2) were prepared. The 2-(4-nitrophenyl)ethyl group is applicable for 7
      deazaxanthine protection that is removed with DBU by beta-elimination, while the
      deprotection of the allyl residue with Pd (0) catalyst failed. Contrarily, the
      allyl group was found to be an excellent protecting group for 2'-deoxyxanthosine
      (2). The base pairing of nucleosides 1 and 2 with the four canonical DNA
      constituents as well as with 3 within the 12-mer duplexes is studied.

PMID- 18066893
TI  - In search of new inhibitors of HIV-1 replication: synthesis and study of 1-(2'
      Deoxy-beta-D-Ribofuranosyl)-1,2,4-triazole-3-carboxamide as a selective viral
      mutagenic agent.
AB  - With the emergence of HIV strains resistant or cross-resistant to nearly all
      antiretroviral regimen, novel therapy approaches have to be considered. As a part
      of our current work on viral mutagenic compounds, we prepared 1-(2' -deoxy-beta-D
      ribofuranosyl)-1,2,4-triazole-3-carboxamide (2' -deoxy-ribavirin) and its 5' 
      triphosphate derivative. The nucleoside mutagenic activity was evaluated on HIV-1
      NL4-3 in CEMx174 cell culture. After 2.5 months, no reduction on HIV-1 viability
      was observed. On the other hand, in vitro experiments with purified HIV-1 RT
      demonstrated that the triphosphate analog can be incorporated opposite to several
      natural nucleosides.

PMID- 18066894
TI  - Comparative studies of tricyclo-DNA- and LNA-containing oligonucleotides as
      inhibitors of HIV-1 gene expression.
AB  - Trans-activation of HIV-1 transcription is triggered by the interaction of the
      protein Tat and host cellular factors with a 59-residue stem-loop RNA known as
      the trans-activation responsive element (TAR). Here we compare the trans
      activation steric block inhibitory activity of 16-mer oligonucleotides targeted
      to TAR containing tricyclo-DNAs, and their mixmers with LNA or OMe residues, with
      LNA/OMe oligonucleotide. Despite generally weaker TAR RNA binding affinity, all
      tricyclo-DNA oligonucleotides showed similarly good activity levels to OMe/LNA
      oligonucleotide in a HeLa Tat-dependent trans-activation cell reporter assay with
      cationic lipid delivery, but mixmers of tricyclo-DNA were inactive. Tricyclo-DNA
      16-mer showed sequence-specific inhibition of beta-galactosidase expression in an
      anti-HIV HeLa cell reporter assay.

PMID- 18066895
TI  - Perylene diimide-oligonucleotide conjugates constructed by click chemistry.
AB  - Oligonucleotide conjugates were prepared by copper-catalyzed cycloaddition of
      acetylene-modified oligonucleotides to diazido derivative of perylene 3,4,9,10
      tetracarboxylic acid diimide.

PMID- 18066896
TI  - pH-dependent assembly of DNA-gold nanoparticles based on the i-motif.
AB  - Oligonucleotides containing stretches of 2 '-deoxycytidine residues were
      immobilized on 15 nm gold nanoparticles. Under acidic pH conditions a reversible
      supramolecular assembly is formed, induced by the formation of the tetrameric i
      motif structure. The replacement of 2 '-deoxycytidine by 5-propynyl-2 '
      deoxycytidine (dC*) leads to novel i-motif structures. Oligonucleotides
      incorporating multiple residues of dC* were immobilized on 15 nm gold
      nanoparticles and are able to aggregate into i-motif structures even at non
      optimal pH values.

PMID- 18066897
TI  - Thermodynamic analysis of quadruplex DNA-drug interaction.
AB  - This work studies the binding properties of distamycin and its carbamoyl analog,
      containing four pyrrole units, with the [d(TGGGGT)](4) quadruplex by means of
      isothermal titration calorimetry (ITC). Analysis of the ITC data reveals that
      drug/quadruplex binding stoichiometry is 1:1 for both interactions and that
      distamycin analog gives approximately a 10-fold increase in the quadruplex
      affinity.

PMID- 18066898
TI  - 5-arylethynyl-2'-deoxyuridines: energy transfer and SNP-detection.
AB  - Energy transfer between different fluorescent 5-alkynyl-2' -deoxyuridines in
      complementary and mismatched duplexes was studied.

PMID- 18066899
TI  - Some novel adenosine mimics: synthesis and anticancer potential against cervical
      cancer caused by human papilloma virus.
AB  - Two novel adenosine analogs, viz. 9-(1'-beta-D-arabinofuranosyl)-6-nitro-1,3
      dideazapurine or Ara-NDDP (1) and 9-(5'-deoxy-5'-S-(propionic acid) (1'-beta-D
      ribofuranosyl) adenine or SAH analog (2), indigenously synthesized, have been
      found to be potential anticancer agents against cervical cancer caused by human
      papilloma virus.

PMID- 18066900
TI  - Study of different copper (I) catalysts for the "click chemistry" approach to
      carbanucleosides.
AB  - We compare herein the scope of three copper (I) catalysts on the synthesis of
      various 1,4-disubstitued-1,2,3-triazolo-carbanucleosides through a microwave (and
      thermic) assisted Huisgen 1,3-dipolar cycloaddition. The
      tetrakis(acetonitrile)copper hexafluorophosphate ([Cu(CH3CN)4]PF6), the
      imidazoline(mesythyl)copper bromide (Imes)CuBr, and the copper/copper sulfate
      Cu(0)/CuSO4 (II) mixture have been chosen for this study. Their influence in a
      catalytic amount will be analyzed according to the substituent of the alkyne, the
      solvent, or the heating method.

PMID- 18066901
TI  - Synthesis and properties of oligonucleotides containing a cholesterol thymidine
      monomer.
AB  - Highly selective base-pair recognition makes DNA a suitable building block for
      orderly self-assembled structures. For some applications in nanotechnology DNA
      complexes need to be fixed onto surfaces. To fulfil this requirement on lipid
      membranes we have synthesised a thymidine monomer modified with a cholesterol
      moiety. Solution studies show that the melting temperature (Tm) of the duplex,
      with adjacent cholesterols on each strand, is much higher than that of the
      unmodified duplex.

PMID- 18066902
TI  - Preparation of 2'-hydrazino oligonucleotides and their reaction with aldehydes
      and 1,3-diketones.
AB  - Oligodeoxyribonucleotides that contain a hydrazino nucleoside, 2'-O-(2
      hydrazinoethyl)uridine were prepared and shown to react with aldehydes or 1,3
      diketones with the formation of hydrazones or pyrazoles, respectively. The method
      may be applicable for the preparation of oligonucleotide-peptide conjugates.

PMID- 18066903
TI  - Development of the novel drug releasing system triggered by hybridization with
      target sequence.
AB  - We have already established the strategy of synchronous activation by
      hybridization, in which the highly reactive cross-linking agent, 2-amino-6
      vinylpurine nucleoside analog, can be generated from its stable precursors, the
      phenylsulfide derivatives, by a hybridization-promoted activation process with
      selectivity to cytosine. In this study, this in situ activation system was
      applied to the method for the drug releasing system triggered by hybridization
      with the target sequence.

PMID- 18066904
TI  - Lack of interferon (IFN) response to T7 Transcribed pppG (n)(n = 2,3)-shRNA.
AB  - RNA interference (RNAi) mediated by siRNAs has proved to be a highly effective
      gene silencing mechanism with great potential for gene therapeutic applications.
      However, siRNA agents have been shown to exert non-target-related biological
      effects and toxicities, including immune stimulation. Specifically, siRNA
      synthesized from a T7 RNA polymerase system can trigger the potent induction of
      type I IFN in a variety of cells. The single-stranded RNA can also stimulate
      innate cytokine responses in mammals. We found that pppGn (n = 1-3), associated
      with the 5' end of the shRNA produced from the T7 RNA polymerase system, did not
      induce detectable levels of IFN. The residual amount of G associated with the 5'
      end of the transcript was proportional to the reduction of the interferon
      response. We describe a T7 pppGn (n = 1-3) shRNA synthesis system that alleviates
      the IFN response, which will facilitate the design of siRNAs while maintaining
      their full efficacy.

PMID- 18066905
TI  - Reagents for the selective immobilization of oligonucleotides on solid supports.
AB  - New reagents (CPGs and phosphoramidites) for automatic solid phase synthesis of
      modified oligonucleotides were designed. Three oligonucleotides carrying
      fluorescent label at the 5'-terminus and an anchor group at the 3'-terminus were
      prepared and their immobilization in orthogonal conditions on solid supports was
      studied.

PMID- 18066906
TI  - Suppression of hepatitis C virus core protein by short hairpin RNA expression
      vectors in the core protein expression Huh-7 cells.
AB  - Short hairpin RNAs (shRNAs) efficiently inhibit gene expression by RNA
      interference. Here, we report the efficient inhibition by DNA-based vector
      derived shRNAs of core protein expression in Huh-7 cells. The shRNAs were
      designed to target the core region of the hepatitis C virus (HCV) genome. The
      core region is the most conserved region in the HCV genome, making it an ideal
      target for shRNAs. We identified an effective site on the core region for
      suppression of the HCV core protein. The HCV core protein in core protein
      expressing Huh-7 cells was downregulated by core protein-shRNA expression vectors
      (core-shRNA-452, 479, and 503). Our results support the feasibility of using
      shRNA-based gene therapy to inhibit HCV core protein production.

PMID- 18066907
TI  - Novel method for the synthesis of 2' -phosphorylated oligonucleotides.
AB  - We have developed a new method for the preparation of oligodeoxyribonucleotides
      and oligo(2'-O-methylribonucleotides) that contain a 2'-phosphorylated
      ribonucleoside residue, and optimized it to avoid 2' -3' -isomerization and chain
      cleavage. Structures of the 2' -phosphorylated oligonucleotides were confirmed by
      MALDI-TOF MS and enzymatic digestion, and the stability of their duplexes with
      DNA and RNA was investigated. 2'-Phosphorylated oligonucleotides may be useful
      intermediates for the introduction of various chemical groups for a wide range of
      applications.

PMID- 18066908
TI  - Intracellular trapping of cycloSal-pronucleotides by enzymatic cleavage.
AB  - A new synthesis for cycloSal-pronucleotides bearing enzymatically cleavable
      triggers is presented. This trigger is introduced to trap the pronucleotide
      inside cells. The general concept and hydrolysis data in different media are
      discussed.

PMID- 18066909
TI  - New cycloAmb-nucleoside phosphonate prodrugs.
AB  - cycloSal- and cycloAmb-nucleoside phosphonate prodrugs of PMEA were synthesized
      and characterized. Each of these compounds showed different disadvantages in
      hydrolysis. Thus, a new series of cycloAminobenzyl(cycloAmb)-PMEA prodrugs was
      synthezised and studied with regard to their hydrolysis properties and biological
      activity.

PMID- 18066910
TI  - An alternative synthetic method for 4'-C-ethynylstavudine by means of
      nucleophilic substitution of 4'-benzoyloxythymine nucleoside.
AB  - For the synthesis of 2',3' -didehydro-3' -deoxy-4' -C-ethynylthymidine (8: 4' 
      Ed4T), a recently reported promising anti-HIV agent, a new approach was
      developed. Since treatment of 1-(2,5-dideoxy-beta-l-glycero-pent-4
      enofuranosyl)thymine with Pb(OBz)4 allowed the introduction of a 4'-benzoyloxy
      leaving group, nucleophilic substitution at the 4' -position became feasible for
      the first time. Thus, reaction between the 4'-benzoyloxy derivative (11) and
      Me3SiC identical with CAl(Et)Cl as a nucleophile led to the isolation of the
      desired 4'-"down"-ethynyl derivative (15) stereoselectively in 62% yield.

PMID- 18066911
TI  - Fluorescence studies of calf spleen purine nucleoside phosphorylase (PNP)
      complexes with guanine and 9-deazaguanine.
AB  - Interactions of trimeric calf spleen purine nucleoside phosphorylase (PNP) with
      guanine (Gua) and its analogue, 9-deazaguanine (9-deaza-Gua), were studied by
      means of the steady-state fluorescence. The aim was to test the hypothesis that
      the enzyme stabilizes the anionic form of purine, inferred previously from the
      unusual increase of fluorescence observed after binding of guanine by calf spleen
      PNP. We have found that the dissociation constants obtained form titration
      experiments are in fact pH-independent in the range 7.0-10.25 for both PNP/Gua
      and PNP/9-deaza-Gua complexes. In particular, at pH 7.0 we found Kd = 0.12 +/-
      0.02 micro M for Gua and 0.16 +/- 0.01 micro M for 9-deaza-Gua, while at the
      conditions where there is more than 40% of the anionic form the respective values
      were Kd = 0.15 +/- 0.01 micro M for Gua (pH 9.0) and 0.25 +/- 0.02 micro M for 9
      deaza-Gua (pH 10.25). Hence, the enzyme does not prefer binding of anionic forms
      of these ligands in respect to the neutral ones. This result questions the
      involvement of the anionic forms in the reaction catalyzed by trimeric PNPs, and
      contradicts the hypothesis of a strong hydrogen bond formation between the enzyme
      Asn 243 residue and the purine N7 position.

PMID- 18066912
TI  - Interactions of calf spleen purine nucleoside phosphorylase with formycin B and
      its aglycone - spectroscopic and kinetic studies.
AB  - Phosphorolysis of 7-methylguanosine by calf spleen purine nucleoside
      phosphorylase (PNP) is weakly inhibited, uncompetitively, by Formycin B (FB) with
      Ki = 100 micro M and more effectively by its aglycone (7KPP), IC50 35-100 micro
      M. In striking contrast, 7KPP inhibits the reverse reaction (synthesis of 8
      azaguanosine from 8-azaguanine) competitively, with Ki approximately 2-4 micro M.
      Formycin B forms only a weakly fluorescent complex with PNP, and 7KPP even less
      so, indicating that both ligands bind as the neutral, not anionic, forms. 7KPP is
      a rare example of a PNP non-substrate inhibitor of both the phosphorolytic and
      reverse synthetic pathways.

PMID- 18066913
TI  - Cloning, expression, purification, and some properties of calf purine nucleoside
      phosphorylase.
AB  - Calf spleen purine nucleoside phosphorylase (PNP) is considered a model enzyme
      for the trimeric PNPs subfamily. PCR amplification of the calf phosphorylase from
      the calf spleen library, cloning, overexpression of the recombinant PNP, its
      enzymatic activity and interactions with typical ligands of mammalian wild type
      PNP are described. Relative activity of the recombinant phosphorylase versus
      several substrates is similar to the respective values obtained for the enzyme
      isolated from calf spleen. As for the nonrecombinant calf PNP, the unusual
      fluorescence properties of the PNP/guanine complex were observed and
      characterized.

PMID- 18066914
TI  - 5-diacetoxymethyl-cycloSal-d4TMP - A prototype of enzymatically activated
      cycloSal-pronucleotides.
AB  - A new class of "lock-in"-modified cycloSal-pronucleotides has been synthesized.
      On the example of 5-diacetoxymethyl-cycloSal-d4T-monophosphate (5-di-AM-cycloSal
      d4TMP), the concept of enzymatically activated cycloSal-pronucleotides is
      elucidated. Synthesis, hydrolysis studies, and antiviral activities against HIV
      are presented.

PMID- 18066915
TI  - RNAi activity of siRNAs modified with 2'-aminoalkyl-substituted fluorinated
      nucleobases.
AB  - We recently reported that a 1'-deoxy-1'-(4,6-difluoro-1H-benzimidazol-1-yl)-2'
      (beta-aminoethyl)-beta-d-ribofuranose nucleoside appears to be a universal
      nucleoside which does not differentiate between the four natural nucleosides A,
      C, G, and U in duplexes. Moreover, ribozymes modified with this nucleoside analog
      showed a better or at least equal catalytic activity relative to Watson-Crick
      mismatches.[1] Due to these data, we investigated the ability of this compound to
      tolerate Watson-Crick mismatches in order to avoid HIV escape mutations in RNA
      interference. The influence of this nucleoside analog on siRNA efficiency was
      analyzed with a proven siRNA targeting GFP.

PMID- 18066916
TI  - The role of message framing in promoting MMR vaccination: evidence of a loss
      frame advantage.
AB  - This study examined the effects of message framing on intentions to obtain the
      measles, mumps and rubella (MMR) vaccine for one's child and investigated whether
      Theory of Planned Behaviour (TPB) and perceived outcome efficacy variables
      mediate and/or moderate message framing effects. One hundred and forty women read
      either a loss-framed or gain-framed message and then completed measures assessing
      their intentions to obtain the MMR vaccine for their child, and TPB and outcome
      efficacy variables. Exposure to the loss frame increased intentions to obtain the
      MMR vaccine and influenced perceptions of outcome efficacy. This suggests that
      outcome efficacy, but not other TPB variables may mediate framing effects within
      the context of MMR vaccination. Message frame, in addition to TPB variables,
      significantly predicted unique variance in behavioural intentions. These findings
      are discussed within the context of Prospect Theory, perceived risk and
      prevention/detection behaviours.

PMID- 18066917
TI  - Body satisfaction, eating disorders and suicide ideation in an Internet sample of
      self-harmers reporting and not reporting childhood sexual abuse.
AB  - This study examined differences between self-harmers who had and who had not been
      sexually abused in childhood with regards to other risk factors and associated
      behaviours commonly identified in the research literature as being related to
      self-harm. Participants (N = 113, mean age = 19.92 years) were recruited via self
      harm Internet discussion groups and message boards, and completed a web
      questionnaire assessing measures of body satisfaction, eating disorders,
      childhood trauma and suicide ideation. Self-harmers who reported a history of
      childhood sexual abuse scored higher on measures of body dissatisfaction, eating
      disorders, suicide ideation, physical abuse, physical neglect, emotional abuse
      and emotional neglect. These findings implicate sexual abuse as a powerful
      traumatic event that can have severe repercussions on an individual, not only in
      terms of self-harming behaviour but also in terms of developing a wide range of
      maladaptive behaviours in conjunction with self-harm.

PMID- 18066919
TI  - Discussion of posthumous organ donation in Chinese families.
AB  - Since family permission is necessary for organ procurement to occur in China,
      family discussions about posthumous organ donation are crucial for increasing the
      actual organ donation and transplant rate. However, this study found that among
      298 Chinese young adults, most of them (88%) were reluctant to talk about organ
      donation with their families. Based on the Theory of Reasoned Action, this study
      investigated communication within families about organ donation. Psychological
      factors included intention, attitude, subjective norm, death anxiety, and
      knowledge. As expected, the subjective norm was more powerful than attitude in
      explaining family discussions among Chinese people. Death anxiety, but not
      misconception, also significantly lowered the likelihood of family discussion. It
      is concluded that future campaigns for lessening death anxiety and promoting the
      social norm for organ donation must be conducted in Chinese societies, in order
      to encourage family discussions and improve the donation rate.

PMID- 18066918
TI  - Experience of pregnancy and delivery as predictors of postpartum depression.
AB  - This research examined experiences of pregnancy and delivery as predictors of
      three subscales identified within the Edinburgh Postnatal Depression Scale
      (nonspecific depression, anhedonia, and anxiety). Mothers of babies under 1 year
      (N = 415) completed the Edinburgh Postnatal Depression Scale (EPDS) and gave
      information as to number of pregnancies, number of children, and their ratings of
      the difficulty of the course of pregnancy and delivery. Number of pregnancies and
      number of children did not predict scores on any of these subscales. Difficulty
      in the course of pregnancy was a significant positive predictor of nonspecific
      depression, and difficulty of delivery was a significant positive predictor of
      anxiety. Neither of these variables significantly predicted anhedonia. These
      results provide evidence of the heterogeneity of postpartum depression,
      indicating that risk factors differentially influence subscales of the EPDS.

PMID- 18066920
TI  - What do people think about when answering questionnaires to assess unrealistic
      optimism about skin cancer? A think aloud study.
AB  - There is little information concerning what people think about when completing
      questionnaires that assess perceptions of risk, and even less for questionnaires
      assessing unrealistic optimism. The thoughts of 40 participants who displayed
      unrealistic optimism about risks of skin cancer were elicited using think aloud
      methods, when completing both direct and indirect ratings of unrealistic
      optimism. The most common thoughts overall concerned exposure to the sun, and
      features such as skin colouring. Thoughts concerning prevalence, reasons for
      risky behaviour and admissions of ignorance were more common for indirect
      measures of unrealistic optimism than for direct measures. The direct unrealistic
      optimism measures yielded more optimistic ratings for those participants who did
      not mention symptoms or signs of skin damage, and those who mentioned thoughts
      about prevalence. Participants seem to be drawing upon different sources of
      information when completing superficially similar direct and indirect measures of
      unrealistic optimism, which may explain why these measures are usually only
      modestly associated. People do not seem to think about numerical probabilities
      when estimating risk, but instead appear to focus on issues such as exposure to
      risk, and concrete bodily symptoms and signs. This may at least partially explain
      why attempts to influence behaviour by providing probabilistic information are
      generally unsuccessful.

PMID- 18066921
TI  - A reaction-time study of social, health, and personal attributions in relation to
      fluorosed teeth.
AB  - This reaction time study assessed the valence and strength of evaluations of
      people with differing levels of fluorosed teeth. Eighty participants rated
      photographs of smiling faces with four levels of digitally manipulated fluorosed
      teeth. Faces were presented on a computer screen for a period of 2000 ms followed
      by a single word descriptor. Participants quickly indicated whether the
      descriptor applied to the preceding face using a response key. Descriptors
      included health, aesthetic, and personal judgments. Logistic and linear
      regressions revealed that participants were significantly more likely to make
      negative judgments involving health, aesthetic, and person attributions about
      faces with high levels of fluorosis, and to make negative judgments more quickly
      and positive judgments more slowly than those with lower levels of fluorosis.
      These data are consistent with the view that people use negative, easily
      accessible, stereotypes of individuals presenting with health problems.

PMID- 18066922
TI  - A qualitative study of men's experience of myocardial infarction.
AB  - The majority of people experiencing myocardial infarction and attending cardiac
      rehabilitation are male and the outcome of rehabilitation is better for men.
      However, there is a lack of qualitative exploration of how men experience
      myocardial infarction and cardiac rehabilitation, which this study aims to
      address. Ten men who had recently had a myocardial infarction were interviewed
      using a semi-structured format, which covered events around the infarction, its
      impact on various aspects of life, ways of dealing with these experiences and
      experience of cardiac rehabilitation and other medical services. In this paper,
      the themes which emerged from Interpretive Phenomenological Analysis of the
      interview transcripts will be described and discussed in relation to the existing
      literature, and particularly to White et al.'s (in press) study of women who had
      had a myocardial infarction. These themes relate to views of the self, the
      illness and the future, ways of coping and experiences of rehabilitation.
      Implications for services and future research will be discussed.

PMID- 18066923
TI  - Longitudinal study of a school based HIV/AIDS early prevention program for
      Mexican adolescents.
AB  - A quasi-experimental study is reported with four measurement occasions to
      evaluate longer-term effects of a life-skills and HIV/AIDS school-based
      prevention program. Trained teachers administered the program promoting
      precursors of safer sex behavior to 2064 Mexican high-school students at an age
      before most were sexually active. The variables included in the study (knowledge
      about HIV/AIDS prevention, attitudes towards use of condoms, subjective norms,
      intentions to use condoms and life skills as decision-making skills, partner
      communication and individual responsibility) have been reported as precursors of
      protective sexual behavior. The results demonstrate the stability of training
      effects and a positive impact on these precursors over 1 year of follow-up.

PMID- 18066924
TI  - The effect of barrier underestimation on weight management and exercise change.
AB  - Over 60% of all Americans are classified as overweight or obese. This represents
      a major public health concern, as obesity is a risk factor for many other health
      ailments. While many people intend to lose weight, they often have difficulty
      changing their current behavioral patterns (as evidenced by modest correlations
      between intention and behavior). Therefore, one of the major challenges for
      obesity research is to address the gap between intentions to lose weight and
      actual behavior. The current study hypothesized that one reason for the intention
      behavior discrepancy is that people mis-estimate the barriers that they will
      encounter as they follow through with their intentions. Specifically, we
      hypothesized that people underestimate barriers to exercise and diet, and because
      of these underestimations, there is a discrepancy between their intentions and
      behavior. To test these hypotheses, we surveyed faculty and staff at Rutgers
      University (N = 422) at two time points, 1 year apart. The results indicate that
      barriers to dieting behaviors are significantly underestimated and this
      underestimation partially explained the discrepancy between intentions and
      behavior. The results for barriers to exercise behavior were less consistent,
      however. As a whole, these results suggest a possible point of behavioral
      intervention for weight loss.

PMID- 18066925
TI  - Validity of the Perceived Health Competence Scale in a UK primary care setting.
AB  - The Perceived Health Competence Scale (PHCS) is a measure of self-efficacy
      regarding general health-related behaviour. This brief paper examines the
      psychometric properties of the PHCS in a UK context. Questionnaires containing
      the PHCS, the SF-36 and questions about perceived health needs were posted to 486
      patients randomly selected from a GP practice list. Complete questionnaires were
      returned by 320 patients. Analyses of these responses provide strong evidence for
      the validity of the PHCS in this setting. Consequently, we conclude that the PHCS
      is a useful addition to measures of global self-efficacy and measures of self
      efficacy regarding specific behaviours in the toolkit of health psychologists.
      This range of self-efficacy assessment tools will ensure that psychologists can
      match the level of specificity of the measure of expectancy beliefs to the level
      of specificity of the outcome of interest.

PMID- 18066926
TI  - Delimiting species in recent radiations.
AB  - Despite considerable effort from the systematics community, delimiting species
      boundaries in recent radiations remains a daunting challenge. We argue that
      genealogical approaches, although sometimes useful, may not solve this important
      problem, because recently derived species often have not had sufficient time to
      achieve monophyly. Instead, we suggest that population genetic approaches that
      rely on large sets of informative markers like single nucleotide polymorphisms
      (SNPs) provide an alternative framework for delimiting very recently derived
      species. We address two major challenges in applying such markers to species
      delimitation: discovering markers in nonmodel systems and using them to delimit
      recently derived species. Using turtles as a test case, we explore the utility of
      a single, relatively low-coverage genomic resource as an aid in gene and marker
      discovery. We exploit an end-sequenced bacterial artificial chromosome (BAC)
      library from an individual painted turtle (Chrysemys picta) and outline a novel
      protocol that efficiently identifies primer pairs that amplify homologous
      sequences across the tree of living turtles. Preliminary data using this library
      to discover SNPs in Emydura macquarii, a species that diverged from C. picta
      approximately 210 million years ago, indicate that sequences identified from the
      Chrysemys BAC library provide useful SNPs even in this very distantly related
      taxon. Several recent methods in wide use in the population genetics literature
      allow one to discover potential species, or test existing species hypotheses,
      with SNP data and may be particularly informative for very recently derived
      species. As BAC and other genomic resources become increasingly available for
      scattered taxa across the tree of life, we are optimistic that these resources
      will provide abundant, inexpensive markers that will help delimit boundaries in
      problematic, recent species radiations.

PMID- 18066927
TI  - Applications of ecological niche modeling for species delimitation: a review and
      empirical evaluation using day geckos (Phelsuma) from Madagascar.
AB  - Although the systematic utility of ecological niche modeling is generally well
      known (e.g., concerning the recognition and discovery of areas of endemism for
      biogeographic analyses), there has been little discussion of applications
      concerning species delimitation, and to date, no empirical evaluation has been
      conducted. However, ecological niche modeling can provide compelling evidence for
      allopatry between populations, and can also detect divergent ecological niches
      between candidate species. Here we present results for two taxonomically
      problematic groups of Phelsuma day geckos from Madagascar, where we integrate
      ecological niche modeling with mitochondrial DNA and morphological data to
      evaluate species limits. Despite relatively modest levels of genetic and
      morphological divergence, for both species groups we find divergent ecological
      niches between closely related species and parapatric ecological niche models.
      Niche models based on the new species limits provide a better fit to the known
      distribution than models based upon the combined (lumped) species limits. Based
      on these results, we elevate three subspecies of Phelsuma madagascariensis to
      species rank and describe a new species of Phelsuma from the P. dubia species
      group. Our phylogeny continues to support a major endemic radiation of Phelsuma
      in Madagascar, with dispersals to Pemba Island and the Mascarene Islands. We
      conclude that ecological niche modeling offers great potential for species
      delimitation, especially for taxonomic groups exhibiting low vagility and
      localized endemism and for groups with more poorly known distributions. In
      particular, niche modeling should be especially sensitive for detecting recent
      parapatric speciation driven by ecological divergence, when the environmental
      gradients driving speciation are represented within the ecological niche models.

PMID- 18066928
TI  - Adding more ecology into species delimitation: ecological niche models and
      phylogeography help define cryptic species in the black salamander (Aneides
      flavipunctatus).
AB  - Being able to efficiently and accurately delimit species is one of the most basic
      and important aspects of systematics because species are the fundamental unit of
      analysis in biogeography, ecology, and conservation. We present a rationale and
      approach for combining ecological niche modeling, spatially explicit analyses of
      environmental data, and phylogenetics in species delimitation, and we use our
      methodology in an empirical example focusing on Aneides flavipunctatus, the black
      salamander (Caudata: Plethodontidae), in California. We assess the relationships
      between genetic, environmental, and geographic distance among populations. We use
      11 climatic variables and point locality data from public databases to create
      ecological niche models. The suitability of potential contact zones between
      parapatric lineages is also assessed using the data from ecological niche
      modeling. Phylogenetic analyses of portions of the mitochondrial genome reveal
      morphologically cryptic mitochondrial lineages in this species. In addition, we
      find that patterns of genetic divergence are strongly associated with divergence
      in the ecological niche. Our work demonstrates the ease and utility of using
      spatial analyses of environmental data and phylogenetics in species delimitation,
      especially for groups displaying fine-scaled endemism and cryptic species.

PMID- 18066929
TI  - The web and the structure of taxonomy.
AB  - An easily accessible taxonomic knowledge base is critically important for all
      biodiversity-related sciences. At present, taxonomic information is organized and
      regulated by a system of rules and conventions that date back to the introduction
      of binomial nomenclature by Linnaeus. The taxonomy of any particular group of
      organisms comprises the sum information in the taxonomic literature, supported by
      designated type specimens in major collections. In this article, the way modern
      means of disseminating information will change the practice of taxonomy, in
      particular the Internet, is explored. Basic taxonomic information, such as
      specimen-level data, location of types, and name catalogues are already
      available, at least for some groups, on the Web. Specialist taxonomic databases,
      key-construction programs, and other software useful for systematists are also
      increasingly available. There has also been a move towards Web-publishing of
      taxonomic hypotheses, though as yet this is not fully permitted by the Codes of
      Nomenclature. A further and more radical move would be to transfer taxonomy
      completely to the Web. A possible model of this is discussed, as well as a pilot
      project, the "CATE" initiative, which seeks to explore the advantages and
      disadvantages of such a move. It is argued that taxonomy needs to forge better
      links with its user-communities to maintain its funding base, and that an
      important part of this is making the products of its research more accessible
      through the Internet.

PMID- 18066930
TI  - Toward an integrated system of clade names.
AB  - Although the proposition that higher taxa should correspond to clades is widely
      accepted, current nomenclature does not distinguish clearly between different
      clades in nested series. In particular, the same name is often applied to a total
      clade, its crown clade, and clades originating with various nodes, branches, and
      apomorphies in between. An integrated system of clade names is described based on
      categories of clades defined with respect to lineages that have survived to the
      present time. In this system, the most widely known names are applied to crown
      clades, the names of total clades are formed by adding a standard prefix to the
      names of the corresponding crowns, and the names of apomorphy clades describe the
      specific apomorphies with which they originated. Relative to traditional
      approaches, this integrated approach to naming clades is both more precise
      concerning the associations of names with particular clades and more efficient
      with regard to the cognitive effort required to recognize the names of
      corresponding crown and total clades. It also seems preferable to five
      alternatives that could be used to make the same distinctions. The integrated
      system of clade names has several advantages, including the facilitation of
      communication among biologists who study distantly related clades, promoting a
      broader conceptualization of the origins of distinctive clades of extant
      organisms and emphasizing the continuous nature of evolution.

PMID- 18066931
TI  - Increasing the efficiency of searches for the maximum likelihood tree in a
      phylogenetic analysis of up to 150 nucleotide sequences.
AB  - Even when the maximum likelihood (ML) tree is a better estimate of the true
      phylogenetic tree than those produced by other methods, the result of a poor ML
      search may be no better than that of a more thorough search under some faster
      criterion. The ability to find the globally optimal ML tree is therefore
      important. Here, I compare a range of heuristic search strategies (and their
      associated computer programs) in terms of their success at locating the ML tree
      for 20 empirical data sets with 14 to 158 sequences and 411 to 120,762 aligned
      nucleotides. Three distinct topics are discussed: the success of the search
      strategies in relation to certain features of the data, the generation of
      starting trees for the search, and the exploration of multiple islands of trees.
      As a starting tree, there was little difference among the neighbor-joining tree
      based on absolute differences (including the BioNJ tree), the stepwise-addition
      parsimony tree (with or without nearest-neighbor-interchange (NNI) branch
      swapping), and the stepwise-addition ML tree. The latter produced the best ML
      score on average but was orders of magnitude slower than the alternatives. The
      BioNJ tree was second best on average. As search strategies, star decomposition
      and quartet puzzling were the slowest and produced the worst ML scores. The
      DPRml, IQPNNI, MultiPhyl, PhyML, PhyNav, and TreeFinder programs with default
      options produced qualitatively similar results, each locating a single tree that
      tended to be in an NNI suboptimum (rather than the global optimum) when the data
      set had low phylogenetic information. For such data sets, there were multiple
      tree islands with very similar ML scores. The likelihood surface only became
      relatively simple for data sets that contained approximately 500 aligned
      nucleotides for 50 sequences and 3,000 nucleotides for 100 sequences. The RAxML
      and GARLI programs allowed multiple islands to be explored easily, but both
      programs also tended to find NNI suboptima. A newly developed version of the
      likelihood ratchet using PAUP* successfully found the peaks of multiple islands,
      but its speed needs to be improved.

PMID- 18066932
TI  - Naming species in phylogenetic nomenclature.

PMID- 18066935
TI  - Psychiatric comorbidity following traumatic brain injury.
AB  - PRIMARY OBJECTIVE: Survivors of traumatic brain injury (TBI) are at increased
      risk for development of severe, long-term psychiatric disorders. However, the
      aetiology of these disorders remains unclear. This article systematically reviews
      the most current prevalence rates and evidence for causality, in terms of
      established criteria. MAIN OUTCOME AND RESULTS: Psychiatric syndromes are
      consistently present at an elevated rate following TBI. Survivors of TBI are
      particularly susceptible to major depression, generalized anxiety disorder and
      post-traumatic stress disorder. Evidence for a biological gradient is generally
      lacking, although this criterion may not be appropriate in the case of TBI. The
      temporal pattern of onset is variable and reliable critical periods for the post
      injury development of a psychiatric disorder remain to be identified; however,
      individuals appear to remain at risk for years following injury. CONCLUSIONS: Non
      organic factors, including pre-morbid personality traits and post-injury
      psychological reactions to disability and trauma, are implicated in the
      generation and maintenance of post-TBI psychiatric disorder. There remains
      insufficient evidence to conclude what role the neuropathological consequences of
      TBI play in the development of post-TBI psychiatric disorder.

PMID- 18066936
TI  - Suicidality in people surviving a traumatic brain injury: prevalence, risk
      factors and implications for clinical management.
AB  - BACKGROUND: A systematic search was conducted of the literature addressing
      suicidality after traumatic brain injury (TBI). Results from population-based
      studies found that people with TBI have an increased risk of death by suicide (3
      4 times greater than for the general population), as well as significantly higher
      levels of suicide attempts and suicide ideation. Clinical studies have also
      reported high levels of suicide attempts (18%) and clinically significant suicide
      ideation (21-22%) in TBI samples. METHODS AND RESULTS: In reviewing risk factors,
      two prognostic studies using multivariate analysis were identified. Adjusted risk
      statistics from these studies found an elevated risk of suicide for people with
      severe TBI in comparison to concussion (hazard ratio 1.4, 95% CI 1.15-1.75) and
      an elevated risk of suicide attempts among people displaying post-injury suicide
      ideation (adjusted odds ratio 4.9, 95% CI 1.79-13.17) and psychiatric/emotional
      distress (adjusted odds ratio 7.8, 95% CI 2.11-29.04). CONCLUSIONS: To date,
      little evidence exists for the role of pre-morbid psychopathology,
      neuropathology, neuropsychological impairments or post-injury psychosocial
      factors as major risk factors for post-injury suicidality. Finally, there has
      been little empirical examination of approaches to suicide prevention. Therefore,
      current best practice is based on clinical judgement and the untested
      extrapolation of prevention approaches from other clinical populations.

PMID- 18066937
TI  - Brain injury in a forensic psychiatry population.
AB  - OBJECTIVES: The prevalence and profile of adults with a history of traumatic
      brain injury (TBI) has not been studied in large North American forensic mental
      health populations. This study investigated how adults with a documented history
      of TBI differed with the non-TBI forensic population with respect to
      demographics, psychiatric diagnoses and history of offences. METHOD: A
      retrospective chart review of all consecutive admissions to a forensic psychiatry
      programme in Toronto, Canada was conducted. Information on history of TBI,
      psychiatric diagnoses, living environments and types of criminal offences were
      obtained from medical records. RESULTS: History of TBI was ascertained in 23% of
      394 eligible patient records. Compared to those without a documented history of
      TBI, persons with this history were less likely to be diagnosed with
      schizophrenia but more likely to have alcohol/substance abuse disorder. There
      were also differences observed with respect to offence profiles. CONCLUSIONS:
      This study provides evidence to support routine screening for a history of TBI in
      forensic psychiatry.

PMID- 18066938
TI  - The Frontal Systems Behaviour Scale (FrSBe) as a predictor of community
      integration following a traumatic brain injury.
AB  - PRIMARY OBJECTIVE: This study examined the relationships between the Frontal
      Systems Behaviour Scale (FrSBe), neuropsychological tests and community
      integration outcomes among individuals with a history of TBI. METHODS: Seventy
      six individuals with a history of TBI were consecutively recruited from patients
      seen in a Neuropsychology clinic in an academic healthcare setting. Participants
      completed neuropsychological tests, the FrSBe and the Community Integration
      Questionnaire (CIQ) as part of a standard clinical neuropsychological evaluation.
      RESULTS: The FrSBe was a significant predictor of community integration (CIQ)
      outcomes. Specifically, poorer executive functioning (FrSBe Executive
      Functioning) predicted lower CIQ Total Scores, while increased apathy (FrSBe
      Apathy) was associated with reduced CIQ Productivity. Regarding
      neuropsychological tests, only Delayed Memory remained as a predictor: higher
      scores were associated with enhanced CIQ Total Scores and CIQ Social Integration.
      Finally, female gender was associated with superior CIQ Total Scores, CIQ Home
      Integration and CIQ Productivity. CONCLUSIONS: While neuropsychological tests of
      executive functioning failed to add predictive power to models of community
      integration following TBI with this sample, the FrSBe, a measure of behavioural
      manifestations of frontal lobe dysfunction, did predict these important
      functional outcomes. This suggests that use of the FrSBe may enhance the
      ecological validity of information gathered during a clinical neuropsychological
      assessment.

PMID- 18066939
TI  - Functional brain injury rehabilitation: survivor experiences reported by families
      and professionals.
AB  - PRIMARY OBJECTIVE: The researchers investigated rehabilitation experiences of
      brain injury (BI) survivors participating in a functional programme. RESEARCH
      DESIGN: The researchers used a phenomenological approach involving the collection
      of artifacts and the analysis of focus group discussions through horizontalizing
      statements, creating meaning units and clustering codes. METHODS AND PROCEDURES:
      Focus groups including staff members and survivors' relatives reported
      perceptions about the programme and survivors' experiences; programme artifacts
      (e.g. survivors' schedules, website information) provided additional information.
      Survivors verified focus group responses and an analysis using five assessment
      measures served to validate positive functional changes among programme
      participants. MAIN OUTCOMES: Three general categories of themes emerged:
      components of functional therapy, programme/culture features supporting
      functional therapy and family members' and survivors' reactions to a functional
      programme. Sub-categories and themes provided details about issues central to
      functional BI treatment. CONCLUSIONS: The findings suggest that functional
      therapy programmes: (a) address family and survivors' goals, (b) occur in the
      community or real world, (c) are implemented by people in survivors'
      environments, (d) are collaborative, (e) focus on a positive culture, (f) build
      on basic skills, (g) allow exploration of discharge options, (h) preserve
      survivors' privacy and dignity and (i) recognize difficulties associated with
      transitioning from acute to post-acute rehabilitation.

PMID- 18066940
TI  - Alcohol and drug use following traumatic brain injury: a prospective study.
AB  - PRIMARY OBJECTIVES: To establish pre-morbid alcohol and drug use in persons with
      TBI, relative to controls, investigate how patterns of substance use change over
      time following TBI and identify factors associated with heavy post-injury
      substance use. METHODS AND PROCEDURES: The Alcohol Use Disorders Identification
      test (AUDIT) and Drug Abuse Screening Test (DAST) was completed by 121 hospital
      inpatients with TBI, documenting pre-injury alcohol and drug use, and 133
      demographically similar controls. Participants with TBI completed these measures
      and the Hospital Anxiety and Depression Scale (HADS) again 1 and 2 years post
      injury and 76 also completed them at 3 years. RESULTS: Participants with TBI
      showed similar levels of drug and alcohol use to controls pre-injury, with 31.4%
      of the TBI group and 29.3% of controls drinking at hazardous levels. Alcohol and
      drug use declined in the first year post-injury, but increased by 2 years post
      injury, with only 21.4% of participants with TBI reporting abstinence from
      alcohol and 25.4% drinking at hazardous levels. Only 9% showed a drug problem,
      but 24% had returned to some drug use. Those showing heavy alcohol use post
      injury were young, male and heavy drinkers pre-injury. Drug and alcohol use was
      similar at 3 years post-injury. CONCLUSIONS: More active intervention is needed
      to reduce alcohol and drug use following TBI.

PMID- 18066941
TI  - PTA testing, the Westmead post traumatic amnesia scale and opiate analgesia: a
      cautionary note.
AB  - OBJECTIVE: To assess the validity of the Westmead PTA scale in patients treated
      with opiate analgesia. METHOD: Seventeen non-head injured, non-traumatic,
      electively hospitalized orthopaedic patients treated with opiate analgesia were
      tested on the Westmead PTA scale for a minimum of 2 consecutive days (n=17) to a
      maximum of 4 consecutive days (n=10). RESULTS: Only 20% of participants tested
      over 4 days reached criteria of three consecutive 12/12 scores on the Westmead
      PTA scale. Daily failure rates on the 12 item scale ranged from 36-70%. All
      failures were on the 'new learning' items, orientation items were never failed.
      CONCLUSIONS: The low pass rate of non-head injured patients treated with opiate
      analgesics indicates that the Westmead PTA scale is non-specific to traumatic
      brain injury and is probably an invalid measure of post-traumatic amnesia in
      patients actively treated with opiates. Implications for the measurement and
      accurate classification of traumatic brain injury patients are discussed.

PMID- 18066942
TI  - Memory outcome at 5 years post-childhood traumatic brain injury.
AB  - PRIMARY OBJECTIVE: This study seeks to extend previous findings by documenting
      memory performance in a sample of 70 children at 5 years post-injury. It was
      anticipated that increasing injury severity would be associated with decreased
      performance on working and complex memory tasks. It was also expected that injury
      severity would significantly predict memory, but that the time from insult to
      subsequent testing would be associated with an increased relationship to non
      injury factors. RESEARCH DESIGN: Participants were assessed at 5 years post
      injury, aged between 6-14 years, using measures of immediate, working and complex
      memory. METHODS AND PROCEDURES: The sample comprised 18 children who had
      sustained a severe TBI, 24 with a moderate TBI, 11 with a mild TBI and 17 healthy
      controls, matched for age, gender and socio-economic-status. RESULTS: Results
      indicated that severe TBI was associated with decreased complex auditory-verbal
      memory performance, although children with TBI did not display impairment on
      immediate, working or complex visual-spatial memory. While injury severity
      significantly predicted complex memory outcome, non-injury factors failed to
      significantly predict either working or complex memory performance. CONCLUSIONS:
      Future research should be engineered towards further clarifying what influences
      recovery from childhood TBI in the elongated post-injury period.

PMID- 18066943
TI  - Prospective evaluation of oro-pharyngeal dysphagia after severe traumatic brain
      injury.
AB  - PRIMARY OBJECTIVE: To evaluate clinical, videofluoroscopic findings and clinical
      evolution of neurogenic dysphagia and to establish the prognostic factors.
      RESEARCH DESIGN: Prospective cohort study. METHODS AND PROCEDURES: Forty-eight
      patients with severe traumatic brain injury (TBI) and clinically-suspected oro
      pharyngeal dysphagia were studied. Clinical evaluation of oro-pharyngeal
      dysphagia and videofluoroscopic examination were performed. Clinical evolution
      was based on feeding mode at discharge, the presence of respiratory complications
      and body mass index (BMI) at admission and at discharge. MAIN OUTCOMES AND
      RESULTS: Sixty-five per cent of patients had impaired gag reflex and 44% cough
      during oral feeding. Videofluoroscopy revealed some type of disorder in 90% of
      cases: 65% in the oral phase and 73% in the pharyngeal phase (aspiration in
      62.5%, being silent in 41%). At discharge, 45% were on normal diet, 27% on a
      modified oral diet, 14% combined oral intake and gastrostomy feeding and 14% were
      fed exclusively by gastrostomy. Feeding mode at discharge substantially
      correlated with RLCF score at admission (p=0.04) and with RLCF (p=0.009) and DRS
      (p=0.02) scores at discharge. CONCLUSIONS: Aspiration is very frequent in
      patients with severe TBI, being silent in almost half. Cognitive function
      evaluated with the RLCF is the best prognostic factor. At discharge, 72% of the
      patients were on oral food intake despite having severe TBI.

PMID- 18066944
TI  - The value of the D-Dimer assay for predicting vein thrombosis in rehabilitation
      patients receiving prophylactic low molecular weight heparin doses.
AB  - PURPOSE: Early diagnosis and treatment of venous thrombosis biocontact="no" are
      essential in preventing pulmonary embolism (PE) and reducing the risk of
      recurrence. The objective was to assess the usefulness of the D-Dimer testing to
      rule out symptomatic VT in populations of patients receiving heparin in
      prophylactic doses. METHODS: One hundred and twenty-three rehabilitation patients
      with medium or high risk for VT were investigated. Patients were affected by
      acquired cerebral diseases (n=31), severe brain damage (n=32) or orthopaedic
      surgical sequelae for major joint replacement or multiple limb fractures (n=60).
      All patients were receiving prophylactic heparin doses. D-Dimer levels were
      assessed using Dimertest Latex Agglutination Assay in citrated plasma. Single
      blinded compression Doppler Ultrasound (DUS) examination was performed in
      conformity with international standards. RESULTS: In this specific setting, good
      sensitivity and specificity of the D-Dimer test was confirmed in patients with
      acquired cerebral diseases during rehabilitation, whereas false positive results
      were found in most patients who had undergone major joint replacement, until
      several weeks after surgery. CONCLUSIONS: In rehabilitation patients receiving
      prophylactic heparin doses, the D-Dimer test seems to confirm high sensitivity
      and high negative predictive value for VT and PE. Relevant clinical variables
      seem to reduce the usefulness of the D-Dimer test as a screening tool for VT, at
      least in orthopaedic patients with joint prosthesis.

PMID- 18066945
TI  - Functional neuroimaging evidence for high cognitive effort on the Word Memory
      Test in the absence of external incentives.
AB  - PRIMARY OBJECTIVE: This study presents data from a functional neuroimaging
      experiment which brings into question whether poor performance on the Word Memory
      Test (WMT) can be construed as straightforward evidence for 'poor effort' in the
      context of cognitive assessment, as asserted in a recent report in this journal.
      METHODS AND PROCEDURES: Functional magnetic resonance image (fMRI) data were
      acquired from four participants without brain injury who engaged in the delayed
      recognition (DR) portion of Green's WMT protocol. OUTCOMES AND RESULTS: Compared
      to a simple perceptual identification control task, this study found a highly
      reliable activation pattern across all participants which was restricted almost
      exclusively to cortical areas most commonly associated with task difficulty,
      memory load, concentration and other forms of cognitive effort These areas
      include dorsolateral prefrontal cortex, anterior insula, superior parietal cortex
      and the dorsal anterior cingulate. CONCLUSIONS: These findings demonstrate that
      the WMT activates numerous cortical regions that are critical for cognitive
      effort. Given the extensive neural network necessary to perform the WMT, this
      study raises important questions about what WMT 'failure' truly means in patients
      with traumatic brain injury, who have increased likelihood of disruption within
      this neural network of vision, language, attention, effort and working memory.

PMID- 18066947
TI  - Towards scarless surgery: an endoscopic ultrasound navigation system for
      transgastric access procedures.
AB  - OBJECTIVE: Scarless surgery is an innovative and promising technique that may
      herald a new era in surgical procedures. We have created a navigation system,
      named IRGUS, for endoscopic and transgastric access interventions and have
      validated it in in vivo pilot studies. Our hypothesis is that endoscopic
      ultrasound procedures will be performed more easily and efficiently if the
      operator is provided with approximately registered 3D and 2D processed CT images
      in real time that correspond to the probe position and ultrasound image.
      MATERIALS AND METHODS: The system provides augmented visual feedback and
      additional contextual information to assist the operator. It establishes
      correspondence between the real-time endoscopic ultrasound image and a
      preoperative CT volume registered using electromagnetic tracking of the
      endoscopic ultrasound probe position. Based on this positional information, the
      CT volume is reformatted in approximately the same coordinate frame as the
      ultrasound image and displayed to the operator. RESULTS: The system reduces the
      mental burden of probe navigation and enhances the operator's ability to
      interpret the ultrasound image. Using an initial rigid body registration, we
      measured the mis-registration error between the ultrasound image and the
      reformatted CT plane to be less than 5 mm, which is sufficient to enable the
      performance of novice users of endoscopic systems to approach that of expert
      users. CONCLUSIONS: Our analysis shows that real-time display of data using rigid
      registration is sufficiently accurate to assist surgeons in performing endoscopic
      abdominal procedures. By using preoperative data to provide context and support
      for image interpretation and real-time imaging for targeting, it appears probable
      that both preoperative and intraoperative data may be used to improve operator
      performance.

PMID- 18066948
TI  - Surgical targeting accuracy analysis of six methods for subthalamic nucleus deep
      brain stimulation.
AB  - A commonly adopted surgical target in deep brain stimulation (DBS) procedures,
      the subthalamic nucleus (STN) is located deep within the brain and is surrounded
      by delicate deep-brain structures. Symptoms of Parkinson's disease can be reduced
      by precisely implanting a multi-electrode stimulator at a specific location
      within the STN and delivering the appropriate signal to the target. A number of
      techniques have recently been proposed to facilitate STN DBS surgical targeting
      and thereby improve the surgical outcome. This paper presents a retrospective
      study evaluating the target localization accuracy and precision of six approaches
      in 55 STN DBS procedures. The targeting procedures were performed using a
      neurosurgical visualization and navigation system, which integrates normalized
      and standardized anatomical and functional information into the planning
      environment. In this study, we employed as the "gold standard" the actual
      surgical target locations determined by an experienced neurosurgeon using both
      pre-operative image-guided surgical target/trajectory planning and intra
      operative electrophysiological exploration and confirmation. The surgical target
      locations determined using each of the six targeting methods were compared with
      the "gold standards". The average displacement between the actual surgical
      targets and those planned with targeting approaches was 3.0 +/- 1.3 mm, 3.0 +/-
      1.3 mm, 3.0 +/- 1.0 mm, 2.6 +/- 1.1 mm, 2.5 +/- 0.9 mm, and 1.7 +/- 0.7 mm for
      approaches based on T2-weighted MRI, a brain atlas, T1 and T2 maps, an
      electrophysiological database, a collection of final surgical targets from
      previous patients, and the combination of these functional and anatomical data,
      respectively. The technique incorporating both anatomical and functional data
      provides the most reliable and accurate target position for STN DBS.

PMID- 18066949
TI  - HMM assessment of quality of movement trajectory in laparoscopic surgery.
AB  - Laparoscopic surgery poses many different constraints for the operating surgeon,
      resulting in a slow uptake of advanced laparoscopic procedures. Traditional
      approaches to the assessment of surgical performance rely on prior classification
      of a cohort of surgeons' technical skills for validation, which may introduce
      subjective bias to the outcome. In this study, Hidden Markov Models (HMMs) are
      used to learn surgical maneuvers from 11 subjects with mixed abilities. By using
      the leave-one-out method, the HMMs are trained without prior clustering of
      subjects into different skill levels, and the output likelihood indicates the
      similarity of a particular subject's motion trajectories to those of the group.
      The results show that after a short period of training, the novices become more
      similar to the group when compared to the initial pre-training assessment. The
      study demonstrates the strength of the proposed method in ranking the quality of
      trajectories of the subjects, highlighting its value in minimizing the subjective
      bias in skills assessment for minimally invasive surgery.

PMID- 18066950
TI  - Super resolution in robotic-assisted minimally invasive surgery.
AB  - In minimally invasive surgery, a small field of view is often required to achieve
      a large magnification factor during micro-scale tasks such as coronary
      anastomosis. However, constantly changing the orientation and focal length of the
      laparoscope camera is cumbersome, and can impose extra visual and cognitive load
      on the operating surgeon in terms of realigning the visual pathways and
      anatomical landmarks. The purpose of this paper is to investigate the use of
      fixational movements in robotic-assisted minimally invasive surgery, such that
      the perceived resolution of the foveal field of view is greater than the
      intrinsic resolution of the laparoscope camera. The proposed technique is based
      on super resolution imaging using projection onto convex sets for monochrome
      images, and a maximum a posteriori method with a novel YIQ space-based prior for
      color images. Validation with both phantom and in vivo data from totally
      endoscopic coronary artery bypass surgery is provided.

PMID- 18066951
TI  - Development of an image-guided robot for small animal research.
AB  - We developed a robot system that can be used for image-guided experimental
      procedures on small animals, where the goal is to perform physical actions at
      specific positions identified on a preoperative image. The animal is first placed
      in a fixture that is compatible with all imaging systems of interest, including
      PET, SPECT, CT and MRI. After imaging, the fixture is attached and registered to
      the robot system, where the image-guided intervention is performed. This system
      has been applied to perform pO(2) measurements with physical probes based on
      tumor hypoxia images obtained in an animal PET scanner. This paper focuses on the
      design and validation of the robot system. The validation is performed using a
      phantom and includes a new method for estimating the Fiducial Localization Error
      (FLE) that is based on the measured Fiducial Distance Error (FDE). The results
      indicate that the robot system can position the measurement probe at a defined
      target with a mean error that is less than 0.4 mm.

PMID- 18066952
TI  - Robotic system for prostate brachytherapy.
AB  - In contemporary brachytherapy procedures, needle placement at the desired target
      is challenging for a variety of reasons. A robot-assisted brachytherapy system
      can potentially improve needle placement and seed delivery, resulting in enhanced
      therapeutic outcome. In this paper we present a robotic system with 16 degrees of
      freedom (DOF) (9 DOF for the positioning module and 7 DOF for the surgery module)
      that has been developed and fabricated for prostate brachytherapy. Strategies to
      reduce needle deflection and target movement were incorporated after extensive
      experimental validation. Provision for needle motion and force feedback was
      included in the system to improve robot control and seed delivery. Preliminary
      experimental results reveal that the prototype system is sufficiently accurate in
      placing brachytherapy needles.

PMID- 18066953
TI  - Role of type 2C protein phosphatases in growth regulation and in cellular stress
      signaling.
AB  - A number of interesting features, phenotypes, and potential clinical applications
      have recently been ascribed to the type 2C family of protein phosphatases. Thus
      far, 16 different PP2C genes have been identified in the human genome, encoding
      (by means of alternative splicing) for at least 22 different isozymes. Virtually
      ever since their discovery, type 2C phosphatases have been predominantly linked
      to cell growth and to cellular stress signaling. Here, we provide an overview of
      the involvement of type 2C phosphatases in these two processes, and we show that
      four of them (PP2Calpha, PP2Cbeta, ILKAP, and PHLPP) can be expected to function
      as tumor suppressor proteins, and one as an oncoprotein (PP2Cdelta /Wip1). In
      addition, we demonstrate that in virtually all cases in which they have been
      linked to the stress response, PP2Cs act as inhibitors of cellular stress
      signaling. Based on the vast amount of experimental evidence obtained thus far,
      it therefore seems justified to conclude that type 2C protein phosphatases are
      important physiological regulators of cell growth and of cellular stress
      signaling.

PMID- 18066954
TI  - Encoding olfactory signals via multiple chemosensory systems.
AB  - Most animals have evolved multiple olfactory systems to detect general odors as
      well as social cues. The sophistication and interaction of these systems permit
      precise detection of food, danger, and mates, all crucial elements for survival.
      In most mammals, the nose contains two well described chemosensory apparatuses
      (the main olfactory epithelium and the vomeronasal organ), each of which
      comprises several subtypes of sensory neurons expressing distinct receptors and
      signal transduction machineries. In many species (e.g., rodents), the nasal
      cavity also includes two spatially segregated clusters of neurons forming the
      septal organ of Masera and the Grueneberg ganglion. Results of recent studies
      suggest that these chemosensory systems perceive diverse but overlapping
      olfactory cues and that some neurons may even detect the pressure changes carried
      by the airflow. This review provides an update on how chemosensory neurons
      transduce chemical (and possibly mechanical) stimuli into electrical signals, and
      what information each system brings into the brain. Future investigation will
      focus on the specific ligands that each system detects with a behavioral context
      and the processing networks that each system involves in the brain. Such studies
      will lead to a better understanding of how the multiple olfactory systems, acting
      in concert, offer a complete representation of the chemical world.

PMID- 18066955
TI  - Glycan antagonists and inhibitors: a fount for drug discovery.
AB  - Glycans, the carbohydrate chains of glycoproteins, proteoglycans, and
      glycolipids, represent a relatively unexploited area for drug development
      compared with other macromolecules. This review describes the major classes of
      glycans synthesized by animal cells, their mode of assembly, and available
      inhibitors for blocking their biosynthesis and function. Many of these agents
      have proven useful for studying the biological activities of glycans in isolated
      cells, during embryological development, and in physiology. Some are being used
      to develop drugs for treating metabolic disorders, cancer, and infection,
      suggesting that glycans are excellent targets for future drug development.

PMID- 18066956
TI  - Intrahepatic cholestasis and eclampsia: a case report.
AB  - Intrahepatic cholestasis of pregnancy is the most common liver disorder in
      pregnancy that adversely affects maternal well being and fetal outcome. We
      present a case of eclampsia that followed intrahepatic cholestasis of pregnancy
      in a patient who has a sister with the same history in her two former pregnancies
      despite being treated with ursodeoxycholic acid. Intrahepatic cholestasis and
      pregnancy is briefly reviewed based on a unique case report presenting with
      intrahepatic cholestasis complicated by eclampsia.

PMID- 18066957
TI  - Women's views of their experiences in the CHIPS (Control of Hypertension in
      Pregnancy Study) Pilot Trial.
AB  - BACKGROUND: Satisfaction with maternity care is strongly related to the patient
      caregiver relationship and involvement in the decision-making process. We sought
      to compare women's views about their care in a randomized trial of 'less tight'
      vs. 'tight' control of non-proteinuric pre-existing or gestational hypertension
      in pregnancy. METHODS: In the CHIPS Pilot Trial, women completed a postpartum
      questionnaire to assess their likes and dislikes about their blood pressure (BP)
      management and trial participation. Comparisons were descriptive. RESULTS:
      Baseline information was similar for the 'less tight' and 'tight' control groups.
      Of 132 women, 126 (95.5%) from 17 centers completed a postpartum questionnaire,
      usually within days of delivery. At least 90% of women in both groups were
      satisfied with their care, and would be willing to participate again or recommend
      participation to a friend. Women in both the 'less tight' and 'tight' groups were
      satisfied with BP management (98.4% vs. 95.1%), and the frequency of tests of
      maternal and fetal well being. Half of women in both groups perceived that their
      BP was too high and that caregivers thought that their BP was too high. More
      women in the 'less tight' (vs. the 'tight') control group took less medication
      than expected (71.7% vs. 38.2%). More women in the 'tight' (vs. the 'less tight')
      group took more medication than they expected (60.0% vs. 22.2%). At least 60% of
      all women used home BP monitoring. CONCLUSION: In the CHIPS Pilot Trial, while
      women stated that they were satisfied with their BP management and care, a
      surprising 50% in both groups thought that their BP was too high. The majority of
      women used home BP monitoring, the role of which must be further defined in
      hypertensive pregnancies.

PMID- 18066958
TI  - Characteristic laboratory changes in pregnancies complicated by HELLP syndrome.
AB  - INTRODUCTION: HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet
      count) is a severe, life-threatening form of preeclampsia. Its development is
      accompanied by significant increase in maternal, as well as fetal, morbidity, and
      mortality rates. It is essential, therefore, for obstetricians to be familiar
      with the disease. MATERIALS AND METHODS: In the past 10 years, 107 patients were
      treated for HELLP syndrome in the intensive care unit (ICU) of the First
      Department of Obstetrics and Gynaecology, Semmelweis University. During this
      time, we studied the characteristic laboratory findings of the disease from the
      day of the diagnosis until the first few postpartum days. RESULTS: HELLP syndrome
      was present in 0.37% of all women having live births. In our study, the liver
      enzymes AST, and LDH, and the level of total bilirubin (indicating the degree of
      hemolysis), and repeated thrombocyte counts were suitable for following the
      cases. The AST, LDH and bilirubin levels returned to normal between the third and
      seventh days postpartum. The platelet count passed the critical level of
      100,000/microL on the third to fourth day. CONCLUSIONS: We have found that the
      platelet count, LDH, AST, and total bilirubin levels proved to be useful
      indicators of the progression of HELLP syndrome.

PMID- 18066959
TI  - Home blood pressure levels in pregnant women with chronic hypertension.
AB  - OBJECTIVE: To explore the difference between office and home blood pressure (BP)
      monitoring in normotensive and hypertensive pregnant women. METHODS: We compared
      the mean of 1 week home BP with office BP, measured by aneroid devices, in 20
      normotensive women (68 BP assessments) and 100 women with mild essential chronic
      hypertension without superimposed gestational hypertension (429 BP assessments).
      Different approaches were used including the Bland-Altman method to investigate
      the discrepancies between office and home BP. RESULTS: Systolic office BP in
      normotensive women (p = 0.004) and diastolic office BP in hypertensive women (p =
      0.001) were lower than home BP. The concordance between office and home BPs was
      better for diastolic BP than for systolic BP. Only a small number of hypertensive
      women presented home BP >or=135/85 mm Hg. CONCLUSIONS: In our study population,
      the concurrence between office and home BPs is good with the exception of
      systolic BP in normotensive women. Home blood pressure measurement criteria used
      in nonpregnant individuals are not adequate in pregnancy.

PMID- 18066960
TI  - Fibrinogen concentration and factor VIII activity in women with preeclampsia.
AB  - OBJECTIVE: To compare fibrinogen concentration and factor VIII activity obtained
      from pregnant women with preeclampsia with those obtained from women with either
      normal pregnancies or with complications unrelated to preeclampsia. MATERIALS AND
      METHODS: Fibrinogen concentration and factor VIII activity were measured in the
      following groups: normal pregnancy, consisting of women at routine 16- to 28-week
      antenatal visits or after admission at term for elective cesarean section; women
      with non-preeclampsia (non-PE) related conditions, including women with
      threatened abortion, cholestasis, systemic lupus erythematosus (SLE), and
      previous deep venous thrombosis (DVT); and women with preeclampsia as defined by
      the Australasion Society for the Study of Hypertension in Pregnancy (ASSHP)
      criteria. Blood was collected from 44 women in each group. Fibrinogen
      concentration and factor VIII activity were measured. RESULTS: Fibrinogen
      concentrations and factor VIII activities were higher in women with preeclampsia
      compared with those from women with either normal or complicated pregnancies (p <
      0.05). It was twice as likely that a woman with preeclampsia would have a raised
      fibrinogen and factor VIII levels. The ranges for each analyte did, however, show
      overlap. Women with preeclampsia were more likely to have both a raised
      fibrinogen concentration and increased factor VIII activity than other pregnant
      women (p < 0.001). CONCLUSION: This study has shown a novel increase in both
      fibrinogen concentration and factor VIII activity in pregnant women with
      preeclampsia compared with values obtained from women with normal or non
      preeclampsia complicated pregnancies, with women with preeclampsia twice as
      likely to have a raised fibrinogen concentration and increased factor VIII
      activity. These changes may contribute to the hypercoagulability seen in
      preeclampsia.

PMID- 18066961
TI  - Hypertriglyceridemia is linked to reduced nitric oxide synthesis in women with
      hypertensive disorders of pregnancy.
AB  - BACKGROUND: Hypertensive disorders of pregnancy (HDP), which affect 8% to 15% of
      pregnancies, are associated with nitric oxide dysfunction and hyperlipidemia, but
      their precise role in HDP remains controversial. In order to gain more insight
      into the mechanisms underlying HDP, we evaluated some indicators common to the
      diseases associated with endothelial dysfunction. METHODS: Plasma samples were
      obtained from 47 normotensive women (control group) and from 27 women with HDP
      (experimental group). All women were 7 months pregnant. Body mass index as well
      as triglycerides, nitrite concentrations, total cholesterol, LDL-cholesterol, HDL
      cholesterol, glucose, and glycated hemoglobin were determined. RESULTS: Our
      results showed significant differences in body mass index (30.4 +/- 1.3 vs 28.3
      +/- 0.6 kg/m(2), p < 0.05), triglycerides (363 +/- 137 vs. 263 +/- 80 mg/dL, p <
      0.01), nitrites (19.6 +/- 5.2 vs. 15.2 +/- 5.0 micromol/L, p < 0.01), and glucose
      (92 +/- 25 vs. 81 +/- 10.8 mg/dL, p < 0.05) in women from the experimental group
      compared with the control group. Interestingly, nitric oxide synthesis was
      significantly reduced when triglycerides and cholesterol concentrations were
      increased (p < 0.018 and p < 0.002, respectively). Moreover, there was a strong
      association (odds ratio, 3.5) between a family history of type 2 diabetes
      mellitus and the development of HDP, especially preeclampsia. CONCLUSIONS: It may
      be useful to screen pregnant women for plasma nitrites and serum triglycerides to
      identify those at risk of developing HDP, especially in women with a family
      history of type 2 diabetes mellitus.

PMID- 18066962
TI  - Relationship between thrombophilic disorders and type of severe early-onset
      hypertensive disorder of pregnancy.
AB  - OBJECTIVE: To determine whether specific subtypes of early-onset hypertensive
      disorders of pregnancy (haemolysis, elevated liver enzymes, low platelets [HELLP]
      syndrome; severe preeclampsia; eclampsia; and fetal growth restriction) differ in
      increased prevalences of thrombophilic disorders. DESIGN: Cohort study. SETTING:
      Two university hospitals in Amsterdam, the Netherlands. POPULATION: 216 patients
      participating in a randomized clinical trial with severe and early-onset
      hypertensive disorders of pregnancy. METHODS: More than 3 months after delivery,
      all patients were invited for a thrombophilia screening protocol, including
      hereditary thrombophilic disorders (Factor II or V-Leiden mutation, APC
      resistance, protein S deficiency), antiphospholipid antibodies (anticardiolipin
      antibodies and lupus anticoagulant activity), and hyperhomocysteinemia (before
      and after methionin challenge). Disease expression was classified by HELLP
      syndrome, severe preeclampsia, or neonatal birth weight ratio below the median
      (0.65). Univariate and multinomial regression analyses examined the association
      of disease expression with thrombophilic disorders, and other associated factors
      (chronic hypertension, smoking, body mass index, positive family history of
      cardiovascular morbidity, and demographic parameters). MAIN OUTCOME MEASURES:
      incidence of thrombophilic disorders in different subtypes of disease. RESULTS:
      Overall prevalence of thrombophilic disorders in 206 (95%) screened women was
      36%. Chronic hypertension was present in 32%, and 34% had a positive family
      history of cardiovascular morbidity. Multinomial regression analysis showed that
      hereditary thrombophilia was more frequent among women with infants with a birth
      weight ratio <0.65 than in women with HELLP syndrome or severe preeclampsia (p =
      0.01, OR 5.1 (1.5 to 7.3) and OR 3.4 (1.1 to 10.6), respectively). High body mass
      index was less frequent in women with HELLP syndrome than in those with severe
      preeclampsia or fetal growth restriction (p = 0.06, OR 0.5 (0.3 to 0.9) and OR
      0.4 (0.2 to 1.0), respectively). CONCLUSION: In this population, the high
      prevalence of thrombophilic factors and chronic hypertension was confirmed. There
      were small differences between groups. Hereditary thrombophilic disorders were
      associated with fetal growth restriction but not with type of maternal disease,
      suggesting an effect on placental function. Maternal body mass index was lower in
      women with HELLP syndrome.

PMID- 18066963
TI  - Current CHS and NHBPEP criteria for severe preeclampsia do not uniformly predict
      adverse maternal or perinatal outcomes.
AB  - OBJECTIVE: To determine the association between adverse maternal/perinatal
      outcomes and Canadian and U.S. preeclampsia severity criteria. METHODS: Using
      PIERS data (Preeclampsia Integrated Estimate of RiSk), an international
      continuous quality improvement project for women hospitalized with preeclampsia,
      we examined the association between preeclampsia severity criteria and adverse
      maternal and perinatal outcomes (univariable analysis, Fisher's exact test). Not
      evaluated were variables performed in <80% of pregnancies (e.g., 24-hour
      proteinuria). RESULTS: Few of the evaluated variables were associated with
      adverse maternal (chest pain/dyspnea, thrombocytopenia, 'elevated liver enzymes',
      HELLP syndrome, and creatinine >110 microM) or perinatal outcomes (dBP >110 mm Hg
      and suspected abruption) (at p < 0.01). CONCLUSIONS: In the PIERS cohort, most
      factors used in the Canadian or American classifications of severe preeclampsia
      do not predict adverse maternal and/or perinatal outcomes. Future classification
      systems should take this into account.

PMID- 18066964
TI  - Perinatal changes of circulating N-terminal pro B-type natriuretic peptide (NT
      proBNP) in normal and intrauterine-growth-restricted pregnancies.
AB  - OBJECTIVE: To investigate changes in NT-proBNP in intrauterine-growth-restricted
      (IUGR) and appropriate-for-gestational-age (AGA) pregnancies. METHODS: NT-proBNP
      levels were measured in 40 mothers (MS), umbilical cords (UC), and their 20 IUGR/
      20 AGA neonates on day 1 (N1) and day 4 (N4). RESULTS: UC, N1, and N4 NT-proBNP
      was lower in IUGR pregnancies (p <or= 0.049). In both groups, NT-proBNP levels
      were similar in MS and higher in N1 (p <or= 0.001). In AGA, MS NT-proBNP
      correlated positively with UC. CONCLUSIONS: Fetal and neonatal NT-proBNP levels
      are lower in IUGR compared with AGA, probably due to blood flow redistribution in
      IUGR and NT-proBNP placental transport in AGA. NT-proBNP levels peak on N1.

PMID- 18066965
TI  - In vitro testing of cyto- and genotoxicity of new porphyrin water-soluble metal
      derivatives.
AB  - Porphyrins and porphyrin derivatives have an outstanding potential for discovery
      of novel pharmacological agents due to their ability for numerous chemical
      modifications and a variety of mechanisms of biological effects. New water
      soluble Ag and Zn derivatives of tetrachloride meso-tetra (4-N-oxiethylpyridyl)
      porphyne were synthesized. Cyto- and genotoxicity of these substances were tested
      in vitro by the vital dye (trypan blue) exclusion and the micronucleus tests,
      respectively. Both metalloporphyrins were shown to be cytotoxic for Cos-7
      (fibroblast-like African green monkey kidney cells transformed by simian virus 40
      [SV40]), DU 145 (epithelial-like cells of human prostate carcinoma), and K-562
      (human chronic myeloid leukemia cells) cell lines. At the same time they did not
      cause chromosome fragmentation in K-562 cell line at as high concentrations as
      IC(50) (20 micromol/L for Ag and 70 micromol/L for Zn derivative). Thus, the
      metalloporphyrins tested meet at least two important demands to potential
      anticancer drugs as they combine the cytotoxicity with low genotoxicity. The
      three in vitro tumor models used are relevant to further in vitro and in vivo
      preclinical investigation of the studied metalloporphyrins as potential
      chemotherapeutics.

PMID- 18066966
TI  - Toxicity of binary chemical munition destruction products: methylphosphonic acid,
      methylphosphinic acid, 2-diisopropylaminoethanol, DF neutralent, and QL
      neutralent.
AB  - This paper reports the toxicity and environmental impact of neutralents produced
      from the hydrolysis of binary chemical agent precursor chemicals DF
      (methylphosphonic difluoride) and QL (2-[bis(1-methylethyl)amino]ethyl ethyl
      methylphosphonite). Following a literature review of the neutralent mixtures and
      constituents, basic toxicity tests were conducted to fill data gaps, including
      acute oral and dermal median lethal dose assays, the Ames mutagenicity test, and
      ecotoxicity tests. For methylphosphonic acid (MPA), a major constituent of DF
      neutralent, the acute oral LD(50) in the Sprague-Dawley rat was measured at 1888
      mg/kg, and the Ames test using typical tester strains of Salmonella typhimurium
      and Escherichia coli was negative. The 48-h LC(50) values for pH-adjusted DF
      neutralent with Daphnia magna and Cyprinodon variegatus were > 2500 mg/L and 1593
      mg/L, respectively. The acute oral LD(50) values in the rat for QL neutralent
      constituents methylphosphinic acid (MP) and 2-diisopropylaminoethanol (KB) were
      both determined to be 940 mg/kg, and the Ames test was negative for both. Good
      Laboratory Practice (GLP)-compliant ecotoxicity tests for MP and KB gave 48-h D.
      magna EC(50) values of 6.8 mg/L and 83 mg/L, respectively. GLP-compliant 96-h C.
      variegatus assays on MP and KB gave LC(50) values of 73 and 252 mg/L,
      respectively, and NOEC values of 22 and 108 mg/L. QL neutralent LD(50) values for
      acute oral and dermal toxicity tests were both > 5000 mg/kg, and the 48-h LD(50)
      values for D. magna and C. variegatus were 249 and 2500 mg/L, respectively. Using
      these data, the overall toxicity of the neutralents was assessed.

PMID- 18066967
TI  - Combined effects of vitamin C, vitamin E, and sodium selenate supplementation on
      absolute ethanol-induced injury in various organs of rats.
AB  - In this study, the effect of combination of vitamin C (ascorbic acid), vitamin E
      (alpha -tocopherol), and selenium (sodium selenate) on ethanol-induced liver and
      intestine injury in rats was investigated. The ethanol-induced injury was
      produced by the administration of 1 ml of absolute ethanol to each rats. Animals
      received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and sodium selenate (Se)
      (0.5 mg/kg) for 3 days; 1 h after the final antioxidant administration, they were
      sacrificed. Lipid peroxidation and glutathione levels, catalase (CAT), lactate
      dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase
      (GP(x)) activities were determined in liver and intestine tissues.
      Myeloperoxidase (MPO), aspartate transaminase (AST), alanine transaminase (ALT),
      alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) were determined in
      liver tissue. Also, CAT activity, urea, creatinine, uric acid, and total lipid
      levels were determined in serum samples. In the ethanol group, serum urea,
      creatinine, uric acid, and total lipid levels; liver and intestine LDH; liver
      MPO, AST, ALP, ALT, and GGT activities; and liver and intestine LPO levels
      increased, whereas serum CAT activity, liver and intestine GSH levels, and CAT,
      SOD, and GP(x) activities decreased. On the other hand, treatment with vitamin C,
      vitamin E, and Se reversed these effects. As a result of these findings, we can
      say that the combination of vitamin C, vitamin E, and selenium has a protective
      effect on ethanol-induced changes in lipid peroxidation, glutathione levels, and
      antioxidant enzyme activities in liver and intestine tissues, and in some serum
      parameters of rats.

PMID- 18066968
TI  - Detrimental effects of N-acetylcysteine plus desferoxamine combination in an
      experimental nephrotic syndrome model.
AB  - The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) and
      desferoxamine (DFO) administered alone or in combination together in rats with
      doxorubicin (DOX)-induced nephrotic syndrome, by monitoring oxidative stress
      parameters and trace elements in renal tissue and erythrocytes. Fifty-four male
      Sprague-Dawley rats were included the study. Equal volume of isotonic saline was
      injected to control rats. After DOX administration, the animals were divided into
      four experimental groups: (a) rats given only DOX; (b) rats treated with NAC; (c)
      rats treated with DFO; (d) rats treated with NAC plus DFO. The combination of N
      acetylcysteine and DFO has no beneficial effect on reducing proteinuria in
      experimentally nephrotic rats, although both of these agents ameliorate the
      condition when administered separately. It seems likely that detrimental effects
      of NAC plus DFO could be secondary to its effects on erythrocyte selenium levels
      demonstrated here. Consequently, the results may propose caution to the use of
      antioxidant therapeutic strategies such as NAC plus DFO against nephropathy.

PMID- 18066969
TI  - Evaluation of the mutagenic and genotoxic potential of ubiquinol.
AB  - Ubiquinol (the reduced form of coenzyme Q(10)) is the two-electron reduction
      product of ubiquinone (the oxidized form of coenzyme Q(10)), and has been shown
      to be an integral part of living cells, where it functions as an antioxidant in
      both mitochondria and lipid membranes. To provide information to enable a
      Generally Regarded as Safe (GRAS) evaluation for the use of ubiquinol in selected
      foods, a series of Organisation of Economic Cooperation and Development (OECD)
      and good laboratory practice (GLP) toxicological studies was conducted to
      evaluate the mutagenic and genotoxic potential of Kaneka QH brand of ubiquinol.
      Ubiquinol did not induce reverse mutations in Salmonella typhimurium strains
      TA100, TA1535, TA98, and TA1537 and Escherichia coli WP2uvrA at concentrations up
      to 5000 mu g/plate, in either the absence and presence of exogenous metabolic
      activation by rat liver S9. Likewise, ubiquinol did not induce chromosome
      aberrations in Chinese hamster lung fibroblast (CHL/IU) cells in short-term (6-h)
      tests with or without rat liver S9 at concentrations up to 5000 mu g/ml or in a
      continuous (24-h) treatment test at concentrations up to 1201 mu g/ml. Finally,
      no mortalities, no abnormal clinical signs, and no significant increase in
      chromosome damage were observed in an in vivo micronucleus test when administered
      orally at doses up to 2000 mg/kg/day. Thus, ubiquinol was evaluated as negative
      in the bacterial reverse mutation, chromosomal aberration, and rat bone marrow
      micronucleus tests under the conditions of these assays.

PMID- 18066970
TI  - Melatonin formation in pineal gland from rats with hexachlorobenzene experimental
      porphyria.
AB  - Hexachlorobenzene produces an experimental hepatic porphyria in rats, which is
      similar to human porphyria cutanea tarda, with hyperpigmentation as one of its
      characteristic features. Alterations in tryptophan metabolism have been
      previously observed in this chronic porphyria. Melatonin formation from
      tryptophan via serotonin shows diurnal rhythmicity in the pineal gland, and
      higher values are observed during the dark phase of an imposed light-dark cycle.
      The purpose of this study was to determine the contents of tryptophan and its
      metabolites in pineal gland of normal and hexachlorobenzene-treated rats in order
      to find alterations potentially related to porphyria cutanea tarda. Results show
      that in animals with this experimental porphyria some tryptophan metabolite
      levels (serotonin and 5-hydroxyindoleacetic acid) increase only during the light
      period, whereas tryptophan content remained equal to the controls. Hydroxyindole
      O-methyltransferase activity also increases by light in pineal gland from
      hexachlorobenzene-treated rats. On the other hand, tryptophan is converted to
      melatonin in the dark period, but this route is not exacerbated in
      hexachlorobenzene porphyria. The relevance of these alterations is discussed in
      relation to hyperpigmentation, neoplastic and oxidative stress processes
      associated with this porphyria.

PMID- 18066971
TI  - Phospholipase A2 activation regulates cytotoxicity of methylmercury in vascular
      endothelial cells.
AB  - Mercury has been identified as a risk factor for cardiovascular disease among
      humans. Through diet, mainly fish consumption, humans are exposed to
      methylmercury, the biomethylated organic form of environmental mercury. As the
      endothelium is an important player in homeostasis of the cardiovascular system,
      here, the authors tested their hypothesis that methylmercury activates the lipid
      signaling enzyme phospholipase A(2) (PLA(2)) in vascular endothelial cells (ECs),
      causing upstream regulation of cytotoxicity. To test this hypothesis, the authors
      used bovine pulmonary artery ECs (BPAECs) cultured in monolayers, following
      labeling of their membrane phospholipids with [(3)H]arachidonic acid (AA). The
      cells were exposed to methylmercury chloride (MMC) and then the release of free
      AA (index of PLA(2) activity) and lactate dehydrogenase (LDH; index of
      cytotoxicity) were determined by liquid scintillation counting and
      spectrophotometry, respectively. MMC significantly activated PLA(2) in a dose
      dependent (5 to 15 microM) and time-dependent (0 to 60 min) fashion. Sulfhydryl
      (thiol-protective) agents, calcium chelators, antioxidants, and PLA(2)-specific
      inhibitors attenuated the MMC-induced PLA(2) activation, suggesting the role of
      thiols, reactive oxygen species (ROS), and calcium in the activation of PLA(2) in
      BPAECs. MMC also induced the loss of thiols and increase of lipid peroxidation in
      BPAECs. MMC induced cytotoxicity in BPAECs as observed by the altered cell
      morphology and LDH leak, which was significantly attenuated by PLA(2) inhibitors.
      This study established that PLA(2) activation through thiols, calcium, and
      oxidative stress was associated with the cytotoxicity of MMC in BPAECs, drawing
      attention to the involvement of PLA(2) signaling in the methylmercury-induced
      vascular endothelial dysfunctions.

PMID- 18066972
TI  - Mitochondrial bioenergetics after nine-day treatment regimen with benzonidazole
      in rats.
AB  - The bioenergetics of cardiac, liver, and kidney mitochondria after 9-day
      treatment regimen with benzonidazole was studied in rats. The drug was given by
      oral gavage to adult male Sprague-Dawley rats for 9 consecutive days (100 mg
      benzonidazole/kg body weight as daily dose). The assayed mitochondrial
      bioenergetic parameters were the state 4, state 3, respiratory control,
      efficiency of oxidative phosphorylation, and the activity of the mitochondrial
      ATP synthase. The results showed that mitochondrial parameters were not altered
      statistically after in cardiac and kidney mitochondria, but respiratory control
      in liver mitochondria was statistically increased with benzonidazole treatment.
      This change was likely due to a slight decrease in state 4 bioenergy metabolism.
      These results indicate that 9-day benzonidazole treatment regimen had no negative
      effect on cardiac, liver, and kidney mitochondrial energy metabolism but
      increased respiratory control in rat liver mitochondria.

PMID- 18066973
TI  - 2006-2007 National Health Law Moot Court Competition.

PMID- 18066974
TI  - 2006-2007 National Health Law Moot Court Competition: best brief.

PMID- 18066975
TI  - Health privacy in the electronic age.

PMID- 18066976
TI  - The Wal-Martization of health care.

PMID- 18066977
TI  - The expert heightened disclosure requirement and the physician-defendant in
      medical negligence cases. Rejecting the substance-based rule 26 approach.

PMID- 18066978
TI  - Protect the heart of an athlete. The need for uniform legal and medical standards
      in pre-participation athletic physical examinations.

PMID- 18066979
TI  - Where have all the parents gone? Do efforts to regulate food advertising to curb
      childhood obesity pass constitutional muster?

PMID- 18066982
TI  - Obituary. David Abraham Goitein Galton.

PMID- 18066984
TI  - Godwits and blast crises: in memory of David Galton.

PMID- 18066985
TI  - FAB and beyond.

PMID- 18066986
TI  - The changing face of chronic lymphocytic leukemia.

PMID- 18066987
TI  - Distinguishing between entities--rationally based advances in the therapy of
      follicular lymphoma.

PMID- 18066988
TI  - David Galton, myelodysplasia and little me!

PMID- 18066989
TI  - Chronic myeloid leukemia--therapy in the 20th and 21st centuries.

PMID- 18066990
TI  - David Galton and the evolution of somatic cell populations.

PMID- 18066991
TI  - MRC trials in acute myeloblastic luekemia: where have we got to?

PMID- 18066993
TI  - David A. G. Galton: a personal perspective.

PMID- 18066992
TI  - David Galton--the thesis years.

PMID- 18066994
TI  - David A. G. Galton and the F.A.B. group.

PMID- 18066995
TI  - David Galton--a friend and teacher.

PMID- 18066996
TI  - David Galton--reminiscences.

PMID- 18066998
TI  - How to prevent deep vein thrombosis in myeloma patients receiving thalidomide or
      lenalidomide.

PMID- 18066999
TI  - What is the correct philosophy for the treatment of multiple myeloma?

PMID- 18067000
TI  - Lessons of war: progress in transplant conditioning regimens.

PMID- 18067001
TI  - FLT3 internal tandem duplication in low risk MDS: clinical and basic science
      relevance.

PMID- 18067002
TI  - Is autologous progenitor cell mobilization getting any easier?

PMID- 18067003
TI  - Chronic lymphocytic lymphoma: another example of parental favoritism?

PMID- 18067004
TI  - Viral infection or reactivation in patients during treatment with dasatinib: a
      call for screening?

PMID- 18067005
TI  - Strategies for overcoming imatinib resistance in chronic myeloid leukemia.
AB  - Imatinib was the first treatment for chronic myeloid leukemia (CML) that
      specifically targeted the causative BCR-ABL oncoprotein, and represented a major
      therapeutic advance in this disease; however, some patients develop resistance or
      intolerance. Resistance can be classified as BCR-ABL-dependent (e.g., mutation in
      the BCR-ABL gene) or BCR-ABL-independent (alternative pathways of disease
      progression, e.g., SRC-family tyrosine kinases). The investigation of therapeutic
      options post-imatinib failure resulted in the development and regulatory approval
      of dasatinib, a BCR-ABL and SRC-family kinase inhibitor. Dasatinib is active
      across all phases of CML and Philadelphia chromosome-positive acute lymphoblastic
      leukemia, and demonstrates activity in almost all imatinib-resistant mutations.
      Other therapeutic options are also under investigation, with nilotinib being the
      most clinically advanced. Nilotinib is an analog of imatinib with similar
      multiple kinase targets, but without inhibition of SRC, and reduced in vitro
      activity against BCR-ABL P-loop mutations compared with dasatinib. Similar to
      dasatinib, nilotinib has no activity against T315I mutations. The availability of
      dasatinib and development of other tyrosine kinase inhibitors provide positive
      prospects for patients with imatinib-resistant or -intolerant CML. Here, we
      discuss several of these new strategies for treating patients after imatinib
      failure.

PMID- 18067006
TI  - Myeloma cells and bone marrow osteoblast interactions: role in the development of
      osteolytic lesions in multiple myeloma.
AB  - Bone destruction is the hallmark of multiple myeloma (MM) due to the high
      capacity of malignant plasma cells to induce a severe imbalance of bone
      remodeling. Growing evidences suggest that MM cell interactions with bone marrow
      (BM) osteoblast have a critical role in the pathophysiology of osteolytic
      lesions. Indeed histomorphometric studies have demonstrated that MM patients with
      osteolytic bone lesions have lower numbers of osteoblasts and decreased bone
      formation together with osteoclast activation. Recently, the biological
      mechanisms involved in the osteoblast inhibition induced by MM cells have begun
      to be elucidated, underlying the main role of the block of osteoblast
      differentiation in the development of bone lesions. In this article, we summarize
      the main mechanisms regulating MM cell and osteoblast interactions.

PMID- 18067007
TI  - Prophylactic low-dose aspirin is effective antithrombotic therapy for combination
      treatments of thalidomide or lenalidomide in myeloma.
AB  - Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE),
      and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone
      increases this risk. This report describes the use of low-dose aspirin (81 mg) as
      primary thromboprophylaxis in three series of MM patients receiving thalidomide
      or lenalidomide with other drugs. In the first regimen (clarithromycin,
      thalidomide, dexamethasone), initiation of low-dose aspirin negated the
      occurrence of any further TE. In a second study, prophylactic aspirin given with
      thalidomide/dexamethasone resulted in a rate of TE similar to that seen with
      dexamethasone alone (without aspirin). A third study (n = 72) evaluated
      thrombosis rates with aspirin and a lenalidomide-containing regimen
      (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of
      thromboembolism, five were associated with aspirin interruption or poor
      compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with
      these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM
      patients receiving immunomodulatory drugs with corticosteroids is warranted.

PMID- 18067008
TI  - Combination of rituximab and oral melphalan and prednisone in newly diagnosed
      multiple myeloma.
AB  - Clonotypic B lymphocytes may underlie relapse of patients with multiple myeloma.
      Rituximab, a CD20 monoclonal antibody, may result in eradication of the
      monoclonal B cells. We conducted a phase II study of rituximab in combination
      with melphalan and prednisone therapy (MP) followed by rituximab maintenance in
      newly diagnosed multiple myeloma patients. Sixteen patients (35%) had CD20
      positive bone marrow plasma cells, while 9 patients (20%) had unknown CD20
      status. No patient had a complete remission, 26 patients (58%) had a partial
      response, 6 patients (13%) had a minimal response, and 8 patients (18%) had
      stable disease. The median event-free survival was 14 months, and the 7-year
      overall survival was 30%. The toxicity of the combination was overall manageable
      and consistent with what is generally noted with MP chemotherapy. The combination
      of rituximab to MP therapy did not result in improved response rate or event-free
      survival.

PMID- 18067009
TI  - Escalation therapy with bortezomib, dexamethasone and bendamustine for patients
      with relapsed or refractory multiple myeloma.
AB  - In order to improve remission rates without causing undue toxicity, we treated 50
      patients with relapsed/refractory multiple myeloma according to an institutional
      sequential treatment algorithm. Bortezomib was given as monotherapy (1.3 mg/m(2)
      on day 1 + 4 + 8 + 11) followed by the addition of dexamethasone in a first (40
      mg on day 1 + 4 + 8 + 11) and bendamustine (50 - 100 mg/m(2) on day 1 + 8) in a
      second escalation step for patients with less than a minor response. Bortezomib
      monotherapy was sufficient in 23 (46%) patients, treatment escalation with
      dexamethasone was necessary in 20 (40%) patients and 7 (14%) patients needed
      triple combination therapy. Overall response rate was 84% while toxicity was
      manageable. Median time to progression and overall survival were 8 and 20 months,
      respectively. In conclusion, this treatment algorithm resulted in responses in
      the majority of heavily pre-treated patients while at the same time restricting
      the toxicity of triple combination therapy to only 14% of non-responding
      patients.

PMID- 18067010
TI  - Fludarabine and treosulfan: a novel modified myeloablative regimen for allogeneic
      hematopoietic stem-cell transplantation with effective antileukemia activity in
      patients with acute myeloid leukemia and myelodysplastic syndromes.
AB  - Allogeneic stem-cell transplantation (SCT) is potentially curative treatment for
      AML and MDS. New conditioning regimens are continuously explored trying to reduce
      toxicity while maintaining antileukemia effect. Treosulfan is an alkylating agent
      with in vitro cytotoxicity against leukemia as well as myeloablative and
      immunosuppressive properties when used in escalated doses. We explored a regimen
      of fludarabine (30 mg/m(2) x 5) and treosulfan (12 gr/m(2) x 3) in 24 patients,
      median age 55 years (range, 30-69), with AML (n = 19) or MDS (n = 5), not
      eligible for standard myeloablation. Donors were HLA-matched siblings (n = 11) or
      matched-unrelated (n = 13). Twenty-one patients engrafted within a median of 15
      days. Extramedullary toxicity was relatively limited. The incidence of acute and
      chronic GVHD was 15% and 47%, respectively. With median follow-up of 19 months
      (range, 8 - 34), 16 patients are alive and 8 died (relapse-2, treatment-related
      6). Two-year disease-free survival rate was 60% (95% CI, 39-81). The cumulative
      incidence of relapse was only 15% (95% CI, 5 - 44) while nonrelapse mortality
      rate was 25% (95% CI, 13-50). The fludarabine/treosulfan regimen can be
      considered a fully intensive, modified myeloablative regimen with effective
      antileukemia activity and acceptable toxicity in patients with AML/MDS not
      eligible for standard myeloablation, and merits further study in larger scale
      studies.

PMID- 18067011
TI  - Paclitaxel and filgrastim for hematopoietic progenitor cell mobilization in
      patients with hematologic malignancies after failure of a prior mobilization
      regimen.
AB  - Paclitaxel and G-CSF have been evaluated for HPC mobilization in breast cancer
      and found to have tolerable toxicity with a predictable time to initiate
      leukapheresis. However, this approach has not been reported in patients with
      hematologic malignancies failing prior mobilization. We report a case-series of
      26 adults given paclitaxel and G-CSF for HPC mobilization after failure of an
      initial mobilization. Patients received paclitaxel 250 mg/m(2) followed by G-CSF
      10-16 mcg/kg/day. Compared to the initial regimen, paclitaxel mobilization
      produced greater CD34+ cell yields (median 1.53 x 10(6) CD34+ cells/kg vs. 0.79 x
      10(6) CD34+ cells/kg, p = 0.004). Seventy-six percent of patients initiated
      leukapheresis on day 8, the remainder on day 9 or 10. Three patients developed
      febrile neutropenia resulting in one death prior to leukapheresis. Overall, 73%
      of patients proceeded with autologous HPC transplant. This case-series suggests
      paclitaxel may be an option for HPC mobilization in patients failing prior
      regimens.

PMID- 18067013
TI  - Thrombocytosis in myelodysplastic and myelodysplastic/myeloproliferative
      syndromes.
AB  - Thrombocytosis at diagnosis is uncommon in myelodysplastic (MDS) and
      myelodysplastic/myeloproliferative (MDS/MPD) syndromes. We conducted a
      retrospective analysis to determine the clinical and haematopathological features
      of such patients, and the effect of thrombocytosis on prognosis. Of the 388
      patients diagnosed with MDS from 1980 - 2006, 31 presented with thrombocytosis.
      The majority (71%) had low risk features and a low incidence of spontaneous
      bleeding or thrombo-embolic events. Compared to a case-matched control group of
      MDS and MDS/MPD patients without thrombocytosis of similar ages and IPSS scores,
      patients with thrombocytosis had a slightly lower probability of progression to a
      higher grade of MDS (P = 0.03), equivalent risk of transformation to acute
      myeloid leukemia (AML), and a trend (P = 0.07) towards longer overall survival
      (median 35.4 months compared to 27.6 months for controls).

PMID- 18067012
TI  - Characteristics of and risk factors for pneumonia in patients with hematological
      malignancies developing fever after autologous blood stem cell transplantation.
AB  - We analyzed the incidence, etiology, risk factors and outcomes of 49 episodes of
      pneumonia that developed in 326 adult patients undergoing autologous stem-cell
      transplantation (ASCT) from January 1990 to December 2005. The median time for
      the onset of pneumonia after transplantation was 11 days (range 0-148). Empirical
      antibiotic therapy in patients with pneumonia consisted of piperacillin
      tazobactam (20 cases, 49%), third-generation cephalosporin (11 cases, 27%) and
      carbapenem (8 cases, 19%). Multivariate analysis showed that a higher risk of
      pneumonia could be predicted for patients with myeloma (P = 0.006) and for
      patients with an absolute neutrophil count <0.5 x 10(9)/L >7 days (P = 0.008).
      Cumulative incidence of transplant-related mortality at 6 months was 51% versus
      8% for patients with or without pneumonia, respectively (P = 0.001). Pneumonia
      after ASCT is a severe complication more commonly observed in patients with
      myeloma and with prolonged duration of neutropenia.

PMID- 18067014
TI  - Estimated number of cases, regional distribution and survival of patients
      diagnosed with acute myeloid leukemia between 1996 and 2000 in Rio Grande do Sul,
      Brazil.
AB  - Rio Grande do Sul (RS), in South Brazil, with about 10 million inhabitants, is
      known for its agricultural activities and consequent increased human exposure to
      toxic agents. Patients with de novo acute myeloid leukemia (AML) were included
      based on information retrieved from all referral hospitals in RS between 1996 and
      2000. A total of 532 patients were registered. Median age at diagnosis was 42
      years. The estimated annual incidence was 1.11 cases/100,000 inhabitants/year.
      There was an estimated incidence of 0.5-1 case per 100,000 inhabitants up to the
      age of 45 years, and of 3.5 cases per 100,000 inhabitants aged 70 years and
      older, with no geographical clusters. The mean 5-year survival rate was 17% for
      all cases. There was an increased number of M3 cases, as already described for
      individuals of Latin-American and the mortality rate was similar to that
      described in the literature.

PMID- 18067015
TI  - Birth order pattern in the inheritance of chronic lymphocytic leukaemia and
      related lymphoproliferative disease.
AB  - Rank order of affected offspring in a sibship can inform on epigenetic factors in
      disease susceptibility. Here we report an analysis of birth order in 32 families
      segregating chronic lymphocytic leukaemia (CLL) and other B-cell
      lymphoproliferative disorders. A paternal-offspring, but not a maternal-offspring
      birth rank order was observed. Cox regression analysis provided relative risks
      (RR) for paternal and maternal transmission of 3.60 (CI 95%: 1.54 - 8.42; P =
      0.0005) and 1.64 (CI 95%: 0.90 - 3.01; P = 0.096), respectively. The significance
      of paternal and maternal transmission of CLL-CLL pairs employing Haldane and
      Smith's test were 0.006 and 0.63, respectively. There was no evidence of a
      relationship between parental age and birth order. The genetic mechanism behind
      the birth order effect observed is discussed in the light of non-Mendelian
      imprinting and pregnancy related microchimerism.

PMID- 18067016
TI  - Biologic predictors in follicular lymphoma: importance of markers of immune
      response.
AB  - We sought to identify biologic indicators of prognosis in a series of 94
      follicular lymphoma (FL) patients, focusing on markers of the host immune
      response as well as of B-cell maturation. Immune response was assessed with
      immunostains for CD68 (for lymphoma-associated macrophages, LAMs) and FOXP3
      (regulatory T-cells). Lymphoma cells were evaluated for expression of bcl-2,
      CD10, and MUM-1. Clinical data were obtained for FLIPI, presence of bulky
      disease, presence of B-symptoms, treatment, and overall survival (OS). For the 69
      initially treated patients, extrafollicular CD68+ cells (ef-CD68) and follicular
      FOXP3+ cells (f-FOXP3) were associated with shorter OS, while receipt of
      rituximab was associated with longer OS. Multivariable analysis showed ef-CD68
      was the only independent factor associated with shorter OS. In subset analysis,
      ef-CD68 remained statistically significant in rituximab-naive but not rituximab
      treated patients. We confirm the importance of LAMs and f-FOXP3 as predictors of
      OS in FL.

PMID- 18067017
TI  - Methylprednisolone-rituximab is an effective salvage therapy for patients with
      relapsed chronic lymphocytic leukemia including those with unfavorable
      cytogenetic features.
AB  - Chronic lymphocytic leukemia (CLL) patients with aggressive molecular
      characteristics such as deletion of 17p13.1 do not respond to conventional
      treatments and have a shorter survival. Studies suggest that high-dose
      methylprednisolone (HDMP) has activity in such patients and combining HDMP with
      rituximab may enhance efficacy. We identified 37 patients with CLL treated with
      the HDMP-rituximab who had follow-up at Mayo Clinic. Nine of 27 (33%) had
      deletion of 17p13.1 and six of 27 (22%) had deletion of 11q22.3. After a median
      of one cycle of HDMP-rituximab, 29 (78%) patients had an objective response
      according to the National Cancer Institute CLL Working Group Criteria including
      five of nine patients with deletion of 17p13.1. Eight (22%) patients had a
      complete clinical response. Although well tolerated, 11 (29%) patients developed
      infectious complications before completing one month of therapy. Three-year
      survival was 41% (95% CI: 26 - 66%). HDMP-rituximab is an active regimen in
      patients with relapsed, refractory, and cytogenetically high-risk CLL. Further
      evaluation of this regimen in controlled trials appears warranted.

PMID- 18067018
TI  - Specific pattern of protein expression in acute myeloid leukemia harboring FLT3
      ITD mutations.
AB  - FLT3 activating mutations can be detected in about 35% of acute myeloid leukemia
      (AML). FLT3 internal tandem duplications (FLT3-ITD) represent the majority of
      FLT3 mutations (25 - 30%) while FLT3-TKD (tyrosine kinase domain) mutations can
      be found in about 7% of AML patients. In this study, we addressed the question
      whether especially primary AML cells carrying FLT3-ITD mutations show differences
      in terms of their protein expression pattern compared to FLT3 wild-type blasts.
      We investigated bone marrow samples that were isolated at diagnosis from 36 AML
      patients expressing either FLT3 wild-type (n = 16) or an activating FLT3 mutation
      (FLT3-ITD, n = 15; FLT3-TKD, n = 5). Proteomic analysis was performed by means of
      surface enhanced laser desorption/ionization-time of flight (SELDI-TOF) mass
      spectrometry which has shown its high efficiency in finding biomarkers in solid
      tumors. Here, we demonstrate that a large series of proteins is differently
      expressed in primary AML blasts harboring FLT3-ITD mutations. Furthermore, there
      are also significant differences of the protein expression profile between FLT3
      ITD and FLT3-TKD mutations. Interestingly, further analysis of FLT3-ITD positive
      AML according to its response to the induction chemotherapy demonstrates putative
      prognostic markers for this subgroup of AML. We suggest that SELDI-TOF mass
      spectrometry represents a promising tool of proteomic analysis of AML that might
      help to establish new prognostic markers in AML.

PMID- 18067019
TI  - CD52 over-expression affects rituximab-associated complement-mediated
      cytotoxicity but not antibody-dependent cellular cytotoxicity: preclinical
      evidence that targeting CD52 with alemtuzumab may reverse acquired resistance to
      rituximab in non-Hodgkin lymphoma.
AB  - In an attempt to define mechanisms by which B-cell non-Hodgkin lymphoma (NHL) may
      escape rituximab immunotherapy, we developed several rituximab-resistant cell
      lines (RRCL) generated from the rituximab-sensitive cell lines (RSCL) Raji and
      RL. Rituximab resistance was associated with CD20 downregulation and upregulation
      of CD52 and the complement inhibitory proteins (CIPs) CD55 and CD59. No
      significant alemtuzumab-associated complement-mediated cell lysis (CMC) or
      antibody-dependent cellular cytotoxicity (ADCC) was demonstrated in RSCL. In
      contrast, in vitro exposure of RRCL to alemtuzumab resulted in a significant
      degree of CMC and ADCC. Of note, in vitro blocking of CD52 with anti-CD52
      F(ab')(2) fractions in RRCL improved rituximab-associated CMC as compared to
      unblocked RRCL. Our current data provides a basis for further evaluation of
      alemtuzumab-based clinical trials for patients with rituximab-resistant NHL.

PMID- 18067020
TI  - Analysis of FLT3 gene mutations in de novo myelodysplastic syndromes. FLT3
      internal tandem duplication detected in a case of refractory anemia.

PMID- 18067021
TI  - Complete molecular remission induced by concomitant cladribine--rituximab
      treatment in a case of multi-resistant hairy cell leukemia.

PMID- 18067022
TI  - Recurrent hemophagocytic lymphohistiocytosis accompanied by Kikuchi's disease.

PMID- 18067023
TI  - Phrenic nerve paralysis due to vincristine.

PMID- 18067024
TI  - Pregnancy in patients with chronic myeloid leukemia treated with imatinib.

PMID- 18067025
TI  - Characterization of high-hyperdiploidy in childhood acute lymphoblastic leukemia
      with gain of a single chromosome 21.

PMID- 18067026
TI  - Parvovirus B19 acute infection and a reactivation of cytomegalovirus and
      herpesvirus 6 in a chronic myeloid leukemia patient during treatment with
      dasatinib (BMS-354825).

PMID- 18067027
TI  - Lenalidomide-associated hypothyroidism.

PMID- 18067029
TI  - Transdisciplinary tobacco use research: a decade of progress. Introduction.

PMID- 18067030
TI  - Smoking to self-medicate attentional and emotional dysfunctions.
AB  - Individuals with attentional and emotional dysfunctions are most at risk for
      smoking initiation and subsequent nicotine addiction. This article presents
      converging findings from human behavioral research, brain imaging, and basic
      neuroscience on smoking as self-medication for attentional and emotional
      dysfunctions. Nicotine and other tobacco constituents have significant effects on
      neural circuitry underlying the regulation of attention and affect. Age, sex,
      early environment, and exposure to other drugs have been identified as important
      factors that moderate both the effects of nicotine on brain circuitry and
      behavior and the risk for smoking initiation. Findings also suggest that the
      effects of smoking differ depending on whether smoking is used to regulate
      attention or affect. Individual differences in the reinforcement processes
      underlying tobacco use have implications for the development of tailored smoking
      cessation programs and prevention strategies that include early treatment of
      attentional and emotional dysfunctions.

PMID- 18067031
TI  - Developing the science base for reducing tobacco harm.
AB  - The University of Minnesota Transdisciplinary Tobacco Use Research Center has
      been examining the multiple dimensions and the scientific evidence required to
      determine the feasibility of tobacco harm reduction as a means to reduce tobacco
      related mortality and morbidity. Because of the complexity associated with
      exploring this area, an interdisciplinary approach is necessary. The research
      components that have been of particular focus at our center include (a)
      developing and validating biomarkers of tobacco-related exposure and toxicity,
      (b) developing animal models and designing studies with humans to assess a
      variety of smoking reduction approaches and potential reduced exposure products,
      and (c) determining individual differences in response to these interventions and
      products. A description of the ongoing activities and challenges in these areas
      is provided, along with projected directions for the future.

PMID- 18067033
TI  - Communications strategies to broaden the reach of tobacco use research: examples
      from the Transdisciplinary Tobacco Use Research Centers.
AB  - One of the initial goals of the Transdisciplinary Tobacco Use Research Center
      (TTURC) initiative was to broaden the traditional model of how research results
      are communicated, going beyond scholarly journals, as a way to accelerate the
      discovery-to-dissemination process. A strategy in meeting this goal was the
      establishment of a communications program at the seven initially funded TTURCs.
      This paper reports the results of the communications efforts from the TTURC
      initiative. Specific communications activities are described, highlighting
      efforts to reach broad audiences and increase the impact of the research. We
      present lessons learned from this effort to enhance knowledge translation through
      the development of communications infrastructure and dissemination activities,
      focusing especially on the guidance they offer for the development of future
      research-communications partnerships.

PMID- 18067032
TI  - Time to first cigarette in the morning as an index of ability to quit smoking:
      implications for nicotine dependence.
AB  - An inability to maintain abstinence is a key indicator of tobacco dependence.
      Unfortunately, little evidence exists regarding the ability of the major tobacco
      dependence measures to predict smoking cessation outcome. This paper used data
      from four placebo-controlled smoking cessation trials and one international
      epidemiological study to determine relations between cessation success and the
      Fagerstrom Test for Nicotine Dependence (FTND), the Heaviness of Smoking Index,
      the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking
      Dependence Motives. Results showed that much of the predictive validity of the
      FTND could be attributed to its first item, time to first cigarette in the
      morning, and this item had greater validity than any other single measure. Thus
      the time-to-first-cigarette item appears to tap a pattern of heavy,
      uninterrupted, and automatic smoking and may be a good single-item measure of
      nicotine dependence.

PMID- 18067034
TI  - Translating basic science to improve pharmacotherapy for nicotine dependence.
AB  - Nicotine dependence has a complex multifactorial etiology, underscoring the value
      of applying a transdisciplinary research model. The important goal of treating
      nicotine dependence can be realized by transdisciplinary research that translates
      discoveries in basic neuroscience, pharmacology, genetics, and behavioral science
      to develop new treatment models that can be translated readily into the clinic
      and community. As part of this special issue highlighting work at the
      Transdisciplinary Tobacco Use Research Centers (TTURCs), we describe
      transdisciplinary research at the University of Pennsylvania TTURC aimed at
      elucidating the neurobiological and genetic basis of nicotine dependence, the
      development of novel medications, and the translation of this research to
      practice.

PMID- 18067035
TI  - Comorbidity between depression and smoking moderates the effect of a smoking
      prevention program among boys in China.
AB  - Smoking prevention programs based on social influences have reduced smoking
      prevalence among youth. However, these effects have not been replicated
      consistently. It is possible that individuals and populations with different
      dispositional and behavioral characteristics will experience different program
      effects. This study explored a possible moderation of program effect by
      comorbidity between depression and smoking (CoM). Data for this analysis were
      from 2,450 seventh-grade youth (51% boys) who participated in the Wuhan (China)
      Smoking Prevention Trial (WSPT). WSPT was a randomized, controlled, 14-session,
      middle-school-based smoking prevention trial. Baseline and 1-year follow-up
      surveys were administered. The moderation effect between the program and CoM was
      tested on 1-year change in recent smoking. The CoM indicator was defined
      dichotomously as monthly cigarette use and high in depression level (among the
      top 20% in the sample). At baseline, a total of 26 girls and 60 boys were
      identified to have CoM. Among boys (but not girls), CoM significantly moderated
      the program effect on recent smoking (p = .01). The program effect among boys
      with CoM was 4.17 (95% CI 1.47-11.76) times larger than those without CoM. Among
      boys with CoM, the odds ratio of recent smoking was 0.18 (95% CI 0.06-0.55) for
      program vs. control condition. Among those without CoM, the program did not
      reduce the odds of recent smoking significantly (OR = 0.74, 95% CI 0.37-1.48).
      The study demonstrated that smoking prevention program effects can vary with
      individual characteristics, in this case comorbidity between depression and
      smoking. These findings may help explain the inconsistency in program effects
      across studies and populations. The findings also may contribute to the design of
      future programs to address the needs of defined populations and individuals with
      specific characteristics.

PMID- 18067036
TI  - Smoking in college freshmen: University Project of the Tobacco Etiology Research
      Network (U pTERN).
AB  - UpTERN, a study conducted by the Tobacco Etiology Research Network (TERN), was
      designed to examine trajectories of change in smoking behavior and the emergence
      of dependence over the course of the freshman year from a large sample of college
      students. The project included extensive quantitative and qualitative assessments
      of participants. In the first phase, screener data were collected from 4,690
      freshmen entering Purdue University in the fall of 2002. In the second phase, 912
      students were enrolled from the 2,001 who reported some prior exposure to smoking
      cigarettes in the first phase. These students provided extensive baseline
      information on a web-based assessment protocol administered in the week prior to
      the beginning of classes in the fall semester. In the third phase, these students
      participated in a web-based assessment administered for 35 consecutive weeks.
      Approximately 88% of the sample completed the web-based assessment each week.
      This report describes the rationale for the project and provides an overview of
      the constructs targeted across the research. In addition, the research methods,
      procedures, and assessments are discussed. Findings are reported for day-to-day
      patterns of smoking as well as alcohol and marijuana use across the 35 weeks of
      assessment. Finally, selected results from reports using data generated from this
      project are summarized, including analyses of patterns of smoking over time,
      associations between daily cigarette smoking and alcohol use, evaluations of the
      nature of nicotine dependence in low-level smokers, an exploration of early
      cigarette-use episodes in novice smokers, and a consideration of the role of
      descriptive and injunctive norms from romantic partners and friends in predicting
      cigarette smoking over time.

PMID- 18067037
TI  - Regulation and pathological role of bid in ischemic acute kidney injury.
AB  - Bid, a BH3-only member of the Bcl-2 family proteins, is most abundantly expressed
      in the kidneys. Recent research has shown Bid activation in renal tubular cells
      in vitro following ATP-depletion and hypoxic injury, and also in vivo during
      renal ischemia-reperfusion in rats and mice. Importantly, Bid-deficient mice are
      resistant to ischemic kidney injury. Targeting Bid may therefore offer a new
      strategy for the treatment of acute renal failure associated with ischemia
      reperfusion.

PMID- 18067038
TI  - Local calcitriol injections as a suppressive treatment of secondary
      hyperparathyroidism in chronic dialysis patients.
AB  - AIM: A prospective study was made of the effectiveness of repeatable local
      calcitriol injections therapy to suppress secondary hyperparathyroidism resistant
      to conventional therapy in chronic dialysis patients. METHODS: Under
      ultrasonographic guidance, six injections at an interval of two days were
      performed in 14 chronic dialysis patients. The total amount of calcitriol to be
      injected each time was estimated as 100% of the calculated gland volume.
      Calcitriol was given in doses 1 mug of medicine per 1 cubic cm (as measured by
      USG) of parathyroid tissue. Parathormone concentration, total calcium, ionized
      calcium, phosphate, and alkaline phosphatase levels were assessed on the first
      and last day of the treatment period. RESULTS: Prior to therapy, the mean gland
      volumes were 0.62 (0.15-3.0) ml, and they increased to 0.85 (0.2-3.9) after 14
      days (NS). Seven patients were found to have decreased their PTH levels to 909 +/
      387 pg/mL after 14 days of treatment when compared with the first day mean
      values of 1588 +/- 440 pg/mL (p < 0.05). After completion of the therapy, four
      patients were reported to be free from any clinical symptoms of ostalgia or
      arthralgia. Others reported an alleviation of pain. CONCLUSIONS: Parathyroid
      adenoma injection is an alternative method of treatment for some patients
      resistant to treatment by means of vitamin D3 pulses or intravenous
      administration of calcitriol. The success of treatment is to a great extent
      determined by proper selection of patients and the taking of decisions when the
      period of secondary hyperparathyroidism is not very advanced.

PMID- 18067039
TI  - Relationship between GSTs gene polymorphism and susceptibility to end stage renal
      disease among North Indians.
AB  - BACKGROUND AND OBJECTIVE: Glutathione-S-transferase (GST) is the superfamily of
      genes that provides protection to the cells against reactive oxygen species and
      plays a vital role in phase II of biotransformation of many substances.
      Overexpression of GST (EC 2.5.1.18) has been documented in the erythrocytes of
      patients with chronic renal failure, which may be of clinical relevance. Keeping
      this background in mind, we have investigated the relationship between human GST
      gene polymorphism in end stage renal disease (ESRD) patients. DESIGN AND METHODS:
      We have assessed 184 patients with ESRD and 569 age-and sex-matched controls from
      North India. The GSTT1 and GSTM1 null genotypes were identified by polymerase
      chain reaction (PCR). GSTP1-313 A/G mutation was determined by PCR followed by
      restriction enzyme digestion. RESULTS: The gene frequency of GSTM1, GSTT1, and
      GSTP1 polymorphism were evaluated. We observed that GSTM1 null genotype was
      present in 46.74% of the ESRD patients while GSTT1 null genotype was present in
      58.7% of the ESRD subjects. The genotypic distribution of GSTP1 was
      Ile(105)/Ile(105) in 47.3%, Ile(105)/Val(105) in 30.97% and Val(105)/Val(105) in
      21.74% of ESRD patients. There was a significant association of null alleles of
      the GSTM1 (p = 0.0386; OR = 1.445, 95% CI = 1.033-2.021) and GSTT1 (p < or =
      0.0001; OR = 4.568, 95% CI = 3.215-6.492) and in the -313 G alleles (Val) of the
      GSTP1 gene (p = 0.0032; OR = 1.956, 95% CI = 1.265-3.024) with end stage renal
      disease. The combined analysis of the three genotypes showed a further increased
      risk to ESRD (p < or = 0.0001; OR = 9.01, 95% CI = 5.55-14.626). INTERPRETATIONS
      AND CONCLUSIONS: The null / low polymorphism of the detoxifying enzymes GSTT1,
      GSTM1, and GSTP1 are associated with the risk of developing ESRD in North Indian
      patients.

PMID- 18067040
TI  - Assessment of health-related fitness in the patients with end-stage renal disease
      on hemodialysis: using Eurofit Test Battery.
AB  - The main objectives of this study were to evaluate the health-related physical
      fitness for the patients with end-stage renal disease on hemodialysis and
      determine the suitability of Eurofit Test Battery for adults to decide their
      health-related physical fitness level. Eighteen patients with end-stage renal
      disease (ESRD) on hemodialysis (age 49.7+17.9, 10 female / 8 male) was evaluated
      and compared with 22 age-matched healthy subjects (age 50.5 + 9.4 years, 13
      female / 9 male) for this purposes. Eurofit Test Battery for Adults is composed
      of aerobic fitness, musculoskeletal fitness, motor fitness, and anthropometry
      components. Aerobic fitness, which was assessed by six minutes walking distance,
      was lower in the patient group than controls (p < 0.05). Hemodialysis patients
      had lower motor fitness (0.000) and musculoskeletal fitness including vertical
      jump and handgrip tests (0.047, 0.002). Percentage of body fat and skinfold
      thickness values measured from triceps, subscapular, abdominal, and thigh were
      also lower in patient group (p < 0.05). Additionally no complication was seen
      during and/or after the tests. In conclusion, the Eurofit for adults may be
      considered a useful test battery to evaluate the physical fitness and design the
      health-related physical fitness program based on the Eurofit results in this
      population.

PMID- 18067041
TI  - Treatment of hepatitis C in hemodialysis patients with pegylated interferon alpha
      2a as monotherapy.
AB  - BACKGROUND: The high prevalence of hepatitis C virus (HCV) infection in
      hemodialysis patients is of great concern because they have a higher rate of
      mortality than HCV-negative hemodialysis patients. The aim of the study was to
      evaluate the efficacy and safety of pegylated interferon alpha-2a monotherapy in
      hemodialysis patients with chronic HCV infection. METHODS: Fourteen dialysis
      patients with chronic HCV infection were scheduled to receive 135 mug pegylated
      interferon alpha-2a subcutaneously, once a week, after dialysis session for a
      period of 48 weeks. Efficacy and safety were assessed by end of treatment viral
      response, sustained viral response, biochemical response, and adverse events.
      Serum HCV RNA levels were assessed using reverse transcriptase polymerase chain
      reaction (RT-PCR), while HCV genotype was analyzed by RT-PCR followed by
      hybridization of amplified products. RESULTS: Of the 14 patients enrolled in the
      study, 9 completed treatment. Eight patients (57%) had undetectable levels of HCV
      RNA at the end of treatment, while one patient remained positive. Two (14.3%)
      patients were discontinued because of insufficient therapeutic response. Three
      patients (21.34%) did not finish treatment because serious adverse events
      occurred: one patient with bronchopneumonia and one with pericarditis were
      discontinued from treatment, while one patient died due to cerebral hemorrhage.
      Sustained viral response was present in 36% of the patients (5/8 patients) at the
      end of the follow up period. Biochemical response with normalization of serum ALT
      levels during treatment was observed in all treated patients (83 +/- 20.1 U/L at
      baseline vs. 23.4 +/- 4.6 U/L at week 48). The most common adverse events were
      flu-like syndrome, myalgia, arthralgia, and pancytopenia. Most of the adverse
      events were manageable. The serious adverse events were believed to be unrelated
      to the therapy, but rather to the co-morbidities of the hemodialysis patients.
      CONCLUSIONS: Pegylated interferon alpha-2a treatment was effective in a
      considerable proportion of the treated hemodialysis patients with hepatitis C,
      and it was reasonably safe to use.

PMID- 18067042
TI  - Association between decreased kidney function and endotoxin receptor CD14 C-159T
      polymorphism among Japanese health check-up examinees.
AB  - BACKGROUND: A recently identified promoter polymorphism of the endotoxin receptor
      (CD14 C-159T) was shown to be associated with atherosclerotic diseases such as
      myocardial infarction. This study was conducted to determine whether this
      polymorphism is associated with decreased kidney function. METHODS: A total of
      281 male and 522 female health check-up examinees, aged 39-88 years, were
      genotyped for CD14 C-159T. The glomerular filtration rate (GFR) was estimated by
      the Modification of Diet in Renal Disease (MDRD) Study equation. Estimated GFR
      (eGFR) and the proportion of subjects with mildly decreased eGFR (eGFR under 90
      mL/min/1.73 m(2)) were compared among the genotypes. RESULTS: Subjects carrying
      the T allele showed decreased age- and sex-adjusted eGFR compared with those with
      CC genotype (101+/-22 vs. 105+/-23 mL/min/1.73 m(2); mean+/-SD, p = 0.012). The
      proportion of subjects with mildly decreased eGFR was higher in T allele carriers
      (34.2% for TT+CT and 26.3% for CC genotype, p = 0.041), but not statistically
      significant when adjusted for age and sex (odds ratio [OR] 1.41, 95% CI 0.97
      2.05, p = 0.076). In subjects under 65 years, T allele carriers had a
      significantly increased risk for mildly decreased eGFR (27.1% for TT+CT and 18.0%
      for CC; age- and sex-adjusted OR 1.82, 95% CI 1.06-3.12, p = 0.030). CONCLUSION:
      CD14-159T allele was associated with decreased eGFR compared with CC genotype,
      and with a higher prevalence of mildly decreased eGFR in younger subjects under
      65.

PMID- 18067043
TI  - Comparison of bacterial isolates cultured from hemodialysis patients and other
      patients with diabetic foot and their antimicrobial resistance.
AB  - The aim of this study was to compare microbial findings and their resistance to
      antibiotics between hemodialysis patients and patients without end-stage renal
      failure with diabetic foot infections. An 18-month-long descriptive study
      analyzed bacterial isolates obtained from 32 hemodialysis (HD) patients with
      diabetic foot infection in an Antakya hemodialysis center and 65 patients with
      diabetic foot infection admitted to the Education and Research Hospital of
      Mustafa Kemal University, Turkey. No significant difference in the mean number of
      pathogens per patient was found between the dialysis patients and other patients
      (2.3 vs. 2.1, respectively) (p > 0.05). While the occurrence of gram-positive
      bacteria in the HD patients was found to be 59.0%, this rate in the other
      patients was 53.1% (p > 0.05). While most frequent bacterial species isolated in
      the HD patients were S. aureus (22.9%), followed by coagulase-negative
      Staphylococcus spp. (CNS) (19.7%), the microorganisms in the other patients were
      found as CNS (20.7%), followed S. aureus (18.0%). The data recommend that
      antibiotic therapy in HD patients with diabetic foot infection should be more
      closely guided by culture findings and antimicrobial susceptibility results.

PMID- 18067044
TI  - Ambulatory blood pressure and endothelial dysfunction in patients with autosomal
      dominant polycystic kidney disease.
AB  - Cardiovascular problems are a major cause of morbidity and mortality in patients
      with autosomal dominant polycystic kidney disease (ADPKD). Endothelial
      dysfunction (ED), which is an early manifestation of vascular injury, has been
      shown in patients with ADPKD. However, the association between ambulatory blood
      pressure and ED has not been investigated in these patients. Forty-one patients
      with ADPKD having well-preserved renal function were included in the study.
      Ambulatory blood pressure monitoring was performed in all patients. Patients were
      divided into dipper and non-dipper groups. Endothelial function of the brachial
      artery was evaluated by using high-resolution vascular ultrasound. Endothelial
      dependent dilatation was expressed as the percentage change in the brachial
      artery diameter from baseline to reactive hyperemia. The mean 24-hour systolic
      blood pressure was similar in both groups (125.5 +/- 10.7 mmHg in dippers and
      121.2 +/- 14.3 in non-dippers, p > 0.05). There was also no significant
      difference between the mean 24-hour diastolic blood pressures in both groups
      (82.3 +/- 9.6 mmHg in dippers and 77.1 +/- 8.6 mmHg in non-dippers, p > 0.05).
      The nocturnal fall rate in systolic blood pressure was 11.1 +/- 1.2% in dippers
      and 0.98 +/- 0.9% in non-dippers (p = 0.001). The nocturnal fall rate in
      diastolic blood pressure was 14.0 +/- 0.9% in dippers and 3.8 +/- 0.8% in non
      dippers (p = 0.001). Endothelial-dependent dilatation was significantly higher in
      dippers compared to non-dippers (6.22 +/- 4.14% versus 3.57 +/- 2.52%, p =
      0.025). Non-dipper patients with ADPKD show significant ED, which has an
      important impact on cardiovascular morbidity and mortality.

PMID- 18067045
TI  - Acute effect of furosemide on glomerular filtration rate in diastolic
      dysfunction.
AB  - We sought to evaluate the acute effect of furosemide on glomerular filtration
      rate (GFR) in subjects with diastolic dysfunction. An equal number of subjects
      with documented diastolic dysfunction (DD) and healthy volunteers (controls) were
      enrolled and underwent a baseline GFR measurement via plasma clearance of
      technetium-99m-diethylenetriaminepentaacetic acid. Within three to seven days of
      the baseline, study subjects were scheduled for a second GFR study, which was
      performed immediately after administration of furosemide (20 mg orally and 20 mg
      intravenously). There were eight healthy volunteers (8 males with a mean age 42
      +/- 7.8 years; 6 white, 2 Asian) and eight subjects with diastolic dysfunction (7
      males, 1 female, with a mean age 64.5 +/- 9.3 years; 7 whites, 1 African
      American). There was a significant post-furosemide decline in GFR in the healthy
      volunteers, baseline vs. post-furosemide 131.6 +/- 19.8 vs. 117 +/- 18.2 mL/min,
      respectively (p = 0.03), and the patients with DD, baseline vs. post-furosemide
      117.5 +/- 22.3 vs. 92 +/- 21.7 mL/min, respectively (p = 0.0002). A strong trend
      was detected, though not statistically significant, of greater GFR decline in
      subjects with DD compared to the healthy volunteers, 25.5 +/- 9.9 vs. 14.6 +/-
      15.6 mL/min, respectively (p = 0.12). To conclude, acute administration of
      furosemide might potentially cause a greater decline in GFR in subjects with
      diastolic dysfunction.

PMID- 18067046
TI  - Outcomes of acute renal failure patients requiring intermittent hemodialysis.
AB  - The published studies on the prognosis of patients requiring intermittent
      hemodialysis (IHD) are scarce and have some conflicts. In this study, we
      retrospectively analyzed our data on ARF patients who were treated with IHD. A
      total of 192 (female: 85, 44.3%; male: 107, 55.7%) patients were included in the
      study. The mean age was 56.3 +/- 17.1 years. In all, 48.9% of the patients were
      older than 60 years. The mean number of IHD sessions was 7.8 +/- 8.0 per patient;
      12.4% was due to prerenal causes, 76.8% was due to intrarenal causes, and 10.8%
      was due to postrenal causes. The leading indication of the IHD was uremic
      symptoms (46.8%). With the exclusion of hypertension, 72.4% of the patients had
      at least one systemic comorbidity. After treatment, 75.5% of the patients
      recovered, in contrast to 9.4% of patients who were transferred to chronic renal
      replacement programs and 15.1% who died during IHD period. Pre-dialytic serum
      creatinine (p = 0.003) and albumin levels (p = 0.016), total IHD session number
      per patient (p = 0.003), and age (p = 0.034) were the parameters that were
      related to high mortality in statistical analysis. Mortality was higher if the
      leading indication of IHD was biochemical disturbances (p = 0.013). Diabetes
      mellitus did not influence mortality. Consequently, predialytic serum creatinine
      and albumin levels may be very important predictors of mortality. Patients in
      high-risk groups (older age, female sex, and low pre-dialytic creatinine and
      albumin levels) should be considered to be treated with slow continuous renal
      replacement methods.

PMID- 18067047
TI  - A cohort study of subjective global assessment and mortality in Taiwanese
      hemodialysis patients.
AB  - Many patients with end-stage renal disease are malnourished, and cross-sectional
      studies have shown that markers of malnutrition may predict death. In this study,
      we investigated the possible association of Subjective Global Assessment and
      mortality in a small cohort of Taiwanese hemodialysis patients. Fifty
      hemodialysis patients at a hemodialysis center in eastern Taiwan were enrolled in
      June 2002. Height and weight were used to determine the body mass index.
      Bioelectrical impedance analysis of body fat mass was performed before and after
      a mid-week dialysis session. Biochemical indexes of the nutritional status
      included serum albumin, creatinine, transferrin, cholesterol, and the normalized
      protein catabolic rate. Mortality data during 42 months after enrollment were
      obtained. Twenty-six hemodialysis patients were classified as well-nourished and
      twenty-four as malnourished based on Subjective Global Assessment. Decreased body
      mass index (p = 0.006), increased body fat mass (p = 0.019 before hemodialysis; p
      = 0.007 after hemodialysis), decreased serum albumin (p = 0.011), and decreased
      serum creatinine (p = 0.006) were significantly higher in the malnourished group.
      Older age (p = 0.042), decreased serum albumin (p = 0.028), decreased serum
      transferrin (p = 0.041), and malnourishment (p = 0.004) were significantly higher
      in the mortality group. Multivariate forward stepwise linear regression analysis
      of mortality and nutrition profiles show that Subjective Global Assessment is the
      independent predictor of mortality (R(2) = 0.20). Malnourished hemodialysis
      patients had a higher mortality rate than well-nourished hemodialysis patients in
      Taiwan. Subjective Global Assessment of the nutritional status appears to be a
      simple tool for assessing the nutritional status of hemodialysis patients in long
      term care. This assessment tool is also beneficial for hemodialysis patients who
      are at a greater risk of nutritional-associated mortality.

PMID- 18067048
TI  - Calcium channels blockers and progression of kidney disease.
AB  - We aimed to compare regimens including calcium channel blockers (CCBs) to non
      CCBs agents such as angiotensin-converting enzyme inhibitors (ACEIs) and/or
      angiotensin receptor blockers (ARBs) regarding progression in nondiabetic chronic
      kidney disease (CKD). There was no difference in reaching serum creatinine
      concentration (Cr) to more than 7 mg/dL and/or commencing dialysis. The CCB group
      compared to non-CCBs displayed a higher mean Cr (as well as a higher rate of
      increase) and proteinuria. Medication with CCBs and younger age were associated
      with adverse renal function outcome. It is concluded that CCBs are less effective
      than ACEIs or ARBs on preserving renal function and ameliorating proteinuria in
      nondiabetic CKD.

PMID- 18067049
TI  - A biomarker for detecting early tubulointerstitial disease and ischemia in
      glomerulonephropathy.
AB  - Present diagnostic tests such as serum creatinine determination and creatinine
      clearance are unable to reflect early tubulointerstitial disease. Because a
      kidney biopsy cannot be performed in every single patient, tubular epithelial
      function (namely, the fractional excretion of magnesium; FE Mg) that correlates
      directly with the degree of tubulointerstitial fibrosis would serve this purpose.
      FE Mg is normal in acute post-streptococcal glomerulonephritis and mesangial
      proliferative nephrosis with intact tubulointerstitial structure, and is
      abnormally elevated in nephrosis with focal segmental glomerulosclerosis (FSGS)
      and in chronic kidney diseases in which kidney biopsies have been obtained. FE Mg
      is useful in the screening of tubulointerstitial disease in patients when
      indication for kidney biopsy in not fulfilled, such as diabetic patients or
      patients with microscopic proteinuria, hematuria, and hypertension. Altered FE Mg
      is usually associated with a reduction in peritubular capillary flow. There is a
      linear correlation between FE Mg and peritubular capillary flow, which supports
      the chronic ischemic injury inducing altered tubular function and
      tubulointerstitial fibrosis.

PMID- 18067050
TI  - The effect of renal replacement therapies on serum gastrointestinal system
      hormones.
AB  - BACKGROUND: The kidney is a major site for the inactivation, degradation, and
      clearance of a variety of peptide hormones. It has been shown that the uremia
      increases or decreases gastrointestinal system (GIS) hormones. Moreover, studies
      investigating the serum GIS hormones levels in chronic renal failure (CRF) were
      conducted mainly in a particular period of the renal replacement therapy, and the
      changes caused by continuous ambulatory peritoneal dialysis (CAPD) and
      hemodialysis (HD) could not be fully demonstrated. In this study, we investigated
      the effect of CAPD and HD on serum GIS hormones (amylase, lipase, trypsinogen,
      and gastrin) levels in CRF patients who were diagnosed for the first time.
      METHODS: Serum amylase, lipase, trypsinogen, and gastrin levels were measured in
      36 patients who were just diagnosed with CRF, 22 patients with CAPD and 14
      patients with HD. GIS hormones of these patients were measured before treatment
      and three months from the beginning of CAPD and HD treatment. As the control
      group, 20 normal healthy cases with well-matched age and gender were used.
      RESULTS: The mean serum amylase, lipase, secretin, and gastrin levels were found
      meaningfully decreased according to the beginning values at third months of the
      CAPD and HD treatment. However, they were higher than control group. CONCLUSION:
      In patients receiving CAPD or HD as renal replacement therapy, GIS hormone levels
      were found to be lower, albeit higher than the healthy control group.

PMID- 18067051
TI  - 1-Methylhydantoin cytotoxicity on renal proximal tubular cells in vitro.
AB  - 1-Methylhydantoin is produced by bacterial creatinine deaminase in the intestinal
      tract of uremic patients and retaken up into the body. The present study was
      designed to explore the toxic effect of 1-methylhydantoin on renal proximal
      tubular cells in vitro. HK-2 (Human renal proximal tubular cell line) was used as
      the subject. The cell viability was assessed by MTT assay. The cytotoxicity of 1
      methylhydantoin to HK-2 was determined by NAG release test. Apoptosis of cultured
      HK-2 was determined by flow cytometry (light scatter and propidium iodide/annexin
      V-FITC fluorescence) and by nuclear staining with Hoechst 33258. Cells were
      exposed to 1-methylhydantoin (0.25mMol/L, 0.5mMol/L, or 1mMol/L), or creatinine
      (1mMol/L) for 24 h. 1-methylhydantoin induced a significant (p < 0.01) dose
      dependent loss of cell viability. 1-methylhydantoin-treated HK-2 displayed
      characteristic microscopic features of apoptosis: reduced cell size, nuclear
      disintegration, and membrane bleb formation. FACS analysis demonstrated that 1
      methylhydantoin induced apoptosis as well as cell changes consistent with
      necrosis. The proportion of cells with nuclear changes of apoptosis, identified
      by flow cytometry, increased significantly (p < 0.01) after 1-methylhydantoin
      (0.5mMol/L ) for 24 h. The results of the present study clearly demonstrate that
      both 1-methylhydantoin and creatinine are toxic for proximal tubular cells but
      that the damage resulting from the 1-methylhydantoin is more severe.

PMID- 18067054
TI  - Gold nanoparticle as an alternative tool for urine microalbumin test: the first
      world report.
AB  - Urine microalbuminuria is a common indicator for occult preclinical nephropathy.
      At present, urine microalbumin test is routinely performed by clinical chemistry
      test. Here, the authors used the advanced nanomedicine technique for modification
      of the urine microalbumin test. MATERIALS AND METHODS: The preparation of gold
      nanoparticle solution in this study was according to the standard method reported
      by Frenkel et al. The author performed an experiment on both microalbumin
      positive and negative urine samples. First, the mixture between equal amount (500
      microliter) of gold nanoparticle solution and urine sample was prepared. RESULTS:
      The microalbumin-positive mixture becomes purple, while the pregnancy-negative
      mixture becomes gray. CONCLUSION: This application can help the diagnosis of
      microalbumin and can be the alternative way for this urine microalbumin test.
      This is the first world report on this application.

PMID- 18067052
TI  - Tubular and glomerular L-arginine transport (uptake and transporters) and the
      nitric oxide synthases in ischemic acute renal failure (iARF) in streptozotocin
      induced diabetic rats (STZ-DM).
AB  - BACKGROUND: L-arginine or its metabolites may be important pathogenetic factors
      in ischemic acute renal failure (iARF) in rats. It was found that the L-arginine
      nitric oxide synthase-nitric oxide system plays an important role in the renal
      hemodynamic alterations in the early stages of diabetes. The iARF in diabetic
      rats is much more severe than the normal rats exposed to a same ischemia time.
      The purpose of the present study was to evaluated L-arginine uptake and its
      transporters and nitric oxide synthase isoform expression in tubuli and glomeruli
      of STZ-induced diabetic rats with iARF. METHODS: iARF was induced by right
      nephrectomy and left renal artery clamping for 60 min followed by a 60 min reflow
      period. iARF was induced in STZ diabetes rats two weeks after intraperitoneal
      streptozotocin (60 mg/kg body weight) and in normal control rats. L-arginine
      uptake, L-arginine transporters (CAT1 and CAT2) and nitric oxide synthases (iNOS,
      eNOS, and bNOS) were determined by RT-PCR) in both glomeruli and tubuli
      preparations. RESULTS: The STZ diabetic rats compared with the non diabetic
      normal rats have a higher glomerular L-arginine uptake, higher iNOS mRNA, lower
      eNOS mRNA, and lower tubular CAT1 mRNA, eNOS mRNA, and bNOS mRNA. The diabetic
      iARF after one hour of reperfusion had lower glomerular L-arginine uptake, lower
      CAT1 mRNA, lower eNOS mRNA, lower bNOS, and higher tubular iNOS mRNA compared
      with iARF in normal rats. CONCLUSIONS: Our findings suggest a prolonged and more
      severe post-glomerular vasoconstriction very early after the reflow in the iARF
      of STZ diabetic rats compared with the iARF in the normal control rats. That may
      be a plausible explanation to the very significant decline in GFR and tubular
      necrosis that characterize the iARF in diabetic rats.

PMID- 18067053
TI  - Glibenclamide effects on renal function and histology after acute hemorrhage in
      rats under sevoflurane anesthesia.
AB  - INTRODUCTION: Hypovolemia from hemorrhage evokes protective compensatory
      reactions, such as the renin-angiotensin system, which interferes in the
      clearance function and can lead to ischemia. This study was designed to evaluate
      the effects of glibenclamide, a K(+)(ATP) channel blocker, on renal function and
      histology in rats in a state of hemorrhagic shock under sevoflurane anesthesia.
      MATERIAL AND METHODS: Twenty Wistar rats were randomized into two groups of 10
      animals each (G1 and G2), only one of which (G2) received intravenous
      glibenclamide (1 microg.g(-1)), 60 min before bleeding was begun. Both groups
      were anesthetized with sevoflurane and kept on spontaneous respiration with
      oxygen-air, while being bled of 30% of volemia in three stages with 10 min
      intervals. There was an evaluation of renal function - sodium para-aminohippurate
      and iothalamate clearances, filtration fraction, renal blood flow, renal vascular
      resistance - and renal histology. Renal function attributes were evaluated at
      three moments: M1 and M2, coinciding with the first and third stages of bleeding;
      and M3, 30 min after M2, when the animals were subjected to bilateral nephrectomy
      before being sacrificed. RESULTS: Significant differences were found in para
      aminohippurate clearance, G1 < G2, and higher renal vascular resistance values
      were observed in G1. Histological examination showed the greater vulnerability of
      kidneys exposed to sevoflurane alone (G1) with higher scores of vascular and
      tubular dilatation. There were vascular congestion and tubular vacuolization only
      in G1. Necrosis and signs of tubular regeneration did not differ in both groups.
      CONCLUSION: Treatment with glibenclamide attenuated acutely the renal
      histological changes after hemorrhage in rats under sevoflurane anesthesia.

PMID- 18067055
TI  - End-stage renal disease following carboplatin chemotherapy for a nasopharyngeal
      carcinoma.
AB  - Renal failure secondary to carboplatin therapy is due to acute tubular necrosis
      and is usually reversible. However, acute renal failure with rapid progression to
      end-stage renal disease is an exceedingly rare complication of carboplatin
      therapy. The authors report a case of definitive renal failure secondary to
      carboplatin chemotherapy for a nasopharyngeal carcinoma. The mechanisms that give
      rise to the chronic nephropathy are discussed.

PMID- 18067056
TI  - Acute renal failure during pregnancy secondary to spontaneous perirenal hematoma.
AB  - A 32-year-old pregnant female presented with right flank pain, hematuria, and ARF
      at 25 weeks of gestation. Imaging studies demonstrated right perinephric
      hematoma, which compressed the inferior vena cava. ARF improved with expectant
      care as the hematoma gradually resolved.

PMID- 18067057
TI  - Are antibiotic drugs well prescribed in case of renal insufficiency? A
      retrospective study.
AB  - Renal insufficiency (RI) is a major complication in hospitalized patients. We aim
      to determinate if the severity of RI is considered for antibiotic prescriptions.
      A 10-month retrospective study including all in-patients of an orthopedic surgery
      department, based on the analysis of antibiotic prescriptions of patients with
      RI, was set up as follows: identification of patients with RI estimated with
      Cockcroft formula, classification by severity stage, and analysis of antibiotic
      prescriptions to be adapted to RI. About 10% of patients had RI. Among them, 54
      (32%) received antibiotics (on average, 1.75 drugs per patient). Sixteen (17%) of
      antibiotic prescriptions required either dose adaptation or therapeutic drug
      monitoring. In all, only four prescriptions were adapted to renal function. In
      other cases, antibiotics were prescribed according to protocols for patients with
      normal renal function. Moreover, therapeutic drug monitoring was only performed
      for half of required cases and then showed values > ULN three times out of four.
      Creatinine clearance (CrCl) has been calculated for half of patients with RI. In
      practice, dosage adjustment of antibiotics is done only for patients with severe
      RI. Within the framework of the introduction of an electronic prescribing
      technology and medication order pharmaceutical review procedures, CrCl is now
      systematically calculated and then taken into account by both prescribers and
      clinical pharmacists.

PMID- 18067059
TI  - Acute renal failure after initiation of tenofovir disoproxil fumarate.
AB  - Despite initial evidence suggesting a relatively benign safety profile, several
      subsequent case reports have detailed nephrotoxicity in patients using tenofovir
      disoproxil fumarate for the treatment of HIV. We report a case of rapid renal
      failure that developed into an HIV-naive patient initiated on an antiretroviral
      regimen that included tenofovir.

PMID- 18067058
TI  - Biopsy proven acute tubular necrosis associated with vancomycin in a child: case
      report and literature review.
AB  - Vancomycin-related nephrotoxicity typically manifests as acute tubulointerstitial
      nephritis. The drug does appear, however, to increase the nephrotoxicity of
      concurrently administered aminoglycosides. The extent of direct tubular toxicity
      attributable to vancomycin, especially in the absence of aminoglycoside
      treatment, does not appear to have been previously described. We report a case of
      biopsy-proven acute tubular necrosis secondary to vancomycin toxicity in a 13
      year-old boy where there was no likely alternate explanation for toxic or
      ischemic injury. No hemodialysis was required, and the patient made a full
      recovery with subsequently regained renal function.

PMID- 18067061
TI  - An aryldihydronaphthalene lignan with a novel type of ring system and further new
      lignans from linum perenne L.
AB  - From the dichloromethane extract of aerial parts of Linum perenne L. (Linaceae),
      in addition to three lignans of the arylnaphthalene type (justicidin B,
      isojusticidin B and retrohelioxanthin), we isolated four lignans of the
      aryldihydronaphthalene type. The major constituent contains a novel type of ring
      closure, formed by additional cyclisation between rings A and D of the
      aryldihydronaphthalene skeleton via an oxymethylene bridge, yielding a novel 2,8
      dihydro-3 H-benzo[ E]naphtho[1,8- BC]oxepine ring system hitherto unreported for
      a lignan or any other natural product. We named this novel unusual lignan
      linoxepin. In addition, three further aryldihydronaphthalenes (one new and two
      known) were isolated. The absolute stereochemistry at C-8 of linoxepin and the
      related dihydronaphthalene lignans was established as R on grounds of CD spectra
      which were in good agreement with results of time dependent density functional
      (TDDFT) quantum mechanical simulations. The occurrence of aryldihydronaphthalenes
      in the genus Linum or the Linaceae has not been reported before.

PMID- 18067062
TI  - Gomisin A from Schisandra chinensis induces endothelium-dependent and direct
      relaxation in rat thoracic aorta.
AB  - Schisandra chinensis (SC), a member of the Magnoliaceae family, has been used to
      improve the vascular health for postmenopausal women in Korea. In order to
      provide some scientific rationales for such effectiveness, this study
      investigated the vascular effects of gomisin A (GA) from SC. In the endothelium
      (ED)-intact rings of rat thoracic aorta, GA (1 x 10 (-6) to 3 x 10 (-4) M) caused
      a concentration-dependent relaxation which was markedly attenuated not only by
      removal of ED but also by pretreatment with N(G)-nitro- L-arginine (10 (-4) M) or
      1 H-[1,2,4]oxadiazol[4,3- a]quinoxalin-1-one (3 x 10 (-5) M). Direct measurement
      of nitrite, a metabolite of nitric oxide (NO), confirmed that NO production in
      isolated aorta was increased by GA. In the ED-denuded specimens, the relaxation
      by GA was not abolished but reduced significantly. The relaxation by GA in ED
      denuded aortic rings were clearly inhibited by calyculin A (3 x 10 (-8) M), an
      inhibitor of MLC phosphatase. Furthermore, the phenylephrine-enhanced
      phosphorylation ratio of MLC was significantly attenuated by GA. Based on these
      results, it is suggested that GA induced vascular relaxation by partially
      activating ED-dependent NO pathway, and partially dephosphorylation of MLC.

PMID- 18067063
TI  - Comparative analysis of bioactivities of four Polygonum species.
AB  - Many species of Polygonum are rich in bioactive constituents, which contribute to
      a wide range of medicinal properties. In this study, we assessed the scavenging
      activity against ABTS.+ and hydroxyl radicals, chelating activity against Fe2+,
      xanthine oxidase inhibition, antimicrobial activity, and total contents of
      phenolics and flavonoids in the extracts of leaves and stems or whole plants from
      four medicinal Polygonum species. Total antioxidant capacities and phenolic
      contents of Polygonum capitatum, Polygonum Chinensis, Polygonum cuspidatum, and
      Polygonum multiflorum were 74.60, 53.66, 56.22, and 14.34 mmol trolox/100 g dry
      weight (DW), and 8.69, 4.15, 6.33, and 1.27 g gallic acid/100 g DW, respectively,
      significantly higher than those of five dietary vegetables, fruits and spices
      (spring onion, broccoli, orange, carrot, and ginger). Major bioactive
      constituents in the tested plant extracts were also investigated using LC-MS.
      They were mainly phenolic compounds, e. g., flavonoids, phenolic acids and their
      derivatives, tannins, stilbenes, and anthraquinones. This study shows that, in
      addition to their roots, the leaves and stems of P. cuspidatum and P. capitatum
      also exhibit potent antioxidant properties and are a potential resource of
      natural bioactive antioxidants.

PMID- 18067064
TI  - Development and validation of an HPLC method for quality control of Pueraria
      lobata flower.
AB  - Pueraria lobata, also known as Kudzu (Japan) or Ge (China), is a medicinal plant
      widely used in Oriental traditional medicine. In this study the development,
      optimization and validation of an HPLC ethod for quality control of Pueraria
      flower plant material is presented. By means of this analytical method the three
      major compounds, i. e., the isoflavones tectorigenin 7- O-[beta- D-xylopyranosyl
      (1 - 6)-beta- D-glucopyranoside], tectorigenin 7- O-beta- D-glucopyranoside and
      tectorigenin, were quantified, using the isoflavones genistin and genistein as
      external standards. The extraction procedure, the extraction solvent, the
      extraction yields and the HPLC conditions were evaluated and optimized. The
      samples were analyzed on an RP C18 column, and eluted with a binary system
      consisting of water and methanol using a linear gradient; detection was at 262
      nm. Tectorigenin used in the recovery experiments was isolated and purified in
      the laboratory. The final method was fully validated according to the ICH
      guidelines in terms of linearity, precision and accuracy. The validation data
      showed that the precision, (RSD% (betweendays) of 3.1, 2.84 and 1.77 for the
      three major compounds, respectively), and the accuracy (recovery of 104.2 %) were
      acceptable. These validation results demonstrate the suitability of the method
      for the quality control of this crude drug.

PMID- 18067065
TI  - Frequency and severity of ileal adenomas in familial adenomatous polyposis after
      colectomy.
AB  - BACKGROUND AND STUDY AIMS: The high cumulative risk of colorectal cancer in
      patients with familial adenomatous polyposis (FAP) justifies prophylactic
      colectomy with either ileorectal (IRA) or ileal-pouch-anal anastomosis (IPAA).
      Our aim was to evaluate retrospectively the frequency of and time interval to
      adenoma development in the ileal mucosa of patients with both types of surgery.
      PATIENTS AND METHODS: Retrospective study of 44 FAP patients with IRA (n = 21)
      and IPAA (n = 23). All patients were followed with a standardized procedure
      including chromoscopy and biopsies of visible polyps. In patients with IRA,
      specific attention was paid to the ileal mucosa above the anastomosis. RESULTS:
      In the IPAA group, 18/23 patients (78 %) presented with visible polyps
      [histology: 16 (70 %) had adenoma with low-grade dysplasia; 1 (4 %) had adenoma
      with high-grade dysplasia; 1 had normal mucosa]. The mean interval between
      colectomy and the diagnosis of adenoma was 4.7 +/- 3.3 years. In the IRA group,
      16/21 patients (77 %) presented visible polyps in the ileal mucosa [adenoma with
      low-grade dysplasia in 8 patients (38 %), with high-grade dysplasia in 2 (10 %),
      and lymphoid nodular hyperplasia in 6]. The mean interval between colectomy and
      adenoma diagnosis was significantly shorter in the IPAA than in the IRA group
      (4.76 +/- 3.3 vs. 16.4 +/- 8.5 years, P< 0.0001). CONCLUSION: Our results show a
      high frequency of adenomas in the ileal mucosa of patients with IPAA and IRA (74
      % and 48 % respectively), with evolution into high-grade dysplasia in 6.7 % of
      cases.

PMID- 18067066
TI  - Endoscopic ultrasound-guided fine-needle aspiration for diagnosis of solid
      pseudopapillary tumors of the pancreas: a multicenter experience.
AB  - BACKGROUND AND STUDY AIMS: Solid pseudopapillary tumors of the pancreas are rare,
      low-grade, epithelial neoplasms that are usually discovered incidentally in young
      women. Distinguishing solid pseudopapillary tumors from other pancreatic tumors,
      especially pancreatic endocrine tumors, can be challenging. The role of
      endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in this context
      remains unclear. The purpose of this study was to describe the endoscopic
      ultrasound features of solid pseudopapillary tumors and the role of EUS-FNA in
      the preoperative diagnosis of these tumors. PATIENTS AND METHODS: Patients from
      five tertiary referral centers with surgically confirmed solid pseudopapillary
      tumors who had undergone preoperative EUS-FNA were included. The endoscopic
      ultrasound findings, cytologic descriptions, immunostaining results, operative
      records, surgical pathology, and results of the most recent clinical follow-up
      were reviewed. RESULTS: A total of 28 patients were identified (four men [14 %],
      24 women [86 %], mean age +/- standard deviation [SD] 35 +/- 10 years). Solid
      pseudopapillary tumors had been found as incidental findings on cross-sectional
      imaging in 50 % of cases. The mean tumor size +/- SD was 42 +/- 19.5 mm and the
      majority were located in the pancreatic body and tail. The endoscopic ultrasound
      report described a well-defined, echo-poor mass in 86 %; the tumors were solid in
      14 patients (50 %), mixed solid and cystic in 11 patients (39 %), and cystic in
      three patients (11 %). A preoperative diagnosis of solid pseudopapillary tumor
      was made in 21 patients (75 %) on the basis of EUS-FNA cytology. Surgical
      resection was performed in all cases. Laparoscopic resection was performed in
      eight of these patients (29 %). CONCLUSIONS: A solid pseudopapillary tumor should
      be included in the differential diagnosis of any well-demarcated, echo-poor,
      solid or mixed solid/cystic pancreatic lesion seen during endoscopic ultrasound,
      particularly in young women. The diagnostic accuracy of EUS-FNA for solid
      pseudopapillary tumors was 75 % in this study. A definitive preoperative
      diagnosis can guide the surgical approach in selected cases.

PMID- 18067067
TI  - Capsule endoscopy and cardiac pacemakers: investigation for possible
      interference.
AB  - BACKGROUND AND STUDY AIMS: The diagnostic benefit of capsule endoscopy in
      suspected small-bowel disease is high and seems to be superior to that with
      conventional methods and scintigraphy. Because of the limited clinical experience
      in patients with cardiac pacemakers and other implanted electrical devices, it is
      recommended that capsule endoscopy should not be used in such cases. We
      investigated the potential for capsule endoscopy to interfere with cardiac
      pacemakers in vitro. MATERIAL AND METHODS: 21 different pacemakers and leads were
      positioned in a 0.9 % saline solution in a tank. Pin jacks were placed that were
      in contact with the solution. The pacemaker impulse was recorded and an
      inhibiting signal could be coupled in. The capsules (Given Imaging and Olympus)
      were placed in different positions relative to the cardiac pacemaker and finally
      placed on the case of the pacemaker, for 1 minute in each site. The functioning
      of the pacemaker was observed continuously. The effect on the pacemaker was noted
      particularly as inhibition, synchronization, or no effect. The pacemaker was then
      inhibited using a standard test signal. RESULTS: There was no interference
      between the video capsule and the cardiac pacemakers in our experiment in spite
      of the close proximity of the two devices. CONCLUSION: The clinical use of
      capsule endoscopy is unproblematic in patients with cardiac pacemakers.

PMID- 18067068
TI  - Primary follicular lymphoma of the gastrointestinal tract: a retrospective case
      series.

PMID- 18067069
TI  - [Types and frequencies of variants in Amelogenin gene in Chinese population].
AB  - OBJECTIVE: To investigate the types and frequencies of variants in Amelogenin
      gene in Chinese population and to explore the mutations' influence to the sex
      test. METHODS: The Amelogenin gene of 8850 unrelated Chinese individuals was
      typed with PowerPlex 16 system. The samples with abnormal typing results were
      calculated directly, validated with different primer sets, Y-STR typing and
      sequencing. RESULTS: Two samples with X chromosomal Amelogenin (AMELX) allelic
      dropout and 2 samples with Y chromosomal Amelogenin (AMELY) allelic dropout were
      observed in male individuals, the total rate of mutation was 0.045% and the rate
      in the male was 0.085%. Two types of point mutation which may result in null
      allele were observed in the primer binding region of the plostq AMELX alleles,
      and the mutation rate in the male was 0.042%. The mutation rate of AMELY allele
      was also 0.042%. One sample failed to amplify 10 Y-STR loci out of 12 loci, which
      could be speculated that large interstitial deletion of the Y chromosome
      encompassing the AMELY and other Y-STR loci occurred. CONCLUSION: AMELX or AMELY
      allelic dropout may occur due to the mutation of Amelogenin gene, which may
      interfere with the sex test and induce wrong gender identification.

PMID- 18067070
TI  - [Genetic analysis of a Chinese pedigree with split hand and foot malformation].
AB  - OBJECTIVE: To analyze the clinical manefestation and genetic basis of split hand
      and foot malformation (SHFM) in a Chinese pedigree. METHODS: The affected people
      in the family were checked by X-rays. Eighteen patients provided their peripheral
      blood, and the genomic DNA of the samples was extracted. The linkage and
      haplotype analysis were carried out using the microsatellite markers, and the
      limb malformation related gene Dactylin (DAC) including the coding region, exon
      intron boundaries and part of promoter region was sequenced. RESULTS: Most
      members of the family with the disease phenotype showed absence or hypoplasia of
      the index finger, and absence or 3-4 syndactyly of the middle finger. The degree
      of abnormality in feet was severer than that in hands. All phenotypes of the
      patients display the basic characters of SHFM. Since the maximum two point LOD
      score of the D10S192 was 3.50 (theta=0.00), the SHFM in this pedigree can be
      categorized to the SHFM3. The haplotype analysis of recombination events revealed
      the candidate locus to a 21cM region between D10S185 and D10S1693. No mutation
      was found by the sequencing result of DAC gene. CONCLUSION: Through the analysis
      of phenotype of the patients, the typical SHFM disease can be confirmed. The
      linkage and haplotype analysis demonstrated that the 21cM region in 10q23-q26
      locus was the major cause to the disease in this pedigree. The mutation of DAC
      gene can be excluded from cause of SHFM3 phenotype.

PMID- 18067071
TI  - [Study on mechanisms of the expression regulation of interferon-induced gene RIG
      G].
AB  - OBJECTIVE: To investigate the molecular mechanisms of the expression regulation
      of retinoic acidinduced gene G (RIG-G) by interferon alpha (IFNalpha). METHODS:
      RIG-G promoter region was analyzed by bioinformatics. The functional activities
      of RIG-G promoter with or without IFNalpha were detected by luciferase reporter
      assay and electrophoretic mobility shift assay (EMSA). RESULTS: RIG-G promoter
      region contained two well-conserved IFN-stimulated response elements (ISREs).
      Both ISRE I and ISRE II showed their effective binding abilities with signal
      transducer and activator of transcription 1 (STAT1). In HT1080 cells, in contrast
      with the empty plasmid pXP2, pXP2-A reporter construct containing intact ISRE I
      and ISRE II showed a significant higher baseline expression (1741.2 +/- 517.5)
      which could be further enhanced up to three-four folds by IFNalpha (5338.7 +/-
      1226.9, P < 0.05). However, the luciferase activity of pXP2-A as well as its
      IFNalpha inducibility could be abrogated in STAT1-deficient U3A cells (from
      1741.2 +/- 517.5 to 406.1 +/- 103.2, P < 0.05), indicating that the STAT1 protein
      was a prerequisite for the activities of ISRE I and ISRE II. CONCLUSION: ISREs
      present in RIG-G promoter region are molecular basis of IFNalpha induced RIG-G
      expression. RIG-G is a target gene directly regulated by STAT1 protein and should
      play a key role in IFNalpha signaling pathways.

PMID- 18067072
TI  - [A novel mutation in the myocilin gene identified in a Chinese primary open angle
      glaucoma family].
AB  - OBJECTIVE: To determine the possible myocilin molecular genetic defect underlying
      POAG in China and to identify the pathogenic mutation causing the disease.
      METHODS: The majority of 1 branch of a large Chinese POAG family were personally
      examined by two senior ophthalmologists. The diagnoses were made by both doctors
      according to the signs of elevated intraocular pressure, glaucomatous optic
      neuropathy and glaucomatous visual field defect. All coding sequences of the
      myocilin gene plus the flanking sites were amplified by polymerase chain reaction
      (PCR) using genomic DNA from all examined family members followed by sequencing
      of the PCR products. One hundred normal control subjects were screened by single
      strand confirmational polymorphism analysis for the mutation. RESULTS: This
      Chinese pedigree exhibited autosomal dominant mode of inheritance. The onset age
      ranged from 26 to 59 years. A novel disease-causing missense mutation T455K in
      the third exon of the myocilin gene was identified in all affected family
      members, all glaucoma suspects and 4 individuals who have not shown apparently
      signs of glaucoma. None of the subjects without the mutation had glaucoma.
      Affected individuals with the T455K mutation showed variable onset between 26 and
      59 years of age. Filtering surgery was performed on all of 7 affected family
      members. The T455K mutation in myocilin gene was not found in the normal
      controls. A previously reported polymorphism IVS2+35(A to G)was detected in 4
      individuals. CONCLUSION: The novel myocilin sequence alteration T455K that is
      highly associated with the development of glaucoma and locates in a very
      conserved residue is proven to be a disease-causing missence mutation. All
      affected individuals and all POAG suspects in this family are identified to have
      this mutation. The mutation in this family is associated with a phenotype
      characterized by mix-onset open angle glaucoma and associated with a high
      penetrance. It is important for the mutation screening and periodical checkups of
      presymptomatic individuals belonging to the family of a POAG patient with T455K
      mutation.

PMID- 18067073
TI  - [Analysis of complex chromosomal aberrations in patients with myelodysplastic
      syndromes using multiplex fluorescence in situ hybridization combined with whole
      chromosome painting].
AB  - OBJECTIVE: To explore the value of multiplex fluorescence in situ hybridization
      (M-FISH) in combination with whole chromosome painting (WCP) in the detection of
      complex chromosomal aberrations (CCAs) in myelodysplastic syndromes (MDS).
      METHODS: M-FISH was used in seven MDS patients with R-banding CCAs to refine the
      complex chromosomal rearrangements, and to identify cryptic translocations and
      characterization of marker chromosomes. Dual-color WCP procedures were further
      performed in 7 cases to confirm some rearrangements detected by M-FISH. RESULTS:
      M-FISH confirmed all results of R-banding. The composition and origin of 6 kinds
      of marker chromosomes, 9 kinds of chromosomes with additional material
      undetermined and 5 kinds of derivative chromosomes undefined by conventional
      cytogenetics (CC) were defined after M-FISH analysis; four kinds of cryptic
      translocations overlooked by CC were found on derivative chromosomes and
      previously normal appearing chromosomes. In addition, M-FISH revealed some
      nonrandom aberrations: aberrations involving chromosome 17 and -5/5q- were the
      two most frequent aberrations. Some misclassified and missed chromosomal
      aberrations by M-FISH were corrected by WCP. CONCLUSION: M-FISH is a powerful
      molecular cytogenetic tool in clarification of CCAs. Complementary WCP helps us
      to identify misclassified and missed chromosomal aberrations by M-FISH. CC in
      combination with molecular cytogenetic techniques, such as M-FISH and WCP, can
      unravel complex chromosomal aberrations more precisely.

PMID- 18067074
TI  - [Study on the germline mutation of MSH6 gene in Chinese hereditary nonpolyposis
      colorectal cancer pedigrees using PCR based sequencing].
AB  - OBJECTIVE: To detect the germline mutation of mismatch repair gene (MSH6) in
      hereditary nonpolyposis colorectal cancer (HNPCC) kindreds fulfilling different
      clinical criteria. METHODS: The germline mutations of MSH6 gene were detected by
      PCR based DNA sequencing in 39 unrelated HNPCC probands fulfilling different
      clinical criteria in which MSH2 and MLH1 mutations were excluded. The exons with
      missense mutations were analyzed using PCR sequencing in the germline genomic DNA
      of 137 healthy persons. The expression of MSH6 protein was detected by Envision
      immunohistochemistry staining in the tumor tissues of the mutational probands.
      RESULTS: Six germline mutations of MSH6 gene were detected in 39 probands of
      Chinese HNPCC kindreds, and the mutations distributed in the exon 4, 6, 9 and 10.
      Four out of six mutations were missense mutation, one was nonsense mutation and
      the remaining one was insertion mutation in splice site. The results of sequecing
      for the exons with above four missense mutations in 137 healthy persons' genomic
      DNA showed that 5 of 137 persons had the missense mutation of c.3488 A to T at
      codon 1163 of the 6th exon. The mutational rate was approximately 3.65% (5/137),
      so the mutation could be a single nucleotide polymorphism (SNP). The remaining
      missense mutations were not found in any germline genomic DNA of 137 healthy
      persons. Positive expression of MSH6 protein had been identified in the tumor of
      the SNP proband while the tumors had negative MSH6 protein expression in the rest
      probands of germline mutation MSH6 gene. The types of mutations and their
      potential significance were determined by comparing the following databases:
      http://www.ncbi.nlm.nih.gov/, http://www.ensembl.org/homo-sapies, and
      http://www.insight-group.org. Five out of the six mutations had not been reported
      previously and they were new pathological mutations, the rest one was a new SNP.
      CONCLUSION: Germline mutations of MSH6 gene may play an important role in Chinese
      HNPCC kindreds fulfilling different clinical criteria. It is necessary to analyze
      the germline mutations of MSH6 gene using sequencing to identify HNPCC families
      in the probands in which MSH2 and MLH1 mutation were excluded.

PMID- 18067075
TI  - [EXT1 and EXT2 mutation identified by denaturing high performance liquid
      chromatograph in three families with hereditary multiple exostoses].
AB  - OBJECTIVE: To develop a new denaturing high performance liquid chromatograph
      (DHPLC)-based method to screen patients with EXT gene mutation and to study the
      gene mutation in three families with multiple exostoses. METHODS: All the exons
      of EXT gene, including the intro-exon boundaries, were amplified by PCR. Linkage
      analysis and DHPLC screening were carried out to identify the mutations. DNA
      sequencing was used to confirm the mutations. RESULTS: Two known splice site
      mutations, IVS2+1 G to A and IVS7+1 G to T, and two SNPs have been detected in
      EXT2 or EXT1 gene. CONCLUSION: The transversions of IVS2+1 G to A and IVS7+1 G to
      T in EXT2 gene are suggested to be the disease-causing mutations and the DHPLC is
      a high throughout, sensitive, simple, quick, economical method to screen gene
      mutation in hereditary multiple exostosis.

PMID- 18067076
TI  - [Study on ABO gene polymorphism in Uighur nationality in Xinjiang of China].
AB  - OBJECTIVE: To study the distribution of ABO gene polymorphism in Uighur
      population in Xinjiang area of China. METHODS: DNA was extracted from 160 Uygur
      unrelated donorso blood and PCR-sequence specific primer analysis was performed.
      Some difficult samples were further directly sequenced. RESULTS: Six alleles were
      detected in a population of 160 Uighur individuals, the gene frequencies of which
      were 0.2062(A101), 0.0563(A102), 0.0156(A201),
      0.0031(A205),0.1875(B01),0.5312(O01), respectively. CONCLUSION: The
      characteristics for AB gene structure of Xinjiang Uighur suggests that genetic
      polymorphism is distinguished between Xinjiang Uighur nationality and Chinese Han
      nationality, and both of them have discrepancy and confluent characters.

PMID- 18067077
TI  - [Relationship between polymorphism of urotensin II gene and type 2 diabetes in
      pedigrees].
AB  - OBJECTIVE: To investigate the association between a polymorphism (rs228648) of
      urotensin II (UT-II) gene and type 2 diabetes in pedigrees. METHODS: Patients and
      controls with/without familial history were enrolled in the same place. RESULTS:
      Carriers with AG or AA genotype from pedigrees had higher disease risk than those
      with GG genotype (OR=1.98, 95% CI:1.19-3.29,OR=2.46,95% CI:1.39-4.34), the
      frequency of A allele was higher in the patients from pedigrees than inner
      controls and patients who had no familial history (P=0.01). The frequency of A
      allele was higher in the inner controls than outer ones (P=0.001). The insulin
      resistance index, insulin sensitivity index and pancreatic secretion index of
      inner controls with AG genotype were higher than those with GG genotype (All P <
      0.05). CONCLUSION: This polymorphism of UT-II gene might be a risk to type 2
      diabetes, the insulin function of people from pedigrees is associated with the
      mutation.

PMID- 18067078
TI  - [Construction of haplotype and haplotype block based on tag single nucleotide
      polymorphisms and their applications in association studies].
AB  - Human genome has structures of haplotype and haplotype block which provide
      valuable information on human evolutionary history and may lead to the
      development of more efficient strategies to identify genetic variants that
      increase susceptibility to complex diseases. Haplotype block can be divided into
      discrete blocks of limited haplotype diversity. In each block, a small fraction
      of ptag SNPsq can be used to distinguish a large fraction of the haplotypes.
      These tag SNPs can be potentially useful for construction of haplotype and
      haplotype block, and association studies in complex diseases. There are two
      general classes of methods to construct haplotype and haplotype blocks based on
      genotypes on large pedigrees and statistical algorithms respectively. The author
      evaluate several construction methods to assess the power of different
      association tests with a variety of disease models and block-partitioning
      criteria. The advantages, limitations and applications of each method and the
      application in the association studies are discussed equitably. With the
      completion of the HapMap and development of statistical algorithms for addressing
      haplotype reconstruction, ideas of construction of haplotype based on combination
      of mathematics, physics, and computer science etc will have profound impacts on
      population genetics, location and cloning for susceptible genes in complex
      diseases, and related domain with life science etc.

PMID- 18067079
TI  - [Mutation detection of PKD1 gene in patients with autosomal dominant polycystic
      kidney diseases].
AB  - OBJECTIVE: To detect gene mutation in the patients with autosomal dominant
      polycystic kidney disease (PKD). METHODS: Polymerase chain reaction (PCR)
      denaturing high-performance liquid chromatography (DHPLC) analyses were performed
      in 3o single copy region of PKD 1 gene (PKD1). DNA sequencing were carried out on
      PCR products with abnormal peak shape afterwards. RESULTS: A new nonsense
      mutation (C11901A in exon 42 of PKD1 was identified to cause serine in position
      3897 turning to a stop codon. A missense mutation, C10737T, was detected in exon
      35 which caused threonine in position 3509 turn to methionine. Two kinds of
      samesense mutation, G11824A and C11860T in exon 42, were found in normal control.
      CONCLUSION: PKD1 mutation were detected successfully by PCR-DHPLC. A new nonsense
      mutation, a missense mutation and two polymorphisms are identified in this study.

PMID- 18067080
TI  - [Genotyping and CA4 gene analysis in a Chinese family with retinitis pigmentosa].
AB  - OBJECTIVE: To illuminate pathogenic gene and mutation in a Chinese family with
      autosomal dominant retinitis pigmentosa (adRP). METHODS: Genetic linkage analysis
      was performed on the known genetic loci for adRP with a panel of polymorphic
      markers, and then all exons including exon-intron boundary, 5oUTR and 3oUTR of
      the candidate gene were sequenced directly. RESULTS: Two-point LOD scores were
      negative with all markers tested except D17S701 (Zmax=2.107, theta=0) and
      D17S1604 (Zmax=1.806, theta=0). The disease gene locus was confined to RP17 with
      further genetic linkage and haplotype analysis. Screening all exons including
      exon-intron boundary, 5oUTR and 3oUTR of carbonic anhydrase 4 (CA4) revealed no
      mutation in this family. CONCLUSION: The disease-causing gene of one Chinese
      family with adRP was first mapped to RP17, however no gene mutation of CA4 was
      detected in this family. Maybe there is a complex CA4 gene mutation in this
      family or a new disease-causing gene for this family in this locus, further study
      need to be done.

PMID- 18067081
TI  - [The methylation locus and frequency pattern on p16 INK4a gene promoter CpG in
      epidermis of patients with psoriasis].
AB  - OBJECTIVE: To investigate the CpG methylation locus and frequency pattern on p16
      INK4a gene promoter in epidermis of p16 INK4a methylated patients with psoriasis
      vulgaris. METHODS: The DNA specimens were obtained from epidermal lesion of 50
      plaque psoriatic patients. Methylation specific PCR and DNA sequencing were used
      to detect the frequency and locus of methylation in p16 INK4a gene promoter
      region. RESULTS: Approximately 50% CpG was methylated in p16 INK4a methylated
      patients, methylation was found in specifical locus of p16 INK4a gene promoter.
      CONCLUSION: The distinct methylation pattern is showed on the p16 INK4a gene
      promoter region in patients with psoriasis.

PMID- 18067082
TI  - [Gene screening in five Chinese families with hereditary spastic paraplegia with
      thin corpus callosum].
AB  - OBJECTIVE: To screen all ten genes between D15S971 and D15S1012 in five Chinese
      families with hereditary spastic paraplegia with thin corpus callosum (HSP-TCC).
      METHODS: DNA samples from 5 HSP-TCC families were screened for mutations in
      AK128197, MGC14798, HH114, MEIS2, MGC35118, SPRED1, AK128458, FLJ38426, RASGRP1
      and AK093014 on chromosome 15q13-15 between microsatellites D15S971 and D15S1012
      by polymerase chain reaction, direct sequencing and cosegreagation analysis.
      RESULTS: No disease-causing mutations were found in the 10 genes, but 13
      polymorphisms were identified in which two were novel. CONCLUSION: This study did
      not support the ten genes between D15S971 and D15S1012 were the disease-causing
      genes of the 5 HSP-TCC families.

PMID- 18067083
TI  - [Mutation analysis in families with 21-hydroxylase deficiency].
AB  - OBJECTIVE: To investigate the steroid 21-hydroxylase gene (CYP21) mutations in
      families with 21-hydroxylase deficiency (21-OHD). METHODS: The CYP21 gene
      mutations were detected in four patients with 21-hydroxylase deficiency and their
      relatives. The genomic DNA of the patients was isolated from whole blood.Two
      pairs of primers were used to amplify the CYP21 gene. The amplified PCR products
      were purified by agarose gel and then directly sequenced. RESULTS: Six kinds of
      mutations were found. In the first family, the patient was a compound
      heterozygote carrying four different mutations (cluster E6, Q318X, A391T, P459H)
      onCYP21 gene, three mutations (cluster E6, Q318X, A391T) were on her maternal
      allele, a novel mutation was found:P459H. It located at codon 459 in exon 10 and
      changing a proline (CCC) to a histidine (CAC), and A391T was a rare mutation. In
      the second family, two kinds of mutations were found:cluster E6 and R483W. R483W
      was also a rare mutation. In the third family, the sequencing of the CYP21 gene
      of two patients revealed a homozygous T to A transition in codon 172 leading to
      substitution of isoleucine by asparagine (I172N). CONCLUSION: Six kinds of
      mutations were found in three families with 21-hydroxylase deficiency. Using DNA
      sequencing we have identified a novel mutation (P459H) and two rare mutations
      (A391T, R483W) of the CYP21 gene. Although microconversion events are the main
      cause of mutations in the CYP21 gene, random mutations can also be the cause of
      21-hydroxylase deficiency.

PMID- 18067084
TI  - [Fluorescence in situ hybridization identifies complex chromosomal aberrations in
      multiple myeloma].
AB  - OBJECTIVE: To explore the value of the technique of multiplex fluorescence in sit
      hybridization (M-FISH) combined with interphase fluorescence in situ
      hybridization (FISH) in the identification of the chromosomal aberrations in
      multiple myeloma (MM) and to investigate the frequency of 13q14 deletion, IgH
      translocations and 17p13 deletion. METHODS: Seven MM patients with complex
      chromosomal abnormalities (CCAs) were analyzed by combining the technique of
      conventional cytogenetics (CC) with M-FISH and FISH. RESULTS: M-FISH identified
      the aberrations which were undetected by CC, including twelve kinds of numeral
      aberrations and twenty-nine kinds of structural aberrations, In addition,
      abnormalities of chromosome 1, chromosomes 13 deletion and IgH translocations
      were the most frequent aberrations. Using the LSI D13S319 probe specific for
      13q14, we observed a deletion of 13q14 in 6 MM patients; using the LSI p53 probe
      specific for 17p13, we observed p53 deletion in 4 MM patients; using the LSI
      IGHC/IGHV probe specific for 14q32, we observed a translocation involving 14q32
      in 5 MM patients (43.5%), two translocations in two cases (case 6 and 7).
      CONCLUSION: M-FISH combined with FISH could refine the cytogenetics of MM
      patients and detect the missed abnormalities or correct the misidentified
      abnormalities analyzed by CC. It provides an ideal method for the research of
      chromosomal aberrations in MM.

PMID- 18067085
TI  - [Establishment of lymphocyte cell lines with abnormal chromosome karyotypes and
      its application in external quality assesment for chromosome karyotype analysis].
AB  - OBJECTIVE: To develop chromosome abnormal karyotype quality control cell and to
      explore the external quality assessment (EQA) method for chromosome karyotype
      analysis. METHODS: The chromosome abnormal karyotype quality control cells were
      prepared by EB virus (EBV) transfection of human B lymphocyte strain
      establishment and were distributed to participating labs for EQA test of
      chromosome karyotype analysis project at appointed time. The evaluation results
      were obtained through 4 grades scoring. RESULTS: Six kinds of chromosome abnormal
      karyotype quality control cells were initially developed, the karyotypes of which
      were 46,X, t(Y;5)(q12;q21), 46, XY, 15p +, 46, XX, t(13;18)(q12;q21), 46, X,
      r(Xp), 46,X,t(Y;Y), 46,XX,t(9;20)(p13;p13) respectively. In the external quality
      assessment, feedbacks from the participating labs on the sequencing results of
      the six kinds of quality control cells showed that the wholly overlapping rate
      were 82.1%, 92.0%, 84.6%, 80.8%, 86.2%, 74.1% and the wholly deviation rate were
      10.7%, 8.0%, 11.5%, 19.2%, 13.8%, 18.5%. The overall wholly overlapping rate,
      partial overlapping rate, partial deviation rate and wholly deviation rate turned
      out to be 83.2%, 0.6%, 2.5% and 13.7% respectively. CONCLUSION: The misdiagnose
      rate of chromosome karyotype analysis is rather high and regular external quality
      assessment is necessary to achieve dynamic information and improve diagnosis
      quality.

PMID- 18067086
TI  - [Application of tandem mass spectrometry on the diagnosis of fatty acid oxidation
      disorders].
AB  - OBJECTIVE: To screen and diagnose fatty acid oxidation disorders (FAOD) in high
      risk children with inborn error of metabolism using tandem mass spectrometry.
      METHODS: The study group consisting of 2941 high risk cases of suspected inborn
      error of metabolism was tested. The acylcarnitines in the dry blood filter papers
      of patients were tested by tandem mass spectrometry. The diagnosis of FAOD was
      according to the levels of the acylcarnitines, the clinical symptoms, and other
      biochemistry study. RESULTS: Fourteen patients were diagnosed as FAOD. These
      patients included one carnitine palmitoyltransferase deficiency I, one carnitine
      palmitoyltransferase deficiency II, one short-chain acyl-CoA dehydrogenase
      deficiency, seven medium-chain acyl-CoA dehydrogenase deficiency, two very long
      chain acyl-CoA dehydrogenase deficiency, and two multiple acyl-CoA dehydrogenase
      deficiency. CONCLUSION: FAOD are not rare in China. Analysis of acylcarnitines
      levels tested by tandem mass spectrometry is helpful to diagnose FAOD.

PMID- 18067087
TI  - [Clinical and laboratory investigation of hematological malignancy patients
      carrying 3q21q26 rearrangement].
AB  - OBJECTIVE: To investigate the clinical and laboratory characteristics of various
      hematopoietic malignant patients with t(3;3)(q21;q26) or inv(3) (q21q26).
      METHODS: Bone marrow samples were collected at presentation, prepared by short
      time unstimulated culture and R-binding, and karyotyped by conventional
      cytogenetical assay (CCA); megalokaryocytes were detected by Streptavidin-AKP
      (SAP); immunotype of the leukemia cells was tested by flow cytometric anylysis of
      surface antigens (FACS). RESULTS: All of the 9 hematopoietic malignant patients
      with t(3;3)(q21;q26) or inv(3) (q21q26) manifested myelodysplasia and poor
      treatment response. One of them relapsed shortly after allogenic hemotopoietic
      stem cell transplantation (allo-HSCT). CONCLUSION: Patients with 3q21q26
      rearrangement can be found in various hematopoietic malignances and demonstrate
      an unique entity. These patients show poor treatment response and have extremely
      poor prognosis.

PMID- 18067088
TI  - [Single-nucleotide polymorphisms of the cytidine deaminase gene in childhood with
      acute leukemia and normal Chinese children].
AB  - OBJECTIVE: Cytidine deaminase (CDA) is a key enzyme for metabolizing
      chemotherapeutic agent cytosine arabinoside (Ara-C), a deoxycytidine analog used
      for treatment of acute leukemia and lymphomas. Significant variability in the
      antitumor efficacy and systemic toxicity of Ara-C has been observed in cancer
      patients. Two missense mutations changing Ara-C sensitivity and toxicity had been
      found in the human CDA. Coding single-nucleotide polymorphisms (cSNPs) of CDA had
      been investigated in Japanese, Europeans Africans and Americans, but not in
      Chinese. The purpose of this study was to survey the allelic frequencies of CDA
      cSNPs in Chinese children. METHODS: The bone marrow samples from 87 childhood
      patients with acute leukemia and peripheral blood samples from 199 non-malignancy
      bearing children were obtained to prepare complementary DNAs (cDNAs). The cDNAs
      were analyzed for the polymorphisms in CDA by polymerase chain reaction (PCR)
      denaturing gradient gel electrophoresis (DGGE), PCR-restriction fragment length
      polymorphism (RFLP) and direct-sequencing. The distributive difference of each
      genotype was evaluated between children with acute leukemia and control children.
      RESULTS: Three known different polymorphisms, namely, 79A to C (K27Q), 208G to A
      (A70T) and 435T to C (silent) were identified in the coding region of CDA from
      the investigated Chinese population and displayed allelic frequencies of 12.1%,
      0.52% and 76.2%, respectively. No association with susceptibility to disease was
      observed. CONCLUSION: This study demonstrates 3 cSNPs and their allelic
      frequencies of CDA in Chinese children, and provides the first step to identify
      genetic markers for predicting variability in Ara-C response and toxicity.

PMID- 18067089
TI  - [Association of thiazide-sensitive Na+-Cl* cotransporter gene polymorphisms with
      the risk of essential hypertension].
AB  - OBJECTIVE: To investigate the association of thiazide-sensitive Na+ -Cl*
      cotransporter (TSC) gene 1784C/T and 2736G/A polymorphisms with the risk of
      essential hypertension (EH) in a Han nationality population. METHODS: A community
      based, case-control study including 190 EH patients and 94 sex- and age-matched
      controls was conducted. Genotypes of TSC gene 1784C/T and 2736G/A polymorphisms
      were analyzed by gene chip technology. RESULTS: The genotype (1784C/T CC, CT,
      TT:87, 88, 15 vs 36, 52, 6u2736G/A GG, AG, AA:167, 22, 1 vs 83, 10, 1) and
      alleles frequency (1784C/T C, T:68.9%, 31.1% vs 66.0%, 34.0%; 2736G/A G,A:93.7%,
      6.3% vs 93.6%, 6.4%) distribution of 1784C/T and 2736G/A showed no significant
      difference between the EH group and the control group (P >0.05). Moreover, no
      significant difference was observed in the frequencies distribution of four
      haplotypes (P > 0.05); Logistic regression analysis of haplotypes showed that the
      risk of EH had no significant difference in the population with different
      haplotypes (P > 0.05). CONCLUSION: The 1784C/T and 2736G/A polymorphisms of TSC
      gene may not play an important role in the etiology of EH in a Han nationality
      population. The studies in the future are warranted to validate our findings.

PMID- 18067090
TI  - [Analysis of chromosome mosaicism in preimplantation embryos by using 2
      sequential rounds of fluorescence in situ hybridization].
AB  - OBJECTIVE: To investigate the mechanism and factors affecting mosaicism in human
      preimplantation embryos by using 2 sequential rounds of fluorescence in situ
      hybridization(FISH). METHODS: Totally 51 normal fertilized embryos, which were
      not suitable for embryo transfer and cryopreservation, were analyzed on day 3
      after fertilization by using two sequential rounds of FISH. Chromosomes 13, 16,
      18, 21, 22, X and Y were analyzed. RESULTS: Among 51 embryos, 16 (31.4%) were
      mosaic, 12 (23.5%) were chaotic, and the remaining were either normal (27.5%) or
      non-mosaic abnormal (17.6%). The incidence of mosaic embryos was related to
      embryo developmental stage, for the incidence of mosaicism increased from 12.5%
      in embryos <or= 4 cell stage to 40.0% in 5-8 cell stage embryos. The aneuploidy
      rate for the patients over 35 years of age was significantly higher than that of
      the patients under 35 years (57.1% vs 23.3%). CONCLUSION: Mosaicism is common in
      human preimplantaion embryos, which may be one of the important factors affecting
      the success rates in IVF-ET. Most of the chromosomal abnormalities can be
      identified by two sequential rounds of FISH.

PMID- 18067091
TI  - [The building of chip-based capillary electrophoresis platform and application].
AB  - OBJECTIVE: To detect the point mutations by chip-based capillary electrophoresis
      and to provide a rapid and sensitive technique detection for beta-thalassemia.
      METHODS: Multiplex primer-extension reaction was used to amplify the common loci
      of the samples for beta-thalassemia. The reaction products were detected by the
      chip-based capillary electrophoresis and the genotypes of the samples were
      discrened. RESULTS: A system was constructed to detect the point mutations of
      beta-thalassemia by chip-based capillary electrophoresis, and the technology was
      ralidated by the patients' samples and the results coincided with those of
      detection kit. CONCLUSION: Beta-thalassemia can be detected by chip-based
      capillary electrophoresis rapidly with a small amount of samples. It would be a
      new detection method of the genetic disorders.

PMID- 18067092
TI  - [Genetic polymorphism of four X chromosome short temden repeats loci in Hebei Han
      population].
AB  - OBJECTIVE: To investigate the polymorphism of loci DXS6800, DXS6797, GATA172D05,
      DXS986 four loci in Hebei Han population. METHODS: The genome DNA of unrelated
      individuals,the families and rotten materials were extracted with phenol
      chloroform method and Chelex-100 method,respectively. The PCR products were
      detected by the polyacrylamide gel electrophoresis and DNA sequencing analysis.
      RESULTS: Among 150 unrelated males and 150 unrelated females from Hebei Han
      population, 25 alleles were found in the 4 loci. One hundred and thirty-eight
      haplotypes of the male were detected. The haplotype diversity reached 0.9986.
      CONCLUSION: The findings provided the polymorphic data of DXS6800, DXS6797,
      GATA172D05, and DXS986 loci in Hebei Han population. The four loci are relatively
      abundant in polymorphic information for identification and the obtained data of
      Hebei Han population can be applied to the X-STR genetic data bank.

PMID- 18067093
TI  - [Relationship between the polymorphism of the variable number of tandem repeats
      region 3' of the apolipoprotein B gene and serum lipid levels in the Guangxi
      Heiyi Zhuang populations].
AB  - OBJECTIVE: To study the relationship between the polymorphism of the variable
      number of tandem repeats region 3' of the apolipoprotein B gene (3'APOB-VNTR) and
      serum lipid levels in the Guangxi Heiyi Zhuang population. METHODS: A total of
      548 people of Heiyi Zhuang nationatity were surveyed by a cluster sampling.
      Epidemiological data were collected and serum lipid and apolipoprotein levels
      were measured. The genotypes and alleles of the 3' APOB-VNTR were determined by
      polymerase chain reaction combined with gel electrophoresis, and then analyzed by
      direct sequencing in the most common alleles. The results were compared with
      those in 496 people of Han nationality also live in that district. RESULTS: There
      were 19 alleles of the 3'APOB-VNTR in both ethnic groups. They were hypervariable
      elements (HVEs) 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54,
      56, 58, 60, 62 and 64, but HVEs 56 and 58 in Heiyi Zhuang nationality and HVEs 48
      and 62 in Han nationality were not be detected. The most common allele is HVE32
      in Heiyi and Zhuang nationality (25.9%), and HVE34 in Han nationality (27.2%).
      The frequencies of HVEs 26, 30, 46, heterozygote, and short alleles (< 38
      repeats, S) were higher in Heiyi Zhuang nationality than in Han nationality,
      whereas the frequencies of HVEs 34, 38, 40, homozygote, and long alleles (>or= 38
      repeats, L) were lower in Heiyi Zhuang nationality than in Han nationality. The
      levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C)
      and apolipoprotein (apo) B in Heiyi Zhuang nationality were higher in VNTR-LS
      (carrier of one long and one short alleles) than in VNTR-LL genotypes (the
      individual carrying two long alleles) genotypes. The levels of TC, triglycerides,
      HDL-C and apo B in Heiyi Zhuang nationality were also higher in homozygotes than
      in heterozygotes. There were no significant differences in the detected lipid
      parameters between the VNTR-SS (carrier of two short alleles) and VNTR-LS or VNTR
      LL genotypes in both ethnic groups. CONCLUSION: The 3'APOB-VNTR polymorphism is
      found to be significant difference between Heiyi Zhuang nationality and Han
      populations, and is associated with the serum lipid levels in Heiyi Zhuang
      nalionality but not in Han nationality.

PMID- 18067094
TI  - [Genetic polymorphisms of 9 X-chromosome short tandem repeat loci in a Inner
      Mongolia Ewenki population and their forensic evaluation].
AB  - OBJECTIVE: To investigate the alleles and genotypes frequency of 9 short tandem
      repeat (STR) loci on the X chromosome (DXS6789, DXS101, DXS8378, DXS7132,
      DXS7133, DXS7423, DXS6804, DXS6799, HPRTB) of Ewenki individuals living in Inner
      Mongolia Autonomous Region of China. METHODS: The 9 X-chromosomal STR loci were
      analyzed with polymerase chain reation (PCR), followed by polyacylamide gel
      electrophoresis and silver staining. Software SPSS13.0, Genepop, Fstat and
      Powerstats were used to evaluate their polymorphism diversity and potential
      forensic application. RESULTS: Allele frequencies and genotype frequencies of 99
      unrelated Ewenki individuals were obtained. Among the 9 loci, DXS6789, HPRTB
      showed less polymorphism and diversity in the population. The diversity of
      DXS7132 has no statistical difference between Ewenki population and other 4 Asian
      populations. CONCLUSION: Except DXS6789, HPRTB, the other 7 X-chromosomal STR
      loci are appropriate for individual identification, paternity test involving a
      female child, and studies on related disease. DXS7132 should be excluded when
      being used to distinguish diversity difference among populations.

PMID- 18067095
TI  - Celebrating Dr. Gotch's 80th birthday.

PMID- 18067096
TI  - Dialysis in the 1960s and the first hollow fiber dialyzer.
AB  - The history of the development of the first hollow fiber dialyzer as part of a
      federally funded project at Dow Chemical in Walnut Creek, California is
      interesting, as this project represented an initial step in the technical
      advances that dialysis has experienced over the last 40 years. The project,
      important in its own right, was revolutionary; the predominant design of
      dialyzers in use at the time employed either flat membranes or collapsed large
      cellulose tubing. The hollow fiber dialyzer project, in addition to being
      technologically important, brought together several individuals who over the
      intervening four decades have launched careers and collaborations that have had a
      profound impact, as well as resulting in major advances and contributions to a
      greater understanding of the dialysis process and adequate delivery of care.

PMID- 18067097
TI  - Membranes for dialysis: can we do without them?
AB  - Over the past five decades, membranes used for the treatment of chronic kidney
      disease have continuously evolved. In the course of this evolution, the use of
      classical non-modified cellulose membranes has declined in favor of cellulose
      based membranes in which the basic structure has been modified to improve the
      biocompatibility profile of the material as well as membranes based on synthetic
      polymers. In addition to providing improved biocompatibility, manufacturing
      methods have been innovatively adapted to produce membranes with optimized pore
      size and pore size distribution. This has led to the more effective removal of
      molecules involved in the development of complications associated with dialysis
      treatment. More recently, the approach has been move membranes beyond being just
      selective barriers with a high performance and to incorporate biological
      function. Despite these advances, membranes in current clinical use represent a
      compromise: while efficient in their removal of water soluble compounds, they are
      non selective, retain some bioreactivity and differ in their ability to adsorb
      endotoxins or bacterial fragments that may be present in the dialysis fluid. In
      this paper, an overview of the membranes used in current clinical practice and
      their limitations are discussed, together with approaches to solute transport in
      which no membranes are used.

PMID- 18067098
TI  - The association of the sodium "setpoint" to interdialytic weight gain and blood
      pressure in hemodialysis patients.
AB  - INTRODUCTION: Hemodialysis patients lack the normal mechanisms to regulate body
      water volume and osmolality. The dialysis treatment is expected to adequately
      regulate both body water volume and body Na+ content, which is the primary action
      determining body water osmolality. Data in subjects with normal renal function
      indicate that an individual has a specific osmolality value above which thirst is
      generated and fluid will be ingested. This specific osmolality value or
      "setpoint" varies among individuals, but is quite reproducible within an
      individual. It was postulated that hemodialysis patients also may have a Na+
      'setpoint', which if increased by the use of higher dialysate Na+ concentration,
      might be associated with increased interdialytic weight gain and blood pressure.
      METHODS: Monthly laboratory and treatment data were abstracted on 58 hemodialysis
      patients and included pre- and post-dialysis serum Na+ concentrations,
      interdialytic weight gain and blood pressure over 9 to 16 months. The Na+
      concentrations were averaged to determine the individual Na+ 'setpoint' and the
      Na+ gradient (Dialysis Na+ concentration - mean Na+ concentration) was determined
      for each patient. RESULTS: Linear regression analyses showed that there was a
      statistically significant association between the magnitude of the Na+ gradient
      and interdialytic weight gain and blood pressure. CONCLUSIONS: These data suggest
      that interdialytic weight gain in individual patients may be associated with the
      use of dialysate Na+ concentration in excess of the patient's desired Na+
      'setpoint'. More individualization of dialysate Na+ concentration may be
      indicated.

PMID- 18067099
TI  - Access flow measurement by indicator dilution without indicator injection: effect
      of switch location.
AB  - It is well known that the measurement of access flow by one of the various
      dilution techniques requires the reversal of blood flow drawn from and returned
      to the peripheral vascular access. But it was only recently recognized that the
      line switch itself constitutes a dilution experiment for certain blood and
      dialysate components and properties, so that a subsequent injection of indicator
      is no longer required. New switches introduced at different locations in the
      extracorporeal circulation not only simplify manual operation for standard access
      flow measurement but also provide an essential tool for the new technique, which
      is based on continuously measuring certain blood and/or dialysate characteristics
      and their changes caused by switching the bloodlines. In this study, the effects
      of switching the bloodlines at two different locations were studied when
      extracorporeal temperatures were used as a marker. The study shows that the
      temperature changes depend on the location of the switch relative to the
      extracorporeal temperature sensors, and that different algorithms to calculate
      access flow have to be used for the two possible switching positions to account
      for this dependence.

PMID- 18067100
TI  - Hyperlipidemia in chronic kidney disease.
AB  - The risk of cardiovascular events and mortality increases as renal function
      declines. The standard Framingham risk factors contributing to the relative risk
      of mortality (RRM) are altered or replaced. While obesity predicts loss of renal
      function, among dialysis patients obesity predicts survival rather than
      mortality. Among dialysis patients, Low Density Lipoprotein cholesterol (LDL)
      does not predict mortality; however other risk factors, such as low High Density
      Lipoprotein cholesterol (HDL) and increased intermediate density lipoproteins
      (IDL), remain cardiovascular risk factors. While HDL levels are decreased as a
      result of an increased fractional catabolic rate (FCR) both among obese patients
      with normal renal function and among dialysis patients, the mechanisms
      responsible for increased HDL FCR may differ. In patients with advanced kidney
      disease, HDL fails to mature normally as a result of decreased lecithin
      cholesterol ester transfer protein (LCAT), leaving cholesterol ester-poor,
      triglyceride (TG)-rich HDL3 and pre-beta-HDL. Chronic kidney disease (CKD) is
      associated with insulin resistance, providing another potential mechanistic link
      to low HDL levels. Increased TG levels are found in an expanded Intermediate
      Density Lipoprotein (IDL) pool and are associated with mortality risk.
      Lipoprotein (a) (LP(a)) levels are increased. In patients without renal disease,
      the concentration of Lp(a) is inversely associated with the size of the apo (a)
      isoform inherited; Lp (a) levels are increased in patients with kidney disease as
      consequence of increased concentrations, primarily of the high molecular weight
      isoform resulting from decreased clearance. Lp (a) levels are also associated
      with cardiovascular outcome among dialysis patients.

PMID- 18067101
TI  - The impact of visceral mass on survival in chronic hemodialysis patients.
AB  - In chronic hemodialysis, patient survival is positively correlated with body
      weight and body mass index (BMI). This relationship extends even to obese
      patients with a BMI >30 kg/m2. We have put forward the hypothesis that this
      survival benefit may be due to a lower average synthesis rate of uremic toxins
      (expressed as amount per time per unit of body weight) in larger patients,
      because the relative contribution of the high metabolic rate organs (HMRO) to
      body weight in these patients is lower and HMRO are most likely to be the prime
      source of uremic toxins. In addition, the average uremic toxin concentration in
      larger patients may be lower because of the larger distribution volume. Based on
      these assumptions, a better survival in patients with a lower HMRO to body weight
      fraction (HMRO%BW) can be predicted. To test this hypothesis we estimated gender-
      and race-specific HMRO mass by means of recently published regression models in
      2,004 incident hemodialysis patients. Cox proportional hazards models were used
      to assess the association between age, serum albumin concentration, eKt/V, and
      HMRO% BW and mortality. High HMRO%BW was significantly associated with increased
      mortality (hazard ratio 1.323 [95% CI: 1.186 to 1.477]). Mean survival time was
      longest in the low HMRO%BW tertile (1,031 days [95%CI: 974 to 1,087]), 935 days
      [95%CI: 886 to 984] in the middle, and 876 days [95%CI: 825 to 926] in the high
      HMRO%BW tertile (p<0.0001; log rank test). These results support the hypothesis
      predicting that a low HMRO mass per unit of weight confers a beneficial effect on
      survival.

PMID- 18067102
TI  - A mathematical model comparing solute kinetics in low- and high-BMI hemodialysis
      patients.
AB  - BACKGROUND: Patients with low Body Mass Index (BMI) on maintenance hemodialysis
      have a higher mortality risk than patients with elevated BMI. We investigated the
      use of kinetic modeling to test different hypotheses which have been advanced to
      explain this relationship. METHODS: Equations from a three-pool urea-kinetic
      mathematical model (hepatic mass, extracellular fluid, muscle mass and adipose
      tissue) were solved to yield predictive profiles of solute and putative toxin
      concentrations versus time for patients of different body weights. RESULTS: For
      the interdialytic interval, our mathematic model suggests that extracellular
      solute/toxin concentration increases more rapidly in small patients.
      Additionally, time average concentration (TAC) is higher for this cohort. A lower
      value of the muscle mass and adipose tissue mass-transfer coefficient (K(MMAT)),
      which determines the rate of solute release into the extracellular fluid,
      exacerbates this difference. CONCLUSION: These results suggest that higher
      mortality for smaller dialysis patients may be mediated by higher time average
      toxin concentration, especially for solutes with a low mass-transfer coefficient
      value.

PMID- 18067103
TI  - Patient empowerment in the management of hyperphosphatemia.
AB  - Despite advances in dialysis technology and an increasing variety of effective
      phosphate binders (PB) target phosphate levels are achieved in only a minority of
      ESRD patients. This is only partly explained by insufficient weekly phosphate
      elimination (2400 - 3000 mg) with traditional 3x 4-5 h dialysis, which is
      significantly lower than the total amount of phosphorus (iP) accrued from dietary
      consumption during the same period (about 5000 g). In addition, meal-to-meal and
      day-to-day variability of dietary iP intake in conjunction with inadequate
      phosphate binder dosing in relation to meal iP content also may contribute to
      hyperphosphatemia. It was hypothesized that self-adjusting of PB dose to meal iP
      content by the patient himself will improve management of hyperphosphatemia. A
      specific Phosphate-Education-Program (PEP) was developed to train patients to eye
      estimate meal iP content by "Phosphate Units" (PU), which categorize food
      components according to iP content (100 mg iP per serving size = 1 PU). To allow
      self-adjustment of PB dose to meal iP content, a new prescription concept for PB
      was required. Phosphate binders are no longer prescribed using a fixed dosing
      regimen but only in strict relation to meal iP content (#PB per PU). In close
      collaboration with the patient the PB/PU ratio is then adapted to individual
      patient needs until serum phosphate targets are met. This new management concept
      for hyperphosphatemia is the first to establish a direct link between dietary
      phosphorus intake and PB dose and to empower patients to self-adjust PB dose
      according to dietary phosphorus intake. Clinical studies are under way to
      establish the practical value of this new concept for CKD and ESRD patients.

PMID- 18067104
TI  - Newer strategies for anemia prevention in hemodialysis.
AB  - Anemia prevention for hemodialysis relies primarily on supplemental
      erythropoietin (EPO) and intravenous iron (IV-iron). The doses of EPO utilized
      are somewhat higher than normal endogenous rates of EPO production in healthy
      subjects, and the amount of IV-iron used to boost red blood cell (RBC) production
      may be greater than the amounts used for erythropoiesis. EPO and IV-iron might be
      used more efficiently if two fundamental problems were solved in the management
      of dialysis patients: better vitamin C status, and avoidance of chronic
      inflammation. The low levels of plasma vitamin C commonly observed in dialysis
      patients restrict mobilization of stored iron from the reticuloendothelial system
      (RES), and inflammation has a very similar effect. The impact of low vitamin C
      levels and concurrent inflammation causes a large amount of iron to be stored,
      with relatively inefficient utilization for erythropoiesis. Vitamin C intake for
      dialysis patients is often restricted because of avoidance of vitamin C-rich
      foods, and because of concerns about oxalosis. Inflammation is a chronic feature
      of renal disease, which is compounded by infections from use of catheters.
      Research strategies to improve vitamin C status and to decrease inflammation
      would lead to better utilization of iron and EPO, and could have parallel
      benefits for the long-term health of patients on hemodialysis.

PMID- 18067105
TI  - Cardiovascular risk in hemodialysis patients: a mechanistic approach.
AB  - A new formula is proposed to express the excess burden of cardiovascular risk
      faced by hemodialysis patients as a function of various inherent, acquired and
      potentially modifiable factors. The proposed equation CVR(HD) = CVR(B) X
      f(([CKD+HD]/[HD(tech)+Dr])+X) includes the terms: CVR(HD) (cardiovascular risk in
      hemodialysis patients); CVR(B) (baseline cardiovascular risk); CKD (risk
      associated with chronic kidney disease); HD (risks associated with the process of
      hemodialysis); HD(tech) (benefits of new hemodialysis technologies); Dr (benefits
      of drug therapies) and X (unknown or putative factors influencing cardiovascular
      morbidity). We review the various factors included in this proposed formula,
      touching upon the epidemiology, pathophysiology and therapeutic implications,
      including possible strategies to modify risk. As is apparent from the formula,
      CKD and HD in particular act as risk multipliers in augmenting or amplifying the
      baseline cardiovascular risk, while new hemodialysis technologies may provide an
      opportunity for "cardioprotective dialysis". Drug treatment may serve to mitigate
      some of the risk unique to this population.

PMID- 18067106
TI  - Glasses for seeing beyond visible.
AB  - Conventional glasses based on oxides have a transparency limited by phonon
      absorption in the near IR region and have a limited interest for analyzing
      information located far beyond the visible. The IR spectral domain is
      nevertheless of prime interest, since it covers fundamental wavelength ranges
      used for thermal imaging as well as molecular vibrational signatures. Besides
      spectacular advances in the field of IR detectors, the main significant
      progresses are related to the development of IR glass optics, such as lenses or
      IR optical fibres. The field of IR glasses is almost totally dominated by glasses
      formed from heavy atoms such as the chalcogens S, Se and Te. Their transparency
      extends up to 12, 16 and 28 microm for sulfide-, selenide- and the new generation
      of telluride-based glasses, respectively. They cover the atmospheric transparency
      domains, 3-5 and 8-13 microm, respectively, at which the IR radiation can
      propagate allowing thermal imaging and night-vision operations through thick
      layers of atmosphere. The development of new glass compositions will be discussed
      on the basis of structural consideration with the objective of moulding low-cost
      lenses for IR cameras used, for instance, in car-driving assistance.
      Additionally, multimode, single-index, optical fibres operating in the 3 to 12
      microm window developed for in situ remote evanescent-wave IR spectroscopy will
      also be mentioned. The detection of molecular IR signatures is applied to
      environmental monitoring for investigating the pollution of underground water
      with toxic molecules. The extension of this technique to the investigation of
      biomolecules in three different studies devoted to liver tissues analysis, bio
      film formation, and cell metabolism will also be discussed. Finally we will
      mention the developments in the field of single-mode fibres operating around 10
      mum for the Darwin space mission, which is aiming at discovering, signs of
      biological life in telluric earth-like exoplanets throughout the universe.

PMID- 18067107
TI  - Joziknipholones A and B: the first dimeric phenylanthraquinones, from the roots
      of Bulbine frutescens.
AB  - From the roots of the African plant Bulbine frutescens (Asphodelaceae), two
      unprecedented novel dimeric phenylanthraquinones, named joziknipholones A and B,
      possessing axial and centrochirality, were isolated, together with six known
      compounds. Structural elucidation of the new metabolites was achieved by
      spectroscopic and chiroptical methods, by reductive cleavage of the central bond
      between the monomeric phenylanthraquinone and -anthrone portions with sodium
      dithionite, and by quantum chemical CD calculations. Based on the recently
      revised absolute axial configuration of the parent phenylanthraquinones,
      knipholone and knipholone anthrone, the new dimers were attributed to possess the
      P-configuration (i.e., with the acetyl portions below the anthraquinone plane) at
      both axes in the case of joziknipholone A, whereas in joziknipholone B, the
      knipholone part was found to be M-configured. Joziknipholones A and B are active
      against the chloroquine resistant strain K1 of the malaria pathogen, Plasmodium
      falciparum, and show moderate activity against murine leukemic lymphoma L5178y
      cells.

PMID- 18067108
TI  - Specific binding effects for cucurbit[8]uril in 2,4,6-triphenylpyrylium
      cucurbit[8]uril host-guest complexes: observation of room-temperature
      phosphorescence and their application in electroluminescence.
AB  - 2,4,6-Triphenylpyrylium (TP(+)) forms host-guest complexes with cucurbiturils
      (CBs) in acidic aqueous solutions. (1)H NMR spectroscopic data indicates that
      complexation takes place by encapsulation of the phenyl ring at the four position
      within CB. Formation of the complex with CB[6] and CB[7] leads to minor shifts in
      the fluorescence wavelength maximum (lambda(fl)) or quantum yield (Phi(fl)). In
      sharp contrast, for complexes with CB[8], the emission results in the
      simultaneous observation of fluorescence (lambda(fl)=480 nm, Phi(fl)=0.05) and
      room-temperature phosphorescence (lambda(ph)=590 nm, Phi(ph)=0.15). The
      occurrence of room-temperature phosphorescence can be used to detect the presence
      of CB[8] visually in solution. Molecular modeling and MM2 molecular mechanics
      calculations suggest that this effect arises from locking the conformational
      mobility of the 2- and 6-phenyl rings as a result of CB[8] encapsulation. The
      remarkably high room-temperature phosphorescence quantum yield of the TP(+)@CB[8]
      complex has been advantageously applied to develop an electroluminescent cell
      that contains this host-guest complex. In contrast, analogous cells prepared with
      TP(+) or TP(+)@CB[7] fail to exhibit electroluminescence.

PMID- 18067109
TI  - Electrochemical insights into the mechanisms of proton reduction by
      [Fe2(CO)6{micro-SCH2N(R)CH2S}] complexes related to the [2Fe](H) subsite of
      [FeFe]hydrogenase.
AB  - Electrochemical investigations on a structural analogue of the [2Fe](H) subsite
      of [FeFe]H(2)ases, namely, [Fe(2)(CO)(6){micro-SCH(2)N(CH(2)CH(2)-
      OCH(3))CH(2)S}] (1), were conducted in MeCN/NBu(4)PF(6) in the presence of
      HBF(4)/Et(2)O or HOTs. Two different catalytic proton reduction processes
      operate, depending on the strength and the concentration of the acid used. The
      first process, which takes place around -1.2 V for both HBF(4)/Et(2)O and HOTs,
      is limited by the slow release of H(2) from the product of the {2 H(+)/2 e}
      pathway, 1-2H. The second catalytic process, which occurs at higher acid
      concentrations, takes place at different potentials depending on the acid
      present. We propose that this second mechanism is initiated by protonation of 1
      2H when HBF(4)/Et(2)O is used, whereas the reduction of 1-2H is the initial step
      in the presence of the weaker acid HOTs. The potential of the second process,
      which occurs around -1.4 V (reduction potential of 1-3H(+)) or around -1.6 V (the
      reduction potential of 1-2H) is thus dependent on the strength of the available
      proton source.

PMID- 18067110
TI  - Interface engineering of synthetic pores: towards hypersensitive biosensors.
AB  - Hydrophilic anchoring is introduced as a promising strategy to constructively
      control the various interactions of synthetic pore sensors with the surrounding
      biphasic environment. Artificial rigid-rod beta barrels are selected as classical
      synthetic multifunctional pores and random-coil tetralysines are attached as
      hydrophilic anchors. The synthesis of this advanced pore is accomplished in 32
      steps from commercially available starting materials. With regard to pore
      activity as such, the key impact of hydrophilic anchoring is a change from a Hill
      coefficient n<1 to n=4. This change confirms successful suppression of the
      competing self-assembly with precipitation from the aqueous phase as the origin
      of the accomplished increase in pore activity. The hydrophilic anchors do not
      interfere with the blockage of the synthetic pore sensors by anionic analytes. In
      the case of stoichiometric binding of blockers (K(D)=EC(50) of the pore;
      EC(50)=concentration needed to observe 50 % pore activity), however, the increase
      in pore activity achieved by hydrophilic anchoring results in improved pore
      blockage under high dilution conditions. Controls confirm that this increase does
      not occur with analytes that do not exhibit stoichiometric binding (K(D)>EC(50)).
      These results not only reveal stoichiometric binding as the expected origin of
      the sensitivity limit of synthetic pore sensors, they also provide promising
      solutions for this problem. The combination of hydrophilic anchoring with
      targeted pore formation emerges as a particularly promising strategy to further
      reduce effective pore concentrations. The scope and limitations of this approach
      are exemplified with pertinent analyte pairs that are essential for the sensing
      of sucrose, lactose, acetate, and glutamate with synthetic pores in samples from
      the supermarket.

PMID- 18067111
TI  - Aqueous-phase Fischer-Tropsch synthesis with a ruthenium nanocluster catalyst.

PMID- 18067112
TI  - Structurally defined reactions of sodium TMP-zincate with nitrile compounds:
      synthesis of a salt-like sodium sodiumdizincate and other unexpected ion-pair
      products.

PMID- 18067113
TI  - Activation of sp3 carbon-hydrogen bonds by a ruthenium(II) complex and subsequent
      metal-mediated C-C and C-N bond formation.

PMID- 18067114
TI  - Trialkylammoniododecaborates: anions for ionic liquids with potassium, lithium
      and protons as cations.
AB  - Herein we report a new class of low-melting ionic liquids (IL) that consist of
      N,N,N-trialkylammonioundecahydrododecaborates(1-) as the anion and a range of
      cations. The cations include the common cations of conventional ILs such as
      tetraalkylammonium, N-alkylpyridinium, and N-methyl-N'-alkylimidazolium. In
      addition, their salts with lithium, potassium, and proton cations also exist as
      ILs. Pulse radiolysis studies indicate that the anions do not react with solvated
      electrons.

PMID- 18067115
TI  - Highly enantioselective reactions of configurationally labile epimeric diamine
      complexes of lithiated S-benzyl thiocarbamates.
AB  - Substitution reactions that employ primary-carbamoyl-protected arylmethanethiols
      are described. The enantiodetermining step was found to occur in the post
      deprotonation step as a dynamic thermodynamic resolution with a chiral
      bis(oxazoline) ligand. The configurationally labile lithium complexes were
      trapped with various electrophiles to yield different substitution products in
      good to excellent yields and enantiomeric excesses. The absolute configurations
      of the substitution products were determined, and the stereochemical pathway of
      the substitution reaction was elucidated for different classes of electrophiles.
      The temperature-dependent epimerization process was monitored by 1H and 6Li NMR
      spectroscopy.

PMID- 18067116
TI  - HMGA1a protein unfolds or refolds synthetic DNA-chromophore hybrid polymers: a
      chaperone-like behavior.
AB  - High group mobility protein, HMGA1a, was found to play a chaperone-like role in
      the folding or unfolding of hybrid polymers that contained well-defined synthetic
      chromophores and DNA sequences. The synthetic and biological hybrid polymers
      folded into hydrophobic chromophoric nanostructures in water, but existed as
      partially unfolded configurations in pH or salt buffers. The presence of HMGA1a
      induced unfolding of the hybrid DNA-chromophore polymer in pure water, whereas
      the protein promoted refolding of the same polymer in various pH or salt buffers.
      The origin of the chaperone-like properties probably comes from the ability of
      HMGA1a to reversibly bind both synthetic chromophores and single stranded DNA.
      The unfolding mechanisms and the binding stoichiometry of protein-hybrid polymers
      depended on the sequence of the synthetic polymers.

PMID- 18067118
TI  - CD133: molecule of the moment.
AB  - CD133 (prominin-1) was the first in a class of novel pentaspan membrane proteins
      to be identified in both humans and mice, and was originally classified as a
      marker of primitive haematopoietic and neural stem cells. Due to the highly
      restricted expression of CD133 family molecules on plasma membrane protrusions of
      epithelial and other cell types, in association with membrane cholesterol, a role
      in the organization of plasma membrane topology has also recently been assigned
      to this family. Studies have now confirmed the utility of CD133 as a marker of
      haematopoietic stem cells for human allogeneic transplantation. In addition,
      CD133 represents a marker of tumour-initiating cells in a number of human
      cancers, and therefore it may be possible to develop future therapies towards
      targeting cancer stem cells via this marker. The development of such therapies
      will be aided by a clearer understanding of the molecular mechanisms and
      signalling pathways that regulate the behaviour of CD133-expressing cells, and
      new data outlining the role of Wnt, Notch, and bone morphogenetic protein (BMP)
      signalling in CD133(+) cancer stem cell regulation are discussed within.

PMID- 18067119
TI  - An ectocranial lesion on the Middle Pleistocene human cranium from Hulu Cave,
      Nanjing, China.
AB  - The earlier Middle Pleistocene human partial cranium from Hulu Cave, Tangshan,
      Nanjing (Hulu 1) exhibits an ectocranial lesion which covers most of the anterior
      neurocranium, largely between the temporal lines and extending from the
      supratoral sulcus to the anterior parietal bone. The endocranial surfaces and the
      remainder of the cranium (upper facial skeleton, lateral frontal bone, posterior
      parietal bones, and mid-occipital bone) are normal. The healed lesion exhibits
      both resorption and the laying down of new bone. Differential diagnosis suggests
      that the lesion was caused by either trauma (broad compressive trauma, tensile
      trauma to the scalp, or partial scalp removal) or burning (with damage to scalp
      and superficial neurocranium). Dietary deficiencies, infection, and neoplastic
      disorders do not fit the lesion characteristics. The Hulu 1 specimen therefore
      joins a growing sample of Pleistocene Homo remains with nonfatal and nontrivial
      disorders.

PMID- 18067120
TI  - Skeletal pathology in Pan troglodytes schweinfurthii in Kibale National Park,
      Uganda.
AB  - The ecological pressures shaping chimpanzee anatomy and behavior are the subject
      of much discussion in primatology and paleoanthropology, yet empirical data on
      fundamental parameters including body size, morbidity, and mortality are rare for
      wild chimpanzees. Here, we present skeletal pathology and body size data for 20
      (19 crania, 12 postcrania) chimpanzees (Pan troglodytes schweinfurthii) from
      Kibale National Park, Uganda. We compare these data with other East African
      populations, especially Gombe National Park. Estimated body size for Kibale
      chimpanzees was similar to other East African populations and significantly
      larger than Gombe chimpanzees. The high rates of trauma and other skeletal
      pathology evident in the Kibale chimpanzee skeletons were similar to those in the
      Gombe skeletal sample. Much of the major skeletal trauma in the Kibale skeletons
      was attributable to falls, although other pathologies were noted as well,
      including apparent injuries from snares, degenerative arthritis, and minor
      congenital abnormalities.

PMID- 18067121
TI  - Crohn's disease and color Doppler sonography: response to treatment and its
      relationship with long-term prognosis.
AB  - PURPOSE: To evaluate the ability of sonography to detect changes in patients
      undergoing treatment for Crohn's disease and whether these findings are related
      to the patient's long-term outcome. METHODS: Twenty-eight patients with Crohn's
      disease were examined prospectively using gray-scale and color Doppler sonography
      before and during treatment. Three sonographic examinations were made: on the
      first day of treatment, between 3 and 8 days later, and approximately 4 weeks
      after starting the treatment. Sonographic examination included an evaluation of
      maximum bowel wall thickness and vascularity pattern. The sonographic data were
      compared with clinical and laboratory data, and possible relation with the
      patient's long-term outcome was considered. RESULTS: Initial baseline sonograms
      revealed at least 1 thickened segment of the bowel wall in all of the patients.
      In this initial examination, 18 of 22 patients (81%) with clinically active
      disease had moderate or marked parietal vascularity. A statistically significant
      reduction in the vascularity of the affected bowel was observed on the third
      sonographic examination (p < 0.05). Seventeen patients who were in clinical
      remission had relapses and were treated with immunosuppressive therapy or surgery
      during the follow-up. Eighty-six percent of the patients with residual hyperemia
      on sonographic examination after treatment had an unfavorable clinical course
      compared with only 30% of the patients with no, or barely visible, residual
      hyperemia (p < 0.01). CONCLUSION: Sonography can identify bowel inflammation and
      its changes during treatment. In patients with Crohn's disease, hyperemia on
      color Doppler sonography during clinical remission after treatment may reflect an
      increased risk of relapse.

PMID- 18067122
TI  - What does geometric mean, mean geometrically? Assessing the utility of geometric
      mean and other size variables in studies of skull allometry.
AB  - This study investigated the effects of using different size variables for
      interpretations of relative orbit size and mandibular robusticity. Thirty-three
      skull measurements taken on 385 platyrrhines representing 12 of 16 New World
      monkey genera (in addition to body mass and total body length) were used singly
      and in combinations (by taking the geometric mean of all measurements) as size
      variables to produce relative size indices of orbit area and mandibular
      thickness. These indices were then compared to investigate which size variables
      proved effective at differentiating nocturnal from diurnal taxa and hard object
      from soft object feeders based upon results from previous biomechanical studies.
      It was found that certain groups of size variables consistently produced the a
      priori expectations and resulted in lower coefficients of variation. The general
      principles shared by these size variables were that they sampled anatomically
      remote regions of the skull that appear to be functionally independent from the
      trait being evaluated and they were nearly always geometric mean combinations
      composed of a relatively high number (>or=12) of large measurements. Suggestions
      are also presented for amending these principles for use with incomplete material
      such as fossils.

PMID- 18067123
TI  - Improved detection of branching points in algorithms for automated neuron tracing
      from 3D confocal images.
AB  - Automated tracing of neuronal processes from 3D confocal microscopy images is
      essential for quantitative neuroanatomy and neuronal assays. Two basic approaches
      are described in the literature-one based on skeletonization and another based on
      sequential tracing along neuronal processes. This article presents algorithms for
      improving the rate of detection, and the accuracy of estimating the location and
      process angles at branching points for the latter class of algorithms. The
      problem of simultaneously detecting branch points and estimating their
      measurements is formulated as a generalized likelihood ratio test defined on a
      spatial neighborhood of each candidate point, in which likelihoods were computed
      using a ridge detection approach. The average detection rate increased from from
      37 to 86%. The average error in locating the branch points decreased from 2.6 to
      2.1 voxels in 3D images. The generalized hypothesis test improves the rate of
      detection of branching points, and the accuracy of location estimates, enabling a
      more complete extraction of neuroanatomy and more accurate counting of branch
      points in neuronal assays. More accurate branch point morphometry is valuable for
      image registration and change analysis.

PMID- 18067124
TI  - A flow cytometric protocol for detection of Cryptosporidium spp.
AB  - Cryptosporidium parvum is transmitted through water and can cause severe
      diarrhea. The diagnosis is usually based upon observer-dependent microscopic
      detection of oocysts, with rather low sensitivity and specificity. Our objective
      was to optimize a flow cytometric (FC) protocol for the detection of C. parvum. A
      specific monoclonal antibody conjugated with R-phycoerythrin was incubated with
      dead oocysts to determine the optimal antibody concentration. Serial
      concentrations of oocysts were stained with the optimized concentration and
      analyzed by FC. The lower detection limit was determined, and the possibility of
      cross-reaction was investigated using prokaryotic and eukaryotic microorganisms.
      A FC protocol was optimized to detect oocysts in spiked human stools. The optimal
      antibody concentration was found to be 3.0 mug/ml. The lowest number detectable
      was 2 x 10(3) oocysts/ml. Staining procedure was specific, as no cross-reactions
      were observed. This reliable and easy FC protocol allow the specific detection of
      Cryptosporidium oocysts, even at very low concentrations, which is important for
      public health and further studies of treatment efficacy.

PMID- 18067125
TI  - Three-dimensional sonographic measurement of contralateral lung volume in fetuses
      with isolated congenital diaphragmatic hernia.
AB  - PURPOSE: To use 3-dimensional sonography (3DUS) to measure contralateral lung
      volume and evaluate the potential of this measurement to predict neonatal outcome
      in isolated congenital diaphragmatic hernia (CDH). METHODS: Between January 2002
      and December 2004, the contralateral lung volumes of 39 fetuses with isolated CDH
      were measured via 3DUS using rotational multiplanar imaging. The
      observed/expected contralateral fetal lung volume ratios (o/e-ContFLVR) were
      compared with the lung/head ratio (LHR), observed/expected total fetal lung
      volume ratio (o/e-TotFLVR), and postnatal outcome. RESULTS: Contralateral lung
      volumes are less reduced than total lung volumes in CDH. The bias and precision
      of 3DUS in estimating contralateral lung volumes were 0.99 cm(3) and 1.11 cm(3),
      respectively, with absolute limits of agreement ranging from -1.19 cm(3) to +3.17
      cm(3). The o/e-ContFLVR was significantly lower in neonatal death cases (median,
      0.49 cm(3); range, 0.22-0.99 cm(3)) than in survival cases (median, 0.58 cm(3);
      range, 0.42-0.92 cm(3) [p < 0.01]). Overall accuracy of the o/e-ContFLVR, o/e
      TotFLVR, and LHR in predicting neonatal death were 67.7% (21/31), 80.7% (25/31),
      and 77.4% (24/31), respectively. CONCLUSION: Although o/e-ContFLVR can be
      precisely measured with 3DUS and can be used to predict neonatal death in CDH, it
      is less accurate than LHR and o/e-TotFLVR for that purpose.

PMID- 18067126
TI  - Sonography of endometriosis in infrequent sites.
AB  - We reviewed the sonographic features of endometriosis in infrequent sites,
      including the abdominal wall, appendix, perineum, and bladder. Familiarity with
      the clinical setting and the sonographic appearance of endometriosis in both
      frequent and infrequent sites can help facilitate prompt, accurate diagnosis and
      treatment.

PMID- 18067127
TI  - Early antenatal diagnosis of spina bifida presenting with a "step" in the
      posterior contour of an 8-week embryo.
AB  - We report a case of spina bifida in the upper thoracic spine with an accompanying
      meningocoele suspected at 8 weeks' gestation via transvaginal sonography and
      confirmed at 13 weeks' gestation via 3-dimensional sonography. The fetal cranial
      vault and intracranial structures were normal. The only finding in the 8-week
      sonogram was a subtle angulation or "step" in the posterior contour of the
      embryo; this may be attributed to kyphosis, which often accompanies this
      condition. The presence of a "step" in the fetal contour must alert the
      sonologist to the possibility of spina bifida. To our knowledge, this is the
      earliest antenatal diagnosis of spina bifida.

PMID- 18067128
TI  - Regulatory roles of tumor-suppressor proteins and noncoding RNA in cancer and
      normal cell functions.
AB  - We describe a mechanism for reversible regulation of gene transcription, mediated
      by a family of tumor-suppressor proteins (TSP) containing a DNA-binding domain
      (DBD) that binds to a gene and represses transcription, and RNA-binding domains
      (RBDs) that bind RNA, usually a noncoding RNA (ncRNA), forming a TSP/RNA complex
      that releases the TSP from a gene and reverses repression. This mechanism appears
      to be involved in the regulation of embryogenesis, oncogenesis, and
      steroidogenesis. Embryonic cells express high levels of RNA that bind to a TSP
      and prevent repression of proto-oncogenes that drive cell proliferation. The
      level of the RNA subsequently decreases in most differentiating cells, enabling a
      TSP to repress proto-oncogenes and stop cell proliferation. Oncogenesis can
      result when the level of the RNA fails to decrease in a proliferating cell or
      increases in a differentiated cell. This mechanism also regulates transcription
      of P450scc, the first gene in the steroidogenic pathway.

PMID- 18067129
TI  - Mass screening programmes and trends in cervical cancer in Finland and the
      Netherlands.
AB  - With respect to cervical cancer management, Finland and the Netherlands are
      comparable in relevant characteristics, e.g., fertility rate, age-of-mother at
      first birth and a national screening programme for several years. The aim of this
      study is to compare trends in incidence of and mortality from cervical cancer in
      Finland and the Netherlands in relation to the introduction and intensity of the
      screening programmes. Therefore, incidence and mortality rates were calculated
      using the Cancer Registries of Finland and the Netherlands. Data on screening
      intensity were obtained from the Finnish Cancer Registry and the Dutch evaluation
      centre at ErasmusMC-Rotterdam. Women aged 30-60 have been screened every 5 years,
      in Finland since 1992 and in the Netherlands since 1996. Screening protocols for
      smear taking and referral to the gynaecologist are comparable. Incidence and
      mortality rates have declined more in Finland. In 2003, age-adjusted incidence
      and mortality in Finland were 4.0 and 0.9 and in the Netherlands 4.9 and 1.4 per
      100,000 woman-years, respectively. Excess smear use in the Netherlands was
      estimated to be 24 per 1,000 women during a 5-year interval compared to 121 in
      Finland. The decline in mortality in Finland seems to be almost completely
      related to the screening programme whereas in the Netherlands it was initially
      considered to be a natural decline. Differences in risk factors might also play a
      role: the Netherlands has higher population density and higher percentages of
      immigrants and (female) smokers. The greater excess smear use in Finland might
      also have affected incidence.

PMID- 18067130
TI  - MC1R variants associated susceptibility to basal cell carcinoma of skin:
      interaction with host factors and XRCC3 polymorphism.
AB  - The variants within the human melanocortin 1 receptor (MC1R) gene are associated
      with an increased risk of different skin cancers. In this study, we genotyped by
      direct sequencing, 529 cases of basal cell carcinoma of the skin (BCC) and 533
      healthy controls for polymorphisms in the entire MC1R gene. In addition to 10
      common polymorphisms, we detected 23 rare variants in the gene. The presence of
      any nonsynonymous MC1R variant was associated with an increased risk in the
      carriers (odds ratio OR 1.66, 95% confidence interval CI 1.28-2.14) corresponding
      to a population attributable fraction of about 27%. The odds ratio for the risk
      in the carriers of 2 MC1R variants was 2.69 (95% CI 1.77-4.08). The risk of BCC
      in the carriers of MC1R variants with fair complexion was almost twice as much as
      in the corresponding noncarriers. The carriers of the R163Q variant with a medium
      skin complexion were at a 3-fold higher risk than the noncarrier counterparts.
      The interaction, of effect on the BCC risk, between the MC1R variants and types
      of skin response to sun exposure was greater than multiplicative. We also
      observed a multiplicative interaction of risk due to the MC1R variants and the
      common allele (high risk) of the T241M polymorphism in the XRCC3 gene. Our data
      confirmed the status of the nonsynonymous MC1R variants as independent genetic
      risk factors for BCC. However, the mechanism through which the variants influence
      the risk likely involves complex interactions with other genetic and host risk
      factors.

PMID- 18067131
TI  - Leukaemia in young children living in the vicinity of German nuclear power
      plants.
AB  - A case control study was conducted where cases were children younger than 5 years
      (diseased between 1980 and 2003) registered at the german childhood cancer
      registry (GCCR). Population-based matched controls (1:3) were selected from the
      corresponding registrar's office. Residential proximity to the nearest nuclear
      power plant was determined for each subject individually (with a precision of
      about 25 m). The report is focused on leukaemia and mainly on cases in the inner
      5-km zone around the plants. The study includes 593 leukaemia cases and 1,766
      matched controls. All leukaemia combined show a statistically significant trend
      for 1/distance with a positive regression coefficient of 1.75 [lower 95%
      confidence limit (CL): 0.65]; for acute lymphoid leukaemia 1.63 (lower 95%-CL:
      0.39), for acute nonlymphocytic leukaemia 1.99 (lower 95%-CL: -0.41). This
      indicates a negative trend for distance. Cases live closer to nuclear power
      plants than the randomly selected controls. A categorical analysis shows a
      statistically significant odds ratio of 2.19 (lower 95%-CL: 1.51) for residential
      proximity within 5 km compared to residence outside this area. This result is
      largely attributed to cases in previous studies of the GCCR (especially in the
      inner zone) as there is clearly some overlap between those studies. The result
      was not to be expected under current radiation-epidemiological knowledge.
      Considering that there is no evidence of relevant accidents and that possible
      confounders could not be identified, the observed positive distance trend remains
      unexplained.

PMID- 18067132
TI  - Natural agents targeting the alpha7-nicotinic-receptor in NSCLC: a promising
      prospective in anti-cancer drug development.
AB  - Nicotinic acetylcholine receptors (nAChR) are expressed on normal bronchial
      epithelial and nonsmall cell lung cancer (NSCLC) cells and are involved in cell
      growth regulation. Nicotine induced cell proliferation. The purpose of this study
      was to determine if interruption of autocrine nicotinic cholinergic signaling
      might inhibit A549 NSCLC cell growth. For this purpose alpha-Cobratoxin (alpha
      CbT), a high affinity alpha7-nAChR antagonist was studied. Cell growth decrease
      was evaluated by Clonogenic and MTT assays. Evidence of apoptosis was identified
      staining cell with Annexin-V/PI. Characterization of the basal NF-kappaB activity
      was done using the Trans-AM NF-kappaB assay colorimetric kit. "In vivo"
      antitumour activity was evaluated in orthotopically transplanted nude mice
      monitored by In vivo Imaging System technology. alpha-CbT caused concentration
      dependent cell growth decrease, mitochondrial apoptosis caspases-9 and 3
      dependent, but caspase-2 and p53-independent and down-regulation of basal high
      levels of activated NF-kappaB. alpha-CbT treatment determines a significant
      reduction of tumor growth in nude mice orthotopically engrafted with A549
      luciferase cells (4.6% of living cells vs. 31% in untreated mice). No sign of
      toxicity was reported related to treatment. These findings suggest that alpha7
      nAChR antagonists namely alpha-CbT may be useful adjuvant for treatment of NSCLC
      and potentially other cancers.

PMID- 18067133
TI  - Alcohol intake and risk of breast cancer defined by estrogen and progesterone
      receptor status--a meta-analysis of epidemiological studies.
AB  - The association between alcohol consumption and an increased risk of breast
      cancer has been established. It is still unclear however, whether this
      relationship differs across the estrogen receptor (ER) and progesterone receptor
      (PR) tumors subtypes. To provide a quantitative assessment of the association
      between alcohol intake and the risk of ER-/PR-defined breast cancer, we conducted
      a meta-analysis of cohort and case-control studies. Studies were identified by a
      literature search of PubMed through April 20, 2007 and by searching the reference
      lists of relevant articles. Summarized risk estimates (REs) with 95% confidence
      intervals (CIs) were calculated using random-effects models. The summarized
      results of the meta-analysis comparing the highest versus the lowest consumption
      categories showed statistically significant higher risks of developing all ER+
      (27%), all ER- (14%), ER+PR+ (22%) and ER+PR- (28%), but not ER-PR- tumors. The
      dose-response meta-analysis showed that an increase in alcohol consumption of 10
      g of ethanol per day was associated with statistically significant increased
      risks for all ER+ (12%), all ER- (7%), ER+PR+ (11%) and ER+PR- (15%), but not ER
      PR-. A statistically significant heterogeneity of the REs across all ER+ versus
      ER-PR- was observed (p(heterogeneity) = 0.02). The summarized results from
      studies with adjustment for postmenopausal hormone use, body mass index and
      family history of breast cancer were higher and statistically significantly
      different from those without. The observed positive associations with alcohol for
      ER+PR+ and ER+PR- tumors cannot be explained by estrogen-dependent pathway only.
      Further studies need to clarify the biological mechanisms.

PMID- 18067134
TI  - Differential diagnosis of myotonic disorders.
AB  - The presence of myotonia and paramyotonia on clinical examination and of myotonic
      discharges during electrodiagnostic (EDX) studies are important for the diagnosis
      of certain neuromuscular conditions. The increased muscle activity of myotonia
      produces muscle stiffness that improves with repeated activity. Paramyotonia
      produces a similar symptom, but the stiffness paradoxically increases with
      activity. Myotonic discharges are easily recognized on EDX testing because of the
      waxing and waning discharges. Myotonic dystrophy and myotonia congenita share
      both clinical and electrodiagnostic myotonia. Paramyotonia congenita and
      hyperkalemic periodic paralysis are associated with clinical paramyotonia and
      electrical myotonia. Acid maltase deficiency often produces myotonic potentials
      without clinical evidence of myotonia or paramyotonia. The differential diagnosis
      of these myotonic disorders is discussed.

PMID- 18067135
TI  - Cognitive deficits in Tsc1+/- mice in the absence of cerebral lesions and
      seizures.
AB  - OBJECTIVE: Tuberous sclerosis complex (TSC) is characterized by brain lesions,
      epilepsy, increased incidence of mental retardation and autism. The causal link
      between lesion load and epilepsy on cognitive disabilities has been debated, and
      these factors explain only part of the intelligence quotient variability. A Tsc2
      rat model of the disease provided evidence that the TSC genes are directly
      involved in neuronal function. However, these lesion- and epilepsy-free animals
      did not show learning deficits, leaving open the possibility that the presence of
      brain lesions or epilepsy is a prerequisite for the cognitive deficits to fully
      develop. Here, we reinvestigated the relation among cerebral lesions, epilepsy,
      and cognitive function using Tsc1+/- mice. METHODS: We used immunocytochemistry
      and high-resolution magnetic resonance imaging to study the presence of neuronal
      pathology in Tsc1+/- mice. We used the Morris water maze, fear conditioning,
      social interaction, and nest building test to study the presence of cognitive and
      social deficits. RESULTS: We observed no spontaneous seizures or cerebral lesions
      in the brains of Tsc1+/- mice. In addition, giant dysmorphic cells were absent,
      and spine number and dendritic branching appeared to be normal. Nevertheless,
      Tsc1+/- mice showed impaired learning in the hippocampus-sensitive versions of
      the learning tasks and impaired social behavior. INTERPRETATION: Tsc1+/- mice
      show social and cognitive deficits in the absence of apparent cerebral pathology
      and spontaneous seizures. These findings support a model in which
      haploinsufficiency for the TSC genes leads to aberrations in neuronal functioning
      resulting in impaired learning and social behavior.

PMID- 18067136
TI  - Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia.
AB  - OBJECTIVE: Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group
      of neurodegenerative disorders resulting in progressive spasticity of the lower
      limbs. One form of autosomal recessive hereditary spastic paraplegia (ARHSP) with
      thin corpus callosum (TCC) was linked to chromosomal region 15q13-21 (SPG11) and
      associated with mutations in the spatacsin gene. We assessed the long-term course
      and the mutational spectrum of spatacsin-associated ARHSP with TCC. METHODS:
      Neurological examination, cerebral magnetic resonance imaging (MRI),
      18fluorodeoxyglucose positron emission tomography (PET), nerve biopsy, linkage
      and mutation analysis are presented. RESULTS: Spastic paraplegia in patients with
      spatacsin mutations (n = 20) developed during the second decade of life. The
      Spastic Paraplegia Rating Scale (SPRS) showed severely compromised walking
      between the second and third decades of life (mean SPRS score, >30). Impaired
      cognitive function was associated with severe atrophy of the frontoparietal
      cortex, TCC, and bilateral periventricular white matter lesions. Progressive
      cortical and thalamic hypometabolism in the 18fluorodeoxyglucose PET was
      observed. Sural nerve biopsy showed a loss of unmyelinated nerve fibers and
      accumulation of intraaxonal pleomorphic membranous material. Mutational analysis
      of spatacsin demonstrated six novel and one previously reported frameshift
      mutation and two novel nonsense mutations. Furthermore, we report the first two
      splice mutations to be associated with SPG11. INTERPRETATION: We demonstrate that
      not only frameshift and nonsense mutations but also splice mutations result in
      SPG11. Mutations are distributed throughout the spatacsin gene and emerge as
      major cause for ARHSP with TCC associated with severe motor and cognitive
      impairment. The clinical phenotype and the ultrastructural analysis suggest a
      disturbed axonal transport of long projecting neurons.

PMID- 18067137
TI  - Comparison of perception threshold testing and thermal-vibratory testing.
AB  - Current perception threshold testing (CPT) is thought to selectively activate and
      measure three types of afferent nerves. However, it has not been standardized or
      compared with better-studied methods of sensory testing. Our objectives were to
      determine the relationship between CPT (2000 Hz, 250 Hz, 5 Hz) and quantitative
      sensory testing (QST) using vibratory and heat thresholds, and to assess the test
      retest reliability of both methods. Twenty-seven healthy women were enrolled.
      Each woman underwent CPT and QST on the volar part of the arm. Sensory thresholds
      were determined by the method of limits; 20 women underwent repeated CPT testing
      and QST after 1 week to determine test-retest reliability. Thermal thresholds
      were moderately correlated with CPT at 5 Hz (rho = 0.49, P = 0.009), as were
      vibratory thresholds and CPT at 2000 Hz (rho = 0.5, P = 0.008). In contrast to
      CPT measurements, warm and vibratory and cold thresholds were correlated 1 week
      apart (rho = 0.73, P = 0.0001; rho = 0.83, P = 0.0001; and rho = 0.47, P =
      0.0037, respectively). CPT testing and QST seem to be measuring similar afferent
      nerve-fiber populations, but QST has better test-retest reliability than CPT
      testing, justifying its role in clinical or research studies.

PMID- 18067138
TI  - Quantitative motor unit potential analysis in the diaphragm: a normative study.
AB  - Although quantitative motor unit potential (MUP) analysis has an established role
      in other skeletal muscles, it has not been performed in the diaphragm. The aim of
      the present study was to test whether such studies are possible and to establish
      normative data. Twenty-nine healthy volunteers (15 men), aged 21-65 years
      (median, 33 years), were studied using standard concentric needle electrodes, and
      equipment with the facility for template-operated multi-MUP analysis. Needle
      electrodes were inserted into the right medial recess of the seventh to ninth
      intercostal spaces. During MUP sampling, subjects were asked to hold their breath
      in partial inspiration for 5 s. At least 20 MUPs were obtained in 28 subjects.
      Diaphragmatic MUPs were confirmed to be much smaller than those of limb muscles.
      We found diaphragmatic quantitative MUP analysis to be possible in healthy
      volunteers. However, further studies in patient groups are needed to establish
      the feasibility and clinical value of such studies.

PMID- 18067139
TI  - Localization of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)
      expression in mouse brain: A new perspective on N-acylethanolamines as neural
      signaling molecules.
AB  - N-acylethanolamines (NAEs) are membrane-derived lipids that are utilized as
      signaling molecules in the nervous system (e.g., the endocannabinoid anandamide).
      An N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) that catalyzes
      formation of NAEs was recently identified as a member of the zinc
      metallohydrolase family of enzymes. NAPE-PLD(-/-) mice have greatly reduced brain
      levels of long-chain saturated NAEs but wild-type levels of polyunsaturated NAEs
      (e.g., anandamide), suggesting an important role for NAPE-PLD in the biosynthesis
      of at least a subset of endogenous NAEs in the mammalian nervous system. To
      provide a neuroanatomical basis for investigation of NAPE-PLD function, here we
      have analyzed expression of NAPE-PLD in the mouse brain using mRNA in situ
      hybridization and immunocytochemistry. NAPE-PLD(-/-) mice were utilized to
      establish the specificity of probes/antibodies used. The most striking feature of
      NAPE-PLD expression in the brain was in the dentate gyrus, where a strong mRNA
      signal was detected in granule cells. Accordingly, immunocytochemical analysis
      revealed intense NAPE-PLD immunoreactivity in the axons of granule cells (mossy
      fibers). Intense NAPE-PLD immunoreactivity was also detected in axons of the
      vomeronasal nerve that project to the accessory olfactory bulb. NAPE-PLD
      expression was detected in other brain regions (e.g., hippocampus, cortex,
      thalamus, hypothalamus), but the intensity of immunostaining was weaker than in
      mossy fibers. Collectively, the data obtained indicate that NAPE-PLD is expressed
      by specific populations of neurons in the brain and targeted to axonal processes.
      We suggest that NAEs generated by NAPE-PLD in axons may act as anterograde
      synaptic signaling molecules that regulate the activity of postsynaptic neurons.

PMID- 18067140
TI  - Synapses between corticotropin-releasing factor-containing axon terminals and
      dopaminergic neurons in the ventral tegmental area are predominantly
      glutamatergic.
AB  - Interactions between stress and the mesocorticolimbic dopamine (DA) system have
      been suggested from behavioral and electrophysiological studies. Because
      corticotropin-releasing factor (CRF) plays a role in stress responses, we
      investigated possible interactions between neurons containing CRF and those
      producing DA in the ventral tegmental area (VTA). We first investigated the
      cellular distribution of CRF in the VTA by immunolabeling VTA sections with anti
      CRF antibodies and analyzing these sections by electron microscopy. We found CRF
      immunoreactivity present mostly in axon terminals establishing either symmetric
      or asymmetric synapses with VTA dendrites. We established that nearly all CRF
      asymmetric synapses are glutamatergic, insofar as the CRF-immunolabeled axon
      terminals in these synapses coexpressed the vesicular glutamate transporter 2,
      and that the majority of CRF symmetric synapses are GABAergic, insofar as the CRF
      immunolabeled axon terminals in these synapses coexpressed glutamic acid
      decarboxylase, findings that are of functional importance. We then looked for
      synaptic interactions between CRF- and DA-containing neurons, by using antibodies
      against CRF and tyrosine hydroxylase (TH; a marker for DA neurons). We found that
      most synapses between CRF-immunoreactive axon terminals and TH neurons are
      asymmetric (in the majority likely to be glutamatergic) and suggest that
      glutamatergic neurons containing CRF may be part of the neuronal circuitry that
      mediates stress responses involving the mesocorticolimbic DA system. The presence
      of CRF synapses in the VTA offers a mechanism for interactions between the stress
      associated neuropeptide CRF and the mesocorticolimbic DA system.

PMID- 18067141
TI  - Complementary circuits connecting the orbital and medial prefrontal networks with
      the temporal, insular, and opercular cortex in the macaque monkey.
AB  - The origin and termination of axonal connections between the orbital and medial
      prefrontal cortex (OMPFC) and the temporal, insular, and opercular cortex have
      been analyzed with anterograde and retrograde axonal tracers, injected in the
      OMPFC or temporal cortex. The results show that there are two distinct,
      complementary, and reciprocal neural systems, related to the previously defined
      "orbital" and "medial" prefrontal networks. The orbital prefrontal network, which
      includes areas in the central and lateral part of the orbital cortex, is
      connected with vision-related areas in the inferior temporal cortex (especially
      area TEav) and the fundus and ventral bank of the superior temporal sulcus
      (STSf/v), and with somatic sensory-related areas in the frontal operculum (OPf)
      and dysgranular insular area (Id). No connections were found between the orbital
      network and auditory areas. The orbital network is also connected with taste and
      olfactory cortical areas and the perirhinal cortex and appears to be involved in
      assessment of sensory objects, especially food. The medial prefrontal network
      includes areas on the medial surface of the frontal lobe, medial orbital areas,
      and two caudolateral orbital areas. It is connected with the rostral superior
      temporal gyrus (STGr) and the dorsal bank of the superior temporal sulcus (STSd).
      This region is rostral to the auditory parabelt areas, and there are only
      relatively light connections between the auditory areas and the medial network.
      This system, which is also connected with the entorhinal, parahippocampal, and
      cingulate/retrosplenial cortex, may be involved in emotion and other self
      referential processes.

PMID- 18067142
TI  - Difference in migration of placenta according to the location and type of
      placenta previa.
AB  - PURPOSE: To correlate the incidence and rate of placental migration with the mode
      of delivery, pregnancy outcome, and maternal complication according to the
      location (anterior versus posterior) and type of placenta previa (PP). METHODS:
      We prospectively evaluated the placentas of 98 pregnant women with PP or low
      lying placenta (LLP) at the prenatal sonographic examination performed between 20
      and 27 gestational weeks. We divided the pregnant women into groups according to
      type and location of PP. Follow-up sonographic examination was performed between
      32 and 37 weeks. We compared incidence of migration to the normal position and
      calculated the migration rate as the migrated distance divided by the weeks of
      interval between 2 sonographic examinations. We compared the incidences of
      cesarean section, fetal outcome, and maternal complications during the pregnancy.
      RESULTS: The incidence of migration in the group of anterior placentas was
      significantly higher than that in the group of posterior placentas. The mean
      migration rate in the anterior group was 2.6 mm/week, whereas that in the
      posterior group was 1.6 mm/week. The migration rate of incomplete PP was
      significantly higher than that of LLP. Incidence of cesarean section for
      nonmigrated PP was significantly higher in the posterior group. The incidences of
      premature delivery and vaginal spotting were also significantly higher in the
      posterior group. CONCLUSION: Anterior PP and LLP may migrate more often and
      faster than posterior PP. Our results may be useful for planning of prenatal
      management and counseling patients with PP and LLP.

PMID- 18067145
TI  - N-cadherin expression in palisade nerve endings of rat vellus hairs.
AB  - Palisade nerve endings (PNs) are mechanoreceptors around vellus hairs of mammals.
      Each lanceolate nerve ending (LN) of the PN is characterized by a sensory nerve
      ending symmetrically sandwiched by two processes of type II terminal Schwann
      cells (tSCIIs). However, the molecular mechanisms underlying the structural
      organization of the PN are poorly understood. Electron microscopy showed that
      adherens junctions appeared to adhere to the sensory nerve ending and tSCII
      processes, so we examined the location of the N-cadherin adhesion system in PNs
      of rat vellus hairs by using immunoelectron microscopy. N-cadherin localized near
      both ends of the cell boundary between sensory nerve ending and tSCII processes,
      which corresponded to the sites of adherens junctions. We further found cadherin
      associated proteins, alpha- and beta-catenins, at the linings of adherens
      junctions. Three-dimensional reconstruction of immunoelectron microscopic serial
      thin sections showed four linear arrays of N-cadherin arranged longitudinally
      along the LN beneath the four longitudinal borders of two tSCII processes. In
      contrast, sensory nerve fibers just proximal to the LNs formed common
      unmyelinated nerve fibers, in which N-cadherin was located mainly at the mesaxon
      of type I terminal Schwann cells (tSCIs). These results suggest that the four
      linear arrays of N-cadherin-mediated junctions adhere the sensory nerve ending
      and tSCII processes side by side to form the characteristic structure of the LN,
      and the structural differences between the LNs and the proximal unmyelinated
      nerve fibers possibly are due to the difference in the pattern of N-cadherin
      expression between sensory nerve endings and tSCII or tSCI processes.

PMID- 18067146
TI  - Distribution of bursting neurons in the CA1 region and the subiculum of the rat
      hippocampus.
AB  - We performed patch-clamp recordings from morphologically identified and
      anatomically mapped pyramidal neurons of the ventral hippocampus to test the
      hypothesis that bursting neurons are distributed on a gradient from the CA2/CA1
      border (proximal) through the subiculum (distal), with more bursting observed at
      distal locations. We find that the well-defined morphological boundaries between
      the hippocampal subregions CA1 and subiculum do not correspond to abrupt changes
      in electrophysiological properties. Rather, we observed that the percentage of
      bursting neurons is linearly correlated with position in the proximal-distal axis
      across the CA1 and the subiculum, the percentages of bursting neurons being 10%
      near the CA1-CA2 border, 24% at the CA1-subiculum border, and higher than 50% in
      the distal subiculum. The distribution of bursting neurons was paralleled by a
      gradient in afterdepolarization (ADP) amplitude. We also tested the hypothesis
      that there was an association between bursting and two previously described
      morphologically distinct groups of pyramidal neurons (twin and single apical
      dendrites) in the CA1 region. We found no difference in output mode between
      single and twin apical dendrite morphologies, which was consistent with the
      observation that the two morphologies were equally distributed across the
      transverse axis of the CA1 region. Taken together with the known organization of
      connections from CA3 to CA1 and CA1 to subiculum, our results indicate that
      bursting neurons are most likely to be connected to regular spiking neurons and
      vice versa.

PMID- 18067143
TI  - Calcium-fluxing glutamate receptors associated with primary gustatory afferent
      terminals in goldfish (Carassius auratus).
AB  - Presynaptic ionotropic glutamate receptors modulate transmission at primary
      afferent synapses in several glutamatergic systems. To test whether primary
      gustatory afferent fibers express Ca(2+)-permeable AMPA/kainate receptors, we
      utilized kainate-stimulated uptake of Co(2+) along with immunocytochemistry for
      the Ca(2+)-binding proteins (CaBPs) calbindin and calretinin to investigate the
      primary gustatory afferents in goldfish (Carassius auratus). In goldfish, the
      primary gustatory nucleus (equivalent to the gustatory portion of the nucleus of
      the solitary tract) includes the vagal lobe, which is a large, laminated
      structure protruding dorsally from the medulla. Kainate-stimulated uptake of
      Co(2+) (a measure of Ca(2+)-fluxing glutamate receptors) shows punctate staining
      distributed in the distinct laminar pattern matching the layers of termination of
      the primary gustatory afferent fibers. In addition, CaBP immunocytochemistry,
      which correlates highly with expression of Ca(2+)-permeable AMPA/kainate
      receptors, shows a laminar pattern of distribution similar to that found with
      kainate-stimulated cobalt uptake. Nearly all neurons of the vagal gustatory
      ganglion show Co(2+) uptake and are immunopositive for CaBPs. Transection of the
      vagus nerve proximal to the ganglion results in loss of such punctate Co(2+)
      uptake and of punctate CaBP staining as soon as 4 days postlesion. These results
      are consonant with the presence of Ca(2+)-fluxing glutamate receptors on the
      presynaptic terminals of primary gustatory terminals, providing an avenue for
      modulation of primary gustatory input.

PMID- 18067147
TI  - Expression of P2X3 receptor in the trigeminal sensory nuclei of the rat.
AB  - Trigeminal primary afferents expressing P2X(3) receptor are involved in the
      transmission of orofacial nociceptive information. However, little is known about
      their central projection pattern and ultrastructural features within the
      trigeminal brainstem sensory nuclei (TBSN). Here we use multiple
      immunofluorescence and electron microscopy to characterize the P2X(3)
      immunopositive (+) neurons in the trigeminal ganglion and describe the
      distribution and synaptic organization of their central terminals within the rat
      TBSN, including nuclei principalis (Vp), oralis (Vo), interpolaris (Vi), and
      caudalis (Vc). In the trigeminal ganglion, P2X(3) immunoreactivity was mainly in
      small and medium-sized somata, but also frequently in large somata. Although most
      P2X(3) (+) somata costained for the nonpeptidergic marker IB4, few costained for
      the peptidergic marker substance P. Most P2X(3) (+) fibers in the sensory root of
      trigeminal ganglion (92.9%) were unmyelinated, whereas the rest were small
      myelinated. In the TBSN, P2X(3) immunoreactivity was dispersed in the rostral
      TBSN but was dense in the superficial laminae of Vc, especially in the inner
      lamina II. The P2X(3) (+) terminals contained numerous clear, round vesicles and
      sparse large, dense-core vesicles. Typically, they were presynaptic to one or two
      dendritic shafts and also frequently postsynaptic to axonal endings, containing
      pleomorphic vesicles. Such P2X(3) (+) terminals, showing glomerular shape and
      complex synaptic relationships, and those exhibiting axoaxonic contacts, were
      more frequently seen in Vp than in any other TBSN. These results suggest that
      orofacial nociceptive information may be transmitted via P2X(3) (+) afferents to
      all TBSN and that it may be processed differently in different TBSN.

PMID- 18067148
TI  - Organization of connectivity of the rat presubiculum: II. Associational and
      commissural connections.
AB  - The regional, laminar, and longitudinal organization of intrinsic projections in
      the presubiculum was examined in the rat with the retrograde tracer horseradish
      peroxidase conjugated to wheat germ agglutinin and the anterograde tracer
      Phaseolus vulgaris-leucoagglutinin. Cells of origin of intrinsic projections in
      the presubiculum were distributed in layers II and V, with almost none in layers
      III and VI. Projections from layer II cells were bilateral and confined to layers
      II and V and also to the deep portion of layer I, whereas projections from layer
      V cells were ipsilateral and confined largely to layer V, with fewer projections
      to layer II. Septotemporal and proximodistal differences in both the projection
      and the distribution of layer II cells were found: layer II cells in the septal
      and mid presubiculum, especially those located in the distal part, provided long
      projections to the temporal presubiculum, whereas layer II cells in the temporal
      presubiculum provided slightly shorter projections almost entirely within the mid
      and temporal presubiculum. Layer II cells aggregated massively in the distal
      portions of the septal and mid presubiculum, but very few layer II cells were
      found in the most proximal part, especially in the temporal presubiculum. On the
      other hand, in layer V, cells of origin and their terminals were diffusely and
      equally distributed throughout the entire proximodistal extent of the
      presubiculum. Layer V cells did not project longitudinally as far as layer II
      cells. These longitudinal connections, in layers II and V, make it possible to
      merge information conveyed by parallel pathways in the presubiculum.

PMID- 18067149
TI  - Heterogeneous expression of gamma-aminobutyric acid and gamma-aminobutyric acid
      associated receptors and transporters in the rat suprachiasmatic nucleus.
AB  - The hypothalamic suprachiasmatic nucleus (SCN) is the primary mammalian circadian
      clock that regulates rhythmic physiology and behavior. The SCN is composed of a
      diverse set of neurons arranged in a tight intrinsic network. In the rat,
      vasoactive intestinal peptide (VIP)- and gastrin-releasing peptide (GRP)
      containing neurons are the dominant cell phenotypes of the ventral SCN, and these
      cells receive photic information from the retina and the intergeniculate leaflet.
      Neurons expressing vasopressin (VP) are concentrated in the dorsal and medial
      aspects of the SCN. Although the VIP/GRP and VP cell groups are concentrated in
      different regions of the SCN, the separation of these cell groups is not
      absolute. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is
      expressed in most SCN neurons irrespective of their location or peptidergic
      phenotype. In the present study, immunoperoxidase labeling, immunofluorescence
      confocal microscopy, and ultrastructural immunocytochemistry were used to examine
      the spatial distribution of several markers associated with SCN GABAergic
      neurons. Glutamate decarboxylase, a marker of GABA synthesis, and vesicular GABA
      transporter were more prominently observed in the ventral SCN. KCC2, a K(+)/Cl(-)
      cotransporter, was highly expressed in the ventral SCN in association with VIP-
      and GRP-producing neurons, whereas VP neurons in the dorsal SCN were devoid of
      KCC2. On the other hand, GABA(B) receptors were observed predominantly in VPergic
      neurons dorsally, whereas, in the ventral SCN, GABA(B) receptors were associated
      almost exclusively with retinal afferent fibers and terminals. The differential
      expression of GABAergic markers within the SCN suggests that GABA may play
      dissimilar roles in different SCN neuronal phenotypes.

PMID- 18067150
TI  - Neuroendocrine secretory protein 55 (NESP55) in the spinal cord of rat: an
      immunocytochemical study.
AB  - The immunohistochemical expression of a novel chromogranin-like protein,
      neuroendocrine secretory protein 55 (NESP55), in the rat spinal cord was
      investigated. NESP55-immunoreactive cells were detected in the ventral horn,
      intermediate laminae, and deep dorsal horn, comprising motoneurons, autonomic
      neurons, and interneurons throughout all spinal segments. Within laminae I-II of
      the dorsal horn, one or two NESP55-positive cells were often seen. Nerve fibers
      also contained NESP55 immunoreactivity (IR) and were particularly prominent in
      the ventral horn. No nerve terminals/varicosities appeared to contain NESP55 in
      any spinal lamina. Double-staining experiments revealed that a high proportion of
      the NESP55-positive neurons were cholinergic. Moreover, NESP55-IR in the
      motoneurons was evenly distributed in the whole cytoplasm with a finely granular
      appearance. In contrast, the fluorescent material in the preganglionic neurons
      was concentrated in the perinuclear region and largely overlapped with the trans
      Golgi network marker TGN38. Our data provide detailed morphological information
      on the distribution of NESP55-IR in the rat spinal cord. Also, the differential
      intracellular expression of NESP55-IR in the spinal motoneurons and autonomic
      neurons suggests that NESP55 may be processed into different secretory granules
      and may be involved in both constitutive and regulated pathways in these neurons.

PMID- 18067151
TI  - Atypical expression of Drosophila gustatory receptor genes in sensory and central
      neurons.
AB  - Members of the Drosophila gustatory receptor (Gr) gene family are generally
      expressed in chemosensory neurons and are known to mediate the perception of
      sugars, bitter substrates, CO(2), and pheromones. The Gr gene family consists of
      68 members, many of which are organized in gene clusters of up to six genes, yet
      only expression of about 15 Gr genes has been characterized in detail prior to
      this study. Here we describe the first comprehensive expression analysis of six
      highly conserved Gr genes, Gr28a and Gr28b.a to Gr28b.e. Four of these Gr genes
      are not only expressed in the characteristic pattern associated with previously
      analyzed Gr genes-chemosensory neurons of the gustatory and olfactory system-but
      several other types of sensory neurons and neurons in the brain. Specifically, we
      show that several of the Gr28 genes are expressed in abdominal multidendritic
      neurons, putative hygroreceptive neurons of the arista, neurons associated with
      the Johnston's organ, peripheral proprioceptive neurons in the legs, neurons in
      the larval and adult brain, and oenocytes. Thus, our findings suggest that some
      Gr genes are utilized in nongustatory roles in the nervous system and tissues
      involved in proprioception, hygroreception, and other sensory modalities. It is
      also possible that the Gr28 genes have chemosensory roles in the detection of
      internal ligands.

PMID- 18067152
TI  - Ultrastructural evidence for pre- and postsynaptic localization of Cav1.2 L-type
      Ca2+ channels in the rat hippocampus.
AB  - In the hippocampal formation, Ca(v)1.2 (L-type) voltage-gated Ca(2+) channels
      mediate Ca(2+) signals that can trigger long-term alterations in synaptic
      efficacy underlying learning and memory. Immunocytochemical studies indicate that
      Ca(v)1.2 channels are localized mainly in the soma and proximal dendrites of
      hippocampal pyramidal neurons, but electrophysiological data suggest a broader
      distribution of these channels. To define the subcellular substrates underlying
      Ca(v)1.2 Ca(2+) signals, we analyzed the localization of Ca(v)1.2 in the
      hippocampal formation by using antibodies against the pore-forming alpha(1)
      subunit of Ca(v)1.2 (alpha(1)1.2). By light microscopy, alpha(1)1.2-like
      immunoreactivity (alpha(1)1.2-IR) was detected in pyramidal cell soma and
      dendritic fields of areas CA1-CA3 and in granule cell soma and fibers in the
      dentate gyrus. At the electron microscopic level, alpha(1)1.2-IR was localized in
      dendrites, but also in axons, axon terminals, and glial processes in all
      hippocampal subfields. Plasmalemmal immunogold particles representing alpha(1)1.2
      IR were more significant for small- than large-caliber dendrites and were largely
      associated with extrasynaptic regions in dendritic spines and axon terminals.
      These findings provide the first detailed ultrastructural analysis of Ca(v)1.2
      localization in the brain and support functionally diverse roles of these
      channels in the hippocampal formation.

PMID- 18067153
TI  - Design, synthesis, conformational and membrane ion transport studies of proline
      adamantane hybrid cyclic depsipeptides.
AB  - The design, synthesis, conformational, crystallographic, and ion transport
      studies of 30-membered, proline containing depsipeptides that incorporate the
      rigid low molecular weight lipophilic adamantane (Adm) building blocks are
      reported. The adamantyl groups provide the desired membrane permeability and
      conformational constraint for efficient transport in lipid membranes. The novel
      cyclic depsipeptides are: c[--Adm--C(O)--Pro-- O--CH(2)-- CHR--NH--C(O)--Pro-
      C(O)-- Adm--C(O)--Pro--C(O)--NH--CHR--CH(2)-- O--Pro--C(O)--] where R==H for A
      and R==CONH--Adm for B. Crystal structure analysis of A established that the two
      peptide segments are identical in formula and in conformation and that the
      peptides are bonded to the interleaving Adm at the 1 and 3 positions. However,
      the complete ring is highly asymmetric in shape since bonds for both Peptide-Adm
      Peptide segments have the syn-anti motif. Torsional angles for the connecting
      bonds to Adm are -162 degrees , +71 degrees and -169 degrees , -48 degrees . The
      irregular clamshell shape of the molecule has three internal C==O moieties
      directed in a manner that could provide three Na(+)--O ligands. While A exhibited
      negligible transport of Na(+) ions across membranes, peptide B endowed with two
      additional adamantanes in the periphery did transport Na(+) ions from outside to
      inside.

PMID- 18067154
TI  - Conformational change from antiparallel beta-sheet to alpha-helix in a series of
      depsipeptide, -(Leu-Leu-Lac)(n)-: syntheses, spectroscopic studies, and crystal
      structures of Boc-Leu-Lac-OEt and Boc-(Leu-Leu-Lac)(n)-OEt (n = 1, 2).
AB  - The depsipeptides Boc-Leu-Lac-OEt (1) and Boc-(Leu-Leu-Lac)(n)-OEt (n = 1, 2) (2
      and 3, respectively) (Boc = tert-butyloxycarbonyl, Lac = L-lactic acid residue)
      has been synthesized and studied by crystallographic, CD spectroscopic, and ESI
      MS analyses. In the packing cells, those three compounds adopt beta-strand
      conformations. Each molecule is linked into a dimer (1) or an infinite assembly
      (2 and 3) by tight hydrogen bonds of the type NH...O==C. Interestingly, the
      hexamer, 3 shows the first example of antiparallel pleated beta-sheet crystal
      structure for a depsipeptide molecule. In the packing cells, especially for 3,
      the ester groups O--C==O are perpendicularly oriented to the amide groups NH-
      C==O and beta-sheet planes to avoid the interaction between --O--(ester) and
      O==C. Therefore, when the chain length become longer, the O...O==C repulsion
      interaction works as a beta-sheet breaker and hence promotes an alpha-helical
      structure as observed for Boc-(Leu-Leu-Lac)(3)-Leu-Leu-OEt (4) (Oku et al.
      Biopolymers 2004, 75, 242-254) and Boc-(Leu-Leu-Lac)(n)-OEt (n = 4-6) (5-7)
      (Katakai et al., Biopolymers 1996, 38, 285-290), in which the O...O==C repulsion
      does not cause significant structural changes in alpha-helical main chains.
      Therefore from the structural and spectroscopic analyses, we have found governing
      factors for the specificity in the beta-sheet and alpha-helix decision in this
      series of depsipeptides, -(Leu-Leu-Lac)(n)-.

PMID- 18067155
TI  - Conformational transition and liquid crystalline state of regenerated silk
      fibroin in water.
AB  - The conformational transition of molecular chains of regenerated silk fibroin
      (SF) aqueous solution is systematically investigated by circular dichroism,
      Raman, IR, and UV-vis spectroscopies. It is found that an initial random coil
      conformation of the SF can be readily changed into an ordered beta-sheet
      structure by optimizing the solution conditions, such as the SF concentration,
      pH, temperature, or metal-ion content. Circular dichroic spectra quantitatively
      confirm a steadily decreased content of the random coil conformation but a
      significantly increased beta-sheet content after an ultrasonic or extruding
      treatment. Furthermore, the extrusion is more powerful to achieve high beta-sheet
      content than the ultrasonic. It is interesting that the polarized optical
      micrographs of the SF aqueous solution extruded by injection illustrate the
      formation and existence of liquid crystalline state. A study of extrusion in
      vitro could be used as a model system to understand the natural silk spinning
      process in silkworm.

PMID- 18067156
TI  - Increased PFK activity and GLUT4 protein content in McArdle's disease.
AB  - Inborn errors of metabolism represent an opportunity to conduct studies in order
      to understand compensatory adaptations to a defective metabolic pathway. We
      evaluated the molecular and biochemical adaptations in substrate metabolism
      (glycolysis, electron transport chain, tricarboxylic acid cycle, beta-oxidation)
      in response to myophosphorylase deficiency in skeletal muscle from 13 patients
      with McArdle's disease (MD) and 13 age-matched controls. MD muscle had higher
      phosphofructokinase protein content and activity as well as glucose transporter 4
      (GLUT4) protein content and lower GLUT4 mRNA content than controls. At the
      protein level, skeletal muscle adaptations suggest an augmented glucose transport
      and glycolytic flux as a compensatory metabolic strategy to a chronic absence of
      muscle glycogen phosphorylase. These results support previous findings of
      increased glucose uptake during exercise and alleviation of symptoms with oral
      sucrose in patients with MD.

PMID- 18067157
TI  - Effect of surface chemistry modification of functional gold nanoparticles on the
      drug accumulation of cancer cells.
AB  - In this report, we have explored the possibility to facilitate the drug delivery
      efficiency for cancer cells through the surface chemistry modification of gold
      nanoparticles (AuNPs), where the functional AuNPs were synthesized by the ligand
      exchange reaction between triphenyl phosphide-stabilized precursor nanoparticles
      and mercaptopropionic acid. Our observations demonstrate that the combination of
      the anticancer drug daunorubicin with relevant AuNPs could be used as an
      efficient way to mark the cancer cells, which may afford the potential
      application for the early diagnosis of the respective cancers. Besides, the
      synergistic enhanced effect of the relevant gold nanoparticles on the drug uptake
      of target cancer cells could provide a new strategy to inhibit the multidrug
      resistance of the respective cancers.

PMID- 18067158
TI  - Growth, viability, adhesion potential, and fibronectin expression in fibroblasts
      cultured on zirconia or feldspatic ceramics in vitro.
AB  - Zirconia, a biomaterial widely used in dentistry, has recently attracted much
      attention for its mechanical strength and toughness. Previously, its lack of
      mutagenic and carcinogenic power was reported. We describe here other essential
      aspects to be taken into account to define in vitro the biocompatibility of a
      material: the growth rate, viability, and adhesion capacity of normal stabilized
      cells growing on it. To this aim, immortalized RAT-1 fibroblasts, growing either
      on zirconia and on feldspatic (FE) ceramics were compared. In particular, the
      level of expression and the intra- and extra-cellular organization of
      fibronectin, a glycoprotein involved in cellular adhesion and migration during
      tissue repair, was analyzed. Fibroblasts cultured on zirconia showed a higher
      growth rate, and underwent necrosis at lower levels than cells on FE ceramic,
      whereas either materials did not stimulate apoptosis. Adhesion capacity of
      fibroblasts was evaluated measuring adherent cell nucleic acids with the
      fluorimetric CyQuant assay, and it was found significantly higher in cells
      cultured on zirconia than on FE ceramic. This finding may be explained by the
      higher and more precocious expression of the adhesion protein fibronectin
      observed by indirect immunofluorescence in fibroblasts on zirconia. Overall, the
      results suggest that zirconia, exerting low cytotoxicity and strongly inducing
      adhesion capacity, increases cellular growth rate of fibroblasts. All these
      features suggest that zirconia could represent a more suitable biomaterial than
      FE ceramic for prosthesis in dentistry.

PMID- 18067159
TI  - Fabrication of fast responsive, thermosensitive poly(N-isopropylacrylamide)
      hydrogels by using diethyl ether as precipitation agent.
AB  - An effective strategy was developed and demonstrated to improve the properties of
      thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel by using diethyl
      ether as a precipitation agent during the polymerization/crosslinking. Results
      reveal that the modified PNIPAAm hydrogels have the heterogeneous network
      structures and decreased LCSTs in a comparison with the normal PNIPAAm hydrogel.
      The modified PNIPAAm hydrogels also exhibit significantly improved sensitive
      properties, including fast response and stable, rapid, large magnitude
      oscillatory shrinking-swelling upon temperature cycles around lower critical
      solution temperature. In addition, fish DNA, used as a model drug, is loaded into
      the modified PNIPAAm hydrogels, the controlled release behaviors of the drug
      loaded hydrogels at different temperatures (22 and 37 degrees C) are further
      examined.

PMID- 18067160
TI  - Polymer cell culture substrates with micropatterned carbon nanotubes.
AB  - This article presents study of the interactions between cells and micropatterned
      carbon nanotubes on a polymer cell culture substrate. The polymer substrates with
      patterned carbon nanotubes were fabricated using an imprint process, whereby the
      nanotubes were pressed into a polymer layer at high temperature. The patterned
      substrates featured 28 different nanotube patterns of microscale lanes and
      circles, where the feature sizes ranged from 9 to 76 microm. Osteoblast-like
      cells were seeded on the substrates and cell alignment was quantified via
      fluorescent and electron microscopy. Many patterns were fabricated on each
      polymer substrate, allowing 28 different experiments on each cell culture
      substrate, which were tested over 10,000 cells. The cell response to the
      patterned nanotubes showed a maximum alignment to the microlane patterns of 55 +/
      6% and no significant alignment to microcircle patterns. This work enables the
      study of cell response to a wider range of patterns featuring both the micro and
      nano length scales.

PMID- 18067161
TI  - One-step preparation of poly(epsilon-caprolactone)-poly(ethylene glycol)
      poly(epsilon-caprolactone) nanoparticles for plasmid DNA delivery.
AB  - In this article, a kind of biodegradable poly(epsilon-caprolactone)-Poly(ethylene
      glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) copolymer was synthesized
      by ring-opening polymerization method. The PCEC nanoparticles were prepared at
      one-step by modified emulsion solvent evaporation method using CTAB as
      stabilizer. With increase in PCEC concentration, the particle size increased
      obviously, but zeta potential only increased slightly. The obtained cationic PCEC
      nanoparticle was employed to condense and adsorb DNA onto its surface. Plasmid
      GFP (pGFP) was used as model plasmid to evaluate the loading capacity of cationic
      PCEC nanoparticles in this work. The DNA/nanoparticles weight ratio at 1:16
      induced almost neutral zeta potential of DNA-nanoparticles complex. At this time,
      the size of complex became abnormally large which implied aggregates formed. So
      DNA-nanoparticles weight ratio should be chosen carefully. The cationic PCEC
      nanoparticles had the capacity of condensing plasmid DNA into complex when the
      DNA/nanoparticles weight ratio was lower than 1:8, which was evidenced by gel
      retardation assay. In vitro release behavior of DNA/nanoparticle complexes was
      also studied here. The obtained cationic PCEC nanoparticles might have great
      potential application in DNA delivery.

PMID- 18067162
TI  - Supramolecular hydrogels based on inclusion complexation between poly(ethylene
      oxide)-b-poly (epsilon-caprolactone) diblock copolymer and alpha-cyclodextrin and
      their controlled release property.
AB  - Supramolecular hydrogels formed through inclusion complexation between high
      molecular weight poly(ethylene oxide) (PEO) and alpha-cyclodextrin (alpha-CD)
      showed the most sustained release kinetics in vitro with molecular weight of PEO
      of 35,000 within 5 days. To improve the sustained release and overcome using high
      molecular weight PEO, novel supramolecular hydrogels have been prepared by using
      biodegradable amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO
      PCL) diblock copolymer instead of PEO. Rheologic studies indicate that the
      prepared hydrogel is thixotropic and reversible. The in vitro release kinetics of
      hydrogels has been studied by using fluorescein isothiocyanate labeled dextran
      (dextran-FITC) as model drug. Compared with that of alpha-CD/PEO supramolecular
      hydrogels, the sustained release of alpha-CD/PEO-PCL supramolecular hydrogel was
      increased significantly even if with much lower molecular weight of PEO block.
      This result indicates incorporating hydrophobic PCL block could reduce the
      molecular weight of PEO required for long-term drug release system. The sustained
      release is also dependent on the alpha-CD content in supramolecular hydrogels.
      Thus, the properties of supramolecular hydrogel can be fine-tuned with different
      polymer and at different alpha-CD content, opening a wide range of applications.

PMID- 18067163
TI  - Histological analysis of induced cartilage on the biodegradable or
      nonbiodegradable membranes from immature muscular tissue in vitro.
AB  - Successful tissue engineering relies on a combination of cells, cytokines, and
      appropriate scaffolds. Here, we tried to induce the formation of cartilage in
      vitro using immature muscular tissue, crude bone morphogenetic protein (BMP) as a
      source of the cytokine, and biodegradable membranes (BioMend; BM and GC-membrane;
      GC-M) or a nonbiodegradable membrane (GORE-TEX; GT) as scaffolds. Crude BMP was
      extracted from bovine cortical bones, dried, and dissolved in 1M urea before it
      was added to immature muscular tissue from the forelimbs of fetal Sprague Dawley
      rats at 20 days of pregnancy. The tissue was then cultured for 2 weeks in a
      carbon dioxide incubator. Complete cartilage was observed only when GT was used
      as a scaffold. In addition, cartilage-like tissue formation was observed when BM
      was used, and partial cartilage formation was observed for GC-M. Therefore, these
      results show that immature muscular tissue differentiated into cartilage and GORE
      TEX is the most effective material for use as a scaffold in this model of tissue
      engineering.

PMID- 18067164
TI  - Evaluation of the skin sensitizing potential of biodegradable magnesium alloys.
AB  - Corroding metals made of magnesium alloys represent a new class of degradable
      implants for musculoskeletal surgery. These implants may be associated with skin
      sensitizing reactions because of the release of metal ions. This study was
      conducted to compare the sensitizing potential of four different magnesium alloys
      (AZ31, AZ91, WE43, and LAE442) to current implant materials such as titanium
      (TiAl6V4) and a degradable polymer (SR-PLA96). Solutions and solid chips of these
      materials were prepared and tested in 156 guinea pigs according to the Magnusson
      Kligman test. A standard allergen (hydroxy-cinnamon-aldehyde) causing allergic
      erythema was used as positive control and a standard irritant (sodium-lauryl
      sulfate) causing local skin irritation for less than 24 h was used as negative
      control. All erythema were graded immediately and 24 h after patch removal by
      three independent observers. Histomorphological analyses were performed on skin
      biopsies taken 24 h after patch removal. We found that initial erythema in
      animals treated with solid chips diminished within 24 h and were caused by local
      skin irritation. Local skin irritation was also determined in erythema remaining
      for 24 h after patch removal in animals treated with dissolved test materials. No
      allergenic reactions according to the histomorphological criteria were observed
      in skin biopsies. We conclude that no skin sensitizing potential were detected
      for standard materials as well as for all tested magnesium alloys by the used
      methods.

PMID- 18067165
TI  - Collagen release kinetics of surface functionalized 45S5 Bioglass-based porous
      scaffolds.
AB  - A highly interconnected porous scaffold made from 45S5 Bioglass was fabricated by
      the polymer replica technique and surface functionalized for protein
      immobilization. Subsequently rat-tail collagen type I was immobilized on the
      scaffolds. The protein and ion release rates were determined by UV-vis
      spectroscopy and ion chromatography, respectively, and the impact on
      hydroxyapatite (HA) formation on the scaffolds upon immersion in SBF was
      evaluated. It was discovered that the surface functionalization enhanced the
      stability of the collagen attachment and stability against the increment of pH in
      a biological environment, resulting in similar collagen release kinetics in
      solutions of different pH values. Without the surface modification, collagen
      release was considerably expedited by the increment of pH in a surrounding
      solution. It was also found that the collagen immobilization does not effect the
      formation of carbonated HA on the scaffold surface. The stable collagen
      attachment to the functionalized scaffold makes this approach potentially
      suitable for improving cell attachment and thus for enhancing the application
      potential of the scaffold in tissue engineering.

PMID- 18067166
TI  - Vascularization and biocompatibility of scaffolds consisting of different calcium
      phosphate compounds.
AB  - Scaffolds for tissue engineering of bone should mimic bone matrix and promote
      vascular ingrowth. Whether synthetic hydroxyapatite and acellular dentin, both
      materials composed from calcium phosphate, fulfill these material properties has
      not been studied yet. Therefore, we herein studied in vivo the host angiogenic
      and inflammatory response to these biomaterials. Porous scaffolds of
      hydroxyapatite and isogeneic acellular dentin were implanted into the dorsal
      skinfold chamber of balb/c mice. Additional animals received perforated implants
      of isogeneic calvarial bone displaying pores similar in size and structure to
      those of both scaffolds. Chambers of animals without implants served as controls.
      Angiogenesis and neovascularization as well as inflammatory leukocyte-endothelial
      cell interaction and microvascular leakage were analyzed over a 14-day time
      period using intravital fluorescence microscopy. Implantation of both
      hydroxyapatite and dentin scaffolds showed a slight increase in leukocyte
      recruitment compared with controls. This was associated with an elevation of
      microvascular permeability, which was comparable to that observed in response to
      isogeneic bone. In addition, hydroxyapatite as well as dentin scaffolds induced a
      marked angiogenic response, which resulted in complete vascularization of the
      implants until day 14. Of interest, in hydroxyapatite scaffolds, the newly formed
      capillaries were not as densely meshed as in dentin scaffolds, in which the
      functional capillary density was comparable to that measured in bone implants.
      Hydroxyapatite and, in particular, dentin scaffolds promote vascularization and
      exhibit a biocompatibility comparable to that of isogeneic bone. This may
      guarantee the rapid incorporation of these materials into the host tissue.

PMID- 18067167
TI  - A novel scaffold based on formation and agglomeration of PCL microbeads by freeze
      drying.
AB  - Polycaprolactone (PCL) scaffolds were prepared by freeze-drying of polymer
      solutions in tetrahydrofuran. Effects of the polymer composition, which is 10 and
      20% (w/v), on the scaffold properties for example, morphology, porosity,
      mechanical stability, degradability, and so forth were investigated by using
      suitable methods. Scanning electron microscopy photographs clearly showed the
      presence of a porous, three-dimensional structure including agglomerated PCL
      microspheres. Porosity analysis demonstrated that 10 and 20% (w/v) scaffolds have
      95.9% and 74.4% porosity, respectively. The microspheres have very narrow size
      distribution and their diameters increase from 50-70 microm to 90-100 microm with
      increasing PCL content from 10 to 20% (w/v). The microspheres were highly
      connected with each other and the scaffolds have superior mechanical properties
      when compared with the traditional PCL scaffolds. Cell culture experiments showed
      that periodontal ligament cells (PDL) were able to attach and proliferate on the
      20% PCL scaffold. The results demonstrated that this novel PCL structure will be
      a potential tissue engineering scaffold with its superior properties and simple
      preparation procedure.

PMID- 18067168
TI  - Magnetic nanoparticles for improving cell invasion in tissue engineering.
AB  - It has been widely recognized that cells are seeded onto only the superficial
      layer of three-dimensional (3D) scaffolds in tissue engineering technology. This
      leads to tissue necrosis that occurs in the central part of 3D scaffolds. To
      solve this issue, an effective cell seeding technique into the central part of 3D
      scaffolds is required. Chitosan has characteristics of biocompatibility,
      biodegradability, and low-toxicity. In this study, we developed novel magnetic
      nanoparticles (MNs) coated with chitosan for enhancing cellular invasion using
      magnetic force. Cell-invasion efficiency was enhanced by introducing our novel
      MNs into cells and by the presence of magnetic force. This invasion efficacy
      depends on the degree of magnetic force. Matrix metalloproteinases and adhesion
      molecules that were upregulated in response to the attached nanoparticles and
      exposure to a magnetic force may also play a crucial role in improving cell
      invasive ability in this system. This current system can efficiently enhance cell
      seeding into the depth of the scaffold, increase subsequent cell-cell
      interactions and shorten the period of cell proliferation. This system is thought
      to be useful in the development of cell-based strategies for the repair or
      replacement of tissue and other novel therapies.

PMID- 18067169
TI  - Therapeutic doses of radiation alter proliferation and attachment of osteoblasts
      to implant surfaces.
AB  - Osseointegration of implants in irradiated bone is inadequate. The effect of
      radiation on cell-implant material interaction has not been adequately studied.
      The goal of this study was to investigate the effects of ionizing radiationon the
      proliferation, differentiation, and attachment of osteoblasts to commercially
      pure titanium (cpTi). Human fetal osteoblasts (hFOB) were irradiated either
      before or after plating in tissue culture (TC) dishes with or without cpTi disks.
      Radiation was single dose of 10 cGy, 25 cGy, 50 cGy, 1 Gy, 2 Gy, 4 Gy or 8 Gy.
      Cell proliferation was determined by counting trypsinized cells on 7 days after
      irradiation. Attachment of irradiated hFOB was measured indirectly by counting
      cells 2 and 6 h after plating. Differentiation was evaluated by alkaline
      phosphatase activity. Compared with nonirradiated sham controls, higher doses of
      radiation significantly reduced cell attachment and proliferation. Both
      proliferation and attachment were significantly lower on cpTi compared with TC.
      Attachment decreased based on the length of postirradiation period. Although
      differentiation was significantly enhanced by a dose of 8 Gy, proliferation was
      lowest. These initial studies show that effects of therapeutic doses of radiation
      on osteoblasts varied depending on the surface, time-elapsed, and amount of
      radiation.

PMID- 18067170
TI  - Interaction of glycopolymers with human hematopoietic cells from cord blood and
      peripheral blood.
AB  - Polystyrene derivatives, poly[N-pvinylbenzyl-O-D-glucopyranosyl-(1-4)-D
      glucoamide] (PV Maltose) and poly[N-p-vinylbenzyl-O-mannopyranosyl-(1-4)-D
      glucoamide] (PV Mannose), which contain glucose and mannose moieties,
      respectively, have the specific binding ability with murine hematopoietic cells.
      In this study, we confirm the ability of these glycopolymers to interact
      specifically with human hematopoietic stem cells (HSCs) and mature cells derived
      from human cord blood (CB) and peripheral blood (PB). Using fluorescence
      isothiocyanate (FITC)-labeled glycopolymers, we observed that 98% to 93% of
      hematopoietic cells interacted very strongly with PV Mannose, and 63% of CB and
      29% PB interacted with PV Maltose. Both glycopolymers bound better to cells from
      CB than from PB. Cytotoxic studies revealed that a 0.1 mM dose of PV Mannose
      induced apoptosis in 20% CB cells, in contrast to 3-5% PB cells. Furthermore, we
      demonstrated that all of CD34(+) HSCs of both origins bound specifically to PV
      Mannose, whereas 33-47% bound to PV Maltose. In addition, the majority of B cells
      (CD19(+)), T cells (CD3(+)), monocytes (CD14(+)), and erythrocytes (CD235a(+))
      bound to PV Mannose, but a lower percentage interacted with PV Maltose. In vivo
      study, bone marrow, spleen, and liver tissues in NOD-SCID mice injected with PV
      Mannose conjugated CB, were detected PV Mannose positive hematopoietic cells.
      These data suggest that the use of PV Mannose and PV Maltose might be used for
      gene and drug delivery for hematopoietic cells and thus, may be useful in
      therapeutic settings.

PMID- 18067171
TI  - Regeneration of dentin-pulp complex with cementum and periodontal ligament
      formation using dental bud cells in gelatin-chondroitin-hyaluronan tri-copolymer
      scaffold in swine.
AB  - The purpose of this study is to use a tissue engineering approach for tooth
      regeneration. The swine dental bud cells (DBCs) were isolated from the developing
      mandibular teeth, expanded in vitro, and cultured onto cylinder scaffold gelatin
      chrondroitin-hyaluronan-tri-copolymer (GCHT). After culturing in vitro, the
      DBCs/GCHT scaffold was autografted back into the original alveolar socket.
      Hematoxylin and eosin (H&E) staining combined with immunohistochemical staining
      were applied for identification of regenerated tooth structure. After 36-week
      post-transplantation, tooth-like structures, including well-organized dentin-pulp
      complex, cementum, and periodontal ligament, were evident in situ in two of six
      experimental animals. The size of the tooth structure (1 x 0.5 x 0.5 cm(3) and
      0.5 x 0.5 x 0.5 cm(3) size) appeared to be dictated by the size of the GCHT
      scaffold (1 x 1 x 1.5 cm(3)). The third swine was demonstrated with irregular
      dentin-bony like calcified tissue about 1 cm in diameter without organized tooth
      or periodontal ligament formation. The other three swine in the experimental
      group showed normal bone formation and no tooth regeneration in the
      transplantation sites. The successful rate of tooth regeneration from DBCs/GCHT
      scaffolds' was about 33.3%. In the control group, three swine's molar teeth buds
      were removed without DBCs/GCHT implantation, the other three swine received GCHT
      scaffold implants without DBCs. After evaluation, no regenerated tooth was found
      in the transplantation site of the control group. The current results using
      DBSs/GCHT scaffold autotransplantation suggest a technical breakthrough for tooth
      regeneration.

PMID- 18067172
TI  - Immobilized cytokines as biomaterials for manufacturing immune cell based
      vaccines.
AB  - Manufacturing of bioactive cell culture substrates represents a major challenge
      for the development of cell therapy for tissue repair and immune treatment of
      cancers, infectious diseases, or immunodeficiencies. In this context, we
      evaluated the capacity of several differentiation factors, including Granulocyte
      Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating
      Factor (M-CSF), to drive differentiation of primary cell cultures, once
      immobilized on surfaces. We show that covalently immobilized signal factors fully
      retain their biological properties and efficiently promote differentiation of
      mouse and/or human precursor cells leading to the production of dendritic cells
      and macrophages. For GM-CSF, we also show that the efficiency of receptor
      signaling is comparable using either soluble or tethered molecules. Such
      artificial bioactive interfaces are suitable for the development and automated
      production of cell-based vaccines and therapies.

PMID- 18067174
TI  - Concurrent hemichorea and migrainous aura--a perfusion study on the basal ganglia
      using xenon-computed tomography.
AB  - A variety of etiologies underlie the neurophysiological imbalance resulting in
      chorea. We report a 57-year-old woman with a long-history of migraine who
      suddenly experienced concurrent scintillating scotoma and rapid involuntary
      movement of her neck and right extremities. Diffusion-weighted magnetic resonance
      imaging (MRI) failed to detect any fresh ischemic and/or hemorrhagic lesions.
      Xenon-computed tomography (CT) disclosed gross reduction in the cerebral blood
      flow (CBF) of the left occipital area. With precise mapping to the brain atlas,
      extreme hyperperfusion in the motor thalamus was found on the left side.
      Asymmetrical CBF reduction of the left subthalamic nucleus was also noted. Her
      symptoms gradually improved and completely disappeared within 15 days. Repeated
      xenon-CT 1 month post-onset demonstrated normalized CBF in the affected areas.
      Our study suggests that vascular event underlies the migrainous aura in this case
      and secondarily provokes a loss of inhibitory control of the motor thalamus
      resulting in the manifestation of hemichorea.

PMID- 18067173
TI  - Association of olfactory dysfunction with risk for future Parkinson's disease.
AB  - OBJECTIVE: Although olfactory dysfunction is commonly associated with Parkinson's
      disease (PD), it is not known whether such dysfunction can predate the onset of
      clinical PD in a community-based population. This study examines the association
      of olfactory dysfunction with future development of PD in Honolulu-Asia Aging
      Study cohort members METHODS: Olfaction was assessed from 1991 to 1996 in 2,267
      men in the Honolulu-Asia Aging Study aged 71 to 95 years who were free of
      clinical PD and dementia at the time of olfaction testing. Participants were
      followed for up to 8 years for incident PD RESULTS: In the course of follow-up,
      35 men were diagnosed with PD (24.6/10,000 person-years). The average age at the
      time of diagnosis was 82.9 +/- 3.8 (range, 76-93) years, and the average time to
      a diagnosis was 4.0 +/- 1.9 (range, 1-8) years. During the first 4 years of
      follow-up, age-adjusted incidence of PD declined from 54.5/10,000 person-years in
      the lowest quartile of odor identification to 26.6, 8.2, and 8.4/10,000 person
      years in the second, third, and fourth quartiles, respectively (p < 0.001 for
      trend). After adjustment for age and other potential confounders, the odds ratios
      for PD in the lowest quartile was 5.2 (95% confidence interval, 1.5-25.6)
      compared with the top two quartiles. This relation was not evident beyond 4 years
      of follow-up. INTERPRETATION: Impaired olfaction can predate clinical PD in men
      by at least 4 years and may be a useful screening tool to detect those at high
      risk for development of PD in later life.

PMID- 18067175
TI  - Cannabinoids enhance susceptibility of immature brain to ethanol neurotoxicity.
AB  - OBJECTIVE: Marijuana and alcohol are most widely abused drugs among women of
      reproductive age. Neurocognitive deficits have been reported in children whose
      mothers used marijuana during pregnancy. Maternal consumption of ethanol is known
      to cause serious developmental deficits METHODS: Infant rats and mice received
      systemic injections of Delta(9)-tetrahydrocannabinol (THC; 1-10mg/kg) or the
      synthetic cannabinoid WIN 55,212-2 (1-10mg/kg), alone or in combination with
      subtoxic and toxic ethanol doses, and apoptotic neurodegeneration was studied in
      the brains RESULTS: Acute administration of THC (1-10mg/kg), the principal
      psychoactive cannabinoid of marijuana, markedly enhanced proapoptotic properties
      of ethanol in the neonatal rat brain. THC did not induce neurodegeneration when
      administered alone. Neuronal degeneration became disseminated and severe when THC
      was combined with a mildly intoxicating ethanol dose (3gm/kg), with the effect of
      this drug combination resembling the massive apoptotic death observed when
      administering ethanol alone at much higher doses. The detrimental effect of THC
      was mimicked by the synthetic cannabinoid WIN 55,212-2 (1-10mg/kg) and
      counteracted by the CB(1) receptor antagonist SR141716A (0.4mg/kg). THC enhanced
      the proapoptotic effect of the GABA(A) agonist phenobarbital and the N-methyl-D
      aspartate receptor antagonist dizocilpine. Interestingly, infant CB(1) receptor
      knock-out mice were less susceptible to the neurotoxic effect of ethanol.
      Furthermore, the CB(1) receptor antagonist SR141716A ameliorated neurotoxicity of
      ethanol INTERPRETATION: These observations indicate that CB(1) receptor
      activation modulates GABAergic and glutamatergic neurotransmission and primes the
      developing brain to suffer apoptotic neuronal death.

PMID- 18067177
TI  - How many deaths will it take? A death from asthma associated with work-related
      environmental tobacco smoke.
AB  - BACKGROUND: Despite epidemiologic, experimental and observational data on the
      association of environmental tobacco smoke (ETS) and adverse health effects, bar
      and restaurant workers remain exposed to ETS in the majority of states and
      countries. METHODS: Three public health surveillance systems were used to
      identify and conduct a follow-up investigation of a reported acute asthma death
      of a young waitress in a bar. RESULTS: The waitress collapsed at the bar where
      she worked and was declared dead shortly thereafter. Evaluation of the
      circumstances of her death and her medical history concluded that her death was
      from acute asthma due to environmental tobacco smoke at work. CONCLUSIONS: This
      is the first reported acute asthma death associated with work-related ETS. Recent
      studies of asthma among bar and restaurant workers before and after smoking bans
      support this association. This death dramatizes the need to enact legal
      protections for workers in the hospitality industry from secondhand smoke.

PMID- 18067178
TI  - Development and pilot test of hearing conservation training for construction
      workers.
AB  - BACKGROUND: Hearing conservation efforts in construction frequently rely on use
      of hearing protection devices (HPDs): however, training on HPDs is often not
      provided, and usage rates remain low. In this study, a hearing conservation
      training program was developed and pilot tested. METHODS: A theoretical model was
      selected as the basis for the program, and program contents and delivery methods
      were selected to optimize the effectiveness and flexibility of the training. Two
      evaluation measures were selected to assess training-related changes in self
      reported HPD use. The first was a validated method using concurrent work-shift
      noise dosimetry, and the second was a survey concerning workers beliefs and
      attitudes towards HPDs and HPD use. RESULTS: The training program was pilot
      tested on a single construction site. Complete assessment data were available for
      23 workers. The percent of time when hearing protection was used during noise
      levels above 85 dBA nearly doubled post-training, and the change was
      statistically significant. CONCLUSIONS: Pre- and post-training data from
      participating workers demonstrated that HPD use can be increased significantly
      with basic model-based training, even in industries with complex noise exposures
      such as construction.

PMID- 18067176
TI  - Shared occupational risks for transitional cell cancer of the bladder and renal
      pelvis among men and women in Sweden.
AB  - BACKGROUND: Unlike cancer of the bladder, cancer of the renal pelvis is not
      considered an occupational cancer and little is known about risks among women.
      METHODS: Using the Swedish national census and cancer registry-linked data (1971
      1989), we identified transitional cell cancers of the renal pelvis (N = 1,374)
      and bladder (N = 21,591). Correlation between cancer sites for the standardized
      incidence ratios (SIR) were determined using Pearson's coefficient of the log
      SIR. Relative risks of job exposure matrix variables were calculated using
      Poisson regression. RESULTS: Both cancer sites were significantly elevated among
      women and men employed in the machine/electronics industry, sedentary work, and
      indoor work, and men in the metal industry. The highest proportion of the bladder
      (12%) and renal pelvis (14%) cancers occurred among men employed in shop and
      construction metal work. Risks by industry were more correlated among women (r =
      0.49, P = 0.002) than men (r = 0.24, P = 0.04). Cancers of the renal pelvis were
      elevated in several occupational and industry groups for which there was no
      elevated bladder cancer risk. CONCLUSION: Cancers of the renal pelvis and bladder
      share common occupational risk factors that may be more frequent among women. In
      addition, there may be some jobs that pose an increased risk specifically for
      cancer of the renal pelvis but not bladder.

PMID- 18067179
TI  - A comparison of "Train-the-Trainer" and expert training modalities for hearing
      protection use in construction.
AB  - BACKGROUND: Few assessments have been conducted on the impact of a "Train-the
      Trainer" (T3) approach for training delivery. The present study compared the
      effectiveness of a noise induced hearing loss (NIHL) prevention training
      delivered using "Train-the-Trainer" and expert trainer modalities. METHODS:
      Participating construction companies were assigned to the Train-the-Trainer or
      expert trainer modalities. Workers were recruited from each company and then
      trained. The effectiveness of the modalities was assessed through the use of
      surveys. The accuracy of self-reported hearing protection device (HPD) use was
      also evaluated through on-site observation. RESULTS: Post-training scores for
      hearing conservation knowledge, perceived barriers, and current and intended
      future use of HPDs improved significantly for both training modalities. Subjects
      trained by T3 trainers significantly increased their beliefs regarding general
      susceptibility to NIHL, desire to prevent NIHL, and ability to recognize, and
      control hazardous noise exposures. The expert-trained groups significantly
      increased their beliefs regarding the benefits of HPD use and ability to ask for
      help with HPDs. The only changes that were significantly different between
      modalities were in general susceptibility to NIHL and effective use of HPDs.
      However, these beliefs differed significantly between subjects in the two
      modality groups prior to training. Self-reported HPD use was poorly correlated
      with observed use, calling into question the validity of survey-based HPD use
      measures in this context. CONCLUSIONS: The training improved beliefs regarding
      HPD use, increased workers' hearing conservation knowledge, and increased self
      reported HPD use. The effectiveness of the training was not found to be dependent
      on training modality.

PMID- 18067180
TI  - Failure of recognition of drug-induced parkinsonism in the elderly.
AB  - Our objective was to evaluate the ability of neurologists to recognize and
      diagnose drug-induced Parkinsonism (DIP) in the elderly. DIP is a diagnostic
      challenge because it can be indistinguishable from Parkinson's disease,
      especially in the elderly. It is frequently under-recognized by psychiatrists and
      primary care physicians. Atypical antipsychotics (AA) are advertised for their
      low propensity to cause DIP. This may add to problems with recognition. We
      performed a retrospective record review of consecutive new parkinsonian patients
      seen over 2 years in a movement disorders clinic to examine the frequency,
      causative agents, and diagnostic accuracy of DIP by physicians, particularly
      neurologists. Of 354 Parkinsonian patients evaluated, 24 (6.8%) had DIP, 46% of
      these were due to AA and 29% were caused by metoclopramide. Of the 24 patients
      with DIP, only one was previously diagnosed accurately according to records.
      Nineteen patients (79%) were previously evaluated by a neurologist, and none of
      them was diagnosed with DIP. The primary reason for failure to recognize DIP
      relates to under-recognition of AA as possible cause. A majority remained on the
      inciting agents while dopaminergic drugs were prescribed. DIP was reversible when
      the inciting drug was stopped. DIP is a common form of parkinsonism and is under
      recognized, even by neurologists. AA and metoclopramide do not appear to be well
      known to cause DIP. Cessation of the offending agent results in improvement of
      symptoms and would eliminate the need for dopaminergic agents, which are known to
      commonly cause side effects in the elderly.

PMID- 18067181
TI  - Eyelid opening apraxia in an AIDS patient.

PMID- 18067182
TI  - Aripiprazole: a treatment for severe coprolalia in "refractory" Gilles de la
      Tourette syndrome.
AB  - Coprolalia is one of the most distressing symptoms in Gilles de la Tourette
      syndrome. We report on a 28-year-old man with severe coprolalia at the forefront
      of symptoms, which had a dramatic impact on his social and professional life and
      that did not fluctuate for years. Moreover, he presented hypersensitivity to
      neuroleptics. The use of aripiprazole, as a last resort, induced a 75% of
      improvement of his symptoms with good tolerance. This suggests that aripiprazole
      constitutes a valuable therapeutic in coprolalia. Moreover, its biochemical class
      specificity makes it an alternative for patients hypersensitive to other classes
      of neuroleptics.

PMID- 18067184
TI  - Brain parenchyma sonography and 123I-FP-CIT SPECT in Parkinson's disease and
      essential tremor.
AB  - We aimed to investigate the accuracy of transcranial brain parenchyma sonography
      (TCS) for differentiation between idiopathic Parkinson's disease (PD) and
      essential tremor (ET) in comparison to (123)I-FP-CIT SPECT (FP-CIT SPECT).
      Seventy-four patients, in whom PD or ET was suspected on the basis of clinical
      criteria, were analyzed. The echogenicity of the substantia nigra (SN) and the
      striatal binding of dopamine transporters (DAT) were evaluated by TCS and FP-CIT
      SPECT, respectively. Three patients were excluded due to an insufficient
      transtemporal bone window using TCS. Forty-six and 25 patients were clinically
      classified as PD and ET. SPECT revealed a reduced DAT binding in 42 of all 71
      included patients. Thirty-six of the 42 patients with abnormal FP-CIT SPECT
      findings had a pathological SN hyperechogenicity, whereas TCS findings in the
      remaining 6 patients were normal. In 27 of 29 patients with normal SPECT findings
      the SN echogenicity was regular. Referring to FP-CIT SPECT, the sensitivity and
      specificity of TCS for detection of PD were 86 and 93%; the positive and negative
      predictive values were 95 and 82%, respectively. Sensitivity and specificity in
      detection of clinically diagnosed PD patients were 78 and 92% for TCS and 91 and
      100% for FP-CIT SPECT, respectively. In patients with pathological FP-CIT SPECT
      and pathological TCS, the extent of SN hyperechogenicity did not correlate with
      the degree of reduction in dopamine transporter binding on the side opposite of
      the more affected limb. TCS allows a reliable differentiation of PD and ET. The
      TCS SN hyperechogenicity does not correlate with the extent of dopaminergic
      neuron degeneration.

PMID- 18067183
TI  - Occupation and breast cancer risk among Shanghai women in a population-based
      cohort study.
AB  - INTRODUCTION: A total of 74,942 female subjects were recruited in a population
      based cohort study in Shanghai, China between 1997 and 2000. We examined the
      relationship between occupation and breast cancer risk. METHODS: Cases were 586
      women previously diagnosed with breast cancer at baseline and 438 women newly
      diagnosed with breast cancer during follow-up through December 2004. Eight
      controls were randomly selected for each case from cancer-free cohort members and
      frequency-matched to the cases by year of birth and age at diagnosis. Logistic
      regression was used to estimate odds ratios (ORs) and 95% confidence intervals
      (CIs) of breast cancer risk associated with occupations, adjusting for
      established breast cancer risk factors. RESULTS: In the prevalent breast cancer
      data analysis, increased risks of breast cancer were associated with technicians
      in engineering/agriculture/forestry (OR = 1.6, CI: 1.0-2.4), teaching personnel
      (OR = 1.5, CI:1.1-2.0), tailoring/sewing workers (OR = 1.6, CI:1.0-2.7), and
      examiners/measurers/testers (OR = 1.5, CI:1.1-2.1) among those who started the
      jobs at least 20 years ago. Among incident breast cancer cases, significantly
      increased risks were associated with medical/health care workers (OR = 1.4,
      CI:1.0-2.0), administrative clerical workers (OR = 1.5, CI:1.0-2.4),
      postal/telecommunication workers (OR = 2.2, CI:1.0-5.5), and odd-job workers (OR
      = 1.7, CI:1.1-2.8) among those who started the jobs at least 20 years ago. The
      excess risks were found in both prevalent and incident cases for
      postal/telecommunication workers and purchasing/marketing personnel, although ORs
      reached only marginal significance. CONCLUSIONS: This study suggests that white
      collar professionals and several production occupations may be associated with an
      increased risk of breast cancer.

PMID- 18067185
TI  - Investigation of an unusual, high-frequency jaw tremor with coherence analysis.
AB  - Normal physiological tremor of the jaw has a frequency of 6 to 8 Hz. A patient is
      described with jaw tremor at frequencies of 12 Hz during jaw movement and 15 Hz
      when the jaw was relaxed. The 15 Hz tremor was driven by synchronous, bilateral
      bursts of activity in the temporalis and masseter muscles, which alternated with
      digastric bursts. Coherence analysis indicated the tremor was highly correlated
      with both opening and closing muscle activity, and that the opening and closing
      muscles were about 180 degrees out of phase. The existence of two tremors with
      different, nonphysiological peak frequencies and the influence of attention,
      relaxation, and movement in switching from one tremor frequency to the other,
      suggest that more than one generator may be operating.

PMID- 18067186
TI  - Rasagiline improves freezing in a patient with primary progressive freezing gait.
AB  - We herein report the case of a 84-year-old man with a 4-year history of freezing
      of gait (FOG) consistent with the diagnosis of primary progressive freezing gait.
      Single photon emission tomography (SPECT) with a radiolabeled ligand of the
      dopamine transporter (DAT-SPECT) showed integrity of striatal dopaminergic
      terminals, whereas brain perfusion SPECT disclosed multiple areas of decreased
      perfusion in frontal and parietal lobes, as well as in the subcortical gray
      nuclei of both sides. Treatment with the new irreversible monoamine oxidase B
      inhibitor rasagiline at standard doses resulted in a rapid, dramatic, and
      sustained improvement of the frequency and duration of FOG episodes. In addition,
      brain perfusion SPECT after treatment showed a marked increase of the activity in
      all cortical areas as well as in the basal ganglia and thalamus. Rasagiline may
      prove to be an effective and safe treatment for this disabling condition.

PMID- 18067187
TI  - The relationship between impulsivity and impulse control disorders in Parkinson's
      disease.
AB  - A range of behaviors presumed to be related to dopaminergic medications have been
      recently recognized in Parkinson's disease (PD). We evaluated 50 consecutive
      cognitively intact PD patients on stable dopamine agonist and levodopa therapy
      and 100 healthy controls for compulsive sexual behavior, compulsive buying, or
      intermittent explosive disorders assessed by the Minnesota Impulsive Disorders
      Interview (MIDI), pathological gambling (South Oaks Gambling Screen, SOGS),
      impulsivity (Barratt Impulsiveness Scale), compulsivity (Maudsley obsessional
      compulsive inventory), and depression scores (Geriatric Depression Scale).
      Overall 28% PD (14/50) and 20% healthy controls (20/100) reported at least one
      abnormal behavior at MIDI or pathological SOGS score. PD patients had higher
      scores than controls for impulsivity (P = 0.006), compulsivity (P < 0.001), and
      depression (P < 0.001). There was no correlation between impulsivity,
      compulsivity, and depression scores in PD. Male gender and higher impulsivity
      score, but not dose and kind of dopaminergic medications, were associated in PD
      with increased probability of impulsive disorders at MIDI. Impulse control
      disorders are also common in the control population. Individual susceptibility
      factors, such as high impulsivity and depression, underline abnormal behaviors in
      PD patients treated with stable dopaminergic therapy.

PMID- 18067188
TI  - Multicenter study on deep brain stimulation in Parkinson's disease: an
      independent assessment of reported adverse events at 4 years.
AB  - Ongoing adverse events (AEs) at 4-years postsurgery in 69 patients with advanced
      Parkinson's disease (PD) who received deep brain stimulation (DBS) of the
      subthalamic nucleus (STN) (n = 49) or the internal globus pallidus (GPi) (n =
      20), in the framework of a subset of eight centers of a multicenter study, were
      analyzed by an independent ad hoc committee. At baseline, the patients' age, sex,
      disease duration, and clinical condition were virtually identical, as was the
      duration of follow-up. There were 64 AEs reported in 53% of STN DBS patients and
      eight AEs reported in 35% of GPi DBS patients. Most of the AEs were not deemed
      severe and were reported to be present "both with and without stimulation." The
      majority of the AEs affected patients' cognitive, psychiatric and behavioral
      status, as well as speech, gait, and balance, and most of these AEs occurred in
      STN DBS patients. When comparing patients who exhibited AEs with those who did
      not, it was found that in the STN DBS group, the patients with AEs had a longer
      disease duration, as well as more gait disorders and psychiatric disturbances at
      baseline.

PMID- 18067190
TI  - Cytobiocompatibility of collagen and ePTFE membranes on osteoblast-like cells in
      vitro.
AB  - In guided bone regeneration (GBR), a semipermeable membrane is placed over an
      osseous defect to create a secluded environment in which bone formation can
      proceed without ingrowth of connective tissue cells from the overlaying soft
      tissue. Although the cell-occlusive property of GBR membranes appear to be
      essential to new bone formation, the role of transmembrane tissue fluid diffusion
      is not known. The objective of this study was to evaluate the degree to which
      diffusion across commonly used GBR membranes can support functional properties of
      osteoblast-like cells in vitro. Cells from an established osteoblast-like line
      (SAOS-2) were cultured on membranes of cross-linked collagen, noncross linked
      collagen, and ePTFE. The membranes rested on metal grids which allowed the
      membranes to lightly contact the surface of the culture medium. As a control,
      cells were directly plated and cultured in control wells. At days 7 and 21, cells
      were harvested by scraping the membranes or culture wells and analyzed for
      expression of alkaline phosphatase (ALP), core binding factor 1 (cbfa-1), bone
      sialoprotein-2 (BSP-2), and osteocalcin (OC). Expression was determined by
      quantitative real-time PCR. Glucose-6-phosphate dehydrogenase (G6PD) served as a
      reference gene. The membranes were examined by transmission light microscopy. RT
      PCR revealed up-regulation of ALP of up to 60-fold and of cbfa-1 and BSP of up to
      threefold relative to G6PDH. Expression of OC was less then onefold. The
      expression profile for each of the four genes tested demonstrated small
      variations among cells grown on different membranes. Microscopic observations
      revealed remnants of undisrupted osteoblast-like cells attached to both collagen
      membranes. Cell morphology and spatial arrangement indicated that vitality was
      maintained. Diffusion through the three membranes evaluated in this study was
      sufficient to support osteoblast-like cell differentiation.

PMID- 18067189
TI  - Physicochemical characterization, in vitro, and in vivo evaluation of
      indomethacin-loaded nanocarriers self-assembled by amphiphilic polyphosphazene.
AB  - Copolymeric nanocarriers assembled by amphiphilic polyphosphazene bearing poly(N
      isopropylacrylamide) (PNIPAAm) and ethyl glycinate (EtGly) as substitutes, were
      investigated as drug vehicles for indomethacin (IND). The physicochemical
      characteristics of the novel nanocontainers were studied, including lower
      critical solution temperature (LCST), critical micelle concentration (CMC) and
      drug loading capacity. LCST measurements revealed that copolymer is more
      sensitive to the introduction of salts into aqueous solution compared with
      homopolymer. A significant decrease in CMC was observed when the temperature
      increased above LCST. As evidenced by transmission electron microscopy (TEM)
      measurement, morphological transformation from multicompartment into spherical
      nanoparticles was observed when nanocarriers with higher IND content were
      concerned. In vitro release tests suggested that IND-loaded nanocontainers
      exhibited pH dependent release profiles. In vivo pharmacokinetic study after
      subcutaneous administration provided a relatively sustained release behavior.
      Additionally, compared with free drug solution at the same dose, IND
      concentration in rat plasma showed a prolonged retention in experimental group
      treated with IND-loaded micelles. In vivo pharmacodynamic study based on both
      carrageenan-induced acute and complete Freund's adjuvant (CFA) induced adjuvant
      arthritis models indicated that sustained therapeutic efficacy could be achieved
      through intraarticular injection of IND-loaded micelles. Most importantly, local
      delivery of IND can avoid the severe gastrointestinal stimulation, which is
      frequently associated with oral administration.

PMID- 18067191
TI  - The influence of Sr doses on the in vitro biocompatibility and in vivo
      degradability of single-phase Sr-incorporated HAP cement.
AB  - In previous studies, we developed a new type of Sr-incorporated hydroxyapatite
      cement (Sr-HAC), which was shown to have many excellent physiochemical
      properties, by an ionic cement route (Guo et al., Biomaterials 2005;26:4073
      4083). As a further study, the main aims of this article were to examine the Sr
      HAC's in vitro biocompatibility, including acute toxicity, hemolytic reaction,
      pyrogen reaction, and cytoxicity, to evaluate its in vivo degradability during
      intramuscular and femur implantation, and also to investigate the influence of Sr
      doses on these properties. The in vitro results show that all of the Sr-HAC
      samples exhibit satisfactory biocompatibility, and the Sr/(Sr+Ca) molar ratio has
      an important effect on these properties. For example, the Sr-HAC with a
      Sr/(Sr+Ca) molar ratio of 5% (5% Sr-HAC) has higher biocompatibility than both
      the one with a Sr/(Sr+Ca) molar ratio of 10% (10% Sr-HAC) and the Sr-free one.
      The in vivo results of both the rabbit intramuscular and femur implantation
      experiments show that the Sr-HAC samples exhibit a much faster degradation rate
      than the Sr-free one, and that this also depends on the Sr/(Sr+Ca) molar ratio.
      Specifically, the mean degradation rate of the 10% Sr-HAC increases by an
      amplitude of 73.9 wt % compared with that of the Sr-free HAC. In addition, the
      optical transmission photographs show that the Sr doses play an important role on
      the interface between the implants and the new bone. The energy dispersion X-ray
      spectrum analysis indicates that there exists a gradient distribution of Sr
      element in the tight and bioactive interface between the implants and new bone,
      indicating that the Sr element takes a share in the mineralization of the new
      bone together with Ca element.

PMID- 18067192
TI  - Polyunsaturated fatty acid levels in the cerebrospinal fluid of patients with
      Parkinson's disease and multiple system atrophy.

PMID- 18067193
TI  - Freezing of gait and executive functions in patients with Parkinson's disease.
AB  - Freezing of gait (FOG) is a frequent, disabling symptom of Parkinson's disease
      (PD). FOG usually lasts a few seconds. It refers to brief paroxysmal events
      during which a subject is unable to start or continue locomotion. Despite its
      frequency, FOG pathophysiology is unclear. Because a frontal lobe dysfunction or
      a disconnection between the frontal lobe and basal ganglia has been implicated in
      FOG, we explored frontal functions in PD patients using neuropsychological tests.
      Thirteen early-stage PD patients [Hoehn & Yahr score (H&Y) < or = 2.5] with
      freezing during "on " state (FOG+), and 15 age-, H&Y score-, and disease-duration
      matched PD patients without freezing (FOG-) were investigated. No patient was
      demented or depressed. Assessment included the Unified Parkinson's Disease Rating
      Scale (UPDRS), FOG questionnaire, Mini Mental State Examination (MMSE), frontal
      assessment battery (FAB), phonemic verbal fluency, Stroop test (parts II and
      III), and ten-point clock test (TPCT). UPDRS and MMSE scores did not differ
      between the two groups. FAB, verbal fluency, and TPCT scores were significantly
      lower in FOG+ patients than in FOG- patients (FAB: P = 0.008; phonemic verbal
      fluency: P = 0.011; TPCT: P = 0.024). FOG correlated with lower scores at frontal
      tests in patients with early-stage PD.

PMID- 18067194
TI  - First Homo erectus from Turkey and implications for migrations into temperate
      Eurasia.
AB  - Remains of fossil hominins from temperate regions of the Old World are rare
      across both time and space, but such specimens are necessary for understanding
      basic issues in human evolution including linkages between their adaptations and
      early migration patterns. We report here the remarkable circumstances surrounding
      the discovery of the first fossil hominin calvaria from Turkey. The specimen was
      found in the Denizli province of western Turkey and recovered from within a solid
      block of travertine stone as it was being sawed into tile-sized slabs for the
      commercial natural stone building market. The new specimen fills an important
      geographical and temporal gap and displays several anatomical features that are
      shared with other Middle Pleistocene hominins from both Africa and Asia
      attributed to Homo erectus. It also preserves an unusual pathology on the
      endocranial surface of the frontal bone that is consistent with a diagnosis of
      Leptomeningitis tuberculosa (TB), and this evidence represents the most ancient
      example of this disease known for a fossil human. TB is exacerbated in dark
      skinned peoples living in northern latitudes by a vitamin D deficiency because of
      reduced levels of ultraviolet radiation (UVR). Evidence for TB in the new
      specimen supports the thesis that reduced UVR was one of the many climatic
      variables presenting an adaptive challenge to ancient hominins during their
      migration into the temperate regions of Europe and Asia.

PMID- 18067195
TI  - Inducing huntingtin inclusion formation in primary neuronal cell culture and in
      vivo by high-capacity adenoviral vectors expressing truncated and full-length
      huntingtin with polyglutamine expansion.
AB  - BACKGROUND: Huntington's disease (HD) is an inherited autosomal dominant
      neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat
      in exon 1 of the huntingtin (htt) gene. Vector-mediated delivery of N-terminal
      fragments of mutant htt has been used to study htt function in vitro and to
      establish HD models in rats. Due to the large size of the htt cDNA vector
      mediated delivery of full-length htt has not been achieved so far. METHODS: High
      capacity adenoviral (HC-Ad) vectors were generated expressing mutant and wild
      type versions of N-terminal truncated and full-length htt either in vitro in
      primary neuronal cells or in the striatum of mice. RESULTS: In vitro these
      vectors were used for transduction of primary neuronal cells isolated from E17
      mouse embryos. Expression of mutant htt resulted in the formation of htt
      inclusions, a surrogate marker of the HD pathology. Kinetics of generation and
      localization of htt inclusions differed between truncated and full-length htt
      carrying identical mutations. Following injection into the striatum vector
      mediated expression of mutant truncated htt led to prominent accumulation of htt
      inclusions in cell nuclei, while inclusions formed upon expression of mutant full
      length htt localized to the cytoplasm. CONCLUSIONS: These results indicate that
      HC-Ad vector-mediated in vitro and in vivo delivery of truncated and full-length
      mutant htt results in prominent inclusion formation in neuronal cells but in
      different cell compartments. These vectors will be useful tools for studying HD
      and may be used to generate large animal HD models.

PMID- 18067196
TI  - Gene delivery to the vasculature mediated by low-titre adeno-associated virus
      serotypes 1 and 5.
AB  - BACKGROUND: Vascular gene therapy requires safe and efficient gene transfer in
      vivo. Recombinant adeno-associated virus (AAV) is a promising viral vector but
      its use in the vasculature has produced conflicting results and serotypes other
      than AAV2 have not been intensively studied. We investigated the efficiency of
      alternative AAV serotypes for vascular gene delivery in vitro and in vivo.
      METHODS: Vascular cell lines were transduced in vitro with AAV vectors. Rabbit
      carotid arteries were transduced with AAV1, 2 and 5 encoding enhanced green
      fluorescent protein (eGFP) ( approximately 1.4 x 10(9) DNAse-resistant particles
      (drp)). Gene transfer in vivo was assessed at 14 and 28 days. High-titre doses of
      AAV2 encoding beta-galactosidase in vivo were also studied. RESULTS: In vitro,
      transgene expression was not observed in endothelial cells using AAV2 whereas the
      use of serotypes 1 and 5 resulted in detectable levels of transgene expression.
      Coronary artery smooth muscle cells (CASMCs) transduced with AAV2 demonstrated
      higher levels of GFP expression than AAV1 or 5. Transgene expression in vivo was
      noted using low-titre AAV1 and AAV5 ( approximately 1.4 x 10(9) drp) in the media
      and adventitia. Only delivery of AAV1eGFP resulted in neointimal formation (3/7
      vessels examined), with transgene expression noted in the neointima. Transgene
      expression with AAV2 was not detected in any layer of the blood vessel wall using
      low titre ( approximately 10(9) drp). However, high-titre ( approximately 10(11)
      drp) AAV2 resulted in transduction of cells in the media and adventitia but not
      the endothelium. CONCLUSIONS: AAV1 and AAV5 have advantages over AAV2 for
      vascular gene delivery at low titres.

PMID- 18067197
TI  - Knowledge of results and learning to tell the time in an adult male with an
      intellectual disability: a single-subject research design.
AB  - The present study investigated whether knowledge of results, in the form of
      visual and audible feedback, would increase the accuracy of time-telling in an
      individual with an intellectual disability. A 19-year-old male with mild
      intellectual disability participated in this A1-B1-A2-B2 single-subject study
      design. The task involved correctly identifying the time given on a computer.
      Data, based on the Wilcoxon signed-rank test, showed that the participant
      demonstrated a greater number of correct responses during the intervention
      phases. Incorporating knowledge of results into a learning strategy for this
      individual with intellectual disability resulted in an increased ability to
      accurately identify the correct time on an analogue clock. There is a need to
      replicate the study design to increase the external validity and generalization
      of results. The strategies described in the present study may also be useful for
      occupational therapists who teach individuals with intellectual disability to
      gain skills in their everyday activities of daily living (ADLs).

PMID- 18067198
TI  - The significance of dyslexia screening for the assessment of dementia in older
      people.
AB  - Dyslexia and Dementia are disorders that share cognitive impairments in
      attention, language, and working memory. It is therefore possible that the
      presence of dyslexia may influence the assessment of the severity of dementia and
      potentially lead to the development of atypical forms of dementia. The present
      study investigated the prevalence of problems suggestive of dyslexia with a brief
      self-report questionnaire in a sample of 195 older adults referred to a Memory
      Clinic for dementia assessment. Ten percent reported problems suggestive of
      dyslexia consistent with the estimated prevalence in the general population. This
      group performed significantly lower in a number of attention and language related
      tests but not in other cognitive domains. These results highlight the importance
      of dyslexia screening for the assessment of dementia, not least because the
      choice of treatment is guided by the outcome of the assessment of the severity
      and the type of dementia.

PMID- 18067199
TI  - Formation and physicochemical features of hybrid threadlike micelles in aqueous
      solution.
AB  - We investigate the construction of long, stable hybrid threadlike micelles
      consisting of polyelectrolytes and oppositely charged surfactants in aqueous
      solution and examine the physicochemical features such as their structure and
      viscoelastic behavior in aqueous solution. The most important point for their
      construction is the careful control of interactions, especially electrostatic
      interactions, caused between the surfactants and polyelectrolytes. Incorporated
      polyelectrolytes are fully extended in these hybrid threadlike micelles
      irrespective of the molecular weight of the polymer. The viscoelastic behavior of
      the hybrid threadlike micellar solution is similar to that of ordinary threadlike
      micellar systems consisting of low-molecular-weight substances. However, the
      inclusion of polymers in the micelles causes differences in their mechanical
      properties.

PMID- 18067200
TI  - Effect of the magnetic field on the supramolecular structure of chiral smectic C
      phases: (2)H NMR studies.
AB  - We present a theoretical and experimental (2)H NMR study of the effect of
      external magnetic fields on the supramolecular organization of chiral smectic
      liquid-crystalline mesophases, such as SmC* and re-entrant SmC*. Three
      experimental cases in which the supramolecular helical structure of the smectic
      C* phase is unwound by a magnetic field (H), parallel to the helical axes of this
      phase, are discussed in detail. Unwinding of the helical structure is described
      by using a theoretical model based on the Landau-de Gennes theory, which allows
      us to explain the transition temperatures among the SmA, SmC*, and uSmC* phases.
      The energy-density behavior in the vicinity of the transitions and the value of
      the critical magnetic field H(C) for unwinding the helical structure are
      discussed by applying this model to three ferroelectric smectogens (MBHB,
      11EB1M7, ZLL7/*), which are studied by (2)H NMR spectroscopy at different
      magnetic fields (from 2.4 to 9.4 Tesla). Furthermore, the tilt angle of the three
      smectogens in the SmC* phase has been directly evaluated, for the first time, by
      comparing the quadrupolar splittings at different magnetic fields. In one case,
      (2)H NMR angular measurements are used to obtain the tilt angle in the re-entrant
      smectic C phase.

PMID- 18067201
TI  - New concepts in the therapeutic options of liver metastases from colorectal
      cancer.
AB  - Colorectal cancer is one of the most frequent malignant neoplasms causing
      approximately 10% of cancer deaths. Up to 30% of patients with primary colorectal
      cancer have already liver metastatic disease at the time of diagnosis. Untreated
      patients with liver metastases share a poor prognosis with an average survival of
      12 months. In contrast, patients whose metastatic lesions are surgically treated
      have an average 5-year survival rate of 40%. Only 10-15% of initial colorectal
      liver metastases are considered as being resectable. In the remaining patients,
      the current trend is to downstage initially unresectable metastases by
      neoadjuvant therapy (systemic or regional chemotherapy, portal vein embolization 
      PVE - or hepatic artery chemoembolization), tumor ablation and two-stage
      hepatectomy, alone or in combinations. This study reviews the current therapeutic
      options for colorectal liver metastases and their contribution to improve
      survival rates.

PMID- 18067202
TI  - Surgery after induction chemoradiotherapy for non small cell lung cancer: when
      and why.
AB  - Stages I and II non small cell lung cancer (NSCLC) are primarily treated by
      anatomic pulmonary resection. Selected patients with stage IIIB disease are still
      candidates for surgical treatment. Unfortunately most patients with locally
      advanced NSCLC don't benefit by surgery alone or even by the combination of
      chemotherapy and radiotherapy. In order to achieve local and distant disease
      control, which seems to be the cause of failure of the above mentioned
      treatments, surgery after induction chemoradiotherapy has been proposed. This
      approach seems to be the state of the art of therapy for these patients improving
      survival but with eventual increased risks, especially pulmonary and septic
      complications. This review of previously published studies indicates the
      important role of this combined treatment in terms of survival and its risks
      related either to induction treatment or to surgery.

PMID- 18067203
TI  - Radiation dermatitis: implicated factors, clinical aspects, possible prevention,
      and medical care.
AB  - The increasing incidence of cancer is due to many factors. Among them quite
      significant is considered the rising proportion of older people in the population
      and the modern methods of early diagnosis. Radiotherapy (RT), along with surgery
      and chemotherapy, is a major therapeutic modality in the management of cancer. In
      the context of current treatment methods and practice, approximately half of the
      patients with cancer will receive RT at some stage of their illness. RT can lead
      to cure some kinds of cancer but it can also be delivered for palliation.
      Unfortunately, skin damage is a complication affecting by and large all patients
      receiving external beam RT. In order to minimize the risk of this damage it would
      be helpful to know the complex underlying molecular mechanisms and evaluate the
      related clinical symptoms, not only for medical but also for psychological
      reasons related to the patient. The purpose of this article was to review the
      current approaches to this particular clinical condition, in order to realize an
      effective patient-oriented clinical practice and keep this radiation-induced
      complication as low as possible.

PMID- 18067204
TI  - Outcome of metastatic non-small cell lung carcinoma patients receiving
      docetaxelcisplatin combination chemotherapy: single institution experience.
AB  - PURPOSE: Despite advances in the detection and treatment, the long-term survival
      of patients with advanced nonsmall cell lung cancer (NSCLC) remains poor, with a
      5-year overall survival (OS) of less than 5%. We conducted this observational
      study to determine the influence of docetaxel plus cisplatin combination
      chemotherapy on response, time to progression (TTP) and OS, and to evaluate its
      tolerability in chemotherapy-naive patients with metastatic NSCLC. PATIENTS AND
      METHODS: Patients with histologically or cytologically confirmed stage IV NSCLC
      who met the following criteria were eligible for the study: no previous
      chemotherapy, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0
      2, objectively measurable disease, adequate bone marrow reserve, normal hepatic
      and renal function. Patients received docetaxel 75 mg/m(2) and cisplatin 75
      mg/m(2), both given on day 1. Cycles were repeated every 3 weeks and a total of 4
      6 cycles were scheduled to be administered. RESULTS: 50 consecutive eligible
      patients were enrolled into the study. Median follow-up time was 6 months (range
      1-21). Median age was 61.5 years (range 39-75). Forty-eight (96%) patients were
      male. Histological type was squamous cell carcinoma in 21 (42%) patients,
      adenocarcinoma in 11 (22%) and undifferentiated carcinoma in 18 (36%). The median
      OS time was 16 months (range 7.1-24.9; 95% CI: 8-24). One-year OS was 56.3%.
      Overall response rate was 44% with 40% partial (PR) and 4% complete responses
      (CR). Twenty-eight percent of patients had stable disease (SD) and 28%
      progressive disease (PD). The median TTP was 4 months (range 2-13; 95% CI: 2.4
      5.5). CONCLUSION: Docetaxel/cisplatin combination demonstrated efficacy
      comparable to other platinum-containing doublets.

PMID- 18067205
TI  - Palifermin for prevention of oral mucositis after haematopoietic stem cell
      transplantation- single centre experience.
AB  - PURPOSE: Oral mucositis (OM) is one of the most debilitating and common side
      effects in patients treated with high-dose chemotherapy supported by
      haematopoietic stem cell transplantation (HSCT). We tested the effectiveness of
      palifermin to avoid oral mucosal injury induced by the conditioning regimen.
      PATIENTS AND METHODS: Twenty patients with haematological malignancies were
      treated with palifermin for prevention of OM during HSCT procedures. Nine
      patients received allogeneic haematopoietic stem cells, and in 11 autologous HSCT
      was performed. The control group was composed of patients who had been treated
      with HSCT previously, before the palifermin era. The source of graft was
      peripheral blood. RESULTS: Among patients treated with palifermin no grade 2-4 OM
      was observed. No patient had to receive opioid analgesics or total parenteral
      nutrition. 30% of the patients developed grade 1 OM of 4-5 days' duration. In the
      control group OM was observed in all cases, with 50% of the patients developing
      grade 3-4 OM. Median duration of OM was 10 and 12 days for auto- and allogeneic
      patients, respectively. In comparison with the control group, treatment with
      palifermin was associated with significant reduction of grade 2-4 OM, shorter
      duration of OM, less analgesics intake, and reduced number of days with
      antibiotic treatment. Additionally, allogeneic patients treated with palifermin
      had shorter time to platelet engraftment. CONCLUSION: Palifermin reduces
      incidence, severity and duration of OM, and decreases the number of days with
      analgesics and antibiotics. For allogeneic patients it can shorten the time to
      platelet engraftment, but this observation needs further studies.

PMID- 18067206
TI  - Peculiarities of menstrual function in mothers of children with acute
      lymphoblastic leukemia.
AB  - PURPOSE: To analyse the peculiarities of menstrual function in a group of mothers
      having children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS:
      The case-control method was used, taking into consideration the age at first
      menstruation, cycle regularity, duration of menstruation and discharge quantity.
      The case group included 160 mothers with children suffering from ALL and the
      control group included 160 mothers having healthy children of the same age and
      sex. RESULTS: Alterations of the menstrual function in mothers of patients with
      ALL occur with statistically higher rate as compared with mothers having healthy
      children. Mothers of pediatric patients with ALL showed later menarche (>or= 15
      years of age), reduced (to 2 days) or prolonged (over 6 days) menses duration, as
      well as irregularity of the menstrual cycle combined with prolonged menses
      duration. CONCLUSION: Menstrual disorders in mothers of child ren with ALL occur
      with reliably higher frequency as compared with women having healthy children. A
      common origin of both events (predisposition to malignancies and menstrual
      disorders) is suggested pointing to inherited genomic instability.

PMID- 18067207
TI  - Increased levels of tumor markers in the follow-up of 400 patients with breast
      cancer without recurrence or metastasis: interpretation of false-positive
      results.
AB  - PURPOSE: To analyze, study and interpret the increased levels of tumor markers in
      breast cancer patients without recurrence or metastasis. PATIENTS AND METHODS: We
      studied a series of 400 patients with stage 1 breast cancer during a 3-year
      follow-up after primary treatment. Follow-up included frequent serum estimation
      of CEA, CA 15.3, CA 125, CA 27-29, TPA and TPS tumor markers. RESULTS: Of 358
      patients being continuously disease-free, 18 (5%) cases showed false-positive
      levels of tumor markers, associated with benign conditions and not to cancer
      recurrence or metastasis. These conditions included ovarian cysts, thyroid
      disorders, hepatitis, renal stone and sarcoidosis. CONCLUSION: The value of
      increased tumor markers should be interpreted cautiously because it doesn't
      always imply disease recurrence. Tumor markers may increase in many benign
      conditions.

PMID- 18067208
TI  - Current diagnostic approaches in tumor-induced bone disease.
AB  - PURPOSE: To assess the role of the current imaging methods in the diagnosis,
      staging and post-therapeutic monitoring of cancer-induced bone disease. PATIENTS
      AND METHODS: 183 cancer patients underwent baseline whole body bone scintigraphy
      (WBBS) with 555- 740 MBq (99m)Tc-MDP. Computed tomography (CT) was carried out in
      43 patients, and magnetic resonance imaging (MRI) in 26 patients with abnormal
      uptake on the bone scan in order to differentiate metastatic or degenerative
      skeletal lesions with similar scintigraphic appearance. Sixty-four patients with
      established tumor-induced bone disease were followed-up after their anticancer
      treatment. RESULTS: WBBS was positive for metastatic disease in 54 patients and
      normal skeletal scan was obtained in 28 patients. Comparative analysis of the
      sensitivity and specificity of WBBS in relation to CT for diagnosis of metastatic
      spots in the examined group of 43 patients showed: for WBBS 93.3% (28/30) and
      92.8% (13/14), respectively; for CT 90% (27/30) and 100% (13/13), respectively.
      Sensitivity and specificity of WBBS in relation to MRI in the examined group of
      26 patients showed: for WBBS 86.6% (13/15) and 77.7% (7/9), respectively/ for MRI
      100% (15/15) and 88% (8/9), respectively. Scintigraphic follow-up examinations of
      64 patients after appropriate therapy showed partial response (PR) in 28 cases,
      stable disease (SD) in 12, progressive disease (PD) in 10, pathological fractures
      in 11 and "flare phenomenon) in 3 cases. CONCLUSION: In most cases WBBS is suffi
      cient to find and locate osseous metastases. Because of the lower specificity of
      WBBS, patients with spots of increased mineral metabolism of unclear character
      and persisting pain in the spine necessitate target CT or MRI to evaluate the
      characteristics of the detected scintigraphic changes.

PMID- 18067209
TI  - Association between bone scintigraphy and serum levels of tumor markers in the
      detection of bone disease in breast cancer patients.
AB  - PURPOSE: To evaluate the diagnostic value of bone scan in association with
      measurements of serum CEA, CA 15-3 and TPA levels in breast cancer (BC) patients.
      PATIENTS AND METHODS: From September 1999 to January 2005, 89 women with BC who
      had undergone bone scintigraphy as part of their follow-up were retrospectively
      evaluated. Serum tumor markers levels were compared with the results of bone
      scintigraphy. Patients with positive bone scans were divided into 3 groups: group
      1: 1-3, group 2: 4-5, group 3: >5 bone lesions. Serum CEA, CA 15-3 and TPA levels
      of 7 ng/ml, 35 U/ml and 90 U/I, respectively, were adopted as the upper limit of
      normal. RESULTS: Serum CA 15-3 was significantly higher in patients with a
      positive bone scan (p=0.017). For CEA and TPA, no significant difference was
      found between patients with and without bone metastases. Twenty-five of 70
      patients (36%) with normal CEA had bone metastases. Four of 50 (8%) patients with
      normal CA 15-3 and 15 of 51 (29%) patients with normal TPA had a positive bone
      scan. The combination of CA 15-3 with TPA showed 100% sensitivity in detecting
      bone metastases in all patient subgroups. In all 42 patients without bone
      metastases, CA 15-3 and/or TPA levels were normal. CONCLUSION: CA 15-3 but not
      CEA or TPA is sensitive and specific for the correct determination of bone
      scintigraphy. CA 15-3 plus TPA represent the best combination in association with
      bone scanning. However, due to frequent false negative results of all tumor
      markers, it is not recommended to reject a bone scan on the basis of tumor
      markers levels.

PMID- 18067210
TI  - Evaluation of combined h-TERT, bcl-2, and caspases 3 and 8 expression in
      cutaneous malignant melanoma based on tissue microarrays and computerized image
      analysis.
AB  - PURPOSE: Deregulation of apoptotic pathways in cutaneous malignant melanoma
      appears to be correlated with chemoresistance and poor prognosis. Furthermore,
      telomerase (especially h-TERT) expression induces proliferation and also
      represents a potential target for vaccination regarding some types of
      malignancies. MATERIALS AND METHODS: Using tissue microarrays (TMA) technology,
      25 paraffin-embedded tissue samples of histologically confirmed malignant
      melanomas were cored at a diameter of 2 mm and re-embedded into one recipient
      block (final TMA density 24/25-96%). Immunohistochemistry (IHC) was performed by
      the use of anti-bcl-2, anti-caspase 3, anti-caspase 8 and anti- h-TERT
      antibodies. Protein expression levels were evaluated using a computerized image
      analysis system (CIA). SPSS (chi square test and inter-rater kappa) was used for
      statistical analysis. RESULTS: Strong protein expression was observed in 1/24
      (4.1%), 1/24 (4.1%), 2/24 (8.2%), and 4/24 (16.4%) cases regarding h-TERT,
      caspase 3, caspase 8 and bcl-2, respectively. Moderate was observed in 7/24
      (29.1%), 8/24 (32.2%), 5/24 (20.2%), and 8/24(32.2%) cases, whereas reduced or
      absent expression demonstrated 16/24 (65%), 15/24 (60.2%), 17/24 (68.5%), and
      12/24 (50 %) cases. Statistical significance was assessed correlating age to
      caspase 3 (p=0.05), Breslow's thickness to telomerase (p=0.013) and to bcl-2
      (p=0.053), Clark's level to telomerase (p=0.008) and to bcl-2 (p=0.022), and
      finally ulceration to telomerase expression (p=0.007). CONCLUSION: bcl-2 and
      telomerase expression are correlated to critical parameters of malignant
      melanoma, affecting its biological behavior. Furthermore, downregulation of
      proteins such as caspases 3/8, which normally induce apoptosis, is perhaps
      associated with resistance of the applied chemotherapeutic strategies in this
      type of malignancy.

PMID- 18067211
TI  - The influence of three newly synthesized pyrimidine-containing compounds on
      micronucleus induction and tumor growth.
AB  - PURPOSE: To study the micronucleus (MN)-inducing (both in vivo and in vitro) and
      antitumor activity in vivo of 3 newly synthesized compounds (DGS-658, DGB-664A
      and DGS-666), and the influence of these compounds on MN-inducing and antitumor
      activity of cyclophosphamide (CP). MATERIALS AND METHODS: The compounds were
      tested for their toxicity and MN-inducing activities in HeLa tumor cell line and
      Swiss mice. Antitumor activity was studied on mouse Ehrlich ascites carcinoma
      (EAC) by means of evaluation of tumor (ascites) volume and mean lifespan (MLS).
      To study the influence of the compounds on MN-inducing effect of CP (30 mg/kg),
      one hour after i.p. injection, mice were treated with the compounds at doses
      equal to (1/2) of LD(50) (lethal dose). To study the effect of possible
      enhancement of antitumor activity, the compounds were injected one hour after CP
      (at doses equal to maximum tolerated dose / MTD), for 6 consecutive days. One day
      after the last injection half of the mice with EAC were sacrificed and antitumor
      activity was assessed by means of ascites volume inhibition. Also the frequency
      of MN and the number of viable cells (by means of trypan blue exclusion) was
      evaluated in ascites. The rest of the mice were kept until death and then the MLS
      was calculated. RESULTS: Only DGS-666 induced significant increase in the number
      of MN and prolonged the MLS of mice with EAC. Combined action of DGS-658, DGS
      664A, DGS-666 and CP showed a significant increase in the number of EAC cells
      with MN by 17.5%, 23.1% and 50.2%, respectively, compared with CP action (p
      <0.001). Antitumor effect of combined action of the compounds with CP (based on
      the ascites volume) was increased compared with CP effect by 17.7% (p >0.05; DGS
      658 and DGS-664A) and 28.2% (p <0.001; DGS- 666). Combined action of CP and the
      DGS-658, DGS-664A, DGS-666 prolonged significantly the MLS of mice compared with
      CP action by 51.2%, 56.0% and 110.4%, respectively (p <0.001). CONCLUSION: These
      newly synthesized compounds, practically inactive in MN induction and possessing
      no or slight antitumor activity, increased significantly the mutagenic and
      antitumor activity of CP, one of the most frequently used chemotherapeutic agents
      in clinical oncology. The compounds are practically non-toxic making them very
      attractive for further studies.

PMID- 18067213
TI  - Reevaluating pancreatic duct ligation in Whipple procedure.
AB  - In an effort to avoid the morbidity and mortality related to pancreaticojejunal
      anastomosis after pancreaticoduodenectomy (PPD), we report on the treatment of
      the pancreatic stump by pancreatic duct ligation (PDL) following Whipple
      procedure. We studied a series of 9 consecutive unselected patients (8 with
      pancreatic cancer and 1 with chronic pancreatitis). Of those, pancreatic fistula
      occurred in 4 patients and persisted for 14 to 58 days (mean 35.4 days). Two
      patients died within 30 days after surgery from causes not related to PDL. None
      of our patients developed diabetes mellitus following PDL surgery, nor any of the
      other frequently mentioned postoperative complications such as acute pancreatitis
      or pancreatic insufficiency. In conclusion, PDL may occasionally lead to a
      controlled pancreaticocutaneous fistula with fading inactive contents over time
      not causing further metabolic complications but is a safe, simple and fast
      alternative to pancreaticojejunostomy.

PMID- 18067212
TI  - Microprocessor-controlled iontophoretic drug delivery of 5-fluorouracil:
      pharmacodynamic and pharmacokinetic study.
AB  - PURPOSE: The purpose of this study was to fabricate monolithic 5-fluorouracil (5
      FU) transdermal patch with microprocessor- controlled iontophoretic delivery, to
      evaluate the pharmacodynamic effects on Dalton's lymphoma ascites (DLA) induced
      in Balb/c mice, and to study pharmacokinetics in rabbits. MATERIALS AND METHODS:
      The transdermal patches were prepared by solvent casting method; a reprogrammable
      microprocessor was developed and connected to the patches. DLA cells were
      injected to the hind limb of Balb/c mice (10 animals/group). In the first group
      of mice 5-FU was administered i.v. (12 mg/kg). In the second group of mice,
      transdermal patches (20 mg/patch/animal) were installed and kept for 10
      consecutive days, while the third (control) group was kept without any treatment.
      The tumor diameter was measured every 5th day for 30 days, and the animal
      survival time and death pattern were studied. The electric current density
      protocol of 0.5 mA/cm(2) for 30 min was used in the pharmacokinetic study in
      rabbits. RESULTS: There was a significant reduction in tumor volume in the
      animals treated with monolithic matrix 5-FU transdermal patch compared to
      untreated controls and i.v. therapy. Tumor volume of the control animals was 5.8
      cm(3) on the 30th day, while in 5-FU with transdermal patch delivery animals it
      was only 0.23 cm(3) (p <0.05). DLA cells tumor-bearing mice treated with 5-FU
      with transdermal patch had significantly increased lifespan (ILS). Control
      animals survived only 21+/-1 days after the tumor inoculation, while i.v. 5-FU
      and 5-FU patches animals survived 24+/-2.7 days and 39.5+/-1.87 days with ILS of
      25.58% and 88.09%, respectively (p <0.01). There was significant sustained
      release of 5-FU through microprocessor-controlled patches and half-life was
      significantly higher (p <0.05) compared to the i.v. route. CONCLUSION: Cytotoxic
      concentration of 5-FU can be achieved through the transdermal drug delivery and
      effective therapeutic drug concentration can be maintained up to 24 h, with less
      toxicity. A new generation of transdermal drug delivery systems based on
      microprocessor-controlled iontophoresis is in the late stages of development and
      promises to enhance the treatment of local and systemic medical conditions. The
      incorporation of microprocessor into these systems has been an important
      advancement to ensure safe and efficient administration of a wide variety of
      drugs.

PMID- 18067214
TI  - Malignant histiocytosis with central nervous system involvement and hepatic
      mucinous cystadenoma in a single patient with review of the literature.
AB  - Malignant histiocytosis is a rare neoplasm of the reticuloendothelial system
      characterized by neoplastic proliferation of tissue histiocytes. We report a case
      of malignant histiocytosis in a 64-year-old female initially operated on for a
      mucinous cystadenoma of her liver. Four months after the operation, skin
      induration on the neck and anterior thoracic wall and systemic lymphadenopathy
      were noted. Histology and immunohistochemistry of the lymph node and bone marrow
      specimens showed extensive infiltration with atypical cells, resembling malignant
      histiocytes (CD45, CD45RO, CD11c, CD68, lysozyme, antitrypsin and alpha1
      antichymotrypsin positive; CD1, CD35, B-cell and T-cells markers negative). She
      was treated with vinblastine, methotrexate and dexamethasone (3 cycles) without
      response. The therapy was switched to CHOP (cyclophosphamide, vincristine,
      doxorubicin, and prednisone) with disappearance of lymphadenopathy. Bone marrow
      infiltration by histiocytes was reduced to 20%. Two months after completion of 8
      cycles of CHOP she experienced severe headaches, vomiting, loss of consciousness,
      and developed paraparesis. A CT scan of the brain was normal but the
      cerebrospinal fluid cytology showed presence of histiocytes. The patient was then
      treated with intrathecal methotrexate, prednisolone and cytosine-arabinoside and
      systemic chemotherapy with etoposide and cyclophosphamide. Her condition
      improved, she became conscious, her headache diminished, she became mobile but
      skin and nodal lesions reappeared along with extensive marrow histiocytic
      infiltration. She finally died 22 months after diagnosis.

PMID- 18067215
TI  - Primary pulmonary melanoma diagnosis: the role of immunohistochemistry and
      immunocytochemistry.
AB  - We report a rare case of a primary melanoma of the lung initially presenting with
      haemoptysis, which was diagnosed using 2 new immunohistochemistry markers and
      cytology with immunocytochemistry. A 67-year-old male underwent repeated major
      lung resections and died because of early recurrences of a primary pulmonary
      melanoma as detailed study excluded other primary foci. The diagnosis of the
      patient's last recurrence was achieved on a fine needle aspiration (FNA) specimen
      with immunocytochemistry. To the best of our knowledge this is the first case of
      primary pulmonary melanoma diagnosed by immunocytochemistry on FNA material.

PMID- 18067216
TI  - Urachal mucinous adenocarcinoma: a case report.
AB  - Adenocarcinomas account for 0.5-2% of all bladder cancers. Urachal carcinoma is a
      rare neoplasm which represents 0.01% of all cancers in adults and account for one
      third of bladder adenocarcinomas. A 65-year-old white man with an urachal
      mucinous adenocarcinoma is reported. None of the known predisposing risk factors
      for bladder cancer -such as tobacco use and professional exposure to chemicals 
      were identified in his past medical history. The patient suffered from multiple
      sclerosis for almost 11 years and in the last 6 years he was treated with low
      doses of mitoxantrone. He underwent a partial cystectomy and en block excision of
      the umbilical ligament and remains disease-free after one year. The development
      of this rare neoplasm should not be clearly dissociated from multiple sclerosis,
      either aetiologically sharing an unidentified common causative factor or due to
      its treatment with mitoxantrone.

PMID- 18067217
TI  - Subcutaneous metastasis from a gastrointestinal stromal tumor of the stomach: a
      case report.
AB  - Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the
      stomach, which account for approximately 3.6% of all gastric tumors. They may or
      may not be malignant. Malignant GIST rarely metastasizes to distant organs. We
      report a case of a gastric GIST diagnosed in a 69- year-old woman presented with
      a synchronous subcutaneous paraumbilical metastasis. Computed tomography (CT)
      scan demonstrated a space-occupying lesion arising from the gastric wall with a
      second well-circumscribed lesion in the subcutaneous tissue which infiltrated the
      aponeurosis of the right rectus abdominis. The patient underwent total
      gastrectomy and resection of the subcutaneous mass. Pathologic examination of the
      gastric tumor and subcutaneous mass showed histological and immunohistochemical
      characteristics of a GIST. The patient succumbed on the 4th postoperative day.
      Gastric stromal tumor metastasis must be taken into consideration in the
      differential diagnosis of a palpable paraumbilical mass in a patient diagnosed
      with malignant GIST.

PMID- 18067218
TI  - Why individualize breast cancer survivors' follow-up?

PMID- 18067219
TI  - The use of a Marlex mesh with methylmethacrylate to repair large full-thickness
      defects after subtotal sternectomy caused by chondroma.

PMID- 18067220
TI  - Sudden death: a case report of hepatocellular carcinoma with tumor thrombus
      extending into the right atrium.

PMID- 18067221
TI  - Paul Broca (1824-1880): founder of anthropology, pioneer of neurology and
      oncology.
AB  - Paul Broca was an eminent surgeon, neurologist and anthropologist. He wrote many
      articles on brain anatomy, pathology of bones and joints, aneurysms, craniometry
      and physical anthropology, and he invented measuring instruments which are used
      even today. He described the condition of aphasia, called Broca's aphasia. Over a
      dozen anatomical features, including parts of the brain governing speech and
      smell, have made his name familiar to students. Thanks to his works on cancer and
      on tumors in general, he is considered as precursor of oncology.

PMID- 18067222
TI  - [Enhancing practical research of high-throughput diagnostic techniques in field
      of epidemiology].

PMID- 18067223
TI  - [A high-throughput diagnostic method for detecting pathogenic microbes].
AB  - OBJECTIVE: To develop a high-throughput diagnostic method with suspension array
      technique for detecting pathogenic microbes. METHODS: The probes and positive
      controls of 56 kinds of pathogenic microbes were designed, synthesized, and used
      to detect pathogenic microbes with suspension array technique. RESULTS:
      Fluorescence signals of 56 positive controls were higher than those of the
      negative controls, and there was no cross-reaction between the probes and
      positive controls of different microbes. CONCLUSION: Based on suspension array
      technique, the high-throughput diagnostic method may be useful in clinical
      detection of pathogenic microbes.

PMID- 18067224
TI  - [Identification of closely related bacteria via phylogenetic methods].
AB  - OBJECTIVE: To differentiate closely related pathogenic bacteria via phylogenetic
      method on the basis of gyrB gene sequences. METHODS: GyrB sequences of 19 strains
      of E.coli, 13 Shigella spp. 2 Aeromonas caviae, 2 Aeromonas hydrophilia,1
      Aeromonas veronii were determined and combined with sequences retrieved from
      public databases to construct phylogenetic trees. For each sequence tested, the
      identification deduced from the clustering relation of sequences was compared
      with the phenetic identification. RESULTS: All the tested sequences, except those
      of Shigella boydii and Shigella dysenteriae, were corresponded with the 5 closest
      sequences on the tree at the species level. While the BLAST queries returned some
      other bacteria organisms or undetermined entries. CONCLUSION: Phylogenetics
      displays good discriminative power in bacterial sequences differentiation.

PMID- 18067225
TI  - [Establishment of fingerprint database for drug-resistant strain of Acinetobacter
      baumannii by AFLP method].
AB  - OBJECTIVE: To establish fingerprint database of drug-resistant strain of
      Acinetobacter baumannii with AFLP genotype. METHODS: Twenty-seven strains of A.
      baumannii were clinically isolated. The microbial sensitivity to 13 antibiotics
      was analyzed according to NCCLS 2004. The genotype was analyzed by amplified
      fragment length polymorphism (AFLP) method. RESULTS: The results were consistent
      with those with AFLP database. CONCLUSION: The database of AFLP fingerprint may
      have practical value for identification of drug-resistant Acinetobacter
      baumannii.

PMID- 18067226
TI  - [Astragalus polysaccharides and astragalosides regulate cytokine secretion in LX
      2 cell line].
AB  - OBJECTIVE: To investigate the anti-fibrosis mechanism of radix astragali through
      the observation on regulating cytokine secretion by astragalosides and astragalus
      polysaccharides in hepatic stellate cell line LX-2. METHODS: Astragalus
      polysaccharides and astragalosides at concentration of 25 microg/ml and 300
      microg/ml were added to LX-2 cell culture.After 24 h culture total RNA contents
      were extracted and TGF-beta1, HGF, MP2 and MMP9 mRNA were measured by real time
      fluorescence quantification PCR technique. The cell growth curves were detected
      by Real Time Cell Electronics Sensing. RESULTS: 300 microg/ml of astragalus
      polysaccharides suppressed LX-2 cell proliferation (P<0.05, in 94.7 h), while
      astragalosides induced an significant cell proliferation (P<0.05) both at lower
      and higher concentration. 25 microg/ml astragalus polysaccharides and
      astragalosides induced TGF-beta1 expression. For other cytokines, astragalus
      polysaccharides induced a 104.9 fold higher expression of MMP2, while
      astragalosides induced a 550.65 fold higher expression of IL-10. Astragalus
      polysaccharides at 300 microg/ml concentration exhibited an inhibition effect on
      TGF-beta1, HGF, MMP9 and IL-10 mRNA expression, while up-regulated MMP2 mRNA
      expression. Astragalosides at 300 mug/ml concentration inhibited TGF-beta1 mRNA
      expression, while up-regulated MMP2, MMP9 and IL-10 mRNA expression. CONCLUSION:
      The anti-fibrosis function of astragalus polysaccharides might be associated with
      up-regulation of MMP2 expression, while that of astragalosides with up-regulation
      of MMP2, MMP9 and IL-10 expression.

PMID- 18067227
TI  - [Human papillomavirus infection in women with cervical lesion of Huzhou area of
      Zhejiang province].
AB  - OBJECTIVE: To observe human papillomavirus (HPV) infection in women with cervical
      lesions in Huzhou area of Zhejiang province. METHODS: 720 samples of cervical
      secretion or exfoliated cells were collected from women with cervical lesion in
      Huzhou area. Human papillomavirus was detected by suspension array technique.
      RESULTS: Positive HPV infection was detected in 25.42% cases (183/720), with 135
      cases of single HPV type, 33 of dual HPV types and 15 of multiple HPV types.
      HPV16 and HPV58 were the most prevalent types in 183 HPV positive cases.
      CONCLUSION: The most prevalent high-risk types of HPV are HPV16 and HPV58 in
      Huzhou area of Zhejiang province.

PMID- 18067228
TI  - [PD-1 expression in peripheral T cells of patients with HBV infection and its
      significance].
AB  - OBJECTIVE: To analyze the expression levels of PD-1 (program death factor-1) in
      peripheral T cells from patients infected with HBV, and to investigate its
      relationship with HBV serological markers. METHODS: A total of 65 HLA-A2+
      subjects, including 31 patients with chronic hepatitis B (CHB), 9 with acute
      resolved hepatitis B (AHB), 15 with HBV related liver cirrhosis (LC) and 10
      healthy blood donators, were enrolled. The expression of PD-1 in peripheral T
      cells and PD-1 ligands PD-L1 and PD-L2 in PBMCs were determined by relative
      quantitative real-time PCR. The serum HBV markers, HBV DNA load and liver
      function were also measured. RESULTS: Taken the PD-1 and PD-ligands expression in
      normal controls as a baseline level, the expression of PD-1 and PD-L1 from CHB
      patients was significantly increased, while the expression of PD-L2 was
      relatively low in all groups. In CHB patients, the PD-1 expression in peripheral
      T cells from patients with high viral load was much higher than that from those
      with low viral load or from normal controls. And the PD-1 expression level
      positively correlated with serum HBV DNA load (r=0.41, P<0.01) but not with serum
      ALT level. CONCLUSION: Long-term exposure to HBV antigens in CHB patients may
      increase the expression of PD-1 in T cells and thus leads to the virus persistent
      infection.

PMID- 18067229
TI  - [Association of p53 polymorphisms and its haplotypes with susceptibility of
      breast cancer].
AB  - OBJECTIVE: To investigate the association of p53 polymorphisms with
      susceptibility to breast cancer in Chinese Han population. METHODS: In this
      population-based case-control study, 84 cases with breast cancers and 168
      controls, matched to the cases in terms of gender, habitation and age (5 years),
      were genotyped for codon 72, intron 3, and intron 6 polymorphisms in p53 gene by
      polymerase chain reaction-restriction-fragment length polymorphism (PCR-RFLP)
      methods. The haplotype distribution was estimated and compared by EH linkage
      software 1. 2. RESULTS: The distributions of age, alcohol drinking, family
      history of cancer in first and second relatives were not significantly different
      between cases and controls. There was significant association between cigarette
      smoking and breast cancer (chi(2)=6.455, P=0.018), the percentage of ever or
      current smokers was significantly higher in cases (7.1 %) than that in controls
      (1.2%). The distributions of allelotype and genotype of codon72, intron 3, and
      intron 6 were also not significantly different between cases and controls
      (P>0.05). No significant association was found between the risk of breast cancer
      and p53 polymorphisms. The genetic linkage disequilibrium existed in these three
      polymorphic sites in controls, and the Arg-A-G and Pro-A-G were the most common
      haplotypes both in cases and controls. There was no significant association of
      p53 haplotype with risk of breast cancer. CONCLUSION: p53 codon72, intron 3, and
      intron 6 polymorphisms may not be associated with the susceptibility of breast
      cancer. The Arg-A-G and Pro-A-G haplotypes are the most common haplotypes in
      Chinese Han population.

PMID- 18067230
TI  - [Effect of postconditioning on rat hearts suffered from long-term hypothermic
      preservation].
AB  - OBJECTIVE: To assess the effect of postconditioning on cardiac protection of rat
      hearts suffered from long-term hypothermic preservation. METHODS: The Langendorff
      model of isolated rat heart was used. After 30 min of stabilization, the hearts
      were stored in 4 degrees C Celsior solution for 3 or 5 h followed by 60 min of
      reperfusion. Postconditioning was initiated by 3 cycles of 30 s ischemia followed
      by 30 s reperfusion at the beginning of subsequent persistent reperfusion. The
      recovery of cardiac contractile function and arrhythmia score were observed.
      RESULTS: (1) Compared with control group, postconditioning increased the recovery
      of heart rate (HR), left ventricular systolic pressure (LVDP), maximal rise/fall
      rate of ventricular pressure (dP/dt(max)) and coronary flow (CF) and rate
      pressure product (RPP) during reperfusion after 3 h of hypothermic preservation.
      However, left ventricular end-diastolic pressure (LVEDP) and the cardiac
      arrhythmia score during the first 10 min of reperfusion was significantly lower
      in 3 h postconditioning group than that in 3 h control group. (2) The rat hearts
      treated by postconditioning with 5-HD(100 micromol/L) abolished the amelioration
      of contract function induced by postconditioning. And it could also increase the
      cardiac arrhythmia score. (3) Compared with 5 h control group, the HR,
      LVDP,dP/dt(max), CF, LVEDP, RPP and the cardiac arrhythmia score were not
      significantly different in postconditioning treated hearts during reperfusion
      after 5 h of hypothermic preservation. CONCLUSION: Postconditioning could provide
      the cardiac protection on 3 h hypothermic preserved rat hearts,but not on 5 h
      hypothermic preserved rat hearts. The cardiac protection effect might be partly
      associated with activation of selective mitochondrial ATP-sensitive potassium
      channel.

PMID- 18067231
TI  - [N-acetyl-l-cysteine improves function of islet beta cell in hyperlipidemic rats
      and its mechanism].
AB  - OBJECTIVE: To investigate the effect of N-acetyl-l-cysteine (NAC) on islet beta
      cell function in hyperlipidemic rats and its mechanism. METHODS: Fifty-nine male
      SD rats of 8 week old were randomly divided into 3 groups: normal diet group(NC,
      n=20), high fat diet group (HF, n=20) and NAC treated group (NAC, n=19, NAC 300
      mg x kg(-1) x d(-1) and high fat diet). At the end of 20 weeks, fasting serum
      insulin (Ins), glucose(Glu), malonaldehyde (MDA) and reduced glutathione (GSH)
      were determined in plasma and pancreas tissue. The glucose infusion rate (GIR)
      was measured by euglycemic hyperinsulinemia clamp to evaluate the peripheral
      insulin resistance.Pancreatic islets were isolated and subjected to a perifusion
      medium containing 3.3 mmol/L glucose for 15 min, followed by 16.7 mmol/L glucose
      for 30 min, insulin content of perifusion medium was measured by RIA. The
      expressions of IRS-1, IRS-2, Glut-2 gene in islets were detected by real time
      PCR. RESULTS: (1)The insulin, glucose and MDA concentration in HF group were
      higher than those in NC group, but GSH levels in plasma and pancreas were lower.
      NAC intervention could reverse these effects. (2)The GIR was decreased
      significantly in HF group compared with NC group [(5.25 +/-1.2) Compared with
      (13.56 +/-1.7) mg x min(-1) x kg(-1), P<0.01], NAC intervention reversed these
      effect: GIR[(9.28 +/-1.50) Compared with (5.25 +/-1.2)mg x min(-1) x kg(-1),
      P<0.01]. (3) 16.7 mmol/L glucose increased the insulin secretion in the islet
      cells of the three groups, but the peak was lower in HF group. NAC intervention
      reversed these effects. (4) The gene expression of IRS-1 was significantly
      decreased by 42.3 % in HF group (P<0.05), and the expressions of IRS-2 and Glut-2
      were decreased by 28.1% and 22.9% (P<0.05) compared with NC group. In contrast,
      the expressions of IRS-1, IRS-2, Glut-2 in NAC group increased by 40.2%, 30.2%
      and 19.1%, respectively than those in HF group. CONCLUSION: NAC can reverse
      functional disorder of islet beta cells induced by high-fat-diet feeding. This
      antioxidant effect might be associated with upgrading gene expression of insulin
      signal transduction molecules in islet beta cells.

PMID- 18067232
TI  - [Construction of heparanase gene-targeted small interfering RNA and its gene
      silencing effect].
AB  - OBJECTIVE: To construct heparanase gene-targeted small interfering RNA(siRNA) and
      its expression vector and to observe its interference effect on the expression of
      heparanase gene in human malignant melanoma A375 cell. METHODS: Heparanase gene
      targeted hairpin siRNA was designed, two complementary oligonucleotide strand was
      synthesized and inserted into pRNATU6.1 vector, which was then identified by PCR
      and sequencing. Human malignant melanoma A375 cells were transfected with the
      constructed vector using lipofectamine method. Semi-quantitative PCR was
      performed to evaluate the heparanase-mRNA expression levels, and Western blot was
      performed to evaluate the expression of heparanase protein. RESULTS: The vector
      containing siRNA was identified by PCR and sequencing; the results of semi
      quantitative PCR and Western blot showed that the expression levels of both
      heparanase RNA and protein in transfected A375 cells were decreased
      significantly(P<0.05). CONCLUSION: The heparanase gene-targeted siRNA and its
      vector were successfully constructed, which can reduce the heparanase gene and
      protein expression in transfected cells.

PMID- 18067233
TI  - [Assembly of full-length human resistin gene in vitro and construction of its
      eukaryotic expression vector].
AB  - OBJECTIVE: To assemble the full-length of human resistin gene in vitro by using
      oligonucleotides and to construct its eukaryotic expression vector. METHODS:
      According to the gene sequence of resistin (GenBank: AF323081), 10
      oligonucleotides were designed and synthesized, followed by a touch down PCR to
      assemble the full-length gene. The PCR products were cloned into pSecTag2B vector
      and confirmed by sequencing. RESULTS: The band of PCR products and gene
      sequencing showed the insert fragment in pSecTag2B vector was identical to that
      as designed. CONCLUSION: The full-length of human resistin coding sequence was
      successfully assembled and amplified by touch down PCR, and a resistin-expressing
      eukaryotic vector was constructed.

PMID- 18067234
TI  - [Dendritic cells pulsed with glioma RNA induce immunity against intracranial
      gliomas].
AB  - OBJECTIVE: To investigate the anti-tumor effect of dendritic cells (DC) pulsed
      with G422 glioblastomas RNA in mice bearing intracranially G422 glioblastomas.
      METHODS: DCs were pulsed in vitro with glioblastomas G422 cell RNA. The tumor
      bearing mice were injected intratumorally or subcutaneously with pulsed DCs, PBS,
      non-pulsed DCs. The survival duration of mice was recorded. Serum levels of
      cytokine IFN-gamma, IL-2, IL-10, IL-4 were detected. Pathological examination was
      performed. RESULTS: The survival duration of mice with DC-based vaccine increased
      significantly(P<0.01). The serum IFN-gamma level was increased (P<0.01) and IL-10
      level was decreased (P<0.05) after treatment. Pathological examination showed
      necrotic tumor in the treatment mice. CONCLUSION: DC vaccination can
      significantly increase survival duration of mice with intratumoral or
      subcutaneous administration of vaccines.

PMID- 18067235
TI  - [Determination of residual organic solvents in Panax notoginseng extracts by
      capillary gas chromatography with headspace sampling].
AB  - OBJECTIVE: To develop a headspace gas chromatography method for the determination
      of residual organic solvents in Panax notoginseng extracts. METHODS: The samples
      were injected into HP-INNOWAX capillary column by headspace sampler and analyzed
      with FID detector using standard addition method. RESULTS: There was a good
      linearity in the experimental concentration (r=0.9932-0.9999). The rate of
      recovery was in the rang of 81.74%-111.2%. The numbers of theoretical plates were
      more than 15000 and the resolutions between the adjacent peaks were more than 2.
      The RSD of precision and accuracy were both less than 10 %. CONCLUSION: The
      method is simple,accurate and sensitive with good reproducibility, which can be
      used for the determination of the residual organic solvents in Panax notoginseng
      extracts.

PMID- 18067236
TI  - [Clinical efficacy of Nagata's techniques in auricular reconstruction for
      microtia].
AB  - OBJECTIVE: To analyze the clinical efficacy of Nagata;s techniques in auricular
      reconstruction for microtia. METHODS: One hundred and seventeen patients (120
      ears) with congenital microtia underwent auricular reconstruction mainly by
      Nagata;s techniques. RESULTS: All patients were followed up for 6 m approximately
      5 y (average 1 y) after surgery. The anatomic structure and appearance were
      satisfactory in all 120 reconstructed ears. CONCLUSIONS: Nagata's technique for
      auricular reconstruction is suitable to Asian patients with few complications,
      few stages and excellent reconstructed structure.

PMID- 18067237
TI  - [Surgical treatment for ventricular septal defect in infants under 5 kg of body
      weight].
AB  - OBJECTIVE: To review the indication and timing of surgery,surgical techniques and
      perioperative management of ventricular septal defect (VSD) repair on infants
      under 5 kg of body weight. METHODS: From January, 2000 to December, 2005, 134
      children patients with VSD and associated anomalies, who were under 5 kg of body
      weight and aged (3.9+/-1.9) months, were diagnosed and treated in our department.
      RESULTS: One case died of arrhythmia and heart failure in the early stage of
      postoperation (mortality 0.7%). The most common postoperative complications were
      pneumonia (14), pulmonary hypertensive crisis (6), arrhythmia (4), low cardiac
      output (4), dropsy of thoracic cavity(1). Followed up for 6 m-6 y, the
      development of all 133 cases was well. Two children with residual shunt got a
      spontaneous closure confirmed by echocardiography one year postoperatively.
      CONCLUSION: The clinical results of operations on VSD infants with low body
      weight are satisfactory with attention to the indication and timing of surgery,
      proper CPB management, rational operations and perioperative management.

PMID- 18067238
TI  - [Current status and perspective of hepatitis C virus models].
AB  - Lack of proper study models has brought difficulties in the study of the
      mechanism of viral infection, life cycle and pathogenic mechanism of hepatitis C
      virus (HCV) and also become the major obstacles in development of efficient
      vaccine and new drugs for hepatitis C. In recent years, the establishment of
      robust HCV cell culture infection system and HCV transgenic animal provide
      powerful tools for the analysis of host virus interactions, which facilitate the
      discovery of antiviral drugs and vaccines for this important human pathogen.

PMID- 18067239
TI  - [Research progress on Th17 cells].
AB  - Th17(T helper 17 cell), a newly discovered subset of T cells is associated with
      IL-23 and characterized by production of IL-17, the functions of which are
      distinct from those of Th1, Th2 and Treg subsets. The development of Th17 cells
      can be promoted by TGF-beta1, IL-6, and IL-23; but inhibited by IFN-gamma, IL-4
      and Socs3. It is clear that Th17 cells have protective effects on body by
      facilitating the pro-inflammatory responses. On the other hand, the role of Th17
      cells in the pathophysiology of autoimmune diseases has been described.

PMID- 18067240
TI  - [Allogeneic cord blood hematopoietic stem cell transplantation in two cases of
      children with leukemia].

PMID- 18067241
TI  - Effects of introduction of hydrophobic group on ribavirin base on mutation
      induction and anti-RNA viral activity.
AB  - One of the possible mechanisms of antiviral action of ribavirin (1-beta- d
      ribofuranosyl-1,2,4-triazole-3-carboxamide, 1) is the accumulation of mutations
      in viral genomic RNA. The ambiguous incorporation of 5'-triphosphate of ribavirin
      (RTP, 8) by a viral RNA-dependent RNA polymerase (RdRp) is a key step of the
      mutation induction. We synthesized three ribavirin analogues that possess
      hydrophobic groups, 4-iodo-1-beta- d-ribofuranosylpyrazole-3-carboxamide ( 7a), 4
      propynyl-1-beta- d-ribofuranosylpyrazole-3-carboxamide ( 7b), and 4-phenylethynyl
      1-beta-D-ribofuranosylpyrazole-3-carboxamide ( 7c), and the corresponding
      triphosphates ( 9a, 9b, and 9c, respectively). Steady-state kinetics analysis of
      the incorporation of these triphosphate analogues by a poliovirus RdRp, 3D (pol),
      revealed that while the incorporation efficiency of 9a was comparable to RTP, 9b
      and 9c showed lower efficiency than RTP. Antipolioviral activity of 7a and 7b was
      much more moderate than ribavirin, and 7c showed no antipolioviral activity.
      Effects of substituting groups on the incorporation efficiency by 3D (pol) and a
      strategy for a rational design of more active ribavirin analogues are discussed.

PMID- 18067242
TI  - Conformational comparisons of a series of tachykinin peptide analogs.
AB  - Previous studies have shown differences in the biological activity and the
      structure of two naturally occurring tachykinin peptides, substance P (SP,
      RPKPQQFFGLM-NH2) and ranatachykinin C (RTKC, HNPASFIGLM-NH2). To further
      understand the basis for these differences, four analogs that selectively
      incorporate the amino acid differences between SP and RTKC have been synthesized
      for study. The four peptide analogs studied have the following amino acid
      sequences: SP2-11, also known as des-Arg SP (PKPQQFFGLM-NH2); Q5A-SP (RPKPAQFFGLM
      NH2); Q6S-SP (RPKPQSFFGLM-NH2); and Q5AQ6S-SP (RPKPASFFGLM-NH2). Nuclear magnetic
      resonance spectroscopy and molecular modeling calculations were performed on SP,
      RTKC, SP2-11, Q5A-SP, Q6S-SP, and Q5AQ6S-SP to compare their conformational
      differences and similarities in the presence of the membrane mimetic system
      sodium dodecyl sulfate. The molecular modeling data of the analogs Q5A-SP and Q6S
      SP show residues 1-3 have a random conformation and residues 4-8 have a helical
      structure, while the C-terminus contains a poly C7 conformation that is similar
      to SP but different from RTKC. The molecular modeling data of the analogs SP2-11
      and Q5AQ6S-SP show a continuous helix conformation for residues 4-11 at the C
      terminus, which is different from SP but similar to RTKC. These structural
      differences are related to the functional differences of binding of the peptides
      at the SP receptor (NK1).

PMID- 18067243
TI  - Effect of pressure and temperature on the gelatinization of starch at various
      starch concentrations.
AB  - The effects of pressure, temperature, and treatment time on the degree of
      gelatinization were determined with differential scanning calorimetry
      measurements for wheat starch-water mixtures with starch concentrations varying
      between 5 and 80 w/w %. Although simple models could be used to describe the
      degree of starch gelatinization as a function of pressure or temperature, a more
      complex model based on the Gibbs energy difference had to be used to describe the
      degree of gelatinization as a function of both pressure and temperature. The
      experimental and model data were used to construct a phase diagram for 5, 30, and
      60 w/w % wheat starch-water mixtures. Data obtained from literature were in
      accordance with our phase diagrams. These phase diagrams can be used to estimate
      the degree of gelatinisation after applying a certain pressure and temperature on
      a starch-water mixture with starch concentrations in the range of 5 and 60 w/w %.

PMID- 18067244
TI  - Porphyrinmaleimides: towards thiol probes for cysteine residues in proteins.
AB  - Porphyrinmaleimides were synthesized and characterized. The thiol-containing
      amino acid L-cysteine reacted with 58% yield with these porphyrins to form
      bioconjugate adducts. The new thiol-active reagents were labeled cytoplasmic
      cysteine 140 and 316 in rhodopsin (Rh), a G protein coupled receptor (GPCR).

PMID- 18067245
TI  - Synthesis and evaluation in monkey of two sensitive 11C-labeled aryloxyanilide
      ligands for imaging brain peripheral benzodiazepine receptors in vivo.
AB  - We sought to develop (11)C-labeled ligands for sensitive imaging of brain
      peripheral benzodiazepine receptors (PBR) in vivo. Two aryloxyanilides with high
      affinity for PBR were identified and synthesized, namely, N-acetyl- N-(2
      methoxycarbonylbenzyl)-2-phenoxyaniline ( 3, PBR01) and N-(2-methoxybenzyl)- N-(4
      phenoxypyridin-3-yl)acetamide ( 10, PBR28). 3 was hydrolyzed to 4, which was
      esterified with [ (11)C]iodomethane to provide [ (11)C] 3. The O-desmethyl
      analogue of 10 was converted into [ (11)C] 10 with [ (11)C]iodomethane. [ (11)C]
      3 and [ (11)C] 10 were each injected into monkey to assess their brain kinetics
      with positron emission tomography (PET). After administration of either
      radioligand there was moderately high brain uptake of radioactivity. Receptor
      blocking and displacement experiments showed that a high proportion of this
      radioactivity was bound specifically to PBR. In monkey and rat, 3 and 10 were
      rapidly metabolized by ester hydrolysis and N-debenzylation, respectively, each
      to a single polar radiometabolite. [ (11)C] 3 and [ (11)C] 10 are effective for
      imaging PBR in monkey brain. [ (11)C] 10 especially warrants further evaluation
      in human subjects.

PMID- 18067246
TI  - Assigning significance to peptides identified by tandem mass spectrometry using
      decoy databases.
AB  - Automated methods for assigning peptides to observed tandem mass spectra
      typically return a list of peptide-spectrum matches, ranked according to an
      arbitrary score. In this article, we describe methods for converting these
      arbitrary scores into more useful statistical significance measures. These
      methods employ a decoy sequence database as a model of the null hypothesis, and
      use false discovery rate (FDR) analysis to correct for multiple testing. We first
      describe a simple FDR inference method and then describe how estimating and
      taking into account the percentage of incorrectly identified spectra in the
      entire data set can lead to increased statistical power.

PMID- 18067247
TI  - Clustering millions of tandem mass spectra.
AB  - Tandem mass spectrometry (MS/MS) experiments often generate redundant data sets
      containing multiple spectra of the same peptides. Clustering of MS/MS spectra
      takes advantage of this redundancy by identifying multiple spectra of the same
      peptide and replacing them with a single representative spectrum. Analyzing only
      representative spectra results in significant speed-up of MS/MS database
      searches. We present an efficient clustering approach for analyzing large MS/MS
      data sets (over 10 million spectra) with a capability to reduce the number of
      spectra submitted to further analysis by an order of magnitude. The MS/MS
      database search of clustered spectra results in fewer spurious hits to the
      database and increases number of peptide identifications as compared to regular
      nonclustered searches. Our open source software MS-Clustering is available for
      download at http://peptide.ucsd.edu or can be run online at
      http://proteomics.bioprojects.org/MassSpec.

PMID- 18067248
TI  - Modes of inference for evaluating the confidence of peptide identifications.
AB  - Several modes of inference are currently used in practice to evaluate the
      confidence of putative peptide identifications resulting from database scoring
      algorithms such as Mascot, SEQUEST, or X!Tandem. The approaches include
      parametric methods, such as classic PeptideProphet, and distribution free
      methods, such as methods based on reverse or decoy databases. Because of its
      parametric nature, classic PeptideProphet, although highly robust, was not highly
      flexible and was difficult to apply to new search algorithms or classification
      scores. While commonly applied, the decoy approach has not yet been fully
      formalized and standardized. And, although they are distribution-free, they like
      other approaches are not free of assumptions. Recent manuscripts by Kall et al.,
      Choi and Nesvizhskii, and Choi et al. help advance these methods, specifically by
      formalizing an alternative formulation of decoy databases approaches and
      extending the PeptideProphet methods to make explicit use of decoy databases,
      respectively. Taken together with standardized decoy database methods, and
      expectation scores computed by search engines like Tandem, there exist at least
      four different modes of inference used to assign confidence levels to individual
      peptides or groups of peptides. We overview and compare the assumptions of each
      of these approaches and summarize some interpretation issues. We also discuss
      some suggestions, which may make the use of decoy databases more computationally
      efficient in practice.

PMID- 18067249
TI  - Does trypsin cut before proline?
AB  - Trypsin is the most commonly used enzyme in mass spectrometry for protein
      digestion with high substrate specificity. Many peptide identification algorithms
      incorporate these specificity rules as filtering criteria. A generally accepted
      "Keil rule" is that trypsin cleaves next to arginine or lysine, but not before
      proline. Since this rule was derived two decades ago based on a small number of
      experimentally confirmed cleavages, we decided to re-examine it using 14.5
      million tandem spectra (2 orders of magnitude increase in the number of observed
      tryptic cleavages). Our analysis revealed a surprisingly large number of
      cleavages before proline. We examine several hypotheses to explain these
      cleavages and argue that trypsin specificity rules used in peptide identification
      algorithms should be modified to "legitimatize" cleavages before proline. Our
      approach can be applied to analyze any protease, and we further argue that
      specificity rules for other enzymes should also be re-evaluated based on
      statistical evidence derived from large MS/MS data sets.

PMID- 18067250
TI  - Online multidimensional separation with biphasic monolithic capillary column for
      shotgun proteome analysis.
AB  - A biphasic monolithic capillary column with 10 cm segment of strong-cation
      exchange monolith and 65 cm segment of reversed-phase monolith was prepared
      within a single 100 microm i.d. capillary. Separation performance of this column
      was evaluated by a five-cycle online multidimensional separation of 10 microg
      tryptic digest of yeast proteins using nanoflow liquid chromatography coupled
      with tandem mass spectrometry, and it took 12 h for whole separation under the
      operating pressure only approximately 900 psi. Totally, 780 distinct proteins
      were positively identified through assignment of 2953 unique peptides at false
      positive rate less than 1%. The good separation performance of this biphasic
      column was largely attributed to the good orthogonality of the strong-cation
      exchange monolith and reversed-phase monolith for multidimensional separation.

PMID- 18067251
TI  - False discovery rates and related statistical concepts in mass spectrometry-based
      proteomics.
AB  - Development of statistical methods for assessing the significance of peptide
      assignments to tandem mass spectra obtained using database searching remains an
      important problem. In the past several years, several different approaches have
      emerged, including the concept of expectation values, target-decoy strategy, and
      the probability mixture modeling approach of PeptideProphet. In this work, we
      provide a background on statistical significance analysis in the field of mass
      spectrometry-based proteomics, and present our perspective on the current and
      future developments in this area.

PMID- 18067252
TI  - Interaction of beta-lactoglobulin with resveratrol and its biological
      implications.
AB  - Beta-lactoglobulin (beta-LG), the major whey protein in the milk of ruminants,
      has a high affinity for a wide range of compounds. Resveratrol (3,5,4'
      trihydroxystilbene), a natural polyphenolic compound found in grapes and red
      wine, exhibits many physiological effects associated with health benefits. In
      this study, the interaction of resveratrol with beta-LG was investigated using
      circular dichroism, fluorescence and UV-vis absorbance. Self-association of
      resveratrol possibly occurs at high concentrations. Resveratrol interacts with
      beta-LG to form 1:1 complexes. Resveratrol is bound to the surface of the protein
      because beta-LG-bound polyphenol is in a weaker hydrophobic environment relative
      to 75% ethanol. The binding constant for the resveratrol-beta-LG interaction is
      between 10(4) and 10(6) M (-1), as determined by protein or polyphenol
      fluorescence. The beta-LG-resveratrol interaction may compete with self
      association of both the polyphenol and the protein. It has no apparent influence
      on beta-LG secondary structure but partially disrupts tertiary structure.
      Complexing with beta-LG provides a slight increase in the photostability of
      resveratrol and a significant increase in its hydrosolubility.

PMID- 18067253
TI  - Computer simulation of uranyl uptake by the rough lipopolysaccharide membrane of
      Pseudomonas aeruginosa.
AB  - Heavy metal environmental contaminants cannot be destroyed but require
      containment, preferably in concentrated form, in a solid or immobile form for
      recycling or final disposal. Microorganisms are able to take up and deposit high
      levels of contaminant metals, including radioactive metals such as uranium and
      plutonium, into their cell wall. Consequently, these microbial systems are of
      great interest as the basis for potential environmental bioremediation
      technologies. The outer membranes of Gram-negative microbes are highly
      nonsymmetric and exhibit a significant electrostatic potential gradient across
      the membrane. This gradient has a significant effect on the uptake and transport
      of charged and dipolar compounds. However, the effectiveness of microbial systems
      for environmental remediation will depend strongly on specific properties that
      determine the uptake of targeted contaminants by a particular cell wall. To aid
      in the design of microbial remediation technologies, knowledge of the factors
      that determine the affinity of a particular bacterial outer membrane for the most
      common ionic species found in contaminated soils and groundwater is of great
      importance. Using our previously developed model for the lipopolysaccharide (LPS)
      membrane of Pseudomonas aeruginosa, this work presents the potentials of mean
      force as the estimate of the free energy profile for uptake of sodium, calcium,
      chloride, uranyl ions, and a water molecule by the bacterial LPS membrane. A
      compatible classical parameter set for uranyl has been developed and validated.
      Results show that the uptake of uranyl is energetically a favorable process
      relative to the other ions studied. At neutral pH, this nuclide is shown to be
      retained on the surface of the LPS membrane through chelation with the carboxyl
      and hydroxyl groups located in the outer core.

PMID- 18067254
TI  - Thermo-responsive porous membranes of controllable porous morphology from
      triblock copolymers of polycaprolactone and poly(N-isopropylacrylamide) prepared
      by atom transfer radical polymerization.
AB  - Stimuli-responsive polymers are of crucial importance in the design of smart
      biomaterials. The thermo-responsive triblock copolymers of polycaprolactone (PCL)
      and poly( N-isopropylacrylamide) (P(NIPAAm)), or P(NIPAAm)- b-PCL- b- P(NIPAAm)
      copolymers, were synthesized in this work via atom transfer radical
      polymerization (ATRP). The P(NIPAAm)- b-PCL- b-P(NIPAAm) copolymers were cast by
      phase inversion in water into porous membranes with well-defined and uniformly
      distributed pores. The P(NIPAAm) content in the P(NIPAAm)- b-PCL- b- P(NIPAAm)
      copolymers and the temperature of the aqueous medium for phase inversion could be
      used to control the pore size and porosity of the membranes. The thermo
      responsive characteristics of the membranes were illustrated in the controlled
      water uptake and temperature-dependent glucose transport through the membranes.
      These temperature-sensitive membranes with controllable morphology have potential
      applications in biomedical engineering, drug delivery, and tissue engineering.

PMID- 18067255
TI  - Small-angle neutron scattering characterization of polyhydroxyalkanoates and
      their BioPEGylated hybrids in solution.
AB  - Small-angle neutron scattering was used to probe the molecular conformation of
      various polyhydroxyalkanoates (PHAs) and their bioPEGylated counterparts (PHA- b
      PEG). Analysis of neutron scattering profiles of these polymers dissolved in
      deuterated chloroform at various concentrations from dilute (approximately 0.1%
      w/v) to semidilute (approximately 7% w/v) showed the two distinct regimes and
      established overlap concentrations around 4-9 mg mL(-1). Scattering profiles were
      similar for all polymers investigated; power laws of approximately Q(-1.66) at
      high Q demonstrated that chloroform behaves as a good solvent for PHAs and
      suggests that under conditions synonymous with processing the solvated chains
      were swollen rather than in Gaussian conformation as previously reported. A
      gradual change to Guinier knees was followed by slopes of Q(-3) suggesting the
      presence of supramolecular structures at larger length scales. These observations
      in both the dilute and semidilute concentrations have not been previously
      reported. Zimm analysis of the data provided gyration radii and absolute
      molecular weights consistent with trends established using light scattering but
      showed some variation in their second virial coefficients. While natural
      synthetic hybrids of PHA- b-PEG can self-assemble into microporous films, they
      showed no noticeable differences in chain conformation when in solution, the
      fabricating medium. This suggests that some form of entropic inducement is
      required.

PMID- 18067256
TI  - Monitoring of hydroxyl groups in wood during heat treatment using NIR
      spectroscopy.
AB  - This paper deals with the evaluation of thermally treated wood by near-infrared
      (NIR) spectroscopy. In the NIR second derivative spectrum, the absorption band at
      6913 cm(-1) appeared with the procession of heat treatment, which conclusively
      assigned to the phenolic hydroxyl groups due to the lignin in comparison with the
      spectrum of acetylated spruce wood. As a result of the changes in the ratio of
      the areal integral calculated from spectral separation in the region of hydroxyl
      groups (7200-6100 cm(-1)) by the Gauss-Newton method, it was clear that the
      degradation of hydroxyl group in the cellulose started predominantly from the
      amorphous region and followed to semicrystalline and crystalline region. There
      was an obvious correlation between the weight decrement of wood and the decrement
      of hydroxyl groups in the cellulose by heat treatment.

PMID- 18067257
TI  - Viscoelastic behavior and in vivo release study of microgel dispersions with
      inverse thermoreversible gelation.
AB  - The dispersion of microgels with two interpenetrating polymer networks of poly( N
      isopropylacrylamide) and poly(acrylic acid) (PNIPAM-IPN-PAAc) has been studied
      for its viscoelastic behavior, biocompatibility, and in vivo release properties.
      The IPN microgels in water had an average hydrodynamic radius of about 85 nm at
      21 degrees C, measured by dynamic light scattering method. The atomic force
      microscope image showed that the particles were much smaller after they were
      dried but remained spherical shape. The storage and loss moduli ( G' and G'') of
      dispersions of IPN microgels were measured in the linear stress regime as
      functions of temperature and frequency at various polymer concentrations using a
      stress-controlled rheometer. For dispersions with polymer concentrations of 3.0
      and 6.0 wt % above 33 degrees C, the samples behave as viscoelastic solids and
      the storage modulus was larger than the loss modulus over the entire frequency
      range. The loss tangent was measured at various frequencies as a function of
      temperature. The gelation temperature was determined to be 33 degrees C at the
      point where a frequency-independent value of the loss tangent was first observed.
      At pH 2.5, when heated above the gelation temperature, IPN microgels flocculate
      by pumping a large amount of water from the gel. When the pH value was adjusted
      to neutral, deprotonation of -COOH groups on PAAc made the microgel keep water
      even above the gelation temperature. Using an animal implantation model, the
      biocompatibility and drug release properties of the IPN microgel dispersion were
      evaluated. Fluorescein as a model drug was mixed into an aqueous microgel
      dispersion at ambient temperature. This drug-loaded liquid was then injected
      subcutaneously in Balb/C mice from Taconic Farms. The test results have shown
      that the IPN microgels did not adversely promote foreign body reactions in this
      acute implantation model and the presence of gelled microgel dispersion
      substantially slowed the release of fluorescein.

PMID- 18067258
TI  - Influence of molecular weight and pH on adsorption of chitosan at the surface of
      large and giant vesicles.
AB  - This paper describes the mechanisms of adsorption of chitosan, a positively
      charged polyelectrolyte, on the DOPC lipid membrane of large and giant
      unilamellar vesicles (respectively, LUVs and GUVs). We observe that the variation
      of the zeta potential of LUVs as a function of chitosan concentration is
      independent on the chitosan molecular weight (Mw). This result is interpreted in
      terms of electrostatic interactions, which induce a flat adsorption of the
      chitosan on the surface of the membrane. The role of electrostatic interactions
      is further studied by observing the variation of the zeta potential as a function
      of the chitosan concentration for two different charge densities tuned by the pH.
      Results show a stronger chitosan-membrane affinity at pH 6 (lipids are negatively
      charged, and 40% chitosan amino groups are protonated) than at pH 3.4 (100% of
      protonated amino groups but zwitterionic lipids are positively charged) which
      confirms that adsorption is of electrostatic origin. Then, we investigate the
      stability of decorated LUVs and GUVs in a large range of pH (6.0 < pH < 12.0) in
      order to complete a previous study made in acidic conditions [Quemeneur et al.
      Biomacromolecules 2007, 8, 2512-2519]. A comparative study of the variation of
      the zeta potential as a function of the pH (2.0 < pH < 12.0) reveals a difference
      in behavior between naked and chitosan-decorated LUVs. This result is further
      confirmed by a comparative observation by optical microscopy of naked and
      chitosan-decorated GUVs in basic conditions (6.0 < pH < 12.0): at pH > 10.0, in
      the absence of chitosan, the vesicles present complex shapes, contrary to the
      chitosan-decorated vesicles which remain spherical, confirming thus that chitosan
      remains adsorbed on vesicles in basic conditions up to pH = 12.0. These results,
      in addition with our previous data, show that the chitosan-decorated vesicles are
      stable over a very broad range of pH (2.0 < pH < 12.0), which holds promise for
      their in vivo applications. Finally, the quantification of the chitosan
      adsorption on a LUV membrane is performed by zeta potential and fluorescence
      measurements. The fraction of membrane surface covered by chitosan is estimated
      to be lower than 40 %, which corresponds to the formation of a flat layer of
      chitosan on the membrane surface on an electrostatic basis.

PMID- 18067259
TI  - New intrinsically radiopaque hydrophilic microspheres for embolization: synthesis
      and characterization.
AB  - Polymeric particles currently used for embolization procedures have the
      disadvantage that they are radiolucent, that is, invisible on X-ray images, and
      consequently the interventional radiologist has to resort to angiography to
      (indirectly) monitor the fate of the particles. Here, we introduce intrinsically
      radiopaque hydrophilic microspheres. Since these microspheres can directly be
      visualized on X-ray images, using these microspheres for embolization purposes
      will allow superprecise location of the embolic material, both during and after
      the procedure. The microspheres, which are prepared by suspension polymerization,
      are based on the radiopaque monomer 2-[4-iodobenzoyl]-oxo-ethylmethacrylate and
      hydroxyethylmethacrylate (HEMA) and/or 1-vinyl-2-pyrrolidinone (NVP) as
      hydrophilic component. It has been shown that for clinically relevant X-ray
      visibility the spheres should contain at least 20 wt % iodine. At this iodine
      content, copolymerization with HEMA results in spheres that hardly imbibe water
      (EQ = 1.08). When HEMA is replaced by NVP, the volume swelling ratio can be
      significantly increased (to 1.33).

PMID- 18067260
TI  - Synthesis and characterization of novel biodegradable poly(carbonate ester)s with
      photolabile protecting groups.
AB  - Novel biodegradable poly(carbonate ester)s with photolabile protecting groups
      were synthesized by ring-opening copolymerization of L-lactide (LA) with 5-methyl
      5-(2-nitro-benzoxycarbonyl)-1,3-dioxan-2-one (MNC) with diethyl zinc (Et2Zn) as
      catalyst. The poly(L-lactide-co-5-methyl-5-carboxyl-1,3-dioxan-2-one) (P(LA-co
      MCC)) was obtained by UV irradiation of poly(L-lactide acid-co-5-methyl-5-(2
      nitro-benzoxycarbonyl)-1,3-dioxan-2-one) (P(LA-co-MNC)) to remove the protective
      2-nitrobenzyl group. The free carboxyl groups on the copolymers P(LA-co-MCC) were
      reacted with paclitaxel, a common antitumor drug. Gel permeation chromatography
      and NMR studies confirmed the copolymer structures and successful attachment of
      paclitaxel to the copolymer.

PMID- 18067261
TI  - Slowly digestible waxy maize starch prepared by octenyl succinic anhydride
      esterification and heat-moisture treatment: glycemic response and mechanism.
AB  - The mechanism and molecular structure of the slowly digestible waxy maize starch
      prepared by octenyl succinic anhydride (OSA) esterification and heat-moisture
      treatment were investigated. The in vitro Englyst test showed a proportion of
      28.3% slowly digestible starch (SDS) when waxy maize starch was esterified with
      3% OSA (starch weight based, and it is named OSA-starch), and a highest SDS
      content of 42.8% was obtained after OSA-starch (10% moisture) was further heated
      at 120 degrees C for 4 h (named HOSA-starch). The in vivo glycemic response of
      HOSA-starch, which showed a delayed appearance of blood glucose peak and a
      significant reduction (32.2%) of the peak glucose concentration, further
      confirmed its slow digestion property. Amylopectin debranching analysis revealed
      HOSA-starch had the highest resistance to debranching enzymes of isoamylase and
      pullulanase, and a simultaneous decrease of K m and V m (enzyme kinetics) was
      also shown when HOSA-starch was digested by either alpha-amylase or
      amyloglucosidase, indicating that the slow digestion of HOSA-starch resulted from
      an uncompetitive inhibition of enzyme activity during digestion. Size exclusion
      chromatography analysis of HOSA-starch showed fragmented amylopectin molecules
      with more nonreducing ends that are favorable for RS conversion to SDS by the
      action of amyloglucosidase in the Englyst test. Further solubility analysis
      indicates that the water-insolubility of HOSA-starch is caused by OSA-mediated
      cross-linking of amylopectin and the hydrophobic interaction between OSA-modified
      starch molecules. The water-insolubility of HOSA-starch would decrease its enzyme
      accessibility, and the digestion products with attached OSA molecules might also
      directly act as the uncompetitive inhibitor to reduce the enzyme activity leading
      to a slow digestion of HOSA-starch.

PMID- 18067262
TI  - Synthesis and characterization of silklike materials containing the calcium
      binding sequence from calbindin D9k or the shell nacreous matrix protein MSI60.

PMID- 18067263
TI  - Structurally colored thiol chitosan thin films as a platform for aqueous heavy
      metal ion detection.
AB  - Thin films of the polysaccharide chitosan and several chitosan derivatives,
      including conjugates of l-cysteine, thioglycolic acid, and 2-iminothiolane, were
      produced from dilute acidic solutions. Attempts to produce a fourth conjugate
      using lipoic acid resulted in the synthesis of partially N-acetylated chitosan
      ethanoate. These biopolymer films were exposed to solutions containing 50 ppm
      concentrations of various metal ion and counterion analytes. Analyte-induced
      changes in film thicknesses and refractive indices were measured using a
      spectroscopic ellipsometer, and shifts in film color were quantified using a
      reflectance spectrometer. The modified chitosans were generally more sensitive to
      change in response to pure water but also showed varied response to several ions
      of interest, including Cr(III) and Cr(VI), Hg(II), Ni(II), and others. The
      potential for tuning film response was demonstrated by varying the concentration
      of sulfur groups in the thioglycolic acid conjugate, leading to increased
      specificity for Hg(II).

PMID- 18067264
TI  - Antibacterial cellulose fiber via RAFT surface graft polymerization.
AB  - 2-(dimethylamino)ethyl methacrylate (DMAEMA) was polymerized from cellulosic
      filter paper via reversible addition-fragmentation chain transfer (RAFT)
      polymerization. The tertiary amino groups of the grafted PDMAEMA chains were
      subsequently quaternized with alkyl bromides of different chain lengths (C8-C16)
      to provide a large concentration of quaternary ammonium groups on the cellulose
      surface. The antibacterial activity of the quaternized and nonquaternized PDMAEMA
      grafted cellulosic fibers was tested against Escherichia coli. The antibacterial
      activity was found to depend on the alkyl chain length and on the degree of
      quaternization, i.e., the amount of quaternary amino groups present in the
      cellulose graft copolymers. The PDMAEMA-grafted cellulose fiber with the highest
      degree of quaternization and quaternized with the shortest alkyl chains was found
      to exhibit particularly high activity against E. coli.

PMID- 18067265
TI  - Bioresorbable and nonresorbable macroporous thermosensitive hydrogels prepared by
      cryopolymerization. Role of the cross-linking agent.
AB  - Macroporous poly( N-isopropylacrylamide) (pNIPA) gels (so-called cryogels), cross
      linked with different bis-acrylic compounds, N,N'-methylenebisacrylamide (MBAAm)
      and dimethacrylate-tyrosine-lysine-tyrosine (DMTLT), were prepared through free
      radical polymerization at subzero temperature in dioxane/water media. DMTLT is a
      hydrolytically degradable cross-linker with relatively hydrophobic character. The
      effects of different synthesis conditions, namely the concentration of monomers,
      the cross-linker, and the initiator in the reaction mixture, on the structure of
      the pNIPA-cryogels have been studied. The equilibrium swelling ratio of the DMTLT
      cross-linked pNIPA cryogels at temperatures below lower critical solution
      temperature (LCST) of pNIPA, was over ten times higher than that of the gels
      synthesized at room temperature from the same feed composition. The MBAAm cross
      linked pNIPA cryogels synthesized in water exhibited the highest equilibrium
      swelling and the fastest response. The critical transition temperature, T c, was
      lower ( T c approximately 31 degrees C) for pNIPA-cryogels synthesized in
      dioxane/water media or cross-linked with DMTLT as compared to MBAAm cross-linked
      pNIPA cryogels synthesized in water (T c approximately 33 degrees C). Scanning
      electron microscopy (SEM) revealed different porous structure and pore surface
      morphology depending on the cross-linker (MBAAm or DMTLT) and the solvent (water
      or dioxane/water) used. Gels and cryogels were also characterized by SAXS,
      showing that the nanostructure of the samples is related to swelling.

PMID- 18067266
TI  - Electrospun water-soluble carboxyethyl chitosan/poly(vinyl alcohol) nanofibrous
      membrane as potential wound dressing for skin regeneration.
AB  - Biocompatible carboxyethyl chitosan/poly(vinyl alcohol) (CECS/PVA) nanofibers
      were successfully prepared by electrospinning of aqueous CECS/PVA solution. The
      composite nanofibrous membranes were subjected to detailed analysis by scanning
      electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray
      diffraction (XRD). SEM images showed that the morphology and diameter of the
      nanofibers were mainly affected by the weight ratio of CECS/PVA. XRD and DSC
      demonstrated that there was strong intermolecular hydrogen bonding between the
      molecules of CECS and PVA. The crystalline microstructure of the electrospun
      fibers was not well developed. The potential use of the CECS/PVA electrospun
      fiber mats as scaffolding materials for skin regeneration was evaluated in vitro
      using mouse fibroblasts (L929) as reference cell lines. Indirect cytotoxicity
      assessment of the fiber mats indicated that the CECS/PVA electrospun mat was
      nontoxic to the L929 cell. Cell culture results showed that fibrous mats were
      good in promoting the cell attachment and proliferation. This novel electrospun
      matrix would be used as potential wound dressing for skin regeneration.

PMID- 18067267
TI  - Engineering cytochrome p450 enzymes.
AB  - The last 20 years have seen the widespread and routine application of methods in
      molecular biology such as molecular cloning, recombinant protein expression, and
      the polymerase chain reaction. This has had implications not only for the study
      of toxicological mechanisms but also for the exploitation of enzymes involved in
      xenobiotic clearance. The engineering of P450s has been performed with several
      purposes. The first and most fundamental has been to enable successful
      recombinant expression in host systems such as bacteria. This in turn has led to
      efforts to solubilize the proteins as a prerequisite to crystallization and
      structure determination. Lagging behind has been the engineering of enzyme
      activity, hampered in part by our still-meager comprehension of fundamental
      structure-function relationships in P450s. However, the emerging technique of
      directed evolution holds promise in delivering both engineered enzymes for use in
      biocatalysis and incidental improvements in our understanding of sequence
      structure and sequence-function relationships, provided that data mining can
      extract the fundamental correlations underpinning the data. From the very first
      studies on recombinant P450s, efforts were directed toward constructing fusions
      between P450s and redox partners in the hope of generating more efficient
      enzymes. While this aim has been allowed to lie fallow for some time, this area
      merits further investigation as does the development of surface-displayed P450
      systems for biocatalytic and biosensor applications. The final application of
      engineered P450s will require other aspects of their biology to be addressed,
      such as tolerance to heat, solvents, and high substrate and product
      concentrations. The most important application of these enzymes in toxicology in
      the near future is likely to be the biocatalytic generation of drug metabolites
      for the pharmaceutical industry. Further tailoring will be necessary for specific
      toxicological applications, such as in bioremediation.

PMID- 18067268
TI  - Strategies for the use of mixture-based synthetic combinatorial libraries:
      scaffold ranking, direct testing in vivo, and enhanced deconvolution by
      computational methods.

PMID- 18067269
TI  - Effectiveness of the suzuki-miyaura cross-coupling reaction for solid-phase
      peptide modification.
AB  - The Suzuki-Miyaura (SM) cross-coupling reaction has recently become one of the
      most efficient methods for C-C bond construction opening a wide range of
      opportunities in organic synthesis. This study focused on the evaluation of the
      use of the SM reaction to modify peptides using a solid-phase synthesis approach,
      an avenue that was still not investigated intensively. We used as a peptide model
      [Ala (1,2,3), Leu (8)]Enk linked to a polystyrene support on which it was
      previously assembled. The aromatic residues Tyr (4) and Phe (7) of [Ala (1,2,3),
      Leu (8)]Enk were respectively substituted with p-iodo-Phe, and an SM-related
      strategy was developed. Results indicated that the reaction conditions involving
      K 3PO 4 or Na 2CO 3 (base), DMF (solvent), Pd(PPh 3) 4 (catalyst), and
      temperatures ranging from 50 to 80 degrees C during 20 h were found as optimal.
      Finally applying those optimal conditions, a series of [Ala (1,2,3), Leu (8)]Enk
      analogs modified at Tyr (4) or Phe (7) positions was synthesized using diverse
      boronic acid derivatives.

PMID- 18067270
TI  - Solid-supported nitroso hetero-Diels-Alder reactions. 3. Acid-mediated
      transformation of cycloadducts by scission of the oxazine C-O bonds.
AB  - Polymer-supported dihydro[1,2]oxazine derivatives were prepared by acyl- and
      arylnitroso hetero-Diels-Alder reactions and exposed to strong (trifluoroacetic)
      acid during cleavage from resin-bound linkers. Cycloadducts prepared from cyclic
      dienes containing electron-donating substituents at the C6 oxazine carbon
      promoted formation of carbocations by cleavage of the C-O bond. The carbocations
      were quenched by nucleophilic reagents including triethylsilane, water, and
      alcohols and provided access to novel derivatives of N-alkyl hydroxamates.
      Products were submitted to biological assays, and the results are reported.

PMID- 18067271
TI  - Solid-supported nitroso hetero Diels-Alder reactions. 1. Acylnitroso dienophiles:
      scope and limitations.
AB  - Polymer-supported acylnitroso dienophiles were prepared and used in hetero Diels
      Alder (HDA) reactions with a variety of dienes. The transient acylnitroso
      dienophiles were prepared in situ from immobilized hydroxamates, which were
      attached to solid supports via several linkers each cleavable by different
      cleavage reagents, and served for the synthesis of both N-unsubstituted and N
      derivatized HDA adducts. Model compounds were used to (i) optimize reaction
      conditions for solid-supported HDA reactions, (ii) evaluate the outcome of the
      reactions with various dienes, (iii) compare relative reactivities of dienes, and
      (iv) assess the stability of HDA adducts toward cleavage conditions typically
      used in solid-phase syntheses. Cleaved products were submitted to biological
      assays, and the results are reported. The accompanying paper, focused on
      complementary arylnitroso HDA reactions, includes a comparison of both HDA
      reactions.

PMID- 18067272
TI  - Casein kinase 1alpha interacts with RIP1 and regulates NF-kappaB activation.
AB  - Tumor necrosis factor alpha (TNFalpha) triggers a signaling pathway converging on
      the activation of NF-kappaB, which forms the basis for many physiological and
      pathological processes. In a kinase gene screen using a NF-kappaB reporter, we
      observed that overexpression of casein kinase 1alpha (CK1alpha) enhanced TNFalpha
      induced NF-kappaB activation, and a CK1alpha kinase dead mutant, CK1alpha (K46A),
      reduced NF-kappaB activation induced by TNFalpha. We subsequently demonstrated
      that CK1alpha interacted with receptor interacting protein 1 (RIP1) but not with
      TRADD, TRAF2, MEKK3, IKKalpha, IKKbeta, or IKKgamma in mammalian cells. RIP1 is
      an indispensable molecule in TNFalpha/NF-kappaB signaling. We demonstrated that
      CK1alpha interacted with and phosphorylated RIP1 at the intermediate domain.
      Finally, we showed that CK1alpha enhanced RIP1-mediated NF-kappaB activation.
      Taken together, our studies suggest that CK1alpha is another kinase that
      regulates RIP1 function in NF-kappaB activation.

PMID- 18067273
TI  - Trigger factor assisted folding of green fluorescent protein.
AB  - Guanidine induced equilibrium and kinetic folding of a variant of green
      fluorescent protein (F99S/M153T/V163A, GFPuv) was studied. Using manual mixing
      and stopped-flow techniques, we combined different probes, including tryptophan
      fluorescence, chromophore fluorescence and reactivity with DTNB, to trace the
      spontaneous and TF-assisted folding of guanidine denatured GFPuv. We found that
      both unfolding and refolding of GFPuv occurred in a stepwise manner and a stable
      intermediate was populated under equilibrium conditions. The thermodynamic
      parameters obtained show that the intermediate state of GFPuv is quite compact
      compared to the denatured state and most of the green fluorescence is retained in
      this state. By studying GFPuv folding assisted by TF and a number of TF mutants,
      we found that wild-type TF catalyzes proline isomerization and accelerates the
      folding rate at low TF concentrations, but retards GFPuv folding and decelerates
      the folding rate at high TF concentrations. This reflects the two activities of
      TF, as an enzyme and as a chaperone. A general mechanism of TF assisted protein
      folding is discussed.

PMID- 18067274
TI  - Alternative modes of binding by U2AF65 at the polypyrimidine tract.
AB  - During initial recognition of an intron in pre-mRNA, the 3' end of the intron is
      bound by essential splicing factors. Notably, the consensus RNA sequences bound
      by these proteins are highly degenerate in humans. This raises the question of 3'
      splicing factor function in introns lacking canonical binding sites.
      Investigating the introns of the model organism Neurospora crassa revealed a
      different organization at the 3' end of the intron compared to most eukaryotic
      organisms. The predicted branch point sequences of Neurospora introns are much
      closer to the 3' splice site compared to those in human introns. In addition,
      Neurospora introns lack the canonical polypyrimidine tract found at the end of
      introns in most eukaryotic organisms. The large subunit of the U2 snRNP
      associated factor (U2AF65), which is essential for splicing of human introns and
      specifically recognizes the polypyrimidine tract, is also present in Neurospora.
      We show that Neurospora U2AF65 binds RNA with low affinity and specificity,
      apparently evolving with its disappearing binding site. The arginine/serine rich
      domain at the N-terminus of Neurospora U2AF65 regulates its RNA binding. We find
      that this regulated binding can be recapitulated in human U2AF65 which has been
      mutated to decrease both affinity and overall charge. Finally, we show that the
      addition of the small U2AF subunit (U2AF35) to U2AF65 with weakened RNA binding
      affinity significantly enhances the affinity of the resulting U2AF heterodimer.

PMID- 18067276
TI  - Thermodynamics and kinetics of glyoxal dimer formation: a computational study.
AB  - Density functional theory (B3LYP//6-311+G) calculations including Poisson
      Boltzmann implicit solvent were used to study the hydration of glyoxal and
      subsequent formation of dimeric species in solution. Our calculations show that
      the dioxolane ring dimer is the thermodynamic sink among all monomers and dimers
      with varying degrees of hydration. Although fully hydrated species are
      thermodynamically favored over their less hydrated counterparts, we find that a
      preliminary dehydration step precedes dimerization and ring closure. Ring closure
      of the open dimer monohydrate to the dioxolane ring dimer is kinetically favored
      over both hydration to the open dimer dihydrate and ring closure to form the
      dioxane ring dimer. The kinetic barriers for different geometric approaches for
      dimerization suggest an explanation why oligomerization stops after the formation
      of a dioxolane ring trimer as observed experimentally.

PMID- 18067277
TI  - Transition from moderate to strong hydrogen bonds: its identification and
      physical bases in the case of O-H...O intramolecular hydrogen bonds.
AB  - A systematic investigation aimed at identifying the transition from moderate (M)
      to strong (S) hydrogen bonds (HBs) and the physical bases of the main geometry
      based HB strength classifications reported in the literature has been undertaken
      using the quantum theory of atoms in molecules (QTAIM). Correlations between the
      Laplacian of the electron density (rho) at the O...H hydrogen bond critical
      points (HBCPs), nabla2rhohb, specifically between the more intuitive parameter
      Lhb = -nabla2rhohb and other QTAIM parameters, have also been explored. The
      transition from MHBs to SHBs has been identified as the minimum (maximum) in the
      geometric dependence of Lhb (nabla2rhohb). For O-H...O intramolecular (IM) HBs
      (including resonance-assisted HBs), the transition is obtained, in a truly
      remarkable agreement with the existing geometry-based HB strength
      classifications, when the O...O (O...H) distance is approximately 2.51 (
      approximately 1.55) A and when the ratio of the potential energy density (|Vhb|)
      to the kinetic energy density (Ghb) approximately 1.3. Accordingly, the ranges of
      the |Vhb|/Ghb ratios are >2-1.3 and 1.3-1 for, respectively, SHBs and MHBs. When
      the O...O distance is not a genuine indicator of HB strength, the |Vhb|/Ghb ratio
      and other parameters should be considered to characterize the strength of the
      HBs. Rationalizations have been provided by way of decoding the physical bases of
      the transition in terms of the properties of rho and the mechanical
      characteristics of the interactions that created the HBCPs. Lhb was found to
      correlate, with a very high degree of fidelity, with at least three parameters
      (in addition to O...O and O...H distances and the IMHB energy), Vhb/Ghb,
      Hhb/rhohb (the ratio of the total energy density, Hhb, to the electron density,
      rhohb (the so-called bond degree parameter)), and deltahb(O,H) (the
      delocalization index), demonstrating the importance and utility of Lhb
      (nabla2rhohb) for the study of HB interactions. A new refined energetics-based
      classification of O-H...O IMHB strengths has been advanced. The approach taken in
      this investigation can be extended to other HB systems.

PMID- 18067275
TI  - Identification of the molecular target of small molecule inhibitors of HDL
      receptor SR-BI activity.
AB  - Scavenger receptor, class B, type I (SR-BI), controls high-density lipoprotein
      (HDL) metabolism by mediating cellular selective uptake of lipids from HDL
      without the concomitant degradation of the lipoprotein particle. We previously
      identified in a high-throughput chemical screen of intact cells five compounds
      (BLT-1-5) that inhibit SR-BI-dependent lipid transport from HDL, but do not block
      HDL binding to SR-BI on the cell surface. Although these BLTs are widely used to
      examine the diverse functions of SR-BI, their direct target(s), SR-BI itself or
      some other component of the SR-BI pathway, has not been identified. Here we show
      that SR-BI in the context of a membrane lipid environment is the target of BLT-1,
      -3, -4, and -5. The analysis using intact cells and an in vitro system of
      purified SR-BI reconstituted into liposomes was aided by information derived from
      structure-activity relationship (SAR) analysis of the most potent of these BLTs,
      the thiosemicarbazone BLT-1. We found that the sulfur atom of BLT-1 was crucially
      important for its inhibitory activity, because changing it to an oxygen atom
      resulted in the isostructural, but essentially inactive, semicarbazone derivative
      BLT-1sc. SAR analysis also established the importance of BLT-1's hydrophobic
      tail. BLTs and their corresponding inactive compounds can be used to explore the
      mechanism and function of SR-BI-mediated selective lipid uptake in diverse
      mammalian experimental models. Consequently, BLTs may help determine the
      therapeutic potential of SR-BI-targeted pharmaceutical drugs.

PMID- 18067278
TI  - Nonlinear response properties of ultralarge hyperpolarizability twisted pi-system
      donor-acceptor chromophores. Dramatic environmental effects on response.
AB  - State-average complete active space self-consistent field (SA-CASSCF)
      calculations are performed on the energetically lowest two electronic states of a
      novel alkyl-substituted 4-quinopyran twisted pi-system electro-optic chromophore.
      In the gas phase, the ground-state electronic configuration is diradicaloid (D),
      and the first excited state is zwitterionic (Z). When an external dipolar field
      is applied to simulate polar solvation, the relative energies of D and Z are
      dramatically perturbed. At sufficient field strengths, the relative ordering of
      the states is inverted so that Z becomes the ground state. As the energy
      difference between the D and Z states falls, the magnitudes of the longitudinal
      static polarizability (alpha) and hyperpolarizability (beta) increase appreciably
      -in certain cases, by 2 orders of magnitude. These computational results are
      interpreted and supported by qualitative state correlation diagrams constructed
      from qualitative molecular orbital theory and are in agreement with recent
      experimental results on twisted pi-system electro-optic chromophores (Kang, H. et
      al. J. Am. Chem. Soc. 2007, 129, 3267). The computational results also suggest
      that changing the environmental polarity is a promising strategy for tuning alpha
      and beta in such types of chromophores, which experimentally exhibit large
      nonlinear optical response.

PMID- 18067279
TI  - Excitation wavelength-dependent electron-phonon and electron-vibrational coupling
      in the CP29 antenna complex of green plants.
AB  - Electron-phonon and electron-vibrational coupling strengths of a weakly
      (excitonically) coupled chlorophyll a S1-->S0 transition of the CP29 antenna
      complex of plant photosystem II were studied by difference fluorescence-line
      narrowing spectroscopy at 4.5 K. A strong, almost linear increase of the electron
      phonon coupling strength toward longer wavelengths was observed, with Huang-Rhys
      factors Sph increasing from 0.41+/-0.05 at 680 nm to about 0.66+/-0.07 at 688 nm.
      The former and latter wavelengths are located close to the peak and on the red
      edge of the inhomogeneous site distribution function, respectively. The
      experimentally obtained wavelength dependence of Sph may originate either from an
      alteration of the electron-phonon coupling strength by the local environment of
      the fluorescing chromophore and/or from the presence of two isoforms of CP29,
      which are characterized by different coupling strengths to the protein
      environment. The one-phonon profile peaks at omegam=22 cm(-1) and is described by
      an asymmetric function composed of a Gaussian low-energy wing and a Lorentzian
      high-energy tail with half-widths at half-maximum of 10+/-1 and 60+/-10 cm(-1),
      respectively. Thirty-nine individual vibrational modes between 90 and 1665 cm(-1)
      were resolved, and their Huang-Rhys factors were determined, which fall in the
      range between 0.0004 and 0.032. The broad feature present in the overlap region
      of phonon and vibrational modes at about 90 cm(-1) is characterized by S=0.048.
      An integral value of vibrational coupling strengths Svib=0.36+/-0.05 was
      determined, which is similar to that observed earlier for the trimeric LHC II
      complex.

PMID- 18067280
TI  - Long-range proton transfer in aqueous Acid-base reactions.
AB  - We study the mechanism of proton transfer (PT) in the aqueous acid-base reaction
      between the photoacid 8-hydroxy-1,3,6-pyrenetrisulfonic acid (HPTS) and acetate
      by probing the vibrational resonances of HPTS, acetate, and the hydrated proton
      with femtosecond mid-infrared laser pulses. We find that PT takes place in a
      distribution of hydrogen-bound reaction complexes that differ in the number of
      water molecules separating the acid and the base. The number of intervening water
      molecules ranges from 0 to 5, which, together with a strongly distance-dependent
      PT rate, explains the observed highly nonexponential reaction kinetics. The
      kinetic isotope effect for the reaction is determined to be 1.5, indicating that
      tunneling does not play a significant role in the transfer of the proton. Rather,
      the transfer mechanism is best described in terms of the adiabatic PT picture as
      it has been formulated by Hynes and co-workers [Staib, A.; Borgis, D.; Hynes, J.
      T. J. Chem. Phys. 1995, 102, 2487. Ando, K.; Hynes, J. T. J. Phys. Chem. B 1997,
      101, 10464.], where solvent fluctuations play an essential role in forming the
      correct hydrogen-bond configuration and solvent polarization to facilitate PT.

PMID- 18067281
TI  - A facile method to fabricate ZnO hollow spheres and their photocatalytic
      property.
AB  - This paper presents a novel and facile method for the fabrication of ZnO hollow
      spheres. In this approach, zinc ions were first adsorbed onto the surfaces of
      sulfonated polystyrene core-shell template spheres, and then reacted with NaOH to
      form a ZnO crystal nucleus, which was followed by a growth step to form ZnO
      nanoshells. During the formation of ZnO nanoshells or later on, the template
      spheres were "dissolved" in the same media to obtain ZnO hollow spheres directly.
      Neither additional dissolution nor calcination process was needed in this method
      to remove the templates, and the reaction conditions were very mild: neither high
      temperature nor long time was needed. Transmission electron microscopy, scanning
      electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and
      Brunauer-Emmett-Teller analysis were used to investigate the morphology, surface
      composition, crystalline structure, specific surface area, and porosity of the
      ZnO hollow spheres, respectively. UV-visible spectra show that these ZnO hollow
      spheres had very good photocatalytic activity.

PMID- 18067283
TI  - Zinc carboxylate cluster formation in conjugated metallomacrocycles: evidence for
      templation.
AB  - A new [3 + 3] Schiff base macrocycle incorporating three N2O2 salphen-type
      binding sites and peripheral neopentyloxy substituents has been prepared. The
      incorporation of Zn2+ ions into this and related conjugated Schiff base
      macrocycles has been studied by NMR spectroscopy, mass spectrometry, and X-ray
      diffraction. When reacted with 7 equiv of zinc acetate, the macrocycles template
      the formation of heptanuclear complexes. Two tetranuclear Zn2+ complexes that are
      plausible intermediates in the assembly of the heptanuclear complexes have been
      isolated and structurally characterized. These reactive intermediates are
      promising substrates for the synthesis of polynuclear, mixed-metal clusters. We
      also demonstrate that this chemistry may be generalized to other bridging
      carboxylate ligands, such as methacrylate.

PMID- 18067285
TI  - Expanded sodalite-type metal-organic frameworks: increased stability and H(2)
      adsorption through ligand-directed catenation.
AB  - The torsion between the central benzene ring and the outer aromatic rings in
      1,3,5-tri-p-(tetrazol-5-yl)phenylbenzene (H3TPB-3tz) and the absence of such
      strain in 2,4,6-tri-p-(tetrazol-5-yl)phenyl-s-triazine (H3TPT-3tz) are shown to
      allow the selective synthesis of noncatenated and catenated versions of expanded
      sodalite-type metal-organic frameworks. The reaction of H3TPB-3tz with CuCl2.2H2O
      affords the noncatenated compound Cu3[(Cu4Cl)3(TPB-3tz)8]2.11CuCl2.8H2O.120DMF
      (2), while the reaction of H3TPT-3tz with MnCl2.4H2O or CuCl2.2H2O generates the
      catenated compounds Mn3[(Mn4Cl)3(TPT-3tz)8]2.25H2O.15CH3OH.95DMF (3) and
      Cu3[(Cu4Cl)3(TPT-3tz)8]2.xsolvent (4). Significantly, catenation helps to
      stabilize the framework toward collapse upon desolvation, leading to an increase
      in the surface area from 1120 to 1580 m2/g and an increase in the hydrogen
      storage capacity from 2.8 to 3.7 excess wt % at 77 K for 2 and 3, respectively.
      The total hydrogen uptake in desolvated 3 reaches 4.5 wt % and 37 g/L at 80 bar
      and 77 K, demonstrating that control of catenation can be an important factor in
      the generation of hydrogen storage materials.

PMID- 18067284
TI  - Luminescent biological probes derived from ruthenium(II) estradiol polypyridine
      complexes.
AB  - Four luminescent ruthenium(II) polypyridine estradiol complexes [Ru(NwedgeN)2(bpy
      estradiol)](PF6)2 (NwedgeN = 2,2'-bipyridine (bpy), 4,7-diphenyl-1,10
      phenanthroline (Ph2-phen); bpy-estradiol = 5-(4-(17alpha
      ethynylestradiolyl)phenyl)-2,2'-bipyridine (bpy-ph-est), 4-(N-(6-(4-(17alpha
      ethynylestradiolyl)benzoylamino)hexyl)aminomethyl)-4'-methyl-2,2'-bipyridine
      (mbpy-C6-est)) have been designed as new luminescent biological probes. The
      lipophilicity and photophysical and electrochemical properties of these complexes
      have been investigated. Upon photoexcitation, all the complexes exhibited intense
      and long-lived triplet metal-to-ligand charge-transfer (3MLCT) (dpi(Ru) -->
      pi*(diimine)) emission in fluid solutions at 298 K and in low-temperature glass.
      The binding of the complexes to estrogen receptor-alpha (ERalpha) has been
      studied by emission titrations. The Ph2-phen complexes showed emission
      enhancement and increased lifetimes upon binding to the protein. Additionally,
      the cytotoxicity of the complexes toward the HeLa cell line has been examined by
      the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and
      the IC50 values ranged from 83.1 to 166.6 microM (cisplatin showed an IC50 value
      of 34.3 microM under the same experimental conditions). Furthermore, the cellular
      uptake of the complexes has been investigated by flow cytometry and laser
      scanning confocal microscopy.

PMID- 18067286
TI  - Ag(I)-based tectons for the construction of helical and meso-helical hydrogen
      bonded coordination networks.
AB  - The new ligand 4-(3-(2-pyridyl)pyrazol-1-ylmethyl)benzoic acid (L) has been
      prepared and characterized. This bifunctional ligand incorporates both a
      chelating region, with two nitrogen donors, suitable for chelating to soft
      transition metal ions, and a self-complementary hydrogen-bonding region which can
      facilitate intermolecular association of ligands or ligand-based complexes. X-ray
      structural analysis of the ligand shows it to adopt a one-dimensional helical
      polymeric structure, with adjacent ligands hydrogen bonded to each other.
      Reaction of L with silver(I) salts (AgOTf (1, 1.1.5H(2)O), AgNO(3) (2), AgPF6
      (3.CH(3)OH), and AgClO(4) (4.CH(3)OH)) results in the formation of complexes with
      2:1 stoichiometries. X-ray structural analysis of these complexes shows that, in
      each case, one-dimensional chain structures are obtained where chiral AgL(2)
      tectons are hydrogen bonded together, either directly or mediated by anions or
      solvent. Structures with either helical or meso-helical structures are observed.

PMID- 18067287
TI  - A three-dimensional open-framework indium selenide: [C(7)H(10)N][In(9)Se(14)].
AB  - An open-framework indium selenide, [C7H10N][In9Se14], has been prepared under
      solvothermal conditions in the presence of 3,5-dimethylpyridine and characterized
      by single-crystal X-ray diffraction, thermogravimetry, elemental analysis,
      Fourier tranform IR spectroscopy, and UV-vis diffuse reflectance. The crystal
      structure of [C7H10N][In9Se14] contains an unusual building unit, in which corner
      and edge-linked InSe45- tetrahedra coexist. The presence of one-dimensional
      circular channels, of ca. 6 A diameter, results in approximately 25% of solvent
      accessible void space.

PMID- 18067288
TI  - First correlation of nanoparticle size-dependent formation with the ionic liquid
      anion molecular volume.
AB  - Stable silver nanoparticles are obtained reproducibly by hydrogen reduction of
      different inorganic precursors from AgIX salts (X = BF4, PF6, OTf) dissolved in
      the ionic liquids BMim+BF4-, BMim+PF6-, BMim+OTf-, or BtMA+NTf2- [BMim+ = n
      butylmethylimidazolium, BtMA+ = n-butyltrimethylammonium, NTf2 = N(O2SCF3)2, and
      OTf = O3SCF3] in the presence of n-butylimidazole (Bim) as the scavenger for the
      HX acid byproduct and with a narrow size distribution in the diameter range of
      2.8-26.1 nm, which increases linearly with the molecular volume of the ionic
      liquid anion (transmission electron microscopy characterization).

PMID- 18067289
TI  - Characterization of platinum anticancer drug protein-binding sites using a top
      down mass spectrometric approach.
AB  - A proof-of-principle study on the application of a top-down electrospray
      ionization Fourier transform ion cyclotron resonance mass spectrometric approach
      for characterization of the primary binding sites of the platinum anticancer
      agents cisplatin, transplatin, and oxaliplatin on ubiquitin is presented. Through
      employment of different fragmentation techniques, the binding sites of cisplatin
      and oxaliplatin were found at N-terminal methionine-containing ubiquitin
      fragments, while transplatin was observed to be attached to 19Pro-Ser-Asp-Thr-Ile
      Glu24. The binding to proteins is of particular relevance for the mode of action
      of metallodrugs with regard to (de)activation, transport, excretion, etc. To the
      best of our knowledge, this is the first top-down mass spectrometric study on the
      protein binding site characterization of transition-metal anticancer agents and
      demonstrates the potential of the applied technique for investigating metal drug
      protein interactions.

PMID- 18067290
TI  - Spectroscopic characterization of photolytically generated radical ion pairs in
      single-wall carbon nanotubes bearing surface-immobilized tetrathiafulvalenes.
AB  - We succeeded in establishing for the first time a conclusive spectroscopic
      signature for reduced single-wall carbon nanotubes (SWNT), which evolves from
      electron donor-acceptor interactions between SWNT and electron-donating pi
      extended tetrathiafulvalene (exTTF). In particular, pi-pi interactions were
      employed to anchor the electron donor to the surface of SWNT. New conduction band
      electrons, injected from photoexcited exTTF, shift the transitions that are
      associated with the van Hove singularities to lower energies.

PMID- 18067291
TI  - Does the "superatom" exist in halogenated aluminum clusters?
AB  - We have shown that Aln clusters do not show any characteristics of a superatom in
      halogenated aluminum clusters. The enhanced stability of halogenated Al clusters
      can be explained by the magic nature of the clusters, not by superatom chemistry.
      The presence of even a few electronegative elements provides significant
      perturbation to the molecular orbitals of Al clusters and stabilizes the
      electropositive Al cluster cores, closely correlating with metal cluster-ligand
      chemistry. Our work provides significant chemical insights into the understanding
      of the structure and stability of halogenated aluminum clusters, and these new
      insights are applicable to other metal cluster-ligand systems.

PMID- 18067293
TI  - Rapid bioenabled formation of ferroelectric BaTiO3 at room temperature from an
      aqueous salt solution at near neutral pH.
AB  - A 12-mer peptide, identified through phage display biopanning, has been used for
      the first time to induce the rapid formation of ferroelectric (tetragonal)
      nanocrystalline BaTiO3 at room temperature from an aqueous salt precursor
      solution at near neutral pH. BaTiO3 is widely used in capacitors, thermistors,
      displays, and sensors owing to its attractive dielectric, ferroelectric,
      pyroelectric, optical, and electrochemical properties. Two 12-mer peptides (BT1
      and BT2) were selected from a phage-displayed peptide library via binding to
      tetragonal BaTiO3 powder. While these peptides possessed various types of amino
      acids, 8 of the 12 amino acids were common to both peptides. Each of these
      peptides induced the formation of faceted nanoparticles (50-100 nm diameter) from
      an aqueous precursor solution. X-ray diffraction and selected area electron
      diffraction patterns obtained from these faceted nanoparticles were consistent
      with the BaTiO3 compound. Rietveld analyses of the X-ray diffraction patterns
      yielded good fits to tetragonal crystal structures, with the BaTiO3 formed in the
      presence of the BT2 peptide exhibiting the most tetragonal character. A coating
      of the latter BaTiO3 nanoparticles exhibited polarization hysteresis (a well
      known characteristic of ferroelectric materials) at room temperature and a
      relative permittivity of 2200. Such rapid, peptide-induced precipitation at room
      temperature provides new opportunities for direct BaTiO3 formation on low-melting
      or reactive materials (e.g., plastics, cloths, bio-organics) and the low
      temperature integration of BaTiO3 into electronic devices (e.g., on silicon or
      flexible polymer substrates).

PMID- 18067292
TI  - Selecting folded proteins from a library of secondary structural elements.
AB  - A protein evolution strategy is described by which double-stranded DNA fragments
      encoding defined Escherichia coli protein secondary structural elements (alpha
      helices, beta-strands, and loops) are assembled semirandomly into sequences
      comprised of as many as 800 amino acid residues. A library of novel polypeptides
      generated from this system was inserted into an enhanced green fluorescent
      protein (EGFP) fusion vector. Library members were screened by fluorescence
      activated cell sorting (FACS) to identify those polypeptides that fold into
      soluble, stable structures in vivo that comprised a subset of shorter sequences (
      approximately 60 to 100 residues) from the semirandom sequence library.
      Approximately 108 clones were screened by FACS, a set of 1149 high fluorescence
      colonies were characterized by dPCR, and four soluble clones with varying amounts
      of secondary structure were identified. One of these is highly homologous to a
      domain of aspartate racemase from a marine bacterium (Polaromonas sp.) but is not
      homologous to any E. coli protein sequence. Several other selected polypeptides
      have no global sequence homology to any known protein but show significant alpha
      helical content, limited dispersion in 1D nuclear magnetic resonance spectra, pH
      sensitive ANS binding and reversible folding into soluble structures. These
      results demonstrate that this strategy can generate novel polypeptide sequences
      containing secondary structure.

PMID- 18067294
TI  - Total synthesis of (+/-)-merrilactone A.
AB  - The total synthesis of racemic merrilactone A (a neurotrophic agent) is
      described, featuring simultaneous and stereospecific creation of the C4 and C5
      stereocenters via a notable silyloxyfuran Nazarov cyclization. Full details of
      the successful synthetic strategy are given, as well as several examples of the
      interesting reactivity of intermediates that were prepared and studied during the
      execution of the total synthesis. A detailed investigation of the Lewis acid
      catalyzed Nazarov cyclization of silyloxyfurans was conducted, including a
      systematic study of substrate scope and limitations. In addition, experiments
      were conducted that suggest the participation of Lewis acidic silicon species in
      the Nazarov cyclization.

PMID- 18067295
TI  - 2D correlation deep UV resonance raman spectroscopy of early events of lysozyme
      fibrillation: kinetic mechanism and potential interpretation pitfalls.
AB  - The early stages of hen egg white lysozyme (HEWL) fibrillation were
      quantitatively characterized by two-dimensional correlation deep UV resonance
      Raman spectroscopy (2D-DUVRR) in terms of the sequential order of events and
      their characteristic times. The evolution of individual secondary structural
      elements was established through the correlation between Amide I, Amide III, and
      Calpha-H bending Raman bands. The temporal order of tertiary and individual
      secondary structural changes was probed through the cross-correlation of
      phenylalanine and Amide Raman bands. Both the sequential order and the
      characteristic times of tertiary and secondary structural changes allowed for
      reconstructing the molecular mechanism of lysozyme structural changes at the
      early stages of fibrillation. The 2D-DUVRR analysis of our data indicated that
      melting of the alpha-helix happened after the formation of the disordered
      structure, which was termed as apparent inverse order of secondary structural
      changes. We demonstrated that this apparent inverse order of events is typical
      for all chemical reactions involving the formation of intermediate(s), which may
      lead to the serious misinterpretation of 2D correlation results. We proposed a
      new simulation-aided approach for reconstructing and quantitatively
      characterizing the reaction mechanism of a (bio)chemical reaction that accounts
      for the apparent inverse order of events.

PMID- 18067297
TI  - Synthesis and use of mechanism-based protein-profiling probes for retaining beta
      D-glucosaminidases facilitate identification of Pseudomonas aeruginosa NagZ.
AB  - The NagZ class of retaining exo-glucosaminidases play a critical role in
      peptidoglycan recycling in Gram-negative bacteria and the induction of resistance
      to beta-lactams. Here we describe the concise synthesis of 2-azidoacetyl-2-deoxy
      5-fluoro-beta-d-glucopyranosyl fluoride as an activity-based proteomics probe for
      profiling these exo-glycosidases. This active-site directed reagent covalently
      inactivates this class of retaining N-acetylglucosaminidases with exquisite
      selectivity by stabilizing the glycosyl-enzyme intermediate. Inactivated Vibrio
      cholerae NagZ can be elaborated with biotin or a FLAG-peptide epitope using the
      Staudinger ligation or the Sharpless-Meldal click reaction and detected at
      nanogram levels. This ABPP enabled the profiling of the Pseudomonas aeruginosa
      proteome and identification at endogenous levels of a tagged protein with
      properties consistent with those of PA3005. Cloning of the gene encoding this
      hypothetical protein and biochemical characterization enabled unambiguous
      assignment of this hypothetical protein as a NagZ. The identification and cloning
      of this NagZ may facilitate the development of strategies to circumvent
      resistance to beta-lactams in this human pathogen. As well, this general
      strategy, involving such 5-fluoro inactivators, may prove to be of general use
      for profiling proteomes and identifying glycoside hydrolases of medical
      importance or having desirable properties for biotechnology.

PMID- 18067296
TI  - Modulation of water exchange in europium(III) DOTA-tetraamide complexes via
      electronic substituent effects.
AB  - The chemical exchange saturation transfer (CEST) efficiency for a series Eu3+
      based tetraamide complexes bearing p-substituents on a single coordinating
      pendant arm is highly sensitive to water exchange rates. The CEST effect
      increases in the order Me < MeO < F approximately CO2tBu < CN < H. These results
      show that CEST contrast can be modulated by changes in electron density at a
      single ligating atom, and this forms the basis of creating imaging agents that
      respond to chemical oxidation and reduction.

PMID- 18067298
TI  - Hydrogen-deuterium exchange and selective labeling of deprotonated amino acids
      and peptides in the gas phase.
AB  - Hydrogen-deuterium exchange reactions of deprotonated amino acids and small
      peptides were studied. Selective labeling can be carried out at the alpha-amino
      group of lysine (2 of 4 labile hydrogens undergo exchange with CF3CH2OD) and the
      guanidine side chain of arginine (3 of 6 labile hydrogens undergo exchange with
      CH3CH2OD and C6H5CH2OD). Differential labeling of peptides also was accomplished,
      and the extent of H/D exchange is dependent on the amino acids which are present
      as well as their order in the chain.

PMID- 18067299
TI  - Semiconducting lead-sulfur-organic network solids.
AB  - The reactions of Pb(OAc)2 with 1,2,4,5-benzenetetrathiol, 1,4-benzenedithiol, and
      benzenehexathiol in ethylenediamine yield bright yellow [Pb2(S2C6H2S2)(en)]n,
      orange-red [Pb3(SC6H4S)3(en)2]n, and brown [Pb3C6S6]n, respectively. The
      structures of [Pb2(S2C6H2S2)(en)]n and [Pb3C6S6]n were solved by synchrotron X
      ray powder diffraction, while the structure of [Pb3(SC6H4S)3(en)2]n was solved by
      single-crystal X-ray diffraction. The bonding in [Pb2(S2C6H2S2)(en)]n indicates
      the presence of "molecular" units, while in [Pb3C6S6]n, the bonding most
      resembles that in an inorganic solid such as PbS. The differences in bonding are
      reflected in the optical and electrical properties of the materials; [Pb3C6S6]n
      is a semiconductor.

PMID- 18067300
TI  - Organolanthanide-based synthesis of 1,2,3-triazoles from nitriles and diazo
      compounds.
AB  - The reaction of [(C5Me5)2Ln][(mu-Ph)2BPh2] complexes with the lithium salt of
      (trimethylsilyl)diazomethane, Li[Me3SiCN2], gave products formulated as the
      dimeric isocyanotrimethylsilyl amide complexes {(C5Me5)2Ln[mu-N(SiMe3)NC]}2 (Ln =
      Sm, 1; La, 2). Reactions of (C5Me5)2Sm and [(C5Me5)2Sm(mu-H)]2 with Me3SiCHN2
      also form 1. Complexes 1 and 2 react with Me3CCN to form the 1,2,3-triazolato
      complexes (C5Me5)2Ln(NCCMe3)[NNC(SiMe3)C(CMe3)N] (Ln = Sm, 3; La, 4). Complex 2
      reacts with Me3SiN3 to make the isocyanide ligated azide complex
      {(C5Me5)2La[CNN(SiMe3)2](mu-N3)}3, 5.

PMID- 18067301
TI  - Hydrogen-bond acceptance of bifunctional ligands in an alkyne-metal pi complex.
AB  - Experiment and theory have been used to study reactive alkyne pi complexes,
      intermediates in anti-Markovnikov alkyne hydration by CpRu bis(phosphine)
      catalysts with heterocyclic substituents. Each heterocycle accepts a hydrogen
      bond from an acetylene C-H, as revealed by NMR coupling constants between alkyne
      13C and 1H nuclei as well as between alkyne 13C and pyridine 15N (2hJCN).
      Moreover, further alkyne transformations occur at temperatures from 50 to 90
      degrees C below what is needed to convert a control compound without the
      heterocycles.

PMID- 18067302
TI  - Design of a selective metal ion switch for self-assembly of peptide-based
      fibrils.
AB  - The self-assembling peptide TZ1H, a structural variant of the trimeric isoleucine
      zipper GCN4-pII, contains histidine residues at core d-positions of alternate
      heptads that define three trigonal coordination sites within the coiled-coil
      trimer. Circular dichroism spectropolarimetry indicated that peptide TZ1H
      undergoes a random coil to alpha-helical conformational change upon binding of 1
      equiv of silver(I) ion, but not zinc(II), copper(II), or nickel(II) ions.
      Isothermal titration calorimetry provided evidence for a single binding-site
      model in which each peptide contributes one net silver(I) coordination site, in
      agreement with the proposed structural model. Transmission electron microscopy
      revealed that TZ1H self-assembles into long aspect ratio helical fibers in the
      presence of silver(I) ion. These results demonstrate that the rational design of
      selective metal ion binding sites within de novo designed peptides represents a
      promising approach to the controlled fabrication of nanoscale, self-assembled
      materials.

PMID- 18067303
TI  - Fast enzyme dynamics at the active site of formate dehydrogenase.
AB  - The role of femtosecond-picosecond structural dynamics of proteins in enzyme
      catalyzed reactions is a hotly debated topic. We report infrared photon echo
      measurement of the formate dehydrogenase-NAD+-azide ternary complex. In contrast
      to earlier studies of protein dynamics, the data show complete spectral diffusion
      on the femtosecond-picosecond time scale with no static heterogeneity. This
      result indicates that this transition-state analogue complex completely samples
      the distribution of structures that determine the distribution of azide
      vibrational frequencies within a few picoseconds and that there are no slower
      motions that perturb the H-bond network at the active site.

PMID- 18067304
TI  - Multiple logic gates based on electrically wired surface-reconstituted enzymes.
AB  - The electrode functionalized with glucose oxidase (GOx) and microperoxidase-11
      (MP-11) performs various Boolean logic operations (OR, XOR, AND-OR) upon addition
      of glucose and/or H2O2 and application of different potentials. The output signal
      coming from the electrically wired enzymes is electrochemically readable,
      allowing interfacing of biochemical computing systems with ordinary electronics.

PMID- 18067305
TI  - Palladium-catalyzed direct C-h arylation of N-iminopyridinium ylides: application
      to the synthesis of (+/-)-anabasine.
AB  - Palladium-catalyzed direct C-H arylation of N-iminopyridinium ylides provides a
      powerful and versatile method for the synthesis of functionalized piperidines in
      good yields. Chemoselective functionalization of the pyridinium ring in the
      presence of a pyridine substituent is possible as exemplified by the expedient
      synthesis of anabasine in 61% overall yield over three steps.

PMID- 18067306
TI  - [3]rotaxane-porphyrin conjugate as a novel supramolecular host for fullerenes.
AB  - A new supramolecular host with good affinity toward fullerenes has been
      developed. This host having a tweezer-like shape is built on a [3]rotaxane
      scaffold and contains two free-base porphyrin moieties as recognition units for
      fullerenes. The ability of this tweezer to bind fullerenes strongly depends on
      the solvent system used and the size of fullerene.

PMID- 18067307
TI  - Tandem RCM-isomerization approach to glycals of desoxyheptoses from a common
      precursor.
AB  - Ring closing metathesis and tandem RCM-isomerization have been applied to the
      synthesis of six- to eight-membered oxacycles, starting from a common precursor.
      The products of the tandem RCM-isomerization sequence are glycals of 3
      deoxyheptoses of varying ring size.

PMID- 18067308
TI  - Highly diastereoselective addition of cinnamylzinc derivatives to alpha-chiral
      carbonyl compounds.
AB  - Cinnamylzinc reagents react with cyclic and acyclic alpha-chiral ketones under
      very mild conditions (-78 degrees C, 1 h), yielding the corresponding homoallylic
      alcohols bearing three adjacent stereocenters with high diastereoselectivity. An
      extension of this reaction to enantioenriched alpha-chiral ketones is also
      described.

PMID- 18067309
TI  - A helix-turn-helix supersecondary structure based on oligo(phenanthroline
      dicarboxamide)s.
AB  - An artificial helix-turn-helix (HTH) supersecondary structure based on the
      oligo(phenanthroline dicarboxamide)s, in which the 2,2'-dimethoxy-1,1'-binaphthyl
      6,6'-diamine subunit was utilized as the turn to impart a bias in the twist sense
      of the supersecondary structure, was reported. The HTH structure has been
      demonstrated by UV/vis, NMR, CD spectra, and X-ray crystal analysis.

PMID- 18067310
TI  - Anti aldol selectivity in a synthetic approach to the C1-C12 fragment of the
      tedanolides.
AB  - In a synthetic approach to the completely protected C1-C12 fragment of the
      macrocyclic cytotoxic agent tedanolide 1, we carried out the tin-catalyzed
      Mukaiyama aldol reaction between the 2,3-dialkoxypropanal 5 and the silyl enol
      ether 6 derived from the ketone 7, which gave, unexpectedly, the anti aldol
      isomer, rather than the expected syn isomer 4, as the major diastereomer formed.

PMID- 18067311
TI  - Switchable-polarity solvents prepared with a single liquid component.
AB  - Known liquids that can reversibly switch their polarity at atmospheric pressure
      are all prepared as mixtures of two liquid components; we now report a series of
      switchable-polarity solvents that consist, in their low-polarity form, of only a
      single liquid component, a secondary amine. These solvents operate in a polarity
      range that is significantly lower than those of previously reported switchable
      solvents. Application to the separation and purification of a polymer and
      recovery of a catalyst is described.

PMID- 18067312
TI  - Density functional theory guided design of exo-selective dehydroalanine
      dienophiles for application toward the synthesis of palau'amine.
AB  - Diels-Alder cycloadditions of dehydroalanine derivatives with cyclopentadiene,
      applicable to the synthesis of palau'amine, were investigated experimentally and
      using DFT computations at the B3LYP/6-31G* level of theory. Oxazolone and
      thiohydantoin dienophiles were found to be significantly more reactive than
      hydantoins or dehydroalanine methyl esters. The increased reactivity of the
      thiohydantoins relative to hydantoins is attributed to increased conjugation of
      nitrogen lone pairs into the thiocarbonyl group. beta-Substitution greatly
      decelerates the cycloadditions due to steric interactions in the transition
      states outweighing any electronic activation by chlorine. Hydantoins and
      thiohydantoins were found to be exo-selective, while the corresponding oxazolones
      and dehydroalanines were unselective.

PMID- 18067313
TI  - A total synthesis of OSW-1.
AB  - A new and practical method was developed to synthesize OSW-1, a natural saponin
      with potent antitumor activities, from (+)-dehydroisoandrosterone, l-arabinose,
      and D-xylose on gram scale. The synthesis was achieved in 10 linear steps with an
      overall yield of 6.4% starting from (+)-dehydroisoandrosterone.

PMID- 18067314
TI  - Halo- and azidodediazoniation of arenediazonium tetrafluoroborates with
      trimethylsilyl halides and trimethylsilyl azide and sandmeyer-type
      bromodediazoniation with Cu(I)Br in [BMIM][PF6] ionic liquid.
AB  - Reaction of [ArN(2)][BF(4)] salts immobilized in [BMIM][PF(6)] ionic liquid (IL)
      with TMSX (X = I, Br) and TMSN(3) represents an efficient method for the
      preparation of iodo-, bromo-, and azido-derivatives via dediazoniation. The
      reactions can also be effected starting with ArNH(2) by in situ diazotization
      with [NO][BF(4)] followed by reaction with TMSX or TMSN(3). Depending on the
      substituents on the benzenediazonium cation, competing fluorodediazoniation (ArF
      formation) and hydrodediazoniation (ArH formation) were observed. Dediazoniation
      with TMSN(3) and with TMSI generally gave the highest chemoselectivity toward
      ArN(3) and ArI formation. The IL was recycled and reused up to 5 times with no
      appreciable decrease in the conversions. Multinuclear NMR monitoring of the
      interaction of [ArN(2)][BF(4)]/TMSX, [BMIM][PF6]/TMSX, and
      [BMIM][PF(6)]/TMSX/[ArN(2)][BF(4)] indicated that TMSF is formed primarily via
      [ArN(2)][BF(4)]/TMSX, generating [ArN(2)][X] in situ, which gives ArX on
      dediazoniation. Competing formation of ArF in Sandmeyer-type bromodediazoniation
      of [ArN(2)][BF(4)] with Cu(I)Br immobilized in the IL points to significant
      involvement of heterolytic dediazoniation.

PMID- 18067315
TI  - One step conversion of heteroaromatic-N-oxides to imidazolo-heteroarenes.
AB  - Various pyridine-, quinoline-, isoquinoline-, and pyrimidine-N-oxides were
      converted to their corresponding alpha-imidazoloheteroarenes in good yield by
      treatment with sulfuryl diimidazole in nonpolar solvents at elevated
      temperatures.

PMID- 18067316
TI  - Synthesis of indazoles by the [3+2] cycloaddition of diazo compounds with arynes
      and subsequent acyl migration.
AB  - The [3+2] cycloaddition of a variety of diazo compounds with o
      (trimethylsilyl)aryl triflates in the presence of CsF or TBAF at room temperature
      provides a very direct, efficient approach to a wide range of potentially
      biologically and pharmaceutically interesting substituted indazoles in good to
      excellent yields under mild reaction conditions. Simple diazomethane derivatives
      afford N-unsubstituted indazoles or 1-arylated indazoles, depending upon the
      stoichiometry of the reagents and the reaction conditions, while dicarbonyl
      containing diazo compounds undergo carbonyl migration to afford 1-acyl or 1
      alkoxycarbonyl indazoles selectively.

PMID- 18067317
TI  - New strategies for cyclization and bicyclization of oligonucleotides by click
      chemistry assisted by microwaves.
AB  - The synthesis of cyclic, branched, and bicyclic oligonucleotides was performed by
      copper-catalyzed azide-alkyne cycloaddition assisted by microwaves in solution
      and on solid support. For that purpose, new phosphoramidite building blocks and
      new solid supports were designed to introduce alkyne and bromo functions into the
      same oligonucleotide by solid-phase synthesis on a DNA synthesizer. The bromine
      atom was then substituted by sodium azide to yield azide oligonucleotides.
      Cyclizations were found to be more efficient in solution than on solid support.
      This method allowed the efficient preparation of cyclic (6- to 20-mers), branched
      (with one or two dangling sequences), and bicyclic (2 x 10-mers)
      oligonucleotides.

PMID- 18067318
TI  - Rapid formation and slow collapse of a carbocation-anion pair to a neutral
      molecule.
AB  - The 4,4',4' '-trimethoxytrityl cation (TMT(+)) was observed to react with acetate
      ion in acetic acid reversibly to give the corresponding ester (TMT-OAc). The rate
      of the reaction was found to be independent of [NaOAc] over a 25000-fold range.
      Similar results were observed in the presence of Bu(4)N(+) in acetic acid as well
      as in HOAc/AN (1/1). It was concluded that {TMT(+) (HOAc/AcO(-))} is an ion pair
      that forms essentially completely from free TMT(+) and HOAc/AcO(-) during the
      time of mixing under stopped-flow conditions. The process which was studied
      kinetically is the intramolecular collapse of the ion pair to TMT-OAc which takes
      place in two steps involving a kinetically significant intermediate. The
      remarkably close resemblance of this reaction to the Winstein scheme for
      solvolysis reactions is noted. In analogy to the Winstein scheme, it was proposed
      that the intermediate could be an intimate ion pair formed upon extrusion of
      solvent from the solvent separated ion pair. The product-forming step could then
      correspond to the intimate ion pair reacting further to form a covalent bond
      between the two moieties within the complex. The values of the thermodynamic and
      the activation parameters as well as the apparent rate constants for the reaction
      in the presence of either sodium or tetrabutylammonium ions suggest that these
      counterions play insignificant roles in the reactions. However, the equilibrium
      constant for the intramolecular step (K(4)) was observed to be two times greater
      in the presence of Bu(4)N(+) than in the presence of Na(+). The rate of the
      reaction in HOAc was observed to be about four times as great as that in HOAc/AN
      (1/1).

PMID- 18067319
TI  - The neuronal voltage-dependent sodium channel type II IQ motif lowers the calcium
      affinity of the C-domain of calmodulin.
AB  - Calmodulin (CaM) is the primary calcium sensor in eukaryotes. Calcium binds
      cooperatively to pairs of EF-hand motifs in each domain (N and C). This allows
      CaM to regulate cellular processes via calcium-dependent interactions with a
      variety of proteins, including ion channels. One neuronal target is NaV1.2,
      voltage-dependent sodium channel type II, to which CaM binds via an IQ motif
      within the NaV1.2 C-terminal tail (residues 1901-1938) [Mori, M., et al. (2000)
      Biochemistry 39, 1316-1323]. Here we report on the use of circular dichroism,
      fluorescein emission, and fluorescence anisotropy to study the interaction
      between CaM and NaV1.2 at varying calcium concentrations. At 1 mM MgCl2, both
      full-length CaM (CaM1-148) and a C-domain fragment (CaM76-148) exhibit tight
      (nanomolar) calcium-independent binding to the NaV1.2 IQ motif, whereas an N
      domain fragment of CaM (CaM1-80) binds weakly, regardless of calcium
      concentration. Equilibrium calcium titrations of CaM at several concentrations of
      the NaV1.2 IQ peptide showed that the peptide reduced the calcium affinity of the
      CaM C-domain sites (III and IV) without affecting the N-domain sites (I and II)
      significantly. This leads us to propose that the CaM C-domain mediates
      constitutive binding to the NaV1.2 peptide, but that interaction then distorts
      calcium-binding sites III and IV, thereby reducing their affinity for calcium.
      This contrasts with the CaM-binding domains of voltage-dependent Ca2+ channels,
      kinases, and phosphatases, which increase the calcium binding affinity of the C
      domain of CaM.

PMID- 18067320
TI  - Binding of the proline-rich segment of myelin basic protein to SH3 domains:
      spectroscopic, microarray, and modeling studies of ligand conformation and
      effects of posttranslational modifications.
AB  - Myelin basic protein (MBP) is a multifunctional protein involved in maintaining
      the stability and integrity of the myelin sheath by a variety of interactions
      with membranes and with cytoskeletal and other proteins. A central segment of MBP
      is highly conserved in mammals and consists of a membrane surface-associated
      amphipathic alpha-helix, immediately followed by a proline-rich segment that we
      hypothesize is an SH3 ligand. We show by circular dichroic spectroscopy that this
      proline-rich segment forms a polyproline type II helix in vitro under
      physiological conditions and that phosphorylation at a constituent threonyl
      residue has a stabilizing effect on its conformation. Using SH3 domain
      microarrays, we observe that the unmodified recombinant murine 18.5 kDa MBP
      isoform (rmC1 component) binds the following SH3 domains: Yes1 > PSD95 >
      cortactin = PexD = Abl = Fyn = c-Src = Itk in order of decreasing affinity. A
      quasi-deiminated form of the protein (rmC8) binds the SH3 domains Yes1 > Fyn >
      cortactin = c-Src > PexD = Abl. Phosphorylation of rmC1 at 1-2 threonines within
      the proline-rich segment by mitogen-activated protein kinase in vitro has no
      effect on the binding specificity to the SH3 domains on the array. An SH3 domain
      of chicken Fyn is also demonstrated to bind to lipid membrane-associated C1,
      phosphorylated C1, and rmC8. Molecular docking simulations of the interaction of
      the putative SH3 ligand of classic MBP with the human Fyn SH3 domain indicate
      that the strength of the interaction is of the same order of magnitude as with
      calmodulin and that the molecular recognition and association is mediated by some
      weak CH...pi interactions between the ligand prolyl residues and the aromatic
      ones of the SH3 binding site. One such interaction is well-conserved and involves
      the stacking of an MBP-peptide prolyl and an SH3 domain tryptophanyl residue, as
      in most other SH3-ligand complexes. Lysyl and arginyl residues in the peptide
      canonically interact via salt bridges and cation-pi interactions with negatively
      charged and aromatic residues in the SH3 domain binding site. Posttranslational
      modifications (phosphorylation or methylation) of the ligand cause noticeable
      shifts in the conformation of the flexible peptide and its side chains but do not
      predict any major inhibition of the binding beyond somewhat less favorable
      interactions for peptides with phosphorylated seryl or threonyl residues.

PMID- 18067321
TI  - Vibrio harveyi flavin reductase--luciferase fusion protein mimics a single
      component bifunctional monooxygenase.
AB  - Vibrio harveyi luciferase and flavin reductase FRP are, together, a two-component
      monooxygenase couple. The reduced flavin mononucleotide (FMNH2) generated by FRP
      must be supplied, through either free diffusion or direct transfer, to luciferase
      as a substrate. In contrast, single-component bifunctional monooxygenases each
      contains a bound flavin cofactor and does not require any flavin addition to
      facilitate catalysis. In this study, we generated and characterized a novel
      fusion enzyme, FRP-alphabeta, in which FRP was fused to the luciferase alpha
      subunit. Both FRP and luciferase within FRP-alphabeta were catalytically active.
      Kinetic properties characteristic of a direct transfer of FMNH2 cofactor from FRP
      to luciferase in a FRP:luciferase noncovalent complex were retained by FRP
      alphabeta. At submicromolar levels, FRP-alphabeta was significantly more active
      than an equal molar mixture of FRP and luciferase in coupled bioluminescence
      without FMN addition. Importantly, FRP-alphabeta gave a higher total quantum
      output without than with exogenously added FMN. Moreover, effects of increasing
      concentrations of oxygen on light intensity were investigated using sub
      micromolar enzymes, and results indicated that the bioluminescence produced by
      FRP-alphabeta without added flavin was derived from direct transfer of reduced
      flavin whereas bioluminescence from a mixture of FRP and luciferase with or
      without exogenously added flavin relied on free-diffusing reduced flavin.
      Therefore, the overall catalytic reaction of FRP-alphabeta without any FMN
      addition closely mimics that of a single-component bifunctional monooxygenase.
      This fusion enzyme approach could be useful to other two-component monooxygenases
      in enhancing the enzyme efficiencies under conditions hindering reduced flavin
      delivery. Other potential utilities of this approach are discussed.

PMID- 18067322
TI  - Enzymatic tRNA acylation by acid and alpha-hydroxy acid analogues of amino acids.
AB  - Incorporation of unnatural amino acids with unique chemical functionalities has
      proven to be a valuable tool for expansion of the functional repertoire and
      properties of proteins as well as for structure-function analysis. Incorporation
      of alpha-hydroxy acids (primary amino group is substituted with hydroxyl) leads
      to the synthesis of proteins with peptide bonds being substituted by ester bonds.
      Practical application of this modification is limited by the necessity to prepare
      corresponding acylated tRNA by chemical synthesis. We investigated the
      possibility of enzymatic incorporation of alpha-hydroxy acid and acid analogues
      (lacking amino group) of amino acids into tRNA using aminoacyl-tRNA synthetases
      (aaRSs). We studied direct acylation of tRNAs by alpha-hydroxy acid and acid
      analogues of amino acids and corresponding chemically synthesized analogues of
      aminoacyl-adenylates. Using adenylate analogues we were able to enzymatically
      acylate tRNA with amino acid analogues which were otherwise completely inactive
      in direct aminoacylation reaction, thus bypassing the natural mechanisms ensuring
      the selectivity of tRNA aminoacylation. Our results are the first demonstration
      that the use of synthetic aminoacyl-adenylates as substrates in tRNA
      aminoacylation reaction may provide a way for incorporation of unnatural amino
      acids into tRNA, and consequently into proteins.

PMID- 18067323
TI  - Reversible sialylation: synthesis of cytidine 5'-monophospho-N-acetylneuraminic
      acid from cytidine 5'-monophosphate with alpha2,3-sialyl O-glycan-, glycolipid-,
      and macromolecule-based donors yields diverse sialylated products.
AB  - Sialyltransferases transfer sialic acid from cytidine 5'-monophospho-N
      acetylneuraminic acid (CMP-NeuAc) to an acceptor molecule. Trans-sialidases of
      parasites transfer alpha2,3-linked sialic acid from one molecule to another
      without the involvement of CMP-NeuAc. Here we report another type of sialylation,
      termed reverse sialylation, catalyzed by mammalian sialyltransferase ST3Gal-II.
      This enzyme synthesizes CMP-NeuAc by transferring NeuAc from the
      NeuAcalpha2,3Galbeta1,3GalNAcalpha unit of O-glycans, 3-sialyl globo unit of
      glycolipids, and sialylated macromolecules to 5'-CMP. CMP-NeuAc produced in situ
      is utilized by the same enzyme to sialylate other O-glycans and by other
      sialyltransferases such as ST6Gal-I and ST6GalNAc-I, forming alpha2,6-sialylated
      compounds. ST3Gal-II also catalyzed the conversion of 5'-uridine monophosphate
      (UMP) to UMP-NeuAc, which was found to be an inactive sialyl donor. Reverse
      sialylation proceeded without the need for free sialic acid, divalent metal ions,
      or energy. Direct sialylation with CMP-NeuAc as well as the formation of CMP
      NeuAc from 5'-CMP had a wide optimum range (pH 5.2-7.2 and 4.8-6.4,
      respectively), whereas the entire reaction comprising in situ production of CMP
      NeuAc and sialylation of acceptor had a sharp optimum at pH 5.6 (activity level
      50% at pH 5.2 and 6.8, 25% at pH 4.8 and 7.2). Several properties distinguish
      forward/conventional versus reverse sialylation: (i) sodium citrate inhibited
      forward sialylation but not reverse sialylation; (ii) 5'-CDP, a potent forward
      sialyltransferase inhibitor, did not inhibit the conversion of 5'-CMP to CMP
      NeuAc; and (iii) the mucin core 2 compound 3-O
      sulfoGalbeta1,4GlcNAcbeta1,6(Galbeta1,3)GalNAcalpha-O-benzyl, an efficient
      acceptor for ST3Gal-II, inhibited the conversion of 5'-CMP to CMP-NeuAc. A
      significant level of reverse sialylation activity is noted in human prostate
      cancer cell lines LNCaP and PC3. Overall, the study demonstrates that the
      sialyltransferase reaction is readily reversible in the case of ST3Gal-II and can
      be exploited for the enzymatic synthesis of diverse sialyl products.

PMID- 18067324
TI  - Kinetic characterization of the function of myosin loop 4 in the actin-myosin
      interaction.
AB  - Myosin interacts with actin during its enzymatic cycle, and actin stimulates
      myosin's ATPase activity. There are extensive interaction surfaces on both actin
      and myosin. Several surface loops of myosin play different roles in actomyosin
      interaction. However, the functional role of loop 4 in actin binding is still
      ambiguous. We explored the role of loop 4 by either mutating its conserved acidic
      group, Glu-365, to Gln (E365Q), or by replacing the entire loop with three
      glycines (DeltaAL) in a Dictyostelium discoideum myosin II motor domain (MD)
      containing a single tryptophan residue. This native tryptophan (Trp-501) is
      located in the relay loop and is sensitive to nucleotide binding and lever-arm
      movement. Fluorescence and fast kinetic measurements showed that the mutations in
      loop 4 do not alter the enzymatic steps of the ATPase cycle in the absence of
      actin. By contrast, actin binding was significantly weakened in the absence and
      presence of ADP and ATP in both mutants. Because the strength of actin-myosin
      interaction increases in the order of rigor, ADP, and ATP complex, we conclude
      that loop 4 is a functional actin-binding region that stabilizes actomyosin
      complex, particularly in weak actin-binding states.

PMID- 18067325
TI  - Characterization and importance of the dimer interface of human calcium-activated
      nucleotidase.
AB  - Human calcium-activated nucleotidase (CAN) exists as both a membrane-bound form
      in the endoplasmic reticulum and pre-Golgi intermediate membranes and as a
      secreted, soluble form. Although the wild-type human enzyme hydrolyzes ADP
      poorly, engineered soluble human proteins (SCANs) hydrolyze ADP much more
      efficiently, making them potentially useful therapeutic proteins for treatment of
      human clotting pathologies. According to the crystal structure and the recently
      identified dimeric nature of the soluble nucleotidase, the dimer interface
      contains a central core of hydrophobic residues. Previously, we demonstrated that
      the mutation of glutamic acid 130 (located in the dimer interface) to tyrosine
      increased both the tendency to form dimers and the ADPase activity. In the
      present study, we investigated the importance of the dimeric state for enzymatic
      activity and biological function in this nucleotidase by mutating isoleucine 170,
      which is located in the center of the hydrophobic core of the dimer interface.
      The results of analytical ultracentrifugation, chemical cross-linking, and
      tryptophan fluorescence analyses demonstrated that mutation of isoleucine 170 to
      either positively or negatively charged amino acids (lys or glu) disrupted the
      calcium-dependent dimerization in soluble CAN. Furthermore, these mutations
      decreased maximal ADPase activity for both the soluble and membrane-bound
      enzymes. Although not as critical as the hydrophobic interactions centered at
      isoleucine 170, the role of hydrophilic interactions in dimer formation was also
      demonstrated. Thus, mutation of aspartic acid 228 to threonine (D228T) decreased
      both the tendency to form dimers and ADPase activity, while double mutation of
      D228T/K224N largely restored the ability to form dimers and the ADPase activity,
      further indicating that the nucleotidase activity of CAN is linked to its
      quaternary structure. Since ADPase activity of the soluble form is crucial for
      its potential development as a therapeutic protein, these findings have
      implications for engineering the soluble human calcium-activated nucleotidase for
      clinical applications. In addition, future comparison of monomeric (I170K and
      I170E mutants) and dimeric (wild-type) crystal structures of SCAN will advance
      our understanding of its enzymatic mechanism and aid in engineering efforts.

PMID- 18067326
TI  - Detection of specific solvent rearrangement regions of an enzyme: NMR and ITC
      studies with aminoglycoside phosphotransferase(3')-IIIa.
AB  - This work describes differential effects of solvent in complexes of the
      aminoglycoside phosphotransferase(3')-IIIa (APH) with different aminoglycosides
      and the detection of change in solvent structure at specific sites away from
      substrates. Binding of kanamycins to APH occurs with a larger negative DeltaH in
      H2O relative to D2O (DeltaDeltaH(H2O-D2O) < 0), while the reverse is true for
      neomycins. Unusually large negative DeltaCp values were observed for binding of
      aminoglycosides to APH. DeltaCp for the APH-neomycin complex was -1.6 kcal x mol(
      1) x deg(-1). A break at 30 degrees C was observed in the APH-kanamycin complex
      yielding DeltaCp values of -0.7 kcal x mol(-1) x deg(-1) and -3.8 kcal x mol(-1)
      x deg(-1) below and above 30 degrees C, respectively. Neither the change in
      accessible surface area (DeltaASA) nor contributions from heats of ionization
      were sufficient to explain the large negative DeltaCp values. Most significantly,
      15N-1H HSQC experiments showed that temperature-dependent shifts of the backbone
      amide protons of Leu 88, Ser 91, Cys 98, and Leu143 revealed a break at 30
      degrees C only in the APH-kanamycin complex in spectra collected between 21
      degrees C and 38 degrees C. These amino acids represent solvent reorganization
      sites that experience a change in solvent structure in their immediate
      environment as structurally different ligands bind to the enzyme. These residues
      were away from the substrate binding site and distributed in three hydrophobic
      patches in APH. Overall, our results show that a large number of factors affect
      DeltaCp and binding of structurally different ligand groups cause different
      solvent structure in the active site as well as differentially affecting specific
      sites away from the ligand binding site.

PMID- 18067327
TI  - Probing the organization of photosystem II in photosynthetic membranes by atomic
      force microscopy.
AB  - Efficient photosynthetic energy transduction and its regulation depend on a
      precise supramolecular arrangement of the plant photosystem II (PSII) complex in
      grana membranes of chloroplasts. The topography of isolated photosystem II
      supercomplexes and the supramolecular organization of this complex in grana
      membrane preparations are visualized by high-resolution atomic force microscopy
      (AFM) in air in tapping mode with an active feedback control to minimize tip
      sample interactions. Systematic comparison between topographic characteristics of
      the protrusions in atomic force microscopic images and well-established high
      resolution and freeze-fracture electron microscopic data shows that the
      photosystem II organization can be properly imaged by AFM in air. Taking the
      protruding water-splitting apparatus as a topographic marker for PSII, its
      distribution and orientation in isolated grana membrane were analyzed. For the
      latter a new mathematical procedure was established, which revealed a preference
      for a parallel alignment of PSII that resembles the organization in highly
      ordered semicrystalline arrays. Furthermore, by analyzing the height of grana
      membrane stacks, we conclude that lumenal protrusions of adjacent photosystem II
      complexes in opposing membranes are displaced relative to each other. The
      functional consequences for lateral migration processes are discussed.

PMID- 18067328
TI  - Secondary alkyl hydroperoxides as inhibitors and alternate substrates for
      lipoxygenase.
AB  - Lipoxygenase plays a central role in polyunsaturated fatty acid metabolism,
      inaugurating the biosynthesis of eicosanoids in animals and phytooxylipins in
      plants. Redox cycling of the non-heme iron cofactor represents a critical element
      of the catalytic mechanism. Paradoxically, the isolated enzyme contains Fe(II),
      but the catalytically active form contains Fe(III), and the natural oxidant for
      the iron is the hydroperoxide product of the catalyzed reaction. Controlling the
      redox state of lipoxygenase iron with small molecules, inhibitors or activators,
      could be a means to modulate the activity of the enzyme. The effects of secondary
      alkyl hydroperoxides and the corresponding alcohols on soybean lipoxygenase-1
      reaction rates were investigated and found to be very different. Secondary
      alcohols were noncompetitive or linear mixed inhibitors with inhibition constants
      in the millimolar concentration range, with more hydrophobic compounds producing
      lower values. Secondary alkyl hydroperoxides were inhibitors of lipoxygenase-1
      primarily at high substrate concentration. They were more effective inhibitors
      than the alcohols, with dissociation constants in the micromolar concentration
      range. The hydroperoxides bearing longer alkyl substituents were the more
      effective inhibitors. Oxidation of the iron in lipoxygenase-1 by 2
      hydroperoxyalkanes was evident in electron paramagnetic resonance (EPR)
      measurements, but the enzyme was neither activated nor was it inactivated.
      Instead there was evidence for an entirely different reaction catalyzed by the
      enzyme, a homolytic dehydration of the hydroperoxide to produce the corresponding
      carbonyl compound.

PMID- 18067330
TI  - Profiling protein-surface interactions of multicomponent suspensions via flow
      cytometry.
AB  - This study presents the use of flow cytometry as a high-throughput quantifiable
      technique to study multicomponent adsorption interactions between proteins and
      surfaces. Flow cytometry offers the advantage of high-throughput analysis of
      multiple parameters on a very small sampling scale. This enables flow cytometry
      to distinguish between individual adsorbent particles and adsorbate components
      within a suspension. As a proof of concept study, the adsorption of three
      proteins--bovine serum albumin (BSA), bovine immunoglobulin gamma (IgG) and
      fibrinogen--onto five surface-modified organosilica microsphere surfaces was used
      as a model multicomponent system for analysis. By uniquely labeling each protein
      and solid support type with spectrally distinguishable fluorescent dyes, the
      adsorption process could be "multiplexed" allowing for simultaneous screening of
      multiple adsorbate (protein) and adsorbent (particle surface) interactions.
      Protein adsorption experiments quantified by flow cytometry were found to be
      comparable to single-component adsorption studies by solution depletion.
      Quantitative distribution of the simultaneous competitive adsorption of BSA and
      IgG indicated that, at concentrations below surface saturation, both proteins
      adsorbed onto the surface. However, at concentrations greater than surface
      saturation, BSA preferentially adsorbed. Multiplexed particle suspensions of
      optically encoded particles were modified to produce a positively and negatively
      charged surface, a grafted 3400 MW poly(ethylene glycol) layer, or a physisorbed
      BSA or IgG layer. It was observed that adsorption was rapid and irreversible on
      all of the surfaces, and preadsorbed protein layers were the most effective in
      preventing further protein adsorption.

PMID- 18067331
TI  - Contact angle hysteresis on regular pillar-like hydrophobic surfaces.
AB  - A series of pillar-like patterned silicon wafers with different pillar sizes and
      spacing are fabricated by photolithography and further modified by a self
      assembled fluorosilanated monolayer. The dynamic contact angles of water on these
      surfaces are carefully measured and found to be consistent with the theoretical
      predictions of the Cassie model and the Wenzel model. When a water drop is at the
      Wenzel state, its contact angle hysteresis increases along with an increase in
      the surface roughness. While the surface roughness is further raised beyond its
      transition roughness (from the Wenzel state to the Cassie state), the contact
      angle hysteresis (or receding contact angle) discontinuously drops (or jumps) to
      a lower (or higher) value. When a water drop is at the Cassie state, its contact
      angle hysteresis strongly depends on the solid fraction and has nothing to do
      with the surface roughness. Even for a superhydrophobic surface, the contact
      angle hysteresis may still exhibit a value as high as 41 degrees for the solid
      fraction of 0.563.

PMID- 18067332
TI  - Adhesion and friction force coupling of gecko setal arrays: implications for
      structured adhesive surfaces.
AB  - The extraordinary climbing ability of geckos is partially attributed to the fine
      structure of their toe pads, which contain arrays consisting of thousands of
      micrometer-sized stalks (setae) that are in turn terminated by millions of
      fingerlike pads (spatulae) having nanoscale dimensions. Using a surface forces
      apparatus (SFA), we have investigated the dynamic sliding characteristics of
      setal arrays subjected to various loading, unloading, and shearing conditions at
      different angles. Setal arrays were glued onto silica substrates and, once
      installed into the SFA, brought toward a polymeric substrate surface and then
      sheared. Lateral shearing of the arrays was initiated along both the "gripping"
      and "releasing" directions of the setae on the foot pads. We find that the
      anisotropic microstructure of the setal arrays gives rise to quite different
      adhesive and tribological properties when sliding along these two directions,
      depending also on the angle that the setae subtend with respect to the surface.
      Thus, dragging the setal arrays along the gripping direction leads to strong
      adhesion and friction forces (as required during contact and attachment), whereas
      when shearing along the releasing direction, both forces fall to almost zero (as
      desired during rapid detachment). The results and analysis provide new insights
      into the biomechanics of adhesion and friction forces in animals, the coupling
      between these two forces, and the specialized structures that allow them to
      optimize these forces along different directions during movement. Our results
      also have practical implications and criteria for designing reversible and
      responsive adhesives and articulated robotic mechanisms.

PMID- 18067333
TI  - Osmotic pressure and structures of monodisperse ordered foam.
AB  - We present an experimental and numerical study of the osmotic pressure in
      monodisperse ordered foams as a function of the liquid fraction. The data are
      compared to previous results obtained for disordered monodisperse and
      polydisperse concentrated emulsions. Moreover, we report a quantitative
      investigation of the transition from a bubble close packing to a bcc structure as
      a function of the liquid volume fraction. These findings are discussed in the
      context of theoretical models that have been proposed in the literature.

PMID- 18067334
TI  - 3D force and displacement sensor for SFA and AFM measurements.
AB  - A new device has been designed, and a prototype built and tested, that can
      simultaneously measure the displacements and/or the components of a force in
      three orthogonal directions. The "3D sensor" consists of four or eight strain
      gauges attached to the four arms of a single cross-shaped force-measuring
      cantilever spring. Finite element modeling (FEM) was performed to optimize the
      design configuration to give desired sensitivity of force, displacement,
      stiffness, and resonant frequency in each direction (x, y, and z) which were
      tested on a "mesoscale" device and found to agree with the predicted values to
      within 4-10%. The device can be fitted into a surface forces apparatus (SFA), and
      a future smaller "microscale" microfabricated version can be fitted into an
      atomic force microscope (AFM) for simultaneous measurements of the normal and
      lateral (friction) forces between a tip (or colloidal bead probe) and a surface,
      and the topography of the surface. Results of the FEM analysis are presented, and
      approximate equations derived using linear elasticity theory are given for the
      sensitivity in each direction. Initial calibrations and measurements of thin film
      rheology (lubrication forces) using the "mesoscale" prototype show the device to
      function as expected.

PMID- 18067335
TI  - Molecular aspects of boundary lubrication by human lubricin: effect of disulfide
      bonds and enzymatic digestion.
AB  - Lubricin (LUB) is a glycoprotein of the synovial cavity of human articular
      joints, where it serves as an antiadhesive, boundary lubricant, and regulating
      factor for the cartilage surface. It has been proposed that these properties are
      related to the presence of a long, extended, heavily glycosylated and highly
      hydrated mucinous domain in the central part of the LUB molecule. In this work,
      we show that LUB has a contour length of 220 +/- 30 nm and a persistence length
      of < or =10 nm. LUB molecules aggregate in oligomers where the protein
      extremities are linked by disulfide bonds. We have studied the effect of
      proteolytic digestion by chymotrypsin and removal of the disulfide bonds, both of
      which mainly affect the N- and C- terminals of the protein, on the adsorption,
      normal forces, friction (lubrication) forces, and wear of LUB layers adsorbed on
      smooth, negatively charged mica surfaces, where the protein naturally forms
      lubricating polymer brush-like layers. After in situ digestion, the surface
      coverage was drastically reduced, the normal forces were altered, and both the
      coefficient of friction and the wear were dramatically increased (the COF
      increased to mu = 1.1-1.9), indicating that the mucinous domain was removed from
      the surface. Removal of disulfide bonds did not change the surface coverage or
      the overall features of the normal forces; however, we find an increase in the
      friction coefficient from mu = 0.02-0.04 to mu = 0.13-1.17 in the pressure regime
      below 6 atm, which we attribute to a higher affinity of the protein terminals for
      the surface. The necessary condition for LUB to be a good lubricant is that the
      protein be adsorbed to the surface via its terminals, leaving the central mucin
      domain free to form a low-friction, surface-protecting layer. Our results suggest
      that this "end-anchoring" has to be strong enough to impart the layer a
      sufficient resistance to shear, but without excessively restricting the
      conformational freedom of the adsorbed proteins.

PMID- 18067336
TI  - Directed copolymer assembly on chemical substrate patterns: a phenomenological
      and single-chain-in-mean-field simulations study of the influence of roughness in
      the substrate pattern.
AB  - The directed assembly of lamella-forming copolymer systems on substrates
      chemically patterned with rough stripes has been studied using a Helfrich-type,
      phenomenological theory and Single-Chain-in-Mean-Field (SCMF) simulations. The
      stripe period matches that of the lamellar spacing in the bulk. The effect of the
      line edge roughness (LER) of the substrate pattern on the microphase-separated
      morphology was investigated considering two generic types of substrate LER with a
      single characteristic wavelength imposed on the edges of the stripes: undulation
      and peristaltic LER. In both cases, the domain interfaces are pinned to the rough
      stripe boundary at the substrate and, thus, are deformed. We study how this
      deformation decays as a function of the distance from the substrate. The simple
      theory and the SCMF simulations demonstrate that one of the basic factors
      determining the decay of the roughness transferred into the self-assembled
      morphology is the characteristic LER wavelength of the substrate pattern; i.e.,
      the distance over which the roughness propagates away from the substrate
      increases with wavelength. However, both approaches reveal that, for a
      quantitative understanding of the consequences of substrate LER, it is important
      to consider the interplay of the pattern wavelength with the other characteristic
      length scales of the system, such as the film thickness and the bulk lamellar
      spacing. For instance, in thin films, the induced deformation of the lamellar
      interface decays slower with distance from the patterned surface than in thicker
      films. It is shown that the phenomenological theory can capture many of the same
      qualitative results as the SCMF simulations for copolymer assembly on substrate
      patterns with LER, but, at the same time, is limited by an incomplete description
      of the constraints on the polymer chain conformations imposed by the substrate.

PMID- 18067337
TI  - Dynamic light scattering from non-entangled wormlike micellar solutions.
AB  - The fuzzy cylinder theory, originally proposed for conventional polymer
      solutions, was applied to wormlike micellar solutions to take into account
      effects of the intermicellar collision and hydrodynamic interaction on the self
      diffusion of wormlike micelles in solution at finite concentrations. Previously
      reported apparent hydrodynamic radius data obtained by dynamic light scattering
      for non-entangled wormlike micelles formed in aqueous solution by non-ionic
      surfactants, polyoxyethylene monoalkyl ethers C(i)E(j), were analyzed by this
      theory to estimate the persistence length q of the wormlike micelles. The results
      of q estimated were consistent with those obtained from radius of gyration data
      obtained by static light scattering.

PMID- 18067338
TI  - Photochemically induced disturbance of the alkyl chain packing in vesicular
      membranes.
AB  - In previous reports, we presented the synthesis and properties of double-tailed
      azobenzene-substituted phosphate amphiphiles (Kuiper et al. Synthesis 2003, 695
      and Kuiper et al. Langmuir 2004, 20, 1152). We also reported that an ion channel
      can be regulated by trans-cis isomerization of these amphiphiles, which were
      incorporated in the membrane (Folgering et al. Langmuir 2004, 20, 6985). In the
      present study, the effect of trans-cis isomerization of both single- and double
      tailed azobenzene-substituted amphiphiles on the aggregation and packing behavior
      has been studied. The phase transition temperature of a membrane and the thermal
      half-life times of the cis azobenzene-substituted amphiphiles in membranes have
      been measured. Furthermore, the synthesis and properties of single-tailed
      azobenzene-substituted phosphate amphiphiles are described and compared with
      those of the double-tailed analogues. The single-tailed azobenzene-substituted
      phosphates have a low solubility in water and form micelles, sheets, and
      crystals. In all cases the trans-cis isomerization leads to a disturbance of the
      chain packing. Both single- and double-tailed cis azobenzene-substituted
      phosphates lowered the main phase transition temperature of bilayer membranes.
      The effect increased when the azobenzene moiety was situated closer to the head
      group. Accordingly, the half-life times of the cis azobenzene group was shorter
      when the azobenzene group was positioned closer to the head group for both the
      single- and double-tailed amphiphiles. Interestingly, the thermal cis-trans
      isomerization of the single-tailed azobenzene-substituted phosphates was faster
      in a DOPC membrane than that for the free monomer in aqueous solution.

PMID- 18067339
TI  - Cryo-fracture TEM: direct imaging of a random mesh phase.
AB  - A novel and a simple method that allows direct imaging of viscous samples by cryo
      TEM (cryo-transmission electron microscopy) is presented. A fracture on the
      vitrified sample is created in a controlled way. In the fracture, some edges are
      thin enough to allow direct imaging in transmission mode. The method was used to
      directly image a nonionic surfactant lamellar phase where a random mesh structure
      is formed at lower temperatures (<10 degrees C). A so-called random mesh phase,
      characterized by the presence of perforated surfactant bilayers, is imaged here
      for the first time. Images from the mesh structure are compared with images from
      the classical lamellar structure formed at room temperature.

PMID- 18067340
TI  - Decoupling of exchange and persistence times in atomistic models of glass
      formers.
AB  - With molecular dynamics simulations of a fluid mixture of classical particles
      interacting with pairwise additive Weeks-Chandler-Andersen potentials, we
      consider the time series of particle displacements and thereby determine the
      distributions for local persistence times and local exchange times. These basic
      characterizations of glassy dynamics are studied over a range of supercooled
      conditions and were shown to have behaviors, most notably decoupling, similar to
      those found in kinetically constrained lattice models of structural glasses.
      Implications are noted.

PMID- 18067341
TI  - Adsorption of gold on TiC(001): Au-C interactions and charge polarization.
AB  - High-resolution photoemission and first-principles density-functional slab
      calculations were used to study the adsorption of gold on a TiC(001) surface. A
      positive shift in the binding energy of the C 1s core level is observed after the
      deposition of Au on the metal carbide surface. The results of the density
      functional calculations corroborate the formation of Au-C bonds. In general, the
      bond between Au and the TiC(001) surface exhibits very little ionic character,
      but there is a substantial polarization of electrons around Au that affects its
      chemical properties.

PMID- 18067342
TI  - An automated integration-free path-integral method based on Kleinert's
      variational perturbation theory.
AB  - Based on Kleinert's variational perturbation (KP) theory [Path Integrals in
      Quantum Mechanics, Statistics, Polymer Physics, and Financial Markets, 3rd ed.
      (World Scientific, Singapore, 2004)], we present an analytic path-integral
      approach for computing the effective centroid potential. The approach enables the
      KP theory to be applied to any realistic systems beyond the first-order
      perturbation (i.e., the original Feynman-Kleinert [Phys. Rev. A 34, 5080 (1986)]
      variational method). Accurate values are obtained for several systems in which
      exact quantum results are known. Furthermore, the computed kinetic isotope
      effects for a series of proton transfer reactions, in which the potential energy
      surfaces are evaluated by density-functional theory, are in good accordance with
      experiments. We hope that our method could be used by non-path-integral experts
      or experimentalists as a "black box" for any given system.

PMID- 18067343
TI  - Adiabatic approximation of time-dependent density matrix functional response
      theory.
AB  - Time-dependent density matrix functional theory can be formulated in terms of
      coupled-perturbed response equations, in which a coupling matrix K(omega)
      features, analogous to the well-known time-dependent density functional theory
      (TDDFT) case. An adiabatic approximation is needed to solve these equations, but
      the adiabatic approximation is much more critical since there is not a good "zero
      order" as in TDDFT, in which the virtual-occupied Kohn-Sham orbital energy
      differences serve this purpose. We discuss a simple approximation proposed
      earlier which uses only results from static calculations, called the static
      approximation (SA), and show that it is deficient, since it leads to zero
      response of the natural orbital occupation numbers. This leads to wrong behavior
      in the omega-->0 limit. An improved adiabatic approximation (AA) is formulated.
      The two-electron system affords a derivation of exact coupled-perturbed equations
      for the density matrix response, permitting analytical comparison of the
      adiabatic approximation with the exact equations. For the two-electron system
      also, the exact density matrix functional (2-matrix in terms of 1-matrix) is
      known, enabling testing of the static and adiabatic approximations unobscured by
      approximations in the functional. The two-electron HeH(+) molecule shows that at
      the equilibrium distance, SA consistently underestimates the frequency-dependent
      polarizability alpha(omega), the adiabatic TDDFT overestimates alpha(omega),
      while AA improves upon SA and, indeed, AA produces the correct alpha(0). For
      stretched HeH(+), adiabatic density matrix functional theory corrects the too low
      first excitation energy and overpolarization of adiabatic TDDFT methods and
      exhibits excellent agreement with high-quality CCSD ("exact") results over a
      large omega range.

PMID- 18067344
TI  - Linear and nonlinear optical properties of some organoxenon derivatives.
AB  - We employ a series of state-of-the-art computational techniques to study the
      effect of inserting one or more Xe atoms in HC2H and HC4H, on the linear and
      nonlinear optical (L&NLO) properties of the resulting compounds. It has been
      found that the inserted Xe has a great effect on the L&NLO properties of the
      organoxenon derivatives. We analyze the bonding in HXeC2H, and the change of the
      electronic structure, which is induced by inserting Xe, in order to rationalize
      the observed extraordinary L&NLO properties. The derivatives, which are of
      interest in this work, have been synthesized in a Xe matrix. Thus the effect of
      the local field (LF), due to the Xe environment, on the properties of HXeC2H, has
      also been computed. It has been found that the LF effect on some properties is
      significant. The calculations have been performed by employing a hierarchy of
      basis sets and the techniques MP2 and CCSD(T) for taking into account
      correlation. For the interpretation of the results we have employed the complete
      active space valence bond and CASSCF/CASPT2 methods.

PMID- 18067345
TI  - Avoiding singularity problems associated with meta-GGA (generalized gradient
      approximation) exchange and correlation functionals containing the kinetic energy
      density.
AB  - Convergence problems of meta-GGA (generalized gradient approximation) XC
      (exchange and correlation) functionals containing a self-interaction correction
      term are traced back to a singularity of the latter that occurs at critical
      points of the electron density. This is demonstrated for the bond critical point
      of equilibrium and stretched H2. A simple remedy is suggested that cures meta-XC
      functionals such as VSXC, TPSS, M05, M06, and their derivatives without extra
      cost.

PMID- 18067346
TI  - Robust nonadiabatic molecular dynamics for metals and insulators.
AB  - We present a new formulation of the correlated electron-ion dynamics (CEID)
      scheme, which systematically improves Ehrenfest dynamics by including quantum
      fluctuations around the mean-field atomic trajectories. We show that the method
      can simulate models of nonadiabatic electronic transitions and test it against
      exact integration of the time-dependent Schrodinger equation. Unlike previous
      formulations of CEID, the accuracy of this scheme depends on a single tunable
      parameter which sets the level of atomic fluctuations included. The convergence
      to the exact dynamics by increasing the tunable parameter is demonstrated for a
      model two level system. This algorithm provides a smooth description of the
      nonadiabatic electronic transitions which satisfies the kinematic constraints
      (energy and momentum conservation) and preserves quantum coherence. The
      applicability of this algorithm to more complex atomic systems is discussed.

PMID- 18067347
TI  - The X1 method for accurate and efficient prediction of heats of formation.
AB  - We propose the X1 method which combines the density functional theory method with
      a neural network (NN) correction for an accurate yet efficient prediction of
      heats of formation. It calculates the final energy by using B3LYP6-311+G(3df,2p)
      at the B3LYP6-311+G(d,p) optimized geometry to obtain the B3LYP standard heats of
      formation at 298 K with the unscaled zero-point energy and thermal corrections at
      the latter basis set. The NN parameters cover 15 elements of H, Li, Be, B, C, N,
      O, F, Na, Mg, Al, Si, P, S, and Cl. The performance of X1 is close to the Gn
      theories, giving a mean absolute deviation of 1.43 kcalmol for the G399 set of
      223 molecules up to 10 nonhydrogen atoms and 1.48 kcal/mol for the X107 set of
      393 molecules up to 32 nonhydrogen atoms.

PMID- 18067348
TI  - Interpolating moving least-squares methods for fitting potential energy surfaces:
      Improving efficiency via local approximants.
AB  - The local interpolating moving least-squares (IMLS) method for constructing
      potential energy surfaces is investigated. The method retains the advantageous
      features of the IMLS approach in that the ab initio derivatives are not required
      and high degree polynomials can be used to provide accurate fits, while at the
      same time it is much more efficient than the standard IMLS approach because the
      least-squares solutions need to be calculated only once at the data points.
      Issues related to the implementation of the local IMLS method are investigated
      and the accuracy is assessed using HOOH as a test case. It is shown that the
      local IMLS method is at the same level of accuracy as the standard IMLS method.
      In addition, the scaling of the method is found to be a power law as a function
      of number of data points N, N(-q). The results suggest that when fitting only to
      the energy values for a d-dimensional system by using a Qth degree polynomial the
      power law exponent q approximately Qd when the energy range fitted is large
      (e.g., E<100 kcalmol for HOOH), and q>Qd when the energy range fitted is smaller
      (E<30 kcalmol) and the density of data points is higher. This study demonstrates
      that the local IMLS method provides an efficient and accurate means for
      constructing potential energy surfaces.

PMID- 18067349
TI  - A modified next reaction method for simulating chemical systems with time
      dependent propensities and delays.
AB  - Chemical reaction systems with a low to moderate number of molecules are
      typically modeled as discrete jump Markov processes. These systems are oftentimes
      simulated with methods that produce statistically exact sample paths such as the
      Gillespie algorithm or the next reaction method. In this paper we make explicit
      use of the fact that the initiation times of the reactions can be represented as
      the firing times of independent, unit rate Poisson processes with internal times
      given by integrated propensity functions. Using this representation we derive a
      modified next reaction method and, in a way that achieves efficiency over
      existing approaches for exact simulation, extend it to systems with time
      dependent propensities as well as to systems with delays.

PMID- 18067350
TI  - Nonlinear scaling schemes for Lennard-Jones interactions in free energy
      calculations.
AB  - Alchemical free energy calculations provide a means for the accurate
      determination of free energies from atomistic simulations and are increasingly
      used as a tool for computational studies of protein-ligand interactions. Much
      attention has been placed on efficient ways to deal with the "endpoint
      singularity" effect that can cause simulation instabilities when changing the
      number of atoms. In this study we compare the performance of linear and several
      nonlinear transformation methods, among them separation shifted "soft core"
      scaling, for a popular test system, the hydration free energy of an amino acid
      side chain. All the nonlinear methods yield similar results if extensive sampling
      is performed, but soft core scaling provides smooth lambda curves that are best
      suited for commonly used numerical integration schemes. Additionally, results
      from a more flexible solute, hexane, will also be discussed.

PMID- 18067351
TI  - Laser induced fluorescence of Mg-phthalocyanine in He droplets: evidence for
      fluxionality of large H2 clusters at 0.38 K.
AB  - The formation of Ar and H2 clusters, having up to 900 particles in helium
      droplets, has been studied via laser induced fluorescence of attached Mg
      phthalocyanine (Mg-Pc) molecules. In the experiments, one Mg-Pc molecule in
      average was added to each He droplet either before or after the cluster species,
      and the shift of the spectrum of the Mg-Pc molecules was studied as a function of
      the cluster size. For Ar clusters, about a factor of 2 smaller matrix shift was
      observed for the late pickup of the Mg-Pc molecules as compared with the prior
      pickup, indicating that in the former case, the Mg-Pc molecules reside on the
      surface of the preformed Ar clusters. On the other hand, the spectra of the Mg-Pc
      molecules attached to H2 clusters are independent of the pickup order, which is
      consistent with Mg-Pc molecules residing near the center of the H2 clusters in
      both cases. Therefore H2 clusters remain fluxional in helium droplets at T=0.38
      K. No significant differences in the spectra were observed between the para-H2
      and ortho-H2 clusters.

PMID- 18067352
TI  - Theoretical investigation of the energies and geometries of photoexcited
      uranyl(VI) ion: a comparison between wave-function theory and density functional
      theory.
AB  - In order to assess the accuracy of wave-function and density functional theory
      (DFT) based methods for excited states of the uranyl(VI) UO2(2+) molecule
      excitation energies and geometries of states originating from excitation from the
      sigma(u), sigma(g), pi(u), and pi(g) orbitals to the nonbonding 5f(delta) and
      5f(phi) have been calculated with different methods. The investigation included
      linear-response CCSD (LR-CCSD), multiconfigurational perturbation theory
      (CASSCFCASPT2), size-extensivity corrected multireference configuration
      interaction (MRCI) and AQCC, and the DFT based methods time-dependent density
      functional theory (TD-DFT) with different functionals and the hybrid DFTMRCI
      method. Excellent agreement between all nonperturbative wave-function based
      methods was obtained. CASPT2 does not give energies in agreement with the
      nonperturbative wave-function based methods, and neither does TD-DFT, in
      particular, for the higher excitations. The CAM-B3LYP functional, which has a
      corrected asymptotic behavior, improves the accuracy especially in the higher
      region of the electronic spectrum. The hybrid DFTMRCI method performs better than
      TD-DFT, again compared to the nonperturbative wave-function based results.
      However, TD-DFT, with common functionals such as B3LYP, yields acceptable
      geometries and relaxation energies for all excited states compared to LR-CCSD.
      The structure of excited states corresponding to excitation out of the highest
      occupied sigma(u) orbital are symmetric while that arising from excitations out
      of the pi(u) orbitals have asymmetric structures. The distant oxygen atom
      acquires a radical character and likely becomes a strong proton acceptor. These
      electronic states may play an important role in photoinduced proton exchange with
      a water molecule of the aqueous environment.

PMID- 18067353
TI  - The d (3)Pi(g)-c (3)Sigma(u) (+) band system of C2.
AB  - A two-dimensional fluorescence (excitation/emission) spectrum of C2 produced in
      an acetylene discharge was used to identify and separate emission bands from the
      d (3)Pi(g)<--c (3)Sigma(u) (+) and d (3)Pi(g)<--a (3)Pi(u) excitations.
      Rotationally resolved excitation spectra of the (4<--1), (5<--1), (5<--2), and
      (7<--3) bands in the d (3)Pi(g)<--c (3)Sigma(u) (+) system of C2 were observed by
      laser-induced fluorescence spectroscopy. The molecular constants of each
      vibrational level, determined from rotational analysis, were used to calculate
      the spectroscopic constants of the c (3)Sigma(u) (+) state. The principal
      molecular constants for the c (3)Sigma(u) (+) state are B(e)=1.9319(19) cm(-1),
      alpha(e)=0.018 55(69) cm(-1), omega(e)=2061.9 cm(-1), omega(e)x(e)=14.84 cm(-1),
      and T(0)(c-a)=8662.925(3) cm(-1). We report also the first experimental
      observations of dispersed fluorescence from the d (3)Pi(g) state to the c
      (3)Sigma(u) (+) state, namely, d (3)Pi(g)(v=3)-->c (3)Sigma(u) (+)(v=0,1).

PMID- 18067354
TI  - Vibrational inelastic and charge transfer processes in H(+)+H2 system: an ab
      initio study.
AB  - State-resolved differential cross sections, total and integral cross sections,
      average vibrational energy transfer, and the relative probabilities are computed
      for the H(+)+H2 system using the newly obtained ab initio potential energy
      surfaces at the full CI/cc-pVQZ level of accuracy which allow for both the direct
      vibrational inelastic and the charge transfer processes. The quantum dynamics is
      treated within the vibrational close-coupling infinite-order-sudden approximation
      approach using the two ab initio quasidiabatic potential energy surfaces. The
      computed collision attributes for both the processes are compared with the
      available state-to-state scattering experiments at E(c.m.)=20 eV. The results are
      in overall good agreement with most of the observed scattering features such as
      rainbow positions, integral cross sections, and relative vibrational energy
      transfers. A comparison with the earlier theoretical study carried out on the
      semiempirical surfaces (diatomics in molecules) is also made to illustrate the
      reliability of the potential energy surfaces used in the present work.

PMID- 18067355
TI  - Ab initio calculations on the X (1)A(') and A (1)A(") states of HPO and Franck
      Condon simulation of the single vibronic level emission spectra of HPO and DPO.
AB  - Minimum-energy geometries and relative electronic energies of the X (1)A(') and A
      (1)A(") states of HPO have been computed employing the coupled-cluster single
      double plus perturbative triple excitations {RCCSD(T)} and/or complete-active
      space self-consistent-field (CASSCF) multireference internally contracted
      configuration interaction (MRCI) methods with basis sets of up to the augmented
      correlation-consistent polarized-valence quintuple-zeta (aug-cc-pV5Z) quality. In
      addition, RCCSD(T)/aug-cc-pVQZ and CASSCF/MRCI/aug-cc-pVQZ potential energy
      functions, anharmonic vibrational wave functions, and energies involving all
      three vibrational modes for both electronic states of HPO and DPO, and Franck
      Condon factors between the two electronic states, which allow for Duschinsky
      rotation and anharmonicity, were computed. Computed Franck-Condon factors were
      then used to simulate single vibronic level (SVL) emission spectra recently
      reported by Tackett and Clouthier [J. Chem. Phys. 117, 10604 (2002)]. Excellent
      agreement between the simulated and observed spectra was obtained for the A
      (1)A(")(1,0,0)-->X (1)A(') SVL emission of HPO and DPO, when the best estimated
      ab initio geometries of the two states, which include contributions from core
      correlation and extrapolation to the complete basis set limit, were used in the
      simulation, suggesting that the best estimated ab initio geometry of the A
      (1)A(") state of HPO, particularly the bond angle of 94.5 degrees , is more
      reliable than the available experimentally derived geometry. A discussion on the
      geometrical parameters derived from rotational constants obtained from the
      rotational analysis of a high-resolution spectrum and from Franck-Condon
      simulation of the vibrational structure of an electronic spectrum is given.

PMID- 18067356
TI  - Stabilization of flat aromatic Si6 rings analogous to benzene: ab initio
      theoretical prediction.
AB  - It is shown by ab initio calculations, based on density functional (DFT/B3LYP),
      and high level coupled-cluster [CCSD(T)] and quadratic CI [QCISD(T)] methods,
      that flat aromatic silicon structures analogous to benzene (C6H6) can be
      stabilized in the presence of lithium. The resulting planar Si6Li6 structure is
      both stable and aromatic, sharing many key characteristics with benzene. To
      facilitate possible synthesis and characterization of these species, routes of
      formation with high exothermicity are suggested and several spectral properties
      (including optical absorption, infrared, and Raman) are calculated.

PMID- 18067357
TI  - Fluorescence-detected two-dimensional electronic coherence spectroscopy by
      acousto-optic phase modulation.
AB  - Two-dimensional electronic coherence spectroscopy (ECS) is an important method to
      study the coupling between distinct optical modes of a material system. Such
      studies often involve excitation using a sequence of phased ultrashort laser
      pulses. In conventional approaches, the delays between pulse temporal envelopes
      must be precisely monitored or maintained. Here, we introduce a new experimental
      scheme for phase-selective nonlinear ECS, which combines acousto-optic phase
      modulation with ultrashort laser excitation to produce intensity modulated
      nonlinear fluorescence signals. We isolate specific nonlinear signal
      contributions by synchronous detection, with respect to appropriately constructed
      references. Our method effectively decouples the relative temporal phases from
      the pulse envelopes of a collinear train of four sequential pulses. We thus
      achieve a robust and high signal-to-noise scheme for phase-selective ECS to
      investigate the resonant nonlinear optical response of photoluminescent systems.
      We demonstrate the validity of our method using a model quantum three-level
      system-atomic Rb vapor. Moreover, we show how our measurements determine the
      resonant complex-valued third-order susceptibility.

PMID- 18067358
TI  - Large attractive depletion interactions in soft repulsive-sphere binary mixtures.
AB  - We consider binary mixtures of soft repulsive spherical particles and calculate
      the depletion interaction between two big spheres mediated by the fluid of small
      spheres, using different theoretical and simulation methods. The validity of the
      theoretical approach, a virial expansion in terms of the density of the small
      spheres, is checked against simulation results. Attention is given to the
      approach toward the hard-sphere limit and to the effect of density and
      temperature on the strength of the depletion potential. Our results indicate,
      surprisingly, that even a modest degree of softness in the pair potential
      governing the direct interactions between the particles may lead to a
      significantly more attractive total effective potential for the big spheres than
      in the hard-sphere case. This might lead to significant differences in phase
      behavior, structure, and dynamics of a binary mixture of soft repulsive spheres.
      In particular, a perturbative scheme is applied to predict the phase diagram of
      an effective system of big spheres interacting via depletion forces for a size
      ratio of small and big spheres of 0.2; this diagram includes the usual fluid
      solid transition but, in the soft-sphere case, the metastable fluid-fluid
      transition, which is probably absent in hard-sphere mixtures, is close to being
      stable with respect to direct fluid-solid coexistence. From these results, the
      interesting possibility arises that, for sufficiently soft repulsive particles,
      this phase transition could become stable. Possible implications for the phase
      behavior of real colloidal dispersions are discussed.

PMID- 18067359
TI  - The single-crystal, basal face of ice I(h) investigated with sum frequency
      generation.
AB  - Sum frequency generation spectroscopy has been used to investigate the hydrogen
      bonded region of single-crystal, hexagonal ice in the temperature range of 113
      178 K. The temperature and polarization dependences of the signal are used in
      conjunction with a recent theoretical model to suggest an interpretation of the
      bluest and reddest of the hydrogen-bonded peaks. The reddest feature is
      associated with strong hydrogen bonding; the dynamic polarizability of this
      feature is primarily parallel to the surface. It is assigned to a cooperative
      motion among the companion to the free-OH and four-coordinate oscillators
      hydrogen bonded to dangling lone-pair molecules on the surface. The bluest
      hydrogen-bonded feature is similarly assigned to a cooperative motion of the OH
      stretch of dangling lone-pair molecules and of four-coordinate molecules in the
      lower half bilayer that are hydrogen bonded to free-OH molecules. Reconstruction
      induced strain is present at as low as 113 K. These results provide a richer
      picture of the ice surface than has heretofore been possible.

PMID- 18067360
TI  - A thermodynamically consistent kinetic framework for binary nucleation.
AB  - The traditional theory for binary homogeneous nucleation follows the classical
      derivation of the nucleation rate in the supposition of a hypothetical
      constrained-equilibrium distribution in the calculation of the cluster
      evaporation rate. This model enables calculation of the nucleation rate, but
      requires evaluation of the cluster distribution and cluster properties for an
      unstable equilibrium with supersaturated vapor. An alternate derivation of the
      classical homomolecular nucleation rate eliminated the need for this nonphysical
      approximation by calculating the evaporative flux at full thermodynamic
      equilibrium. The present paper develops that approach for binary nucleation; the
      framework is readily extended to ternary nucleation. In this analysis, the
      evaporative flux is evaluated by applying mass balance at full thermodynamic
      equilibrium of the system under study. This approach eliminates both the need for
      evaluating cluster properties in an unstable constrained-equilibrium state and
      ambiguity in the normalization constant required in the nucleation-rate
      expression. Moreover, it naturally spans the entire composition range between the
      two pure monomers. The cluster fluxes derived using this new model are similar in
      form to those of classical derivations, so previously developed methods for
      evaluation of the net nucleation rate can be applied directly to the new
      formulation.

PMID- 18067361
TI  - Computing the melting point and thermodynamic stability of the orthorhombic and
      monoclinic crystalline polymorphs of the ionic liquid 1-n-butyl-3
      methylimidazolium chloride.
AB  - The melting point, enthalpy of fusion, and thermodynamic stability of two crystal
      polymorphs of the ionic liquid 1-n-butyl-3-methylimidazolium chloride are
      calculated using a thermodynamic integration-based atomistic simulation method.
      The computed melting point of the orthorhombic phase ranges from 365 to 369 K,
      depending on the classical force field used. This compares reasonably well with
      the experimental values, which range from 337 to 339 K. The computed enthalpy of
      fusion ranges from 19 to 29 kJ/mol, compared to the experimental values of 18.5
      21.5 kJ/mol. Only one of the two force fields evaluated in this work yielded a
      stable monoclinic phase, despite the fact that both give accurate liquid state
      densities. The computed melting point of the monoclinic polymorph was found to be
      373 K, which is somewhat higher than the experimental range of 318-340 K. The
      computed enthalpy of fusion was 23 kJ/mol, which is also higher than the
      experimental value of 9.3-14.5 kJ/mol. The simulations predict that the
      monoclinic form is more stable than the orthorhombic form at low temperature, in
      agreement with one set of experiments but in conflict with another. The
      difference in free energy between the two polymorphs is very small, due to the
      fact that a single trans-gauche conformational difference in an alkyl sidechain
      distinguishes the two structures. As a result, it is very difficult to construct
      simple classical force fields that are accurate enough to definitively predict
      which polymorph is most stable. A liquid phase analysis of the probability
      distribution of the dihedral angles in the alkyl chain indicates that less than
      half of the dihedral angles are in the gauche-trans configuration that is adopted
      in the orthorhombic crystal. The low melting point and glass forming tendency of
      this ionic liquid is likely due to the energy barrier for conversion of the
      remaining dihedral angles into the gauche-trans state. The simulation procedure
      used to perform the melting point calculations is an extension of the so-called
      pseudo-supercritical path sampling procedure. This study demonstrates that the
      method can be effectively applied to quite complex systems such as ionic liquids
      and that the appropriate choice of tethering potentials for a key step in the
      thermodynamic path can enable first order phase transitions to be avoided.

PMID- 18067362
TI  - Interaction of water with LiCl, LiBr, and LiI in the deeply supercooled region.
AB  - The hydration mechanism of lithium halides was studied using time-of-flight
      secondary ion mass spectrometry as a function of temperature. The lithium halides
      embedded in thin films of amorphous solid water segregate to the surface at
      temperatures higher than 135-140 K, with efficiency increasing in the order of
      LiCl, LiBr, and LiI. A monolayer of LiCl and LiI adsorbed on the surface of
      amorphous solid water tends to diffuse into the bulk at 160 K. The infrared
      absorption band revealed that the aqueous lithium-halide solutions and crystals
      are formed simultaneously at 160 K; these phenomena are explicable as a
      consequence of the evolution of supercooled liquid water. The strong surfactant
      effect is inferred to arise from hydration of a contact ion pair having
      hydrophilic (lithium) and hydrophobic (halide) moieties. Furthermore, bulk
      diffusion of lithium halides might result from the formation of a solvent
      separated ion pair in supercooled liquid water. The presence of two liquid phases
      of water with different local structures is probably responsible for the
      formation of these two hydrates, consistent with the calculated result reported
      by Jungwirth and Tobias[J. Phys. Chem. B 106, 6361 (2002)].

PMID- 18067363
TI  - Analysis of band broadening in vibrational high-resolution electron-energy-loss
      spectra of condensed methane.
AB  - High-resolution vibrational electron-energy-loss spectra of multilayer condensed
      films of methane recorded at 20 K show a strong tailing of the vibrational bands
      that clearly exceeds the instrumental resolution. At low incident electron
      energy, this tailing is remarkably less important for the dipole-allowed bending
      vibration (nu(4)) than for other bands. Also, the tailing becomes less pronounced
      with increasing size of the molecule as demonstrated by spectra of ethane and
      heptane recorded under the same conditions. Dipole coupling, rotational
      broadening, and multiple inelastic scattering have been considered as origins of
      this band broadening. While the first two effects can be excluded, multiple
      scattering involving a low-frequency phonon band provides a reasonable
      explanation as demonstrated by simulations of the spectrum of methane using a
      classical two-stream model. A lower phonon frequency in the cases of the larger
      molecules is held responsible for the better resolved vibrational signals in the
      spectra of ethane and heptane.

PMID- 18067364
TI  - Extended study of molecular dynamics simulation of homogeneous vapor-liquid
      nucleation of water.
AB  - Using the simple point charge/extended water model, we performed molecular
      dynamics simulations of homogeneous vapor-liquid nucleation at various values of
      temperature T and supersaturation S, from which the nucleation rate J, critical
      nucleus size n(*), and the cluster formation free energy DeltaG were derived. As
      well as providing lots of simulation data, the results were compared with
      theories on homogeneous nucleation, including the classical, semi
      phenomenological, and scaled models, but none of these gave a satisfactory
      explanation for our results. It was found that two main factors made the theories
      fail: (1) The average cluster structure including the nonspherical shape and the
      core structure that is not like the bulk liquid and (2) the forward rate which is
      larger than assumed by the theories by about one order of magnitude. The
      quantitative evaluation of these factors is left for future investigations.

PMID- 18067365
TI  - Photoionization of isooctane and n-octane in intense laser fields. I. Effect of
      irradiance on ionization rates.
AB  - The population of ejected electrons following multiphoton ionization of neat
      liquids isooctane and n-octane is investigated over a large range of ionizing
      irradiance I(ex). Transient absorption (TA) at 1200 nm in both neat liquids is
      measured in a 60 mum path at time delays of 0.7 and 2.5 ps following an intense
      400 nm (3.1 eV) ionizing pulse. As the irradiance of this pulse is varied over
      the range from 4 to 410 TWcm(2), the dependence of TA on I(ex) exhibits the
      periodic structure theoretically predicted for multiphoton channel openings and
      closings. At low I(ex) (<9 TWcm(2)), TA in isooctane is proportional to I(ex) (n)
      where n=3, consistent with nonresonant, near threshold ionization (liquid phase
      ionization potential=8.6 eV). At I(ex)>9 TWcm(2), n declines with increasing
      I(ex) up to I(ex)=13 TWcm(2), at which point n abruptly increases to 4. The
      pattern is repeated at I(ex)>13 TWcm(2), albeit with n declining from 4 and then
      abruptly increasing to 5 as I(ex) becomes greater than 100 TWcm(2). A similar
      trend is observed in n-octane. The dependence of the TA on I(ex) in the regions
      of channel openings and closings is compared to the nonperturbative, strong field
      approximation developed by Reiss [Phys. Rev. A 22, 1786 (1980)].

PMID- 18067367
TI  - Spin selective multiple quantum NMR for spectral simplification, determination of
      relative signs, and magnitudes of scalar couplings by spin state selection.
AB  - In the present work we demonstrate a novel method for spectral simplification and
      determination of the relative signs of the scalar couplings using a spin
      selective multiple quantum NMR experiment. A spin selective excitation of double
      quantum coherence of A and M spins in a weakly coupled three spin system of the
      type AMX, results in a doublet in the double quantum dimension whose separation
      corresponds to the sum of couplings of the active spins to the passive spin X.
      One component of the doublet has the passive spin X in mid R:alpha state while
      the other component has the passive spin X in mid R:beta state. The spin
      selective conversion of double quantum coherence to single quantum coherence does
      not disturb the spin states of the passive spin thereby providing the spin state
      selection. There will be two domains of single quantum transitions in single
      quantum dimension at the chemical shift positions of A and M spins. The mid
      R:alpha domain of A spin is a doublet because of mid R:alpha and mid R:beta
      states of M spin only, while that of mid R:beta domain is another doublet in a
      different cross section of the spectra. The scalar coupling J(AM) can be
      extracted from any of the mid R:alpha and mid R:beta domain transitions while the
      relative displacements of the two doublets between the two domains at the two
      chemical shifts provides the magnitude and sign of the scalar coupling J(AX)
      relative to the coupling J(MX). Similar result is obtained for zero quantum
      studies on AMX spin system. The proposed technique is discussed theoretically
      using product operator approach. The new spin state selective double quantum J
      resolved sequence has also been developed. The methodology is confirmed
      experimentally on a homonuclear weakly coupled three spin system and applied to
      two different heteronuclear five spin systems.

PMID- 18067366
TI  - Inelastic neutron scattering study of methyl groups rotation in some
      methylxanthines.
AB  - The three isomeric dimethylxanthines and trimethylxanthine are studied by neutron
      spectroscopy up to energy transfers of 100 meV at energy resolutions ranging from
      0.7 microeV to some meV. The loss of elastic intensity with increasing
      temperature can be modeled by quasielastic methyl rotation. The number of
      inequivalent methyl groups is in agreement with those of the room temperature
      crystal structures. Activation energies are obtained. In the case of
      theophylline, a doublet tunneling band is observed at 15.1 and 17.5 microeV. In
      theobromine, a single tunneling band at 0.3 microeV is found. Orientational
      disorder in caffeine leads to a 2.7 microeV broad distribution of tunneling bands
      around the elastic line. At the same time, broad low energy phonon spectra
      characterize an orientational glassy state with weak methyl rotational
      potentials. Librational energies of the dimethylxanthines are clearly seen in the
      phonon densities of states. Rotational potentials can be derived which explain
      consistently all observables. While their symmetry in general is threefold,
      theophylline shows a close to sixfold potential reflecting a mirror symmetry.

PMID- 18067368
TI  - Vibronic dynamics of I(2) trapped in amorphous ice: coherent following of cage
      relaxation.
AB  - Four-wave mixing measurements are carried out on I(2)-doped ice, prepared by
      quench condensing the premixed vapor at 128 K. Coherent vibrational dynamics is
      observed in two distinct ensembles. The first is ascribed to trapping in
      asymmetric polar cages in which, as in water, the valence absorption of the
      molecule is blueshifted by 3500 cm(-1), predissociation of the B state is
      complete upon the first extension of the molecular bond, and the vibrational
      frequency in the ground state (observed through coherent anti-Stokes Raman
      scattering) is reduced by 6.5%. The effect is ascribed to polarization of the
      molecule. The implied local field and the ionicity of the molecule are extracted,
      to conclude that the molecule is oxygen bonded to one water molecule on one side
      and hydrogen bonded on the other side. The second ensemble is characterized by
      the transient grating signal, which shows coherent vibrational dynamics on the B
      state. The small predissociation rate in this site suggests a symmetric cage in
      which the local electric field undergoes effective cancellation; and consistent
      with this, the extracted blueshift of the valence transition in this site
      (approximately 1500 cm(-1)) coincides with that observed in clathrate hydrates of
      iodine. Remarkably, in this site, the vibrational period of the B state packet
      coherently stretches from an initial value of 245 fs to 325 fs in the course of
      five oscillations (1.3 ps), indicative of vibrationally adiabatic following of
      the cage expansion. The dynamics is characteristic of a molecule trapped in a
      tight symmetric cage, with a soft cage coordinate that relaxes without eliciting
      elastic response. Enclathration in low-density amorphous ice is concluded.

PMID- 18067369
TI  - A density functional theory study on the binding of NO onto FePc films.
AB  - To develop an atomistic understanding of the binding of NO with iron
      phthalocyanine (FePc), the interaction between NO (an electron withdrawing gas)
      and NH3 (an electron donating gas) with an isolated FePc molecule (monomer) was
      compared with density functional theory. The simulations show that NO strongly
      chemisorbs to the Fe metal and physisorbs to all the nonmetal sites.
      Additionally, when NO physisorbs to the inner ring nitrogens, NO subsequently
      undergoes a barrierless migration to the deep chemisorption well on the Fe metal.
      Conversely, NH3 only weakly chemisorbs to the Fe metal and does not bind to any
      other sites. Projected density of states simulations and analysis of the atomic
      charges show that the binding of NO to the FePc metal results in a charge
      transfer from the Fe metal to the NO chemisorbate; the opposite effect is
      observed for the binding of NH3 to the Fe metal. Simulations of NO binding to the
      Fe metal of a monolayer FePc film and FePc trimer were also performed to show
      that intermolecular FePc-FePc interactions have a negligible effect on the FePc
      electronic structure and NO binding.

PMID- 18067370
TI  - Dynamics of analyte binding onto a metallophthalocyanine: NO/FePc.
AB  - The gas-surface reaction dynamics of NO impinging on an iron(II) phthalocyanine
      (FePc) monolayer were investigated using King and Wells sticking measurements.
      The initial sticking probability was measured as a function of both incident
      molecular beam energy (0.09-0.4 eV) and surface temperature (100-300 K). NO
      adsorption onto FePc saturates at 3% of a monolayer for all incident beam
      energies and surface temperatures, suggesting that the final chemisorption site
      is confined to the Fe metal centers. At low surface temperature and low incident
      beam energy, the initial sticking probability is 40% and decreases linearly with
      increasing beam energy and surface temperature. The results are consistent with
      the NO molecule sticking onto the FePc molecules via physisorption to the
      aromatics followed by diffusion to the Fe metal center, or precursor-mediated
      chemisorption. The adsorption mechanism of NO onto FePc was confirmed by control
      studies of NO sticking onto metal-free H2Pc, inert Au111, and reactive Al111.

PMID- 18067371
TI  - A novel method for evaluating the critical nucleus and the surface tension in
      systems with first order phase transition.
AB  - We introduce a novel method for calculating the size of the critical nucleus and
      the value of the surface tension in systems with first order phase transition.
      The method is based on classical nucleation theory, and it consists in studying
      the thermodynamics of a sphere of given radius embedded in a frozen metastable
      surrounding. The frozen configuration creates a pinning field on the surface of
      the free sphere. The pinning field forces the sphere to stay in the metastable
      phase as long as its size is smaller than the critical nucleus. We test our
      method in two first order systems, both on a two-dimensional lattice: a system
      where the parameter tuning the transition is the magnetic field, and a second
      system where the tuning parameter is the temperature. In both cases the results
      are satisfying. Unlike previous techniques, our method does not require an
      infinite volume limit to compute the surface tension, and it therefore gives
      reliable estimates even by using relatively small systems. However, our method
      cannot be used at, or close to, the critical point, i.e., at coexistence, where
      the critical nucleus becomes infinitely large.

PMID- 18067372
TI  - Hydrogen absorption in bulk BC3: a first-principles study.
AB  - We have performed first-principles calculations for H absorption, H2
      dissociation, and H diffusion in bulk BC3, a graphitelike layered structure. We
      show that in bulk BC3, H2 can dissociatively (and exothermically) absorb at low
      coverages. Several low-energy pathways have been computed for the dissociation
      process. The dissociation barriers are on the order of 0.2 eV or less. This
      presents a striking contrast to the situation in pure graphite and also on
      monolayer BC3(0001), where H2 dissociative absorption is considerably more
      difficult. Hydrogen absorption at high coverages has also been investigated; we
      find that the absorption enthalpy becomes moderately more exothermic at higher
      coverages. The calculated range of H binding energies is close to the desired
      value for reversible hydrogen storage.

PMID- 18067373
TI  - Electronic and vibrational properties of nickel sulfides from first principles.
AB  - We report the results of first-principles calculations (generalized gradient
      approximation-Perdew Wang 1991) on the electronic and vibrational properties of
      several nickel sulfides that are observed on Ni-based anodes in solid oxide fuel
      cells (SOFCs) upon exposure to H2S contaminated fuels: heazlewoodite Ni3S2,
      millerite NiS, polydymite Ni3S4, and pyrite NiS2. The optimized lattice
      parameters of these sulfides are within 1% of the values determined from x-ray
      diffraction. The electronic structure analysis indicates that all Ni-S bonds are
      strongly covalent. Furthermore, it is found that the nickel d orbitals shift
      downward in energy, whereas the sulfur p orbitals shift upward with increasing
      sulfur content; this is consistent with the decrease in conductivity and
      catalytic activity of sulfur-contaminated Ni-based electrodes (or degradation in
      SOFC performance). In addition, we systematically analyze the classifications of
      the vibrational modes at the point from the crystal symmetry and calculate the
      corresponding vibrational frequencies from the optimized lattice constants. This
      information is vital to the identification with in situ vibrational spectroscopy
      of the nickel sulfides formed on Ni-based electrodes under the conditions for
      SOFC operation. Finally, the effect of thermal expansion on frequency
      calculations for the Ni3S2 system is also briefly examined.

PMID- 18067374
TI  - Structure of SiAu16: can a silicon atom be stabilized in a gold cage?
AB  - Nanostructures of Au and Si as well as Au-Si hybrid structures are topics of
      great current interest from both scientific and technological points of view.
      Recent discovery of Au clusters having fullerene-like geometries and the
      possibility of endohedral complexes with Si atoms inside the Au cage opens new
      possibilities for designing Au-Si nanostructures. Using ab initio simulated
      annealing method we have examined the stability of Si-Au16 endohedral complex.
      Contrary to what we believed, we find that the endohedral configuration is
      metastable and the structure where Si atom binds to the exterior surface of the
      Au16 cage is the lowest energy structure. The bonding of Si to Au cluster mimics
      its behavior of that in bulk and liquid phase of Au. In addition, doping of Si in
      high concentration would cause fracture and embrittlement in gold nanostructures
      just as it does in the bulk phase. Covalent bonding between Au-Au and Au-Si is
      found to be a dominant feature in the stability of the Au-Si nanostructures. Our
      study provides insight that may be useful in fabricating hybrid Au-Si
      nanostructures for applications microelectronics, catalysis, biomedicine, and
      jewelry industry.

PMID- 18067375
TI  - Macroion adsorption: the crucial role of excluded volume and co-ions.
AB  - The adsorption of charged colloids (macroions) onto an oppositely charged planar
      substrate is investigated theoretically. Taking properly into account the finite
      size of the macroions, unusual behaviors are reported. It is found that the role
      of the co-ions (the little salt-ions carrying the same sign of charge as that of
      the substrate) is crucial in understanding the mechanisms involved in the process
      of macroion adsorption. In particular, the co-ions can accumulate near the
      substrate's surface and lead to a counterintuitive surface charge amplification.

PMID- 18067376
TI  - Rotational relaxation in simple chain models.
AB  - The rotational dynamics of chemically similar systems based on freely jointed and
      freely rotating chains are studied. The second Legendre polynomial of vectors
      along chain backbones is used to investigate the rotational dynamics at different
      length scales. In a previous study, it was demonstrated that the additional bond
      angle constraint in the freely rotating case noticeably perturbs the character of
      the translational relaxation away from that of the freely jointed system. Here,
      it is shown that differences are also apparent in the two systems' rotational
      dynamics. The relaxation of the end-to-end vector is found to display a long
      time, single-exponential tail and a stretched exponential region at intermediate
      times. The stretching exponents beta are found to be 0.75+/-0.02 for the freely
      jointed case and 0.68+/-0.02 for the freely rotating case. For both system types,
      time-packing-fraction superposition is seen to hold on the end-to-end length
      scale. In addition, for both systems, the rotational relaxation times are shown
      to be proportional to the translational relaxation times, demonstrating that the
      Debye-Stokes-Einstein law holds. The second Legendre polynomial of the bond
      vector is used to probe relaxation behavior at short length scales. For the
      freely rotating case, the end-to-end relaxation times scale differently than the
      bond relaxation times, implying that the behavior is non-Stokes-Einstein, and
      that time-packing-fraction superposition does not hold across length scales for
      this system. For the freely jointed case, end-to-end relaxation times do scale
      with bond relaxation times, and both Stokes-Einstein and time-packing-fraction
      across-length-scales superposition are obeyed.

PMID- 18067377
TI  - Effects of topology and size on statics and dynamics of complexes of
      hyperbranched polymers with linear polyelectrolytes.
AB  - Brownian dynamics simulations with explicit hydrodynamic interactions have been
      employed to study generic effects of size and topology in noncovalent (Coulombic
      driven) complexes formed by irregular-shaped hyperbranched polymers and linear
      polyelectrolytes. The behavior of the complexes was explored in detail in terms
      of static and dynamic properties, both in local and in the entire complex scale.
      The results were compared to previous studies on perfect dendrimers and other
      hyperbranched molecules where available. It was found that both molecular weight
      and structure may impart significant changes to key factors known to be
      associated with the ability of these systems to take part in relevant nanoscale
      applications.

PMID- 18067378
TI  - Stern-Volmer modeling of steady-state Forster energy transfer between dilute,
      freely diffusing membrane-bound fluorophores.
AB  - Two different metrics are used to assess Forster resonance energy transfer (FRET)
      between fluorophores in the steady state: (i) acceptor-quenching of donor
      fluorescence E (also known as transfer efficiency) and (ii) donor-excited
      acceptor fluorescence F(A) (Dex). While E is still more widely used, F(A) (Dex)
      has been gaining in popularity for practical reasons among experimentalists who
      study biomembranes. Here, for the special case of membrane-bound fluorophores, we
      present a substantial body of experimental evidence that justifies the use of
      simple Stern-Volmer expressions when modeling either FRET metric under dilute
      probe conditions. We have also discovered a dilute-regime correspondence between
      our Stern-Volmer expression for E and Wolber and Hudson's series approximation
      for steady-state Forster quenching in two dimensions (2D). This novel
      correspondence allows us to interpret each of our 2D quenching constants in terms
      of both (i) an effective Forster distance and (ii) two maximum acceptor
      concentration limits, each of which defines its own useful experimental regime.
      Taken together, our results suggest a three-step strategy toward designing more
      effective steady-state FRET experiments for the study of biomembranes.

PMID- 18067379
TI  - Coherent oscillations in ultrafast fluorescence of photoactive yellow protein.
AB  - The ultrafast photoinduced dynamics of photoactive yellow protein in aqueous
      solution were studied at room temperature by femtosecond fluorescence
      spectroscopy using an optical Kerr-gate technique. Coherent oscillations of the
      wave packet were directly observed in the two-dimensional time-energy map of
      ultrafast fluorescence with 180 fs time resolution and 5 nm spectral resolution.
      The two-dimensional map revealed that four or more oscillatory components exist
      within the broad bandwidth of the fluorescence spectrum, each of which is
      restricted in the respective narrow spectral region. Typical frequencies of the
      oscillatory modes are 50 and 120 cm(-1). In the landscape on the map, the
      oscillatory components were recognized as the ridges which were winding and
      descending with time. The amplitude of the oscillatory and winding behaviors is a
      few hundred cm(-1), which is the same order as the frequencies of the
      oscillations. The mean spectral positions of the oscillatory components in the
      two-dimensional map are well explained by considering the vibrational energies of
      intramolecular modes in the electronic ground state of the chromophore. The
      entire view of the wave packet oscillations and broadening in the electronic
      excited state, accompanied by fluorescence transitions to the vibrational
      sublevels belonging to the electronic ground state, was obtained.

PMID- 18067380
TI  - Diffusion-controlled reaction on a sink with two active sites.
AB  - We have presented an exact solution for the problem of diffusive binding to a
      spherical macromolecule with two axially symmetric active patches. A highly
      accurate approximate formula for an effective steric factor has been suggested.
      This model solution may serve as a benchmark for further studies of diffusive
      interaction in more realistic models of anisotropic reactivity.

PMID- 18067381
TI  - The influence of zwitterionic lipids on the electrostatic adsorption of macroions
      onto mixed lipid membranes.
AB  - Charged lipid membranes commonly consist of a mixture of charged and zwitterionic
      lipids. We suggest a model that characterizes the influence of the dipolar nature
      of the zwitterionic lipid species on the electrostatic adsorption of macroions
      onto mixed membranes in the fluid state. The model is based on Poisson-Boltzmann
      theory which we have modified so as to account for the dipolar character of the
      zwitterionic lipids. In addition the membrane lipids are allowed to adjust their
      lateral distribution upon macroion adsorption. We consider and compare two
      experimentally relevant scenarios: cationic macroions adsorbed onto anionic
      membranes and anionic macroions adsorbed onto cationic membranes. We show that in
      the former case the adsorption strength is slightly weakened by the presence of
      the headgroup dipoles of the zwitterionic lipids. Here, macroion-induced lipid
      demixing is more pronounced and the lipid headgroups tilt away from a cationic
      macroion upon adsorption. In contrast, for the adsorption of anionic macroions
      onto a cationic membrane the zwitterionic lipids strongly participate in the
      electrostatic interaction between membrane and macroion, thus enhancing the
      adsorption strength significantly (we predict up to 20%). Consistent with that we
      find less lateral demixing of the charged lipids and a reorientation of the
      dipoles of the zwitterionic headgroups towards the anionic macroions. Our results
      may be of importance to understand the differences in the electrostatic
      adsorption of proteins/peptides onto cellular membranes versus complex formation
      between cationic membranes and DNA.

PMID- 18067383
TI  - Dynamic stability of passive dynamic walking on an irregular surface.
AB  - Falls that occur during walking are a significant health problem. One of the
      greatest impediments to solve this problem is that there is no single obviously
      "correct" way to quantify walking stability. While many people use variability as
      a proxy for stability, measures of variability do not quantify how the locomotor
      system responds to perturbations. The purpose of this study was to determine how
      changes in walking surface variability affect changes in both locomotor
      variability and stability. We modified an irreducibly simple model of walking to
      apply random perturbations that simulated walking over an irregular surface.
      Because the model's global basin of attraction remained fixed, increasing the
      amplitude of the applied perturbations directly increased the risk of falling in
      the model. We generated ten simulations of 300 consecutive strides of walking at
      each of six perturbation amplitudes ranging from zero (i.e., a smooth continuous
      surface) up to the maximum level the model could tolerate without falling over.
      Orbital stability defines how a system responds to small (i.e., "local")
      perturbations from one cycle to the next and was quantified by calculating the
      maximum Floquet multipliers for the model. Local stability defines how a system
      responds to similar perturbations in real time and was quantified by calculating
      short-term and long-term local exponential rates of divergence for the model. As
      perturbation amplitudes increased, no changes were seen in orbital stability
      (r(2)=2.43%; p=0.280) or long-term local instability (r(2)=1.0%; p=0.441). These
      measures essentially reflected the fact that the model never actually "fell"
      during any of our simulations. Conversely, the variability of the walker's
      kinematics increased exponentially (r(2)>or=99.6%; p<0.001) and short-term local
      instability increased linearly (r(2)=88.1%; p<0.001). These measures thus
      predicted the increased risk of falling exhibited by the model. For all simulated
      conditions, the walker remained orbitally stable, while exhibiting substantial
      local instability. This was because very small initial perturbations diverged
      away from the limit cycle, while larger initial perturbations converged toward
      the limit cycle. These results provide insight into how these different proposed
      measures of walking stability are related to each other and to risk of falling.

PMID- 18067384
TI  - Computational modeling to predict mechanical function of joints: application to
      the lower leg with simulation of two cadaver studies.
AB  - Computational models of musculoskeletal joints and limbs can provide useful
      information about joint mechanics. Validated models can be used as predictive
      devices for understanding joint function and serve as clinical tools for
      predicting the outcome of surgical procedures. A new computational modeling
      approach was developed for simulating joint kinematics that are dictated by
      bone/joint anatomy, ligamentous constraints, and applied loading. Three
      dimensional computational models of the lower leg were created to illustrate the
      application of this new approach. Model development began with generating three
      dimensional surfaces of each bone from CT images and then importing into the
      three-dimensional solid modeling software SOLIDWORKS and motion simulation
      package COSMOSMOTION. Through SOLIDWORKS and COSMOSMOTION, each bone surface file
      was filled to create a solid object and positioned necessary components added,
      and simulations executed. Three-dimensional contacts were added to inhibit
      intersection of the bones during motion. Ligaments were represented as linear
      springs. Model predictions were then validated by comparison to two different
      cadaver studies, syndesmotic injury and repair and ankle inversion following
      ligament transection. The syndesmotic injury model was able to predict tibial
      rotation, fibular rotation, and anterior/posterior displacement. In the inversion
      simulation, calcaneofibular ligament extension and angles of inversion compared
      well. Some experimental data proved harder to simulate accurately, due to certain
      software limitations and lack of complete experimental data. Other parameters
      that could not be easily obtained experimentally can be predicted and analyzed by
      the computational simulations. In the syndesmotic injury study, the force
      generated in the tibionavicular and calcaneofibular ligaments reduced with the
      insertion of the staple, indicating how this repair technique changes joint
      function. After transection of the calcaneofibular ligament in the inversion
      stability study, a major increase in force was seen in several of the ligaments
      on the lateral aspect of the foot and ankle, indicating the recruitment of other
      structures to permit function after injury. Overall, the computational models
      were able to predict joint kinematics of the lower leg with particular focus on
      the ankle complex. This same approach can be taken to create models of other limb
      segments such as the elbow and wrist. Additional parameters can be calculated in
      the models that are not easily obtained experimentally such as ligament forces,
      force transmission across joints, and three-dimensional movement of all bones.
      Muscle activation can be incorporated in the model through the action of applied
      forces within the software for future studies.

PMID- 18067385
TI  - Coupled motions under compressive load in intact and ACL-deficient knees: a
      cadaveric study.
AB  - Knowledge of the coupled motions, which develop under compressive loading of the
      knee, is useful to determine which degrees of freedom should be included in the
      study of tibiofemoral contact and also to understand the role of the anterior
      cruciate ligament (ACL) in coupled motions. The objectives of this study were to
      measure the coupled motions of the intact knee and ACL-deficient knee under
      compression and to compare the coupled motions of the ACL-deficient knee with
      those of the intact knee. Ten intact cadaveric knees were tested by applying a
      1600 N compressive load and measuring coupled internal-external and varus-valgus
      rotations and anterior-posterior and medial-lateral translations at 0 deg, 15
      deg, and 30 deg of flexion. Compressive loads were applied along the functional
      axis of axial rotation, which coincides approximately with the mechanical axis of
      the tibia. The ACL was excised and the knees were tested again. In the intact
      knee, the peak coupled motions were 3.8 deg internal rotation at 0 deg flexion
      changing to -4.9 deg external rotation at 30 deg of flexion, 1.4 deg of varus
      rotation at 0 deg flexion changing to -1.9 deg valgus rotation at 30 deg of
      flexion, 1.4 mm of medial translation at 0 deg flexion increasing to 2.3 mm at 30
      deg of flexion, and 5.3 mm of anterior translation at 0 deg flexion increasing to
      10.2 mm at 30 deg of flexion. All changes in the peak coupled motions from 0 deg
      to 30 deg flexion were statistically significant (p<0.05). In ACL-deficient
      knees, there was a strong trend (marginally not significant, p=0.07) toward
      greater anterior translation (12.7 mm) than that in intact knees (8.0 mm),
      whereas coupled motions in the other degrees of freedom were comparable. Because
      the coupled motions in all four degrees of freedom in the intact knee and ACL
      deficient knee are sufficiently large to substantially affect the tibiofemoral
      contact area, all degrees of freedom should be included when either developing
      mathematical models or designing mechanical testing equipment for study of
      tibiofemoral contact. The increase in coupled anterior translation in ACL
      deficient knees indicates the important role played by the ACL in constraining
      anterior translation during compressive loading.

PMID- 18067386
TI  - Finite element modeling of the left atrium to facilitate the design of an
      endoscopic atrial retractor.
AB  - With the worldwide prevalence of cardiovascular diseases, much attention has been
      focused on simulating the characteristics of the human heart to better understand
      and treat cardiac disorders. The purpose of this study is to build a finite
      element model of the left atrium (LA) that incorporates detailed anatomical
      features and realistic material characteristics to investigate the interaction of
      heart tissue and surgical instruments. This model is used to facilitate the
      design of an endoscopically deployable atrial retractor for use in minimally
      invasive, robotically assisted mitral valve repair. Magnetic resonance imaging
      (MRI) scans of a pressurized explanted porcine heart were taken to provide a 3D
      solid model of the heart geometry, while uniaxial tensile tests of porcine left
      atrial tissue were conducted to obtain realistic material properties for
      noncontractile cardiac tissue. A finite element model of the LA was constructed
      using ANSYS Release 9.0 software and the MRI data. The Mooney-Rivlin hyperelastic
      material model was chosen to characterize the passive left atrial tissue;
      material constants were derived from tensile test data. Finite element analysis
      (FEA) models of a CardioVations Port Access retractor and a prototype endoscopic
      retractor were constructed to simulate interaction between each instrument and
      the LA. These contact simulations were used to compare the quality of retraction
      between the two instruments and to optimize the design of the prototype
      retractor. Model accuracy was verified by comparing simulated cardiac wall
      deflections to those measured by MRI. FEA simulations revealed that peak forces
      of approximately 2.85 N and 2.46 N were required to retract the LA using the Port
      Access and prototype retractors, respectively. These forces varied nonlinearly
      with retractor blade displacement. Dilation of the atrial walls and rigid body
      motion of the chamber were approximately the same for both retractors. Finite
      element analysis is shown to be an effective tool for analyzing instrument/tissue
      interactions and for designing surgical instruments. The benefits of this
      approach to medical device design are significant when compared to the
      alternatives: constructing prototypes and evaluating them via animal or clinical
      trials.

PMID- 18067387
TI  - Optimal combination of minimum degrees of freedom to be actuated in the lower
      limbs to facilitate arm-free paraplegic standing.
AB  - Arm-free paraplegic standing via functional electrical stimulation (FES) has
      drawn much attention in the biomechanical field as it might allow a paraplegic to
      stand and simultaneously use both arms to perform daily activities. However,
      current FES systems for standing require that the individual actively regulates
      balance using one or both arms, thus limiting the practical use of these systems.
      The purpose of the present study was to show that actuating only six out of 12
      degrees of freedom (12-DOFs) in the lower limbs to allow paraplegics to stand
      freely is theoretically feasible with respect to multibody stability and
      physiological torque limitations of the lower limb DOF. Specifically, the goal
      was to determine the optimal combination of the minimum DOF that can be
      realistically actuated using FES while ensuring stability and able-bodied
      kinematics during perturbed arm-free standing. The human body was represented by
      a three-dimensional dynamics model with 12-DOFs in the lower limbs. Nakamura's
      method (Nakamura, Y., and Ghodoussi, U., 1989, "Dynamics Computation of Closed
      Link Robot Mechanisms With Nonredundant and Redundant Actuators," IEEE Trans.
      Rob. Autom., 5(3), pp. 294-302) was applied to estimate the joint torques of the
      system using experimental motion data from four healthy subjects. The torques
      were estimated by applying our previous finding that only 6 (6-DOFs) out of 12
      DOFs in the lower limbs need to be actuated to facilitate stable standing.
      Furthermore, it was shown that six cases of 6-DOFs exist, which facilitate stable
      standing. In order to characterize each of these cases in terms of the torque
      generation patterns and to identify a potential optimal 6-DOF combination, the
      joint torques during perturbations in eight different directions were estimated
      for all six cases of 6-DOFs. The results suggest that the actuation of both ankle
      flexionextension, both knee flexionextension, one hip flexionextension, and one
      hip abductionadduction DOF will result in the minimum torque requirements to
      regulate balance during perturbed standing. To facilitate unsupported FES
      assisted standing, it is sufficient to actuate only 6-DOFs. An optimal
      combination of 6-DOFs exists, for which this system can generate able-bodied
      kinematics while requiring lower limb joint torques that are producible using
      contemporary FES technology. These findings suggest that FES-assisted arm-free
      standing of paraplegics is theoretically feasible, even when limited by the fact
      that muscles actuating specific DOFs are often denervated or difficult to access.

PMID- 18067388
TI  - Mechanical stimulation of tendon tissue engineered constructs: effects on
      construct stiffness, repair biomechanics, and their correlation.
AB  - The objective of this study was to determine how in vitro mechanical stimulation
      of tissue engineered constructs affects their stiffness and modulus in culture
      and tendon repair biomechanics 12 weeks after surgical implantation. Using six
      female adult New Zealand White rabbits, autogenous tissue engineered constructs
      were created by seeding mesenchymal stem cells (0.1 x 10(6) cells/ml) in collagen
      gel (2.6 mg/ml) and combining both with a collagen sponge. Employing a novel
      experimental design strategy, four constructs from each animal were mechanically
      stimulated (one 1 Hz cycle every 5 min to 2.4% peak strain for 8 h/day for 2
      weeks) while the other four remained unstretched during the 2 week culture
      period. At the end of incubation, three of the mechanically stimulated (S) and
      three of the nonstimulated (NS) constructs from each animal were assigned for in
      vitro mechanical testing while the other two autogenous constructs were implanted
      into bilateral full-thickness, full-length defects created in the central third
      of rabbit patellar tendons (PTs). No significant differences were found in the in
      vitro linear stiffnesses between the S (0.15+/-0.1 N/mm) and NS constructs
      (0.08+/-0.02 N/mm; mean+/-SD). However, in vitro mechanical stimulation
      significantly increased the structural and material properties of the repair
      tissue, including a 14% increase in maximum force (p=0.01), a 50% increase in
      linear stiffness (p=0.001), and 23-41% increases in maximum stress and modulus
      (p=0.01). The S repairs achieved 65%, 80%, 60%, and 40% of normal central PT
      maximum force, linear stiffness, maximum stress, and linear modulus,
      respectively. The results for the S constructs exceed values obtained previously
      by our group using the same animal and defect model, and to our knowledge, this
      is the first study to show the benefits of in vitro mechanical stimulation on
      tendon repair biomechanics. In addition, the linear stiffnesses for the construct
      and repair were positively correlated (r=0.56) as were their linear moduli
      (r=0.68). Such in vitro predictors of in vivo outcome hold the potential to speed
      the development of tissue engineered products by reducing the time and costs of
      in vivo studies.

PMID- 18067389
TI  - An MRI-based method to align the compressive loading axis for human cadaveric
      knees.
AB  - There is a need to align the mechanical axis of the tibia with the axis of
      loading for studies involving tibiofemoral compression to interpret results and
      to ensure repeatability of loading within and among specimens. Therefore, the
      objectives of this study were (1) to develop a magnetic resonance imaging (MRI)
      based alignment method for use with apparatuses applying tibiofemoral joint
      compression, (2) to demonstrate the usefulness of the method by aligning
      cadaveric knees in an apparatus that could apply tibiofemoral joint compression,
      and (3) to quantify the error associated with the alignment method. A four degree
      of-freedom adjustable device was constructed to allow determination and alignment
      of the mechanical axis of the tibia of cadaveric knee joints with the axis of
      loading of an apparatus applying tibiofemoral joint compression. MRI was used to
      determine the locations of bony landmarks in three dimensions defining the
      mechanical axis of the tibia relative to an initial orientation of the four
      degree-of-freedom device. Adjustment values of the device were then computed and
      applied to the device to align the mechanical axis of the tibia with the axis of
      a compressive loading apparatus. To demonstrate the usefulness of the method,
      four cadaveric knees were aligned in the compressive loading apparatus. The
      vectors describing the mechanical axis of the tibia and the loading axis of the
      apparatus before and after adjustment of the four degree-of-freedom device were
      computed for each cadaveric knee. After adjustment of the four degree-of-freedom
      device, the mechanical axis of the tibia was collinear with the loading axis of
      the apparatus for each cadaveric knee. The errors in the adjustment values
      introduced by inaccuracies in the MR images were quantified using the Monte Carlo
      technique. The precisions in the translational and rotational adjustments were
      1.20 mm and 0.90 deg respectively. The MR-based alignment method will allow
      consistent interpretation of results obtained during tibiofemoral compressive
      studies conducted using the apparatus described in this paper by providing a well
      defined loading axis. The alignment method can also be adapted for use with other
      apparatuses applying tibiofemoral compression.

PMID- 18067390
TI  - In vitro evaluation of flow divertors in an elastase-induced saccular aneurysm
      model in rabbit.
AB  - Endovascular coiling is an acceptable treatment of intracranial aneurysms, yet
      long term follow-ups suggest that endovascular coiling fails to achieve complete
      aneurysm occlusions particularly in wide-neck and giant aneurysms. Placing of a
      stentlike device across the aneurysm neck may be sufficient to occlude the
      aneurysm by promoting intra-aneurysmal thrombosis; however, conclusive evidence
      of its efficacy is still lacking. In this study, we investigate in vitro the
      efficacy of custom designed flow divertors that will be subsequently implanted in
      a large cohort of animals. The aim of this study is to provide a detailed
      database against which in vivo results can be analyzed. Six custom designed flow
      divertors were fabricated and tested in vitro. The design matrix included three
      different porosities (75%, 70%, and 65%). For each porosity, there were two
      divertors with one having a nominal pore density double than that of the other.
      To quantify efficacy, the divertors were implanted in a compliant elastomeric
      model of an elastase-induced aneurysm model in rabbit and intra-aneurysmal flow
      changes were evaluated by particle image velocimetry (PIV). PIV results indicate
      a marked reduction in intra-aneurysmal flow activity after divertor implantation
      in the innominate artery across the aneurysm neck. The mean hydrodynamic
      circulation after divertor implantation was reduced to 14% or less of the mean
      circulation in the control and the mean intra-aneurysmal kinetic energy was
      reduced to 29% or less of its value in the control. The intra-aneurysmal wall
      shear rate in this model is low and implantation of the flow divertor did not
      change the wall shear rate magnitude appreciably. This in vitro experiment
      evaluates the characteristics of local flow phenomena such as hydrodynamic
      circulation, kinetic energy, wall shear rate, perforator flow, and changes of
      these parameters as a result of implantation of stentlike flow divertors in an
      elastomeric replica of elastase-induced saccular aneurysm model in rabbit. These
      initial findings offer a database for evaluation of in vivo implantations of such
      devices in the animal model and help in further development of cerebral aneurysm
      bypass devices.

PMID- 18067391
TI  - Modeling the interaction of coils with the local blood flow after coil
      embolization of intracranial aneurysms.
AB  - Aneurysmal recanalization and coil compaction after coil embolization of
      intracranial aneurysms are seen in as many as 40% of cases. Higher packing
      density has been suggested to reduce both coil compaction and recanalization.
      Basilar bifurcation aneurysms remain a challenge due possibly to the hemodynamics
      of this specific aneurysm/parent vessel architecture, which subjects the coil
      mass at the aneurysm neck to elevated and repetitive impingement forces. In the
      present study, we propose a new modeling strategy that facilitates a better
      understanding of the complex interactions between detachable coils and the local
      blood flow. In particular, a semiheuristic porous media set of equations used to
      describe the intra-aneurysmal flow is coupled to the incompressible Navier-Stokes
      equations governing the dynamics of the flow in the involved vessels. The
      resulting system of equations is solved in a strongly coupled manner using a
      finite element formulation. Our results suggest that there is a complex
      interaction between the local hemodynamics and intra-aneurysmal flow that induces
      significant forces on the coil mass. Although higher packing densities have
      previously been advocated to reduce coil compaction, our simulations suggest that
      lower permeability of the coil mass at a given packing density could also promote
      faster intra-aneurysmal thrombosis due to increased residence times.

PMID- 18067392
TI  - In-situ deformation of the aortic valve interstitial cell nucleus under diastolic
      loading.
AB  - Within the aortic valve (AV) leaflet resides a population of interstitial cells
      (AVICs), which serve to maintain tissue structural integrity via protein
      synthesis and enzymatic degradation. AVICs are typically characterized as
      myofibroblasts, exhibit phenotypic plasticity, and may play an important role in
      valve pathophysiology. While it is known that AVICs can respond to mechanical
      stimuli in vitro, the level of in vivo AVIC deformation and its relation to local
      collagen fiber reorientation during the cardiac cycle remain unknown. In the
      present study, the deformation of AVICs was investigated using porcine AV
      glutaraldehyde fixed under 0-90 mm Hg transvalvular pressures. The resulting
      change in nuclear aspect ratio (NAR) was used as an index of overall cellular
      strain, and dependencies on spatial location and pressure loading levels
      quantified. Local collagen fiber alignment in the same valves was also quantified
      using small angle light scattering. A tissue-level finite element (FE) model of
      an AVIC embedded in the AV extracellular matrix was also used explore the
      relation between AV tissue- and cellular-level deformations. Results indicated
      large, consistent increases in AVIC NAR with transvalvular pressure (e.g., from
      mean of 1.8 at 0 mm Hg to a mean of 4.8 at 90 mm Hg), as well as pronounced layer
      specific dependencies. Associated changes in collagen fiber alignment indicated
      that little AVIC deformation occurs with the large amount of fiber straightening
      for pressures below approximately 1 mm Hg, followed by substantial increases in
      AVIC NAR from 4 mm Hg to 90 mm Hg. While the tissue-level FE model was able to
      capture the qualitative response, it also underpredicted the extent of AVIC
      deformation. This result suggested that additional micromechanical and fiber
      compaction effects occur at high pressure levels. The results of this study form
      the basis of understanding transvalvular pressure-mediated mechanotransduction
      within the native AV and first time quantitative data correlating AVIC nuclei
      deformation with AV tissue microstructure and deformation.

PMID- 18067393
TI  - Effect of hyperactivity of the lateral pterygoid muscle on the temporomandibular
      joint disk.
AB  - In this study, the effect of hyperactivity of the lateral pterygoid muscle (LPM)
      on the temporomandibular joint (TMJ) disk during prolonged clenching was examined
      with a mathematical model. Finite element models of the TMJ were constructed
      based on magnetic resonance images from two subjects with or without internal
      derangement of the TMJ. For each model, muscle forces were used as a loading
      condition for stress analysis for 10 min clenching. Furthermore, an intermittent
      increase of the LPM force with intervals of 1 min was applied. In the
      asymptomatic model, large stresses were found in the central and lateral part of
      the disk at the onset of clenching. In the retrodiscal tissue, stress relaxation
      occurred during the first 2 min of clenching. When the force of the LPM increased
      temporarily, the disk moved anteriorly and returned to its original position
      afterward. In the symptomatic model, large stresses were observed in both the
      posterior region of the disk and the retrodiscal tissue throughout clenching.
      Upon temporary increase of the LPM force, the disk was elongated anteriorly,
      which appeared to be irreversible. These results indicate that hyperactivity of
      the LPM may be involved in the progression of disk displacement.

PMID- 18067394
TI  - Assessment of factors influencing finite element vertebral model predictions.
AB  - This study aimed to establish model construction and configuration procedures for
      future vertebral finite element analysis by studying convergence, sensitivity,
      and accuracy behaviors of semiautomatically generated models and comparing the
      results with manually generated models. During a previous study, six porcine
      vertebral bodies were imaged using a microcomputed tomography scanner and tested
      in axial compression to establish their stiffness and failure strength. Finite
      element models were built using a manual meshing method. In this study, the
      experimental agreement of those models was compared with that of
      semiautomatically generated models of the same six vertebrae. Both manually and
      semiautomatically generated models were assigned gray-scale-based, element
      specific material properties. The convergence of the semiautomatically generated
      models was analyzed for the complete models along with material property and
      architecture control cases. A sensitivity study was also undertaken to test the
      reaction of the models to changes in material property values, architecture, and
      boundary conditions. In control cases, the element-specific material properties
      reduce the convergence of the models in comparison to homogeneous models.
      However, the full vertebral models showed strong convergence characteristics. The
      sensitivity study revealed a significant reaction to changes in architecture,
      boundary conditions, and load position, while the sensitivity to changes in
      material property values was proportional. The semiautomatically generated models
      produced stiffness and strength predictions of similar accuracy to the manually
      generated models with much shorter image segmentation and meshing times.
      Semiautomatic methods can provide a more rapid alternative to manual mesh
      generation techniques and produce vertebral models of similar accuracy. The
      representation of the boundary conditions, load position, and surrounding
      environment is crucial to the accurate prediction of the vertebral response. At
      present, an element size of 2x2x2 mm(3) appears sufficient since the error at
      this size is dominated by factors, such as the load position, which will not be
      improved by increasing the mesh resolution. Higher resolution meshes may be
      appropriate in the future as models are made more sophisticated and computational
      processing time is reduced.

PMID- 18067395
TI  - Robust strategies for automated AFM force curve analysis-II: adhesion-influenced
      indentation of soft, elastic materials.
AB  - In the first of this two-part discourse on the extraction of elastic properties
      from atomic force microscopy (AFM) data, a scheme for automating the analysis of
      force-distance curves was introduced and experimentally validated for the
      Hertzian (i.e., linearly elastic and noninteractive probe-sample pairs)
      indentation of soft, inhomogeneous materials. In the presence of probe-sample
      adhesive interactions, which are common especially during retraction of the rigid
      tip from soft materials, the Hertzian models are no longer adequate. A number of
      theories (e.g., Johnson-Kendall-Roberts and Derjaguin-Muller-Toporov), covering
      the full range of sample compliance relative to adhesive force and tip radius,
      are available for analysis of such data. We incorporated Pietrement and Troyon's
      approximation (2000, "General Equations Describing Elastic Indentation Depth and
      Normal Contact Stiffness Versus Load," J. Colloid Interface Sci., 226(1), pp. 166
      171) of the Maugis-Dugdale model into the automated procedure. The scheme
      developed for the processing of Hertzian data was extended to allow for adhesive
      contact by applying the Pietrement-Troyon equation. Retraction force-displacement
      data from the indentation of polyvinyl alcohol gels were processed using the
      customized software. Many of the retraction curves exhibited strong adhesive
      interactions that were absent in extension. We compared the values of Young's
      modulus extracted from the retraction data to the values obtained from the
      extension data and from macroscopic uniaxial compression tests. Application of
      adhesive contact models and the automated scheme to the retraction curves yielded
      average values of Young's modulus close to those obtained with Hertzian models
      for the extension curves. The Pietrement-Troyon equation provided a good fit to
      the data as indicated by small values of the mean-square error. The Maugis
      Dugdale theory is capable of accurately modeling adhesive contact between a rigid
      spherical indenter and a soft, elastic sample. Pietrement and Troyon's empirical
      equation greatly simplifies the theory and renders it compatible with the general
      automation strategies that we developed for Hertzian analysis. Our comprehensive
      algorithm for automated extraction of Young's moduli from AFM indentation data
      has been expanded to recognize the presence of either adhesive or Hertzian
      behavior and apply the appropriate contact model.

PMID- 18067396
TI  - Mechanical properties of stapedial tendon in human middle ear.
AB  - Measurement on mechanical properties of the stapedial tendon in human middle ear
      has not been reported in the literature. In this paper, we used the material
      testing system to conduct uniaxial tensile, stress relaxation, and failure tests
      on stapedial tendon specimens harvested from human temporal bones. The digital
      image correlation method was employed to assess the boundary effect on
      experimental data. The stress-strain relationship of the tendon obtained from
      experiments was analyzed using the hyperelastic Ogden model. The results
      presented include (1) the constitutive equation of the tendon for stretch ratio
      of 1-1.4 or stress range of 0-1.45 MPa, (2) the mean ultimate stress and stretch
      ratio of the tendon at 4.04 MPa and 1.65, respectively, and (3) the hysteresis
      and normalized stress relaxation function of the tendon. The data reported in
      this paper contribute to ear mechanics, especially for theoretical analysis of
      human ear function.

PMID- 18067397
TI  - Mechanical stimulation of tissue engineered tendon constructs: effect of scaffold
      materials.
AB  - Our group has shown that numerous factors can influence how tissue engineered
      tendon constructs respond to in vitro mechanical stimulation. Although one study
      showed that stimulating mesenchymal stem cell (MSC)-collagen sponge constructs
      significantly increased construct linear stiffness and repair biomechanics, a
      second study showed no such effect when a collagen gel replaced the sponge. While
      these results suggest that scaffold material impacts the response of MSCs to
      mechanical stimulation, a well-designed intra-animal study was needed to directly
      compare the effects of type-I collagen gel versus type-I collagen sponge in
      regulating MSC response to a mechanical stimulus. Eight constructs from each cell
      line (n=8 cell lines) were created in specially designed silicone dishes. Four
      constructs were created by seeding MSCs on a type-I bovine collagen sponge, and
      the other four were formed by seeding MSCs in a purified bovine collagen gel. In
      each dish, two cell-sponge and two cell-gel constructs from each line were then
      mechanically stimulated once every 5 min to a peak strain of 2.4%, for 8 h/day
      for 2 weeks. The other dish remained in an incubator without stimulation for 2
      weeks. After 14 days, all constructs were failed to determine mechanical
      properties. Mechanical stimulation significantly improved the linear stiffness
      (0.048+/-0.009 versus 0.015+/-0.004; mean+/-SEM (standard error of the mean )
      N/mm) and linear modulus (0.016+/-0.004 versus 0.005+/-0.001; mean+/-SEM MPa) of
      cell-sponge constructs. However, the same stimulus produced no such improvement
      in cell-gel construct properties. These results confirm that collagen sponge
      rather than collagen gel facilitates how cells respond to a mechanical stimulus
      and may be the scaffold of choice in mechanical stimulation studies to produce
      functional tissue engineered structures.

PMID- 18067398
TI  - Viscoelastic properties of ovine adipose tissue covering the gluteus muscles.
AB  - Pressure-related deep tissue injury (DTI) is a life-risking form of pressure
      ulcers threatening immobilized and neurologically impaired patients. In DTI,
      necrosis of muscle and enveloping adipose tissues occurs under intact skin, owing
      to prolonged compression by bony prominences. Modeling the process of DTI in the
      buttocks requires knowledge on viscoelastic mechanical properties of the white
      adipose tissue covering the gluteus muscles. However, this information is missing
      in the literature. Our major objectives in this study were therefore to (i)
      measure short-term (H(S)) and long-term (H(L)) aggregate moduli of adipose tissue
      covering the glutei of sheep, (ii) determine the effects of preconditioning on
      H(S) and H(L), and (iii) determine the time course of stress relaxation in terms
      of the transient aggregate modulus H(t) in nonpreconditioned (NPC) and
      preconditioned (PC) tissues. We tested 20 fresh tissue specimens (from 20 mature
      animals) in vitro: 10 specimens in confined compression for obtaining the
      complete H(t) response to a ramp-and-hold protocol (ramp rate of 300 mms), and 10
      other specimens in swift indentations for obtaining comparable short-term elastic
      moduli at higher ramp rates (2000 mms). We found that H(S) in confined
      compression were 28.9+/-14.9 kPa and 18.1+/-6.9 kPa for the NPC and PC specimens,
      respectively. The H(L) property, 10.3+/-4.2 kPa, was not affected by
      preconditioning. The transient aggregate modulus H(t) always reached the plateau
      phase (less than 10% difference between H(t) and H(L)) within 2 min, which is
      substantially shorter than the times for DTI onset reported in previous animal
      studies. The short-term elastic moduli at high indentation rates were 22.6+/-10
      kPa and 15.8+/-9.4 kPa for the NPC and PC test conditions, respectively. Given a
      Poisson's ratio of 0.495, comparison of short-term elastic moduli between the
      high and slow rate tests indicated a strong deformation-rate dependency. The most
      relevant property for modeling adipose tissue as related to DTI is found to be
      H(L), which is conveniently unaffected by preconditioning. The mechanical
      characteristics of white adipose tissue provided herein are useful for analytical
      as well as numerical models of DTI, which are essential for understanding this
      serious malady.

PMID- 18067399
TI  - A MR imaging procedure to measure tarsal bone rotations.
AB  - Magnetic resonance imaging offers unique insights into three-dimensional foot
      bone motion. Thereby, adequate devices enabling defined loading and positioning
      of the foot are needed to profit from this noninvasive procedure. Tarsal bone
      positions of three healthy subjects were repeatedly measured in a pronated and a
      supinated foot excursion under bodyweight with a newly developed MR imaging
      procedure. The quantification of the transferred motion from the loading and
      positioning device to the calcaneus and an estimation of the required degrees to
      distinguish between tarsal joint rotations were used to evaluate the
      applicability of the procedure to investigate tarsal joint motion. It was found
      that 45-70% (75-95%) of the externally applied 15 deg foot pronation (supination)
      were transferred to the calcaneus. Furthermore, the talonavicular joint showed
      the largest amount of rotation up to 20 deg eversion-inversion and abadduction,
      followed by the subtalar joint showing nearly half of that motion. Considerably
      less motion was found between the cuboid and calcaneus (about 2-6 deg) and the
      cuboid nearly did not rotate relative to the navicular (on average 1 deg). The
      estimated necessary differences between tarsal joint movements to identify
      individual kinematic behavior were in the order of 2 deg (4 deg related to the
      talonavicular joint). Since the results were in agreement with the literature, it
      is concluded that the applicability of the presented procedure to investigate
      tarsal bone mechanics is warranted. The possibility to evaluate 3D tarsal joint
      motion in combination with bone morphology (e.g., joint curvature) may provide
      new insights in the still uncertain relationship between foot function and foot
      morphology.

PMID- 18067400
TI  - The coupled motion of the femur and patella during in vivo weightbearing knee
      flexion.
AB  - The movement of the knee joint consists of a coupled motion between the
      tibiofemoral and patellofemoral articulations. This study measured the six
      degrees-of-freedom kinematics of the tibia, femur, and patella using dual
      orthogonal fluoroscopy and magnetic resonance imaging. Ten normal knees from ten
      living subjects were investigated during weightbearing flexion from full
      extension to maximum flexion. The femoral and the patellar motions were measured
      relative to the tibia. The femur externally rotated by 12.9 deg and the patella
      tilted laterally by 16.3 deg during the full range of knee flexion. Knee flexion
      was strongly correlated with patellar flexion (R(2)=0.91), posterior femoral
      translation was strongly correlated to the posterior patellar translation
      (R(2)=0.87), and internal-external rotation of the femur was correlated to
      patellar tilt (R(2)=0.73) and medial-lateral patellar translation (R(2)=0.63).
      These data quantitatively indicate a kinematic coupling between the tibia, femur,
      and patella, and provide base line information on normal knee joint kinematics
      throughout the full range of weightbearing flexion. The data also suggest that
      the kinematic coupling of tibia, femur, and patella should be considered when
      investigating patellar pathologies and when developing surgical techniques to
      treat knee joint diseases.

PMID- 18067401
TI  - Developing sustainable models of rural health care: a community development
      approach.
AB  - Globally, small rural communities frequently are demographically similar to their
      neighbours and are consistently found to have a number of problems linked to the
      international phenomenon of rural decline and urban drift. For example, it is
      widely noted that rural populations have poor health status and aging
      populations. In Australia, multiple state and national policies and programs have
      been instigated to redress this situation. Yet few rural residents would agree
      that their town is the same as an apparently similar sized one nearby or across
      the country. This article reports a project that investigated the way government
      policies, health and community services, population characteristics and local
      peculiarities combined for residents in two small rural towns in New South Wales.
      Interviews and focus groups with policy makers, health and community service
      workers and community members identified the felt, expressed, normative and
      comparative needs of residents in the case-study towns. Key findings include
      substantial variation in service provision between towns because of historical
      funding allocations, workforce composition, natural disasters and distance from
      the nearest regional centre. Health and community services were more likely to be
      provided because of available funding, rather than identified community needs.
      While some services, such as mental illness intervention and GPs, are clearly in
      demand in rural areas, in these examples, more health services were not needed.
      Rather, flexibility in the services provided and work practices, role diversity
      for health and community workers and community profiling would be more effective
      to target services. The impact of industry, employment and recreation on health
      status cannot be ignored in local development.

PMID- 18067402
TI  - Errors in death certificates in a rural area of Greece.
AB  - INTRODUCTION: A death certificate is the formal document in which a physician
      records the time, cause and circumstances under which the death of an individual
      has occurred. Morbidity and mortality statistics are mainly based on the analysis
      of these certificates, and inaccuracies in the detail may lead to biased
      estimation in several epidemiological parameters. The aim of this study was to
      examine the quality of cause of death in death certificates in a rural area of
      Greece, and to identify factors that may be associated with inaccuracies in the
      completion of these death certificates. METHODS: All death certificates archived
      in the municipality of Tritaia during the period 1999-2006 were examined.
      Statistical analysis was performed by comparing the proportions of the unpaired
      case. The state of independence among the various variables was investigated by
      considering the class of discrete graphical models. RESULTS: In total, 516 death
      certificates were examined; 5.6% (29/516) were excluded because of insufficient
      demographic data. The remaining 487 death certificates were analyzed with the
      following findings: 51.5% were for males and 48.5% females (median age 82 years,
      range 5-103 years; and 83 years, range 0-104, respectively); and 39.4% (192/487)
      were correctly completed. In 168 the mechanism of death was given; in 72 multiple
      causal sequences were given; in 22 a single/not precise cause was given; and in
      33 a single causal sequence with incorrect order was given. In all, 20.1% were
      completed by a physician of the regional health centre. Gender was not associated
      with the presence of error (p = 0.352). Errors were present in 63.8% (270/423) of
      the death certificates in deceased individuals > or =60 years and in 39.1%
      (25/64) of the death certificates in individuals < or =59 years (p<0.001). In
      19.7% of the erroneously completed death certificates, the certifier was a
      physician working in primary health care. The presence of errors in death
      certificates decreased from 74.6% in 1999 to 51.8% in 2006 (p = 0.004).
      CONCLUSIONS: Giving the mechanism instead of the cause of death was the most
      frequent type of error. A statistically significant increase in the presence of
      errors was observed as the age of the descendent increased. During these 8 years,
      there has been a statistically significant decrease in errors. However, efforts
      should be made by trainers and physicians in order to improve the accuracy of the
      information in death certificates. If this is accomplished, cause-of-death
      statistics will be more accurate and so enable better health planning.

PMID- 18067403
TI  - Cut-off values for waist circumference in rural Iraqi adults for the diagnosis of
      metabolic syndrome.
AB  - BACKGROUND: The determination of cutoff points for healthy waist circumference
      (WC) is of paramount importance for prevention, optimum management, and
      prognostication of obesity, the metabolic syndrome (MetS), type 2 diabetes
      mellitus, and coronary heart disease. The aim of this project was to establish
      the cutoff level for WC in rural Basrah in Iraq, one of the eastern Mediterranean
      and Middle East (Arab) populations. METHODS: This was a community-based, cross
      sectional survey for establishing the normal value for WC among a rural district
      population in Basrah (Abu-Al-khasib), Iraq. A stratified sampling procedure was
      used for sample selection. RESULTS: The cutoff level yielding maximum sensitivity
      and specificity for predicting the presence of multiple risk factors was 97 cm in
      men and 99 cm in women. Sensitivity and specificity using these cutoff values
      were 70% and 50%, respectively, in men and 70% and 45%, respectively, in women.
      CONCLUSION: We propose the optimal cutoff point for WC for the diagnosis of MetS
      in the Iraqi adult rural population as 99 cm in women and 97 cm in men.

PMID- 18067404
TI  - Gene therapy and cement injection for restabilization of loosened hip prostheses.
AB  - Loosening of orthopedic hip prostheses is an increasing health problem. In
      elderly patients with comorbidity,revision surgery may lead to high mortality
      rates. A less invasive surgical technique is therefore required to reduce these
      patient risks. To this end a percutaneous gene therapy approach was designed to
      destroy the periprosthetic loosening membrane, and enable refixing of the hip
      prosthesis with percutaneous bone cement injections under radiological guidance.
      In this phase 1/2 dose-escalating gene therapy clinical trial, 12 patients were
      treated. Toxicity and hip function variables were monitored up to 6 months
      posttreatment. All patients completed the study and no dose-limiting toxicity was
      observed. Improvement in walking distance, independence,and pain was demonstrated
      particularly in patients receiving 3 x 10(10) and 1 x 10(11) viral particles.
      Taken together, these data show that this gene therapy approach targeted at the
      interface membrane around a loosened hip prosthesis is a feasible treatment
      option for elderly patients for whom surgical intervention is not appropriate.

PMID- 18067405
TI  - Downregulation of CD46 during muscle differentiation: implications for gene
      transfer to human skeletal muscle using group B adenoviruses.
AB  - Adenoviral vectors that use the coxsackievirus and adenovirus receptor do not
      transduce mature muscle efficiently. Group B adenoviruses use CD46 as their cell
      attachment receptor. To evaluate the utility of vectors based on group B
      adenoviruses for gene transfer to human skeletal muscle, we assessed the
      expression of CD46 in biopsied normal skeletal muscle samples and in muscles from
      patients with Duchenne muscular dystrophy. Transcript levels of CD46 were
      extremely low in mature muscle and CD46 immunoreactivity was detected only on
      blood vessels in the muscle sections. Although myoblasts cultured from biopsied
      samples had robust cell surface CD46 expression by flow cytometry, CD46
      transcript levels were barely detectable after differentiation of the myoblasts
      into myotubes. The myotubes were also much less susceptible to infection with an
      adenoviral vector carrying the fiber of serotype 35 adenovirus (AdF35). These
      results suggest that for skeletal muscle, vectors derived from group B
      adenoviruses may not be a suitable alternative to the commonly used Ad5 vectors.

PMID- 18067406
TI  - Site-specific transgene integration in the human genome catalyzed by phiBT1 phage
      integrase.
AB  - The Streptomyces phage phiBT1 integrase catalyzes recombination between phage
      attP and bacterial attB sites (att, attachment), resulting in phage DNA
      integration into the bacterial host genome in a unidirectional manner. Multiple
      pseudo-attB and -attP sites are present serendipitously in mammalian genomes and
      can recombine with wild-type attP and attB sequences. The phiBT1 system has been
      used previously to achieve site-specific integration of murine phenylalanine
      hydroxylase cDNA into hepatocytes of mice with phenylketonuria, which led to the
      complete and permanent correction of the disease phenotypes without apparent
      toxicities. Here we report the identification of three pseudo-attP and two pseudo
      attB sites in human cells, which are located in intergenic regions of five
      different chromosomes. There are no microdeletions of human genomic sequences at
      the insertional junctions and the integrated transgenes are expressed. Human
      cells expressing phiBT1 integrase showed normal karyotypes without chromosomal
      translocations between the pseudo-attB and -attP sites. Polymerase chain reaction
      analyses were performed on genomic DNA isolated from various human cell types
      expressing phiBT1 integrase, using primers flanking the pseudo-attB and -attP
      sites from mismatched human chromosomes. No chromosomal translocation events were
      detected in normal human hepatocytes, peripheral blood mononuclear cells,
      vascular microendothelial cells, and two other transformed human cell lines,
      although one such event was observed in a human melanoma cell line. The results
      suggest that the occurrence of chromosomal translocations is human cell type
      dependent, and that the phiBT1 system for site-specific integration of transgenes
      into the human genome can be used in selected applications.

PMID- 18067407
TI  - Will current technologies enable dinosaur proteomics?

PMID- 18067409
TI  - 4th International Peptide Symposium in conjunction with the 7th Australian
      Peptide Symposium and the 2nd Asia-Pacific International Peptide Symposium.

PMID- 18067410
TI  - Proteomics: from technology development to biomarker applications.

PMID- 18067411
TI  - Phosphorylation site analysis of the anti-inflammatory and mRNA-destabilizing
      protein tristetraprolin.
AB  - Tristetraprolin (TTP) is a member of the CCCH zinc finger proteins and is an anti
      inflammatory protein. Mice deficient in TTP develop a profound inflammatory
      syndrome with erosive arthritis, autoimmunity and myeloid hyperplasia. TTP binds
      to mRNA AU-rich elements with high affinity for UUAUUUAUU nucleotides and causes
      destabilization of those mRNA molecules. TTP is phosphorylated extensively in
      vivo and is a substrate for multiple protein kinases in vitro. A number of
      approaches have been used to identify its phosphorylation sites. This article
      highlights the recent progress and different approaches utilized for the
      identification of phosphorylation sites in mammalian TTP. Important but limited
      results are obtained using traditional methods, including in vivo labeling, site
      directed mutagenesis, phosphopeptide mapping and protein sequencing. Mass
      spectrometry (MS), including MALDI/MS, MALDI/MS/MS, liquid chromatography/MS/MS,
      immobilized metal ion affinity chromatography (IMAC)/MALDI/MS/MS and
      multidimensional protein identification technology has led the way in identifying
      TTP phosphorylation sites. The combination of these approaches has identified
      multiple phosphorylation sites in mammalian TTP, some of which are predicted by
      motif scanning to be phosphorylated by several protein kinases. This information
      should provide the molecular basis for future investigation of TTP's regulatory
      functions in controlling proinflammatory cytokines.

PMID- 18067412
TI  - Identification of accessible human cancer biomarkers using ex vivo chemical
      proteomic strategies.
AB  - One promising avenue towards the development of more selective, better anticancer
      drugs lies in the targeted delivery of bioactive compounds to the tumor
      environment by means of binding molecules specific for tumor-associated
      biomarkers. Eligibility of such markers for therapeutic ideally use three
      criteria: accessibility from the bloodstream; expression at sufficient level, and
      no (or much lower) expression in normal tissues. Most current discovery
      strategies (such as biomarker searching into body fluids) provide no clue as to
      whether proteins of interest are accessible, in human tissues, to suitable high
      affinity ligands, such as systemically delivered monoclonal antibodies. To
      address this limitation, our group recently developed two methodologies based on
      chemical proteomic modifications, enabling the discovery of proteins accessible
      from the bloodstream and the extracellular space in human pathological tissues.
      In this review, we will discuss the potential benefits of these methodologies for
      the fast discovery of therapeutically valuable biomarkers.

PMID- 18067413
TI  - Circulating tumor cells: detection, molecular profiling and future prospects.
AB  - Disseminated malignancy is responsible for the vast majority of cancer-related
      deaths. During this process, circulating tumor cells (CTC) are generated, spread
      from the primary tumor, colonize distant organs and lead to overt metastatic
      disease. CTC are essential for establishing metastasis; however, they are not
      sufficient as this process is highly inefficient and most will fail to grow in
      target sites. Several CTC die during migration while others remain dormant for
      several years and very few grow into macrometastases. CTC have been well
      documented in the bloodstream of cancer patients; however, the clinical relevance
      of this detection is still the subject of controversies and their biology is
      poorly understood. Indeed, available markers fail to distinguish between
      subgroups of CTC, and several current methods lack sensitivity, specificity or
      reproducibility in CTC characterization and detection. The advent of more precise
      technologies is renewing the interest in CTC biology. We will review herein
      recent findings on CTC biology, on the role of host-tumor interactions in CTC
      shedding and implantation, available methods of CTC detection and future
      perspectives for the molecular characterization of the CTC subset(s) responsible
      for the development of metastasis. Ultimately, understanding CTC biology and host
      tumor 'complementarities' will help define metastasis-related biomarkers
      providing formidable and tailored novel therapeutic targets.

PMID- 18067414
TI  - Proteomic diagnosis of Sjogren's syndrome.
AB  - In the last few years, a growing interest has arisen in the application of
      proteomic analysis to rheumatic disease. Sjogren's syndrome is a systemic disease
      that affects exocrine glands directly, and is therefore expected to influence the
      composition of the whole human saliva and lachrymal fluid. Therefore, a rising
      number of studies have been performed in an attempt to characterize the salivary
      and lachrymal protein profiles of patients with Sjogren's syndrome by using a
      proteomic approach. This review summarizes the state of the art and the potential
      application of proteomics in the systematic search for diagnostic biomarkers in
      Sjogren's syndrome.

PMID- 18067415
TI  - Ubiquitin-proteasome system dysfunction in Parkinson's disease: current evidence
      and controversies.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder.
      Although a subject of intense research, the etiology of PD remains poorly
      understood. Over the last decade, the ubiquitin-proteasome system (UPS) has
      emerged as a compelling player in PD pathogenesis. Disruption of the UPS, which
      normally identifies and degrades intracellular proteins, is thought to promote
      the toxic accumulation of proteins detrimental to neuronal survival, thereby
      contributing to their demise. Support for this came from a broad range of
      studies, including genetics, gene profiling and post-mortem analysis, as well as
      in vitro and in vivo modeling. Notably, various cellular and animal models of PD
      based on direct disruption of UPS function reproduce the salient features of PD.
      However, several gaps remain in our current knowledge regarding the precise role
      of UPS dysfunction in the pathogenesis of the disease. Current thoughts regarding
      their relationship are reviewed here and some major unresolved questions, the
      clarification of which would considerably advance our understanding of the
      implicated role of the UPS in PD pathogenesis, are discussed.

PMID- 18067416
TI  - Kinase signaling pathways as potential targets in the treatment of Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a severe, progressive, age-associated,
      neurodegenerative disorder. Current therapies are symptomatic and not effective
      at halting or significantly slowing the disease progress. The search for
      etiologic-based therapies has focused largely on genetic findings made in
      familial forms of this disease. Mutations of five genes have been unequivocally
      linked to PD; two of these, LRRK2 and PINK1, encode kinases and as such are
      attractive tools with which to understand the disease process; furthermore,
      preliminary functional data suggests that these proteins, or the pathways in
      which they are involved, are viable therapeutic targets. Here we explore the
      current data and thoughts regarding LRRK2 and PINK1 and discuss further avenues
      of research to understand the pathologic effects of mutations at these loci and
      potential points of therapeutic intervention, such as within these kinases or in
      associated pathways such as Jun N-terminal kinase and Akt pathways.

PMID- 18067417
TI  - Proteomic analysis of Saccharomyces cerevisiae.
AB  - Nowadays, proteomics is recognized as one of the fastest growing tools in many
      areas of research. This is especially true for the study of Saccharomyces
      cerevisiae, as it is considered to be a model organism for eukaryotic cells.
      Proteomic analysis provides an insight into global protein expressions from
      identification to quantitation, from localization to function, and from
      individual to network systems. Moreover, many methods for identification and
      quantitation of proteins based on tandem mass spectrometry workflows have
      recently been developed and widely applied in S. cerevisiae. The current methods
      and issues in the proteomic analysis of S. cerevisiae are reviewed here.

PMID- 18067418
TI  - Viral proteomics: global evaluation of viruses and their interaction with the
      host.
AB  - Viruses constantly adapt to and modulate the host environment during replication
      and propagation. Both DNA and RNA viruses encode multifunctional proteins that
      interact with and modify host cell proteins. While viral genomes were the first
      complete sequences known, the corresponding proteomes are only now elucidated,
      with some surprising results. Even more daunting is the task to globally monitor
      the impact of viral infection on the proteome of the host cell and many technical
      hurdles must still be overcome in order to facilitate robust and reproducible
      measurements. Further complicating the picture is the dynamic nature of proteins,
      including post-translational modifications, enzymatic cleavage and activation or
      destruction by proteolytic events. Nevertheless, several promising studies have
      been published using high-throughput methods directly measuring protein
      abundance. Particularly, quantitative or semiquantitative mass spectrometry-based
      analysis of viral and cellular proteomes are now being used to characterize
      viruses and their host interaction. In addition, the full set of interactions
      between viral and host proteins, the interactome, is beginning to emerge, with
      often unexpected interactions that need to be carefully validated. In this
      review, we will discuss two major areas of viral proteomics: first, virion
      proteomics (such as the protein characterization of viral particles) and second,
      proteoviromics, including the viral protein interactomics and the quantitative
      analysis of host cell proteome during viral infection.

PMID- 18067419
TI  - Facial expression during emotional monologues in unilateral stroke: an analysis
      of monologue segments.
AB  - Emotional monologues of brain-damaged subjects were examined to determine whether
      interhemispheric or intrahemispheric differences exist for facial emotional
      expression. A special feature was the comparison of expressions produced during
      the initial, middle, and last segments of the monologues. Videotaped emotional
      and non-emotional monologues from the New York Emotion Battery (Borod, Welkowitz,
      & Obler, 1992) of eight right brain-damaged (RBD), eight left brain-damaged
      (LBD), and eight normal control (NC) subjects, with matching for demographics and
      lesion location, were rated. Five raters were trained to evaluate the emotional
      intensity and category accuracy of the facial expressions produced during these
      monologues. Results revealed some support for a reversed valence effect, with
      RBDs showing relatively less accurate performance during positive monologues.
      Intrahemispheric results revealed that, overall, RBDs with frontal lobe lesions
      showed the least intense facial expressions. Segment analysis found that
      individuals produced facial expressions with significantly more emotional
      intensity during the middle and last thirds of the monologues than during the
      initial third of the monologues. Findings indicate intrahemispheric as well as
      interhemispheric differences in facial emotional expression and suggest the
      utilization of the latter parts of monologues in the evaluation of emotional
      expression, which has potential clinical implications.

PMID- 18067421
TI  - Learning and memory performance of children with specific language impairment
      (SLI).
AB  - The purpose of this study was to examine learning and memory in children with
      Specific Language Impairment (SLI) as compared to 30 normally functioning
      children on the Children's Memory Scale. Results indicated that children in the
      SLI group exhibited impaired performance on the Attention/Concentration Index
      (working memory), as well as significantly lower scores on both the immediate and
      delayed auditory/verbal indices and subtests relative to the control group. In
      contrast, no between group differences emerged for the visual/non-verbal indices
      and subtests. Results demonstrated that children with SLI possess normal ability
      to process, maintain and manipulate visual/non-verbal information in working
      memory along with normal ability to store and retrieve visual/non-verbal material
      from long-term storage. These results provide support for the contention that
      children with SLI have a "diminished verbal capacity" to process, organize, and
      maintain auditory information in working memory.

PMID- 18067420
TI  - Effects of patient occupation and education variables on the choice of
      neuropsychological assessment instruments.
AB  - The current study surveyed test-usage practices of clinical neuropsychologists to
      determine whether respondents varied their assessment batteries based on specific
      patient demographic characteristics. Respondents were 747 doctorate-level
      psychologists (40% usable response rate) affiliated with Division 40 of the
      American Psychological Association, National Academy of Neuropsychology, or the
      International Neuropsychological Society. Respondents read a vignette about a
      traumatic brain injury patient and subsequently reported the instruments they
      would utilize to assess this patient's memory, attention, executive functioning,
      and ability to return to work. There were three versions of the case study, which
      varied according to the patient's occupation and level of education. Results
      revealed that the reported proportion of only 9 of 516 instruments (1.7%) varied
      across classifications, indicating that some neuropsychologists slightly modified
      their test batteries based on patients' demographic characteristics. The
      implications of these findings are discussed in relation to enhancing predictions
      of real-world outcomes based on neuropsychological test data.

PMID- 18067422
TI  - The Flynn Effect revisited.
AB  - The Flynn Effect postulates that intelligence is increasing over time. However,
      as an environment becomes optimal, a plateau occurs when general growth becomes
      largely determined by genetics. There is evidence that such a plateau is
      occurring for intelligence in countries with optimal social environments. In the
      United States, examination of adult Wechsler test scores between normings
      indicates a reduction of the FSIQ increase such that average FSIQ would plateau
      about 2024. However, the WAIS-III norming process eliminates many types of
      subjects with possible brain impairment. This probably raises the average FSIQ
      level. With an increase of only 1 FSIQ point in 16 years, a plateau in the Flynn
      Effect would have been reached in 2004.

PMID- 18067423
TI  - Probable malingering and performance on the Continuous Visual Memory Test.
AB  - A known groups design involving 54 personal injury litigants, and disability
      claimants was employed to investigate group differences on the Continuous Visual
      Memory Test (CVMT). Group status was determined by performance on symptom
      validity testing and application of the Slick et al., 1999 diagnostic criteria
      for probable Malingered Neurocognitive Dysfunction (MND). Twenty-seven subjects
      who met the Slick et al., 1999 criteria formed the Probable Malingering (PM)
      group, while 27 subjects who did not comprised the Not Malingering (NM) group.
      Subjects in the PM group performed significantly worse on all CVMT variables
      (Hits, False Alarm Errors, Total Score, and Delayed Recall) relative to subjects
      in the NM group. Cutscores for the CVMT variables were empirically derived via
      logistic regression analyses. False Alarm Errors >or= 21 Total Score < or= 72 and
      Delayed Recall <or= 3 were associated with good classification accuracy (70-74%),
      and specificity (85-93%). A CVMT Total Score <or= 69, False Alarm Errors >or= 22,
      and Delayed Recall <or= 2 were all associated with 100% positive predictive
      power. The CVMT may be a valuable adjunct to the neuropsychological test battery
      for evaluating effort of personal injury litigants and disability claimants
      undergoing forensic neuropsychological evaluations.

PMID- 18067424
TI  - What do Hooper-like tests measure?
AB  - The validity of the Hooper Visual Organization Test (VOT) has been questioned by
      different authors. A set of Hooper-like puzzle tasks and a One-Detail VOT were
      developed. The items of the latter contain only the most informative detail of
      the object to be recognized. Thirty-eight patients after first-time stroke (mean
      age: 58.2 years; range: 32-70) were given both tests and a number of other
      instruments. The two tests correlated at 0.85, and similar correlation patterns
      emerged for both of them and the Wechsler Block Design with the rest of the
      battery. Furthermore, a case-matched comparison group was drawn from archival
      data for which original VOT scores were available. These were slightly, but not
      significantly higher than the One-Detail VOT scores of the experimental group.
      The results indicate that for the test as a whole, visuosynthetic abilities are
      not relevant, but most items can be successfully solved if one detail is
      presented which contains the relevant information for object recognition. With
      this in mind, Hooper-like puzzle tasks might not be the most effective way of
      measuring the different kinds of mental operations which are relevant in that
      class of visual problems.

PMID- 18067425
TI  - Psychometric properties of the Bender Gestalt Test using Lacks' version of the
      Hutt-Briskin scoring system.
AB  - Criterion-referenced (Livingston r) and norm-referenced (Gilmer-Feldt r and
      Coefficient Alpha) techniques were used to calculate the internal consistency
      reliability of the Bender-Gestalt Test (BGT) Total Score using the 12-item Lacks
      system of scoring. Livingston's r was found to be .825 for the Lacks BGT cutoff
      score of 5. The Gilmer-Feldt and alpha coefficients for the Lacks Total Score was
      found to be .644 and .626, respectively. An item analysis showed that most of the
      BGT items (9 out of 12) were within established criteria for item difficulty,
      however, 7 items were found to be poor discriminators. The interscorer
      reliabilities based on three scorers, two scorers, and a single scorer was found
      to be .895, .852, and .740, respectively. Due to the low reliabilities and
      several inherent flaws that were identified with the Lacks scoring system, the
      authors recommend that users of the BGT consider alternative objective scoring
      systems.

PMID- 18067426
TI  - "Scatter" and the construct validity of FSIQ: comment on Fiorello et al. (2007).
AB  - Two recent articles in this journal (Fiorello et al., 2007; Hale et al., 2007)
      contended that the WISC-IV FSIQ should not be interpreted for children with
      disabilities because, when index scores are diverse, the FSIQ lacks validity and
      is an insufficient description of a child's abilities. This conclusion rested in
      large part on the authors' use of a model of intelligence that does not include a
      general ability factor, making the question of the construct validity of the FSIQ
      meaningless. The present study used simulation methodology to investigate the
      effect of index score "scatter" on the construct validity of the FSIQ. It found
      the FSIQ to be equally valid at all levels of scatter, supporting the
      interpretability of the FSIQ in populations characterized by variable index-score
      profiles.

PMID- 18067427
TI  - Measurement of recovery after traumatic brain injury: a cognitive
      neuropsychological comparison of the WAIS-R with the cognitive assessment system
      (CAS) in a single case of atypical language lateralization.
AB  - A 20-year-old preferentially left-handed male suffered an extensive right, focal,
      medial, prefrontal hematoma and contusion with associated swelling, and an
      initially undetected progressive loss of consciousness following trauma to the
      forehead. Performance on the Cognitive Assessment System (CAS) at 1 and 6 months
      after traumatic brain injury was compared with performance on the WAIS-R at 6
      months post-injury. The patient demonstrated significant residualized impairment
      on selected subtests of the CAS at 6 months post-injury (all ps < 0.05). The
      patient was also significantly impaired on the Information, Vocabulary,
      Arithmetic and Comprehension verbal subtests of the WAIS-R. The magnitude of
      these WAIS-R subtest discrepancies occurred with a low base rate (< 1%) in the
      WAIS-R standardization sample. In addition there was a significant VIQ versus PIQ
      discrepancy favouring PIQ of a magnitude occurring in less than 5% of the WAIS-R
      standardization sample. These findings could not be explained on the basis of any
      prior learning disability, poor educational opportunities, medication use,
      response bias, confabulation, or low level of general ability. The low scores on
      the verbal subtests of the WAIS-R in conjunction with the impairment on the CAS
      subtests are highly suggestive of lasting frontal-executive dysfunction in this
      patient. Incidental findings of persisting anomia, impaired processing of
      proverbs, acalculia, and fluctuating verbal attention, as well as impaired
      retrieval of verbal information in the context of intact PIQ and superior
      constructional praxis suggest some degree of bilateral representation of
      linguistic functions. The differential assessment of cognitive domains by these
      two instruments as well as theoretical concordance in the pattern of results is
      also addressed.

PMID- 18067429
TI  - PSST! Wanna buy a good new memory test-cheap?: The Test of Memory and Learning-2.

PMID- 18067432
TI  - Colorectal cancer screening education, prioritization, and self-perceived
      preparedness among primary care residents: data from a national survey.
AB  - BACKGROUND: Colorectal cancer (CRC) screening remains underutilized in the United
      States. We conducted a national survey of CRC screening education,
      prioritization, and self-perceived preparedness among resident physicians in
      Family Practice (FP), Internal Medicine (IM), and Obstetrics and Gynecology
      (OB/GYN) training programs. METHODS: Directors/administrators from 1085 FP, IM,
      and OB/GYN training programs were contacted by e-mail with a request to forward
      an invitation to participate in our Web-based CRC screening education survey to
      all residents in their program. Willing residents submitted responses in
      anonymous fashion. Data were analyzed using chi2 tests and analysis of variance
      methods. RESULTS: In total, 243 program directors/administrators forwarded our
      invitation, and 835 residents responded (384 FP, 266 IM, 177 OB/GYN, 8
      undesignated specialty). Nearly all resident responders (89%) had received CRC
      screening education, but few content delivery methods were reported. Most felt at
      least somewhat comfortable or somewhat knowledgeable with respect to advising
      patients about CRC screening (90%), currently endorsed CRC screening guidelines
      (89%), and criteria used to identify familial CRC syndromes (50%). However,
      substantially fewer respondents reported feeling very comfortable or very
      knowledgeable in these areas (45%, 23%, and 5%, respectively). Program specialty,
      level of training, and gender were the strongest indicators of self-perceived
      preparedness. CONCLUSIONS: Although based on a relatively small sample of all FP,
      IM, and OB/GYN residents, these data suggest tangible opportunities to improve
      the CRC screening curriculum in primary care residency programs.

PMID- 18067433
TI  - Colorectal cancer screening perceptions and practices: results from a national
      survey of gastroenterology, surgery and radiology trainees.
AB  - BACKGROUND: Colorectal cancer (CRC) screening in the United States is suboptimal.
      We conducted a national survey to learn about CRC screening perceptions and
      practices among trainees who perform CRC screening tests including those enrolled
      in Gastroenterology and Hepatology (GIH), General and Colorectal Surgery, and
      Diagnostic and Abdominal Radiology training programs. METHODS: Program
      directors/administrators (PDs/PAs) from 642 programs were contacted by e-mail
      with an invitation to forward our survey to trainees in their programs.
      Participating trainees then completed an anonymous, Web-based questionnaire.
      RESULTS: A total of 130/642 (20%) PDs/PAs forwarded our survey to their trainees,
      with responses received from 476 trainees (80 GIH, 261 surgery, 135 radiology).
      Colonoscopy was felt to be the best CRC screening test at reducing CRC mortality,
      with patient-related factors perceived as greater barriers than system-related
      factors. No single guideline was deemed very influential on CRC screening
      practices by most trainees. A total of 2 of 5 above-average risk patient profiles
      were not recognized by most trainees. Colonoscopy was selected as the preferred
      follow-up test for a positive CRC screening test by most trainees. However, 34%
      of respondents chose an option other than colonoscopy alone for follow-up of a
      positive fecal occult blood test. CONCLUSIONS: Based on data from this national
      survey of gastroenterology, surgery, and radiology trainees, opportunities exist
      for curricular changes that may help enhance current perceptions and practices of
      trainees who perform CRC screening tests.

PMID- 18067434
TI  - Educating physician assistants as agents in cancer control: issues and
      opportunities.
AB  - BACKGROUND: Lifestyle factors (eg, smoking, diet) and compliance with screening
      recommendations play a role in cancer risk, and emerging technologies (eg, new
      vaccines, genetic testing) hold promise for improved risk management. METHODS:
      However, optimal outcomes from cancer control efforts require better preparation
      of health professionals in risk assessment, risk communication, and implementing
      health behavioral change strategies that are vitally important to cancer control.
      RESULTS AND CONCLUSION: Although physician assistants (PAs) are substantively
      engaged in cancer-related service delivery in primary care settings, few models
      exist to facilitate integration of cancer control learning experiences into the
      curricula used in intense, fast-paced, 24- to 30-month PA training programs.

PMID- 18067435
TI  - An Internet method to assess cancer patient information needs and enhance doctor
      patient communication: a pilot study.
AB  - BACKGROUND: We previously reported that doctor-patient communication in the
      cancer context may be suboptimal. We therefore developed measures to assess
      patient communication preferences and established feasibility of an Internet
      based intervention to improve communication. METHODS: Cancer patients completed
      an Internet-based survey about communication preferences, with a summary provided
      to the physician before the consultation. Patients completed a follow-up survey
      to assess consultation content and satisfaction. RESULTS: Study procedures were
      feasible, measures exhibited strong internal consistency, and patients expressed
      satisfaction with the intervention. CONCLUSION: The Internet offers an
      opportunity to assess patient preferences and prompt physicians about individual
      patient informational needs prior to the clinical encounter.

PMID- 18067436
TI  - Working with African American women to develop a cancer literacy assessment tool.
AB  - BACKGROUND: Although African American women have a lower incidence of breast
      cancer, they suffer a 30% higher age-adjusted mortality. Lower health literacy
      levels diminish women's ability to engage in cancer prevention and detection
      activities. METHODS: We conducted a focus group with lay health workers,
      following their completion of structured literacy assessments. RESULTS: The
      women's performance established the feasibility and acceptability of
      incorporating literacy assessments. However, the findings identified perceived
      limits in existing measures and identified attributes that should be included in
      cancer-focused literacy assessments. CONCLUSIONS: A cancer-specific literacy
      assessment could assist community health workers in measuring women's functional
      cancer literacy.

PMID- 18067437
TI  - Psychosocial variables associated with husbands' adjustment three months
      following wives' diagnosis of breast cancer.
AB  - BACKGROUND: Husbands of women with breast cancer may experience adjustment
      difficulties. We examined psychosocial predictors of husbands' adjustment to
      their wives' breast cancer 3 months following diagnosis. METHODS: Women (N = 45)
      with Stage I or II breast cancer who were 3 months postdiagnosis and their
      husbands completed measures of adjustment, coping, marital adjustment, and
      quality of life. RESULTS: Multiple regression analyses showed husbands' avoidant
      coping and wives' adjustment accounted for approximately 54% of the variance in
      husbands' adjustment. CONCLUSIONS: Further research on predictors of husbands'
      adjustment following wives' diagnoses of breast cancer is needed to inform
      intervention efforts.

PMID- 18067439
TI  - Basic skills for working with smokers: a pilot test of an online course for
      medical students.
AB  - BACKGROUND: Online learning can be an excellent method for presenting clinical
      skills to address health behaviors. METHODS: Medical students pilot tested a
      skills-building course consisting of an online component and a practical
      application. RESULTS: A total of 38 students were registered, 25 (66%) completed
      the online component, and 22 (58%) completed both course components. Students
      reported they were adequately trained to administer the brief 5A intervention to
      patients who smoke and they intended to deliver the intervention routinely.
      CONCLUSIONS: Online skills-building courses can have a positive effect on
      students' knowledge and skills and can be used across health behaviors promote
      healthy lifestyles.

PMID- 18067438
TI  - Oral cancer prevention and early detection: using the PRECEDE-PROCEED framework
      to guide the training of health professional students.
AB  - BACKGROUND: Teaching cancer prevention and detection is important in health
      professional education. It is desirable to select a comprehensive framework for
      teaching oral cancer (OC) prevention and detection skills. METHODS: The PRECEDE
      PROCEED model was used to design a randomized pretest and posttest study of the
      OC prevention and detection skills of dental students (n = 104). OC knowledge,
      opinions, and competencies were evaluated. RESULTS: Second year students in the
      intervention group were more competent than those in the control group.
      CONCLUSIONS: The novel use of PRECEDE-PROCEED sets a precedent for designing a
      standardized OC curriculum for a wide range of health professional disciplines.

PMID- 18067440
TI  - Cancer knowledge and perception of skills of general practice registrars in
      Australia.
AB  - BACKGROUND: The objective was to assess cancer knowledge and perception of skills
      of general practice (GP) registrars in Australia. This will help design future
      educational resources. METHODS: We surveyed GP registrars in different Australian
      states. RESULTS: Of the registrars, 86% rated highly their ability in performing
      cervical smears. Registrars reported examining more patients with breast cancer,
      lung cancer, or melanoma than rectal cancer, cancer of mouth/tongue, or lymphoma.
      More registrars rated the quality of their training as reasonable or better in
      assisting patients to stop smoking or modify alcohol intake than in cancer
      related tasks. One third rated their teaching on management of curable/incurable
      cancer and care of the dying as poor and/or very poor, and over half had never
      examined prostate or rectal cancers. CONCLUSIONS: GP registrars generally have
      good knowledge of cancer. Their exposure to cases of cancer is low, and it is of
      concern that many have never examined common tumors in our community.

PMID- 18067441
TI  - Hepatitis B awareness, knowledge, and screening among Asian Americans.
AB  - BACKGROUND: Due to the high prevalence of hepatitis B, Asian Americans have high
      rates of liver cancer. Screening for hepatitis B leads to monitoring and
      treatment and prevent further infection through vaccination of contacts. METHODS:
      We reviewed the published literature up to 2006 on hepatitis B awareness,
      knowledge, and screening among Asian Americans. RESULTS: Many Asian Americans
      lack knowledge about hepatitis B and have not been screened. Sociodemographics,
      knowledge, beliefs, and health care variables are associated with screening.
      CONCLUSIONS: Further research and health policy changes are needed to address the
      problem of hepatitis B and liver cancer among Asian Americans.

PMID- 18067443
TI  - Serotonin modulation of moth central olfactory neurons.
AB  - In the tobacco hornworm, Manduca sexta, 5-hydroxytryptamine (5HT) acting at the
      level of the antennal lobes contributes significantly to changing the moth's
      responsiveness to olfactory stimuli. 5HT targets K(+) conductances in the cells,
      increasing the excitability of central olfactory neurons and their responsiveness
      to olfactory cues. Effects of 5HT modulation are apparent not only at the single
      cell level, but also in the activity patterns of populations of neurons that
      convey olfactory information from antennal lobes to higher centers of the brain.
      Evidence suggests that 5HT-induced changes in activity within neural circuits of
      the antennal lobes might also drive structural plasticity, providing the basis
      for longer-term changes in antennal lobe function.

PMID- 18067444
TI  - Entomological reactions to Darwin's theory in the nineteenth century.
AB  - Charles Darwin first became interested in entomology during his childhood, and
      this interest grew into a beetle-collecting obsession during his college days.
      Following the voyage of the Beagle, his focus on insects shifted from collecting
      specimens to searching for insect observations that supported his theory of
      natural selection as proposed in On the Origin of Species. Initially, Darwin
      believed that entomologists were opposed to his views. Using Darwin's
      correspondence, I show that his perception was based, in part, on three reviews,
      including one that he erroneously attributed to an entomological critic, and that
      not all entomologists were opposed to his ideas. Henry Walter Bates, discoverer
      of Batesian mimicry, voiced his support of Darwin in his papers and during
      meetings of the (now Royal) Entomological Society. In America, entomologist
      Benjamin D. Walsh wrote to Darwin in 1864, expressing his support and promising
      to counter any anti-Darwinian attack, and by 1868, Darwin was enjoying
      significant entomological support on both sides of the Atlantic. After his death
      in 1882, Darwin's supporters gained influence in Britain and the United States,
      completing entomology's shift to a Darwinian perspective.

PMID- 18067445
TI  - Advancing tissue science and engineering: a foundation for the future. A multi
      agency strategic plan.

PMID- 18067446
TI  - The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and
      psychiatric diseases.
AB  - Hyperhomocysteinemia (HHcy) is related to central nervous system diseases.
      Epidemiological studies show a positive, dose-dependent relationship between
      plasma total homocysteine (tHcy) concentration and neurodegenerative disease
      risk. tHcy is a marker of B-vitamin (folate, B(12), B(6)) status.
      Hypomethylation, caused by low B-vitamin status and HHcy, is linked to key
      pathomechanisms of dementia; B-vitamin supplementation could potentially reduce
      neurological damage. In retrospective studies, the association between tHcy and
      cognition is impressive; there is also evidence that tHcy-lowering treatment
      could be effective in primary and secondary stroke prevention. Increased tHcy and
      low serum folate occur in patients with Parkinson's disease, especially those
      receiving L-dopa. There is also an association between HHcy and multiple
      sclerosis, and between B-vitamin status and depression. Studies also confirm a
      causal role for tHcy in epilepsy, and certain anti-epileptics enhance HHcy. B
      vitamin status should be optimized by ensuring sufficient intake in patients with
      neuropsychiatric diseases. HHcy occurs commonly in the elderly and can contribute
      to age-related neurodegeneration. Treatment with folic acid, B(12) and B(6)
      lowers tHcy. For secondary and primary prevention from several neuropsychiatric
      disorders, it seems prudent to actively identify deficient subjects and ensure
      sufficient vitamin intake.

PMID- 18067447
TI  - The role of hyperhomocysteinemia as well as folate, vitamin B(6) and B(12)
      deficiencies in osteoporosis: a systematic review.
AB  - Hyperhomocysteinemia (HHCY) has been suggested as a new risk factor for
      osteoporosis. Recent epidemiological, clinical and experimental studies provide a
      growing body of data, which is reviewed in this article. Epidemiological and
      (randomized) clinical trials suggest that HHCY increases fracture risk, but has
      minor effects on bone mineral density. Measurement of biochemical bone turnover
      markers indicates a shift of bone metabolism towards bone resorption. Animal
      studies confirm these observations showing a reduced bone quality and stimulation
      of bone resorption in hyperhomocysteinemic animals. Homocysteine (HCY) has been
      found to accumulate in bone by collagen binding. Cell culture studies demonstrate
      that high HCY levels stimulate osteoclasts but not osteoblasts, indicating again
      a shift of bone metabolism towards bone resorption. Regarding B-vitamins, only a
      few in vivo studies with equivocal results have been published. However, two
      large cell culture studies confirm the results obtained with exogenous HCY
      administration. In addition, HHCY seems to have adverse affects on extracellular
      bone matrix by disturbing collagen crosslinking. In conclusion, existing data
      suggest that HHCY (and possibly B-vitamin deficiencies) adversely affects bone
      quality by a stimulation of bone resorption and disturbance of collagen
      crosslinking.

PMID- 18067448
TI  - Homocysteine, brain natriuretic peptide and chronic heart failure: a critical
      review.
AB  - Chronic heart failure (CHF) is a major public health problem causing considerable
      morbidity and mortality. Recently, plasma homocysteine (HCY) has been suggested
      to be significantly increased in CHF patients. This article reviews the relation
      between hyperhomocysteinemia (HHCY) and CHF. Clinical data indicate that HHCY is
      associated with an increased incidence, as well as severity, of CHF. In addition,
      HCY correlates with brain natriuretic peptide (BNP), a modern biochemical marker
      of CHF, which is used for diagnosis, treatment guidance and risk assessment.
      Animal studies showed that experimental HHCY induces systolic and diastolic
      dysfunction, as well as an increased BNP expression. Moreover,
      hyperhomocysteinemic animals exhibit an adverse cardiac remodeling characterized
      by accumulation of interstitial and perivascular collagen. In vitro superfusion
      experiments with increasing concentrations of HCY in the superfusion medium
      stimulated myocardial BNP release independent from myocardial wall stress. Thus,
      clinical and experimental data underline a correlation between HHCY and BNP
      supporting the role of HHCY as a causal factor for CHF. The mechanisms leading
      from an elevated HCY level to reduced pump function and adverse cardiac
      remodeling are a matter of speculation. Existing data indicate that direct
      effects of HCY on the myocardium, as well as nitric oxide independent vascular
      effects, are involved. Preliminary data from small intervention trials have
      initiated the speculation that HCY lowering therapy by micronutrients may improve
      clinical as well as laboratory markers of CHF. In conclusion, HHCY might be a
      potential etiological factor in CHF. Future studies need to explore the
      pathomechanisms of HHCY in CHF. Moreover, larger intervention trials are needed
      to clarify whether modification of plasma HCY by B-vitamin supplementation
      improves the clinical outcome in CHF patients.

PMID- 18067449
TI  - Hyperhomocysteinemia, DNA methylation and vascular disease.
AB  - Hyperhomocysteinemia (HHcy) has been established as a potent independent risk
      factor for cardiovascular disease (CVD) and the underlying mechanism is largely
      unknown. We were the first to propose that hypomethylation is the key biochemical
      mechanism by which homocysteine (Hcy) inhibits endothelial cell (EC) growth. We
      reported that clinically relevant concentrations of Hcy (10-50 micromol/L) exerts
      highly selective inhibitory effects on cyclin A transcription and EC growth
      through a hypomethylation related mechanism, which blocks cell cycle progression
      and endothelium regeneration. Recently, we demonstrated that Hcy reduces DNA
      methyltransferase 1 (DNMT1) activity and demethylates cyclin A promoter leading
      to cyclin A chromatin remodeling. We found that adenovirus-transduced DNMT1 gene
      expression reverses the inhibitory effect of Hcy on cyclin A expression and EC
      growth inhibition. We hypothesize that DNA hypomethylation is a key biochemical
      mechanism responsible for Hcy-induced cyclin A suppression and growth inhibition
      in EC and contributes to CVD.

PMID- 18067450
TI  - Hyperhomocysteinemia: association with renal transsulfuration and redox signaling
      in rats.
AB  - Despite substantial evidence indicating the association of hyperhomocysteinemia
      (hHcys) and end-stage renal disease (ESRD), the pathogenic role of increased
      plasma homocysteine (Hcys) levels in the progression of ESRD remains unclear.
      This review will briefly summarize recent findings regarding the role of hHcys in
      the development of glomerulosclerosis, the association of hHcys with reduced
      renal transsulfuration and Hcys-induced changes of redox signaling in the
      development of glomerulosclerosis in rat kidneys. Based on these results, it is
      concluded that hHcys is implicated in glomerular sclerosis in hypertension,
      elevated plasma Hcys in Dahl salt-sensitive (SS) hypertensive rats is due to
      downregulation of cystathionine beta-synthase (CBS) expression and consequent
      abnormality of transsulfuration in the kidney compared with normotensive rats.
      Hcys-induced superoxide (O(2)(*-)) production by activation of NADPH oxidase as a
      triggering mechanism contributes to the effects of Hcys on the homeostasis of
      extracellular matrix and consequent sclerosis in the glomeruli, and NADPH oxidase
      activation by Hcys is associated with enhanced Rac GTPase activity.

PMID- 18067451
TI  - Importance of folate-homocysteine homeostasis during early embryonic development.
AB  - Although the beneficial effects of maternal folate supplementation in the
      periconceptional period have been shown to prevent neural tube defects,
      congenital heart defects and orofacial clefts, the exact protective mechanism of
      folates remains unknown. Folates affect DNA synthesis, amino acid metabolism and
      methylation of genes, proteins and lipids via S-adenosylmethionine-mediated one
      carbon transfer reactions. Our laboratory has created several mouse knock out
      models of folate transport using gene targeting to inactivate folate receptor 1
      (Folr1), folate receptor 2 (Folr2) and reduced folate carrier 1 (Slc19a1) genes.
      Gene ablation of both Folr1 and Slc19a1 leads to lethality, but with maternal
      folate supplementation, nullizygous embryos for both genes present with neural
      tube defects (NTDs) and congenital heart defects (CHDs). Folr1 nullizygous mice
      also exhibit orofacial clefts when the dams are provided with low folate
      supplementation during pregnancy. Finally, women with NTD-affected pregnancies
      have been reported to have high autoantibody titers against the folate receptor,
      potentially inhibiting the transport of folate to the developing embryo. This may
      be an explanation for some of the folate-responsive NTDs and perhaps other
      congenital malformations. Herein, we propose how homocysteinylation of the folate
      receptor may contribute to generation of these autoantibodies against the folate
      receptor.

PMID- 18067452
TI  - Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to
      total cobalamin and methylmalonic acid.
AB  - BACKGROUND: Cobalamin-saturated transcobalamin, also called holotranscobalamin
      (holoTC), constitutes only between 6% and 20% of total plasma B(12). Serum
      concentration of holoTC is a new marker in laboratory diagnosis of cobalamin
      deficiency. We tested the utility of holoTC in assessing vitamin B(12) status.
      METHODS: We measured concentrations of holoTC and methylmalonic acid (MMA) in
      1018 serum samples that were referred to our laboratory for total cobalamin
      testing. RESULTS: Concentrations of MMA were lower in females compared to males
      and this difference was no more significant after adjusting for serum creatinine.
      Moreover, age was associated with higher concentrations of serum MMA, higher
      holoTC and slightly higher concentrations of total cobalamin. Higher
      concentrations of serum creatinine were associated with higher concentrations of
      MMA and holoTC. However, no association between serum creatinine and total
      cobalamin was observed. Only subjects with normal serum creatinine showed a
      negative correlation between serum holoTC and MMA (r= -0.36, p<0.001). In
      subjects with MMA > or =300 nmol/L and holoTC < or =35 pmol/L, concentrations of
      total cobalamin were well within the normal range (median; 25th/75th
      percentiles=212; 171/272 pmol/L). Receiver operating characteristic (ROC) curve
      analysis displayed a higher sensitivity and specificity for holoTC compared with
      vitamin B(12) for detecting concentrations of MMA > or =300 nmol/L in individuals
      with normal renal function. CONCLUSIONS: Compared to total cobalamin, we observed
      a better performance of holoTC assay in detecting elevated concentrations of MMA
      in subjects with normal renal function. The majority of subjects with combined
      low holoTC and elevated MMA had normal concentrations of total cobalamin. HoloTC
      can be used as a first line parameter in detecting cobalamin deficiency.

PMID- 18067453
TI  - Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and
      dihydrofolate reductase.
AB  - BACKGROUND: Impairments in folate-mediated one-carbon metabolism are associated
      with pathologies and developmental anomalies, including cardiovascular disease,
      cancer, neurological disorders and neural tube defects. The mechanisms that
      detail the role of folate and one-carbon metabolism in these disorders remain to
      be established. Folate deficiency impairs folate-dependent thymidylate
      biosynthesis resulting in depleted dTTP levels, increased rates of uracil
      incorporation into DNA and genomic instability. Folate-dependent enzymes involved
      in the de novo thymidylate pathway include cytoplasmic serine
      hydroxymethyltransferase (cSHMT), thymidylate synthase (TS) and dihydrofolate
      reductase (DHFR). Previously, we demonstrated that cSHMT-derived folate activated
      one-carbon units are preferentially incorporated into thymidylate, and we
      provided evidence that this was achieved through modification with small
      ubiquitin-like modifier (SUMO) enabling SUMO-dependent nuclear localization of
      cSHMT during S-phase. METHODS AND RESULTS: Here, we provide evidence that TS and
      DHFR are also substrates for UBC9-catalyzed SUMOylation in vitro by SUMO-1.
      CONCLUSIONS: The SUMOylation of cSHMT, TS and DHFR provides a mechanism by which
      all three enzymes in the thymidylate synthesis pathway are directed and
      compartmentalized in the nucleus.

PMID- 18067454
TI  - Decreased p66Shc promoter methylation in patients with end-stage renal disease.
AB  - BACKGROUND: p66Shc is a stress response protein and partially regulated by
      epigenetic modifications. Mice lacking p66Shc have reduced atherosclerosis,
      increased resistance to oxidative stress and a prolonged life time. The aim of
      the present study was to compare promoter methylation of the p66Shc gene between
      healthy controls and patients with end-stage renal disease (ESRD). There are two
      reasons for studying patients with ESRD. First, patients with ESRD have a
      disturbed homocysteine metabolism, and second an increased risk of morbidity and
      mortality from cardiovascular disease is a constant finding in these patients.
      METHODS: In our study, we measured fasting levels of homocysteine, S
      adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and 8-isoprostane in 22
      patients and in 26 healthy, age- and sex-matched controls. The methylation of the
      p66Shc promoter and Line-1, as surrogate marker of whole genome methylation was
      quantified in peripheral blood mononuclear cells. RESULTS: In comparison to the
      control group, homocysteine, SAM, SAH, 8-isoprostane and whole genome methylation
      were significantly elevated in ESRD patients, while the p66Shc promoter
      methylation was significantly reduced. A significant correlation was found
      between SAH and p66Shc promoter methylation in the patient group. This
      observation underlines the role of SAH as a potent inhibitor of
      methyltransferases. Using backward regression analysis, we demonstrated that 8
      isoprostane has a significant influence on p66Shc promoter methylation. In the
      control group and in patients with ESRD, increasing 8-isoprostane levels were
      linked to an elevated promoter methylation. CONCLUSIONS: Under physiological
      conditions, based on the results of the control group, the p66Shc expression is
      more silenced through epigenetic modifications. The atherosclerotic risk is
      dramatically increased in ESRD patients; therefore, our experimental results of
      methylation are in accordance with the clinical situation.

PMID- 18067462
TI  - Quercetinase pirin makes poliovirus replication resistant to flavonoid quercetin.
AB  - Flavonoid quercetin and its derivative, methylquercetin, inhibit the replication
      of poliovirus in several cell lines. Here, we show that replication of poliovirus
      is inhibited by quercetin and that the extent of this inhibition depends on the
      intracellular content of pirin, a quercetinase. HeLa cells contain higher content
      of pirin protein than normal kidney human epithelial (NKE) or 293 cells do.
      Poliovirus replication in HeLa cells is significantly more resistant to quercetin
      than its replication in NKE and 293 cells. Overexpression of pirin reduced
      antiviral inhibitory effect of quercetin, while siRNA-induced suppression of
      pirin level made poliovirus replication more sensitive to the flavonoid. The
      results suggest that quercetinase activity of pirin determines the resistance of
      poliovirus infection to quercetin.

PMID- 18067463
TI  - Relationship of preventive health practices and health literacy: a national
      study.
AB  - OBJECTIVE: To identify relationships between the health literacy and self
      reported preventive health practices of US adults. METHODS: Measured health
      literacy and preventive health practices for a nationally representative sample
      of adults (N = 18,100) and conducted probit regression analyses after controlling
      for age, gender, race/ethnicity, poverty level, insurance status, self-reported
      health status, and oral reading fluency. RESULTS: Low literacy was associated
      with a decreased likelihood of using most preventive health measures under study
      for adults aged 65 and older, but not for adults of 2 younger age groups.
      CONCLUSION: The relationship between health literacy and preventive health
      practices varied substantially by adult age group.

PMID- 18067464
TI  - Fact or wishful thinking? Biased expectations in "I think I look better when I'm
      tanned".
AB  - OBJECTIVE: To examine the impact of tanned female images on respondents'
      perceptions of attractiveness, healthiness, and height and weight estimations.
      METHOD: A 3 (light, medium, or dark tan) by 2 (male or female respondent)
      experimental design. RESULTS: Only male respondents perceived the dark-tanned
      woman as more physically attractive and thinner than both light- and medium
      tanned women. Men also perceived the dark-tanned woman as more interpersonally
      attractive and healthier than the medium-tanned woman. CONCLUSIONS: Campaigns
      targeted at males need to reduce the perceptions that tanned females are
      healthier, thinner, and more attractive. Educational efforts targeting females
      need to reduce attraction-based motivations.

PMID- 18067465
TI  - Determinants of physical activity in low-income, overweight African American
      girls.
AB  - OBJECTIVES: To examine the relationship between puberty, sedentary behaviors, and
      psychosocial influences with intention for physical activity (PA) and PA.
      METHODS: Low-income, overweight African American girls (n=72) completed 5
      questionnaires that assessed PA, sedentary behaviors, and psychosocial
      influences. Puberty was assessed using Tanner stages. Multiple linear regression
      was used to examine the relationships between these measures and intention for
      PA. RESULTS: Puberty was significantly associated with lower intention for PA,
      whereas health beliefs such as "staying in shape" and social support were
      significantly associated with greater intention for PA. CONCLUSIONS: Puberty,
      health beliefs for PA, and social support from parents and peers were significant
      predictors of intention for PA in low-income, overweight African American girls.

PMID- 18067466
TI  - Perceived barriers to community-based health promotion program participation.
AB  - OBJECTIVES: To examine barriers and self-efficacy relative to attendance at a
      cardiovascular risk reduction program. METHODS: Subjects (N=161) represented 3
      levels of program participation: full, minimum, and none. Survey scales for
      barriers to attendance and health behavior change, food security, and self
      efficacy for nutrition and physical activity were administered. RESULTS: Minimum
      and no-exposure participants perceived significantly more barriers to attendance
      than did the full-exposure participants (P<0.05); barriers to health behavior
      change were not significantly different. Self-efficacy for nutrition and physical
      activity were not significantly different among the groups. CONCLUSIONS: Health
      promotion programs need to consider anytime, any place modes of program delivery
      to address "program day and time" and "no time to attend" barriers perceived by
      target audiences.

PMID- 18067467
TI  - Correlates of smoking before, during, and after pregnancy.
AB  - OBJECTIVES: To use recent, national data to examine correlates of smoking before,
      during, and after pregnancy; quitting smoking during pregnancy; and relapsing by
      24 months postpartum. METHODS: Multivariate logistic regression models used data
      from the Early Childhood Longitudinal Study-Birth Cohort and accounted for
      relevant socio-demographic, clinical, and contextual covariates. RESULTS:
      Although socio-demographic characteristics including education, income,
      race/ethnicity, and marital status were associated with smoking at all time
      points, contextual factors including alcohol consumption, breast-feeding, and
      living with other smokers were also strongly associated with smoking, quitting,
      and relapsing. CONCLUSIONS: Results of this study may facilitate the creation of
      more targeted interventions focusing on women at highest risk for smoking during
      this critical period.

PMID- 18067468
TI  - Associations between tobacco marketing and use among urban youth in India.
AB  - OBJECTIVES: To study if receptivity and exposure to tobacco marketing are
      correlated with tobacco use and psychosocial risk factors for tobacco use among a
      sample of urban Indian youth. METHODS: Analysis of cross-sectional survey data
      from Project MYTRI, a group randomized intervention trial, in Delhi and Chennai,
      India, collected from sixth and eighth graders (n=11,642), in 32 schools in 2004.
      RESULTS: Exposure to tobacco advertisements and receptivity to tobacco marketing
      were significantly related to increased tobacco use among students. CONCLUSION:
      This association suggests the need to strengthen policy and program-based
      interventions in India to reduce the influence of such exposures.

PMID- 18067469
TI  - Physical self-perception, body dysmorphic disorder, and smoking behavior.
AB  - OBJECTIVE: To examine the relationship of physical self-perceptions, body
      dysmorphic disorder (BDD), and smoking status among college-age women. METHODS: A
      cross-sectional study design was selected to study women (n= 364) who completed a
      79-item questionnaire that measured physical self-perceptions and BDD. RESULTS:
      BDD items, including fear of weight gain, social avoidance and comparison, along
      with perceptions of physical health and medical use, predicted smoking behavior.
      CONCLUSIONS: Negative perceptions of physical health and 3 diagnostic components
      associated with BDD may moderate smoking cessation attempts and maintain smoking
      behavior among college-age women.

PMID- 18067470
TI  - Social cognitive theory variables mediation of moderate exercise.
AB  - OBJECTIVE: To identify the degree to which the social cognitive theory constructs
      targeted by the Planning to Be Active Program (PBA) were mediators of moderate
      intensity exercise. METHODS: High school students in treatment and comparison
      groups received activity-based physical education. The treatment group also
      received PBA, which develops self-regulation skills to promote leisure-time
      exercise. RESULTS: PBA increased self-regulation scores, social situation scores,
      and moderate-intensity exercise. Self-regulation and social situation mediated
      moderate-intensity exercise at posttest. CONCLUSIONS: As mediators, self
      regulation and social situation help explain how PBA produces increases in
      moderate-intensity exercise.

PMID- 18067471
TI  - Meta-analysis of health behavior change interventions in type 1 diabetes.
AB  - OBJECTIVES: To meta-analyze research testing interventions to improve health
      behaviors including exercise among adults with type 1 diabetes. METHODS: Multiple
      literature-searching strategies identified published and unpublished studies
      reporting glycated hemoglobin outcomes. Fixed- and random-effects meta-analyses
      included moderator effects. RESULTS: Data were synthesized across 1435 subjects.
      The overall effect size was 0.26. This translates into a reduction of 0.33 in
      mean HbA1c levels between treatment (8.47%) and control (8.80%) groups. Effect
      sizes were larger with more females, lower body mass index, higher baseline
      HbA1c, and interventions targeting multiple behaviors. CONCLUSIONS: Behavior
      change interventions improve metabolic control in type 1 diabetes.

PMID- 18067472
TI  - Transfusional myocardial iron overload in myelodysplastic patients.

PMID- 18067473
TI  - Should prophylactic granulocyte-colony stimulating factor be used in multiple
      myeloma patients developing neutropenia under lenalidomide-based therapy?
AB  - Lenalidomide combined with dexamethasone has significant clinical activity in the
      treatment of multiple myeloma (MM). In previous clinical trials lenalidomide
      induced neutropenia was a frequent side-effect, often leading to treatment delays
      and dose reductions. We describe three MM patients treated with lenalidomide plus
      dexamethasone, which developed grade 3/4 neutropenia during the initial cycles,
      but without serious infection. Administration of granulocyte-colony stimulating
      factor (G-CSF) for 3 d prevented further neutropenia, treatment delays, dose
      reductions, or infectious complications during the following cycles.
      Consequently, G-CSF could be effective in preventing further neutropenia-related
      complications without compromising treatment efficacy in MM patients with
      lenalidomide-induced neutropenia.

PMID- 18067474
TI  - Paracoccidioidomycosis presenting in the UK.

PMID- 18067475
TI  - Low to moderate cumulative doses of pegylated liposomal doxorubicin in the
      treatment of classic Kaposi sarcoma in elderly patients with comorbidities.

PMID- 18067476
TI  - Prevalence and risk factors for atopic dermatitis in preschool children.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common condition in infancy which usually
      disappears by 3 years of age in a significant proportion of children. The
      prognosis is mostly determined by severity and presence of atopic sensitization.
      OBJECTIVES: To investigate prevalence of AD, comorbidities and risk factors in a
      population of preschool children aged 3-5 years. METHODS: Children in
      kindergartens were evaluated. The International Study of Asthma and Allergies in
      Childhood written questionnaire (WQ) was used, with additional questions on risk
      factors. Atopy was investigated by skin prick tests. RESULTS: One thousand, four
      hundred and two valid WQs (92% response rate) were returned for evaluation. The
      prevalence of AD symptoms in the last 12 months in the whole population was 18.1%
      (254 cases). Seventy-two per cent of these children presented AD-specific
      localizations. The prevalence of eczema as a doctor's diagnosis in the total
      population was 15.4%. Positive atopic sensitization was present in 18.6% of the
      total and in 32.2% of the AD study population, respectively. Multiple
      sensitivities were observed in 58.2% of sensitized children. The prevalence of
      sensitization demonstrated that the most common sensitizing allergens in children
      with AD were mites and grass pollen. Rhinitis symptoms and wheezing were present
      in 32.2% and 24.2%, respectively, of children with AD. Allergic sensitization to
      egg, cat, grass pollen and mites, as well as the presence of symptoms of
      rhinitis, and a positive family history of atopy were all significant risk
      factors for AD. CONCLUSIONS: The study demonstrates a high prevalence of AD and a
      close relationship with rhinitis symptoms. Significant risk factors for AD were
      sensitization to food or inhalant allergens as well as parental history of atopy.

PMID- 18067477
TI  - Cutaneous neonatal lupus erythematosus in four siblings.

PMID- 18067478
TI  - Development and validation of the Dermatomyositis Skin Severity Index.
AB  - BACKGROUND: Dermatomyositis is an autoimmune inflammatory muscle disease with
      characteristic cutaneous findings of heliotrope eruption, Gottron's papules and a
      photodistributed eruption with poikiloderma. OBJECTIVES: To develop and validate
      a tool to assist with objective assessment of the skin disease of
      dermatomyositis. METHODS: A skin severity index was developed; content validity
      was evaluated by a panel of experts, and construct validity was assessed by
      convergence with other measures of disease severity including physician's global
      assessment of disease, specific skin disease changes (ulceration, poikiloderma
      and pruritus), and quality of life. Test and retest reliability and interobserver
      reproducibility were determined. RESULTS: In total, 98 subjects were enrolled.
      The Dermatomyositis Skin Severity Index (DSSI) showed significant correlation to
      the physician's global assessment, assessments of poikiloderma and self
      assessment of pruritus. Inter-rater reliability showed strong correlations from
      0.73 to 1. Test-retest (intrarater reliability) was completed on 33 subjects, and
      showed correlations above 0.75. The ability of this tool to detect clinical
      changes with treatment has not been fully evaluated. CONCLUSIONS: The DSSI is a
      valid and reliable measure of skin disease severity in dermatomyositis and can be
      used in future clinical trials as an assessment tool.

PMID- 18067479
TI  - The effect of mechanical strain on protease production by keratinocytes.
AB  - BACKGROUND: Intact skin is under constant tension, transmitted from the
      underlying dermis, but when tension is lost (i.e. upon wounding) protease
      activity is upregulated. OBJECTIVES: To investigate the effect of mechanical
      strain on protease production by both normal and transformed keratinocytes in
      vitro. METHODS: Keratinocytes were seeded on to membranes precoated with either
      type I or type IV collagen. After 48 h medium was replaced with serum-free medium
      and mechanical strain was applied. RESULTS: Mechanical strain resulted in
      decreased urokinase-type plasminogen activator (uPA) production by normal human
      keratinocytes (P<0.05) but increased production by transformed keratinocytes
      (P<0.05) cultured on type I and type IV collagen. CONCLUSIONS: Differential
      production of uPA by normal and transformed keratinocytes is relevant in the
      context of normal function, wound healing and tumorigenesis.

PMID- 18067480
TI  - A splicing mutation in the COL7A1 gene causes autosomal dominant dystrophic
      epidermolysis bullosa pruriginosa.

PMID- 18067481
TI  - Proteoglycan expression patterns in human hair follicle.
AB  - BACKGROUND: Proteoglycans (PGs) are known to play key roles in many cellular
      signalling pathways involved in hair follicle biology. Although some PG core
      proteins have previously been described in adult human hair follicles, their
      glycosaminoglycan (GAG) moieties have been less studied. OBJECTIVES: To add
      knowledge about PG core protein and GAG distributions in human anagen hair
      follicle and, for selected follicles, during catagen. METHODS: We used
      immunohistochemistry and immunohistofluorescence to revisit the expression
      pattern of GAG chains and core proteins in human hair follicle. The studied
      epitopes included CD44v3, syndecan-1, perlecan, versican, aggrecan, biglycan,
      heparan sulphate (HS), chondroitin sulphate (CS), dermatan sulphate (DS) and
      keratan sulphate (KS). RESULTS: The membrane PGs syndecan-1 and CD44v3 were
      respectively detected in the epithelial part of whole hair and in the outer root
      sheath basal layer. The dermal part of the hair follicle contained high amounts
      of extracellular PGs such as perlecan, versican, aggrecan, biglycan and their
      saccharidic moieties, namely HS, CS, DS and KS. We also observed a variable
      distribution of these components along the hair follicle. Especially, we noted a
      PG impoverishment at the very bottom of the anagen bulb. Moreover, while type D
      chondroitin expression remained unaffected, 4C3-CS and PG4-CS/DS epitopes
      respectively decreased in the dermal papilla and the connective tissue sheath, at
      the onset of catagen. CONCLUSIONS: GAG and PG expression along the human anagen
      hair follicle was characterized by (i) discontinuities mainly affecting the
      basement membrane and (ii) disappearance of some epitopes at catagen onset. These
      results are discussed in term of functionalities in nutrient diffusion, cell
      proliferation and differentiation, and hair protection.

PMID- 18067482
TI  - Inpatient management of psoriasis: a multicentre service review to establish
      national admission standards.
AB  - BACKGROUND: Some patients with psoriasis may require hospital admission to
      stabilize their condition, although the role of inpatient management is changing
      given recent advances in therapeutic options, emphasis on community-based care
      for chronic conditions and limited healthcare resources. There is a need for
      evidence-based national standards for inpatient management of psoriasis taking
      account of factors that predict length of stay. OBJECTIVES: To determine which
      factors predict length of stay for patients with psoriasis requiring inpatient
      hospital care with a view to setting evidence-based standards for inpatient
      psoriasis management. METHODS: A multicentre service review was conducted on all
      psoriasis admissions over a 9-month period in four dermatology centres in the
      U.K. We collected data on admission, at discharge and, where possible, at 3
      months following discharge. Psoriasis severity was assessed using four validated
      scoring systems, including Psoriasis Area and Severity Index (PASI) and
      Dermatology Life Quality Index. We also recorded length of stay and treatment
      details. RESULTS: Length of stay varied widely between the four centres, but was
      similar in the two centres which received a high proportion of tertiary referrals
      for severe psoriasis (mean 19.7 days, range 1-78, analysis of variance P=0.002).
      Disease severity, measured by PASI, on admission (mean 15.7, interquartile range
      8.3-20.8) was significantly higher in the tertiary centres (P<0.0001). However,
      there was no significant difference in PASI between centres on discharge. The
      admission PASI was significantly associated with length of stay (r=0.2, P=0.02).
      There was no significant correlation between other measures of disease severity
      and length of stay. CONCLUSIONS: Disease severity on admission for patients with
      psoriasis is greater in tertiary referral centres for psoriasis and is directly
      associated with length of stay. Length of stay should be used in conjunction with
      clinical measures such as PASI improvement to set national standards for quality
      in secondary care.

PMID- 18067483
TI  - A comparison of twice-daily calcipotriol ointment with once-daily short-contact
      dithranol cream therapy: quality-of-life outcomes of a randomized controlled
      trial of supervised treatment of psoriasis in a day-care setting.
AB  - BACKGROUND: Calcipotriol ointment and short-contact dithranol cream therapy are
      well-established topical treatments for psoriasis. Quality of life, i.e. the
      physical, psychological, and social functioning and well-being of the patient,
      has become an essential outcome measure in chronic skin disease. OBJECTIVES: To
      compare the quality-of-life outcomes of calcipotriol ointment with that of short
      contact dithranol cream in a supervised treatment regimen, and to determine the
      degree of improvement in quality of life these topical treatments can accomplish.
      METHODS: In a multicentre randomized controlled trial in six centres in the
      Netherlands, 106 patients with chronic plaque psoriasis were included, 54
      receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in
      a 12-week intensive treatment programme. Patients were treated at the day-care
      centre, using the care instruction principle of daily visits during the first
      week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was
      assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form
      General Health Survey (SF-36). RESULTS: At the end of treatment, no statistically
      significant differences were found between the calcipotriol and the dithranol
      group in any of the quality-of-life domains or scales of the Skindex-29 and the
      SF-36. Over time, a significant improvement of quality of life was found on all
      three scales of the dermatology-specific Skindex-29, predominantly of a moderate
      magnitude. In the calcipotriol group, a significant change of a small magnitude
      was found in the Physical Component Summary of the SF-36. No significant changes
      were found in the Mental Component Summary (or on any of the eight scales
      composing the questionnaire) of the SF-36. CONCLUSIONS: The hypothesis was
      confirmed, that no statistically significant differences in improvement of
      quality of life could be found between calcipotriol ointment and dithranol short
      contact cream in a day-care setting. Given this result, both calcipotriol and
      dithranol can be welcome alternatives for the patient. Calcipotriol, being more
      practical and patient friendly, can be considered as a first-line approach in
      clinical practice. However, in patients recalcitrant to calcipotriol and/or other
      topical treatments, preference should be given to the dithranol regimen. Topical
      treatment in combination with interventions explicitly focusing on improvement of
      coping behaviour and psychosocial functioning may further increase the degree of
      improvement in the psychosocial domains of quality of life. The results of this
      study are likely to give further evidence to the notion that the generic SF-36 is
      little or not responsive to small to moderate changes in quality of life in mild
      to moderate psoriasis.

PMID- 18067484
TI  - The association between alcohol consumption and contact sensitization in Danish
      adults: the Glostrup Allergy Study.
AB  - BACKGROUND: Population-based epidemiological studies have indicated that alcohol
      consumption is associated with IgE-mediated immune diseases (i.e. allergic
      rhinitis, asthma and urticaria). These studies have been strongly supported by
      several immunological studies. Furthermore, an inhibitory effect of alcohol
      consumption on the development of delayed-type hypersensitivity has been shown in
      healthy controls. However, a possible association between contact sensitization
      and alcohol consumption in a general population has never been reported.
      OBJECTIVES: To investigate whether alcohol consumption is associated with contact
      sensitization in a general population. METHODS: In 1990, self-reported
      consumption of alcohol and patch testing results were assessed in 1112 subjects,
      aged 15-69 years, participating in a population-based cross-sectional study in
      Glostrup, Denmark. In 1998, they were invited to a follow-up and 734 were re
      examined (participation rate 69.0%). Adjustment for potential confounders was
      performed by using logistic regression analyses. RESULTS: Women who reported no
      consumption of alcoholic drinks per week were more likely to develop contact
      sensitization (adjusted odds ratio 2.12, 95% confidence interval 0.98-4.61)
      during a 8-year follow-up period. A positive trend among women was detected
      (P=0.045). CONCLUSIONS: These data support the hypothesis that alcohol
      consumption leads to IgE-mediated immune responses rather than delayed-type
      hypersensitivity reactions. It is probable that alcohol consumption prevents the
      development of contact sensitization. Further epidemiological studies are
      warranted.

PMID- 18067485
TI  - Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation
      and long-term persistence in nephrogenic systemic fibrosis.
AB  - BACKGROUND: Gadolinium (Gd)-based magnetic resonance contrast agents (GBMCA),
      including gadodiamide, have been identified as the probable causative agents of
      the serious disease, nephrogenic systemic fibrosis (NSF). OBJECTIVES: To
      investigate retained Gd-containing deposits in skin biopsies from patients with
      NSF and to determine their relative concentrations over time from administration
      of GBMCA. METHODS: An investigator-blinded retrospective study, analysing 43 skin
      biopsies from 20 patients with gadodiamide-related NSF and one NSF-negative
      gadodiamide-exposed dialysis patient, ranging from 16 days to 1991 days after Gd
      contrast dose. Utilizing automated quantitative scanning electron
      microscopy/energy-dispersive X-ray spectroscopy we determined the concentration
      of Gd and associated elements present as insoluble deposits in situ in the
      tissues. RESULTS: We detected Gd in skin lesions of all 20 patients with NSF,
      whereas Gd was undetectable in the NSF-negative patient. Gd concentration
      increased over time in 60% of patients with multiple sequential biopsies (n=10),
      decreasing only when the initial sampling time was >23 months after first
      gadodiamide dose. All Gd-containing deposits contained phosphorus, calcium and
      sodium. The ratio of Gd to calcium in tissue deposits correlated positively with
      the gadodiamide dose and with serum ionized calcium at the time of Gd exposure.
      CONCLUSIONS: These findings demonstrate the in vivo release (through
      transmetallation) of the toxic free Gd3+ from gadodiamide, and its retention in
      apatite-like deposits. We suggest that Gd may be mobilized over time from bone
      stores, explaining variably delayed onset of NSF and increasing skin
      concentration over time in patients with NSF.

PMID- 18067486
TI  - C-reactive protein in psoriasis.

PMID- 18067487
TI  - Light and scanning electron microscopic study on the blood vascular system of the
      donkey placenta.
AB  - The donkey placenta is diffuse and epitheliochorial with numerous
      microplacentomes consisting of a fetal microcotyledonary and a maternal
      microcaruncular part. The microplacentomal vasculature during the last third of
      pregnancy has been investigated by light microscopy in comparison to scanning
      electron microscopy of the materno-fetal contact surface and corrosion casts of
      blood vessels after plastic instillation from either the microcotyledonary or the
      microcaruncular side, and, for the first time in a perissodactyle, from both
      sides. Morphological data were semiquantitatively evaluated. The supplying parts
      of both, the microcotyledonary and the microcaruncular vascular system are
      strictly proximo-distally oriented, thus reaching the capillary systems or
      working parts in the shortest way possible. The straight course of the
      vasculature, particularly on the fetal side, suggests the occurrence of venulo
      arteriolar back diffusion. The fetal capillary system consists of convolutes
      confronting the maternal septal capillary complexes in a countercurrent way. This
      materno-fetal blood flow interrelationship is highly efficient in terms of
      placental exchange, which is further supported (1) by dilations and increasing
      coiling of the fetal venular capillary limbs in particular and (2) by a decrease
      in the interhaemal distance from 12.5 to 7.2 microm between the two capillary
      systems. Besides the countercurrent blood flow interrelationship, some maternal
      branch arterioles reach the septal capillary system from the maternally oriented
      pole of the microplacentome or microcaruncle, respectively, resulting in the less
      efficient crosscurrent blood flow. Hence, in the donkey placenta fetal and
      maternal blood vessels meet in a mix of countercurrent and crosscurrent flow
      patterns.

PMID- 18067488
TI  - Recruiting and retaining young people as voluntary blood donors.
AB  - OBJECTIVES: Reasons for predonation deferral of young potential donors and
      prospects of recruiting and retaining young people (age 18-29) as voluntary blood
      donors were studied. STUDY DESIGN AND METHODS: Three different sources of data
      were analysed: (i) the subsequent donation history of 2057 donors who started
      their donation career at the Blood Bank of Oslo (BBO) in 1999, age and gender of
      all new donors accepted for donation at BBO in 2004 was retrieved from electronic
      data files; (ii) data on reasons for predonation deferral, age and gender of all
      deferred prospect donors at BBO in 2004 was obtained from original screening
      questionnaires; and (iii) results from a national telephone survey of the general
      population's attitudes regarding blood donation, conducted in 2005. RESULTS:
      Twenty-five per cent of the first-time donors recruited in 1999 remained active
      in 2005, but the percentage was higher among older than younger donors. Change of
      residency was the most frequent reason for termination of donation among young
      donors. Young prospect donors were more frequently than older ones deferred for
      lifestyle-related reasons. Prospect donors older than 30 years were more
      frequently deferred for health-related reasons. A large proportion (57.7%) of
      young adults reported a favourable attitude towards becoming blood donors. Lack
      of a personal request (not being asked) was the most frequently reported reason
      for not giving blood among young people with no donation record. Only a minor
      proportion of young non-donors considered themselves disqualified from donating
      blood due to health status. CONCLUSIONS: Lifestyle-related eligibility criteria
      and changes of residency pose problems for recruitment and retention of young
      donors. However, a large proportion of young adults state that they are able and
      willing to donate blood; therefore, the prospects of recruiting young people as
      voluntary blood donors seem generally positive.

PMID- 18067489
TI  - The acceptability to women in Mombasa, Kenya, of the donation and transfusion of
      umbilical cord blood for severe anaemia in young children.
AB  - BACKGROUND AND OBJECTIVES: Severe anaemia, for which a blood transfusion can be
      life saving, is common in hospitalized children in sub-Saharan Africa but blood
      for transfusion is often in short supply. Umbilical cord blood is usually thrown
      away but could be a useful source of red cells for small volume transfusions in
      young children in this setting. The objective of this study was to evaluate the
      attitudes of women using the maternity services of the provincial hospital in
      Mombasa, Kenya, towards cord blood donation and transfusion, and essential
      aspects of this process including informed consent and the acceptability of
      screening for human immunodeficiency virus (HIV) infection. MATERIALS AND
      METHODS: A structured questionnaire was developed based on data provided by focus
      group discussions with women attending the hospital's maternity unit and
      administered to women who had recently delivered at the hospital. RESULTS: Of the
      180 women who completed a questionnaire, the donation and transfusion of cord
      blood were acceptable to 81% and 78%, respectively. Ninety per cent of women who
      supported cord blood donation were willing to undergo further HIV testing at the
      time of delivery. Seventy-seven per cent of women wanted informed consent to be
      sought for cord blood donation and 66% of these felt they could make this
      decision alone. CONCLUSION: The donation of umbilical cord blood and its
      transfusion are acceptable to the majority of women delivering at Coast
      Provincial General Hospital, Mombasa. Findings from the study will benefit the
      planned cord blood donation programme at this facility.

PMID- 18067490
TI  - Investigation of the thrombin-generating capacity, evaluated by thrombogram, and
      clot formation evaluated by thrombelastography of platelets stored in the blood
      bank for up to 7 days.
AB  - BACKGROUND AND OBJECTIVES: Transfusion based on the Thrombelastograph (TEG)
      results reduces transfusion requirements in cardiac surgery and in liver
      transplantation. Taking the pivotal role of thrombin generation in the
      coagulation process into consideration, the clinical utility of the TEG may, in
      part, depend on its reflection of the dynamics of thrombin generation. MATERIAL
      AND METHODS: The kinetics of thrombin generation of platelets stored for 2 and 7
      days, respectively, was assessed by calibrated automated thrombogram (CAT) and
      the lag time (min), time to peak (ttPeak; min), peak (nm thrombin) and endogenous
      thrombin potential (ETP; nm thrombin*min) were registered. Clot formation was
      evaluated by TEG and the R time (min), maxial amplitude (MA; mm), time to maximum
      thrombus generation (TMG; min) and maximum thrombus generation (MTG; dynes cm(-2)
      s(-1)) and total thrombus generation (TTG; dyne cm(-2)) were registered. RESULTS:
      Platelets become more procoagulant, evaluated both by TEG and CAT during storage.
      The reduction in CAT lag time and the ttPeak correlated with a decrease in the
      TEG R time and TMG (P < 0.0001) as did the CAT peak thrombin generation and the
      TEG MTG (P = 0.0035). No correlation between ETP and TTG was found (P = 0.65).
      CONCLUSION: The kinetics of thrombin generation, as evaluated by CAT, correlates
      with the thrombus generation, as evaluated by thrombelastography and this may in
      part explain the clinical utility of the TEG in identifying clinically relevant
      coagulopathies, secondary to impaired thrombin generation.

PMID- 18067491
TI  - Red cell transfusion for iron-deficiency anaemia: a retrospective audit at a
      tertiary hospital.
AB  - BACKGROUND AND OBJECTIVES: The role of red cell transfusion in the management of
      iron-deficiency anaemia is controversial. This audit was undertaken to monitor
      the overall transfusion practices of patients admitted to a 600-bed acute
      tertiary hospital with confirmed severe iron deficiency. MATERIALS AND METHODS:
      Data from 615 consecutive patients with iron deficiency and no evidence of iron
      therapy during the period from 1 March 2001 to 30 September 2005 were
      retrospectively reviewed. RESULTS: Of the 615 iron-deficient patients, 39.2% were
      transfused. Overall transfused patients were significantly older (mean 73 years
      old vs. 53 years old; P < 0.0001) with more comorbidities than those not
      transfused. The pretransfusion haemoglobin (Hb) was < 90 g/l in 92.5% compared to
      15.4% of patients not transfused. The post-transfusion Hb was > or = 100 g/l in
      75.0% of patients and > or = 110 g/l in 44.2%. Although currently rare (2.5%
      patients) our speculative data suggest that single red cell transfusions may be
      appropriate in < or = 29% of patients if restrictive thresholds were adopted.
      CONCLUSION: Red cell transfusions are commonly administered to elderly patients
      with severe iron-deficiency anaemia. They may be necessary to alleviate severe
      morbidity until the time at which iron therapy becomes clinically effective.
      However, greater emphasis should be given to restrictive transfusion strategies
      and dosing. Transfusion of single red cell units followed by clinical assessment
      will determine the need for subsequent units and ensure that this valuable
      resource is appropriately used.

PMID- 18067492
TI  - Selection of hematopoietic stem cells with a combination of galactose-bound vinyl
      polymer and soybean agglutinin, a galactose-specific lectin.
AB  - BACKGROUND: Selection of hematopoietic stem cells can be used to prevent graft
      versus-host disease (GVHD) after allograft transplantation. The purpose of the
      study was to examine a novel cell separation system comprising a galactose-bound
      vinyl polymer (Gal-VP) and soybean agglutinin (SBA), a galactose-specific lectin.
      STUDY DESIGN AND METHODS: A vinyl polymer (VP) containing alpha-1,6- and beta-1,4
      linked galactose terminals was used to facilitate cell separation. A VP
      containing an alpha-1,4-linked glucose terminal (alpha-1,4-Glu-VP) was also
      synthesized as a control for alpha-1,6- and beta-1,4-Gal-VP. Peripheral blood
      samples were collected from healthy volunteers and umbilical cord blood cells
      were collected after normal labor. RESULTS: The sugar-VP was adsorbed on the
      surface of various materials. In the presence of SBA, T lymphocytes bound to beta
      1,4-Gal-VP-coated microbeads, but not to alpha-1,4-Glu-VP-coated microbeads. When
      peripheral or cord blood cells were cultured on alpha-1,6-Gal-VP-coated plates,
      most red blood cells, lymphocytes, granulocytes, and monocytes adhered to the
      plate in the presence of 300 mg per mL SBA, whereas few CD34+ cells attached,
      even with 800 mg per mL SBA. CONCLUSION: SBA binds selectively to blood cells by
      recognizing cell-surface sugars, which are dependent on the extent of cellular
      differentiation. Therefore, the combination of alpha-1,6-Gal-VP and SBA might be
      useful for separation of blood cells according to their stage of differentiation
      and lineage.

PMID- 18067493
TI  - Persistence of allografts in the peritoneal cavity after prenatal transplantation
      in mice.
AB  - BACKGROUND: In utero transplantation (IUT) is usually performed by
      intraperitoneal injection, but there is little information regarding the fate of
      intraperitoneally transplanted cells in the first weeks after transplantation.
      STUDY DESIGN AND METHODS: Fetal transplantation was performed in a B6D2F(1)
      (C57BL/6 x DBA/2, H-2(b)/(d)) into C57BL/6 (H-2(b)) murine strain combination at
      the gestational age of 13 days by intraperitoneal injection of light-density
      marrow cells. Adult C57BL/6 mice were used as the postnatal transplantation
      group. Donor cell levels in the peritoneum, peripheral blood, and various
      hematopoietic tissues were examined by flow cytometry. RESULTS: After fetal
      transplantation, peritoneal chimerism could be detected for 4 weeks, ranging from
      0.02 to 23.2 percent with the highest median chimerism at 2 weeks after
      transplantation. Donor cells in the peripheral blood, spleen, marrow, liver, and
      thymus were usually low (<0.2%) with a tendency for higher donor cell levels at 2
      weeks after transplantation. Engraftment in fetal peritoneum was primarily by
      myeloid and B cells with few T cells. In contrast, adult mice transplanted with
      haplogeneic marrow cleared nearly all donor cells from the peritoneum within a
      week of transplant. There was no evidence showing that donor cells had ever
      migrated to any hematopoietic tissues after adult transplantation. CONCLUSION:
      Despite limited engraftment in hematopoietic tissues, donor cells persisted in
      the peritoneum for 2 weeks or longer after fetal transplantation. The fetal
      peritoneum may serve as a sanctuary for foreign cells in the fetus, which may aid
      the development of novel cellular therapies for birth defects.

PMID- 18067494
TI  - Immunomagnetic selection of progenitor cells from peripheral blood after thawing
      with an automatic system in a pediatric patient with a neuroblastoma.
AB  - BACKGROUND: Immunomagnetic selection of peripheral blood progenitor cells (PBPCs)
      in patients with tumoral infiltration in marrow makes it possible to reduce
      contamination of cellular concentrates, but this procedure cannot always be used,
      mainly because of the low cellular count in apheresis concentrates. STUDY DESIGN
      AND METHODS: In this case two cellular concentrates taken separately at two
      different times were selected and cryopreserved; they were thawed with an
      automatic instrument. RESULTS: After manipulation, a selected concentrate
      containing 24.16 x 106 CD34+ cells with a purity of 90.15 percent was obtained;
      vitality after thawing and selection was 88 and 96 percent, respectively. The
      engraftment was achieved on Day +17 from the infusion of the previously selected
      PBPCs, as the literature also shows us. CONCLUSION: The time passed between the
      infusion and the engraftment gives us evidence of the efficacy of immunomagnetic
      selection carried out after thawing 2 cell units that were collected at different
      times from the same patient. In this way, it has been possible to perform an
      autologous transplant in a patient in which CD34+ cells transplant is
      recommended, but from whom the number of collected cells after a single
      mobilization cycle would not have been sufficient for the engraftment.

PMID- 18067495
TI  - Viability does not necessarily reflect the hematopoietic progenitor cell potency
      of a cord blood unit: results of an interlaboratory exercise.
AB  - BACKGROUND: Clinical transplant outcome with umbilical cord blood (UCB) as source
      of hematopoietic progenitor cells (HPCs) is, among other factors, determined by
      the total number of viable nucleated cells and/or CD34+ cells in the unit.
      Quantitative and qualitative losses by processing and cryopreservation and by
      thawing and washing before transfusion may occur, however. Another reason for a
      discrepancy between the number of cells in the unit released by the cord blood
      bank and found in the transplant center may be technical differences in cell
      counting methods between the two sites. STUDY DESIGN AND METHODS: With the
      collaborative group for Biomedical Excellence for Safer Transfusion (BEST), an
      interlaboratory exercise was conducted among nine sites for thawed UCB variables:
      total nucleated cells, CD34+ cells, viability, and HPC cultures. Three frozen UCB
      samples were shipped, with instructions for thawing, counting, and HPC plating.
      RESULTS: Unexpectedly samples arrived at all nine receiving centers without
      detectable hematopoietic progenitor colony-forming cells. Nevertheless, wide
      interlaboratory ranges for viability were obtained. The proportion of viable
      cells was found higher with manual methods, but all viability assays used in the
      study overestimated functional progenitor cells. CONCLUSIONS: The results
      underscore the complexity of evaluation of frozen-thawed cord blood cells and the
      need for standardization of assessment.

PMID- 18067496
TI  - A touch of TRALI.
AB  - Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion
      associated morbidity and mortality. The National Heart, Lung, and Blood Institute
      (NHLBI) and Canadian Consensus Conference definitions of TRALI exclude cases of
      mild TRALI. As a result, many cases of mild TRALI are likely to be missed. Three
      cases are reported in which patients experienced the acute onset of
      breathlessness in association with transfusion of blood components containing
      human leukocyte antigen (HLA) antibodies reactive with recipient HLA antigens.
      Despite the sudden onset of a pulmonary syndrome in association with transfusion,
      clinicians caring for these patients did not consider TRALI, and no case would
      meet recent consensus definitions. Nevertheless, supporting clinical and
      serologic evidence for TRALI was found in each case. Benefits in recognizing mild
      cases of TRALI include quantifying the true incidence of TRALI, understanding the
      physiology of mild versus severe TRALI, and preventing subsequent cases of TRALI
      due to donors found to have HLA antibodies.

PMID- 18067497
TI  - Evaluation of a new Trypanosoma cruzi antibody assay for blood donor screening.
AB  - BACKGROUND: This multicenter prospective study was designed to evaluate the
      performance characteristics of a new commercially available enzyme-linked
      immunosorbent assay (ELISA) for the detection of antibodies to Trypanosoma cruzi
      in blood donors, the ORTHO T. cruzi ELISA Test System (Ortho-Clinical
      Diagnostics). STUDY DESIGN AND METHODS: Assay specificity was evaluated among
      40,665 serum and ethylenediaminetetraacetate (EDTA) plasma specimens from
      volunteer blood donors and 481 T. cruzi antibody-negative specimens from a high
      risk population. Sensitivity was evaluated among 106 T. cruzi-infected subjects
      identified by parasite detection, among 93 radioimmunoprecipitation assay (RIPA)
      positive specimens from high-risk subjects, and 662 specimens presumed positive
      for the presence of T. cruzi antibodies by serologic methods. Also assessed were
      the equivalence of serum and plasma as specimen sources, performance equivalence
      of automated and semiautomated processing methods, nonspecific reactivity in
      specimens from other disease states or clinical conditions, and assay precision.
      RESULTS: Assay specificity was 99.998 percent in volunteer blood donors and 99.4
      percent among high-risk subjects. Sensitivity was 100 percent among specimens
      positive by parasite detection, or by serologic methods, and 98.9 percent among
      RIPA-positive specimens from high-risk subjects. No differences were demonstrated
      between serum and plasma or between semiautomated and automated processing
      methods. Cross-reactivity was observed with known positive leishmaniasis
      specimens. Total inter- and intraassay variability was less than 10 percent with
      both the automated and the semiautomated methods. CONCLUSION: The ORTHO T. cruzi
      ELISA Test System is an effective, qualitative assay for screening blood donors
      for immunoglobulin G antibodies to T. cruzi. The assay was licensed for donor
      screening by the FDA in December 2006.

PMID- 18067498
TI  - Enhancing attitudes and intentions in prospective blood donors: evaluation of a
      new donor recruitment brochure.
AB  - BACKGROUND: Although little empiric evidence has been published concerning the
      efficacy of blood donor recruitment materials, research suggests that simple
      attempts to enhance knowledge may not be sufficient to motivate donation. In
      contrast, recent donor motivation studies highlight the importance of anxiety,
      attitudes, and perceived ability to cope with donation (i.e., self-efficacy) as
      crucial determinants of donation intention. Therefore, recruitment materials that
      specifically address these constructs have the potential to outperform
      traditional educational brochures. STUDY DESIGN AND METHODS: Participants were
      randomly assigned to read one of three brochures: 1) a new brochure addressing
      common donor concerns and suggesting specific coping strategies, 2) a standard
      blood center brochure, or 3) a control brochure on healthy eating and exercise.
      Standardized questionnaires were completed before and after the brochures to
      assess change in blood donation anxiety, attitude, self-efficacy, and intention.
      RESULTS: Although no significant changes were noted for the control brochure,
      after reading the new brochure participants reported significant improvements in
      attitude, anxiety, self-efficacy, and donation intention. The standard donation
      brochure had an intermediate effect. CONCLUSION: Efforts to address common donor
      fears and to provide useful coping suggestions may improve the effectiveness of
      blood donation recruitment materials.

PMID- 18067499
TI  - Tranexamic acid reduces blood transfusion in total knee arthroplasty even when a
      blood conservation program is applied.
AB  - BACKGROUND: In total knee arthroplasty surgery, a blood conservation program is
      applied as a normal clinical practice to avoid allogenic transfusions. The
      objective of this study was to assess the effectiveness of tranexamic acid to
      reduce transfusions in total knee replacement even when a blood conservation
      program is applied. STUDY DESIGN AND METHODS: In a double-blind prospective study
      the patients scheduled for total knee arthroplasty were included in a well
      established blood conservation program and then randomly assigned into two
      groups: In tranexamic acid group, 10 mg per kg ev bolus followed by 1 mg per kg
      per hour perfusion was administered, while in the control group, saline was given
      matching the protocol. RESULTS: Ninety-five patients were included (tranexamic
      acid group, 46; control group, 49). Thirty-three patients (34.7%) underwent
      preoperative procedures to reduce transfusions: presurgical autologous blood
      donation (12), recombinant erythropoietin (6), and elementary iron (15);
      postoperative drain for reinfusion was allocated in all the cases. Total blood
      loss on the fourth postoperative day was [mean (+/-SD)] 1744 (+/-804) mL in
      controls compared with 1301 (+/-621) mL in the tranexamic acid group (p < 0.05).
      Eleven units of blood were transfused (6 patients) in the control group versus
      one in the tranexamic acid group (p < 0.05). Only 2 patients (4%) in the
      tranexamic acid group received reinfusion of blood recovered by drains compared
      with 36 (73%) in the control group (p < 0.0001). No thromboembolic complications
      were detected. CONCLUSION: Tranexamic acid reduces blood losses and transfusion
      requirements even when a blood conservation program was used and it questions the
      usefulness of the postoperative reinfusion drains.

PMID- 18067500
TI  - Is flow cytometry accurate enough to screen platelet autoantibodies?
AB  - BACKGROUND: The diagnosis of immune thrombocytopenic purpura (ITP) is a diagnosis
      of exclusion, as stated by international guidelines. Nevertheless, the assessment
      of platelet (PLT) antibodies has been reported as helpful for the diagnosis and
      the follow-up of ITP patients. PLT antibodies are detected by highly specialized
      assays, such as monoclonal antibody-specific immobilization of PLT antigen
      (MAIPA) test. Flow cytometry for PLT-associated immunoglobulin G (PAIgG)
      detection has been described more recently. This study was meant to evaluate the
      utility of flow cytometry to screen accurately patients needing further MAIPA
      testing. STUDY DESIGN AND METHODS: PAIgG, PAIgM, and PAIgA were determined in 107
      consecutive patients and in 147 healthy controls in parallel. MAIPA testing was
      performed in all patients. The accuracy of flow cytometry was assessed with a
      receiver operating characteristics (ROC) curve analysis versus MAIPA. RESULTS:
      MAIPA assay found PLT-specific IgG in 27 patients (25%). The ROC curve analysis
      showed that no false-negative result in flow cytometry was obtained for a mean
      fluorescence intensity (MFI) cutoff of 0.2. With this cutoff, PAIgG were positive
      in 61 patients (57%). In this series, MAIPA was unnecessary in 42 percent of
      patients (corresponding to true-negative results). When MAIPA was positive, PAIgM
      values ranged from 0.1 to 1.0, and PAIgA from 0.1 to 2. CONCLUSION: Flow
      cytometry for PAIgG assessment may be used to accurately decide whether or not
      MAIPA must be subsequently performed. In this series, MAIPA was unnecessary in 42
      percent of patients. Moreover, PAIgM results suggested that its determination
      combined with PAIgG may be of interest in ITP investigation.

PMID- 18067501
TI  - Blood group genotyping for Jk(a)/Jk(b), Fy(a)/Fy(b), S/s, K/k, Kp(a)/Kp(b),
      Js(a)/Js(b), Co(a)/Co(b), and Lu(a)/Lu(b) with microarray beads.
AB  - BACKGROUND: Traditionally, blood group typing has been performed with serologic
      techniques, the classical method being the hemagglutination test. Serotyping,
      however, may present important limitations such as scarce availability of rare
      antisera, typing of recently transfused patients, and those with a positive
      direct antiglobulin test. Consequently, serologic tests are being complemented
      with molecular methods. The aim of this study was to develop a low-cost, high
      throughput method for large-scale genotyping of red blood cells (RBCs). STUDY
      DESIGN AND METHODS: Single-nucleotide polymorphisms associated with some
      clinically important blood group antigens, as well as with certain rare blood
      antigens, were evaluated: Jk(a)/Jk(b), Fy(a)/Fy(b), S/s, K/k, Kp(a)/Kp(b),
      Js(a)/Js(b), Co(a)/Co(b), and Lu(a)/Lu(b). Polymerase chain reaction (PCR)
      amplified targets were detected by direct hybridization to microspheres coupled
      to allele-specific oligonucleotides. Cutoff values for each genotype were
      established with phenotyped and/or genotyped samples. RESULTS: The method was
      validated with a blind panel of 92 blood donor samples. The results were fully
      concordant with those provided by hemagglutination assays and/or sequence
      specific primer (SSP)-PCR. The method was subsequently evaluated with
      approximately 800 blood donor and patient samples. CONCLUSION: This study
      presents a flexible, quick, and economical method for complete genotyping of
      large donor cohorts for RBC alleles.

PMID- 18067502
TI  - ABO transcript levels in peripheral blood and erythropoietic culture show
      different allele-related patterns independent of the CBF/NF-Y enhancer motif and
      multiple novel allele-specific variations in the 5'- and 3'-noncoding regions.
AB  - BACKGROUND: Mechanisms regulating the ABO gene are unclear, especially in the
      hematopoietic compartment. The number of 43-bp repeats in the CBF/NF-Y-binding
      enhancer region is considered to have a major influence on transcription. STUDY
      DESIGN AND METHODS: Transcript levels in peripheral blood and in erythropoietic
      culture of CD34+ cells from marrow donors were measured with TaqMan assays. The
      5'-regulatory region and 3'-downstream sequences were investigated to determine
      if allelic variations occur. RESULTS: Surprisingly, transcripts from A(1) and
      A(2) alleles could not be detected in peripheral blood, although transcripts from
      B/O(1)/O(1v)/O(2) alleles were readily observed. Sequencing of approximately 4 kb
      upstream and 1.8 kb downstream of the coding region showed multiple novel allele
      specific and allele-related motifs. No correlation between these sequence
      variations and transcript levels was found, however. Contradictory to the results
      with peripheral blood, in erythropoietic culture of CD34+ cells from healthy
      marrow donors transcripts from A(1) and A(2) alleles were found at higher levels
      than transcripts from B/O(1)/O(1v) alleles. CONCLUSION: These data do not support
      previous suggestions that nonsense-mutated O(1)/O(1v) transcripts are eliminated
      first. Furthermore, our results contradict the notion that the number of repeats
      in the upstream CBF/NF-Y-binding enhancer region, which contains four 43-bp
      repeats in A(2)/B/O(1)/O(1v) but only one 43-bp unit in A(1)/O(2) alleles,
      determines the transcription rate. The reason for the remarkable discrepancy
      between blood and marrow remains to be elucidated.

PMID- 18067503
TI  - Sec1-FUT2-Sec1 hybrid allele generated by interlocus gene conversion.
AB  - BACKGROUND: Many single-nucleotide polymorphisms have been identified in the
      coding region of the FUT2 locus, which encodes secretor type
      alpha(1,2)fucosyltransferase. In addition, three recombination alleles have been
      reported. Of these recombination alleles, a fusion gene generated by an unequal
      crossing over between Sec1, a pseudogene that locates 23 kb upstream to and has
      high sequence homology with FUT2 and FUT2, was identified as a Japanese-specific
      nonsecretor allele (se(fus)). STUDY DESIGN AND METHODS: During the screening of
      the se(fus) in Mongolians (n = 118), a hybrid allele of Sec1-FUT2-Sec1 was found.
      RESULTS: The DNA sequence suggested that the Sec1-FUT2-Sec1 allele contains a 275
      bp sequence (between positions 259 and 533) that is identical to the FUT2
      sequence including a 54-bp FUT2-specific region (between positions 417 and 470)
      and that might have been generated by an interlocus gene conversion. CONCLUSION:
      Because the recombination region of se(fus) and the upstream recombination region
      of Sec1-FUT2-Sec1 are almost identical, this sequence stretch is likely to be the
      breakpoint for different kinds of recombinations that occur in this family of
      genes.

PMID- 18067504
TI  - Expression of a novel missense mutation found in the A4GALT gene of Amish
      individuals with the p phenotype.
AB  - BACKGROUND: The rare p phenotype is found at a higher frequency in Amish people
      than in other populations. Different mutations in the 4-alpha
      galactosyltransferase gene (A4GALT), responsible for synthesis of P(k) (Gb(3))
      antigen, have been found to cause the P(k)-deficient p phenotype. The aim of this
      study was to explore the molecular background of the p phenotype in people of
      Amish origin. STUDY DESIGN AND METHODS: Twenty blood samples with the p
      phenotype, 19 of them from Amish individuals and 1 Pakistani, were investigated.
      Amplification of genomic DNA by polymerase chain reaction (PCR) and sequencing by
      capillary electrophoresis were performed. Blood donors of different geographic
      origin were screened with PCR-allele-specific primer to investigate whether the
      novel mutation occurs among individuals with common phenotypes. The mutation was
      also cloned into an expression vector and transfected to Namalwa cells, which do
      not normally express P(k). P(k) expression on the transfected cells and P/P(k) on
      red blood cells (RBCs), both with p and with common phenotypes, were analyzed by
      flow cytometry. RESULTS: All 20 samples were homozygous for 299C>T changing
      serine to leucine in a region that is highly conserved in homologous genes across
      species borders. The mutation was not found in any of the 500 alleles of blood
      donors investigated. P(k) expression was neither observed by serology and flow
      cytometry on p RBCs from Amish individuals nor following transfection of cells
      with constructs containing the novel missense mutation. CONCLUSION: A novel
      A4GALT missense mutation causes the p phenotype in Amish individuals.

PMID- 18067505
TI  - Rh discrepancies caused by variable reactivity of partial and weak D types with
      different serologic techniques.
AB  - BACKGROUND: RhD discrepancies between current and historical results are
      problematic to resolve. The investigation of 10 discrepancies is reported here.
      STUDY DESIGN: Samples identified were those that reacted by automated gel
      technology and were negative with an FDA-approved reagent. Reactivity with a
      commercially available panel of monoclonal anti-D was performed. Genomic DNA was
      evaluated for RHD alleles with multiplex RHD exon polymerase chain reaction
      (PCR), weak D PCR-restriction fragment length polymorphism, and RHD exon 5 and 7
      sequence analyses. RESULTS: The monoclonal anti-D panel identified two samples as
      DVa, yet possessed the DAR allele. Two weak D Type 1 samples had a similar
      monoclonal anti-D profile, but only one reacted directly with one of two FDA
      approved anti-D. Only two of four weak D Type 2 samples reacted directly with one
      FDA-approved anti-D, and their D epitope profile differed. CONCLUSIONS: The
      monoclonal anti-D reagents did not distinguish between partial and weak D Types 1
      and 2. Weak D Types 1 and 2 do not show consistent reactivity with FDA-approved
      reagents and technology. To limit anti-D alloimmunization, it is recommended that
      samples yielding an immediate-spin tube test cutoff score of not more than 5
      (i.e., < or =1+ agglutination) or a score of not more than 8 (i.e., < or =2+
      hemagglutination) by gel technology be considered D- for transfusion and Rh
      immune globulin prophylaxis. That tube test anti-D reagents react poorly with
      some Weak D Types 1 and 2 red cells is problematic, inasmuch as they should be
      considered D+ for transfusion and prenatal care. Molecular tests that distinguish
      common partial and Weak D types provide the solution to resolving D antigen
      discrepancies.

PMID- 18067506
TI  - Heterogeneity of HPA-3 alloantibodies: consequences for the diagnosis of
      alloimmune thrombocytopenic syndromes.
AB  - BACKGROUND: Immunization against the human platelet alloantigen (HPA)-3a residing
      on alphaIIbbeta3 integrin accounts for approximately 2 percent of fetal and
      neonatal alloimmune thrombocytopenia (FNAIT). Anti-HPA-3a alloantibodies are
      sometimes difficult to detect and can be overlooked by standard antigen capture
      assays. STUDY DESIGN AND METHODS: The reactivity of 12 anti-HPA-3a and 2 anti-HPA
      3b alloantibodies from patients with FNAIT and posttransfusion purpura was
      analyzed by serologic (monoclonal antibody-specific immobilization of platelet
      antigens [MAIPA] assay, flow cytometry) and immunochemical (immunoprecipitation,
      immunoblotting) techniques. The influence of platelet (PLT) age, storage
      conditions, recombinant antigens from Chinese hamster ovary (CHO) cells, and
      sialic acids (treatment with neuraminidase) were analyzed. RESULTS: The most
      sensitive anti-HPA-3 alloantibody detection in MAIPA assay could be achieved with
      fresh homozygous PLTs. During a PLT storage period of 14 days before use, three
      types of anti-HPA-3 alloantibodies were found: 1) complete loss of reactivity (n
      = 6), 2) considerably weakened reaction (> or =50% reduction; n = 3), and 3)
      minor reduction of reactivity (< or =40% decrease; n = 5). When cryopreserved
      PLTs were used, 10 of 12 anti-HPA-3a and all anti-HPA-3b alloantibodies reacted
      positive. Only 6 of 10 serum samples reacted with recombinant HPA-3a on CHO
      cells. Neuraminidase treatment of PLTs showed that some anti-HPA-3a
      alloantibodies require the presence of sialic acids. The storage lesion seems to
      be related to cleavage of sialic acids. Immunochemical analysis revealed evidence
      that most anti-HPA-3a alloantibodies require an intact three-dimensional
      alphaIIbbeta3 integrin structure. CONCLUSIONS: Anti-HPA-3 alloantibodies show
      considerable heterogeneity, which may hamper the serologic diagnosis of FNAIT.
      Preservation of the alphaIIbbeta3 integrin and protection from enzymatic
      degradation seem to be important during PLT storage.

PMID- 18067507
TI  - Vesicles generated during storage of red cells are rich in the lipid raft marker
      stomatin.
AB  - BACKGROUND: The release of vesicles by red blood cells (RBCs) occurs in vivo and
      in vitro under various conditions. Vesiculation also takes place during RBC
      storage and results in the accumulation of vesicles in RBC units. The membrane
      protein composition of the storage-associated vesicles has not been studied in
      detail. The characterization of the vesicular membrane might hint at the
      underlying mechanism of the storage-associated changes in general and the
      vesiculation process in particular. STUDY DESIGN AND METHODS: Vesicles from RBCs
      that had been stored for various periods were isolated and RBCs of the same RBC
      units were used to generate calcium-induced microvesicles. These two vesicle
      types were compared with respect to their size with atomic force microscopy,
      their raft protein content with detergent-resistant membrane (DRM) analysis, and
      their thrombogenic potential and activity with annexin V binding and thrombin
      generation, respectively. RESULTS: The storage-associated vesicles and the
      calcium-induced microvesicles are similar in size, in thrombogenic activity, and
      in membrane protein composition. The major differences were the relative
      concentrations of the major integral DRM proteins. In storage-associated
      vesicles, stomatin is twofold enriched and flotillin-2 is threefold depleted.
      CONCLUSION: These data indicate that a stomatin-specific, raft-based process is
      involved in storage-associated vesiculation. A model of the vesiculation process
      in RBCs is proposed considering the raft-stabilizing properties of stomatin, the
      low storage temperature favoring raft aggregation, and the previously reported
      storage-associated changes in the cytoskeletal organization.

PMID- 18067508
TI  - Effects of high-yield thrombocytapheresis on the quality of platelet products.
AB  - BACKGROUND: The steadily increasing demands for single-donor apheresis platelet
      (PLT) concentrates (APCs) are a challenge to the PLT supply system. Therefore,
      efforts to improve plateletpheresis yield, allowing apheresis products to be
      split into 2 or more units, are valuable strategies. No data to demonstrate in
      vivo transfusion efficacy of these high-yield split-APCs are currently available,
      however. STUDY DESIGN AND METHODS: The transfusion efficacy of APCs produced by
      two apheresis methods involving different harvest and storing procedures and
      varying PLT yields was investigated. Efficacy measures were the 1-hour percent
      PLT recovery (PPR(1h)) and the 1-hour corrected count increment (CCI(1h)). In
      total, 400 APCs, produced with either an Amicus device (Baxter) and stored in PLT
      additive solution (T-Sol; Amicus method [AM], n = 107) or a Trima device (Gambro)
      and stored in plasma (Trima method [TM], n = 293), were transfused to 55 children
      (31 girls; median age, 9.5 years; range, 0.2-18.5 years) with thrombocytopenia
      due to chemotherapy or aplastic anemia (median, 4 APCs per child; range, 1-68).
      RESULTS: Transfusion efficacy was significantly lower for AM-APCs than for TM
      APCs (median PPR(1h), 17 and 33%; median CCI(1h), 7.9 and 15.6, respectively; p <
      0.001). Reduced transfusion efficacy correlated in a yield-dependent manner with
      high apheresis PLT yields (> or =6 x 10(11)) for AM-APCs (p < 0.001). CONCLUSION:
      Although in vitro validation of AM- and TM-APCs has been performed, only by
      evaluating transfusion efficacy in vivo did the AM turn out to be not suitable
      for high-yield thrombocytapheresis. This study recommends the implementation of
      in vivo transfusion efficacy studies for high-yield APC apheresis donations.

PMID- 18067509
TI  - Red cell concentrates of hemochromatosis patients comply with the storage
      guidelines for transfusion purposes.
AB  - BACKGROUND: Therapeutic phlebotomy is the preferred treatment for iron overload
      associated with hemochromatosis. In the Netherlands, red blood cell concentrates
      (RCCs) from hemochromatosis patients are not used for transfusion purposes. In
      this study, their storage performance was compared with that of control donors as
      a first step in the evaluation of their potential usefulness for transfusion.
      STUDY DESIGN AND METHODS: RCCs were obtained from hemochromatosis patients and
      regular donors, either by apheresis or by whole-blood collection, and stored up
      to 50 days under routine Dutch blood bank conditions. Weekly samples were taken
      for determination of hematologic, biophysical, and biochemical variables.
      RESULTS: Most variables displayed the same storage-related changes in RCCs
      originating from hemochromatosis patients as in those from regular donors. In all
      RCCs, hemolysis remained well below the guideline limit of 0.8 percent for up to
      6 weeks of storage, and the glucose concentration remained above the required 5
      mmol per L up to 5 weeks of storage. After 4 weeks of storage, the mean ATP level
      remained above the required limit of 75 percent of the starting value in all RCCs
      as well. The major difference was a larger mean cell volume in hereditary
      hemochromatosis RBCs up to 50 days of storage. CONCLUSIONS: RCCs from
      hemochromatosis patients comply with the in vitro quality requirements for
      transfusion. This paves the way for the final step, namely, the establishment of
      the 24-hour RBC posttransfusion recovery.

PMID- 18067510
TI  - Comprehensive proteomic analysis of protein changes during platelet storage
      requires complementary proteomic approaches.
AB  - BACKGROUND: Proteomics methods may be used to analyze changes occurring in stored
      blood products. These data sets can identify processes leading to storage
      associated losses of blood component quality such as the platelet (PLT) storage
      lesion (PSL). The optimal strategy to perform such analyses to obtain the most
      informative data sets, including which proteomics methods, is undefined. This
      study addresses relative differences among proteomics approaches to the analysis
      of the PLT storage lesion. STUDY DESIGN AND METHODS: Changes to the PLT proteome
      between Days 1 and 7 of storage were analyzed with three complementary proteomic
      approaches with final mass spectrometry analysis: two-dimensional (2D) gel
      electrophoresis/differential gel electrophoresis (DIGE), isotope tagging for
      relative and absolute quantitation (iTRAQ), and isotope-coded affinity tagging
      (ICAT). Observed changes in concentration during storage of selected proteins
      were confirmed by immunoblotting. RESULTS: In total, 503 individual proteins
      changed concentration over a 7-day storage period. By method, a total of 93
      proteins were identified by 2D gel/DIGE, 355 by iTRAQ, and 139 by ICAT. Less than
      16 percent of the 503 proteins, however, were identified by not more than at
      least two proteomic approaches. Only 5 proteins were identified by all
      approaches. Membrane protein changes were not reliably detected with 2D gel/DIGE
      methods. CONCLUSION: Although proteomics analyses identified many storage
      associated protein changes, these varied significantly by method suggesting that
      a combination of protein-centric (2D gel or DIGE) and peptide-centric (iTRAQ or
      ICAT) approaches are essential to acquire adequate data. The use of one
      proteomics method to study changes in stored blood products may give insufficient
      information.

PMID- 18067511
TI  - Electronic remote blood issue: a combination of remote blood issue with a system
      for end-to-end electronic control of transfusion to provide a "total solution"
      for a safe and timely hospital blood transfusion service.
AB  - BACKGROUND: The rapid provision of red cell (RBC) units to patients needing blood
      urgently is an issue of major importance in transfusion medicine. The development
      of electronic issue (sometimes termed "electronic crossmatch") has facilitated
      rapid provision of RBC units by avoidance of the serologic crossmatch in eligible
      patients. A further development is the issue of blood under electronic control at
      blood refrigerator remote from the blood bank. STUDY DESIGN AND METHODS: This
      study evaluated a system for electronic remote blood issue (ERBI) developed as an
      enhancement of a system for end-to-end electronic control of hospital
      transfusion. Practice was evaluated before and after its introduction in cardiac
      surgery. RESULTS: Before the implementation of ERBI, the median time to deliver
      urgently required RBC units to the patient was 24 minutes. After its
      implementation, RBC units were obtained from the nearby blood refrigerator in a
      median time of 59 seconds (range, 30 sec to 2 min). The study also found that
      unused requests were reduced significantly from 42 to 20 percent, the number of
      RBC units issued reduced by 52 percent, the number of issued units that were
      transfused increased from 40 to 62 percent, and there was a significant reduction
      in the workload of both blood bank and clinical staff. CONCLUSIONS: This study
      evaluated a combination of remote blood issue with an end-to-end electronically
      controlled hospital transfusion process, ERBI. ERBI reduced the time to make
      blood available for surgical patients and improved the efficiency of hospital
      transfusion.

PMID- 18067513
TI  - The estimated number of patients with adult congenital heart defects in Norway.
AB  - An increasing survival rate for adult patients with congenital heart defects has
      been related to increased hospitalization and a greater risk of incidences during
      physical activity. The limited follow-up of these adult patients is partly due to
      a lack of knowledge about the number of adult patients in need of specialized
      care. Based on a classification into simple, moderate and severe forms of
      congenital heart defect, the population size was estimated for three age
      categories. Based on a conservative prevalence at birth of 7.0 per 1000 live
      births, approximately 14,000 adult patients with congenital heart defects between
      16 and 64 years are alive in Norway today and in need of specialized cardiology
      attention. This is almost twice the number of children with a congenital heart
      defect. The assessment of the number of patients is important in order to reveal
      the risks of fatal incidence during physical activity in the adult congenital
      heart disease group. There is a need for knowledge and education about the
      potential risks during sports in coaches, teachers, health personnel, employers,
      parents, caretakers and in the patients themselves.

PMID- 18067512
TI  - Increased versican content is associated with tendinosis pathology in the
      patellar tendon of athletes with jumper's knee.
AB  - Expansion of the extracellular matrix is a prominent but poorly characterized
      feature of tendinosis. The present study aimed to characterize the extent and
      distribution of the large aggregating proteoglycan versican in patients with
      patellar tendinosis. We obtained tendon from tendinopathy patients undergoing
      debridement of the patellar tendon and from controls undergoing intramedullary
      tibial nailing. Versican content was investigated by Western blotting and
      immunohistochemistry. Microvessel thickness and density were determined using
      computer-assisted image analysis. Markers for smooth muscle actin, endothelial
      cells (CD31) and proliferating cells (Ki67) were examined immunohistochemically.
      Western blot analysis and immunohistochemical staining revealed elevated versican
      content in the proximal patellar tendon of tendinosis patients (P=0.042).
      Versican content was enriched in regions of fibrocartilage metaplasia and
      fibroblast proliferation, as well as in the perivascular matrix of proliferating
      microvessels and within the media and intima of arterioles. Microvessel density
      was higher in tendinosis tissue compared with control tissue. Versican deposition
      is a prominent feature of patellar tendinosis. Because this molecule is not only
      a component of normal fibrocartilagenous matrices but also implicated in a
      variety of soft tissue pathologies, future studies should further detail both
      pathological and adaptive roles of versican in tendons.

PMID- 18067514
TI  - Patellar tendon shortening after treatment of patellar instability with a
      patellar tendon medialization procedure.
AB  - Patellar instability is a multifactorial disorder. Patella alta is strongly
      associated with patellar instability. We hypothesize that procedures of the
      patellar tendon such as medialization may shorten the patellar tendon. In this
      retrospective study, 41 patients with patellar instability were treated
      operatively with a patellar tendon medialization procedure. Twenty-eight knees
      were treated using a modified Roux-Goldthwait method and 16 using a modified
      Elmslie-Trillat method. The patients were followed 2-7 years after the operation.
      Pre- and post-operative x-rays were analyzed with particular emphasis on patellar
      tendon length, patellofemoral congruence angle and osteoarthritis. The final
      clinical outcome was assessed using the Lysholm score and clinical examination.
      In both groups patients were generally satisfied with the result of the operation
      and there was no significant difference in Lysholm scores at follow-up. However,
      patellofemoral osteoarthritic changes increased in both groups compared with the
      pre-operative status. The patellar tendon length was reduced in both groups, but
      significantly, by 7%, in the Roux-Goldthwait group. We conclude that patellar
      tendon shortens after a Roux-Goldthwait procedure.

PMID- 18067515
TI  - Cycling to work: influence on indexes of health in untrained men and women in
      Flanders. Coronary heart disease and quality of life.
AB  - The purpose of this study was to examine if a 1-year lifestyle intervention study
      (cycling to work) has an influence on coronary heart disease (CHD) risk factors
      and health-related quality of life, in previously untrained healthy adults.
      Healthy, untrained men and women, who did not cycle to work, participated in an
      intervention study. Sixty-five subjects (intervention group: IG) were asked to
      cycle to work at least 3 times a week and 15 controls (CG) were asked not to
      change their living habits. All measurements were performed on 3 consecutive
      occasions, with 6 months in between. Physical performance, venous blood samples,
      blood pressure (BP), and the SF-36 Health Status Survey were assessed. Cycling
      characteristics and leisure-time physical activities were reported in a dairy.
      Total cholesterol (TC), LDL, TC/HDL and diastolic BP decreased and HDL increased
      significantly in the IG. TC and LDL decreased significantly in the CG. Vitality
      for the total group and physical functioning for women significantly changed over
      time between IG and CG in the first 6 months. These results show that cycling to
      work has a positive influence on CHD risk factors and is likely to improve the
      health-related quality of life in previously untrained healthy adults.

PMID- 18067516
TI  - Post-exercise heart rate variability of endurance athletes after different high
      intensity exercise interventions.
AB  - Methodological problems have limited the number of studies on heart rate
      variability (HRV) dynamics immediately after exercise. We used the short-time
      Fourier transform method to study immediate (5 min) and slow (30 min) recovery of
      HRV after different high-intensity exercise interventions. Eight male athletes
      performed two interval interventions at 85% and 93% (IV(85) and IV(93)) and two
      continuous interventions at 80% and 85% (CO(80) and CO(85)) of the velocity at
      VO2max (vVO2max). We found no increase in high frequency power (HFP), but low
      frequency (LFP) and total power (TP) increased (P<0.05) during the first 5 min of
      the recovery after each intervention. During the 30-min recovery, HFP, LFP and TP
      (1) increased slowly toward resting values, but HFP remained lower (P<0.01) than
      at rest, (2) were lower (P<0.05) after IV(93) and CO(85) when compared with
      IV(85) and CO(80), respectively and (3) were lower (P<0.01) after CO(85) when
      compared with IV(85). HRV recovery was detected during the immediate recovery
      after interventions. Increased exercise intensity resulted in lower HRV both in
      interval and in continuous interventions. In addition, when interval and
      continuous interventions were performed at a similar workload, HRV was lower
      after continuous intervention.

PMID- 18067517
TI  - Physical activity counteracts increased whole-body protein breakdown in chronic
      obstructive pulmonary disease patients.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with increased whole
      body protein breakdown and low-grade systemic inflammation. We aimed to determine
      if physical training of patients with COPD induces anti-inflammatory effects and
      decreases whole-body protein breakdown. Nineteen subjects with severe
      (FEV(1)=31+/-1) COPD were randomized into a training group (n=9) and a control
      group (n=10). Twenty healthy subjects were studied for baseline comparison. The
      "COPD training" group participated in an outpatient rehabilitation program
      consisting of endurance training (walking at 85% of VO(2max)) twice weekly for 7
      weeks plus daily home-based training. Maximum walking distance increased by
      almost 70% in the training group after 7 weeks of training. At baseline, the
      concentrations of C-reactive protein (CRP) and IL-18 in plasma were increased in
      subjects with COPD compared with healthy subjects (P<0.05) and leucine rate of
      appearance (R(a)) was approximately 15% greater (P<0.05) in subjects with COPD.
      Training had no effect on the plasma concentration of inflammatory markers but
      decreased leucine R(a) in subjects with COPD by approximately 10% (P<0.05). In
      conclusion, 7 weeks of physical training markedly improved endurance in patients
      with COPD and accelerated whole-body protein breakdown in patients with COPD was
      attenuated by physical training independent of changes in inflammatory markers.

PMID- 18067518
TI  - Influence of pacing strategy on O2 uptake and exercise tolerance.
AB  - Seven male subjects completed cycle exercise bouts to the limit of tolerance on
      three occasions: (1) at a constant work rate (340+/-57 W; even-pace strategy;
      ES); (2) at a work rate that was initially 10% lower than that in the ES trial
      but which then increased with time such that it was 10% above that in the ES
      trial after 120 s of exercise (slow-start strategy; SS); and, (3) at a work rate
      that was initially 10% higher than that in the ES trial but which then decreased
      with time such that it was 10% below that in the ES trial after 120 s of exercise
      (fast-start strategy; FS). The expected time to exhaustion predicted from the pre
      established power-time relationship was 120 s in all three conditions. However,
      the time to exhaustion was significantly greater (P<0.05) for the FS (174+/-56 s)
      compared with the ES (128+/-21 s) and SS (128+/-30 s) conditions. In the FS
      condition, (.)VO2 increased more rapidly toward its peak such that the total O2
      consumed in the first 120 s of exercise was greater (ES: 5.15+/-0.78; SS: 5.07+/
      0.83; FS: 5.36+/-0.84 L; P<0.05 for FS vs ES and SS). These results suggest that
      a fast-start pacing strategy might enhance exercise tolerance by increasing the
      oxidative contribution to energy turnover and hence "sparing" some of the finite
      anaerobic capacity across the transition to high-intensity exercise.

PMID- 18067519
TI  - Social physique anxiety and sociocultural attitudes toward appearance impact on
      orthorexia test in fitness participants.
AB  - This study investigates how scores on the Social Physique Anxiety Scale (SPAS)
      and the Sociocultural Attitudes Towards Appearance Questionnaire (SATAQ) relate
      to Bratman's orthorexia test (BOT) scores with regard to age, sex, and self
      reported exercise frequency and duration in a sample of Swedish participants in
      fitness center activities. A total of 251 participants (166 women and 85 men)
      completed the SPAS, the SATAQ, and a questionnaire focusing on exercise frequency
      and duration. The results indicated that the SATAQ subdomain internalization
      could itself explain the variation in BOT results. In women, the results
      indicated that exercise frequency, followed by SPAS score and the SATAQ
      subdomains internalization and awareness, could together explain the variation in
      BOT results. Fitness centers could make a point of emphasizing that some physical
      ideals are neither healthy nor realistic, thus strengthening member self-image
      and preventing social physique anxiety, eating disorders, and negative attitudes
      toward appearance.

PMID- 18067520
TI  - Morphological comparison of different protocols of skeletal muscle remobilization
      in rats after hindlimb suspension.
AB  - The aim of this study was to evaluate and compare the efficacy of different
      remobilization protocols in different skeletal muscles considering the changes
      induced by hindlimb suspension of the tail. Thirty-six female Wistar rats were
      divided into six groups: control I, control II, suspended, suspended free,
      suspended trained on a declined treadmill and suspended trained on a flat
      treadmill. Fragments of soleus and tibialis anterior (TA) muscle were frozen and
      processed by different histochemical methods. The suspended soleus showed a
      significant increase in the proportional number of intermediate/hybrid fibers and
      a decrease in the number of type I fibers. Some of these changes proved to be
      reversible after remobilization. The three remobilization programs led to the
      recovery of both the proportional number of fibers and their size. The TA muscle
      presented a significant increase in the number and size of type I fibers and a
      cell size reduction of type IIB fibers, which were recovered after training on a
      declined treadmill and free movement. Especially regarding the soleus, the
      present findings indicate that, among the protocols, training on a declined
      treadmill was found to induce changes of a more regenerative nature, seemingly
      indicating a better tissue restructuring after the suspension procedure.

PMID- 18067521
TI  - Endothelial nitric oxide synthase gene polymorphism and elite endurance athlete
      status: the Genathlete study.
AB  - In the Genathlete study, we examined the contribution of three polymorphisms in
      the endothelial nitric oxide synthase (NOS3) gene to discriminate elite endurance
      athletes (EEA) from sedentary controls (SC). The EEA group included a total of
      316 Caucasian males with a VO2max >75 mL/kg. The SC group comprised 299 unrelated
      sedentary Caucasian males who had VO2max values below 50 mL/kg. The polymerase
      chain reaction technique was used to amplify a microsatellite (CA)(n) repeat in
      intron 13, a 27 bp repeat in intron 4 and a third fragment in exon 7 containing
      the Glu298Asp SNP. No difference was found between the EEA and SC groups for the
      27 bp repeat and the Glu298Asp polymorphism. Chi-square analysis of the overall
      allelic distribution of the (CA)(n) repeat revealed no significant difference
      between the two groups (P=0.135). However, comparing carriers and non-carriers
      for the most common (CA)(n) repeat alleles, we found significant differences
      between SC and EEA, with more EEA subjects carrying the 164 bp allele (P=0.007).
      In summary, we found suggestive evidence that the 164 bp allele of the (CA)(n)
      repeat in intron 13 is associated with EEA status and may account for some of the
      differences between EEA and SC.

PMID- 18067522
TI  - A comparison of pediatric freestyle and Greco-Roman wrestling injuries sustained
      during a 2006 US national tournament.
AB  - The purpose of this study was to compare the epidemiology of freestyle and Greco
      Roman wrestling injuries sustained during a 2006 United States (US) national
      tournament. A prospective injury surveillance study was conducted at the US 2006
      ASICS/Vaughan Cadet and Junior National Championships. There were 83 freestyle-
      and 55 Greco-Roman-related injuries sustained, with the rate of injury per 1000
      athlete-matches higher in freestyle (7.0) compared with Greco-Roman (4.6)
      wrestling [Rate ratio (RR)=1.51, 95% confidence interval (CI): 1.07-2.12].
      Compared with Greco-Roman wrestling, there was a greater proportion of knee
      injuries in freestyle wrestling [injury proportion ratio (IPR)=4.17, 95% CI: 1.30
      13.41]. In GrecoRoman wrestling, there were greater proportions of elbow
      (IPR=9.11, 95% CI: 1.13-73.59) and head/face/neck (IPR=1.72, 95% CI: 1.10-2.67)
      injuries and a greater proportion of concussions (IPR=1.95, 95% CI: 0.92-4.12),
      although the latter was statistically insignificant. Greco-Roman wrestlers
      sustained a greater proportion of injuries from being driven into the mat
      (IPR=2.97, 95% CI: 1.72-5.14). There were no statistically significant
      differences in injury outcome by wrestling style. The differing injury rates and
      patterns of injury between freestyle and Greco-Roman wrestling are likely due to
      the different rules between these styles that allow lower leg attacks in
      freestyle wrestling and encourage the use of throws in Greco-Roman wrestling.

PMID- 18067523
TI  - Effects of eccentric cycling exercise on IGF-I splice variant expression in the
      muscles of young and elderly people.
AB  - Recovery from micro damage resulting from intensive exercise has been shown to
      take longer in older muscles. To investigate the factors that may contribute to
      muscle repair, we have studied the expression of two splice variants of the
      insulin-like growth factor-I (IGF-I) gene. IGF-IEa and mechano growth factor
      (MGF) were studied in response to 1 h of eccentric cycling exercise in young and
      old individuals. Subjects (nine young, aged 20-27 years and eight elderly, aged
      67-75 years) completed an eccentric exercise protocol that consisted of 60 min of
      reverse pedal cycling. Workloads were chosen to give the same relative increases
      in oxygen uptake (VO2max) and heart rate in young and old subjects. Muscle biopsy
      samples were obtained from the quadriceps muscle before and 2 1/4 h after
      completion of the exercise bout and were analyzed for IGF-IEa and MGF mRNA levels
      using real-time quantitative PCR. No difference was observed between the baseline
      levels of the two splice variants between the two subject groups. Eccentric
      cycling exercise resulted in a significant increase in the mean MGF mRNA in both
      young and old subjects but did not alter IGF-IEa mRNA levels in either age group.
      As reported previously (Toft et al., 2002), the levels of serum creatine kinase
      and myoglobin, markers of muscle damage, were increased significantly from
      baseline and to 5 days after exercise in both young and old subjects. This
      supports previous research in suggesting that the MGF splice variant is sensitive
      to muscle damage-inducing exercise and is differentially regulated compared with
      IGF-IEa.

PMID- 18067524
TI  - Effect of eight weeks of endurance exercise training on right and left
      ventricular volume and mass in untrained obese subjects: a longitudinal MRI
      study.
AB  - The aim of the present investigation was to examine how 8 weeks of intense
      endurance training influenced right and left ventricular volumes and mass in
      obese untrained subjects. Ten overweight subjects (19-47 years; body mass index
      of 34+/-5 kg/m(2)) underwent intensive endurance training (rowing) three times 30
      min/week for 8 weeks at a relative intensity of 72+/-8% of their maximal heart
      rate response (mean+/-SD). Before and after 8 weeks of endurance training, the
      left and the right end-diastolic volume (EDV), end-systolic volume (ESV),
      ejection fraction (EF), stroke volume (SV) and ventricular mass (VM) were
      measured by Magnetic resonance imaging (MRI). Submaximal heart rate decreased
      from 126+/-5 to 113+/-3 b.p.m. (10%; P<0.01), and from 155+/-5 to 141+/-4 b.p.m.
      (9%; P<0.001) at submaximal workloads of 70 and 140 W (110 W for women),
      respectively (mean+/-SEM). Resting ventricular parameters increased
      significantly: left ventricular SV, EDV and VM increased by 6%, 7% and 13%,
      respectively (P<0.01). The right side of the heart showed significant changes in
      SV, EDV and VM with increase of 4%, 4% and 12%, respectively (P<0.05). Eight
      weeks of endurance training significantly increased left ventricular SV and right
      ventricular SV, due to an increase in left ventricular EDV and right ventricular
      EDV. Furthermore, left VM and right VM increased. We conclude that using MRI and
      a longitudinal design it was possible to demonstrate similar and balanced changes
      in the right and left ventricle in response to training.

PMID- 18067525
TI  - Changed cortical activity after anterior cruciate ligament reconstruction in a
      joint position paradigm: an EEG study.
AB  - After reconstruction of the anterior cruciate ligament (ACL) afferent
      proprioceptive information from the knee joint may be altered. In order to
      examine changes in central activation patterns, spectral features of the
      electroencephalography (EEG) were measured. Patients after ACL reconstruction and
      healthy controls carried out an knee-angle reproduction task in a groups x limbs
      x trials design. Cortical activity was recorded using international standards.
      FFT were conducted to determine power at Theta, Alpha-1, Alpha-2 and Beta-1.
      Statistics show significantly larger aberrations in the reconstructed limbs
      compared with the controls whereas there are no differences between the
      uninvolved land controls. Brain activity demonstrates significantly higher
      frontal Theta-power (F3, F4, F8) in both limbs of the ACL group vs the controls
      and a significantly higher Alpha-2 power was shown in the ACL-reconstructed limb
      compared with controls at parietal positions (P3, P4). No such differences were
      found between the uninvolved side and the controls. The EEG was able to measure a
      change in joint position sense at the cortical level after the reconstruction of
      the ACL. The results of these findings might indicate differences in focused
      attention with involvement of the anterior cingulate cortex (frontal Theta) and
      sensory processing in the parietal somatosensory cortex (Alpha-2).

PMID- 18067526
TI  - Rehabilitation and recovery after anterior cruciate ligament reconstruction:
      patients' experiences.
AB  - The aim was to explore patients' experiences of the rehabilitation process after
      anterior cruciate ligament (ACL) reconstruction. Ten participants were enrolled
      in the study. Semi-structured interviews were performed, focusing on challenges
      during the post-operative rehabilitation to 1 year after ACL reconstruction. The
      participants perceived no real choice between operative and non-operative
      treatment. Only surgery symbolized a full return to the pre-injury level of
      sports, and surgery was understood as the only way to become a completely
      restored "functional human being." A major source of frustration was that the
      meaning of and progress during the rehabilitation did not match their
      expectations. Three different responses to the challenge of a prolonged
      rehabilitation were expressed: "going for it,""being ambivalent," and "giving
      in." Fear of re-injury was common; however, some participants decided not to
      return to their pre-injury level of sports due to reasons other than physical
      limitations or fear of re-injury. From a patient perspective, it seems important
      that the choice of operative or non-operative treatment should be discussed in
      terms of the meaning and extent of the post-operative rehabilitation and the
      expected outcomes. There also seems to be a need for more guidance in realistic
      goal setting and coaching throughout the rehabilitation process.

PMID- 18067527
TI  - Factors affecting outcome after anterior cruciate ligament injury: a prospective
      study with a six-year follow-up.
AB  - The aim of this study was to investigate whether gender, age, stable personality
      traits, associated meniscus and/or articular cartilage injuries, treatment (non
      operative or reconstructive surgery), additional subsequent trauma to the
      anterior cruciate ligament (ACL)-injured knee and activity level before injury
      affect the intermediate outcome after ACL injury. The primary outcome was the
      Knee injury and Osteoarthritis Outcome Score (KOOS). Fifty-seven patients, 18-50
      years old with an acute, unilateral ACL tear were included in the study. At the
      time of inclusion, the patients completed the Tegner score, regarding activity
      level before injury, and Swedish universities Scales of Personality (SSP). At
      follow-up, after 5.6 years they completed the KOOS, the Tegner score and a
      general questionnaire concerning ACL reconstruction and subsequent knee trauma.
      The subjects who had sustained additional trauma subsequent to their ACL injury
      had a significantly worse outcome according to the KOOS than those who had not.
      Furthermore, low ratings in the embitterment scale in the SSP were correlated to
      a better outcome in the KOOS. Treatment did not affect the KOOS total score.
      However, the non-operatively treated subjects had a significantly better outcome
      according to the knee-related quality-of-life domain in the KOOS.

PMID- 18067528
TI  - Load-specific differences in the structure of femoral neck and tibia between
      world-class moguls skiers and slalom skiers.
AB  - Bone structure of weight-bearing proximal femur and tibia was examined among the
      Finnish world-class moguls skiers and slalom skiers. We hypothesized that these
      bones, during typical sport-specific performance, had been subjected not only to
      extreme loading but also to distinct loading in terms of rate and primary
      direction. Bone [dual-energy X-ray absorptiometry (DXA), peripheral quantitative
      computed tomography (pQCT), magnetic resonance imaging] and muscle performance
      data of the lower extremities were obtained from the five Finnish male moguls
      skiers and six slalom skiers competing at the World Cup level. Data (DXA, pQCT)
      from 12 age- and weight-matched normally active men were used for comparison. The
      ANCOVA with body height as a covariate was used for statistical analysis. The
      weight-bearing bones of the athletes were 10-60% stronger than those of the
      normally active men. Compared with the moguls skiers, the slalom skiers showed an
      average 43% thicker anterior cortex at the narrowest region of the femoral neck.
      This study suggests that the bone structure at skiers' heavily loaded lower
      extremities was very robust. A specific finding was the thick anterior cortex of
      the femoral neck among the slalom skiers. Apparently, the predominant loading
      type had modulated the site-specific skeletal response to physical exertion.

PMID- 18067529
TI  - Arabidopsis eIF3e is regulated by the COP9 signalosome and has an impact on
      development and protein translation.
AB  - The roles of individual eukaryotic translation initiation factor 3 (eIF3)
      subunits are largely unclear, although some are essential, while others are
      thought to have regulatory roles. The 'e' subunit, also known as Int-6/Int6, is a
      candidate for a regulatory subunit as it is not essential for translation
      initiation in yeasts. eIF3e associates with the COP9 signalosome, and localizes
      to the nucleus in certain tissues. To further elucidate the roles of eIF3e, we
      have taken a genetic approach using Arabidopsis as a model system. Overexpression
      of eIF3e results in defects similar to mutations in the COP9 signalosome. eIF3e
      protein, but not transcript, over accumulates in csn mutants, and eIF3e is
      degraded in a proteasome-dependent fashion. In vitro and in vivo assays suggest
      that excess eIF3e inhibits translation. We conclude that the COP9 signalosome
      maintains a precise regulation of eIF3e levels, which is necessary for normal
      development in Arabidopsis.

PMID- 18067530
TI  - Mechanical role of the leaf sheath in rattans.
AB  - Leaf sheaths of rattans are long, tubular and persistent and unlike many self
      supporting palms, extend far from the apex of the plant. The mechanical role of
      the leaf sheath was investigated in eight rattan species of the subfamily
      Calamoideae. The main objective was to analyse its influence on the mechanical
      architecture and contribution to the climbing habit. Bending mechanical
      properties were measured along climbing axes before and after removal of leaf
      sheaths. Results were related to stem and leaf sheath geometry and mechanical
      properties. Contribution of the leaf sheath to axial flexural rigidity was high
      (c. 90%) in the early stages of growth and towards the apex of older climbing
      axes for all climbing palms tested. Senescence and loss of the leaf sheath
      strongly influenced axial stiffness. A nonclimbing species, Calamus erectus,
      showed a different mechanical architecture. Although lacking secondary growth,
      palms have been able to develop successful climbers with a mechanical
      architecture broadly analogous to, although developmentally different from,
      dicotyledonous lianas. The role of the leaf sheath in modulating mechanical
      properties during ontogeny ought not to be neglected in studies on
      monocotyledons, as it possibly contributed significantly to the ways in which
      different growth forms have evolved in the group.

PMID- 18067531
TI  - Xylem hydraulic and photosynthetic function of Gnetum (Gnetales) species from
      Papua New Guinea.
AB  - Gnetum (Gnetales) species are suggested to be unique extant gymnosperms that have
      acquired high photosynthetic and transpiration capacities as well as greater
      xylem hydraulic capacity and efficiency compared with all other extant
      gymnosperms. This is because Gnetum is the only extant gymnosperm lineage that
      combines vessels, broad pinnate-veined leaves and an ecological distribution in
      wet, productive lowland tropical rainforest habitats. Yet, field-based
      observations on the group's ecophysiological performance are lacking. To test a
      hypothesis that Gnetum species are ecophysiologically analogous to light
      demanding woody tropical angiosperms, stem xylem hydraulic performance,
      photosynthesis and stomatal conductance were investigated in Gnetum as compared
      with a diverse group of co-occurring woody plants in a lowland tropical
      rainforest. It was found that Gnetum species combined low photosynthetic capacity
      and low stomatal conductances with a low stem water transport ability. The
      physiological observations are consistent with the general occurrence of Gnetum
      species in shady, primary forest habitats. These results on Gnetum ecophysiology
      indicate that the coupling of vessels, broad pinnate-veined leaves and the liana
      habit do not signal the evolution of a highly opportunistic, light-demanding life
      history in gymnosperms.

PMID- 18067532
TI  - Effect of exogenous GnRH at the time of artificial insemination on reproductive
      performance of Awassi ewes synchronized with progestagen-PMSG-PGF2alpha
      combination.
AB  - This study was carried out to investigate the efficacy of PGF(2alpha) for oestrus
      synchronization (ES) in Awassi ewes to which were administered the progestagen
      PMSG combination, and to evaluate the effect of the exogenous GnRH administration
      immediately after the artificial insemination (AI) on their pregnancy rate and
      lambing performance during the breeding season. The ewes (n = 33) were treated
      with an intravaginal sponge impregnated with 30 mg fluorogestane acetate for 12
      days and were injected with 500 IU PMSG at the time of removal of the sponge. The
      ewes were then divided into three equal groups of 11 ewes each. One millilitre of
      physiological saline (0.9% NaCl; placebo) was administered to each ewe in Group 1
      at the time of second AI. Approximately 4 microg GnRH (busereline) was injected
      to each ewe in Group 2 immediately after second AI. A total of 150 microg
      PGF(2alpha) (cloprostenole) was injected at the time of sponge removal on day 12
      and 4 microg GnRH immediately after the second AI was also treated to each ewe in
      Group 3. Intracervical AI with diluted fresh semen was performed twice at 12 and
      24 h following the onset of oestrus. The injection-oestrus onset and injection
      oestrus-end interval in Group 3 was significantly (p < 0.001) shorter than both
      Groups 1 and 2. Although the pregnancy rates of Groups 2 and 3 (81.8%; 9/11) were
      numerically higher than of Group 1 (63.6%; 7/11), the difference among the groups
      was statistically insignificant. The multiple birth rate of Group 3 was found
      higher than Groups 1 and 2. However, the number of single lambs of Group 1 was
      also higher than Groups 2 and 3 (p < 0.05). Despite the litter sizes of Groups 2
      (1.27; 14/11) and 3 (1.55; 17/11) being numerically higher than Group 1 (0.73;
      8/11), the differences among all the groups were statistically insignificant. In
      conclusion, the administration of PGF(2alpha) at the time of removal of the
      sponge shortens the injection oestrus-onset and oestrus-end interval in Awassi
      ewes treated with progestagen-PMSG. Additionally, exogenous GnRH treatment
      immediately after the AI increases the multiple birth rate of Awassi ewes
      synchronized with progestagen-PMSG-PGF(2alpha) combination.

PMID- 18067533
TI  - Diagnostic evaluation of fat to protein ratio in prolonged calving to conception
      interval using receiver operating characteristic analyses.
AB  - Evaluation of fat to protein ratio (FPR) in milk was performed for the prediction
      of calving to conception interval (CC) in dairy cows. Reproduction parameters of
      51 high yielding dairy cows were calculated from farm recording data and milk
      data record from a regular dairy control. Spearman rank correlation analysis was
      used to determine the correlation between reproductive parameters of the herd and
      the milk data record. In the time interval of 75-90 days postpartum the highest
      correlation was found between FPR and CC (r = 0.414, p < 0.05). Receiver
      operating characteristics (ROC) analysis was used to evaluate the FPR to
      distinguish between cows with different CC. The optimal cut-off value at FPR of
      1.34 provided the best discrimination power according to CC of 120 days. FPR at
      1.44 enabled us 91.7% correct identification of cows with CC above 140 days,
      where the highest area under the ROC curve of 0.759 and likelihood ratio of 7.2
      were observed. FPR </=1.19 was 2.86 times as likely to be found in cows with CC
      below as in cows with CC above 90 days. The FPR has been shown to be of benefit
      in the prediction of reproductive efficiency in dairy herds.

PMID- 18067534
TI  - Heterologous in vitro fertility evaluation of cryopreserved Iberian red deer
      epididymal spermatozoa with zona-intact sheep oocytes and its relationship with
      the characteristics of thawed spermatozoa.
AB  - A heterologous in vitro system, using zona-intact sheep oocytes, was used to
      evaluate the relationship between sperm factors of Iberian red deer thawed
      epididymal sperm and the percentage of cleaved oocytes. Epididymal spermatozoa
      were recovered from six males, diluted with freezing extender and cryopreserved.
      After thawing sperm motility (SM) and acrosome and membrane integrities were
      evaluated. Again, these parameters were assessed after incubation in freezing
      extender at 37 degrees C for 2 h. After cryopreservation the values for SM and
      acrosome and membrane integrities were high (approximately 80, 80 and 70%
      respectively). However, these values significantly decreased after incubation
      (approximately 59, 62 and 47% respectively). Red deer thawed epididymal sperm
      fertilized zona-intact sheep oocytes, although the percentage of cleaved oocytes
      was low (approximately 22%). No relationship was found between sperm parameters
      assessed after thawing and the percentage of cleaved oocytes. Likewise, any sperm
      parameter evaluated after incubation was assessed in relation to the percentage
      of cleaved oocytes. However, acrosome and membrane integrities were near to
      significance (p = 0.06 and p = 0.09 respectively). Then, we conducted a reduced
      model with these two variables and both were related to the percentage of cleaved
      oocytes (p = 0.02 and p = 0.04 respectively). Thus, acrosome and membrane
      integrities were related to the percentage of cleaved oocytes negatively and
      positively respectively. It was concluded that the classical parameters assessed
      in deer thawed sperm samples can be good predictors of the ability to fertilize
      zona-intact sheep oocytes.

PMID- 18067535
TI  - Bacterial isolates associated with dystocia and retained placenta in iraqi
      buffaloes.
AB  - The present study was conducted on 50 recently calved Iraqi Buffalo cows.
      Depending on the kind of parturition, buffalo cows were divided into two main
      groups, the first group had normal unassisted parturition (NP) (26 animals) and
      the second group with certain periparturent complications (PPC) (24 animals).
      After 24 h of parturition, these two groups were further subdivided into two
      groups as cows expel their foetal membranes in <24 h postpartum and referred as
      non-retained placenta (NRP) while cows that did not expel their foetal membrane
      after 24 h referred as retained placenta (RP). Sampling for bacteriology, uterine
      discharge for polymorphonuclear cells per cent and blood samples for
      polymorphonuclear neutrophil (PMN) and the enzyme creatine kinase activity were
      performed at 6, 24 and 48 h postpartum. In PPC group, the most prevalent bacteria
      after 6 h of calving were Escherichia coli, beta-haemolytic Streptococci and
      Lactobacillus acidophilus. Total bacterial isolates in the uterus of buffaloes
      with RP in PPC group after 24 and 48 h were 129 and 183 respectively. Among the
      isolates, Archanobacterium pyogenes, Fusobacterium necrophorum, Prevotella
      melaninogenicus and Staphylococcus aureus were the most prevalent isolates after
      48 h of RP buffaloes in PPC group. Polymorphonuclear neutrophil were
      significantly (p < 0.01) increased in the uterine discharge than in blood in
      buffaloes with RP in both PPC and NP groups. In conclusion, uterine contamination
      occurs as a result of postpartum ascending contamination by non-specific
      environmental organisms. The presence of Lactobacillus sp. in the uterus
      indicated a healthy uterus. Peripartum complications followed by retention of
      foetal membranes with the dominance of E. coli in the uterine lumen might favour
      the colonization of other bacteria including facultative anaerobic and strictly
      anaerobic in the uterine wall of buffaloes.

PMID- 18067536
TI  - Enhancement of ovulatory follicle development in maiden sheep by short-term
      supplementation with steam-flaked corn.
AB  - The effect of a short-term nutritional supplementation with steam-flaked corn on
      metabolism and folliculogenesis was evaluated in 14 maiden sheep. Oestrus was
      synchronized with two prostaglandin F(2alpha) doses given 10 days apart. From day
      11 to 15 of the oestrous cycle induced with prostaglandins, half of the ewes
      (group 2M) were supplemented with steam-flaked corn, double the daily maintenance
      ration of the control sheep (group 1M). Body weight and condition remained
      unaffected, but the energetic supply increased plasma concentrations of glucose
      (3.6 +/- 0.1 vs 4.3 +/- 0.1 mmol/l, p < 0.0001) for the first 4 days and 3
      hydroxybutyrate (0.323 +/- 0.58 vs 0.582 +/- 0.04 mmol/l, p < 0.005) from day 2
      to 4. The profile of insulin secretion was also affected by the treatment,
      increasing in group 2M to reach significant differences on days 13 and 14 (p <
      0.05). From similar values at the start of the food supply, the treatment induced
      a higher follicular development in group 2M (1.1 +/- 1.2 vs 7.4 +/- 1.06 total
      follicles in day 15, p < 0.05), as evidenced by the lineal increase in the number
      of larger follicles (>4 mm, p < 0.005). Then, the number of follicles >4 mm in
      size in 2M was around 60% higher on day 16 (7.86 +/- 0.45 vs 4.86 +/- 0.63, p <
      0.005). Thereafter, the mean number of corpora lutea per ewe was around 30%
      higher in group 2M (1.43 +/- 0.2 vs 1.10 +/- 0.1, although differences were not
      found to be statistically significant). These data suggest that the use of diets
      containing high starch sources, like the steam-flaked corn, increases
      folliculogenesis and ovulation rate in sheep and can be applied in short-term
      feeding practices.

PMID- 18067537
TI  - Frontotemporal dementia and Parkinsonism linked to chromosome 17 in a young
      Australian patient with the G389R Tau mutation.

PMID- 18067538
TI  - Inadequate inhibition of host RNA polymerase restricts T7 bacteriophage growth on
      hosts overexpressing udk.
AB  - Overexpression of udk, an Escherichia coli gene encoding a uridine/cytidine
      kinase, interferes with T7 bacteriophage growth. We show here that inhibition of
      T7 phage growth by udk overexpression can be overcome by inhibition of host RNA
      polymerase. Overexpression of gene 2, whose product inhibits host RNA polymerase,
      restores T7 phage growth on hosts overexpressing udk. In addition, rifampicin, an
      inhibitor of host RNA polymerase, restores the burst size of T7 phage on udk
      overexpressing hosts to normal. In agreement with these findings, suppressor
      mutants that overcome the inhibition arising from udk overexpression gain the
      ability to grow on hosts that are resistant to inhibition of RNA polymerase by
      gene 2 protein, and suppressor mutants that overcome a lack of gene 2 protein
      gain the ability to grow on hosts that overexpress udk. Mutations that eliminate
      or weaken strong promoters for host RNA polymerase in T7 DNA, and mutations in T7
      gene 3.5 that affect its interaction with T7 RNA polymerase, also reduce the
      interference with T7 growth by host RNA polymerase. We propose a general model
      for the requirement of host RNA polymerase inhibition.

PMID- 18067539
TI  - Different regions of Mlc and NagC, homologous transcriptional repressors
      controlling expression of the glucose and N-acetylglucosamine phosphotransferase
      systems in Escherichia coli, are required for inducer signal recognition.
AB  - Mlc and NagC are two homologous transcription factors which bind to similar DNA
      targets but for which the inducing signals and mechanisms of activation are very
      different. Displacing Mlc from its DNA binding sites necessitates its
      sequestration to the inner membrane via an interaction with PtsG (EIICB(Glc)),
      while NagC is displaced from its DNA targets by interacting with GlcNAc6P. We
      have isolated mutations in both proteins which prevent the inactivation of the
      repressors by growth on glucose or GlcNAc. These mutations are located in
      different and specific regions of each protein. For Mlc changes at the C-terminal
      make it a constitutive repressor and also prevent it from binding to EIIB(Glc).
      Mutations in NagC, at positions which form a structural motif resembling a
      glucose binding site in Mlc, produce permanently repressing forms of NagC,
      suggesting that this motif forms a GlcNAc6P binding site in NagC. The pattern of
      repression by chimeric proteins of NagC and Mlc confirms the importance of the C
      terminal region of Mlc for both repression and inducer binding and demonstrate
      that the helix-turn-helix DNA-binding motif is not sufficient to determine the
      specificity of interaction of the repressor with DNA.

PMID- 18067540
TI  - Characterization of the metalloactivation domain of an arsenite/antimonite
      resistance pump.
AB  - The ArsAB extrusion pump encoded by the ars operon of Escherichia coli plasmid
      R773 confers resistance to the toxic trivalent metalloids arsenite [As(III)] and
      antimonite [Sb(III)]. The ArsA ATPase, the catalytic subunit of the pump, has two
      homologous halves, A1 and A2. At the interface of these two halves are two
      nucleotide-binding domains and a metalloid-binding domain. Cys-113 and Cys-422
      have been shown to form a high-affinity metalloid binding site. The crystal
      structure of ArsA shows two other bound metalloid atoms, one liganded to Cys-172
      and His-453, and the other liganded to His-148 and Ser-420. The contribution of
      those putative metalloid sites was examined. There was little effect of
      mutagenesis of residues His-148 and Ser-420 on metalloid binding. However, a
      C172A ArsA mutant and C172A/H453A double mutant exhibited significantly decreased
      affinity for Sb(III). These results suggest first that there is only a single
      high-affinity metalloid binding site in ArsA, and second that Cys-172 controls
      the affinity of this site for metalloid and hence the efficiency of
      metalloactivation of the ArsAB efflux pump.

PMID- 18067541
TI  - Multiple Ku orthologues mediate DNA non-homologous end-joining in the free-living
      form and during chronic infection of Sinorhizobium meliloti.
AB  - The bacterial non-homologous end-joining (NHEJ) apparatus is a two-component
      system that uses Ku and LigD to repair DNA double-strand breaks. Although the
      reaction mechanism has been extensively studied, much less is known about the
      physiological role of bacterial NHEJ. Recent studies suggest that NHEJ acts under
      conditions where DNA replication is reduced or absent (such as in a spore or
      stationary phase). Interestingly, genes encoding Ku and LigD have been identified
      in a wide range of bacteria that can chronically infect eukaryotic hosts.
      Strikingly, Sinohizobium meliloti, an intracellular symbiont of legume plants,
      carries four genes encoding Ku homologues (sku1 to sku4). Deletion analysis of
      the sku genes indicated that all Ku homologues are functional. One of these
      genes, sku2, is strongly expressed in free-living cells, as well as in bacteroid
      cells residing inside of the host plant. To visualize the NHEJ apparatus in vivo,
      SKu2 protein was fused to yellow fluorescent protein (YFP). Ionizing radiation
      (IR) induced focus formation of SKu2-YFP in free-living cells in a dosage
      dependent manner. Moreover, SKu2-YFP foci formed in response to IR in non
      dividing bacteroids, indicating that NHEJ system is functional even during the
      chronic infection phase of symbiosis.

PMID- 18067542
TI  - Genomic rearrangements and transcriptional analysis of the spliced leader
      associated retrotransposon in RNA interference-deficient Trypanosoma brucei.
AB  - The Trypanosoma brucei genome is colonized by the site-specific non-LTR
      retrotransposon SLACS, or spliced leader-associated conserved sequence, which
      integrates exclusively into the spliced leader (SL) RNA genes. Although there is
      evidence that the RNA interference (RNAi) machinery regulates SLACS transcript
      levels, we do not know whether RNAi deficiency affects the genomic stability of
      SLACS, nor do we understand the mechanism of SLACS transcription. Here, we report
      that prolonged culturing of RNAi-deficient T. brucei cells, but not wild-type
      cells, results in genomic rearrangements of SLACS. Furthermore, two populations
      of SLACS transcripts persist in RNAi-deficient cells: a full-length transcript of
      approximately 7 kb and a heterogeneous population of small SLACS transcripts
      ranging in size from 450 to 550 nt. We provide evidence that SLACS transcription
      initiates at the +1 of the interrupted SL RNA gene and proceeds into the 5' UTR
      and open reading frame 1 (ORF1). This transcription is carried out by an RNA
      polymerase with alpha-amanitin sensitivity reminiscent of SL RNA synthesis and is
      dependent on the SL RNA promoter. Additionally, we show that both sense and
      antisense small SLACS transcripts originate from ORF1 and that they are
      associated with proteins in vivo. We speculate that the small SLACS transcripts
      serve as substrates for the production of siRNAs to regulate SLACS expression.

PMID- 18067543
TI  - Electron tomography of the Maurer's cleft organelles of Plasmodium falciparum
      infected erythrocytes reveals novel structural features.
AB  - During intraerythrocytic development, the human malaria parasite, Plasmodium
      falciparum, establishes membrane-bound compartments, known as Maurer's clefts,
      outside the confines of its own plasma membrane. The Maurer's compartments are
      thought to be a crucial component of the machinery for protein sorting and
      trafficking; however, their ultrastructure is only partly defined. We have used
      electron tomography to image Maurer's clefts of 3D7 strain parasites. The
      compartments are revealed as flattened structures with a translucent lumen and a
      more electron-dense coat. They display a complex and convoluted morphology, and
      some regions are modified with surface nodules, each with a circular cross
      section of approximately 25 nm. Individual 25 nm vesicle-like structures are also
      seen in the erythrocyte cytoplasm and associated with the red blood cell
      membrane. The Maurer's clefts are connected to the red blood cell membrane by
      regions with extended stalk-like profiles. Immunogold labelling with specific
      antibodies confirms differential labelling of the Maurer's clefts and the
      parasitophorous vacuole and erythrocyte membranes. Spot fluorescence
      photobleaching was used to demonstrate the absence of a lipid continuum between
      the Maurer's clefts and parasite membranes and the host plasma membrane.

PMID- 18067544
TI  - Identification and functional analysis of novel (p)ppGpp synthetase genes in
      Bacillus subtilis.
AB  - Bacterial alarmone (p)ppGpp, is a global regulator responsible for the stringent
      control. Two homologous (p)ppGpp synthetases, RelA and SpoT, have been identified
      and characterized in Escherichia coli, whereas Gram-positive bacteria such as
      Bacillus subtilis have been thought to possess only a single RelA-SpoT enzyme. We
      have now identified two genes, yjbM and ywaC, in B. subtilis that encode a novel
      type of alarmone synthetase. The predicted products of these genes are relatively
      small proteins ( approximately 25 kDa) that correspond to the (p)ppGpp synthetase
      domain of RelA-SpoT family members. A database survey revealed that genes
      homologous to yjbM and ywaC are conserved in certain bacteria belonging to
      Firmicutes or Actinobacteria phyla but not in other phyla such as Proteobacteria.
      We designated the proteins as small alarmone synthetases (SASs) to distinguish
      them from RelA-SpoT proteins. The (p)ppGpp synthetase function of YjbM and YwaC
      was confirmed by genetic complementation analysis and by in vitro assay of enzyme
      activity. Molecular genetic analysis also revealed that ywaC is induced by
      alkaline shock, resulting in the transient accumulation of ppGpp. The SAS
      proteins thus likely function in the biosynthesis of alarmone with a mode of
      action distinct from that of RelA-SpoT homologues.

PMID- 18067545
TI  - The coronary arteries of the C57BL/6 mouse strains: implications for comparison
      with mutant models.
AB  - There are few detailed descriptions of the coronary arterial patterns in the
      mouse. Some recent reports on coronary anomalies in mutant mouse models have
      uncovered the importance of several genes (i.e. iv and connexin43) in coronary
      morphogenesis. These mutations spontaneously appeared (iv) or were generated
      (connexin43) in a C57BL/6 background, which is widely used for the development of
      mutant mice. We have studied the origin and course of the main coronary arteries
      of two C57BL/6 mouse strains. Unusual anatomical coronary arterial patterns were
      found, including: solitary ostium in aorta, accessory ostium, high take-off,
      aortic intramural course, slit-like ostium, sinus-like ostium and origin of a
      septal artery from the left coronary artery. In humans, some of these conditions
      are clinically relevant. Most of these patterns, which differ from those observed
      in wild mice and Swiss albino mice, coincide with those previously found in iv/iv
      and connexin43 knockout mice. The results indicate that there is variability in
      the coronary arterial arrangement of the laboratory mouse. Care should be taken
      when analysing coronary phenotypes of mutant mouse models.

PMID- 18067546
TI  - Maternal diabetes affects specific extracellular matrix components during
      placentation.
AB  - During embryo implantation, invasive trophoblast cells mediate embryo invasion
      into the decidualized stroma, forming a rich network of lacunae that connect the
      embryonic tissues to the maternal blood vessels. Placentation is probably guided
      by the composition and organization of the endometrial extracellular matrix.
      Certain pathological conditions that occur during pregnancy, including diabetes,
      have been linked to abnormal placental morphology and consequent fetal morbidity.
      We used immunoperoxidase techniques to identify members of the collagen,
      proteoglycan and glycoprotein families in the various compartments of the rat
      placenta and to determine whether experimentally induced diabetes affects
      placental morphology and alters the distribution of these molecules during
      pregnancy. Single injections of alloxan (40 mg kg(-1) i.v.) were used to induce
      diabetes on day 2 of pregnancy in Wistar rats. Placentas were collected on days
      14, 17, and 20. Type I and III collagen, as well as the proteoglycans decorin and
      biglycan, were found to be distributed throughout the placentas of control and
      diabetic rats. In both groups, laminin expression decreased at the end of
      pregnancy. In contrast, fibronectin was detected in the labyrinth region of
      diabetic rats at all gestational stages studied, whereas it was detected only at
      term pregnancy in the placentas of control rats. These results show for the first
      time that some extracellular matrix molecules are modulated during placental
      development. However, as diabetic rats presented increased fibronectin deposition
      exclusively in the labyrinth region, we speculate that diabetes alters the
      microenvironment at the maternal-fetal interface, leading to developmental
      abnormalities in the offspring.

PMID- 18067548
TI  - Molecular changes in the intermediate medial mesopallium after a one trial
      avoidance learning in immature and mature chickens.
AB  - Because brain maturation in chickens is protracted and occurs well after the
      major developmental period of synaptogenesis, chicken forebrain is suitable to
      investigate whether the molecular mechanisms underlying memory consolidation are
      different in immature and mature animals. We have used antibodies and western
      blotting to analyze subcellular fractions from the intermediate medial
      mesopallium region of 14-day and 8-week chicken forebrain prepared 0, 45, and 120
      min after learning a discriminative taste avoidance task. At both ages learning
      induced changes in the phosphorylation of the glutamate receptor subunit 1 at
      Ser831, the levels of calcium-calmodulin stimulated/dependent protein kinase II
      and the phosphorylation of calcium-calmodulin stimulated/dependent protein kinase
      II at Thr286 were observed only in the fraction enriched in post-synaptic
      densities. The changes were of the same type at the two ages but occurred faster
      in mature animals. The changes in extracellular signal regulated kinase and
      phosphorylated-extracellular signal regulated kinase were more complex with
      different subcellular fractions showing different patterns of change at the two
      ages. These results imply that the molecular changes induced by learning a
      behavioral task are faster in mature than immature brain and may involve a
      different balance of intracellular signaling pathways.

PMID- 18067547
TI  - Oxidative stress and protein oxidation in the brain of water drinking and alcohol
      drinking rats administered the HIV envelope protein, gp120.
AB  - Possible roles of oxidative stress and protein oxidation on alcohol-induced
      augmentation of cerebral neuropathy in gp120 administered alcohol preferring rats
      drinking either pure water (W rats) or a free-choice ethanol and water (E rats)
      for 90 days. This study showed that peripherally administered gp120 accumulated
      into the brain, liver, and RBCs samples from water drinking - gp120 administered
      rats (Wg rats) and ethanol drinking - gp120 administered rats (Eg rats), although
      gp120 levels in samples from Eg rats were significantly greater than the levels
      in samples from Wg rats. The brain samples from ethanol drinking-saline
      administered (EC) and Wg rats exhibited comparable levels of free radicals that
      were significantly lower than the levels in Eg rats. Peroxiredoxin-I (PrxI)
      activity in the brain samples exhibited the following pattern: Wg >> >> WC >> EC
      > Eg. Total protein-carbonyl and carbonylated hippocampal cholinergic
      neurostimulating peptide precursor protein levels, but not N-acetylaspartate or N
      acetyl aspartylglutamate or total protein-thiol levels, paralleled the free
      radical levels in the brain of all four groups. This suggests PrxI inhibition may
      be more sensitive indicator of oxidative stress than measuring free radicals or
      metabolites. As PrxI oxidation in WC, Wg, and EC rats was reversible, while PrxI
      oxidation in Eg rats was not, we suggest that alcohol drinking and gp120 together
      hyperoxidized and inactivated PrxI that suppressed free radical neutralization in
      the brain of Eg rats. In conclusion, chronic alcohol drinking, by carbonylating
      and hyperoxidizing free radical neutralization proteins, augmented the gp120
      induced oxidative stress that may be associated with an increase in severity of
      the brain neuropathy.

PMID- 18067549
TI  - Activation of P2X(7) receptors decreases glutamate uptake and glutamine
      synthetase activity in RBA-2 astrocytes via distinct mechanisms.
AB  - Glutamate clearance by astrocytes is critical for controlling excitatory
      neurotransmission and ATP is an important mediator for neuron-astrocyte
      interaction. However, the effect of ATP on glutamate clearance has never been
      examined. Here we report that treatment of RBA-2 cells, a type-2-like astrocyte
      cell line, with ATP and the P2X(7) receptor selective agonist 3'-O-(4
      benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) decreased the Na+-dependent
      [3H]glutamate uptake within minutes. Mechanistic studies revealed that the
      decreases were augmented by removal of extracellular Mg2+ or Ca2+, and was
      restored by P2X7 selective antagonist , periodate-oxidized 2',3'-dialdehyde ATP
      (oATP), indicating that the decreases were mediated through P2X(7) receptors.
      Furthermore, stimulation of P2X7 receptors for 2 h inhibited both activity and
      protein expression of glutamine synthetase (GS), and oATP abolished the
      inhibition. In addition, removal of extracellular Ca(2+) and inhibition of
      protein kinase C (PKC) restored the ATP-decreased GS expression but failed to
      restore the P2X(7)-decreased [3H]glutamate uptake. Therefore, P2X7-mediated
      intracellular signals play a role in the down-regulation of GS
      activity/expression. Activation of P2X7 receptors stimulated increases in
      intracellular Na+ concentration ([Na+](i)) suggesting that the P2X(7)-induced
      increases in [Na+](i) may affect the local Na+ gradient and decrease the Na+
      dependent [3H]glutamate uptake. These findings demonstrate that the P2X7-mediated
      decreases in glutamate uptake and glutamine synthesis were mediated through
      distinct mechanisms in these cells.

PMID- 18067550
TI  - Tumor necrosis factor-alpha stimulates gingival epithelial cells to release high
      mobility-group box 1.
AB  - BACKGROUND AND OBJECTIVE: High-mobility-group box 1 functions as a late-phase
      inflammatory mediator. It can be released extracellularly by macrophages and
      necrotic cells through lipopolysaccharide and tumor necrosis factor-alpha. The
      objective of this study was to clarify the source of high-mobility-group box 1 in
      chronic periodontitis tissues and tumor necrosis factor-alpha-stimulated gingival
      epithelial cells, and subsequently elucidate its inducible inflammatory pathway.
      MATERIAL AND METHODS: Chronic periodontitis and healthy gingival sections were
      stained for high-mobility-group box 1 by immunohistochemistry and
      immunofluorescence. The amounts of high-mobility-group box 1 released into the
      gingival crevicular fluid and supernatants from gingival epithelial cells
      stimulated by tumor necrosis factor-alpha were examined by western blot. The
      phosphorylation of mitogen-activated protein kinases (MAPKs) in gingival
      epithelial cells was also examined. RESULTS: High-mobility-group box 1 was
      detected in the cytoplasm and nucleus of gingival epithelial cells with
      periodontitis. Western blotting revealed a significant increase in high-mobility
      group box 1 expression in the gingival crevicular fluid from periodontitis
      patients. High-mobility-group box 1 production in gingival epithelial cells was
      increased following stimulation with tumor necrosis factor-alpha. The molecular
      dialogue between tumor necrosis factor-alpha and gingival epithelial cells
      involved modulation of the activities of p38MAPK, Jun N-terminal kinase and
      p44/42. Interestingly, only phosphorylation of p38MAPK contributed to more than
      half of the signaling initiated by tumor necrosis factor-alpha-elicited high
      mobility-group box 1 release. CONCLUSION: High-mobility-group box 1 is
      continuously released from the gingival epithelial cells modulated by tumor
      necrosis factor-alpha. These findings imply that high-mobility-group box 1
      expression and possibly p38MAPK constitute important features in periodontitis.

PMID- 18067551
TI  - Association of F11 receptor gene polymorphisms with central obesity and blood
      pressure.
AB  - OBJECTIVES: F11 receptor, also known as junctional adhesion molecule-1, in the
      autonomic nervous system is implicated in the development of hypertension in
      spontaneous hypertensive rats. We investigated the association of single
      nucleotide polymorphisms (SNPs) in the F11 receptor gene (F11R) with hypertension
      and central obesity in Hong Kong Chinese. METHODS: Seven tagging SNPs were
      identified in the HapMap database. Genotyping was performed using Sequenom
      MassArray in 263 hypertensive subjects and 393 normotensive controls, of whom 263
      matched the cases in age and sex. RESULTS: When subjects on anti-hypertensive
      medication were excluded, rs790056 and rs2774276 were associated with lower
      systolic blood pressure (TT:124.8 +/- 18.3 mmHg vs. TC + CC: 120.2 +/- 15.5 mmHg,
      P = 0.004 and CC: 124.7 +/- 18.5 mmHg vs. CG+GG: 120.5 +/- 15.1 mmHg, P = 0.007
      respectively). Comparing 213 subjects with central obesity with 213 controls
      matched for sex and age, rs2481084 and rs3737787 were associated with lower odds
      of central obesity (odds ratio = 0.516, P = 0.002 and odds ratio = 0.540, P =
      0.005 respectively). All these associations remained significant after correction
      for multiple testing. Analysis of statistically similar SNPs suggested that the
      causative variants for systolic blood pressure were located in F11R, whilst those
      for central obesity could be due to causative variants in the transcription
      factor 1 gene immediately upstream. CONCLUSIONS: F11 receptor plays a role in
      blood pressure regulation, not only in rats but also in man. The link between F11
      receptor and central obesity merits further investigation.

PMID- 18067552
TI  - Effects of a stress management program on vital exhaustion and depression in
      women with coronary heart disease: a randomized controlled intervention study.
AB  - OBJECTIVES: Psychosocial factors, including depression and vital exhaustion (VE)
      are associated with adverse outcome in coronary heart disease (CHD). Women with
      CHD are poor responders to psychosocial treatment and knowledge regarding which
      treatment modality works in them is limited. This randomized controlled clinical
      study evaluated the effect of a 1-year stress management program, aimed at
      reducing symptoms of depression and VE in CHD women. DESIGN: Patients were 247
      women, < or =75 years, recruited consecutively after a cardiac event and randomly
      assigned to either stress management (20 2-h sessions) and medical care by a
      cardiologist, or to obtaining usual health care as controls. Measurements at;
      baseline (6-8 weeks after randomization), 10 weeks (after 10 intervention
      sessions), 1 year (end of intervention) and 1-2 years follow-up. RESULTS: For VE,
      intention to treat analysis showed effects for time (P < 0.001) and time x
      treatment interaction (P = 0.005), reflecting that both groups improved over
      time, and that the decrease of VE was more pronounced in the intervention group.
      However, the level of VE was higher in the intervention group than amongst
      controls at baseline, 22.7 vs. 19.4 (P = 0.036) but it did not differ later. The
      change in depressive symptoms did not differ between the groups. CONCLUSIONS: CHD
      women attending our program experienced a more pronounced decrease in VE than
      controls. However, as they had higher baseline levels, due to regression towards
      the mean we cannot attribute the decrease in VE to the intervention. Whether the
      program has long-term beneficial effects needs to be evaluated.

PMID- 18067553
TI  - Apoptotic cells induce dendritic cell-mediated suppression via interferon-gamma
      induced IDO.
AB  - Dendritic cells (DC) are sensitive to their local environment and are affected by
      proximal cell death. This study investigated the modulatory effect of cell death
      on DC function. Monocyte-derived DC exposed to apoptotic Jurkat or primary T
      cells failed to induce phenotypic maturation of the DC and were unable to support
      CD4+ allogeneic T-cell proliferation compared with DC exposed to
      lipopolysaccharide (LPS) or necrotic cells. Apoptotic cells coincubated with LPS-
      or necrotic cell-induced mature DC significantly suppressed CD80, CD86 and CD83
      and attenuated LPS-induced CD4+ T-cell proliferation. Reduced levels of
      interleukin-12 (IL-12), IL-10, IL-6, tumour necrosis factor-alpha and interferon
      gamma (IFN-gamma) were found to be concomitant with the suppressive activity of
      apoptotic cells upon DC. Furthermore, intracellular staining confirmed IFN-gamma
      expression by DC in association with apoptotic environments. The specific
      generation of IFN-gamma by DC within apoptotic environments is suggestive of an
      anti-inflammatory role by the induction of indoleamine 2,3-dioxygenase (IDO).
      Both neutralization of IFN-gamma and IDO blockade demonstrated a role for IFN
      gamma and IDO in the suppression of CD4+ T cells. Moreover, we demonstrate that
      IDO expression within the DC was found to be IFN-gamma-dependent. Blocking
      transforming growth factor-beta (TGF-beta) also produced a partial release in T
      cell proliferation. Our study strongly suggests that apoptosis-induced DC
      suppression is not an immunological null event and two prime mediators
      underpinning these functional effects are IFN-gamma-induced IDO and TGF-beta.

PMID- 18067554
TI  - CD22: an inhibitory enigma.
AB  - CD22 is an inhibitory coreceptor of the B-cell receptor (BCR), and plays a
      critical role in establishing signalling thresholds for B-cell activation. Like
      other coreceptors, the ability of CD22 to modulate B-cell signalling is
      critically dependent upon its proximity to the BCR, and this in turn is governed
      by the binding of its extracellular domain to alpha2,6-linked sialic acid
      ligands. Manipulation of CD22 ligand binding in various experimental settings has
      profound effects on B-cell signalling, but as yet there is no complete model for
      how ligand binding in vivo controls normal CD22 function. Several elegant studies
      have recently shed light on this issue, although the results appear to suggest
      two mutually exclusive models for the role of ligand binding; in either promoting
      or inhibiting, CD22 function. We shall therefore discuss these results in detail,
      and suggest possible approaches by which these conflicting experimental findings
      might be reconciled. We shall also consider a second important issue in CD22
      biology, which relates to the role that defects in this receptor might play in
      mediating autoimmune disease. We review the current evidence for this, and
      discuss the importance of genetic background in modifying CD22 function and
      predisposition to autoimmunity.

PMID- 18067555
TI  - CD40 Ligand-activated, antigen-specific B cells are comparable to mature
      dendritic cells in presenting protein antigens and major histocompatibility
      complex class I- and class II-binding peptides.
AB  - Dendritic cells (DC) are increasingly exploited for cell-based immunotherapy.
      However, limitations in ex vivo DC growth and DC functional heterogeneity have
      motivated development of complementary antigen-presenting cell sources. Here, the
      ability of CD40 ligand (CD40L)-activated B cells to fulfil that role was
      investigated. We demonstrate for the first time that non-specific or antigen
      specific murine B cells can be grown for extended periods of time by stimulation
      with CD40L. These cells rapidly up-regulate and maintain high levels of co
      stimulatory molecules. In a head-to-head comparison with DC, CD40L-expanded B
      cells were comparable to DC in the presentation of peptides to CD4+ and CD8+ T
      cells. While DC were superior to antigen non-specific CD40L-activated B cells
      with regard to whole protein (NP-BSA) processing and presentation, CD40L-expanded
      B cells from NP-BSA-immunized mice were comparable to DC when presenting BSA or
      NP-BSA to primed primary T cells or when presenting NP linked to an unrelated
      carrier, CGG, to naive T cells. Thus, the combination of CD40L activation, which
      supports B-cell growth and augments intracellular protein processing, and antigen
      uptake via the B-cell receptor, allows for efficient uptake, processing, and
      presentation of whole protein antigens in a fashion comparable to that observed
      with mature DC. Like DC, CD40L-activated B cells efficiently home to secondary
      lymphoid organs in vivo. This system represents a unique tool for studying
      primary antigen-specific B cells and the results suggest that the outgrowth of
      large numbers of highly activated B cells represents a viable and practical
      complement to DC for cell-based immunotherapy.

PMID- 18067556
TI  - Regulatory T cells and tumour immunity - observations in mice and men.
AB  - An enormous body of work supports a role for CD4+ CD25+ regulatory cells (Tregs)
      in shaping the immune response to tumours. Indeed, there is evidence that the
      cells impede effective tumour immunosurveillance, inhibit vaccine-induced
      antitumour immune responses and promote tumour progression. Studies exploring the
      impact of Tregs on tumour development are discussed in the context of
      manipulating this T-cell population for the purpose of cancer immunotherapy.

PMID- 18067557
TI  - Sclerosed hemangioma of the liver: Report of a case and review of the literature.
AB  - A sclerosed hemangioma of the liver is an extremely rare type of benign hepatic
      tumor. A 77-year-old female was referred to Tokushima University Hospital with
      fever, abnormal liver function tests and a large liver mass. The tumor, 10 x 5 cm
      in size and located in segment 5-6 of the liver, was depicted as a low density
      tumor with enhancement by computed tomography (CT). Magnetic resonance imaging
      (MRI) showed it to be a tumor with a low signal on T1-weighted and a high signal
      on T2-weighted images. The patient was negative for hepatitis B surface antigen
      and hepatitis C antibody. She underwent a right hepatectomy for possible
      malignant liver tumors, including intrahepatic cholangiocarcinoma or
      fibrolamellar hepatocellular carcinoma. The following histological examination of
      the surgical specimen revealed the tumor to be a hepatic sclerosed hemangioma
      with characteristic dense collagenous tissues. We report here on the case of this
      unusual tumor and review the relevant literature.

PMID- 18067558
TI  - Satisfaction with tolterodine: assessing symptom-specific patient-reported goal
      achievement in the treatment of overactive bladder in female patients (STARGATE
      study).
AB  - AIMS: Open-label study to evaluate the effect of tolterodine extended-release
      (ER) on symptom-specific patient-reported goal achievement (PGA) of overactive
      bladder (OAB) symptoms in females. METHODS: Eligible patients who had frequency
      >or= 8 and urgency >or= 2 episodes per 24 h with or without urgency incontinence
      were treated with 12-week tolterodine ER (4 mg once daily). Primary end-point was
      the rate of PGA by a visual analogue scale compared with initial expectation with
      treatment. At baseline, patients were asked to set their personal goals for each
      OAB symptom with treatment. Secondary efficacy variables were changes in symptom
      severity, voiding diary and patient perception of bladder condition (PPBC),
      global impression of improvement (GII), and willingness to continue treatment.
      RESULTS: A total of 56 patients were entered. The median rate of symptom-specific
      PGA and reductions in symptom severity were for frequency (60%, 45%), episodes of
      urgency 60%, 55%), urge incontinence (80%, 71%), nocturia (50%, 52%) and tenesmus
      (30%, 26%) after 12 weeks treatment. There was a significant improvement in all
      OAB symptoms in voiding diary. Thirty-five patients (62.5%) experienced an
      improvement of >or= 2 points in PPBC. Thirty (53.6%) and 22 (39.3%) of patients
      reported much and little improvement of their symptoms in GII. A total of 41
      (73.2%) patients wanted to continue taking the medication at the end of the
      study. CONCLUSIONS: Most OAB patients reported improvement of their OAB symptoms
      with 12-week tolterodine ER 4 mg treatment. There was a significant achievement
      of symptom-specific goal on the key OAB symptoms. But, PGA did not correlate with
      objective outcomes.

PMID- 18067559
TI  - Unravelling the mystery of 'cautious fluids'.

PMID- 18067560
TI  - Patient-controlled sedation vs. anaesthetic nurse-controlled sedation for
      cataract surgery in elderly patients.
AB  - BACKGROUND: Patient-controlled sedation (PCS) with propofol has been used
      successfully in various conditions, but controversies exist about its use in
      sedation of elderly patients for cataract surgery. This study evaluates the
      efficacy of anaesthetic nurse-controlled sedation (ACS) compared with PCS using
      the same device and the drug. METHODS: All of the 153 elderly patients (aged 51
      88 years) undergoing cataract surgery with a sub-Tenon's infiltration were
      assigned to receive ACS (n = 51) or PCS (n = 51) with propofol or no intra
      operative sedation (control, n = 51). Propofol was administered with a bolus dose
      of 10 mg and a lockout interval of 1 min. Cognitive function, sedation, pain,
      anxiety, side effects and satisfaction of patients were evaluated. RESULTS: The
      mean +/- SD doses of propofol administered were 34.9 +/- 8.8 mg and 30.1 +/- 30.4
      mg in the groups ACS and PCS, respectively. The anxiety score was lower in both
      ACS and PCS groups compared with control group but was not different between the
      two groups. Patient's satisfaction was highest in PCS group, ACS group was the
      next, compared with non-sedated group. Other parameters were not different among
      the three groups. CONCLUSIONS: Both ACS and PCS using propofol provided reduced
      anxiety compared with control, but patient's satisfaction was higher in the PCS
      group compared with ACS group.

PMID- 18067561
TI  - Time-dependent benefit of initial thrombosuction on myocardial reperfusion in
      primary percutaneous coronary intervention.
AB  - BACKGROUND: In ST-segment elevation acute myocardial infarction (STEMI),
      dislodgement of thrombus within the culprit artery during primary percutaneous
      coronary intervention (PCI) may cause distal embolisation and impaired myocardial
      reperfusion. Clinical results of thromboembolic protection strategies have been
      controversial. We conducted this study to investigate whether the benefit of
      thrombus removal is time dependent. METHODS: Seventy-four STEMI patients within
      12 h from onset were randomised to receive either primary PCI with initial
      thrombosuction (IT) or standard strategy. Results were analysed in subgroups
      according to the onset-to-lab time intervals (subgroup 1: 0-240 min, subgroup 2:
      241-480 min and subgroup 3: 481-720 min). RESULTS: The primary end-points were
      improvements in thrombolysis in myocardial infarction flow (DeltaTIMI) and
      myocardial blush grade (DeltaMBG) postprocedure. Better DeltaTIMI (2.2 +/- 1.1
      vs. 1.5 +/- 1.3, p = 0.014) and DeltaMBG (2.3 +/- 1.1 vs. 1.0 +/- 1.5, p < 0.001)
      were observed in IT patients, compared with standard PCI patients. In onset-to
      lab time subgroup analysis, the difference between IT and standard PCI is
      significant only in subgroup 2 (DeltaTIMI 2.6 +/- 1.0 vs. 1.3 +/- 1.2, p = 0.007;
      DeltaMBG 2.6 +/- 0.9 vs. 1.0 +/- 1.1, p = 0.010), but not in the other two
      subgroups. CONCLUSIONS: This prospective randomised study shows that primary PCI
      with IT may improve epicardial flow and myocardial reperfusion in patients with
      STEMI, and this benefit is the most significant in patients treated within 4-8 h
      after symptom onset.

PMID- 18067562
TI  - Physical therapy in the management of women with chronic pelvic pain.
AB  - OBJECTIVES: Chronic pelvic pain (CPP) is defined as lower abdominal pain lasting
      for at least 6 months, which occurs continuously or intermittently and is not
      associated exclusively with menstruation or intercourse. CPP is a highly
      prevalent debilitating disease with negative impact on the quality of life and
      productivity of women. The dilemma regarding the management of CPP continues to
      frustrate the health professionals, partly because its physiopathology is poorly
      understood. Consequently, the treatment of this condition is often unsatisfactory
      and limited to temporary symptom relief. In the present review, we discuss
      characteristics of the clinical history and physical examination associated with
      musculoskeletal involvement in women with CPP and possible treatments, especially
      in the area of physiotherapy. METHODS: We evaluated data available in PubMed
      (1984-2006) and surveyed the reference list. Three reviewers analysed the data
      independently, considering a study to be of high quality if it had at least three
      of the following characteristics: prospective design, valid measurement
      instruments, and adequate sample estimate and response rate. Other studies such
      as retrospective investigations, reviews and expert opinions were also
      considered, but with decreasing emphasis. RESULTS: There are evidences of
      musculoskeletal system disorders in most women with CPP. These musculoskeletal
      disorders can be the primary cause of CPP or postural changes and pelvic muscle
      contractures secondary to CPP. CONCLUSIONS: Synchronised intervention by
      physicians and physiotherapists is becoming increasingly more necessary both in
      terms of a more refined diagnosis of the clinical situation and of the
      institution of effective and lasting treatment.

PMID- 18067563
TI  - Urinary phthalate metabolites and semen quality: a review of a potential
      biomarker of susceptibility.
AB  - Phthalates are a class of chemicals with widespread general population exposure.
      Some phthalates are reproductive and developmental toxicants in laboratory
      animals. Advances in the field of phthalate research in humans are dependent on
      the development and implementation of biomarkers to assess exposure and outcome,
      as well as potential markers that may be indicative of increased susceptibility.
      Recently, we incorporated a novel biomarker of potential 'susceptibility' into
      our study on the relationship of phthalates with semen quality and sperm DNA
      damage among men recruited from an infertility clinic. We measured urinary
      concentrations of three di(2-ethylhexyl) phthalate (DEHP) metabolites, mono(2
      ethylhexyl) phthalate (MEHP) and two oxidative metabolites, mono-(2-ethyl-5
      hydroxylhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP).
      We calculated the percent of DEHP excreted as the hydrolytic monoester (i.e.,
      MEHP). We referred to this as %MEHP and considered it a phenotypic marker of the
      proportion of DEHP excreted in the urine as MEHP. In our sperm DNA study, we
      found novel results for the DEHP metabolites. Although MEHP was positively
      correlated with the oxidative metabolites, the association of sperm DNA damage
      with MEHP, as compared to MEHHP and MEOHP, were in opposite directions. We
      hypothesized that MEHP is the bioactive toxicant and further metabolism to
      MEHHP/MEOHP may lower internal burden of MEHP and thus be protective from sperm
      DNA damage. An alternative explanation may include that the relative percentage
      of DEHP excreted as MEHP was a surrogate for the function of phase I enzymes. Men
      with high %MEHP may have higher levels of sperm DNA damage because of poor
      metabolism (detoxification) of other genotoxic chemicals. Our hypothesis that
      %MEHP may represent a phenotypic marker of metabolism is novel but requires
      further exploration to confirm.

PMID- 18067564
TI  - XPC gene polymorphisms and risk of idiopathic azoospermia or oligozoospermia in a
      Chinese population.
AB  - A retrospective case-control study was carried out in the Han-Chinese population
      to determine the polymorphisms of xeroderma pigmentosum complementation group C
      (XPC) gene on the risk of idiopathic azoospermia or oligozoospermia. The
      Ala499Val (C>T) and Lys939Gln (A>C) polymorphism of XPC gene were genotyped by
      polymerase chain reaction-restriction fragment length polymorphism in three
      groups of infertile men (172 patients of azoospermia, 25 patients of severe
      oligozoospermia, 55 patients of oligozoospermia) and 228 fertile men. Increased
      risk of idiopathic azoospermia, but not oligozoospermia was associated with the
      XPC variant genotypes of Ala499Val (C>T) [adjusted odds ratio (OR) = 1.67, 95%
      confidence interval (CI) = 1.04-2.68 for CT heterozygote and adjusted OR = 2.03,
      95% CI = 1.10-3.75 for TT homozygote] compared with CC homozygous wide-type. The
      Lys939Gln (A>C) polymorphism was not related to spermatogenic failure. The
      combined risk alleles analysis and haplotype analysis showed that ORs increased
      as the number of the risk alleles increased and the 499T-939C haplotype had a
      significantly increased risk of idiopathic azoospermia (OR = 7.97; 95% CI = 3.51
      18.07) compared with other haplotypes. The results suggest that XPC Ala499Val
      (C>T) polymorphism is correlated with high risk of idiopathic azoospermia in the
      Han-Chinese population.

PMID- 18067565
TI  - Endocrine-disrupting properties in vivo of widely used azole fungicides.
AB  - The endocrine-disrupting potential of four commonly used azole fungicides,
      propiconazole, tebuconazole, epoxiconazole and ketoconazole, were tested in two
      short-term in vivo studies. Initially, the antiandrogenic effects of
      propiconazole and tebuconazole (50, 100 and 150 mg/kg body weight/day each) were
      examined in the Hershberger assay. In the second study, pregnant Wistar rats were
      dosed with propiconazole, tebuconazole, epoxiconazole or ketoconazole (50
      mg/kg/day each) from gestational day (GD) 7 to GD 21. Caesarian sections were
      performed on dams at GD 21. Tebuconazole and propiconazole demonstrated no
      antiandrogenic effects at doses between 50 and 150 mg/kg body weight/day in the
      Hershberger assay. In the in utero exposure toxicity study, ketoconazole, a
      pharmaceutical to treat human fungal infections, decreased anogenital distance
      and reduced testicular testosterone levels, demonstrating a demasculinizing
      effect on male fetuses. Tebuconazole, epoxiconazole and ketoconazole induced a
      high-frequency of post-implantation loss, and both ketoconazole and epoxiconazole
      caused a marked increase in late and very late resorptions. Overall the results
      show that many of the commonly used azole fungicides act as endocrine disruptors
      in vivo, although the profile of action in vivo varies. As ketoconazole is known
      to implicate numerous endocrine-disrupting effects in humans, the concern for the
      effects of the other tested azole fungicides in humans is growing.

PMID- 18067566
TI  - Risk factors for deterioration of erectile function: the Krimpen study.
AB  - This report from the Krimpen study explored the relationship between the
      determinants for worsening of erectile function in the open population. In
      Krimpen aan den IJssel (a municipality near Rotterdam), all men aged 50-75 years,
      without cancer of the prostate or the bladder and without a history of radical
      prostatectomy or neurogenic bladder disease, were invited to participate in June
      1995. The response rate was 50%. The follow-up was until June 2004. At baseline a
      visit to a health centre for the measurement of urinalysis, height, weight and
      blood pressure was part of the ongoing study. During baseline and at the first
      follow-up, second follow-up and third follow-up, a self-administered booklet
      consisting of a compilation of validated questionnaires including the
      International Continence Society male sex questionnaire was completed. At the
      urology outpatient clinic, a urological workup was measured. All participants
      were asked to keep a frequency-volume chart for 3 days. A multivariate Cox
      proportional hazard model was constructed to find the determinants of worsening
      of erectile function, correcting for age. Total follow-up time was 4948 person
      years consisting of 975 men. During follow-up, 441 events of worsening of
      erectile function occurred. Multivariate Cox-proportional hazard ratio analyses
      showed that body mass index (BMI), irritative lower urinary tract symptoms,
      diabetes mellitus, chronic obstructive pulmonary disease (COPD) and sexual
      inactivity were determinants with significant hazard ratios. In addition to age,
      determinants for a deterioration of erectile function based on multivariate
      longitudinal analyses are BMI, diabetes mellitus, COPD, sexual inactivity and
      irritative IPSS. The mechanism of various determinants is discussed.

PMID- 18067567
TI  - Evolution of the genomic rate of recombination in mammals.
AB  - Rates of recombination vary considerably between species. Despite the
      significance of this observation for evolutionary biology and genetics, the
      evolutionary mechanisms that contribute to these interspecific differences are
      unclear. On fine physical scales, recombination rates appear to evolve rapidly
      between closely related species, but the mode and tempo of recombination rate
      evolution on the broader scale is poorly understood. Here, we use phylogenetic
      comparative methods to begin to characterize the evolutionary processes
      underlying average genomic recombination rates in mammals. We document a strong
      phylogenetic effect in recombination rates, indicating that more closely related
      species tend to have more similar average rates of recombination. We demonstrate
      that this phylogenetic signal is not an artifact of errors in recombination rate
      estimation and show that it is robust to uncertainty in the mammalian phylogeny.
      Neutral evolutionary models present good fits to the data and we find no evidence
      for heterogeneity in the rate of evolution in recombination across the mammalian
      tree. These results suggest that observed interspecific variation in average
      genomic rates of recombination is largely attributable to the steady accumulation
      of neutral mutations over evolutionary time. Although single recombination
      hotspots may live and die on short evolutionary time scales, the strong
      phylogenetic signal in genomic recombination rates indicates that the pace of
      evolution on this scale may be considerably slower.

PMID- 18067568
TI  - Operational sex ratio and density do not affect directional selection on male
      sexual ornaments and behavior.
AB  - Demographic parameters including operational sex ratio (OSR) and population
      density may influence the opportunity for, and strength of sexual selection.
      Traditionally, male-biased OSRs and high population densities have been thought
      to increase the opportunity for sexual selection on male sexual traits due to
      increased male competition for mates. Recent experimental evidence, however,
      suggests that male-biased OSRs might reduce the opportunity for sexual selection
      due to increased sexual coercion experienced by females. How OSR, density, and
      any resultant changes in the opportunity for sexual selection actually affect
      selection on male sexual traits is unclear. In this study, we independently
      manipulated OSR and density in the guppy (Poecilia reticulata) without altering
      the number of males present. We recorded male and female behavior and used DNA
      microsatellite data to assign paternity to offspring and estimate male
      reproductive success. We then used linear selection analyses to examine the
      effects of OSR and density on directional sexual selection on male behavioral and
      morphological traits. We found that females were pursued more by males in male
      biased treatments, despite no change in individual male behavior. There were no
      differences in sexual behavior experienced by females or performed by males in
      relation to density. Neither OSR nor density significantly altered the
      opportunity for sexual selection. Also, Although there was significant
      multivariate linear selection operating on males, neither OSR nor density altered
      the pattern of sexual selection on male traits. Our results suggest that
      differences in either OSR or density (independent of the number of males present)
      are unlikely to alter directional evolutionary change in male sexual traits.

PMID- 18067569
TI  - Accepting evolution.
AB  - Poor public perceptions and understanding of evolution are not unique to the
      developed and more industrialized nations of the world. International resistance
      to the science of evolutionary biology appears to be driven by both proponents of
      intelligent design and perceived incompatibilities between evolution and a
      diversity of religious faiths. We assessed the success of a first-year evolution
      course at the University of Cape Town and discovered no statistically significant
      change in the views of students before the evolution course and thereafter, for
      questions that challenged religious ideologies about creation, biodiversity, and
      intelligent design. Given that students only appreciably changed their views when
      presented with "facts," we suggest that teaching approaches that focus on
      providing examples of experimental evolutionary studies, and a strong emphasis on
      the scientific method of inquiry, are likely to achieve greater success. This
      study also reiterates the importance of engaging with students' prior
      conceptions, and makes suggestions for improving an understanding and
      appreciation of evolutionary biology in countries such as South Africa with an
      inadequate secondary science education system, and a dire lack of public
      engagement with issues in science.

PMID- 18067570
TI  - The geographical mosaic of coevolution in a plant-pollinator mutualism.
AB  - Although coevolution is widely accepted as a concept, its importance as a driving
      factor in biological diversification is still being debated. Because coevolution
      operates mainly at the population level, reciprocal coadaptations should result
      in trait covariation among populations of strongly interacting species. A long
      tongued fly (Prosoeca ganglbaueri) and its primary floral food plant
      (Zaluzianskya microsiphon) were studied across both of their geographical ranges.
      The dimensions of the fly's proboscis and the flower's corolla tube length varied
      significantly among sites and were strongly correlated with each other. In
      addition, the match between tube length of flowers and tongue length of flies was
      found to affect plant fitness. The relationship between flower tube length and
      fly proboscis length remained significant in models that included various
      alternative environmental (altitude, longitude, latitude) and allometric (fly
      body size, flower diameter) predictor variables. We conclude that coevolution is
      a compelling explanation for the geographical covariation in flower depth and fly
      proboscis length.

PMID- 18067571
TI  - Do Wolbachia-associated incompatibilities promote polyandry?
AB  - The genetic incompatibility avoidance hypothesis as an explanation for the
      polyandrous mating strategies (mating with more than one male) of females of many
      species has received significant attention in recent years. It has received
      support from both empirical studies and a meta-analysis, which concludes that
      polyandrous females enjoy increased reproductive success through improved
      offspring viability relative to monandrous females. In this study we investigate
      whether polyandrous female Drosophila simulans improve their fitness relative to
      monandrous females in the face of severe Wolbachia-associated reproductive
      incompatibilities. We use the results of this study to develop models that test
      the predictions that Wolbachia should promote polyandry, and that polyandry
      itself may constrain the spread of Wolbachia. Uniquely, our models allow
      biologically relevant rates of incompatibility to coevolve with a polyandry
      modifier allele, which allows us to evaluate the fate of the modifier and that of
      Wolbachia. Our empirical results reveal that polyandrous females significantly
      reduce the reproductive costs of Wolbachia, owing to infected males being poor
      sperm competitors. The models show that this disadvantage in sperm competition
      can inhibit or prevent the invasion of Wolbachia. However, despite the increased
      reproductive success obtained by polyandrous females, the spread of a polyandry
      modifier allele is constrained by any costs that might be associated with
      polyandry and the low frequency of incompatible matings when Wolbachia has
      reached a stable equilibrium. Therefore, although incompatibility avoidance may
      be a benefit of polyandry, our findings do not support the hypothesis that
      genetic incompatibilities caused by Wolbachia promote the evolution of polyandry.

PMID- 18067572
TI  - Reproductive conflicts affect labor and immune defense in the queenless ant
      Diacamma sp. "nilgiri".
AB  - In many species of social Hymenoptera, totipotency of workers induces potential
      conflicts over reproduction. However, actual conflicts remain rare despite the
      existence of a high reproductive skew. One of the current hypotheses assumes that
      conflicts are costly and thus selected against. We studied the costs of conflicts
      in 20 colonies of the queenless ant Diacamma sp. "nilgiri" by testing the effects
      of conflicts on labor and worker immunocompetence, two parameters closely linked
      to the indirect fitness of workers. In this species, the dominant female is the
      only mated worker (gamergate) and monopolizes reproduction. We experimentally
      induced conflicts by splitting each colony into two groups, a control group
      containing the gamergate and an orphaned group displaying aggressions until a new
      dominant worker arises. Immunocompetence was assessed by the clearance of
      Escherichia coli bacteria that we injected into the ants. Time budget analysis
      revealed a lower rate of labor and especially brood care in orphaned groups,
      supporting the existence of a cost of conflicts on labor. Fifteen days after
      splitting, a lower immunocompetence was also found in orphaned groups, which
      concerned workers involved and not involved in conflicts. We propose that this
      immunosuppression induced by conflicts could stem from stress and not directly
      from aggression.

PMID- 18067573
TI  - Effects of reproductive compensation, gamete discounting and reproductive
      assurance on mating-system diversity in hermaphrodites.
AB  - Hermaphroditism allows considerable scope for contributing genes to subsequent
      generations through various mixtures of selfed and outcrossed offspring. The
      fitness consequences of different family compositions determine the
      evolutionarily stable mating strategy and depend on the interplay of genetic
      features, the nature of mating, and factors that govern offspring development.
      This theoretical article considers the relative contributions of these influences
      and their interacting effects on mating-system evolution, given a fixed genetic
      load within a population. Strong inbreeding depression after offspring gain
      independence selects for exclusive outcrossing, regardless of the intensity of
      predispersal inbreeding depression, unless insufficient mating limits offspring
      production. The extent to which selfing evolves under weak postdispersal
      inbreeding depression depends on predispersal inbreeding depression and the
      opportunity for resource limitation of offspring production. Mixed selfing and
      outcrossing is an evolutionarily stable strategy (ESS) if selfed zygotes survive
      poorly, but selfed offspring survive well, and maternal individuals produce
      enough "extra" eggs that deaths of unviable outcrossed embryos do not impact
      offspring production (reproductive compensation). Mixed mating can also be an
      ESS, despite weak lifetime inbreeding depression, if self-mating reduces the
      number of male gametes available for outcrossing (male-gamete discounting).
      Reproductive compensation and male-gamete discounting act largely independently
      on mating-system evolution. ESS mating systems always involve either complete
      fertilization or fertilization of enough eggs to induce resource competition
      among embryos, so although reproductive assurance is adaptive with insufficient
      mating, it is never an ESS. Our results illustrate the theoretical importance of
      different constraints on offspring production (availability of male gametes, egg
      production, and maternal resources) for both the course and outcome of mating
      system evolution, whereas unequal competition between selfed and outcrossed
      embryos has limited effect. These results also underscore the significance of
      heterogeneity in the nature and intensity of inbreeding depression during the
      life cycle for the evolution of hermaphrodite mating systems.

PMID- 18067575
TI  - The role of disulfide bond isomerase A (DsbA) of Escherichia coli O157:H7 in
      biofilm formation and virulence.
AB  - The role of periplasmic disulfide oxidoreductase DsbA in Shiga toxin-producing
      Escherichia coli O157:H7 (STEC) was investigated. Deletion of dsbA (DeltadsbA)
      significantly decreased cell motility and alkaline phosphatase activity in STEC.
      STEC DeltadsbA also showed greater sensitivity to menadione and under low pH
      conditions. Significant reductions in surface attachment to both biotic (HT-29
      epithelial cells) and abiotic (polystyrene and polyvinyl chloride) surfaces were
      observed in STEC DeltadsbA. In addition, no biofilm formation was detected in
      STEC DeltadsbA compared to wild-type cells in glass capillary tubes under
      continuous flow-culture system conditions. In the nematode model Caenorhabditis
      elegans-killing assay, the deletion of dsbA in STEC resulted in attenuated
      virulence compared to wild-type cells. STEC DeltadsbA was also found to have a
      reduced ability to colonize the nematode gut. These results suggest that DsbA
      plays important roles in biofilm formation and virulence in STEC cells.

PMID- 18067576
TI  - Identification of residues essential for the catalytic activity of Sec11b, one of
      the two type I signal peptidases of Haloferax volcanii.
AB  - Sec11b is one of two signal peptidases (SPases) in the haloarchaeon Haloferax
      volcanii. Site-directed mutagenesis revealed Ser-72, His-137 and Asp-187 as
      essential for signal peptide cleavage. Thus, like the SPase of the
      methanoarchaeon Methanococcus voltae, H. volcanii Sec11b uses a catalytic
      mechanism reminiscent of its eukaryal rather than its bacterial counterpart. The
      availability of an additional model system to study the archaeal SPase, now in
      the form of the purified protein, promises additional insight into the behavior
      of this enzyme.

PMID- 18067574
TI  - Genome-wide quantitative trait locus association scan of general cognitive
      ability using pooled DNA and 500K single nucleotide polymorphism microarrays.
AB  - General cognitive ability (g), which refers to what cognitive abilities have in
      common, is an important target for molecular genetic research because
      multivariate quantitative genetic analyses have shown that the same set of genes
      affects diverse cognitive abilities as well as learning disabilities. In this
      first autosomal genome-wide association scan of g, we used a two-stage
      quantitative trait locus (QTL) design with pooled DNA to screen more than 500,000
      single nucleotide polymorphisms (SNPs) on microarrays, selecting from a sample of
      7000 7-year-old children. In stage 1, we screened for allele frequency
      differences between groups pooled for low and high g. In stage 2, 47 SNPs
      nominated in stage 1 were tested by individually genotyping an independent sample
      of 3195 individuals, representative of the entire distribution of g scores in the
      full 7000 7-year-old children. Six SNPs yielded significant associations across
      the normal distribution of g, although only one SNP remained significant after a
      false discovery rate of 0.05 was imposed. However, none of these SNPs accounted
      for more than 0.4% of the variance of g, despite 95% power to detect associations
      of that size. It is likely that QTL effect sizes, even for highly heritable
      traits such as cognitive abilities and disabilities, are much smaller than
      previously assumed. Nonetheless, an aggregated 'SNP set' of the six SNPs
      correlated 0.11 (P < 0.00000003) with g. This shows that future SNP sets that
      will incorporate many more SNPs could be useful for predicting genetic risk and
      for investigating functional systems of effects from genes to brain to behavior.

PMID- 18067577
TI  - Psychrophilic yeasts in glacial environments of Alpine glaciers.
AB  - The presence of psychrophilic yeasts in supra- and subglacial sediments, ice and
      meltwater collected from two glaciers of the Italian Alps (Forni and Sforzellina
      Ortles-Cevedale group) was investigated. After incubation at 4 degrees C,
      subglacial sediments contained from 1.3 x 10(3) to 9.6 x 10(3) CFU of yeasts g(
      1). The number of yeast cells in supraglacial sediments was c. 10-100-fold lower.
      A significant proportion of isolated yeasts exhibited one or more extracellular
      enzymatic activities (starch-degrading, lipolytic, esterolytic, proteolytic and
      pectinolytic activity) at 4 degrees C. Selected isolates were able to grow at 2
      degrees C under laboratory-simulated in situ conditions. In all, 106 isolated
      yeasts were identified by MSP-PCR fingerprinting and 26S rRNA gene sequencing of
      the D1/D2 region as belonging to 10 species: Aureobasidium pullulans,
      Cryptococcus gilvescens (over 50% of the total), Cryptococcus terricolus, Mrakia
      gelida, Naganishia globosa, Rhodotorula glacialis, Rhodotorula psychrophenolica,
      Rhodotorula bacarum, Rhodotorula creatinivora and Rhodotorula laryngis. Four
      strains, all belonging to a new yeast species, yet to be described, were also
      isolated.

PMID- 18067578
TI  - Reannotation of hypothetical ORFs in plant pathogen Erwinia carotovora subsp.
      atroseptica SCRI1043.
AB  - Over-annotation of hypothetical ORFs is a common phenomenon in bacterial genomes,
      which necessitates confirming the coding reliability of hypothetical ORFs and
      then predicting their functions. The important plant pathogen Erwinia carotovora
      subsp. atroseptica SCRI1043 (Eca1043) is a typical case because more than a
      quarter of its annotated ORFs are hypothetical. Our analysis focuses on
      annotation of Eca1043 hypothetical ORFs, and comprises two efforts: (a) based on
      the Z-curve method, 49 originally annotated hypothetical ORFs are recognized as
      noncoding, this is further supported by principal components analysis and other
      evidence; and (b) using sequence-alignment tools and some functional resources,
      more than a half of the hypothetical genes were assigned functions. The potential
      functions of 427 hypothetical genes are summarized according to the cluster of
      orthologous groups functional category. Moreover, 114 and 86 hypothetical genes
      are recognized as putative 'membrane proteins' and 'exported proteins',
      respectively. Reannotation of Eca1043 hypothetical ORFs will benefit research
      into the lifestyle, metabolism and pathogenicity of the important plant pathogen.
      Also, our study proffers a model for the reannotation of hypothetical ORFs in
      microbial genomes.

PMID- 18067579
TI  - Redox regulation of the protein tyrosine phosphatase PTP1B in cancer cells.
AB  - The oxidation and inactivation of protein tyrosine phosphatases is one mechanism
      by which reactive oxygen species influence tyrosine phosphorylation-dependent
      signaling events and exert their biological functions. In the present study, we
      determined the redox status of endogenous protein tyrosine phosphatases in HepG2
      and A431 human cancer cells, in which reactive oxygen species are produced
      constitutively. We used mass spectrometry to assess the state of oxidation of the
      catalytic cysteine residue of endogenous PTP1B and show that this residue
      underwent both reversible and irreversible oxidation to high stoichiometry in
      response to intrinsic reactive oxygen species production. In addition, our data
      show that the oxidation of PTP1B is specific to the active site Cys, with the
      other Cys residues in the protein remaining in a reduced state. Treatment of
      these cells with diphenyleniodonium, an inhibitor of NADPH oxidases, decreased
      reactive oxygen species levels. This resulted in inhibition of protein tyrosine
      phosphatase oxidation, concomitant with decreased tyrosine phosphorylation of
      cellular proteins and inhibition of anchorage-independent cell growth. Therefore,
      our data also suggest that the high level of intrinsic reactive oxygen species
      may contribute to the transformed phenotype of HepG2 and A431 cells via
      constitutive inactivation of cellular protein tyrosine phosphatases.

PMID- 18067581
TI  - Signal peptide peptidase and its homologs in Arabidopsis thaliana--plant tissue
      specific expression and distinct subcellular localization.
AB  - Signal peptide peptidase (SPP) is an aspartic proteinase that hydrolyses its
      substrate within the plane of the cellular membrane. In vertebrates, it plays
      crucial roles in life processes such as differentiation, embryogenesis, cell
      signaling and immunological response. We first found SPP in plants. An ortholog
      of human SPP (AtSPP), and its five AtSPP homologs (AtSPPL1-AtSPPL5), were
      searched for in the Arabidopsis database. These clones were grouped into three
      different clusters: AtSPP was grouped with human SPP (HsSPP) orthologs, AtSPPL1
      with the HsSPPL3 family, and AtSPPL2-AtSPPL5 with the group of SPP-like proteins
      of plant origin. AtSPP, AtSPPL1 and AtSPPL2 were examined for their expression
      profiles by in situ hybridization. AtSPP was strongly expressed in both the shoot
      meristem of germinating seeds and the inflorescence meristem at the reproductive
      stage. On the other hand, AtSPPL1 and AtSPPL2 were expressed in the shoot
      meristem of germinating seeds, but at very low levels in the shoot apex at the
      reproductive stage. The subcellular localization of AtSPP, AtSPPL1 and AtSPPL2
      was investigated using green fluorescent protein (GFP) fusion proteins in
      cultured 'Deep' cells. GFP-AtSPP localized to the endoplasmic reticulum (ER), and
      GFP-AtSPPL1 and GFP-AtSPPL2 to the endosomes. These results suggest that AtSPP
      mediates the cleavage of signal peptide in the ER membrane as well as HsSPP does,
      and also that AtSPPL1 and AtSPPL2 located in the endosomes have distinct roles in
      cells.

PMID- 18067580
TI  - Mutational analyses of human eIF5A-1--identification of amino acid residues
      critical for eIF5A activity and hypusine modification.
AB  - The eukaryotic translation initiation factor 5A (eIF5A) is the only protein that
      contains hypusine [Nepsilon-(4-amino-2-hydroxybutyl)lysine], which is required
      for its activity. Hypusine is formed by post-translational modification of one
      specific lysine (Lys50 for human eIF5A) by deoxyhypusine synthase and
      deoxyhypusine hydroxylase. To investigate the features of eIF5A required for its
      activity, we generated 49 mutations in human eIF5A-1, with a single amino acid
      substitution at the highly conserved residues or with N-terminal or C-terminal
      truncations, and tested mutant proteins in complementing the growth of a
      Saccharomyces cerevisiae eIF5A null strain. Growth-supporting activity was
      abolished in only a few mutant eIF5As (K47D, G49A, K50A, K50D, K50I, K50R, G52A
      and K55A), with substitutions at or near the hypusine modification site or with
      truncation of 21 amino acids from either the N-terminus or C-terminus. The
      inactivity of the Lys50 substitution proteins is obviously due to lack of
      deoxyhypusine modification. In contrast, K47D and G49A were effective substrates
      for deoxyhypusine synthase, yet failed to support growth, suggesting critical
      roles of Lys47 and Gly49 in eIF5A activity, possibly in its interaction with
      effector(s). By use of a UBHY-R strain harboring genetically engineered unstable
      eIF5A, we present evidence for the primary function of eIF5A in protein
      synthesis. When selected eIF5A mutant proteins were tested for their activity in
      protein synthesis, a close correlation was observed between their ability to
      enhance protein synthesis and growth, lending further support for a central role
      of eIF5A in translation.

PMID- 18067582
TI  - Novel N,N '-diacyl-1,3-diaminopropyl-2-carbamoyl bivalent cationic lipids for
      gene delivery--synthesis, in vitro transfection activity, and physicochemical
      characterization.
AB  - Novel N,N'-diacyl-1,3-diaminopropyl-2-carbamoyl bivalent cationic lipids were
      synthesized and their physicochemical properties in lamellar assemblies with and
      without plasmid DNA were evaluated to elucidate the structural requirements of
      these double-chained pH-sensitive surfactants for potent non-viral gene delivery
      and expression. The highest in vitro transfection efficacies were induced at +/
      4:1 by the dimyristoyl, dipalmitoyl and dioleoyl derivatives 1,3lb2, 1,3lb3 and
      1,3lb5, respectively, without inclusion of helper lipids. Transfection activities
      were reduced in the presence of either 1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine alone or in combination with cholesterol for all derivatives
      except 1,3lb5, which maintained reporter gene expression levels at +/-4:1 and
      yielded increased lipofection activity at a lower charge ratio of +/-2:1.
      Ethidium bromide displacement indicated efficient plasmid DNA binding and
      compaction by the transfection-competent analogs. Dynamic light-scattering and
      electrophoretic mobility studies revealed lipoplexes of the active lipids with
      large particle sizes (mean diameter>or=500 nm) and zeta potentials with positive
      values (low ionic strength) or below neutrality (high ionic strength). Langmuir
      film balance studies showed high in-plane elasticity of these derivatives in
      isolation. In agreement with the monolayer experiments, fluorescence polarization
      studies verified the fluid nature of the highly transfection-efficient
      amphiphiles, with gel-to-liquid crystalline phase transitions below physiological
      temperature. The active compounds also interacted with endosome-mimicking
      vesicles to a greater extent than the poorly active derivative 1,3lb4, as
      revealed by fluorescence resonance energy transfer experiments. Taken together,
      the results suggest that well-hydrated and highly elastic cationic lipids with
      increased acyl chain fluidity and minimal cytotoxicity elicit high transfection
      activity.

PMID- 18067583
TI  - Effects of replacing active site residues in a cold-active alkaline phosphatase
      with those found in its mesophilic counterpart from Escherichia coli.
AB  - Alkaline phosphatase (AP) from a North Atlantic marine Vibrio bacterium was
      previously characterized as being kinetically cold-adapted. It is still unknown
      whether its characteristics originate locally in the active site or are linked to
      more general structural factors. There are three metal-binding sites in the
      active site of APs, and all three metal ions participate in catalysis. The amino
      acid residues that bind the two zinc ions most commonly present are conserved in
      all known APs. In contrast, two of the residues that bind the third metal ion
      (numbered 153 and 328 in Escherichia coli AP) are different in various APs. This
      may explain their different catalytic efficiencies, as the Mg2+ most often
      present there is important for both structural stability and the reaction
      mechanism. We have mutated these key residues to the corresponding residues in E.
      coli AP to obtain the double mutant Asp116/Lys274, and both single mutants. All
      these mutants displayed reduced substrate affinity and lower overall reaction
      rates. The Lys274 and Asp116/Lys274 mutants also displayed an increase in global
      heat stability, which may be due to the formation of a stabilizing salt bridge.
      Overall, the results show that a single amino acid substitution in the active
      site is sufficient to alter the structural stability of the cold-active Vibrio AP
      both locally and globally, and this influences kinetic properties.

PMID- 18067584
TI  - EspFU, a type III-translocated effector of actin assembly, fosters epithelial
      association and late-stage intestinal colonization by E. coli O157:H7.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 induces filamentous actin-rich
      'pedestals' on intestinal epithelial cells. Pedestal formation in vitro requires
      translocation of bacterial effectors into the host cell, including Tir, an EHEC
      receptor, and EspF(U), which increases the efficiency of actin assembly initiated
      by Tir. While inactivation of espF(U) does not alter colonization in two
      reservoir hosts, we utilized two disease models to explore the significance of
      EspF(U)-promoted actin pedestal formation. EHECDeltaespF(U) efficiently colonized
      the rabbit intestine during co-infection with wild-type EHEC, but co-infection
      studies on cultured cells suggested that EspF(U) produced by wild-type bacteria
      might have rescued the mutant. Significantly, EHECDeltaespF(U) by itself was
      fully capable of establishing colonization at 2 days post inoculation but unlike
      wild type, failed to expand in numbers in the caecum and colon by 7 days. In the
      gnotobiotic piglet model, an espF(U) deletion mutant appeared to generate actin
      pedestals with lower efficiency than wild type. Furthermore, aggregates of the
      mutant occupied a significantly smaller area of the intestinal epithelial surface
      than those of the wild type. Together, these findings suggest that, after initial
      EHEC colonization of the intestinal surface, EspF(U) may stabilize bacterial
      association with the epithelial cytoskeleton and promote expansion beyond initial
      sites of infection.

PMID- 18067585
TI  - Cryptic fragment alpha4 LG4-5 derived from laminin alpha4 chain inhibits de novo
      adipogenesis by modulating the effect of fibroblast growth factor-2.
AB  - Cleavage of the extracellular matrix (ECM) by proteolysis unmasks cryptic sites
      and generates novel fragments with biological activities functionally distinct
      from those of the intact ECM molecule. The laminin G-like (LG)4-5 fragment has
      been shown to be excised from the laminin alpha4 chain in various tissues.
      However, the functional role of this fragment has remained unknown to date. To
      investigate this, we prepared alpha4 LG1-3 and alpha4 LG4-5 fragments by elastase
      digestion of recombinant alpha4 LG1-5, and examined their effects on de novo
      adipogenesis in mice at the site of injection of basement membrane extract
      (Matrigel) and fibroblast growth factor (FGF)-2. Although the addition of whole
      alpha4 LG1-5 suppressed adipogenesis to some extent, the alpha4 LG4-5 fragment
      could strongly suppress adipogenesis at a concentration of less than 20 nm.
      Addition of the alpha4 LG4 module, which contains a heparin-binding region, had a
      suppressive effect, but this was lost in mutants with reduced heparin-binding
      activity. In addition, antibodies against the extracellular domain of syndecan-2
      and -4, which are known receptors for the alpha4 LG4 module, suppressed
      adipogenesis. Thus, these results suggest that the cryptic alpha4 LG4-5 fragment
      derived from the laminin alpha4 chain inhibits de novo adipogenesis by modulating
      the effect of FGF-2 through syndecans.

PMID- 18067586
TI  - R-spondin2 expression in the apical ectodermal ridge is essential for outgrowth
      and patterning in mouse limb development.
AB  - Mouse R-spondin2 (Rspo2) is a member of the R-spondin protein family, which is
      characterized by furin-like cysteine-rich domains and a thrombospondin type 1
      repeat. R-spondin is a secreted molecule that activates Wnt/beta-catenin
      signaling. Rspo2-deficient mice were generated to investigate the function of
      mouse Rspo2 during embryonic development. The homozygous mutant forelimb showed
      defects in distal phalanges and nail structures, and the digits were anomalous in
      shape. The homozygous mutant hindlimb showed more severe malformations, including
      lack of digits and zeugopod components. Rspo2 is expressed in the apical
      ectodermal ridge (AER) of the developing limb. Fgf8 expression in the AER was
      significantly lower in the homozygous mutant forelimb than in the wild-type
      forelimb and it was disturbed along the dorsoventral axis. In the homozygous
      mutant hindlimb, Fgf8 and Fgf4 expression in the posterior AER and Sonic hedgehog
      expression in the zone of polarizing activity (ZPA) were reduced. The homozygous
      mutant hindlimb also showed expansion of Wnt7a expression in the dorsal ectoderm
      toward the ventral side. This study shows that Rspo2 is critical for maintenance
      of the AER and for growth and patterning in limb development.

PMID- 18067588
TI  - FMRFamide modulates outward potassium currents in mouse olfactory sensory
      neurons.
AB  - 1. The olfactory system can detect the presence of low concentrations of odourant
      molecules and discriminate even slight differences among molecules with a very
      similar chemical structure. The detection and discrimination of odourants are
      correlated with the electrophysiology of the olfactory sensory neurons. To get a
      better understanding of the molecular mechanisms of olfactory transduction, it is
      therefore of considerable importance to obtain electrophysiological recordings of
      olfactory sensory neurons. FMRFamide (Phe-Met-Arg-Phe-NH(2)), secreted from the
      nerve terminals of the nasal cavity, has been suggested to act as a
      neurotransmitter or neuromodulator, playing an important role in modulating the
      activity of olfactory receptor neurons. Its effects on voltage-dependent
      potassium currents in the mouse olfactory sensory neurons were investigated in
      the present study using the whole-cell patch-clamp technique. 2. Olfactory
      sensory neurons were isolated from the Kunming Mouse (KM) mouse olfactory
      epithelium. Different protocols were applied to obtain delayed-rectifier
      potassium current (I(K)) and fast transient potassium current (I(A)). The effects
      of FMRFamide on the outward potassium currents, including I(K) and I(A), in mouse
      olfactory sensory neurons were investigated. 3. We found that FMRFamide (5
      micromol/L) increased the magnitude of I(K). However no effect on I(A) was
      observed. The activation dynamics of both currents were not changed by FMRFamide.
      4. In conclusion, FMRFamide may play a role in the modulation of peripheral
      olfactory signals by regulating I(K). This modulation may shorten the phase of
      the fast repolarization of the action potential in mouse olfactory sensory
      neurons and increase the excitability of the neuronal membrane.

PMID- 18067587
TI  - Isolation and characterization of Kit-independent melanocyte precursors induced
      in the skin of Steel factor transgenic mice.
AB  - Steel factor (SLF, also called KIT-ligand, mast cell growth factor, or stem cell
      factor) acting through the tyrosine kinase receptor KIT is thought to be
      indispensable for the early phase of melanocyte development both in vivo and in
      vitro. In the present study, Kit-independent precursor cells were generated in
      mice expressing exogenous SLF in their skin keratinocytes and were detected as
      pigmented spots after administration of Kit function-blocking antibody. We
      successfully purified these precursor or stem cells as Kit+CD45- cells by flow
      cytometry. The purified cells showed normal but delayed differentiation into
      mature melanocytes, indicating the immature nature of Kit-independent precursors.
      The Kit-independent interfollicular population generated in SLF transgenic mice
      was suggested to be the counterpart of the follicular melanocyte stem cell based
      on the Kit-independent nature for their survival.

PMID- 18067589
TI  - Arachidonic acid metabolism in glucocorticoid-induced hypertension.
AB  - 1. Products of metabolism of arachidonic acid, such as 20-hydroxyeicosatetraenoic
      acid (20-HETE), thromboxane A(2) (TXA(2)) and prostaglandin I(2) (PGI(2)),
      regulate vascular tone. Among them, 20-HETE is a potent constrictor in small
      arteries that also has natriuretic properties. The present study investigated
      changes in urinary concentrations of 20-HETE and metabolites of TXA(2) and PGI(2)
      in glucocorticoid-hypertension in rats, a sodium-independent model. 2. Male
      Sprague-Dawley rats were treated with saline, adrenocorticotrophic hormone (ACTH;
      0.2 mg/kg) or dexamethasone (20 microg/kg) by daily s.c. injection for 12 days.
      Systolic blood pressure (SBP) was measured using the tail-cuff method. Metabolic
      cages were used for 24 h urine collection. Thymus weight and urinary
      concentrations of 20-HETE, TXA(2) and PGI(2) were determined. 3. In the present
      study, SBP was increased by both ACTH (from 102 +/- 2 to 134 +/- 7 mmHg; n = 10;
      P < 0.01) and dexamethasone (from 106 +/- 5 to 122 +/- 4 mmHg; n = 10; P < 0.01).
      Thymus weight, a marker for glucocorticoid activity, was significantly decreased
      by both ACTH and dexamethasone (56 +/- 9 and 76 +/- 5 mg/100 g bodyweight,
      respectively; n = 10; P' < 0.01) compared with the saline control (151 +/- 5
      mg/100 g bodyweight; n = 20). Urinary 20-HETE excretion was increased by ACTH
      (501 +/- 115 pmol/g creatinine; n = 10; P' < 0.05) but not by dexamethasone (126
      +/- 13 pmol/g creatinine; n = 10) compared with the saline control (219 +/- 54
      pmol/g creatinine; n = 20). Neither ACTH nor dexamethasone affected urinary
      excretion of TXB(2) or PGI(2) compared with the saline control. 4. In conclusion,
      ACTH but not dexamethasone increased urinary 20-HETE excretion in male Sprague
      Dawley rats. Urinary concentrations of the metabolites TXB(2) and PGI(2) were
      unchanged in both models of glucocorticoid-hypertension. The vasoconstrictor 20
      HETE may play a role in the genesis of ACTH-induced hypertension.

PMID- 18067590
TI  - Effects of volume depletion and NaHCO3 loading on the expression of Na+/H+
      exchanger isoform 3, Na+: HCO3- cotransporter type 1 and nitric oxide synthase in
      rat kidney.
AB  - 1. The effects of volume depletion and NaHCO(3) loading on the expression of
      Na(+)/H(+) exchanger isoform 3 (NHE3), Na(+) : HCO(3)(-) cotransporter type 1
      (NBC1) and neuronal (n) and inducible (i) isoforms of nitric oxide synthase (NOS)
      were determined in rat kidney. 2. Adult male Sprague-Dawley rats were used. Rats
      were divided into four groups: (i) euvolaemic (EC); (ii) hypovolaemic (HC); (iii)
      euvolaemia with NaHCO(3) loading (EB); and (iv) hypovolaemia with NaHCO(3)
      loading (HB). The expression of NHE3, NBC1, nNOS and iNOS proteins was determined
      in the cortex of the kidney by immunoblotting and immunohistochemistry. Tissue
      content of nitric oxide (NO) metabolites (NO(x)) were also determined in the
      cortex using a colourimetric assay. 3. Compared with the EC group, the expression
      of NHE3 and NBC1 was increased in the HC group and decreased in the EB group.
      Comparing the EB and HB groups, the expression of NHE3 and NBC1 was higher in the
      latter group. The expression of NHE3 was decreased and that of NBC1 was increased
      in the HB group compared with the HC group. The NO(x) content and nNOS expression
      were decreased in the hypovolaemic (HC) and NaHCO(3)-loaded (EB and HB) rats.
      Moreover, the expression of iNOS was decreased in the HB group compared with the
      other groups. 4. An altered volume status and NaHCO(3) loading may affect the
      regulation of NHE3 and NBC1 in the kidney and the endogenous NO system may play a
      role in the observed effects.

PMID- 18067591
TI  - CD36 mRNA expression is increased in CD14+ monocytes of patients with coronary
      heart disease.
AB  - 1. Blood-derived monocytes/macrophages within the intima of the arterial wall are
      the main source of inflammatory cytokines and factors contributing to lesion
      growth, plaque instability and thrombotic events. In the present study, we
      assessed the hypothesis that mRNA expression levels of candidate genes of
      atherosclerosis in circulating CD14(+) blood monocytes are associated with
      coronary heart disease (CHD). 2. We investigated mRNA expression levels using
      reverse transcription-polymerase chain reaction of genes involved in cholesterol
      uptake (macrophage scavenger receptor (MSR1), scavenger receptor class B member 1
      (SRB1), lectin-like oxidized low-density lipoprotein (LDL) receptor 1 (LOX1),
      CD36, LDL receptor (LDLR)), reverse cholesterol transport (apolipoprotein E
      (ApoE), ATP-binding cassette sub-family A member 1 (ABCA1)) and inflammation
      (tumour necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha
      (MIP-1alpha), interleukin-6 (IL-6), tissue factor) in CD14(+) monocytes from 119
      consecutively recruited patients and found that median CD36 mRNA expression
      levels were significantly increased in patients with CHD compared with controls
      (111 x 10(3) vs 96 x 10(3) copies/10(6) copies beta-actin, respectively; n = 79
      and 40, respectively; P < 0.05), despite a high interindividual variability in
      gene expression. 3. A common T --> C polymorphism (rs2151916) located only 14 bp
      upstream of the upstream transcriptional start site did not influence CD36
      expression. 4. Expression levels of the other candidate genes investigated in the
      present study did not show any statistically significant differences between
      patients with CHD and controls. 5. We conclude that CD36 mRNA expression is
      significantly increased in patients with CHD and may serve as an indicator of CHD
      burden.

PMID- 18067592
TI  - Forebrain osmotic regulation of the sympathetic nervous system.
AB  - 1. Accumulating evidence in both humans and animals indicates that acute
      increases in plasma osmolality elevate sympathetic nerve activity (SNA). In
      addition, plasma hyperosmolality (or hypernatraemia) can produce sustained
      increases in SNA and arterial blood pressure (ABP) through stimulation of
      forebrain osmoreceptors. 2. Although an abundance of information exists regarding
      the osmoregulatory circuits for thirst and secretion of antidiuretic hormone,
      much less is known about those pathways and synaptic mechanisms linking osmotic
      perturbations and SNA. To date, the available evidence suggests that
      osmosensitive sites within the forebrain lamina terminalis, such as the organum
      vasculosum of the lamina terminalis, are key elements that link plasma
      hypertonicity to elevated SNA. 3. The major efferent target of osmosensitive
      regions in the forebrain lamina terminalis is the hypothalamic paraventricular
      nucleus (PVH). Evidence from a number of studies indicates that the PVH
      contributes to both acute and chronic osmotically driven increases in SNA. In
      turn, PVH neurons increase SNA through a direct vasopressinergic spinal pathway
      and/or a glutamatergic pathway to bulbospinal sympathetic neurons of the rostral
      ventrolateral medulla. 4. Future studies are needed to: (i) define the
      contribution of various osmosensitive regions of the forebrain lamina terminalis
      to acute and chronic osmotically driven increases in SNA; (ii) identify the
      cellular mechanisms and neural circuitry linking plasma osmolality and SNA; and
      (iii) define whether such mechanisms contribute to elevated SNA in salt-sensitive
      hypertension.

PMID- 18067593
TI  - Optical imaging analysis of neural circuit formation in the embryonic brain.
AB  - 1. Multiple-site optical recording with the voltage-sensitive absorption dye
      NK2761 was used to investigate functiogenesis of the neural circuits in the
      embryonic central nervous system (CNS). In the present review, we emphasize the
      functional development of glossopharyngeal nerve (N. IX)- and vagus nerve (N. X)
      related neural circuits in the embryonic chick brainstem. 2. In the nucleus
      tractus solitarius (NTS), glutamatergic excitatory post-synaptic potentials
      (EPSPs) evoked by stimulation of N. IX/N. X were first detected at Embryonic Day
      (E) 7, when morphological differentiation of pre- and post-synaptic neurons is
      incomplete. The removal of extracellular Mg(2+) elicited small EPSPs at E6,
      suggesting that synaptic function mediated by N-methyl-d-aspartate (NMDA)
      receptors (glutamatergic receptors) is latently generated 1 day before the
      expression of glutamatergic EPSPs. In the nucleus of the glossopharyngeal nerve
      and the dorsal motor nucleus of the vagus nerve, action potentials were detected
      from E3.5 and E4, respectively. Similar chronological sequences were observed in
      the rat embryo and in other cranial nerve-related nuclei and were used to
      construct basic profiles of embryonic EPSPs in the vertebrate CNS. 3. We further
      investigated the development of the secondary synaptic pathways from the NTS to
      higher centres and found that neuronal circuits from the NTS are already
      generated when the primary afferents form functional synapses with NTS neurons.
      4. A widely spreading depolarization wave was found in the embryonic CNS. This
      wave was triggered by multisensory inputs and spontaneous activities and was
      suggested to be mediated by a dual network of chemical synapses and gap
      junctions. It was also accompanied by a Ca(2+) wave, indicating its nurturing
      effects on CNS development.

PMID- 18067594
TI  - Central osmoregulatory influences on thermoregulation.
AB  - 1. Many mammals maintain a constant core body temperature in the face of a heat
      load by using evaporative cooling responses, such as sweating, panting and
      spreading of saliva. These cooling mechanisms incur a body fluid deficit if the
      fluid lost as sweat, saliva or respiratory moisture is not replaced by the
      ingestion of water; body fluid hypertonicity and hypovolaemia result. 2. Evidence
      in several mammals shows that, as they become dehydrated, evaporative cooling
      mechanisms such as sweating and panting are inhibited so that further fluid loss
      from the body is reduced. As a result, core temperature in the dehydrated animal
      is maintained at a higher than normal level. 3. Increasing the osmotic pressure
      of plasma has an inhibitory effect on panting and sweating in mammals. It has
      been proposed that osmoreceptors mediate these inhibitory influences of plasma
      hypertonicity on sweating and panting. 4. The suppression of panting in
      dehydrated sheep is mediated by cerebral osmoreceptors that are probably located
      in the lamina terminalis. We speculate that osmoreceptors in the lamina
      terminalis may also influence thermoregulatory sweating. 5. When dehydrated
      animals drink water, sweating and panting resume rapidly before water has been
      absorbed from the gut. It is likely that the act of drinking initiates a reflex
      that can override the osmoreceptor inhibition of panting, resulting in core
      temperature falling back quickly to a normal level.

PMID- 18067595
TI  - Abnormalities of sarcoplasmic reticulum Ca2+ mobilization in aortic smooth muscle
      cells from streptozotocin-induced diabetic rats.
AB  - 1. Previously, we found that contractions in response to receptor-dependent (i.e.
      a(1)-adrenoceptor agonist phenylephrine) and -independent (i.e. cyclopiazonic
      acid) stimuli are decreased in rat aorta during late diabetes. The aim of the
      present study was to further investigate the changes of intracellular Ca(2+)
      homeostasis in diabetic aortic smooth muscle cells. Functional changes of
      inositol 1,4,5-trisphosphate (IP(3))- and ryanodine-sensitive Ca(2+) stores of
      the sarcoplasmic reticulum (SR) were evaluated using Fluo-3 acetoxymethyl ester
      fluorescence, western blot and organ bath techniques. 2. In aortic smooth muscle
      cells from diabetic rats, the Ca(2+) release and Ca(2+) influx caused by both 10
      mmol/L phenylephrine (depletion of IP(3)-sensitive Ca(2+) stores) and 1 mmol/L
      ryanodine (depletion of ryanodine-sensitive Ca(2+) stores) were both
      significantly decreased compared with control. Moreover, protein expression
      levels of IP(3) (260 kDa) and ryanodine receptors (500 kDa) were reduced by 31.8
      +/- 7.7 and 69.2 +/- 8.4%, respectively, in aortas from diabetic rats compared
      with those from control rats. 3. In diabetic rat aorta, phenylephrine-induced
      contractility was decreased to approximately two-thirds of that in controls,
      whereas ryanodine alone did not cause obvious contraction in aortas from either
      control or diabetic rats. 4. The present results suggest that the hyporeactivity
      of aortic smooth muscle to vasoconstrictors in diabetes results mainly from
      changes to the IP(3)-sensitive Ca(2+) release pathway. The SR Ca(2+) signalling
      pathway plays a crucial role in the development of diabetic vascular
      complications.

PMID- 18067596
TI  - Elevated levels of circulating cortisol in young normotensive adult men with a
      family history of hypertension.
AB  - 1. Differences in blood lipids, glucose, insulin, amylin, adrenocorticotropic
      hormone (ACTH), cortisol, aldosterone, angiotensin II, metabolites of nitric
      oxide (nitrate, nitrite), asymmetric dimethyl arginine, endothelial leucocyte
      adhesion molecule-1, vascular cell adhesion molecule-1, C-reactive protein,
      homocysteine and oxidative status (urate, vitamin A, vitamin E, beta-carotene and
      total anti-oxidant capacity) were investigated in men (aged 18-25 years) with (+)
      or without (-) a family history (FH) of hypertension. 2. In the present study,
      FH+ was defined as having at least one parent or grandparent taking medication
      for hypertension. Blood (60 mL) was sampled (0800-1000 hours) from a cannulated
      forearm vein after an overnight fast and 24 h abstinence from caffeine-containing
      products and alcohol. 3. Comparing FH+ with FH-, systolic blood pressure (124 +/-
      1 vs 117 + 3 mmHg, respectively; n = 50 and 14, respectively; P < 0.05) and
      plasma cortisol (377 +/- 23 vs 298 +/- 24 nmol/L, respectively; n = 43 and 12,
      respectively; P < 0.05) were found to be significantly higher in the former
      group. 4. No significant difference was found between the two groups for body
      mass index, resting heart rate, diastolic and mean blood pressures or any of the
      biochemical measures studied. 5. A significant correlation was found between
      cortisol and ACTH (r = 0.73). No correlation was found between cortisol and any
      other parameter measured. 6. These data indicate that elevated cortisol levels
      are characteristic of young lean normotensive FH+ men. The future impact of this
      on their vascular health and hypertension remains to be determined.

PMID- 18067597
TI  - A systematic review of the 5-year survival and complication rates of implant
      supported single crowns.
AB  - OBJECTIVES: The objective of this systematic review was to assess the 5-year
      survival of implant-supported single crowns (SCs) and to describe the incidence
      of biological and technical complications. METHODS: An electronic MEDLINE search
      complemented by manual searching was conducted to identify prospective and
      retrospective cohort studies on SCs with a mean follow-up time of at least 5
      years. Failure and complication rates were analyzed using random-effects
      Poisson's regression models to obtain summary estimates of 5-year proportions.
      RESULTS: Twenty-six studies from an initial yield of 3601 titles were finally
      selected and data were extracted. In a meta-analysis of these studies, survival
      of implants supporting SCs was 96.8% [95% confidence interval (CI): 95.9-97.6%]
      after 5 years. The survival rate of SCs supported by implants was 94.5% (95% CI:
      92.5-95.9%) after 5 years of function. The survival rate of metal-ceramic crowns,
      95.4% (95% CI: 93.6-96.7%), was significantly (P=0.005) higher than the survival
      rate, 91.2% (95% CI: 86.8-94.2%), of all-ceramic crowns. Peri-implantitis and
      soft tissue complications occurred adjacent to 9.7% of the SCs and 6.3% of the
      implants had bone loss exceeding 2 mm over the 5-year observation period. The
      cumulative incidence of implant fractures after 5 years was 0.14%. After 5 years,
      the cumulative incidence of screw or abutment loosening was 12.7% and 0.35% for
      screw or abutment fracture. For supra-structure-related complications, the
      cumulative incidence of ceramic or veneer fractures was 4.5%. CONCLUSION: It can
      be concluded that after an observation period of 5 years, high survival rates for
      implants and implant-supported SCs can be expected. However, biological and
      particularly technical complications are frequent.

PMID- 18067598
TI  - Early loading of sandblasted and acid-etched implants: a randomized-controlled
      double-blind split-mouth study. Five-year results.
AB  - OBJECTIVES: The aim of the present split-mouth study is to assess the peri
      implant conditions around early-loaded sandblasted and acid-etched (SLA)
      implants, 5 years after abutment connection and to compare, in the same patients,
      the results obtained with a standard protocol using identical implants with a TPS
      surface. MATERIAL AND METHODS: Surgical procedure was performed by the same
      operator and was identical at test (SLA) and control (TPS) sites, in 32 healthy
      patients. Abutment connection was carried out at 35 N cm 6 weeks postsurgery for
      test sites and 12 weeks for the controls. Patients were seen regularly, for
      control and professional cleaning. At 60 months, clinical measures and
      radiographic bone changes were recorded by the same operator, blind to the type
      of surface of the implant, on 27 patients, as five patients were lost to follow
      up. RESULTS: A total number of 106 implants were examined. No implant was lost.
      No significant differences were found with respect to the presence of plaque
      [modified plaque index (mPI) 0.27+/-0.56 vs. 0.32+/-0.54], bleeding on probing
      (29% vs. 32%), mean pocket depth (3.2+/-1 vs. 3.2+/-1 mm) or mean marginal bone
      loss (0.32+/-1.04 vs. 0.44+/-1.12 mm) between test and control. Four implants
      that presented 'spinning' at the time of abutment connection presented no
      significant differences from the rest of the test sites. CONCLUSION: The results
      of this prospective study confirm that SLA implants, under defined conditions,
      are suitable for early loading at 6 weeks in both the mandible and the maxilla.
      Limited implant spinning, occasionally found at abutment connection, produces no
      detrimental effect on the clinical outcome when properly handled.

PMID- 18067599
TI  - Parameters of resonance frequency measurement values: a retrospective study of
      385 ITI dental implants.
AB  - OBJECTIVES: There is no proven clinical tool to evaluate the amount of
      osseointegration and stability around dental implants. Therefore, the aim of this
      retrospective clinical study was to evaluate resonance frequency analysis values
      of 385 ITI solid screw implants. MATERIAL AND METHODS: Both at implant placement
      and after healing, implant stability quotients (ISQs) were determined. For
      statistical analysis, Pearson's correlation coefficients, Welch's two-sample t
      tests and paired samples t-tests were computed at a level of significance of
      alpha=0.05. RESULTS: ISQ values ranged from 39 to 86 at implant placement and
      from 35 to 89 after healing, showing a significant increase. The highest ISQ
      values at both stages were obtained in the posterior mandible (P < or = 0.002).
      After healing, ISQ values in the anterior mandible were significantly higher than
      in the anterior maxilla (P=0.005). Implant length had a significant influence on
      ISQ in the anterior mandible (P=0) at insertion and in the anterior (P=0.005) and
      posterior mandible (P=0.036) after healing. Implant diameter and ISQ at insertion
      correlated in the anterior mandible (P=0.037). After healing, a significant
      influence was found for all regions, except the posterior maxilla (P=0.795). With
      the exception of the anterior maxilla (P=0.542), ISQ at placement had a
      significant influence on ISQ after healing. In the anterior maxilla (P=0.002) and
      in the posterior mandible (P=0.007), healing time significantly influenced ISQ
      after healing. CONCLUSIONS: It appears that only repeated ISQ measurements of a
      specific implant have some diagnostic benefit, although the parameters
      influencing the absolute values still remain unclear.

PMID- 18067600
TI  - Implant stability during osseointegration in irradiated and non-irradiated
      minipig alveolar bone: an experimental study.
AB  - OBJECTIVES: Primary implant stability is related to local bone density. After
      insertion of an implant, implant stability is subject to changes due to bone
      remodeling. In patients who have undergone radiotherapy in the head and neck
      region, implant stability is impaired because irradiation reduces bone vitality.
      The current study was designed to monitor and test implant stability immediately
      after implant placement and during osseointegration in irradiated and non
      irradiated minipig alveolar bone. MATERIALS AND METHODS: All maxillary and
      mandibular premolars and molars of six adult Gottingen minipigs were extracted.
      The maxilla and mandible of three minipigs received three irradiation exposures
      at a total dose of 24 Gy. After irradiation, five initial implant holes were
      drilled in the residual alveolar ridge of each edentulous site. In order to
      assess bone vascularity, laser Doppler flowmetry recordings were carried out in
      the initial holes. A total of 120 implants were placed in the six minipigs.
      Subsequently, and at 8, 16, and 24 weeks after implant placement, implant
      stability was recorded by resonance frequency analysis (RFA). RFA values were
      expressed as an implant stability quotient (ISQ). RESULTS: ISQ values recorded
      immediately after implant placement showed no differences between irradiated and
      non-irradiated minipigs. Repeated measurements at the four recording moments
      showed a decrease of ISQ values in all minipigs, being more pronounced in
      irradiated bone, when compared with non-irradiated bone. The results at the third
      and fourth recording moments showed a stabilization or even a slight increase of
      ISQ values. CONCLUSIONS: The results document the negative effect of irradiation
      on bone vascularity and hence on implant stability.

PMID- 18067601
TI  - Effect of platelet-rich plasma on the early bone formation around Ca-P-coated and
      non-coated oral implants in cortical bone.
AB  - OBJECTIVES: The purpose of the present study was to investigate the effect of
      local application of platelet-rich plasma (PRP) on the early healing of cortical
      bone around Ti implants with two different surface configurations. MATERIAL AND
      METHODS: Six goats were used in this study. PRP fractions were obtained from a
      venous blood sample of the goats and administered immediately before implant
      insertion. PRP was applied via gel preparation and installation of the gel into
      the implant site, or via dipping of the implants in PRP fraction before
      insertion. A total of 36 implants (18 non-coated and 18 Ca-P-coated) were placed
      into the tibial cortical bone. The animals were sacrificed at 6 weeks after
      implantation and implants with surrounding tissue were prepared for histological
      examination. Histomorphometrical variables like the percentage of implant surface
      with direct bone-implant contact and the percentage of new and old bone adjacent
      to the implant were evaluated. RESULTS: More interfacial bone-to-implant contact
      was observed for all the three groups of Ca-P-coated implants and the Ti/PRP
      liquid group. All groups revealed similar percentages of old and new bone
      adjacent to the implant. CONCLUSIONS: It was concluded that the additional use of
      PRP did not have any effect on the early cortical bone response to the Ca-P
      coated implants, while PRP in a liquid form showed a tendency to increase bone
      apposition to roughened titanium implants.

PMID- 18067602
TI  - Bone morphogenetic protein-2 enhances bone formation when delivered by a
      synthetic matrix containing hydroxyapatite/tricalciumphosphate.
AB  - PURPOSE: The aim of the present study was to test whether or not a synthetic
      matrix consisting of a polyethylene glycol (PEG) hydrogel containing recombinant
      human bone morphogenetic protein-2 (rhBMP-2) combined with grafting materials
      enhances bone regeneration compared with grafting alone or empty control sites.
      MATERIAL AND METHODS: In each of 10 rabbits, four titanium cylinders were screwed
      in perforated slits made in the external cortical bones of the calvaria. The
      following four treatment modalities were randomly allocated: (1) empty control,
      (2) a combination of a PEG matrix and hydroxyapatite/tricalciumphosphate (HA/TCP)
      granules and a combination of a PEG matrix containing either 10 microg/ml (3) or
      30 microg/ml (4) of BMP-2 and HA/TCP granules. After 8 weeks, the animals were
      sacrificed and ground sections were obtained for histological analysis. For
      statistical analysis repeated measures ANOVA and subsequent pairwise Student's t
      test were applied (P<0.01). RESULTS: Histomorphometric analysis showed an average
      area fraction of newly formed bone of 13.96+/-5.98% for the empty control,
      15.16+/-7.95% for the PEG and HA/TCP group, 26.32+/-8.56% for the group
      containing 10 mug rhBMP-2/ml, and 30.15+/-7.63% for the group containing 30
      microg rhBMP-2/ml. Statistical analysis revealed significantly more newly formed
      bone in the two rhBMP-2 groups compared with the PEG and HA/TCP group and with
      the empty control. Regarding the surface fraction of the HA/TCP graft particles
      covered with newly formed bone the addition of rhBMP-2 revealed a more than two
      fold increase compared with cylinders containing HA/TCP granules without rhBMP-2.
      This difference reached statistical significance. CONCLUSIONS: It is concluded
      that rhBMP-2 significantly enhances bone regeneration in rabbits when delivered
      by a synthetic matrix containing HA/TCP. This synthetic PEG matrix containing
      HA/TCP granules apparently fulfills a number of criteria required for an ideal
      carrier system for rhBMP-2.

PMID- 18067603
TI  - Different effects of oral contraceptives containing different progestogens on
      protein S and tissue factor pathway inhibitor.
AB  - BACKGROUND: Oral contraceptives (OC) containing different types of progestogens
      induce different sensitivities to activated protein C (APC) measured with the
      thrombin generation-based APC-resistance test. These differences in APC
      resistance may be the biological explanation for the differences in thrombotic
      risk of the various pills. The mechanistic basis of APC resistance observed in OC
      users is unknown. Our objective was to study the effect of OC on the two main
      determinants of the APC-resistance test, free protein S and free tissue factor
      pathway inhibitor (TFPI). PATIENTS/METHODS: We measured free protein S and free
      TFPI in 156 users of various types of OC. RESULTS: Users of desogestrel
      containing OC, known to double the risk of thrombosis compared with
      levonorgestrel-containing OC, had lower free protein S (24 vs. 33 U dL(-1)) and
      TFPI free antigen (2.9 vs. 3.6 ng mL(-1)) levels than users of OC containing
      levonorgestrel. Women using cyproterone acetate-containing OC, known to confer a
      high thrombotic risk, had the lowest free protein S (19 U dL(-1)) and free TPFI
      antigen (2.5 ng mL(-1)) levels. Users of OC containing drospirenone had lower
      free protein S (23 U dL(-1)) and TFPI antigen levels (3.2 ng mL(-1)) than users
      of levonorgestrel-containing OC. Low free protein S and low free TFPI antigen
      levels were associated with an increased resistance to APC, an established risk
      factor for thrombosis. CONCLUSIONS: This study observed that the differences in
      APC resistance induced by OC containing different progestogens can at least in
      part be explained by different effects of OC on free protein S and TFPI.

PMID- 18067604
TI  - Invitation to a debate on the serological criteria that define the
      antiphospholipid syndrome.

PMID- 18067606
TI  - Reactive oxygen species are the major antibacterials against Salmonella
      Typhimurium purine auxotrophs in the phagosome of RAW 264.7 cells.
AB  - Intramacrophage survival appears to be a pathogenic trait common to Salmonellae
      and definition of the metabolic requirements of Salmonella within macrophages
      might provide opportunities for novel therapeutic interventions. We show that
      loss of PurG function in Salmonella enterica serovar Typhimurium SL1344 leads to
      death of the bacterium in RAW264.7 cells, which was due to unavailability of
      purine nucleotides but not thiamine in the phagosome of RAW264.7 cells.
      Phagosomal escape of purG mutant restored growth, suggesting that the phagosomal
      environment, but not the cytosol, is toxic to Salmonella purine auxotrophs. NADPH
      oxidase inhibition restored the growth of purG mutant in RAW264.7 cells, implying
      that the Salmonella-containing vacuole acquires reactive oxygen species (ROS)
      that are lethal to purine auxotrophs. Under purine limiting conditions, purG
      mutant was unable to repair the damage caused by hydrogen peroxide or UV
      irradiation, suggesting that ROS-mediated DNA damage may have been responsible
      for the attenuated phenotype of purG mutant in RAW264.7 cells and in mice. These
      studies highlight the possibility of utilizing the Salmonella purine nucleotide
      biosynthetic pathway as a prospective therapeutic target and also underline the
      importance of metabolic pathways in assembling a comprehensive understanding of
      the host-pathogen interactions inside phagocytic cells.

PMID- 18067608
TI  - A bacterial pore-forming toxin forms aggregates in cells that resemble those
      associated with neurodegenerative diseases.
AB  - Listeria monocytogenes is a bacterial, facultative intracellular pathogen, which
      secretes a pore-forming toxin called listeriolysin O (LLO). LLO mediates the
      dissolution of the phagosomal membrane allowing L. monocytogenes to reach and
      grow in the host cytosolic compartment. In this study we report the localization
      of LLO secreted in infected cells. We described that LLO (i) forms small
      perinuclear aggregates, (ii) accumulates in large autophagosome-like structures
      and (iii) sequesters to large protein aggregates. The formation of protein
      aggregates required full LLO activity. Further characterization of protein
      aggregates indicated that they not only contained the active form of LLO but also
      polyubiquitinated proteins and p62, which are both common components of protein
      aggregates found in neurological diseases. Hence, a protein of bacterial origin
      could potentially follow the same fate as a toxic protein associated with
      neurodegenerative disease.

PMID- 18067607
TI  - OipA plays a role in Helicobacter pylori-induced focal adhesion kinase activation
      and cytoskeletal re-organization.
AB  - The initial signalling events leading to Helicobacter pylori infection associated
      changes in motility, cytoskeletal reorganization and elongation of gastric
      epithelial cells remain poorly understood. Because focal adhesion kinase (FAK) is
      known to play important roles in regulating actin cytoskeletal organization and
      cell motility we examined the effect of H. pylori in gastric epithelial cells co
      cultured with H. pylori or its isogenic cag pathogenicity island (PAI) or oipA
      mutants. H. pylori induced FAK phosphorylation at distinct tyrosine residues in a
      dose- and time-dependent manner. Autophosphorylation of FAK Y397 was followed by
      phosphorylation of Src Y418 and resulted in phosphorylation of the five remaining
      FAK tyrosine sites. Phosphorylated FAK and Src activated Erk and induced actin
      stress fibre formation. FAK knock-down by FAK-siRNA inhibited H. pylori-mediated
      Erk phosphorylation and abolished stress fibre formation. Infection with oipA
      mutants reduced phosphorylation of Y397, Y576, Y577, Y861 and Y925, inhibited
      stress fibre formation and altered cell morphology. cag PAI mutants reduced
      phosphorylation of only FAK Y407 and had less effect on stress fibre formation
      than oipA mutants. We propose that activation of FAK and Src are responsible for
      H. pylori-induced induction of signalling pathways resulting in the changes in
      cell phenotype important for pathogenesis.

PMID- 18067609
TI  - Potential dissemination of Bacillus anthracis utilizing human lung epithelial
      cells.
AB  - Dissemination of Bacillus anthracis spores from the lung is a critical early
      event in the establishment of inhalational anthrax. We recently reported that B.
      anthracis could adhere to and be internalized by cultured intestinal epithelial
      and fibroblast cells. Here, using gentamicin protection assays and/or electron
      microscopy, we found that Sterne strain 7702 spores were able to adhere to and
      subsequently be internalized by polarized A549 cells and primary human small
      airway epithelial cells. We showed for the first time that internalized spores
      were able to survive and that spores could translocate across an A549 cell
      barrier from the apical side to the basolateral side without disrupting the
      barrier integrity, suggesting a transcellular route. In addition, dormant spores
      of fully virulent Ames and UT500 strains were able to adhere to A549 cells at a
      frequency similar to that of 7702, whereas the capsule in germinated Ames and
      UT500 spores prevented adherence. Fluorescence microscopy also revealed that
      dormant Ames spores were internalized at a frequency similar to that of 7702.
      These findings highlight the possibility of a novel route of dissemination in
      which B. anthracis utilizes epithelial cells of the lung. The implications of
      these results to B. anthracis pathogenesis are discussed.

PMID- 18067610
TI  - The Outcomes Measures Program: what's in it for you?

PMID- 18067611
TI  - Effects of intramuscular administration of acepromazine on palmar digital blood
      flow, palmar digital arterial pressure, transverse facial arterial pressure, and
      packed cell volume in clinically healthy, conscious horses.
AB  - OBJECTIVE: To determine the magnitude and duration of effects of acepromazine
      administered intramuscularly (IM) on digital and systemic hemodynamic variables
      in clinically healthy horses. STUDY DESIGN: Experimental study. ANIMALS: Healthy
      adult horses (n=12). Methods- An ultrasonic Doppler flow probe was surgically
      implanted around the medial palmar digital artery before the study. Catheters
      were inserted in the transverse facial artery, lateral palmar digital artery, and
      jugular vein. A treatment group (n=6) was administered 0.04 mg/kg body weight of
      acepromazine IM; control horses (n=6) were administered an equivalent volume of
      saline IM. Palmar digital blood flow, and digital and facial arterial pressures
      were measured at baseline and for 6 hours after administration. Venous blood was
      collected for measurement of packed cell volume (PCV). RESULTS: Horses
      administered acepromazine had significantly lower facial arterial pressure
      compared with control horses administered saline. Palmar digital arterial blood
      flow in acepromazine-treated horses was not significantly different from that in
      control horses but increased significantly post-administration, compared with the
      respective baseline values for acepromazine-treated horses. PCV significantly
      decreased in horses administered acepromazine compared with their respective
      baseline value. CONCLUSION: IM acepromazine causes hypotension and increases
      palmar digital blood flow over time but the magnitude of the effect on digital
      blood flow was not sufficient to yield differences compared with saline-treated
      horses. CLINICAL RELEVANCE: IM acepromazine has a modest effect on palmar digital
      blood flow, facial arterial pressures and PCV in healthy horses with minimal
      sedation.

PMID- 18067612
TI  - Failure mode and bending moment of canine pancarpal arthrodesis constructs
      stabilized with two different implant systems.
AB  - OBJECTIVE: To compare failure mode and bending moment of a canine pancarpal
      arthrodesis construct using either a 2.7 mm/3.5 mm hybrid dynamic compression
      plate (HDCP) or a 3.5 mm dynamic compression plate (DCP). STUDY DESIGN: Paired in
      vitro biomechanical testing of canine pancarpal arthrodesis constructs stabilized
      with either a 2.7/3.5 HDCP or 3.5 DCP. SAMPLE POPULATION: Paired cadaveric canine
      antebrachii (n=5). METHODS: Pancarpal arthrodesis constructs were loaded to
      failure (point of maximum load) in 4-point bending using a materials-testing
      machine. Using this point of failure, bending moments were calculated from system
      variables for each construct and the 2 plating systems compared using a paired t
      test. To examine the relationship between metacarpal diameter and screw diameter
      failure loads, linear regression was used and Pearson' correlation coefficient
      was calculated. Significance was set at P<.05. RESULTS: HDCP failed at higher
      loads than DCP for 9 of 10 constructs. The absolute difference in failure rates
      between the 2 plates was 0.552+/-0.182 N m, P=.0144 (95% confidence interval: 
      0.58 to 1.68). This is an 8.1% mean difference in bending strength. There was a
      significant linear correlation r=0.74 (P-slope=.014) and 0.8 (P-slope=.006)
      between metacarpal diameter and failure loads for the HDCP and 3.5 DCP,
      respectively. CONCLUSION: There was a small but significant difference between
      bending moment at failure between 2.7/3.5 HDCP and 3.5 DCP constructs; however,
      the difference may not be clinically evident in all patients. CLINICAL RELEVANCE:
      The 2.7/3.5 HDCP has physical and mechanical properties making it a more
      desirable plate for pancarpal arthrodesis.

PMID- 18067613
TI  - In vitro biomechanical comparison of cervical disk arthroplasty, ventral slot
      procedure, and smooth pins with polymethylmethacrylate fixation at treated and
      adjacent canine cervical motion units.
AB  - OBJECTIVE: To compare the biomechanical properties of cervical arthroplasty to a
      ventral slot procedure and pin-polymethylmethacrylate (pin-PMMA) fixation. SAMPLE
      POPULATION: Fresh cadaveric cervical (C2-T1) spines from 6 large dogs. METHODS:
      Four spinal conditions were studied in each spinal specimen: intact, disk
      arthroplasty, ventral slot, and fixation with smooth pin-PMMA at C5-C6
      intervertebral space. Axial compression, torsion, flexion-extension, and lateral
      bending moments were sequentially tested on each specimen for the 4 spinal
      conditions. Data from the C3-C4, C4-C5, C5-C6, and C6-C7 vertebral motion units
      (VMUs) were compared among treatments. RESULTS: In axial compression and torsion,
      the ventral slot procedure allowed significantly less motion than intact, pin
      PMMA, and arthroplasty groups at C5-C6. In lateral bending and flexion-extension,
      pin-PMMA had the least motion of C5-C6, followed by the arthroplasty group,
      intact spine, and ventral slot, all of which were significantly different from
      each other. Overall, the artificial disk was better able to mimic the behavior of
      the intact specimens compared with the ventral slot and pin-PMMA, producing
      similar displacements in axial compression and rotation in torsion, but more
      limited motion than intact in flexion-extension and in lateral bending.
      CONCLUSION: Cervical spine specimens with an implanted prosthesis have
      biomechanical behaviors more similar to an intact spine compared with spinal
      specimens with ventral slot and pin-PMMA procedures. Cervical arthroplasty may
      then preserve some of the motion in the affected area after neural decompression
      while providing distraction. CLINICAL RELEVANCE: Cervical arthroplasty should be
      further investigated in vivo to determine if it is a viable alternative to the
      ventral slot or pin-PMMA procedures for surgical treatment of cervical diseases
      in dogs and in particular for treatment of disk-associated caudal cervical
      spondylomyelopathy.

PMID- 18067614
TI  - Biomechanical flexion-extension forces in normal canine lumbosacral cadaver
      specimens before and after dorsal laminectomy-discectomy and pedicle screw-rod
      fixation.
AB  - OBJECTIVE: To determine biomechanical flexion-extension forces in cadaveric
      canine lumbosacral specimens, before and after dorsal laminectomy with partial
      discectomy, and after dorsal pedicle screw-rod fixation of L7 and S1. STUDY
      DESIGN: Biomechanical cadaver study. ANIMALS: Cadaveric spine specimens without
      lumbosacral pathology from mature, intact Labrador retrievers (n=12). METHODS:
      Lumbosacral spine segments were subjected to a constant bending moment from L6 to
      S1 in a hydraulic 4-point bending materials testing machine. Force and
      displacement were recorded during each loading cycle constituting 1 complete
      flexion-extension cycle of the spine. Each spine segment had 3 series of
      recordings of 5 loading cycles each: (1) intact spine, (2) after surgical
      destabilization by dorsal laminectomy and partial discectomy, and (3) after
      surgical stabilization using dorsal pedicle screw-rod fixation. RESULTS: After
      dorsal laminectomy and partial discectomy, the neutral zone and range of motion
      were not different from those in the native spine specimen. After pedicle screw
      rod fixation, the neutral zone and range of motion of the instrumented specimen
      significantly (P<.0001) decreased compared with the native specimen and the
      specimen after dorsal laminectomy. CONCLUSION: Dorsal laminectomy and partial
      discectomy does not lead to significant spinal instability in flexion and
      extension whereas pedicle screw and rod fixation effectively stabilizes the
      lumbosacral spine. CLINICAL RELEVANCE: Dorsal laminectomy and partial discectomy
      does not lead to significant spinal instability. Pedicle screw-rod fixation of L7
      and S1 may be used to stabilize an unstable L7-S1 junction in dogs with
      degenerative lumbosacral stenosis.

PMID- 18067615
TI  - Immediate mandibular reconstruction of a 5 cm defect using rhBMP-2 after partial
      mandibulectomy in a dog.
AB  - OBJECTIVE: To report treatment of a complex odontoma of the mandible by partial
      mandibulectomy and immediate surgical reconstruction using bridging plate
      fixation with a synthetic graft. STUDY DESIGN: Clinical case report. ANIMALS: A 4
      year-old male castrated cocker spaniel. METHODS: Immediate reconstruction of the
      left mandible (5 cm gap) was performed after complete excision of a complex
      odontoma. Locking plate fixation was applied immediately before complete excision
      of the mass. Fixation was removed, then after partial mandibulectomy, including
      all abnormal tissue, restored to achieve occlusion. The resulting mandibular
      defect was filled with recombinant human bone morphogenetic protein-2 (rhBMP-2)
      delivered in an absorbable collagen sponge containing hydroxyapatite/tricalcium
      phosphate granules (compression resistant matrix [CRM]). RESULTS: New bone growth
      was evident radiographically and on palpation at 3 months. Bony remodeling was
      evident during follow-up examinations up to 26 months. Bone collected by biopsy
      at the graft site at 7 months had robust new bone formation and evidence of
      continued remodeling. Only minor complications (repeated intraoral plate
      exposure) were encountered postoperatively and were easily resolved. CONCLUSIONS:
      An osteoinductive factor (rhBMP-2/CRM) was successfully used as a graft
      substitute in immediate reconstruction of a large mandibular defect. CLINICAL
      RELEVANCE: Immediate reconstruction of large mandibular defects with
      osteoinductive materials as a graft substitute may be a viable alternative to
      partial mandibular resection or radiation therapy for benign odontogenic tumors
      in dogs.

PMID- 18067616
TI  - In vitro evaluation of a single injection technique for diagnostic analgesia of
      the proximal suspensory ligament of the equine pelvic limb.
AB  - OBJECTIVE: To examine the anatomic relationship of the deep branch of the lateral
      plantar nerve (DBLPN) with structures of the proximal metatarsal region, and to
      define the anatomic location of a solution injected using a single injection
      technique for diagnostic analgesia of the proximal suspensory ligament (PSL).
      STUDY DESIGN: Descriptive study. ANIMALS: Cadaveric equine pelvic limbs (n=29).
      METHODS: The proximal metatarsal region of both pelvic limbs (n=5 horses, 10
      limbs) was dissected and measurements were made of anatomic structures relative
      to the head of the 4th metatarsal bone (HMT4). A single injection technique was
      used to inject dye 15 mm distal to the HMT4, axial to the MT4 at a depth of 25 mm
      in each limb from 10 equine cadavers (19 limbs). Hindlimbs were dissected and the
      position of the dye was recorded. RESULTS: DBLPN branched from the lateral
      plantar nerve (LPN) at a mean distance of 30 mm proximal to the HMT4 and entered
      the PSL at a mean distance of 17 mm distal to the HMT4. A 2nd DBLPN was observed
      in 1 of 10 dissected limbs. Blue dye surrounded the DBLPN in 18 limbs (95%).
      CONCLUSIONS: A single injection technique was likely to have resulted in
      desensitization of the DBLPN in 18 of 19 limbs (95%). CLINICAL RELEVANCE: This
      technique provides a reliable method using a single needle puncture for
      perineural analgesia of the DBLPN for diagnosis of proximal suspensory desmitis
      of the pelvic limb with a minimal risk of inadvertently desensitizing structures
      within the tarsal sheath and the tarsometatarsal joint.

PMID- 18067617
TI  - A modified ventral approach to the atlantoaxial junction in the dog.
AB  - OBJECTIVE: To describe and evaluate a surgical technique using a modified ventral
      approach for stabilization of the atlantoaxial (AA) junction in dogs with AA
      subluxation. STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n=5) with AA
      subluxation. METHODS: Medical records (2000-2006) of 5 dogs with AA treated by
      stabilization via a right parasagittal approach were reviewed and outcome
      assessed by clinical examination and phone interviews with owners. RESULTS: The
      AA joint was clearly visualized and fixation devices were placed in all dogs. A
      right parasagittal approach provided excellent access to the AA junction and
      avoided dissection around the thyroid gland, trachea, and recurrent laryngeal
      nerve. Recovery was considered good to excellent by owners, and dogs returned to
      good function. CONCLUSIONS: A right parasagittal approach to the AA junction
      provides improved exposure and allows for surgical stabilization with minimal
      complications. CLINICAL RELEVANCE: In dogs that require surgical stabilization of
      the AA joint, a right parasagittal approach should be considered. This approach
      offers advantages over the standard ventral median approach by improved surgical
      exposure, less dissection, and provides protection of vital structures during
      insertion of fixation devices used for ventral AA stabilization.

PMID- 18067618
TI  - Fertility and complications after fetotomy in 20 brood mares (2001-2006).
AB  - OBJECTIVE: To report fertility (foals conceived, live foal births) of mares after
      partial fetotomy to resolve dystocia and complications associated with fetotomy.
      STUDY DESIGN: Retrospective study. ANIMALS: Horses (n=20). METHODS: Medical
      records (2001-2006) of mares that had partial fetotomy (1-3 cuts) for dystocia
      were reviewed. Complications and subsequent fertility were obtained by interview
      and live foal data were recorded by the Jockey Club. Postfetotomy conception and
      live foals produced over 21 breeding seasons (defined as years each mare was bred
      regardless of conception) were recorded. RESULTS: Twenty mares were identified.
      Bilateral carpal flexion alone (3 mares) or in combination with another deformity
      (7 mares) was the most common presentation for dystocia. From 2001 to 2006, there
      were 24 breeding seasons for which 20 mares conceived (83%). Eighteen mares
      conceived before 2006 and all produced live foals. Three mares were bred in 2006;
      2 became pregnant, 1 was electively aborted, and 1 is pregnant. Eight of 19 (42%)
      mares had retained placenta, which were expelled within 24 hours after medical
      therapy. CONCLUSION: Partial fetotomy performed with 1-3 cuts does not impede a
      successful reproductive future. CLINICAL RELEVANCE: In selected equine dystocia
      cases, partial fetotomy should be given primary consideration when the foal is
      dead and vaginal delivery cannot be readily achieved. Fetotomy should not
      adversely affect the future fertility of the mare.

PMID- 18067619
TI  - Use of a four pin and methylmethacrylate fixation in L7 and the iliac body to
      stabilize lumbosacral fracture-luxations: a clinical and anatomic study.
AB  - OBJECTIVES: To describe the clinical outcome of a 4 pin lumbosacral fixation
      technique for lumbosacral fracture-luxations, and to refine placement technique
      for iliac pins based on canine cadaver studies. STUDY DESIGN: Retrospective and
      anatomic study. SAMPLE POPULATION: Dogs (n=5) with lumbosacral fracture-luxations
      and 8 cadaveric canine pelvi. METHODS: Lumbosacral fracture-luxations were
      stabilized with a 4 pin (positive-profile threaded) and bone cement fixation.
      Caudal pins were inserted in the iliac body and cranial pins were inserted into
      the L7 or L6 pedicle and body. Follow-up examinations and radiographs were
      performed to assess patient outcome. Intramedullary pins were inserted into the
      iliac bodies of 8 cadaver pelvi. Radiographs were taken to measure pin insertion
      angles and define ideal insertion angles that would maximize pin purchase in the
      ilium. RESULTS: Follow-up neurologic examination was normal in 4 dogs.
      Radiographic healing of the fracture was evident in 5 dogs. One implant failure
      occurred but did not require re-operation. For cadaver iliac pins, mean
      craniocaudal insertion angle was 29 degrees and mean lateromedial insertion angle
      was 20 degrees. CONCLUSIONS: Four pin and bone cement fixation effectively
      stabilizes lumbosacral fracture luxations. The iliac body provides ample bone
      stock, which can be maximized using an average craniocaudal pin trajectory of 29
      degrees and an average lateromedial pin trajectory of 20 degrees. CLINICAL
      RELEVANCE: Lumbosacral fracture-luxations can be stabilized with 4 pin and bone
      cement fixation in the lumbar vertebrae and iliac body, using 29 and 20 degrees
      as guidelines for the craniocaudal and lateromedial pin insertion angles in the
      ilium.

PMID- 18067620
TI  - Estimated plasma bupivacaine concentration after single dose and eight-hour
      continuous intra-articular infusion of bupivacaine in normal dogs.
AB  - OBJECTIVE: To estimate maximum plasma concentration (C(max)) and time to maximum
      plasma (t(max)) bupivacaine concentration after intra-articular administration of
      bupivacaine for single injection (SI) and injection followed by continuous
      infusion (CI) in normal dogs. STUDY DESIGN: Cross-over design with a 2-week
      washout period. ANIMALS: Healthy Coon Hound dogs (n=8). METHODS: Using gas
      chromatography/mass spectrometry, canine plasma bupivacaine concentration was
      measured before and after SI (1.5 mg/kg) and CI (1.5 mg/kg and 0.3 mg/kg/h).
      Software was used to establish plasma concentration-time curves and estimate
      C(max), T(max) and other pharmacokinetic variables for comparison of SI and CI.
      RESULTS: Bupivacaine plasma concentration after SI and CI best fit a 3
      exponential model. For SI, mean maximum concentration (C(max), 1.33+/-0.954
      microg/mL) occurred at 11.37+/-4.546 minutes. For CI, mean C(max) (1.13+/-0.509
      microg/mL) occurred at 10.37+/-4.109 minutes. The area under the concentration
      time curve was smaller for SI (143.59+/-118.390 microg/mL x min) than for CI
      (626.502+/-423.653 microg/mL x min, P=.02) and half-life was shorter for SI
      (61.33+/-77.706 minutes) than for CI (245.363+/-104.415 minutes, P=.01). The
      highest plasma bupivacaine concentration for any dog was 3.2 microg/mL for SI and
      2.3 microg/mL for CI. CONCLUSION: Intra-articular bupivacaine administration
      results in delayed absorption from the stifle into the systemic circulation with
      mean C(max) below that considered toxic and no systemic drug accumulation.
      CLINICAL RELEVANCE: Intra-articular bupivacaine can be administered with small
      risk of reaching toxic plasma concentrations in dogs, though toxic concentrations
      may be approached. Caution should be exercised with multimodal bupivacaine
      administration because plasma drug concentration may rise higher than with single
      intra-articular injection.

PMID- 18067622
TI  - Endoscope-guided, transoral axial division of an entrapping epiglottic fold in
      fifteen standing horses.
AB  - OBJECTIVES: To describe and evaluate the use of a transoral, endoscope-guided
      technique for transection of an entrapping epiglottic fold in sedated standing
      horses. STUDY DESIGN: Retrospective study. ANIMALS: Horses (n=16) with epiglottic
      fold entrapment (EFE). METHODS: Medical records (2005-2006) of 16 horses with EFE
      were reviewed to determine history, physical and endoscopic examination findings,
      postoperative complications, and outcome after axial division of EFE using a
      hooked bistoury, under an endoscopic-guided, transoral approach. RESULTS: EFE was
      confirmed by endoscopy. Axial division was successfully performed in 15 sedated,
      standing horses. One horse had to be anesthetized to complete the procedure. None
      of the horses made abnormal respiratory noise after surgery and all returned to
      their intended use. After surgery, 1 horse had a short, deformed epiglottis.
      CONCLUSIONS: EFE can be axially divided safely and effectively using an endoscope
      guided, transoral approach, with the horse sedated and standing. CLINICAL
      RELEVANCE: Endoscopic-guided, transoral axial division of EFE in sedated standing
      horses is an alternative choice to performing this procedure under general
      anesthesia.

PMID- 18067621
TI  - In vitro biomechanical comparison of equine proximal interphalangeal joint
      arthrodesis techniques: prototype equine spoon plate versus axially positioned
      dynamic compression plate and two abaxial transarticular cortical screws inserted
      in lag fashion.
AB  - OBJECTIVES: To compare in vitro monotonic biomechanical properties of an equine
      spoon plate (ESP) with an axial 3-hole, 4.5 mm narrow dynamic compression plate
      (DCP) using 5.5 mm cortical screws in conjunction with 2 abaxial transarticular
      5.5 mm cortical screws (DCP-TLS) inserted in lag fashion for equine proximal
      interphalangeal (PIP) joint arthrodesis. STUDY DESIGN: Paired in vitro
      biomechanical testing of 2 methods of stabilizing cadaveric adult equine forelimb
      PIP joints. ANIMAL POPULATION: Cadaveric adult equine forelimbs (n=18 pairs).
      METHODS: For each forelimb pair, 1 PIP joint was stabilized with an ESP (8 hole,
      4.5 mm) and 1 with an axial 3-hole narrow DCP (4.5 mm) using 5.5 mm cortical
      screws in conjunction with 2 abaxial transarticular 5.5 mm cortical screws
      inserted in lag fashion. Six matching pairs of constructs were tested in single
      cycle to failure under axial compression with load applied under displacement
      control at a constant rate of 5 cm/s. Six construct pairs were tested for cyclic
      fatigue under axial compression with cyclic load (0-7.5 kN) applied at 6 Hz;
      cycles to failure were recorded. Six construct pairs were tested in single cycle
      to failure under torsional loading applied at a constant displacement rate (0.17
      radians/s) until rotation of 0.87 radians occurred. Mean values for each fixation
      method were compared using a paired t-test within each group with statistical
      significance set at P<.05. RESULTS: Mean yield load, yield stiffness, and failure
      load for ESP fixation were significantly greater (for axial compression and
      torsion) than for DCP-TLS fixation. Mean (+/- SD) values for the ESP and DCP-TLS
      fixation techniques, respectively, in single cycle to failure under axial
      compression were: yield load 123.9 +/- 8.96 and 28.5 +/- 3.32 kN; stiffness,
      13.11 +/- 0.242 and 2.60 +/- 0.17 kN/cm; and failure load, 144.4 +/- 13.6 and
      31.4 +/- 3.8 kN. In single cycle to failure under torsion, mean (+/- SD) values
      for ESP and DCP-TLS, respectively, were: stiffness 2,022 +/- 26.2 and 107.9 +/-
      11.1 N m/rad; and failure load: 256.4 +/- 39.2 and 87.1 +/- 11.5 N m. Mean cycles
      to failure in axial compression of ESP fixation (622,529 +/- 65,468) was
      significantly greater than DCP-TLS (95,418 +/- 11,037). CONCLUSION: ESP was
      superior to an axial 3-hole narrow DCP with 2 abaxial transarticular screws
      inserted in lag fashion in resisting static overload forces and cyclic fatigue.
      CLINICAL RELEVANCE: In vitro results support further evaluation of ESP for PIP
      joint arthrodesis in horses. Its specific design may provide increased stability
      without need for external coaptation support.

PMID- 18067623
TI  - Immune response profiles in human skin.
AB  - In addition to the function as a physical barrier human skin has been shown to be
      an important immune organ displaying various defense mechanisms, which can be
      divided into three major functional compartments: (i) Epithelial defense, which
      is characterized by antimicrobial peptides and proteins (AP) and which can be
      induced in inflammatory lesions but also in the absence of inflammation. (ii)
      Innate-inflammatory immunity, which involves recognition of microbial compounds
      by particular receptors like Toll-like receptors (TLR) and subsequent activation
      of signalling pathways resulting in expression of pro-inflammatory cytokines and
      interferons, as well as genes of adaptive immunity. Interferon alpha (IFNalpha)
      produced by plasmacytoid dendritic cells (DC) may stimulate myeloid DC to produce
      IL-12 resulting in classical T-cell activation or to produce IL-23 activating IL
      17 producing T-cells (IL-23/IL-17 pathway). (iii) Adaptive immunity, which is
      based on antigen presenting cells, T-cells and B-cells and which is characterized
      by specificity and memory. In contrast to epithelial defense and innate
      inflammatory immunity, adaptive immune functions provide slowly reacting
      protection. Recent improvements of our knowledge of dysregulated immune pathways
      associated with inflammatory skin diseases represent an important basis of novel
      immunomodulatory treatment modalities.

PMID- 18067624
TI  - Imiquimod: mode of action.
AB  - OBJECTIVE: Since imiquimod, a nucleoside analogue of the imidazoquinoline family,
      has shown efficacy against many tumour entities, its mode of action has become a
      focus of scientific interest. RESULTS: The major biologic effects of imiquimod
      are mediated through agonistic activity towards toll-like receptors (TLR) 7 and
      8, and consecutively, activation of nuclear factor-kappa B (NF-kappaB). The
      result of this activity is the induction of pro-inflammatory cytokines,
      chemokines and other mediators leading to activation of antigen-presenting cells
      and other components of innate immunity and, eventually, the mounting of a
      profound T-helper (Th1)-weighted antitumoral cellular immune response. Several
      secondary effects on the molecular and cellular level may also be explained, at
      least in part, by the activation of NF-kappaB. Moreover, independent of TLR-7 and
      TLR-8, imiquimod appears to interfere with adenosine receptor signalling
      pathways, and the compound causes receptor-independent reduction of adenylyl
      cyclase activity. This novel mechanism may augment the pro-inflammatory activity
      of the compound through suppression of a negative regulatory feedback mechanism
      which normally limits inflammatory responses. Finally, imiquimod induces
      apoptosis of tumour cells at higher concentrations. The pro-apoptotic activity of
      imiquimod involves caspase activation and appears to depend on B cell
      lymphoma/leukemia protein (Bcl)-2 proteins. CONCLUSIONS: Overall, imiquimod acts
      on several levels, which appear to synergistically underlie the profound
      antitumoral activity of the compound.

PMID- 18067625
TI  - Imiquimod treatment of papilloma virus and DMBA /TPA-induced cutaneous skin
      cancer in Mastomys coucha: an unique animal model system useful for preclinical
      studies.
AB  - BACKGROUND: Immune response modifiers including imiquimod can be topically
      applied for the treatment of both genital warts and benign and malignant skin
      tumours (e.g. actinic keratosis). In an initial pilot study, we examined the
      response of spontaneously papillomavirus caused skin lesions (e.g. papillomas,
      keratoacanthomas) vs. chemically induced skin tumours of Mastomys coucha to
      imiquimod. METHODS: Fourteen spontaneously and 16 chemically [initiation with
      7,12-dimethylbenzanthracene (DMBA) followed by repeated 12-O-Tetradecanoylphorbol
      13-acetate (TPA) applications] induced skin tumours were treated two to three
      times per week with 5% imiquimod or placebo. RESULTS: Notably, significant higher
      regression or growth arrest rates of imiquimod treated animals were observed in
      chemically vs. spontaneously induced skin tumours [9/14 (64%) vs. 2/11 (18%), P <
      0.05]. Regression or growth arrest of both skin tumours from placebo treated
      animals were similar (1/2 vs. 1/3). Tumour growth of nonresponders was lowest in
      imiquimod treated animals compared to the placebo or untreated group.
      CONCLUSIONS: Imiquimod was able to reduce skin tumour growth particularly in
      chemically induced lesions of Mastomys coucha. The different clearance rates are
      most likely due to lower differentiation status of the DMBA/TPA-induced tumours,
      allowing a better uptake of imiquimod than spontaneously induced papillomas or
      keratoacanthomas, known to be highly keratinized.

PMID- 18067626
TI  - Pathology and pathobiology of actinic (solar) keratosis - an update.
AB  - Actinic keratosis is a UV light-induced lesion and develops mostly in fair
      skinned patients being susceptible to solar damage. The term actinic keratosis
      (AK) describes clinically ill-defined reddish to reddish-brown scaly lesions on
      erythematous base in areas damaged severely by sunlight. The term does not imply
      anything about the biology or histopathology. Actinic keratoses (AKs) have been
      recognized as precursor of cancer or of precancerous lesions in the past but
      today they are considered as an early in situ squamous cell carcinoma (1,2) and
      are categorized in several classifications with subdivisions into three grades
      depending on the amount of atypical keratinocytes in the epidermis.(3-6) The
      incidence of development of AK in caucasians increases with age, proximity to the
      equator and outdoor occupation. Australia has the highest skin cancer rate in the
      world. AKs are discovered in up to 40-50% of the Australian population older than
      40 years.(7) AKs are the most common malignant lesion of the skin.(8-12).

PMID- 18067627
TI  - Management of field change in actinic keratosis.
AB  - Field cancerization was first described in 1953 as histologically altered mucosa
      surrounding tumours removed from the upper gastro-intestinal tract. Over the
      years the definition has changed to include an area which is clinically occult
      but has multifocal preneoplastic changes, showing genetic mutations and which
      precedes the development of second primary tumours and local recurrences. Field
      cancerization has been described in the oropharynx, oesophagus, stomach, lung,
      colon, anus, cervix, bladder and skin. Various molecular techniques have been
      developed to look for genetic mutations and clonality in areas of field change.
      These studies have highlighted the need for early detection and treatment in
      order to prevent the development of tumours and local recurrences. In this
      article we examine the concept of field cancerization and treatments available to
      manage field change.

PMID- 18067629
TI  - Update on actinic keratosis in clinical trial experience with imiquimod.
AB  - Actinic keratoses (AK) is a sun induced cutaneous lesion, currently considered as
      a squamous cell carcinoma in situ that has the potential to progress to invasive
      SCC. To treat them, numerous, ablative and no ablative, therapeutic approaches
      exist. Among them, imiquimod, a toll like receptor agonist, recently approved to
      treat them in the US and Europe, has demonstrated to be effective and safe with
      an acceptable tolerability in the treatment of these lesions. In this article the
      results of several high quality RCT are analysed.

PMID- 18067630
TI  - A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs.
      cryosurgery in immunocompetent patients with actinic keratoses: a comparison of
      clinical and histological outcomes including 1-year follow-up.
AB  - BACKGROUND: Actinic keratoses (AK) frequently occur on sun-exposed skin and are
      considered as in situ squamous cell carcinoma. To date, no treatment algorithm
      exists for first or second line therapies due to the lack of comparative studies.
      OBJECTIVE: This study compared the initial and 12-month clinical clearance,
      histological clearance, and cosmetic outcomes of topically applied 5% imiquimod
      (IMIQ) cream, 5% 5-fluorouracil (5-FU) ointment and cryosurgery for the treatment
      of AK. PATIENTS/METHODS: Patients were randomised to one of the following three
      treatment groups: one or two courses of cryosurgery (20-40 s per lesion), topical
      5-FU (twice daily for 4 weeks), or one or two courses of topical imquimod (three
      times per week for 4 weeks each). RESULTS: Sixty-eight per cent (17/25) of
      patients treated with cryosurgery, 96% (23/24) of patients treated with 5-FU, and
      85% (22/26) of patients treated with IMIQ achieved initial clinical clearance, p
      = 0.03. The histological clearance rate for cryosurgery was 32% (8/25), 67%
      (16/24) for 5-FU, and 73% (19/26) in the IMIQ group, p = 0.03. The 12-month
      follow-up showed a high rate of recurrent and new lesions in the 5-FU and
      cryosurgery arms. The sustained clearance rate of initially cleared individual
      lesions was 28% (7/25) for cryosurgery, 54% (13/24) for 5-FU and 73% (19/26) for
      IMIQ (p < 0.01). Sustained clearance of the total treatment field was 4% (1/25),
      33% (8/24), and 73% (19/26) of patients after cryosurgery, 5-FU, and IMIQ,
      respectively (p < 0.01). The patients in the IMIQ group were judged to have the
      best cosmetic outcomes (p = 0.0001). CONCLUSION: Imiquimod treatment of AK
      resulted in superior sustained clearance and cosmetic outcomes compared with
      cryosurgery and 5-FU. It should be considered as a first line therapy for
      sustained treatment of AK.

PMID- 18067628
TI  - Topical immunomodulation under systemic immunosuppression: results of a
      multicentre, randomized, placebo-controlled safety and efficacy study of
      imiquimod 5% cream for the treatment of actinic keratoses in kidney, heart, and
      liver transplant patients.
AB  - OBJECTIVE: In this study the safety and efficacy of imiquimod 5% cream for the
      treatments of actinic keratoses in kidney, heart and liver transplant recipients
      is evaluated. BACKGROUND: Growing populations of organ transplant recipients face
      increased risk of developing actinic keratosis (AK) and skin cancer secondary to
      continuous systemic immunosuppressive therapy. Imiquimod 5% cream is an effective
      option for the treatment of AK, but the safety of topical immune stimulation in
      immunocompromised patients has not been widely evaluated. METHODS: A total of 43
      patients in six European transplant centres applied two sachets of topical
      imiquimod or vehicle cream three times per week to a 100 cm(2) field. Dosing
      continued for 16 weeks regardless of lesion clearance. Patients were assessed for
      safety variables that included adverse events, local skin reactions, laboratory
      results, vital signs, dosage of immunosuppressive medication and indication of
      graft rejection. A blinded independent expert committee was responsible for
      safety monitoring and final safety assessment. RESULTS: No graft rejections or
      trends for a deterioration of graft function were detected. No meaningful trends
      were observed in laboratory results. Among patients randomized to imiquimod, the
      complete clearance rate was 62.1% (18/29); for vehicle patients, the complete
      clearance rate was 0% (0/14). Clinical clearance was confirmed histologically in
      all cases. CONCLUSIONS: Imiquimod appears to be a safe alternative for the
      treatment of multiple actinic keratoses in patients with solid organ transplants.
      Efficacy was within the range previously observed in nontransplanted populations.

PMID- 18067631
TI  - Multicentre, open-label study using imiquimod 5% cream in one or two 4-week
      courses of treatment for multiple actinic keratoses on the head.
AB  - OBJECTIVE: In the USA, Imiquimod 5% cream is approved for use 2-3 times per week
      over 16 weeks for the treatment of actinic keratoses (AKs). This study evaluated
      the efficacy of imiquimod in another treatment schedule, for AKs on the head.
      DESIGN: Open-label, phase IIIb. SETTING: 180 dermatology clinics and practices in
      Germany. PATIENTS: Patients were eligible if they had clinically typical, visible
      AK lesions located anywhere on the head, excluding the upper and lower eyelids,
      nostrils, lip vermilion, and inside the ears. INTERVENTIONS: Patients applied
      study cream to the treatment area once daily 3x/week for 4 weeks (course 1)
      followed by a 4-week post-treatment period. Patients with AK lesions remaining in
      the treatment area underwent a second 4-week treatment course. MAIN OUTCOME
      MEASURES: Primary variable was the complete clearance rate, defined as the
      proportion of patients with no clinically visible AK lesions in the treatment
      area at the course 1 or course 2 post-treatment visit. RESULTS: 829 patients
      entered the study. Overall, the complete clearance rate was 68.9% (571/829) and
      the partial clearance rate (percentage of patients with >/= 75% reduction in the
      number of baseline AK lesions) was 80.2%. Local skin reactions (LSRs) and
      application site reactions (ASRs) were the most commonly reported adverse events.
      Four patients discontinued from the study due to LSRs or ASRs. CONCLUSIONS:
      Shorter treatment regimen of imiquimod 5% cream can produce complete clearance
      rates similar to those seen with 16 weeks of treatment and has the advantage of
      lower drug exposure, resulting in a better benefit-risk profile for the patient.

PMID- 18067632
TI  - Epidemiology and aetiology of basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is a malignant epithelial neoplasm of the skin
      preferentially affecting male caucasians and is rarely observed in patients with
      more intense skin pigmentation. A characteristic feature of BCCs are their
      extremely low risk to metastasize. Epidemiological data indicate that the overall
      incidence is increasing worldwide significantly by about 3-10% per annum.(1-3)
      Based on the increasing incidence of this usually not life-threatening tumour BCC
      appears to develop into a growing public health problem. This review elucidates
      the risk factors for the development and for the progression of BCC leading to an
      improved understanding of this tumour.

PMID- 18067633
TI  - Evaluation of imiquimod for the therapy of external genital and anal warts in
      comparison with destructive therapies.
AB  - External genital and anal warts (acuminate condyloma) were the first medical
      indication the topical immune response modifier imiquimod was approved for in
      1997. Since then, many placebo controlled randomized clinical trials have
      demonstrated the efficacy and safety of this synthetic imidazoquinoline derivate
      for the treatment of different human papillomavirus infections and tumours.
      Treatment modalities for genital warts (5% cream, three times weekly, minimum
      duration 4 weeks, control of side-effects) have been optimized and assured by
      further clinical trials and meta-analyses. For a few years clinical studies
      focussed on the long-term efficacy of the immunomodulatory therapy (sustained
      clearance from warts) and most recent studies compared the efficacy of ablative,
      destructive and imiquimod monotherapy as well as combination therapies.

PMID- 18067634
TI  - Noninvasive diagnostic tools for nonmelanoma skin cancer.
AB  - Minimally invasive diagnostic tools have received increased attention for
      diagnosis, screening and management of nonmelanoma skin cancer (NMSC). Several
      modalities are commercially available, including high frequency ultrasound,
      optical coherence tomography and confocal microscopy. While systematic clinical
      analyses are often lacking, recent reports have shown promising results for
      reflectance confocal microscopy (RCM) for diagnosis of actinic keratoses and
      basal cell carcinoma.

PMID- 18067635
TI  - Significance of chemoprevention for prostate cancer development: experimental in
      vivo approaches to chemoprevention.
AB  - Prostate cancer is the most common tumor in men in Western countries and
      mortality in Asian countries from the disease appears to be constantly
      increasing. Characteristics include (i) frequent discovery of latent carcinoma,
      even in countries with low incidences of clinical cancer; (ii) very long time to
      clinically significant cancer; (iii) few patients under 50 years of age
      (primarily a disease of elderly men); (iv) strong influences of environmental
      factors such as food; (v) temporal effectiveness of androgen deprival therapy;
      and (vi) no effective therapeutic approaches once hormone-refractory neoplasms
      have developed. Therefore prostate cancer is particularly indicated for
      preventive efforts, especially chemoprevention. Several large-scale
      chemoprevention trials have in fact been conducted and some have found
      suppressive effects. However, not all have been proven to have benefit.
      Experimental preclinical investigations, particularly using animal models, are
      recommended to find better chemopreventive agents with less adverse effects. Data
      using rat models have generated very interesting findings from which mechanism
      based strategies can be proposed. In the present report the importance of
      chemoprevention of prostate cancer will be discussed using the data on human and
      rat prostate cancer development.

PMID- 18067636
TI  - Expression and amplification of Her2, EGFR and cyclin D1 in breast cancer:
      immunohistochemistry and chromogenic in situ hybridization.
AB  - Determination of Her2, epidermal growth factor receptor (EGFR) and cyclin D1
      status is now of major clinical importance due to the development of molecule
      targeting drugs in anticancer therapy. Immunohistochemistry (IHC) and chromogenic
      in situ hybridization (CISH) are the most simple and convenient methods for
      evaluating gene alterations and their protein consequences. The purpose of the
      present study was to investigate the status of Her2, EGFR and cyclin D1 on both
      IHC and CISH in 95 primary breast carcinomas. There was substantial consistency
      between the IHC and CISH results of Her2 and EGFR, showing fair agreement between
      protein overexpression and gene amplification. However, cyclin D amplification
      was not related to protein overexpression. Moreover, there was no correlation
      between Her2, EGFR and cyclin D1. Her2 protein overexpression and amplification
      were positively associated with histological grade, nuclear grade and inversely
      correlated with the expression of estrogen receptor (ER) and progesterone
      receptor (PR). In ER-negative and postmenopausal patients, EGFR gene
      amplification was strongly associated with worse recurrence-free survival (P =
      0.0087, P = 0.0149, respectively). Overall, the present findings suggest that
      EGFR gene amplification is important in predicting prognosis and this should be
      evaluated in breast carcinoma in addition to Her2 status in routine pathological
      practice.

PMID- 18067637
TI  - Clinicopathological study of invasive ductal carcinoma with large central
      acellular zone: special reference to magnetic resonance imaging findings.
AB  - Invasive ductal carcinoma (IDC) with central acellular zone is sometimes
      encountered, but its clinicopathological features have not yet been fully
      investigated. The clinicopathological features of 10 resected cases of IDC with a
      large central acellular zone were investigated. The tumor size ranged from 6 to
      28 mm with a mean of 14.3 +/- 6.9 mm. Contrast-enhanced magnetic resonance
      imaging (MRI) showed a ring-like appearance in the tumor. Sagittal fat-suppressed
      T2-weighted MRI had very high to intermediate signal intensity in a central area.
      Histologically, cancer tissue was located in the periphery of the tumor with a
      ring-like pattern and a large central area was occupied by acellular amorphous
      tissue that was strongly stained by alcian blue. Lymph vessel permeation was seen
      in eight cases. Among the tumors with focal enhancement in the central areas >1
      cm in diameter on contrast MRI, marked increase of microvessel was observed in
      the enhanced spot. The mean of p53 and Ki-67 labeling indices was 56.2% and
      36.3%, respectively. IDC with a large central acellular zone presenting with
      characteristic MRI should be noted as a new morphological entity.

PMID- 18067638
TI  - Immunohistochemical expression of TTF-1 in various cytological subtypes of
      primary lung adenocarcinoma, with special reference to intratumoral
      heterogeneity.
AB  - The immunohistochemical expression of thyroid transcription factor-1 (TTF-1) was
      investigated in various cytological subtypes of primary lung adenocarcinoma, with
      special reference to intratumoral heterogeneity. Three groups were categorized
      according to cytological subtype: group A, adenocarcinomas with either a Clara
      cell and/or type II epithelial cell component (Clara/type II) or a mixed
      Clara/type II and bronchial surface epithelial cell component (BSE) (mCB), in
      addition to other components; group B, adenocarcinomas with components including
      either BSE, a goblet cell component (GOB) or a mixed BSE and GOB component (mBG),
      and lacking Clara/type II or mCB; group C, adenocarcinomas with only a poorly
      differentiated component (POR). In group A all Clara/type II, mCB, BSE and the
      majority of POR were TTF-1 positive. In group B the majority of BSE, POR and all
      GOB were TTF-1 negative. BSE and POR in both groups had a different phenotype,
      possibly reflecting their different natural history. In group C 80% of cases were
      TTF-1 positive, suggesting that the majority were derived from group A tumors.

PMID- 18067639
TI  - Role of the PI3K/Akt, mTOR, and STK11/LKB1 pathways in the tumorigenesis of
      sclerosing hemangioma of the lung.
AB  - Although the histogenesis of sclerosing hemangioma (SH) of the lung is now
      thought to be respiratory epithelial in origin, the genetic abnormalities that
      mediate its development are not known. Because pathophysiology of several
      syndromes associated with benign tumors may converge on the tuberous sclerosis
      complex (TSC), serine/threonine kinase 11 (STK11), and mammalian target of
      rapamycin (mTOR) pathways, the purpose of the present paper was to investigate
      their roles in the development of SH. Semiquantitative immunohistochemical
      analysis was done to assess the expression of phospho-mTOR, phospho-S6 ribosomal
      protein, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phospho
      Akt, STK11, tuberin, hamartin, vascular endothelial growth factor (VEGF), and
      hypoxia-inducible factor-1alpha (HIF-1alpha) in 19 cases of typical SH. To
      determine whether genetic alteration of STK11 is involved in the development of
      SH, all encoding exons of STK11 were analyzed by polymerase chain reaction (PCR)
      amplification and direct sequencing of genomic DNA of six specimens. The six
      specimens were also investigated for whether promoter hypermethylation exists as
      an alternative inactivating mechanism for STK11. All specimens showed moderate to
      marked reaction to phospho-S6 ribosomal protein and PTEN; 16 specimens (84%)
      showed slight to moderate reaction to phospho-mTOR, negative reaction to STK11,
      and slight to moderate reaction to hamartin; 11 (58%) showed slight to moderate
      reaction to phospho-Akt; 18 (95%) showed slight to moderate reaction to tuberin
      and positive reaction for HIF-1alpha; and 17 (90%) showed moderate reaction to
      VEGF. No somatic mutation of STK11 was found and the six specimens were
      unmethylated in the promoter region. These data imply that aberrant mTOR
      signaling may play a role in the development of SH, and its vascular nature may
      be due partially to high levels of VEGF caused by dysregulation of mTOR
      signaling.

PMID- 18067640
TI  - Prognostic significance of gastric cancer metastasis in second-tier lymph nodes
      detected on reverse transcriptase-polymerase chain reaction and
      immunohistochemistry.
AB  - To determine the prognostic significance of the methods used to determine the
      presence of metastasis in second-tier lymph nodes of patients with gastric
      cancer, the authors studied lymph nodes surgically removed from 100 patients with
      gastric cancer (55 with early cancer, 45 with progressive). The results of HE
      staining were compared with those of immunohistochemistry using the
      anticytokeratin (CK) antibody and reverse transcriptase-polymerase chain reaction
      (RT-PCR) assays. Lymph node 7 or 8a was obtained intraoperatively, then mRNA was
      extracted using an immunobeads method, and RT-PCR with CK19 mRNA was performed.
      The P for Cox regression analysis for metastasis detected by HE staining, CK
      staining, and RT-PCR of all 100 cases was 0.312, 0.426, and 0.021, respectively,
      while for second-tier lymph nodes it was 0.154, 0.013, and 0.006, respectively.
      In conclusion, RT-PCR and CK staining for detection of metastasis in second-tier
      lymph nodes were more reliable prognostic indicators than conventional HE
      staining.

PMID- 18067641
TI  - Carcinoid tumor of the renal pelvis: consideration on the histogenesis.
AB  - Carcinoid tumor of the renal pelvis is an extremely rare neoplasm and only two
      cases have been previously reported in the English-language literature. Reported
      herein is a third case of carcinoid tumor arising in the renal pelvis. The tumor
      extending from the left renal pelvis into the left kidney was incidentally found
      in a 55-year-old Japanese woman. Macroscopically, the tumor was predominantly
      located in the dilated renal pelvis and was grayish-white on cut surface.
      Microscopically, neoplastic cells proliferated with a ribbon-like, trabecular,
      tubular and solid pattern. Furthermore, the tumor focally invaded the kidney
      parenchyma. No precursor lesion of neuroendocrine tumor was observed in the
      peripheral urothelial epithelium. Neither urothelial carcinoma nor teratoma
      component was observed within the tumorous mass. The cytoplasm of neoplastic
      cells was focally positive for Grimelius stain and focally positive for
      chromogranin A and synaptophysin. However, no neoplastic cells reacted with
      cytokeratins 7 and 20. Ultrastructurally, neoplastic cells contained dense core
      granules in the cytoplasm. Urologists and pathologists should recognize that
      carcinoid tumor may arise from the renal pelvis.

PMID- 18067642
TI  - Histopathology of the thyroid in amiodarone-induced hypothyroidism.
AB  - Amiodarone is well recognized as an anti-arrhythmic drug containing a high dose
      of iodine with considerable potential to cause thyroid dysfunction. The present
      patient was a 66-year-old Japanese woman who developed a cardiac arrhythmia and
      was given amiodarone as an anti-arrhythmic agent for approximately 3 months,
      until the day before her death. However, 19 days after starting amiodarone, serum
      testing indicated a hypothyroid status that was not recognized clinically. At
      autopsy, microscopy showed that most of the thyroid follicles were enlarged with
      dense colloid substance and lined by flattened follicular cells (involuted
      follicles). There were a small number of damaged follicles infiltrated by
      macrophages, which were immunopositive for HAM56. Sudan IV staining indicated
      many lipid droplets in follicular cells. Ultrastructurally the follicular cells
      contained large residual bodies composed of abundant electron-lucent lipid
      droplets of variable size. Although it is difficult to be certain of the direct
      link of amiodarone on the basis of a single case, it is reasonable to presume
      that this histopathology is associated with amiodarone-induced hypothyroidism and
      that involution changes represent the hypofunctional status of this drug-induced
      disorder. This is the first report on the histopathological findings of thyroid
      tissue from a patient with amiodarone-induced hypothyroidism.

PMID- 18067643
TI  - Focal hepatic steatosis surrounding a metastatic insulinoma.
AB  - Reported herein is a case of focal hepatic steatosis surrounding a metastatic
      insulinoma in the liver of a 69-year-old woman. The patient complained of losing
      consciousness after meals, and hypoglycemia and hyperinsulinemia were confirmed.
      On CT and abdominal angiography a mass, 1 cm in diameter, was seen in the tail of
      the pancreas. In the early phase of dynamic CT a mass, 5 mm in diameter, was seen
      in the liver. In the late phase this mass appeared to be 3 cm in diameter. An
      arterial calcium stimulation/venous sampling test showed insulin levels after
      calcium injections in the hepatic artery to be extremely high. Thus, the liver
      tumor was diagnosed as a metastatic insulinoma, and distal pancreatectomy and
      partial resection of the liver were performed. The pancreatic tumor cells were
      immunohistochemically positive for insulin. The liver tumor was pale yellow. A
      white area surrounded the tumor. Histologically, the liver tumor was an
      insulinoma and the white area was focal fatty change of the liver. High insulin
      levels are said to inhibit oxidation of free fatty acids into triglycerides,
      causing free fatty acids to accumulate in hepatocytes. Focal hepatic steatosis
      caused by the local effects of insulin can present as a focal rim surrounding a
      metastatic insulinoma.

PMID- 18067645
TI  - Lymphoepithelioma-like cholangiocarcinoma not associated with EBV.
AB  - Reported herein is an unusual case of intrahepatic cholangiocarcinoma with
      lymphoepithelioma-like appearance in a 64-year-old man who was found to have an
      intrahepatic mass without cirrhosis. The tumor had two distinct histological
      patterns with dense lymphoplasmacytic infiltrate. The first was similar to
      nasopharyngeal undifferentiated carcinoma; the second pattern was a well
      differentiated adenocarcinoma. Transition between the two components was observed
      in the same duct. Immunohistochemistry indicated that the tumor was
      immunoreactive with AE1/AE3 and cytokeratin (CK) 7, but negative for CEA and
      CK20. Stromal inflammatory infiltrate primarily consisted of plasma cells and
      lymphocytes. Immunohistochemical examination and in situ hybridization for EBV
      showed no integration of the virus in the tumor cells. Intrahepatic
      lymphoepithelioma-like carcinoma is rare, and most are associated with EBV. Only
      three cases were not associated with EBV. The authors would like to add one more
      example of the tumors not associated with EBV.

PMID- 18067644
TI  - Osteopontin expression in the liver with severe perisinusoidal fibrosis: autopsy
      case of Down syndrome with transient myeloproliferative disorder.
AB  - Down syndrome with transient myeloproliferative disorder (TMD) is often
      associated with perinatal liver fibrosis. The authors recently encountered an
      autopsy case of this disease with a characteristic severe perisinusoidal liver
      fibrosis. Osteopontin (OPN) is a molecule that plays an important role in diverse
      fibro-inflammatory diseases. The purpose of the present report was to examine the
      involvement of OPN in development of the Down syndrome-associated liver fibrosis.
      Histology indicated severe perisinusoidal fibrosis and ductular arrangements of
      hepatocytes in the liver. Appearance of atypical megakaryocytes in the liver, a
      feature of TMD associated with Down syndrome, was not evident. On
      immunohistochemistry expression of OPN was observed in hepatocytes often having
      ductular arrangements and infiltrating macrophages. In contrast, a small number
      of transforming growth factor-beta1 (TGF-beta1)-positive mononuclear cells were
      present in the liver. Numerous activated hepatic stellate cells (HSC) expressing
      alpha-smooth muscle actin (alpha-SMA) were seen in the perisinusoidal area. A
      recent report indicated that OPN could directly activate the HSC. Thus, it is
      suggested that OPN produced by hepatocytes and macrophages induces activation of
      the HSC, and leads to the development of perisinusoidal liver fibrosis.

PMID- 18067646
TI  - Transfusion-transmitted infections among multitransfused patients in Iran: a
      review.
AB  - Transfusion-transmitted infections (TTI) continue to be a major challenge for
      Blood transfusion organizations across the world. The problem is more serious in
      the developing countries with lower economic means. Multitransfused patients
      (MTPs) in these countries are at higher risk of infection, and studies of
      infection in these patients can be a useful index for examining the blood safety
      filters in place. The present article reviews the situation in Iran, where
      prevalence of the major viruses of concern, namely, hepatitis B virus, hepatitis
      C virus (HCV) and human immunodeficiency virus, studied in these patients is
      reported over a 9-year period. It is demonstrated that HCV is the most prevalent
      TTI and remains a major health problem for these patients.

PMID- 18067647
TI  - Reducing replacement donors in Sub-Saharan Africa: challenges and affordability.
AB  - In 1975, the World Health Assembly recommended that blood for transfusion should
      come from voluntary, non-remunerated donors; yet, in Africa, 75-80% of blood for
      transfusion still comes from hospital-based replacement donors. Although
      comprehensive economic data are scarce, evidence indicates that blood from
      voluntary donors recruited and screened at centralized transfusion centres, costs
      four to eight times as much as blood from a hospital-based, replacement donor
      system. Donor recruitment, quality assurance systems and distribution mechanisms
      in the centralized system are major reasons for the cost difference. There are
      concerns about the sustainability of centralized voluntary donor systems and
      their compatibility with the levels of health care that exist in many poor
      countries yet burdening patients' families with the responsibility of finding
      replacement blood donors will exacerbate poverty and reduce the safety of the
      blood supply. There are measures that can be introduced into hospital-based
      systems to improve safe blood supply in Africa but their effectiveness in
      different contexts needs to be evaluated.

PMID- 18067648
TI  - Factors that motivate and hinder blood donation in Greece.
AB  - Donations in Greece are insufficient to cover the high transfusion needs arising
      from large numbers of thalassaemia and sickle cell anaemia patients and the
      implementation of new surgical techniques. Efforts to achieve self-sufficiency,
      and to render blood supplies safer and manageable must focus on recruiting and
      retaining more volunteer donors and on converting the large pool of replacement
      donors. The aim of the study was to gain insight into public perception regarding
      the risks of donation and transfusion and to identify the factors that would
      motivate more people in Greece to regularly donate blood. Questionnaires were
      distributed to 1,600 donors at the blood bank and visitors to hospitals at 11
      locations across the country. Data on demographics, donation behaviour,
      incentives, risk perception and attitudes towards donation and transfusion were
      analysed separately for volunteer and replacement donors and non-donors. The
      results showed that women and young people donate the least in Greece. Also, many
      donors do not donate because they are not reminded to. A small percentage of
      donors confessed to having concealed part of the truth to background questions.
      Overall, incentives to donate were considered important and included future
      availability of blood for self or family, paid leave from work and free blood
      tests. Recruitment and retention efforts should include better communication with
      current donors, and raising awareness among eligible donors. Staff should be
      educated in soliciting information from potential donors, and incentives should
      be better aligned to avoid conflict with ethical values and ensure honesty in the
      prescreening process.

PMID- 18067649
TI  - Why don't women volunteer to give blood? A study of knowledge, attitude and
      practice of women about blood donation, Yazd, Iran, 2005.
AB  - The most important aim of all blood transfusion centres is to recruit blood
      donors from low-risk groups of society to donate blood voluntarily and regularly.
      In the city of Yazd, Iran, only 5% of blood donors are women. The aim of this
      study was to assess barriers of donation of blood by women and the level of
      knowledge, attitude and practice regarding blood donation. In this cross
      sectional study, 1602 women were selected by cluster sampling method and asked to
      fill a specially formatted questionnaire. Data were analysed by ANOVA and the t
      test. Levels of knowledge were different between the various groups. Illiterate
      women and housewives had the least levels of knowledge. Fifteen per cent of the
      women had donated blood at least once in the past. The most important
      motivational factor was sense of moral duty with a spiritual reward and the most
      important barriers for donating blood were anaemia, fear, lack of time and
      difficulty in access to donation sites. A significant percentage of women had
      false beliefs about blood donation. Increase in the level of knowledge of women
      and correction of false beliefs should be the topmost priority. Further studies
      are needed to determine whether addressing anaemia and women's health can tend to
      increase the number of female blood donors.

PMID- 18067650
TI  - Comparison of acute non-haemolytic transfusion reactions in female and male
      patients receiving female or male blood components.
AB  - To study the relationship between antibodies detected in patients' and/or donors'
      sera and the clinical features of acute non-haemolytic transfusion reactions
      (ANHTRs), and to determine any gender-related difference. ANHTRs range from
      urticaria to transfusion-related acute lung injury (TRALI). Antibodies to human
      leukocyte antigen (HLA), granulocytes, platelets, and/or plasma proteins are
      implicated in some of the ANHTRs. A higher antibody positivity is expected for
      females than for males. A comparative study of ANHTRs for antibody positivity and
      their clinical features between females and males for both patients and donors is
      helpful for characterizing ANHTRs including TRALI more clearly, but such studies
      are few and outdated. Two hundred and twenty-three ANHTR cases reported by 45
      hospitals between October 2000 and July 2005 were analysed. The patients and 196
      donors of suspect blood products were screened for antibodies to HLA Class I, HLA
      Class II, granulocytes, and platelets. The patients were also screened for anti
      plasma protein antibodies. The types and severity of ANHTR did not differ
      significantly between female and male patients. The frequency of the anti-HLA
      antibodies, but not that of the non-HLA antibodies, was significantly higher in
      females. Non-HLA antibodies were significantly associated with severe reactions
      in females. All the TRALI cases had predisposing risk factors for acute lung
      injury, and 60% of the cases showed anti-leucocyte antibodies. Although the anti
      HLA antibodies were detected more frequently in females than males, no
      significant association of ANHTRs including TRALI with gender, not only for
      patients, but also for donors, could be shown in this study.

PMID- 18067651
TI  - Assessment of corrected QT interval in sickle-cell disease patients who undergo
      erythroapheresis.
AB  - Extension of the QT interval is characterized by syncope and cardiac arrest and
      often occurs in association with medical therapies and procedures. Whether
      erythroapheresis (EPH) could influence the QT interval duration in patients with
      sickle cell disease (SCD) is not known. We aimed to investigate the effects of
      EPH on the heart rate-corrected QT (QTc) interval. The study included 25 patients
      with SCD who underwent 34 EPH procedures. Two independent observers measured QTc
      interval duration from electrocardiograms performed continuously for 3 min at
      three different points during the EPH procedures (prior to EPH, after completion
      of 50% EPH and 15 min after EPH). Multiple regression analysis was used to
      determine if the ionized plasma calcium, the level of plasma magnesium, citrate
      infusion rate and painful crisis significantly contributed to the QTc interval.
      There was a non-significant trend (P = 0.184) towards increased QTc in sickle
      cell patients during EPH compared with pre-EPH values. QTc prolongation (>440 ms)
      occurred in 72% of the procedures. Fifty percent QTc values returned to baseline
      after the procedure. The independent variables were not significantly associated
      with QTc interval. Exchange procedures can induce QTc prolongation in patients
      with SCD.

PMID- 18067652
TI  - Gene frequencies of the HPA-1 platelet antigen alleles in the Lebanese
      population.
AB  - The objective was to study the gene frequencies of HPA-1 in the Lebanese
      population for the first time. The aims of this study were to assess the
      prevalence of 1a and 1b HPA-1 alleles in healthy Lebanese individuals and compare
      with the international literature. Human platelet antigen (HPA) systems are
      involved in alloimmunization, organ transplantation rejection and the development
      of cardiovascular disease. Of several classified HPA systems, HPA-1 specifically
      has been considered to be the most important antigenic system implicated in the
      Caucasian population. This specific gene has never been investigated in our
      population. DNA was extracted from specimens collected from 205 healthy unrelated
      Lebanese individuals and tested, using a reverse hybridization polymerase chain
      reaction (PCR) assay, for the prevalence of 1a and 1b HPA-1 alleles. Genotypes
      1a/1a, 1a/1b, and 1b/1b were assigned accordingly. We observed that the 1a/1a
      genotype was the most prevalent (65.85%) followed by 1a/1b (30.24%) and 1b/1b
      (3.91%) with allelic frequencies for 1a and 1b of 0.81 and 0.19, respectively. As
      compared with other ethnic groups, the Lebanese population was found to have a
      relatively high prevalence of the HPA-1b, which may predispose to a higher risk
      of alloimmunization. This report is the first to study the prevalence of the HPA
      1 system in the Lebanese population and serves as a template for future clinical
      research involving platelet disorders and cardiovascular diseases.

PMID- 18067653
TI  - Preliminary data for genotype distribution and epidemiological aspects of
      hepatitis C virus infection in blood donors from Yucatan, Mexico.

PMID- 18067655
TI  - Contribution of telomerase RNA retrotranscription to DNA double-strand break
      repair during mammalian genome evolution.
AB  - BACKGROUND: In vertebrates, tandem arrays of TTAGGG hexamers are present at both
      telomeres and intrachromosomal sites (interstitial telomeric sequences (ITSs)).
      We previously showed that, in primates, ITSs were inserted during the repair of
      DNA double-strand breaks and proposed that they could arise from either the
      capture of telomeric fragments or the action of telomerase. RESULTS: An extensive
      comparative analysis of two primate (Homo sapiens and Pan troglodytes) and two
      rodent (Mus musculus and Rattus norvegicus) genomes allowed us to describe
      organization and insertion mechanisms of all the informative ITSs present in the
      four species. Two novel observations support the hypothesis of telomerase
      involvement in ITS insertion: in a highly significant fraction of informative
      loci, the ITSs were introduced at break sites where a few nucleotides homologous
      to the telomeric hexamer were exposed; in the rodent genomes, complex ITS loci
      are present in which a retrotranscribed fragment of the telomerase RNA, far away
      from the canonical template, was inserted together with the telomeric repeats.
      Moreover, mutational analysis of the TTAGGG arrays in the different species
      suggests that they were inserted as exact telomeric hexamers, further supporting
      the participation of telomerase in ITS formation. CONCLUSION: These results
      strongly suggest that telomerase was utilized, in some instances, for the repair
      of DNA double-strand breaks occurring in the genomes of rodents and primates
      during evolution. The presence, in the rodent genomes, of sequences
      retrotranscribed from the telomerase RNA strengthens the hypothesis of the origin
      of telomerase from an ancient retrotransposon.

PMID- 18067656
TI  - Gene-expression patterns reveal underlying biological processes in Kawasaki
      disease.
AB  - BACKGROUND: Kawasaki disease (KD) is an acute self-limited vasculitis and the
      leading cause of acquired heart disease in children in developed countries. No
      etiologic agent(s) has been identified, and the processes that mediate formation
      of coronary artery aneurysms and abatement of fever following treatment with
      intravenous immunoglobulin (IVIG) remain poorly understood. RESULTS: In an
      initial survey, we used DNA microarrays to examine patterns of gene expression in
      peripheral whole blood from 20 children with KD; each was sampled during the
      acute, subacute, and convalescent phases of the illness. Acute KD was
      characterized by increased relative abundance of gene transcripts associated with
      innate immune and proinflammatory responses and decreased abundance of
      transcripts associated with natural killer cells and CD8+ lymphocytes. There was
      significant temporal variation in transcript levels during the acute disease
      phase and stabilization thereafter. We confirmed these temporal patterns in a
      second cohort of 64 patients, and identified additional inter-individual
      differences in transcript abundance. Notably, higher levels of transcripts of the
      gene for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) were
      associated with an increased percentage of unsegmented neutrophils, fewer days of
      illness, higher levels of C-reactive protein, and subsequent non-response to
      IVIG; this last association was confirmed by quantitative reverse transcription
      PCR in a third cohort of 33 patients, and was independent of day of illness.
      CONCLUSION: Acute KD is characterized by dynamic and variable gene-expression
      programs that highlight the importance of neutrophil activation state and
      apoptosis in KD pathogenesis. Our findings also support the feasibility of
      extracting biomarkers associated with clinical prognosis from gene-expression
      profiles of individuals with systemic inflammatory illnesses.

PMID- 18067657
TI  - Single-drug therapy or selective decontamination of the digestive tract as
      antifungal prophylaxis in critically ill patients: a systematic review.
AB  - INTRODUCTION: The objective of this study was to determine and compare the
      effectiveness of different prophylactic antifungal therapies in critically ill
      patients on the incidence of yeast colonisation, infection, candidemia, and
      hospital mortality. METHODS: A systematic review was conducted of prospective
      trials including adult non-neutropenic patients, comparing single-drug antifungal
      prophylaxis (SAP) or selective decontamination of the digestive tract (SDD) with
      controls and with each other. RESULTS: Thirty-three studies were included (11 SAP
      and 22 SDD; 5,529 patients). Compared with control groups, both SAP and SDD
      reduced the incidence of yeast colonisation (SAP: odds ratio [OR] 0.38, 95%
      confidence interval [CI] 0.20 to 0.70; SDD: OR 0.12, 95% CI 0.05 to 0.29) and
      infection (SAP: OR 0.54, 95% CI 0.39 to 0.75; SDD: OR 0.29, 95% CI 0.18 to 0.45).
      Treatment effects were significantly larger in SDD trials than in SAP trials. The
      incidence of candidemia was reduced by SAP (OR 0.32, 95% CI 0.12 to 0.82) but not
      by SDD (OR 0.59, 95% CI 0.25 to 1.40). In-hospital mortality was reduced
      predominantly by SDD (OR 0.73, 95% CI 0.59 to 0.93, numbers needed to treat 15;
      SAP: OR 0.80, 95% CI 0.64 to 1.00). Effectiveness of prophylaxis reduced with an
      increased proportion of included surgical patients. CONCLUSION: Antifungal
      prophylaxis (SAP or SDD) is effective in reducing yeast colonisation and
      infections across a range of critically ill patients. Indirect comparisons
      suggest that SDD is more effective in reducing yeast-related outcomes, except for
      candidemia.

PMID- 18067658
TI  - The effects of hip muscle strengthening on knee load, pain, and function in
      people with knee osteoarthritis: a protocol for a randomised, single-blind
      controlled trial.
AB  - BACKGROUND: Lower limb strengthening exercises are an important component of the
      treatment for knee osteoarthritis (OA). Strengthening the hip abductor and
      adductor muscles may influence joint loading and/or OA-related symptoms, but no
      study has evaluated these hypotheses directly. The aim of this randomised, single
      blind controlled trial is to determine whether hip abductor and adductor muscle
      strengthening can reduce knee load and improve pain and physical function in
      people with medial compartment knee OA. METHODS/DESIGN: 88 participants with
      painful, radiographically confirmed medial compartment knee OA and varus
      alignment will be recruited from the community and randomly allocated to a hip
      strengthening or control group using concealed allocation stratified by disease
      severity. The hip strengthening group will perform 6 exercises to strengthen the
      hip abductor and adductor muscles at home 5 times per week for 12 weeks. They
      will consult with a physiotherapist on 7 occasions to be taught the exercises and
      progress exercise resistance. The control group will be requested to continue
      with their usual care. Blinded follow up assessment will be conducted at 12 weeks
      after randomisation. The primary outcome measure is the change in the peak
      external knee adduction moment measured during walking. Questionnaires will
      assess changes in pain and physical function as well as overall perceived rating
      of change. An intention-to-treat analysis will be performed using linear
      regression modelling and adjusting for baseline outcome values and other
      demographic characteristics. DISCUSSION: Results from this trial will contribute
      to the evidence regarding the effect of hip strengthening on knee loads and
      symptoms in people with medial compartment knee OA. If shown to reduce the knee
      adduction moment, hip strengthening has the potential to slow disease
      progression. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry
      ACTR12607000001493.

PMID- 18067659
TI  - Clinical effectiveness of usual care with or without antidepressant medication
      for primary care patients with minor or mild-major depression: a randomized
      equivalence trial.
AB  - BACKGROUND: Minor and mild-major depression are highly prevalent in primary care.
      There is insufficient evidence for the effectiveness of antidepressants in the
      treatment of minor and mild-major depression. We compared the effectiveness of
      usual primary care treatment, with or without antidepressants, in minor and mild
      major depression. METHODS: A pragmatic patient-randomized equivalence trial with
      52 weeks follow-up was conducted in The Netherlands. In total, 59 primary care
      physicians (PCPs) recruited and treated 181 adult patients with minor or mild
      major depression. Patients were randomized to four consultations within 3 months
      of usual care plus antidepressants (UCandAD) or usual care alone (UCnoAD). The
      Montgomery Asberg Depression Rating Scale (MADRS) was used to assess changes in
      severity of depressive symptoms. The predefined equivalence margin was set at
      five points. Multilevel analysis was used to analyze the data. Secondary outcome
      measures were the Short-Form 36 (SF-36), and the Client Satisfaction
      Questionnaire (CSQ-8). RESULTS: Patients received on average 3.0 (SD 1.4) 15-min
      consultations within 3 months with (n = 85) or without paroxetine (n = 96).
      Equivalence of UCandAD and UCnoAD was demonstrated in the intention-to-treat
      analyses as well as the per-protocol analysis after 6 weeks, but not at 13, 26
      and 52 weeks follow-up. No statistical differences in effectiveness between
      treatment groups were found in the intention-to-treat analysis. No differences in
      the physical and mental functioning (SF-36) were found between the treatment
      groups. Patients allocated to UCandAD were slightly more satisfied with their
      treatment at 13 weeks follow-up (but not at 52 weeks follow-up) than patients
      allocated to UCnoAD. Preliminary analyses suggested that subgroups such as
      patients with mild-major (instead of a minor) depression might benefit from
      antidepressant treatment. Patients who were assigned to their preferred treatment
      (in particular to UCnoAD) were more often compliant and had better clinical
      outcomes. CONCLUSION: UCandAD was as effective as UCnoAD over the first 6 weeks,
      but not at 13, 26, and 52 weeks. However, superiority of either treatment could
      not be demonstrated either. The question whether antidepressants add any clinical
      effect to usual care remains unresolved. We recommend future studies to look for
      subgroups of patients who may benefit from antidepressants. TRIAL REGISTRATION:
      Dutch Trial Registry ISRCN03007807.

PMID- 18067660
TI  - Ethics of open access to biomedical research: just a special case of ethics of
      open access to research.
AB  - The ethical case for Open Access (OA) (free online access) to research findings
      is especially salient when it is public health that is being compromised by
      needless access restrictions. But the ethical imperative for OA is far more
      general: It applies to all scientific and scholarly research findings published
      in peer-reviewed journals. And peer-to-peer access is far more important than
      direct public access. Most research is funded so as to be conducted and
      published, by researchers, in order to be taken up, used, and built upon in
      further research and applications, again by researchers (pure and applied,
      including practitioners), for the benefit of the public that funded it - not in
      order to generate revenue for the peer-reviewed journal publishing industry (nor
      even because there is a burning public desire to read much of it). Hence OA needs
      to be mandated, by researchers' institutions and funders, for all research.

PMID- 18067661
TI  - Vitamin D receptor polymorphisms and breast cancer risk in a large population
      based case-control study of Caucasian and African-American women.
AB  - INTRODUCTION: The involvement of vitamin D receptor (VDR), which is a key
      mediator in the vitamin D pathway, in breast cancer etiology has long been of
      interest. METHODS: We examined the association between polymorphisms in the 3'
      end of the VDR gene, specifically BsmI and Poly(A), and breast cancer risk within
      a large, population-based, case-control study of breast cancer. Cases (n = 1,631)
      were Caucasian and African-American women, aged 35 to 64 years, who were
      diagnosed with incident, invasive breast cancer between July 1994 and April 1998.
      Control individuals (n = 1,435) were women without breast cancer ascertained
      through random digit dialing. RESULTS: Accounting for age, study site, and
      sampling weights, we observed a significantly increased risk for breast cancer
      among Caucasian, postmenopausal carriers of the bb genotype of BsmI (odds ratio =
      1.53, 95% confidence interval = 1.04 to 2.27). However, no associations with the
      bb genotype were observed in African-American women. Overall, there were no
      significant associations between the Poly(A) genotype and breast cancer risk in
      either racial group. Smoking status (ever/never) modified the association between
      both the BsmI and Poly(A) genotypes and breast cancer risk. The respective
      associations between these genotypes and breast cancer risk did not significantly
      vary by oral contraceptive use, hormone replacement therapy, or body mass index.
      CONCLUSION: Our results provide additional support for an increased risk for
      breast cancer in postmenopausal Caucasian women with the BsmI bb genotype and
      shed light on possible differential effects by menopausal status and race.

PMID- 18067663
TI  - The JSpecView Project: an Open Source Java viewer and converter for JCAMP-DX, and
      XML spectral data files.
AB  - The JSpecView Open Source project began with the intention of providing both a
      teaching and research tool for the display of JCAMP-DX spectra. The development
      of the Java source code commenced under license in 2001 and was released as Open
      Source in March 2006. The scope was then broadened to take advantage of the XML
      initiative in Chemistry and routines to read and write AnIML and CMLspect
      documents were added.JSpecView has the ability to display the full range of JCAMP
      DX formats and protocols and to display multiple spectra simultaneously. As an
      aid for the interpretation of spectra it was found useful to offer routines such
      that if any part of the spectral display is clicked, that region can be
      highlighted and the (x, y) coordinates returned. This is conveniently handled
      using calls from JavaScript and the feedback results can be used to initiate
      links to other applets like Jmol, to generate a peak table, or even to load audio
      clips providing helpful hints.Whilst the current user base is still small, there
      are a number of sites that already feature the applet. A tutorial video showing
      how to examine NMR spectra using JSpecView has appeared on YouTube and was
      formatted for replay on iPods and it has been incorporated into a chemistry
      search engine.

PMID- 18067662
TI  - Single-cell duplex RT-LATE-PCR reveals Oct4 and Xist RNA gradients in 8-cell
      embryos.
AB  - BACKGROUND: The formation of two distinctive cell lineages in preimplantation
      mouse embryos is characterized by differential gene expression. The cells of the
      inner cell mass are pluripotent and express high levels of Oct4 mRNA, which is
      down-regulated in the surrounding trophectoderm. In contrast, the trophectoderm
      of female embryos contains Xist mRNA, which is absent from cells of the inner
      mass. Prior to blastocyst formation, all blastomeres of female embryos still
      express both of these RNAs. We, thus, postulated that simultaneous quantification
      of Oct4 and Xist transcripts in individual blastomeres at the 8-cell stage could
      be informative as to their subsequent fate. Testing this hypothesis, however,
      presented numerous technical challenges. We overcame these difficulties by
      combining PurAmp, a single-tube method for RNA preparation and quantification,
      with LATE-PCR, an advanced form of asymmetric PCR. RESULTS: We constructed a
      duplex RT-LATE-PCR assay for real-time measurement of Oct4 and Xist templates and
      confirmed its specificity and quantitative accuracy with different methods. We
      then undertook analysis of sets of blastomeres isolated from embryos at the 8
      cell stage. At this stage, all cells in the embryo are still pluripotent and
      morphologically equivalent. Our results demonstrate, however, that both Oct4 and
      Xist RNA levels vary in individual blastomeres comprising the same embryo, with
      some cells having particularly elevated levels of either transcript. Analysis of
      multiple embryos also shows that Xist and Oct4 expression levels are not
      correlated at the 8-cell stage, although transcription of both genes is up
      regulated at this time in development. In addition, comparison of data from males
      and females allowed us to determine that the efficiency of the Oct4/Xist assay is
      unaffected by sex-related differences in gene expression. CONCLUSION: This paper
      describes the first example of multiplex RT-LATE-PCR and its utility, when
      combined with PurAmp sample preparation, for quantitative analysis of transcript
      levels in single cells. With this technique, copy numbers of different RNAs can
      be accurately measured independently from their relative abundance in a cell, a
      goal that cannot be achieved using symmetric PCR. The technique illustrated in
      this work is relevant to a wide array of applications, such as stem cell and
      cancer cell analysis and preimplantation genetic diagnostics.

PMID- 18067664
TI  - Pancytopenia due to iron deficiency worsened by iron infusion: a case report.
AB  - INTRODUCTION: Iron deficiency anemia is commonly associated with thrombocytosis,
      although thrombocytopenia has been reported in occasional patients with iron
      deficiency anemia. Much less common is the development of thrombocytopenia
      following replenishment of iron stores. CASE PRESENTATION: We present the unusual
      case of a 39 year old African American female Jehovah's Witness who presented
      with a 10 month history of menorrhagia and pancytopenia. Laboratory
      investigations confirmed a severe iron deficiency. Since blood transfusion was
      unacceptable to her, she was started on intravenous iron replacement therapy.
      This precipitated a sudden drop in both her platelet and white blood cell counts.
      Histopathological examination of the bone marrow revealed a hypercellular marrow
      with orderly trilineage hematopoiesis, iron deficiency anemia, granulocytic
      hyperplasia, and mild megakaryocytic hypoplasia. Both her white blood cell and
      platelet counts recovered uneventfully with continuing iron supplementation. The
      possible mechanism for this phenomenon is discussed in this report. CONCLUSION:
      This case illustrates two rather uncommon associations of a very common problem.
      Severe iron deficiency anemia may be associated with pancytopenia and iron
      replacement may cause a transient decline in megakaryopoiesis and leukopoiesis.
      Severe iron deficiency should be added to the list of conditions leading to
      thrombocytopenia.

PMID- 18067665
TI  - Microsatellite based genetic diversity and relationships among ten Creole and
      commercial cattle breeds raised in Brazil.
AB  - BACKGROUND: Brazil holds the largest commercial cattle populations worldwide.
      Local cattle breeds can be classified according to their origin, as exotic or
      Creole. Exotic breeds imported in the last 100 years, both zebuine and taurine,
      currently make up the bulk of the intensively managed populations. Locally
      adapted Creole breeds, originated from cattle introduced by the European
      conquerors derive from natural selection and events of breed admixture. While
      historical knowledge exists on the Brazilian Creole breeds very little is known
      on their genetic composition. The objective of this study was to assess the
      levels of genetic diversity, phylogenetic relationships and patterns of
      taurine/zebuine admixture among ten cattle breeds raised in Brazil. RESULTS:
      Significant reduction of heterozygosity exists due both to within-population
      inbreeding and to breed differentiation in both subspecies (taurine and zebuine).
      For taurine breeds the number of markers that contribute to breed differentiation
      is larger than for zebuine. A consistently similar number of alleles was seen in
      both subspecies for all microsatellites. Four Creole breeds were the most
      genetically diverse followed by the zebuine breeds, the two specialized taurine
      breeds and the Creole Caracu. Pairwise genetic differentiation were all
      significant indicating that all breeds can be considered as genetically
      independent entities. A STRUCTURE based diagram indicated introgression of
      indicine genes in the local Creole breeds and suggested that occasional Creole
      introgression can be detected in some Zebuine animals. CONCLUSION: This study
      reports on a comprehensive study of the genetic structure and diversity of cattle
      breeds in Brazil. A significant amount of genetic variation is maintained in the
      local cattle populations. The genetic data show that Brazilian Creole breeds
      constitute an important and diverse reservoir of genetic diversity for bovine
      breeding and conservation. The genetic data was able to shed light on a number of
      issues related to the local breeds origin and structure. The Brazilian Creole
      breeds are all important and viable targets for conservation for they display
      peculiar traits both phenotypic and of cultural and historical nature that
      deserve conservation efforts.

PMID- 18067666
TI  - Length of pressure-controlled reperfusion is critical for reducing ischaemia
      reperfusion injury in an isolated rabbit lung model.
AB  - BACKGROUND: Ischaemia-reperfusion injury is still a major problem after lung
      transplantation. Several reports describe the benefits of controlled graft
      reperfusion. In this study the role of length of the initial pressure-controlled
      reperfusion (PCR) was evaluated in a model of isolated, buffer-perfused rabbit
      lungs. METHODS: Heart-lung blocks of 25 New Zealand white rabbits were used.
      After measurement of baseline values (haemodynamics and gas exchange) the lungs
      were exposed to 120 minutes of hypoxic warm ischaemia followed by repeated
      measurements during reperfusion. Group A was immediately reperfused using a flow
      of 100 ml/min whereas groups B, C and D were initially reperfused with a maximum
      pressure of 5 mmHg for 5, 15 or 30 minutes, respectively. The control group had
      no period of ischaemia or PCR. RESULTS: Uncontrolled reperfusion (group A) caused
      a significant pulmonary injury with increased pulmonary artery pressures (PAP)
      and pulmonary vascular resistance and a decrease in oxygen partial pressure
      (PO2), tidal volume and in lung compliance. All groups with PCR had a
      significantly higher PO2 for 5 to 90 min after start of reperfusion. At 120 min
      there was also a significant difference between group B (264 +/- 91 mmHg)
      compared to groups C and D (436 +/- 87 mmHg; 562 +/- 20 mmHg, p < 0.01). All PCR
      groups showed a significant decrease of PAP compared to group A. CONCLUSION:
      Uncontrolled reperfusion results in a severe lung injury with rapid oedema
      formation. PCR preserves pulmonary haemodynamics and gas exchange after ischaemia
      and might allows for recovery of the impaired endothelial function. 30 minutes of
      PCR provide superior results compared to 5 or 15 minutes of PCR.

PMID- 18067667
TI  - Splenic peliosis - a potentially fatal condition which can mimick malignancy.
AB  - Isolated splenic peliosis is an extremely rare occurrence, and this disease
      often manifests itself with spontaneous haemoperitoneum.We report a case where an
      otherwise healthy patient was found to have splenomegaly on clinical examination.
      On computerised tomography, a diagnosis of splenic malignancy was made, and the
      patient underwent a splenectomy. Histological examination gave the diagnosis of
      splenic peliosis, which had not been considered prior to the operation. In
      retrospect, splenectomy was the most prudent course of action, as the risk of
      spontaneous haemorrhage and fatality was eliminated. This case emphasises the
      need to retain an index of suspicion for this condition, even in otherwise
      healthy patients, and is a reminder of the usefulness of total splenectomy in the
      current era of minimally invasive diagnostic techniques.

PMID- 18067668
TI  - Complicated Crohn's-like colitis, associated with Hermansky-Pudlak syndrome,
      treated with Infliximab: a case report and brief review of the literature.
AB  - INTRODUCTION: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive
      inherited disorder consisting of a triad of albinism, increased bleeding tendency
      secondary to platelet dysfunction, and systemic complications associated with
      ceroid depositions within the reticuloendothelial system. HPS has been associated
      with gastrointestinal (GI) complications related to chronic granulomatous colitis
      with pathologic features suggestive of Crohn's disease. This colitis can be
      severe and has been reported to be poorly responsive to medical therapies
      including antibiotics, corticosteroids, sulfasalazine, mesalamine and
      azathioprine. CASE PRESENTATION: We report a patient with HPS which was
      complicated by inflammatory bowel disease with clinical and pathologic features
      of Crohn's disease, refractory to antibiotics, corticosteroids and azathioprine.
      A trial of infliximab was attempted and repeated infusions produced a complete
      response. CONCLUSION: The occurrence of ileitis and perianal lesions and also the
      histopathological findings in our case suggest that HPS and Crohn's disease may
      truly be associated. Given this similarity and the failure of the standard
      medical therapy of corticosteroids and azathioprine, our patient received
      infliximab with marked clinical improvement.

PMID- 18067669
TI  - A systematic approach to detecting transcription factors in response to
      environmental stresses.
AB  - BACKGROUND: Eukaryotic cells have developed mechanisms to respond to external
      environmental or physiological changes (stresses). In order to increase the
      activities of stress-protection functions in response to an environmental change,
      the internal cell mechanisms need to induce certain specific gene expression
      patterns and pathways by changing the expression levels of specific transcription
      factors (TFs). The conventional methods to find these specific TFs and their
      interactivities are slow and laborious. In this study, a novel efficient method
      is proposed to detect the TFs and their interactivities that regulate yeast genes
      that respond to any specific environment change. RESULTS: For each gene expressed
      in a specific environmental condition, a dynamic regulatory model is constructed
      in which the coefficients of the model represent the transcriptional activities
      and interactivities of the corresponding TFs. The proposed method requires only
      microarray data and information of all TFs that bind to the gene but it has
      superior resolution than the current methods. Our method not only can find stress
      specific TFs but also can predict their regulatory strengths and interactivities.
      Moreover, TFs can be ranked, so that we can identify the major TFs to a stress.
      Similarly, it can rank the interactions between TFs and identify the major
      cooperative TF pairs. In addition, the cross-talks and interactivities among
      different stress-induced pathways are specified by the proposed scheme to gain
      much insight into protective mechanisms of yeast under different environmental
      stresses. CONCLUSION: In this study, we find significant stress-specific and cell
      cycle-controlled TFs via constructing a transcriptional dynamic model to regulate
      the expression profiles of genes under different environmental conditions through
      microarray data. We have applied this TF activity and interactivity detection
      method to many stress conditions, including hyper- and hypo- osmotic shock, heat
      shock, hydrogen peroxide and cell cycle, because the available expression time
      profiles for these conditions are long enough. Especially, we find significant
      TFs and cooperative TFs responding to environmental changes. Our method may also
      be applicable to other stresses if the gene expression profiles have been
      examined for a sufficiently long time.

PMID- 18067670
TI  - Community-based HIV prevention research among substance-using women in survival
      sex work: the Maka Project Partnership.
AB  - Substance-using women who exchange sex for money, drugs or shelter as a means of
      basic subsistence (ie. survival sex) have remained largely at the periphery of
      HIV and harm reduction policies and services across Canadian cities. This is
      notwithstanding global evidence of the multiple harms faced by this population,
      including high rates of violence and poverty, and enhanced vulnerabilities to HIV
      transmission among women who smoke or inject drugs. In response, a participatory
      action research project was developed in partnership with a local sex work agency
      to examine the HIV-related vulnerabilities, barriers to accessing care, and
      impact of current prevention and harm reduction strategies among women in
      survival sex work. This paper provides a brief background of the health and drug
      related harms among substance-using women in survival sex work, and outlines the
      development and methodology of a community-based HIV prevention research project
      partnership. In doing so, we discuss some of the strengths and challenges of
      community-based HIV prevention research, as well as some key ethical
      considerations, in the context of street-level sex work in an urban setting.

PMID- 18067671
TI  - Echocardiographic assessment of mitral valve morphology after Percutaneous
      Transvenous Mitral Commissurotomy (PTMC).
AB  - AIMS: PTMC produces significant changes in mitral valve morphology as improvement
      in leaflets mobility. The determinants of such improvement have not been assessed
      before. METHODS AND RESULTS: The study included 291 symptomatic patients with
      mitral stenosis undergoing PTMC. Post-PTMC subvalvular splitting area was a
      determinant of post-PTMC excursion in both the anterior (B 0.16, 95% CI 0.03 to
      0.30, p < 0.05) and the posterior (B 0.12, 95% CI 0.01 to 0.24, p < 0.05)
      leaflets. Another determinant was the post-PTMC transmitral pressure gradient for
      anterior (B -0.02, 95% CI -0.04 to -0.005, p < 0.01) and posterior (B -0.01, 95%
      CI -0.04 to -0.005, p < 0.05) leaflets excursion. The relationship between post
      PTMC MVA and leaflet excursion was non-linear "S curve". There was a steep
      increase of both anterior (p, 0.02) and posterior (p, 0.03) leaflets excursion
      with increased MVA till the MVA reached a value of about 1.5 cm2; after which
      both linear and S curves became nearly parallel. CONCLUSION: The improvement in
      leaflets excursion after PTMC is determined by several morphologic and
      hemodynamic changes produced in the valve. The increase in MVA improves mobility
      within limit; after which any further increase in MVA is not associated by a
      significant improvement in mobility in both leaflets.

PMID- 18067672
TI  - Differences in susceptibility to German cockroach frass and its associated
      proteases in induced allergic inflammation in mice.
AB  - BACKGROUND: Cockroach exposure is a major risk factor for the development of
      asthma. Inhalation of fecal remnants (frass) is the likely sensitizing agent;
      however isolated frass has not been tested for its ability to induce experimental
      asthma in mice. METHODS: Mice (Balb/c or C57Bl/6) were sensitized and challenged
      with GC frass or GC frass devoid of proteases and measurements of airway
      inflammation and hyperresponsiveness were performed (interleukin (IL)-5, -13, and
      interferon gamma (IFNgamma) levels in bronchoalveolar lavage fluid, serum IgE
      levels, airway hyperresponsiveness, cellular infiltration, and mucin production).
      RESULTS: Sensitization and challenge of Balb/c mice with GC frass resulted in
      increased airway inflammation and hyperresponsiveness. C57Bl/6 mice were not
      susceptible to this model of sensitization; however they were sensitized to GC
      frass using a more aggressive sensitization and challenge protocol. In mice that
      were sensitized by inhalation, the active serine proteases in GC frass played a
      role in airway hyperresponsiveness as these mice had less airway
      hyperresponsiveness to acetylcholine and less mucin production. Proteases did not
      play a role in mediating the allergic inflammation in mice sensitized via
      intraperitoneal injection. CONCLUSION: While both strains of mice were able to
      induce experimental asthma following GC frass sensitization and challenge, the
      active serine proteases in GC frass only play a role in airway
      hyperresponsiveness in Balb/c mice that were susceptible to sensitization via
      inhalation. The differences in the method of sensitization suggest genetic
      differences between strains of mice.

PMID- 18067673
TI  - Floret-like multinucleated giant cells in neurofibroma.
AB  - This short report discusses a case of neurofibroma containing floret-like
      multinucleated giant cells. This being the second such case in the literature.
      Floret-like multinucleated giant cells have been reported in gynaecomastia and
      neurofibroma in neurofibromatosis type 1. These cells have been reported in
      uncommon soft tissue tumours including pleomorphic lipoma, giant cell
      collagenoma, giant cell fibroblastoma and giant cell angiofibroma. We recommend
      these cells to be interpreted carefully keeping in mind the rare malignant change
      in neurofibromas. Immunohistochemistry would help in defining the nature of such
      cells.

PMID- 18067674
TI  - Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan
      syndrome.
AB  - Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is
      an inborn error of purine metabolism associated with uric acid overproduction and
      a continuum spectrum of neurological manifestations depending on the degree of
      the enzymatic deficiency. The prevalence is estimated at 1/380,000 live births in
      Canada, and 1/235,000 live births in Spain. Uric acid overproduction is present
      inall HPRT-deficient patients and is associated with lithiasis and gout.
      Neurological manifestations include severe action dystonia, choreoathetosis,
      ballismus, cognitive and attention deficit, and self-injurious behaviour. The
      most severe forms are known as Lesch-Nyhan syndrome (patients are normal at birth
      and diagnosis can be accomplished when psychomotor delay becomes apparent).
      Partial HPRT-deficient patients present these symptoms with a different
      intensity, and in the least severe forms symptoms may be unapparent.
      Megaloblastic anaemia is also associated with the disease. Inheritance of HPRT
      deficiency is X-linked recessive, thus males are generally affected and
      heterozygous female are carriers (usually asymptomatic). Human HPRT is encoded by
      a single structural gene on the long arm of the X chromosome at Xq26. To date,
      more than 300 disease-associated mutations in the HPRT1 gene have been
      identified. The diagnosis is based on clinical and biochemical findings
      (hyperuricemia and hyperuricosuria associated with psychomotor delay), and
      enzymatic (HPRT activity determination in haemolysate, intact erythrocytes or
      fibroblasts) and molecular tests. Molecular diagnosis allows faster and more
      accurate carrier and prenatal diagnosis. Prenatal diagnosis can be performed with
      amniotic cells obtained by amniocentesis at about 15-18 weeks' gestation, or
      chorionic villus cells obtained at about 10-12 weeks' gestation. Uric acid
      overproduction can be managed by allopurinol treatment. Doses must be carefully
      adjusted to avoid xanthine lithiasis. The lack of precise understanding of the
      neurological dysfunction has precluded development of useful therapies.
      Spasticity, when present, and dystonia can be managed with benzodiazepines and
      gamma-aminobutyric acid inhibitors such as baclofen. Physical rehabilitation,
      including management of dysarthria and dysphagia, special devices to enable hand
      control, appropriate walking aids, and a programme of posture management to
      prevent deformities are recommended. Self-injurious behaviour must be managed by
      a combination of physical restraints, behavioural and pharmaceutical treatments.

PMID- 18067675
TI  - Regulator of G-protein signalling 2 mRNA is differentially expressed in mammary
      epithelial subpopulations and over-expressed in the majority of breast cancers.
AB  - INTRODUCTION: To understand which signalling pathways become deregulated in
      breast cancer, it is necessary to identify functionally significant gene
      expression patterns in the stem, progenitor, transit amplifying and
      differentiated cells of the mammary epithelium. We have previously used the
      markers 33A10, CD24 and Sca-1 to identify mouse mammary epithelial cell
      subpopulations. We now investigate the relationship between cells expressing
      these markers and use gene expression microarray analysis to identify genes
      differentially expressed in the cell populations. METHODS: Freshly isolated
      primary mouse mammary epithelial cells were separated on the basis of staining
      with the 33A10 antibody and an alpha-Sca-1 antibody. The populations identified
      were profiled using gene expression microarray analysis. Gene expression patterns
      were confirmed on normal mouse and human mammary epithelial subpopulations and
      were examined in a panel of breast cancer samples and cell lines. RESULTS:
      Analysis of the separated populations demonstrated that Sca-1- 33A10High stained
      cells were estrogen receptor alpha (Esr1)- luminal epithelial cells, whereas Sca
      1+ 33A10Low/- stained cells were a mix of nonepithelial cells and Esr1+
      epithelial cells. Analysis of the gene expression data identified the gene Rgs2
      (regulator of G-protein signalling 2) as being highly expressed in the Sca-1-
      33A10Low/- population, which included myoepithelial/basal cells. RGS2 has
      previously been described as a regulator of angiotensin II receptor signalling.
      Gene expression analysis by quantitative real-time RT-PCR of cells separated on
      the basis of CD24 and Sca-1 expression confirmed that Rgs2 was more highly
      expressed in mouse myoepithelial/basal mammary cells than luminal cells. This
      expression pattern was conserved in normal human breast cells. Functional
      analysis demonstrated RGS2 to be a modulator of oxytocin receptor signalling. The
      potential significance of RGS2 expression in breast cancer was demonstrated by
      semi-quantitative RT-PCR analysis, data mining and quantitative real-time RT-PCR
      approaches, which showed that RGS2 was expressed in the majority of solid breast
      cancers at much higher levels than in normal human mammary cells. CONCLUSION:
      Molecular analysis of prospectively isolated mammary epithelial cells identified
      RGS2 as a modulator of oxytocin receptor signalling, which is highly expressed in
      the myoepithelial cells. The RGS2 gene, but not the oxytocin receptor, was also
      shown to be over-expressed in the majority of breast cancers, identifying the
      product of this gene, or the pathway(s) it regulates, as potentially significant
      therapeutic targets.

PMID- 18067676
TI  - Muscle fatigue in relation to forearm pain and tenderness among professional
      computer users.
AB  - BACKGROUND: To examine the hypothesis that forearm pain with palpation tenderness
      in computer users is associated with increased extensor muscle fatigue. METHODS:
      Eighteen persons with pain and moderate to severe palpation tenderness in the
      extensor muscle group of the right forearm and twenty gender and age matched
      referents without such complaints were enrolled from the Danish NUDATA study of
      neck and upper extremity disorders among technical assistants and machine
      technicians. Fatigue of the right forearm extensor muscles was assessed by muscle
      twitch forces in response to low frequency (2 Hz) percutaneous electrical
      stimulation. Twitch forces were measured before, immediately after and 15 minutes
      into recovery of an extensor isometric wrist extension for ten minutes at 15 %
      Maximal Voluntary Contraction (MVC). RESULTS: The average MVC wrist extension
      force and baseline stimulated twitch forces were equal in the case and the
      referent group. After the fatiguing contraction, a decrease in muscle average
      twitch force was seen in both groups, but the decrease was largest in the
      referent group: 27% (95% CI 17-37) versus 9% (95% CI -2 to 20). This difference
      in twitch force response was not explained by differences in the MVC or body mass
      index. CONCLUSION: Computer users with forearm pain and moderate to severe
      palpation tenderness had diminished forearm extensor muscle fatigue response.
      Additional studies are necessary to determine whether this result reflects an
      adaptive response to exposure without any pathophysiological significance, or
      represents a part of a causal pathway leading to pain.

PMID- 18067677
TI  - Effects of ingesting JavaFit Energy Extreme functional coffee on aerobic and
      anaerobic fitness markers in recreationally-active coffee consumers.
AB  - The purpose of this study was to examine the effects of ingesting JavaFittrade
      mark Energy Extreme (JEE) on aerobic and anaerobic performance measures in
      recreationally-active male and female coffee drinkers. Five male (27.6 +/- 4.2
      yrs, 93.2 +/- 11.7 kg, 181.6 +/- 6.9 cm) and five female (29 +/- 4.6 yrs, 61.5 +/
      9.2 kg, 167.6 +/- 6.9 cm) regular coffee drinkers (i.e., 223.9 +/- 62.7 mg.d-1
      of caffeine) participated in this study. In a cross-over, randomized design,
      participants performed a baseline (BASELINE) graded treadmill test (GXT) for peak
      VO2 assessment and a Wingate test for peak power. Approximately 3-4 d following
      BASELINE testing, participants returned to the lab for the first trial and
      ingested 354 ml of either JEE or decaffeinated coffee (DECAF), after which they
      performed a GXT and Wingate test. Criterion measures during the GXT included an
      assessment of peakVO2 at maximal exercise, as well as VO2 at 3 minutes and 10
      minutes post-exercise. Additionally, time-to-exhaustion (TTE), maximal RPE, mean
      heart rate (HR), mean systolic pressure (SBP), and mean diastolic blood pressure
      (DBP) were measured during each condition. Criterion measures for the Wingate
      included mean HR, SBP, DBP, peak power, and time to peak power (TTP).
      Participants then returned to the lab approximately one week later to perform the
      second trial under the same conditions as the first, except consuming the
      remaining coffee. Data were analyzed using a one way ANOVA (p < 0.05). Our
      results indicate that JEE significantly increased VO2 at 3 minutes post-exercise
      when compared to BASELINE (p = 0.04) and DECAF (p = 0.02) values, which may be
      beneficial in enhancing post-exercise fat metabolism.

PMID- 18067678
TI  - Comparison of APACHE II and Imrie Scoring Systems in predicting the severity of
      Acute Pancreatitis.
AB  - There has been an increasing amount of work worldwide in search for tests not
      only to be able to absolutely diagnose acute pancreatitis, but more importantly
      to prognosticate patients at admission. While the tests are still within the
      realm of research laboratories and involve complex computing and analytical
      methods, we believed that the already widely practiced methods of scoring needed
      to be verified in the Indian context. And, hence, the study.

PMID- 18067680
TI  - Delays in childhood immunization in a conflict area: a study from Sierra Leone
      during civil war.
AB  - BACKGROUND: Sierra Leone has undergone a decade of civil war from 1991 to 2001.
      From this period few data on immunization coverage are available, and conflict
      related delays in immunization according to the Expanded Programme on
      Immunization (EPI) schedule have not been investigated. We aimed to study delays
      in childhood immunization in the context of civil war in a Sierra Leonean
      community. METHODS: We conducted an immunization survey in Kissy Mess-Mess in the
      Greater Freetown area in 1998/99 using a two-stage sampling method. Based on
      immunization cards and verbal history we collected data on immunization for
      tuberculosis, diphtheria, tetanus, pertussis, polio, and measles by age group (0
      8/9-11/12-23/24-35 months). We studied differences between age groups and
      explored temporal associations with war-related hostilities taking place in the
      community. RESULTS: We included 286 children who received 1690 vaccine doses;
      card retention was 87%. In 243 children (85%, 95% confidence interval (CI): 80
      89%) immunization was up-to-date. In 161 of these children (56%, 95%CI: 50-62%)
      full age-appropriate immunization was achieved; in 82 (29%, 95%CI: 24-34%)
      immunization was not appropriate for age. In the remaining 43 children
      immunization was partial in 37 (13%, 95%CI: 9-17) and absent in 6 (2%, 95%CI: 1
      5). Immunization status varied across age groups. In children aged 9-11 months
      the proportion with age-inappropriate (delayed) immunization was higher than in
      other age groups suggesting an association with war-related hostilities in the
      community. CONCLUSION: Only about half of children under three years received
      full age-appropriate immunization. In children born during a period of increased
      hostilities, immunization was mostly inappropriate for age, but recommended
      immunizations were not completely abandoned. Missing or delayed immunization
      represents an additional threat to the health of children living in conflict
      areas.

PMID- 18067679
TI  - Malaria incidence and efficacy of intermittent preventive treatment in infants
      (IPTi).
AB  - BACKGROUND: Intermittent preventive antimalarial treatment in infants (IPTi) is
      currently evaluated as a malaria control strategy. Among the factors influencing
      the extent of protection that is provided by IPTi are the transmission intensity,
      seasonality, drug resistance patterns, and the schedule of IPTi administrations.
      The aim of this study was to determine how far the protective efficacy of IPTi
      depends on spatio-temporal variations of the prevailing incidence of malaria.
      METHODS: One thousand seventy infants were enrolled in a registered controlled
      trial on the efficacy of IPTi with sulphadoxine-pyrimethamine (SP) in the Ashanti
      Region, Ghana, West Africa (ClinicalTrial.gov: NCT00206739). Stratification for
      the village of residence and the month of birth of study participants
      demonstrated that the malaria incidence was dependent on spatial (range of
      incidence rates in different villages 0.6-2.0 episodes/year) and temporal (range
      of incidence rates in children of different birth months 0.8-1.2 episodes/year)
      factors. The range of spatio-temporal variation allowed ecological analyses of
      the correlation between malaria incidence rates, anti-Plasmodium falciparum
      lysate IgG antibody levels and protective efficacies provided by IPTi. RESULTS:
      Protective efficacy of the first SP administration was positively correlated with
      malaria incidences in children living in a distinct village or born in a distinct
      month (R2 0.48, p < 0.04 and R2 0.63, p < 0.003, respectively). Corresponding
      trends were seen after the second and third study drug administration.
      Accordingly, IgG levels against parasite lysate increased with malaria incidence.
      This correlation was stronger in children who received IPTi, indicating an effect
      modification of the intervention. CONCLUSION: The spatial and temporal variations
      of malaria incidences in a geographically and meteorologically homogeneous study
      area exemplify the need for close monitoring of local incidence rates in all
      types of intervention studies. The increase of the protective efficacy of IPTi
      with malaria incidences may be relevant for IPTi implementation strategies and,
      possibly, for other malaria control measures.

PMID- 18067681
TI  - Implementing evidence-based interventions in health care: application of the
      replicating effective programs framework.
AB  - BACKGROUND: We describe the use of a conceptual framework and implementation
      protocol to prepare effective health services interventions for implementation in
      community-based (i.e., non-academic-affiliated) settings. METHODS: The framework
      is based on the experiences of the U.S. Centers for Disease Control and
      Prevention (CDC) Replicating Effective Programs (REP) project, which has been at
      the forefront of developing systematic and effective strategies to prepare HIV
      interventions for dissemination. This article describes the REP framework, and
      how it can be applied to implement clinical and health services interventions in
      community-based organizations. RESULTS: REP consists of four phases: pre
      conditions (e.g., identifying need, target population, and suitable
      intervention), pre-implementation (e.g., intervention packaging and community
      input), implementation (e.g., package dissemination, training, technical
      assistance, and evaluation), and maintenance and evolution (e.g., preparing the
      intervention for sustainability). Key components of REP, including intervention
      packaging, training, technical assistance, and fidelity assessment are crucial to
      the implementation of effective interventions in health care. CONCLUSION: REP is
      a well-suited framework for implementing health care interventions, as it
      specifies steps needed to maximize fidelity while allowing opportunities for
      flexibility (i.e., local customizing) to maximize transferability. Strategies
      that foster the sustainability of REP as a tool to implement effective health
      care interventions need to be developed and tested.

PMID- 18067682
TI  - Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1,
      or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive
      modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding.
AB  - BACKGROUND: Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain
      can be accelerated by phorbol esters, compounds that act via protein kinase C
      (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We
      have previously demonstrated that application of phorbol esters or purified PKC
      potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network
      (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes
      responsible for shedding, known collectively as alpha-secretase(s). However,
      molecular identification of the presumptive "phospho-state-sensitive modulators
      of ectodomain shedding" (PMES) responsible for regulated shedding has been
      challenging. Here, we examined the effects on APP ectodomain shedding of four
      phorbol-sensitive proteins involved in regulation of vesicular membrane
      trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1. RESULTS: Overexpression of
      either phorbol-sensitive wildtype Munc13-1 or phorbol-insensitive Munc13-1 H567K
      resulted in increased basal APP ectodomain shedding. However, in contrast to the
      report of Rossner et al (2004), phorbol ester-dependent APP ectodomain shedding
      from cells overexpressing APP and Munc13-1 wildtype was indistinguishable from
      that observed following application of phorbol to cells overexpressing APP and
      Munc13-1 H567K mutant. This pattern of similar effects on basal and stimulated
      APP shedding was also observed for Munc18 and NSF. Eve-1, an ADAM adaptor protein
      reported to be essential for PKC-regulated shedding of pro-EGF, was found to play
      no obvious role in regulated shedding of sAPPalpha. CONCLUSION: Our results
      indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to
      meet essential criteria for identity as PMES for APP.

PMID- 18067683
TI  - Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila
      reveals a species-general network of aging and metabolic genes.
AB  - BACKGROUND: Several interventions increase lifespan in model organisms, including
      reduced insulin/insulin-like growth factor-like signaling (IIS), FOXO
      transcription factor activation, dietary restriction, and superoxide dismutase
      (SOD) over-expression. One question is whether these manipulations function
      through different mechanisms, or whether they intersect on common processes
      affecting aging. RESULTS: A doxycycline-regulated system was used to over-express
      manganese-SOD (MnSOD) in adult Drosophila, yielding increases in mean and maximal
      lifespan of 20%. Increased lifespan resulted from lowered initial mortality rate
      and required MnSOD over-expression in the adult. Transcriptional profiling
      indicated that the expression of specific genes was altered by MnSOD in a manner
      opposite to their pattern during normal aging, revealing a set of candidate
      biomarkers of aging enriched for carbohydrate metabolism and electron transport
      genes and suggesting a true delay in physiological aging, rather than a novel
      phenotype. Strikingly, cross-dataset comparisons indicated that the pattern of
      gene expression caused by MnSOD was similar to that observed in long-lived
      Caenorhabditis elegans insulin-like signaling mutants and to the xenobiotic
      stress response, thus exposing potential conserved longevity promoting genes and
      implicating detoxification in Drosophila longevity. CONCLUSION: The data suggest
      that MnSOD up-regulation and a retrograde signal of reactive oxygen species from
      the mitochondria normally function as an intermediate step in the extension of
      lifespan caused by reduced insulin-like signaling in various species. The results
      implicate a species-conserved net of coordinated genes that affect the rate of
      senescence by modulating energetic efficiency, purine biosynthesis, apoptotic
      pathways, endocrine signals, and the detoxification and excretion of metabolites.

PMID- 18067685
TI  - Group cognitive behavior therapy for Japanese patients with social anxiety
      disorder: preliminary outcomes and their predictors.
AB  - BACKGROUND: A number of studies have provided strong evidence for the use of
      cognitive behavior therapy (CBT) in the treatment of social anxiety disorder
      (SAD). However, all of the previous reports were from Europe and North America
      and it is unknown whether Western psychological therapies are effective for SAD
      in non-Western cultures. The present pilot study aimed to evaluate CBT program
      for SAD which was originally developed for Western patients, among Japanese
      patients. METHODS: Fifty-seven outpatients who participated in group CBT for SAD
      were evaluated using eight self-reported and one clinician-administered
      questionnaires to measure various aspects of SAD symptomatology at the beginning
      and at the end of the program. Pre- and post-treatment scores were compared and
      the magnitude of treatment effect was quantified as well based once on the
      intention-to-treat (ITT) and once among the completers only. We also examined
      baseline predictors of the CBT outcomes. RESULTS: Seven patients (12%) did not
      complete the program. For the ITT sample, the percentage of reduction was 20% to
      30% and the pre to post treatment effect sizes ranged from 0.37 to 1.01. Among
      the completers, the respective figures were 20% to 33% and 0.41 to 1.19. We found
      no significant pretreatment predictor of the outcomes. CONCLUSION: Group CBT for
      SAD is acceptable and can bring about a similar degree of symptom reduction among
      Japanese patients with SAD as among Western patients.

PMID- 18067684
TI  - When public action undermines public health: a critical examination of
      antifluoridationist literature.
AB  - BACKGROUND: The addition of the chemical fluorine to the water supply, called
      water fluoridation, reduces dental caries by making teeth more resistant to
      demineralisation and more likely to remineralise when initially decayed. This
      process has been implemented in more than 30 countries around the world, is cost
      effective and has been shown to be efficacious in preventing decay across a
      person's lifespan. However, attempts to expand this major public health
      achievement in line with Australia's National Oral Health Plan 2004-2013 are
      almost universally met with considerable resistance from opponents of water
      fluoridation, who engage in coordinated campaigns to portray water fluoridation
      as ineffective and highly dangerous. DISCUSSION: Water fluoridation opponents
      employ multiple techniques to try and undermine the scientifically established
      effectiveness of water fluoridation. The materials they use are often based on
      Internet resources or published books that present a highly misleading picture of
      water fluoridation. These materials are used to sway public and political opinion
      to the detriment of public health. Despite an extensive body of literature, both
      studies and results within studies are often selectively reported, giving a
      biased portrayal of water fluoridation effectiveness. Positive findings are
      downplayed or trivialised and the population implications of these findings
      misinterpreted. Ecological comparisons are sometimes used to support spurious
      conclusions. Opponents of water fluoridation frequently repeat that water
      fluoridation is associated with adverse health effects and studies are
      selectively picked from the extensive literature to convey only claimed adverse
      findings related to water fluoridation. Techniques such as "the big lie" and
      innuendo are used to associate water fluoridation with health and environmental
      disasters, without factual support. Half-truths are presented, fallacious
      statements reiterated, and attempts are made to bamboozle the public with a large
      list of claims and quotes often with little scientific basis. Ultimately,
      attempts are made to discredit and slander scientists and various health
      organisations that support water fluoridation. SUMMARY: Water fluoridation is an
      important public health initiative that has been found to be safe and effective.
      Nonetheless, the implementation of water fluoridation is still regularly
      interrupted by a relatively small group of individuals who use misinformation and
      rhetoric to induce doubts in the minds of the public and government officials. It
      is important that public health officials are aware of these tactics so that they
      can better counter their negative effect.

PMID- 18067686
TI  - Sensitization of catastrophic cognition in cognitive-behavioral therapy for panic
      disorder.
AB  - BACKGROUND: Cognitive model of panic disorder have proposed that panic attacks
      result from the catastrophic misinterpretation of certain bodily sensations.
      Cognitive-Behavioral Therapy (CBT) for panic disorder aims to change these
      catastrophic cognitions. CBT intervention successfully caused reduction of
      catastrophic cognitions and symptomatic improvement in the majority of cases.
      However there are some patients who fail to modify their catastrophic cognitions
      or rather experience an increase in them during CBT treatment. It is clinically
      and theoretically important to understand about cognitive sensitization of panic
      disorder during CBT sessions. The purpose of the present study is 1) to clarify
      the baseline characteristics of panic patients who would experience sensitization
      of their catastrophic cognitions through the CBT treatment, and 2) to examine the
      course of symptomatic changes for them. METHODS: Of ninety-five outpatients with
      panic disorder started the group CBT program for treatment of panic disorder,
      seventy-nine completer were classified as "cognitively sensitized (CS)" or
      "cognitive responding (CR)" or "no-responder" according to the difference of the
      Agoraphobic Cognitions Questionnaire score across treatment. We compared the CS
      and CR patients in terms of their baseline clinical characteristics. Then we
      assessed the symptomatic and functional changes for both groups. RESULTS: At the
      start of the CBT program, despite of the same degree of panic disorder severity,
      CS scored significantly lower on ACQ score than CR. CS also showed significantly
      lower score on anticipatory anxiety compared to CR. At the end of treatment CS
      showed significant improvement in severity of panic disorder, although the degree
      of improvement was smaller than that for CR. Then CS would progressively reduce
      their agoraphobic fear and avoidance, and would improve their functional
      impairment up to three month of follow-up. CONCLUSION: Panic patients who would
      experience sensitization of their catastrophic cognitions through the CBT
      treatment could nonetheless gradually improve. They showed a relatively low level
      of catastrophic cognition and anticipatory anxiety before starting the CBT
      program. We might conclude that temporary sensitization of catastrophic cognition
      may be necessary before improvement especially among those with initially low
      catastrophic body sensation fears and that we need not be concerned too much with
      temporary increase in catastrophic cognition in the process of CBT for panic
      disorder.

PMID- 18067687
TI  - Multiple microvessels extending from the coronary arteries to the left ventricle
      in a middle aged female presenting with ischaemic chest pain: a case report.
AB  - Possible ischaemic chest pain presentations are exceedingly common. Angiographic
      triage of clinical, electrocardiographic or biomarker positive presentations is
      increasingly feasible with the expansion of cardiac catheterization facilities.
      This management pattern often extends to problem patients with negative biomarker
      screens whose symptoms appear unstable. With invasive triage even very rare
      congenital or developmental coronary anomalies will be more frequently recognized
      although their relationship to ischaemia can be confounded by association. In
      this a case we report a woman with widespread direct coro-ventricular micro
      channel formation across the heart and an ischaemic presentation, despite
      angiographically normal epicoronary vessels. This pattern, while very rare, needs
      to be recognized as one possible phenotype in this very common clinical
      presentation.

PMID- 18067688
TI  - Do fluoroquinolones predispose patients to Clostridium difficile associated
      disease? A review of the evidence.
AB  - BACKGROUND: Clostridium difficile associated diarrhea (CDAD) is an important
      cause of hospital-acquired diarrhea, and increasingly of community-acquired
      diarrhea. The occurrence of CDAD in the hospitalized patient is associated with
      increased length of stay, morbidity, mortality, and healthcare costs. Exposure to
      antimicrobials is the single most important predisposing factor for acquiring
      CDAD. The data suggesting that fluoroquinolones are an important risk factor for
      CDAD is becoming stronger. Also, different fluoroquinolones may pose different
      risks for CDAD development. OBJECTIVES: The aim of this commentary is to
      summarize the literature as it relates to the role that fluoroquinolones may have
      in CDAD. METHODS: PubMed and Ovid MEDLINE were searched using the terms
      fluoroquinolones, ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin in
      combination with C. difficile, CDAD, pseudomembranous colitis and antibiotic
      associated diarrhea. RESULTS: The evidence for an association between
      fluoroquinolone use and CDAD, especially CDAD due to the hypervirulent NAP1
      strain or the polymerase chain reaction ribotype 027, is becoming stronger.
      CONCLUSIONS: Fluoroquinolones appear to predispose patients to CDAD. The data are
      suggestive but not conclusive. More studies are needed to define the role that
      fluoroquinolones play in the development of CDAD. Meticulous and enhanced
      infection control practices at all times and the judicious use of antimicrobials
      will help contain the epidemic of CDAD.

PMID- 18067689
TI  - The costs of Crohn's disease in the United States and other Western countries: a
      systematic review.
AB  - OBJECTIVE: To conduct a critical and systematic literature review of the costs of
      Crohn's disease (CD) in Western industrialized countries. RESEARCH DESIGN AND
      METHODS: Studies published in English that described the cost of CD in Western
      industrialized countries were identified using three major databases (Medline,
      EMBASE, and ISI Web of Science). Studies were reviewed and rated based on their
      relevance to cost of illness and the reliability of the estimates. All costs were
      adjusted for inflation to 2006 values. RESULTS: Estimated direct medical costs
      were $18,022-18,932 per patient with CD per year in the United States, and euro
      2898-6960 in other Western countries. Hospitalizations accounted for 53-66% of
      direct medical costs, with an average cost-per-hospitalization of $37,459 in the
      United States. Estimated indirect costs accounted for 28% of the total cost in
      the United States and 64-69% in Europe. Costs differed greatly by disease
      severity. Costs of patients with severe disease were 3- to 9-fold higher than
      patients in remission. Direct medical costs in the United States for patients in
      the top 25% of total costs averaged $60,582 per year; costs of patients in the
      top 2% averaged more than $300,000 per year. Combining prevalence rates, the
      total economic burden of CD was $10.9-15.5 billion in the United States and euro
      2.1-16.7 billion in Europe. LIMITATIONS: This review is limited by the research
      quality and variations of the individual studies reviewed, and only includes
      English articles. CONCLUSIONS: This updated literature synthesis demonstrated the
      substantial total cost burden of CD, of which hospitalizations accounted for more
      than half of direct medical costs.

PMID- 18067691
TI  - Intussusception in adults.

PMID- 18067692
TI  - Reconstructing the abdominal wall with a biocompatible patch.

PMID- 18067693
TI  - Osteitis pubis simulating a soft-tissue lesion.

PMID- 18067694
TI  - Hepatic portal venous gas from perforated sigmoid diverticulitis.

PMID- 18067695
TI  - Myositis ossificans traumatica of the hand.

PMID- 18067696
TI  - Ectopic breast tissue presenting as an anal polyp.

PMID- 18067697
TI  - Stromal tumour of the stomach.

PMID- 18067698
TI  - Rofecoxib associated with diaphragm disease.

PMID- 18067699
TI  - Gastric outlet obstruction.

PMID- 18067700
TI  - Lymphogranuloma venereum as a cause of rectal stricture.

PMID- 18067701
TI  - Leiomyoma of iliac bone.

PMID- 18067702
TI  - An unusual gastric tumour.

PMID- 18067703
TI  - [Some issues deserve consideration in sphincter-preserving operations of low
      rectal cancer].

PMID- 18067704
TI  - [New pattern of comprehensive treatment for rectal cancer: the ascendant
      neoadjuvant radiochemotherapy].

PMID- 18067705
TI  - [Lateral pelvic metastasis and micrometastasis in low rectal cancer].
AB  - OBJECTIVE: To study lateral pelvic metastasis and micrometastasis of low rectal
      cancer and elucidate their prognostic value. METHODS: Whole-mount slice and
      tissue microarray of dissected lateral pelvic specimen from 67 cases of low
      rectal cancer were examined, and the included cases were followed up. RESULTS:
      Twelve specimens were diagnosed as lateral metastasis, while another 10 were
      proved to bear micrometastasis. Most of the involved metastatic lymph nodes
      (82.9%) were smaller than 5 mm in diameter. Internal iliac, obturator regions and
      middle rectal root were more likely to be involved by tumors. Patients with
      lateral metastasis suffered more recurrence and poorer survival. CONCLUSIONS:
      Lateral pelvic metastasis could be observed in low rectal cancer and its
      incidence differed among lateral pelvic regions. Patients with lateral spread
      predisposed poor prognosis, thus underlies the value of pre/postoperative
      adjuvant therapy.

PMID- 18067706
TI  - [Effect of lateral lymph nodes dissection and autonomic nerve preservation in
      anterior resection for rectal cancer: 124 cases review].
AB  - OBJECTIVE: To investigate the clinical effect of lateral lymph nodes dissection
      and autonomic nerve preservation in anterior resection for rectal cancer.
      METHODS: One hundred and twenty-four patients with rectal cancer underwent
      anterior resection with lateral lymph nodes resection and autonomic nerve
      preservation. The patients were followed-up through post-operational
      questionnaire about the function of defecation, urination and sex after the
      operation. And post-operative survival was analyzed retrospectively. RESULTS:
      Urinary catheters were removed in 112 cases (90.3%) in 3 days post operation, the
      mean time of indwelling catheter was (58.3 +/- 2.1) h. Nineteen patients
      experienced fecal incontinence, 12 cases of them recovered through release
      training and one recovered spontaneously. Of the 98 questionnaire respondents, 61
      cases (62.3%) could erect normally, and 56 cases (57.1%) had normal sexual
      function. The max-micturition-desire urine volume was (401.2 +/- 23.1) ml and the
      residual urine volume was (28.2 +/- 2.2) ml. Five year survival rate of all the
      patients was 61.2%. CONCLUSIONS: Lateral lymph nodes dissection and autonomic
      nerve preservation in anterior resection for rectal cancer can decrease the post
      operative dysfunction of defecation, urination and sex life and does not affect
      the survival.

PMID- 18067707
TI  - [Therapeutic effects of transsphincteric surgery in treating rectal tumors: a
      report of 97 cases].
AB  - OBJECTIVE: To evaluate the role of transsphincteric surgery in local excision of
      mid and lower rectal tumors. METHODS: The clinical data of 97 patients with mid
      and lower rectal tumors underwent transsphincteric surgery from March 1990 to
      March 2007 were retrospectively analyzed. RESULTS: Ninety-one patients underwent
      partial proctectomy, and six underwent segmental proctectomy. Postoperative
      complications included wound infection in 5 (5.2%), fecal fistula in 4 (4.2%).
      Pathological examination showed rectal villous adenoma in 35 cases, rectal cancer
      in 50, rectal carcinoid and others in 12. The pathological stages of rectal
      cancers included Tis stage in 17 cases, T1 in 21, T2 in 7, T3 in 2, T4 in 3. The
      mean follow-up was 6.4 years (range, 2 months - 16 years). Three patients
      developed postoperative local recurrence (6.2%). The three- and five-year
      survival rate was 93.7% and 87.5%, respectively. There was no operation-related
      mortality, and no patient developed fecal incontinence. CONCLUSIONS: The
      transsphincteric surgery brings minor invasion, low operative risk and increased
      chance of sphincter preservation, which is suitable for treatment of mid and
      lower rectal tumors.

PMID- 18067708
TI  - [Clinical study of 231 cases of radical excision with sphincter preservation by
      casing anastomosis in low rectal cancer].
AB  - OBJECTIVE: To investigate the clinical efficacy, feasibility and safety of
      sphincter-preserving procedure by casing anastomosis of colon and rectal mucosa
      in low rectal cancer. METHODS: A retrospective analysis was carried out in 231
      cases of low rectal cancer performed casing anastomosis. RESULTS: One hundred and
      ninety-seven (197/231, 85.3%) cases were followed up, the median time of the
      follow up was 5.9 years (range, 2 months-14 years). Eight (3.4%) cases of stoma
      leak and 3 (1.2%) cases of stoma stenosis were found post operation. Defecating
      function recovered normally (1 - 3 times per day) in 12 - 24 weeks after
      operation in all patients. Local recurrence was found in 5.1% (10/197) of the
      cases. Hepatic and lung metastasis was found in 15.2% (30/197) and 2.5% (5/197)
      of the patients, respectively. The five-year survival rate was 71.6% totally.
      CONCLUSIONS: The casing anastomosis procedure with sphincter preservation is safe
      and efficacy for low rectal cancer. With the procedure, the anal function can be
      preserved well, stoma leak is decreased, and the five-year survival rate is the
      same as Miles operation.

PMID- 18067709
TI  - [Short-term results of sphincter-preserving operation with intersphincteric
      resection in low rectal cancer].
AB  - OBJECTIVES: To report the operative experience and sphincter-preserving results
      of total mesorectal excision (TME) combined with intersphincteric resection (ISR)
      in treating low rectal cancer. METHODS: From March 2000 to March 2007, 40 cases
      of patients with low rectal cancer were operated on: TME was performed
      transabdominally and ISR was performed transperineally. Postoperative anal
      function, local recurrence and metastasis were followed up. RESULTS: All of the
      operations were successfully completed. There was no death of operation occurred.
      The patients were followed-up for 3 months to 7 years (mean, 34 months).
      Favorable anal function was reserved in 39 patients with Kirwan grade of 1 to 3.
      Anastomotic leakage occurred in 1 case and wound infection in 2 cases. Two cases
      recurred locally after operation and one of them died. CONCLUSIONS: ISR can be
      safely performed in ultra-low rectal cancer, it preserves anal function well and
      offers radical cure.

PMID- 18067710
TI  - [Clinical analysis of therapeutic effects of sphincter-preserving operation and
      Miles operation for rectal cancer].
AB  - OBJECTIVE: To investigate and compare therapeutic effects of sphincter-preserving
      operation and Miles operation for rectal cancer. METHODS: A retrospective
      analysis was carried out in 572 cases of rectal cancer operations performed from
      January 1980 to December 2006. RESULTS: Sphincter-preserving operation was
      carried out in 403 cases and Miles procedure in 169 cases. The follow-up rate was
      76.2% (436/572) with a period of 0.5 - 25.0 years (median, 9.5 years). Local
      recurrence occurred in 6.3% (20/317) of sphincter-preserving operation and 7.6%
      (9/119) of Miles operation, the differences was not significant (chi2 = 1.3942, P
      > 0.05). Distal metastasis was found in 50 cases (15.7%) of sphincter-preserving
      operation and 19 cases (16.2%) of the Miles operation with no significant
      difference (chi2 = 0.6672, P > 0.05). There was no significant difference in five
      year survival rate between the two groups, with 67.8% in sphincter-preserving
      operation and 67.2% in Miles operation. CONCLUSIONS: Sphincter-preserving
      operations can improve the quality of life in rectal cancer although with the
      same five-year survival rate and recurrence rate as Miles operation. The
      operation for rectal cancer should be performed individually according to the
      location, the bionomics and the clinical stage.

PMID- 18067711
TI  - [Percutaneous radiofrequency ablation therapy with left single lung ventilation
      for liver carcinoma in the hepatic dome].
AB  - OBJECTIVE: To evaluate the advantages of percutaneous radiofrequency ablation
      (PRFA) therapy with contralateral single lung ventilation (SLV) for liver
      carcinoma in the hepatic dome (LCHD). METHODS: The clinical data of 10 patients
      (the SLV group) with LCHD consecutively treated from January to December 2006
      were retrospectively analyzed. And another 10 cases (the control group) with LCHD
      treated from January 2004 to December 2005 were selected with a strict inclusion
      criterion for compared test according to rules of same diagnosis, similar tumor
      bulk and site, same sex, similar age and liver function. The patients' ages and
      tumor diameters of the 2 groups were compared with t-test and the rates of
      complications and incomplete tumor ablation were compared with chi2-test.
      RESULTS: There was no statistical difference in ages and tumor diameters between
      the 2 groups (P > 0.05). The average number of radiofrequency ablation needle
      punctures in the SLV group was significantly less than the control group (3.4 +/-
      0.4 vs. 6.1 +/- 0.8, P < 0.01). There was no bronchial intubation related
      complications like hypoxemia, atelectasis, lung infection and no puncture related
      complications like pneumothorax, hemothorax, hemoperitoneum and bile leakage in
      the SLV group. Two cases in the control group had complications including
      pneumothorax (n = 1) and pleural effusion (n = 1). There was no mortality in the
      2 groups. Though the rate of incomplete tumor necrosis in the SLV group was not
      statistically lower than that in the control group (10% vs. 40%), the occurrence
      rate of the undesirable event (complication and incomplete tumor necrosis) of the
      SLV group was significantly lower than that of the control group (10% vs. 60%, P
      < 0.05). The durations and costs of operating procedure were not significantly
      different between the 2 groups. CONCLUSION: Left SLV makes PRFA for LCHD more
      efficient, effective and safe.

PMID- 18067712
TI  - [Clinical effects of subcutaneous tunnel hepatocholangioplasty on the treatment
      of hepatolithiasis].
AB  - OBJECTIVE: To evaluate the therapeutic effect of subcutaneous tunnel
      hepaticoplasty on the treatment of hepatolithiasis. METHODS: The early
      complications and clinical effects of 99 hepatolithiasis cases who underwent
      subcutaneous tunnel hepaticoplasty from January 1993 to August 2006 were analyzed
      retrospectively. The stones of 28 (28.3%) patients were in the left lobe, 24.2%
      (24/99) in the right, and 47.5% (47/99) in bilateral lobe. Sixty-six patients
      (66.7%) had both stones and biliary strictures. During the procedure, a portion
      of the liver habouring stone was resected if necessary. The hepatic duct and
      strictures were opened, the stones were removed, and the porta hepatis was
      repaired by one end of a segment of jejunum. The other end of the jejunum was set
      subcutaneously. The gall bladders of 27 patients (27.3%) were used as
      subcutaneous tunnel instead. RESULTS: Ninety-five out of ninety-nine cases were
      followed up with an average of 4.2 years (1 month to 13.5 years). The rates of
      residual stone, recurrent stone and cholangitis were 23.2% (23/99), 20.0% (19/95)
      and 14.7% (14/95) respectively. Postoperatively, 34 cases who had residual or
      recurrent stones were underwent lithotomy by choledochoscope through the
      subcutaneous blind loop and the achievement ratio was 91.2% (31/34). CONCLUSIONS:
      Subcutaneous tunnel hepatocholangioplasty decreases the relapsing cholangitis
      effectively, and makes an easy way to take out residual or recurrent stones.

PMID- 18067713
TI  - [Ultrasound-guided core needle biopsy in the diagnosis of breast lesions].
AB  - OBJECTIVE: To evaluate the accuracy and utility of ultrasound-guided core needle
      biopsy (CNB) in the diagnoses of breast lesions. METHODS: The clinical data of
      2152 consecutive breast lesions examined by CNB were reviewed. The histological
      agreement between core pathology and subsequent excision pathology was studied.
      The benign diseases without repeat biopsy were followed up. RESULTS: There were
      1461 cancers in final diagnosis among 2152 breast lesions, 1339 cancers were
      diagnosed by CNB. The false-negative rate of CNB was 3.5% (51/1461), and the
      underestimation rate was 4.9% (71/1461). In the repeat biopsy, carcinoma was
      found in 17 (50.0%) of 34 atypical ductal hyperplasia lesions and 25 (46.3%) of
      54 papillary lesions. In 1461 cancers, the false-negative rate of ultrasound
      guided CNB (2.1%, 22/1068) was significantly lower than that of free-hand-guided
      CNB (7.4%, 29/393) (P < 0.05). The false-negative rate of two special doctors for
      CNB (1.2%, 8/681) was significantly lower than that of other doctors (5.5%,
      43/780) (P < 0.05). In 738 of benign lesions, 417 cases were excised and 50
      malignant lesions were found, 205 cases were followed up by 2 - 29 months
      (median, 10.2 months), and one malignant lesion was found. CONCLUSIONS:
      Ultrasound-guided core needle biopsy with histopathological assessment is an
      accurate method in diagnosis of breast lesions. Excisional biopsy is required to
      the high-risk lesions in CNB.

PMID- 18067714
TI  - [Balloon dilation alone in treatment of arteriosclerotic stenosis or occlusions
      of femoropopliteal arteries].
AB  - OBJECTIVE: To evaluate the use and efficacy of balloon dilation in
      arteriosclerotic stenosis or occlusions of femoropopliteal arteries. METHODS:
      Thirty patients (27 men, 3 women, age from 44 to 78 years, mean 70) with
      arteriosclerotic stenosis or occlusion of femoropopliteal arteries received
      balloon dilation. Thirty-one balloons, which included 3 common balloons, 16
      cutting balloons, 10 "deep" balloons and 2 small balloons, were used. Follow-up
      surveillance featured periodic physical examination and duplex scanning. RESULTS:
      In all 30 patients, the technique success was reached only with 6 minor
      dissections. Angiography after dilation showed that the treated vessels were all
      patent with a < 20% stenosis remaining in any given lesions. After treatment and
      over a follow-up of 1 to 17 months (mean 6 months), the symptoms were relieved
      and all treated vessels were patent except 1 patient (3.3%) who had a gangrene
      foot and received limb amputation. CONCLUSION: Balloon dilation has a comparative
      ratio of one-stage success and short-term patency. Some special balloons seem to
      have a promising future in the management of femoropopliteal arterial
      arteriosclerotic lesions.

PMID- 18067715
TI  - [Pudendal-thigh flap: anatomic basis and application in repairing and
      reconstructing male perineal region].
AB  - OBJECTIVE: To investigate the anatomic feature of pudendal-thigh flap and to
      provide anatomic guide for clinical design and application of the flap in
      repairing and reconstructing male perineal region. METHODS: The clinical anatomy
      of blood supply and refluence and nerve innervation of the perineal region in 15
      male cadavers (30 sides) were investigated. Then reasonable flaps were designed
      for male patients needing repair and reconstruction of the perineal regions based
      on the anatomic findings. RESULTS: Perineal region has adequate arterial blood
      supply, abundant venous refluence and reliable nerve innervation. The area has
      multi-source blood supplies: external pudendal artery, anterior cutaneous
      branches of obturator artery, bole and lateral branch of arteriae scrotales
      posteriores. The locations of the arteries were mainly uniform in the 30 sides.
      Three vasoganglion composed by these arteries and their branches connecting
      superior, central and inferior parts of the flap. In the 23 cases, the largest
      flap was 17 cm x 9 cm, and the smallest was 8 cm x 5 cm. The flaps survived and
      recovered well, with perfect appearance and sensation. The patients were all
      satisfied with the operation results. CONCLUSIONS: The pudendal-thigh flap has
      abundant blood supply. It can be incised conveniently and covers donor sites
      well. The flap can be used to repair and reconstruct male perineum with ideal
      appearance and sensation.

PMID- 18067716
TI  - [Expression and clinical significance of matrix metalloproteinase in gastric
      stromal tumor].
AB  - OBJECTIVE: To investigate the expression and clinical significance of matrix
      metalloproteinase (MMP) in gastric stromal tumor (GST). METHODS: MMP-2 and MMP-9
      expression were determined by immunohistochemistry in tumor tissues in 44
      patients with GST, and their relationship with clinicopathologic factors of the
      neoplasm was also investigated. RESULTS: MMP-2 and MMP-9 were expressed in the
      cytoplasm in 84.1% (37/44) and 81.8% (36/44) of tumors, respectively. The
      positive rates of MMP-2 and MMP-9 increased significantly in parallel to the
      increase in tumor malignancy (P < 0.05) and associated with pattern of tumor
      growth, tumor size, and centre necrosis (P < 0.05). In addition, there was a
      statistically significant positive correlation between the expression of the two
      markers in GST (r = 0.6523, P < 0.05). Furthermore, the 5-year postoperative
      survival rates of patients with positive expressions of MMP-2 and MMP-9 were
      significantly lower than those of patients with negative expressions of the two
      markers (P < 0.05). CONCLUSION: Over expression of MMP-2 and MMP-9 can be served
      as objective markers to judge the malignant degree and, to predict the prognosis
      of patients with GST.

PMID- 18067717
TI  - [Relationship between changes of serum concentrations of antiangiogenic factors
      and disease progression in patients of pancreatic carcinoma].
AB  - OBJECTIVE: To investigate the relationship between TSP-1, Angiostatin and
      Endostatin serum concentrations and progression of pancreatic adenocarcinoma.
      METHODS: Fifty-six patients with suspected pancreatic cancer were enrolled in the
      study and divided into resectable group (n = 32) and unresectable group (n = 24)
      according to evaluation and staging with dual phase helical CT. Histopathologic
      examinations included postoperative final pathology and preoperative fine needle
      biopsies. Peripheral blood concentrations of antiangiogenic factors Angiostatin,
      Endostatin and TSP-1 were detected by using ELISA methods, selecting samples of
      health people as a control. RESULTS: Serum concentrations of antiangiogenic
      factors in pancreatic cancer group were significantly higher than those in health
      group (P < 0.01). Serum concentrations of Endostatin, Angiostatin and TSP-1 were
      significantly increased in unresectable group, and highly expressed in patients
      whom tumor sizes were greater than 2 cm and tumor invaded peripancreatic great
      vessels (P < 0.05). After operation, serum concentrations of Endostatin,
      Angiostatin and TSP-1 significantly decreased (P < 0.05). There were no
      significant difference between I, II stage group and III, IV group. CONCLUSIONS:
      Detection of serum concentrations of antiangiogenic factors may be used to
      evaluate the resectability of pancreatic cancer and may play important roles in
      growth, invasion and metastasis of pancreatic cancer.

PMID- 18067718
TI  - [Melanoma differentiation associated gene-7 and interleukin-24 selectively
      induces growth arrest and apoptosis in hepatocellular carcinoma cell lines in
      vitro].
AB  - OBJECTIVE: To investigate the effect of melanoma differentiation associated gene
      7/interleukin-24 (mda-7/IL-24) on the hepatocellular carcinoma cell lines and
      normal liver cell line in vitro. METHODS: Hepatocellular carcinoma cell lines
      HepG2, SMMC7721, Hep3B, MHCC97L, M6 and normal liver cell line L02 were infected
      with Ad.mda-7. The gene expression of mda-7/IL-24 in these cell lines was
      confirmed by RT-PCR and ELISA assay. MTT assay and flow cytometry were used to
      study tumor cell proliferation and cell cycle in vitro. Hoechst staining and
      cytometry assay after Annexin-V and PI staining were studied to indicate the
      apoptosis effect. RESULTS: It was confirmed by RT-PCR that the exogenous mda-7/IL
      24 gene expressed in all of these cells. The mda-7/IL-24 protein product was
      confirmed by assaying the supernatant with ELISA. MTT and apoptosis test
      indicated mda-7/IL-24 can induce the hepatocellular carcinoma cell lines growth
      suppression, apoptosis in vitro but not in normal liver cell line L02, cell cycle
      test revealed mda-7/IL-24 can block cancer cell lines in G2/M but not in L02.
      CONCLUSIONS: mda-7/IL-24 selectively induces growth suppression, apoptosis in
      hepatocellular carcinoma lines but not in normal liver cell in vitro.

PMID- 18067719
TI  - [Spontaneous response and mechanism to ischemia in diabetic mouse].
AB  - OBJECTIVE: To investigate the spontaneous response and its mechanism of type 2
      diabetes mouse to surgical induced hind limb ischemia. METHODS: Forty mice were
      randomly divided into two groups, one was fed with normal chow, and another was
      fed with high fat diet. Twelve weeks later, mice were surgical induced to hind
      limb ischemia. Blood flow was monitored. Four weeks later, mice were sacrificed
      and muscle tissues were harvested for histological detection, Western Blot, ELISA
      and RT-PCR examination respectively. RESULTS: Spontaneous restoration of blood
      flow was significantly slow down in type 2 diabetic mice with lower level of
      vascular density in ischemic muscles. VEGF signaling pathway was impaired
      although the VEGF levels were increased in diabetes. CONCLUSIONS: The spontaneous
      response to ischemia was attenuated with an abnormal reaction of VEGF signaling
      pathway in the setting of type 2 diabetes mellitus.

PMID- 18067728
TI  - [Secondary discussion of surgical treatment for spinal tuberculosis].

PMID- 18067720
TI  - [Effect of ethyl pyruvate on renal high mobility group box-1 protein expression
      and acute kidney injury in rats with delayed resuscitation after thermal injury].
AB  - OBJECTIVE: To investigate the effect of ethyl pyruvate (EP) on high mobility
      group box-1 protein (HMGB1) expression in renal tissue and acute kidney injury in
      rats with delayed resuscitation after thermal injury. METHODS: Seventy-eight
      Wistar rats subjected to 30% total body surface area full-thickness thermal
      injury followed with delayed resuscitation were divided into 3 groups: sham group
      (n = 18), injury group (n = 30) and EP group (n = 30). Renal tissue and blood
      samples were harvested to determine HMGB1 mRNA as well as its protein expression
      and renal function parameter at the 8, 24, 72 h post the "injury". HMGB1 mRNA was
      semi-quantitatively measured by reverse transcription polymerase chain reaction
      taking GAPDH as an internal standard, and HMGB1 protein expression was determined
      by Western blot and immunohistochemistry. Blood urea nitrogen (BUN) levels were
      measured with automatic biochemistry analyzer. The pathological changes of renal
      tissues were examined using HE staining. RESULTS: Compared with sham controls,
      both mRNA and protein expressions of HMGB1 in injury group were significantly
      enhanced in kidneys at 8 - 72 h after thermal injury (P < 0.05), meanwhile serum
      BUN levels were markedly increased (P < 0.05). Compared with injury group, the
      renal HMGB1 mRNA and protein expressions were markedly down-regulated in EP group
      at 8 h, 24 h and 72 h post injury (P < 0.05), respectively, and meanwhile serum
      BUN levels were reduced significantly (P < 0.05). Inflammatory cell infiltration
      was found in renal tissues following injury, and kidney injury was markedly
      alleviated after treatment with EP. CONCLUSIONS: It indicated that HMGB1 appears
      to be involved in the pathogenesis of post-burn acute kidney injury. Treatment
      with EP reduces renal HMGB1 expression, and protects against acute kidney injury
      secondary to delayed resuscitation after major burns.

PMID- 18067729
TI  - [The principle of individualized synthetical therapy to spinal tuberculosis].

PMID- 18067730
TI  - [Perioperative complications of single-stage surgical management for spinal
      tuberculosis].
AB  - OBJECTIVE: To analyze the causes of perioperative complications of single-stage
      surgical management for spinal tuberculosis. METHODS: One hundred and twenty
      patients with thoracic, lumbar and lumbosacral spinal tuberculosis were treated
      by single-stage surgical management from January 1997 to January 2006 in our
      unit, including seventy-five males and forty-five females. The mean age was 34.5
      (range 17 to 68) years old. The lesion ranged from T(6) to S(1). The anterior
      procedures of anterior debridement, interbody fusion and anterior fixation were
      carried out in sixty-five cases, posterior procedures in twenty-six cases, and
      combined anterior and posterior procedures in twenty-nine cases, respectively.
      The complications that occurred during surgical procedure and 1 month after
      operation were recorded. Underlying causes were analysed. RESULTS: There were 10
      cases (8.3%) were recorded of mild to severe complications during perioperative
      period in 120 patients. The complications and underlying causes were as follows:
      (1) A patient died from liver failure and blood coagulation dysfunction after
      operation due to inappropriate surgical timing (n = 1), in which case the patient
      with lumbosacral spinal tuberculosis also suffered from alcoholic liver sclerosis
      and dysfunction. (2) False diabetes insipidus (n = 1) and deep vein thrombosis of
      lower limbs (n = 1) occurred as result of surgical trauma. (3) Tear of iliac vein
      (n = 1) occurred with lumbosacral spinal tuberculosis because of unclear
      anatomical relationships when anterior debridement was performed. Injury of
      lumbar nerve roots (n = 3) and hemothorax (n = 1) also occurred due to
      mispractice of surgical procedures. (4) Paralysis intestinal obstruction and
      hypokalemia (n = 2) occurred after anterior procedures for lumbar spinal
      tuberculosis as a result of other reasons. CONCLUSIONS: Improper perioperative
      care will lead to complications of single-stage surgical procedures for spinal
      tuberculosis. Emphasis should be put on preoperative evaluation, surgical
      planning, and postoperative caring for prevention of complications.

PMID- 18067731
TI  - [Surgical treatment of spinal tuberculosis in aged].
AB  - OBJECTIVE: To investigate perioperative features and results of surgical
      treatment of spinal tuberculosis in aged. METHODS: Review the clinical data of 36
      aged with spinal tuberculosis from May 1998 to June 2005 retrospectively. The
      average age was 70.2 years. The sites of infection included 3 cervical, 9
      thoracic, 13 thoracolumbar and 11 lumbar. 28 patients suffered 1 or more
      complications at least and among of them, there were 18 patients have cerebral or
      heart vascular disease, 16 patients have diabetes mellitus. Before operation, all
      patients consulted with internal stuff for the proper treatment of concomitant
      disease. The surgical procedures include: CT guided percutaneous catheter
      drainage in 3 patients, anterior debridement and bony grafting with anterior
      instrumentation fixation in 12 patients, anterior debridement and bony grafting
      with posterior fixation in 5 patients, posterolateral costotransversectomy
      debridement and interbody fusion with posterior fixation in 7 patients, posterior
      debridement and posterior fixation in 9 patients. The mean followed-up period was
      3 years and 10 months (from 1.5 to 6 years). RESULTS: One died at two week after
      the operation. Tuberculous infection was controlled in other patients and no
      recurrence. Two patients died because of myocardial infarction and cerebral
      hemorrhage respectively at 1.5 and 2.5 years after operation. Bone fusion was
      achieved in 31 patients. The deformity was partial corrected at the final follow
      up. Among 20 cases with neurologic deficit, 11 cases were completely recovered, 5
      cases were partly improved. CONCLUSIONS: If the associated disorders and
      postoperative complications are properly handled, aged patients can endure
      surgical treatment for spinal tuberculosis. Instrumentation fixation provides
      adequate stability and promote recovery.

PMID- 18067732
TI  - [Analysis of failure reasons for postoperative patients of spinal tuberculosis
      complicated with paraplegia of 32 cases].
AB  - OBJECTIVE: To discuss the failure reasons of operation for spinal tuberculosis
      complicated with paraplegia and methods of the second operation. METHODS: Spinal
      tuberculosis paraplegic patients (18 males, 14 females) were reviewed
      retrospectively. They have been treated with failing decompressive surgery from
      January 2001 to December 2006. Seventeen patients received anterior debridement
      surgery via transpleural approach while the other 15 patients received
      posterolateral decompression surgery via costotransverse approach. Twenty-two
      patients got chemotherapy after the surgery. RESULTS: Twenty-three patients were
      treated by anterior debridement, decompression and graft placement via
      transpleural approach (9 received the single-stage posterior instrumentation).
      Five patients received posterolateral debridement and decompression via
      extrapleural approach. Two patients, recur focus be eliminated. Two patients were
      given sinus debridement surgery alone. All patients were given anti-tuberculosis
      chemotherapy. The paraplegia was recovered completely in 26 patients, and partly
      in 5 patients. CONCLUSIONS: Inadequate treatment results in defeated operative.
      The proper selection of operative modalities and timing on the basis of
      systematically anti-tuberculosis chemotherapy remains the best mode of therapy
      for spinal tuberculosis complicated with paraplegia. And it is also essential to
      choose a radical debridement surgery to decompress the spinal cord and to
      reconstruct the stability of spine.

PMID- 18067735
TI  - [Comparative analysis of pedicle screw versus hybrid instrumentation in posterior
      spinal correction of adolescent idiopathic scoliosis].
AB  - OBJECTIVE: To compare the effect of posterior correction and fusion between
      segmental pedicle screw instrumentation with hybrid constructs in adolescent
      idiopathic scoliosis (AIS). METHODS: Study the clinical data of 40 AIS patients
      retrospectively. They were underwent posterior fusion and be distributed into two
      group, group A was hybrid instrumentation (20 cases) and group B was pedicle
      screw instrumentation (20 cases). Compared therapy effect, operative time,
      intraoperative blood loss. RESULTS: The average major curve correction was 82.4%
      in the screw group and 71.8% in the hybrid group (P = 0.004). After one to three
      years follow-up, major curve correction was 77.0% and 62.5% respectively (P =
      0.001). Average apical vertebral derotation showed 63% correction in the screw
      group and 32% in the hybrid group (P = 0.001). There was no statistical
      significance between two group in thoracic sagittal correction, the lowest
      instrumented vertebra below the lower end vertebra, trunk shift, operative time,
      and average estimated blood loss. There were no neurologic complications related
      to hybrid or pedicle screw instrumentation. CONCLUSION: Pedicle screw
      instrumentation was significantly better than hybrid constructs.

PMID- 18067736
TI  - [Evaluation of surgical technique and indication on descending aortic aneurysms].
AB  - OBJECTIVE: To evaluate the surgical technique and indication on descending aortic
      aneurysms. METHODS: From January 1996 to June 2006, 41 patients with descending
      aortic aneurysm underwent operation, including DeBakey type III dissection in 26,
      false aneurysm in 6, true aneurysm in 4, and residual or newly complicated type
      III dissection after the surgery of Marfan syndrome in 5. Operations were
      performed by left heart bypass in 9, femoral-femoral bypass in 7, pulmonary
      femoral bypass in 2, and deep hypothermic circulatory arrest in 23. The whole
      thoracic descending aorta was replaced in 15, and intercostal arteries were
      reimplanted in 12. RESULTS: One patient died of acute renal failure with the
      hospital mortality 2.4%. Main complications: respiratory dysfunction in 6, renal
      dysfunction in 6, recurrent nerve injuries in 4, chylothorax in 2, and no
      paraplegia. CONCLUSIONS: Surgical intervention of descending aortic aneurysm
      still has its unique advantages and indications; surgical safety is markedly
      improved by the use of deep hypothermic circulatory arrest.

PMID- 18067737
TI  - [Aneurysm repair in vitro and renal revascularization and renal autogenous
      transplantation for complex renal artery aneurysm in solitary kidney].
AB  - OBJECTIVE: To discuss the safety and feasibility of aneurysm repair in vitro and
      renal revascularization and renal autogenous transplantation for complex renal
      artery aneurysm in solitary kidney. METHODS: A complex hilar renal artery
      aneurysm involving the bifurcation of renal artery and its branches in a solitary
      left kidney was diagnosed by computed tomography angiography (CTA). After
      temporary nephrectomy, aneurysm repair in vitro and renal revascularization were
      done with the kidney protected by hypothermia and continuous perfusion with
      preservation solution, and then the kidney was replanted into the right iliac
      fossa. RESULTS: The operation was done successfully and there were no significant
      perioperative complications. Although a serum creatinine level temporarily
      exceeded above 200 micromol/L after the surgery, it recovered gradually within
      half a month. CTA two weeks later demonstrated patent reconstructed renal
      arteries and its branches and patent renal vein in the right iliac fossa, and
      also a patent reconstructed ureter. CONCLUSIONS: This technique is safe and
      feasible to manage complex renal artery aneurysm in solitary kidney and provide
      an alternative for similar complex renal diseases.

PMID- 18067739
TI  - [Reconstruction of extended skin defect after the radical resection procedure for
      penile scrotum skin cancer].
AB  - OBJECTIVES: To investigate the reconstruction of skin defect after extended
      resection of malignant skin tumor in or adjacent to the genitals, and to
      investigate the recovery of the function of urinary system and sexual intercourse
      after the operation. METHODS: From February 1998 to August 2006, 17 patients with
      carcinoma of sweat gland or Paget's disease in or adjacent to the genitals were
      given standard radical resections including groin lymph node dissections. The
      deformation of penis were corrected with the split-thickness skin grafts.
      RESULTS: A large split-thickness skin to cover the wound gave a good result. More
      than 95% of the skin survived, and the shape and function were perfect.
      CONCLUSIONS: It is a simple and easy way to repair the skin defect. And the
      patients have a normal shape and function of genitals. The erectile function and
      the ability of sexual intercourse is good.

PMID- 18067740
TI  - [Study of prognostic factors of ureter cancer].
AB  - OBJECTIVE: To evaluate the prognostic factors of ureter transitional cell
      carcinoma (TCC). METHODS: Between January 2001 and December 2005 133 TCC patients
      were treated. And the data was retrospectively analyzed. RESULTS: A mean age of
      the 133 patients was 68 years (range 43 - 87 years) at diagnosis. Altogether the
      non-invasive ureter TCC was found in 42 patients (31.6%) and the invasive ureter
      TCC in 91 patients (68.4%). Invasive ureter TCC growth was more common in
      distally located tumors (82.5%) compared to mid (62.5%) and proximal ureter
      (47.1%). Tumor stage, grade and location of the tumor were all correlated with
      disease specific survival in a univariate analysis. In a multivariate Cox
      analysis, tumor stage and grade were significantly associated with disease
      specific survival. CONCLUSIONS: More invasive tumors are found in ureter than in
      bladder. Ureter cancer is more frequently found in the distal part. Distally
      located ureteral tumors are more likely invading into the muscular cell layers
      compared to proximally located tumors. Tumor stage and grade are still the more
      important prognostic factors for ureter TCC.

PMID- 18067741
TI  - [Effect of genetic polymorphism of MTNR1A gene on adolescent idiopathic
      scoliosis].
AB  - OBJECTIVE: To investigate whether the MTNR1A gene promotor polymorphism
      (rs2119882) are associated with the occurrence or curve severity of adolescent
      idiopathic scoliosis (AIS). METHODS: 226 AIS patients and 277 normal controls
      were recruited. The maximum Cobb angles were recorded in AIS patients. PCR-RFLP
      was used for the genotyping. RESULTS: The genotype and allele frequency
      distribution were comparable between AIS and normal control, the mean maximum
      Cobb angle of different genotypes of rs2119882 were similar with each other among
      AIS patients. CONCLUSION: The MTNR1A gene promoter polymorphism was neither
      associated with the occurrence nor the curve severity of AIS.

PMID- 18067742
TI  - [Study of growth inhibition of lung cancer cells by siRNA targeting mutant K-ras
      gene in vitro and in vivo].
AB  - OBJECTIVE: To study the inhibitory effect of mutant K-ras gene depletion by small
      interfering RNA on the growth of lung cancer cell line-H441 cells in vitro and in
      vivo. METHODS: One pair of 63 bp reverse repeated sequence targeting mutant K
      ras(V12) mRNA spaced by 9 bp nucleotide were synthesized and inserted into
      plasmid pSilencer3.1 eukaryotic expression vector. After transient and stable
      transfection into H441 cells, the mutant K-ras mRNA and protein level were
      measured by RT-PCR and Western blotting, and the H441 cells proliferation was
      measured by MTT method, and the apoptosis rate was detected by flow-cytometry.
      H441 cells treated with pSilencer3.1-K-ras(V12) were transplanted subcutaneously
      in nude mice and their tumorigenesis ability was observed. RESULTS: The
      recombinant plasmid pSilencer3.1-K-ras(V12) was successfully constructed by
      sequencing. The introduction of pSilencer3.1-K-ras(V12) was showed to efficiently
      and specifically inhibit the expression of K-ras(V12) gene according to the
      results of RT-PCR and Western blotting (P < 0.01, as compared with controls). The
      inhibitory effect on cell proliferation was confirmed by MTT test (P < 0.05, as
      compared with controls). Apoptosis rate of H441 cells treated with pSilencer3.1-K
      ras(V12) was significantly higher than that of the control cells (P < 0.01). The
      test in vivo showed that downregulation of K-ras(V12) expression in H441 cells
      apparently affected their ability to form tumors in nude mice. CONCLUSIONS: siRNA
      targeting mutant K-ras mRNA can specifically suppress the expression of mutant K
      ras gene in H441 cells, and therefore has a substantially inhibitory effect on
      cell proliferation in vitro and in vivo, it provides a new method and material to
      the gene therapy of lung cancer.

PMID- 18067743
TI  - [Micro-CT evaluation and histological analysis of screw-bone interface of
      expansile pedicle screw in osteoporotic sheep].
AB  - OBJECTIVE: To investigate the properties of screw-bone interface of expansive
      pedicle screw (EPS) in osteoporotic sheep using micro-CT and histology. METHODS:
      Six female sheep with bilateral ovariectomy-induced osteoporosis were employed in
      this experiment and were randomly assigned into 2 groups: A and B. After EPS
      insertion in each femoral condyles, sheep in group A were bred for 3 months,
      while those in group B 6 months. Femoral condyles with EPS were 3D-imaged and
      reconstructed by micro-CT. Histology was evaluated thereafter. RESULTS: The
      trabecular microstructure was denser at the screw-bone interface than in the
      distant parts in expansive section, especially within spiral marking. In the non
      expansive section, however, there was no significant difference between the
      interface and the distant parts. The regions of interest (ROI) adjacent to EPS
      were reconstructed and analyzed by micro-CT using the same thresholds. The 3D
      parameters generated, including tissue mineral density (TMD), bone volume
      fraction (BVF, BV/TV), bone surface/bone volume (BS/BV) ratio, trabecular
      thickness (Tb.Th), and trabecular separation (Tb.Sp), were significantly better
      in expansive than in non-expansive sections (P < 0.05). Histologically, newly
      formed bone trabeculae crawled along the expansive fissures and into the center
      of EPS. The newly formed bones, as well as the bone at the bone-screw interface,
      closely contacted the EPS and constructed four compartments. CONCLUSIONS: Based
      on micro-CT and histological evaluation, the study suggest that EPS can
      significantly provide stabilization in osteoporotic cancellous bone.

PMID- 18067744
TI  - [The regulation of hypoxia inducible factor-1alpha on osteoblast function in
      postmenopausal osteoporosis].
AB  - OBJECTIVE: To study the regulation of hypoxia inducible factor-1alpha (HIF
      1alpha) on osteoblast function in postmenopausal osteoporosis. METHODS: From
      October 2004 to May 2006, Cre-Loxp recombinase was used to create mice which the
      HIF-1alpha gene in osteoblasts was conditional knock-out, 24 female wild-type
      (WT) mice and 24 female conditional knock-out (CKO) mice of 3 months old were
      operated on ovariotomy. At 0,4,8 weeks after operation, bone histomorphometry
      parameters were measured with computer image analysis in HE stain sections and in
      tetracycline bone double labeling fluorescence sections; Bone density and the
      trabecular bone architecture parameters were measured by Micro-CT; The mRNA
      expression of vascular endothelial growth factors (VEGF), RunX2, OC, ALP were
      detected with quantitative RT-PCR; The protein expression of VEGF and RunX2 were
      detected with Western-blotting. RESULTS: In CKO mice, the trabecular number,
      volume, thickness, bone density, mineral apposition rate (MAR), the expression of
      VEGF, RunX2, OC, ALP on mRNA level and the expression of VEGF, RunX2 on protein
      level decreased significantly compared with WT mice especially in 8 weeks after
      operation. CONCLUSIONS: The bone formation ability of osteoblasts in CKO mice was
      reduced compared with WT mice after ovariotomy. HIF-1alpha can regulate the bone
      formation ability of osteoblasts in postmenopausal osteoporosis.

PMID- 18067746
TI  - [Construction and identification of human bone morphogenetic protein-7
      recombinant adeno-associated virus type 2 vector and its expression in bone
      mesenchymal stem cells].
AB  - OBJECTIVES: To facilitate gene therapy research using recombinant adeno
      associated virus type 2 (rAAV2) vector as gene transfer vehicle, and to construct
      a rAAV2 based vector carrying bone morphogenetic protein-7 (BMP7) and observe its
      expression in bone mesenchymal stem cells. METHODS: The coding sequence (1.3 kb)
      of BMP7 was amplified by polymerase chain reaction (PCR) from the pcDNA1.1(+)
      plasmid containing the human BMP-7 cDNA. After purified, the gene fragment was
      cloned into a plasmid pUC18 and termed plasmid pUC18-hBMP7. The recombinant pUC18
      hBMP7 was digested by Kpn I and Sal I and further ligated to the pSNAV by T4DNA
      ligase. The resultant plasmid PSNAV-hBMP7 was transformed into DH5a Escherichia
      coli, and positive colonies were screened by PCR and digest with restriction
      enzyme to identify the correct recombinant clones. BHK-21 cells were transfected
      with the purified pSNAV-BMP7 plasmid according to a standard calcium phosphate
      precipitation method. The cells were then cultured in selection media containing
      800 micro g/ml G418 (Gibco/BRL). G418-resistant BHK-21 cell clones were isolated
      and the integrity of hBMP7 gene was determined by PCR using the above PCR
      primers. To package the virus, stably transfected BHK-21 cells were subsequently
      infected with recombinant herpes simplex virus type 1 (rHSV-1). The collected
      cells were processed by chloroform treatment, PEG8000/NaCl precipitation and
      chloroform extraction for purification. The titer was determined using
      quantitative DNA dot blots and the purity was examined by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. Following infection with rAAV2-BMP7 at
      multiplicities of infection of 1 x 10(5) vector genomes per cell and subsequent
      culture, MSCs were assessed qualitatively for BMP7 production. RESULTS: Transient
      transfection showed an efficiency of 98.8% in MSCs. RT-PCR showed that MSCs had
      transcription of BMP7 that was enhanced by the gene transfer. BMP-7 expression in
      MSCs was identified by Western-blot. CONCLUSIONS: The hBMP7 recombinant adeno
      associated virus vector is successfully constructed. The present in vitro study
      demonstrates that rAAV2-BMP7 could infect MSCs.

PMID- 18067755
TI  - Screening for coronary artery disease in asymptomatic patients with type 2
      diabetes mellitus.

PMID- 18067756
TI  - Outcomes after primary coronary intervention with drug-eluting stent implantation
      in diabetic patients with acute ST elevation myocardial infarction.
AB  - BACKGROUND: Drug-eluting stent (DES) has been used widely for the treatment of
      patients with acute coronary syndrome with or without diabetes mellitus during
      percutaneous coronary intervention (PCI), but its long-term safety and efficacy
      in diabetic patients with acute ST elevation myocardial infarction (STEMI) remain
      uncertain. This study aimed to investigate the clinical outcomes after primary
      coronary intervention with DES implantation for diabetic patients with acute
      STEMI, compared with non-diabetic counterparts. METHODS: From December 2004 to
      March 2006, 56 consecutive diabetic patients (diabetic group) and 170 non
      diabetic patients (non-diabetic group) with acute STEMI who underwent primary PCI
      with DES implantation in 3 hospitals were enrolled. Baseline clinical,
      angiographic, and procedural characteristics, as well as occurrence of major
      adverse cardiac event (MACE) including cardiac death, non-fatal recurrent
      myocardial infarction (re-MI) and target vessel revascularization (TVR) during
      hospitalization and one-year clinical follow-up were compared between the two
      groups. RESULTS: Patients in diabetic group were more hyperlipidemic (69.6% and
      51.8%, P = 0.03) and had longer time delay from symptom onset to admission ((364
      +/- 219) minutes and (309 +/- 223) minutes, P = 0.02) than those in non-diabetic
      group. The culprit vessel distribution, reference vessel diameter, and baseline
      TIMI flow grade were similar between the two groups, but multi-vessel disease was
      more common in diabetic than in non-diabetic group (82.1% and 51.2%, P < 0.001).
      Despite similar TIMI flow grades between the two groups after stenting, the
      occurrence of TIMI myocardial perfusion grade (TMPG) = 2 was lower in diabetic
      group (75.0% vs 88.8% in non-diabetic groups, P = 0.02). The MACE rate was
      similar during hospitalization between the two groups (5.4% vs 3.5%, P = 0.72),
      but it was significantly higher in diabetic group (16.1%) during one-year follow
      up, as compared with non-diabetic group (6.5%, P = 0.03). The cumulative one-year
      MACE-free survival rate was significantly lower in diabetic than in non-diabetic
      group (78.6% vs 90.0%, P = 0.02). Angiographic stent thrombosis occurred in 5.4%
      and 1.2% of the patients in diabetic and non-diabetic group, respectively (P =
      0.19). All of these patients experienced non-fatal myocardial infarction.
      CONCLUSIONS: Although the early clinical outcomes were similar in diabetic and
      non-diabetic patients with acute STEMI treated with DES implantation, the
      cumulative MACE-free survival at one-year follow-up was worse in diabetic than in
      non-diabetic patients. More effective diabetes-related managements may further
      improve the clinical outcomes of diabetic cohort suffering STEMI.

PMID- 18067757
TI  - Comparison of in-hospital and long-term outcomes between a Cypher stent and a
      Taxus stent in Chinese diabetic patients with coronary artery disease.
AB  - BACKGROUND: The sirolimus and paclitaxel distribution patterns and tissue
      residence time may be modified in atherosclerotic lesions for patients with
      diabetes, and the biological mechanisms of action for these agents differ
      significantly. Previous clinical trials have yielded discrepant results of major
      adverse cardiac events and restenosis between a sirolimus-eluting stent and a
      paclitaxel-eluting stent in coronary artery disease. Therefore, this study was
      conducted to compare in-hospital and long-term clinical outcomes between patients
      receiving sirolimus-eluting stent (Cypher or Cypher Select stent) and paclitaxel
      eluting stent (Taxus Express stent) after percutaneous intervention (PCI) in
      Chinese patients with diabetes. METHODS: One hundred and sixty-four consecutive
      diabetic patients underwent PCI in Fuwai Hospital from April 2004 to December
      2004. Of them, 101 patients received Cypher or Cypher Select stents (Cypher
      group, 145 stents) and 63 patients received Taxus Express stents (Taxus group,
      129 stents). Repeat coronary angiography was performed at 6-month and clinical
      outcomes were evaluated at 1- and 3-year follow-up. Stent thrombosis was
      classified according to Academic Research Consortium (ARC). RESULTS: The two
      groups did not differ significantly with respect to cardiac death, recurrent
      myocardial infarction (re-MI), target vessel revascularization (TVR) and
      occurrence of major adverse cardiac events (MACE). And the MACE-free cumulative
      survival at 1- and 3-year follow-up and early, late and very late thrombosis
      rates were also similar in the two groups (all P > 0.05). There was a trend
      favoring PES over SES with regard to reducing cardiac death (0 vs 2.0%, P =
      0.524), re-MI (0 vs 2.0%, P = 0.524), the composite of the cardiac death and re
      MI (0 vs 4.0%, P = 0.299) and very late thrombosis (0 vs 3.0%, P = 0.295) between
      1-year and 3-year follow-up. CONCLUSION: The study indicates that PCI with either
      Cypher or Taxus stents is associated with similar efficacy and safety in the
      small population of Chinese diabetic patients during long-term follow-up.

PMID- 18067758
TI  - Relation of hyperglycemia to ST-segment resolution after primary percutaneous
      coronary intervention for acute myocardial infarction.
AB  - BACKGROUND: Hyperglycemia has been shown to be a powerful predictor of poor
      outcome after ST-segment elevation myocardial infarction (STEMI). This study
      aimed to evaluate the effect of admission glucose on microvascular flow after
      successful primary percutaneous coronary intervention (PCI) in patients with
      STEMI. METHODS: Successful primary PCI was performed in 267 patients with STEMI.
      The maximum ST elevation of single electrocardiogram (ECG) lead before and 60
      minutes after PCI was measured, and patients were then divided into 3 groups
      according to the degree of ST-segment resolution (STR): absent (<30%), partial
      (30% to 70%) or complete (> or =70%). RESULTS: Of the 267 patients, 48 (18.0%)
      had absent STR, 137 (51.3%) experienced partial STR, and 82 (30.7%) had complete
      STR. The degree of STR decreased with increasing admission glucose levels
      (P=0.032), and patients with hyperglycemia (serum glucose level > or =11 mmol/L)
      were more likely to have absent STR (P=0.001). Moreover,hyperglycemia was an
      independent predictor of incomplete STR (odds ratio, 1.870; 95% confidence
      interval, 1.038 to 3.371, P=0.037). CONCLUSIONS: Hyperglycemia on admission is
      associated with abnormal coronary microvascular reperfusion in patients with
      STEMI after successful primary PCI, which may contribute, at least in part, to
      the poor outcomes in these patients.

PMID- 18067759
TI  - Association between peroxisome proliferator-activated receptor-gamma coactivator
      1alpha gene polymorphisms and type 2 diabetes in southern Chinese population:
      role of altered interaction with myocyte enhancer factor 2C.
AB  - BACKGROUND: Some single nucleotide polymorphisms (SNPs) in the peroxisome
      proliferator-activated receptor-gamma coactivator (PGC)-1alpha gene have been
      reported to be associated with type 2 diabetes in different populations, and
      studies on Chinese patients yielded controversial results. The objective of this
      case-control study was to explore the relationship between SNPs of PGC-1alpha and
      type 2 diabetes in the southern Chinese population and to determine whether the
      common variants: Gly482Ser and Thr394Thr, in the PGC-1alpha gene have any impacts
      on interaction with myocyte enhancer factor (MEF) 2C. METHODS: The SNPs in all
      exons of the PGC-1alpha gene was investigated in 50 type 2 diabetic patients
      using polymerase chain reaction-single strand conformational polymorphism (PCR
      SSCP) and direct sequencing. Thereafter, 263 type 2 diabetic patients and 282
      healthy controls were genotyped by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). A bacterial two-hybrid system and site-directed
      mutagenesis were used to investigate whether Gly482Ser and Thr394Thr variants in
      the PGC-1alpha gene alter the interaction with MEF2C. RESULTS: Three frequent
      SNPs (Thr394Thr, Gly482Ser and Thr528Thr) were found in exons of the PGC-1alpha
      gene. Only the Gly482Ser variant had a different distribution between diabetic
      patients and healthy subjects, with the 482Ser allele more frequent in patients
      than in controls (40.1% vs 29.3%, P < 0.01). Even in controls, the 482Ser (A)
      carriers were more likely to have higher levels of total cholesterol and low
      density lipoprotein cholesterol than the 482Gly (G) carriers. The 394A-482G-528A
      haplotype was associated with protection from diabetes, while the 394A-482A-528A
      was associated with the susceptibility to diabetes. The bacterial two-hybrid
      system and site-directed mutagenesis revealed that the 482Ser variant was less
      efficient than the 482Gly variant to interact with MEF2C, whereas the 394Thr (A)
      had a synergic effect on the interaction between 482Ser variant and MEF2C.
      CONCLUSIONS: The results suggested that the 482Ser variant of PGC-1alpha
      conferred the susceptibility to type 2 diabetes in the southern Chinese
      population. The underlying mechanism may be attributable, at least in part, to
      the altered interaction between the different variants (Gly482Ser, Thr394Thr) in
      the PGC-1alpha gene and MEF2C.

PMID- 18067760
TI  - Effect of angiotensin II receptor blocker on glucose-induced mRNA expressions of
      matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat
      mesangial cells.
AB  - BACKGROUND: The decreased degradation of extra-cellular matrix proteins plays an
      important role in the onset of diabetic nephropathy. Matrix metalloproteinase-9
      (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), which are members
      of the matrix metalloproteinase family, are associated with this process.
      Angiotensin II (AII) plays an important role in the development of diabetic
      nephropathy also. This research aimed to investigate the effect of angiotensin II
      receptor blocker on glucose-induced mRNA expressions of MMP-9 and TIMP-1 in rat
      mesangial cells. METHODS: Rat mesangial cells were cultured and divided into 5
      groups: normal glucose (group NG), high glucose (group HG), group NG + AII, NG +
      AII + saralasin (group NG + AII + S, saralasin is the AII receptor blocker) and
      HG + saralasin (group HG + S). After the cells were incubated for 24 hours, AII
      concentrations in the supernatant were measured by radioimmunoassay and the
      expression of MMP-9 and TIMP-1 mRNA was assayed by reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: AII concentrations were higher in
      group HG ((56.90 +/- 13.54) pg/ml) and group HG + S ((51.30 +/- 5.96) pg/ml) than
      in group NG ((37.89 +/- 8.62) pg/ml, P < 0.05), whereas there was no significant
      difference between group HG and group HG + S. The expression of MMP-9 mRNA and
      MMP-9/TIMP-1 mRNA ratio in group NG + AII (MMP-9, 0.33 +/- 0.04; MMP-9/TIMP-1,
      0.40 +/- 0.06) and group HG (MMP-9, 0.36 +/- 0.02; MMP-9/TIMP-1, 0.45 +/- 0.03)
      were decreased more significantly than those in group NG (MMP-9, 0.72 +/- 0.02;
      MMP-9/TIMP-1, 1.21 +/- 0.07). These values in group NG + AII + S (MMP-9, 0.71 +/-
      0.02; MMP-9/TIMP-1, 1.18 +/- 0.05) were higher than those in group NG + AII, and
      the values in group HG + S (MMP-9, 0.71 +/- 0.02; MMP-9/TIMP-1, 1.16 +/- 0.05)
      were higher than those in group HG (all were P < 0.05). TIMP-1 mRNA expression
      was increased more significantly in group NG + AII (0.81 +/- 0.03) and group HG
      (0.80 +/- 0.03) than in group NG (0.59 +/- 0.02), but it was lower in group NG +
      AII + S (0.60 +/- 0.01) than in group NG + AII and also lower in group HG + S
      (0.61 +/- 0.01) than in group HG (all were P < 0.05). CONCLUSIONS: High glucose
      stimulates AII production. Both high glucose and AII induce a decrease in MMP-9
      mRNA expression and MMP-9/TIMP-1 mRNA ratio as well as an increase in TIMP-1 mRNA
      expression, which can be reversed by saralasin, suggesting that high glucose can
      aggravate impaired matrix degradation by altering gene expression of MMP-9 and
      TIMP-1 and that the effect of high glucose may be mediated by AII.

PMID- 18067761
TI  - Real-time myocardial contrast echocardiography can predict functional recovery
      and left ventricular remodeling after revascularization in patients with ischemic
      heart disease.
AB  - BACKGROUND: Previous studies showed that preservation of microvascular integrity
      after myocardial ischemia was associated with myocardial viability. Real-time
      myocardial contrast echocardiography (RT-MCE) is a promising modality for non
      invasive evaluation of microcirculation perfusion. Thus, it provides a unique
      tool to detect myocardial viability. We sought in this study to investigate the
      role of RT-MCE in predicting left ventricular (LV) functional recovery and
      remodeling after revascularization in patients with ischemic heart disease.
      METHODS: Thirty-one patients with ischemic heart disease and resting regional LV
      dysfunction were included. LV volume, global and regional function were evaluated
      by echocardiography before and 6 - 9 months after revascularization. RT-MCE was
      performed before revascularization using low mechanical index power modulation
      imaging. Myocardial contrast opacification of dysfunctional segments was scored
      on a 3-point scale and mean contrast score in dysfunctional segments was
      calculated. Patients were divided into 2 groups according to mean contrast score
      in dysfunctional segments: group A, patients with mean contrast score = 0.5 (n =
      19); group B, patients with mean contrast score < 0.5 (n = 12). RESULTS: Wall
      motion improvement was found to be 94.5%, 45.5% and 16.1% respectively (P < 0.01)
      in homogenous, patchy and absent contrast opacification segments. At baseline,
      there was no significant difference in LV volume and global function between the
      two groups. After revascularization, group B had significantly larger LV end
      diastolic volume (LVEDV) and LV end-systolic volume (LVESV), lower LV ejection
      fraction (LVEF) and higher wall motion score index (WMSI) than those of group A
      (all P < 0.05). Revascularization was followed by significant improvement of LV
      volume and recovery of global LV function in group A (all P < 0.01); however, in
      group B, after revascularization, deterioration of LVEDV (P < 0.05) was observed,
      moreover LVESV, WMSI and LVEF did not change significantly. CONCLUSIONS: The
      maintenance of myocardial microcirculation detected by RT-MCE can predict
      functional recovery and LV remodeling after revascularization in patients with
      ischemic heart disease, which might be helpful in clinical decision-making and
      risk stratification.

PMID- 18067762
TI  - Characteristics of myocardial postsystolic shortening in patients with coronary
      artery disease assessed by strain rate imaging.
AB  - BACKGROUND: Postsystolic shortening (PSS) has been proposed as a marker of
      myocardial dysfunction. Strain rate imaging (SRI) is a novel ultrasonic
      technique, allowing reliable and noninvasive measurement of myocardial
      deformation. The purpose of this study was to investigate the characteristics of
      myocardial longitudinal PSS by SRI in ischemic and infarct myocardium in patients
      with coronary artery disease, and to explore its clinical applicability. METHODS:
      Eleven patients with angina pectoris, 21 patients with myocardial infarction and
      20 healthy subjects were included in the study. Apical four-, three- and two
      chamber views were displayed; and septal, lateral, anteroseptal, posterior,
      anterior and inferior walls of the left ventricle were scanned, respectively. PSS
      strain (epsilon(pss)), the ratio of epsilon(pss) and systolic strain
      (epsilon(pss)/epsilon(sys)), the ratio of epsilon(pss) and maximum strain
      (epsilon(pss)/epsilon(max)) and the duration of PSS (T(pss)) in ischemic, infarct
      and normal myocardium were analyzed. RESULTS: PSS was found more frequent in the
      ischemic and infarct segments compared with the normal segments (39% vs 22% and
      56% vs 22%, respectively; both P < 0.01). It was even more frequent in the
      infarct segments than in the ischemic segments (56% vs 39%, P < 0.01). The
      absolute magnitude of epsilon(pss), epsilon(pss)/epsilon(sys),
      epsilon(pss)/epsilon(max) were significantly larger and T(pss) significantly
      longer in the ischemic and infarct segments compared with that in the normal
      myocardium (P < 0.01). epsilon(pss)/epsilon(sys), epsilon(pss)/epsilon(max) were
      even larger and T(pss) even longer in the infarct than in the ischemic segments
      (P < 0.01). CONCLUSIONS: PSS is a common and important feature of the ischemic
      and infarct myocardium. epsilon(pss), epsilon(pss)/epsilon(sys),
      epsilon(pss)/epsilon(max) and T(pss) as measured by SRI may be promising markers
      for the quantitative assessment of regional myocardial dysfunction in patients
      with coronary artery disease. epsilon(pss)/epsilon(sys),
      epsilon(pss)/epsilon(max) and T(pss) may be helpful in differentiating infarct
      from ischemic myocardium.

PMID- 18067763
TI  - Interventricular septum motion abnormalities: unexpected echocardiographic
      changes of Brugada syndrome.
AB  - BACKGROUND: There remains controversy about whether Brugada syndrome (BS) has
      structural heart changes. We occasionally noted that a patient with BS had a
      quite unusual regional wall motion abnormality at the basal segment of the
      interventricular septum (IVS) during echocardiographic examination. The
      unexpected finding promoted us to reexamine our patients with BS by
      echocardiographic interrogation in the present study. METHODS: Patients with BS
      (n = 11), patients with complete right bundle branch block (RBBB) (n = 11), and
      control subjects (n = 11) were enrolled in this study. Two-dimensional
      echocardiography (2DE) was performed to obtain parasternal left ventricular long
      axis view on which M-mode scanning line was adjusted to be perpendicular to the
      basal segment of IVS for delineation of the segmental motion curve, with a
      simultaneously electrocardiographic tracing. RESULTS: 2DE revealed a rapid swing
      motion shifting toward the right ventricle of the IVS basal segment at early
      systole in 73% (8/11) patients with BS, which was further confirmed on the M-mode
      curve evidenced by an early systolic notch toward the right ventricle. The
      position of the notch corresponded to C-point on the mitral motion curve, lasting
      for (53 +/- 5) ms. There were no similar changes both in patients with RBBB and
      in the control subjects. CONCLUSION: IVS basal motion abnormalities at early
      systolic phase may be the novel finding of BS.

PMID- 18067764
TI  - Atorvastatin prevents connexin43 remodeling in hypertrophied left ventricular
      myocardium of spontaneously hypertensive rats.
AB  - BACKGROUND: Connexin43 (Cx43) is the predominant gap junction protein in heart
      and is involved in the control of cell-to-cell communication to modulate the
      contractility and the electrical coupling of cardiac myocytes. Left ventricular
      (LV) hypertrophy is accompanied by changes of Cx43 expression. Recent studies
      have demonstrated that statins reduced cardiac hypertrophy. However, it is
      unknown whether statins can affect Cx43 expression in hypertrophied left
      ventricular myocardium. This study was designed to assess the effects of
      atorvastatin on LV hypertrophy and Cx43 expression in spontaneously hypertensive
      rats (SHR). METHODS: Nine-week old SHRs were randomly divided into two groups.
      Some received atorvastatin at 30 mg/kg by oral gavage once daily for 8 weeks (SHR
      A); others received vehicle. Age-matched Wistar-Kyoto rats (WKY) received
      atorvastatin or vehicle for 8 weeks were used as controls. At the end of the
      experiment, we investigated LV hypertrophy and the expression of Cx43 in LV
      myocardium in four groups. Cx43 expression was investigated by the methods of
      Western blotting, immunohistochemistry, and transmission electron microscope. LV
      hypertrophy was accessed by pathological analysis and plasma brain natriuretic
      peptide (BNP) level. RESULTS: LV hypertrophy was prominent in untreated SHR. In
      SHR, LV myocardium Cx43 level was upregulated, and the distribution of Cx43 was
      displaced from their usual locations to other sites at various distances away
      from the intercalated disks. After atorvastatin treatment, myocardium Cx43 level
      was reduced in SHR-A, and the distribution of Cx43 gap junction became much
      regular and confined to intercalated disk. Statins also prevented LV hypertrophy
      in SHR. CONCLUSIONS: These results provide novel in vivo evidence for the key
      role of Cx43 gap junctions in LV hypertrophy and the possible mechanism in anti
      hypertrophic effect of statins. Atorvastatin treatment may have beneficial
      effects on LV hypertrophy in spontaneously hypertensive rats.

PMID- 18067765
TI  - Identification of a detailed function list for public health emergency management
      using three qualitative methods.
AB  - BACKGROUND: At present, many administrators lack a theoretical guide to build
      management systems to cope with public health emergencies. This study developed a
      detailed function list for public health emergency management to help building
      the management systems scientifically. METHODS: The five steps in this study
      including literature review, semistructured interviews with experts, focus group,
      Delphi study and focus group were conducted to develop the detailed list of
      functions. RESULTS: An initial list of 25 functions with 188 items was formed
      through literature review. The list was reduced to 10 functions with 57 items by
      semistructured interviews with experts and focus group. Next, all these 57 items
      reached the consensus through one-round Delphi study. Some revisions of the
      consensus were done by the same focus group. CONCLUSION: The final 10 functions
      with 57 items could be used as a guide for most countries during their building
      of a public health emergency management system.

PMID- 18067766
TI  - Angiographic differentiation of systolic narrowing of the left anterior
      descending coronary artery in hypertrophic cardiomyopathy from myocardial
      bridges.

PMID- 18067767
TI  - Surgical techniques of arterialized orthotopic liver transplantation in rats.
AB  - BACKGROUND: Recently, much attention has been paid to hepatic artery
      reconstruction in rat liver transplantation, which can prevent bile duct ischemia
      and preserve better liver structure. In this study, three methods of graft
      arterialization, including sleeve, cuff, and stent anastomosis, were conducted
      and the results were compared. METHODS: Orthotopic liver transplantation (OLT)
      with rearterialization was conducted in 90 rats, which were divided into sleeve,
      cuff, and stent groups (n = 30 in each). Ninety-six rats received OLTs with
      standardized two-cuff technique without rearterialization as a control. The
      sleeve technique included an end-to-end anastomosis between the donor common
      hepatic artery and recipient proper hepatic artery, or between the donor celiac
      artery and recipient common hepatic artery. Cuff technique involved an
      anastomosis between the donor common hepatic artery and recipient common hepatic
      artery. In the stent technique, the recipient hepatic artery and donor hepatic
      artery were connected using an intraluminal polyethylene stent. The arterial
      anastomosis time and arterial patency rate in each group were recorded. The liver
      graft survival and bile duct complication rates were measured. RESULTS: The total
      surgical time of OLT with rearterialization was (118.3 +/- 12.9) minutes in the
      sleeve group, (106.2 +/- 11.6) minutes in the cuff, (93.8 +/- 10.2) minutes in
      the stent, and (88.2 +/- 9.6) minutes in the control. The corresponding anhepatic
      phase was (19.6 +/- 2.8), (19.2 +/- 2.2), (18.6 +/- 1.8), and (20.0 +/- 2.5)
      minutes respectively in the sleeve, cuff, stent, and control groups. One-week
      survival rate was 86.5% in the control, and 86.7% in the groups with
      rearterialization. No significant difference was detected in the survival rate
      between them (P > 0.05). The incidence of biliary complications in non
      rearterialized group (17.7%) was significantly higher than that in the
      rearterialized group (6.7%, P < 0.05). No significant difference was found in the
      incidence of biliary complications among the three rearterialized groups (P >
      0.05). CONCLUSIONS: The OLT with rearterialization is more physiological than
      that without rearterialization, and leads to a lower rate of bile duct
      complications. Among the three methods of rearterialization, sleeve anastomosis
      is associated with a higher survival rate, allowing less dissection and less
      injury to the surrounding tissues.

PMID- 18067768
TI  - Inflammation markers as mediators of vasculo-endothelial dysfunction and
      atherosclerosis in the metabolic syndrome.

PMID- 18067769
TI  - Epithelial to mesenchymal transition in the progression of tubulointerstitial
      fibrosis.
AB  - OBJECTIVE: To review the mechanisms of epithelial to mesenchymal transition (EMT)
      and its role in the progression of tubulointerstitial fibrosis. DATA SOURCES: The
      data used in this review were obtained mainly from the studies of EMT reported
      from 2000-2006. STUDY SELECTION: Relevant articles on studies of EMT in
      tubulointerstitial fibrosis were selected. Data were mainly extracted from the 45
      articles listed in the reference section of this review. RESULTS: The process of
      EMT has gained wide recognition as candidate mechanism in progression of chronic
      fibrotic disorders. New markers were identified and facilitate the observation of
      EMT. EMT is regulated by many factors through activation of kinase-dependent
      signaling cascades. Recent findings suggest that EMT is a reversible process,
      which can be controlled by factors for their epithelial inducing activities.
      CONCLUSION: Remarkable progresses of EMT research have been made recently.
      Preventing or reversing EMT is a promising strategy against renal fibrosis.

PMID- 18067770
TI  - Screening for a human single chain Fv antibody against epitope on amyloid-beta 1
      40 from a human phage display library.

PMID- 18067771
TI  - Endoscopic ultrasonography and submucosal resection in the diagnosis and
      treatment of rectal carcinoid tumors.

PMID- 18067772
TI  - Bilateral nontuberculous mycobacterial keratitis after laser in situ
      keratomileusis.

PMID- 18067773
TI  - Postcardiac injury syndrome complicating circumferential pulmonary vein
      radiofrequency ablation for atrial fibrillation.

PMID- 18067774
TI  - Balloon catheterization for hemostasis during the operation of ruptured femoral
      artery pseudoaneurysm.

PMID- 18067775
TI  - Circadian rhythm: a new clue for neuropsychological dysfunction after cardiac
      surgery.

PMID- 18067776
TI  - Mechanisms of postoperative pain.

PMID- 18067777
TI  - Postoperative neuropsychological change and its underlying mechanism in patients
      undergoing coronary artery bypass grafting.
AB  - BACKGROUND: The high incidence of neuropsychologic deficits after cardiac
      surgery, including cognitive dysfunction and mood status, has significantly
      influenced the prognosis, outcome of treatment and long-term quality of life of
      patients. With a circadian secretion pattern, melatonin and cortisol are capable
      of modulating the human physiological processes and neuropsychological status,
      whereas disorder of their secretion pattern may lead to many diseases. However,
      it is unclear whether neuroendocrine variations are related to the
      neuropsychologic status in patients undergoing coronary artery bypass grafting
      (CABG). METHODS: Forty male patients scheduled for CABG with hypothermic
      cardiopulmonary bypass (CPB) (n = 20) or off-pump coronary artery bypass (OPCAB)
      (n = 20) were studied. Blood samples were taken intraoperatively at specific time
      points and every 3 hours within the first postoperative 24 hours to determine
      plasma concentrations of melatonin and cortisol. A neuropsychologic test battery
      including depression and anxiety was administered preoperatively and 7 to 10 days
      postoperatively. Statistical methods included the nonparametric analysis,
      multiple linear regression and cosinor analysis. RESULTS: The patients in the CPB
      group exhibited more severe neuropsychologic deficits and more anxious than those
      in the OPCAB group after surgery. In both groups, patients were more depressed
      postoperatively than preoperatively and recovered 3 months after surgery.
      Depression and anxiety were correlated with some factors of cognitive
      dysfunctions. In the postoperative 24 hours, 2 patients in the CPB group, and 6
      patients in the OPCAB group showed a circadian rhythm of melatonin secretion. As
      for cortisol secretion, there were 3 patients in the CPB group and 7 in the OPCAB
      group respectively. Parameters of circadian rhythm of melatonin in the CPB group
      and those of secretion rhythm of cortisol in both groups were correlated with
      depression and some neuropsychologic tests. CONCLUSIONS: The incidence of
      neuropsychological deficits was higher in patients receiving CABG with CPB than
      in those without CPB. The status of mood may contribute to the perioperative
      cognitive dysfunctions. The disordered circadian rhythm of melatonin secretion in
      patients undergoing CABG with CPB and the disordered cortisol secretion may
      correlate directly or indirectly through mood with neuropsychological deficits.

PMID- 18067778
TI  - Shenfu injection attenuates neurotoxicity of bupivacaine in cultured mouse spinal
      cord neurons.
AB  - BACKGROUND: Our previous in vivo study in the rat demonstrates that Shenfu
      injection, a clinically used extract preparation from Chinese herbs, attenuates
      neural and cardiac toxicity induced by intravenous infusion of bupivacaine, a
      local anesthetic. This study was designed to investigate whether bupivacaine
      could induce a toxic effect in primary cultured mouse spinal cord neuron and if
      so, whether the Shenfu injection had a similar neuroprotective effect in the cell
      model. METHODS: The spinal cords from 11- to 14-day-old fetal mice were minced
      and incubated. Cytarabine was added into the medium to inhibit the proliferation
      of non-neuronal cells. The immunocytochemical staining of beta-tubulin was used
      to determine the identity of cultured cells. The cultured neurons were randomly
      assigned into three sets treated with various doses of bupivacaine, Shenfu and
      bupivacaine + Shenfu, for 48 hours respectively. Cell viability in each group was
      analyzed by methyl thiazoleterazolium (MTT) assay. RESULTS: The viability of the
      cultured neurons treated with bupivacaine at concentrations of 0.01%, 0.02%,
      0.04% and 0.08% was decreased in a dose-dependent manner. Although the Shenfu
      injection at concentrations ranging from 1/50 to 1/12.5 (V/V) had no significant
      influence on the viability of cultured neurons (P < 0.05 vs control), the
      injection significantly increased the cellular viability of cultured neurons
      pretreated with 0.03% bupivacaine (P < 0.05). CONCLUSION: Although Shenfu
      injection itself has no effect on spinal neurons, it was able to reduce the
      bupivacaine-induced neurotoxicity in vitro.

PMID- 18067779
TI  - Fluids administration and coagulation characteristics in patients with different
      model for end-stage liver disease scores undergoing orthotopic liver
      transplantation.
AB  - BACKGROUND: There have been many studies investigating the impact of the model
      for end-stage liver disease (MELD) score on predicting post-transplant outcome.
      But it is unclear whether MELD is correlated to intraoperative fluid therapy and
      coagulation status. We investigated the relationship between the severity of
      liver diseases as measured by MELD score and intraoperative fluid requirements
      and the changes of coagulation characteristics. METHODS: Ninety patients were
      included in this retrospective study. The patients were stratified into three
      groups according to the MELD scores: < 15 (low), 15 - 25 (medium) and > 25
      (high). Intraoperatively, volume was restored with allogeneic and/or salvaged red
      blood cells (RBC), fresh-frozen plasma (FFP), platelet and other types of fluids
      according to hemodynamic data, hematocrit, and clotting data. Intraoperative
      coagulation data, blood requirements and other fluids administered were compared
      among the 3 groups. RESULTS: Before surgery, in addition to the three variables
      used to calculate MELD scores in other baseline laboratory values, including
      ratio of activated partial thromboplastin time (R-APTT), D-Dimer, hematocrit,
      platelet and blood urea nitrogen (BUN) were significantly different among the 3
      groups. The blood loss increased with increasing MELD. The volume of RBC
      (allogeneinc, salvaged and total), FFP, platelet and the total volume of
      transfusion were also significantly different among the three groups (P < 0.01).
      The requirements for prothrombin complex and fibrinogen showed a similar pattern.
      During operation, the changing trends of each coagulation variable were
      different. Compared with baseline, during each intraoperative stage, INR and R
      APPT increased in the low MELD group. While in the medium MELD and high MELD
      groups, INR did not changed significantly during the operation, and R-APPT
      significantly increased only after reperfusion. CONCLUSIONS: This study provided
      some useful information for perioperative management of patients undergoing liver
      transplantation. Careful preoperative planning and resource preparation are
      crucial for patients with high MELD scores. Close communication between surgeon,
      anesthesiologist and the transfusion staff of blood bank before and during
      surgery should be stressed.

PMID- 18067780
TI  - Spinal release of the amino acids with a time course in a rat model of
      postoperative pain.
AB  - BACKGROUND: The mechanisms underlying postoperative pain remain unclear.
      Neurotransmitters of excitatory and inhibitory amino acids play an important role
      in the transmission and modulation of pain in the spinal dorsal horn. This study
      aimed to investigate the changes of release of excitatory and inhibitory amino
      acids in the spinal cord during postoperative pain and to provide a novel
      theoretical basis for postoperative pain management. METHODS: Loop microdialysis
      catheters were implanted subarachnoidally via the atlanto-occipital membrane in
      16 healthy Sprague-Dawley rats. All rats without neural deficits were divided
      into two groups, Group A and Group B, following 5 days of recovery. The tubes for
      microdialysis were connected and 25 microl microdialysate sample for baseline
      value was collected after one-hour washout in each rat. A plantar incision in the
      right hind paws of rats in Group A were performed under 1.2% isoflurane. All rats
      in Group B were only anesthetized by 1.2% isoflurane for the same duration. The
      microdialysate samples were collected at 3 hours, 1 day, 2 days and 3 days after
      the incision (or isoflurane anesthesia in Group B) in both groups. The cumulative
      pain scores were also assessed at the above time-points. The amino acids in the
      microdialysate samples were tested using high performance liquid chromatography.
      RESULTS: Within Group A, the release of aspartate and glutamate at 3 hours after
      the incision was significantly higher than the baseline values and the release of
      glycine at 1 day after the incision significantly increased compared with the
      baseline values (P < 0.01). Within Group B, the release of neurotransmitters at
      each time point had no significant difference compared with the baseline values
      (P > 0.05). The release of aspartate and glutamate at 3 hours after the incision
      in Group A was significantly higher than that in Group B (P < 0.01). The release
      of glycine at 1 day after the incision in Group A significantly increased
      compared with Group B (P < 0.01). The cumulative pain scores at 3 hours, 1 day
      and 2 days after the incision in Group A were significantly higher than those in
      Group B (P < 0.01). CONCLUSIONS: The release of the excitatory amino acids occurs
      in the early phase of postoperative pain and might not be involved in the
      maintenance of pain in a rat model of incision pain. The release of inhibitory
      glycine lagged behind the excitatory amino acids. The implication of inhibitory
      glycine release remained to be established further.

PMID- 18067781
TI  - Synergistic myoprotection of L-arginine and adenosine in a canine model of global
      myocardial ischaemic reperfusion injury.
AB  - BACKGROUND: Endogenous nitric oxide and adenosine increase simultaneously to keep
      the balance of energy demand and supply when the oxygen supply is insufficient,
      which suggests that nitric oxide and adenosine might exert a synergistic
      myoprotection during tissue hypoxia. In this study, we tested this hypothesis
      utilizing a canine model of prolonged global myocardial ischaemic reperfusion
      injury. METHODS: In this double blind, controlled study, the hearts of 24
      anaesthetized mongrel dogs were arrested for 2 hours with aortic cross clamping
      and blood cardioplegia. The treatment groups were those supplemented with 2
      mmol/L L-arginine (ARG), supplemented with 1 mmol/L adenosine (ADO), ARG + ADO
      supplemented with both, and no supplementation (control) (n = 6 in each group).
      Haemodynamics, biochemical indices, adenosine triphosphate (ATP) content and
      myeloperoxidase activities of myocardium were determined to evaluate myocardial
      injury. Statistical comparison was performed by two way ANOVA. RESULTS: Although
      the requirements for inotropic supports were higher, the cardiac outputs were
      lower in control group than in ARG, ADO and the combination groups. Plasma
      cardiac troponin I levels were higher and the areas of hydropic changes were
      larger in control group than in ARG and ADO groups. Combination of arginine and
      adenosine provided further myoprotection with respect to better cardiac
      performance, lower release of cardiac troponin I, and smaller areas of hydropic
      changes compared with ARG and ADO groups. ATP content was higher, but
      myeloperoxidase activities of myocardium were significantly lower in the
      combination group than in control, ARG and ADO groups (P < 0.05). CONCLUSIONS:
      Combination of L-arginine and adenosine provides synergistic myoprotection in a
      canine model of global myocardial ischaemia. Thus, the combination is recommended
      when the heart is exposed to a prolonged ischaemia during cardiac surgery.

PMID- 18067782
TI  - Single-center report of 5-year follow-up on 94 patients underwent transmyocardial
      laser revascularization.
AB  - BACKGROUND: Transmyocardial laser revascularization (TMLR) has been used in the
      treatment of patients with end-stage coronary artery disease (CAD) since 1990.
      The aim of this study was to evaluate the long-term effectiveness of TMLR in
      patients with diffuse CAD. METHODS: Ninety-four consecutive patients underwent
      TMLR in one center from July 1997 to December 2000. The follow-up data of these
      patients were obtained through face-to-face, mail questionnaires, or telephone
      interviews in July 2004 and December 2004. Four cases failed to respond. Mean
      follow-up time was (5.5 +/- 1.0) years. RESULTS: Mean Canadian Cardiovascular
      Society (CCS) angina scores of TMLR patients were 3.1 +/- 0.8 at baseline, 1.7 +/
      0.9 at 1 year (P < 0.05), 1.7 +/- 0.9 at 3 years (P < 0.05), and 1.9 +/- 0.9 at
      5 years (P < 0.05). At an average of 5 years, 69% of the patients had > or = 1
      angina class reduction, mean NYHA class level (1.9 +/- 0.9) ameliorated compared
      to the baseline (2.5 +/- 0.7, P < 0.001), the rate of re-hospitalization was 2.7
      times/person. Kaplan-Meier survival rate was 87% at 1 year, 69% at 3 years and
      64% at 5 years. The causes of death were attributed more to heart failure (58.9%)
      and myocardial infraction (14.7%) after TMLR. The patients with no angina relief,
      or who died after TMLR, had a higher percentage of preoperative unstable anginas
      or prior myocardial infraction compared to the survivors. The assorted shapes of
      myocardial laser channels were detected in some patients by the color Doppler
      velocity technique. CONCLUSIONS: TMLR provided a long-term improvement in the
      quality of life, including CCS angina class or NYHA heart functional class for
      about 70% of Chinese patients with severely disabling angina pectoris. The
      various myocardial laser channels would always be visible after TMLR. 5-years
      after TMLR as a sole therapy, the survival rate of the patients was 64%.

PMID- 18067783
TI  - Early local intracoronary platelet activation after drug-eluting stent placement.
AB  - BACKGROUND: Early local platelet activation after coronary intervention
      identifies patients at increased risk of acute stent thrombosis (AST). However,
      early changes in platelet activation in coronary circulation following drug
      eluting stent (DES) implantation have never been reported. METHODS: In a
      prospective study of 26 consecutive elective stable angina patients, platelet
      activation was analyzed by measuring soluble glycoprotein V (sGPV) and P-selectin
      (CD62P) before and after implantation of either DES or bare metal stent (BMS).
      All patients were pretreated with clopidogrel (300 mg loading dose) and aspirin
      (75 mg orally) the day before the procedure. Blood samples were drawn from the
      coronary ostium and 10 - 20 mm distal to the lesion site. RESULTS: Consistent
      with the lower baseline clinical risk, the levels of CD62P and sGPV were within
      normal reference range, both in the coronary ostium and distal to the lesion
      before percutaneous coronary intervention (PCI) procedure. The levels of CD62P
      and sGPV did not change significantly (CD62P: (31.1 +/- 9.86) ng/ml vs (29.5 +/-
      9.02) ng/ml, P = 0.319 and sGPV: (52.4 +/- 13.5) ng/ml vs (51.8 +/- 11.7) ng/ml,
      P = 0.674, respectively) after stent implantation when compared with baseline.
      Changes in these platelet activation markers did not differ between stent types.
      CONCLUSIONS: Intracoronary local platelet activation does not occur in stable
      angina patients before and immediately following DES implantation when dual anti
      platelet is administered.

PMID- 18067784
TI  - In vitro anti-inflammatory effects of different solution fractions of ethanol
      extract from Melilotus suaveolens Ledeb.
AB  - BACKGROUND: Melilotus suaveolens Ledeb (M. suaveolens Ledeb) has long been used
      as a folk medicine in inflammation-related therapy. This study was undertaken to
      determine the anti-inflammatory effect of the plant. METHODS: Petroleum ether
      fraction, ethyl acetate fraction, n-butanol fraction, aqueous fraction were
      obtained from ethanol extract of M. suaveolens Ledeb and evaluated by high
      performance liquid chromatography (HPLC). While dexamethasone (DM) was used as a
      positive control, the effects of different solution fractions of ethanol extract
      on tumor necrosis factor alpha (TNF-alpha) mRNA, cyclooxygenase 2 (COX-2) mRNA,
      COX-2 and nuclear factor kappaB (NF-kappaB) of LPS-stimulated RAW 264.7 cells
      were studied by real-time PCR, Western blot analysis and immunocytochemical
      assay, respectively. RESULTS: Coumarin was one of the main ingredients in
      different solution fractions of ethanol extract except the aqueous fraction with
      no inflammatory effect. The petroleum ether fraction, ethyl acetate fraction and
      n-butanol fraction of ethanol extract could inhibit the production of TNF-alpha
      mRNA, COX-2 mRNA and NF-kappaB to some extent. CONCLUSIONS: Different solution
      fractions of ethanol extract from M. suaveolens Ledeb had similar anti
      inflammatory effect as did dexamethasone except the aqueous fraction. Coumarin
      was likely to be essential to the anti-inflammatory effect, and other ingredients
      might attribute to their different anti-inflammatory effects from the HPLC
      fingerprint.

PMID- 18067785
TI  - Oncosis in human esophageal squamous cell carcinoma and its relationship with
      apoptosis and microvessel density.
AB  - BACKGROUND: Previous studies have shown that oncosis in malignant tumors might be
      related to cellular energy supply. The aim of this study was to detect oncosis in
      human esophageal squamous cell carcinoma (ESCC), and to investigate its
      relationship with apoptosis and microvessel density (MVD). METHODS: ESCC
      specimens were obtained from 30 patients with ESCC after surgery. Transmission
      electron microscopy, TUNEL, and immunohistochemistry were used to detect oncosis,
      apoptosis, and MVD. The relation of oncosis to apoptosis and MVD was analyzed by
      ANOVA, t test, and q test using SPSS 10.0. RESULTS: Transmission electron
      microscopy revealed both oncosis and apoptosis in the ECSS tissues. About 10% of
      the TUNEL-positive cells, which were considered apoptotic cells, showed the
      characteristics of oncosis. In the areas, where oncotic cells accumulated,
      apoptotic cells were rare; contrarily, where apoptotic cells gathered, oncotic
      cells were sparse. Compared with the tissues with a high MVD, the number of
      oncotic cells was increased and that of apoptotic cells was decreased in the
      tissues with a low MVD. CONCLUSIONS: Cellular oncosis can be detected in human
      ESCC tissues. The distribution of oncotic cells presents a close relationship
      with cellular apoptosis and MVD. Oncosis might be induced by poor blood supply.

PMID- 18067786
TI  - Molecular genetic evidence of Y chromosome loss in male patients with
      hematological disorders.
AB  - BACKGROUND: There has been continuous debate as to whether Y chromosome loss is
      an age related phenomenon or a cytogenetic marker indicating a malignant change.
      This study aimed to investigate the frequency of Y chromosome loss in the
      specific patients in order to determine whether it is an age related phenomena or
      a cytogenetic marker indicating a malignant change. METHODS: Five hundred and
      ninety-two male patients with a median age of 59 years old (22 - 95 years) were
      included in this study. These patients were divided into two groups: the study
      group, including 237 patients who had hematological disorders included
      myeloproliferative disorder (MPD), myelodysplastic syndrome (MDS), acute myeloid
      leukemia (AML), chronic myeloid leukemia (CML), multiple myeloma (MM), and
      lymphoma and the control group including 355 patients with no evidence of
      hematological disease. Both conventional cytogenetics and fluorescence in situ
      hybridization using DNA probes specific for the centromere of chromosomes X or Y
      were performed according to our standard laboratory protocols. RESULTS: Twenty
      four out of 237 patients with hematological disorders (10.1%) had Y chromosome
      loss. Of these 24 patients, 2 patients had AML (5.0% of all AML patients), 2
      patients had CML (5.7% of all CML patients), 2 patients had MPD (8.0% of all MPD
      patients), 3 patients had MM (10.0% of all MM patients), 5 patients had lymphoma
      (10.6% of all lymphoma patients) and 10 patients had MDS (16.7% of all MDS
      patients). Twenty-one out of these 24 patients had a loss of Y chromosome as the
      sole anomaly and the remaining three had a loss of Y chromosome accompanied with
      other structural changes detected by conventional cytogenetic analysis.
      Fluorescence in situ hybridization (FISH) analysis confirmed the routine
      cytogenetic results. All 24 patients had a loss of Y chromosome with a range of
      17.5% - 98.5% of cells. Two of the patients, one with AML and another with CML,
      had karyotype and FISH testing done both at the initial diagnosis and during
      remission. The results showed a loss of Y chromosome at initial diagnosis but a
      normal 46, XY karyotype during remission. Only 9 out of 355 patients (2.5%)
      without evidence of hematological disease had Y chromosome loss, among them 7
      patients had cardiovascular diseases and 2 patients had kidney diseases.
      Comparison of the incidence of Y chromosome loss in patients with hematological
      disorders or without evidence of hematological disease using statistical analysis
      showed a statistically significance difference (P < 0.05). CONCLUSIONS: The
      present study demonstrated that the frequency of Y chromosome loss is
      significantly higher in patients with hematological disorders than in patients
      without hematological disorders, which indicates that the loss of Y chromosome is
      associated with a neoplastic change.

PMID- 18067787
TI  - Subtype and sequence analysis of HIV-1 strains in Heilongjiang Province.
AB  - BACKGROUND: Human immunodeficiency virus (HIV-1) is divided into two types, HIV-1
      (groups M, N and O) and HIV-2. Heilongjiang Province located in the northeast of
      China, and the feature of the subtype distribution and sequence characteristics
      of HIV-1 strains prevalent in Heilongjiang Province is still uncertain. The aim
      of this study was to investigate the subtype distribution and genetic
      characteristics of HIV-1 strains in one hospital in Heilongjiang Province.
      METHODS: HIV-1 env gene was amplified by nested-PCR from peripheral blood
      mononuclear cells (PBMCs) obtained from 19 HIV-1 seropositive individuals in
      Heilongjiang Province. The C2-V3 region was sequenced. Aligned the nucleotide
      sequence of 19 samples with CLUSTAL W (BioEdit) software, results were acquired
      and used for phylogenetic tree analysis after artificial adjustment. Reference
      sequence, downloaded from Los Alamos HIV Sequence Database, was used to identify
      the subtype of obtained sequence. Genetic distance between sequences was assessed
      using the software MEGA 3.1 Kimura 2-parameter, and the Phylogenetic tree was
      reestablished with Neighbor-Joining method. RESULTS: Phylogenetic tree analysis
      showed that 19 Heilongjiang strains clustered closely to subtype B strain from
      Thailand and were far from other international subtype reference strains.
      Statistical test showed no significant discrepancy between the genetic distance
      of interclass and intra-class (P > 0.05). The analysis of V3 loop amino sequence
      of 19 Heilongjiang B strains revealed that V3 tip motif of 10 samples (52.63%)
      was GPGQ, and of 4 samples (21.53%) was GPGR. CONCLUSIONS: The subtype of 19 HIV
      1 seropositive individuals in Heilongjiang Province is B', and it is introduced
      from He'nan Province. V3 tip motifs of the HIV-1 isolates are mainly GPGQ and
      GPGR.

PMID- 18067788
TI  - Modification and identification of a vector for making a large phage antibody
      library.
AB  - BACKGROUND: The large phage antibody library is used to obtain high-affinity
      human antibody, and the Loxp/cre site-specific recombination system is a
      potential method for constructing a large phage antibody library. In the present
      study, a phage antibody library vector pDF was reconstructed to construct diabody
      more quickly and conveniently without injury to homologous recombination and the
      expression function of the vector and thus to integrate construction of the large
      phage antibody library with the preparation of diabodies. METHODS: scFv was
      obtained by overlap polymerase chain reaction (PCR) amplification with the newly
      designed VL and VH extension primers. loxp511 was flanked by VL and VH and the
      endonuclease ACC III encoding sequences were introduced on both sides of loxp511.
      scFv was cloned into the vector pDF to obtain the vector pDscFv. The vector
      expression function was identified and the feasibility of diabody preparation was
      evaluated. A large phage antibody library was constructed in pDscFv. Several
      antigens were used to screen the antibody library and the quality of the antibody
      library was evaluated. RESULTS: The phage antibody library expression vector
      pDscFv was successfully constructed and confirmed to express functional scFv. The
      large phage antibody library constructed using this vector was of high diversity.
      Screening of the library on 6 antigens confirmed the generation of specific
      antibodies to these antigens. Two antibodies were subjected to enzymatic
      digestion and were prepared into diabody with functional expression. CONCLUSIONS:
      The reconstructed vector pDscFv retains its recombination capability and
      expression function and can be used to construct large phage antibody libraries.
      It can be used as a convenient and quick method for preparing diabodies after
      simple enzymatic digestion, which facilitates clinical trials and application of
      antibody therapy.

PMID- 18067789
TI  - Relationships between serum osteoprotegerin, matrix metalloproteinase-2 levels
      and bone metabolism in postmenopausal women.
AB  - BACKGROUND: Serum osteoprotegerin (OPG) and matrix metalloproteinase-2 (MMP-2)
      have been shown to play a role in bone metabolism by degrading the bone matrix.
      The present study was undertaken to compare OPG and MMP-2 with bone mineral
      density and three markers (alkaline phosphatase (AKP), calcium and phosphorus) in
      postmenopausal women in Wuhan. METHODS: Serum OPG, MMP-2, and AKP of 78 Chinese
      postmenopausal women aged 48 to 65 were measured using enzyme-linked
      immunosorbent assay (ELISA). Bone mineral density was measured with dual energy X
      ray absorptiometry (DEXA), and serum calcium and phosphorus were measured by auto
      biochemical analysis. RESULTS: Serum OPG and MMP-2 concentrations were
      significantly higher in postmenopausal women with osteoporosis ((127.6 +/- 6.3)
      ng/L; (1388 +/- 121) microg/L)) than those in age-matched normal controls ((72.3
      +/- 2.4) ng/L; (1126 +/- 141) microg/L, P < 0.01). Negative relationships were
      found between serum OPG, MMP-2 levels and bone mineral density in osteoporotic
      women. Adjusted by age and body mass index (BMI), the correlation of MMP-2 with
      bone mineral density of the neck of the femur disappeared. In osteoporotic women,
      negative correlations between OPG, MMP-2 levels and serum calcium were found (r =
      -0.216; r = -0.269, P < 0.05), but positive correlations between OPG and serum
      AKP, serum phosphorus (r = 0.235; r = 0.124, P < 0.05). CONCLUSIONS: Significant
      correlations exist between serum OPG, MMP-2 levels and bone metabolism in high
      bone turnover of postmenopausal osteoporotic women. The concentrations of serum
      OPG and MMP-2 increase possibly as a concomitant event in the high bone turnover
      state, such as postmenopausal osteoporosis. Therefore serum OPG and MMP-2 could
      be used as indicators for the bone metabolism in postmenopausal osteoporotic
      women.

PMID- 18067790
TI  - Transplantation of neonatal cardiomyocytes plus fibrin sealant restores
      myocardial function in a rat model of myocardial infarction.
AB  - BACKGROUND: Most cardiac regenerative approaches can restore injured heart
      muscles. In this study, we investigated if fibrin sealant could help neonatal
      cardiomyocytes restore myocardial function in a rat model of myocardial
      infarction. METHODS: The left anterior descending artery in adult female Sprague
      Dawley (SD) rats was ligated to make a myocardial infarction model. Neonatal
      ventricular cardiomyocytes from one-day male SD rats were isolated, labeled and
      cultured. The cells were injected into the infarcted area three weeks later. The
      animals were randomized into four recipient groups: (1) cardiomyocytes plus
      fibrin sealant (group CF, n = 10); (2) cardiomyocytes alone (group C, n = 10);
      (3) fibrin sealant recipients alone (group F, n = 10); (4) control group (n =
      10). Four weeks after transplantation, echocardiography and Langerdoff model were
      used to assess heart function. Immunohistochemical staining and polymerase chain
      reaction (PCR) were performed to track the implanted cardiomyocytes and detect
      the sex-determining region Y gene on Y chromosome. RESULTS: Echocardiography
      showed the fraction shortening (FS) in groups CF, C, F and control group was
      (27.80 +/- 6.32)%, (22.29 +/- 4.54)%, (19.24 +/- 6.29)% and (20.36 +/- 3.29)%
      respectively with statistically significant differences in group CF compared with
      the other groups (P < 0.05). The Langendoff model revealed that the left
      ventricular development of peak pressure (LVDPmax, mmHg) in groups CF, C, F and
      control group was 104.81 +/- 17.05, 80.97 +/- 21.60, 72.07 +/- 26.17 and 71.42 +/
      17.55 respectively with statistically significant differences in group CF
      compared with the other groups (P < 0.05). Pathological examination and PCR
      indicated that transplanted cardiomyocytes in group CF survived better than those
      in the other groups. CONCLUSION: Transplanted neonatal cardiomyocytes plus fibrin
      sealant can survive in myocardial infarctioned area and improve heart function
      greatly in rat models.

PMID- 18067791
TI  - Aminoguanidine delays the replicative senescence of human diploid fibroblasts.
AB  - BACKGROUND: The accumulation of free radicals and advanced glycation end products
      (AGEs) in cell plays a very important role in replicative senescence.
      Aminoguanidine (AG) has potential antioxidant effects and decreases AGE levels.
      This study aimed to investigate its effect on replicative senescence in vitro.
      METHODS: The effects of aminoguanidine on morphology, replicative lifespan, cell
      growth and proliferation, AGEs, DNA damage, DNA repair ability and telomere
      length were observed in human fetal lung diploid fibroblasts (2BS). RESULTS:
      Aminoguanidine maintained the non-senescent phenotype of 2BS cells even at late
      population doubling (PD) and increased cumulative population doublings by at
      least 17 - 21 PDs. Aminoguanidine also improved the potentials of growth and
      proliferation of 2BS cells as detected by the MTT assay. The AGE levels of late
      PD cells grown from early PD in DMEM containing aminiguanidine decreased
      significantly compared with those of late PD control cells and were similar to
      those of young control cells. In addition, the cells pretreated with
      aminoguanidine had a significant reduction in DNA strand breaks when they were
      exposed to 200 micromol/L H(2)O(2) for 5 minutes which indicated that the
      compound had a strong potential to protect genomic DNA against oxidative stress.
      And most of the cells exposed to 100 micromol/L H(2)O(2) had much shorter comet
      tails and smaller tail areas after incubation with aminoguanidine-supplemented
      DMEM, which indicated that the compound strongly improved the DNA repair
      abilities of 2BS cells. Moreover, PD55 cells grown from PD28 in 2 mmol/L or 4
      mmol/L aminoguanidine retain telomere lengths of 7.94 kb or 8.12 kb, which was
      0.83 kb or 1.11 kb longer than that of the control cells. CONCLUSION:
      Aminoguanidine delays replicative senescence of 2BS cells and the senescence
      delaying effect of aminoguanidine appear to be due to its many biological
      properties including its potential for proliferation improvement, its inhibitory
      effect of AGE formation, antioxidant effect, improvement of DNA repair ability
      and the slowdown of telomere shortening.

PMID- 18067793
TI  - Electrophysiology of hyperpolarization-activated cyclic nucleotide-gated cation
      channel 2 and hyperpolarization-activated cyclic nucleotide-gated cation channel
      4 expressed in HEK293 cells.

PMID- 18067792
TI  - Unconscious sedation/analgesia with propofol versus conscious sedation with
      fentanyl/midazolam for catheter ablation of atrial fibrillation: a prospective,
      randomized study.

PMID- 18067794
TI  - Age-related changes in dispersion of atrial effective refractory period and its
      ionic mechanism in canines.

PMID- 18067795
TI  - Diffuse panbronchiolitis in China: analysis of 45 cases.

PMID- 18067796
TI  - Management of solid renal tumour associated with von Hippel-Lindau disease.

PMID- 18067797
TI  - Thoracic exploration for the diagnosis of multiple pulmonary vein varices: case
      report.

PMID- 18067798
TI  - Successful application of nonmyeloablative stem cell transplantation for
      paroxysmal nocturnal hemoglobinuria.

PMID- 18067799
TI  - Holmes' tremor caused by midbrain cavernoma.

PMID- 18067800
TI  - Spontaneous remission of pituitary macroadenomas in women: report of two cases.

PMID- 18067801
TI  - [Attention should be paid to clinical research of ischemic preconditioning].

PMID- 18067802
TI  - [Attention-worthwhile issues in peri-operative hepatic protection].

PMID- 18067803
TI  - [Exploration of talent training on emergency response system in China].

PMID- 18067804
TI  - [Toll-like receptor 4 signal pathway may be involved in cerebral ischemic
      tolerance induced by hypoxic preconditioning: experiment with rats].
AB  - OBJECTIVE: To investigate the role of Toll-like receptor 4 (TLR4) inflammatory
      signal pathway in brain ischemic tolerance induced by hypoxia preconditioning
      (HP). METHODS: 160 Wistar rats were randomly divided into 4 groups: asphyxial
      cardiac arrest (ACA) group (n = 54, subjected to ACA for 4 min and then
      resuscitation), HP + ACA group [n = 44, subjected to apnea and ventilation (HP)
      for 1 min 4 times with an interval of 5 min between each 2 times, and then
      subjected to apnea for 4 min and resuscitation 24 h later), HP group (n = 42,
      subjected to HP 4 times only), and sham operation group (Group C, n = 20). The
      mortality within 24 h after resuscitation and circulatory functions were
      observed. Neurodeficit score (NDS) was recorded 24, 48, and 72 hours after
      successful resuscitation. Rats were killed 1, 3, 6, 12, 24, 48, and 72 h after
      preconditioning or operation to take out the left brain cortex. RT-PCR was used
      to detect the mRNA expression of TLR4. The levels of nuclear factor-kappaB
      (NFkappaB), tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-6 were
      detected by relevant kits. RESULTS: The mortality of the HP + ACA group was 5%,
      significantly lower than that of ACA group (30%, P < 0.01). The NDS levels at
      different time points of the HP group and Group C were all 100 +/- 0. The NDS
      levels of the HP + ACA group and ACA group at different time points were all
      significantly lower than those of the control group and HP group (all P < 0.01).
      The NDS levels at different time points of the ACA group were all significantly
      lower than those of the HP + ACA group (all P < 0.05). The NDS levels 72 h later
      of the HP + ACA and ACA groups were both significantly higher than those 24 h
      later of the corresponding groups (both P < 0.05). The TLR4 mRNA expression of
      the control group at any time points were all very weak, and the TLR4 mRNA
      expression level of the other groups increased since 1 h after hypoxia gradually
      and decreased 72 h later. The NFkappaB expression levels of the control group at
      any time points were all very weak, and the NFkappaB expression level of the
      other groups increased time-dependently since 1 h later, peaked 3 - 6 h later,
      and began to decrease 24 h later. There was a tendency of increase of NFkappaB
      expression level in the order of HP group < HP + ACA group < ACA group. The
      expression of TNF-alpha and IL-6 showed the same tendency as seen in the
      expression of TLR2 and NFkappaB. CONCLUSION: HP induces brain ischemic tolerance
      via a possible mechanism of activating TLR4 signal pathway and then inhibiting
      inflammatory response induced by ACA.

PMID- 18067805
TI  - [Cardioprotection of recombinant human erythropoietin pretreatment on ischemia
      reperfused hearts and mechanism thereof: experiment with rats].
AB  - OBJECTIVE: To study the cardioprotective effects of recombinant human
      erythropoietin (rhEPO) on heart with ischemia-reperfusion (I-R) injury and the
      possible mechanism. METHODS: 156 SD rats, except 36 in the sham operation group,
      underwent ligation of the left descending coronary artery for 30 minutes and then
      reperfusion for 3 hours. 108 rats were randomly divided into 3 equal groups IR +
      rhEPO group (Group C, intraperitoneally injected with rhEPO 5000 U/kg 24 h before
      IR insult), IR group (Group B), and sham-operation group (Group A). By the end of
      reperfusion blood sample were collected by cardiac puncture to detect the plasma
      content of MB isoenzyme of creatine kinase (CK-MB). Before ischemia, after
      ischemia, and 30, 60, 120, and 180 min after reperfusion the hearts of 6 rats
      from each group were killed respectively with their hearts taken out. Another 12
      rats were randomly divided into Groups B and C as described above to undergo IR
      insult, and underwent re-ligation, intravenous injection of Evans blue and
      pathological examination to observe the area of infarct size. Another 18 rats
      were divided into 3 equal groups: Groups A, B, and C as described above, and then
      underwent electron microscopy to observe the ultrastructure of the myocardium.
      Furthermore, another 18 rats were divided into 3 equal groups: Groups A, B, and C
      as described above to undergo pathological examination of the heart and
      neutrophil infiltration. Tumor necrosis-alpha (TNF-alpha) and interleukin-6 (IL
      6) concentrations of left ventricle were analyzed by ELISA 1 h and 2 h after
      reperfusion respectively; and nuclear factor-kappa B (NF-kappaB) and activator
      protein-1 (AP-1) levels were detected by electrophoretic mobility shift assay.
      RESULTS: The ratio of infarct size to area at risk (IS%) of Group C was (28.0% +/
      1.3%), significantly lower than that of Group B [(43.3 +/- 2.5)%, P < 0.01]. The
      plasma CK-MB concentrations of Groups B and C were (2110 +/- 245) U/L and (1689
      +/- 138) U/L respectively, both significantly higher than that of Group A [(933
      +/- 88) U/L, both P < 0.01], however, the CK-MB level of Group C was
      significantly lower than that of Group B (P < 0.01). The pathological changes of
      Group C were remarkably milder than those of Group B. The semi-quantitative scale
      of Groups B and C were 3.65 +/- 0.51 and 2.37 +/- 0.49 respectively, both
      significantly higher than that of Group A (1.76 +/- 0.43), and the semi
      quantitative scale of Groups C was significantly lower than that of Group B (P <
      0.01). The degree of neutrophil infiltration of Group C was remarkably milder
      than that of Group B. In Group B there were 2 peaks of NF-kappaB expression: 30
      min and 180 min after reperfusion, and the AP-1 expression increased 30 min after
      reperfusion and then gradually decreased. In Group C the expression levels of NF
      kappaB and AP-1 increased 30 min after reperfusion in comparison with Group A,
      and then gradually decreased and were all significantly lower than those of Group
      B (all P < 0.01). The levels of TNF-alpha and IL-6 1 h after reperfusion of
      Groups B and C were all significantly higher than those of Group A (all P < 0.01)
      and the TNF-alpha and IL-6 of Group C were both significantly lower than those of
      Group B (both P < 0.01). CONCLUSION: RhEPO pretreatment can elicit potent
      cardioprotection against I-R injury, which may due in part to the suppression of
      NF-kappaB and AP-1 activation and downregulation of the downstream
      proinflammatory cytokines.

PMID- 18067806
TI  - [Protection of liver against ischemia/reperfusion injury by Kupffer cell mediated
      emulsified isoflurane preconditioning: experiment with rats].
AB  - OBJECTIVE: To investigate the protective effect of pretreatment with Kupffer cell
      mediated emulsified isoflurane on ischemia/reperfusion injury in liver. METHODS:
      Thirty-two SD rats underwent partial obstruction of liver blood flow for 30 m and
      were randomly divided into 4 equal groups during the operation: lipid emulsion
      control group (Group C, pretreated with intravenous injection of lipid emulsion),
      inhibition of Kupffer cell and preconditioning with lipid emulsion control group
      (Group KC, intraperitoneally injected with gadolinium chloride, inhibitor of
      Kupffer cells, and then pretreated with intravenous injection of lipid emulsion),
      preconditioning with emulsified isoflurane group (Group IP, intravenously
      injected with emulsified isoflurane), and Inhibition of Kupffer cells and
      preconditioning with isoflurane group (Group IK, intraperitoneally injected with
      gadolinium chloride and then intravenously injected with emulsified isoflurane),
      Then liver perfusion was recovered for 2 h and the rats were killed. Blood
      samples were collected from the vena cava to detect the serum alanine
      transaminase (ALT) and aspartate transaminase (AST). Specimens of left liver
      tissue were collected to undergo light microscopy. The contents of
      malonyldialdehyde (MDA) and superoxide dismutase (SOD) in the liver homogenate
      were examined with relevant kits. RESULTS: Compared with Group C, the serum ALT
      and AST of Group IP were significantly lower (both P < 0.05). The MDA level of
      Group IP was significantly lower than that of Group C, and the SOD level of Group
      IP was significantly higher than that of Group C (both P < 0.05). However, there
      were no significant differences in the serum levels of ALT and AST and levels of
      MDA and SOD in lever homogenate among Group KC, IK, and C. The pathological
      changes in liver were remarkably milder in Group IP then in Group C, however,
      there were no significant differences in the pathological changes among Groups
      KC, IK, and C. CONCLUSION: Preconditioning with emulsified isoflurane protects
      the liver from ischemia/reperfusion injury and this effect me be mediated by
      Kupffer cells.

PMID- 18067807
TI  - [Protective effects of propofol preconditioning on cardiopulmonary bypass-induced
      apoptosis: report of 40 cases].
AB  - OBJECTIVE: To investigate the protective effects of propofol preconditioning on
      cardiopulmonary bypass (CPB)-induced apoptosis and its possible mechanism.
      METHODS: Forty patients undergoing CPB were randomly divided into 2 equal groups:
      propofol preconditioning group (Group P, pre-treated with propofol 2 mg/kg pre
      operatively and 5 mg.kg(-1).h(-1) intra-operatively) and control group (Group C,
      pre-treated with midazolam 0.2 mg/kg pre- and 0.1 mg.kg(-1).h(-1) intra
      operatively). Specimens of right auricle tissue were taken before and after CPB
      to undergo HE staining and electron microscopy to observe the changes of
      mitochondria. TUNEL technique was used to detect the apoptotic cells and the
      apoptotic index (AI) was calculated. Avidin biotin complex method was used to
      detect the expression of caspase-9 and caspase-3. RESULTS: The rate of
      spontaneous restoration of beats of Group P was 65%, significantly higher than
      that of Group C (30%, P < 0.05). The amount used of dobutamine within 12 h post
      operatively of Group P was 4.6 +/- 1.1 microg.kg(-1).h(-1), significantly lower
      than that of Group C (7.8 +/- 1.0 microg.kg(-1).h(-1), P < 0.05). The ICU stay
      time of Group P was 40 +/- 6 h. significantly shorter than that of Group C (58 +/
      7 h, P < 0.05). The specimens taken after CPB showed that in comparison with
      Group C the mitochondria were relatively intact with clear ridges and
      intermembrane spaces in Group P. The AI after CPB of Group C was (19.3 +/- 3.5)%,
      significantly higher than that before CPB [(7.1 +/- 1.4)%, P < 0.05] and the
      corresponding level of Group P [(10.9 +/- 1.4)%, P < 0.05]. The expression levels
      of Caspace-9 and Caspace-3 after CPO of Group C were both significantly higher
      than those before CPB (both P < 0.05), and the corresponding levels of Group P
      (both P < 0.05). CONCLUSION: Propofol preconditioning significantly inhibits CPB
      induced cardiomyocyte apoptosis and the mechanism is associated with protecting
      the mitochondria and down-regulating the expression of caspase-9 and caspases-3.

PMID- 18067810
TI  - [Prenatal ultrasonography for fetus with hydronephrosis].
AB  - OBJECTIVE: To investigate the relationship between classification and prognosis
      of hydronephrosis in fetus. METHODS: 226 pregnant women in their pregnant weeks
      20 - 40 who were suggested to be with fetuses suffering from hydronephrosis
      underwent ultrasonography to observe the configuration of the kidneys, form and
      size of renal pelvis, extent of calyces, and thickness of renal cortex of their
      fetuses. The ultrasonography was conducted regularly and the outcome after birth
      was followed up. RESULTS: 143 fetuses (186 kidneys) were diagnosed as with
      hydronephrosis of grade I with the anteroposterior diameter of the renal pelvis
      from 0.3 to 1.1 cm that fadeawayed soon after birth with a good prognosis. 47
      fetuses (52 kidneys) were diagnosed as with hydronephrosis of grade II with the
      anteroposterior diameter of the renal pelvis from 1.0 to 1.8 cm, most of which
      remised gradually after birth, and only about 5% of which became worse along with
      the time of pregnancy and needed surgery after birth. 10 fetuses (10 kidneys)
      were diagnosed as with hydronephrosis of grade III with the anteroposterior
      diameter of the renal pelvis from 1.5 to 3.3 cm about 70% of which showed a
      tendency to deteriorate along with the time of pregnancy and after birth, and the
      neonates needed surgery after birth. Eight fetuses (10 kidneys) were diagnosed as
      with hydronephrosis of grade IV with the anteroposterior diameter of renal pelvis
      from 1.5 to 7.2 cm that needed surgery after birth. CONCLUSION: Follow-up and
      monitoring are not necessary for those fetus with hydronephrosis of grade I;
      however, regular ultrasonography is needed for the those with hydronephrosis of
      grade II and over.

PMID- 18067809
TI  - [Serum screening of fetal chromosome abnormality during second pregnancy
      trimester: results of 26,803 pregnant women in Jiangsu Province].
AB  - OBJECTIVE: To evaluate the efficiency of the second trimester screening for fetal
      chromosomal anomaly using maternal serum marker. METHOD: 27,313 pregnant women
      with the gestational age of 15 - 20 weeks were selected by stratified combined
      with cluster sampling from 13 counties over Jiangsu province and 5 townships,
      towns, or subdistricts from 6 randomly selected cities from southern, central,
      and northern Jiangsu, totally 95 communities, between July 2002 and November
      2006. Questionnaire survey was conducted. Body weight was taken. Ultrasonography
      was used to confirm the gestational age. Peripheral blood samples were collected
      to detect the maternal serum alpha-fetoprotein (AFP) and free beta human
      chorionic gonadotrophin (f-betaHCG). The risk values of Down syndrome and Edwards
      syndrome were calculated. The women at high risk of Down syndrome and Edwards
      syndrome for their fetuses were recommended to receive genetic counseling and
      amniocentesis. All babies were followed up until six months to four years of age
      after birth. RESULTS: 26,803 of the 27,313 women (98%) were screened. The average
      was 25.1, and 1.7% of them were over 35. Serum screening showed that 1,244 (5%)
      were Down syndrome positive and 105 (0.4%) were Edwards syndrome positive. The
      final pregnant outcomes showed that 20 cases presented chromosomal abnormalities,
      of which 9 cases suffered from Down syndrome, 5 cases Edwards syndrome, and 6
      cases other chromosomal abnormalities. The detection rate of Down syndrome and
      Edwards syndrome were 56% and 80% respectively. CONCLUSION: Under good quality
      control high prenatal detection rate of fetal chromosomal abnormalities can be
      reached by screening of maternal serum AFP and f-betaHCG during the second
      pregnancy trimester. Good cost-effectiveness depends on the incidence of targeted
      birth defects.

PMID- 18067811
TI  - [Assessment of curve flexibility in adolescent idiopathic scoliosis before
      operation].
AB  - OBJECTIVE: To compare the effects in assessing the curve flexibility of the
      adolescent idiopathic scoliosis (AIS) and predicting the outcomes of operation
      among different radiological techniques: supine lateral bending (SB), traction
      (Tr), and fulcrum bending radiographs. METHODS: 68 consecutive AIS patients, all
      with the single-curve types Ia/Ib/Ic according to the PUMC classification,
      divided into 4 groups according to the magnitude of Cobb's angle: moderate
      thoracic curve (n = 19, 40 degrees < Cobb's angle < or = 60 degrees ), severe
      thoracic curve (n = 13, Cobb's angle > 60 degrees ), moderate lumbar curve (n =
      28, 35 degrees < Cobb's angle < or = 60 degrees ), and severe lumbar curve(n = 8,
      Cobb's angle > 60 degrees ) who were treated surgically underwent preoperative
      radiological evaluation including standing anteroposterior and lateral Tr, SB,
      and fulcrum bending radiographs. COBB angle was measured and the flexibility
      ratio was determined on each radiograph. The amounts of correction obtained by
      all radiographic methods were compared with the amount of surgical correction.
      RESULTS: The post-operative Cobb's angle of the moderate thoracic curve group was
      9 degrees , not significantly different from that by fulcrum bending radiograph
      (P = 0.076), but significantly different from those by the other methods (both P
      < 0.01). The post-operative COBB angle of the severe thoracic curve group was 40
      degrees , significantly different from all the radiographs before operation (all
      P < 0.01). The post-operative Cobb's angle of the moderate lumbar curve group was
      4 degrees , significantly different from those by fulcrum bending and Tr
      radiographs (both P < 0.01) and that by SB (P = 0.013). The post-operative Cobb's
      angle of the severe lumbar curve group was 24 degrees , significantly different
      from those of anteroposterior and Tr radiograph (both P < 0.01) and those of
      fulcrum-bending and SB radiographs (P = 0.021 and P = 0.011). In the moderate
      thoracic curve group the operation correction rate was not significantly
      different from the flexibility rate by fulcrum-bending radiograph (P = 0.111),
      and was significantly different from the flexibility rates by SB and Tr
      radiographs (P = 0.011 and P = 0.000). In the severe thoracic curve group the
      operation correction rate was significantly different from the flexibility rates
      by different kinds of radiograph (all P = 0.111). In the moderate lumbar curve
      group the operation correction rate was significantly different from the
      flexibility rates by different kinds of radiograph (P < 0.111 or P = 0.019). In
      the severe lumbar curve group the operation correction rate was significantly
      different from the flexibility rates by different kinds of radiograph (P < 0.01
      or P = 0.017). CONCLUSION: Fulcrum-bending radiography can better assess the
      flexibility and correction rate of thoracic curves in AIS, however, it can only
      predict those in moderate thoracic curves. Fulcrum-bending radiograph and SB
      radiograph are similar in predicting the flexibility in lumbar curves.

PMID- 18067812
TI  - [Comparison of the acetabular orientation after minimally-invasive total hip
      arthroplasty with and without computer-navigation: a clinical report of 106 hip
      in 87 patients].
AB  - OBJECTIVE: To evaluate the acetabular angle after minimally-invasive total hip
      arthroplasty (MIS-THA) with or without computer-navigation. METHODS: 87
      consecutive orthopedic patients (106 hips) underwent MIS-THA with computer
      navigation (40 cases with 53 hips) or without computer-navigation (47 cases with
      53 hips). The full leg length and pelvis were measured with radiography
      preoperatively and post-operatively. RESULTS: The average length of incision of
      the navigation group was 8.9 cm (7.8 - 10.5 cm), and the average length of
      incision of the non-navigation group was 9.1 cm (7.5 - 11 cm) The average cup
      inclination on the plain post-operative radiography of the navigation group was
      40.58 degrees +/- 5.09 degrees (30 degrees - 54 degrees ), only the cup abduction
      being 54 degrees , significantly less steep than that of the control group [44.17
      degrees +/- 8.71 degrees (28 degrees - 70 degrees , t' = 2.56. P = 0.012). Among
      the 47 control cases 40 cases showed the cup abduction of 30 degrees - 50 degrees
      , 3 showed the cup abduction of < 30 degrees , and 10 showed the cup abduction of
      > 50 degrees . The computer-navigation MIS-THA was significantly more accurate
      than the conventional MIS-THA. Pearson chi-square test showed that there was not
      significant difference in the percentage of cases with acetabular abduction < 30
      degrees , between these two groups (chi(2) = 1.37, P = 0.24), and there was a
      significant difference in the percentage of cases with acetabular abduction > 50
      degrees , between these two groups (chi(2) = 8.22, P = 0.0042). There was a
      significant difference in the percentage of cases with the acetabular abduction <
      30 degrees and > 50 degrees calculated together between these 2 groups (chi(2) =
      11.85, P = 0.0006), CONCLUSION: MIS-THA with computer-navigation allows accurate
      orientation of the cup implant components without direct visualization of the
      bony landmarks.

PMID- 18067815
TI  - [Combination of stereotactic lesion and multiple subpial transsection in
      treatment of bitemporal lobe epilepsy: report of 12 cases].
AB  - OBJECTIVE: To explore the effect of combination of stereotactic lesion and
      multiple subpial transsection (MST) in treatment of bitemporal lobe epilepsy
      (BTLE). METHODS: Independent epileptogenic foci were found in bilateral temporal
      lobes by video-electroencephalogram, computed tomogrphy, magnetic resonance
      imaging, magnetic resonance spectroscopy, positron emission tomography-computed
      tomography, magnetoencephalography, neuropsychology and intraoperative
      electrocoticography, and depth EEG in 12 patients with intractable epilepsy. Then
      the BTLE patients were treated with stereotactic amygdalohippocampotomy (SAHT)
      and MST respectively according to the sites of the. epileptogenic foci: in the
      amygdalohippocampus complex or temporal neocortex. Followed-up was conducted for
      6 - 32 months. RESULTS: The curative effects of the 12 patients according to
      Engel's standard were grade I in 5 cases, grade II in 3 case, grade III in 3
      cases, and grade IV in 1 case. No permanent complication was found. CONCLUSION:
      Combination of SAHT and MST procedures is safe and effective in treatment of
      bitemporal lobe epilepsy.

PMID- 18067814
TI  - [Expression of fascin and cytokeratin 14 in esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the expression of fascin and cytokeratin 14 (CK14) in
      human esophageal squamous cell carcinoma (ESCC) and the association of these two
      proteins with ESCC malignant progression and the possibility of application of
      these 2 proteins in the diagnosis of ESCC. METHODS: A tissue microarray composed
      of the representative regions of ESCC and corresponding normal epithelium was
      constructed. Immunohistochemistry was conducted to examine the expression of
      fascin and CD14 in 116 specimens of ESCC and the normal tissues near the
      cancerous tissues. The relation of these two proteins with the invasive depth,
      node involvement, differentiated grade, pTNM stages was analyzed. Disease-free
      survival analysis was carried out using Kaplan-Meier method. The correlation of
      the two proteins was analyzed using Spearman's correlation test. ESCC cells of
      the lines EC9706, TE12, COLO-680N, KYSE510, KYSE450, KYSE410, KYSE180, KYSE150,
      KYSE140, KYSE70, KYSE30, and YES2 were cultured and underwent SDS-PAGE and
      Western blotting to examine the expression of fascin and CD14. And the
      correlation of the two proteins with the characteristics of the cell lines was
      analyzed too. RESULTS: Fascin and CK14 were negative in the normal esophageal
      epithelia except in the basal cells. The positive rates of fascin and CK14 in the
      ESCC cells were 79.3% and 67.0% respectively. The positive rate of either fascin
      or CK14 was 86.2%. The expression rates of fascin and CK14 in well- and
      moderately-differentiated ESCCs were significantly higher than that in the poorly
      differentiated ones (P = 0.054 and P < 0.01). The patients with positive
      expression of fascin and those with negative expression of CK14 had a poorer
      survival in comparison with those with negative fascin expression and those with
      positive CK14 expression respectively, however, without statistical significances
      (P = 0.8980 and P = 0.2610). The positive rates of fascin in the well-,
      moderately-, and poorly- differentiated ESCCs were 87.1%, 83.9%, and 62.1%
      respectively (P = 0.054). The positive rates of CK14 in the well-, moderately-,
      and poorly-differentiated ESCCs were; 87.1%, 76.4%, and 27.6% respectively (P <
      0.01). The prognosis was not significantly correlated with the expression of both
      proteins (P = 0.8980 and P = 0.2610). There was an significantly positive
      correlation between the expression levels of these 2 proteins (r = 0.487, P <
      0.01). Fascin was highly expressed in most of the ESCC lines, except in the
      slowly growing and weakly migrating TE12 line. High expression of CK14 was only
      seen in the line KYSE180. CONCLUSION: Fascin and CK14 may play important roles in
      the carcinogenesis and progression of ESCC. Combination of fascin and CK14 would
      be valuable markers in diagnosis of ESCC.

PMID- 18067816
TI  - [Protection of ulinastatin against myocardial injury induced by off-pump coronary
      artery bypass graft surgery: report of 24 cases].
AB  - OBJECTIVE: To investigate the protective effect of ulinastatin against myocardial
      injury induced by off-pump coronary artery bypass graft surgery (OPCAB). METHODS:
      Twenty-four patients undergoing OPCAB were randomly divided into 2 equal groups:
      ulinastatin group in which ulinastatin was infused intravenously, firstly at the
      concentration of 6000 U/kg dissolved in 50 ml normal saline for 30 min and then
      at the speed of 1000 U.kg(-1).h(-1) up to the end of operation, and control group
      that underwent infusion of normal saline of the same volume. Blood samples were
      collected before skin incision, 0.5 h after the completion of vascular
      anastomosis, and 2, 6, and 18 h after the operation to detect the plasma level of
      cardiac troponin 1 (cTn1). RESULTS: The cTn1 levels 2, 6, and 18 h after the
      operation of both groups were all significantly higher than those before skin
      incision (all P < 0.01). The cTn1 levels 0.5 h after the completion of vascular
      anastomosis, and 2, 6, and 18 h after the operation of the ulinastatin group were
      all significantly lower than those of the control group (all P < 0.01).
      CONCLUSION: Ulinastatin decreases the cTn1 level that increases peri-operatively,
      thus reducing the risk of myocardial injury in patients undergoing OPCAB.

PMID- 18067817
TI  - [Immunopathology of labial glands of patients with primary Sjogren's syndrome].
AB  - OBJECTIVE: To investigate the expression of CD4+CD25+ regulatory T cell (Treg) in
      labial gland (SG) of the patients with Sjogren's syndrome (SS). METHODS:
      Specimens of labial gland were obtained from 25 primary SS patients and 6 healthy
      controls during biopsy to be made into serial sections. Immunohistochemistry was
      used to examine the expression of CD25, CD4, CD8, CD68 and Foxp3. RESULTS:
      Infiltration of a great amount of mononuclear cells and atrophy of part of the
      labial glands were seen in the specimens from SS patients. The percentage of CD4+
      T cells in the infiltrating leucocytes of the SS patients was (44.2 +/- 20.5)%,
      significantly higher than that of the controls [(9.2 +/- 6.0)%, P < 0.01]. CD25
      and Foxp3 were completely absent in the specimens from both the controls and SS
      patients. CONCLUSION: CD4+CD25+ regulatory T cell lacks in the labial gland of SS
      patients. CD4+CD25+ regulatory T cells play a key role in the progression of SS.

PMID- 18067818
TI  - [Effect of hypertonic medium on expression of aquaporin-1 in pleural mesothelial
      cells: experiment with rats].
AB  - OBJECTIVE: To study the expression of aquaporin-1 (AQP-1) in pleural mesothelial
      cells (PMCs) and the influence of hypertonic medium thereupon. METHODS: Rat PMCs
      were isolated, cultured, and divided into 2 groups: hypertonic group, cultured in
      hypertonic media with NaCl of different concentrations for 24 h and control
      group, cultured in D-MEM/F-12 medium. The 100 mmol/L NaCI group was examined at
      the time points 6, 12, 18, and 24 h respectively. RT-PCR and Western blotting
      were used to analyze the mRNA and protein expression of AQP-1. RESULTS: The A
      values of AQP-1 protein expression were 24.0 +/- 1.8, 27.8 +/- 2.4, 31.7 +/- 2.5,
      89.7 +/- 6.2, and 107.7 +/- 9.3 respectively in the PMCs treated with hypertonic
      media with NaCl of the concentrations of 25, 50, 75, 100, and 150 mmol/L, all
      significantly higher than that in the control group (10.8 +/- 1.5, all P < 0.01).
      The A values of AQP-1 protein expression were 42.1 +/- 2.6, 78.9 +/- 3.6, 109.6
      +/- 7.6, and 123.4 +/- 8.7 in the PMCs treated with hypertonic media with NaCl of
      the concentration of 100 mmol/L after 6 h, 12 h, 18 h, and 24 h, all
      significantly higher than that in the control group (12.9 +/- 1.9, P < 0. 01).
      The a values of AQP-1 mRNA expression were 62.6 +/- 6.4, 75.3 +/- 5.5, 122.3 +/-
      11.4, 196.2 +/- 18.1, and 223.0 +/- 19.3 respectively in the PMCs treated with
      hypertonic media with NaCl of the concentrations of 25, 50, 75, 100, and 150
      mmol/L, all significantly higher than that in the control group (23.5 +/- 2.7,
      all P < 0.01). The A values of AQP-1 protein expression were 83.6 +/- 6.1, 159.3
      +/- 6.9, 266.2 +/- 24.1, and 196.2 +/- 15.7 in the PMCs treated with hypertonic
      media with NaCl of the concentration of 100 mmol/L after 6 h, 12 h, 18 h, and 24
      h, all significantly higher than that in the control group (26.5 +/- 2.8, P <
      0.01). CONCLUSION: Hypertonic medium increases the expression of AQP-1 mRNA and
      protein. AQP-1 participates in the pleural fluid formation.

PMID- 18067819
TI  - [Effects of follicle stimulating hormone on proliferation, apoptosis, migration
      and invasion of ovarian carcinoma cells: an in vitro experiment].
AB  - OBJECTIVE: To investigate the effects of follicle stimulating hormone (FSH) on
      the proliferation, apoptosis, migration and invasion of ovarian cancer cells.
      METHODS: Ovarian cancer cells of the lines SKOV-3 and ES-2 were cultured, and
      treated by FSH of the concentrations of 10, 20, 40, 80, and 160 mU/ml for 48 h or
      24 h respectively. The cells without FSH treatment were used as control cells.
      The proliferative effects of the cells were detected by MTT colorimetry. The
      apoptosis and cell cycle were examined by flow cytometry. The matrix
      metalloproteinases-2 (MMP-2) protein levels in the supernatant were determined by
      zymography. The cytoplasm levels of MMP-2 protein in cells were tested by Western
      blotting. RT-PCR was used to detect the expression of MMP-2 mRNA in cells. The
      migration and invasion of the cells were examined. RESULTS: The a values of the
      SKOV-3 treated with FSH of the concentrations of 10 - 160 mU/ml were all
      significantly higher than those without FSH treatment (all P < 0.01). The
      apoptosis rates of the SKOV-3 treated with FSH of the concentrations 10 - 160
      mU/ml were (0.94 +/- 0.06)%, (0.71 +/- 0.03)%, (0.22 +/- 0.02)%, (0.32 +/-
      0.02)%, and (0.55 +/- 0.05)% respectively, all significantly lower than those
      without FSH treatment [(1.30 +/- 0.10)%, all P < 0.01]. After treatment with FSH
      of the concentrations 40 to 160 mU/ml the percentages of the SKOV-3 at the stage
      G(0)/G(1) gradually decreased and the cells at the stage S gradually increased
      compared with the control groups (all P < 0.05). The MMP-2 mRNA and protein
      expression levels of the SKOV-3 increased with the concentration increase of FSH
      (P < 0.05 or P < 0.01). Boyden chamber invasive assay showed that the numbers of
      the SKOV-3 that penetrated the basement membrane were (157 +/- 20)/hp (x200),
      significantly higher than those of the control groups [(27 +/- 9)/hp, P < 0.01].
      Scarification test showed that the distance between scratches of the FSH-treated
      SKOV-3 cells was significantly shorter than that of the control group (P < 0.01).
      FSH also induced similar results in ES-2 cells. CONCLUSION: FSH induces the
      proliferation, migration, and invasion and suppresses the apoptosis of ovarian
      cancer cells.

PMID- 18067820
TI  - [mRNA expression and activity of ADAM17 in hippocampus after chronic cerebral
      hypoperfusion: experiment with aged rats].
AB  - OBJECTIVE: To explore the effect of alpha-secretase on the pathogenesis of
      cognitive impairment following cerebral ischemia. METHODS: Forty-eight 12~16
      months-old Wistar rats were randomly divided into 2 equal groups: hypoperfusion
      group, undergoing permanent occlusion of bilateral common carotid arteries to
      mimic cerebral hypoperfusion, and sham-operation group. Each group was further
      divided into 1, 2, 4, and 16 week subgroups. Y-maze test was conducted before
      operation and at different time points as mentioned above to examine the spatial
      learning and memory ability. The rats tested by Y-maze were killed with their
      hippoccampi taken out. Realtime PCR was used to assay the mRNA expression of a
      disintegrin and metalloproteinase (ADAM)-17 representing alpha-secretase in the
      hippocampus, and fluorescence spectrometry was applied to measure activity
      thereof. RESULTS: The numbers of electric stroke since 2 weeks after
      hypoperfusion were significantly higher than that before hypoperfusion in the
      same group and those of the sham-operation group (P < 0.05 or P < 0.01). The mRNA
      expressions of hippocampal ADAM17 of the hypoperfusion subgroup 2, 4, and 16
      weeks after operation were 0.78 +/- 0.03, 0.78 +/- 0.02, and 0.54 +/- 0.03
      respectively, all significantly lower than those of the sham-operation group
      (1.12 +/- 0.05, 0.99 +/- 0.04, and 1.01 +/- 0.04 respectively, all P < 0.01). The
      average fluorescence values of hippocampal alpha-secretase 1, 2, 4, and 16 weeks
      after hypoperfusion of the hypoperfusion group were 33,880 +/- 1086, 37,496 +/-
      817, 32,295 +/- 864 and 30,069 +/- 1111, respectively, all significantly lower
      than those of the sham-operation group (39 497 +/- 838, 39 802 +/- 1052, 40,137
      +/- 776, and 39,894 +/- 1076 respectively, all P < 0.01). CONCLUSION: The mRNA
      expression of ADAM17 that represents alpha-secretase in the hippocampus is down
      regulated and the activity of alpha-secretase is decreased after chronic cerebral
      hypoperfusion. That may subsequently result in accumulation of beta amyloid
      precursor protein, substrate of alpha-secretase, (APP), and then activate the
      other pathway cleaving APP, i.e., the pathway by beta secretase. At last, the
      production of beta amyloid protein in brain after chronic cerebral hypoperfusion
      increases and impairs the memory.

PMID- 18067822
TI  - [Sequencing of SLC26A4 exons 7 and 8 and hot spot mutation analysis in 1552
      moderate to profound sensorineural hearing loss patients in China].
AB  - OBJECTIVE: To investigate the hot spot mutation of SLC26A4 gene and its incidence
      among patients with moderate to profound sensorineural hearing loss (SNHL) and to
      analyze the epidemiology of enlarged vestibular aqueduct syndrome in China.
      METHODS: Peripheral blood samples were collected from 1,552 students of deaf and
      dumb school in 21 cities throughout China. The nationality distribution of the
      1,552 students included Han (n = 1290), Uigur (n = 69), Hui (n = 37), Mongolian
      (n = 31), and Southwest minorities including Yi, Zhuang, Bai, Miao and other 14
      nationalities (n = 125). The hot spot mutation IVS7-2A > G and other mutations in
      the SLC26A4 exons 7 and 8 with intron 7 were analyzed by direct sequencing.
      RESULTS: Mutation in the SLC26A4 exons 7 and 8 or intron 7 were found in 199
      students, of whom 83 carried IVS7-2A > G homozygous mutation, 114 carried IVS7-2A
      > G heterozygous mutation, and the other two carried two other kinds of mutation.
      Of the 1,552 cases, the percentage of cases carrying IVS7-2A > G mutation was
      12.7% (197/1,552), and this percentage reached up to 14.3% in 1,290 cases of Han
      nationality, while in the 69 cases of Uigur nationality this ratio was 0. The
      prevalence rates of IVS7-2A > G mutation in Zhuozhou and Gaobeidian, Hebei
      province, and Anyang, Henan province, were 24.7% and 28.3% respectively, both
      significantly higher than the percentages of the whole China and other regions
      (all P < 0.05). CONCLUSION: Hereditary SNHL caused by SLC26A4 mutations accounts
      for a high percentage in China. It is of great importance to screen SLC26A4 gene
      for making etiological diagnosis for deafness. Screening of the hot spot mutation
      of IVS7-2A > G is of advantage for large scale screening among patients with
      deafness.

PMID- 18067823
TI  - [Surface enhanced laser desorption/ionization time-of-flight mass spectrometry
      profiling of serum in detection of laryngeal squamous cell carcinoma and the
      progression to lymph node metastasis].
AB  - OBJECTIVE: To assess the use of surface enhanced laser desorption/ionization time
      of-flight mass spectrometry (SELDI-TOF MS) to identify multiple serum protein
      biomarkers for early detection of laryngeal squamous cell carcinoma (LSCC), to
      establish predictive model, and to accurately distinguish LSCC patients with or
      without lymph node metastasis. METHODS: Serum samples were collected from 142
      LSCC patients and 110 normal controls, totally 252, and randomly divided into 2
      groups: model establishment group (including 89 patients with LSCC at the stages
      I and II, 30 of which had lymph node metastasis, and 65 normal controls) and
      blind test group (including 53 patients with LSCC at the stages III and IV and 45
      normal controls). Serum protein profiling on weak cationic exchange (WCX2) was
      performed by SELDI-TOF MS and the results were analyzed by Biomarker Wizard
      software. The Decision Tree classification algorithm and blind validation were
      determined by Biomarker Pattern software (BPS). RESULTS: A panel of 18 biomarkers
      ranging from 2,000 to 50,000 was selected based on their collective contribution
      to the optimal separation between the LSCC patients and healthy controls. Among
      them 1 candidate protein peak with the M/Z value of 4,176 was selected to
      establish predictive model by BPS with the sensitivity of 86.52% and the
      specificity of 84.62%. The ability to detect LSCC patients was evaluated using
      blind test data in cancer patients. The sensitivity of the blind test was 84.91%,
      and the specificity was 82.22%. 14 potential biomarkers were found to
      differentiate the LSCC patients with or without lymph node metastasis (P < 0.05).
      CONCLUSION: The high sensitivity and specificity achieved by the serum protein
      biomarkers show great potential for the early detection of LSCC. SELDI-TOF MS
      serum profiling is able to distinguish LSCC patients with or without lymph node
      metastasis.

PMID- 18067824
TI  - [Diagnosis and treatment of focal nodular hyperplasia of liver: report of 23
      cases].
AB  - OBJECTIVE: To report the experience in the diagnosis and treatment of focal
      nodular hyperplasia (FNH) of liver. METHODS: The clinical data of 23 patients
      with FND in liver, 15 males and 8 females, aged 38 (22 - 53), were analyzed
      retrospectively. RESULTS: Thirteen of the 23 patients had been diagnosed as with
      FNH of liver before operation. The diagnosis of 12 cases was confirmed by CT or
      MRI. One case underwent ultrasonography guided biopsy. The diameters of tumor
      ranged 0.8 - 8 cm. All the 23 patients underwent resection of tumor with an
      uneventful recovery and without recurrence during the follow-up period.
      Altogether 27 tumor nodes had been resected. The diagnosis was confirmed by
      histological examination in all of the patients. CONCLUSION: CT and MRI are
      valuable for the diagnosis of FH of liver. Biopsy guided by ultrasonography leads
      to histological diagnosis. However, definite preoperative diagnosis remains
      difficult to make. Surgical resection is necessary when the patient becomes
      symptomatic or when malignancy cannot be excluded.

PMID- 18067825
TI  - [Flow simulation of normal pulmonary artery branches based on multiple detectors
      computed tomography].
AB  - OBJECTIVE: To simulate the flow condition in the main pulmonary artery and the
      branches of left and right pulmonary arteries by combining the images from CT
      pulmonary angiography (CTPA) by multiple detectors computed tomography (MDCT) and
      the flow condition data from ultrasonic cardiography. METHODS: The normal
      enhanced chest CTPA images with ECG-gating from 25 persons undergoing physical
      examination, 21 males and 4 females, aged 39, underwent thin-slice multiple plane
      reconstruction in diastolic and systolic periods respectively. These images were
      stored in the InSpace software. On the base of coordinates GAMBIT software was
      used to generate the nodes and meshes. FLUENT software was used to simulate the
      blood flow speed and pressure field distribution. RESULTS: The pressure levels of
      the main pulmonary artery and the branches of left and right pulmonary arteries
      were higher during the systolic period. The blood flow velocity was faster during
      the systolic period too. The right lower lobe artery endured the most significant
      pressure during both systolic and diastolic periods. However, there were not
      significant differences in pressure and blood flow velocity between the systolic
      and diastolic periods in the segmental arteries. CONCLUSION: The right lower lobe
      artery is the first part to be affected when the pulmonary pressure rises. It is
      feasible to study the changes of the flow condition in the branches of pulmonary
      artery through combining CTPA images and relevant softwares.

PMID- 18067826
TI  - [Prevalence and predictors of microalbuminuria in persons with various glucose
      tolerance levels].
AB  - OBJECTIVE: To investigate the prevalence of microalbuminuria in persons with
      various glucose tolerance levels and the risk factors for the development of
      microalbuminuria. METHODS: Early morning urine samples were collected from 1,779
      subjects with all the data necessary for this survey from a population screened
      in Baoshan Community, Shanghai by cluster sampling, including 752 with normal
      glucose tolerance (NGT), 505 impaired glucose tolerance (IGR), and 522 type 2
      diabetes mellitus (T2DM) diagnosed according to a 75 g oral glucose tolerance
      test (OGTT). Urinary albumin-to-creatinine ratio (ACR) was measured by rate
      nephelometry method. RESULTS: (1) The incidence rate of MAU of the T2DM group was
      11.3%, significantly higher than those of the NGT and IGR groups (4.7% and 6.1%
      respectively, both P < 0.01). (2) Logistic regression showed that MAU was
      significantly correlated with 2 h PG, systolic blood pressure, and triglyceride.
      CONCLUSION: The prevalence of MAU is significantly higher in the diabetic
      patients. 2 h PG, systolic blood pressure, and triglyceride and independent risk
      factors of MAU.

PMID- 18067828
TI  - [Expression of desmoglein 3 in nasopharyngeal carcinoma: research of 22 cases].
AB  - OBJECTIVE: To investigate the expression of desmoglein 3 (DSG3), a candidate
      target gene in the antisense RNA (aRNA) from the purified nasopharyngeal tissues
      in nasopharyngeal carcinoma (NPC). METHODS: Specimens of nasopharyngeal tissues
      were harvested from 22 NPC patients, aged 44 +/- 11 (NPC group), and 12 normal
      persons or patients with nasopharyngeal infectious diseases, aged 46 +/- 14.
      Microdissection technique was used to get homogenous tissue cells from which
      total RNA was isolated (control group). aRNA was amplified from the total RNA by
      "in vitro transcription" (IVT). The expression of DSG3 gene was identified using
      these aRNA by semi-quantitative reverse transcriptase polymerase chain reaction
      (sqRT-PCR). RESULTS: The average expression level of DSG3 in the NPC group was
      3.536 +/- 2.689, significantly higher than that of the control group (0.95 +/-
      0.23, df = 32, t = 3.307, P = 0.002). The expression level of DSG3 in the whole
      expression profiling of the NPC group was 1.06 +/- 1.60, significantly higher
      than that of the control group (0.48 +/- 0.23, df = 16, t = 2.145, P = 0.048).
      CONCLUSION: The whole genome expression profiling detected by sqRT-PCR can be
      used to shift the marker genes from biopsy tissue samples. DSG3 may be a tumor
      candidate gene in NPC.

PMID- 18067829
TI  - [Early diagnosis of bladder cancer by special fluorescence spectrum: an in vitro
      experiment].
AB  - OBJECTIVE: To investigate the value of special fluorescence spectrum in the early
      diagnosis of bladder cancer. METHODS: Hematoporphyrin monomethyl ether (HMME) of
      the concentrations of 10, 100, and 200 microg/ml, as photosensitizer, was added
      into the sample vessels of bladder cancer tissue to be incubated for 1 - 3 h. A
      detecting system consisting of solid state ultraviolet laser with the wavelength
      of 355 nm was used to measure the fluorescence spectrum. RESULTS: The laser
      induced auto-fluorescence (LIAF) of the bladder cancer tissue had characteristic
      double peaks at 445 - 490 nm. There was a remarkable characteristic peak, drug
      peak, located at 628.25 nm in the laser-induced drug-fluorescence (LIDF) of the
      bladder cancer tissue soaked by HMME. CONCLUSION: Photosentisizer raise the
      sensitivity and specificity of fluorescence spectrum in diagnosis of bladder
      cancer. Stable, and with high strength and visible drug peak, the LIDF is may
      help improve the early diagnosis of bladder cancer.

PMID- 18067830
TI  - [Factors for recurrence of primary retroperitoneal sarcoma: analysis of 77
      cases].
AB  - OBJECTIVE: To explore the factors influencing the recurrence of retroperitoneal
      sarcoma. METHODS: The clinical data of 77 patients with primary retroperitoneal
      sarcoma who were treated with surgery between Jan 1980 and Dec 2005 and followed
      up for 45.7 months (3.6 - 180.4 months), 36 males and 41 females, aged 49 (24 -
      75). RESULTS: 57 cases developed local recurrence and 3 had metastases after
      surgery. The overall recurrence rate was 74%. The median time between initial
      surgery and recurrence was 14.8 months (3.2 - 99.6 months). 27 patients died of
      sarcoma and 5 die of other reasons. The median survival time was 42.5 months (3.6
      - 180.4 months). The overall 5-year and 10-year survival rates were 61.7% and
      43.9% respectively, and the 5-year and 10-year relapse-free survival rates were
      22.7% and 16.8% respectively. Univariate analysis showed that incomplete tumor
      resection and high-grade tumor were associated with the increased local
      recurrence rate (P = 0.0008 and P = 0.018). Cox multivariate analysis showed that
      the only factor found to decrease the risk of local recurrence was complete tumor
      resection (P = 0.001). CONCLUSION: Complete surgical resection at the time of
      primary tumor presentation affords the best chance for local control. Patients
      with high-grade tumor should on the alert for local relapse after surgery.

PMID- 18067831
TI  - [Comparative study of laparoscopic partial nephrectomy and traditional open
      procedure: analysis of 26 cases].
AB  - OBJECTIVE: To evaluate the feasibility and technique points of laparoscopic
      partial nephrectomy in the treatment of malignant renal tumor. METHODS: 26
      patients with malignant renal tumor underwent partial nephrectomy over the past 5
      years, including 11 cases treated with laparoscopic partial nephrectomy, with the
      mean tumor size of 2.4 cm (1.6 - 4.2 cm), and 15 cases treated with traditional
      open procedure, with the mean tumor size of 2.6 cm (1.8 - 3.1 cm). The surgical
      techniques of the laparoscopic partial nephrectomy included laparoscopic clamp
      control of the renal hilum in order to allow cold knife excision of the mass,
      with laparoscopic repair of the collecting system. The operative time, blood
      loss, warm ischemia time, perioperative complications, fluid intake time, and
      convalescence were evaluated and compared. RESULTS: Laparoscopic procedures were
      successful conducted in the 11 patients without necessity to converse to open
      surgery. The operative time of the traditional open procedure group was (92 +/-
      36) min, significantly shorter than that of the laparoscopic partial nephrectomy
      group [(138 +/- 97) min, P < 0.05]. The mean blood loss of the traditional open
      procedure group was (150 +/- 68) ml, not significantly different from that of the
      laparoscopic partial nephrectomy group [(176 +/- 88) ml, P > 0.05]. The warm
      ischemia time of the laparoscopic partial nephrectomy group was (12 +/- 5) min,
      significantly shorter than that of the traditional open procedure [(25 +/- 18)
      min, P < 0.05]. The fluid intake time after operation of the laparoscopic partial
      nephrectomy group was (16 +/- 6) hours, significantly shorter that of traditional
      open procedure group [(31 +/- 7) hours, P < 0.05]. The post-operative hospital
      stay time of the laparoscopic partial nephrectomy group was (7.0 +/- 2.4) days,
      significantly shorter than that of the traditional open procedure group [(12.0 +/
      4.5) days, P < 0.05]. CONCLUSION: Laparoscopic partial nephrectomy is a feasible
      and safe method for malignant renal tumors. This procedure has the advantages of
      minimal invasion, less complications and shorter convalescence time. In order to
      obtain ideal operative outcome, en bloc control of the renal hilum, cold knife
      excision of the mass, and reliable renal parenchymal repair with suture are
      recommended.

PMID- 18067832
TI  - [Immunotherapy against tumor with dendritic cell sensitized by necrotic tumor
      tissue after microwave coagulation therapy].
AB  - OBJECTIVE: To evaluate if the necrotic tumor tissue treated with microwave
      coagulation therapy (MCT) can sensitize dendritic cell (DCs), and if the
      sensitized DCs have the specific inhibit effect on tumor cell. METHODS: CT-26
      tumor nodules planted percutaneously in BALB/c mice were treated with MCT. The
      treated tumor tissue was levigated and filtrates and the filtrate obtained was
      incubated with the DCs from marrow of the BALB/c mice to get sensitized DCs. The
      shape of the DCs was observed by the microscopy and the electron microscopy
      respectively and the immune phenotype was detected by flow cytometer. The ability
      of the DCs to induce proliferation of T cells was measured by (3)H-TdR
      incorporation assay. The cytotoxicity of CTL activated by the DCs was measured by
      (51)Cr release assay. The inhibition of the DCs on the growth of CT-26 tumor in
      the mice was observed. RESULTS: The DCs cultured with the filter from necrotic
      tissue of CT-26 tumor had the typical shape and immune phenotype of the
      sensitized DCs. The intensity of the sensitized DCs and the naive DC to stimulate
      T lymphocyte proliferation at the DC/T of 1:10 was 80 +/- 10 vs 10 +/- 5 (P <
      0.01); and at the DC/T of 1:20 was 58 +/- 7 vs 9 +/- 3 (P < 0.01). The killing
      effect of specific CTLs on CT-26 cancer cells in the sensitized DCs and the naive
      DCs group were 13.6 +/- 2.5 vs 1.1 +/- 0.4 (P < 0.01) at the E/T of 10:1, 27.5 +/
      4.4 vs 1.4 +/- 0.4 (P < 0.01) at E/T 20:1, and 51.2 +/- 8.1 vs 1.4 +/- 0.5 (P <
      0.01) at the E/T of 50:1 respectively. The specific CTL's killing effect on
      MIP/ND4 lymphoma cells in the sensitized DCs and the naive DCs group were 2.61 +/
      0.64 vs 0.87 +/- 0.15 (P > 0.01) at the E/T of 10:1, 5.22 +/- 0.65 vs 2.18 +/-
      0.41 (P > 0.01)at the E/T of 20:1, and 6.09 +/- 0.83 vs 3.91 +/- 0.51 (P > 0.01)
      at the E/T of 50:1 respectively. The difference of the volumes of the tumor
      implanted percutaneously in the BALB/c mice became more and more obviously with
      the prolongation of mice survival times in the sensitized DC group, the naive DC
      group and the control group. The weight of the tumor at the fortieth day were 4.5
      g +/- 1.1 g, 6.9 g +/- 1.6 g, 9.0 g +/- 1.5 g in the three groups respectively (P
      < 0.01). Finally the special killing effect of the T cells which extracted from
      the spleen of the mice whose tumor had been treated by the sensitized DCs in vivo
      and in vitro were observed. CONCLUSION: As an whole cell antigen, the necrotic CT
      26 tumor tissue treated with MCT can sensitize DCs, and the sensitized DCs have
      the specific inhibitory effect on CT-26 tumor cells both in vivo and in vitro.

PMID- 18067833
TI  - [Treatment of type 1 diabetes by transplantation of bone-derived mesenchymal stem
      cells expressing human insulin gene: experiment with mice].
AB  - OBJECTIVE: To evaluate the effect of treatment of type 1 diabetes by
      transplantation of bone-derived stem cells expressing human insulin gene.
      METHODS: Murine bone marrow-derived stem cells expressing green fluorescent
      protein (GFP-mMSCs) were isolated from 4/6-week-old GFP mice and transfected with
      a recombinant retrovirus-murine stem cell virus (MSCV) encoding human insulin
      gene, thus constructing the GFP-mMSCs-MCV-insulin. 16 C57BL/6J mice were injected
      with streptozotocin so as to establish models of type 1 diabetes and then
      randomly divided into 4 equal groups: Group A, undergoing injection into the
      liver with GFP-mMSC-MCV-insulin 1 week after the establishment of the model,
      Group B, undergoing intrahepatic transplantation of the GFP-mMSCs transfected
      with blank vector, Group C, undergoing intrahepatic transplantation of
      untransfected GFP-mMSCs, and Group D, undergoing intrahepatic transplantation of
      phosphate-buffered saline (PBS). Another 4 normal mice were used as controls and
      underwent intrahepatic transplantation of PBS too. After the transplantation the
      blood glucose, serum insulin, and body weight were detected everyday. 6 weeks
      later immunohistochemistry was used to detect the expression of human insulin in
      the mice liver tissues. RESULTS: The body weight of Group A increased by 6%
      within 6 weeks after treatment, and the average blood glucose level 7 d and 42 d
      after transplantation were (10.4 +/- 2.8) mmol/L and (6.5 +/- 0.9) mmol/L
      respectively, both significantly lower than those of Group D [(26.8 +/- 2.5)
      mmol/L and (25.4 +/- 4.1) mmol/L respectively, both P < 0.05].
      Immunohistochemistry showed secretion of human insulin in serum and liver.
      CONCLUSION: The clinical manifestations of diabetes can be relieved effectively
      by intrahepatic transplantation of mMSCs expressing human insulin gene. This
      study implies a novel approach of gene therapy for type 1 diabetes.

PMID- 18067834
TI  - [C3d enhances immune response to the secreted form of Coxsackie virus B3 VP1 DNA
      vaccine].
AB  - OBJECTIVE: To explore a strategy to enhance the specific immune response induced
      by secreted form of Coxsackie virus B3 (CVB3) capsid protein 1 (sVP1) gene
      vaccination against Coxsackie virus infection. METHODS: Eukaryotic expression
      plasmid pcDNA3/sVP1-C3d3 was constructed by conjugating the 3 copies of C3d
      (C3d3) with the secreted form of sVP1 of CVB3. 42 BALB/c mice were randomly
      divided into 3 equal groups to be inoculated with pcDNA3/sVP1-C3d3, pcDNA3/sVP1
      and pcDNA3 plasmids respectively once every 4 weeks for 3 times. 14 days after
      every inoculation venous blood was collected to measure the titer of neutralizing
      antibody. Three weeks after the last inoculation their spleens were taken out to
      detect the specific CTL cytotoxic activity. Three mice from each group underwent
      intraperitoneal injection of 3 LD(50) CVB3 and were killed 7 days later, and then
      the titer of blood viruses was measured. The remaining 8 mice underwent
      intraperitoneal injection of 5 LD(50) CVB3 and the survival status was observed
      for 21 days. RESULTS: The titer of neutralizing antibody in the mouse blood
      increased along with the time after inoculation. The antibody titer and specific
      CTL cytotoxic activity 3 days after inoculation of the pcDNA3/sVP1-C3d3 group
      were 33.6 +/- 1.7 and 66.1% +/- 2.9% respectively, both significantly stronger
      than those of the pcDNA3/sVP1 group [(28.3 +/- 1.7) and (52.8% +/- 3.3%)
      respectively, both P < 0.05]. After lethal CVB3 challenge, the blood virus titer
      of the pcDNA3/sVP1-C3d3 group was significantly lower than that of the pcDNA3
      group (P < 0.05), and the survival rate of pcDNA3/sVP1-C3d3 group was 50%,
      significantly higher than that of the pcDNA3 group (0, P < 0.05), however, not
      significantly different from that of the pcDNA3/sVP1 group (25%, P > 0.05).
      CONCLUSION: C3d strongly enhances the specific immune response induced by SVP1
      gene vaccination.

PMID- 18067835
TI  - [Influence of cyclosporine A on the mRNA and protein expression of major
      histocompatibility complexes I and II: experiment with rabbits].
AB  - OBJECTIVE: To investigate the influence of cyclosporine A (CsA) on the mRNA and
      protein expression of major histocompatibility (MHC) I and II. METHODS: 14 New
      Zealand white rabbits were randomly divided into three groups to be injected
      intramuscularly 5 mg/kg once a day for 30 days (low dose CsA group, n = 5), 20
      mg/kg (high dose CsA group, n = 5), or normal saline (control group, n = 4).
      Peripheral blood sample was collected every 5 days, monouclear cells were
      isolated, total RNA was extracted, and 30 days later the rabbits were killed and
      their livers, spleens, kidneys, and thyroid glands were taken out, total RNA was
      extracted, RT-PCR and Western blotting were used to examine the mRNA and protein
      expression of MHCI and MHCII. RESULTS: The peripheral blood monouclear cell MHCI
      and MHCII mRNA expression levels on day 10 of the low dose CsA group were 1.78 +/
      0.15 and 7.30 +/- 0.51, both significantly higher than those before the
      injection of CsA (0.23 +/- 0.04 and 2.77 +/- 0.25, both P < 0.01); the MHCI and
      MHCII protein expression levels were 11.32 +/- 1.45 and 22.31 +/- 1.91, both
      significantly higher than those before the injection (2.31 +/- 0.14 and 12.52 +/-
      1.23, both P < 0.01). In high dose CsA group, the MHCI and MHCII mRNA expression
      levels on day 10 were 4.72 +/- 0.28 and 14.20 +/- 2.58, both significantly higher
      than those before the injection (0.24 +/- 0.06 and 2.56 +/- 0.33, both P < 0.01);
      the protein expression levels were 13.81 +/- 1.38 and 24.22 +/- 2.88, both
      significantly higher than those before the injection (2.42 +/- 0.06 and 12.51 +/-
      1.31, both P < 0.01). Since the day 15, the levels of MHCI and MHCII mRNA and
      protein expression levels began decrease gradually until the levels before the
      injection. By the end of the experiment there was no significant difference in
      the MHCI and MHCII mRNA and protein expression levels of the liver, spleen,
      kidney, and thymus among the 3 groups. CONCLUSION: Cyclosporine can increase the
      host MHCI and MHCII expression for a period of time.

PMID- 18067836
TI  - [Construction of a recombinant Pim3-expressing plasmid and expression and
      activity thereof: experiment with rats].
AB  - OBJECTIVE: To construct a plasmid expressing green fluorescent protein (GFP) and
      gene of Pim-3, a member of the serine/threonine kinase family, and to investigate
      the in vivo expression of the construct and its effect on cell apoptosis.
      METHODS: Pim-3 gene was cloned from myocardium tissues of Wistar rat by RT-PCR
      and subcloned into GFP-expressing plasmid vector pEGFP-N2 by restriction enzyme.
      The recombinant plasmid pEGFP-N2/Pim-3 was constructed by T4-ligase and then
      identified through enzyme digestion and gene sequencing. Thirty-two Wistar rats
      were randomly divided into 4 equal groups: Group A, as control group; Group B,
      injected intravenously with Ringer's solution; Group C, injected with blank
      vector, and Group D, injected with the recombinant plasmid pEGFP-N2/Pim-3. One
      day later, endotoxin/D-galactoamine (D-GalN) was intraperitoneally injected. 24
      hours later the rats were killed. Fluorescence microscopy was used to observe the
      expression of the reporter gene GFP in the liver tissues. RT-PCR was used to
      detect the Pim-3 mRNA expression. The hepatic apoptosis was detected by TUNEL
      assay. The activity of caspase-3 was detected. RESULTS: A 998 bp target cDNA
      fragment with restriction enzyme sites was amplified and inserted into the
      multiple clone site of pEGFP-N2 successfully. High expression levels of the
      target gene Pim-3 and reporter gene GFP were achieved in the rat liver after
      transfer of the recombinant plasmid. The relative Pim-3 expression level of Group
      D was 0.49 +/- 0.15, significantly higher than those of Groups A, B, and C (0.06
      +/- 0.02, 0, and 0 respectively, all P < 0.01). The apoptotic index of Group D
      was (4.9 +/- 1.2)%, significantly lower than those of Groups B and C [(72.5 +/-
      6.1)% and (69.8 +/- 5.7)% respectively, both P < 0.01]; however, not
      significantly different from that of Group A [(3.1 +/- 0.7)%]. The activity of
      caspase-3 of Group D was (76 +/- 27) pmol.min(-1).mg(-1), significantly lower
      than those of Groups B and C [(147 +/- 55) and (142 +/- 50) pmol.min(-1).mg(-1),
      respectively, both P < 0.01]; however, not significantly different from that of
      Group A (60 +/- 15). CONCLUSION: The recombinant plasmid pEGFP-N2/Pim-3 can
      achieve high expression in living cells and have an inhibitory effect on hepatic
      apoptosis.

PMID- 18067838
TI  - [Dexamethasone up-regulates the expression of glucocorticoid receptor in growth
      plate and inhibits the longitudinal growth of bone: experiment with rats].
AB  - OBJECTIVE: To investigate the regulation of the glucocorticoid of pharmacological
      doses on the expression of glucocorticoid receptor in growth plate and to explore
      the mechanism of the direct inhibition of the longitudinal growth of bone by
      dexamethasone. METHODS: Twenty 3-week-old male weanling SD rats were randomly
      divided into two groups: dexamethasone group (n = 12), intraperitoneally injected
      with dexamethasone 200 microg/100 g body weight once a day for 10 days and
      control group (n = 8), intraperitoneally injected with normal saline of the same
      volume. Ten days later the rats were killed. The length of the proximal tibia was
      excised, fixed and decalcified, and then paraffin embedded. Sections of 5 microm
      thick were cut and processed for histomorphometry The total height of growth
      plate, height of proliferative zone, and height of hypertrophic zone were
      determined. RESULTS: The length of tibia, total height of growth plate, height of
      proliferative zone, and height of hypertrophic zone of the dexamethasone group
      were 28.9 mm +/- 1.2 mm, 4.01 microm +/- 0.28 microm, 1.98 microm +/- 0.13
      microm, and 1.67 microm +/- 0.18 microm respectively, all significantly lower
      those of the control group (30.5 mm +/- 1.1 mm, 5.53 microm +/- 0.46 microm, 2.25
      microm +/- 0.30 microm, and 2.87 microm +/- 0.19 microm respectively, all P <
      0.01). The resting chondrocytes and hypertrophic chondrocytes in the growth
      plates of the rats in the dexamethasone group all expressed glucocorticoid
      receptor, whereas the proliferating chondrocytes didn't. The absorbance values of
      the resting chondrocytes and hypertrophic chondrocytes in the growth plates of
      the dexamethasone group were 0.238 +/- 0.026 and 0.283 +/- 0.042 respectively,
      both significantly higher than those of the control group (0.187 +/- 0.027 and
      0.211 +/- 0.022 respectively, both P < 0.01). CONCLUSION: The glucocorticoid
      receptors are essential for the longitudinal growth of bone. The glucocorticoid
      of pharmacological dose inhibits the longitudinal growth of bone by up-regulating
      the expression of glucocorticoid receptor.

PMID- 18067837
TI  - [Expression of acylation stimulating protein receptor (C5L2) in preadipocytes
      during differentiation and under stimulation of free fatty acids].
AB  - OBJECTIVE: To observe the changes of expression of the acylation stimulating
      protein (ASP) functional receptor C5L2 during adipocytes differentiation, and to
      study the regulation of C5L2 by free fatty acid (FFA) in cultured adipocytes and
      preadipocytes. METHODS: Preadipocytes of the line 3T3-L1 were cultured and
      induced to differentiate. Oleate or palmitate of the doses 0 - 1.0 mmol/L were
      added into the cultured fluid of the 3T3-L1 mature adipocytes or preadipocytes
      overnight. RT-PCR and flow cytometry were used to detect the mRNA and protein
      expression of C5L2. RESULTS: The C5L2 mRNA expression level of the adipocytes 9
      days after differentiation was 0.89 +/- 0.24, 3.56 times that before induction
      (0.25 +/- 0.12, P < 0.01). The C5L2 protein expression 6 h after induction was
      61% +/- 18%, higher by 21% in comparison of that at the 0 d (51% +/- 15%, P <
      0.05), and the C5L2 protein expression 12 h after induction reached a maximal
      level (70% +/- 12%), 38% higher than that at 0 d (P < 0.01). Then the C5L2
      protein expression decreased significantly on the third day after induction to
      the level on the day 0. The C5L2 mRNA expression levels of the mature adipocytes
      stimulated by oleate 0.125, 0.5, and 1.0 mmol/L for 18 h were decreased by 6%,
      46%, and 84% respectively compared with that of the oleate 0 mmol/L (all P <
      0.05); however, the C5L2 mRNA expression levels of the preadipocytes stimulated
      by oleate 0.125, 0.5, and 1.0 mmol/L for 18 h were not significantly different
      from that of the oleate 0 mmol/L group. The C5L2 mRNA expression levels of the
      mature adipocytes stimulated by palmitate 0.125, 0.5, and 1.0 mmol/L for 18 h
      were decreased suppressed dose-dependently, for example, the C5L2 mRNA expression
      level of the palmitate 1.0 mmol/L group was lower than that of the palmitate 1.0
      mmol/L group by 41% (P < 0.05); however, the C5L2 mRNA expression levels of the
      palmitate 1.0 mmol/L group was not significantly different from that of the
      palmitate 0 mmol/L group. CONCLUSION: The ASP/C5L2 pathway plays a role in
      adipocytes differentiation. Downregulation of C5L2 mRNA and protein may
      contribute to impaired insulin.

PMID- 18067839
TI  - [Effect analysis of modified radical surgery in tongue cancer at early stages].
AB  - OBJECTIVE: To evaluate the oncologic efficacy, surgical safety, postoperative
      beauty, and morbidity of an ideal procedure of modified radical surgery in tongue
      cancer at early stages. METHODS: Six patients with early stage squamous cell
      carcinoma of tongue underwent a procedure of modified radical surgery, in which
      an inconspicuous incision was used, the external jugular vein,
      sternocleidomastoid muscle, spino-accessory nerve, and greater auricular nerve
      were preserved, half of glosso and mouth floor were excised, and the defect was
      repaired instantly. Recurrence of glosso, mouth floor and neck, regional edema,
      shoulder dysfunction, auricle sensibility, oral cavity function and beautiful
      outlook on the face and neck were evaluated clinically. RESULTS: Compared with
      classic radical neck dissection, this procedure of modified radical surgery
      showed an inconspicuous incision and pretty appearance, minor edema on face and
      neck, better shoulder function, and sensation of auricular skin. No recurred to
      the glosso, mouth floor, and neck was found during follow-up. The patients showed
      better oncological safety, pretty appearance of tongue, and better oral function
      of speech, swallow and mastication. CONCLUSION: This ideal procedure of modified
      radical surgery in tongue cancer at early stages lessens or avoids destruction of
      face and neck, shoulder malfunction, numbness of auricular skin, and oral
      dysfunction of speech, swallow and mastication without impairment on the
      oncologic safety of the radical surgery, and improves the quality of life of the
      patients.

PMID- 18067847
TI  - H5N1 in wild and domestic birds in Europe--remaining vigilant in response to an
      ongoing public health threat.

PMID- 18067848
TI  - Contact tracing of passengers exposed to an extensively drug-resistant
      tuberculosis case during an air flight from Beirut to Paris, October 2006.

PMID- 18067849
TI  - Guidelines for laboratory diagnosis of Neisseria gonorrhoeae infections in
      Eastern European countries--results of an international collaboration.

PMID- 18067851
TI  - The proximal region of a noncatalytic eukaryotic seryl-tRNA synthetase extension
      is required for protein stability in vitro and in vivo.
AB  - Eukaryotic cytosolic seryl-tRNA synthetases (SerRS) have idiosyncratic C-terminal
      extensions not present in prokaryotic counterparts. The extensions of two
      eukaryotic SerRSs were subjected to mutagenesis and partial truncation. Only
      minor parts of the yeast or maize SerRS extensions, adjacent to the catalytic
      core (7 of 20 and 8 of 26 amino acids, respectively), were found to be
      indispensable for protein stability. Truncated proteins with substantially
      shortened extensions displayed unaltered catalytic properties and could
      complement a Saccharomyces cerevisiae strain with a disrupted SerRS gene, if
      these proximal regions were left intact. Although the yeast C-terminal SerRS
      extension is required for Pex21p binding, the maize counterpart with an appended
      yeast SerRS extension remained incapable of Pex21p binding, implying that
      additional regions of yeast SerRS may also contribute to the interaction with the
      peroxin. The proximal region of the eukaryotic SerRS C-terminal extension is
      indispensable for protein stability, while the remaining part of the extension
      remains available for other functions, such as species-specific protein:protein
      interactions.

PMID- 18067852
TI  - Responding double-porous lipid membrane: lyotropic phases in a polymer scaffold.
AB  - The large osmotic gradient over the outermost layer of human skin implies major
      structural changes along the gradient, which in turn affects transport. In
      particular, the possibility of phase changes introduces a non-linear element to
      the transport behaviour. We present a novel model membrane system to be used for
      studying these transport mechanisms, where we use a hydrophobic porous polymer
      membrane as a scaffold for lipid lyotropic phases. The polymer membrane provides
      mechanical robustness, but also prevents defects of the lipid lyotropic phases,
      and it can induce an orientation of anisotropic phases. We study the location,
      structure and phase behaviour of the confined phases. It is shown that this model
      membrane system allow for accurate measurements of transport through lipid
      membranes in the presence of different osmotic gradients. A theoretical
      description is evaluated and shows that this phenomenon can be understood in
      terms of the proposed mechanism of phase changes. The novel double-porous lipid
      membrane constitutes a mechanically robust system for studies in aligned systems,
      which is generally very difficult to achieve. This could have large implications
      for studies of transport processes in, e.g. skin and other biomembrane model
      systems.

PMID- 18067853
TI  - FGF-2 signaling induces downregulation of TAZ protein in osteoblastic MC3T3-E1
      cells.
AB  - Transcriptional coactivator with PDZ-binding motif (TAZ) protein is a coactivator
      of Runx2 and corepressor of PPARgamma. It also induces differentiation of
      mesenchymal cells into osteoblasts. In this study, we found that FGF-2, which
      inhibits bone mineralization and stimulates cell proliferation, reduced the TAZ
      protein expression level in osteoblast-like cells, MC3T3-E1. This reduction was
      recovered by removing FGF-2 from the culture medium, which also restored the
      osteoblastic features of MC3T3-E1 cells. Furthermore, FGF-2-induced reduction of
      TAZ is blocked by a SAPK/JNK-specific inhibitor. These findings suggest that the
      expression of TAZ protein is involved in osteoblast proliferation and
      differentiation. This may help elucidate the discrepancies in the effect of FGF-2
      and contribute to the understanding of FGF/FGFR-associated craniosynostosis
      syndrome etiology and treatment.

PMID- 18067854
TI  - A period of convergence in the studies on muscle contraction and relaxation: the
      Ebashi's contribution.
AB  - The object of this paper is to trace the growth of a fundamental problem that for
      a decade hindered the development of several lines of muscle research: the
      molecular mechanism that allows and controls contraction and relaxation of muscle
      fiber. Emphasis is placed on the difficulties to be overcome; thus the paper
      records not only the achievements and successes, but also the unavoidable failure
      and disappointments. The account highlights the essential contribution of Setsuro
      Ebashi to find the solution of the problem.

PMID- 18067855
TI  - Chloride ions control the G1/S cell-cycle checkpoint by regulating the expression
      of p21 through a p53-independent pathway in human gastric cancer cells.
AB  - The aim of the present study is to investigate whether the chloride affects cell
      growth and cell-cycle progression of cancer cells. In human gastric cancer MKN28
      cells, the culture in the Cl(-)-replaced medium (replacement of Cl(-) by NO(3)(
      )) decreased the intracellular chloride concentration ([Cl(-)](i)) and inhibited
      cell growth. The inhibition of cell growth was due to cell-cycle arrest at the
      G(0)/G(1) phase caused by diminution of CDK2 and phosphorylated Rb. The culture
      of cells in the Cl(-)-replaced medium significantly increased expressions of p21
      mRNA and protein without any effects on p53. These observations indicate that
      chloride ions play important roles in cell-cycle progression by regulating the
      expression of p21 through a p53-independent pathway in human gastric cancer
      cells, leading to a novel, unique therapeutic strategy for gastric cancer
      treatment via control of [Cl(-)](i).

PMID- 18067856
TI  - Influenza PR8 HA-specific Fab fragments produced by phage display methods.
AB  - Anti-influenza hemagglutinin (HA) Fabs were isolated from a phage display library
      using purified HA of influenza virus A/Puerto Rico/8/34 (PR8; H1N1) as an
      antigen. Four Fab clones displaying a 25-50-fold higher binding signal to PR8 HA
      than the control were selected for further analysis and comparison with anti-PR8
      monoclonal antibody (mAb). All four Fabs and mAb recognized the PR8 HA under non
      reducing conditions but rarely bound to reduced PR8 HA. Inhibition of influenza
      virus infection on MDCK cells was observed with Fab1 and mAb in a dose-dependent
      manner while Fab3 and 4 exhibited only a partial inhibitory effect. Moreover,
      Fab1 clone and mAb exhibited cross-reactivity with the A/Peking/262/95 (A/Peking;
      H1N1) strain. The inhibitory effects of mAb on both influenza strains were more
      potent than Fab1, which is likely attributed to its higher affinity for the
      antigen. SPR analyses, in fact, revealed that Fab1 and mAb have K(D) of 1.5 x 10(
      8) and 3.2 x 10(-9)M, respectively. These results strongly suggest that phage
      library-derived Fabs can be readily prepared and that such HA-specific Fabs with
      inhibitory action on influenza infection may be used to treat influenza patients.

PMID- 18067857
TI  - Femtosecond spectroscopy probes the folding quality of antibody fragments
      expressed as GFP fusions in the cytoplasm.
AB  - Time-resolved femtosecond spectroscopy can improve the application of green
      fluorescent proteins (GFPs) as protein-folding reporters. The study of ultrafast
      excited-state dynamics (ESD) of GFP fused to single chain variable fragment
      (scFv) antibody fragments, allowed us to define and measure an empirical
      parameter that only depends on the folding quality (FQ) of the fusion. This
      method has been applied to the analysis of genetic fusions expressed in the
      bacterial cytoplasm and allowed us to distinguish folded and thus functional
      antibody fragments (high FQ) with respect to misfolded antibody fragments.
      Moreover, these findings were strongly correlated to the behavior of the same
      scFvs expressed in animal cells. This method is based on the sensitivity of the
      ESD to the modifications in the tertiary structure of the GFP induced by the
      aggregation state of the fusion partner. This approach may be applicable to the
      study of the FQ of polypeptides over-expressed under reducing conditions.

PMID- 18067858
TI  - Distinct mechanisms for dysfunctions of mutated ryanodine receptor isoforms.
AB  - Ryanodine receptor (RyR) is the Ca(2+)-induced Ca(2+) release channel in cells.
      RyR1 and RyR2 are its isoforms expressed in the skeletal and cardiac muscles,
      respectively. Their missense mutations, which are clustered in three regions that
      correspond to each other, cause hereditary disorders such as malignant
      hyperthermia and central core disease in skeletal muscle and catecholaminergic
      polymorphic ventricular tachycardia in cardiac muscle. Their pathogeneses,
      however, are not well understood. The following hypotheses are favorably
      discussed in this article: phenotypes with RyR1 and RyR2 mutations are mainly
      caused by dysregulations of their functions through the interdomain interaction
      and luminal Ca(2+), respectively.

PMID- 18067859
TI  - Functional requirement of CCN2 for intramembranous bone formation in embryonic
      mice.
AB  - CCN2 is best known as a promoter of chondrocyte differentiation among the CCN
      family members, and Ccn2 null mutant mice display skeletal dysmorphisms. However,
      little is known concerning the roles of CCN2 during bone formation. We herein
      present a comparative analysis of wild-type and Ccn2 null mice to investigate the
      roles of CCN2 in bone development. Multiple histochemical methods were employed
      to analyze the effects of CCN2 deletion in vivo, and effects of CCN2 on the
      osteogenic response were evaluated with the isolated and cultured osteoblasts. As
      a result, we found a drastic reduction of the osteoblastic phenotype in Ccn2 null
      mutants. Importantly, addition of exogenous CCN2 promoted every step of
      osteoblast differentiation and rescued the attenuated activities of the Ccn2 null
      osteoblasts. These results suggest that CCN2 is required not only for the
      regulation of cartilage and subsequent events, but also for the normal
      intramembranous bone development.

PMID- 18067860
TI  - Novel mutations of NP in two patients with purine nucleoside phosphorylase
      deficiency.

PMID- 18067861
TI  - Baseline serum matrix metalloproteinase-9 level predicts long-term prognosis
      after coronary revascularizations in stable coronary artery disease.
AB  - OBJECTIVES: This study aimed to investigate whether baseline serum levels of
      matrix metalloproteinases (MMPs) could predict long-term prognosis of coronary
      revascularizations. DESIGNS AND METHODS: Ninety-one consecutive patients
      receiving coronary revascularizations (58 percutaneous coronary interventions and
      33 coronary artery bypass graft surgeries) for stable coronary artery disease
      (CAD) were studied. Baseline serum levels of high-sensitive C-reactive protein
      (hsCRP), MMP-2, -3 and -9 drawn before revascularization were correlated to the
      clinical adverse events within >12 months after revascularizations. RESULTS:
      Baseline characteristics were similar between the two groups. There were total 22
      major adverse cardiovascular events during a mean period of 27 months. Only
      baseline serum MMP-9 level independently predicted future cardiovascular events
      after coronary revascularization either by multivariate analysis (relative risk
      3.18, p=0.028) or by Kaplan-Meier analysis (p=0.021). CONCLUSIONS: Baseline serum
      MMP-9 level predicted the prognosis after coronary revascularizations, suggesting
      its potential role in risk stratification before revascularization strategies for
      stable CAD.

PMID- 18067862
TI  - Activation of prothrombin by ASP, a serine protease released from Aeromonas
      sobria.
AB  - The effect of a serine protease (ASP) secreted from Aeromonas sobria on plasma
      coagulation was investigated. Proteolytically active ASP promoted human plasma
      coagulation in a dose-dependent manner. Consistent with the preference for a
      factor Xa-specific oligo-peptide substrate, ASP produced enzymatic activity from
      human prothrombin but not from factors IX and X. ASP cleaved prothrombin to
      produce enzymatically active 37 kDa-fragment displaying the same molecular mass
      as alpha-thrombin. ASP is the first bacterial serine protease that produces alpha
      thrombin, through which ASP may contribute to the induction of thrombotic
      tendency in disseminated intravascular coagulation complicated with sepsis caused
      by A. sobria infections.

PMID- 18067863
TI  - Chemical DNA damage activates p21 WAF1/CIP1-dependent intra-S checkpoint.
AB  - When cells progressing in G(1) phase are irradiated with UV light, two damage
      checkpoint pathways are activated: CHK1-Cdc25A and p53-p21WAF1/CIP1, both
      targeting Cdk2 but the latter inducing long lasting inactivation. In similarly
      irradiated S phase cells, however, p21WAF1/CIP1-dependent checkpoint is largely
      inactive. We report here that p21-dependent checkpoint can effectively be
      activated and induce a prolonged S phase arrest with similarly extended
      inactivation of Cdk2 by association of p21 if mid-S phase cells are damaged with
      a base-modifying agent instead of UV light, indicating that the poor utilization
      of p21-dependent checkpoint is not an innate property of S phase cells.

PMID- 18067864
TI  - Phorbol myristate acetate-induced Egr-1 expression is suppressed by phospholipase
      D isozymes in human glioma cells.
AB  - Early growth response-1 (Egr-1) is involved in the regulation of cell growth.
      Here, we found that overexpression of phospholipase D (PLD) isozymes decreased
      tumor promoter phorbol myristate acetate (PMA)-induced Egr-1 expression and
      transactivation in glioma cells. Suppression of PMA-induced Egr-1 was dependent
      on the expression level of PLD isozymes. Overexpression of catalytically inactive
      PLD, treatment with PA, and prevention of PA dephosphorylation by 1-propranolol
      significantly suppressed PMA-induced Egr-1 expression. PLD-induced suppression of
      Egr-1 was reversed by inhibition of phosphatidylinositol 3-kinase (PI3K). Taken
      together, these results suggest that elevated expression and activity of PLD
      attenuate PMA-induced Egr-1 expression via PI3K pathway.

PMID- 18067865
TI  - Gene expression profiling of mammary glands of cathepsin E-deficient mice
      compared with wild-type littermates.
AB  - Cathepsin E is an endolysosomal aspartic proteinase predominantly expressed in
      cells of the immune system and has been implicated in various physiological and
      pathological processes. Because of physiological substrates of cathepsin E have
      not yet been identified, however, the physiological significance of this protein
      still remains speculative. To better understand the physiological significance of
      cathepsin E in the mammary gland, we investigated the effect of the deficiency of
      this protein on the gene expression profile of the tissue. Here we used mammary
      glands derived from multiparous and non-pregnant 11-month-old syngenic wild-type
      (CatE(+/+)) and cathepsin E-deficient (CatE(-/-)) mice for extraction of total
      RNA from each tissue and subsequent mRNA amplification, DNA fragmentation, and
      hybridization with cDNA mixroarray chips. A total of 654 genes were identified as
      overexpressed (>2-fold) in CatE(-/-) mammary glands compared with CatE(+/+)
      counterparts. These included genes related to signal transduction, immune
      responses, growth factor activity, and milk proteins, which occupied a large
      portion of the gene fragments identified as overexpressed. In contrast, a total
      of 665 known genes were identified as underexpressed in the mammary gland of
      CatE(-/-) mice compared with CatE(+/+) counterparts. These included genes related
      to cytoskeleton, cell differentiation, cell cycle arrest and apoptosis, which
      occupied the majority of the gene fragments identified as underexpressed. The
      results thus suggest that cathepsin E in mammary glands plays a crucial role in
      the regulation of proteins involved in signaling, development, differentiation
      and proliferation in the mammary gland.

PMID- 18067866
TI  - Exploring an alignment free approach for protein classification and structural
      class prediction.
AB  - Alignment free methods based on Chaos Game Representation (CGR), also known as
      sequence signature approaches, have proven of great interest for DNA sequence
      analysis. Indeed, they have been successfully applied for sequence comparison,
      phylogeny, detection of horizontal transfers or extraction of representative
      motifs in regulation sequences. Transposing such methods to proteins poses
      several fundamental questions related to representation space dimensionality.
      Several studies have tackled these points, but none has, so far, brought the
      application of CGRs to proteins to their fully expected potential. Yet, several
      studies have shown that techniques based on n-peptide frequencies can be relevant
      for proteins. Here, we investigate the effectiveness of a strategy based on the
      CGR approach using a fixed reverse encoding of amino acids into nucleic
      sequences. We first explore its relevance to protein classification into
      functional families. We then attempt to apply it to the prediction of protein
      structural classes. Our results suggest that the reverse encoding approach could
      be relevant in both cases. We show that it is able to classify functional
      families of proteins by extracting signatures close to the ProSite patterns.
      Applied to structural classification, the approach reaches scores of correct
      classification close to 84%, i.e. close to the scores of related methods in the
      field. Various optimizations of the approach are still possible, which open the
      door for future applications.

PMID- 18067867
TI  - Localization of post-proline cleaving peptidases in Tenebrio molitor larval
      midgut.
AB  - Two soluble post-proline cleaving peptidase activities, PPCP1 and PPCP2, were
      demonstrated in Tenebrio molitor larval midgut with the substrate
      benzyloxycarbonyl-L-alanyl-L-proline p-nitroanilide. Both activities were serine
      peptidases. PPCP1 was active in acidic buffers, with maximum activity at pH 5.3,
      and was located mainly in the more acidic anterior midgut lumen. The dynamics of
      PPCP1 activity and the total activity of soluble digestive peptidases in the
      course of food digestion were similar, suggesting that the enzyme participates in
      protein digestion. PPCP2 is a nondigestive soluble tissue enzyme evenly
      distributed along the midgut. An increase in the activity of PPCP2 was observed
      in buffers of pH 5.6-8.6 and was maximal at pH 7.4. The sensitivity of PPCP2 to
      inhibitors and the effect of pH are similar to prolyl oligopeptidases with a
      cysteine residue near the substrate binding site.

PMID- 18067868
TI  - Improved activity of enzymes in mixed cationic reverse micelles with imidazolium
      based surfactants.
AB  - This work reports the significant enhancement in performance of interfacially
      active enzymes, Chromobacterium viscosum (CV) lipase and horseradish peroxidase
      (HRP) in mixed reverse micelles of cetyltrimethylammonium bromide (CTAB) and
      imidazolium-based amphiphiles having varying tail lengths. Lipase activity in
      these mixed systems was always higher than that in the individual cationic
      reverse micelles of CTAB or any imidazolium surfactant, highest being observed in
      the mixed system of CTAB (50 mM) and 6 (1-tetradecyl-3-methyl imidazolium
      bromide, 40 mM)/water/isooctane/n-hexanol (0.24 M), second-order rate constant,
      k2=1301+/-5 cm3 g(-1)s(-1), approximately 200% higher compared to that in CTAB
      and approximately 65% more than the most popular AOT-microemulsion. Activity
      increased with concentration of imidazolium surfactant and also with its alkyl
      tail length. To have a more profound view on the structure-activity relationship,
      CTAB was replaced by cetyltriethylammonium bromide (CTEAB) and
      cetyltripropylammonium bromide (CTPAB) with subsequent increase in the headgroup
      size. The generalized influence of these mixed cationic systems on surface-active
      enzyme was also verified using HRP, where the activity improved approximately
      100%. This enhancement in enzyme activity is presumably due to the activating
      effect of the imidazolium cation in the enzymatic reactions by improving the
      nucleophilicity of interfacial water in vicinity of enzyme through hydrogen
      bonding.

PMID- 18067869
TI  - Reduction of paraquat-induced renal cytotoxicity by manganese and copper
      complexes of EGTA and EHPG.
AB  - Superoxide anion generation plays an important role in the development of
      paraquat toxicity. Although superoxide dismutase mimetics (SODm) have provided
      protection against organ injury involving generation of superoxide anions, they
      often suffer problems, e.g., regarding their bioavailability or potential pro
      oxidant activity. The aim here was to investigate and compare the therapeutic
      potential of two novel SODm, manganese(II) and copper(II) complexes of the
      calcium chelator ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA) and of
      the contrast agent ethylenebis(hydroxyphenylglycine) (EHPG), against paraquat
      induced renal toxicity in vitro. Incubation of renal NRK-52E cells with paraquat
      (1 mM) for 24 h produced submaximal, yet significant, reduction in cellular
      viability and cell death and produced significant increases in superoxide anion
      and hydroxyl radical generation. Manganese and copper complexes of EGTA (10-100
      microM) and EHPG (30-100 microM) reduced paraquat-induced renal cell toxicity and
      reduced superoxide anion and hydroxyl radical generation significantly. Manganese
      complexes displayed greater efficacy than copper complexes and, at equivalent
      concentrations, manganese complexed with EHPG provided the greatest protection.
      Furthermore, these metal complexes did not interfere with the uptake of [methyl
      (14)C]paraquat into NRK-52E cells, suggesting that they provided protection
      against paraquat cytotoxicity via intracellular mechanisms. These complexes did
      not display cytotoxicity at the concentrations examined. Together, these results
      suggest that manganese and copper complexes of EGTA and EHPG, and especially the
      manganese-EHPG complex, could provide benefit against paraquat nephrotoxicity.

PMID- 18067870
TI  - Inhibition of heme protein redox cycling: reduction of ferryl heme by iron
      chelators and the role of a novel through-protein electron transfer pathway.

PMID- 18067871
TI  - Conserved spatial patterns across the protein kinase family.
AB  - Protein kinases are a large family of enzymes heavily involved in signal
      transduction, regulation of metabolism, and control of cell growth and
      differentiation. These functions require precise recognition of widely diverse
      signals and substrates, and very detailed control of protein kinase activity.
      Large molecules interact primarily through recognition of surface features.
      Comparison of surfaces is complicated by both sequence diversity and
      conformational variability, including multiple possible rotameric states of side
      chains. We used a recently developed method of protein surface comparison to
      compare different serine/threonine and tyrosine kinases. As we have shown, two
      hydrophobic cores inside a protein kinase molecule are connected by a unique
      formation, called the "spine". It exists only in the active conformation of
      protein kinases and is dynamically disassembled during the inactivation process.
      Detection of such structures by any other method was not possible as the residues
      which comprise the spine do not form any sequence or 3D motifs in a traditional
      sense.

PMID- 18067872
TI  - Lipase specificity towards eicosapentaenoic acid and docosahexaenoic acid depends
      on substrate structure.
AB  - The fatty acid specificity of five lipases towards eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA) was evaluated in the hydrolysis of fish oil, squid
      oil and a model system. The model system contained methyl esters of EPA, DHA and
      palmitic acid. All the investigated lipases discriminated against both EPA and
      DHA more in the model system than in the natural oils. Thus both EPA and DHA were
      more easily hydrolysed from a glyceride than from a methyl ester. In the model
      system, the lipase from Candida rugosa showed the highest discrimination against
      DHA, while the lipases from Pseudomonas fluorescens and Pseudomonas cepacia
      discriminated against EPA the most. In a glyceride, the fatty acid specificity of
      lipases towards EPA and DHA was affected by the positional distribution of the
      fatty acids and the glyceride structure due to the regiospecificity and
      triglyceride specificity of the lipase. In the oils, the Pseudomonas lipases also
      discriminated against EPA the most, while DHA was initially discriminated the
      most by the lipase from Thermomyces lanuginosus. However, after longer reaction
      times the enrichment of DHA in the glyceride fraction of the oils was greatest
      for the lipase from C. rugosa.

PMID- 18067873
TI  - Crystal structure of a protein, structurally related to glycosyltransferases,
      encoded in the Rhodobacter blasticus atp operon.
AB  - The F1-ATP synthase atp operon in the proteobacterium Rhodobacter blasticus
      contains six open reading frames, encoding six hypothetical proteins. Five of
      these subunits, in the stoichiometry (alphabeta)3gamma delta epsilon make up the
      catalytic F1-ATP synthase complex similarly in bacteria, chloroplasts and
      mitochondria. The sixth gene of the R. blasticus atp operon, urf6, shows very
      little sequence homology to any protein of known structure or function. The gene
      has previously been cloned, the product (called majastridin) has been
      heterologously expressed in Escherichia coli, and purified to high homogeneity
      [M. Brosche, I. Kalbina, M. Arnfelt, G. Benito, B.G. Karlsson, A. Strid,
      Occurrence, overexpression and partial purification of the protein (majastridin)
      corresponding to the URF6 gene of the Rhodobacter blasticus atp operon, Eur. J.
      Biochem. 255 (1998) 87-92]. We have solved the X-ray crystal structure and
      refined a model of majastridin to atomic resolution. Here we present the crystal
      structures of apo-majastridin and the complex of majastridin with Mn2+ and UDP
      and show that it has extensive structural similarity to glycosyltransferases (EC
      2.4). This is the first structure determined from a new group of distantly
      related bacterial proteins of at least six members. They share the identical
      amino acids that bind Mn2+ and a triplet of amino acids in the putative sugar
      binding site.

PMID- 18067874
TI  - Purified trout egg vitelline envelope proteins VEbeta and VEgamma polymerize into
      homomeric fibrils from dimers in vitro.
AB  - The rainbow trout egg vitelline envelope (VE) is composed of three proteins,
      called VEalpha ( approximately 58-60kDa Mr), VEbeta ( approximately 52kDa Mr),
      and VEgamma ( approximately 47kDa Mr). Each of these proteins is related to mouse
      egg zona pellucida (ZP) glycoproteins, called ZP1, ZP2, and ZP3, and possesses a
      ZP domain that has been implicated in the polymerization of the proteins into
      long, interconnected fibrils or filaments. Here, trout egg VEbeta and VEgamma
      were purified to homogeneity and analyzed under various experimental conditions
      (SDS-PAGE, Blue Native-(BN-)PAGE, size-exclusion chromatography, and transmission
      electron microscopy) to determine whether individual VE proteins would polymerize
      into fibrils in vitro. Such analyses revealed that in the presence of 6M urea
      each VE protein is present primarily as monomers and as small oligomers (dimers,
      tetramers, etc.). However, either a reduction in urea concentration or a complete
      removal of urea results in the polymerization of VEbeta and VEgamma dimers into
      very large oligomers. Mixtures of VEbeta and VEgamma also give rise to large
      oligomers. Under these conditions, VE proteins are visualized by transmission
      electron microscopy as aggregates of long fibrils, with each fibril composed of
      contiguous beads located periodically along the fibril. The relationship between
      the behavior of fish egg VE proteins and mouse ZP glycoproteins, as well as other
      ZP domain-containing proteins, is discussed.

PMID- 18067875
TI  - Specific and non-specific mammalian RNA terminal uridylyl transferases.
AB  - Uridylylation of various types of RNA molecules is a wide-spread phenomenon in
      molecular biology and is catalyzed by enzymes mediating the transfer of UMP
      residues to the 3'-ends of preexisting RNA. In most cases, however, the
      biological significance of these modifications remains elusive. As an exception,
      the RNA terminal uridylyl transferases (TUTases) of the mRNA editing complex
      within mitochondria of Trypanosomatidae have been characterized in great detail.
      Current knowledge on those editing enzymes has been summarized recently by R.
      Aphasizhev [Cell. Mol. Life Sci. 62 (2005) 2194-203] and, therefore, will not be
      included here. Rather, this review will focus on cellular non-editing TUTases,
      characterized by distinct modes of catalytic activity and substrate specificity.
      Putative biological functions of this rapidly growing number of RNA modifying
      enzymes are discussed.

PMID- 18067876
TI  - Intravitreal bevacizumab for treatment of neovascular age-related macular
      degeneration: a one-year prospective study.
AB  - PURPOSE: To investigate the efficacy of intravitreal bevacizumab for treatment of
      neovascular age-related macular degeneration (AMD). DESIGN: Prospective, open
      label, nonrandomized clinical study. METHODS: Sixty patients (60 eyes) with
      subfoveal choroidal neovascular membrane (CNV) attributable to AMD participated
      in this study at the American University of Beirut and Hotel Dieu de France
      Retina Clinics. All lesion types were included except for retinal angiomatous
      proliferation. In the initial treatment phase, intravitreal bevacizumab (2.5
      mg/0.1 ml) was given at baseline, and then two additional monthly injections were
      given if the macula was not dry on optical coherence tomography. The criteria for
      re-injection after the induction phase were presence of new fluid in the macula,
      increased central retinal thickness (CRT) at least 100 microm, loss of at least
      five letters of vision with increased fluid in the macula, new classic CNV or new
      macular hemorrhages. Main outcome measure was the proportion of eyes losing <15
      letters of vision after 12 months. RESULTS: Fifty-one patients (51 eyes)
      completed the 12 months. Mean visual acuity improved from 45.7 letters at
      baseline to 53.1 letters at 12 months (P = .004), and 47 eyes (92.2%) lost <15
      letters. Mean CRT decreased from 327.4 microm at baseline to 227.8 microm at 12
      months (P < .001). A mean of 3.4 injections were given over the course of the
      study, and no ocular or systemic side-effects were noted. CONCLUSION: Eyes with
      neovascular AMD treated with intravitreal bevacizumab over 12 months had
      significant anatomical and functional improvement. Further studies need to
      confirm the long-term efficacy of this treatment.

PMID- 18067877
TI  - New interneurons in the adult neocortex: small, sparse, but significant?
AB  - During the last decade, the intense study of adult hippocampal neurogenesis has
      led to several new lines of inquiry in the field of psychiatry. Although it is
      generally believed that adult mammalian neurogenesis is restricted to the
      hippocampus and olfactory bulb, a growing number of studies have described new
      neurons in the adult neocortex in both rodents and nonhuman primates.
      Interestingly, all of the new neurons observed in these studies have features of
      interneurons rather than pyramidal cells, the largest neuronal population of the
      neocortex. In this review, we discuss features of these interneurons that may
      explain why cortical neurogenesis has been so difficult to detect. In addition,
      these features suggest ways that production of even a small numbers of new
      neurons in the adult cortex could make a significant impact on neocortical
      function.

PMID- 18067880
TI  - Metal-heptaiodide interactions in cyclomaltoheptaose (beta-cyclodextrin)
      polyiodide complexes as detected via Raman spectroscopy.
AB  - The Raman spectra of the cyclomaltoheptaose (beta-cyclodextrin, beta-CD)
      polyiodide complexes (beta-CD)(2).NaI(7).12H(2)O, (beta-CD)(2).RbI(7).18H(2)O,
      (beta-CD)(2).SrI(7).17H(2)O, (beta-CD)(2).BiI(7).17H(2)O and (beta
      CD)(2).VI(7).14H(2)O (named beta-M, M stands for the corresponding metal) are
      investigated in the temperature range of 30-140 degrees C. At room temperature
      all systems show an initial strong band at 178 cm(-1) that reveals similar
      intramolecular distances of the disordered I(2) units (approximately 2.72 A).
      During the heating process beta-Na and beta-Rb display a gradual shift of this
      band to the final single frequency of 166 cm(-1). In the case of beta-Sr and beta
      Bi, the band at 178 cm(-1) is shifted to the final single frequencies of 170 and
      172 cm(-1), respectively. These band shifts imply a disorder-order transition of
      the I(2) units whose I-I distance becomes elongated via a symmetric charge
      transfer interaction I(2)<--I3(-)-->I(2). The different final frequencies
      correspond to different bond lengthening of the disordered I(2) units during
      their transformation into well-ordered ones. In the Raman spectra of beta-V, the
      initial band at 178 cm(-1) is not shifted to a single band but to a double one of
      frequencies 173 and 165 cm(-1), indicating a disorder-order transition of the
      I(2) molecules via a non-symmetric charge-transfer interaction I(2)<--I3(-)-
      >I(2). The above spectral data show that the ability of I3(-) to donate electron
      density to the attached I(2) units is determined by the relative position of the
      different metal ions and their ionic potential q/r. The combination of the
      present results with those obtained from our previous investigations reveals that
      cations with an ionic potential that is lower than approximately 1.50 (Cs(+),
      Rb(+), Na(+), K(+) and Ba(2+)) do not affect the Lewis base character of I3(-).
      However, when the ionic potential of the cation is greater than approximately
      1.50 (Li(+), Sr(2+), Cd(2+), Bi(3+) and V(3+)), the M(n+)...I3(-) interactions
      become significant. In the case of a face-on position of the metal (Sr(2+),
      Bi(3+)) relative to I3(-), the charge-transfer interaction is symmetric. On the
      contrary, when the metal (Li(+), Cd(2+), V(3+)) presents a side-on position
      relative to I3(-), the charge-transfer interaction is non-symmetric.

PMID- 18067879
TI  - Progesterone attenuates cocaine-induced conditioned place preference in female
      rats.
AB  - Progesterone replacement attenuates the intensity of cocaine-induced conditioned
      place preference (CPP) behaviors in female rats. The present study aimed to
      expand that finding by (i) determining the role of progesterone in the
      acquisition and/or expression of cocaine-induced CPP and (ii) determining if
      progesterone's effects might be meditated through learning and memory. To this
      end, female rats were administered progesterone during cocaine conditioning or
      object recognition tasks; rats received subcutaneous injections of progesterone
      (500 microg) or vehicle (sesame oil) 4 h before saline or cocaine (5 mg/kg) on
      conditioning days (acquisition phase) or before testing (expression phase or
      object recognition tasks). Progesterone treatment during both the acquisition and
      the expression phases of cocaine conditioning blocked cocaine-induced CPP.
      Progesterone affected neither the number of entrances and explorations in the CPP
      chambers nor the ambulatory and rearing behaviors. In the object recognition task
      (a non-spatial learning and memory task), progesterone treatment had no effect.
      However, in the object placement task (a spatial learning and memory task),
      progesterone treatment significantly impaired retention in hormone-treated rats
      as compared with control groups. These results suggest that progesterone
      treatment interferes with cocaine-induced reward associations, possibly through
      effects on spatial working memory consolidation The observed effects of acute
      progesterone treatment on cocaine-induced CPP may in part contribute reported
      menstrual effects and sex disparities in overall cocaine use and rates of
      relapse.

PMID- 18067881
TI  - Synthesis of 2-deoxy-D-arabino/lyxo-hexopyranosyl disaccharides.
AB  - Synthesis of 2-deoxy-D-arabino/lyxo-hexopyranosyl disaccharides is reported. In
      these, the disaccharides contain 2-deoxy-arabino-hexopyranosyl and 2-deoxy-lyxo
      hexopyranosyl sugars as either the reducing or the non-reducing or both the sugar
      units of the disaccharides. The activated 2-deoxy-1-thioglycosides served as the
      common precursors to prepare the 2-deoxy disaccharides with the above
      configurations.

PMID- 18067882
TI  - Photoprotective effects of glucomannan isolated from Candida utilis.
AB  - Glucomannans belong to yeast and fungal cell wall polysaccharides with known
      immunostimulatory and radioprotective effects. However, glucomannan protective
      effects against pathological consequences of skin exposure to short wavelength
      solar light, ultraviolet (UV) radiation, are unclear. Herein, a highly branched
      glucomannan (GM) isolated from the cell wall of Candida utilis, a member of the
      alpha-(1-->6)-D-mannan group, was tested for its photoprotective effects in an in
      vitro model of UVB-irradiated human keratinocytes and an in vivo model of UV
      induced erythema formation in human volunteers. GM suppressed the UVB-induced
      decrease of keratinocyte viability, which was connected with the suppression of
      UVB-induced keratinocyte apoptosis. GM reduced UVB-mediated caspase activation
      together with suppression of DNA fragment release into the cytoplasm.
      Furthermore, GM suppressed UVB-induced gene expression of pro-inflammatory
      markers including nuclear factor kappa B, inducible nitric oxide synthase,
      interleukins 8 and 1, together with suppression of prostaglandin E2 and
      interleukin 1alpha protein release. In vivo, GM decreased UV-induced skin
      erythema formation, which was correlated with a decrease of phosholipase A(2)
      activity within the stratum corneum. It could be concluded that GM isolated from
      C. utilis possesses significant photoprotective effects on human keratinocytes in
      vitro as well as in vivo.

PMID- 18067884
TI  - When is cataphoric reference recognised?
AB  - Pronouns typically have explicit antecedents in the prior discourse otherwise
      processing difficulty is experienced. However, it has been argued [Gordon, P. C.,
      & Hendrick, R. (1997). Intuitive knowledge of linguistic co-reference. Cognition,
      62, 325-370; Gordon, P. C., & Hendrick, R. (1998). The representation and
      processing of co-reference in discourse. Cognitive Science, 22, 389-424] that
      when a pronoun appears in a preposed subordinate clause (as in, Before she began
      to sing, Susan stood up), incremental interpretation is suspended and no
      antecedent is immediately sought, since the pronoun cannot be resolved until the
      main clause is encountered. We report results from an eye-tracking study showing
      that on encountering a pronoun that has no prior antecedent (compared to cases
      where there is an explicit prior antecedent), readers experience immediate
      difficulty whether or not the pronoun appears in a preposed subordinate clause,
      suggesting that attempted incremental interpretation is not suspended in these
      cases.

PMID- 18067883
TI  - Invariant chain modulates HLA class II protein recycling and peptide presentation
      in nonprofessional antigen presenting cells.
AB  - The expression of MHC class II molecules and the invariant chain (Ii) chaperone,
      is coordinately regulated in professional antigen presenting cells (APC). Ii
      facilitates class II subunit folding as well as transit and retention in mature
      endosomal compartments rich in antigenic peptides in these APC. Yet, in
      nonprofessional APC such as tumors, fibroblasts and endocrine tissues, the
      expression of class II subunits and Ii may be uncoupled. Studies of
      nonprofessional APC indicate class II molecules access antigenic peptides by
      distinct, but poorly defined pathways in the absence of Ii. Here, investigations
      demonstrate that nonprofessional APC such as human fibroblasts lacking Ii
      internalize antigenic peptides prior to the binding of these ligands to recycling
      class II molecules. By contrast, fibroblast lines expressing Ii favor exogenous
      peptides binding directly to cell surface class II molecules without a need for
      ligand internalization. Endocytosis of class II molecules was enhanced in cells
      lacking Ii compared with Ii-expressing APC. These results suggest enhanced
      reliance on the endocytic recycling pathway for functional class II presentation
      in nonprofessional APC.

PMID- 18067885
TI  - Spatial specificity of mesodermal even-skipped expression relies on multiple
      repressor sites.
AB  - Individual cardiac progenitors emerge at defined positions within each segment in
      the trunk mesoderm. Their specification depends on segmental information from the
      pre-patterned ectoderm, which provides positional information to the underlying
      cardiac mesoderm via inductive signals. This pattern is further reinforced by
      repressive interactions between transcription factors that are expressed in
      neighboring sets of cardiac progenitors. For example, even-skipped (eve) and
      ladybird early (lbe) gene products mark adjacent cardiac cell clusters within a
      segment, and their antagonistic interaction results in mutually exclusive
      expression domains. Lbe acts directly on the eve mesodermal enhancer (eme) to
      participate in restricting its expression anteriorly. We hypothesized that
      additional repressive activities must regulate the precise pattern of eve
      expression in the cardiac mesoderm via this enhancer. In this study, we
      identified two additional repressor motifs: 4 copies of an "AT"-rich motif (M1a
      d) and 2 copies of an "GC"-rich motif (M2 a,b), which when mutated cause
      expansion of eme-dependent reporter gene expression. We have also examined
      potential negative regulators of eve and found that their overexpression is
      sufficient to repress eve as well as the eme enhancer via these sites. Our data
      suggest that a combination of factors is likely to interact with multiple
      essential repressor sites to confer precise spatial specificity of eve expression
      in the cardiac mesoderm.

PMID- 18067887
TI  - Cdx2 acts downstream of cell polarization to cell-autonomously promote
      trophectoderm fate in the early mouse embryo.
AB  - The first lineage decision during mouse development is the establishment of
      trophectoderm and inner cell mass lineages, morphologically distinguishable at
      the blastocyst stage. The Caudal-like transcription factor Cdx2 is required for
      repression of inner cell mass genes Oct4 and Nanog in the trophectoderm.
      Expression of Cdx2 in the trophectoderm is thus one of the earliest known events
      in lineage determination. However, it is not clear whether the Cdx2 expression
      pattern is the cause or the consequence of this first lineage decision. Here, we
      show that Cdx2 is initially ubiquitously expressed, and becomes progressively
      upregulated in outside, future trophectoderm cells prior to blastocyst formation.
      Ubiquitous Cdx2 expression begins around the time of cell polarization, but we
      show that cell polarization is independent of zygotic Cdx2. Finally, we show
      functionally that Cdx2 is downstream of lineage allocation since Cdx2 mutant
      cells, which show cell-autonomous defects in expression of Oct4, Nanog, and the
      trophectoderm marker Eomesodermin, do not preferentially contribute to inner cell
      mass in chimeric blastocysts. Cdx2 therefore appears to act downstream of the
      first lineage decision, suggesting that processes influencing lineage allocation
      or morphogenesis may regulate Cdx2 expression along the inside/outside axis of
      the embryo.

PMID- 18067886
TI  - Characterization of the Drosophila segment determination morphome.
AB  - Here we characterize the expression of the full system of genes which control the
      segmentation morphogenetic field of Drosophila at the protein level in one
      dimension. The data used for this characterization are quantitative with cellular
      resolution in space and about 6 min in time. We present the full quantitative
      profiles of all 14 segmentation genes which act before the onset of gastrulation.
      The expression patterns of these genes are first characterized in terms of their
      average or typical behavior. At this level, the expression of all of the genes
      has been integrated into a single atlas of gene expression in which the
      expression levels of all genes in each cell are specified. We show that
      expression domains do not arise synchronously, but rather each domain has its own
      specific dynamics of formation. Moreover, we show that the expression domains
      shift position in the direction of the cephalic furrow, such that domains in the
      anlage of the segmented germ band shift anteriorly while those in the presumptive
      head shift posteriorly. The expression atlas of integrated data is very close to
      the expression profiles of individual embryos during the latter part of the
      blastoderm stage. At earlier times gap gene domains show considerable variation
      in amplitude, and significant positional variability. Nevertheless, an average
      early gap domain is close to that of a median individual. In contrast, we show
      that there is a diversity of developmental trajectories among pair-rule genes at
      a variety of levels, including the order of domain formation and positional
      accuracy. We further show that this variation is dynamically reduced, or
      canalized, over time. As the first quantitatively characterized morphogenetic
      field, this system and its behavior constitute an extraordinarily rich set of
      materials for the study of canalization and embryonic regulation at the molecular
      level.

PMID- 18067889
TI  - Lamellipodia nucleation by filopodia depends on integrin occupancy and downstream
      Rac1 signaling.
AB  - Time-lapse video-microscopy unambiguously shows that fibroblast filopodia are the
      scaffold of lamellipodia nucleation that allows anisotropic cell spreading. This
      process was dissected into elementary stages by monitoring cell adhesion on
      micropatterned extracellular matrix arrays of various pitches. Adhesion
      structures are stabilized by contact with the adhesive plots and subsequently
      converted into lamellipodia-like extensions starting at the filopodia tips. This
      mechanism progressively leads to full cell spreading. Stable expression of the
      dominant-negative Rac1 N17 impairs this change in membrane extension mode and
      stops cell spreading on matrix arrays. Similar expression of the dominant
      negative Cdc42 N17 impairs cell spreading on homogenous and structured substrate,
      suggesting that filopodia extension is a prerequisite for cell spreading in this
      model. The differential polarity of the nucleation of lamellipodial structures by
      filopodia on homogenous and structured surfaces starting from the cell body and
      of filopodia tip, respectively, suggested that this process is triggered by areas
      that are in contact with extracellular matrix proteins for longer times.
      Consistent with this view, wild-type cells cannot spread on microarrays made of
      function blocking or neutral anti-beta 1 integrin antibodies. However, stable
      expression of a constitutively active Rac1 mutant rescues the cell ability to
      spread on these integrin microarrays. Thereby, lamellipodia nucleation by
      filopodia requires integrin occupancy by matrix substrate and downstream Rac1
      signaling.

PMID- 18067890
TI  - Murine epidermal side population possesses unique angiogenic properties.
AB  - Total epidermal keratinocytes are a heterogeneous population of cells, including
      undifferentiated stem/progenitor cells (EpSPs) and their more differentiated
      progeny (Non-SP cells). Our previous in vivo data showed that EpSPs enhanced
      blood flow restoration when injected into an ischemic limb, whereas Non-SP cells
      had no significant effect on in vivo blood flow restoration. However, the
      cellular and molecular mechanisms of this observation remain largely unknown.
      Therefore, the aim of this study was to investigate the angiogenic properties of
      different epidermal subpopulations in vitro and the mechanism by which EpSPs
      enhanced blood flow in vivo. Using migration assay and capillary network
      formation, we show that EpSPs secrete higher levels of pro-angiogenic molecules
      compared to Non-SP cells, unsorted keratinocytes and fibroblasts in vitro.
      Secretion of vascular endothelial growth factor (VEGF) was detected at higher
      levels in EpSP conditioned medium than the medium conditioned by other epidermal
      subpopulations and fibroblasts. Also, RT-PCR analyses revealed a unique
      angiogenic gene profile for EpSPs. Finally, gene array data indicate significant
      changes in angiogenic gene expression six days after cell injection in murine
      ischemic limbs. Therefore, we conclude that EpSPs possess unique angiogenic
      properties and that these cells may be indirectly responsible for the angiogenic
      response previously observed in our ischemic limb model.

PMID- 18067888
TI  - Foreign body-type multinucleated giant cell formation requires protein kinase C
      beta, delta, and zeta.
AB  - Multinucleated giant cells are a classic cellular feature of chronic
      inflammation, although the mechanism of macrophage fusion leading to their
      formation is not well understood. Here, we investigate the participation of
      protein kinase C (PKC) in the interleukin (IL)-4-induced fusion of human monocyte
      derived macrophages and foreign body giant cell (FBGC) formation in vitro. The
      PKC inhibitors H-7 and calphostin C attenuated macrophage fusion, whereas H-8,
      which is more selective for PKA and PKG, did not. Macrophage fusion was also
      prevented by the phospholipase C inhibitor, Et-18-OCH(3), the PKC isoform
      inhibitors GO6983 or rottlerin and by peptide inhibitors for PKC (20-28),
      PKCbeta, or PKCzeta but not by HBDDE or peptide inhibitors for PKCvarepsilon or
      PKA. In cultures of fusing macrophages/FBGC, we detected only PKCalpha, beta,
      delta, and zeta by immunoprecipitation and immunoblotting, and we also observed
      strong expression of these isoforms by immunocytochemistry. Our collective
      results suggest that the gamma, epsilon, eta, mu, theta, or iota PKC isoforms are
      not required in the mechanism of IL-4-induced macrophage fusion; whether PKCalpha
      is required is unclear. However, new evidence is provided that FBGC formation is
      supported by PKCbeta, PKCdelta, and PKCzeta in combined diacylglycerol-dependent
      (PKCbeta and PKCdelta) and -independent (PKCzeta) signaling pathways.

PMID- 18067891
TI  - Telomerase inhibition in a mouse cell line with long telomeres leads to rapid
      telomerase reactivation.
AB  - The indefinite growth of cancer cells requires telomere maintenance, which, in
      the majority of mammalian cancers is mediated via the enzyme telomerase. The core
      components of telomerase are a catalytic reverse transcriptase (hTERT in human,
      mTERT in mouse) and an RNA (TR) that contains the template for the replenishment
      of telomeres. Fundamental differences in human and mouse telomerase and telomere
      biology should be considered when using mouse models for the study of human
      cancers. The responses to telomerase inhibition by the expression of a
      catalytically-inactive dominant-negative mutant of hTERT (hTERT-DN) vary in human
      cells with different telomere lengths. Only one similar study has been performed
      in a mouse cell line with short telomeres (RenCa, 7 kb). Thus, we asked whether
      the responses to telomerase inhibition are also telomere-length dependent in
      mouse cells by analyzing long-term stable expression of mTERT-DN in the CB17 cell
      line (telomere length, 11 kb). A brief initial telomerase inhibition was
      insufficient to mediate telomere shortening and led to extremely rapid telomerase
      reactivation due to an increase in the level of expression of the endogenous
      mTERT. Thus, mouse cells, in contrast to human cells may not tolerate telomerase
      inhibition by introduction of mTERT-DN, independently of telomere length.

PMID- 18067892
TI  - Phylogenetic analysis of Cystoisospora species at the rRNA ITS1 locus and
      development of a PCR-RFLP assay.
AB  - The ITS1 sequences for C. suis, C. belli, C. rivolta, C. felis, and C. ohioensis
      like oocysts were determined and a diagnostic PCR-RFLP assay specific for
      Cystosisopora species was developed. Phylogenetic analysis of ITS1 sequences of
      Cystosisopora species along with ITS1 sequences for Toxoplasma, Neospora,
      Sarcocystis and Eimeria spp. using distance, minimum evolution and parsimony
      based methods confirmed previous studies, which suggested that the genus
      Cystoisospora does not belong to the family Eimeriidae, but should be classified
      together with the cyst-forming coccidia in the family Sarcocystidae.

PMID- 18067893
TI  - Oestrogen receptor alpha and beta in female rat pituitary cells: an
      immunochemical study.
AB  - Estradiol is a critical factor in the anterior pituitary secretory activity of
      mammalian females. Previous reports have demonstrated the presence of oestrogen
      receptor alpha (ERalpha) and beta (ERbeta) in specific anterior pituitary cells
      from ovariectomized rats, as well as in the whole anterior pituitary at
      particular stages of the rat oestrous cycle. However, the ERalpha and ERbeta
      distribution patterns in specific hormone producing cells of the anterior
      pituitary during the oestrous cycle remain to be clarified. The purpose of this
      study was to determine the cellular and subcellular distribution of both ER
      subtypes during the rat oestrous cycle, using immunochemistry at light- and
      electron-microscope levels. ERalpha-immunoreactive (ir) cells mainly corresponded
      to PRL-ir cells and, to a lesser extent, to TSH-, FSH- and GH-ir cells. ERbeta-ir
      cells corresponded to a few GH-, PRL- and FSH-ir cells, whichever the phase of
      the cycle. ERalpha-ir was found either in the cytoplasm and/or the nucleus,
      depending on the phase of the oestrous cycle, while ERbeta-ir was always detected
      in the cytoplasm. Both ER-subtypes were immunoreactives inside the rough
      endoplasmic reticulum (RER), secretory vesicles (SV) and free in the cytosol. The
      highest number of ERalpha-ir cells was consistently found at pro-oestrus midday
      and the lowest at metaoestrous, while the number of ERbeta-ir cells was low in
      all stages of the cycle. These results indicate that the genomic actions of
      oestrogen in the anterior pituitary cells during the oestrous cycle are mediated
      by ERalpha. However, the localization of ERalpha and ERbeta in the RER and SV
      suggest a different translational and/or post-translational pathway, which could
      be involved in non-genomic mechanisms.

PMID- 18067895
TI  - 15-Lipoxygenase-2 expression in human macrophages induces chemokine secretion and
      T cell migration.
AB  - BACKGROUND: We determined previously that hypoxia results in increased 15
      lipoxygenase type 2 (15-LOX-2) expression and CXCL8 secretion in macrophages.
      This study sought to determine whether 15-LOX-2 expression links directly with
      the secretion of inflammatory molecules in macrophages and also investigated its
      subsequent effects on T cell migration. METHODS: Adenovirus-mediated gene
      delivery caused overexpression of 15-LOX-2 in human macrophages. We used
      cytometric bead array to measure chemokine secretion, and assessed T cell
      migration by counting cells in chemotaxis chambers. Expression of chemokine
      receptors was determined by FACS analysis. Using siRNA, we reduced 15-LOX-2
      expression in human macrophages. We used scrambled siRNA as control. RESULTS:
      Macrophages that overexpress 15-LOX-2 showed increased secretion of chemokine
      CXCL10 after 24h incubation. In addition, preconditioned medium from 15-LOX-2
      overexpressing cells increased T cell migration and surface expression of CXCR3,
      the CXCL10 receptor. Knockdown of 15-LOX-2 expression decreased CXCL10 secretion
      from hypoxic macrophages and also reduced T cell migration. CONCLUSION: In
      macrophages, overexpression of 15-LOX-2 results in increased secretion of CXCL10
      and CCL2. Products released in response to increased 15-LOX-2 activation lead to
      increased expression of CD69, the T cell activation marker as well as increased T
      cell migration. Therefore, increased expression of 15-LOX-2 induced by hypoxia
      may participate in T cell recruitment in diseases such as atherosclerosis.

PMID- 18067894
TI  - An alternate pathway for androgen regulation of brain function: activation of
      estrogen receptor beta by the metabolite of dihydrotestosterone, 5alpha
      androstane-3beta,17beta-diol.
AB  - The complexity of gonadal steroid hormone actions is reflected in their broad and
      diverse effects on a host of integrated systems including reproductive
      physiology, sexual behavior, stress responses, immune function, cognition, and
      neural protection. Understanding the specific contributions of androgens and
      estrogens in neurons that mediate these important biological processes is central
      to the study of neuroendocrinology. Of particular interest in recent years has
      been the biological role of androgen metabolites. The goal of this review is to
      highlight recent data delineating the specific brain targets for the
      dihydrotestosterone metabolite, 5alpha-androstane, 3beta,17beta-diol (3beta
      Diol). Studies using both in vitro and in vivo approaches provide compelling
      evidence that 3beta-Diol is an important modulator of the stress response
      mediated by the hypothalmo-pituitary-adrenal axis. Furthermore, the actions of
      3beta-Diol are mediated by estrogen receptors, and not androgen receptors, often
      through a canonical estrogen response element in the promoter of a given target
      gene. These novel findings compel us to re-evaluate the interpretation of past
      studies and the design of future experiments aimed at elucidating the specific
      effects of androgen receptor signaling pathways.

PMID- 18067898
TI  - Joint moment work during the stance-to-swing transition in hemiparetic subjects.
AB  - Following stroke many individuals are left with neurological and functional
      deficits, including hemiparesis, which impair their ability to walk. Our previous
      work reported that propulsion of the paretic leg during pre-swing is impaired and
      may limit gait speed and knee flexion during swing. To elucidate the mechanism of
      this impairment, we assessed the mechanical work produced by the hip, knee, and
      ankle moments during pre-swing of the paretic limb in a group of stroke subjects
      and compared it with the work produced by non-disabled controls walking at
      similar speeds. Kinematic and kinetic gait data were collected from 23
      hemiparetic and 10 control subjects. The hemiparetic subjects walked at their
      self-selected speeds. The controls walked at their self-selected and two or three
      slower speeds. Even when compared to controls walking at slow speeds, ankle
      plantarflexor work during pre-swing was greatly reduced (-0.136+/-0.062J/kg) in
      the hemiparetic subjects. Differences in hip (+0.006+/-0.020J/kg) and knee
      (+0.040+/-0.026J/kg) moment work partially offset the reduction in ankle work,
      but net joint moment work was still significantly reduced (-0.088+/-0.056J/kg).
      The reduction in work accounts for the low energy of the paretic limb at the
      stance-to-swing transition previously reported. Future investigation is needed to
      determine if targeted training of the plantarflexors in the paretic limb improves
      swing-phase function and locomotor performance in hemiparetic individuals.

PMID- 18067897
TI  - Innate immunity has a dual effect on vascular healing: suppression and
      aggravation of neointimal formation and remodeling post-endotoxin challenge.
AB  - BACKGROUND: Inflammation is important to vascular repair following injury,
      modulating neointimal proliferation and remodeling. Previously, we have shown
      that a low-intensity inflammatory response aggravates neointimal formation
      following balloon and stent injury. The present study examined whether modulation
      of the extent and timing of nonspecific inflammation mediates the local vascular
      response in an additive unidirectional or rather a bidirectional fashion. METHODS
      AND RESULTS: Rabbits subjected to denudation and balloon injury of the iliac
      artery were treated with low (1 microg/kg) or high (100 microg/kg) doses of
      bacterial endotoxin (LPS) immediately after injury, or with early high-dose LPS
      administered 3 days prior to injury (preconditioning). Neointimal formation at 28
      days was significantly increased in the low-dose group (0.537+/-0.059 mm(2)) as
      compared with controls (0.3+/-0.03 mm(2)). High-dose LPS did not significantly
      affect neointimal formation while early high dose significantly reduced neointima
      (0.296+/-0.033 and 0.194+/-0.025 mm(2), respectively, n=12-14/group). Arterial
      wall and systemically circulating interleukin-1 beta levels, and monocyte CD14
      activation correlated with neointimal formation. Vascular remodeling was
      accelerated in animals treated with low- or high-dose LPS while not affected in
      the preconditioned group. Remodeling index inversely correlated with arterial
      matrix metalloproteinase-2 levels 6 days after injury. CONCLUSIONS: The extent
      and timing of nonspecific inflammation that is concurrent with vascular injury
      can determine different and opposite vascular repair patterns.

PMID- 18067899
TI  - Cluster and principal component analysis for Kovats' retention indices on apolar
      and polar stationary phases in gas chromatography.
AB  - An extended set of Kovats' retention indices of 137 organic compounds obtained at
      405.15K with C 78 standard alkane and with standalone polar interactive groups
      was analyzed. The retention data determined using gas chromatography were
      subjected to hierarchical cluster analysis and principal component analysis to
      detect structure in the data and to classify retention indices and solutes alike.
      The statistical evaluation of the retention data explored the correlation between
      the retention indices of the solutes and the similarities/differences of the
      stationary liquids. A set of chromatographic systems was selected as possible new
      standards relating to linear solvation energy relationships based on the
      chemometric data reduction. The new molecular descriptors based on retention
      indices were tested in correlation models for normal boiling point and olive
      oil/gas partition coefficient data using ridge regression. The ridge regression
      provided new ways for variable selection. The normal boiling points of organic
      compounds can reasonably be described using retention indices on apolar (C78) and
      polar (trifluoro, hydroxy, bromo and cyano) model compounds. The partition
      coefficients between olive oil and the gas phase can similarly be well correlated
      with retention indices on apolar (C78) and polar (tetramethoxy, trifluoro and
      hydroxy) model compounds.

PMID- 18067900
TI  - Ion mobility spectrometry detection for gas chromatography.
AB  - The hyphenated analytical method in which ion mobility spectrometry (IMS) is
      coupled to gas chromatography (GC) provides a versatile alternative for the
      sensitive and selective detection of compounds after chromatographic separation.
      Providing compound selectivity by measuring unique gas phase mobilities of
      characteristic analyte ions, the separation and detection process of gas
      chromatography-ion mobility spectrometry (GC-IMS) can be divided into five
      individual steps: sample introduction, compound separation, ion generation, ion
      separation and ion detection. The significant advantage of a GC-IMS detection is
      that the resulting interface can be tuned to monitor drift times/ion mobilities
      (as a mass spectrometer (MS) can be tuned to monitor ion masses) of interest,
      thereby tailoring response characteristics to fit the need of a given separation
      problem. Because IMS separates ions based on mobilities rather than mass,
      selective detection among compounds of the same mass but different structures are
      possible. The most successful application of GC-IMS to date has been in the
      international space station. With the introduction of two-dimensional gas
      chromatography (2D-GC), and a second type of mobility detector, namely
      differential mobility spectrometry (DMS), GC prior to mobility measurements can
      now produce four-dimensional analytical information. Complex mixtures in
      difficult matrices can now be analyzed. This review article is intended to
      provide an overview of the GC-IMS/DMS technique, recent developments, significant
      applications, and future directions of the technique.

PMID- 18067902
TI  - Design and synthesis of a novel fluorescent reagent, 6-oxy-(ethylpiperazine)-9
      (2'-methoxycarbonyl) fluorescein, for carboxylic acids and its application in
      food samples using high-performance liquid chromatography.
AB  - A novel derivatization reagent for carboxylic acids, 6-oxy-(ethylpiperazine)-9
      (2'-methoxycarbonyl)fluorescein (EPMF) has been well designed and synthesized. It
      was used to label 13 fatty acids, n-butyric acid (C4), n-valeric acid (C5), n
      hexanoic acid (C6), n-heptanoic acid (C7), n-octanoic acid (C8), n-nonanoic acid
      (C9), n-decanoic acid (C10), lauric acid (C12), myristic acid (C14), palmitic
      acid (C16), stearic acid (C18), oleic acid (C18:1) and linoleic acid (C18:2),
      successfully. The derivatization reaction with fatty acids was completed at 50
      degrees C, 50 min. The derivatives of fatty acids were separated on a C18
      reversed-phase column with gradient elution and fluorescence detection at
      lambda(ex)/lambda(em)=469/518 nm. The detection limits obtained were 0.4-2 nmol
      L(-1) (signal-to-noise ratio of 3). The proposed method has been applied to the
      quantification of fatty acids in edible oil with recoveries over 93%. It has been
      demonstrated that EPMF is a prominent derivatization reagent for fatty acids and
      is suitable for HPLC.

PMID- 18067901
TI  - Study of some UV filters stability in chlorinated water and identification of
      halogenated by-products by gas chromatography-mass spectrometry.
AB  - This work studies the stability of three UV filters: 2-ethylhexyl salicylate
      (ES), 2-ethylhexyl 4-(dimethylamino) benzoate (EHPABA) and 2-hydroxy-4
      methoxybenzophenone (BP-3), in water samples containing low concentrations of
      free chlorine. Moreover, 2,4-dihydroxybenzophenone (2,4-DHBP), a metabolite of BP
      3, was also included in some of the performed assays. Experiments were carried
      out considering free chlorine and analytes concentrations at the microg mL(-1)
      and ng mL(-1) level, respectively. Gas chromatography with mass spectrometry was
      used to follow the time course of target compounds and to identify their
      halogenated by-products. Concentration of water samples with solid-phase
      extraction cartridges and derivatization (silylation) of some species were also
      employed to improve their detectability. Under the experimental conditions
      explored in this work, ES showed an acceptable stability whereas the rest of
      species reacted with free chlorine at significant rates following pseudo-first
      order kinetics. Their half-lives ranged from 0.4 to 25 min depending on the UV
      filter, chlorine concentration, water pH and presence of bromide traces. For
      EHPABA a relatively simple degradation pathway was established. It consisted of
      aromatic substitution of one atom of hydrogen per chlorine or bromide. The same
      reaction pattern was observed for BP-3 leading, in this case, to mono- and di
      halogenated by-products. In addition, several halogenated forms of 3
      methoxyphenol were identified as BP-3 cleavage by-products.

PMID- 18067903
TI  - Optimization of separation in two-dimensional high-performance liquid
      chromatography by adjusting phase system selectivity and using programmed elution
      techniques.
AB  - The overall peak capacity in comprehensive two-dimensional liquid chromatographic
      (LC x LC) separation can be considerably increased using efficient columns and
      carefully optimized mobile phases providing large differences in the retention
      mechanisms and separation selectivity between the first and the second dimension.
      Gradient-elution operation and fraction-transfer modulation by matching the
      retention and the elution strength of the mobile phases in the two dimensions are
      useful means to suppress the band broadening in the second dimension and to
      increase the number of sample compounds separated in LC x LC. Matching parallel
      gradients in the first and second dimension eliminate the necessity of second
      dimension column re-equilibration after the independent gradient runs for each
      fraction, increase the use of the available second-dimension separation time and
      can significantly improve the regularity of the coverage of the available
      retention space in LC x LC separations, especially with the first- and second
      dimension systems showing partial selectivity correlations. Systematic
      development of an LC x LC method with parallel two-dimensional gradients was
      applied for separation of phenolic acids and flavone compounds. Several types of
      bonded C18, amide, phenyl, pentafluorophenyl and poly(ethylene glycol) columns
      were compared using the linear free energy relationship method to find suitable
      column combination with low correlation of retention of representative standards.
      The phase systems were optimized step-by-step to find the mobile phases and
      gradients providing best separation selectivity for phenolic compounds. The
      optimization of simultaneous parallel gradients in the first and second dimension
      resulted in significant improvement in the utilization of the available two
      dimensional retention space.

PMID- 18067904
TI  - Solving matrix effects exploiting the second-order advantage in the resolution
      and determination of eight tetracycline antibiotics in effluent wastewater by
      modelling liquid chromatography data with multivariate curve resolution
      alternating least squares and unfolded-partial least squares followed by residual
      bilinearization algorithms II. Prediction and figures of merit.
AB  - A new powerful algorithm (unfolded-partial least squares followed by residual
      bilinearization (U-PLS/RBL)) was applied for first time on second-order liquid
      chromatography with diode array detection (LC-DAD) data and compared with a well
      known established method (multivariate curve resolution-alternating least squares
      (MCR-ALS)) for the simultaneous determination of eight tetracyclines
      (tetracycline, oxytetracycline, meclocycline, minocycline, metacycline,
      chlortetracycline, demeclocycline and doxycycline) in wastewaters. Tetracyclines
      were pre-concentrated using Oasis Max C18 cartridges and then separated on a
      Thermo Aquasil C18 (150 mm x 4.6mm, 5 microm) column. The whole method was
      validated using Milli-Q water samples and both univariate and multivariate
      analytical figures of merit were obtained. Additionally, two data pre-treatment
      were applied (baseline correction and piecewise direct standardization), which
      allowed to correct the effect of breakthrough and to reduce the total
      interferences retained after pre-concentration of wastewaters. The results showed
      that the eight tetracycline antibiotics can be successfully determined in
      wastewaters, the drawbacks due to matrix interferences being adequately handled
      and overcome by using U-PSL/RBL.

PMID- 18067905
TI  - Determination of relative response factors of impurities in paclitaxel with high
      performance liquid chromatography equipped with ultraviolet and charged aerosol
      detectors.
AB  - A case study was conducted to determine the relative response factors (RRFs) of
      paclitaxel-related impurities by high performance liquid chromatography (HPLC)
      equipped with an ultraviolet (UV) detector and charged aerosol detector (CAD) in
      tandem. The peak response using CAD was independent of analyte structure in an
      isocratic analysis for this application. After a sample containing known and
      unknown impurities was analyzed with HPLC-UV-CAD, an empirical approach was
      developed to calculate the RRFs for all impurities. The RRFs of known impurities
      were also determined by linear calibration curves. For known impurities, the RRFs
      values determined with two approaches are comparable. The new approach is
      effective yet simpler to determine the RRFs for unknown impurities or degradation
      products since the need for obtaining authentic pure materials was eliminated.

PMID- 18067906
TI  - Rapid synthesis of highly ordered Si-MCM-41.
AB  - A very short-time synthesis of highly ordered MCM-41 molecular sieve was
      formulated by using cetyltrimethylammonium bromide (CTAB) as the template and
      silica gel from SiliCycle as the silica source. The physical properties of MCM-41
      samples were characterized by X-ray diffraction (XRD), nitrogen physisorption,
      and transmission electron microscopy (TEM). The MCM-41 sample prepared in this
      study exhibited well defined long-range order and good hydrothermal stability. It
      was demonstrated that reducing the time of self-assembly step to 2 h during the
      synthesis had no unfavorable effect on the quality of MCM-41 materials.

PMID- 18067907
TI  - Advantages and limitations of the synchrotron based transmission X-ray microscopy
      in the study of the clay aggregate structure in aqueous suspensions.
AB  - This paper reports new application of new transmission X-ray microscopy powered
      by a synchrotron source for the study of aqueous based clay suspensions. This
      paper delineates the advantages and limitations of this method. The tested
      transmission X-ray microscopy (TXM) technique has shown good agreement with the
      cryo-stage SEM technique. The spacial resolution of this TXM technique is 60 nm
      and clay particles with diameter below 500 nm are clearly visible and their
      pseudohexagonal symmetry is recognizable in detail. It is clearly demonstrated
      the methodology of implementing TXM to study aqueous based clay suspensions that
      are close to approximately 60 nm tomographic resolution. The technique enables us
      to study discrete structure of clay suspensions in water and within aggregates.
      This has never been previously possible. Larger crystals, more compact aggregates
      and less colloidal fraction present in kaolinite from Georgia has impact on
      faster settling and gelling in denser suspension than for Birdwood kaolinite in
      which colloidal particles create gel-like networking in less dense aqueous
      suspension.

PMID- 18067908
TI  - Layered double hydroxide intercalated with p-methylbenzoate and p-bromobenzoate:
      molecular simulations and XRD analysis.
AB  - Samples of Mg4Al2 layered double hydroxide (LDH) intercalated with p
      methylbenzoate and p-bromobenzoate anions were prepared by reconstruction of
      calcined LDH. The interlayer arrangement of guests was investigated by molecular
      modeling combined with X-ray powder diffraction and thermogravimetry. Molecular
      modeling was carried out in a Cerius2 modeling environment. In both structures
      the guest anions adopt a nearly perpendicular arrangement of their long axis with
      respect to the host layers and they are anchored to the OH groups of the layers
      through COO* groups via electrostatic interactions. Molecular modeling revealed
      that both structures of the intercalates exhibit a certain disorder of guest
      anions in the interlayer space. In the case of LDH-p-methylbenzoate intercalate
      the anions tend to be situated in disordered rows, and the LDH-p-bromobenzoate
      intercalate exhibits a total disorientation of guest anions. A good agreement
      between calculated and measured X-ray diffraction patterns and between
      experimental and calculated basal spacings was obtained. In the LDH-p
      methylbenzoate intercalate d exp=16.96 A and d calc=16.97 A, and in the case of
      LDH-p-bromobenzoate intercalate d exp=17.19 A and d calc=17.40 A.

PMID- 18067909
TI  - Molecular dynamics simulations of structural features and diffusion properties of
      fullerene-in-water suspensions.
AB  - This study performs molecular dynamics (MD) simulations to investigate the
      structural features and diffusion properties of fullerene-in-water suspensions.
      The numerical results reveal that an organized structure of liquid water is
      formed close to the surface of the fullerene molecule, thereby changing the
      solid/liquid interfacial structure. The organized structure formation becomes
      more pronounced as the fullerene size is reduced. This observation implies that a
      transition zone exists between the organized liquid water layers and the random
      distribution region. Furthermore, the results indicate that the structural
      stability of fullerene-in-water suspensions improves as the fullerene volume
      fraction increases, but is insensitive to changes in the fullerene size. Finally,
      the simulation results reveal that the diffusion coefficient of the water
      molecules varies as a linear function of the fullerene loading, but is
      independent of the fullerene size.

PMID- 18067910
TI  - Colloidal aspects relating to direct incorporation of TiO2 nanoparticles into
      mesoporous spheres by an aerosol-assisted process.
AB  - Titania nanoparticles have been incorporated into spherical mesoporous silica
      powders by an aerosol-assisted synthesis process from both aqueous and ethanol
      based precursor dispersions. Transmission electron microscopy (TEM) showed that
      the titania nanoparticles exist as single particles or small aggregates within
      the mesoporous carrier particles and analysis of the nitrogen adsorption
      isotherms proved that the pore blocking of the particles is small. Particle size
      and zeta potential measurements showed that the addition of tetraethoxysiloxane
      (TEOS), and also hexadecyl trimethyl ammonium bromide (C16TAB) induced
      flocculation of the TiO2 nanoparticles. The higher yield and narrower size
      distribution of the composite powder produced from ethanol-based dispersions
      compared to the aqueous dispersions could be related to a smaller degree of
      aggregation, indicated by rheological measurements.

PMID- 18067911
TI  - Coprecipitation of gold(III) complex ions with manganese(II) hydroxide and their
      stoichiometric reduction to atomic gold (Au(0)): analysis by Mossbauer
      spectroscopy and XPS.
AB  - To elucidate the formation process of precursor of gold-supported manganese
      dioxide (MnO2), the coprecipitation behavior of [AuCl4-n(OH)n](-) (n=0-4)
      (Au(III)) complex ions with manganese(II) hydroxide (Mn(OH)2 and the change in
      their chemical state were examined. The Au(III) complex ions were rapidly and
      effectively coprecipitated with Mn(OH)(2) at pH 9. According to the Mossbauer
      spectra for gold (Au) coprecipitated with Mn(OH)2, below an Au content of 60 wt%
      in the coprecipitates, all of the coprecipitated Au existed in the atomic state
      (Au(0)), while, above an Au content of 65 wt%, part of the gold existed in the
      Au(III) state, and the proportion increased with increasing coprecipitated Au
      content. Based on the results of X-ray photoelectron spectroscopy, Mn(II) in
      Mn(OH)2 converted to Mn(IV) in conjunction with coprecipitation of Au(III)
      complex ions. These results indicate that the rapid stoichiometric reduction of
      Au(III) to Au(0) is caused by electron transfer from Mn(II) in Mn(OH)2 to the
      Au(III) complex ion through an Mn-O-Au bond.

PMID- 18067912
TI  - Adsorption of ions onto amorphous silica: ion exchange model.
AB  - Single site ion exchange model was applied for description of the published data
      on adsorption of sodium, calcium, cadmium, and zinc onto amorphous silica. The
      following equilibria were detected (25 degrees C; X-adsorption site; TotX=6
      micromol/m2): 2X + Na+ OH* <=> XNa+ XOH*, log K degree = 5.1, 3X + Me2+ +2OH*<=>
      XMe2+ 2XOH*, log K degree = 11.6 (Ca), 11.7 (Cd), 2X + Me2+ + 2OH* <=> XMeOH+ +
      XOH*, log K degree = 14.1 (Cd), 15.5 (Zn).

PMID- 18067913
TI  - Immobilization of iron tetrasulfophthalocyanine on functionalized MCM-48 and MCM
      41 mesoporous silicas: catalysts for oxidation of styrene.
AB  - Iron tetrasulfophthalocyanine (FePcS) has been anchored on the surface of
      functionalized MCM-48 and MCM-41 silicas by means of chemical bonding to
      aminosilane groups. The prepared materials, FePcS/NH2-MCM-48 and FePcS/NH2-MCM
      41, were characterized by diffuse reflectance UV-vis and infrared (IR)
      spectroscopies, low-angle X-ray diffraction (XRD), and surface area analysis
      (BET). The tendencies of FePcS absorption on functionalized MCM-48 and MCM-41
      were measured by UV-vis spectroscopy. The functionalized MCM-48 showed a larger
      amine to silica ratio than the functionalized MCM-41. Low-angle X-ray diffraction
      analysis showed that, by anchoring iron tetrasulfophthalocyanine into
      functionalized MCM-48 and MCM-41, the intensity of main reflection decreased. The
      catalytic activities of the supported iron tetrasulfophthalocyanine were examined
      by the oxidation of styrene in the presence of tert-butyl hydroperoxide. The
      FePcS/NH2-MCM-48 showed higher activity and durability in the liquid-phase
      oxidation of styrene under mild condition compared with the FePcS/NH2-MCM-41 and
      unsupported catalyst.

PMID- 18067914
TI  - Polyelectrolyte-surfactant complexes with long range order.
AB  - Mixtures of carboxymethyl cellulose (CMC) or hydrophobically modified CMC with an
      oppositely charged surfactant (benzyldimethyltetradecylammonium chloride) in
      water were prepared. When the global polymer concentration is 0.18% by weight and
      the surfactant content is high enough, a precipitate with hexagonal order is
      formed. The precipitate composition shows practically constancy in its water
      content and a slight diminution in polymer concentration when the global
      surfactant content is varied between 0.9 and 23 wt%. The lattice parameter in
      this phase decreases when the polymer/surfactant ratio in the phase increases;
      this variation is faster with CMC than with the hydrophobically modified CMC. In
      this way electrostatic and hydrophobic interactions are far from being additive.
      From the extrapolation to infinite dilution, the global interaction seems to
      depend on the substitution degree in the polymer. Additionally, the comparison
      between the radius at the polar-apolar interface in the cylinders and the lattice
      parameter as a function of polymer/surfactant ratio in the hexagonal phase is
      compatible with some of the alkyl chains belonging to the hydrophobically
      modified CMC being present in the aqueous zone.

PMID- 18067915
TI  - Effects of sampling context on the finite verb production of children with and
      without delayed language development.
AB  - Informal language sampling is ubiquitous in the study of developing grammatical
      abilities in children with and without delayed language, including study of
      grammatical abilities in the area of finite verb production. Finite verbs are
      particularly important to assess as they appear to be the grammatical morphemes
      most vulnerable to error in the language usage of children with specific language
      impairment (SLI). Although it is known that context and procedure of informal
      language sampling interact with language usage, this interaction has not been
      studied with regard to finite verb production for children with or without
      language delay. Therefore, this study examined the production of obligatory
      contexts for finite verbs, and the correct use of finite verb forms in these
      obligatory contexts, across four different language sampling contexts and
      procedures. Results revealed that finite verb production was sensitive to both
      group and context differences for preschool-age children with, and without,
      language impairment. LEARNING OUTCOMES: As a result of this activity, the reader
      should be able to: (1) describe the importance of assessing finite verb
      production in young children, (2) conceptualize processing demands as they relate
      to highly-structured versus less-structured, informal language sampling tasks,
      and (3) identify critical issues related to informal language sampling context
      effects on the finite verb production of young children.

PMID- 18067916
TI  - Identification of group 1 coronavirus antigen in multisystemic granulomatous
      lesions in ferrets (Mustela putorius furo).
AB  - Tissues from nine ferrets with granulomatous lesions similar to those seen in
      feline infectious peritonitis were examined histopathologically and
      immunohistochemically. Four main types of lesions were observed: diffuse
      granulomatous inflammation on serosal surfaces; granulomas with areas of
      necrosis; granulomas without necrosis; and granulomas with neutrophils. Other
      less commonly seen lesions were granulomatous necrotizing vasculitis and
      endogenous lipid pneumonia. FCV3-70 monoclonal antibody produced immunolabelling
      of group 1 coronavirus antigen in tissue samples from eight animals, the antigen
      being present in the cytoplasm of macrophages in the different types of
      granulomatous lesions.

PMID- 18067917
TI  - Age-related changes in children's understanding of effort and ability:
      implications for attribution theory and motivation.
AB  - Building on Nicholls's earlier work, we examined developmental changes in
      children's understanding of effort and ability when faced with a negative
      outcome. In a sample of 166 children and adolescents (ages 5-15 years), younger
      children conflated the meaning of effort and ability, explaining that smart
      students work hard, whereas older children understood effort and ability to be
      reciprocally related constructs, explaining that smart students do not need to
      work as hard. Understanding the reciprocal relation between effort and ability
      was correlated with age. Age-related changes in the meaning and correlates of
      effort and ability were also examined. Developmental implications for attribution
      theory and achievement motivation are discussed.

PMID- 18067918
TI  - Starvation suppresses cell proliferation that rebounds after refeeding in the
      midgut of the American cockroach, Periplaneta americana.
AB  - Starvation affects behavior, development, metabolism, reproduction, and longevity
      in almost all animals including insects. In the American cockroach, Periplaneta
      americana, we investigated the effect of starvation on organ size and cell
      proliferation activity of the midgut, over a period of one month, using anti
      bromodeoxyuridine (BrdU), and anti-phospho-histone H3 antibodies. Under
      starvation conditions, the midgut became clear and fragile while its length and
      diameter were reduced. Both the rate of BrdU-uptake in the nucleus and the
      mitotic activity shown by anti-phospho-histone H3 antibody decreased under long
      starvation up to half that of the continuously fed control. Refeeding restored
      BrdU-uptake and mitosis that overshot the fed control. When casein, starch, or
      cooking oil was fed as representative nutrient sources to the starved
      cockroaches, all restored BrdU-uptake, but non-nutrient, talc, did not. This
      study supports the hypothesis that P. americana has a homeostatic mechanism to
      regulate the cell population of the midgut epithelium according to changes in the
      nutritional environment.

PMID- 18067920
TI  - Interaction with 7SL RNA but not with HIV-1 genomic RNA or P bodies is required
      for APOBEC3F virion packaging.
AB  - Human cytidine deaminase apolipoprotein B mRNA-editing catalytic polypeptide-like
      3F (APOBEC3F, or A3F), like APOBEC3G, has broad antiviral activity against
      diverse retroelements, including Vif-deficient human immunodeficiency virus (HIV)
      1. Its antiviral functions are known to rely on its virion encapsidation and be
      suppressed by HIV-1 Vif, which recruits Cullin5-based E3 ubiquitin ligases.
      However, the factors that mediate A3F virion packaging have not yet been
      identified. In this study, we demonstrate that A3F specifically interacts with
      cellular signal recognition particle (SRP) RNA (7SL RNA), which is selectively
      packaged into HIV-1 virions. Efficient packaging of 7SL RNA as well as A3F was
      mediated by the RNA-binding nucleocapsid domain of HIV-1 Gag. Reducing 7SL RNA
      packaging by overexpression of SRP19 protein inhibited A3F virion packaging.
      Although A3F has been shown to interact with P bodies and viral genomic RNA, our
      data indicated that P bodies and HIV-1 genomic RNA were not required for A3F
      packaging. Thus, in addition to its well-known function in SRPs, 7SL RNA, which
      is encapsidated into diverse retroviruses, also participates in the innate
      antiviral function of host cytidine deaminases.

PMID- 18067919
TI  - The zinc finger and C-terminal domains of MTA proteins are required for FOG-2
      mediated transcriptional repression via the NuRD complex.
AB  - FOG-2 is a transcriptional co-regulator that is required for cardiac
      morphogenesis as mice deficient in this factor die during mid-gestation of
      cardiac malformations. FOG-2 interacts with GATA4 to attenuate GATA4-dependent
      gene expression. The first 12 amino acids of FOG-2 (the FOG Repression Motif) are
      necessary to mediate this repression. To determine the mechanism by which the FOG
      Repression Motif functions, we identified 7 polypeptides from rat cardiac nuclear
      extracts that co-purified with a GST-FOG-2 fusion protein. All proteins
      identified are members of the NuRD nucleosome remodeling complex. Using in vitro
      binding and co-immunoprecipitation assays, we demonstrate that Metastasis
      Associated proteins (MTA)-1, 2 and 3 and Retinoblastoma binding proteins RbAp46
      and RbAp48 interact with FOG-2, but not with a mutant form of FOG-2 that is
      unable to repress transcription. Furthermore, we define a novel domain located in
      the C-terminal portion of MTA-1 that mediates the FOG-2/MTA-1 interaction. We
      also demonstrate that knockdown of MTA protein expression dramatically impairs
      the ability of FOG-2 to repress GATA4 activity. Finally, we show that the zinc
      finger domain of MTA-1 is required for FOG-2-mediated transcriptional repression
      and that this domain interacts with RbAp46 and RbAp48 subunits of the NuRD
      complex. Together, these results demonstrate the importance of FOG-2/MTA/RbAp
      interactions for FOG-2-mediated transcriptional repression and further define the
      molecular interactions between the FOG Repression Motif and the NuRD complex.

PMID- 18067921
TI  - Epistatic interaction between the K-homology domain protein HEK2 and SIR1 at HMR
      and telomeres in yeast.
AB  - In budding yeast, telomeres, the ribosomal DNA array, and HM loci are
      transcriptionally silenced by chromatin complexes containing Sir proteins. Hek2,
      a protein containing three evolutionary conserved RNA-binding K-homology domains,
      was identified as a suppressor of telomeric silencing [telomeric position effect
      (TPE)]. To explore the mechanisms of Hek2p action in gene silencing, we examined
      its relationship with Sir proteins. This search revealed an epistatic interaction
      between HEK2 and SIR1 at telomeres. Both single mutations, sir1Delta and
      hek2Delta, enhanced TPE, whereas the effect of double mutation, sir1Delta
      hek2Delta, did not exceed that of the single mutations. The results of chromatin
      immunoprecipitation analysis demonstrate that the TPE enhancement observed in
      these mutants is associated with increased binding of Sir2 protein to telomeres.
      At the HMR locus, hek2Delta rescues the silencing defect caused by sir1Delta
      mutation and reverses the loss of Sir2p and Sir3p. These data suggest that the
      epistatic interaction of HEK2 and SIR1 reflects competition between telomeres and
      HMR for Sir2/3 factors where HEK2 acts to suppress silencing. Because chromatin
      immunoprecipitation analysis reveals the presence of Hek2p at a subtelomeric
      region and HMR, its silencing effects at these loci are likely direct. These
      observations suggest that HEK2 regulates the composition of Sir complexes at HMR
      and telomeres.

PMID- 18067922
TI  - Remodeling of the human papillomavirus type 11 replication origin into discrete
      nucleoprotein particles and looped structures by the E2 protein.
AB  - The human papillomavirus (HPV) DNA replication origin (ori) shares a common theme
      with many DNA control elements in having multiple binding sites for one or more
      proteins spaced over several hundreds of base pairs. The HPV type 11 ori spans
      103 bp and contains three palindromic E2 binding sites (E2BS-2, E2BS-3, and E2BS
      4) for the dimeric E2 ori binding protein. These sites are separated by 64 and 3
      bp. E2BS-1 is located 288 bp upstream of E2BS-2 and is not required for efficient
      transient or cell-free replication. In this study, electron microscopy was used
      to visualize complexes of HPV-11 DNA ori bound by purified E2 protein. DNA
      containing only E2BS-2 showed a single E2 dimer bound. DNA containing E2BS-3 and
      E2BS-4 showed two side-by-side E2 dimers, while DNA containing E2BS-2, E2BS-3,
      and E2BS-4 exhibited a large disk/ring-shaped protein particle bound, indicating
      that the DNA had been remodeled into a discrete complex, likely containing an E2
      hexamer. With all four binding sites present, up to 27% of the DNA molecules were
      arranged into loops by E2, the majority of which spanned E2BS-1 and one of the
      other three sites. Studies on the dependence of looping on salt, ATP, and DTT
      using full-length E2 and an E2 protein containing only the carboxyl-terminal DNA
      binding and protein dimerization domain suggest that looping is dependent on the
      N-terminal domain and factors that may affect the manner in which E2 scans DNA
      for binding sites. The role of these structures in the modeling and regulation of
      the HPV-11 ori is discussed.

PMID- 18067923
TI  - The role of the new Ca2+ antagonist, CV159, in hepatic I/R injury-the evaluation
      of hepatic organ reducing activity using in vivo and ex vivo EPR.
AB  - We investigated the organ-reducing ability of 1,2-dihydro-2,6-dimethyl-4-(3
      nitrophenyl)-3,5-pyridine-dicarboxylic acid methyl 6-(5-phenyl-3-pyrazolyloxy)
      hexyl ester (CV159) that exhibits selective blocking of Ca(2+)/calmodulin and
      inhibition of Ca(2+) overloading in living organisms (Sprague Dawley rats) using
      an in vivo and an ex vivo electron paramagnetic imaging technique. Decay rates in
      CV159-treated rats were significantly higher than those in untreated rats and
      were almost equal to those in the sham group. Both cytosol and mitochondrial
      superoxide scavenging activity in CV159-treated rats were significantly higher
      than those in untreated rats, and cytosol superoxide scavenging activity only was
      slightly higher than that in the sham group. Faint staining for anti-superoxide
      dismutase antibody was markedly observed in necrotic lesions in the liver of
      control group. Alanine aminotransferase level in CV-treated rats were
      significantly decreased as compared with the levels in untreated rats. Electron
      microscopy showed a decreased number of damaged mitochondria, whereas
      mitochondrial damage was significantly reduced in CV-treated animals. We conclude
      that CV159 retains the organ-reducing activity against radicals in hepatic I/R
      injury that is mediated by the inhibition of Ca(2+) overloading.

PMID- 18067924
TI  - The role of cytoprotective cytokines in cardiac ischemia/reperfusion injury.
AB  - The mechanism(s) underlying the beneficial effects of adult mesenchymal stem
      cells (MSCs) after myocardial infarction (MI) is poorly understood. One possible
      explanation is the ability of MSCs to secrete cytokines, which modulate
      cardiomyocyte survival and function. MSCs express at least two cytoprotective
      cytokines, hepatocyte growth factor (HGF) and stromal cell-derived factor-1 alpha
      (CXCL12). The aim of our study was to compare the effects of these two cytokines
      administered acutely post-MI. We subjected adult male Lewis rats to myocardial
      ischemia/reperfusion injury. Immediately upon reperfusion, polymers saturated
      with HGF or CXCL12 were placed onto the infarcted anterior wall and the rats were
      allowed to recover. Echocardiographic analysis at 4 wk post-MI to assess left
      ventricular (LV) function revealed that LV ejection fraction was increased in the
      HGF treated group compared with the phosphate-buffered saline (PBS) control
      group. Likewise, LV end diastolic dimension was reduced in the HGF treated group
      compared with the PBS control group. Similarly, invasive hemodynamics at 12 wk
      showed improved contractility and relaxation in the HGF treated group compared
      with the PBS control group. In contrast, no significant effect on LV function was
      seen in the CXCL12 treated group. To determine the potential mechanism for this
      effect, infarct size (IFS) at 72 h was determined. IFS was decreased 4.2-fold in
      the HGF treated group compared with the PBS control group. Thus, HGF acutely post
      MI using polymer delivery reduces IFS, leading to beneficial effects on post-MI
      LV remodeling.

PMID- 18067925
TI  - Attenuation of iNOS in an LPS-stimulated macrophage model by omega-3 fatty acids
      is independent of COX-2 derived PGE2.
AB  - BACKGROUND: Omega-3 fatty acids (n-3 FA) demonstrate significant anti
      inflammatory properties thought to occur through three principal mechanisms; (1)
      displacement of arachidonic acid from the cellular membrane, (2) differential
      prostaglandin E2 (PGE2) and LTB4 production, and (3) molecular level alterations
      such as diminished nuclear factor kappa B and AP-1 activation. Recently, n-3 FA
      have been demonstrated to significantly decrease nitric oxide (NO) production in
      a lipopolysaccharide (LPS)-stimulated M Phi model. We hypothesized that decreased
      NO production by n-3 FA occurs through inhibition of cyclooxygenase-2 (COX-2)
      derived PGE2 and that repletion of the system with PGE2 would obliterate these
      effects. Selective COX-2 inhibitor (L-748,731) experiments and separate PGE2
      repletion studies were used to test this hypothesis. METHODS: NO production was
      assessed following 24 h with or without LPS/PGE2 in the presence of n-3 FA, L
      748,731 (a selective COX-2 inhibitor), or combination (n-3 FA + L-748,731)
      treatment. Western blots were used to assess inducible NO synthase protein
      expression. RESULTS: Independently or in the presence of LPS, treatment with a
      COX-2 inhibitor significantly increased NO production compared with control, n-3
      FA, and combination treatment. NO production in combination treatment is slightly
      increased compared to n-3 FA treatment. In control cells treated with LPS, PGE2
      repletion resulted in a significant decrease in NO. All other treatment groups
      repleted with PGE2 demonstrated no significant alterations in NO production.
      Inducible NO synthase protein expression levels were similar to NO production
      across all treatments. CONCLUSION: These experiments disproved our original
      hypothesis that the decrease in NO production associated with n-3 FA treatment
      occurs through a COX-2 derived PGE2 dependent mechanism. Eliminating COX-2
      derived PGE2 by a selective inhibitor actually increased NO production. Exogenous
      PGE2 repletion did not restore the system. Therefore, mechanisms other than n-3
      FA associated alterations in COX-2 derived PGE2 are likely involved in decreasing
      NO production in LPS stimulated M Phi.

PMID- 18067926
TI  - Effect of CV159-Ca(2+)/calmodulin blockade on redox status hepatic ischemia
      reperfusion injury in mice evaluated by a newly developed in vivo EPR imaging
      technique.
AB  - 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 6
      (5-phenyl-3-pyrazolyloxy)hexyl ester (CV159) exhibits selective blocking of
      Ca(2+)/calmodulin and inhibits Ca(2+) overloading in living organisms. The
      effects of this antagonist in mice with hepatic ischemia-reperfusion injury were
      investigated using electron paramagnetic resonance imaging (EPRI) and ex vivo EPR
      (x-band EPR) techniques. The EPRI determined that the 3-carbamoyl-2,2,5,5
      tetramethylpyrrolidine-1-oxyl half-life in CV159-treated mice was significantly
      shorter than that in untreated mice and was almost equal to that in the sham
      group. Both the cytosolic and the mitochondrial superoxide scavenging activities
      in CV-treated mice were significantly higher than that in untreated mice. Faint
      staining of the anti-superoxide dismutase antibody and strong staining of anti
      inducible nitric oxide synthase antibody were observed in the liver of control
      group. In contrast to these findings, immunostaining of these antibodies in the
      liver of CV159-treated mice were reversed compared to control group. Western
      blotting showed that CV159 contributed to the high superoxide dismutase
      expression and low expression of inducible nitric oxide synthase. The alanine
      aminotransferase level in CV159-treated mice significantly decreased in
      comparison to that observed in the untreated mice. We conclude that CV159 retains
      its organ-reducing activity against radicals in hepatic reperfusion injury, which
      is mediated by the inhibition of Ca(2+) overloading.

PMID- 18067927
TI  - Simple computational models of type I/type II cells in Fas signaling-induced
      apoptosis.
AB  - Distinct apoptotic response of the type I/type II cells against Fas-ligand
      stimulation is considered to arise from the difference in dominant signaling
      pathways involved. In the type I cells, apoptotic signaling predominantly takes
      place via the direct activation of caspase-3 by activated caspase-8 (D channel)
      while mitochondrial pathway (M channel) plays a major role in the type II cells.
      To elucidate the selection mechanism of dominant pathway, we carried out
      systematic model analysis of the Fas signaling-induced apoptosis network. An
      increase in the expression level of caspase-8 induced a switch of dominant
      pathway from M- to D-channel (M-D transition), showing a phenotypic change from
      type II to type I cells. With the aid of sensitivity analysis and kinetic
      considerations, we succeeded in constructing a minimal network model relevant for
      the M-D transition, which revealed that mechanistic origin of the transition lies
      in the competition between the activated forms of caspase-8 and caspase-9 for
      their common substrate caspase-3. The pathway dominance was found to be primarily
      controlled by the balance between the activation rate of caspase-8 and the
      initial level of caspase-9. In the full network model, we showed that
      differential formation ability of the death-inducing signaling complex (DISC) can
      also induce M-D transition, in accordance with the experimental observations.

PMID- 18067928
TI  - Genetic polymorphisms in cytochrome P4501B1 and susceptibility to head and neck
      cancer.
AB  - Cytochrome P4501B1 (CYP1B1), a polycyclic aromatic hydrocarbon (PAH) metabolizing
      CYP, is genetically polymorphic in humans and may be involved in the individual
      susceptibility to chemical-induced cancer. In the present study, genotype and
      haplotype frequencies of four single nucleotide polymorphisms (SNPs) in CYP1B1
      that cause amino acid changes (Arg-Gly at codon 48, Ala-Ser at codon 119, Leu-Val
      at codon 432 and Asn-Ser at codon 453) were studied in 150 cases suffering from
      head and neck squamous cell carcinoma (HNSCC) and in an equal number of controls.
      A significant difference was observed for the distribution of variant genotypes
      of Arg48Gly (CYP1B1*2) and Ala119Ser (CYP1B1*2) polymorphisms of CYP1B1 in cases
      versus controls. No significant differences were observed for the distribution of
      variant genotypes-Leu432Val (CYP1B1*3) and Asn453Ser (CYP1B1*4), respectively.
      When the four SNPs were analyzed using a haplotype approach, SNPs at codon 48
      (Arg48Gly) and codon 119 (Ala119Ser) exhibited complete linkage disequilibrium
      (LD) in all the cases and controls. Significant differences in the distribution
      of the two haplotypes (G-T-C-A and G-T-G-A) were observed both in the cases and
      in controls. Furthermore, our data indicates a several fold increase in risk in
      the cases who use tobacco (cigarette smoking or tobacco chewing) or alcohol with
      the variant genotypes of CYP1B1 (CYP1B1*2 and CYP1B1*3) suggesting the role of
      gene-environment interaction in the susceptibility to HNSCC.

PMID- 18067929
TI  - rCBF pathology in Alzheimer's disease is associated with slow processing speed.
AB  - Decreased information processing speed (mental slowing) is a known sequelae of
      many brain disorders, and can be assessed by continuous naming tasks. Functional
      imaging studies have shown that pause and articulation times in continuous speech
      are normally associated with different brain regions, but knowledge about such
      association in dementia is lacking. We therefore tested the hypothesis that
      perfusion deficits in Alzheimer's disease (AD) are not only associated with
      slower processing, but also with these speech measures. Using regional cerebral
      blood flow (rCBF) measurements during the performance of a continuous colour and
      form-naming task, we found that naming speed was substantially slower in AD
      patients than in controls. This slower naming was exclusively determined by an
      increase in mean pause time, and only to a limited extent by articulation time.
      The increased pause time was uniquely associated with temporo-parietal rCBF
      reductions of the patients, while articulation was not. By contrast, the rCBF of
      healthy elderly control subjects was consistently accompanied by substantially
      shorter articulation and pause times, although the naming measures were not
      statistically associated with rCBF. These findings suggest that pause time (in
      contrast to articulation time) may serve as a sensitive measure in the assessment
      of information processing speed deficits in dementia, by virtue of its close
      association with brain pathology.

PMID- 18067930
TI  - Effects of morphine dependence on the performance of rats in reference and
      working versions of the water maze.
AB  - Numerous studies have dealt with the role of opiate system in tasks aimed at
      measurement of cognitive behavior, but the role of morphine dependence on
      learning and memory is still controversial. In this study chronic exposure to
      morphine was employed to evaluate learning ability and spatial short-term memory
      (working memory) and long-term memory (reference memory) in the water maze task.
      Male albino rats were made dependent by chronic administration of morphine in
      drinking water that lasted at least 21 days. In Experiment 1, the performance of
      animals was evaluated in reference memory version of the water maze. Rats were
      submitted to a session of 6 trials for 6 consecutive days to find the submerged
      platform that was located in the center of a quadrant. Latency and traveled
      distance to find the platform were measured as indexes of learning. Memory
      retention was tested 24 h after the last training session in a probe trial (60 s)
      in which there was no platform and the time spent in each quadrant of the water
      maze was recorded. Results indicated that latency and traveled distance to find
      the platform were same in control and dependent rats during training days, but
      during the probe test morphine-dependent group spent significantly less time in
      the target quadrant. In Experiment 2, training on working memory version of the
      water maze task was started. Only two trials per day were given until the
      performance of animals was stabilized (at least 5 days). Final test was done at
      day 6. Acquisition-retention interval was 75 min. No significant differences were
      found on acquisition and retention trials between morphine and control groups.
      Our findings indicate that chronic exposure to morphine did not impair learning
      ability, but partially impaired retention of spatial long-term (reference)
      memory. Moreover, dependence on morphine did not affect either acquisition or
      retention of spatial short (working) memory.

PMID- 18067931
TI  - Anthraquinones from the fruits of Vismia laurentii.
AB  - Phytochemical study of the fruits of Vismia laurentii resulted in the isolation
      of five structurally related compounds. Three of them are constituents, namely,
      laurentiquinone A (1) (methyl 1,6,8-trihydroxy-3-methyl-7-(3-methylbut-2-enyl)
      9,10-dioxo-9,10-dihydroanthracene-2-carboxylate), laurentiquinone B (2) (methyl
      5,7-dihydroxy-2,2,9-trimethyl-6,11-dioxo-6,11-dihydro-2H-anthra[2,3-b]pyran-8
      carboxylate) and laurentiquinone C (3) (methyl 9-(ethanoyloxymethyl)-5,7
      dihydroxy-2,2-dimethyl-6,11-dioxo-6,11-dihydro-2H-anthra[2,3-b]pyran-8
      carboxylate) and two are known compounds, emodin (4) and isoxanthorin (5). Their
      structures were elucidated by spectroscopic means. Crude extracts of hexane and
      EtOAc showed anti-plasmodial activity against the W2 strain of Plasmodium
      falciparum.

PMID- 18067932
TI  - Polyketides from Penicillium sp. JP-1, an endophytic fungus associated with the
      mangrove plant Aegiceras corniculatum.
AB  - Four polyketides, leptosphaerone C (1), penicillenone (2), arugosin I (3) and 9
      demethyl FR-901235 (4), as well as five known compounds, bacillosporin A (5),
      bacillosporin C (6), sequoiamonascin D (7), sequoiatone A (8), and sequoiatone B
      (9) were isolated from the Penicillium sp. JP-1, an endophytic fungus isolated
      from Aegiceras corniculatum. Their structures were determined by spectroscopic
      methods, mainly by 2D NMR spectroscopic analyses. Compound 1 showed cytotoxicity
      against A-549 cells with an IC50 value of 1.45 microM, while compound 2 showed
      cytotoxicity against P388 cells with an IC50 value of 1.38 microM.

PMID- 18067933
TI  - Embryonic development of the histaminergic system in the ventral nerve cord of
      the Marbled Crayfish (Marmorkrebs).
AB  - The embryonic development of neurotransmitter systems in crustaceans so far is
      poorly understood. Therefore, in the current study we monitored the ontogeny of
      histamine-immunoreactive neurons in the ventral nerve cord of the Marbled
      Crayfish, an emerging crustacean model system for developmental studies. The
      first histaminergic neurons arise around 60% of embryonic development, well after
      the primordial axonal scaffold of the ventral nerve cord has been established.
      This suggests that histaminergic neurons do not serve as pioneer neurons but that
      their axons follow well established axonal tracts. The developmental sequence of
      the different types of histaminergic neurons is charted in this study. The
      analysis of the histaminergic structures is also extended into adult specimens,
      showing a persistence of embryonic histaminergic neurons into adulthood. Our data
      are compared to the pattern of histaminergic neurons in other crustaceans and
      discussed with regard to our knowledge on other aspects of neurogenesis in
      Crustacea. Furthermore, the possible role of histaminergic neurons as characters
      in evolutionary considerations is evaluated.

PMID- 18067934
TI  - Circulating hemocytes from larvae of the paper wasp Polistes dominulus
      (Hymenoptera, Vespidae).
AB  - Circulating hemocytes from larval stages of the paper wasp Polistes dominulus
      were characterized by light and transmission electron microscopy. Three types
      were identified: prohemocytes, plasmatocytes and granulocytes. The first two are
      agranular cells while the latter present typical cytoplasmic inclusions called
      granules. Plasmatocytes differ from prohemocytes being larger, showing lower
      nucleus/cytoplasm ratio and they possess many phagolysosomes. The substantial
      uniformity of most subcellular features and the presence of "intermediate forms"
      support the "single-cell theory" i.e., there is only one cell line that
      originates from the prohemocyte and leads to the granular cell passing through
      the plasmatocyte. This hypothesis seems to be confirmed by functional tests.
      Indeed, most part of cells adheres to the glass and is able to phagocytize
      fluorescent microspheres.

PMID- 18067935
TI  - Microcystin accumulation in liver and muscle of tilapia in two large Brazilian
      hydroelectric reservoirs.
AB  - The objective of this study was to measure levels of the toxin microcystin in
      different tissues of fish known to feed on cyanobacteria during toxic bloom
      events. Wild Nile and redbreast tilapia (Oreochromis niloticus and Tilapia
      rendalli) were sampled from the catch of artisanal fishermen at eutrophic
      stations of Funil and Furnas reservoirs in southeastern Brazil. Phytoplankton
      communities in the two reservoirs were quite different taxonomically, but not
      dissimilar in microcystin content (200 microg g dry weight (DW) seston(-1) at
      Funil, 800 microg gDW seston(-1) at Furnas). All of the 27 fish sampled contained
      microcystin, ranging from 0.8 to 32.1 microg g liver(-1) and from 0.9 to 12.0 ng
      g muscle(-1). Most microcystin variants found in seston were also found in fish
      liver. T. rendalli had the lowest concentration in both tissues when compared to
      O. niloticus. In both reservoirs, one of every four fish sampled, always O.
      niloticus, had a level of microcystins beyond the World Health Organization
      tolerable daily intake (8 ng g tissue(-1)) and represented a risk for consumers.
      It is possible that closer study of inter-species variability in toxin burden in
      cyanobacteria-impacted water bodies will permit the development of guidelines for
      fish consumption that will better protect public health.

PMID- 18067936
TI  - Topology and enhanced toxicity of bound microcystins in Microcystis PCC 7806.
AB  - The cyanobacterium Microcystis is a potent producer of microcystins and
      cyanopeptolins and causes most of the toxicity outbreaks in freshwaters
      worldwide. Microcystins are mainly stored in the cells and little is found in the
      water. The intracellular concentration of microcystins in Microcystis PCC 7806
      was at least 0.9 mM, although the solubility of microcystins in water was only
      about 10 microM. This low solubility does not allow the solubilisation of such
      high amounts of microcystins in the cytosol of Microcystis. Differential
      fractionation of cell constituents showed that microcystins and cyanopeptolins
      were bound to a protein fraction primarily composed of phycobilins. The
      percentage of microcystins and cyanopeptolins found in the thylakoid membranes
      was very low. Phycobilins may be the major proteins that have binding sites for
      these oligopeptides. A molar ratio near to 6 was observed for microcystins to the
      phycobilin (alphabeta) monomer. The binding of the microcystins to the protein
      was rather weak and allowed rapid dissociation of microcystins from the protein
      matrix. Toxicity assays with Thamnocephalus platyurus showed that native
      microcystin when still bound to cyanobacterial protein was more toxic than an
      equivalent amount that has been desorbed from the protein by treatment with
      methanol. It is suggested that phycobilins serve in the gut of grazers as carrier
      molecules for the rapid transport of microcystin from lysed cells of Microcystis
      to the epithelium where the uptake of microcystins occurs. Because protein-bound
      microcystin does not bind to C18 cartridges, this behaviour can be the cause of
      many analytical discrepancies observed. The blue-coloured water observed upon the
      collapse of Microcystis blooms may be extremely toxic because the released
      phycobilins may carry the major fraction of microcystins.

PMID- 18067937
TI  - Effects of seawater on growth and gliotoxin excretion of marine strains of
      Aspergillus fumigatus Fres.
AB  - In order to enhance the knowledge of the putative toxinic risk linked to
      mycotoxin excretion in shellfish farming areas, the influence of seawater
      salinity was studied on 2 marine-derived Aspergillus fumigatus strains. This
      fungal species produces gliotoxin, an epipolythiodioxopiperazine
      immunosuppressive mycotoxin that can be accumulated in the meat of cultured blue
      mussel (Mytilus edulis), and could be responsible for disease when ingested. Two
      marine strains were grown in vitro both on a non-saline and a saline culture
      media and were compared with 13 terrestrial strains to observe the effects of
      seawater on fungal growth and gliotoxin excretion in the exudate produced. Daily
      measurement of the colony areas showed that the seawater salinity significantly
      reduced the rate of growth of all the strains. Marine and terrestrial strains
      appeared to be almost similar as regards the appearance, growth and gliotoxin
      excretion, but the marine strains exudation seemed to be less influenced by
      seawater salinity than the terrestrial strains. Seawater salinity, however,
      enhanced exudation and gliotoxin excretion by A. fumigatus, and thus seems to be
      an aggravating factor for the toxicity of this species in the marine environment.

PMID- 18067938
TI  - First episode of shellfish contamination by palytoxin-like compounds from
      Ostreopsis species (Aegean Sea, Greece).
AB  - In order to investigate the toxicity of Ostreopsis species present in Greek
      coastal waters, cultures of Ostreopsis sp. and Ostreopsis ovata, mixed Ostreopsis
      field populations and shellfish collected from coastal waters of North Aegean Sea
      during late summer and autumn periods of 2004, 2005 and 2006 were examined by
      both mouse bioassay (MBA) and hemolysis neutralization assay (HNA). MBA testing
      was based on two different extraction protocols, while HNA also included the use
      of ouabain, a known palytoxin (PLT) antagonist. Results indicated the presence of
      a compound in both Ostreopsis cells and shellfish tissues, which was strongly
      toxic to mice. This compound exhibited characteristic symptomatology in mice
      (death, numbness, waddling gait and blindness) to that of PLT, as well as delayed
      hemolytic activity, which was neutralized by ouabain. HNA indicated that
      Ostreopsis cells contained a PLT-like compound (putative PLT, p-PLT) at
      concentrations ranging between 0.4 and 0.9 pg/cell, whereas concentration in
      shellfish tissues was estimated to range from about 33.3 to 97.0 microg p-PLT/kg
      tissue. To our knowledge, this is the first report of p-PLT contamination of
      shellfish by natural Ostreopsis species populations in European coastal waters
      and possibly globally, and also the first evidence on Ostreopsis cells' toxicity
      in the Eastern Mediterranean Sea.

PMID- 18067939
TI  - Two critical residues in p-loop regions of puffer fish Na+ channels on TTX
      sensitivity.
AB  - We previously showed that Asn-383 and Thr-1569 residues of p-loop regions in
      domains I and IV, respectively, of the puffer fish, Fugu pardialis, skeletal
      muscle Na(v) (fNa(v)1.4a), are anomalous to those of other species of TTX
      sensitive Na(+) channels, where the aromatic residues of Phe or Tyr, and Gly are
      the counterparts [Yotsu-Yamashita, M., Nishimori, K., Nitanai, Y., Isemura, M.,
      Sugimoto, A., Yasumoto, T., 2000. Binding properties of (3)H-PbTx-3 and (3)H
      saxitoxin to brain membranes and to skeletal muscle membranes of puffer fish Fugu
      pardalis and the primary structure of a voltage-gated Na(+) channel alpha-subunit
      (fMNa1) from skeletal muscle of F. pardalis. Biochem. Biophys. Res. Commun. 267,
      403-412]. The former was suggested to confer TTX resistance by using Y401N mutant
      of rNa(v)1.4 [Venkatesh, V., Lu, S.Q., Dandona, N., See, S.L., Benner, S., Soong,
      T.W., 2005. Genetic basis of tetrodotoxin resistance in pufferfishes. Curr. Biol.
      15, 2069-2072]. The latter function remained to be elucidated. Thus, we further
      explored the function of these two residues, electrophysiologically, by
      evaluating the K(d) (dissociation constants) values of TTX for F385N, F385A,
      F385Q, G1718T, and F385N/G1718T mutants of rNa(v)1.2a, transiently expressed in
      HEK-293 cells. F385N caused 3000-fold increase of the K(d), while G1718T and
      F385N/G1718T caused 2- and 3-fold increases compared with those of WT and F385N,
      respectively, suggesting that G1718T further enhanced TTX resistivity caused by
      F385N. The K(d) for F385A and F385Q were 2- and 11-fold larger than that of
      F385N, respectively, suggesting that the longer side chain in the non-aromatic
      amino acid residue causes the larger decrease of TTX sensitivity. Despite drastic
      changes in the K(d), the mutations at F385 caused only small changes in the
      k(off) from that of WT, suggesting that the K(d) for TTX receptors are mainly
      determined by the k(on).

PMID- 18067940
TI  - Stability of alteplase in presence of cavitation.
AB  - Several experimental studies have demonstrated that ultrasound (US) can
      accelerate enzymatic fibrinolysis and this effect is further enhanced in the
      presence of ultrasound contrast agents (UCA). Although UCA have been shown to be
      safe when administered to ischemic stroke patients, safety information of these
      agents in the thrombolysis setting is limited. Therefore, in this study we
      investigated potential adverse effects of acoustic cavitation generated by UCA on
      alteplase (t-PA), the drug used for treatment of ischemic stroke patients. A
      volume of 0.9 mL of alteplase was dispensed into a custom-made polyester sample
      tube. For treatments in the presence or absence of cavitation either 0.1 mL
      Optison or phosphate buffer saline was combined with alteplase. Three independent
      samples of each treatment group were exposed to ultrasound of 2 MHz frequency at
      three different peak negative acoustic pressures of 0.5, 1.7, and 3.5 MPa for a
      duration of 60 min. All treatments were carried out in a cavitation detection
      system which was used to insonify the samples and record acoustic emissions
      generated within the sample. After ultrasound exposure, the treated samples and
      three untreated drug samples were tested for their enzymatic activity using a
      chromogenic substrate. The insonified samples containing Optison demonstrated
      cavitational activity proportional to acoustic pressure. No significant
      cavitation activity was observed in the absence of Optison. Enzymatic activity of
      alteplase in both insonified groups was comparable to that in the control group.
      These tests demonstrated that exposure of alteplase to 60 min of 2 MHz ultrasound
      at acoustic pressures ranging from 0.5 MPa to 3.5 MPa, in the presence or absence
      of Optison had no adverse effects on the stability of this therapeutic compound.

PMID- 18067941
TI  - The Rayleigh-Plesset equation in terms of volume with explicit shear losses.
AB  - The most common nonlinear equation of motion for the damped pulsation of a
      spherical gas bubble in an infinite body of liquid is the Rayleigh-Plesset
      equation, expressed in terms of the dependency of the bubble radius on the
      conditions pertaining in the gas and liquid (the so-called 'radius frame').
      However over the past few decades several important analyses have been based on a
      heuristically derived small-amplitude expansion of the Rayleigh-Plesset equation
      which considers the bubble volume, instead of the radius, as the parameter of
      interest, and for which the dissipation term is not derived from first
      principles. So common is the use of this equation in some fields that the
      inherent differences between it and the 'radius frame' Rayleigh-Plesset equation
      are not emphasised, and it is important in comparing the results of the two
      equations to understand that they differ both in terms of damping, and in the
      extent to which they neglect higher order terms. This paper highlights these
      differences. Furthermore, it derives a 'volume frame' version of the Rayleigh
      Plesset equation which contains exactly the same basic physics for dissipation,
      and retains terms to the same high order, as does the 'radius frame' Rayleigh
      Plesset equation. Use of this equation will allow like-with-like comparisons
      between predictions in the two frames.

PMID- 18067942
TI  - The E7 protein of the cottontail rabbit papillomavirus immortalizes normal rabbit
      keratinocytes and reduces pRb levels, while E6 cooperates in immortalization but
      neither degrades p53 nor binds E6AP.
AB  - Human papillomaviruses (HPVs) cause cervical cancer and are associated with the
      development of non-melanoma skin cancer. A suitable animal model for
      papillomavirus-associated skin carcinogenesis is the infection of domestic
      rabbits with the cottontail rabbit papillomavirus (CRPV). As the immortalizing
      activity of CRPV genes in the natural target cells remains unknown, we
      investigated the properties of CRPV E6 and E7 in rabbit keratinocytes (RK) and
      their influence on the cell cycle. Interestingly, CRPV E7 immortalized RK after a
      cellular crisis but showed no such activity in human keratinocytes. Co-expressed
      CRPV E6 prevented cellular crisis. The HPV16 or CRPV E7 protein reduced rabbit
      pRb levels thereby causing rabbit p19(ARF) induction and accumulation of p53
      without affecting cellular proliferation. Both CRPV E6 proteins failed to degrade
      rabbit p53 in vitro or to bind E6AP; however, p53 was still inducible by
      mitomycin C. In summary, CRPV E7 immortalizes rabbit keratinocytes in a species
      specific manner and E6 contributes to immortalization without directly affecting
      p53.

PMID- 18067943
TI  - Retinal and cortical patterns of spatial anisotropy in contrast sensitivity
      tasks.
AB  - It has often been postulated that asymmetries in performance within the visual
      field (VF) are not characteristic of early visual processing. Here, human retinal
      (naso/temporal), cortical (left/right) and superior/inferior patterns of
      asymmetry were explored with achromatic contrast sensitivity (CS) tasks, that
      probed distinct spatiotemporal frequency channels. Low spatial, high temporal
      frequency stimuli (illusory frequency-doubling (FD)) yielded superior and
      temporal field disadvantage. Independent right and nasal visual hemifield
      patterns of disadvantage were found when probing an intermediate spatial
      frequency (ISF) channel, with stationary sinusoidal gratings. These findings show
      that asymmetries in spatial vision are explained by independent retinal and
      cortical mechanisms.

PMID- 18067944
TI  - Estimation of nitrate reductase enzyme parameters in activated sludge using an
      extended Kalman filter algorithm.
AB  - This paper demonstrates an application of the extended Kalman filter to a
      wastewater plant using real process data to estimate parameters in a semi
      mechanistic model. This technique for parameter identification allows a semi
      mechanistic model developed for pure cultures to be applied to a mixed culture
      population where isolation of enzyme kinetic parameters is not practical. This
      paper demonstrates an application in which a wastewater treatment facility with
      three physical unit operations and an unusual operating profile is modeled as 11
      reactor units with recirculation streams. On-line nutrient probe data from two
      locations in the aerobic reactor are combined with operational data for flows and
      feed composition. This paper demonstrates the successful application of a
      biochemical model developed at the bench scale to this facility through the use
      of an extended Kalman filter. The estimated biological model parameters and the
      covariance matrix diagonal converge to stable values, indicating a successful
      implementation.

PMID- 18067945
TI  - Effect of water treatment processes on Cryptosporidium infectivity.
AB  - Conventional water treatment processes have the ability to remove Cryptosporidium
      oocysts through coagulation, flocculation, sedimentation and filtration, provided
      there is efficient management of plant performance. The potential exists for the
      breakthrough of oocysts through the treatment train. The effect of the water
      treatment chemical aluminium sulphate (alum) on Cryptosporidium oocyst
      infectivity has been assessed using an assay that combines cell culture and real
      time polymerase chain reaction techniques. The infectivity of fresh and
      temperature-aged oocysts (stored up to 6 months at 4 or 15 degrees C) was
      unaffected by exposure to a range of doses of alum in standard jar test
      procedures and dissolved air flotation processes and subsequent exposure to
      chlorine or chloramine. Removal efficiencies and infectivity measures are
      important in determining risk to public health and will reflect the ability of
      water treatment plants to act as a barrier to these pathogens.

PMID- 18067946
TI  - Partitioning of hydrophobic organic compounds within soil-water-surfactant
      systems.
AB  - Understanding the partitioning of hydrophobic organic compounds (HOCs) within
      soil-water-surfactant systems is key to improving the use of surfactants for
      remediation. The overall objective of this study was to investigate the soil
      properties that influence the effectiveness of surfactants used to remediate soil
      contaminated with hydrophobic pesticides, as an example of a more general
      application for removing strongly sorbing HOCs from contaminated soils via in
      situ enhanced sorption, or ex-situ soil washing. In this study, the partitioning
      of two commonly used pesticides, atrazine and diuron, within soil-water
      surfactant systems was investigated. Five natural soils, one nonionic surfactant
      (Triton-100 (TX)) and one cationic surfactant (benzalkonium chloride (BC)) were
      used. The results showed that the cation exchange capacity (CEC) is the soil
      property that controls surfactant sorption onto the soils. Diuron showed much
      higher solubility enhancement than atrazine with the micelles of either
      surfactant. Within an ex-situ soil washing system, TX is more effective for soils
      with lower CEC than those with higher CEC. Within an in-situ enhanced sorption
      zone, BC works significantly better with more hydrophobic HOCs. The HOC sorption
      capacity of the sorbed surfactant (K(ss)) was a non-linear function of the amount
      of surfactant sorbed. For the cationic surfactant (BC), the maximal K(ss)
      occurred when around 40% of the total CEC sites in the various soils were
      occupied by sorbed surfactant. Below a sub-saturation sorption range (~20 g/kg),
      under the same amount of BC sorbed, a soil with lower CEC tends to have higher
      K(ss) than the one with higher CEC.

PMID- 18067947
TI  - Protein extraction from activated sludge: an analytical approach.
AB  - To investigate the efficiency of different methods on exopolymeric substance
      (EPS) extraction, mechanical and chemical treatments were applied on two
      activated sludges, regarding the yield of protein extraction as well as their
      compatibility with usual quantification methods. Mechanical disruption methods do
      not drastically affect protein measurements by both bicinchoninic acid (BCA) and
      modified Lowry methods. Chemical compounds such as cationic exchange resin and
      triton show high interference with modified Lowry method while the protein
      quantification by BCA method is not affected. In addition, inner sludge compounds
      were shown to interfere with both methods: BCA and modified Lowry measurement
      respectively overestimate and underestimate protein content. According to these
      data, BCA method was chosen in this study as the most appropriate protein
      quantification method in sludge extracts. Comparison of various extraction
      protocols, combining mechanical and/or chemical treatments, shows that efficiency
      can be increased by repeating the same method or by applying a prior mechanical
      treatment. Proteins are preferably extracted by triton treatments, indicating the
      importance of hydrophobic interactions linking proteins to the EPS matrix. The
      amount of extracted proteins reaches 182 and 148 mg eq.BSA g(-1)VSS using
      triton/triton and ultraturax/triton extractions, respectively. Protease
      activity/extracted protein ratios vary widely depending on extraction protocols.
      Protease seemed to be preferably extracted by ultrasound and triton treatments
      (150-220 U mg(-1)protein). This study underlines that the choice of a relevant
      coupled quantification/extraction method is of great importance for efficient EPS
      determination.

PMID- 18067948
TI  - Comparison of GC and LC determinations of hexabromocyclododecane in biological
      samples - results from two interlaboratory comparison studies.
AB  - In order to assess the quality and comparability of results from determinations
      of 1,2,5,6,9,10-hexabromocyclododecane (HBCD) in biological samples, two
      interlaboratory comparison studies have been organized. Up to 13 laboratories
      determined either the total HBCD concentration, or concentrations of alpha-, beta
      and gamma-HBCD, or both in cod liver oil, herring filet, salmon filet, butter
      and chicken meat. The laboratories were able to determine total HBCD
      concentrations in the marine samples with satisfying quality (RSD <35%). However,
      the analysis of samples with low HBCD contamination (<about 2ngg(-1) lipid
      weight) should be improved. No statistically significant differences were found
      between total HBCD concentrations obtained by LC-MS and GC-MS. To our knowledge,
      this is the first report on interlaboratory comparison studies concerning the
      determination of HBCD in biological samples comprising results from a sufficient
      number of participants to perform a statistical evaluation.

PMID- 18067949
TI  - Mobilization of Cr(VI) from chromite ore processing residue through acid
      treatment.
AB  - Batch leaching studies on chromite ore processing residue (COPR) were performed
      using acids to investigate leaching of hexavalent chromium, Cr(VI), with respect
      to particle size, reaction time, and type of acid (HNO(3) and H(2)SO(4)). Aqueous
      Cr(VI) is maximized at approximately 0.04 mol Cr(VI) per kg of dry COPR at pH 7.6
      8.1. Cr(VI) mobilized more slowly for larger particles, and the pH increased with
      time and increased more rapidly for smaller particles, suggesting that rate
      limitations occur in the solid phase. With H(2)SO(4), the pH stabilized at a
      higher value (8.8 for H(2)SO(4) vs. 8.0 for HNO(3)) and more rapidly (16 h vs. 30
      h), and the differences in pH for different particle sizes were smaller. The acid
      neutralization capacity (ANC) of COPR is very large (8 mol HNO(3) per kg of dry
      COPR for a stable eluate pH of 7.5). Changes to the elemental and mineralogical
      composition and distribution in COPR particles after mixing with acid indicate
      that Cr(VI)-bearing solids dissolved. However, concentrations of Cr(VI) >2800 mg
      kg(-1) (>50% of the pre-treatment concentration) were still found after mixing
      with acid, regardless of the particle size, reaction time, or type of acid used.
      The residual Cr(VI) appears to be partially associated with poorly-ordered Fe and
      Al oxyhydroxides that precipitated in the interstitial areas of COPR particles.
      Remediation strategies that use HNO(3) or H(2)SO(4) to neutralize COPR or to
      maximize Cr(VI) in solution are likely to require extensive amounts of acid, may
      not mobilize all of the Cr(VI), and may require extended contact time, even under
      well-mixed conditions.

PMID- 18067950
TI  - Spatial and temporal variation of BTEX in the urban atmosphere of Delhi, India.
AB  - Benzene, toluene, ethylbenzene and xylene (BTEX) form an important group of
      aromatic Volatile Organic Compounds (VOCs) because of their role in the
      tropospheric chemistry and the risk posed by them to human health. Concentrations
      of BTEX were determined at different sampling points in the ambient air of Delhi
      in order to investigate their temporal and spatial distributions. Significant
      positive correlation coefficient (p<0.01) was found between inter-species
      concentrations at all the sampling locations. Inter-species ratio and Pearson's
      correlations indicate that gasoline vehicular exhaust could be the major source
      of BTEX in Delhi. The inter-species ratios exhibit clear seasonal variations
      indicating differential reactivity of the VOC species in different seasons.
      Xylenes were found the largest contributor to the ozone formation followed by
      toluene.

PMID- 18067951
TI  - Our changing atmosphere: evidence based on long-term infrared solar observations
      at the Jungfraujoch since 1950.
AB  - The Institute of Astrophysics of the University of Liege has been present at the
      High Altitude Research Station Jungfraujoch, Switzerland, since the late 1940s,
      to perform spectrometric solar observations under dry and weakly polluted high
      mountain conditions. Several solar atlases of photometric quality, extending
      altogether from the near-ultra-violet to the middle-infrared, were produced
      between 1956 and 1994, first with grating spectrometers then with Fourier
      transform instruments. During the early 1970s, scientific concerns emerged about
      atmospheric composition changes likely to set in as a consequence of the growing
      usage of nitrogen-containing agricultural fertilisers and the industrial
      production of chlorine-bearing compounds such as the chlorofluorocarbons and
      hydro-chlorofluorocarbons. Resulting releases to the atmosphere with ensuing
      photolysis in the stratosphere and catalytic depletion of the protective ozone
      layer prompted a worldwide consortium of chemical manufacturing companies to
      solicit the Liege group to help in clarifying these concerns by undertaking
      specific observations with its existing Jungfraujoch instrumentation. The
      following pages evoke the main steps that led from quasi full sun-oriented
      studies to priority investigations of the Earth's atmosphere, in support of both
      the Montreal and the Kyoto Protocols.

PMID- 18067952
TI  - Changes in tissue factor and the effects of tissue factor pathway inhibitor on
      transient focal cerebral ischemia in rats.
AB  - INTRODUCTION: To determine the contribution of tissue factor (TF) to focal
      cerebral ischemia/reperfusion injury, we investigated the changes in TF in rat
      brains with transient focal cerebral ischemia and also assessed the effect of TF
      pathway inhibitor (TFPI). MATERIALS AND METHODS: Spontaneous hypertensive rats
      were subjected to 90-min of middle cerebral artery occlusion (MCAO) and then were
      reperfused for up to 24 h. Immediately after MCAO, recombinant human TFPI
      (rhTFPI) (50 or 20 microg/kg/min) was administered by means of a continuous
      intravenous injection for 4.5 h. RESULTS AND CONCLUSIONS: TF immunoreactivity
      decreased or scattered in the ischemic area after reperfusion, however, an
      increased TF expression was observed in the microvasculature with the surrounding
      brain parenchyma and it peaked at 3 to 6 h, which coincided with the start of
      fibrin formation. On the other hand, total TF protein in ischemic area continued
      to exist and did not remarkably change until 24 h after reperfusion. At 24 h
      after reperfusion, the total infarct volume in the group treated with 50
      microg/kg/min rhTFPI was significantly smaller than that in the controls
      (saline). Western blotting and immunohistochemical studies showed that rhTFPI
      treatment resulted in a decrease of fibrin in the ischemic brains and
      microvasculature. TF-mediated microvascular thrombosis is thus considered to
      contribute to focal cerebral ischemia/reperfusion injury. The continuous infusion
      of rhTFPI until a peak of TF-mediated microvascular thrombosis therefore
      attenuates the infarct volume by reducing fibrin deposition in the cerebral
      microcirculation.

PMID- 18067953
TI  - Numerical simulation of a stroke: computational problems and methodology.
AB  - We discuss the difficulties of the numerical simulation of a stroke, and we
      describe the numerical methods which we have developed and used to obtain some
      realistic results. Nowadays, the computations are performed in two-dimensional
      slices of a brain, but the strategies to obtain full three-dimensional
      simulations are explored. This paper is written so as to be understandable by non
      mathematicians.

PMID- 18067954
TI  - Corticosteroid hormones in the central stress response: quick-and-slow.
AB  - Recent evidence shows that corticosteroid hormones exert rapid non-genomic
      effects on neurons in the hypothalamus and the hippocampal CA1 region. The latter
      depend on classical mineralocorticoid receptors which are accessible from the
      outside of the plasma membrane and display a 10-fold lower affinity for
      corticosterone than the nuclear version involved in neuroprotection.
      Consequently, this 'membrane' receptor could play an important role while
      corticosteroid levels are high, i.e. during the initial phase of the stress
      response. We propose that during this phase corticosterone promotes hippocampal
      excitability and amplifies the effect of other stress hormones. These permissive
      non-genomic effects may contribute to fast behavioral effects and encoding of
      stress-related information. The fast effects are complemented by slower
      glucocorticoid receptor-mediated effects which facilitate suppression of
      temporary raised excitability, recovery from the stressful experience and storage
      of information for future use.

PMID- 18067955
TI  - Activation of the serotonin 5-HT2C receptor is involved in the enhanced anxiety
      in rats after single-prolonged stress.
AB  - We have recently confirmed that exposure of rats to the single-prolonged stress
      (SPS) paradigm induces enhanced hypothalamic-pituitary-adrenal (HPA) axis
      negative feedback and enhanced anxiety, and found that these changes develop time
      dependently following stress exposure, suggesting that it could model the
      neuroendocrinological and behavioral abnormalities of the post-traumatic stress
      disorder (PTSD) patients. In the present study, microarray analysis was performed
      using RNA from the hippocampus, amygdala and anterior cingulate cortex of SPS
      rats and unstressed controls to unveil the molecular changes underlying SPS
      induced behavioral changes. Thirty-one genes were found whose time course of
      expression corresponded to that of behavioral changes. One gene, 5
      hydroxytryptamine2C (5-HT2C) receptor, was identified as a putative candidate.
      The overexpression of the gene in the amygdala of SPS rats was confirmed using
      real-time PCR 7 days after the SPS exposure. This molecule was then
      pharmacologically validated using FR260010 (N-[3-(4-methyl-1H-imidazol-1
      yl)phenyl]-5,6-dihydrobenzo[h]quinazolin-4-amine dimethanesulfonate), a selective
      5-HT2C receptor antagonist. FR260010 (1-10 mg/kg, s.c.) significantly inhibited
      the enhancement of anxiety in SPS rats. These results demonstrate for the first
      time that activation of the brain 5-HT2C receptor is involved in the development
      of behavioral abnormality in this model. This suggests that selective 5-HT2C
      receptor antagonists might provide novel therapeutic avenues for PTSD treatment.

PMID- 18067956
TI  - Autoimmune liver disease 2007.
AB  - Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises
      both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary
      cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap"
      syndromes where hepatitic and cholestatic damage coexists. All these diseases are
      characterized by an extremely high heterogeneity of presentation, varying from
      asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms
      such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The
      detection and characterization of non organ specific autoantibodies plays a major
      role in the diagnostic approach of autoimmune liver disease; anti nuclear
      reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver
      kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the
      serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are
      associated with PBC, while no specific marker is found in PSC, since
      anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA
      or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases.
      Treatment options rely on immunosoppressive therapy (steroids and azathioprine)
      in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these
      diseases liver transplantation remains the only therapeutical approach for the
      end stage of liver disease.

PMID- 18067957
TI  - Chronic HBV-related liver disease.
AB  - Thirty years after its discovery, the hepatitis B virus (HBV) still remains a
      major global public health problem. Worldwide, two billion subjects have been
      infected, 300 million have a chronic infection and more than 600,000 die annually
      of HBV-related liver disease or hepatocellular carcinoma; new infections occur
      because of the presence of a large reservoir of chronic carriers of the virus.
      The knowledge of the HBV organization and replication cycle and the availability
      of sensitive HBV-DNA assays have led to remarkable progress in our understanding
      of the natural history of chronic hepatitis B infections. Crucial to the
      prevention of new infections, to the management and the monitoring of HBV
      carriers and to the choice of best treatment strategy, is the understanding of
      the natural dynamism of HBV infection and of the virus-host interactions that
      induce liver damage.

PMID- 18067958
TI  - QSPR analysis of air-to-blood distribution of volatile organic compounds.
AB  - Quantitative structure property relationship (QSPR) models for the prediction of
      human blood:air partition coefficient (log K(blood)) of volatile organic
      compounds (VOCs) has been developed based on the linear heuristic method (HM) and
      non-linear radial basis function neural networks (RBFNNs). Molecular descriptors
      that are calculated from the structures alone were used to represent the
      characteristics of the compounds. HM was used both to pre-select the whole
      descriptor sets and to build the linear model. RBFNN was performed to obtain more
      accurate models. Both the linear and the non-linear models can give very
      satisfactory prediction results: the correlation coefficient R was 0.964 and
      0.979, and the root-mean-square (RMS) error was 0.3303 and 0.2542 for the whole
      data set, respectively. The prediction result of the non-linear model is better
      than that obtained by the linear model. In addition, this paper provides an
      effective method for predicting log K(blood) from its structures and gives some
      insight into the structural features related to the solubility of VOCs in human
      blood.

PMID- 18067959
TI  - Leaching risk of N-nitrosodimethylamine (NDMA) in soil receiving reclaimed
      wastewater.
AB  - N-nitrosodimethylamine (NDMA) is a potential carcinogen frequently found in
      treated wastewater as a byproduct of chlorination. The potential for NDMA to
      contaminate the groundwater is a significant concern. A solute fate and transport
      model, Hydrus-1D, was used to evaluate the leaching potential of NDMA under
      different irrigation practices and soil properties. The results indicate that the
      risk of NDMA to reach the ground water is slim, when the reclaimed wastewater is
      applied under the customary conditions for landscape irrigation. The NDMA
      disappears in the reclaimed wastewater receiving soils rapidly through the
      microbial degradation and the volatilization processes. The factors that enhance
      the leaching risk are the soil hydraulic conductivity, the NDMA adsorption
      constants, and the irrigation intensity. When the hydraulic conductivity of soil
      is high, the NDMA adsorption constant of soil is low and/or the irrigation
      intensity is high, the NDMA leaching risk may dramatically increase. To reduce
      the NDMA leaching risk, it is imperative that the fields be irrigated at the
      proper volume and frequency and attention be paid to fields with soils having
      high-hydraulic conductivities and/or low-NDMA adsorption constants.

PMID- 18067960
TI  - Development of an assay for testing the antimicrobial activity of skin peptides
      against the amphibian chytrid fungus (Batrachochytrium dendrobatidis) using
      Xenopus laevis.
AB  - This report describes the preliminary characterization of a bioassay for testing
      the antimicrobial activity of amphibian skin peptides against the chytrid fungus,
      Batrachochytrium dendrobatidis. Peptide secretions from Xenopus laevis were
      induced by subcutaneous injections of norepinephrine. Partially purified
      secretions were quantified and incubated at various dilutions with 10(7) cells/mL
      of freshly isolated zoospores for 7 days. Peptide bioactivity was measured as
      cell growth inhibition over the incubation period. The concentration that
      inhibited growth by 80% or greater (IC(80)), based on the linear portion of the
      growth curve, averaged 457+/-158 microg/mL. Growth curve slopes of best-fit line
      equations for individual samples were less variable within control groups than
      the average IC(80) value, and are viewed as a more reliable indicator of peptide
      mixture bioactivity. This assay may be useful for evaluating the impact of
      environmental chemicals on amphibian host resistance to potentially lethal skin
      infections.

PMID- 18067962
TI  - The relationship of macular thickness to clinically graded diabetic retinopathy
      severity in eyes without clinically detected diabetic macular edema.
AB  - PURPOSE: To examine the relationship of optical coherence tomography (OCT)
      measured macular thickness to retinopathy severity in patients with diabetes and
      no clinically detectable macular edema. DESIGN: Retrospective observational case
      series. PARTICIPANTS: Three hundred eighty-three eyes of 383 patients of a
      private retina practice; including 100 normal eyes of patients without diabetes,
      100 eyes of diabetics without retinopathy, 100 eyes of diabetics with mild to
      moderate retinopathy, 35 eyes of diabetics with severe nonproliferative or
      proliferative retinopathy, and 48 eyes of diabetics with regressed proliferative
      retinopathy. METHODS: Review of clinical charts and optical coherence tomography
      measurements. MAIN OUTCOME MEASURES: Central subfield mean thickness (CSMT),
      inner and outer zone measurements, and total macular volume. RESULTS: Central
      subfield mean thicknesses (mean +/- standard deviation) were 208+/-22, 198+/-25,
      204+/-26, 224+/-38, and 205+/-27 microm for normals, eyes of diabetics without
      retinopathy, eyes with mild to moderate nonproliferative retinopathy, eyes with
      severe nonproliferative to proliferative retinopathy, and eyes with regressed
      proliferative retinopathy, respectively. For all groups, mean CSMT was larger in
      males than in females. Statistically significant differences by gender were
      observed for normals, diabetics without retinopathy, and diabetics with mild to
      moderate nonproliferative retinopathy (mean differences, 12, 14, and 18 microm,
      respectively; Ps = 0.0057, 0.0057, and 0.0002). For increasing retinopathy
      severity, the probability of macular thickening detected by OCT but not detected
      by clinical examination increased. Fifteen percent of eyes with severe
      nonproliferative or proliferative retinopathy and no clinically detected edema
      had OCT-measured macular thickening. CONCLUSIONS: Because OCT measurements are
      gender dependent, gender balance or statistical adjustment for gender imbalances
      of compared groups in OCT studies of diabetic macular edema is important. As
      retinopathy severity increases, the probability of subclinical edema rises.
      Except for an individual baseline measurement possibly useful for longitudinal
      comparison, the data suggest that there is little reason routinely to obtain OCT
      in eyes with diabetes and no retinopathy or mild to moderate diabetic retinopathy
      when clinical examination fails to show macular edema.

PMID- 18067961
TI  - Expression of AID transgene is regulated in activated B cells but not in resting
      B cells and kidney.
AB  - Activation-induced DNA cytidine deaminase (AID) is required for somatic
      hypermutation (SHM) and efficient class switch recombination (CSR) of
      immunoglobulin (Ig) genes. We created AID-transgenic mice that express AID
      ubiquitously under the control of a beta-actin promoter. When crossed with AID-/-
      mice, the AID-transgenic,AID-/- mice carried out SHM and CSR, showing that the
      AID transgenes were functional. However, the frequencies of SHM in V- and switch
      regions, and CSR were reduced compared to those in a wild type AID background.
      Several criteria suggested that the inefficiency of SHM was due to reduced AID
      activity, rather than lack of recruiting error-prone DNA repair. High levels of
      AID mRNA were produced in resting B cells and kidney, cells that do not express
      AID in wild type mice. Compared with these cells, activated B cells expressed
      about an order of magnitude less AID mRNA suggesting that there may be a post
      transcriptional mechanism that regulates AID mRNA levels in professional AID
      producers but not other cells. The AID protein expressed in resting B cells and
      kidney was phosphorylated at serine-38. Despite this modification, known to
      enhance AID activity, resting B cells did not undergo SHM. Apparently, the large
      amounts of AID in resting B cells are not targeted to Ig genes in vivo, in
      contrast to findings in vitro.

PMID- 18067963
TI  - Vitamin E and age-related cataract in a randomized trial of women.
AB  - OBJECTIVE: To investigate whether vitamin E supplementation decreases the risk of
      age-related cataract in women. DESIGN: Randomized, double-masked, placebo
      controlled trial. PARTICIPANTS: Thirty-nine thousand eight hundred seventy-six
      apparently healthy female health professionals aged 45 years or older.
      INTERVENTION: Participants were assigned randomly to receive either 600 IU
      natural-source vitamin E on alternate days or placebo and were followed up for
      presence of cataract for an average of 9.7 years. MAIN OUTCOME MEASURE: Age
      related cataract defined as an incident, age-related lens opacity, responsible
      for a reduction in best-corrected visual acuity to 20/30 or worse, based on self
      report and confirmed by medical record review. RESULTS: There was no significant
      difference between the vitamin E and placebo groups in the incidence of cataract
      (1159 vs. 1217 cases; relative risk [RR], 0.96; 95% confidence interval [CI],
      0.88-1.04). In subgroup analyses of subtypes, there were no significant effects
      of vitamin E on the incidence of nuclear (1056 vs. 1127 cases; RR, 0.94; 95% CI,
      0.87-1.02), cortical (426 vs. 461 cases; RR, 0.93; 95% CI, 0.81-1.06), or
      posterior subcapsular cataract (357 vs. 359 cases; RR, 1.00; 95% CI, 0.86-1.16).
      Results were similar for extraction of cataract and subtypes. There was no
      modification of the lack of effect of vitamin E on cataract by baseline
      categories of age, cigarette smoking, multivitamin use, or several other possible
      risk factors for cataract. CONCLUSIONS: These data from a large trial of
      apparently healthy female health professionals with 9.7 years of treatment and
      follow-up indicate that 600 IU natural-source vitamin E taken every other day
      provides no benefit for age-related cataract or subtypes.

PMID- 18067964
TI  - Treatment of lower eyelid malposition with dermis fat grafting.
AB  - PURPOSE: To report a new technique in the repair of lower eyelid malposition
      using dermis fat as a posterior lamellar spacer graft. DESIGN: Retrospective,
      consecutive, nonrandomized interventional case series. PARTICIPANTS: Eleven
      patients who underwent surgical correction for symptomatic lower eyelid
      malposition using dermis fat as a spacer graft. METHODS: Patients with
      symptomatic lower eyelid malposition after blepharoplasty, trauma, craniofacial
      syndromes, and human immunodeficiency virus-associated lipodystrophy were treated
      with midfacial lifting combined with dermis fat posterior lamellar spacer
      grafting. MAIN OUTCOME MEASURES: Preoperative and postoperative measurements of
      eyelid position, margin-to-reflex distance (defined as the distance from the
      upper eyelid to the central corneal light reflex and the distance from the lower
      eyelid to the corneal light reflex), lagophthalmos, corneal staining, presence of
      ocular surface symptoms, and patient satisfaction. RESULTS: All patients who
      underwent dermis fat spacer grafting during lower eyelid malposition repair noted
      improvement in ocular surface symptoms and restoration of normal eyelid position.
      CONCLUSIONS: Dermis fat is a novel posterior lamellar spacer graft and offers
      numerous advantages over conventional lower eyelid spacer grafts for repair of
      lower eyelid malposition.

PMID- 18067965
TI  - Long-term survival of central visual field in end-stage glaucoma.
AB  - PURPOSE: To evaluate the long-term survival of visual field and visual acuity in
      treated glaucoma patients with end-stage glaucomatous visual field loss defined
      by a field constricted to a 10-degree radius or less. DESIGN: Retrospective chart
      review. PARTICIPANTS: Sixty-four patients with end-stage glaucoma. METHODS:
      Serial 10-2 Humphrey visual fields with size III stimulus were analyzed. The
      following data were recorded for each visual field: mean deviation (MD), pattern
      standard deviation, the largest horizontal and vertical diameters measured in
      degrees including only locations with thresholds of 10 decibels or more, and the
      number of points on the pattern deviation plot with a probability value of more
      than 5%. MAIN OUTCOME MEASURE: Change in visual acuity and visual field. RESULTS:
      Eighty-four eyes of 64 patients satisfied inclusion criteria with an average
      follow-up of 8.34+/-3.1 years. Seventy-eight percent of patients were black.
      During the study period, 14 eyes lost more than 3 lines of visual acuity. Of
      these 14, 8 eyes progressed to a visual acuity of 20/200 or worse. Seven eyes
      lost 3 decibels or more from the MD that could be reproduced over 2 visual
      fields. CONCLUSIONS: In this predominantly black population, most treated
      patients with end-stage glaucoma did not demonstrate a decline in visual acuity
      or progressive loss of the central visual field during long-term follow-up.

PMID- 18067966
TI  - Clinical spectrum of choroidal nevi based on age at presentation in 3422
      consecutive eyes.
AB  - PURPOSE: To evaluate the clinical features of choroidal nevi based on patient age
      at presentation and to investigate features of the nevi that are predictive of
      patient symptoms. DESIGN: Observational case series. PARTICIPANTS: Three thousand
      four hundred twenty-two consecutive eyes of 3187 patients. METHODS: Retrospective
      clinic-based study of clinical features at referral. Cox proportional hazards
      regressions were used for evaluation of factors predictive of patient symptoms.
      MAIN OUTCOME MEASURES: Nevus features as related to patient age group at
      diagnosis (young [< or =20 years], mid-adult [21-50 years], older adult [>50
      years]) and factors predictive of patient symptoms secondary to the nevus.
      RESULTS: Of the 3422 eyes with choroidal nevus, 63 (2%) were in young patients,
      795 (23%) in mid-adults, and 2564 (75%) in older adults. The following factors
      showed no substantial increase or decrease by age category (young, mid-adult,
      older adult) at presentation: symptoms (14%, 12%, 13%), mean nevus base (5.6,
      4.7, 5.2 mm), intrinsic nevus pigmentation (89%, 74%, 77%), related subretinal
      fluid (SRF) (11%, 15%, 9%), overlying orange pigment (6%, 10%, 6%), retinal
      pigment epithelial hyperplasia (0%, 9%, 7%), and retinal pigment epithelial
      atrophy (2%, 13%, 10%). The following factors statistically increased with age
      category: multiple nevi per eye (2%, 8%, 10%) (P = 0.0001), mean nevus thickness
      (1.2, 1.5, 1.6 mm) (P<0.0001), and overlying drusen (11%, 40%, 58%) (P<0.0001).
      Using multivariate analysis of the entire group, factors predictive of any
      symptom included nonpigmented nevus (P<0.001), location < or = 3 mm to foveola (P
      = 0.001), subfoveolar fluid (P = 0.002), any SRF (P = 0.02), and subfoveolar
      nevus (P = 0.027). CONCLUSIONS: Choroidal nevi show similar clinical features
      regardless of age of presentation, with the exception of increasing number of
      nevi per eye, slightly increasing thickness, and increasing drusen in adults
      versus younger patients. Symptomatic nevi are more likely to be nonpigmented,
      beneath the foveola, and with subfoveolar fluid.

PMID- 18067967
TI  - Arteriolar oxygen saturation, cerebral blood flow, and retinal vessel diameters.
      The Rotterdam Study.
AB  - OBJECTIVE: Retinal vessel diameters, in particular larger venular diameters, have
      been associated with cerebrovascular disease. Larger retinal venular diameters
      may reflect cerebral ischemia. The authors investigated whether arteriolar oxygen
      saturation (SaO2) and total cerebral blood flow (CBF), indicators of cerebral
      oxygen supply, are associated with retinal arteriolar or venular diameters.
      DESIGN: Cross-sectional study performed within the population-based Rotterdam
      Study. PARTICIPANTS: Randomly selected participants aged 55 years or older (n =
      696), who underwent both an eye examination and brain magnetic resonance imaging
      (MRI). METHODS: Arteriolar oxygen saturation was determined by pulse oximetry on
      the right index finger. Cerebral blood flow was assessed using a phase-contrast
      MRI sequence that measured the flow in the basilar and both internal carotid
      arteries. Brain volume was measured to express CBF per 100 ml brain volume.
      Retinal arteriolar and venular diameters were measured on digitized fundus color
      transparencies on 1 eye of each participant. Regression models were used to
      investigate the association of SaO(2) and CBF with retinal vessel diameters. MAIN
      OUTCOME MEASURES: Mean retinal arteriolar and venular diameters (in micrometers).
      RESULTS: Lower SaO2 was associated with larger venular diameters. Persons with
      SaO(2) less than 96% (n = 113) had on average 5 microm larger venular diameters
      compared with those with SaO(2) of 96% or more (n = 583; age- and gender-adjusted
      mean difference, 5.6 microm; 95% confidence interval, 1.2-10.0). Cerebral blood
      flow was not related to venular diameters when analyzed separately. Additional
      analyses showed that the association between SaO(2) and venular widening was
      confined to participants within the lowest tertile of CBF. No associations were
      found between SaO(2) or CBF and arteriolar diameters. Additional adjustment for
      established cardiovascular risk factors did not change the results. CONCLUSIONS:
      An association of lower SaO(2) with larger retinal venular diameters was
      observed, in particular in the presence of lower CBF. These findings suggest that
      venular widening may reflect a lower oxygen supply, especially to the brain.

PMID- 18067968
TI  - Vitrectomy for a symptomatic lamellar macular hole.
AB  - PURPOSE: To investigate the surgical findings and outcomes after vitrectomy for a
      lamellar macular hole (LMH). DESIGN: Retrospective, consecutive, interventional
      case series. PARTICIPANTS: Twenty-seven patients (27 eyes) with a lamellar
      macular hole and central vision loss. INTERVENTION: All patients underwent 3-port
      vitrectomy with internal limiting membrane (ILM) stripping by one of the authors.
      Best-corrected visual acuity (BCVA) and appearance by optical coherence
      tomography (OCT) were obtained preoperatively and postoperatively. MAIN OUTCOME
      MEASURES: Preoperative and postoperative BCVA and OCT imaging. RESULTS: Visual
      acuity improved postoperatively in 25 of 27 eyes (93%), with a mean improvement
      of 3.2 Snellen lines. Preoperative and postoperative OCT images were obtained in
      24 of 27 eyes (89%) and were judged to have improved or normalized in 22 of 24
      (92%) of these patients. CONCLUSION: In patients with central visual loss from a
      lamellar macular hole, vitrectomy with ILM stripping appears to be a beneficial
      treatment.

PMID- 18067969
TI  - Acute-onset endophthalmitis after clear corneal cataract surgery (1996-2005).
      Clinical features, causative organisms, and visual acuity outcomes.
AB  - PURPOSE: To report the clinical features, causative organisms, and visual acuity
      outcomes associated with endophthalmitis after clear corneal cataract surgery and
      to compare outcomes with those of the Endophthalmitis Vitrectomy Study (EVS).
      DESIGN: Retrospective consecutive case series. PARTICIPANTS: The study included
      73 eyes of 73 patients, mean age 76 years (range, 48-94 years), with
      endophthalmitis after clear corneal cataract surgery, including both referred and
      in-house patients. METHODS: The clinical and microbiology records were reviewed
      of all patients treated at a single medical center between January 1, 1996, and
      December 31, 2005, for clinically diagnosed, culture-positive endophthalmitis
      occurring within 6 weeks of clear corneal cataract surgery. MAIN OUTCOME
      MEASURES: Presence of hypopyon, mean time to endophthalmitis diagnosis, organisms
      cultured, and presenting and final visual acuities. RESULTS: The mean time
      between cataract surgery and diagnosis of endophthalmitis was 13 days (median, 9
      days; range, 1-39 days). Visual acuity at the time of diagnosis was <5/200 in 61
      of 73 (83.6%) patients, including light perception in 11 of 73 (15.1%). Hypopyon
      was present in 60 of 73 (82.2%) eyes. The initial treatment included intravitreal
      vancomycin, ceftazidime, and dexamethasone. A vitreous tap and intravitreal
      injection was performed in 54 of 73 (74.0%) eyes and pars plana vitrectomy in 19
      of 73 (26.0%) eyes. Coagulase-negative Staphylococcus was isolated in 50 of 73
      (68.4%) eyes. Other isolates included Staphylococcus aureus in 5/73 (6.8%) and
      Streptococcus species in 6 of 73 (8.2%). A visual acuity of > or =20/40 was
      achieved in 36 of 73 patients (49.3%) at final follow-up. CONCLUSIONS: The
      features and outcomes of endophthalmitis associated with clear corneal cataract
      surgery are similar to those reported in the EVS, which are associated with
      scleral incisions, but time to diagnosis was later with clear corneal incisions.

PMID- 18067970
TI  - Peripheral reticular pigmentary change is associated with complement factor H
      polymorphism (Y402H) in age-related macular degeneration.
AB  - OBJECTIVE: To examine phenotypes of age-related macular degeneration (AMD)
      patients with the complement factor H (CFH) variant (Y402H, C allele at
      rs1061170). DESIGN: Clinic-based case series study. PARTICIPANTS: The data set
      contained a total of 956 unrelated cases of AMD. METHODS: Age-related macular
      degeneration phenotypes of 796 carriers of the CFH Y402H variant were compared
      with the AMD phenotypes of 160 noncarriers. MAIN OUTCOME MEASURES: Presence or
      absence of 34 phenotypic features. RESULTS: Of the 34 features analyzed, only
      peripheral reticular pigmentary change (PRPC) was associated with this CFH
      variant (P = 0.0006). The proportion of AMD cases with PRPC correlated with the
      number of CFH risk C alleles in a dose-response fashion. CONCLUSIONS: The CFH
      Y402H polymorphism is associated with PRPC, suggesting that AMD changes are not
      limited to the macula. Current AMD grading methods assess only the macula and
      should consider incorporating peripheral retinal changes. Phenotypes that suggest
      a high-risk genotype may prove valuable for diagnostic, therapeutic, and research
      purposes.

PMID- 18067971
TI  - Adaptation of the Behavioral Assessment and Research System (BARS) for evaluating
      neurobehavioral performance in Filipino children.
AB  - Neurobehavioral tests have long been used to assess health effects in exposed
      working adult populations. The heightened concern over the potential impact of
      environmental exposures on neurological functioning in children has led to the
      development of test batteries for use with children. There is a need for
      reliable, easy-to-administer batteries to assess neurotoxic exposure in children.
      One such test battery previously validated with Spanish- and English-speaking
      children ages 4 and older, combines computerized tests from the Behavioral
      Assessment and Research System (BARS) with non-computerized tests. The goal of
      the present study was to determine the feasibility of using standardized
      neurobehavioral tests in preschool and school-aged Filipino children. Test
      instructions were translated into the vernacular, Tagalog or Tagalog-English
      ("Taglish") and some instructions and materials were modified to be appropriate
      for the target populations. The battery was administered to 4-6-year-old Filipino
      children (N=50). The performance of the Filipino children was compared to data
      previously collected from Spanish- and English-speaking children tested in the
      US. The majority of children had no difficulty completing the tests in the
      battery with the exception of the Symbol-Digit test and Digit Span-reverse. The
      three groups showed similar patterns of performance on the tests and the older
      children performed better than the younger children on all of the tests. The
      findings from this study demonstrate the utility of using this test battery to
      assess cognitive and motor performance in Filipino children. Tests in the battery
      assess a range of functions and the measures are sensitive to age differences.
      The current battery has been utilized in several cultures and socio-economic
      status classes, with only minor modifications needed. This study demonstrates the
      importance of pilot testing the methods before use in a new population, to ensure
      that the test is valid for that culture.

PMID- 18067972
TI  - NeuReal: an interactive simulation system for implementing artificial dendrites
      and large hybrid networks.
AB  - The dynamic clamp is a technique which allows the introduction of artificial
      conductances into living cells. Up to now, this technique has been mainly used to
      add small numbers of 'virtual' ion channels to real cells or to construct small
      hybrid neuronal circuits. In this paper we describe a prototype computer system,
      NeuReal, that extends the dynamic clamp technique to include (i) the attachment
      of artificial dendritic structures consisting of multiple compartments and (ii)
      the construction of large hybrid networks comprising several hundred
      biophysically realistic modelled neurons. NeuReal is a fully interactive system
      that runs on Windows XP, is written in a combination of C++ and assembler, and
      uses the Microsoft DirectX application programming interface (API) to achieve
      high-performance graphics. By using the sampling hardware-based representation of
      membrane potential at all stages of computation and by employing simple look-up
      tables, NeuReal can simulate over 1000 independent Hodgkin and Huxley type
      conductances in real-time on a modern personal computer (PC). In addition, whilst
      not being a hard real-time system, NeuReal still offers reliable performance and
      tolerable jitter levels up to an update rate of 50kHz. A key feature of NeuReal
      is that rather than being a simple dedicated dynamic clamp, it operates as a fast
      simulation system within which neurons can be specified as either real or
      simulated. We demonstrate the power of NeuReal with several example experiments
      and argue that it provides an effective tool for examining various aspects of
      neuronal function.

PMID- 18067973
TI  - Efficacy of Interpersonal Psychotherapy plus pharmacotherapy in chronically
      depressed inpatients.
AB  - BACKGROUND: Clinical guidelines recommend the combination of pharmaco- and
      psychotherapy for the treatment of chronic depression, although there are only a
      few studies supporting an additive effect of psychotherapy. METHODS: Forty-five
      inpatients with a chronic Major Depressive Disorder were randomized to 5 weeks of
      either Interpersonal Psychotherapy (IPT) modified for an inpatient setting (15
      individual and 8 group sessions) plus pharmacotherapy or to medication plus
      Clinical Management (CM). The 17-item Hamilton Rating Scale for Depression was
      the primary outcome measure. The study included a prospective naturalistic follow
      up, 3- and 12-months after discharge. RESULTS: Intent-to-treat analyses revealed
      a significantly greater reduction of depressive symptoms as well as better global
      functioning of patients treated with IPT compared to the CM group at week 5.
      Response and sustained response rates differed significantly between the two
      treatment conditions, favouring the IPT group. Remission rates were considerably
      higher for IPT patients who completed the treatment (67% vs. 32%). Patients who
      initially responded to IPT exhibited greater treatment gains at 12 months since
      only 7% of these subjects relapsed compared with 25% of the CM subjects. In the
      long-term, additional IPT led to a lower symptom level and higher global
      functioning. LIMITATIONS: The study uses data of a subset of patients from a
      larger trial. Both treatment groups did not receive comparable amounts of
      therapeutic attention. Extrapolating the data from this inpatient study to
      chronically depressed outpatients may not be possible. CONCLUSIONS: Intensive
      combined treatment provides superior acute and long-term effects over standard
      treatment in chronically depressed inpatients.

PMID- 18067974
TI  - Antenatal risk factors for postnatal depression: a large prospective study.
AB  - BACKGROUND: This study measured antenatal risk factors for postnatal depression
      in the Australian population, both singly and in combination. Risk factor data
      were gathered antenatally and depressive symptoms measured via the beyondblue
      National Postnatal Depression Program, a large prospective cohort study into
      perinatal mental health, conducted in all six states of Australia, and in the
      Australian Capital Territory, between 2002 and 2005. METHODS: Pregnant women were
      screened for symptoms of postnatal depression at antenatal clinics in maternity
      services around Australia using the Edinburgh Postnatal Depression Scale (EPDS)
      and a psychosocial risk factor questionnaire that covered key demographic and
      psychosocial information. RESULTS: From a total of 40,333 participants, we
      collected antenatal EPDS data from 35,374 women and 3144 of these had a score >12
      (8.9%). Subsequently, efforts were made to follow-up 22,968 women with a
      postnatal EPDS. Of 12,361 women who completed postnatal EPDS forms, 925 (7.5%)
      had an EPDS score >12. Antenatal depression together with a prior history of
      depression and a low level of partner support were the strongest independent
      antenatal predictors of a postnatal EPDS score >12. LIMITATIONS: The two main
      limitations of the study were the use of the EPDS (a self-report screening tool)
      as the measure of depressive symptoms rather than a clinical diagnosis, and the
      rate of attrition between antenatal screening and the collection of postnatal
      follow-up data. CONCLUSIONS: Antenatal depressive symptoms appear to be as common
      as postnatal depressive symptoms. Previous depression, current
      depression/anxiety, and low partner support are found to be key antenatal risk
      factors for postnatal depression in this large prospective cohort, consistent
      with existing meta-analytic surveys. Current depression/anxiety (and to some
      extent social support) may be amenable to change and can therefore be targeted
      for intervention.

PMID- 18067975
TI  - Dimensional personality traits and treatment outcome in patients with major
      depressive disorder.
AB  - BACKGROUND: This study investigated the association between dimensional
      personality traits from the Five-Factor Model (FFM) and treatment outcome in
      patients with Major Depressive Disorder (MDD). METHODS: Six hundred forty-nine
      outpatients with MDD participated in a randomised double-blind longitudinal study
      for 6 months. Patients received a combination of medication and psychotherapy;
      they were randomised to medication condition (tianeptine or fluoxetine), and non
      randomly assigned to psychotherapy condition (supportive, cognitive-behavioural,
      or psychodynamic). The Montgomery Asberg Depression Rating Scale was used to
      assess depression severity. The Systeme de Description en Cinq Dimensions was
      used to assess the personality domains of the FFM. RESULTS: Group comparisons
      revealed that patients who responded to both medication and psychotherapy had
      lower Neuroticism (t=4.22, p<.01), and higher Extraversion (t=4.01, p<.01) and
      Openness to Experience scores (t=3.57, p<.01) compared to non-responders.
      Regression analyses, which controlled for shared variance among the five
      personality domains, indicated that Neuroticism (chi(2)=4.06, p=.04) and
      Conscientiousness (chi(2)=8.98, p<.01) were significantly and uniquely associated
      with response. The two-way interactions between NeuroticismxExtraversion
      (chi(2)=4.49, p=.03) and ExtraversionxConscientiousness (chi(2)=5.91, p=.01) were
      also associated with response. These results were mostly replicated across the
      treatment-completer and intent-to-treat samples. CONCLUSIONS: Dimensional
      personality traits predict response for individuals with MDD. LIMITATIONS: This
      study did not examine facet-level traits, patient pre-morbid personality and
      functioning, and additional patient characteristics. Results may not be
      generalizable to severely depressed or treatment refractory patients.

PMID- 18067976
TI  - The effects of obesity and fatty acids on the feline immune system.
AB  - Obesity is a rising problem in cats. It is a risk factor for several diseases and
      has been linked to impaired immunity. The goal of this study was to determine the
      effect of body composition and effects of diet on immune function in cats. Twenty
      eight short-term obese and 12 lean cats with equal gender distribution were
      evenly and randomly divided into two groups which were either fed a diet
      containing saturated (SFA) or long-chain n-3 polyunsaturated fatty acids (3-PUFA)
      for a period of 6 months prior to testing. Blood was collected by venipuncture
      from the jugular vein. Blood samples were analyzed in a double blind fashion. A
      complete blood count was performed and lymphocyte distribution was examined by
      flow cytometric analysis with specific fluorescein-conjugated subset markers.
      Immune function was measured as follows: the proliferative activity of different
      cellular fractions was tested with polyclonal mitogens such as lipopolysaccharide
      (LPS), phytohaemagglutinin (PHA), phorbol 12-myristate 13-acetate (PMA), Ca
      ionophore, and concanavalin A. Innate immune functions assessed were phagocytosis
      and natural killer cell (NK) cytotoxicity. A similar immune innate and adaptive
      immune response was elicited regardless of diet or body condition. However, there
      was no correlation between body condition, diet, and any of the quantitative and
      qualitative functional responses of the immune system. We conclude that short
      term obesity and the fatty acid composition of the diet do not alter immune
      responses in cats.

PMID- 18067977
TI  - Expression of c-Fos and CRF in the brains of rats differing in the strength of a
      fear response.
AB  - The aim of the study was to examine the neurochemical background of differences
      in the individual responses to conditioned aversive stimuli, using the strength
      of a rat conditioned freezing response (the contextual fear test), as a
      discriminating variable. It was shown that low responders (LR), i.e. rats with
      duration of a freezing response one standard error, or more, below the mean
      value, had a higher activity of the M2 cortical area, and the median raphe
      nucleus (c-Fox expression), in comparison to the high responders (HR), i.e. rats
      with the duration of a freezing response one standard error, or more, above the
      mean value. These animals had also stronger 5-HT- and CRF-related immunostaining
      in the M2 area, and increased concentration of GABA in the basolateral nucleus of
      amygdala (in vivo microdialysis). The LR group vocalized more during test session
      in the aversive band, and had higher serum levels of corticosterone, examined 10
      min after test session. It was shown that different natural patterns of
      responding to conditioned aversive stimuli are associated with different
      involvement of brain structures and with dissimilar neurochemical mechanisms.

PMID- 18067978
TI  - The major surface protease (MSP or GP63) in the intracellular amastigote stage of
      Leishmania chagasi.
AB  - The Leishmania spp. protozoa have an abundant surface metalloprotease called MSP
      (major surface protease), which in Leishmania chagasi is encoded by three
      distinct gene classes (MSPS, MSPL, MSPC). Although MSP has been characterized
      primarily in extracellular promastigotes, it also facilitates survival of
      intracellular amastigotes. Promastigotes express MSPS, MSPL, and two forms of
      MSPC RNAs, whereas amastigotes express only MSPL RNA and one MSPC transcript. We
      confirmed the presence of MSPC protein in both promastigotes and amastigotes by
      liquid chromatography-tandem mass spectrometry (LC-MS/MS). More than 10 MSP
      isoforms were visualized in both amastigotes and promastigotes using two
      dimensional immunoblots, but amastigote MSPs migrated at a more acidic pI.
      Promastigote MSPs were N-glycosylated, whereas most amastigote MSPs were not.
      Immuno-electron microscopy showed that two-thirds of the promastigote MSP is
      distributed along the cell surface. In contrast, most amastigote MSP localized at
      the flagellar pocket, the major site of leishmania endocytosis/exocytosis.
      Biochemical analyses indicated that most amastigote MSP is soluble in the
      cytosol, vesicles or organelles, whereas most promastigote MSP is membrane
      associated and GPI anchored. Activity gels and immunoblots confirmed the presence
      of a novel proteolytically active amastigote MSP of higher Mr than the
      promastigote MSPs. Furthermore, promastigote MSP is shed extracellularly whereas
      MSP is not shed from axenic amastigotes. We conclude that amastigotes and
      promastigotes both express multiple MSP isoforms, but these MSPs differ
      biochemically and localize differently in the two parasite stages. We hypothesize
      that MSP plays different roles in the extracellular versus intracellular forms of
      Leishmania spp.

PMID- 18067979
TI  - Filling the gap of intracellular dephosphorylation in the Plasmodium falciparum
      vitamin B1 biosynthesis.
AB  - Thiamine pyrophosphate (TPP), the active form of vitamin B1, is an essential
      cofactor for several enzymes. Humans depend exclusively on the uptake of vitamin
      B1, whereas bacteria, plants, fungi and the malaria parasite Plasmodium
      falciparum are able to synthesise thiamine monophosphate (TMP) de novo. TMP has
      to be dephosphorylated prior to pyrophosphorylation in order to obtain TPP. In P.
      falciparum the phosphatase capable to catalyse this reaction has been identified
      by analysis of the substrate specificity. The recombinant enzyme accepts beside
      vitamin B1 also nucleotides, phosphorylated sugars and the B6 vitamer pyridoxal
      5'-phosphate. Vitamin B1 biosynthesis is known to occur in the cytosol. The
      cytosolic localisation of this phosphatase was verified by transfection of a GFP
      chimera construct. Stage specific Northern blot analysis of the phosphatase
      clearly identified an expression profile throughout the entire erythrocytic life
      cycle of P. falciparum and thereby emphasises the importance of dephosphorylation
      reactions within the malaria parasite.

PMID- 18067980
TI  - RNA interference of Schistosoma mansoni cathepsin D, the apical enzyme of the
      hemoglobin proteolysis cascade.
AB  - The aspartic protease cathepsin D (Clan AA, Family A1) is expressed in the
      schistosome gut where it plays an apical role in the digestion of hemoglobin
      released from ingested erythrocytes. In this report, RNA interference approaches
      were employed to investigate the effects of knockdown of schistosome cathepsin D.
      Cultured schistosomules of Schistosoma mansoni were exposed by square wave
      electroporation to double stranded RNA (dsRNA) specific for cDNA encoding S.
      mansoni cathepsin D. RNAi-mediated reductions in transcript levels led to
      phenotypic changes including significant growth retardation in vitro and
      suppression of aspartic protease enzyme activity. In addition, black-pigmented
      heme, the end point by-product of normal hemoglobin proteolysis that accumulates
      in the schistosome gut, was not apparent within the guts of the treated
      schistosomules. Their guts appeared to be red in color, rather than black,
      apparently indicating the presence of intact rather than digested host
      hemoglobin. These phenotypic effects were apparent when either of two forms of
      dsRNA, a long form spanning the entire target transcript or a short form specific
      for the 3'-region was employed. Off-target effects were not apparent in
      transcript levels of the gut-localized cysteine protease cathepsin B1. Finally,
      cathepsin D may be an essential enzyme in the mammal-parasitic stages of
      schistosomes because schistosomules treated with dsRNA did not survive to
      maturity after transfer into Balb/c mice. These and earlier findings suggest
      that, given its essential function in parasite nutrition, schistosome cathepsin D
      could be developed as a target for novel anti-schistosomal interventions.

PMID- 18067981
TI  - Peak VO2 in elderly patients with heart failure.
AB  - The incidence and prevalence of heart failure increase with age. The cardinal
      manifestation of heart failure is exercise intolerance. The cardiopulmonary
      exercise test with determination of peak VO(2) provides an integrated measure of
      both central and peripheral abnormalities in heart failure. It is used to predict
      prognosis, identify patients for cardiac transplantation and to distinguish
      cardiac from pulmonary causes of unexplained dyspnea. Most data is derived from
      middle-aged patients with moderate to severe systolic heart failure. Many elderly
      patients suffer from diastolic heart failure and the value of cardiopulmonary
      exercise testing in diastolic heart failure and in the elderly has not been well
      studied. This review examines the physiology of aging and the clinical utility of
      exercise testing in elderly patients with heart failure.

PMID- 18067982
TI  - Pupil dilation in response preparation.
AB  - This study examined changes in pupil size during response preparation in a finger
      cuing task. Based on the Grouping Model of finger preparation [Adam, J.J.,
      Hommel, B. and Umilta, C., 2003b. Preparing for perception and action (I): the
      role of grouping in the response-cuing paradigm. Cognitive Psychology. 46, (3),
      302-358.; Adam, J.J., Hommel, B. and Umilta, C., 2005. Preparing for perception
      and action (II) Automatic and effortfull Processes in Response cuing. Visual
      Cognition. 12, (8), 1444-1473.], it was hypothesized that the selection and
      preparation of more difficult response sets would be accompanied by larger
      pupillary dilations. The results supported this prediction, thereby extending the
      validity of pupil size as a measure of cognitive load to the domain of response
      preparation.

PMID- 18067983
TI  - Analysis of daily and circadian gene expression in the rat pineal gland.
AB  - The mammalian pineal gland is an important component of the circadian system. In
      the present study, we examined the expression of roughly 8000 genes in the rat
      pineal gland as a function of time of day under light-dark (LD) cycles and in
      constant dark (DD) using oligo DNA microarray technique. We identified 47 and 13
      genes that showed higher levels at night and day, respectively, under LD. The
      same patterns of expression were also observed in DD. About half of the genes
      that peaked at night have a known biological function, i.e., transcription
      factors and proteins that are involved in signaling cascades, whereas 14 are
      expressed sequence tags and 8 have an unknown biological function. Twelve of the
      genes that were up-regulated at night were also up-regulated after 1h NE
      stimulation, thus suggesting that the expression of these genes is controlled by
      adrenergic mechanisms. Of the 13 genes that were up-regulated in the daytime, 6
      coded for proteins that are involved in intracellular signaling pathways. The
      results obtained with microarray analysis were well correlated with data obtained
      using real time quantitative RT-PCR. The present results provide new materials to
      dissect and understand the pineal physiology.

PMID- 18067984
TI  - The GPRLQPY motif located at the carboxy-terminal of the spike protein induces
      antibodies that neutralize Porcine epidemic diarrhea virus.
AB  - The spike protein of Porcine epidemic diarrhea virus is the main surface
      glycoprotein involved in virus attachment and entry and therefore is the target
      of neutralizing antibodies. Here, the immunogenicity of a novel antigenic domain
      found on the carboxy-terminal of the spike protein characterized by the peptide
      motif GPRLQPY, was evaluated. A synthetic peptide whose linear sequence is
      identical to the 24a.a. carboxy-terminal portion of the spike protein (S-CT24)
      elicited a strong antibody response in BALB/c mice that had specific reactivity
      against the S-CT24 and PEDV. These antibodies were shown to have a specific
      affinity to the GPRLQPY motif, as demonstrated by non-reactivity with a peptide
      that lacks this motif. In addition, antiS-CT24 antibodies exhibited neutralizing
      activities against KPEDV-9 in focus reduction neutralization tests suggesting
      that the GPRLQPY motif induces neutralizing antibodies against PEDV.

PMID- 18067985
TI  - Glycemic levels with glucose loading test during pregnancy and its association
      with maternal and perinatal outcomes.
AB  - OBJECTIVE: To evaluate the association between glycemic levels with glucose
      loading test during pregnancy and maternal and perinatal outcomes. METHODS:
      Retrospective analysis of 2059 singleton pregnancies screened for gestational
      diabetes mellitus at Gazi University Faculty of Medicine, Department of
      Obstetrics and Gynecology between January 2004 and December 2006 was conducted.
      Sensitivity and specificity of the 50 g glucose loading test was calculated for
      different cut-off values in our population. Maternal and perinatal outcomes in
      different groups with different results after screening test were compared.
      RESULTS: An increase in cut-off value from 140 to 145 mg/dl seems to be
      associated with a significant increase in specificity along with a tolerable
      decrease in sensitivity. A cut-off value of 147.5 mg/dl is associated with a
      higher specificity and a slightly lower sensitivity. However, the cut-off value
      150 mg/dl seems to be associated with a significant decrease in sensitivity. As
      for the upper limit, a cut-off value of 180 mg/dl is associated with a 90%
      specificity and a cut-off value of 200 mg/dl is associated with a 99%
      specificity. A 100% specificity could be reached only after a cut-off value of
      221 mg/dl. A GLT value of 180 mg/dl or higher was found to be associated with
      poor maternal and fetal outcomes, regardless of the result obtained after the
      diagnostic test. CONCLUSION: Results obtained after 50 g GLT should be evaluated
      separately for each patient and the diagnostic test which is time-consuming,
      uncomfortable and expensive can be omitted up to a cut-off value of 147.5 mg/dl,
      especially for those patients with no risk factors. Besides, a GLT value of 180
      mg/dl or higher proves the diagnostic test unnecessary as these patients are
      associated with unfavorable perinatal and fetal outcomes.

PMID- 18067986
TI  - Long-term use of a diabetes-specific oral nutritional supplement results in a low
      postprandial glucose response in diabetes patients.
AB  - BACKGROUND: To determine the effect of 12 weeks supplementation with a high-MUFA,
      high-fibre diabetes-specific oral nutritional supplement (ONS) on postprandial
      glucose response in type 2 diabetic patients at risk for malnutrition. METHODS:
      Forty patients participated in this randomised, controlled, double-blind,
      parallel-group study. Subjects consumed 2 x 200 ml of diabetes-specific ONS
      (Diasip) or standard ONS per day in addition to their normal diet. At baseline,
      after 6 and 12 weeks postprandial glucose responses and secondary parameters were
      assessed. RESULTS: Postprandial glucose responses (incremental area under curve)
      (p<0.01) and delta postprandial peak glucose concentration (p<0.01) were
      significantly lower in the diabetes-specific ONS group compared with the standard
      ONS group at all visits. In time, iAUC glucose (p=0.074, t=0 week vs. t=12 weeks)
      and delta postprandial peak plasma glucose concentration (p<0.05, t=0 week vs.
      t=12 weeks) were decreased within the diabetes-specific ONS group, but not in the
      standard ONS group. No significant differences in fasting glucose, insulin,
      HbA1c, lipid profile, hs-CRP, oxidized LDL and malondialdehyde, laboratory safety
      parameters and nutritional status parameters were found between both groups at
      either of the visits. CONCLUSIONS: These data demonstrate that diabetic patients
      at risk for malnutrition benefit from use of this diabetes-specific ONS to
      improve postprandial blood glucose control.

PMID- 18067987
TI  - Erythromelalgia in a diabetic patient managed with gabapentin.

PMID- 18067988
TI  - Association between patient age and hospitalization resource use in a teaching
      hospital in Japan.
AB  - OBJECTIVES: This study examined the association between patient age and
      cumulative resource use during a 1-year period among patients in a Japanese
      hospital, as well as the equality of resource distribution between age groups.
      METHODS: We analyzed the administrative data for 9695 patients 35 years or older
      at a tertiary hospital. Multiple linear regression models were used to identify
      factors associated with cumulative resource use, including total charges,
      diagnostic examination charges, and drug charges, during a 1-year period. Gini
      coefficients were estimated to examine equality of cumulative resource use
      between age groups. RESULTS: Multiple linear regression analyses revealed a
      quadratic relationship between age and cumulative charges for all fees,
      diagnostic examinations, and drugs among surviving patients. However, age did not
      significantly associate with cumulative resource use among non-surviving
      patients. On the other hand, the cumulative duration of hospitalization (natural
      log-transformed) was strongly associated with resource use among all patients,
      both surviving and non-surviving. Cumulative resource use for inpatients was
      substantially unequal, but these inequalities of resource use did not correspond
      to age divisions. CONCLUSIONS: No linear association was found between patient
      age and cumulative resource use during a 1-year period among either surviving or
      non-surviving patients on multivariate regression analyses and the inequality of
      resource use among non-surviving patients differed by age group.

PMID- 18067989
TI  - Toss me a cigarette, I think there's one in my raincoat.

PMID- 18067990
TI  - Neuroinflammation: implications for the pathogenesis and molecular diagnosis of
      Alzheimer's disease.
AB  - During the past few years, an increasing set of evidence has supported the major
      role of deregulation of the interaction patterns between glial cells and neurons
      in the pathway toward neuronal degeneration. Neurons and glial cells, together
      with brain vessels, constitute an integrated system for brain function.
      Inflammation is a process related with the onset of several neurodegenerative
      disorders, including Alzheimer's disease (AD). Several hypotheses have been
      postulated to explain the pathogenesis of AD, but none provides insight into the
      early events that trigger metabolic and cellular alterations in neuronal
      degeneration. The amyloid hypothesis was sustained on the basis that Abeta
      peptide deposition into senile plaques is responsible for neurodegeneration.
      However, recent findings point to Abeta oligomers as responsible for synaptic
      impairment in neuronal degeneration. Amyloid is only one among many other major
      factors affecting the quality of neuronal cells. Another explanation derives from
      the tau hypothesis, supported by the observations that tau hyperphosphorylations
      constitute a common feature of most of the altered signaling pathways in
      degenerating neurons. Altered tau patterns have been detected in the
      cerebrospinal fluids of AD patients, and a close correlation was observed between
      the levels of hyperphosphorylated tau isoforms and the degree of cognitive
      impairment. On the other hand, the anomalous effects of cytokines and trophic
      factors share in common the activation of tau hyperphosphorylation patterns. In
      this context, a neuroimmunological approach to AD becomes relevant. When glial
      cells that normally provide neurotrophic factors essential for neurogenesis are
      activated by a set of stressing events, they overproduce cytokines and NGF, thus
      triggering altered signaling patterns in the etiopathogenesis of AD. A solid set
      of discoveries has strengthened the idea that altered patterns in the glia-neuron
      interactions constitute early molecular events within the cascade of cellular
      signals that lead to neurodegeneration in AD. A direct correlation has been
      established between the Abeta-induced neurodegeneration and cytokine production
      and its subsequent release. In effect, neuroinflammation is responsible for an
      abnormal secretion of proinflammatory cytokines that trigger signaling pathways
      that activate brain tau hyperphosphorylation in residues that are not modified
      under normal physiological conditions. Other cytokines such as IL-3 and TNF-alpha
      seem to display neuroprotective activities. Elucidation of the events that
      control the transitions from neuroprotection to neurodegeneration should be a
      critical point toward elucidation of AD pathogenesis.

PMID- 18067991
TI  - Ozone therapy: clinical and basic evidence of its therapeutic potential.
AB  - Ozone has recently been subjected to criticism and emphasis in relation to
      clinical efficacy and toxicity, respectively. Without a doubt, ozone, in common
      with oxygen itself, is one of the most potent oxidants. Ozone is considered one
      of the major pollutants in urban areas. Nevertheless, increasingly widespread use
      lately has highlighted the potential benefits as a therapeutic agent when used
      according to well-defined and safe protocols. Basic studies conducted following
      rigorous scientific and ethical criteria have been proposed for scientific
      discussion. This paper concerns original data on an in vivo model of Parkinson's
      disease and published data on the effect of low ozone doses with any risk of
      toxicity excluded with the concentrations commonly used in medical applications.

PMID- 18067992
TI  - Higher physiological doses of nandrolone decanoate do not influence the Bezold
      Jarish reflex control of bradycardia.
AB  - BACKGROUND: We investigated the influence of short-term treatment with
      supraphysiological doses of an anabolic-androgenic steroid on the Bezold-Jarisch
      reflex (BJR) control of heart rate (HR) and whether this treatment induced
      cardiac hypertrophy and anabolic effects in rats. METHODS: Male rats were treated
      with nandrolone decanoate (10 mg/kg(-1) body weight/4 weeks; DECA) or vehicle
      control (CON). After 4 weeks of treatment, BJR was evaluated by bradycardia
      responses that were elicited by serotonin administration (2-32 microg/kg(-1)).
      Mean arterial pressure (MAP) was assessed and cardiac hypertrophy was determined
      by the left ventricle weight/body weight (LVW/BW) ratio. Histological analyses of
      LV and the measurement of the total body protein content of the animals were
      performed. RESULTS: Nandrolone decanoate (ND) treatment had no effect on the MAP
      (CON=105+/-5; DECA=110+/-3 mmHg). However, the mean basal HR of DECA animals was
      significantly lower than that of control animals (CON = 381+/-14; DECA=324+/-12
      bpm; p<0.01). ND did not change the sensitivity of the BJR. The LVW/BW ratio
      indicated significant hypertrophy of the LV in DECA animals (CON=1.76+/-0.04;
      DECA=2.0+/-0.04 mg/g; p<0.01). Histological and morphometrical analyses
      demonstrate that there is also modest myocyte hypertrophy (CON=14.5+/-1.5;
      DECA=20.0 +/- 0.9 myocyte nuclei/field; p<0.05). However, the Masson-trichromic
      stained samples showed an enhancement of collagen deposits on the LV matrix.
      CONCLUSIONS: We concluded that 4 weeks ND treatment induced an anabolic effect
      and the beginnings of LV remodeling, mainly due to excessive collagen deposition
      in the cardiac extracellular matrix. However, the treatment did not influence BJR
      control of bradycardia, an effect that could be explained by an enhanced efferent
      vagal tonus in DECA animals.

PMID- 18067993
TI  - Mycobacterium bovis BCG Toll-like receptors 2 and 4 cooperation increases the
      innate epithelial immune response.
AB  - BACKGROUND: Although CXCL8 is known to be important both in enhancing local
      antimycobacterial activity and in driving recruitment of leukocyte subsets during
      inflammatory processes, little information is known about the relationship
      between transcriptional upregulation of the Mycobacterium bovis BCG-induced CXCL8
      secretion and TLR signaling. METHODS: Phosphorylation of ERK1/2 was analyzed by
      immunoblot analysis. The levels of immunoreactive CXCL8 were measured with
      cytokine-specific commercial ELISA kits. By using antibodies against both TLR2
      and TLR4, the levels of CXCL8 mRNA were determined by RT-PCR. RESULTS: In this
      study, we found that the inhibition of TLR2 significantly, and that of TLR4
      partially, decreased the ERK1/2 activation and the subsequent CXCL8 secretion
      induced by the M. bovis BCG when neutralizing antibodies to TLR2 or TLR4 were
      applied to human epithelial cells. Moreover, it is important to note that the
      levels of CXCL8 secretion and mRNA were markedly (94%) reduced by functional
      blocking of both TLR2 and TLR4. Under the same conditions, control stimulation
      with TLR4 (LPS) was markedly blocked with an anti-TLR4 antibody. Finally, when
      ERK1/2 activity was inhibited in TLR2- or TLR4-expressing cells, M. bovis BCG
      dependent CXCL8 production resulted in a significant inhibition. CONCLUSIONS:
      Together these results suggest that the M. bovis BCG, acting through both TLR2
      and TLR4, induces the activation of the ERK1/2 MAPK pathway, which in turn plays
      a major role in CXCL8 secretion.

PMID- 18067994
TI  - Mobile phone exposure does not induce apoptosis on spermatogenesis in rats.
AB  - BACKGROUND: Some studies have reported that microwave radiation can have adverse
      effects on reproduction. Therefore, the purpose of this study was to investigate
      the apoptosis-inducing effect of mobile phone exposure on spermatogonia in
      seminiferous tubules. METHODS: The study was carried out on 31 Wistar albino
      adult male rats. The rats were separated into three groups in this study (cage
      control: 10, sham group: 7, and exposed group: 14). For the study group, rats
      were exposed to radiation 2 h/day (7 days/week) for 10 months. For the sham
      group, rats were placed into the carousel and the same procedure was applied
      except that the generator was turned off. For the cage control, nothing was
      applied to the rats in this group and they completed their life cycle in the cage
      during the study period. In this study, rats were sacrificed after 10 months of
      exposure and their testes were taken. Testes tissue was immunohistochemically
      stained for the active (cleaved) caspase-3. Positively stained cells were counted
      in up to ten different areas, and the frequency of positive cells was determined
      in percentage. Scoring was done by taking into account both the intensity of
      staining and the distribution of positively stained cells. Therefore, protein
      expression was evaluated by a semiquantitative scoring system. RESULTS: The final
      score for apoptosis of testes in the exposed group was not statistically
      significant according to the sham and the cage control groups (p>0.05).
      CONCLUSIONS: The results of this study showed that 2 h/day (7 days/week) exposure
      of 900 MHz radiation over a period of 10 months does not affect the active
      (cleaved) caspase-3 levels in testes, a well-known feature of typical apoptosis.

PMID- 18067995
TI  - Myelin-basic protein-reactive specific CD4+ and CD8+ NK lymphocytes induce
      morphological changes in neuronal cell bodies and myelin sheaths: implications
      for multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic disease characterized by loss of
      myelin. However, data indicate that autoimmune cells could directly impair
      neuronal cell bodies and myelin sheath is lacking. The aim of the present study
      was to determine morphological evidence of the direct impairment of neurons by
      autoreactive lymphocytes and to further identify the subtypes of these
      lymphocytes. METHODS: Lymphocytes activated by myelin basic protein (MBP) 83-99
      and neurons of human brain were co-cultured for 24 h. RESULTS: Observations
      through scanning electron microscope showed that MBP-specific lymphocytes (CD4+,
      CD8+ cells, and NK cells) aggregated in the vicinity of the neuronal cell bodies
      and the myelin sheaths and attacked them directly, resulting in the degeneration
      of both neurons. CONCLUSIONS: Our studies provide morphological evidences of the
      direct impairment of neuronal cell bodies and myelin sheaths by MBP-specific
      lymphocytes. Our studies also suggest that MBP-specific CD4+, CD8+, and NK cells
      might be involved in this process. These processes may play a role in the direct
      impairment of neurons and myelin sheaths in early stages of MS and provide
      evidences for the application of immunosuppressant therapy of MS.

PMID- 18067996
TI  - Chemical hypoxia-induced glucose transporter-4 translocation in neonatal rat
      cardiomyocytes.
AB  - BACKGROUND: AMP-activated protein kinase (AMPK) activation plays an essential
      role in glucose metabolism of the heart. This study aimed at investigating
      whether AMPK was involved in glucose transporter-4 (GLUT-4) translocation induced
      by azide-induced chemical hypoxia in primary cultured neonatal rat
      cardiomyocytes. METHODS: With or without adenine 9-beta-D-arabinofuranoside (ara
      A, AMPK inhibitor) preincubation, primary cultured rat cardiomyocytes were
      randomized to several groups as incubated with azide (the respiratory chain
      inhibitor), insulin, or 5-aminoimidazole-4-carboxyamide-1-beta-D-ribofuranoside
      (AICAR, an AMPK activator). Glucose uptake was measured through gamma
      scintillation and GLUT-4 protein was detected by Western blot for each group.
      RESULTS: Azide-induced chemical hypoxia and AICAR both increased glucose uptake
      and GLUT-4 translocation in cardiomyocytes, and AICAR had an additive effect on
      insulin action. Ara A decreased AICAR- and azide-induced glucose uptake and GLUT
      4 translocation but did not affect basal or insulin-stimulated glucose uptake.
      CONCLUSIONS: Azide-induced chemical hypoxia increased glucose uptake and GLUT-4
      translocation in neonatal rat cardiomyocytes through a mechanism that at least
      was partially mediated by AMPK activation.

PMID- 18067997
TI  - Improved immune function with donor B-cell infusion after semi-allogeneic bone
      marrow transplantation in mice.
AB  - BACKGROUND: Regeneration of the immune system after bone marrow transplantation
      (BMT) is a slow process, often prolonged by the development and treatment of
      graft vs. host disease (GVHD). Donor lymphocyte infusion using allogeneic T-cells
      is widely applied for the induction of GVHD, which is associated with the desired
      graft vs. leukemia effect. Due to the slow immune recovery, our objective was to
      accelerate the immune recovery post-BMT by B-cell injections. METHODS: T-cell
      depleted stem cells obtained from female C57BL/6 (B6) mice were transplanted into
      lethally irradiated (Balb/c x C57BL/6) F-1 female mice. Seven days post
      transplantation, murine B-cells of male C57BL/6 origin were infused into the T
      cell-depleted chimeras. Thirty and 60 days post-transplantation, PCR analysis of
      the Y-chromosome was carried out to detect male B-cells in the transplant
      recipients. In order to evaluate the specific antibody response, the donors were
      immunized by specific T-cell-dependent and -independent antigens. RESULTS: None
      of the T-cell-depleted transplanted mice developed GVHD during a follow-up period
      of 650 days, whereas all non-T-cell-depleted recipients died. At 60 days post
      transplantation, significantly higher levels of immunoglobulins (IgA, IgG1, IgG3
      isotypes) were seen in chimeras supplemented with male B-cells than in chimeras
      reconstituted with T-cell-depleted stem cells alone. CONCLUSIONS: Our data
      document the feasibility of administering B-cell therapy post-allogeneic BMT to
      improve recovery of the humeral arm of the immune system while avoiding GVHD.
      Furthermore, post-transplant B-cell administration may have an important impact
      as an alternative to IV immunoglobulin infusions.

PMID- 18067998
TI  - Staging, response to therapy, and restaging of lymphomas with 18F-FDG PET.
AB  - BACKGROUND: We undertook this study to determine the diagnostic accuracy of
      (18)FDG after three cycles and at the end of chemotherapy in non-Hodgkin's
      lymphoma (NHL) or Hodgkin's lymphoma (HL). We also evaluated the role of (67)Ga,
      bone marrow aspiration (BMA), and computed tomography (CT) in monitoring lymphoma
      treatment. METHODS: (18)FDG, (67)Ga, BMA, and CT were performed before
      chemotherapy on 40 untreated patients. (18)FDG and CT data were also obtained in
      28/40 patients after 3 cycles of chemotherapy and at the end of chemotherapy.
      Patients had a median follow-up of 18 months, 21 had NHL, 7 had HL. Age range was
      from 15 to 74 years. Histopathology considered the standard reference at the
      initial stage. Follow-up was a comparative study of all exam results. RESULTS:
      Initial staging for PET and CT was as follows: sensitivity (Se) was 100%,
      specificity (Sp) 100%, positive predictive value (PPV) 100%, negative predictive
      value (NPV) 0%, and accuracy (Ac) 100%. (67)Ga was Se, 64%; Sp, 0%, PPV, 100%;
      and Ac, 64%. After the third cycle of chemotherapy and at the end of
      chemotherapy, Se, Sp, PPV, NPV, and Ac were always higher with PET than with CT.
      Eighteen patients had complete response, and seven had partial or no response.
      CONCLUSIONS: (18)FDG had greater prognostic values than CT after the third and
      last cycle of chemotherapy. PET after three cycles of chemotherapy is predictive
      of 18-month outcome in patients with intermediate and aggressive NHL and HL and
      may help in the identification of patients who would benefit from more intensive
      treatment or from a change in chemotherapy.

PMID- 18067999
TI  - Muscle strength and power, maximum oxygen consumption, and body composition in
      middle-aged short-stature adults with childhood-onset growth hormone deficiency.
AB  - BACKGROUND: Growth hormone (GH) replacement in adult GH-deficient (GHD) patients
      is reported to have a long-term beneficial effect on muscle mass and function,
      these effects being greater in young males and in adult-onset compared with those
      with childhood-onset GHD. To date, more discordant data are reported on the
      degree of muscle impairment in untreated GHD patients, due to the large
      heterogeneity of this syndrome. METHODS: Muscle maximum total isotonic strength
      (ST), lower limb maximum power output (W), maximum aerobic capacity (VO(2)max)
      and body composition (by tetrapolar bio-impedentiometry) were evaluated in seven
      short-stature adults with childhood-onset GHD and in seven age-matched normal
      stature controls with comparable lifestyle and daily physical activity. RESULTS:
      Significant differences were found in body composition between control subjects
      and GHD patients, who presented higher adiposity (mean BMI+/-SD: GHD, 27.8+/-5.8
      kg/m(2); controls, 22.1+/-0.8 kg/m(2); p=0.047), larger fat mass (GHD, 21.8+/
      10.7 kg; controls, 8.8+/-3.5 kg; p=0.008), and lower fat-free mass (GHD, 65.8+/
      11.4 %; controls, 87.0+/-6.5 %; p=0.002). In absolute terms, GHD patients
      attained significantly lower values in ST (GHD, 2479+/-493 N; controls, 4578+/
      1476 N; p=0.008), W (GHD, 1092+/-452 W; controls, 1910+/-781 W; p=0.035) and
      VO(2)max (GHD, 1.68+/-0.40 l/min; controls, 2.67+/-0.84 l/min; p=0.035) than
      those attained by controls. The differences were still evident when the results
      were normalized by unit body mass, whereas they disappeared when the parameters
      were expressed per unit fat-free mass, suggesting for these patients the presence
      of an intrinsic muscle function in the same range as that of control subjects.
      CONCLUSIONS: Middle-aged and short-stature adults with childhood-onset GHD, who
      received discontinuous pit-GH substitution therapy only during childhood and have
      uncorrected long-lasting GHD, still retain a normal intrinsic muscle capability
      in attaining isotonic strength, generating anaerobic power as well as
      accomplishing oxidative processes. Nonetheless, it is not known which age
      dependent evolution in motor dysfunction could be expected in this subgroup of
      GHD patients, when ageing processes add up to hormonal deficiencies.

PMID- 18068000
TI  - No evidence of increased risk for certain highly atherogenic lipoprotein
      phenotypes in HIV-infected patients.
AB  - BACKGROUND: There is a need to assess whether human immunodeficiency virus (HIV)
      infected patients are more likely than noninfected individuals to have any of the
      specific lipoprotein combination profiles identified as the best predictors of
      future cardiovascular disease in the general population. METHODS: One hundred
      five infected patients, randomly selected from a Mexican HIV clinic, and 105 age-
      and gender-matched noninfected community volunteers, were enrolled to study the
      prevalence of each of three highly atherogenic lipoprotein phenotypes [high
      apolipoprotein (Apo)B/ApoA-I ratio, hypertriglyceridemia with high ApoB and
      hypoalphalipoproteinemia with high ApoB], and the relationship between time of
      exposure to antiretroviral therapy (ART) drug class and lipid changes. RESULTS:
      The highly atherogenic lipoprotein phenotypes were similarly frequent in both
      groups. There was a nonsignificant increased risk of dyslipidemia with longer
      exposure to any of the ART drug classes, although this hazard seems to be greater
      in patients with central fat accumulation. CONCLUSIONS: No evidence of increased
      risk for certain highly atherogenic lipoprotein phenotypes in HIV-infected
      patients was found. More than one pathogenic mechanism for ART-associated
      dyslipidemia is postulated.

PMID- 18068001
TI  - Expression of cyclooxygenase-2 and vascular endothelial growth factor-C
      correlates with lymphangiogenesis and lymphatic invasion in human gastric cancer.
AB  - BACKGROUND: Recent observations have suggested that overexpression of
      cyclooxygenase-2 (COX-2) promotes tumor lymphangiogenesis through an upregulation
      of vascular endothelial growth factor-C (VEGF-C) expression. It is unclear
      whether this mechanism also acts in gastric cancer. The aim of this study was to
      determine the relationship between COX-2 and VEGF-C expression in human gastric
      cancer, as well as to correlate with lymph node involvement, prognosis, and other
      clinicopathologic parameters. METHODS: Sixty-eight primary gastric cancers were
      immunohistochemically examined for COX-2, VEGF-C, vascular endothelial growth
      factor receptor-3 (VEGFR-3, also known as Flt-4), and CD34 expressions.
      Assessment of Flt-4-positive vessel density (FVD) and microvessel density (MVD)
      was performed. Then we analyzed their relationships and correlations with
      clinicopathologic findings and patients' survival time. RESULTS: The positivity
      rate of COX-2 and VEGF-C in the primary tumor was 67.7 and 54.4 percent,
      respectively. A significant correlation was found between the expression of VEGF
      C and COX-2, and both were also correlated to MVD, FVD, lymphatic invasion, and
      TNM stage (p<0.05). COX-2 immunoreactivity was also associated with lymph node
      metastasis and serosa invasion. Increased MVD was significantly associated with
      lymph node metastasis and TNM stage. Both COX-2 and VEGF-C expression
      significantly correlated with poorer prognosis. CONCLUSIONS: Our data suggest
      that the expression of COX-2 correlates with VEGF-C expression and both of them
      correlate with the presence of lymphatic invasion and prognosis in gastric
      cancer. COX-2-mediated VEGF-C overexpression might promote lymphatic invasion via
      lymphangiogenesis pathway in patients with gastric cancer.

PMID- 18068002
TI  - Biokinetics and dosimetry of 188Re-anti-CD20 in patients with non-Hodgkin's
      lymphoma: preliminary experience.
AB  - BACKGROUND: Radioimmunotherapy is a molecular targeting treatment for high-risk
      leukemia and lymphoma. Rhenium-188-labeled anti-CD66 monoclonal antibody has been
      used successfully in patients with high-risk acute myeloid leukemia or
      myelodysplastic syndrome. Our aim was to establish the biokinetics of (188)Re
      anti-CD20 in patients and to evaluate its dosimetry as a target-specific
      radiopharmaceutical for non-Hodgkin's lymphoma (NHL) radioimmunotherapy. METHODS:
      Whole-body images were acquired at various times after administration of (188)Re
      anti-CD20, obtained from instant freeze-dried kit formulations with radiochemical
      purity >95%. Regions of interest (ROIs) were drawn around source organs in each
      time frame. The cpm of each ROI was converted to activity using the conjugate
      view counting method. The image sequence was used to extrapolate time-activity
      curves in each organ to calculate the total number of disintegrations (N) that
      occurred in the source regions. N data were the input for the OLINDA/EXM code to
      calculate internal radiation dose estimates. RESULTS: Dosimetric studies
      indicated that after administration of 4.87-8.72 GBq of (188)Re-anti-CD20, the
      absorbed dose to total body would be 0.75 Gy, which corresponds with the
      recommended dose for NHL therapies. CONCLUSIONS: The calculated absorbed doses of
      (188)Re-anti-CD20 indicate that it may be used in radioimmunotherapy. Therefore,
      these preliminary data justify a full assessment of the safety, toxicity, and
      efficacy of (188)Re-anti-CD20 in a clinical study.

PMID- 18068003
TI  - Influence of insulin resistance and adipocytokines on elevated serum alanine
      aminotransferase in obese patients.
AB  - BACKGROUND: Insulin resistance and adipocytokines have been associated with fatty
      liver and nonalcoholic fatty liver disease. The aim of our study was to study the
      influence of insulin resistance and adipocytokines in obese patients on elevated
      serum alanine aminotransferase (ALT). METHODS: A population of 214 female obese
      patients was studied cross-sectionally. HOMA-IR was calculated as indicator of
      insulin resistance. Adipocytokines (leptin, resistin, adiponectin, interleukin-6,
      and TNF-alpha) blood levels were measured. RESULTS: The mean age and body mass
      index of our study group was 38.2+/-14.7 years and 35.27+/-6.5, respectively.
      HOMA and leptin levels were higher in the third ALT tertile than in the first ALT
      tertile. Adiponectin level was higher in the first tertile than in the second and
      third tertiles. These parameters show statistical differences between the second
      and third ALT tertiles. In the multiple regresion analysis with a dependent
      variable (ALT) and the statistical univariant variables as independent variables,
      the HOMA-IR remained in the model with an increase of 0.27 U/L of ALT (CI 95%,
      0.6-3.4) (F=8.1; p<0.05) with each 1 unit of HOMA-IR adjusted by age, weight, and
      dietary intake. CONCLUSIONS: Some metabolic parameters are associated with
      elevated ALT in obese female patients. However, adjusted by other variables, only
      insulin resistance remained associated.

PMID- 18068004
TI  - Mycophenolate mofetil in low doses stabilizes and improves antineutrophil
      cytoplasmic antibody-associated vasculitis and lupus nephritis.
AB  - BACKGROUND: Clinical experience with mycophenolate mofetil (MMF) in
      glomerulonephritis still remains limited. METHODS: In order to assess the
      experience of one center with the efficacy and tolerability of MMF in patients
      with glomerulonephritis, we performed a retrospective 6-year analysis of 68
      patients treated by MMF for glomerular disease, mainly anti-neutrophil
      cytoplasmic antibody-associated vasculitis (AAV: n=34) and systemic lupus
      erythematosus and lupus nephritis (SLE: n=24). Indications were maintenance
      treatment in 40% of patients, induction treatment in patients not tolerating
      cyclophosphamide in 27%, and disease relapse in 33%. Mean treatment duration was
      11.5 months. RESULTS: Efficacy endpoints were serum creatinine, urinary protein
      excretion, and steroid dose. In AAV patients, MMF was associated with significant
      improvement in 18%, partial improvement in 26%, stabilization in 29%, and disease
      progression in 12%; adverse event dropouts totalled 15%. In SLE, the respective
      figures were 30, 22, 9, and 22%, with 17% adverse event dropouts. The most
      frequent side effects were gastrointestinal events (n=7) and infections (n=3).
      None was life-threatening and there were no deaths. CONCLUSIONS: MMF, in the
      relatively low doses used, was safe and effective, stabilizing or improving AAV
      in 73% of patients and SLE in 61%. Further prospective randomized controlled
      trials with MMF in renal vasculitis and lupus nephritis are clearly warranted.

PMID- 18068005
TI  - Management of infected femoral pseudoaneurysms in intravenous drug abusers: a
      review of 57 cases.
AB  - BACKGROUND: The present study was carried out to evaluate the clinical
      characteristics and surgical methods used for the management of infected femoral
      pseudoaneurysms secondary to illegal drug injections. METHODS: Fifty seven
      consecutive patients who presented with infected pseudoaneurysm of the lower limb
      and were admitted to the emergency department of Sina Hospital during a 5-year
      period were enrolled in this study. Surgical methods performed consisted of vein
      angioplasty, simple ligation of femoral artery, and emergent or delayed
      revascularization. RESULTS: All participating patients were males with a mean age
      of 36.7 years. Three (5.3%) and two (3.5%) patients underwent primary repair and
      emergent vascular bypass, respectively; whereas delayed revascularization was
      performed in only eight (14%) cases. Forty four (77.2%) patients achieved a
      normal lifestyle without any vascular bypass. Early critical ischemia and late
      claudication was reported in two (3.5%) and eight (14%) patients, respectively.
      Other complications such as amputation and mortality were rarely reported.
      CONCLUSIONS: In our study, simple ligation of the external iliac or femoral
      artery was the most frequent management method for treating infected femoral
      pseudoaneurysms. Simple ligation of the external iliac or femoral artery seems to
      be a safe procedure in drug abusers presenting with infected femoral
      pseudoaneurysms.

PMID- 18068006
TI  - The 677 C/T MTHFR polymorphism is associated with essential hypertension,
      coronary artery disease, and higher homocysteine levels.
AB  - BACKGROUND: Essential hypertension (EH) and cardiovascular disease are common,
      multifactorial disorders likely to be influenced by multiple genes of modest
      effect. The C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism
      is related to MTHFR enzyme activity and to plasma homocysteine (Hcy)
      concentration. This study was designed to investigate an association of this
      polymorphism with coronary artery disease (CAD), EH, and healthy subjects.
      METHODS: In this study, we measured serum folate, serum vitamin B12, and plasma
      homocysteine and determined the MTHFR C677T genotype of 78 patients with
      essential hypertension, 100 patients with coronary artery disease, and 100
      healthy subjects. MTHFR genotypes were assessed by real-time polymerase chain
      reaction. RESULTS: CC, CT, and TT genotype frequencies were 52, 44.0, and 4.0% in
      patients with CAD, respectively. In patients with essential hypertension, the CC,
      CT, and TT genotype frequencies were 46.2, 41.0, and 12.8%, respectively. In
      control subjects, the CC, CT, and TT genotype frequencies were 72.0, 26.0, and
      2.0%, respectively. The C allele was significantly more frequent in controls
      compared with patients with EH (p<0.05), and CC genotypes were more frequent in
      controls compared to patients with EH and CAD. Homocysteine level was higher in
      TT genotypes in CAD patients compared with CC and CT genotypes (p<0.01). MTHFR
      gene polymorphism is an independent risk factor for EH but not for CAD.
      CONCLUSIONS: The TT genotype of the 677C/T MTHFR polymorphism is associated with
      EH and CAD. In addition, TT genotypes had higher plasma Hcy levels in CAD
      patients compared with CC and CT genotypes. MTHFR gene polymorphism is an
      independent risk factor for EH but not for CAD.

PMID- 18068007
TI  - Analysis of CCG repeats in Huntingtin gene among HD patients and normal
      populations in Japan.
AB  - BACKGROUND: Huntington's disease (HD) is a hereditary autosomal dominant
      neurodegenerative disease characterized by motor, cognitive, and psychiatric
      symptoms. The molecular basis of the disease is the expansion of the
      trinucleotide CAG in the first exon of a gene on chromosome four (4p 16.3). There
      is another triplet sequence, a CCG repeat, immediately 3' adjacent to the CAG
      repeat in Huntingtin. This triplet sequence is also polymorphic, alleles of 7 or
      10 repeats are predominant in populations, and strong linkage disequilibrium
      between the CCG (7) allele and HD has been shown in western HD chromosomes,
      whereas Japanese HD chromosomes strongly associate with an allele of (CCG)10.
      METHODS: Distribution of CAG and the CCG repeats in Huntingtin in 15 patients
      with HD living in southern Japan were selected to evaluate the regional
      difference in the CCG repeat number in Japan. RESULTS: Among our 15 HD patients,
      only 4 patients had the (CCG)7 allele, and the (CCG)10 alleles were found in the
      remaining 11 patients. CONCLUSIONS: In this study, a linkage disequilibrium was
      found between Japanese HD chromosomes and (CCG)10, whereas western HD chromosomes
      are strongly associated with (CCG)7. These data suggest that (CCG)10 allele is
      dominant in southern Japan.

PMID- 18068008
TI  - Seven and 3.5-day rhythms in the incidence of myocardiopathies in Mexico.
AB  - BACKGROUND: There is recent evidence about the existence of 7- and 3.5-day
      rhythms in some biological systems, particularly in human diseases. The objective
      of this work was to analyze and compare health data from various sources in
      Mexico to find this rhythm and a plausible explanation. METHODS: We analyzed the
      hourly number of myocardial infarctions (MI), angina, arrhythmias, hypertension,
      and heart failure registered at the Clinical Research Department of Hospital de
      Cardiologia of Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro
      Social, in Mexico City for a period of 1 year (1996), with a total of 4947 cases.
      We used two methods based on the Fast Fourier Transform algorithm to determine
      the periodicities of this data. RESULTS: A predominant 1-day rhythm was found in
      the hourly data, and important periodicities of approximately 7- and 3.5-day
      among other rhythms. These periodicities were also found in other medical data
      from different sources in Mexico, particularly a long database of MI mortality
      for the whole country. CONCLUSIONS: The explanation of the 7-day rhythm may be
      related to the social week of human activity, but the 3.5-day rhythm has no easy
      explanation. Here we discuss the possibility that these rhythms may be related to
      environmental conditions, particularly to the solar activity that has periods
      close to the 3.5 and 7 days. Regardless of the modest number of data, the finding
      of these rhythms on the incidence of MI and other cardiac-related diseases in
      Mexico confirms previous investigations concerning medical data from other
      Mexican health care institutions.

PMID- 18068009
TI  - The bone marrow as a potential receptor site for pancreatic islet grafts.
AB  - BACKGROUND: Pancreatic islet transplantation in the human liver is being
      performed with increasing success to treat diabetes. However, the liver as a
      receptor site has many drawbacks due to immunological and non-immunological
      factors as well as important technical limitations. Bone marrow offers an easily
      accessible extrahepatic receptor site. Therefore, we attempted to explore the
      survival of pancreatic islets transplanted into the bone marrow of rats. METHODS:
      Pancreatic islets islografts and allografts were implanted into the bone marrow
      of rats. No immunosuppression was used. Morphology, presence of insulin, and
      glucagon and signs of apoptosis and rejection were explored. RESULTS: Pancreatic
      islets can be successfully engrafted into the bone marrow of rats, maintaining a
      normal histological appearance in insulin and glucagon content and no signs of
      apoptosis or rejection. CONCLUSIONS: These preliminary findings suggest that the
      bone marrow is capable of maintaining pancreatic islets in the absence of
      immunosuppression and, thus, can constitute an immunoprivileged environment for
      engraftment.

PMID- 18068010
TI  - Relationship between A-3826G polymorphism in the promoter of the uncoupling
      protein-1 gene and high-density lipoprotein cholesterol in Japanese individuals:
      a cross-sectional study.
AB  - BACKGROUND: A-3826G polymorphism within the promoter region of the uncoupling
      protein-1 (UCP-1) gene is possibly involved in the pathophysiology of obesity and
      metabolic disorders. However, the effects of UCP-1 A-3826G polymorphism on high
      density lipoprotein cholesterol (HDL-C), a major contributor to atherosclerotic
      disease, still have not been established. METHODS: A total of 298 healthy
      Japanese subjects (144 males and 154 females, mean age: 45.2 years) with a body
      mass index (BMI) of 20.0-30.0 kg/m(2), regular lifestyles, and receiving no
      medication were enrolled in the cross-sectional study to estimate the
      relationship of serum HDL-C levels with UCP-1 A-3826G polymorphism by genomic PCR
      and Bcl1-restriction fragment length polymorphism analysis. We used 1.04 mmol/L
      of HDL-C in Japanese males and 1.29 mmol/L in Japanese females as cut-off values
      of low HDL-cholesterolemia. RESULTS: The genotype and allele frequencies of UCP-1
      A-3826G polymorphism were similar to those previously reported in the Japanese
      population. In males, HDL-C levels of the GG genotype (1.75+/-0.49 mmol/L) were
      significantly higher than those found in the AA genotype (1.45+/-0.34 mmol/L,
      p=0.015). In females, the occurrence rate of low HDL-cholesterolemia was
      significantly different by genotype: a low prevalence in the GG genotype (15.4%
      in the AA, 4.8% in the AG, 15.4% in the GG genotype, p=0.022). Logistic
      regression analysis was used to identify risk factors for low HDL
      cholesterolemia, with adjustments for age, gender, smoking, alcohol intake, BMI,
      hypertriglyceridemia, and genotype. The GG genotype was detected as being a
      significant associated factor (odds ratio =0.11 [95% confidence interval =0.01
      0.90], p=0.01), in addition to BMI and the presence of hypertriglyceridemia.
      CONCLUSIONS: These results suggest that the GG genotype may be an independent
      protective factor associated with low HDL-cholesterolemia in this population,
      although the role of the UCP-1 A-3826G polymorphism in HDL-C is complex and
      remains controversial. This hypothesis needs further investigation.

PMID- 18068011
TI  - Ambulatory transradial angioplasty in Mexico: is it possible?

PMID- 18068012
TI  - Shoe on the other foot.

PMID- 18068013
TI  - Stick stigma.

PMID- 18068014
TI  - Glucose basics.

PMID- 18068016
TI  - Soul mates.

PMID- 18068019
TI  - The dirty dozen.

PMID- 18068020
TI  - Footprints.

PMID- 18068021
TI  - Beyond the obvious.

PMID- 18068022
TI  - The more things change.

PMID- 18068024
TI  - San Diego firestorm 2007. Cooperative effort among agencies ensures seamless EMS
      response.

PMID- 18068025
TI  - The heart dangers of CO. Understanding cardiovascular risks to responders from CO
      exposure.

PMID- 18068026
TI  - Math phobic no more. Critical care calculations for the formula challenged.

PMID- 18068027
TI  - Professional boundaries. Where they are & why we cross them?

PMID- 18068028
TI  - The Russian way. A different structure of prehospital care & disaster response.

PMID- 18068029
TI  - Small town, big fire. Incident overview & lessons learned from EMS response &
      rehab operations in a rural community.

PMID- 18068030
TI  - First responder rehab. Good, better, best.

PMID- 18068032
TI  - HPV and cervical cancer in the 2007 report.

PMID- 18068035
TI  - Noninvasive risk assessment early after a myocardial infarction the REFINE study.
AB  - OBJECTIVES: This study sought to determine whether combined assessment of
      autonomic tone plus cardiac electrical substrate identifies most patients at risk
      of serious events after myocardial infarction (MI) and to compare assessment at 2
      to 4 weeks versus 10 to 14 weeks after MI. BACKGROUND: Methods to identify most
      patients at risk of serious events after MI are required. METHODS: Patients (n =
      322) with an ejection fraction (EF) <0.50 in the initial week after MI were
      followed up for a median of 47 months. Serial assessment of autonomic tone,
      including heart rate turbulence (HRT), electrical substrate, including T-wave
      alternans (TWA), and EF was performed, interpreted blinded, and categorized using
      pre-specified cut-points where available. The primary outcome was cardiac death
      or resuscitated cardiac arrest. All-cause mortality and fatal or nonfatal cardiac
      arrest were secondary outcomes. RESULTS: Mean EF significantly increased over the
      initial 8 weeks after MI. Testing 2 to 4 weeks after MI did not reliably identify
      patients at risk, whereas testing at 10 to 14 weeks did. The 20% of patients with
      impaired HRT, abnormal exercise TWA, and an EF <0.50 beyond 8 weeks post-MI had a
      5.2 (95% confidence interval [CI] 2.4 to 11.3, p < 0.001) higher adjusted risk of
      the primary outcome. This combination identified 52% of those at risk, with good
      positive (23%; 95% CI 17% to 26%) and negative (95%; 95% CI 93% to 97%) accuracy.
      Similar results were observed for the secondary outcomes. CONCLUSIONS: Impaired
      HRT, abnormal TWA, and an EF <0.50 beyond 8 weeks after MI reliably identify
      patients at risk of serious events. (Assessment of Noninvasive Methods to
      Identify Patients at Risk of Serious Arrhythmias After a Heart Attack;
      http://www.clinicaltrials.gov/ct/show/NCT00399503?order=1; NCT00399503).

PMID- 18068037
TI  - New methods for risk stratification in patients after myocardial infarction
      autonomic control and substrate sensitivity.

PMID- 18068036
TI  - Baroreflex sensitivity predicts long-term cardiovascular mortality after
      myocardial infarction even in patients with preserved left ventricular function.
AB  - OBJECTIVES: This study sought to assess the long-term predictive power of
      depressed baroreflex sensitivity (BRS) among post-myocardial infarction (MI)
      patients with preserved left ventricular function. BACKGROUND: Risk
      stratification after MI is primarily performed by identifying patients with
      depressed left ventricular ejection fraction (LVEF) because of their greater
      mortality. Autonomic markers can help refining risk stratification. Depressed BRS
      (<3 ms/mm Hg) correlated with cardiovascular mortality in 1,284 post-MI patients
      during a 21-month follow-up in the multicenter ATRAMI (Autonomic Tone and
      Reflexes After Myocardial Infarction) study, but had no significant predictive
      power in patients with LVEF >35% or above age 65 years. METHODS: Two hundred
      forty-four consecutive post-MI patients (age 59 +/- 10 years) with LVEF >35%
      (average 54 +/- 8%) were enrolled. They underwent a complete assessment,
      including BRS 4 weeks after MI. RESULTS: During a 5-year mean follow-up, 14
      (5.7%) patients died of cardiovascular causes. Multivariate analysis identified
      BRS (p = 0.0001), but not LVEF and age, as predictive of cardiovascular
      mortality. The relative risk (95% confidence interval [CI]) for depressed BRS was
      11.4 (95% CI 3.3 to 39.0) for the overall population, 19.6 (95% CI 4.1 to 94.8)
      for patients </=65 years, and 7.2 (95% CI 1.3 to 39.9) for patients above age 65.
      CONCLUSIONS: Even among the large number of low-risk post-MI patients with
      preserved left ventricular function, depressed BRS identifies, independently of
      age, a subgroup at long-term high risk for cardiovascular mortality in which more
      aggressive preventive strategies should be considered.

PMID- 18068038
TI  - Direct volumetric blood flow measurement in coronary arteries by thermodilution.
AB  - OBJECTIVES: This study sought to validate a new method for direct volumetric
      blood flow measurement in coronary arteries in animals and in conscious humans
      during cardiac catheterization. BACKGROUND: Direct volumetric measurement of
      blood flow in selective coronary arteries would be useful for studying the
      coronary circulation. METHODS: Based on the principle of thermodilution with
      continuous low-rate infusion of saline at room temperature, we designed an
      instrumental setup for direct flow measurement during cardiac catheterization. A
      2.8-F infusion catheter and a standard 0.014-inch sensor-tipped
      pressure/temperature guidewire were used to calculate absolute flow (Q(thermo))
      in a coronary artery from the infusion rate of saline, temperature of the saline
      at the tip of the infusion catheter, and distal blood temperature during
      infusion. The method was tested over a wide range of flow rates in 5 chronically
      instrumented dogs and in 35 patients referred for physiological assessment of a
      coronary stenosis or for percutaneous coronary intervention. RESULTS:
      Thermodilution-derived flow corresponded well with true flow (Q) in all dogs
      (Q(thermo) = 0.73 Q + 42 ml/min; R(2) = 0.72). Reproducibility was excellent
      (Q(thermo,)(1) = 0.96 x Q(thermo,)(2) + 3 ml/min; R(2) = 0.89). The measurements
      were independent of infusion rate and sensor position as predicted by theory. In
      the humans, a good agreement was found between increase of thermodilution-derived
      volumetric blood flow after percutaneous coronary intervention and increase of
      fractional flow reserve (R(2) = 0.84); reproducibility of the measurements was
      excellent (Q(thermo,)(1) = 1.0 Q(thermo,)(2) + 0.9 ml/min, R(2) = 0.97), and the
      measurements were independent of infusion rate and sensor position. CONCLUSIONS:
      Using a suitable infusion catheter and a 0.014-inch sensor-tipped guidewire for
      measurement of coronary pressure and temperature, volumetric blood flow can be
      directly measured in selective coronary arteries during cardiac catheterization.

PMID- 18068039
TI  - Broad and specific caspase inhibitor-induced acute repression of apoptosis in
      atherosclerotic lesions evaluated by radiolabeled annexin A5 imaging.
AB  - OBJECTIVES: The purpose of this study was to evaluate the role of caspase
      inhibitors on acute resolution of apoptosis in atherosclerotic lesions as
      evaluated by imaging with annexin A5. BACKGROUND: Extensive apoptosis of
      macrophages has been reported at the site of plaque rupture in patients dying of
      acute coronary syndrome. METHODS: Of 31 New Zealand White atherosclerotic
      rabbits, 6 received broad caspase, 3 received caspase-1, 3 received caspase-3, 3
      received caspase-8, and 4 received caspase-9 inhibitors; 12 animals did not
      receive any caspase inhibitors (treatment control group). Six unmanipulated
      rabbits were used for comparison (disease control group). Technetium-99m-labeled
      annexin A5 was used for imaging atherosclerotic lesions; 6 of the 12 uninhibited
      atherosclerotic rabbits received (99m)Tc-labeled mutant annexin A5 (radiotracer
      control group). Gamma images were obtained, and quantitative radiotracer uptake
      was compared with pathologic findings. RESULTS: Atherosclerotic lesions were best
      visible in untreated atherosclerotic rabbits. Quantitative annexin uptake,
      defined as the percent of injected dose per g of abdominal aorta tissue, was
      significantly higher in untreated atherosclerotic animals (mean +/- SD = 0.0515
      +/- 0.0099) compared with the normal rabbits (0.0065 +/- 0.0008; p < 0.0001) or
      atherosclerotic rabbits receiving mutant annexin (0.014 +/- 0.0024; p < 0.0001).
      Among all caspase inhibitor-treated rabbits, uptake was 39% lower (0.0314 +/-
      0.0151) than in untreated atherosclerotic animals (p < 0.01). Uptake was also
      significantly lower in rabbits receiving broad caspase (0.0206 +/- 0.0058; p <
      0.0001) or caspase-1, -3, or -9 (0.0272 +/- 0.0088, p < 0.01; 0.0286 +/- 0.0095,
      p < 0.01; 0.0300 +/- 0.0021, p < 0.01, respectively) inhibitors. Caspase-8
      inhibitor did not affect apoptosis (0.0618 +/- 0.0047; p = NS). Upon histologic
      characterization, a substantial decrease in macrophage apoptosis was observed in
      caspase-inhibited animals. CONCLUSIONS: Molecular imaging, using radiolabeled
      annexin A5, allows the detection of acute resolution of apoptosis as a result of
      caspase inhibition in experimental atherosclerosis. If proven clinically, this
      may allow development of novel intervention strategies in acute vascular events.

PMID- 18068040
TI  - Recombinant antibodies to an oxidized low-density lipoprotein epitope induce
      rapid regression of atherosclerosis in apobec-1(-/-)/low-density lipoprotein
      receptor(-/-) mice.
AB  - OBJECTIVES: The present study tested the hypothesis that treatment with human
      recombinant immunoglobulin G1 (IgG1) antibodies against a specific oxidized low
      density lipoprotein (oxLDL) epitope will induce regression of existing
      atherosclerotic lesions in LDL receptor-deficient mice expressing apolipoprotein
      B-100 (apoB-100) (Apobec-1(-/-)/LDLR(-/-)). BACKGROUND: Oxidized LDL plays an
      essential role in the pathogenesis of atherosclerosis. We previously showed that
      an antibody against oxLDL reduces progression of atherosclerosis in mice.
      METHODS: Apobec-1(-/-)/LDLR(-/-) mice were fed a high-fat diet until they were 24
      weeks and were subsequently transferred to chow. Starting at 25 weeks, mice were
      given 3 weekly injections of either of 2 recombinant human IgG1 antibodies (IEI
      E3 or 2D03) against a malondialdehyde-modified apoB-100 peptide sequence.
      RESULTS: At 25 weeks, atherosclerotic lesions covered 10.3 +/- 3.7% of the
      descending aorta. Transfer to chow diet resulted in a modest regression of
      atherosclerosis over a 5-week period (8.28 +/- 4.36%; p = NS). Antibody treatment
      induced additional regression of atherosclerosis by 50% (2D03; p = 0.001) and 36%
      (IEI-E3; p = 0.004) compared with control IgG1. The 2D03 treatment also reduced
      plaque inflammation, enhanced plaque expression of the adenosine triphosphate
      binding cassette transporter A1, and inhibited expression of monocyte
      chemoattractant protein-1 in cultured monocytes. CONCLUSIONS: Human IgG1 against
      a specific oxLDL epitope can induce rapid and substantial regression of
      atherosclerotic lesions, possibly by stimulating lipid efflux and inhibiting
      macrophage recruitment. These recombinant human antibodies could represent a
      novel strategy for rapid regression/stabilization of atherosclerotic lesions.

PMID- 18068041
TI  - Regression of atherosclerosis with therapeutic antibodies pipe cleaner or pipe
      dream?

PMID- 18068042
TI  - Global cardiovascular disease research survey.

PMID- 18068043
TI  - Highlights of the Second Annual Scientific Meeting of the Society of
      Cardiovascular Computed Tomography Washington, DC, July 6-8, 2007.

PMID- 18068044
TI  - Highlights of the 2007 scientific sessions of the American Society of Nuclear
      Cardiology San Diego, California, September 6-9, 2007.

PMID- 18068045
TI  - The year in heart failure.

PMID- 18068047
TI  - Recovery from postpartum cardiomyopathy in 2 patients by blocking prolactin
      release with bromocriptine.

PMID- 18068048
TI  - Exercise in chronic heart failure: does it need to be "anti-remodeling"?

PMID- 18068050
TI  - Two-level total en bloc lumbar spondylectomy with dural resection for metastatic
      renal cell carcinoma.
AB  - Only five reports of multilevel spondylectomy for tumor have been reported in the
      literature, mostly in the thoracic spine. We report a successful two-level
      spondylectomy with en bloc dural resection in a patient with metastatic renal
      carcinoma to the L3 and L4 vertebrae.

PMID- 18068051
TI  - Brain abscess caused by Nocardia nova.
AB  - Nocardia nova is a newly identified species of the Nocardia asteroides group and
      has recently been characterized as a human pathogen. To date, a few cases of N.
      nova pneumonia or subcutaneous abscess have been reported. We describe a patient
      with a brain abscess caused by N. nova in a patient receiving prednisolone and
      cyclophosphamide for nephrosis. Surgical excision and antibiotic treatment of the
      brain abscess were successful. This is the first detailed report of central
      nervous system infection due to N. nova.

PMID- 18068052
TI  - Coronary artery bypass surgery in the very old: light at the end of a tunnel or a
      dead-end road?

PMID- 18068053
TI  - Results and predictors of early and late outcomes of coronary artery bypass graft
      surgery in octogenarians.
AB  - OBJECTIVES: The aim of this study was to investigate early and late outcomes of
      coronary artery bypass graft (CABG) surgery in a large cohort of octogenarian
      patients. The results were compared with 2 other age groups including
      septuagenarians and patients <70 years old. DESIGN: A retrospective study of
      consecutive patients undergoing CABG surgery using a computerized database based
      on the New York State Department of Health registry. Data collection was
      performed prospectively. SETTING: A university hospital (single institution).
      PARTICIPANTS: Two thousand nine hundred eighty-five patients undergoing CABG
      surgery including 282 (9.4%) octogenarians, 852 (28.6%) septuagenarians, and 1851
      (62%) patients younger than 70 years old. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Patient characteristics, hospital mortality, morbidity, length of
      stay, and long-term survival were analyzed. Octogenarians were more likely female
      and presented significantly more often with comorbidities such as heart failure,
      an ejection fraction <30%, peripheral vascular disease, and aortic calcification.
      Crude hospital mortality was 4.6% (n = 13) in octogenarians compared with 2.2% (n
      = 19) in septuagenarians and 2.4% (n = 44) in patients <70 years old (p = 0.067).
      Respiratory failure and gastrointestinal complications occurred more frequently
      in octogenarians. The stroke rate was 1.6% and similar in the 3 age groups. In
      multivariate logistic regression analysis, age >80 years was not a predictor of
      hospital mortality. The length of stay was significantly higher in octogenarians
      compared with nonoctogenarians (16 +/- 24 days v 10 +/- 13 days, p < 0.001). Five
      year survival was 63% +/- 4% in octogenarians and was similar to that of an age-
      and sex-matched general US population. CONCLUSIONS: Excellent results after CABG
      surgery can be expected in octogenarians, with a minimal increase in
      postoperative mortality and acceptable postoperative morbidity. Respiratory
      failure is the main postoperative complication in octogenarians. Recent advances
      in operative techniques and perioperative management have contributed in
      improving surgical outcome in these patients compared with historic reports.

PMID- 18068054
TI  - Influence of intraoperative conversion from off-pump to on-pump coronary artery
      bypass grafting on costs and quality of life: a cost-effectiveness analysis.
AB  - OBJECTIVE: Off-pump coronary artery bypass (OPCAB) surgery has become a widely
      accepted alternative to standard coronary artery bypass graft (CABG) surgery
      using cardiopulmonary bypass; however, the influence of intraoperative conversion
      from OPCAB to standard CABG on costs and quality of life is unclear. The
      objective of this study was to determine whether intraoperative conversion
      affects costs and quality of life. DESIGN: A decision-analysis model and Monte
      Carlo simulation. SETTING: The US healthcare system over a maximum 10-year
      lifetime horizon. PARTICIPANTS: A hypothetical cohort of 60-year-old male
      patients undergoing elective OPCAB surgery or standard CABG surgery.
      INTERVENTIONS: Each patient was entered into the decision tree with varying
      transition probabilities. Outcome measures included quality-adjusted life-years
      (QALYs) and costs in US dollars. MEASUREMENTS AND MAIN RESULTS: In base-case
      analysis, OPCAB surgery led to a discounted lifetime cost of $91,282 and 7.64
      discounted QALYs, and standard CABG surgery led to $91,685 and 7.52 QALYs.
      Patients who required conversion from off-pump to on-pump surgery incurred a cost
      of $103,909 and gained 6.63 QALYs. OPCAB is dominant (less costly and more
      effective) if the conversion rate is below 8.5%, whereas costs increase
      exponentially if the probability of conversion exceeds 15%. Sixty-one percent of
      the Monte Carlo simulations favored cost-effectiveness of the OPCAB strategy.
      CONCLUSION: In low-risk patients, OPCAB surgery, in comparison to standard CABG
      surgery, would increase QALYs by reducing complications related to
      cardiopulmonary bypass, but it would result in lifetime costs similar to those of
      standard CABG surgery. The benefit of OPCAB may be offset by the risk of
      intraoperative conversion.

PMID- 18068055
TI  - The effect of routine intraoperative transesophageal echocardiography on surgical
      management.
AB  - OBJECTIVE: To assess the effects of routine intraoperative transesophageal
      echocardiography (TEE) on surgical management of patients undergoing all types of
      cardiac surgery. DESIGN: Prospective, observational. SETTING: A single
      institution, clinical investigation, university-affiliated hospital.
      PARTICIPANTS: Two hundred eighty-three consecutive patients undergoing cardiac
      surgery. INTERVENTIONS: A comprehensive TEE examination was performed in every
      patient after the induction of anesthesia. An appropriate surgical plan was then
      developed. A focused TEE examination was also performed at the conclusion of
      surgery. Whether or not TEE findings represented new information and whether or
      not this new information altered surgical management was documented. MEASUREMENTS
      AND MAIN RESULTS: There were 106 new TEE findings in 87 patients (31%). Half of
      the new findings involved the mitral valve, and a quarter involved the tricuspid
      valve. The new TEE information altered surgical management 77 ways in 71 patients
      (25%). Half of the altered surgical managements involved the mitral valve, and a
      third involved the tricuspid valve. In 8 patients (3%), TEE information
      influenced decisions regarding use/nonuse of cardiopulmonary bypass (CPB). In 2
      patients, TEE examination after the separation from CPB prompted reinitiation of
      CPB. In 1 patient, TEE examination after the induction of general anesthesia
      prompted cancellation of surgery. CONCLUSIONS: The routine use of TEE during
      cardiac surgery revealed new cardiac pathology in 1 of every 3 patients and led
      to altered surgical management in 1 of every 4 patients. TEE information also
      influenced decisions regarding use/nonuse of CPB in 3% of patients. Thus, the
      authors suggest that intraoperative TEE should be used routinely in all patients
      undergoing cardiac surgery.

PMID- 18068056
TI  - An intraoperative assessment of the ascending aorta: a comparison of digital
      palpation, transesophageal echocardiography, and epiaortic ultrasonography.
AB  - OBJECTIVES: There are a number of techniques available to assess the aorta for
      atheromatous disease in the intraoperative period. This study compared the
      relationship among the findings of digital palpation (DP), transesophageal
      echocardiography (TEE), and epiaortic ultrasound (EAU) in the detection of
      atheroma in the ascending aorta. DESIGN: A prospective, observational study.
      SETTING: A single-institution, cardiothoracic specialty hospital. PARTICIPANTS:
      One hundred fifty-four patients undergoing elective cardiac surgery.
      INTERVENTIONS: The ascending aorta of patients undergoing elective coronary
      artery bypass surgery was assessed for atheroma by means of the 3 techniques.
      Atheroma was scored as present or absent. The sensitivity and specificity of the
      techniques were compared. MEASUREMENTS AND MAIN RESULTS: Assuming EAU provides
      the "gold standard," the sensitivity of both TEE and DP were low. Digital
      palpation identified only 20 patients (12%); TEE 31 patients (20%); and, in
      contrast, EAU detected atheroma in 81 patients (53%). There were 3 and 6 false
      positives by DP and TEE, respectively. CONCLUSION: Assuming EAU as the "gold
      standard" to detect atheroma, this study has shown that when assessing the
      ascending aorta neither DP nor TEE appear sensitive. This study supports the
      proposal that detection of atheroma should be performed by EAU.

PMID- 18068057
TI  - High thoracic epidural anesthesia in coronary artery bypass surgery: a propensity
      matched study.
AB  - OBJECTIVES: To assess if 2 different anesthesia strategies, high-thoracic
      epidural anesthesia (HTEA) plus inhalation anesthesia and total intravenous
      anesthesia (TIVA) with sufentanil/propofol had different influence on outcomes of
      coronary artery bypass graft (CABG) surgery patients. DESIGN: Retrospective
      comparison of outcomes between HTEA and TIVA patients using propensity score pair
      wise matching of patients. SETTING: A university teaching hospital. PARTICIPANTS:
      A study of 1,473 consecutive patients undergoing elective CABG surgery; of these,
      476 (32%) received HTEA combined with inhalation anesthesia, whereas 997 (68%)
      underwent TIVA alone. INTERVENTIONS: The patients undergoing CABG surgery were
      offered the epidural-inhalation anesthetic approach. MEASUREMENTS AND MAIN
      RESULTS: Propensity matching yielded 389 pairs of patients. Patients were well
      matched in preoperative and operative features. Postoperative mortality,
      myocardial infarction, stroke, acute renal failure rates, and intensive care unit
      (ICU) stay were not statistically different in HTEA and TIVA groups. On the other
      hand, patients treated with HTEA had shorter ventilation times (5.8 +/- 3.11 v
      6.9 +/- 5.0 hours, HTEA and TIVA, respectively, p < 0.001); in addition,
      vasoconstrictors were more frequently used in cases of HTEA, whereas vasodilators
      were mainly used with TIVA both intra- and postoperatively. No neurologic
      complications related to the use of HTEA were observed. CONCLUSIONS: HTEA and
      TIVA provided similar early outcomes after CABG surgery, and there were no major
      differences between these 2 strategies in the average risk CABG patient
      populations. Although HTEA did not cause neurologic problems and yielded a
      significant reduction in time to extubation, a consistent benefit over standard
      techniques could not be shown.

PMID- 18068058
TI  - Effects of intrapleural analgesia on pulmonary function and postoperative pain in
      patients with chronic obstructive pulmonary disease undergoing coronary artery
      bypass graft surgery.
AB  - OBJECTIVE: Pain after coronary artery bypass graft (CABG) surgery remains a
      significant problem and may cause serious complications because of restricted
      breathing and limited early mobilization. The aim of this study was to assess the
      effects of intrapleural analgesia on the relief of postoperative pain in patients
      undergoing CABG surgery. DESIGN: Postoperative pain, pulmonary function tests,
      and outcomes were compared with a placebo group after CABG surgery in a double
      blind randomized clinical trial. SETTINGS: Cardiovascular surgery clinic.
      PARTICIPANTS: One hundred twenty-five patients with decreased lung function were
      studied. INTERVENTIONS: Group A (62 patients) received 20 mL of 0.5% bupivacaine
      bilaterally in the intrapleural spaces every 6 hours for 4 days, and group B (63
      placebo patients) received sterile saline solution. MEASUREMENTS AND MAIN
      RESULTS: Group A had a significantly shorter extubation time than the placebo
      group (8 +/- 1 h v 10 +/- 4 hours, p < 0.001). Blood gas analysis showed higher
      PaO2 and lower PaCO2 levels in group A. The patients receiving bupivicaine had
      significantly higher FEV1, FCV, VC, MVV, PEF, and FEF 25-75% values
      postoperatively when compared with the placebo group. Postoperative analgesic
      requirements and visual analog pain scales were significantly lower in group A.
      The intensive care unit stay in group A was shorter (1.2 +/- 0.7 v 1.4 +/- 0.6
      days, p = 0.04); however, the hospital stay did not differ between groups.
      CONCLUSIONS: Improvement in lung function parameters correlating with decreased
      postoperative pain with intrapleural bupivacaine was observed. Intrapleural
      analgesia provided a good level of analgesia, improved respiratory performance,
      and allowed rapid mobilization, which led to a reduction of postoperative
      respiratory complications.

PMID- 18068059
TI  - Postoperative analgesia with ketorolac is associated with decreased mortality
      after isolated coronary artery bypass graft surgery in patients already receiving
      aspirin: a propensity-matched study.
AB  - OBJECTIVE: This study was designed to determine the effect of ketorolac on
      mortality after cardiac surgery. DESIGN: A retrospective multivariable analysis
      with propensity matching and propensity scoring. SETTING: A tertiary care
      university-affiliated medical center. PARTICIPANT: Eleven hundred eighty-six
      patients undergoing isolated coronary artery bypass surgery. MAIN RESULTS:
      Between January 1, 2002, and November 1, 2004, 168 patients undergoing isolated
      coronary artery bypass surgery received ketorolac, whereas 1,018 patients did
      not. There were 2 deaths (1%) in the ketorolac group compared with 104 (10%) in
      the nonketorolac group (p < 0.001). Within 90 days of surgery, there was 1 death
      (1%) in the ketorolac group compared with 51 (5%) in the nonketorolac group (p =
      0.01). By Cox modeling, ketorolac use was associated with a 7-fold lower risk of
      death (p = 0.02). In the patients who survived at least 90 days, there was 1
      death (1%) in the ketorolac group compared with 53 (5%) in the nonketorolac group
      (p = 0.01). By Cox modeling, ketorolac use was associated with a 2.4-fold lower
      risk of death (p = 0.03) in the late hazard period. In the propensity-matched
      groups, Kaplan-Meier survival was better in patients who received ketorolac (p =
      0.02). CONCLUSION: The use of ketorolac was associated with a statistically
      significant decrease in mortality at follow-up.

PMID- 18068060
TI  - Role of magnesium sulfate in postoperative pain management for patients
      undergoing thoracotomy.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of magnesium
      sulfate on pain management for post-thoracotomy patients. DESIGN: A prospective,
      randomized, controlled clinical study. SETTING: University hospital.
      PARTICIPANTS: Twenty-four patients undergoing thoracotomy. INTERVENTIONS: After
      thoracotomy operations, patients were assigned to 2 groups. The control group
      received intravenous morphine (0.5 mg/h infusion, 0.3 mg patient-controlled
      anesthesia dose, 15-minute lockout time) via patient-controlled analgesia, and
      the magnesium group received magnesium sulfate (30-mg/kg bolus, 10 mg/kg/h
      infusion for 48 hours) plus the same patient-controlled analgesia protocol.
      MEASUREMENTS AND MAIN RESULTS: Visual analog scale for pain score, sedation
      score, mean arterial pressure, heart rate, and valid and invalid analgesic demand
      were recorded. Serum magnesium levels were determined at postanesthesia care unit
      admission, at 24 hours, and at 48 hours. Side effects were also recorded. There
      were no significant differences between groups with respect to demographics,
      sedation score, and pain score. Cumulative mean morphine consumption was found to
      be higher in the control group compared with the magnesium group at 4, 8, and 48
      hours (5.6 +/- 1 mg v 3.2 +/- 0.6 mg [p < 0.0001], 10.2 +/- 1.8 mg v 7.2 +/- 1.6
      mg [p = 0.0003), and 40.2 +/- 4.5 mg v 34.8 +/- 6.3 mg [p = 0.02], respectively).
      CONCLUSION: Postoperative use of magnesium sulfate reduced opioid consumption for
      pain after thoracotomy operations.

PMID- 18068061
TI  - The acute physiology and chronic health evaluation III outcome prediction in
      patients admitted to the intensive care unit after pneumonectomy.
AB  - PURPOSE: The Acute Physiology and Chronic Health Evaluation (APACHE) III
      prognostic system has not been previously validated in patients admitted to the
      intensive care unit (ICU) after pneumonectomy. The purpose of this study was to
      determine if the APACHE III predicts hospital mortality after pneumonectomy.
      METHODS: A retrospective review of all adult patients admitted to a single
      thoracic surgical intensive care unit after pneumonectomy between October 1994
      and December 2004. Patient demographics, ICU admission day APACHE III score,
      actual and predicted hospital mortality, and length of hospital and ICU stay data
      were collected. Data on preoperative pulmonary function tests and smoking habits
      were also collected. Univariate statistical methods and logistic regression were
      used. The performance of the APACHE III prognostic system was assessed by the
      Hosmer-Lemeshow statistic for calibration and area under receiver operating
      characteristic curve (AUC) for discrimination. RESULTS: There were 417
      pneumonectomies performed during the study period, of which 281 patients were
      admitted to the ICU. The mean age was 61.1 years, and 67.2% were men; 88.2% were
      smokers with a median of 40.0 (interquartile range, 18-62) pack-years of tobacco
      use. The mean APACHE III score on the day of ICU admission was 37.7 (+/- standard
      deviation 17.8), and the mean predicted hospital mortality rate was 6.4% (+/
      10.4). The median (and interquartile range) lengths of ICU and hospital stay were
      1.7 (0.9-3.1) and 9.0 (7.0-17.0) days, respectively. The observed ICU and
      hospital mortality rates were 4.6% (13/281 patients) and 8.2% (23/281),
      respectively. The standardized ICU and hospital mortality ratios with their 95%
      confidence intervals (CIs) were 1.55 (0.71-2.39) and 1.27 (0.75-1.78),
      respectively. There were significant differences in the mean APACHE III score (p
      < 0.001) and the predicted mortality rate (p < .001) between survivors and
      nonsurvivors. In predicting mortality, the AUC of APACHE III prediction was 0.801
      (95% CI, 0.711-0.891), and the Hosmer-Lemeshow statistic was 9.898 with a p value
      of 0.272. Diffusion capacity of the lung for carbon monoxide (DLCO) and
      percentage predicted DLCO were higher in survivors, but the addition of either of
      these variables to a logistic regression model did not improve APACHE III
      mortality prediction. CONCLUSIONS: In patients admitted to the ICU after
      pneumonectomy, the APACHE III discriminates moderately well between survivors and
      nonsurvivors. The calibration of the model appears to be good, although the low
      number of deaths limits the power of the calibration analysis. The use of APACHE
      III data in outcomes research involving patients who have undergone pneumonectomy
      is acceptable.

PMID- 18068062
TI  - Inflation of the distal cuff by saline reduces the incidence of malposition of
      the bronchial tube during lung separation in patients receiving nitrous oxide.
AB  - BACKGROUND: A common problem during lung separation is malposition of the double
      lumen tube (DLT). It was hypothesized that inflation of the distal cuff with
      saline instead of air may reduce the incidence of malposition of the
      endobronchial tube. MATERIALS AND METHODS: Fifty-two patients who were scheduled
      to undergo thoracic surgery with lung separation by a DLT were randomly assigned
      to 1 of 2 groups: the distal cuff was inflated with 2 mL of air in the air group
      (n = 26), whereas the distal cuff was inflated with 1.2 mL of saline in the
      saline group (n = 26). Anesthesia was maintained by isoflurane, 50% oxygen and
      nitrous oxide mixture, and incremental injection of epidural ropivacaine, 0.75%.
      Respiration was controlled by pressure-controlled ventilation. The peak airway
      pressure was maintained between 20 to 25 cmH2O. The position of the bronchial
      cuff was evaluated with a fiberoptic bronchoscope just after intubation and 1 and
      2 hours after intubation by using a 3-point scale: 0, in exactly the same
      position as the previous inspection; 1, not in exactly the same position as that
      in the previous inspection, but there was no possibility that the tube was
      malpositioned; and 2, the cuff looked as if it was going to become herniated or
      dislodged. Signs suggesting malposition such as air leakage, high airway
      pressure, or inflation of the independent lung were recorded. When repositioning
      was required, the anesthesiologist repositioned the DLT using bronchoscopic
      observation or clinical signs. The endpoint of this study was the number of
      patients who required repositioning during surgery. RESULTS: The malposition
      score at 1 hour and 2 hours after intubation was comparable in the 2 groups (0.6
      +/- 0.6 v 0.4 +/- 0.6 and 0.5 +/- 0.8 v 0.2 +/- 0.5, mean +/- standard deviation,
      air group v saline group, 1 hour and 2 hours after positioning, p = 0.27 and p =
      0.33, respectively). However, a significantly higher cumulative number of air
      group patients required repositioning of the tube than saline-group patients
      (13:6, air group:saline group, p = 0.04). CONCLUSION: Inflation of the distal
      cuff with saline may reduce the incidence of malpositioning of DLTs during lung
      separation.

PMID- 18068063
TI  - Clinical and laboratory correlates of excessive and persistent blood glucose
      elevation during cardiac surgery in nondiabetic patients: a retrospective study.
AB  - BACKGROUND: Hyperglycemia during cardiac surgery in nondiabetic patients is a
      common finding associated with increased morbidity and mortality, but its
      predictors have not been studied to date. METHODS: To identify clinical and
      laboratory correlates of excessive and persistent blood glucose (BG) elevation
      during cardiopulmonary bypass (CPB) in nondiabetic patients, the authors reviewed
      195 medical records. After exclusion of patients with preoperative BG >120 mg/dL
      and with missing preoperative BG data, 163 cases were included in the final
      analysis. Patients with BG > or =200 mg/dL during CPB and remaining > or =200
      mg/dL either during or after CPB or at the first postoperative measurement formed
      the study group (n = 35). One case had insufficient data to determine group
      assignment and was not used in comparison. The remaining patients formed the
      control group (n = 127). RESULTS: BG was > or =200 mg/dL at least once
      perioperatively in 114 of 163 (70%) patients. It occurred during CPB in 100 of
      163 (61%) cases and persisted beyond CPB in 35 of 162 (22%) cases. Univariate
      analysis revealed a significant difference between groups in preoperative use of
      angiotensin-converting enzyme (ACE) inhibitors (51% v 29%, p = 0.02), total dose
      of phenylephrine during CPB (14.1 mg +/- 10.6 mg v 10.3 +/- 9.6 mg, p = 0.003)
      and pre-CPB BG (123 +/- 22 mg/dL v 113 +/- 18 mg/dL, p = 0.02). In multivariate
      analysis, ACE inhibitors and pre-CPB BG remained statistically significant.
      CONCLUSIONS: Nondiabetic patients with excessive and persistent BG elevation
      during cardiac surgery are more likely to take ACE inhibitors preoperatively,
      show relatively high pre-CPB BG, and possibly require higher doses of
      vasoconstrictors during CPB.

PMID- 18068064
TI  - Fenoldopam infusion for renal protection in high-risk cardiac surgery patients: a
      randomized clinical study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the renoprotective effects
      of fenoldopam in patients at high risk of postoperative acute kidney injury
      undergoing elective cardiac surgery requiring cardiopulmonary bypass. DESIGN: A
      double-blind randomized clinical trial. SETTING: Hospital. PARTICIPANTS: One
      hundred ninety-three patients. INTERVENTIONS: Patients undergoing cardiac surgery
      were randomly assigned to receive a continuous infusion of fenoldopam, 0.1
      microg/kg/min (95 patients), or placebo (98 patients) for 24 hours. Patients were
      included if at least 1 of the following risk factors was present: preoperative
      serum creatinine > or =1.5 mg/dL, age >70 years, diabetes mellitus, or prior
      cardiac surgery. Serum creatinine and urinary output were measured at baseline
      (T1), 24 hours (T2), and 48 hours after surgery (T3). Acute kidney injury was
      defined as a postoperative serum creatinine level of > or =2 mg/dL with an
      increase in serum creatinine level of 0.7 mg/dL or greater from preoperative to
      maximum postoperative values. MEASUREMENTS AND MAIN RESULTS: Acute kidney injury
      developed in 12 of 95 (12.6%) patients receiving fenoldopam and in 27 of 98
      (27.6%) patients receiving placebo (p = 0.02), whereas renal replacement therapy
      was started in 0 of 95 and 8 of 98 (8.2%) patients, respectively (p = 0.004).
      Serum creatinine was similar at baseline (1.8 +/- 0.4 mg/dL v 1.9 +/- 0.3 mg/dL)
      in the fenoldopam and placebo groups but differed significantly (p < 0.001 and p
      < 0.001) 24 hours (1.6 +/- 0.2 mg/dL v 2.5 +/- 0.6 mg/dL) and 48 hours (1.5 +/-
      0.3 mg/dL v 2.8 +/- 0.4 mg/dL) after the operation. CONCLUSIONS: A 24-hour
      infusion of 0.1 mug/kg/min of fenoldopam prevented acute kidney injury in a high
      risk population undergoing cardiac surgery.

PMID- 18068065
TI  - Platelet mapping and desmopressin reversal of platelet inhibition during
      emergency carotid endarterectomy.

PMID- 18068066
TI  - Valvular heart disease caused by carcinoid syndrome: emphasis on the use of
      intraoperative transesophageal echocardiography.

PMID- 18068068
TI  - Catastrophic cardiac hypokinesis and multiple-organ failure after surgery in a
      patient with an undiagnosed pheochromocytoma: emergency excision of the tumor.

PMID- 18068067
TI  - Induction of anesthesia triggers hypertensive crisis in a patient with
      undiagnosed pheochromocytoma: could rocuronium be to blame?

PMID- 18068069
TI  - Peripheral cardiopulmonary bypass-assisted thymoma resection.

PMID- 18068070
TI  - Cardiovascular collapse during living-directed orthotopic liver transplantation
      associated with the transfusion of contaminated red blood cells.

PMID- 18068071
TI  - Combined general and spinal anesthesia in an infant with single-ventricle
      physiology undergoing anorectoplasty for an imperforate anus.

PMID- 18068072
TI  - Undiagnosed high tracheal bifurcation and laryngomalacia in a case of tetralogy
      of fallot with absent left pulmonary artery for emergency surgery.

PMID- 18068073
TI  - Resistant hypoxemia in an infant with a right ventricle-to-pulmonary artery
      (Sano) shunt.

PMID- 18068074
TI  - Single-lung ventilation for right-sleeve pneumonectomy with a modified nasal RAE
      endotracheal tube.

PMID- 18068075
TI  - Reexpansion pulmonary edema.

PMID- 18068076
TI  - Anesthesia technique for endobronchial ultrasound-guided fine needle aspiration
      of mediastinal lymph node.

PMID- 18068077
TI  - Case 6--2007: massive intraoperative thrombosis and death after recombinant
      activated factor VII administration.

PMID- 18068078
TI  - A rare cause of subtotal airway obstruction during anesthetic induction in a
      patient with facial trauma.

PMID- 18068079
TI  - Errant migrant: an unusual cause of abdominal pain.

PMID- 18068080
TI  - ST-segment changes.

PMID- 18068082
TI  - What are the clinical questions for optimal conduct of deep hypothermic
      circulatory arrest for adult aortic arch repair?

PMID- 18068083
TI  - Success rate, decubitus position, and vagal reflex during a high thoracic
      epidural for coronary artery surgery.

PMID- 18068084
TI  - Anesthesiologists' placement of cannulae for cardiopulmonary bypass.

PMID- 18068085
TI  - Additional information on the pulsatile pressure waveform.

PMID- 18068086
TI  - Fish baffles doctors: scombroid fish poisoning or fish allergy?

PMID- 18068087
TI  - Caution when positioning central venous catheter and its relationship to the
      pericardial reflection.

PMID- 18068090
TI  - Nanotechnology comes of age to trigger the third industrial revolution.

PMID- 18068092
TI  - SERS detection of thrombin by protein recognition using functionalized gold
      nanoparticles.
AB  - We present a method based on surface-enhanced Raman spectroscopy and exploiting a
      protein-protein recognition process able to detect thrombin at subpicomolar
      concentrations. Gold nanoparticles (NPs) were capped with a bifunctional molecule
      capable of forming a covalent link with the aromatic residues of the protein
      moiety. The typical vibrations of the diazo bond established between the
      bifunctional molecule and the target protein are found to be selectively enhanced
      by the conjugated gold NPs, and therefore constitutes the Raman marker. After the
      interaction of functionalized NPs with antithrombin as a sensitive recognition
      element, immobilized on a capture substrate, we have detected thrombin at a
      concentration of about 10(-13) M.

PMID- 18068091
TI  - Development and characterization of hyaluronic acid-anchored PLGA nanoparticulate
      carriers of doxorubicin.
AB  - A novel hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG
      PLGA) copolymer was synthesized and characterized by infrared and nuclear
      magnetic resonance spectroscopy. The nanoparticles of doxorubicin (DOX)-loaded HA
      PEG-PLGA were prepared and compared with monomethoxy(polyethylene glycol) (MPEG)
      PLGA nanoparticles. Nanoparticles were prepared using drug-to-polymer ratios of
      1:1 to 1:3. Drug-to-polymer ratio of 1:1 is considered the optimum formulation on
      the basis of low particle size and high entrapment efficiency. The optimized
      nanoparticles were characterized for morphology, particle size measurements,
      differential scanning calorimetry, x-ray diffractometer measurement, drug
      content, hemolytic toxicity, subacute toxicity, and in vitro DOX release. The in
      vitro DOX release study was performed at pH 7.4 using a dialysis membrane. HA-PEG
      PLGA nanoparticles were able to sustain the release for up to 15 days. The tissue
      distribution studies were performed with DOX-loaded HA-PEG-PLGA and MPEG-PLGA
      nanoparticles after intravenous (IV) injection in Ehrlich ascites tumor-bearing
      mice. The tissue distribution studies showed a higher concentration of DOX in the
      tumor as compared with MPEG-PLGA nanoparticles. The in vivo tumor inhibition
      study was also performed after IV injection of DOX-loaded HA-PEG-PLGA
      nanoparticles up to 15 days. DOX-loaded HA-PEG-PLGA nanoparticles were able to
      deliver a higher amount of DOX as compared with MPEG-PLGA nanoparticles. The DOX
      loaded HA-PEG-PLGA nanoparticles reduced tumor volume significantly as compared
      with MPEG-PLGA nanoparticles.

PMID- 18068093
TI  - From bench to bedside: successful translational nanomedicine: highlights of the
      Third Annual Meeting of the American Academy of Nanomedicine.
AB  - The Third Annual Meeting of the American Academy of Nanomedicine (AANM) was held
      at the University of California San Diego, in San Diego, California during
      September 7-8, 2007. The meeting was focused on successful translational
      nanomedicine: from bench to bedside. There were four keynote lectures and eight
      scientific symposiums in this meeting. The researchers and investigators reported
      the results and process of current nanomedicine research and approaches to
      clinical applications. The meeting provided exciting information for nanomedicine
      clinical-related researches and strategy for further development of nanomedicine
      research which will be benefits to clinical practice.

PMID- 18068094
TI  - Engineering and characterization of a mouse/human chimeric anti-phencyclidine
      monoclonal antibody.
AB  - Previously, our laboratory produced a high affinity, anti-phencyclidine (PCP)
      murine monoclonal antibody (mAb6B5) that also binds other PCP-like
      arylcyclohexylamines. In this project, mAb6B5 is engineered into a mouse/human
      chimera (ch-mAb6B5) to assess the feasibility of developing it into a medication
      for PCP and PCP-like drug abuse. To create ch-mAb6B5, the light and heavy chain
      constant regions of mAb6B5 were replaced with human kappa and IgG(2) constant
      regions in order to decrease its potential immunogenicity in humans. To be an
      effective anti-PCP medication, ch-mAb6B5 must retain the critical immunochemical
      binding properties of mAb6B5. Expression vectors containing ch-mAb6B5 light chain
      and heavy chain cDNA were constructed and expressed in the murine myeloma cell
      line P3X63-Ag8.653. Immunoassays confirm that ch-mAb6B5 is indeed a chimera,
      composed of mAb6B5's PCP-binding variable domains and human kappa and IgG
      constant regions. Radioimmunoassays show that ch-mAb6B5 has the same drug-binding
      profile as mAb6B5. Ch-mAb6B5 and mAb6B5 bind PCP with a K(D) of 0.67 nM and 1.17
      nM (respectively) and bind PCP-like arylcyclohexylamines 1-[1-(2
      thienyl)cyclohexyl]piperidine and N-ethyl-1-phenylcyclohexylamine with similar
      specificity. Additionally, ch-mAb6B5 and mAb6B5 have the same calculated
      isoelectric points and molecular weights, critical properties in antigen-antibody
      interactions. These data demonstrate that mouse/human ch-mAb6B5, a "more human"
      version of murine mAb6B5, retains mAb6B5's unique drug-binding properties. This
      work supports our continued efforts to develop ch-mAb6B5 into a medication for
      PCP and PCP-like drug abuse - introducing the intriguing possibility of using a
      single therapeutic mAb for treating a class of abused drugs.

PMID- 18068095
TI  - Enhancement of antitumor activity of OK-432 (picibanil) by Triton X-114 phase
      partitioning.
AB  - OK-432 (Picibanil), a Streptococcal immunotherapeutic agent, has been used for
      immunotherapy of various cancers as a biological response modifier (BRM).
      However, OK-432 contains multiple components consisting of immunotherapeutic ones
      and contaminants which may weaken the effects or exert side-effects. In this
      study, we investigated extraction of contaminants from OK-432 using Triton X-114
      (TX-114)-water phase partitioning and examined an antitumor effect of the
      resulting preparation. OK-432 was subjected to TX-114 partitioning to give
      residual precipitate designated as OK-TX-ppt. OK-TX-ppt exerted no TLR2-mediated
      activity, but induced interleukin (IL)-6 in human PBMC. OK-TX-ppt also induced
      tumor necrosis factor (TNF)-alpha, IL-10, IL-12, and interferon (IFN)-gamma in
      PBMC. Moreover, IFN-gamma-inducing activity of OK-TX-ppt was significantly higher
      and IL-10 production was lower than that of OK-432. In tumor-bearing mice model,
      administration of OK-TX-ppt i.p. extended the survival time of Meth-A-bearing
      mice compared to OK-432. OK-TX-ppt also increased the levels of IL-12 and IFN
      gamma in mouse spleen cells in vitro. These results indicated that TX-114
      partitioning removed some contaminants, which attenuates the antitumor effect,
      from OK-432 and increase the immunotherapeutic effects of OK-432.

PMID- 18068096
TI  - Dextran sulphate sodium induces acute colitis and alters hepatic function in
      hamsters.
AB  - Dextran sulphate sodium (DSS)-induced colitis in rodents is an experimental model
      for human inflammatory bowel disease (IBD). The aim of this study was to
      characterize the effect of DSS in hamster colon and liver. DSS (2-5%) was
      administrated in the drinking water for 4-6 days. Clinical symptoms were recorded
      daily, inflammatory and fatty acid-related metabolic markers were assessed in
      plasma, colon and liver. Six days of 3 or 5% DSS induced a severe wasting
      disease, whereas 2.5% DSS induced a colonic inflammation without severe systemic
      adverse effects. The systemic inflammatory response was characterized by an
      inverse production of albumin and the acute phase protein haptoglobin. The
      colonic inflammatory response was confined to the proximal colon, manifested by a
      high macroscopic inflammatory score, increased colon weight and expression of IL
      1beta, IL-6 and iNOS, infiltration of inflammatory cells and epithelial
      disruption. In contrast, only a low/mild inflammatory response was observed in
      the distal colon of DSS-exposed hamsters. Significant hepatic-related metabolic
      alterations were also observed, with elevation of plasma triglycerides and
      increased liver expression of lipoprotein lipase and reduced expression of acyl
      CoA oxidase and cytochrome P450A. Although liver weight was significantly
      reduced, no histopathological signs of inflammation or tissue damage were
      observed. In summary, hamsters exposed to 2.5% DSS for 6 days develop acute
      colitis resembling murine DSS-induced colitis. In addition, DSS-exposed hamster
      showed alterations in hepatic fatty acids metabolism resembling human IBD,
      suggesting that the model can potentially be used for target discovery and
      validation of hepatic-related metabolic alterations.

PMID- 18068097
TI  - Enhanced susceptibility to Trichuris muris infection of B10Br mice treated with
      the probiotic Lactobacillus casei.
AB  - The aim of this paper was to establish a suitable model for exploring the
      immunoregulatory bases of the interaction of probiotics with intestinal helminth
      infections. The mouse whipworm Trichuris muris, was used in the susceptible B10Br
      mice. Mice were treated orally with either viable or dead probiotic L. casei and
      1 week later they were submitted to a challenge infection of 400 embryonated eggs
      of T. muris. Treatment with either viable or dead bacteria significantly
      increased the intestinal worm burden by day 22 post-infection. Viable L. casei
      significantly reduced the levels of faecal IgA induced by challenge infection.
      The proliferation response of MNL cells against mitogens was significantly
      reduced by dead bacteria and abrogated by viable bacteria. Furthermore the
      presence of the probiotic was associated to a significant decrease in IFN-gamma,
      TNF-alpha, IL-4 and Il-13 with no effect on IL-5 in both MNL and PP with regard
      to challenge control infection. The presence of L. casei did not significantly
      modify the proportion of CD4(+) and CD8(+) cells in both MLN and PP. In summary,
      in the susceptible B10Br mouse strain the presence of probiotic L. casei is
      associated to an increased susceptibility to infection by the intestinal whipworm
      T. muris. The mechanisms underlying this evidence could be related to the
      deactivation of TNF-alpha dependent Th2 effector responses against T. muris due
      to the strong down-regulation of this cytokine that is induced by the probiotic
      agent.

PMID- 18068098
TI  - Anti-tumor metastatic activity of beta-glucan purified from mutated Saccharomyces
      cerevisiae.
AB  - The beta-glucans isolated from Saccharomyces cerevisiae (S. cerevisiae) enhance
      the innate immune system, but there is little evidence for its antitumor
      activity. To examine the antitumor and immunostimulating activities of beta
      glucan (IS-2) purified from mutated S. cerevisiae, we made an experiment on
      innate immune response against metastasis of cancer cells by comparing with the
      beta-glucan from wild-type S. cerevisiae. In experimental lung metastasis of
      colon 26-M3.1 carcinoma or B16-BL6 melanoma cells, prophylactic administration of
      beta-glucan purified from mutated S. cerevisiae significantly inhibited lung
      metastasis in a dose-dependent manner. Furthermore, therapeutic administration of
      IS-2 also significantly inhibited the colon 26-M3.1 cell growth in mice. In an
      assay of liver and spleen metastasis produced by i.v. inoculation of L5178Y-ML25
      lymphoma cells, IS-2 also significantly inhibited metastasis in CDF1 mice.
      Furthermore, pretreatment with IS-2 two days before tumor inoculation
      significantly prolonged the survival time of tumor-bearing mice. In an in vitro
      cytotoxicity analysis, IS-2 (up to 100 microg/ml) did not affect the growth of
      colon 26-M3.1 cells. In contrast, IS-2 enhanced splenocyte proliferating activity
      in a dose-dependent manner. Peritoneal macrophages stimulated with IS-2 produced
      various cytokines, such as IL-1beta, IFN-gamma, and IL-12. In addition, treatment
      with IS-2 (20 microg/mouse) induced tumoricidal activity of peritoneal
      macrophages against colon 26-M3.1 cells. In an assay for natural killer (NK) cell
      activity, IS-2 (20 microg/mouse, i.v.) significantly augmented NK cytotoxicity
      against Yac-1 tumor cells at 2 days after IS-2 treatment. The depletion of NK
      cells by injection of rabbit anti-asialo GM1 serum abolished the inhibitory
      effect of IS-2 on lung metastasis of colon 26-M3.1 cells. These data suggest that
      IS-2 inhibits tumor metastasis via activation of macrophages and NK cells.

PMID- 18068099
TI  - Macrophage immunomodulatory activity of polysaccharides isolated from Glycyrrhiza
      uralensis Fish.
AB  - The objective of this study was to evaluate the immunomodulatory effects of the
      purified glycyrrhiza polysaccharides (GP) on the activity of macrophages. A
      purified fraction of water-soluble polysaccharides, with estimated molecular
      weight of 10 kDa, was isolated from Glycyrrhiza uralensis Fish using ion exchange
      and size exclusion chromatography. The results indicate that GP increased the
      pinocytic activity, the production of nitric oxide (NO), interleukin-1 (IL-1), IL
      6 and IL-12 in a dose-dependent manner. The production of IL-1 was induced by GP
      at a dose of 10 microg/mL; but, NO, IL-6 and IL-12 was significantly induced at
      100 microg/mL. A time-dependent enhancement showed that the production of IL-1,
      NO and IL-12 were significantly increased within 6 h. Superoxide anion (O(2)(-))
      production by macrophages from GP-treated mice was higher than that of cells from
      untreated mice. Moreover, cells from both untreated and treated mice responded to
      phorbol 12-myristate 13-acetate (PMA) treatment; however, the O(2)(-) production
      was higher in the cells from treated mice than that of cells from untreated mice.
      Our data suggest that the beneficial therapeutic effects of GP may be attributed
      partly to its ability to modulate macrophage immune functions.

PMID- 18068100
TI  - Effects of Astragalus polysaccharides (APS) on the expression of immune response
      genes in head kidney, gill and spleen of the common carp, Cyprinus carpio L.
AB  - For fish immune defences, cytokines and anti-microbial peptides (lysozyme) in
      circulating system play important roles. In the present study, the effects of
      Astragalus polysaccharides (APS) injection on gene expression of interleukin
      1beta (IL-1beta), tumor necrosis factoralpha (TNF-alpha) and lysozyme-C in the
      head kidney, gill and spleen of common carp were determined using semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR). After
      injection of APS, IL-1beta mRNA level increased in a dose-dependent manner in the
      head kidney, while no significant changes were found in the gill and spleen. High
      dose of APS up regulated TNF-alpha transcription in the gill and spleen, while
      TNF-alpha mRNA level decreased significantly in the head kidney of low dose of
      APS. Lysozyme-C mRNA levels were up regulated in the gill of low dose of APS and
      spleen of middle dose of APS. No effect of the APS on lysozyme-C expression was
      observed in head kidney. These results constitute a first step toward the
      understanding of APS effect on cytokines and immune-related gene expression in
      different organs of common carp.

PMID- 18068101
TI  - Alteration of enzymatic properties of cell-surface antigen CD38 by agonistic anti
      CD38 antibodies that prolong B cell survival and induce activation.
AB  - Leukocyte cell-surface antigen CD38 is a single-transmembrane protein. CD38
      ligation by anti-CD38 antibodies triggers the growth or apoptosis of immune
      cells. Although the extracellular domain of CD38 has multifunctional catalytic
      activities including NAD(+) glycohydrolase and cyclase, the CD38-mediated cell
      survival or death appears to be independent of its catalytic activity. It is
      proposed that a conformational change of CD38 triggers the signalling. The
      conformational change of CD38 could influence its catalytic activity. However,
      the agonistic anti-CD38 antibody that alters the catalytic activity of CD38 has
      not been reported so far. In the present study, we demonstrated that two
      agonistic anti-mouse CD38 mAbs (CS/2 and clone 90) change the catalytic
      activities of CD38. CS/2 was clearly more potent than clone 90 in prolonging B
      cell survival and activation. CS/2 inhibited the NAD(+) glycohydrolase activity
      of both the isolated extracellular domain of CD38 (FLAG-CD38) and cell-surface
      CD38. Kinetic analysis suggested a non-competitive inhibition. On the other hand,
      clone 90 stimulated the NAD(+) glycohydrolase activity of FLAG-CD38 and had
      little effect on the NAD(+) glycohydrolase activity of cell-surface CD38. CS/2
      and clone 90 had no effect on the cyclase activity of FLAG-CD38 and inhibited the
      cyclase activity of cell-surface CD38. Accordingly, these agonistic antibodies
      probably induce the conformational changes of CD38 that are evident in the
      distinct alterations of the catalytic site. The antibodies will be useful tools
      to analyze the conformational change of CD38 in the process of triggering B cell
      survival and the activation signal.

PMID- 18068102
TI  - Leuprolide--a GnRH agonist--prevents restraint stress-induced immunosuppression
      via sex steroid-independent peripheral mechanism in mice.
AB  - Gonadotropin-releasing hormone (GnRH) and sex steroids are known to modulate the
      immune system. To find out whether GnRH analogue can be useful to prevent the
      stress-induced immunosuppression, mice were treated with leuprolide (50
      microg/mouse, s.c.) 30 min prior to restraint stress and immunological parameters
      were studied. Leuprolide prevented stress-induced decrease in relative weights of
      thymus, total leukocyte count and sheep red blood cells challenged humoral and
      cell-mediated immune reaction. Prior administration of GnRH antagonist (10
      ng/mouse) through i.c.v. route did not alter the immunological effects of
      leuprolide. Further, the observed effect of leuprolide remained unaffected in
      castrated and ovariectomized mice. Thus, the investigations revealed that
      leuprolide prevented stress-induced immunosuppression through a peripheral
      mechanism, which is independent of systemic sex steroids.

PMID- 18068103
TI  - Contribution of extracellular signal-regulated kinases to the IL-1-induced growth
      inhibition of human melanoma cells A375.
AB  - The role of ERK1/2 in the IL-1-induced growth inhibition was investigated using
      human melanoma A375-6 cells. A selective inhibitor of ERK1/2 pathway, PD98059 and
      a selective inhibitor of p38MAPK, SB203580 each alone significantly reversed the
      IL-1-induced growth inhibition of A375-6 cells. Co-treatment with PD98059 and
      SB203580 completely reversed the IL-1-induced growth inhibition. ERK1/2 was
      constitutively activated in A375-6 cells, and IL-1 further augmented ERK
      activation. Antiproliferative effect of IL-1 was attenuated by the expression of
      dominant negative form of ERK2. IL-1 induced cell cycle arrest in G(0)/G(1)
      phase, expression of p21 and p27 proteins, and down-regulation of cyclin D/cyclin
      dependent kinase (CDK) 2 and CDK4 activities. These effects of IL-1 were reversed
      by PD98059. PD98059 also reversed the IL-1-induced hypophosphorylation of RB
      protein (pRB) and down-regulation of E2F activity. These findings demonstrate
      that ERK1/2 contribute to the IL-1-induced growth inhibition through induction of
      CDK inhibitors, down-regulation of CDK activity, pRB phosphorylation and E2F
      activity.

PMID- 18068104
TI  - Intact protein core structure is essential for protein-binding, mononuclear cell
      proliferating, and neutrophil phagocytosis-enhancing activities of normal human
      urinary Tamm-Horsfall glycoprotein.
AB  - Tamm-Horsfall glycoprotein (THP) is synthesized in the particular sites of renal
      tubules acting as a defense molecule in the urinary system. In the present study,
      we found that THP contained high amount of Siaalpha(2,3)Gal/GalNAc, moderate
      amount of beta(1,4)GlcNAc oligomers and GlcNAc/branched mannose, and low amount
      of mannose residues, but no Siaalpha(2,6)Gal/GalNAc, in the side-chains of the
      molecule. THP exhibited high binding affinity with human TNF-alpha, IgG, C1q and
      BSA, moderate binding affinity with IL-8, and low binding affinity with IL-6 and
      IFN-gamma. For exploring the role of carbohydrate side-chains and protein core in
      the protein-binding and cell-stimulating activities, THP was enzyme-digested with
      carbohydrate-specific [neuraminidase (Nase), beta-galactosidase (Gase)], protein
      specific [V8 protease (V8), proteinase K (PaseK)] and glycoconjugate-specific
      [carboxypeptidase Y (Case), O-sialoglycoprotein endopeptidase (Oase)] degrading
      enzymes. We found that THP digested with V8, Oase, and PaseK, significantly
      reduced its protein-binding, mononuclear cell proliferating, and neutrophil
      phagocytosis-enhancing activities. These results suggest that the intact protein
      core structure, but not carbohydrate side-chains, is essential for pleotropic
      functions of THP molecule.

PMID- 18068105
TI  - Janus kinase 3 inhibitor WHI-P154 in macrophages activated by bacterial
      endotoxin: differential effects on the expression of iNOS, COX-2 and TNF-alpha.
AB  - Bacterial endotoxin is a potent inducer of inflammatory response, including the
      induction of inducible nitric oxide synthase (iNOS) expression and nitric oxide
      (NO) production, and the expression of cyclo-oxygenase (COX)-2 and tumor necrosis
      factor (TNF)-alpha in inflammatory cells. In the present study, we investigated
      the effects of pharmacological inhibition of Janus kinase (JAK) 3 on the
      production of these proinflammatory molecules in macrophages exposed to bacterial
      endotoxin (lipopolysaccharide; LPS). JAK3 inhibitors WHI-P154 (4-(3'-bromo-4'
      hydroxylphenyl)-amino-6,7-dimethoxyquinazoline) and its derivative WHI-P131
      inhibited LPS-induced iNOS expression and NO production in a dose-dependent
      manner. WHI-P154 inhibited the activation of signal transducer and activator of
      transcription (STAT) 1 and the expression of iNOS mRNA but it had no effect on
      iNOS mRNA decay when determined by actinomycin D assay. The JAK3 inhibitor had no
      effect on COX-2 expression, and TNF-alpha production was slightly inhibited only
      at higher drug concentrations (30 microM). In addition, WHI-P154 inhibited iNOS
      expression and NO production also in human epithelial cells. Our results suggest
      that JAK3 inhibition modulates human and murine iNOS expression and NO production
      in response to inflammatory stimuli.

PMID- 18068106
TI  - Defensive effects of a fucoidan from brown alga Undaria pinnatifida against
      herpes simplex virus infection.
AB  - Fucoidan, a sulfated polysaccharide isolated from an edible brown alga Undaria
      pinnatifida, was previously shown to be a potent inhibitor of the in vitro
      replication of herpes simplex virus type 1 (HSV-1). HSV-1 is a member of herpes
      viruses that cause infections ranging from trivial mucosal ulcers to life
      threatening disorders in immunocompromised hosts. In the in vivo conditions, the
      replication of HSV-1 is controlled under the immunoresponse coordinated by both
      the innate and adaptive immune systems. In the present study, the effects of the
      fucoidan were examined on in vivo viral replication and the host's immune defense
      system. Oral administration of the fucoidan protected mice from infection with
      HSV-1 as judged from the survival rate and lesion scores. Phagocytic activity of
      macrophages and B cell blastogenesis in vitro were significantly stimulated by
      the fucoidan, while no significant change in the release of NO(2)(-) by
      macrophages was observed. In in vivo studies, oral administration of the fucoidan
      produced the augmentation of NK activity in HSV-1-infected mice immunosuppressed
      by 5-fluorouracil treatment. CTL activity in HSV-1-infected mice was also
      enhanced by oral administration of the fucoidan. The production of neutralizing
      antibodies in the mice inoculated with HSV-1 was significantly promoted during
      the oral administration of the fucoidan for 3 weeks. These results suggested that
      oral intake of the fucoidan might take the protective effects through direct
      inhibition of viral replication and stimulation of both innate and adaptive
      immune defense functions.

PMID- 18068107
TI  - A carbohydrate fraction, AIP1 from Artemisia iwayomogi suppresses pulmonary
      eosinophilia and Th2-type cytokine production in an ovalbumin-induced allergic
      asthma. Down-regulation of TNF-alpha expression in the lung.
AB  - Asthma is a chronic inflammatory disease of the airways characterized by
      reversible airway obstruction, airway hyperreactivity, and remodeling of the
      airways. The incidence of asthma is on the rise despite ongoing intensive asthma
      research. Artemisia iwayomogi, a member of the Compositae, is a perennial herb
      easily found around Korea and has been used as a traditional anti-inflammatory
      medicine in liver diseases. We investigated suppressive effects of AIP1, a water
      soluble carbohydrate fraction from A. iwayomogi on ovalbumin-induced allergic
      asthma in BALB/c mice and studied the possible mechanisms of its anti-allergic
      action. AIP1 significantly reduced pulmonary eosinophilia and Th2 cytokine
      expression in the lungs as well as serum IgE levels. Flow cytometric analysis of
      lung-infiltrating cells showed that the surface levels of CD11c and MHC II in
      CD11c+MHC II+ cells, potent dendritic cells, decreased in animals treated with
      AIP1. Expression of TNF-alpha, one of several proinflammatory cytokines released
      into the airway during episodes of asthma, was down-regulated by AIP1 injection,
      suggesting that reduced expression of TNF-alpha could account for the suppression
      of pulmonary eosinophilia and Th2-type cytokine production by AIP1.

PMID- 18068108
TI  - Roxithromycin inhibits the effector phase of delayed-type hypersensitivity.
AB  - In the present paper, the effect of roxithromycin on delayed-type
      hypersensitivity (DTH) was evaluated. Roxithromycin had no effect on sheep red
      blood cells (SRBC)-induced food pad swelling when orally administered in
      induction phase, whereas it suppressed the SRBC-induced DTH reaction and 2,4,6
      Trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) significantly
      when administered to mice in effector phase. For the sustained-CHS model induced
      by multi-challenge with TNCB, roxithromycin also inhibited the ear swelling when
      exposed to mice in three effector phases while showed no inhibitory effect on CHS
      by continuous treatment. Administration of this antibiotic in effector phase also
      down-regulated the MMP-9 activity and the higher in vitro survival of splenocytes
      from SRBC-challenged mice. Furthermore, this drug inhibited the gene expression
      of T-helper type 1 (Th1) cytokines such as IL-2 and IFN-gamma of lymph node cells
      from mice immuned by TNCB or of Con A-stimulated spleen cells. In addition,
      roxithromycin administered in vivo decreased the concanavalin A (Con A)-induced
      splenocyte proliferation without affecting the cell survival in vitro. These
      results suggest that roxithromycin might alleviate DTH reaction at least by
      suppressing the function and survival of effector T cells.

PMID- 18068109
TI  - Determination of active enzyme concentration using activity-based probes and
      direct mass spectrometric readout.
AB  - Activity-based probes (ABPs) are specific covalent inhibitors developed for
      different classes of enzymes. We have titrated a serine protease and a lipase
      with their specific ABPs and measured the extent of inhibition using
      nanoelectrospray mass spectrometry (nanoESI-MS). Because ABPs only interact with
      the active enzyme form, the approach allows to accurately measure the active
      enzyme concentration in solution. This is even possible in the presence of
      contaminants. The concentrations of the two enzymes were also investigated by UV
      spectroscopy, which appears to give higher concentrations than those measured
      with the active site titration method.

PMID- 18068110
TI  - Molecular and biochemical characterization of benzalacetone synthase and chalcone
      synthase genes and their proteins from raspberry (Rubus idaeus L.).
AB  - Two new members of the polyketide synthase (PKS) gene family (RiPKS4 and RiPKS5)
      were cloned from raspberry fruits (Rubus idaeus L., cv Royalty) and expressed in
      Escherichia coli. Characterization of the recombinant enzyme products indicated
      that RiPKS4 is a bifunctional polyketide synthase producing both 4
      hydroxybenzalacetone and naringenin chalcone. The recombinant RiPKS4 protein,
      like the native protein from raspberry fruits [W. Borejsza-Wysocki, G. Hrazdina,
      Plant Physiol. 1996;110: 791-799] accepted p-coumaryl-CoA and ferulyl-CoA as
      starter substrates and catalyzed the formation of both naringenin chalcone, 4
      hydroxy-benzalacetone and 3-methoxy-4-hydroxy-benzalacetone. Although activity of
      RiPKS4 was higher with ferulyl-CoA than with p-coumaryl-CoA, the corresponding
      product, 3-methoxy-4-hydroxy phenylbutanone could not be detected in raspberries
      to date. Sequence analysis of the genes and proteins suggested that this feature
      of RiPKS4 was created by variation in the C-terminus due to DNA recombination at
      the 3' region of its coding sequence. RiPKS5 is a typical chalcone synthase (CHS)
      that uses p-coumaryl-CoA only as starter substrate and produces naringenin
      chalcone exclusively as the reaction product.

PMID- 18068111
TI  - ATP synthesis without R210 of subunit a in the Escherichia coli ATP synthase.
AB  - Interactions between subunit a and oligomeric subunit c are essential for the
      coupling of proton translocation to rotary motion in the ATP synthase. A pair of
      previously described mutants, R210Q/Q252R and P204T/R210Q/Q252R [L.P. Hatch, G.B.
      Cox and S.M. Howitt, The essential arginine residue at position 210 in the a
      subunit of the Escherichia coli ATP synthase can be transferred to position 252
      with partial retention of activity, J. Biol. Chem. 270 (1995) 29407-29412] has
      been constructed and further analyzed. These mutants, in which the essential
      arginine of subunit a, R210, was switched with a conserved glutamine residue,
      Q252, are shown here to be capable of both ATP synthesis by oxidative
      phosphorylation, and ATP-driven proton translocation. In addition, lysine can
      replace the arginine at position 252 with partial retention of both activities.
      The pH dependence of ATP-driven proton translocation was determined after
      purification of mutant enzymes, and reconstitution into liposomes. Proton
      translocation by the lysine mutant, and to a lesser extent the arginine mutant,
      dropped off sharply above pH 7.5, consistent with the requirement for a positive
      charge during function. Finally, the rates of ATP synthesis and of ATP-driven
      proton translocation were completely inhibited by treatment with DCCD (N,N'
      dicyclohexylcarbodiimide), while rates of ATP hydrolysis by the mutants were not
      significantly affected, indicating that DCCD modification disrupts the F(1)-F(o)
      interface. The results suggest that minimal requirements for proton translocation
      by the ATP synthase include a positive charge in subunit a and a weak interface
      between subunit a and oligomeric subunit c.

PMID- 18068113
TI  - Insight into the location and dynamics of the annexin A2 N-terminal domain during
      Ca(2+)-induced membrane bridging.
AB  - Annexin A2 (AnxA2) is a Ca(2+)- and phospholipid-binding protein involved in many
      cellular regulatory processes. Like other annexins, it is constituted by two
      domains: a conserved core, containing the Ca(2+) binding sites, and a variable N
      terminal segment, containing sites for interactions with other protein partners
      like S100A10 (p11). A wealth of data exists on the structure and dynamics of the
      core, but little is known about the N-terminal domain especially in the Ca(2+)
      induced membrane-bridging process. To investigate this protein region in the
      monomeric AnxA2 and in the heterotetramer (AnxA2-p11)(2), the reactive Cys8
      residue was specifically labelled with the fluorescent probe acrylodan and the
      interactions with membranes were studied by steady-state and time-resolved
      fluorescence. In membrane junctions formed by the (AnxA2-p11)(2) heterotetramer,
      the flexibility of the N-terminal domain increased as compared to the protein in
      solution. In "homotypic" membrane junctions formed by monomeric AnxA2, acrylodan
      moved to a more hydrophobic environment than in the protein in solution and the
      flexibility of the N-terminal domain also increased. In these junctions, this
      domain is probably not in close contact with the membrane surface, as suggested
      by the weak quenching of acrylodan observed with doxyl-PCs, but pairs of N
      termini likely interact, as revealed by the excimer-forming probe pyrene
      maleimide bound to Cys8. We present a model of monomeric AnxA2 N-terminal domain
      organization in "homotypic" bridged membranes in the presence of Ca(2+).

PMID- 18068112
TI  - Docosahexaenoic acid alters the size and distribution of cell surface
      microdomains.
AB  - We recently generated nutritional data suggesting that chemoprotective dietary n
      3 polyunsaturated fatty acids (n-3 PUFA) are capable of displacing acylated
      proteins from lipid raft microdomains in vivo [D.W. Ma, J. Seo, L.A. Davidson,
      E.S. Callaway, Y.Y. Fan, J.R. Lupton, R.S. Chapkin, n-3 PUFA alter caveolae lipid
      composition and resident protein localization in mouse colon, FASEB J. 18 (2004)
      1040-1042; Y.Y. Fan, L.H. Ly, R. Barhoumi, D.N. McMurray, R.S. Chapkin, Dietary
      docosahexaenoic acid suppresses T cell protein kinase Ctheta lipid raft
      recruitment and IL-2 recruitment, J. Immunol. 173 (2004) 6151-6160]. A primary
      source of very long chain n-3 PUFA in the diet is derived from fish enriched with
      docosahexaenoic acid (DHA, 22:6n-3). In this study, we sought to determine the
      effect of DHA on cell surface microdomain organization in situ. Using immuno-gold
      electron microscopy of plasma membrane sheets coupled with spatial point analysis
      of validated microdomain markers, morphologically featureless microdomains were
      visualized in HeLa cells at high resolution. Clustering of probes within
      cholesterol-dependent (GFP-tH) versus cholesterol-independent (GFP-tK)
      nanoclusters was differentially sensitive to n-3 PUFA treatment of cells.
      Univariate K-function analysis of GFP-tH (5 nm gold) revealed a significant
      increase in clustering (p<0.05) by pre-treatment with DHA and linoleic acid (LA,
      18:2(Delta9,12)) compared to control fatty acids; whereas LA significantly
      (p<0.05) reduced GFP-tK clustering. These novel data suggest that the plasma
      membrane organization of inner leaflets is fundamentally altered by PUFA
      enrichment. We speculate that our findings may help define a new paradigm to
      better understand the complexity of n-3 PUFA modulation of signaling networks.

PMID- 18068114
TI  - Nuclear localized protein-1 (Nulp1) increases cell death of human osteosarcoma
      cells and binds the X-linked inhibitor of apoptosis protein.
AB  - Nuclear localized protein-1 (Nulp1) is a recently identified gene expressed in
      mouse and human tissues particularly during embryonic development. Nulp1 belongs
      to the family of basic helix-loop-helix (bHLH) proteins that are important in
      development. The precise function of Nulp1 in cells is however not known. We
      observed that overexpression of Nulp1 induces a large increase in cell death of
      human osteosarcoma Saos2 cells with DNA fragmentation. In mouse N2A neuroblastoma
      cells Nulp1 affected cell proliferation and sensitized cells towards death
      induced by staurosporine. Staining using a novel antibody localized Nulp1 mainly
      to the cell nucleus and to some extent to the cytoplasm. Nulp1 binds the X-linked
      inhibitor of apoptosis protein (XIAP) and this interaction was increased during
      cell death. These results indicate that Nulp1 plays a role in cell death control
      and may influence tumor growth.

PMID- 18068115
TI  - Regulation of the paracellular Na+ and Cl- conductances by the NaCl-generated
      osmotic gradient in a manner dependent on the direction of osmotic gradients.
AB  - In the present study, we investigated the effect of osmolality on the
      paracellular ion conductance (Gp) composed of the Na(+) conductance (G(Na)) and
      the Cl(-) conductance (G(Cl)). An osmotic gradient generated by NaCl with
      relatively apical hypertonicity (NaCl-absorption-direction) induced a large
      increase in the G(Na) associated with a small increase in the G(Cl), whereas an
      osmotic gradient generated by NaCl with relatively basolateral hypertonicity
      (NaCl-secretion-direction) induced small increases in the G(Na) and the G(Cl).
      These increases in the Gp caused by NaCl-generated osmotic gradients were
      diminished by the application of sucrose canceling the NaCl-generated osmotic
      gradient. The osmotic gradient generated by apical [corrected] application of
      sucrose without any NaCl gradients had little effects on the Gp. However, this
      apical [corrected] application of sucrose produced a precondition drastically
      quickening the time course of the action of the NaCl-generated osmotic gradient
      on the Gp. Further, we found that application of the basolateral hypotonicity
      generated by reduction of NaCl concentration shifted the localization of claudin
      1 to the apical from the lateral [corrected] side. These results indicate that
      the osmotic gradient regulates the paracellular ion conductive pathway of tight
      junctions via a mechanism dependent on the direction of NaCl gradients associated
      with a shift of claudin-1 localization to the apical side in renal A6 epithelial
      cells.

PMID- 18068116
TI  - Sequence-specific binding of DNA and RNA to immobilized Nickel ions.
AB  - Immobilization of divalent Nickel cations provides a tool for affinity
      purification of proteins containing hexahistidine tags. During experiments to
      generate single-stranded DNA aptamers to immobilized proteins we inadvertently
      identified DNA sequences with affinity for Nickel-nitrilotriacetic acid (Ni(2+)
      NTA) magnetic beads. Analysis of these aptamers revealed that affinity for the
      Ni(2+)-NTA support requires only single-stranded sequences with multiple
      adenosine residues. Bound nucleic acids can be eluted with imidazole. A single
      stranded dA(20) affinity tag (but not other homopolymer sequences) is sufficient
      for immobilization of double-stranded DNA PCR products on Ni(2+)-NTA magnetic
      beads. Addition of an rA(20) sequence to an RNA transcript allowed its affinity
      capture on Ni(2+)-NTA magnetic beads, suggesting an approach for purification of
      poly(A) mRNA.

PMID- 18068117
TI  - NMR structure of an intracellular third loop peptide of human GABA(B) receptor.
AB  - GABA(B) receptor is a G protein-coupled receptor for GABA and drug target for
      neurological and psychiatric disorders. From the analysis of GTPgammaS binding
      assay, we found that a synthesized peptide (GABAb: ETKSVSTEKINDHR) corresponding
      to the intracellular third loop region of metabotropic GABA(B) receptor could
      activate G(i) protein alpha subunit directly. The three dimensional molecular
      structure of the peptide in SDS-d(25) micelles was determined by 2D (1)H-NMR
      spectroscopy. GABAb peptide formed an alpha helical structure and a positive
      charge cluster at the C-terminal site. These structural features were also found
      in several other G protein activating peptides. From the comparison among these
      peptides, we found that peptides with high helical content show the high
      activity.

PMID- 18068118
TI  - Thiol reactivity as a sensor of rotation of the converter in myosin.
AB  - Smooth muscle myosin has two reactive thiols located near the C-terminal region
      of its motor domain, the "converter", which rotates by approximately 70 degrees
      upon the transition from the "nucleotide-free" state to the "pre-power stroke"
      state. The incorporation rates of a thiol reagent, 5-(((2
      iodoacetyl)amino)ethyl)aminonaphthalene-1-sulfonic acid (IAEDANS), into these
      thiols were greatly altered by adding ATP or changing the myosin conformation.
      Comparisons of the myosin structures in the pre-power stroke state and the
      nucleotide-free state explained why the reactivity of both thiols is especially
      sensitive to a conformational change around the converter, and thus can be used
      as a sensor of the rotation of the converter. Modeling of the myosin structure in
      the pre-power stroke state, in which the most reactive thiol, "SH1", was
      selectively modified with IAEDANS, revealed that this label becomes an obstacle
      when the converter completely rotates toward its position in the pre-power stroke
      state, thus resulting in incomplete rotation of the converter. Therefore, we
      suggest that the limitation of the converter rotation by modification causes the
      as-yet unexplained phenomena of SH1-modified myosin, including the inhibition of
      10S myosin formation and the losses in phosphorylation-dependent regulation of
      the basic and actin-activated Mg-ATPase activities of myosin.

PMID- 18068119
TI  - A monoclonal antibody (1D12) defines novel distribution patterns of prion protein
      (PrP) as granules in nucleus.
AB  - A monoclonal antibody (mAb) panel to bovine prion protein (PrP) was studied by
      immunoblotting and immunohistochemistry for scrapie and bovine spongiform
      encephalopathy. A mAb panel recognized both normal (PrP(C)) and abnormal
      (PrP(Sc)) isoforms of PrP in murine, ovine and bovine brain tissues.
      Interestingly, an anti-bovine PrP mAb, 1D12, prepared by immunizing PrP gene
      knockout mice with a synthetic polypeptides corresponding to codons 153-166 of
      the bovine PrP gene showed novel patterns of reactivity for prion-uninfected
      neuronal cells. An enzyme-linked immunosorbent assay-mapping of the mAb epitopes
      resulted in a reaction of monoclonal 1D12 to YEDRY and M corresponding to amino
      acids 156-160 and 165 of bovine PrP. Several patterns of bovine PrP(C)
      distribution in PrP-deficient neuronal cells (HpL3-4) transfected with bovine PrP
      were observed after different fixation methods. Stained cell surface was observed
      after formalin fixation by immunofluorescent assay of 1D12 with confocal
      microscopy, whereas granules in nucleus were stained after acetone fixation. No
      reactivity in the nucleus was observed to HpL3-4, or HpL3-4mPrP cells expressing
      mouse PrP. This is the first paper that has reported the detection of the PrP(C)
      at both cell surface and nuclei of prion-uninfected cell line.

PMID- 18068120
TI  - Temperature dependence of the flexural rigidity of single microtubules.
AB  - Although the flexural rigidity of a microtubule has previously been estimated by
      various methods, its temperature dependence has never been systematically
      examined. Here, we measured the flexural rigidity of a single taxol-stabilized
      microtubule from thermal fluctuation of the free end of a microtubule, the other
      end of which was fixed, at different temperatures; the results showed that the
      flexural rigidity is 2.54 x 10(-24)Nm(2) independent of temperature in the range
      of 20-35 degrees C. Next, we applied temperature pulse microscopy (TPM) [K.
      Kawaguchi, S. Ishiwata, Thermal activation of single kinesin molecules with
      temperature pulse microscopy. Cell Motil. Cytoskeleton 49 (2001) 41-47; H. Kato,
      T. Nishizaka, T. Iga, K. Kinosita Jr., S. Ishiwata, Imaging of thermal activation
      of actomyosin motors. Proc. Natl. Acad. Sci. USA 96 (1999) 9602-9606], which
      created the temperature gradient (1-2 degrees C/mum) along a microtubule gliding
      on kinesins in the presence of ATP. As a result, the gliding microtubule was
      buckled between two interacting kinesin molecules, when the microtubule had been
      propelled faster by the rear kinesin (higher temperature) and slower by the front
      one (lower temperature). By estimating the critical force to induce buckling of a
      microtubule, the flexural rigidity of a microtubule was estimated to be (2.7-7.8)
      x 10(-24)Nm(2), which was in good agreement with the value determined above. We
      discuss the buckling process based on the temperature dependence of the force
      velocity relationship of kinesin motility.

PMID- 18068121
TI  - In vitro protein folding by E. coli ribosome: unfolded protein splitting 70S to
      interact with 50S subunit.
AB  - Folding of unfolded protein on Escherichia coli 70S ribosome is accompanied by
      rapid dissociation of the ribosome into 50S and 30S subunits. The dissociation
      rate of 70S ribosome with unfolded protein is much faster than that caused by
      combined effect of translation and polypeptide release factors known to be
      involved in the dissociation of ribosome into subunits. The protein then reaches
      a "folding competent" state on 50S and is released to take up native conformation
      by itself. Release before attaining the folding competent state or prevention of
      release by cross-linking it with ribosome, would not allow the protein to get
      back to its native conformation.

PMID- 18068122
TI  - Novel MHC class I-related molecule MR1 affects MHC class I expression in 293T
      cells.
AB  - Association with beta(2)-microglobulin and binding a ligand are necessary
      conditions for cell surface expression of the antigen presenting molecules. MHC
      class I-related protein, MR1, is suggested to have an antigen presentation
      function, nevertheless the physiological ligand(s) is (are) still to be
      determined. In the present study, by characterising the subcellular deportment of
      human MR1 transfectants, we have shown its differential mobilisation. Our results
      demonstrated a preferential association of MR1 with beta(2)-microglobulin in MHC
      class I-deficient B cell lines. Furthermore, we have evidenced diminished
      expression of classical MHC class I molecules in human MR1-transfected 293T
      cells, showing a possible interaction between MR1 and classical MHC class I
      molecules.

PMID- 18068123
TI  - Nerve growth factor promotes formation of lumen-like structures in vitro through
      inducing apoptosis in human umbilical vein endothelial cells.
AB  - Recent evidence suggests that apoptosis of endothelial cells contributes to lumen
      formation during angiogenesis, but the biological mechanism remains obscure. In
      this study, we investigated the effect of nerve growth factor (NGF), a member of
      the neurotrophin family and a potential angiogenic factor, on human umbilical
      vein endothelial cells (HUVEC) apoptosis and the formation of lumen-like
      structures (LLS) by cultured HUVEC on Matrigel. We demonstrate that NGF induces
      cell apoptosis. NGF treatment has no significant effect on the expression level
      of its two receptors, TrkA and p75NTR. Blockade of both TrkA and p75NTR, but not
      that of either receptor alone significantly decreases NGF-induced cell apoptosis.
      NGF significantly increases formation of LLS which consist substantially of
      apoptotic cells. Application of NGF-neutralizing antibody or simultaneous
      blockade of TrkA and p75NTR significantly blocks spontaneous and NGF-induced LLS
      formation. These data support a role for NGF-induced cell apoptosis in LLS
      formation in vitro.

PMID- 18068124
TI  - Functional significance of octameric RuvA for a branch migration complex from
      Thermus thermophilus.
AB  - The RuvAB complex promotes migration of Holliday junction at the late stage of
      homologous recombination. The RuvA tetramer specifically recognizes Holliday
      junction to form two types of complexes. A single tetramer is bound to the open
      configuration of the junction DNA in complex I, while the octameric RuvA core
      structure sandwiches the same junction in complex II. The hexameric RuvB rings,
      symmetrically bound to both sides of RuvA on Holliday junction, pump out DNA
      duplexes, depending upon ATP hydrolysis. We investigated functional differences
      between the wild-type RuvA from Thermus thermophilus and mutants impaired the
      ability of complex II formation. These mutant RuvA, exclusively forming complex
      I, reduced activities of branch migration and ATP hydrolysis, suggesting that the
      octameric RuvA is essential for efficient branch migration. Together with our
      recent electron microscopic analysis, this finding provides important insights
      into functional roles of complex II in the coordinated branch migration
      mechanism.

PMID- 18068126
TI  - Cardiac marker changes in subjects working at plateau level.

PMID- 18068125
TI  - How are the cellular functions of myosin VI regulated within the cell?
AB  - This review, dedicated to the memory of Professor Setsuro Ebashi, focuses on our
      current work investigating the cellular functions and regulation of the unique
      unconventional motor, myosin VI. This myosin, unlike all the other myosins so far
      studied, moves towards the minus end of actin filaments and has been implicated
      in a wide range of cellular processes such as endocytosis, exocytosis, cell
      migration, cell division and cytokinesis. Myosin VI's involvement in these
      cellular pathways is mediated by its interaction with specific adaptor proteins
      and is regulated by multiple regulatory signals and modifications such as calcium
      ions, PtdIns(4,5)P(2) (PIP(2)) and phosphorylation. Understanding the functions
      of myosin VI within the cell and how it is regulated is now of utmost importance
      given the recent observations that it is associated with a number of human
      disorders such as deafness and cancers.

PMID- 18068127
TI  - Retinoid metabolism and nuclear receptor responses: New insights into coordinated
      regulation of the PPAR-RXR complex.
AB  - Retinoids, naturally-occurring vitamin A derivatives, regulate metabolism by
      activating specific nuclear receptors, including the retinoic acid receptor (RAR)
      and the retinoid X receptor (RXR). RXR, an obligate heterodimeric partner for
      other nuclear receptors, including peroxisome proliferator-activated receptors
      (PPARs), helps coordinate energy balance. Recently, many groups have identified
      new connections between retinoid metabolism and PPAR responses. We found that
      retinaldehyde (Rald), a molecule that can yield RA through the action of
      retinaldehyde dehydrogenases (Raldh), is present in fat in vivo and can inhibit
      PPAR gamma-induced adipogenesis. In vitro, Rald inhibits RXR and PPAR gamma
      activation. Raldh1-deficient mice have increased Rald levels in fat, higher
      metabolic rates and body temperatures, and are protected against diet-induced
      obesity and insulin resistance. Interestingly, one specific asymmetric beta
      carotene cleavage product, apo-14'-carotenal, can also inhibit PPAR gamma and
      PPAR alpha responses. These data highlight how pathways of beta-carotene
      metabolism and specific retinoid metabolites may have direct distinct metabolic
      effects.

PMID- 18068128
TI  - Functional role of Zic2 phosphorylation in transcriptional regulation.
AB  - Zic2 is a transcriptional activator that plays a crucial role in mammalian
      forebrain development. It activates the transcription of target genes by DNA
      binding and recruitment of RNA helicase A (RHA). We recently reported that the
      Zic2-RHA interaction is decreased by phosphatase treatment in vitro. We have now
      identified the phosphorylation site (serine 200) in mouse Zic2. Zic2S200A was
      defective in RHA-binding, and its transcriptional activation ability was
      diminished. These data indicate that Zic2S200 is a target for phosphorylation by
      DNA-dependent protein kinase, regulating Zic2-mediated transcriptional
      activation.

PMID- 18068129
TI  - Parallel increase in p70 kinase activation and tau phosphorylation (S262) with
      Abeta overproduction.
AB  - This study set out to search for a link between overproduction of Abeta and p70S6
      kinase (p70S6K) phosphorylation/activation. Results showed that levels of p
      p70S6K at T421/S424 and T389 are significantly increased in mouse N2a
      neuroblastoma cells carrying human APP with Swedish mutation (APPswe), and in
      transgenic APPswe/PS1 (A246E) mice as compared with respective controls,
      corresponding to the increase of tau phosphorylation at S262. This parallel
      increase in p70S6K activation and tau phosphorylation could be demonstrated by
      treating wild-type N2a cells with Abeta25-35. Our results suggest that the Abeta
      deposition in senile plaques in Alzheimer disease brains might be a primary event
      that activates p70S6K and phosphorylates tau at S262, resulting in microtubule
      disruption.

PMID- 18068130
TI  - Cx23, a connexin with only four extracellular-loop cysteines, forms functional
      gap junction channels and hemichannels.
AB  - Gap junction channels may be comprised of either connexin or pannexin proteins
      (innexins and pannexins). Membrane topologies of both families are similar, but
      sequence similarity is lacking. Recently, connexin-like sequences have been
      identified in mammalian and zebrafish genomes that have only four conserved
      cysteines in the extracellular domains (Cx23), a feature of the pannexins.
      Phylogenetic analyses of the non-canonical "C4" connexins reveal that these
      sequences are indeed connexins. Functional assays reveal that the Cx23 gap
      junctions are capable of sharing neurobiotin, and further, that Cx23 connexins
      form hemichannels in vitro.

PMID- 18068131
TI  - Taxanes, microtubules and chemoresistant breast cancer.
AB  - The taxanes, paclitaxel and docetaxel are microtubule-stabilizing agents that
      function primarily by interfering with spindle microtubule dynamics causing cell
      cycle arrest and apoptosis. However, the mechanisms underlying their action have
      yet to be fully elucidated. These agents have become widely recognized as active
      chemotherapeutic agents in the treatment of metastatic breast cancer and early
      stage breast cancer with benefits gained in terms of overall survival (OS) and
      disease-free survival (DFS). However, even with response to taxane treatment the
      time to progression (TTP) is relatively short, prolonging life for a matter of
      months, with studies showing that patients treated with taxanes eventually
      relapse. This review focuses on chemoresistance to taxane treatment particularly
      in relation to the spindle assembly checkpoint (SAC) and dysfunctional regulation
      of apoptotic signaling. Since spindle microtubules are the primary drug targets
      for taxanes, important SAC proteins such as MAD2, BUBR1, Synuclein-gamma and
      Aurora A have emerged as potentially important predictive markers of taxane
      resistance, as have specific checkpoint proteins such as BRCA1. Moreover,
      overexpression of the drug efflux pump MDR-1/P-gp, altered expression of
      microtubule-associated proteins (MAPs) including tau, stathmin and MAP4 may help
      to identify those patients who are most at risk of recurrence and those patients
      most likely to benefit from taxane treatment.

PMID- 18068132
TI  - Assessment of wound-site redox environment and the significance of Rac2 in
      cutaneous healing.
AB  - We have previously reported that H(2)O(2) is actively generated by cells at the
      wound site and that H(2)O(2)-driven redox signaling supports wound angiogenesis
      and healing. In this study, we have standardized a novel and effective electron
      paramagnetic resonance spectroscopy-based approach to assess the redox
      environment of the dermal wound site in vivo. Rac2 regulates inducible NADPH
      oxidase activation and other functional responses in neutrophils. Using Rac2
      deficient mice we sought to investigate the significance of Rac2 in the wound
      site redox environment and healing responses. Noninvasive measurements of
      metabolism of topically applied nitroxide (15)N-perdeuterated tempone in murine
      excisional dermal wounds demonstrated that the wound site is rich in oxidants,
      the levels of which peak 2 days postwounding in the inflammatory phase. Rac2
      deficient mice had threefold lower production of superoxide compared to controls
      with similar wounds. In these mice, a lower wound-site superoxide level was
      associated with compromised wound closure. Immunostaining of wound edges
      harvested during the inflammatory phase showed that the numbers of phagocytic
      cells recruited to the wound site in Rac2-deficient and control mice were
      similar, but the amount of lipid peroxidation was significantly lower in Rac2
      deficient mice, indicating compromised NADPH oxidase activity. Taken together,
      the findings of this study support that the wound site is rich in oxidants. Rac2
      significantly contributes to oxidant production at the wound site and supports
      the healing process.

PMID- 18068133
TI  - Diazeniumdiolate reactivity in model membrane systems.
AB  - The effect of small unilamellar phospholipid vesicles on the acid-catalyzed
      dissociation of nitric oxide from diazeniumdiolate ions, R(1)R(2)N[N(O)NO](-),
      [1: R(1)=H(2)N(CH(2))(3)-, R(2)=H(2)N(CH(2))(3)NH(CH(2))(4)-; 2:
      R(1)=R(2)=H(2)N(CH(2))(3)-; 3: R(1)=n-butyl-, R(2)=n-butyl-NH2+(CH(2))(6)-; 4:
      R(1)=R(2)=nPr-] has been examined at pH 7.4 and 37 degrees C. NO release was
      catalyzed by anionic liposomes (DPPG, DOPG, DMPS, POPS and DOPA) and by mixed
      phosphatidylglycerol/phosphatidylcholine (DPPG/DPPC and DOPG/DPPC) covesicles,
      while cationic liposomes derived from 1,2-dioleoyl-3-trimethylammonium-propane
      (DOTAP) and the zwitterionic liposome DMPC did not significantly affect the
      dissociation rates of the substrates examined. Enhancement of the dissociation
      rate constant in DPPG liposome media (0.010M phosphate buffer, pH 7.4, 37 degrees
      C) at 10mM phosphoglycerol levels, ranged from 37 for 1 to 1.2 for the anionic
      diazeniumdiolate 4, while DOPA effected the greatest rate enhancement, achieving
      49-fold rate increases with 1 under similar conditions. The observed catalysis
      decreases with increase in the bulk concentration of electrolytes in the reaction
      media. Quantitative analysis of catalytic effects has been obtained through the
      application of pseudo-phase kinetic models and equilibrium binding constants at
      different liposome interfaces are compared. The stoichiometry of nitric oxide
      release from 1 and 2 in DPPG/DPPC liposome media has been obtained through
      oxyhemoglobin assay. DPPG=1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1
      glycerol)], DOPG=1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)], DMPS=1,2
      dimyristoyl-sn-glycero-3-[phospho-l-serine], POPS=1-palmitoyl-2-oleoyl-sn-glycero
      3-[phospho-l-serine], DOPA=1,2-dioleoyl-sn-glycero-3-phosphate; DPPC=1,2
      dipalmitoyl-sn-glycero-3-phosphocholine, DMPC=1,2-dimyristoyl-sn-glycero-3
      phosphocholine, DOTAP=1,2-dioleoyl-3-trimethylammonium-propane.

PMID- 18068134
TI  - Protein synthesis inhibitors enhance the expression of mRNAs for early inducible
      inflammatory genes via mRNA stabilization.
AB  - Expression of inflammatory genes is regulated at multiple steps, including
      transcriptional activation and mRNA stabilization. During an investigation into
      the requirement of de novo protein synthesis for the induction of inflammatory
      genes, it was revealed that protein synthesis inhibitors unexpectedly potentiated
      the induction of mRNAs for primary response genes, while the inhibitors
      suppressed the induction of secondary inducible genes as previously described.
      Stimulus-induced nuclear translocation and promoter recruitment of NF-kappaB,
      which is responsible for the transcriptional activation of many inflammatory
      genes, were largely unaffected by the inhibitors. Instead, these inhibitors
      prolonged the half-lives of all of the primary inducible mRNAs tested. Thus,
      these findings emphasize the important contribution of regulated mRNA longevity
      to gene expression induced by pro-inflammatory stimulation.

PMID- 18068135
TI  - Promoter analysis of the mouse Peg3 gene.
AB  - Mouse Peg3 is a paternally expressed gene. Study of methylation of the Peg3 gene
      in P19 embryonal carcinoma cells suggested that monoallelic methylation of CpG
      dinucleotides is not only present in the promoter region, but also in the first
      exon and the first intron. Promoter activity analysis demonstrated that the
      minimal promoter of the Peg3 gene is located in the region between -827 and +712
      and the critical region for promoter activity is between +423 and +712. We
      further identified the roles of the cis-elements, conserved sequence element
      (CSE) and YY1-binding sites, in the regulation of Peg3 expression and found that
      CSE is involved in the inhibition of Peg3 expression, while YY1-binding sites
      serve as activating cis-elements to antagonize CSE-mediated inhibition.

PMID- 18068136
TI  - Abandoning small-scale fish farming in western Kenya leads to higher malaria
      vector abundance.
AB  - Fishponds become abandoned due to lack of access to both young fish and technical
      support and faster economic returns from other activities. Certain conditions
      found in abandoned fishponds, such as absence of fish and presence of aquatic
      vegetation, are conducive to the presence of malaria vectors. We conducted a
      district-wide fishpond census to determine the maintenance status and mosquito
      populations of fishponds in Kisii Central District in western Kenya. Two hundred
      and sixty one fishponds were found, 186 active (fish present) and 75 abandoned
      (fish absent). Vegetation was not significantly associated with the distribution
      of Anopheles gambiae s.l., Anopheles funestus or culicines (Diptera: Culicidae)
      in active or abandoned ponds. The presence of fish, however, correlated
      significantly with the distribution of all mosquito species, with significantly
      higher mosquito densities in abandoned fishponds. An. gambiae s.l. was the most
      abundant mosquito species found in both active and abandoned ponds, being
      proportionally more abundant in the abandoned ponds. The proportion of An.
      funestus increased with altitude. Following the census the demand for fish to re
      stock abandoned ponds rose by 67% when compared to the same time period in the
      previous year. This study highlights the potential public health problems
      associated with the abandonment of small-scale fish farming in the highlands of
      western Kenya.

PMID- 18068137
TI  - Genetic association of preeclampsia to the inflammatory response gene SEPS1.
AB  - OBJECTIVE: The objective of the study was to test for a genetic association
      between the G-105A promoter polymorphism of the inflammatory mediator
      Selenoprotein S (SEPS1) and preeclampsia. STUDY DESIGN: A retrospective study in
      a large Norwegian case-control cohort compared maternal genotype and allele
      frequencies of the SEPS1 g.-105G>A polymorphism genotyped by SNPlex assay in
      preeclamptic (n = 1139) and control (n = 2269) women. Statistical significance
      was determined by chi2 and multivariate regression analyses. RESULTS: Women with
      preeclampsia were 1.34 times more likely to have the GA or AA genotype (P =
      .0039; 95% confidence interval [CI] 1.09 to 1.64) and 1.22 times more likely to
      carry the A allele (P = .023; odds ratio, 1.22; 95% CI, 1.02 to 1.46).
      CONCLUSION: The A allele of the SEPS1-105G>A polymorphism is a significant risk
      factor for preeclampsia in this population.

PMID- 18068138
TI  - Body mass index and weight gain prior to pregnancy and risk of gestational
      diabetes mellitus.
AB  - OBJECTIVE: The objective of the study was to evaluate obesity and rate of weight
      change during the 5 years before pregnancy and risk of gestational diabetes
      mellitus (GDM) in a nested case-control study. STUDY DESIGN: GDM cases (n = 251)
      and controls (n = 204) were selected from a multiethnic cohort of 14,235 women
      who delivered a live birth between 1996 and 1998. Women who gained or lost weight
      were compared with those with a stable weight (+/- 1.0 kg/year). RESULTS: Women
      who gained weight at a rate of 1.1 to 2.2 kg/year had a small increased risk of
      GDM (odds ratio [OR] 1.63 [95% confidence interval (CI) 0.95 to 2.81]) and women
      who gained weight at a rate of 2.3 to 10.0 kg/year had a 2.5-fold increased risk
      of GDM (OR 2.61 [95% CI, 1.50 to 4.57]), compared with women with stable weight
      (after adjusting for age, race-ethnicity, parity, and baseline body mass index).
      CONCLUSION: Weight gain in the 5 years before pregnancy may increase the risk of
      GDM.

PMID- 18068139
TI  - Circulating endothelial cells: a marker of vascular damage in patients with
      preeclampsia.
AB  - OBJECTIVE: Preeclampsia is a disorder of endothelial cells, and novel markers of
      the disease are eagerly awaited. We tested the hypothesis that circulating
      endothelial cells (CECs) are elevated in preeclampsia and that cell numbers
      correlate with disease activity. STUDY DESIGN: CECs were measured in 10 patients
      with preeclampsia as well as pregnant and nonpregnant controls. Cells were
      enumerated prior to delivery, 1 and 3-5 days thereafter. Enumeration of CECs was
      performed with anti-CD 146-driven immunomagnetic isolation and subsequent Ulex
      lectin staining. RESULTS: Markedly elevated CEC numbers were detected in women
      with preeclampsia (median 88 cells/mL; P < .001) when compared with normal
      pregnancies (median 16 cells/mL) and healthy nonpregnant women (12 cells/mL).
      There was a significant correlation of CEC numbers and systolic blood pressure (P
      < .02). A rapid decline of cell numbers after delivery paralleled the clinical
      recovery. CONCLUSION: Circulating endothelial cells are a novel marker of
      vascular damage in preeclampsia.

PMID- 18068140
TI  - Antepartum uterine contraction patterns in twin pregnancies with and without
      preterm labor and delivering before or after 36 weeks.
AB  - OBJECTIVE: The purpose of this study was to identify differences in antepartum
      uterine contraction frequency (UCF) in twin pregnancies with and without preterm
      labor (PTL). STUDY DESIGN: Twin gestations enrolled for outpatient surveillance
      with twice daily electronic uterine activity monitoring and telephonic nursing
      assessment, without interventional delivery were identified. Mean UCF for each
      gestational week was compared between women without PTL or preterm delivery (PTD)
      < 36 weeks (controls) and those with a PTL diagnosis delivering at < 36 weeks
      (PTL/PTD group), and those with PTL with delivery > or = 36 weeks (PTL/GAD > or =
      36 group). RESULTS: Data from 7891 patients with 267,840 monitored hours were
      analyzed. UCF at each gestational week was significantly higher for patients
      experiencing PTL with or without PTD compared to control. UCF was similar for
      patients with PTL with or without PTD < 36. CONCLUSION: Twin pregnancies
      complicated with PTL have a higher UCF than those that do not experience PTL.
      Outpatient surveillance may be beneficial in this population.

PMID- 18068141
TI  - Anaphylactoid syndrome of pregnancy immediately after intrauterine pressure
      catheter placement.
AB  - A 35-year-old multipara woman underwent intrauterine pressure catheter placement
      during labor. Immediately afterwards, she had severe dyspnea develop, became
      unresponsive, and had a prolonged fetal bradycardia. During emergency cesarean
      section, she required cardiopulmonary resuscitation repetitively. She then had
      disseminated intravascular coagulopathy develop and underwent hysterectomy.
      Anaphylactic reaction may be associated with intrauterine pressure catheter
      placement.

PMID- 18068142
TI  - Hematogenous infection of Sprague-Dawley rats with Mycoplasma pulmonis:
      development of a model for maternal and fetal infection.
AB  - OBJECTIVES: The specific objective of this study was to conduct a dose response
      experiment with Mycoplasma pulmonis in Sprague-Dawley rats to develop a
      reproducible animal model of maternal and fetal infection that would provide a
      versatile mechanism to address the innate fetal immune response during
      intrauterine infection. STUDY DESIGN: Pregnant rats were infected intravenously
      at gestation day 14 with 0 (control), 10(1), 10(3), 10(5), and 10(7) colony
      forming units of M. pulmonis and necropsied at gestational day 18. Quantitative
      culture of maternal and fetal tissues as well as histopathologic examination of
      the placenta were performed. RESULTS: We have characterized a rat model of
      maternal and fetal infection that can be manipulated by alteration of infectious
      dose. Colonization of Sprague-Dawley rat dam and fetal tissues by M. pulmonis
      occurred in a dose-dependent manner after intravenous inoculation (P < .001).
      Placental lesion severity increased with infection dose (P = .0001). The minimum
      threshold dose required to establish infection of the dam and fetus was at least
      10(3) colony forming units, with consistent colonization of maternal and fetal
      tissues achieved only with 10(7) colony forming units. In some instances, rat
      fetal tissues could be colonized in the absence of concomitant amniotic fluid
      colonization. Interestingly, there appeared to be a predilection for colonization
      of the reproductive tissues. CONCLUSIONS: In the Sprague-Dawley rat, the
      infection rate of both the dam and fetus can be controlled by the inoculum dose.
      Our data support the concept that hematogenous spread of M. pulmonis to the rat
      fetus can occur without amniotic fluid infection and suggest that the fetus
      itself can potentially seed the amniotic fluid with microorganisms. Importantly,
      manipulation of both the route of infection as well as infection dose provide a
      reproducible way to study both maternal and fetal immune response to infection
      during pregnancy.

PMID- 18068143
TI  - Radiofrequency driven cord occlusion for selective termination of pregnancy:
      evaluation in the fetal sheep.
AB  - OBJECTIVE: This study was designed to assess the ability of an ultrasound-guided
      radiofrequency (RF)-driven procedure to induce complete and irreversible cord
      occlusion using a 90 days fetal sheep model. STUDY DESIGN: Twenty 90 days
      gestation sheep underwent general anesthesia. The first ten fetuses were exposed
      under hysterotomy, and RF electrode was inserted visually in the middle of the
      umbilical cord and deployed. Fetuses were then replaced into the amniotic fluid
      and RF procedure (average target temperature of 100 degrees C during 10 minutes)
      was applied. For the next ten fetuses, RF electrode was inserted into the cords
      under trans-parietal ultrasound guidance and the same RF procedure was applied.
      Cord occlusion was assessed by Doppler examination (absence of cordonal flows at
      the end of the procedure and until fetal heart failure occurred) and by
      subsequent histopathological analysis. RESULTS: Cord occlusion was always
      complete at Doppler examination at the end of RF procedure for the ten
      experiments realized under hysterotomy. No cordonal reperfusion was observed
      until fetal heart failure. Histopathological analysis confirmed cordonal
      occlusion at the site of impact. Neither cordonal rupture nor cordonal bleeding
      was observed for any of the ten experiments. When RF electrode was inserted under
      ultrasound guidance, complete occlusion could be obtained only for 6 of the ten
      experiments. CONCLUSION: Our results suggest that RF might be an appropriate
      method for selective termination of pregnancy. Yet, optimal insertion of the
      electrode is required to engender a complete and irreversible cord occlusion, and
      ultrasound-guidance training seems necessary before current human application.

PMID- 18068144
TI  - Laser therapy and serial amnioreduction as treatment for twin-twin transfusion
      syndrome: a metaanalysis and review of literature.
AB  - OBJECTIVE: The objective of the study was to review current controversy on laser
      therapy (LT) vs serial amnioreduction (SA) performed for twin-twin transfusion
      syndrome (TTTS). STUDY DESIGN: A search in PubMed from 1997-2007 was performed.
      Inclusion criteria were diamniotic monochorionic pregnancy, TTTS diagnosed with
      standard parameters, and peri- and neonatal outcomes well defined. Triplets and
      investigations on other topics of TTTS rather than perinatal outcomes were
      excluded. A metaanalysis was performed by fixed-effect model (heterogeneity
      <25%). RESULTS: Ten articles provided 611 cases of TTTS (LT: 70%; SA: 30%) and
      included 4 studies comparing the 2 treatments (395 cases: LT, 58%; SA, 42%).
      Fetuses undergoing LT were more likely to survive than fetuses undergoing SA
      (overall survival rate: P < .0001; odds ratio [OR], 2.04; 95% confidence interval
      [CI], 1.52-2.76; neonatal death: P < .0001; OR, 0.24; 95% CI, 0.15-0.40;
      neurologic morbidity: P < .0001; OR, 0.20; 95% CI, 0.12-0.33). CONCLUSION: This
      metaanalysis shows that LT is associated with better outcomes than SA and
      proposes new topics for future research.

PMID- 18068145
TI  - Intraabdominal pressure changes associated with lifting: implications for
      postoperative activity restrictions.
AB  - OBJECTIVE: The purpose of this study was to describe the effect of the lifting
      maneuver and the quantity of weight lifted on the generation of intraabdominal
      pressure. STUDY DESIGN: Forty-one women who underwent urodynamic evaluation
      performed 4 lifting maneuvers, each while lifting 0, 2.5, 5, 10, and 15 kg. The
      lifting maneuvers were routine activities that included squatting with and
      without assistance, lifting from a counter, and receiving weight. Pressure was
      recorded with a rectal microtip catheter. Each lift was performed twice, and the
      average pressure change was analyzed. RESULTS: When controlled for potential
      confounding variables, repeated-measures analysis of variance revealed a
      significant interaction between lift weight and lift maneuver (P < .001).
      Squatting was associated with generation of higher intraabdominal pressure than
      lifting from a counter or receiving weights into outstretched arms (P < .001).
      Lifting > or = 2.5 kg resulted in significant changes in intraabdominal pressure,
      regardless of lift maneuver (P < .001). CONCLUSION: Both the lifting maneuver and
      the quantity of weight should be considered when counseling patients regarding
      postoperative lifting.

PMID- 18068146
TI  - Itraconazole vs fluconazole for the treatment of uncomplicated acute vaginal and
      vulvovaginal candidiasis in nonpregnant women: a metaanalysis of randomized
      controlled trials.
AB  - In this metaanalysis of randomized controlled trials (RCTs) we aimed to compare
      the in vivo and in vitro activity and the safety of per os itraconazole and
      fluconazole treatment of uncomplicated acute vaginal/vulvovaginal candidiasis in
      nonpregnant women. We used PubMed, Scopus, Web of Science, and Cochrane Library
      to identify the studies that were relevant to our metaanalysis RCTs. Six RCTs
      were included in this study that comprised 1092 enrolled patients with signs and
      symptoms of vaginal/vulvovaginal candidiasis that was confirmed by microscopy
      and/or microbiologic cultures that were obtained from the ectocervix and/or
      vaginal fundus. Overall, there was no difference between itraconazole and
      fluconazole regarding clinical cure and improvement at the first and second
      scheduled visit assessments (pooled odds ratio [OR], 0.94 [95% CI, 0.6-1.48] and
      1.09 [95% CI, 0.68-1.75], respectively), mycologic cure at the first and second
      scheduled visit assessments (OR, 0.73 [95% CI, 0.31-1.7] and 0.71 [95% CI, 0.49
      1.03], respectively), withdrawal of patients because of severe adverse events
      (OR, 0.72 [95% CI, 0.16-3.32]), and adverse events noted from the nervous and
      digestive systems (OR, 1.07 [95% CI, 0.42-2.73] and 1.84 [95% CI, 0.3-11.27],
      respectively). In conclusion, effectiveness and safety of oral itraconazole and
      fluconazole in the treatment of acute uncomplicated vaginal/vulvovaginal
      candidiasis are similar.

PMID- 18068147
TI  - An immunohistochemical and ultrastructural study of the pericellular matrix of
      uneroded hypertrophic chondrocytes in the mandibular condyle of aged c-src
      deficient mice.
AB  - OBJECTIVE: Previous studies indicate that hypertrophic chondrocytes can
      transdifferentiate or dedifferentiate and redifferentiate into bone cells during
      the endochondral bone formation. Mandibular condyle in aged c-src-deficient mice
      has incremental line-like striations consisting of cartilaginous and non
      cartilaginous layers, and the former contains intact hypertrophic chondrocytes in
      uneroded lacunae. The purpose of this study is to determine the phenotype changes
      of uneroded hypertrophic chondrocytes. DESIGN: Immunohistochemical and
      ultrastructural examinations of the pericellular matrix of hypertrophic
      chondrocytes in the upper, middle, and lower regions of the mandibular condyle
      were conducted in aged c-src-deficient mice, using several antibodies of
      cartilage/bone marker proteins. RESULTS: Co-localisation of aggrecan, type I
      collagen, and dentin matrix protein-1 (DMP-1) or matrix extracellular
      phosphoprotein (MEPE) was detected in the pericellular matrix of the middle
      region. Ultrastructurally, granular substances in the pericellular matrix of the
      middle region were the remains of upper region chondrocytes, which were mixed
      with thick collagen fibrils. In the lower region, the width of the pericellular
      matrix and the amount of collagen fibrils were increased. Versican, type I
      collagen, DMP-1, and MEPE were detected in the osteocyte lacunae. Additionally,
      DMP-1 and MEPE were detected in the pericellular matrix of uneroded hypertrophic
      chondrocytes located in the lower, peripheral region of the mandibular condyle in
      younger c-src-deficient mice, but not in the aged wild-type mice. CONCLUSIONS:
      These results indicate that long-term survived, uneroded hypertrophic
      chondrocytes, at least in a part, acquire osteocytic characteristics.

PMID- 18068148
TI  - Melittin exhibits necrotic cytotoxicity in gastrointestinal cells which is
      attenuated by cholesterol.
AB  - Melittin, a cationic antimicrobial peptide isolated from the venom of Apis
      mellifera, has shown potential as a permeability enhancer, transiently increasing
      intestinal permeability and enhancing the absorption of paracellular markers.
      Although it is cytotoxic to eukaryotic cells, its cytotoxicity is significantly
      lower in polarised epithelia compared to non-polarised cells. The aim of this
      study was to explore the mechanism of melittin cytotoxicity in gastrointestinal
      cells and to determine whether cytotoxicity was mediated by a necrotic or an
      apoptotic pathway. The role of cholesterol in melittin cytotoxicity was also
      examined. Using four distinct assays for apoptosis, phosphatidylserine
      translocation, caspase activation, DNA ladder formation and cell cycle analysis,
      no evidence of apoptotic pathway for cell death was observed with any of these
      approaches. It can therefore be concluded that cytotoxicity was likely to be
      mediated by necrosis in gastrointestinal epithelial cells. However, at low
      concentrations of melittin (<1 microM), BRDU uptake was enhanced, demonstrating
      proliferative effects of melittin at sub-lethal concentrations. Furthermore,
      melittin cytotoxicity was further enhanced by depletion of cholesterol, using
      methyl-beta-cyclodextrin, indicating that cholesterol depleting agents could be
      contradictory to its potential as an enhancer. Overall, although melittin appears
      to stimulate necrosis, with careful dosage selection the peptide could be
      considered for the oral delivery of poorly bioavailable drugs.

PMID- 18068149
TI  - A novel gender-related difference in the constitutive expression of hepatic
      cytochrome P4501A subfamily enzymes in Meishan pigs.
AB  - Constitutive expression levels of hepatic CYP1A subfamily enzymes, CYP1A1 and
      CYP1A2, in male and female Meishan pigs were examined at levels of the mRNA,
      protein, and enzyme activity. In mature (5-month-old) pigs, levels of hepatic
      CYP1A1 and CYP1A2 mRNAs, as determined by RT-PCR, were much higher in females
      than in males, but those of castrated male pigs were equivalent to female pigs.
      The gender-related differences in the levels of CYP1A mRNAs closely correlated
      with those of the corresponding apoproteins determined by Western blotting.
      Hepatic enzyme activities not only for the O-dealkylation of ethoxyresorufin and
      methoxyresorufin (typical substrates for CYP1A1 and CYP1A2, respectively) but
      also for the mutagenic activation of benzo[a]pyrene and 2-amino-6-methyl
      dipyrido[1,2-a; 3',2'-d]imidazole (typical substrates for CYP1A1 and CYP1A2,
      respectively) were also much greater in female and castrated male pigs than in
      male pigs. In immature (1-month-old) pigs, no such gender-related differences
      were observed, and their gene expression levels of the CYP1A subfamily enzymes
      were almost the same as those of mature female pigs. Furthermore, treatment of
      immature pigs with testosterone resulted in a drastic decrease in the levels of
      the CYP1A1 and CYP1A2 mRNAs in both sexes. The present findings demonstrate a
      gender-related difference in the constitutive expression of hepatic CYP1A
      subfamily enzymes in Meishan pigs and further indicate that androgen down
      regulates the constitutive gene expression of the enzymes.

PMID- 18068150
TI  - Affective picture perception: emotion, context, and the late positive potential.
AB  - Event-related potentials (ERP) were measured when pleasant, neutral or unpleasant
      pictures were presented in the context of similarly valenced stimuli, and
      compared to ERPs elicited when the same pictures were viewed in an intermixed
      context. An early ERP component (150-300 ms) measured over occipital and fronto
      central sensors was specific to viewing pleasant pictures and was not affected by
      presentation context. Replicating previous studies, emotional pictures prompted a
      larger late positive potential (LPP, 400-700 ms) and a larger positive slow wave
      (1-6 s) over centro-parietal sensors that also did not differ by presentation
      context. On the other hand, ERPs elicited when viewing neutral pictures varied as
      a function of context, eliciting somewhat larger LPPs when presented in blocks,
      and prompting smaller slow waves over occipital sensors. Taken together, the data
      indicate that emotional pictures prompt increased attention and orienting that is
      unaffected by its context of presentation, whereas neutral pictures are more
      vulnerable to context manipulations.

PMID- 18068151
TI  - Biases towards internal features in infants' reasoning about objects.
AB  - This paper reports the results of two sets of studies demonstrating 14-month
      olds' tendency to associate an object's behavior with internal, rather than
      external features. In Experiment 1 infants were familiarized to two animated cats
      that each exhibited a different style of self-generated motion. Infants then saw
      a novel individual that had an internal feature (stomach color) similar to one
      cat, but an external feature (hat color) similar to the other. Infants looked
      reliably longer when the individual's motion was congruent with the hat than when
      it was congruent with the stomach. Using a converging method involving object
      choice, Experiment 2 found that infants prioritized the internal feature over the
      external feature only when the object's behavior was self-generated. In the
      absence of self-generated behaviors, however, infants did not show a preference
      towards the internal feature.

PMID- 18068152
TI  - Nemo is required in a subset of photoreceptors to regulate the speed of
      ommatidial rotation.
AB  - Both dramatic and subtle morphogenetic movements are of paramount importance in
      molding cells and tissues into functional form. Cells move either independently
      or as populations and the distance traversed by cells varies greatly, but in all
      cases, the output is common: to organize cells into or within organs and
      epithelia. In the developing Drosophila eye, a highly specialized, 90 degrees
      rotational movement of subsets of cells imposes order by polarizing the retinal
      epithelium across its dorsoventral axis. This process was proposed to take place
      in two 45 degrees steps, with the second under control of the gene nemo (nmo), a
      serine/threonine kinase. While our analysis confirms that these subsets of cells,
      the ommatidial precursors, do stall at 45 degrees , we demonstrate that nmo is
      also required through most of the first 45 degrees of rotation to regulate the
      speed at which the ommatidial precursors move. In addition, although the
      precursors reach only the halfway point by the end of larval life, this work
      demonstrates that patterning events that occur during pupal life move the
      ommatidial units an additional 15 degrees . A re-analysis of nmo mosaic clones
      indicates that nmo is required in photoreceptors R1, R6 and R7 for normal
      orientation. This work also demonstrates that two major isoforms of nmo rescue
      the nmo(P1) phenotype. Finally, a dominant modifier screen of a nmo misexpression
      background identified genomic regions that potentially regulate rotation. The
      results presented here suggest a model in which a motor for rotation is
      established in a nemo-dependent fashion in a subset of cells.

PMID- 18068153
TI  - Diet controls normal and tumorous germline stem cells via insulin-dependent and 
      independent mechanisms in Drosophila.
AB  - The external environment influences stem cells, but this process is poorly
      understood. Our previous work showed that germline stem cells (GSCs) respond to
      diet via neural insulin-like peptides (DILPs) that act directly on the germ line
      to upregulate stem cell division and cyst growth under a protein-rich diet in
      Drosophila. Here, we report that DILPs specifically control the G2 phase of the
      GSC cell cycle via phosphoinositide-3 kinase (PI3K) and dFOXO, and that a
      separate diet mediator regulates the G1 phase. Furthermore, GSC tumors, which
      escape the normal stem cell regulatory microenvironment, or niche, still respond
      to diet via both mechanisms, indicating that niche signals are not required for
      GSCs to sense or respond to diet. Our results document the effects of diet and
      insulin-like signals on the cell cycle of stem cells within an intact organism
      and demonstrate that the response to diet requires multiple signals. Moreover,
      the retained ability of GSC tumors to respond to diet parallels the long known
      connections between diet, insulin signaling, and cancer risk in humans.

PMID- 18068155
TI  - Fucoidan partly prevents CCl4-induced liver fibrosis.
AB  - Fucoidan, a sulfated polysaccharide extracted from brown algae, has a wide range
      of biological activities, including anti-inflammatory, anti-viral, and anti-tumor
      activities. In the present study, we investigated the effects of fucoidan on CCl4
      induced liver fibrosis. Administration of fucoidan reduced CCl4-induced acute and
      chronic liver failure. Hepatic fibrosis induced by CCl4 was also attenuated by
      injection of fucoidan. Damage to hepatocytes and activation of hepatic stellate
      cells are key events in liver fibrosis, and, interestingly, treatment of
      hepatocytes with fucoidan prevented CCl4-induced cell death and inhibited the
      proliferation hepatic stellate cells. These results indicate that fucoidan might
      be a promising anti-fibrotic agent possessing dual functions, namely, protection
      of hepatocytes and inhibition of hepatic stellate cell proliferation.

PMID- 18068154
TI  - Evaluation of [3-(1-methyl-1H-indol-3-yl-methylene)-2-oxo-2, 3-dihydro-1H-indole
      5-sulfonamide] (OXSI-2), as a Syk-selective inhibitor in platelets.
AB  - In the present study, we characterized OXSI-2 [3-(1-Methyl-1H-indol-3-yl
      methylene)-2-oxo-2, 3-dihydro-1H-indole-5-sulfonamide], a putative inhibitor of
      Syk, and determined its specificity and selectivity in platelets. We found that
      OXSI-2 completely abolished convulxin-induced platelet functional responses. In
      order to determine whether OXSI-2 inhibited Src family kinase-mediated platelet
      responses, we evaluated its effect on Src family kinase (SFK)-mediated signaling
      events in platelets, viz. Lyn-mediated phosphorylation of Y352 on Syk, LAT-Y191
      phosphorylation by Syk, and protease-activated receptor (PAR)-mediated
      phosphorylation of ERK. In the present work, we report that convulxin mediated
      Syk tyrosine 352 phosphorylation is not inhibited by OXSI-2, whereas piceatannol
      and PP2 abolished it. Syk-mediated Y191 LAT phosphorylation is abolished by all
      the three inhibitors. AYPGKF-induced phosphorylation of ERK was marginally
      inhibited by OXSI-2, whereas treatment with PP2 and piceatannol completely
      abolished it. However, PAR-mediated thromboxane generation (an event mediated by
      ERK) was potentiated by OXSI-2 whereas PP2 and piceatannol brought thromboxane to
      basal levels. Protein kinase C (PKC) inhibitors are known to potentiate PAR
      mediated thromboxane generation in platelets. In contrast, OXSI-2, unlike PKC
      inhibitors, did not inhibit secretion. Therefore, we conclude that OXSI-2 is not
      a Syk-selective inhibitor in platelets because of its unexplained non-specific
      effects.

PMID- 18068157
TI  - Prevalence of Cryptosporidium and Giardia species in animals in irrigation
      catchments in the southwest of Australia.
AB  - Screening of 445 animal faecal samples in irrigation catchments in Western
      Australia (WA) was conducted to identify the prevalence of Cryptosporidium and
      Giardia species. Of the samples positive for Giardia duodenalis, 30.7% (12/36)
      were the zoonotic Assemblage A, while approximately 13% (4/30) of Cryptosporidium
      positives were zoonotic. This is the first finding of Giardia Assemblage A in
      native marsupials and birds and indicates that marsupials and possibly birds may
      potentially be a reservoir of zoonotic Giardia.

PMID- 18068156
TI  - DNA polymerase eta reduces the gamma-H2AX response to psoralen interstrand
      crosslinks in human cells.
AB  - DNA interstrand crosslinks are processed by multiple mechanisms whose
      relationships to each other are unclear. Xeroderma pigmentosum-variant (XP-V)
      cells lacking DNA polymerase eta are sensitive to psoralen photoadducts created
      under conditions favoring crosslink formation, suggesting a role for translesion
      synthesis in crosslink repair. Because crosslinks can lead to double-strand
      breaks, we monitored phosphorylated H2AX (gamma-H2AX), which is typically
      generated near double-strand breaks but also in response to single-stranded DNA,
      following psoralen photoadduct formation in XP-V fibroblasts to assess whether
      polymerase eta is involved in processing crosslinks. In contrast to conditions
      favoring monoadducts, conditions favoring psoralen crosslinks induced gamma-H2AX
      levels in both XP-V and nucleotide excision repair-deficient XP-A cells relative
      to control repair-proficient cells; ectopic expression of polymerase eta in XP-V
      cells normalized the gamma-H2AX response. In response to psoralen crosslinking,
      gamma-H2AX as well as 53BP1 formed coincident foci that were more numerous and
      intense in XP-V and XP-A cells than in controls. Psoralen photoadducts induced
      gamma-H2AX throughout the cell cycle in XP-V cells. These results indicate that
      polymerase eta is important in responding to psoralen crosslinks, and are
      consistent with a model in which nucleotide excision repair and polymerase eta
      are involved in processing crosslinks and avoiding gamma-H2AX associated with
      double-strand breaks and single-stranded DNA in human cells.

PMID- 18068158
TI  - Roles of Dickkopf-1 and its receptor Kremen1 during embryonic implantation in
      mice.
AB  - OBJECTIVE: To determine the roles of Dickkopf-1 (Dkk1) in mouse embryo
      implantation. DESIGN: Experimental prospective study. SETTING: Animal research
      and institute laboratory facility. PATIENT(S): Virgin Kunming female mice and
      adult male mice. INTERVENTION(S): The expression of Dkk1 and its receptor Kremen1
      in embryos and uteri was observed by immunofluorescence or immunohistochemistry.
      Then, Dkk1 or Kremen1 antisense oligodeoxynucleotides (ODNs) were used to assess
      their effects on embryo implantation in in vitro or in vivo assays. MAIN OUTCOME
      MEASURE(S): Dynamic changes of Dkk1 and Kremen1 in embryos and uterine stroma
      during the window of implantation. RESULT(S): Dickkopf-1 and Kremen1 are
      expressed dynamically in both embryos and uterine stroma during embryonic
      implantation. Dickkopf-1 or Kremen1 antisense ODNs significantly inhibited the
      adhesion and outgrowth of hatched blastocysts on fibronectin. The expressional
      patterns of Dkk1 and Kremen1 proteins in the uterine stroma of pseudopregnant,
      implantation-delayed, and artificially decidualized mice imply the roles of these
      proteins in uterine receptivity and decidualization. Time-dependent increases of
      Dkk1 and Kremen1 in uterine stromal cells of ovariectomized mice treated with
      steroids further suggest that their expression was under the control of maternal
      steroids E(2) and P. Embryo implantation also was inhibited when Dkk1 antisense
      ODNs were injected into mouse uterine horns on day 3 of pregnancy. CONCLUSION(S):
      These results suggest an important role of Dkk1 and Kremen1 in blastocyst
      activation and uterine receptivity during the window of implantation.

PMID- 18068159
TI  - Vasomotor symptoms in infertile premenopausal women: a hitherto unappreciated
      risk for low bone mineral density.
AB  - OBJECTIVE: To identify the prevalence of vasomotor symptoms (VMS) in a population
      of premenopausal infertile women and to determine whether VMS is associated with
      enhanced bone turnover and low bone mineral density (BMD). DESIGN: Cross
      sectional study. SETTING: Academic infertility practice. PATIENT(S): Eighty-two
      premenopausal infertile, but otherwise healthy, women attending for routine
      infertility care. INTERVENTION(S): Bone mineral density testing, general health
      and Profile of Mood States questionnaires, and serum samples (cycle d 1-3). MAIN
      OUTCOME MEASURE(S): Vasomotor symptoms, specifically hot flashes (HF) and night
      sweats (NS); BMD z score, BMD categorized as low (Z <or= -1.0) or normal (Z > 
      1.0); ovarian reserve assessment (biochemical and ovarian dimensions on
      transvaginal ultrasound); and serum markers of bone turnover (collagen N-terminal
      telo-peptide, tartrate-resistant acid phosphatase, and bone-specific alkaline
      phosphatase) and ovarian reserve (FSH, E(2), and inhibin B). Multivariable
      regression analyses determined the associations between VMS, BMD, and bone
      turnover (individual markers and composite turnover score). RESULT(S): The
      prevalence of VMS was 12% in this relatively young population (mean [+/- SD] age
      [years], 34.53 +/- 4.32). Symptomatic women were statistically significantly more
      likely to report sleep disturbances and to exhibit evidence of low BMD, as well
      as to exhibit enhanced bone turnover and poorer ovarian reserve parameters.
      Multivariable logistic regression analyses confirmed the statistical significance
      of both HF and NS as independent correlates to low BMD after adjusting for age,
      body mass index, smoking status, menstrual regularity, and ovarian reserve
      status. Multivariable linear regression analyses demonstrated that NS, but not
      HF, predicted higher bone turnover at a statistically significant level after
      adjusting for age, smoking, menstrual regularity, and ovarian reserve.
      CONCLUSION(S): We demonstrate, in a premenopausal population of infertile women,
      evidence of morbid accompaniments to VMS, including sleep disturbances and
      evidence of low BMD. Our data further suggest a state of enhanced bone turnover
      in association with VMS, specifically in those experiencing NS. Declining ovarian
      reserve may be the common pathophysiological mechanism underlying VMS and low BMD
      in the symptomatic population and merits further investigation.

PMID- 18068160
TI  - Is overweight a risk factor for reduced semen quality and altered serum sex
      hormone profile?
AB  - OBJECTIVE: To evaluate whether overweight and obesity are related to changes in
      serum sex hormone concentrations and semen quality. DESIGN: Cross-sectional
      study. SETTING: Data from five previous population-based environmental studies of
      semen quality were combined into one database at a university hospital in
      Denmark. PATIENT(S): In total, 2,139 men provided data to the database.
      INTERVENTION(S): Data on semen and blood samples and information on lifestyle and
      reproductive factors, including body mass index (BMI), were collected. MAIN
      OUTCOME MEASURE(S): Semen quality (volume, concentration, total sperm count, and
      motility) and serum concentration of sex hormones. RESULT(S): The T and inhibin B
      serum concentrations were 25%-32% lower in obese men in comparison with normal
      weight men, whereas the E(2) concentration was 6% higher in obese men. Overweight
      men (BMI, 25.1-30.0 kg/m(2)) had a slightly lower adjusted sperm concentration
      and total sperm count than did men with a normal BMI (20.0-25.0 kg/m(2)), but no
      reduction in sperm count was observed among the obese men. CONCLUSION(S): These
      results corroborate earlier findings that overweight and obese men have a
      markedly changed sex hormone profile in serum, whereas reduction of semen
      quality, if any, was marginal and below the detection limit of this large study.

PMID- 18068161
TI  - Resumption of mitosis in frozen-thawed embryos is not related to the chromosomal
      constitution.
AB  - OBJECTIVE: To study the relation between the resumption of mitosis after thaw and
      chromosomal constitution in frozen-thawed embryos. In addition, to evaluate the
      correlation among the three parameters of resumption of mitosis after thaw,
      postthaw blastomere loss, and multinucleation. DESIGN: Frozen-thawed embryos were
      morphologically evaluated at thaw and after 24 hours of culture. Then,
      fluorescence in situ hybridization (FISH) analysis, including enumeration of 13
      chromosomes, was performed by using a combination of peptide nucleic acid and DNA
      probes. SETTING: In vitro fertilization laboratory. PATIENT(S): Forty IVF and/or
      intracytoplasmic sperm injection patients. INTERVENTION(S): Embryo thawing,
      morphological evaluation, and fluorescence in situ hybridization analysis for
      aneuploidy screening. MAIN OUTCOME MEASURE(S): Resumption of mitosis, blastomere
      loss, multinucleation, and chromosome enumeration. RESULT(S): No difference was
      observed in the chromosomal constitution of embryos with and without resumption
      of mitosis. Neither was the postthaw blastomere loss connected to the chromosomal
      constitution. The resumption of mitosis was not associated with postthaw loss of
      blastomeres or with multinuclearity. CONCLUSION(S): Resumption of mitosis and
      blastomere loss of frozen-thawed embryos is not related to chromosome aberrations
      in the embryo. Further, the resumption of mitosis is not correlated with
      multinucleation. However, the high incidence of multinucleated embryos after
      thawing indicates that the freezing and thawing procedure may affect this
      condition.

PMID- 18068162
TI  - Impact of early cleaved zygote morphology on embryo development and in vitro
      fertilization-embryo transfer outcome: a prospective study.
AB  - OBJECTIVE: To evaluate the impact of the first division morphology on embryo
      development and IVF-embryo transfer outcome. DESIGN: Prospective study. SETTING:
      Teaching hospital, France. PATIENT(S): All zygotes from 201 couples were checked
      for early cleavage. We defined as "even," early cleaved (EC) zygotes with 2 cells
      of even size; as "uneven," EC zygotes with 2 cells of uneven size; and as
      "fragmented," EC zygotes with more than 20% fragmentation rate. Day 2 embryo
      quality was assessed as "top" embryo or "non-top," with the evaluation of
      multinucleated blastomeres. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Day 2
      embryo quality, pregnancy and implantation rates. RESULT(S): Among EC zygotes,
      59.1% were even, 13.0% were uneven, and 27.9% were fragmented. Even EC yielded
      more "top" embryos and less multinucleated blastomere embryos than uneven EC
      (77.0% vs. 46.3%) and fragmented EC (77.0% vs. 13.9%). The 125 double embryo
      transfers that comprised at least one embryo derived from even EC zygote led to
      higher pregnancy rate (PR) (64.0% vs. 43.4%) and implantation rate (42.0% vs.
      27.6%) compared to the 76 double embryo transfers with embryos derived from
      breakdown or 2PN zygotes. CONCLUSION(S): The morphology of the early cleaved
      zygote is involved in embryo development. Evaluation of this morphology is an
      effective and valuable method of assessing the embryo quality.

PMID- 18068163
TI  - Spectrotemporal changes in electrical activity of myometrium due to recombinant
      follicle-stimulating hormone preparations follitropin alfa and beta.
AB  - OBJECTIVE: To investigate the effects of follitropin alfa and beta on the
      myoelectrical activity of rat myometrium using signal-processing techniques.
      DESIGN: Prospective, placebo-controlled study. SETTING: Animal and pharmacology
      laboratory at Inonu University. ANIMAL(S): Forty-five female Wistar albino rats.
      INTERVENTION(S): Thirty of 45 animals involved in the experiment were registered
      as the superovulation group. After two successive normal estrous cycles, these
      animals were put into three equal subgroups. Group 1 was the control; animals
      were given 0.9% saline. Groups 2 and 3 were treated with follitropin alfa (Gonal
      f) and follitropin beta (Puregon), respectively. The other 15 animals were
      ovariectomized (OVX) and subjected to the same protocol. The uterine
      myoelectrical signals were recorded and analyzed using a Matlab environment. MAIN
      OUTCOME MEASURE(S): Power/second, variance, and the effects of recombinant human
      follicle-stimulating hormone (FSH) on myoelectrical signals were assessed through
      temporal, spectral, and joint time-frequency analysis. The uterine endometrium
      and ovarian morphology were also assessed concerning primary follicles, antral
      follicles, and corpora lutea. RESULT(S): The power and some characteristic
      spectral components of myoelectrical signal were reduced with the administration
      of follitropin alfa and beta. No statistically significant difference was
      detected between endometrial and ovarian histology of the rats treated with these
      follitropins. CONCLUSION(S): Uterine myoelectrical signals change with
      administration of recombinant human FSH preparations. Follitropin beta and, more
      precisely, follitropin alfa suppress the spectral components and power of the
      myoelectrical signals, which provides uterine quiescence.

PMID- 18068164
TI  - Regulation of natural-killer cell cytotoxicity and enhancement of complement
      factors in the spontaneously aborted mouse placenta.
AB  - OBJECTIVE: To evaluate the cytotoxicity of uterine natural killer (NK) cells and
      identify major biological factors fluctuating in the spontaneously aborted
      placenta. DESIGN: Spontaneously aborted placentae were examined by using
      histology, molecular biology, and DNA microarray analysis. SETTING: Laboratories
      and animal center at a medical college. ANIMAL(S): C57BL/6 mice. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Up-regulation of the inhibitory system of uterine
      NK cells and enhancement of complement factors in aborted placenta. RESULT(S): In
      uteri on day 14 of pregnancy, 9.69% +/- 11.6% (+/-SD) implantation sites
      spontaneously aborted. Labyrinthine trophoblasts at abortion sites had nuclei
      that were positive for DNA fragment detection, as well as apoptotic morphology.
      Many uterine NK cells were present at abortion sites, but cytotoxic factors such
      as perforin, granzyme B, and Fas-Fas ligand were expressed at very low levels. In
      contrast, the expression level of Ly49 NK-cell receptors, which mediate an
      inhibitory signal for cytotoxicity, was enhanced at abortion sites.
      Deoxyribonucleic acid microarray analysis showed that adipsin, an activating
      enzyme for complement component C3, was strongly enhanced in aborted placenta,
      and positive reactions for adipsin and C3 were confirmed by immunohistochemistry.
      CONCLUSION(S): In the process of spontaneous abortion, the cytotoxicity of
      uterine NK cells is inhibited, and the innate immune system through adipsin and
      complement C3 appears to be influential.

PMID- 18068165
TI  - Sperm nuclear apoptotic DNA fragmentation in men with testicular cancer.
AB  - OBJECTIVE: To verify whether sperm from patients with a seminoma and patients
      with a non-seminoma present with an increased rate of apoptotic DNA
      fragmentation, when compared with men without testicular cancer and who had
      fathered a child in the 2 years preceding the study. DESIGN: Controlled
      prospective study. SETTING: Patients referred to a sperm bank in an academic
      research environment. PATIENT(S): Men with a diagnosed seminoma, men with a
      diagnosed non-seminoma, both after orchiectomy and before adjuvant therapy, and
      men with proven paternity in the 2 previous years. MAIN OUTCOME MEASURE(S): Rate
      of nuclear apoptotic sperm DNA fragmentation as assessed by TUNEL (terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assay, classified
      as positive (with DNA fragmentation) or negative (without DNA fragmentation).
      RESULT(S): Of the 48 men with testicular cancer included in the study, 29 (60.4%)
      presented a non-seminoma and 19 (39.6%) a seminoma. Patients with non-seminoma
      presented with lower progressive sperm motility than the control group (57.4% and
      66.3%, respectively), but both were still within normal ranges. Sperm
      concentration was lower in seminoma (31.2 x 10(6)/mL) and in non-seminoma (20.6 x
      10(6)/mL) when compared with the control group (78.1 x 10(6)/mL), but values did
      not differ between the two testicular cancer groups. Sperm morphology was lower
      in patients with non-seminoma than in the control group (10% and 13.1%,
      respectively). Results for sperm nuclear apoptotic DNA fragmentation (mean;
      standard deviation) were 12.6%; 4.5% for the control group, 12.2%; 5.5% for the
      non-seminoma group, and 12.5%; 6.4% for the seminoma group. No differences were
      found between the three groups. CONCLUSION(S): Our results demonstrate that the
      presence of a seminoma or a non-seminoma is not associated with an increase in
      sperm apoptotic DNA fragmentation.

PMID- 18068166
TI  - Does high body mass index increase the risk of miscarriage after spontaneous and
      assisted conception? A meta-analysis of the evidence.
AB  - OBJECTIVE: To investigate the association between obesity and miscarriage.
      DESIGN: Meta-analysis. SETTING: The Academic Unit of Reproductive and
      Developmental Medicine, The University of Sheffield, United Kingdom. PATIENT(S):
      Obese and overweight patients who had miscarriage after spontaneous or assisted
      conception, compared with patients with a normal body mass index.
      INTERVENTION(S): A systematic review was conducted for all relevant articles in
      MEDLINE from 1964 to September 2006 and in EMBASE from 1974 to September 2006,
      using a combination of the following search terms: obesity/obes*/obes$/BMI,
      miscarriage/abortion/pregnancy, IVF, clomifene/clomiphene,
      gonadotrophins/gonadotrop*/gonadotrop$. MAIN OUTCOME MEASURE(S): Pregnancy loss
      at <20 weeks of gestation. RESULT(S): Sixteen studies were included in the meta
      analysis. Patients with a body mass index of > or =25 kg/m(2) had significantly
      higher odds of miscarriage, regardless of the method of conception (odds ratio,
      1.67; 95% confidence interval, 1.25-2.25). Subgroup analysis from a limited
      number of studies suggested that this group of women may also have significantly
      higher odds of miscarriage after oocyte donation (odds ratio, 1.52; 95%
      confidence interval, 1.10-2.09) and ovulation induction (odds ratio, 5.11; 95%
      confidence interval, 1.76-14.83). There was no evidence for increased odds of
      miscarriage after IVF-intracytoplasmic sperm injection. CONCLUSION(S): There is
      evidence that obesity may increase the general risk of miscarriage. However,
      there is insufficient evidence to describe the effect of obesity on miscarriage
      in specific groups such as those conceiving after assisted conception.

PMID- 18068167
TI  - Identification of human spermatogenesis-related proteins by comparative proteomic
      analysis: a preliminary study.
AB  - OBJECTIVE: To identify human spermatogenesis-related proteins. DESIGN:
      Prospective study. SETTING: University research laboratory. PATIENT(S): Three
      fertile men with normal spermatogenesis, 3 azoospermic patients with sloughing
      and disorganization of germ cells. INTERVENTION(S): Testicular tissue samples
      were collected by biopsy after informed consent. MAIN OUTCOME MEASURE(S): The
      protein expressional profiles of human testes of fertile men and azoospermic
      patients were compared using a proteomic approach by combining two-dimensional
      gel electrophoresis analyses and mass spectrometry. Bioinformatic analysis helped
      to reveal the regulation pathway. Expression of some selected proteins in normal
      and pathological testes was analyzed by immunohistochemistry. RESULT(S): Ten
      protein spots were identified as expressing differentially between the normal
      testes and pathological testes with sloughing and disorganization of germ cells;
      these included the phospholipid hydroperoxide glutathione peroxidase,
      peroxiredoxin 4 (Prx4), heat shock protein beta-1 (HSP27), and cathepsin D
      (CTSD). Bioinformatic analysis revealed that many differentially expressed
      proteins participate in cellular proliferation, apoptosis, and cell death and
      helped us to focus on a few of them. Immunohistochemical analysis of Prx4, HSP27,
      and CTSD confirmed the results obtained by proteomic analysis. CONCLUSION(S):
      These 10 proteins may help in elucidating the pathways involved in human
      spermatogenesis.

PMID- 18068168
TI  - A code of ethics for the fistula surgeon.
AB  - Vesicovaginal fistulas from obstructed labor no longer exist in wealthy
      industrialized countries. In the impoverished countries of sub-Saharan Africa and
      south Asia obstetric fistulas continue to be a prevalent clinical problem. As
      many as 3.5 million women may suffer from this condition and few centers exist
      that can provide them with competent and compassionate surgical repair of their
      injuries. As this situation has become more widely known in the industrialized
      world, increasing numbers of surgeons have begun traveling to poor countries to
      perform fistula operations. To date, these efforts have been carried out largely
      by well-intentioned individuals, acting alone. An international community of
      fistula surgeons who share common goals and values is still in the process of
      being created. To help facilitate the development of a common ethos and to
      improve the quality of care afforded to women suffering from obstetric fistulas,
      we propose a Code of Ethics for fistula surgeons that embraces the fundamental
      principles of beneficence, non-maleficence, respect for personal autonomy, and a
      dedication to the pursuit of justice.

PMID- 18068169
TI  - Laparoscopic loop ligature for selective therapy in heterotopic interstitial and
      intrauterine pregnancy following in-vitro fertilization and embryo transfer.

PMID- 18068170
TI  - Thrombophilia-associated gene mutations in women with pregnancies complicated by
      fetal neural tube defects.

PMID- 18068171
TI  - Anemia and iron deficiency in pregnant Ghanaian women from urban areas.
AB  - OBJECTIVES: To determine the prevalence and identify risk factors for iron
      deficiency and anemia in pregnant Ghanaian women from urban areas. METHODS: A
      cross-sectional study of 452 healthy pregnant women receiving prenatal care in
      Accra, Ghana, was conducted. A sociodemographic health questionnaire was
      performed and hematologic parameters were measured. Logistic regression methods
      were used to identify risk factors for anemia and iron status. RESULTS: Complete
      data were available for 428 women. Anemia (hemoglobin <11 g/dL) was present in
      144 (34%), iron deficiency (ferritin < or =16 microg/L) in 69 (16%), and iron
      deficiency anemia in 32 (7.5%) women. The adjusted odds ratio (OR) for anemia was
      3.4 and 9.8 if iron deficiency and malaria parasitemia were present,
      respectively; the OR was 0.6 if women were at > or =36 weeks of pregnancy. The
      adjusted OR for iron deficiency was 2.7 if women were at > or =36 weeks of
      pregnancy and 0.12 if they had sickle trait. CONCLUSION: Although anemia and iron
      deficiency remain substantial problems in pregnant Ghanaian women from urban
      areas, their prevalence is less than previously reported.

PMID- 18068172
TI  - Relationship of cytopathology and cervical infection to outcome of in-vitro
      fertilization and embryo transfer.
AB  - OBJECTIVE: To determine whether a relationship exists between in-vitro
      fertilization and embryo transfer (IVF-ET) outcome and cervical infection or
      presence of human papillomavirus (HPV). METHOD: Cervical scrapes, digital
      colposcopies, and cervical biopsies were performed in 1044 Chinese women
      undergoing IVF for tubal infertility or, in their partners, abnormal semen. The
      pregnant (n=415) and nonpregnant (n=629) groups differed neither in clinical
      signs of cervical inflammation nor in rate of HPV detection. RESULTS: There were
      no associations between IVF-ET outcome and infection rate, degree of
      cytopathologic abnormality, detection of HPV, or results of digital colposcopy
      and cervical biopsy. Cytologic results did not correlate with any of the clinical
      parameters of IVF-ET. CONCLUSIONS: No association was found between IVF-ET
      outcome and cervical infection, cytopathologic result, HPV detection, or result
      from the colposcopy or biopsy. Extensive testing and treatment for cervical
      infection do not appear necessary in IVF-ET candidates.

PMID- 18068173
TI  - Genetic and phenotypic differences between isolates of Haemonchus contortus in
      Australia.
AB  - We believe this study is the first to consider the genetic and phenotypic
      divergence between isolates of Haemonchus contortus in Australia. Microsatellite
      markers have been used to investigate genetic divergence, whilst phenotypic
      divergence has been considered through individual worm morphology, isolate life
      history traits and the effect of isolates upon the host. The results are
      discussed in the context of the likely introduction of H. contortus to Australia,
      its recent isolation, and the characteristics of sheep and goat farming which
      might act to either isolate or distribute parasites. We conclude that there is
      significant observable genetic divergence between isolates of H. contortus in
      Australia. The divergence may have been under-estimated in this study due to a
      variety of factors. Phenotypic divergence is also observed, and potentially has
      significant implications for both economic losses due to haemonchosis on
      individual properties and for decisions regarding the regulation of stock
      movements in Australia.

PMID- 18068174
TI  - Genetic screening of the LPL gene in hypertriglyceridaemic patients.
AB  - Serum triglyceride (TG) level is an important independent risk factor for
      coronary heart disease, with the lipoprotein lipase (LPL) enzyme playing the
      major role in regulating the catabolism of TG rich lipoproteins. The complete
      sequence analysis of the LPL gene was carried out on 19 individuals with extreme
      hypertriglyceridaemia (HTG; TG>14 mmol/l) with a total of 42 sequence variants
      being identified, a number of which are novel to this study. A total of eight
      patients were shown to have functional variants (p.D36N, p.R197H, p.N318S,
      p.V340I) that alter amino acids at 11 of the 16 LPL alleles. Multiplex ligation
      dependent probe amplification (MLPA) analysis showed no exonic deletion or
      duplications in this population. Further analysis of the p.N318S (also called
      N291S) variant identified in the sequencing screen, in larger case and control
      populations, identified this mutation to be strongly associated with HTG. This
      study has produced a more comprehensive SNP map of LPL and its surrounding area
      and identified p.N318S as a major predisposing factor to HTG in the Northern
      Irish population.

PMID- 18068175
TI  - The free diffusion of macromolecules in tissue-engineered skeletal muscle
      subjected to large compression strains.
AB  - Pressure-related deep tissue injury (DTI) represents a severe pressure ulcer,
      which initiates in compressed muscle tissue overlying a bony prominence and
      progresses to more superficial tissues until penetrating the skin. Individual
      subjects with impaired motor and/or sensory capacities are at high risk of
      developing DTI. Impaired diffusion of critical metabolites in compressed muscle
      tissue may contribute to DTI, and impaired diffusion of tissue damage biomarkers
      may further impose a problem in developing early detection blood tests. We
      hypothesize that compression of muscle tissue between a bony prominence and a
      supporting surface locally influences the diffusion capacity of muscle. The
      objective of this study was therefore, to determine the effects of large
      compression strains on free diffusion in a tissue-engineered skeletal muscle
      model. Diffusion was measured with a range of fluorescently labeled dextran
      molecules (10, 20, 150kDa) whose sizes were representative of both hormones and
      damage biomarkers. We used fluorescence recovery after photobleaching (FRAP) to
      compare diffusion coefficients (D) of the different dextrans between the
      uncompressed and compressed (48-60% strain) states. In a separate experiment, we
      simulated the effects of local partial muscle ischemia in vivo, by reducing the
      temperature of compressed specimens from 37 to 34 degrees C. Compared to the D in
      the uncompressed model system, values in the compressed state were significantly
      reduced by 47+/-22% (p<0.02). A 3 degrees C temperature decrease further reduced
      D in the compressed specimens by 10+/-6% (p<0.05). In vivo, the effects of large
      strains and ischemia are likely to be summative, and hence, the present findings
      suggest an important role of impaired diffusion in the etiology of DTI, and
      should also be considered when developing biochemical screening methods for early
      detection of DTI.

PMID- 18068176
TI  - Risk-based approach for the transfer of quantitative methods: bioanalytical
      applications.
AB  - The transfer of analytical methods from a sending laboratory to a receiving one
      requires to guarantee that this last laboratory will obtain accurate results.
      Undeniably method transfer is the ultimate step before routine implementation of
      the method at the receiving site. The conventional statistical approaches
      generally used in this domain which analyze separately the trueness and precision
      characteristics of the receiver do not achieve this. Therefore, this paper aims
      first at demonstrating the applicability of two recent statistical approaches
      using total error-based criterion and taking into account the uncertainty of the
      true value estimate of the sending laboratory, to the transfer of bioanalytical
      methods. To achieve this, they were successfully applied to the transfer of two
      fully automated liquid chromatographic method coupled on-line to solid-phase
      extraction. The first one was dedicated to the determination of three
      catecholamines in human urine using electrochemical detection, and the second one
      to the quantitation of N-methyl-laudanosine in plasma using fluorescence
      detection. Secondly, a risk-based evaluation is made in order to understand why
      classical statistical approaches are not sufficient to provide the guarantees
      that the analytical method will give most of the time accurate results during its
      routine use. Finally, some recommendations for the transfer studies are proposed.

PMID- 18068177
TI  - Determination of the antioxidant capacity of active food packagings by in situ
      gas-phase hydroxyl radical generation and high-performance liquid chromatography
      fluorescence detection.
AB  - An experimental laboratory-made assembly to determine for the first time the
      antioxidant capacity with respect to hydroxyl (OH*) radicals of several new
      active packagings directly in the materials has been developed. Gas-phase OH*
      radicals are generated by UV-light irradiation of an aqueous H(2)O(2) aerosol.
      After on-line reaction with up to eight parallel test samples, remaining OH* is
      quantitatively trapped by a salicylic acid solution, and antioxidant capacity is
      indirectly assessed by HPLC-fluorescence determination of the high sensitive 2,5
      dihydroxybenzoic acid formed. Several natural essential oils as well as active
      plastic films including in their formulation such oils have been subjected to
      oxidation. Polymers containing clove and oregano were the most efficient ones (up
      to 7.2 and 4.7 times, respectively, more antioxidant than blanks), whereas
      rosemary, citronella and propolis showed average efficiency. On the other hand,
      active materials containing ferulic acid, quercetin, catechin and thymol, as well
      as commercial active bags with ethylene-absorption properties, showed limited or
      none antioxidant protection. Experimental results and full details about
      experimental assembly are given.

PMID- 18068178
TI  - Stir bar sorptive extraction coupled to thermodesorption-gas chromatography-mass
      spectrometry for the determination of insect repelling substances in water
      samples.
AB  - Stir bar sorptive extraction (SBSE) in combination with thermodesorption-gas
      chromatography-mass spectrometry (TD-GC-MS) was applied for the determination of
      eight insect repellents and synergists in water samples. The stir bar coated with
      polydimethylsiloxane (PDMS) was added to 20 mL of water sample with 4 g NaCl and
      stirred at 1000 rpm for 180 min. Then, the stir bar was subjected to TD-GC-MS.
      SBSE parameters (ionic strength, presence of organic solvent and time) were
      optimised. Blank contamination and carryover problems were also studied. The
      method affords detection limits between 0.5 and 30 ng/L, except for dimethyl
      phthalate (DMP) (150 ng/L) due to blank contamination problems. It shows good
      linearity with correlation coefficients over 0.997 and reproducibility (RSD)
      below 20%. The extraction efficiencies were between 29% for DMP and 80% for di-n
      propyl isocinchomeronate (R-326). The feasibility of the method was tested by
      analysing real samples such as lake water, river water and wastewater.

PMID- 18068179
TI  - Field-amplified sample stacking for the detection of chemical warfare agent
      degradation products in low-conductivity matrices by capillary electrophoresis
      mass spectrometry.
AB  - Preconcentration of chemical warfare agent degradation products (alkylphosphonic
      acids and alkyl alkylphosphonic acids) in low-conductivity matrices (purified
      water, tap water and local river water) by field-amplified sample stacking (FASS)
      was developed for capillary electrophoresis (CE) coupled to ion trap mass
      spectrometry. FASS was performed by adding a mixture of HCOONH(4) and NH(4)OH in
      appropriate concentrations to the sample. This allowed to control the
      conductivity and the pH of the sample in order to obtain FASS performances that
      are independent of analyte concentration. The influence of different parameters
      on FASS (sample to background electrolyte (BGE) conductivity ratio, injection
      volume and concentration of BGE) was studied to determine the optimal conditions
      and was rationalized by using the theoretical model developed by Burgi and Chien.
      A good correlation was obtained between the bulk electroosmotic velocity
      predicted by this model and the experimental value deduced from the migration
      time of the electroosmotic flow marker detected by mass spectrometry (MS). This
      newly developed method was successfully applied to the analysis of tap water and
      local river water fortified with the analytes and provided a 10-fold sensitivity
      enhancement in comparison to the signal obtained without preconcentration
      procedure. The quite satisfactory repeatability and linearity for peak areas
      obtained in the 0.5-5 microg mL(-1) concentration range allow quantitative
      analysis to be implemented. Limits of detection of 0.25-0.5 microg mL(-1) for the
      alkyl alkylphosphonic acids and of 0.35-5 microg mL(-1) for the alkylphosphonic
      acids were reached in tap water and river water.

PMID- 18068180
TI  - Layer-by-layer fabrication of broad-band superhydrophobic antireflection coatings
      in near-infrared region.
AB  - Broad-band superhydrophobic antireflective (AR) coatings in near infrared (NIR)
      region were readily fabricated on silicon or quartz substrates by a layer-by
      layer (LbL) assembly technique. First, a porous poly(diallyldimethylammonium
      chloride) (PDDA)/SiO2 nanoparticle multilayer coating with AR property was
      prepared by LbL deposition of PDDA and 200 nm SiO2 nanoparticles. PDDA was then
      alternately assembled with sodium silicate on the PDDA/SiO2 nanoparticle coating
      to prepare a two-level hierarchical surface. Superhydrophobic AR coating with a
      water contact angle of 154 degrees was finally obtained after chemical vapor
      deposition of a layer of fluoroalkylsilane on the hierarchical surface. Quartz
      substrate with the as-fabricated superhydrophobic AR coating has a maximal
      transmittance above 98% of incidence light in the NIR region, which is increased
      by five percent compared with bare quartz substrate. Simultaneously, the
      superhydrophobic property endows the AR coating with water-repellent ability.
      Such superhydrophobic AR coatings can effectively avoid the disturbance of water
      vapor on their AR property and are expected to be applicable under humid
      environments.

PMID- 18068181
TI  - Preparation of Ru-doped SnO2-supported Pt catalysts and their electrocatalytic
      properties for methanol oxidation.
AB  - Ru-doped SnO2 nanoparticles were prepared by chemical precipitation and
      calcinations at 823 K. Due to high stability in diluted acidic solution, Ru-doped
      SnO2 nanoparticles were selected as the catalyst support and second catalyst for
      methanol electrooxidation. The micrograph, elemental composition, and structure
      of the Ru-doped SnO2 nanoparticles were characterized by scanning electron
      microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction,
      respectively. The electrocatalytic properties of the Ru-doped SnO2-supported Pt
      catalyst (Pt/Ru-doped SnO2) for methanol oxidation have been investigated by
      cyclic voltammetry. Under the same loading mass of Pt, the Pt/Ru-doped SnO2
      catalyst shows better electrocatalytic performance than the Pt/SnO2 catalyst and
      the best atomic ratio of Ru to Sn in Ru-doped SnO2 is 1/75. Additionally, the
      Pt/Ru-doped SnO2 catalyst possesses good long-term cycle stability.

PMID- 18068182
TI  - Chirality and helix stability of polyglutamic acid enantiomers.
AB  - In this work the chirality and the relative thermal stability of ordered micellar
      aggregates of poly-L- and poly-D-glutamic acids with the cationic surfactant
      C14TAB is examined. The complexed mesophases poly-L-Glu/C14TAB and poly-d
      Glu/C14TAB were characterized by circular dichroism (CD) in the temperature range
      10-70 degrees C for their chirality and thermal stability as well as by X-ray
      diffraction (XRD) for the micellar ordered structure. Low angle XRD analysis
      showed that both micellar aggregates poly-L-Glu/C14TAB and poly-D-Glu/C14TAB are
      hexagonally packed in a MCM-41 fashion with an intermicellar distance identical
      and equal to 3.55+/-0.10 nm. The CD spectra indicated that both complexes poly-L
      Glu/C14TAB and poly-D-Glu/C14TAB possess a mainly alpha-helix structure and are
      exact mirror images to each other. The same mirror images and a mainly alpha
      helix configuration were also observed by CD for the free poly-l- and poly-d
      glutamic acids at room temperature. As the temperature increases from 10 up to 70
      degrees C the alpha-helix of the poly-l-glutamic acid is gradually transformed to
      a mixture containing increased amounts of the 3(10)-helix while the alpha-helix
      structure of the poly-d-glutamic acid is constantly degenerated. In contrast the
      alpha-helices of the corresponding complexes poly-L-Glu/C14TAB and poly-d
      Glu/C14TAB are degenerated upon heating without appreciable increase of the 3(10)
      helices as an intermediate configuration. This difference in helix conservation
      is attributed to increase protection of the l-enantiomers, compared to d
      enantiomers, which might be related to the survival of l-aminoacids in the living
      world.

PMID- 18068183
TI  - Generation and characterisation of CD1d tetramer produced by a lentiviral
      expression system.
AB  - The alpha-galactosylceramide (alphaGalCer)-loaded CD1d tetramer remains the most
      powerful tool in identifying natural killer T (NKT) cells, a subpopulation of T
      cells that express an unusual semi-invariant T cell antigen receptor, and mediate
      a variety of proinflammatory and immunoregulatory functions. The difficulty of
      generating large amounts of the alphaGalCer-CD1d tetramer has limited its
      availability and consequently hampered the study of NKT cells. In this report, we
      used a lentiviral system to generate stable cell lines producing beta2m-CD1d
      single chain protein in large quantities and in a relatively short period of
      time. When the protein was loaded with alphaGalCer and tetramerised with
      fluorescence-labelled streptavidin, its ability to efficiently bind to NKT cells
      was confirmed both by phenotype analysis and functional study. The CD1d tetramer
      generated from these stable cell lines should facilitate a wide range of studies
      on the biology and clinical applications of CD1d-restricted NKT cells.

PMID- 18068184
TI  - Vitellogenesis in the hematophagous Dipetalogaster maxima (Hemiptera:
      Reduviidae), a vector of Chagas' disease.
AB  - Oocyte extracts of anautogenous Dipetalogaster maxima were chromatographed on an
      ion-exchange column in order to purify vitellin (Vt), the main insect yolk
      protein precursor. Purified Vt (Mr ~443 kDa) was composed of four subunits with
      approximate molecular weights of 174, 170, 50, and 44 kDa. Polyclonal anti-Vt
      antibody, which cross-reacted equally with fat body extracts and hemolymph
      vitellogenin (Vg), was used to measure the kinetics of Vg expression in the fat
      body and the levels in hemolymph. In addition, morphological and
      immunohistochemical changes that took place in the ovary during vitellogenesis
      were analyzed. The study was performed between 2 and 8 days post-ecdysis and
      between 2 and 25 days post-blood feeding. During the post-ecdysis period, D.
      maxima showed decreased synthesis of Vg and concomitantly, low levels of Vg in
      hemolymph (4.5 x 10(-3) microg/microl at day 4). After a blood meal, Vg synthesis
      in the fat body and its levels in hemolymph increased significantly, reaching an
      average of 19.5 microg/microl at day 20. The biochemical changes observed in the
      fat body and hemolymph were consistent with the histological and
      immunohistochemical finds. These studies showed noticeable remodeling of tissue
      after blood feeding.

PMID- 18068186
TI  - Crystal structure and mutational study of a unique SpoU family archaeal methylase
      that forms 2'-O-methylcytidine at position 56 of tRNA.
AB  - The conserved cytidine residue at position 56 of tRNA contributes to the
      maintenance of the L-shaped tertiary structure. aTrm56 catalyzes the 2'-O
      methylation of the cytidine residue in archaeal tRNA, using S-adenosyl-L
      methionine. Based on the amino acid sequence, aTrm56 is the most distant member
      of the SpoU family. Here, we determined the crystal structure of Pyrococcus
      horikoshii aTrm56 complexed with S-adenosyl-L-methionine at 2.48 A resolution.
      aTrm56 consists of the SPOUT domain, which contains the characteristic deep
      trefoil knot, and a unique C-terminal beta-hairpin. aTrm56 forms a dimer. The S
      adenosyl-L-methionine binding and dimerization of aTrm56 were similar to those of
      the other SpoU members. A structure-based sequence alignment revealed that aTrm56
      conserves only motif II, among the four signature motifs. However, an essential
      Arg16 residue is located at a novel position within motif I. Biochemical assays
      showed that aTrm56 prefers the L-shaped tRNA to the lambda form as its substrate.

PMID- 18068185
TI  - Calpain inhibition attenuates right ventricular contractile dysfunction after
      acute pressure overload.
AB  - Right ventricular contractile failure from acute RV pressure overload is an
      important cause of morbidity and mortality, but the mechanism of RV failure in
      this setting is incompletely defined. We hypothesized that RV dysfunction from
      acute RV pressure overload is, in part, due to activation of calpain, and that
      calpain inhibition would therefore attenuate RV dysfunction. Anesthetized, open
      chest pigs were treated with the calpain inhibitor MDL-28170 or with inactive
      vehicle, and then subjected to acute RV pressure overload for 90 min. RV
      contractile function was assessed by the regional Frank-Starling relation. RV
      myocardial tissue was analyzed for evidence of calpain activation and calpain
      mediated proteolysis. RV pressure overload caused severe contractile dysfunction,
      along with significant alterations in the endogenous calpain inhibitor
      calpastatin typical of calpain activation. MDL-28170 attenuated RV free wall
      dysfunction by more than 50%. However, there were no differences in degradation
      of spectrin, desmin, troponin-I or SERCA2 between SHAM operated pigs and pigs
      subjected to acute RV pressure overload, or between vehicle and MDL-28170 treated
      pigs. Acute RV pressure overload causes calpain activation, and RV contractile
      dysfunction from acute RV pressure overload is attenuated by the calpain
      inhibitor MDL-28170; however, the effect is not explained by inhibition of
      calpain-mediated degradation of spectrin, desmin, troponin-I or SERCA2. Because
      this is the first report of any agent that can directly attenuate RV contractile
      dysfunction in acute RV pressure overload, further investigation of the mechanism
      of action of MDL-28170 in this setting is warranted.

PMID- 18068187
TI  - The flagellar filament structure of the extreme acidothermophile Sulfolobus
      shibatae B12 suggests that archaeabacterial flagella have a unique and common
      symmetry and design.
AB  - Archaea, constituting a third domain of life between Eubacteria and Eukarya,
      characteristically inhabit extreme environments. They swim by rotating flagellar
      filaments that are phenomenologically and functionally similar to those of
      eubacteria. However, biochemical, genetic and structural evidence has pointed to
      significant differences but even greater similarity to eubacterial type IV pili.
      Here we determined the three-dimensional symmetry and structure of the flagellar
      filament of the acidothermophilic archaeabacterium Sulfolobus shibatae B12 using
      transmission electron microscopy (TEM) and scanning transmission electron
      microscopy (STEM). Processing of the cryo-negatively stained filaments included
      analysis of their helical symmetry and subsequent single particle reconstruction.
      Two filament subunit packing arrangements were identified: one has helical
      symmetry, similar to that of the extreme halophile Halobacterium salinarum, with
      ten subunits per 5.3 nm repeat and the other has helically arranged stacked disks
      with C(3) symmetry and 12 subunits per repeat. The two structures are related by
      a slight twist. The S. shibatae filament has a larger diameter compared to that
      of H. salinarum, at the opposite end of the archaeabacterial phylogenetic
      spectrum, but the basic three-start symmetry and the size and arrangement of the
      core domain are conserved and the filament lacks a central channel. This
      similarity suggests a unique and common underlying symmetry for archaeabacterial
      flagellar filaments.

PMID- 18068188
TI  - The protective effect of risk factors against stroke severity.

PMID- 18068189
TI  - CSF findings in patients with voltage gated potassium channel antibody associated
      limbic encephalitis.
AB  - Recently, a new subtype of limbic encephalitis (LE) has been described,
      serologically characterized by the presence of antibodies against voltage gated
      potassium channels (VGKC, to be called VGKC-LE). Only little is known about CSF
      findings in this new disorder. Here we report the results of 29 lumbar punctures
      in 17 patients with VGKC-LE. Slight pleocytosis, mainly consisting of lymphocytes
      and monocytes, and elevated total protein concentrations were present in 41 and
      47%, respectively. Intrathecal immunoglobulin (Ig) synthesis as defined by the
      presence of CSF-specific oligoclonal IgG bands, an increased IgG index, or an
      elevated IgG, IgA, or IgM ratio, was not detected in any of the patients, but
      dysfunction of the blood-CSF barrier was found in 35%. CSF findings were normal
      in 23%. CONCLUSIONS: Unlike paraneoplastic LE, VGKC-LE is not frequently
      associated with intrathecal Ig production or markedly elevated white cell counts.
      Thus, normal CSF findings do not preclude the disease. VGKC-Ab should, therefore,
      be determined whenever LE is clinically suspected, irrespective of the presence
      or absence of inflammatory CSF changes.

PMID- 18068190
TI  - Neuroprotective effect of diazoxide on brain injury induced by cerebral
      ischemia/reperfusion during deep hypothermia.
AB  - OBJECT: The purpose of this study was to determine the effects of diazoxide on
      apoptosis and the relative mechanisms in a model of brain injury induced by
      cerebral ischemia/reperfusion (I/R) during deep hypothermia. METHODS: Three-week
      old Sprague-Dawley male rats were randomly and equitably divided into sham
      operated group, placebo-treated group and diazoxide-treated group respectively.
      Specific examination of the regional cerebral blood flow (rCBF) was measured in
      the three groups continuously during the operation by laser Doppler flowmetry.
      Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) was
      showed DNA fragmentation. The mRNA expressions of cytochrome c and full-length
      caspase-3 were determined by RT-PCR, while the protein expressions of cytochrome
      c and cleaved caspase-3 were determined by immunohistochemistry at 1 h, 6 h, 24
      h, 72 h and 7 days after I/R, respectively. Cytosolic release of cytochrome c at
      24 h after I/R was also confirmed by Western blot. RESULTS: rCBF was
      significantly decreased in both of placebo-treated and diazoxide-treated group
      just after ischemia in the time interval 0-5 min, and had no obvious changes in
      all the time intervals during the operation. Diazoxide preconditioning
      significantly decreased the percentage of TUNEL-positive staining cells. The mRNA
      expressions of cytochrome c and full-length caspase-3 in diazoxide-treated group
      were significantly decreased. In addition, diazoxide provided a significant
      reduction in the protein expressions of cytochrome c and cleaved caspase-3.
      CONCLUSION: These results suggested that the neuroprotective effects of diazoxide
      against cerebral I/R injury during deep hypothermia correlated with the reduction
      of DNA fragmentation, prevention of mitochondrial cytochrome c release and
      inhibition of caspase-3 activation.

PMID- 18068191
TI  - The clinical course of multiple sclerosis patients in Hong Kong.
AB  - BACKGROUND: Multiple sclerosis (MS) has a low prevalence in Hong Kong. OBJECTIVE:
      To reassess MS prevalence in Hong Kong and to examine associated risk factors for
      relapsing-remitting type MS patients to reach Kurtzke's Extended Disability
      Status Scale (EDSS) of 6.0, i.e. when walking aid was needed. DESIGN:
      Retrospective observational study on MS patients over 11 years. SETTING: Three
      tertiary hospitals in Hong Kong. RESULTS: A hundred and six patients were
      recruited. Female to male ratio was 3.2:1 and the prevalence was 4.8 per 100,000.
      95 were relapsing-remitting (RR) type. The mean disease duration was 12.7 years
      (range: 1-45 years) and the duration of follow up was 11.0+/-0.8 (mean+/-SE)
      years. The initial mean EDSS was 1.59 and the latest mean EDSS was 4.26. 38 (40%)
      RR type MS patients progressed to EDSS 6.0 after a mean duration of 6.0 years.
      With Cox regression analysis, patients with older age (>35y) of onset (HR 2.57;
      95% CI:1.29-5.11), higher EDSS of 2.0 or more upon presentation (HR 2.19; 95%CI:
      1.12-4.26) were associated with progression to EDSS of 6.0, while there was a
      tendency towards slower disease progression for patients initially presenting
      with optic symptoms (HR 0.52; 95%CI: 0.23-1.16). The number of relapses and use
      of interferon could not be shown to have significant effect on disease
      progression. CONCLUSIONS: The local period prevalence ratio of MS was 4.8 per
      100,000. Older age of onset and higher EDSS upon initial presentation were
      independent predictors for progression to EDSS of 6.0.

PMID- 18068192
TI  - A hybrid cellular automaton model of clonal evolution in cancer: the emergence of
      the glycolytic phenotype.
AB  - We present a cellular automaton model of clonal evolution in cancer aimed at
      investigating the emergence of the glycolytic phenotype. In the model each cell
      is equipped with a micro-environment response network that determines the
      behaviour or phenotype of the cell based on the local environment. The response
      network is modelled using a feed-forward neural network, which is subject to
      mutations when the cells divide. This implies that cells might react differently
      to the environment and when space and nutrients are limited only the fittest
      cells will survive. With this model we have investigated the impact of the
      environment on the growth dynamics of the tumour. In particular, we have analysed
      the influence of the tissue oxygen concentration and extra-cellular matrix
      density on the dynamics of the model. We found that the environment influences
      both the growth and the evolutionary dynamics of the tumour. For low oxygen
      concentration we observe tumours with a fingered morphology, while increasing the
      matrix density gives rise to more compact tumours with wider fingers. The
      distribution of phenotypes in the tumour is also affected, and we observe that
      the glycolytic phenotype is most likely to emerge in a poorly oxygenated tissue
      with a high matrix density. Our results suggest that it is the combined effect of
      the oxygen concentration and matrix density that creates an environment where the
      glycolytic phenotype has a growth advantage and consequently is most likely to
      appear.

PMID- 18068194
TI  - Role of cation-pi interactions in single chain 'all-alpha' proteins.
AB  - Cation-pi interactions are known to be important contributors to protein
      stability and ligand-protein interactions. In this study, we have analyzed the
      influence of cation-pi interactions in single chain 'all-alpha' proteins. We
      observed 135 cation-pi interactions in a data set of 75 proteins. No significant
      correlation was observed between the total number of amino acid residues and
      number of cation-pi interactions. These interactions are mainly formed by long
      range contacts and there is preference of Arg over Lys in these interactions. Arg
      Phe interactions are predominant among the various pairs analyzed. Despite the
      scarcity of interactions involving Trp, the average energy for Trp-cation
      interactions, was quite high. This information implies that the cation-pi
      interactions involving Trp, maybe of high relevance to the proteins. Secondary
      structure analysis reveals that cation-pi interactions are formed preferably
      between residues, in which at least one of them, is in the secondary structure of
      alpha-helical segments. Among the various types of folds of 'all-alpha' proteins
      considered for the analysis, proteins belonging to alpha-alpha superhelix fold
      have the highest number of cation-pi interaction forming residues.

PMID- 18068193
TI  - A comparison of random vs. chemotaxis-driven contacts of T cells with dendritic
      cells during repertoire scanning.
AB  - Generating adaptive immunity after infection or immunization requires physical
      interactions within a lymph node (LN) T-zone between antigen-bearing dendritic
      cells (DCs) that arrive from peripheral tissues and rare cognate T cells entering
      via high endothelial venules (HEVs). This interaction results in activation of
      cognate T cells, expansion of that T cell lineage and their exit from the LN T
      zone via efferent lymphatics (ELs). How antigen-specific T cells locate DCs
      within this complex environment is controversial, and both random T cell
      migration and chemotaxis have been proposed. We developed an agent-based
      computational model of a LN that captures many features of T cell and DC dynamics
      observed by two-photon microscopy. Our simulations matched in vivo two-photon
      microscopy data regarding T cell speed, short-term directional persistence of
      motion and cell motility. We also obtained in vivo data regarding density of T
      cells and DCs within a LN and matched our model environment to measurements of
      the distance from HEVs to ELs. We used our model to compare chemotaxis with
      random motion and showed that chemotaxis increased total number of T cell DC
      contacts, but decreased unique contacts, producing fewer activated T cells. Our
      results suggest that, within a LN T-zone, a random search strategy is optimal for
      a rare cognate T cell to find its DC match and maximize production of activated T
      cells.

PMID- 18068195
TI  - Enhanced sterol response element-binding protein in postintervention restenotic
      blood vessels plays an important role in vascular smooth muscle proliferation.
AB  - Postintervention restenosis (PIRS) after balloon angioplasty or stent
      implantation is a limitation for these interventional procedures even with the
      advent of new drug-eluting stents. Sterol regulatory element-binding proteins
      (SREBP) are transcription factors governing cellular lipid biosynthesis and thus
      critical in the regulation of the lipid-rich cell membranes. PIRS following
      injury results partially from newly proliferating cells expressing vascular
      smooth muscle cell (VSMC) markers. Platelet-derived growth factor (PDGF),
      lysophosphatidic acid (LPA) and alpha(1)-adrenergic receptor stimulation are well
      recognized diverse mitogens for VSMC activation in PIRS. We examined whether
      PDGF, LPA and alpha(1)-adrenergic receptor stimulation with phenylephrine (PE)
      regulate SREBP expression and subsequently, VSMC proliferation. Our results show
      that PDGF, LPA and PE upregulate SREBP-1 in a time- and dose-dependent manner.
      PDGF, LPA and PE-mediated proliferation is dependent on SREBP since inhibition of
      SREBP expression using targeted knockdown of the SREBP precursor SREBP activating
      protein (SCAP) by siRNA led to an attenuation of SREBP expression and decreased
      PDGF, LPA and PE induced proliferation. In two different in vivo PIRS models we
      found that SREBP-1 was enhanced in the injured blood vessel wall, especially
      within the neointima and co-localized with alpha-smooth muscle actin positive
      cells. Thus, SREBP is enhanced in the vessel wall following PIRS and is important
      in the regulation of pro-hyperplasia molecular signaling. SREBP inhibition may be
      a powerful tool to limit PIRS.

PMID- 18068196
TI  - Nitric oxide mediates cardiac protection of tissue kallikrein by reducing
      inflammation and ventricular remodeling after myocardial ischemia/reperfusion.
AB  - We assessed the role of nitric oxide (NO) and the kinin B2 receptor in mediating
      tissue kallikrein's actions in intramyocardial inflammation and cardiac
      remodeling after ischemia/reperfusion (I/R) injury. Adenovirus carrying the human
      tissue kallikrein gene was delivered locally into rat hearts 4 days prior to 30
      minute ischemia followed by 24-hour or 7-day reperfusion with or without
      administration of icatibant, a kinin B2 receptor antagonist, or N(omega)-nitro-L
      arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. Kallikrein
      gene delivery improved cardiac contractility and diastolic function, reduced
      infarct size at 1 day after I/R without affecting mean arterial pressure.
      Kallikrein treatment reduced macrophage/monocyte and neutrophil accumulation in
      the infarcted myocardium in association with reduced intercellular adhesion
      molecule-1 levels. Kallikrein increased cardiac endothelial nitric oxide synthase
      phosphorylation and NO levels and decreased superoxide formation, TGF-beta1
      levels and Smad2 phosphorylation. Furthermore, kallikrein reduced I/R-induced
      JNK, p38MAPK, IkappaB-alpha phosphorylation and nuclear NF-kappaB activation. In
      addition, kallikrein improved cardiac performance, reduced infarct size and
      prevented ventricular wall thinning at 7 days after I/R. The effects of
      kallikrein on cardiac function, inflammation and signaling mediators were all
      blocked by icatibant and L-NAME. These results indicate that tissue kallikrein
      through kinin B2 receptor and NO formation improves cardiac function, prevents
      inflammation and limits left ventricular remodeling after myocardial I/R by
      suppression of oxidative stress, TGF-beta1/Smad2 and JNK/p38MAPK signaling
      pathways and NF-kappaB activation.

PMID- 18068197
TI  - Riluzole-induced block of voltage-gated Na+ current and activation of BKCa
      channels in cultured differentiated human skeletal muscle cells.
AB  - Riluzole is known to be of therapeutic use in the management of amyotrophic
      lateral sclerosis. In this study, we investigated the effects of riluzole on ion
      currents in cultured differentiated human skeletal muscle cells (dHSkMCs).
      Western blotting revealed the protein expression of alpha-subunits for both large
      conductance Ca2+-activated K+ (BK(Ca)) channel and Na+ channel (Na(v)1.5) in
      these cells. Riluzole could reduce the frequency of spontaneous beating in
      dHSkMCs. In whole-cell configuration, riluzole suppressed voltage-gated Na+
      current (I(Na)) in a concentration-dependent manner with an IC50 value of 2.3
      microM. Riluzole (10 microM) also effectively increased Ca2+-activated K+ current
      (I(K(Ca))) which could be reversed by iberiotoxin (200 nM) and paxilline (1
      microM), but not by apamin (200 nM). In inside-out patches, when applied to the
      inside of the cell membrane, riluzole (10 microM) increased BK(Ca)-channel
      activity with a decrease in mean closed time. Simulation studies also unraveled
      that both decreased conductance of I(Na) and increased conductance of I(K(Ca))
      utilized to mimic riluzole actions in skeletal muscle cells could combine to
      decrease the amplitude of action potentials and increase the repolarization of
      action potentials. Taken together, inhibition of I(Na) and stimulation of BK(Ca)
      channel activity caused by this drug are partly, if not entirely, responsible for
      its muscle relaxant actions in clinical setting.

PMID- 18068198
TI  - Modelling the effect of urbanization on the transmission of an infectious
      disease.
AB  - This paper models the impact of urbanization on infectious disease transmission
      by integrating a CA land use development model, population projection matrix
      model and CA epidemic model in S-Plus. The innovative feature of this model lies
      in both its explicit treatment of spatial land use development, demographic
      changes, infectious disease transmission and their combination in a dynamic,
      stochastic model. Heuristically-defined transition rules in cellular automata
      (CA) were used to capture the processes of both land use development with urban
      sprawl and infectious disease transmission. A population surface model and
      dwelling distribution surface were used to bridge the gap between urbanization
      and infectious disease transmission. A case study is presented involving
      modelling influenza transmission in Southampton, a dynamically evolving city in
      the UK. The simulation results for Southampton over a 30-year period show that
      the pattern of the average number of infection cases per day can depend on land
      use and demographic changes. The modelling framework presents a useful tool that
      may be of use in planning applications.

PMID- 18068199
TI  - Multistationarity in the activation of a MAPK: parametrizing the relevant region
      in parameter space.
AB  - Mathematical models of biochemical reaction networks in the form of ordinary
      differential equations can exhibit all sorts of complex dynamical behaviour. It
      is for example known, that even a single layer of a MAPK cascade can exhibit
      bistability (i.e. there exist multiple (positive) steady state solutions). It is
      almost a common-place that bistability or some other form of multistationarity
      are observed in many biochemical reaction networks, especially if the focus is on
      signal transduction or cell cycle regulation. However, multistationarity is only
      exhibited if the parameter vector is located in an appropriate region of
      parameter space. To find these regions, for example by using numerical tools like
      bifurcation analysis, is a non-trivial task as it amounts to searching the whole
      parameter space. In this paper we show that for a model of a single layer of a
      MAPK cascade it is possible to derive analytical descriptions of these regions,
      if mass action kinetics are used. Moreover, our results give rise to a
      straightforward explanation for the 'robust yet fragile' behaviour in the
      activation of a MAPK.

PMID- 18068200
TI  - 7-Ketocholesterol activates caspases-3/7, -8, and -12 in human microvascular
      endothelial cells in vitro.
AB  - 7-Ketocholesterol (7kCh) is a major oxysterol found associated with vascular
      diseases. Human microvascular endothelial cells (HMVECs) were cultured with
      different concentrations of 7kCh with and without inhibitors. Cell viabilities
      and caspase activities were assessed. 7kCh caused loss of cell viability in a
      dose-dependent manner. Caspases-8, -12, and -3/7 but not caspase-9 were activated
      by 7kCh treatment. The 7kCh-induced caspase-8 activity was blocked partially by
      pre-treatment with z-VAD-fmk and z-IETD-fmk, a caspase-8 inhibitor. However, pre
      treatment with z-ATAD-fmk, a caspase-12 inhibitor, followed by 7kCh exposure lead
      to significantly increased caspase-8 activity. This suggests that caspase-8 and
      caspase-12 pathways have unique inhibition patterns and that caspase-12 is likely
      not upstream and feeding into caspase-8 but the pathways may function in parallel
      to each other. Caspase-3/7 activation was inhibited partially by low density
      lipoprotein (LDL), high density lipoprotein (HDL), z-VAD-fmk (pan-caspase
      inhibitor), and low doses (0.01 and 0.001 microM) of the cholesterol lowering
      drug, simvastatin. However, only LDL partially protected against 7kCh-induced
      loss of cell viability suggesting that caspase-independent pathways also
      contributed to the cell loss and that protection from oxysterol damage may
      require inhibition of multiple pathways. Moreover, our data suggest that
      oxysterols such as 7kCh can damage HMVECs cells in part via caspase-dependent
      apoptosis and may play a role in vascular and retinal diseases.

PMID- 18068201
TI  - Interactions of blood cell constituents: experimental investigation and
      computational modeling by discrete particle dynamics algorithm.
AB  - When the size of individual blood constituents [e.g., red blood cells (RBCs),
      white blood cells, platelets] becomes comparable to the size of blood vessels,
      the interactions among blood constituents in determining the blood behavior can
      no longer be ignored. In this paper, we have developed a comprehensive
      computational model to simulate the motion of an individual platelet in the
      plasma medium and its binding to the microvessel wall. The model is based on a
      Discrete Particle Dynamics (DPD) algorithm, in which blood plasma, platelets and
      the vessel walls are treated as a group of discretized mesoscopic size particles
      interacting through conservative, dissipative and random forces. Deposition
      (i.e., binding) of platelets is modeled by considering attractive forces at the
      vessel wall, which is characterized by the values of the effective spring
      constant for platelet adhesion. To test this model, we simulated platelet
      deposition in a perfusion chamber. By matching the simulation results to
      experimental data, the effective platelet spring constants were determined and
      were found to be approximately 50 N/m, which is within a physiologically relevant
      range. It is demonstrated that the DPD analysis offers the capability of
      simulating the time-dependent binding of platelets. We conclude that this model
      provides a new approach for studying the interaction among blood constituents.

PMID- 18068202
TI  - Molecular characterization of microbial mutations induced by ion beam
      irradiation.
AB  - A positive selection system for gene disruption using a sucrose-sensitive
      transgenic rhizobium was established and used for the molecular characterization
      of mutations induced by ion beam irradiations. Single nucleotide substitutions,
      insertions, and deletions were found to occur in the sucrose sensitivity gene,
      sacB, when the reporter line was irradiated with highly accelerated carbon and
      iron ion beams. In all of the insertion lines, fragments of essentially the same
      sequence and of approximately 1188bp in size were identified in the sacB regions.
      In the deletion lines, iron ions showed a tendency to induce larger deletions
      than carbon ions, suggesting that higher LET beams cause larger deletions. We
      found also that ion beams, particularly "heavier" ion beams, can produce single
      gene disruptions and may present an effective alternative to transgenic
      approaches.

PMID- 18068203
TI  - Physical activity, fat intake and body fat.
AB  - The body fatness of a subject is a long-term reflection of the energy balance,
      the more intake exceeds expenditure the more energy is stored as fat. There is
      not yet a clear answer on the question whether the current obesity epidemic is a
      consequence of gluttony or sloth. Review studies do not show a reduction of
      physical activity over the years, and food intake is difficult to measure in
      daily life conditions. Food intake can only be derived from self-report, where
      under-reporting of food intake and selective underreporting of fat intake are
      major issues. Fat intake might be an important factor in the increase of body
      weight. Many studies suggest the capacity of the body to oxidize dietary fat is a
      major risk factor for a positive energy balance. Additionally, there is evidence
      that most of the fat consumed is stored before oxidation. Obesity prone subjects
      might be characterized by a higher storage of dietary fat. The only way to
      increase the oxidation of dietary fat, other than consuming more dietary fat, is
      to increase energy expenditure by an increase of physical activity. Indeed, there
      are indications that physical activity is an important determinant of fat
      oxidation. Based on the evidence presented, it is concluded that the obesity
      epidemic is mainly due to a high dietary intake, especially as fat, and that
      physical activity can be a tool to modulate the effect of fat intake on body fat.

PMID- 18068204
TI  - Caffeine and related purine alkaloids: biosynthesis, catabolism, function and
      genetic engineering.
AB  - Details of the recently elucidated biosynthetic pathways of caffeine and related
      purine alkaloids are reviewed. The main caffeine biosynthetic pathway is a
      sequence consisting of xanthosine-->7-methylxanthosine-->7-methylxanthine-
      >theobromine-->caffeine. Genes encoding N-methyltransferases involved in three of
      these four reactions have been isolated and the molecular structure of N
      methyltransferases investigated. Pathways for the catabolism of caffeine have
      also been studied, although there are currently no reports of enzymatic and
      genetic studies having been successfully carried out. Metabolism of purine
      alkaloids in species including Camellia, Coffea, Theobroma and Ilex plants is
      summarised, and evidence for the involvement of caffeine in chemical defense and
      allelopathy is discussed. Finally, information is presented on metabolic
      engineering that has produced coffee seedlings with reduced caffeine content, and
      transgenic caffeine-producing tobacco plants with enhanced disease resistance.

PMID- 18068205
TI  - HIV-1 resistance to the anti-HIV activity of a shRNA targeting a dual-coding
      region.
AB  - We generated a lymphoid cell line (Sup-T1-Rev/Env) that stably expresses a 19-bp
      short hairpin RNA (shRNA) targeting a conserved region of HIV-1 encoding for the
      Envelope and Rev proteins, which potently inhibited viral replication. However,
      continuous passage of HIV-1 in Sup-T1-Rev/Env generated virus mutants able to
      overcome the RNAi restriction. Sequence analysis of the emerging viruses showed
      that mutations were located at positions 5 and 17 of the target sequence. Both
      mutations are silent in the Env frame, but the mutation 5 generated an amino acid
      change (V47M) in the Rev reading frame. We have analyzed the impact of these two
      mutations on the RNAi mechanism, showing a more crucial role of the mutation 17
      in the resistance to RNAi. We show that even targeting a conserved region of the
      HIV-1 genome involved in the biosynthesis of two essential genes, env and rev,
      the virus could evolve to escape by single point mutations in the target
      sequence, without a significant fitness cost.

PMID- 18068206
TI  - Environmental implications of soil remediation using the Fenton process.
AB  - This work evaluates some collateral effects caused by the application of the
      Fenton process to 1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane (DDT) and diesel
      degradation in soil. While about 80% of the diesel and 75% of the DDT present in
      the soil were degraded in a slurry system, the dissolved organic carbon (DOC) in
      the slurry filtrate increased from 80 to 880mgl(-1) after 64h of reaction and the
      DDT concentration increased from 12 to 50microgl(-1). Experiments of diesel
      degradation conducted on silica evidenced that soluble compounds were also formed
      during diesel oxidation. Furthermore, significant increase in metal
      concentrations was also observed in the slurry filtrate after the Fenton
      treatment when compared to the control experiment leading to excessive
      concentrations of Cr, Ni, Cu and Mn according to the limits imposed for water.
      Moreover, 80% of the organic matter naturally present in the soil was degraded
      and a drastic volatilization of DDT and 2,2-bis(4-chlorophenyl)-1,1
      dichloroethylene was observed. Despite the high percentages of diesel and DDT
      degradation in soil, the potential overall benefits of its application must be
      evaluated beforehand taking into account the metal and target compounds
      dissolution and the volatilization of contaminants when the process is applied.

PMID- 18068207
TI  - Compressed air-assisted solvent extraction (CASX) for metal removal.
AB  - A novel process, compressed air-assisted solvent extraction (CASX), was developed
      to generate micro-sized solvent-coated air bubbles (MSAB) for metal extraction.
      Through pressurization of solvent with compressed air followed by releasing air
      oversaturated solvent into metal-containing wastewater, MSAB were generated
      instantaneously. The enormous surface area of MSAB makes extraction process
      extremely fast and achieves very high aqueous/solvent weight ratio (A/S ratio).
      CASX process completely removed Cr(VI) from acidic electroplating wastewater
      under A/S ratio of 115 and extraction time of less than 10s. When synthetic
      wastewater containing Cd(II) of 50mgl(-1) was treated, A/S ratios of higher than
      714 and 1190 could be achieved using solvent with extractant/diluent weight ratio
      of 1:1 and 5:1, respectively. Also, MSAB have very different physical properties,
      such as size and density, compared to the emulsified solvent droplets, making
      separation and recovery of solvent from treated effluent very easy.

PMID- 18068208
TI  - The influence of Sarcocornia fruticosa on retention of PAHs in salt marsh
      sediments (Sado estuary, Portugal).
AB  - Depth concentration profiles of PAHs, organic carbon and dissolved oxygen in non
      colonised sediments and sediments colonised by Sarcocornia fruticosa from Mitrena
      salt marsh (Sado, Portugal) were determined in November 2004 and April 2005.
      Belowground biomass and PAH levels in below and aboveground material were also
      determined. In both periods, colonised sediments were oxygenated until 15-cm,
      rich in organic carbon (max 4.4%) and presented much higher PAH concentrations
      (max. 7.1 microg g(-1)) than non-colonised sediments (max. 0.55 microg g(-1)).
      Rooting sediments contained the highest PAH concentrations. The five- and six
      ring compounds accounted to 50-75% of the total PAHs in colonised sediments,
      while only to 30% in non-colonised sediments. The elevated concentrations of PAHs
      in colonised sediments may be attributed to the transfer of dissolved PAH
      compounds towards the roots as plant uptake water and subsequent sequestration
      onto organically rich particles. A phase-partitioning mechanism probably explains
      the higher retention of the heavier PAHs. In addition oxygenated conditions of
      the rooting sediments favour the degradation of the lighter PAHs and explain the
      elevated proportion of the heavier compounds. Below and aboveground materials
      presented lower PAH concentrations (0.18-0.38 microg g(-1)) than colonised
      sediments. Only 3- and 4-PAHs were quantified in aboveground material, reflecting
      either preferential translocation of lighter compounds from roots or atmospheric
      deposition.

PMID- 18068209
TI  - Atmospheric concentrations and phase partitioning of polybrominated diphenyl
      ethers (PBDEs) in Izmir, Turkey.
AB  - Atmospheric concentrations of 7 PBDE congeners (BDE-28, -47, -99, -100, -153, 
      154 and -209) were determined at four sites (i.e. Suburban, Urban 1, Urban 2,
      Industrial) in Izmir, Turkey and their gas/particle partitioning was
      investigated. Total PBDE ( summation operator(7)PBDE) concentrations ranged
      between 11 (Urban 1) and 149pgm(-3) (Industrial) in summer, while in winter, they
      ranged from 6 (Suburban) to 81pgm(-3) (Industrial). BDE-209 was the dominant
      congener at all sites, followed by BDE-99 and -47. Investigation of source
      profiles indicated that the air samples were dominated by congeners of the penta
      and deca-technical BDE mixtures. The measured PBDE particle fractions were
      compared to the predictions of the K(OA) (octanol-air partition coefficient)
      based equilibrium partitioning model and to the dynamic uptake model developed by
      others for passive samplers, which was adapted to model gas-particle partitioning
      in this study. For BDE-28, good agreement was observed between the experimental
      particle fractions and those predicted by the equilibrium partitioning model.
      However, this model overestimated the particle fractions of other congeners. The
      predictions of the dynamic uptake model supported the hypothesis that the
      unexpectedly high partitioning of BDEs (except BDE-28) to the gas-phase is due to
      their departure from equilibrium partitioning. When congeners with very large
      octanol-air partition coefficients (i.e. BDE-100, -99, -154, -153, and -209) are
      emitted from their sources in the gas-phase, they may remain in that phase for
      several months before reaching equilibrium with atmospheric particles. This may
      also have important implications for the transport of atmospheric PBDEs. For
      example, in addition to particle-bound transport, the gas-phase transport of
      highly brominated congeners (i.e. BDE-209) may also be important.

PMID- 18068210
TI  - Effect of sewage sludges contaminated with polybrominated diphenylethers on
      agricultural soils.
AB  - The fate of polybrominated diphenyl ethers (PBDEs) in sewage sludge after
      agricultural application was analysed. This study was based on the analysis of
      sewage sludge and sludge amended soil samples collected during 2005. PBDE
      concentrations in sewage sludge ranged from 197 to 1185ng/g dry weight (dw),
      being deca-BDE-209 the predominant congener. PBDE levels in soils ranged between
      21 and 690ng/g dw, being BDE-209 also the predominant congener in all soil
      samples. Sewage-sludge amendment at the research stations increased
      concentrations of all BDE congeners 1.2- to 45-fold, with the highest increases
      for BDE-209. Results obtained evidenced the cumulative effect of the sludge
      application rates. Moreover, high levels found at soils four years after the last
      sludge application indicate persistence of PBDEs in soils, including deca-BDE
      209.

PMID- 18068211
TI  - Greenhouse gas emissions from municipal solid waste management in Indian mega
      cities: a case study of Chennai landfill sites.
AB  - Municipal solid waste generation rate is over-riding the population growth rate
      in all mega-cities in India. Greenhouse gas emission inventory from landfills of
      Chennai has been generated by measuring the site specific emission factors in
      conjunction with relevant activity data as well as using the IPCC methodologies
      for CH4 inventory preparation. In Chennai, emission flux ranged from 1.0 to
      23.5mg CH4m(-2)h(-1), 6 to 460microg N2Om(-2)h(-1) and 39 to 906mg CO2m(2)h(-1)
      at Kodungaiyur and 0.9 to 433mg CH4m(-2)h(-1), 2.7 to 1200microg N2Om(-2)h(-1)
      and 12.3 to 964.4mg CO2m(-2)h(-1) at Perungudi. CH4 emission estimates were found
      to be about 0.12Gg in Chennai from municipal solid waste management for the year
      2000 which is lower than the value computed using IPCC, 1996 [IPCC, 1996. Report
      of the 12th session of the intergovernmental panel of climate change, Mexico
      City, 1996] methodologies.

PMID- 18068212
TI  - Ozonation of oil sands process water removes naphthenic acids and toxicity.
AB  - Naphthenic acids are naturally-occurring, aliphatic or alicyclic carboxylic acids
      found in petroleum. Water used to extract bitumen from the Athabasca oil sands
      becomes toxic to various organisms due to the presence of naphthenic acids
      released from the bitumen. Natural biodegradation was expected to be the most
      cost-effective method for reducing the toxicity of the oil sands process water
      (OSPW). However, naphthenic acids are poorly biodegraded in the holding ponds
      located on properties leased by the oil sands companies. In the present study,
      chemical oxidation using ozone was investigated as an option for mitigation of
      this toxicity. Ozonation of sediment-free OSPW was conducted using proprietary
      technology manufactured by Seair Diffusion Systems Inc. Ozonation for 50min
      generated a non-toxic effluent (based on the Microtox bioassay) and decreased the
      naphthenic acids concentration by approximately 70%. After 130min of ozonation,
      the residual naphthenic acids concentration was 2mgl(-1): <5% of the initial
      concentration in the filtered OSPW. Total organic carbon did not change with
      130min of ozonation, whereas chemical oxygen demand decreased by approximately
      50% and 5-d biochemical oxygen demand increased from an initial value of 2mgl(-1)
      to a final value of 15mgl(-1). GC-MS analysis showed that ozonation resulted in
      an overall decrease in the proportion of high molecular weight naphthenic acids
      (n> or = 22).

PMID- 18068213
TI  - New hand bones of Hadropithecus stenognathus: implications for the paleobiology
      of the Archaeolemuridae.
AB  - A partial, associated skeleton of Hadropithecus stenognathus (AHA-I) was
      discovered in 2003 at Andrahomana Cave in southeastern Madagascar. Among the
      postcranial elements found were the first hand bones (right scaphoid, right
      hamate, left first metacarpal, and right and left fifth metacarpals) attributed
      to this rare subfossil lemur. These hand bones were compared to those of extant
      strepsirrhines and catarrhines in order to infer the positional adaptations of
      Hadropithecus, and they were compared to those of Archaeolemur in order to assess
      variation in hand morphology among archaeolemurids. The scaphoid tubercle does
      not project palmarly as in suspensory and climbing taxa, and the hamate has no
      hook at all (just a small tubercle), which also points to a poorly developed
      carpal tunnel. There is a distinctive, radioulnarly directed "spiral" facet for
      articulation with the triquetrum that is most similar in orientation to that of
      more terrestrial primates (i.e., Lemur catta, Papio, and Gorilla). The first
      metacarpal is very reduced and represents only 48% of the length of metacarpal V,
      as in Archaeolemur, which suggests that pollical grasping of arboreal supports
      was not important. Compared to Archaeolemur, the shaft of metacarpal V is
      gracile, and the head has no dorsal ridge and lacks characteristics functionally
      associated with digitigrade, extended metacarpophalangeal joint postures.
      Proximally, the articular facet for the hamate is oriented more dorsally. Thus,
      the carpometacarpal joint V appears to have a distinctive hyperextended set,
      which has no analog among living or extinct primates. The carpals of
      Hadropithecus are diagnostic of a pronograde, arboreal and terrestrial (although
      not digitigrade) locomotor repertoire that typifies Lemur catta and some Old
      World monkeys. No clinging, suspensory, or climbing specializations that
      characterize indriids or lorises can be found in the hand of this subfossil
      lemur. The hand of Hadropithecus likely had similar ranges of movement at the
      radiocarpal and midcarpal joints as of those of pronograde primates, such as
      lemurids, for which the hand is held in a more extended, pronated, and neutral
      (i.e., showing less ulnar deviation) position during locomotion in comparison to
      that of vertical clingers or slow climbers. Although highly autapomorphic, the
      hand of Hadropithecus resembles that of its sister taxon, Archaeolemur, in having
      a very reduced pollex and an articular facet on the scaphoid for a sizeable
      prepollex. These unusual hand features reinforce the monophyly of the
      Archaeolemuridae.

PMID- 18068214
TI  - Life history costs and benefits of encephalization: a comparative test using data
      from long-term studies of primates in the wild.
AB  - The correlation between brain size and life history has been investigated in many
      previous studies, and several viable explanations have been proposed. However,
      the results of these studies are often at odds, causing uncertainties about
      whether these two character complexes underwent correlated evolution. These
      disparities could arise from the mixture of wild and captive values in the
      datasets, potentially obscuring real relationships, and from differences in the
      methods of controlling for phylogenetic non independence of species values. This
      paper seeks to resolve these difficulties by (1) proposing an overarching
      hypothesis that encompasses many of the previously proposed hypotheses, and (2)
      testing the predictions of this hypothesis using rigorously compiled data and
      utilizing multiple methods of analysis. We hypothesize that the adaptive benefit
      of increased encephalization is an increase in reproductive lifespan or
      efficiency, which must be sufficient to outweigh the costs due to growing and
      maturing the larger brain. These costs and benefits are directly reflected in the
      length of life history stages. We tested this hypothesis on a wide range of
      primate species. Our results demonstrate that encephalization is significantly
      correlated with prolongation of all stages of developmental life history except
      the lactational period, and is significantly correlated with an extension of the
      reproductive lifespan. These results support the contention that the link between
      brain size and life history is caused by a balance between the costs of growing a
      brain and the survival benefits the brain provides. Thus, our results suggest
      that the evolution of prolonged life history during human evolution is caused by
      increased encephalization.

PMID- 18068215
TI  - Paranasal pneumatization in extant and fossil Cercopithecoidea.
AB  - Unlike most primates, extant cercopithecoids lack maxillary sinuses, which are
      pneumatic spaces in the facial skeleton lateral of the nasal cavity proper.
      Character state analysis of living cercopithecoids across well-supported
      topologies suggests that the sinus was lost at the origin of the superfamily,
      only to have evolved again convergently in extant macaques. Recent work has shown
      that a) the 'early loss' hypothesis is supported by the lack of any
      pneumatization in Victoriapithecus, a stem cercopithecoid, b) like extant
      macaques, the fossil cercopithecine Paradolichopithecus shows evidence of
      presence of the maxillary sinus (MS), and c) unlike extant colobines, the fossil
      colobine Libypithecus also possesses a maxillary sinus. To more fully assess the
      pattern of cercopithecoid sinus evolution, fossil taxa from both subfamilies
      (Colobinae, Cercopithecinae) were examined both visually and by computed
      tomography (CT). The observations were evaluated according to standard anatomical
      criteria for defining sinus spaces, and compared with data from all extant Old
      World monkey genera. Most taxa examined conformed to the pattern already
      discerned from extant cercopithecoids. Maxillary sinus absence in Theropithecus
      oswaldi, Mesopithecus, and Rhinocolobus is typical for all extant cercopithecids
      except Macaca. The fossil macaque Macaca majori possesses a well-developed
      maxillary sinus, as do all living species of the genus. Cercopithecoides, on the
      other hand, differs from all extant colobines in possessing a maxillary sinus.
      Thus, paranasal pneumatization has reemerged a minimum of two and possibly three
      times in cercopithecoids. The results suggest that maxillary sinus absence in
      cercopithecoids is due to suppression, rather than complete loss.

PMID- 18068216
TI  - Utilizing geochemical, hydrologic, and boron isotopic data to assess the success
      of a salinity and selenium remediation project, Upper Colorado River Basin, Utah.
AB  - Stream discharge and geochemical data were collected at two sites along lower
      Ashley Creek, Utah, from 1999 to 2003, to assess the success of a site specific
      salinity and Se remediation project. The remediation project involved the
      replacement of a leaking sewage lagoon system that was interacting with Mancos
      Shale and increasing the dissolved salinity and Se load in Ashley Creek.
      Regression modeling successfully simulated the mean daily dissolved salinity and
      Se loads (R(2) values ranging from 0.82 to 0.97) at both the upstream (AC1) and
      downstream (AC2/AC2A) sites during the study period. Prior to lagoon closure, net
      gain in dissolved-salinity load exceeded 2177 metric tons/month and decreased
      after remediation to less than 590 metric tons/month. The net gain in dissolved
      Se load during the same pre-closure period exceeded 120 kg/month and decreased to
      less than 18 kg/month. Sen's slope estimator verified the statistical
      significance of the modeled reduction in monthly salinity and Se loads. Measured
      gain in dissolved constituent loads during seepage tests conducted during
      September and November 2003 ranged from 0.334 to 0.362 kg/day for dissolved Se
      and 16.9 to 26.1 metric tons/day for dissolved salinity. Stream discharge and
      changes in the isotopic values of delta boron-11 (delta(11)B) were used in a
      mixing model to differentiate between constituent loadings contributed by
      residual sewage effluent and naturally occurring ground-water seepage entering
      Ashley Creek. The majority of the modeled delta(11)B values of ground-water
      seepage were positive, indicative of minimal seepage contributions from sewage
      effluent. The stream reach between sites S3 and AC2A contained a modeled ground
      water seepage delta(11)B value of -2.4 per thousand, indicative of ground-water
      seepage composed of remnant water still draining from the abandoned sewage
      lagoons.

PMID- 18068217
TI  - Management of suspected pulmonary embolism patients with low clinical and low V/Q
      probability.
AB  - OBJECTIVE: To assess whether guidelines for the management of suspected PE,
      recommending that ventilation/perfusion (V/Q) scintigraphy should be followed by
      other imaging in case of non-diagnostic result, and interpreted along with the
      clinical probability, are applied in daily practice. DESIGN: Two-year audit
      study. SETTING: Tertiary hospital in France. PARTICIPANTS: All patients referred
      to the nuclear medicine department for a suspected pulmonary embolism (PE), with
      a low clinical probability, a positive D-Dimer test, and a low V/Q scintigraphy.
      INTERVENTION: We reviewed medical records to collect data on further diagnostic
      strategy and therapeutic management. MAIN OUTCOME MEASURE: Thromboembolic risk
      during a three-month follow up in patients who did not undergo anticoagulation
      therapy on the basis of a negative diagnostic work up. RESULTS: Of the 456
      selected patients, PE was excluded on the basis of a low pretest probability and
      a low V/Q scintigraphy probability without further testing in 184 (group 1). In
      the other 272 patients (group 2), 4 venous thromboembolism (VTE) events were
      diagnosed by leg vein ultrasonography and/or computed tomography pulmonary
      angiography. In patients who did not receive anticoagulant treatment during
      follow up, one patient from group 1 (0.6%, 95% confidence interval 0.1 to 3.3)
      and two patients from group 2 (0.9%, 95% CI 0.2 to 3.2) had an acute venous
      thromboembolic event. CONCLUSION: Different attitudes are adopted by physicians
      in patients with a low clinical probability and a low V/Q scintigraphy
      probability, without impact on safety, as assessed by a non-significant
      difference in the three-month thromboembolic risks between these two groups.

PMID- 18068218
TI  - Histochemical mapping of glycoconjugates in the testis of the one humped camel
      (Camelus dromedarius) during rutting and non-rutting seasons.
AB  - In the present study, the distribution of various sugar residues in the
      testicular cells of sexually mature camels during rutting and non-rutting seasons
      was examined employing 10 fluorescein isothiocyanate- (FITC) conjugated lectins.
      Lectin labeling was restricted to the germ cell lines and interstitial Leydig
      cells, while the Sertoli cells remained completely unlabeled. Our results
      revealed the presence of mannose (labeled by lectins PSA, LCA), galactose
      (labeled by PNA), GalNAc (labeled by HPA), and GlcNAc (labeled by WGA) residues
      in the camel spermatogonia. However, spermatocytes were only labeled with mannose
      (PSA, LCA) and GlcNAc (WGA) binding lectins. Binding sites for PSA, LCA and WGA
      in spermatogonia and spermatocytes were only evident during the rutting season.
      Although spermatids were exclusively labeled with PNA in the non-rutting seasons,
      other lectins (PSA, GSA-I, WGA) additionally bound to camel spermatids during the
      rutting period. Leydig cells and basal lamina of the seminiferous tubules of
      camel testis were consistently labeled with the mannose- (PSA, LCA) and GlcNAc-
      (WGA) binding lectins in both seasons, while DBA-labeling was seen in the Leydig
      cells during rutting period only. In conclusion, the findings of the present
      study clearly indicate that the camel testis contains a wide range of
      glycoconjugates (bearing mannosyl, galactosyl and glucosyl residues), and they
      lack fucosyl residues, both in the active sexual period and in the non-breeding
      season. The topographical distribution of the sugar moieties in the camel testis
      may indicate that specific carbohydrate structures are required for
      spermatogenesis during periods of sexual activity.

PMID- 18068220
TI  - A comparative immunohistochemical study of endocrine cells in the digestive tract
      of two frugivorous bats: Artibeus cinerius and Sturnira lilium.
AB  - The purpose of the present study was to examine the serotonin (5
      hydroxytryptamine, 5-HT), gastrin (GAS), cholecystokinin (CCK) and glucagon
      (GLUC) endocrine cells in the gastrointestinal tract of frugivorous
      Phillostomidae bats, Sturnira lilium and Artibeus cinerius, to clarify the
      correlation between distribution of cell types and their relative frequency, with
      feeding habits. Five portions of the gastrointestinal tract--fundus, pilorus, and
      three parts of the intestine, I, II and III--were examined. Most of the
      immunoreactive cells in the stomach and intestine were of triangular, oval or
      piriform shape. Serotonin-immunoreactive cells were most commonly found in the S.
      lilium intestine I (66.6+/-9.9) and the A. cinerius intestine III (35+/-18).
      Gastrin-immunoreactive cells were the most abundant cell type in the pyloric
      glands of both species. They were more numerous in A. cinerius (126.9+/-27.4)
      than in S. lilium (75.8+/-1.8). CCK-immunoreactive cells were found in the
      alimentary tract epithelia at moderate frequencies in both species. GLUC
      immunoreactive cells were detected at very low or low frequencies. This study
      suggests that there is a correlation between endocrine cell distribution and
      frequency, and the feeding habits of the bats.

PMID- 18068219
TI  - Glial cells: old cells with new twists.
AB  - Based on their characteristics and function--migration, neural protection,
      proliferation, axonal guidance and trophic effects--glial cells may be regarded
      as probably the most versatile cells in our body. For many years, these cells
      were considered as simply support cells for neurons. Recently, it has been shown
      that they are more versatile than previously believed--as true stem cells in the
      nervous system--and are important players in neural function and development.
      There are several glial cell types in the nervous system: the two most abundant
      are oligodendrocytes in the central nervous system and Schwann cells in the
      peripheral nervous system. Although both of these cells are responsible for
      myelination, their developmental origins are quite different. Oligodendrocytes
      originate from small niche populations from different regions of the central
      nervous system, while Schwann cells develop from a stem cell population (the
      neural crest) that gives rise to many cell derivatives besides glia and which is
      a highly migratory group of cells.

PMID- 18068221
TI  - Differences in performance between Sprague-Dawley and Fischer 344 rats in
      positive reinforcement tasks.
AB  - This experimental investigation tested two different strains of rat, Sprague
      Dawley (SD) and Fischer 344 (F344), in their ability to learn lever pressing for
      food (autoshaping) or intracranial self-administration (ICSA) of
      dextroamphetamine (AMPH) into the nucleus accumbens (NAcc). Additionally, a
      unique method of intracranial drug delivery was utilized, via reverse dialysis,
      by the use of a microdiaylsis probe. The experiments revealed definite behavioral
      differences between SD and F344 animals. The autoshaping data indicated that SD
      rats, on average, acquired lever pressing for food in fewer training days than
      F344 rats. Also, the ICSA experiment revealed that SD rats self-administered AMPH
      at a 30 mug/mul concentration. Lever pressing was significantly greater in those
      SD rats receiving AMPH than in the F344 drug group. Furthermore, the F344 rats
      never acquired lever pressing for intra-NAcc delivery of AMPH under our testing
      regime. These data reveal differences in performance of positively reinforced
      operant tasks between the inbred F344 rats as compared to the outbred SD strain.

PMID- 18068222
TI  - Dynamics of motile-sperm subpopulation structure in boar ejaculates subjected to
      "in vitro" capacitation and further "in vitro" acrosome reaction.
AB  - Incubation of diluted boar sperm from fresh ejaculates in a previously
      established "in vitro" capacitation medium induced a significant, time-dependent
      increase in several mean parameters of sperm motility, such as curvilinear
      velocity (VCL), linear velocity (VSL), mean velocity (VAP), linearity coefficient
      (LIN), straightness coefficient (STR) and wobble coefficient (WOB). Furthermore,
      motile boar-sperm semen samples were structured in four definite subpopulations.
      Subpopulation 1 showed the lowest values of VCL, VSL and VAP and also low values
      of linearity. Subpopulation 2 showed the second lowest values of VCL and VAP and
      higher values of LIN and STR. Subpopulation 3 was characterized by high values of
      velocity and low values of linearity. Finally, Subpopulation 4 was characterized
      by high values of velocity and linearity. "In vitro" capacitation and further
      acrosome reaction induced changes in the motility characteristics of each
      subpopulation as well as in their percentage distribution, Subpopulations 3 and 4
      being those that showed the most significant changes. However, despite these
      changes, the observed, overall four-subpopulation structure was firmly maintained
      during the entire "in vitro" capacitation and acrosome-reaction process. Our
      results suggest that capacitation-induced motility changes are related to
      specific changes in the percentage of each motile-sperm subpopulation in the
      ejaculate without losing the overall, specific four-subpopulation structure. In
      this way, the maintenance of a four-subpopulation structure seems to be important
      in the control of the whole ejaculate physiology.

PMID- 18068223
TI  - Requirement for shrimp caspase in apoptosis against virus infection.
AB  - Caspases are central effectors in apoptosis. In this investigation, a novel
      caspase gene (designated as PjCaspase) obtained from the marine shrimp
      Marsupenaeus japonicus was found to be significantly upregulated in survivors of
      WSSV-challenged shrimp, suggesting that it might be involved in shrimp antiviral
      immunity. As revealed by RNAi assays, when the PjCaspase gene was silenced by
      gene-specific siRNA, the WSSV-induced apoptosis was significantly inhibited. The
      results showed that the PjCaspase gene was essential in the virus-induced
      apoptosis of shrimp. Based on the quantitative PCR detection, it was shown that
      the PjCaspase gene silencing resulted in the increase of virus copies, indicating
      that apoptosis played a key role in antiviral process of shrimp. As well known,
      caspase-3 and -8 are crucial caspases in apoptosis. The discovery of PjCaspase in
      this study would contribute another essential caspase involved in apoptosis
      against virus infection, which might reveal an ancient mechanism of caspase
      activation in invertebrate immunity against viruses.

PMID- 18068224
TI  - Macrophage migration inhibitory factor (MIF) is essential for development of
      zebrafish, Danio rerio.
AB  - Macrophage migration inhibitory factor (MIF) was discovered as the first cytokine
      that inhibited the random migration of macrophages. Recently, MIF has been
      reported to be involved in embryonic development in higher vertebrates. In fish,
      however, nothing is known about the function of MIF at early life stages,
      although immunological functions of MIF have been reported in adult fish. To
      elucidate the function of MIF during embryonic development in fish, we examined
      expression patterns and function of the zebrafish MIF gene using antisense
      morpholino-mediated knockdown (morpholino oligonucleotide-MO). In whole-mount in
      situ hybridization analysis, zebrafish MIF mRNA was detected in developing eyes,
      tectum, branchial arches, pectoral fin buds, liver and gut. The onset of MIF mRNA
      expression coincided with the beginning of tissue differentiation during
      embryogenesis. MIF-MO-injected embryos (morphants) displayed malformed eyes,
      abnormal swelling in the tectum and fourth ventricle region, and undeveloped jaw
      cartilage and pectoral fins. An increased number of apoptotic cells in the eye
      and neural tissues were observed in MIF morphants by histological analysis and
      acridine orange staining. Moreover, proliferating cell nuclear antigen (PCNA)
      positive cells were reduced in morphant eyes. These results suggest that MIF is
      essential for normal embryonic development even at the level of teleosts and that
      it functions as a growth factor for the proliferation and differentiation of
      embryonic tissues.

PMID- 18068225
TI  - The biological effects of rainbow trout (Oncorhynchus mykiss) recombinant
      interleukin-8.
AB  - In this report, recombinant interleukin-8 (rIL-8) was produced and its activity
      tested for the first time in fish. The rainbow trout rIL-8 was produced in
      Escherichia coli and purified using a 6xHis tag at the N-terminus. The rIL-8
      induced a dose-dependent migration of head kidney leukocytes at concentrations
      from 0.1 to 10 ng/ml, with a peak response at 1 ng/ml. Trout rIL-8 also had a
      significant effect on superoxide production by head kidney cells, with maximal
      activity at 0.1 and 1 ng/ml. When injected intraperitoneally into trout, rIL-8
      had a clear effect on total leukocyte number in the peritoneal cavity, with
      increasing doses (up to 5 microg) eliciting more cells. Of three leukocyte types
      distinguished, neutrophils were the dominant cell type, especially at higher rIL
      8 concentrations. In contrast, the proportion of macrophages and lymphocytes
      decreased with rIL-8 administration, suggesting that they were not attracted at
      the same rate as neutrophils.

PMID- 18068226
TI  - Environmental assessment of Norwegian priority pharmaceuticals based on the EMEA
      guideline.
AB  - An environmental risk assessment of eleven pharmaceuticals according to the
      guideline recommended by the European Medicines Evaluation Agency (EMEA) was
      performed. Cefuroxime, ciprofloxacin, cyclophosphamide, diclofenac,
      ethinylestradiol, ibuprofen, metoprolol, paracetamol, sulfamethoxazole,
      tetracycline and trimethoprim were selected for assessment by the Norwegian
      Pollution Control Authority. Predicted environmental concentrations (PECs) were
      calculated according to both the EMEA guideline and a conventional model for
      comparison and ranged from 0.0002 to 45 microg/L. Available acute and chronic
      toxicity data were collected from the literature, although no data were available
      for cyclophosphamide. Toxicity tests showed cyclophosphamide to have relatively
      low acute toxicity with an EC50 for Pseudokirchneriella subcapitata >100 mg/L and
      a Daphnia magna reproduction NOEC of 56 mg/L. These and the literature data were
      used to derive predicted no effect concentrations (PNEC). Risk quotients
      (PEC/PNEC) were then calculated for all 11 pharmaceutical compounds. Risk
      quotients greater than 1 were obtained for ciprofloxacin, diclofenac,
      ethinylestradiol, sulfamethoxazole and tetracycline according to the EMEA
      guideline. Measured environmental concentrations (MECs) confirmed that the
      release of ciprofloxacin from wastewater treatment works may potentially be of
      environmental concern in Norway.

PMID- 18068227
TI  - Arsenic cancer risk posed to human health from tilapia consumption in Taiwan.
AB  - Ingested inorganic arsenic is strongly associated with a wide spectrum of adverse
      health outcomes. We propose a bioaccumulation and the Weibull model-based
      epidemiological framework to accurately estimate the reference arsenic intake
      guideline for tilapia consumption and tilapia-cultured water arsenic
      concentration based on bioaccumulations of tilapia and gender/age/cancer-specific
      epidemiological data from the arseniasis-endemic area in Taiwan. Our results show
      a positive relationship between arsenic exposure and age/gender- and cancer
      specific cumulative incidence ratio using Weibull dose-response model. Based on
      male bladder cancer with an excess lifetime cancer risk of 10(-4), we estimate
      the reference tilapia inorganic arsenic guideline value to be 0.084 microg g(-1)
      dry wt based on the suggested daily consumption rate of 120 gd(-1). Our findings
      show that consumption of tilapia in a blackfoot disease (BFD)-endemic area poses
      no significant cancer risk (excess cancer risks ranging from 3.4 x 10(-5) to 9.3
      x 10(-5)), implying that people in BFD-endemic areas are not readily associated
      with higher fatalities for bladder cancer exposed from tilapia consumption. We
      are confident that our model can be easily adapted for other aquaculture species,
      and encourage risk managers to use the model to evaluate the potential population
      level long-term low-dose cancer risks. We conclude that, by integrating the
      bioaccumulation concept and epidemiological investigation of humans exposed to
      arsenic, we can provide a scientific basis for risk analysis to enhance risk
      management strategies.

PMID- 18068228
TI  - Modeling leaching behavior of solidified wastes using back-propagation neural
      networks.
AB  - In a previous study, treatment sludge obtained from a chemical industry, which
      contained potentially toxic heavy metals and organics, was characterized and
      solidified by solidification/stabilization (S/S). In this study, however, the
      prediction of leaching behavior of the sludge by linear regression method and
      neural networks (NNs) was discussed. NN analysis was used to construct models of
      leaching behavior as a function of mix composition (waste/binder ratio, W/B)
      using existing data from the previous study of cement-based S/S. The differences
      in leaching rate of each metal were also considered. The hazard characteristics
      of the waste were determined as defined in both Turkish and US EPA regulations,
      by means of Extraction Procedure Toxicity Test (EPTox) and DIN 38414-S4 Test. S/S
      studies were conducted using Portland cement to solidify the sludge containing
      high amount of Cr, Cu, Hg, Ni, Pb, and Zn. The W/B ratios of 36 specimens were
      kept between 0/100 and 40/100. The specimens were cured at room temperature for
      7, 28, and 90 days. The heavy metal content of the extracts of each specimen was
      detected usually less than standard concentrations in EPTox and DIN 38414-S4
      leaching procedures. By the use of NN, leaching behavior of the solidified wastes
      can be predicted and, therefore, optimum S/S technologies can be achieved.

PMID- 18068229
TI  - Comparative evaluation of oxidative stress status and manganese availability in
      plants growing on manganese mine.
AB  - This study pioneered an approach that determined the effects of excess manganese
      (Mn) on three species; Datura stramonium, Alhagi camelthorn and Chenopodium
      ambrosioides. We investigated their levels of Mn, antioxidative enzymes and
      oxidative damage biomarkers in plants (zone 1) in and outside (zone 2) the Mn
      mine. The results showed that total and available Mn were at toxic levels for
      plants growing on zone 1. The Mn levels in each plant species were higher in
      leaves, stems and roots. Mn was only accumulated significantly in leaf vacuoles
      of A. camelthorn. Antioxidative enzyme activities of C. ambrosioides and/or D.
      stramonium in zone 1 were higher in leaves, stems and then in their roots.
      Malondialdehyde (MDA) and dityrosine levels were insignificantly higher in
      tissues of the studied plants in zone 1 with respect to zone 2. The roots of
      studied plants showed significantly higher levels of these biomarkers in
      comparison with their leaves in zone 1. Accordingly, antioxidative enzymatic
      response to Mn-stress in D. stramonium and C. ambrosioides and possibly
      accumulation of Mn in leaf vacuoles of A. camelthorn, protected them from
      oxidative damages and involved in their tolerance in Mn mine.

PMID- 18068230
TI  - Aluminium induced oxidative stress and DNA damage in root cells of Allium cepa L.
AB  - Aluminium (Al) was evaluated for induction of oxidative stress and DNA damage
      employing the growing roots of Allium cepa L. as the assay system. Intact roots
      of A. cepa were treated with different concentrations, 0, 1, 10, 50, 100, or 200
      microM of aluminium chloride, at pH 4.5 for 4 h (or 2 h for comet assay) at room
      temperature, 25+/-1 degrees C. Following treatment the parameters investigated in
      root tissue were Al-uptake, cell death, extra cellular generation of reactive
      oxygen intermediates (ROI), viz. O(2)(*-), H(2)O(2) and (*)OH, lipid
      peroxidation, protein oxidation, activities of antioxidant enzymes namely
      catalase (CAT), superoxide dismutase (SOD), guaiacol peroxidase (GPX), ascorbate
      peroxidase (APX); and DNA damage, assessed by comet assay. The findings indicated
      that Al triggered generation of extra-cellular ROI following a dose-response.
      Through application of specific enzyme inhibitors it was demonstrated that extra
      cellular generation of ROI was primarily due to the activity of cell wall bound
      NADH-PX. Generation of ROI in root tissue as well as cell death was better
      correlated to the levels of root Al-uptake rather than to the concentrations of
      Al in ambient experimental solutions. Induction of lipid peroxidation and protein
      oxidation by Al were statistically significant. Whereas Al inhibited CAT
      activity, enhanced SOD, GPX and APX activities significantly; that followed dose
      response. Comet assay provided evidence that Al induced DNA damage in a range of
      concentrations 50-200 microM, which was comparable to that induced by
      ethylmethane sulfonate (EMS), an alkylating mutagen served as the positive
      control. The findings provided evidence that Al comparable to biotic stress
      induced oxidative burst at the cell surface through up- or down-regulation of
      some of the key enzymes of oxidative metabolism ultimately resulting in oxidative
      stress leading to DNA damage and cell death in root cells of A. cepa.

PMID- 18068231
TI  - Differential regulation of IKK alpha-mediated activation of IRF3/7 by NIK.
AB  - Type I interferons (IFNs) are critical mediators of the innate immune system to
      defend viral infection. Interferon regulatory factor (IRF) 3 and IRF7 are
      transcription factors that play critical roles in type I IFN production in
      response to viral infection. It has been shown that the protein kinase I kappaB
      kinase alpha (IKK alpha) is critically involved in IRF7 activation and IFN-alpha
      production in Toll-like receptor 7/9 (TLR7/9) signaling cascades. However,
      overexpression of IKK alpha does not activate the IFN-alpha promoters. Here we
      show that the protein kinase nuclear factor kappaB-inducing kinase (NIK) confers
      IKK alpha the ability to activate IRF3/7. Previous studies have shown that NIK
      phosphorylates IKK alpha at Ser-176 and Ser-180 residues, and mutation of each of
      the two residues to glutamate, which mimics its phosphorylation, caused
      constitutive activation of NF-kappaB. However, mutation of the two serine
      residues has differential effects on IKK alpha-mediated activation of IRF3/7.
      While IKK alpha(S176E) constitutively activates IRF3/7, IKK alpha(S180E) losses
      its ability to activate IRF3/7. These findings suggest that IKK alpha-mediated
      activation of NF-kappaB and IRF3/7 are differentially regulated by NIK, and NIK
      plays an important role in TLR7/9-mediated IFN-alpha production.

PMID- 18068232
TI  - Targeting microRNA expression to regulate angiogenesis.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the
      post-transcriptional level by either degradation or translational repression of a
      target mRNA. More than 400 miRNAs have been identified in the human genome, but
      the relevance of most of them to physiological and pathological processes remains
      unclear. Although downregulation of the miRNA-processing enzymes Dicer and Drosha
      is known to impair angiogenesis, only a few specific miRNAs targeting endothelial
      cell function and angiogenesis have been identified. miR-221 and miR-222 block
      endothelial cell migration, proliferation and angiogenesis in vitro by targeting
      the stem cell factor receptor c-Kit and indirectly regulating expression of
      endothelial nitric oxide synthase. A pro-angiogenic function has been established
      for the miR-17-92 cluster, which promotes tumor angiogenesis in vivo. Expression
      of let7-f and miR-27b contributes to in vitro angiogenesis. We review recent
      studies on the involvement of miRNA in angiogenesis and discuss their
      implications for miRNA-based therapeutic strategies targeting this process in
      disease.

PMID- 18068233
TI  - Development of a real-time quantitative reverse transcriptase PCR assay for
      detection of the Friend leukemia virus load in murine plasma.
AB  - Friend leukemia virus (FLV), a murine retrovirus, has been used as a model for
      elucidation of human immunodeficiency virus (HIV) immunopathogenesis and
      evaluation of anti-HIV drug effects for several decades. However, no method for
      direct detection of the plasma viral load has yet been reported. In this study, a
      TaqMan real-time quantitative reverse transcriptase PCR (qRT-PCR) assay was
      established for the rapid detection and quantitation of FLV. Measurement of the
      absolute FLV load was achieved through synthesis of a standard RNA from within
      the FLV envelope gene for generation of a standard curve. The assay allows
      quantitation over a range from 20 to 2 x 10(8) RNA copies per reaction in a two
      step real-time quantitative reverse transcriptase PCR protocol. The relationships
      between the initially injected FLV dose and the plasma FLV load and spleen index
      were explored. Following this, the in vivo effects of zidovudine, adefovir
      dipivoxil, and entecavir on mice infected with FLV were evaluated. The results
      showed that the plasma FLV load was not proportional to the spleen index over the
      same FLV injection dosage series, although a trend was observed. When evaluated
      using plasma viral load, high dose (15 mg/(kg d)) adefovir dipivoxil was capable
      of significant inhibition of FLV replication in mice. The qRT-PCR assay described
      here allows specific, sensitive and direct detection of FLV and may also provide
      more precise measurement of FLV load.

PMID- 18068234
TI  - In vivo effects of TGFbeta1 on the growth of gastric epithelium in suckling rats.
AB  - As the content of Transforming Growth Factor-beta (TGFbeta) wanes in the milk of
      lactating rat, an increase in TGFbeta is observed in the gastric epithelia
      concomitant with differentiation of the glands upon weaning. Whereas TGFbeta has
      been shown to inhibit the proliferation of gastrointestinal cells in vitro, its
      functional significance and mechanisms of action have not been studied in vivo.
      Therefore, we administered TGFbeta1 (1 ng/g body wt.) to 14-day-old rats in which
      the gastric epithelium was induced to proliferate by fasting, and determined the
      involvement of signaling through Smads and the impact on epithelial cell
      proliferation and apoptosis. After the gavage, we observed the progressive
      increase of active TGFbeta1 while TbetaRII-receptor remained constant in the
      gastric mucosa. By immunohistochemistry, we showed Smad2/3 increase at 60 min
      (p<0.05) and Smad2 phosphorylation/activation and translocation to the nucleus
      most prominently between 0 and 30 min after treatment (p<0.05). Importantly,
      TGFbeta1 inhibited cell proliferation (p<0.05), which was estimated by BrDU pulse
      labeling 12 h after gavage. Lower proliferation was reflected by increased
      p27(kip1) at 2 h (p<0.05). Also, TGFbeta1 increased apoptosis as measured by M30
      labeling at 60 and 180 min (p<0.001), and by morphological features at 12 h
      (p<0.05). In addition, we observed higher levels of activated caspase 3 (17 kDa)
      from 0 to 30 min. Altogether, these data indicate a direct effect of TGFbeta1
      signaling through Smads on both inhibiting proliferation, through alteration of
      cycle proteins, and inducing apoptosis of gastric epithelial cells in vivo.
      Further, the studies suggest a potential role for both milk and tissue-expressed
      TGFbeta1 in gastric growth during postnatal development.

PMID- 18068235
TI  - Idiopathic spontaneous coronary artery dissection. Clinical and pathological
      correlate.

PMID- 18068236
TI  - A rare cause of acute myocardial infarction: thrombotic thrombocytopenic purpura.

PMID- 18068237
TI  - A new method to reduce radiation exposure during multi-row detector cardiac
      computed tomographic angiography.
AB  - Unnecessary exposure to radiation is a major concern in cardiac computed
      tomographic angiography (CTA) and there have been several methods proposed to
      reduce radiation exposure in this imaging modality. One method that has not
      received much attention is the methodology of more precisely defining the upper
      and lower limits of the scan volume, as starting too high and/or going too low
      will proportionally add to the dose. We present our experience of performing CTA
      studies in our institution by better defining these scanning points.

PMID- 18068238
TI  - HIV and Long QT syndrome--cause or coincidence.
AB  - The Long QT syndrome is a disorder characterized by abnormalities of cardiac
      repolarisation, resulting in a propensity to polymorphic ventricular tachycardia
      (torsades de pointes) and sudden cardiac death. It remains unclear whether
      cardiac involvement with the HIV virus itself can cause QT prolongation. We
      report a case of a HIV infected young female presenting with recurrent syncope
      due to torsades de pointes.

PMID- 18068239
TI  - Is early anticoagulation necessary after biological aortic valve replacement?
AB  - Early antithrombotic therapy after biological aortic valve replacement (AVR) is
      controversial. The aim of this study was to determine the rate of thromboembolic
      events (TE) without anticoagulation treatment during the first 3 months after
      surgery. Out of 143 consecutive patients who underwent biological AVR from
      January 1998 to December 2004, 127 patients who did not receive anticoagulation
      were included (89%). Events during the first 3 months after surgery included: 2
      strokes (1.5%), 2 major bleedings (1.5%) and 9 deaths (7%) (none of them due to
      TE). In conclusion, the management of patients without antithrombotic treatment
      after biological AVR seems to be safe due to a low rate of TE.

PMID- 18068240
TI  - Standard measures of right ventricular function assessment in adult patients with
      acute sickle cell crises.
AB  - Chronic sickle cell (SC) disease is known to cause pulmonary hypertension (PH)
      which eventually affects right as well as left ventricular function. However, the
      acute effects of SC crisis on right ventricular (RV) function in adults have not
      been well described. Our echocardiography database was queried for patients
      followed in the outpatient hematology clinic, who were admitted with SC crises,
      and had an inpatient echocardiogram. Comparisons of RV fractional area change
      (RVFAC) and tricuspid annular peak systolic excursion (TAPSE) were then made to a
      group of healthy patients and a group with mild PH. TAPSE was normal in patients
      with SC disease (3.05+/-0.56). However, the SC patients had significantly larger
      RV's compared to controls and mild PH patients (31.33+/-7.23 cm(2) vs. 19.07+/
      4.49 cm(2) and 21.51+/-6.07 cm(2), respectively, P<0.0001). RVFAC was reduced in
      SC patients, and was comparable to patients with mild PH (46+/-9% vs. 49 +/-14%,
      P=0.4). We found no correlation between hemoglobin level (8.1+/-2.5 g) and RVFAC,
      TAPSE, or PH severity. We found that adult patients admitted with SC crises have
      frequent dilatation of the RV with an abnormal reduction in RVFAC, despite normal
      TAPSE values. Therefore, caution should be exercised in using TAPSE to estimate
      RV function in this patient population.

PMID- 18068241
TI  - Left ventricular non-compaction cardiomyopathy in children: Is segmental fibrosis
      the cause of tissue Doppler alterations and of EF reduction?
AB  - Noncompaction of the ventricular myocardium (LVNC) is a rare congenital
      cardiomyopathy resulting from an arrest in normal endomyocardial embryogenesis.
      In 2002 Jenni et al. [Jenni R, Wyss CA, Oechslin EN, Kaufmann PA. Isolated
      ventricular noncompaction is associated with coronary microcirculatory
      dysfunction. J Am Coll Cardiol 2002; 39:450-454.] reported a microvascular
      dysfunction in 12 patients affected by non compaction: areas of restricted
      myocardial perfusion have been documented by scintigraphy, suggesting a reduction
      of Coronary flow reserve. McMahon et al reported in a recent article a reduction
      of TD velocities in children with noncompaction of the left ventricle, compared
      with normal controls. The authors concluded their work saying that the reduction
      of lateral mitral Ea velocity helps to predict children with LVNC who are at risk
      of adverse clinical outcomes including death and need for cardiac
      transplantation. In a precedent report our group reported a strong correlation
      between pathological tissue Doppler and reduction of ejection fraction. Recently
      we scanned with a Signa HD 1.5 T (GE, Milwaukee, USA) 8 patients affected by non
      compaction. Transmural Gd-enhancement was detected in 5/8 patients (62%). In all
      patients with late enhancement a reduction of EF has demonstrated. In our opinion
      the late enhancement can depend on a CFR, and is the determinant of the tissue
      Doppler alterations. So the TD alteration is associated with EF, and is an
      indirect index of poor clinical outcome, like EF.

PMID- 18068242
TI  - Acute myocardial infarction preceded by potential triggering activities:
      angiographic and clinical characteristics.
AB  - BACKGROUND: In an investigation of the relationship between myocardial infarction
      (MI) preceded by certain activities or events and coronary angiographic data,
      including the extent of atherothrombotic involvement during acute MI, we
      hypothesized that when comparing patients with MI that was preceded by potential
      triggering activities (PTA "+") to MI without PTA, the former might have a
      distinct pathogenic basis exhibiting different angiographic and clinical
      features. METHODS: In the framework of a national survey on acute coronary
      syndromes conducted during a 2-month period in 2002, 662 acute MI patients with
      complete angiographic data were divided into two groups, according to whether or
      not they reported the presence of specific unusual events or activities
      immediately preceding the onset of MI. RESULTS: One hundred and one patients with
      PTA "+" MI were younger, and included a higher proportion of smokers than their
      counterparts (n=561), who were characterized by a higher frequency of
      hypertension and diabetes. After adjustment for age, gender, prior MI or CABG,
      diabetes, hypertension, current smoking, serum creatinine level, left ventricular
      ejection fraction less than 30%, re-ischemia and Killip class II+, 30-day, 6
      month and 1-year mortality was similar between the two groups. The incidence of
      LAD disease (P<0.01), 3-vessel coronary disease (P<0.03) and TIMI flow 0 or 1
      after coronary angioplasty was significantly lower (P<0.02) in patients with PTA
      "+" MI, while infarct-related right coronary artery (RCA) obstruction was
      significantly higher (OR: 1.7; 95% CI: 1.0-2.9). CONCLUSION: Further
      investigation is needed in order to confirm the association between angiographic
      data and potential triggering activities observed in our study, and to determine
      the mechanisms responsible for this finding.

PMID- 18068243
TI  - Takotsubo cardiomyopathy--a new variant and widening disease spectrum. "Inverted
      Takotsubo" pattern related to catecholamine-toxicity.

PMID- 18068244
TI  - Relationship of plasma brain-type natriuretic peptide levels to left ventricular
      longitudinal function in patients with congestive heart failure assessed by
      strain Doppler imaging.
AB  - BACKGROUND: Plasma brain-type natriuretic peptide (BNP) levels have been used to
      diagnose congestive heart failure (CHF), but significant heterogeneity in BNP
      levels is not explained by standard echocardiographic indexes of cardiac
      function. Recent data indicate that longitudinal left ventricular (LV)
      dysfunction exists in the presence of normal standard echocardiographic indexes
      and BNP was predicted well by LV longitudinal systolic velocity. We examined
      whether longitudinal LV function assessed by strain or strain rate (SR) tissue
      Doppler imaging could be determinants of plasma BNP levels in patients with CHF.
      METHODS: We examined 137 consecutive patients with suspected CHF. Standard
      echocardiography and Doppler flow records were obtained. Strain, and SR at the
      basal and mid parts of the ventricle were investigated in 2 apical views. Tissue
      velocities of mitral annulus were also obtained. Plasma BNP levels were measured
      on the day of echocardiography. RESULTS: Multivariate analysis showed the mean
      longitudinal LV strain (r=0.75, P<0.0001) to be an independent powerful predictor
      of plasma log BNP levels. Subgroup analysis (ejection fraction <50%, n=30;
      ejection fraction >50%, n=107) also showed that the mean longitudinal LV strain
      (r=0.89, P<0.0001; r=0.68, P<0.0001, respectively) was only an independent
      predictor of log BNP levels. CONCLUSION: Longitudinal LV strain is closely
      related to log BNP levels in patients with CHF, both in patients with systolic
      and diastolic heart failure.

PMID- 18068245
TI  - A rare association recognized before cardiac surgery: persistent left superior
      vena cava and secundum atrial septal defect.
AB  - One of the most common congenital anomalies of systemic veins is persistent left
      superior vena cava. Association of persistent left superior vena cava with other
      congenital cardiac diseases is common and frequently encountered during
      diagnostic studies. Contrast echocardiography has an important role in the
      diagnosis. Owing to the fact that cardiopulmonary by-pass procedure may be
      problematic in patients with persistent left superior vena cava, this anomaly
      should be detected before cardiac surgery and required measures should be taken.
      Our case is an association of persistent left superior vena cava detected in a
      patient to be operated for secundum atrial septal defect. We report the case
      owing to its low frequency and to emphasize the importance of detection before
      cardiac surgery.

PMID- 18068246
TI  - Distortion of the terminal portion of the QRS is predictor of shock after primary
      percutaneous coronary intervention for acute myocardial infarction.
AB  - BACKGROUND: Although invasive management of ST segment elevation myocardial
      infarction has improved the clinical outcome, cardiogenic shock (CS) remains an
      important issue. Our purpose was to asses the utility of the initial
      electrocardiogram in detecting patients who are at increased risk of CS after
      percutaneous coronary intervention for acute myocardial infarction. METHODS: We
      evaluated 508 consecutive patients admitted in our Coronary Unit and treated by
      primary angioplasty within 12 h of an ST segment elevation myocardial infarction.
      Patients with cardiogenic shock at admission were excluded. Two groups were
      defined according to the presence of distortion of the terminal portion of the
      QRS in two or more adjacent leads (group 1) or the absence of this pattern (group
      2). RESULTS: There were 99 patients (20%) in group 1 and 409 (80%) in group 2. CS
      developed in 38 patients, 18 in group 1 (18%) and 20 in group 2 (5%), p<0.001.
      Seventeen patients died in hospital, 6 in group 1 (6%) and 11 in group 2 (3%), p
      0.094. Multivariate analysis including clinical, electrocardiographic and
      angiographic variables showed distortion of the QRS as an independent predictor
      of cardiogenic shock (odds ratio 3.17, 95% confidence interval 1.44 to 6.96, p
      0.004), together with Killip class at admission and TIMI 3 flow after
      revascularization. CONCLUSIONS: Distortion of the terminal portion of the QRS
      complex is a strong predictor of cardiogenic shock in STEMI patients. Close
      hemodynamic monitoring should be warranted in patients showing this
      electrocardiographic pattern.

PMID- 18068247
TI  - A novel indicator plant to test the hypersensitivity of phytopathogenic bacteria.
AB  - Hypersensitive response is an important, definitive test to separate plant
      pathogenic bacteria from saprophytes. The current standard protocol uses tobacco
      and four o'clock plants as indicators for Gram negative and Gram positive
      phytopathogenic bacteria, respectively, and inoculation is accomplished by
      infiltrating bacterial suspensions into intact leaves. Both plants, especially
      the four o'clock, have thin leaves which make inoculation difficult, sometimes
      leading to inaccurate tests. Here we propose the use of Sedum hybridum as an
      alternative indicator plant. Sedum plants are readily available, easy to
      propagate and fast growing. Their leaves are much thicker, thus infiltration of a
      bacterial suspension is easier compared to tobacco and four o'clock.
      Additionally, sedum plants can be used universally to test both Gram negative and
      Gram positive phytopathogenic bacteria.

PMID- 18068248
TI  - Gene expression profiling of major depression and suicide in the prefrontal
      cortex of postmortem brains.
AB  - Genome-wide gene expression analysis using DNA microarray has a great advantage
      to identify the genes or specific molecular cascades involved in mental diseases,
      including major depression and suicide. In the present study, we conducted DNA
      microarray analysis of major depression using postmortem prefrontal cortices. The
      gene expression patterns were compared between the controls and subjects with
      major depression. As a result, 99 genes were listed as the differentially
      expressed genes in major depression, of which several genes such as FGFR1, NCAM1,
      and CAMK2A were of interest. Gene ontology analysis suggested an
      overrepresentation of genes implicated in the downregulation or inhibition of
      cell proliferation. The present results may support the hypothesis that major
      depression is associated with impaired cellular proliferation and plasticity.
      Comparison between the controls and suicide victims with major depression,
      bipolar disorder, or schizophrenia was also conducted in the present study. Two
      genes, CAD and ATP1A3, were differentially expressed in the three comparisons in
      the same direction. Interestingly, these two genes were also included in the
      differentially expressed 99 genes in major depression. It may be worth
      investigating the genes in relation to suicide or major depression.

PMID- 18068249
TI  - Nociceptive contribution to the evoked potentials after painful intramuscular
      electrical stimulation.
AB  - Our study aimed at investigating the nociceptive contribution to the
      somatosensory evoked potentials after electrical intramuscular stimulation
      (mSEPs) at painful intensity. Scalp mSEPs were recorded in 10 healthy subjects
      after electrical stimulation of the left brachioradialis muscle at three
      intensities: non-painful (I2), slightly painful (I4) and moderately painful (I6).
      For each intensity, mSEPs were recorded in a neutral condition (NC) in which
      subjects did not have any task, and in an attention condition (AC) in which
      subjects were asked to count the number of stimuli. In both NC and AC, the N120
      and P220 amplitudes were significantly higher at I6 than at I2. While the N120
      amplitude did not vary between NC and AC, the P220 amplitude was significantly
      higher in AC than in NC at all stimulus intensities. Our results suggest that
      nociceptive inputs contribute to the N120 amplitude increase at painful stimulus
      intensity, while the P220 amplitude is more sensitive to changes of subjects'
      attention level. Therefore, the N120 amplitude increase to moderately painful
      stimuli, as compared to non-painful stimuli, may represent a marker of the
      activation of the muscular thin myelinated afferents.

PMID- 18068250
TI  - The sensitivity and specificity of fecal and cecal culture for the detection of
      Campylobacter in Dutch broiler flocks quantified by Bayesian analysis.
AB  - Dutch broiler flocks are routinely tested for the presence of thermotolerant
      Campylobacter spp. using a standard cultural procedure for fecal and cecal
      samples. The objective of this study was to estimate the sensitivity and
      specificity of fecal and cecal culture for detection of Campylobacter
      colonization in broiler flocks in absence of a gold standard. Data from 1600
      flocks were used from two different populations, whereby only flocks with both
      fecal and cecal culture results were included in the analysis. Latent class
      analysis using Bayesian inference was applied to generate the test
      characteristics of fecal and cecal culture. Two statistical models assuming
      conditional dependence of both tests on Campylobacter status were used to compare
      the results. On flock level, the sensitivity of the fecal culture was found to be
      21% (95% CI: 12, 31) and 23% (95% CI: 13, 60), and the specificity was 98% (95%
      CI: 94, 99) and 97% (95% CI: 92, 99) for the two models, respectively. The
      sensitivity of the cecal culture was 64% (95% CI: 37, 89) and 66% (95% CI: 39,
      90), and the specificity was 98% (95 CI: 94, 99) and 95% (95% CI: 72, 99) in
      respective models. The implications of a low sensitivity as in the case of the
      fecal culture is important for the design and interpretation of monitoring
      programmes and may result in excessive false negative test results. Although
      cecal culture is the more sensitive test, substantial misclassification of
      infected flocks may still occur.

PMID- 18068251
TI  - Increased resistance of Escherichia coli O157:H7 to electron beam following
      repetitive irradiation at sub-lethal doses.
AB  - One way that food processors in the United States have been controlling food
      borne pathogens in a non-thermal manner is the application of electron beam (e
      beam) radiation. The development of an increased resistance of Escherichia coli
      O157:H7 to various stressors such to pH, temperature, ionic strength, and
      antibiotics has been demonstrated. The objective of this study was to determine
      if the D(10)-value for E. coli O157:H7 (E. coli) in ground beef increases due to
      repetitive exposure to e-beam at sub-lethal levels. Ground beef samples were
      inoculated with E. coli and incubated to approximately 10(9) CFU/g followed by e
      beam processing. Survivors were enumerated using a standard spread-plating
      technique. Colonies of E. coli survivors from the highest e-beam dose were
      isolated and grown for the next cycle of inoculation in ground beef and e-beam
      processing. Five such consecutive cycles of isolation and e-beam processing were
      performed. The D(10)-values for E. coli survivors following each cycle of e-beam
      processing were calculated from survivor curves. The D(10)-values increased
      (P<0.05) with subsequent cycles of e-beam processing, starting at 0.24+/-0.03 kGy
      for E. coli ATCC strain 35150 and reaching 0.63+/-0.02 kGy for E. coli isolate
      L3. Following four cycles of e-beam processing, the isolate L3 increased (P<0.05)
      its radio-resistance and survived an e-beam dose of 3.0 kGy. Therefore, our data
      demonstrates that e-beam can efficiently inactivate E. coli in food products;
      however, similar to other inactivation techniques, E. coli has a capability to
      develop increased resistance to e-beam if the same populations of E. coli in food
      products are repetitively subjected to e-beam processing. Although the exact
      mechanism for the development of increased radio-resistance of E. coli to e-beam
      is unclear at the moment, based on the available literature regarding increased
      resistance of E. coli to various stressors, it is likely that some genetic
      mechanism in involved. Therefore, we are currently investigating this hypothesis
      with micro-arrays.

PMID- 18068252
TI  - Presence of Clostridium botulinum spores in Matricaria chamomilla (chamomile) and
      its relationship with infant botulism.
AB  - Nowadays, infant botulism is the most important form of human botulism in some
      countries. This illness affects infants younger than 52 weeks of age. The
      infection occurs in the intestinal tract; therefore, ingestion of Clostridium
      botulinum spores with food is proposed. In some countries, people use chamomile
      tea as a household remedy for intestinal colics and given this tea to infants.
      Chamomile can be contaminated with C. botulinum and could be a vehicle of its
      spores. Our aim was to study the prevalence and spore-load of C. botulinum in
      chamomile. We analysed 200 samples; the 7.5% of them were contaminated with
      botulinum spores. However, prevalence of these spores was significantly higher in
      chamomile sold by weight in herbal stores (unwrapped chamomile) than prevalence
      in chamomile sold in tea bags (p=0.0055). The spore-load detected in all positive
      samples was 0.3-0.4 spores per gram of chamomile. We identified C. botulinum
      types A, B, and F in the 53.3%, 6.7%, and 13.3%, respectively. Chamomile
      (principally, unwrapped chamomile) is a potencial vehicle of C. botulinum spores,
      and ingestion of chamomile tea could represent a risk for infant botulism.

PMID- 18068253
TI  - Inhibition of Listeria monocytogenes in dairy products using the bacteriocin-like
      peptide cerein 8A.
AB  - The efficacy of the antimicrobial peptide cerein 8A to control the development of
      Listeria monocytogenes in milk and soft cheese was investigated. The addition of
      160 AU ml(-1) cerein 8A to UHT milk resulted in a decrease of 3 log cycles in
      viable cells within the 14-day period at 4 degrees C. The viable counts of L.
      monocytogenes in pasteurized milk samples containing cerein 8A was lower than
      those observed in controls without bacteriocin. Addition of cerein 8A to Minas
      type soft cheese caused a delay in the start of exponential growth phase,
      although similar counts were observed after day 6. When cerein 8A was used to
      control cheese surface contamination by L. monocytogenes, a decrease of 2 log
      cycles in viable counts of cerein-treated samples was observed during 30 days at
      4 degrees C. This antimicrobial peptide shows potential use as a biopreservative
      for application in dairy products.

PMID- 18068254
TI  - Effect of diet on the concentration of complex Shiga toxin-producing Escherichia
      coli and EHEC virulence genes in bovine faeces, hide and carcass.
AB  - An experiment was conducted to determine whether diets based on structural
      carbohydrate and/or simple sugars, as found in roughage and/or molasses-based
      diets, reduce the bovine faecal populations of Shiga toxin-producing Escherichia
      coli (STEC) isolates containing the eaeA and ehxA genes, referred to as complex
      STEC (cSTEC), compared with typical high starch, grain-based feedlot diets. In
      addition, whether commercial lairage management practices promote or diminish any
      diet-induced responses on the contamination of carcasses was also investigated.
      After 13 days on the dietary treatments total faecal E. coli numbers were
      approximately one log lower in the roughage (R) and roughage +50% molasses (RM)
      diets compared with grain (G) fed animals, this difference varying between 0.5
      and 1 log at lairage. Fermentation patterns were similar in the R and RM diets
      whereas decreased pH and enhanced butyrate fermentation pathways were associated
      with the G diet. A significant decrease in the faecal concentration of the eaeA
      gene occurred when animals were changed from high grain to R and RM diets for 6
      13 days, compared with animals maintained on the G diet. Significantly lower
      concentrations of the ehxA gene were also associated with the R diet.
      Concentrations of the stx(2) gene however, were unaffected by diet. cSTEC were
      infrequently isolated, with the faecal concentrations of these organisms being
      low (<3 log(10) MPN per g faeces). cSTEC were only isolated from animals fed G or
      RM diets, but were never isolated from cattle fed the roughage-based diet, with
      this diet-induced effect sustained following lairage. These organisms were not
      detected on the hide and carcass of animals found to shed cSTEC in their faeces
      and thus appeared uncontaminated with cSTEC.

PMID- 18068255
TI  - Identification of tet(M) in two Lactococcus lactis strains isolated from a
      Spanish traditional starter-free cheese made of raw milk and conjugative transfer
      of tetracycline resistance to lactococci and enterococci.
AB  - Specific PCR and sequencing showed that a tet(M) gene was present in two
      tetracycline-resistant Lactococcus lactis strains isolated from a raw milk,
      starter-free cheese. Hybridisation experiments using as a probe an internal
      segment of the gene obtained by PCR associated tet(M) with plasmids of around the
      same size (30 kbp) in both strains. Molecular analysis of the tetracycline
      resistance loci, including the upstream and downstream regions of the genes,
      showed them to be identical to one other and to the tet(M) encoded by the
      conjugative transposon Tn916. Amplification of Tn916-derived segments suggested
      the transposon was complete in the two L. lactis strains. Further, curing of the
      tetracycline resistance was accompanied by a reduction in size of the plasmids
      comparable to that expected for Tn916. Tetracycline resistance could be
      transferred by conjugation to plasmid-free Lactococcus and Enterococcus strains.
      However, no plasmid DNA was detected among the transconjugants while both tet(M)
      and transposon-related sequences were amplified by PCR. This suggested that only
      the transposon was mobilized.

PMID- 18068256
TI  - Isolation of halotolerant Lactococcus lactis subsp. lactis from intestinal tract
      of coastal fish.
AB  - We isolated lactic acid bacteria from the intestinal tract of the pufferfish
      Takifugu niphobles caught in Shimoda, Shizuoka, Japan by using MRS broth prepared
      with 50% seawater. Additional screening was carried out using phenotypic tests
      such as Gram staining, cell morphology, catalase, oxidase and fermentation of
      glucose. Subsequently 227 isolates screened by the phenotypic tests were
      subjected to species-specific PCR for Lactococcus lactis, resulting in four
      positive isolates. The 16S rRNA gene sequences from three isolates were highly
      similar to that of L. lactis subsp. lactis (DNA database accession number
      M58837), while that of one isolate was identical to that of Leuconostoc
      mesenteroides (AB023246). These isolates were characterized by API 50 CH for
      carbohydrate fermentation and other phenotypic criteria for salt tolerance, and
      the characteristics were compared with those of L. lactis subsp. lactis from a
      cheese starter culture. The carbohydrate fermentation profiles of these isolates
      were characteristic of L. lactis subsp. lactis strains, whereas the tolerance of
      these isolates to salt was higher than that of L. lactis subsp. lactis from the
      cheese starter culture: the new L. lactis isolates showed high salt tolerance in
      MRS-agar plates containing 200% seawater or 6% sodium chloride. This is the first
      report of the isolation of halotolerant strains of L. lactis subsp. lactis from a
      marine environment.

PMID- 18068257
TI  - Genomic sequence of mandarin fish rhabdovirus with an unusual small non
      transcriptional ORF.
AB  - The complete genome of mandarin fish Siniperca chuatsi rhabdovirus (SCRV) was
      cloned and sequenced. It comprises 11,545 nucleotides and contains five genes
      encoding the nucleoprotein N, the phosphoprotein P, the matrix protein M, the
      glycoprotein G, and the RNA-dependent RNA polymerase protein L. At the 3' and 5'
      termini of SCRV genome, leader and trailer sequences show inverse
      complementarity. The N, P, M and G proteins share the highest sequence identities
      (ranging from 14.8 to 41.5%) with the respective proteins of rhabdovirus 903/87,
      the L protein has the highest identity with those of vesiculoviruses, especially
      with Chandipura virus (44.7%). Phylogenetic analysis of L proteins showed that
      SCRV clustered with spring vireamia of carp virus (SVCV) and was most closely
      related to viruses in the genus Vesiculovirus. In addition, an overlapping open
      reading frame (ORF) predicted to encode a protein similar to vesicular stomatitis
      virus C protein is present within the P gene of SCRV. Furthermore, an
      unoverlapping small ORF downstream of M ORF within M gene is predicted
      (tentatively called orf4). Therefore, the genomic organization of SCRV can be
      proposed as 3' leader-N-P/C-M-(orf4)-G-L-trailer 5'. Orf4 transcription or
      translation products could not be detected by northern or Western blot,
      respectively, though one similar mRNA band to M mRNA was found. This is the first
      report on one small unoverlapping ORF in M gene of a fish rhabdovirus.

PMID- 18068259
TI  - How to improve the storage stability of aqueous polymeric film coatings.
AB  - The major aim of this study was to identify an easy tool to improve the long term
      stability of polymeric film coatings applied from aqueous dispersions. Drug
      release profiles from ethylcellulose-coated theophylline pellets were monitored
      during 6 months open storage under ambient and stress conditions ["room
      temperature/ambient relative humidity (RH)" and "40 degrees C/75%RH"]. The
      pellets were cured for 1 or 2 d at 60 degrees C or for 1 or 2 d at 60 degrees
      C/75%RH (followed by 1 d at 60 degrees C for drying). Drug release was measured
      in 0.1 M HCl and in phosphate buffer pH 7.4. Interestingly, the addition of only
      small amounts of poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer
      provided stable drug release profiles under all the investigated conditions,
      irrespective of the type of release medium, coating level, polymer blend ratio
      and curing conditions. The addition of small amounts of propylene glycol alginate
      resulted in unaltered drug release kinetics during open storage under ambient
      conditions, but decreasing theophylline release rates during open storage under
      stress conditions, due to further gradual polymer particle coalescence. When
      adding small amounts of carrageenan to the ethylcellulose coatings, essentially
      stable theophylline release patterns (with slight variations) were obtained. As
      coating conditions were not optimized for each system, further work is necessary
      to distinguish polymer from process effects. The observed stabilizing effects of
      the investigated added polymers might be attributable to their hydrophilic
      nature, trapping water within the coatings during film formation and, thus,
      facilitating polymer particle coalescence. This new concept can be used to
      overcome one of the major practical obstacles associated with aqueous polymeric
      film coatings today: storage instability.

PMID- 18068258
TI  - A fast and sensitive method for measuring the integrity of siRNA-carrier
      complexes in full human serum.
AB  - SiRNA based therapeutics are currently under investigation for treatment of
      cancer and viral infections. Upon intravenous administration, the nanoscopic
      delivery systems which carry the siRNA need to be stable in serum, an aspect
      which is often overlooked in numerous publications on siRNA delivery systems.
      Techniques currently available for studying the dissociation of siRNA-liposome
      complexes are time consuming and incompatible with full serum. We therefore
      developed a fluorescence fluctuation spectroscopy (FFS) based method which allows
      to monitor the integrity of siRNA-carrier complexes. The method can very rapidly
      provide quantitative information on the complex integrity in biological media,
      like full human serum, and at very low siRNA concentrations (approximately 20 nM
      siRNA). Information on the integrity of intravenously injected siRNA
      nanoparticles in serum is crucial. Consequently, the FFS method reported in this
      work may find broad applicability in the field of siRNA-carrier design.

PMID- 18068260
TI  - Formulation of lipid-based delivery systems for oral administration: materials,
      methods and strategies.
AB  - Oral lipid-based drug delivery systems may include a broad range of oils,
      surfactants, and cosolvents. This diversity makes comparison of lipid-based
      formulations difficult. Although the relationship between formulation and drug
      absorption is understood at a conceptual level, performance in vivo cannot be
      predicted with confidence at present. The Lipid Formulation Classification System
      (LFCS) identifies the factors which are likely to affect performance in vivo.
      There is now a need to establish performance criteria which will facilitate in
      vitro-in vivo correlation studies. In this review we discuss the properties of
      excipients, and identify criteria for selection of excipients for lipid-based
      formulations. Excipients are discussed in the context of the LFCS, our existing
      knowledge of the fate of these materials during dispersion and digestion, and the
      likely consequences of their use in formulations. We outline the formulation
      strategies that can be used for each type of lipid formulation, and suggest a
      framework for the in vitro testing of each type. Finally we address the choice of
      lipid formulations in relation to the physicochemical properties of the drug.

PMID- 18068261
TI  - Particle design of poorly water-soluble drug substances using supercritical fluid
      technologies.
AB  - In order to improve the dissolution properties of poorly water-soluble drugs,
      some drugs were subjected to micronization or prepared as composite particles
      using supercritical fluid (SCF) technology with carbon dioxide (CO(2)).
      Solubility in CO(2) is the key when using this method. Solubility affects the
      supersaturation of the materials in the solvent as well as the mass transfer of
      that solvent, which are both critical to the micronization of the materials and
      the formation of the composite particles. Some useful techniques that can be used
      to avoid the problems posed by the characteristics of the drug itself are
      combining SC-CO(2) with other technologies, such as the formation of coacervates
      or emulsions, and other equipment types, such as milling or ultrasound fields.
      Another advantage of SCF technology is that it is considered to be green
      chemistry. SC-CO(2) can improve the solubility of poorly water-soluble drug
      substances using few or no organic solvents and with little or no heating.

PMID- 18068262
TI  - Colloid transport in unsaturated porous media: the role of water content and
      ionic strength on particle straining.
AB  - Packed column and mathematical modeling studies were conducted to explore the
      influence of water saturation, pore-water ionic strength, and grain size on the
      transport of latex microspheres (1.1 microm) in porous media. Experiments were
      carried out under chemically unfavorable conditions for colloid attachment to
      both solid-water interfaces (SWI) and air-water interfaces (AWI) using negatively
      charged and hydrophilic colloids and modifying the solution chemistry with a
      bicarbonate buffer to pH 10. Interaction energy calculations and complementary
      batch experiments were conducted and demonstrated that partitioning of colloids
      to the SWI and AWI was insignificant across the range of the ionic strengths
      considered. The breakthrough curve and final deposition profile were measured in
      each experiment indicating colloid retention was highly dependent on the
      suspension ionic strength, water content, and sand grain size. In contrast to
      conventional filtration theory, most colloids were found deposited close to the
      column inlet, and hyper-exponential deposition profiles were observed. A
      mathematical model, accounting for time- and depth-dependent straining, produced
      a reasonably good fit for both the breakthrough curves and final deposition
      profiles. Experimental and modeling results suggest that straining--the retention
      of colloids in low velocity regions of porous media such as grain junctions--was
      the primary mechanism of colloid retention under both saturated and unsaturated
      conditions. The extent of stagnant regions of flow within the pore structure is
      enhanced with decreasing water content, leading to a greater amount of retention.
      Ionic strength also contributes to straining, because the number of colloids that
      are held in the secondary energy minimum increases with ionic strength. These
      weakly associated colloids are prone to be translated to stagnation regions
      formed at grain-grain junctions, the solid-water-air triple point, and dead-end
      pores and then becoming trapped.

PMID- 18068263
TI  - Laser treatment of pediatric vascular lesions: Port wine stains and hemangiomas.
AB  - Pediatric vascular lesions can be medically threatening and psychologically
      distressing to patients. This article reviews literature on the laser treatment
      of two common pediatric vascular lesions, port wine stains and hemangiomas. The
      purpose of this report was to distinguish the lesions from one another and to
      present the advantages, disadvantages, complications, and limitations of laser
      treatment for each lesion type. This review is not a comprehensive inventory but
      instead highlights the studies that best show promising results or the
      limitations of laser treatment for the lesions. Overall, port wine stain laser
      treatment promoted notable clearing with low side effects, whereas hemangioma
      laser treatment provided inconsistent benefits and severe side effects
      occasionally. Laser treatment of port wine stains is safe and effective, but
      laser treatment of hemangiomas remains controversial and is best for lesions
      without deeper components.

PMID- 18068264
TI  - Screening program reduced melanoma mortality at the Lawrence Livermore National
      Laboratory, 1984 to 1996.
AB  - BACKGROUND: Worldwide incidence of cutaneous malignant melanoma has increased
      substantially, and no screening program has yet shown reduction in mortality. We
      evaluated results of an educational campaign designed to promote self-examination
      and targeted screening at the Lawrence Livermore National Laboratory (LLNL).
      METHODS: Thickness and crude incidence of melanomas detected during 3 phases of
      increasing melanoma surveillance were studied. These periods were: (1)
      preawareness (1969-1975), (2) early awareness of increased melanoma risk (1976
      1984); and (3) screening program (1984-1996). Melanoma mortality was derived from
      data recorded in the National Death Index search. The expected annual number of
      deaths from melanoma among LLNL employees was calculated by using California
      mortality data matched by age, sex, and race/ethnicity and adjusted to exclude
      deaths from melanoma diagnosed before the program began or before employment at
      LLNL. RESULTS: Crude incidence of melanomas thicker than 0.75 mm decreased during
      the 3 periods from 22.1 to 15.13 to 4.62 cases per 100,000 person-years (P = .001
      by chi-square for trend) with the larger decrease from the active screening
      program. The crude incidence of melanoma measuring less than 0.75 mm in thickness
      increased and then decreased slightly without a significant linear trend, and
      crude incidence of in situ melanoma increased substantially. No eligible melanoma
      deaths occurred among LLNL employees during the screening period, whereas the
      expected number of deaths was calculated to be 3.39 deaths (P = .034).
      LIMITATIONS: The study design was not randomized or controlled. The methodology
      for adjusting expected mortality for the exclusion of employees diagnosed with
      melanoma before the screening period was devised for this study. DISCUSSION:
      Increasing community awareness of melanoma was associated with a progressive
      decreasing incidence of thicker melanoma. The education, self-examination, and
      selective program generated the larger reduction in incidence of melanoma thicker
      than 0.75 mm. This campaign decreased the melanoma-related mortality to zero. The
      statistically significant decrease in mortality persisted for at least 3 years
      after employees retired or otherwise left the laboratory.

PMID- 18068265
TI  - Imiquimod 5% cream for treatment of HIV-negative Kaposi's sarcoma skin lesions: A
      phase I to II, open-label trial in 17 patients.
AB  - BACKGROUND: Kaposi's sarcoma (KS), a virus-associated neoplasm, can be treated
      locally or systemically with interferon alfa. Therefore, imiquimod, an immune
      response modifier able to induce interferon-alpha secretion in situ, could prove
      a good local treatment for KS skin lesions. OBJECTIVE: We sought to determine the
      efficacy and safety of imiquimod 5% cream for the topical treatment of classic or
      endemic KS skin lesions in patients who are HIV negative. METHODS: We conducted a
      prospective, open-label, single center, phase II clinical trial. Imiquimod cream
      was applied under occlusion 3 times a week for 24 weeks. The main efficacy end
      points were the safety of topical imiquimod and the overall clinical response in
      patients evaluated on the basis of modified AIDS Clinical Trials Group criteria
      at 36 weeks. The statistical analysis was based on the intent-to-treat data set.
      RESULTS: Seventeen patients were enrolled. Eight (47%) presented objective
      overall clinical response (2 complete and 6 partial responses). Tumor progression
      was noted in 6 patients. The most frequent side effects were local itching and
      erythema, seen in 9 patients (53%). LIMITATIONS: This was not a randomized
      placebo-controlled study and was restricted to a small number of patients.
      CONCLUSION: Topical imiquimod 5% cream had antitumor activity in about half the
      patients with classic and endemic KS and was generally well tolerated.

PMID- 18068266
TI  - "I forgot to shave my hands": A case of spiny keratoderma.
AB  - A 57-year-old Caucasian man presented with multiple asymptomatic spiny papules on
      the palms and soles that he had been shaving off with a razor for many years. He
      was otherwise healthy with no personal or family history of skin disease or
      malignancy. A diagnosis of spiny keratoderma of the palms and soles or "music box
      spine dermatosis" was made. The clinical, histologic, and electron-microscopic
      features of spiny keratoderma are distinct. This entity previously had multiple
      classifications and it is important to distinguish it from other keratodermas as
      some keratodermas can be linked to cutaneous and internal malignancies and
      conditions: polycystic kidney disease, liver cysts, Darier's disease, and
      hyperlipoproteinemia among others. Spiny keratodermas can have systemic
      associations and do not resolve spontaneously. Treatment is generally
      ineffective.

PMID- 18068267
TI  - The Attitudes to Chocolate Questionnaire: psychometric properties and
      relationship to dimensions of eating.
AB  - The aim of the present study was to evaluate the psychometric properties of the
      Attitudes to Chocolate Questionnaire (ACQ). We analyzed the factor structure of
      the ACQ by conducting exploratory and confirmatory factor analyses in a sample of
      healthy adults and a sample of dietician students. Further, the relationship
      between the resulting ACQ factors and dimensions of eating behavior, personality,
      emotionality, and tests of the pleasantness, sweetness, and intensity of sugar
      and chocolate was examined. The results yielded a clear two-factor structure of
      the ACQ: The first factor (guilt) was composed of items concerning negative
      consequences of chocolate eating including the feeling of guilt. The second
      factor (craving) comprised items related to craving and emotional chocolate
      eating. Guilt correlated significantly with "emotional eating", "restrained
      eating", and with neuroticism. Craving correlated significantly with "emotional
      eating" and "external eating", with neuroticism, and with the "difficulty
      identifying feelings" facet of the Toronto Alexithymia Scale; further, it
      correlated highly with the average reported chocolate consumption and with the
      ratings of the intensity of taste of sugar. In conclusion, results support the
      validity of the German version of the ACQ and showed a stable factor structure
      and a good internal consistency.

PMID- 18068268
TI  - Laryngoscope handles in a medical intensive care unit: the level of bacterial and
      occult blood contamination.

PMID- 18068269
TI  - Behavioral controls of food intake.
AB  - Recent conceptualizations of food intake have divided ingestive behavior into
      multiple distinct phases. Here, we present a temporally and operationally defined
      classification of ingestive behaviors. Importantly, various physiological signals
      including hypothalamic peptides are thought to impact these distinct behavioral
      phases of ingestion differently. In this review, we summarize a number of
      behavioral assays designed to delineate the effects of hormone and peptide
      signals that influence food intake on these ingestive mechanisms. Finally, we
      discuss two issues that we have encountered in our laboratory which may obstruct
      the interpretation of results from these types of studies. First, the influence
      of previous experience with foods used in these behavioral tests and second, the
      importance of the nutrient composition of the selected test foods. The important
      conclusion discussed here is that the behavioral analysis of ingestion is
      accompanied by theoretical constructs and artificial divisions of biological
      realities and the appreciation of this fact can only increase the opportunities
      of contemporary behavioral scientists to make significant and novel observations
      of ingestive behaviors.

PMID- 18068271
TI  - Synthesis, pharmacological activity and hydrolytic behavior of ethylenediamine
      and benzathine conjugates of ibuprofen.
AB  - For reducing the gastrointestinal toxicity associated with ibuprofen, its
      carboxylic group was masked by synthesizing its amide conjugates with
      ethylenediamine and benzathine (4a, 4b, respectively) by carbodiimide assisted
      coupling method. In vitro hydrolysis of conjugates showed that they were stable
      in HCl buffer (pH 1.2) indicating that the prodrugs did not break in stomach and
      there was no release of ibuprofen at gastric pH, whereas in phosphate buffer (pH
      7.4) they undergo significant hydrolysis and thus release ibuprofen in adequate
      amounts following first order kinetics. The ibuprofen conjugates 4a, 4b were
      retaining anti-inflammatory activity intact and exhibited better analgesic
      activity along with much reduced ulcerogenicity. These findings suggested that
      both the conjugates are better in action as compared to parent drug and are
      advantageous in having less gastrointestinal side effects. Compound 4b however
      showed better analgesic activity and longer action (t(1/2)) than 4a, and hence it
      could be considered as a better candidate for prodrug among the two.

PMID- 18068270
TI  - Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid.
AB  - Abnormal interaction of beta-amyloid 42 (Abeta42) with copper, zinc and iron
      induce peptide aggregation and oxidation in Alzheimer's disease (AD). However, in
      health, Abeta degradation is mediated by extracellular metalloproteinases,
      neprilysin, insulin degrading enzyme (IDE) and matrix metalloproteinases. We
      investigated the relationship between levels of Abeta and biological metals in
      CSF. We assayed CSF copper, zinc, other metals and Abeta42 in ventricular autopsy
      samples of Japanese American men (N=131) from the population-based Honolulu Asia
      Aging Study. There was a significant inverse correlation of CSF Abeta42 with
      copper, zinc, iron, manganese and chromium. The association was particularly
      strong in the subgroup with high levels of both zinc and copper. Selenium and
      aluminum levels were not associated to CSF Abeta42. In vitro, the degradation of
      synthetic Abeta substrate added to CSF was markedly accelerated by low levels
      (2microM) of exogenous zinc and copper. While excessive interaction with copper
      and zinc may induce neocortical Abeta precipitation in AD, soluble Abeta
      degradation is normally promoted by physiological copper and zinc concentrations.

PMID- 18068272
TI  - Pyrimido[1,2-a]quinoxaline 6-oxide and phenazine 5,10-dioxide derivatives and
      related compounds as growth inhibitors of Trypanosoma cruzi.
AB  - Two different families of N-oxide containing heterocycles were evaluated as in
      vitro growth inhibitors of T. cruzi. Both families of heterocycles were selected
      from our in-house library of compounds as analogues of active anti-T. cruzi N
      oxide containing heterocycles. Derivatives from pyrimido[1,2-a]quinoxaline 6
      oxide family were poorly active at the assayed doses. However, phenazine 5,10
      dioxide derivatives displayed good to excellent anti-T. cruzi activities. The
      anti-T. cruzi activity of phenazine derivatives was related to substituent'
      electronic descriptors, sigma(p)(-). Derivatives 19, 20 and 23 were the most
      cytotoxic compounds against the protozoan and became excellent hit for further
      structural modifications.

PMID- 18068273
TI  - Syntheses and evaluation of 3-(3-bromo phenyl)-5-phenyl-1-(thiazolo [4,5-b]
      quinoxaline-2-yl)-2-pyrazoline derivatives.
AB  - A variety of 3-(3-bromo phenyl)-5-phenyl-1-(thiazolo [4,5-b] quinoxaline-2-yl)-2
      pyrazoline were obtained by the refluxing of 1-N-thiocarbamoyl 3,5-diphenyl-2
      pyrazoline with 2,3-dichloroquinoxaline. The chemical structures of the compounds
      were elucidated by UV, IR, (1)H NMR, and (13)C NMR spectroscopy. The purity of
      the compounds was confirmed by their elemental analysis. The antiamoebic activity
      of these compounds was evaluated by microdilution method against HMI:IMSS strain
      of Entamoeba histolytica and the IC(50) values were compared with the standard
      drug metronidazole. Some of the quinoxaline derivatives showed less IC(50) values
      than metronidazole. To elucidate the toxic effect, MTT assay was performed using
      kidney epithelial cell line. The results showed that all the compounds are non
      toxic.

PMID- 18068274
TI  - Novel bradykinin-1 antagonists containing a (1,2,3,4-tetrahydro-isoquinolin-1
      yl)acetic acid scaffold.
AB  - A novel B(1) antagonist core was utilized and the effects of modification of its
      amide side chain on the biological activity were tested. The imino functional
      group of isoquinolin-1-ylacetic acid and its 6,7-dimethoxy variant was
      sulfonylated (4-toluenesulfonyl), while the acetyl side chain was converted to
      amides. Three of the synthesized compounds exhibited significant activity at the
      recombinant human B(1) receptors in binding tests and also in a functional assay.

PMID- 18068275
TI  - Radial Distribution Function descriptors for predicting affinity for vitamin D
      receptor.
AB  - The QSAR is an alternative method for the research of new and better Vitamin D
      analogues with affinity for the VDR receptor. This paper describes the results of
      applying the Radial Distribution Function (RDF descriptors) approach for
      predicting the VDR affinity of 38 vitamin D analogues. The model described 80% of
      the experimental variance, with a standard deviation of 0.35. Leave-one-out,
      bootstrapping and external set validation were carried out with the aim of
      evaluating the predictive power of the model. The values of their respective
      squared correlations coefficients were 0.72, 0.70 and 0.79. The RDF approach was
      compared with four other predictive models, but none of these could explain more
      than 71.0% of the variance with six variables in their respective models.

PMID- 18068276
TI  - How much cervical cancer in Australia is vaccine preventable? A meta-analysis.
AB  - This study aimed to estimate the proportion of cervical cancer attributable to
      high risk HPV types covered by the prophylactic HPV vaccines (HPV types 16 and
      18) in Australia. By applying a systematic search strategy and established
      inclusion criteria, seven studies containing 553 cervical cancers were identified
      for inclusion. The most frequent types identified were HPV16 (60.4%), HPV18
      (19.7%) and HPV45 (4.6%). Overall 80.1% (95%CI 72.7-87.8%) contained types 16 or
      18. Removing 13 cancers with both types, an HPV16/18 vaccine could have prevented
      77.7% of cervical cancers. This finding implies that Australia may have more to
      gain from the adoption of currently formulated HPV vaccines than other countries.

PMID- 18068277
TI  - Lipopentapeptide induces a strong host humoral response and distinguishes
      Mycobacterium avium subsp. paratuberculosis from M. avium subsp. avium.
AB  - BACKGROUND: Many non-tuberculous mycobacteria synthesize abundant
      glycopeptidolipids (GPLs). These surface-located GPLs are involved in
      pathogenicity by interfering with the host immune system. In Mycobacterium avium
      subsp. avium (Mav), GPLs consist of a lipopeptide core composed of a tetrapeptide
      O-linked to mono- and oligo-saccharides. The biosynthesis pathway of the simplest
      GPLs is now relatively well understood and involves probably more than fifteen
      genes. Whereas it is very obvious that most, if not all, of the Mav isolates
      produce GPLs, the picture is not as clear for M. avium subsp. paratuberculosis
      (Map), the etiologic agent of Johne's disease in cattle, and several conflicting
      data have been produced. METHODS: Biochemical analysis of a large set of
      characterized Map isolates showed that all Map strains tested produce a
      lipopentapeptide (L5P) instead of GPLs. To provide a genomic basis for the
      synthesis of this compound, the recently published genome sequence of Map was
      explored using in silico methods. Even though Map produces a lipopeptide rather
      than GPL, its genome contains nevertheless a locus highly similar to the GPL
      biosynthetic pathway of Mav. We showed that the module composition of the non
      ribosomal protein synthase (Nrp) of Map, the enzyme involved in the synthesis of
      the peptidyl moiety, is dramatically different from that of other GPL producers
      such as M. smegmatis (Ms) and Mav and is in agreement with the amino acid content
      of the L5P. We also showed that the peptidyl moiety of the L5P is a target for a
      strong specific humoral response in Map infected animals. CONCLUSIONS: These
      genomic and biochemical differences may help to unambiguously distinguish Map
      from Mav and also from M. bovis, to reclassify related strains of the Map species
      and to allow the convenient and specific diagnosis of paratuberculosis.

PMID- 18068278
TI  - Assessment, validation and intercomparison of operational models for predicting
      tritium migration from routine discharges of nuclear power plants: the case of
      Loire River.
AB  - During last decades, a number of projects have been launched to validate models
      for predicting the behaviour of radioactive substances in the environment. The
      project of the "Aquatic" working group of the project EMRAS (Environmental
      Modelling for Radiation Safety) organised by the International Atomic Energy
      Agency (IAEA) was based on the validation and assessment of models for predicting
      the behaviour of radionuclides in the aquatic ecosystems. The present paper
      describes a blind test of models aimed at assessing the dispersion of tritium
      releases in the Loire River (France), on a large domain ( approximately 350km)
      and on a period of six months, by comparing the results obtained by operational
      to-experimental values of tritium concentration at Angers, a city along the Loire
      River. The common conclusion is that the models used by the different
      participants namely 1D models and models based on a schematic hydraulic (box
      models) are reliable tools for tritium transport modelling. Nevertheless, the
      importance of proper and detailed hydrological data for the appropriate
      prediction of pollutant migration in water is demonstrated by the example
      provided during this study.

PMID- 18068279
TI  - Educational priorities and current involvement in genetic practice: a survey of
      midwives in the Netherlands, UK and Sweden.
AB  - OBJECTIVE: to investigate whether practising midwives are adequately prepared to
      integrate genetic information into their practice. DESIGN: a cross-sectional,
      postal, structured questionnaire survey was sent to practising midwives. SETTING:
      practising midwives from the Netherlands (NL), Sweden (SE) and the United Kingdom
      (UK). PARTICIPANTS: 1021 replies were received, achieving a response rate of 62%.
      FINDINGS: 79% (799/1015) of midwives reported attending courses with some
      'genetic content' during their initial training. Sixty-eight per cent (533/784)
      judged this to have been useful for clinical practice. Variation was seen between
      countries in the amount of genetic content in post-registration training (SE 87%,
      NL 44%, UK 17%) and most was considered useful. Questions assessing clinical
      activity identified a current need for genetic knowledge. Midwives described low
      levels of self-reported confidence both in overtly genetic procedures and in
      everyday tasks that were underpinned by genetic knowledge. For eight of the 12
      procedures, fewer than 20% of midwives considered themselves to be confident.
      Differences were apparent between countries. Midwives identified psychosocial,
      screening and risk assessment aspects of genetic education as being important to
      them, rather than technical aspects or genetic science. CONCLUSIONS: given the
      low reported confidence with genetic issues in clinical practice, it is essential
      that this is addressed in terms of the amount, content and targeting of genetic
      education. This is especially important to ensure the success of national
      antenatal and baby screening programmes. The results of this study suggest that
      midwives would welcome further training in genetics, addressing genetic topics
      most relevant to their clinical practice.

PMID- 18068280
TI  - Identifying research priorities for midwifery in Ireland.
AB  - OBJECTIVE: to identify research priorities for midwifery in Ireland in the short,
      medium and long term. METHOD: a three-round Delphi survey design was used to
      identify midwifery research topics. Issues identified through content analysis
      formed Questionnaires 2 and 3. Participants rated the importance of each topic
      (1=low importance to 7=high importance), and a mean score of 6.0 or more was
      considered a priority issue. A final discussion group set short-, medium- or long
      term timeframes for the research topics. PARTICIPANTS: 334 midwives were
      recruited from a national invitation to all midwives. Response rates were 43%
      (Round 1; 142/334), 85% (Round 2; 121/142) and 81% (Round 3; 98/121). Nine
      consumers of maternity services were included in the discussion group workshop.
      FINDINGS: participants identified 11 clinical, eight management, and seven
      education midwifery research topics with six high-priority issues: promoting
      woman-centred care (management), promoting the distinctiveness of midwifery
      (education), satisfaction with care (clinical), care in labour (clinical),
      preparation for practice (clinical), and promoting research/evidence-based
      practice (education). KEY CONCLUSIONS: this research sought to achieve consensus
      amongst a representative sample of midwives on the priorities for midwifery
      research in Ireland. Midwives can now select topics for graduate or other
      research studies of importance to practice, management and education. Funding
      agencies can confidently direct the allocation of national and local funding for
      priority areas of midwifery research within Ireland.

PMID- 18068281
TI  - Supportive care, growth factors, and new therapies in myelodysplastic syndromes.
AB  - Treatment of myelodysplastic syndromes (MDS) has evolved to encompass a broad
      spectrum of therapies aiming to inhibit apoptosis, promote hemopoiesis, and
      reduce proliferation of clonal immature cells. A small but expanding cohort of
      patients with MDS may be cured, but for the majority the aim of treatment is to
      prolong survival and to improve quality of life. Patients with low-risk MDS
      mainly suffer from the effects of severe anemia and an important therapeutic goal
      is to maintain acceptable hemoglobin levels by optimal transfusion regimens or by
      erythropoietin+/-granulocyte-colony-stimulating factor, which normalizes
      hemoglobin levels or abolish transfusion need in around 40% of patients.
      Lenalidomide has emerged as a drug of choice for patients with low-risk MDS and a
      5q deletion, leading to complete erythroid response and cytogenetic remission in
      2/3 of patients. A small cohort of younger patients may show excellent responses
      to anti-thymocyte globulin. Patients with more advanced disease may respond to
      treatment with the hypomethylating agents azacytidine and decitabine, who both
      have been shown to prolong time to leukemic transformation / death in MDS. In
      addition, there are several new agents under clinical investigation targeted to
      potential mechanisms of disease and progression in MDS. New therapeutic drug
      include inhibitors of angiogenesis, histone deacetylation, tyrosine kinases and
      farnesylation, as well as drugs interacting with apoptotic mechanisms. The role
      of these, alone and in combination with more established therapies will be
      discussed.

PMID- 18068282
TI  - Copper desorption in flooded agricultural soils and toxicity to the Florida apple
      snail (Pomacea paludosa): implications in Everglades restoration.
AB  - Copper (Cu) desorption and toxicity to the Florida apple snail were investigated
      from soils obtained from agricultural sites acquired under the Comprehensive
      Everglades Restoration Plan. Copper concentrations in 11 flooded soils ranged
      from 5 to 234 mg/kg on day 0 and from 6.2 to 204 mg/kg on day 28 (steady-state).
      The steady-state Cu concentration in overlying water ranged from 9.1 to 308.2
      microg/L. In a 28-d growth study, high mortality in snails occurred within 9 to
      16 d in two of three soil treatments tested. Growth of apple snails over 28 d was
      affected by Cu in these two treatments. Tissue Cu concentrations by day 14 were
      12-23-fold higher in snails exposed to the three soil treatments compared to
      controls. The endangered Florida snail kite and its main food source, the Florida
      apple snail, may be at risk from Cu exposure in these managed agricultural soil
      water ecosystems.

PMID- 18068283
TI  - Modelling and mapping long-term risks due to reactive nitrogen effects: an
      overview of LRTAP convention activities.
AB  - Long-range transboundary air pollution has caused severe environmental effects in
      Europe. European air pollution abatement policy, in the framework of the UNECE
      Convention on Long-range Transboundary Air Pollution (LRTAP Convention) and the
      European Union Clean Air for Europe (CAFE) programme, has used critical loads and
      their exceedances by atmospheric deposition to design emission abatement targets
      and strategies. The LRTAP Convention International Cooperative Programme on
      Modelling and Mapping Critical Loads and Levels and Air Pollution Effects, Risks
      and Trends (ICP M&M) generates European critical loads datasets to enable this
      work. Developing dynamic nitrogen flux models and using them for a prognosis and
      assessment of nitrogen effects remains a challenge. Further research is needed on
      links between nitrogen deposition effects, climate change, and biodiversity.

PMID- 18068284
TI  - Efficacy of methylphenidate, psychosocial treatments and their combination in
      school-aged children with ADHD: a meta-analysis.
AB  - INTRODUCTION: This meta-analysis compares effect-sizes of methylphenidate and
      psychosocial treatments and their combination on ADHD, concurrent oppositional,
      conduct symptoms, social behaviors and academic functioning. METHOD: Several
      databases (PubMed, PsycInfo, ISI Web of Science) were searched for articles
      published between 1985 and September 2006. Inclusion criteria were: a diagnosis
      of ADHD; age from 6-12 years; a randomized controlled treatment design; efficacy
      established with parent and teacher rating scales; psychosocial treatments used
      were described as behavioral or cognitive-behavioral; the methylphenidate
      treatment was short-acting; and finally, treatment was conducted in a clinical
      setting. RESULTS: ADHD outcomes showed large mean weighted effect-sizes for both
      methylphenidate and combined treatments, psychosocial treatments had a moderate
      mean weighted effect-size; a similar pattern emerged for oppositional and
      conducted behavior symptoms. Social behavior outcomes showed comparable moderate
      mean weighted effect-sizes for all treatments, while on academic functioning, all
      treatments had low mean weighted effect-sizes. There was no correlation between
      duration of psychosocial treatment and effect-size. CONCLUSIONS: Both
      methylphenidate and psychosocial treatments are effective in reducing ADHD
      symptoms. However, psychosocial treatment yields smaller effects than both other
      treatment conditions. Psychosocial treatment has no additional value to
      methylphenidate for the reduction of ADHD and teacher rated ODD symptoms.
      However, for social behavior and parent rated ODD the three treatments were
      equally effective. For improvement of academic functioning no treatment was
      effective.

PMID- 18068285
TI  - A case series of increased libido and spontaneous orgasm associated with
      venlafaxine treatment.

PMID- 18068286
TI  - Extensive craving in high dose zolpidem dependency.

PMID- 18068287
TI  - Ultra short manic-like episodes after antidepressant augmentation with modafinil.

PMID- 18068288
TI  - Distribution of ochratoxin A in plasma and tissues of rats fed a naturally
      contaminated diet amended with micronized wheat fibres: effectiveness of
      mycotoxin sequestering activity.
AB  - The effectiveness of micronized wheat fibres (MWF) alone or in association with
      yeast cell walls (YCW) as active adsorbents to decrease, in vivo, the levels of
      ochratoxin A (OTA) was checked in a total of 48 rats, equitably distributed into
      four groups: (1) control; (2) OTA naturally contaminated diet (2.2 microg/g); (3)
      OTA naturally contaminated diet (2.2 microg/g) amended with MWF (2%); (4) OTA
      naturally contaminated diet (2 microg/g) amended with MWF (1.8%) in association
      with YCW (0.2%). A 4 week experimental period corresponding to a daily intake in
      the range of 132.2-146.1 microg OTA/kg bw decreased the rat body weight gains, as
      compared to the controls. The adsorbents did not significantly alleviate the
      growth depression caused by the contaminated diet. However, a significant
      protective effect of MWF was observed in terms of OTA concentration in plasma
      (40.5% decrease), kidney (28.1% decrease) and liver (38.8% decrease). Mixing this
      sorbent with the YCW did not significantly improve its protective activity
      against OTA. The faecal OTA concentrations were higher for the MWF and MWF+YCW
      treated animals, as compared to the positive control (group II). Taken together,
      these results suggest that MWF are a promising tool to counteract the toxic
      effects of OTA naturally contaminated diets.

PMID- 18068289
TI  - Influence of ferulic acid on nicotine-induced lipid peroxidation, DNA damage and
      inflammation in experimental rats as compared to N-acetylcysteine.
AB  - We examined the effect of ferulic acid (FA), a naturally occurring phenolic
      compound on lipid peroxidation and endogenous antioxidant status, DNA damage and
      inflammation in nicotine-administered Wistar rats. The effect of FA against
      nicotine toxicity was compared with N-acetylcysteine (NAC), a well-known
      antioxidant. Lung toxicity was induced by subcutaneous injection of nicotine at a
      dose of 2.5mg/kg body weight (5 days a week, for 22 weeks) and FA and NAC were
      given simultaneously by intragastric intubation for 22 weeks. Seventy two Wistar
      rats were divided into six groups: (i) control, (ii) nicotine, (iii) nicotine+FA
      (iv), nicotine+NAC, (v) FA and (vi) NAC. At the end of the experimental period,
      cellular damage was assessed by measuring the activities of lactate dehydrogenase
      and alkaline phosphatase in plasma, which were significantly elevated in nicotine
      administered rats when compared with control group. Enhanced lipid peroxidation
      (evaluated by measuring the thiobarbituric acid reactive substances and
      hydroperoxides) was accompanied by a significant decrease in the endogenous
      antioxidant status viz., superoxide dismutase, catalase, glutathione peroxidase
      and reduced glutathione in circulation, lung and liver of nicotine-treated rats
      when compared with control group. DNA single strand breaks (evaluated by comet
      assay) and frequency of micronuclei were significantly increased in peripheral
      blood of nicotine-treated rats when compared with control. Our Western blot
      analysis showed a significant increase in the expression of cyclooxygenase-2 and
      NF-kappaB in lung and liver of nicotine-treated rats. FA and NAC co-treated rats
      showed a significant decrease in the activities of circulatory lactate
      dehydrogenase and alkaline phosphatase, the levels of lipid peroxidative markers
      (in circulation, lung and liver), DNA single stranded breaks (comet parameters),
      micronuclei frequency (in the whole blood) and expression of cyclooxygenase-2 and
      Nf-kappaB (in lung and liver tissues), and significant increase in antioxidant
      status (in circulation, lung and liver). The protection of FA against nicotine
      induced toxicity was merely equal to the effect of NAC. FA and NAC treatment
      alone did not produce any damage to control rats. Thus, we propose that FA exerts
      protective effect against nicotine toxicity by modulating the lipid peroxidation,
      inflammation, DNA damage and endogenous antioxidant status.

PMID- 18068291
TI  - Edge-strength of flowable resin-composites.
AB  - OBJECTIVES: To evaluate in vitro the failure-forces of flowable composites at
      different distances from an interface edge of a bulk material. METHODS: Seven
      materials were investigated. An edge-strength testing instrument (CK10) was used
      in this study. Fourteen disc specimens were prepared (12 mm x 2.5 mm) for each
      material using Teflon moulds, with a layering technique and light curing at 500
      mW/cm2. Measurements were made (n=5 per distance) at 0.4mm until 1.0mm distance
      from the edge with 0.1mm interval. All specimens prepared were stored in
      distilled water at 37 degrees C for 1 week. The failure-force was recorded for
      each test and the failure mode was examined under the integral microscope of the
      CK10. One-way ANOVA followed by Tukey post-hoc test at the significance level of
      0.05 was used for statistical analysis. RESULTS: The highest failure-force at
      0.5mm (edge-strength) was found with Grandio flow (130.2N) while the lowest was
      with Filtek flow (103.6N). Significant correlation was found between the failure
      forces and the increasing distance from the edge in all flowable composites
      giving coefficients ranging from r2=0.98 to 0.95. However, no correlation was
      found between the failure-forces and the percent filler (wt.%) of flowable
      composites at all distances. Two modes of failure were observed cracking and
      chipping. CONCLUSIONS: Edge-strength of flowable composites could be used to
      differentiate between materials and predict their clinical margin performance.
      Edge-fracture resistance of flowable composites is lower towards the margins than
      towards the centre of restoration.

PMID- 18068292
TI  - Endometriosis and the primary care consultation.
AB  - OBJECTIVES: Endometriosis is a long term, disabling condition, and a common cause
      of chronic pelvic pain. Symptomatic disease is usually characterised by pelvic
      and abdominal pain, lower back pain, and dyspareunia, all of which may be severe
      and debilitating. Yet the time between onset of symptoms and diagnosis is
      frequently a number of years, and many women report negative experience within
      the primary care setting. This paper explores the experience of women with
      endometriosis in the primary care setting. STUDY DESIGN: A qualitative research
      design was considered appropriate to elicit the experience of endometriosis and
      the impact on women's lives. Semi-structured interviews were conducted with 30
      women who suffer with endometriosis. The sample was recruited via a dedicated
      endometriosis clinic in the English Midlands, and participants had all been
      diagnosed laparoscopically with endometriosis. RESULTS: Participants described
      diverse experiences within the primary care setting. Although some women reported
      a positive relationship with their general practitioner, over half had had
      negative experiences, which they felt had contributed to delays in them receiving
      a diagnosis of endometriosis. CONCLUSION: The delay in diagnosis can be reduced
      and perceived attitudes of general practitioners towards women presenting with
      endometriosis can be improved by being alert to certain symptomology, and by
      detailed and sensitive history taking.

PMID- 18068290
TI  - Comparison of S-adenosyl-L-methionine (SAMe) and N-acetylcysteine (NAC)
      protective effects on hepatic damage when administered after acetaminophen
      overdose.
AB  - In the clinical setting, antidotes are generally administered after the
      occurrence of a drug overdose. Therefore, the most pertinent evaluation of any
      new agent should model human exposure. This study tested whether acetaminophen
      (APAP) hepatotoxicity was reversed when S-adenosyl-L-methionine (SAMe) was
      administered after APAP exposure, similar to what occurs in clinical situations.
      Comparisons were made for potency between SAMe and N-acetylcysteine (NAC), the
      current treatment for APAP toxicity. Male C57BL/6 mice were fasted overnight and
      divided into groups: control (VEH), SAMe treated (SAMe), APAP treated (APAP), N
      acetylcysteine treated (NAC), SAMe or NAC administered 1h after APAP (SAMe+APAP)
      and (NAC+APAP), respectively. Mice were injected intraperitoneal (i.p.) with
      water (VEH) or 250 mg/kg APAP (15 ml/kg). One hour later, mice were injected
      (i.p.) with 1.25 mmol/kg SAMe (SAMe+APAP) or NAC (NAC+APAP). Hepatotoxicity was
      evaluated 4h after APAP or VEH treatment. APAP induced centrilobular necrosis,
      increased liver weight and alanine transaminase (ALT) levels, depressed total
      hepatic glutathione (GSH), increased protein carbonyls and 4-hydroxynonenal (4
      HNE) adducted proteins. Treatment with SAMe 1h after APAP overdose (SAMe+APAP)
      was hepatoprotective and was comparable to NAC+APAP. Treatment with SAMe or NAC
      1h after APAP was sufficient to return total hepatic glutathione (GSH) to levels
      comparable to the VEH group. Western blot showed reversal of APAP mediated
      effects in the SAMe+APAP and NAC+APAP groups. In summary, SAMe was protective
      when given 1h after APAP and was comparable to NAC.

PMID- 18068293
TI  - A comparative study for the sorption of Cd(II) by soils with different clay
      contents and mineralogy and the recovery of Cd(II) using rhamnolipid
      biosurfactant.
AB  - Recent research has demonstrated that biosurfactants, especially rhamnolipids,
      can enhance recovery of soil-bound metals. To propose the success of remediation
      process of soils by rhamnolipids, both sorption and desorption characteristics of
      soils having different clay mineralogy should be known exactly. To assess
      sorption of Cd(II), batch equilibrium experiments were performed using three
      soils characterized with different proportions of clay minerals from Eskisehir
      region of Turkey. Soil pH, initial metal concentration and clay mineralogy
      affected the sorption process. For comparisons between soils, the sorption
      process was characterized using the Langmuir, Freundlich, Redlich-Peterson, Koble
      Corrigan sorption models. The Freundlich model showed the best fit for the Cd(II)
      sorption data by the soils, while the Langmuir-type models generally failed to
      describe the sorption data. Soils with higher clay content characterized by
      having smectite as a dominant component had the greatest sorption capacity and
      intensity estimated by the KF and n parameters of the Freundlich model. The soil
      C has the highest sorption efficiency of 83.9%, followed by soils B and A with
      sorption efficiencies of 76.7% and 57.9%, respectively. After the soils were
      loaded by different doses of Cd(II), batch washing experiments were used to
      evaluate the feasibility of using rhamnolipid biosurfactant for the recovery of
      Cd(II) from the soils. The Cd(II) recovery of the soils were investigated as a
      function of pH, amount of Cd(II) loaded to the soils, and rhamnolipid
      concentration. Cd(II) recovery efficiencies from the soils using rhamnolipid
      biosurfactant decreased in the order of soil A>soil B>soil C. This order was the
      reverse of the Cd(II) sorption efficiency order on the soils. When 80 mM
      rhamnolipid was used, the recovery efficiencies of Cd(II) from the soils A, B,
      and C was found to be 52.9%, 47.7%, 45.5% of the sorbed Cd(II), respectively.
      Rhamnolipid sorption capacity of the soils in the presence of Cd(II) ions
      decreased in the order of soil A>soil B>soil C.

PMID- 18068294
TI  - Degradation of 1-butyl-3-methylimidazolium chloride ionic liquid in a Fenton-like
      system.
AB  - The study examined the usefulness of a Fenton-like system for the degradation of
      ionic liquid residues in water. The ionic liquid was oxidized in a dilute aqueous
      solution of 1-butyl-3-methylimidazolium chloride (bmimCl). The ionic liquid
      decomposes readily and rapidly in aqueous solution by chemical degradation in a
      Fenton-like system. Under chosen conditions the initial bmimCl solution was
      reduced by a factor of 0.973 within 90 min. Additional results showed that bmimCl
      degradations in a Fenton-like system in excess H2O2 could be interpreted as a
      combined oxidation-reduction mechanism. Preliminary investigations of the
      mechanism of such degradations have indicated that initial OH* radicals can
      attack any one of the three carbon atoms on the imidazolium ring. The
      intermediates of this reaction may be mono- di- or amino- carboxylic acids.

PMID- 18068295
TI  - Error analysis of equilibrium studies for the almond shell activated carbon
      adsorption of Cr(VI) from aqueous solutions.
AB  - In this study, the preparation of activated carbon from almond shell with H2SO4
      activation and its ability to remove toxic hexavalent chromium from aqueous
      solutions are reported. The influences of several operating parameters such as
      pH, particle size and temperature on the adsorption capacity were investigated.
      Adsorption of Cr(VI) is found to be highly pH, particle size and temperature
      dependent. Four adsorption isotherm models namely, Langmuir, Freundlich, Tempkin
      and Dubinin-Radushkevich were used to analyze the equilibrium data. The Langmuir
      isotherm provided the best correlation for Cr(VI) onto the almond shell activated
      carbon (ASC). Adsorption capacity was calculated from the Langmuir isotherm as
      190.3 mg/g at 323 K. Thermodynamic parameters were evaluated and the adsorption
      was endothermic showing monolayer adsorption of Cr(VI). Five error functions were
      used to treat the equilibrium data using non-linear optimization techniques for
      evaluating the fit of the isotherm equations. The highest correlation for the
      isotherm equations in this system was obtained for the Freundlich isotherm. ASC
      is found to be inexpensive and effective adsorbent for removal of Cr(VI) from
      aqueous solutions.

PMID- 18068296
TI  - Manganese uptake and interactions with cadmium in the hyperaccumulator-
      Phytolacca Americana L.
AB  - In the present study, the accumulation of Mn and other metals by Phytolacca
      Americana L. from contaminated soils in Hunan Province, South China, was
      investigated. Results showed that the average concentrations of Mn in the leaves
      and roots reached 2198 and 80.4 mg kg(-1) (dry weight), respectively, with a
      maximum 13,400 mg kg(-1) in the leaves. A significant correlation was found
      between Mn concentrations in the plant leaves and those in the corresponding
      soils. Hydroponic experiments were also conducted to study the Cd uptake ability
      and interactions between Mn and Cd in the plant. It was found that P. americana
      hyperaccumulated not only Mn, but also Cd in the leaves. In the presence of Cd,
      adding Mn to the solution significantly improved the plant growth and reduced the
      concentrations of Cd in all organs of the plant.

PMID- 18068297
TI  - Numerical investigation of explosion suppression by inert particles in straight
      ducts.
AB  - This paper is devoted to the mitigation of explosions in long galleries by means
      of an inert dust cloud. In practice, this technique bases on mounting shelves
      under the roof, on which the inert dust is distributed. This issue was
      numerically investigated in this research. The medium was assumed to be a two
      phase mixture consisting of a fast flowing gas (representing the explosion) and a
      cloud of solid particles (representing the dust phase). The model makes use of
      the Eulerian-Lagrangian approach, where the solid particles are modelled as
      moving points, interacting with the gas flow. The objective was to analyse the
      suppression process and compare with experimental findings.

PMID- 18068298
TI  - Polychlorinated dibenzo-p-dioxins/dibenzofurans distributions in ash from
      different units in a municipal solid waste incinerator.
AB  - This study determined the polychlorinated dibenzo-p-dioxins/dibenzofurans
      (PCDD/Fs) contents in ash in the super heater (SH), economizer (EC), semi-dryer
      absorber (SDA), fabric filter (FF), fly ash pit (FAP) and bottom residue (BR) in
      a municipal solid waste incinerator (MSWI). A high-resolution gas
      chromatograph/high-resolution mass spectrometer (HRGC/HRMS) was utilized for
      analyzing 17 PCDD/F species. Experimental results showed that average PCDD/F
      contents in ash samples from the SH, EC, SDA, FF, FAP and BR were 0.102, 0.788,
      0.210, 1.95, 2.04 and 0.0218 ng I-TEQ g(-1), respectively. PCDD/F content was
      very low in the SH and BR due to high temperatures (around 461 degrees C in the
      SH and 914 degrees C in combustion chamber). Conversely, total PCDD/F content was
      significantly high in ash samples from the EC (around 340 degrees C), mainly
      because the temperature is within the favorable range of 250-400 degrees C for
      PCDD/F formation due to de nova reformation mechanisms. Although the SDA operated
      at 245 degrees C, the PCDD/F content decreased very significantly, mainly because
      the temperature was relatively low and because calcium carbonate was introduced
      into flue gases to dechlorinate and dilute chlorine-containing species. PCDD/Fs
      were captured by the active carbon in the FF. Furthermore, the duration that fly
      ash remained in the FF was longer than that for other incinerator units, and thus
      causing an increasing trend of PCDD/Fs level downstream (except the SDA). Total
      PCDD/Fs emission factors (microg tonnes-waste(-1); microg I-TEQ tonnes-waste(-1))
      in ash samples from different units were: SH (42.3; 0.846), EC (326; 6.12), SDA
      (58.1; 1.10), FF (1540; 61.3), FAP (2950; 107) and BR (537; 4.31). Most PCDD/Fs
      in ash were contributed by the FF (about 56%), and the generation of PCDD/Fs in
      ash was significant (about 35%) during the transfer process from different units
      to the FAP. A strong and positive correlation in a logarithmic form existed
      between PCDD/Fs and chlorine (Cl(-1)) contents in ash. In Taiwan, the government
      policy for incineration residues advocates their reuse as road sub-bases or
      secondary building materials provided that total PCDD/Fs content is below the
      legal limit (1 ng I-TEQ g(-1)). Thus, ash with total PCDD/Fs content below the
      legal limit, such as that from the SH, EC, SDA and BR, can be collected and
      transferred to the FAP and reused. Ash with total PCDD/Fs content exceeding the
      legal limit, such as that from the FF, should be collected separately and be
      treated properly before being disposal in a landfill.

PMID- 18068299
TI  - Assessment of Pb-slag, MSWI bottom ash and boiler and fly ash for using as a fine
      aggregate in cement mortar.
AB  - Three types of wastes, metallurgical slag from Pb production (SLG), the sand
      sized (0.1-2 mm) fraction of MSWI bottom ash from a grate furnace (SF), and
      boiler and fly ash from a fluidised bed incinerator (BFA), were characterized and
      used to replace the fine aggregate during preparation of cement mortar. The
      chemical and mineralogical behaviour of these wastes along with the reactivities
      of the wastes with lime and the hydration behaviour of ordinary Portland cement
      paste with and without these wastes added were evaluated by various chemical and
      instrumental techniques. The compressive strengths of the cement mortars
      containing waste as a partial substitution of fine aggregates were also assessed.
      Finally, leaching studies of the wastes and waste containing cement mortars were
      conducted. SLG addition does not show any adverse affect during the hydration of
      cement, or on the compressive strengths behaviours of mortars. Formation of
      expansive products like ettringite, aluminium hydroxide and H2 gas due to the
      reaction of some constituents of BFA and SF with alkali creates some cracks in
      the paste as well as in the cement mortars, which lower the compressive strength
      of the cement mortars. However, utilization of all materials in cement-based
      application significantly improves the leaching behaviour of the majority of the
      toxic elements compared to the waste as such.

PMID- 18068300
TI  - Comparison of cytokine expression profile during Wallerian degeneration of
      myelinated and unmyelinated peripheral axons.
AB  - Changes in cytokine and chemokine expression during Wallerian degeneration have
      been studied using nerve transection models, which result in denervation of both
      myelinating and non-myelinating Schwann cells. Cytokine and chemokine response of
      non-myelinating Remak Schwann cells to loss of their axons is unknown. In this
      study, we compared the expression profile of various cytokines and chemokines in
      distal nerves after capsaicin-induced degeneration of unmyelinated axons to
      Wallerian degeneration induced by nerve transection. Upregulation of MCP-1, IL-2,
      IL-6 and IL-10 were seen in both groups but IL-1ss and LIF were primarily
      upregulated in Wallerian degeneration of the whole nerve and not in capsaicin
      induced degeneration of unmyelinated axons. The activated macrophage response, as
      measured by an increase in ED-1 immunostaining, was more prominent in the
      transected sciatic nerves compared to capsaicin-treated nerves. These findings
      indicate that there are differences in the cytokine and chemokine response of
      myelinating and non-myelinating Schwann cells to loss of their axons, and add to
      a growing body of literature that points to greater heterogeneity among Schwann
      cells.

PMID- 18068301
TI  - Mutation analysis of the parkin and PINK1 genes in American Caucasian early-onset
      Parkinson disease families.
AB  - Mutations in the parkin gene and the PTEN-induced putative kinase 1 gene (PINK1)
      have been identified as the most common causes of autosomal recessive early-onset
      Parkinson disease (EOPD). To investigate the presence of the parkin and PINK1
      gene mutation(s) and to explore genotype-phenotype correlations in American
      Caucasian families with EOPD from North American, we screened these two genes in
      probands of six families by direct sequencing, semi-quantitative PCR and RT-PCR.
      No PINK1 gene mutation was found in any of the probands, but compound
      heterozygous mutations (EX 3 del and EX 3_4 del) in the parkin gene were
      identified in one family. Extended analysis of the parkin-positive family showed
      the phenotype of patients was that of classic autosomal recessive EOPD,
      characterized by early age at onset, slow progression, beneficial response to
      levodopa, and levodopa-related motor complications. Three heterozygous mutation
      carriers (EX 3 del or EX 3_4 del) were free of any neurological symptoms. None of
      62 healthy controls harbored EX 3 del or EX 3_4 del mutation. Our data suggest
      that compound heterozygous mutations (EX 3 and EX 3_4 del) in the parkin gene
      were the cause of EOPD in one of six Caucasian families; heterozygous EX 3 del
      and heterozygous EX 3_4 del forms were insufficient to cause this disorder,
      consistent with a loss-of-function mechanism of the parkin mutations. The results
      may provide new insights into the cause and diagnosis of PD and have implications
      for genetic counseling.

PMID- 18068302
TI  - Neurotransplantation in mice: the concorde-like position ensures minimal cell
      leakage and widespread distribution of cells transplanted into the cisterna
      magna.
AB  - The access of transplanted cells to large areas of the CNS is of critical value
      for cell therapy of chronic diseases associated with widespread
      neurodegeneration. Intrathecal cell application can match this requirement. Here
      we describe an efficient method for cell injection into the cisterna magna and
      the assessment of the cell distribution within subarachnoidal space in mice. In
      order to maximize cell distribution we applied a "concord-like" position, where
      the cisterna magna is nearly the highest point of the animal's body. A drop of
      saline on the needle insertion site avoided the outflow of transplanted cells
      from subarachnoidal space with CSF during surgery. Twenty-four hours later the
      preparation of the CNS with an intact dura mater by a suitable dissection
      technique (described in detail) revealed approx. 80% of the injected cells
      (100,000 cells per animal) within the subarachnoidal space ranging from the skull
      base (olfactory nerve to premedullary cisterns) to the IV ventricle, and to both
      the ventral and dorsal surfaces of the spinal cord. Thus the "concorde-like"
      position proved to be very useful for intrathecal cell application leading to a
      widespread cell distribution within the subarachnoidal space.

PMID- 18068303
TI  - Imaging of intracellular spherical lamellar structures and tissue gross
      morphology by a focused ion beam/scanning electron microscope (FIB/SEM).
AB  - We report the use of a focused ion beam/scanning electron microscope (FIB/SEM)
      for simultaneous investigation of digestive gland epithelium gross morphology and
      ultrastructure of multilamellar intracellular structures. Digestive glands of a
      terrestrial isopod (Porcellio scaber, Isopoda, Crustacea) were examined by
      FIB/SEM and by transmission electron microscopy (TEM). The results obtained by
      FIB/SEM and by TEM are comparable and complementary. The FIB/SEM shows the same
      ultrastructural complexity of multilamellar intracellular structures as indicated
      by TEM. The term lamellar bodies was used for the multillamellar structures in
      the digestive glands of P. scaber due to their structural similarity to the
      lamellar bodies found in vertebrate lungs. Lamellar bodies in digestive glands of
      different animals vary in their abundance, and number as well as the thickness of
      concentric lamellae per lamellar body. FIB/SEM revealed a connection between
      digestive gland gross morphological features and the structure of lamellar
      bodies. Serial slicing and imaging of cells enables easy identification of the
      contact between a lamellar body and a lipid droplet. There are frequent reports
      of multilamellar intracellular structures in different vertebrate as well as
      invertebrate cells, but laminated cellular structures are still poorly known. The
      FIB/SEM can significantly contribute to the structural knowledge and is always
      recommended when a link between gross morphology and ultrastructure is
      investigated, especially when cells or cellular inclusions have a dynamic nature
      due to normal, stressed or pathological conditions.

PMID- 18068304
TI  - Temperature dependence of NR1/NR2B NMDA receptor channels.
AB  - N-methyl-D-aspartate (NMDA) receptors are highly expressed in the CNS, mediate
      the slow component of excitatory transmission and play key roles in synaptic
      plasticity and excitotoxicity. These ligand-gated ion channels are
      heteromultimers composed of NR1 and NR2 subunits activated by glycine and
      glutamate. In this study, patch-clamp recordings were used to study the
      temperature sensitivity of recombinant NR1/NR2B receptors expressed in human
      embryonic kidney (HEK) 293 cells. Rate constants were assessed by fitting a six
      state kinetic scheme to time courses of transient macroscopic currents induced by
      glutamate at 21.9-46.5 degrees C. Arrhenius transformation of the rate constants
      characterizing NMDA receptor channel activity indicates that the most sensitive
      were the rate constants of desensitization (temperature coefficient Q(10)=10.3),
      resensitization (Q(10)=4.6) and unbinding (Q(10)=3.6). Other rate constants and
      the amplitude of single-channel currents were less temperature sensitive.
      Deactivation of responses mediated by NR1/NR2B receptors after a brief
      application of glutamate was best fit by a double exponential function
      (tau(fast): Q(10)=3.7; tau(slow): Q(10)=2.7). From these data, we conclude that
      desensitization/resensitization of the NMDA receptor and glutamate unbinding are
      especially temperature sensitive and imply that at physiological temperatures the
      channel kinetics play an important role in determining amplitude and time course
      of NMDA receptor-mediated postsynaptic currents and these receptors mediated
      synaptic plasticity.

PMID- 18068305
TI  - Glial expression of cannabinoid CB(2) receptors and fatty acid amide hydrolase
      are beta amyloid-linked events in Down's syndrome.
AB  - Recent data suggest that the endocannabinoid system (ECS) may be involved in the
      glial response in different types of brain injury. Both acute and chronic insults
      seem to trigger a shift in the pattern of expression of some elements of this
      system from neuronal to glial. Specifically, data obtained in human brain tissue
      sections from Alzheimer's disease patients showed that the expression of
      cannabinoid receptors of the CB(2) type is induced in activated microglial cells
      while fatty acid amide hydrolase (FAAH) expression is increased in reactive
      astrocytes. The present study was designed to determine the time-course of the
      shift from neuronal to glial induction in the expression of these proteins in
      Down's syndrome, sometimes referred to as a human model of Alzheimer-like beta
      amyloid (Abeta) deposition. Here we present immunohistochemical evidence that
      both CB(2) receptors and FAAH enzyme are induced in Abeta plaque-associated
      microglia and astroglia, respectively, in Down's syndrome. These results suggest
      that the induction of these elements of the ECS contributes to, or is a result
      of, amyloid deposition and subsequent plaque formation. In addition, they confirm
      a striking differential pattern of distribution of FAAH and CB(2) receptors.

PMID- 18068306
TI  - Longitudinal neuroendocrine changes assessed by dexamethasone/CRH and growth
      hormone releasing hormone tests in psychotic depression.
AB  - Although psychotic depression has been reported to exhibit a greater degree of
      dysregulation of hypothalamic-pituitary-adrenocortical (HPA) function than non
      psychotic depression, little is known concerning hypothalamic-pituitary
      somatotropic (HPS) function in psychotic depression and how neuroendocrine
      function changes after treatment. To investigate the longitudinal changes in HPA
      and HPS system function in psychotic depression, we performed repeated
      dexamethasone/corticotropin releasing hormone (DEX/CRH) tests and growth hormone
      (GH) releasing hormone (GHRH) tests in inpatients with major depressive disorder.
      The psychotic depression group exhibited greater elevation of ACTH responses to
      the DEX/CRH test and stronger decreases in GH responses to the GHRH test than the
      non-psychotic depression group at admission. At discharge, the neuroendocrine
      responses to the DEX/CRH test of the psychotic depression group were still
      stronger than those of the non-psychotic depression group, though there were no
      significant differences in severity of depression between the groups. There were
      significant longitudinal changes in neuroendocrine responses to the DEX/CRH test
      between admission and discharge. The psychotic depression group exhibited
      increased GH responses to GHRH at discharge compared with those at admission,
      whereas no significant longitudinal change in GH response was found in the non
      psychotic depression group. Consequently, there were no significant differences
      in GH responses to GHRH between the psychotic and non-psychotic depression groups
      at discharge. The results of GHRH test showed no significant relationships with
      severity of depression except psychotic features and the results of the DEX/CRH
      test. Our findings suggest that the HPS axis may be associated with psychotic
      features rather than general severity of depression. Further longitudinal studies
      are needed to clarify the role of HPS function in psychotic depression and
      whether sustained dysregulation of HPA function in psychotic depression is
      associated with a poor outcome after discharge.

PMID- 18068307
TI  - Perceptions of level of intoxication and risk related to drinking and driving.
AB  - This study investigated variables of perceived risk associated with one's
      decision to drink and drive, as well as with the occurrence and successfulness of
      intervention efforts by others in preventing individuals from drinking and
      driving. Undergraduate students were presented with scenarios manipulating number
      of drinks, consumption time, and distance needed to drive. Participants then
      provided estimates of intoxication, degree of impairment, and likelihood of
      getting in an accident and getting arrested for drinking and driving. In
      addition, participants rated three criterion variables: intention to drive,
      likelihood someone would try to intervene, and receptiveness to someone
      attempting to intervene. Data was analyzed using three random effects regression
      models, one for each of the criterion variables. Results indicated that
      perceptions of risk were associated with decisions to drive after drinking and
      expected likelihood of, and receptiveness to, intervention efforts, over and
      above one's estimate of intoxication.

PMID- 18068308
TI  - Assessment of perceived and actual alcohol norms in varying contexts: exploring
      Social Impact Theory among college students.
AB  - The social norms approach to college drinking suggests that students misperceive
      the drinking behavior and attitudes of their peers. While much is known about
      these misperceptions, research is sparse regarding the context in which perceived
      and actual norms are assessed. As social influence is pronounced in college, the
      principles of Social Impact Theory may contribute to differences between
      assessments performed individually and those completed when surrounded by members
      of one's salient reference group. The current study examines 284 members of
      campus organizations in two contexts (online and group) to determine if
      individuals endorse different responses to questions of perceived and actual
      drinking norms across contexts. All participants endorsed higher responses on
      questions of actual and perceived group behavior and of perceived group attitudes
      towards drinking during the group assessment. Men and students in Greek
      organizations may be more influenced by the proximity of their peers when
      presented with questions regarding perceived alcohol use. These results suggest
      that context of assessment needs to be considered when collecting self-report
      data from college students.

PMID- 18068309
TI  - Evolutional pattern of drug use by medical students.
AB  - Recent use of psychoactive substances among 456 medical students throughout the
      six grades was surveyed by way of a self-report questionnaire using World Health
      Organisation criteria. Among male medical students, the most frequently used
      substances were alcohol (80.5%), cannabis (25.3%), solvents (25.2%), and tobacco
      (25.2%), whereas among female students the most frequently used drugs were
      alcohol (72.6%), tobacco (14.6%), solvents (10.5%), and tranquillizers (7.5%).
      Switch from illegal to legal drugs were observed only among female medical
      students. Male students tend to alternate cannabis and solvents throughout
      college years. Interventions aiming to influence patterns of drug consumption
      among medical students must consider both gender differences and evolutional
      patterns of substance use throughout medical course.

PMID- 18068310
TI  - Postoperative spot-scanning proton radiation therapy for chordoma and
      chondrosarcoma in children and adolescents: initial experience at paul scherrer
      institute.
AB  - PURPOSE: To evaluate postoperative spot-scanning proton radiation therapy (PT)
      and intensity-modulated PT (IMPT) for chordoma and chondrosarcoma in pediatric
      patients. METHODS AND MATERIALS: Between 2000 and 2005, 10 patients (six male
      patients, four female patients; six chordomas, four chondrosarcomas), aged 10-20
      years (median, 16 years), were treated at our institute. Tumor sites were in the
      brain (one case), skull base (five cases), cervical (three cases), and lumbar
      spine (one case). Three children had complete resections. In seven children,
      resection was incomplete, leaving residual tumor behind (range, 2.3-46.3 mL). PT
      was delivered using spot scanning, with (three patients) or without (seven
      patients) IMPT. Total dose was 74.0 cobalt Gray equivalents (CGE) for chordoma,
      and 63.2-68.0 CGE for chondrosarcoma (median, 66.0), depending on
      histopathological grading and whether the patient had concurrent chemotherapy.
      RESULTS: Median follow-up time was 36 months (range, 8-77 months). Radiation
      treatment was well tolerated. All patients remained failure-free at their last
      follow-up. Late adverse events were reported in three patients and were mild
      (neurosensory in one patient; alopecia and hypoaccusis in one patient) to
      moderate (one patient, Grade 2 pituitary insufficiency). CONCLUSIONS:
      Postoperative spot-scanning PT, delivered in combination with and without IMPT,
      for chordoma and chondrosarcoma in children and adolescents was tolerated without
      unacceptable adverse event and initial outcome is perfectly satisfactory in this
      small cohort. Longer follow-up time and larger cohort are needed to more fully
      assess tumor control, adverse events, as well as functional and cosmetic outcome.

PMID- 18068311
TI  - Long-term outcomes for desmoid tumors treated with radiation therapy.
AB  - PURPOSE: To evaluate long-term outcomes in patients with desmoid fibromatosis
      treated with radiation therapy (RT), with or without surgery. METHODS AND
      MATERIALS: Between 1965 and 2005, 115 patients with desmoid tumors were treated
      with RT at our institution. The median age was 29 years (range, 8-73 years). Of
      the patients, 41 (36%) received RT alone (median dose, 56 Gy) for gross disease,
      and 74 (64%) received combined-modality treatment (CMT) consisting of a
      combination of surgery and RT (median dose, 50.4 Gy). RESULTS: Median follow-up
      was 10.1 years. Local control (LC) rates at 5 and 10 years were 75% and 74%,
      respectively. On univariate analysis, LC was significantly influenced by tumor
      size (< or =5 cm vs. 5-10 cm vs. >10 cm) (p = 0.02) and age (< or = 30 vs. >30
      years) (p = 0.02). There was no significant difference in LC for patients treated
      with RT alone for gross disease vs. CMT. For patients treated with CMT, only
      tumor size significantly influenced LC (p = 0.02). Patients with positive margins
      after surgery did not have poorer LC than those with negative margins (p = 0.38).
      Radiation-related complications occurred in 20 (17%) of patients and were
      associated with dose >56 Gy (p = 0.001), age < or =30 years (p = 0.009), and
      receipt of RT alone vs. CMT (p = 0.01). CONCLUSIONS: Desmoid tumors are
      effectively controlled with RT administered either as an adjuvant to surgery when
      resection margins are positive or alone for gross disease when surgical resection
      is not feasible. Doses >56 Gy may not be necessary to control gross disease and
      are associated with high rates of radiation-related complications.

PMID- 18068312
TI  - [Emergency caesarean delivery: is there an ideal decision-to-delivery interval?].
AB  - BACKGROUND: Among data on medical liability for obstetrical practice in labour
      ward, one of the claims concerns the decision-to-delivery interval during
      emergency caesarean section, for which an optimal time is frequently advocated. A
      realistic review on this subject is needed. LITERATURE REVIEW: It mainly allows
      to note that: unlike current opinion, neonatal prognosis is more dependent on the
      causal pathology than on decision-to-delivery interval; the transfer time to the
      operating theater, which represents approximately half of this interval, should
      benefit an internal audit for each maternity as it is mainly dependent on
      organization and architectural specifications; the choice of mode of anesthesia
      in relation with the obstetrical context and the induction time have a strong
      incidence, which shows the importance of a good communication between the
      obstetrician and the anesthetist. CONCLUSION: A detailed analysis of obstetrical
      context and of each sequence of the decision-to-delivery interval is more
      efficient and realistic for evaluation in medical liability cases than an optimal
      "gold standard". In addition, it allows a prophylactic reflexion for a risk
      management approach in each labour ward.

PMID- 18068313
TI  - Image scoring in great apes.
AB  - 'Image scoring' occurs when person A monitors the giving behaviour of person B
      towards person C. We tested for 'image scoring' in chimpanzees, bonobos,
      gorillas, and orangutans. Subjects passively observed two types of incident: (i)
      a 'nice' person gave grapes to a human beggar, and (ii) a 'nasty' person refused
      to give. The subject witnessed both incidents in succession (but was unable to
      obtain the grapes). Shortly after, the ape had an opportunity to approach one or
      both human actors (nice/nasty), both of whom were now sitting side-by-side
      holding grapes. However, neither human offered their grapes if approached. The
      subject's expectation of which human was more likely to offer food was measured
      by comparing the proportion of time that subjects spent near each person.
      Chimpanzees (n=17) spent significantly more time at the 'nice' window compared to
      'nasty'. Also, preference for 'nasty' declined as trials progressed. Results for
      other apes were not significant.

PMID- 18068315
TI  - Allelic loss and mutations in a new ETRG-1 gene are early events in
      diethylstilbestrol-induced renal carcinogenesis in Syrian hamsters.
AB  - Diethylstilbestrol (DES) is a synthetic estrogen and well known human carcinogen,
      but the mechanism by which DES causes cancer is not clear. In this study, using
      AP-PCR method we have identified a genetic alteration that was common in DES
      induced kidney tumors as well as in its surrounding non-tumor tissue. Further
      characterization of this genetically altered region revealed that it represents
      an uncharacterized novel gene. We have named this gene as Estrogen Target Rodent
      Gene-1 (ETRG-1). Southern blot analysis revealed about 50% reduction in the ETRG
      1 gene-specific hybridization signal, indicating genomic loss of one allele of
      ETRG-1 in DES-induced tumors as compared to its age-matched control. Sequence
      analysis of the remaining allele of ETRG-1 from tumor revealed point mutations
      and an insertion of 37 bp as compared to its normal allele from the age-matched
      control kidney tissue. The expression of ETRG-1 at transcript level was found to
      be extremely reduced or undetectable in DES-induced kidney tumors as compared to
      its age-matched control kidney tissue. Thus, the findings of this study suggest
      that (a) DES-induced allelic loss and mutations may be involved in DES-induced
      kidney carcinogenesis, (b) Constitutive expression of ETRG-1 in normal kidney
      tissue and decreased or undetectable expression in tumors, presumably as a result
      of allelic loss and mutational inactivation, suggest that it may be a tumor
      suppressor gene, and finally, (c) The identification of the allelic loss and
      mutations that were common in DES-exposed non-tumor kidney tissue, and in frank
      kidney tumors indicate that these genetic aberrations are early events in DES
      induced kidney carcinogenesis and it may serve as biomarker for early detection
      of DES-induced cancer.

PMID- 18068314
TI  - Do adolescent ecstasy users have different attitudes towards drugs when compared
      to marijuana users?
AB  - BACKGROUND: Perceived risk and attitudes about the consequences of drug use,
      perceptions of others expectations and self-efficacy influence the intent to try
      drugs and continue drug use once use has started. We examine associations between
      adolescents' attitudes and beliefs towards ecstasy use; because most ecstasy
      users have a history of marijuana use, we estimate the association for three
      groups of adolescents: non-marijuana/ecstasy users, marijuana users (used
      marijuana at least once but never used ecstasy) and ecstasy users (used ecstasy
      at least once). METHODS: Data from 5049 adolescents aged 12-18 years old who had
      complete weighted data information in Round 2 of the Restricted Use Files (RUF)
      of the National Survey of Parents and Youth (NSPY). Data were analyzed using
      jackknife weighted multinomial logistic regression models. RESULTS: Adolescent
      marijuana and ecstasy users were more likely to approve of marijuana and ecstasy
      use as compared to non-drug using youth. Adolescent marijuana and ecstasy users
      were more likely to have close friends who approved of ecstasy as compared to non
      drug using youth. The magnitudes of these two associations were stronger for
      ecstasy use than for marijuana use in the final adjusted model. Our final
      adjusted model shows that approval of marijuana and ecstasy use was more strongly
      associated with marijuana and ecstasy use in adolescence than perceived risk in
      using both drugs. CONCLUSION: Information about the risks and consequences of
      ecstasy use need to be presented to adolescents in order to attempt to reduce
      adolescents' approval of ecstasy use as well as ecstasy experimentation.

PMID- 18068316
TI  - Comparative evaluation of virulence and pathology of Streptococcus suis serotypes
      2 and 9 in experimentally infected growers.
AB  - Streptococcus (S.) suis is an invasive porcine pathogen causing meningitis,
      septicemia, arthritis and other diseases. Studies on pathogenesis as well as
      vaccine trials have focused on serotype 2 strains, which are worldwide the most
      prevalent among invasive isolates. However, in Europe serotype 9 strains also
      contribute substantially to S. suis-associated invasive diseases of piglets. The
      objective of this study was to determine the virulence of an MRP* SLY+ serotype 9
      S. suis strain in comparison to an MRP+ EF+ SLY+ serotype 2 strain. Experimental
      intranasal and intravenous infections of 7-8 weeks old SPF piglets were
      investigated with regard to clinic and pathology. In contrast to the virulent
      serotype 2 strain, the serotype 9 strain did not cause disease with clinical
      manifestations after intranasal administration. However, histological screenings
      of these animals revealed pathological lesions, such as mild focal suppurative
      meningitis. Clinical manifestations related to meningitis, arthritis and
      serositis could be induced by intravenous application of this serotype 9 strain.
      Bacteriological culture and immunohistochemistry of the brain confirmed
      association with the S. suis challenge strains in all cases with clinical
      manifestations. Interestingly, expression of MRP within meningitis lesions was
      demonstrated for both pathotypes via immunohistochemistry. In conclusion, this
      study demonstrates that MRP* SLY+ serotype 9 strains are less virulent for
      growers than MRP+ EF+ SLY+ serotype 2 strains. Thus, intravenous application of
      this serotype 9 strain is required to evaluate heterologous protection in the
      course of vaccine development based on serotype 2 strains in the future.

PMID- 18068317
TI  - Exposure-triggered reproductive toxicity testing under the REACH legislation: a
      proposal to define significant/relevant exposure.
AB  - Under the new REACH legislation, toxicological testing is required in relation to
      annual tonnages produced or imported. Requirements for toxicological information
      increase when production volume increases. The respective information
      requirements are laid down in the REACH Annexes VII-X. Concerning human
      toxicology, certain toxicological tests may be waived under specific conditions.
      Aside from waiving criteria such as technical feasibility, exposure plays a
      decisive role in the waiving process with the consequence that toxicological
      testing will not be required in case of "no relevant exposure", "limited
      exposure", "no exposure" or "no significant exposure" (as expressed in the
      documents). However, up to now criteria are lacking which precisely define these
      terms. Attempts have been made to establish cut-off criteria between "non
      relevant" and "relevant" (detrimental) exposure based on external exposure
      concentrations and the threshold of toxicological concern (TTC) principle. In
      this paper we make a proposal and describe a strategy how to define the currently
      insufficiently described terms "relevant/significant" exposure. We propose to
      define relevant/significant exposure based on an endpoint-specific TTC approach,
      starting from a comparison of the tentative external exposure to the specific
      TTC. This can be followed by a refinement of exposure estimates and may culminate
      in the experimental determination of internal and target tissue exposure. This
      strategy enables a well-founded assessment of what "no relevant exposure" is and
      safeguards an appropriate level of protection of the general population. The
      feasibility of the approach is demonstrated for reproductive toxicity endpoints.

PMID- 18068318
TI  - Mechanism of the photochemical degradation of amlodipine.
AB  - A mechanistic investigation on the photodegradation of amlodipine, the
      corresponding besylate and a simple analogue lacking the beta-aminoethoxy group
      has been carried out in water and in organic solvents. Irradiation leads to
      aromatization to the corresponding pyridines through an oxygen-independent
      process. The quantum yield for amlodipine base is Phi congruent with 0.001 under
      UV-A light, about one order of magnitude larger than that for the model bearing
      no amino group, supporting intramolecular assistance by that group. The value of
      Phi increases up to ca. 0.01 at shorter wavelength. The photolability of this
      drug according to ICH criteria is justified by the high absorptivity in the UV-A
      range (epsilon(UV-A)), despite the low quantum yield. Some comments are added
      about the fact that product Phi x epsilon(UV-A) is more significative than Phi
      alone for the photolability (in solution) and about the lacking possibility to
      quench the photoreactivity where, as in the present case, this involves only
      short-lived intermediates.

PMID- 18068319
TI  - Mechanistic analysis of pH-dependent solubility and trans-membrane permeability
      of amphoteric compounds: application to sildenafil.
AB  - This study was aimed at investigating the pH-dependent solubility and in vitro
      transmucosal permeability of sildenafil, an amphoteric compound with limited
      aqueous solubility, across parallel artificial membrane. The aqueous solubility
      and permeability of sildenafil as a function of solution pH were theoretically
      derived from the individual contributions of all species (cationic, neutral and
      anionic). The stability, octanol-water distribution coefficient (log D), and
      solubility of sildenafil were then determined at various pHs, the permeability
      study was also performed at different pHs using parallel artificial membrane. The
      pH-solubility and -permeability profiles were then fitted to theoretical
      equations using non-linear regression. The experimental pH-solubility profile was
      fitted very well to the theoretical equations (R(2)=0.9996). The in vitro
      permeability of saturated sildenafil solution at different pH values also showed
      similar trend as the predicted one (R(2)=0.7829). The two optimum pH (pH(max))
      values were found to be 4.50 and 10.24, where the maximum solubility of either
      cationic or neutral species, or anionic and neutral species is simultaneously
      obtained, and the maximal transmucosal fluxes (J(ss)) are achieved. The above
      method can be applied to optimize the transmucosal delivery of other amphoteric
      drugs with low aqueous solubility.

PMID- 18068321
TI  - An important item in these studies is the definition of the reference standard.

PMID- 18068320
TI  - Antiprotozoal and cytotoxic screening of 45 plant extracts from Democratic
      Republic of Congo.
AB  - AIM OF THE STUDY: To evaluate in vitro the antiprotozoal and cytotoxic activities
      of 80% methanol extract from 45 medicinal plants collected in Sankuru (Democratic
      Republic of Congo) against Trypanosoma brucei brucei, Trypanosoma cruzi and the
      chloroquine-sensitive Ghanaian strain of Plasmodium falciparum, and MRC-5 cell
      lines respectively. MATERIAL AND METHODS: Different extracts were obtained by
      maceration of each plant part used with 80% methanol for 24h. The mixture was
      filtered and evaporated in vacuo to give corresponding dried extract. The
      activity against Trypanosoma brucei brucei and Trypanosoma cruzi were performed
      in 96 well tissue plates each containing 10 microl aqueous plant extract
      dilutions (100 to 0.01 microg/ml) with 10 microl of the parasite suspension
      cultured in Hirumi medium supplemented with 10% foetal calf serum, a solution of
      2% penicillin/streptomycin (2% P/S) After 4 days incubation with Almar bluea
      solution, fluorescence was measured at 500 nm emission and 530 nm excitation and
      results expressed as percentage reduction in parasite compared to control wells.
      The antiplasmodial activity of was assessed in vitro against the chloroquine
      sensitive Ghanaian strain of Plasmodium falciparum cultured in RPMI-1640 medium
      by the lactate deshydrogenase assay in the presence of plant extracts (50 to 0.01
      microg/ml). Cell-lines MRC-5 were cultured in MEM medium supplemented with 20mM l
      glutamine, 16.5mM NaHCO(3), 5% foetal calf serum and 2% P/S solution. After 4h
      incubation, cell proliferation/viability was spectrophotomecally assessed at 540
      nm after addition of MTT. In each assay, the IC50 value for each sample was
      derived by the drug concentration-response curves. RESULTS: The extracts from
      Alcornea cordifolia leaves, Momordica charantia whole plant, Omphalocarpum
      glomerata, root bark and Piptadia africanum stem bark showed good antiprotozoal
      activity against Trypanosoma brucei brucei with IC50 values from 0.7 to 7
      microg/ml. Only Piptadenia africanum extract showed a pronounced antiprotozoal
      activity against Trypanosoma cruzi (IC50=4.0+/-06 microg/ml). The extracts from
      Alchornea cordifolia, Polyathia swaveleons stem bark, Sapium cornutum stem bark
      and Triclisia giletii stem bark exhibited a pronounced antiplasmodial activity
      against P. falciparum Ghanaian strain with IC50 values ranging from 0.5 to 3.0
      microg/ml. Piptadenia africanum extract was the most cytotoxic sample (CC50=0.25
      microg/ml) with poor selectivity against all selected protozoa (SI<10) while
      other active extracts did not show a significant cytotoxic effect against MCR-5
      cell-lines with good selectivity according to the case. CONCLUSION: These active
      plant extracts are selected for extensive studies leading to the isolation of
      active constituents.

PMID- 18068322
TI  - The thyroid dose burden in medical imaging A re-examination.
AB  - Radiation is the best defined causative factor in thyroid cancer. The thyroid is
      especially susceptible to injury from radiation to which it may be exposed in a
      variety of circumstances in addition to natural background: radiotherapy,
      including, historically, therapy of such benign conditions as ring worm and
      haemangiomata, radiation exposure in nuclear accidents and fallout from nuclear
      bomb tests, and diagnostic exposures, particularly in the relatively high dose CT
      examination of head and neck. Both use of CT and the incidence of thyroid cancer
      appear to be increasing worldwide and it has been suggested that there may be a
      causative relationship between the two. It has been further posited that the
      iodine content of the thyroid might play a role in increasing the radiation dose
      absorption. Indeed, on the same basis, iodine administered in the form of an X
      ray contrast-enhancing agent might also be expected to play some role in
      increasing thyroid radiation absorption resulting in a yet higher dose burden in
      any give circumstances than is generally assumed. In view of the importance of
      these ideas we have performed some calculations to estimate the magnitude of the
      iodine effects. We conclude that they are not great enough to cause concern.

PMID- 18068323
TI  - Determination of total polyphenols content in green tea using FT-NIR spectroscopy
      and different PLS algorithms.
AB  - This paper attempted the feasibility to determine content total polyphenols
      content in green tea with near infrared (NIR) spectroscopy coupled with an
      appropriate multivariate calibration method. Partial least squares (PLS),
      interval PLS (iPLS) and synergy interval PLS (siPLS) algorithms were performed
      comparatively to calibrate regression model. The number of PLS components and the
      number of intervals were optimized according to root mean square error of cross
      validation (RMSECV) in calibration set. The performance of the final model was
      evaluated according to root mean square error of prediction (RMSEP) and
      correlation coefficient (R) in prediction set. Experimental results showed that
      the performance of siPLS model is the best in contrast to PLS and iPLS. The
      optimal model was achieved with R=0.9583 and RMSEP=0.7327 in prediction set. This
      study demonstrated that NIR spectroscopy with siPLS algorithm could be used
      successfully to analysis of total polyphenols content in green tea, and revealed
      superiority of siPLS algorithm in contrast with other multivariate calibration
      methods.

PMID- 18068324
TI  - Quantitative analysis of polypeptide pharmaceuticals by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - An accurate method based on matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF-MS) has been developed for quantitative
      analysis of calcitonin and insulin in different commercially available
      pharmaceutical products. Tryptic peptides derived from these polypeptides were
      chemically modified at their C-terminal lysine-residues with 2-methoxy-4,5
      dihydro-imidazole (light tagging) as standard and deuterated 2-methoxy-4,5
      dihydro-imidazole (heavy tagging) as internal standard (IS). The heavy modified
      tryptic peptides (4D-Lys tag), differed by four atomic mass units from the
      corresponding light labelled counterparts (4H-Lys tag). The normalized peak areas
      (the ratio between the light and heavy tagged peptides) were used to construct a
      standard curve to determine the concentration of the analytes. The concentrations
      of calcitonin and insulin content of the analyzed pharmaceutical products were
      accurately determined, and less than 5% error was obtained between the present
      method and the manufacturer specified values. It was also found that the cysteine
      residues in CSNLSTCVLGK from tryptic calcitonin were converted to lanthionine by
      the loss of one sulfhydryl group during the labelling procedure.

PMID- 18068325
TI  - Genotypes of macrolide-resistant pneumococci from children in southwestern Japan:
      raised incidence of strains that have both erm(B) and mef(A) with serotype 6B
      clones.
AB  - MICs of penicillin G, erythromycin, clarithromycin, clindamycin, azithromycin,
      and telithromycin were tested for 189 clinical isolates collected during 2002 to
      2005 from children in southwestern Japan. Serotyping and polymerase chain
      reaction for presence of erm(B) and mef(A) were performed. All strains with
      erm(B) + mef(A) were analyzed by pulsed-field gel electrophoresis (PFGE) and
      compared to 3 global clones: Spain(23F)-1; Spain(9V)-3 and its variant -14; a
      South Korean strain same as Taiwan (19F)-14 clone and 5 strains with erm(B) +
      mef(A) from other countries. Of the 173 macrolide-resistant (erythromycin MIC >
      or =0.5 microg/mL) strains, 104 (60.1%) had erm(B), 47 (27.2%) had mef(A), and 22
      (12.7%) had erm(B) + mef(A). Strains expressing erm(B) or both erm(B) and mef(A)
      had high macrolide MIC(90)s (>64 microg/mL), except telithromycin (MIC(90), 0.25
      microg/mL). Of the 22 erm(B) + mef(A) strains, 10 had 4 distinct PFGE patterns
      and were mainly serotype 6B clones, which differed from those described in
      previous reports; 5 other strains had unique profiles.

PMID- 18068326
TI  - Antimicrobial activity of tigecycline against community-acquired methicillin
      resistant Staphylococcus aureus isolates recovered from North American medical
      centers.
AB  - A total of 1989 community-acquired methicillin-resistant Staphylococcus aureus
      (CA-MRSA) were susceptibility tested by broth microdilution. Pulsed-field gel
      electrophoresis, SCCmec type, and polymerase chain reaction for Panton-Valentine
      leukocidin (PVL) genes were also performed. The overall tigecycline
      susceptibility rate was 98.2%. Glycopeptides, quinupristin/dalfopristin,
      linezolid, and chloramphenicol were also active against this collection (< or
      =0.7% resistant). The vast majority (70.8%) of the CA-MRSA was SCCmec type IV,
      from which 88.4% belonged to the USA300-0114 clone and 94.7% were PVL positive.
      Tigecycline showed in vitro activity comparable with other highly active
      parenteral agents and represents an option for treating complicated infections
      caused by CA-MRSA.

PMID- 18068327
TI  - Non-polymerase-cycling-assembly-based chemical gene synthesis: strategies,
      methods, and progress.
AB  - Chemical gene synthesis is a powerful tool for basic biological research and
      biotechnology applications. During the last 30 years, major advances have been
      made in the chemical synthesis of DNA sequences ranging from fragments of <1 kb
      to multi-gene sequences of >30 kb. There is a need for simple, reproducible, less
      error-prone and cost-effective methods that guarantee successful synthesis of the
      desired genes and are amenable to automation. Many polymerase chain reaction
      (PCR)-based and non-polymerase-cycling-assembly (PCA)-based strategies have been
      developed for chemical gene synthesis. The PCR-based method has been the subject
      of several recent reviews. Here, we provide an overview of the progress in non
      PCA-based chemical gene synthesis using different strategies and methods,
      including enzymatic gene synthesis, annealing and ligation reaction, simultaneous
      synthesis of two genes via a hybrid gene, shotgun ligation and co-ligation,
      insertion gene synthesis, gene synthesis via one strand of DNA, template-directed
      ligation, ligase chain reaction, microarray-mediated gene synthesis, Blue Heron
      solid support technology and Sloning building block technology. The fundamental
      principle underlying each strategy, an example where applicable, and the
      advantages and disadvantages are discussed. The emphasis is on discussion of the
      most recent technologies and their potential applications, particularly for
      microarray-based genomics research.

PMID- 18068328
TI  - New section headings in the Table of Contents in Patient Education and
      Counseling.

PMID- 18068329
TI  - Carcinoid syndrome.
AB  - As clinical awareness increases, carcinoid is becoming increasingly identified,
      often at an earlier stage in the course of the disease. However, many patients
      remain undiagnosed until well into the late stages of the illness, at the time
      when their carcinoid syndrome becomes apparent. This review examines contemporary
      methods of detecting and assessing advanced carcinoid disease, and then continues
      to discuss strategies (both potentially curative and palliative) to control
      symptoms, and both prolong and improve quality of life for these patients.

PMID- 18068330
TI  - [Eruptive pseudoangiomatosis epidemic in a geriatric setting].

PMID- 18068331
TI  - Social temperament and lymph node innervation.
AB  - Socially inhibited individuals show increased vulnerability to viral infections,
      and this has been linked to increased activity of the sympathetic nervous system
      (SNS). To determine whether structural alterations in SNS innervation of lymphoid
      tissue might contribute to these effects, we assayed the density of
      catecholaminergic nerve fibers in 13 lymph nodes from seven healthy adult rhesus
      macaques that showed stable individual differences in propensity to socially
      affiliate (Sociability). Tissues from Low Sociable animals showed a 2.8-fold
      greater density of catecholaminergic innervation relative to tissues from High
      Sociable animals, and this was associated with a 2.3-fold greater expression of
      nerve growth factor (NGF) mRNA, suggesting a molecular mechanism for observed
      differences. Low Sociable animals also showed alterations in lymph node
      expression of the immunoregulatory cytokine genes IFNG and IL4, and lower
      secondary IgG responses to tetanus vaccination. These findings are consistent
      with the hypothesis that structural differences in lymphoid tissue innervation
      might potentially contribute to relationships between social temperament and
      immunobiology.

PMID- 18068333
TI  - Fractal dimension analysis of MR images reveals grey matter structure
      irregularities in schizophrenia.
AB  - The fractal dimension (FD) was used to reveal brain structure irregularities in
      patients with schizophrenia. FD provides a unique way of quantifying the shape
      complexity of cortical folding of the human brain. MR images were obtained from
      seven patients with schizophrenia that were compared with six healthy control
      subjects. The MR images were first segmented, and the FD was calculated for the
      grey/white matter boundary for the whole brain and the hemispheres separately,
      using the box-counting and Minkowski-Bouligand methods. The results showed that
      the patients had larger FD values than the controls, for the whole brain volume
      and right hemisphere.

PMID- 18068332
TI  - Parent psychological states predict changes in inflammatory markers in children
      with asthma and healthy children.
AB  - Previous research has shown that parent mental health is associated with asthma
      morbidity in children. However, the biological pathways explaining these
      relationships are not known. The present study tested whether parent
      psychological characteristics could predict longitudinal changes in inflammatory
      markers in children with asthma and a comparison group of healthy children. For
      this, 33 healthy children (17 m/16 f; 13.5 years) and 50 children with asthma (37
      m/13 f; 13.3 years) were assessed at two time points on average 208 days apart.
      Parent depression (CES-D) and perceived stress (PSS) were assessed at baseline,
      child depression (CDI) and anxiety (RCMAS) at follow-up. Asthma-relevant
      inflammatory markers eosinophil cationic protein (ECP) and stimulated interleukin
      4 (IL-4) production were measured at baseline and at follow-up. Hierarchical
      regression analyses controlling for asthma severity and medication use revealed
      that higher levels of parental perceived stress at baseline were associated with
      greater increases over time in children's IL-4 production (beta=.29, p=.019) as
      well as ECP release (beta=.27, p=.004). Additionally, higher levels of parental
      depression at baseline were associated with increases in ECP over time (beta=.19,
      p=.046). There was no evidence that these associations were mediated by child
      depression or anxiety. These results demonstrate that parental stress and
      depression at baseline predict increases in children's inflammatory profiles over
      a six month period. This pattern appeared in both children with asthma and
      healthy children, and was not due to effects on child psychological states. These
      changes in inflammatory makers may represent one biological mechanism underlying
      the association between parental distress and child asthma morbidity.

PMID- 18068334
TI  - Taxol-induced mitochondrial stress in melanoma cells is mediated by activation of
      c-Jun N-terminal kinase (JNK) and p38 pathways via uncoupling protein 2.
AB  - Taxol (paclitaxel) is a new antineoplastic drug that has shown promise in the
      treatment of different tumor types. However, the molecular mechanisms governing
      taxol-induced apoptosis are poorly understood. Activation of mitogen-activated
      protein (MAP) kinases is induced by a wide variety of external stress signals and
      may lead to apoptosis. Therefore, we challenged the human melanoma cell lines
      A375 and BLM with taxol and characterized the molecular mechanisms regulating
      taxol-induced apoptosis. Taxol resulted in the activation of apoptosis signal
      regulated kinase (ASK)1, c-jun NH(2)-terminal kinase (JNK), p38(MAPK) and
      extracellular-regulated kinase (ERK) together with the downregulation of
      uncoupling protein 2 (UCP2). In addition, reactive oxygen species (ROS) were
      induced and DNA-binding activity of the transcription factors AP-1, ATF-2 and ELK
      1 was enhanced. Ultimately, cytochrome c was released, and caspases-9 and -3 as
      well as PARP were cleaved. Pretreatment of melanoma cells with the JNK inhibitor
      (SP600125) or the p38 inhibitor (SB203580) blocked taxol-induced UCP2
      downregulation, ROS generation and apoptosis, whereas the ERK inhibitor (PD98059)
      had no such effect. Our data provide evidence that taxol-induced mitochondrial
      stress occurs through the activation of both JNK and p38 pathways, and suggest a
      novel role for UCP2 in the modulation of taxol-induced apoptosis of melanoma
      cells.

PMID- 18068335
TI  - SERCA2b and 3 play a regulatory role in store-operated calcium entry in human
      platelets.
AB  - Two agonist-releasable Ca(2+)stores have been identified in human platelets
      differentiated by the distinct sensitivity of their SERCA isoforms to
      thapsigargin (TG) and 2,5-di-(tert-butyl)-1,4-hydroquinone (TBHQ). Here we have
      examined whether the SERCA isotypes might be involved in store-operated
      Ca(2+)entry (SOCE) activated by the physiological agonist thrombin in human
      platelets. Ca(2+)-influx evoked by thrombin (0.01 U/mL) reached a maximum after 3
      min, which was consistent with the decrease in the Ca(2+)content in the stores;
      afterwards, the extent of SOCE decreased with no correlation with the
      accumulation of Ca(2+)in the stores. Inhibition of SERCA2b, by 10 nM TG, and
      SERCA3, with 20 microM TBHQ, individually or simultaneously, accelerated Ca(2+)
      store discharge and subsequently enhanced the extent of SOCE stimulated by
      thrombin. In addition, TG and TBHQ modified the time course of thrombin-evoked
      SOCE from a transient to a sustained increase in Ca(2+) influx, which reveals a
      negative role for SERCAs in the regulation of SOCE. This effect was consistent
      under conditions that inhibit Ca(2+) extrusion by PMCA or the Na(+)/Ca(2+)
      exchanger. Coimmunoprecipitation experiments revealed that thrombin stimulates
      direct interaction between SERCA2b and 3 with the hTRPC1 channel, an effect that
      was found to be independent of SERCA activity. In summary, our results suggest
      that SERCA2b and 3 modulate thrombin-stimulated SOCE probably by direct
      interaction with the hTRPC1 channel in human platelets.

PMID- 18068336
TI  - Raptor-rictor axis in TGFbeta-induced protein synthesis.
AB  - Transforming growth factor-beta (TGFbeta) stimulates pathological renal cell
      hypertrophy for which increased protein synthesis is critical. The mechanism of
      TGFbeta-induced protein synthesis is not known, but PI 3 kinase-dependent Akt
      kinase activity is necessary. We investigated the contribution of downstream
      effectors of Akt in TGFbeta-stimulated protein synthesis. TGFbeta increased
      inactivating phosphorylation of Akt substrate tuberin in a PI 3 kinase/Akt
      dependent manner, resulting in activation of mTOR kinase. mTOR activity increased
      phosphorylation of S6 kinase and the translation repressor 4EBP-1, which were
      sensitive to inhibition of both PI 3 kinase and Akt. mTOR inhibitor rapamycin and
      a dominant negative mutant of mTOR suppressed TGFbeta-induced phosphorylation of
      S6 kinase and 4EBP-1. PI 3 kinase/Akt and mTOR regulated dissociation of 4EBP-1
      from eIF4E to make the latter available for binding to eIF4G. mTOR and 4EBP-1
      modulated TGFbeta-induced protein synthesis. mTOR is present in two multi protein
      complexes, mTORC1 and mTORC2. Raptor and rictor are part of mTORC1 and mTORC2,
      respectively. shRNA-mediated downregulation of raptor inhibited TGFbeta
      stimulated mTOR kinase activity, resulting in inhibition of phosphorylation of S6
      kinase and 4EBP-1. Raptor shRNA also prevented protein synthesis in response to
      TGFbeta. Downregulation of rictor inhibited serine 473 phosphorylation of Akt
      without any effect on phosphorylation of its substrate, tuberin. Furthermore,
      rictor shRNA increased phosphorylation of S6 kinase and 4EBP-1 in TGFbeta
      independent manner, resulting in increased protein synthesis. Thus mTORC1
      function is essential for TGFbeta-induced protein synthesis. Our data also
      provide novel evidence that rictor negatively regulates TORC1 activity to control
      basal protein synthesis, thus conferring tight control on cellular hypertrophy.

PMID- 18068337
TI  - A novel PTCH1 mutation in a patient of nevoid basal cell carcinoma syndrome.

PMID- 18068338
TI  - The effect of filamentous bacteria on foam production and stability.
AB  - Bacteria have been implicated in the formation of viscous brown foams that can
      appear suddenly on wastewater treatment plants. Three strains of the filamentous
      bacterium Gordonia amarae, isolated from wastewater treatment plants, were
      investigated to determine their effect on foam formation and stabilisation.
      During the exponential phase of the bacterial growth a biosurfactant was formed,
      causing a significant drop in the surface tension of the filtered medium and the
      formation of persistent foam. Foaming tests in the presence and absence of
      bacteria showed that bacteria increased foam persistence, most probably by
      reducing the drainage from the lamellae between bubbles. Experiments showed that
      > or =55% of the three bacterial strains partitioned into the foam produced by
      the biosurfactant, indicating that their surfaces were hydrophobic. The extent of
      partitioning was independent of the growth stage, suggesting that the cell
      surface hydrophobicity did not change with age, or with cell viability. This work
      shows that, although the G. amarae cells themselves do not cause foaming, they do
      produce biosurfactant, which aids foam formation, and they stabilise the foam by
      reducing the rate of drainage from the foam lamellae.

PMID- 18068339
TI  - Antioxidant potential and indole alkaloid profile variations with water deficits
      along different parts of two varieties of Catharanthus roseus.
AB  - The variations in antioxidant potentials and indole alkaloid content were studied
      in the present investigation, in two varieties (rosea and alba) of Catharanthus
      roseus, an important herb used in traditional as well as modern medicine, exposed
      to water deficit stress. The antioxidant and alkaloid profiles were estimated
      from root, stem, leaf, flowers and pods. The antioxidant potentials were examined
      in terms of non-enzymatic antioxidant molecules and activities of antioxidant
      enzymes. The non-enzymatic antioxidant molecules studied were ascorbic acid (AA),
      alpha-tocopherol (alpha-toc) and reduced glutathione (GSH). The estimated
      antioxidant enzymes were superoxide dismutase (SOD), ascorbate peroxidase (APX),
      catalase (CAT), peroxidase (POX) and polyphenol oxidase (PPO). The antioxidant
      concentrations and activities of antioxidant enzymes were high under water
      deficit stress in all parts of the plants. Indole alkaloid content was high in
      the roots of rosea variety in response to stress when compared to alba variety.

PMID- 18068340
TI  - Impact of PAMAM G2 and G6 dendrimers on bovine serum albumin (fatty acids free
      and loaded with different fatty acids).
AB  - Dendrimers are a new class of nanotechnological polymers suitable for drug
      targeting, microarray systems or detoxication. The present study is devoted to a
      detailed analysis of binding between PAMAM dendrimers and bovine serum albumin
      (fatty acid free or loaded with oleic, linoleic, oleic+linoleic or
      oleic+linoleic+arachodonic acids) by measuring zeta-potential, fluorescence
      quenching, fluorescence anisotropy and electron paramagnetic resonance. Addition
      of PAMAM G2 and G6 dendrimers to protein solutions resulted in attachment to the
      protein molecule. The PAMAM dendrimers also competed with BSA for fatty acids if
      two or three fatty acids were loaded per protein. This can lead to the extraction
      of fatty acids from BSA to the PAMAM dendrimer.

PMID- 18068341
TI  - Plasma palmitoleic acid, a product of stearoyl-coA desaturase activity, is an
      independent marker of triglyceridemia and abdominal adiposity.
AB  - BACKGROUND AND AIM: In an animal model VLDL-triglyceride secretion is highly
      dependent on stearoyl-coA desaturase (SCD) activity and could explain abdominal
      fattening. The aim was to assess the relationship of plasma palmitoleic acid
      content, a product of SCD activity, with triglyceridemia and abdominal adiposity
      in humans. METHODS: We evaluated 134 healthy men. Plasma palmitoleic acid content
      was used as an indirect measurement of SCD activity because that enzyme catalyzes
      the desaturation from saturated to monounsaturated fatty acids and palmitoleic
      acid intake is very small. RESULTS: Subjects with triglycerides > or =75th
      percentile had a higher palmitoleic acid content than those with triglycerides
      <75th percentile (3.8+/-0.8 vs 2.8+/-0.9%, p<0.0001). Triglyceridemia was
      strongly correlated with palmitoleic acid content (PAC) (r=0.533, p<0.001). Mean
      triglyceridemia was 114% higher (1.43+/-0.75 vs 0.67+/-0.22 mmol/l) in the fourth
      quartile than in the first quartile of palmitoleic acid content. In a stepwise
      logistic regression analysis, palmitoleic acid content was the most strongly and
      independently associated parameter with triglyceridemia, and also with waist
      circumference when triglyceridemia was not included in the analysis. CONCLUSION:
      Plasma palmitoleic acid content, a product of SCD activity, is an independent
      marker of triglyceridemia and abdominal adiposity in men. This enzyme (SCD) could
      represent a target for prevention and treatment of these metabolic disorders in
      particular in subjects at risk of developing a metabolic syndrome.

PMID- 18068342
TI  - Selection of drug candidates for gastroretentive dosage forms: pharmacokinetics
      following continuous intragastric mode of administration in a rat model.
AB  - The purpose of the study was to evaluate the pharmacokinetic effects obtained by
      gastroretentive dosage form (GRDF) for drugs absorbed by passive paracellular
      diffusion (atenolol, acyclovir) or active transport (valacyclovir). Model drugs
      were delivered as gastric infusion (GInf) through an implanted catheter
      (resembling GRDF), intravenous, oral (PO), and colonic administration to rats.
      For atenolol (highly soluble drug), GInf resulted in a prolonged Tmax and reduced
      Cmax in comparison to PO, whereas bioavailability was similar. Bioavailability
      after colonic bolus was significantly lower. Results were also simulated by a
      pharmacokinetic model. For acyclovir, GInf and PO demonstrated almost the same
      pharmacokinetic profile with low bioavailability, most probably due to the
      solubility-limited absorption. Valacyclovir demonstrated the significant change
      in the shape of pharmacokinetic profile as a function of the rate of gastric
      delivery, without variation in bioavailability. Valacyclovir was not absorbed
      from colon. Experimental and theoretical methodologies to assess the
      pharmacokinetic influences of GRDF mode of administration were developed,
      avoiding the need to compound the drug in a dosage form. GRDF provides a mean for
      controlled release of compounds that are absorbed by active transport in the
      upper intestine. It also enables controlled delivery for paracellularly absorbed
      drugs without a decrease in bioavailability.

PMID- 18068343
TI  - Starring stellate cells in liver immunology.
AB  - Stellate cells are star-shaped cells located in the liver and mediate a multitude
      of primarily non-immunological functions. They play a pivotal role in the
      metabolism of vitamin A and store 80% of total body retinol. Upon activation,
      stellate cells differentiate to myofibroblasts for production of extracellular
      matrix, leading to liver fibrosis. Moreover, activated stellate cells regulate
      liver blood flow through vasoconstriction implicated in portal hypertension.
      Earlier work demonstrated stellate cell derived secretion of chemokines and
      cytokines such as transforming growth factor beta (TGF-beta), suggesting an
      association with immunological processes. Indeed, recent evidence indicated that
      hepatic stellate cells perform potent APC function for stimulation of NKT cells
      as well as CD8 and CD4 T cells. Additionally, stellate cell mediated antigen
      presentation induced protective immunity against bacterial infection. Current
      experiments reveal that the presenting ability of stellate cells is the key to
      antigen-dependent T cell instruction by vitamin A derived retinoic acid. Finally,
      future studies will show whether in the firmament of immunology stellate cells
      will represent fixed or falling stars.

PMID- 18068344
TI  - Factors related to quality of life in patients receiving home mechanical
      ventilation.
AB  - OBJECTIVES: The objective of this study was to evaluate factors associated with
      health-related quality of life (HRQOL) among patients receiving home mechanical
      ventilation (HMV). METHODS: Observational, cross-sectional study. Patients
      receiving HMV were recruited from hospital outpatients facilities at five
      participating centers; a single follow-up visit was scheduled. The Spanish
      version of the Severe Respiratory Insufficiency (SRI) Questionnaire was used and
      the following variables were collected: socio-demographic status, previous
      medical history (Charlson-Age Comorbidity Index), current symptoms,
      administration of questionnaires, pulmonary function tests (PFT), current
      ventilatory support, and oxygen therapy. RESULTS: One hundred and fifteen
      patients (57 males and 58 females, mean age 62+/-13 years) were investigated. The
      reasons for HMV were as follows: thoracic cage abnormalities (33 patients),
      obesity hypoventilation syndrome (37 patients), neuromuscular disorders (18
      patients), sequelae of tuberculosis (12 patients), and chronic obstructive
      pulmonary disease (15 patients). In a bivariate approach, dyspnea, the number of
      hospitalizations, and the number of emergency room admissions in last year were
      the main predictors of each HRQOL dimension. Multivariate analysis showed that
      dyspnea, FEV(1)/FVC, and the number of hospitalizations in the previous year were
      independently associated with HRQOL. CONCLUSIONS: HRQOL of patients receiving HMV
      is influenced by many factors, especially by dyspnea and the number of
      admissions. An obstructive pattern in the PFT also influences HRQOL. These
      findings may have therapeutic implications.

PMID- 18068345
TI  - Effect of alkaline pretreatment on anaerobic digestion of solid wastes.
AB  - The introduction of the anaerobic digestion for the treatment of the organic
      fraction of municipal solid waste (OFMSW) is currently of special interest. The
      main difficulty in the treatment of this waste fraction is its biotransformation,
      due to the complexity of organic material. Therefore, the first step must be its
      physical, chemical and biological pretreatment for breaking complex molecules
      into simple monomers, to increase solubilization of organic material and improve
      the efficiency of the anaerobic treatment in the second step. This paper
      describes chemical pretreatment based on lime addition (Ca(OH)2), in order to
      enhance chemical oxygen demand (COD) solubilization, followed by anaerobic
      digestion of the OFMSW. Laboratory-scale experiments were carried out in
      completely mixed reactors, 1 L capacity. Optimal conditions for COD
      solubilization in the first step of pretreatment were 62.0 mEq Ca(OH)2/L for 6.0
      h. Under these conditions, 11.5% of the COD was solubilized. The anaerobic
      digestion efficiency of the OFMSW, with and without pretreatment, was evaluated.
      The highest methane yield under anaerobic digestion of the pretreated waste was
      0.15 m3CH4/kg volatile solids (VS), 172.0% of the control. Under that condition
      the soluble COD and VS removal were 93.0% and 94.0%, respectively. The results
      have shown that chemical pretreatment with lime, followed by anaerobic digestion,
      provides the best results for stabilizing the OFMSW.

PMID- 18068346
TI  - Label-free electrochemical detection of DNA using ferrocene-containing cationic
      polythiophene and PNA probes on nanogold modified electrodes.
AB  - A label-free electrochemical method for the detection of DNA-PNA hybridization
      using a water-soluble, ferrocene-functionalized polythiophene transducer and
      single-stranded PNA probes on the nanogold modified electrode is investigated.
      Nanogold modified electrodes can largely increase the immobilization amount of ss
      PNA capture probe and lead to an increase of the electrical signal. The ferrocene
      containing cationic polythiophene do not interact electrostatically with the PNA
      probes due to the absence of the anionic phosphate groups on the PNA probes. But
      after DNA-PNA hybridization, cationic polythiophene is adsorbed on the DNA
      backbone, giving a clear hybridization detection signal in differential pulse
      voltammetry (DPV). Very good discrimination against non-complementary DNA and
      four-base mismatch DNA is observed. These studies show that the proposed method
      can provide an alternative for expanding the range of detection methods available
      for DNA hybridization.

PMID- 18068347
TI  - Enhanced resonance light scattering based on biocatalytic growth of gold
      nanoparticles for biosensors design.
AB  - The biocatalytic growth of gold nanoparticles (Au-NPs) has been employed in the
      design of new optical biosensors based on the enhanced resonance light scattering
      (RLS) signals. Both absorption spectroscopy and transmission electron microscopy
      (TEM) analysis revealed Au-NP seeds could be effectively enlarged upon the
      reaction with H(2)O(2), an important metabolite that could be generated by many
      biocatalytic reactions. Upon the stepwise enlargement of Au-NPs, the light
      scattering intensity could be greatly enhanced, which then allowed the
      quantitative detection of the analyte, H(2)O(2). Further combination of the
      biocatalytic reaction that can yield H(2)O(2) by using the enzyme, glucose
      oxidase, with the enlargement of Au-NPs enabled the design of a sensitive glucose
      biosensor using the RLS technique. In the present study, we could achieve the
      detection of glucose in a linear range of 1.0 x 10(-6) M to 1.1 x 10(-4) M, with
      detection limit of 6.8 x 10(-7) M.

PMID- 18068348
TI  - The role of mu opioid receptor desensitization and endocytosis in morphine
      tolerance and dependence.
AB  - Following activation, most G protein coupled receptors undergo regulation by a
      cascade of events that promote receptor desensitization and endocytosis.
      Following endocytosis, receptors can then be recycled to the plasma membrane,
      retained in an intracellular compartment, or targeted for degradation. For
      receptors that are recycled, like the mu opioid receptor (MOR), endocytosis
      serves as the first step toward resensitizing receptors. For receptors that are
      degraded, endocytosis serves as the first step toward receptor downregulation.
      Thus, for receptors like the MOR, the desensitization-endocytosis-resensitization
      cycle serves as a rapid and dynamic means to titrate signaling through the
      receptor. However, not all agonist ligands at the MOR promote the same degree of
      receptor desensitization and endocytosis. For example, the endogenous peptide
      ligands at the MOR induce rapid desensitization, endocytosis, and recycling. By
      contrast, morphine induces only weak or partial desensitization and little to no
      endocytosis. As a consequence, signal transduction promoted by morphine is less
      dynamic than that induced by endogenous ligands as well as other opioid agonists
      that promote endocytosis. The resulting imbalance of desensitization-endocytosis
      resensitization has at least two consequences: (1) in cell types where morphine
      induces desensitization but not endocytosis and/or resensitization,
      desensitization is protracted; (2) in cell types where morphine induces neither
      desensitization nor endocytosis, prolonged signaling through the receptor leads
      to multiple cellular adaptations downstream of receptor-G protein coupling. Both
      protracted desensitization and adaptive cellular changes probably contribute to
      the pronounced in vivo tolerance and dependence that occur with chronic morphine
      treatment. As a consequence, facilitating receptor endocytosis, using either
      genetic or pharmacological approaches, can restore the balance of signaling
      through the receptor and affect the development of tolerance and dependence.

PMID- 18068349
TI  - Combination of O6-methylguanine-DNA methyltransferase and thymidylate synthase
      for the prediction of fluoropyrimidine efficacy.
AB  - We investigated the correlation between the response to fluoropyrimidines as
      first-line therapy and the expressions of genes in patients with primary
      colorectal cancer (CRC). The study group comprised 92 patients with metastatic
      CRC. Total RNA was isolated from laser-captured tumour cells in surgically
      resected primary lesions, and gene expression was quantitatively evaluated by
      real-time RT-PCR assay. Low thymidylate synthase (TS), low gamma-glutamyl
      hydrolase, high reduced folate carrier 1, high O6-methylguanine-DNA
      methyltransferase (MGMT) and low cyclin E expressions were associated with a good
      response (P=0.0030, 0.0250, 0.0120, 0.0030 and 0.0020, respectively) on
      univariate analysis. On multivariate logistic regression analysis, TS and MGMT
      remained independent predictors of the response. The clinical response rates were
      63.2% in the low TS or high MGMT group and 14.3% in high TS and low MGMT group
      (P<0.0001). The combination of high TS and low MGMT expression is a significant
      predictor of a poor response to fluoropyrimidine treatment.

PMID- 18068351
TI  - Thymic epithelial tumours: a population-based study of the incidence, diagnostic
      procedures and therapy.
AB  - The population-based incidence, diagnostic procedures, therapy and survival of
      thymic epithelial tumours were determined using the Netherlands National
      Pathological Archives and the Netherlands Cancer Registry. Excess mortality
      compared to the Netherlands standard population was estimated by relative
      survival analysis. Between 1994 and 2003, 537 thymic epithelial tumours were
      diagnosed. The incidence of all thymic epithelial tumours was 3.2/1,000,000.
      Diagnosis was obtained by primary resection in 56% of cases. Survival data were
      available for 232 cases. Not only thymic carcinomas (type C) but also thymomas
      (types B1-B3) were associated with excess mortality. Cases that underwent
      resection (78%) had a better survival than non-operated cases (median survival
      >10 years versus 1.1 years, p<0.001). Amongst the surgically treated cases
      (n=180), the completeness of resection did not predict survival (p=0.53). Thymic
      epithelial tumours are rare. Excess mortality was observed in the majority of
      tumours. Surgery offers the best perspectives, even if the resection is
      incomplete.

PMID- 18068352
TI  - Wood-plastic composites as promising green-composites for automotive industries!
AB  - Wood-plastic composite (WPC) is a very promising and sustainable green material
      to achieve durability without using toxic chemicals. The term WPCs refers to any
      composites that contain plant fiber and thermosets or thermoplastics. In
      comparison to other fibrous materials, plant fibers are in general suitable to
      reinforce plastics due to relative high strength and stiffness, low cost, low
      density, low CO2 emission, biodegradability and annually renewable. Plant fibers
      as fillers and reinforcements for polymers are currently the fastest-growing type
      of polymer additives. Since automakers are aiming to make every part either
      recyclable or biodegradable, there still seems to be some scope for green
      composites based on biodegradable polymers and plant fibers. From a technical
      point of view, these bio-based composites will enhance mechanical strength and
      acoustic performance, reduce material weight and fuel consumption, lower
      production cost, improve passenger safety and shatterproof performance under
      extreme temperature changes, and improve biodegradability for the auto interior
      parts.

PMID- 18068353
TI  - Production of hydrogen and methane from potatoes by two-phase anaerobic
      fermentation.
AB  - A two-phase anaerobic process to produce hydrogen and methane from potatoes was
      investigated. In the first phase, hydrogen was produced using heat-shocked
      sludge. About 12h lag-phase vanished, hydrogen yield increased from 200.4 ml/g
      TVS to 217.5 ml/g-TVS and the maximum specific hydrogen production rate also
      increased from 703.4 ml/g-VSS d to 800.5 ml/g-VSS d when improved substrate was
      used, in which Cl(-) was substituted for SO(4)(2-). Better performances of 271.2
      ml-H(2)/g-TVS and 944.7 ml-H(2)/g-VSS d were achieved when potatoes were
      pretreated by alpha amylase and glucoamylase. In the second phase, methane was
      produced from the residual of the first phase using methanogens. The maximum
      additional methane yield was 157.9 ml/g-TVS and the maximum specific methane
      production rate was 102.7 ml/g-VSS d. The results showed that the energy
      efficiency increased from about 20% (hydrogen production process) to about 60%,
      which indicated the energy efficiency can be improved by combined hydrogen and
      methane production process.

PMID- 18068350
TI  - Tamoxifen: catalyst for the change to targeted therapy.
AB  - In the early 1970s, a failed post-coital contraceptive, ICI 46,474, was
      reinvented as tamoxifen, the first targeted therapy for breast cancer. A cluster
      of papers published in the European Journal of Cancer described the idea of
      targeting tamoxifen to patients with oestrogen receptor positive tumours, and
      proposed the strategic value of using long-term tamoxifen therapy in an adjuvant
      setting with a consideration of the antitumour properties of the hydroxylated
      metabolites of tamoxifen. At the time, these laboratory results were slow to be
      embraced by the clinical community. Today, it is estimated that hundreds of
      thousands of breast cancer patients are alive today because of targeted long-term
      adjuvant tamoxifen therapy. Additionally, the first laboratory studies for the
      use of tamoxifen as a chemopreventive were published. Eventually, the worth of
      tamoxifen was tested as a chemopreventive and the drug is now known to have an
      excellent risk benefit ratio in high risk pre-menopausal women. Overall, the
      rigorous investigation of the pharmacology of tamoxifen facilitated tamoxifen's
      ubiquitous use for the targeted treatment of breast cancer, chemoprevention and
      pioneered the exploration of selective oestrogen receptor modulators (SERMs).
      This new concept subsequently heralded the development of raloxifene, a failed
      breast cancer drug, for the prevention of osteoporosis and breast cancer without
      the troublesome side-effect of endometrial cancer noted in post-menopausal women
      who take tamoxifen. Currently, the pharmaceutical industry is exploiting the SERM
      concept for all members of the nuclear receptor superfamily so that medicines can
      now be developed for diseases once thought impossible.

PMID- 18068354
TI  - Supercritical carbon dioxide extraction of astaxanthin from Haematococcus
      pluvialis with vegetable oils as co-solvent.
AB  - Soybean oil and olive oil were investigated as continuous co-solvents for
      supercritical carbon dioxide (SC-CO(2)) extraction of astaxanthin from
      Haematococcus pluvialis. Without co-solvents, only 25.40+/-0.79% efficiency was
      achieved with SC-CO(2) extraction at 70 degrees C and 40 MPa at a continuous flow
      rate of 3 mL min(-1) for 5h. In the presence of soybean oil or olive oil as a co
      solvent, the extraction efficiency was enhanced, with the most appropriate level
      of soybean oil in the solvent mixture being 10% by volume. At this concentration
      and the above extraction conditions, the highest extraction efficiency of 36.36+/
      0.79% was obtained for soybean oil, a 30% increase in extraction efficiency
      compared with SC-CO(2) extraction without soybean oil, whereas the 10% olive oil
      increased the extraction efficiency further to 51.03+/-1.08%, which was
      comparable to that obtained using ethanol as co-solvent.

PMID- 18068355
TI  - Effect of sulfide to nitrate ratios on the simultaneous anaerobic sulfide and
      nitrate removal.
AB  - Present investigation deals with the effect of sulfide to nitrate (S/N) molar
      ratio on the simultaneous anaerobic sulfide and nitrate removal on capacity,
      stability and selectivity of the process. The volumetric sulfide-sulfur and
      nitrate-nitrogen removal rates at molar S/N ratio of 5:2 were 4.86 kg(m(3)d)(-1)
      and 0.99 kg(m(3)d)(-1), respectively, which were higher than those at S/N molar
      ratios of 5:5 and 5:8. Moreover, the fluctuations in the effluent at S/N ratio of
      5:2 were less than those at the other two tested ratios. During the operation,
      the ratio of converted sulfide to converted nitrate tended to approach 5:2. The
      selectivity for elemental sulfur and dinitrogen was improved when the S/N molar
      ratio was set at 5:2 rather than 5:5 or 5:8. The process became unstable if the
      influent sulfide surpassed its critical concentration. The electron balance
      between reactants was also analyzed for different S/N molar ratios.

PMID- 18068356
TI  - Removal of lead (Pb(2+)) by the cyanobacterium Gloeocapsa sp.
AB  - Pb(2+) removal ability of the viable-freshwater cyanobacterium Gloeocapsa sp. was
      studied in batch experiments. Gloeocapsa sp. was cultured in the Medium 18 with
      pH adjusted to 3, 4, 5, 6 and 7. Growth was subsequently determined based on the
      increase of chlorophyll-a content. Gloeocapsa sp. was able to grow at all pH
      levels tested, except at pH 3. Removal of Pb(2+) was then further studied under
      pH 4. The results showed that Pb(2+) concentration in the range of 0-20 mg L(-1)
      was not inhibitory to Gloeocapsa sp. growth but reduced its Pb(2+) removal
      efficiency (by 4.5% when Pb(2+) concentration increased from 2.5 to 20 mg L(-1)).
      Pb(2+) removal characteristics followed the Langmuir adsorption isotherm with the
      maximum removal capacity (q(max)) of 232.56 mg g(-1). Adsorption of Pb(2+) by
      this cyanobacterium followed the second order rate reaction and intraparticle
      diffusion was likely the rate-determining step. The initial rate of
      Pb(2+)adsorption during intraparticle diffusion was slower under light than under
      dark conditions, indicating that light probably slowed down the initial rate of
      intraparticle diffusion through the repulsion effects on cell membrane.

PMID- 18068357
TI  - Integration of a Coagulation/Flocculation step in a biological sequencing batch
      reactor for COD and nitrogen removal of supernatant of anaerobically digested
      piggery wastewater.
AB  - The supernatant from mesophilic anaerobic digestion of piggery wastewater is
      characterised by a high amount of COD (4.1 g COD L(-1)), ammonium (2.3g NH(4)(+)
      NL(-1)) and suspended solids (2.5 g SS L(-1)). This effluent can be efficiently
      treated by means of a Sequencing Batch Reactor (SBR) strategy for biological COD,
      SS and nitrogen removal including a Coagulation/Flocculation step. Total COD and
      SS reduction yields higher than 66% and 74%, respectively, and a total nitrogen
      removal (via nitrite) of more than 98% were reached when working with HRT 2.7
      days, SRT 12 days, temperature 32 degrees C, three aerobic/anoxic periods,
      without external control of pH and under limited aeration flow. The inhibition of
      nitrite oxidizing biomass was achieved by the working free ammonia concentration
      and the restricted air supply (dissolved oxygen concentration below 1 mg O(2)L(
      1)). Since a part of the total COD was colloidal and/or refractory, a
      Coagulation/Flocculation step was implemented inside the SBR operating strategy
      to meet a suitable effluent quality to be discharged. Several Jar-Tests
      demonstrated that the optimal concentration of FeCl(3) was 800 mg L(-1). A
      respirometric assay showed that this coagulant dosage did not affect the
      biological activity of nitrifying/denitrifying biomass.

PMID- 18068358
TI  - Decolorization of molasses wastewater by yeast strain, Issatchenkia orientalis
      No. SF9-246.
AB  - Among 2,402 strains of yeast isolated from various sources in Thailand, a strain
      No. SF9-246 identified as Issatchenkia orientalis, showed the highest potential
      for use in decolorization of molasses wastewater. In a malt extract-glucose
      peptone broth (MYGP) culture containing melanoidin pigment (MP) at 30 degrees C a
      60.2% decolorization was obtained within 7 days. The strain appeared to enhance
      both MP-degradation and MP-adsorption. The strain showed MP, chemical oxygen
      demand (COD) and biological oxygen demand (BOD(5)) removal efficiencies of 91.2%,
      80.0% and 77.4%, respectively from anaerobic-treated molasses wastewater solution
      (T-MWW), collected from an anaerobic pond. The wastewater contained 2.5% glucose,
      0.1% NH(4)Cl, and 0.1% KH(2)PO(4). The pH was adjusted to 5.0 at 30 degrees C for
      7 days batch type culture system. The strain showed almost constant
      decolorization yield of 75-80% over 7 days in a periodical feeding system of 10%
      fresh T-MWW with the culture system. The strain provided a constant
      decolorization yield about 70% during 3 replacement cycles. Gel filtration
      chromatography showed that larger molecular weight fraction of MP solution was
      rapidly removed, while the smaller molecular weight fraction remained in the
      effluent.

PMID- 18068359
TI  - Sustained expression of keratinase gene under PxylA and PamyL promoters in the
      recombinant Bacillus megaterium MS941.
AB  - The ker gene encoding pre-pro keratinase of Bacillus licheniformis MKU3 was
      cloned with xylose inducible promoter (PxylA) or alpha-amylase promoter (PamyL)
      or both in Escherichia coli-Bacillus shuttle vector, pWH1520 generating
      recombinant plasmids pWHK3, pWAK3 and pWXAK3 respectively. Compared with
      Bacillius megaterium MS941 (pWXAK3) expressing ker gene with PxylA-PamyL
      promoters, B. megaterium MS941 (pWAK3) with PamyL displayed higher keratinase
      yield (168.6 U/ml) and specific activity (14.59 U/mg) after 36 h of growth in LB
      medium, however the keratinase yield decreased in the culture grown in LB medium
      supplemented with starch or xylose or both. A maximum yield of 186.3 U/ml with
      specific activity of 17.25 U/mg was obtained from xylose induced keratinase
      expression in B. megaterium MS941 (pWHK3) grown for 24h. The recombinant plasmids
      were stably maintained with sustained expression of keratinase for about 60
      generations in B. megaterium MS941 rather than in B. megaterium 1,4945.

PMID- 18068360
TI  - Effect of static magnetic field on synthesis of polyhydroxyalkanoates from
      different short-chain fatty acids by activated sludge.
AB  - The effect of static magnetic field on the production of polyhydroxyalkanoates
      (PHAs) from different short-chain fatty acids by activated sludge process under
      aerobic dynamic feeding (ADF) technique was evaluated in four sequencing batch
      reactors (SBRs) with static magnetic field intensity of 42 mT (SBR1), 21 mT
      (SBR2), 7 mT (SBR3), 0 mT (SBR4), respectively. It was demonstrated that the
      static magnetic exposure had definitely influenced the biosynthesis of PHAs when
      acetate, butyrate and propionate were fed solely or each two mixture or three
      substrates mixture, and the effect was dependent on field strength: the maximum
      poly-3-hydroxybutyrate (PHB) production occurring at 7 mT, and the minimum one at
      42 mT; the maximum poly-3-hydroxyvalerate (PHV) production occurring at 21 mT,
      and the minimum one at 0 mT.

PMID- 18068361
TI  - Synthesis and SAR of novel 1,1-dialkyl-2(1H)-naphthalenones as potent HCV
      polymerase inhibitors.
AB  - A series of gem-dialkyl naphthalenone derivatives with varied alkyl substitutions
      were synthesized and evaluated according to their structure-activity
      relationship. This investigation led to the discovery of potent inhibitors of the
      hepatitis C virus at low nanomolar concentrations in both enzymatic and cell
      based HCV genotype 1a assays.

PMID- 18068363
TI  - Development of CXCR3 antagonists. Part 4: discovery of 2-amino-(4
      tropinyl)quinolines.
AB  - The synthesis and biological evaluation of a novel series of 2-aminoquinoline
      substituted piperidines and tropanes incorporating a homotropene moiety is herein
      described. The series exhibits potent antagonism of the CXCR3 receptor and
      superior physicochemical properties. Compound 24d was found to be orally
      bioavailable, and PK/PD studies suggested it as a suitable tool for studying the
      role of CXCR3 in models of disease.

PMID- 18068362
TI  - Possible chemical mechanisms underlying the antitumor activity of S
      deoxyleinamycin.
AB  - Though less potent than the parent natural product leinamycin, S-deoxyleinamycin
      displays activity against human cancer cell lines that is comparable to many
      clinically used agents. The results reported here suggest that the 1,2-dithiolan
      3-one heterocycle found in S-deoxyleinamycin reacts with thiols to generate a
      persulfide intermediate (RSS(-)) that could deliver biologically active
      polysulfides, hydrogen sulfide, and reactive oxygen species (O2*-, H(2)O(2), and
      HO*) to the interior of cells.

PMID- 18068364
TI  - Synthesis and antimycobacterial evaluation of new trans-cinnamic acid hydrazide
      derivatives.
AB  - In this work, we report the synthesis and the antimycobacterial evaluation of new
      trans-cinnamic acid derivatives of isonicotinic acid series (5) and benzoic acid
      series (6), designed by exploring the molecular hybridization approach between
      isoniazid (1) and trans-cinnamic acid derivative (3). The minimum inhibitory
      concentration (MIC) of the compounds 5a-d and 6c exhibited activity between 3.12
      and 12.5 microg/mL and could be a good start point to find new lead compounds
      against multi-drug resistant tuberculosis.

PMID- 18068365
TI  - Microwave-assisted synthesis and antimicrobial activities of flavonoid
      derivatives.
AB  - Eleven flavonoid derivatives were synthesised using a modified Baker-Venkataraman
      rearrangement, and subsequent microwave-assisted closure of the heterocyclic
      ring. All of the synthetic compounds displayed antifungal activity against
      Aspergillus niger and Fusarium oxysporium, and two of the synthetic flavonoid
      analogues exhibited significant activity against methicillin-resistant
      Staphylococcus aureus.

PMID- 18068366
TI  - Policing Tic 'n' Toc, the doorway to chloroplasts.
AB  - The organization of eukaryotic cells into different membrane-enclosed
      compartments requires an ordered and regulated system for targeting and
      translocating proteins synthesized in the cytosol across organellar membranes.
      Protein translocation through integral membrane proteinaceous complexes shares
      common principles in different organelles, whereas molecular mechanisms and
      energy requirements are diverse. Translocation into mitochondria and plastids
      requires most proteins to cross two membranes, and translocation must be
      regulated to accommodate environmental or metabolic changes. In the last decade,
      the first ideas were formulated about the regulation of protein translocation
      into chloroplasts, thereby laying the foundation for this field. Here, we
      describe recent models for the regulation of translocation by precursor protein
      phosphorylation, receptor dimerization, redox sensing and calcium signaling. We
      suggest how these mechanisms might fit within the regulatory framework for the
      entry of proteins into chloroplasts.

PMID- 18068367
TI  - Double life of centrioles: CP110 in the spotlight.
AB  - Centrioles lead an important double life: they can give rise to the centrosome or
      convert to basal bodies and template cilia. Little is known about the control of
      centriole fate. Spektor and colleagues have now identified a centriolar complex,
      composed of CP110 and CEP97, which inhibits centriole to basal body conversion,
      preventing cilia formation. This work paves the way to understanding centriole
      and cilia biogenesis, which are two processes misregulated in human diseases,
      such as cancer and polycystic kidney disease.

PMID- 18068368
TI  - Mitochondrial stress signaling: a pathway unfolds.
AB  - Disruption of protein homeostasis in mitochondria elicits a cellular response,
      which upregulates mitochondrial chaperones and other factors that serve to
      remodel the mitochondrial-folding environment. In a recent study, Haynes and
      colleagues uncovered a novel signal transduction pathway underlying this process.
      The upstream mitochondrial component of this pathway is an orthologue of
      Escherichia coli ClpP, which functions in the bacterial heat-shock response.
      These findings suggest that molecular aspects of stress sensing might be
      conserved between bacteria and mitochondria.

PMID- 18068369
TI  - Limbic leukotomy for intractable major affective disorders: a 7-year follow-up
      study using nine comprehensive psychiatric test evaluations.
AB  - Surgical treatment of psychiatric disease can be effective for some patients with
      severe, intractable disorders. However, few long-term studies using comprehensive
      psychiatric test evaluation of patients who have undergone surgery have been
      carried out. Stereotactic limbic leukotomy (subcaudate tractotomy and
      cingulotomy) was performed via radiofrequency thermocoagulation on 16 patients
      with intractable major affective disorders (bipolar). Patients were followed for
      7 years, and nine complete psychiatric test evaluations were conducted before and
      after the procedure. Clinical outcomes were evaluated using the Current Global
      Psychiatric-Social Status Scale (CGPSS). In the 7-year follow-up, mean scores on
      the Hamilton Depression Rating Scale and the Beck Depression Inventory declined
      significantly from 42+/-5.76 to 20+/-11.98 (p<0.01) and from 32+/-9.13 to 19 +/-
      14.29 (p<0.05), respectively. Also, mean scores on the Hamilton Anxiety Rating
      Scale and Negative Symptom Scale declined significantly from 104+/-53.62 to 57+/
      36.41 (p<0.01) and from 57+/-15.38 to 33+/-18.8 (p<0.05), respectively. There
      were no statistical differences before and after surgery for Young's Mania Rating
      Scale, p>0.1. Using the CGPSS, 68.8% of patients had a marked response (CGPSS of
      >or=3), 18.9% of patients had a possible response (CGPSS of 2), and 12.6% did not
      improve or became worse (CGPSS of 0 or 1). There was no surgical mortality and
      only three patients experienced temporary minor complications. Based on these
      nine comprehensive psychiatric test evaluations, limbic leukotomy is an effective
      procedure for long-term treatment of severe, intractable major affective
      disorders, with no significant side effects. The results of the psychiatric tests
      carried out during the 7 years of follow-up were constant and stable. The current
      findings demonstrate that depression, anxiety, and negative symptoms are
      significantly reduced by limbic leukotomy, but mania and active symptoms are not.
      Surgical intervention remains an important therapeutic option for the treatment
      of major affective disorders, and is probably underused.

PMID- 18068370
TI  - Metalloids: essential, beneficial or toxic? Major intrinsic proteins sort it out.
AB  - Major intrinsic proteins (MIPs) are a family of selective membrane channels
      comprising water-channelling aquaporins and glycerol-channelling
      aquaglyceroporins. Recently, several MIPs within all domains of life were shown
      to facilitate the diffusion of reduced and non-charged species of the metalloids
      silicon, boron, arsenic and antimony. Metalloids encompass a group of
      biologically important elements ranging from the essential to the highly toxic.
      Consequently, all organisms require efficient membrane transport systems to
      control the exchange of metalloids with the environment. Recent genetic evidence
      has demonstrated a crucial role for specific MIPs in metalloid homeostasis. We
      propose that specific MIPs represent an ancient and indispensable transport
      mechanism for metalloids, which suggests that they could be potential
      pharmacological targets.

PMID- 18068371
TI  - Low molecular weight lignin suppresses activation of NF-kappaB and HIV-1
      promoter.
AB  - Human immunodeficiency virus type 1 (HIV-1) is a cytopathic retrovirus and the
      primary etiological agent of acquired immunodeficiency syndrome (AIDS) and
      related disorders. In cells chronically infected with HIV-1, nuclear factor
      kappaB (NF-kappaB) activation by external stimuli such as tumor necrosis factor
      alpha (TNFalpha) augments replication of HIV-1. NF-kappaB involves in many
      diseases such as inflammation, cancer, and Crohn's disease. In this paper, we
      exhibit that (i) HIV-1gene expression was inhibited by lignin, (ii) fraction of
      small molecular mass in HBS lignin (less than 0.5kDa) had stronger inhibitory
      effects than large molecular mass (more than 1.3kDa), (iii) lignin also inhibited
      activation of NF-kappaB induced by TNFalpha, (iv) among six lignin dimer-like
      compounds, compound 6 containing beta-5 bond has more potent inhibitory activity
      than compounds 1, 2, 3, 4 and 5, which contain beta-1, beta-O-4, 5-5, or beta
      beta structural units. These results suggested that small molecules of lignin
      inhibit HIV-1 replication through suppression of HIV-1 transcription from LTR
      including activation via NF-kappaB. Low molecular lignin may be a beneficial
      material or drug leads as a new class for AIDS and NF-kappaB-related diseases.

PMID- 18068372
TI  - Study of mean absorptive potential using Lenz model: toward quantification of
      phase contrast from an electrostatic phase plate.
AB  - An electrostatic phase plate can provide better phase contrast, a fact that plays
      a promising role for the high-resolution observation of specimens containing
      light elements. However, in order to quantify the "phase" contrast from images
      recorded using the phase plate, the "absorption" (or scattering) contrast arising
      from electrons scattered elastically and inelastically outside of the phase-plate
      ring must be analyzed. Angular distributions of the elastic and inelastic
      scattering are predicted using the Lenz model. The mean absorptive potential,
      V(o) serving as an index for the contribution of "absorption" contrast, is
      calculated from the reciprocal mean free path of elastic and inelastic
      scattering, and is verified experimentally. The mean absorptive potential of a
      particular phase plate with inner and outer radii of 0.25microm
      (theta(1)=0.09mrad) and 1mum (theta(2)=0.4mrad), respectively, is approximately
      0.11eV for carbon and is equivalent to that of an objective aperture of semiangle
      17mrad (cutoff frequency 6.7nm(-1)).

PMID- 18068373
TI  - Direct determination of uranium and co-extracted elements in the organic phases
      (D2EHPA/TOPO, TBP, TDA) in kerosene by TXRF technique.
AB  - The total reflection X-ray fluorescence (TXRF) spectrometry was used for direct
      determination of uranium concentration in the organic phase di-(2-ethyl hexyl)
      phosphoric acid and trioctyl phosphine oxide (D(2)EHPA-TOPO)/kerosene, which
      resulted from first and second cycles of uranium extraction from wet-process
      phosphoric acid. The TXRF measurements were performed using gallium as an
      internal standard. A linear relationship between relative intensity of uranium
      vs. gallium (I(U)/S(Ga)) against uranium concentration has been obtained. Four
      calibration curves, 0-5, 5-100, 100-1000 and 1000-7000 microgmL(-1), according to
      uranium concentration in the studied samples, were constructed. The detection
      limit was found to be 0.15 microgmL(-1). The effect of D(2)EHPA and TOPO
      concentration in kerosene on uranium determination was considered. The TXRF
      spectrometry was also applied for the multi-elemental analysis of the co
      extracted impurities with uranium, such as (Fe, Ni, Cu and Zn) in the organic
      phase, and four calibration curves, 0-500 microgmL(-1) Fe, 0-20 microgmL(-1) Ni,
      0-10 microgmL(-1) Cu and 0-20 microgmL(-1) Zn, according to Fe, Ni, Cu and Zn
      concentration in the studied samples were performed, respectively, using gallium
      as an internal standard. The obtained results using direct TXRF analysis method
      were in a very good agreement with those obtained by fluorometry method, which is
      suitable for aqueous solutions after stripping of uranium from the organic phase
      by 1M Na(2)CO(3).

PMID- 18068374
TI  - Impact of estimated glomerular filtration rate on the 15-year outcome after
      coronary artery bypass surgery.
AB  - OBJECTIVE: The aim of the present study was to evaluate the impact of estimated
      glomerular filtration rate (eGFR) on the 15-year outcome after coronary artery
      bypass surgery (CABG) in a community-wide population study. METHODS: Eight
      hundred and eighty-two patients who underwent CABG were included in this study.
      eGFR was estimated by the modified Modification of Diet in Renal Disease study
      equation. RESULTS: Among 30-day operative survivors, patients with eGFR<60
      ml/min/1.73 m(2) had significantly poorer overall survival (at 5, 10 and 15 year,
      84.7%, 63.5% and 43.8% vs 92.8%, 77.6% and 58.3%, respectively, p<0.0001). eGFR
      (HR 0.989, 95% CI 0.981-0.997, as well as eGFR<60 ml/min/1.73 m(2): HR 1.470, 95%
      CI 1.092-1.979) was an independent predictor of late all-cause mortality only
      when patients' age was excluded from the regression model. This was probably due
      to strong impact of age on eGFR. eGFR (HR 0.987, 95% CI 0.975-0.998, as well as
      eGFR<60 ml/min/1.73 m(2); HR 1.612, 95% CI 1.086-2.395) was an independent
      predictor of cardiovascular mortality secondary to ischemic heart disease or
      ischemic stroke. eGFR (HR 0.991, 95% CI 0.983-0.999, as well as eGFR<60
      ml/min/1.73 m(2): HR 1.396 95% CI 1.031-1.891) was an independent predictor of
      cardiovascular mortality and morbidity (myocardial infarction, stroke, need for
      redo CABG or PCI). When both preoperative serum creatinine and eGFR were included
      in the regression model, only eGFR was predictive of all-cause mortality,
      cardiovascular mortality and combined cardiovascular mortality and morbidity.
      CONCLUSIONS: This study showed that an eGFR<60 ml/min/1.73 m(2) is an important
      determinant of long-term outcome after isolated CABG. Since its predictive value
      seems to be superior to serum creatinine, eGFR may be useful to identify those
      patients undergoing CABG with subclinical chronic kidney disease.

PMID- 18068375
TI  - Interaction of 7-hydroxyflavone with human serum albumin: a spectroscopic study.
AB  - Numerous recent investigations have revealed that various synthetic as well as
      therapeutically active natural flavonoids possess novel luminescence properties
      that can serve as highly sensitive monitors for exploring their interactions with
      relevant physiological targets. Here we report a detailed study on the
      interactions of the model flavone, 7-hydroxyflavone (7HF) with the plasma protein
      human serum albumin (HSA), employing electronic absorption, fluorescence (steady
      state and time resolved) and induced circular dichroism (ICD) spectroscopy. The
      spectral data indicate that in the protein matrix, the neutral 7HF molecules are
      predominantly transformed to a conjugate anion (7HFA) by a proton abstraction in
      the ground state. The protein (HSA) environment induces dramatic enhancements in
      the fluorescence emission intensity, anisotropy (r) and lifetime (tau) values, as
      well as pronounced changes in the fluorescence excitation and emission profiles
      of the fluorophore. Moreover, evidence for efficient Forster type resonance
      energy transfer (FRET, from tryptophan to 7HFA) is presented, from which we infer
      that the binding site of 7HF in HSA is proximal (estimated distance, R=23.6A) to
      the unique tryptophan - 214 residue present in the inter-domain (between IIA and
      IIIA domains) loop region of the protein. The binding constant (K=9.44x10(4)M(
      1)) and the Gibbs free energy change (DeltaG=-28.33kJ/mol) for 7HFA-HSA
      interaction have been estimated from the emission data. Finally, the near-UV
      circular dichroism (CD) studies show that the electronic transitions of 7HF are
      strongly perturbed on binding to the chiral host (HSA), leading to the appearance
      of ICD bands. Implications of these results are discussed.

PMID- 18068376
TI  - Expression, purification and characterization of recombinant mitochondrial
      topoisomerase II of kinetoplastid Crithidia fasciculata in High-five insect
      cells.
AB  - Topoisomerase II of kinetoplastid parasites plays an important role in the
      replication of unusual networks of kinetoplast DNA (kDNA) and is a very useful
      target for antiparasitic drugs. In this study, we cloned full-length Crithidia
      fasciculata mitochondrial topoisomerase II gene into pFastBac-HTc vector and
      successfully expressed an active recombinant full-length mitochondrial
      topoisomerase II in Bac-to-Bac baculovirus expression system. A rapid and simple
      purification strategy was established by incorporating a FLAG-tag at the C
      terminus of the protein. The purified recombinant topoisomerase II showed a major
      single band on SDS-PAGE (>96% purity) and was verified through Western blot
      analysis. The recombinant full-length mitochondrial topoisomerase II exhibited
      decatenation, catenation and relaxation activity of type II topoisomerase as well
      as various sensitivities to a series of known topoisomerase inhibitors. These
      studies explore new way and lay groundwork to express all other similar full
      length kinetoplastid topoisomerases, it will also facilitate further elucidation
      of X-ray structure, catalysis mechanism of kinetoplastid topoisomerases and
      design of new antiparasitic drugs targeting kinetoplastid topoisomerases.

PMID- 18068377
TI  - Producing human mechano growth factor (MGF) in Escherichia coli.
AB  - MGF is a product of a unique muscle-specific splice variant of IGF1 gene (insulin
      like growth factor). Its peculiar feature is a specific E-peptide, a 16 a.a.
      strand at the C-terminus. MGF increases cellular proliferation and inhibits
      terminal differentiation of myoblasts necessary for the secondary myotube
      formation. Previous analysis of physiological effects of MGF was performed using
      indirect methods such as RT-PCR based examination of the transcript contents in
      normal tissues, adenovirus-mediated DNA delivery and synthetic E-domain
      administration. Here, we describe isolation and purification of recombinant MGF
      thus allowing for the first time the possibility of direct examining MGF effects.
      The recombinant MGF of directly examining--was expressed in Escherichia coli as
      inclusion bodies (about 100-200mg/l), purified and refolded. Biological activity
      of refolded MGF was analyzed in vitro in proliferation assays with normal human
      myoblasts. As a result of our work, it has become possible to generate a standard
      MGF control with characterized activity and a ready-to use MGF test-system
      neither of which have been previously described. Our data open opportunities for
      the future works on MGF characterization and to the development of a powerful and
      highly specific therapeutic agent potentially applicable for muscle growth up
      regulation, post-trauma muscle repair, age and hereditary myodystrophy mitigation
      and in sport medicine.

PMID- 18068378
TI  - Structural features of the single-stranded DNA-binding protein of Epstein-Barr
      virus.
AB  - We report the structural features of a C-terminal deletion construct of the
      Epstein-Barr virus single-stranded DNA-binding protein, Balf2 (Balf2DeltaC),
      which like the herpes simplex virus I encoded protein, infected cell protein 8
      (ICP8), binds non-sequence specifically to single-stranded DNA (ssDNA). ICP8, in
      the absence of ssDNA, assembles into long filamentous structures. Removal of the
      60 C-terminal amino acids of ICP8 (ICP8DeltaC) prevents the formation of such
      filaments, whereas addition of circular ssDNA to ICP8DeltaC induces formation of
      "super helical" filaments. Balf2DeltaC, which we show is a zinc-binding protein,
      does not form these filaments under the same conditions but does bind ssDNA in a
      weakly cooperative manner. Further structural comparison of both proteins in
      solution by small-angle X-ray scattering shows proteins with similar molecular
      envelopes. One major difference is the tendency of Balf2DeltaC to dimerize on
      different surfaces to that used for oligomerization when binding to ssDNA, and
      this may have implications for the mechanism of replication initiation.

PMID- 18068379
TI  - Identification of a new quaternary association for legume lectins.
AB  - Lotus tetragonolobus lectin (LTA) is a fucose-specific legume lectin. Although
      several studies report a diverse combination of biological activities for LTA,
      little is known about the mechanisms involved in l-fucosyl oligosaccharide
      recognition. The crystal structure of LTA at 2.0A resolution reveals a different
      legume lectin tetramer. Its structure consists of a homotetramer composed of two
      back-to-back GS4-like dimers arranged in a new mode, resulting in a novel
      tetramer. The LTA N-linked carbohydrate at Asn4 and the unusual LTA dimer-dimer
      interaction are related to its particular mode of tetramerization. In addition,
      we used small angle X-ray scattering to investigate the quaternary structure of
      LTA in solution and to compare it to the crystalline structure. Although the
      crystal structure of LTA has revealed a conserved metal-binding site, its l
      fucose-binding site presents some punctual differences. Our investigation of the
      new tetramer of LTA and its fucose-binding site is essential for further studies
      related to cross-linking between LTA and complex divalent l-fucosyl
      carbohydrates.

PMID- 18068381
TI  - Letter to the editor regarding "Delirium in vascular surgery". B. Balasundaram
      and J. Holmes. Eur J Vasc Endovasc Surg 2007;34:131-134.

PMID- 18068382
TI  - Mechanisms of pain referral in patients with whiplash-associated disorder.
AB  - The aim was to investigate the mechanisms of pain referral in patients with
      whiplash associated disorder. Pain was induced in 12 controls and 12 patients
      with whiplash associated disorder by intramuscular electrical stimulation in the
      infraspinatus muscle and the ipsilateral upper arm, i.e., the area where all
      subjects perceived referred pain during conditioning stimulation in the
      infraspinatus muscle. Conditioning stimulation amounted to a pain intensity rated
      as 2/10 and 4/10. During conditioning stimulation in the infraspinatus muscle,
      sensitivity to test stimuli was assessed in the referred pain area (i.e., upper
      arm) and vice versa. Test stimuli consisted of intramuscular electrical
      stimulation corresponding to innocuous perception threshold, electrical pain
      threshold, and pain intensities rated as 2/10, 4/10 and 6/10, respectively.
      Compared to controls, patients with whiplash associated disorder had increased
      pain sensitivity (p< or =0.01) and indicated larger areas of referred pain ((p<
      or =0.003) during stimulation at the infraspinatus muscle; p< or =0.03 during
      stimulation at the upper arm), including proximal referral of pain which was
      never reported by controls (p< or =0.05). During conditioning stimulation in the
      infraspinatus muscle (4/10) all subjects reported referred pain in the upper arm
      (corresponding to the test site) and innocuous perception thresholds
      (p<0.05)(patients) and electrical pain thresholds (p<0.001) (controls) decreased.
      Conditioning stimulation in the upper arm did not affect sensitivity to test
      stimuli in the infraspinatus muscle. In conclusion, patients with whiplash
      associated disorder had increased sensitivity to painful stimulation, reported
      larger areas of referred pain during the same subjectively painful conditioning
      stimulation (i.e., lower absolute stimulus intensities), including proximal pain
      referral which was never seen in controls, indicating aberrant processing of
      nociceptive input. The perceptual integration of nociceptive stimuli during
      simultaneous stimulation did not differ between groups suggesting that divergence
      of nociceptive input from the focal pain area leading to excitation of neurones
      with projected fields in the referred pain area most likely explains referred
      pain in both groups alike.

PMID- 18068383
TI  - Intrathecal antinociceptive interaction between the NMDA antagonist ketamine and
      the opioids, morphine and biphalin.
AB  - Biphalin is an opioid peptide analogue that currently is under clinical
      development as a new type of site-directed analgesic. In rats, the intrathecal
      (i.t.) analgesic potency of biphalin is 1000-fold greater than morphine. Such a
      high activity may reflect this compound's activation of three types of opioid
      receptors (mu, delta and kappa). NMDA receptors also play an important role in
      nociceptive processing. Therefore, we investigated in rats whether an NMDA
      antagonist may influence biphalin-induced antinociception. In the present study,
      ketamine was chosen because of the widespread safe use of this drug in clinical
      practice. I.t. application of ketamine alone had relatively little analgesic
      effect and its excitatory effects limited possible doses of the drug. Co
      administration of ketamine with biphalin or morphine produced markedly greater
      antinociception than biphalin or morphine alone in acute, thermal tail flick
      testing. These results suggest that NMDA antagonists may be useful potentiators
      of biphalin analgesia. Thus, to obtain the same spinal antinociceptive effect,
      lower doses of biphalin or morphine are required when ketamine is co
      administered.

PMID- 18068384
TI  - Recombinant perlucin nucleates the growth of calcium carbonate crystals:
      molecular cloning and characterization of perlucin from disk abalone, Haliotis
      discus discus.
AB  - Perlucin is well known as an important functional protein regulating pearl
      formation and shell biomineralization. In this study, we cloned the perlucin gene
      from the abalone Haliotis discus discus cDNA library. The full-length cDNA of the
      abalone H. discus discus perlucin gene consisted of 1038 bp nucleotides, encoding
      a putative signal peptide of 22 amino acids and a mature protein of 129 amino
      acids, which shared 55% identity with the homologous protein in greenlip abalone.
      The mature protein coding sequence was inserted into pMal-c2X expression vector
      and it expressed the recombinant protein in E. coli (Rosetta-gammi DE3). The
      maltose binding protein (MBP) fusion perlucin successfully promoted calcium
      carbonate precipitation and directed calcite crystal morphological modification.
      The successful expression of active recombinant perlucin suggested that
      recombinant perlucin gene transfer has the capability by color modification to
      improve the pearl's value. In the view of molecular structure, perlucin was a
      typical C-type lectin, which contained one highly conserved carbohydrate
      recognition domain. Reverse transcription polymerase chain reaction (RT-PCR)
      results showed that perlucin gene was expressed not only in the mantle, but also
      in the gill and digestive tract. Further characterization of perlucin in abalone
      non-self recognition and disease resistance is promising and anticipated.

PMID- 18068385
TI  - Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year
      experience (1993-2003).
AB  - BACKGROUND: Acute bacterial meningitis remains an important cause of morbidity,
      neurologic sequelae, and mortality in children in Latin America. METHODS: We
      retrospectively reviewed the hospital-based medical records of children diagnosed
      with acute bacterial meningitis, aged 1 month to 18 years, at a large inner city
      referral Hospital in Mexico City, for a 10-year period (1993-2003). To
      characterize the epidemiology, clinical features, and outcomes of acute bacterial
      meningitis, we subdivided our study into two time periods: the period prior to
      the routine use of Haemophilus influenzae type b (Hib) vaccine (1993-1998) and
      the period after the vaccine became available (1999-2003). RESULTS: A total of
      218 cases of acute bacterial meningitis were identified during the study period.
      The most frequently affected age group was that of children aged between 1 and 6
      months. Hib was the most commonly isolated pathogen, found in 50% of cases.
      However, its incidence declined significantly after the introduction of the
      combined diphtheria, tetanus, pertussis, hepatitis B, and conjugated Hib (DTP
      HB/Hib) pentavalent vaccine into the universal vaccination schedule for children
      in 1998. Streptococcus pneumoniae followed as the second most commonly isolated
      bacterial pathogen. Neisseria meningitidis was isolated in only a few cases,
      confirming the historically low incidence of this pathogen in Mexico. Identified
      risk factors for death were found to include the presence of septic shock and
      intracranial hypertension, but were not attributable to any particular bacterial
      pathogen. CONCLUSIONS: In our hospital, acute bacterial meningitis remains a
      severe disease with important sequelae and mortality. The incidence of Hib
      meningitis cases has declined since the introduction of the Hib vaccine. However,
      S. pneumoniae persists as an important cause of bacterial meningitis,
      highlighting the need for the implementation of vaccination policies against this
      pathogen.

PMID- 18068386
TI  - French medical practice in type 2 diabetes: the need for better control of
      cardiovascular risk factors.
AB  - AIMS: In type 2 diabetes (T2D), to describe treatments to prevent cardiovascular
      disease, to compare current practice to French guidelines, and to identify
      factors associated with recommended treatments. METHODS: In the Echantillon
      National Temoin Representatif des Personnes Diabetiques (ENTRED) study, 10,000
      adults treated for diabetes (any type) were randomly selected from the French
      National Health Insurance System database. Deliveries during the last quarter of
      2001 of treatments to prevent cardiovascular disease were extracted.
      Questionnaires were mailed to these people and their care providers. Final
      populations included 3324 people with T2D and their 1553 care providers. RESULTS:
      Overall, 18% reported coronary heart disease (CHD) and 44% others were classified
      as having a high cardiovascular risk; 68% received one or more antihypertensive
      treatment: ACE inhibitor/angiotensin receptor blocker (ARB), 44%; diuretic, 35%;
      calcium channel blocker, 25%; beta-blocker, 24%. Among those receiving
      antihypertensive treatment, 59% had blood pressure greater than 130/80mmHg.
      Overall, 42% received a hypolipidaemic treatment: statin, 25%; fibrate, 18%.
      About half the people with a high cardiovascular risk had LDL cholesterol greater
      than 1g/L, but only 32% were given a statin. Among people with an abnormal
      albumin/creatinine ratio (11%), 59% received an ACE inhibitor/ARB. Among those
      with CHD, 35% received the two treatments recommended in 1999 (beta-blockers and
      antiplatelet agents); in multivariate analyses, this two-treatment delivery was
      positively associated with male gender, self-reported hypertension and consulting
      a cardiologist. CONCLUSION: Cardiovascular risk profiles reported by providers in
      T2D people are high. Despite recent progress, there is a need for major
      improvement in practices intended to prevent cardiovascular disease in these
      people, especially in those at greatest CHD risk.

PMID- 18068387
TI  - Virulence and pathogenicity patterns of Trypanosoma brucei gambiense field
      isolates in experimentally infected mouse: differences in host immune response
      modulation by secretome and proteomics.
AB  - Human African trypanosomiasis is characterised by an important clinical
      diversity. Although Trypanosoma brucei gambiense field stocks isolated from
      patients in the same focus did not exhibit apparent genetic variability, they
      showed marked differences in terms of virulence (capacity to multiply inside a
      host) and pathogenicity (ability of producing mortality) in experimental murine
      infections. Two strains exhibiting opposite pathogenic and virulence properties
      in mouse were further investigated through their host-parasite interactions. In
      vitro, parasite bloodstream forms or soluble factors (or secretome) from both
      strains induced macrophage arginase as a function of their virulence. Arginase
      expression, a hallmark of macrophage alternative activation pathway, favours
      trypanosome bloodstream forms development. Moreover, a comparative proteomic
      study of the trypanosome stocks' secretomes evidenced both a differential
      expression of common molecules and the existence of stock specific molecules.
      This highlighted the potential involvement of the differential expression of the
      same genome in the diverse infectious properties of trypanosomes.

PMID- 18068388
TI  - Borrelia burgdorferi inhibits human neutrophil functions.
AB  - Outer surface proteins OspA and OspB are among the most prominent Borrelia
      burgdorferi surface molecules. We constructed OspAB and OspA complementation
      mutants of B. burgdorferi Osp-less strain B313 and investigated the role of these
      surface proteins in the interactions of B. burgdorferi, human neutrophils and the
      complement system. We found that (1) OspB inhibits the phagocytosis and oxidative
      burst of human neutrophils at low serum concentrations, whereas OspA induces the
      oxidative burst in neutrophils; (2) OspB may have an inhibiting role in serum
      sensitivity and complement activation; (3) all studied strains inhibit the
      chemotaxis of human neutrophils specifically towards fMLP but not towards C5a,
      regardless of their Osp expression. These results suggest that although OspA and
      OspB are co-ordinately transcribed, they differ in their effects on human
      neutrophil functions. Our findings suggest that B. burgdorferi exploits a wide
      variety of immune evasion mechanisms, besides previously documented complement
      resistance, to survive in the vertebrate host.

PMID- 18068389
TI  - Inactivation of the Mycobacterium tuberculosis fadB4 gene results in increased
      virulence in host cell and mice.
AB  - The genome of Mycobacterium tuberculosis encodes many proteins involved in fatty
      acid metabolism, a subset of which are required for virulence. The Mycobacterium
      tuberculosis fadB4 gene, which shares strong similarity with oxidoreductases and
      fatty acid synthases, is up-regulated during infection of macrophages and is
      predicted to protect the bacterium from the hostile environment of the host cell.
      In order to determine if fadB4 plays a role in the virulence of M. tuberculosis,
      we constructed a M. tuberculosis mutant in which the fadB4 had been disrupted
      (DeltafadB4). Surprisingly, DeltafadB4, grew more rapidly in host cells compared
      to wild-type M. tuberculosis or the DeltafadB4 or the gene-disrupted strain
      complemented with fadB4. In addition, macrophages infected with DeltafadB4
      displayed reduced secretion of the cytokine TNF-alpha, suggesting a role for the
      FadB4 protein in influencing the pro-inflammatory host response to M.
      tuberculosis. After infection of mice, DeltafadB4 demonstrated an increased
      replication at early time-points post-infection compared to the growth of wild
      type M. tuberculosis. This increased capacity of DeltafadB4 to replicate in vivo
      was reflected in the decreased time to death of immuno-deficient RAG-1(-/-) mice
      infected with M. tuberculosis lacking the fadB4 gene. Therefore fadB4 is part of
      the family of genes whose expression serves to regulate the virulence of M.
      tuberculosis within the host.

PMID- 18068390
TI  - Differential interaction of bacterial species from the Burkholderia cepacia
      complex with human airway epithelial cells.
AB  - To increase knowledge of the pathogenic potential of the Burkholderia cepacia
      complex (BCC), we investigated the effects of reference strains of the nine BCC
      species on human bronchial epithelial cells in vitro. B. multivorans exhibited
      the highest rates of adherence to and internalization by host cells. Two out of
      three clinical isolates recovered from cystic fibrosis patients confirmed the B.
      multivorans high adhesiveness. All four B. multivorans isolates exhibited an
      aggregated pattern of adherence but any of them expressed cable pili. When
      bacteria were centrifuged onto cell cultures to circumvent their poor
      adhesiveness, B. pyrrocinia exhibited the highest internalization rate, followed
      by B. multivorans. The percentages of apoptotic cells in cultures infected with
      B. cepacia, B. multivorans, B. cenocepacia (subgroups IIIA and IIIB), B. stabilis
      and B. vietnamiensis were significantly higher than in control non-infected
      cultures. All nine BCC species triggered a similar release of the inflammatory
      cytokine IL-8, that was not reduced by cell treatment with cytochalasin D. Hence,
      our data demonstrate, for the first time, that all BCC species exhibit a similar
      ability to induce the expression of host immune mediators whereas they differ on
      their ability to adhere to, invade and kill airway epithelial cells.

PMID- 18068391
TI  - Trypanosoma cruzi induces changes in cardiac connexin43 expression.
AB  - Gap junction proteins (connexins) are required for myocardial function, since
      they allow intercellular transmission of current carrying ions and signaling
      molecules. Previous studies demonstrated that rat cardiac myocytes infected with
      Trypanosoma cruzi lost gap junctional communication and decreased automaticity.
      We infected mouse cardiac myocytes with trypomastigotes of the Y strain of T.
      cruzi and observed alterations in connexin43 (Cx43) distribution. One hour post
      infection Cx43 levels were significantly increased. However, at longer time
      points post infection there was a significant loss of Cx43 staining in membranes
      of infected cardiac myocytes. Interestingly, there was also a significant
      reduction in myocardial Cx43 protein levels during acute infection. These data
      indicate that T. cruzi infection alters Cx43 expression both in vitro and in
      vivo. Disruptions in Cx43 may contribute to the pathogenesis of cardiac
      electrical alterations observed in T. cruzi infection.

PMID- 18068392
TI  - Human chitotriosidase is expressed in the eye and lacrimal gland and has an
      antimicrobial spectrum different from lysozyme.
AB  - Chitotriosidase is a chitinolytic enzyme expressed by maturing macrophages and
      preformed in neutrophil granules, suggesting a role in antimicrobial defence.
      Although available evidence supports a role in anti-fungal immunity, there is a
      lack of an obvious phenotype in humans homozygous for a mutation which renders
      chitotriosidase inactive. This may be explained by compensatory effects of
      enzymes co-expressed with chitotriosidase, such as lysozyme. We have found that
      chitinase is highly expressed in mouse and human eye, particularly in lacrimal
      glands. Chitotriosidase is the only member of the chitinase/chilectin gene
      cluster expressed in the murine eye. As lacrimal glands also produce lysozyme, we
      have asked whether chitotriosidase, in addition to its documented anti-fungal
      effects, has synergistic anti-bacterial properties with lysozyme. The effect of
      recombinant chitotriosidase on the growth of five Gram-positive (Bacillus cereus,
      Bacillus subtilis, Listeria innocua, Staphylococcus aureus and Staphylococcus
      aureus OatA(+/-)) and two Gram-negative strains (Escherichia coli and Pseudomonas
      aeruginosa), were tested in a luminometric assay. Recombinant chitotriosidase did
      not inhibit bacterial growth and did not synergize with lysozyme. Though the
      expression of chitotriosidase in the eye supports a role in innate immunity, the
      antimicrobial spectrum appears to be complementary to lysozyme and may indeed be
      limited to fungi.

PMID- 18068393
TI  - Antisynthetase syndrome with refractory polyarthritis and fever successfully
      treated with the IL-1 receptor antagonist, anakinra: A case report.

PMID- 18068394
TI  - Low back pain with radiculopathy in hospital outpatients in Lome (Togo).

PMID- 18068395
TI  - Superior vena cava syndrome without thrombosis revealing Behcet's disease: Two
      cases.
AB  - Superior vena cava (SVC) thrombosis is a rare but well-recognized manifestation
      of Behcet's disease, whereas SVC syndrome due to vasculopathy, without evidence
      of thrombosis, has only been described a single time in the literature. We report
      two cases of this exceptional association. The two patients presented with
      swelling of the face and oral aphtosis, the SVC stenosis was evidenced by angio
      CT and classical cavography. In each case, a combination of anticoagulant and
      immunosuppressive (corticosteroids and azathioprine) treatments allowed a
      significant improvement of SVC diameter. In one of the patients, an angioplasty
      of SVC was also performed. We believe there is a continuum between non
      obstructive and obstructive vasculopathy (thrombosis) of SVC. Inflammatory
      vascular injury secondary to vasculitis is considered to be the primary reason
      for thrombosis in Behcet's disease. Thickening of the venous wall observed in our
      patients probably reflects this inflammatory vascular injury. In conclusion,
      Behcet's disease should be considered in the differential diagnosis of SVC
      syndrome not related to thrombosis.

PMID- 18068397
TI  - I'll Google that.

PMID- 18068398
TI  - Flash sterilization.

PMID- 18068400
TI  - Results of the 2007 AORN Salary Survey.
AB  - AORN conducted its fifth annual compensation survey for perioperative nurses in
      August of 2007. A multiple regression model was used to examine how a variety of
      variables including job title, education level, certification, experience, and
      geographic region affect nursing compensation. Comparisons between 2007 and
      previous years' data also are presented. The effects of other forms of
      compensation, such as on-call compensation, overtime, bonuses, and shift
      differentials on average base compensation rates are examined.

PMID- 18068401
TI  - Emerging technologies in the OR and their effect on perioperative professionals.
AB  - New and emerging technologies can help increase the quality of health care, but
      implementing these technologies in a perioperative setting can create many
      challenges. Practitioners need to be aware of premises underlying future trends
      in health care and the kinds of technological changes that they can expect.
      Robots, digital displays, patient tracking systems, artificial organs, and
      magnetic sensors are some of the emerging technologies that are changing the
      perioperative landscape. Practitioners must be prepared to implement strategies
      that address the practical aspects of integrating these new technologies into the
      perioperative area.

PMID- 18068402
TI  - The effects of electronic documentation in the ambulatory surgery setting.
AB  - Electronic documentation can improve organizational processes in health care
      settings and may be of particular benefit to ambulatory surgery centers. A
      decision support system (DSS) can be integrated with an electronic documentation
      system. A DSS can identify potential errors and deviations from best practices
      and provide electronic alerts for health care clinicians to support patient
      screening and care. Barriers to implementation of a DSS include practitioner
      noncompliance with alerts and limitations in system design. Nurses can be
      instrumental in overcoming the barriers that prevent some clinicians from
      adopting these useful information systems.

PMID- 18068403
TI  - Postoperative fever: to what is the body really responding?
AB  - The presence of a postoperative fever is not always indicative of an infectious
      process. Mild temperature elevation may be transient in nature and may arise from
      the body's response to tissue injury. Fevers that present from two to more than
      seven days after a surgical procedure may be caused by other physiological
      responses. Perioperative nurses can target nursing assessments according to the
      postoperative day on which the fever presents.

PMID- 18068404
TI  - A team training program using human factors to enhance patient safety.
AB  - Beginning in 2005, the aorn foundation and Safer Healthcare implemented a human
      factors program based on Crew Resource Management training in five diverse
      surgical facilities across the United States. Highly interactive, customized
      training sessions were designed to help clinicians standardize communication,
      enhance teamwork, implement preprocedure briefings and postprocedure debriefings,
      maintain situational awareness, and recognize red flags in the workplace.
      Pretraining and post-training surveys were used to determine the effectiveness of
      the program. Brief overviews from the participating facilities detail specific
      issues encountered in each setting.

PMID- 18068405
TI  - Risks associated with exposure to surgical smoke plume: a review of the
      literature.
AB  - Electrosurgery, laser ablation, and ultrasonic scalpel dissection create a
      gaseous by-product commonly referred to as surgical smoke or plume. Smoke
      evacuation devices have been shown to be effective in limiting exposure to the
      noxious odor and potential health hazards of smoke and plume; however, these
      devices have not been used routinely and consistently in many ORs. This article
      reviews five quantitative research studies that explore the characteristics of
      smoke plume produced during surgery and presents the evidence of the need for
      consistent use of smoke evacuation systems.

PMID- 18068406
TI  - Transforming the OR into a classroom: Live From ... Kidney Transplant.

PMID- 18068408
TI  - The 2008 perioperative nurses' goals for safety.

PMID- 18068411
TI  - [The double-cup carpus: a demonstration of the variable geometry of the carpus].
AB  - OBJECTIVES: The variable frontal geometry of the carpus has been known for many
      years, however there is no unanimity as to whether to describe the dynamic model
      of the carpus as comprising row or columnar functional units. The place of the
      scaphoid is also discussed. This study attempts to understand the organization
      and the composition of the functional units of the carpus. METHODS: We took
      radiographs of 40 normal right wrists in radial and ulnar deviation and measured
      the displacement in the coronal plane of each carpal bone except the pisiform. We
      measured the angular movements of each carpal bone compared to a vertical axis
      passing through the geometric centre of the carpus. This axis is parallel to the
      radial axis which is defined as the line joining the midpoints of the radius at 2
      and 5 cm proximal to the radial articular surface. We studied the movement of
      each row and each column. RESULTS: Recorded angular movements were the
      followings: scaphoid 26 degrees, lunate 28 degrees, triquetrum 29 degrees,
      trapezium 44 degrees, trapezoid 50 degrees, capitate 50 degrees, hamate 56
      degrees. Average angular movement within the first row is 27 degrees, within the
      second row is 50 degrees. Average angular movement within the radial column is 38
      degrees, middle column is 39 degrees, ulnar column is 42 degrees. CONCLUSIONS:
      The amplitude of movement are similar for the bones of each row, and different
      for the bones of each column. The bones of each row tend to move together and can
      alone account for all movements of the wrist. The movements measured between each
      column are torsional intrarow movements, allowing congruence between the two rows
      and the glenoid surface of the radius. The scaphoid movements are superposable
      with those of lunate and triquetrum. Scaphoid kinematics joins the first row.
      Radio-ulnar deviation of the wrist is shared equally between the radiocarpal and
      midcarpal joints. This sharing of wrist movement between the two rows constitutes
      for us a double cup carpal model.

PMID- 18068417
TI  - Type I interferon as a stimulus for cross-priming.
AB  - Type I interferon (IFN-alpha/beta) is induced rapidly by infection and is well
      recognised for its crucial role in innate defence. However, it is evident that
      IFN-alpha/beta also serves as a signal for the generation of adaptive immune
      responses. In this review, we focus on the involvement of IFN-alpha/beta in the
      induction of CD8+ T cell responses by cross-priming.

PMID- 18068419
TI  - Performance evaluation of a medical robotic 3D-ultrasound imaging system.
AB  - 3D-ultrasound (US) imaging systems offer many advantages such as convenience, low
      operative costs and multiple scanning options. Most 3D-US freehand tracking
      systems are not optimally adapted for the quantification of lower limb arterial
      stenoses because their performance depends on the scanning length, on ferro
      magnetic interferences or because they require a constant line of sight with the
      US probe. Robotic systems represent a promising alternative since they can
      control and standardize the 3D-US acquisition process for large scanning
      distances without requiring a specific line of sight. The performance of a new
      prototype medical robot, in terms of positioning and inter-target accuracies
      (i.e., difference between measurements and ground truth values) was evaluated
      with a lower-limb mimicking phantom throughout the robot workspace. The
      teach/replay repeatability (i.e., difference between taught and replayed points)
      was also assessed. A mean positioning accuracy between 0.46 mm and 0.75 mm was
      found on all scanning zones. The mean inter-target distance accuracy varied
      between 0.26 mm and 0.61 mm. Teach/replay repeatability below 0.20mm was also
      obtained. Additionally, a 3D reconstruction of in-vitro stenoses was performed
      with the robotic US scanner. The quantification error of a 80% area reduction
      (AR) stenosis was 3.0%, whereas it was -0.9% for a less severe 75% AR stenosis.
      Altogether, these results suggest that the robot may be of value for the clinical
      evaluation of lower limb vessels over long and tortuous segments starting from
      the iliac artery down to the popliteal artery below the knee.

PMID- 18068420
TI  - Chromosome aberration and micronucleus frequencies in Allium cepa cells exposed
      to petroleum polluted water--a case study.
AB  - In the present study, we applied Chromosome Aberration (CA) and Micronucleus (MN)
      tests to Allium cepa root cells, in order to evaluate the water quality of Guaeca
      river. This river, located in the city of Sao Sebastiao, SP, Brazil, had been
      affected by an oil pipeline leak. Chemical analyses of Total Petroleum
      Hydrocarbons (TPHs) and Polycyclic Aromatic Hydrocarbons (PAHs) were also carried
      out in water samples, collected in July 2005 (dry season) and February 2006
      (rainy season) in 4 different river sites. The largest CA and MN incidence in the
      meristematic cells of A. cepa was observed after exposure to water sample
      collected during the dry season, at the spring of the river, where the oil leak
      has arisen. The F(1) cells from roots exposed to such sample (non-merismatic
      region) were also analyzed for the incidence of MN, showing a larger frequency of
      irregularities, indicating a possible development of CA into MN. Lastly, our
      study reveals a direct correlation between water chemical analyses (contamination
      by TPHs and PAHs) and both genotoxic and mutagenic effects observed in exposed A.
      cepa cells.

PMID- 18068421
TI  - Spectroscopic investigations of Nd3+ doped flouro- and chloro-borate glasses.
AB  - Spectroscopic and physical properties of Nd3+ doped sodium lead flouro- and
      chloro-borate glasses of the type 20NaX-30PbO-49.5B2O3-0.5Nd2O3 (X=F and Cl) have
      been investigated. Optical absorption spectra have been used to determine the
      Slater Condon (F2, F4, and F6), spin orbit xi4f and Racah parameters (E1, E2, and
      E3). The oscillator strengths and the intensity parameters Omega2, Omega4 and
      Omega6 have been determined by the Judd-Ofelt theory, which in turn provide the
      radiative transition probability (A), total transition probability (A(T)),
      radiative lifetime (tauR) and branching ratio (beta) for the fluorescent level
      4F3/2. The lasing efficiency of the prepared glasses has been characterized by
      the spectroscopic quality factor (Omega4/Omega6), the value of which is in the
      range of 0.2-1.5, typical for Nd3+ in different laser hosts. Nephelauxetic effect
      results in a red shift in the energy levels of Nd3+ for chloroborate glass. The
      radiative transition probability of the potential lasing transition 4F3/2-
      >4I11/2 of Nd3+ ions is found to be higher for flouroborate as compared to
      chloroborate glass.

PMID- 18068422
TI  - FT-IR spectroscopic investigation of some Hofmann type complexes: M(1
      phenylpiperazine)2Ni(CN)4 (M=Ni, Co, Cd, Pd or Mn).
AB  - New Hofmann type complexes in the form of M(pp)(2)Ni(CN)(4) (where pp=1
      phenylpiperazine and M=Ni, Co, Cd, Pd or Mn) have been prepared in powder form
      and their infrared spectra have been reported in the range of (4000-400) cm(-1).
      The thermal behaviours of these complexes have been investigated by differential
      thermal analysis (DTA) and thermo-gravimetric analysis (TGA). Ni(pp)(2)Ni(CN)(4)
      complex has been examined via transmission electron microscope (TEM). The results
      suggest that these compounds are similar in structure to Hofmann type complexes
      and their structures consist of polymeric layers |M-Ni(CN)(4)|(infinity) with the
      pp molecule bounded to the metal atom (M).

PMID- 18068423
TI  - DFT study of structural, electronic, vibrational, and magnetic properties of the
      chirality cage-like molecule C24O12.
AB  - Bonding, vibrational and magnetic properties of the cage-like molecule C24O12 are
      studied by DFT calculations. Infrared- and Raman-active vibrational frequencies
      of the cage-like molecule C24O12 are assigned. Two 13C and one 17O nuclear
      magnetic resonance (NMR) spectral signals of the cage-like molecule C24O12 are
      characterized. Heat of formation of the cage-like molecule C24O12 is estimated.
      Compared to C60 and the cage-like molecule C24O12, only from the thermodynamic
      points of view, C24O12 is more stable than C60. Thus we believe that the cage
      like molecule C24O12 has sufficient stability to allow its experimental
      preparation. We proposed that it could be synthesized by using the condensation
      of molecules C6(OH)6 and C12Cl12. Since the symmetry of C24O12 is D6, it is a
      chiral molecule.

PMID- 18068424
TI  - The effect of Trp83 mutant on the properties of CopC.
AB  - CopC, a protein involved in copper resistance, is essentially constituted by two
      sheets forming a Greek key beta barrel motif. The aromatic ring of Trp83,
      sandwiched between the two beta sheets, has numerous contacts with residues in
      strands beta and stabilizes the protein fold. In the paper Trp83 was mutated to
      Leu to study the effect of this mutation on CopC by means of fluorescence spectra
      and UV spectra. The experiments indicate that the mutation bind Cu(2+) with a
      decreased formation constant of 3.95 x 10(11) M(-1) in 20 mM PB buffer at pH 7.0;
      mutagenesis make hydrophobic region to be exposed to an extent. Compared with the
      wild, thermal stability of the mutant was shown to decrease by stronger
      fluorescence of TNS at 80 degrees C. The important role of aromatic residue in
      structure is exhibited.

PMID- 18068425
TI  - Catalytic reduction of pralidoxime in pharmaceuticals by macrocyclic Ni(II)
      compounds derived from orthophthalaldehyde.
AB  - Efficient catalytic method for the reduction of pralidoxime to its amine
      derivative by macrocyclic Ni(II) compounds has been developed. Ten macrocyclic
      Schiff base Ni(II) compounds were synthesized via non-template synthesis by
      treating the corresponding macrocycles with nickel chloride in 1:1 ratio. The
      resulting compounds were characterized by elemental, IR, (1)H NMR, (13)C NMR,
      mass, electronic spectra, conductance, magnetic, thermal studies and their
      structures have been proposed. These compounds were used as catalysts for the
      reduction of pralidoxime to its amino derivative. The reduced pralidoxime was
      also characterized by spectral analysis and catalytic cycle has been established.
      The reduced product was determined spectrophotometrically by treating with
      ninhydrin reagent and the percent yields were found to be in the range of 75.12
      82.36%.

PMID- 18068426
TI  - Synthesis and spectral characterization of 2'-hydroxy chalconate complexes of
      ruthenium(II) and their catalytic and biological applications.
AB  - The reactions of [RuHCl(CO)(B)(EPh3)2] (B=EPh3 or pyridine; E=P or As) and 2'
      hydroxychalcones in 1:2 ratio led to the formation of [Ru(CO)(B)(L)2] (B=PPh3,
      AsPh3 or Py; L=2'-hydroxychalcones). The new complexes have been characterized by
      analytical and spectral (IR, electronic and 1H NMR) data. They have been assigned
      an octahedral structure. The new complexes were found to catalyze the oxidation
      of alcohols to aldehydes using N-methylmorpholine-N-oxide as co-oxidant. All the
      new complexes were found to be active against bacteria such as E. coli,
      Salmonella typhi and fungi Aspergillus niger. The activity was compared with
      standard Streptomycin or Bavistin.

PMID- 18068427
TI  - Computer-aided diagnosis in chest radiography for detection of childhood
      pneumonia.
AB  - OBJECTIVES: This article presents a novel approach based on computer-aided
      diagnostic (CAD) scheme and wavelet transforms to aid pneumonia diagnosis in
      children, using chest radiograph images. The prototype system, named Pneumo-CAD,
      was designed to classify images into presence (PP) or absence of pneumonia (PA).
      MATERIALS AND METHODS: The knowledge database for the Pneumo-CAD comprised chest
      images confirmed as PP or PA by two radiologists trained to interpret chest
      radiographs according to the WHO guidelines for the diagnosis of pneumonia in
      children. The performance of the Pneumo-CAD was evaluated by a subset of images
      randomly selected from the knowledge database. The retrieval of similar images
      was made by feature extraction using wavelets transform coefficients of the
      image. The energy of the wavelet coefficients was used to compose the feature
      vector in order to support the computational classification of images as PP or
      PA. Methodology I worked with a rank-weighted 15-nearest-neighbour scheme, while
      methodology II employed a distance-dependent weighting for image classification.
      The performance of the prototype system was assessed by the ROC curve. RESULTS:
      Overall, the Pneumo-CAD using the Haar wavelet presented the best accuracy in
      discriminating PP from PA for both, methodology I (AUC=0.97) and methodology II
      (AUC=0.94), reaching sensitivity of 100% and specificity of 80% and 90%,
      respectively. CONCLUSION: Pneumo-CAD could represent a complementary tool to
      screen children with clinical suspicion of pneumonia, and so to contribute to
      gather information on the burden of-pneumonia estimates in order to help guide
      health policies toward preventive interventions.

PMID- 18068428
TI  - Residual deficits from concussion as revealed by virtual time-to-contact measures
      of postural stability.
AB  - OBJECTIVE: Traumatic brain injury (TBI), including mild traumatic brain injury
      (MTBI), commonly known as a "concussion", is still one of the most puzzling
      neurological disorders and least understood injuries facing sport medicine and
      the scientific community [Cantu R. Concussion assessment Ongoing controversy. In:
      Slobounov S, Sebastianelli W, editors. Foundations of sport-related brain
      injuries. New York: Springer Press; 2006. p. 87-111.]. It was our primary
      objective to assess the dynamic properties of postural control in subjects prior
      to and after sport-related MTBI using the traditional center of pressure (COP)
      and virtual time-to-contact (VTC) measures. METHODS: We assessed 12 student
      athletes prior to and 30 days after they suffered sport-related MTBI on a number
      of standing still and dynamic postural tasks. All subjects were clinically
      asymptomatic at day 30 of testing and were cleared for full sport participation
      based upon neurological and neuropsychological assessments, as well as clinical
      symptoms resolution. RESULTS: The findings showed: (1) no significant differences
      for any of the standard COP-based measures of postural control (i.e., 90% ellipse
      COP area, COP velocity and Stability Index) as a function of testing day (prior
      to and 30 days post-injury, p>.05); (2) no differences in terms of VTC shape,
      distribution and nominal values before and after concussion during standing still
      postural tasks regardless of vision conditions, p>.05; and (3) there were
      significant alterations in VTC in terms of absolute values, range of VTC at the
      deflection points and mode at the day 30 post-injury. CONCLUSIONS: The deficits
      in VTC control are indicative of residual postural abnormality in subjects
      suffering from mild traumatic brain injuries and provide further evidence that
      VTC is used to regulate dynamic postural movement. SIGNIFICANCE: The results show
      that residual postural abnormalities in concussed individuals may be undetected
      using conventional research methods and the implications of this for clinical
      practice are discussed.

PMID- 18068429
TI  - Characterization of the 7-12 Hz EEG oscillations during immobile waking and REM
      sleep in behaving rats.
AB  - OBJECTIVE: The aim of this study was to examine whether the mu rhythm is also
      seen in the EEG of alert, undrugged and freely moving rats. The mu rhythm is a
      salient neocortical synchrony with dominant frequency in the 8-13 Hz band,
      initially recorded over the parietal and frontal areas of humans and subsequently
      investigated in monkeys and cats using the term sensorimotor rhythm. In the rat,
      these oscillations have been described only at single-unit level in the
      trigeminal system or in the cerebellar hemispheres. METHODS: In order to identify
      this rhythm, according to the "functional topography" approach, we examined the
      shape, spectral content, spatial distribution in power spectra, and functional
      reactivity. Rats were implanted with multiple electrodes along the antero
      posterior axes. Monopolar recordings and simultaneous continuous 24-h video were
      taken in natural dark-light cycles for 6 consecutive days. Brain mappings based
      on quantitative spectral analysis were made. RESULTS: Spontaneous well-defined 7
      12 Hz EEG oscillations were found during immobile wakefulness and REM sleep.
      Comparable features of these patterns indicated that they are largely analogous
      to the mu rhythm. CONCLUSIONS: The conservation of mu rhythm in the EEG across
      mammalian species with different cortical extension suggests that it is
      functionally important. SIGNIFICANCE: Given the great interest aroused by the
      properties of the mirror neurons, reflected by the mu rhythm, the detailed
      characterization of this rhythm in rats during natural life may prove useful in
      prospective evolutionary studies.

PMID- 18068430
TI  - Combining the ventilatory response to exercise and peak oxygen consumption is no
      better than peak oxygen consumption alone in predicting mortality in chronic
      heart failure.
AB  - BACKGROUND: A low peak oxygen uptake (pVO(2)) and steep VE/VCO(2) slope are
      independently associated with a worse prognosis in patients with chronic heart
      failure (CHF). We wished to confirm whether combining these variables as a ratio
      would lead to a more accurate predictor of prognosis than using either alone.
      METHODS: 388 CHF patients completed a treadmill-based cardiopulmonary exercise
      test (CPET) to volitional exhaustion using a modified Bruce protocol. RESULTS:
      212 CHF patients completed the CPET with a peak RER >or= 1.0. Of these, 48
      patients died and one was transplanted during follow-up. In surviving patients,
      the median follow-up period was 42 months (IQR 34-49 months). The ratio VE/VCO(2)
      slope/pVO(2) was calculated for each individual and its ability to predict
      outcome compared with other variables. The Cox multivariable survival analysis
      showed that pVO(2) was the strongest independent predictor of mortality in CHF
      patients. CONCLUSION: Our study shows that the composite variable VE/VCO(2)
      slope/pVO(2) is a less effective prognosticator than pVO(2) alone in patients
      with CHF.

PMID- 18068431
TI  - Ile164 variant of beta2-adrenoceptor does not influence outcome in heart failure
      but may interact with beta blocker treatment.
AB  - BACKGROUND: The Ile164 variant of the beta2-adrenoceptor has been shown to alter
      cardiovascular phenotypes and adversely affect survival in heart failure
      patients. AIMS: We aimed to replicate this observation by genotyping a cohort of
      451 heart failure patients for the Ile164 polymorphism. METHODS: Patient outcome
      was recorded over a median follow-up period of 3.09 years, and genotypes were
      derived by multiplex amplification refractory mutation system PCR. RESULTS:
      Genotypes were obtained for 443 patients, and 3.2% of these (14 patients) were
      heterozygous for the Ile164 SNP. Demographic data, cardiac function and
      neurohormonal profiles did not differ between genotype groups. Ile164 genotype
      did not significantly affect survival in this cohort (Thr164 homozygotes 48.9%,
      Ile164 heterozygous 42.9%, p=0.66), although multivariate analysis suggested that
      beta-blocker treatment may negatively impact survival in the heterozygote group.
      CONCLUSION: This study suggests that the Ile164 polymorphism of the beta2
      adrenoceptor does not have a major impact on outcome in individuals with heart
      failure, although it's potential interaction with beta-blockers requires further
      examination.

PMID- 18068432
TI  - B-type natriuretic peptide levels in patients with functionally univentricular
      hearts after total cavopulmonary connection.
AB  - AIMS: To assess plasma B-type natriuretic peptide (BNP) levels in patients with
      univentricular hearts late after volume unloading by total cavopulmonary
      connection (TCPC). METHODS: Plasma BNP was measured by sandwich immunoassay in 67
      patients after a modified Fontan procedure. BNP levels were compared with age and
      sex-specific normal values, clinical and echocardiographic data, and results of
      exercise testing. RESULTS: BNP had a wide range of 5-290 pg/ml, but was normal in
      81% of patients, and median BNP was only 13 pg/ml. There was no difference
      between males and females, between patients with left or right ventricular
      morphology, and no correlation was found between BNP and age, post-operative
      follow-up period, maximum exercise capability, peak oxygen uptake, or blood
      oxygen saturation. New York Heart Association class I patients had lower BNP than
      class II patients (p=0.04). Plasma BNP concentration was positively correlated to
      the number of specific sequelae (r=0.59, p<0.001), and to severity of
      atrioventricular regurgitation (r=0.38, p=0.002). 5/13 patients with elevated BNP
      died during follow-up. CONCLUSION: BNP plasma concentration was normal in the
      majority of patients up to 15 years after TCPC. Elevated and increasing BNP
      levels were associated with increased morbidity and late mortality.

PMID- 18068433
TI  - Heart rate and blood lactate correlates of perceived exertion during small-sided
      soccer games.
AB  - The rating of perceived exertion (RPE) could be a practical measure of global
      exercise intensity in team sports. The purpose of this study was to examine the
      relationship between heart rate (%HR(peak)) and blood lactate ([BLa(-)]) measures
      of exercise intensity with each player's RPE during soccer-specific aerobic
      exercises. Mean individual %HR(peak), [BLa(-)] and RPE (Borg's CR 10-scale) were
      recorded from 20 amateur soccer players from 67 soccer-specific small-sided games
      training sessions over an entire competitive season. The small-sided games were
      performed in three 4min bouts separated with 3min recovery on various sized
      pitches and involved 3-, 4-, 5-, or 6-players on each side. A stepwise linear
      multiple regression was used to determine a predictive equation to estimate
      global RPE for small-sided games from [BLa(-)] and %HR(peak). Partial correlation
      coefficients were also calculated to assess the relationship between RPE, [BLa(
      )] and %HR(peak). Stepwise multiple regression analysis revealed that 43.1% of
      the adjusted variance in RPE could be explained by HR alone. The addition of
      [BLa(-)] data to the prediction equation allowed for 57.8% of the adjusted
      variance in RPE to be predicted (Y=-9.49-0.152 %HR(peak)+1.82 [BLa(-)], p<0.001).
      These results show that the combination of [BLa(-)] and %HR(peak) measures during
      small-sided games is better related to RPE than either %HR(peak) or [BLa(-)]
      measures alone. These results provide further support the use of RPE as a measure
      of global exercise intensity in soccer.

PMID- 18068434
TI  - Sustaining health promotion programs within sport and recreation organisations.
AB  - The involvement of the sport and recreation sector as a setting for health
      promotion is a new strategy implemented by health policy makers and strategic
      planners. Strategies to promote and sustain health promotion activities are
      important considering the risk that programs may cease after initial funding
      ends. This study explored the factors affecting the sustainability of a sport-
      and recreation-based health promotion program. A stratified sampling method was
      used to select four of the nine Regional Sports Assemblies (RSAs) that delivered
      a state-wide health promotion program funded by the Victorian Health Promotion
      Foundation in Australia. Data were collected from in-depth interviews with four
      Executive Officers (EOs) and focus group discussions with their Boards of
      Management. A sustainability checklist with pre-specified dimensions (e.g.
      organisational setting, broader community environment, and program design and
      implementation) guided data collection and analysis. The results showed that the
      organisational setting and the broader community environment supported program
      institutionalisation; whilst the design and implementation of the program worked
      against institutionalisation. The capacity of the organisations to generate new
      funds for the program was limited; the relationship between the central funding
      organisation and the Boards of Management was weak; and the program did not
      support the retention of staff. The engagement of sport and recreation
      organisations has potential to facilitate health promotion and public health. To
      enhance organisational capacity and achieve program sustainability, it is
      important that organisational processes, structures, and resources that support
      long-term health promotion practice are effectively and efficiently planned and
      managed.

PMID- 18068435
TI  - Pathologic stage migration has slowed in the late PSA era.
AB  - OBJECTIVES: Serum prostate specific antigen (PSA) screening has led to clinical
      and pathologic stage migration. We examined patients treated by radical
      prostatectomy between 1987 and 2005 to establish temporal trends in pathologic
      stage migration as assessed by the proportion of patients with nonorgan-confined
      disease (NOCD). METHODS: Step-sectioned prostatectomy specimens of 3364
      consecutively treated patients were evaluated by year. The data were modeled by
      joinpoint regression, and the optimal model was selected by a Bayesian
      information criterion. RESULTS: From 1987 to 2005, the population underwent
      pathologic stage migration toward more organ-confined tumors (P <0.0001). The
      proportion of patients with NOCD exhibited changes in trend at 1992 and 1995.
      After widespread implementation of PSA screening, stage migration accelerated
      between 1992 and 1995. Since 1995, stage migration has substantially slowed but
      continues at an annual change of -4.2% (P = 0.0027). CONCLUSIONS: The presence of
      NOCD at prostatectomy has declined substantially in the PSA era. Recent slowing
      in this trend suggests a diminishing effect of PSA screening on pathologic stage
      migration.

PMID- 18068436
TI  - Are doctors examining prostates in university hospital?
AB  - OBJECTIVES: We have observed that serum prostate-specific antigen (PSA) testing
      is commonly performed for prostate assessment or screening but use of digital
      rectal examinations (DREs) appears inconsistent. To better define suspected
      underperformance of DRE, we studied the frequency of combining DRE with PSA
      testing in prostate assessment. METHODS: We performed a retrospective study of
      197 consecutive patients at a single institution from January 2004 to June 2005
      for whom an in-patient urologist consultation was requested. The inclusion
      criteria were male patients aged 50 years or older with no history of prostate
      cancer. The mean age of the patients was 62.4 years. Documentation of DREs and
      PSA testing, reasons for the urologist consultation, and the teams responsible
      for the patient's hospital care were assessed by a single chart reviewer familiar
      with the setting and format of the hospital medical records. RESULTS: A total of
      89 patients (45.18%) had PSA test results, 50 (25.38%) had DRE findings, and 34
      (17.26%) had both DRE findings and PSA test results documented in the hospital
      medical record during their admission before the urologist consultation. Of 68
      surgical patients, 22 (32.35%) had undergone DRE compared with 28 medical
      patients (21.71%). More medical patients had had PSA testing than had surgical
      patients (48.06% versus 39.88%). CONCLUSIONS: Prostate cancer assessment or
      screening by combining DRE with PSA testing is often not done by doctors in a
      teaching university hospital. The underperformance of DRE not only deprives
      junior doctors of training but also leads to nondetection of some prostate cancer
      cases.

PMID- 18068437
TI  - Retrograde ureteral stents for extrinsic ureteral obstruction: nine years'
      experience at University of Michigan.
AB  - OBJECTIVES: To review our experience with retrograde ureteral stenting for
      extrinsic ureteral obstruction because previous reports have suggested only
      moderate success. METHODS: We performed a retrospective review of the course of
      patients who underwent retrograde ureteral stent placement from March 1996 to
      April 2005. The gathered clinical parameters included stent failure, which was
      defined as any ureteral unit (UU) that remained obstructed. RESULTS: A total of
      54 patients treated for extrinsic ureteral compression, representing 87 UUs, were
      followed for an average of 16 months (range 0.7 to 98) in successful cases. Of
      the stents, 68% were placed for malignancy, 23% for retroperitoneal fibrosis, and
      9% for benign masses. The overall success rate was 84%, with malignancy,
      retroperitoneal fibrosis, and benign masses having an 81%, an 85%, and a 100%
      success rate, respectively. Fourteen UUs failed, with a mean time to stent
      failure of 4.8 months (range 0.07 to 27). Multiple stents were placed in 54 UUs,
      with a mean of 5.5 stent exchanges, at a mean interval of 3.6 months. On
      univariate analysis, only greater posttreatment creatinine was associated with
      stent failure (P <0.01), although stents placed for localized disease tended to
      be more successful than those placed for regional disease (100% versus 81%, P =
      0.07). CONCLUSIONS: If initial stent placement was possible, extrinsic ureteral
      obstruction was managed successfully with retrograde ureteral stent placement in
      84% of cases. Because no preoperative characteristics could be identified, except
      for a trend toward less success in cases of regional disease, retrograde stenting
      can be considered first-line treatment in patients with extrinsic ureteral
      obstruction.

PMID- 18068438
TI  - Adrenal trauma: Elvis Presley Memorial Trauma Center experience.
AB  - OBJECTIVES: Adrenal gland injury is a potentially devastating event if
      unrecognized in the treatment course of a trauma patient. We reviewed our single
      center experience and outcomes in patients with adrenal gland trauma. METHODS: We
      performed a retrospective review of all patients presenting with trauma to the
      Regional Medical Center at Memphis who had adrenal gland injuries from January
      1991 through March 2006. Each chart was reviewed with attention to the
      demographics, associated injuries, complications, and outcomes. Patients were
      stratified into two subgroups according to age (35 years or younger and older
      than 35 years) to allow for an age-based comparison between the two groups.
      RESULTS: Of 58,000 patients presenting with trauma, 130 (0.22%) were identified
      with adrenal injuries, of which 8 (6.2%) were isolated and 122 (93.8%) were not.
      Of these 130 patients, 125 (96.2%) had their injury diagnosed by computed
      tomography and 5 (3.8%) had their injury diagnosed during exploratory laparotomy.
      Right-sided injuries predominated (78.5%), with six (4.6%) bilateral. Four
      patients (3.1%) underwent adrenalectomy. Seven patients (5.4%) with adrenal
      injuries died. One patient (0.77%) required chronic steroid therapy. Patients
      older than 35 years were more likely to have complications such as deep venous
      thrombosis, pneumonia, and urinary tract infections. Patient age of 35 years or
      younger was associated with a significantly increased incidence of liver
      lacerations. CONCLUSIONS: Adrenal gland injury is uncommon, although mostly
      associated with greater injury severity. Although adding to morbidity, most are
      self-limited and do not require intervention.

PMID- 18068439
TI  - Ureterocystoplasty is safe and effective in patients awaiting renal
      transplantation.
AB  - OBJECTIVES: Surgical outcomes and bladder function were assessed in a group of
      patients who had undergone ureterocystoplasty while awaiting renal
      transplantation. METHODS: An observational cohort study was performed. A chart
      review was performed of 16 patients who had undergone ureterocystoplasty between
      1997 and 2006. The postoperative assessment included measurement of bladder
      capacity and voiding cystourethrography findings. RESULTS: The median patient age
      at operation was 17 years (range, 3 to 44 years). The median follow-up was 38
      months (range, 3 to 60 months). All patients achieved continence. The median
      increase in bladder capacity was 162 mL (range, 65 to 265 mL), representing a
      median proportional increase of 226% (range, 167% to 340%) of the original
      bladder capacity. None of the patients developed vesicoureteral reflux. Only 4
      patients required subsequent intermittent catheterization to fully empty their
      bladders. Seven patients underwent renal transplantation within 3 to 7 months of
      ureterocystoplasty. CONCLUSIONS: Ureterocystoplasty in patients awaiting renal
      transplantation is safe and effective. Good results can be achieved when care is
      taken to preserve the blood supply of the ureter. The results of this study have
      confirmed the desirability of preserving the ureters in patients awaiting
      transplantation who might require bladder augmentation.

PMID- 18068440
TI  - Incidence of local recurrence and port site metastasis after laparoscopic radical
      nephroureterectomy.
AB  - OBJECTIVES: To address the incidence of local recurrence and port site metastasis
      in patients who underwent laparoscopic radical nephroureterectomy (RNU) for upper
      tract transitional cell carcinoma (TCC). METHODS: Between August 1993 and
      February 2006 116 laparoscopic RNU were performed in 115 patients at our
      institution. A traditional open excision, a laparoscopic stapler resection or a
      different approach was used for the management of the distal ureter in 76, 27,
      and 11 cases, respectively. Clinical follow-up as well as perioperative and
      pathologic data were retrospectively collected. RESULTS: Perioperative and
      pathologic data were available in all 116 cases. Clinical outcomes were available
      in 107 patients with a mean follow-up of 30.5 months (range 1 to 148). Six
      patients (5.6%) had a local recurrence develop, including 1 patient with port
      site metastasis (0.9%) at an average of 5.7 months. In 2 of these patients,
      violation of the ipsilateral urinary tract was noted perioperatively.
      CONCLUSIONS: We report, in this large single-center series of laparoscopic RNU, a
      low incidence of local recurrence. Our results confirm that a laparoscopic
      approach to upper tract TCC does not result in a clinically significant increased
      risk of tumor spillage provided that principles of oncologic surgery are
      followed.

PMID- 18068441
TI  - Retroperitoneoscopic partial nephrectomy using radiofrequency coagulation for
      small renal tumors.
AB  - OBJECTIVES: Adoption of laparoscopic partial nephrectomy (LPN) has been limited
      by lack of reliable hemostatic techniques. We evaluated radiofrequency
      coagulation (RFC) in obtaining hemostasis during LPN for small renal masses.
      METHODS: Over 4 years LPN was performed by a retroperitoneal approach in 11
      patients with solitary, predominantly exophytic renal tumors. A retroperitoneal
      approach was used in all patients. The renal hilum was not exposed. RF energy was
      delivered to coagulate the lesion and a margin of normal parenchyma. Tumors were
      excised together with at least a 0.5-cm margin of normal parenchyma, with the use
      of ultrasonic shears. RESULTS: Mean tumor size was 2.2 cm (range, 1.5 to 3.0).
      Mean operative time was 222 minutes (range, 130 to 305 minutes) and mean blood
      loss was 51 mL (range, 10 to 200 mL). During excision bleeding from the cut renal
      surface was minimal, and structure of the cortex and medulla still could be
      clearly distinguished after coagulation. No serious complications such as
      uncontrolled bleeding or urine leakage occurred. One patient had a thermal burn
      develop at the site of needle electrode insertion and hydronephrosis caused by
      pyeloureteral junction (PUJ) stricture. In follow-up, ranging from 8 to 53
      months, no local recurrence or distant metastasis was detected by computed
      tomography. CONCLUSIONS: Hemostatic capability of RFC is excellent, improving
      visibility and ease of operation during LPN, and eliminating need for hilar
      clamping. Further experience and advancement of RF technology will be needed for
      the application of this method to larger, centrally located tumors.

PMID- 18068442
TI  - Prospective randomized comparison of laparoscopic and hand-assisted laparoscopic
      radical nephrectomy.
AB  - OBJECTIVES: The majority of localized renal cancers are currently managed by
      laparoscopic radical nephrectomy, with or without the hand-assist device. In this
      prospective randomized study, we evaluated the patient outcomes with a standard
      laparoscopic radical nephrectomy (LRN) versus a hand-assisted laparoscopic
      radical nephrectomy (HALN). METHODS: Over a 3-year period, we randomly assigned
      21 patients with a localized renal mass of 10 cm or larger to a LRN group with
      intact specimen extraction or a HALN. The trocar size and sites, the position of
      the hand-assist device, and the specimen extraction sites were standardized.
      Patient characteristics, surgical complications, postoperative pain, and
      convalescence were evaluated. RESULTS: Twelve patients underwent LRN and 9
      patients underwent HALN. Both groups had similar body mass indices (BMI), mean
      tumor diameter (LRN, 5.8 cm; HALN, 5.6 cm), and American Society of
      Anesthesiologists (ASA) scores. The HALN cohort was significantly older (mean age
      = 68 years) than the LRN cohort (mean age = 54 years) (P = 0.019).
      Perioperatively, both groups had similar mean times to oral intake and discharge
      (LRN 2.6 days and HALN 3 days, P = 0.6). Although both groups reported similar
      postoperative pain scale scores on day 1, at 1 and 3 months. Two patients in each
      group had complications (LRN 16% and HALN 22%). CONCLUSIONS: In comparing HALN
      and LRN, there was no difference in the majority of operative and postoperative
      parameters, including hospital stay and postoperative pain. However, LRN patients
      had a significantly shorter convalescence with quicker return to normal
      activities and work than the HALN group. Part of the delay in long-term
      convalescence parameters may be due to the older patients in the HALN cohort.

PMID- 18068443
TI  - Renal medullary carcinoma: the Bronx experience.
AB  - OBJECTIVES: Renal medullary carcinoma (RMC) is a devastating and extremely rare
      malignancy primarily afflicting young men with sickle cell trait. We present our
      clinical experience with 9 cases of RMC during a 10-year period and briefly
      review the published data. METHODS: A retrospective chart review of 9 cases of
      RMC during a 10-year period at our institutions was performed. The clinical
      patient characteristics, presentations, treatments, and outcomes were recorded.
      The radiographic images and pathologic specimens were reviewed. Applicable
      studies were selected from a Medline search. RESULTS: All 9 patients had sickle
      cell trait, the male/female ratio was 6:3, and the age range was 13 to 31 years.
      All the patients presented with flank pain, two thirds had hematuria, and 3 of
      the 9 patients presented with a palpable mass. Eight of the nine tumors were
      right sided, ranging from 4 to 12 cm in the greatest diameter. Of the 9 patients,
      7 underwent radical nephrectomy. One patient was deemed to have unresectable
      disease by the operating surgeon, and one was given initial chemotherapy after
      biopsy of a metastatic lesion. The neoadjuvant therapies varied. Overall survival
      ranged from 4 to 16 months, with 2 patients still living at the last follow-up
      visit. CONCLUSIONS: Our urban setting likely explains our relatively large
      experience with this rare and extremely aggressive tumor. An early diagnosis is
      critical, and a high index of suspicion should be given to any individual with
      sickle cell trait and new-onset hematuria, especially in the setting of a right
      sided mass. Prospective trials are needed for chemotherapy/immunotherapy, because
      surgical intervention alone is inadequate.

PMID- 18068444
TI  - A contemporary evaluation of the auditory hazard of extracorporeal shock wave
      lithotripsy.
AB  - OBJECTIVES: Previous publications have suggested that prolonged exposure to
      extracorporeal shock wave lithotripsy (ESWL) may lead to hearing damage and that
      hearing protection should be used. We sought to determine the auditory risk
      associated with ESWL in regard to patients and operating room personnel in a
      contemporary setting. METHODS: A single day study was performed during which 5
      patients were treated with ESWL via a Dornier Compact Delta lithotripter (Dornier
      MedTech America Inc, Kennesaw, Georgia). A sound level meter was used to evaluate
      the noise exposure to the patient, ESWL technician, anesthesia personnel, and the
      treating urologist. Multiple readings were taken at each station and during each
      treatment session while the patient was treated at maximum intensity level. These
      recordings were then averaged and referenced to published Occupational Safety and
      Health Administration (OSHA) standards. RESULTS: The greatest level of noise
      exposure was found to be at the head of the patient, with an average reading of
      89 decibels (dB). The readings at the lithotripter technician's station averaged
      84 dB. The anesthetist and urologist were exposed to average sound levels of 81
      and 79 dB, respectively. All readings at each evaluated station evidenced a level
      of exposure considered safe by OSHA standards, which permit 8 hours of exposure
      to 90 dB per day. CONCLUSIONS: Contemporary ESWL does not pose a significant
      auditory hazard to either the patient or operating room personnel by OSHA
      standards. Thus, in reference to these standards, hearing protection for the
      parties involved is not considered mandatory.

PMID- 18068445
TI  - Surgical resection provides excellent outcomes for patients with cystic clear
      cell renal cell carcinoma.
AB  - OBJECTIVES: Previous observations suggest that cystic clear cell renal cell
      carcinoma (RCC) is cured with surgical resection. However, long-term outcome data
      are lacking. We reviewed our experience with RCC and report on pathologic
      features and patient outcome associated with the cystic variant. METHODS: We
      identified 2431 patients treated with nephrectomy for unilateral, sporadic clear
      cell RCC between 1970 and 2002. A single urologic pathologist (J.C.C.) reviewed
      all of the microscopic slides without knowledge of patient outcome. Cystic clear
      cell RCC was characterized by numerous confluent cysts lined by clear cells, and
      containing nests of clear cells within the cyst walls. RESULTS: There were 85
      (3.5%) patients with cystic RCC. Among these patients, 22 died during follow-up,
      although no patient died of RCC. The median follow-up for the remaining 63
      patients was 5 years. The estimated cancer-specific survival rate at 5 years
      after surgery for patients with noncystic clear cell RCC was 70.6% compared with
      100% for patients with the cystic variant (P <0.001). This difference persisted
      even when comparing patients with cystic RCC to the subset with noncystic RCC who
      had pT1, pNx/pN0, and no clinical evidence of metastases (cM0). No patient with
      cystic clear cell RCC had extrarenal disease at time of nephrectomy with the
      exception of 1 patient who had perinephric fat invasion. CONCLUSIONS: Cystic RCC
      is a distinct pathologic entity and should be assessed routinely during
      pathologic evaluation. Furthermore, we present data supporting that cystic RCC
      patients should expect to be cured after surgical extirpation.

PMID- 18068447
TI  - Perioperative outcomes with laparoscopic radical cystectomy: "pure laparoscopic"
      and "open-assisted laparoscopic" approaches.
AB  - OBJECTIVES: Techniques for laparoscopic radical cystectomy are rapidly evolving.
      The entire procedure can be performed completely intracorporeally by pure
      laparoscopic techniques or by open-assisted laparoscopic techniques in which the
      urinary diversion is constructed extracorporeally by way of a minilaparotomy
      incision. We retrospectively evaluated the outcomes of these two techniques with
      a focus on perioperative outcomes and associated morbidity. METHODS: From
      December 1999 to March 2006, 54 patients underwent laparoscopic radical
      cystectomy for muscle invasive (n = 35) or high-risk non-muscle-invasive (n = 19)
      bladder cancer. The mean follow-up was 25 months (range, 1 to 66 months).
      RESULTS: Of the 54 patients, 17 underwent a pure laparoscopic (group 1, 8 conduit
      and 9 neobladder) and 37 underwent an open-assisted laparoscopic (group 2, 18
      conduit and 19 neobladder) procedure. No significant differences were noted
      between the groups in patient age, comorbidities, or pathologic stage of
      malignancy. Group 2 was superior with regard to operative time, blood loss,
      transfusion rate, time to oral intake, time to ambulation, and postoperative
      complications (P <0.05 for all comparisons). Anastomotic leak, bowel obstruction,
      or sepsis requiring reexploration developed in 5 patients (29%) in group 1 and 4
      patients (11%) in group 2. A "learning curve" was observed for both procedures,
      but it was particularly steep for the pure laparoscopic technique, and this
      approach was eventually abandoned. CONCLUSIONS: Laparoscopic radical cystectomy
      is associated with a learning curve, with morbidity largely resulting from the
      urinary diversion procedure. Our experience suggests that the open-assisted
      laparoscopic approach is technically more efficient and associated with a quicker
      recovery profile and decreased complication rates compared with the pure
      laparoscopic approach.

PMID- 18068448
TI  - Glomerulation observed during transurethral resection of the prostate for
      patients with lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia is a common finding but no predictor of clinical outcome.
AB  - OBJECTIVES: Although glomerulation in the bladder mucosa when the bladder is
      overdistended is a finding suggestive of interstitial cystitis (IC), it is
      sometimes observed at transurethral resection of the prostate (TURP) for patients
      with lower urinary tract symptoms suggestive of benign prostatic hyperplasia
      (LUTS/BPH). We prospectively investigated the incidence and clinical implications
      of glomerulation found at TURP. METHODS: From December 2003 to October 2005, 197
      patients aged 50 years or older who were considered to be appropriate candidates
      to undergo TURP for LUTS/BPH were investigated in this study. Just before
      beginning resection under spinal anesthesia, the bladder was filled to a water
      pressure of 80 cm and the capacity was measured. After evacuation of the fluid,
      careful inspection was conducted for glomerulation during refilling. Before TURP,
      and 3 and 12 months after TURP, the International Prostate Symptom Score and
      O'Leary-Sant IC Symptom and Problem Index were determined, and uroflowmetry and
      measurement of residual urine volume were performed. RESULTS: Glomerulation was
      observed in 40 of the 197 patients (20.3%). There was no difference in bladder
      capacity between the glomerulation and nonglomerulation groups, although the
      glomerulation group was younger with lighter resected weight and a higher
      baseline IC problem index than the nonglomerulation group. There were no
      differences in other parameters before, 3, and 12 months after TURP between the 2
      groups. CONCLUSIONS: Although glomerulation at TURP is a common finding, the
      clinical implications related to IC are unknown. Glomerulation itself may not be
      a predictor of the clinical outcome of TURP. Glomerulation observed during
      transurethral resection of the prostate for patients with lower urinary tract
      symptoms suggestive of benign prostatic hyperplasia is a common finding but no
      predictor of clinical outcome.

PMID- 18068449
TI  - Decreased efficiency of potassium-titanyl-phosphate laser photoselective
      vaporization prostatectomy with long-term 5 alpha-reductase inhibition therapy:
      is it true?
AB  - OBJECTIVES: 5 Alpha-reductase inhibitors (5ARIs) reduce angiogenesis in benign
      prostatic tissue. This has been postulated to affect the efficiency of the
      potassium-titanyl-phosphate (KTP) laser during photoselective vaporization
      prostatectomy (PVP), which has hemoglobin as its primary chromophore. We evaluate
      KTP laser PVP as treatment for benign prostatic hyperplasia (BPH) in patients on
      long-term 5ARIs. METHODS: We prospectively evaluated our initial 12 month KTP
      laser PVP experience with patients without or with 5ARIs. Transurethral PVP was
      performed with the use of an 80W KTP side-firing laser system. Voiding trials
      were performed 2 hours after surgery. International Prostate Symptom Score
      (IPSS), maximum flow rate (Qmax), and postvoid residual (PVR) were measured
      preoperatively and at 1, 4, 12, 24, and 52 weeks after surgery. RESULTS: One
      hundred sixty consecutive patients were identified, of which 117 were not on a
      5ARI and 43 were on either finasteride or dutasteride for at least 6 months. Mean
      prostate volumes were 72.8 +/- 49.5 cm3 and 70.8 +/- 49.1 cm3 (P = 0.39),
      respectively. There were no significant differences in the parameters of laser
      time (32.0 +/- 27.6 minutes and 37.0 +/- 36.2 minutes) and energy usage (97.4 +/-
      91.6 kJ and 103.3 +/- 86.0 kJ). All were outpatient procedures with the majority
      of patients catheter-free at discharge. All patients were able to discontinue
      their prostate medications after surgery. IPSS, Qmax, and PVR values showed
      significant improvement within each group, but the degree of improvement between
      the 2 groups did not show statistical significance. CONCLUSIONS: Our experience
      suggests that 5ARIs do not have a detrimental effect on the efficiency and
      efficacy of KTP laser PVP.

PMID- 18068450
TI  - Contemporary evaluation of the D'amico risk classification of prostate cancer.
AB  - OBJECTIVES: In 1998, D'Amico et al. suggested a model stratifying patients with
      prostate cancer into those with low, intermediate, or high-risk of biochemical
      recurrence after surgery according to the clinical TNM stage, biopsy Gleason
      score, and preoperative prostate-specific antigen level. We studied the
      performance and clinical relevance of this classification system over time, in
      the context of the stage migration seen in the contemporary era, using data from
      a high-volume, tertiary referral center. METHOD: From 1984 to 2005, 6652 men
      underwent radical prostatectomy at our institution for clinically localized
      prostate cancer (clinical Stage T1c-T2c) with follow-up information available and
      no neoadjuvant or adjuvant therapy before biochemical recurrence. Biochemical
      recurrence-free survival (BRFS) was estimated using the Kaplan-Meier method, and
      the BRFS rates between the D'Amico risk groups and by era were compared using the
      log-rank statistic. Finally, the distribution of patients among the three groups
      was compared over time. RESULTS: The 5-year BRFS rate was 84.6% overall and
      94.5%, 76.6%, and 54.6% for the low, intermediate, and high-risk groups,
      respectively (P <0.0001). In the contemporary era, a very small fraction (4.9%)
      of patients undergoing radical prostatectomy at our institution were in the high
      risk group, with most (67.7%) in the low-risk group (P <0.001). CONCLUSIONS: The
      D'Amico classification system continues to stratify men into risk groups with
      statistically significant differences in BRFS. However, the major shift in the
      distribution of patients among the three risk groups over time suggests that the
      clinical relevance of this classification scheme may be limited and diminishing
      in the contemporary era.

PMID- 18068451
TI  - Population-based case-control study of PSA and DRE screening on prostate cancer
      mortality.
AB  - OBJECTIVES: The efficacy of screening for prostate cancer (PCa) with digital
      rectal examination (DRE) and prostate-specific antigen (PSA) measurement has not
      been proved in randomized clinical trials. In an earlier case-control study, we
      found that DRE might reduce PCa mortality. The present case-control study
      assessed the association between PSA and DRE testing and PCa mortality. METHODS:
      The case subjects included 74 Olmsted County residents who had died from 1992 to
      2005 with PCa as the underlying cause of death. From 1 to 3 community control
      subjects (alive at time of case subject's death) were matched to each case
      subject. The medical records were reviewed to identify DREs and PSA
      determinations performed 0 to 5 years before the date the case was diagnosed
      (index date). Tests performed in the absence of symptoms were considered to be
      "screening tests." Conditional logistic regression analysis was used to estimate
      the odds ratios and 95% confidence intervals for the association of screening
      (defined in multiple ways) and PCa mortality. RESULTS: From 1 to 5 years before
      the index date, control subjects were more likely than case subjects to have
      undergone a previous screening PSA test or DRE (81.3% versus 60.8%, P = 0.0005).
      The unadjusted odds ratio associated with a previous screening PSA test or DRE
      was 0.34 (95% confidence interval 0.18 to 0.63), and the odds ratio adjusted for
      potential confounders was 0.35 (95% confidence interval 0.17 to 0.71). PSA
      testing was frequently done in conjunction with DRE, making evaluation of the
      individual effects difficult. CONCLUSIONS: The results of this case-control study
      suggest a potential benefit of screening by PSA testing and/or DRE on PCa
      mortality.

PMID- 18068452
TI  - Efficacy of artificial urinary sphincter implantation after failed bone-anchored
      male sling for postprostatectomy incontinence.
AB  - OBJECTIVES: To evaluate the feasibility and efficacy of artificial urinary
      sphincter placement after failed bone-anchored male sling for postprostatectomy
      stress urinary incontinence. METHODS: Eleven patients with postprostatectomy
      stress urinary incontinence who failed bone-anchored male sling underwent
      artificial urinary sphincter placement. All patients were evaluated before and
      after artificial urinary sphincter placement with a history and physical
      examination, pad score, and the incontinence section of the University of
      California, Los Angeles (UCLA)/RAND prostate cancer index (total score possible =
      26). Urodynamic evaluation was performed before sphincter placement. RESULTS: The
      average age in our study population was 70 years (range, 51 to 80 years). The
      mean follow-up after artificial urinary sphincter placement was 14.2 months
      (range, 3 to 20 months). Incontinence was defined as mild (1 to 2 pads), moderate
      (3 to 5 pads), or severe (more then 5 pads). After sling placement, cure was
      defined as no pad use, failure as same pad usage, and improvement as fewer pads
      used. The severity of incontinence before artificial urinary sphincter placement
      was mild, moderate, and severe in 3, 1, and 7 patients, respectively. After
      artificial urinary sphincter placement the severity of incontinence was cured,
      mild, and moderate in 8, 2, and 0, respectively. One patient required artificial
      urinary sphincter removal because of infection. Mean UCLA/RAND scores increased
      from 10.8 to 19.7. Patient satisfaction after artificial urinary sphincter
      placement was 74.5%. No intraoperative complications or urethral injuries
      occurred. CONCLUSIONS: Artificial urinary sphincter placement after failed bone
      anchored male sling is technically feasible and does not affect the short-term
      efficacy of the artificial sphincter.

PMID- 18068453
TI  - Improved stage and grade-specific progression-free survival rates after radical
      prostatectomy in the PSA era.
AB  - OBJECTIVES: Since the initiation of prostate-specific antigen (PSA) screening,
      the progression-free survival (PFS) rates after radical prostatectomy have
      markedly improved. However, few studies have evaluated whether PFS has improved
      for stage and grade-matched patients. Our objective was to examine differences in
      PFS after radical prostatectomy between the pre-PSA era (before 1992) and the PSA
      era, controlling for tumor stage and grade. METHODS: From 1983 to 2003, 3456 men
      underwent radical prostatectomy by one surgeon. The 10-year PFS rates were
      calculated for each era and stratified by pathologic tumor stage and grade.
      Kaplan-Meier curves were generated to show biochemical PFS over time. RESULTS:
      The proportion of patients with pathologically organ-confined disease increased
      from 64% to 69%, consistent with stage migration. The PFS rate in the PSA era was
      87%, 63%, 58%, and 31% versus 71%, 63%, 47%, and 19% in the pre-PSA era for Stage
      pT2R0, pT3R0, pT2-T3R1, and pT3c/N1 disease, respectively. The PFS rate
      stratified by Gleason grade in the PSA era was 84%, 63%, and 37% versus 66%, 49%,
      and 32% in the pre-PSA era for Gleason grade less than 7, 7, and 8 to 10,
      respectively. The 10-year PFS rate for organ-confined disease improved from 70%
      in the pre-PSA era to 86% in the PSA era. CONCLUSIONS: Patients treated with
      radical prostatectomy in the PSA era have improved survival outcomes when
      controlling for pathologic stage and grade. This is likely attributed to the
      earlier detection of cancer through PSA screening, better identification of
      patients amenable to curative therapy, and the effects of lead-time bias.

PMID- 18068454
TI  - Inguinal hernias in men undergoing open radical retropubic prostatectomy.
AB  - OBJECTIVES: To determine the incidence of inguinal hernias in men undergoing open
      radical retropubic prostatectomy (RRP). METHODS: The incidence of preoperative
      and postprostatectomy inguinal hernias were determined by a retrospective chart
      review and questionnaire survey of 1130 consecutive men who underwent open RRP by
      a single surgeon from October 2000 to October 2005. A preoperative inguinal
      hernia was diagnosed by the physical examination or abdominal computed tomography
      findings. The incidence of new postoperative hernias was ascertained by the
      patients' responses to a survey indicating the development of a new groin bulge
      or hernia. RESULTS: Of the 1130 patients, 146 (13%) had a preoperative inguinal
      hernia. Increasing age and lower body mass index were significantly associated
      with the detection of a preoperative inguinal hernia. The sensitivity of
      detecting an inguinal hernia by physical examination and routine abdominal
      computed tomography preoperatively was 96.3% and 42.5%, respectively. Also, 8% of
      men developed a new hernia. CONCLUSIONS: Although abdominal computed tomography
      can identify inguinal hernias in men undergoing open RRP, the test's sensitivity
      is inferior to that of a simple physical examination. All candidates for open RRP
      should undergo a careful physical examination to identify asymptomatic inguinal
      hernias. Our findings suggest that the previously reported high incidence of
      symptomatic inguinal hernias that developed after open RRP can be explained by a
      failure to diagnose preexisting inguinal hernias and the development of new
      hernias.

PMID- 18068455
TI  - Prognostic significance of location of positive margins in radical prostatectomy
      specimens.
AB  - OBJECTIVES: Cancer at the resection margin is associated with an increased risk
      of biochemical recurrence after radical prostatectomy (RP) even after adjusting
      for other known clinical and pathologic risk factors. In this study, we assessed
      the prognostic significance of sites of positive surgical margins (+SMs) in RP
      specimens. METHODS: We reviewed the data from 2442 patients with clinical Stage
      T1-T3 prostate cancer treated with RP from 1983 to 2004 who had had tumor maps
      generated from whole mount sections. The site of +SMs was assigned to six
      different areas (apex, bladder neck, seminal vesicle, anterior, posterolateral,
      and posterior). RESULTS: Of the 2442 patients, 201 (8.2%) had a +SM at a single
      site and 74 (3.0%) had a +SM at multiple sites in the RP specimen. The
      posterolateral and apex sections were the most commonly involved sites for a +SM.
      Those with a +SM had a greater risk of biochemical recurrence than those with
      negative surgical margins (hazard ratio 1.39, 95% confidence interval 1.004 to
      1.92; P = 0.047). We found that a +SM at the posterolateral site was
      significantly associated with an increased risk of biochemical recurrence (hazard
      ratio 2.80 for +SMs versus negative SMs at the posterolateral region; 95%
      confidence interval 1.76 to 4.44). CONCLUSIONS: The effect on biochemical
      recurrence was influenced by the site of the +SM, with a posterolateral location
      having the most significant effect on prognosis. This heterogeneity of margin
      status has implications for predictive modeling, as well as the recommendation
      for adjuvant radiotherapy.

PMID- 18068456
TI  - The RoboConsultant: telementoring and remote presence in the operating room
      during minimally invasive urologic surgeries using a novel mobile robotic
      interface.
AB  - OBJECTIVES: Remote presence is the ability of an individual to project himself
      from one location to another to see, hear, roam, talk, and interact just as if
      that individual were actually there. The objective of this study was to evaluate
      the efficacy and functionality of a novel mobile robotic telementoring system
      controlled by a portable laptop control station linked via broadband Internet
      connection. METHODS: RoboConsultant (RemotePresence-7; InTouch Health, Sunnyvale,
      CA) was employed for the purpose of intraoperative telementoring and consultation
      during five laparoscopic and endoscopic urologic procedures. Robot functionality
      including navigation, zoom capability, examination of external and internal
      endoscopic camera views, and telestration were evaluated. The robot was
      controlled by a senior surgeon from various locations ranging from an adjacent
      operating room to an affiliated hospital 5 miles away. RESULTS: The
      RoboConsultant performed without connection failure or interruption in each case,
      allowing the consulting surgeon to immerse himself and navigate within the
      operating room environment and provide effective communication, mentoring,
      telestration, and consultation. CONCLUSIONS: RoboConsultant provided clear, real
      time, and effective telementoring and telestration and allowed the operator to
      experience remote presence in the operating room environment as a surgical
      consultant. The portable laptop control station and wireless connectivity allowed
      the consultant to be mobile and interact with the operating room team from
      virtually any location. In the future, the remote presence provided by the
      RoboConsultant may provide useful and effective intraoperative consultation by
      expert surgeons located in remote sites.

PMID- 18068457
TI  - Squamous cell carcinoma antigen correlates with tumor burden but lacks prognostic
      potential for occult lymph node metastases in penile cancer.
AB  - OBJECTIVES: In penile cancer, radical groin dissection is the reference standard
      for lymph node staging, but it is associated with high morbidity. Prognostic
      markers for lymphatic spread would be helpful to select patients for a
      surveillance program. Squamous cell carcinoma (SCC) antigen is a well-known
      marker for various carcinomas. Our aim was to evaluate the value of the SCC
      antigen in terms of lymph node staging and treatment control. METHODS: From 1994
      to 2004, the serum levels of SCC antigen were analyzed in 54 men with penile
      carcinoma at different disease stages. The SCC antigen values were compared in
      patients without evidence of tumor, with a primary tumor only, with nodal
      metastases, and with progressive metastatic disease. In 13 patients, repeated SCC
      antigen measurements correlated with the treatment effects. RESULTS: Once lymph
      node metastases occurred, a trend was found toward increased SCC antigen levels
      and at the stage of organ metastases, the SCC antigen levels had risen
      significantly (P <0.01). In cases of repeated measurements, a correlation was
      found between SCC antigen values and treatment effect. A response to treatment
      occurred, even if the values were within normal limits. CONCLUSIONS: The SCC
      antigen levels seemed to correlate with tumor burden in patients with penile
      carcinoma. However, it is of limited value in the primary prediction of occult
      lymph node metastases because the SCC antigen levels increased significantly only
      after massive lymph node involvement or metastatic disease has occurred. However,
      the SCC antigen could be used as a marker for treatment control in penile
      carcinoma.

PMID- 18068458
TI  - Primary congenital bladder diverticula in children.
AB  - OBJECTIVES: To present the symptoms, treatment, evolution, and pathologic
      findings of primary (nonobstructive) diverticula in childhood. Primary
      (nonobstructive) diverticula are not frequent in childhood. Bladder diverticula
      have classically been defined as "hernias of the mucosa through muscular fibers
      of the bladder wall." METHODS: From September 1985 through September 2005, we
      treated 11 children categorized has having primary congenital bladder
      diverticula. At diagnosis, their ages ranged between 7 months and 9 years (mean
      4.6 years). Ten were boys and one was a girl. The main reason for consultation
      was febrile urinary infection (n = 5), recurrent urinary infections (n = 3),
      enuretic syndrome (n = 1), gross hematuria (n = 1), and pain in the right iliac
      fossa (n = 1). One child had Ehlers-Danlos syndrome. All the diverticula were
      larger than 2 cm in diameter. Of the 11 children, 10 underwent surgery. Clinical
      observation was chosen for the 9-month-old infant. RESULTS: All 10 operated
      children had developed favorably at a follow-up of 2 to 20 years (mean 9.3). The
      9-month-old child continued under observation for 5 years. We observed no
      diverticulum recurrence and no postoperative vesicoureteral reflux in the
      reimplanted children. Pathologic examination was performed of the excised
      diverticula in 7 cases, and muscular fibers were found in all of them; however,
      most of the fibers were very fine, particularly at the dome of the diverticulum.
      CONCLUSIONS: The results of our study have shown that urinary tract infection is
      the most common symptom of bladder diverticula. Surgical treatment provided good
      results, without any recurrence or morbidity. The bladder diverticula were lined
      with fine muscular fibers.

PMID- 18068459
TI  - Longitudinal study of semen quality in adolescents with varicocele: to treat or
      not?
AB  - OBJECTIVES: To assess the role of varicocelectomy in pediatric patients through a
      careful semen analysis. METHODS: A total of 214 patients with grade 2 and 3 left
      idiopathic varicocele were enrolled. Of these 214 patients, 106 (group 1) were
      treated surgically for testicular hypotrophy, 54 (group 2) were treated
      surgically with a normal testis, and 54 with a normal testis (group 3) were
      observed with follow-up visits every 6 months. The spermiogram results for each
      group were divided into two subgroups: normal, if they met the evaluation
      criteria and abnormal in the remaining cases. RESULTS: The spermiogram analysis
      for groups 1 and 2 showed no statistically significant difference in terms of
      normal and abnormal spermiogram findings (P >0.01). Even though the patients
      included in group 3 had reported no testicular hypotrophy or pain, the
      qualitative semen analysis showed the same trend observed in patients affected by
      varicocele, but the difference was not statistically significant in the variables
      considered for the other groups (P >0.01). Preservation of the testicular artery
      in patients with hypotrophy was associated with better results in terms of semen
      quality. CONCLUSIONS: Testicular hypotrophy remains the most objective indication
      for surgical treatment of varicocele, and preservation of the testicular artery
      gives better results in terms of semen quality only in patients affected by
      testicular hypotrophy.

PMID- 18068460
TI  - Intracorporeal one-hand tie technique for renal pedicle ligation during hand
      assisted retroperitoneoscopic nephrectomy.
AB  - We devised an intracorporeal one-hand tie technique to ligate the renal pedicle
      during hand-assisted retroperitoneoscopic nephrectomy.

PMID- 18068461
TI  - Pedicled anterolateral thigh flap for reconstruction after radical groin
      dissection.
AB  - INTRODUCTION: Inguinal lymphadenectomy is performed for the treatment of nodal
      metastases from squamous cell carcinoma of the penis and other tumors of the
      trunk and lower extremity. Malignant skin infiltration requires wide resection,
      producing a defect requiring complex soft-tissue reconstruction. We have used a
      pedicled anterolateral thigh flap as our first-choice flap for these cases. We
      report a prospective series of cases using this recently described flap for
      reconstruction of groin defects after radical groin dissection. TECHNICAL
      CONSIDERATIONS: From May 2001, 6 patients with locally advanced inguinal disease
      underwent wide skin excision and en bloc nodal resection with immediate
      reconstruction using a pedicled anterolateral thigh flap. Data were collected
      prospectively, and the data of 4 of 6 patients were reviewed at 6 months
      postoperatively. No flap losses occurred. Complete healing was achieved in all
      patients. The mean hospital stay was 18 days. The median time to complete healing
      was 33.5 days. The complications were seroma leading to flap congestion, wound
      dehiscence, wound infection, and delayed healing. The donor sites were either
      closed primarily or split skin grafted. CONCLUSIONS: Reconstruction using a
      pedicled anterolateral thigh flap in patients with advanced inguinal nodal
      disease is a useful adjunct in selected patients. We present our indications for
      the procedure, our rational for the choosing this technique over other methods of
      reconstruction, and the difficulties we experienced.

PMID- 18068462
TI  - Anatomic excision of anterior prostatic fat at radical prostatectomy:
      implications for pathologic upstaging.
AB  - INTRODUCTION: After exposure of the retropubic space, the surgeon commonly
      dissects the fat overlying the prostate and usually discards it. We have
      previously described the importance of dissecting this fat to completely
      visualize the dorsal venous complex (DVC) and prostatic apex. In this study, we
      describe a technique to dissect and remove the anterior prostatic fat pad (APF)
      and its anatomic and pathologic significance. TECHNICAL CONSIDERATIONS: After the
      retropubic space was prepared, we dissected the fat overlying the puboprostatic
      ligaments and the DVC to fully expose these structures. The superficial branch of
      the DVC was then transected, and the fat was dissected cephalad to the junction
      with the bladder. The fat was then further dissected laterally toward the lateral
      pelvic sidewall. Video analysis of the lateral dissection of the fat revealed a
      direct link to the obturator lymph node chain, where it was transected.
      Pathologic analysis demonstrated that 30 (14.7%) of 204 patients had one or more
      APF lymph nodes, of which four were positive for metastatic prostate cancer. The
      cancer of 3 of these 4 patients was upstaged as a result of the detection of
      these positive nodes. CONCLUSIONS: The dissection of the APF facilitates
      visualization of the apex and bladder neck. Anatomically, we have demonstrated
      that the APF contains lymph nodes approximately 15% of the time that are in
      communication with the obturator lymph node chain and DVC. We found that removal
      of the APF and its pathologic analysis can result in pathologic upstaging.

PMID- 18068463
TI  - Recurrent mass after laparoscopic partial nephrectomy.

PMID- 18068464
TI  - Calcification of tunica vaginalis in a case of longstanding hydrocele.

PMID- 18068465
TI  - Laparoscopic nephrectomy, ex vivo partial nephrectomy followed by allograft renal
      transplantation.
AB  - A shortage of available kidneys exists. Forty percent of patients with end stage
      renal disease wait more than 2 years for renal transplant. We report a case of a
      22-year-old man who underwent laparoscopic radical nephrectomy for a 2-cm central
      renal mass. Ex vivo partial nephrectomy and renorraphy were performed. The
      reconstructed kidney was allotransplanted to a 62-year-old man with end stage
      renal disease. The recipient has excellent graft function. Imaging shows no
      evidence of recurrence or metastasis at 2 years' follow-up. Incidence and
      management of de novo renal cell carcinoma in renal allografts are reviewed.

PMID- 18068466
TI  - Mechanical failure with malleable penile prosthesis.
AB  - Mechanical failure with a malleable penile prosthesis is very rare, and no
      mechanical failure has been reported with the AMS 650 malleable penile
      prosthesis. A 67-year-old man, using the AMS 650 malleable penile prosthesis
      without a problem since 1999, presented with right penile deformity and
      difficulty in sexual intercourse for the preceding 2 months. Physical examination
      showed dislocation of the right rod of the penile prosthesis, and surgical
      exploration revealed a fracture in the rod. The malfunctioning right penile
      prosthesis was removed, and a new AMS 650 malleable penile prosthesis was
      implanted. The patient did not have any problem at 1-year follow-up.

PMID- 18068467
TI  - Histologically pure stage I seminoma with an elevated beta-hCG of 4497 IU/l.
AB  - Approximately 30% of patients with pure seminoma of the testis have mild
      elevation of human chorionic gonadotropin (hCG) due to the presence of
      syncytiotrophoblastic giant cells. Levels are usually less than 500 IU/L;
      however, the occurrence of higher levels is rare. We report a case of a man with
      a stage I histologically pure seminoma, copious syncytiotrophoblast cells, and a
      serum beta human chorionic gonadotropin (beta-hCG) of 4497 IU/L. To our knowledge
      this is the third highest value of beta-hCG reported with a stage I pure
      seminoma. The patient underwent an orchiectomy and chemotherapy. His beta-hCG
      level was undetectable by postoperative day 13, and he remains disease free at 30
      months.

PMID- 18068468
TI  - Isolated prostate cancer recurrence presenting as pelvic mass nine years after
      radical retropubic prostatectomy.
AB  - Pelvic seeding from radical retropubic prostatectomy for adenocarcinoma of the
      prostate is uncommon. We describe a patient who presented with a prostate
      specific antigen recurrence and was found to have a solitary metastasis adjacent
      to his pubic bone 9 years after radical prostatectomy. Computed tomography
      scanning followed by surgery documented the pelvic recurrence.

PMID- 18068469
TI  - Solitary schwannoma of the glans penis.
AB  - Schwannomas of the penis are extremely rare. A 69-year-old man presented with a
      circumscribed asymptomatic tumor on the dorsum of the glans penis.
      Histopathologic examination of the surgical specimen showed a benign schwannoma.

PMID- 18068470
TI  - A rare case of classic testicular seminoma in an 86-year-old shows similar
      proliferation rate as in younger men.
AB  - We present a rare case of classic seminoma in an 86-year-old man. Combined
      mitotic count, the presence or absence of intravascular invasion, and the
      expression of PCNA, Ki67, and p53 were compared between this octogenarian and the
      tumors of four randomly selected standard younger men. These histologic features
      were chosen to compare the potential biologic activity of these tumors. The
      phenotype of classic seminomas in octogenarians seems to be the same as in
      younger men, and treatment paradigms should remain unchanged.

PMID- 18068471
TI  - Rare combination of unilateral renal agenesis, congenital obstructive posterior
      urethral membrane, and enlarged prostatic utricle, with absence of
      hydroureteronephrosis.
AB  - The existence of congenital obstructive posterior urethral membrane (COPUM),
      extending proximally from the verumontanum toward the bladder neck, has been
      widely debated. Although COPUM often leads to chronic renal disease, a milder
      degree of obstruction and protective pressure pop-off mechanisms have been
      reported. We present a male infant with a rare combination of unilateral renal
      agenesis, COPUM proximally from the verumontanum to the bladder neck, and
      enlarged prostatic utricle. The posterior urethra was dilated, without bladder
      abnormalities or hydroureteronephrosis, indicating milder obstruction. Moreover,
      the enlarged prostatic utricle could contribute in the urinary tract protection,
      serving as an uncommon pressure pop-off mechanism.

PMID- 18068472
TI  - Primary non-Hodgkin's B-cell lymphoma of the male urethra presenting as stricture
      disease.
AB  - Primary urethral lymphoma is exceedingly rare. There are only three cases
      reported involving the male urethra, with one in an immunocompromised man. We
      report a case of primary B-cell lymphoma presenting as complex urethral stricture
      disease.

PMID- 18068473
TI  - Anterior urethral valve in an adolescent with nocturnal enuresis.
AB  - The anterior urethral valve (AUV) is a rare congenital urethral anomaly that can
      lead to variable urinary tract symptoms. We report on a 13-year-old boy with AUV
      who was referred from a primary care physician for nocturnal enuresis. AUV was
      disclosed by videourodynamic study and confirmed by simultaneous retrograde
      cystourethroscopy and antegrade urethroscopy. The AUV was ablated by
      neodymium:yttrium-aluminum-garnet contact laser at the 5-o'clock and 7-o'clock
      directions. A postoperative videourodynamic study depicted a patent urethra, a
      good maximal flow rate, and improved bladder capacity. His nocturnal enuresis had
      completely subsided at a follow-up period of longer than 24 months.

PMID- 18068474
TI  - Large mixed epithelial and stromal tumor of the kidney masquerading as metastatic
      renal cell carcinoma.
AB  - We report the case of a 39-year-old woman with a large right renal mass 20 cm in
      size with heterogeneous solid and cystic components as well as concurrent liver
      lesions suspicious for metastatic renal cell carcinoma. Surgical extirpation of
      the renal mass and liver lesions was performed laparoscopically with the
      pathological analysis revealing a rare renal neoplasm--mixed epithelial and
      stromal tumor of the kidney--and adenomas of the liver.

PMID- 18068475
TI  - Urethral diverticulum after endoscopic urethrotomy: case report.
AB  - Diverticula of the male penile urethra are rare clinical entities. Urethral
      diverticula in males may be associated with trauma, infection, impacted calculi
      or stricture disease. Herein, we present an unusual case of a 57-year-old man
      with erectile dysfunction and a symptomatic urethral diverticulum after
      endoscopic urethrotomy for a pendulous urethral stricture. One year after
      surgical repair involving urethral stricture excision, end-to-end primary
      urethroplasty, and closure of the diverticular neck, the patient is voiding well
      but has persistent erectile dysfunction unresponsive to phosphodiesterase-5
      inhibitors.

PMID- 18068476
TI  - Open prostatolithotomy for the management of giant prostatic calculi.
AB  - Giant prostatic calculi are very rare. We present the case of a 45-year-old man
      with multiple prostatic urethral calculi that replaced the entire gland. He
      underwent an open "prostatolithotomy," a novel method of stone removal akin to a
      simple retropubic prostatectomy. Eight stones weighing a total of 59 g were
      removed from the prostate. For certain patients, adjunctive vesical neck revision
      and deliberate drainage of the prostatic fossa may be beneficial in addition to
      stone extraction.

PMID- 18068477
TI  - Use of a sulfated chitosan derivative to reduce bladder inflammation in the rat.
AB  - OBJECTIVES: Interstitial cystitis is a chronic, debilitating disease of the
      bladder. Treatments using intravesicular inoculation of long-chain polysaccharide
      formulations, such as hyaluronic acid or anti-inflammatory agents, have been used
      to some effect. The objective of this study was to test a long-chain
      polysaccharide derivative of chitosan as a vehicle for delivery of the anti
      inflammatory agent 5-aminosalicylic acid (5-ASA) for treatment of inflammation in
      the bladder. METHODS: Bladder inflammation was induced in rats by intravesicular
      inoculation of protamine sulfate and lipopolysaccharide. Groups of rats were
      randomly assigned to the treated or control groups, which received either the
      treatment agents or saline 24 hours after induction. The animals were killed 5
      days after inoculation, and the bladders harvested for histologic examination of
      inflammation by a blinded observer. Four parameters of inflammation were measured
      using a 6-point scale. In another experiment, urinary frequency was measured 4
      days after inoculation. RESULTS: The most potent treatment agent was 3% N
      sulphonato-N,O-carboxymethylchitosan plus 5-ASA, with a mean reduction in
      inflammation, as measured by histologic examination, of up to 75%. This level of
      reduction was significantly greater than that seen by treatment with the
      commercially available product Cystistat. In a separate experiment, 3% N
      sulphonato-N,O-carboxymethylchitosan plus 5-ASA ameliorated the increase in
      urinary frequency seen in induced, untreated animals. CONCLUSIONS: The
      combination of 3% N-sulphonato-N,O-carboxymethylchitosan and 5-ASA reduced
      bladder inflammation as measured by histologic examination and by the lower
      urinary frequency.

PMID- 18068478
TI  - Localization of increased insulin-like growth factor binding protein-3 in
      diabetic rat penis: implications for erectile dysfunction.
AB  - OBJECTIVES: Diabetes-induced erectile dysfunction (ED) is assumed to result from
      neurovascular abnormalities. However, the entire picture of the molecular
      mechanisms underlying ED has not yet been clarified. To elucidate the possible
      elements involved in ED in diabetes mellitus, we performed broad-scale gene
      expression profiling using cDNA array in the penis of streptozotocin-induced
      diabetic rats. METHODS: Northern blot analysis was performed to examine the
      course of the mRNA expression encoded by the identified gene.
      Immunohistochemistry was performed to identify the cellular localization of the
      encoded protein. RESULTS: Of the genes investigated, the expression level of
      insulin-like growth factor binding protein 3 (IGFBP-3) was greatly increased at
      12 weeks after streptozotocin treatment. The levels of ErbB3 epidermal growth
      factor receptor-related proto-oncogene, G1/S-specific cyclin D2, hepatic neutral
      cholesteryl ester hydrolase precursor, UDP-galactose ceramide
      galactosyltransferase, and serine protease RNK-Met-1 were markedly decreased.
      Increased levels of IGFBP-3 mRNA were demonstrated as early as 2 weeks after
      induction of hyperglycemia. Increased IGFBP-3 protein was localized to the
      epithelium of the urethra, penile endothelium, and smooth muscle in the corpus
      cavernosum. Significant depletion of the smooth muscle density relative to the
      connective tissue was first observed in the penis of the 8-week diabetic rats,
      and a significant reduction in the intracavernous pressure was demonstrated only
      at 12 weeks after the induction of hyperglycemia. CONCLUSIONS: These results
      suggest that the increased expression of IGFBP-3 during hyperglycemia might play
      an important role in the development of ED.

PMID- 18068479
TI  - Comparison of the histologic accuracy of needle biopsy before and after renal
      cryoablation: laboratory and initial clinical experience.
AB  - OBJECTIVES: To minimize the risk of needle biopsy, including tumor seeding and
      hemorrhage, we examined the feasibility of needle biopsy after renal
      cryoablation. METHODS: Four cryolesions were created bilaterally on normal
      porcine renal tissue with an 8-minute double-freeze cycle using a single 17-gauge
      cryoprobe. Biopsies were obtained with a 16G biopsy needle before and after
      cryoablation under direct vision. Each biopsy specimen was evaluated for the
      number of glomeruli and arterioles. We used a two-sample t-test to analyze the
      data. Subsequently, 10 patients with small renal masses underwent laparoscopic
      cryoablation using a standard double freeze-thaw cycle. We used an 18G biopsy
      needle to sample the renal mass with a single core taken before and after
      cryoablation. A blinded pathologist evaluated the specimens for the histologic
      accuracy of the two sampling techniques. We used chi-square statistic to
      determine an association between the diagnostic quality of the core specimens.
      RESULTS: Two hundred biopsies were obtained from porcine renal tissue. The
      average number of glomeruli for the pre- and postcryoablation sample was 9.6, and
      7.8, respectively (P = 0.04). The average number of arterioles for the pre- and
      postcryoablation group was 2.3 and 1.9, respectively (P = 0.04). During clinical
      application, seven of 10 precryoablation and seven of 10 postcryoablation
      biopsies were diagnostic (P = 0.639). Histopathology was established in all 10
      cases. There was no significant bleeding from any needle biopsy. CONCLUSIONS: The
      porcine model established the feasibility of histologic diagnosis after
      cryoablation. Our preliminary clinical experience demonstrates that
      postcryoablation biopsy has similar diagnostic yields to precryoablation biopsy.

PMID- 18068480
TI  - Validation of World Health Organization/International Society of Urologic
      Pathology 2004 classification schema for bladder urothelial carcinomas using
      quantitative nuclear morphometry: identification of predictive features using
      bootstrap method.
AB  - OBJECTIVES: Despite the introduction of the new World Health Organization 2004
      grading classification, the grading of urothelial carcinoma remains difficult and
      subjective. The aim of this study was to evaluate the role of computer-assisted
      image morphometric analysis as a tool to improve the objectivity of histologic
      grading of urothelial carcinoma. METHODS: A total of 75 urinary bladder biopsies
      from a cohort of patients with a first-time diagnosis of urothelial carcinoma
      representing low-grade (n = 19) and high-grade (n = 56) urothelial carcinoma were
      evaluated. Quantitative nuclear morphometry was performed on these biopsies using
      approximately 80 to 100 cells per case. A total of 17 nuclear morphometry
      features were extracted, and a bootstrap-based predictor selection using stepwise
      logistic regression analysis was performed. Subsequently, a validation was
      performed using the five top features from the logistic regression analyses by
      implementing a nonparametric discriminant analysis to identify the most
      discriminative features that predicted for high-grade cases. RESULTS: The
      bootstrap technique included nuclear pleomorphism as the most frequently selected
      predictor of high-grade urothelial carcinoma (in 213 of 500 replicates).
      Validation using the top five features in the logistic regression analysis method
      (pleomorphism, configuration run length, DNA mass, feret-Y, and age) using
      discriminant analysis gave a resubstitution error of 4%, indicating the
      usefulness of the selected predictors. CONCLUSIONS: The present study is the
      first to provide a morphometric validation of the World Health Organization 2004
      system for pathologic grading of bladder cancer. Furthermore, quantitative
      nuclear morphometry could aid in the objective grading of urinary bladder
      biopsies. This information might aid the treating physicians in better risk
      stratification of patients with urothelial carcinoma.

PMID- 18068481
TI  - Use of a novel ex-vivo model to compare the hemostatic properties of
      plasmakinetic resection, transurethral vaporization resection and conventional
      transurethral resection of the prostate.
AB  - OBJECTIVES: To compare the hemostatic properties of transurethral plasmakinetic
      resection of the prostate (PKRP), transurethral vaporization resection of the
      prostate (TUVRP) and transurethral resection of the prostate (TURP) ex vivo, as
      perioperative bleeding is still regarded as one of major complications of
      transurethral prostatectomy. METHODS: The modified model of isolated normal
      saline (NS)-perfused porcine kidney was used to determine the hemostatic efficacy
      of PKRP, TUVRP, and TURP. The loss of normal saline was semiquantitatively
      measured in relation to tissue ablation for the 3 techniques and specimens were
      evaluated histologically. RESULTS: The median values of NS loss rate of PKRP,
      TUVRP, and TURP were 4.02, 3.74, and 6.51 mL/min, respectively. The NS loss rate
      of TUVRP and PKRP were obviously lower than that of TURP (P <0.05). The
      difference between the NS loss rate of PKRP and TUVRP was not significant (P
      >0.05). The median values of depths of the coagulation zones of PKRP, TUVRP, and
      TURP were 217, 292, and 140 microm, respectively. Coagulation depth with TURP was
      significantly smaller than that with TUVRP and PKRP (P <0.05). Coagulation depth
      with PKRP was also smaller than that with TUVRP (P <0.05). CONCLUSIONS: PKRP is
      comparable with TUVRP in hemostasis and both of them could cause significantly
      less perioperative bleeding than TURP.

PMID- 18068483
TI  - The filaggrin story: novel insights into skin-barrier function and disease.
AB  - Recent reports have uncovered the key role of the protein filaggrin in
      maintaining an effective skin barrier against the external environment. Loss-of
      function mutations in the profilaggrin gene (FLG) are common and are present in
      up to 10% of the population. These mutations are the cause of the semi-dominant
      skin-scaling disorder ichthyosis vulgaris and are a major risk factor for the
      development of atopic dermatitis. The discovery of these mutations also provides
      new data concerning the genetics of atopic asthma as well as intriguing insight
      into disease mechanisms of systemic allergies involving antigen exposure in skin
      with defective barrier function. Collectively, these novel findings have
      significant implications for the classification and future clinical management of
      patients with atopic and allergic diseases.

PMID- 18068484
TI  - Preserving skeletal wellness throughout the continuum of care in patients with
      cancer. Introduction.

PMID- 18068482
TI  - Pleiotropic effects of statin therapy: molecular mechanisms and clinical results.
AB  - Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase, which is required for cholesterol biosynthesis, and are beneficial in
      the primary and secondary prevention of cardiovascular disease. Most of the
      benefits of statin therapy are owing to the lowering of serum cholesterol levels.
      However, by inhibiting HMG-CoA reductase, statins can also inhibit the synthesis
      of isoprenoids, which are important lipid attachments for intracellular signaling
      molecules, such as Rho, Rac and Cdc42. Therefore, it is possible that statins
      might exert cholesterol-independent or 'pleiotropic' effects through direct
      inhibition of these small GTP-binding proteins. Recent studies have shown that
      statins might have important roles in diseases that are not mediated by
      cholesterol. Here, we review data from recent clinical trials that support the
      concept of statin pleiotropy and provide a rationale for their clinical
      importance.

PMID- 18068485
TI  - Emerging strategies in bone health management for the adjuvant patient.
AB  - Cancer patients suffering from bone metastases are at increased risk for skeletal
      complications, which contribute to increased morbidity and negatively affect
      patient quality of life. Therefore, there has been great interest in the
      development of clinical therapies to prevent bone metastases. Bisphosphonates are
      currently used for the treatment of bone metastases secondary to solid tumors,
      including tumors of the breast, prostate, and lung. Current evidence indicates
      that nitrogen-containing bisphosphonates may have antitumor potential.
      Preclinical studies using in vitro and in vivo cancer models have shown that
      zoledronic acid, a third-generation bisphosphonate, can inhibit angiogenesis,
      invasion and adhesion of tumor cells, and overall tumor progression. Furthermore,
      pilot clinical studies suggest that zoledronic acid can prevent bone metastases,
      and larger clinical trials are under way (AZURE, NSABP-B-34, S0307, ZEUS, G2419)
      to examine the use of bisphosphonates for prevention of bone metastases in
      adjuvant therapy settings. Biochemical markers of bone turnover and tumor markers
      are being characterized and may provide useful tools to identify high-risk
      patients who may especially benefit from bisphosphonate therapy.

PMID- 18068486
TI  - Clinical benefits and considerations of bisphosphonate treatment in metastatic
      bone disease.
AB  - Patients with metastatic bone disease are at risk for developing skeletal-related
      events that can negatively influence quality of life, contributing to loss of
      autonomy and functional capabilities. Bisphosphonates have become an important
      component in the treatment of patients with bone metastases as they delay the
      onset and reduce the risk of skeletal-related events and also palliate or control
      bone pain in multiple cancer types, thus preserving quality of life. Zoledronic
      acid has proven efficacy and safety in patients with bone lesions from breast
      cancer, prostate cancer, lung cancer, and other solid tumors, as well as in
      patients with multiple myeloma. Current data suggest that early treatment with
      zoledronic acid (before the onset of bone pain) may provide additional clinical
      benefits and also positive effects on survival in subsets of patients who have
      elevated levels of N-telopeptide of type I collagen (NTX), a biochemical marker
      of bone resorption. Studies have shown that in patients with breast cancer,
      prostate cancer, lung cancer, or other solid tumors, normalization of elevated
      levels of NTX was observed in the majority of patients who received zoledronic
      acid. Furthermore, normalization of NTX values correlated with extended survival.

PMID- 18068487
TI  - Safety profile of intravenous bisphosphonates.
AB  - Because of their proven efficacy, intravenous bisphosphonates play an important
      role in reducing the risk of skeletal-related events including pathologic
      fractures, spinal cord compression, and palliative radiotherapy to bone in
      patients with malignant bone lesions. Overall, intravenous bisphosphonates have
      an acceptable safety profile and are commonly associated with transient and
      manageable flu-like symptoms after initial infusions. In addition,
      bisphosphonates have dose- and infusion rate-dependent effects on renal function
      that can be proactively managed in patients with reduced creatinine clearance
      rates by following recommended dosing guidelines. Recently, there have been
      reports of osteonecrosis of the jaw (ONJ) in patients with advanced cancer
      receiving complex chemotherapeutic treatment regimens and supportive care with
      bisphosphonates. ONJ prevention and management recommendations have been
      developed that may reduce the risk of ONJ and the impact of ONJ on quality of
      life. Moreover, bisphosphonate therapy has resulted in considerable clinical
      benefits in patients with malignant bone disease; therefore, the potential for
      adverse events such as ONJ must be placed into context with these meaningful
      benefits.

PMID- 18068488
TI  - Management of bisphosphonate treatment in clinical practice.
AB  - Bisphosphonates have become important tools for the treatment of bone lesions
      from various solid tumors or from multiple myeloma. Management of bone health in
      patients with malignant bone disease from breast cancer, prostate cancer, lung
      cancer, and multiple myeloma was discussed in clinical case workshops held during
      the ZENITH meeting (April 2007, Prague, Czech Republic). Physicians in attendance
      were generally in agreement that bisphosphonate therapy is recommended for
      treatment of bone metastases and that treatment should be sustained over the
      duration of disease progression. Consensus is still evolving regarding the
      optimal duration of therapy and the emerging role of bisphosphonates in the
      management of bone loss in the adjuvant setting. Bisphosphonates have proven
      efficacy in reducing and delaying skeletal-related events in patients with bone
      metastases, and play a key role in preserving patient functional independence and
      quality of life. Furthermore, bisphosphonate therapy is a cost-effective strategy
      in the care of patients with bone metastases compared with the cost of treatment
      for fractures and other skeletal complications. Finally, communication with
      patients is critical to increase awareness of the benefits of bisphosphonate
      therapy. Increased patient involvement with treatment decisions will likely
      encourage patient compliance and thereby maximize clinical benefit from
      bisphosphonate therapy.

PMID- 18068489
TI  - Reducing the risk of cancer treatment-associated bone loss in patients with
      breast cancer.
AB  - Women with breast cancer, especially those receiving aromatase inhibitors, are at
      higher risk for bone loss and fracture. Postmenopausal women may already have
      multiple risk factors for fracture, and breast cancer therapies compound these
      risks. Current guidelines for bone health management in women with breast cancer
      are based on bone mineral density (BMD) measurements; however, many risk factors
      for fracture are independent of bone mineral density. Thus, consideration of
      other risk factors for fracture, including cancer therapies, aromatase inhibitor
      therapy, and age, may be necessary to accurately identify patients at high risk
      for bone loss. Bisphosphonates, inhibitors of osteoclast-mediated osteolysis, may
      be efficacious for the prevention of aromatase inhibitor-associated bone loss.
      Several clinical trials evaluating zoledronic acid in this setting have produced
      favorable results. In the Austrian Breast and Colorectal Cancer Study Group
      (ABCSG)-12 trial, patients receiving anastrozole or tamoxifen plus goserelin
      experienced significant bone loss, and zoledronic acid treatment prevented bone
      loss in both groups. Results from the parallel studies Z-FAST, ZO-FAST, and E-ZO
      FAST indicate that upfront zoledronic acid treatment increases BMD in patients
      receiving letrozole. These preliminary results are encouraging and suggest that
      zoledronic acid is an effective preventative therapy for bone loss in breast
      cancer patients receiving aromatase inhibitors.

PMID- 18068490
TI  - Meeting Report: NIH Workshop on the Tuberculosis Immune Epitope Database.
AB  - The Immune Epitope Database (IEDB), an online resource available at
      http://immuneepitope.org/, contains data on T cell and B cells epitopes of
      multiple pathogens, including M. tuberculosis. A workshop held in June, 2007
      reviewed the existing database, discussed the utility of reference sets of
      epitopes, and identified knowledge gaps pertaining to epitopes and immune
      responses in tuberculosis.

PMID- 18068492
TI  - Grappling with traumatic brain injury.

PMID- 18068491
TI  - The aerosol rabbit model of TB latency, reactivation and immune reconstitution
      inflammatory syndrome.
AB  - The large reservoir of human latent tuberculosis (TB) contributes to the global
      success of the pathogen, Mycobacterium tuberculosis (Mtb). We sought to test
      whether aerosol infection of rabbits with Mtb H37Rv could model paucibacillary
      human latent TB. The lung burden of infection peaked at 5 weeks after aerosol
      infection followed by host containment of infection that was achieved in all
      rabbits. One-third of rabbits had at least one caseous granuloma with culturable
      bacilli at 36 weeks after infection suggesting persistent paucibacillary
      infection. Corticosteroid-induced immunosuppression initiated after disease
      containment resulted in reactivation of disease. Seventy-two percent of rabbits
      had culturable bacilli in the right upper lung lobe homogenates compared to none
      of the untreated controls. Discontinuation of dexamethasone led to predictable
      lymphoid recovery, with a proportion of rabbits developing multicentric large
      caseous granuloma. The development and severity of the immune reconstitution
      inflammatory syndrome (IRIS) was dependent on the antigen load at the time of
      immunosuppression and subsequent bacillary replication during corticosteroid
      induced immunosuppression. Clinically, many aspects were similar to IRIS in
      severely immunosuppressed HIV-infected patients who have functional restoration
      of T cells in response to effective (highly active) antiretroviral therapy. This
      corticosteroid model is the only animal model of the IRIS. Further study of the
      rabbit model of TB latency, reactivation and IRIS may be important in
      understanding the immunopathogenesis of these poorly modeled states as well as
      for improved diagnostics for specific stages of disease.

PMID- 18068493
TI  - The humanitarian response index.

PMID- 18068494
TI  - Remembering the neglected tropical diseases.

PMID- 18068495
TI  - CETP inhibition.

PMID- 18068496
TI  - Baclofen for alcoholism.

PMID- 18068497
TI  - A wake-up call for global access to salvage HIV drug regimens.

PMID- 18068498
TI  - Time for a global partnership on non-communicable diseases.

PMID- 18068499
TI  - Screening for diabetes and prediabetes.

PMID- 18068500
TI  - Polyclinics in London.

PMID- 18068501
TI  - Should the internet be used to promote healthy living?

PMID- 18068502
TI  - Sania Nishtar: preventing chronic diseases in Pakistan.

PMID- 18068503
TI  - Global interest in addressing non-communicable disease.

PMID- 18068504
TI  - Integrating a new public health order.

PMID- 18068505
TI  - Should we undertake an MRI breast screening trial?

PMID- 18068507
TI  - Should we undertake an MRI breast screening trial?

PMID- 18068508
TI  - Should we undertake an MRI breast screening trial?

PMID- 18068509
TI  - CAIRO and FOCUS.

PMID- 18068510
TI  - A pinch of salt for convulsive status epilepticus.

PMID- 18068512
TI  - Global guidelines for nutrition support.

PMID- 18068513
TI  - Nutritional iron deficiency in patients with chronic illnesses.

PMID- 18068514
TI  - Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on
      lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure
      in healthy individuals: two double-blind, randomised placebo-controlled phase I
      studies.
AB  - BACKGROUND: The inhibition of cholesteryl ester transfer protein (CETP) is
      considered a potential new mechanism for treatment of dyslipidaemia. Anacetrapib
      (MK-0859) is a CETP inhibitor currently under development. We aimed to assess
      anacetrapib's effects as monotherapy on low-density lipoprotein cholesterol (LDL
      C) and high-density lipoprotein cholesterol (HDL-C) and on 24-h ambulatory blood
      pressure. METHODS: We did two double-blind, randomised, placebo-controlled phase
      I studies. In the first study, 50 patients with dyslipidaemia (LDL-C 100-190
      mg/dL; 40 active, 10 placebo) aged 18-75 years received anacetrapib doses of 0,
      10, 40, 150, or 300 mg orally once a day with a meal for 28 days. Standard lipid
      and lipoprotein monitoring, safety monitoring, and anacetrapib concentrations for
      pharmacokinetics were done. In the second study, 22 healthy participants aged 45
      75 years received either 150 mg of anacetrapib once a day or matching placebo
      with a meal for 10 days in each crossover period, in a randomised sequence, with
      at least a 14-day washout between the treatment periods. Continuous 24-h
      ambulatory blood pressure monitoring was done on day -1 and day 10 of each
      treatment period in this study. The primary or secondary endpoints of safety and
      tolerability were assessed in both studies by monitoring clinical adverse
      experiences, physical examinations, vital signs, 12-lead electrocardiogram, and
      laboratory safety. Analysis was per protocol. These trials are registered with
      ClinicalTrials.gov, number NCT00565292 and NCT00565006. FINDINGS: In the
      dyslipidaemia study, one patient withdrew consent and one was excluded from the
      data analysis for HDL-C and LDL-C because complete pre-dose measurements were not
      available. Anacetrapib produced dose-dependent lipid-altering effects with peak
      lipid-altering effects of 129% (mean 51.1 [SD 3.8]-114.9 [7.9] mg/dL) increase in
      HDL-C and a 38% (138.2 [11.4]-77.6 [7.9] mg/dL) decrease in LDL-C in patients
      with dyslipidaemia. In the 24-h ambulatory blood pressure study in healthy
      individuals, least squares difference between anacetrapib and placebo groups on
      day 10 were 0.60 (90% CI -1.54 to 2.74; p=0.634) mm Hg for systolic blood
      pressure and 0.47 (90% CI -0.90 to 1.84; p=0.561) mm Hg for diastolic blood
      pressure. INTERPRETATION: Anacetrapib seems to exhibit HDL-C increases greater
      than those seen with other investigational drugs in this class and LDL-C lowering
      effects similar to statins. Despite greater lipid-altering effects relative to
      other members of this class, anacetrapib seems not to increase blood pressure,
      suggesting that potent CETP inhibition by itself might not lead to increased
      blood pressure.

PMID- 18068515
TI  - Effectiveness and safety of baclofen for maintenance of alcohol abstinence in
      alcohol-dependent patients with liver cirrhosis: randomised, double-blind
      controlled study.
AB  - BACKGROUND: Intervention to achieve alcohol abstinence represents the most
      effective treatment for alcohol-dependent patients with liver cirrhosis; however,
      anticraving drugs might worsen liver disease. We aimed to investigate the
      effectiveness and safety of baclofen in achieving and maintaining alcohol
      abstinence in patients with liver cirrhosis. METHODS: Between October, 2003, and
      November, 2006, 148 alcohol-dependent patients with liver cirrhosis were referred
      to the Institute of Internal Medicine, Rome, Italy. 84 were randomly allocated
      either oral baclofen or placebo for 12 weeks. Primary outcome was proportion of
      patients achieving and maintaining alcohol abstinence. Measures of this outcome
      were total alcohol abstinence and cumulative abstinence duration, which were
      assessed at outpatient visits. Relapse was defined as alcohol intake of more than
      four drinks per day or overall consumption of 14 or more drinks per week over a
      period of at least 4 weeks. Analysis was by intention to treat. This study is
      registered with ClinicalTrials.gov, number NCT00525252. FINDINGS: Of 42 patients
      allocated baclofen, 30 (71%) achieved and maintained abstinence compared with 12
      (29%) of 42 assigned placebo (odds ratio 6.3 [95% CI 2.4-16.1]; p=0.0001). The
      number of dropouts (termination of treatment) did not differ between the baclofen
      (6/42 [14%]) and placebo (13/42 [31%]) groups (p=0.12). Cumulative abstinence
      duration was about twofold higher in patients allocated baclofen than in those
      assigned placebo (mean 62.8 [SE 5.4] vs 30.8 [5.5] days; p=0.001). No hepatic
      side-effects were recorded. INTERPRETATION: Baclofen is effective at promoting
      alcohol abstinence in alcohol-dependent patients with liver cirrhosis. The drug
      is well tolerated and could have an important role in treatment of these
      individuals.

PMID- 18068516
TI  - Risk of extensive virological failure to the three original antiretroviral drug
      classes over long-term follow-up from the start of therapy in patients with HIV
      infection: an observational cohort study.
AB  - BACKGROUND: The long-term durability of viral-load suppression provided by the
      three original antiretroviral drugs is not well characterised. We estimated the
      proportion of patients who had extensive triple-class failure during long-term
      follow-up and examined characteristics associated with an increased rate of
      failure. METHODS: 7916 patients who started antiretroviral therapy with three or
      more drugs were followed up from the time that therapy started until the last
      viral-load measure. Extensive triple-class virological failure was defined by
      failure of three subclasses of nucleoside reverse transcriptase inhibitors, a non
      nucleoside reverse transcriptase inhibitor, and a ritonavir-boosted protease
      inhibitor. FINDINGS: 167 patients developed extensive triple-class failure during
      27 441 person-years of follow-up. The Kaplan-Meier estimate for the cumulative
      risk of extensive triple-class failure was 9.2% by 10 years (95% CI 5.0-13.4).
      There was evidence that this rate has decreased over time (adjusted hazard ratio
      0.86 [0.77-0.96] per year more recent; p=0.006). Of the 167 patients with
      extensive triple-class failure, 101 (60%) subsequently had at least one viral
      load less than 50 copies per mL. The risk of death by 5 years from the time of
      extensive triple-class failure was 10.6% (2.4-18.8, nine deaths). INTERPRETATION:
      We have shown that extensive virological failure of the three main classes of
      drugs occurs slowly in routine clinical practice. This finding has implications
      for the planning of treatment programmes in developing countries, where
      additional drugs outside these classes are unlikely to be available for some
      time.

PMID- 18068517
TI  - Health outcomes of bereavement.
AB  - In this Review, we look at the relation between bereavement and physical and
      mental health. Although grief is not a disease and most people adjust without
      professional psychological intervention, bereavement is associated with excess
      risk of mortality, particularly in the early weeks and months after loss. It is
      related to decrements in physical health, indicated by presence of symptoms and
      illnesses, and use of medical services. Furthermore, bereaved individuals report
      diverse psychological reactions. For a few people, mental disorders or
      complications in the grieving process ensue. We summarise research on risk
      factors that increase vulnerability of some bereaved individuals. Diverse factors
      (circumstances of death, intrapersonal and interpersonal variables, ways of
      coping) are likely to co-determine excesses in ill-health. We also assess the
      effectiveness of psychological intervention programmes. Intervention should be
      targeted at high-risk people and those with complicated grief or bereavement
      related depression and stress disorders.

PMID- 18068518
TI  - Thunderclap headache--and a tender neck.

PMID- 18068519
TI  - An aspirin a day for Alzheimer's disease?

PMID- 18068520
TI  - Active convulsive epilepsy in a rural district of Kenya: a study of prevalence
      and possible risk factors.
AB  - BACKGROUND: Few large-scale studies of epilepsy have been done in sub-Saharan
      Africa. We aimed to estimate the prevalence of, treatment gap in, and possible
      risk factors for active convulsive epilepsy in Kenyan people aged 6 years or
      older living in a rural area. METHODS: We undertook a three-phase screening
      survey of 151,408 individuals followed by a nested community case-control study.
      Treatment gap was defined as the proportion of cases of active convulsive
      epilepsy without detectable amounts of antiepileptic drugs in blood. FINDINGS:
      Overall prevalence of active convulsive epilepsy was 2.9 per 1000 (95% CI 2.6
      3.2); after adjustment for non-response and sensitivity, prevalence was 4.5 per
      1000 (4.1-4.9). Substantial heterogeneity was noted in prevalence, with evidence
      of clustering. Treatment gap was 70.3% (65.9-74.5), with weak evidence of a
      difference by sex and area. Adjusted odds of active convulsive epilepsy for all
      individuals were increased with a family history of non-febrile convulsions (odds
      ratio 3.3, 95% CI 2.4-4.7; p<0.0001), family history of febrile convulsions
      (14.6, 6.3-34.1; p<0.0001), history of both seizure types (7.3, 3.3-16.4;
      p<0.0001), and previous head injury (4.1, 2.1-8.1; p<0.0001). Findings of
      multivariable analyses in children showed that adverse perinatal events (5.7, 2.6
      12.7; p<0.0001) and the child's mother being a widow (5.1, 2.4-11.0; p<0.0001)
      raised the odds of active convulsive epilepsy. INTERPRETATION: Substantial
      heterogeneity exists in prevalence of active convulsive epilepsy in this rural
      area in Kenya. Assessment of prevalence, treatment use, and demographic variation
      in screening response helped to identify groups for targeted interventions.
      Adverse perinatal events, febrile illness, and head injury are potentially
      preventable associated factors for epilepsy in this region.

PMID- 18068521
TI  - Estimations of the prevalence of epilepsy in sub-Saharan Africa.

PMID- 18068522
TI  - Aspirin in Alzheimer's disease (AD2000): a randomised open-label trial.
AB  - BACKGROUND: Cardiovascular risk factors and a history of vascular disease can
      increase the risk of Alzheimer's disease (AD). AD is less common in aspirin users
      than non-users, and there are plausible biological mechanisms whereby aspirin
      might slow the progression of either vascular or Alzheimer-type pathology. We
      assessed the benefits of aspirin in patients with AD. METHODS: 310 community
      resident patients who had AD and who had no potential indication or definite
      contraindication for aspirin were randomly assigned to receive open-label aspirin
      (n=156; one 75-mg enteric-coated tablet per day, to continue indefinitely) or to
      avoid aspirin (n=154). Primary outcome measures were cognition (assessed with the
      mini-mental state examination [MMSE]) and functional ability (assessed with the
      Bristol activities of daily living scale [BADLS]). Secondary outcomes were time
      to formal domiciliary or institutional care, progress of disability, behavioural
      symptoms, caregiver wellbeing, and care time. Patients were assessed at 12-week
      intervals in the first year and once each year thereafter. Analysis of the
      primary outcome measures was by intention to treat. This study is registered as
      an International Standard Randomised Controlled Trial, number ISRCTN96337233.
      FINDINGS: Patients had a median age of 75 years; 156 patients had mild AD, 154
      had moderate AD, and 18 had concomitant vascular dementia. Over the 3 years after
      randomisation, in patients who took aspirin, mean MMSE score was 0.10 points
      higher (95% CI -0.37 to 0.57; p=0.7) and mean BADLS score was 0.62 points lower (
      1.37 to 0.13; p=0.11) than in patients assigned to aspirin avoidance. There were
      no obvious differences between the groups in any other outcome measurements. 13
      (8%) patients on aspirin and two (1%) patients in the control group had bleeds
      that led to admission to hospital (relative risk=4.4, 95% CI 1.5-12.8; p=0.007);
      three (2%) patients in the aspirin group had fatal cerebral bleeds.
      INTERPRETATION: Although aspirin is commonly used in dementia, in patients with
      typical AD 2 years of treatment with low-dose aspirin has no worthwhile benefit
      and increases the risk of serious bleeds.

PMID- 18068523
TI  - Erythrocyte and plasma fatty acid profiles in patients with epilepsy: does
      carbamazepine affect omega-3 fatty acid concentrations?
AB  - Fatty acids (FAs) determine membrane properties and may affect cardiac and
      neuronal function. In this study, FA profiles were determined in 56 patients with
      epilepsy who participated in a 12-week double-blind randomized trial of omega-3
      FA supplementation (1 g eicosapentaenoic acid and 0.7 g docosahexaenoic acid
      daily). At baseline, subjects on carbamazepine (CBZ) had lower docosahexaenoic
      acid levels, lower levels of long-chain omega-3 FAs, and a lower Omega-3 Index (a
      risk factor for coronary heart disease mortality), whereas those on oxcarbazepine
      had higher total polyunsaturated FAs and a higher Omega-3 Index. Following omega
      3 FA supplementation, the Omega-3 Index, eicosapentaenoic acid, and
      docosahexaenoic acid concentrations significantly increased. Patients on CBZ
      exhibited a less favorable FA profile, associated with a greater risk of coronary
      heart disease mortality. As arrhythmias are thought to be an important mechanism
      in coronary heart disease mortality and sudden unexplained death in epilepsy
      (SUDEP), the effect of CBZ effect in reducing omega-3 FAs might potentially
      explain some cases of SUDEP among patients prescribed CBZ.

PMID- 18068524
TI  - MTT2, a copper-inducible metallothionein gene from Tetrahymena thermophila.
AB  - Metallothioneins (MTs) are ubiquitous, cysteine-rich, metal-binding proteins
      whose transcriptional activation is induced by a variety of stimuli, in
      particular heavy metals such as cadmium, copper and zinc. Here we describe the
      sequence and organization of a novel copper-inducible metallothionein gene (MTT2)
      from Tetrahymena thermophila. Based on its deduced sequence, the gene encodes a
      protein 108 amino acids, containing 29 cysteine residues (30%) arranged in motifs
      characteristic of vertebrate and invertebrate MTs. We demonstrate that the 5'
      region of the MTT2 gene can act as an efficient promoter to drive the expression
      of heterologous genes in the Tetrahymena system. In the latter case, a gene for a
      candidate vaccine antigen against Ichthyophthirius multifiliis, a ubiquitous
      parasite of freshwater fish, was expressed at high levels in transformed T.
      thermophila cell lines. Moreover, the protein was properly folded and targeted to
      the plasma membrane in its correct three-dimensional conformation. This new
      copper-inducible MT promoter may be an attractive alternative to the cadmium
      inducible MTT1 promoter for driving ectopic gene expression in Tetrahymena and
      could have a great impact on biotechnological perspectives.

PMID- 18068525
TI  - FAS -1377 G/A polymorphism and the risk of lymph node metastasis in cervical
      cancer.
AB  - Single-nucleotide polymorphisms of the FAS -1377G/A, FAS -670A/G, and FASL 
      844T/C genes may alter transcriptional activity of these genes. Recent evidence
      suggests an association of these polymorphisms with an increased risk of cervical
      cancer, so we explored this relationship. Genotypes of 155 patients with cervical
      cancer and 160 healthy control subjects were determined using polymerase chain
      reaction-based restriction fragment length polymorphism (PCR-RFLP). Associations
      with cancer risk were estimated using two-sided logistic regression. We observed
      a significantly increased risk of lymph node metastasis associated with the FAS 
      1377 GA or AA polymorphism [odds ratio (OR) = 4.16, 95% confidence interval (CI)
      = 1.10 to 15.74; P = 0.036]. In addition, the FAS -670AG or GG genotype showed an
      increased incidence of node metastasis, but these findings were not statistically
      significant (OR = 3.67, 95% CI = 0.96-14.00, P = 0.059). There was no significant
      association between an increased risk of cervical cancer and polymorphisms of the
      death pathway genes FAS and FASL. None of the polymorphisms were associated with
      risk of advanced stage or histologic subtype of cervical cancer. In conclusion,
      FAS -1377 G-->A polymorphism may be associated with an increased risk of lymph
      node metastasis in Korean cervical cancer patients.

PMID- 18068526
TI  - Identification of polymorphisms in the XIAP gene and analysis of association with
      lung cancer risk in a Korean population.
AB  - The X-linked inhibitor of apoptosis protein (XIAP) is a potent mammalian IAP, and
      has been shown to play an important role in development and progression of
      cancer. Polymorphisms in the XIAP gene may influence XIAP production or activity,
      thereby modulating susceptibility to lung cancer. To test this hypothesis, we
      first screened for polymorphisms in the XIAP gene by direct sequencing of genomic
      DNA samples from 27 healthy Korean women and then performed a case-control study
      to evaluate the association between the polymorphisms and the risk of lung
      cancer. The XIAP genotypes were determined by polymerase chain reaction
      amplification and melting curve analysis in 582 lung cancer patients and in 582
      healthy control subjects who were frequency-matched for age and sex. We
      identified 12 single nucleotide polymorphisms (SNPs), one novel SNP [30051C>G
      (A321G) in exon 3] and the following 11 known SNPs: 192G>C (rs5956578), 262C>T
      (rs28382699), 318C>T (rs5958318), and 374C>T (rs12687176) in the putative
      promoter; 26615A>G (rs2355676) in intron 1; 41725A>G (rs5958338) in intron 5;
      42009A>C (Q423P, rs5956583) in exon 6; 48162T>C (rs17334739) and 48228C>T
      (rs28382739) in intron 6; and 48542A>G (rs28382740) and 49333G>T (rs28382742) in
      3'-UTR. Four of these 12 SNPs were selected for large-scale genotyping based on
      their frequencies and haplotype tagging status: 262C>T, 318C>T, 374C>T, and
      42009A>C. The four XIAP polymorphisms and their haplotypes exhibited no apparent
      relationship with the risk of lung cancer. In addition, we observed no evidence
      of effect modification by age, sex, smoking history, or tumor histology. These
      results suggest that XIAP polymorphisms do not significantly affect
      susceptibility to lung cancer in Koreans.

PMID- 18068527
TI  - TP53 codon 72 polymorphism in susceptibility, overall survival, and adjuvant
      therapy response of gliomas.
AB  - TP53 is a key tumor suppressor gene that encodes a transcriptional factor
      involved in several cellular mechanisms, including growth arrest, DNA repair, and
      induction of apoptosis. In addition to TP53 gene mutations, a common
      polymorphism, Arg72Pro, has been involved in the carcinogenesis process. The
      Pro72 variant has been associated with a slower induction of apoptosis and may
      influence the risk of cancer development. The role of Arg72Pro polymorphism in
      glioma susceptibility is poorly characterized. With the objective of analyzing
      the role of the TP53 Arg72Pro polymorphism in glioma risk, overall survival, and
      patient therapy response in a Portuguese population, we conducted a retrospective
      case-control study, including 171 patients with gliomas and 526 cancer-free
      individuals. The Arg72Pro genotype was assessed by the polymerase chain reaction
      restriction fragment length polymorphism technique. No statistically significant
      differences were observed in the genotypic and allelic frequencies between glioma
      and control groups, and no statistically significant differences were observed
      with stratification of gliomas into distinct histological subtypes: astrocytic (n
      = 115), glioblastoma (n = 75), and oligodendroglial (n = 54) tumors. No
      significant association was observed between TP53 Arg72Pro and patient overall
      survival, but Kaplan-Meier analysis of glioma patients harboring the Pro72 allele
      showed a significantly longer survival with adjuvant therapy. In this first
      assessment of the role of TP53 Arg72Pro polymorphism in a large series of
      Portuguese glioma tumors, no association was observed with glioma susceptibility
      or overall survival, except for patients submitted to adjuvant therapy.

PMID- 18068528
TI  - Random aneuploidy in chronic hepatitis C patients.
AB  - Hepatitis C virus (HCV) has been recently recognized as a potential cause of B
      cell lymphoma. Both chronic hepatitis B and C with or without cirrhosis represent
      major preneoplastic conditions, and the majority of hepatocellular carcinomas
      arise in these pathological settings. According to the aneuploidy-cancer theory,
      carcinogenesis is initiated by random aneuploidy, which is either induced by
      carcinogens or arises spontaneously. The aim of this study was to evaluate random
      aneuploidy rate in HCV patients during chronic infection and remission (past
      infection eradicated), compared with non-Hodgkin lymphoma (NHL) patients and
      healthy controls. To determine random aneuploidy, we applied the FISH technique
      with probes for chromosomes 9 and 18. Significantly higher random aneuploidy rate
      was found in the HCV-infected and lymphoma patients than in the control group;
      the past HCV group in remission had intermediate rates, between those of the
      control group and the chronically infected patients. Patients who have eradicated
      HCV infection may nonetheless carry higher risk for future malignancy and
      therefore need long-term follow-up.

PMID- 18068529
TI  - Determination of ancestral allele for possible human cancer-associated
      polymorphisms.
AB  - To determine ancestral allele in possible cancer-associated polymorphisms, DNA
      samples from 10 chimpanzees (Pan troglodytes) were sequenced for alleles
      corresponding to 17 polymorphisms: 8 short tandem repeats [IL1RN (alias IL-1RA)
      variable number tandem repeat (VNTR); TYMS (previously TS) VNTR; AR CAG repeat;
      dinucleotide repeats of UGT1A1, IGF1, IFNG (alias IFN-gamma), ESR1 (alias ER
      alpha), and EGFR] and 9 single nucleotide polymorphisms (MMP1-1607 1G/2G, MMP3
      1171 5A/6A, OGG1 Ser326Cys, ALDH2 Gly487Lys, TP53 Arg72Pro, ABCG2 Gln141Lys, MGMT
      Leu84Phe, SOD2 Ala-9Val, and MTHFR Ala222Val). No chimpanzee polymorphism
      corresponded to human IL1RN VNTR; the ancestral allele was a repeat lost in
      humans. Dinucleotide repeat polymorphisms of IGF1, IFNG, ESR1, and EGFR were
      shared by chimpanzees, but the length of repeats tended to be longer in humans
      than in chimpanzees. This tendency was particularly evident for IGF1. All of the
      SNPs tested are human-specific nucleotide changes. The ancestral allele 7A was
      shown to be lost in MMP3-1171 5A/6A. Thus, all of the possible cancer-associated
      polymorphisms tested have human-specific alleles, and the ancestral allele is
      lost in three polymorphisms (IL1RN VNTR, UGT1A1 CA repeat, and MMP3-1171 5A/6A),
      suggesting a possible involvement of human-specific alleles in cancer
      susceptibility.

PMID- 18068530
TI  - CREB3L4, INTS3, and SNAPAP are targets for the 1q21 amplicon frequently detected
      in hepatocellular carcinoma.
AB  - High-density single nucleotide polymorphism (SNP) array analysis revealed novel
      amplification at 1q21 in cell lines derived from hepatocellular carcinomas
      (HCCs). Fluorescence in situ hybridization and real-time quantitative polymerase
      chain reaction studies verified amplification at 1q21. An increase in copy number
      at the region was detected in 32 of the 36 primary HCC tumors (89%). To identify
      the targets for amplification, we examined 19 HCC cell lines for expression
      levels of all 26 genes located within the 700-kb amplified region. Five genes
      were overexpressed in cell lines with amplification at 1q21. Among these, CREB3L4
      (cAMP responsive element binding protein 3-like 4), INTS3 (integrator complex
      subunit 3), and SNAPAP (SNAP-associated protein) were significantly overexpressed
      in tumors from 18 HCC patients, compared with counterpart nontumorous tissues.
      The findings suggest that CREB3L4, INTS3, and SNAPAP are probable targets for the
      amplification mechanism and may therefore be involved, together or separately, in
      the development or progression of HCCs.

PMID- 18068531
TI  - Disruption of the ETV6 gene as a consequence of a rare translocation
      (12;12)(p13;q13) in treatment-induced acute myeloid leukemia after breast cancer.
AB  - We describe a case of treatment-induced acute myeloid leukemia M2 after breast
      cancer with a rare reciprocal t(12;12)(p13;q13) as a secondary cytogenetic
      abnormality in addition to the t(11;19)(q23;p13.1). Fluorescence in situ
      hybridization analysis revealed that both ETV6 genes (previously TEL) were
      located on the same der(12)t(12;12) as a result of t(12;12). Interestingly, the
      translocated ETV6 gene was disrupted, indicating the breakpoint on the large
      der(12)t(12;12) to be within the ETV6 gene and thus the possible formation of a
      new fusion gene. CHOP gene at 12q13, was found to be translocated intact to the
      other homologue chromosome 12, indicating that the breakpoint on the small
      der(12) is proximal to CHOP. To the best of our knowledge, our patient represents
      the first report of the rare t(12;12)(p13;q13) described in treatment-induced
      leukemia and the possible formation of a new fusion gene.

PMID- 18068532
TI  - NUP98-NSD1 fusion by insertion in acute myeloblastic leukemia.
AB  - A case of NUP98-NSD1 gene fusion resulting from the insertion of a subtelomeric
      part of chromosome 11p15.4 within the subtelomeric part of 5q35 was detected in a
      child with acute myeloblastic leukemia. This new case illustrates the importance
      of using fluorescence in situ hybridization followed by reverse transcriptase
      polymerase chain reaction techniques to detect abnormalities involving
      subtelomeric chromosomal regions.

PMID- 18068533
TI  - Methylation of PTCH1, the Patched-1 gene, in a panel of primary medulloblastomas.
AB  - The Sonic hedgehog (Shh) pathway is aberrantly activated in a subset of the most
      common malignant pediatric brain tumor, medulloblastoma (MB). Shh pathway
      activity is measured by expression of the target genes in the GLI family, MYCN
      and PTCH1, a tumor suppressor and negative regulator of the pathway. Promoter
      methylation of tumor suppressors is implicated in tumor formation by gene
      silencing. In this study, we examined whether the proximal promoter of the PTCH1
      gene (variant exon 1B) is methylated in some cases of MB. The cases in which we
      anticipated the highest likelihood of methylation were chosen based on gene
      expression of indicators of Shh pathway activity. Of 21 primary MBs, four
      exhibited robust mRNA expression of GLI1 and MYCN as well as low or absent PTCH1
      expression, suggesting Shh pathway activity in the absence of PTCH1. The
      methylation profile of these cases was determined by the bisulfite sequencing
      method and compared to the profiles of five unaffected pediatric cerebellum
      controls. Contrary to our hypothesis, there was no evidence of methylation in the
      PTCH1-1B promoter in the MB cases examined, nor was there methylation in the
      control cerebellum samples. Future directions include examination of distal
      regions of the PTCHlb promoter as well as alternative exon variants, most notably
      the CpG island containing PTCH1-1C promoter.

PMID- 18068534
TI  - Polycythemia vera transforming to acute myeloid leukemia and complex
      abnormalities including 9p homogeneously staining region with amplification of
      MLLT3, JMJD2C, JAK2, and SMARCA2.
AB  - Polycythemia vera (PV) is a clonal stem cell disorder characterized by an
      excessive erythrocyte production. At diagnosis, a normal karyotype is found in <
      or =80% of cases, but an abnormal karyotype frequently develops with evolution.
      Trisomy 9 and gains on 9p are some of the most frequent cytogenetic
      abnormalities, together with trisomy 8 and del(20q) in both PV and idiopathic
      myelofibrosis. We report the case of a 54-year-old man whose disease was
      classified as an acute myeloid transformation of PV. Cytogenetic and multicolor
      fluorescence in situ hybridization (FISH) analysis detected several chromosomal
      abnormalities that included an amplification of 9p. Complementary FISH analysis
      established amplification of the 9p22 approximately p24.3 region including
      several known genes: MLLT3 (alias AF9), JMJD2C (alias GASC1), JAK2, and SMARCA2
      (alias BRM). JAK2(V617F) mutation status was quantitatively assessed by allele
      specific quantitative polymerase chain reaction. Although crossing points
      analysis showed JAK2(V617F) mutated alleles at 52%, it is still impossible to
      describe conclusively the mutational status of the amplified JAK2 gene within the
      sole homogeneously staining region, because total genomic DNA was extracted for
      the analysis and not only DNA from cells with the homogeneously staining region.
      Gains on 9p being among the most common anomalies in PV, amplification of a gene
      or genes on this region may play a crucial role in the pathogenesis or evolution
      of PV.

PMID- 18068535
TI  - Characterization of complex chromosome aberrations in a recurrent meningioma
      combining standard cytogenetic and array comparative genomic hybridization
      techniques.
AB  - Meningiomas were among the first solid tumors recognized as having cytogenetic
      alterations. The most consistent changes reported in grade I meningiomas were
      monosomy 22 or partial 22q deletion. The vast majority of meningiomas are
      histologically benign, but the prognosis is determined by risk of recurrence
      after surgical treatment. Despite important advances in the identification of
      prognostic factors in the past decade, the exact nature of tumor recurrence
      remains largely unknown. In the present study, a recurrent transitional
      meningioma deriving from the anterior portion of the falx cerebri was
      characterized by combining conventional cytogenetics and array comparative
      genomic hybridization (CGH). Cytogenetic analysis at diagnosis revealed the
      following complex numerical and structural aberrations:
      42,XY,der(1)t(1;?)(p12;?),-6,der(12;15)(q10;q10),-18, -22. Additional clonal
      evolutions were further identified with disease relapse. Array CGH corroborated
      the cytogenetic findings. The presence of a complex cytogenetic profile and
      progression-associated chromosomal abnormalities in a benign meningioma suggests
      the existence of underlying molecular events.

PMID- 18068536
TI  - Amplification of BCR-ABL and t(3;21) in a patient with blast crisis of chronic
      myelogenous leukemia.
AB  - The Philadelphia (Ph) chromosome, or t(9;22), is the hallmark of chronic
      myelogenous leukemia (CML). It results in juxtaposition of the 5' part of the BCR
      gene on chromosome 22 to the 3' part of the ABL1 gene (previously ABL) on
      chromosome 9. CML is clinically characterized by three distinct phases: chronic,
      accelerated, and blast phase. Blast crisis is characterized by the rapid
      expansion of a population of differentiation arrested blast cells (myeloid or
      lymphoid cells population), with secondary chromosomal abnormalities present. We
      report a case of myeloid blast crisis of CML resistant to imatinib mesylate and
      chemotherapy. By use of cytogenetic, fluorescence in situ hybridization, and
      comparative genomic hybridization methods, we identified a cluster of BCR-ABL
      amplification on inverted duplication of the Ph chromosome with t(3;21)(q26;q22)
      and increased genomic levels of the RUNX1 gene (previously AML1). The
      t(3;21)(q26;q22) is a recurrent chromosomal abnormality in some cases of CML
      blast phase and in treatment-related myelodysplastic syndrome and acute myeloid
      leukemia. Amplification or copy number increase of RUNX1 has been reported in
      childhood acute lymphoblastic leukemia. Our study indicated that the progenitor
      of CML was BCR-ABL dependent through the amplification of Ph chromosome as a
      mechanism of resistance to imatinib therapy. The coexistence of BCR-ABL and
      t(3;21)(q26;q22) with RUNX1 rearrangement might play a pivotal role in the CML
      blast transformation.

PMID- 18068537
TI  - A rare tumor and an ethical dilemma in a family with a germline TP53 mutation.
AB  - We describe a family with a history of cancer suggestive of the Li-Fraumeni
      syndrome (LFS). A 27-year-old woman suffered at 17 years of age from phyllodes
      breast tumor and was shown to carry a germline mutation in the TP53 gene. Two
      years after testing, she became pregnant and was offered prenatal diagnosis by
      her gynecologist. The patient expressed her commitment to deliver the baby
      regardless of its mutation status, but with a strong interest in having the child
      tested soon after the birth. When she was informed that testing of children is
      usually postponed until after they reach 18 years of age, she consulted several
      geneticists, who repeatedly discouraged her from the intent to test the newborn.
      In the end, the patient decided for prenatal genetic testing only to learn the
      mutation status of the child. This scenario being unacceptable, she was offered
      early postnatal testing of the child, and this analysis showed that the newborn
      boy carried the mutation. Based on this finding, the family was enrolled into a
      preventive screening program for childhood cancer. The case illustrates ethical
      problems associated with early predisposition testing in LFS, and the lack of
      consensus on this issue in the literature.

PMID- 18068538
TI  - Fusion of the COL1A1 and USP6 genes in a benign bone tumor.
AB  - Aneurysmal bone cyst (ABC) is a benign intraskeletal cyst that often expands
      rapidly and shows a strong tendency to recur. Rearrangement of chromosome band
      17p13 is a characteristic genetic feature of ABC, with t(16;17)(q22;p13) the most
      frequent chromosomal aberration. This translocation generates a CDH11-USP6 fusion
      gene in which the strong promoter of osteoblast cadherin 11 gene at 16q22 is
      fused to the entire ubiquitin-specific protease 6 coding sequence at 17p13. As a
      result, USP6 (alias Tre2) is transcriptionally upregulated. Fusion genes of
      several variant translocations have been reported in ABC, including a case with
      t(17;17) and COL1A1-USP6 fusion. In each translocation, the entire USP6 coding
      sequence is fused downstream to the promoter region of the partner gene. Here we
      report a second case of a bone tumor carrying a t(17;17) resulting in a COL1A1
      USP6 chimeric gene. As in the previous case, exon 1 of COL1A1 was fused to exon 2
      of USP6 in the chimeric transcript. A translation process of the hybrid
      transcript using the starting ATG codon of the COL1A1 gene results in a
      truncated, 38 amino acid residues variant of the COL1A1 peptide. Although a
      pathogenic effect of the small COL1A1 peptide cannot be ruled out, overexpression
      of USP6 through fusion with the COL1A1 promoter is a more reasonable hypothesis.

PMID- 18068539
TI  - Mutations of GATA1, FLT3, MLL-partial tandem duplication, NRAS, and RUNX1 genes
      are not found in a 7-year-old Down syndrome patient with acute myeloid leukemia
      (FAB-M2) having a good prognosis.
AB  - The prognosis of leukemia developed in Down syndrome (DS) patients has improved
      markedly. Most DS leukemia occurs before 3 years of age and is classified as
      acute megakaryocytic leukemia (AMKL). Mutations in the GATA1 gene have been found
      in almost all DS patients with AMKL. In contrast, it has been shown that
      occurrence of DS acute myeloid leukemia (DS-AML) after 3 years of age may
      indicate a higher risk for a poor prognosis, but its frequency is very low. Age
      is one of the significant prognostic indicators in DS-AML. The prognostic factor
      of gene alterations has not been reported in older DS-AML patients. We here
      describe the case of a 7-year-old DS boy with AML-M2, who had no history of
      transient abnormal myelopoiesis or any clinical poor prognostic factors, such as
      high white blood cell counts or extramedullary infiltration. We molecularly
      analyzed the GATA1, FLT3, MLL-partial tandem duplication, NRAS, and RUNX1
      (previously AML1) genes and did not detect any alterations. The patient has lived
      for more than 5 years after treatment on the AML99-Down protocol in Japan. This
      suggests that a patient lacking these genes alterations might belong to a
      subgroup of older DS-AML patients with good prognosis. Accumulation of more data
      on older pediatric DS-AML patients is needed.

PMID- 18068540
TI  - Loss of the extra chromosome 21 in a patient with Down syndrome and
      myelodysplasia.
AB  - Monosomy 21 is a rare acquired karyotypic abnormality associated with myeloid
      disorders. Occurrence of loss of one chromosome 21 in the background of trisomy
      21 in Down syndrome, resulting in the pseudo-normalization of trisomy 21, is a
      novel finding. The case is described of a patient with Down syndrome who acquired
      such a genetic abnormality as a result of myelodysplastic syndrome.

PMID- 18068541
TI  - Concomitant chronic myeloid leukemia and chronic lymphocytic leukemia: a
      different clonal origin shown by molecular cytogenetics.

PMID- 18068542
TI  - Translocation (8;21)(q22;q22) without rearrangement of RUNX1 and RUNX1T1 genes in
      a patient with refractory anemia with excess of blasts.

PMID- 18068543
TI  - How early to test for a cancer-causing germline mutation.

PMID- 18068544
TI  - Involvement of accumulated NOS inhibitors and endothelin-1, enhanced arginase,
      and impaired DDAH activities in pulmonary dysfunction following subarachnoid
      hemorrhage in the rabbit.
AB  - We designed the present experiments to investigate the involvement of endogenous
      nitric oxide synthase (NOS) inhibitors, dimethylarginine dimethylaminohydrolase
      (DDAH) as a hydrolyzing enzyme of the NOS inhibitors, NOS, arginase which shares
      l-arginine as a common substrate with NOS, and endothelin-1 (ET-1) in the
      pulmonary dysfunction after induction of experimental subarachnoid hemorrhage
      (SAH) in the rabbit. SAH was induced by injecting autologous blood into the
      cisterna magna, and controls were injected with saline. On day 2, pulmonary
      arteries were isolated for determinations. A significant impairment of the
      endothelium-dependent relaxation (EDR) caused by acetylcholine was found in 20
      cases (43.5%) out of 46 SAH animals, and the same animals exhibited accompanying
      the significantly impaired cyclic GMP production, accumulated endogenous NOS
      inhibitors, attenuated DDAH activity, enhanced arginase activity and accumulated
      ET-1 within the vessel wall. Meanwhile, there were no differences in endothelial
      NOS activity per se and sodium nitroprusside-induced relaxation between the
      animals with an impaired EDR and those without such a change. ET-1 content within
      aortic wall was increased with concomitant decrease in cyclic GMP production
      after the intraperitoneal application of authentic monomethylarginine as a NOS
      inhibitor in the rat. The current results suggest that accumulated endogenous NOS
      inhibitors and enhanced arginase activity possibly bring about the impaired NO
      production, thereby attenuating the EDR and contributing to the accumulation of
      ET-1 within the vessel wall. The accumulated endogenous NOS inhibitors at least
      partly result from the decreased DDAH activity. These alterations may be relevant
      to the pulmonary dysfunction after induction of SAH.

PMID- 18068545
TI  - Investigation of specificity of auricular acupuncture points in regulation of
      autonomic function in anesthetized rats.
AB  - Auricular acupuncture has been used for various autonomic disorders in clinical
      practice. It has been theorized that different auricular areas have distinct
      influence on autonomic functions. The present study aims to examine the effects
      of acupuncture stimulation at different auricular areas on cardiovascular and
      gastric responses. In male Sprague-Dawley rats anesthetized with pentobarbital
      sodium, five auricular areas, which were located at the apex of the helix (A(1)),
      the middle of the helix (A(2)), the tail of the helix (A(3)), the inferior concha
      (A(4)) and the middle of the antihelix (A(5)), had been selected for stimulation
      with manual acupuncture (MA) and different parameters of electroacupuncture (EA).
      A mild depressor response (6%-12% decrease from baseline) was evoked from A(1),
      A(3) and A(4) by MA and from all five areas by EA (100 Hz-1 mA). The biggest
      depressor response (-18.4+/-3.1 mmHg, p<0.001) was evoked from A(4). A small
      bradycardia was evoked by MA from A(4) and by EA at A(3), A(4) and A(5.) Increase
      in intragastric pressure (8-14 mmH(2)O) was evoked by MA from A(1), A(3) and A(4)
      and by EA at A(2.) These results show that similar patterns of cardiovascular and
      gastric responses could be evoked by stimulation of different areas of the
      auricle. The present results do not support the theory of a highly specific
      functional map in the ear. Rather, there is a similar pattern of autonomic
      changes in response to auricular acupuncture, with variable intensity depending
      on the area of stimulation.

PMID- 18068546
TI  - A web based resource characterizing the zebrafish developmental profile of over
      16,000 transcripts.
AB  - Using a spotted 65-mer oligonucleotide microarray, we have characterized the
      developmental expression profile from mid-gastrulation (75% epiboly) to 5 days
      post-fertilization (dpf) for >16,000 unique transcripts in the zebrafish genome.
      Microarray profiling data sets are often immense, and one challenge is validating
      the results and prioritizing genes for further study. The purpose of the current
      study was to address such issues, as well as to generate a publicly available
      resource for investigators to examine the developmental expression profile of any
      of the over 16,000 zebrafish genes on the array. On the chips, there are 16,459
      printed spots corresponding to 16,288 unique transcripts and 172 beta-actin
      (AF025305) spots spatially distributed throughout the chip as a positive control.
      We have collected 55 microarray gene expression profiling results from various
      zebrafish laboratories and created a Perl/CGI-based software tool
      (http://serine.umdnj.edu/approximately ouyangmi/cgi-bin/zebrafish/profile.htm)
      for researchers to look for the expression patterns of their gene of interest.
      Users can search for their genes of interest by entering the accession numbers or
      the nucleotide sequences and the expression profiling will be reported in the
      form of expression intensities versus time-course graphical displays. In order to
      validate this web tool, we compared 74 genes' expression results between our web
      tool and the in situ hybridization results from Thisse et al. [Thisse, B., Heyer,
      V., Lux, A., Alunni, A., Degrave, A., Seiliez, I., Kirchner, J., Parkhill, J.-P.,
      Thisse, C., 2004. Spatial and temporal expression of the zebrafish genome by
      large-scale in situ hybridization screening. Meth. Cell. Biol. 77, 505-519] as
      well as those reported by Mathavan et al. [Mathavan, S., Lee, S.G., mark, A.,
      Miller, L.D., Murthy, K.R., Tong, Y., Wu, Y.L., Lam, S.H., Yang, H., Ruan, Y.,
      Korzh, V., Gong, Z., Liu, E.T., Lufkin, T., 2005. Transcriptome analysis of
      zebrafish embryogenesis using microarrays. PLoS Genet. 1, 260-276]. The
      comparison indicates that our microarray-derived expression patterns are 80% and
      75% in agreement with the in situ database (Thisse et al., 2004) and previously
      published microarray data (Mathavan et al., 2005), respectively. Those genes that
      conflict between our web tool and the in situ database either have high sequence
      similarity with other genes or the in situ probes are not reliable. Among those
      genes that disagree between our web tool and those reported by Mathavan et al.
      (2005), 93% of the genes are in agreement between our web tool and the in situ
      database, indicating our web tool results are quite reliable. Thus, this resource
      provides a user-friendly web based platform for researchers to determine the
      developmental profile of their gene of interest and to prioritize genes
      identified in microarray analyses by their developmental expression profile.

PMID- 18068547
TI  - Spectroelectrochemistry of the redox activation of anti-cancer drug mitoxantrone.
AB  - The redox behaviour of the anti-cancer drug mitoxantrone was investigated in
      aprotic media (dimethylsulfoxide-DMSO) by coupled electrochemical and spectral
      EPR and UV/VIS absorption techniques. The cyclic voltammetry study with
      stationary and rotating disc electrode (RDE) of the reductive pathway of
      mitoxantrone points to two-electron transfers and evidences as intermediate
      species the anion radical, the dianion and the corresponding protonated species.
      EPR and optical spectra registered during the electrochemical reduction allow the
      identification of these species and suggest the possibility of back oxidation of
      the drug by electron transfer to molecular oxygen. The possibility of reductive
      activation of molecular oxygen by the intermediate species in the redox processes
      of mitoxantrone is discussed in connection with the cardiotoxicity of the drug.
      Gas phase and solvent-dependent AM1 and PM3 semiempirical MO calculations allow a
      rationalization of the experimental results regarding the reactivity in redox
      processes.

PMID- 18068553
TI  - Adiponectin and body composition in cystic fibrosis.
AB  - The aim of the study was to evaluate adiponectin (AD) serum concentrations in 43
      stable CF patients and 27 healthy subjects and to correlate them with their
      nutritional status. Body Composition (Bioelectrical Impedance),
      visceral/subcutaneous adipose tissue (VAT-SAT) in CF patients (CT-scan at L4),
      insulin resistance (HOMA-IR) and AD serum concentrations (ELISA) were studied. CF
      patients and controls had comparable weight, height, %BF, %FFM, fasting glucose,
      insulin and insulin resistance. CF patients had significantly lower BMI-SDS. CF
      males had higher %FFM and total FFM and lower %BF and total BF than females
      (p<0.001). Serum AD was higher in CF patients than controls (11.53+/-5.37 vs.
      9.07+/-4.41 microg/ml) and comparable between females and males. AD was lowest
      among young malnourished patients (8.06+/-1.85 microg/ml) and highest among young
      patients with normal nutrition (14.56+/-7.69 microg/ml). Patients with biliary
      cirrhosis had higher levels than patients with normal liver (10.52+/-5.49 vs.
      14.04+/-4.52 mug/ml, p<0.05). AD correlated with %BF, %FFM, FFM (kg) (p<0.05).VAT
      was significantly increased in malnourished patients. AD was not affected by VAT.
      CONCLUSIONS: Adiponectin is higher in CF patients than healthy individuals. It is
      decreased in malnourished young patients and increased in patients with normal
      nutrition and in patients with liver disease. This may be attributed to the
      reduced BF and to the energy deficit inherent to the disease.

PMID- 18068554
TI  - Respiratory system inertance corresponds to extravascular lung water in
      surfactant-deficient piglets.
AB  - In various cardio-pulmonary diseases lung mass is considerably increased due to
      intrapulmonary fluid accumulation, i.e. extravascular lung water (EVLW).
      Generally, inertance is a physical system parameter that is mass-dependent. We
      hypothesized that changes in lung mass influence the inertive behavior of the
      respiratory system. EVLW and intrathoracic blood volume (ITBV) were compared with
      respiratory system inertance (I(rs)) in four piglets before and after broncho
      alveolar lavage (BAL) that induced surfactant deficiency with interstitial edema.
      EVLW and ITBV were determined using the double-indicator dilution technique,
      I(rs) by multiple linear regression analysis. Measurements were taken before, and
      1 and 2 h after BAL. EVLW increased threefold (from 6.2+/-0.8 mL/kg at baseline
      to 17.7+/-0.9 mL/kg (p < 0.001) after BAL). I(rs) increased by 35% (from 0.17+/
      0.02 to 0.23+/-0.04 cmH(2)O s(2)/L (p = 0.036) after BAL) and was tightly
      correlated to EVLW (r(2) = 0.95, p < 0.023). ITBV did not change significantly
      after BAL. We conclude that I(rs) reflects actual changes in lung mass and thus
      hints at fluid accumulation within the lung.

PMID- 18068555
TI  - Shuttle walking versus maximal cycle testing: clinical correlates in patients
      with kyphoscoliosis.
AB  - A cross-sectional prospective design was used to compare the effectiveness of the
      shuttle walking test (SWT) and the maximal cycle ergometry test (CET) to assess
      the functional capacity of patients with chronic hypercapnic respiratory failure
      due to severe kyphoscoliosis. Twenty-four patients completed both the SWT and
      CET. Heart rate, blood pressure, leg fatigue, chest pain and dyspnea (Borg's
      scale) were measured immediately after each test. Correlation coefficients and
      Bland-Altman analysis were used to compare the two methods. Borg's dyspnea, leg
      and chest pain after exercise were not significantly different between tests.
      Only heart rate (SWT 130[20.7] versus CET 116[28.75]; p = 0.048) and diastolic
      blood pressure (SWT: 85.5[13.75] versus CET 95[17.5]; p = 0.021) were slightly
      but significantly different between the two protocols. There was a good positive
      correlation between the distance walked in SWT and maximal oxygen consumption (r
      = 0.675; p < 0.001). SWT and CET testing elicited similar clinical and
      hemodynamic responses. SWT is a feasible measure of functional capacity in this
      patient group.

PMID- 18068556
TI  - Chronic hypoxic hypercapnia modifies in vivo and in vitro ventilatory
      chemoreflexes in the cane toad.
AB  - Previous studies have shown that exposure to chronic hypoxia (CH) and chronic
      hypercapnia (CHC) alone have opposite effects on central respiratory-related
      pH/CO(2) chemosensitivity in the cane toad (Bufo marinus). This study examined
      the effects of chronic hypoxic hypercapnia (CHH) on central pH/CO(2)
      chemosensitivity. Cane toads were maintained at 10% O(2) and 3.5% CO(2) for 10
      days. Changes in central pH/CO(2)-sensitive fictive breathing were measured using
      in vitro brainstem-spinal cord preparations. Whole animal experiments examined
      the effects of CHH on in vivo ventilatory responses. In vitro, CHH augmented
      fictive breathing frequency but attenuated the integrated fictive breath area
      such that total fictive breathing was not altered. The effects on frequency were
      mediated by changes in the number of episodes/min rather than breaths/episode. In
      vivo, CHH blunted the ventilatory response to severe hypoxia and moderate
      hypercapnia. The results indicate that CHH alters breathing pattern in response
      to central chemoreceptor stimulation in vitro and modifies in vivo ventilatory
      chemoreflexes.

PMID- 18068557
TI  - Effect of IDA and TREN chelating agents and buffer systems on the purification of
      human IgG with immobilized nickel affinity membranes.
AB  - The purification of IgG from human plasma was studied by comparing two affinity
      membranes complexed with Ni(II), prepared by coupling iminodiacetic acid (IDA)
      and Tris(2-aminoethyl)amine (TREN) to poly(ethylenevinyl alcohol), PEVA, hollow
      fiber membranes. The Ni(II)-TREN-PEVA hollow fiber membrane had lower capacity
      for human IgG than the complex Ni(II)-IDA-PEVA, but with similar selectivity. The
      IgG in peak fractions eluted from the Ni(II)-IDA-PEVA with a stepwise
      concentration gradient of Tris-HCl pH 7.0 (100-700 mM) reached a purity of 98%
      (based on IgG, IgM, IgA, albumin, and transferrin nephelometric analysis).
      Adsorption IgG data at different temperatures (4-37 degrees C) were analyzed
      using Langmuir model resulting in a calculated maximum capacity at 25 degrees C
      of 204.6 mg of IgG/g of dry membrane. Decrease in Kd with increasing temperature
      (1.7x10(-5) to 5.3x10(-6) M) indicated an increase in affinity with increased
      temperature. The positive value of enthalpy change (26.2 kJ/mol) indicated that
      the adsorption of IgG in affinity membrane is endothermic. Therefore, lower
      temperature induces adsorption as verified experimentally.

PMID- 18068558
TI  - Determination of urinary phytoestrogens by HPLC-MS/MS: a comparison of
      atmospheric pressure chemical ionization (APCI) and electrospray ionization
      (ESI).
AB  - A comparison of the analytical performance of atmospheric pressure chemical
      ionization (APCI) and electrospray ionization (ESI) for the quantitative
      determination of six urinary phytoestrogens (daidzein, O-desmethylangolensin,
      equol, enterodiol, enterolactone and genistein) by high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) is presented here. Both APCI
      and ESI were suitable for the analysis of these compounds; however, ESI did
      improve measurement imprecision and sensitivity in certain cases. Method
      imprecision (between-run coefficients of variation [CVs] from duplicate analysis
      of three quality control [QC] urine pools across 20 runs) was 5.6-12% for ESI, as
      opposed to 5.3-30% for APCI. At low concentrations (3-60 ng/mL, analyte
      dependent) imprecision was lower with ESI, whereas both techniques were generally
      commensurate at high concentrations (200-1000 ng/mL, analyte dependent). Method
      accuracy (spiked analyte recovery from the QC pools) was comparable between
      techniques: 86-114% for ESI; 95-105% for APCI. Limits of detection (LODs) were
      equivalent or better with ESI compared to APCI, with the most significant LOD
      improvement observed for equol (ESI: 0.3 ng/mL; APCI: 2.7 ng/mL). This translated
      into a substantial increase in equol detection frequency (% of sample results
      above LOD) within a random patient sample subset (98% for ESI, compared to 81%
      for APCI, n=378). Correlation (Pearson) and agreement (Deming regression, Bland
      Altman bias) between ESI and APCI results in the patient subset was better in
      cases where imprecision and sensitivity was similar for both techniques
      (daidzein, enterolactone, genistein: r=0.993-0.998; slope=0.98-1.03; bias=-4.2 to
      -0.8%); correlation and/or agreement was poorer for analytes, where APCI
      imprecision and sensitivity were inferior (equol, O-desmethylangolensin,
      enterodiol). Baring significant factors arising from differences in ionization
      source design, these observations suggest that ESI is more appropriate for
      urinary biomonitoring of these compounds by LC-MS/MS.

PMID- 18068559
TI  - Preface: acute and chronic venous disease. Current status and future directions.

PMID- 18068560
TI  - Acute venous disease: venous thrombosis and venous trauma.
AB  - Acute venous disorders include deep venous thrombosis, superficial venous
      thrombophlebitis, and venous trauma. Deep venous thrombosis (DVT) most often
      arises from the convergence of multiple genetic and acquired risk factors, with a
      variable estimated incidence of 56 to 160 cases per 100,000 population per year.
      Acute thrombosis is followed by an inflammatory response in the thrombus and vein
      wall leading to thrombus amplification, organization, and recanalization.
      Clinically, there is an exponential decrease in thrombus load over the first 6
      months, with most recanalization occurring over the first 6 weeks after
      thrombosis. Pulmonary embolism (PE) and the post-thrombotic syndrome (PTS) are
      the most important acute and chronic complications of DVT. Despite the
      effectiveness of thromboembolism prophylaxis, appropriate measures are utilized
      in as few as one-third of at-risk patients. Once established, the treatment of
      venous thromboembolism (VTE) has been defined by randomized clinical trials, with
      appropriate anticoagulation constituting the mainstay of management. Despite its
      effectiveness in preventing recurrent VTE, anticoagulation alone imperfectly
      protects against PTS. Although randomized trials are currently lacking, at least
      some data suggests that catheter-directed thrombolysis or combined pharmaco
      mechanical thrombectomy can reduce post-thrombotic symptoms and improve quality
      of life after acute ileofemoral DVT. Inferior vena caval filters continue to have
      a role among patients with contra-indications to, complications of, or failure of
      anticoagulation. However, an expanded role for retrievable filters for relative
      indications has yet to be clearly established. The incidence of superficial
      venous thrombophlebitis is likely under-reported, but it occurs in approximately
      125,000 patients per year in the United States. Although the appropriate
      treatment remains controversial, recent investigations suggest that
      anticoagulation may be more effective than ligation in preventing DVT and PE.
      Venous injuries are similarly under-reported and the true incidence is unknown.
      Current recommendations include repair of injuries to the major proximal veins.
      If repair not safe or possible, ligation should be performed.

PMID- 18068561
TI  - The hemodynamics and diagnosis of venous disease.
AB  - The venous system is, in many respects, more complex than the arterial system and
      a thorough understanding of venous anatomy, pathophysiology, and available
      diagnostic tests is required in the management of acute and chronic venous
      disorders. The venous system develops through several stages, which may be
      associated with a number of development anomalies. A thorough knowledge of lower
      extremity venous anatomy, anatomic variants, and the recently updated
      nomenclature is required of all venous practitioners. Effective venous return
      from the lower extremities requires the interaction of the heart, a pressure
      gradient, the peripheral muscle pumps of the leg, and competent venous valves. In
      the absence of pathology, this system functions to reduce venous pressure from
      approximately 100 mm Hg to a mean of 22 mm Hg within a few steps. The severe
      manifestations of chronic venous insufficiency result from ambulatory venous
      hypertension, or a failure to reduce venous pressure with exercise. Although the
      precise mechanism remains unclear, venous hypertension is thought to induce the
      associated skin changes through a number of inflammatory mechanisms. Several
      diagnostic tests are available for the evaluation of acute and chronic venous
      disease. Although venous duplex ultrasonography has become the standard for
      detection of acute deep venous thrombosis, adjuvant modalities such as contrast,
      computed tomographic, and magnetic resonance venography have an increasing role.
      Duplex ultrasonography is also the most useful test for detecting and localizing
      chronic venous obstruction and valvular incompetence. However, it provides
      relatively little quantitative hemodynamic information and is often combined with
      measurements of hemodynamic severity determined by a number of plethysmographic
      methods. Finally, critical assessment of venous treatment modalities requires an
      understanding of the objective clinical outcome and quality of life instruments
      available.

PMID- 18068562
TI  - Primary chronic venous disorders.
AB  - Primary chronic venous disorders, which according to the CEAP classification are
      those not associated with an identifiable mechanism of venous dysfunction, are
      among the most common in Western populations. Varicose veins without skin changes
      are present in about 20% of the population while active ulcers may be present in
      as many as 0.5%. Primary venous disorders are thought to arise from intrinsic
      structural and biochemical abnormalities of the vein wall. Advanced cases may be
      associated with skin changes and ulceration arising from extravasation of
      macromolecules and red blood cells leading to endothelial cell activation,
      leukocyte diapedesis, and altered tissue remodeling with intense collagen
      deposition. Laboratory evaluation of patients with primary venous disorders
      includes venous duplex ultrasonography performed in the upright position,
      occasionally supplemented with plethysmography and, when deep venous
      reconstruction is contemplated, ascending and descending venography. Primary
      venous disease is most often associated with truncal saphenous insufficiency.
      Although historically treated with stripping of the saphenous vein and
      interruption and removal of major tributary and perforating veins, a variety of
      endovenous techniques are now available to ablate the saphenous veins and have
      generally been demonstrated to be safe and less morbid than traditional
      procedures. Sclerotherapy also has an important role in the management of
      telangiectasias; primary, residual, or recurrent varicosities without connection
      to incompetent venous trunks; and congenital venous malformations. The
      introduction of ultrasound guided foam sclerotherapy has broadened potential
      indications to include treatment of the main saphenous trunks, varicose
      tributaries, and perforating veins. Surgical repair of incompetent deep venous
      valves has been reported to be an effective procedure in nonrandomized series,
      but appropriate case selection is critical to successful outcomes.

PMID- 18068563
TI  - Secondary chronic venous disorders.
AB  - Secondary chronic venous disorders (CVD) usually follow an episode of acute deep
      venous thrombosis (DVT). Most occluded venous segments recanalize over the first
      6 to 12 months after an episode of acute DVT, leading to chronic luminal changes
      and a combination of partial obstruction and reflux. Such morphological changes
      produce venous hypertension with the highest levels of ambulatory venous pressure
      occurring in patients with combined outflow obstruction and distal reflux. The
      clinical manifestations of secondary CVD, including pain, venous claudication,
      edema, skin changes, and ulceration are commonly referred to as the post
      thrombotic syndrome. Such sequelae are best avoided by early and aggressive
      treatment of proximal DVT. The diagnostic evaluation of secondary CVD is similar
      to primary CVD and is based upon duplex ultrasound. However, the definition of
      hemodynamically significant venous stenosis remains obscure and there are no
      reliable tests to confirm the presence of such lesions. Diagnosis depends more on
      anatomic rather than hemodynamic criteria, and IVUS is superior to venography in
      estimating the morphological degree and extent of iliac vein stenosis. The
      fundamental role of compression in the treatment of CVD is well recognized.
      Compliance with compression is essential to heal ulcers and minimize recurrence.
      The efficacy of various adjuncts to ulcer treatment, including complex wound
      dressings and medications have been variable. Although superficial venous surgery
      has not been demonstrated to improve ulcer healing rates, it does decrease ulcer
      recurrence. Deep venous valve reconstruction is performed in only a few
      specialized centers, and the results are better for primary than for secondary
      CVD. Treatment of incompetent perforating veins remains controversial. Although
      artificial venous valves are promising, most early experimental models have
      failed. With respect to venous obstruction, iliocaval angioplasty and stenting
      has emerged as the primary treatment for proximal iliofemoral venous obstruction
      with surgical bypass assuming a secondary role.

PMID- 18068564
TI  - Mapping the future: organizational, clinical, and research priorities in venous
      disease.

PMID- 18068566
TI  - Letters, letters, letters.

PMID- 18068567
TI  - Angle's classification revisited.

PMID- 18068568
TI  - Psychological outcomes.

PMID- 18068569
TI  - Molar class taxonomy.

PMID- 18068570
TI  - Putting research into clinical training.

PMID- 18068571
TI  - Postgraduate education.

PMID- 18068572
TI  - Guest editorials: Three marvelous discussions.

PMID- 18068573
TI  - Making systems better for the benefit of patients.

PMID- 18068575
TI  - Twenty-four month program should stay true to its mission.

PMID- 18068576
TI  - Severe bidentoalveolar protrusion.

PMID- 18068579
TI  - En-masse retraction.

PMID- 18068580
TI  - What would you choose: evidence-based treatment or an exciting, risky
      alternative?

PMID- 18068581
TI  - Sydney diagnostic system.

PMID- 18068582
TI  - Friction and loading.

PMID- 18068583
TI  - Biteplane and bionator appliances.

PMID- 18068585
TI  - Effect of surface treatment and type of cement on the retentive strength of
      orthodontic bands on gold alloy crowns.
AB  - INTRODUCTION: The objective of this study was to evaluate the effect of surface
      treatment of gold alloy crowns and type of cement on the retentive strength of
      orthodontic bands cemented on gold alloy crowns. METHODS: Two hundred eight
      crowns, made of type IV dental gold alloy, were divided into 16 groups based on
      surface treatment (C, no treatment; S, sandblasting; V, V-Primer; and S + V,
      sandblasting and V-Primer) and band cement (resin-modified glass ionomer cement,
      compomer, composite resin, and adhesive resin cement). Bands were cemented on the
      crowns, and tensile loads were applied to measure the retentive strength. Two-way
      analysis of variance (ANOVA) was performed for the retentive strength with the
      factors of surface treatment and type of cement, and the Scheffe multiple
      comparison test was performed as a post-hoc test (alpha = 0.05). RESULTS: The
      retentive strength of the bands was influenced by surface treatment and type of
      cement, and there was significant interaction between the 2 variables based on 2
      way ANOVA (P <.05). Resin-modified glass ionomer cement showed the highest
      retentive strength regardless of surface treatment (>1.26 MPa). CONCLUSIONS:
      Resin-modified glass ionomer cement is the most desirable cement for attaching a
      band to a gold alloy crown. When an adhesive resin cement is used, sandblasting
      of the gold crown is recommended.

PMID- 18068586
TI  - Medicaid expenditures for orthodontic services.
AB  - INTRODUCTION: A survey was conducted in 2006 to determine, on a state-by-state
      basis, the availability of Medicaid-funded orthodontic treatment and, when
      available, the criteria and the funding rates. METHODS: All 50 states were
      contacted by e-mail, telephone, or standard mail to obtain answers to the
      following questions. Does your state provide Medicaid coverage for orthodontic
      services? What qualifications are required to be reimbursed? What is the patient
      cutoff age for reimbursement of services? Is an index used to assess
      malocclusion? If so, which index? What is the primary training of the reviewer?
      How are services reimbursed? Is limited treatment covered? Is interceptive
      treatment covered? What is the total amount reimbursed for 24 months of treatment
      for comprehensive adolescent care? RESULTS: Wide variations of responses were
      received from the states, with no statistical significance between any questions
      based on geographic regions or reimbursement rates, although some trends appeared
      to exist. CONCLUSIONS: This study provides state-by-state details of Medicaid
      programs for orthodontic services and details the extensive variations in
      programs.

PMID- 18068587
TI  - Bacterial adhesion of Streptococcus mutans to orthodontic adhesives with various
      filler-volume fractions.
AB  - INTRODUCTION: The aim of this in-vitro study was to investigate the effect of the
      filler-volume fraction of experimental composite adhesives on the bacterial
      adhesion of Streptococcus mutans. METHODS: Three experimental adhesive groups
      were created: an unfilled urethane-dimethacrylate (UDMA) adhesive, UDMA and a
      filler-volume fraction of 35%, and UDMA and a filler-volume fraction of 70%. The
      embedded filler was silicon dioxide. Additionally, 2 conventional orthodontic
      adhesives, Transbond XT (3M Unitek, Monrovia, Calif) and ConTec Duo (Dentaurum,
      Ispringen, Germany), were examined. S mutans suspensions were incubated with test
      specimens and examined with fluorescence dye and an automated multi-detection
      reader. Moreover, scanning electron micrographs were made to evaluate bacterial
      adhesion on substrata. RESULTS: The experimental adhesives consisting of UDMA and
      various filler-volume fractions of silicon dioxide showed no statistical
      difference in relative fluorescence intensities. Scanning electron micrographs
      demonstrated that greater bacterial colonization and more complex aggregates were
      found on adhesives with high relative fluorescence intensity. Relative
      fluorescence intensity values showed no correlation to the filler-volume fraction
      of the examined adhesives. CONCLUSIONS: The results indicate no relationship
      between the filler-volume fraction of UDMA-based orthodontic adhesives and the
      bacterial adhesion of S mutans.

PMID- 18068588
TI  - Soft-tissue treatment changes in Class II Division 1 malocclusion with and
      without extraction of maxillary premolars.
AB  - INTRODUCTION: In this study, we compared the soft-tissue changes and
      posttreatment status after nonextraction and maxillary premolar extraction
      treatment in patients with Class II Division 1 malocclusion. METHODS: Lateral
      cephalograms of 44 patients, divided into 2 matching groups, were evaluated.
      Group 1 comprised 22 patients (10 boys, 12 girls) treated nonextraction with
      initial and final mean ages of 12.50 and 15.12 years, respectively, and a mean
      treatment time of 2.62 years. This group had an initial mean overjet of 7.97 mm.
      Group 2 consisted of 22 patients (10 boys, 12 girls) treated with extractions of
      2 maxillary premolars with initial and final mean ages of 12.86 and 15.32 years,
      respectively. The mean treatment time was 2.46 years, and the initial mean
      overjet was 8.61 mm. Independent t tests were used to compare the initial and
      final cephalometric status and the treatment changes between the groups. RESULTS:
      According to the results, only 1 soft-tissue variable showed a significant
      treatment change between the groups. However, at the posttreatment stage, there
      were no significant differences between the soft-tissue variables. CONCLUSIONS:
      The protocol including extraction of 2 maxillary premolars provides similar soft
      tissue results as nonextraction treatment of complete Class II malocclusion.

PMID- 18068589
TI  - The effectiveness of Hawley and vacuum-formed retainers: a single-center
      randomized controlled trial.
AB  - INTRODUCTION: Vacuum-formed retainers (VFRs) are often prescribed by
      orthodontists in the British National Health Service (NHS). There is no good
      evidence that VFRs are more effective than Hawley retainers. The aim of this
      study was to compare the clinical effectiveness of Hawley and VFRs over a 6-month
      period of retention. The study design was a randomized clinical trial, performed
      in a single orthodontic practice. METHODS: Eligible patients treated by a
      specialist orthodontist were randomly allocated to either Hawley retainers (n =
      196) or VFRs (n = 201). Two technicians fabricated the retainers to standardized
      designs. A blinded, dentally qualified examiner analyzed the records. Maxillary
      and mandibular dental casts at debond and 6 months into retention were assessed
      for tooth rotations mesial to the first permanent molars, intercanine and
      intermolar widths, and Little's index of irregularity. RESULTS: The results
      showed significantly greater changes in irregularity of the incisors in the
      Hawley group than in the VFR group at 6 months. There were otherwise no
      statistically significant differences. CONCLUSIONS: VFRs are more effective than
      Hawley retainers at holding the correction of the maxillary and mandibular labial
      segments. The median differences were 0.56 mm in the mandibular arch and 0.25 mm
      in the maxillary arch. Although this difference is unlikely to be clinically
      significant in the maxillary arch, it could be considered clinically significant
      in the mandibular arch if located to a single tooth displacement.

PMID- 18068590
TI  - Practice-based comparison of direct and indirect bonding.
AB  - INTRODUCTION: The purpose of this study was to compare bond-failure prevalences,
      numbers of appointments, and treatment times between direct and indirect bracket
      bonding for patients treated in private orthodontic practices. METHODS: A
      convenience sample was collected from 11 orthodontic offices; 5 orthodontists
      (772 patients) used a direct bonding technique, and 6 (596 patients) used an
      indirect technique. Altogether, they examined 29,963 brackets in 1,368 patients.
      Bond failures were recorded by tooth number and by patient during 10 consecutive
      practice days. In addition, the orthodontists reported the treatment time and
      number of visits for each of their 10 most recently completed comprehensive
      patients. RESULTS: The per-patient debond prevalences were 1.17% +/- 3.62% for
      direct bonding and 1.21% +/- 3.81% for indirect bonding (P = .225). Direct-bonded
      patients required a mean (+/- SD) treatment time of 750 +/- 220 days and 22.0 +/-
      7.3 visits; indirect bonding required a mean treatment time of 745 +/- 256 days
      and 22.2 +/- 7.3 visits (P = .691 and P = .653, respectively). CONCLUSIONS: This
      practice-based study showed no difference in the failure rates between direct and
      indirect bonding. Furthermore, total treatment times and numbers of appointments
      did not differ between the 2 techniques.

PMID- 18068591
TI  - Comparison of 2 early treatment protocols for open-bite malocclusions.
AB  - INTRODUCTION: The aim of this study was to compare the effects of the quad
      helix/crib (Q-H/C) appliance and the open-bite bionator (OBB) in patients with
      open-bite malocclusions. The Q-H/C sample included 21 subjects, 15 girls and 6
      boys. The average age for the Q-H/C group before treatment (T1) was 8.4 +/- 1.4
      years, the mean age 1 year after active treatment (T2) was 10.9 +/- 1.6 years,
      and the mean duration of treatment was 2.6 years +/- 9 months. The OBB sample
      contained 20 subjects, 9 girls and 11 boys. The average ages were 8.3 years +/-
      10 months at T1 and 10.8 +/- 1.5 years at T2. The mean duration of observation
      was 2.5 +/- 1.2 years. Lateral cephalograms were analyzed at T1 and T2. The T2 to
      T1 changes in the 2 groups were compared with a nonparametric test for
      independent samples (Mann-Whitney U test). The comparison between the 2 treatment
      protocols for skeletal open-bite malocclusion showed that the Q-H/C appliance is
      significantly more effective than the OBB for the improvement of overbite (+1.9
      mm) in association with extrusion (+1.5 mm) and palatal inclination (+2.9
      degrees) of the maxillary incisors.

PMID- 18068592
TI  - Impact of dental asymmetries on the perception of smile esthetics.
AB  - INTRODUCTION: The purpose of this study was to evaluate the impact of anterior
      tooth asymmetries on the perception of smile esthetics. METHODS: Three pleasant
      female smiles were digitally altered to simulate several degrees of asymmetry of
      the gingival margin of a maxillary central incisor, wear of a maxillary canine
      cusp, and a dental midline shift. Three groups of 50 raters--laypersons,
      orthodontists, and prosthodontists--evaluated the original and the altered images
      and used a visual analog scale to score smile esthetics. RESULTS: The threshold
      of the orthodontists and the prosthodontists for asymmetry of the gingival margin
      of a maxillary central incisor was 0.5 mm; the threshold for laypersons, who were
      less perceptive, was 2.0 mm. Wear of a maxillary canine cusp had no esthetic
      impact for any group of raters. Midline shifts became perceptible when equal to
      or greater than 1.0 mm for orthodontists and 3.0 mm for prosthodontists;
      laypersons saw no alteration. CONCLUSIONS: Laypersons, orthodontists, and
      prosthodontists have different perceptions of attractiveness when evaluating
      gingival margin height of a maxillary central incisor and a dental midline shift.
      These findings might help dental specialists to consider the patient's esthetic
      expectations when planning treatment.

PMID- 18068593
TI  - Malocclusion as a risk factor in the etiology of headaches in children and
      adolescents.
AB  - INTRODUCTION: The purpose of this study was to determine the importance of
      occlusal factors in recurrent headaches in children and adolescents without other
      signs or symptoms of temporomandibular disorders or related craniomandibular
      disorders. METHODS: A sample of 50 children and adolescents, ages 8 to 16, who
      reported headaches was obtained from the University at Buffalo Orthodontic Clinic
      records; a control group of 50 children and adolescents, matched for age and sex,
      was also obtained. Plaster models, made during the routine collection of
      orthodontic records, were used to obtain the following occlusal trait
      measurements: Angle classification, overjet, anterior and posterior crossbite,
      scissors-bite, overbite, open bite, dental midline discrepancy, crowding,
      spacing, and dental development stage. RESULTS: Overbite, overjet, and posterior
      crossbite showed statistically significant associations (chi-square) with
      increased risk for headaches. Logistic regression analysis demonstrated that
      overjet was a significant factor only because of its correlation with overbite
      and posterior crossbite. Overjet was not significant after adjusting for the
      other 2 variables, whereas overbite and posterior crossbite were associated with
      significantly increased risk (>3:1) of headache. The combination of 2 or more of
      these 3 occlusal factors increased the risk of headache even more (8.5:1).
      CONCLUSIONS: Posterior crossbite and overbite > or =5 mm were associated with
      significantly increased risk of headache in children and adolescents.

PMID- 18068594
TI  - Longitudinal study of facial skeletal growth completion in 3 dimensions.
AB  - INTRODUCTION: Previous authors have suggested that transverse facial skeletal
      growth is completed before either anteroposterior or vertical growth and that
      anteroposterior growth is completed before vertical growth. Our purpose in this
      study was to examine this concept. METHODS: Twenty-four subjects (11 male, 13
      female) who had annual lateral and posteroanterior cephalograms up to and
      including age 17 or 18 and again at age 25 or older were identified from the Iowa
      Facial Growth Study. Transverse, anteroposterior, and vertical facial dimensions
      were measured longitudinally into adulthood by using key skeletal landmarks.
      Descriptive statistics were calculated, and nonparametric Wilcoxon signed rank
      tests were performed separately for the sexes to determine the age at which each
      anteroposterior, vertical, and transverse growth variable reached adult size.
      RESULTS: For both sexes, an overlap exists at any age in the amount of growth
      completed for the various measurements in the transverse, anteroposterior, and
      vertical dimensions. Although some transverse measures (cranial width and
      interjugal width) attain adult size before any anteroposterior or vertical ones,
      there is evidence of continued growth for other transverse parameters
      (interzygomatic width and intergonial width). A similar overlap is seen in the
      anteroposterior and vertical dimensions. CONCLUSIONS: A distinct separation, by
      time and dimension, is not seen in the amount of facial growth completed during
      development. Instead, a dramatic spread and an overlap of growth curves are
      observed throughout the developing years.

PMID- 18068595
TI  - Long-term effects of symphyseal distraction and rapid maxillary expansion on
      pharyngeal airway dimensions, tongue, and hyoid position.
AB  - INTRODUCTION: The aim of this study was to evaluate the effects of mandibular
      symphyseal distraction osteogenesis (MSDO) followed by rapid maxillary expansion
      (RME) on the pharyngeal and nasal airway dimensions and the tongue and hyoid
      positions. METHODS: The material consisted of lateral and posteroanterior
      cephalometric radiographs of 13 female and 7 male patients (mean age, 20.0 +/-
      2.3 years). Records were taken before treatment, after distraction (11.4 +/- 2.2
      days after surgery), after RME (94.9 +/- 5.8 days after surgery), and at follow
      up appointments (24.1 +/- 4.2 months after surgery). MSDO was performed with a
      custom-made tooth-and-bone-borne device. RME was performed with an acrylic bonded
      device. The average amounts of mandibular and maxillary expansion were 8.1 +/-
      1.7 and 5.9 +/- 1.0 mm, respectively. RESULTS: Posteroanterior cephalometric
      analysis showed significant transversal width increases between the mandibular
      canines and molars. No significant pharyngeal or transverse nasal airway changes
      occurred with MSDO except for a significant decrease in tongue length. However,
      MSDO followed by RME caused statistically significant but clinically small
      changes in oropharyngeal width (+1.0 mm), tongue length (-2.2 mm), vertical
      airway length (-2.3 mm), and vertical position of the hyoid bone (-1.4 mm), which
      were all stable at the 2-year follow-up. CONCLUSIONS: The results suggest that
      MSDO alone or MSDO followed by RME does not significantly affect the pharyngeal
      airway dimensions or the hyoid position in adults. Any changes caused by these
      procedures might have been counteracted by the reflex mechanisms that protect
      airway potency.

PMID- 18068596
TI  - Surgically assisted rapid maxillary expansion: midfacial and cranial stress
      distribution.
AB  - INTRODUCTION: Our aim in this study was to investigate the stresses in the
      midface and at the cranial base during surgically assisted rapid maxillary
      expansion, to determine whether surgically assisted separation of the maxilla
      from the cranial base can be considered justified and necessary. METHODS: By
      using finite element models, surgically assisted rapid maxillary expansion with
      or without separation of the pterygomaxillary junction was simulated, and the
      stresses at various points in the midface and the cranial base were analyzed. The
      finite element models consisted of more than 50,000 individual elements and
      almost 100,000 nodes. RESULTS: The stresses recorded at the measurement points of
      the midface and the cranial base were usually lower upon separation of the
      pterygomaxillary junction than those measured without this additional surgical
      measure. The stress measured at the optic foramen without separation was 122.4
      MPa, whereas, with separation of the pterygomaxillary junction, it was only 32.7
      MPa. The finite element method proved to be a suitable procedure for comparing
      the biomechanical influences of various therapeutic measures involving a combined
      surgical-orthodontic procedure. The results confirm the effectiveness of an
      additional separation of the pterygomaxillary junction as a protective measure to
      reduce stress to the foramina of the cranial base. CONCLUSIONS: To protect the
      cranial base from undesirable side effects, separation of the pterygomaxillary
      junction appears to be a reasonable and necessary additional measure for
      surgically assisted palatal suture expansion.

PMID- 18068597
TI  - Vertical bone volume in the paramedian palate of adolescents: a computed
      tomography study.
AB  - INTRODUCTION: The paramedian palate (PP) has been used as a host site for
      orthodontic implant anchorage. Available bone and interference of adjacent tooth
      roots must be considered in identifying the most appropriate locations for
      implantations in the PP. METHODS: Cone-beam computed tomography (CBCT) scans
      (NewTom QR-DVT 9000; QR s.r.l., Verona, Italy) were acquired in 183 orthodontic
      patients (ages, 10-19 years). Views of the PP region were reconstructed at
      increments posterior from the incisive foramen, and measurements of bone height
      were made in each reconstruction laterally from the midline to describe the PP.
      RESULTS: At 4 mm posterior to the incisive foramen and 3 mm lateral to the
      midline, 93% of the male and 91% of the female subjects met the criterion for
      implantation. At 8 mm posterior to the incisive foramen and 3 mm lateral to the
      midline, 86% of the male and 58% of the female subjects met the criterion for
      implantation. CONCLUSIONS: The PP contains several valid implant host sites in
      adolescent patients. At 4 mm distal and 3 mm lateral to the incisive foreman,
      93.2% of the boys and 91.9% of the girls had sufficient vertical bone depth to
      host a 3-mm implant with little practical tooth interference. CBCT allows
      accurate assessment of the entire volume of a proposed implant site.

PMID- 18068598
TI  - Adverse patient reactions during orthodontic treatment with fixed appliances.
AB  - INTRODUCTION: Our aims in this study were to assess adverse patient reactions
      during orthodontic treatment with nickel-containing appliances and to investigate
      the need for and the use of nickel-free devices in orthodontic practices in
      Finland and Norway. METHODS: A questionnaire was mailed to orthodontists and
      dentists versed in orthodontics in both countries. They were asked to
      retrospectively assess the number of patients with adverse reactions and to
      describe the reactions, the appliances used, and any implications on treatment.
      Previous history of nickel allergy of patients with adverse reactions, and use of
      and need for nickel-free appliances in clinical practice were also addressed.
      RESULTS: Forty-six percent of the respondents (n = 298) reported at least 1
      adverse patient reaction during the last 5 years. More than half of the reactions
      had implications for the treatment. Finnish respondents observed significantly
      more adverse patient reactions than their Norwegian colleagues, and, in Finland,
      the adverse reactions were most frequently attributed to headgear treatment.
      Using nickel-containing fixed appliances in nickel-allergic patients was more
      common in Finland (77% of the respondents) than in Norway (65%). CONCLUSIONS:
      Nearly half of the dentists regularly working with fixed appliances had observed
      at least 1 adverse patient reaction during treatment. Nickel-containing fixed
      appliances are generally used in most patients-even those with a suspected nickel
      allergy.

PMID- 18068599
TI  - Cluster analysis of tooth size in subjects with normal occlusion.
AB  - INTRODUCTION: Tooth-size studies are important in orthodontics. Our aim in this
      study was to establish normative data on tooth size with a clustering method.
      METHODS: Dental casts of 307 subjects with normal occlusion were examined. In
      these subjects, the tooth-size data sets in the maxilla and the mandible were
      clustered for men and women by using multivariate normal mixture models. This
      analysis clustered the data sets into groups of observations that were cohesive
      and separate from the other groups. The parameters were estimated with
      expectation-maximization procedures, and the number of clusters was selected via
      the Bayesian information criterion. RESULTS: Seven heterogeneous clusters in men
      and 4 clusters in women were identified. This study indicated that, in normal
      occlusion, tooth sizes are variable. These heterogeneities in the normal
      occlusion group seem to have contributed to the variability found in normative
      data. CONCLUSIONS: The method used in this study seems to provide a more
      substantive design for artificial teeth and add an additional dimension in the
      process of diagnosis of patients. Further applications seem possible in dental
      anthropometry by simultaneously dealing with the full dentition as a data set.

PMID- 18068600
TI  - Comparing subjective and objective measures of headgear compliance.
AB  - INTRODUCTION: Many studies have used subjective measures to examine patient
      compliance during orthodontic treatment. Objective measurement of compliance has
      been confined to only a few studies that used electronic timing devices built
      into removable appliances. Our aim in this study was to compare subjective and
      objective methods of measuring compliance with headgear wear. It was hypothesized
      that orthodontists, patients, and patients' parents overestimate compliance and
      report more wearing hours than the headgear timers indicate. Also, relationships
      between sex, age, treatment time, and headgear compliance were explored. METHODS:
      A headgear timer device and 3 questionnaires were developed to assess compliance.
      The subjects were unaware that their headgear use was being measured. RESULTS:
      Significant differences between the estimates of orthodontists, patients,
      parents, and headgear timer scores were found. Also, there were differences
      regarding age and treatment time. CONCLUSIONS: Subjective measures might result
      in overestimation of compliance. This suggests that the use of an objective
      instrument to measure headgear compliance should be continued in future studies.

PMID- 18068601
TI  - A follow-up study of dental and skeletal changes associated with mandibular
      advancement splint use in obstructive sleep apnea.
AB  - INTRODUCTION: Mandibular advancement splints (MAS) are a recognized therapeutic
      option in the treatment of obstructive sleep apnea (OSA). This study aimed to
      investigate side effects and possible changes in the dentofacial complex
      associated with long term use of MAS. METHODS: The sample included 64 patients
      with OSA who had been using MAS on average for 25.1 +/- 11.8 months (range, 10.7
      64.5 months). A specifically designed questionnaire was used to investigate the
      patients' self-assessment of the side effects of wearing MAS; cephalometric
      analyses and dental cast measurements were conducted to identify objectively
      dental and skeletal changes caused by MAS over time. RESULTS: The most commonly
      reported side effects were jaw discomfort, tooth tenderness, excessive
      salivation, and dry mouth. Subjectively, snoring improved in 56 patients (88%),
      and daytime sleepiness (Epworth sleepiness scale) scores significantly decreased
      from pretreatment to follow-up (11.4-7.1, P <.001). Small subjective occlusal
      changes were experienced by 8 patients (12.5%). Reductions in overbite (-0.3 +/-
      0.08 mm, P <.01) and overjet (-0.2 +/- 0.06 mm, P <.05) were found, and
      cephalometric analysis showed statistically significant but clinically
      insignificant changes limited to anterior movement of the mandibular incisors
      (0.5 +/- 0.12 mm, P <.001). CONCLUSIONS: Side effects of MAS use over long
      periods are common but mild and well tolerated by most patients, and dentofacial
      changes are negligible.

PMID- 18068602
TI  - Quantitative determination of adhesion patterns of cariogenic streptococci to
      various orthodontic brackets.
AB  - INTRODUCTION: Information about the adhesion of cariogenic streptococci to
      orthodontic brackets can help to determine a means for preventing enamel
      demineralization. The purpose of this study was to investigate the adhesion
      levels of 4 cariogenic streptococci strains to various orthodontic brackets with
      respect to bracket type, bacterial strain, incubation time, and saliva coating.
      METHODS: Five bracket types (monocrystalline sapphire, polycrystalline alumina,
      stainless steel, plastic, and titanium) were incubated with unstimulated whole
      saliva or phosphate-buffered saline solution for 2 hours. Binding assays were
      then performed by incubating tritium-labeled streptococci with the brackets for 3
      or 6 hours. RESULTS: Each cariogenic streptococci strain showed a characteristic
      adhesion pattern. The adhesion amounts were highest in the plastic brackets and
      lowest in the monocrystalline sapphire brackets. Longer incubation time generally
      increased bacterial adhesion. Saliva coating did not significantly influence the
      adhesion of S mutans strains, but it had a significant effect on the adhesion of
      S sobrinus strains. However, saliva coating tended to decrease the adhesion of
      cariogenic streptococci with the longer incubation time compared with the
      noncoated control. CONCLUSIONS: This study suggests that cariogenic streptococci
      have various patterns of adhesion according to the bracket type.

PMID- 18068603
TI  - Treatment outcomes in a graduate orthodontic clinic for cases defined by the
      American Board of Orthodontics malocclusion categories.
AB  - INTRODUCTION: The American Board of Orthodontics (ABO) discrepancy index (DI)
      quantifies the severity of a malocclusion. The ABO objective grading system (OGS)
      assesses the quality of orthodontic finishing. Indiana University's comprehensive
      clinical assessment (CCA) supplements the OGS to provide an instrument to
      determine clinical outcomes. The purposes of this article were to (1) determine
      whether treatment outcome is related to the type of malocclusion as defined by
      the ABO classification, (2) determine the fraction of finished orthodontic cases
      in the graduate orthodontics clinic that are within the ABO standards for passing
      the phase III clinical examination, (3) evaluate the contribution of each
      component of the OGS and the CCA to the total OGS and CCA scores, (4) determine
      the percentage of finished cases that meet the ABO case category specifications,
      and (5) identify problem areas to improve the quality of treatment for
      challenging malocclusions. METHODS: Three hundred eighty-two cases that satisfied
      requirements for 8 of the ABO's malocclusion categories were selected from 989
      consecutively finished cases from 1998 through 2003. They were evaluated by using
      the OGS, the CCA, and the DI. RESULTS: The average OGS score was 32.64, the
      average CCA score was 5.62, and the average DI score was 20.94. There was no
      significant difference in the OGS and the CCA scores among the categories.
      Categories 2, 5, 7, and 8 had a DI score that was significantly higher than the
      average for the entire sample. The OGS and CCA scores were positively correlated
      with the DI score, meaning that complex malocclusions are challenging to finish
      well. The most points lost for the OGS and the CCA were for occlusal contacts and
      treatment efficiency (length of treatment relative to the result), respectively.
      The fewest points lost were for interproximal contacts and vertical control,
      respectively. Furthermore, prematurely terminated cases (early debonds) had
      longer treatment times and higher (worse) OGS and CCA scores. CONCLUSIONS: This
      study demonstrates problems in treating complex malocclusions in a graduate
      orthodontics program and suggests methods for increasing the quality of clinical
      outcomes.

PMID- 18068604
TI  - Comparison of measurements from photographed lateral cephalograms and scanned
      cephalograms.
AB  - INTRODUCTION: In this study, we investigated whether a digital photograph of a
      lateral cephalometric radiograph can produce measurements as accurate as those
      from a digital image created with a flatbed scanner. METHODS: Twenty pretreatment
      lateral cephalograms were randomly selected from the patient files at
      Chesterfield Royal Hospital. Each radiograph was photographed with a digital
      camera and scanned with a flatbed scanner. Both images were digitized with
      imaging software (Dolphin, Chatsworth, Calif). Common cephalometric analyses were
      performed on both images, and the measurements were recorded. The paired Student
      t test was used to test for statistically significant differences between the
      measurements of the images. RESULTS: Angular measurements were not significantly
      different between the photographed and scanned images, but linear measurements
      were. CONCLUSIONS: It is acceptable to use digital photographs of cephalograms if
      angular measurements are primarily required. However, these images might not be
      acceptable if linear measurements are needed.

PMID- 18068605
TI  - Changes in the stiffness of the ligating mechanism in retrieved active self
      ligating brackets.
AB  - INTRODUCTION: The purpose of this study was to investigate the effect of
      intraoral aging on the force applied during engagement of a wire into the slot of
      active self-ligating brackets. METHODS: Two types of brackets were used: Speed
      (Speed System Orthodontics, Cambridge, Ontario, Canada) and In Ovation-R (GAC,
      Bohemia, NY). Ten as-received and 10 retrieved maxillary incisor brackets
      collected after full treatment for at least 15 months (range, 15-19 months) were
      included in each bracket group. The brackets were mounted on the orthodontic
      measurement and simulation system, and the spring was subjected to tensile
      stress, which induced deformation of up to 1.5 mm, with a custom-made jig and
      laboratory configuration at body temperature. On the loading portion of the
      loading-unloading curve of clips, the slope was fitted a first-degree equation
      curve, to determine the stiffness/deflection rate of the clip. The results of
      slopes and ranges were analyzed with a 2-sample t test at the .05 level of
      significance, with aging as the discriminating variable. RESULTS: No difference
      was found between as-received and used brackets with respect to force exerted by
      the spring in 1 bracket group, whereas the other group showed extensive
      relaxation after use; neither group had permanent deformation. The consistency of
      the initial force levels varied significantly in each bracket group. CONCLUSIONS:
      The initial force levels and the effect of intraoral conditions on the stiffness
      of the clip seem to vary between products, with potential implications for the
      archwire engagement into the bracket slot and associated mechanotherapy.

PMID- 18068606
TI  - Unexpected complications of bonded mandibular lingual retainers.
AB  - INTRODUCTION: The flexible spiral wire (FSW) retainer is the most frequently used
      type of fixed retainer bonded on all 6 anterior teeth. Our aim in this article
      was to demonstrate unexpected posttreatment changes in the labiolingual position
      of the mandibular anterior teeth associated with the use of FSW retainers.
      METHODS: During a 3-year period, patients attending the postgraduate orthodontic
      clinic of the Department of Orthodontics and Oral Biology, Radboud University
      Nijmegen Medical Center, Nijmegen, The Netherlands, for regular, posttreatment
      follow-up appointments were screened for unexpected posttreatment changes in the
      mandibular anterior region. RESULTS: Twenty-one patients with FSW retainers
      bonded on all 6 mandibular anterior teeth presented unexpected posttreatment
      changes in that region. Almost half of these patients were assessed as needing
      retreatment. Two patients are presented to illustrate the 2 distinct patterns of
      posttreatment changes: torque difference between 2 adjacent mandibular incisors
      and increased buccal inclination and movement of one mandibular canine.
      CONCLUSIONS: FSW retainers bonded on the 6 mandibular anterior teeth might cause
      unexpected movements of anterior teeth to such an extent that retreatment is
      necessary. Clinicians should consider this possibility when planning the
      retention strategy.

PMID- 18068607
TI  - Scissors-bite correction on second molar with a dragon helix appliance.
AB  - Many efforts have been made to correct scissors-bite and establish proper molar
      interdigitation for prosthetic or orthodontic treatment. The critical procedures
      for scissors-bite correction are intruding and palatally tipping the involved
      tooth when it is both extruded and buccally flared. Conventional approaches give
      rise to problems such as repetitive bonding failure and loss of anchorage. A
      newly designed spring, the dragon helix appliance, is used with an indirect
      skeletal anchorage system to correct scissors-bite. This spring provides
      effective tooth movement and the convenience of a simple and small design. We
      report a successful treatment with the dragon helix.

PMID- 18068608
TI  - Mandibular distraction osteogenesis for treatment of extreme mandibular
      hypoplasia.
AB  - Distraction osteogenesis is an important option for the treatment of mandibular
      hypoplasia. This case report describes the treatment of a girl with mandibular
      hypoplasia and sleep apnea. She had a tracheostomy, followed by orthodontic
      treatment, including extraoral mandibular distraction osteogenesis to open the
      airway. Follow-up records 4 year 8 months after the distraction osteogenesis are
      presented.

PMID- 18068609
TI  - A model for digital archiving of radiographs into a searchable database.
AB  - Digital images are routinely used in orthodontic practices today. Many systems
      and formats are available for producing, storing, retrieving, viewing, and
      sharing these images. The digital imaging and communication in medicine (DICOM)
      standard is designed to ensure that these systems and formats are compatible, so
      that an image produced in a small private practice today can be viewed next year
      in a large hospital. The purpose of this article is to describe a method for
      laser scanning and digitization of analog (film) radiographs that meets DICOM
      standards and allows for web-based archiving, searching, and retrieval.

PMID- 18068610
TI  - A future for systems and computational neuroscience in France?
AB  - This special issue of the Journal of Physiology, Paris, is an outcome of
      NeuroComp'06, the first French conference in Computational Neuroscience. The
      preparation for this conference, held at Pont-a-Mousson in October 2006, was
      accompanied by a survey which has resulted in an up-to-date inventory of human
      resources and labs in France concerned with this emerging new field of research
      (see team directory in http://neurocomp.risc.cnrs.fr/). This thematic JPP issue
      gathers some of the key scientific presentations made on the occasion of this
      first interdisciplinary meeting, which should soon become recognized as a yearly
      national conference representative of a new scientific community. The present
      introductory paper presents the general scientific context of the conference and
      reviews some of the historical and conceptual foundations of Systems and
      Computational Neuroscience in France.

PMID- 18068611
TI  - Clinical, neurohormonal, and inflammatory markers and overall prognostic role of
      chronic obstructive pulmonary disease in patients with heart failure: data from
      the Val-HeFT heart failure trial.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) and heart failure are
      major causes of death and disability. Because little information is available
      about the population of patients with both syndromes, we assessed the
      characteristics and the independent contribution of COPD to outcomes in patients
      with stable chronic heart failure. METHODS: The clinical, neurohormonal, and
      echocardiographic characteristics of the 5010 patients enrolled in the Valsartan
      Heart Failure Trial were compared in patients with or without COPD. The
      prognostic value of COPD was tested by multivariate Cox proportional hazard
      models. RESULTS: Patients with COPD were older, more symptomatic, and less likely
      to be receiving beta-blocker therapy, and had a higher mortality (27.4% vs.
      18.4%, P < .0001). Echocardiographic parameters were not different, and brain
      natriuretic peptide was only minimally increased. Norepinephrine, inflammatory
      markers, cardiac troponin T, and creatinine values were significantly higher.
      After adjustment, COPD no longer predicted all-cause mortality but remained
      predictive of noncardiovascular mortality (hazard ratio 2.50; 95% confidence
      interval: 1.58-3.96; P < .0001) and hospitalizations, especially
      noncardiovascular (hazard ratio 1.71; 95% confidence interval; 1.43-2.06; P <
      .0001). CONCLUSIONS: Patients with COPD are more symptomatic and have worse
      outcomes that are not explained by poorer left ventricular function. After
      adjustment for demographic, clinical, biohumoral, and treatment variables, COPD
      is a weak predictor of all-cause mortality but a strong predictor of
      noncardiovascular events. Awareness and optimized treatment of heart failure and
      COPD may reduce the clinical burden of these patients.

PMID- 18068612
TI  - Predictors of cardiac events after cardiac resynchronization therapy with tissue
      Doppler-derived parameters.
AB  - BACKGROUND: To evaluate the prognostic value of tissue Doppler imaging (TDI)
      derived parameters (E/E' ratio and Tei index) in heart failure (HF) patients who
      underwent cardiac resynchronization therapy (CRT). METHODS AND RESULTS: The study
      comprised 74 consecutive HF patients (mean age 60 +/- 11 years) who underwent
      CRT. Echocardiography including TDI measurements was performed in all patients at
      baseline and 3 months after CRT. During a median follow-up period of 720 days
      (range 210 to 1020 days), 21 patients (28%) had events (8 deaths, and
      hospitalization for HF in the remaining 13). From the baseline clinical and
      echocardiography data, univariable Cox-regressions analysis revealed that only
      diabetes (hazard ratio [HR] 3.703, P < .01), E/A ratio (HR 3.492, P < .001), and
      E/E' ratio (HR 1.130, P < .001) were predictors for cardiac events. From the 3
      month follow-up data, the E/A ratio (HR 2.988, P < .005), E/E' ratio (HR 1.170, P
      < .001), left ventricular ejection fraction (HR 0.835, P < .01), deceleration
      time (HR 0.977, P < .05), and the Tei index (HR 15.784, P < .001) were predictors
      for cardiac events. After multivariable analysis, only diabetes (HR 5.544, P <
      .05), the 3-month E/E' ratio (HR 1.229, P < .001), and change in Tei index (HR
      32.174, P < .001) were independent predictors for cardiac events. Patients with a
      high baseline and 3-month follow-up E/E' ratio had an 88% cardiac event rate.
      CONCLUSIONS: The Tei index and E/E' ratio are independent predictors of poor
      response and cardiac events after CRT.

PMID- 18068613
TI  - Losartan improves heart rate variability and heart rate turbulence in heart
      failure due to ischemic cardiomyopathy.
AB  - BACKGROUND: Heart rate variability (HRV) and heart rate turbulence are known to
      be disturbed and associated with excess mortality in heart failure. The aim of
      this study was to investigate whether losartan, when added on top of beta-blocker
      and angiotensin-converting enzyme inhibitor (ACEI) therapy, could improve these
      indices in patients with systolic heart failure. METHODS AND RESULTS: Seventy
      seven patients (mean age 60.4 +/- 8.0, 80.5% male) with ischemic cardiomyopathy
      (mean ejection fraction 34.5 +/- 4.4%) and New York Heart Association Class II
      III heart failure symptoms, already receiving a beta-blocker and an ACEI, were
      randomly assigned to either open-label losartan (losartan group) or no additional
      drug (control group) in a 2:1 ratio and the patients were followed for 12 weeks.
      The HRV and heart rate turbulence indices were calculated from 24-hour Holter
      recordings both at the beginning and at the end of follow-up. The baseline
      clinical characteristics, HRV, and heart rate turbulence indices were similar in
      the 2 groups. At 12 weeks of follow-up, all HRV parameters except pNN50 increased
      (SDNN: 113.2 +/- 34.2 versus 127.8 +/- 24.1, P = .001; SDANN: 101.5 +/- 31.7
      versus 115.2 +/- 22.0, P = .001; triangular index: 29.9 +/- 11.1 versus 34.2 +/-
      7.9, P = .008; RMSSD: 29.1 +/- 20.2 versus 34.3 +/- 23.0, P = .009; NN50: 5015.3
      +/- 5554.9 versus 6446.7 +/- 6101.1, P = .024; NN50: 5.65 +/- 6.41 versus 7.24 +/
      6.99, P = .089; SDNNi: 45.1 +/- 13.3 versus 50.3 +/- 14.5, P = .004), turbulence
      onset decreased (-0. 61 +/- 1.70 versus -1.24 +/- 1.31, P = .003) and turbulence
      slope increased (4.107 +/- 3.881 versus 5.940 +/- 4.281, P = .004) significantly
      in the losartan group as compared with controls. CONCLUSIONS: A 12-week-long
      losartan therapy significantly improved HRV and heart rate turbulence in patients
      with Class II-III heart failure and ischemic cardiomyopathy already on beta
      blockers and ACEI.

PMID- 18068614
TI  - Depression is a major determinant of quality of life in patients with chronic
      systolic heart failure in general practice.
AB  - BACKGROUND: Quality of life (QoL) is severely restricted in patients with chronic
      heart failure (CHF). Patients frequently suffer from depressive comorbidity. It
      is not clear, to what extent sociodemographic variables, heart failure severity,
      somatic comorbidities and depression determine QoL of patients with CHF in
      primary care. METHODS AND RESULTS: In a cross-sectional analysis, 167 patients,
      68.2 +/- 10.1 years old, 68.9% male, New York Heart Association (NYHA) functional
      class II-IV, Left ventricular ejection fraction (LVEF) < or = 40%, were recruited
      in their general practitioner's practices. Heart failure severity was assessed
      with echocardiography and N-terminal brain natriuretic peptide (NT-proBNP);
      multimorbidity was assessed with the Cumulative Illness Rating Scale (CIRS-G).
      QoL was measured with the Short Form 36 Health Survey (SF-36) and depression with
      the depression module of the Patient Health Questionnaire (PHQ-9). Significant
      correlations with all SF-36 subscales were only found for the CIRS-G (r = -0.18
      to -0.36; P < .05) and the PHQ-9 (r = -0.26 to -0.75; P < .01). In multivariate
      forward regression analyses, the PHQ-9 summary score explained the most part of
      QoL variance in all of the SF-36 subscales (r2 = 0.17-0.56). LVEF and NT-proBNP
      did not have significant influence on QoL. CONCLUSIONS: Depression is a major
      determinant of quality of life in patients with chronic systolic heart failure,
      whereas somatic measures of heart failure severity such as NT-proBNP and LVEF do
      not contribute to quality of life. Correct diagnosis and treatment of depressive
      comorbidity in heart failure patients is essential.

PMID- 18068615
TI  - Six-month aerobic exercise training ameliorates central sleep apnea in patients
      with chronic heart failure.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is common in patients with heart
      failure and carries an independent risk for poor long-term prognosis. We aimed to
      study the effects of supervised, aerobic exercise training for 6 months on SDB in
      patients with chronic heart failure. METHODS AND RESULTS: We enrolled 18 patients
      having both systolic dysfunction (left ventricular ejection fraction <45%) and
      SDB (apnea-hypopnea index [AHI] >10). The exercise group comprised 10 patients
      who participated in our cardiac rehabilitation program for 6 months, and the
      remaining 8 patients served as control. AHI (median [interquartile range]) was
      unchanged in the control group patients at 6-month intervals (30.4 [19.9-36.3]
      versus 36.6 [8.6-39.4], NS). In contrast, AHI was significantly decreased in the
      exercise group from 24.9 [19.2-37.1] to 8.8 [5.3-10.1] (P < .01). In the exercise
      group, the numbers of central sleep apnea per night was significantly decreased
      (152 [124-244] versus 50 [24-67], P < .01) after exercise training, but those of
      obstructive apnea/hypopnea were unchanged (42 [7-94] versus 18 [7-54], NS). In
      addition, exercise training significantly increased peak oxygen consumption and
      decreased minute ventilation to carbon dioxide production slope (both P < .01).
      CONCLUSIONS: Six-month, aerobic exercise training increased exercise capacity and
      improved central sleep apnea in patients with chronic heart failure from systolic
      dysfunction.

PMID- 18068616
TI  - Prognostic value of extravascular lung water assessed with ultrasound lung comets
      by chest sonography in patients with dyspnea and/or chest pain.
AB  - BACKGROUND: Ultrasound lung comets (ULCs) consist of multiple comet tails
      originating from water-thickened interlobular septa. They are a new echographic
      tool to assess the pathologic increase in extravascular lung water, which is a
      possible harbinger of impending acute heart failure. The objective was to assess
      the prognostic value of ULCs in patients with dyspnea and/or chest pain syndrome
      at hospital admission. METHODS AND RESULTS: A total of 290 consecutive in
      hospital patients (aged 68 +/- 13 years) admitted for dyspnea and/or chest pain
      syndrome were evaluated on admission with a comprehensive two-dimensional and
      Doppler echocardiographic evaluation and chest sonography with ULC assessment. A
      patient ULC score was obtained by summing the number of comets from each of the
      scanning spaces in the anterior right and left hemithoraxes, from the second to
      fifth intercostal spaces. All patients were followed up for a median period of 16
      months (interquartile range: 2.8-29.1 months). During the follow-up, 62 events
      occurred: 19 cardiac deaths, 3 nonfatal myocardial infarctions, 20 acute heart
      failures requiring hospitalization, and 20 noncardiac deaths. The 16-month event
      free survival was highest in patients with no ULCs and lowest in patients with
      severe (>30) ULCs at entry (70% vs 19%, P = .0007). At univariate analysis, ULCs
      (hazard ratio [HR] 2.349; confidence interval [CI] 1.364-4.044) were more
      powerful predictors than other echocardiographic variables of recognized
      prognostic value, including ejection fraction (HR 0.974; 95% CI 0.958-0.99) and
      wall motion score index (HR 1.628; CI 1.15-2.304). On multivariable analysis,
      ULCs provided additional prognostic information (HR 1.9; 95% CI 1.1-3.4) on
      diabetes (HR 2.05; 95% CI 1.2-3.5) and New York Heart Association class (HR 1.3;
      95% CI 1.0-1.6). CONCLUSION: ULCs are a simple user-friendly, radiation-free
      bedside sign of extravascular lung water. They provide useful information for the
      prognostic stratification of patients with dyspnea and/or chest pain syndrome.

PMID- 18068617
TI  - Prognostic value of pharmacologic stress echocardiography in patients with
      idiopathic dilated cardiomyopathy: a prospective, head-to-head comparison between
      dipyridamole and dobutamine test.
AB  - BACKGROUND: Inotropic reserve identified by dobutamine or dipyridamole stress
      echocardiography is associated with a better outcome in patients with idiopathic
      dilated cardiomyopathy (DCM), although the relative prognostic value of each
      remains unsettled. The purpose of the present study was to assess the relative
      prognostic value of dobutamine versus dipyridamole stress echocardiography for
      the prediction of all-cause death in patients with idiopathic DCM. METHODS AND
      RESULTS: Eighty-seven patients (63 were male, aged 54 +/- 12 years) with DCM and
      an ejection fraction less than 35% underwent both dipyridamole and dobutamine
      stress echocardiography on different days and in a random order. In all patients,
      wall motion score index and ejection fraction were evaluated at baseline and peak
      stress. All patients were followed up for an average of 52 months. All-cause
      death was identified as the prognostic end point. During the follow-up, 26 all
      cause deaths occurred (29.8%). On multivariate analysis, either dobutamine
      echocardiography (relative risk 0.299; P = .02; 95% confidence interval 0.084
      0.835) or dipyridamole echocardiography (relative risk 0.161; P < .00; 95%
      confidence interval 0.07-0.394) added significantly to a prognostic model based
      on clinical and resting echocardiographic variables. Survival was 83% in patients
      with dobutamine and 84% in patients with dipyridamole-induced contractile
      reserve. CONCLUSIONS: Dobutamine and dipyridamole stress echocardiography have
      similar feasibility and prognostic accuracy in DCM risk stratification.

PMID- 18068618
TI  - Plasma MMP-2, MMP-9 and N-BNP in long-term survivors following complicated
      myocardial infarction: relation to cardiac magnetic resonance imaging measures of
      left ventricular structure and function.
AB  - BACKGROUND: Altered activity of the matrix metalloproteinases (MMP-2 and -9), has
      been implicated in the left ventricular (LV) remodeling process occurring after
      myocardial infarction (MI). In the acute phase, a relation between plasma MMP-9
      levels and parameters of LV dysfunction has been demonstrated. The relationship
      in long-term survivors has not been investigated. We studied the relationships of
      these biochemical markers, and N-terminal pro-B-type natriuretic peptide (N-BNP),
      with measures of long-term LV remodeling. METHODS AND RESULTS: Plasma levels of N
      BNP, MMP-2, and MMP-9 were measured at randomization, 1 month, 1 year, and > 4
      years after complicated AMI. Contrast-enhanced cardiac magnetic resonance (CMR)
      was performed at 4.4 (+/-0.4) years in 52 clinically stable long-term survivors
      of the index AMI. We assessed the relationships of plasma N-BNP, MMP-2, and MMP-9
      with myocardial scarring, and measures of long-term LV remodeling. Compared with
      a reference population, N-BNP and MMP-9 levels were increased at all time points
      from the acute phase until > 4 years after MI. Plasma N-BNP and MMP-9 correlated
      only in the subacute phase (randomization, mean 3.3 days after MI) days after
      acute MI (r = 0.38, P = .006). At CMR assessment > or = 4 years, log MMP-9 level
      was inversely related to LV ejection fraction (P = .002) and nonscarred
      myocardial mass (P = .008). This relationship was independent of MMP-2. Log N-BNP
      was related to end diastolic volume index (P = .0002). There was no correlation
      between log MMP-9 and LV volumes. CONCLUSION: There is a time-dependent
      relationship between plasma N-BNP and MMP-9 levels, these peptides correlating
      only in the acute phase after MI. In long-term follow-up, plasma MMP-9 and N-BNP
      levels were related to different parameters of LV remodeling. These findings
      suggest that in long-term survivors of complicated MI, different mechanisms
      modulate plasma levels of MMP-9 and N-BNP.

PMID- 18068619
TI  - Increased S100B serum levels in dilated cardiomyopathy patients.
AB  - BACKGROUND: The S100B protein is considered a biochemical marker for brain
      injuries. However, our group demonstrated that the isolated rat heart releases
      S100B. In this study, we investigated the serum levels of S100B in dilated
      cardiomyopathy (DCM) patients to evaluate its levels in heart disease. METHODS
      AND RESULTS: We selected DCM patients, excluding any condition that could
      influence S100B serum levels. Control individuals were sex and age matched. Both
      groups were submitted to clinical evaluation and echocardiography. We measured
      the S100B and NT-proBNP serum levels (expressed as median [interquartile range]).
      NT-proBNP levels in patients group (1462 pg/mL [426-3591]) were higher than in
      controls (35 pg/mL [29-55]), P < .001. S100B serum levels were higher in patients
      group (0.051 microg/L [0.022-0.144]) than in controls (0.017 microg/L [0.003
      0.036]), P = .009. Additionally, we found a positive correlation between S100B
      and NT-proBNP serum levels only in patients group (Spearman's coefficient r =
      0.534; P = .013). CONCLUSIONS: Although we cannot rule out the influence of S100B
      from brain, the positive correlation between S100B and NT-proBNP levels in DCM
      patients points to the myocardium as the main source for the rise in S100B serum
      levels.

PMID- 18068620
TI  - Prognosis of hospitalized new-onset systolic heart failure in Indo-Asians--a
      lethal problem.
AB  - BACKGROUND: Systolic heart failure (SHF), particularly when requiring hospital
      admission carries a poor prognosis. There is a paucity of data in Indo-Asians on
      outcomes of SHF, among whom the burden of cardiovascular disease is consistently
      rising. The purpose of this study was to determine the frequency and predictors
      of mortality and morbidity amongst patients admitted with new-onset SHF at a
      tertiary care hospital in Pakistan. METHODS AND RESULTS: Hospital charts of 196
      patients with a diagnosis of new or recent onset (<3 months) SHF (ejection
      fraction [EF] <40%) were reviewed. Patients who died during the admission, those
      with life-limiting concomitant disease, and those without follow-up were
      excluded. Survival was calculated according to the Kaplan-Meier method. Hazards
      ratios (HR) and 95% confidence intervals (CI) were calculated using Cox's
      regression model. Mean age (SD) was 61 (12.8) years. Majority (77%) had a prior
      ischemic heart disease. Mean EF (SD) was 25% (8.7). Median follow-up period was
      379 days. Fifty-four (27.5%) patients died (at least 12 [22.2%] sudden deaths)
      and 102 (52%) experienced combined event of death or repeat hospitalization for
      SHF. Factors independently associated with death included (HR [95% CI]), serum
      sodium (0.94 [0.90-0.97]), admission pulse (1.02 [1.01-1.04]), systolic blood
      pressure (0.98 [0.97-0.99]), and severe mitral regurgitation (1.90 [1.03-3.48]).
      CONCLUSIONS: Admission for new or recent onset SHF predicts a grave 1-year
      prognosis in Indo-Asians. Measures to prevent ischemic heart disease and its
      sequelae are essential because developing nations simply cannot afford to treat
      and manage heart failure.

PMID- 18068621
TI  - Heart failure in diabetes and related conditions.
AB  - BACKGROUND: Despite advances in therapy for congestive heart failure (CHF),
      mortality remains 40% to 80% higher for diabetics with CHF than nondiabetics.
      Diabetes prevalence is increasing worldwide with prevalence of diabetes among
      patients with CHF increasing at an even faster pace. METHODS AND RESULTS:
      Although multiple mechanisms are responsible for development of CHF in diabetes,
      ischemic heart disease plays a major role. In the foreseeable future, physicians
      will have to deal with increasing numbers of subjects with diabetes, coronary
      disease, and heart failure. Several recent developments in the field of heart
      failure have revolutionized the way patients are treated for CHF with
      improvements in quality of life and mortality. Although long-term prospective
      studies specifically addressing heart failure in diabetes are lacking,
      extrapolation of data from recent large trials has shed light on management of
      CHF in diabetes. CONCLUSIONS: This review summarizes new developments in the
      field of CHF among subjects with diabetes, metabolic syndrome, and obesity.

PMID- 18068622
TI  - In vivo hepatocyte growth factor gene transfer reduces myocardial ischemia
      reperfusion injury through its multiple actions.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is reported to protect the heart
      against ischemia-reperfusion injury. However, whether in vivo adenovirus-mediated
      HGF gene transfer before ischemia is protective against ischemia-reperfusion and
      its precise mechanisms are still unknown. METHODS AND RESULTS: By using a rabbit
      model of ischemia-reperfusion injury, we demonstrate that HGF gene transfer is
      cardioprotective through its multiple beneficial actions, such as angiogenesis,
      Bcl-2 overexpression, and decreasing hydroxyl radicals, deoxyuride-5'
      triphosphate biotin nick end labeling (TUNEL)-positive myocytes, and fibrotic
      area. After HGF gene transfer, the rabbits underwent 30 minutes of coronary
      occlusion and 30 minutes, 4 hours, 48 hours, and 14 days of reperfusion. The
      infarct size at 48 hours of reperfusion was significantly reduced in the HGF
      group (13.4% +/- 2.3%) compared with that in the LacZ group (36.5% +/- 2.0%) and
      saline group (40.3% +/- 3.2%). At 14 days of reperfusion, HGF gene transfer
      improved left ventricular ejection fraction and fractional shortening, reduced
      the fibrotic area, and increased the capillary density in the risk area. At 4
      hours of reperfusion, Bcl-2 protein was overexpressed and the incidence of TUNEL
      positive myocytes was significantly decreased in the risk area in the HGF group
      compared with the LacZ and saline groups. The myocardial interstitial 2,5
      dihydroxybenzoic acid level, an indicator of hydroxyl radical, increased during
      30 minutes of ischemia and 30 minutes of reperfusion in the LacZ and saline
      groups, and was significantly inhibited in the HGF group. CONCLUSION: HGF gene
      therapy may be a novel therapeutic strategy against unstable angina pectoris or
      severe angina pectoris, which may progress to acute myocardial infarction.

PMID- 18068624
TI  - The UK and Denmark are still the countries with low all-cancer survival in
      Europe.

PMID- 18068623
TI  - Dietary supplementation with vitamin E ameliorates cardiac failure in type I
      diabetic cardiomyopathy by suppressing myocardial generation of 8-iso
      prostaglandin F2alpha and oxidized glutathione.
AB  - BACKGROUND: Diabetic cardiomyopathy has been documented as an underlying cause of
      heart failure in diabetic patients. Although oxidative stress has been implicated
      in diabetic cardiomyopathy, much of the current evidence lacks specificity.
      Furthermore, studies investigating antioxidant protection with vitamin E in this
      unique cardiac phenomenon have yet to be performed. In the present study, we
      sought to determine whether vitamin E supplementation can confer cardioprotective
      effects against diabetic cardiomyopathy in relation to specific and quantitative
      markers of myocardial oxidative stress. METHODS AND RESULTS: Diabetes was induced
      in rats by a single injection of streptozotocin. Animals were fed either a basal
      diet or a diet enriched with 2000 IU of vitamin E per kilogram beginning
      immediately after induction of diabetes and continued for 8 weeks. Rats were
      examined for diabetic cardiomyopathy by left ventricular (LV) hemodynamic
      analysis. Myocardial oxidative stress was assessed by measuring the formation of
      8-iso-prostaglandin F2alpha and oxidized glutathione. In the unsupplemented
      streptozotocin-diabetic rats, LV systolic pressure, rate of pressure increase
      (+dP/dt), and rate of pressure decay (-dP/dt) were depressed, whereas LV end
      diastolic pressure was increased, indicating reduced LV contractility and slowing
      of LV relaxation. These hemodynamic alterations were accompanied by increased
      myocardial formation of 8-iso-prostaglandin F2alpha and oxidized glutathione.
      Vitamin E supplementation improved LV function and significantly attenuated
      myocardial 8-iso-prostaglandin F2alpha and oxidized glutathione accumulation in
      streptozotocin-diabetic rats. CONCLUSIONS: These findings demonstrate the
      usefulness of vitamin E supplementation during the early phases of type I
      diabetes for the prophylaxis of cardiomyopathy and subsequent heart failure.

PMID- 18068625
TI  - Backseat drivers take the wheel.
AB  - Somatic mutations in human cancers are comprised of those that contribute to the
      oncogenic phenotype, driver mutations, and those that reflect the general
      patterns of exposure and disrepair but are otherwise noncontributory, passenger
      mutations. Distinguishing drivers that can be of low frequency in any given tumor
      type from often more numerous passengers is a key challenge. In this issue of
      Cancer Cell, Frohling and colleagues tackle this challenge admirably for the
      known cancer gene FLT3 in acute myeloid leukemia--undertaking a systematic
      resequencing and functional validation approach, identifying important rare
      driver mutations as well as passenger mutations in patients negative for the more
      common activating mutations.

PMID- 18068626
TI  - FGF signaling in prostate tumorigenesis--new insights into epithelial-stromal
      interactions.
AB  - Members of the fibroblast growth factor (FGF) family are believed to play
      critical roles during organogenesis and carcinogenesis via signaling between
      epithelial and stromal compartments. Two new studies in this issue of Cancer Cell
      underscore the importance of FGF signaling in mediating epithelial-stromal
      interactions during prostate carcinogenesis. These papers show that deregulated
      FGF signaling in mouse models of prostate cancer leads to cancer progression and
      promotes an epithelial-mesenchymal transition, suggesting that FGF receptor
      inhibitors may have therapeutic value for prostate cancer treatment.

PMID- 18068627
TI  - New breast cancer genes-discovery at the intersection of complex data sets.
AB  - The identification of genes that contribute to the oncogenic process, including
      those that determine risk of cancer onset, holds the key not only in
      understanding mechanisms of oncogenesis but also in the identification of new
      targets for therapeutic development. Traditional methods of genetics and
      molecular biology have been successful but are slow and laborious. The advent of
      genome technologies, leading to the generation of large data sets describing
      various properties of genes and proteins relevant to cancer phenotypes, has
      afforded a new opportunity for discovery. M. Vidal and colleagues have made use
      of this data, and in particular the integration of various forms of genome-scale
      data, to identify new genes involved in breast cancer.

PMID- 18068628
TI  - Identification of driver and passenger mutations of FLT3 by high-throughput DNA
      sequence analysis and functional assessment of candidate alleles.
AB  - Mutations in the juxtamembrane and kinase domains of FLT3 are common in AML, but
      it is not known whether alterations outside these regions contribute to
      leukemogenesis. We used a high-throughput platform to interrogate the entire FLT3
      coding sequence in AML patients without known FLT3 mutations and experimentally
      tested the consequences of each candidate leukemogenic allele. This approach
      identified gain-of-function mutations that activated downstream signaling and
      conferred sensitivity to FLT3 inhibition and alleles that were not associated
      with kinase activation, including mutations in the catalytic domain. These
      findings support the concept that acquired mutations in cancer may not contribute
      to malignant transformation and underscore the importance of functional studies
      to distinguish "driver" mutations underlying tumorigenesis from biologically
      neutral "passenger" alterations.

PMID- 18068629
TI  - The extracellular matrix protein TGFBI induces microtubule stabilization and
      sensitizes ovarian cancers to paclitaxel.
AB  - The extracellular matrix (ECM) can induce chemotherapy resistance via AKT
      mediated inhibition of apoptosis. Here, we show that loss of the ECM protein
      TGFBI (transforming growth factor beta induced) is sufficient to induce specific
      resistance to paclitaxel and mitotic spindle abnormalities in ovarian cancer
      cells. Paclitaxel-resistant cells treated with recombinant TGFBI protein show
      integrin-dependent restoration of paclitaxel sensitivity via FAK- and Rho
      dependent stabilization of microtubules. Immunohistochemical staining for TGFBI
      in paclitaxel-treated ovarian cancers from a prospective clinical trial showed
      that morphological changes of paclitaxel-induced cytotoxicity were restricted to
      areas of strong expression of TGFBI. These data show that ECM can mediate taxane
      sensitivity by modulating microtubule stability.

PMID- 18068630
TI  - Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo.
AB  - A key characteristic of stem cells and cancer cells is their ability to self
      renew. To test if Wnt signaling can regulate the self-renewal of both stem cells
      and cancer cells in the hematopoietic system, we developed mice that lack beta
      catenin in their hematopoietic cells. Here we show that beta-catenin-deficient
      mice can form HSCs, but that these cells are deficient in long-term growth and
      maintenance. Moreover, beta-catenin deletion causes a profound reduction in the
      ability of mice to develop BCR-ABL-induced chronic myelogenous leukemia (CML),
      while allowing progression of acute lymphocytic leukemia (ALL). These studies
      demonstrate that Wnt signaling is required for the self-renewal of normal and
      neoplastic stem cells in the hematopoietic system.

PMID- 18068631
TI  - ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary
      progenitors via activation of AP1 complex.
AB  - To better understand the cellular origin of breast cancer, we developed a mouse
      model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein,
      the product of the t(12;15)(p13;q25) translocation characteristic of human
      secretory breast carcinoma. Activation of EN expression in mammary tissues by Wap
      Cre leads to fully penetrant, multifocal malignant breast cancer with short
      latency. We provide genetic evidence that, in nulliparous Wap-Cre;EN females,
      committed alveolar bipotent or CD61(+) luminal progenitors are targets of
      tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors
      through activation of the AP1 complex. Given the increasing relevance of
      chromosomal translocations in epithelial cancers, such mice serve as a paradigm
      for the study of their genetic pathogenesis and cellular origins, and generation
      of preclinical models.

PMID- 18068632
TI  - Inducible FGFR-1 activation leads to irreversible prostate adenocarcinoma and an
      epithelial-to-mesenchymal transition.
AB  - Fibroblast Growth Factor Receptor-1 (FGFR1) is commonly overexpressed in advanced
      prostate cancer (PCa). To investigate causality, we utilized an inducible FGFR1
      (iFGFR1) prostate mouse model. Activation of iFGFR1 with chemical inducers of
      dimerization (CID) led to highly synchronous, step-wise progression to
      adenocarcinoma that is linked to an epithelial-to-mesenchymal transition (EMT).
      iFGFR1 inactivation by CID withdrawal led to full reversion of prostatic
      intraepithelial neoplasia, whereas PCa lesions became iFGFR1-independent. Gene
      expression profiling at distinct stages of tumor progression revealed an increase
      in EMT-associated Sox9 and changes in the Wnt signaling pathway, including Fzd4,
      which was validated in human PCa. The iFGFR1 model clearly implicates FGFR1 in
      PCa progression and demonstrates how CID-inducible models can help evaluate
      candidate molecules in tumor progression and maintenance.

PMID- 18068634
TI  - Proarrhythmic effect of altered ventricular activation sequence in patients with
      permanent pacemaker.

PMID- 18068633
TI  - Enhanced paracrine FGF10 expression promotes formation of multifocal prostate
      adenocarcinoma and an increase in epithelial androgen receptor.
AB  - Enhanced mesenchymal expression of FGF10 led to the formation of multifocal PIN
      or prostate cancer. Inhibition of epithelial FGFR1 signaling using DN FGFR1 led
      to reversal of the cancer phenotype. A subset of the FGF10-induced carcinoma was
      serially transplantable. Paracrine FGF10 led to an increase in epithelial
      androgen receptor and synergized with cell-autonomous activated AKT. Our
      observations indicate that stromal FGF10 expression may facilitate the multifocal
      histology observed in prostate adenocarcinoma and suggest the FGF10/FGFR1 axis as
      a potential therapeutic target in treating hormone-sensitive or refractory
      prostate cancer. We also show that transient exposure to a paracrine growth
      factor may be sufficient for the initiation of oncogenic transformation.

PMID- 18068635
TI  - Pulmonary vein reentry--properties and size matter: insights from a computational
      analysis.
AB  - BACKGROUND: Pulmonary vein (PV) ablation plays an important role in atrial
      fibrillation (AF) therapy but suffers from a limited mechanistic understanding of
      PV arrhythmogenicity. Rapid focal activation has been suggested, but some
      evidence points to underlying reentry. OBJECTIVE: This study was performed to
      evaluate how the electrophysiological properties of PVs may make them a site for
      reentry and to analyze specifically the roles of PV dimensions and coupling
      properties. METHODS: A computer model designed to efficiently reproduce
      electrophysiological behaviors was fit to action potentials from canine left
      atria (LA) and PVs. To assess structural and functional arrhythmogenic
      determinants, an idealized PV of varying length and circumference was attached to
      LA tissue, and 5 seconds of activity after extrastimulation were simulated.
      RESULTS: PV reentrant activity depended critically on vein size and coupling
      properties. With cumulative removal of transverse and longitudinal connections,
      sustained (n=23) or nonsustained (n=93) reentries could be observed (687
      simulations) for veins 1-3 cm long and 1-2 cm in circumference. The prevalence of
      sustained reentry increased with PV length (8% for 1 cm vs. 22% and 31% for 2 and
      3 cm, respectively; P<.05 for each). The PV circumference did not affect the
      incidence of sustained reentry (25%, 17%, and 21% for 1-, 1.5-, and 2-cm
      circumferences; P=NS), but the number of reentrant events increased from 12/201
      simulations for PVs with a 1-cm circumference to 48/232 and 56/254 events for PVs
      with 1.5- and 2-cm circumferences, respectively (P<.05). Sustained reentry cycle
      lengths were approximately 200-250 ms (16/23), except for the longest PVs.
      CONCLUSION: Reentry occurs readily in PVs with realistic properties in the
      context of specific connection heterogeneities. Reentry properties and incidence
      depend on PV anisotropy and dimensions but could certainly contribute
      significantly to PV arrhythmogenesis.

PMID- 18068636
TI  - Pulmonary veins and the initiation of atrial fibrillation: are we getting closer
      to understanding their role?

PMID- 18068637
TI  - Atrial fibrillation in the elderly: mechanisms and management.

PMID- 18068638
TI  - Short runs of irregular narrow QRS tachycardia: what is the mechanism?

PMID- 18068639
TI  - Computed tomography image-guided catheter ablation of a focal atrial tachycardia
      from the noncoronary sinus of Valsalva.

PMID- 18068640
TI  - Clinical considerations for allied professionals: radiation safety and protection
      in the electrophysiology lab.

PMID- 18068642
TI  - Coexistence in competition models with density-dependent mortality.
AB  - We consider a two-competitor/one-prey model in which both competitors exhibit a
      general functional response and one of the competitors exhibits a density
      dependent mortality rate. It is shown that the two competitors can coexist upon
      the single prey. As an example, we consider a two-competitor/one-prey model with
      a Holling II functional response. Our results demonstrate that density-dependent
      mortality in one of the competitors can prevent competitive exclusion. Moreover,
      by constructing a Liapunov function, the system has a globally stable positive
      equilibrium.

PMID- 18068643
TI  - Girolline interferes with cell-cycle progression, but not with translation.
AB  - Girolline is a 2-aminoimidazole derivative with cytotoxic activity. It affects
      the survival of exponentially growing leukaemic cultured cells and has a
      significant antitumour activity on grafted murine tumours in vivo. In vitro
      studies showed that girolline affected protein synthesis by interfering with the
      translation termination process. Here, we investigate the effect of girolline on
      translation termination in human cultured cells. We show that girolline neither
      induces an increase in translational readthrough of stop codons nor affects the
      polysome profile in treated cells. This suggests that girolline does not act on
      translation in vivo. Then, we examine the effect of girolline on cell-cycle
      progression and we show that girolline induces an arrest of the cell cycle at the
      G2 stage.

PMID- 18068644
TI  - Effects of ionizing radiation on the activity of the major hepatic enzymes
      implicated in bile acid biosynthesis in the rat.
AB  - In the days following high-dose radiation exposure, damage to small intestinal
      mucosa is aggravated by changes in the bile acid pool reaching the gut.
      Intestinal bile acid malabsorption, as described classically, may be associated
      with altered hepatic bile acid biosynthesis, which was the objective of this
      work. The activity of the main rate-limiting enzymes implicated in the bile acid
      biosynthesis were evaluated in the days following an 8-Gy gamma(60)Co total body
      irradiation of rats, with concomitant determination of biliary bile acid profiles
      and intestinal bile acid content. Modifications of biliary bile acid profiles,
      observed as early as the first post-irradiation day, were most marked at the
      third and fourth day, and resulted in an increased hydrophobicity index. In
      parallel, the intestinal bile acids' content was enhanced and hepatic enzymatic
      activities leading to bile acids were changed. A marked increase of sterol 12
      alpha-hydroxylase and decrease of oxysterol 7 alpha-hydroxylase activity was
      observed at day 3, whereas both cholesterol 7 alpha-hydroxylase and oxysterol 7
      alpha-hydroxylase activities were decreased at day 4 after irradiation. These
      results show, for the first time, radiation-induced modifications of hepatic
      enzymatic activities implicated in bile acid biosynthesis and suggest that they
      are mainly a consequence of radiation-altered intestinal absorption, which
      induces a physiological response of the enterohepatic bile acid recirculation.

PMID- 18068645
TI  - [Intra-individual heterostyly in Atriplex halimus L. (Amaranthaceae)].
AB  - Classically, the Atriplex halimus L. female flower is perianthless, has two
      bracteoles, one ovary and one style. Considering bracteoles, one can distinguish,
      among the representatives of two Tunisian populations, three phenotypes of female
      flowers, each of them being distributed in three types according to the style
      length. Male flowers produce three types of pollen. This is the only known
      example of intra-individual heterostyly in unisexual flowers. These results
      question the classical concept of individual. The authors discuss a possible
      process implying indirectly hybridisation and introgression between A. halimus
      and A. nummularia.

PMID- 18068646
TI  - Effects of salicylhydroxamic acid on the proliferation of Atriplex and murine
      neuroblastoma cells, and on Drosophila egg laying and development.
AB  - Salicylhydroxamic acid (SHAM) inhibits the proliferation of cultured plant
      (Atriplex halimus) and murine neuroblastoma cells with IC50 of 90 and 250 microM,
      respectively. After 2 h of application, SHAM induces an acceleration of the
      neuroblastoma cell cycle from G1/S to G2 phases and, after 6 h, it induces an
      accumulation of the cells in S phase and a cell swelling. Up to 300 microM, SHAM
      is not cytotoxic and does not induce electrophysiological differentiation of
      neuroblastoma cells. When Drosophila females are grown in media containing 0.6
      1.25 mM SHAM, the rate and number of laid eggs are increased. Furthermore, SHAM
      stimulates the different development stages from embryo to adult. A general
      interpretation of the effects of SHAM on cell proliferation and differentiation
      is proposed.

PMID- 18068647
TI  - [Effects of Buthus occitanus tunetanus envenomation on an experimental murine
      model of gestation].
AB  - Scorpion envenoming is less studied in pregnant victims. In this work, the effect
      of Buthus occitanus tunetanus on parturition in late pregnancy was studied in an
      animal model. Four groups of six primigravid female rats, each one at the 22nd
      day of pregnancy, were used. The first two groups had received an intra
      peritoneal injection of 500 microg/kg of Buthus occitanus tunetanus crude venom
      or a physiological saline solution and left until foetal delivery. Then, the time
      elapsed until the first pup delivery and that separating the first and latest
      ones were measured. The other two groups served for the uterine
      electrophysiological activity exploration. Rats were anaesthetized, artificially
      ventilated and had received an intraperitoneal injection of 500 microg/kg of
      Buthus occitanus tunetanus crude venom or a physiological saline solution. Our
      results showed a significant increase of the latency to foetal delivery, labour
      time, and uterine contractile activity in envenomed rats compared to controls.
      Such signs are usually seen in dynamic dystocia. It was concluded that Buthus
      occitanus tunetanus envenoming might induce a dynamic dystocia, when it occurred
      in late pregnancy.

PMID- 18068648
TI  - Effect of subchronic exposure to tetradifon on bone remodelling and metabolism in
      female rat.
AB  - This study investigates the effect of subchronic exposure to tetradifon, an
      organochlorine pesticide with an oestrogen-like structure, in female rat. A
      single cumulative dose of 2430 mg/kg BW was administrated orally for 12 female
      rats of 190 g BW. Twelve non-treated additional rats have served as controls.
      Animals were sacrificed after 6 and 12 weeks of treatment. We studied bone
      remodelling through histomorphometry and scanning electron microscopy (SEM)
      analyses. The serum and the right femora were used to determine phosphatase
      alkaline (AlkP) and/or calcium and phosphorus content. No sign of toxicity was
      observed until the end of the experiment. The SEM results revealed no structural
      alteration of the treated animal bone tissue. However, in both treated groups, we
      have noted an increase in the trabecular distance and a heterogeneous aspect of
      the endosteum that could be explained by bone-remodelling disturbance, with
      relative delay of ossification. Following histomorphomotric analysis, these
      results were coupled with significant increases in Tb.Th and OS/BS. Elsewhere,
      tetradifon intoxication increased significant serum AlkP level in the group
      treated for 12 weeks, which could be explained by an osteoblastic hyperactivity.
      Tetradifon intoxication decreased significantly bone calcium end phosphorus
      contents. Tetradifon seems not to exert major effects on bone remodelling.
      However, the osteoblastic hyperactivity could be explained by the oestrogen-like
      activity of tetradifon and its fatty metabolism. In fact, oestrogen inhibits bone
      remodelling, and enhances bone formation, which could result in an increase of
      the osteoid surface and explain the relative delay of ossification.

PMID- 18068649
TI  - Alterations in lipid peroxidation, electrolyte leakage, and proline metabolism in
      Catharanthus roseus under treatment with triadimefon, a systemic fungicide.
AB  - Triadimefon (TDM), a systemic fungicide with non-traditional plant-growth
      regulator properties, was administered to Catharanthus roseus (L.) G. Don. plants
      in order to determine its effects on oxidative injury in terms of H2O2 content,
      lipid peroxidation (LPO), electrolyte leakage (EL), protein and amino acid
      contents, as well as proline metabolism. The LPO, estimated as thiobarbituric
      acid-reactive substances (TBARS), decreased under TDM treatment. It was found
      that H2O2 and EL were reduced under TDM treatment when compared to control. TDM
      treatment caused a significant increase in the protein and amino acid contents.
      Glycine betaine (GB) and proline (PRO) significantly accumulated in C. roseus
      under stress arisen from fungicide applications. Proline oxidase (PROX)
      activities reduce the PRO content and gamma-glutamyl kinase (gamma-GK)
      accelerates the synthesis of PRO. Under TDM treatment, the activity of PROX
      decreased and the gamma-GK activity increased. From our results, it is suggested
      that fungicide triadimefon causes activation of metabolic processes in the
      medicinal plant Catharanthus roseus. These findings are of great significance for
      the cultivation of this medicinal plant, as it was previously reported that TDM
      causes an enhancement of antioxidant metabolism and ajmalicine production in C.
      roseus.

PMID- 18068650
TI  - Ant species diversity in the 'Grands Causses' (Aveyron, France): In search of
      sampling methods adapted to temperate climates.
AB  - This study aimed at showing the applicability of using a combination of four
      sampling methods (i.e., Winkler extractors, pitfall traps, baiting and manual
      collection), something most often conducted in the tropics, to create an
      inventory of ant species diversity in temperate environments. We recorded a total
      of 33 ant species in the Grands Causses by comparing three vegetal formations: a
      steppic lawn ('causse' sensu stricto), which was the most species-rich (29
      species), followed by an oak grove (22 species) and a pine forest (17 species).
      No sampling method alone is efficient enough to provide an adequate sampling, but
      their combination permits one to make a suitable inventory of the myrmecofauna
      and to obtain information on the ecology of these ant species.

PMID- 18068651
TI  - [Comparison of coleopteran and spider communities between a reforested area and a
      still steppe area in a pre-Saharan region of Algeria].
AB  - In the pre-Saharan region of Djelfa (Algeria), the coleopteran and spider
      communities are compared between two neighbouring ecosystems, the one kept as a
      steppe, the other one reforested with Aleppo pine. In three plots in each area,
      pitfall (Barber) traps were sampled monthly during one year and arthropods were
      identified and counted. Two thousand five hundred and fifty-seven individuals,
      distributed into 95 species, were collected, belonging to four coleopteran
      families (Carabidae, Scarabaeidae, Tenebrionidae, and Curculionidae), and 14
      spider families. The Tenebrionidae (43% of the species and 87% of the
      individuals) were clearly the most represented group of insects, numerically
      because of the considerable abundance of Pimelia mauritanica in the reforested
      area, where this species accounted for half the total number of catches. Among
      the spiders, the Gnaphosidae represented 40% of the individuals and one-third of
      the species. The total species richness of the two areas was the same, but,
      considering the total number of collected species, individual abundance and
      diversity indexes (Shannon, Simpson) were lower in the reforested zone. However,
      these parameters became fully comparable when excluding P. mauritanica from the
      calculations. Without P. mauritanica, numbers and species richness of
      Tenebrionidae were similar in both areas. Curculionidae had higher populations
      and higher species diversity in the steppe area, while Scarabeidae were equally
      abundant in the two ecosystems types. The number, the species richness, and the
      diversity indexes of Carabidae were much lower in the reforested area than in the
      steppe one. The opposite was observed with spiders. Nevertheless, more or less
      important variations in the number of individuals, in one or another direction
      depending on the species, existed among each taxonomic group. It is concluded
      that reforestation has not changed biological diversity, but has induced dramatic
      modifications in the organisation and functioning of the arthropod communities.

PMID- 18068652
TI  - So what is a keloid scar?

PMID- 18068653
TI  - Telemedicine for acute plastic surgical trauma and burns.
AB  - Visual images can enhance communication over a distance. In the UK, plastic
      surgery provides services over large distances by a 'hub and spoke' model.
      Telemedicine could help to increase the efficiency of service for plastic surgery
      patients. Telemedicine, along with the impending Electronic Patient Record system
      could combine to improve communication, patient triage, record keeping, audit and
      could lead to a better quality of clinical care. Another benefit could be
      significant cost savings. We report our experience of the introduction of
      telemedicine to a Regional Plastic Surgery Service. Our first study compared
      assessments from images and patient examinations, which gave us confidence in the
      use of images [Jones SM, Milroy C, Pickford MA. Telemedicine in acute plastic
      surgical trauma and burns. Ann R Coll Surg Engl 2004;86:239-42]. We proceeded to
      a 10-week evaluation of all 973 referrals to our unit. We found that the system
      was used for a wide variety of injuries and for 42% of the 452 patients where the
      system was available. Initial resistance was overcome by the ease of use of the
      system, with both receiving and referring clinicians reporting benefits. The
      third phase was a 12-week prospective cohort study of 996 patients comparing the
      referrals with and without the telemedicine system. The system was available for
      389 patients, and used for 243 patients (63%). The groups were analysed by a chi
      squared test and confidence interval calculation. We demonstrated a significant
      difference in the initial management of patients, with 10% more being booked
      directly to our Day Surgery Unit. There was a decrease in number of occasions
      when we were unable to accept a patient due to a lack of capacity. We found no
      change in the patients being managed with telephone only advice. We found that
      telemedicine is a valuable method of providing useful preliminary information in
      the referral process for injured patients and often significantly modifies their
      treatment and/or management plan. This has implications for the use of
      Information Technology resources and potentially the delivery of healthcare in
      relation to the management of injured patients.

PMID- 18068654
TI  - Marjolin's ulcer revisited--basal cell carcinoma arising from grenade fragments?
      Case report and review of the literature.
AB  - BACKGROUND: Marjolin's ulcer is a rare and often aggressive cutaneous malignancy
      arising in previously traumatized or chronically inflamed skin. METHOD:  CASE
      REPORT: A 79-year-old World War II veteran developed basal cell carcinoma (BCC)
      at the site of a war wound. The tumour developed in relation to several metal
      grenade fragments. With a disease-free interval of 61 years between injury and
      onset of complications the patient had one of the longest latency periods of
      tumour development described so far. RESULTS: Review of the literature reveals
      only five cases of relation between grenade fragments and malignancy formation.
      Presence of foreign bodies has been described as possible aetiology for
      malignancy development. Explosives and additives contain several mutagenic and
      tumourigenic substances. We hypothesize a causal connection between the grenade
      fragments and the development of BCC. Considering the long period of latency
      between injury and tumour development we suggest grenade injury with left
      fragments in soft tissue to be a new origin of Marjolin's ulcer.

PMID- 18068655
TI  - Heparin-induced thrombocytopenia syndrome as a cause of flap failure: a report of
      two cases.
AB  - BACKGROUND: Flap failure is a major complication in reconstructive plastic
      surgery. One of the most frequent etiologies of flap failure is venous
      thrombosis. However, infrequent causes also need to be explored, especially when
      faced with recurrent thrombosis. Heparin is frequently used in the prevention of
      venous thrombosis; however, the use of the medication itself may cause a serious
      thromboembolic state via an immune-related pathophysiological process. This
      adverse reaction to heparin may be life threatening. CASE PRESENTATION: We
      present two cases, one pedicled and one free flap, with venous congestion
      concomitant to heparin-induced thrombocytopenia syndrome, in conjunction with
      severe life-threatening sequelae. CONCLUSIONS: Heparin-induced thrombocytopenia
      syndrome can be the cause of postoperative venous congestion. It is necessary to
      be alert for this syndrome in the presence of recurrent unexplained venous
      thrombosis or thrombocytopenia in patients receiving anticoagulation therapy.

PMID- 18068656
TI  - Atypical arteriole anastomoses for fingertip replantations under digital block.
AB  - Reconstructive microsurgery is now in a new stage of supermicrosurgery. With this
      technique, very tiny (0.3mm) vascular anastomoses are possible. In this paper, we
      describe two cases of successful fingertip replantations employing arteriole
      (terminal branch of digital artery) anastomoses, the arteriole graft being
      obtained from the same fingertip defect, reverse arteriole flow to subdermal
      venule, and delayed venular drainage for venous congestion. These atypical tiny
      vascular anastomoses were successfully carried out under digital block.

PMID- 18068657
TI  - Bisphosphonates and avascular necrosis of the mandible: case report and review of
      the literature.
AB  - BACKGROUND: Avascular necrosis of the mandible or maxilla is being recognized
      with increasing frequency in patients who are being treated with bisphosphonates
      for metastatic cancers. METHODS AND RESULTS: A patient who was treated for
      avascular necrosis following treatment with bisphosphonates for multiple myeloma
      is presented. CONCLUSION: Prophylactic and preventative measures should be
      instituted prior to commencing treatment with bisphosphonates to minimize the
      risk of developing avascular necrosis.

PMID- 18068658
TI  - Jaw avascular osteonecrosis after treatment of multiple myeloma with zoledronate.
AB  - PURPOSE: Multiple myeloma, the second most common haematopoietic cancer, which
      represents the collection of plasma-cell neoplasms that invariably becomes fatal
      when self-renewing myeloma cells begin unrestrained proliferation. The major
      clinical manifestation of multiple myeloma is related to the loss of bone through
      osteolysis. This can lead to pathologic fractures, spinal cord compression,
      hypercalcaemia, and pain. It is also a major cause of morbidity and mortality in
      these patients, who frequently require radiation therapy, surgery and analgesic
      medications. Bisphosphonates are specific inhibitors of osteoclastic activity,
      and are currently used to prevent bone complications and to treat malignant
      hypercalcaemia in patients with multiple myeloma, or bone metastases from breast
      and prostate cancers. Hence, osteonecrosis of the mandible has been reported in
      three patients from Centro Hospitalar de Vila Nova de Gaia (CHVNG) with multiple
      myeloma treated for over 18-48 months with intravenous zoledronate, commonly
      prescribed for multiple myeloma therapy. Although, this report alerts clinicians
      about the potential complication of bone necrosis in patients receiving
      bisphosphonate therapy, many questions remain concerning the underlying
      pathogenesis of this process. PATIENTS AND METHODS: The medical and dental
      records of three patients with multiple myeloma, who were treated in CHVNG in the
      past 4 years, were reviewed. These three patients presented exposed bone and
      osteonecrosis of the mandible, and shared one common clinical feature: all of
      them were treated with bisphosphonate zoledronate, administered intravenously for
      long periods. Sequential orthopantomograms (OPGs) and histological evaluation
      have been analysed from the biopsies of the non healing dental extraction sites
      of these patients. RESULTS: After a routine dental extraction, these patients
      developed avascular osteonecrosis of the mandible and secondary bone infection
      with Actinomyces israelii (actinomycotic osteomyelitis), with no evidence of
      metastatic disease evaluated by biopsy. In these three described clinical cases,
      surgical debridment without flap elevation, intensive antibiotherapy and the
      suspension of the zoledronate treatment allowed a partial recovery of the
      patients. The purpose of this clinical report is to point out that patients
      suffering from multiple myeloma can develop bone osteonecrosis induced by
      treatment with bisphosphonates. Research to determine the mechanism of this
      dental phenomenon is needed to fully validate and substantiate the possible link
      between bisphosphonate treatment of multiple myeloma or other cancer diseases and
      avascular osteonecrosis of the jaws. Until then, clinicians involved in the care
      of patients at risk should consider this possible complication.

PMID- 18068659
TI  - Dumbbell-formed lipomas under the zygomatic arch.
AB  - Two cases of dumbbell-shaped lipoma under the zygomatic arch and the therapeutic
      courses are described. Both tumours were present in the buccal and temporal
      processes and the isthmus, which showed dumbbell forms occupying temporal and
      infratemporal fossae on coronal MR images. According to the location, the tumours
      seemed to be derived from a masticatory fat pad. The tumours were completely
      excised via a temporal and small cheek skin incision, with no postoperative
      complications. Over the 5-year follow-up period, both cases have shown good
      function and aesthetics, and no recurrences have been observed.

PMID- 18068660
TI  - Precursor ion discovery on a hybrid quadrupole-time-of-flight mass spectrometer
      for gonadotropin-releasing hormone detection in complex biological mixtures.
AB  - The gonadotropin-releasing hormone (GnRH) family includes several
      hypophysiotropic peptides occupying a central position in the regulatory loop
      controlling reproduction. Studies are still under way to clarify its biological
      role and evolutionary implication. Although sequencing of multiple genomes is
      bringing further advances in the understanding of the evolution of GnRH, there is
      still a need for biochemical studies aiming to identify GnRH from different
      species. Using a hybrid quadrupole-time-of-flight (Q-TOF) instrument, a new
      method for selective and sensitive GnRH detection and characterization from
      tissue extracts has been developed. The method uses the "precursor ion discovery"
      mode based on the capability of the Q-TOF analyzer to quickly record alternate
      mass spectra at low and high collision energy of precursor and product ion
      spectra, respectively, following liquid chromatographic separation of complex
      biological mixtures. The method exploits the selective detection of a specific
      b(2) product ion at m/z 249.1, corresponding to the N-terminus dipeptide
      pyroglutamic acid-histidine, highly conserved among nearly all species (22 of
      24), and deriving from the preferential fragmentation of GnRHs carrying the
      dipeptide. Importantly, the method also includes acquisition of the product ion
      spectra from any candidate precursor ion, thereby allowing the determination of
      sequence information to confirm the GnRH identity or to isolate new ones.

PMID- 18068661
TI  - Energetics of the interactions of human serum albumin with cationic surfactant.
AB  - The heat capacity changes for interaction of human serum albumin (HSA) and a
      cationic surfactant-cetylpyridinium chloride (CPC), were studied at conditions
      close to physiological (50mM HEPES or phosphate buffer, pH 7.4 and 160mM NaCl)
      carrying out isothermal calorimetric titrations (ITC) at various temperatures (20
      40 degrees C). ITC measurements indicated that the small endothermic changes
      associated with CPC demicellization were temperature independent at these
      conditions. Surprisingly, important enthalpy changes associated with binding of
      CPC to HSA were exothermic and temperature independent at lower concentrations
      (below 0.022mM) of CPC and endothermic and temperature dependent at higher
      concentrations of CPC. The values of heat capacity changes were obtained for each
      studied concentration of CPC from the plot of enthalpy changes vs temperature.
      The obtained results demonstrate the temperature independence of heat capacity
      changes at entire range of studied CPC concentrations. Both enthalpograms and
      heat capacity curves indicate the two-step mechanism of HSA folding changes due
      to its interactions with CPC. The first step corresponds to transition from
      native state to partially unfolded state and the second to unfolding and to the
      loss of tertiary structure. The analysis of the results indicates that
      predominant cooperative unfolding occurs at CPC/HSA molar ratio region between 25
      and 30. Such information could not be extracted from thermograms and describes
      the role of heat capacity as a major thermodynamic quantity giving insight on
      physical, mechanistic and even atomic-level into how HSA may unfold and interact
      with CPC. The effect of CPC binding on HSA intrinsic fluorescence, UV-Vis and CD
      spectra were also examined. Hence, the analysis of spectral data confirms the ITC
      results about the biphasic mechanism of HSA folding changes induced by CPC. The
      CD measurement also represents the conservation of considerable secondary
      structure of HSA due to interaction with CPC.

PMID- 18068663
TI  - Characterization of a novel congenic strain of diabetic fatty (WBN/Kob-Lepr(fa))
      rat.
AB  - The WBN/Kob-Lepr(fa) rat is a new congenic strain for the fa allele of the leptin
      receptor gene (Lepr). Homozygous (fa/fa) WBN/Kob-Lepr(fa) rats provide a model of
      non-insulin-dependent diabetes with obesity. Here, we describe the
      characteristics of this new animal model in detail. At 7 weeks of age, both male
      and female obese WBN/Kob rats showed inflammatory cell infiltration of the
      pancreas that suggested pan-pancreatitis and an abnormal OGTT. At 3 months of
      age, both male and female obese WBN/Kob rats developed overt diabetes mellitus
      associated with severe chronic pancreatitis. In contrast, lean female WBN/Kob
      rats do not develop pancreatitis or diabetes. In WBN/Kob rats, this mutation
      might promote the onset of severe pancreatitis, leading to the rapid development
      of diabetes mellitus.

PMID- 18068664
TI  - The construction and in vitro testing of photo-activatable cancer targeting
      folated anti-CD3 conjugates.
AB  - The construction and in vitro testing of a photo-activatable anti-tumour immuno
      regulatory antibody is described. In this 'cloaked' folated anti-CD3 antibody
      conjugate, the folate portion of the conjugate is free to bind to folate receptor
      expressing cancer cells, whilst the anti-CD3 activity is effectively rendered
      inert by a coating of photo-labile 2-nitrobenzyl groups. On irradiation with UV-A
      light the activity of the anti-CD3 antibody is restored, not only when it is
      required, but more importantly, only where it is required. The conjugate can then
      attract killer T-cells to the surface of the tumour cells and kill them.
      Unirradiated normal tissues, to which the conjugate has been targeted by specific
      and non-specific binding, remain unharmed. We believe that these 'photo
      switchable' conjugates could be used to markedly improve the targeting of the
      immune response to folate receptor (FR) expressing ovarian and breast cancers
      whilst minimising the side effects in the rest of the body.

PMID- 18068665
TI  - Thermodynamic evidence of non-muscle myosin II-lipid-membrane interaction.
AB  - A unique feature of protein networks in living cells is that they can generate
      their own force. Proteins such as non-muscle myosin II are an integral part of
      the cytoskeleton and have the capacity to convert the energy of ATP hydrolysis
      into directional movement. Non-muscle myosin II can move actin filaments against
      each other, and depending on the orientation of the filaments and the way in
      which they are linked together, it can produce contraction, bending, extension,
      and stiffening. Our measurements with differential scanning calorimetry showed
      that non-muscle myosin II inserts into negatively charged phospholipid membranes.
      Using lipid vesicles made of DMPG/DMPC at a molar ratio of 1:1 at 10mg/ml in the
      presence of different non-muscle myosin II concentrations showed a variation of
      the main phase transition of the lipid vesicle at around 23 degrees C. With
      increasing concentrations of non-muscle myosin II the thermotropic properties of
      the lipid vesicle changed, which is indicative of protein-lipid
      interaction/insertion. We hypothesize that myosin tail binds to acidic
      phospholipids through an electrostatic interaction using the basic side groups of
      positive residues; the flexible, amphipathic helix then may partially penetrate
      into the bilayer to form an anchor. Using the stopped-flow method, we determined
      the binding affinity of non-muscle myosin II when anchored to lipid vesicles with
      actin, which was similar to a pure actin-non-muscle myosin II system. Insertion
      of myosin tail into the hydrophobic region of lipid membranes, a model known as
      the lever arm mechanism, might explain how its interaction with actin generates
      cellular movement.

PMID- 18068666
TI  - Ghrelin raises [Ca2+]i via AMPK in hypothalamic arcuate nucleus NPY neurons.
AB  - Ghrelin, an orexigenic hormone, directly activates neuropeptide (NPY) neurons in
      the hypothalamic arcuate nucleus (ARC), and thereby stimulates food intake. The
      hypothalamic level of AMP-activated protein kinase (AMPK), an intracellular
      energy sensor, is activated by peripheral and central administration of ghrelin.
      We examined whether ghrelin regulates AMPK activity in NPY neurons of the ARC.
      Single neurons were isolated from the ARC and cytosolic Ca(2+) concentration
      ([Ca(2+)](i)) was measured by fura-2 microfluorometry, followed by
      immunocytochemical identification of NPY, phospho-AMPK, and phospho-acetyl-CoA
      carboxylase (ACC). Ghrelin and AICAR, an AMPK activator, increased [Ca(2+)](i) in
      neurons isolated from the ARC. The ghrelin-responsive neurons highly overlapped
      with AICAR-responsive neurons. The neurons that responded to both ghrelin and
      AICAR were primarily NPY-immunoreactive neurons. Treatment with ghrelin increased
      phosphorylation of AMPK and ACC. An AMPK inhibitor, compound C, suppressed
      ghrelin-induced [Ca(2+)](i) increases. These results demonstrate that ghrelin
      increases [Ca(2+)](i) via AMPK-mediated signaling in the ARC NPY neurons.

PMID- 18068662
TI  - Biology and regulation of ectoplasmic specialization, an atypical adherens
      junction type, in the testis.
AB  - Anchoring junctions are cell adhesion apparatus present in all epithelia and
      endothelia. They are found at the cell-cell interface (adherens junction (AJ) and
      desmosome) and cell-matrix interface (focal contact and hemidesmosome). In this
      review, we focus our discussion on AJ in particular the dynamic changes and
      regulation of this junction type in normal epithelia using testis as a model.
      There are extensive restructuring of AJ (e.g., ectoplasmic specialization, ES, a
      testis-specific AJ) at the Sertoli-Sertoli cell interface (basal ES) and Sertoli
      elongating spermatid interface (apical ES) during the seminiferous epithelial
      cycle of spermatogenesis to facilitate the migration of developing germ cells
      across the seminiferous epithelium. Furthermore, recent findings have shown that
      ES also confers cell orientation and polarity in the seminiferous epithelium,
      illustrating that some of the functions initially ascribed to tight junctions
      (TJ), such as conferring cell polarity, are also part of the inherent properties
      of the AJ (e.g., apical ES) in the testis. The biology and regulation based on
      recent studies in the testis are of interest to cell biologists in the field, in
      particular their regulation, which perhaps is applicable to tumorigenesis.

PMID- 18068667
TI  - Is Kir6.1 a subunit of mitoK(ATP)?
AB  - The subunit composition of the mitochondrial ATP-sensitive K(+)-channel
      (mitoK(ATP)) is unknown, though some suspect a role for the inward rectifier,
      Kir6.1, based largely on antibody studies of heart mitochondria. To ascertain the
      molecular identity of mitoK(ATP) we therefore sought to purify this putative
      mitochondrial Kir6.1, and conclusively identify the subunits by mass
      spectrometry. Immunoblots, conducted with two commercially available antibodies,
      revealed two distinct signals in isolated heart mitochondria, of 51 and 48kDa,
      respectively. Localization was confirmed by either immuno-gold electron
      microscopy or by immunofluorescence. Each putative Kir6.1 species was extracted,
      purified, and identified by LC-MS/MS. The 51kDa band was identified as NADH
      dehydrogenase flavoprotein 1, while the preponderant protein in the 48-kDa band
      was mitochondrial isocitrate dehydrogenase (NADP form). 1D-, 2D-, and native gel
      analyses were consistent with these assignments. The data suggest it is premature
      to assign Kir6.1 a role in mitoK(ATP) on the basis of immunoreactivity alone.

PMID- 18068668
TI  - Development of amphiphilic gamma-PGA-nanoparticle based tumor vaccine: potential
      of the nanoparticulate cytosolic protein delivery carrier.
AB  - Nanoscopic therapeutic systems that incorporate biomacromolecules, such as
      protein and peptides, are emerging as the next generation of nanomedicine aimed
      at improving the therapeutic efficacy of biomacromolecular drugs. In this study,
      we report that poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are
      excellent protein delivery carriers for tumor vaccines that delivered antigenic
      proteins to antigen-presenting cells and elicited potent immune responses.
      Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins
      through cytosolic translocation from the endosomes, which is a key process of
      gamma-PGA NP-mediated anti-tumor immune responses. Our findings suggest that the
      gamma-PGA NP system is suitable for the intracellular delivery of protein-based
      drugs as well as tumor vaccines.

PMID- 18068669
TI  - The Ca2+ ATPase of cardiac sarcoplasmic reticulum: Physiological role and
      relevance to diseases.
AB  - The Ca(2+) ATPase of sarcoplasmic reticulum has a prominent role in
      excitation/contraction coupling of cardiac muscle, as it induces relaxation by
      sequestering Ca(2+) from the cytoplasm. The stored Ca(2+) is in turn released to
      trigger contraction. We review here experiments demonstrating that in cardiac
      myocytes Ca(2+) signaling and contractile activation are strongly altered by
      pharmacological inhibition or transcriptional down-regulation of SERCA. On the
      other hand, kinetics, and intensity of Ca(2+) signaling are improved by SERCA
      overexpression following delivery of exogenous cDNA by adenovirus vectors.
      Experiments on adrenergic hypertrophy demonstrate SERCA down-regulation,
      consistent with its pathogenetic involvement in cardiac hypertrophy and failure,
      as also shown in other experimental models and clinical studies. Compensation by
      alternate Ca(2+) signaling proteins, including functional activation and
      increased expression of Na(+)/Ca(2+) exchanger and TRPC proteins has been
      observed. These compensatory mechanisms, including calcineurin activation, remain
      to be clarified and are a most important subject of current studies.

PMID- 18068670
TI  - Biotransformation of (+)-catechin into taxifolin by a two-step oxidation: primary
      stage of (+)-catechin metabolism by a novel (+)-catechin-degrading bacteria,
      Burkholderia sp. KTC-1, isolated from tropical peat.
AB  - Peat contains various persistent compounds derived from plant materials. We
      isolated a novel (+)-catechin-degrading bacterium, Burkholderia sp. KTC-1 (KTC
      1), as an example of a bacterium capable of degrading persistent aromatic
      compounds present in tropical peat. This bacterium was isolated by an enrichment
      technique and grew on (+)-catechin as the sole carbon source under acidic
      conditions. The reaction of a crude enzyme extract and a structural study of its
      products showed that (+)-catechin is biotransformed into taxifolin during the
      preliminary stages of its metabolism by KTC-1. HPLC analysis showed that this
      transformation occurs in two oxidation steps: 4-hydroxylation and
      dehydrogenation. Furthermore, both (+)-catechin 4-hydroxylanase and leucocyanidin
      4-dehydrogenase were localized in the cytosol of KTC-1. This is the first report
      on biotransformation of (+)-catechin into taxifolin via leucocyanidin by an
      aerobic bacterium. We suggest that tropical peat could become a unique resource
      for microorganisms that degrade natural aromatic compounds.

PMID- 18068671
TI  - Osteoclasts secrete non-bone derived signals that induce bone formation.
AB  - Bone turnover is a highly regulated process, where bone resorption in the normal
      healthy individual always is followed by bone formation in a manner referred to
      as coupling. Patients with osteopetrosis caused by defective acidification of the
      resorption lacuna have severely decreased resorption, in face of normal or even
      increased bone formation. This suggests that osteoclasts, not their resorptive
      activity, are important for sustaining bone formation. To investigate whether
      osteoclasts mediate control of bone formation by production of bone anabolic
      signals, we collected conditioned media (CM) from human osteoclasts cultured on
      either bone or plastic, and tested their effects on bone nodule formation by
      osteoblasts. Both types of CM were shown to dose-dependently induce bone nodule
      formation, whereas non-conditioned osteoclast culture medium had no effects.
      These data show that osteoclasts secrete non-bone derived factors, which induce
      preosteoblasts to form bone-like nodules, potentially explaining the imbalanced
      coupling seen in osteopetrotic patients.

PMID- 18068672
TI  - Induced expression of death domain genes NALP1 and NALP5 following neuronal
      injury.
AB  - Proteins in apoptotic pathways represent potential points of intervention in
      neurodegenerative disease. We identified several genes of interest that contain
      death domain such as CARD or Pyrin. We found that ASC and NALP10 were
      constitutively expressed in cerebellar neurons. More interestingly, expression
      levels of NALP1 and NALP5 were increased in two neuronal injury models. In
      addition, transient expression of recombinant NALP1 or NALP5 in neurons induced
      caspase-3 activation and apoptosis. These data suggest that NALP1 and NALP5 may
      regulate caspase activation and apoptosis in injured neurons, and thus represent
      novel molecular targets for therapeutic intervention in neurodegenerative
      disorders.

PMID- 18068673
TI  - Connexin 43 contributes to differentiation of retinal pigment epithelial cells
      via cyclic AMP signaling.
AB  - Retinal pigment epithelium (RPE) cells play important roles in the visual system
      that supports neurosensory retina homeostasis. Connexin (Cx) 43-mediated gap
      junctional intercellular communication (GJIC) participates in the regulation of
      retinal organogenesis, but much of the function of Cx43 on the differentiation of
      RPE cells is unclear. Here, we report the involvement of Cx43 in RPE
      differentiation. Knockdown of Cx43 in RPE cells dramatically inhibited the
      differentiation, whereas Cx43-overexpression successfully induced RPE cell
      differentiation under de-differentiation conditions. From the experiments using
      GJIC inhibitors and C-terminus-truncated mutant of Cx43, it was clearly
      demonstrated that the regulation of RPE cell differentiation by Cx43 did not
      result from Cx43-mediated GJIC. The RPE cell differentiation induced by Cx43
      overexpression was abolished by a cAMP antagonist. In contrast, the treatment
      with forskolin and phosphodiesterase inhibitor rolipram induced RPE cell
      differentiation under de-differentiation conditions. These findings indicate that
      Cx43 contributes to RPE differentiation via cAMP signaling.

PMID- 18068674
TI  - Major carboxypeptidase N deficiency.

PMID- 18068675
TI  - A conserved domain of herpes simplex virus ICP34.5 regulates protein phosphatase
      complex in mammalian cells.
AB  - ICP34.5, encoded by herpes simplex virus 1, is a protein phosphatase 1 (PP1)
      regulatory subunit that mediates dephosphorylation of the alpha subunit of
      translation initiation factor 2 (eIF2alpha). However, the mechanism of its action
      remains poorly understood. Here, we show that amino acid substitutions in the
      arginine-rich motif have differential effects on ICP34.5 activity. The phenotypes
      parallel with viral protein synthesis and cytopathic effects in virus infected
      cells. Besides the consensus PP1 binding motif, the Arg-motif appears to enhance
      the interaction between ICP34.5 and PP1. These results suggest that concerted
      action between the PP1 binding domain and the effector domain of ICP34.5 is
      crucial for eIF2alpha dephosphorylation and viral protein synthesis.

PMID- 18068676
TI  - Reciprocal regulation of the human sterol regulatory element binding protein
      (SREBP)-1a promoter by Sp1 and EGR-1 transcription factors.
AB  - Sterol regulatory element binding protein (SREBP)-1a is a transcription factor
      that is highly expressed in actively growing cells, and is involved in the
      biosynthesis of cholesterol, fatty acids and phospholipids. We have mapped the
      minimal human SREBP-1a promoter region to 75bp upstream of the translation start
      site where we discovered a functional role for the 3 GC-boxes containing
      overlapping sites for the Sp1 and EGR-1 transcription factors. Intact SP1-binding
      sites are essential for promoter activity, whereas EGR-1 suppresses the
      transcription of the human SREBP-1a promoter. These results reveal a novel
      physiologically relevant transcriptional mechanism for the reciprocal regulation
      of the SREBP-1a expression.

PMID- 18068677
TI  - Oxidative stress mislocalizes and retains transport factor importin-alpha and
      nucleoporins Nup153 and Nup88 in nuclei where they generate high molecular mass
      complexes.
AB  - Nuclear trafficking of proteins requires the cooperation between soluble
      transport components and nucleoporins. As such, classical nuclear import depends
      on the dimeric carrier importin-alpha/beta1, and CAS, a member of the importin
      beta family, which exports importin-alpha to the cytoplasm. Here we analyzed the
      effect of oxidative stress elicited by diethyl maleate (DEM) on classical nuclear
      transport. Under conditions that do not induce death in the majority of cells,
      DEM has little effect on the nucleocytoplasmic concentration gradient of Ran, but
      interferes with the nuclear accumulation of several reporter proteins. Moreover,
      DEM treatment alters the distribution of soluble transport factors and several
      nucleoporins in growing cells. We identified nuclear retention of importin-alpha,
      CAS as well as nucleoporins Nup153 and Nup88 as a mechanism that contributes to
      the nuclear concentration of these proteins. Both nucleoporins, but not CAS,
      associate with importin-alpha in the nuclei of growing cells and in vitro.
      Importin-alpha generates high molecular mass complexes in the nucleus that
      contain Nup153 and Nup88, whereas CAS was not detected. The formation of high
      molecular mass complexes containing importin-alpha, Nup153 and Nup88 is increased
      upon oxidant treatment, suggesting that complex formation contributes to the
      anchoring of importin-alpha in nuclei. Taken together, our studies link oxidative
      stress to the proper localization of soluble transport factors and nucleoporins
      and to changes in the interactions between these proteins.

PMID- 18068678
TI  - Multimerisation of receptor-type protein tyrosine phosphatases PTPBR7 and PTP-SL
      attenuates enzymatic activity.
AB  - Dimerisation of receptor-type protein tyrosine phosphatases (RPTPs) represents an
      appealing mechanism to regulate their enzymatic activity. Studies thus far mostly
      concern the dimerisation behaviour of RPTPs possessing two tandemly oriented
      catalytic PTP domains. Mouse gene Ptprr encodes four different protein isoforms
      (i.e. PTPBR7, PTP-SL and PTPPBSgamma-42/37) that contain a single PTP domain.
      Using selective membrane permeabilisation we here demonstrate that PTP-SL, like
      PTPBR7, is a single membrane-spanning RPTP. Furthermore, these two receptor-type
      PTPs constitutively formed homo- and hetero-meric complexes as witnessed in
      chemical cross-linking and co-immunoprecipitation experiments, in sharp contrast
      to the cytosolic PTPPBSgamma-42 and PTPPBSgamma-37 PTPRR isoforms. This
      multimerisation occurs independently of the PTP domain and requires the
      transmembrane domain and/or the proximal hydrophobic region. Using overexpression
      of a PTPBR7 mutant that essentially lacks the intracellular PTP domain-containing
      segment, a monomer-mimicking state was forced upon full-length PTPBR7
      immunoprecipitates. This resulted in a significant increase in the enzymatic
      activity of the PTPRR PTP domain, which strengthens the notion that
      multimerisation represents a general mechanism to tone down RPTP catalytic
      activity.

PMID- 18068679
TI  - Molecular mimicry: structural camouflage of proteins and nucleic acids.
AB  - When it comes to protein specificity and function their three-dimensional
      structure is the ultimate determinant. Thus, sequences that participate in key
      parts, such as catalytic sites or DNA binding have been favored and maintained
      highly conserved during evolution. However, in a reversal of fortune, selection
      has favored conservation of shapes over sequence, especially when proteins look
      like nucleic acids. Proteins from pathogens evade the host's defenses because
      they are shaped as DNA; others use such a disguise for transcriptional
      regulation. Several factors are tRNA look-alikes so that they can efficiently
      control the process of protein synthesis. Molecular mimicry among RNAs could
      result in a new unexplored level in gene regulation. This comprehensive review
      outlines this important area and aims to emphasize that molecular mimicry could
      in fact be more widespread than initially thought and eventually adds a new layer
      of genetic regulation.

PMID- 18068680
TI  - Proteolytic enzymes: from structures to transport pathways.

PMID- 18068681
TI  - Ceramide traffic in C6 glioma cells: evidence for CERT-dependent and independent
      transport from ER to the Golgi apparatus.
AB  - Intracellular movements of ceramide are strongly limited by its hydrophobic
      nature, and the mechanisms involved in ceramide transport can represent a crucial
      aspect of sphingolipid metabolism and signaling. The recent identification of the
      ceramide specific carrier protein CERT has revealed a novel pathway for the
      delivery of ceramide to the Golgi apparatus for sphingomyelin biosynthesis. In
      this study we investigated the metabolic and functional role of CERT in C6 glioma
      cells. These cells were found to constitutively express CERT, the protein being
      mainly associated with the cytosolic fraction. Metabolic experiments performed
      with different radioactive metabolic precursors of sphingolipids demonstrated
      that the down regulation of CERT by RNAi technology resulted in a significant but
      not complete reduction of ceramide metabolism to sphingomyelin, without affecting
      its utilization for glycosphingolipid biosynthesis. Since nitric oxide is an
      inhibitor of ceramide ER-to-Golgi traffic and metabolism in C6 glioma cells, we
      evaluated the possibility that the CERT-mediated transport of ceramide might
      represent a target for nitric oxide. The data obtained demonstrate that CERT down
      regulation does not affect the inhibitory activity of nitric oxide on Cer
      metabolism, and the effects of nitric oxide and CERT silencing on ceramide
      utilization were additive. These results strongly suggest that a CERT-mediated
      and a CERT-independent, nitric oxide-sensitive Cer transport coexist in C6 glioma
      cells and can separately contribute to the control of sphingolipid metabolism and
      Cer levels in these cells.

PMID- 18068682
TI  - Isolation and characterization of a new family 42 beta-galactosidase from the
      thermoacidophilic bacterium Alicyclobacillus acidocaldarius: identification of
      the active site residues.
AB  - The thermoacidophilic bacterium Alicyclobacillus acidocaldarius is a rich source
      of glycoside hydrolases enabling its growth on several di- and polysaccharides.
      We report here the purification and the characterization of a beta-galactosidase
      from this source, the cloning of its gene, and the expression and the
      characterization of the recombinant enzyme (Aabeta-gal). The enzyme was purified
      46-fold from A. acidocaldarius extracts; the gene for Aabeta-gal encoded a new
      member of the glycoside hydrolase family 42 (GH42) and it is flanked by a
      putative AraC/XylS regulator, however, the two genes were transcribed
      independently. The recombinant Aabeta-gal was characterized in detail revealing
      that it is optimally active and stable at 65 degrees C. Aabeta-gal is very
      specific for glycosides with an axial C4-OH at their non-reducing end, with
      kcat/KM values of 484, 186, and 332 s(-1) mM(-1) for 2-nitrophenyl-beta-d
      galactoside, -fucoside, and 4-nitrophenyl-alpha-l-arabinoside, respectively.
      Finally, the characterization of the site-directed mutants Glu157Gly and
      Glu313Gly confirmed the latter as the nucleophile of the reaction and gave
      experimental evidence, for the first time in GH42, of the role of Glu157 as the
      acid/base of the catalyzed reaction.

PMID- 18068684
TI  - Differences in transmission seasons as an epidemiological tool for
      characterization of anthroponotic and zoonotic cutaneous leishmaniasis in
      northern Afghanistan.
AB  - Regional epidemiological data, when available from Afghan or international health
      authorities, usually include cutaneous leishmaniasis cases without further
      elaboration. Scientific reports from Afghanistan mainly focus on the current
      status of war and refugee-related anthroponotic cutaneous leishmaniasis (ACL),
      but little is known about zoonotic cutaneous leishmaniasis (ZCL), its regional
      and seasonal distribution, or other disease characteristics. Multiple field
      investigations revealed that both ACL and ZCL are widespread in Afghanistan and
      may show sharp differences in specific epidemiology and incubation periods. The
      previously unknown transmission dynamics and differing seasonality of ZCL, with
      maximum clinical cases in September and October, as opposed to the ACL peak in
      March and April, are here described, thus permitting for the first time
      prediction of the causative Leishmania species in undiscriminated CL reports.
      Results show that epidemiological differences may serve as a convenient tool for
      discriminating between ACL and ZCL, at least in northern and central Afghanistan,
      which can be important because specific treatment and control measures may be
      different.

PMID- 18068683
TI  - Unique MAP Kinase binding sites.
AB  - Map kinases are drug targets for autoimmune disease, cancer, and apoptosis
      related diseases. Drug discovery efforts have developed MAP kinase inhibitors
      directed toward the ATP binding site and neighboring "DFG-out" site, both of
      which are targets for inhibitors of other protein kinases. On the other hand, MAP
      kinases have unique substrate and small molecule binding sites that could serve
      as inhibition sites. The substrate and processing enzyme D-motif binding site is
      present in all MAP kinases, and has many features of a good small molecule
      binding site. Further, the MAP kinase p38alpha has a binding site near its C
      terminus discovered in crystallographic studies. Finally, the MAP kinases ERK2
      and p38alpha have a second substrate binding site, the FXFP binding site that is
      exposed in active ERK2 and the D-motif peptide induced conformation of MAP
      kinases. Crystallographic evidence of these latter two binding sites is
      presented.

PMID- 18068685
TI  - Bionomics of malaria vectors and relationship with malaria transmission and
      epidemiology in three physiographic zones in the Senegal River Basin.
AB  - Following the implementation of two dams in the Senegal River, entomological and
      parasitological studies were conducted in three different ecological zones in the
      Senegal River Basin (the low valley of Senegal River, the Guiers Lake area and
      the low valley of Ferlo) every 3 month in June 2004, September 2004, December
      2004 and March 2005. The objective of this work was to study the influence of
      environmental heterogeneities on vector bionomics and malaria epidemiology.
      Mosquitoes were collected when landing on human volunteers and by pyrethrum spray
      catches. In the parasitological survey, blood samples were taken from a cohort of
      schoolchildren under 9 years during each entomology survey. Seven anopheline
      species were collected: Anopheles arabiensis, Anopheles gambiae M form, Anopheles
      funestus, Anopheles pharoensis, Anopheles coustani, Anopheles wellcomei and
      Anopheles rufipes. A. arabiensis, A. funestus and A. pharoensis were predominant
      in the low valley of the Senegal River, A. funestus in the Guiers Lake area and
      A. arabiensis in the low valley of Ferlo. Mosquito populations' dynamics varied
      temporally depending on the rainy season for each zone. The anthropophilic rates
      varied between 6 and 76% for A. gambiae s.l. and 23 and 80% for A. funestus. Only
      4/396 A. pharoensis and 1/3076 A. funestus tested carried Plasmodium falciparum
      CS antigen. These results suggest the implication of A. pharoensis in malaria
      transmission. The related entomological inoculation rates were estimated to 10.44
      in Mbilor and 3 infected bites in Gankette Balla and were due, respectively, to
      A. pharoensis and A. funestus. Overall, 1636 thick blood smears were tested from
      blood samples taken from schoolchildren with, respectively, a parasite and
      gametocyte average prevalence of 9 and 0.9%. The parasite prevalence was
      uniformly low in Mbilor and Gankette Balla whereas; it increased in September
      (16%) and then remained stable in December and March (22%) in Mboula where
      malaria transmission was not perceptible. However, significant differences were
      observed over time for parasite prevalence in Mbilor and Mboula villages whereas;
      it was only in Gankette Balla village where gametocyte prevalence was
      significantly different over time. Our study demonstrates the influence of
      ecological changes resulted from dams implementation in the Senegal River on the
      composition of vectorial system, malaria transmission and epidemiology. Such
      changes should be thoroughly surveyed in order to prevent any possible malaria
      outbreak in the Senegal River Basin.

PMID- 18068686
TI  - Kinetics of cholesterol extraction from lipid membranes by methyl-beta
      cyclodextrin--a surface plasmon resonance approach.
AB  - The kinetics of cholesterol extraction from cellular membranes is complex and not
      yet completely understood. In this paper we have developed an experimental
      approach to directly monitor the extraction of cholesterol from lipid membranes
      by using surface plasmon resonance and model lipid systems. Methyl-beta
      cyclodextrin was used to selectively remove cholesterol from large unilamellar
      vesicles of various compositions. The amount of extracted cholesterol is highly
      dependent on the composition of lipid membrane, i.e. the presence of
      sphingomyelin drastically reduced and slowed down cholesterol extraction by
      methyl-beta-cyclodextrin. This was confirmed also in the erythrocyte ghosts
      system, where more cholesterol was extracted after erythrocytes were treated with
      sphingomyelinase. We further show that the kinetics of the extraction is mono
      exponential for mixtures of 1,2-dioleoyl-sn-glycero-3-phosphocholine and
      cholesterol. The kinetics is complex for ternary lipid mixtures composed of 1,2
      dioleoyl-sn-glycero-3-phosphocholine, bovine brain sphingomyelin and cholesterol.
      Our results indicate that the complex kinetics observed in experiments with cells
      may be the consequence of lateral segregation of lipids in cell plasma membrane.

PMID- 18068689
TI  - A putative DRD3 schizophrenia risk haplotype deconstructed.

PMID- 18068687
TI  - Differential effects of ABT-510 and a CD36-binding peptide derived from the type
      1 repeats of thrombospondin-1 on fatty acid uptake, nitric oxide signaling, and
      caspase activation in vascular cells.
AB  - ABT-510 is a potent mimetic of an anti-angiogenic sequence from the second type 1
      repeat of thrombospondin-1. ABT-510 and the original d-Ile mimetic from which it
      was derived, GDGV(dI)TRIR, are similarly active for inhibiting vascular outgrowth
      in a B16 melanoma explant assay. Because GDGV(dI)TRIR and thrombospondin-1
      modulate nitric oxide signaling by inhibiting the fatty translocase activity of
      CD36, we examined the ability ABT-510 to modulate fatty acid uptake into vascular
      cells and downstream nitric oxide/cGMP signaling. Remarkably, ABT-510 is less
      active than GDGV(dI)TRIR for inhibiting myristic acid uptake into both
      endothelial and vascular smooth muscle cells. Correspondingly, ABT-510 is less
      potent than GDGV(dI)TRIR for blocking a myristate-stimulated increase in cell
      adhesion to collagen and nitric oxide-driven accumulation of cGMP. ABT-510 at
      concentrations sufficient to inhibit CD36 fatty acid translocase activity
      synergizes with thrombin in aggregating platelets and blunts the activity of NO
      to delay aggregation, but again less than GDGV(dI)TRIR. In contrast, ABT-510 is
      more potent than GDGV(dI)TRIR for inducing caspase activation in vascular cells.
      Thus, we propose that ABT-510 is a drug with at least two mechanisms of action,
      and its potent anti-tumor activity may be in part independent of CD36 fatty acid
      translocase inhibition.

PMID- 18068688
TI  - Expression of cytochrome P450 2A5 in a glucose-6-phosphate dehydrogenase
      deficient mouse model of oxidative stress.
AB  - Murine hepatic cytochrome P450 2A5 (CYP2A5), unlike most CYP enzymes, is
      upregulated during hepatitis and hepatotoxic conditions, but the common stimulus
      for its induction remains unknown. We investigated the involvement of oxidative
      stress in the regulation of CYP2A5 expression using an oxidative stress-sensitive
      glucose-6-phosphate dehydrogenase (G6PD)-deficient mouse model. Treatment of
      deficient and wild-type mice with the prototypical CYP2A5-inducer pyrazole for
      72h led to a significantly greater degree of induction of CYP2A5 mRNA, protein
      and activity in deficient mice, with the greatest increase observed in animals
      homozygous for the deficiency. However, markers of oxidative stress including
      protein carbonyl, 8-hydroxydeoxyguanosine, malondiadehyde and 4-hydroxyalkenal
      levels were unaltered with pyrazole treatment. Furthermore, CYP2A5 expression was
      not altered in G6PD-deficient mice treated with the pro-oxidant menadione whereas
      DNA, lipid, and protein markers of oxidative stress were significantly increased.
      The antioxidant polyethylene glycol-conjugated catalase, while decreasing
      oxidative stress in menadione-treated mice, did not prevent the induction of
      CYP2A5 by pyrazole. Finally, the ER stress marker protein, GRP78, was increased
      following pyrazole treatment in G6PD-deficient compared to wild-type mice. These
      findings do not support a central role for generalized cellular oxidative stress
      in the regulation of CYP2A5 and suggest that additional factors related to G6PD
      deficiency, such as ER stress, may be involved.

PMID- 18068691
TI  - Modulation of extracellular signal-regulated kinase (ERK) by opioid and
      cannabinoid receptors that are expressed in the same cell.
AB  - In the present study we investigated the signal transduction pathways leading to
      the activation of extracellular signal-regulated kinase (ERK) by opioid or
      cannabinoid drugs, when their receptors are coexpressed in the same cell-type. In
      N18TG2 neuroblastoma cells, the opioid agonist etorphine and the cannabinoid
      agonist CP-55940 induced the phosphorylation of ERK by a similar mechanism that
      involved activation of delta-opioid receptors or CB1 cannabinoid receptors
      coupled to Gi/Go proteins, matrix metalloproteases, vascular endothelial growth
      factor (VEGF) receptors and MAPK/ERK kinase (MEK). In HEK-293 cells, these two
      drugs induced the phosphorylation of ERK by separate mechanisms. While CP-55940
      activated ERK by transactivation of VEGFRs, similar to its effect in N18TG2
      cells, the opioid agonist etorphine activated ERK by a mechanism that did not
      involve transactivation of a receptor tyrosine kinase. Interestingly, the
      activation of ERK by etorphine was resistant to the inhibition of MEK, suggesting
      the possible existence of a novel, undescribed yet mechanism for the activation
      of ERK by opioids. This mechanism was found to be specific to etorphine, as
      activation of ERK by the micro-opioid receptor (MOR) agonist DAMGO ([D-Ala(2), N
      Me-Phe(4), Gly(5)-ol] enkephalin) was mediated by MEK in these cells, suggesting
      that etorphine and DAMGO activate distinct, ligand-specific, conformations of
      MOR. The characterization of cannabinoid- and opioid-induced ERK activation in
      these two cell-lines enables future studies into possible interactions between
      these two groups of drugs at the level of MAPK signaling.

PMID- 18068690
TI  - Developmental increases in effective connectivity to brain regions involved in
      phonological processing during tasks with orthographic demands.
AB  - Developmental differences (9- to 15-year-olds) in effective connectivity in left
      hemisphere regions were examined using dynamic causal modeling (DCM) of
      functional magnetic resonance imaging (fMRI) data. Children completed spelling
      tasks in the visual and auditory modalities in which they were asked to determine
      if two words were spelled the same from the first vowel onwards. Intrinsic
      (anatomical) connections were strongest from primary cortical regions to unimodal
      association areas - from Heschl's gyrus to superior temporal gyrus for the
      auditory spelling task and from calcarine to fusiform gyrus for the visual
      spelling task. The modulatory (experimental) effect for the visual spelling task
      from calcarine to superior temporal gyrus was stronger than all other effects
      from calcarine and this effect showed a developmental increase, suggesting
      automatic activation of phonology that increased with age. The modulatory effect
      from Heschl's gyrus to dorsal inferior frontal gyrus also showed a developmental
      increase, suggesting age-related increases in phonological segmentation in verbal
      working memory. All together, these results suggest that there are developmental
      increases in automatic access into brain regions involved in phonological
      processing in tasks that require orthographic processing.

PMID- 18068692
TI  - The structure of an iridoid glycoside, 8-deoxyshanzhiside, from Lamiophlomis
      rotata.
AB  - 8-deoxyshanzhiside was extracted from Lamiophlomis rotata (Benth.) Kudo.
      Extensive NMR spectroscopy techniques were used to fully assign the (1)H and
      (13)C spectra. X-ray investigation was used to identify its conformation, and
      absolute configuration.

PMID- 18068693
TI  - Synthesis of new heterocyclic derivatives of alpha,alpha-trehalose.
AB  - Several novel N-1, N-2, and S-5 tetrazole and 1,3,4-oxadiazole derivatives of
      alpha,alpha-trehalose disubstituted at C-6,6', with potential synthetic and
      pharmacological interest were prepared from commercial tetrazoles and 1,3,4
      oxadiazoles in reaction with hexa-O-benzyl-6,6'-di-O-triflyl-alpha,alpha
      trehalose.

PMID- 18068694
TI  - Synthesis of trans-fused tetrahydrooxepins: stereoselective allylation of sulfur
      or fluoro-substituted tetrahydrooxepins.
AB  - An efficient route to the trans-fused tetrahydrooxepin corresponding to the E
      ring of ciguatoxin was developed. Wide screening of allylation reactions of
      sulfur or fluoro-substituted tetrahydrooxepin revealed that the optimum method
      for obtaining the beta-allylation product selectively was the use of a
      combination of allyltrimethylsilane and TiCl(4) with 6-fluoro-7
      hydroxytetrahydrooxepin.

PMID- 18068695
TI  - Structural characterization of the O-chain polysaccharide of Aeromonas caviae
      ATCC 15468 lipopolysaccharide.
AB  - The O-chain polysaccharide produced by a mild acid degradation of Aeromonas
      caviae ATCC 15468 lipopolysaccharide was found to be composed of L-rhamnose, 2
      acetamido-2-deoxy-D-glucose, 2-acetamido-2-deoxy-D-galactose and phosphoglycerol.
      Subsequent methylation and CE-ESIMS analyses and 1D/2D NMR ((1)H, (13)C and
      (31)P) spectroscopy showed that the O-chain polysaccharide is a high-molecular
      mass acidic branched polymer of tetrasaccharide repeating units with a
      phosphoglycerol substituent having the following structure: [structure: see text]
      where Gro represents glycerol and P represents a phosphate group.

PMID- 18068696
TI  - Discontinuity in the enumeration of sequentially presented auditory and visual
      stimuli.
AB  - The seeking of discontinuity in enumeration was recently renewed because Cowan
      [Cowan, N. (2001). The magical number 4 in short-term memory: A reconsideration
      of mental storage capacity. Behavioral and Brain Sciences, 24, 87-185; Cowan, N.
      (2005). Working memory capacity. Hove: Psychology Press] suggested that it allows
      evaluating the limit of the focus of attention, currently estimated at four
      items. A strong argument in favour of a general constraint of the cognitive
      system is that similar discontinuities should be observed in modalities different
      from the classic simultaneous presentation of visual objects. Recently, data were
      provided on tactile stimuli, but the authors diverged in their conclusion about
      the existence of such discontinuity [Gallace, A., Tan, H. Z., & Spence, C.
      (2006). Numerosity judgments for tactile stimuli distributed over the body
      surface. Perception, 35(2), 247-266; Riggs, K. J., Ferrand, L., Lancelin, D.,
      Fryziel, L., Dumur, G., & Simpson, A. (2006). Subitizing in tactile perception.
      Psychological Science, 17(4), 271-272]. Following a similar rationale, our study
      aimed at evaluating discontinuity in the enumeration of auditory and visual
      stimuli presented sequentially. The clear and similar discontinuity observed in
      error rates, response times and given responses for both modalities favours the
      general capacity limit view, but also questions the size of this capacity,
      because the discontinuity occurred here at size 2. However, the masking of
      stimuli in sensory memory could not be entirely discarded.

PMID- 18068697
TI  - A combinatorial enhancer recognized by Mad, TCF and Brinker first activates then
      represses dpp expression in the posterior spiracles of Drosophila.
AB  - A previous genetic analysis of a reporter gene carrying a 375-bp region from a
      dpp intron (dppMX-lacZ) revealed that the Wingless and Dpp pathways are required
      to activate dpp expression in posterior spiracle formation. Here we report that
      within the dppMX region there is an enhancer with binding sites for TCF and Mad
      that are essential for activating dppMX expression in posterior spiracles. There
      is also a binding site for Brinker likely employed to repress dppMX expression.
      This combinatorial enhancer may be the first identified with the ability to
      integrate temporally distinct positive (TCF and Mad) and negative (Brinker)
      inputs in the same cells. Cuticle studies on a unique dpp mutant lacking this
      enhancer showed that it is required for viability and that the Filzkorper are U
      shaped rather than straight. Together with gene expression data from these
      mutants and from brk mutants, our results suggest that there are two rounds of
      Dpp signaling in posterior spiracle development. The first round is associated
      with dorsal-ventral patterning and is necessary for designating the posterior
      spiracle field. The second is governed by the combinatorial enhancer and begins
      during germ band retraction. The second round appears necessary for proper
      spiracle internal morphology and fusion with the remainder of the tracheal
      system. Intriguingly, several aspects of dpp posterior spiracle expression and
      function are similar to demonstrated roles for Wnt and BMP signaling in proximal
      distal outgrowth of the mammalian embryonic lung.

PMID- 18068699
TI  - colgate/hdac1 Repression of foxd3 expression is required to permit mitfa
      dependent melanogenesis.
AB  - Neural crest-derived pigment cell development has been used extensively to study
      cell fate specification, migration, proliferation, survival and differentiation.
      Many of the genes and regulatory mechanisms required for pigment cell development
      are conserved across vertebrates. The zebrafish mutant colgate (col)/histone
      deacetylase1 (hdac1) has reduced numbers, delayed differentiation and decreased
      migration of neural crest-derived melanophores and their precursors. In
      hdac1(col) mutants normal numbers of premigratory neural crest cells are induced.
      Later, while there is only a slight reduction in the number of neural crest cells
      in hdac1(col) mutants, there is a severe reduction in the number of mitfa
      positive melanoblasts suggesting that hdac1 is required for melanoblast
      specification. Concomitantly, there is a significant increase in and prolonged
      expression of foxd3 in neural crest cells in hdac1(col) mutants. We found that
      partially reducing Foxd3 expression in hdac1(col) mutants rescues mitfa
      expression and the melanophore defects in hdac1(col) mutants. Furthermore, we
      demonstrate the ability of Foxd3 to physically interact at the mitfa promoter.
      Because mitfa is required for melanoblast specification and development, our
      results suggest that hdac1 is normally required to suppress neural crest foxd3
      expression thus de-repressing mitfa resulting in melanogenesis by a subset of
      neural crest-derived cells.

PMID- 18068700
TI  - Pix1 and Pix2 are novel WD40 microtubule-associated proteins that colocalize with
      mitochondria in Xenopus germ plasm and centrosomes in human cells.
AB  - In many animals, the germ line develops from a distinct mitochondria-rich region
      of embryonic cytoplasm called the germ plasm. However, the protein composition of
      germ plasm and its formation remain poorly understood, except in Drosophila.
      Here, we show that Xpat, a recently identified protein component of Xenopus germ
      plasm, interacts via its C-terminal domain with a novel protein, xPix1. Xpat and
      xPix1 are co-expressed in ovaries, eggs and early embryos and colocalize to the
      mitochondrial cloud and germ plasm in stage I and stage VI oocytes, respectively.
      Although Xpat appears unique to Xenopus, Pix proteins, which contain an N
      terminal WD40 domain and C-terminal coiled-coil, are widely conserved. In humans,
      two proteins, Pix1 and Pix2, are expressed at varying levels in different cancer
      cell lines. Importantly, as well as localizing to mitochondria, human Pix
      proteins localize to centrosomes and associate with microtubules in vitro and in
      vivo. Although, Pix proteins are stably expressed through the cell cycle, Pix2
      concentrates on microtubule structures in mitosis and microinjection of Pix
      antibodies interferes with cell division. Based on these data, we propose that
      Pix1 and Pix2 are microtubule-associated adaptor proteins that likely contribute
      to a range of developmental and cell division processes.

PMID- 18068701
TI  - Characterization of lipid metabolism in insulin-sensitive adipocytes
      differentiated from immortalized human mesenchymal stem cells.
AB  - There is a great demand for cell models to study human adipocyte function. Here
      we describe the adipogenic differentiation of a telomerase-immortalized human
      mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of
      terminally differentiated adipocytes even after prolonged withdrawal of the
      peroxisome proliferator activated receptor gamma (PPARgamma) agonist
      rosiglitazone. Differentiated hMSC-Tert developed the characteristic monolocular
      phenotype of mature adipocytes. The expression of adipocyte specific markers was
      highly increased during differentiation. Most importantly, the presence of the
      PPARgamma agonist rosiglitazone was not required for the stable expression of
      lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA
      and protein levels. Adiponectin expression was post-transcriptionally down
      regulated in the absence of rosiglitazone. Insulin sensitivity as measured by
      insulin-induced phosphorylation of Akt and S6 ribosomal protein was also
      independent of rosiglitazone. In addition to commonly used adipogenic markers, we
      investigated further PPARgamma-stimulated proteins with a role in lipid
      metabolism. We observed an increase of lipoprotein receptor (VLDLR, LRP1) and
      apolipoprotein E expression during differentiation. Despite this increased
      expression, the receptor-mediated endocytosis of lipoproteins was decreased in
      differentiated adipocytes, suggesting that these proteins may have an additional
      function in adipose tissue beyond lipoprotein uptake.

PMID- 18068698
TI  - The Hedgehog gene family of the cnidarian, Nematostella vectensis, and
      implications for understanding metazoan Hedgehog pathway evolution.
AB  - Hedgehog signaling is an important component of cell-cell communication during
      bilaterian development, and abnormal Hedgehog signaling contributes to disease
      and birth defects. Hedgehog genes are composed of a ligand ("hedge") domain and
      an autocatalytic intein ("hog") domain. Hedgehog (hh) ligands bind to a conserved
      set of receptors and activate downstream signal transduction pathways terminating
      with Gli/Ci transcription factors. We have identified five intein-containing
      genes in the anthozoan cnidarian Nematostella vectensis, two of which (NvHh1 and
      NvHh2) contain definitive hedgehog ligand domains, suggesting that to date,
      cnidarians are the earliest branching metazoan phylum to possess definitive Hh
      orthologs. Expression analysis of NvHh1 and NvHh2, the receptor NvPatched, and a
      downstream transcription factor NvGli (a Gli3/Ci ortholog) indicate that these
      genes may have conserved roles in planar and trans-epithelial signaling during
      gut and germline development, while the three remaining intein-containing genes
      (NvHint1,2,3) are expressed in a cell-type-specific manner in putative neural
      precursors. Metazoan intein-containing genes that lack a hh ligand domain have
      previously only been identified within nematodes. However, we have identified
      intein-containing genes from both Nematostella and in two newly annotated
      lophotrochozoan genomes. Phylogenetic analyses suggest that while nematode
      inteins may be derived from an ancestral true hedgehog gene, the newly identified
      cnidarian and lophotrochozoan inteins may be orthologous, suggesting that both
      true hedgehog and hint genes may have been present in the cnidarian-bilaterian
      ancestor. Genomic surveys of N. vectensis suggest that most of the components of
      both protostome and deuterostome Hh signaling pathways are present in anthozoans
      and that some appear to have been lost in ecdysozoan lineages. Cnidarians possess
      many bilaterian cell-cell signaling pathways (Wnt, TGFbeta, FGF, and Hh) that
      appear to act in concert to pattern tissues along the oral-aboral axis of the
      polyp. Cnidarians represent a diverse group of animals with a predominantly
      epithelial body plan, and perhaps selective pressures to pattern epithelia
      resulted in the ontogeny of the hedgehog pathway in the common ancestor of the
      Cnidaria and Bilateria.

PMID- 18068702
TI  - A novel method for generating corneal haze in anterior stroma of the mouse eye
      with the excimer laser.
AB  - Refractive surgery is a popular method used to reduce or eliminate dependence on
      glasses and contact lenses. Corneal haze is one of the common complications
      observed after photorefractive keratectmomy (PRK). The objective of this study
      was to develop an in vivo mouse model that consistently produces moderate to
      severe corneal haze in the anterior stroma of the mouse cornea after excimer
      laser treatment to study myofibroblast biology and corneal wound healing in a
      genetically defined model. Regular- or irregular-phototherapeutic keratectomy
      (PTK) was performed on black C57BL/6 mice with the Summit Apex excimer laser
      (Alcon, Ft. Worth, TX). Different numbers of laser pulses (45; ablation depth
      approximately 10 microm) were fired on the central cornea, after scraping the
      epithelium prior to excimer laser ablation. Irregularity was generated by
      positioning a fine mesh screen in the path of laser after firing 50% of the
      pulses. Eyes were collected 1, 2, 3 or 4 weeks after the procedure. Haze
      formation was gauged with slit lamp biomicroscopy. Immunocytochemistry was used
      to determine number of myofibroblasts in the mouse cornea using antibodies
      specific for the myofibroblast marker alpha-smooth muscle actin (SMA). The
      numbers of SMA-positive cells/400x microscopic were determined by counting within
      the stroma. Statistical analysis was performed using analysis of variance (AVOVA)
      with the Bonferonni-Dunn adjustment for repeated measures. Regular-PTK with
      epithelial scrape (group 3) and irregular-PTK with epithelial scrape (group 4) in
      the mouse eyes were performed to produce corneal haze. Eyes collected 4 weeks
      after regular- or irregular-PTK after epithelial scrape showed 22+/-6.6 (group 3)
      or 34+/-7.9 (group 4) SMA-positive cells in the anterior cornea. The difference
      in the SMA-positive cells detected among the groups was statistically significant
      (p<0.01). Less than 4 SMA-positive cells were detected in the tissue sections of
      the mouse eyes collected after 1, 2 or 3 weeks of regular (group 3) or irregular
      PTK (group 4) or controls (groups 1 and 2). The optimized PTK excimer laser
      conditions developed in this study produces haze selectively in anterior stroma
      of the mouse cornea immediately beneath the epithelial basement membrane.
      Irregular PTK performed after epithelial scrape by applying 45 laser pulses was
      found to be the most effective method to generate myofibroblasts. This PTK
      technique for inducing haze in mouse cornea in vivo provides a useful model for
      studying wound healing and myofibroblast biology in transgenic mice.

PMID- 18068703
TI  - Hypermethylation of CpG island loci of multiple tumor suppressor genes in
      retinoblastoma.
AB  - Epigenetic silencing of tumor suppressor genes by methylation of discrete regions
      of the CpG islands is a major mechanism underlying tumorigenesis. Methylation of
      at least three of five specific genes may represent a distinct trait, termed the
      CpG island methylator phenotype (CIMP). Positive CIMP is associated with BRAF
      mutations. The present study sought to investigate the presence of BRAF mutations
      in human retinoblastoma and the role of epigenetic silencing of multiple tumor
      suppression genes in a search for methylation phenotype. Twenty-five archival
      retinoblastoma samples were analyzed for BRAF mutations with polymerase chain
      reaction, Mutector assay, and direct sequencing. Nineteen samples were also
      analyzed for the promoter methylation status of eight candidate cancer-related
      genes using real-time quantitative methylation-specific polymerase chain reaction
      after sodium bisulfite modification. The CIMP status was determined. No BRAF
      mutations were found. The frequencies of cancer-related gene methylation were as
      follows: 89% for RASSF1A, 52% for NEUROG1, 5% for DAP-kinase, RUNX3 and CACNA1G,
      and 0 for RAR-beta2, SOCS-1 and IGF-2. The lack of BRAF mutations in
      retinoblastoma is in accord with the negative CIMP status and the high
      hypermethylation rate for RASSF1A. The high methylation status for NEUROG1 may
      point to an alternative pathway in the development and progression of
      retinoblastoma, but further studies are needed.

PMID- 18068704
TI  - Focus on molecules: optineurin.

PMID- 18068705
TI  - Prevention of selenite-induced cataractogenesis in Wistar rats by the polyphenol,
      ellagic acid.
AB  - The present study sought to evaluate the efficacy of the naturally-occurring
      polyphenol, ellagic acid, in preventing selenite-induced cataractogenesis. In the
      present study, Wistar rat pups were divided into 3 groups of 15 each. Group I
      (normal) rats received an intraperitoneal (i.p.) injection of normal saline on
      postpartum day 10; group II (cataract-untreated) rats received a single
      subcutaneous (s.c.) injection of sodium selenite (19 micromol/kg body weight) on
      postpartum day 10; group III (cataract-treated) pups received a single s.c.
      injection of sodium selenite on postpartum day 10 and intraperitoneal injections
      of ellagic acid (200mg/kg body weight) on postpartum days 9-14. At the end of the
      study period (30th postpartum day), slit-lamp examination of both eyes of each
      rat pup revealed no lenticular opacification (cataract stage 0) in all eyes of
      group I pups, definite nuclear cataracts (stages 4-6) in the eyes of all (100%)
      group II rat pups and no lenticular opacification in eight (53%) and mild
      lenticular opacification (cataract stages 1-3) in seven (47%) of group III rats
      (changes in group II vs group III, P<0.01). The mean activities of the
      antioxidant enzymes catalase, glutathione peroxidase, superoxide dismutase and
      glutathione-S-transferase were significantly lower in lenses of Group II rats
      than in Group I or Group III rat lenses. In addition, the mean levels of GSH in
      lenses and erythrocytes were also significantly lower in Group II rats than in
      Group I or Group III rats. Conversely, the mean concentration of MDA (an
      indicator of lipid peroxidation) in lenses and erythrocytes was found to be
      significantly higher in Group II rats than that in Group I or Group III rats.
      Also, the mean concentration of calcium was found to be significantly higher in
      lenses of Group II rats than in those of Group I and Group III rats. The results
      suggest that ellagic acid can prevent or retard experimental selenite-induced
      cataractogenesis in Wistar rats. This protective effect in rat lenses appears to
      occur by maintaining the antioxidant defense system and inhibition of lipid
      peroxidation.

PMID- 18068706
TI  - Is dihydrolipoic acid among the reductive activators of parasite CysHis
      proteases?
AB  - Activities of mature CysHis proteases depend upon relative rates of oxidations
      vs. reductions of catalytic sulfur by multiple enzymatic and non-enzymatic
      reactions. CysHis peptidolysis is inhibited by Fe3+ but not Fe2+. Others report
      the paradox that malarial parasites require exogenous free lipoic acid (LA) from
      human host, although the apicoplast organelle produces it. Extra-cellular LA
      disulfide can be taken up and reduced to dihydrolipoic acid (DHLA) by reductases
      of any cell type. Here, the opposing effects of DHLA vs. Fe3+ on the falcipain-2
      hemoglobinase were investigated employing Z-Phe-Arg-AMC substrate. Despite
      limited solubility, non-regenerated DHLA (10 microM, threshold 2 microM) was
      found to be the most potent activator of the air-inactivated (sulfoxygenated)
      protease discovered thus far. Activation was preemptively opposed by Fe3+, but
      not Fe2+. However, cruzain from T. cruzi, and cathepsin B from mammal were
      indistinguishable in their responsiveness to DHLA and Fe redox. Thus, DHLA
      activation vs. Fe3+ inhibition is not unique to falcipain-2 or apicomplexans but
      is rather a primordial feature of CysHis peptidolysis. Free LA and/or
      unassociated lipoylated enzyme subunits could be among multiple pathways
      shuttling reducing equivalents to reduction of proteins, including CysHis
      proteases. It is discussed that opposing DHLA-Fe3+ modification of plasmodial
      proteolysis might be a specialized adaptation to intra-erythrocytic growth.

PMID- 18068707
TI  - Variation with semilunar periodicity of plasma steroid hormone production in the
      mudskipper Boleophthalmus pectinirostris.
AB  - Variation in the production of the plasma steroid hormones E(2), 17alpha-OHP and
      T in females and T and 11-KT in males, was investigated in the mudskipper
      Boleophthalmus pectinirostris during the spawning season. Females with oocytes at
      the vitellogenic stage (GSI 5.97-6.86%) and mature males with GSI of 0.255-0.288%
      were collected at intervals of 3-4 days within the two complete semilunar cycles
      from May 31 to June 30, 2006. The results showed that variations in the levels of
      plasma steroid hormones were synchronized obviously with semilunar periodicity in
      both females and males. Each steroid hormone level exhibited two cycles, each
      cycle with a peak. In females, the first peaks in plasma E(2), 17alpha-OHP and T
      levels were observed 3 days after the first lunar quarter, and the second ones, 4
      days after the last lunar quarter. In males, the first peaks of plasma T and 11
      KT levels occurred 3 days after the first lunar quarter, and the second ones, at
      the last lunar quarter. The fact that, in the present study, changes in the
      levels of plasma steroid hormones were synchronized with semilunar periodicity,
      although the fish were at the same stages of gonadal development, suggests that
      variation of plasma steroid hormones is basically regulated by biological rhythms
      (Zeitgebers), and that tidal movement (with its semilunar periodicity) is the
      major environmental factor stimulating steroid hormone production in B.
      pectinirostris.

PMID- 18068709
TI  - Monocyte function rather than number is a prerequisite for the stimulation of
      collateral growth.

PMID- 18068708
TI  - NK cell apoptosis in coronary artery disease: relation to oxidative stress.
AB  - OBJECTIVE: Natural killer (NK) cells, key elements in initiation and modulation
      of immune responses, were recently found to be reduced in coronary artery disease
      (CAD). To clarify mechanisms behind this reduction, we here investigated NK cell
      apoptosis in CAD patients. Since oxidative stress has been linked to NK cell
      apoptosis, we related the findings to oxidative stress in vivo and evaluated the
      ex vivo susceptibility of NK cells to oxidized lipids. METHODS AND RESULTS: The
      number of apoptotic NK cells in peripheral blood was significantly increased in
      CAD patients compared to controls. Purified NK cells from CAD patients also
      showed a higher rate of spontaneous apoptosis ex vivo. Dose- and time-dependent
      effects of oxidized LDL and 7beta-hydroxycholesterol (7betaOH) on apoptosis and
      ROS production were determined in NK cells from blood donors. Thereafter,
      purified NK cells from CAD patients and healthy controls were exposed to the
      oxidized lipids in a paired design. NK cells from patients were more susceptible
      to apoptosis induced by oxidized LDL, in particular 7betaOH, compared to cells
      from controls. Plasma measurements of LDL protein oxidation and lipid
      peroxidation did not show any differences between patients and controls. On the
      other hand, plasma carotenoids were significantly decreased in patients and
      inversely correlated to NK cell apoptosis rate. CONCLUSION: The rate of
      spontaneous NK cell apoptosis was increased in CAD patients. Although NK cells in
      CAD patients were more sensitive to oxidized lipids ex vivo, indicating a
      mechanism contributing to the reduced NK cell activity in CAD, the data could not
      verify an obvious link between NK cell apoptosis and increased oxidative stress
      in vivo.

PMID- 18068710
TI  - Greater toe grip and gentler heel strike are the strategies to adapt to slippery
      surface.
AB  - This study investigated the plantar pressure distribution during gait on wooden
      surface with different slipperiness in the presence of contaminants. Fifteen
      Chinese males performed 10 walking trials on a 5-m wooden walkway wearing cloth
      shoe in four contaminated conditions (dry, sand, water, oil). A pressure insole
      system was employed to record the plantar pressure data at 50Hz. Peak pressure
      and time-normalized pressure-time integral were evaluated in nine regions. In
      comparing walking on slippery to non-slippery surfaces, results showed a 30%
      increase of peak pressure beneath the hallux (from 195.6 to 254.1kPa), with a
      dramatic 79% increase in the pressure time integral beneath the hallux (from 63.8
      to 114.3kPa) and a 34% increase beneath the lateral toes (from 35.1 to 47.2kPa).
      In addition, the peak pressure beneath the medial and lateral heel showed
      significant 20-24% reductions, respectively (from 233.6-253.5 to 204.0-219.0kPa).
      These findings suggested that greater toe grip and gentler heel strike are the
      strategies to adapt to slippery surface. Such strategies plantarflexed the ankle
      and the metatarsals to achieve a flat foot contact with the ground, especially at
      heel strike, in order to shift the ground reaction force to a more vertical
      direction. As the vertical ground reaction force component increased, the
      available ground friction increased and the floor became less slippery.
      Therefore, human could walk without slip on slippery surfaces with greater toe
      grip and gentler heel strike as adaptation strategies.

PMID- 18068712
TI  - Application of single-drop microextraction combined with in-microvial
      derivatization for determination of acidic herbicides in water samples by gas
      chromatography-mass spectrometry.
AB  - A single-drop microextraction (SDME) method and gas chromatography with mass
      spectrometry detection have been developed for the determination of acidic
      herbicides in water. The analytes were extracted from a 3 mL sample solution
      using 4 microL of hexyl acetate. After extraction, derivatization was carried out
      inside a glass microvial (1.1mm i.d.) using pentafluorobenzyl bromide (PFBBr).
      Triethylamine (TEA) was used as the reaction catalyst. The influence of
      derivatization reagent volume, catalyst amount, derivatization time and
      temperature on the yield of the in-microvial derivatization was investigated.
      Derivatization reaction was performed using 0.3 microL of PFBBr and 0.4 microL of
      TEA (10%, v/v in toluene) at 100 degrees C during 5 min. Also, the effects of
      different experimental SDME parameters such as selection of organic solvent,
      sample pH, addition of salt, extraction time and temperature of extraction were
      studied. Analytical parameters such as enrichment factor, precision, linearity
      and detection limits were also determined. The enrichment factors were between 83
      and 157. The limits of detection (LOD) were in the range 1.2-7 ng/L (S/N=3). The
      relative standard deviations obtained were below 10.1% (n=5).

PMID- 18068713
TI  - Editorial on "Non-covalent capillary coatings for protein separations in
      capillary electrophoresis" by C.A. Lucy, A.M. MacDonald and M.D. Gulcev.

PMID- 18068714
TI  - High-performance liquid chromatographic evaluation of a coated cellulose tris(3,5
      dimethylphenylcarbamate) chiral stationary phase having a small-pore silica
      support.
AB  - A two-step coating/precipitation synthetic procedure has been developed for the
      preparation of cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary
      phase (CSP) having a small-pore silica support. With this synthetic strategy,
      monodisperse, spherical CSP particles can be produced without the need for a
      wasteful and time-consuming sieving process. The performance of the synthesized
      CSP towards a variety of racemates was evaluated in the normal-phase HPLC mode.
      HPLC separation experiments revealed that the synthesized CSP exhibited a chiral
      recognition ability fully comparable to the corresponding commercial columns
      prepared using conventional large-pore silica as the support. Moreover, the
      synthesized CSP was successfully applied to semipreparative enantioseparation of
      a new triazole antifungal agent.

PMID- 18068715
TI  - Thermoresponsive polymer-stabilized silver nanoparticles.
AB  - Silver nanoparticles (Ag NPs) stabilized by a thermoresponsive polymer, poly(N
      isopropylacrylamide) (PNIPAM), have been synthesized by the reduction of silver
      ions with NaBH(4) in aqueous solutions. The obtained Ag NPs are very stable at
      room temperature due to the extended coil conformation of the PNIPAM chain at
      temperatures below its volume phase transition temperature ( approximately 32
      degrees C). At higher temperatures (such as 45 degrees C) above the phase
      transition of PNIPAM, only minute aggregation between Ag NPs was observed,
      showing that the collapsed PNIPAM chains still retain the ability to stabilize Ag
      NPs. The PNIPAM-stabilized Ag NPs were then characterized as a function of the
      thermal phase transition of PNIPAM by UV-vis spectroscopy, dynamic light
      scattering, transmission electron microscopy, and cyclic voltammeter. Consistent
      results were obtained showing that the phase transition of PNIPAM has some effect
      on the optical properties of Ag NPs. Switchable electrochemical response of the
      PNIPAM-stabilized Ag NPs triggered by temperature change was observed.

PMID- 18068716
TI  - Development of porosity in carbons from yeast grains by activation with alkali
      metal carbonates.
AB  - Cellular structured activated carbon samples were prepared with the aid of alkali
      carbonates X2CO3 (X = Li, Na, K, Rb, or Cs) from dry bread yeast with a milling
      procedure. The resultant carbon possesses a very large adsorption amount even for
      supercritical methane. The activation with Cs2CO3 gave the greatest surface area
      of 2420 m2 g(-1) from the subtracting pore effect method. The activation
      efficiency of X2CO3 (X = Li, Na, K, Rb, and Cs) was associated with the order of
      Gibbs free energy of X2O (X = Li, Na, K, Rb, and Cs) which should play an
      important role in the gasification. The carbon activated with Rb2CO3 gave the
      greatest adsorption amount of supercritical methane of 90 mg g(-1) at 0.9 MPa at
      303 K.

PMID- 18068717
TI  - An improved process for separation of proteins using modified chitosan-silica
      cross-linked charged ultrafilter membranes under coupled driving forces:
      isoelectric separation of proteins.
AB  - Functionalized chitosan namely as N-methylene phosphonic chitosan (PC) and
      quaternized chitosan (QC) silica composite charged ultrafilter membranes were
      prepared by acid catalyzed sol-gel method in the aqueous media and gelated in
      methanol for tailoring their pore structure. These membranes were employed for
      developing a simple membrane process for pH sensitive protein fractionation under
      coupled driving forces (pressure and electric gradient). Protein transmission
      (selectivity) and membrane throughput across both membranes were studied using
      binary mixture of protein under different gradients at pH points: 2.0, 4.8, 10.7,
      and 13.0. It was concluded that separation from the binary mixture of BSA-LYS,
      separation LYS at pH 4.8 (pI of BSA) using negatively charged PC-Si membrane or
      separation BSA at pH 10.7 (pI of LYS) using positively charged QC-Si membrane,
      was possible with high selectivity. Also in all cases, due to coupling of driving
      forces, filtrate flux and selectivity were enhanced by several folds.
      Furthermore, applied electric gradient progressively increased the separation
      factor values, which was close to 10 for PC-Si and 15 for QC-Si membranes.
      Relatively high separation value of individual protein from binary mixture and
      filtrate velocity suggests the practical usefulness of this novel process and
      biopolymer membranes.

PMID- 18068718
TI  - Temperature and compression rate independent domain shape in Langmuir monolayers
      of di-n-dodecyl hydrogen phosphate at the air-water interface.
AB  - Thermodynamic and morphological properties of Langmuir monolayers of di-n-dodecyl
      hydrogen phosphate (DDP) have been studied by film balance and Brewster angle
      microscopy (BAM) over a wide range of temperature between 5 and 40 degrees C.
      From pi-A isotherms, a generalized phase diagram consisting of gas (G), liquid
      expanded (LE) and liquid condensed (LC) phases is constructed for the DDP
      monolayers. The BAM images show the formation of gas bubble in the bright
      background of LE phase during G-LE phase transitions and fingering LC domains
      during LE-LC phase transitions. The shapes of these domains are independent of
      temperature, showing a sharp contrast to the temperature-dependent monolayer
      morphologies of amphiphilic systems where the shape of the LC domains changes
      either from compact circular to fingering or from irregular or spiral to compact
      patterns with increasing temperature. In addition, the domains do not show any
      change in their shapes with decreasing the compression rate. Since the two-alkyl
      chains are directly attached by covalent bonds to the phosphate group, the
      rearrangement of the molecules needs to move the whole molecules including the
      hydration sphere. The difficulty related to such a movement of the molecules
      causes the fingering domains, which are independent of external variables.
      Although the domains are formed in a fingering shape, the equilibrium shape can
      be attained by about 120 min at 15 degrees C indicating a rather slow relaxation
      rate.

PMID- 18068719
TI  - Prediction of permeate flux during osmotic pressure-controlled electric field
      enhanced cross-flow ultrafiltration.
AB  - Electric field-enhanced cross-flow ultrafiltration has been carried out to
      separate protein, bovine serum albumin, from aqueous solution using a 30,000
      molecular weight cutoff membrane. A theoretical model is developed to predict
      permeate flux under a laminar flow regime including the effects of external d.c.
      electric field and suction through the membrane for osmotic pressure-controlled
      ultrafiltration. The governing equations of the concentration profile in the
      developing mass transfer boundary layer in a rectangular channel are solved using
      a similarity solution method. The effect of d.c. electric field on the variation
      of membrane surface concentration and permeate flux along the length of the
      channel is quantified using this model. The expression of Sherwood number
      relation for estimation of mass transfer coefficient is derived. The analysis
      revealed that there is a significant effect of electric field on the mass
      transfer coefficient. A detailed parametric study has been carried out to observe
      the effect of feed concentration, electric field, cross-flow velocity, and
      pressure on the permeate flux. For 1 kg/m3 BSA solution, by applying a d.c.
      electric field of 1000 V/m, the permeate flux increases from 42 to 98 L/m2 h
      compared to that with zero electric field. The experimental results are
      successfully compared with the model predicted results.

PMID- 18068720
TI  - The effect of mating on immunity can be masked by experimental piercing in female
      Drosophila melanogaster.
AB  - Mating and immunity are two major components of fitness and links between them
      have been demonstrated in a number of recent investigations. In Drosophila
      melanogaster, a seminal fluid protein, sex-peptide (SP), up-regulates a number of
      antimicrobial peptide (AMP) genes in females after mating but the resulting
      effect on pathogen resistance is unclear. In this study, we tested (1) whether SP
      induced changes in gene expression affect the ability of females to kill injected
      non-pathogenic bacteria and (2) how the injection process per se affects the
      expression of AMP genes relative to SP. The ability of virgin females and females
      mated to SP lacking or control males to clear bacteria was assayed using an
      established technique in which Escherichia coli are injected directly into the
      fly body and the rate of clearance of the injected bacteria is determined. We
      found no repeatable differences in clearance rates between virgin females and
      females mated to SP producing or SP lacking males. However, we found that the
      piercing of the integument, as occurs during injection, up-regulates AMP gene
      expression much more strongly than SP. Thus, assays that involve piercing, which
      are commonly used in immunity studies, can mask more subtle and biologically
      relevant changes in immunity, such as those induced by mating.

PMID- 18068721
TI  - A beta-hairpin comprising the nuclear localization sequence sustains the self
      associated states of nucleosome assembly protein 1.
AB  - The histone chaperone nucleosome assembly protein 1 (NAP1) is implicated in
      histone shuttling as well as nucleosome assembly and disassembly. Under
      physiological conditions, NAP1 dimers exist in a mixture of various high
      molecular-weight oligomers whose size may be regulated by the cell cycle
      dependent concentration of NAP1. Both the functional and structural significance
      of the observed oligomers are unknown. We have resolved the molecular mechanism
      by which yeast NAP1 (yNAP1) dimers oligomerize by applying x-ray
      crystallographic, hydrodynamic, and functional approaches. We found that an
      extended beta-hairpin that protrudes from the compact core of the yNAP1 dimer
      forms a stable beta-sheet with beta-hairpins of neighboring yNAP1 dimers.
      Disruption of the beta-hairpin (whose sequence is conserved among NAP1 proteins
      in various species) by the replacement of one or more amino acids with proline
      results in complete loss of yNAP1 dimer oligomerization. The in vitro functions
      of yNAP1 remain unaffected by the mutations. We have thus identified a conserved
      structural feature of NAP1 whose function, in addition to presenting the nuclear
      localization sequence, appears to be the formation of higher-order oligomers.

PMID- 18068723
TI  - A new cryo-EM single-particle ab initio reconstruction method visualizes
      secondary structure elements in an ATP-fueled AAA+ motor.
AB  - The generation of ab initio three-dimensional (3D) models is a bottleneck in the
      studies of large macromolecular assemblies by single-particle cryo-electron
      microscopy. We describe here a novel method, in which established methods for two
      dimensional image processing are combined with newly developed programs for joint
      rotational 3D alignment of a large number of class averages (RAD) and calculation
      of 3D volumes from aligned projections (VolRec). We demonstrate the power of the
      method by reconstructing an approximately 660-kDa ATP-fueled AAA+ motor to 7.5 A
      resolution, with secondary structure elements identified throughout the
      structure. We propose the method as a generally applicable automated strategy to
      obtain 3D reconstructions from unstained single particles imaged in vitreous ice.

PMID- 18068722
TI  - Characterization of a novel prokaryotic GDP dissociation inhibitor domain from
      the G protein coupled membrane protein FeoB.
AB  - The FeoB family of membrane embedded G proteins are involved with high affinity
      Fe(II) uptake in prokaryotes. Here, we report that FeoB harbors a novel GDP
      dissociation inhibitor-like domain that specifically stabilizes GDP-binding
      through an interaction with the switch I region of the G protein. We show that
      the stabilization of GDP binding is conserved between species despite a high
      degree of sequence variability in their guanine nucleotide dissociation inhibitor
      (GDI)-like domains, and demonstrate that the presence of the membrane embedded
      domain increases GDP-binding affinity roughly 150-fold over the level
      accomplished by action of the GDI-like domain alone. To our knowledge, this is
      the first example for a prokaryotic GDI, targeting a bacterial G protein-coupled
      membrane process. Our findings suggest that Fe(II) uptake in bacteria involves a
      G protein regulatory pathway reminiscent of signaling mechanisms found in higher
      order organisms.

PMID- 18068725
TI  - Probing reward function in posttraumatic stress disorder: expectancy and
      satisfaction with monetary gains and losses.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) may be associated with
      dysfunctional reward processing. The present study assessed for such dysfunction
      in both the expectancy and outcome phases of reward processing. METHODS: Male
      Vietnam veterans with (n=15) and without (n=11) combat-related PTSD were
      administered a wheel of fortune-type gambling task. Self-reported ratings of
      expectancy and satisfaction were collected respectively before and after each
      experience of monetary gain or loss. RESULTS: PTSD participants reported both
      lower expectancy of reward and lower satisfaction with reward when it was
      received. The latter result was manifest in a failure of PTSD participants to
      show the greater satisfaction that normally accompanies rewards received under
      conditions of low expectancy. CONCLUSION: These results suggest reward function
      impairment in PTSD related to expectancy, satisfaction, and the expectancy
      satisfaction relationship.

PMID- 18068724
TI  - Structure of antibody F425-B4e8 in complex with a V3 peptide reveals a new
      binding mode for HIV-1 neutralization.
AB  - F425-B4e8 (B4e8) is a monoclonal antibody isolated from a human immunodeficiency
      virus type 1 (HIV-1)-infected individual that recognizes the V3 variable loop on
      the gp120 subunit of the viral envelope spike. B4e8 neutralizes a subset of HIV-1
      primary isolates from subtypes B, C and D, which places this antibody among the
      very few human anti-V3 antibodies with notable cross-neutralizing activity. Here,
      the crystal structure of the B4e8 Fab' fragment in complex with a 24-mer V3
      peptide (RP142) at 2.8 A resolution is described. The complex structure reveals
      that the antibody recognizes a novel V3 loop conformation, featuring a five
      residue alpha-turn around the conserved GPGRA apex of the beta-hairpin loop. In
      agreement with previous mutagenesis analyses, the Fab' interacts primarily with
      V3 through side-chain contacts with just two residues, Ile(P309) and Arg(P315),
      while the remaining contacts are to the main chain. The structure helps explain
      how B4e8 can tolerate a certain degree of sequence variation within V3 and,
      hence, is able to neutralize an appreciable number of different HIV-1 isolates.

PMID- 18068726
TI  - Whole brain diffusion tensor imaging histogram analysis in vascular cognitive
      impairment.
AB  - BACKGROUND: Studies were carried out to detect brain tissue damage in patients
      with vascular cognitive impairment (VCI) using diffusion tensor imaging (DTI)
      histogram analysis, and to determine the correlations between DTI histogram
      derived measures and Mini-Mental State Examination (MMSE) scores. METHODS:
      Conventional MRI and DTI scans were performed on 19 patients with VCI, 19 age-
      and sex-matched post-stroke patients without cognitive impairment (stroke group)
      and 19 cognitively normal subjects (CN group). Histograms of the apparent
      diffusion coefficient (ADC) and fractional anisotropy (FA) of the whole brain
      were analyzed. RESULTS: Analysis showed that the patterns of the whole brain ADC
      and FA histograms of the VCI group differed from those of the stroke and CN
      groups. Compared with those of the two control groups, the mean FA value was
      significantly lower and the FA histogram peak height was higher in the VCI group.
      However, the patterns of the whole brain ADC and FA histograms in the stroke
      group were similar to those of the CN group, and there were no significant
      differences in any of the DTI histogram-derived measures between these two
      groups. The mean FA value, the FA histogram peak height, and the FA histogram
      peak location in VCI patients correlated with the MMSE scores. CONCLUSIONS: Our
      findings suggest that VCI leads to abnormal diffusion in brain tissue, and that
      DTI histogram-derived measures might be used to monitor the severity of cognitive
      impairment in this disease.

PMID- 18068727
TI  - Diastolic ventricular aspiration: a mechanism supporting the rapid filling phase
      of the human ventricles.
AB  - During the rapid filling phase of the heart cycle, the internal volumes of the
      two ventricular cavities approximately double, while the intraventricular
      pressures rise typically only by an amount of less than 1 kPa. Such a small
      pressure increase cannot be the sole driving mechanism for the large inflow of
      blood associated with ventricular expansion during this period. Instead, the
      rapid filling phase is to be interpreted as being mediated primarily by the heart
      recoiling elastically from its contracted state, causing blood to be aspirated
      rapidly into the ventricles. In order to study the role of this mechanism,
      elastic finite element (FE) simulations of ventricular expansion were performed,
      taking into account the large deformations occurring during this period and the
      effective compressibility of the myocardium due to intramural fluid flow.
      Thereby, a realistic three-dimensional geometry derived from magnetic resonance
      imaging (MRI) measurements of both human ventricles was used. To validate our FE
      analyses, the results were compared with published measurements relating to the
      rapid filling phase of the human left ventricle. Our study shows that, under
      normal physiological conditions, ventricular aspiration plays a key role in the
      ventricular filling process.

PMID- 18068728
TI  - Mathematical modelling of cancer cell invasion of tissue: local and non-local
      models and the effect of adhesion.
AB  - The ability to invade tissue is one of the hallmarks of cancer. Cancer cells
      achieve this through the secretion of matrix degrading enzymes, cell
      proliferation, loss of cell-cell adhesion, enhanced cell-matrix adhesion and
      active migration. Invasion of tissue by the cancer cells is one of the key
      components in the metastatic cascade, whereby cancer cells spread to distant
      parts of the host and initiate the growth of secondary tumours (metastases). A
      better understanding of the complex processes involved in cancer invasion may
      ultimately lead to treatments being developed which can localise cancer and
      prevent metastasis. In this paper we formulate a novel continuum model of cancer
      cell invasion of tissue which explicitly incorporates the important biological
      processes of cell-cell and cell-matrix adhesion. This is achieved using non-local
      (integral) terms in a system of partial differential equations where the cells
      use a so-called "sensing radius"R to detect their environment. We show that in
      the limit as R-->0 the non-local model converges to a related system of reaction
      diffusion-taxis equations. A numerical exploration of this model using
      computational simulations shows that it can form the basis for future models
      incorporating more details of the invasion process.

PMID- 18068729
TI  - Big and tall parents do not have more sons.

PMID- 18068730
TI  - Identifying and characterising regulatory metabolites with generalised supply
      demand analysis.
AB  - We present the framework of generalised supply-demand analysis (SDA) of a kinetic
      model of a cellular system, which can be applied to networks of arbitrary
      complexity. By fixing the concentrations of each of the variable species in turn
      and varying them in a parameter scan, rate characteristics of supply-demand are
      constructed around each of these species. By inspecting the shapes of the rate
      characteristic patterns and comparing the flux-response coefficients of the
      supply and demand blocks with the elasticities of the enzymes that interact
      directly with the fixed metabolite, regulatory metabolites in the system can be
      identified and characterised. The analysis provides information on whether and
      where the system is functionally differentiated and which of its species are
      homeostatically buffered. The novelty in our proposed method lies in the fact
      that all metabolites are considered for SDA (hence the term "generalised"), which
      removes investigator bias. It supplies an entry point for the further analysis
      and detailed characterisation of large models of cellular systems, in which the
      choice of metabolite around which to perform a SDA is not always obvious.

PMID- 18068732
TI  - Neural rate equations for bursting dynamics derived from conductance-based
      equations.
AB  - A method of obtaining rate equations from conductance-based equations is
      developed and applied to fast-spiking and bursting neocortical neurons. It
      involves splitting systems of conductance-based equations into fast and slow
      subsystems, and averaging the effects of fast terms that drive the slowly varying
      quantities by showing that their average is closely proportional to the firing
      rate. The dependence of the firing rate on the injected current is then
      approximated in the analysis. The resulting behavior of the slow variables is
      then substituted back into the fast equations, with the further approximation of
      replacing the fast voltages in these terms by effective values. For bursting
      neurons the method yields two coupled limit-cycle oscillators: a self-exciting
      oscillator for the slow variables that commences limit-cycle oscillations at a
      critical current and modulates a fast spike-generating oscillator, thereby
      leading to slowly modulated bursts with a group of spikes in each burst. The
      dynamics of these coupled oscillators are then verified against those of the
      conductance-based equations. Finally, it is shown how to place the results in a
      form suitable for use in mean-field equations for neural population dynamics.

PMID- 18068731
TI  - Spatial invasion of cooperation.
AB  - The evolutionary puzzle of cooperation describes situations where cooperators
      provide a fitness benefit to other individuals at some cost to themselves. Under
      Darwinian selection, the evolution of cooperation is a conundrum, whereas non
      cooperation (or defection) is not. In the absence of supporting mechanisms,
      cooperators perform poorly and decrease in abundance. Evolutionary game theory
      provides a powerful mathematical framework to address the problem of cooperation
      using the prisoner's dilemma. One well-studied possibility to maintain
      cooperation is to consider structured populations, where each individual
      interacts only with a limited subset of the population. This enables cooperators
      to form clusters such that they are more likely to interact with other
      cooperators instead of being exploited by defectors. Here we present a detailed
      analysis of how a few cooperators invade and expand in a world of defectors. If
      the invasion succeeds, the expansion process takes place in two stages: first,
      cooperators and defectors quickly establish a local equilibrium and then they
      uniformly expand in space. The second stage provides good estimates for the
      global equilibrium frequencies of cooperators and defectors. Under hospitable
      conditions, cooperators typically form a single, ever growing cluster
      interspersed with specks of defectors, whereas under more hostile conditions,
      cooperators form isolated, compact clusters that minimize exploitation by
      defectors. We provide the first quantitative assessment of the way cooperators
      arrange in space during invasion and find that the macroscopic properties and the
      emerging spatial patterns reveal information about the characteristics of the
      underlying microscopic interactions.

PMID- 18068733
TI  - Impact of myxomatosis in relation to local persistence in wild rabbit
      populations: the role of waning immunity and the reproductive period.
AB  - Many diseases are less severe when they are contracted in early life. For highly
      lethal diseases, such as myxomatosis in rabbits, getting infected early in life
      can represent the best chance for an individual to survive the disease. For
      myxomatosis, early infections are attenuated by maternal antibodies. This may
      lead to the immunisation of the host, preventing the subsequent development of
      the lethal form of the disease. But early infection of young individuals requires
      specific demographic and epidemiological contexts, such as a high transmission
      rate of the pathogen agent. To investigate other factors involved in the impact
      of such diseases, we have built a stochastic model of a rabbit metapopulation
      infected by myxomatosis. We show that the impact of the pathogen agent can be
      reduced by early infections only when the agent has a long local persistence time
      and/or when the host subpopulations are highly connected. The length of the
      reproductive period and the duration of acquired immunity are also important
      factors influencing the persistence of the pathogen and thus, the impact of the
      disease. Besides confirming the role of classical factors in the persistence of a
      pathogen agent, such as the size of the subpopulation or the degree of
      connectivity, our results highlight novel factors that can modulate the impact of
      diseases whose severity increase with age.

PMID- 18068734
TI  - Contamination profiles of heavy metals, organochlorine pesticides, polycyclic
      aromatic hydrocarbons and alkylphenols in sediment and oyster collected from
      marsh/estuarine Savannah GA, USA.

PMID- 18068736
TI  - Repetition of distractor sets improves visual search performance in hemispatial
      neglect.
AB  - Priming from repeated distractor sets, or search context, in conjunctive visual
      search was examined in four patients with hemispatial neglect. In the first
      experiment overall context was either changed or repeated while the target was
      always the same to control for any modulatory effect of target priming.
      Considerable priming was seen from repeated context. In the second experiment the
      context was either repeated on the left side, on the right side, on both sides,
      or the context was new. Priming from repeated context was found to arise from the
      left visual field, as well as the right visual field, as well as when overall
      context was repeated. Brief masked displays were used in experiment 3, the
      results again showing strong priming from repeated overall context. The results
      of the three experiments suggest that visual grouping, or perceptual
      organization, of distractor sets is relatively intact in the affected hemifield
      of parietal neglect patients. Furthermore, repetition of context may even
      temporarily ameliorate neglect symptoms in search. These findings are consistent
      with claims that grouping is distinct from attentional processing and that it
      operates at lower levels of the perceptual hierarchy.

PMID- 18068735
TI  - Heterogeneity of barrier function in the lung reflects diversity in endothelial
      cell junctions.
AB  - Endothelial cells assemble unique barriers that confer specific permeability
      requirements at different vascular segments. We examined lung microvascular and
      artery endothelial cells to gain insight into mechanisms for segment-specific
      barrier functions. Transendothelial electrical resistance was significantly
      higher in microvascular barriers, and a 50% reduction in barrier function
      required 5-fold higher concentration of cytochalasin D in the microvascular
      compared to the arterial barrier. Transcriptional profiling studies identified N
      cadherin and activated leukocyte cell adhesion molecule (ALCAM) to be most highly
      expressed in microvascular than in pulmonary artery endothelial cells. ALCAM was
      detected in microvascular endothelial cells in the alveolar septum but not in
      endothelial cells in larger pulmonary vessels in situ. This pattern was retained
      in culture as ALCAM was recruited to cell junctions in pulmonary microvascular
      endothelial cells but remained predominantly cytosolic in pulmonary artery
      endothelial cells. Confocal analysis revealed ALCAM in the lateral plasma
      membrane domain where it co-localized with N- and VE-cadherin. This finding was
      supported by co-immunoprecipitation studies demonstrating the presence of ALCAM
      in multiple adherens junction protein complexes. These functional, biophysical
      and molecular findings suggest specialization of the adherens junction as a basis
      for a highly restrictive endothelial barrier to control fluid flux into the
      alveolar airspace.

PMID- 18068737
TI  - Simultaneous recording of EEG and facial muscle reactions during spontaneous
      emotional mimicry.
AB  - The perception of emotional facial expressions induces covert imitation in
      emotion-specific muscles of the perceiver's face. Neural processes involved in
      these spontaneous facial reactions remain largely unknown. Here we concurrently
      recorded EEG and facial EMG in 15 participants watching short movie clips
      displaying either happy or angry facial expressions. EMG activity was recorded
      for the zygomaticus major (ZM) that elevates the lips during a smile, and the
      corrugator supercillii (CS) that knits the eyebrows during a frown. We found
      increased EMG activity of CS in response to angry expressions, and enhanced EMG
      activity of ZM for happy expressions, replicating earlier EMG studies. More
      importantly, we found that the amplitude of an early visual evoked potential
      (right P1) was larger when ZM activity to happy faces was high, and when CS
      activity to angry faces was high, as compared to when muscle reactions were low.
      Conversely, the amplitude of right N170 component was smaller when the intensity
      of facial imitation was high. These combined EEG-EMG results suggest that early
      visual processing of face expression may determine the magnitude of subsequent
      facial imitation, with dissociable effects for P1 and N170. These findings are
      discussed against the classical dual-route model of face recognition.

PMID- 18068738
TI  - Multivariate analysis of the modifications induced by an environmental acoustic
      cue on rat exploratory behavior.
AB  - The aim of the present paper is to study by means of a multivariate analysis the
      modifications induced by an environmental acoustic cue on the structure of rat
      exploratory behavior. Adult male Wistar rats were observed during the exploration
      of a soundproof observation box. Each rat was acoustically stimulated after 150 s
      from the beginning of the experimental session, lasting 300 s, and recorded
      through a digital videocamera. A frame by frame analysis was thereafter carried
      out using a professional video-recording system. Thirteen behavioral patterns
      were selected: immobility, immobile-sniffing, walking, rearing, climbing,
      chewing, paw-licking, face-grooming, body-grooming, head-turning, tuning,
      oriented-sniffing, focusing. Both descriptive and multivariate analyses (cluster,
      stochastic, adjusted residuals) were carried out. Through descriptive statistical
      analysis, latencies and per cent distribution of each pattern were studied. A
      multivariate cluster analysis revealed the presence of three main behavioral
      clusters, an additional one being identified following acoustic stimulation.
      Multivariate stochastic analysis showed that all the patterns converged on
      immobile-sniffing which could represent a key component in behavioral switching
      processes related to environmental exploration. Moreover, through adjusted
      residuals, the degree of relationship among different patterns was shown
      according to statistic Z-distribution. Our data assign new ethological meanings
      to different behavioral patterns. Notably, head-turning is suggested to be
      considered as a generic directional search and tuning as a subtle activity of
      stimulus localization.

PMID- 18068739
TI  - Selective blockade of the rat brain aqueduct with thermogelling hydrogel
      nanoparticle dispersion.
AB  - Experimental methods targeting molecules or drugs to specific neuronal tissue(s)
      can be important in determining function. In this study we focused on blockade of
      the small channel or aqueduct connecting the third and fourth ventricles of the
      rat brain. A cannula was placed into the aqueduct between the third and fourth
      ventricle. A second cannula was placed into the third or fourth ventricle. An
      aqueous dispersion of hydrogel nanoparticles, that maintains a liquid state at
      temperatures below 33 degrees C and solidifies near body temperature (35 degrees
      C), was infused into the aqueduct. Two interpenetrating polymer networks (IPN) of
      hydrogel nanoparticles with polymer concentrations at 2% by weight and 3% by
      weight were separately infused into the aqueduct to block cerebrospinal fluid
      (CSF) flow. Following infusion of hydrogel CSF was isolated to a particular
      ventricle as shown by the lack of dye movement between the ventricles. In
      addition, stress hormone, corticosterone, feeding behavior and blood glucose
      levels were measured. Results show upon reaching the aqueduct the hydrogel
      dispersion solidified and restricted the flow of CSF. A higher concentration of
      dispersion (3% wt.) was more effective in blocking the aqueduct and isolating the
      third from the fourth ventricle. Over the period of measurement, infusion of the
      dispersion had no measurable detrimental physiological effects on the animal. We
      conclude that isolation of ventricles in the brain can be completed for 48-h by
      using dispersions of hydrogel nanoparticles and the effects of drugs on certain
      brain tissues can be determined with this method.

PMID- 18068740
TI  - The inflammatory response to social defeat is increased in older mice.
AB  - KINSEY, S. G., BAILEY, M. T., SHERIDAN, J. F., PADGETT, D. A. The inflammatory
      response to social defeat is increased in older mice. PHYSIOL BEHAV 91(0) 000
      000, 2007. Previous research indicates that repeated social defeat of mice causes
      increased lymphocyte trafficking to the spleen, elevated proinflammatory cytokine
      production, and induced glucocorticoid insensitivity in splenocytes. Social
      defeat also causes increases in anxiety-like behavior. This study investigated
      whether repeated social defeat results in similar immunoregulatory and behavioral
      changes in older mice as those seen previously in young adult mice. The data
      revealed that, regardless of age, defeated mice had significantly more splenic
      CD11b+ Gr-1+ monocytes and neutrophils than controls. Supernatants harvested from
      cultured splenocytes from older mice contained comparatively higher IL-6 and TNF
      alpha than supernatants from younger animals. In addition, those same cells
      derived from older defeated mice were hypersensitive to lipopolysaccharide (LPS)
      and insensitive to glucocorticoids in vitro. As seen previously in young adult
      mice, social defeat caused an increase in anxiety-like behavior in the open field
      test, but had no effect on learned helplessness in the forced swim test. These
      data indicated that repeated social defeat results in a proinflammatory state
      that is exacerbated in older mice. The implications of these data are noteworthy,
      given the strong role of inflammation in many age-related diseases.

PMID- 18068741
TI  - Transient occurrence of an ebulin-related D-galactose-lectin in shoots of
      Sambucus ebulus L.
AB  - Young shoots of Sambucus ebulus L. contain a monomeric d-galactose binding lectin
      (SELlm), which disappears upon shoot development, and was previously undetected
      since it co-purifies with the non-toxic type 2 ribosome-inactivating protein
      ebulin l and the dimeric lectin SELld. Molecular cloning of cDNA coding for SELlm
      and mass spectrometry analysis revealed a protein with a molecular mass of 34,239
      Da, which displays 80%, 77% and 45% of amino acid sequence identity with the
      ebulin l-B chain, SELld and ricin-B chain, respectively. Furthermore, the cloned
      precursor, with respect to the ebulin l precursor is truncated and contains the
      signal peptide, a piece of the A chain, a piece of the connecting peptide and the
      B chain. Further processing yields the lectin protein, which contains only the B
      chain. Despite the fact that SELlm displays the same d-galactose-binding sites
      than ricin, it was found that the lectin has different binding properties to D
      galactose-containing matrix than ricin. Notably, and unlike ricin, the binding of
      SELlm and other Sambucus lectins to such matrix was maximum in range of 0-10
      degrees C and abolished at 20 degrees C.

PMID- 18068742
TI  - Testosterone profiles and their correlation with sexual libido in male camels.
AB  - The study was conducted on 4 male Jaisalmeri camels (Camelus dromedarius) on
      their circulating testosterone (T) profiles and correlation with sexual libido.
      The average T concentration was low during hot months of April to September,
      started increasing in the months of October and November, continued to increase
      steadily in the months of December, January and February followed by decline in
      the ensuing months. Individual variations in onset and cessation of T surge were
      observed. Sexual libido as indicated by copulation time (CT) and volume of semen
      ejaculated (V) was high during January to April months, declined slowly over May
      month followed by complete cessation in later half of June. Sexual libido was
      almost negligible during July to November months. The sexual libido was also low
      during December month. Like circulating T profiles, individual variations were
      also observed in sexual libido. Data indicated that onset as well as cessation of
      T surge preceded the onset and cessation of sexual libido in all the animals. A
      positive correlation was found among circulating T (concentration), CT and V of
      semen. It is concluded that seasonal changes in circulating testosterone governs
      sexual libido in male camels.

PMID- 18068744
TI  - Oxysterols: novel biologic roles for the 21st century.
AB  - A major focus for the 21st century are the sterol intermediates in cholesterol
      synthesis and their metabolites. No longer considered inactive way stations in
      their transformation to cholesterol, both physiologic and pathophysiologic
      studies, though early in their development, indicate novel biologic roles for
      these sterols, and their oxysterol metabolites that bypass cholesterol, the
      expected end product. A major impetus for further inquiry is the recognition that
      in genetically determined errors in cholesterol synthesis such as Smith-Lemil
      Opitz syndrome, the phenotypic effects on the developing fetus are not solely
      attributable to the lack of cholesterol but the accumulation of 7
      dehydrocholesterol and its 27-hydroxy metabolite. This view is now supported by a
      new mouse model, the double knockout Insig1 & 2 (insulin-induced genes 1 & 2) in
      which lack of the protein product results in a greater production of lanosterol
      compared to cholesterol during fetal life with severe dysmorphic consequences.
      Further support can be derived from in vitro studies of the Sonic hedgehog
      signaling pathway, essential for normal morphogenesis in the central nervous
      system and perhaps other organs, which may require the local presence of
      oxysterols for full expression. Future studies that can delineate the specific
      role of a sterol intermediate or its metabolite require a paradigm shift away
      from the generic use of oxysterols as a class of compounds to a focus on specific
      sterols that can be expected in tissues and techniques for mimicking the local
      environment. Another class of oxysterols are those arising by photoxidation, now
      considered to be an expected event generated by the photons of visible blue light
      and therefore pari passu with normal vision. The sequence of events from
      peroxides of cholesterol to hydroxy and keto derivatives is the signature of
      singlet oxygen as opposed to free radicals and other mechanisms for generating
      reactive oxygen species. Perhaps surprisingly, the retina expresses CYP 27A1 and
      CYP 46A1, enzymes with broad substrate specificity for ring-modified sterols,
      implying that, in addition to a rich blood supply for disposing of potentially
      toxic oxysterols, they can be detoxified locally. Recognition that the retina has
      nuclear receptors similar to those found in other tissues raises the possibility
      that the sterols that are generated may function in their traditional role as
      ligands for modulating gene expression but other, nonligand, activities can be
      expected since other proteins such as the oxysterol-binding proteins exist and
      are considered to have biologic activities. To critically evaluate these
      potentially new biologic roles for oxysterols a need exists for the synthesis and
      utilization of the expected naturally occurring metabolites rather than available
      surrogates that may not be truly representative of their tissue effects and to
      utilize analytical techniques that can identify their existence at the expected
      concentrations in tissues.

PMID- 18068743
TI  - Differential effects of estrogen and progesterone on potassium channels expressed
      in Xenopus oocytes.
AB  - HYPOTHESIS: Potassium (K(+)) channel activation contributes in part to estrogen
      mediated vasorelaxation. However, the underlying mechanism is still unclear. We
      hypothesize that estrogen increases K(+) currents via membrane-associated, non
      genomic interaction and that steroid hormones have differential effects on
      different types of K(+) channels. EXPERIMENTAL: Human large-conductance Ca(2+)
      activated K(+) channels (BK(Ca)) and human voltage-gated K(+) channels (K(V1.5))
      were expressed in Xenopus oocytes, and K(+) currents elicited by voltage clamp
      were measured. RESULTS: Both 17beta-estradiol and BSA-conjugated 17beta-estradiol
      increased the BK(Ca) current in a concentration-dependent manner and this effect
      was abolished by tetraethylammonium ions and iberiotoxin (putative BK(Ca) channel
      blockers). 17beta-estradiol-stimulated increase in the BK(Ca) current was
      unaffected by treatment with ICI 182,780 (classic estrogen receptor antagonist),
      tamoxifen (estrogen receptor agonist/antagonist), actinomycin D (RNA synthesis
      inhibitor), or cycloheximide (protein synthesis inhibitor). In contrast,
      progesterone reduced the BK(Ca) current in the absence or presence of NS 1619
      (BK(Ca) channel activator). Progesterone also inhibited 17beta-estradiol
      stimulated increase in the BK(Ca) current. Finally, progesterone but not 17beta
      estradiol reduced the K(V1.5) current. CONCLUSIONS: The present results show that
      17beta-estradiol stimulates BK(Ca) channels without affecting K(V1.5) channels.
      This effect is ICI 182,780-insensitive and is likely mediated via a membrane
      bound binding site. Progesterone inhibits both BK(Ca)- and K(V1.5)-encoded
      currents. The present results suggest that inhibition of K(+) channels may
      contribute in part to its reported antagonism against 17beta-estradiol-mediated
      vascular relaxation via BK(Ca) channels.

PMID- 18068746
TI  - Primary culture of venom glands from the Brazilian armed spider, Phoneutria
      nigriventer (Araneae, Ctenidae).
AB  - Phoneutria spider venoms are a rich source of bioactive components. The limited
      amounts of crude material available, however, can be considered as a major
      hindrance for a faster development in the field. In the present study, we
      attempted to establish primary cultures of venom glands of Phoneutria nigriventer
      as an alternative, in vitro source of venom. Three different developmental stages
      were tried as starting materials: whole embryo (inside the cocoon), nymph (early
      after cocoon hatching) and young adult (1 year after cocoon hatching). The
      embryonic cells remained in suspension in the primary cultures, with no signs of
      adhesion or differentiation, for about 6 months. Nevertheless, this culture was
      useful for the first chromosome C-banding of Phoneutria. An average of 29+/-1
      acrocentric chromosomes were found. Striated muscle cells were the only kind of
      cells in the culture of venom glands from Phoneutria nymphs. The most promising
      results were achieved with 1-year-old specimens. Besides muscle, adherent
      epithelial cells were also obtained in culture. Although these cells remained in
      culture for a short time (up to 48 h) immunochemical analysis of the culture
      supernatant evidenced the presence of Phoneutria venom components. This can be
      considered as a first step toward the functional cultures of venom glands of
      Phoneutria spiders.

PMID- 18068745
TI  - Mechanistic investigations on the antioxidant action of a neuroprotective
      estrogen derivative.
AB  - Antioxidant action is an important component of the complex neuroprotective
      effect of estrogens. Combining theoretical prediction and subsequent experimental
      confirmation by chemical and in vitro paradigms, this study focused on the
      mechanistic aspects of hydroxyl radical scavenging by 17beta-butoxy-1,3,5(10)
      estratrien-3-ol, a synthetic derivative of 17beta-estradiol with increased
      potency to inhibit lipid peroxidation and reduced affinity to estrogen-receptors
      compared to the endogenous hormone. In the process that acts as a "chemical
      shield," the phenolic A-ring turns into 10beta-hydroxy-17beta-butoxy-1,3,5(10)
      estratrien-3-one, a non-aromatic para-quinol, upon capturing hydroxyl radicals,
      which results in the complete loss of estrogen-receptor affinity and antioxidant
      activity. However, the parent compound is apparently recovered in brain tissue
      from this para-quinol via enzyme-catalyzed NAD(P)H-dependent reductive
      aromatization without causing oxidative stress. Taken together, our report argues
      for a previously unrecognized antioxidant cycle for estrogen-derived compounds.

PMID- 18068747
TI  - Study of cell killing effect on S180 by ultrasound activating protoporphyrin IX.
AB  - The present study was initiated to investigate the potential biological mechanism
      of cell killing effect on isolate sarcoma 180 (S180) cells induced by ultrasound
      activating protoporphyrin IX (PPIX). S180 cells were exposed to ultrasound for
      30s duration, at a frequency of 2.2 MHz and an acoustic power of 3 W/cm(2) in the
      presence of 120 microM PPIX. The viability of cells was evaluated using trypan
      blue staining. The generation of oxygen free radicals in cell suspensions was
      detected immediately after treatment using a reactive oxygen detection kit. A
      copper reagent colorimetry method was used to measure the level of FFAs released
      into cell suspensions by the process of cell damage induced by ultrasound and
      PPIX treatment. Oxidative stress was assessed by measuring the activities of key
      antioxidant enzymes (i.e., SOD, CAT, GSH-PX) in S180 tumor cells. Treatment with
      ultrasound and PPIX together increased the cell damage rate to 50.91%, while
      treatment with ultrasound alone gave a cell damage rate to 24.24%, and PPIX alone
      kept this rate unchanged. Colorimetry and enzymatic chemical methods showed that
      the level of FFAs in cell suspension increased significantly after the treatment,
      while the activity of all the above enzymes decreased in tumor cells at different
      levels, and were associated with the generation of oxygen free radicals in cell
      suspension after treatment. The results indicate that oxygen free radicals may
      play an important role in improving the membrane lipid peroxidation, degrading
      membrane phospholipids to release FFAs, and decreasing the activities of the key
      antioxidant enzymes in cells. This biological mechanism might be involved in
      mediating the effects on S180 cells and resulting in the cell damage seen with
      SDT.

PMID- 18068748
TI  - Efficient inhibition of SIV replication in rhesus CD4+ T-cell clones by
      autologous immortalized SIV-specific CD8+ T-cell clones.
AB  - CD8(+) cytotoxic T lymphocyte (CTL) responses play an important role in
      controlling the replication of primate lentiviruses. Induction of these responses
      is a key objective for most current AIDS vaccine approaches. Despite a variety of
      approaches for measuring properties and activities of CTL, the functions
      responsible for controlling viral replication in vivo have not been clearly
      identified. Assays measuring CTL-mediated suppression of viral replication in
      vitro are beginning to be used as possible correlates of in vivo virus
      suppressive activity, but the utility and interpretive value of these assays are
      typically limited by properties of the cells that have been used. We investigated
      the capacity of SIV-specific CTL clones (effectors), immortalized by transduction
      with human telomerase reverse transcriptase (hTERT), to suppress SIV replication
      in autologous hTERT immortalized CD4(+) T-cell clones (targets). Immortalized and
      non-immortalized SIV-specific effector cells showed IFN-gamma production and
      degranulation in response to viral antigen specific stimulation and significantly
      inhibited SIV(mac)239 replication (2 to 4 log decrease in viral RNA or cell
      associated proviral DNA) (p<0.0005). Our in vitro assays of inhibition of viral
      replication, using T-cell clones as effectors and targets, provide a well-defined
      approach for evaluating possible mechanisms of CTL-mediated control of viral
      production which may involve direct killing of infected target cells and/or
      release of proinflammatory cytokines such as IFN-gamma and TNF-alpha. The use of
      hTERT immortalized effector and target cells for such assays preserves relevant
      functional properties while providing a convenient, reproducible means of
      conducting studies over time.

PMID- 18068749
TI  - Protein coding content of the UL)b' region of wild-type rhesus cytomegalovirus.
AB  - A recent comparison of two rhesus cytomegalovirus (RhCMV) genomes revealed that
      the region at the right end of the U(L) genome component (U(L)b') undergoes
      genetic alterations similar to those observed in serially passaged human
      cytomegalovirus (HCMV). To determine the coding content of authentic wild-type
      RhCMV in this region, the U(L)b' sequence was amplified from virus obtained from
      naturally infected rhesus macaques without passage in vitro. A total of 24 open
      reading frames (ORFs) potentially encoding >99 amino acid residues were
      identified, 10 of which are related to HCMV ORFs and 15 to previously listed
      RhCMV ORFs. In addition, the analysis revealed a cluster of three novel alpha
      chemokine-like ORFs, bringing the number of predicted alpha chemokine genes in
      this region to six. Three of these six genes exhibit a high level of sequence
      diversity, as has been observed for the HCMV alpha chemokine gene UL146.

PMID- 18068751
TI  - Interaction between complex motion patterns in the perception of shape.
AB  - We investigated how different types of complex motion patterns interact in the
      perception of shape. We used global dot-motion stimuli which consisted of two
      superimposed groups of dots; one group of dots moved along an ellipsoidal
      trajectory (target pattern), while the other group of dots was divided into
      quadrants with dots in alternating sectors moving in radial expanding and radial
      contracting directions (background pattern). In the first experiment, observers
      judged whether the major axis of an ellipsoidal motion pattern oriented at 45
      degrees or -45 degrees from vertical lay to the right or to the left of a central
      vertical line. Ellipsoids with different aspect ratios, which controlled both the
      tilt (left or right of vertical) and the extent of ellipsoidal curvature, were
      presented to observers using method of constant stimuli. The appearance of the
      ellipsoidal target pattern was distorted in the presence of background motion.
      The aspect ratio of the target at which observers perceived the figure to be
      circular was approximately 0.86 (an aspect ratio of 1.0 indicates a circle), with
      the pattern's major axis lying in the two sectors that contained contracting
      motion. This finding may constitute evidence that background motion distorts the
      perception of space, resulting in a distorted target pattern. However, the
      distortion effect is limited to conditions for which the speed of the target
      pattern and background pattern was slow and high contrast, and for when dots
      forming the target and background patterns were of the same luminance polarity.

PMID- 18068750
TI  - Assessment of antibody responses against gp41 in HIV-1-infected patients using
      soluble gp41 fusion proteins and peptides derived from M group consensus
      envelope.
AB  - Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 is
      targeted by broadly-reactive neutralizing antibodies 2F5 and 4E10, making it an
      attractive target for vaccine development. To better assess immunogenic
      properties of gp41, we generated five soluble glutathione S-transferase fusion
      proteins encompassing C-terminal 30, 64, 100, 142, or 172 (full-length) amino
      acids of gp41 ectodomain from M group consensus envelope sequence. Antibody
      responses in HIV-1-infected patients were evaluated using these proteins and
      overlapping peptides. We found (i) antibody responses against different regions
      of gp41 varied tremendously among individual patients, (ii) patients with
      stronger antibody responses against membrane-proximal external region exhibit
      broader and more potent neutralizing activity, and (iii) several patients mounted
      antibodies against epitopes that are near, or overlap with, those targeted by 2F5
      or 4E10. These soluble gp41 fusion proteins could be an important source of
      antigens for future vaccine development efforts.

PMID- 18068752
TI  - Spatial cueing deficits in dyslexia reflect generalised difficulties with
      attentional selection.
AB  - Traditionally, explanations of spatial cueing effects posit the operation of
      orienting mechanisms that act to reposition the spatial locus of attention. This
      process is often viewed to be analogous to the movement of an attentional
      'spotlight' across the visual field to the cued region and is thought to occur
      either in an exogenous or endogenous manner, depending on the nature of the cue.
      In line with this view, anomalous findings in dyslexic groups using paradigms
      involving brief peripheral cues have been interpreted as evidence for a
      particular deficiency with stimulus-driven, exogenous orienting. Here, we
      demonstrate that an exogenous orienting deficit is an unfeasible explanation of
      recent findings in which dyslexic individuals fail to derive benefit from
      peripheral cues indicating the location of a target in a single fixation visual
      search task. In a series of experiments examining cueing effects in normal
      readers, we find no evidence to support the operation of an attentional orienting
      mechanism that is (i) fast but transient; (ii) automatic and involuntary; and
      (iii) preferentially driven by abrupt luminance transients. Rather, we find that
      the magnitude of obtained benefits is primarily determined by the informational
      value of the cue (irrespective of how information is conveyed) and the
      accessibility of the target representation once the cue had been delivered. In
      addition, we show that dyslexic individuals' difficulties with cued search do not
      reflect problems with detecting and localising the cue, and generalize to
      different cue types. These results are consistent with a general weakness of
      attentional selection in dyslexia.

PMID- 18068753
TI  - Dechlorination of trichloroethylene formed from 1,1,2,2-tetrachloroethane by
      dehydrochlorination in Portland cement slurry including Fe(II).
AB  - Transformation of 1,1,2,2-tetrachloroethane (1,1,2,2-TeCA) by Fe(II) in 10%
      cement slurries was characterized using a batch reactor system. 1,1,2,2-TeCA was
      completely converted to trichloroethylene (TCE) within 1h in all experiments,
      even in controls with cement that did not include Fe(II). Therefore, complete
      degradation of 1,1,2,2-TeCA depends on the behavior of TCE. The half-life of TCE
      was observed to be 15d when concentrations of Fe(II) and 1,1,2,2-TeCA were 98mM
      and 0.245mM, respectively. The kinetics of TCE removal was observed to be
      dependent on Fe(II) dose, pH and initial substrate concentration. Pseudo-first
      order rate constants linearly increased with Fe(II) dose up to 198mM when initial
      target concentration was 0.245mM. Pseudo-first-order kinetics generally described
      the degradation reactions of TCE at a specific initial concentration, but a
      modified Langmuir-Hinshelwood model was necessary to describe the degradation
      kinetics of TCE over a wide range of initial concentrations. A surface reaction
      of TCE on active solids, which were formed from Fe(II) and products of cement
      hydration appears to control observed TCE degradation kinetics.

PMID- 18068754
TI  - Effect of ortho-chlorine substitution on the partition behavior of chlorophenols.
AB  - Chlorophenol isomers are known to possess substantially different octanol/water
      and octane/water partition constants depending on whether the chlorine
      substituents are in the ortho or meta/para position. Here we show that the same
      is also true for environmental partition processes such as water/air and humic
      acid/air partitioning. Quantitative structure property relationships (QSPR) such
      as those in the widely used EPI-suite or SPARC fail to correctly predict this
      influence of the substituent position on the compound's partitioning. Only a more
      sophisticated quantum chemical software, called COSMOtherm, correctly reproduced
      these effects. Based on this and earlier experiences we conclude that COSMOtherm
      may be a better tool for screening large sets of chemicals for which no
      experimental data on their partitioning yet exist.

PMID- 18068755
TI  - Identification of p53-dependent genes potentially involved in UVB-mediated
      premature senescence of human skin fibroblasts using siRNA technology.
AB  - Premature senescence of skin human diploid fibroblasts is induced after a series
      of 10 sublethal exposures to UVB at 2.5 kJ/m(2) with appearance of several
      biomarkers of cellular senescence like senescence-associated beta-galactosidase
      activity (SA beta-gal) and cell cycle arrest. Herein it is shown that the
      induction of UVB-induced premature senescence is associated with a transient
      increase of protein abundance and DNA-binding activity of p53. Silencing p53
      expression with small interfering RNA (siRNA) affected the basal level of SA beta
      gal and proliferative potential, but did not prevent UVB-induced increase of SA
      beta-gal and decrease of DNA synthesis. We used a senescence-specific low-density
      DNA array and p53 siRNA to study the mRNA abundance of 240 senescence-related
      genes and identified several potential p53-dependent genes differentially
      expressed after the repeated exposures to UVB.

PMID- 18068756
TI  - Antiphospholipid syndrome after non-myeloablative hematopoietic cell
      transplantation.

PMID- 18068757
TI  - Seasonal emission of seminal coagulum and in vivo sperm dynamics in the black
      handed spider monkey (Ateles geoffroyi).
AB  - The ejaculate of diverse primate species consists of two portions, liquid and
      solid; the latter, known as the seminal coagulum, is thought to sequester large
      numbers of sperm. In the black-handed spider monkey (Ateles geoffroyi),
      ejaculates collected by electroejaculation did not always contain seminal
      coagulum. The objective of the present study was to determine seasonal emission
      of seminal coagulum and in vivo sperm dynamics in the black-handed spider monkey.
      Seminal coagulum emission was related to season; it was more frequent in the dry
      season, coincident with maximal female fertility. Sperm concentration was higher
      (P = 0.02) in the dry season (dry vs. rainy season: 137.9 +/- 15.7 sperm/mL vs.
      82.56 +/- 14.7 x1 0(6) sperm/mL; mean +/- S.E.M.) but also in ejaculates
      (collected during the rainy season) that had seminal coagulum (coagulum vs. no
      coagulum: 140.0 +/- 29.3 sperm/mL vs. 31.2+/-0.1 x 10(6) sperm/mL, P<0.001). In
      semen samples collected from the uterus after AI, the percentage of linearly
      motile sperm was higher during the dry season (dry vs. rainy: 9.1+/-2.1% vs.
      5.9+/-2.5%), as well as whenever coagulum was present (coagulum vs. no coagulum:
      13.0+/-3.2% vs. 2.0+/-0.9%, P<0.001).

PMID- 18068758
TI  - Progressive agraphia can be a harbinger of degenerative dementia.
AB  - By investigating three patients with progressive agraphia, we explored the
      possibility that this entity is an early sign of degenerative dementia.
      Initially, these patients complained primarily of difficulties writing Kanji
      (Japanese morphograms) while other language and cognitive impairments were
      relatively milder. Impairments in writing Kana (Japanese syllabograms), verbal
      language, executive function, visuo- and visuospatial cognition and memory were
      identified by neuropsychological testing. The agraphia was compatible with a
      peripheral type, based on deficits at the interface between the central letter
      selection and the graphemic motor execution (Patient 1) or at the stage of
      central letter selection as well (Patients 2 and 3). Agraphia was generally more
      prominent, although not exclusive, for Kanji probably because of later
      acquisition and larger total number of Kanji letters leading to lower frequency
      of use and familiarity per letter. Concurrent or subsequent emergence of non
      fluent aphasia, ideomotor apraxia, executive dysfunction and asymmetric akinetic
      rigid syndrome in two patients suggested degenerative processes involving the
      parietal-occipital-temporal regions, basal ganglia and striato-frontal
      projections. We propose that progressive agraphia may be one of the early
      symptoms of degenerative dementia such as corticobasal degeneration.

PMID- 18068759
TI  - Personalized therapy in chronic viral hepatitis.
AB  - Chronic carriers of major hepatitis viruses (i.e., hepatitis B and C viruses, HBV
      and HCV) account for at least 600 millions people worldwide. About 50% of them
      are at risk for chronic hepatitis and 20-30% of patients with chronic hepatitis
      develop progressive liver disease and symptomatic life-threatening liver lesions.
      Therefore, the identification of the carrier at risk is mandatory to prevent
      progressive liver disease, avoiding non-appropriate treatments. The decision
      making has three major steps. The 1st is the identification of the patient who
      needs to be treated; the 2nd is the choice of the best therapeutic strategy and
      the most appropriate drugs and timing during the phase of infection and disease;
      the 3rd is the treatment optimization to reduce non effective therapy and avoid
      drug resistance virus mutants. This careful evaluation takes into account the
      individual variability, the host/virus interplays and the drug impact on viral
      replication with the risk of selection of resistant mutants. The complexity of
      the virus/host interactions, however, cannot be managed by simple mean of
      probabilistic statistics and/or step-wise algorithms based on population
      statistics. A better answer for personalized antiviral therapy may come from the
      combined use of molecular biology and bio-mathematical modeling that can help the
      medical doctor to follow the dynamic of viral infection during therapy, like the
      flight simulator helps the pilot. We provide a concise review of the potentials
      of this approach in clinical practice.

PMID- 18068760
TI  - Comparative study of performances of lipase immobilized asymmetric polysulfone
      and polyether sulfone membranes in olive oil hydrolysis.
AB  - In the present study, lipase was immobilized via glutaraldehyde crosslinking on
      the polysulfone and polyether sulfone asymmetric membranes. The results indicated
      that the overall immobilization of lipase is related to the hydrophobicity of the
      membrane material and thus higher immobilization is achieved for polysulfone
      membrane. The evidence of immobilization is done by XRD, SEM, contact angle and
      porometric studies. Hydrolytic activity of lipase in immobilized form is
      determined by hydrolyzing olive oil and compared with hydrolytic activity of free
      lipase. The effect of different reaction parameters viz., temperature, pH,
      substrate concentration, and incubation time on the lipase activity is
      investigated. The observed maximum reaction rate (V(max)) and Michaelis-Menten
      constant (K(m)) of polysulfone and polyether sulfone is determined.

PMID- 18068761
TI  - Case report: twin-to-twin transfusion syndrome resulting from placental
      collateral artery development.
AB  - BACKGROUND: The twin-to-twin transfusion syndrome (TTTS) is a severe complication
      of monochorionic twin pregnancies, caused by a net inter-twin transfusion of
      blood from one fetus (the donor) towards the other fetus (the recipient) through
      placental anastomoses. TTTS is driven by unidirectional arterio-venous
      anastomoses, and mitigated by bidirectional arterio-arterial or veno-venous
      anastomoses which reduce the net inter-twin transfusion. In contrast to these
      accepted concepts, cases have been described paradoxically devoid of arterio
      venous anastomoses but including arterio-arterial anastomoses. We hypothesized
      that TTTS may develop in such cases as a consequence of a stenosed chorionic
      artery in the recipient placenta that connects with the arterio-arterial
      anastomosis. CLINICAL CASES: We describe two cases of monochorionic twin
      placentae without arterio-venous anastomoses but with only an arterio-arterial
      and veno-venous anastomosis. In one case severe TTTS developed. There, the
      arterio-arterial anastomosis connected to a stenosed chorionic artery in the
      recipient placenta and showed a tortuous appearance. The other case developed
      uneventful. It lacked a stenosed chorionic artery and the arterio-arterial
      anastomosis was non-tortuous. CONCLUSION: We present evidence that the arterio
      arterial anastomosis represented a functional collateral artery whose outgrowth
      was driven by an increased shear-stress caused by an increased flow to a lower
      pressure vascular bed in the placenta of the recipient. The lower arterial
      pressure occurred from the moment that a chorionic artery which was connected to
      the anastomosis developed a significant stenosis. The resulting collateral flow
      through the anastomosis maintained blood supply to the lower pressure placental
      bed, the beneficial function of collaterals, but also resulted in an increasing
      net inter-twin transfusion which triggered onset of severe TTTS.

PMID- 18068762
TI  - Synthesis and pharmacological characterization of a novel, highly potent,
      peptidomimetic delta-opioid radioantagonist, [3H]Tyr-Tic-(2S,3R)-beta-MePhe-Phe
      OH.
AB  - [(3)H]Tyr-Tic-(2S,3R)-beta-MePhe-Phe-OH (where Tic: 1,2,3,4
      tetrahydroisoquinoline-3-carboxylic acid) with a specific radioactivity of 53.7
      Ci/mmol was synthesized and characterized in receptor binding assays at 25
      degrees C in rat brain membranes. The specific binding was saturable and
      displayed high affinity, with a K(D) of 0.16+/-0.005 nM and B(max) of 85.9+/-6.3
      fmol/mg protein. NaCl increased its affinity by about 4-fold in membranes of rat
      brain and Chinese Hamster Ovary Cells stably transfected with the human delta
      opioid receptors (hDOR-CHO) showing that the new ligand is an antagonist. The
      prototypic delta-opioid ligands were much more potent than mu- or kappa-specific
      ligands in competition assays. The autoradiographic distribution of the binding
      sites of the new ligand agreed with the known locations of the delta-opioid
      receptors in rat brain. The unlabeled new ligand was about 7-fold more potent
      than the parent peptide in competing for the binding sites of [(3)H]Tyr-Tic
      (2S,3R)-beta-MePhe-Phe-OH in rat brain membranes. Likewise, the threo-beta-methyl
      analog was 3.8-fold more potent than the parent compound in antagonizing the
      effect of DPDPE in the [(35)S]GTPgammaS functional assay in hDOR-CHO membranes.
      The new, highly potent, conformationally constrained antagonist may be a valuable
      pharmacological tool in understanding the structural and topographical
      requirements of peptide ligand binding to the delta-opioid receptors.

PMID- 18068763
TI  - A TLR9 homolog that is up-regulated by IFN-gamma in Atlantic salmon (Salmo
      salar).
AB  - Members of the Toll-like receptor family 9 (TLR9) subfamily sense viral and
      bacterial DNA present in the endosomal compartment. Here we describe the cloning
      and regulation of a TLR9 gene from Atlantic salmon (Salmo salar). The salmon TLR9
      cDNA encodes 1075 amino acids and analysis of the inferred protein sequence shows
      that several amino acid residues known to be important for the functions of TLR9
      in mammals are conserved in salmon. Furthermore, TLR9 expression was elevated in
      head kidney leukocytes after in vitro treatment with CpG ODNs and recombinant
      trout interferon (IFN)-gamma. IFN-gamma was the strongest inducer of TLR9
      expression. Together, the results indicate that the structure, the expression and
      possibly the function of TLR9 are conserved across the teleost and mammalian
      lineages.

PMID- 18068764
TI  - A speciation methodology to study the contributions of humic-like and fulvic-like
      acids to the mobilization of metals from compost using size exclusion
      chromatography-ultraviolet absorption-inductively coupled plasma mass
      spectrometry and deconvolution analysis.
AB  - High performance size-exclusion chromatography (HP-SEC) with UV absorption for
      organic matter detection and inductively coupled plasma mass spectrometry (ICP
      MS) for elemental detection have been used to study the mobilization of metals
      from compost as a function of pH and the molecular mass of their complexes with
      dissolved organic matter (DOM). Due to its heterogeneous nature, organic matter
      mobilized from compost shows a continuous distribution of molecular masses in the
      range studied (up to 80kDa). In order to differentiate between the contribution
      of humic and fulvic acids (FA) to the organic matter mobilized in the pH range 5
      10, their UV absorption chromatographic profiles have been deconvoluted with
      respect to the adjusted gaussian profiles of the humic and fulvic acids isolated
      from compost. Results show a preponderant contribution of fulvic acids at low pH
      values and an increasing percentage of humic acids (HA) mobilized at basic pH (up
      to 49% of total DOM at pH 10). A similar deconvolution procedure has been applied
      to the ICP-MS chromatograms of selected metals (Co, Cu, Pb and Bi). In general,
      both fulvic and humic acids contribute to the mobilization of divalent transition
      metals, such as copper or cobalt, whereas bismuth or lead are preferably
      associated to humic acids. Non-humic substances (HS) also contribute to the
      mobilization of cations, especially at acidic pHs. These conclusions have been
      extended to different elements based on deconvolution analysis results at pH 7.

PMID- 18068765
TI  - Optimization and comparison of chemical and electrochemical hydride generation
      for optical emission spectrometric determination of arsenic and antimony using a
      novel miniaturized microwave induced argon plasma exiting the microstrip wafer.
AB  - Continuous flow (CF) chemical hydride generation (CHG) and electrochemical
      hydride generation (ECHG) directly coupled to a novel 40W, atmospheric pressure,
      2.45GHz microwave microstrip Ar plasma exiting a microstrip wafer has been
      developed for the emission spectrometric determination of As and Sb using a
      miniaturized optical fiber spectrometer and a CCD-array detector. The
      experimental conditions for both procedures were optimized with respect to the
      relative net intensities of the As I 228.8 nm and Sb I 252.8 nm lines and their
      signal-to-background intensity ratios. Additionally, the susceptibility to
      interferences from Cd, Co, Cr, Cu, Fe, Ni, Pb and Zn and other hydride-forming
      elements in the determination of As and Sb using the CHG and ECHG techniques was
      investigated in detail. Under the optimized conditions, it was found that ECHG is
      more prone to interferences compared to CHG. The detection limits (3sigma) of As
      (6 ngmL(-1)) and Sb (7 ngmL(-1)) obtained for the ECHG-MSP-OES method are about
      three times lower than in the case of the CHG-MSP-OES method due to a two-fold
      lower amount of H2 introduced into the MSP in case of the ECHG, resulting in a
      better plasma stability and reduced background level. The linearity ranges for
      both calibration curves to a concentration of up to 5 microgmL(-1) and a
      precision between 2% and 7% (2 microgmL(-1) and 0.050 microgmL(-1) of As and Sb,
      respectively) were found for both methods. The developed ECHG-MSP-OES method was
      validated for As through the analysis of a certified coal fly ash standard
      reference material (NIST SRM 1633a) after sample dissolution. The derived
      concentration (140+/-8 microgg(-1)) was found to agree well with the certified
      data (145+/-15 microgg(-1)). The method was also successfully applied to the
      analysis of both a galvanic bath sample, which contained Sb and was spiked with
      As, and a tap water sample spiked with both analytes. Recovery rates of 99-101%
      and a Sb concentration of 6.6 microgmL(-1) in the galvanic bath sample were
      revealed. The latter value showed a good agreement with the data obtained from
      ICP-OES analysis, which was also used for validation purpose.

PMID- 18068766
TI  - Synchronous fluorescence and UV-vis spectroscopic studies of interactions between
      the tetracycline antibiotic, aluminium ions and DNA with the aid of the Methylene
      Blue dye probe.
AB  - Synchronous fluorescence spectroscopy (SFS) was applied for the investigation of
      interactions of the antibiotic, tetracycline (TC), with DNA in the presence of
      aluminium ions Al3+. The study was facilitated by the use of the Methylene Blue
      (MB) dye probe, and the interpretation of the spectral data with the aid of the
      chemometrics method, parallel factor analysis (PARAFAC). Three-way synchronous
      fluorescence analysis extracted the important optimum constant wavelength
      differences, deltalambda, and showed that for the TC-Al3+-DNA, TC-Al3+ and MB dye
      systems, the associated deltalambda values were different (deltalambda=80, 75 and
      30 nm, respectively). Subsequent PARAFAC analysis demonstrated the extraction of
      the equilibrium concentration profiles for the TC-Al3+, TC-Al3+-DNA and MB probe
      systems. This information is unobtainable by conventional means of data
      interpretation. The results indicated that the MB dye interacted with the TC-Al3+
      DNA surface complex, presumably via a reaction intermediate, TC-Al3+-DNA-MB,
      leading to the displacement of the TC-Al3+ by the incoming MB dye probe.

PMID- 18068767
TI  - Modelling of chemical fractionation patterns of metals in soils by two-way and
      three-way principal component analysis.
AB  - The 'pseudo-total' contents and the chemical fractionation pattern of eight toxic
      elements (As, Cd, Co, Cu, Cr, Ni, Pb and Zn) have been determined in 12 soil
      samples collected around a coal-fuelled power plant (Velilla del Rio Carrion,
      Spain) by using, respectively, the US-EPA 3051 norm and the modified BCR (SM&T)
      chemical fractionation procedure. The 'pseudo-total' dataset has been analyzed by
      classical two-way principal component analysis (PCA) finding a PC accounting for
      the metal 'pollution' of the area. On the other hand, the three-dimensional
      (samples x metals x fractions) X array obtained after application of the modified
      BCR SM&T procedure, has been studied by matrix augmentation (MA-PCA) and three
      way principal component analysis (3-PCA) using PARAFAC and TUCKER3 models.
      Whereas both MA-PCA and PARAFAC originated two-factor models biased towards the
      different chemical fractionation of the samples, the best TUCKER3 model [1, 2, 2]
      takes into account simultaneously both the 'pseudo-total' contents and the
      chemical fractionation of the soil samples. Therefore, the TUCKER3 originated a
      better representation of the global environmental impact caused by the power
      plant, and the plotting of the soil samples loadings, A1, in the physical space
      allowed to locate the most potentially hazardous areas.

PMID- 18068768
TI  - Speciation of trace metals in natural waters: the influence of an adsorbed layer
      of natural organic matter (NOM) on voltammetric behaviour of copper.
AB  - The influence of an adsorbed layer of the natural organic matter (NOM) on
      voltammetric behaviour of copper on a mercury drop electrode in natural water
      samples was studied. The adsorption of NOM strongly affects the differential
      pulse anodic stripping voltammogram (DPASV) of copper, leading to its distortion.
      Phase sensitive ac voltammetry confirmed that desorption of adsorbed NOM occurs
      in general at accumulation potentials more negative than -1.4V. Accordingly, an
      application of negative potential (-1.6V) for a very short time at the end of the
      accumulation time (1% of total accumulation time) to remove the adsorbed NOM was
      introduced in the measuring procedure. Using this protocol, a well-resolved peak
      without interferences was obtained. It was shown that stripping
      chronopotentiogram of copper (SCP) in the depletive mode is influenced by the
      adsorbed layer in the same manner as DPASV. The influence of the adsorbed NOM on
      pseudopolarographic measurements of copper and on determination of copper
      complexing capacity (CuCC) was demonstrated. A shift of the peak potential and
      the change of the half-peak width on the accumulation potential (for
      pseudopolarography) and on copper concentration in solution (for CuCC) were
      observed. By applying a desorption step these effects vanished, yielding
      different final results.

PMID- 18068769
TI  - Sensitive and stable amperometric measurements at ionic liquid-carbon paste
      microelectrodes.
AB  - Ionic liquids (ILs) were utilized in preparing carbon paste electrodes with
      improved sensitivity, linearity, and stability. In order to overcome the large
      capacitance encountered with these pastes which affects the measured signal,
      microelectrodes were used to minimize the background current and improve the
      signal to background response. A number of ILs were tested including those having
      the same anions, such as butyl, hexyl, and octyl hexafluorophosphate (PF(6)), and
      those having the same cation, including hexyl-imide, trifluorophosphate (PF(3))
      and PF(6). Based on the structure of each ILs, different responses were obtained.
      Several probes were utilized for those studies including hydrogen peroxide,
      acetaminophen, and ascorbic acid. The butyl-methyl-imidazolium (BMI)-PF(6)
      displayed the highest response among other ILs with similar anions and the
      smallest peak separation. The optimum ILs loading in terms of electrode
      resistance, capacitance, and peak separation was 30-40%. Improved resistance to
      surface fouling was observed at the ILs-carbon paste electrode compared to that
      using mineral oil when tested for NADH detection. Very good linearity up to 1mM
      hydrazine (correlation coefficient 0.996) was obtained using the ILs-carbon paste
      electrode.

PMID- 18068770
TI  - Improving prediction selectivity for on-line near-infrared monitoring of
      components in etchant solution by spectral range optimization.
AB  - The components (H3PO4, HNO3, CH3COOH and water) in an etchant solution have been
      accurately measured in an on-line manner using near-infrared (NIR) spectroscopy
      by directly illuminating NIR radiation through a Teflon line. In particular, the
      spectral features according to the change of H3PO4 or HNO3 concentrations were
      not mainly from NIR absorption themselves, but from the perturbation (or
      displacement) of water bands; therefore, the resulting spectral variations were
      quite similar to each other. Consequently partial least squares (PLS) prediction
      selectivity among the components should be the most critical issue for continuous
      on-line compositional monitoring by NIR spectroscopy. To improve selectivity of
      the calibration model, we have optimized the calibration models by finding
      selective spectral ranges with the use of moving window PLS. Using the optimized
      PLS models for each component, the resulting prediction accuracies were
      substantially improved. Furthermore, on-line prediction selectivity was evaluated
      by spiking individual pure components step by step and examining the resulting
      prediction trends. When optimized PLS models were used, each concentration was
      selectively and sensitively varied at each spike; meanwhile, when whole or non
      optimized ranges were used for PLS, the prediction selectivity was greatly
      degraded. This study verifies that the selection of an optimal spectral range for
      PLS is the most important factor to make Teflon-based NIR measurements successful
      for on-line and real-time monitoring of etching solutions.

PMID- 18068771
TI  - Vicinal diaminobenzoacridine used as the fluorescent probe for trace nitric oxide
      determination by flow injection spectrofluorimetry and macrophage cells imaging.
AB  - Based on a photoelectron transfer (PET) mechanism, vicinal diaminobenzoacridine
      (VDABA), a fluorescent probe for the determination of trace amounts of nitric
      oxide radical in biological sample, was synthesized and characterized by
      elemental analysis, IR, (1)H NMR and (13)C NMR spectrum. Combining a flow
      injection with spectrofluorimetry, a high-throughput method for detecting NO was
      obtained, which was successfully applied to the determination of NO in the human
      serum. The proposed method was simple, rapid, precise and automatic. Under
      optimum conditions, the linear calibration range was from 1.1 x 10(-7) to 5.0 x
      10(-6)M and the detection limit was 3.1 x 10(-8)M. Furthermore, the probe could
      make cell-derived NO "visible" by using confocal laser scanning microscope.

PMID- 18068772
TI  - A high-precision ratiometric fluorosensor for pH: implementing time-dependent non
      linear calibration protocols for drift compensation.
AB  - We present a versatile time-dependent non-linear calibration protocol for optical
      sensors, implemented on the pH sensitive ratiometric fluorophore 8-hydroxypyrene
      1,3,6-trisulfonic acid (HPTS) immobilized in ethyl-cellulose. The calibration
      protocol individually compensated for the progressive drift of calibration
      parameters, whereby sensor precision and accuracy, as well as applicable lifetime
      were improved. A severely reduced photoacidity was observed for the immobilized
      fluorophore, for which excited state dynamics was characterized and benefited
      from during measurements. Due to the significantly reduced photoacidity of HPTS
      immobilized in the ethyl-cellulose sensing membrane, a dual excitation/dual
      emission (F(1), ex/em: 405/440 nm and F(2), ex/em: 465/510 nm) ratiometric
      (R(F(1), F(2) =F(1)/F(2)) sensing scheme could be used to amplify sensor
      response. The signal to noise (S/N) ratio was enhanced by approximately 400%
      utilizing the dual excitation/dual emission ratiometric sensing scheme, rather
      than the more commonly used protocol of dual excitation/single emission for HPTS
      fluorescence. Apparent pK(a) of the fluorophore ranged from 6.74 to 8.50, mainly
      determined by the immobilization procedure. The repeatability (IUPAC, pooled
      standard deviation) over three pH values (6.986, 7.702 and 7.828) was 0.0044 pH
      units for the optical sensor, compared to 0.0046 for the electrode used for
      standardization. Sensor analytical characteristics were thereby in principle
      limited by the performance of the standardization procedure.

PMID- 18068773
TI  - Particulate and soluble Eu(III)-chelates as donor labels in homogeneous
      fluorescence resonance energy transfer based immunoassay.
AB  - Many well-established homogeneous separation free immunoassays rely on
      particulate label technologies. Particles generally contain a high concentration
      of the embedded label and they have a large surface area, which enables
      conjugation of a large amount of protein per particle. Eu(III)-chelate dyed
      nanoparticles have been successfully used as labels in heterogeneous and
      homogeneous immunoassays. In this study, we compared the characteristics of two
      homogeneous competitive immunoassays using either soluble Eu(III)-chelates or
      polystyrene particles containing Eu(III)-chelates as donors in a fluorescence
      resonance energy transfer based assay. The use of the particulate label
      significantly increased the obtained sensitized emission, which was generated by
      a single binding event. This was due to the extremely high specific activity of
      the nanoparticle label and also in some extent the longer Forster radius between
      the donor and the acceptor. The amount of the binder protein used in the assay
      could be decreased by 10-fold without impairing the obtainable sensitized
      emission, which subsequently led to improved assay sensitivity. The optimized
      assay using particulate donor had the lowest limit of detection (calculated using
      3 x S.D. of the 0 nM standard) 50pM of estradiol in the assay well, which was
      approximately 20-fold more sensitive than assays using soluble Eu(III)-chelates.

PMID- 18068774
TI  - Enantioselective analysis of mirtazapine and its two major metabolites in human
      plasma by liquid chromatography-mass spectrometry after three-phase liquid-phase
      microextraction.
AB  - A three-phase liquid-phase microextraction (LPME) method using porous
      polypropylene hollow fibre membrane with a sealed end was developed for the
      extraction of mirtazapine (MRT) and its two major metabolites, 8
      hydroxymirtazapine (8-OHM) and demethylmirtazapine (DMR), from human plasma. The
      analytes were extracted from 1.0 mL of plasma, previously diluted and alkalinized
      with 3.0 mL 0.5 molL(-1) pH 8 phosphate buffer solution and supplemented with 15%
      sodium chloride (NaCl), using n-hexyl ether as organic solvent and 0.01 moLL(-1)
      acetic acid solution as the acceptor phase. Haloperidol was used as internal
      standard. The chromatographic analyses were carried out on a chiral column, using
      acetonitrile-methanol-ethanol (98:1:1, v/v/v) plus 0.2% diethylamine as mobile
      phase, at a flow rate of 1.0 mLmin(-1). Multi-reaction monitoring (MRM) detection
      was performed by mass spectrometry (MS-MS) using a triple-stage quadrupole and
      electrospray ionization interface operating in the positive ion mode. The mean
      recoveries were in 18.3-45.5% range with linear responses over the 1.25-125 ngmL(
      1) concentration range for all enantiomers evaluated. The quantification limit
      (LOQ) was 1.25 ngmL(-1). Within-day and between-day assay precision and accuracy
      (2.5, 50 and 100 ngmL(-1)) showed relative standard deviation and the relative
      error lower than 11.9% for all enantiomers evaluated. Finally, the method was
      successfully used for the determination of mirtazapine and its metabolite
      enantiomers in plasma samples obtained after single drug administration of
      mirtazapine to a healthy volunteer.

PMID- 18068775
TI  - Molecularly imprinted polymer using beta-cyclodextrin as functional monomer for
      the efficient recognition of bilirubin.
AB  - Bilirubin (BR) imprinted polymer was successfully prepared using supramolecular
      host compound beta-cyclodextrin (beta-CD) as functional monomer. The adsorption
      equilibrium was attained in about 4 h, which indicated that the adsorption
      kinetics was comparatively fast. The results of adsorption and selectivity
      experiments indicated that BR-imprinted beta-CD polymer was able to bind BR
      specifically and reversibly. The specific recognition of BR-imprinted beta-CD
      polymer for BR may be due to the cooperative effects of inclusion interaction and
      hydrogen bonding. This BR-imprinted beta-CD polymer was further applied to
      eliminate BR in human serum sample. It was verified that the binding specificity
      of the BR-imprinted polymer for BR was essentially sufficient in the presence of
      other compounds coexisting in serum sample. Therefore, as a reusable material
      possessing high affinity and selectivity, BR-imprinted beta-CD polymer has a
      potential application perspective as a clinical hemoperfusion material.

PMID- 18068776
TI  - Multiplexed high-throughput electrokinetically-controlled immunoassay for the
      detection of specific bacterial antibodies in human serum.
AB  - In previous studies we have developed a simple electrokinetically-controlled lab
      on-a-chip for heterogeneous immunoassay. In that method, all the sequential
      operations in an immunoassay, such as reagent loading and washing, were performed
      automatically by electrokinetically controlling the flow in an H-shaped
      microchannel. Here, we demonstrated further development of a high-throughput
      immunoassay microfluidic chip, and the application of the new immunoassay
      microfluidic chip in assaying human serum. The microfluidic immunoassay analyzed
      ten samples in parallel in 22 min. Bacterial antibodies in samples were captured
      by antigens pre-patterned on the bottom wall of a microchannel and then bound
      with TRITC-labeled detection antibodies to generate fluorescent signals. With
      optimized surface concentration of antigen, the assay detected Escherichia coli
      O157:H7 antibody and Helicobacter pylori antibody from buffer solutions in
      concentration ranges of 0.02-10 microgmL(-1) and 0.1-50 microgmL(-1),
      respectively. Human sera that were E. coli-positive or H. pylori-positive were
      accurately distinguished from respective negative controls. Moreover, the two
      antibodies, anti-E. coli and anti- H. pylori antibodies, could be simultaneously
      detected from human serum. This electrokinetically-controlled immunoassay shows
      an excellent potential for efficiently detecting multiple pathogenic infections
      in clinical environments.

PMID- 18068777
TI  - The design and characteristics of direct current glow discharge atomic emission
      source operated with plain and hollow cathodes.
AB  - A compact direct current glow discharge atomic emission source has been designed
      and constructed for analytical applications. This atomic emission source works
      very efficiently at a low-input electrical power. The design has some features
      that make it distinct from that of the conventional Grimm glow discharge source.
      The peculiar cathode design offered greater flexibility on size and shape of the
      sample. As a result the source can be easily adopted to operate in Plain or
      Hollow Cathode configuration. I-V and spectroscopic characteristics of the source
      were compared while operating it with plain and hollow copper cathodes. It was
      observed that with hollow cathode, the source can be operated at a less input
      power and generates greater Cu I and Cu II line intensities. Also, the intensity
      of Cu II line rise faster than Cu I line with argon pressure for both cathodes.
      But the influence of pressure on Cu II lines was more significant when the source
      is operated with hollow cathode.

PMID- 18068778
TI  - Prediction of soluble solids content, firmness and pH of pear by signals of
      electronic nose sensors.
AB  - The objective of this study was to investigate the predictability of an
      electronic nose for fruit quality indices. Responses signal of sensor array in
      electronic nose were employed to establish quality indices model for "xueqing"
      pear. The relationships were established between signal of electronic nose and
      the quality indices of fruit (firmness, soluble solids content (SSC) and pH) by
      multiple linear regressions (MLR) and artificial neural network (ANN). The
      prediction models for firmness and soluble solids content indicated a good
      prediction performance. The SSC model by ANN had a standard error of prediction
      (SEP) of 0.41 and correlation coefficient 0.93 between predicted and measured
      values, the model by ANN for the penetrating force (CF) had a 3.12 SEP and 0.94
      coefficient, respectively. The results imply that it is possible to predict
      "xueqing" pear quality characteristics from signal of E-nose.

PMID- 18068779
TI  - Distribution of intraperitoneally injected diclofenac in brown trout (Salmo
      trutta f. fario).
AB  - The detection of low levels of pharmaceuticals in aquatic environments has lately
      raised concerns regarding possible adverse effects of these highly active
      substances on aquatic organisms. The non-steroidal anti-inflammatory drug
      diclofenac (DCF) is one of the pharmaceutical substances regularly detected in
      surface waters and has lately been demonstrated to elicit adverse effects in
      salmonid species at environmentally relevant concentrations. The aim of the
      present study was to investigate the distribution of DCF in indigenous brown
      trout (Salmo trutta f. fario) following intraperitoneal (i.p.) injection of a
      single dose of (14)C-labelled DCF. A distribution kinetic over 36 h provides
      information on possible accumulation of DCF in different organs as well as on DCF
      detoxification in trout, possibly enabling identification of sites of
      preferential toxicity. Approximately 57% of the total single DCF dose appeared in
      the bile 6 h after i.p. application. Subsequently, DCF was observed to undergo
      enterohepatic cycling with an amount of (14)C-activity comparable to the 6 h bile
      values reappearing in bile 36 h after application. Results for (14)C-activity in
      intestine and pylori support the observation of enterohepatic cycling with a
      small peak in intestine at 3 h post i.p. injection and a low peak in intestine
      and pylori at 6 h post i.p. injection, reflecting presence of the drug substance
      in bile. The highest activity in intestine was found 24 h post-injection
      coinciding with low levels in bile, followed by a gradual decrease of activity in
      intestine mirroring the re-uptake of DCF into bile. The finding of enterohepatic
      cycling of DCF in brown trout is suggestive of a prolonged retention of DCF in
      brown trout.

PMID- 18068780
TI  - Effects of transgenic corn and Cry1Ab protein on the nematode, Caenorhabditis
      elegans.
AB  - The effects of the insecticidal Cry1Ab protein from Bacillus thuringiensis (Bt)
      on the nematode, Caenorhabditis elegans, were studied with soil from experimental
      fields cultivated with transgenic Bt corn (MON810) and with trypsinized Cry1Ab
      protein expressed in Escherichia coli. The content of Cry1Ab protein was above
      the detection limit of an ELISA test in only half of the soil samples obtained
      from transgenic plots, ranging from 0.19 to 1.31 ng g(-1) dry weight. In a
      laboratory bioassay, C. elegans was exposed to rhizosphere and bulk soil from
      fields with isogenic or transgenic corn or to solutions of Cry1Ab protein (0, 24,
      41, 63, 118, and 200 mg l(-1)) over a period of 96 h, with growth and
      reproduction serving as the test parameters. Nematode reproduction and growth
      were significantly reduced in rhizosphere and bulk soil of Bt corn compared with
      soil from isogenic corn and were significantly correlated with concentrations of
      the Cry1Ab protein in the soil samples. Moreover, the toxicity of pure Cry1Ab
      protein to the reproduction and growth of C. elegans was concentration-dependent.
      As significant inhibition occurred at relatively high concentrations of the
      Cry1Ab protein (41 mg l(-1)), the effects of the soil samples from Bt corn could
      not be assigned directly to the toxicity of the Cry1Ab protein. The results
      demonstrate that bioassays with the nematode, C. elegans, provide a promising
      tool for monitoring the potential effects of Bt toxins in aqueous medium and
      soils.

PMID- 18068781
TI  - Toxicity interactions of cadmium, copper, and lead on soil urease and
      dehydrogenase activity in relation to chemical speciation.
AB  - The toxicity of the trace metals Cd, Cu, and Pb alone and in combination was
      assessed by measuring the activity of the soil enzymes dehydrogenase and urease.
      We assayed the enzymatic response of a forest soil exposed to single metals and
      metal mixtures in a factorial design. The chemical speciation of the metals was
      measured in 0.01M KNO3 solution extracts using an ion-selective electrode for
      Cu2+ and estimated from voltammetric determinations of labile metals for Cd2+ and
      Pb2+. The toxicity interaction of the metal mixtures was predicted according to
      the classical Bliss independence and Loewe additivity models. Significant
      antagonistic effects were observed for the majority of the combinations for both
      the dehydrogenase and the urease assays. Given the strong interaction upon the
      chemistry, the toxicity interaction data were analyzed based on resulting free
      metal activities to tease out the effect of chemistry changes from that of
      toxicological responses. As a result, a stimulation of enzymatic activities was
      observed in the mixtures in comparison to the enzymatic activities obtained with
      the individual metal.

PMID- 18068782
TI  - Protein folding: are we there yet?

PMID- 18068783
TI  - The relationship of climatic and hydrological parameters to surface water quality
      in the lower Mekong River.
AB  - The relationship between climatic, hydrological and water quality parameters of
      the lower Mekong River flowing through four different countries (Thailand,
      Cambodia, Lao PDR and Vietnam) was studied. The Mekong River Commission (MRC)
      secondary data of climatic and hydrological parameters included precipitation,
      evaporation, average air temperatures, mean water level and discharge flow. Water
      quality parameters consisted of TSS, NO(3)(-), PO(4)(3-), DO, pH, conductivity,
      Ca, Mg, Na, K, alkalinity, Cl, SO(4)(2-), Fe, TP, Si and COD. Pearson's
      correlation was used to determine their relationship. The results reveal that the
      correlations of climatic, hydrological and water quality parameters in those four
      countries located along the lower Mekong River had the same trend. Precipitation
      had fair positive correlations with mean water level (ranging 0.375-0.661),
      discharge flow (ranging 0.526-0.659) and mean air temperature (ranging 0.515
      0.621), however had weak negative correlation with evaporation (ranging 0.169
      0.468). Concerning relationship with water quality, the results show that TSS,
      NO(3)(-), PO(4)(3-), TP and COD had weak to fair positive correlations with
      precipitation, mean water level, discharge flow. However, DO, pH, conductivity,
      Ca, Mg, Na, K, alkalinity, Cl, SO(4)(2-) and Si had fair to strong negative
      correlations with all hydrological parameters. Finally, TSS, alkalinity and
      conductivity were proposed as sensitive water quality parameters for monitoring
      impacts of changing climate in the lower Mekong River.

PMID- 18068784
TI  - Imaging appearances following thermal ablation.
AB  - Radiofrequency ablation (RFA) has an increasingly important role in the
      management of a number of solid tumours. Treatments usually take place at
      specialist centres that draw patients from a wide geographical area, but follow
      up imaging is often undertaken at the referring institution. This review aims to
      describe and illustrate the range of normal and abnormal post-ablative
      appearances encountered in the most commonly treated organs, i.e. liver, lung,
      and kidney, to equip radiologists with the necessary knowledge for confident
      interpretation of post-ablation imaging in this diverse patient group.

PMID- 18068785
TI  - Work-based assessment for trainees -- more than just a few new tools?

PMID- 18068786
TI  - Finding and maintaining professionalism in radiology.

PMID- 18068787
TI  - Imaging of obstructed defecation.
AB  - Constipation is a common problem in the western world, which occurs as a
      consequence of impaired colonic transit and/or due to obstructed defecation.
      Imaging plays an important role in distinguishing structural from functional
      causes of constipation. In this article a description of common imaging
      techniques for diagnosing structural causes of constipation with illustrations of
      abnormal defecographic findings in patients with obstructive defecation are
      presented.

PMID- 18068788
TI  - Slipped upper femoral epiphysis: imaging of complications after treatment.
AB  - Slipped upper femoral epiphysis (SUFE) is a multifactorial condition usually
      affecting adolescents. Obesity is one risk factor, and as this is increasing the
      incidence of SUFE is likely to rise. Diagnosis and treatment are usually
      straightforward and carried out by orthopaedic surgeons. However, the recognition
      of post-treatment complications poses a much greater challenge. This article
      focuses on possible complications of surgical treatment of SUFE particularly.
      Chondrolysis, avascular necrosis, as well as other complications of treatment and
      conditions leading to premature osteoarthritis are discussed. Checklists for a
      systematic approach to post-treatment imaging are provided.

PMID- 18068789
TI  - Lung lesion doubling times: values and variability based on method of volume
      determination.
AB  - PURPOSE: To determine doubling times (DTs) of lung lesions based on volumetric
      measurements from thin-section CT imaging. METHODS: Previously untreated patients
      with > or = two thin-section CT scans showing a focal lung lesion were
      identified. Lesion volumes were derived using direct volume measurements and
      volume calculations based on lesion area and diameter. Growth rates (GRs) were
      compared by tissue diagnosis and measurement technique. RESULTS: 54 lesions were
      evaluated including 8 benign lesions, 10 metastases, 3 lymphomas, 15
      adenocarcinomas, 11 squamous carcinomas, and 7 miscellaneous lung cancers. Using
      direct volume measurements, median DTs were 453, 111, 15, 181, 139 and 137 days,
      respectively. Lung cancer DTs ranged from 23-2239 days. There were no significant
      differences in GRs among the different lesion types. There was considerable
      variability among GRs using different volume determination methods. CONCLUSIONS:
      Lung cancer doubling times showed a substantial range, and different volume
      determination methods gave considerably different DTs.

PMID- 18068790
TI  - MRI of early symptomatic metal-on-metal total hip arthroplasty: a retrospective
      review of radiological findings in 20 hips.
AB  - AIM: To perform a retrospective review of all the conventional radiographic and
      magnetic resonance imaging (MRI) studies performed in patients with early
      postoperative pain following cobalt-chrome metal-on-metal total hip arthroplasty.
      METHODS: A retrospective review of the radiology, surgical findings and histology
      in nineteen patients who had undergone a total of 20 hip arthroplasties using a
      cobalt-chromium on cobalt-chromium alloy prosthesis was undertaken. RESULTS:
      Measures of implant placement on the immediate postoperative radiographs were all
      within the normal ranges (n=20). Where more than one postoperative radiograph was
      available statistical analysis revealed no evidence of progressive change before
      the MRI examination (14). The median postoperative time to MRI was 35 months
      (range 11-63 months). Abnormalities were demonstrated using MRI in all
      symptomatic hips (n=20). These comprised: periprosthetic fluid collections (20),
      which were isointense to muscle on T1-weighted images in 19 cases and
      hyperintense on T2-weighted images in 18 cases, periprosthetic bone marrow oedema
      (n=6), muscle oedema (n=4), avulsion of the gluteus minimus and medius tendons
      (n=5), atrophy of piriformis (n=15) and obturator internus (n=17), and fracture
      of the medial calcar (n=1). Operative findings in patients who had undergone
      revision surgery (n=15) included: fluid-filled cavities (n=11), soft tissue
      necrosis (n=8), gluteal tendon avulsion (n=5), proximal femoral diaphyseal
      necrosis (n=4), and pitting and corrosion of the femoral stems (n=8), which were,
      in all cases, firmly fixed to the cement mantle. Histology revealed viable tissue
      in six hips with necrosis (n=12) and fibrin deposition (n=15) being the
      predominate findings. Other findings included a perivascular lymphocytic
      infiltrate (n=5), features of active inflammation (n=4), and metallosis (n=1).
      CONCLUSION: A significant number of patients with metal-on-metal hip replacements
      presented with early postoperative pain because of an abnormal soft-tissue
      reaction. MRI can demonstrate characteristic soft-tissue disease in these
      patients where conventional radiographs are frequently normal.

PMID- 18068791
TI  - Acute bone crises in sickle cell disease: the T1 fat-saturated sequence in
      differentiation of acute bone infarcts from acute osteomyelitis.
AB  - AIM: To prove the hypothesis that acute bone infarcts in sickle cell disease are
      caused by sequestration of red blood cells (RBCs) in bone marrow, and to evaluate
      the unenhanced T1 fat-saturated (fs) sequence in the differentiation of acute
      bone infarction from acute osteomyelitis in patients with sickle-cell disease.
      MATERIALS AND METHODS: Two studies were undertaken: an experimental study using
      in-vitro packed red blood cells and normal volunteers, and a retrospective
      clinical study of 86 magnetic resonance imaging (MRI) studies. For the
      experimental study containers of packed RBCs were placed between the knees of
      four healthy volunteers with a saline bag under the containers as an additional
      control, and were scanned with the pre-contrast T1-fs sequence. Signal intensity
      (SI) ratios were obtained for packed RBCs:skeletal muscle and packed RBCs:saline.
      For the clinical study, the SIs of normal bone marrow, packed RBCs, bone and/or
      soft-tissue lesions, and normal skeletal muscle of 74 patients (86 MRI studies)
      were measured using unenhanced, T1 fat-saturated MRI. The ratios of the above SIs
      to normal skeletal muscle were calculated and subjected to statistical analysis.
      RESULTS: Fifty-one of 86 MRI studies were included in the final analysis. The
      ratios of SIs for normal bone marrow, packed red cells, bone infarction, acute
      osteomyelitis, and soft-tissue lesions associated with bone infarct, compared
      with normal skeletal muscle were (mean+/-SD) 0.9+/-0.2, 2.1+/-0.7, 1.7+/-0.5,
      1.0+/-0.3, and 2.2+/-0.7, respectively. The difference in the ratio of SIs of
      bone infarcts and osteomyelitis was significant (p=0.003). The final diagnoses
      were bone infarction (n=50), acute osteomyelitis (n=1), and co-existent bone
      infarction and osteomyelitis (n=2). Seven patients who had suspected
      osteomyelitis underwent image-guided aspiration. CONCLUSION: Acute bone infarcts
      in sickle cell disease are caused by sequestration of red blood cells in the bone
      marrow. The unenhanced, T1-fat-saturated sequence alone is diagnostic for acute
      bone infarcts. Contrast enhancement aids in the diagnosis of acute osteomyelitis.
      MRI can thus help in early diagnosis, specific treatment, and preventing
      empirical antibiotic therapy.

PMID- 18068792
TI  - Biphosphonate-induced osteonecrosis of the jaws: CT and MRI spectrum of findings
      in 32 patients.
AB  - AIM: To evaluate the computed tomography (CT) and magnetic resonance imaging
      (MRI) findings of biphosphonate therapy-associated changes of the mandible and
      maxilla. MATERIALS AND METHODS: Thirty-two patients with a clinical history of
      pain, purulent discharge, and swelling in the mandible or maxilla as well as non
      healing dental extraction were examined. All patients had received biphosphonate
      medication for approximately 33 months. Non-contrast enhanced CT and contrast
      enhanced MRI were performed and, subsequently, all patients underwent a surgical
      removal of the affected bone, the histological diagnosis of which confirmed
      osteonecrosis. The images were read by two head and neck radiologists in
      consensus. RESULTS: Osteonecrosis with Actinomyces infection was identified in
      the mandible of 18 patients, in the maxilla of eight patients, and in both jaws
      in six patients. The CT images showed predominantly osteolytic lesions and
      sclerotic regions in the jaws with or without periostal bone proliferation. There
      was a reduction of the marrow space in the jaws. The T1-weighted MRI signal was
      hypointense in nearly all cases. The gadolinium-enhanced MRI images revealed
      intensity changes of the cortical and subcortical bone structures in all
      patients. The T2-weighted MRI signal was hypointense on the affected side in the
      majority of the cases (28/32). Pathological gadolinium enhancement was observed
      in the neighbouring soft tissues, including the masticator space in all patients.
      Reactive lymphadenopathy was found in all patients in submental and
      jugulodigastric areas. CONCLUSION: Biphosphonate-induced osteonecrosis of the
      jaws presents a wide variety of CT and MRI features that are readily recognized
      and help to determine the extent of the disease; however, they are not specific
      for the disease.

PMID- 18068793
TI  - Biphosphonate-induced osteonecrosis of the jaws: CT and MRI spectrum of findings
      in 32 patients.

PMID- 18068794
TI  - Intracranial ganglioglioma: clinicopathological and MRI findings in 16 patients.
AB  - AIM: To record the clinical findings and magnetic resonance imaging (MRI)
      characteristics of intracranial gangliogliomas in 16 patients. MATERIALS AND
      METHODS: Sixteen patients were imaged using unenhanced and contrast-enhanced MRI.
      Eight patients underwent unenhanced CT and of these, three underwent contrast
      enhanced CT. Two radiologists read the images retrospectively. The images were
      studied with regard to location, size, margin, signal intensity, enhancement
      characteristics, cystic changes, and presence of calcifications. Clinical data,
      such as presenting signs and symptoms, physical findings, and medical histories,
      were collected. Histopathological and immunohistochemical studies were performed
      and analysed by two pathologists. RESULTS: In 12 cases the tumours were located
      in one of the cerebral hemispheres; in the other cases they were located in the
      brainstem, cerebellum, suprasellar area or the thalamus. The tumour dimension
      varied from 1-7 cm, with a mean of 3.6 cm+/-1.8 cm. The MRI features of
      ganglioglioma in the present cohort can be divided into three patterns: cystic
      (n=2), cystic-solid (n=6), and solid (n=8). Solid lesions had a predilection for
      the temporal lobe; cystic and cystic-solid tumours had a wide anatomical
      distribution. Cystic lesions were significantly smaller than both cystic-solid
      and solid lesions (F=4.28, P<0.05). Cystic changes in the cystic-solid tumours
      showed one of the following patterns: those with walls showing contrast
      enhancement, those containing an enhancing nodule, or cysts without an obvious
      wall. The solid portion of cystic-solid gangliogliomas and the entire tumour in
      solid tumours showed homogeneous enhancement of variable degrees on T1-weighted
      (T1W) spin-echo (SE) images. Five tumours had mild or moderate oedema. In one
      patient two separate gangliogliomas were found, each lesion exhibiting different
      MRI features: solid and cystic-solid. One case of cortical ganglioglioma was
      found, causing bone erosion due to pressure. One tumour with chronic haemorrhage
      was found in the study. CONCLUSION: MRI features of gangliogliomas are non
      specific. A ganglioglioma should be suspected when a tumour shows the following
      features: (1) a solid lesion located in the temporal lobes with mild or no oedema
      and homogeneous enhancement on SE T1W images; or (2) a small cystic lesion or
      cystic-solid mixed mass with a wall enhancement or a markedly enhanced nodule. We
      report a patient with two separate gangliogliomas and a case with bone erosion.

PMID- 18068795
TI  - "Fallen fragment sign" in Langerhans' cell histiocytosis.

PMID- 18068796
TI  - A novel radiological appearance of meningeal extranodal marginal-zone B-cell
      lymphoma.

PMID- 18068797
TI  - Giant cell tumour of soft tissue causing oncogenic osteomalacia: report
      demonstrating the use of octreotide scintigraphy in tumour localization.

PMID- 18068798
TI  - Re: 'PET-CT in non-small cell lung cancer staging-promises and problems'.

PMID- 18068799
TI  - A limited skeletal survey may be a better screening tool than isotope bone
      scinitgraphy when imaging Paget's disease of the bone; an inconvenient truth?

PMID- 18068800
TI  - Gene expression profiling of suppressor mechanisms in tuberculosis.
AB  - Mycobacterium tuberculosis (M.tb) infects 8 million and kills 2.2 million people
      each year worldwide. M.tb modulates the immune response of the infected
      individual. Empirically, suppressor carbohydrates (SC) produced by CD8+ T cells
      in response to M.tb were found to induce a T helper 2 response rather than a
      protective T helper 1 response in human mononuclear (MN) cells. This study (1)
      identifies the genes that modulate the T helper response, (2) describes their
      function, and (3) postulates a detailed model for the M.tb infection mechanism.
      MN cells from five healthy donors were pulsed with SC and gene expression
      profiles of 18,861 genes were assessed in a micro-array experiment. Twenty-eight
      genes were found to be increased and 60 genes were decreased (FDR=1%, fold
      change>1.4) in response to SC. MIP3 alpha and platelet factor 4 (v1) are both
      significantly enriched (p< or =0.001) in the GO category "chemokine activity".
      Repressed genes were significantly (p< or =0.001) over-represented in the GO
      terms "response to pathogenic bacteria", "inflammatory response", "coagulation"
      and "apoptosis". Indeed, SC significantly reduced numbers of Annexin V/CD4+
      cells, while inducing hypoproliferation in CD4+ and non-adherent lymphocytes.
      This may indicate that M.tb renders a portion of the CD4+ T cell population
      unresponsive. Furthermore, validating QRT-PCR analysis suggests that monocytes
      provide an immuno-modulatory signal to CD4+ T cells in M.tb infection. These
      observations will allow development of new therapeutic interventions to restore
      the desired T helper 1 response.

PMID- 18068802
TI  - Best practices for the treatment of patients with mental and substance use
      illnesses in the emergency department.

PMID- 18068803
TI  - Chelation of UO2(2+) and Th(IV) by N,N'-bis(pyridoxylideneiminato)R (R=n-propyl,
      diethylamine), new dianionic Schiff bases derived from vitamin B6: Synthesis and
      structural features of [Th(pyr2pen)2] (pen=1,3-propylendiamine),
      [UO2(pyr2pen)(CH3OH)] and [UO2(pyr2dien)].2H2O (dien=diethylenetriamine).
      Searching further modelings for heavy metals damage inhibition in living beings.
AB  - Th(NO(3))(4).5H(2)O reacts with H(2)pyr(2)pen {propylenediamine
      bis(pyridoxylideneimine)}, UO(2)(NO(3))(2).6H(2)O reacts with H(2)pyr(2)pen and
      H(2)pyr(2)dien {diethylenetriamine-bis(pyridoxylideneimine)} under deprotonation
      of the endo hydroxyl groups of the Schiff bases rings to give the chelate
      complexes [Th(pyr(2)pen)(2)] (1), [UO(2)(pyr(2)pen)(CH(3)OH)] (2) and
      [UO(2)(pyr(2)dien)].2H(2)O (3). In 1 the thorium center is the common vertex of
      two square pyramids displaced on 45 degrees to each other. In 2 and 3 the uranium
      atoms are the centers of distorted pentagonal bipyramides. In 2 a methanol
      molecule achieves the coordination number 7 of the uranium(VI) ion, in 3 the
      central N atom of the dien section of the ligand accomplishes the coordination
      polyhedra, resulting a chelate complex with remarkable higher symmetry. Some
      radiological factors are also discussed, correlating the knowledges of new
      chemical properties of uranium and thorium with the understanding of its
      metabolism in living beings, what, in principle, should give support for clinical
      studies about prevention, diagnosis and treatment of uranium, thorium and/or
      heavy metals poisoning.

PMID- 18068804
TI  - Dynamic multi-arm radial lens stretcher: a robotic analog of the ciliary body.
AB  - We developed a dynamic lens stretching device to quantitatively determine the
      relationships between force, equatorial displacement, and anterior curvature. A
      computer-controlled four-arm lens stretcher, equipped with real-time force
      transducers in each arm, was designed and constructed to obtain transient force
      measurements during lens stretching. The force-decay spectrum was fitted with a
      seven-parameter viscoelastic model characterized by three time constants. A
      corneal topography unit was used to measure the curvature of fresh porcine lenses
      ex vivo and in vitro in a four-arm lens stretcher at various equatorial
      displacements. The lens stretcher and corneal topography unit provided detailed
      information regarding the behavior of the porcine lens in vitro. For all lenses,
      the central portion of the anterior surface flattened as zonular force increased.
      Force increased nonlinearly with equatorial displacement. Relaxation time
      constants for accommodation were 34.5+/-12.2 ms, 310+/-122 ms, and 12,800+/-9490
      ms. Time constants for disaccommodation were 34.9+/-4.7 ms, 291+/-79.1 ms, and
      3400+/-775 ms, which were not statistically different from those measured for
      accommodation. The lens stretcher acts as a robotic analog of the ciliary body.
      This device allows direct, quantitative measurement of the forces and curvature
      changes relevant to accommodation. However, distortions were present due to the
      use of only four arms.

PMID- 18068805
TI  - Hospital-based study of viridans streptococcal bacteraemia in children and
      adults.
AB  - OBJECTIVES: To assess the proportion and clinical significance of bacteraemia
      caused by viridans streptococci (VS) in immunocompetent adults and children.
      METHODS: Over a 25-month period, we collected data on all patients with VS
      bacteraemia at a UK district general hospital. RESULTS: VS caused 50/723 (6.9%)
      adult and 13/106 (12.3%) paediatric community-acquired bacteraemias. Of the 43
      adult and 12 paediatric patient notes reviewed, 26 (47.3%) cultures were of
      'definite' or 'probable' clinical significance. No patients were neutropenic and
      overall penicillin resistance was 11/55 (20.0%). Amongst adults, there were five
      (11.6%) confirmed or suspected cases of infective endocarditis compared to none
      in the paediatric cohort. Similar proportions of adults (16.3%) and children
      (16.7%) had lower respiratory tract infections. Among non-significant cultures, a
      history of seizures was observed in one (1.3%) adult and four (33.3%) children
      (p=0.008). Thirty-day mortality was 7.3%. No children and four adults died, one
      directly attributable to infection. Median adult inpatient stay was 11 days
      compared to 2 days in the paediatric population (p=0.003). CONCLUSION: Despite
      cases of infective endocarditis and an incidence of penicillin resistance of 20%,
      mortality directly attributable to VS infection in immunocompetent adults and
      children was rare.

PMID- 18068807
TI  - Selective 5-HT6 receptor ligands: progress in the development of a novel
      pharmacological approach to the treatment of obesity and related metabolic
      disorders.
AB  - The increasing global prevalence of obesity unequivocally demonstrates that
      neither behavioural (diet and exercise) nor pharmacological approaches to this
      health problem are working. In this area of high unmet clinical need, the 5-HT6
      receptor has generated enormous interest amongst academic and pharmaceutical
      industry scientists as a molecular target for the development of a new generation
      of safe and more effective anti-obesity drugs. In this review, we have described
      the major developments that have occurred in the fields of the medicinal
      chemistry and pharmacology of 5-HT6 ligands, with particular emphasis on their
      potential application as novel anti-obesity drugs. The last 5 years have
      witnessed an increasing understanding of the 5-HT6 receptor and its structural
      requirements that has produced an explosion in the number and diversity of novel,
      highly selective 5-HT6 receptor agonists, partial agonists and antagonists that
      have been designed and synthesized. In animal models, 5-HT6 receptor ligands of
      all functional types have been shown to decrease food intake when given acutely
      and chronically, to evoke profound and sustained weight-loss in obese animals,
      and concomitantly to improve a number of cardio-metabolic risk factors.
      Comparator studies in obese animal models, which are highly predictive of
      clinical outcomes, indicate that 5-HT6 ligands may have the potential to be more
      efficacious in the treatment of obesity than the current generation of anti
      obesity drugs.

PMID- 18068808
TI  - Identification of abundant proteins and potential allergens in Culicoides
      nubeculosus salivary glands.
AB  - IgE-mediated type 1 hypersensitivity reactions to the bites of insects are a
      common cause of skin disease in horses. Insect bite hypersensitivity (IBH) is
      most frequently associated with bites of Culicoides spp. and occurs in all parts
      of the world where horses and Culicoides coexist. The main allergens that cause
      IBH are probably some of the abundant proteins in the saliva of Culicoides
      associated with blood feeding. Western blots of Culicoides proteins separated by
      1D gel-electrophoresis detected strong IgE responses in all horses with IBH to
      antigens in protein extracts from wild caught Culicoides, but only weak responses
      to salivary antigens from captive bred C. nubeculosus which may reflect important
      differences among allergens from different species of Culicoides or differences
      between thorax and salivary gland antigens. 2D electrophoresis and mass
      spectrometry were used to identify several of the abundant proteins in the saliva
      of C. nubeculosus. These included maltase, members of the D7 family, and several
      small, basic proteins associated with blood feeding. The most frequently detected
      IgE-binding proteins were in a group of proteins with pI>8.5 and mass 40-50kDa.
      Mass spectrometry identified two of these allergenic proteins as similar to
      hyaluronidase and a heavily glycosylated protein of unknown function that have
      previously been identified in salivary glands of C. sonorensis.

PMID- 18068809
TI  - Coccidia-induced mucogenesis promotes the onset of necrotic enteritis by
      supporting Clostridium perfringens growth.
AB  - This study tested the hypothesis that a host mucogenic response to an intestinal
      coccidial infection promotes the onset of necrotic enteritis (NE). A chick NE
      model was used in which birds were inoculated with Eimeria acervulina and E.
      maxima and subsequently with Clostridium perfringens (EAM/CP). A second group of
      EAM/CP-infected birds was treated with the ionophore narasin (NAR/EAM/CP). These
      groups were compared to birds that were either non-infected (NIF), or infected
      only with E. acervulina and E. maxima (EAM), or C. perfringens (CP). The impact
      of intestinal coccidial infection and anti-coccidial treatment on host immune
      responses and microbial community structure were evaluated with histochemical-,
      cultivation- and molecular-based techniques. Barrier function was compromised in
      EAM/CP-infected birds as indicated by elevated CFUs for anaerobic bacteria and C.
      perfringens in the spleen when compared to NIF controls at day 20, with a
      subsequent increase in intestinal NE lesions and mortality at day 22. These
      results correlate positively with a host inflammatory response as evidenced by
      increased ileal interleukin (IL)-4, IL-10 and IFN-gamma RNA expression.
      Concurrent increases in chicken intestinal mucin RNA expression, and goblet cell
      number and theca size indicate that EAM/CP induced an intestinal mucogenic
      response. Correspondingly, the growth of mucolytic bacteria and C. perfringens as
      well as alpha toxin production was greatest in EAM/CP-infected birds. The
      ionophore narasin, which directly eliminates coccidia, reduced goblet cell theca
      size, IL-10 and IFN-gamma expression, the growth of mucolytic bacteria including
      C. perfringens, coccidial and NE lesions and mortality in birds that were co
      infected with coccidia and C. perfringens. Collectively the data support the
      hypothesis that coccidial infection induces a host mucogenic response providing a
      growth advantage to C. perfringens, the causative agent of NE.

PMID- 18068810
TI  - Lack of detection of circulating skin-specific IgE autoantibodies in dogs with
      moderate or severe atopic dermatitis.
AB  - Human patients with atopic dermatitis (AD) commonly exhibit IgE reactivity to
      cutaneous self-antigens. The presence of serum IgE autoantibodies appears to
      correlate with disease severity, and it is suspected to reflect or contribute to
      tissue damage. The objective of this study was to determine whether IgE
      autoantibodies specific for cutaneous antigens could be detected in the serum of
      dogs with AD. Serum was collected from 19 dogs with untreated moderate to severe
      AD and four specific-pathogen free (SPF) dogs. Indirect immunofluorescence was
      performed using normal canine skin collected at four different locations (concave
      ear, nose, medial thigh and lateral thorax), while Western immunoblotting was
      done using normal canine ear pinna epidermal and dermal extracts and reducing
      conditions. In both methods, IgE was detected using a monoclonal antibody
      specific for heat stable epitopes of canine IgE. At 1:10 dilution, specific IgE
      autoantibodies against cutaneous autoantigens were not detected, with either
      method, in AD and SPF canine sera. Either IgE autoreactivity is not associated
      with moderate to severe AD in dogs, or the methods employed herein were not
      sensitive enough to permit IgE autoantibody detection.

PMID- 18068811
TI  - Thymic output and peripheral T lymphocyte subsets in relapsing--remitting
      multiple sclerosis patients treated or not by IFN-beta.
AB  - We explored the parameters of central and peripheral tolerance in patients with
      stable relapsing-remitting multiple sclerosis, treated or not with IFN-beta. TREC
      positive T cells were lower in patients compared with controls, mainly in CD4+
      subset, compatible with a thymus dysfunction or an expansion of peripheral
      lymphocytes. Compared to controls, the frequency of activated CD4+CD25+ T cells
      was higher in patients without modification of the CD4+CD25(high) T cell
      proportion. The IFN-beta-treatment did not modify the TREC-positive cell
      frequency nor the naive/memory T cell subset percentage but was associated with
      lower blood lymphocyte count and a lower frequency of CD4+CD45RC(high) subset.

PMID- 18068812
TI  - One-step reverse transcriptase polymerase chain reaction for the diagnosis of
      respiratory syncytial virus in children.
AB  - Human respiratory syncytial virus (HRSV) is the main cause of acute lower
      respiratory tract infections in infants and children. Rapid diagnosis is required
      to permit appropriate care and treatment and to avoid unnecessary antibiotic use.
      Reverse transcriptase (RT-PCR) and indirect immunofluorescence assay (IFA)
      methods have been considered important tools for virus detection due to their
      high sensitivity and specificity. In order to maximize use-simplicity and
      minimize the risk of sample cross-contamination inherent in two-step techniques,
      a RT-PCR method using only a single tube to detect HRSV in clinical samples was
      developed. Nasopharyngeal aspirates from 226 patients with acute respiratory
      illness, ranging from infants to 5 years old, were collected at the University
      Hospital of the University of Sao Paulo (HU-USP), and tested using IFA, one-step
      RT-PCR, and semi-nested RT-PCR. One hundred and two (45.1%) samples were positive
      by at least one of the three methods, and 75 (33.2%) were positive by all
      methods: 92 (40.7%) were positive by one-step RT-PCR, 84 (37.2%) by IFA, and 96
      (42.5%) by the semi-nested RT-PCR technique. One-step RT-PCR was shown to be
      fast, sensitive, and specific for RSV diagnosis, without the added inconvenience
      and risk of false positive results associated with semi-nested PCR. The combined
      use of these two methods enhances HRSV detection.

PMID- 18068814
TI  - Management of multidrug-resistant organisms in health care settings, 2006.

PMID- 18068815
TI  - 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious
      Agents in Health Care Settings.

PMID- 18068817
TI  - Fixed-dose combinations for improving medication adherence in assisted living
      environments.

PMID- 18068818
TI  - CMS guidance on the use of paid feeding assistants in nursing homes.

PMID- 18068819
TI  - Fall prevention in assisted living: assessment and strategies.
AB  - Residents in assisted living residences have similar risk factors for falls as do
      community-residing older adults and, as such, can benefit from the research
      findings on falls prevention conducted with that population. Some risk factors
      can be managed, such as, medication side effects, and muscle weakness; others
      such as degenerative neurological changes, cannot. Knowing a resident's falls
      history and conducting a full risk assessment, in combination with appropriate
      interventions, can reduce the probability of a future fall. Exercise appears to
      be the most effective factor in reducing the risk of falls and injuries from
      falls. The fear of falling, whether or not associated with a previous fall, is
      more common among older women and can seriously restrict their quality of life.
      This article describes evidence-based falls risk assessment instruments and
      interventions to reduce falls risk. T'ai chi, for example, can reduce falls risk
      by improving balance. The article describes a standard fall prevention program
      for older adults that can be part of a resident's care or service plan, criteria
      for an occurrence report, quality improvement monitoring, and a formula to
      calculate the residence's monthly falls rate.

PMID- 18068820
TI  - Older adults' functional performance loss and adaptation during chemotherapy.
AB  - The experience of functional performance change in older adults during
      chemotherapy was the focus for this qualitative descriptive study. The 9 female
      and 2 male participants (mean age 70.4, SD 6.6) described their experiences in
      semistructured, tape-recorded interviews. The interview transcripts were analyzed
      making constant comparisons as interviews progressed. Results indicated older
      adults experience losses related to changes in functional performance during
      chemotherapy and make adaptations to those losses. These findings are congruent
      with the literature reporting that individuals modify or replace activities using
      old or new coping methods. Recognizing the impact of functional performance
      changes may facilitate support of older adults throughout chemotherapy. There are
      limitations to the study, primarily related to the sample: 82% were female, all
      were Caucasian, 4 types of cancer were present, but 46% had breast cancer. Future
      studies, especially intervention studies to prevent or address functional
      performance loss, may be warranted.

PMID- 18068821
TI  - Implementation of the resident assessment instrument/minimum data set in the
      nursing home as organization: implications for quality improvement in RN clinical
      assessment.
AB  - The Resident Assessment Instrument/Minimum Data Set (RAI/MDS) used in nursing
      homes (NHs) participating in the Federal Medicare and Medicaid programs is a
      state-of-the-art, computerized clinical assessment instrument. RAI/MDS-derived
      data are essential, used for NH reimbursement, quality measurement, regulatory
      quality monitoring activities, and clinical care planning. Completing or
      coordinating the RAI/MDS, which may be conceived of as implementation, is a
      federally mandated responsibility of the RN involving clinical assessment, a core
      professional competency of any RN. How the RAI/MDS is implemented in each NH
      provides evidence of how each NH as an organization understands both the RAI/MDS
      process and its organizational level responsibility for promotion of RN
      competence in clinical assessment. Research literature related to RAI/MDS
      development, testing, and accuracy is used to identify what is known about
      organizational level implementation of the RAI/MDS. Evidence-based suggestions to
      enhance RN competence in RAI/MDS clinical assessments, given existing
      organizational barriers, are provided.

PMID- 18068822
TI  - Macular degeneration: types, causes, and possible interventions.
AB  - Macular degeneration is the most common cause of blindness in individuals over 50
      years of age. The condition is frequently classified into the categories of
      early, intermediate, and advanced stages. Current interventions concerning
      macular degeneration include a healthy lifestyle, diet, medical intervention,
      surgery, and environmental assistance. Future strategies for individuals with
      macular degeneration will possibly stress gene therapy, retinal transplantation,
      artificial vision, retinal prosthesis, and neuroprotection.

PMID- 18068823
TI  - Social instability blocks functional restitution following motor cortex stroke in
      rats.
AB  - Social interactions have previously been shown to influence stroke outcome. In
      the current experiment we investigated the effects of a changing social
      environment on anatomical and behavioral recovery following motor cortex stroke
      in rats. Adult rats were trained on the Whishaw single pellet reaching task prior
      to receiving a devascularizing stroke lesion of the motor cortex. During the post
      stroke testing period half of the rats were exposed to a form of social
      experience that has previously been shown to stimulate synaptic plasticity in
      frontal cortex circuitry, whereas the remaining rats were housed in pairs, in
      standard cages. At the end of the experiment the brains were processed for Golgi
      Cox staining and dendritic length was measured in layer V of the intact forelimb
      motor area, layer III of Zilles' area Cg3 and layer II/III of Zilles' area AID.
      Social experience was found to completely block the normal spontaneous
      behavioural restitution in the lesion animals. Anatomically, whereas social
      experience selectively increased dendritic length in AID in rats that had not
      undergone behavioral training or the stroke procedure, this was not seen in the
      lesion animals, as the lesion alone produced an increase in dendritic length in
      both AID and Cg3. The findings are discussed in terms of the role of social
      experiences, including stress, on spontaneous plasticity that occurs following
      unilateral motor cortex stroke, and the effectiveness of inducing synaptic
      plasticity to promote behavioural recovery.

PMID- 18068824
TI  - Dopamine tone increases similarly during predictable and unpredictable
      administration of rewarding brain stimulation at short inter-train intervals.
AB  - Unpredicted rewards, but not predicted ones, trigger strong phasic changes in the
      firing rates of midbrain dopamine (DA). In contrast, neurochemical measurements
      of DA tone have failed to reveal an influence of reward predictability. However,
      the subjects of the neurochemical experiments were asked to predict reward onset
      over longer intervals (12s, on average) than the subjects of the
      electrophysiological studies (typically, 2s). Thus, the contrasting effects of
      reward predictability could reflect the difference in the duration of the
      interval separating the predictor from the reward rather than a difference in the
      influence of reward predictability on phasic and tonic DA signaling. This
      hypothesis was tested in rats receiving trains of rewarding electrical brain
      stimulation with either a predictable or unpredictable onset. The mean inter
      train interval was 1.5s, a value close to the 2-s CS-US interval that has been
      used in electrophysiological studies demonstrating the dependence of phasic DA
      responses on reward predictability. Despite the shortened inter-train interval,
      the time courses of the observed stimulation-induced elevations in DA levels were
      very similar, regardless of whether train onset was predictable. This finding is
      consistent with the idea that tonic DA signaling is insensitive to the
      predictability of rewards.

PMID- 18068826
TI  - Mechanisms of and defense against acute ammonia toxicity in the aquatic Chinese
      soft-shelled turtle, Pelodiscus sinensis.
AB  - The objective of this study was to elucidate the mechanisms of acute ammonia
      toxicity in the aquatic Chinese soft-shelled turtle, Pelodiscus sinensis, and to
      examine how this turtle defended against a sublethal dose of NH(4)Cl injected
      into its peritoneal cavity. The ammonia and glutamine contents in the brains of
      turtles that succumbed within 3h to an intraperitoneal injection with a lethal
      dose (12.5 micromolg(-1) turtle) of NH(4)Cl were 21 and 4.4 micromolg(-1),
      respectively. Since the brain glutamine content increased to 8 micromolg(-1) at
      hour 6 and recovered thereafter in turtles injected with a sub-lethal dose of
      NH(4)Cl (7.5 micromolg(-1) turtle), it can be concluded that increased glutamine
      synthesis and accumulation was not the major cause of acute ammonia toxicity in
      P. sinensis. Indeed, the administration of l-methionine S-sulfoximine (MSO; 82
      microgg(-1) turtle), a glutamine synthetase (GS) inhibitor, prior to the
      injection of a lethal dose of NH(4)Cl had no significant effect on the mortality
      rate. Although the prior administration of MSO led to an extension of the time to
      death, it was apparently a result of its effects on glutamate dehydrogenase and
      glutamate formation, instead of glutamine synthesis and accumulation, in the
      brain. By contrast, a prior injection with MK801 (1.6 microgg(-1) turtle), a NMDA
      receptor antagonist, reduced the 24h mortality of turtles injected with a lethal
      dose of NH(4)Cl by 50%. Thus, acute ammonia toxicity in P. sinensis was probably
      a result of glutamate dysfunction and the activation of NMDA receptors. NMDA
      receptor activation could also be exacerbated through membrane depolarization
      caused by the extraordinarily high level of ammonia (21 micromolg(-1) brain) in
      the brain of turtles that succumbed to a lethal dose of NH(4)Cl. One hour after
      the injection with a sub-lethal dose of NH(4)Cl, the brain of P. sinensis
      exhibited an extraordinarily high tolerance of ammonia (16 micromolg(-1) brain).
      The transient nature of ammonia accumulation indicates that P. sinensis could
      ameliorate ammonia toxicity through the suppression of endogenous ammonia
      production and/or the excretion of exogenous ammonia. Despite being ureogenic and
      ureotelic, only a small fraction of the exogenous ammonia was detoxified to urea.
      A major portion of ammonia was excreted unchanged, resulting in an apparent
      ammonotely in the experimental turtles. Since there were increases in total
      essential free amino acid contents in the brain, liver and muscle, it can be
      deduced that a suppression of amino acid catabolism had occurred, reducing the
      production of endogenous ammonia and hence alleviating the possibility of ammonia
      intoxication.

PMID- 18068825
TI  - Development of a mouse test for repetitive, restricted behaviors: relevance to
      autism.
AB  - Repetitive behavior, a core symptom of autism, encompasses stereotyped responses,
      restricted interests, and resistance to change. These studies investigated
      whether different components of the repetitive behavior domain could be modeled
      in the exploratory hole-board task in mice. Four inbred mouse strains, C57BL/6J,
      BALB/cByJ, BTBR T+tf/J, and FVB/NJ, and mice with reduced expression of Grin1,
      leading to NMDA receptor hypofunction (NR1neo/neo mice), were tested for
      exploration and preference for olfactory stimuli in an activity chamber with a 16
      hole floor-board. Reduced exploration and high preference for holes located in
      the corners of the chamber were observed in BALB/cByJ and BTBR T+tf/J mice. All
      inbred strains had initial high preference for a familiar olfactory stimulus
      (clean cage bedding). BTBR T+tf/J was the only strain that did not demonstrate a
      shift in hole preference towards an appetitive olfactory stimulus (cereal or a
      chocolate chip), following home cage exposure to the food. The NR1neo/neo mice
      showed lower hole selectivity and aberrant olfactory stimulus preference, in
      comparison to wildtype controls. The results indicate that NR1neo/neo mice have
      repetitive nose poke responses that are less modified by environmental
      contingencies than responses in wildtype mice. 25-30% of NMDA receptor
      hypomorphic mice also show self-injurious responses. Findings from the olfactory
      studies suggest that resistance to change and restricted interests might be
      modeled in mice by a failure to alter patterns of hole preference following
      familiarization with an appetitive stimulus, and by high preference persistently
      demonstrated for one particular olfactory stimulus. Further work is required to
      determine the characteristics of optimal mouse social stimuli in the olfactory
      hole-board test.

PMID- 18068827
TI  - Congenicity and genetic polymorphism in cloned lines derived from a single
      isolate of a rodent malaria parasite.
AB  - Many of the most commonly studied lines of the rodent malaria parasite Plasmodium
      yoelii yoelii originated from a single parasite isolate designated 17X. Amongst
      these lines, however, are parasites that exhibit variation in genotype and
      phenotype (e.g. growth rate). We describe here the results of a comparative
      genetic analysis between cloned lines of 17X that differ in growth rate, using
      nucleotide sequences of specific genes and patterns of genome-wide amplified
      fragment length polymorphism (AFLP). Our findings indicate that the original
      stock of 17X comprises two unrelated genotypes. Genotype-1 is represented by
      parasites with a slow growth phenotype (e.g. 17X (NIMR)) and a fast growth
      phenotype (e.g. 17XYM). Within this genotype, there are also genomic differences
      manifest as a small number of AFLP bands that differentiate the fast- and slow
      growing lines from each other. The other genotype, genotype-2, is represented
      only by parasites with a slow growth phenotype (e.g. 17XA).

PMID- 18068830
TI  - Changing axis deviation with changing bundle branch block and new-onset of atrial
      fibrillation during acute myocardial infarction.
AB  - Paroxysmal atrial fibrillation is considered a frequent complication of acute
      myocardial infarction.It has been rarely reported alternating right and left
      bundle branch block associated with atrial fibrillation. It has also been rarely
      reported changing axis deviation with left bundle branch block also during atrial
      fibrillation and acute myocardial infarction. We present a case of changing axis
      deviation with changing bundle branch block and new-onset of atrial fibrillation
      in a 96-year-old Italian man with acute myocardial infarction.

PMID- 18068828
TI  - Frailty is associated with postoperative complications in older adults with
      medical problems.
AB  - We sought to test whether frailty may be predictive of operative risk in older
      adults with medical problems. One hundred and twenty-five patients at least 70
      years of age had a previously developed frailty screen, the Edmonton Frail Scale
      (EFS), administered at a pre-surgical clinic, prior to elective non-cardiac
      surgery. A blinded chart audit assessed for postoperative medical complications,
      length of stay and inability to be discharged home. The mean age of patients was
      77 (range 70-92) and most (82%) underwent orthopedic procedures. Increasing
      frailty was associated with postoperative complications (p=0.02), increased
      length of hospitalization (p=0.004) and inability to be discharged home (p=0.01),
      independent of age. EFS scores of 3 or less were associated with a lower risk of
      having a complication (age-adjusted OR 0.27, 95% CI 0.09-0.80, likelihood ratio
      of 0.33) and a higher chance (80%) of being discharged home (p<0.02). EFS scores
      exceeding 7 were associated with increased complications (OR 5.02, 95% CI 1.55
      16.25, likelihood ratio of 3.9) and a lower chance of being discharged home (40%,
      p<0.02). This study suggests that a frailty screen can refine risk estimates of
      postoperative complications in older adults undergoing elective non-cardiac
      surgery.

PMID- 18068829
TI  - A randomized controlled trial of Turkish folklore dance on the physical
      performance, balance, depression and quality of life in older women.
AB  - The present study has been carried out to investigate the effects of group-based
      Turkish folkloric dances on physical performance, balance, depression and quality
      of life (QoL) in 40 healthy adult elderly females over the age of 65 years.
      Subjects were randomly allocated into Group 1 (folkloric dance-based exercise)
      and Group 2 (control). A 8-week dance-based exercise program was performed.
      Outcome measures included a 20-m walk test, a 6-min walk test, stair climbing and
      chair rise time, Berg balance scale (BBS), the Medical Outcomes Study (MOS) 36
      item short form health survey (SF-36), and geriatric depression scale (GDS)
      questionnaires. In Group 1 statistically significant improvements were found in
      most of the physical performance tests, BBS and some SF-36 subscales after the
      exercise (p<0.05). In the Group 2 there was no clinically significant change in
      the variables. Comparing the groups, significant improvements in favor of Group 1
      have emerged in most of the functional performance tests, in some of the SF-36
      subscales and BBS score (p<0.05). We achieved improvements in physical
      performance, balance and QoL in elderly females. Application of folkloric dance
      specific to countries as an exercise program for elderly people may be helpful.

PMID- 18068831
TI  - Pulmonary emboli originating from infective endocarditis of the mitral valve
      migrating through an atrial septal defect.
AB  - We report a case of infective endocarditis of the mitral valve, which was
      accompanied by pulmonary emboli traveling through an atrial septal defect. An 18
      year-old male was admitted to our hospital due to a fever, polyarthritis and
      subcutaneous hemorrhage. Transthoracic echocardiography revealed a mobile mass
      and possible vegetation lodged in the mitral valve and a secundum-type atrial
      septal defect. Computed tomography revealed a hepatic, splenic and renal embolic
      infarction. During antibiotic therapy, he felt a sudden right flank pain. Follow
      up computed tomography revealed a pulmonary embolic infarction that drifted
      through an atrial septal defect. This association is the first report, of
      pulmonary emboli which migrated through an atrial septal defect from the mitral
      valve.

PMID- 18068832
TI  - Rarely seen cardiotoxicity of lithium overdose: complete heart block.
AB  - INTRODUCTION: Serious cardiac toxicity due to lithium toxicity is uncommon and
      generally only occurs in individuals with underlying heart disease. Cardiac
      impairment may result in dysrhythmias, including sinus bradycardia, sinoatrial
      block, and first-degree atrioventricular block. This paper describes a patient
      with complete AV block in the course of chronic lithium treatment. CASE REPORT:
      Fifty-seven year-old female was brought into the emergency department (ED) due to
      altered mental status and malaise by ambulance from hospice. She had
      hypertension, type-II diabetes mellitus, and depression. The caregivers told that
      she had been fine yesterday, had taken regular medications (lysinopril,
      furosemid, acetyl salicylic acid, oral antidiabetic tablets and lithium (300 mg
      tb/day)). Her vital signs were; blood pressure: 70/45 mmHg, pulse: 37 bpm,
      respiratory rate: 22 bpm, and oxygen saturation 86%. She was confused and
      unresponsive to verbal stimulation. Her EKG revealed total atrioventricular
      block. Initial biochemical results were unremarkable except for a lithium level
      of 2.2 mmol/l (therapeutic range 0.5-0.8 mmol/l) and an increased creatinine of
      2.11 mg/dl. A transvenous pacing electrode was introduced into the right
      ventricle, which allowed rapid restoration of haemodynamic and neurological
      status. Her neurologic examination was completely normal in the follow-up period
      and she was discharged without sequelae. CONCLUSION: In conclusion, emergency
      physicians should bear in mind that complete AV block can ensue in the course of
      lithium toxicity and it is an entity that should be included in the differential
      diagnosis.

PMID- 18068833
TI  - Can sleep apnea explain adverse outcome of chronic kidney disease in heart
      failure?

PMID- 18068834
TI  - A new method for assessment of plaque vulnerability based on vasa vasorum
      imaging, by using contrast-enhanced intravascular ultrasound and differential
      image analysis.
AB  - BACKGROUND: Increased neovascularization in vasa vasorum and atherosclerotic
      plaques has recently been identified as a common feature of inflammation and
      plaque vulnerability. Microbubble contrast agents, which have been used for
      intravascular imaging, can be used to trace neovascularization. The aim of the
      study was to detect and evaluate the density of vasa vasorum in non-culprit
      coronary atherosclerotic plaques of patients with acute coronary syndrome.
      METHODS: We have studied intravascular ultrasound (IVUS) signals before, during,
      and after intracoronary injection of microbubbles, proximal to non-culprit
      atherosclerotic plaques in 16 patients with acute coronary syndrome. Analyses
      were accomplished using a computational algorithm for the detection of contrast
      perfusion in such contrast-enhanced sequences. Perfusion density was evaluated by
      the mean enhancement in the region of interest provided by this difference
      imaging technique. RESULTS: Qualitative and quantitative analysis of the pre- and
      post-injection images showed a significant enhancement in the grey-scale
      intensity of intima-media and adventitia after injection (intima-media: from
      6.0+/-2.5 to 7.9+/-3.3%, p=0.006 and adventitia: from 7.1+/-2.2 to 7.6+/-2.5%,
      p=0.035). CONCLUSIONS: Contrast-enhanced intravascular imaging is a novel, yet
      clinically available, technique that has the potential to enhance IVUS-based
      characterization of atherosclerotic plaques. The technique introduces a new
      perspective to the detection of vulnerable plaques and warrants further
      investigations.

PMID- 18068835
TI  - Elevated heart rate and atherosclerosis: an overview of the pathogenetic
      mechanisms.
AB  - Several epidemiological studies have reported that an elevated heart rate is
      associated with coronary atherosclerosis independently of other risk factors. In
      this review we explore the pathophysiologic mechanisms involved in the pro
      atherosclerotic effect of elevated heart rate, apart from its association with
      sympathetic tone. An elevated heart rate enhances the magnitude and frequency of
      the tensile stress imposed on the arterial wall and prolongs the exposure of
      coronary endothelium to the systolic low and oscillatory shear stress. Moreover,
      increased heart rate intensifies the pulsatile motion of the heart and,
      therefore, the frequency of the periodically changing geometry of the coronary
      arteries, thereby affecting the local hemodynamic environment. All these
      processes induce structural and functional changes of the endothelial cells,
      which are accumulated over the time in atherosclerosis-prone regions promoting
      atherosclerosis. Heart rate should be considered in every patient with coronary
      heart disease, especially since it is an easily measurable and reproducible
      parameter. Slowing the heart rate could potentially decrease the progression of
      atherosclerosis by reducing the local pro-atherosclerotic vascular environment.
      This effect may be involved in any beneficial role of heart rate lowering agents
      in preventing coronary heart disease.

PMID- 18068837
TI  - Development of severe and persistent hypoxemia seven months after orthotopic
      heart transplantation.
AB  - We report the case of a 57-year-old man who underwent orthotopic heart
      transplantation because of prior myocardial infarction and cardiogenic shock. The
      patient developed refractory hypoxemia 7 months after transplantation, secondary
      to a right to left shunt across a patent foramen ovale related to severe
      tricuspid regurgitation resulting from repeated control biopsies. Percutaneous
      closure of the foramen ovale was performed.

PMID- 18068838
TI  - A reliable transformation method and heterologous expression of beta
      glucuronidase in Lentinula edodes.
AB  - A simple and reliable mushroom transformation procedure based on electroporation
      of basidiospores or mycelial fragments was developed. This method eliminated the
      problem of protoplast preparation, the transformation efficiency were 30-150
      transformants per mug DNA and the hygromycin resistant marker gene and gus were
      expressed in Lentinula edodes successfully. No false positive antibiotic
      resistant cultures were detected by PCR amplification and the beta-glucuronidase
      (GUS) expression was maintained stable during mitotic cell division without
      selection pressure for more than 6 months. Southern analysis of transformants
      indicated the integration of gene might occur by non-homologous recombination.
      Using the glyceraldehyde-3-phosphate dehydrogenase (gpd) promoter with the first
      intron of gpd gene, the average GUS activity in L. edodes reached 144.6+/-3.9 U
      mg(-1) soluble protein, while only 30.1+/-0.7 U mg(-1) soluble protein was
      detected for those without the intron. The percentage of GUS in total soluble
      protein was 5.67 x 10(-4) (0.06%) for the transformant with the highest GUS
      activity. This rapid and convenient electroporation procedure offers a new
      approach for the genetic manipulation and tool to tag genes of important edible
      mushroom species.

PMID- 18068839
TI  - Exploiting the combined effects of high pressure and moderate heat with nisin on
      inactivation of Clostridium botulinum spores.
AB  - In the present work, we studied the combined effects of pressure (300.0-700.0
      MPa), temperature (30-70 degrees C) and the presence of nisin (0-333 IU/ml) on
      the inactivation of Clostridium botulinum 33A spores at various pressure holding
      times (7.5-17.5 min). Moreover, response surface methodology (RSM) was employed
      and a quadratic equation for HPP and nisin-induced inactivation was built with
      RSM. By analyzing the response surface plots and their corresponding contour
      plots as well as solving the quadratic equation, the experimental values were
      shown to be significantly in good agreement with predicted values because the
      adjusted determination coefficient (R(Adj)(2)) was 0.9261 and the level of
      significance was P<0.0001. The optimum process parameters for a six-log cycle
      reduction of C. botulinum spores were obtained as: pressure, 545.0 MPa;
      temperature, 51 degrees C; pressure holding time, 13.3 min; and nisin
      concentration, 129 IU/ml. The adequacy of the model equation for predicting the
      optimum response values was verified effectively for 10 test points. Compared to
      conventional high pressure processing (HPP) techniques, the main process
      advantages of HPP-nisin combination sterilization in the UHT milk are, lower
      pressure, natural preservative (nisin), and temperature in a shorter treatment
      time.

PMID- 18068841
TI  - Tissue segmentation in Monte Carlo treatment planning: a simulation study using
      dual-energy CT images.
AB  - PURPOSE: Tissue segmentation is an important step in Monte Carlo (MC) dose
      calculation and is often done uncritically. A new approach to tissue segmentation
      using dual-energy CT images is studied in this work. MATERIALS AND METHODS: A
      simple MC model of a CT scanner was built and CT images of phantoms with ten
      tissue-equivalent cylinders were simulated using soft and hard X-ray spectra. The
      Z and rho(e) of the cylinders were extracted using a formalism based on a
      parameterization of the linear attenuation coefficient. RESULTS: It was shown
      that in order to extract Z and rho(e) with a reasonable accuracy, hard X-ray
      beams have to be used for scanning. When an additional filtration of 9 mm of
      aluminium in the CT X-ray beam is used, beam hardening in high density materials
      is suppressed and the mean errors of the extraction of Z and rho(e) for 10 tissue
      equivalent materials in a small tissue-equivalent phantom are 3.7% and 3.1%,
      respectively. CONCLUSIONS: MC simulations were used to show that the extraction
      of Z and rho(e) for a number of tissue-equivalent materials using dual-energy CT
      images is possible which improves tissue segmentation for Monte Carlo dose
      calculations, as demonstrated with a 250 kVp photon beam dose calculation.

PMID- 18068843
TI  - PCR detection of Staphylococcal enterotoxins (SEs) N, O, P, Q, R, U, and survey
      of SE types in Staphylococcus aureus isolates from food-poisoning cases in
      Taiwan.
AB  - Staphylococcal enterotoxins (SEs) are superantigenic toxins. They are five major
      classical types, i.e., SEA, SEB, SEC, SED, SEE, and new SEs or SE-like
      superantigens, such as SEG to SEU. Only the staphylococcal superantigens (SAgs)
      that induce emesis following oral administration in a monkey model are designated
      as SEs while other related toxins are called SE-like (SEl) superantigens. To
      survey the enterotoxin genotypes for S. aureus strains isolated from food
      poisoning cases in Taiwan, we developed PCR primers specific for SEN, SEO, SEP,
      SEQ, SER, and SEU genes. The complete SE sequences and their expression potential
      for strains positive to sen, seo, sep, seq, ser, and seu specific primers were
      also determined. These strains were used as reference strains. With the PCR
      primers specific for all SEs or SAgs, including toxic shock syndrome toxin I
      (TSST-1), we assayed the genotypes of 147 S. aureus strains isolated from
      patients associated with staphylococcal food-poisoning outbreaks occurred during
      2001-2003. For these 147 strains, 135 (91.8%) were found positive for one or more
      SE or SAg genes. For classical enterotoxin and TSST-1 types, the major one was
      tsst-1 (59.1%) following by sea (29.2%), seb (19.7%), sec (6.8%), and sed (2.0%).
      For new SE and SAg types, the major one was sei (29.9%) and sep (27.9%) followed
      by, sek (16.3%), seo (14.3%), seu (14.2%), sem (11.6%), sen (10.9%), seq (10.9%),
      seh (8.2%), sel (6.8%), and ser (5.4%) etc. This report reveals the whole SE and
      SAg genotypes for S. aureus strains isolated from staphylococcal food-poisoning
      cases in Taiwan.

PMID- 18068842
TI  - Effect of fermentation temperature and culture media on the yeast lipid
      composition and wine volatile compounds.
AB  - The temperature of a wine fermentation strongly affects lipid metabolism and
      thus, aromatic profiles. Most of the metabolic studies are done in well
      controlled laboratory conditions, yet wine is produced in less-reproducible
      industrial conditions. The aim of this study is to analyse the effect of
      fermentation temperature (13 degrees C and 25 degrees C) and culture media
      (synthetic media and grape must) on yeast lipid composition and volatile
      compounds in wine. Our results show that yeast viability was better at 13 degrees
      C than at 25 degrees C whichever growth medium is used, but that the complexity
      of the grape must enabled cells to reach higher viable population size. Viability
      was also related to the incorporation of linoleic acid and beta-sitosterol, which
      were present in the grape must. A lower temperature modified the cellular lipid
      composition of yeast, increasing the degree of unsaturation at the beginning of
      fermentation and decreasing the chain length as fermentation progressed. We also
      found that medium-chain fatty acids, mainly dodecanoic acid, were present in the
      cell phospholipids. Wines produced from grape must were more aromatic and had a
      lower volatile acidity content than those derived from a synthetic medium.
      Fermentations that were performed at the lower temperature also emphasized this
      feature.

PMID- 18068844
TI  - Broad distribution of enterotoxin genes (hblCDA, nheABC, cytK, and entFM) among
      Bacillus thuringiensis and Bacillus cereus as shown by novel primers.
AB  - Eight new pairs of PCR primers were designed and efficiently detect eight toxin
      genes (hblC, hblD, hblA, nheA, nheB, nheC, cytK, and entFM) in 411 B. cereus
      strains (121 food- and 290 soil isolates) and 205 B. thuringiensis strains (43
      serovars, 10 food- and 152 soil isolates). According to the presence of these
      eight toxin genes, they were divided into four groups among the total 616
      isolates. In Group I, all eight genes occurred simultaneously in 403 (65.42%)
      isolates, while Group II (134 isolates or 21.75%) and Group III (46 isolates or
      7.47%) were devoid of hblCDA and cytK, respectively. In Group IV, there were
      thirty-three isolates which lacked both hblCDA and cytK. The presence of hblCDA
      in B. thuringiensis strains (86.80%) was significantly higher (P<0.05) than in B.
      cereus strains (66.18%) whereas no significant difference in nheABC, cytK and
      entFM occurrence was detected between both bacterial groups. Both nheABC and
      entFM genes were found in all B. cereus and B. thuringiensis strains (616 strains
      in total), while the cytK gene could be detected in 365 (88.80%) of the B. cereus
      and 172 (83.90%) of the B. thuringiensis strains. None of the 616 tested strains
      showed the presence of only a single or two genes in either the hbl or nhe
      operons. The eight primer pairs designed for this multiplex PCR allowed rapid
      detection of eight toxin genes from boiled cells with high sensitivity, gave 100%
      reproducibility, and did not cross-react to 32 other bacterial strains.

PMID- 18068845
TI  - Filamentous fungi producing ochratoxin a during cocoa processing in Cameroon.
AB  - Ochratoxin A (OTA) is the main mycotoxin occurring in cocoa. A study was
      conducted in Cameroon to assess how filamentous fungi and toxigenesis were
      affected by the type of cocoa post-harvest treatment (boxes or heaps). The
      filamentous fungi isolated were almost identical when fermentation was carried
      out in boxes or heaps, with the presence of abundant black Aspergillus
      filamentous fungi: A. niger and A. carbonarius. Filamentous fungi were more
      abundant at the end of the harvesting season. Factors affecting bean integrity
      (poor handling, deferred processing) resulted in a qualitative and quantitative
      increase in contamination, when the total number of filamentous fungi could reach
      a maximum value of 5.5+/-1.4x10(7) CFU g(-1) and black Aspergilli a maximum value
      of 1.42+/-2.2x10(7) CFU g(-1). A toxigenesis study showed that Aspergillus
      carbonarius was the main OTA-producing strain isolated. Its maximum production
      could reach 2.77 microg g(-1) on rice medium. Aspergillus niger strains did not
      always produce OTA and their toxigenesis was much lower. Fermented dried cocoa
      from poor quality pods was the most contaminated by OTA: up to 48 ng g(-1).

PMID- 18068846
TI  - Growth control of Listeria innocua 2030c on vacuum-packaged cold-smoked salmon by
      lactic acid bacteria.
AB  - Five bacteriocin-producing lactic acid bacteria (LAB): Enterococcus faecium ET05,
      Lactobacillus curvatus ET06, L. curvatus ET30, L. deldrueckii ET32 and
      Pediococcus acidilactici ET34, selected by their capacity for growth and
      producing inhibition in vitro at high salt-on-water content, low temperature and
      anaerobic atmosphere, conditions simulating cold-smoked fish, were inoculated
      onto salmon fillets, in co-culture with Listeria innocua 2030c, and cold-smoked
      processed (dry salted for 6 h; drying for 6 h; smoke for 2 h). The finished
      product was then packed under vacuum and stored at 5 degrees C. Enumeration of
      LAB and L. innocua was performed during storage. Results showed that strain E.
      faecium ET05 was the best biopreservative candidate for controlling L. innocua
      growth in vacuum-packaged cold-smoked salmon (CSS) processed under the
      salting/drying/smoking parameters referred above. L. curvatus ET30 and L.
      delbrueckii ET32 also showed a good biopreservation potential for CSS although
      they were less effective than the former. L. curvatus ET06 and P. acidilactici
      ET34 showed a bacteriostatic mode of action against the target bacteria in vitro
      as well as when inoculated into the salmon fillets. This study describes a
      potential application of five different LAB in the biopreservation of Listeria in
      CSS.

PMID- 18068847
TI  - An analytical method for determining relative specificities for sequential
      reactions catalyzed by the same enzyme: application to the hydrolysis of
      triacylglycerols by lipases.
AB  - We propose a model for the sequential hydrolysis of ester bonds of
      triacylglycerols by lipases and use it as the basis for an analytical method for
      determining the relative specificity of the lipase for the various substrates
      with which it can react, when the substrates occur simultaneously in a single
      reaction system. We then apply the method to our own data and literature data
      involving the hydrolysis of triacylglycerols by lipases. Our model is able to fit
      well to most of the reaction profiles, enabling the estimation of relative
      specificities. We discuss the limitations and potential applications of our
      method.

PMID- 18068848
TI  - DNA condensation by poly-L-lysine at the single molecule level: role of DNA
      concentration and polymer length.
AB  - Cationic poly(aminoacids) like poly-L-lysine (PLL) are known to be efficient in
      condensing plasmid DNA into compact nanostructures and have been used for in
      vitro and in vivo delivery of therapeutic DNA. Our study emphasizes on
      understanding the molecular mechanism of PLL-induced DNA condensation and the
      factors controlling it by visualization using Atomic Force Microscopy (AFM).
      Molecular morphologies were observed using AFM at increasing charge ratios as PLL
      interacts with DNA (Z+/Z- varied between 0.1 and 1.5) using PLL of different
      lengths (average 19, 41 and 120 residues) at varying DNA concentrations (3-20
      ng/microl). The nature of the structures (rods, toroids, aggregates, flower-like
      structures, and nanoparticles), the condensation pathways and condensation
      efficiencies are strongly dependent on the charge ratios, the length of PLL and
      DNA concentration. DNA condensation is monomolecular at low DNA concentrations
      and involves multimolecular condensation also at higher DNA concentration. PLL of
      the smallest length chosen here was found be the most efficient in condensing DNA
      at low DNA concentrations. Understanding the role of these factors could be
      helpful in rationalizing and predicting efficacy of intracellular delivery of DNA
      nanocarriers under different conditions and hence provide important inputs for
      design of novel gene delivery vectors.

PMID- 18068849
TI  - Targeted delivery of anti-CD19 liposomal doxorubicin in B-cell lymphoma: a
      comparison of whole monoclonal antibody, Fab' fragments and single chain Fv.
AB  - As part of an ongoing effort to develop a clinically acceptable doxorubicin
      formulation, targeted against B-cell malignancies, this study compared long
      circulating (Stealth) immunoliposomes (SIL) that were targeted against the B-cell
      antigen CD19, via a whole HD37 monoclonal antibody (HD37 mAb), versus its Fab'
      fragment (HD37 Fab') or an HD37-c-myc-Cys-His5 single chain Fv fragment (scFv,
      HD37-CCH) directed against the same epitope. Compared to untargeted liposomes
      (SL), SIL showed increased binding in vitro to CD19-expressing Raji cells and,
      when loaded with doxorubicin (SIL-DXR), increased cytotoxicity against Raji
      (CD19(+)), but not Molt4 (CD19(-)) cells. Pharmacokinetics and biodistribution
      studies using dual-labeled liposomes (lipid and drug) in naive and Raji-bearing
      mice showed that SIL-DXR targeted via HD37 Fab' exhibited the same long
      circulation half-life as SL-DXR. SIL-DXR targeted via HD37-CCH was cleared faster
      than SL-DXR due to increased liver uptake, which was related to the poly-His
      and/or the c-myc tags in the scFv construct. SIL-DXR targeted via HD37 mAb was
      cleared rapidly from circulation due to Fc-mediated uptake in the liver and
      spleen. All three formulations of SIL-DXR extended the mean survival time of Raji
      bearing mice compared to SL-DXR or free DXR. SIL-DXR targeted via HD37 Fab',
      which had the longest circulation half-life, appeared to be slightly more
      effective in prolonging survival times than SIL-DXR targeted via either HD37-CCH
      or HD37 mAb.

PMID- 18068850
TI  - Demonstration of cooperative contribution of MET- and EGFR-mediated STAT3
      phosphorylation to liver regeneration by exogenous suppressor of cytokine
      signalings.
AB  - BACKGROUND/AIMS: As conditional knockout mice for stat3 are impaired in liver
      regeneration after partial hepatectomy while those for gp130 have defects in
      early STAT3 phosphorylation but have normal DNA synthesis, late STAT3
      phosphorylation induced independently of gp130 seems to be essential for liver
      regeneration. Since HGF and EGF can activate STAT3 via gp130-independent MET and
      EGFR, respectively, we assumed that these factors account for STAT3-dependent
      liver regeneration. Here, we investigated this hypothesis by introducing
      suppressor of cytokine signaling (SOCS)-1 and SOCS3, potent negative regulators
      of STAT3 signaling, selectively in hepatocytes. METHODS: We generated recombinant
      adenoviruses expressing socs1 and socs3. RESULTS: Hepatocytes infected with socs1
      virus lacked STAT3 phosphorylation in response to IL-6 and HGF, while cells
      infected with socs3-virus lacked the response to all of IL-6, HGF and EGF,
      indicating that those SOCS proteins differently regulate EGFR signaling. Mice
      infected with socs3-virus exhibited severe and persistent impairment while those
      with socs1-virus showed only delayed regeneration, indicating requirement of both
      MET and EGFR signalings. CONCLUSIONS: These results clearly demonstrated that MET
      and EGFR-mediated STAT3 signalings cooperatively contribute to liver
      regeneration and could provide new insights into tissue homeostasis.

PMID- 18068851
TI  - A portable device for intensive care brain function monitoring with event-related
      potentials.
AB  - Monitoring level of consciousness or depth of sedation is essential in modern
      intensive care units and emergency rooms. Current methods are based on
      spontaneous EEG providing only indirect information on the reactivity of the
      brain. Measurement of auditory event-related potentials (ERPs) has been shown to
      have additional potential for evaluation of the level of consciousness.
      Unfortunately, compact and easy-to-use devices are not commercially available. In
      this study a portable battery-powered device for clinical auditory ERP
      measurements was designed, constructed and validated. The device consists of a
      five-channel data logger and a 16-bit stereo audio stimulator. The signals are
      digitized with a 22-bit sigma-delta analogue-to-digital converter and stored to a
      PC Card hard disk. Prior to the in vivo application, the device was validated
      with extensive technical tests. Importantly, the RMS noise amplitude of the EEG
      channels was found to be less than 1 mivroV and the delivered auditory stimulus
      intensity corresponded accurately the settings (mean difference 0.2+/-0.5 dB). In
      addition to technical tests the device was successfully validated in vivo. To
      summarize, a novel portable instrument for measurement of auditory event-related
      potentials in intensive care environment is introduced.

PMID- 18068852
TI  - Polymorphisms in excision repair cross-complementing group 4 (ERCC4) and
      susceptibility to primary lung cancer in a Chinese Han population.
AB  - ERCC4/XPF protein plays an important role in the nucleotide excision repair (NER)
      pathway, and deficiencies in the gene encoding it can lead to a repair-deficiency
      syndrome, xeroderma pigmentosum group F (XP-F). Common variants on this gene are
      assumed to be foreboding markers for lung cancer, and 4 selected SNPs in the
      ERCC4 gene were genotyped in a multi-center case-control study involving 1010
      lung cancer patients and 1011 cancer-free controls in a Chinese Han population to
      test the hypothesis. A significant association to decreased risk of lung cancer
      was observed in major allele C of rs3136038 carriers (adjusted OR=0.57, 95%
      CI=0.39-0.84 for CT; adjusted OR=0.75, 95% CI=0.52-1.10 for CC; adjusted OR=0.68,
      95% CI=0.46-0.99 for CT+CC, compared with genotype TT), and additionally,
      referenced with homozygote TT, the heterozygous genotype CT showed a distinct
      protective effect in younger subjects (adjusted OR=0.47, 95% CI=0.26-0.86), in
      males (adjusted OR=0.59, 95% CI=0.37-0.93), in non-smokers (adjusted OR=0.38, 95%
      CI=0.20-0.72), in subjects without family history of cancer (adjusted OR=0.52,
      95% CI=0.34-0.80) and in adenocarcinomas patients (adjusted OR=0.51, 95% CI=0.31
      0.84). Our finding indicated, for the first time, the polymorphism rs3136038 on
      the promotor region of ERCC4 may contribute to the etiology of lung cancer.
      Further functional studies on this locus and/or other genetic variants in highly
      linkage disequilibrium with it are warranted to elucidate the underlying
      molecular mechanisms of the association.

PMID- 18068853
TI  - A phase II study of biweekly paclitaxel (P) and gemcitabine (G), followed by
      maintenance weekly paclitaxel in elderly patients with advanced non-small cell
      lung cancer (NSCLC).
AB  - BACKGROUND: This phase II study was conducted to evaluate the efficacy and safety
      of a novel combination of paclitaxel (P) and gemcitabine (G) in an every 2 weeks
      schedule followed by weekly paclitaxel (P) as first-line treatment in elderly
      patients with locally advanced or metastatic NSCLC. METHODS: Elderly patients (>
      or =65 years of age) with 1997 TNM stage IIIB (pleural effusion)/stage IV NSCLC,
      performance status (PS) of 0-2 and normal organ function were eligible. Therapy
      consisted of P at 150 mg/m(2) and G at 2000 mg/m(2) administered every 2 weeks
      for 3 cycles followed, in progression-free patients, by P at 80 mg/m(2) every
      week for 6 consecutive weeks every 8 weeks for 2 cycles. RESULTS: Fifty-three
      eligible patients were enrolled: M/F 51/2; stage IIIB/IV 8/45; PS 0, 40%, PS 1
      51%, PS 2 9%; median age, 73 years (range 67-82). The overall response rate was
      32% (95% confidence interval [CI]: 19-45). The median overall survival was 7
      months (95% CI: 5-9); the median progression-free survival was 5 months (95% CI:
      3-6); and the 1- and 2-year survivals were 28.3% and 10.1%, respectively. Both
      phases of the treatment protocol were well tolerated. CONCLUSIONS: Biweekly P/G
      followed by weekly P is well tolerated and active as first-line therapy for
      elderly NSCLC patients.

PMID- 18068854
TI  - The role of familiarity on modeling of eating and food consumption in children.
AB  - This study investigates the effects of peer and sibling influence on the cookie
      intake of normal-weight children. A total of 44 children (24 girls and 20 boys)
      aged 5-11 participated in this study. Children played a sorting task while being
      exposed to a large amount of cookies. Children were tested alone or with an
      unfamiliar peer or with a sibling. Results indicated that the social condition
      was related to the participants' energy intake. Children eating with their
      siblings ate more cookies than did children eating with strangers and also
      consumed more cookies than did children eating alone. This pattern of results is
      consistent with previous research in adults indicating that familiarity between
      co-eaters influence how much one choose to eat. Furthermore, the degree of intake
      matching was extremely high among strangers, but low and not statistically
      significant in dyads of siblings. We conclude that matching effect is not
      ubiquitous and that familiarity affects the level of matching of eating in
      children.

PMID- 18068855
TI  - Connective tissue diseases.

PMID- 18068856
TI  - Systemic lupus erythematosus: modern strategies for management: a moving target.
AB  - Rapid advances in understanding the immunopathogenesis of systemic lupus
      erythematosus (SLE) have yielded an unprecedented era of discovery of new targets
      with therapeutic potential. Recent clinical trials have also shed light on the
      optimal utility of several traditional therapies used in our SLE armamentarium.

PMID- 18068858
TI  - Undifferentiated connective tissue diseases (UCTD): a new frontier for
      rheumatology.
AB  - Patients with signs and symptoms suggestive of a systemic autoimmune disease but
      not fulfilling the classification criteria for defined diseases are common in
      clinical practice. Such conditions have been defined as undifferentiated
      connective tissue diseases (UCTDs). Since the 1980s, many studies have analyzed
      different aspects of the UCTDs -- their frequency and epidemiological
      characteristics, the rate of evolution to defined CTD, and their clinical and
      serological characteristics. It is agreed that UCTDs represent around 60% of
      diseases with an undifferentiated onset, that they are systemic autoimmune
      diseases characterized by simplified clinical and serological profiles, and that
      they have a good prognosis. Although many aspects of these conditions have been
      studied and clarified, there is still no agreement on how best to identify UCTD
      patients after the onset of their disease. However, such identification is of
      paramount importance, and further analysis is necessary to improve the
      sensitivity and specificity of the proposed classification criteria.

PMID- 18068857
TI  - Update on Sjogren's syndrome autoimmune epithelitis: from classification to
      increased neoplasias.
AB  - Sjogren's syndrome is a chronic inflammatory process that primarily involves the
      exocrine glands. Its clinical manifestations range from autoimmune exocrinopathy
      to extraglandular (systemic) involvement affecting the lungs, kidneys, blood
      vessels, and muscles; it can occur alone (primary Sjogren's syndrome) or in
      association with other autoimmune diseases (secondary Sjogren's syndrome). In
      recent years, clinical and laboratory observations have highlighted the central
      role of the epithelial cell and it has been suggested that the etiological name
      of the disease should be 'autoimmune epithelitis'. The extraglandular
      manifestations of the disease are divided in two groups: (1) lung, kidney
      (interstitial nephritis), and liver involvement as a result of lymphocytic
      invasion in epithelial tissues; and (2) skin vasculitis, peripheral neuropathy,
      and glomerulonephritis, with low C4 levels, which is the result of immune complex
      disease, are associated with increased morbidity and high risk for lymphoma. The
      diagnosis of the disease is based on the classification criteria, raised by the
      American-European Study Group and which have been built on the European
      preliminary classification criteria, developed in 1992. The association of
      Sjogren's syndrome with lymphoma is well documented as in approximately 5% of
      patients the benign autoimmune process is transformed into a lymphoid malignancy.
      The salivary extranodal marginal zone B-cell lymphomas of the mucosa-associated
      lymphoid tissue type are the most common lymphoma in Sjogren's syndrome. These
      tumors are antigen-stimulated B-cell lymphomas and are characterized by localized
      stage, indolent clinical course, and recurrence in other extranodal sites. Among
      the clinical and serological parameters that have been associated with lymphoma
      development in patients with Sjogren's syndrome, the presence of palpable
      purpura, low C4 and mixed monoclonal cryoglobulinemia constitute the main
      predictive markers; patients displaying these risk factors should be monitored
      closely. The purpose of this review is to discuss the clinical picture, the
      diagnostic procedure, and the malignant lymphoproliferation in the disease.

PMID- 18068859
TI  - Localized scleroderma and systemic sclerosis: is there a connection?
AB  - Excess fibrosis of the skin is a clinical hallmark of both localized scleroderma
      and systemic sclerosis. Localized scleroderma is generally thought to be a skin
      limited disease whereas systemic sclerosis can have a wide range of internal
      organ involvement. Recent data suggest that a subset of patients with juvenile
      localized scleroderma can go on to develop systemic involvement of their disease.
      This raises the question of what the connection is, if any, between localized
      scleroderma and systemic sclerosis.

PMID- 18068860
TI  - Mixed connective tissue disease: what is behind the curtain?
AB  - Although there is still an emotional debate over the existence of mixed
      connective tissue disease, the evidence from animal models suggests that anti
      U1RNP antibodies, similar to other autoantibodies in other connective tissue
      diseases (such as antisynthetase, anticentromere, and antitopoisomerase), play a
      pathophysiological role in this disease. Despite an antiendothelial effect of
      anti-U1RNP antibodies, which is reminiscent of anticentromere antibodies,
      patients with high-titer autoantibodies to U1RNP in the absence of anti-Sm
      antibodies do not usually have or develop typical systemic sclerosis. Instead,
      their severe Raynaud's syndrome is commonly accompanied by arthritis, which can
      be erosive, and by swollen/puffy hands and myositis. Pulmonary arterial
      hypertension is the major life-threatening complication in these patients and
      regular screening for this condition is essential.

PMID- 18068861
TI  - Diagnostic uncertainty in the inflammatory myopathies.
AB  - A group of case histories with appropriate muscle biopsy findings is presented to
      demonstrate some atypical presentations of the inflammatory myopathies.
      Differential diagnostic possibilities are considered in presentations of
      idiopathic polymyositis, statin myotoxicity, the inflammatory component with the
      dysferlinopathies, treated dermatomyositis, a necrotizing myopathy with pipe-stem
      microvascular change, an inflammatory myopathy with abundant macrophages,
      inclusion-body myositis, and the differential diagnosis of problems with
      eosinophilic infiltration in the muscle biopsy. Attention is given to the role of
      membrane attack complex deposition in the microvasculature and the role of major
      histiocompatibility complex-1-expressing muscle fibers indicating activation of
      the endoplasmic reticulum stress response.

PMID- 18068862
TI  - Antiphospholipid syndrome (APS): where does it come from?
AB  - The antiphospholipid syndrome (APS) is the most common acquired thrombophilia. It
      is characterized by venous and arterial thrombosis, recurrent pregnancy loss, and
      various other clinical manifestations in the presence of antiphospholipid
      antibodies (aPL). Like other autoimmune diseases, the etiology of APS derives
      from a combination of genetic and environmental factors. The most significant
      environmental factors in APS are infectious agents, followed by trauma and drugs.
      Infections can induce aPL and, in the catastrophic variant of APS, about one
      third of cases are associated with a clear recent infection. On their formation,
      aPL have been clearly shown to be pathogenic, because they influence all arms of
      the coagulation system and because passive transfer and active immunization
      protocols have demonstrated. Therefore, in a genetically susceptible individual,
      exposure to one or more infectious agent can cause a molecular mimicry and result
      in the production of pathogenic aPL that can induce thrombosis and pregnancy
      loss. Identification of the epitopes within the beta-2-glycoprotein-I molecule
      that serves as the target for autoantibodies makes them the target for
      immunomodulation of the syndrome.

PMID- 18068863
TI  - The treatment of antiphospholipid syndrome: a harmonic contrast.
AB  - The antiphospholipid syndrome (APS) is characterized by a wide variability in
      clinical manifestations. Recommendations for therapy are conditioned by the lack
      of appropriate studies, due either to methodological limitations or excessive
      selection of patients. There is consensus in treating patients with APS and first
      venous thrombosis with warfarin to a target international normalized ratio (INR)
      of 2.3-3.0. However, a recent systematic review including observational studies
      found patients with APS and stroke to be at a high risk of recurrent events. We
      thus recommend a target INR>3.0 in this group. Likewise, the optimal approach for
      women with obstetric manifestations of APS is not completely defined; some
      authors recommend universal aspirin plus heparin whereas others consider aspirin
      in monotherapy useful for women with recurrent early miscarriage only. Correction
      of vascular risk factors and a high-risk management of pregnancy, including
      Doppler studies of the uterine and umbilical vessels, are warranted.
      Hydroxychloroquine and statins are likely to become important in the future.

PMID- 18068864
TI  - The contribution of capillaroscopy to the differential diagnosis of connective
      autoimmune diseases.
AB  - Raynaud's phenomenon (RP) is one of the earliest clinical hallmarks of
      microvascular involvement in several connective autoimmune rheumatic diseases.
      The direct observation of the microvasculature with nailfold videocapillaroscopy
      (NVC) is useful for an early diagnosis of connective autoimmune diseases
      (secondary RP) and differentiation from primary (unsymptomatic) RP. Generally, to
      detect early pathologic capillaroscopic changes, the following parameters are
      considered: presence of enlarged and giant capillaries, haemorrhages,
      disorganization of the vascular array, ramified/bushy capillaries and loss of
      capillaries. Careful capillaroscopic analysis of subjects affected by primary RP
      can detect the earliest signs of the transition to secondary RP and thus
      screening procedures for further differential diagnosis within connective
      autoimmune diseases can be undertaken. In systemic sclerosis, the recognition of
      clear and different NVC morphological patterns ("early", "active", "late") should
      suggest including this analysis in the classification criteria of the disease.

PMID- 18068866
TI  - Hematopoietic cell transplantation for hemoglobinopathies.

PMID- 18068868
TI  - Activities of the frog skin peptide, ascaphin-8 and its lysine-substituted
      analogs against clinical isolates of extended-spectrum beta-lactamase (ESBL)
      producing bacteria.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria are
      becoming increasingly prevalent and their antibiotic resistance necessitates
      novel therapeutic intervention. Ascaphin-8 is a cationic alpha-helical peptide
      that shows broad-spectrum antibacterial activity but is also toxic to human
      erythrocytes (LC(50)= 55 microM). This study assesses the activity of ascaphin-8,
      and a series of l-lysine-substituted analogs, against a range of clinical
      isolates of ESBL-producing bacteria. All ESBL-producing Escherichia coli (MIC=1.5
      6 microM) and Klebsiella pneumoniae (MIC=12.5-25 microM) strains tested were
      susceptible to ascaphin-8, as well as a group of miscellaneous ESBL-producing
      strains (Citrobacter, Salmonella, Serratia, Shigella spp.) (MIC< or = 25 microM).
      The Lys4- and Lys8-substituted analogs were generally the most potent against
      bacteria but showed the highest hemolytic activity. However, the Lys10, Lys14,
      and Lys18 analogs also displayed potent antibacterial activity while showing very
      low hemolytic activity (LC50> 500 microM). An unexpected finding was the
      susceptibility of ESBL-producing Proteus mirabilis strains to ascaphin-8
      (MIC=12.5-25 microM) and its Lys4-substituted analog (MIC= 6 microM), although
      non-ESBL isolates of this organism were resistant to these peptides (MIC> 100
      microM).

PMID- 18068869
TI  - Tachyplesin III and granulocyte-colony stimulating factor enhance the efficacy of
      tazobactam/piperacillin in a neutropenic mouse model of polymicrobial
      peritonitis.
AB  - We investigated the efficacy of tazobactam/piperacillin (TZP), tachyplesin III
      and granulocyte-colony stimulating factor (G-CSF) in an experimental murine
      neutropenic intraabdominal infection. BALB/c male mice were rendered neutropenic
      by intraperitoneal administration of cyclophosphamide on days -4 and -2 pre
      infection. Septic shock was induced by cecal ligation and puncture. Animals
      received intravenously isotonic sodium chloride solution (control group C1),
      1mg/kg of tachyplesin III, 120 mg/kg of TZP, 0.1mg/kg of G-CSF, tachyplesin III
      plus TZP, G-CSF plus TZP and finally tachyplesin III plus G-CSF plus TZP,
      respectively. Lethality, bacterial growth in blood, peritoneum, spleen, liver,
      and mesenteric lymph nodes, endotoxin, IL-6 and TNF-alpha concentrations in
      plasma were evaluated. All compounds reduced the lethality when compared to
      controls. Endotoxin and cytokine plasma levels were significantly higher in TZP
      treated animals compared to tachyplesin III-treated animals. Finally, all drug
      combinations showed to be the most effective treatment in reducing all variables
      measured. Interestingly, the strongest results concerning the bacterial growth
      inhibition, lethality and endotoxemia were obtained when the three compounds were
      contemporaneously administered. The presence of their positive interaction makes
      tachyplesin III and G-CSF potentially valuable as an adjuvant for antimicrobial
      chemotherapy of sepsis.

PMID- 18068870
TI  - Pregnenolone sulfate in the brain: a controversial neurosteroid.
AB  - Pregnenolone sulfate (PREGS) has been shown, either at high nanomolar or at
      micromolar concentrations, to increase neuronal activity by inhibiting GABAergic
      and by stimulating glutamatergic neurotransmission. PREGS is also a potent
      modulator of sigma type 1 (sigma1) receptors. It has been proposed that these
      actions of PREGS underlie its neuropharmacological effects, and in particular its
      influence on memory processes. On the other hand, the PREGS-mediated increase in
      neuronal excitability may become dangerous under particular conditions, for
      example in the case of excitotoxic stress or convulsions. However, the
      physiopathological significance of these observations has recently been put into
      question by the failure to detect significant levels of PREGS within the brain
      and plasma of rats and mice, either by direct analytical methods based on liquid
      chromatography/mass spectrometry (LC/MS) or enzyme linked immunosorbent assay
      (ELISA) with specific antibodies against PREGS, or by indirect gas
      chromatography/mass spectrometry (GC/MS) analysis with improved sample workup.
      These recent results have not come to the attention of a large number of
      neurobiologists interested in steroid sulfates. However, although available
      direct analytical methods have failed to detect levels of PREGS above 0.1-0.3
      ng/g in brain tissue, it may be premature to completely exclude the local
      formation of biologically active PREGS within specific and limited compartments
      of the nervous system. In contrast to the situation in rodents, significant
      levels of sulfated 3beta-hydroxysteroids have been measured in human plasma and
      brain. Previous indirect measures of steroid sulfates by radioimmunoassays (RIA)
      or GC/MS had detected elevated levels of PREGS in rodent brain. The discrepancies
      between the results of different assay procedures have revealed the danger of
      indirect analysis of steroid sulfates. Indeed, PREGS must be
      solvolyzed/hydrolyzed prior to RIA or GC/MS analysis, and it is the released,
      unconjugated PREG which is then quantified. Extreme caution needs to be exercised
      during the preparation of samples for RIA or GC/MS analysis, because the fraction
      presumed to contain only steroid sulfates can be contaminated by nonpolar
      components from which PREG is generated by the
      solvolysis/hydrolysis/derivatization reactions.

PMID- 18068872
TI  - Neuronal inclusion protein TDP-43 has no primary genetic role in FTD and ALS.
AB  - The nuclear TAR DNA binding protein (TDP-43) is deposited in ubiquitin-positive
      inclusions in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis
      (ALS), two clinicopathologically overlapping neurodegenerative diseases. In this
      study we excluded mutations and copy number variations in the gene encoding TDP
      43 (TARDBP) from an extended series of 173 FTD and 237 ALS patients. Further, we
      did not identify association of common genetic variants in these patients. Our
      data implicate that TDP-43 has no primary genetic role in the pathophysiological
      mechanisms underlying central nervous system neurodegeneration in these diseases.

PMID- 18068871
TI  - Presenilin-1 mutation impairs cholinergic modulation of synaptic plasticity and
      suppresses NMDA currents in hippocampus slices.
AB  - Presenilin-1 (PS1) mutations cause many cases of early-onset inherited
      Alzheimer's disease, in part, by increasing the production of neurotoxic forms of
      amyloid beta-peptide (Abeta). However, Abeta-independent effects of mutant PS1 on
      neuronal Ca(2+) homeostasis and sensitivity to excitatory neurotransmitters have
      been reported. Here we show that cholinergic modulation of hippocampal synaptic
      plasticity is impaired in PS1 mutant knockin (PS1KI) mice. Whereas activation of
      muscarinic receptors enhances LTP at CA1 synapses of normal mice, it impairs LTP
      in PS1KI mice. Similarly, mutant PS1 impairs the ability of the cholinesterase
      inhibitor phenserine to enhance LTP. The NMDA current is decreased in CA1 neurons
      of PS1KI mice and is restored by intracellular Ca(2+)chelation. Similar
      alterations in acetylcholine and NMDA receptor-mediated components of synaptic
      plasticity are evident in 3xTgAD mice with PS1, amyloid precursor protein and tau
      mutations, suggesting that the adverse effects of mutant PS1 on synaptic
      plasticity can occur in the absence or presence of amyloid and tau pathologies.

PMID- 18068873
TI  - Synthesis, spectral studies and antiamoebic activity of new 1-N-substituted
      thiocarbamoyl-3-phenyl-2-pyrazolines.
AB  - Thirty new pyrazoline derivatives were synthesized by cyclization of Mannich
      bases with thiosemicarbazides being substituted by different cyclic and aromatic
      amines. The structures of the compounds were elucidated by elemental analyses,
      UV, IR, (1)H and (13)C NMR and ESI-MS spectral data. The in vitro antiamoebic
      activity was evaluated against Entamoeba histolytica in comparison with
      metronidazole used as reference substance. Out of the 30 compounds screened for
      antiamoebic activity, 10 (5, 6, 15, 18, 25-30) were found to be better inhibitors
      of E. histolytica since they showed lesser IC(50) values than metronidazole. The
      preliminary results indicated that the presence of 3-chloro or 3-bromo
      substituent on the phenyl ring at position 3 of the pyrazoline ring enhanced the
      antiamoebic activity as compared to unsubstituted phenyl ring. The study suggests
      that the preliminary activity of these compounds may further be explored for the
      development of new targets for amoebiasis.

PMID- 18068874
TI  - [Management of cytomegalovirus infections in patients treated with
      immunosuppressive drugs for chronic inflammatory diseases].
AB  - INTRODUCTION: For patients with chronic inflammatory disease treated by
      immunosuppressive agents (for example: rheumatoid arthritis or systemic lupus
      erythematosus), there are no available guidelines in medical literature on the
      use of antiviral agents for the management of symptomatic cytomegalovirus (CMV)
      infection. EXEGESIS: A patient treated by methotrexate for a spondylarthritis
      presented a CMV infection manifested with persistent fever and pneumonia. CMV
      pp65 antigenemia was of 120 positive nuclei for 100,000 cells. Treatment with
      valganciclovir allowed a prompt recovery, while treatment by methotrexate was
      maintained. CONCLUSION: Symptomatic CMV infection evolution is unpredictable and
      potentially severe in patients with chronic inflammatory diseases receiving
      immunosuppressive agents. Although there is no data issued from clinical trials,
      the observation reported in this article and the publications of similar cases in
      the medical literature indicate that treatment with valganciclovir seems worth to
      be used in this context. Stopping immunosuppressive therapy does not seem
      mandatory.

PMID- 18068875
TI  - Nutritional goals, prescription and delivery in a pediatric intensive care unit.
AB  - BACKGROUND & AIMS: The aim of this study was to compare prescription and delivery
      of nutrition to predefined nutritional targets, and identify risk factors
      associated with inadequate nutritional intake. METHODS: In 84 mechanically
      ventilated critically ill children with length of stay on the PICU of at least 3
      days, we observed prescribed and delivered percentages of predefined targets for
      intake of calories and macronutrients during a 10-months study period. Factors
      associated with inadequate intake were identified. RESULTS: On the third day of
      admission 92.9% of the patients received nutritional therapy. The caloric goal
      was reached on day 5, mainly supplied by fat and carbohydrates. Mean actual daily
      protein delivery was about 75% of the target during the entire study period. Use
      of catecholamines or neuromuscular blocking agents was a risk factor for caloric
      undernutrition, whereas there were no specific risk factors for overnutrition.
      CONCLUSIONS: Nutritional therapy should be started in the early phase of critical
      illness, including adequate supply of protein. In order to prevent deficits to
      accumulate, parenteral nutrition should be added in an early phase, if
      nutritional needs cannot be met by enteral nutrition.

PMID- 18068877
TI  - Revaccination does not improve an observed deficit in antibody responses in
      Pakistani adults born of a lower birth weight.
AB  - We have previously shown that the generation of antibodies to a polysaccharide
      vaccine (Typhim Vi) is compromised in Pakistani adults born of a lower birth
      weight. To assess whether this represents a true B-cell-dependent deficit, we
      revaccinated subjects with a second dose of the same vaccine and with a
      polysaccharide-protein conjugate vaccine to a different polysaccharide antigen
      (conjugated Haemophilus influenzae type b (Hib) vaccine). Anti-Vi IgG levels
      remained positively correlated with birth weight (p=0.0284) but no associations
      were observed between anti-Hib IgG levels and size at birth. These findings
      indicate that small size at birth results in a poor antibody response to
      vaccination with a polysaccharide antigen vaccine in adulthood, even following a
      second dose of the vaccine. No such association was observed in response to a
      polysaccharide-protein conjugate vaccine indicating an early-life programming
      effect on the generation of antibodies during a B-cell-dependent immune response.

PMID- 18068876
TI  - Phase I study of a candidate vaccine based on recombinant HIV-1 gp160 (MN/LAI)
      administered by the mucosal route to HIV-seronegative volunteers: the ANRS VAC14
      study.
AB  - One goal of HIV vaccination is to achieve high mucosal levels of specific
      secretory IgA (SIgA). In order to elicit specific SIgA antibodies against human
      immunodeficiency virus type-1 (HIV-1), a vaccine must be administered by the
      mucosal route, to the nasal or vaginal mucosa for example. We report here the
      results of the first phase I, randomized, open-label trial designed to assess the
      mucosal tolerability and immunogenicity of a candidate vaccine (recombinant
      protein HIV-1 gp160MN/LAI with or without DC-Chol adjuvant) administered by the
      nasal or vaginal route. Thirty-four female volunteers with a mean age of 46 years
      were vaccinated. There were 465 adverse events, of which 65 were considered
      related to the vaccine. No severe adverse events were related to the vaccine, and
      no difference in terms of tolerability was observed between the sites of
      vaccination or between the vaccine formulations. None of the volunteers reported
      that study participation affected their intimate or broader social relationships.
      No anti-gp160 activity was found between week 4 and week 48 in serum, saliva, or
      cervicovaginal and nasal secretions. These results show that a mucosal HIV
      vaccine can be well tolerated when administered by the nasal or vaginal route.

PMID- 18068879
TI  - Arsenic contamination of soils and agricultural plants through irrigation water
      in Nepal.
AB  - This study monitored the influence of arsenic-contaminated irrigation water on
      alkaline soils and arsenic uptake in agricultural plants at field level. The
      arsenic concentrations in irrigation water ranges from <0.005 to 1.014 mg L(-1)
      where the arsenic concentrations in the soils were measured from 6.1 to 16.7 mg
      As kg(-1). The arsenic content in different parts of plants are found in the
      order of roots>shoots>leaves>edible parts. The mean arsenic content of edible
      plant material (dry weight) were found in the order of onion leaves (0.55 mg As
      kg(-1))>onion bulb (0.45 mg As kg(-1))>cauliflower (0.33 mg As kg(-1))>rice (0.18
      mg As kg(-1))>brinjal (0.09 mg As kg(-1))>potato (<0.01 mg As kg(-1)).

PMID- 18068878
TI  - Can the rasp be used to predict intra-operatively the primary stability that can
      be achieved by press-fitting the stem in cementless hip arthroplasty?
AB  - BACKGROUND: Success of cementless hip stems implantation depends mainly on
      primary stability which, in turn, depends on the degree of press-fitting
      achieved, and optimal medullary canal filling by the selected stem size. Stem
      size, based on templating and pre-operative planning software, only partially
      avoids stem mis-sizing. Mis-sizing can produce implant instability and/or wasting
      the wrong-sized stem. METHODS: An intra-operative device was designed that
      enabled real-time measurement of rasp-bone micromotions by applying torque
      manually. Rasp stability was assessed in vitro in seven femurs after femoral
      canal preparation when the rasp was fully seated. Then, primary implant stability
      was assessed with the stem press-fitted in the position indicated as optimal by
      the surgeon. Torque-micromotion curves were compared for the rasp and the stem.
      Finally, the protocol was applied to two hip patients. FINDINGS: Rasp stability
      micromotions were successfully measured in all in vitro specimens and all
      patients. The slope of the initial part of the rasp torque-micromotion curve was
      correlated with the slope of the stem curve (correlation coefficient=0.798, P
      value=0.001). The entire procedure for measuring rasp stability added less than
      two minutes to the 75-80-min operating time. INTERPRETATION: This study indicates
      that the rasp stability can be used to predict the maximal primary stability that
      can eventually be achieved by the selected stem size. Early prediction of stem
      stability enables correcting the stem size, if necessary, before the press
      fitting procedure is initiated, thus saving operating time and the cost of a new
      stem.

PMID- 18068880
TI  - A multi-stage sampling strategy for the delineation of soil pollution in a
      contaminated brownfield.
AB  - A multi-stage sampling strategy, based on sequential Gaussian simulation, was
      presented to optimize the step-wise selection of a small numbers of additional
      samples to delineate soil pollution. This strategy was applied to a Belgian
      brownfield of 5.2 ha polluted with lead (Pb). Starting from an initial number of
      240 samples in stage 1, additional samples were added, 25 per stage, and the
      reduction of the uncertainty in the Pb delineation was monitored. Twenty stages
      were used. Already in stage 6 a local optimum was found based on the median
      conditional coefficient of variation. An independent validation confirmed that
      this index was to be preferred over the median conditional variance. So for the
      brownfield considered our procedure indicated that 365 selected samples would
      have been sufficient, representing a gain of 70.7% in sampling effort compared to
      current practice which resulted in a sampling effort of 1245 samples.

PMID- 18068881
TI  - Calibration of the Chemcatcher passive sampler for monitoring selected polar and
      semi-polar pesticides in surface water.
AB  - Passive sampling is a powerful method for continuous pollution monitoring, but
      calibration experiments are still needed to generate sampling rates in order to
      estimate water concentrations for polar compounds. We calibrated the Chemcatcher
      device with an uncovered SDB-XC Empore disk as receiving phase for 12 polar and
      semi-polar pesticides in aquatic environments in flow-through tank experiments at
      two water flow velocities (0.135 m/s and 0.4 m/s). In the 14-day period of
      exposure the uptake of test substances in the sampler remained linear, and all
      derived sampling rates R(s) were in the range of 0.1 to 0.5 L/day. By
      additionally monitoring the release of two preloaded polar pesticides from the
      SDB-XC disks over time, very high variation in release kinetics was found, which
      calls into question the applicability of performance reference compounds. Our
      study expands the applicability of the Chemcatcher for monitoring trace
      concentrations of pesticides with frequent occurrence in water.

PMID- 18068883
TI  - Safety evaluation of Elsholtzia splendens extracts: assessment of acute toxicity
      and mutagenicity.
AB  - Much attention is recently gained for Elsholtzia splendens extracts and issue on
      their usage is raised due to their biological properties. However, there is no
      sufficient background information on toxicological evaluation of E. splendens
      extracts to give an assurance of safety for developing dietary supplements and
      functional foods. The objective of this study was to evaluate safety on E.
      splendens extracts using acute oral toxicity, bacterial reverse mutation, and
      chromosome aberration test. Total flavonoids within E. splendens were extracted
      with 80% of methanol by a reflux condenser. Both female and male mice were orally
      administrated E. splendens extracts at the dose of 0, 500, 1000, and 2000 mg/kg
      body weight/day. Mutagenicity of the extracts was evaluated in a bacterial
      reverse mutation assay using histidine requiring Salmonella typhimurium (TA 98,
      TA 100, TA 1535, and TA 1537) and tryptophan-requiring Escherichia coli
      (WP2uvrA). In vitro chromosome aberration assay in Chinese Hamster Lung (CHL) was
      conducted to evaluate genotoxicity. Single administration of dose levels of 500,
      1000, and 2000 mg/kg body weight/day to mice for 15 days did not produce any
      significant mortality, clinical signs, body weight loss, and gross findings. E.
      splendens extracts in the range of 156.3-5000 microg/plate did not induce
      mutagenicity in S. typhimurium and E. coli with and without metabolic activation
      system. Any significant chromosomal aberration was not observed in CHL cells 6h
      after treating with the extract at the concentrations of 1250, 2500, and 5000
      microg/mL in absence and presence of metabolic activation system. However,
      frequency of chromosomal aberration in 22 h after treatment without metabolic
      activation system was increased with showing a pattern of dose-response
      relationship. The highest concentration of 5000 microg/mL significantly induced
      chromosomal aberration. E. splendens extracts may induce chromosomal structure
      abnormality in CHL cells. This study suggests that further study is needed to
      assess the potential genotoxic effects of E. splendens extracts.

PMID- 18068884
TI  - Genotoxicity testing of four benzyl derivatives in the Drosophila wing spot test.
AB  - Food flavourings are an essential element in foods. Benzyl derivatives are the
      food additives which are used for increasing the taste of foods and beverages. In
      this study, different concentrations of four benzyl derivatives (benzaldehyde,
      benzyl acetate, benzyl alcohol and benzoic acid) used as flavour ingredients have
      been evaluated for genotoxicity in the wing somatic mutation and recombination
      test (SMART) of Drosophila melanogaster. Third-instar larvae trans-heterozygous
      for two genetic markers mwh and flr, were treated at different concentrations
      (0.1, 0.5, 1, 10, 25 and 50mM) of the test compounds. Wings of the emerging adult
      flies were scored for the presence of spots of mutant cells, which can result
      from either somatic mutation or mitotic recombination. Also lethal doses of
      benzyl derivatives used as flavour ingredients were determined in the
      experiments. For the evaluation of genotoxic effects, the frequencies of spots
      per wing in the treated series were compared to the control group, which is
      distilled water. Chemicals used were ranked as benzaldehyde, benzyl acetate,
      benzyl alcohol and benzoic acid according to their genotoxic effects. The present
      study shows that intensive administration of benzyl derivatives used as
      flavouring agents may have a significant genotoxic effects.

PMID- 18068882
TI  - Empirical evidence of cognitive vulnerability for depression among children and
      adolescents: a cognitive science and developmental perspective.
AB  - We summarize and integrate research on cognitive vulnerability to depression
      among children and adolescents. We first review prospective longitudinal studies
      of the most researched cognitive vulnerability factors (attributional style,
      dysfunctional attitudes, and self-perception) and depression among youth. We next
      review research on information processing biases in youth. We propose that the
      integration of these two literatures will result in a more adequate test of
      cognitive vulnerability models. Last, we outline a program of research addressing
      methodological, statistical, and scientific limitations in the cognitive
      vulnerability literature.

PMID- 18068885
TI  - Over-expression and siRNA of a novel environmental lipopolysaccharide-responding
      gene on the cell cycle of the human hepatoma-derived cell line HepG2.
AB  - Lipopolysaccharide (LPS) is the toxic determinant for Gram-negative bacterium
      infection. The individual response to LPS was related to its gene background. It
      is necessary to identify new molecules and signaling transduction pathways about
      LPS. The present study was undertaken to evaluate the effects of a novel
      environmental lipopolysaccharide-responding (Elrg) gene on the regulation of
      proliferation and cell cycle of the hepatoma-derived cell line, HepG2. By means
      of RT-PCR, the new molecule of Elrg was generated from a human dental pulp cell
      cDNA library. Expression level of Elrg in HepG2 cells was remarkably upgraded by
      the irritation of LPS. Localization of Elrg in HepG2 cells was positioned mainly
      in cytoplasm. HepG2 cells were markedly arrested in the G1 phase by over
      expressing Elrg. The percentage of HepG2 cells in G1 phase partly decreased after
      Elrg-siRNA. In conclusion, Elrg is probably correlative with LPS responding. Elrg
      is probably a new protein in cytoplasm which plays an important role in
      regulating cell cycle. The results will deepen our understanding about the
      potential effects of Elrg on the human hepatoma-derived cell line HepG2.

PMID- 18068886
TI  - The potential protective role of alpha-lipoic acid against acetaminophen-induced
      hepatic and renal damage.
AB  - The potential protective role of alpha-lipoic acid (alpha-LA) in acetaminophen
      (APAP)-induced hepatotoxicity and nephrotoxicity was investigated in rats.
      Pretreatment of rats with alpha-LA (100mg/kg) orally protected markedly against
      hepatotoxicity and nephrotoxicity induced by an acute oral toxic dose of APAP
      (2.5 g/kg) as assessed by biochemical measurements and by histopathological
      examination. None of alpha-LA pretreated animals died by the acute toxic dose of
      APAP. Concomitantly, APAP-induced profound elevation of nitric oxide (NO)
      production and oxidative stress, as evidenced by increasing of lipid peroxidation
      level, reducing of glutathione peroxidase (GSH-Px) activity and depleting of
      intracellular reduced glutathione (GSH) level in liver and kidney, were
      suppressed by pretreatment with alpha-LA. Similarly, daily treatment of rats with
      a smaller dose of alpha-LA (25mg/kg) concurrently with a smaller toxic dose of
      APAP (750 mg/kg) for 1 week protected against APAP-induced hepatotoxicity and
      nephrotoxicity. This treatment also completely prevented APAP-induced mortality
      and markedly inhibited APAP-induced NO overproduction and oxidative stress in
      hepatic and renal tissues. These results provide evidence that inhibition of NO
      overproduction and maintenance of intracellular antioxidant status may play a
      pivotal role in the protective effects of alpha-LA against APAP-induced hepatic
      and renal damage.

PMID- 18068887
TI  - Influence of operator skill on microleakege of total-etch and self-etch bonding
      systems.
AB  - OBJECTIVES: To evaluate the influence of operator skill on microleakage in class
      V restorations using simplified bonding systems. METHODS: Two cavities were
      carried out on the buccal and lingual surfaces of 50 human bicuspid teeth. The
      teeth were randomly assigned to two groups according to the operator's skill:
      student group and expert group. The two cavities of each tooth were randomly
      treated with Adper Scotchbond 1 XT (total-etch adhesive) and Adper Prompt L-Pop
      (self-etch adhesive). All cavities were restored with a 0.2mm thick layer of
      flowable composite (Filtek flow) followed by one bulk increment of resin
      composite (Filtek Supreme XT). Specimens were thermocycled, immersed in 2%
      methylene blue and sectioned in a bucco-lingual plane. They were then examined
      under a stereomicroscope and scored according to microleakage. The data was
      subjected to a multilevel statistical model. RESULTS: At the dentine margin the
      microleakage resulting from both the self-etch adhesive and the total-etch one
      was similar in the student and in the expert groups. The interaction term skill x
      adhesive was not statistically significant (p=0.4156). At the enamel margin the
      self-etch adhesive microleakage within the student group resulted lower than that
      within the expert group. On the other hand, the total-etch adhesive microleakage
      within the expert group resulted lower than that within the student group. The
      interaction term skill x adhesive was statistically significant (p=0.0037).
      CONCLUSIONS: Both the adhesives used were sensitive to operator skill in
      obtaining a reliable seal with the enamel. On the dentine, both adhesives
      demonstrated little sensitivity to operator skill.

PMID- 18068888
TI  - Physical strain on advanced life support providers in different out of hospital
      environments.
AB  - OBJECTIVES: To examine to what extent the type of emergency medical
      transportation influences the physical response of advanced life support
      providers. BACKGROUND: Providing external chest compression during resuscitation
      is physically exhausting. If the decision is made to bring the patient to a
      hospital undergoing resuscitation procedures, there are usually two options for
      transportation: ambulance vehicles or helicopters. There should be discussion on
      deciding which means of transportation should be preferred, because there is
      evidence that the quality of rescuers performance influences patient's outcome.
      METHODS: The study was a randomised crossover trial comparing physical strain on
      11 European Resuscitation Council (ERC) approved healthcare professionals during
      external chest compression in different environments: (a) moving ambulance
      vehicle vs. (b) flying helicopter, and both compared to (c) staying at the scene
      (control). MAIN OUTCOME MEASURES: Difference in heart rate to systolic blood
      pressure ratio after 8 min of external chest compression. Secondary outcomes were
      BORG-rate of perceived exertion scale, blood pressure, serum lactate, and a Nine
      Hole Peg Test. RESULTS: Mean heart rate to systolic blood pressure ratio was
      0.89+/-0.21 in the ambulance vehicle compared to 1.01+/-0.21 in the flying
      helicopter (p=0.04) There were no significant differences in the secondary
      outcome parameters. Perceived exertion increased by resuscitation time in all
      groups. CONCLUSION: External chest compression CPR is possible in a flying
      helicopter as it is in a moving ambulance vehicle. There is no clinical relevant
      difference in physical strain during ALS between a flying helicopter and a moving
      ambulance car. As would be expected, the exertion increases with duration of CPR.

PMID- 18068889
TI  - The outcome of gastroschisis after a prenatal diagnosis or a diagnosis only at
      birth. Recommendations for prenatal surveillance.
AB  - OBJECTIVES: To establish in infants with gastroschisis whether outcome is
      different when comparing a prenatal diagnosis with a diagnosis only at birth with
      the intention to develop a prenatal surveillance protocol. Intestinal atresia
      established after birth and preterm versus term delivery were studied as risk
      factors. STUDY DESIGN: All 24 fetuses and 9 infants diagnosed with gastroschisis
      and referred to our tertiary center between January 1991 and June 2003 were
      studied retrospectively. RESULTS: The infants of the prenatal subset delivered at
      our tertiary center and 18 survived. There were two pregnancy terminations, three
      intrauterine deaths at 19, 33 and 36 weeks respectively and one neonatal death.
      All nine infants in the postnatal subset survived. Eight were out born and one
      was delivered at our tertiary center. Prenatal bowel dilatation did not correlate
      with outcome. Between the prenatal and postnatal subset no significant difference
      in outcome of live-born infants was established. For four infants with intestinal
      atresia a significant difference was demonstrated for induction of preterm labour
      (P<0.05), duration of parenteral nutrition (P<0.01), number of additional
      surgical procedures (P<0.001) and length of hospital stay (P<0.01). The fifteen
      infants born prior to 37 weeks of gestation spent a significantly longer period
      in hospital compared to those delivered at term. When the cases with bowel
      atresia were excluded this difference was no longer present. Five of the 33 cases
      were diagnosed with associated anomalies which mainly involved the urinary tract.
      CONCLUSION: Neonatal outcome of live born infants following a prenatal diagnosis
      of gastroschisis is not different from a diagnosis at birth. The presence of
      intestinal atresia is the most important prognostic factor for morbidity. The
      supplemental value of prenatal diagnosis to the outcome of infants with
      gastroschisis may be in the prevention of unnecessary intrauterine death and
      detection of intestinal complications. A proposed surveillance protocol for
      fetuses with gastroschisis focused on intrauterine signs of pending distress such
      as a dilated stomach, intra abdominal bowel dilatation with peristalsis, notches
      in the umbilical artery Doppler signal, development of polyhydramnios and an
      abnormal CTG registration may improve outcome.

PMID- 18068890
TI  - Self-aggregation of free base porphyrins in aqueous solution and in DMPC
      vesicles.
AB  - Free base porphyrin (PPhe), derivatized with aminosulfonyl groups linked to the
      aromatic amino acid phenylalanine at the meso-positions, was mixed with DMPC
      vesicles. The resulting interaction was studied by absorption, steady-state and
      transient state fluorescence, at different pHs. At pH=2 to pH=9, the
      aforementioned porphyrin predominates as an aggregated species, with a co-facial
      arrangement of the molecules taking into account the blue shift of the Soret band
      (414 nm for the monomer and 401 nm for the aggregate). Upon interaction with DMPC
      vesicles, the competing hydrophobic interactions with the bilayer destabilize the
      aggregated species in favor of monomer incorporation. Fluorescence lifetimes also
      show that the long component assigned to the monomer contributes only 30% to the
      overall decay in solution (e.g. pH=7.0) whereas in DMPC vesicles this
      contribution increases up to 85% independent of the solution pH, which confirms a
      location of the probe in an environment "protected" from free water. The picture
      changes completely in the case of TSPP, an anionic porphyrin which does not
      incorporate in DMPC vesicles. Remarkably, at pH=2.5 all the experimental findings
      point to the self-assembling of the porphyrin units in J-aggregates induced at
      the surface of the DMPC vesicle. In fact, upon removal of the aqueous solvent, we
      could define by fluorescence lifetime imaging microscopy (FLIM) regions where the
      fluorescence lifetime is that characteristic of the J-aggregate (<tau(F)> 0.11
      ns).

PMID- 18068891
TI  - Thyroid hormone receptor expression during metamorphosis of Atlantic halibut
      (Hippoglossus hippoglossus).
AB  - Flatfish such as the Atlantic halibut (Hippoglossus hippoglossus) undergo a
      dramatic metamorphosis that transforms the pelagic, symmetric larva into a
      benthic, cranially asymmetric juvenile. In common with amphibian metamorphosis,
      flatfish metamorphosis is under endocrine control with thyroid hormones being
      particularly important. In this report we confirm that tri-iodothyronine (T(3))
      levels peak at metamorphic climax during halibut metamorphosis. Moreover, we have
      isolated cDNA clones of TRalpha and TRbeta genes and confirmed the presence in
      halibut of two TRalpha isoforms (representing the products of distinct genes) and
      two TRbeta isoforms (generated from a single gene by alternative splicing). Real
      time PCR was used to assess expression of these genes during metamorphosis.
      TRbeta shows the most dramatic expression profile, with a peak occurring during
      metamorphic climax.

PMID- 18068892
TI  - Extracorporeal membrane oxygenation resuscitation for traumatic brain injury
      after decompressive craniotomy.
AB  - Acute cardiopulmonary failure in patients with increased intracranial pressure is
      a significant management challenge to physicians. We report on a 21-year-old
      patient with traumatic brain injury who developed intractable hypoxemia and
      hypotension after undergoing a decompressive craniotomy. Venoarterial
      extracorporeal membrane oxygenation was initiated to resuscitate the patient.
      Extracorporeal membrane oxygenation is considered contraindicated in patients
      with intracranial bleeding because systemic heparin is needed during the support
      of extracorporeal membrane oxygenation. We describe our successful experience in
      tackling this dilemma.

PMID- 18068893
TI  - Green tea catechin as a chemical chaperone in cancer prevention.
AB  - Green tea catechins have recently gained significant acceptance as a cancer
      preventive, and one of the important features of catechins is their interactions
      with various target molecules. We recently found a functional and structural
      similarity between catechins and chaperones: Stochastic conformational analysis
      in silico revealed numerous conformations of (-)-epigallocatechin gallate, (-)
      epicatechin gallate and (-)-epigallocatechin, showing a unique flexibility and
      mobility of the catechin molecules and suggesting the significance of a galloyl
      group in conformational variation. Since these conformations result in
      interaction with various types of molecules, we think that green tea catechin
      induces cancer preventive activity mediated through a chaperone-like property.

PMID- 18068894
TI  - NS5ATP9, a gene up-regulated by HCV NS5A protein.
AB  - Non-structural protein 5A (NS5A) appears to interact with a variety of cellular
      proteins and play an important role in mediating cell growth, cellular signaling
      pathways and pathogenesis of hepatitis C virus (HCV). NS5ATP9 was identified as a
      NS5A trans-activated protein in suppression subtractive hybridization (SSH), and
      the regulation was confirmed by luciferase reporter assay and quantitative real
      time PCR (qRT-PCR). A minimal promoter region contained within the 211bp
      (nucleotides -161 to +50bp) immediately upstream of the transcription initiation
      site. NS5ATP9 is a NS5A up-regulation gene which may play a role in the
      pathogenesis of HCV-associated hepatocellular carcinoma.

PMID- 18068895
TI  - Exploring effects of chemical structure on azo dye decolorization characteristics
      by Pseudomonas luteola.
AB  - This follow-up study tended to provide a systematic comparison for how the
      variation of functional groups and molecular structures present in model azo dyes
      affects color removal capability of Pseudomonas luteola. As sulfo group at methyl
      orange (p-MO) or carboxyl group at 4-(4'-dimethylaminophenylazobenzoic acid)
      sodium salt (denoted p-MR) were both para to azo bond, the ranking of
      decolorization rate was p-MO>p-MR due to the stronger electron-withdrawing effect
      of the sulfo group. For isomers, when the functional groups (sulfo group at 2-(4'
      dimethylamino-phenylazo) benzenesulfonic acid sodium salt (o-MO) or carboxyl
      group at methyl red (o-MR)) were ortho to azo bond, the decolorization rate
      significantly decreased (e.g., p-MO>o-MO or p-MR>>o-MR) likely due to steric
      hindrance near azo linkage(s). Similarly, for phenolic azo dyes the series of
      decolorization rate was 3-(4'-dimethylaminophenylazo) phenol (m-OH)>2-(4'
      dimethylaminophenylazo) phenol (o-OH). Apparently, azo dyes with different
      properties of substituent on aromatic ring could affect the efficiency of
      biodecolorization of P. luteola. Moreover, the relative position (e.g., ortho,
      meta, para) of the substituent to azo bond could also influence the capability of
      biodecolorization of P. luteola. Regarding the electronic effect, azo dyes with
      stronger electron-withdrawing group (e.g., sulfo group) at specific positions
      (e.g., at para) could be more easily biodecolored than those with a carboxyl
      group.

PMID- 18068896
TI  - Homogeneous catalytic ozonation of C.I. Reactive Red 2 by metallic ions in a
      bubble column reactor.
AB  - This study elucidates the decolorization of C.I. Reactive Red 2 (RR2) by
      homogeneous catalytic ozonation. The effects of pH and catalyst dosage were
      evaluated in O3/Mn(II), O3/Fe(II), O3/Fe(III), O3/Zn(II), O3/Co(II) and O3/Ni(II)
      systems. In O3/Mn(II), O3/Fe(II) and O3/Fe(III) systems, increasing the catalyst
      concentration increased the rate of RR2 decolorization; however, further
      increasing the catalyst concentration caused no further significant increase.
      When 0.6 mM catalyst was added, the decolorization rates of O3/Mn(II), O3/Fe(II),
      O3/Fe(III), O3/Zn(II), O3/Co(II) and O3/Ni(II) systems at pH 2 were 3.295, 1.299,
      1.278, 1.015, 0.843 and 0.822 min(-1), respectively. Under all of the
      experimental conditions, the decolorization efficiency of catalytic ozonation
      exceeded that of ozonation alone. The decolorization rate markedly exceeds the
      TOC removal rate in all tested systems. The effect of the radical scavenger on
      the catalytic ozonation processes suggests that the decolorization reaction in
      catalytic ozonation systems proceeds by mainly radical-type mechanisms, except in
      the O3/Mn(II) system.

PMID- 18068897
TI  - Effect of landfill leachate on cell cycle, micronucleus, and sister chromatid
      exchange in Triticum aestivum.
AB  - With increasing use of municipal solid waste landfills for waste disposal, the
      leachate generated has become a serious environmental concern. Therefore, it is
      important to set up simple and accurate methods for monitoring leachate toxicity.
      In the present study, the physiological and genetic toxicity of the leachate,
      generated from Xingou Municipal Landfill in China, were investigated with
      Triticum aestivum (wheat) bioassay. The results indicate that the lower leachate
      concentrations stimulated the germination, growth and cell division, and did not
      induce obvious increase in micronucleus (MN) frequency in root tips; while the
      higher concentrations inhibited the processes, and significantly augmented the MN
      frequency in a concentration- and time-dependent manner. In addition, pycnotic
      cells (PNC) and sister chromatid exchange (SCE) occurred in root tips at all
      leachate concentrations tested, and the frequencies had positive relation with
      the treatment concentration and time. The results imply that components of
      leachate from the landfill may be genotoxic in plant cells, and exposure to
      leachate in the aquatic environment may pose a potential genotoxic risk to
      organisms. The results also suggest that the wheat bioassay is efficient, simple
      and reproducible in monitoring genotoxicity of the leachate.

PMID- 18068898
TI  - Application of response surface methodology for optimization of lead biosorption
      in an aqueous solution by Aspergillus niger.
AB  - Response surface methodology was applied to optimize the removal of lead ion by
      Aspergillus niger in an aqueous solution. Experiments were conducted based on a
      rotatable central composite design (CCD) and analyzed using response surface
      methodology (RSM). The biosorption process was investigated as a function of
      three independent factors viz. initial solution pH (2.8-7.2), initial lead
      concentration (8-30 mg/l) and biomass dosage (1.6-6 g/l). The optimum conditions
      for the lead biosorption were found to be 3.44, 19.28 mg/l and 3.74 g/l,
      respectively, for initial solution pH, initial lead ion concentration and biomass
      dosage. Lead biosorption capacity on dead A. niger fungal biomass was enhanced by
      pretreatment using NaOH. Under these conditions, maximum biosorption capacity of
      the biomass for removal of lead ions was obtained to 96.21%. The desirability
      function was used to evaluate all the factors and response in the biosorption
      experiments in order to find an optimum point where the desired conditions could
      be obtained. The A. niger particles with clean surface and high porosity may have
      application as biosorbent for heavy metal removal from wastewater effluents.

PMID- 18068899
TI  - 13C NMR study of the effect of aerobic treatment of olive mill wastewater (OMW)
      on its lipid-free content.
AB  - Olive mill wastewater was treated by an aerobic bio-process at different values
      of pH (with or without addition of lime), for 45 days on a laboratory scale, to
      evaluate the reduction of the organic load. The lipid content showed an
      appreciable change in relation to the applied treatment both for total lipids and
      for the different fractions (neutral lipids, monoglycerides and phospholipids).
      13C NMR spectroscopy was performed on initial and final samples both raw and
      after lipid extraction. The main spectral differences were observed in the C
      alkyl region (0-50 ppm), in the C O-alkyl/N-alkyl region (50-110 ppm), and in the
      C-carboxylic (160-200 ppm) region, providing information on the alterations
      occurring in the different biochemical entities composing this complex biomatrix
      (e.g. lipids and carbohydrates) according to the treatment.

PMID- 18068900
TI  - Influence of exercise on serum brain-derived neurotrophic factor concentrations
      in healthy human subjects.
AB  - The effect of short-term exercise (15 min step-exercise) on serum brain-derived
      neurotrophic factor (BDNF) levels was evaluated in healthy human subjects.
      Results showed a short-term, significant increase in serum BDNF levels after
      exercise. Intra-individual differences in serum BDNF levels were remarkably small
      on the rest day and also when compared to rest values on the day of the exercise
      test. Inter-individual differences, on the other hand, were larger by comparison.
      The result of this study supports the need for larger sample size in studies on
      BDNF changes in psychiatric disorders or psychiatric drug effects.

PMID- 18068902
TI  - Shape dependence of the capacitance of scanning capacitance microscope probes.
AB  - The capacitance of approximately conical scanning capacitance microscope probes
      placed perpendicularly over a conducting plane has been modelled using the finite
      element method. The dependence on tip/surface distance, radius of curvature of
      the tip apex, cone angle and height has been analysed. Both shielded and
      unshielded probes have been considered. The fits of obtained dependences have
      been combined into an analytic approximation of the capacitance as a function of
      tip/surface distance, radius of curvature, cone angle and height. The results can
      be used to estimation of stray capacitance, achievable lateral resolution and
      contrast.

PMID- 18068903
TI  - Near-field scanning optical microscope probe analysis.
AB  - In this article results of a comparison of two NSOM probe characterization
      methods are presented. Scanning electron microscopy analysis combined with
      electromagnetic field modeling using the finite difference in time domain method
      are compared with measured far-field radiation diagrams of NSOM probes. It is
      shown that measurement of far-field radiation diagrams can be an efficient tool
      for daily checking of the NSOM probes quality. Moreover, it is shown that the
      inner probe geometry has large influence on the directional radiation of an NSOM
      probe and the far-field radiation diagram can be used as a simple method to
      distinguish between different probe geometries.

PMID- 18068901
TI  - Estrogen alters spinal NMDA receptor activity via a PKA signaling pathway in a
      visceral pain model in the rat.
AB  - Pain symptoms in several chronic pain disorders in women, including irritable
      bowel syndrome, fluctuate with the menstrual cycle suggesting a gonadal hormone
      component. In female rats, estrogens modulate visceral sensitivity although the
      underlying mechanism(s) are unknown. In the present study the effects of 17-beta
      estradiol on N-methyl-D-aspartate (NMDA) receptor signaling of colorectal
      nociceptive processing in the spinal cord were examined. Estrogen receptor alpha
      and the NR1 subunit of the NMDA receptor are co-expressed in dorsal horn neurons,
      supporting a direct action of estradiol on NMDA receptors. Intrathecal
      administration of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic
      acid (APV) dose-dependently attenuated the visceromotor response with greater
      potency in ovariectomized (OVx) rats compared to OVx with estradiol replacement
      (E2) rats. Estradiol significantly increased protein expression of NR1 in the
      lumbosacral spinal cord compared to OVx rats. Colorectal distention significantly
      increased phosphorylation of NR1ser-897, a PKA phosphorylation site on the NR1
      subunit in E2, but not OVx rats. Intrathecal administration of a PKA inhibitor
      significantly attenuated the visceromotor response, decreased NR1 phosphorylation
      and increased the potency of APV to attenuate the visceromotor response compared
      to vehicle-treated E2 rats. These data suggest that estradiol increases spinal
      processing of visceral nociception by increasing NMDA receptor NR1 subunit
      expression and increasing site-specific receptor phosphorylation on the NR1
      subunit contributing to an increase in NMDA receptor activity.

PMID- 18068904
TI  - Planar diffracted-beam interferometry/holography.
AB  - A method to interfere planar electron diffracted beams that have been created by
      a primary electron beam passing through a crystal specimen has been invented and
      referred to as planar diffracted-beam interferometry/holography (planar DBI/H).
      Planar DBI/H is able to measure the intensity and coherence properties of the
      diffracted electron beams. When the diffracted electron beams are energy
      filtered, planar DBI/H is also able to measure the intensity and coherence
      properties of the zero-loss electrons, phonon-loss electrons and plasmon-loss
      electrons. These coherence properties are useful to help our understanding of the
      Stobbs factor and the properties of advanced materials, necessary for our
      understanding of nanoscience and the development of nanotechnology.

PMID- 18068906
TI  - Is TGF-beta important for the evolution of subcutaneuos chronic mycoses?
AB  - Jorge Lobo's and chromoblastomycosis are chronic deep mycosis that clinically
      manifests as keloid and verrucous polymorphic lesions of solid consistency and
      variable size that contain small scales and crusts. Few studies are available in
      the literature characterizing the in situ cellular and humoral immune response,
      especially the involvement of cytokines which immunosuppressive and fibrogenic
      effects as the TGF-beta. The hypothesis of the present paper is explaining the
      possible mechanism of this cytokine in cutaneous lesions pathology in
      chromoblastomycosis and lacaziosis (Jorge Lobo's disease). The results of this
      investigation are a new hypothesis for ethiopatogenesis of these diseases: TGF
      beta is a double effect that follows fibrosis and immunosuppression in local
      skin.

PMID- 18068905
TI  - Contingency management reduces injection-related HIV risk behaviors in heroin and
      cocaine using outpatients.
AB  - Intravenous drug use is a major vector of HIV transmission. We assessed whether
      contingency management (CM), in which participants earn reinforcers for drug
      abstinence, reduces HIV risk behaviors in methadone-maintained opiate- and
      cocaine-using outpatients. Participants (n=116) were randomly assigned to prize
      based CM or to receipt of prize draws noncontingently on a schedule yoked to the
      CM group. Both groups received methadone and individual counseling throughout
      treatment. The HIV-Risk Taking Behaviour Scale was administered in written
      questionnaire form at 2-week intervals (HRBS; [Darke, S., Hall, W., Heather, N.,
      Ward, J., & Wodak, A. (1991). The reliability and validity of a scale to measure
      HIV risk-taking behaviour among intravenous drug users. AIDS, 5, 181-185]). A
      mediation analysis was conducted to determine whether abstinence from opiates and
      cocaine mediated the effect of CM on HRBS scores. Changes in HRBS scores over
      time differed significantly by treatment (F(9,334)=2.4, p<0.05), with HRBS scores
      decreasing over time in the CM group to a greater extent than in the
      noncontingent control group. Participants in the CM group had significantly lower
      rates of simultaneous cocaine/opiate-positive urine specimens than those in the
      noncontingent control group during CM treatment (F(1,111)=6.8, p=0.01). The
      relationship between treatment condition and HRBS scores was mediated by
      abstinence. CM targeted toward cocaine and heroin use produces significant
      reductions in injection-related drug-taking behaviors associated with heightened
      risk for getting or transmitting HIV.

PMID- 18068907
TI  - [Vaginal hysterectomy using electrofusion: a study of 96 cases].
AB  - OBJECTIVE: To compare ligature by electrofusion versus sutures in the practice of
      vaginal hysterectomy. STUDY DESIGN: This is a retrospective study on 96 patients
      completed over a period of 47 months. Patients were allocated into two groups:
      the electrofusion "suture-free" group (n=54) and the "suture" control group
      (n=42). Designed-end points were operating time, postoperative pain, duration of
      postoperative hospitalization and perioperative complications. RESULTS: In the
      electrofusion group, the operating time was significantly reduced (51.3+/-22.6
      min versus 67.6+/-20.1 min) as well as the reported postoperative pain (based on
      the visual analog scale - VAS) (1.9+/-2.0 versus 3.5+/-2.3). The average morphine
      consumption rate and the timing of postoperative morphine administration were
      lower in the electrofusion group (22.4+/-31.0mg versus 45.4+/-51.3 mg and 22.4+/
      13.4 h versus 29.4+/-18.8 h, respectively). Moreover, in the electrofusion group
      there was less need for additional analgesics (1.9+/-2.0 versus 3.5+/-2.3) and
      the hospital-stay was shorter (4.2+/-1.3 days versus 5.0+/-1.0 days). There was
      no significant difference between the two groups in regard to perioperative
      complications. CONCLUSION: The use of electrofusion in vaginal hysterectomy
      appears to be a reliable ligation technique which reduces significantly the
      operating time, the postoperative pain and the length of postoperative
      hospitalization.

PMID- 18068908
TI  - [To screen or to prevent cervical carcinoma?].

PMID- 18068909
TI  - [Teaching physician-patient relationship using role-play in obstetrics and
      gynecology].
AB  - AIM: The aim of this study was to report our experience concerning a role-playing
      approach for the teaching of physician-patient relationship. METHODS: The role
      playing two-day course was designed to be highly interactive for a small group
      (ten participants). Opinions were gathered by an anonymous structured
      questionnaire (ten questions) completed by the participants and focused on their
      view of the play role and the physician-patient relationship. RESULTS: The
      opinions of the participants were highly positive; all appreciated the courses.
      The strong emotional involvement was considered beneficial for all of them,
      sharing emotional aspects of the profession, and usefulness in clarifying
      opinions on the physician-patient relationship. CONCLUSION: The positive opinions
      recorded during this experience suggest the benefit of implementing non
      conventional educational approaches, such as role-play, to highlight the relative
      importance of physician-patient relationship in obstetrics and gynecology.

PMID- 18068910
TI  - Understanding auditory distance estimation by humpback whales: a computational
      approach.
AB  - Ranging, the ability to judge the distance to a sound source, depends on the
      presence of predictable patterns of attenuation. We measured long-range sound
      propagation in coastal waters to assess whether humpback whales might use
      frequency degradation cues to range singing whales. Two types of neural networks,
      a multi-layer and a single-layer perceptron, were trained to classify recorded
      sounds by distance traveled based on their frequency content. The multi-layer
      network successfully classified received sounds, demonstrating that the
      distorting effects of underwater propagation on frequency content provide
      sufficient cues to estimate source distance. Normalizing received sounds with
      respect to ambient noise levels increased the accuracy of distance estimates by
      single-layer perceptrons, indicating that familiarity with background noise can
      potentially improve a listening whale's ability to range. To assess whether
      frequency patterns predictive of source distance were likely to be perceived by
      whales, recordings were pre-processed using a computational model of the humpback
      whale's peripheral auditory system. Although signals processed with this model
      contained less information than the original recordings, neural networks trained
      with these physiologically based representations estimated source distance more
      accurately, suggesting that listening whales should be able to range singers
      using distance-dependent changes in frequency content.

PMID- 18068911
TI  - Differential regulation of HOXA9 expression by nuclear factor kappa B (NF-kappaB)
      and HOXA9.
AB  - HOXA9 is a homeobox transcription factor expressed in endothelial cells (EC) and
      its expression is rapidly downregulated during EC activation by inflammatory
      signals like tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide
      (LPS). Recently, we have shown that HOXA9 overexpression prevents EC activation
      by inhibiting NF-kappaB activity, which suggests that HOXA9 downregulation is an
      essential event for EC activation. The present study is directed towards
      understanding the mechanism of HOXA9 regulation during EC activation. Here we
      show that nuclear factor-kappaB (NF-kappaB) activation is an essential step for
      HOXA9 downregulation. Deletion analyses of HOXA9 promoter in EC and NF-kappaB
      knockout cells have shown that NF-kappaB is a major transcription factor that is
      absolutely required for HOXA9 downregulation. Our 5' deletion analysis of HOXA9
      promoter shows that NF-kappaB response element is localized within first 400
      nucleotides, while minimal basal promoter is within 100 nucleotides upstream of
      its transcriptional start site. We demonstrate that HOXA9 regulates its own
      expression by positive feedback mechanism. To define mechanism by which HOXA9
      autoregulates its expression, we show that HOXA9 DNA binding and transactivation
      domains are essential.

PMID- 18068912
TI  - An evaluation of the immunogenicity and protective responses to Brachyspira
      hyodysenteriae recombinant SmpB vaccination.
AB  - SmpB is an outer membrane protein of Brachyspira hyodysentariae that is present
      in some strains of the bacterium. It shares the same locus as SmpA, but all
      strains tested to date contain either one protein or the other, never both. In
      this study we have evaluated the efficacy of vaccination with SmpB to elicit
      immune responses in mice and to protect against a subsequent challenge. Immunised
      mice develop humoral and cellular responses to SmpB delivered as either a DNA
      vaccine or a recombinant protein, although the magnitude of the responses is
      greater after protein vaccination. The responses induced after protein
      vaccination offer moderate protection against disease and indicate that SmpB has
      potential as a component of a vaccine against B. hyodysentariae.

PMID- 18068913
TI  - A limited role for SsrA/B in persistent Salmonella Typhimurium infections in
      pigs.
AB  - Virulence genes regulated by the SsrA/B system are indispensable for systemic
      disease in BALB/c mice. The role of this regulating system in the pathogenesis of
      Salmonella Typhimurium infections in pigs is not documented. In the present
      study, the interactions of Salmonella Typhimurium and an ssrA/B mutant were
      compared in vitro and in vivo. The ssrA/B mutant strain displayed decreased
      Salmonella Pathogenicity Island 2 (SPI-2) expression levels, showed a replication
      defect in mouse macrophages and was attenuated in a mouse model after oral
      inoculation. Using real time qRT-PCR and a porcine ileal loop model, it was shown
      that the ssrA/B mutant strain was not significantly attenuated in overall
      virulence and SPI-1 expression in specific. Flowcytometric analysis demonstrated
      that the ssrA/B mutant strain was defective in intracellular replication in
      porcine macrophages. After oral inoculation of piglets with the wild type strain
      or the ssrA/B mutant strain, the animals of both groups excreted Salmonella and
      were colonized by Salmonella to the same extent. In an intravenous mixed
      infection model, the ssrA/B mutant strain was defective in the colonization of
      several internal organs. These results suggest that the ssrA/B gene of Salmonella
      Typhimurium plays a limited role in the persistent intestinal colonization of
      pigs.

PMID- 18068914
TI  - Detection of hepatitis E virus in archived German wild boar serum samples.
AB  - Hepatitis E is a rare human disease in Central Europe commonly imported from
      endemic regions. For autochthonous infections a zoonotic transmission from pigs,
      deer and wild boar is assumed. Using three different RT-PCR protocols, hepatitis
      E virus (HEV) RNA was detected in 10 out of 189 (5.3%) serum samples collected in
      1995/1996 from wild boars in Germany. Sequence analysis indicates a close
      relationship with genotype 3 isolates of pigs and humans from the Netherlands and
      Japan. The results indicate that HEV is present in Germany since more than 10
      years and that wild boar may function as a reservoir for HEV.

PMID- 18068916
TI  - Gateways and tools for drug delivery: endocytic pathways and the cellular
      dynamics of cell penetrating peptides.
AB  - A major goal in drug delivery is to be able to design a macromolecular entity
      that utilises an endocytic pathway to deliver a bioactive payload into a
      malfunctioning cell. However, the effectiveness of this approach may be
      constrained by insufficient information regarding the fate of the delivery vector
      within the confines of the endo-lysosomal network. Successful drug delivery
      through this mechanism is therefore dependent on an equal high level of
      understanding of the specific endocytic pathways that are inherent in the target
      cell and the traffic and fate of the macromolecule within endocytic organelles.
      Cell penetrating peptides (CPPs) are promising candidate vectors for delivering
      macromolecules, however, there is little consensus regarding their exact
      mechanism of uptake. This review highlights the numerous endocytic pathways and
      sorting mechanisms that may deliver CPPs to a number of cellular destinations.
      Our use of non-adherent leukaemia cell lines to study the cellular dynamics of
      CPPs HIV-TAT and octaarginine is also discussed.

PMID- 18068915
TI  - Hormone therapy is associated with preserved smooth muscle structure and dilation
      in the arterial vasculature of the leg in older women.
AB  - Long-term hormone therapy (HT) is associated with reduced intima-medial thickness
      (IMT), an established risk factor for atherosclerotic disease, in the femoral
      artery of healthy older women relative to age-matched non-hormone users. However,
      the influence of continuous, long-term HT on the relation between age, IMT, and
      smooth muscle dilation has not been investigated in the popliteal artery, an
      artery prone to stiffening and calcification. In the present study, popliteal
      artery IMT and smooth muscle dilation (the increase in diameter to sublingual
      nitroglycerin, NTG) were assessed with Doppler ultrasound in young (Y: n=16; age
      23+/-1 [mean+/-S.E.M.]), older non-HT (O non-HT: n=14; age 69+/-1), and older HT
      (O HT: n=8; age 67+/-1) healthy women. The approximately 0.5 mm increase in
      resting diameter observed in older non-HT women relative to young women was
      absent in older HT women, as was the age-related increase in IMT (Y: 0.52+/-0.02
      mm; O non-HT: 0.63+/-0.02 mm; O HT: 0.56+/-0.02 mm; p<0.05 for age and hormone
      comparisons). NTG dilation (percent change above rest) was similarly attenuated
      in older non-HT women (Y: 8.6+/-1%; O non-HT: 3.0+/-0.7%; O HT: 7.4+/-1.7%;
      p<0.05 for age and hormone comparisons), and NTG dilation was inversely related
      to IMT (p<0.01). Collectively, these results suggest that long-term, continuous
      HT may alleviate the detrimental effects of aging on both structural changes and
      smooth muscle dilation of the popliteal artery in healthy women.

PMID- 18068918
TI  - Preparation of bilayer-core osmotic pump tablet by coating the indented core
      tablet.
AB  - In this paper, a bilayer-core osmotic pump tablet (OPT) which does not require
      laser drilling to form the drug delivery orifice is described. The bilayer-core
      consisted of two layers: (a) push layer and (b) drug layer, and was made with a
      modified upper tablet punch, which produced an indentation at the center of the
      drug layer surface. The indented tablets were coated by using a conventional pan
      coating process. Although the bottom of the indentation could be coated, the side
      face of the indentation was scarcely sprayed by the coating solution and this
      part of the tablet remained at least partly uncoated leaving an aperture from
      which drug release could occur. Nifedipine was selected as the model drug. Sodium
      chloride was used as osmotic agent, polyvinylpyrrolidone as suspending agent and
      croscarmellose sodium as expanding agent. The indented core tablet was coated by
      ethyl cellulose as semipermeable membrane containing polyethylene glycol 400 for
      controlling the membrane permeability. The formulation of core tablet was
      optimized by orthogonal design and the release profiles of various formulations
      were evaluated by similarity factor (f(2)). It was found that the optimal OPT was
      able to deliver nifedipine at an approximate zero-order up to 24 h, independent
      on both release media and agitation rates. The preparation of bilayer-core OPT
      was simplified by coating the indented core tablet, by which sophisticated
      technology of the drug layer identification and laser drilling could be
      eliminated. It might be promising in the field of preparation of bilayer-core
      OPT.

PMID- 18068919
TI  - The influence of cosurfactants and oils on the formation of pharmaceutical
      microemulsions based on PEG-8 caprylic/capric glycerides.
AB  - In the present study the effect of type and concentration of a cosurfactant and
      oil on the ability of nonionic surfactant PEG-8 caprylic/capric glycerides
      (Labrasol) to solubilize both oil and water phases was evaluated. Seven different
      cosurfactants (polyglyceryl-6 dioleate (Plurol Oleique) (PO), polyglyceryl-6
      isostearate (Plurol Isostearique (PI), polyglyceryl-4 isostearate (Isolan GI 34)
      (IGI34), octoxynol-12 (and) polysorbate 20 (Solubilisant gamma) 2421) (SG2421),
      octoxynol-12 (and) polysorbate 20 (and) PEG-40 hydrogenated castor oil
      (Solubilisant gamma 2429) (SG2429), PEG-40 hydrogenated castor oil (Cremophor) RH
      40) (CRH40) and diethyleneglycol monoethyl ether (Transcutol) and six oils
      (isopropyl myristate, ethyl oleate, decyl oleate, medium chain triglycerides,
      mineral oil and olive oil) were used in phase behaviour studies of a quaternary
      system Labrasol/cosurfactant/oil/water. The amount of surfactant required to
      completely homogenize equal masses of oil and water to form a single phase
      microemulsion (termed as balanced microemulsion) (S min, %w/w), the minimal
      concentration of the surfactant/cosurfactant blend required to produce a balanced
      microemulsion (SCoS min, %w/w) as well as the maximum concentration of water
      solubilized in investigated surfactant/oil and surfactant/cosurfactant/oil
      mixtures (W(max), %w/w) were determined. The obtained results indicated that
      Labrasol showed a good efficiency in the presence of lower molecular volume fatty
      acid esters with a preferred chemical structure such as isopropyl myristate (S
      min 56.14% (w/w); W(max) 12.28% (w/w)). Oils with high molecular volume (olive
      oil and mineral oil) do not result in microemulsion formation. Transcutol
      decreased the capacity of Labrasol for solubilization of oil and water phases.
      The tendency of Labrasol to solubilize both, water and oil phases, was favoured
      by polyglycerol-6 ester type of cosurfactants (PO and PI) while the influence of
      the polyglycerol-4 ester (IGI34) as well as of polyoxyethylene type of
      cosurfactants (CRH40, SG2421 and SG2429) on the surfactant efficiency, was not
      significant. Furthermore, the results revealed the significant influence of the
      surfactant/cosurfactant mass ratio (K(m)) on synergistic effect between
      polyglyceryl-6 esters and Labrasol in the formation of microemulsions using
      isopropyl myristate as oil phase. Optimized microemulsion systems were stabilized
      with Labrasol/polyglyceryl-6 esters blend at K(m) 5:5 (SCoS min, 27.5% (w/w) and
      W(max), 71.43% (w/w) for PI; SCoS min, 29.18% (w/w) and W(max), 65.00% (w/w) for
      PO) and the electrical conductivity measurement results for optimized balanced
      microemulsions showed that their structures were highly conductive indicating a
      bicontinuous microstructure.

PMID- 18068920
TI  - Dangnyohwan improves glucose utilization and reduces insulin resistance by
      increasing the adipocyte-specific GLUT4 expression in Otsuka Long-Evans Tokushima
      Fatty rats.
AB  - AIM OF THE STUDY: Dangnyohwan (DNH) has been used for treatment of diabetes
      mellitus. However, the exact cellular and molecular mechanisms underlying the
      beneficial effects of DNH are not well understood. Therefore, we investigated how
      DNH improves hyperglycemia and insulin resistance in obese-type diabetes model.
      METHODS AND MATERIALS: We examined the effect of DNH on the expression of glucose
      transporter 4 (GLUT4), GLUT4 translocation, and glucose transport activity in
      muscle and adipose tissues from Otsuka Long-Evans Tokushima Fatty (OLETF) and
      Long-Evans Tokushima Otsuka (LETO) rats. RESULTS: DNH ameliorated hyperglycemia
      and impaired glucose tolerance (IGT) observed in 26- and 42-week-old male OLETF
      rats. The basal and insulin-stimulated [14C]2-Deoxyglucose (2DG) uptake was
      significantly increased in adipocytes from DNH-treated OLETF rats, as compared
      with untreated OLETF rats. The expression level of GLUT4 was markedly decreased
      (by 90-95%) in the adipose tissue of OLETF rats, whereas DNH treatment
      drastically increased the expression of GLUT4 within 8 weeks. DNH improved GLUT4
      recruitment stimulated by insulin in both the 26- and 42-week-old OLETF rat
      adipocytes. CONCLUSION: These results suggest that DNH could exert the beneficial
      effects on hyperglycemia and insulin resistance by increasing the expression and
      insulin-stimulated translocation of GLUT4 in OLETF rat adipocytes.

PMID- 18068921
TI  - Animal models to test drugs with potential antidiabetic activity.
AB  - Although medicinal plants have been historically used for diabetes treatment
      throughout the world, few of them have been validated by scientific criteria.
      Recently, a large diversity of animal models has been developed to better
      understand the pathogenesis of diabetes mellitus and new drugs have been
      introduced in the market to treat this disease. The aim of this work was to
      review the available animal models of diabetes and some in vitro models which
      have been used as tools to investigate the mechanism of action of drugs with
      potential antidiabetic properties. In addition, a MEDLINE/PUBMED search for
      articles on natural products, pancreatectomy and diabetes mellitus treatment
      published between 1996 and 2006 was done. In the majority of the studies, natural
      products mainly derived from plants have been tested in diabetes models induced
      by chemical agents. This review contributes to the researcher in the
      ethnopharmacology field to designs new strategies for the development of novel
      drugs to treat this serious condition that constitutes a global public health.

PMID- 18068922
TI  - Spectral characteristics of EEG gamma rhythms associated with epileptic spasms.
AB  - To elucidate the pathophysiology of epileptic spasms, unaveraged time-frequency
      spectra of spasm-associated EEG gamma rhythms were investigated in 15 patients
      with West syndrome or related disorders. Using these unaveraged spectra, we were
      able to investigate in detail various aspects of the structure of ictal gamma
      rhythms that could not be examined using averaged spectra. The characteristics of
      the ictal gamma peaks (peak frequency, power, duration, and the number of peaks
      in each brain-region for each spasm) were statistically evaluated with respect to
      their differences among the brain regions and over the time-course of the
      clusters. Our findings were as follows: (1) Gamma peaks were clearly detected in
      most spectra and generally had a similar pattern in each spasm, which repeated in
      clusters. (2) The mean frequency of gamma peaks was 69.2+/-16.8Hz, and the number
      of peaks in each brain region of each spasm was 1.83+/-1.16. (3) The
      occipitoparietal gamma peaks had significantly greater power and longer duration
      than the frontocentral peaks. (4) The frequency of the gamma peaks was higher in
      the mid phase of clusters than in the ending, and it tended to have a positive
      correlation with its latency from the preceding beta peak. An analysis of the
      ictal gamma rhythms might give some insight into the generative mechanism of
      spasms.

PMID- 18068923
TI  - Altered oxidant-mediated intraneuronal zinc mobilization in a triple transgenic
      mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is responsible for the most common form of dementia
      among elderly people. Signature features of the AD brain are intra/extracellular
      deposits of beta-amyloid (Abeta) and neurofibrillary tangles composed of
      hyperphosphorylated tau. Recent evidence indicates that in AD altered Zn(2+)
      homeostasis can play an important role in the development of the disease as the
      cation promotes Abeta oligomerization and plaque formation. In this study, we
      investigated whether intraneuronal Zn(2+) homeostasis is affected by known "pro
      AD factors" such as mutant forms of the amyloid precursor (APP), presenilin-1
      (PS1), and tau proteins. Oxidative stress is a potent trigger for mobilization of
      intracellular free Zn(2+) ([Zn(2+)](i)) and we therefore evaluated ROS-driven
      [Zn(2+)](i) rises in neurons obtained from triple transgenic AD mice (3xTg-AD)
      that express mutant APP, PS1 and tau. In this study, [Zn(2+)](i) rises triggered
      by prolonged exposure to the membrane-permeant oxidizing agent 2,2'
      dithiodipyridine were found to be significantly higher in 3xTg-AD neurons when
      compared to control cultures, suggesting that neuronal expression of pro-AD
      factors can facilitate altered Zn(2+) homeostasis.

PMID- 18068924
TI  - Thin-section CT of lung without ECG gating: 64-detector row CT can markedly
      reduce cardiac motion artifact which can simulate lung lesions.
AB  - PURPOSE: Motion artifacts, which can mimic thickened bronchial wall and the
      cystic appearance of bronchiectasis, constitute a potential pitfall in the
      diagnosis of interstitial or bronchial disease. Therefore, purpose of our study
      was to evaluate whether 64-detector row CT (64-MDCT) enables a reduction in
      respiratory or cardiac motion artifacts in the lung area on thin-section CT
      without ECG gating, and to examine the correlation between cardiac motion
      artifact and heart rate. MATERIALS AND METHODS: Thirty-two patients with
      suspected diffuse lung disease, who underwent both 8- and 64-MDCT (gantry
      rotation time, 0.5 and 0.4s, respectively), were included. The heart rates of an
      additional 155 patients were measured (range, 48-126 beats per minute; mean, 76
      beats per minute) immediately prior to 64-MDCT, and compared to the degree of
      cardiac motion artifact. Two independent observers evaluated the following
      artifacts on a monitor without the knowledge of relevant clinical information:
      (1) artifacts on 8- and 64-MDCT images with 1.25-mm thickness and those on 64
      MDCT images with 0.625-mm thickness in 32 patients; and (2) artifacts on 64-MDCT
      images with 0.625-mm thickness in 155 patients. RESULTS: Interobserver agreement
      was good in evaluating artifacts on 8-MDCT images with 1.25-mm thickness
      (weighted Kappa test, kappa=0.61-0.71), and fair or poor in the other evaluations
      (kappa<0.31). Two observers stated that cardiac motion artifacts were more
      significant on 8-MDCT than on 64-MDCT in all 32 patients. Statistically
      significant differences were found at various checkpoints only in comparing
      artifacts between 8- and 64-MDCT for 1.25-mm thickness (Wilcoxon's signed-rank
      test, p<0.0017). Cardiac motion artifacts on 64-MDCT had no significant
      correlation with heart rate (Spearman's correlation coefficient by rank test).
      CONCLUSION: The high temporal resolution of 64-MDCT appears to reduce cardiac
      motion artifact that can affect thin-section scans of the lung parenchyma.

PMID- 18068925
TI  - Can contrast-enhanced ultrasonography replace multidetector-computed tomography
      in the detection of liver metastases from colorectal cancer?
AB  - PURPOSE: To compare the sensitivity and specificity of contrast-enhanced
      ultrasonography (CEUS) and 4-slice multidetector-computed tomography (MDCT) in
      the detection of liver metastases in patients with colorectal cancer (CRC).
      MATERIALS AND METHODS: Candidates for this prospective study were 461 consecutive
      patients referred to the Department of Colorectal Surgery, Aarhus University
      Hospital with primary or local recurrence of CRC. The patients underwent liver
      ultrasonography (US), CEUS, MDCT and intraoperative ultrasonography (IOUS). Fine
      needle biopsy was performed on all suspicious lesions. The examinations were
      interpreted blindly and the combination of US, CEUS, biphasic MDCT, IOUS, follow
      up and biopsy was the gold standard. RESULTS: Three hundred and sixty-five
      patients were included. All patients had undergone preoperative US, CEUS and MDCT
      and 65.5% had received IOUS. The gold standard found liver metastases in 54
      patients (14.8%). Multidetector CT found significantly more metastases than CEUS
      in 15 (28%) of the patients (p=0.02). In a patient-by-patient analysis MDCT had a
      non-significantly higher sensitivity in the detection of liver metastases
      compared to CEUS (0.89 versus 0.80, p=0.06). The specificity of CEUS (0.98) was
      slightly better than that of MDCT (0.94) (p=0.02). CONCLUSION: Multidetector CT
      found significant more metastases than CEUS, and MDCT had in patient-by-patient
      analysis a non-significant better sensitivity (p=0.06) in detecting liver
      metastases in patients with CRC.

PMID- 18068926
TI  - Evaluating glycogen signal contamination in muscle by (13)C MRS of the liver.
AB  - To evaluate the contamination of glycogen signal synthesized in skeletal muscle
      by that in the liver, long-term monitoring of over 7 h of in vivo [1-(13)C]
      glycogen synthesis/degradation at the right abdomen and left shoulder was
      achieved using a 3.0-T clinical MR system. (13)C MR spectra without localization
      were obtained from five healthy volunteers before and after oral administration
      of 85 g of d-glucose, including 10 g of 99% [1-(13)C] glucose. In all volunteers,
      the relative signal intensities at the abdomen to those at shoulder were about
      two- to fivefold, and those of time-course changes at the abdomen and shoulder
      were dissimilar. It is considered that the quantity of muscle-synthesized
      glycogen signal at the abdomen is less than that at the shoulder because of the
      lesser muscle volume at the abdomen, and it may be less affected for evaluating
      glycogen synthesis/degradation in the liver even without localization pulses.

PMID- 18068927
TI  - Automatic correction of in-plane bulk motion artifacts in self-navigated radial
      MRI.
AB  - Radial MRI is typically used for scans that are sensitive to unavoidable motion.
      While the translational motion artifact can be easily removed from the radial
      trajectory data by phase correction, correction of rotational motion still
      remains a challenge in radial MRI. We present a novel method to refocus the image
      corrupted by view-to-view motion in the view-interleaved radial MRI data. In this
      method, the error in rotational view angles was modeled as a polynomial function
      of the view order and the model parameters were estimated by minimizing the self
      navigator image metrics such as image entropy, gradient entropy, normalized
      gradient squared and mean square difference. Translational motion correction was
      conducted by aligning the projection profiles. Simulation studies were conducted
      to demonstrate the robustness of both translational and rotational motion
      correction methods in different noise levels. The proposed method was
      successfully applied to correct for motion of healthy subjects. Substantial
      motion correction with relative error of less than 5% was achieved by using
      either first- or second-order model with the image metrics. This study
      demonstrates the potential of the method for motion-sensitive applications.

PMID- 18068928
TI  - Rapid passive MR catheter visualization for endovascular therapy using
      nonsymmetric truncated k-space sampling strategies.
AB  - Passive catheter tracking guidance by MRI is a promising approach for
      endovascular therapy that may have several clinical advantages over the more
      frequently employed active MR approaches. However, real-time MR passive tracking
      is problematic because it is difficult to have an image update rate >1 Hz and
      preserve adequate spatial and image contrast resolution. One solution for
      improving real-time temporal performance is the use of nonsymmetric truncated k
      space sampling strategies, which acquire only a fraction of the data in both the
      readout and phase-encoding directions. This article investigated these
      acquisition strategies in combination with using (a) multicycle projection
      dephaser (mcPD) gradients for background suppression and (b) the projection-onto
      convex sets (POCS) algorithm to reconstruct the images. The use of mcPD gradients
      allowed the data sampling strategies to exploit the k-space energy structure of
      the catheter, and POCS allowed reconstruction of high-quality MR images that were
      suitable for real-time passive catheter tracking and demonstrated improved
      geometric representations of catheter width and tip position compared to zero
      filling. The use of nonsymmetric truncated k-space reduced the total acquisition
      time.

PMID- 18068929
TI  - Volumetric q-space imaging by 3D diffusion-weighted MRI.
AB  - High b-value diffusion magnetic resonance imaging (MRI) enables us to detect far
      smaller architectures, by using q-space analysis, than the resolution in
      conventional MRI. Average displacement, one of the q-space parameters,
      quantitatively reflects architecture size and is very useful in observing small
      changes in microstructures in vivo (e.g., neurodegeneration, tumor heterogeneity,
      and others). Diffusion-weighted imaging (DWI) is performed by a two-dimensional
      (2D) multislice method; however, due to finite slice thickness and slice gap,
      there is a partial-volume effect that makes it difficult to detect the net q
      space signal. On the other hand, three-dimensional (3D) MRI, having the
      advantages of very thin slice thickness and no slice gap (contiguous slices),
      allows volumetric evaluation acquired in a small isotropic voxel, as compared to
      2D multislice imaging. Little is known about the isotropic high-resolution 3D DWI
      application to q-space analysis. In this study, we have developed and implemented
      a high b-value 3D DWI sequence, applied q-space analysis to study the reliability
      of high b-value 3D DWI and obtained a microscopic analytical map with isotropic
      high resolution and less contamination.

PMID- 18068930
TI  - Optimized 3D bright blood MRI of aortic plaque at 3 T.
AB  - PURPOSE: To evaluate the feasibility of an optimized bright blood MRI protocol at
      3 T in combination with contrast agent administration for the detection and
      characterization of aortic high-risk plaques for the improved workup of acute
      stroke patients. MATERIALS AND METHODS: ECG synchronized T1-weighted 3D gradient
      echo MRI was performed in 45 acute stroke patients. Data were acquired with high
      near isotropic spatial resolution (approximately 1 mm(3)) covering the entire
      thoracic aorta. To compensate for breathing and vessel motion artifacts, images
      were collected using respiratory navigator gating in combination with short
      diastolic data acquisition windows adjusted on a patient-by-patient basis. In
      patients with aortic plaques > or =3 mm in thickness, gadolinium contrast agent
      was administered and both pre- and post-contrast T1-weighted 3D measurements with
      identical vessel coverage were performed. RESULTS: Bright blood 3D MRI detected
      33 high-risk plaques with an average maximum plaque thickness of 4.2+/-1.0 mm in
      23 of 45 acute stroke patients. The availability of pre- and post-contrast images
      acquired within the same session enhanced the identification of calcified plaque
      components in 77% of all analyzed plaques: post-contrast MRI clearly improved the
      delineation of hypointense plaque cores in 23 of 30 cases and assisted in the
      classification of core shape and of core fraction. CONCLUSION: 3D bright blood
      MRI at 3 T was feasible for the detection of aortic high-risk sources and may
      help to improve the detection of causes of cerebral embolism in acute stroke
      patients.

PMID- 18068932
TI  - MRI with TRELLIS: a novel approach to motion correction.
AB  - A motion-correcting pulse sequence and reconstruction algorithm, termed TRELLIS,
      is presented. k-Space is filled using orthogonal overlapping strips and the
      directions for phase- and frequency-encoding are alternated such that the
      frequency-encode direction always runs lengthwise along each strip. The overlap
      between strips is used both for signal averaging and to produce a system of
      equations that, when solved, quantifies the rotational and translational motion
      of the object. Results obtained from simulations with computer-generated
      phantoms, a purpose-built moving phantom, and in human subjects show the method
      is effective. TRELLIS offers some advantages over existing techniques in that k
      space is sampled uniformly and all acquired data are used for both motion
      detection and image reconstruction.

PMID- 18068931
TI  - Quantitative myocardial distribution volume from dynamic contrast-enhanced MRI.
AB  - The objective of this study was to investigate if dynamic contrast-enhanced
      magnetic resonance imaging (MRI) can be used to quantitate the distribution
      volume (v(e)) in regions of normal and infarcted myocardium. v(e) reflects the
      volume of the extracellular, extravascular space within the myocardial tissue. In
      regions of the heart where an infarct has occurred, the loss of viable cardiac
      cells results in an elevated v(e) compared to normal regions. A quantitative
      estimate of the magnitude and spatial distribution of v(e) is significant because
      it may provide information complementary to delayed enhancement MRI alone. Using
      a hybrid gradient echo-echoplanar imaging pulse sequence on a 1.5T MRI scanner,
      12 normal subjects and four infarct patients were imaged dynamically, during the
      injection of a contrast agent, to measure the regional blood and tissue
      enhancement in the left ventricular (LV) myocardium. Seven of the normal subjects
      and all of the infarct patients were also imaged at steady-state contrast
      enhancement to estimate the steady-state ratio of contrast agent in the tissue
      and blood (Ct/Cb) - a validated measure of v(e). Normal and infarct regions of
      the LV were manually selected, and the blood and tissue enhancement curves were
      fit to a compartment model to estimate v(e). Also, the effect of the vascular
      blood signal on estimates of v(e) was evaluated using simulations and in the
      dynamic and steady-state studies. Aggregate estimates of v(e) were 23.6+/-6.3% in
      normal myocardium and 45.7+/-3.4% in regions of infarct. These results were not
      significantly different from the reference standards of Ct/Cb (22.9+/-6.8% and
      42.6+/-6.3%, P=.073). From the dynamic contrast-enhanced studies, approximately 1
      min of scan time was necessary to estimate v(e) in the normal myocardium to
      within 10% of the steady-state estimate. In regions of infarct, up to 3 min of
      dynamic data were required to estimate v(e) to within 10% of the steady-state
      v(e) value. By measuring the kinetics of blood and tissue enhancement in the
      myocardium during an extended dynamic contrast enhanced MRI study, v(e) may be
      estimated using compartment modeling.

PMID- 18068933
TI  - Neural correlates of a clinical continuous performance test.
AB  - Functional magnetic resonance imaging (fMRI) was performed in 30 healthy adults
      to identify the location, magnitude, and extent of activation in brain regions
      that are engaged during the performance of Conners' Continuous Performance Test
      (CPT). Performance on the task during fMRI was highly correlated with performance
      on the standard Conners' CPT in the behavioral testing laboratory. An extensive
      neural network was activated during the task that included the frontal,
      cingulate, parietal, temporal, and occipital cortices; the cerebellum and the
      basal ganglia. There was also a network of brain regions which were more active
      during fixation than task. The magnitude of activation in several regions was
      correlated with reaction time. Among regions that were more active during task,
      the overall volume of supratentorial activation and cerebellar activation was
      greater in the left hemisphere. Frontal activation was greater in dorsal than in
      ventral regions, and dorsal frontal activation was bilateral. Ventral frontal
      region and parietal lobe activation were greater in the right hemisphere. The
      volume of clusters of activation in the extrastriate ventral visual pathway was
      greater in the left hemisphere. This network is consistent with existing models
      of motor control, visual object processing and attentional control and may serve
      as a basis for hypothesis-driven fMRI studies in clinical populations with
      deficits in Conners' CPT performance.

PMID- 18068934
TI  - Tigecycline activity tested against 11808 bacterial pathogens recently collected
      from US medical centers.
AB  - Tigecycline activity was evaluated against 11808 pathogens isolated from 30 US
      medical centers. Susceptibility testing was performed by reference broth
      microdilution methods. Tigecycline (MIC(50/90), 0.12/0.25 microg/mL) was highly
      active against Staphylococcus aureus and coagulase-negative staphylococci,
      regardless of oxacillin resistance. This glycylcycline (MIC(50), 0.12 microg/mL)
      was 8- and 16-fold more potent than penicillin and linezolid against enterococci
      and was the most potent agent tested versus Streptococcus pneumoniae. Against
      Enterobacteriaceae, tigecycline (MIC(90), 1 microg/mL; 98.9% susceptible) was as
      active as imipenem. This study demonstrated the sustained potency of tigecycline
      against contemporary clinically relevant Gram-positive and Gram-negative
      pathogens; tigecycline resistance was rare (0.3%).

PMID- 18068935
TI  - Real-time polymerase chain reaction detection of Neisseria meningitidis in
      formalin-fixed tissues from sudden deaths.
AB  - Accurate identification of meningococcal sudden deaths is needed to avoid
      underestimation of the true incidence of the disease. This study analyzed the
      usefulness of a real-time polymerase chain reaction (PCR) protocol using MGB (3'
      minor groove binder) probes to detect Neisseria meningitidis in formalin-fixed
      paraffin-embedded tissues from sudden deaths where a meningococcal fulminating
      infection was suspected. The protocol included detection of meningococcal DNA
      (ctrA gene), multiplex B/C PCR serogrouping (siaD gene), and rapid confirmation
      of PCR products by microcapillary electrophoresis. Sixty-nine tissues from 15
      culture-confirmed meningococcal sudden deaths were analyzed (positive cases).
      Validation studies were performed. In each positive case, both the ctrA and the
      B/C siaD genes were detected. The ctrA was detected in 81.2% of the samples,
      whereas the serogroup (B or C) was identified in 44.9% of them. Therefore, this
      protocol may improve nonculture diagnosis and case ascertainment in meningococcal
      disease deaths, particularly when formalin-fixed tissues are the only available
      specimen.

PMID- 18068936
TI  - Five-year report of national surveillance of antimicrobial resistance in
      Pseudomonas aeruginosa isolated from non-tertiary care hospitals in Korea (2002
      2006).
AB  - A nationwide surveillance of the antimicrobial resistance of Pseudomonas
      aeruginosa isolates from non-tertiary care hospitals was conducted in Korea from
      2002 to 2006. Resistance to almost all antimicrobial agents decreased
      significantly from 2003 (P < 0.01). Resistance rates to the major antipseudomonal
      agents, ceftazidime, imipenem, meropenem, and aztreonam, were 18.8%, 20.5%,
      18.7%, and 19.7%, respectively, in 2003. However, they had all decreased to below
      10% in 2006. The proportion of multidrug-resistant isolates that were resistant
      to at least 3 of 5 major antipseudomonal agent decreased from 33.5% in 2003 to
      23.1% in 2006 (P < 0.05). In this study, we found a decreasing trend in
      resistance rates and low resistance rates in P. aeruginosa from non-tertiary care
      hospitals compared with those from general hospitals, including tertiary care
      hospitals, in Korea. Our data provide valuable information for the selection of
      reliable empiric therapies for P. aeruginosa infections in non-tertiary care
      hospital patients, including outpatients.

PMID- 18068937
TI  - Perspectives on microbial cell surface display in bioremediation.
AB  - The display of heterologous proteins on the microbial cell surface by means of
      recombinant DNA biotechnologies has emerged as a novel approach for
      bioremediation of contaminated sites. Both bacteria and yeasts have been
      investigated for this purpose. Cell surface expression of specific proteins
      allows the engineered microorganisms to transport, bio-accumulate and/or detoxify
      heavy metals as well as to degrade xenobiotics. These otherwise would not be
      taken up and transformed by the microbial cell. This review focuses on the
      application of cell surface displays for the enhanced bio-accumulation of heavy
      metals by metal binding proteins. It also reviews the biodegradation of
      xenobiotics by enzymes/proteins expressed on microbial cell surfaces.

PMID- 18068938
TI  - Comparison of individual perceptions of medication costs and benefits between
      intentional and unintentional medication non-adherence among Japanese patients.
AB  - OBJECTIVE: To identify Japanese patients' perceptions of the costs and benefits
      of their medications by administering a questionnaire validated in Western
      patients and to compare the association between the perception levels and non
      adherence to medication in the two non-adherent patient types, intentional, and
      unintentional. METHODS: Japanese patients with chronic diseases were given a
      questionnaire and interviewed, and the validity and reliability of the scales
      generated were assessed. Logistic regression was used to analyse the association
      between individual perception levels and non-adherence to the medication regimen.
      RESULTS: From 151 responses, two kinds of scales were generated following a
      report of Western patients; the necessity scale showed satisfactory reliability
      (Cronbach's alpha 0.79) but the concerns scale did not. Individual levels of
      perception of the necessity of medications were associated with unintentional non
      adherence (the higher the level, the lower the odds ratio 1.0, 0.56, 0.40, and
      0.15), while they were not associated with intentional non-adherence. CONCLUSION:
      Japanese patients' perceptions of the benefits of medications, but not the costs
      were similar to those of Western patients, and these perceptions were likely to
      be different between intentionally and unintentionally non-adherent patients.
      PRACTICE IMPLICATIONS: Strategies to improve non-adherence should be designed
      according to the non-adherent type.

PMID- 18068939
TI  - Pacific Islanders' perspectives on heart failure management.
AB  - OBJECTIVE: To identify the health beliefs, attitudes, practices, and social and
      family relations important in heart failure treatment among Pacific Islanders.
      METHODS: Four focus groups were convened with 36 Native Hawaiians and Samoans
      with heart failure and their family caregivers. Thematic data analysis was used
      to categorize data into four domains: health beliefs and attitudes, preferred
      health practices, social support systems, and barriers to heart failure care.
      RESULTS: Common coping styles and emotional experiences of heart failure in this
      population included avoidance or denial of illness, hopelessness and despair, and
      reliance on spiritual/religious beliefs as a means of support. Among study
      participants, more Samoans preferred to be treated by physicians whereas more
      Native Hawaiians preferred traditional Hawaiian methods of healing. Two types of
      social support (informational and tangible-instrumental) were identified as
      important in heart failure care. Barriers to heart failure care included poor
      knowledge of heart failure, lack of trust in physicians' care, poor physician
      patient relations, finances, dietary changes, and competing demands on time.
      CONCLUSION: The recruitment, retention, and adherence of Pacific Islanders to
      heart failure interventions is affected by an array of psychosocial and socio
      cultural factors. PRACTICE IMPLICATIONS: Interventions might be improved by
      offering participants accurate and detailed information about heart failure and
      its treatment, engaging the extended family in providing necessary supports, and
      providing tools to facilitate physician-patient relationships, among others,
      within the context of a larger socio-cultural system.

PMID- 18068940
TI  - Development and evaluation of a multimedia CD-ROM for exercise during pregnancy
      and postpartum.
AB  - OBJECTIVE: To meet the need for an interactive product on exercise during
      pregnancy and postpartum, we developed and evaluated a personally tailored
      multimedia CD-ROM. METHODS: Pregnant and postpartum women, who were randomly
      assigned to either the experimental group (PregXercise CD-ROM) or the control
      group (CD-ROM with neutral content), navigated through the CD-ROM for 1 h. Main
      outcomes were exercise self-efficacy and knowledge. RESULTS: In analyses of
      covariance, compared with the control group, the experimental group had
      significant increases in self-efficacy and knowledge. CONCLUSION: The multimedia
      CD-ROM delivering information about exercise motivation, guidelines, and
      prescription was effective in improving exercise self-efficacy and knowledge.
      PRACTICE IMPLICATIONS: Our preliminary results illustrate that healthcare
      professionals and researchers may use interactive multimedia for improving
      exercise behavior and related outcomes with pregnant and postpartum women.

PMID- 18068941
TI  - Predictors of malignant potential of cystic lesions of the pancreas.
AB  - BACKGROUND: Cystic lesions of the pancreas (CLP) are a diagnostic dilemma, the
      correct characterisation of which determines surgical management. METHODS: From
      1995 to 2005, radiology and pathology records were reviewed for the presence of
      CLP. CLP were divided into three groups; Group 1: Benign, Group 2: Pre-malignant,
      and Group 3: Malignant. RESULTS: Seventy-nine of 121 patients were included
      [Group 1: n=46, Group 2: n=10, Group 3: n=23], with a median age at diagnosis of
      68 (31-92) years. The median follow-up period was 24 (14-84) months. On
      univariate analysis, female gender (p=0.04), jaundice (p<0.01), raised serum ALT
      concentration (p=0.03), cyst size (> or = 2.5 cm) (p<0.01), and biliary duct
      dilatation (p<0.01) were associated with malignant potential. Benign cysts were
      more likely to present incidentally (p<0.01). On multi-variate analysis, cyst
      size (> or =2.5 cm) was an independent predictor of malignant potential. Sub
      group analysis revealed that cysts <2.5 cm in the head of the pancreas with
      evidence of biliary obstruction (either abnormal liver function; raised ALT
      [p=0.01], ALP [p=0.01], total bilirubin [p=0.02], and/or biliary duct dilatation
      [p<0.01]) were associated with malignant potential. CONCLUSION: Cyst size > or
      =2.5 cm on computer tomography imaging was an independent predictor of pre
      malignant and malignant pancreatic cysts. Cyst size and the presence of biliary
      obstruction predict potentially malignant cysts of the head of the pancreas,
      which require surgical management.

PMID- 18068942
TI  - [Femoral intramedullary nailing in men on fracture table: beware of the risk of
      postoperative erectile dysfunction!].

PMID- 18068943
TI  - Summer in San Diego, or failed spinal anesthesia: chemical versus technical
      phenomenon?

PMID- 18068944
TI  - [Vascular Ehlers-Danlos syndrome: a clinical syndrome to be known by every
      anaesthesiologist and intensive care physician].
AB  - We report the case of a 29-year-old female who presented with a series of major
      vascular complications in rapid succession: haemothorax following rupture of a
      mammary artery aneurysm, pulmonary embolism, anterior myocardial infarction
      secondary to spontaneous dissection of the left anterior descending artery and
      rupture of a false aneurysm of the splenic artery. A diagnosis of Ehlers-Danlos
      syndrome (vascular variant) was considered the most likely in this context.
      Characterized by an extreme vascular fragility, this rare disease poses important
      clinical management issues for the anaesthetist and intensive care physician.

PMID- 18068945
TI  - Aloin induces apoptosis in Jurkat cells.
AB  - Aloe is widely used as a dietary supplement. However, there are continuing
      concerns over the toxicity and the purity of aloe-based products. The primary
      class of compounds responsible for aloe-induced toxicity are anthraquinones. One
      of these, aloe-emodin, has been extensively investigated for apoptosis inducing
      effects. Conversely, the precursor to aloe-emodin, aloin, has been subjected to
      only minimal investigation of any cytotoxic effects. Jurkat T cells, an
      established model for the study of compound toxicity, were used to evaluate the
      effect of aloin on cell viability. Cells were analyzed using flow cytometry and
      microscopy for cell size and granularity, cell membrane integrity, mitochondrial
      membrane potential, and cell cycle profile. Treatment with aloin resulted in a
      reduction in cell size, compromised membrane integrity, and loss of mitochondrial
      membrane potential in a dose-dependent manner. Additionally, treatment with aloin
      resulted in alteration of the cell cycle, specifically a block at G2/M phase.
      Importantly, the loss of cell membrane integrity was preceded by a loss of
      mitochondrial membrane potential, suggesting a mitochondrial-dependent pathway
      for aloin-induced apoptosis. These observations provide insight into the
      potential mechanisms of aloin-induced toxicity and thus, perhaps, aloe
      preparation-induced toxicity. Furthermore, because of the concern over the safety
      of aloe-based supplements, this work suggests that aloe supplements not
      containing aloin may be safer than aloe supplements containing aloin, and that
      aloin should be considered in addition to concentrations of aloe-emodin.

PMID- 18068946
TI  - The role of thiol-reducing agents on modulation of glutamate binding induced by
      heavy metals in platelets.
AB  - In the present study, we investigated if thiol-reducing agents are capable of
      altering mercury (Hg2+), lead (Pb2+) and cadmium (Cd2+) effects on platelet
      glutamatergic system. Dimercaprol (BAL), a dithiol chelating agent
      therapeutically used for the treatment of heavy metals poisoning, was capable of
      protecting the [3H]-glutamate binding against the effects caused by Pb2+ and
      Hg2+. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), another dithiol-reducing
      chelating agent, was capable of protecting the effect caused by Cd2+, Pb2+ and
      Hg2+. The similar effect was observed with addition of dithiothreitol (DTT) on
      [3H]-glutamate binding in human platelets. Dithiol-reducing agents (BAL, DMPS and
      DTT) alone did not alter [3H]-glutamate binding. In contrast, reduced glutathione
      (GSH), a monothiol-reducing agent, caused a significant inhibition on [3H]
      glutamate binding at all concentrations tested. GSH did not modify heavy metal
      effects on [3H]-glutamate binding in platelets. The findings of the present
      investigation indicate that dithiol-reducing agents are capable of altering Hg2+,
      Pb2+ and Cd2+ effects on platelet glutamatergic system. In vitro data on
      chelating-metal interactions provide only an estimated guide to the treatment of
      heavy metal poisoning. Consequently, more studies in intoxicated patients are
      necessary to determine the precise use of the peripheral models and chelating
      agents.

PMID- 18068947
TI  - Identification of a family of SINEs and LINEs in the Pipistrellus kuhli genome: a
      new structural and functional symbiotic relationship.
AB  - We initially describe a novel tRNA-derived SINE family, abundantly and randomly
      distributed in the genome of the bat Pipistrellus kuhli. We present evidence that
      the LINE retrotransposition machinery is recruited for the creation of a new
      chimerical retrotranscript constituted by the partial LINE reverse transcriptase
      ORF2, which is interrupted by the SINE15 retrotransposon. Structural homology
      between SINE15 and Homo sapiens helix 6 7SL RNA allows us to propose multiple
      genome partners for SINE retrotransposition, such as SRP proteins and LINE
      enzymatic machinery. Moreover, on the basis of the LINE and SINE/LINE chimerical
      transcripts, we propose a mutual relationship between SINE and LINE
      retrotransposons.

PMID- 18068948
TI  - Comparing Type D personality and older age as correlates of tumor necrosis factor
      alpha dysregulation in chronic heart failure.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and its soluble receptors 1 (sTNFR1) and
      2 (sTNFR2) have been shown to be implicated in the pathogenesis of chronic heart
      failure (CHF). Ageing is accompanied by increased plasma levels of pro
      inflammatory cytokines. We hypothesized that Type D personality (joint tendency
      to experience negative emotions and to inhibit self-expression) and age may have
      similar pro-inflammatory effects in the context of CHF. Participants in this
      study were 130 consecutive outpatients with CHF (76% men); there were 70
      relatively younger (<or=59 years) and 60 relatively older (>or=60 years)
      patients. They all completed the 14-item Type D Scale (DS14); 43 patients (33%)
      had a Type D personality. A multivariate model of cytokine levels indicated an
      independent overall effect of both older age [F(1,128)=9.11, p=.003] and Type D
      personality [F(1,128)=8.28, p=.005]. Stratifying patients in age/personality
      subgroups showed that younger non-Type D patients had the lowest and older Type D
      patients the highest sTNFR1 and sTNFR2 levels (986+/-318 vs 1661+/-1128 pg/ml and
      1838+/-777 vs 2823+/-1439 pg/ml, p<.0001). Importantly, the mean sTNFR1 level in
      younger Type D patients (1359+/-660 pg/ml) was equivalent to that in older non
      Type D patients (1360+/-440 pg/ml, p=.99) who were on average 18 years older.
      Younger Type D and older non-Type D patients also had similar sTNFR2 levels
      (2406+/-1329 vs 2448+/-812 pg/ml, p=.88). Only older Type D patients had a higher
      mean TNF-alpha level as compared to patients who were younger or who were not
      Type D (5.4+/-2.9 vs 3.9+/-2.4 pg/ml, p=.008). A logistic regression model
      including sex, severity of CHF, systolic heart failure and ischemic etiology
      indicated that the combined risk category of older age or Type D was
      independently associated with substantially increased sTNFR1 and sTNFR2 levels.
      Hence, Type D personality was associated with increased TNF-alpha activity. This
      disease-promoting effect of Type D matched the pro-inflammatory effect of ageing.

PMID- 18068949
TI  - Analysis of the Rem2 - voltage dependant calcium channel beta subunit interaction
      and Rem2 interaction with phosphorylated phosphatidylinositide lipids.
AB  - Voltage dependant calcium channels (VDCC) play a critical role in coupling
      electrical excitability to important physiological events such as secretion by
      neuronal and endocrine cells. Rem2, a GTPase restricted to neuroendocrine cell
      types, regulates VDCC activity by a mechanism that involves interaction with the
      VDCC beta subunit (Ca(V)beta). Mapping studies reveal that Rem2 binds to the
      guanylate kinase domain (GK) of the Ca(V)beta subunit that also contains the high
      affinity binding site for the pore forming and voltage sensing VDCC alpha subunit
      (Ca(V)alpha) interaction domain (AID). Moreover, fine mapping indicates that Rem2
      binds to the GK domain in a region distinct from the AID interaction site, and
      competitive inhibition studies reveal that Rem2 does not disrupt Ca(V)alpha -
      Ca(V)beta binding. Instead, the Ca(V)beta subunit appears to serve a scaffolding
      function, simultaneously binding both Rem2 and AID. Previous studies have found
      that in addition to Ca(V)beta binding, Rem2 must be localized to the plasma
      membrane to inhibit VDCC function. Plasma membrane localization requires the C
      terminus of Rem2 and binding studies indicate that this domain directs
      phosphorylated phosphatidylinositide (PIP) lipids association. Plasma membrane
      localization may provide a unique point of regulation since the ability of Rem2
      to bind PIP lipids is inhibited by the phosphoserine dependant binding of 14-3-3
      proteins. Thus, in addition to Ca(V)beta binding, VDCC blockade by Rem2 is likely
      to be controlled by both the localized concentration of membrane PIP lipids and
      direct 14-3-3 binding to the Rem2 C-terminus.

PMID- 18068950
TI  - Caloric restriction and refeeding promoted different metabolic effects in fat
      depots and impaired dyslipidemic profile in rats.
AB  - OBJECTIVE: We investigated the effects of severe caloric restriction and
      refeeding with a high-fat diet on lipid uptake by visceral adipose fat and lipid
      profile in rats. METHODS: Rats were assigned to six groups: a chow diet (C), a
      high-fat diet (H), severe caloric restriction (SC and SH), and severe caloric
      restriction plus refeeding (SC-r and SH-r) during 8 wk. All animals were killed
      by decapitation 4 h after intragastric administration of [1-14C] triolein (
      approximately 0.5 g, 0.3 muCi/rat). Liver; visceral retroperitoneal (RET),
      epididymal (EPI), and omental (VIS) white adipose tissues; brown adipose tissue;
      and intestine were immediately removed and weighed. The whole intestine was
      withdrawn and homogenized to determine lipid uptake. Total cholesterol, high
      density lipoprotein (HDL), and triacylglycerol in plasma were determined
      enzymatically. RESULTS: The SC and SH groups showed reduced visceral adiposity,
      although this effect was more evident in the SC group. The SC group had greater
      lipid absorption in the VIS than the C group. The SH treatment increased RET and
      VIS lipid uptake in relation to the H group. The SH-r treatment increased RET and
      VIS adiposity. HDL cholesterol decreased with caloric restriction in the SC and
      SH groups. The SH-r treatment did not increase HDL cholesterol. CONCLUSION:
      Severe caloric restriction decreased visceral adiposity even in rats in the H
      group but did not reduce the risk of development of dyslipidemia. Therefore, food
      restriction plus refeeding with a high-fat diet increase the risk of development
      of visceral adiposity and dyslipidemia.

PMID- 18068951
TI  - Interaction of clothing and body mass index affects validity of air-displacement
      plethysmography in adults.
AB  - OBJECTIVE: We determined the effect of clothing type on the validity of air
      displacement plethysmography (ADP) to estimate percentage of body fat (%BF) and
      ascertain if these effects differ by body mass index (BMI). METHODS: The %BF by
      dual x-ray absorptiometry (DXA) and %BF, density, and body volume by ADP were
      assessed in 132 healthy adults classified by normal (N; 18.5-24.9 kg/m2),
      overweight (OW; 25-29.9 kg/m2), and obese (OB; 30-39.9 kg/m2) BMIs. RESULTS:
      Compared with DXA, ADP underestimated (P < 0.0001) %BF from scrubs (SC) and t
      shirt/shorts (TS) in N (11.4%; 8.6%) and OW (6.8%; 4.9%) BMI groups,
      respectively. ADP compared with DXA overestimated (P < 0.0006) %BF in the OW
      group (1.2%), but underestimated (P < 0.0001) it in the N group (2.4%). ADP also
      overestimated (P < 0.006) %BF in the OB group wearing spandex (SP; 4.8%), but not
      in those wearing SC (0.7%; P = 0.10) and TS (0.5%; P = 0.22) versus DXA.
      CONCLUSION: All three clothing types showed significant error in estimating %BF
      with ADP compared with DXA in N and OW BMI. Use of spandex provided the least
      error and is the preferred attire to obtain valid body composition results when
      testing N and OW subjects. However, SP provided the greatest error in the OB
      group. Error in ADP %BF in OB was minimal in SC and TS and similar to the within
      subject variability in %BF estimates with ADP. Thus, TS and SC are acceptable
      alternatives to SP in adults with excess body weight.

PMID- 18068952
TI  - Communication disturbances, working memory, and emotion in people with elevated
      disorganized schizotypy.
AB  - This study examined whether people with elevated disorganized schizotypy would
      differ from control participants on characteristics associated with
      disorganization symptoms in schizophrenia and also whether disorganized
      schizotypy was associated with problems processing emotion. People with
      disorganized schizotypy (n=32) exhibited greater communication disturbances (CD)
      than control participants (n=34) for emotionally negative topics but not for
      positive topics. In addition, the disorganized group exhibited poorer performance
      on a working memory task but not on a psychometrically matched verbal
      intelligence task. In addition, poor working memory was associated with increased
      CD for negative topics and, after controlling for group differences in working
      memory, group differences in CD were not significant. Moreover, the disorganized
      group exhibited greater emotional ambivalence and ambivalence was associated with
      increased CD in the disorganized group. These results suggest that people with
      disorganized schizotypy exhibit some similar characteristics to people with
      schizophrenia who have disorganization symptoms and that disorganized schizotypy
      is also associated with poor emotion processing.

PMID- 18068954
TI  - Amygdala responses to unattended fearful faces: Interaction between sex and trait
      anxiety.
AB  - Trait anxiety and sex have been shown to separately account for some of the
      observed individual differences in amygdala responses to emotional stimuli, but
      the combined effect of both factors remains unknown. In this fMRI study,
      participants varying in trait anxiety scores viewed a series of superimposed
      face/scene composite images (containing fearful or neutral faces) and were
      instructed to direct attention to either the face or the scene content. We
      observed an interaction between sex and trait anxiety in amygdala responses to
      fearful faces as a function of attention. In females, higher trait anxiety was
      associated with a stronger amygdala response to unattended fearful faces, whereas
      no such relationship was present in males. This observed interaction between sex
      and individual differences in trait anxiety at the level of the brain may have
      clinical implications for a better understanding of the higher incidence of
      anxiety disorders in women than men.

PMID- 18068957
TI  - Improved resolution and detection of 31P-Tl J-couplings at 21 T in 31P magic
      angle spinning NMR spectra of inorganic compounds containing Tl/Bi/P/S.
AB  - For crystalline compounds containing Tl, Bi, P, and S, greatly improved chemical
      shift resolution was observed in 31P magic angle spinning spectra obtained at 21
      T relative to spectra obtained at 9.4 T. In Hz units, the spectral linewidths
      were not strongly dependent on the applied field, which may be a result of a
      significant contribution to the linewidths from transverse relaxation. Comparison
      of the spectra at the two different fields confirmed that spectral splittings
      were due to two-bond phosphorus-thallium J-coupling. These results suggest that
      ultra-high field may be a useful tool to improve spectral resolution of spin 12
      nuclei in crystalline inorganic compounds.

PMID- 18068956
TI  - Childhood adversity predicts earlier onset of major depression but not reduced
      hippocampal volume.
AB  - Childhood adversity may influence severity and age of onset of depression,
      potentially mediated by greater vulnerability to an existing biochemical or
      neural mechanism. Prior studies have suggested that reduced hippocampal volume is
      a result of childhood adversity. This study examined the relationship between
      childhood adversity, hippocampal volumes and clinical characteristics in women
      who were recruited for depression history rather than abuse experiences. Thirty
      one women with remitted unipolar depression and 24 psychiatrically healthy women
      completed the Childhood Experience of Care and Abuse interview [Bifulco, A.,
      Brown, G.W., Harris, T.O., 1994. Childhood Experience of Care and Abuse (CECA): A
      retrospective interview measure. Journal of Child Psychology and Psychiatry 55,
      1419-1435]. High resolution MRI scans and hippocampal volumetric determination by
      stereological assessment were obtained. We found that childhood adversity was
      associated with a history of recurrent depression and with earlier age of
      depression onset. We did not find a relationship between childhood adversity and
      hippocampal volumes in this sample with mild childhood adversity. Our results
      suggest that the decreased hippocampal volume seen in Major Depressive Disorder
      may be mediated by additional factors. Further research is needed to more fully
      understand the interrelationships among childhood adversity, hippocampal
      morphology, neuroendocrine regulation, and other genetic and environmental
      factors influencing vulnerability to depression.

PMID- 18068958
TI  - Influence of assembling pH on the stability of poly(L-glutamic acid) and poly(L
      lysine) multilayers against urea treatment.
AB  - Polyelectrolyte multilayers of poly(L-glutamic acid) (PGA) and poly(L-lysine)
      (PLL) were built up using the layer-by-layer (LbL) technique in low pH (3.6,
      PM3.6) and in neutral pH (7.4, PM7.4) solutions. The multilayers were then
      treated with a concentrated urea (one kind of denaturant for proteins and
      polypeptides) solution (8M) and rinsed with corresponding buffer. The buildup and
      treatment processes were investigated by ultraviolet visible spectroscopy and
      ellipsometry. The surface morphology was observed by scanning force microscopy
      (SFM). The inner structures were determined by X-ray reflectometry and circular
      dichroism spectroscopy (CD). An exponential growth of the optical mass and the
      layer thickness was observed for both PM3.6 and PM7.4. After urea treatment, a
      significant mass loss for PM3.6 was found, while no mass change was recorded for
      PM7.4. The dominant driving force for PM7.4 is electrostatic interaction,
      resulting in multilayers with an abundant beta-sheet structure, which has higher
      stability against urea treatment. By contrast, the dominant driving force for
      PM3.6 is hydrogen bonding and hydrophobic interaction, which are sensitive to the
      urea treatment. The mechanism is substantiated by molecular mechanics
      calculation. This has offered a convenient pathway to mediate the multilayer
      properties, which is of great importance for potential applications.

PMID- 18068955
TI  - Neural bases of dysphoria in early Huntington's disease.
AB  - Psychiatric disorders, including disorders of emotion control, are common in
      Huntington's disease. The neurobiological mechanism of the increased rate of
      disorders of emotion control are not known. Emotion perception deficits have been
      reported in Huntington's disease, but studies of emotional experience have been
      limited. In the present study we aim to expand the research in emotion in
      Huntington's disease by examining the neural bases of induced dysphoria at an
      early stage of Huntington's disease. Ten Huntington's disease patients and 12
      demographically matched healthy volunteers underwent [(15)O] water positron
      emission tomography while in a transient state of dysphoria induced by viewing
      negatively charged affect-laden stimuli. Both groups experienced dysphoric mood,
      but Huntington's disease patients responded to the stimuli with greater arousal,
      anger and fear than healthy controls. Induced dysphoric mood was associated with
      a widespread reduction of activity within the frontal and parietal lobes,
      thalamus, and cerebellum. These differences could not be explained based on the
      smaller gray matter volumes of the corresponding regions, although in
      Huntington's disease patients smaller caudate nucleus volumes predicted lower
      dorsal-lateral prefrontal activity. Areas of increased activity included the
      striate and extrastriate cortex, the left thalamus, the transverse temporal
      gyrus, and the posterior hippocampus. This study elucidates possible mechanisms
      contributing to psychiatric disturbances of emotion often found in patients with
      Huntington's disease.

PMID- 18068959
TI  - Phosvitin-calcium aggregation and organization at the air-water interface.
AB  - Phosvitin, an egg yolk protein constituted by 50% of phosphorylated serines,
      presents good emulsifying properties whereas its interfacial properties are not
      yet clearly elucidated and remain object of discussion. Phosvitin has a high
      charge density and naturally forms aggregates through phosphocalcic bridges in
      egg yolk. This high charge density, doubled by this capacity to aggregate, limits
      the adsorption of the protein at the air-water interface. In this work, we
      investigated the aggregation impact by calcium ions on the organization of the
      phosvitin interfacial film using the atomic force microscopy. Phosvitin
      interfacial films without calcium ions are compared to phosvitin interfacial
      films formed in the presence of calcium ions in the subphase. We demonstrated
      that phosvitin is able to anchor at air-water interfaces in spite of its numerous
      negative charges. In the compression isotherm a transition was observed just
      before 28 mN/m signifying a possible modification of the interfacial film
      structure or organization. Calcium ions induce a reorganization towards a greater
      compaction of the phosvitin interfacial film even at low surface pressure. In
      conclusion we suggest that, in diluted regime, phosvitin molecules could adsorb
      by their two hydrophobic extremities exhibiting loops in the aqueous phase,
      whereas in concentred regime (high interfacial concentration) it would be
      adsorbed at the interface by only one extremity (brush model).

PMID- 18068960
TI  - The Frank Ellis memorial lecture: the use of three-dimensional imaging in
      gynaecological radiation therapy.
AB  - The use of three-dimensional image guidance in radiation therapy has increased
      dramatically over the past decade. In gynaecological malignancies, three
      dimensional image guidance assists with both external beam and brachytherapy
      treatment planning, increasing the accuracy of dose delivery. During his
      lifetime, Frank Ellis made significant contributions to gynaecological
      brachytherapy. This lecture will focus on novel advances in three-dimensional
      image-guided radiation therapy for cervical cancer, with the ultimate goal of
      improving outcomes for our patients.

PMID- 18068961
TI  - A prospective study of determinants of the metabolic syndrome in adults.
AB  - BACKGROUND AND AIM: Few studies have prospectively examined the development of
      the metabolic syndrome and comprehensive set of risk factors in a cohort. The
      objective of this study was to evaluate determinants of the metabolic syndrome in
      adults in a prospective study. METHODS AND RESULTS: In this population-based
      cohort study, a representative sample of 410 subjects (184 men and 226 women),
      aged 18-74 years, free of the metabolic syndrome at baseline, were studied. In
      the subsequent 3.5 years metabolic syndrome, defined according to ATP III
      guidelines, developed in 71 subjects (33 men and 38 women) The best determinants
      of metabolic syndrome were hypertension [odds ratio (OR) by quartiles: 1, 1.2,
      1.6, 4.2, p for trend <0.05], waist circumference (1, 1.1, 2, 5.3, p for trend
      <0.05), triglyceride (1, 1, 2, 3, p for trend <0.05) and HDL cholesterol (1, 0.4,
      0.4, 0.3, p for trend <0.05). A prominent dose-response relationship across the
      carbohydrate and fat intake categories and the odds of metabolic syndrome was
      observed in univariate analysis. In multivariate analysis high waist
      circumference was the optimum predictor [OR 8 (4-12.2)]. CONCLUSION: This report
      confirms importance of blood pressure, waist circumference and lipid measurements
      in risk stratification of metabolic syndrome in adulthood. Interventions that
      address obesity and reduce waist circumference and an appropriate diet may reduce
      the incidence of the metabolic syndrome in adults.

PMID- 18068962
TI  - Guatemalan plants extracts as virucides against HIV-1 infection.
AB  - Prevention methods to avoid transmission of pathogens, including HIV, are crucial
      in the control of infectious diseases, not only to block epidemic spread but to
      avoid long-term treatments leading to emergence of resistances and drug
      associated side effects. Together with vaccine development, the discovery of new
      virucidal agents represents a research priority in this setting. In the screening
      of new compounds with antiviral activity, three Guatemalan plant extracts from
      Justicia reptans, Neurolaena lobata and Pouteria viridis were evaluated with a
      classic antiviral assay and were found to inhibit HIV replication. This activity
      was corroborated by an original recombinant virus assay, leading us to perform a
      deeper study of the virucidal activity. Active fractions were non-toxic in vitro
      and also inhibited other enveloped viruses. Moreover, these fractions were able
      to inhibit the transfer of HIV from dendritic cells (DCs) to lymphocytes, that
      represents the main way of HIV spread in vivo.

PMID- 18068963
TI  - Comparative in vitro study on the anti-herpetic effect of phytochemically
      characterized aqueous and ethanolic extracts of Salvia officinalis grown at two
      different locations.
AB  - Aqueous and ethanolic extracts of Salvia officinalis (Lamiaceae) from two
      different locations (Garden and Swabian Mountains) were examined in vitro on RC
      37 cells for their antiviral activity against herpes simplex virus type 1 (HSV-1)
      and type 2 (HSV-2) using a plaque reduction assay. The 50% inhibitory
      concentrations (IC50) of the extracts for HSV plaque formation were determined in
      dose-response studies. All extracts tested revealed a high virucidal activity
      against free HSV-1 and HSV-2. The experimental data exhibited a significant
      higher sensitivity of HSV against the extracts derived from Garden in comparison
      with those from Swabian Mountains. The most active one was the Garden 20% ethanol
      extract with IC50 values of 0.18 microg/ml for HSV-1 and 0.04 microg/ml for HSV
      2. In order to identify the mode of antiviral action, the extracts were added to
      the host cells (RC-37) or viruses at different stages of infection. Independently
      of the location, both types of herpes viruses were considerably inactivated after
      treatment with the extracts prior to cell infection. Plaque formation was
      significantly reduced by >90% for HSV-1 and by >99% for HSV-2. Pretreatment of
      the host cells with both Garden and Swabian Mountains 20% and 40% ethanolic
      extracts prior to virus infection revealed a strong reduction of HSV-2 plaque
      formation by 94% and 70% (Garden) and 99% and 45% (Swabian Mountains),
      respectively. In time-activity studies with free HSV-1 over a period of 2h, a
      clearly time-dependent activity was demonstrated whereby the ethanolic extracts
      of both locations revealed a much higher activity than the aqueous ones. The 20%
      ethanolic extracts of both locations are of special interest and were effective
      when added to host cells and free virus. A topical application with a dual mode
      of action would be ideal against recurrent herpes infections.

PMID- 18068964
TI  - Changes in antioxidant defense status in hypercholesterolemic rats treated with
      Ajuga iva.
AB  - The aim of the study was to investigate the effect of aqueous extract of Ajuga
      iva (Ai) on serum and tissues lipid peroxidation as well as antioxidant enzymes
      activities in red blood cells (RBC) and tissues, in high hypercholesterolemic
      rats (HC). Male Wistar rats (n=12) were fed on 1% cholesterol-enriched diet for
      15d. After this adaptation phase, hypercholesterolemic rats (total
      cholesterol=6.5+/-0.6mol/l) were divided into two groups fed the same diet and
      treated or not with Ai for 15d. Thiobarbituric acid reactive substances (TBARS)
      concentrations in serum, LDL-HDL(1), HDL(2) and HDL(3) were respectively, 5-, 7.8
      , 2.3- and 5-fold lower in Ai treated than untreated hypercholesterolemic groups.
      TBARS concentrations were 1.4-fold lower in heart and 2.8-fold higher in kidney
      in Ai-HC treated than untreated HC group. Superoxide dismutase activity was
      respectively, 1.2- and 1.4-fold higher in RBC and muscle in Ai treated than
      untreated group. In RBC, Ajuga iva treatment enhanced glutathione peroxidase (GSH
      Px) (+9%) and glutathione reductase (GSSH-Red) (+12%) in Ai-HC treated than
      untreated HC group. GSSH-Red activity was 1.4- and 1.5-fold higher in adipose
      tissue and heart, respectively and 3.7-fold lower in kidney in Ai treated than
      untreated group. Liver catalase activity was 1.6-fold higher in Ai treated than
      untreated group. Adipose tissue and muscle total glutathione content represented
      in Ai treated group 35% and 36% of the value noted in untreated group. Nitric
      oxide values of liver, adipose tissue and heart were 3.3-, 2.5- and 3.4-fold
      higher in Ai-HC than HC group. Ajuga iva treatment enhanced alpha-tocopherol
      contents (+25%) in Ai treated than untreated group. In conclusion, Ajuga iva
      treatment is more effective to improve the antioxidant capacity of RBC than that
      of tissues. Indeed, Ai is able to reduce the oxidative stress in
      hypercholesterolemic rats by increasing the antioxidant enzymes activity.

PMID- 18068965
TI  - Cytotoxic properties of thiophenes from Echinops grijissi Hance.
AB  - The dichloromethane fraction of the crude ethanol extract of Echinops grijissi
      Hance roots exhibited different cytotoxicity against a panel of four human tumor
      cell lines, HepG2, K562, HL60 and MCF-7. By a bioassay-guided fractionation,
      eight thiophenes were isolated from the dichloromethane fraction, one of them was
      isolated from the plant for the first time. And they were assayed for their
      toxicity against the cell lines in order to compare their relative anti-tumor
      activity and find candidates of potential anti-tumor drugs. The dichloromethane
      fraction and isolated thiophenes showed different activity against the cell
      lines, and the anti-tumor activity of the dichloromethane fraction was also
      studied in vivo in S180 implanted ICR mice, however, it exhibited no anti-tumor
      activity at dosage of 20 or 40 mg/kg/d. There were also deaths recorded and the
      animals showed signs of toxicity when the dosage is 200 mg/kg/d.

PMID- 18068966
TI  - The hormonal effects of Tribulus terrestris and its role in the management of
      male erectile dysfunction--an evaluation using primates, rabbit and rat.
AB  - Hormonal effects of Tribulus terrestris (TT) were evaluated in primates, rabbit
      and rat to identify its usefulness in the management of erectile dysfunction
      (ED). TT extract was administered intravenously, as a bolus dose of 7.5, 15 and
      30 mg/kg, in primates for acute study. Rabbits and normal rats were treated with
      2.5, 5 and 10mg/kg of TT extract orally for 8 weeks, for chronic study. In
      addition, castrated rats were treated either with testosterone cypionate
      (10mg/kg, subcutaneously; biweekly for 8 weeks) or TT orally (5mg/kg daily for 8
      weeks). Blood samples were analyzed for testosterone (T), dihydrotestosterone
      (DHT) and dehydroepiandrosterone sulphate (DHEAS) levels using radioimmunoassay.
      In primates, the increases in T (52%), DHT (31%) and DHEAS (29%) at 7.5mg/kg were
      statistically significant. In rabbits, both T and DHT were increased compared to
      control, however, only the increases in DHT (by 30% and 32% at 5 and 10mg/kg)
      were statistically significant. In castrated rats, increases in T levels by 51%
      and 25% were observed with T and TT extract respectively that were statistically
      significant. TT increases some of the sex hormones, possibly due to the presence
      of protodioscin in the extract. TT may be useful in mild to moderate cases of ED.

PMID- 18068968
TI  - Women, harm reduction and history: gender perspectives on the emergence of the
      'British System' of drug control.
AB  - Taking Kohn's classic book Dope Girls as its starting point, this paper explores
      the particular place of women and gender issues in the emergence of the 'British
      System' of drug control in the early twentieth century. The 'British System'
      refers to the approach put in place in the 1920s in Britain, notably by the 1926
      Rolleston Report. In essence, it involved the medically based prescription of
      opiates to addicts, often on a long-term basis. It is viewed by many as one of
      the beginnings of the general principle of harm reduction within drug policy.
      This paper will examine how female figures - chorus girls, actresses, night club
      girls, prostitutes - were central to British drugs discourse in the 1920s, with
      the representation of some individual women in particular, most famously the
      actress Billie Carleton, featuring very prominently. It will be argued that this
      gendering of drugs discourse can be best understood in the wider context of
      social change, namely the transition from liberalism to welfarism at the turn of
      the twentieth century. It is suggested that this historical analysis provides a
      radical new perspective on some fundamental issues for contemporary approaches to
      harm reduction for women, a perspective that has far-reaching implications and
      challenges some 'taken-for-granted' assumptions.

PMID- 18068967
TI  - Understanding recreational ecstasy use in the United States: a qualitative
      inquiry.
AB  - BACKGROUND: Ecstasy use has increasingly become popular among young adults, many
      of whom view it as a safe drug with no or limited negative social and health
      consequences. In this paper, we explore the perceptions of ecstasy users about
      its recreational use as well as regarding the normalisation of use. METHODS: The
      study participants were recruited using targeted and theoretical sampling. To be
      eligible, they had to be between 18 and 25 years and have used ecstasy at least
      four times within the past 90 days. In-depth interviews were conducted with 112
      individuals. Data analysis included the constant comparison method commonly used
      in modified grounded theory. RESULTS: The study participants associated their
      recreational ecstasy use with control, shaping both the timing and setting of
      their use. In addition, they supported that easy access/availability and social
      accommodations of use contributed to their acceptance of ecstasy use as a normal
      part of life. Moreover, low risk perceptions of the social and health
      consequences of ecstasy used were identified as resulting in normalisation.
      CONCLUSION: The study findings reveal the importance of considering recreational
      ecstasy use from the perspective of the users themselves for prevention efforts
      and when providing social and health services, including intervention strategies.
      In addition, the potential normalisation of ecstasy use must be considered.

PMID- 18068969
TI  - Increased sustainable electricity generation in up-flow air-cathode microbial
      fuel cells.
AB  - Sustainable electricity was generated from glucose in up-flow air-cathode
      microbial fuel cells (MFCs) with carbon cloth cathode and carbon granular anode.
      Plastic sieves rather than membrane were used to separate the anode and cathode.
      Based on 1g/l glucose as substrate, a maximum volumetric power density of 25+/-4
      W/m(3) (89 A/m(3)) was obtained for the MFC with a sieve area of 30 cm(2) and
      49+/-3 W/m(3) (215 A/m(3)) for the MFC with a sieve area of 60 cm(2). The
      increased power density with larger sieve area was mainly due to the decrease of
      internal resistance according to the electrochemistry impedance spectroscopy
      analysis. Increasing the sieve area from 30 cm(2) to 60 cm(2) resulted in a
      decrease of overall internal resistance from 41 ohm to 27.5 ohm and a decrease of
      ohmic resistance from 24.3 ohm to 14 ohm. While increasing operational
      recirculation ratio (RR) decreased internal resistance and increased power output
      at low substrate concentration, the effect of RR on cell performance was
      negligible at higher substrate concentration.

PMID- 18068970
TI  - Specific and selective probes for Pseudomonas aeruginosa from phage-displayed
      random peptide libraries.
AB  - The design of novel biosensors for the detection of biological threats, such as
      Pseudomonas aeruginosa, requires probes that specifically bind biological agents
      and insure their immediate and efficient recognition. Advanced bio-selective
      sensors may meet the requests for isolation, concentration of the agents and
      their real-time detection. There is a need for robust and inexpensive affinity
      probes alternative to antibodies. These probes may be recruited from random
      peptide libraries displayed on filamentous phage. In this study, we identified
      from two phage-displayed random peptide libraries phage clones displaying
      peptides capable of specific and strong binding to P. aeruginosa cell surface.
      The ability of the phage clones to interact specifically with P. aeruginosa was
      demonstrated by using enzyme-linked immunosorbent assay (ELISA). We assessed
      selectivity of phage-bacteria-binding by comparing the binding ability of the
      selected clones to the selector bacterium and a panel of other bacterial species;
      we also demonstrated by dot spot and immunoblotting that the most reactive and
      selective phage peptide bound with high avidity the bacterial cell surface. In
      addition, as proof-of-concept, we tested the possibility to immobilize the
      affinity-selected phage to a putative biosensor surface. The quality of phage
      deposition was monitored by ELISA, and phage-bacterial-binding was confirmed by
      high-power optical phase contrast microscopy. Overall, the results of this work
      validate the concept of affinity-selected recombinant filamentous phages as
      probes for detecting and monitoring bacterial agents under any conditions that
      warrant their recognition, including clinical-based diagnostics and possibly
      biological warfare applications.

PMID- 18068971
TI  - Channel-resolved multianalyte immunosensing system for flow-through
      chemiluminescent detection of alpha-fetoprotein and carcinoembryonic antigen.
AB  - A novel flow-through immunosensing system for chemiluminescent (CL) multianalyte
      immunoassay was designed based on channel-resolved technique. Using alpha
      fetoprotein (AFP) and carcinoembryonic antigen (CEA) as model analytes, two
      polyethersulfone membranes modified with the corresponding capture antibodies
      were set in two channels of a flow cell, and then two mixtures of the sample and
      corresponding alkaline phosphatase labeled antibodies were introduced into the
      channels for on-line incubation, respectively. Upon injection of CL substrate the
      catalyzed CL signals from the two channels were sequentially collected with the
      aid of an optical shutter for CL detection of two analytes. The antibodies
      immobilized membranes could be regenerated for reuse. Under optimal conditions
      AFP and CEA could be assayed in the ranges of 5.0-150 and 0.50-80 ng/ml with
      detection limits of 1.5 and 0.25 ng/ml, respectively. The assay results of
      clinical serum samples with the proposed system were in acceptable agreement with
      those with the reference method in single-analyte test mode. This novel
      immunosensing system based on the designed channel-resolved technique provided an
      automated, reusable, simple, sensitive and low-cost approach for multianalyte
      immunoassay without using of expensive array detector.

PMID- 18068972
TI  - Microarray based Raman spectroscopic detection with gold nanoparticle probes.
AB  - A microarray approach based on surface-enhanced Raman spectroscopic (SERS) was
      developed for detection of spotted peptide, peptide-protein or protein-antibody
      interaction. The procedure involves the attachment of peptide-capped gold
      nanoparticles followed by silver deposition for signal enhancement. The
      attachment of the gold nanoparticles is achieved by standard avidin-biotin
      chemistry. The well-known biomolecular recognition pairs, IgG/protein A and
      biotin/avidin, were used to demonstrate proof-of-concept of the SERS assay.
      Detection limits of 10 and 100 fg per microarray spot were obtained respectively
      for the peptide and protein arrays. For the protein in solution, a limit of 0.1
      microg/mL is reported. Furthermore, enzyme activity of the kinase (PKA) is also
      detected with high specificity for an established peptide substrate (kemptide) on
      the microarray spots.

PMID- 18068973
TI  - Pyrolysis of safflower (Charthamus tinctorius L.) seed press cake: part 1. The
      effects of pyrolysis parameters on the product yields.
AB  - Safflower (Charthamus tinctorius L.) seed press cake was pyrolysed in a fixed-bed
      reactor. The effects of pyrolysis temperature, heating rate and sweep gas flow
      rates on the yields of the products were investigated. Pyrolysis runs were
      performed using pyrolysis temperatures between 400 and 600 degrees C with heating
      rates of 10, 30 and 50 degrees C min(-1). The obtained bio-char, gas and bio-oil
      yields ranged between 25 and 34 wt%, 19 and 25 wt%, and 28 and 36 wt%,
      respectively, at different pyrolysis conditions. The highest liquid yield was
      obtained at 500 degrees C pyrolysis temperature with a heating rate of 50 degrees
      C min(-1) under the sweep gas of N(2) with a flow rate of 100 cm(3)min(-1).
      Employing the higher heating rate of 50 degrees C min(-1) results in maximum bio
      oil yield, probably due to the decrease in mass transfer limitations. According
      to the results obtained under the conditions of this study, the effects of
      pyrolysis temperature and sweep gas flow rate are more significant than the
      effect of heating rate on the yields.

PMID- 18068974
TI  - Purification and characterization of xylanase from Aspergillus ficuum AF-98.
AB  - The purification and characterization of xylanase from Aspergillus ficuum AF-98
      were investigated in this work. The extracellular xylanase from this fungal was
      purified 32.6-fold to homogeneity throughout the precipitation with 50-80%
      (NH(4))(2)SO(4), DEAE-Sephadex A-50 ion exchange chromatography and Sephadex G
      100 chromatography. The purified xylanase (specific activity at 288.7 U/ mg
      protein) was a monomeric protein with a molecular mass of 35.0 kDa as determined
      by SDS-PAGE. The optimal temperature and pH for the action of the enzyme were at
      45 degrees C and 5.0, respectively. The xylanase was activated by Cu(2+) up to
      115.8% of activity, and was strongly inhibited by Hg(2+), Pb(2+) up to 52.8% and
      89%, respectively. The xylanase exhibited K(m) and V(max) values of 3.267 mg/mL,
      18.38 M/min/mg for beechwood xylan and 3.747 mg/mL, 11.1M/min/mg for birchwood
      xylan, respectively.

PMID- 18068975
TI  - Design, synthesis, and biological evaluation of human sialidase inhibitors. Part
      1: selective inhibitors of lysosomal sialidase (NEU1).
AB  - We here report the design and synthesis of selective human lysosomal sialidase
      (NEU1) inhibitors. A series of amide-linked C9 modified DANA (2-deoxy-2,3-dehydro
      N-acetylneuraminic acid) analogues were synthesized and their inhibitory
      activities against all four human sialidases (NEU1-NEU4) were determined.
      Structure-based approach was used to investigate the basis of selectivity of the
      compounds with experimentally observed activity. Results from the present study
      are found to be informative in a qualitative manner for the further design of
      isoform selective human sialidase inhibitors for therapeutic value.

PMID- 18068976
TI  - Conversion of an MMP-potent scaffold to an MMP-selective HER-2 sheddase inhibitor
      via scaffold hybridization and subtle P1' permutations.
AB  - A series of beta-sulfonamide piperidine hydroxamates were prepared and shown to
      be potent inhibitors of the human epidermal growth factor receptor-2 (HER-2)
      sheddase with excellent selectivity against MMP-1, -2, -3, and -9. This was
      achieved by exploiting subtle differences within the otherwise highly conserved
      S(1)(') binding pocket of the active sites within the metalloprotease family. In
      addition, it was discovered that the introduction of polarity to the P(1) and
      P(1)(') groups reduced the projected human clearance.

PMID- 18068977
TI  - Inhibition of dipeptidyl peptidase-IV (DPP-IV) by atorvastatin.
AB  - Dipeptidyl peptidase-IV (DPP-IV) is an enzyme responsible for the inactivation of
      the glucoregulatory incretin hormones glucagon-like peptide-1 (GLP-1) and glucose
      dependent insulinotropic polypeptide (GIP). In this report, we show that the
      hypolipidemic agent atorvastatin is a competitive inhibitor of porcine DPP-IV in
      vitro, with K(i)=57.8+/-2.3 microM. These results may have implications in the
      development of novel DPP-IV inhibitors based on the use of atorvastatin as a lead
      compound for the treatment of type 2 diabetes.

PMID- 18068978
TI  - New insights into the first oxidative phenol coupling reaction during vancomycin
      biosynthesis.
AB  - OxyB catalyzes the first oxidative phenol coupling reaction in vancomycin
      biosynthesis. OxyB is a P450 hemoprotein whose activity is strictly dependent
      upon the presence of molecular oxygen. Here, it was shown that label from
      (18)O(2) is not incorporated into the monocyclic product during catalysis by
      OxyB. In addition, it was shown that OxyB can convert a model hexapeptide
      substrate containing (R)-Tyr6, instead of (S)-Tyr6, covalently linked as a C
      terminal thioester to a peptidyl carrier protein (PCP-7S) derived from the
      vancomycin non-ribosomal peptide synthetase (NRPS), into the corresponding
      epimeric monocyclic product. The binding of this epimeric hexapeptide-PCP
      conjugate to the Fe(III) form of OxyB, as monitored by UV-vis spectroscopy,
      revealed a K(d)=35+/-5 microM. Thus, the enzyme reveals a surprising lack of
      stereospecificity in the binding and transformation of these epimeric substrates.

PMID- 18068979
TI  - Novel ofloxacin derivatives: synthesis, antimycobacterial and toxicological
      evaluation.
AB  - Thirty novel 9-fluoro-2,3-dihydro-8,10-(mono/di-sub)-3-methyl-8-nitro-7-oxo-7H
      [1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acids were synthesized from 2,3,4,5
      tetrafluoro benzoic acid and evaluated for in vitro and in vivo antimycobacterial
      activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant
      Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC(2)) and also
      tested for the ability to inhibit the supercoiling activity of DNA gyrase from
      mycobacteria. Among the synthesized compounds, 10-[2-carboxy-5,6
      dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7
      oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most
      active compound in vitro with MIC99 of 0.19 microM and 0.09 microM against MTB
      and MTR-TB, respectively. In the in vivo animal model also the same compound
      decreased the bacterial load in lung and spleen tissues with 1.91 and 2.91--log10
      protections, respectively, at the dose of 50mg/kg body weight. Compound 10-[(4
      ((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)]-9-fluoro-2,3-dihydro-3-methyl-8
      nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be
      the most active in the inhibition of the supercoiling activity of DNA gyrase with
      an IC(50) of 10.0 microg/mL. The results demonstrate the potential and importance
      of developing new oxazino quinolone derivatives against mycobacterial infections.

PMID- 18068980
TI  - Synthesis of genistein derivatives and determination of their protective effects
      against vascular endothelial cell damages caused by hydrogen peroxide.
AB  - A series of genistein derivatives, prepared by alkylation and
      difluoromethylation, were tested for their inhibitory effects on the hydrogen
      peroxide induced impairment in human umbilical vein endothelial (HUVE-12) cells
      in vitro. The HUVE-12 cells were pretreated with either the vehicle solvent
      (DMSO), genistein, or different amounts of the genistein derivatives for 30 min
      before exposed to 1 mM hydrogen peroxide for 24 h. Cell apoptosis was determined
      by flow cytometry with propidium iodide (PI) staining. Cellular injury was
      estimated by measuring the lactate dehydrogenase (LDH) release. Data suggested
      that the genistein derivatives possessed a protective effect on HUVE-12 cells
      from hydrogen peroxide induced apoptosis and reduced LDH release. Among these
      derivatives, 7-difluoromethyl-5,4'-dimethoxygenistein exhibited the strongest
      activity against hydrogen peroxide induced apoptosis of HUVE-12 cells.

PMID- 18068981
TI  - A set of phosphatase-inert "molecular rulers" to probe for bivalent mannose 6
      phosphate ligand-receptor interactions.
AB  - A set of bivalent mannose 6-phosphonate 'molecular rulers' has been synthesized
      to examine ligand binding to the M6P/IGF2R. The set is estimated to span a P-P
      distance range of 16-26A (MMFF energy minimization on the hydrated phosphonates).
      Key synthetic transformations include sugar triflate displacement for phosphonate
      installation and Grubbs I cross-metathesis to achieve bivalency. Relative binding
      affinities were tested by radioligand displacement assays versus PMP-BSA
      (pentamannosyl phosphate-bovine serum albumin). These compounds exhibit slightly
      higher binding affinities for the receptor (IC(50)'s=3.7-5 microM) than the
      parent, monomeric mannose 6-phosphonate ligand and M6P itself (IC(50)=11.5+/-2.5
      microM). These results suggest that the use of an alpha-configured anomeric
      alkane tether is acceptable, as no significant thermodynamic penalty is
      apparently paid with this design. On the other hand, the modest gains in binding
      affinity observed suggest that this ligand set has not yet found true bivalent
      interaction with the M6P/IGF2R (i.e., simultaneous binding to two distinct M6P
      binding pockets).

PMID- 18068982
TI  - Design and synthesis of novel potent and selective integrin alphanubeta3
      antagonists--novel synthetic routes to isoquinolinone, benzoxazinone, and
      quinazolinone acetates.
AB  - An unexpected ring contraction of benzazepinone based alpha(nu)beta(3)
      antagonists led to the design of quinolinone-type derivatives. Novel and
      efficient synthetic routes to isoquinolinone, benzoxazinone, and quinazolinone
      acetates were established. Nanomolar alpha(nu)beta(3) antagonists based on these
      new scaffolds were prepared. Moreover, benzoxazinones 15a and 15b exhibited high
      microsomal stability and good permeability.

PMID- 18068983
TI  - Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring
      substituents extending into the S1' substrate binding pocket.
AB  - The proteolytic enzyme beta-secretase (BACE-1) produces amyloid beta (Abeta)
      peptide, the primary constituent of neurofibrillary plaques, implicated in
      Alzheimer's disease, by cleavage of the amyloid precursor protein. A small
      molecule inhibitor of BACE-1, (diaminomethylene)-2,5-diphenyl-1H-pyrrole-1
      acetamide (1, BACE-1 IC(50)=3.7 microM), was recently described, representing a
      new small molecule lead. Initial SAR investigation demonstrated the potential of
      accessing the nearby S(3) and S(1)(') substrate binding pockets of the BACE-1
      enzyme by building substituents off one of the phenyl substituents and guanidinyl
      functional group. We report here the optimization of guanidinyl functional group
      substituents on 1, leading to potent submicromolar BACE-1 inhibitors.

PMID- 18068984
TI  - The direct route: a simplified pathway for protein import into the mitochondrion
      of trypanosomes.
AB  - Trypanosoma brucei is a unicellular eukaryote that causes the deadly human
      African trypanosomiasis ('sleeping sickness') in humans. The parasite has a
      complicated lifestyle, it developmentally changes aspects of its mitochondrial
      function as it alternates from forms in the tsetse fly to forms adapted for life
      in the human bloodstream. The single mitochondrion found in each trypanosome has
      to be duplicated precisely in each round of the cell cycle in order for parasites
      to replicate, and this depends on the import of proteins from the cytosol. Here
      we review what is known about the mitochondrial protein import pathway in T.
      brucei, how it compares with the process in humans, and how the distinguishing
      features seen in T. brucei and humans promise new understanding of the
      mitochondrial protein import process in all eukaryotes.

PMID- 18068985
TI  - Flexion-distraction injury of the L1 vertebra treated with short-segment
      posterior fixation and Optimesh.
AB  - We report a patient with a flexion-distraction injury of the L1 vertebra treated
      with a combination of short-segment posterior fixation and Optimesh (Spineology
      Inc., St. Paul, MN, USA), a flexible balloon-shaped mesh that is deployed into
      the fractured vertebra together with allograft. The patient, a 47-year-old man,
      was admitted after sustaining a motor vehicle accident. Imaging studies showed an
      L1 compression fracture. The patient had no neurologic deficits and was treated
      conservatively. However, intense back pain persisted and significant kyphosis was
      noted when he mobilized. Review of the imaging studies strongly suggested
      disruption of the posterior spinal ligaments. Surgical intervention was performed
      to address both restoration of the posterior tension band and anterior column
      height simultaneously. The combined procedure consisted of short-segment
      posterior fixation from T12 to L2, and placement of Optimesh filled with
      allograft into the L1 vertebral body. The anterior column height was restored and
      spinal alignment was corrected by the procedure, and the patient's back pain
      subsided soon after the procedure. The role of minimally invasive procedures for
      reconstruction of the vertebral column height, including the Optimesh system, in
      patients with thoracolumbar compression fracture seems promising. However, the
      long-term efficacy of these new techniques is unknown. It also remains to be seen
      how the delivery of allograft into the fractured vertebra via Optimesh affects
      remodeling, and whether the restored vertebral height is maintained.

PMID- 18068986
TI  - Cardio-embolic cerebellar stroke secondary to mitral valve chordae rupture as a
      delayed complication of a high-voltage electrical injury.
AB  - A 41-year-old farmer sustained a high-voltage electrical injury resulting in
      confusion, electrical burns and paroxysmal atrial fibrillation which
      spontaneously reverted to sinus rhythm after a few hours. Two weeks later he
      presented with a sudden onset of headache, unsteadiness, horizontal oscillopsia
      and paraesthesia in the right side of his face. Examination revealed nystagmus to
      the right, right-sided limb ataxia and a tendency to veer toward the right when
      walking. An MRI of the brain demonstrated an acute infarct of the right
      cerebellar hemisphere in the territory of the right posterior inferior cerebellar
      artery. A transesophageal echocardiogram showed a ruptured mitral valve chordae.
      This is the first report of a cardio-embolic stroke secondary to mitral valve
      chordae rupture as a delayed complication of high-voltage electrical injury.
      Although many mechanisms of direct cerebral electrical injury have been
      speculated, a cardio-embolic origin should not be overlooked as a cause of stroke
      secondary to high-voltage electrical injury.

PMID- 18068987
TI  - Validation of linear cerebral atrophy markers in multiple sclerosis.
AB  - Linear measures of cerebral ventricular enlargement may act as surrogate measures
      of cerebral atrophy in multiple sclerosis (MS). Linear atrophy markers were
      measured from routine MRI scans during a population survey of 171 Tasmanian MS
      patients and 91 healthy controls. Thirty-five Victorian MS clinic patients were
      recruited as a validation cohort with 14 of these re-assessed 4 years later. In
      the population survey, we measured three linear brain atrophy markers: inter
      caudate distance (ICD), third ventricle width (TVW) and frontal horn width (FHW).
      TVW (OR 2.0, p=0.001) and ICD (OR 16.1, p<0.001) differentiated between MS cases
      and controls. In the validation study, we correlated the intercaudate ratio
      (ICR=ICD/brain width) and third ventricular ratio (TVR=TVW/brain width) with
      brain parenchymal volume. Cross-sectionally, ICR (R=-0.453, p<0.01) and TVR (R=
      0.653, p<0.01) were correlated with brain parenchymal volume. Longitudinally,
      brain parenchymal volume loss was inversely correlated with increased ICD (R=
      0.77, p<0.01) and TVW (R=-0.71, p<0.01). This study shows that ICD measurements
      obtained from clinical MRI scans are valid brain atrophy measures for use in
      monitoring MS progression.

PMID- 18068988
TI  - Meningeal extramedullary haematopoiesis mimicking subdural hematoma.
AB  - Extramedullary haematopoiesis is a compensatory phenomenon in diseases where
      erythrocyte production is diminished or destruction is accelerated. The authors
      describe a rare case of meningeal extramedullary haematopoiesis mimicking
      subdural hematoma. CT scan revealed a hyperdense subdural lesion at the right
      frontal region following head injury. The patient was operated on and the
      pathological examination of the subdural lesion showed extramedullary
      haematopoiesis.

PMID- 18068989
TI  - Radiation-induced optic neuropathy.
AB  - Radiation-induced optic neuropathy (RION) is a devastating late complication of
      radiotherapy to the anterior visual pathway resulting in acute, profound,
      irreversible visual loss. It is thought to be a result of radiation necrosis of
      the anterior visual pathway. Visual loss may be unilateral or bilateral;
      simultaneous or sequential. RION occurs commonly between 10-20 months, with an
      average of 18 months after treatment; but the onset may range from three months
      to 9 years. Cumulative doses of radiation that exceed 50 Gy or single doses to
      the anterior visual pathway or greater than 10 Gy are usually required for RION
      to develop. Several factors are associated with a higher risk for developing RION
      or for RION occurring with lower total doses of radiation. These include age, pre
      existing compression of the optic nerve and chiasm by tumour, concurrent
      chemotherapy or previous external beam radiation. MRI, the investigation of
      choice for identifying radiation injury to the visual pathway, may show
      abnormalities before the loss of vision. Typically, the unenhanced T1- and T2
      weighted images show no abnormality, but the optic nerve will show enhancement on
      T1-weighted images with MRI. Treatment with systemic corticosteroids,
      anticoagulation and hyperbaric oxygen has been generally unsuccessful and
      disappointing. If visual dysfunction is detected early, hyperbaric oxygen might
      be beneficial if treatment is initiated within 72 hours of visual loss. Because
      of the poor prognosis associated with RION, the risk of its potential development
      should be factored into the decision to irradiate the brain.

PMID- 18068990
TI  - Delayed intracerebral abscess due to retained bike wheel valve cap.
AB  - We present a case of delayed intracerebral abscess due to retained bike wheel
      valve cap after head trauma.

PMID- 18068991
TI  - Long-term outcome of vagus nerve stimulation therapy in patients with refractory
      epilepsy.
AB  - We retrospectively assessed the long-term efficacy of vagus nerve stimulation
      (VNS) therapy in 31 patients with refractory partial and generalized seizures who
      were not candidates for resective epilepsy surgery. Following implantation of VNS
      there was significant improvement in seizure frequency at 6 months. Sixteen
      patients continued to have sustained response to VNS therapy 4 years later.
      Adverse effects of VNS therapy were transient and tolerable. The majority of the
      patients did not gain body weight and some of them had significant weight loss.
      Therefore VNS is safe and effective therapy and has a long-term sustained effect
      in refractory epilepsy.

PMID- 18068992
TI  - Resolution of dopamine dysregulation syndrome following cessation of dopamine
      agonist therapy in Parkinson's disease.
AB  - Repetitive and compulsive behaviours can occur in association with the use of
      dopaminergic medications for the treatment of Parkinson's disease (PD). This
      syndrome has been referred to as the 'dopamine dysregulation syndrome'. The
      prognosis for patients with this syndrome is unclear. We report five PD patients
      in whom the abnormal behaviours resolved completely after withdrawal of dopamine
      agonist therapy. We alert clinicians to the apparent role of dopamine agonists in
      this syndrome. In addition, we highlight the potential reversibility of the
      syndrome, its varied phenomenology and its potential pathophysiology.

PMID- 18068993
TI  - Designed modification of partial agonist of ORL1 nociceptin receptor for
      conversion into highly potent antagonist.
AB  - Nociceptin is an endogenous agonist ligand of the ORL1 (opioid receptor-like 1)
      receptor, and its antagonist is a potential target of therapeutics for analgesic
      and antineuropathy drugs. Ac-RYYRIK-NH(2) is a hexapeptide isolated from the
      peptide library as an antagonist that inhibits the nociceptin activities mediated
      through ORL1. However, the structural elements required for this antagonist
      activity are still indeterminate. In the present study, we evaluated the
      importance of the acetyl-methyl group in receptor binding and activation,
      examining the peptides acyl-RYYRIK-NH(2), where acyl (R-CO) possesses a series of
      alkyl groups, R=C(n)H(2n+1) (n=0-5). The isovaleryl derivative with the C(4)H(9)
      (=(CH(3))(2)CHCH(2)-) group was found to reveal a high receptor-binding affinity
      and a strong antagonist nature. This peptide achieved a primary goal of
      eliminating the agonist activity of Ac-RYYRIK-NH(2) and producing pure antagonist
      activity.

PMID- 18068994
TI  - New QSAR combined strategy for the design of A1 adenosine receptor agonists.
AB  - Combined discriminant and regression analysis was carried out on a series of 167
      A1 adenosine receptor agonists to identify the best linear and nonlinear models
      for the design of new compounds with a better biological profile. On the basis of
      the best linear discriminant analysis and both linear and nonlinear Multi Layer
      Perceptron neural networks regression, we have designed and synthesized 14
      carbonucleoside analogues of adenosine. Their biological activities were
      predicted and experimentally measured to demonstrate the capability of our model
      to avoid the prediction of false positives. A good agreement was found between
      the calculated and observed biological activity.

PMID- 18068995
TI  - High spatial resolution surface imaging and analysis of fungal cells using SEM
      and AFM.
AB  - We review the use of scanning electron microscopy (SEM), atomic force microscopy
      (AFM) and force spectroscopy (FS) for probing the ultrastructure, chemistry,
      physical characteristics and motion of fungal cells. When first developed, SEM
      was used to image fixed/dehydrated/gold coated specimens, but here we describe
      more recent SEM developments as they apply to fungal cells. CryoSEM offers high
      resolution for frozen fungal samples, whereas environmental SEM allows the
      analysis of robust samples (e.g. spores) under ambient conditions. Dual beam SEM,
      the most recently developed, adds manipulation capabilities along with element
      detection. AFM has similar lateral and better depth resolution compared to SEM,
      and can image live cells including growing fungal hyphae. FS can analyze cell
      wall chemistry, elasticity and dynamic cell characteristics. The integration of
      AFM with optical microscopy will allow examination of individual molecules or
      cellular structures in the context of fungal cell architecture. SEM and AFM are
      complementary techniques that are clarifying our understanding of fungal biology.

PMID- 18068996
TI  - Warm ischemia provokes inflammation and regional hypercoagulability within the
      heart during off-pump coronary artery bypass: a possible target for serine
      protease inhibition.
AB  - OBJECTIVE: Accumulating evidence suggests that a hypercoagulable state influences
      early graft failure after off-pump coronary artery bypass (OPCAB). We
      hypothesized that regional myocardial ischemia caused by obligatory periods of
      coronary occlusion during OPCAB is an important trigger for this prothrombotic
      state. METHODS: Using a series of biomarkers, 60 consecutive patients undergoing
      OPCAB were monitored for myocardial injury (myoglobin), inflammation (TNF-alpha,
      IL-8) and thrombosis (thrombin generation-F1.2, contact activation pathway-FXII
      a, platelet derived microparticles-via flow cytometry). The transcardiac
      gradients of these markers were determined by assaying both arterial and coronary
      sinus blood just after protamine administration. Intramyocardial pH was monitored
      continuously during coronary occlusion in a subset (N=30 grafts, 11 patients).
      The influence of management strategies affecting hemostasis (e.g. antiplatelet
      therapy, anti-fibrinolytics, peak activated clotting time (ACT) during
      heparinization) was analyzed. RESULTS: Ischemic injury, depicted by the
      transcardiac myoglobin gradient, significantly correlated with intramyocardial
      acidosis during coronary occlusion (R=0.96, p<0.0001) and predicted the
      transcardiac gradients of TNF-alpha (R=0.83, p<0.001) and F1.2 (R=0.72,
      p<0.0001). Transcardiac F1.2 strongly correlated with TNF-alpha (R=0.73, p=0.01)
      and IL-8 (R=0.51, p=0.02). Patients receiving aprotinin (N=20) showed
      significantly lower transcardiac gradients for myoglobin (4.1+/-7.5% vs 72.9+/
      108.8% change, p=0.002), F1.2 (31+/-37% vs 89+/-149%, p=0.03), FXII-a (2.6+/-4.1%
      vs 19.2+/-34%, p=0.04) and microparticles (7+/-3.9% vs 12.9+/-8%, p=0.01).
      CONCLUSIONS: Strong correlations between myocardial ischemia and the transcardiac
      gradients of markers for inflammation and thrombosis suggest that even brief
      episodes of coronary occlusion in the beating heart may have pathophysiologic
      consequences. Aprotinin, but not other factors that influence the coagulation
      system, appears to mitigate this process during OPCAB.

PMID- 18068997
TI  - Depression and cancer: an unexplored and unresolved emergent issue in elderly
      patients.
AB  - Despite the high prevalence of depressive disorders in cancer patients and
      elderly people, the topic of depression in elderly cancer patients still remains
      unexplored. This emerges from a systematic review of the literature conducted to
      investigate issues of depression, diagnosis, pathogenesis, treatment and their
      complex neuroimmunobiological interactions. Indeed, it becomes apparent that
      depression in elderly patients with cancer may have a peculiar phenomenology. In
      addition, the moderate rate of major depressive disorder and the high rate of
      minor depressive disorder are accompanied by subthreshold forms of depression
      that are at risk to be underrecognized and untreated. Immune dysfunction may
      represent a common pathogenic ground of depression, cancer and aging. This may
      have important implications for treatment. In the near future, we need to develop
      validated mood disorder diagnoses and verify antidepressant treatment efficacy
      for elderly cancer patients with depression in order to improve their clinical
      outcome and quality of life.

PMID- 18068998
TI  - Positive and negative signaling components involved in TNFalpha-induced NF-kappaB
      activation.
AB  - Tumor Necrosis Factor alpha (TNFalpha) is a pro-inflammatory cytokine that plays
      important roles in different biological processes, including the induction of
      other cytokines. One of the most important downstream signaling targets activated
      by TNFalpha is the NF-kappaB transcription factor, which has been identified to
      be involved in inflammatory, anti-apoptotic, and immune responses. Stimulation of
      cells with TNFalpha triggers activation of NF-kappaB through various signaling
      molecules, including TRAF2, RIP, MAP3K, and the IKK complex. Recently, numerous
      studies have been performed to explore the detailed mechanism by which NF-kappaB
      is activated upon TNFalpha stimulation. Current understanding of this pathway has
      been focused on the identification of signaling components, the role of post
      translational modification and the sub-cellular translocation of those
      components. Additionally, more negative regulators in the TNF-IKK pathway are
      emerging.

PMID- 18068999
TI  - Relaxin induces mast cell inhibition and reduces ventricular arrhythmias in a
      swine model of acute myocardial infarction.
AB  - Resident cardiac mast cells, located mainly around coronary vessels and in the
      right atrium close to the sinoatrial node, are the main repository of cardiac
      histamine. Inflammatory activation of cardiac mast cells, as occurs upon acute
      myocardial infarction, causes the release of histamine and prostanoids. These
      substances lead to severe tachyarrhythmias, cardiodepressive effects and coronary
      spasm, thus contributing to myocardial damage and early, lethal outcome. Relaxin,
      known to inhibit mast cell activation, has been recently validated as a
      cardiotropic hormone, being produced by the heart and acting on specific heart
      receptors. In this study, we report on a swine model of heart
      ischemia/reperfusion, currently used to test cardiotropic drugs, in which human
      recombinant relaxin (2.5 and 5 microg/kg b.w.), given at reperfusion upon a 30
      min ischemia, markedly reduced cardiac injury as compared with the vehicle
      treated animals. Evidence is provided that relaxin, at both the assayed doses,
      causes a clear-cut, significant reduction of plasma histamine, increase in
      cardiac histamine content and decrease in cardiac mast cell degranulation. This
      is accompanied by a reduction of oxidative cardiac tissue injury (assessed as
      tissue malondialdehyde) and of the occurrence of severe ventricular arrhythmias.
      In conclusion, this study provides further insight into the cardioprotective
      effects of relaxin, which also involve mast cell inhibition, and confirms the
      relevance of histamine in the pathophysiology of ischemia-reperfusion-induced
      cardiac injury and dysfunction. It also offers additional evidence for the
      potential therapeutic effects of relaxin in animal models of disease involving
      mast cell activation.

PMID- 18069001
TI  - Evaluating differential item functioning of the PRIME-MD mood module among
      impoverished black and white women in primary care.
AB  - BACKGROUND: Appropriate treatment of depression requires accurate screening and
      diagnosis. It is important to evaluate depression screening instruments for
      differential item functioning (DIF) across diverse populations. The PRIME-MD is
      commonly used in primary care settings to screen for the most common psychiatric
      disorders, including depression. The purpose of this study was to determine
      whether items in the mood module of the PRIME-MD perform similarly in 2 high-risk
      populations: impoverished black and white women. METHODS: Data were collected
      during screening for a randomized controlled trial of treatment for depression in
      women receiving county health and welfare services. Analyses are based on a
      sample of 3,506 black (n = 3,191) and white (n = 315) women who completed the
      PRIME-MD mood module. Responses were compared using an item response theory
      approach to DIF assessment. Mean scores, missing data, and internal consistency
      reliability were also compared. RESULTS: None of the 9 items exhibited
      significant DIF. Missing data rates and internal consistency reliability did not
      differ for the 2 groups. Mean comparisons indicated that white women endorsed
      higher levels of depression compared with black women on 6 of the 9 items (p <
      .05). CONCLUSIONS: These results suggest that all items of the mood module of the
      PRIME-MD performed similarly for white and black women. Differences in endorsed
      depressive symptomatology on the mood module may be attributed to actual
      differences in DSM-IV depression symptoms between white and black women.

PMID- 18069000
TI  - Expedited approaches to whole cell electron tomography and organelle mark-up in
      situ in high-pressure frozen pancreatic islets.
AB  - We have developed a simplified, efficient approach for the 3D reconstruction and
      analysis of mammalian cells in toto by electron microscope tomography (ET), to
      provide quantitative information regarding 'global' cellular organization at
      approximately 15-20 nm resolution. Two insulin-secreting beta cells-deemed
      'functionally equivalent' by virtue of their location at the periphery of the
      same pancreatic islet-were reconstructed in their entirety in 3D after fast
      freezing/freeze-substitution/plastic embedment in situ within a glucose
      stimulated islet of Langerhans isolated intact from mouse pancreata. These
      cellular reconstructions have afforded several unique insights into fundamental
      structure-function relationships among key organelles involved in the
      biosynthesis and release of the crucial metabolic hormone, insulin, that could
      not be provided by other methods. The Golgi ribbon, mitochondria and insulin
      secretory granules in each cell were segmented for comparative analysis. We
      propose that relative differences between the two cells in terms of the number,
      dimensions and spatial distribution (and for mitochondria, also the extent of
      branching) of these organelles per cubic micron of cellular volume reflects
      differences in the two cells' individual capacity (and/or readiness) to respond
      to secretagogue stimulation, reflected by an apparent inverse relationship
      between the number/size of insulin secretory granules versus the number/size of
      mitochondria and the Golgi ribbon. We discuss the advantages of this approach for
      quantitative cellular ET of mammalian cells, briefly discuss its application
      relevant to other complementary techniques, and summarize future strategies for
      overcoming some of its current limitations.

PMID- 18069002
TI  - Ethnic differences in the correlates of mental distress among homeless women.
AB  - BACKGROUND: Homeless women experience high rates of mental distress. We sought to
      determine whether ethnic differences exist in the relationship between the
      predisposing and enabling domains of the Gelberg-Andersen Behavioral Model for
      Vulnerable Populations and mental distress. METHODS: We selected 821 homeless
      women in the Los Angeles area using a representative probability sampling design
      and invited them to participate in face-to-face interviews. The sample was 67%
      African American, 17% Hispanic, and 16% White. RESULTS: We identified a number of
      ethnic differences in the correlates of mental distress. Being partnered or
      married was associated with greater distress among African American and White
      women, and experiencing competing needs was predictive of distress for African
      Americans and Hispanics. CONCLUSION: A variety of factors contribute to mental
      distress among different ethnic groups of homeless women; these differences
      should be considered in the development of culturally appropriate services
      designed to address mental health problems among homeless populations.

PMID- 18069004
TI  - Gender differences in brain activity evoked by muscle and cutaneous pain: a
      retrospective study of single-trial fMRI data.
AB  - Gender greatly influences pain processing. Not only do females display greater
      pain sensitivity, many chronic pain conditions affect females more than males.
      Although gender-based differences in pain sensitivity may be related to cultural
      and social factors, animal studies also reveal gender differences in pain
      sensitivity, suggesting that physiological factors may contribute to differences
      in the processing of pain in males and females. It has been recently reported
      that noxious cutaneous heat stimuli evoke gender-based differences in activity in
      some brain regions. Given that most chronic pain conditions, including those with
      gender bias are of "deep" origin (e.g. arising in muscle, joints or viscera), we
      investigated whether gender differences also exist in the central processing of
      muscle pain. In 24 healthy adults we used functional magnetic resonance imaging
      (fMRI) to measure signal intensity changes during muscle and cutaneous pain
      induced by intramuscular and subcutaneous injections of hypertonic saline,
      respectively. In addition to activating the "pain neuromatrix", i.e. cingulate,
      insular, somatosensory and cerebellar cortices, both muscle pain and cutaneous
      pain evoked gender-based differences in the mid-cingulate cortex, dorsolateral
      prefrontal cortex, hippocampus and cerebellar cortex. These differences may
      reflect differences in emotional processing of noxious information in men and
      women and may underlie the gender bias that exists in many chronic pain
      conditions.

PMID- 18069003
TI  - A sociobehavioral model of acupuncture use, patterns, and satisfaction among
      women in the United States, 2002.
AB  - OBJECTIVES: To examine the correlates of recent acupuncture use among American
      women, applying a sociobehavioral model of utilization of conventional health
      care. Patterns of use, satisfaction, and reasons for acupuncture use are also
      examined. METHODS: The 2002 National Health Interview Survey (NHIS) is used,
      which included the Alternative Health/Complementary Alternative Medicine
      Supplement. All analyses and estimates used the NHIS individual-level sampling
      weights; variance estimates were adjusted to account for complex sample design.
      Bivariate statistics and logistic regression were used. We included data from
      17,112 women. RESULTS: Prevalence of recent acupuncture use was low (1.1%), but
      translates to >1.2 million American women. Multivariate results showed the
      effects of race and ethnicity on acupuncture use were contingent on educational
      level. Women living in the West were more likely to use acupuncture, as were
      women with fair health status, former smokers, current moderate/heavy alcohol
      users, and women with a higher body mass index. Women tended to use acupuncture
      for conditions not commonly well treated by conventional medicine (e.g., chronic
      pain) and the majority reported using acupuncture in conjunction with
      conventional medicine. CONCLUSIONS: Predisposing and enabling factors, as well as
      medical need and personal health practices, are associated with women's recent
      use of acupuncture services, including several that are also associated with
      conventional health care services.

PMID- 18069005
TI  - Superior dislocation of the sternoclavicular joint.

PMID- 18069006
TI  - Osteoarthritis of the elbow: results of arthroscopic osteophyte resection and
      capsulectomy.
AB  - Primary osteoarthritis of the elbow involves formation of bony spurs, loose
      bodies, and capsular contracture. This article presents the results of an
      arthroscopic technique for treatment of elbow arthritis in a series of patients.
      A retrospective chart review identified 41 patients with primary osteoarthritis
      in 42 elbows who underwent arthroscopic osteophyte resection and capsulectomy and
      who had more than 2 years of follow-up. Preoperative motion, pain, and Mayo Elbow
      Performance Index scores were compared with those at the latest follow-up. At an
      average follow-up of 176.3 weeks, significant improvements occurred in mean
      flexion, from 117.3 degrees preoperatively to 131.6 degrees (P < .0001);
      extension, from 21.4 degrees to 8.4 degrees (P < .0001); supination, from 70.7
      degrees to 78.6 degrees (P = .0056); and Mayo Elbow Performance Index scores (P <
      .0001), with 81% good to excellent results. Pain decreased significantly (P <
      .0001). Complications were rare (n = 2) and included heterotopic ossification and
      ulnar dysesthesias. This procedure addresses the pathologic processes associated
      with arthritis of the elbow and was safe and effective in this series.

PMID- 18069007
TI  - Unstable elbow dislocations.
AB  - Seventeen patients with a posterior dislocation of the elbow and either no
      fracture or a minimal capsuloligamentous avulsion fracture were treated
      operatively for persistent redislocation after manipulative reduction. Fifteen
      had open reduction and ligament repair (3 with ancillary hinged external
      fixation), and 2 infirm patients had closed reduction and cross pinning of the
      elbow joint. Among the 12 patients treated with ligament repair alone, 1
      redislocated (treated with a second surgery for hinged external fixation) and 4
      had residual subluxation (treated with temporary casting of protected active
      exercises) after ligament repair alone (42% residual instability). A concentric,
      stable elbow was eventually achieved in all 17 patients. The average flexion arc
      was 113 degrees . The average Broberg and Morrey score was 88, with 3 excellent,
      10 good, and 2 fair results. A small percentage of elbow dislocations require
      operative treatment. Ligament repair alone may not be sufficient, and protection
      with a hinged external fixator is recommended.

PMID- 18069008
TI  - Arthroscopic rotator cuff repair in patients younger than fifty years of age.
AB  - Thirty-seven patients (41 shoulders) younger than 50 years of age (mean age, 43.7
      years) underwent all-arthroscopic repairs of rotator cuff tears between 1994 and
      2002. With a minimum 3-year follow-up (average 69 months, range 37-161 months),
      postoperative function was assessed by means of a UCLA scoring system, range of
      motion measurements, strength exam, and VAS pain score. Tears were categorized
      into 4 groups by type and size: partial undersurface tears, complete tears that
      were small (<1 cm), medium (1-3 cm), or large/massive (4-5 cm). All but 1 patient
      (97%) was subjectively satisfied and felt to be improved postoperatively. Average
      postoperative UCLA score improved significantly, and 95% of the shoulders
      achieved good or excellent postoperative results. Postoperative pain scores and
      strength evaluation also improved significantly. There was no significant loss of
      motion postoperatively and outcomes were independent of tear size and type. To
      date, there have been no revisions. These treatment results suggest that
      arthroscopic management in patients younger than 50 can achieve predictably good
      to excellent results regardless of tear size.

PMID- 18069009
TI  - Shoulder and elbow arthroplasty: one-stage or two-stage.
AB  - Multiple joint replacement in 1 operative session is frequently performed in the
      lower extremity but less often in the upper extremity. The purpose of the present
      study is to determine whether a 1-stage arthroplasty of the ipsilateral shoulder
      and elbow affects the clinical outcome. Replacement of the ipsilateral shoulder
      and elbow was performed in 34 rheumatoid patients (42 upper extremities). In 11
      patients (13 upper limbs), the shoulder and elbow arthroplasty was a 1-stage
      procedure. The average follow-up of the whole group was 4.5 years (range, 2-12
      years). The patients were in a prospective study and evaluated clinically and
      radiographically. With a 1-stage procedure, the hospitalization time was shorter.
      The overall Hospital for Special Surgery shoulder score and its items (pain,
      function, and strength) were similar at follow-up in the 2 groups, and only the
      motion score showed more improvement in the 1-stage group. The clinical outcome
      of elbow arthroplasty was similar in both groups, regardless of the sequence of
      surgery. From this study, it may be concluded that a 1-stage procedure for
      shoulder and elbow arthroplasty will reduce the hospitalization time and does not
      adversely affect the clinical outcome.

PMID- 18069010
TI  - A biomechanical comparison of repair techniques in posterior type II superior
      labral anterior and posterior (SLAP) lesions.
AB  - The purpose of this study was to compare the 3 different fixation methods of
      posterior type superior labral anterior posterior (SLAP) II lesion. Fifteen
      cadavers were randomly divided into 3 groups to compare the initial strength of 3
      different fixation methods in posterior type II SLAP lesions. Group I used 1
      anchor for 1-point fixation with a conventional simple suture; group II used 1
      anchor passing both limbs through the posterior-superior labrum in a mattress
      fashion; and group III used 2 anchors for 2-point fixation with conventional
      simple sutures. Repair failure (2 mm permanent displacement of repaired site) and
      ultimate failure were measured. The mean load to (clinical) failure was 156 +/-
      22 N in group I, 117 +/- 33 N in group II, and 161 +/- 44 N in group III. The
      mean load to ultimate failure was 198 +/- 6 N in group I, 189 +/- 23 N in group
      II, and 179 +/- 22 N in group III. The specimen stiffness was equivalent among
      groups. In mode of failure, clinical failure (more than 2 mm separations) first
      occurred between the markers on the biceps tendon just above (A) and below (B)
      compared to other markers, and ultimate failure occurred at the labral-implant
      interface. A single simple suture anchor repair in posterior type II SLAP seems
      sufficient to withstand the initial load without clinical failure. A mattress
      suture, although it anchors the biceps root, seems to be inferior than simple
      suture technique.

PMID- 18069011
TI  - Extracorporeal shock wave therapy for calcifying tendinitis of the shoulder.
AB  - We prospectively studied extracorporeal shock wave therapy (ESWT) for calcific
      tendinitis of the shoulder in 46 consecutive patients. All patients were randomly
      divided into 2 groups: treatment and control. The 33 patients in the treatment
      group received 2 courses of ESWT at the energy density of 0.55 mJ/mm(2) (1000
      impulses). The control group underwent sham treatment with a dummy electrode (13
      patients). Evaluation included the Constant score, pain scale, and radiographs.
      The ESWT results were good to excellent in 87.9% of shoulders (29/33) and fair in
      12.1% (4/33), and the control results were fair in 69.2% (9/13) and poor in 30.1%
      (4/13). Among ESWT patients, calcium deposits were completely eliminated in 7
      cases (21.2%), partially eliminated in 11 (36.3%), and unchanged in 15 (45.4%).
      In contrast, elimination was partial in 2 control patients (15.3%) and unchanged
      in 11 (84.7%). There was no significant difference between Gartner type I and
      type II groups in the Constant score (P > .05). ESWT shows promise for pain
      relief and functional restoration of calcific tendinitis with negligible
      complications.

PMID- 18069012
TI  - Treatment of fractures adjacent to humeral prostheses.
AB  - Fifteen patients with fractures adjacent to a humeral prosthesis were treated
      between 1986 and 2002. There were 10 females and 5 males. The average age was 58
      years. The fractures were classified as to location relative to the prosthesis.
      Type I fractures (N = 3) occurred proximal to the tip of the prosthesis. Type II
      fractures (N = 7) occurred in which the fracture line extended from the proximal
      portion of the humeral shaft to beyond the distal tip of the prosthesis. Type III
      (N = 5) fractures occurred entirely distal to the tip of the prosthesis. Two type
      I and 3 type II fractures were managed with a fracture orthosis. The remainder of
      the fractures were treated surgically with a combination of cerclage wires and
      long stem prosthesis. All fractures progressed to union at an average of 11
      weeks. Average forward elevation for the group was 124 degrees . No patient
      required a shoulder spica or bone grafting to obtain union. Treatment resulted in
      fracture union, prosthesis stability, and a paucity of complications.

PMID- 18069013
TI  - Contrast-enhanced ultrasound characterization of the vascularity of the rotator
      cuff tendon: age- and activity-related changes in the intact asymptomatic rotator
      cuff.
AB  - The natural history of the blood supply to the rotator cuff and its role in the
      etiology of rotator cuff disease has not been definitively established. To date,
      there has not been an in-vivo dynamic assessment of the baseline vascularity of
      the asymptomatic rotator cuff. This study was designed to test the hypothesis
      that regional variations in supraspinatus tendon vascularity exist with an age
      dependent decrease in asymptomatic individuals with intact rotator cuffs. Lipid
      microsphere, contrast-enhanced ultrasound shoulder examinations were done in 31
      patients with a mean age of 41.5 years (range, 22-65 years). Images were obtained
      at baseline, after contrast administration at rest, and after contrast
      administration following exercise to visualize the intratendinous blood flow to
      the supraspinatus tendon. Qualitative and quantitative analysis was performed by
      determining 4 regions of interest (bursal medial, articular medial, bursal
      lateral, and articular lateral) with quantification and analysis software (QLAB
      Philips, Andover, MA) to examine each region of interest and normalize data for
      interpretation of the mean intensity per pixel. A statistically significant
      decrease in blood flow to the supraspinatus tendon with age was observed in a
      comparative analysis of patients aged younger than 40 and older than 40, (P < .05
      for all 4 zones after exercise and for the bursal medial, articular medial, and
      bursal lateral zones after exercise; P = .07 for the articular lateral zone after
      exercise). A statistically significant increase in blood flow with exercise was
      observed in an analysis of all patients (P < .001). The age-related decrease in
      the vascular supply of the tendon observed in this study is consistent with
      published reports demonstrating an increasing prevalence of rotator cuff
      pathology with age and may predispose to the development of rotator cuff
      tendinopathy and, ultimately, attritional tears.

PMID- 18069014
TI  - The strength of the rotator cuff before and after subacromial injection of
      lidocaine.
AB  - The purpose of this study was to evaluate the strength of the shoulder before and
      after the impingement test. This study included 153 cases of impingement
      syndrome, 20 cases of partial-thickness rotator cuff tear, and 60 cases of full
      thickness rotator cuff tear. We divided each of the groups into 2 subgroups
      according to the mean percentage decrease in pain to evaluate the correlation
      between pain and muscle weakness. We also divided the impingement syndrome group
      into 2 groups based on stiffness. After the test, the subgroup with stiffness had
      a greater reduction in pain compared with the subgroup without stiffness. The
      results show no statistically significant difference in the strength of the
      shoulder, except for increased external rotation strength in patients with full
      thickness rotator cuff tears and increased supraspinatus strength in patients
      with impingement syndrome with stiffness. In cases in which the continuity of the
      rotator cuff is maintained, pain is not an important factor in the cause of
      shoulder weakness. Preoperative muscle testing can be done despite pain, but if a
      full-thickness rotator cuff tear is confirmed, re-examination of external rotator
      strength is necessary. In patients with impingement syndrome, particularly with
      shoulder stiffness, supraspinatus strength can be decreased.

PMID- 18069015
TI  - The block-bridge system: a new concept and surgical technique to reconstruct
      articular surfaces and tuberosities in complex proximal humeral fractures.
AB  - Surgical treatment of complex displaced fractures of proximal humerus has changed
      in the last few years. Osteosynthesis has a high rate of nonunion, malunion, and
      avascular necrosis, and the results of hemiarthroplasty are not always
      functionally satisfactory. We report the results of a new technique for the
      reconstruction of the proximal humerus around a triangular-shaped bone block
      positioned inside the head and the metaphysis. The fragments are stabilized with
      minimal osteosynthesis by Kirschner wires, screws, or sutures. From 2001 to 2005,
      we treated 33 patients (20 men, 13 women) aged 34 to 74 years. The functional
      results were evaluated by the Constant score, with a mean follow-up of 24 months
      (range,12-36 months) The mean Constant score was 68 (range, 47-90). The results
      were excellent or good in 23 patients. The mean active anterior elevation was 160
      degrees , all were pain free, and they returned to their preoperative activities,
      including sports. One patient had a symptomatic avascular necrosis that was
      treated with a hemiarthroplasty. The results show that this new technique has
      good clinical results with a low percentage of complications.

PMID- 18069016
TI  - A pilot randomized, controlled trial of treatment for painful arc of the
      shoulder.
AB  - There is a lack of evidence about the efficacy of routinely used interventions in
      shoulder pain, such as corticosteroid injection and physiotherapy. This pilot
      study was set up to assess the feasibility of a larger, randomized controlled
      trial. Patients with the clinical presentation of a painful arc of less than 6
      months' duration were recruited through their general practitioners. A total of
      112 patients were randomized to 4 groups: control, physiotherapy, a course of
      subacromial steroid injections, or both physiotherapy and steroid injections. The
      primary outcome measure was the Oxford Shoulder Score (OSS). Follow-up was 18
      weeks and by postal questionnaire at 1 year. No significant differences were
      found within groups between the OSS scores or the Physical Health total of the
      Medical Outcomes Study Short Form 36 (SF-36) Health Survey at the beginning and
      end of the trial or at 1 year. By analysis of covariance, no significant
      differences were found between treatment groups. Larger studies are needed. A
      power calculation from our data suggests recruitment of more than 800 patients
      would be required to achieve a 90% chance of a clinically significant difference
      being detected between these groups.

PMID- 18069017
TI  - Latissimus dorsi tendon transfer for massive irreparable cuff tears: an anatomic
      study.
AB  - The purpose of this study was to describe landmarks for latissimus dorsi tendon
      transfer in massive irreparable tears of the rotator cuff. Nine pairs of embalmed
      cadaveric shoulders were dissected. Crucial structures were identified, and their
      relationship with various bony and soft-tissue reference points was documented.
      Identification of the dense fibrous band, at the confluence of the teres major
      and latissimus dorsi musculotendinous unit, facilitates localization of the
      radial nerve, which crosses deep to this landmark. The axillary nerve can be seen
      to exit the quadrangular space 27 mm medial to the latissimus dorsi insertion
      into the proximal humerus, whereas the thoracodorsal neurovascular pedicle
      inserts into the latissimus dorsi 110 mm from the humeral tendon's humeral
      attachment. Harvest of the latissimus dorsi tendon can be safely accomplished by
      identifying the dense fibrous band and releasing the tendon within 2 cm of its
      humeral attachment.

PMID- 18069018
TI  - Elbow function after repair of the distal biceps brachii tendon with a two
      incision approach.
AB  - A modified Boyd-Anderson 2-incision approach is commonly used to repair the
      distal biceps tendon after avulsion from the radial tuberosity. Using suture
      anchors for fixation instead of a bone trough simplifies the procedure. This
      retrospective study enrolled 32 patients who underwent surgical repair of the
      distal biceps tendon with a 2-incision approach and 2 suture anchors. The mean
      postoperative follow-up was 42 months. Elbow strength, endurance, and range of
      motion for flexion, pronation, and supination were measured for each arm. For
      each strength and endurance measurement, the mean for the involved arm was at
      least 95% of that for the uninvolved arms. The largest flexion, pronation, and
      supination deficits for an injured arm, as compared with the uninjured arm, were
      9 degrees, 15 degrees, and 16 degrees, respectively. A 2-incision approach for
      distal biceps tendon repair with suture anchor fixation can restore elbow
      function and satisfy patients.

PMID- 18069019
TI  - Voltage-dependent potassium channels are involved in staurosporine-induced
      apoptosis of rat mesenchymal stem cells.
AB  - The strategy of mesenchymal stem cells (MSCs) transplantation is limited by the
      inability to deliver a large number of grafted cells that resist peri
      transplantation apoptosis in ischemic tissues, and this led us to investigate
      methods of improving the viability of these cells. We demonstrate the presence of
      voltage-gated potassium channels in rat MSCs that can be activated by
      staurosporine (ST). MSCs exposed to ST underwent apoptotic cell changes.
      Tetraethylammonium (TEA), a classic blocker of K+ channels, blocked the ST
      induced augmentation of K+ currents, and reduced ST-induced apoptosis.
      Furthermore, we found that TEA prevented the ST-induced increase in expression of
      the pro-apoptotic protein Bax and decrease of the anti-apoptotic protein Bcl-2.
      Taken together, our findings suggest that voltage-gated potassium is involved in
      ST-induced apoptosis of rat MSCs. TEA blocks the ST-induced augmentation of K+
      currents, alters the expression of Bcl-2 family proteins induced by ST, and
      attenuates the apoptosis of rat MSCs.

PMID- 18069020
TI  - Rigidity in social and emotional memory in the R6/2 mouse model of Huntington's
      disease.
AB  - Four experiments were conducted to examine social and emotional memory in the
      R6/2 transgenic mouse model of Huntington's disease. First, R6/2 mice were tested
      in a social transmission of food preference task where they had to acquire a
      preference for a flavoured food (acquisition) and subsequently to learn a
      preference for a different flavour (shifted reinforcement). R6/2 mice performed
      well in the acquisition trial. However, they were impaired in the shifted
      reinforcement trial and perseverated on the first preference learned. Second,
      mice were trained in an inhibitory avoidance paradigm, with either one or two
      footshocks delivered during the training. WT mice given one footshock showed
      retention levels lower than those of mice trained with two footshocks. By
      contrast, there was no difference in retention levels of R6/2 mice given either
      one or two footshocks. Third, mice were tested in an active avoidance task that
      paired a mild footshock with a warning light. R6/2 mice had a strong age
      dependent deficit in this task. Finally, mice were tested in a conditioned taste
      aversion task that paired a saccharine solution with a nausea-inducing agent
      (LiCl). R6/2 mice displayed normal aversion, however this was not extinguished
      following repeated exposure to saccharine solution alone. Our data show that
      while R6/2 mice have functional hippocampus-based memory, they have deficits in
      striatum-based memory skills. Further, social and emotional memories appear to be
      encoded in a rigid way that is not influenced by subsequent learning or by
      arousal levels.

PMID- 18069021
TI  - Thoracoabdominal aortic aneurysm repair in patients with marfan syndrome.
AB  - OBJECTIVE: We assessed the surgical outcome of descending thoracic aortic
      aneurysm repair (DTAA) and thoracoabdominal aortic aneurym (TAAA) repair in
      patients with Marfan syndrome. METHODS: During a six year period, 206 patients
      underwent DTAA and TAAA repair. In 22 patients, Marfan syndrome was confirmed.
      The median age was 40 years with a range between 18 and 57 years. The extend of
      the aneurysms included 6 DTAA (1 with total arch, 2 with distal hemi-arch), 11
      type II TAAA (2 with total arch, 3 with distal hemi-arch), 4 type III and one
      type IV TAAA. All patients suffered from previous type A (n=6) or type B (n=16)
      aortic dissection and 15 already underwent aortic procedures like Bentall (n=7)
      and ascending aortic replacement (n=8). All patients were operated on according
      to the standard protocol with cerebrospinal fluid drainage, distal aortic and
      selective organ perfusion and monitoring motor evoked potentials. In patients
      undergoing simultaneous arch replacement (via left thoracotomy), transcranial
      Doppler and EEG assessed cerebral physiology during antegrade brain perfusion. In
      four patients circulatory arrest under moderate hypothermia was required.
      RESULTS: In-hospital mortality did not occur. Major postoperative complications
      like paraplegia, renal failure, stroke and myocardial infarction were not
      encountered. Mean pre-operative creatinine level was 125mmol/L, which peaked to a
      mean maximal level of 130 and returned to 92mmol/L at discharge. Median
      intubation time was 1.5 days (range 0.33-30 days). Other complications included
      bleeding requiring surgical intervention (n=1), arrhythmia (n=2), pneumonia (n=2)
      and respiratory distress syndrome (n=1). At a median follow-up of 38 months all
      patients were alive. Using CT surveillance, new or false aneurysms were not
      detected, except in one patient who developed a visceral patch aneurysm six years
      after open type II repair. CONCLUSION: Surgical repair of descending and
      thoracoabdominal aortic aneurysms provides excellent short- and mid-term results
      in patients with Marfan syndrome. In this series, a surgical protocol with
      cerebrospinal fluid drainage, distal aortic and selective organ perfusion and
      monitoring motor evoked potentials resulted in low morbidity and absent
      mortality. These outcomes of open surgery should be considered when discussing
      endovascular aneurysm repair in Marfan patients.

PMID- 18069022
TI  - Level of ex vivo interleukin 6 expression in human peripheral fat compared with
      other tissues.
AB  - OBJECTIVES: Adipose tissue is able to secrete a variety of active mediators into
      the circulation. One of these is Interleukin 6 (IL6). IL6 may play a causal role
      in the development of atherosclerosis. It has therefore been suggested that IL6
      may form part of the link between obesity and vascular disease. The aim of this
      study was to quantify the relative IL6 expression in adipose tissue compared to
      other tissues. METHODS: Tissue (vein, fat, muscle, blood) was collected from 32
      patients undergoing varicose vein surgery. RNA was extracted and mRNA measured
      using RT-PCR relative quantification. The mean relative IL6 mRNA levels were
      compared between tissues using the Mann Whitney U test and the independent t
      test. Tissue levels were compared for individuals using the Wilcoxon signed rank
      test. RESULTS: Mean relative IL6 mRNA levels (mean+/-SEM) were significantly
      greater in adipose tissue 44.8+/-16.1 than in other tissues (leukocytes 1.1+/
      0.3, vein 2.0+/-0.8, muscle 0.06+/-0.03: p<0.001). mRNA expression levels were
      also significantly higher in fat than in all other tissue types in individuals
      (p<0.001). CONCLUSIONS: IL6 mRNA expression is significantly higher in adipose
      than in many other tissues known to express IL6.

PMID- 18069023
TI  - Outcome after endografting in small and large abdominal aortic aneurysms: a
      metanalysis.
AB  - AIM: To compare the results of endovascular repair (EVAR) in large and small
      (diameter < 5.5cm) abdominal aortic aneurysms (AAA). METHODS: A systematic review
      was performed to identify studies comparing the outcomes after EVAR of large and
      small aneurysms. Outcomes considered were: risk of death (perioperative, all
      cause, aneurysm-related), ruptures, and complications (conversion,
      reintervention). Weighted pooled estimates of outcomes in patients with small
      versus large aneurysms were calculated. The inverse variance method was used
      (random-effect model). Subgroup analyses by a follow-up longer or shorter than 24
      months were performed. RESULTS: Five studies, with published and unpublished
      data, totallying 7,735 patients, were included. Overall, the weighted pooled
      estimates were: OR 0.68; 95% CI 0.51-0.90 for operative mortality, OR 0.77; 95%
      CI 0.69 to 0.86 for all cause mortality, OR 0.58; 95% CI 0.40 to 0.87 for
      aneurysm-related mortality and OR 0.61; 95% CI 0.47 to 0.79 for rupture in favour
      of small AAA group. Pooled estimates were not influenced by follow-up length.
      Conversion and reintervention rates were not significantly lower for small AAA.
      CONCLUSIONS: EVAR in small versus large AAA might be associated with lower
      operative mortality, aneurysm-related mortality and aneurysm rupture. Better
      evidence is needed to support these suggestions.

PMID- 18069024
TI  - Microtubule dynamics and the role of molecular motors in Neurospora crassa.
AB  - Live-cell imaging methods were used to study microtubule dynamics in the apical
      regions of leading hyphae and germ tubes of Neurospora crassa expressing beta
      tubulin-GFP. Microtubule polymerization rates in hyphae of N. crassa were much
      faster than those previously reported in any other eukaryotic organism. In order
      to address the roles of motor proteins in microtubule dynamic instability in N.
      crassa, the microtubule-motor mutant strains, Deltankin and ro-1, were examined.
      Polymerization and depolymerization rates in leading hyphae of these strains were
      reduced by one half relative to the wild type. Furthermore, microtubules in germ
      tubes of wild type and microtubule-motor mutants exhibited similar dynamic
      characteristics as those in hyphae of mutant strains. Small microtubule fragments
      exhibiting anterograde and retrograde motility were present in leading hyphae of
      all strains and germ tubes of wild-type strains. Our data suggest that
      microtubule motors play important roles in regulating microtubule dynamic
      instability in leading hyphae but not in germ tubes.

PMID- 18069025
TI  - Short term analgesic effect of extracorporeal shock wave therapy in horses with
      proximal palmar metacarpal/plantar metatarsal pain.
AB  - Extracorporeal shock wave therapy (ESWT) is an accepted form of treatment for
      chronic cases of proximal suspensory desmitis (PSD). Subjective evaluation of
      horses shortly after being treated with ESWT has led clinicians to comment on an
      immediate reduction in lameness. This study aimed to evaluate the analgesic
      effect of ESWT on 16 horses with PSD or PSD-like pain in a fore- or hindlimb. To
      objectively assess lameness, gait analysis was performed on an instrumented
      treadmill before and 6, 24, 48 and 72h after ESWT of the origin of the suspensory
      ligament and the results compared to the effects of local anaesthesia. Stride
      frequency, stance duration, vertical impulse and peak vertical force were
      determined. Thermographic imaging and evaluation of skin sensitivity of the
      treated area were carried out before and after ESWT in the same interval as gait
      analysis. The results showed that there were no significant improvements in the
      investigated parameters at any time after ESWT; however, in horses with affected
      forelimbs the contralateral weightbearing asymmetry decreased significantly 72h
      after ESWT. Neither skin sensitivity nor thermographic imaging revealed changes
      that could be attributed to ESWT.

PMID- 18069026
TI  - Aicardi-Goutieres syndrome presenting atypically as a sub-acute
      leukoencephalopathy.
AB  - Aicardi-Goutieres syndrome is an autosomal recessive encephalopathy characterised
      by acquired microcephaly, basal ganglia calcifications, leukodystrophy, cerebral
      atrophy, chronic cerebrospinal lymphocytosis, and raised titres of interferon
      alpha in the cerebrospinal fluid. The disease onset is generally within the first
      months of life. We here report a case of Aicardi-Goutieres syndrome presenting
      atypically as a sub-acute leukoencephalopathy following satisfactory psychomotor
      development up to the age of 16 months. This case highlights the importance of
      considering Aicardi-Goutieres syndrome in the differential diagnosis of an
      unexplained leukoencephalopathy and the possibility of later onset of the
      disease.

PMID- 18069027
TI  - Effects of simultaneous dual-site TENS stimulation on experimental pain.
AB  - Transcutaneous electrical nerve stimulation (TENS) is commonly used for pain
      relief. However, little robust research exists regarding the combination of
      parameters required to provide effective doses. This study investigated the
      hypoalgesic effects of different parameter combinations, applied simultaneously
      at two sites (segmental and extrasegmental), on pressure pain threshold (PPT) in
      pain-free humans. Two-hundred and eight volunteers (median age 22 years, range 20
      26) were randomized to eight groups: six active TENS groups, placebo and control.
      Parameter combinations were such that frequency always differed at each site (110
      Hz or 4 Hz), but intensity could be either the same or different levels: high (to
      tolerance without pain) or low (strong but comfortable). TENS was administered to
      the forearm over the radial nerve and the ipsilateral leg below the fibular head
      for 30 min with monitoring for 30 further minutes. PPT measurements were taken
      bilaterally from the mid-point of first dorsal interosseous muscle, by an
      independent blinded rater, at baseline and at six subsequent 10-min intervals.
      Log-transformed data were analysed using repeated-measures analysis of covariance
      (baseline values and gender as covariates). Those groups using high-intensity
      stimulation at the segmental stimulation sites showed significantly greater
      hypoalgesia than placebo (p < 0.025 in each case). The largest hypoalgesic effect
      was for simultaneous high-intensity stimulation at segmental and extrasegmental
      sites, using different frequencies. These results reaffirm that high-intensity
      stimulation (regardless of frequency) is of fundamental importance in effective
      dosage.

PMID- 18069028
TI  - Chorea in a 29-year-old Nigerian following antimalarial treatment with
      artesunate.

PMID- 18069029
TI  - Coronary in-stent restenosis in diabetic patients after implantation of sirolimus
      or paclitaxel drug-eluting coronary stents.
AB  - It is now emerging that, in patients who are at high risk for cardiovascular
      complications and, in particular, those with diabetes, the occurrence of late
      restenosis and thrombosis after treatment of coronary artery disease with drug
      eluting stents is higher than earlier reports have suggested. Therefore, the aim
      of this study was to assess the prevalence of in-stent restenosis in a cohort of
      consecutive patients with diabetes treated for coronary disease in 2005 with drug
      eluting stents [either sirolimus (58%) or paclitaxel (42%)]. The duration of
      follow-up was 9.0+/-3.4 months [mean+/-1 standard deviation (S.D.)]. A total of
      154 patients (type 2 diabetes: 91%) were included in the study (age: 66+/-10
      years), and the total number of implanted stents was 184. Two subjects died from
      cardiac causes, while myocardial infarction and (un)stable angina were observed
      in 3 (2%) and 39 (25%) patients, respectively. In-stent restenosis, appraised by
      angiography, was observed in 17 individuals (11%) after a mean follow-up of five
      months. Mean HbA(1c) in patients with restenosis was 7.6+/-1.8%. There was no
      difference in the rate of restenosis with sirolimus-(n=8) compared with
      paclitaxel-(n=9) eluting stents. Male gender, oral therapy for diabetes and stent
      diameter were predictors of in-stent restenosis. In conclusion, even over a
      medium-term period, in-stent restenosis remains a potential risk for coronary
      diabetic patients treated with drug-eluting devices.

PMID- 18069030
TI  - Adiponectin: an update.
AB  - The discoveries of leptin and adiponectin were breakthroughs in the field of
      metabolic diseases. Adipose cells produce both proteins and release them into the
      circulation. Leptin acts as a fundamental signal for the brain to modulate food
      intake as a function of energy status. Loss of leptin function results in
      obesity. Although a biological role for adiponectin has not been firmly
      established, clinical and experimental observations indicate that low plasma
      levels contribute to the pathogenesis of insulin resistance, type 2 diabetes and
      cardiovascular diseases in obese or overweight patients. Adiponectin circulates
      as several multimeric species, including a high-molecular-weight form thought to
      be the most clinically relevant. Adiponectin exerts anti-atherogenic effects by
      targeting vascular endothelial cells and macrophages and insulin-sensitizing
      effects, mainly predominantly in muscle and liver. The best-characterized
      molecular mechanism mediating adiponectin's metabolic and vascular activities
      involved stimulation of AMP kinase activity. Adiponectin signaling pathways
      comprise at least two putative receptors (AdipoR1 and AdipoR2). Ways to enhance
      adiponectin bioactivity are actively being sought. In obesity, reducing chronic
      adipose-tissue inflammation and macrophage infiltration into it could be
      beneficial to reverse downregulation of adiponectin gene expression by pro
      inflammatory cytokines. Pharmacologically, thiazolidinediones and cannabinoid-1
      receptor blockers (e.g., rimonabant) increase plasma adiponectin and gene
      expression in adipocytes. Finally, AdipoR activation to mimic adiponectin actions
      could prove beneficial to reduce metabolic risk factors in conditions, such as
      obesity, where low adiponectinemia prevails.

PMID- 18069031
TI  - A standardized protocol to achieve normoglycaemia during labour and delivery in
      women with type 1 diabetes.
AB  - AIM: To evaluate a standardized protocol for maintaining near-normoglycaemia
      during labour and delivery in women with type 1 diabetes. METHODS: Over a nine
      year period (1997-2005), 229 pregnancies in 174 women with type 1 diabetes were
      delivered at one centre. The same regimen was used for the induction of labour
      (group 1) and in women admitted in spontaneous labour (group 2): 10% dextrose
      (80ml/h) intravenous was given along with short-acting insulin, starting at 1IU/h
      intravenous via an infusion pump. Capillary blood glucose (CBG) was determined
      hourly, and the insulin infusion rate was modified accordingly. RESULTS: Labour
      was induced in 85 cases (37%) and spontaneous in 23 cases (10%), and an elective
      C-section was performed in 121 cases (53%). Maternal glycaemia during labour was
      6.1+/-1.6 (range: 3.9-9.2)mmol/l in group 1, and 6.9+/-2.0 (range: 4.7
      12.0)mmol/l in group 2. Maternal glycaemia at delivery was 5.8+/-1.5 (range: 3.4
      9.4) and 6.3+/-1.9 (range: 4.1-11.4)mmol/l in groups 1 and 2, respectively. Women
      who underwent an elective C-section were not included in the standardized
      protocol and had higher glycaemia at delivery 7.1+/-2.0 (range: 2.7-13.5)mmol/l.
      Neonatal hypoglycaemia occurred in 30 infants (13%), and was only associated with
      preterm delivery. CONCLUSION: Using a standardized simple protocol during labour,
      maternal glycaemia was maintained within a near-normal range in 80-85% of cases.

PMID- 18069032
TI  - Outer membrane protein UspA1 and lipooligosaccharide are involved in invasion of
      human epithelial cells by Moraxella catarrhalis.
AB  - Invasion of non-professional phagocytes is a strategy employed by several mucosal
      pathogens, but has not been investigated in detail for Moraxella catarrhalis, a
      major cause of human respiratory tract infections. We investigated the role of
      outer membrane protein (OMP) UspA1 and lipooligosaccharide (LOS) in M.
      catarrhalis invasion into epithelial cells. An isogenic mutant of strain O35E,
      which lacked expression of the UspA1 adhesin, demonstrated not only severely
      impaired adherence (86%) to but also reduced invasion (77%) into Chang
      conjunctival cells in comparison with the wild-type strain. The isogenic, LOS
      deficient mutant strain O35E.lpxA was attenuated in adherence (93%) and its
      capacity to invade was severely reduced (95%), but not abolished. Inhibition
      assays using sucrose and cytochalasin D, respectively, demonstrated that clathrin
      and actin polymerization contribute to internalization of M. catarrhalis by Chang
      cells. Furthermore, inhibition of UspA1-mediated binding to cell-associated
      fibronectin and alpha5beta1 integrin decreased invasion of M. catarrhalis strain
      O35E (72% and 41%, respectively). These data indicate that OMP UspA1 and LOS
      profoundly affect the capacity of M. catarrhalis to invade epithelial cells.

PMID- 18069033
TI  - Identification of a novel Haemophilus influenzae protein important for adhesion
      to epithelial cells.
AB  - Non-typable Haemophilus influenzae (NTHi) is an important human-specific
      respiratory pathogen colonizing the mucosa of the upper respiratory tract. The
      bacterium is a common cause of acute otitis media in children and exacerbations
      in patients with chronic obstructive pulmonary disease (COPD). An immunoglobulin
      (Ig) D-lambda myeloma protein was found to detect a 16 kDa surface protein that
      we designated protein E (PE). The pe gene was cloned using an NTHi genomic DNA
      library, and a truncated PE-derived protein lacking the endogenous signal peptide
      (PE22-160) was synthesized and produced in large amounts in Escherichia coli.
      Interestingly, PE was expressed at the bacterial surface of NTHi as revealed by
      flow cytometry using the IgD-lambda myeloma protein or PE-specific polyclonal
      antibodies. A PE-deficient NTHi mutant was produced and lost 50% of its adhesive
      capacity as compared to the wild-type counterpart when analysed for adhesion to
      type II lung alveolar epithelial cells. In parallel, E. coli expressing full
      length PE1-160 adhered significantly more efficiently to epithelial cells as
      compared to wild-type E. coli. Recombinant IgD that recognized the chemical
      dansyl-chloride did not interact with PE indicating that the IgD-lambda myeloma
      protein most likely was an antibody directed against the H. influenzae surface
      epitope. In conclusion, we have discovered a novel NTHi outer membrane protein
      with adhesive properties using an IgD-myeloma protein.

PMID- 18069034
TI  - Chlamydia trachomatis can protect host cells against apoptosis in the absence of
      cellular Inhibitor of Apoptosis Proteins and Mcl-1.
AB  - Infection with Chlamydia protects mammalian host cells against apoptosis.
      Hypotheses have been proposed to explain this molecularly, including the up
      regulation of host anti-apoptotic proteins such as cellular Inhibitor of
      Apoptosis Protein (IAP) 2 and the Bcl-2 protein Mcl-1. To test for the importance
      of these proteins, we used mouse embryonic fibroblasts from gene-targeted mice
      that were deficient in cIAP1, cIAP2, cIAP1/cIAP2, XIAP, or Mcl-1. Infection with
      Chlamydia trachomatis protected all cells equally well against apoptosis, which
      was induced either with tumour necrosis factor/cycloheximide (IAP-knock-out
      cells) or staurosporine (Mcl-1-knock-out). Therefore, these cellular anti
      apoptotic proteins are not essential for apoptosis-protection by C. trachomatis.

PMID- 18069035
TI  - Pneumatosis cystoides intestinalis in systemic sclerosis.

PMID- 18069036
TI  - Treatment preference for monthly oral ibandronate and weekly oral alendronate in
      women with postmenopausal osteoporosis: A randomized, crossover study (BALTO II).
AB  - OBJECTIVES: Patient preference strongly influences long-term medication use in
      chronic diseases such as postmenopausal osteoporosis. METHODS: This 6-month, open
      label, crossover, international study randomized 350 women with postmenopausal
      osteoporosis to monthly oral ibandronate 150mg for 3months followed by weekly
      alendronate 70mg for 12weeks, or vice versa. RESULTS: Of patients expressing a
      preference (93.1%), more preferred the monthly ibandronate regimen (70.6%) than
      the weekly alendronate regimen (29.4%). The monthly ibandronate preference rate
      was statistically significant (P<0.0001). The most common reasons for ibandronate
      preference were ease of staying on treatment long-term (81.5%) and better
      lifestyle fit (75.4%). More women found the monthly ibandronate regimen more
      convenient (76.6%) than the weekly alendronate regimen (23.4%). The monthly
      ibandronate convenience rate was statistically significant (P<0.0001). The safety
      profiles of the two regimens were similar. CONCLUSION: The strong patient
      preference for monthly ibandronate over weekly alendronate replicates previous
      study findings and may lead to improved treatment adherence in women with
      postmenopausal osteoporosis.

PMID- 18069037
TI  - Unexplained polyarthralgia and celiac disease.
AB  - Celiac disease is an immunological disorder whose best-known manifestations are
      gastrointestinal symptoms. However, early joint manifestations are common and
      frequently overlooked features of celiac disease. We report a case in which
      unexplained inflammatory polyarthralgia and iron-deficiency anemia led to the
      diagnosis of celiac disease. Autoimmune thyroiditis was also a feature. Early
      diagnosis and treatment of celiac disease protect patients against complications
      such as digestive neoplasis. A simple and rapid tool for achieving the early
      diagnosis is the measurement of the serum of anti-gliadin, anti-endomysial and
      anti-tissue transglutaminase antibodies. However, a duodenal biopsy remains the
      only means of making the definitive diagnosis of celiac disease.

PMID- 18069038
TI  - Delivery by shock waves of active principle embedded in gelatin-based capsules.
AB  - PURPOSE: Delivering a drug close to the targeted cells improves its benefit
      versus risk ratio. A possible method for local drug delivery is to encapsulate
      the drug into solid microscopic carriers and to release it by ultrasound. The
      objective of this work was to use shock waves for delivering a molecule loaded in
      polymeric microcapsules. MATERIAL AND METHODS: Ethyl benzoate (EBZ) was
      encapsulated in spherical gelatin shells by complex coacervation. A
      piezocomposite shock wave generator (120 mm in diameter, focused at 97 mm, pulse
      length 1.4 micros) was used for sonicating the capsules and delivering the
      molecule. Shock parameters (acoustic pressure, number of shocks and shock
      repetition frequency) were varied in order to measure their influence on EBZ
      release. A cavitation-inhibitor liquid (Ablasonic) was then used to evaluate the
      role of cavitation in the capsule disruption. RESULTS: The measurements showed
      that the mean quantity of released EBZ was proportional to the acoustic pressure
      of the shock wave (r2 > 0.99), and increased with the number of applied shocks.
      Up to 88% of encapsulated EBZ could be released within 4 min only (240 shocks, 1
      Hz). However, the quantity of released EBZ dropped at high shock rates (above
      2Hz). Ultrasound imaging sequences showed that cavitation clouds might form, at
      high shock rates, along the acoustic axis making the exposure inefficient.
      Measurements done in Ablasonic showed that cavitation plays a major role in
      microcapsules disruption. CONCLUSIONS: In this study, we designed polymeric
      capsules that can be disrupted by shock waves. This type of microcapsule is
      theoretically a suitable vehicle for carrying hydrophobic drugs. Following these
      positive results, encapsulation of drugs is considered for further medical
      applications.

PMID- 18069039
TI  - Colloidal silver fabrication using the spark discharge system and its
      antimicrobial effect on Staphylococcus aureus.
AB  - Nanoscale techniques for silver production may assist the resurgence of the
      medical use of silver, especially given that pathogens are showing increasing
      resistance to antibiotics. Traditional chemical synthesis methods for colloidal
      silver (CS) may lead to the presence of toxic chemical species or chemical
      residues, which may inhibit the effectiveness of CS as an antibacterial agent. To
      counter these problems a spark discharge system (SDS) was used to fabricate a
      suspension of colloidal silver in deionized water with no added chemical
      surfactants. SDS-CS contains both metallic silver nanoparticles (Ag(0)) and ionic
      silver forms (Ag(+)). The antimicrobial affect of SDS-CS on Staphylococcus aureus
      was studied. The results show that CS solutions with an ionic silver
      concentration of 30 ppm or higher are strong enough to destroy S. aureus. In
      addition, it was found that a solution's antimicrobial potency is directly
      related to its level of silver ion concentration.

PMID- 18069040
TI  - Detrimental effect of oxidized LDL on endothelial arginine metabolism and
      transportation.
AB  - The action of oxidatively modified low-density lipoprotein on vascular
      endothelial cells has been proposed to be a crucial process leading to
      endothelial dysfunction and atherogenesis. However, the biochemical mechanism for
      such action is not clear. We have previously shown that arginine uptake and
      metabolism are major determinants of endothelial function in heart failure and
      hypertension. In the present study we therefore aimed to assess the effects of
      oxidized LDL, a major pro-atherogenic molecule, on endothelial l-arginine
      metabolism and its uptake. Endothelial cells were exposed to oxidized LDL or
      native LDL for 24h, and the resultant effects on (1) the intracellular content of
      arginine and its major metabolites including citrulline, N(G)-hydroxy-l-arginine,
      asymmetric dimethylarginine, symmetric dimethylarginine and ornithine, (2) [3H]-l
      arginine uptake and, (3) the pattern of distribution of cationic amino acid
      transporter 1, the principal l-arginine transporter, by confocal microscopy.
      Oxidized LDL (100 microg/mL) reduced intracellular arginine and N(G)-hydroxy-l
      arginine contents by 56 and 71% (P<0.05), respectively, with a concomitant 205%
      increase in ADMA (P<0.05). In conjunction, oxidized LDL reduced endothelial
      uptake of [3H]-arginine by 60%. Furthermore, incubation of endothelial cells with
      oxLDL led to internalization of cationic amino acid transporter 1. We demonstrate
      a novel mechanism, reduced l-arginine transport, by which oxidized LDL impairs
      the ability of the endothelium to generate nitric oxide.

PMID- 18069041
TI  - Steroidogenesis in BeWo cells: role of protein kinase A and benzodiazepines.
AB  - The peripheral benzodiazepine receptor and protein kinase A have been proposed to
      modulate placental steroidogenesis. Binding of the radioactive benzodiazepine PK
      11195 has been observed in membranes isolated from whole human placenta, but the
      presence of the peripheral benzodiazepine receptors, now called translocator
      protein, does not seem to be indispensable. We hypothesized that cAMP analogs
      could induce the translocator protein expression in BeWo cells increasing
      steroidogenesis in the presence of benzodiazepines. The effect of two
      benzodiazepines and of 8-Br-cAMP on steroidogenesis in BeWo cells or in isolated
      human placental mitochondria was studied. Benzodiazepines did not modify
      progesterone synthesis in either system. Progesterone increased three times in
      BeWo cells incubated in the presence of 8-Br-cAMP. The translocator protein was
      not identified by western blot in mitochondria isolated from either the human
      placenta or BeWo cells but it was present in isolated rat testicular
      mitochondria. Neither was it observed in isolated mitochondria from BeWo cells
      incubated with 8-Br-cAMP. An inhibitor of protein kinase A activity, H89, at 25
      microM inhibited 90% the steroidogenesis in BeWo cells, even in the presence of 8
      Br-cAMP, but protein phosphorylation in mitochondria increased in the presence of
      H89, suggesting that protein kinase A modulates the phosphorylation cycle of
      mitochondrial proteins. The results suggest that placental steroidogenesis is
      regulated via activation of protein kinase A modulated by cAMP.

PMID- 18069042
TI  - Two C-terminal peptides of human CKLF1 interact with the chemokine receptor CCR4.
AB  - Human chemokine-like factor 1 (CKLF1) exhibits chemotactic effects on leukocytes.
      A previous study demonstrated that CKLF1 is a functional ligand for human CC
      chemokine receptor 4 (CCR4). In this study, N-terminal amino acid sequencing of
      secreted CKLF1 protein showed that it contains at least two peptides, C27 and
      C19. To examine whether C27 or C19 play a role via CCR4, C27 and C19 were
      chemically synthesized and analyzed by chemotaxis, calcium mobilization, and
      receptor internalization assays in CCR4-tranfected HEK293 cells or Hut78 cells.
      The chemotaxis assay showed that C27 could induce chemotaxis to CCR4-transfected
      HEK293 cells or Hut78 cells while C19 had weaker chemotactic activity, especially
      in Hut78 cells. C27- or C19-induced chemotaxis was abolished by pertussis toxin,
      suggesting the involvement of a Gi/o pathway. C27- or C19-induced chemotaxis was
      also inhibited by an antagonist of CCR4 that show good binding potency, excellent
      chemotaxis inhibitory activity and selectivity toward CCR4, suggesting that their
      chemotactic activity specifically involved CCR4. The chemotactic response of CCR4
      tranfected HEK293 cells to C27 or C19 was markedly inhibited by preincubation
      with TARC/CCL17. TARC/CCL17 effectively desensitized the calcium mobilization
      induced by C27 or C19. Similarly, both of C27 or C19 also desensitized the
      calcium mobilization and chemotaxis of CCR4-tranfected HEK293 cells in response
      to TARC/CCL17, suggesting that they might interact with a common receptor. Both
      C27- and C19-induced clear internalization of CCR4-EGFP. These results confirm
      that the secreted peptides of CKLF1, C27 and C19, have functional activation via
      CCR4.

PMID- 18069043
TI  - Eukaryotic initiation factor 4E.
AB  - Eukaryotic translation initiation factor 4E (eIF4E) is perhaps best known for its
      function in the initiation of protein synthesis on capped mRNAs in the cytoplasm.
      However, recent studies have highlighted that eIF4E has many additional
      functions, which include the nuclear export of specific mRNAs as well as roles in
      ageing and the translation of some uncapped viral RNAs. This review aims to
      update the reader on recent developments, including the potential of eIF4E as a
      therapeutic target.

PMID- 18069044
TI  - Preventing facial recognition when rendering MR images of the head in three
      dimensions.
AB  - In the United States it is not allowed to make public any patient-specific
      information without the patient's consent. This ruling has led to difficulty for
      those interested in sharing three-dimensional (3D) images of the head and brain
      since a patient's face might be recognized from a 3D rendering of the skin
      surface. Approaches employed to date have included brain stripping and total
      removal of the face anterior to a cut plane, each of which lose potentially
      important anatomical information about the skull surface, air sinuses, and
      orbits. This paper describes a new approach that involves (a) definition of a
      plane anterior to which the face lies, and (b) an adjustable level of deformation
      of the skin surface anterior to that plane. On the basis of a user performance
      study using forced choices, we conclude that approximately 30% of individuals are
      at risk of recognition from 3D renderings of unaltered images and that truncation
      of the face below the level of the nose does not preclude facial recognition.
      Removal of the face anterior to a cut plane may interfere with accurate
      registration and may delete important anatomical information. Our new method
      alters little of the underlying anatomy and does not prevent effective
      registration into a common coordinate system. Although the methods presented here
      were not fully effective (one subject was consistently recognized under the
      forced choice study design even at the maximum deformation level employed) this
      paper may point a way toward solution of a difficult problem that has received
      little attention in the literature.

PMID- 18069045
TI  - Serotoninergic regulation of emotional and behavioural control processes.
AB  - 5-Hydroxytryptamine (5-HT, serotonin) has long been implicated in a wide variety
      of emotional, cognitive and behavioural control processes. However, its precise
      contribution is still not well understood. Depletion of 5-HT enhances behavioural
      and brain responsiveness to punishment or other aversive signals, while
      disinhibiting previously rewarded but now punished behaviours. Findings suggest
      that 5-HT modulates the impact of punishment-related signals on learning and
      emotion (aversion), but also promotes response inhibition. Exaggerated aversive
      processing and deficient response inhibition could underlie distinct symptoms of
      a range of affective disorders, namely stress- or threat-vulnerability and
      compulsive behaviour, respectively. We review evidence from studies with human
      volunteers and experimental animals that begins to elucidate the neurobiological
      systems underlying these different effects.

PMID- 18069046
TI  - Memory search and the neural representation of context.
AB  - A challenge for theories of episodic memory is to determine how we focus memory
      search on a set of recently learned items. Cognitive theories suggest that the
      recall of an item representation is driven by an internally maintained context
      representation that integrates incoming information with a long time-scale.
      Neural investigations have shown that recalling an item revives the pattern of
      brain activity present during its study. To link these neural and cognitive
      approaches, we propose a framework in which context is maintained and updated in
      prefrontal cortex, and is associated with item information through hippocampal
      projections. The proposed framework is broadly consistent with neurobiological
      studies of temporal integration and with studies of memory deficits in
      individuals with prefrontal damage.

PMID- 18069047
TI  - Live-imaging stem-cell homeostasis in the Arabidopsis shoot apex.
AB  - A precise spatio-temporal regulation of growth and differentiation is crucial to
      maintain a stable population of stem cells in the shoot apical meristems (SAMs)
      of higher plants. The real-time and simultaneous observations of dynamics of cell
      identity transitions, growth patterns, and signaling machinery involved in cell
      cell communication is crucial to gain a mechanistic view of stem-cell
      homeostasis. In this article, I review recent advances in understanding the
      regulatory dynamics of stem-cell maintenance in Arabidopsis thaliana and discuss
      future challenges involved in transforming the static maps of genetic
      interactions into a dynamic framework representing functional molecular and
      cellular interactions in living SAMs.

PMID- 18069048
TI  - The detection and assessment of the aneugenic potential of selected oestrogens,
      progestins and androgens using the in vitro cytokinesis blocked micronucleus
      assay.
AB  - The use of 17-beta-oestradiol, testosterone, progesterone, zearanol, trenbolone
      acetate and melengesterol acetate in animal feed as growth promoters has been
      banned in the European Union since 1989. However, the data available on their
      genotoxicity is limited. To bridge this gap the present study was carried out
      with the aim of evaluating these hormones for their ability to induce aneuploidy.
      Aneuploidy has been recently considered sufficiently important to be included in
      the routine testing of chemicals and radiation. These types of numerical
      chromosomal aberrations may arise by at least two mechanisms, chromosome loss and
      non-disjunction. Over the past few years, the cytokinesis blocked micronucleus
      (CBMN) technique has evolved into a robust assay for the detection of aneuploidy
      induction. At the present time, it is the only assay which can reliably detect
      both chromosome loss and non-disjunction when the basic methodology is coupled
      with appropriate molecular probing techniques such as immunoflourescent labelling
      of kinetochores and Fluorescence in situ Hybridisation. In this present study,
      aneuploidy induction by three groups of hormones was studied using CBMN assay
      coupled with Fluorescence in situ Hybridisation. The results from the present
      study demonstrate that 17-beta-oestradiol, diethylstilboestrol, progesterone and
      testosterone are genotoxic and induce aneuploidy by non-disjunctional mechanism,
      whereas trenbolone is also genotoxic by a clastogenic mechanism. However,
      melengesterol acetate and zearanol proved to be non-genotoxic in vitro.

PMID- 18069049
TI  - The chemotherapeutic agents nocodazole and amsacrine cause meiotic delay and non
      disjunction in spermatocytes of mice.
AB  - Aneuploidy of germ cells contributes to reduced fertility, foetal wastage and
      genetic defects. The possible risk of aneuploidy induction by the cancer
      chemotherapeutic drugs amsacrine (AMSA) and nocodazole (NOC) was investigated in
      male mice. Two molecular cytogenetic approaches were used: (1) the BrdU
      incorporation assay to test the altered duration of meiotic divisions and (2) the
      sperm-FISH assay to determine aneuploidy induction during meiosis by observing
      hyperhaploid and diploid sperm. Sperm were sampled from the Caudae epididymes of
      treated and solvent control males. Single intraperitoneal injections with NOC (35
      mg/kg) and AMSA (15 mg/kg) caused a meiotic delay of 24h. The timing of sperm
      sampling for the sperm-FISH assay was adjusted accordingly, i.e. 23 days after
      treatment. Mice were treated with 18, 35 and 50 mg/kg of NOC, or 5, 10, 15 and 20
      mg/kg of AMSA. Significant dose-dependent increases above the concurrent controls
      in the frequencies of hyperhaploid sperm were found with both agents. Significant
      increases in the frequencies of diploid sperm were found only with AMSA. These
      results provide a basis for genetic counselling of patients under AMSA or NOC
      chemotherapy. During a period of 3-4 months after the end of chemotherapy, they
      may stand a higher risk of siring chromosomally abnormal offspring.

PMID- 18069050
TI  - DNA damage induced by genotoxicants in zebrafish (Danio rerio) embryos after
      contact exposure to freeze-dried sediment and sediment extracts from Laguna Lake
      (The Philippines) as measured by the comet assay.
AB  - Laguna Lake, Philippines, is utilised as a resource for drinking and irrigation
      water and a major source of animal protein for more than 11 million residents.
      However, it also serves as a huge sink for anthropogenic pollutants from a
      variety of direct or indirect discharges. Given their well-known properties to
      accumulate organic pollutants, Lake Laguna sediments have been investigated by
      use of a newly developed sediment-contact assay to determine the bioavailable
      fraction of the total genotoxic hazard potential. Freshly fertilized zebrafish
      eggs (2 h after fertilization) were allowed to develop while exposed to different
      concentrations of freeze-dried sediments (exposure to bioavailable compounds) as
      well as organic extracts (complete genotoxic hazard potential including
      bioaccumulation) prepared from sediments collected at five sites within the lake.
      Following a 96 h exposure, single-cell suspensions were prepared from macerated
      larvae and analyzed for DNA strand-breaks by use of the comet assay. Genotoxicity
      could be identified in both solid-phase exposure scenarios as well as after
      exposure to organic sediment extracts. Only the South Bay (SB) site did not show
      a significant genotoxic burden relative to controls in tests of both freeze-dried
      sediment and organic extracts. In contrast, the Northwest Bay site displayed
      pronounced genotoxicity to the zebrafish embryos in both exposure scenarios.
      Perylene and copper in the sediments could be identified as potential causes of
      the genotoxic response. To compare the results (maximum induction coefficients)
      of zebrafish embryos with an established comet protocol, rainbow trout liver
      cells (RTL-W1) were exposed to the same extracts. The findings correlated well
      (Spearman correlation r=0.90), proving a good reliability of the results from
      zebrafish primary cells. In conclusion, the present study demonstrates that the
      bioavailable fraction of the genotoxic pollutants may pose a threat for both
      benthic organisms and human health via drinking-water and fish consumption.

PMID- 18069051
TI  - Trichlorfon effects on mouse oocytes following in vivo exposure.
AB  - Trichlorfon (TCF) is a widely used pesticide, which according to some
      epidemiological and experimental data, is suspected of being aneugenic in human
      and mouse cells. In particular, in vitro studies in mouse oocytes showed the
      induction of aneuploidy and polyploidy at the first meiotic division and of
      severe morphological alterations of the second meiotic spindle. We have tested
      the hypothesis that an acute treatment of mice with TCF might similarly affect
      chromosome segregation in maturing oocytes. Superovulated MF-1 mice were
      intraperitoneally injected with 400mg/kg TCF or orally administered with 600mg/kg
      TCF either at the time of or 4h after human chorionic gonadotrophin (HCG)
      injection. Oocytes were harvested 17h after HCG and metaphase II chromosomes were
      cytogenetically analyzed. No significant increase of aneuploid or polyploid cells
      was detected at any treatment condition. A significant (p<0.001) decrease of
      metaphases showing premature chromatid separation or premature anaphase II in all
      TCF-treated groups with respect to controls suggested that TCF treatment may have
      delayed the first meiotic division. To evaluate possible effects of the pesticide
      upon the second meiotic division, a group of females orally treated with 600mg/kg
      TCF at resumption of meiosis was mated with untreated males and zygotes were
      collected for cytogenetic analysis. No evidence of aneuploidy induction was
      obtained, but the frequency of polyploid zygotes was increased fivefold over the
      control level (p<0.01). Such polyploid embryos might have arisen from
      fertilization of oocytes that were either meiotically delayed and still in
      metaphase I at fertilization or progressed through anaphase II without
      cytokinesis. These findings show that in vivo studies on aneuploidy induction in
      oocytes may yield results different from those obtained by in vitro experiments
      and that both kinds of data may be necessary for risk assessment of
      environmentally relevant exposures.

PMID- 18069052
TI  - Synthesis of 1,5-bis(4,6-dichloro-1,3,5-triazinylamino)naphthalene and its
      application to spectrofluorimetric determination of aniline.
AB  - A new fluorescent reagent 1,5-bis(4,6-dichloro-1,3,5-triazinylamino)naphthalene
      (DTAN) was synthesized. The optimum conditions of fluorescent reaction of this
      reagent with aniline (PA) were also investigated. Based on this reaction, a new
      spectrofluorimetric method was developed for the determination of aniline. The
      fluorescent intensity was directly proportional to the concentration of aniline
      in the ranges 0.05-2.0 microg mL(-1) and 2.0-50 microg mL(-1) with the detection
      limits of 34 ng mL(-1) and 90 ng mL(-1). This method is simple, practical and can
      afford good precision and accuracy and can be successfully applied to assess
      aniline in water samples. A possible mechanism of the change of fluorescence
      intensity introduced by putting the aniline into the system is also discussed.

PMID- 18069053
TI  - Application of ruthenium catalyzed oxidation of [tris(2-aminoethyl)amine] in
      trace determination of ruthenium in environmental water samples.
AB  - The ruthenium catalyzed oxidation of tris(2-aminoethyl)amine (TREN) by
      hexacyanoferrate(III) has been utilized for the development of a new and
      sensitive catalytic kinetic method (CKM) for the determination of ruthenium(III).
      The reaction was followed spectrophotometrically by the decrease in absorbance at
      420 nm (lambda(max) of [Fe(CN)6]3-). The CKM developed utilizes fixed time
      procedure under optimum reaction conditions where the change in absorbance
      (DeltaAt) versus ruthenium(III) concentrations is plotted. The calibration curve
      recommended for the method is linear in the concentration range 10.11-252.67 ng
      ml(-1) with very good accuracy and reproducibility and a maximum error 2.20%. The
      detection limits of the method for ruthenium(III) corresponding to 10, 15 and 20
      min are 8.02, 5.03 and 3.15 ng ml(-1), respectively. The ruthenium(III) has also
      been determined in the presence of several other interfering and non-interfering
      cations and anions and no foreign ions interfered in the determination of
      ruthenium(III) up to five-fold higher concentration of the foreign ions tested.
      The method is highly sensitive, selective and stable. It has successfully been
      applied for the determination of trace ruthenium(III) in some synthetic and
      environmental water samples. A review of most of the published catalytic kinetic
      and some other important methods for the determination of ruthenium has also been
      presented.

PMID- 18069054
TI  - Human bocavirus commonly involved in multiple viral airway infections.
AB  - BACKGROUND: Human bocavirus (HBoV) was recently discovered in children with acute
      respiratory tract infections. We have included a PCR for HBoV in a study on
      airway infections in children. OBJECTIVES: To study the occurrence of HBoV in
      Norwegian children, and to evaluate the results of a semiquantitative PCR. STUDY
      DESIGN: During a 4-month period in the winter season 2006/2007 we collected
      nasopharyngeal aspirations from children who were admitted to the Department of
      Pediatrics. All samples were examined for 17 agents with real-time PCR. RESULTS:
      HBoV was detected in 45 of 376 samples (12%). The occurrence of HBoV was stable
      during the study period. Multiple viral infections were present in 78% of the
      samples (42% double, 20% triple and 16% quadruple infections). RS-virus,
      enterovirus and human metapneumovirus were the most frequently codetected agents.
      In samples with a high load for HBoV, significantly fewer multiple infections
      were found than in the other samples. Eighty-eight percent of the 25 patients
      with HBoV recorded as either the only or the dominating virus, and 50% of the
      other patients, had lower respiratory tract infection. The difference was
      statistically significant. CONCLUSIONS: HBoV was frequently detected in
      nasopharyngeal aspirates from children with airway infections in Norway. Multiple
      viral infections were common among the HBoV-infected patients. Semiquantitative
      PCR results may be useful for interpretation of clinical relevance.

PMID- 18069055
TI  - Dual infections by influenza A/H3N2 and B viruses and by influenza A/H3N2 and
      A/H1N1 viruses during winter 2007, Corsica Island, France.
AB  - BACKGROUND: The investigation of dual influenza infection human cases is of major
      interest specifically for the control of new emerging influenza strains.
      OBJECTIVES: Using RT-PCR assays, we retrospectively assessed the prevalence of
      dual influenza virus infections that occurred in patients during the 2006-2007
      winter season in Corsica Island (France). STUDY DESIGN: One hundred and thirty
      four nasal swabbing samples taken from patients suffering from influenza-like
      illness between February and March 2007 were analysed using a rapid influenza
      antigen detection test, cell culture and RT-PCR assays. RESULTS AND CONCLUSION:
      Influenza viruses were detected in 93 (69.4%) of 134 patients with influenza-like
      illness using the combination of classical and molecular assays. Dual respiratory
      infections by influenza viruses were detected in 3 (3.2%) of the 93 influenza
      positive patients, including two cases of infection by influenza A/H3N2 and B
      viruses and one case of dual infection by influenza A/H3N2 and A/H1N1 viruses. In
      the present report, human co-infection cases by two influenza viruses appeared as
      a rare event in symptomatic patients. However, the virological and
      epidemiological mechanisms that determine the occurrence of dual influenza
      infections remain to be fully investigated in further prospective multicentric
      studies.

PMID- 18069057
TI  - HCV genotype 5: epidemiology and spread of an uncommon genotype.

PMID- 18069056
TI  - Modulation of natural killer cells by human cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) causes lifelong, persistent infections and its
      survival is under intense, continuous selective pressure from the immune system.
      A key aspect of HCMV's capacity for survival lies in immune avoidance. In this
      context, cells undergoing productive infection exhibit remarkable resistance to
      natural killer (NK) cell-mediated cytolysis in vitro. To date, six genes encoding
      proteins (UL16, UL18, UL40, UL83, UL141 and UL142) and one encoding a microRNA
      (miR-UL112) have been identified as capable of suppressing NK cell recognition.
      Even though HCMV infection efficiently activates expression of ligands for the NK
      cell activating receptor NKG2D, at least three functions (UL16, UL142 and miR
      UL112) act in concert to suppress presentation of these ligands on the cell
      surface. Although HCMV downregulates expression of endogenous MHC-I, it encodes
      an MHC-I homologue (UL18) and also upregulates the expression of cellular HLA-E
      through the action of UL40. The disruption of normal intercellular connections
      exposes ligands for NK cell activating receptors on the cell surface, notably
      CD155. HCMV overcomes this vulnerability by encoding a function (UL141) that acts
      post-translationally to suppress cell surface expression of CD155. The mechanisms
      by which HCMV systematically evades (or, more properly, modulates) NK cell
      recognition constitutes an area of growing understanding that is enhancing our
      appreciation of the basic mechanisms of NK cell function in humans.

PMID- 18069058
TI  - Sensitivity of a rapid immuno-chromatographic test for hepatitis C antibodies
      detection.
AB  - BACKGROUND AND OBJECTIVES: Enzyme-linked immunoassays (ELISA) are the most widely
      used anti-hepatitis C virus (HCV) screening tests but simple, instrument and
      electricity-free screening tests have been developed with results available in a
      few minutes. METHODS: The sensitivity of a rapid immuno-chromatographic assay for
      the detection of anti-HCV antibodies was evaluated on 421 HCV RNA-positive
      samples from chronic carriers and compared with ELISA method. RESULTS: The
      sensitivity of the ELISA method was 99.3% and the sensitivity of the rapid test
      was 95.5%. False negative results were independent of HCV genotype, but were
      associated with human immunodeficiency virus (HIV)-positive status. Among HIV
      negative people, sensitivities of the rapid test and the EIA assay were 99.2% and
      100%, respectively. Whereas among HIV-positive people, sensitivities were 77.5%
      and 96.3%. CONCLUSIONS: The immuno-chromatographic test is rapid and simple, and
      could be used along with rapid anti-HIV determination, in settings with limited
      facilities or when rapid results are required.

PMID- 18069059
TI  - Sleeping newborns extract prosody from continuous speech.
AB  - OBJECTIVE: Behavioral experiments show that infants use both prosodic and
      statistical cues in acquiring language. However, it is not yet clear whether
      these prosodic and statistical tools are already present at birth. METHODS: We
      recorded brain responses of sleeping newborns to natural sounds rich in prosody,
      namely singing and continuous speech, and to two impoverished manipulations of
      speech. A total of 11 newborns were presented with continuous speech, singing,
      and degraded speech, while MEG was recorded. RESULTS: We found that a brain
      response elicited to the prosodically rich singing and continuous natural speech
      conditions decreased dramatically when the prosody in the speech was
      impoverished. CONCLUSIONS: We claim that this response is the indicator of the
      infants' sensitivity to prosodic cues in language, which is already present at
      birth during natural sleep. SIGNIFICANCE: The indicators of detection of prosody
      may be crucial in assessing the normal and abnormal cortical function in
      newborns, especially of those infants at-risk for language problems.

PMID- 18069060
TI  - The upper values of plasma creatine kinase of professional soccer players during
      the Brazilian National Championship.
AB  - The current schedule of the Brazilian Soccer Championship may not give players
      enough recovery time between games. This could increase the chances of muscle
      damage and impaired performance. We hypothesized that plasma creatine kinase (CK)
      activity could be a reliable indirect marker of muscle overload in soccer
      players, so we sought to identify the reference values for upper limits of CK
      activity during a real-life elite competition. This study analyzed changes in
      plasma CK activity in 128 professional soccer players at different times during
      the Brazilian Championship. The upper limits of the 97.5th and 90th percentiles
      determined for CK activity were 1.338U/L and 975U/L, respectively, markedly
      higher than values previously reported in the literature. We also evaluated a
      team monthly throughout the Championship. The upper limit of the 90th percentile,
      975U/L, was taken as the decision limit. Six players showing plasma CK values
      higher than this were asked to decrease their training for 1 week. These players
      presented lower CK values afterwards. Only one player with a CK value higher than
      the decision limit (1800U/L 1 day before a game) played on the field and was
      unfortunately injured during the game. The CK activity in all the other players
      showed a significant decrease over the course of the Championship, and the values
      became more homogeneous at the end. The results presented here suggest that
      plasma CK upper limit values can be used as a practical alternative for early
      detection of muscle overload in competing soccer players.

PMID- 18069061
TI  - Mediators of change following a senior school physical activity intervention.
AB  - It has been suggested that the low level of effectiveness of youth interventions
      is due to a lack of knowledge regarding the mechanisms responsible for behaviour
      change. The identification of behaviour mediators is necessary for the
      progression of physical activity research, as it allows researchers to determine
      which components of an intervention are responsible for mediating behaviour
      change. The purpose of this study was to identify mediators of behaviour change
      in a physical activity intervention for senior school students. Participants
      (n=78) were randomly allocated to control or intervention conditions for a period
      of 10 weeks. Moderate-to-vigorous physical activity (MVPA) and potential
      mediators were assessed at baseline and post-intervention (10 weeks).
      Hypothesized mediators were derived from Bandura's Social Cognitive Theory and
      included: peer support, exercise self-efficacy and outcome expectancy. Mediation
      was assessed using the product-of-coefficients test described by MacKinnon and
      colleagues, based on the criteria for mediation identified by Baron and Kenny.
      While none of the variables satisfied all four criteria for mediation among males
      or females, self-efficacy was able to satisfy the first three criteria among
      females in the study. Exercise self-efficacy may be a mediator of physical
      activity behaviour in adolescent girls.

PMID- 18069062
TI  - Surrogate thigh model for assessing impact force attenuation of protective pads.
AB  - A thigh contusion is a common sports related injury that can result in disability
      and time away from activity. Thigh pads can be worn to help reduce injury
      occurrence and severity. To evaluate the relative effectiveness of protective
      guards a thigh model is required. This study utilised data generated from impacts
      on human volunteers and cadaver material to select a surrogate soft tissue
      component for a thigh model. This component was attached to a stainless steel
      beam that represented the femur. The model was instrumented with an internal
      transducer to measure local peak force. This parameter provided a measure of the
      impact force attenuation of protective equipment. Initial tests were conducted on
      cricket thigh pads. The thigh model can be used to assess the relative
      effectiveness of thigh guards and has the potential to determine whether the
      ideally sought lightweight low bulk pads offer similar protection as other
      bulkier pads.

PMID- 18069063
TI  - Improved running economy and increased hemoglobin mass in elite runners after
      extended moderate altitude exposure.
AB  - There is conflicting evidence whether hypoxia improves running economy (RE),
      maximal O(2) uptake (V(O)(2max)), haemoglobin mass (Hb(mass)) and performance,
      and what total accumulated dose is necessary for effective adaptation. The aim of
      this study was to determine the effect of an extended hypoxic exposure on these
      physiological and performance measures. Nine elite middle distance runners were
      randomly assigned to a live high-train low simulated altitude group (ALT) and
      spent 46+/-8 nights (mean+/-S.D.) at 2860+/-41m. A matched control group (CON,
      n=9) lived and trained near sea level ( approximately 600m). ALT decreased
      submaximal V(O)(2) (Lmin(-1)) (-3.2%, 90% confidence intervals, -1.0% to -5.2%,
      p=0.02), increased Hb(mass) (4.9%, 2.3-7.6%, p=0.01), decreased submaximal heart
      rate (-3.1%, -1.8% to -4.4%, p=0.00) and had a trivial increase in V(O)(2max)
      (1.5%, -1.6 to 4.8; p=0.41) compared with CON. There was a trivial correlation
      between change in Hb(mass) and change in V(O)(2max) (r=0.04, p=0.93). Hypoxic
      exposure of approximately 400h was sufficient to improve Hb(mass), a response not
      observed with shorter exposures. Although total O(2) carrying capacity was
      improved, the mechanism(s) to explain the lack of proportionate increase in
      V(O)(2max) were not identified.

PMID- 18069064
TI  - Reactive agility of rugby league players.
AB  - While studies have investigated change of direction speed in rugby league
      players, no study has investigated the reactive agility of these athletes. The
      purpose of this study was to investigate the reactive agility of rugby league
      players, to determine if this quality discriminated higher and lesser skilled
      players. Twenty-four elite (mean+/-S.D. age, 24.5+/-4.2 years) and 42 sub-elite
      (23.6+/-5.3 years) rugby league players completed a game-specific test of
      reactive agility. Elite players had better response accuracy (93.2+/-1.9% vs.
      85.5+/-2.5%; p<0.05, effect size=0.58) and faster decision (89.5+/-5.8ms vs.
      111.5+/-6.4ms; p<0.05, effect size=0.62) and movement times (2.35+/-0.03s vs.
      2.56+/-0.03s; p<0.05, effect size=1.39) on the reactive agility test than sub
      elite players. The reactive agility test was able to distinguish four distinct
      classifications. Specifically, players were classified as requiring either (1)
      decision-making and change of direction speed training to further consolidate
      good physical and perceptual abilities, (2) decision-making training to develop
      below average perceptual abilities, (3) change of direction speed training to
      develop below average physical attributes or (4) a combination of decision-making
      and change of direction speed training to develop below average physical and
      perceptual abilities. The results of this study demonstrate that a test of
      reactive agility discriminates higher and lesser skilled rugby league players. In
      addition, these findings highlight the important contribution of perceptual skill
      to agility in rugby league players.

PMID- 18069065
TI  - Validation of the RT3 in the measurement of physical activity in children.
AB  - The aim of this study was to assess the validity of the RT3 accelerometer, and
      its inbuilt algorithm, in measuring inactivity, walking and running in children.
      Twenty children, aged 7-12 years, participated in the study. The RT3 was compared
      to physiological energy expenditure obtained via a wireless portable
      ergospirometric system. Data analysis was performed using Bland and Altman plots
      and Pearson product moment correlation coefficients. There were no significant
      differences between the methods for each activity. Bland and Altman 95% limits of
      agreement between the two measures in kcalmin(-1) for each of the activities were
      as follows: inactivity (-0.058, 0.47), walking at 3kmh(-1) (-1.22, 0.83) brisk
      walking at 6kmh(-1) (-2.74, 0.54), brisk walking at 6kmh(-1) on an incline of a
      10% gradient (-1.69, 2.11), and jogging at 9kmh(-1) (-3.67, 1.24). Energy
      expenditure via the RT3 correlated significantly with that obtained by indirect
      calorimetry for each activity independently (r=0.56-0.84, all P<0.01). The RT3
      provided a valid estimate of inactivity, walking and running and would thus
      appear appropriate for the objective measurement of physical activity levels.

PMID- 18069066
TI  - Descriptive survey about causes of illness given by the parents of children with
      cancer.
AB  - BACKGROUND: When a doctor diagnoses a child's illness as cancer, parents very
      often react by creating wrong and unrealistic theories about the origins of their
      child's illness which in turn generates self-blame in the parents, who take
      responsibility for the disease. OBJECTIVE: To find what are the parents' beliefs
      about the origins of their children's illness. DESIGN: Descriptive study. SAMPLE:
      Seventy-two couples of parents whose children with cancer are under treatment in
      the haemato-oncology paediatric ward of the Padova hospital. They have been
      collected by a no probabilistic method of sampling. METHODS: A questionnaire was
      used, based on current literature, which investigates the beliefs of the parents
      as to what are the causes of illness, whether the parents research information
      about the illness and the origins of cancer and what are the information sources
      they use in order to establish if there is a connection between these factors.
      RESULTS: Eighty-seven percent of the sample group thinks that there is a specific
      origin of their child's illness: 27% believes the cause is environmental
      pollution, 26% believes it is due to radiation emissions, 26% believes it is due
      to genetic factors and 8% believes it is due to other causes. Eighty six percent
      and 70% of the sample search for information about the illness and its causes;
      64% of the parents state that the first meeting with the medical staff, in which
      the illness is explained and they are informed that there are no known causes
      that produce it, does not clarify their doubts. The sources more often used to
      search for more information and explanations are the physicians in the ward,
      internet and medical books. CONCLUSIONS: This survey confirms the importance of
      an "advocacy" role of the nurse in educating the caregiver and the need to create
      instruments which guide the parents in the informative process and the research
      for good information. Nurses need to be cognizant that their care is crucial not
      just for the child, but for the entire family.

PMID- 18069067
TI  - A critical evaluation of discography in patients with lumbar intervertebral disc
      disease.
AB  - STUDY DESIGN: The study is a prospective observational study of 48 continuous
      patients with symptomatic lumbar degenerative disk disease. Each patient
      underwent discography, MRI, and a biochemical analysis of disk lavage fluid.
      OBJECTIVES: The purpose of this study was to correlate concordant pain on
      discography with MRI grade and biochemical markers of inflammation in a clinical
      setting. SUMMARY OF BACKGROUND DATA: The pathophysiology of degenerative disk
      disease is complex. Discography is used to differentiate symptomatic from
      asymptomatic levels. MRI is used to image changes in disk water content.
      Biochemical assays have identified molecular markers of inflammation. To date, no
      study has correlated concordant pain on discography with MRI findings and
      biochemical markers. METHODS: Forty-eight (48) continuous patients with
      symptomatic lumbar degenerative disk disease gave informed consent for study
      entry. Patient sex, age, insurance, work status and visual analog score (VAS)
      were recorded. MRI was obtained and Pfirrmann grading was performed by a single
      spine surgeon. Discography with disc lavage was performed by a single
      anesthesiologist. Lavage samples were tested for inflammatory markers with high
      resolution multi-plex bead immunoassays and ELISA with >5 pg/ml resolution.
      RESULTS: None of demographic variables was significantly related to concordant
      pain on discogram by chi-squared tests and Mann-Whitney U-test. The Pfirrmann
      score was significantly different for patients with and without concordant pain
      at L3-L4 (p<0.001), but was insignificant at other levels after multitest
      correction. Pfirrmann scores were significantly different at any level in
      patients with and without concordant pain. VAS scores were not significantly
      correlated with opening pressures at any level. Despite the presence of serum
      proteins in the disk lavage fluid, none of the tested inflammatory mediators was
      identified by multi-plex bead immunoassays and ELISA. CONCLUSIONS: There are only
      weak correlations between demographic, discogram, and radiographic variables.
      Response to discogram cannot be predicted by non-invasive means. The disk lavage
      method was unable to identify the presence of specific inflammatory peptides with
      multi-plex immunoassays and ELISA.

PMID- 18069068
TI  - Comparative effects of Artemisia dracunculus, Satureja hortensis and Origanum
      majorana on inhibition of blood platelet adhesion, aggregation and secretion.
AB  - Platelet hyperactivity, resulting in platelet adhesion to the vessel wall, is one
      of the most important factors responsible for thrombosis and the incidence of
      cardiovascular diseases. In this study we were aimed to investigate and compare
      the inhibitory effects of the methanol extracts of three herb species on adhesion
      of the activated platelet to laminin-coated plates, aggregation and protein
      secretion. Artemisia dracunculus (tarragon), Satureja hortensis (summer savory)
      and Origanum majorana (marjoram) are used as blood anti-coagulator in Iranian
      folk medicine. Human platelets were prepared and incubated with different
      concentrations of the test samples (equivalent to 50-200 microg of each of the
      plant leaves powder/mL) for 60 min. The treated and untreated platelets were then
      activated with thrombin (0.25 U/mL) and their adhesion to laminin-coated plates
      was investigated. Based on our observations, the methanol extract of A.
      dracunculus, S. hortensis and O. majorana, at a concentration of 200 microg/mL,
      inhibited platelet adhesion to laminin-coated wells by 51%, 48% and 40%,
      respectively. In addition to alternation of cell adhesive properties, self
      aggregation and protein secretion of the treated platelets were also affected
      upon treatment with the crude methanol extracts. These observations provide the
      basis for the traditional use of these herbs in treatments of cardiovascular
      diseases and thrombosis.

PMID- 18069069
TI  - Intussusception after laparoscopic Roux-en-Y gastric bypass.

PMID- 18069070
TI  - Effect of Roux-en-Y gastric bypass in obese patients with Barrett's esophagus:
      attempts to eliminate duodenogastric reflux.
AB  - BACKGROUND: To assess the effect of Roux-en-Y gastric bypass (RYGB) at a tertiary
      referral Center of Excellence for bariatric surgery on the length and presence of
      dysplasia in morbidly obese patients with Barrett's esophagus (BE). Esophageal
      reflux of gastroduodenal contents (acid, bile) contributes to the development of
      BE and progression in the dysplasia-carcinoma sequence. Obese patients have a
      high prevalence of gastroesophageal reflux and might be at an increased risk of
      developing BE and esophageal adenocarcinoma. The effect of eliminating
      duodenogastroesophageal reflux on BE is not known. METHODS: We performed a
      retrospective review of all patients with pre-existing, biopsy-proven, long
      segment (>3 cm) BE undergoing RYGB at our institution. Only patients with >1 year
      of endoscopic, biopsy-controlled follow-up (mean 34 mo) were included. RESULTS:
      Five patients (3 men and 2 women) were identified. The mean +/- standard error of
      the mean preoperative length of BE was 6 +/- 2 cm; 2 patients had low-grade
      dysplasia and 1 indeterminate dysplasia. At the postoperative follow-up (>1 yr)
      examinations, the length of BE had decreased in 4 patients; the overall length
      was 2 +/- 1 cm; and only 1 patient had dysplasia. All patients experienced a
      decrease in the length of BE (n = 4), complete disappearance of BE (n = 2), or
      improvement in the degree of dysplasia (n = 3). The body mass index had decreased
      from 43 +/- 4 kg/m(2) to 33 +/- 3 kg/m(2), and all experienced subjective
      improvement in reflux symptoms postoperatively. RYGB resulted in complete or
      partial regression of BE in 4 of 5 patients and improvement in reflux symptoms in
      all. CONCLUSION: Our results suggest that RYGB might be the procedure of choice
      in morbidly obese patients with BE requiring surgical treatment for
      gastroesophageal reflux disease.

PMID- 18069071
TI  - Techniques of laparoscopic gastric bypass: on-line survey of American Society for
      Bariatric Surgery practicing surgeons.
AB  - BACKGROUND: Various techniques have been used for laparoscopic gastric bypass.
      This study was performed to survey American Society for Bariatric Surgery
      practicing surgeons on how they perform laparoscopic gastric bypass. METHODS: An
      Internet-based survey was sent to all practicing surgeons in the American Society
      for Bariatric Surgery database by way of e-mail. The survey was divided into
      sections, including experience, pouch, limbs, gastrojejunostomy (GJ),
      jejunojejunostomy, and band. The survey results were collected from the Internet
      site after 4 months. RESULTS: A total of 215 surgeons responded; 98% stated they
      performed laparoscopic gastric bypass. The surgeons had performed an average of
      423 cases in their career and 95 cases during the past 12 months. The average
      pouch size was 25 cm(3) and approximately one half of the surgeons (49%) measured
      the pouch size by the distance for the gastroesophageal junction. Almost all
      surgeons (99.5%) performed Roux-en-Y and not loop GJ. The average biliopancreatic
      limb length was 48 cm, and the average Roux limb was 114 cm. About one half of
      the surgeons (46%) measured the limb length with an open grasper, and few (7%)
      used a suture or umbilical tape. The antecolic and antegastric approaches were
      the more common. The percentage of those using the circular stapler, linear
      stapler, and hand sewing was 43%, 41%, and 21% for the GJ technique. Most
      surgeons (93%) routinely tested the GJ intraoperatively. The percentage of those
      using staple anastomosis and hand-sewn common enterotomy, double stapling, triple
      stapling, and hand sewing was 53%, 36%, 13%, and 1% for the jejunojejunostomy
      technique. Most surgeons (94%) closed at least one mesenteric defect. Also, most
      surgeons (95%) did not place a band around the pouch. CONCLUSION: Technical
      variations exist in how laparoscopic gastric bypass procedures are performed by
      American Society for Bariatric Surgery practicing surgeons. Additional research
      is needed to explore the links between the technical variations and outcomes.

PMID- 18069072
TI  - Italian multicenter experience of Roux-en-Y gastric bypass on vertical banded
      gastroplasty: four-year results of effective and safe innovative procedure
      enabling traditional endoscopic and radiographic study of bypassed stomach and
      biliary tract.
AB  - BACKGROUND: Cancer, perforation, and bleeding in the bypassed stomach after Roux
      en-Y gastric bypass (RYGB) are rare, but serious, complications that need an
      early diagnosis. Our goal was to perform gastric bypass such that traditional
      endoscopic and radiographic study of the gastric remnant would be possible and,
      at the same time, obtain results in terms of weight loss equivalent to those
      found after standard RYGB. A previously published study demonstrated that
      complete occlusion of the gastrogastric outlet was not necessary to lose weight.
      We have developed an open RYGB-on-vertical banded gastroplasty procedure.
      METHODS: Since 2002, 289 patients with a mean age of 40.1 +/- 14.8 years, mean
      body mass index of 51.4 +/- 7.3 kg/m(2), and mean percentage of excess body
      weight of 107.3% +/- 36.7% underwent RYGB-on-vertical banded gastroplasty as
      their primary procedure. RESULTS: The follow-up examinations included
      radiographic and, if necessary, endoscopic studies at 6 and 12 months
      postoperatively and annually thereafter. Two cases of anastomotic ulcer were
      detected, one of which involved band erosion. The percentage of excess weight
      loss was 48.2% +/- 18.8% after 6 months and 59.0% +/-17.7%, 63.3% +/- 13.9%,
      66.9% +/- 17.5%, and 70.0% +/- 17.7% after 1, 2, 3, and 4 years, respectively.
      The weight loss curve was similar to that for standard RYGB. CONCLUSION: The
      results of our study have shown that RYGB-on-vertical banded gastroplasty is as
      effective as traditional RYGB, while allowing for traditional radiography of the
      bypassed stomach in every patient. Endoscopy of the distal stomach and,
      therefore, the biliary tract, was also possible. These are the fundamental
      aspects of the procedure.

PMID- 18069073
TI  - Endoscopic sclerotherapy for dilated gastrojejunostomy of failed gastric bypass.
AB  - BACKGROUND: Gastric bypass is an effective treatment for morbid obesity and can
      result in >60% excess weight loss initially. It has been reported that a 10-15%
      weight regain can occur in these patients. Few options are available to prevent
      this weight regain. The injection of morrhuate sodium as sclerotherapy has been
      suggested to decrease the diameter of the gastrojejunostomy anastamosis. METHODS:
      A total of 71 patients underwent sclerotherapy at their gastrojejunostomy from
      July 2004 to August 2006. A retrospective review was performed of this group,
      including chart review, follow-up data with weight checks, and telephone
      interview findings. RESULTS: The average age of the patients was 45 years, and
      all but 4 patients were women. Sclerotherapy was done an average of 2.9 years
      after gastric bypass. The starting weight at endoscopy was an average of 218 lb
      18 lb heavier than the average nadir weight. The average diameter of the
      gastrojejunostomy was 2.3 cm. An average of 13 mL morrhuate sodium was injected
      circumferentially. Repeat therapy was performed in 35 patients (49%). No hospital
      admissions or complications occurred in relation to the procedure. During the 12
      month follow-up period, 72% of patients maintained or lost weight. The analysis
      showed a high body mass index (at endoscopy) to be the only predictive factor for
      successful weight maintenance or loss. CONCLUSION: These results suggest that the
      use of endoscopic sclerotherapy could stabilize weight gain after gastric bypass.
      A randomized controlled study is necessary to validate these findings.

PMID- 18069075
TI  - Cost-effectiveness analysis of laparoscopic gastric bypass, adjustable gastric
      banding, and nonoperative weight loss interventions.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) and laparoscopic Roux
      en-Y gastric bypass (LRYGB) are the two most commonly performed bariatric
      procedures. Although both procedures likely reduce healthcare expenditures
      related to the resolution of co-morbid conditions, they have different rates of
      perioperative risks and different rates of associated weight loss. We designed a
      model to evaluate the incremental cost-effectiveness of these procedures compared
      with nonoperative weight loss interventions and with each other. METHODS: We used
      a deterministic, payer-perspective model comparing the lifetime expected costs
      and outcomes of LAGB, LRYGB, and nonoperative treatment. The major endpoints were
      survival, health-related quality of life, and weight loss. Life expectancy and
      lifetime medical costs were calculated across age, gender, and body mass index
      (BMI) strata using previously published data. RESULTS: For both men and women,
      LRYGB and LAGB were cost-effective at <$25,000/quality-adjusted life-year (QALY)
      even when evaluating the full range of baseline BMI and estimates of adverse
      outcomes, weight loss, and costs. For base-case scenarios in men (age 35 y, BMI
      40 kg/m(2)), the incremental cost-effectiveness was $11,604/QALY for LAGB
      compared with $18,543/QALY for LRYGB. For base-case scenarios in women (age 35 y,
      BMI 40 kg/m(2)), the incremental cost-effectiveness was $8878/QALY for LAGB
      compared with $14,680/QALY for LRYGB. CONCLUSION: The modeled cost-effectiveness
      analysis showed that both operative interventions for morbid obesity, LAGB and
      RYGB, were cost-effective at <$25,000 and that LAGB was more cost-effective than
      RYGB for all base-case scenarios.

PMID- 18069076
TI  - Respiratory plasticity after perinatal hyperoxia is not prevented by antioxidant
      supplementation.
AB  - Perinatal hyperoxia attenuates the hypoxic ventilatory response in rats by
      altering development of the carotid body and its chemoafferent neurons. In this
      study, we tested the hypothesis that hyperoxia elicits this plasticity through
      the increased production of reactive oxygen species (ROS). Rats were born and
      raised in 60% O(2) for the first two postnatal weeks while treated with one of
      two antioxidants: vitamin E (via milk from mothers whose diet was enriched with
      1000 IU vitamin E kg(-1)) or a superoxide dismutase mimetic, manganese(III)
      tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP; via daily
      intraperitoneal injection of 5-10 mg kg(-1)); rats were subsequently raised in
      room air until studied as adults. Peripheral chemoreflexes, assessed by carotid
      sinus nerve responses to cyanide, asphyxia, anoxia and isocapnic hypoxia (vitamin
      E experiments) or by hypoxic ventilatory responses (MnTMPyP experiments), were
      reduced after perinatal hyperoxia compared to those of normoxia-reared controls
      (all P<0.01); antioxidant treatment had no effect on these responses. Similarly,
      the carotid bodies of hyperoxia-reared rats were only one-third the volume of
      carotid bodies from normoxia-reared controls (P <0.001), regardless of
      antioxidant treatment. Protein carbonyl concentrations in the blood plasma,
      measured as an indicator of oxidative stress, were not increased in neonatal rats
      (2 and 8 days of age) exposed to 60% O(2) from birth. Collectively, these data do
      not support the hypothesis that perinatal hyperoxia impairs peripheral
      chemoreceptor development through ROS-mediated oxygen toxicity.

PMID- 18069077
TI  - Determination of tegaserod by LC-ESI-MS/MS and its application to a
      pharmacokinetic study in healthy Chinese volunteers.
AB  - A simple, rapid and sensitive high performance liquid chromatography-electrospray
      ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) assay for determination of
      tegaserod in human plasma using diazepam as internal standard (IS) was
      established. After adjustment to a basic pH with sodium hydroxide, plasma was
      extracted by ethyl acetate and separated by high performance liquid
      chromatography (HPLC) on a reversed-phase C18 column with a mobile phase of
      methanol: 5 mM ammonium acetate (75:25, v/v, adjusting the pH to 3.5 with glacial
      acetic acid). The quantification of target compounds was obtained by using
      multiple reaction monitoring (MRM) transitions; m/z 302.5, 173.2 and 285.4, 193.2
      were measured in positive mode for tegaserod and internal standard (diazepam),
      respectively. The lower limit of quantification (LLOQ) was 0.05 ng/ml. The
      calibration curves were linear over the range 0.05-8.0 ng/ml (r=0.9996) for
      tegaserod. The mean absolute recovery of tegaserod was more than 85.56%. Intra-
      and inter-day variability values were less than 9.21% and 10.02%, respectively.
      The samples were stable for 8h under room temperature (25 degrees C, three freeze
      thaw cycles in 30 days and for 30 days under -70 degrees C). After administration
      of a single dose of tegaserod maleate 4 mg, 6 mg and 12 mg, respectively, the
      area under the plasma concentration versus time curve from time 0 h to 12 h (AUC0
      12) were (2.89+/-0.88), (5.32+/-1.21) and (9.38+/-3.42) ng h/ml, respectively;
      peak plasma concentration (Cmax) were (1.25+/-0.53), (2.21+/-0.52) and (4.34+/
      1.66) ng/ml, respectively; apparent volume of distribution (Vd/F) were (6630.5+/
      2057.8), (7615.2+/-2242.8) and (7163.7+/-2057.2) l, respectively; clearance rate
      (CL/F) were (1851.4+/-496.9), (1596.2+/-378.5) and (1894.2+/-459.3) l/h,
      respectively; time to Cmax (Tmax) were (1.00+/-0.21), (1.05+/-0.28) and (1.04+/
      0.16) h, respectively; and elimination half-life (t1/2) were (3.11+/-0.78),
      (3.93+/-0.92) and (3.47+/-0.53) h, respectively; MRT were (3.74+/-0.85), (4.04+/
      0.56) and (3.28+/-0.66) h, respectively. The essential pharmacokinetic parameters
      after oral multiple doses (6mg, b.i.d) were as follows: Cssmax, (2.72+/-0.61)
      ng/ml; Tmax, (1.10+/-0.25) h; Cssmin, (0.085+/-0.01) ng/ml; Cav, (0.54+/-0.12)
      ng/ml; DF, (4.84+/-0.86); AUCss, (6.53+/-1.5) ngh/ml. This developed and
      validated assay method had been successfully applied to a pharmacokinetic study
      after oral administration of tegaserod maleate in healthy Chinese volunteers at a
      single dose of 4 mg, 6 mg and 12 mg, respectively. The pharmacokinetic parameters
      can provide some information for clinical medication.

PMID- 18069078
TI  - Simultaneous determination of 33 amino acids and dipeptides in spent cell culture
      media by gas chromatography-flame ionization detection following liquid and solid
      phase extraction.
AB  - A rapid, sensitive and reproducible gas chromatographic method with flame
      ionization detection is described for the simultaneous identification and
      quantification of 33 amino acids and dipeptides in spent cell culture media in
      under seven minutes. The method involves the use of the EZ:faast(Phenomenex)
      amino acid sample testing kit. Instrumental and assay precision, percent
      recovery, linear range, limit of detection and peak identity in highly complex
      cell culture media containing either soy hydrolysate or fetal bovine serum were
      validated using gas chromatography-flame ionization detector (GC-FID).

PMID- 18069079
TI  - Applications of supercritical CO2 in the fabrication of polymer systems for drug
      delivery and tissue engineering.
AB  - Supercritical CO(2) has the potential to be an excellent environment within which
      controlled release polymers and dry composites may be formed. The low temperature
      and dry conditions within the fluid offer obvious advantages in the processing of
      water, solvent or heat labile molecules. The low viscosity and high diffusivity
      of scCO(2) offer the possibility of novel processing routes for polymer drug
      composites, but there are still technical challenges to overcome. Moreover, the
      low solubility of most drug molecules in scCO(2) presents both challenges and
      advantages. This review explores the current methods that use high pressure and
      scCO(2) for the production of drug delivery systems and the more specialized
      application of the fluid in the formation of highly porous tissue engineering
      scaffolds.

PMID- 18069080
TI  - Sensory shelf life estimation of minimally processed lettuce considering two
      stages of consumers' decision-making process.
AB  - The aim of the present work was to study the influence of context, particularly
      the stage of the decision-making process (purchase vs consumption stage), on
      sensory shelf life of minimally processed lettuce. Leaves of butterhead lettuce
      were placed in common polypropylene bags and stored at 5, 10 and 15 degrees C.
      Periodically, a panel of six assessors evaluated the appearance of the samples,
      and a panel of 40 consumers evaluated their appearance and answered "yes" or "no"
      to the questions: "Imagine you are in a supermarket, you want to buy a minimally
      processed lettuce, and you find a package of lettuce with leaves like this, would
      you normally buy it?" and "Imagine you have this leaf of lettuce stored in your
      refrigerator, would you normally consume it?". Survival analysis was used to
      calculate the shelf lives of minimally processed lettuce, considering both
      decision-making stages. Shelf lives estimated considering rejection to purchase
      were significantly lower than those estimated considering rejection to consume.
      Therefore, in order to be conservative and assure the products' quality, shelf
      life should be estimated considering consumers' rejection to purchase instead of
      rejection to consume, as traditionally has been done. On the other hand, results
      from logistic regressions of consumers' rejection percentage as a function of the
      evaluated appearance attributes suggested that consumers considered them
      differently while deciding whether to purchase or to consume minimally processed
      lettuce.

PMID- 18069081
TI  - Impulsivity is associated with the disinhibition but not restraint factor from
      the Three Factor Eating Questionnaire.
AB  - Recent data implicate impulsivity as a personality trait associated with obesity,
      binge eating and restrained eating. However, impulsivity is recognised as having
      multiple dimensions, and it remains unclear which aspects of impulsive behaviour
      best predict disordered eating. To try and elucidate further the relationship
      between impulsivity and eating behaviour, 147 women completed a behavioural
      measure and two self-report measures of impulsivity along with the Three Factor
      Eating Questionnaire (TFEQ). Overall scores on the Barratt Impulsiveness Scale
      (BIS-II), along with scores on the Non-planning and Motor Subscales of the BIS
      II, were higher in women scoring high on the TFEQ disinhibition (TFEQ-D) scale.
      Likewise, women scoring high on the TFEQ-D showed more impulsive choice when
      discounting hypothetical monetary awards. However, responses to measures of
      functional relative to dysfunctional impulsivity did not differ depending on TFEQ
      D score. No measure of impulsivity was related to scores on the TFEQ restraint
      scale. These data suggest that a tendency to act impulsively is associated with a
      tendency to overeat, and may be a factor which predicts the likelihood of the
      development of binge eating and the breakdown of dieting.

PMID- 18069082
TI  - Nasal carriage of meticillin-resistant Staphylococcus aureus in medical students.

PMID- 18069083
TI  - Intensive care unit environmental cleaning: an evaluation in sixteen hospitals
      using a novel assessment tool.
AB  - Despite isolation precautions and enhanced hand hygiene product use, the
      transmission of healthcare-associated pathogens remains a major problem. Recent
      studies have confirmed that microbial contamination of the environment in
      intensive care units (ICUs) can lead to colonisation and infection of patients.
      Although environmental disinfectants have been used to minimise the spread of
      microbial pathogens, suboptimal cleaning may limit the effectiveness of such
      activities. In order to evaluate the thoroughness of cleaning near-patient
      surfaces, a transparent, easily cleanable and environmentally stable solution was
      developed that fluoresces when exposed to UV light. The solution was used to mark
      a standardised group of frequently touched objects in ICU patient rooms following
      discharge cleaning. These sites were then evaluated after at least two patients
      had occupied the room and at least two terminal cleanings had been completed.
      Evaluation of 2320 objects in 197 patient areas disclosed that 57.1% of the
      standardised sites were cleaned following discharge of the room's occupant in the
      16 ICUs studied. Although high rates of cleaning (>80%) were found for toilet
      seats, sinks and tray tables, consistently low rates of cleaning (<30%) were
      documented for several objects at high risk of becoming contaminated with
      nosocomial pathogens, including bedpan cleaners, toilet area handholds, doorknobs
      and light switches.

PMID- 18069085
TI  - Tuberculocidal activity of a peroxymonosulphate-based disinfectant-detergent
      (Virkon).

PMID- 18069084
TI  - Virulence factors produced by strains of Staphylococcus aureus isolated from
      urinary tract infections.
AB  - Staphylococcus aureus infections are widely prevalent in West Africa and are
      often associated with urinary tract infections (UTIs). Virulence factors from S.
      aureus have rarely been described for such infections. The purpose of the current
      study was to determine the prevalence of toxins and adhesion factors obtained
      from S. aureus isolated from presumed primary UTIs at the Cotonou University
      Hospital (CUH) in Benin as compared with the Strasbourg University Hospital (SUH)
      in France. Both ambulatory and hospitalised patients were included in the study.
      Sixty-five independent strains of S. aureus from CUH and 35 strains from SUH were
      obtained over a four-month period. Virulence factors were characterised by
      immunodetection or multiplex polymerase chain reaction, and meticillin
      susceptibility was recorded. Approximately 50% of all isolates produced at least
      one enterotoxin. No isolate from SUH produced Panton-Valentine leucocidin (PVL),
      whereas 21.5% of the S. aureus isolates from CUH produced PVL (P<0.01). Six of 14
      (43%) PVL-positive isolates were meticillin-resistant. At SUH, the incidence of
      MRSA (57%) was significantly higher (P<0.01) than at CUH (14%). Genes encoding
      clumping factor B, and elastin and laminin binding proteins were detected in
      almost all isolates (80%), irrespective of the geographical origin. The results
      for elastin binding protein differed significantly from published data regarding
      isolates from other clinical origins. Staphylococcal toxins and adhesion factors
      may be important in the physiopathology of UTI.

PMID- 18069086
TI  - The antimicrobial activity of copper and copper alloys against nosocomial
      pathogens and Mycobacterium tuberculosis isolated from healthcare facilities in
      the Western Cape: an in-vitro study.
AB  - Clinical isolates of meticillin-resistant Staphylococcus aureus (MRSA),
      Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Candida
      albicans and Mycobacterium tuberculosis (MTB) were tested against copper (Cu) and
      its alloys. Stainless steel and polyvinylchloride (PVC) were used as controls.
      The amount of Cu required to inhibit test isolates at room temperature (24
      degrees C) and at 4 degrees C was determined. At room temperature, Cu, DZR Brass
      (Cu 62%, Pb 2.5%, arsenate 0.13% and Zn 22.5%) and Brass 70/30 (Cu 70% and zinc
      30%) inhibited C. albicans and K. pneumoniae at 60 min; nickel silver (NiAg)
      inhibited C. albicans at 60 min and K. pneumoniae at 270 min. P. aeruginosa was
      inhibited by Brass 70/30 and nickel silver (NiAg) at 180 min and at 270 min by Cu
      and DZR. Cu and DZR inhibited A. baumannii at 180 min while the other alloys were
      effective at 360 min. Stainless steel and PVC showed little or no inhibitory
      activity. Two M. tuberculosis strains, one isoniazid resistant (R267) and the
      other multidrug resistant (R432), demonstrated growth inhibition with Cu of 98%
      and 88% respectively compared with PVC; the other alloys were less active. Time
      to positivity (TTP) for R267 was >15 days with Cu and 11 days for the other
      alloys; with R432 it was 5 days. Effective inhibition of nosocomial pathogens and
      MTB by Cu and alloys was best when the Cu content was >55%.

PMID- 18069087
TI  - The effectiveness of disaster training for health care workers: a systematic
      review.
AB  - STUDY OBJECTIVE: Evidence-based medical literature is lacking about the best
      methods to train health care providers in disaster response. We systematically
      review the recent literature to report whether training interventions in disaster
      preparedness improve knowledge and skills in disaster response. METHODS: We
      searched MEDLINE through PubMed, ISI Web of Science, BIOSIS, Cumulative Index to
      Nursing and Allied Health (CINAHL), the Cochrane Library, ClinicalTrials.gov, the
      Public Affairs Information Service, and Education Full Text. Selected journals,
      articles, and other comprehensive reports were also reviewed for relevant
      citations. Subjects of eligible articles were hospital-based and out-of-hospital
      health care providers. Articles meeting inclusion criteria were published in
      English between January 2000 and December 2005, described a training exercise
      undertaken to further knowledge or skills in disaster response, measured a
      quantitative and objective outcome, and used a control group. Included studies
      were independently reviewed by 2 researchers, and study quality was assessed with
      criteria adapted from the US Preventive Services Task Force and the Centre for
      Reviews and Dissemination. RESULTS: We identified 258 studies. Nine studies are
      included in this review. Computer- and lecture-based training interventions may
      be effective in increasing disaster-related knowledge for out-of-hospital
      providers, though questions about study design and quality may cast doubt on the
      results. Evidence about effectiveness of training for inhospital providers is
      inconclusive. Comparison across studies is difficult because of diversity in
      study subjects, designs, and interventions. Results are likely biased by
      contamination from outside events. CONCLUSION: The available evidence is
      insufficient to determine whether training interventions for health care
      providers are effective in improving knowledge and skills in disaster response.

PMID- 18069088
TI  - Increasing rates of emergency department visits for elderly patients in the
      United States, 1993 to 2003.
AB  - STUDY OBJECTIVE: In 2005, the Centers for Disease Control and Prevention reported
      increasing emergency department (ED) visit rates per 100 people. The greatest
      increase in visit rate was among individuals 65 years and older. Given that older
      ED visitors have longer lengths of stay in the ED, are more likely to be
      admitted, and compose a growing proportion of the American population, this
      finding could have a significant negative effect on ED crowding. The first step
      toward addressing this issue is a better understanding of the nature of these
      visits. METHODS: We performed trend analysis for persons aged 65 years and older
      using 1993 to 2003 National Hospital Ambulatory Medical Care Survey data, an
      annual national sample of visits to the EDs of nonfederal general and short-stay
      hospitals. SAS 9.1 computed population estimates and standard errors for number
      of ED visits. Annual census data were used to compute visit rates per 100
      persons. A least-squares test for trend determined slopes and 95% confidence
      intervals. RESULTS: Visits for patients aged 65 to 74 years increased 34% during
      the study period. The visit rate for blacks increased 93% to 77 visits per 100
      population, whereas the rate for whites increased 26% to 36 visits per 100. The
      admission rate did not change significantly during the study period. The number
      of visits at which 3 or more medications were prescribed increased 44%. The
      increased visits occurred primarily in the category of "other and undefined"
      diagnoses (90% increase). CONCLUSION: If these trends continue, ED visits in the
      United States for the 65- to 74-year-old group could nearly double from 6.4
      million visits to 11.7 million visits by 2013.

PMID- 18069089
TI  - Anxiolytic- and antidepressant-like activities of H-Dmt-Tic-NH-CH(CH2-COOH)-Bid
      (UFP-512), a novel selective delta opioid receptor agonist.
AB  - Knockout and pharmacological studies have shown that delta opioid peptide (DOP)
      receptor signalling regulates emotional responses. In the present study, the in
      vitro and in vivo pharmacological profile of the DOP ligand, H-Dmt-Tic-NH-CH(CH2
      COOH)-Bid (UFP-512) was investigated. In receptor binding experiments performed
      on membranes of CHO cells expressing the human recombinant opioid receptors, UFP
      512 displayed very high affinity (pKi 10.20) and selectivity (>150-fold) for DOP
      sites. In functional studies ([35S]GTP gamma S binding in CHOhDOP membranes and
      electrically stimulated mouse vas deferens) UFP-512 behaved as a DOP selective
      full agonist showing potency values more than 100-fold higher than DPDPE. In
      vivo, in the mouse forced swimming test, UFP-512 reduced immobility time both
      after intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration.
      Similar effects were recorded in rats. Moreover, UFP-512 evoked anxiolytic-like
      effects in the mouse elevated plus maze and light-dark aversion assays. All these
      in vivo actions of UFP-512 were fully prevented by the selective DOP antagonist
      naltrindole (3 mg/kg, s.c.). In conclusion, the present findings demonstrate that
      UFP-512 behaves as a highly potent and selective agonist at DOP receptors and
      corroborate the proposal that the selective activation of DOP receptors elicits
      robust anxiolytic- and antidepressant-like effects in rodents.

PMID- 18069090
TI  - Differential pharmacological properties of GABAA/benzodiazepine receptor complex
      in dorsal compared to ventral rat hippocampus.
AB  - Several studies have indicated a functional differentiation across the
      septotemporal axis of rat hippocampus. Our previous results have shown that the
      alpha 1 beta 2 gamma 2-GABAA receptor subtype dominates in dorsal hippocampus
      (DH), while the alpha 2 beta 1 gamma 2-subtype prevails in ventral hippocampus
      (VH). We therefore studied possible differences in the pharmacological properties
      and receptor binding parameters of the GABAA receptor subtypes between DH and VH,
      by examining: (1)(a) the specific binding of [3H]-flunitrazepam (Benzodiazepine
      sites agonist) by using quantitative autoradiography, (b) the kinetic parameters
      of [3H]-flunitrazepam specific binding, by using the "wipe off" technique and (2)
      the competitive displacement of [3H]-flunitrazepam binding by using zolpidem
      (selective agonist of the alpha 1-subtype) and L-655,708 (selective inverse
      agonist of the alpha 5-subtype) and the enhancement of [3H]-flunitrazepam binding
      by using etomidate (selective positive modulator of the beta 2-subunit), in an
      autoradiographical saturation kinetic study. Our results showed in VH compared to
      DH: (A) lower level of [3H]-flunitrazepam binding, apparently due to weaker
      binding affinity (higher KD value), since no differences in the Bmax value could
      be detected, (B) higher IC50 values for zolpidem and lower IC50 values for L
      655,708 and (C) higher EC50 values for etomidate. In conclusion, the lower
      binding for zolpidem and etomidate and the higher binding for L-655,708 observed
      in VH support the evidence that the alpha 1 beta 2 gamma 2-GABAA receptor subtype
      dominates in DH and the alpha 5-subtype prevails in VH. Further, our results
      suggest differential pharmacological effects of the benzodiazepines in DH
      compared to VH, with the sedative effects being more potent in the dorsal
      hippocampus.

PMID- 18069091
TI  - Comparison of the time courses of selective gene expression and dopaminergic
      depletion induced by MPP+ in MN9D cells.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease characterized by
      progressive loss of midbrain dopaminergic neurons with unknown etiology. MPP+ (1
      methyl-4-phenylpyridinium ion) is the active metabolite of the neurotoxin 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces Parkinson's-like
      symptoms in humans and animals. MPTP/MPP+ produces selective dopaminergic
      neuronal degeneration, therefore, these agents are commonly used to study the
      pathogenesis of PD. However, the mechanisms of their toxicity have not been fully
      elucidated. Recently, we reported in a microarray study using a midbrain-derived
      dopaminergic neuronal cell line, MN9D, that MPP+ induced significant changes in a
      number of genes known to be associated with the dopaminergic system. In this
      study, we investigated the expression time courses of six genes using real-time
      RT-PCR, and compared them with the progressive dopaminergic depletion caused by
      MPP+. Our data showed that dopamine content was significantly decreased after
      0.5h of MPP+ (200 microM) exposure and was completely depleted after 40 h. The
      expression of Gpr37, which is closely related to the pathogenesis of autosomal
      recessive juvenile Parkinsonism, was up-regulated after 0.5h, and stayed up
      regulated up to 48 h. Txnip, which is critical to the adjustment of cellular
      redox status, was down-regulated after 1h and stayed down-regulated up to 48 h.
      Ldh1 and Cdo1, which are also involved in oxidative stress, were down-regulated
      after 16 h and stayed down-regulated up to 48 h. Two pro-apoptotic genes, Egln3
      and Bnip3, were down-regulated after 2 and 4h, and stayed down-regulated up to 48
      h. These findings suggested that the time course of expression for multiple genes
      correlated with the dopaminergic depletion; and MPP+-induced neurotoxicity in
      MN9D cells could be used as a model to further explore the roles of these and
      other genes in the pathogenesis and possible treatment of PD.

PMID- 18069093
TI  - Regiospecific microwave-assisted synthesis and cytotoxic activity against human
      breast cancer cells of (RS)-6-substituted-7- or 9-(2,3-dihydro-5H-1,4
      benzodioxepin-3-yl)-7H- or -9H-purines.
AB  - Extended studies on the synthesis and pharmacological evaluation of (RS)-6
      substituted-7 or 9-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-7H- or -9H-purines are
      presented. The microwave-assisted organic synthesis has provided faster access to
      the target compounds with the advantage of selective obtaining the N-7' or N-9'
      regioisomers simplifying their isolation. To test the behaviour of the products
      (including the purine bases) on cellular systems, cytotoxic activity against the
      MCF-7 human breast cancer cell line was determined, and the three most active
      compounds were used to study the cell cycle distribution and apoptosis in the MCF
      7 cell line.

PMID- 18069092
TI  - TNFR-associated factor-2 (TRAF-2) in Alzheimer's disease.
AB  - Levels of tumor necrosis factor-alpha (TNF-alpha) are increased in the brain in
      Alzheimer's disease (AD). The TNF-alpha/TNF-R signaling pathways involve complex
      interactions between several proteins, including TNF-receptor-associated factor-2
      (TRAF-2). We have examined the distribution and levels of TRAF-2 in AD and
      control brains and also whether single nucleotide polymorphisms (SNPs) in the
      TRAF-2 gene are associated with AD and influence TRAF-2 expression.
      Immunohistochemistry demonstrated TRAF-2 in AD and control cortex in neurons,
      within plaque-associated neurites and some neurofibrillary tangles. Western blots
      revealed a band of the expected apparent molecular mass (approximately 50kDa) for
      TRAF-2, in homogenates of AD and control cortex. RT-PCR showed the levels of TRAF
      2 mRNA to be significantly higher in the frontal cortex of AD than control brains
      (p=0.015). TRAF-2 mRNA expression was not linked to any SNPs. The 3' UTR SNP
      (rs7852970) GG allele was significantly protective against AD (p=0.030). Our
      findings suggest that the TRAF-2 pathway is involved AD. The mechanisms are
      currently unclear and need further examination.

PMID- 18069094
TI  - Substituted benzylaminoalkylindoles with preference for the sigma2 binding site.
AB  - In the attempt to develop new sigma ligands we synthesized a series of N-benzyl-3
      [1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylpropan-1-amines and N-benzyl-4-[1-(4
      fluorophenyl)-1H-indol-3-yl]-N-methylbutan-1-amines variously substituted on the
      phenyl ring. The displacement percentages of [3H]-DTG and [3H]-(+)-pentazocine
      determined in rat liver homogenates by these compounds at the fixed 100 nM
      concentration have been determined as a preliminary evaluation of their sigma1
      and sigma2 affinity, respectively. The results suggested that the phenyl
      substituents may positively modulate, in comparison with the unsubstituted
      compound, the ability to displace [3H]-DTG from sigma2 sites, whereas the same
      phenyl substituents reduced the displacement percentages of [3H]-(+)-pentazocine
      from sigma1 sites. Some of these compounds were selected for radioligand binding
      assays. Compounds with a butylene intermediate chain displayed the greatest
      binding affinity for sigma2 over sigma1 receptors. The butylene derivative with
      2,4-dimethyl substitution on the phenyl ring showed the greatest sigma2 affinity
      (sigma2Ki=5.9 nM) and an appreciable sigma2 over sigma1 selectivity
      (sigma1Ki/sigma2Ki=22). The obtained results suggest that a butylene chain
      separating the indole moiety from variously substituted benzylamino groups may be
      required to their interaction with a hypothetical secondary sigma2 binding site.

PMID- 18069095
TI  - Vaccination with in vitro grown whole tumor cells induces strong immune responses
      and retards tumor growth in a murine model of colorectal liver metastases.
AB  - In vitro adaptation of a murine colorectal cell line (MoCR) rendered it less
      aggressive and more immunogenic than the in vivo passaged parent tumor.
      Vaccination of syngeneic mice with the in vitro cultured tumor cells was shown to
      induce immune responses and protection against tumor challenge, thus overcoming
      the need for antigen selection and adjuvants. A syngeneic murine model of
      colorectal cancer (CRC) liver metastasis was used. In a prophylactic setting mice
      vaccinated with in vitro cultured tumor cells produced strong cellular immune
      responses and significant inhibition of tumor growth, compared to sham vaccinated
      controls. In a therapeutic setting however, vaccination exacerbated tumor growth,
      suggesting that the presence of tumor subverts the course of the immune response.
      The mechanisms of this subversion need to be investigated and counteracted for
      successful immunotherapy.

PMID- 18069096
TI  - Immunization with West Nile virus envelope domain III protects mice against
      lethal infection with homologous and heterologous virus.
AB  - The Japanese encephalitis virus (JEV) serocomplex-group consists of mosquito
      borne flaviviruses, which include West Nile virus (WNV) and JEV, and both may
      cause severe encephalitis in humans. WNV has spread rapidly across the United
      States since its introduction in 1999 and its geographical distribution within
      the western hemisphere is expected to further expand, whereas, JEV is the most
      common cause of viral encephalitis in Southeast Asia, China and India. Currently,
      there is no registered human vaccine or specific therapy to prevent or treat WNV
      infection. Here we describe the efficacy of recombinant domain III (DIII) of WNV
      glycoprotein E in a mouse model. It induces high neutralizing antibody titers, as
      well as, protection against lethal WNV infection in C57BL/6 mice. This vaccine
      preparation also afforded partial protection against lethal JEV infection.

PMID- 18069097
TI  - Safety of the RTS,S/AS02A malaria vaccine in Mozambican children during a Phase
      IIb trial.
AB  - RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on the Plasmodium
      falciparum circumsporozoite surface antigen and is currently the most advanced
      malaria vaccine candidate in development. A proof of concept phase IIb trial of
      the RTS,S/AS02A in Mozambican children aged 1-4 years determined a vaccine
      efficacy against risk of clinical malaria of 35.3% (95% CI 21.6-46.6; p<0.0001)
      and against severe malaria of 48.6% (95% CI 12.3-71.0; p=0.02). We evaluated the
      safety of the RTS,S/AS02A vaccine. 2022 children that received at least one
      vaccine dose of RTS,S/AS02A or control vaccines were included in the intention to
      treat safety analysis. Vaccine safety was evaluated using active and passive
      follow-up. Participants were observed for at least 1h after each dose. Trained
      field workers visited children at home daily for the next 3 days to record
      solicited and unsolicited local and general symptoms. Investigators followed-up
      participants with severe adverse events until month 21. Overall, we recorded 1712
      unsolicited adverse events after vaccination, 53% in the intervention and 47% in
      the control group. Most unsolicited adverse events reported with RTS,S/AS02A were
      self-limited, and participants recovered without sequelae. Local reactogenicity
      increased with the number of doses. The proportion of children experiencing
      serious adverse events was lower in the RTS,S/AS02A recipients compared to the
      control group (Engerix-Btrade mark or Prevnartrade mark and Hiberixtrade mark).
      Overall, these results indicate that the RTS,S/AS02A vaccine has a good safety
      profile and well tolerated when given in three doses to semi-immune children
      living in malaria-endemic areas.

PMID- 18069098
TI  - Impact of arbuscular mycorrhizal fungi on uranium accumulation by plants.
AB  - Contamination by uranium (U) occurs principally at U mining and processing sites.
      Uranium can have tremendous environmental consequences, as it is highly toxic to
      a broad range of organisms and can be dispersed in both terrestrial and aquatic
      environments. Remediation strategies of U-contaminated soils have included
      physical and chemical procedures, which may be beneficial, but are costly and can
      lead to further environmental damage. Phytoremediation has been proposed as a
      promising alternative, which relies on the capacity of plants and their
      associated microorganisms to stabilize or extract contaminants from soils. In
      this paper, we review the role of a group of plant symbiotic fungi, i.e.
      arbuscular mycorrhizal fungi, which constitute an essential link between the soil
      and the roots. These fungi participate in U immobilization in soils and within
      plant roots and they can reduce root-to-shoot translocation of U. However, there
      is a need to evaluate these observations in terms of their importance for
      phytostabilization strategies.

PMID- 18069099
TI  - Gamma radiation doses to people living in Western Sweden.
AB  - Indoor environments contribute to gamma radiation in the general population. The
      aims of the present study were to investigate average gamma radiation doses in a
      rural and an urban area of Sweden, compare indoor dose rates with personal
      exposure, and study the effects of building characteristics on radiation levels.
      Radiation was measured with thermoluminescence dosimeters (TLDs). Repeated
      measurements were performed with TLDs worn by participants (n=46) and placed in
      their dwellings. Personal dose rates were 0.092microSv/h (rural) and
      0.096microSv/h (urban). The mean effective gamma dose rates in dwellings were
      0.091microSv/h (rural) and 0.11microSv/h (urban), which are higher than the world
      average. Dose rates in apartments were higher than in detached houses and higher
      for concrete than wooden dwellings. Personal dose rates were strongly associated
      with dwelling dose rates (r(p)=0.68, p<0.01) and could be modelled. Within
      participant variability was low.

PMID- 18069100
TI  - Arbuscular mycorrhiza reduces phytoextraction of uranium, thorium and other
      elements from phosphate rock.
AB  - Uptake of metals from uranium-rich phosphate rock was studied in Medicago
      truncatula plants grown in symbiosis with the arbuscular mycorrhizal fungus
      Glomus intraradices or in the absence of mycorrhizas. Shoot concentrations of
      uranium and thorium were lower in mycorrhizal than in non-mycorrhizal plants and
      root-to-shoot ratio of most metals was increased by mycorrhizas. This protective
      role of mycorrhizas was observed even at very high supplies of phosphate rock. In
      contrast, phosphorus uptake was similar at all levels of phosphate rock,
      suggesting that the P was unavailable to the plant-fungus uptake systems. The
      results support the role of arbuscular mycorrhiza as being an important component
      in phytostabilization of uranium. This is the first study to report on
      mycorrhizal effect and the uptake and root-to-shoot transfer of thorium from
      phosphate rock.

PMID- 18069101
TI  - Long-term outcomes for mothers who have or have not held their stillborn baby.
AB  - OBJECTIVES: to investigate long-term outcomes of mothers who have or have not
      held their stillborn baby, and predictors of having held the baby. DESIGN: postal
      questionnaires. SETTING: a nation-wide cohort study of mothers who gave birth to
      a singleton stillborn baby in Sweden in 1991. PARTICIPANTS: 314 out of 380 women
      answered the questionnaire and 309 reported whether or not they had held their
      baby. MEASUREMENTS: scales measuring anxiety, depression and well-being.
      FINDINGS: 126 (68%) mothers of 185 babies stillborn after 37 gestational weeks
      had held their baby and 82 (68%) mothers of 120 babies stillborn at gestational
      weeks 28-37 had also done so. Compared with mothers who agreed completely with
      the statement that staff gave enough support to hold the baby, mothers who did
      not agree were less likely to have held their baby [relative risk (RR) 4.1; 95%
      confidence interval (CI) 2.7-6.1], and mothers with a low level of education were
      less likely to have held their baby than mothers with a higher level of education
      (RR 2.2; 95% CI 1.3-3.8). Mothers who had not held their babies born after 37
      gestational weeks had an increased risk of headache (RR 4.3; 95% CI 1.1-16.5),
      and they were less satisfied with their sleep (RR 2.7; 95% CI 1.5-5.0). The
      increased risk of long-term outcomes associated with not holding, compared with
      holding, a stillborn baby were less pronounced for women who gave birth at
      gestational week 28-37 compared with women who gave birth after 37 gestational
      weeks. KEY CONCLUSIONS: in this cohort, we found an overall beneficial effect of
      having held a stillborn baby born after 37 gestational weeks, whereas findings
      for having held a stillborn baby born at gestational weeks 28-37 are uncertain.
      The attitude of staff influenced whether or not the mother held her stillborn
      baby. IMPLICATIONS FOR PRACTICE: if the mother is guided by staff in a sensitive
      way to hold her stillborn term baby, the experience will possibly be beneficial
      for her in the long term.

PMID- 18069102
TI  - Resolving inconsistencies in defining the target orientation for the acetabular
      cup angles in total hip arthroplasty.
AB  - BACKGROUND: Dislocation following total hip arthroplasty is a major complication
      and malorientation of the acetabular cup is one of the primary factors affecting
      dislocation. Different conventions used to describe the cup orientation produce
      significant variations in the recommendations for correct positioning, which in
      turn make it difficult for clinicians to properly interpret and apply previously
      reported studies. METHODS: We examined nine articles presenting recommendations
      for the range of target orientations of the acetabular cup to minimize the risk
      of dislocation (referred to as the 'safe zone'). Those studies included five ways
      to define the cup orientation and two methods to define the reference frame. We
      converted those recommendations to a single representation based on the
      radiographic angles expressed in the pelvic frame reference. FINDINGS: After
      conversion, the mean recommended anteversion angle was shifted downward by 5
      degrees (P<0.01). Also, the target orientation recommendations became more
      consistent, especially for the anteversion angles where the standard errors of
      the upper and lower limits were reduced by 61% (P=0.02) and 23% (P=0.04),
      respectively. INTERPRETATION: The choice of reference frame and the definition
      for acetabular cup orientation angles can have a significant effect on the target
      orientation for the acetabular cup. Recommendations for the target orientation
      should always explicitly state which reference frame and angle definition is
      being used. The averaged recommendation of the studies assessed here is 41
      degrees inclination and 16 degrees anteversion in radiographic angles or 39
      degrees inclination and 21 degrees anteversion in operative angles, both
      expressed in the pelvic reference frame.

PMID- 18069103
TI  - Avoidance test with Enchytraeus albidus (Enchytraeidae): effects of different
      exposure time and soil properties.
AB  - Enchytraeids are ecologically relevant soil species and are commonly used in
      standardized toxicity tests. Their rapid reaction to a chemical exposure can be
      used as a toxicological measurement endpoint that assesses the avoidance
      behavior. The objectives of this investigation were to determine the effects of
      soil properties on the avoidance behavior of Enchytraeus albidus and to optimize
      the duration of avoidance test. The avoidance tests included (1) exposures in
      OECD artificial soil with standard or modified properties (pH, clay or peat
      content), and (2) exposures to copper chloride, cadmium chloride, and to the
      organic pesticides dimethoate and phenmedipham for different time periods.
      Results showed that alteration of OECD soil constituents significantly affected
      the avoidance behavior of enchytraeids, and that the 48-h exposure was the
      optimal duration of the test. Consideration of soil properties is important for
      selecting appropriate experimental design and interpreting the results of the
      enchytraeid avoidance test.

PMID- 18069104
TI  - Seasonal variation of heavy metals in ambient air and precipitation at a single
      site in Washington, DC.
AB  - Atmospheric samples of precipitation and ambient air were collected at a single
      site in Washington, DC, for 7 months (for ambient air samples) and 1 year (for
      wet deposition samples) and analyzed for arsenic, cadmium, chromium and lead. The
      ranges of heavy metal concentrations for 6-day wet deposition samples collected
      over the 1-year period were 0.20-1.3 microg/l, 0.060-5.1 microg/l, 0.062-4.6
      microg/l and 0.11-3.2 microg/l for arsenic, cadmium, chromium and lead,
      respectively, with a precision better than 5% for more than 95% of the
      measurements. The ranges of heavy metal concentrations for the 6-day ambient air
      samples were 0.800-15.7 ng/m(3), 1.50-30.0 ng/m(3), 16.8-112 ng/m(3), and 2.90
      137 ng/m(3) for arsenic, cadmium, chromium and lead, respectively, with a
      precision better than 10%. The spread in the heavy metal concentration over the
      observation period suggests a high seasonal variability for heavy metal content
      in both ambient air and wet deposition samples.

PMID- 18069105
TI  - Predicting sublethal effects of herbicides on terrestrial non-crop plant species
      in the field from greenhouse data.
AB  - Guidelines provided by OECD and EPPO allow the use of data obtained in greenhouse
      experiments in the risk assessment for pesticides to non-target terrestrial
      plants in the field. The present study was undertaken to investigate the
      predictability of effects on field-grown plants using greenhouse data. In
      addition, the influence of plant development stage on plant sensitivity and
      herbicide efficacy, the influence of the surrounding vegetation on individual
      plant sensitivity and of sublethal herbicide doses on the biomass, recovery and
      reproduction of non-crop plants was studied. Results show that in the future, it
      might well be possible to translate results from greenhouse experiments to field
      situations, given sufficient experimental data. The results also suggest
      consequences at the population level. Even when only marginal effects on the
      biomass of non-target plants are expected, their seed production and thereby
      survival at the population level may be negatively affected.

PMID- 18069106
TI  - Sodium and chloride accumulation in leaf, woody, and root tissue of Populus after
      irrigation with landfill leachate.
AB  - The response of Populus to irrigation sources containing elevated levels of
      sodium (Na(+)) and chloride (Cl(-)) is poorly understood. We irrigated eight
      Populus clones with fertilized well water (control) (N, P, K) or municipal solid
      waste landfill leachate weekly during 2005 and 2006 in Rhinelander, Wisconsin,
      USA (45.6 degrees N, 89.4 degrees W). During August 2006, we tested for
      differences in total Na(+) and Cl(-) concentration in preplanting and harvest
      soils, and in leaf, woody (stems+branches), and root tissue. The leachate
      irrigated soils at harvest had the greatest Na(+) and Cl(-) levels. Genotypes
      exhibited elevated total tree Cl(-) concentration and increased biomass (clones
      NC14104, NM2, NM6), elevated Cl(-) and decreased biomass (NC14018, NC14106,
      DM115), or mid levels of Cl(-) and biomass (NC13460, DN5). Leachate tissue
      concentrations were 17 (Na(+)) and four (Cl(-)) times greater than water. Sodium
      and Cl(-) levels were greatest in roots and leaves, respectively.

PMID- 18069107
TI  - Sequential sorption of lead and cadmium in three tropical soils.
AB  - It is important to examine mechanisms of Pb and Cd sorption in soils to
      understand their bioavailability. The ability of three tropical soils to retain
      Pb, Cd, and Ca was evaluated. The objectives of this study were to (1) determine
      the extent to which soil sorption sites are metal specific, (2) investigate the
      nature of reactions between metals and soil surfaces, and (3) identify how metals
      compete for sorption sites when they are introduced to soils sequentially or
      concurrently. Lead was shown to be much less exchangeable than Cd and inhibited
      Cd sorption. Cadmium had little effect on Pb sorption, though both Ca and Cd
      inhibited the adsorption of Pb at exchange sites. Lead appears to more readily
      undergo inner-sphere surface complexation with soil surface functional groups
      than either Cd or Ca. Thus, regardless of when Pb is introduced to a soil, it
      should be less labile than Cd.

PMID- 18069108
TI  - The utility of the K6/ODC transgenic mouse as an alternative short term dermal
      model for carcinogenicity testing of pharmaceuticals.
AB  - The use of transgenic rodents may overcome many limitations of traditional cancer
      studies. Regulatory perspectives continue to evolve as new models are developed
      and validated. The transgenic mouse, K6/ODC, develops epidermal tumors when
      exposed to genotoxic carcinogens. In this study, K6/ODC mice were evaluated for
      model fitness and health robustness in a 36-week study to determine oncogenic
      risk of residual DNA in vaccines from neoplastic cell substrates. K6/ODC and
      C57BL/6 mice were treated with T24-H-ras expression plasmid, carrier vector DNA,
      or saline topically or by subcutaneous injection. One group of K6/ODC mice
      received 7,12-dimethylbenz-[a]anthracene [DMBA] dermally. Only DMBA-treated mice
      developed papillomas by six weeks, increasing in incidence to 25 weeks. By week
      11, many K6/ODC mice showed severe dehydration and dermal eczema. By week 32,
      (6/8) surviving K6/ODC mice showed loss of mobility and balance. Microscopic
      evaluation of tissues revealed dermal/sebaceous gland hyperplasia, follicular
      dystrophy, splenic atrophy, and amyloid deposition/neutrophilic infiltration
      within liver, heart, and spleen, in all K6/ODC mice. Pathology was not detected
      in C57BL/6 mice. Progressive adverse health, decreased survival, and failure to
      develop papillomas to the H-ras plasmid suggest that K6/ODC mice may be an
      inappropriate alternative model for detection of oncogenic DNA and pharmaceutical
      carcinogenicity testing.

PMID- 18069109
TI  - Overview of the mineralogy of the Biwabik Iron Formation, Mesabi Iron Range,
      northern Minnesota.
AB  - The mineralogy of the Biwabik Iron Formation changes dramatically from west to
      east as the formation nears the basal contact of the Duluth Complex. This
      reflects a contact metamorphism that took place with the emplacement of the
      igneous Duluth Complex at temperatures as high as 1200 degrees C. However, the
      mineralogy of the Biwabik Iron Formation also varies vertically through the
      stratigraphy of the unit. This variability in both the vertical and horizontal
      dimensions makes it difficult to predict exact horizons where specific minerals
      will occur. The iron-formation has been subdivided into four broad stratigraphic
      units (lower cherty, lower slaty, upper cherty, and upper slaty) and into four
      lateral mineralogical zones (1-4). Zone 1, the westernmost zone, is characterized
      by quartz, magnetite, hematite, carbonates, talc, chamosite, greenalite,
      minnesotaite, and stilpnomelane. The silicate mineralogy in Zone 2 of the Biwabik
      Iron Formation changes very little. However, the minerals begin to change
      dramatically in Zone 3. Most significantly, Zone 3 is characterized by the
      appearance of grunerite in both a tabular form and a fibrous form. In Zone 4, the
      original silicate minerals have completely reacted, and a new suite of minerals
      occupies the iron-formation. These include grunerite, hornblende, hedenbergite,
      ferrohypersthene (ferrosilite), and fayalite.

PMID- 18069110
TI  - Low-dose dietary chlorophyll inhibits multi-organ carcinogenesis in the rainbow
      trout.
AB  - We recently reported that chlorophyll (Chl) strongly inhibits aflatoxin B(1)
      preneoplasia biomarkers in rats when administered by co-gavage (Simonich et al.,
      2007. Natural chlorophyll inhibits aflatoxin B1-induced multi-organ
      carcinogenesis in the rat. Carcinogenesis 28, 1294-1302.). The present study
      extends this by examining the effects of dietary Chl on tumor development, using
      rainbow trout to explore ubiquity of mechanism. Duplicate groups of 140 trout
      were fed diet containing 224 ppm dibenzo[a,l]pyrene (DBP) alone, or with 1000
      6000 ppm Chl, for 4 weeks. DBP induced high tumor incidences in liver (51%) and
      stomach (56%), whereas Chl co-fed at 2000, 4000 or 6000 ppm reduced incidences in
      stomach (to 29%, 23% and 19%, resp., P<0.005) and liver (to 21%, 28% and 26%,
      resp., P<0.0005). Chlorophyllin (CHL) at 2000 ppm gave similar protection. Chl
      complexed with DBP in vitro (2Chl:DBP, K(d1)=4.44+/-0.46 microM, K(d2)=3.30+/
      0.18 microM), as did CHL (K(d1)=1.38+/-0.32 microM, K(d2)=1.17+/-0.05 microM),
      possibly explaining their ability to inhibit DBP uptake into the liver by 61-63%
      (P<0.001). This is the first demonstration that dietary Chl can reduce
      tumorigenesis in any whole animal model, and that it may do so by a simple,
      species-independent mechanism.

PMID- 18069111
TI  - The protective effects of ginsenosides on human erythrocytes against hemin
      induced hemolysis.
AB  - Panax ginseng has been used in traditional Chinese medicine to enhance stamina
      and capacity to deal with fatigue and physical stress. Many reports have been
      devoted to the effects of ginsenosides on many in vitro or in vivo experimental
      systems. The major aim of this work is to investigate the protective effects of
      12 individual ginsenosides including Rb1, Rb3, Rc, Rd, Re, Rg1, Rg2, Rg3, Rh1,
      Rh2, R1 and pseudoginsenoside F11, together with the central structures of
      aforementioned ginsenosides, 20(S)-protopanaxadiol (PD) and 20(S)
      protopanaxatriol (PT), on hemin-induced hemolysis of human erythrocytes. This is
      because hemin can induce hemolysis by accelerating the potassium leakage,
      dissociating skeletal proteins and prohibiting some enzymes in the membrane of
      erythrocyte. Thus, the structure-activity-relationship (SAR) between ginsenosides
      and protective effects has been screened in this in vitro experimental system. It
      is found that Rh2 and Rg3 intensify hemolysis in the presence of hemin, and
      initiate hemolysis even in the absence of hemin. All the other ginsenosides
      protect human erythrocytes against hemin-induced hemolysis more or less. The
      overall sequence is Rc>Rd>Re approximately Rb1>Rg1 approximately Rh1>Rb3
      approximately Rg2 approximately R1 approximately F11 approximately PT. In
      addition, the protective effects of PD and PT have been detected, and found that
      PD promotes hemolysis appreciably, whereas PT protects erythrocytes efficiently.
      Moreover, the protective effects of PT ginsenosides are similar to PT itself, and
      the protective effects of PD ginsenosides vary remarkably, demonstrating that the
      positions of the sugar moieties make the protective activities of ginsenosides
      complicated. Especially, sugar moiety at 20-position is critical for PD
      ginsenosides to inhibit hemolysis, whereas hydroxyl group at 3-position is
      important for PT ginsenosides. The present result may be useful for understanding
      the SAR of ginsenosides.

PMID- 18069113
TI  - The repeatability of human dentine permeability measurement in vitro.
AB  - OBJECTIVE: The aim of this study was to determine the repeatability of apparatus
      designed to assess dentine permeability at two different pressures. METHOD: Forty
      five human coronal tooth portions were prepared and permeability was measured at
      two separate time points, 5h apart, at 14 cm H2O pressure and then at 100 cm H2O
      pressure. Repeatability was determined using the limits of agreement (LOA)
      method. RESULTS: The results showed equal mean permeability of 0.6 microl at both
      time 1 and time 2 at 14 cm H2O pressure, and 2.7 and 2.5 microl at time 1 and
      time 2, respectively, at 100 cm H2O pressure. At 14 cm H2O pressure, the LOA were
      (-0.4, 0.4)microl and at 100 cm H2O pressure the LOA were (-0.2, 0.6)microl.
      CONCLUSION: Although repeatability measurement at 14 cm H2O pressure appeared to
      be acceptable, the higher permeability values at 100 cm H2O pressure may make the
      latter the pressure of choice despite the small bias.

PMID- 18069112
TI  - Involvement of both mitochondrial- and death receptor-dependent apoptotic
      pathways regulated by Bcl-2 family in sodium fluoride-induced apoptosis of the
      human gingival fibroblasts.
AB  - Sodium fluoride (NaF) has been shown to be cytotoxic and produces inflammatory
      responses in humans. However, the cellular mechanisms underlying the NaF-induced
      cytotoxicity in periodontal tissues are unclear. This study examined whether or
      not NaF induces apoptosis in human gingival fibroblasts (HGF), and its underlying
      mechanisms by monitoring various apoptosis-associated processes. NaF reduced the
      cell viability of HGF in a dose- and time-dependent manner. NaF increased TUNEL
      positive cell and induced apoptosis with concomitant chromatin condensation and
      DNA fragmentation in HGF. In addition, NaF increased the level of cytochrome c
      released from the mitochondria into the cytosol, enhanced the caspase-9, -8 and 
      3 activities, the cleavage of poly (ADP-ribose) polymerase (PARP), and up
      regulated the voltage-dependent anion channel (VDAC) 1. However, NaF did not
      affect the production of reactive oxygen species (ROS) which is a strong
      apoptotic inducer. Furthermore, NaF up-regulated the Fas-ligand (Fas-L), a ligand
      of death receptor. Bcl-2, a member of the anti-apoptotic Bcl-2 family, was down
      regulated, whereas the expression of Bax, a member of the pro-apoptotic Bcl-2
      family, was unaffected in the NaF-treated HGF. These results suggest that NaF
      induces apoptosis in HGF through both the mitochondria-mediated pathways
      regulated by the Bcl-2 family and death receptor-mediated pathway.

PMID- 18069114
TI  - The G(-2518)A polymorphism of monocyte chemotactic protein-1 (MCP-1) and its
      serum and peritoneal fluid levels in Korean women with endometriosis.
AB  - OBJECTIVES: To investigate the associations between endometriosis and the G(
      2518)A polymorphism of monocyte chemotactic protein-1 (MCP-1), and serum and
      peritoneal fluid MCP-1 levels in Korean women. STUDY DESIGN: The G(-2518)A
      polymorphism of MCP-1 was analyzed by restriction fragment length polymorphism in
      105 women with and in 101 women without endometriosis. Serum and peritoneal fluid
      MCP-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      The genotype frequencies of the MCP-1 G (-2518)A polymorphism were GG 36.9%, AG
      52.9%, and AA 10.2%. MCP-1 genotype frequencies and serum and peritoneal fluid
      MCP-1 levels were similar in those with or without endometriosis and were not
      dependent on disease stage. A significant correlation was found between serum and
      peritoneal fluid levels of MCP-1. However, no differences were found between MCP
      1 genotypes in terms of serum and peritoneal fluid MCP-1 levels. CONCLUSIONS:
      Serum and peritoneal fluid MCP-1 levels and the G (-2518)A MCP-1 polymorphism
      were found not to be associated with endometriosis in Korean women.

PMID- 18069115
TI  - Structural characterization and low-resolution model of BJ-48, a thrombin-like
      enzyme from Bothrops jararacussu venom.
AB  - Thrombin-like enzymes (TLEs) are important components of snake venoms due to
      their involvement in coagulopathies occurring on envenoming. Structural
      characterization of this group of serine proteases is of utmost importance for
      better understanding their unique properties. However, the high carbohydrate
      content of some members of this group prevents successful crystallization for
      structural determination. Circumventing this difficulty, the structure of BJ-48,
      a highly glycosylated TLE from Bothrops jararacussu venom, was studied in
      solution. At pH 8.0, where the enzyme displays maximum activity, BJ-48 has a
      radius of gyration (Rg) of 37 A and a maximum dimension (D(max)) of 130 A as
      measured by small-angle X-ray scattering (SAXS) and a Stokes radius (SR) of 50 A
      according to dynamic light scattering (DLS) data. At the naturally more acidic pH
      (6.0) of the B. jararacussu venom BJ-48 behaves as a more compact particle as
      evidenced by SAXS (R(g)=27.9 A and D(max)=82 A) and DLS (SR=30 A) data. In
      addition, Kratky plot analysis indicates a rigid shape at pH 8.0 and a flexible
      shape at pH 6.0. On the other hand, the center of mass of intrinsic fluorescence
      was not changed while varying pH, possibly indicating the absence of fluorescent
      amino acids in the regions affected by pH variation. Circular dichroism
      experiments carried out with BJ-48 indicate a substantially random coiled
      secondary structure that is not affected by pH. Low-resolution model of BJ-48
      presented a prolate elongated shape at pH 8.0 and a U-shape at 6.0. BJ-48
      tertiary structure at pH 6.0 was maintained on heating up to 52 degrees C and was
      completely lost at 75 degrees C. The possible existence of two pH-induced folding
      states for BJ-48 and its importance for the biological role and stability of this
      enzyme was discussed.

PMID- 18069116
TI  - Thermodynamic and spectroscopic study for the interaction of dimethyltin(IV) with
      L-cysteine in aqueous solution.
AB  - Thermodynamic and spectroscopic properties of the species formed by
      dimethyltin(IV) cation with L-cysteine (cys) were studied by potentiometric,
      calorimetric, UV and NMR investigations in aqueous solution. The resulting
      speciation model showed the formation of five complex species:
      (CH(3))(2)Sn(cys)H(+), (CH(3))(2)Sn(cys)(0), (CH(3))(2)Sn(cys)OH(-),
      (CH(3))(2)Sn(cys)(2)H(-), (CH(3))(2)Sn(cys)(2)(2-). The stability and the
      formation percentages, for the mononuclear mixed species in particular, are very
      high, in a wide pH range. Thermodynamic parameters indicate that the enthalpy
      values are exothermic and the enthalpic contribution to the stability is higher
      than entropic one. Individual UV spectra of cys and dimethyltin(IV)-cys species
      were calculated. Spectroscopic results of UV and (1)H NMR investigations fully
      confirm the speciation model. The structures calculated from NMR investigations
      show that all the species have an eq-(CH(3))(2)-tbp structure.

PMID- 18069117
TI  - Transurethral photoselective vaporization versus transvesical open enucleation
      for prostatic adenomas >80ml: 12-mo results of a randomized prospective study.
AB  - OBJECTIVES: To compare the effectiveness and the safety of photoselective
      vaporization of the prostate (PVP) to open prostatectomy (OP) for the surgical
      treatment of large prostatic adenomas. METHODS: A total of 125 patients with
      prostate glands >80ml were randomly allocated to PVP (n=65) or OP (n=60) and
      prospectively evaluated at 1, 3, 6, and 12 mo postoperatively. International
      Prostate Symptom Score (IPSS) and peak urinary flow rate (Q(max)) were chosen as
      primary treatment-related end points. RESULTS: The patients who underwent PVP
      experienced a longer length of operation time, shorter time of catheterization,
      and shorter hospital stay. Adverse events were minor and of similar profiles in
      both groups, although patients who underwent OP showed a higher transfusion rate.
      All functional parameters improved significantly compared to baseline values in
      both groups. The IPSS did not differ between the two groups at 3, 6, and 12 mo
      postoperatively. Patients who underwent OP scored better in the IPSS quality of
      life score at 6 and 12 mo postoperatively. No significant differences between the
      two groups in the Q(max), postvoid residual urine volume, and International Index
      for Erectile Function-5 questionnaire were detected. At 3 mo prostate volume was
      significantly lower in the OP group compared to the PVP group (median value 10ml
      vs. 50ml; p<0.001) and remained as such throughout follow-up, whereas prostate
      specific antigen values reached statistical difference at 6 mo (median value
      2ng/ml vs. 2.4ng/ml; p=0.028). CONCLUSIONS: Our results indicate that for a 12-mo
      period PVP is a highly acceptable treatment alternative to OP.

PMID- 18069120
TI  - A novel approach to energy ablative therapy of small renal tumours: laparoscopic
      high-intensity focused ultrasound.
AB  - OBJECTIVE: High-intensity focused ultrasound (HIFU) permits targeted homogeneous
      ablation of tissue. The objective of this phase 1 study was to evaluate the
      feasibility of HIFU ablation of small renal tumours under laparoscopic control.
      PATIENTS AND METHODS: Ten kidneys with solitary renal tumours were treated with a
      newly developed 4.0 MHz laparoscopic HIFU probe. In the first two patients with 9
      cm tumours, a defined marker lesion was placed prior to laparoscopic radical
      nephrectomy. In eight patients with a mean tumour size of 22 mm (range, 11-40),
      the tumour was completely ablated as in curative intent, followed by laparoscopic
      partial nephrectomy in seven tumours. One patient had post-HIFU biopsies and was
      followed radiologically. Specimens were studied by detailed and whole-mount
      histology, including NADH stains. RESULTS: Mean HIFU insonication time was 19 min
      (range, 8-42), with a mean targeted volume of 10.2 cm3 (range, 9-23). At
      histological evaluation both marker lesions showed irreversible and homogeneous
      thermal damage within the targeted site. Of the seven tumours treated and removed
      after HIFU, four showed complete ablation of the entire tumour. Two had a 1- to 3
      mm rim of viable tissue immediately adjacent to where the HIFU probe was
      approximated, and one tumour showed a central area with about 20% vital tissue.
      There were no intra- or postoperative complications related to HIFU. CONCLUSION:
      The morbidity of laparoscopic partial nephrectomy mainly comes from the need to
      incise highly vascularized parenchyma. Targeted laparoscopic HIFU ablation may
      render this unnecessary, but further studies to refine the technique are needed.

PMID- 18069121
TI  - Editorial comment on: transurethral photoselective vaporization versus
      transvesical open enucleation for prostatic adenomas >80ml: 12-mo results of a
      randomized prospective study.

PMID- 18069122
TI  - Editorial comment on: transurethral photoselective vaporization versus
      transvesical open enucleation for prostatic adenomas >80ml: 12-mo results of a
      randomized prospective study.

PMID- 18069123
TI  - KiSS-1 mRNA in adipose tissue is regulated by sex hormones and food intake.
AB  - Hypothalamic KiSS-1 gene expression is critical for the maintenance of
      reproductive function, and levels are attenuated by sex hormones and by food
      restriction, providing a link between fat mass and fertility. We hypothesized
      that adipose tissue (FAT) would express KiSS-1. KiSS-1 mRNA was quantified in
      FAT, hypothalamus (HYP) and pituitary gland (PIT) using realtime RT-PCR. FAT KiSS
      1 expression was sensitive to sex steroids and to nutritional status.
      Gonadectomized rats given estradiol (E; females) or testosterone (T; males)
      revealed striking increases in KiSS-1 mRNA in FAT (E: 8-fold, p<0.01; T: 5-fold,
      p<0.01). In contrast, HYP KiSS-1 expression was reduced by E/T, whereas PIT
      expression was reduced by gonadectomy only in females, reversed by E. Food
      restriction (18 h) increased FAT KiSS-1 mRNA in both sexes (2.5-4.0-fold,
      p<0.01), but decreased levels in male PIT and female HYP. Conversely, FAT
      expression was reduced in rats fed a high fat diet (HFD), as well as in obese
      Zucker rats, whereas PIT expression was increased in Zucker rats (p<0.05) but not
      by HFD. In contrast HYP KiSS-1 mRNA was elevated by HFD. Experiments in which the
      arcuate nucleus was damaged by an excitotoxic lesion revealed that hypothalamic
      KiSS-1 mRNA was significantly reduced, whereas FAT levels were unaffected,
      suggesting that regulation of KiSS-1 in FAT is independent of the hypothalamus.
      In conclusion, KiSS-1 expression is differentially regulated by sex hormones,
      food intake and obesity in FAT, HYP and PIT. Kisspeptins of adipose tissue origin
      may act as adipokines or as local regulators of adipocyte function.

PMID- 18069124
TI  - Broncho-pleural fistula due to trans-diaphragmatic migration of the distal end of
      ventriculo-peritoneal shunt.
AB  - We report two cases of broncho-pleural fistula resulting from trans-diaphragmatic
      migration of the distal catheter of a ventriculo-peritoneal shunt. Relevant
      literature on thoracic complications of a ventriculo-peritoneal shunt is
      reviewed. The clinical presentation, diagnosis and management of V-P shunt
      related broncho-pleural fistulae are discussed.

PMID- 18069125
TI  - Antioxidant and neuroprotective properties of N-arachidonoyldopamine.
AB  - N-Acyldopamines were recently described as putative endogenous substances in the
      rat brain. Among them, N-arachidonoyldopamine (AADA) was characterized as
      cannabinoid CB1 and vanilloid TRPV1 receptor ligand. The physiological
      significance of such compounds is yet poorly understood. In this study, we
      describe the novel properties of AADA as antioxidant and neuroprotectant.
      Antioxidant potential of AADA and its analogs were first tested in the galvinoxyl
      assay. It was found that N-acyldopamines are potent antioxidants and that the
      number of free hydroxyl groups in the phenolic moiety of dopamine is essential
      for the activity. AADA dose dependently (0.1-10 microM) protected cultured
      cerebellar granule neurons (CGN) in the model of oxidative stress induced by
      hydrogen peroxide. N-Oleoyldopamine, another endogenous substance, was much less
      potent in these conditions while the natural antioxidant alpha-tocopherol was
      inactive. In this test, AADA decreased the peroxide level in CGN preparations and
      its neuroprotection was independent of cannabinoid/vanilloid receptors blockade.
      AADA (10 microM) also protected CGN from death induced by K(+)/serum deprivation
      and glutamate exitotoxicity. These data indicate that AADA may act as endogenous
      antioxidant in different pathological conditions.

PMID- 18069126
TI  - Meta-analysis of whole-genome linkage scans for intracranial aneurysm.
AB  - Genetic predisposition likely plays an important role in the development of
      intracranial aneurysms. We carried out a genome search meta-analysis to
      identified loci associated with intracranial aneurysm. We identified previous
      whole-genome linkage analyses by searching PUBMED. Five studies reported by
      separate investigators where detailed data could be obtained were included in our
      analysis. We synthesized the available genome-wide scan data by using a
      heterogeneity-based genome search meta-analyses. We identified two linkage sites
      on chromosomes 3 and 17 which had P-values <0.01 for association with
      intracranial aneurysm. Our findings confirm the association of a locus on
      chromosome 17 and identify a new linkage site on chromosome 3 for intracranial
      aneurysm. The new locus contains a number of potential gene candidates including
      kininogen-1 precursor, fibroblast growth factor-12 and endothelin converting
      enzyme 2.

PMID- 18069128
TI  - Managing patient dose in multi-detector computed tomography(MDCT). ICRP
      Publication 102.
AB  - Computed tomography (CT) technology has changed considerably in recent years with
      the introduction of increasing numbers of multiple detector arrays. There are
      several parameters specific to multi-detector computed tomography (MDCT) scanners
      that increase or decrease patient dose systematically compared to older single
      detector computed tomography (SDCT) scanners. This document briefly reviews the
      MDCT technology, radiation dose in MDCT, including differences from SDCT and
      factors that affect dose, radiation risks, and the responsibilities for patient
      dose management. The document recommends that users need to understand the
      relationship between patient dose and image quality and be aware that image
      quality in CT is often higher than that necessary for diagnostic confidence.
      Automatic exposure control (AEC) does not totally free the operator from
      selection of scan parameters, and awareness of individual systems is important.
      Scanning protocols cannot simply be transferred between scanners from different
      manufacturers and should be determined for each MDCT. If the image quality is
      appropriately specified by the user, and suited to the clinical task, there will
      be a reduction in patient dose for most patients. Understanding of some
      parameters is not intuitive and the selection of image quality parameter values
      in AEC systems is not straightforward. Examples of some clinical situation shave
      been included to demonstrate dose management, e.g. CT examinations of the chest,
      the heart for coronary calcium quantification and non-invasive coronary
      angiography, colonography, the urinary tract, children, pregnant patients, trauma
      cases, and CT guided interventions. CT is increasingly being used to replace
      conventional x-ray studies and it is important that patient dose is given careful
      consideration, particularly with repeated or multiple examinations.

PMID- 18069127
TI  - A novel TRH analog, Glp-Asn-Pro-D-Tyr-D-TrpNH2, binds to [3H][3-Me-His2]TRH
      labelled sites in rat hippocampus and cortex but not pituitary or heterologous
      cells expressing TRHR1 or TRHR2.
AB  - Glp-Asn-Pro-D-Tyr-D-TrpNH(2) is a novel synthetic peptide that mimics and
      amplifies central actions of thyrotropin-releasing hormone (TRH) in rat without
      releasing TSH. The aim of this study was to compare the binding properties of
      this pentapeptide and its all-L counterpart (Glp-Asn-Pro-Tyr-TrpNH(2)) to TRH
      receptors in native rat brain tissue and cells expressing the two TRH receptor
      subtypes identified in rat to date, namely TRHR1 and TRHR2. Radioligand binding
      studies were carried out using [(3)H][3-Me-His(2)]TRH to label receptors in
      hippocampal, cortical and pituitary tissue, GH4 pituitary cells, as well as CHO
      cells expressing TRHR1 and/or TRHR2. In situ hybridization studies suggest that
      cortex expresses primarily TRHR2 mRNA, hippocampus primarily TRHR1 mRNA and
      pituitary exclusively TRHR1 mRNA. Competition experiments showed [3-Me-His(2)]TRH
      potently displaced [(3)H][3-Me-His(2)]TRH binding from all tissues/cells
      investigated. Glp-Asn-Pro-D-Tyr-D-TrpNH(2) in concentrations up to 10(-5)M did
      not displace [(3)H][3-Me-His(2)]TRH binding to membranes derived from GH4 cells
      or CHO-TRHR1 cells, consistent with its lack of binding to pituitary membranes
      and TSH-releasing activity. Similar results were obtained for the corresponding
      all-L peptide. In contrast, both pentapeptides displaced binding from rat
      hippocampal membranes (pIC(50) Glp-Asn-Pro-D-Tyr-D-TrpNH(2): 7.7+/-0.2; pIC(50)
      Glp-Asn-Pro-Tyr-TrpNH(2): 6.6+/-0.2), analogous to cortical membranes (pIC(50)
      Glp-Asn-Pro-D-Tyr-D-TrpNH(2): 7.8+/-0.2; pIC(50) Glp-Asn-Pro-Tyr-TrpNH(2): 6.6+/
      0.2). Neither peptide, however, displaced [(3)H][3-Me-His(2)]TRH binding to CHO
      TRHR2. Thus, this study reveals for the first time significant differences in the
      binding properties of native and heterologously expressed TRH receptors. Also,
      the results raise the possibility that Glp-Asn-Pro-D-Tyr-D-TrpNH(2) is not
      displacing [(3)H][3-Me-His(2)]TRH from a known TRH receptor in rat cortex, but
      rather a hitherto unidentified TRH receptor.

PMID- 18069129
TI  - Dronedarone in atrial fibrillation.

PMID- 18069130
TI  - Shattuck Lecture: improving American health.

PMID- 18069131
TI  - Shattuck Lecture: improving American health.

PMID- 18069132
TI  - Shattuck Lecture: improving American health.

PMID- 18069133
TI  - Myocardial reperfusion injury.

PMID- 18069134
TI  - Myocardial reperfusion injury.

PMID- 18069135
TI  - Myocardial reperfusion injury.

PMID- 18069136
TI  - Myocardial reperfusion injury.

PMID- 18069137
TI  - [54th meeting of the Japanese Society of Clinical Pathology. Osaka, Japan.
      November 22-25, 2007. Program and Abstracts].

PMID- 18069138
TI  - [In "referred cases" the points must be shared].

PMID- 18069139
TI  - [Children with attention deficit hyperactivity disorder in school].
AB  - To keep secondary disorders to a minimum, the early diagnosis and treatment of
      ADHD and its possible comorbidities is important. Aside from the care of a
      specialist, several additional measures permit the integration of these children
      into a structured everyday school routine and thus also permit age-appropriate
      development.

PMID- 18069140
TI  - [New drug agreement stands. No more deductions starting next year].

PMID- 18069141
TI  - [Turner syndrome in adulthood].

PMID- 18069143
TI  - 'Simple surfing' where people can get information on health.

PMID- 18069142
TI  - Reliability and normative values of the foot line test: a technique to assess
      foot posture.
AB  - STUDY DESIGN: Test-retest reliability. OBJECTIVE: To examine the reliability and
      report normative values of a novel test, the foot line test (FLT), to describe
      foot morphology. BACKGROUND: Numerous foot examinations are performed each day,
      but most existing examination techniques have considerable limitations regarding
      reliability and validity. METHODS: One hundred thirty subjects with mean foot
      size 44 (41-50 European size) participated. Two examiners, blinded to each
      other's measurements, measured the right foot of the subjects twice and the left
      foot once. The position of the most medial aspect of the navicular in the
      mediolateral direction was projected vertically onto a piece of paper placed
      under the subject's foot, and compared to the position of the forefoot and
      hindfoot to obtain the FLT value. RESULTS: FLT values ranged from -8 to 14 mm,
      with a mean (+/-SD) of 3.7 +/- 3.4 mm. The intratester reproducibility reported
      by SEM was 0.8 mm for tester 1 and 0.9 mm for tester 2, while intertester SEM was
      1.4 mm for the right foot and 1.3 mm for the left foot. The intrarater ICC was
      0.95 for tester 1 and 0.94 for tester 2, while the interrater ICC was 0.86 (left
      foot) and 0.83 (right foot). There was no significant association between foot
      size and FLT values. CONCLUSION: The FLT is a reproducible technique to assess
      foot posture.

PMID- 18069144
TI  - TN: Pt. fell & died from complications of surgery: was nursing negligence cause
      of patient's fall? Vaughn v. John W. Harton Regional Med. Center, 2007 TNCIV
      M2006-01326-COA-R3 (09/21/07) S,W.3d -TN.

PMID- 18069145
TI  - Learning on the Web. Case 2: patent foramen ovale (PFO) and paradoxical embolism.
AB  - A 36 year old woman ruptured her right Achilles tendon in a skiing accident.
      Previous medical history is unremarkable except for a history of migraine for
      many years. She is married with three children with no history of spontaneous
      miscarriage. She smokes 15 cigarettes a day and takes the oral contraceptive
      pill. She is admitted to a local hospital where surgery to repair the Achilles
      tendon is performed followed by fitting of a plaster cast. Due to pain from the
      plaster cast she is slow to mobilise. On day 7 postoperatively she develops
      increasing pain in the right leg. When the plaster is removed the right calf is
      found to be painful, warm, and swollen. The next day while straining on the
      toilet she collapsed with left arm weakness. Clinical examination revealed
      dysarthria with pyramidal weakness of the left arm. The significance of these
      symptoms, the diagnosis, and the short and long term treatment of these
      postoperative problems are discussed in an interactive case presentation.

PMID- 18069146
TI  - Learning on the Web. Case 3: acute chest pain.
AB  - A 49 year old Afro-Caribbean woman presents to A&E after a 30 minute episode of
      severe, burning central chest pain radiating to the throat. When she had the pain
      she felt cold and sweaty but is now symptom-free. Episodes of a similar but less
      severe pain had occurred daily for the previous 10 days, predominantly at rest
      but also when climbing the stairs at home. The patient has multiple risk factors
      for coronary disease (including type II diabetes, hypertension, and being a
      smoker), but the clinical presentation is not absolutely typical for coronary
      artery disease and the initial ECG is normal. There is also a history from the
      patient of an exercise stress test one week before, which she believed to be
      normal. The significance of these signs and symptoms, the diagnosis, and the
      short and long term treatment of these problems are discussed in an interactive
      case presentation.

PMID- 18069147
TI  - Panel backs AIDS drugs.

PMID- 18069148
TI  - IAS 2007--Sydney conference update.

PMID- 18069149
TI  - Highlights of biomedical prevention strategies. Methods to prevent HIV from the
      angle of biology offer hope. IAS 2007-Sydney conference update.

PMID- 18069150
TI  - HIV treatment series. Metabolic complications myths. Some misunderstandings about
      treatment.

PMID- 18069151
TI  - Getting things done. Americorps National AIDS Fund. AmeriCorps program offers
      invaluable training while providing service to HIV/AIDS community.

PMID- 18069152
TI  - TH9507: an experimental treatment for lipodystrophy.
AB  - As the use of highly active antiretroviral therapy (HAART) became widespread, HIV
      positive individuals and their physicians began to notice changes in body fat
      distribution, with excess fat or fat loss noted in different areas. These body
      shape changes are sometimes accompanied by metabolic abnormalities, such as
      insulin resistance and elevated blood fats. Collectively, these changes are known
      as lipodystrophy syndrome. Treatment options for lipodystrophy are somewhat
      limited. Growth hormone has been used with success in clinical trials to reduce
      visceral adipose tissue, fat that collects around the abdominal organs. A new
      product, TH9507, a synthetic growth hormone releasing hormone analog made by the
      Canadian pharmaceutical company Theratechnologies, is currently showing promise
      in clinical trials and may represent a new treatment option for people with some
      types of lipodystrophy.

PMID- 18069153
TI  - Skin and soft tissue infections caused by community-acquired methicillin
      resistant Staphylococcus aureus.
AB  - Skin and soft tissue infections (SSTI) are a source of significant illness and
      accounted for over 2 million visits to emergency room departments in the United
      States in 2004. While most infections are minor and do not require
      hospitalization, some can be life-threatening--particularly for people living
      with HIV.

PMID- 18069154
TI  - Renal complications of HIV/AIDS.
AB  - Renal complications are common among people living with HIV; in fact, up to 30%
      of HIV positive individuals may have protein in their urine--a sign of kidney
      dysfunction. It is difficult to estimate precisely how many people develop kidney
      disease--and, therefore, to implement effective disease prevention or early
      intervention--because kidney dysfunction may be asymptomatic or may result in
      only vague symptoms, such as fatigue or general malaise. Without specific
      symptoms, many individuals are diagnosed later in their disease course, reducing
      the efficacy of available treatments. Given the risks associated with kidney
      disease, developing awareness of kidney function and getting the necessary tests
      are essential to maintaining good health with HIV. This article explains how
      kidney function is assessed, describes the renal complications that are most
      commonly seen in HIV positive people, and outlines treatment options.

PMID- 18069155
TI  - Human papillomavirus.
AB  - A majority of sexually active adults carry the human papillomavirus (HPV), but
      until recently, this virus received little public attention. This changed in 2006
      with the approval of a new vaccine that can prevent infection with certain types
      of HPV, and thereby reduce the risk of cervical cancer.

PMID- 18069156
TI  - On the road with HIV: a guide for positive travelers.

PMID- 18069158
TI  - Metformin does not harm diabetic patients with heart failure.

PMID- 18069157
TI  - Course is benign for uncomplicated diverticular disease.

PMID- 18069159
TI  - Does race affect a patient's response to antihypertensives?

PMID- 18069161
TI  - Pneumonia: 3 to 5 days of antibiotics is as effective as 10 days.

PMID- 18069160
TI  - Respiratory infection: patient satisfaction not linked to Rx writing.

PMID- 18069162
TI  - Evolving treatment of biliary strictures following liver transplantation.
AB  - BACKGROUND: The optimal endoscopic treatment for anastomotic biliary strictures
      after deceased donor liver transplantation is undefined. Endoscopic therapy with
      conventional methods of biliary dilation and stent placement has been successful
      but often requires prolonged therapy. OBJECTIVE: To determine the outcomes of an
      aggressive endoscopic approach that uses endoscopic dilation followed by maximal
      stent placement. SETTING: Tertiary-care academic medical center. PATIENTS: Of 176
      patients who underwent deceased donor liver transplantation between June 1999 and
      July 2004, 25 were diagnosed with anastomotic biliary strictures. INTERVENTIONS:
      Patients were treated endoscopically with a combined technique of balloon
      dilation and maximal stent placement. MAIN OUTCOME MEASUREMENTS: Treatment
      outcomes, including bileduct patency, a need for surgical intervention,
      morbidity, and mortality, were evaluated retrospectively. RESULTS: Endoscopic
      dilation followed by maximal stent placement was performed until resolution of
      strictures in 22 or 25 patients (88% immediate success on intent-to-treat
      analysis). Persistent resolution of strictures was achieved in 18 of these 22
      patients. Re-treatment was successful in 2 of 4 patients with recurrent
      strictures. Overall, 20 or 22 patients who completed endoscopic therapy (91%)
      avoided surgical intervention. Medical duration of endoscopic treatment was 4.6
      months. Patients with early onset strictures required a significantly shorter
      duration of endoscopic therapy (3 vs 9 months; P < .01). Multiple stent placement
      was not technically difficult, and no major complications were encountered.
      CONCLUSIONS: Aggressive endoscopic therapy with combined biliary dilation and
      maximal stent placement allows resolution of anastomotic biliary strictures after
      deceased donor liver transplantation in a relatively short period, with sustained
      success and minimal complications.

PMID- 18069163
TI  - [Dr. Agustin Chardi Cordova (1917-2007)].

PMID- 18069164
TI  - [Mexican Council of Orthopedics and Traumatology A.C].

PMID- 18069165
TI  - [Presentation of the Medical Ethics Code of the Mexican Orthopedics Society,
      A.C].

PMID- 18069166
TI  - Pathologic findings in racing pigeons (Columba livia domestica) with "young bird
      sickness".
AB  - "Young bird sickness" is a term used by racing pigeon fanciers to describe a
      condition that has occurred regularly in recent years and affects pigeons
      (Columba livia domestica) in their first year of life. It is characterized by
      slow crop emptying, regurgitation, diarrhea, weight loss, poor performance, and
      occasionally death. Little scientific information is known about this syndrome to
      differentiate it from other diseases that occur in young pigeons. In this study,
      1 bird from each of 9 lofts where "young bird sickness" was reported was
      euthanatized for cytologic and postmortem examination. Lesions of the
      lymphoreticular system, alimentary tract, and respiratory system were the most
      common findings. Lesions of the lymphoreticular system were present in all birds
      examined, and 3 birds had histopathologic findings consistent with circovirus
      infection. Combinations of protozoal, fungal, and mixed bacterial infections were
      associated with ingluvitis in 7 birds and enteritis in 6 birds. Pneumonitis was
      found in 5 birds that tested positive for Chlamydophila by polymerase chain
      reaction. Although "young bird sickness" appears to be a multifactorial
      condition, a pattern of lesions that involved the lymphoreticular,
      gastrointestinal, and respiratory systems was evident, whereas diseases of other
      organ systems were uncommon. These findings suggest that "young bird sickness"
      may have a common etiology, and circovirus infection is proposed as a possible
      initiating cause of this syndrome in young racing pigeons in Northern Ireland.

PMID- 18069167
TI  - Urinalysis as a noninvasive health screening procedure in Falconidae.
AB  - Clinical signs of renal disorders in animals, including raptors, are not
      specific. Furthermore, serum or plasma biochemical parameters change only when
      70% of kidney function is lost. In this study, reference values of urine
      variables were established in clinically healthy falcons. Urine samples were
      collected from 78 mature (> 1 year) and immature (6-12 months) male and female
      falcons belonging to 5 species. Droppings were assessed visually for urate color
      and consistency and color of the liquid urine. The liquid urine was collected by
      aspiration into a syringe and centrifuged, and the supernatant analyzed by
      commercial dipstick and by a wet chemistry analysis for alkaline phosphatase,
      gamma glutamyl transferase, glucose, chloride, and total protein concentrations.
      Sex, age, and species did not affect results of biochemical urine values (P >
      .05). Urine biochemical values did not differ significantly between fasted and
      fed birds. Total protein levels in urine samples decreased after 24-hour storage
      at 4 degrees C. Reference ranges for clinically normal birds are reported.

PMID- 18069168
TI  - Inflammatory reaction to fabric collars from percutaneous antennas attached to
      intracoelomic radio transmitters implanted in harlequin ducks (Histrionicus
      histrionicus).
AB  - In wild birds implanted intracoelomically with radio transmitters, a synthetic
      fabric collar placed around the base of a percutaneous antenna is believed to
      function as a barrier to contamination of the coelom. We examined 13 fabric
      collars recovered from percutaneous antennas of radio transmitters implanted
      intracoelomically in harlequin ducks (Histrionicus histrionicus) 12 months
      earlier. Both the transmitters and antenna collars were encapsulated in fibrous
      connective tissue, with adhesions to internal organs. Histologically, bacteria
      were evident at the fabric-plastic interface in 8 of 10 collars examined in cross
      section and along the length of the collar in 3 collars examined longitudinally.
      Bacteria were confined within the fibrotic sheath surrounding the transmitter and
      the antenna collar in all birds. No evidence of chronic systemic effects
      secondary to implantation was present on hematologic or serum biochemical
      testing. These findings indicate that antenna collars do not prevent the entry of
      bacteria along the percutaneous antenna but may help stabilize the antenna and
      minimize coelomic contamination. We conclude that radio transmitters implanted
      into the coelom of harlequin ducks do not appear to cause significant health
      problems for at least 1 year after implantation.

PMID- 18069169
TI  - Endoscopic orchidectomy and salpingohysterectomy of pigeons (Columba livia): an
      avian model for minimally invasive endosurgery.
AB  - To evaluate a minimally invasive endosurgical system in birds, endoscopic
      orchidectomy and salpingohysterectomy were evaluated in 11 male and 14 female
      pigeons (Columba livia). Anesthesia was maintained by using isoflurane delivered
      by a pressure-cycle ventilator and produced good to excellent anesthesia during
      96% of procedures. Endosurgery was performed with a 2.7-mm telescope system, 3-mm
      human pediatric laparoscopy instruments, and a 4.0-MHz radiofrequency device.
      Mean +/- SD surgery times for bilateral orchidectomy and salpingohysterectomy
      procedures were 39 +/- 18 minutes and 34 +/- 15 minutes, respectively. Procedures
      were generally straightforward, with any minor complications easily overcome.
      Surgical complications were generally minor, with mild hemorrhage and focal
      coagulative damage to the kidney being most common. All pigeons recovered quickly
      (20 +/- 11 minutes), with 95% displaying good to excellent recoveries. No birds
      exhibited any clinically apparent morbidity or mortality associated with
      endosurgery. At least 1 male and 1 female bird were subjected to elective
      euthanasia and necropsy on postoperative days 1, 3, 5, 10, 20, and 90 to
      determine the success and side effects of surgery. Gross and histologic
      abnormalities, when observed, were generally mild, with hemorrhage and partial
      necrosis of the cranial kidney present in 27% of males. Mild damage or hematoma
      associated with the left kidney was also reported in 28% of females. The surgical
      objectives were achieved in 23 of 25 pigeons. The 2 surgical failures
      (regenerated testes in a male and large oviductal remnant in a female) were
      attributed to endosurgical inexperience and occurred during the first procedures.
      Salpingohysterectomy does not appear to prevent ovarian development and ovulation
      in the pigeon, at least not during the first 3 postoperative months. Orchidectomy
      and salpingohysterectomy appear to be safe procedures when performed using
      appropriate equipment and techniques. Endosurgery offers a valuable, minimally
      invasive alternative to the standard coeliotomy techniques commonly used in
      birds.

PMID- 18069170
TI  - Internal anatomy of the hornbill casque described by radiography, contrast
      radiography, and computed tomography.
AB  - Hornbills are distinguished from most other avian taxa by the presence of a
      casque on the dorsal maxillary beak, which, in all but 1 of the 54 extant
      hornbill species, is described as essentially an air-filled cavity enclosed by
      minimal cancellous bone. The external casque has been described in detail, but
      little has been described about its internal anatomy and the communications
      between the casque and the paranasal sinuses. In this study, 10 intact casque and
      skull specimens of 7 hornbill species were collected opportunistically at
      necropsy. The anatomy of the casque and the skull for each of the specimens was
      examined by radiography, contrast radiography, and computed tomography. After
      imaging, 8 specimens were submitted for osteologic preparation to directly
      visualize the casque and the skull interior. Through this standardized review,
      the baseline anatomy of the internal casque was described, including
      identification of a novel casque sinus within the paranasal sinus system. These
      observations will assist clinicians in the diagnosis and treatment of diseases of
      the casque in hornbill species.

PMID- 18069172
TI  - Radiographic evidence of atherosclerosis of the descending aorta in a grey
      cheeked parakeet (Brotogeris pyrrhopterus).
AB  - A 16-year-old male grey-cheeked parakeet (Brotogeris pyrrhopterus) was presented
      for dyspnea and decreased activity. The bird's diet was primarily table food,
      with a large proportion of animal products. Radiographs revealed a linear
      mineralized structure in the plane of the aorta and an enlarged hepatocardiac
      silhouette. Left atrial and left ventricular enlargement and a left ventricular
      systolic dysfunction were diagnosed by echocardiography. The bird's condition
      progressively declined, and it died 5 days after presentation. A postmortem
      examination revealed marked atherosclerosis of the aorta, great vessels of the
      heart, and coronary arteries with myocardial degeneration, pulmonary congestion,
      and ascites. Little is known about the risk factors of atherosclerosis in
      psittacine birds, and dietary influence, if any, is not understood.

PMID- 18069171
TI  - Avipoxvirus infection in a collection of captive stone curlews (Burhinus
      oedicnemus).
AB  - A natural outbreak of avipoxvirus occurred in recently purchased stone curlews
      (Burhinus oedicnemus) at a breeding farm and subsequently spread to other stone
      curlews residing at the farm. The initial outbreak was characterized by mild
      vesicular skin lesions on the legs, which then developed crusts and bled. The
      overall morbidity rate was 100%, but none of the birds died, and all recovered
      without complication. Four gallinaceous species, also kept on the farm, did not
      develop lesions. Avipoxvirus was identified from the skin lesions by virus
      isolation, electron microscopy, and monoclonal antibody testing, as well as by
      polymerase chain reaction testing. Eight months after this outbreak, 7 male stone
      curlews developed large, round, crusty lesions on their legs. Although poxvirus
      virions were identified in the lesions, results of virus isolation were negative.
      These lesions possibly were the result of a recrudescence of the original
      infection in male birds that were stressed because they were housed together
      during the breeding season. This is the first clinical description of an
      avipoxvirus infection in stone curlews.

PMID- 18069173
TI  - Veterinary contributions to wildlife biology: participation in avian field
      studies in Alaska.
AB  - This report describes the author's experiences in participating in avian research
      during 3 field seasons in remote areas in Prince William Sound (PWS), located in
      south-central Alaska. Veterinary support was needed to biopsy the livers of
      nestling and adult pigeon guillemots (Cepphus columba) and adult black
      oystercatchers (Haematopus bachmani). These surgeries were part of larger
      research studies investigating guillemot and oystercatcher populations and
      possible continued exposure to residual crude oil in the marine environment after
      the Exxon Valdez oil spill in PWS in 1989.

PMID- 18069174
TI  - The pet store client: making this relationship work.

PMID- 18069175
TI  - What is your diagnosis? Subcutaneous foreign-material granuloma.

PMID- 18069176
TI  - Insomnia cure still sought.

PMID- 18069177
TI  - More supernumeraries?

PMID- 18069178
TI  - Clinical and microbiological effects of topical minocycline in the treatment of
      elderly patients with periodontitis.
AB  - OBJECTIVE: To evaluate a 2% w/w minocycline gel (Dentomycin) in the treatment of
      older adults with chronic periodontitis. DESIGN: Vehicle-controlled, split-mouth
      SETTING: Dental Institute, St Bartholomew's and the Royal London School of
      Medicine and Dentistry. SUBJECTS: 22 adults (mean age 60 years). INTERVENTIONS:
      At baseline, patients received scaling and root planing. Test and placebo were
      applied at contralateral disease sites surrounding 22 test and 22 control teeth
      at baseline, and at weeks 2 and 4. MAIN OUTCOME MEASURE: Probing pocket depth,
      bleeding on probing and supragingival plaque measurements, and microbiological
      sampling, at one pocket site per tooth were undertaken at baseline, and at weeks
      2, 4, 6 and 16. RESULTS: Microbial counts of Porphyromonas gingivalis, Prevotella
      intermedia and Eikenella corrodens did not change significantly over 16 weeks. No
      significant reductions in bleeding on probing and supragingival plaque score
      occurred with either gel. A larger reduction in mean pocket depth, from baseline
      to week 16, was found at test (6.50 to 4.95 mm; 24% reduction; P < 0.01) than at
      control sites (6.41 to 5.53 mm; 14% reduction; P < 0.05). CONCLUSIONS:
      Minocycline gel administration is a useful adjunct to scaling and root planing in
      the treatment of older adults with periodontitis.

PMID- 18069179
TI  - A dental support group for anxious patients.
AB  - OBJECTIVE: To evaluate, qualitatively, a support group for dentally anxious
      patients reluctant to visit the dentist and obtain dental care. DESIGN: Semi
      structured interviews by group discussion, face-to-face or telephone. SETTING:
      Community: primary health care centre. SUBJECTS: 14 (50%) of the members of the
      support group. INTERVENTIONS: 13 interviewees were also monitored during a course
      of treatment following support group attendance. MAIN OUTCOME MEASURES: Views of
      interviewees concerning dental attendance and dental care before, during and
      after attendance at the support group. RESULTS: Attendance at the group was a
      major factor in dispelling fears and negative beliefs about dental care. The 13
      interviewees whose progress was monitored through a subsequent course of
      treatment had a mean age of 43 years and had last attended for dental care 9
      years previously. Treatment lasted for a mean of 5.4 visits with few failed
      appointments. They showed a significant (P < 0.01) reduction in Corah dental
      anxiety scale score. CONCLUSIONS: Attendance at the support group generated
      empathy between members and confidence to seek treatment. It increased trust in
      the dental team but tended to lead to dependence on the dentist group leader.
      Wider availability of such groups could help to reduce dental anxiety in non
      attending adults and encourage treatment uptake.

PMID- 18069180
TI  - A preliminary report of a case using an intra-oral distraction device.
AB  - A case is reported where the callus in a mandibular osteotomy site underwent
      distraction by means of an intra-oral device. The procedure was undertaken in a 9
      year-old patient diagnosed with hemifacial microsomia type I. Using rapid
      prototyping from a radiographic scan of the facial skeleton an acrylic model was
      made upon which the intra-oral appliance was designed. The appliance produced an
      elongation of 11 mm which succeeded in correcting the skeletal asymmetry of the
      mandibular symphysis. The patient has been followed up for 7 months and the
      correction appears stable.

PMID- 18069181
TI  - Conventional retreatment versus surgery in failed root canal treatment--the
      importance of canal anatomy.
AB  - This case report highlights two important aspects of root canal treatment,
      knowledge of root canal anatomy and inappropriate use of surgery to correct
      failure of conventional treatment. Initially, two mandibular incisors were root
      treated conventionally but only one of the two canals present in both teeth was
      prepared and filled in each case. Symptoms persisted and a surgical approach was
      adopted but, again, only one of the root canals in each tooth was located and
      sealed with a root-end filling. Surgery was performed on a second occasion but
      again failed to resolve the patient's problems. On referral, the presence of the
      additional root canals was confirmed and further conventional non-surgical
      treatment resulted in the immediate cessation of symptoms. This case highlights
      the need for a thorough understanding of root canal morphology, and the need to
      expose an angled radiograph when performing root canal therapy on teeth with a
      high incidence of multiple canals. It emphasises that surgery should not be the
      first option when conventional treatment fails.

PMID- 18069182
TI  - Sharps injuries involving a sheathed needle.
AB  - Two dental nurses each sustained a sharps injury while attempting to remove the
      sheathed needle from a used dental local anaesthetic syringe. The needle had been
      bent inadvertently during use. Neither of the dental nurses were aware that the
      needle had perforated the side of the sheath during resheathing. This incident
      emphasises the need for constant vigilance during the disposal of sharps and for
      the routine avoidance of direct contact with sheathed or unsheathed needles and
      other sharps after use.

PMID- 18069183
TI  - Are nice dentists purely fictional?
AB  - Fiction dentists, particularly the nice ones, give a neat image of what patients
      expect from us, for their creators are intrinsically sensitive to people's
      feelings. The few exemplary readings which follow show that, both through
      negative and positive images of dentistry, the basic message we get from many
      writers is that dentistry should be performed properly and painlessly.

PMID- 18069184
TI  - Tinker, tailor, soldier, dentist.

PMID- 18069185
TI  - [Diagnosis at a glance. Patient wants no operation. Only a cosmetic disorder?].

PMID- 18069186
TI  - [Adult patient with chronic cough of unknown origin. This can also be whooping
      cough].

PMID- 18069187
TI  - [Sudden confusion in a multi-morbid diabetic patient. Blood glucose was not the
      cause].

PMID- 18069188
TI  - [Forty years after the introduction of the first antihypertensives. Hypertension
      treatment is still not optimal].

PMID- 18069189
TI  - [Hypertension therapy--never without diuretics?].
AB  - Diuretics are highly effective and are valuable antihypertensives in modern high
      blood pressure therapy. As a monotherapy, diuretics should be preferably be used
      in elderly patients; in a combination therapy, in any case in a triple
      combination therapy, they should be used regardless of the patient's age.
      Disadvantages include risk for developing hypokalaemia, their diabetogenicity
      with unclear long-term prognosis and the usually limited treatment persistence.
      Diuretics are no longer the lowest-priced antihypertensives. For monotherapy and
      dual combination therapy, effective alternatives are available. The necessity for
      the use of diuretics cannot be rationalized either medically or economically.

PMID- 18069190
TI  - [Are beta blockers no longer the medicines of choice for the treatment of
      hypertension?].
AB  - Intervention studies indicate that beta blockers as well as diuretics have
      unfavourable effects on lipid metabolism and lead to new onsets of diabetes
      mellitus more frequently than ACE inhibitors, AT1 antagonists and calcium
      antagonists. Moreover, a meta-analysis showed an elevated risk for strokes in
      hypertensive patients treated with beta blockers. Until the conclusion of other
      controlled studies, beta blockers will nevertheless retain their important role
      in the treatment of hypertensive patients with coronary heart disease or heart
      failure. They should continue to be one of the preferred antihypertensives.

PMID- 18069191
TI  - [Taking blood pressure in the presence of atrial fibrillation].
AB  - Measuring the blood pressure of patients with atrial fibrillation is difficult
      due to the high variability of the blood pressure. To obtain a representative
      average, the blood pressure should be measured as often as possible. Each blood
      pressure measurement should be repeated at least three times in succession.

PMID- 18069192
TI  - [Therapy-resistant hypertension--the value of aldosterone antagonists].
AB  - Uncontrolled studies suggest the benefits of an add-on antihypertensive therapy
      with an aldosterone receptor antagonist. However, it still must be clarified
      whether a PHA screening has a predictive value for the efficacy of a therapy with
      an aldosterone receptor antagonist. Before generally accepted recommendations can
      be made, a randomized, controlled study with aldosterone antagonists must prove
      that such a therapy is safer, tolerable and leads to better long-term blood
      pressure control as well as lower renal and cardiovascular morbidity and
      mortality.

PMID- 18069193
TI  - [Alternative methods for wound treatment].

PMID- 18069194
TI  - [Emergency checklist: acute pilonidal sinus].

PMID- 18069195
TI  - [New effective dosage of valsartan. High dosage--effective against high blood
      pressure].

PMID- 18069196
TI  - [Risk oriented therapy of hypertension. Lowering blood pressure and risk].

PMID- 18069199
TI  - The other side of nursing.

PMID- 18069200
TI  - GreenLight laser: BPH treatment shows promise.

PMID- 18069201
TI  - Tipping the scales. What nurses need to know about the childhood obesity
      epidemic.

PMID- 18069202
TI  - To your benefit.

PMID- 18069203
TI  - Starting your workout safely.

PMID- 18069204
TI  - Good debt vs. bad debt.

PMID- 18069205
TI  - The eyes have it. A young patient's journey back from spinal cord injury.

PMID- 18069206
TI  - [The importance of screening for thyroid dysfunction during pregnancy:
      pathophysiological background and practical implications].
AB  - Thyroid hormones are essential both for the physiological course of pregnancy and
      for the optimal differentiation of the embryonic tissues and foetal brain
      development. Overt and subclinical hypothyroidism constitutes a frequent cause of
      infertility, it carries along an increased risk of spontaneous abortion and
      premature birth, and it may lead to an impaired foetal brain development
      resulting in a worse psychoneurological outcome in the progeny. The repeatedly
      documented high prevalence of thyroid diseases in pregnancy warrants a
      realization of systematic screening for thyroid dysfunction during early stage of
      pregnancy or better before conception whenever possible. The Czech Endocrine
      Society attempts to implement such a systematic screening in the Czech Republic,
      although the particular aspects of the screening are still discussed.

PMID- 18069207
TI  - [Reflection on the physiological mechanisms of movements controlled by the spinal
      cord-brain interaction].
AB  - The process of communication between brain and spinal cord remains unclear.
      Therefore an attempt supported by spinal cord stereotaxy was made to disclose the
      physiological mechanism underlying the cooperation between brain and spine as
      generated by the spinal cord. The initializing stimulus was the discovery of
      motoneuron location in all spinal cord segments providing the organic substrate
      for spinal cord stereotaxy. What remained to be clarified were the anatomical
      structures of spinal cord, participating in the feedback between brain and spinal
      cord. Therefore two possible hypotheses were proposed by the authors. One is
      closely related to the analytic-synthetic mechanism of real object and thoughts
      depiction in the memory of the brain and in the form of concrete ideas forming
      the basis for concrete thinking. In the case of spinal cord, another more
      probable mechanism should be considered: The process of analysis and synthesis
      between the participating spinal motoneurons. The mutual neuronal connections in
      the spinal cord are capable of depicting the movement pattern and the movement is
      transferred by means of the described spinal cord pathways to the memory of the
      brain as a concrete movement idea. From here the ideas are transferred according
      to the individual needs backwards by means of another described spinal cord
      pathways back to the spinal cord and the spinal cord is the final effector. The
      process of thinking is the physiological correlate of technical software, but in
      the form of abstract thinking it is transferred to the form of abstract thinking.

PMID- 18069208
TI  - [Nutrigenetics and nutrigenomics].
AB  - According to WHO reports diet factors influence occurrence of more than 2/3 of
      diseases. Most of these factors belong to the categories of nutrigenetics a
      nutrigenomics. Nutrigenetics concerns individual differences in the reaction to
      food based on the genetic factors. Nutrigenomics analyses direct influences of
      nutrients on gene expression. Both terms are explained in our review article.
      Importance of nutritional factors is explained on differences of epidemiology of
      the same disease in different countries and on the examples of interaction of
      nutrition and genes for hypertension, atherosclerosis and cancer. In the future
      both, nutrigenetics a nutrigenomics, will induce many changes in preventive and
      also in clinical medicine.

PMID- 18069209
TI  - [The interpreter role of clinical geneticist in the process of genetic testing].
AB  - Due to the progress in genetic research, development and rapid introduction of
      new genetic tests into clinical practise can be expected. This is raising many
      ethical issues which need to be carefully considered. First, genetic information
      is a familial. Thus, the test result of one person may have direct health
      implications for others who are genetically related. Second, the risks of genetic
      testing are also psychological, social and financial. Third, due to complex ways
      of genes interactions, genetic information often has limited predictive power.
      Finally, many genetic conditions remain difficult to treat or prevent, meaning
      the value of genetic information may be limited for altering the clinical care
      for the person. Given these concerns, detailed counselling and informed consent
      should be key aspects of genetic testing process. Genetic counselling in Czech
      Republic is provided by clinical geneticist. Therefore he is playing a key role
      in addressing these issues to patients. His second role is to interpret the
      genetic information revealed in genetic testing into the language understandable
      for patient, which means translation of genetic data into diagnosis and clinical
      management of individual, a transformation from statistics to physical persons.
      This interpretation is determining many aspects of patient's future life (future
      planning, reproductive decisions, prevention, health behaviour, etc.) and also
      family attitudes towards testing. The importance of genetic counselling, informed
      consent process and precise interpretation of results will be increasing over the
      time when new generation of genetic technologies for detecting the common
      conditions will be introduced into the practise.

PMID- 18069210
TI  - [Silent ischemia and noisy stunning: a perspective of the cause and hints of
      associations].
AB  - The significance of ST-segment changes in an electrocardiogram need not be always
      as clear-cut as we used to think. Minor problems usually represent only the ST
      segment depressions in the presence of typically manifested problems and
      established coronary artery disease. The same holds true for ST-segment
      elevations: in addition, they definitively superior to ST-segment depressions.
      Among other categories, silent ischemia denotes only a part of what is or can be
      seen. This article deals with other conditions associated with changes in ST
      segments and variable symptoms with changeable clinical implications.

PMID- 18069211
TI  - [Thrombophilia in pregnancy--physiology and pathophysiology of hemocoagulation
      changes during normal and pathological gravidity].
AB  - Venous thromboembolism belongs to most feared complications in pregnancy. It is
      the leading cause of illness and even death during pregnancy and puerperium.
      Thrombophilias--acquired or inherited, manifest often during pregnancy and
      puerperium. These risk states could endanger normal pregnancy by increasing the
      probability of the first or recurrent thromboembolic incident and adverse
      obstetric events (pregnancy loss, pre-eclampsia, intrauterine growth restriction,
      placental abruption).

PMID- 18069212
TI  - [Milestones of cardiovascular therapy. V. Diuretics].
AB  - After their introduction in 1959, thiazide diuretics have become the cornerstone
      in the managment of heart failure and hypertension. They prevent sodium
      reabsorption in the upper segment of the distal tubule, increase the diuresis
      and, by diminishing the intravascular volume, they reduce the preload. With
      vigorous diuresis, cardiac output may drop under the critical level, and
      hypovolaemia, hypotension, syncopes and dehydratation with severe water-mineral
      disturbance may occur. A similar disorder takes place after aggressive
      administration of loop diuretics which act by the same mechanism at the ascending
      limb of the loop of Henle. Moreover, any chronic treatment with saluretics
      triggers the contraregulatory activation of RAAS. Thus, the dosing should be
      cautiously titrated, and with diminishing efficacy the diuretic is to be replaced
      by another one, or a second drug is to be added. With any potent diuretic agent,
      electrolyte depletion may occur; therefore, minimal active doses should be
      applied, potassium-sparing diuretics added or a pause should be inserted
      after/before furosemide with spirolactone. Hyponatraemia and hypokalaemia are
      common, and in combined treatment with ACE-inhibitors and spirolactone,
      hyperkalaemia is frequent. With long-term treatment, a rebound period of sodium
      reabsorption follows, and the diuretic effect is reduced or lost. To overcome
      this ",diuretic resistance", the dietary sodium is to be restricted, physical
      effort avoided and salt retaining drugs (NSAIDs and similar) eliminated. In the
      article, a short review of basic physiology concerning the water-electrolyte
      balance and the distribution of body-water is summarized.

PMID- 18069213
TI  - [Significance of serum antibodies ANCA, ASCA, ABBA in diagnostics of idiopathic
      intestinal inflammations].
AB  - BACKGROUND: Crohn's disease and ulcerative colitis still remain a heterogeneous
      group of diseases with an unclear aetiology. Serologic methods play important
      role in their diagnosing though there is still not an ideal marker. We tried to
      determine the importance of serological testing of ASCA IgA, IgG, ANCA, ABBA
      antibodies in patients with ulcerative colitis and Crohn's disease. METHODS AND
      RESULTS: ASCA IgG, ASCA IgA; ANCA, ABBA antibodies and C-reactive protein were
      detected by indirect fluorescence assay. ASCA IgA, ASCA IgG, ABBA, ANCA were
      examined in 40 patients (28 Crohn's disease, 12 ulcerative colitis, 32 health
      controls). Specificity of ASCA IgA, IgG in CD patients was high (both 96.2%),
      specificity ANCA in UC 100%. ABBA antibodies had low sensitivity and specificity
      in both diseases. Combination of ASCA, ANCA, ABBA makes the specificity higher.
      CONCLUSIONS: We showed the importance of combination ASCA, ANCA with ABBA
      antibodies to improve the serological diagnosing of IBD.

PMID- 18069214
TI  - [Pilot study to evaluate blood glucose control by a model predictive control
      algorithm with variable sampling rate vs. routine glucose management protocol in
      peri- and postoperative period in cardiac surgery patients].
AB  - BACKGROUND: Increased blood glucose levels are frequently observed in critically
      ill patients. Recent studies have shown that the normalization of glycemia by
      intensive insulin therapy decreases mortality, length of the hospitalization and
      number of complications. METHODS AND RESULTS: The aim of this pilot study was to
      compare blood glucose control by an automated model predictive control algorithm
      with variable sampling rate (eMPC) with routine glucose management protocol (RP)
      in peri- and postoperative period in cardiac surgery patients. 20 patients were
      included into this study (14 men and 6 women, mean age 68 +/- 10 let, BMI 28.3 +/
      5.0 kg/m2). 10 patients were randomized for treatment using eMPC algorithm and
      10 patients for routine protocol. All patients underwent elective cardiac surgery
      and were treated with continuous insulin infusion to maintain glycemia in target
      range 4.4-6.1 mmol/l. The study duration was 24 hours. Mean blood glucose was
      significantly lower in eMPC vs. RP group (5.80 +/- 0.45 vs. 7.23 +/- 0.84 mmol/l,
      p < 0.05). Percentage of time in target range was significantly higher in eMPC
      vs. RP group (67.6 +/- 8.7% vs. 27.6 +/- 15.8%, p < 0.05). Percentage of time
      above the target range was higher in RP vs. eMPC group. Average insulin infusion
      rate was higher in eMPC vs. RP group (4.18 +/- 1.19 vs. 3.24 +/- 1.43 IU/hour, p
      < 0.05). Average sampling interval was significantly shorter in eMPC vs. RP group
      (1.51 +/- 0.24 vs. 2.03 +/- 0.16 hour, p < 0.05). No severe hypoglycaemia in
      either group occurred during the study. CONCLUSIONS: The results of our pilot
      study suggest that eMPC algorithm is more effective in maintaining euglycemia in
      peri- and post-operative period in patients after cardiac surgery and comparably
      safe as compared to RP.

PMID- 18069215
TI  - [Changes of plasminogen activator inhibitor (PAI-1) during estrogen replacement
      therapy].
AB  - BACKGROUND: The purpose of the present study was to determine changes of
      plasminogen activator inhibitor-1 (PAI-1) as biochemical cardiovascular risk
      factor during the use of different administration methods in the early estrogen
      replacement therapy. METHODS AND RESULTS: In a 12-week prospective, randomized,
      interventional, cross-over trial, oestradiol was administered orally in a dose of
      2 mg daily or transdermally in a dose of 0.05 mg daily. Forty-five healthy
      postmenopausal women were included into the study within 12 weeks after the
      hysterectomy and ovariectomy (surgical castration). Forty-one women completed the
      study and their data were analyzed. The average age was of 49 +/- 6 years. PAI-1
      was determined by bioimmunoassay (Chromolyze PAI-1). The PAI-1 level decreased
      statistically significantly (p = 0.001) after the oral oestrogen therapy from
      11.39 +/- 12.02 IU/l to 5.0 +/- 5.27 IU/l. Changes are also significant compared
      with non-significant changes after the transdermal therapy. CONCLUSIONS: The oral
      therapy reduced statistically significantly PAI-1 levels compared with the
      transdermal method of administration. This change is beneficial from the view of
      cardiovascular risk.

PMID- 18069216
TI  - [Tachycardia-induced cardiomyopathy].
AB  - Tachycardia-induced cardiomyopathy is characterised with a ventricular
      dysfunction caused by increased ventricular rate. It is a reversible mechanism of
      the heart failure. Cardiomyopathy can recover after the restoration of sinus
      rhythm or after adjusting the heart rate. In the presented paper we are
      discussing ethiopathogenesis, diagnostics and therapy of tachycardia-induced
      cardiomyopathy and we are describing the case of a patient with this diagnosis,
      who was admitted to our department.

PMID- 18069217
TI  - [Repeated thrombosis of the mechanical heart valve prosthesis].
AB  - Paper presents the cause of 54-year-old patient with implanted mechanical heart
      valve prosthesis in the mitral position admitted to the hospital with a serious
      left ventricle (LV) systolic dysfunction. Patient underwent repeated attacks of
      acute left-sided heart insufficiency on the basis of verified thrombosis of the
      mechanical heart valve prosthesis. Pharmacological treatment was not effective
      and the systemic thrombolysis failed. Patient was twice reoperated--thrombectomy
      was performed during the first surgery, mechanical heart valve prosthesis was
      replaced with biological prosthesis during the second one. Patient was
      permanently treated with anticoagulants. The combination of bioprosthesis in the
      mitral position with the anticoagulant treatment appears to be a final therapy of
      the patient.

PMID- 18069219
TI  - [Multiple skin papules of the axilla. What metabolic disorder should be
      considered?].

PMID- 18069220
TI  - [Because public health policy saves on diagnosis. "Salmonella infection
      undiagnosed and transmitted" (interview by Dr. Judith Neumaier)].

PMID- 18069221
TI  - [Gentle methods for early intestinal cancer diagnosis. Conventional colonoscopy-
      an obsolete model?].

PMID- 18069222
TI  - [Lower LDL and/or raise HDL. In what direction is lipidology moving?].

PMID- 18069223
TI  - [LDL cholesterol--why lower and lower?].
AB  - Large interventional studies with statins have confirmed that drug-lowering of
      LDL cholesterol by at least 25-30% is associated with a significant reduction in
      the cardiovascular risk. In high-risk patients, the plasma LDL cholesterol level
      should be < 100 mg/dl. If the levels are initially low, the aim is to achieve a
      reduction of at least 30-40%. More recent studies have shown that reducing the
      LDL cholesterol to < 70 mg/dl can stop the further growth of plaques, and can
      possibly even bring about their regression.

PMID- 18069224
TI  - [Assessing the risk of HDL cholesterol].
AB  - Low HDL cholesterol levels represent a significant cardiovascular risk factor.
      HDL not only has a central role in the reverse transport of cholesterol but,
      independently of this, presumably also has anti-oxidative, anti-inflammatory,
      antithrombotic and endothelium-regulating properties. The reasons for lowered HDL
      cholesterol levels are manifold (genetic inheritance, life style). Measures with
      an influence on life style can have a decisive impact on the HDL cholesterol
      level. Medication-based options are much less well established, and the clinical
      endpoints less well investigated than the corresponding options for LDL-lowering
      drug therapies. Among the drugs currently available, niacin has the most
      pronounced HDL-elevating effect.

PMID- 18069225
TI  - [Precancerous or squamous cell carcinoma? How to recognize and correctly classify
      sun-damaged skin].

PMID- 18069226
TI  - [Cosmetic surgery of the head and neck area].
AB  - In addition to face lifting, facial surgery includes measures such as forehead
      and brow lifting, rhinoplasty, eyelid lifts, liposuction, laser resurfacing and
      filler and botulinum toxin treatments. The respective indications, risks and
      contraindications are described.

PMID- 18069227
TI  - [Every dyspnea without plausible etiology is suspicious. Early pulmonary artery
      hypertension diagnosis!].

PMID- 18069228
TI  - [Selective vasodilation in the lung. Sildenafil improves physical capacity and
      prognosis].

PMID- 18069229
TI  - [IGeL in family practice. How to keep it from becoming a practice burden?].

PMID- 18069230
TI  - [Medical continuing education in other European countries. Finance office cannot
      simply classify as vacation].

PMID- 18069231
TI  - [Current renumeration counseling. A systematic review of vaccination status is
      worthwhile].

PMID- 18069232
TI  - Structural studies of native Paecilomyces sp. Exopolysaccharide.
AB  - A polysaccharide separated from Paecilomyces sp. was determined by gel permeation
      chromatography to be homogeneous. HPLC showed a monosaccharide containing D
      glucose and D-fructose at a ratio of about 2:1. The results obtained from IR, 1H
      NMR, and 13C NMR analyses confirmed the proposed structure.

PMID- 18069233
TI  - Alkaloid variability in Leucojum aestivum from wild populations.
AB  - Leucojum aestivum (summer snowflake) is a plant species used for the extraction
      of galanthamine, an acetylcholinesterase inhibitor for the treatment of
      Alzheimer's disease. Extracts from bulbs collected from 18 Bulgarian populations
      and from shoot-clumps obtained in vitro from 8 different populations showed
      variations in their alkaloid composition. Nineteen alkaloids were detected in the
      studied samples by GC-MS. Typically, the alkaloid fractions of L. aestivum bulbs
      were dominated by galanthamine type compounds, but lycorine, haemanthamine and
      homolycorine type alkaloids were also found as dominant compounds in some of the
      samples. Extracts from the shoot-clumps obtained in vitro were found to contain
      galanthamine or lycorine as main alkaloids. The galanthamine content ranged from
      28 to 2104 microg/g dry weight in the bulbs, and from traces to 454 microg/g dry
      weight in the shoot-clumps.

PMID- 18069234
TI  - Phenolic compound profiles and their corresponding antioxidant Capacity of purple
      pitaya (Hylocereus sp.) genotypes.
AB  - Folin-Ciocalteu and TEAC (Trolox equivalent antioxidant capacity) assay together
      with the spectrophotometric determination of betalains were applied to
      investigate the correlation between phenolics and their contribution to the
      antioxidant capacity of five different Costa Rican genotypes of purple pitaya
      (Hylocereus sp.) and of H. polyrhizus fruits. Maximum antioxidant capacity, total
      phenolic and betalain contents were observed in the genotype 'Lisa'. While non
      betalainic phenolic compounds contributed only to a minor extent, betalains were
      responsible for the major antioxidant capacity of purple pitaya juices evaluated.
      The phenolic pattern of each genotype was also thoroughly investigated using
      liquid chromatography coupled to positive electrospray ionization (ESI) tandem
      mass spectrometry. In addition to the well known betalains previously reported in
      Hylocereus fruits, several biosynthetic precursors were detected. Notably,
      decarboxylated and dehydrogenated betalains were identified as genuine compounds
      of the juices. Some of these compounds were previously described as artifacts
      upon heat exposure. Moreover, gallic acid was identified for the first time in
      pitaya fruits. While the phenolic profiles generally differed between genotypes,
      phenolic compound composition of 'Rosa' resembled that of H. polyrhizus with
      respect to total contents of betacyanins, betalainic precursors, phyllocactin and
      cyclo-Dopa malonyl-glucosides.

PMID- 18069235
TI  - Effect of Egyptian propolis on the susceptibility of LDL to oxidative
      modification and its antiviral activity with special emphasis on chemical
      composition.
AB  - The antioxidant activity of eight Egyptian propolis samples from different
      localities was evaluated by the antioxidative potential and capacity of the DPPH
      ESR signal, superoxide anion generated in the xanthine-xanthine oxidase (XOD)
      system and low density lipoprotein (LDL) peroxidation assay. As, F, Is and D
      samples showed the highest antioxidative capacity and potential, respectively.
      The El, IsR, Is, D and So samples exhibited highly significant antioxidant
      activity in the XOD system and in LDL peroxidation assays. The antiviral activity
      of propolis samples was investigated. They showed variations in their activity;
      sample D induced the highest antiviral activity against Newcastle disease virus
      and infectious bursal disease virus. 42 Polyphenolic compounds were identified by
      HPLC; 13 aromatic acids, esters and alcohols were present, 29 flavonoids were
      identified, 6 of them being new to propolis.

PMID- 18069236
TI  - Evaluation of cytotoxic compounds from calligonum comosum L. growing in Egypt.
AB  - Calligonum comosum (Polygonaceae), an Egyptian desert plant, was extracted and
      fractionated using petroleum ether, methylene chloride, and ethyl acetate. The
      total methanolic extract and other fractions were tested for their anticancer
      activity using Ehrlich ascites, brine shrimp and antioxidant assays. Ethyl
      acetate fraction proved to be the most active in all assays. Eight compounds were
      isolated, purified, and identified from this fraction as (+)-catechin (1),
      dehydrodicatechin A (2), kaempferol-3-O-rhamnopyranoside (3), quercitrin
      (quercetin-3-O-rhamnopyranoside) (4), beta-sitosterol-3-O-glucoside (5),
      isoquercitrin (quercetin-3-O-glucopyranoside) (6), kaempferol-3-O-glucuronide
      (7), and mequilianin (quercetin-3-O-glucuronide) (8). All isolated compounds were
      tested for their cytotoxicity and antioxidant activity. Compound 2 showed the
      best cytotoxic and antioxidant activity.

PMID- 18069237
TI  - Phytochemical and molluscicidal investigations of Fagonia arabica.
AB  - The aqueous methanolic extract of the aerial parts of Fagonia arabica L. (family
      Zygophyllaceae) was successively fractionated using certain organic solvents.
      From the ethyl acetate fraction, two flavonoid glycosides were isolated and
      identified as kaempferol-7-O-rhamnoside and acacetin-7-O-rhamnoside. Four
      triterpenoidal glycosides were isolated from the butanolic layer. Their
      structures were elucidated on the basis of the spectral and chemical data as 3-O
      beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinopyranoside oleanolic acid (1), 3-O
      alpha-L-arabinopyranosyl quinovic acid 28-O-beta-D-glucopyranoside (2), 3-O-[beta
      D-glucopyranosyl-(1-->2)]-beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinosyl
      oleanolic acid (3) and 3-O-beta-D-glucopyranosyl-(1-->3)-alpha-L-arabino
      pyranosyl quinovic acid 28-O-beta-D-glucopyranoside (4). The two monodesmosidic
      saponins 1 and 3 were found to possess strong molluscicidal activity against
      Biomphalaria alexandrina snails, the intermediate host of Schistosoma mansoni in
      Egypt (LC90 = 13.33 and 16.44 microM), whereas the other two bidesmosidic
      saponins 2 and 4 as well as the two flavonoid glycosides were inactive up to 50
      microM.

PMID- 18069238
TI  - Antibacterial activity of triterpene acids and semi-synthetic derivatives against
      oral pathogens
AB  - Triterpene acids (ursolic, oleanoic, gypsogenic, and sumaresinolic acids)
      isolated from Miconia species, along with a mixture of ursolic and oleanolic
      acids and a mixture of maslinic and 2-a-hydroxyursolic acids, as well as ursolic
      acid derivatives were evaluated against the following microorganisms:
      Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Streptococcus
      salivarius, Streptococcus sobrinus, and Enterococcus faecalis, which are
      potentially responsible for the formation of dental caries in humans. The
      microdilution method was used for the determination of the minimum inhibitory
      concentration (MIC) during the evaluation of the antibacterial activity. All the
      isolated compounds, mixtures, and semi-synthetic derivatives displayed activity
      against all the tested bacteria, showing that they are promising antiplaque and
      anticaries agents. Ursolic and oleanolic acids displayed the most intense
      antibacterial effect, with MIC values ranging from 30 microg/mL to 80 microg/mL.
      The MIC values of ursolic acid derivatives, as well as those obtained for the
      mixture of ursolic and oleanolic acids showed that these compounds do not have
      higher antibacterial activity when compared with the activity observed with
      either ursolic acid or oleanolic acid alone. With regard to the structure
      activity relationship of triterpene acids and derivatives, it is suggested that
      both hydroxy and carboxy groups present in the triterpenes are important for
      their antibacterial activity against oral pathogens.

PMID- 18069239
TI  - Screening for free radical scavenging and cell aggregation inhibitory activities
      by secondary metabolites from Turkish Verbascum species.
AB  - Free radical scavenging and cell aggregation inhibitory activities of 36
      secondary metabolites isolated from the methanolic extracts of Verbascum
      cilicicum Boiss., V. lasianthum Boiss. ex Bentham, V pterocalycinum var. mutense
      Hub.-Mor., and V. salviifolium Boiss. (Scrophulariaceae) were investigated. The
      isolated compounds, 6-O-vaniloyl ajugol (1), ilwensisaponin A (2), ilwensisaponin
      C (3), verbascoside (4), beta-hydroxyacteoside (5), martynoside (6), poliumoside
      (7), forsythoside B (8), angoroside A (9), dehydrodiconiferyl alcohol-9-O-beta-D
      glucopyranoside (10), dehydrodiconiferyl alcohol-9'-O-beta-D-glucopyranoside
      (11), apigenin 7-O-beta-glucopyranoside (12), luteolin 7-O-beta-glucopyranoside
      (13), luteolin 3'-O-beta-glucopyranoside (14) and chrysoeriol 7-O-beta
      glucopyranoside (15), exhibited a dose-dependent inhibition of bioautographic and
      spectrophotometric DPPH activities. Verbascoside (4) was the most active (IC50
      4.0 microg/ml) comparing it to vitamin C (IC50 4.4 microg/ml) to inhibit phorbol
      12-myristate 13-acetate (PMA)-induced peroxide-catalyzed oxidation of 2',7'
      dichlorofluorescein (DCFH) by reactive oxygen species (ROS) within human
      promyelocytic HL-60 cells. Ilwensisaponin A (2) (MIC 6.9 microg/ml) showed
      moderate in vitro activity on lymphocyte-associated antigen-1 (LFA
      1)/intercellular adhesion molecule-1 (ICAM-1)-mediated aggregation using the HL
      60 cell line [positive control was cytochalasin B (MIC 2.3 microg/ml)]. None of
      the other compounds showed free radical scavenging and cell aggregation
      inhibitory activities.

PMID- 18069240
TI  - A comparative study on the genotoxic effect of pyrimethamine in bone marrow and
      spermatogonial mice cells.
AB  - Pyrimethamine is an antimalarial agent widely used in clinical therapy. We aimed
      to compare its mutagenic potential in mammalian spermatogonial and bone marrow
      cells. For studying chromosomal aberrations mice were treated acutely (single
      treatment) with 4 dose levels of pyrimethamine (5, 10, 20 and 40 mg/kg).
      Pyrimethamine was found to produce a significant increase in structural
      chromosomal aberrations after acute treatment in bone marrow cells of mice (p <
      0.001). It also induced chromosome abnormalities in spermatogonial cells (p <
      0.05) at the highest dose.

PMID- 18069241
TI  - In vitro anticholinesterase activity of various alkaloids.
AB  - In the current study, a number of alkaloids including retamine, cytisine, and
      sparteine (quinolizidine-type), yohimbine and vincamine (indole-type),
      scopolamine and atropine (tropane-type), colchicine (tropolone-type), allantoin
      (imidazolidine-type), trigonelline (pyridine-type) as well as octopamine,
      synephrine, and capsaicin (exocyclic amine-type) were tested in vitro for their
      inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase
      (BChE) at 1 mg/ml concentration by the Ellman method using an ELISA microplate
      reader. Among the alkaloids tested, only capsaicin exerted a remarkable
      inhibitory effect towards both AChE and BChE [(62.7 +/- 0.79)% and (75.3 +/-
      0.98)%, respectively]. While the rest of the alkaloids did not show any
      significant inhibition against AChE, three of the alkaloids, namely retamine,
      sparteine, and yohimbine, exerted a noteworthy anti-BChE effect as compared to
      galanthamine, the reference drug.

PMID- 18069242
TI  - Inhibition of acetylcholinesterase by extracts and constituents from Angelica
      archangelica and Geranium sylvaticum.
AB  - The aim of this study was to explore the acetylcholinesterase (AChE) inhibition
      of several Icelandic medicinal herbs. Ethanolic extracts of Angelica archangelica
      seeds and the aerial parts of Geranium sylvaticum proved effective, with IC50
      values of 2.20 mg/ml and 3.56 mg/ml, respectively. The activity of imperatorin
      and xanthotoxin from A. archangelica was measured. Xanthotoxin proved much more
      potent than imperatorin, with an IC50 value of 155 microg/ml (0.72 mM) but that
      for imperatorin was above 274 microg/ml (1.01 mM). However, furanocoumarins seem
      to have a minor part in the total activity of this extract. Synergistic
      interaction was observed between the extracts of A. archangelica and G.
      sylvaticum. Several medicinal herbs (Achillea millefolium, Filipendula ulmaria,
      Thymus praecox and Matricaria maritima) did not show AChE inhibitory activity.

PMID- 18069243
TI  - A structure-activity relationship study on a natural germination inhibitor, 2
      methoxy-4-vinylphenol (MVP), in wheat seeds to evaluate its mode of action.
AB  - The first aim of the present study was to evaluate which structural elements of
      the 2-methoxy-4-vinylphenol (MVP) molecule (1) are responsible for its observed
      activity as germination inhibitor in wheat seeds. To find its mode of action, a
      series of compounds with varying functional moieties and substitution patterns
      were prepared and evaluated for their inhibitory activity. This systematic
      competitive inhibition study characterized two criteria for the effective
      increase of the inhibiting ability: (i) ortho substitution to each of the hydroxy
      and methoxy groups; (ii) alkene moiety on the ring. Understanding how the
      structure of natural compounds relates to their inhibition function is
      fundamentally important and may help to facilitate their application as novel
      inhibitors to restrain preharvest sprouting (PHS) in wheat fields. In this
      regard, in MVP and its natural analogues 8 and 9 as the most active inhibitors,
      the ortho substitution of hydroxy and methoxy groups plays a key role in their
      activity and, as well, the alkene moiety influences the activity significantly.

PMID- 18069244
TI  - Seasonal and intraspecific varation of flavonoids and proanthocyanidins in
      Cecropia glaziovi sneth. Leaves from native and cultivated specimens.
AB  - Cecropia glaziovi Sneth. (syn. C. glaziovii, C. glazioui) (Cecropiaceae) is a
      South American medicinal plant whose antihypertensive activity is attributed to
      its flavonoid and proanthocyanidin contents. The seasonal and intraspecific
      variations of these two classes of compounds in C. glaziovi leaves were assayed
      by spectrophotometry in samples of young and mature leaves collected from native,
      cultivated and micropropagated trees in the dry and rainy periods of the year.
      The total flavonoid and proanthocyanidin contents ranged from (0.64 +/- 0.21)% to
      (3.44 +/- 0.45)% and (2.23 +/- 0.92)% to (5.36 +/- 0.95)%, respectively, among
      the assayed populations. The flavonoid contents in native plants did not differ
      statistically between young and mature leaves within the same season, whereas it
      was higher in both young and mature leaves collected in the dry compared to those
      collected in the rainy period. For cultivated specimens, the results pointed to
      higher contents in the dry season, whereas no significant difference was observed
      for leaves of micropropagated (clone) plants collected in both periods. For the
      assayed populations, higher proanthocyanidin contents were found in the dry
      season, excepting the micropropagated (clone) plants, whose contents did not
      differ significantly between the dry and the rainy periods. Leaves of
      micropropagated (clone) and cultivated specimens showed less intraspecific
      variation in the flavonoid and proanthocyanidin contents than those from native
      trees. These features suggest that, as expected, cultivation of C. glaziovi is of
      great interest providing raw herbal material of better uniform quality.

PMID- 18069245
TI  - Anacardic acids and ferric ion chelation.
AB  - 6-Pentadeca(e)nylsalicylic acids isolated from the cashew Anacardium occidentale
      L. (Anacardiaceae), commonly known as anacardic acids, inhibited the linoleic
      acid peroxidation catalyzed by soybean lipoxygenase-1 (EC 1.13.11.12, type 1)
      competitively without prooxidant effects. Their parent compound, salicylic acid,
      did not have this inhibitory activity up to 800 pm, indicating that the
      pentadeca(e)nyl group is an essential element to elicit the activity. The
      inhibition is attributed to its ability to chelate iron in the enzyme. Thus,
      anacardic acids chelate iron in the active site of the enzyme and then the
      hydrophobic tail portion slowly begins to interact with the hydrophobic domain
      close to the active site. Formation of the anacardic acids-ferric ion complex was
      detected in the ratio of 2:1 as the base peak in the negative ion electrospray
      ionization mass spectrometry. Hence, anacardic acids inhibit both Eox and Ered
      forms.

PMID- 18069246
TI  - Influence of EDTA on lead transportation and accumulation by Sedum alfredii
      hance.
AB  - Hydroponics and pot experiments were conducted to study the effects of
      ethylenediaminetetraacetic acid (EDTA) on Pb transportation and accumulation by
      two contrasting ecotypes of Sedum alfredii Hance. In hydroponics experiments, the
      accumulating ecotype (AE) showed more ability to tolerate Pb toxicity compared
      with the non-accumulating ecotype (NAE). When treated with equimolar mixtures of
      EDTA and Pb, maximum Pb accumulation occurred without any phytotoxicity symptoms.
      Pot experiments with Pb contents of 400 mg kg-1 showed that 5 mM EDTA is the
      optimum dose for the phytoextraction of soils contaminated with relatively low Pb
      levels; in contrast, increasing EDTA addition resulted in increased Pb
      accumulation in the shoots of AE in soils with high Pb content (1200 mg kg(-1)).
      The post-harvest effects of EDTA on available Pb were strong compared with those
      without addition of EDTA (CK). Within the initial 7 days almost no differences of
      water-soluble Pb were noted in soils contaminated with both levels of Pb but
      after 2 weeks, water-soluble Pb started to decrease significantly compared with
      before. Considering the toxicity and biodegradability of synthetic chelators, it
      can be concluded that the chelate-assisted technique is more suitable for soils
      contaminated with low Pb levels and to avoid environment risks; a suitable dose
      of chelators must be considered before application.

PMID- 18069247
TI  - Vulgarenol, a sesquiterpene isolated from Magnolia grandiflora, induces nitric
      oxide synthases II and III overexpression in guinea pig hearts.
AB  - Vulgarenol, a sesquiterpene isolated from Magnolia grandiflora flower petals,
      decreased coronary vascular resistance in the Langendorff isolated and perfused
      heart model, when compared to the control group [(15.2 x 10(7) +/- 1.0 x 10(7))
      dyn s cm(-5) vs. (36.8 x 10(7) +/- 1.2 x 10(7)) dyn s cm(-5)]. Our data suggest
      that this coronary vasodilator effect probably involved inducible and endothelial
      nitric oxide synthase overexpression (6.8 and 4.2 times over control,
      respectively), which correlated with increases in nitric oxide release [(223 +/-
      9) pmol mL(-1) vs. (61 +/- 11) pmol mL(-1)] and in cyclic guanosine monophosphate
      production [(142 +/- 8) pmol mg(-1) of tissue vs. (44 +/- 10) pmol mg(-1) of
      tissue], as compared to control values. This effect was antagonized by 3 microm
      gadolinium(III) chloride, 100 microM N-nitro-L-arginine methyl ester, and 10
      microM 1H-[1,2,4]oxadiazolo[4,2-a]quinoxalin-1-one. Hence, the vulgarenol
      elicited coronary vasodilator effect could be mediated by the nitric oxide
      soluble guanylyl cyclase pathway.

PMID- 18069248
TI  - Biosynthesis of chlorogenic acids in growing and ripening fruits of Coffea
      arabica and Coffea canephora plants.
AB  - Chlorogenic acids are major secondary metabolites found in coffee seeds. The
      accumulation of chlorogenic acids and free quinic acids was studied in Coffea
      arabica cv. Tall Mokka and Coffea canephora seeds. Growth stages are specified
      from I to V, corresponding to rapid expansion and pericarp growth (I), endosperm
      formation (II), mature (green) (III), ripening (pink) (IV), and fully ripened
      (red) (V) stages. We detected monocaffeoylquinic acids (3CQA, 4CQA and 5CQA),
      dicaffeoylquinic acids (3,4diCQA, 3,5diCQA and 4,5diCQA) and a monoferuloylquinic
      acid (5FQA) in whole fruits (stage I), pericarps and seeds. The most abundant
      chlorogenic acid was 5CQA, which comprised 50-60% of the total of C. arabica and
      45-50% of C. canephora seeds. The content of dicaffeoylquinic acid, mainly 3,5
      diCQA, was high in C. canephora. A high content of 5FQA was found in seeds of
      stages III to V, especially in C. canephora. Total chlorogenic acids were
      accumulated up to 14 mg per fruit in C. arabica and 17 mg in C. canephora,
      respectively. In contrast, free quinic acid varied from 0.4-2.0 mg (C. arabica)
      and 0.2-4.0 mg (C. canephora) per fruit during growth. High biosynthetic activity
      of 5CQA, which was estimated via the incorporation of [U-14C]phenylalanine into
      chlorogenic acids, was found in young fruits (perisperm and pericarp) in stage I,
      and in developing seeds (endosperm) in stages II and III. The biosynthetic
      activity of chlorogenic acids was clearly reduced in ripening and ripe seeds,
      especially in C canephora. Transcripts of PAL1, C3'H and CCoAMT, three genes
      related to the chlorogenic acid biosynthesis, were detected in every stage of
      growth, although the amounts were significantly less in stage V. Of these genes,
      CCoAMT, a gene for FQA biosynthesis, was expressed more weakly in stage I. The
      transcript level of CCoAMT was higher in seeds than in pericarp, but the reverse
      was found in PAL1. The pattern of expression of genes for the CQA and FQA
      synthesis is roughly related to the estimated biosynthetic activity, and to the
      accumulation pattern of chlorogenic acids.

PMID- 18069249
TI  - Inheritance and expression of transgenes through anther culture of transgenic hot
      pepper.
AB  - Anther cultures have been developed from transgenic donor peppers carrying HPT/J1
      1. Eight out of sixteen plants produced from an anther culture set pepper fruits.
      Southern blot analysis of donors revealed two independent plants with a single
      copy of the integrated transgene. PCR and RT-PCR results showed the inheritance
      of HPT/J1-1 and expression of J1-1 in A1. All A1 progeny derived from transgenic
      anthers had resistance to hygromycin. They grew normally and showed similar
      phenotypes to the wild-type. Therefore, the use of an anther culture system
      coupled with genetic transformation in breeding programs will greatly facilitate
      the genetic improvement of pepper plants.

PMID- 18069250
TI  - Genetic differentiation among populations of Cicerbita alpina (L.) Wallroth
      (asteraceae) in the western Alps.
AB  - In this study we analyzed the genetic population structure of the hygrophilous
      tall-herb Cicerbita alpina in the western Alps because this group of mountain
      plants is underrepresented in the biogeographical literature. AFLP (amplified
      fragment length polymorphism) fingerprints of 40 samples were analyzed from four
      populations situated in a transect from the southwestern Alps to the eastern part
      of the western Alps and one population from the Black Forest outside the Alps.
      Two genetic groups can be distinguished. The first group (A) comprises the
      populations from the northern and eastern parts of the western Alps, and the
      second group (B) comprises the populations from the southwestern Alps and the
      Black Forest. Group A originates most likely from at least one refugium in the
      southern piedmont regions of the Alps. This result provides molecular evidence
      for a humid climate at the southern margin of the Alps during the Wurm
      glaciation. Group B originates presumably from western or northern direction and
      we discuss two possible scenarios for the colonization of the Alps, i.e. (1) long
      distance dispersal from southwestern refugia and (2) colonization from nearby
      refugia in the western and/or northern Alpine forelands. The study demonstrates
      that the target species harbours considerable genetic diversity, even on a
      regional scale, and therefore is a suitable model for phylogeographic research.

PMID- 18069251
TI  - Phylogenetic analysis of lichen-forming fungi Rhizoplaca zopf from China based on
      ITS data and morphology.
AB  - A molecular phylogenetic analysis of Rhizoplaca melanophthalma, Rhizoplaca
      chrysoleuca, Rhizoplaca peltata and Rhizoplaca haydenii is presented based on the
      nuclear ribosomal internal transcribed spacer (ITS) regions and morphology.
      Rhizoplaca species were collected at 3400-3900 m in Tianshan Mountains, Xinjiang
      province, China. Rhizoplaca haydenii is reported for the first time in China.
      Maximum parsimony (MP) analysis of ITS sequences obtained from Tianshan Mountains
      samples and GenBank reveals that the evolution relationship of Rhizoplaca
      melanophthalma and Rhizoplaca chrysoleuca is closer to each other than to
      Rhizoplaca peltata, and Rhizoplaca haydenii showed closer relatedness to
      Rhizoplaca melanophthalma. When the four species groups from Tianshan Mountains
      were analyzed alone through the neighbour-joining (NJ) and minimum evolution
      method, we obtained the same result. The morphology analysis of Rhizoplaca Zopf
      which reveals the pruinose discs and apothecial discs of species did not show
      convincing evidences to prove phylogenetic relationship among Rhizoplaca species
      In our study, the result further proved that Rhizoplaca should be rejected as a
      genus separate from Lecanora.

PMID- 18069252
TI  - Heterologous expression of SARS-CoV ORF10 and X5 genes in E. coli and
      Streptomyces lividans TK24.
AB  - In previous studies a variety of novel accessory genes has been identified that
      were interspersed among the structural genes of the SARS-CoV (severe acute
      respiratory syndrome coronavirus) genome. The predicted unknown proteins (PUPs)
      encoded by the accessory genes, which are considered to be unique to the SARS-CoV
      genome, might play important roles in the SARS-CoV infection. Two of these genes,
      called ORF10 and X5, were synthesized and introduced into E. coli and
      Streptomyces lividans TK24, respectively. SDS-PAGE and Western blot revealed that
      the ORF10 and X5 genes have been expressed in the two hosts. This is the first
      report of heterologous expression of ORF10 and X5 genes in E. coli and S.
      lividans TK24. This work makes it possible to study the structure and potential
      functions of proteins encoding by these two genes.

PMID- 18069254
TI  - [Morphology and growth mechanism of myeloma cells].

PMID- 18069253
TI  - Species spectrum of flea beetles (Phyllotreta spp., Coleoptera, Chrysomelidae)
      attracted to allyl isothiocyanate-baited traps.
AB  - In field tests in Hungary, Slovenia and Bulgaria, in allyl isothiocyanate-baited
      traps significantly more beetles of Phyllotreta cruciferae, Ph. vittula, Ph.
      undulata, Ph. nigripes, Ph. nodicornis, Ph. balcanica, Ph. atra, Ph. procera, Ph.
      ochripes, Ph. diademata and Psylliodes chrysocephalus (Coleoptera, Chrysomelidae,
      Halticinae) were captured than in unbaited control traps. With the exception of
      Ph. cruciferae, this is the first report on significant field attraction by allyl
      isothiocyanate for these species. The species spectrum captured included six
      important agricultural pests. At all sites a great portion of the catch (ranging
      from ca 30 to 98%) was Ph. cruciferae, irrespective of the plant culture. The
      second most abundant species present at most sites was Ph. vittula. The present
      results are very promising from the point of view of applicability of allyl
      isothiocyanate in Europe as a bait in cabbage flea beetle traps for detection and
      monitoring.

PMID- 18069255
TI  - [Epidemiology of multiple myeloma].
AB  - Death rates due to multiple myeloma are increasing by every year in Japan since
      1970. 1,896 men and 1,889 women were died, during 2005. Crude mortality rates are
      also rising since 1970 and reach 3.04 per 100,000 and 2.89 per 100,000 among men
      and women, respectively in 2005. Age-adjusted mortality rates (using the 1985
      Japan Standard) reach 1.5-1.6 per 100,000 in 1995 and persist its value till now.

PMID- 18069256
TI  - [Classification, staging and prognostic indices for multiple myeloma].
AB  - The monoclonal gammopathies are a group of heterogeneous disorders associated
      with monoclonal proliferation of plasma cells. The International Myeloma Working
      Group proposed the new criteria for diagnosis and classification based on
      routinely available examinations. According to the criteria, symptomatic myeloma
      requires evidence of an M -protein in serum and urine, bone marrow plasmacytosis
      and related end -organ damage. The International staging system (ISS) has been
      described to estimate prognosis using serum beta-2 microglobulin and serum
      albumin. The Durie/Salmon plus staging system has also been developed by use of
      PET/MRI imaging. The use of these staging systems will facilitate available
      prognostic factors may allow better definition of prognosis.

PMID- 18069257
TI  - [Diagnosis and management guideline for multiple myeloma].
AB  - The prognosis of patients with multiple myeloma has been improved in the last
      decade due to the induction of autologous stem cell transplantation and novel
      drugs including thalidomide, lenalidomide, and bortezomib into the treatment.
      Recently, the UK Myeloma Forum and International Myeloma Foundation have
      successively proposed myeloma management guidelines. Because many novel drugs are
      not available in Japanese patients, we can not use the same treatment strategy in
      U.S.A. and Europe. In this chapter, the diagnosis and management guideline is
      proposed for Japanese patients with myeloma. For convenience, the recommendations
      are divided into: 1. Diagnostic criteria 2. Indications for starting therapy 3.
      Treatment(initial therapy, maintenance therapy, and therapy for
      refractory/relapsed patients) 4. Response criteria 5. Supportive care and
      management of specific complications.

PMID- 18069258
TI  - [Cytogenetic and molecular basis of multiple myeloma].
AB  - Multiple myeloma(MM) originating from plasma cells is characterized by complex
      chromosomal aberrations. The most prominent chromosomal abnormalities of MM are
      aneuploidy and translocations affecting the immunoglobulin heavy chain locus on
      chromosome 14q32. Additionally, a variety of genetic aberrations such as ras
      mutations have been found in MM. Because these chromosomal and genetic
      abnormalities are closely associated with clinical behavior including prognosis,
      cytogenetic findings have a great impact on planning treatment strategy.
      Furthermore, studies of signal transductions and mechanisms of oncogenesis in
      association with these abnormalities will provide targets to develop novel
      therapeutic agents. Here we summarize the chromosomal and genetic abnormalities
      of MM and their clinical implications.

PMID- 18069259
TI  - [Molecular mechanism of oncogenesis and progression in human myeloma].
AB  - Cellular biology of primary myeloma cells from myeloma patients, has been rapidly
      developing by using DNA analysis, gene expression profiling (GEP) and surface
      marker analysis. These studies reveal that human myeloma cells specifically lose
      the expression of B cell master gene, PAX-5, and express multi-lineage markers,
      and XBP-1 transgenic mice showed the late onset of human myeloma-like monoclonal
      plasmacytosis in the bone marrow of aged mice. GEP reveals that primary myeloma
      cells are subdivided into 7 groups: among these subgroups, PR (proliferation)
      group predicts poor prognosis. With regard to molecular mechanism of myeloma
      oncogenesis, the importance of primary IgH translocation followed by the second
      IgH translocation is proposed, but it is also noted that human myeloma cells show
      the marked heterogeneity.

PMID- 18069260
TI  - [Molecular mechanisms inhibiting proliferation of myeloma cells].
AB  - Accumulating evidences suggest that many molecules are working as inhibitors of
      proliferation in myeloma cells e.g., PTEN, mTOR(PI3-kinase signal molecules),
      p53, RB1, INK4 family and KIP/CIP family (cell cycle check point molecules), PF4
      (inhibitor of angiogenesis). In this review, significance of these molecules in
      myeloma is summarized. Additionally, our finding of growth inhibitory effect by
      PU.1 is explained.

PMID- 18069261
TI  - [Molecular pathogenesis of myeloma for the therapeutic targets].
AB  - Multiple myeloma(MM) is a neoplasia of plasma cells in bone marrow. High dose
      chemotherapy followed by stem cell transplantation and new drugs such as
      thalidomide and bortezomib have improved the survival in MM. However, most of
      patients with myeloma are incurable so there is a need for the new therapeutic
      approaches that have been developed against molecular targets and pathway. It has
      been reported that activation of NF-kappaB pathway was required to survival of
      myeloma cells and this pathway was the potential target for anti -MM therapy.
      Recently we reported diverse genetic aberrations that activated NF-kappaB
      signaling in MM. In this section, the molecular pathogenesis of myeloma,
      especially the new findings related with NF-kappaB activation, will be reviewed
      in Japanese.

PMID- 18069262
TI  - [Experimental animal models of multiple myeloma].
AB  - Human multiple myeloma is an incurable B cell malignancy that accounts for 10% of
      human hematopoietic malignancies and 1% of all human cancers. The characteristic
      features of multiple myeloma are a high production of immunoglobulin, anemia,
      bone lytic lesions, renal impairment. The lack of the ideal animal model of
      multiple myeloma had hampered us to understand its pathology and to develop the
      novel chemotherapy. Recently, the introduction of transgenic technology and the
      immunodeficient mice provided more appropriate model of the human multiple
      myeloma.

PMID- 18069263
TI  - [Clinical features of multiple myeloma].
AB  - The International Myeloma Working Group (IMWG) has recently proposed a new
      classification of asymptomatic myeloma and symptomatic myeloma. The distinction
      between asymptomatic and symptomatic myeloma depends on the presence or absence
      of the myeloma-related organ or tissue impairment (ROTI) defined by the IMWG.
      Based on the definition, some patients without clinical symptoms may fall into
      the "symptomatic" group because of insidious organ impairment by myeloma. Or
      others with clinical symptoms may fall into "asymptomatic" group, if no organ
      impairment is proven to be myeloma related. Recognition of the clinical features
      developed by ROTI is not only important for the diagnosis of symptomatic myeloma
      but also for the immediate institution of effective treatment. Immediate and
      proper management of the clinical features of symptomatic myeloma patients will
      have a great impact on quality of life and survival.

PMID- 18069264
TI  - [Bone lesion in multiple myeloma].
AB  - Bone destruction is a hallmark of multiple myeloma(MM). Almost all MM patients
      develop osteolytic bone lesions that can cause pathologic fractures and severe
      bone pain. Osteolytic lesions result from increased bone resorption due to
      osteoclast stimulation and decreased bone formation due to osteoblast inhibition.
      Plain radiography, CT, and MRI are established imaging techniques in MM. FDG-PET
      imaging is promising newer scanning technique under current evaluation. The
      aggressive features of MM bone lesions have significantly contributed to poor
      prognosis. Therefore, a systemic approach to analgesia, which includes
      radiotherapy and orthopedic intervention, must be applied as a part of the
      comprehensive care plan of MM patient. Bisphosphonates have been shown to reduce
      vertebral fractures and bone pain.

PMID- 18069265
TI  - [Renal disease in multiple myeloma].
AB  - Renal involvement is common in multiple myeloma. Although several types of renal
      disease are observed, most of them are considered to be specifically related to
      monoclonal immunoglobulin light chains. Myeloma cast nephropathy is the most
      frequent and sometimes associated with acute renal failure. AL amyloidosis and
      monoclonal immunoglobulin deposit disease are often presented as a nephrotic
      syndrome. In this review, we describe the pathogenesis and diagnosis of these
      three renal diseases. We also focus on the treatment of renal disease in multiple
      myeloma, in the view points of the chemotherapy to reduce M-protein and the
      prevention to reduce the risks of promoting renal injury.

PMID- 18069266
TI  - [POEMS syndrome: monoclonal plasma cell disorder with polyneuropathy].
AB  - Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS)
      syndrome is a rare multi-organ disease. Because the peripheral neuropathy is
      frequently the overriding symptom and because the characteristics of the
      neuropathy are similar to that chronic inflammatory demyelinating
      polyneuropathy(CIDP), patient are frequently misdiagnosed with CIDP or monoclonal
      gammopathy of undetermined significance (MGUS) -associated peripheral neuropathy.
      Production of vascular endothelial growth factor (VEGF), secreted by
      plasmacytoma, is considered responsible for these symptoms. For isolated
      plasmacytoma, radiotherapy is usually highly effective. Patients without isolated
      plasmacytoma require systemic chemotherapy, which is ineffective in many cases.
      In recent reports, high dose chemotherapy followed by autologous peripheral blood
      stem cell transplantation can dramatically improve clinical manifestations,
      particularly for polyneuropathy in such patients refractory for standard
      chemotherapy.

PMID- 18069267
TI  - [Compromised immune function in multiple myeloma].
AB  - Patients with multiple myeloma are at risk for bacterial infections such as
      Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli.
      Administering oral sulfamethoxazole -trimethoprim for the first 2 months of
      initial chemotherapy was effective prophylaxis for bacterial infection. Specific
      antibody titers for S. pneumoniae were significantly reduced in patients compared
      with normal controls. Pneumococcal vaccination was effective around 30-40% of
      patients. The response rate of influenza vaccination was also limited.
      Intravenous immunoglobulin was useful for prophylaxis of severe bacterial
      infection during plateau-phase of multiple myeloma. The patients who benefit most
      could be identified by measuring IgG antibody responses to pneumococcal
      vaccination.

PMID- 18069268
TI  - [Hypercalcemia in myeloma].
AB  - Hypercalcemia arises in the advanced stage of myeloma due to marked increase in
      osteoclastic bone resorption by local factors in the bone marrow, and is among
      the most serious complications in myeloma. It can progress rapidly and provoke
      acute renal failure and coma, which may become life-threatening. Early detection
      by serum calcium levels and treatment of hypercalcemia is important, although its
      clinical symptoms are difficult to distinguish from those in other underlying
      complications. Bisphosphonates, potent inhibitors of bone resorption, are
      recommended as the most effective therapy and have been approved for treatment of
      hypercalcemia in myeloma.

PMID- 18069269
TI  - [Cytopathological features of multiple myeloma].
AB  - Although integration of laboratory data and radiological findings are required,
      quantity and qualitative evaluation of plasma cells in bone marrow is still
      useful for the diagnosis of multiple myeloma. However, there are considerable
      variations in morphology of myeloma and proliferation pattern among the
      individual patients. Therefore, it is important to recognize cytopathological
      features of myeloma cells for better understanding of patients' status. For
      example, the finding of immature plasmablastic myeloma cells predicts the poor
      prognosis of the patients. In the present review, we described the
      cytopathological features, which is useful for diagnosis and estimation of the
      patients' prognosis and discrimination from reactive non-tumorous plasma cells.

PMID- 18069270
TI  - [Biochemical and immunological findings of multiple myeloma].
AB  - Biochemical and immunological findings of multiple myeloma are reviewed. Rate of
      abnormal data of biochemical markers in monoclonal gammopathy of undetermined
      significance (MGUS), asymptomatic myeloma and symptomatic myeloma are reported.
      Serum albumin, beta2-microglobulin, lactate dehydrogenase, C-reactive protein,
      serum calcium and creatinine are prognostic factors. Free light chain (FLC) assay
      is useful for monitoring of intact immunoglobulin myeloma as well as nonsecretory
      and light chain only myeloma. In MGUS, serum FLC ratio is an independent risk
      factor for progression. Phenotypic analysis of plasma cells is useful for
      differential diagnosis and understanding of proliferative state in multiple
      myeloma.

PMID- 18069271
TI  - [Imaging techniques in multiple myeloma].
AB  - Multiple myeloma is an incurable malignancy characterized by the accumulation of
      neoplastic plasma cells in the bone marrow and osteolytic bone destruction. The
      imaging techniques play an essential role in the assessment of skeletal
      involvement, the detection of extramedullary diseases, and the characterization
      of organ complications. Plain X-rays are routinely used for skeletal surveys;
      however, the sensitivity is not sufficient to detect early osteolytic lesions.
      New imaging techniques such as multislice computed tomography (CT), magnetic
      resonance imaging (MRI), and whole body positron emission tomography (PET) offer
      advanced diagnostic accuracy. These imaging modalities allow for more precise
      staging and contribute to further improvement in the management of this disease.

PMID- 18069272
TI  - [How to diagnose a patient precisely as a myeloma patient?--Lots of problems
      during diagnostic process].
AB  - Typical multiple myeloma can be diagnosed precisely through lots of evaluations
      including the confirmation of the presence of increased clonal myeloma cells in
      bone marrow accompanied by monoclonal protein, cytopenia, bone diseases and renal
      disturbance. However, there still exists not a little difficulity during
      diagnostic process. In this article, representative problems are presented. Among
      them, the following issues are included; the confirmation or identification of
      minimal or 'masked' monoclonal proteins in several conditions (eg. myeloma
      following polyclonal hypergammaglobulinemic conditions), the differential
      diagnosis between Waldenstrom macroglobulinemia and IgM multiple myeloma, the
      differential diagnosis between MGUS with various complications and myeloma, the
      differential diagnosis of tumors in refractory phase of myeloma (eg.
      extramedullary plasmacytoma or transition to lympho -proliferative disorders from
      myeloma), and finally the interpretation of new M-component or oligo-clonal
      protein band in some periods after stem cell transplantation for myeloma.

PMID- 18069273
TI  - [Chemotherapy for multiple myeloma].
AB  - The combination of the melphalan and prednisolone (MP) can induce objective
      responses in about 50% of patients with multiple myeloma (MM) since its
      introduction in 1960. Since then many combination chemotherapy regimens have been
      used, but a large metaanalysis showed that the combination of oral MP is as
      effective as combination regimens including intravenous drugs. In recent years,
      many novel agents (including bortezomib, thalidomide, and liposomal doxorubicin)
      have been developed for the MM treatment. More recently, MP has been used in
      combination with these novel agents. The combination treatment of MP and
      thalidomide, overall survival was significantly better than seen in the MP
      treatment. In the near future, primary induction therapy will be changed.

PMID- 18069274
TI  - [Role of interferon for the treatment of myeloma].
AB  - Interferon (IFN)-alpha inhibits the growth of myeloma cell lines by inducing
      apoptosis. Based upon this finding, IFN has been evaluated in clinical trials as
      single-agent induction therapy, induction in combination with chemotherapy, and
      as maintenance therapy in plateau phase. Available data suggest that progression
      free survival is improved with IFN, but the survival benefit is small. IFN has
      also been evaluated as maintenance after high-dose chemotherapy; however, the
      true benefit of IFN maintenance remains to be elucidated in view of conflicting
      data. In an area of rapidly increasing treatment options, novel agents, which
      have less toxicity and more biologic rationale, outweigh the limited benefits for
      IFN.

PMID- 18069275
TI  - [Action mechanism of thalidomide in treatment of multiple myeloma].
AB  - Thalidomide, N-phtalidoglutamide, is a well-known teratogenic agent when given to
      pregnant women. It was first synthesized by CIBA in 1953, but put on market in
      Germany as a sedative, but Dr. Rentz reported first the relation with the
      teratogenicity. However, its clinical activity to erythema nodosum leprosum was
      accidentally found. In 1997, thalidomide was found active to multiple myeloma,
      but its clinical use is not authorized yet in Japan. The mechanisms which so far
      reported are as follows. 1) The inhibitory activity of angiogenesis 2) NF-kappaB
      suppression 3) Suppression of GVHD, and other activity to immunity (suppression
      or augmentation), suppression of TNFa 4) Suppression of intracellular adhesion
      molecule 5) Binding to DNA From these reports, the teratogenicity or the clinical
      activities have been somewhat understood. Recently clinical studies of the
      analogue, Lenalidomide, have been reported.

PMID- 18069276
TI  - [Application and safety of thalidomide in the treatment of multiple myeloma].
AB  - Thalidomide is now regarded as one of the most promising salvage therapies for
      refractory or relapsed multiple myeloma. Appropriate use of this drug is
      indispensable to avoid repeating drug-induced disaster. Recently, its application
      has been expanded from refractory or relapsed cases also to untreated patients or
      post transplanted cases. Thus, it should be clarified which population of the
      Japanese patients with myeloma may truly benefit by this drug. Guideline,
      recently established by the Japanese Society of Clinical Hematology, has
      functioned for safety use of this drug. For future approval by Japanese
      government, strict but well-organized system for safety applicable to the
      clinical setting in Japan is necessary.

PMID- 18069277
TI  - [Development of thalidomide analogs for the treatment of multiple myeloma (MM)].
AB  - After the introduction of thalidomide (Thal) in the treatment of MM in 90's,
      several thalidomide analogs have been developed. Among them, CC-5013
      (lenalidomide: Lenal) is the most potent and promising novel oral agent. Compared
      with Thal, Lenal is 50 to 2,000 times more potent at stimulating T cell
      proliferation and 50 to 100 times more potent at augumenting several cytokines. A
      phase I trial established a maximal tolerated oral dose for Lenal of 25 mg daily.
      Phase II study showed significant anti-MM activity of Lenal with less or no
      reports of significant somnolence, constipation, or neuropathy as with Thal
      therapy. Based on these findings, several phase III studies are on going
      internationally.

PMID- 18069278
TI  - [Role of bortezomib in the treatment of multiple myeloma].
AB  - The proteasome inhibitor bortezomib is approved for the treatment of patients
      with relapsed/refractory multiple myeloma. Botezomib represents a new generation
      of treatments for multiple myeloma that affects both specific intracellular
      signaling pathways and the tumor microenvironment. There is a growing body of
      clinical evidence showing its effectiveness alone and in combination not only in
      relapsed/refractory cases but also in the front line setting. Regimens
      incorporating bortezomib and other novel agents such as immunomodulatory
      derivatives of thalidomide together with commonly used conventional drugs show
      considerable high response rates including complete response that resulting in
      improving survival, with or without following stem cell transplantation. Thus
      these approaches represent a promising future direction in myeloma treatment.

PMID- 18069279
TI  - [Bisphosphonates for myeloma patients].
AB  - Several species of bisphosphonate (BP) have been widely used as one of the
      standardized supportive therapy for myeloma patients, because of the efficacy
      evidenced by lots of prospective randomised trials showing the decreased
      incidence of the skeletal-related events. In addition, BPs have lots of
      beneficial effects on myeloma patients, including the enhancement of lymphocyte
      subset, and anti-myeloma effects possibly by 'indirect' effects on myeloma cells
      via apoptosis-inducing effects on osteoclasts, as well as 'direct' apoptosis 
      inducing effects on myeloma cells. On the contrary, BPs have been shown to have
      adverse events, including transient flu -like syndrome accompanied by fever and
      transient inflammatory reactions, and unexpected severe tissue damage, named
      'osteonecrosis of the jaw (ONJ)'. Once ONJ developed in myeloma patients, myeloma
      therapies could be influenced drastically at times, because ONJ site could become
      infection focus and necessitate cessation of cytotoxic therapy in order to
      support tissue repair in situ. Prevention of ONJ might be feasible through oral
      hygiene, because ONJ develops almost always in patients with long-history of
      dental diseases.

PMID- 18069280
TI  - [Role of stem cell transplantation in treatment of multiple myeloma].
AB  - The role of stem cell transplantation in the treatment of multiple myeloma (MM)
      is described. High-dose chemotherapy (HDT) followed by autologous stem cell
      transplantation (SCT) is routinely recommended for most patients with newly
      diagnosed MM under 65 years of age. However, recently published meta-analysis of
      randomized controlled trials indicated PFS benefit but not OS benefit for HDT
      with autologous SCT performed early in MM. Tandem autologous SCT is superior to
      single transplantation in terms of event-free survival. Survival in recipients of
      autologous SCT followed by reduced-intensity conditioning allogeneic
      transplantation is superior to that in recipients of tandem autologous SCT.
      Recently developed new drugs including thalidomide, lenalidomide or bortezomib in
      combination with SCT might improve survival of myeloma patients.

PMID- 18069281
TI  - [Molecular targeting therapy for multiple myeloma].
AB  - Molecular target therapy is the most progressive and promising anticancer therapy
      in last decade. Multiple myeloma is also one of the major therapeutic targets for
      using molecular based technology. The recent availability of clinical data
      regarding thalidomide-, lenalidomide-, and bortezomib-based regimens has provided
      new, effective treatment options for patients with both newly diagnosed and
      relapsed/refractory multiple myeloma. We are expecting that future clinical
      trials can be designed to achieve a high likelihood of success based on molecular
      studies, cell-signaling, and correlative science studies. Studies with these
      agents also provide new insight into the cancer biology underlying multiple
      myeloma in humans.

PMID- 18069282
TI  - [Prognositic factors in multiple myeloma].
AB  - The article about the prognostic factors in multiple myeloma is reviewed. PS,
      albumin, sex, LDH, myeloma % in bone marrow, beta2MG, kappa > lambda, IgG>nonIgG,
      the serum concentration of IgG M protein, Hb, WBC, platelet, creatinine, calcium
      and CRP were reported as siginificant factors using univariate analysis in
      Japanese patients with myeloma. According to the result of multivariate analysis,
      two factors of albumin and beta2 MG have been adopted in the International
      Staging System in multiple myeloma (ISS). We can use the prognostic factor as a
      clue to the estimation of the clinical status and the prognosis in each case.

PMID- 18069283
TI  - [Situation of translational research and development of molecular-targeted agents
      for multiple myeloma].
AB  - The most important point of the translational research for oncology is clinical
      application. The excellent research will clarify the molecular pathogenesis of
      cancer and develop a beneficial intervention in the clinic. The laboratory
      science done on patient material is a critical part of the translational
      research. However, there are several problems to expand the translational
      research in Japan. Developing excellent basic researches and arranging systems to
      support the translational research will be necessary.

PMID- 18069284
TI  - [Practical strategies against bioterrorism].
AB  - Bioterrorism is terrorism by intentional release of viruses, bacteria, toxins or
      other agents to cause illness or death in people. Especially, anthrax, smallpox,
      plague, botulism, tularemia, and viral hemorrhagic fevers are important illness
      due to biological agents with a high potential for adverse public health impact.
      These biological agents can be spread through the air, through water, or in food
      and may cause disasters in the society. Furthermore, difficulties in detection
      and identification of the bioterrorism agents may result in immense harm. Then we
      need to take actions for the preparation for unexpected events to keep the damage
      to a minimum.

PMID- 18069285
TI  - [Proton pump inhibitor in the management of acid-related disorders in Japan:
      history and perspective].
AB  - Since the introduction of proton pump inhibitors(PPI) in Japan, their role in the
      management of acid-related diseases (ARD) is steadily increasing based on their
      effectiveness, safety profile and lifting of cumbersome regulation in their
      prescription. However, further efforts to get the approval of re-imbursement for
      two major problems in Japan, prevention of nonsteroidal anti-inflammatory drug
      (NSAID)-induced ulcers and eradication therapy for chronic gastritis caused by
      Helicobacter pylori (HP), should be made. Continuous efforts to increase the
      awareness to evidence-based medicine (EBM) that leads to behavioral changes
      should be continued, for which guidelines will be instrumental. The Japanese
      Society of Gastroenterology (JSGE) has started to formulate six guidelines among
      which gastroesophageal reflux disease (GERD) and peptic ulcer disease are
      included. Thus, standard management policies for ARD are expected to be published
      in the near future and will be continuously improved and contribute to the better
      patient care in Japan. In the next decades, we should promote our activity to
      produce solid new evidence for better management of ARD from Japan to the world.

PMID- 18069286
TI  - [Attention-getting infectious diseases: Importance of renewed awareness].

PMID- 18069287
TI  - [World condition of avian influenza].

PMID- 18069288
TI  - [Countermeasures for newly-emerging influenza].

PMID- 18069289
TI  - [Attention-getting zoonoses: Rabies].

PMID- 18069290
TI  - [Attention-getting zoonoses: Q fever].

PMID- 18069291
TI  - [Attention-getting zoonoses: Cryptosporidiosis].

PMID- 18069292
TI  - [Attention-getting zoonoses: Hepatitis E].

PMID- 18069293
TI  - [Attention-getting zoonoses: Variant CJD].

PMID- 18069294
TI  - [Mosquito-vector infections: Dengue fever].

PMID- 18069295
TI  - [Mosquito-vector infections: West Nile fever].

PMID- 18069296
TI  - [Attention-getting sexually transmitted diseases: HIV-1 infection].

PMID- 18069297
TI  - [Attention-getting sexually transmitted diseases: Hepatitis B].

PMID- 18069298
TI  - [Attention-getting sexually transmitted diseases: Human papillomavirus
      infections].

PMID- 18069299
TI  - [Attention-getting cross infections: Multidrug resistant Pseudomonas aeruginosa
      infections].

PMID- 18069300
TI  - [Attention-getting cross infections: Extended-spectrum beta-lactamase-producing
      bacterial infections].

PMID- 18069301
TI  - [Attention-getting cross infections: Viral enteritis].

PMID- 18069302
TI  - [Diagnosis and therapy for attention-getting infections (discussion)].

PMID- 18069303
TI  - [Long- term remission survival with a case of rectal carcinoid tumor with
      metastasis in the soft tissue effectively treated with the combination therapy of
      irinotecan/5-fluorouracil/levofolinate followed by resection].

PMID- 18069304
TI  - [Severe arrythmic events triggered by fever in a case of Brugada syndrome].

PMID- 18069305
TI  - [Hypersensitivity pneumonitis caused by the use of goose feather coverlet].

PMID- 18069306
TI  - [Anti-signal recognition particle (SRP) antibody positive polymyositis refractory
      to corticosteroid treatment].

PMID- 18069307
TI  - [Sclerosing cholangitis with autoimmune pancreatitis which resembles
      cholangiocarcinoma].

PMID- 18069308
TI  - [Marked effectiveness of cilostazol in a case of hemodynamic TIA].

PMID- 18069309
TI  - [Reversible posterior leukoencephalopathy syndrome with microscopic
      polyangiitis].

PMID- 18069310
TI  - [Mitochondrial encephalomyopathy with elderly onset of psychiatric disorder].

PMID- 18069311
TI  - [Diagnostic criteria for primary aldosteronism].

PMID- 18069312
TI  - [Heart rehabilitation in developed countries: Exercise therapy].

PMID- 18069313
TI  - [Guidelines in diagnosis and therapy for acute-phase ischemic cerebrovascular
      disorders: Intravenous rt-PA therapy].

PMID- 18069315
TI  - [Diagnosis procedure combination].

PMID- 18069314
TI  - [Study on sleep apnea syndrome from view of various fields of medicine].

PMID- 18069316
TI  - [Management and communication in health care].

PMID- 18069317
TI  - [Osmoadaptation of haloalkaliphilic bacteria: role of osmoregulators and their
      possible practical application].
AB  - The review discusses osmoadaptation of haloalkaliphilic bacteria from diverse
      taxonomic and physiological groups, inhabiting soda lakes. Our experimental
      research has confirmed the similarity of the osmoregulation strategies in
      neutrophilic and alkaliphilic halophiles, independent of their pH homeostasis
      mechanism. The external osmotic pressure is equilibrated either due to
      accumulation of ions from the environment, or by accumulation or synthesis of
      cytoplasmic osmoregulatory compounds. The alkaliphiles following the "compatible
      solutes" strategy contain low or moderate concentrations of salts in their
      cytoplasm; their proteins do not require adaptation to salts. Those that follow
      the "salt-in" strategy do not synthesize osmoregulators: they accumulate high
      levels of salts within the cell and thus equilibrate the osmotic pressures of the
      cell and the environment. The proteins of these bacteria contain more acidic
      amino acid residues compared to the proteins of neutrophiles. The functions of
      bacterial organic osmoregulatory compounds are discussed, as well as their
      characteristics of possible practical value. Applications for ectoine and betaine
      are discussed based on the published data.

PMID- 18069318
TI  - [Radioisotopic assays of rates of carbon monoxide conversion by anaerobic
      thermophilic prokaryotes].
AB  - The rate of CO conversion by a pure culture of a thermophilic CO-oxidizing, H2
      producing bacterium Carboxydocella sp. strain 1503 was determined by the
      radioisotopic method. The overall daily uptake of 14CO by the bacterium was
      estimated at 38-56 micromol CO per 1 ml of the culture. A radioisotopic method
      was developed to separate and quantitatively determine the products of anaerobic
      CO conversion by microbial communities in hot springs. The new method was first
      tested on the microbial community from a sample obtained from a hot spring in
      Kamchatka. The potential rate of CO conversion by the anaerobic microbial
      community was found to be 40.75 nmol CO/cm3 sediment per day. 85% of the utilized
      14CO was oxidized to carbon dioxide; 14.5% was incorporated into dissolved
      organic matter, including 0.2% that went into volatile fatty acids; 0.5% was used
      for cell bio mass production; and only just over 0.001% was converted to methane.

PMID- 18069319
TI  - [Reduction of chromate, selenite, tellurite, and iron(III) by the moderately
      thermophilic bacterium Bacillus thermoamylovorans SKC1].
AB  - A moderately thermophilic, facultatively anaerobic bacterium capable of reducing
      Cr(VI) (strain SKC1) was isolated from municipal sewage. Based on the analysis of
      the 16S rRNA gene nucleotide sequence and DNA-DNA hybridization data, strain SKC1
      was identified as a representative of the species Bacillus thermoamylovorans. B.
      thermoamylovorans SKC1 is capable of reducing chromate with L-arabinose as an
      electron donor with an optimum at 50 degrees C and neutral pH. The culture is
      able to reduce Cr(VI) at its initial concentration in the medium of up to 150
      mg/l. In addition to chromate, strain SKC1 is capable of reducing selenite and
      tellurite, as well as soluble forms of Fe(III). It was shown that Cr(VI), Te(IV),
      and Se(IV) exert a bacteriostatic effect on strain SKC1, and the reduction of
      these anions performs the detoxification function. This is the first
      communication on the reduction of chromate, selenite, tellurite, and soluble
      Fe(III) species by a culture of thermophilic bacilli.

PMID- 18069320
TI  - [Fatty acid composition of Wautersia eutropha lipids under conditions of active
      polyhydroxyalkanoates synthesis].
AB  - The fatty acid composition of the lipids of a Wautersia eutropha
      polyhydroxyalkanoate-producing strain was studied by chromato-mass spectrometry.
      A total of 27 fatty acids were identified; their distribution in the cell
      fractions was determined. In the cytoplasmic membrane, palmitic, palmitoleic, and
      cis-vaccenic acids were the major components. Long-chain beta-hydroxy acids and
      myristic acid (components of the lipopolysaccharides of the cell envelope)
      predominated in the fraction of strongly bound lipids. When the polymer was
      actively synthesized, the content of cyclopropane acids in the easily extracted
      lipids increased and the content of the corresponding monoenoic acids decreased.
      The strongly bound lipids had a high content of long-chain beta-hydroxy acids
      (more than 50% of the total fatty acids). These results made it possible to
      determine the source of polyhydroxyalkanoate (PHA) contamination and to choose
      the strategy for their purification.

PMID- 18069321
TI  - [Comparative study of the fatty acid composition of some groups of purple
      nonsulfur bacteria].
AB  - The fatty acid composition (FAC) of 43 strains of purple nonsulfur bacteria
      belonging to six genera--Rubrivivax, Rhodopseudomonas, Rhodoplanes,
      Blastochloris, Rhodobium, and Rhodomicrobium--was studied by capillary gas
      chromatography. The cultures were grown on standard medium under standard
      conditions. Automatic identification of the fatty acid methyl esters and
      statistical processing of the results were performed by the computerized
      Microbial Identification System (M.I.S). Significant differences between the FACs
      of different genera, species, and, sometimes, strains were revealed. 16S rRNA
      genes of some of the new isolates, primarily those having a specific FAC, were
      sequenced. The taxonomic status of a number of the strains in question was
      determined using the FAC characteristics as one of the criteria. It was shown
      that the FAC characteristics may be used both for affiliating the isolates to
      known species and for revealing new taxa.

PMID- 18069322
TI  - [Biochemical aspects of basidiospore maturation in Agaricus bisporus at various
      temperatures].
AB  - Phosphatidylethanolamine is the main phospholipid of Agaricus bisporus
      basidiospores obtained under sterile conditions from young basidiomes with closed
      partial veils. Storing the basidiospores for five months at room temperature
      resulted in a complete loss of their germinating capacity. Conversely, storing
      them at a low temperature increased their germination rate by 15-20%. At both
      temperature levels, the phosphatidylcholine ratio significantly increased during
      storage to the level found in mature basidiospores. In addition, a drastic (8-10
      fold) decrease in trehalose content occurred after two months of storage at room
      temperature. The trehalose content decreased only 1.5-fold at low temperatures.
      The involvement of trehalose and lipids in the retention of spore viability is
      discussed.

PMID- 18069323
TI  - [The composition of the chitinolytic microbial complex and its effect on chitin
      decomposition at various humidity levels].
AB  - The dynamics of assimilation of chitin by soil microorganisms (primarily
      prokaryotes) as a source of carbon and nitrogen has been determined by gas
      chromatography and fluorescence microscopy. The highest rates of chitin
      decomposition in chernozem were detected at humidity levels corresponding to the
      pressure of soil moisture (P) of -1.4 atm. The rate of microbial consumption of
      chitin is three times higher than that of the carbon of soil organic matter.
      Fluorescence microscopy revealed that an increase in the pressure of soil
      moisture from P = -10 atm to P = -0.7 atm resulted in a considerable increase in
      the proportion of the specific surface of mycelial bacteria (actinomycetes).

PMID- 18069324
TI  - [The effect of Spo0A and AbrB proteins on expression of the genes of guanyl
      specific ribonucleases from Bacillus intermedius and Bacillus pumilus in Bacillus
      subtilis recombinant strains].
AB  - Guanyl-specific ribonucleases from Bacillus intermedius and Bacillus pumilus are
      actively secreted under phosphate starvation by recombinant strains of Bacillus
      subtilis with native regulatory systems and by strains defective in some proteins
      of the Spo0A phosphorylation pathway. The level of expression of ribonuclease
      genes has been shown to increase approximately sixfold in recombinant strains
      with mutation in the spo0A gene and threefold in the spo0A/abrB mutants, as
      compared with native strains. These results demonstrate that the Spo0A protein
      regulates the production of ribonucleases and thus acts as a repressor, while the
      AbrB protein is an activator of expression of the genes encoding ribonucleases
      from Bacillus intermedius and Bacillus pumilus in Bacillus subtilis cells.

PMID- 18069325
TI  - [Heterologous expression of Bacillus intermedius gene of glutamyl endopeptidase
      in Bacillus subtilis strains defective in regulatory proteins].
AB  - Expression of the gene of glutamyl endopeptidase from Bacillus intermedius
      (gseBi) cloned on the plasmid pV has been studied in Bacillus subtilis
      recombinant strains with mutations of the regulatory proteins involved in
      sporogenesis and spore germination. It has been established that inactivation of
      the regulatory protein Spo0A involved in sporulation initiation resulted in a
      decrease in the expression of the gseBi gene by 65% on average. A mutation in the
      gene of the sensor histidine kinase kinA had no effect on the biosynthesis of the
      enzyme. Inactivation of Ger proteins regulating bacterial spore germination
      resulted in a 1.5-5-fold decrease in glutamyl endopeptidase activity. It has been
      concluded that expression of the B. intermedius glutamyl endopeptidase gene from
      plasmid pV in recombinant cells of B. subtilis is under impaired control by the
      regulatory system of Spo0F/Spo0A phosphorelay, which participates in sporulation
      initiation. The regulatory Ger proteins responsible for spore germination also
      affect expression of the gene of this enzyme.

PMID- 18069326
TI  - [Ultrastructural organization and development cycle of soil ultramicrobacteria
      belonging to the class Alphaproteobacteria].
AB  - Gram-negative chemoorganotrophic soil ultramicrobacteria (UMB), strains NF1 and
      NF3, have been isolated. In their development cycle, the strains formed small
      coccoid cells of 400-800 nm and ultrasmall cells of 200-300 nm. Phylogenetically,
      the strains NF1 and NF3 belong to Alphaproteobacteria and are close to the type
      strain of the recently described species Kaistia adipata. The ultrastructure of
      UMB cells has been studied using ultrathin sections and freeze-fracturing. It has
      been shown that the structure of UMB cell walls is of the gram-negative type; the
      outer membrane and peptidoglycan layer are well differentiated. The cell surface
      has numerous protrusions (prosthecae) of conical or spherical shape filled with
      the contents of the periplasm. The formation of unusual cellular structures (not
      occurring in known free-living bacteria) is a feature of UMB: these include the
      following: (a) piles of rod-like subunits, ca. 30 A in diameter and 150-250
      angstroms in length: (b) long bunches (up to 300-400 angstroms) comprised of
      filamentous subunits; and (c) large electron-dense spherical bodies (up to 200
      300 angstroms in diameter) localized in the periplasm. A distinctive feature of
      UMB is their ability to grow as facultative parasites on living cyanobacterial
      (CB) cells. In this case, three types of interaction between UMB and CB have been
      revealed: (1) adsorption of UMB cells on the surface of CB cells; (2) penetration
      of UMB into polysaccharide sheathes; and (3) penetration of UMB into CB
      eytoplasm. UMB cells have been shown to reproduce by budding, with buds (up to 2
      3) located directly on the mother cell, without formation of intennediate hyphae.

PMID- 18069327
TI  - [Application of the complex of DNA with the congo red anionic diazo dye for
      detection of nuclease-producing colonies of marine bacteria].
AB  - This study was aimed at the development of a method for detection of colonies of
      nuclease-secreting marine bacteria. The BAL nuclease-producing marine bacterium
      Pseudoalteromonas espejiana BAL-31 was used as the test object. A new method was
      developed involving the congo red (CR) anionic dye. The P. espejiana culture was
      plated on nutrient agar with CR and denatured DNA. In such media. CR was found to
      form complexes with DNA. After two days of incubation at 30 degrees C, halos were
      found around the P. espejiana colonies. No halos appeared when DNA was not
      introduced, when BAL nuclease was inactivated, or when the medium was inoculated
      with Escherichia coli. It was concluded that the halos around the colonies
      indicated nuclease excretion. The halos were shown to result from the coagulation
      of CR released after digestion of the CR-DNA complex by the nuclease. This method
      for detection of nuclease-producing colonies can probably be used for all marine
      bacteria and possibly for halophilic bacteria as well.

PMID- 18069328
TI  - [Seasonal dynamic of the numbers of epiphytic yeasts].
AB  - The numbers of epiphytic yeasts on the leaves and flowers of 25 plant species
      throughout their vegetation period was determined. The numbers of yeasts on the
      leaves were found to change regularly throughout the year. The average dynamics
      for all of the plant species investigated included an increase in yeast numbers
      during spring and summer with the maximum in late autumn and early winter. The
      character of the yeasts' dynamics depends on the ecological characteristics of
      the plants and the duration of the ontogenesis of their leaves and flowers. Three
      types of dynamics of epiphytic yeasts were revealed: year-round with an increase
      in autumn-winter, year-round without visible changes, and seasonal with a
      terminal increase for annual plants.

PMID- 18069329
TI  - [Development and relations of Fusarium culmorum and Pseudomonas fluorescens in
      soil].
AB  - The development of Fusarium culmorum and Pseudomonas fluorescens in soil, and the
      relations between them, were studied using membrane filters containing the
      fungus, the bacterium, or both microorganisms; the filters were incubated in
      soil. F. culmorum was identified by indirect immunofluorescence: the GUS-labeled
      strain was used to visualize P. fluorescens. It was found that F. culmorum
      introduced in soil can develop as a saprotroph, with the formation of mycelium,
      macroconidia, and a small amount of chlamydospores. Introduction of glucose and
      cellulose resulted in increased density of the F. culmorum mycelium and
      macroconidia. P. fluorescens suppressed development of F. culmorum mycelium in
      soil but stimulated formation of fungal chlamydospores. Decreased mycelial
      density in the presence of P. fluorescens was more pronounced in unsupplemented
      soil and less pronounced when glucose or cellulose was intiodaced. F. culmorum
      had no significant effect on P. fluorescens growth in soil.

PMID- 18069330
TI  - [Microbial processes of the carbon and sulfur cycles in the Chukchi Sea].
AB  - The research performed in August 2004 within the framework of the Russian
      American Long-term Census of the Arctic (RUSALCA) resulted in the first data
      concerning the rates of the key microbial processes in the water column and
      bottom sediments of the Bering strait and the Chukchi Sea. The total bacterial
      counts in the water column varied from 30 x 10(3) cells ml(-1) in the northern
      and eastern parts to 245 x 10(3) cells ml(-1) in the southern part. The methane
      content in the water column of the Chukchi sea varied from 8 nmol CH4 l(-1) in
      the eastern part of the sea to 31 nmol CH4 l(-1) in the northern part of the
      Herald Canyon. Active microbial processes occurred in the upper 0-3 cm of the
      bottom sediments; the methane formation rate varied from 0.25 to 16 nmol CH4 dm(
      3) day(-1). The rates of methane oxidation varied from 1.61 to 14.7 nmol CH4 dm(
      3) day(-1). The rates of sulfate reduction varied from 1.35 to 16.2 micromol
      SO4(2-) dm(-3) day(-1). The rate of methane formation in the sediments increased
      with depth, while sulfate reduction rates decreased (less than 1 micromol SO4(2-)
      dm(-3) day(-1)). These high concentrations of biogenic elements and high rates of
      microbial processes in the upper sediment layers suggest a specific type of
      trophic chain in the Chukchi Sea. The approximate calculated balance of methane
      emission from the water column into the atmosphere is from 5.4 to 57.3 micromol
      CH4 m(-2) day(-1).

PMID- 18069331
TI  - [Microbiological analysis of cryopegs from the Varandei Peninsula, Barents Sea].
AB  - The paper deals with the microbiological characterization of water-saturated
      horizons in permafrost soils (cryopegs) found on the Varandei Peninsula (Barents
      Sea coast), 4-20 m deep. The total quantity of bacteria in the water of cryopegs
      was 3.5 x 10(8) cells/ml. The population of cultivated aerobic heterotrophic
      bacteria was 3-4 x 10(7) cells/ml and the number of anaerobic heterotrophic
      bacteria varied from 10(2) to 10(5) cells/ml depending on cultivation temperature
      and salinity. Sulfate-reducing bacteria and methanogenic archaea were found as
      hundreds and tens of cells per ml of water, respectively. A pure culture of a
      sulfate-reducing strain B15 was isolated from borehole 21 and characterized.
      Phylogenetic analysis has shown that the new bacterium is a member of the genus
      Desulfovibrio with Desulfovibrio mexicanus as its closest relative (96.5%
      similarity). However, the significant phenotypic differences suggest that strain
      B15 is a new species of sulfate-reducing bacteria.

PMID- 18069332
TI  - [Analysis of the bacterial community developing in the course of Sphagnum moss
      decomposition].
AB  - Slow degradation of organic matter in acidic Sphagnum peat bogs suggests a
      limited activity of organotrophic microorganisms. Monitoring of the Sphagnum
      debris decomposition in a laboratory simulation experiment showed that this
      process was accompanied by a shift in the water color to brownish due to
      accumulation of humic substances and by the development of a specific bacterial
      community with a density of 2.4 x 10(7) cells ml(-1). About half of these
      organisms are metabolically active and detectable with rRNA-specific
      oligonucleotide probes. Molecular identification of the components of this
      microbial community showed the numerical dominance of bacteria affiliated with
      the phyla Alphaproteobacteria, Actinobacteria, and Phanctomycetes. The population
      sizes of Firmicutes and Bacteroidetes, which are believed to be the main agents
      of bacterially-mediated decomposition in eutrophic wetlands, were low. The
      numbers of planctomycetes increased at the final stage of Sphagnum decomposition.
      The representative isolates of Alphaproteobacteria were able to utilize
      galacturonic acid, the only low-molecular-weight organic compound detected in the
      water samples; the representatives of Planctomycetes were able to decompose some
      heteropolysaccharides, which points to the possible functional role of these
      groups of microorganisms in the community under study. Thus, the composition of
      the bacterial community responsible for Sphagnum decomposition in acidic and low
      mineral oligotrophic conditions seems to be fundamentally different from that of
      the bacterial community which decomposes plant debris in eutrophic ecosystems at
      neutral pH.

PMID- 18069333
TI  - [Abundance, biomass, structure, and activity of the microbial complexes of
      minerotrophic and ombrotrophic peatlands].
AB  - Very large microbial biomass was revealed in peat bogs by means of fluorescence
      microscopy. In ombrotrophic peatlands, the pool of the dry-weight microbial
      biomass in the 1.5-m layer constituted 3-4 t/ha and was twice as high as in the
      minerotrophic peat bogs. Fungal biomass was predominant (55-99%) in ombrotrophic
      peatlands, while bacterial biomass predominated in minerotrophic peatlands (55
      86%). In ombrotrophic peatlands, the microbial biomass was concentrated in the
      upper layers, while in minerotrophic peatlands, it was uniformly distributed in
      the bulk. After drainage, the microbial pool in the ombrotrophic peatlands
      increased twofold; that in the minerotrophic peatlands remained at the same
      level. The potential activity of nitrogen fixation and denitrification was
      revealed across the whole profile of the peatlands. The average values of these
      potential activities were five times higher in the minerotrophic peatlands, where
      bacterial biomass predominated.

PMID- 18069334
TI  - ["Do not lose the winning games". To the 100th anniversary of M.E. Lobashev].
AB  - Mikhail E. Lobashev (1907-1971), Head of the Department of Genetics and Breeding
      with the Leningrad (now, St. Petersburg) State University from 1957 to 1971, had
      traveled a long way from a homeless to an Honored Scientist of the Russian
      Federation. Lobashev was among the discoverers of chemical mutagenesis in
      Drosophila; he pioneered in connecting the mutation process and the repair of
      genetic material and developed the concept of signal inheritance. Through the
      entire Great Patriotic War, he served with the field forces, and defended his
      doctoral dissertation on the physiological hypothesis of mutation process in 1946
      on the return to the University. In 1948, Mikhail Efimovich was discharged from
      the University, where he was the Dean of the Biological Faculty, as a Morganist.
      On his return to the University in 1957, Lobashev devoted all his energies to the
      restoration of genetic education in this country, wrote the first domestic
      genetic textbook in the post-Lysenko period, organized the research at the
      Department of Genetics and Breeding, and created the scientific school, whose
      representatives are still successfully working in the field of genetics.

PMID- 18069335
TI  - [Stress, chemocommunication, and the physiological hypothesis of mutation].
AB  - The review considers stress as a physiological state of the organism, affecting
      the cellular, genomic, and population levels. Literature data and cytogenetic
      studies by the author support basic statements of the physiological hypothesis of
      mutation, which was advanced as early as in the 1940s. Studies of pheromonal
      effects in germline and somatic cells of the house mouse demonstrated the role of
      olfactory stressors in generating genetic variation in microevolutionary changes.

PMID- 18069336
TI  - [Vertebrate immunity: mutator proteins and their evolution].
AB  - M.E. Lobashev has brilliantly postulated in 1947 that error-prone repair
      contribute to mutations in cells. This was shown to be true once the mechanisms
      of UV mutagenesis in Escherichia coli were deciphered. Induced mutations are
      generated during error-prone SOS DNA repair with the involvement of inaccurate
      DNA polymerases belonging to the Y family. Currently, several distinct mutator
      enzymes participating in spontaneous and induced mutagenesis have been
      identified. Upon induction of these proteins, mutation rates increase by several
      orders of magnitude. These proteins regulate the mutation rates in evolution and
      in ontogeny during immune response. In jawed vertebrates, somatic
      hypermutagenesis occurs in the variable regions of immunoglobulin genes, leading
      to affinity maturation of antibodies. The process is initiated by cytidine
      deamination in DNA to uracil by AID (Activation-Induced Deaminase). Further
      repair of uracil-containing DNA through proteins that include the Y family DNA
      polymerases causes mutations, induce gene conversion, and class switch
      recombination. In jawless vertebrates, the variable lymphocyte receptors (VLR)
      serve as the primary molecules for adaptive immunity. Generation of mature VLRs
      most likely depends on agnathan AID-like deaminases. AID and its orthologs in
      lamprey (PmCDA1 and PMCDA2) belong to the AID/APOBEC family of RNA/DNA editing
      cytidine deaminases. This family includes enzymes with different functions:
      APOBEC1 edits RNA, APOBEC3 restricts retroviruses. The functions of APOBEC2 and
      APOBEC4 have not been yet determined. Here, we report a new member of the
      AID/APOBEC family, APOBEC5, in the bacterium Xanthomonas oryzae. The widespread
      presence of RNA/DNA editing deaminases suggests that they are an ancient means of
      generating genetic diversity.

PMID- 18069337
TI  - [Consequences of selection in highly inbred Drosophila strains].
AB  - The results of three long-term breeding and genetic experiments with Drosophila
      melanogaster performed at different times are summarized. Selections for
      different fitness components led to similar results. The data on the
      concentration of viability mutations in the inbred strains LA, LA+, and LA- after
      400 generations of selection and the strain ULA during its breeding are presented
      for the first time. The results of studying the genetic heterogeneity and
      spontaneous mutational process in Drosophila inbred strains comply with the idea
      of M.E. Lobashev that "a change in the direction of selection or acceleration of
      its rate is always accompanied by a concurrent increase in mutational variation".

PMID- 18069338
TI  - [Basic aspects of ovarian development in Drosophila melanogaster].
AB  - Modern views of the development and structural organization of the female
      reproductive system in Drosophila melanogaster are reviewed. Special emphasis is
      placed on the generation and development of follicles in the germarium and the
      interactions of germline and somatic cells in the egg chamber. Detailed
      consideration is given to the main events that ensure and regulate the transport
      of mRNA, proteins, and organelles from nurse cells to the oocyte in the germarium
      and at later stages of egg chamber development.

PMID- 18069339
TI  - [Biochemical genetics in St. Petersburg university: from the gene-enzyme model to
      medical biotechnology].
AB  - The history of biochemical genetic research in St. Petersburg (Leningrad) State
      University is described. The main research projects and achievements of the
      Laboratory of Biochemical Genetics in studies on the mechanisms of gene
      expression control, coordinated regulation of metabolism, and the relationship of
      the physiological state of yeast cells with the maintenance of genetic stability
      are discussed. The fundamental importance of studies on the acid phosphatase
      model for the formation and development of medical biotechnology in St.
      Petersburg University is demonstrated.

PMID- 18069340
TI  - [Viable nonsense mutants for the SUP45 gene in the yeast Saccharomyces cerevisiae
      are lethal at increased temperature].
AB  - Nonlethal nonsense mutations obtained earlier in the essential gene SUP45
      encoding the translation termination eRFI factor in the yeast Saccharomyces
      cerevisiae were further characterized. Strains carrying these mutations retain
      the viability, since the full-length eRF1 protein is present in these strains,
      although in decreased amounts as compared to wild-type cells, together with a
      truncated eRF1. All nonsense mutations are likely to be located in a weak
      termination context, because a change in the stop codon UGAA (in the case of
      mutation sup45-107) to UAGA (sup45-107.2) led to the alteration of the local
      context from a weak to strong and to the lethality of the strain carrying sup45
      107.2. All nonsense mutations studied are characterized by thermosensitivity
      expressed as cell mortality after cultivation at 37 degrees C. When grown under
      nonpermissive conditions (37 degrees C), cells of nonsense mutants sup45-104,
      sup45-105. and sup45-107 display a decrease in the amount of the truncated eRF1
      protein without reduction in the amount of the full-length eRF1 protein. The
      results of this study suggest that the N-terminal eRF1 fragment is indispensable
      for cell viability of nonsense mutants due to the involvement in termination of
      translation.

PMID- 18069341
TI  - [Removing endosymbiotic Wolbachia specifically decreases lifespan of females and
      competitiveness in a laboratory strain of Drosophila melanogaster].
AB  - To understand specific symbiotic relationships ensuring stable existing of the
      bacterium Wolbachia in laboratory strains of Drosophila melanogaster, the imago
      lifespan and senescence rate, as well as competitiveness, have been evaluated as
      components of fitness in females from the following laboratory strains: (1)
      inbred strain 95 infected with Wolbachia; (2) two uninfected strains obtained by
      tetracycline treatment that were genetically similar to strain 95; and (3) two
      control, uninfected, wild-type laboratory strains that were used to assess the
      possible effects of the antibiotic on the studied characters in the absence of
      Wolbachia. The results have shown that infected females have longer lifespan and
      competitiveness than females with the same genotype uninfected with Wolbachia.
      The increase in the senescence and mortality rates with age was also slower in
      infected females. It is noteworthy that tetracycline does not affect the lifespan
      of females from the two control, uninfected, wild-type strains. Therefore, the
      antibiotic is not the cause of the positive changes in fitness that were observed
      in infected females. The obtained results are the first direct evidence that the
      relationship s in the Wolbachia-D melanogaster symbiotic system are mutualistic
      rather than parasitic, at least in micropopulations adapted to laboratory
      conditions.

PMID- 18069342
TI  - [Hyperthermia of male Drosophila melanogaster meiocytes induces abnormalities in
      both paternal and maternal sex chromosome sets of the offspring].
AB  - Nondisjunction and loss of sex chromosomes caused by exposure of male Drosophila
      melanogaster to heat shock (HS) (37 degrees C for 1 h) has been studied to
      determine the role of mutation l(1)ts403 (sbr10) in the control of chromosome
      segregation during cell division. Hyperthermia of males at the pupal stage has
      been demonstrated to increase the number of offspring with abnormalities of not
      only paternal, but also maternal sex chromosome sets. According to the criterion
      used, there is a temperature-sensitive period of spermatogenesis, which
      presumably coincides with meiosis. Phenotypes of some individuals correspond to
      the presence of two sex chromosomes of obtained from the same parent. The
      frequency of abnormal chromosome sets in the offspring of male carriers of the
      sbr10 mutation is about two times higher than in the offspring of males without
      this mutation.

PMID- 18069343
TI  - [Evolution of errantiviruses of Drosophila melanogaster. Strategy 2: from
      retroviruses to retrotransposons].
AB  - Drosophila melanogaster retrotransposons of the gypsy group are considered to be
      potential errantiviruses. Their infectivity is caused by the functional activity
      of the third open reading frame (ORF3) encoding the Env protein, which was
      probably captured from baculoviruses. Mobile genetic elements (MGEs) of the gypsy
      group can be conventionally divided into three subgroups: with three ORFs, with a
      defective ORF3, and without the ORF3. To establish the patterns of evolution of
      gypsy retrotransposons in D. melanogaster, the members of the three subgroups
      were examined. Structural analysis of retrotransposons opus and rover, which
      carry a defective ORF3, as well as retrotransposons Burdock, McClintock, qbert,
      and HMS-Beagle, which lack the ORF3, suggests that the evolution of these MGEs
      followed the pattern of loosing the ORF3. At the same time, an MGE of the same
      subgroup, Transpac, may be an ancestral form, which had acquired the env gene and
      gave rise to the first errantiviruses. The capture of the ORF3 by
      retrotransposons provided their conversion to a fundamentally new state. However,
      the ORF3 in the genome is not subjected to strong selective pressure, because it
      is not essential for intragenomic transpositions. Because of this, the process of
      its gradual loss seems quite natural.

PMID- 18069344
TI  - [Mutations in structural genes of tryptophan metabolic enzymes of the kynurenine
      pathway modulate some units of the L-glutamate receptor--actin cytoskeleton
      signaling cascade].
AB  - Methods of immunohistochemistry and fluorescent staining was used to study the
      localization and amounts of protein components of the signal cascade connecting
      the receptor link (NMDA-subtype glutamate receptor) with actin of the
      cytoskeleton in the head ganglia of Drosophila strain Canton-S (wild type,
      control) and strains carrying mutations vermilion, cinnabar, and cardinal, which
      sequentially inactivate tryptophan-hydrolyzing enzymes during its metabolism into
      ommochrome. The obtained data are evidence for modulatory effects of genes
      controlling the kynurenine pathway of tryptophan metabolism on the major
      components of the signal cascade: the initial link (NMDA receptor, postsynaptic
      density protein-95, a structural protein involved in receptor localization and
      internalization), the intermediate link (limkinase-l, the key neuronal enzyme in
      actin remodeling) and the final link (f-actin, the critical factor in the
      morphogenesis of synaptic structures and, hence, in the processes of synaptic
      plasticity, learning and memory). It is suggested that kynurenine acid (an
      endogenous nonspecific antagonist of L-glutamate receptor) and 3
      hydroxykynurenine capable of inducing a nonspecific stimulating effect are
      biochemical intermediates of the effects of these genes.

PMID- 18069345
TI  - [Prospects of using self-fertility in breeding rye populations varieties].
AB  - The advances in rye hybrid breeding are due to the use of self-fertile forms. Rye
      self-fertility is determined by mutations in one of the three gametophytic loci
      (S, Z, and T), which control the reaction of incompatibility. Attempts to
      construct synthetic populations by combining self-fertile forms selected by
      general combining ability failed because of high-rate selfing. A breeding scheme
      was proposed to include crosses of a line carrying a self-fertility mutation in
      the S locus with the population subject to improvement, selfing of the resulting
      hybrids, selection and intermating of the best inbred progenies, and subsequent
      elimination of the self-fertility mutation from the breeding material with the
      use of the Prx7 allozyme marker. The scheme can be employed in improvement of the
      existing rye varieties, their differentiation into populations differing in end
      use, and construction and improvement of complementary gene pools in hybrid
      breeding. To facilitate the implementation of the scheme, an original instrument
      was designed for high-throughput isozyme analysis.

PMID- 18069346
TI  - [The genetic collection of radish inbred lines: history and prospects].
AB  - The characteristics of a unique genetic collection of radish inbred lines and the
      history of its creation and study are presented. The possible research prospects
      are discussed.

PMID- 18069347
TI  - [Expression and inheritance of a desynaptic phenotype with impaired homologous
      synapsis in rye].
AB  - The cytological phenotype was studied in a desynaptic form isolated from a
      population of rye cultivar Vyatka. The primary defect of desynaptic plants was
      identified as nonhomologous (heterologous) chromosome synapsis, which was
      observed by electron microscopy of synaptonemal complexes (SCs) in meiotic
      prophase I. Synapsis defects involved switches of synapsing axial elements to
      nonhomologous partners, asynapsis in the switching region, and foldbacks formed
      by the SC lateral elements. Defective bivalent formation was observed at later
      stages: the univalent number varied and multivalent chromosome associations were
      observed in single cells in metaphase I. The desynaptic phenotype was controlled
      by two recessive genes, sy8a and sy8b, which acted and were inherited
      independently. In a hybrid combination with line Ku-2/63, the desynaptic
      phenotype was suppressed by the dominant allele of a third gene for inhibitor I;
      the segregation in hybrid families corresponded to 57:7.

PMID- 18069349
TI  - [Normal sleep].
AB  - Sleep represents organized complex behavior necessary and vital for the survival
      of the species. It is reversible, internally regulated and homeostatically
      controlled process. Sleep consists of two separate states designated as NREM and
      REM sleep. NREM sleep has four sleep states (1 through 4) easily defined by the
      PSG and EEG components. REM sleep consists of tonic and phasic components. The
      tonic component of REM sleep by default includes the duration while phasic
      component consists of clusters of rapid eye movement, muscle twitches and PGO
      activity. The two states of sleep differ fundamentally both from one another as
      well as from the state of wakefulness. NREM and REM sleep is organized in sleep
      cycles with a typical duration between 90 and 110 minutes. Approximately 4 to 6
      cycles emerge during the night with the REM episodes being prolonged towards the
      morning. About 70-80% of sleep process belongs to NREM and 20-25% to REM sleep.
      Normal aging carries the reduction in slow high-voltage activity (delta sleep)
      while REM sleep is of the relatively constant duration. Overall, sleep in elderly
      is characterized by the increase in the number of sleep stage shifts, increase in
      the number of awakenings and a shift towards the superficial sleep stages.

PMID- 18069348
TI  - [Polymorphism of the apolipoprotein E gene (APOE) in the populations of Russia
      and neighboring countries].
AB  - Allele and genotype frequencies for the locus encoding apolipoprotein E, involved
      in the regulation of lipid metabolism (APOE), were evaluated in 16 populations
      representing 12 ethnic groups (a total of 1103 subjects) from Russia and
      neighboring countries. In the populations examined, the frequencies of allele
      epsilon4, which is the risk factor of Alzheimer's disease and coronary heart
      disease, varied from less than 5 to more than 20%, while the variation of the
      major epsilon3 allele in these populations ranged from less than 75 to 95%. The
      frequencies of alleles epsilon3 and epsilon4 were 0.714 and 0.205 in Saami, 0.734
      and 0.149 in Maris, 0.841 and 0.122 in Evenks, 0.788 and 0.163 in Buryats, 0.764
      and 0.202 in Chukchi, 0.875 and 0.075 in Iranians, 0.956 and 0.044 in mountain
      dwellers of the Pamirs, 0.771 and 0.094 in Ukrainians, and 0.795 and 0.091 in
      Belarussians, respectively. In Russians from different regions of the country,
      the frequencies of these alleles were 0.728 and 0.139 (Kostroma), 0.795 and 0.105
      (Moscow), 0.857 and 0.092 (Rostov-on-Don), and 0.824 and 0.083 (Krasnodar),
      respectively. The latitudinal distribution of the APOE epsilon3 and epsilon4
      allele frequencies in the populations examined was comparable to the frequency
      distribution pattern of these alleles in other populations of Eurasia.

PMID- 18069350
TI  - [A contemporary view at the classification of sleep disorders].
AB  - Sleep disorders although relatively new multidisciplinary territory in the field
      of medicine, have rather well developed classification system and nosology owing
      to the constant work of the American Academy for Sleep Medicine as well as the
      European, Japanese and Latin-American societies for sleep research. This
      collaboration produced the International classification of Sleep Disorders (ICSD)
      that has recently met its second revision. At the same time the International
      Classification of Diseases of the World Health Organization gives codes and
      enables statistical elaboration of a large number of sleep diseases. Differences
      between these two systems exist reflecting the basic principle used in their work
      out.

PMID- 18069351
TI  - [Epidemiology of sleep disturbances].
AB  - Epidemiological studies indicate that sleep disturbances in general population
      are highly frequent. It is estimated that approximately 40 million people in the
      USA has some kind of problem with sleep. The most frequent sleep complaint is
      insomnia whose prevalence is around 50% some time in the life. Only a small part
      of this population refer their sleep problems to the medical doctor with the
      consequence that only a minority is adequately diagnosed and treated. Sleep
      problems may appear at any age, and the epidemiological studies indicate the
      increase of specific prevalence with advancing age, with a special increase in
      the adults. It is estimated that the prevalence of sleep problems in childhood
      and adolescence is present in 25-40%. Some of the problems are more frequent in
      the female population, although not as a rule. The best example for this is the
      observed prevalence of sleep apnea which is present in 24% of male and only 9% of
      female population. Sleep problems are often associated with other diseases such
      as psychiatric or kidney diseases (patients on hemodialysis). However, their
      frequency may increase in physiologic conditions such as pregnancy. Overall
      characteristic of sleep diseases is that they may compromise daily functioning by
      causing deficits in memory, decrease in concentration, depressive mood,
      irritability, decreased libido or erectile dysfunction, having as a consequence
      decrease in the quality of life.

PMID- 18069352
TI  - [Narcolepsy and other hypersomnias].
AB  - This article gives an overview of a few most significant but also most frequent
      primary hypersomnias in humans. The prevalence of hypersomnia in USA is between
      0.3 and 16.3% which is close to its prevalence in Europe which is 5-16%. The
      prevalence of narcolepsy with cataplexy in USA and the countries of Western
      Europe is from 0.05-0.067%. Its presence is significantly higher in Japan and
      lower in Israel. Most of the symptoms of narcolepsy represent the abnormal
      manifestations of dissociated REM sleep process. Excessive daytime sleepiness,
      sleep attacks and cataplexy are the most frequent symptoms. The diagnosis of
      narcolepsy should be confirmed by a whole-night polysomnographic recording
      followed by a Multiple sleep latency test. Idiopathic hypersomnia is a rare
      disease (ten times as rare as narcolepsy) with the diagnostic procedure similar
      to that of narcolepsy. Treatment of hypersomnias is symptomatic with the aimed to
      reduce the most frequent symptoms (excessive daytime sleepiness, sleep attacks,
      cataplexy and hypnagogic/hypnapompic sleep paralyses).

PMID- 18069353
TI  - [REM sleep parasomnias and degenerative diseases of the central nervous system].
AB  - Parasomnias are defined as unpleasant and undesirable behavioral (in the sense of
      action) or experiential (in the sense of sensorial or perceptive) phenomena which
      overwhelmingly or exclusively happen during sleep. Former attitudes that
      parasomnias are closely related to psychiatric derangement are abandoned and
      newer polysomnographic research indicates that we are dealing with a number of
      totally different organically defined states, most of which are easy to diagnose
      and even cure. The frequency of parasomnias in population is much higher than so
      far supposed so that they are considered among the most frequent disturbance of
      the CNS. Another inglorious record tightly connected to parasomnias is that they
      belong to the most frequently undiagnosed or misdiagnosed diseases. Clinically
      the most important and intriguing of the parasomnias associated with REM sleep,
      is REM sleep behavior disorder (RBD). In the last few decades in the field of
      human and animal sleep, researchers have noticed that RBD represents the omen of
      the more complex degenerative disorders of the central nervous system--the
      synucleinopathies and tauopathies. RBD can precede these disorders for decades
      before the florid clinical picture becomes obvious.

PMID- 18069354
TI  - [Is pharmacologic treatment of sleep apnea efficient?].
AB  - High frequency of sleep disturbed breathing in adults is increasingly recognized.
      Obstructive sleep apnea, defined as the recurring obstruction of the upper airway
      is documented in 24% of adult males and 9% of females. The highest incidence is
      in the sixth decade. Snoring accompany 24% of middle aged man and 14% of females
      of the same age. Sleep apnea with the central origin, defined as the transient
      and recurrent cessation of breathing during sleep, is less frequent than
      obstructive sleep apnea. It can be identified in the wide spectrum of patients
      with medical, neurologic and neuromuscular diseases tightly connected with
      alveolar hypoventilation.

PMID- 18069355
TI  - [How to solve the problem of sleep apnea?].
AB  - The future of solving the problem of sleep apnea necessitates the systematic
      organization of activities that would include: 1) increase in the awareness of
      the significant prevalence of sleep apnea and its influence on health and
      economic burden in the population via media and educational campaign; 2)
      establishment of the work groups that will find the answers and set the
      scientific research according to the needs posed by the sleep diseases; 3) Check
      the existing and develop new diagnostic and therapeutic methods with special
      reference to home monitoring with the creation of the national research network
      which will connect researchers and their programs and research centers; 4)
      Organization at the national level of educational centers and laboratories that
      will adequately respond to the needs of the pathology present in the population.

PMID- 18069356
TI  - [Ghrelin and sleep].
AB  - Human sleep is characterized by cycling of non-rapid-eye-movement sleep (NREMS)
      and rapid-eye-movement sleep (REMS) during which the secretion of different
      hormones has certain characteristics. During the first half of the night there is
      characteristic increase in growth hormone and at the same time decrease in ACTH
      and cortisole. Conversely, in the second part of the night there is an increase
      in ACTH and cortisole and the secretion of growth hormone is decreased. These
      facts indicate that there exist a reciprocal interaction of the hypothalamo
      pituitary-somatotrophic axis and hypothalamo-pituitary-adrenal axis on one side
      and a common regulatory factors for EEG changes during sleep and nocturnal
      hormone secretion on the other. It follows that the reciprocal interaction of two
      key hormones of the hypothalamo-pituitary-somatotrophic axis (GHRH) and
      hypothalamo-pituitary-adrenal axis (CRH) have a fundamental role in the
      regulation of sleep.

PMID- 18069357
TI  - [Sleep and the epilepsies].
AB  - Interrelationship between sleep and epilepsy presents in the best way the
      delicate konjuction of physiologic and pathologic mechanisms underlying both of
      the states. In the II century it was Galen who pointed to the detrimental effect
      of sleep deprivation on the frequency of epileptic attacks. This empiric
      formulation is important even today in the counceling of patients with epilepsy.
      The research of the sleep process generated better understanding of the basic
      mechanisms of epilepsies. Sleep deprivation worsens the control of epileptic
      attacks which in turn destroy sleep structure and impede the daily functioning of
      the epileptic patients.

PMID- 18069358
TI  - [Psychiatric aspects of sleep].
AB  - Sleep disturbances are frequently the consequence of physiological and
      psychological problems and may be classified in three groups: diminished total
      quantity of sleep, loss of the quality and inadequate timing of the sleep
      process. It is considered that one third of the population has a sleep
      disturbance some time in the life. Insomnia is the most frequent sleep
      disturbance but timely and careful diagnostic procedure is fundamental for the
      specific treatment. Factors connected with the increased prevalence of sleep
      disturbance are female gender, presence of mental or somatic diseases and
      advanced age. Sleep disturbances are classified in four basic groups:
      insufficient quantity or unrestorative sleep (insomnia); prolonged sleep
      (excessive daily somnolence or hypersomnia); problems with timing of sleep and
      problems close to or within the sleep process (parasomnias).

PMID- 18069359
TI  - [Disturbed motor behavior in sleep].
AB  - Although majority of skeletal muscles displays reduced tonic activity during
      sleep it is well known that the body during sleep is not motionless. Studies from
      the beginning of the past century established that the contractions of the muscle
      groups and the movements of the body are the consequence of the influence of the
      afferent stimuli from periphery generated by the sleeper in an endeavor to ensure
      a better position of the body and a better sleep quality. The number of body
      movements represent the individual trait of the sleeper. Aside from the
      contractions of the large muscle groups, sleep can generate short lasting
      contractions of the distal muscles (fingers, muscles of the face) that could be
      detected at the beginning of the sleep process or in REM sleep. Though all these
      movements could be seen in healthy individuals, their existence may be a part of
      the disease and involuntary movements seen during the process of sleep, and then
      they differ from normal ones in their frequency, timing and distribution of the
      affected muscle groups.

PMID- 18069360
TI  - It's all about relationships.

PMID- 18069361
TI  - Amish outreach improves health status, collections.

PMID- 18069362
TI  - Oral health status and prosthodontic conditions of Chinese adults: a systematic
      review.
AB  - PURPOSE: To assess oral health and prosthodontic conditions of Chinese adults and
      the changes in these conditions over time. MATERIALS AND METHODS: PubMed was
      searched by combining the keyword China with dental health survey, oral health,
      tooth loss, DMFT (decayed/missing/filled teeth), dental prosthesis, or dentures.
      After selection, 12 studies remained. Data were obtained from these studies on
      DMFT, DMFT components, and teeth present and were tested against the following
      independent variables using analysis of variance: age, residence, and year of
      data collection. RESULTS: DMFT increased with age (P = .0001). Rural subjects
      presented higher DMFT based on the higher "decayed" component (P = .003), which
      increased markedly for subjects over 45 years of age. The number of teeth present
      decreased with increasing age (P = .0002). The results showed that Chinese
      subjects who are 65 years old have an average of 20 teeth. Urban subjects had
      more teeth present (P= .05), although no difference was seen for the "missing"
      component of DMFT. In general, few prosthodontic data could be extracted from the
      selected studies, and these data were often unspecific or inconclusive.
      CONCLUSIONS: The "filled" component of DMFT remained consistently low for all
      ages, indicating limited care. All outcomes were independent from year of data
      collection, indicating unchanged care. Outcome aggregation on the number of
      functional teeth and prosthetic care was impossible. For future reports, it is
      recommended to include additional information about location and function (in
      terms of occluding pairs) of teeth present when describing oral health status.

PMID- 18069363
TI  - Dimensional accuracy of 2-stage putty-wash impressions: influence of impression
      trays and viscosity.
AB  - The aim of this in vitro study was to evaluate the influence of the impression
      tray and viscosity of the wash material on the dimensional accuracy of
      impressions taken using a 2-stage putty-wash technique. Identically shaped metal
      stock trays (MeTs) and disposable plastic stock trays (DiTs) were used for taking
      impressions (n = 10) of a mandibular cast (4 abutments) with 2 different
      impression materials. Dies were poured and the relative diameter deviation was
      calculated after measurement. Zero viscosity of the materials was determined.
      Dimensional accuracy was significantly affected when DiTs were used. Lower
      viscosity wash materials led to more precise impressions.

PMID- 18069364
TI  - Treatment with double crown-retained removable partial dentures and oral health
      related quality of life in middle- and high-aged patients.
AB  - The objective of this study was to assess the change in oral health-related
      quality of life following treatment with double crown-retained removable partial
      dentures (RPDs). Sixty RPDs in 54 patients (mean age: 65 years) were fabricated
      and retained with either galvanoformed telescopic secondary crowns (n = 30) or
      conical secondary crowns (n = 30). The Oral Health Impact Profile (OHIP) was
      assessed pretreatment and during 6- and 12-month follow-up appointments. Patient
      assessment of denture-satisfaction was also recorded on a Lickert-type scale. A
      decrease in the OHIP-sum score was significant after treatment for both groups,
      but not between the experimental groups. The denture assessment showed good
      values for both groups. Treatment with different double crown-retained RPDs
      improved oral health-related quality of life.

PMID- 18069365
TI  - The influence of gender and age on fixed prosthetic restoration longevity: an up
      to 18- to 20-year follow-up in an undergraduate clinic.
AB  - PURPOSE: This study investigated the possible relationship between the survival
      of complete crowns (CCs), 3-unit fixed dental prostheses (3uFDPs), and fixed
      dental prostheses (FDPs) versus gender and age at initial treatment over a period
      of 18 to 20 years in an undergraduate clinic. MATERIALS AND METHODS: Complete
      treatment and follow-up records of 1,037 CCs (60.5% women/39.5% men; age range:
      18 to 82 years), 134 3uFDPs (59.2% women/40.8% men; age range: 33.6 to 93.6
      years), and 322 FDPs (62.1% women/37.9% men; age range: 33.6 to 94.2 years) were
      available for analysis. Failures of the fixed prosthetic restorations were
      defined as irreversible complications (finish line involved or loss of CCs, FDPs,
      or abutments). RESULTS: The association between gender versus irreversible
      complications for the CCs (P = .481), 3uFDPs (P= .814), and FDPs (P = .410)
      groups was not statistically significant. The relationship between age versus
      irreversible complications for the fixed prosthetic restorations was
      statistically significant for all test groups. The patients with the failing
      restorations (66.2 years; mean range: 64.8 to 67.5 years) were 4.5 to 5.5 years
      older at initial treatment than the patients with the surviving restorations
      (61.3 years; mean range: 59.5 to 63.0 years). CONCLUSIONS: There was no
      relationship between gender and irreversible complications. There was a clear
      statistically significant association between age and irreversible complications.
      Receiver operating characteristic analysis for all study groups revealed that for
      age, no clear cutoff point exists with acceptable specificity and sensitivity.

PMID- 18069366
TI  - Chemical solubility and flexural strength of zirconia-based ceramics.
AB  - PURPOSE: This study was undertaken to investigate the chemical solubility and
      flexural strengths of 3 zirconia-based dental ceramics: In-Ceram Zirconia (IZ),
      In-Ceram 2000 YZ CUBES (YZ Zirconia) (Vita Zahnfabrik), and Cercon (Dentsply). A
      pressable lithium disilicate-reinforced glass ceramic (IPS Empress 2, Ivoclar
      Vivadent) was used as a control. MATERIALS AND METHODS: Ten block specimens (12 x
      6 x 4 mm) of each ceramic material were prepared for chemical solubility testing.
      Each specimen was refluxed in 4% acetic acid solution for 16 hours. The
      percentage loss of mass and the loss of mass per unit of surface area for each
      specimen were calculated. Ten bar-shaped (21 x 5 x 2 mm) and 10 disk-shaped (16
      mm diameter, 1.2 mm thickness) specimens of each ceramic material were prepared
      and tested for uniaxial flexural strength (UFS) and biaxial flexural strength
      (BFS). X-ray diffraction analyses were conducted to determine the relative amount
      of the monoclinic phase of the as-sintered and fractured surfaces of the zirconia
      ceramics. RESULTS: There were no significant differences among the ceramics in
      chemical solubility by percentage mass or mass/surface area. For UFS, YZ Zirconia
      (899 +/- 109 MPa) > Cercon (458 +/- 95 MPa) IZ (409 +/- 60 MPa) > Empress 2 (252
      +/- 36 MPa). For BFS, YZ Zirconia (1,107 +/- 116 MPa) > Cercon (927 +/- 146 MPa)
      > IZ (523 +/- 51 MPa) > Empress 2 (359 +/- 43 MPa). The fractured YZ Zirconia
      surface contained approximately 5 times as much monoclinic phase compared to that
      of its intact surface. The fractured IZ and Cercon surfaces contained
      approximately twice as much monoclinic phase compared to those of intact
      surfaces. CONCLUSION: The ceramics tested all satisfied the chemical solubility
      allowance required of core ceramic material (type I, Class 1 or type II, Class 1)
      according to the International Organization for Standardization 6872:1995(E)
      specifications on dental ceramic. The zirconia-based ceramics possessed
      significantly higher flexural strengths than the control lithium disilicate
      ceramic. Their clinical application appears sufficiently promising for long-term
      clinical studies to be undertaken.

PMID- 18069367
TI  - Cytotoxic effects of veneer composite materials.
AB  - The aim of this study was to evaluate 4 veneer composites-Signum+EM, Gradia
      Enamel E3, Sinfony E3, and SR Adoro S1-in a standardized test at 2 different
      conditions. For each composite, 2 groups of specimens (added to cultures
      immediately after preparation [ie, fresh] or after 7 days of incubation in cell
      culture medium) were added to L-929 fibroblast cultures for 72 hours. All
      composites showed reduced cell numbers compared to glass controls. Fresh
      specimens of Signum+EM exhibited the least cytotoxicity, followed by Gradia
      Enamel E3 and Sinfony E3 and then SR Adoro S1. For specimens with 7-day
      incubation, 3 of the composites (Signum+EM, Sinfony E3, and Gradia Enamel E3)
      showed similarly low cytotoxicity, while cytotoxic results with SR Adoro S1 were
      significantly higher. With low in vitro toxicity values in conjunction with good
      mechanical properties, veneer composites appear to offer an interesting
      alternative for prosthetic rehabilitation.

PMID- 18069368
TI  - Temporomandibular disorders and associated factors in Brazilian teenagers: a
      cross-sectional study.
AB  - PURPOSE: This study aimed to assess the prevalence of temporomandibular disorders
      (TMD) and associated variables among adolescents from 16 to 18 years of age in
      their senior year of high school in the city of Recife, Pernambuco, Brazil, in
      2005. MATERIALS AND METHODS: The studied variables were gender, self-esteem and
      nervous behavior, type of occlusion, and use of orthodontic appliances. In this
      cross-sectional study, the nonpatient population comprised 410 adolescents
      attending private and state schools. The data collection was conducted using 2
      questionnaires, the first of which was used to evaluate the prevalence of TMD and
      the second to assess self-esteem. A clinical examination was conducted for the
      occlusion aspect of the evaluation. RESULTS: The prevalence of TMD was 16.3% in
      the study group and there was no statistical difference between occlusions judged
      as normal or as malocclusions (P = .1148). There was a statistically significant
      association between students who had previously undergone orthodontic treatment
      and TMD (P = .0033, odds ratio: 3.08). The students classified in the low self
      esteem group showed a significant increase in TMD (P= .0140). The group that
      classified themselves as nervous also showed an increase (P = .0034), with a
      higher prevalence also found in females (P = .0021). CONCLUSIONS: This study
      suggests that low self-esteem and gender may be more frequently related than
      dental factors to TMD in adolescents.

PMID- 18069369
TI  - Clinical decision-making practices among a subset of North American
      prosthodontists.
AB  - The aim of this study was to determine the decision-making practices of a subset
      of North American prosthodontists. A survey was administered to assess
      practitioner views regarding the relative importance of practitioner, patient,
      and patient family beliefs and preferences during treatment planning of the
      edentulous patient. In responses to abstract questions, practitioners appeared to
      endorse a blending of patient and practitioner beliefs and preferences when
      treatment planning. However, in response to a question proposing a simulated
      clinical scenario, practitioners indicated they placed a greater emphasis on
      their own beliefs when choosing a treatment option.

PMID- 18069370
TI  - A 4- to 6-year retrospective clinical study of cracked teeth restored with bonded
      indirect resin composite onlays.
AB  - PURPOSE: The purpose of this study was to retrospectively evaluate the clinical
      performance of bonded indirect resin composite onlays for the treatment of
      painful, cracked teeth over a 6-year period. MATERIALS AND METHODS: Forty-three
      posterior teeth diagnosed as having a crack were selected in the restorative
      department of the University of Genoa. Inclusion criteria were sensitivity to
      biting and cold and a clinically visible crack. Direct composite buildup after
      removal of the existing restoration was performed before definitive cavity
      preparation. All composite onlay restorations were cemented with an adhesive
      technique using a 3-step total etch system and a dual-cure composite cement.
      Patients were interviewed and clinically examined at 1 week, 4 weeks, and every 6
      months. RESULTS: The effectiveness of bonded onlay restorations was evaluated for
      a mean observation time of 4.78 years. At 1 week, 38 (88.37%) restored teeth were
      free of pain, 3 (6.98%) still had sensitivity to cold, and 2 (4.65%) still had
      sensitivity to cold and chewing. At 4 weeks, 40 (93.02%) teeth were free of pain,
      2 (4.65%) still had sensitivity to cold and chewing, and 1 (2.32%) needed
      endodontic treatment. Two other teeth (4.65%) also needed endodontic treatment,
      the first after 2 months and the second after 5 months. During the evaluation
      period, 3 restorations (6.98%) failed, and upon clinical examination, 40 (93.02%)
      teeth were free of symptoms with a 6-year survival rate of 93.02% (life table
      analysis). CONCLUSIONS: Bonded indirect resin composite onlays can be successful
      in treating painful, cracked teeth. From the findings of this study, it appears
      that cuspal protection should be incorporated into the design of coronal
      restorations.

PMID- 18069371
TI  - Dental implants as strategic supplementary abutments for implant-tooth-supported
      telescopic crown-retained maxillary dentures: a retrospective follow-up study for
      up to 9 years.
AB  - PURPOSE: The aim of this retrospective study was to present the results of
      implants and natural teeth used as combined abutments to support maxillary
      telescopic prostheses. MATERIALS AND METHODS: Between 1997 and 2004, 22 patients
      with residual maxillary teeth underwent prosthodontic rehabilitation with
      supplementary implant placement of implant-tooth-supported telescopic prostheses.
      A total of 60 supplementary implants (mean: 2.9 implants; SD: 1.6; range: 1 to 5
      per patient) were placed in strategic position and connected with 48 natural
      abutment teeth (mean: 2.2 teeth; SD: 0.9; range: 1 to 4 per patient) using
      telescopic crowns. The follow-up registration included implant and natural tooth
      survival rates and peri-implant and periodontal parameters, along with
      prosthodontic maintenance. Natural tooth abutments were additionally followed to
      compare their periodontal parameters at baseline to the follow-up examination.
      RESULTS: After a mean of 38 months (12 to 108 months) no implants or natural
      tooth abutments were lost (survival rate: 100%). There was no fracture,
      endodontic treatment, loss, or intrusion of natural teeth used for telescopic
      abutments. Implant abutments showed high stability and excellent periimplant soft
      tissue conditions. Natural tooth abutments used for double crowns also showed
      uneventful progress. A low rate of prosthodontic maintenance was seen, with
      implant screw abutment loosening as the most severe complication (3 of 60
      implants; 5%). CONCLUSIONS: On the basis of this retrospective clinical review,
      the following conclusions were drawn: (1) successful function over a prolonged
      period and a minor complication rate of implant-tooth-supported telescopic
      maxillary dentures may be anticipated, and (2) the great variety of treatment
      modalities offered by tooth-implant support for telescopic prostheses appears to
      be useful as a treatment option for the maxilla in elderly patients.

PMID- 18069372
TI  - Influence of connection geometry on dynamic micromotion at the implant-abutment
      interface.
AB  - The aim of this study was to evaluate dynamic micromotion at the implant-abutment
      interface for 3 different implant neck designs. Five samples each from 3 implant
      types with different neck designs were subjected to 1 x 10(6) cycles under
      simulated oral conditions. Load magnitudes varied from 10 to 250 N at 15 Hz. The
      results revealed a significant main effect for type of implant (P < .0001). The
      main effect for level of cycles proved to be nonsignificant (P = .9999), as did
      the interaction between type of implant and level of cycles (P = .9989).
      Differences in neck design among the 3 implant types resulted in differences in
      micromotion at the implant-abutment interface under simulated oral conditions.

PMID- 18069373
TI  - Tooth movements adjacent to single-implant restorations after more than 15 years
      of follow-up.
AB  - PURPOSE: To analyze the prevalence and magnitude of tooth movements adjacent to
      single-implant crowns in a long-term study, and to discuss these changes in
      relation to changes in cephalometric measurements of a reference group after 10
      years. MATERIALS AND METHODS: Twenty-five of an original group of 39 patients,
      consecutively restored with single-implant crowns in the anterior maxilla, were
      included. The mean age was 25.4 years (SD: 10.0) at inclusion. Clinical
      photographs were taken at implant crown placement and at the final examination an
      average of 15.9 years (SD: 0.74) later. The reference group comprised 134 dental
      students with a mean age of 22.9 years (SD: 1.20) at inclusion. Cephalograms and
      study casts were made at inclusion and after 10 years. Study casts were also made
      after 20 years (n = 61). Tooth movements were assessed adjacent to the implant
      crowns according to a clinical index. For the reference group, cephalometric
      measurements were performed for anterior and posterior face height and gonion and
      nasion-sella line/mandibular line (NSL/ML) angles. Vertical overbite measurements
      were collected from the study casts. RESULTS: Altogether, 28 implant crowns were
      included in the test group. Male patients presented a clinically stable situation
      without any signs of vertical tooth movement adjacent to the single-implant
      restorations in 11 of 20 implant sites, compared to none in female patients (P <
      .05). With regard to horizontal tooth movements, 55% of the sites showed palatal
      tooth movements, which were relatively more common in females. Both males and
      females presented a significant average increase of anterior and posterior face
      height (P < .05), but only females presented a significant increase of the NSL/ML
      angle. Average vertical overbite was basically stable for 20 years, but
      individual variations were obvious. CONCLUSIONS: A possible relationship between
      significantly higher incidence of tooth movements adjacent to implants in females
      in the study group and significantly greater increase of anterior face height and
      posterior rotation of the mandible in the female reference group was observed.

PMID- 18069374
TI  - Survival rates of endodontically treated teeth restored with fiber-reinforced
      custom posts and cores: a 97-month study.
AB  - PURPOSE: This study aimed to assess the long-term survival rates of polyethylene
      fiber-reinforced posts and cores used in endodontically treated teeth over a 97
      month period. MATERIALS AND METHODS: Sixty-nine patients from a private dental
      office who underwent endodontic treatment with coronoradicular fiber-reinforced
      restorations were selected and invited for evaluation. All teeth were restored
      with the same high-molecular-weight polyethylene fiber (Ribbond, Ribbond Inc) and
      resin composite cement (Enforce, Dentsply) post-and-core system by a single
      operator and then prepared and restored with complete cast crowns or direct resin
      composite. Survival functions of restorations were analyzed with Kaplan-Meier and
      log-rank tests (alpha = .05) and displayed according to the variable tooth
      location and material of the definitive restoration. RESULTS: Four posts
      fractured among the 36 anterior restorations evaluated, and 2 posts fractured
      among the 73 posterior restorations. The mean overall survival estimate was 90.2
      (+/- 3.7) months (95% Cl: 82.8-97.5). There were no differences between survival
      functions regarding tooth location or type of restorative material as variables
      (P> .05). CONCLUSIONS: The results suggest that polyethylene fiber-reinforced
      posts with composite cores may be recommended for clinical use. Restorations
      evaluated in this study presented high survival rates after the 97-month follow
      up period.

PMID- 18069375
TI  - The proportion of 3 classes of lateral throat form.
AB  - The aim of this study was to investigate the proportion of 3 Neil's
      classifications of lateral throat forms and the difference in the length of the
      lateral throat form between the dentures and the patient's actual anatomy. The
      classification of lateral throat form was determined by the patient's functional
      movements, and an implant depth gauge was used to measure the length of the
      lateral throat form in the patient's mouth and compare it to that of the
      dentures. One hundred mandibular edentulous patients were measured. The
      proportion of Neil's Class I lateral throat form was 70%, the proportion of Class
      II was 25%, and the proportion of Class III was 5%. The mean difference between
      the actual lateral throat forms and the dentures was 6.7 +/- 2.9 mm at the
      anterior point of measurement (from the anterior part of the retromolar pad to
      the mouth floor) and 10.0 +/- 3.7 mm at the posterior point (from the middle of
      the retromolar pad to the mouth floor). The difference in length between the
      ridge height of the mouth and the denture was statistically significant (P <
      .001).

PMID- 18069376
TI  - A 10-year longitudinal study of self-assessed chewing ability and dental status
      in 50-year-old subjects.
AB  - Chewing ability and dental status were assessed in 2 Swedish counties via
      questionnaires sent in 1992 and 2002 to all subjects born in 1942. Those who
      answered both questionnaires-at ages 50 and 60-were included in the study (n =
      5,008). The proportion of those who reported chewing ability as very good
      decreased from 75% to 66% during the 10-year follow-up. Approximately 80% of
      complete denture wearers considered their chewing ability to be good. Chewing
      ability was reported to be worse at age 60 than at age 50, although there was
      only a minor impairment in dental status.

PMID- 18069377
TI  - [Rapid viral response during treatment of chronic hepatitis B with pegylated
      interferon alfa-2a in children--preliminary report].
AB  - The aim of the study was to assess the viral response after 4 weeks of treatment
      with pegylated interferon alfa-2a chronic hepatitis B. Investigations were
      performed in 13 children in the age 11-17 years, with CHB, treated with PegIFN
      alfa-2a in the dose 100mcg/m2/week. After 4 weeks treatment statistically
      significant decrease of HBV viral load was observed. HBV DNA dissapearance was
      observed in 6/13 children with lower baseline ALT activity and lower HBV viral
      load before treatment. HBV DNA dissapearance was revealed in naive children with
      anti-HBe serum presence. During treatment no adverse events following dosis
      modifications were observed. Our preliminary observations of early HBV viral load
      supression seem to reveal that peginterferon alfa-2a may be benefit therapeutic
      option for children with CHB.

PMID- 18069378
TI  - [Long-term effects of HBV treatment Peg-IFN alfa-2a alone or combined with
      lamivudine].
AB  - The long-term outcomes showed a special place of IFN alfa-2a in therapy of
      chronic hepatitis B. Multivariate analysis revealed that patients who received 48
      weeks treatment PegIFN-alfa-2a with reduction of serum ALT level and suppression
      of HBV-DNA replication will have a chance to keep this effect in the future. The
      results of long term follow-up showed that IFN alfa-2a improves prognosis in
      terms of reduction of progression to cirrhosis and hepatocellular carcinoma.

PMID- 18069379
TI  - [Diagnostic and therapeutic aspects of hepatitis C virus induced thrombocytopenia
      (HCV-TP)].
AB  - Hepatitis C virus induced thrombocytopenia (HCV-TP) is a problematic disorder for
      diagnosis and treatment both for the infectious diseases specialists and
      hematologists. In the relation we decided to the present most up-to date views
      upon the HCV-TP patomechanism and systematized the diagnostic methods and
      therapeutic possibilities.

PMID- 18069380
TI  - [The modern therapy of lyme disease].
AB  - The modern therapy of Lyme disease, including newest Guidelines of the Infectious
      Diseases Society of America has been presented. Poland is endemic region for
      borreliosis and number of reported cases have been increasing rapidly. Newest
      guidelines should help doctors, not only infectious disease specialist, but
      especially General Practicioners, solve problems assiciated with therapy of Lyme
      disease.

PMID- 18069381
TI  - [Erysipelas--course of disease, recurrence, complications; a 10 years
      retrospective study].
AB  - OBJECT: we studied erysipelas by conducting a retrospective analysis of 319
      patients with erysipelas treated in Dermatology Department Jagiellonian
      University in Krakow between 1994 and 2004. METHODS: we performed a retrospective
      analysis of 319 patients hospitalized for erysipelas in our institution during a
      10 year period. The statistical significance was examined by chi square and
      Kruskal-Wallis test (significant value p< or =0.05). RESULTS: there were 35%
      males and 65% females patients. Median age was 63 years. Most of the female
      patients were pensioners (32.7%), most of the male patients were physical workers
      (40.5%). Summer time was the most frequent season for hospitalization (32.3%),
      and winter time was the rarest (17%). Most of the erysipelas has involved the
      lower limb (59.2%). There was significant dependence between the regional risk
      factors and occupation. The recurrent cases occurred in 67.3% cases with lower
      limb localisation in 69.44% cases. The most rare recurrent cases found on upper
      limb (6%). The systemic risk factors were associated with recurrent erysipelas in
      69.44%. Complications, such as abscess formation, lymphangitis, venous
      insufficiency, osteitis, arthritis, septic tendonitis and elephantiasis were
      found in 25%. CONCLUSIONS: after review of the literature and our experiences it
      is clear that there is a strong need for interdisciplinary treatment to avoid
      various potential complications of erysipelas.

PMID- 18069382
TI  - [Estimation of the frequency of occurrence of microorganisms isolated from blood
      cultures of hospitalized patients in the Hospital of Medical University in Gdansk
      in 2000-2002].
AB  - The aim of present study was retrospective analysis of the frequencies of
      occurrence of the most common microorganisms isolated from blood cultures in the
      Medical University in Gdansk from 2000 to 2002. The blood patterns were taken
      from adult patients with symptoms suggesting bacteriemia. During the 3 year study
      period 31788 blood samples were obtained, of which 5520 (17.37%) were positive.
      The number of Gram-positive bacteria isolated from blood increased and the rate
      of Gram-negative bacteria decreased over the study period. In addition the
      increase of frequency of Candida, VRE and Escherichia coli was noted. The number
      of infections caused by MRSA and Gram-negative ESbetaL+ diminished during time of
      observation. Acquaintance on the most frequently isolated organisms from blood
      patterns and they antimicrobial susceptibility should guide the choice of empiric
      antimicrobial regimens for patients with bacteriemia.

PMID- 18069383
TI  - [Norovirus infection in children hospitalized with acute gastroenteritis in
      northeastern Poland].
AB  - Noroviruses belonging to the family of Caliciviridae are a major cause of acute
      gastroenteritis in both children and adults. In the current study incidence of
      norovirus gastroenteritis was estimated in children hospitalized for acute
      gastroenteritis using commercially available ELISA tests. Epidemiological data
      were correlated with basic demographic findings. A hundred and forty nine
      children with acute gastroenteritis were enrolled in the study. Screening for
      common viruses causing gastroenteritis: rotavirus and adenovirus was performed
      and than stool samples were frozen and stored in <20 degrees C for future
      simultaneous testing with IDEIA Norovirus (Dakocytomation). Group I noroviruses
      were found in one child when 16 children were tested positive for Norowirus group
      two. In total noroviruses were found in 11.4% of children included in the study.
      Children with norovirus infection were 3 weeks to 15 years old (mean age 5.9
      years). Seasonal peak of norovirus infection was seen in September through
      December. The infectious agent has not been identified in 43% of investigated
      children. Our results support important role of noroviruses as a causing agent of
      gastroenteritis in children in Northeastern Poland. The importance of noroviruses
      may grow as rotavirus infections are likely to be eliminated due to wide
      introduction of vaccine in the nearest future. Routine testing for noroviruses
      should be considered in clinical practice.

PMID- 18069384
TI  - [Hantavirus specific IgG antibodies in population of zoologists and forest
      workers].
AB  - Serological diagnostic tests were introduced for detection of immunoresponse
      against to etiological agents of current infectious diseases. Interpretation
      criteria for those tests should eliminate unspecific reactions, cross-reactivity
      with related viruses as well as traces amounts of immunological response against
      to the past infections. In the case of past hantaviruses infections for obtaining
      an adequate seroepidemiological data revalidation of this tests are required. In
      present studies Puumala IgG results obtained in sera from healthy population had
      been analysed by statistical method and interpretation criteria were
      recalculated. Panels of 86 sera from forest workers and 47 zoologists working
      with small mammals were evaluated for hantavirus specific IgG (Hantavirus Puumala
      ELISA test). Puumala specific antibodies were detected in 7 zoologist's sera and
      in 5 sera gave equivocal results. All sera collected from forest's workers were
      negative. Statistical analysis based on negative results in forest workers group
      suggests that the cut off of the ELISA test suitable for diagnosis of suspected
      nephropathia epidemica cases is too restrictive for seroepidemiological research
      of hantavirus in healthy population.

PMID- 18069385
TI  - [The cross and unspecific reactions in serological examination for antibodies
      against hantavirus Puumala].
AB  - A serological survey of 78 zoologist capturing small wild rodents in their
      environment, 9 patients with suspected hantavirus infections and 21 patients with
      acute renal dysfunction for antibodies to hantaviruses was conducted in Poland.
      Survey was done by the indirect ELISA with Puumala and Hantaan virus antigens.
      Out of the 78 mammalogists 15 were seropositive for hantavirus Puumala IgG
      without history of clinical illness. Analysis of relation between reactive
      zoologist's sera IgG with antigens of Puumala and Hantaan viruses suggests that
      these persons had contact with Puumala/Tula viruses rather than with
      Dobrava/Saaremaa complex. Analysis of results of IgG and IgM presence by ELISA
      test have confirmed correct interpretation criteria proposed by manufacturer for
      serological diagnosis of suspected hantavirus infection. Both cross and
      unspecific reactions in the some sera have been observed. Low number of patients
      with suspected hantavirus infection suggests the existence of underestimation in
      registration of data collected in Poland and existence of non-diagnosed
      infections with hantaviring.

PMID- 18069387
TI  - [Botulism in the past and today--clinical aspects].
AB  - In this paper we review the most recent approach to clinical manifestations,
      diagnosis and treatment of botulism.

PMID- 18069386
TI  - [Occurrence of human hantavirus infections in Poland].
AB  - A spread of hantavirus infections causing hemorrhagic fever with renal syndrome
      is one of the rising epidemiological problems in the world. There is evidence
      that this type of viruses exists in almost all European countries. It is known
      that in Poland all the species of wild rodents hosting European hantaviruses are
      present. However, the data on hantavirus are very limited and information on
      incidence and prevalence of hantavirus infections among humans and animals in our
      country is lacking. Up to now, only one study in Poland has dealt with hantavirus
      infections in humans. Therefore the aim of the presented study was to show
      whether those infections are present in Poland and how prevalent they are. Two
      risk groups of hantavirus infection were investigated: group I--people with renal
      disorders (hospitalized patients with proteinuria and people suspected to
      hantavirus infection; n=30 people) and group II--healthy people employed at the
      universities, scientific institutions who due to their profession have contact
      with small rodents as well as students who captured those rodents when practicing
      or preparing their master theses (n=76) and forest workers (n=86). No one from
      the group of patients with renal disorders was positive for hantavirus Puumala
      IgG. Moreover, none of the forest workers had evidence of hantavirus infection.
      The hantavirus IgG were found only in the group of mammologists--19% persons were
      positive. Mammologists are an occupational subpopulation who remain in direct
      contact with host and/or with host excretions (virus is present in urine, feces,
      saliva of infected animals) and seem to be the most sensitive indicator of
      hantaviruses presence in environment. These results prove occurrence of
      hantavirus infections in Poland, however it seems that they are not very
      prevalent.

PMID- 18069388
TI  - [Botulism in the past and today--etiological, epidemiological and pathogenic
      aspects].
AB  - In this paper we review the most recent approach to etiology, epidemiology and
      pathogenesis of botulism.

PMID- 18069389
TI  - [The structure and mechanism of action of clostridial neurotoxins].
AB  - Clostridium botulinum and Clostridium tetani produce highly potent neurotoxins,
      called botulinum toxins and tetanus toxin, respectively. The clostridial
      neurotoxins specifically bind to neuronal cells and disrupt neurotransmisser
      release by cleaving proteins involved in specific vesicle membrane fusion. Each
      toxin is synthesized as an inactive approximately 150 kDa single-chain protein.
      The protein is posttranslationally proteolyzed to form the active dichain
      molecule in which the chains approximately 50 and approximately 100 kDa, remain
      linked by a disulfide bond. The structural organization is funcionally related to
      the fact that CNTs intoxicate neurons via four-step mechanism consisting of 1.
      binding, 2. internalization, 3. membrane translocation, and 4. enzymatic target
      modification. The L chain is responsible for the intracellular catalitic
      activity. The NH2-terminal 50-kDa domain of the H chain (HN) is implicated in
      membrane translocation, whereas the COOH-terminal part (HC) is mainly responsible
      for neurospecific binding.

PMID- 18069390
TI  - [AIDS associated cancers in the era of highly active antiretroviral therapy
      (HAART)].
AB  - HIV infected subjects are at increased risk of developing cancer and the risk
      seems to be directly associated with the level of immunodeficiency. Kaposi's
      sarcoma, Non-Hodgkin's lymphoma (ARL) and invasive cervical cancer are the most
      common AIDS-defining malignancies. HAART widely used since 1996 changed the
      natural process of HIV infection by aggressively suppressing viral replication
      and progress of HIV disease. It significantly reduced the incidence of AIDS
      associated events and deaths and even changed treatment regimens ofAIDS
      associated cancers. With the immune restoration afforded by HAART, patients
      better responded to cancer treatment. There are data demonstrating that HAART
      regimens alone lead to remission of Kaposi's sarcoma. HAART allows the use of
      standard-dose chemotherapies for NON-Hodgkin lymphoma in HIV infected pacients
      and same treatment regimen for invasive cervical cancer in infected patients as
      non-infected patients.

PMID- 18069391
TI  - [Chronic hepatitis C in patients with HIV/HCV coinfection with high CD4+
      lymphocytes count].
AB  - AIM: analysis of data characterizing HCV infection in patients infected with HIV.
      MATERIAL AND METHODS: 37 persons (29 male and 8 female) aged 23-49 years (mediana
      34), with HIV/HCV coinfection, treated (n=25) and untreated (n=12) with
      antiretroviral therapy. HAART was effective in treated patients; CD4+ count >350
      cells/microl. Viral load of HIV and HCV, HCV genotypes, CD4/CD8, biochemical
      tests, histopathological examination were measured. Results were analyzed
      statistically. RESULTS: the majority of patients were former IVDUs (n=31.84%), 3
      persons (8%)--MSM, 3 (8%)--route of infection unknown. Duration of HCV infection
      1-10 years, mediana 5. All patients were in A1 or A2 stage of HIV infection.
      Among patients treated with HAART (n=25) mediana of CD4+ count before treatment
      was 263 (69-595) cells/micro, mediana of HIV viral load 75000 copies/ml (n=7);
      2040-263414 copies/ml. 17 patients were currently treated with PI, 17 with NNRTI,
      and 2 patients with NRTI only. HCV genotype was determined in 32 patients: 3a-
      n=19 (59%), 1--n= 9 (28%) 4--n=4 (13%). HCV viral load: 2.4 x 10(5)-7.73 x 10(6)
      IU/ml, mediana 1.6 x 10(6). Levels of ALT: 21-358 IU/ml, mediana 102, AST: 20-195
      IU/ml, mediana 62, GGTP--9-463 IU/ml, mediana 58. ALT level was significantly
      higher in HCV genotype 3a infection (p=0.0214). Fibrosis stage above 2 was
      revealed in 3 patients and in majority (62%) was below 2. None patient had liver
      cirrhosis. Fibrosis was significantly higher in patients with low CD4+ nadir
      (p=0.03). CONCLUSIONS: Progression of liver fibrosis is slow in patients
      coinfected with HIV/HCV with high CD4+ count. High percentage of HCV genotype 3
      and mild fibrosis are good prognostic factors for effectiveness of HCV infection
      treatment in HIV infected persons.

PMID- 18069392
TI  - [Ocular manifestations during hepatitis C infection].
AB  - Hepatitis C wirus is one of the major blood-born pathogens of huge epidemic
      value. Due to its easy transmission, lack of routinely pursued tests and long non
      symptomatic period makes it crucial to be alert for all co-morbidites suggesting
      HCV infection. Consequently to reduce its farther transmission large knowledge of
      HCV should be spread as there is still no effective means of prophylaxis and its
      therapy is much costly. This article describes ophthalmic symptoms of hepatitis C
      virus infection such a mere keratoconiunctivitis sicca to ischemic retinopathy,
      macular edema and ischemic neuropathy.

PMID- 18069393
TI  - [Efficacy of combined antiviral therapy with interferon alfa and ribavirin in
      chronic hepatitis C patients with extrahepatic manifestations].
AB  - The aim of the study was to assess the efficacy and safety of treatment with
      interferon alpha and ribavirin in patients with chronic hepatitis C and
      extrahepatic manifestations as well as to determine prognostic factors of therapy
      effectiveness. 179 consecutive naive patients with chronic hepatitis C treated
      with interferon alpha and ribavirin were studied. 120 patients (67%) presented
      extrahepatic manifestations. The most frequent were cryoglobulinaemia,
      thrombocytopenia and thyroid gland pathology. Efficacy of antiviral treatment was
      lower (SVR 33.3% vs. 52.5%, p=0.013) and frequency of adverse events higher in
      patients with chronic hepatitis C and extrahepatic manifestations in comparison
      to those without extrahepatic pathology. Younger age, shorter duration of HCV
      infection and less advanced liver fibrosis were prognostic factors of better
      response to antiviral therapy in group of patients with chronic hepatitis C and
      extrahepatic manifestations.

PMID- 18069394
TI  - [Growth factors in chronic hepatitis C].
AB  - GROWTH FACTORS: HGF, PDGF, TNF-alpha, IL-6 have important role in liver
      regeneration. The aim of our study was the evaluation of serum growth factors
      concentration in chronic hepatitis C. Studied growth factors and cytokines levels
      were analyzed in relation to inflammatory and fibrotic changes in liver. MATERIAL
      AND METHODS: Seventy-five chronic hepatitis C patients were enrolled in this
      study. All patients had liver biopsy performed and the microscopic examination of
      liver tissues were analized according to Scheuer's classification. Serum
      concentrations of growth factors in patients' serum were assessed by use of ELISA
      method. The control group consisted of 20 healthy individuals. RESULTS AND
      CONCLUSIONS: Serum HGF, PDGF, TNF-alpha level showed significant elevation in the
      chronic hepatitis C compared to healthy controls. There was a statistically
      significant correlation between serum HGF and inflammatory activity and fibrosis
      stage. HGF seems to play an important function during chronic HCV infection.

PMID- 18069395
TI  - [Seasonal variation of hospital morbidity from asthma in Poland].
AB  - The aim of the paper was to describe and compare the seasonal hospital admissions
      among different subgroups of patients due to bronchial asthma with a special
      focus on demographic characteristic. Data were collected during the calendar year
      2003. Data were gathered for 32,933 patients from 522 hospitals across Poland
      with confirmed diagnosis of bronchial asthma or status asthmaticus. We noticed a
      distinct seasonal patterns in the number of hospitalizations due to asthma. Most
      cases clustered in the beginning and the end of the calendar year. Beside these
      hospitalization peaks, we observed a less pronounced increase of hospital
      admissions in spring and through summer months. It was most distinctly pronounced
      in children. It was also shown that gender of patients did not affect seasonal
      variability in our study. Emergency admissions to hospitals were less frequent in
      summer months, whereas elective admissions presented no such distinct pattern.
      The data revealed differences in seasonality in asthma hospital admissions in
      various age groups.

PMID- 18069396
TI  - [Preterm delivery in relation to combined pregnancy weight gain and prepregnancy
      body mass].
AB  - OBJECTIVE: To investigate association of preterm delivery with rate of pregnancy
      weight gain and prepregnancy body mass among polish women. MATERIALS AND METHODS:
      28,152 mothers from the 2001-2002 countrywide perinatal register. Delivery before
      37 weeks of gestation was considered as preterm. Relation between preterm
      delivery and body mass, rate of weight gain, maternal age, place of residence,
      marital status, education, parity, mode of delivery were examined in healthy
      women (without medical conditions potentially related to preterm delivery
      (18,891)). Association of preterm delivery with the factors was expressed as odds
      ratios (OR). Within group of vaginal delivery dependence of preterm delivery on
      rate of pregnancy weight gain and prepregnancy body mass was adjusted for above
      factors as potential confounders. RESULTS: In healthy vaginal delivering women
      odds ratios of preterm delivery adjusted for socio-economical potential
      confounders were computed: for low pregnancy weight gain and underweight OR=1.93
      (CI=1.7 ; 2.2), for low pregnancy weight gain and average-weight or overweight
      OR=1.15 (CI=1.1 ; 1,2), for average or high pregnancy weight gain and underweight
      OR =1.27 (CI =1.2 ; 1.4) (reference level: average-weight or overwaight and
      average or high pregnancy weight gain). CONCLUSIONS: Low rate of pregnancy weight
      gain and prepregnancy underweight increased risk of preterm delivery.

PMID- 18069397
TI  - [Assessment of Polish adolescents overweight and obesity using three different
      research tools].
AB  - The aim of this study was to determine the prevalence of overweight and obesity
      in Polish adolescents aged 13-15 years using three research tools: 1. BMI > or =
      85th (overweight) and BMI > or = 95th percentiles (obesity) using Polish national
      reference data, 2. WHO standard, 3. International Obesity Task Force (IOTF)
      standard. Height and weight were measured in randomly selected group of over 8000
      adolescents in 5 regions in Poland. The prevalence of overweight and obesity
      using these tools was similar--about 13%. The prevalence of obesity ranged from
      2.2 to 4.5%, depending on the methods used. We found underestimation for obesity
      especially in girls using international standards. WHO and IOTF standards are
      useful to estimate overweight and obesity to international comparisons. For
      national use: clinical and epidemiological Polish references data and definition
      BMI > or = 85th (overweight) and BMI > or = 95th percentiles (obesity) are better
      tools.

PMID- 18069398
TI  - [Dental state of 6 year old children in the region of Lodz for the year 2005].
AB  - An epidemiological study was carried out in the region of Lodz amongst 6-year old
      children which did not showed decrease in dental caries for the year 2005.
      OBJECTIVES: The purpose of the study was to evaluate the prevalence of carries,
      caries severity measured by the DMF index for secondary teeth and dmf index for
      primary teeth among 6-year old children in the region of Lodz for the year 2005.
      MATERIAL AND METHODS: 121 children aged 6 were randomly selected and examined, of
      which 60 children were from a town and 61 from a village respectively. The
      methodology was based on clinical examination according to WHO standards. The
      prevalence of carries, DMF and dmf index was calculated in the region of Lodz.
      RESULTS: The studies indicated that the prevalence of caries was 83.5% for 6-year
      old children in the region of Lodz. 16.5% children were caries free. Mean dmf in
      primary teeth was 5.37. No significant sex-dependent differences in the index
      values were found. DMF was 0.19 among 6-year-old children. There were significant
      sex- or localization-dependent differences in the index values. 83.5% 6-year-old
      children had permanent dentition. CONCLUSIONS: Intensity and prevalence of caries
      for 6 year old children in Lodz and surrounds is not satisfactory and the goal
      proposed by the WHO for 2010 for 6-year-old children will be not achieved in our
      region.

PMID- 18069400
TI  - [The culture of development].

PMID- 18069399
TI  - [Needs of schizophrenic's patients in perspective economical consequences of
      incapacity for work].
AB  - The main goal of the study was to analyze the indirect costs of schizophrenia.
      There was explained economic consequences of the disability and also the lost of
      the income of schizophrenia's patients. The aim of that research was to
      highlight: the social aspects of schizophrenia and the dyleme of the suitable for
      patients treatment and its indirect costs. In this research was proposed the
      variants for indirect costs analysis based on human capital approach. It was
      taken into account these problems linked to social costs assessment in
      psychiatry. It was introduced information's upon methods of costs estimation
      income lost in consequence diseases.

PMID- 18069401
TI  - [Physician-assisted suicide in university hospital: are we ready?].
AB  - Assisting people to commit suicide has generated a passionate public debate. In
      exceptional situations, access to this support can be granted to the demanders in
      a hospital environment. So did the CHUV and the academic hospitals of Geneva draw
      up a procedure permitting, in principle, the access to an assistance to commit
      suicide. Two recent clinical situations experienced in the CHUV's Service of
      internal medicine have created a lot of discussions, doubts and revealed,
      sometimes, divergent positions. By the light of this clinical cases, we wished to
      share the perspective of the internist in charge of the ethician, of the
      chaplain, of the medical director, of the psychiatrist and of the palliative care
      responsible. Theses complex situations illustrate the deep ambivalence felt by
      the clinicians confronted to situations which require a multidisciplinary
      approach.

PMID- 18069402
TI  - [Oral anticoagulation and the risk of major bleeding].
AB  - Oral anticoagulants are frequently used in clinical practice. The most important
      complication of oral anticoagulation is major bleeding. The incidence of major
      bleeding is about 2-3%/year in randomized controlled trials but may be
      considerably higher under real life conditions. Major bleeding risk in patients
      receiving oral anticoagulants depends on factors related to anticoagulation
      itself (intensity and quality), patient-related factors (demographic
      characteristics and comorbid diseases), and concomitant treatments with
      antiplatelet or non-steroidal anti-inflammatory drugs. The role of clinical
      prediction rules for major bleeding is discussed.

PMID- 18069403
TI  - [Hospital undernutrition: how not to ignore it any more?].
AB  - About 1/5 of patients are undernourished in Swiss hospitals. Despite of a high
      morbidity and mortality associated with this pathology, nearly 1/3 of them do not
      receive an appropriate nutritional support which can be even indicated at an
      obese patient. This paper approaches the key points of early nutritional care.
      NRS-2002 is presented like a simple tool able to identify patients nutritionally
      at-risk who are likely to benefit from nutritional support. Moreover, the major
      role of a diet adapted to the specific needs of the patient points out the need
      for an institutional policy coordinated around diet-nutrition.

PMID- 18069404
TI  - [Some less well known side effects of glucocorticoids: specific prevention and
      treatment?].
AB  - Steroid treatment is required in many clinical settings and if prolonged can be
      associated with serious side effects. Certain less well-known side effects may
      require specific prevention, diagnosis and treatment. The risk of developing
      hyperglycemia, psychiatric disorders and opportunistic infections associated with
      immunosuppression is often forgotten. We present herein some evidence on the
      prevalence, preventive measures and treatment of some of these side effects.
      Large controlled trials are lacking and do not allow to provide strong
      recommendations. Nevertheless, we try to provide some suggestions based on a
      review of the literature.

PMID- 18069405
TI  - [Complete bed rest prescription in an internal medicine ward: a dangerous
      treatment?].
AB  - A general knowledge led to the assumption that bed rest is beneficial for most
      illnesses and bed rest is prescribed in a large number of medical conditions.
      However, evidence from randomised studies and systematic reviews suggest a
      potentially harmful effect of bed rest. This review article discusses the utility
      of bed rest in some frequent medical pathologies such as myocardial infarction,
      pulmonary embolism, community acquired-pneumonia, and low back pain.

PMID- 18069406
TI  - [Fetal programming: an underestimated risk factor for cardiovascular and
      metabolic diseases].
AB  - Many epidemiological studies have shown a link between adverse events occuring
      during pregnancy and the development of cardiovascular and metabolic diseases
      later in life, a phenomenon called "fetal programming". The aim of this article
      is to summarize the knowledge in this field, and to present the main underlying
      mechanisms, among which epigenetics seems to play a determining role. This new
      knowledge might become particularly important for the practitioner and should
      prompt him to include an assessment of his patient's perinatal events in his
      daily practice, especially, in the light of the forthcoming availability of new
      drugs able to counteract the detrimental long term effects of such events.

PMID- 18069407
TI  - [Acute confusional episode--delirium in elderly patients. Definition, etiology
      and treatment].
AB  - Delirium, (acute confusional episode in European nomenclature) frequently occurs
      to elderly patients. This confusional condition is characterized by a sudden
      beginning and fluctuating clinical manifestations. It can bring out or showup a
      large number of illnesses. Generally transient and reversible, confusional state
      remains a medical emergency, motivating numerous consilium and psychiatric
      admissions. On the base of a case report, we aim to recall the high frequency of
      this affection in a somatic context and the importance of early diagnosis and
      treatment.

PMID- 18069408
TI  - [Bioterrorism: ideas of first resource medicine].

PMID- 18069409
TI  - [The medical profession].

PMID- 18069410
TI  - [Some actual images of our irrationality].

PMID- 18069411
TI  - [Malaria: a vaccine is not out of the question].

PMID- 18069412
TI  - [Thank you very much, James Watson!].

PMID- 18069413
TI  - [The impossibility of the egotist].

PMID- 18069414
TI  - Gastrointestinal sarcoidosis. A review.
AB  - BACKGROUND AND AIMS: Sarcoidosis is a multisystem granulomatous disorder. The
      gastrointestinal system is not commonly involved and is frequently asymptomatic.
      It can be associated with significant morbidity and indeed mortality. The aim of
      this article is to review the common and rare gastrointestinal and hepatobiliary
      manifestations of sarcoidosis. METHODS: All literature on gastrointestinal
      sarcoidosis was found using a computerized Pubmed search from 1966 to January
      2006. The keywords used were 'Gastrointestinal', 'Hepatobiliary', and
      'Sarcoidosis'. RESULTS: The article reviews each 'section' of the
      gastrointestinal and hepatobiliary tracts in turn, discusses difficulties in
      achieving a diagnosis, differential diagnoses and treatment options. CONCLUSIONS:
      This review highlights the difficulties in establishing a firm diagnosis of
      gastrointestinal sarcoidosis as it is frequently asymptomatic and can often mimic
      other non-caseating diseases. It also highlights some of the other disease
      associations such as with other biliary tract disorders and provides information
      on treatments, particularly the role of biologic therapies.

PMID- 18069415
TI  - Increased pulmonary neurotrophin protein expression in idiopathic interstitial
      pneumonias.
AB  - BACKGROUND AND AIM OF THE STUDY: Idiopathic interstitial pneumoniae (IIPs) are
      characterized by fibroblast proliferation, extracellular matrix deposition and
      progressive lung function impairment. Because effective therapeutic strategies
      still remain limited, research has been directed toward the identification of
      novel targets for additional therapeutic options. The neurotrophins (NTs) nerve
      growth factor (NGF), brain derived neurotrophic factor (BDNF) and NT-3, beside
      their importance in nervous, endocrine and immune system activities, participate
      in chronic inflammatory disorders and in repair processes. METHODS: We have
      investigated NT and high and low affinity NT receptor expression in IIPs using
      immunoblots and immunohistochemistry. Fourteen idiopatic pulmonary fibrosis/usual
      interstitial pneumoniae (IPF/UIP), eight non specific pneumoniae (NSIP) and eight
      respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) were
      analyzed. RESULTS: Immunoblots revealed that NT and high affinity NT receptor
      proteins were more abundantly expressed in IPF/UIP than NSIP and RB-ILD patients.
      In RB-ILD, a faint expression of NT-3 and NT receptors were detected. NT and NT
      receptor immunostaining was detected in interstitial cells from IPF/UIP, NSIP and
      RB-ILD patients by immunohistochemistry. Fibroblastic foci in IPF/UIP strongly
      stained for BDNF and its high affinity receptor TrkB and in lesser amount for
      NGF, NT-3 and their respective high affinity receptors TrkA and TrkC.
      Furthermore, in fibroblast culture derived from IPF/UIP patients, the
      proliferation rate of primary culture and clones derived from primary lines was
      stimulated by BDNF but down regulated by NT-3. In contrast, NGF did not influence
      IPF/UIP fibroblasts proliferation. CONCLUSIONS: Our data suggest that that NTs
      may exert differential activities on lung fibroblasts and may be considered as
      potential regulatory molecules influencing fibroblast behavior in IPF/UIP
      patients. Therefore, NTs may play a role in IIPs patho-physiology representing
      novel potential therapeutic targets.

PMID- 18069416
TI  - A quantitative proteomic analysis of soluble bronchoalveolar fluid proteins from
      patients with sarcoidosis and chronic beryllium disease.
AB  - BACKGROUND: Sarcoidosis and chronic beryllium disease (CBD) are granulomatous
      disorders which can lead to development of chronic inflammation and fibrosis.
      These diseases have several similarities from their clinical aspects. The aim of
      this study was to compare the protein profile at the site of active inflammation
      i.e. the lungs of patients with sarcoidosis and CBD. METHODS: Bronchoalveolar
      lavage (BAL) proteins from patients having sarcoidosis or CBD were studied using
      two dimensional gel based proteomics. In this study, we used Difference Gel
      Electrophoresis (DIGE) proteomics approach to analyse the protein expression
      profiles from sarcoidosis patients (n=4), CBD (n=4) and healthy controls (n = 5).
      Subsequently, differentially expressed proteins were identified by using mass
      spectrometry. RESULTS: We found 37 protein-spots with statistically different
      expression levels, and identified 14 of these proteins. The protein expression
      levels of peroxiredoxin 5, heat shock protein 70, complement C3, annexin A2 and
      transthyretin were significantly different in sarcoidosis versus control group.
      The proteins; hemopexin, beta2-microglobulin, alpha-1 antitrypsin, cystatin B,
      IgG kappa chain, apolipoprotein A1, and albumin were significantly different
      between CBD versus control group. When comparing CBD versus sarcoidosis, we found
      superoxide dismutase and hemoglobin upregulated in the CBD group. CONCLUSION: By
      using quantitative proteomics, we were able to find proteins with different
      expression levels in both diseases.

PMID- 18069417
TI  - The MCP-1-2518 (A to G) single nucleotide polymorphism in Czech patients with
      pulmonary sarcoidosis: association with Lofgren's syndrome.
AB  - BACKGROUND AND AIM: The chemokine Monocyte Chemoattractant Protein (MCP)-1/CCL2,
      a chemoattractant for mononuclear cells, has already been implicated in the
      pathogenesis of sarcoidosis. A single nucleotide polymorphism (SNP) located at
      the position -2518 (A to G) of the MCP-1 gene has been reported to alter
      production of the MCP-1 protein in vitro and ex vivo. The present study,
      therefore, explored a possible association between MCP-1-2518 SNP and pulmonary
      sarcoidosis including its clinical subtypes, especially Lofgren's syndrome (LS).
      Relationship between MCP-1-2518 SNP and serum MCP-1 levels was also investigated.
      METHODS: MCP-1-2518 genotypes were determined using PCR with sequence specific
      primers in 105 sarcoidosis patients and 359 healthy control subjects. The
      differences in genotype and allelic frequencies between the patient and control
      groups were assessed by chi2 test. MCP-1 protein concentrations in serum samples
      from 77 sarcoidosis patients were determined by ELISA; Mann-Whitney U-test was
      used to test for differences in protein levels. RESULTS: While there was no
      significant difference in distribution of MCP-1-2518 alleles between sarcoidosis
      patients and healthy control subjects, a significantly higher proportion of the
      MCP-1-2518*G allele (p = 0.01, odds ratio (OR) = 2.3) and of the GG genotype (p =
      0.03, OR = 3.9) was observed in the patients with LS compared to control
      subjects. There was also a significantly higher frequency of the MCP-1-2518*G
      allele in patients presenting with LS compared to the patients without LS (p =
      0.04, OR = 2.1). MCP-1 protein in serum was not related to MCP-1-2518 gene
      variants. CONCLUSION: A possible interpretation of our results is, that the MCP-1
      2518 SNP or a gene located nearby may modify clinical manifestation of
      sarcoidosis towards Lofgren's syndrome. Future investigations in other
      population(s) should, therefore, follow this case-control study.

PMID- 18069418
TI  - Efficacy of hormonal manipulation in lymphangioleiomyomatosis. A 20-year
      experience in 36 patients.
AB  - RATIONALE: Lymphangioleiomyomatosis (LAM) is a rare disease of unknown aetiology
      which mainly affects women of reproductive age. A growing body of evidence
      suggests a relation between the disease and estrogenic hormones. In particular,
      pregnancy and use of estrogens favour the progression of the disease, which is in
      turn slowed down by menopause. These observations suggested already in the past a
      treatment strategy based on hormonal manipulation: discontinuation of estrogens
      containing medications, avoiding pregnancy, inhibition of estrogens activity and
      induction of menopause. OBJECTIVES: In the present study, conducted on a
      relatively large population for a rare disease, we sought to show the hormonal
      manipulation's positive effects for the survival rate. METHODS: 36 women
      suffering from LAM were evaluated between January 1985 and March 2005. All our
      patients were treated with hormonal therapy, following different schemes. The
      response to the treatment was evaluated in all patients with arterial blood
      sampling, lung function tests (total body plethysmography, DLCO), measurement of
      the hormones in the blood, chest and abdomen CT scan. MEASUREMENTS AND MAIN
      RESULTS: The survival rate since the clinical onset was 97% at the 5 year
      timepoint, 90% at 10 years, and 71% at 25 years. Previous studies, conducted
      before the introduction of the hormonal treatment showed a survival rate of 20%
      at 10 years. CONCLUSIONS: Our results highlight the role of the hormonal
      manipulation as a mainstay in the treatment of LAM, with the capability of
      reducing mortality and improving the quality of life as well.

PMID- 18069419
TI  - Bone turnover and hip bone mineral density in patients with sarcoidosis.
AB  - BACKGROUND AND AIM OF THE WORK: Sarcoidosis is a chronic inflammatory T-cell
      driven disease that can also affect bone. We evaluated bone remodelling and bone
      mineral density (BMD) in patients with sarcoidosis and their dependency of
      disease-related and treatment-related factors. METHODS: In 124 patients BMD of
      the hip (DXA) and markers of bone resorption (ICTP) and formation (PINP) were
      evaluated. Furthermore a lateral DXA of the spine for morphometric assessment of
      vertebral deformities was performed in 87 patients. Potential predictors of bone
      markers, BMD and determinants of prevalent vertebral deformities were assessed
      using multiple and logistic regression analysis. RESULTS: The population studied
      comprised untreated patients (n=51), patients that previously used
      glucocorticoids (n=31) and patients currently using glucocorticoids (n=42). In
      all these groups the age- and gender corrected Z-scores of the hip were normal,
      except in untreated patients, which revealed an increased Z-score at the
      trochanter (p = 0.004). In all but the patients currently on glucocorticoids the
      Z-scores for PINP and ICTP were increased (p < 0.05). In patients currently on
      glucocorticoids the Z-ICTP was also increased (p < 0.05), but the Z-PINP
      decreased (p < 0.01 compared to untreated patients). In 20.6% of patients one or
      more morphometric vertebral deformities were found. CONCLUSIONS: Hip BMD is
      normal in patients with sarcoidosis, despite an increased bone turnover. This may
      imply that in sarcoidosis mechanisms are involved that compensate for the well
      known effects of cytokines in inflammatory diseases on osteoclastogenesis and
      bone resorption. Nonetheless, vertebral deformities suggestive of fracture were
      found in a significant number of patients which indicates that patients with
      sarcoidosis still have a relevant fracture risk.

PMID- 18069420
TI  - Chitotriosidase analysis in bronchoalveolar lavage of patients with sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a systemic granulomatous disease characterised by T
      helper cell/macrophage alveolitis. Activated macrophages release mediators, such
      as cytokines, chemokines, oxygen radicals, and enzymes. In a previous paper we
      found higher levels of chitotriosidase, a macrophage derived enzyme, in serum of
      patients with sarcoidosis than in controls. Serum chitotriosidase levels were
      correlated with sarcoidosis radiological stages. Human chitotriosidase is
      involved in the pathogenesis of many lysosomal storage disorders and is
      selectively expressed in chronically activated tissue macrophages. METHODS: In
      the present study we determined chitotriosidase concentrations in bronchoalveolar
      lavage of patients with newly diagnosed pulmonary sarcoidosis (divided into two
      groups according to clinical parameters) and of controls with an ELISA test.
      RESULTS: Significantly different chitotriosidase concentrations were found in BAL
      of patients than controls, especially in patients with progressing disease.
      CONCLUSION: Chitotriosidase but not angiotensin converting enzyme concentrations
      correlated with sarcoidosis radiological stages, and also with the degree of lung
      infiltrate seen by CT-scan, suggesting that the former enzyme (detected locally
      and sistemically) may play a role in the pathogenesis of the disease. Further
      studies with a greater number of patients are needed to confirm this hypothesis
      and to determine whether chitotriosidase may be a marker of the severity of
      sarcoidosis.

PMID- 18069421
TI  - Measurement of exhaled nitric oxide in healthy adults.
AB  - BACKGROUND AND AIM: Measurement of exhaled nitric oxide (NO) is useful in the
      diagnosis and management of asthma. The aims of this study were to investigate
      the effects of physiologic confounders on levels of fractional exhaled NO
      (FE(NO)) in healthy adults and to establish reference values of FE(NO) measured
      according to American Thoracic Society (ATS) guidelines. METHODS: FE(NO) was
      measured in 122 healthy nonsmoking subjects of 20 to 65 years with a
      chemiluminescence analyser using the single breath online technique and an
      exhalation flow of 50 mL/s. RESULTS: The geometric mean [SE] FE(NO) was
      21.6[1.06] ppb in males and 16.3[1.07] ppb in females (p < 0.01). FE(NO)
      increased significantly with body size and spirometric indices. In a stepwise
      regression analysis, body weight was the only variable included in the model (r =
      0.36, p < 0.0001) and explained gender differences in FE(NO). When weight-related
      variables, including BMI, BSA and dead space volume, were analysed in a stepwise
      regression model, dead space volume gave the best correlation with FE(NO) (R =
      0.39; p < 0.0001). CONCLUSION: The present study estimated that mean FE(NO) in
      healthy Caucasian subjects of 20 to 65 years, measured according to ATS
      guidelines with the online single breath technique, ranges from 15 to 24 ppb
      depending on the body weight. We suggest that the volume of dead space may
      explain the effect of weight on exhaled NO. However, a substantial part of FE(NO)
      variability in normal subjects remains unexplained.

PMID- 18069422
TI  - Oxygen desaturation during a 4-minute step test: predicting survival in
      idiopathic pulmonary fibrosis.
AB  - BACKGROUND AND AIM: PaO2 during exertion is a significant predictor of IPF
      survival. The aim of study was to assess oxygen desaturation for predicting
      survival in IPF patients at the end of a 4-minute step test. METHODS: A
      longitudinal study was done in 59 patients with IPF from February 1998 to January
      2005. Upon initial examination, lung function testing was performed, as were 4
      minute step tests, in which patients stepped up and down on a 20-cm single step
      at a self-paced rate. In the final minute, oxygen saturation by pulse oximetry
      (SpO2) was measured. RESULTS: Median survival was 58 months. SpO2 at rest and
      during stepping, dyspnea score, as well as FVC% and DLCO% were found to be
      significant predictors of mortality. Desaturation to 89% or less,correlated with
      a hazard ratio of 2.39 for IPF mortality (95% CI, 1.16-3.63; p < 0.0001). In
      patients with such desaturation, four-year survival was 39%, compared to 96% in
      those with no desaturation. In a multivariate Cox analysis, only SpO2 during
      stepping remained significant (p < 0.0001). A DLco < 45% of predicted (n=40
      patients) correlated with a hazard ratio of 2.23 for mortality (95% CI, 0.73
      3.71; p < 0.0001). When the analysis was repeated including DLco, SpO2 and DLco
      remained significant (p < 0.05). CONCLUSION: Desaturation to 89% or less in a 4
      min step test is a strong predictor of mortality in IPF patients.

PMID- 18069423
TI  - A requirement for histologic confirmation of stage I sarcoidosis is far more
      likely to prove harmful than helpful.

PMID- 18069424
TI  - Acute fibrinous and organizing pneumonia in a patient with collagen vascular
      disease "stigma".

PMID- 18069425
TI  - The impact of poverty in high-risk neonatal care.

PMID- 18069426
TI  - Neonatal mortality: a critical global health issue.

PMID- 18069427
TI  - Poverty as context for the parenting experience of low-income Lumbee Indian
      mothers with a medically fragile infant.
AB  - PURPOSE: To explore the influence of poverty on the parenting experience and
      maternal developmental trajectory of Lumbee mothers with medically fragile
      infants. DESIGN: A multiple-case study design using secondary data from a larger
      longitudinal study of parental role attainment with medically fragile infants.
      SAMPLE: Five cases involving mothers who were Lumbee Indians and who had
      medically fragile infants. RESULTS: The key features of the mothers' talk about
      their parenting experiences were organized into categories that fit into five
      inductively derived themes related to poverty. IMPLICATIONS: Health care
      professionals need to be aware of how the context of living in poverty affects
      mothers of high-risk infants who are hospitalized in tertiary care units. In
      particular, low-income mothers, especially American Indians living in high
      poverty areas, urgently need improved community resources such as access to birth
      control; early prenatal care; programs to help reduce drug, alcohol, and tobacco
      use both during and following pregnancy; and follow-up health and developmental
      services for their infants.

PMID- 18069429
TI  - Peripheral intravenous extravasation: nursing procedure for initial treatment.
AB  - Tissue extravasation resulting from intravenous (IV) infiltration can occur as a
      complication of neonatal intensive care with varying degrees of morbidity.
      Serious extravasation can result in pain, infection, disfigurement, prolonged
      hospitalization, increased hospital costs, and possible litigation. Although most
      infiltrates resolve spontaneously after the IV catheter is removed, IV
      extravasations and tissue sloughing do occur in NICU patients. Specific therapies
      are based on assessment of the degree of the injury. The goal in managing tissue
      damage after IV extravasation is to improve tissue perfusion and prevent
      progression of tissue necrosis. This article presents an initial approach to
      nursing care for peripheral IV infiltrations to guide clinicians in management of
      this complication. The approach is based on clinical experience, descriptive
      studies, and reports from expert committees.

PMID- 18069428
TI  - Retinopathy of prematurity: the disease process, classifications, screening,
      treatment, and outcomes.
AB  - Retinopathy of prematurity (ROP) is the cessation of normal eye development and
      subsequent abnormal vessel growth that occurs exclusively in premature infants.
      ROP was first discovered in the 1940s and was for two decades the leading cause
      of blindness in children. Currently, the disease causes about 500 new cases of
      blindness per year. The severity of the disease increases with decreasing
      gestational age. The pathogenesis of ROP involves disruption of normal retinal
      vascularization. Vessel endothelial growth factor, insulin-like growth factor,
      and oxygen play important roles in its development. ROP is classified using an
      international classification system that provides direction for screening and
      treatment of premature infants. Examinations are performed by ophthalmologists,
      who identify the scope of vascularization, the degree of abnormal vessel growth,
      and the amount of the eye that is affected. Treatment modalities include
      cryosurgery and laser photocoagulation. Long-term outcomes include both
      structural and functional vision problems.

PMID- 18069430
TI  - An evidence-based review of hyperbilirubinemia in the late preterm infant, with
      implications for practice: management, follow-up, and breastfeeding support.
AB  - As the incidence of late preterm births continues to rise, health care providers
      need to be aware of this population's unique needs. This review focuses on the
      additional risks late preterm infants encounter related to unconjugated
      hyperbilirubinemia and the importance of breastfeeding support and follow-up.
      Additional, population-based studies concentrating on the late preterm infant are
      needed to determine more clearly the incidence of hyperbilirubinemia, with
      specific levels documented; incidence of ED visits and rehospitalizations related
      to hyperbilirubinemia; and incidence of bilirubin neurotoxicity with both short-
      and long-term follow-up. It is also important to study these outcomes in relation
      to the nature and degree of risk associated with early discharge, insufficient
      follow-up, and breastfeeding. Future research is needed to develop evidence-based
      recommendations for optimal discharge timing, counseling, and postdischarge
      follow-up of late preterm infants, particularly those who are breastfed, to
      promote safe patient care.

PMID- 18069431
TI  - Designing medication safety in the NICU.

PMID- 18069432
TI  - Is anybody listening?

PMID- 18069433
TI  - End-of-Life Care for Seniors: contributions from a New Emerging Team.

PMID- 18069434
TI  - Self-perceived burden to others: patient and family caregiver correlates.
AB  - AIMS: To provide further evidence about the prevalence and correlates of the
      sense of "self-perceived burden" (SPB) to others, and to examine its association
      with caregiver reports of burden. METHODS: The participants were 65 patients with
      advanced cancer and their family caregivers. Patients completed measures of SPB
      and family members completed a caregiver burden scale. RESULTS: SPB was
      experienced at minimal to mild levels by 35% of patients, and at moderate to
      extreme levels by another 28%. It was correlated with some physical symptoms, but
      more frequently with psychological symptoms. The family members of patients who
      reported that SPB was a significant problem had higher scores on the caregiver
      burden scale than family members of other patients (p=0.048), although the
      overall correlation was modest. CONCLUSIONS: SPB is a common and distressing
      concern for many patients receiving palliative care and is associated with a
      number of other distressing concerns.

PMID- 18069435
TI  - Developing rural communities' capacity for palliative care: a conceptual model.
AB  - The population in Canada and other developing countries is aging, increasing the
      need for palliative care services. In rural communities, care of dying people is
      normally provided by health care professionals as part of a generalist practice,
      not by palliative care specialists. Despite a lack of specialists and resources,
      some rural communities have developed local palliative care programs. The goal of
      this research was to conceptualize rural communities' process of developing
      palliative care programs using a theoretical perspective of community capacity
      development. Data were from nine focus groups of interdisciplinary rural health
      care providers who provided palliative care in seven provinces/territories of
      Canada. The outcome is a theoretical model that conceptualizes the process of
      developing palliative care programs in four sequential phases: antecedent
      community conditions, a catalyst, creating the team, and growing the program. The
      activities of each phase are outlined. This research offers practical and
      theoretical knowledge to guide practitioners and planners seeking to develop
      palliative care programs in other rural communities.

PMID- 18069436
TI  - Development of a palliative care education program in rural long-term care
      facilities.
AB  - In North America, people 85 years and older are the fastest growing age cohort
      and long-term care homes are increasingly becoming the place of end-of-life care.
      This is especially true in rural communities where services are lacking. Staff in
      long-term care homes lack education about palliative care, but in rural areas,
      accessing education and the lack of relevant curricula are barriers. The focus of
      this paper is to describe an approach to developing and delivering a research
      based palliative care education curriculum in rural long-term care homes. The
      approach included conducting a detailed assessment of staffs' educational needs
      and preferred educational formats; developing a 15-hour interprofessional
      curriculum tailored to the identified needs; and delivering the curriculum on
      site in rural long-term care homes. Staff confidence and participation in
      delivering palliative care increased. Based on work in northwestern Ontario,
      Canada, this approach can serve as a model for palliative care education in other
      rural areas.

PMID- 18069437
TI  - So no one dies alone: a study of hospice volunteering with rural seniors.
AB  - This paper summarizes the results of a qualitative study of hospice volunteering
      in the rural communities of northwestern Ontario. In this region, there are 13
      independent and active hospice volunteer programs serving communities ranging in
      population from 1,000 to 15,000. The 13 volunteer coordinators in these
      communities participated in a phone interview in which they described the role of
      hospice volunteers in their community and the kinds of clients they serve. The
      results indicate that the hospice volunteers in this rural region spend a large
      part of their time visiting medically frail and lonely seniors who are at risk of
      dying alone or without adequate care and companionship at the end of life. Long
      term visiting to build relationships of trust and genuine caring are considered
      the ideal in these communities. Implications for end-of-life care for rural
      seniors are discussed.

PMID- 18069438
TI  - Nurses' perceptions around providing palliative care for long-term care residents
      with dementia.
AB  - Providing palliative care for residents with dementia in long-term care (LTC)
      settings is problematic due to their declining verbal abilities and related
      challenges. The goal of this study was to explore nurses' perceptions around
      providing palliative care for such residents. Using a qualitative descriptive
      design, data were gathered from focus groups at three LTC facilities.
      Participants represented all levels of nursing staff. Concepts that emerged from
      the data were labelled, categorized, and coded in an iterative manner. Nurses
      appraise residents' general deterioration as a main factor in deciding that a
      resident is palliative. Nurses often employ creative strategies using limited
      resources to facilitate care, but are challenged by environmental restrictions
      and insufficient educational preparation. However, nurses said they do not wish
      for residents to be transferred to a hospice setting, as they wish to grieve with
      residents and their family members. Nurses aim to facilitate a "good death" for
      residents with dementia, while trying to manage multiple demands and deal with
      environmental issues. Supportive and educational initiatives are needed for
      nursing staff and families of dying residents.

PMID- 18069439
TI  - Palliative care becomes 'uninformed euthanasia' when patients are not offered
      noninvasive life preserving options.

PMID- 18069440
TI  - The use of subcutaneous drainage for the management of lower extremity edema in
      cancer patients.

PMID- 18069441
TI  - The broader implications of managing statins at the end of life.

PMID- 18069442
TI  - Competitive bidding--the continuing saga.

PMID- 18069443
TI  - The doctorate in clinical laboratory science: a projection of professional
      outcomes.

PMID- 18069444
TI  - The rural rotation in a medical technology program: a ten-year retrospective
      study.
AB  - OBJECTIVE: This study evaluated the effectiveness of a rural rotation as a tool
      to recruit medical technology program graduates to medically underserved areas.
      DESIGN: A paper survey was distributed to all 1994 - 2003 graduates of the West
      Virginia University Medical Technology Program. SETTING: The survey was mailed to
      the graduates' homes. PATIENTS OR OTHER PARTICIPANTS: Ninety-four of the two
      hundred six surveys were returned for a response rate of 45.6%. INTERVENTIONS:
      Surveys were mailed in January 2004. MAIN OUTCOME MEASURES: Responses to
      questions regarding choice of site for rural rotation, whether or not a job was
      offered at the rural site, and whether the graduate subsequently worked at a
      rural site were tabulated. Responses to questions concerning whether the rotation
      helped the respondent to appreciate the needs of rural health facilities and
      whether the rotation resulted in a greater interest in working in a rural area
      were tabulated. Responses were also tabulated for questions about the value of
      the rural rotation to the respondent's education and whether the rural rotation
      was recommended for future students. RESULTS: Of respondents, 70.2% chose their
      rural rotation sites due to proximity to their homes and 38.3% were offered jobs
      at their rural rotation sites. 50% of all respondents subsequently worked at a
      rural site. Of respondents, 73.4% indicated strong agreement that the rotation
      helped them appreciate the needs of the rural facility, and 37.2% indicated
      agreement with becoming more interested in working at a rural site. Of
      respondents, 65% indicated that the rural rotation was beneficial and that they
      would recommend it to future students. CONCLUSION: Results of the survey suggest
      that a prior rural affinity is a factor associated with selection of rural sites
      for medical technology program graduates. The survey results also suggest that a
      rural rotation during medical technology education is beneficial to individuals,
      including those who elect not to go to rural sites after graduation.
      ABBREVIATIONS: Health professions shortage areas (HPSAs) nurse practitioners (NP)
      medically underserved areas (MUAs) West Virginia Rural Health Education
      Partnerships (WVRHEP).

PMID- 18069445
TI  - Three alternative structural configurations for phlebotomy: a comparison of
      effectiveness.
AB  - OBJECTIVE: This study was designed to compare the effectiveness of three
      alternative structural configurations for inpatient phlebotomy. It was
      hypothesized that decentralized was less effective when compared to centralized
      inpatient phlebotomy. DESIGN: A non-experimental prospective survey design was
      conducted at the institution level. Laboratory managers completed an
      organizational survey and collected data on inpatient blood specimens during a 30
      day data collection period. SETTING/PARTICIPANTS: A random sample (n=31) of
      hospitals with onsite laboratories in the United States was selected from a
      database purchased from the Joint Commission on Accreditations of Healthcare
      Organizations (JCAHO). MAIN OUTCOME MEASURE: Effectiveness of the blood
      collection process was measured by the percentage of specimens rejected during
      the data collection period. RESULTS: Analysis of variance showed a statistically
      significant difference in the percentage of specimens rejected for centralized,
      hybrid, and decentralized phlebotomy configurations [F (2, 28) = 4.27, p = .02]
      with an effect size of .23. Post-hoc comparison using Tukey's HSD indicated that
      mean percentage of specimens rejected for centralized phlebotomy (M = .045, SD =
      0.36) was significantly different from the decentralized configuration (M = 1.42,
      SD = 0.92, p = .03). found to be more effective when compared to the
      decentralized configuration.

PMID- 18069446
TI  - Thrombotic microangiopathy (TTP and HUS): advances in differentiation and
      diagnosis.
AB  - Detection of the proteolytic enzyme ADAMTS-13 may be used to differentiate
      between the forms of thrombotic microangiopathy (TMA), thrombotic
      thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS).

PMID- 18069447
TI  - Is there a genetic relationship between arterial and venous thrombosis?

PMID- 18069448
TI  - Cross talk between the inflammation and coagulation systems.

PMID- 18069449
TI  - Introduction to proteomics.
AB  - Technological advances in the field of genomics have given rise to the
      development of a new area called proteomics. Proteomics involves the analysis of
      all proteins expressed in a genome and uses a combination of sophisticated
      technologies such as two-dimensional electrophoresis, mass spectrometry and
      bioinformatics to identify and characterize proteins. This new area offers the
      potential to discover new biomarkers, improve diagnosis, and improve the
      prognosis of disease processes. This article presents an overview of proteomics
      importance and related technologies.

PMID- 18069450
TI  - Proteomics technology.
AB  - Proteomics techniques are essential tools for protein detection and
      characterization. Besides several advances in the proteomics field, the two
      dimensional electrophoresis (2-DE) technique is the most important method for
      protein separation. The combination of 2-DE technique, new advances in mass
      spectrometry and bioinformatics promises to unveil protein function and
      pathological mechanisms of disease.

PMID- 18069451
TI  - Proteomics: clinical applications.
AB  - The word proteomics was coined in 1997 to describe the changes in all proteins
      expressed by a genome. Several sophisticated techniques including two-dimensional
      electrophoresis, imaging, mass spectrometry, and bioinformatics are used in
      proteomics to identify, quantify, and characterize proteins. Clinical proteomics
      is the application ofproteomics techniques to the medical field. The main aim of
      this methodology is to identify proteins involved in pathological processes and
      to understand how illness can lead to altered protein expression. Clinical
      proteomics offers the opportunity and the potential to develop new diagnostic and
      prognostic tests, to identify new therapeutic targets, and eventually to allow
      the design of individualized patient treatment. Here we present an overview of
      proteomics applications to the study of disease and its potential to improve
      diagnosis and prognosis.

PMID- 18069452
TI  - A method of assessing air toxics concentrations in urban areas using mobile
      platform measurements.
AB  - The objective of this paper is to demonstrate an approach to characterize the
      spatial variability in ambient air concentrations using mobile platform
      measurements. This approach may be useful for air toxics assessments in
      Environmental Justice applications, epidemiological studies, and environmental
      health risk assessments. In this study, we developed and applied a method to
      characterize air toxics concentrations in urban areas using results of the
      recently conducted field study in Wilmington, DE. Mobile measurements were
      collected over a 4- x 4-km area of downtown Wilmington for three components:
      formaldehyde (representative of volatile organic compounds and also
      photochemically reactive pollutants), aerosol size distribution (representing
      fine particulate matter), and water-soluble hexavalent chromium (representative
      of toxic metals). These measurements were,used to construct spatial and temporal
      distributions of air toxics in the area that show a very strong temporal
      variability, both diurnally and seasonally. An analysis of spatial variability
      indicates that all pollutants varied significantly by location, which suggests
      potential impact of local sources. From the comparison with measurements at the
      central monitoring site, we conclude that formaldehyde and fine particulates show
      a positive correlation with temperature, which could also be the reason that
      photochemically generated formaldehyde and fine particulates over the study area
      correlate well with the fine particulate matter measured at the central site.

PMID- 18069453
TI  - Which meteorological conditions produce worst-case odors from area sources?
AB  - Two competing meteorological factors influence atmospheric concentrations of
      pollutants from open liquid area sources such as wastewater treatment plant
      units: temperature and stability. High temperatures in summer produce greater
      emissions from liquid area sources because of increased compound volatility;
      however, these emissions tend to disperse more readily because of frequent
      occurrence of unstable conditions. An opposite scenario occurs in winter, with
      lesser emissions due to lower temperatures, but also frequently less dispersion,
      due to stable atmospheric conditions. The primary objective of this modeling
      study was thus to determine whether higher atmospheric concentrations from open
      liquid area sources occur more frequently in summer, when emissions are greater
      but so is dispersion, or in winter, when emissions are lesser but so is
      dispersion. The study utilized a rectangular clarifier emitting hydrogen sulfide
      as a sample open liquid area source. Dispersion modeling runs were conducted
      using ISCST3 and AERMOD, encompassing 5 yr of hourly meteorological data divided
      by season. Emission rates were varied hourly on the basis of a curve-fit
      developed from previously collected field data. Model output for each season was
      used to determine (1) maximum 2-min average concentrations, (2) the number of
      odor events (2-min average concentrations greater than odor detection
      thresholds), and (3) areas of impact. On the basis of these 3 types of output, it
      was found that the worst-case odors were associated with summer, considering
      impacts of meteorology upon both emissions and dispersion. Not accounting for the
      impact of meteorology on emissions (using a constant worst-case emission rate)
      caused concentrations to be overpredicted compared with a variable emission rate
      case. The highest concentrations occurred during stability classes D, E, and F,
      as anticipated. A comparison of ISCST3 and AERMOD found that for the area source
      modeled, ISCST3 predicted higher concentrations and more odor events for all
      seasons.

PMID- 18069454
TI  - Compilation and assessment of recent positive matrix factorization and UNMIX
      receptor model studies on fine particulate matter source apportionment for the
      eastern United States.
AB  - In 1997, the U.S. Environmental Protection Agency (EPA) revised its particulate
      matter standards to include an annual standard for fine particulate matter
      (PM2.5; 15 microg/m3) and a 24-hr standard (65 microg/m3). The 24-hr standard was
      lowered to 35 microg/m3 in 2006 in an effort to further reduce overall ambient
      PM2.5 concentrations. Identifying and quantifying sources of particulate matter
      affecting a particular location through source apportionment methods is now an
      important component of the information available to decision makers when
      evaluating the new standards. This literature compilation summarizes a subset of
      the source apportionment research and general findings on fine particulate matter
      in the eastern half of the United States using Positive Matrix Factorization. The
      results between studies are generally comparable when comparable datasets are
      used; however, methodologies vary considerably. Commonly identified source
      categories include: secondary sulfate/coal burning (sometimes over 50% of total
      mass), secondary organic carbon/mobile sources, crustal sources, biomass burning,
      nitrate, various industrial processes, and sea salt. The source apportionment
      tools and methodologies have passed the proof-of-concept stage and are now being
      used to understand the ambient composition of particulate matter for sites across
      the United States and the spatial relationship of sources to the receptor.
      Recommendations are made for further and standardized method development for
      source apportionment studies, and specific research areas of interest for the
      eastern United States are proposed.

PMID- 18069455
TI  - Fugitive emissions opacity determination using the digital opacity compliance
      system (DOCS).
AB  - Maintenance of Department of Defense (DoD) weapon systems, conducting battlefield
      training exercises as well as meeting military construction and/or demolition
      schedules, invariably generate fugitive air emissions, many of which are visible.
      Although there is no codified federal method for quantifying fugitive emissions
      opacity, many state and local air regulatory agencies have instituted enforceable
      fugitive emission opacity standards at DoD facilities. The current study focused
      on comparing the performance of the digital opacity compliance system (DOCS) with
      U.S. Environment Protection Agency Method 9 (Method 9) certified human observers
      in quantifying the visible opacity associated with fugitive emissions produced
      using a commercial fog generator. By systematically repositioning both DOCS
      cameras and Method 9-certified observers during field testing, differences in
      method performance as a function of observational locations were documented. At
      both the 30- and 300-ft off-set distances, opacity levels reported by the DOCS
      technology and Method 9-certified smoke readers were found to be statistically
      different at the 99% confidence level. Alternatively, at the 90- and 150-ft off
      set distances, results suggested that there was an insignificant difference at
      the 99% confidence level between the two methods. Comparing the magnitude of the
      each method's standard deviation suggested that, at the 30-ft off-set distance,
      the DOCS technology was consistently more precise than Method 9-certified readers
      regardless of the observer's downwind distance. However, at the 90, 150, and 300
      ft off-set distances, method precision seemed to vary as a function of both off
      set and downwind distance. The primary factor affecting the consistency in
      opacity measurements appeared to be the impact of ground-level air turbulence on
      fog plume dispersion and transport. Field observations demonstrated that
      localized wind shear played a critical and decisive role in how and to what
      extent fugitive emissions opacity could be determined, regardless of the method
      selected.

PMID- 18069456
TI  - Revised algorithm for estimating light extinction from IMPROVE particle
      speciation data.
AB  - The Interagency Monitoring of Protected Visual Environments (IMPROVE) particle
      monitoring network consists of approximately 160 sites at which fine particulate
      matter (PM2.5) mass and major species concentrations and course particulate
      matter (PM10) mass concentrations are determined by analysis of 24-hr duration
      sampling conducted on a 1-day-in-3 schedule A simple algorithm to estimate light
      extinction from the measured species concentrations was incorporated in the 1999
      Regional Haze Rule as the basis for the haze metric used to track haze trends. A
      revised algorithm was developed that is more consistent with the recent
      atmospheric aerosol literature and reduces bias for high and low light extinction
      extremes. The revised algorithm differs from the original algorithm in having a
      term for estimating sea salt light scattering from Cl(-) ion data, using 1.8
      instead of 1.4 for the mean ratio of organic mass to measured organic carbon,
      using site-specific Rayleigh scattering based on site elevation and mean
      temperature, employing a split component extinction efficiency associated with
      large and small size mode sulfate, nitrate and organic mass species, and adding a
      term for nitrogen dioxide (NO2) absorption for sites with NO2 concentration
      information. Light scattering estimates using the original and the revised
      algorithms are compared with nephelometer measurements at 21 IMPROVE monitoring
      sites. The revised algorithm reduces the underprediction of high haze periods and
      the overprediction of low haze periods compared with the performance of the
      original algorithm. This is most apparent at the hazier monitoring sites in the
      eastern United States. For each site, the PM10 composition for days selected as
      the best 20% and the worst 20% haze condition days are nearly identical
      regardless of whether the basis of selection was light scattering from the
      original or revised algorithms, or from nephelometer-measured light scattering.

PMID- 18069457
TI  - Effects of sulfur dioxide and oxides of nitrogen emission reductions on fine
      particulate matter mass concentrations: regional comparisons.
AB  - Two thermodynamic equilibrium models were applied to estimate changes in mean
      airborne fine particle (PM2.5) mass concentrations that could result from changes
      in ambient concentrations of sulfate, nitric acid, or ammonia in the southeastern
      United States, the midwestern United States, and central California. Pronounced
      regional differences were found. Southeastern sites exhibited the lowest current
      mean concentrations of nitrate, and the smallest predicted responses of PM2.5
      nitrate and mass concentrations to reductions of nitric acid, which is the
      principal reaction product of the oxidation of nitrogen dioxide (NO2) and the
      primary gas-phase precursor of fine particulate nitrate. Weak responses of PM2.5
      nitrate and mass concentrations to changes in nitric acid levels occurred even if
      sulfate concentrations were half of current levels. The midwestern sites showed
      higher levels of fine particulate nitrate, characterized by cold-season maxima,
      and were projected to show decreases in overall PM levels following decreases of
      either sulfate or nitric acid. For some midwestern sites, predicted PM2.5 nitrate
      concentrations increased as modeled sulfate levels declined, but sulfate
      reductions always reduced the predicted fine PM mass concentrations; PM2.5
      nitrate concentrations became more sensitive to reductions of nitric acid as
      modeled sulfate concentrations were decreased. The California sites currently
      have the highest mean concentrations of fine PM nitrate and the lowest mean
      concentrations of fine PM sulfate. Both the estimated PM2.5 nitrate and fine mass
      concentrations decreased in response to modeled reductions of nitric acid at all
      California sites. The results indicate important regional differences in expected
      PM2.5 mass concentration responses to changes in sulfate and nitrate precursors.
      Analyses of ambient data, such as described here, can be a key part of weight of
      evidence (WOE) demonstrations for PM2.5 attainment plans. Acquisition of the data
      may require special sampling efforts, especially for PM2.5 precursor
      concentration data.

PMID- 18069458
TI  - Estimating fine particulate matter component concentrations and size
      distributions using satellite-retrieved fractional aerosol optical depth: part 1-
      method development.
AB  - We develop a method that uses both the total column aerosol optical depth (AOD)
      and the fractional AOD values for different aerosol types, derived from
      Multiangle Imaging SpectroRadiometer (MISR) aerosol data, to estimate ground
      level concentrations of fine particulate matter (PM2.5) mass and its major
      constituents in eastern and western United States. Compared with previous
      research on linking column AOD with ground-level PM2.5, this method treats
      various MISR aerosol components as individual predictor variables. Therefore, the
      contributions of different particle types to PM2.5 concentrations can be
      estimated. When AOD is greater than 0.15, MISR is able to distinguish dust from
      non-dust particles with an uncertainty level of approximately 4%, and light
      absorbing from non-light-absorbing particles with an uncertainty level of
      approximately 20%. Further analysis shows that MISR Version 17 aerosol
      microphysical properties have good sensitivity and internal consistency among
      different mixture classes. The retrieval uncertainty of individual fractional
      AODs ranges between 5 and 11% in the eastern United States, and between 11 and
      31% in the west for non-dust aerosol components. These results provide confidence
      that the fractional AOD models with their inherent flexibility can make more
      accurate predictions of the concentrations of PM2.5 and its constituents.

PMID- 18069459
TI  - Estimating fine particulate matter component concentrations and size
      distributions using satellite-retrieved fractional aerosol optical depth: part 2-
      a case study.
AB  - We use the fractional aerosol optical depth (AOD) values derived from Multiangle
      Imaging Spectroradiometer (MISR) aerosol component measurements, along with
      aerosol transport model constraints, to estimate ground-level concentrations of
      fine particulate matter (PM2.5) mass and its major constituents in the
      continental United States. Regression models using fractional AODs predict PM2.5
      mass and sulfate (SO4) concentrations in both the eastern and western United
      States, and nitrate (NO3) concentrations in the western United States reasonably
      well, compared with the available ground-level U.S. Environment Protection Agency
      (EPA) measurements. These models show substantially improved predictive power
      when compared with similar models using total-column AOD as a single predictor,
      especially in the western United States. The relative contributions of the MISR
      aerosol components in these regression models are used to estimate size
      distributions of EPA PM2.5 species. This method captures the overall shapes of
      the size distributions of PM2.5 mass and SO4 particles in the east and west, and
      NO3 particles in the west. However, the estimated PM2.5 and SO4 mode diameters
      are smaller than those previously reported by monitoring studies conducted at
      ground level. This is likely due to the satellite sampling bias caused by the
      inability to retrieve aerosols through cloud cover, and the impact of particle
      hygroscopicity on measured particle size distributions at ground level.

PMID- 18069460
TI  - Laboratory evaluation of an aldehyde scrubber system specifically for the
      detection of acrolein.
AB  - We demonstrate the use of an aldehyde scrubber system to resolve isobaric
      aldehyde/alkene interferences in a proton transfer reaction mass spectrometer
      (PTR-MS) by selectively removing the aldehydes from the gas mixture without loss
      of quantitative information for the alkene components. The aldehyde scrubber
      system uses a bisulfite solution, which scrubs carbonyl compounds from the gas
      stream by forming water-soluble carbonyl bisulfite addition products, and has
      been evaluated using a synthetic mixture of acrolein and isoprene. Trapping
      efficiencies of acrolein exceeded 97%, whereas the transmission efficiency of
      isoprene was better than 92%. Quantification of the PTR-MS response to acrolein
      was validated through an intercomparison study that included two derivatization
      methods, dinitrophenylhydrazine (DNPH) and O-(4-cyano-2
      ethoxybenzyl)hydroxylamine (CNET), and a spectroscopic method using a quantum
      cascade laser infrared absorption spectroscopy (QCL) instrument. Finally, using
      cigarette smoke as a complex matrix, the acrolein content was assessed using the
      scrubber and compared with direct QCL-based detection.

PMID- 18069461
TI  - Characteristics of real-world vehicular emissions in Chinese cities.
AB  - On-board emission measurements were performed on 49 light-duty gasoline vehicles
      in seven cities of China. Vehicle-specific power mode distribution and emission
      characteristics were analyzed based on the data collected. The results of our
      study show that there were significant differences in different types of roads.
      The emission factors and fuel consumption rates on arterial roads and residential
      roads were approximately 1.4-2 times those on freeways. The carbon monoxide,
      hydrocarbon, and nitrogen oxides emission factors of Euro II vehicles were on
      average 86.2, 88.2, and 64.5% lower than those of carburetor vehicles,
      respectively. The new vehicle emission standards implemented in China had played
      an important role in reducing individual vehicle emissions. More comprehensive
      measures need to be considered to reduce the total amount of emissions from
      vehicles.

PMID- 18069462
TI  - Life cycle assessment of fuel selection for power generation in Taiwan.
AB  - Life cycle assessment (LCA) was applied to performance data from 1997-2002 to
      evaluate the environmental impacts of the energy input, airborne emission,
      waterborne emission, and solid waste inventories for Taiwan's electric power
      plants. Eco-indicator 95 was used to compare the differences among the generation
      processes and fuel purification. To better understand the environmental trends
      related to Taiwan's electric power industry, three fuel scenarios were selected
      for LCA system analysis. Results indicate that there are differences in
      characteristic environmental impact among the 13 power plants. Scenario
      simulation provided a basis for minimizing environmental impacts from fuel
      selection targets. Fuel selection priority should be a gas-fired combined cycle
      substituted for a coal-fired steam turbine to be more environmentally friendly,
      particularly in the areas of the greenhouse effect, acidification, winter smog,
      and solid waste. Furthermore, based purely on economic and environmental
      criteria, it is recommended that the gas-fired combined cycle be substituted for
      the oil-fired steam turbine.

PMID- 18069463
TI  - A statistical assessment of saturation and mobile sampling strategies to estimate
      long-term average concentrations across urban areas.
AB  - The objectives of this study were: (1) to quantify the errors associated with
      saturation air quality monitoring in estimating the long-term (i.e., annual and 5
      yr) mean at a given site from four 2-week measurements, once per season; and (2)
      to develop a sampling strategy to guide the deployment of mobile air quality
      facilities for characterizing intraurban gradients of air pollutants, that is, to
      determine how often a given location should be visited to obtain relatively
      accurate estimates of the mean air pollutant concentrations. Computer simulations
      were conducted by randomly sampling ambient monitoring data collected in six
      Canadian cities at a variety of settings (e.g., population-based sites, near
      roadway sites). The 5-yr (1998-2002) dataset consisted of hourly measurements of
      nitric oxide (NO), nitrogen dioxide (NO2), oxides of nitrogen (NOx), sulfur
      dioxide (SO2), coarse particulate matter (PM10), fine particulate matter (PM2.5),
      and CO. The strategy of randomly selecting one 2-week measurement per season to
      determine the annual or long-term average concentration yields estimates within
      30% of the true value 95% of the time for NO2, PM10 and NOx. Larger errors, up to
      50%, are expected for NO, SO2, PM2.5, and CO. Combining concentrations from 85
      random 1-hr visits per season provides annual and 5-yr average estimates within
      30% of the true value with good confidence. Overall, the magnitude of error in
      the estimates was strongly correlated with the variability of the pollutant. A
      better estimation can be expected for pollutants known to be less temporally
      variable and/or over geographic areas where concentrations are less variable. By
      using multiple sites located in different settings, the relationships determined
      for estimation error versus number of measurement periods used to determine long
      term average are expected to realistically portray the true distribution. Thus,
      the results should be a good indication of the potential errors one could expect
      in a variety of different cities, particularly in more northern latitudes.

PMID- 18069464
TI  - Preliminary application of one-level posterior lumbar interbody fusion with
      prospace and facet fusion using local autograft.
AB  - OBJECTIVE: To evaluate the safety and efficacy of one-level posterior lumbar
      interbody fusion (PLIF) combined with Prospace and facet fusion using local
      autograft. METHODS: Clinical and radiographic data of 76 patients treated by this
      technique was reviewed from May 2002 to December 2004. Of them, there were 52
      males and 24 females, with an average age of 53.2 years (23-81 years), including
      60 cases of degenerative disc disease, 9 cases of failed back surgery syndrome
      and 3 cases of spondylolysis.The disese courses were 1.2-8.7 years (mean 3.6
      years). The levels of PLIF were: L2,3 in 2 cases, L3,4 in 7, L4,5 in 54, L5/S1 in
      10, L4/ S1 in 1 and L5,6 in 2. After decompression, Prospace was inserted into
      interbody space bilaterally, and located in disc space 4 mm beyond the rear edge
      of the vertebral body. Local laminectomy autograft was packed both laterally into
      and between 2 implants. Then the remanent local autograft was placed over facet
      bed. Pedicle screws were used after insertion of Prospace. Clinical results were
      evaluated by the JOA score. Disc height ratio and lumbar lordosis angles were
      measured on lateral radiographs. Fusion status was determined by evidence of
      bridge trabeculae across facet joint and interbody space on CT scan without
      mobility in lateral dynamic X-rays, and no radiolucent gap between Prospace and
      endplate. Paired t-test was used for statistical analysis. RESULTS: Mean blood
      loss and operative time was 384 ml and 178 minutes, respectively. The average JOA
      score at final follow-up (26.1 +/- 2.7) was significantly improved when compared
      with that of pre-operation (14.5 +/- 4.0, P < 0.05), with a mean recovery rate of
      JOA score 81.1% (37.5%-100.0%). The fusion rate was 97.4% (74/76). Mean disc
      height ratio and the involved segmental lordosis angle were increased from
      preoperative 0.27 +/- 0.07 and 5.8 +/- 2.2 degrees to 0.33 +/- 0.06 and 11.3 +/-
      2.0 degrees respectively at the final follow-up, and the differences were
      significant (P < 0.05). There were no device-related complications. CONCLUSION:
      This surgical technique combined with Prospace interbody device is a safe and
      effective surgical option for patients with one-level lumbar disorders when PLIF
      is warranted.

PMID- 18069465
TI  - [Microsurgery and intervertebral fusion with anterior plating for cervical
      spondylitic radiculopathy].
AB  - OBJECTIVE: To introduce and evaluate the efficacy of microsurgical decompression
      and titanium cage implants fusion with anterior plating in cervical spondylitic
      radiculopathy. METHODS: From September 2000 to September 2002, 54 consecutive
      patients were treated with anterior microsurgical decompression followed by
      intervertebral fusion using a titanium cage packed with autogenous cancellous
      bone graft and an anterior cervical plating. There were 31 males and 23 females,
      with an average age of 45.2 years (38-65 years). The disease course was 5-19
      months. The locations were C3,4 in 3 cases, C4,5 in 25, C5,6 in 21 and C6.7 in 5
      cases. The bony endplates were preserved to prevent cage subsidence. Thirty-nine
      cases suffered from monosegmental fusion and 15 cases did bisegmental fusion. The
      Cobb angle was 0.80+/-0.31 degrees before operation. RESULTS: All wounds healed
      by first intention and no complications of vertebral artery injury, vertebral
      nerve injury and leakage of cerebrospinal fluid occurred. Dysphagia occurred
      within 2 weeks in 2 cases, hoarseness occurred and recovered without treatment in
      1 case, and pain in upper limbs aggravated and was relieved after 1 month of
      conservative treatment in 1 case. Fifty-four patients were followed 12-36 months
      (16.4 months on average). The X-ray films showed no breakage of screws and robs
      and olisthy of implants. Fusion was achieved in 53 patients and the fusion rate
      was 98.2%. The Cobb angles were 5.50+/-0.22 degrees after operation and 5.20+/
      0.17 degrees at final follow-up, showing significant differences when compared
      with before operation (P<0.01). According to Odom's criteria, the results were
      excellent in 24 cases, good in 22 cases and fair in 8 cases, the excellent and
      good rate was 85.2%. CONCLUSION: Anterior cervical microsurgical decompression is
      a safely and effectively treatment option in patients with cervical spondylitic
      radiculopathy caused by protrusion of intervertebral disc (1-2 discs) and by
      degenerative osteophyte. Titanium cage interbody fusion with concomitant use of
      anterior plating provides immediate biomechanical stability, successfully
      restores and maintains posterior interbody height and cervical lordosis to ensure
      satisfactory long-time outcomes.

PMID- 18069466
TI  - [Reconstruction of anterior cruciate ligament with different grafts under
      arthroscope in 68 cases].
AB  - OBJECTIVE: To study the clinical effect of anterior cruciate ligament (ACL)
      reconstruction with different grafts under arthroscope. METHODS: A retrospective
      analysis was done on 68 cases of ACL injury. ACL reconstruction with bone
      patellar tendon-bone autograft and interface screw fixation were performed in 26
      cases (group A) and quadruple semitendinosus tendon autograft and endobutton
      plate fixationin in 38 cases (group B). ACL reconstruction with bone-patellar
      tendon-bone allograft cryopreserved and interface screw fixation were performed
      in 4 cases (group C). There were 16 males and 10 females with an average age of
      26.4 years (16-45 years) in group A, 24 males and 14 females with an average age
      of 24.6 years (13-48 years) in group B, and 3 males and 1 female (55-65 years) in
      group C. The left knee involved in 14 cases, 27 cases and 3 cases, and the right
      knee involved in 12 cases, 11 cases and 1 case in groups A, B and C,
      respectively. The disease courses were 1 week to 15 months (group A), 1 week to
      16 months (group B) and 2 weeks to 28 months (group C). The intermediate
      myodynamic recovery, IKDC score and Lysholm score were compared among 3 groups.
      RESULTS: All patients were followed 12-36 months (17.5 months in group A, 18.5
      months in group B and 16.5 months in group C). No intra-articular infection,
      phlebothrombosis of leg, vascular injury and nerve injury occurred. Lysholm
      scores was increased from preoperative 65.3+/-4.8 to postoperative 95.1+/-4.3 in
      group A, from 68.4+/-5.6 to 93.0+/-5.9 in group B and from 60.3+/-6.7 to 92.2+/
      4.3 (excellent in 3 cases and good in 1 case) in group C; the excellent and good
      rates were 88.5% (excellent in 18 cases, good in 5 cases and fair in 3 cases) in
      group A, 86.8% (excellent in 28 cases, good in 5 cases and fair in 5 cases) in
      group B, IKDC scores were 93.7+/-3.8 (group A), 95.7+/-4.7 (group B) and 94.8+/
      3.6 (group C); the knee joint functions were normal in 19 cases (73.1%), in 30
      cases (78.9%) and in 3 cases, were fair in 5 cases (19.2%), in 5 cases (13.2%)
      and in 1 cases in groups A, B and C respectively. CONCLUSION: The transplantation
      of bone-patellar tendon-bone autograft , quadruple semitendinosus tendon
      autograft and bone-patellar tendon-bone allograft all can reconstruct and
      strengthen the stability of knee joint. Bone-patellar tendon-bone allograft is
      better selection for the ACL injury in elder and quadruple semitendinosus tendon
      autograft is suitable to adolescent patients with disrupted ACL.

PMID- 18069467
TI  - [Comparison of LCP and locked intramedullary nailing fixation in treatment of
      tibial diaphysis fractures].
AB  - OBJECTIVE: To evaluate the treatment results of LCP and locked intramedullary
      nailing for tibial diaphysis fractures. METHODS: From October 2003 to April 2006,
      55 patients with tibial diaphysis fractures (58 fractures) were treated. Of them
      there were 39 males and 16 females with an average of 39 years years ( 14 to 62
      years). The fractures were on the left side in 27 patients and on the right side
      in 31 patients (3 patients had bilateral involvement). Thirty-four fractures were
      treated by intramedullary nailing (intramedullary nailing group) and 24 fractures
      by LCP fixation (LCP group). The average disease course was 3 days
      (intramedullary nailing group) and 3.1 days (LCP group). The operation time, the
      range of motion of knee and ankle joints, fracture healing time, and
      complications were evaluated. RESULTS: The patients were followed up 8-26 months
      (13 months on average). The operation time was 84.0+/-9.2 min (intramedullary
      nailing group) and 69.0+/-8.4 min (LCP group); the average cost in hospital was
      yen 19,297.78 in the intramedullary nailing group and yen 14,116.55 in the LCP
      group respectively, showing significant differences (P < 0.05). The flexion and
      extension of knee joint was 139.0 +/- 3.7 degrees and 4.0 +/- 0.7 degrees in
      intramedullary nailing group and 149.0+/-4.2 degrees and 0+/-0.4 degrees in LCP
      group, showing no significant difference (P>0.05). The doral flexion and plantar
      flexion of ankle joint were 13.0+/-1.7 degrees and 41.0+/-2.6 degrees in
      intramedullary nailing group, and 10.0+/-1.4 degrees and 44.0+/-2.3 degrees in
      LCP group, showing no significant differences (P>0.05). The mean healing time was
      3.3 months in intramedullary nailing group, and 3. 1 months in LCP group. Length
      discrepancy occurred in 1 case (2.5 cm), delayed union in 1 case and nailing end
      trouble in 3 cases in intramedullary nailing group; moreover rotation deformity
      occurred 1 case and anterior knee pain occurred in 6 cases (17.1%). One
      angulation and open fracture developed osteomyelitis in 1 case 1 week
      postoperatively and angulation deformity occurred in 1 case of distal-third
      tibial fractures in LCP group. CONCLUSION: LCP and locked intramedullary nailing
      can achieve satisfactory results in treating tibial diaphysis fracture LCP has
      advantages in less complication, operation time and cost in hospital.

PMID- 18069469
TI  - [Biomechanical evaluation of glenohumeral ligament in holding anterior stability
      of shoulder joint].
AB  - OBJECTIVE: To investigate the effect of glenohumeral ligament (GHL) in static
      stabilizing structure of shoulder joint. METHODS: Fifteen upper limbs specimen
      from fresh adult corpse were made shoulder joint-bone ligament specimen and
      divided in 5 groups (n=3). The load-shift curve of the following specimen was
      measured respectively at the shoulder joint in abductive angles of 0 degrees, 45
      degrees and 90 degrees, influenced by 50 N posterior-anterior load to evaluate
      anterior stability of shoulder joint. According to different selective-cutting
      test, 5 groups were divided subgroups: group A (A1-A4), respectively normal
      group, superior GHL (SGHL) injury group; SGHL/middle GHL (MGHL) injury group and
      SGHL/MGHL/inferior GHL (IGHL) injury group; group B (B1-B3), respectively normal
      group, MGHL injury group, MGHL/IGHL injury group; group C (C1-C2), respectively
      normal group, IGHL-anterior band (IGHL-AB) injury group; group D D1-D2),
      respectively normal group, IGHL-posterior band (IGHL-PB) injury group; and group
      E (E1-E2), respectively normal group, IGHL injury group. RESULTS: For complete
      shoulder joint (A1 group), there was very small average shift (15.00+/-4.99 mm),
      for A4 group, there was the worst stability of shoulder joint, the average shift
      was 22.34+/-5.70 mm. For B2 group, the stability of shoulder joint had no obvious
      decrease. For B3 group, the stability of shoulder joint was worst at abduction
      angle of 45 degrees and 90 degrees. For C2 group, the stability of shoulder joint
      at abduction angle of 45 degrees (23.19+/-4.58 mm) and 90 degrees (15.32+/-1.30
      mm) was worse than that of A1 group (P<0.05); half-dislocation or dislocation
      could be seen. For D2 group (17.30+/-4.93 mm), there was less effect on anterior
      stability of shoulder joint than that of A1 group (P<0.05). For E2 group (20.26+/
      4.75 mm), the effect on anterior stability was similar to C2 group. CONCLUSION:
      GHL is a key static stabilizing structure of shoulder joint. SGHL has no obvious
      effect on anterior stability of shoulder joint. MGHL and IGHL together holds
      anterior stability of shoulder joint, and IGHL plays the most important role.

PMID- 18069468
TI  - [Dynamia correction of hallux valgus deformity with musculus extensor hallucis
      longus shifting].
AB  - OBJECTIVE: To discuss the mechanisms and clinical effect of musculus extensor
      hallucis longus shifting in correcting hallux valgus (HV) deformity. METHODS:
      From April 2004 to December 2006, 25 cases of HV (38 feet) were treated by
      musculus extensor hallucis longus shifting. There were 2 men and 23 women, aging
      from 22-60 years (mean 46.3 years). HV angle was 21-45 degrees (mean 31.30
      degrees), intermetatarsal (IM) angle was 7-21 degrees (mean 12.52 degrees). The
      HV were corrected by cutting osteophyma of the first metatarsal bone, cutting
      transverse head of adductor pollicis, transferring musculus extensor hallucis
      longus and reconstructing its insertion. RESULTS: The patients were followed up 6
      14 months after operation. HV angle and IM angle were 7.30 degrees +/- 2.62
      degrees and 6.50 degrees +/- 2.46 degrees respectively, showing significant
      differences when compared with before operation (P < 0.05). According to the
      American Orthopaedic Foot & Ankle Society (AOFAS) score system, the foot function
      was excellent in 25 feet, good in 7 feet and poor in 6 feet, and the excellent
      and good rate was 84.2%. Hallux varus occurred in 2 feet after 2 months of
      operation, metatarsophalangeal joint limitation of motion in 2 feet after 3
      months of operation, no HV recurred. CONCLUSION: The HV deforemity can be
      corrected by shifting the musculus extensor hallucis longus and reconstructing
      its insertion. It makes stress of metatarsophalangeal joint balance and prevent
      recurrance of HV deformity.

PMID- 18069470
TI  - [Src activation required for pERK1/2 activation in focal adhesions in osteoblasts
      induced by platelet-derived growth factor].
AB  - OBJECTIVE: To study the function of platelet-derived growth factor (PDGF) in
      inducing phosphorylation extracellular signal-regulated kinase 1/2 (pERK1/2)
      localization in osteoblasts. METHODS: Primary osteoblasts were isolated and
      cultured from cranial bone of 10 mice at the age of 3 days, weighting 6-9 g
      without limitation in male and female. The sixth passage osteoblasts were
      incubated in 1% serum for 12 hours and divided into 2 groups: treated with DMSO
      (control group) or with PP2 (experimental group) for 30 minutes. Each group was
      further divided into 2 subgroups according to with or without PDGF (20 ng/ml)
      stimulation for 10 minutes. pERK1/2 localization was analysized by
      immunofluorescence staining in osteoblasts pretreated with or without Src
      inhibitor PP2. The sixth passage osteoblasts were divided into 2 groups treated
      with DMSO (control group) or with PP2 (experimental group) for 30 minutes. Each
      group was further divided into two subgroups according to with or without PDGF
      (20 ng/ml) stimulation for 10 mintues. The ability of osteoblast migration was
      determined by wound healing assay. The sixth passage osteoblasts were divided
      into 2 groups treated with DMSO (control group) or 10 micromol/L PP2
      (experimental group) for 30 mintues. Each group was further divided into 2
      subgroups according to with or without PDGF (20 ng/ml) stimulation. The pERK1/2
      was determined by Western blot in osteoblastic cytoskeleton induced by PDGF.
      RESULTS: Immunofluorescence staining showed pERK1/2 localization in osteoblastic
      nuclears and focal adhesions after PDGF stimulation. PP2 significantly inhibited
      ERK1/2 localization in focal adhesions, but not in nuclears. The wound healing
      assay results showed that PP2 significantly inhibited osteoblast migration
      induced by PDGF. The result of Western blot demonstrated that pERK1/2 in
      osteoblastic cytoskeleton was significantly inhibited. CONCLUSION: Src activation
      is required for pERK1/2 translocalization to focal adhesions and osteoblasts
      migration.

PMID- 18069471
TI  - [An experimental study on ectopic osteogenesis of autologous micromorselized bone
      compounded with slow-released rhBMP-2/PLGA microsphere].
AB  - OBJECTIVE: To observe the release pattern of the microcysts and the effect of
      ectopic osteogenesis of combined micromorselized bone by optimized preparation of
      microcysts. METHODS: Optimized poly-DL-lactide-coglycolide (PLGA) microcysts
      manufacturing method was performed with the orthogonal design, and the
      accumulated release amount of microcysts was calculated at 2 h, 4 h, 8 h, 12 h,
      24 h, 36 h, 48 h, 60 h, 72 h, 84 h, 96 h, 120 h, 144 h, 168 h, 192 h, 216 h, 240
      h and 264 h. Twenty-four Wistar rats were divided into 4 groups (n=6) and 1 cm
      length incision was cut in their bilateral thighs skin, forming 48 gluteus
      maximus muscle sack models. In group A, collagen was implanted to bilateral
      muscle sacks respectively. In group B, collagen and autologous morselized bone
      were implanted to bilateral muscle sacks. In group C, collagen and rhBMP-2/PLGA
      delayed release microcysts were implanted to bilateral muscle sacks respectively.
      In group D, collagen and morselized bone/rhBMP-2/PLGA delayed release microcysts
      were implanted to bilateral muscle sacks. Gross and histologic observations were
      made at 3, 4 and 5 weeks postoperatively. RESULTS: Every optimized variance had
      an effect on particle diameter of microcyst and its encapsulating rate. The
      microcyst's surface was smooth and had a fine spheroplast, which released slowly
      within 11 days in vitro. In the third week postoperatively, the graft in group A
      could not be touched, while the graft in all other 3 groups was still found.
      After 3 weeks, collagen was absorbed completely in group A, the residual collagen
      could be seen in groups B, C and D. After 4 weeks, collagen could be seen in
      group A; micromorselized bone continued to be absorbed and became smaller in
      group B; microsphere became smaller, osteoblasts increased in group C;
      micromorselized bone and microsphere continued to be absorbed, oteoblasts and
      chondroblasts increased. After 5 weeks, implants became small, microsphere was
      absorbed, osteoblasts and chondroblasts became more in groups B, C and D.
      Microcysts presented with white granulo-shape and were packaged in tissue pieces.
      Histologic observation showed that the PLGA microcysts in 3 weeks and 4 weeks
      could be absorbed gradually as the time in vivo, if combining with morselized
      bone they could produce abundant induced osteoblasts and chondroblasts.
      CONCLUSION: Optimizing the preparation technology of microcysts has delayed their
      release during a long period in vitro. Autologous micromorselized bone can be
      ectopicly induced to produce large amount of osteoblasts in gluteus maximus
      muscle sack, where PLGA microcysts can combine organically and bring about the
      bone formation with less amount of growth factors.

PMID- 18069472
TI  - [Study on repair of critical calvarial defects with nano
      hydroxyapatite/collagen/polylactic acid material compounded recombinant human
      bone morphogenetic protein 2 in rabbits].
AB  - OBJECTIVE: To investigate the effect of tissue engineering bone compounded in
      vitro by nano-hydroxy-apatite/collagen/polylactic acid (nHAC/PLA) and recombinant
      human bone morphogenetic protein 2 (rhBMP-2) in repairing rabbit critical
      calvarial defects. METHODS: Forty-eight New Zealand rabbits, weighting 2.0-2.5
      kg, were made the models of critical cranial defects (15 mm in diameter) and
      divided into 4 groups randomly. Defects were repaired with auto-flank bone in the
      positive control group; with no implant in the blank control group; with nHAC/
      PLA in the negative control; and with active nHAC/PLA(AnHAC/PLA) in the
      experimental group(the average quality of each AnHAC/PLA absorbed rhBMP-2 was
      1.431 mg). The reapir results were observed through X-ray,HE dyeing and Masson's
      trichrism dyeing after 8 and 16 weeks. RESULTS: The difference of bone formation
      was observed by X-ray block degree of skull defect area at 8 and 16 weeks. In the
      8 th week and 16 th week, the radiopacities on cranial defect were 67.21%+/-2.06%
      and 86.48%+/-1.73% in the positive control group; 5.84%+/-1.92% and 9.48%+/-2.72%
      in the blank control group; 19.13%+/-2.51% and 35.67%+/-3.28% in the negative
      control group; and 58.84%+/-2.55% and 85.61%+/-3.36% in the experimental group.
      There were significant differences between the negative control and the positive
      control group, and between the experimental group and the positive control group
      at 8 weeks (P<0.05). There were significant differences between the negative
      control and blank group, and between the experiment and the blank group at 8 and
      16 weeks (P<0.05). The histology observation showed that the width of bone
      trabecula at 16 weeks was more than that at 8 weeks and bone defect was full of
      bone tissue in positive control group. The bone defect was full of fibrous tissue
      at 8 and 16 weeks, and there was no new bone in the blank group. The bone defect
      was full of remnant material and fibrous tissue in the negative control group.
      The implanted area was replaced by the new bone at 8 weeks and the new bone was
      lamellar at 16 weeks in the experimental group; the residual material was less in
      defect area and there were more osteoblasts surrounding. CONCLUSION: The nHAC/PLA
      is a good scaffold material of rhBMP-2 and AnHAC/PLA has a good ability in
      repairing bone defect. So it is hopeful to be applied in the clinical repair of
      large bone defect.

PMID- 18069473
TI  - [Anatomical study on anterior transposition of ulnar nerve accompanied with
      arteries for cubital tunnel syndrome].
AB  - OBJECTIVE: To investigate the blood supply of the ulnar nerve in the elbow region
      and to design the procedure of anterior transposition of ulnar nerve accompanied
      with arteries for cubital tunnel syndrome. METHODS: The vascularity of the ulnar
      nerve was observed and measured in 20 adult cadaver upper limb specimens. And the
      clinical surgical procedure was imitated in 3 adult cadaver upper limb specimens.
      RESULTS: There were three major arteries to supply the ulnar nerve at the elbow
      region: the superior ulnar collateral artery, the inferior ulnar collateral
      artery and the posterior ulnar recurrent artery. The distances from arterial
      origin to the medial epicondyle were 14.2+/-0.9, 4.2+/-0.6 and 4.8+/-1.1 cm
      respectively. And the total length of the vessels travelling alone with the ulnar
      nerve were 15.0+/-1.3, 5.1+/-0.3 and 5.6+/-0.9 cm. The external diameter of the
      arteries at the beginning spot were 1.5+/-0.5, 1.2+/-0.3 and 1.4+/-0.5 mm
      respectively. The perpendicular distance of the three arteries were 1.2+/-0.5,
      2.7+/-0.9 and 1.3+/-0. 5 cm respectively. CONCLUSION: It is feasible to perform
      anterior transposition of the ulnar nerve accompanied with arteries for cubital
      tunnel syndrome. And the procedure preserves the blood supply of the ulnar nerve
      following transposition.

PMID- 18069474
TI  - [A method for quantifying vessel anastomosis in skin flap].
AB  - OBJECTIVE: To present a method for quantifying the anastomosis between two
      vessels based on angiograpy and provide a theoretical basis for vascular study in
      skin flap. METHODS: Ten bilateral skin flaps of 20 cm x 20 cm based on deep iliac
      circumflex vessels were elevated from the abdominal wall including musculus
      rectus abdominis and deep superior epigastric vessels in 5 minipigs which were
      100-115 cm in length and 25-35 kg in weight. One side was inserted an expander
      under the panniculus carnosus and was expanded regularly with 30-40 ml isotonic
      Na chloride injection (expanded group) and the other was unexpanded group which
      were without any treatment. A X-ray image of the flap vessles was obtained after
      a gelatin-lead oxide mixture was carotid arterially injected and 24 hours of
      cryopreservation of the body. Three parallel lines with equal interval
      perpendicular to long axis of the two vessels were designed at the communication
      area. Vessel anastomosis quantifying was determined by counting the number of
      marks derived from the intersections of the lines and the vessels and statistical
      analysis was carried out. RESULTS: The mark of intersection in expanded group
      (81.20+/-10.33) was more than that in unexpanded group (22.40+/-5.41), showing
      significant difference (P<0.01). CONCLUSION: The method for quantifying vessel
      anastomosis in skin flap is simple, reliable, and easy-to-perform. The principles
      of this procedure may also be applied to other experimental and clinical studies.

PMID- 18069475
TI  - [Correlation of the expression of melanocortin 1 receptor and melanin contents in
      human skin autografts].
AB  - OBJECTIVE: To detect the expression of melanocortin 1 receptor (MC-1R) and the
      melanin contents in human skin autografts and the normal skin, to elucide the
      role of MC-1R in hyperpigmented process of skin autografts. METHODS: Skin
      autografts and normal skin samples were obtained from skin graft on neck who need
      reoperation to release contractures after 1 year of operations.
      Immunohistochemical technique was performed to detect the expression and
      distribution of MC-1R in skin autografts (include full thickenss skin autografts,
      medium thickness skin autografts, and razor-thin skin autografts) and normal skin
      respectively. Masson-Fontana staining technique was performed to detect the
      melanin contents in all sorts specimens respectively. RESULTS: The expression of
      MC-1R was located on cell membrane and cytoplasm of melanocyte and keratinocyte
      in epidermal. The expression of MC-1R in most skin autografts was much stronger
      than that of control normal skins; the thinner skin autografts were, the more
      obvious expressions of MC-1R in skin autografts were. The expressions of MC-1R in
      all sorts of skin autografts were of significant differences compared with that
      in normal skins(P<0.01); the expression of MC-1R in normal skin of donor area was
      no significant differences compared with normal skin around recipient area
      (P>0.01). The contents of melanin in skin autografts were increased obviously and
      there were significant differences compared with that in normal skins (P<0.01);
      the contents of melanin among all sorts of skin autografts were of significant
      differences (P<0.01). The thinner skin autografts were, the more melanin contents
      in skin autografts. The expression of MC-1R was positively correlated with the
      contents of melanin in epidermis. CONCLUSION: The expression of MC-1R in skin
      autografts is significantly higher than that in normal skin and is correlated
      positively with the contents of melanin in skin autografts. Overexpression of MC
      1R may play an important role in hyperpigmented process of skin autografts.

PMID- 18069476
TI  - [Clinical application of latissimus dorsi musculocutaneous flap with a few muscle
      in repairing soft tissue defect of lower limbs].
AB  - OBJECTIVE: To explore the clinical effect of latissimus dorsi musculocutaneous
      flap with a few muscle in repairing the soft tissue defect of lower limbs.
      METHODS: From June 2000 to December 2006, 8 patients with soft tissue defects of
      lower limbs were repaired with the latissimus dorsi musculocutaneous flaps. There
      were 6 males and 2 females, aged from 25-69 years. The locations were heel in 3
      cases, dorsum pedis in 2 cases, anticnemion in 2 cases, and the right leg
      (squamous carcinoma) in 1 case. The area of soft defect ranged from 10 cm x 7 cm 
      18 cm x 12 cm. The flap in size ranged from 15 cm x 8 cm to 22 cm x 15 cm.
      RESULTS: Of all the flaps, 6 survived, 1 had vascular necrosis 2 hours after
      operation and survived by skin grafts, 1 had delayed healing because of
      infection. The wound and, donor site achieved primary healing. The follow-up for
      3 to 12 months revealed that all the flaps had a good appearance. The function of
      donor site was as normal. CONCLUSION: It is an ideal method to repair the soft
      tissue defect of lower limbs with latissimus dorsi musculocutaneous flap.

PMID- 18069477
TI  - [Repair of deep wounds of the foot and ankle].
AB  - OBJECTIVE: To summarize the clinical effects of the repairing methods for deep
      wounds of the foot and ankle. METHODS: From March 2002 to June 2006, 49 patients
      with skin and deep tissue defects of the foot and ankle underwent the repairing
      treatment. Of them, 36 were males and 13 were females, aged 16 to 67 years( 39
      years on average). The causes of injuries included mangled injury in 24 cases,
      high fall injury in 9 cases, cut injury in 7 cases, malignant soft tissue tumor
      in 5 cases, decubital ulcer in 2 cases, and electric burn in 2 cases. Of the 49
      cases, 19 were in left side and 30 in right side. The defect size of skin ranged
      from 3 cm x 2 cm to 20 cm x 15 cm and deep tissue injuries were accompanied by
      defects of tendon and ligament in 24 cases, by damage of joint in 12 cases, and
      by bone defect in 9 cases, and 35 of them had infections, and 2 of them had
      diabetes of stage 2. The time between the injury and surgery ranged from 4 hours
      to 1 year. The wounds were repaired separately by local flap (3 cm x 3 cm to 6 cm
      x 4 cm) in 15 cases, local island flap(8 cm x 5 cm to 12 cm x 7 cm) in 25 cases,
      free flap (15 cm x 11 cm to 24 cm x 17 cm) in 4 cases, and cross leg flap(5 cm x
      4 cm to 8 cm x 6 cm) in 5 cases. In 24 cases of defects of tendon and ligament,
      15 underwent the reconstruction in one-stage operations, 9 in two-satge
      operation. In 9 cases accompanied by bone defect, two-stage bone grafting (12-64
      g) was given after wound healed. RESULTS: All of the 49 flaps survived. Forty-six
      healed by the first intention and 3 with distal edge necrosis healed after skin
      grafting. Two patients with sinus formation healed after 6-8 months of dressing
      change. All the cases were followed up 6 months to 3 years, and all the flaps
      were well developed, the functions of the foot and ankle were satisfactory.
      CONCLUSION: It can get an excellent result of appearance and function recovery
      repairing deep wounds of the foot and ankle with proper flaps in earlier time.

PMID- 18069478
TI  - [Surgical treatment of perineal Paget's disease].
AB  - OBJECTIVE: To investigate the surgical methods and effects of perineal Paget's
      disease. METHODS: From January 1998 to September 2004, 20 perineal Paget's
      disease cases were treated with several surgical methods. All the patients were
      male. Their ages ranged from 47 to 80 years. The courses of diseases ranged from
      1 year to 9 years (4.7 years on average). Among them, 14 cases involved scrotums
      purely, 5 cases involved scrotums and penises, 1 cases involved scrotum, penis
      and hypogastric zone. Fifteen cases were diagnosed as having Paget's disease
      through pathological exam. No metastasis was found before operation. RESULTS: The
      wounds healed by first intention in 19 cases, the free skin graft necrosed
      partially in 1 case and healed by second intention after dress-changing. All the
      patients were followed up 2 to 5 years, the contours of scrotums and penises were
      good. Two cases had tumor recurrence and received surgery again. Recurvation
      occurred in 2 cases during penis erecting, and was corrected by regional flap
      transplantation. CONCLUSION: The lesions like eczema in perineal reigon should be
      suspected as Paget's disease, and should be biopsied earlier. Complete removal by
      surgery is the only effective treatment. Perineal Padget's disease should be
      diagnosed and treated earlier. If the raw surfaces could not be repaired
      completely, flap transplantation and free skin graft should be used . The
      patients should be followed up closely.

PMID- 18069479
TI  - [Study on efficacy and safety of bioactive material--combest in treating burn].
AB  - OBJECTIVE: To explore the efficacy and safety of bioactive material (combest)
      which is combinated with bioglass and hyaluronan on burn wound healing. METHODS:
      From March to September 2006, 20 patients were treated; including 16 males and 4
      females, aging 18-58 years(40 years on average). The wounds were classified as
      deep degrees II in 7 cases, granulated wounds in 9 cases and graft site wounds in
      4 cases. Twenty wounds in one side were repaired with Combest as the test group
      and 20 wounds in the other side with blank cream as the control group. The wounds
      in size ranged from 2.0 cm x 1.5 cm to 40.0 cm x 20.0 cm. The wound healing rate
      was observed, and the blood test and the indices of hepatic and renal function
      were determined on the 1st, 3 rd, 6 th, 11 th, 16 th and 21 st days of treatment.
      RESULTS: Wound healed within 3 weeks in 11 cases of the test group (3 cases on
      the 11 st day, 4 on the 16 th day, and 4 on the 21 st day) , but no wound healing
      was observed within 3 weeks in the control group. The healing size accounted for
      2/3 of wounds in 18 cases of the test group and in 1 case of the control group.
      The excellent and good rates were 95%(18 cases and 1 case) in the test group and
      50% (1 case and 9 cases) in the control group, showing significant difference
      (P<0.01). For all patients, no obvious changes were found in the blood test and
      hepatic or renal function indices. CONCLUSION: Combest combinated with bioglass
      and hyaluronan is beneficial to the proliferation of the granulation and wound
      healing with good safety.

PMID- 18069480
TI  - [One-stage surgical treatment of congenital blepharophimosis syndrome].
AB  - OBJECTIVE: To explore the clinical effect of combining medial and lateral
      canthoplasty with blepharoptosis correction at one-stage for congenital
      blepharophimosis syndrome. METHODS: From January 2002 to May 2006, 26 patients
      (52 sides) with congenital blepharophimosis syndrome were treated. There were 16
      males and 10 females, aging from 3 to 35 years (mean 8.5 years). They were all
      bilateral blepharoptosis significantly. The palpebral muscle force was 0-3 mm;
      the transverse dimension and vertical dimension of the palpebral tissue were 13
      22 mm and 2-4 mm; the intercanthal distance was 33-44 mm; the levator function
      was 1-3 mm. RESULTS: Twenty-six patients underwent medial canthoplasty and
      blepharoptosis correction of them. 12 patients were also given lateral
      canthoplasty at one-stage. The postoperative transverse dimension and vertical
      dimension of the palpebral tissue were 6-8 mm and 24-32 mm, respectively. The
      intercanthal distance was 29-34 mm. The levator function was 4-6 mm. The
      supratarsal fold in the upper lid was natural. With a follow up of 3 months to 4
      years. all patients were satisfied with their results. CONCLUSION: One-stage
      surgical treatment of combining medial and lateral canthoplasty with
      blepharoptosis correction can achieve good result for blepharophimosis syndrome
      with a shortened treatment time.

PMID- 18069481
TI  - [Characteristics of osteoblastic differentiation in mesenchymal stem cells from
      porcine bone marrow in vitro].
AB  - OBJECTIVE: To observe the characteristics and related gene expression of
      osteoblastic differentiation in porcine bone marrow mesenchymal stem cells (MSCs)
      during. METHODS: Bone marrow from 6 landrace pigs, 3-month-old about 50 kg, was
      aspirated from the medullary cavity of the proximal tibia. The MSCs were
      isolated, and purified by Ficoll density gradient centrifugation combined with
      adherent culture method. The MSCs from passage 1 were cultivated in DMEM with 1 x
      10(-8) mmol/L dexamethasone (Dex), 10 mmol/L beta-glycerophosphate (beta-GP), 82
      microg/ml ascorbic acid (Asc) and 10% inactivated fetal bovine serum (FBS) up to
      21 days. The MSCs were cultivated in basic DMEM as a control. Cell morphology was
      observed by microscope. Cell proliferation was tested by using the fluorescent
      dye SYBR green I measurement. Osteoblastic differentiation was evaluated by
      alkaline phosphatase (ALP) histochemical staining, quantitative calcium deposit,
      and real-time PCR technology. RESULTS: Characterization of primary MSCs: At day
      1, most cells depicted round and floating hematopoietic cells. Colonies
      consisting of fibroblastlike cells were observed at day 3 after removal of non
      adherent cells, colonies grew to various sizes at day 7. Thirteen population
      doublings took place in primary culture. Osteoblastic differentiation: During
      osteogenic stimulation, cellular morphology of MSCs changed from a fibroblastic
      shape to a cubical form. Cell proliferation had no impact in osteogenic medium
      compared to basic medium (P>0.05). At day 14, ALP staining presented strong
      positive. Calcium deposit pronouncedly increased at day 21 (P<0.01). Furthermore,
      the mRNA levels of core binding factor alpha1 (Cbfalpha1), osterix, ALP, collagen
      I (Col I ), osteonectin (ON) and osteocalcin (OC) increased gradually. Cbfalpha1,
      ON and ALP genes increased at early stage of osteoblastic differentiation.
      Osterix and OC at day 21 were significantly increased when compared with that at
      day 7 (P<0.05). Col I was increased at day 14 (P<0.05). CONCLUSION: Porcine MSCs
      harvested from bone marrow by density gradient centrifugation are capable of
      osteoblastic differentiation in vitro. The potential of osteoblastic
      differentiation relies upon upregulation of genes specific to this lineage under
      the ostcogenic conditions.

PMID- 18069482
TI  - [Observation of replicative senescence of rat chondrocytes in vitro].
AB  - OBJECTIVE: To observe the replicative senescence of rat articular chondrocyte
      cultured in vitro so as to provide reference for the succeeding experiment of
      using medicine interfere and reverse the cataplasia of tissue engineering
      cartilage or probing cataplasia mechanism. METHODS: Different generations (P1,
      P2, P3 and P4) of the chondrocytes were detected with the methods of
      histochemistry for beta-galactosidase (beta-gal), electron-microscope for
      ultromicrostructure, immunocytochemistry for proliferating cell nuclear antigen
      (PCNA), alcian blue stain for content and structure of sulfat-glycosaminoglycan
      (GAG) of extracellular matrix (ECM), reverse transcription-polymerase chain
      reaction (RT-PCR) for content of collagen II, flow cytometry for cell life cycle
      and proliferative index(PI) to observe senescence of chondrocytes. RESULTS: In
      the 4th passage,the chondrocytes emerging quantitively positive express of beta
      gal, cyto-architecture cataplasia such as caryoplasm ratio increasing and
      karyopycnosis emerging under electron-microscope, cell life cycle being detented
      on G1 phase (83.8%), while in P1, P2, P3 the content of G1 phase was 79.1%,
      79.2%, 80.8% respectively. In the 4th passage, PI decreased (16.2%), while in P1,
      P2, P3, it was 20.9%, 20.8%, 19.2%. The positive percentage of PCNA, the content
      of GAG (long chain molecule) and the positive expression of collagen II
      diminished,all detections above were significantly different (P<0.01) when
      compared the 4th passage with the preceding passages. CONCLUSION: Chondrocytes
      show the onset of senescence in the 4th passage.

PMID- 18069483
TI  - [Repair of articular cartilage defect with poly-lactide-co-glycolide loaded with
      recombinant human bone morphogenetic protein in rabbits].
AB  - OBJECTIVE: To study the effect and feasibility of poly-lactide-co-glycolide
      (PLGA) loaded with recombinant human bone morphogenetic protein 2 (rhBMP-2) on
      repairing articular cartilage defect in rabbits. METHODS: PLGA was made into
      cylinders which were 4 mm in diameter and 3 mm in thickness. rhBMP-2 was fully
      homogenated before used. PLGA combined with 0.5 mg rhBMP-2 under the condition of
      vacuum (700 mmHg), and then lyophilized, packed, sterilized with ethylene oxide
      and reserved. Defects of 4 mm in diameter and reaching medullary cavity were made
      in femoral condyles of 72 two-month-old New Zealand white rabbits. The 36 right
      defects were repaired with PLGA-rhBMP-2 composites as the experimental group, the
      36 left defects with PLGA only as PLGA group, the other 36 left defects were left
      untreated as control group, and the other 36 right defects with PLGA-MSCs
      composites as cell group. At 4, 8, 12, 24, 36 and 48 weeks after operation,
      macroscopical and microscopical observations were made, and the histological
      grade was done. RESULTS: After 4 weeks of operation: In the experimental group
      and cell group, defects were filled with white translucent tissue which appeared
      smooth and soft; the matrix around chondrocytes was weakly metachromatic, the
      newly formed cartilage tissue was thicker than normal cartilage tissue; there was
      no formed tissue in the PLGA group and the blank control group. After 8 weeks of
      operation: In the experimental group and cell group, the new tissue was white,
      translucent, tenacious and smooth. The boundary with normal cartilage became
      vague. New cartilage cells distributed evenly. The cells of the surface layer
      paralleled, but the deeper layer lost directivity. The matrix dyed weakly. The
      new cartilage gradually became thinner, but it still thicker than the normal
      cartilage ones. The PLGA degraded besides some drops. In the blank control group
      and PLGA group, a little white membrane formed at the bottom of the defect. After
      12-24 weeks of operation: In the experimental group and cell group, defects were
      filled with new tissues which were white, translucent, tenacious and smooth. The
      boundary disappeared. The thickness of the new cartilage was similar to that of
      the normal ones. The cells of the surface layer paralleled to each other,but the
      cells of the deeper layer tended to arrange vertically. The matrix around
      chondrocytes was metachromatic, but the color was lighter than that of the normal
      cartilage. Bone under the cartilage and the tide mark recovered. The new
      cartilage linked with nomal cartilage finely. In the blank control group and PLGA
      group, there was a little fibrous tissue at the bottom of the defect withe
      obvious boundary. After 36 weeks and 48 weeks of operation: in the experimental
      group and the cell group, the new cartilage was slightly white, continuous and
      less smooth. The boundary disappeared. There was no proliferated synovial
      membrane. The thickenss of the new cartilage was thinner than that of the normal
      ones. The matrix around chondrocytes was weakly metachromatic. In the blank
      control group and PLGA group, the defect still existed, but became smaller. At
      the bottom of the defect, fibrous tissues formed. Some cartilage denudated and
      became less smooth. Some bone under cartilage exposed,and the synovial membrane
      became thick. The histologic grade of the repair tissue at 12 weeks and 24 weeks
      of operation in experimental group and cell group was significantly different
      from that at 4, 8 and 48 weeks of operation (P<0.01). There was also significant
      difference in the experimental group and cell group compared with the blank
      control group and PLGA group at each time after operation (P<0.01). But there was
      no significant difference between the experimental group and the cell group.
      CONCLUSION: In the course of degradation, PLGA-rhBMP-2 composites releas rhBMP-2,
      which then act an effect on MSCs around defect and induced them to differentiate
      for chondrocytes, and finally the defect is repaired. This simple and easy method
      may be used clinically in the future.

PMID- 18069484
TI  - [Experimental study on characterization of normal canine bladder transitional
      epithelial cells cultured in vitro].
AB  - OBJECTIVE: To explore an effective method to culture and purify canine bladder
      transitional epithelial cells. METHODS: Bladder tissue was obtained from healthy
      puppy under sterile conditions. Bladder mucosa was removed from the remaining
      tissue with fine scissor and minced into small pieces, and then were dissociated
      into single cell suspensions with 0. 125% trypsin. The bladder epithelial cells
      were cultured in defined keratinocyte serum free medium. The cells were passaged
      and purified by 0.05% trypsin and 0.02% EDTA. Morphological characterization were
      studied under inverted phase contrast microscope and transmission electron
      microscope. Expression of cell specific marker protein was assessed by
      immunohistochemistry. RESULTS: Canine bladder transitional epithelial cells could
      be efficiently cultivated and expanded in serum-free medium without fibroblast
      contamination. The cells could be passaged 4-6 times without a distinguished
      decrease in cell proliferation. The cells were characterized by well-developed
      microfilament and desmosome junction under transmission electron microscope.
      Immunohistochemical staining with broadly reacting anti-cytokeratin antibodies
      (AE1/AE3) confirmed the epithelial phenotype of the cells. Different generations
      of cells showed diploid cells. CONCLUSION: A large number of bladder transitional
      epithelial cells can be obtained from small bladder tissue with our digestion
      method. The cultured bladder epithelial cells can be proliferated to sufficient
      quantities for further reconstructive purposes.

PMID- 18069485
TI  - [Experimental study on tissue engineered testicular prosthesis with internal
      support].
AB  - OBJECTIVE: To investigate the feasibility and characteristic of tissue engineered
      testicular prosthesis with high-density polyethylene (HDPE, trade name: Medpor)
      and polyglycolic acid(PGA). METHODS: The chondrocytes were isolated from the
      swine articular. The PGA scaffold was incorporated with medpor which
      semidiameters were 6 mm and 4 mm respectively. Then, the chondrocytes (5 x
      10(7)/ml) were seeded onto Medpor-PGA scaffold and cultured for 2 weeks. The ten
      BALB/C mice were divided into two groups randomly (n = 5). In the experimental
      group, the cell-scaffold construct was implanted into subcutaneous pockets on the
      back of nude mice. In the control group, the Medpor-PGA scaffold was implanted.
      The mice of two groups were sacrificed to harvest the newly formed cartilage
      prosthesis after 8 weeks. Macroscopy, histology and immunohistochemistry
      observations were made. RESULTS: The gross observation showed that on changes
      were in shape and at size, the color and elasticity were similar to that of
      normal cartilage and that the cartilage integrated with Medpor in the
      experimental group; no cartilage formed and fiberlike tissue was found in the
      control group. HE staining showed that many mature cartilage lacuna formed
      without blood vessel and some PGA did not degradated completely. Toluidine blue
      staining showed extracellular matrix had metachromia. Safranin O-fast green
      staining showed that many proteoglycan deposited and collagen type II expression
      was strongly positive. In the control group, Medpor was encapsulated by fiber
      tissue with rich blood vessel. CONCLUSION: The newly formed complex of Medpor-PGA
      and cells was very similar to testicle in gross view and to normal cartilage in
      histology. This pilot technique of creating testicular prosthesis by
      incorporating tissue-engineered cartilage with Medpor demonstrated success.

PMID- 18069486
TI  - [Research progress of mesenchymal stem cells induced to differentiate
      intervertebral disc cells].
AB  - OBJECTIVE: To review the study progress of mesenchymal stem cells induced to
      differentiate intervertebral disc cells. METHODS: The recent related literature
      was reviewed. The theorical and experimental studies were summarized. RESULTS:
      MSCs had the potential of multi-directional differentiation. International
      experimental studies indicated the potential of MSCs induced to differentiate
      intervertebral disc cells. CONCLUSION: MSCs induced to differentiate
      intervertebral disc cells has the fine prospect.

PMID- 18069487
TI  - [Immunological investigation of repair of articular cartilage defects with
      allogeneic chondrocytes in porcins].
AB  - OBJECTIVE: To evaluate the immunological reaction and the outcome of allogeneic
      chondrocyte transplantation in repairing articular cartilage defects in porcins.
      METHODS: Full articular cartilage from the knee of two Shanghai white porcins
      about one-month-old was removed and cut mechanically, digested by 0.25% trypsin
      and 0.2% type II collagenase and cultured in 10% DMEM medium. Defects of 0.5 cm x
      0.5 cm involving the subchodral bone were created in both the left and right
      femur condyloid in 8 two-month-old Yunnai bama porcins. Allogeneic chondrocyte
      transplantation were implanted in defects at a density of (1.0-2.0) x 10(6), 0.2
      ml. The lymphocytes from the receivers' blood were collected before
      transplantation and after 3, 5, 7 and 12 weeks of transplantation, then mixed
      with allogeneic chondrocytes to determin the lymphocyte stimulation index(SI) in
      vitro. The histological observation in vivo was made after 5, 7 and 24 weeks of
      transplantation. RESULTS: Lymphocyte SI at 3, 5, 7 and 12 weeks (1.457 +/- 0.062,
      1.739 +/- 0.142, 1.548 +/- 0.047, 1.216 +/- 0.028) after transplantation was
      higher than that before transplantation (1.102 +/- 0.034, P<0.05). SI began to
      increase in the 3rd week and reached the peak value in the 5th week, then
      gradually declined at the 7th and 12th weeks, showing significant differences
      when compared with in the 5th week (P< 0.05). Inflammation and lymphocytes
      infiltration could be seen in subchondral bone and the intergration area between
      repair tissue and normal cartilage in the 5th week, and then decreased and
      limited in subchondral bone in the 7th week. Defects were filled with cartilage
      tissue, which had good intergration with subchondral bone at 24 weeks after
      transplantation. CONCLUSION: Immunological reactions can be found at early stage
      of allogeneic chondrocyte transplantation and then decreased with the time, the
      full-thickness articular cartilage defects could be repaired mainly with hyaline
      cartilage by the allogeneic chondrocyte transplantation. This may provide a new
      method to repair articular cartilage defects clinically.

PMID- 18069488
TI  - [Roles of leptin-mediated intracellular signaling pathways on wound healing].
AB  - OBJECTIVE: To study the leptin-mediated intracellular signal pathways and their
      effects on wound healing. METHODS: The literature was reviewed extensively,
      concerning the physical and chemical characters of leptin, the mechanism of its
      receptor action, the receptor-related intracellular signal pathways and their
      roles on wound healing. RESULTS: Leptin was a protein hormone expressed by ob
      gene with relative molecular mass 16 x 10(3), it could activate the main singal
      pathways such as Janus kinase/signal transducer and activator of transcription,
      mitogen-activated protein kinases and phosphoinositide-3-kinase pathways through
      binding with its specific receptor, to participate in the modulation of multiple
      functions including energy metabolism, weight balance and wound healing. Leptin
      receptors were widely distributed in various tissues, which suggest the multiple
      functions of leptin. Local leptin expression was increased after skin injured,
      and it could stimulate keratinocytes proliferation, epithelialization, fibroblast
      proliferation and collagen synthesis, resulting in accelarated wound repair.
      Leptin expression was significantly increased after mucosal injury or bacteria
      infections, leading to accelarated mucosal repair through modulation of mucosal
      glandular secretion, improvment of mucosal blood flow, and synergistic action
      with endothelin-1. CONCLUSION: Leptin can promote wound healing through
      activating its receptor-related intracellular signal pathways.

PMID- 18069489
TI  - [Research advances in animal models of intervertebral disc degeneration].
AB  - OBJECTIVE: To review the research advances in animal models of human disc
      degeneration. METHODS: The relative articles in recent years were extensively
      reviewed. Studies both at home and abroad were analyzed and classified. The
      advantages and disadvantages of each method were compared. RESULTS: Studies were
      classified as either experimentally induced models or spontaneous models. The
      induced models were subdivided as mechanical (alteration of forces on the normal
      disc), structural (injury or chemical alteration) and genetically induced models.
      Spontaneous models included those animals that naturally developed degenerative
      disc disease. CONCLUSION: Animal model of intervertebral disc degeneration is an
      important path for revealing the pathogenesis of human disc degeneration, and
      play an important role in testing novel interventions. With recent advances in
      the relevance of animal models and humans, it has a great prospect in study of
      human disc degeneration.

PMID- 18069490
TI  - [Standards used in the regulation of medical device in USA].
AB  - OBJECTIVE: To study the USA government's administrative system about medical
      device standards as well as the standard making. METHODS: The relevant documents,
      regulations, website that USA Food and Drug Administration announced were
      extensively reviewed, knowing the USA medical device standards synthetically.
      RESULTS: The USA standards system of medical device included regulatory
      requirements and voluntary consensus standards. This article simply introduced
      the laws, regulations, performance standards and consensus standards. CONCLUSION:
      The USA's administrative system about medical device standards as well as many
      standards can be referenced.

PMID- 18069491
TI  - Shake-up in education and careers will push nursing in new directions.

PMID- 18069492
TI  - Pandora maps the complexity of what clinical nurse specialists actually do.
      Interview by Adele Waters.

PMID- 18069493
TI  - Ray of hope.
AB  - The World Health Organization and International Council of Nurses have revealed a
      grim picture of global mental health services. But there are some glimmers of
      light.

PMID- 18069494
TI  - Dying art.
AB  - Working in a hospice gives nurses the opportunity to make patients' end of life
      peaceful, dignified and pain free.

PMID- 18069495
TI  - Reclaim the spirit.
AB  - A system of parish nursing allows patients to receive spiritual care integrated
      with their other needs. There are now 29 churches in the U.K. with at least one
      parish nurse.

PMID- 18069496
TI  - Powerful presence.

PMID- 18069497
TI  - Problem drinking.

PMID- 18069498
TI  - Complexities of policy-driven pre-registration nursing curricula.
AB  - This article discusses the challenges faced by two nurse educators when
      incorporating current health policy into a new pre-registration nursing
      curriculum, using public health and e-learning as examples. The article, which
      features the results of preliminary work from the authors' doctoral studies,
      includes summaries of students' discourses about e-learning and public health and
      how these subject areas are perceived by learners. Practical solutions to the
      challenges encountered are suggested.

PMID- 18069499
TI  - Monitoring and recording patients' neurological observations.
AB  - This article provides a detailed account of how to monitor and record
      neurological observations. It outlines the importance of neurological
      observations in acutely ill patients and focuses on carrying out observations
      using the Glasgow Coma Scale.

PMID- 18069500
TI  - Syphilis: clinical presentation, diagnosis and treatment.
AB  - Syphilis is a sexually transmitted infection that is increasing in the U.K. If
      left untreated it can have a number of potentially devastating health-related
      sequelae. However, effective treatment is available. Nurses working in various
      healthcare settings should be aware of the signs and symptoms of the infection to
      make a prompt diagnosis and appropriate referral for treatment.

PMID- 18069501
TI  - Erectile dysfunction.

PMID- 18069502
TI  - Difficult conversations.

PMID- 18069503
TI  - Esthetic dentistry: state of the art.
AB  - Over the past 30 years, the dental profession has changed from being mainly a
      pain-driven service orientation to including procedures that enhance the
      appearance of patients and improve their self-esteem and enjoyment of life. It
      has been estimated that approximately 50% of a typical American dentist's revenue
      is related to esthetic/ cosmetic procedures; it is predicted that this trend will
      continue. However, caution must be used to honestly provide all treatment
      possibilities, including expected treatment longevity, and to receive patient
      consent before providing irreversible esthetic procedures.

PMID- 18069504
TI  - The periodontal factor in esthetic smile design--altering gingival display.
AB  - The periodontal soft and hard tissues are an important determinant of restorative
      smile esthetics. Management of the periodontal tissues that "frame" each tooth is
      crucial to esthetic smile design. This article describes a four-step technique
      that makes it possible to sculpt the position of the labial gingival margin to
      provide additional crown height or length, a process the author describes as
      smile sculpting. This periodontal smile sculpting can aid in determining the pre
      restorative treatment profile for teeth and create a blueprint for the
      restorative dentist to enhance a patient's final esthetic treatment results.
      Crucial to understanding this process is an appreciation of the periodontal
      principles that govern smile design, especially the periodontal biologic width
      and the influence of the underlying hard tissue bony architecture in defining the
      periodontal envelope from which the teeth emerge.

PMID- 18069505
TI  - Preparation guidelines for less-invasive cosmetic restorations.
AB  - This article discusses the trend toward less-invasive restorative procedures. Two
      cases that required different approaches to similar restorations are documented.
      Understanding a systematic preparation philosophy allows clinicians to be
      consistent regarding both their approach and the expected results. The use of wax
      ups and preparation guides to achieve predictable esthetic restorations is shown,
      both visually and technically.

PMID- 18069506
TI  - Correction of the darkened anterior tooth: a new CLEAR approach to an old
      problem.
AB  - An anterior tooth that is darkened due to intrinsic staining can be a severe
      esthetic problem. Current treatment involving crowns and opacious porcelain
      veneers have some inherent disadvantages in terms of tooth conservation and the
      final result. The latest innovation in composite resin allows a minimal
      intervention approach for correcting this common problem. This article showcases
      a new layering approach for recreating natural esthetics.

PMID- 18069507
TI  - A simplified approach for layering composite resin restorations.
AB  - Although composite restorations can provide excellent results, it is possible
      that general dentists might find some of the currently proposed techniques to be
      complicated and demanding. This article reviews some of these concepts and
      presents a protocol that makes highly esthetic restorations simple yet
      predictable.

PMID- 18069508
TI  - Immediately loaded fixed hybrid prosthesis on a completely edentulous mandible: a
      case report using an indirect technique.
AB  - The immediate loading of implants has been a subject of controversy in the dental
      literature. At the same time, many patients prefer to have their teeth replaced
      as soon as possible without having to wear an immediate denture. Immediately
      loaded fixed hybrid prostheses have shown a high degree of clinical success and
      acceptance by patients. This article describes a case in which a provisional
      mandibular fixed hybrid prosthesis was placed within 24 hours of implant
      placement, followed by a final denture after complete osseointegration of all
      implants.

PMID- 18069509
TI  - All-ceramic inlay-retained fixed partial bridge using a CAD-CAM produced Y-TZP
      framework and fluoroapatite veneering ceramic: a clinical report.
AB  - All-ceramic materials have become an excellent option for both anterior and
      posterior fixed partial dentures (FPDs) due to advances in esthetic and
      mechanical properties. This clinical report describes the use of an all-ceramic
      inlay-retained three-unit FPD for replacement of a maxillary second premolar.
      Prosthetic restorative materials consisted of a CAD-CAM processed presintered
      yttrium stabilized zirconium oxide (Y-TZP) framework and a fluoroapatite
      veneering ceramic. The minimally invasive preparation technique and advantages of
      this highly esthetic and resistant treatment option are discussed.

PMID- 18069510
TI  - A cognitive systematic approach to analyzing preparation design for a difficult
      space management case.
AB  - There are at least two different techniques for preparing teeth prior to bonded
      porcelain restorations. The first involves using depth cutters guided by the
      existing tooth structure. A more recently developed approach integrates an
      additive wax-up that represents the final volume of the teeth, with indices used
      to guide the preparation design. This article illustrates in detail a clinical
      case that was prepared by combining the earlier simplified depth cutter approach
      with recontouring and preparation design principles determined clinically by the
      dentist. The same case was prepared in the laboratory on plastic models, using
      labial and incisal reduction preparation guides fabricated from a diagnostic wax
      up. This combination of techniques will simplify preparation design for difficult
      space management cases and facilitate predictable and repeatable results that
      meet current esthetic standards while staying conservative and preserving tooth
      structure.

PMID- 18069511
TI  - Randomized controlled trial of professional at-home tooth whitening in teenagers.
AB  - A randomized controlled clinical trial was conducted to compare two professional
      at-home tooth whitening systems in a teenage population. Informed consent and
      child assent were obtained from 60 teenagers aged 12-17 (mean age = 14.8). After
      baseline measurements, subjects were randomized to one of two groups, using
      either 14% hydrogen peroxide whitening strips or 10% carbamide peroxide in a
      custom bleaching tray. Strips were used for 30 minutes twice daily, while the
      tray was worn overnight. Treatment took place for 14 days sequentially, first on
      the maxillary arch and then on the mandibular arch; all use was unsupervised.
      Efficacy was measured objectively by L*a*b* color change from digital images
      obtained at baseline and end of treatment, using combined color measures for both
      arches. Both professional whitening systems had significant (p < 0.0001)
      reductions in yellowness (Deltab*) and increased lightness (DeltaL*) after two
      weeks of treatment on each arch. At the end of treatment, Deltab* or DeltaL* did
      not differ significantly between the groups (p > 0.28). Tooth sensitivity and
      mild oral irritation represented the most common adverse events, with only one
      subject discontinuing treatment as a result. Teenagers who used either bleaching
      method for two weeks experienced significant tooth whitening without serious
      adverse events.

PMID- 18069512
TI  - One-year follow-up of non-vital discolored teeth after bleaching with an
      association of techniques: a case report.
AB  - Patient demand for esthetic procedures and the trend for non-invasive dental
      treatment have led to the development of different materials and whitening
      techniques that are capable of re-establishing a patient's smile without
      affecting dental structure. Numerous potential factors may cause the
      discoloration of pulpless teeth. A simple and time-saving method for bleaching
      discolored root-filled teeth combines intracoronal and extracoronal bleaching
      with 35% hydrogen peroxide and a procedure known as the walking bleach technique,
      a conservative treatment that restores esthetics to darkened and stained non
      vital teeth. This article presents a case report that used this technique and
      examines the effects of this treatment after one year.

PMID- 18069513
TI  - Minimally invasive porcelain veneers: indications for a conservative esthetic
      dentistry treatment modality.
AB  - Patients have many restorative options for changing the appearance of their
      teeth. The most conservative restorative treatments for changing the appearance
      of teeth include tooth bleaching, direct composite resin veneers, and porcelain
      veneers. Patients seeking esthetic treatment should undergo a comprehensive
      clinical examination that includes an esthetic evaluation. When selecting a
      conservative treatment modality, the use of minimally invasive or no-preparation
      porcelain veneers should be considered. As with any treatment decision, the
      indications and contraindications must be considered before a definitive
      treatment plan is made. Long-term research has demonstrated a 94% survival rate
      for minimally invasive porcelain veneers. While conservation of tooth structure
      is important, so is selecting the right treatment modality for each patient based
      on clinical findings.

PMID- 18069514
TI  - Dental adhesives--the foundation of esthetic dentistry.
AB  - The clinical success of adhesive restorations depends on knowing the materials
      and how they are used in indicated areas. This article is designed to help
      clinicians understand the various protocols that are best suited for different
      clinical cases by discussing contemporary dental adhesive systems. The article
      also presents rationales for selecting adhesive systems for specific cavity
      classes, highlights the working principles underlying each clinical procedure,
      and explains technique problems in dental adhesive procedures. Clinical
      preventive measures to ensure longevity of direct adhesive restorations also are
      discussed.

PMID- 18069515
TI  - [Mechanisms of neuronal death in Huntington's disease. First part: general
      considerations and histopathological features].
AB  - Huntington's disease is caused by an abnormal CAG expansion within the gene
      encoding Huntingtin which induces a major cortico-striatal degeneration as well
      as motor and cognitive impairments. Since the discovery of the present mutation,
      a number of experimental data have been collected to uncover the
      physiopathological consequences of mutated Huntingtin expression. Here, we review
      the molecular and cellular mechanisms underlying and show how this better
      knowledge can be translate to clinical trials in patients.

PMID- 18069516
TI  - [Depenalized practice of euthanasia in Belgium: evolution from 2002 to 2005 and
      interpretation of the differences between the north and the south of the
      country].
AB  - The euthanasia's performed, in accordance with the law of may 28, 2002, between
      September 22, 2002 and December 31, 2003 and between January 1, 2004 and December
      31, 2005 are respectively analyzed in two successive reports of the federal
      commission for control and evaluation of euthanasia, based on the registration
      documents referred by the physicians to this commission. The present paper
      compares the data of those two reports and analyses the evolution of the
      application of the law. Apart from the number of euthanasia's per year, much
      greater in 2004-2005, the statistical data are very similar. The important
      difference in the number of registration documents written in French and in
      Dutch, already noted in the first report, is confirmed in 2004-2005. An
      interpretation is proposed.

PMID- 18069517
TI  - [Forensic approach of infanticide and neonatal death].
AB  - The foetal of neonatal death brings up many questions as well on the
      physiopathological level as on the medico-legal one. We consider here the various
      natural and violent origins which allow understanding this difficult forensic
      activity. The approach of forensic anthropology and recent medical techniques (X
      rays and echography) are also studied in order to be helpful to the medical
      examiner.

PMID- 18069518
TI  - [Uterine cervical carcinoma and pericardial effusion].
AB  - A 64-year-olf woman has been treated by chemotherapy for a uterine cervical
      carcinoma with known pathological lymph nodes in the abdomen and in the thorax.
      She is admitted in our Intensive Care Unit for fever and cardiac tamponade
      attributed to a large pericardial effusion. No diagnostic could be concluded from
      the analysis of the liquid or the pericardial biopsy. Complementary
      investigations are performed and the differential diagnosis of pericardial
      effusion is discussed in the context of a neoplastic disease.

PMID- 18069519
TI  - [Extracorporeal photochemotherapy: review of its mechanisms of action and
      clinical applications].
AB  - Extracorporeal photochemotherapy is an immunomodulatory treatment wich is carried
      out in three steps: first leukapheresis, then ex vivo PUVA treatment and finally
      autologous transfusion. Its current "evidence-based" indications are
      erythrodermic cutaneous lymphoma, graft versus host disease and cardiac graft
      rejection. However this treatment has already been used with success in many
      other diseases such as systemic sclerosis, multiple sclerosis, type 1 diabetes
      and various autoimmune dermatologic diseases. Randomised controlled studies are
      needed to confirm the efficacy of photopheresis in these diseases. We also review
      the different hypotheses explaining the mechanism of action of photopheresis.

PMID- 18069520
TI  - [Osteochemonecrosis of the jaws and bisphosphonates: a case report and literature
      review].
AB  - Jaws osteonecrosis were, in most cases, caused by external irradiation. It was
      otherwise a rare occurrence. However, bisphosphonates have recently been
      associated with osteonecrosis of the mandible or the maxilla. Bisphosphonates are
      widely used in the treatment of osteoporosis, multiple myeloma and osteolytic
      bone metastases. They inhibit bone resorption by osteoclasts and disrupt the bone
      turnover. The so-caused bone expositions are painful and prone to surinfection.
      Even after cessation of the bisphosphonates, the results of medical and surgical
      treatment are very inconsistent. A thorough dental check-up is recommended before
      initiating a course of bisphosphonates.

PMID- 18069521
TI  - [Klebsiella pneumoniae septicaemia and meningitis in a diabetic patient with an
      hepatic abscess].
AB  - Klebsiella pneumoniae infections show particular features depending on the
      geographical localization as well as comorbidity factors. We are presenting the
      case of a european patient with diabetes mellitus who presented a septicaemia, a
      meningitis as well as an hepatic abscess due to a K. pneumoniae and whose
      evolution was excellent under antibiotics. Usually described among Asian
      patients, the primary hepatic K. pneumoniae abscess, which is a clinical entity
      recently described, can give rise to potentially serious and multiple septic
      metastasis. We also discuss the diagnostic and therapeutic attitudes related to
      this infection.

PMID- 18069522
TI  - [Picture of the month: anatomy of an abscess].

PMID- 18069523
TI  - [Chronic renal disease. Primary care identification].
AB  - The prevalence of chronic kidney in the general population disease is increasing.
      The primary care physician can detect the first stage of chronic renal disease
      and can delay the progression to kidney failure. He can give special attention to
      patients with hypertension or with diabetes, or more than 60-year old, or with a
      familial history of chronic renal disease or with recurrent urinary infections.
      The detection of chronic renal disease can be done by measurement of the renal
      function (MDRD, Cockroft-Gault), by measurement of blood pressure and by
      detection of proteinuria. The treatment goals of chronic renal disease are
      defined after referral to a nephrologist.

PMID- 18069524
TI  - [The outset of heart transplantation in Belgium or the conjunction of resolute
      patients, trustful cardiologists and surgeon ready to go ahead].
AB  - The first heart transplantation (HTx) in Belgium was performed by us at
      university hospital Brugmann on August 23, 1973. At this time, organ procurement
      was still a sensitive procedure not regulated as well as it is nowadays. Among
      other difficulties, diagnosis of rejection after the operation was only based
      upon clinical signs and electrocardiographic voltage variations. Echocardiography
      did not exist yet and endocardiac biopsy was unknown. Moreover the variety of
      immunosuppressive drugs was scarce and their potency far from what we are used to
      in the present era. Three patients were transplanted with excellent immediate
      survival but nevertheless the first died after six months from an acute broncho
      pulmonary infection ; the second after one year of an ongoing chronic rejection
      and the third after two weeks of an acute rejection. Deeply frustrated by these
      unrewarding results alltogether for the patients and the doctors, it was decided
      to stop the programme until new progress would allow early and objective
      diagnosis of rejection and provide access to more potent immunosuppressive drugs.
      This became a reality in 1981 with the release of ciclosporine and the
      introduction in clinical practice of transvenous endocardiac biopsy to diagnose
      rejection and to monitor the outcome of its treatment further on. Those two
      opportunities were a major breaktrough for HTx which knew a spectacular revival
      worldwide. Ciclosporine arrived in Belgium in 1982 and we soon restarted HTx at
      Erasme Hospital. Comparing our results of HTx in the pre-ciclosporine period with
      the ones in the current era is striking. The cumulative 25 years experience of
      HTx at Erasme is briefly alluded to. We also remind that the first heart-lung
      transplantation (HLTx) in Belgium was performed by us in august 1983 at Erasme
      hospital credited to be the third center in Europe having successfully initiated
      this therapy for terminal heart-lung failure.

PMID- 18069525
TI  - [Non-payment of veterinary bills in The Netherlands].
AB  - Non-payment of bills is a phenomenon that has grave economic consequences for all
      entrepreneurs, veterinary practitioners included. Little in depth research has
      been performed into the non-payment of veterinary bills. The aim of this study
      was to quantify the non-payment of bills in Dutch veterinary practices and to
      investigate the procedures implemented in the case of non-payment and their
      effectiveness. Non-payment of bills is a potential source of a substantial loss
      of income in Dutch veterinary practices. Even though veterinarians actively tried
      to collect the money owed them, often bills were paid very late or were paid in
      part only.

PMID- 18069526
TI  - [A female, 3 year old cat with skin problems].

PMID- 18069527
TI  - [Pure blood].

PMID- 18069528
TI  - [Stem cells].

PMID- 18069529
TI  - [Are you as a veterinarian allowed to advertise for veterinary drugs?].

PMID- 18069530
TI  - [Summary of the Fourteenth International Congress: 'Lameness in Ruminants'].

PMID- 18069531
TI  - [KNMvD yearly Congress 'Wiser in Animal Welfare'. "We have to accept that animals
      sometimes get sick"].

PMID- 18069532
TI  - The doctor as expert witness--help or hindrance?

PMID- 18069533
TI  - Advance decision.
AB  - In the UK, patients have a statutory right to refuse treatment. Parliament has
      authorised 'advance decision' whereby a person can specify his or her wishes
      regarding further medical treatment. Although the advance decision may give a
      person peace of mind, it could create real problems for doctors and other
      healthcare professionals. This article will examine the conditions and procedures
      surrounding the drawing up of an advance decision as well as some of the problems
      that could arise such as layman's language.

PMID- 18069534
TI  - Challenges to implementation of the new Coroners' (Amendment) Rules 2005:
      experience from a tertiary paediatric pathology centre.
AB  - In the UK sudden unexpected childhood deaths are referred to Her Majesty's
      Coroner (HMC) for postmortem examination during which small tissue samples are
      obtained for diagnostic purposes. Recent changes to regulate tissue use include
      the Coroners' (Amendment) Rules 2005. We audited the impact of these at a
      specialist paediatric centre. A retrospective audit of HMC tissue forms for
      autopsies was performed between 1 June 2005 - 31 May 2006, with regard to the
      options provided to, and chosen by, parents. Of 213 coronial autopsies, 178 were
      non-forensic. Tissue forms were submitted pre-autopsy in 25 (14%). An additional
      47 were received after sending follow-up letters for a total of 72/178 (40%).
      Forms varied between coroners, but most failed to distinguish between blocks,
      slides, and other tissue samples and 6/40 (15%) forms did not specifically allow
      an option for research consent. Forty-three (60%) parents opted for retention,
      with 34 (79%) also consenting to research. Only six (8%) requested return of
      tissue. A simple, unified tissue disposal form and information sheet for all HMC
      districts, which includes appropriate options, would ensure that parents' wishes
      are met, to achieve best practice, maximise sample availability for positive
      societal outcomes such as teaching and research, and to comply with new
      regulations.

PMID- 18069535
TI  - Predicting driver from front passenger using only the postmortem pattern of
      injury following a motor vehicle collision.
AB  - This study aimed to establish whether post-mortem injury patterns can assist in
      distinguishing drivers from front seat passengers among victims of motor vehicle
      collisions without regard to collision type, vehicle type or if safety equipment
      had been used. Injuries sustained by 206 drivers and 91 front seat passengers
      were catalogued from post-mortem reports. Injuries were coded for the body
      region, depth and location of the injury. Statistical analysis was used to detect
      injuries capable of discriminating between driver and passenger. Drivers were
      more likely to sustain the following injuries: brain injury; fractures to the
      right femur, right posterior ribs, base of skull, right humerus and right
      shoulder; and superficial wounds at the right lateral and posterior thigh, right
      face, right and left anterior knee, right anterior shoulder, lateral right arm
      and forearm and left anterior thigh. Front passengers were more vulnerable to
      splenic injury; fractures to the left posterior and anterior ribs, left shoulder
      and left femur; and superficial wounds at the left anterior shoulder region and
      left lateral neck. Linear discriminant analysis generated a model for predicting
      seating position based on the presence of injury to certain regions of the body;
      the overall predictive accuracy of the model was 69.3%. It was found that driver
      and front passenger fatalities receive different injury patterns from motor
      vehicle collisions, regardless of collision type. A larger study is required to
      improve the predictive accuracy of this model and to ascertain its value to
      forensic medicine.

PMID- 18069536
TI  - Are Asians at greater risk of compulsory psychiatric admission than Caucasians in
      the acute general adult setting?
AB  - Patients of African-Caribbean origin appear to be at greater risk of compulsory
      admission to psychiatric hospitals in the United Kingdom but it is not clear
      whether this is the case for patients of Asian origin. Case notes and original
      sections papers were retrospectively reviewed over a one-year period in a
      psychiatric unit serving a large city in the UK. Caucasian and Asian patients
      were compared in terms of their representation in the population at risk and
      rates of detention under mental health legislation. Asian patients were
      significantly overrepresented as in-patients, were more likely to be detained at
      admission and more likely to be detained under longer-term powers during their
      stay. Asian patients may be similarly over-represented in the psychiatric in
      patient population and more likely to be detained under mental health legislation
      than African-Caribbean patients in the UK. Future studies and service providers
      may need to consider patients of Asian origin as having different mental health
      needs.

PMID- 18069537
TI  - Analysis of 756 cases of sexual assault in Tours (France): medico-legal findings
      and judicial outcomes.
AB  - We describe the medico-legal findings in a population of sexual assault cases
      assessed in an urban French referral centre, analyse the subsequent legal
      dispositions in each case and determine whether the characteristics of the
      assault and the medico-legal findings were associated with conviction of the
      assailant. We performed a retrospective study of medicolegal reports in all the
      sexual assault cases reported in Tours (France) during a seven-year period. We
      defined two groups of victims: children under 15 years old and victims aged 15
      years or more. Legal outcomes were obtained from courtroom proceedings. The
      relationship between the outcomes and the circumstances of the case was analyzed
      by logistic regression. We enrolled a total of 756 cases during the study period.
      The mean age of the study population was 16.5 years and 68.3% of the cases
      involved children under 15 years old. In 57% of these cases, the assailant was a
      family member. 31.7% of all the victims were aged 15 years or more. The assailant
      was an acquaintance of the victim in 62.2% of the cases. Drug-facilitated assault
      was suspected in 2.9% of the cases. In 46.2% of the cases, formal criminal
      charges were not filed due to insufficient evidence; 36.3% of the assailants were
      convicted. Examination at the request of the police authorities and previous
      acquaintance of the assailant by the victim were significantly associated with
      conviction. Allegations of penetration, the presence of general body trauma and
      the presence of genital trauma were not necessarily associated with conviction.
      Medical examiners need to be circumspect when they record non-medical variables.
      Physical evidence of trauma was neither predictive nor essential for conviction.
      Successful prosecution depends on the quality of the testimony provided by the
      victim.

PMID- 18069538
TI  - Referrals to the Glasgow sheriff court liaison scheme since the introduction of
      referral criteria.
AB  - This study is an audit of a court liaison scheme operating in Glasgow sheriff
      court. It represents a follow-on of previous work after the introduction of
      referral criteria to delineate more closely the appropriate population to be
      seen. Results were compared with the previous audit. The total number of
      referrals decreased by 66%, however, the proportion with a psychotic illness
      increased to 33%. A high referral rate of prisoners with addictions continued,
      although the service was not primarily designed for them. Fewer patients with no
      psychiatric diagnosis were referred to the scheme. Outcomes were, however,
      similar with approximately the same admission rate to hospital. The introduction
      of criteria appears to have reduced the numbers of inappropriate referrals
      without excluding the population with serious mental disorder. The introduction
      of referral criteria seems to have been beneficial to the scheme. The scheme has
      since changed again and so there may be benefit for a further audit to monitor
      the continuing appropriateness of referrals. The provision of specific
      interventions targeting prisoners with addictions is also supported by this
      audit.

PMID- 18069539
TI  - Pattern of skeletal injuries in cases of falls from a height.
AB  - Differentiating the injuries exclusively due to falls from a height is difficult
      if no proper history is provided. Some clinical studies and case reports have
      been published on the subject, but an autopsy-based approach to the subject is
      missing in the literature of recent decades. A retrospective study was carried
      out on 80 cases of fatal falls from a height brought for autopsy. In selected
      instances police reports, suicide notes, medical records and scene photographs
      were reviewed. The principal aim was to look for a pattern of skeletal injuries
      formed as a result of falls from a height. The majority of the victims were male,
      aged between 20-30 years and labourers by occupation. Most of them fell from a
      height of 0-10 feet. The head is the most vulnerable structure with fractures of
      the vertex being common. As the height of falls increases, fractures of the ribs
      and sternum are also found. Finally, it is concluded that falls on the head are
      more likely and the most fatal of all. However, it cannot be taken as a sole
      indicator of the manner of death. Risk assessment should be carried out before
      any work at a height is undertaken.

PMID- 18069540
TI  - A comparative analysis of suicide and parasuicide.
AB  - A prospective study was conducted to analyse the spectrum of suicide attempters
      and completers at Kasturba Hospital, Manipal, India, over a period of three years
      (January 2001 to December 2004). The present study comprised a total sample
      population of 246 cases, of whom 90 died and 156 survived the attempt (1:1.73).
      Men outnumbered women in the deceased group and women surpassed men in the
      survivor group. The mean age for the deceased group was 42 years compared with 30
      years for the survivor group. Prior attempted suicide in the deceased group was
      6.6%. Eighty-three percent of the total population studied opted for 'chemical
      methods', where insecticides topped the list (64.6%) in both the deceased and the
      survivor group. Among those who preferred 'physical methods', 50% died and 50%
      survived. In the current study, 17% of the subjects had received a psychiatric
      consultation, of whom 91.3% were diagnosed in the spectrum of 'depressive
      disorders.' Knowledge about the legalities of suicide was lacking in 65% of
      victims and their kin.

PMID- 18069541
TI  - HIV infection among victims of sexual assault using condoms and other
      contraceptive methods: a comparative study.
AB  - The aim was to study the incidence of HIV among victims of sexual assault who
      have been using condoms and other contraceptive methods. Retrospective review of
      cases who presented to the Sinawe Centre following sexual assault was carried
      out. There were 157 sexually active cases between 17 and 49 years of age in the
      study group. The mean age of the victims was 22.7 years. All had practised some
      form of contraception. One had a tubal ligation, 65 (41.8%) had used condoms, 22
      (13.9%) oral contraceptives (OC), 55 (35.4%) injectables, and 12 (7.6%) both
      barrier method and hormonal. The highest number (28 -17.7%) of HIV positive cases
      were in the age group of 17 to 26 years. A total of 42 (27%) were HIV positive of
      whom 26 (16.6%) had only used condoms, ten (6.4%) had used OCs and injectables,
      and six (3.8%) used both hormonal and barrier methods. In conclusion, HIV
      prevalence is commoner among condom users.

PMID- 18069542
TI  - Suicide by homemade firearm: a case report.
AB  - This paper presents a unique case of suicide committed by a homemade firearm. A
      56-year-old man shot himself with a homemade firearm capable of accommodating and
      firing 8 mm rifle ammunition. The victim put the muzzle of the weapon on the
      right side of his skull and died immediately after firing. The overall and barrel
      lengths of the firearm were 29.5cm and 17.5cm respectively. The barrel was
      oversized for the 8 mm rifle bullet having an average muzzle and breech diameter
      of .423in. (9.53 mm) and .489in. (11.02 mm) respectively. The cartridge case
      recovered from the chamber was swollen due to the oversized non-standard chamber.
      The bullet recovered was deformed and elongated. The injury and bullet track
      present on the victim's head were unique in nature. With respect to the weapon
      and ammunition, this study represents an unusual suicide. The findings will be
      helpful to the medicolegal experts, forensic scientists and pathologists.

PMID- 18069543
TI  - Traumatic heart perforation by a D5 osteophyte: a case report.
AB  - Osteophytes are bony outgrowths usually found in the context of osteoarthritis
      and diffuse idiopathic skeletal hyperostosis (DISH). Even if they are usually
      asymptomatic, they may present with complications such as spinal stenosis,
      myelopathy and radiculopathy. We here present the case of a 56-year-old woman
      found dead from a homicidal traumatic heart perforation by a D5 osteophyte.

PMID- 18069544
TI  - Two entrances, one exit--an atypical shotgun injury: a case report.
AB  - Firearm-related injuries are a major problem worldwide and one of the central
      issues in forensic pathology. An atypical appearance of a gunshot wound can
      create surgical or medico-legal diagnostic problems. We report a case of a
      homicidal shotgun fatality with an unusual trajectory of pellets in the body. Two
      large pellets perforated the anterior chest wall near to each other but made
      their exit through a common wound in the back. Our report describes the results
      of the medico-legal investigation and discusses problems related to examination
      of firearm wounds.

PMID- 18069545
TI  - An unusual suicide with parenteral copper sulphate poisoning: a case report.
AB  - A 22-year-old unmarried, male painter was found by neighbouring shopkeepers to be
      rolling on the ground inside his shop due to severe abdominal pain. The man had
      tried to commit suicide by intravenously injecting a solution of copper sulphate,
      used as an antifouling agent in paints. He was taken to the local hospital with
      severe epigastric pain, vomiting and diarrhoea. His condition worsened after
      three days and he was transferred to the All India Institute of Medical Sciences,
      New Delhi, but the victim died on his way to the hospital. His relatives and
      neighbours confirmed that he had recently been suffering from depression.

PMID- 18069546
TI  - [Studies on prevalence and control of several common chronic diseases among
      Beijing adults in 2005].
AB  - OBJECTIVE: To understand the prevalence and control of several common chronic
      disease in Beijing adults. METHODS: 16,658 adult residents were randomly selected
      with stratified multi-stage cluster sampling method. Each participant was invited
      to receive a set of standardized questionnaire, physical examinations and
      laboratory tests. RESULTS: Data showed that the prevalence, awareness, treatment
      and the rate of control on hypertension among the adults in Beijing were 29.1%,
      49.3%, 42.3% and 10.6% respectively. The counterparts of diabetes mellitus were
      8.8%, 56.7%, 50.0% and 15.0%. The four corresponding figures for dyslipidemia
      were 33.2%, 31.1%, 13.0% and 4.3%, respectively. 22.9% of the Beijing adults had
      metabolic syndrome including 8.1 per thousand suffering from myocardial
      infarction and 18.4 per thousand from stroke. Except for diabetes, all the
      chronic diseases had higher prevalence rate in rural area than in urban area,
      according to the findings under our study. Postmenopausal women were more
      susceptible to chronic disease than men. CONCLUSION: The prevalence rate of
      chronic disease in Beijing was still high. The prevalence rate in rural area had
      exceeded the level in urban area. Adjustment and attention should be made
      according to the prevalence features and weakness existed in present chronic
      disease control strategy.

PMID- 18069547
TI  - [The prevalence of diabetes in children and adolescents of Beijing].
AB  - OBJECTIVE: To study the prevalence of Diabetes mellitus (DM) in children and
      adolescents and to describe the characteristics on age, gender and district
      distribution of schoolchildren, in Beijing. METHODS: A cross-sectional screening
      program the fasting capillary blood glucose (FCBG) was carried out in 19,593
      schoolchildren in 7 areas of Beijing from March to October, 2004. According to
      the WHO diagnostic criteria: DM was set as FCBG < or = 6.1 mmol/L, impaired
      fasting glucose (IFG) was set as 5.6 mmol/L < or = FCBG < 6.1 mmol/L. RESULTS:
      The total aggregate age-adjusted prevalence rates of DM and IFG were 5.7 per
      thousand and 13.5 per thousand, respectively. The prevalence rates of DM and IFG
      in males were significantly higher than that in females (7.7 per thousand vs. 3.6
      per thousand and 26.8 per thousand vs. 11.3 per thousand. DM X2 = 12.27, P =
      0.0005; IFG X2 =47.29, P = 0.0000). Among seven districts, East District had the
      highest prevalence rates of DM and IFG, 8.9 per thousand and 27.4 per thousand
      (companied high obesity 28.68%) while Ping-Gu District having the lowest ones as
      2.0 per thousand and 7.5 per thousand (obese 12.75%) respectively (X2 = 13.75,
      and X2 = 32.65, P = 0.0002 and P < 0.0001). The DM prevalence rates between
      districts ranged from 2.0 per thousand to 8.9 per thousand, X2 = 18.94, P = 0.004
      and the IFG prevalence of districts ranged from 7.5 per thousand to 27.4 per
      thousand (X2 = 52.05, P < 0.0001). The prevalence rates of DM among different age
      groups increased with age, with the highest prevalence of IFG on the 10-14 age
      group. Among boys, the highest prevalence rates of DM and IFG fell in the 15-18
      and 10-14 age groups respectively while the highest prevalence rates on both DM
      and IFG among girls were in the same age group 10-14. CONCLUSION: The high
      prevalence rates on DM and IFG were seen in Beijing and showed significant
      discrimination on age, gender and district distribution. More developed urban
      district and males had a higher prevalence, companied by higher obesity
      prevalence. Age seemed to be a high risk factor on DM for boys while the puberty
      development seemed a high risk factor for girls.

PMID- 18069548
TI  - [Study on the body mass index reference norm for defining overweight and obesity
      in school-age children and adolecents with Uygur and Han ethnic backgrounds in
      Urumqi].
AB  - OBJECTIVE: To construct and compare the body mass index (BMI) cutoff points for
      defining overweight and obesity in school-age children and youths with Uygur and
      Han ethnic backgrounds in Xinjiang, China. METHODS: A total number of 9146 boys
      and girls in Urumqi, Xinjiang, aged 7-18 years, were recruited by stratifying and
      clustering sampling from April to June 2004. Demographic and anthropometric data,
      including body weight and standing height, were collected. Questionnaires and
      standard methods were used and BMI was calculated by weight/height2. BMI centile
      curves with age were drawn according to gender and ethnicity, using LMS software
      (Tim cole and Huiqi Pan) which were making the centile curves passing through 25
      kg/m2 and 30 kg/m2, and 24 kg/m2 and 28 kg/m2 at age of 18 for overweight and
      obesity respectively. RESULTS: The age and sex specific BMI centile curves were
      drawn for children with Uygur and Han ethnicities. Data showed that BMI increased
      with age. The centile of BMI curves, P94.46 and P99.58 for Uygur boys, P92.44 and
      P99.64 for Uygur girls, P85.05 and P97.26 for Han boys, P90.92 and P99.03 for Han
      girls, which passing through 25 kg/m2 and 30 kg/m2 by IOTF recommendation at age
      18, were constructed. Under the basis of WGOC recommendation, the points that
      passing through 24 kg/m2 and 28 kg/m2 at age 18 were P90.54 and P98.86 for uygur
      boys, P86.96 and P98.77 for uygur girls, P78.98 and P94.72 for Han boys, P86.15
      and P97.56 for Han girls. The BMI cutoff points for defining overweight and
      obesity were suggested. CONCLUSION: To the best of our knowledge, the present
      study established the BMI cutoff points for Uygur ethnic school-aged children and
      youths for identifying overweight and obesity. There was ethnic difference in the
      BMI distribution with age. We recommended using the BMI cutoff points proposed by
      the current study to identify those overweight and obese children in Urumqi.

PMID- 18069549
TI  - [Related factors on quality of life in 291 outpatient adults with epilepsy].
AB  - OBJECTIVE: To assess and explore the quality of life and related factors among
      291 outpatient adults with epilepsy. METHODS: From July, 2005 to July, 2006,
      eligible outpatient epilepsy in a hospital was evaluated by the scale on quality
      of life in epilepsy-31 (Chinese version). RESULTS: The total scores of quality of
      life was low (56.46 +/- 16.58). The scores of quality of life in each item were
      as follows: seizure worry (45.01 +/- 25.25); overall quality of life (56. 12 +/-
      16.37); emotional well-being (59.35 +/- 19.56); cognitive function (58.58 +/-
      22.41); energy/fatigue (59.12 +/- 18.98); medication effects (40.45 +/- 24.44)
      and social function (53.00 +/- 26.36). The quality of life of patients with
      different education background, drug intake and side effects was different
      significantly (P < 0.05). Data on Multi-linear regression showed that education
      background, side effects would affect the quality of life. CONCLUSION: The
      quality of life of outpatient adults with epilepsy was low with education
      background, while side effects and drugs intake might serve as important factors
      affecting the quality of life with epilepsy.

PMID- 18069550
TI  - [Study on the epidemiological characteristics of rubella from 1990-2006 in
      Shanghai].
AB  - OBJECTIVE: This paper analyzed the epidemiological characteristics of rubella in
      Shanghai from 1990 to 2006. METHODS: Descriptive epidemiological study was
      applied to analyze the cases from infectious diseases reported system on rubella
      during 1990-2006 in Shanghai. Excel was used for data analysis. RESULTS: The
      reported rubella incidence rate in Shanghai was 0.15-451.57 per 100,000 during
      the period from 1990 to 2006. A rubella epidemic happened in 1993, with the
      number of reported cases as 58,104. The year 1998 was the low year on rubella
      with only 19 reported cases. In the years without rubella vaccine (RV), that was,
      from 1990 to 1994, the annual reported incidence rate of rubella was 93 per
      100,000, and there was a distinct characteristic of seasonal difference, with
      peak in march through June each year. Rubella cases mostly affected children aged
      5-9 and adolescent of 10-14 years old. Since the wide use of RV in Shanghai since
      1995, RV and measles, mumps, rubella (MMR) had been widely accepted by parents.
      The vaccination rate of MMR reached up to 85 percent. The incidence of rubella
      was descending as year went by. The annual reported cases were less than 100
      since then (with exception in the year 1995). Local outbreaks were further
      reduced and the age group structure had also changed since the adoption of RV.
      Patients with RV fallen into the age group of 0-4 were increasing quickly,
      accounting for 21.00% percent of all the patients and the age become older.
      31.62% of the patients fell into 20 years of age and above. During 1995-2006, the
      incidence rates of rubella in age 25-29 and 30-34 were both much higher than that
      in the year without vaccine. CONCLUSION: The trend of older age among patients
      wilt Rubella increased the risk on fertile woman and geting congenital rebella
      syndrome.

PMID- 18069551
TI  - [Study on genotyping of Mycobacterium leprae and families with multi-cases].
AB  - OBJECTIVE: Multiple locus variable number-tandem repeat (VNTR) analysis (MLVA)
      had been proposed as a means of strain typing for tracking of source and studying
      the transmission chain of pathogens. However, empirical data for a defined
      population from scale and duration were lacking for studying the transmission
      chain of leprosy. METHODS: MLVA on 7 VNTR loci was applied to the strain typing
      on prevalent Mycobacterium leprae isolates collected from Qiubei county, Yunnan
      province during 2002-2006 in the study on the relationship between geographic
      distribution and genotypes of M. leprae. The strain typing, combined with
      conventional epidemiological investigation was performed to trace the
      transmission chain. RESULTS: (1) Phylogenetic analyses through application of
      PAUP 4.0, The M. leprae were grouped into A, B, C, D and E strains according to
      the allelic range 9, 11-13, 15-26 and > 26 on the GTA9 locus. The strains with 9
      copies on GTA9 locus, was named A. (2) Genotypes of strains from the five multi
      case families located at North and North-West parts were similar and belonged to
      A strains. VNTR patterns of intra-family were identical or similar but not
      identical inter-family. (3) Not only A cluster appeared higher proportion in
      total isolates but also distributes cluster, indicating ongoing transmission from
      recent findings. CONCLUSION: VNTR strain typing was suitable to trace the short
      chain of transmission in both small area and intra-families. Multi-case families
      might constitute epidemic foci and source of M. leprae in villages, causing the
      predominant strain or cluster which tends to be those identified in multi-case
      families and resulted in the spreading of leprosy. A long-term study was underway
      to reveal whether A strain was predominant strain and to observe the evolution of
      M. leprae in this spatially and temporally defined endemic population.

PMID- 18069552
TI  - [Comprehensive evaluation on the potential risk for HIV infection in 12 villages
      with a history of former paid blood donation].
AB  - OBJECTIVE: To learn the potential risk for human immunodeficiency virus (HIV)
      infection in 12 villages with a history of former paid blood donation, and to
      provide different measures for HIV/AIDS prevention and control. METHODS: Seven
      indexes were selected, including HIV sero-prevalence rates, hepatitis C virus
      (HCV) sero-prevalence rates, HIV/AIDS KAB (knowledge, attitude and belief),
      proportion of paid blood/plasma donation, risks on related behavioral information
      on sex and HIV/AIDS infections. Rank Sum Ratio (RSR) was performed to
      synthetically evaluate the potential risk of HIV infection in those 12 selected
      villages. RESULTS: According to the results of evaluation by 18 experts, weight
      coefficient of HIV sero-prevalence rate was the highest (0.28), and HIV/AIDS KAB
      the lowest (0.09) among the seven indexes. The results of comprehensive
      evaluation with RSR showed that the villages coded 01 and 02 belonged to higher
      level of potential risk of HIV infection, villages 09, 12, 05, 10 and 03 were at
      medium level while villages 04, 06, 08, 07 and 11 were at low level. CONCLUSION:
      The level of potential risk for HIV infection was different in 12 villages with a
      history of former paid blood donation. Different measures of HIV/AIDS prevision
      and control should be performed according to the potential risk level for HIV
      infection of the 12 villages.

PMID- 18069553
TI  - [Study on the variations of hepatitis B virus status among people having received
      hepatitis B vaccine].
AB  - OBJECTIVE: To study the epidemiological pattern and trends of hepatitis B virus
      (HBV) in the area where people had been immunized by HBV vaccine for long time.
      METHODS: Through cluster sampling and cross-sectional study, relative information
      and blood samples from people in Long-an county by families were collected.
      Signals of HBV infection were tested by solid-phase reverse immunosorbent test.
      RESULTS: (1) The average HBsAg positive rate was 7.5% with anti-HBs as 44.5 %,
      and anti-HBc as 47.8%. The positive rates of HBsAg and anti-HBc among 0-19 year
      olds were lower than those of > or = 20 year-olds. (2) The positive rates of
      HBsAg, anti-HBc and HBV infection among HBV vaccine immunized group were 2.8%,
      12.0% and 12.5% respectively, comparing with which among the un-immunized group
      as 10.2%, 69.8% and 71.2% respectively. (3) The HBsAg positive rate of male was
      higher than the female's but with no significant difference of anti-HBs and anti
      HBc between different sexes. (4) The average HBsAg positive rate of 0-19 years
      old group was only 2.4%, while that of 20-30 years old group was 13.6%-17.7% and
      dropped from 60 years old group and on. The anti-HBs positive rate of 0-19 years
      old people started to drop significantly by age. The anti-HBs and anti-HBc
      positive rates of > or = 20 years people were showing a rising trend by ages.
      CONCLUSION: It seemed obviously that the HBV epidemiological patterns had changed
      after HBV vaccine had been universally used for long time in newborns. The age
      peak of infection had been pushed backward for nearly 20 years. It had been
      proved that the HBV vaccine immunization program had obtained excellent efficacy.

PMID- 18069554
TI  - [Study on an outbreak of echovirus type 6 of meningitis in Liu'an city, Anhui
      province].
AB  - OBJECTIVE: To understand the epidemiological, clinical and etiological
      characteristics of an Echovirus type 6 meningitis outbreak in Jinzhai county,
      Liu'an city in Anhui, and to find out the proper way in controlling the aseptic
      meningitis outbreak. METHODS: A surveillance system for aseptic meningitis was
      established in Jinzhai to confirm the case definition. Stool or cerebrospinal
      fluid (CSF) specimens from some cases were collected for entero-viruses isolation
      and identification. Case-control study was conducted. The case group involved
      patients while the controls would include: patients' classmate with same gender
      and the age difference was not over one year. Neutralization antibody in serum
      specimens were collected and tested in cases and in healthy people. RESULTS: 105
      cases were distributed in 17 of the 30 towns in Jinzhai county while 41.0% of the
      cases were in Banzhuyuan town with an incidence rate of 203/10(5). Cases were
      clustered by school and classroom with age ranging from 3 to 15 years old and the
      highest as 10.9/10(5) in the 6 to 10 group. The incidence in males was 24.2/10(5)
      compared to 8.4/10(5) in females. The main clinic characteristics of cases were:
      fever, headache and vomiting. Echovirus type 6 from 25 of the 72 CSF samples
      (35%) was isolated. When comparing the cases group with control group, the OR of
      drinking home-made beverages was 4.1 (95% CI: 1.4-12.0), especially the beverages
      sacked by plastic bag: 3.3 (95% CI: 1.3-8.8). 6 out of 7 workers engaging in
      producing home-made beverages were detected to have carried Echovirus type 6 from
      their stool specimens. The Echovirus type 6 neutralization antibody positive rate
      in cases (73.5%) was significantly higher than that in 100 healthy people (46.0%)
      (X2 = 12. 526, P = 0.000). CONCLUSION: This episode of meningitis outbreak was
      caused by Echovirus type 6. The proportion of drinking home-made beverages,
      especially the beverages sacked by plastic bag in cases group was higher than in
      control group.

PMID- 18069555
TI  - [Study on the epidemiologic characteristics of norovirus infection in Beijing].
AB  - OBJECTIVE: To investigate the epidemiological characteristics of norovirus
      infection in Beijing. METHODS: Both outbreaks and sporadic cases of acute
      gastroenteritis were studied through questionnaires while the stools of patients
      were collected. Noroviruses were detected by ELISA or RT-PCR, and PCR products
      were cloned and sequenced. RESULTS: Eight outbreaks were reported between
      November 2006 and March 2007, which were confirmed as nosocomial infections. A
      total of 158 positive cases were detected among 409 sporadic cases of acute virus
      gastroenteritis with a positive rate of 38.63%. The highest positive rate
      (55.00%) was found in group aged from 40 to 44, while the lowest positive rate
      (21.74%) fell into groups aged from 55 to 59. The positive cases aged from 6
      months to 91 years with the mean age of 40 years old including 84 males and 74
      females. Data from sequence analysis showed that norovirus epidemic strains
      helonged to the GII/4 variants in Beijing, which were almost identical to the
      variants causing epidemics both in the Netherlands and in Japan. CONCLUSION:
      Norovirus was important, causing virus-borne diarrhea between 2006 and 2007 in
      Beijing, and the epidemic strains were consistent with those isolated from both
      the Netherlands and Japan in 2006.

PMID- 18069556
TI  - [A preliminary study on molecular characteristics of noroviruses detected in
      Beijing].
AB  - OBJECTIVE: To investigate the molecular characteristics of noroviruses detected
      in Beijing. METHODS: From January to March 2007, cases from both outbreaks and
      sporadic episodes of acute nonbacterial gastroenteritis were investigated in
      Beijing, and the fecal specimens of the patients were collected. Noroviruses were
      detected by a reverse transcription polymerase chain reaction (RT-PCR), and then
      the PCR products were cloned and sequenced. RESULTS: A total of 27 positive cases
      were identified as caused by noroviruses among the 38 patients with acute viral
      gastroenteritis, and four PCR products were randomly selected for further studies
      on sequencing. When comparing to the nucleotide sequences of norovirus reference
      strains from GenBank, the highest homology was found between the four isolates
      and the norovirus GII/4 strains. The four strains isolated from Beijing were
      almost identical to the GII/4 variants that causing epidemics in the Netherlands
      and in Japan with the homology of 97.8%-98.5% and 95.2%-95.9%, respectively.
      Phylogenetic analysis revealed that the four isolates were located at the same
      branch as the norovirus GII/4 variants in Netherlands and Japan. CONCLUSION: New
      norovirus GII/4 variants were found in Beijing, and data from sequence analysis
      showed that the four isolates and the epidemic strains isolated from both the
      Netherlands and Japan in 2006 belonged to the same group of norovirus GII/4.

PMID- 18069557
TI  - [Clinical manifestations of norovirus gastroenteritis in infants and children].
AB  - OBJECTIVE: To study the clinical manifestations for norovirus gastroenteritis in
      infants and young children. METHODS: Stool specimens were collected from infants
      and children with acute diarrhea who visited the affiliated Children's Hospital
      to Capital Institute of Pediatrics from January 2002 to December 2006. Enzyme
      linked immunosorbent assay (ELISA) was used to detect human norovirus antigen in
      stool specimens and polyacrylamide gel electrophoresis (PAGE) was performed to
      detect rotavirus genome. RESULTS: Out of the 318 specimens under testing, 79
      showed positive for norovirus antigen, with a positive rate of 24.8% (79/318).
      Among those positive specimens, 48(48/79, 60.8%) were detected in October to
      December, suggesting the seasonal preference of the virus. Most of the positive
      specimens (91.2%) were from those under 2 years of age. Rotavirus genome were
      detected from 16 out of 79 norovirus positive specimens (16/79, 20.3%),
      indicating those patients were co-infected by these two viruses. There was
      significant difference found in the severity of fever but not in the frequencies
      of diarrhea between rotavirus and norovirus co-infection group and noroviral
      infection group. Fourteen out of 79 norovirus positive patients were admitted to
      hospitals under the diagnosis other than gastroenteritis but started to develop
      symptoms of diarrhea between 1 to 11 days after hospitalization. CONCLUSION:
      Norovirus seemed one of the most important pathogens for acute diarrhea among
      infants and young children and could cause nosocomial infectious gastroenteritis.

PMID- 18069558
TI  - [Surveillance on human metapneumovirus in infants and children with acute
      respiratory infections in Beijing, from 2004 to 2006].
AB  - OBJECTIVE: To understand the prevalence of human metapneumovirus (hMPV) infection
      in infants and young children in Beijing, China. METHODS: Gene fragment from hMPV
      was amplified by reverse transcription-polymerase chain reaction (RT-PCR) with
      the primer pair located on the membrane (M) encoding gene. RNAs were extracted by
      Trizol from 3330 specimens collected from outpatients and inpatients with acute
      respiratory infections and visited the affiliated Children's Hospital from July
      2004 to June 2006. These samples had been tested for conventional respiratory
      viruses including RSV, influenza A and B, parainfluenza I , II , III and
      adenovirus by indirect immunofluoresence assay as well as virus isolation before
      RT-PCR for hMPV. RESULTS: Out of the 3330 clinical samples, 110 (3.3%) were found
      positive to hMPV. The ratio of male to female among those positive to hMPV was
      1.5:1. Fifty-one out of 110 positive (46.4%, 51/110) specimens on hMPV were from
      children under one year olds, 13 (11.8%,13/ 110) were from 1 to 2 year olds, 37
      (33.6%, 37/110) were from 2 to 5 years of age, and 9 (8.2%, 9/110) among children
      over 5 years of age. hMPV was associated with: pneumonia in 44.5% (49/110) of the
      cases ; upper respiratory infections in 22.7% (25/110); bronchiolitis in 10.9%
      (12/110); and bronchitis in 7.3% (8/110). hMPV was detected almost in every month
      from July 2004 to June 2005 in sporadic cases whereas a peak was noticed in April
      2006 during the period from July 2005 to June 2006. Among 110 positive samples, 6
      (5.5%) were also positive for other viruses including 3 as Influenza B, 2 as RSV
      and 1 as Parainfluenza 3, suggesting that these children were co-infected with
      hMPV and other respiratory viruses. The peak of hMPV prevalence did not overlap
      with that of RSV during this period. CONCLUSION: Our findings suggested that hMPV
      had been one of the important agents causing acute respiratory infections
      especially severe lower respiratory infections like pneumonia and bronchiolitis
      in pediatric patients in Beijing. Infants and young children under two years of
      age seemed to be more susceptible to hMPV.

PMID- 18069559
TI  - [Study on the status of human rhinovirus infections in infants and young children
      with acute respiratory infections in Beijing, from 2002 to 2006].
AB  - OBJECTIVE: To understand the relationship between human rhinovirus (HRV) and
      acute respiratory infections in infants and young children in Beijing. METHODS:
      Throat swab/nasopharyngeal aspirates were collected from 3292 infants and young
      children with acute respiratory tract infections in Beijing from November 2002 to
      November 2006. Primers derived from the highly conserved 5'-noncoding region of
      human rhinovirus were used to detect HRV from clinical specimens by nested RT-PCR
      for which the sensitivity and specificity had been determined previously.
      RESULTS: Out of these 3292 specimens, 507 were (15.4%, 507/3292) HRV positive
      with RT-PCR method. HRV were detected from 220 out of 1315 outpatients and 287
      out of 1977 inpatients with positive rates as 16.7% and 14.5% respectively. HRV
      was detected from 50.0% (8/16) of the patients with pharyngitis. Among 280
      specimens collected from patients with acute bronchitis, 43 (15.4%) were HRV
      positive, including 14 from 80 patients with wheezy bronchitis (17.5%). High
      positive rates were also found in specimens from patients with pneumonia (12.6%,
      150/1189), bronchiolitis (16.0%, 42/262) and asthma (12.8%, 10/78). In 53
      patients with initial diagnosis as hematic disease or other complicate
      respiratory infections, 14 were HRV (26.4%, 14/53) positive. As for the seasonal
      distribution, HRV were detected in most of the months during thie period of
      research. The highest positive rate of HRV in each year fell in September
      (32.6%), February (24.2%) of 2004, February of 2005 (35.3%) and March (31.3%)
      from 2003 to 2006, respectively. Among these HRV positive patients, 44.8% were
      under 1 year of age (227/507), 15.4% (78/507) were 1 to 2 years old and 12.4%
      (63/507) were 2 to 3 years old. CONCLUSION: HRV was associated with acute upper
      respiratory infections and lower respiratory infections including bronchitis,
      pneumonia and bronchiolitis in pediatric patients. Patients with lower immunity
      such as those with hematic diseases, were more susceptible to be infected by HRV.
      HRV could be detected in all age groups in this study, but the positive rates
      were decreasing with the increase of patients' age. Infants under 1 year of age
      seemed to be more likely to get HRV infection.

PMID- 18069560
TI  - [Detection of adenovirus-IgM antibody in children hospitalized with lower
      respiratory tract infection in Beijing Children's Hospital].
AB  - OBJECTIVE: To explore the characteristics of adenovirus (ADV) infection in
      children hospitalized with lower respiratory tract infection (LRTI) in Beijing
      Children's Hospital. METHODS: One thousand and forty-six children hospitalized
      with pneumonia or bronchitis in Beijing Children's Hospital from October 2004 to
      December 2005, were enrolled in our study. Serum samples were collected from each
      patient and detected for ADV-IgM by indirect ELISA, excluding those serum samples
      which were positive for any of the antibodies as CMV, EBV, HSV, Enterovirus.
      RESULTS: Eighty-seven (11.8%, 87/738) were positive for ADV-IgM in 738 cases
      which were negative on other pathogen. The percentage of LRTI with ADV infection
      was 8.3% (87/1046) during the period. Thirty-two cases were younger than 1 year
      of age while 42 cases were between 1-6 and 13 cases were older than 6 years old.
      The ratio of male to female was 1.4:1. ADV infection occurred throughout the year
      and relatively frequent in winter and spring. CONCLUSION: ADV was one of the most
      important viral pathogens on lower respiratory tract infections in children under
      5 year olds. Children aged from 6 months to 3-years were susceptible to ADV
      infection.

PMID- 18069561
TI  - [Using direct enzyme linked immunosorbent assay for the detection of IgG antibody
      on Bartonella henselae among healthy people in Changping, Beijing].
AB  - OBJECTIVE: To detect Bartonella henselae IgG antibody among healthy people in
      Changping, Beijing. METHODS: Using indirect enzyme linked immunosorbent assay
      (ELISA) and immunofluorescence antibody assay (IFA) to detect IgG antibody of
      Bartonella henselae among human beings. RESULTS: The sensitivity and specificity
      of ELISA were 70.6% and 91.6% respectively, with the positive predictive value of
      serological test as 82.2%, and the negative predictive value as 84.9%, based on
      results of IFA. The positive rate was 34.5% among 357 healthy people on indirect
      ELISA but was 35.6% among 239 people with IFA. CONCLUSION: The results indicated
      that the indirect ELISA was a very quick, sensitive and available method for
      detecting Bartonella henselae in human beings, as well as a high positive percent
      age of Bartonella henselae among the healthy people of Changping Beijing.

PMID- 18069562
TI  - [Study on the recombinant expression of Hantaan virus protein N and the
      establishment and application of rNP-IgM direct capture ELISA].
AB  - OBJECTIVE: To clone the gene encoding nucleocapsid protein (NP) of hantavirus
      strain Z10 (HV-Z10), to construct its prokaryotic expression system as well as to
      establish a rNP-IgM direct capture ELISA based on HRP-labeled recombinant NP
      (rNP), in order to detect serum samples of patients suffering from hemorrhagic
      fever with renal syndrome (HFRS) and to evaluate the effects of detection.
      METHODS: Gene encoding NP of strain HV-Z10 was amplified by PCR and then its
      prokaryotic expression system pET28a-Z10N-E. coli BL21DE3 was constructed, using
      routine genetic engineering method. SDS-PAGE was applied to measure the
      expression of rNP and ion-exchange plus Ni-NTA-affinity chromatography was
      performed to purify the recombinant product. Western blot assay was used to
      determine the specific immuno-reactivity of rNP while HRP-labeled rNP-IgM direct
      capture ELISA was established to detect the serum samples from 95 cases of
      confirmed HFRS patients. The detection effect was compared with that by routine
      HV-IgM indirect capture ELISA method. RESULTS: pET28a-Z10N-E. coli BL21DE3 was
      able to express rNP with high efficiency. The purified rNP only showed a single
      protein fragment in the gel after SDS-PAGE. HV-IgG could efficiently recognize
      rNP and hybridize with the recombinant protein. 94.73% (90/95) of HFRS patients'
      serum samples were positively confirmed by rNP-IgM direct capture ELISA, while a
      positive rate of 92.63% (88/95) in the same samples was confirmed by HV-IgM
      indirect capture ELISA. The distributions of A450 values of the serum samples
      detected by the two IgM capture ELISAs as well as the changes of the A450 mean
      values from several serum samples with different dilutions were similar.
      CONCLUSION: We successfully constructed a high efficient prokaryotic expression
      system of NP encoding gene of hantavirus strain HV-Z10. The rNP-IgM direct
      capture ELISA that established in this study could be used as a new serological
      test for HFRS diagnosis because of its simplicity, safety, with high sensitivity
      and specificity.

PMID- 18069563
TI  - [Rapid testing on drug susceptibility of Mycobacterium tuberculosis with nitrate
      reducrase assay].
AB  - OBJECTIVE: To establish a rapid method for testing drug sussceptibility on
      Mycobacterium tuberculosis. METHODS: Taking absolute Concentration method for
      drug susceptibility testing of M. tuberculosis as the "gold standard", we
      examined the drug-resistant of M. tuberculosis strain with nitrate reducrase
      assay (NRA) and the drug-resistant of M. tuberculosis germ in sputum with NRA.
      RESULTS: NRA and absolute concentration method was basically comparable with NRA
      susceptibility as 96.5% and the specificity was 100%, When comparing with
      traditional absolute concentration method, NRA could shorten the time about 3
      weeks. Using NRA to test the drug-resistant of M. tuberculosis germ in sputum,
      its susceptibility was more than 66.7% and specificity was 100%, within 10-20
      days. CONCLUSION: NRA could be used as a rapid drug susceptibility testing on M.
      tuberculosis.

PMID- 18069564
TI  - [Study on the prognostic factors of colorectal cancer and on suggested model for
      prediction].
AB  - OBJECTIVE: To explore the factors related to the prognosis of colorectal cancer
      (CRC) and to establish a prognostic model for evaluating the prognosis of the
      patients with CRC. METHODS: 370 cases with CRC were selected in the study and
      clinical/pathological factors were collected and patients were followed. Kaplan
      Meier method was used to calculate survival rate. Log-rank test and proportional
      hazards regression model (Cox model) were used for univariate and multivariate
      analysis. Log cumulative hazards function plot was used to test Cox model
      proportional-hazards assumption (PH assumption). Prognostic index (P1) was
      calculated based on the results of multivariate analysis. RESULTS: (1) One-year,
      three-year and five-year survival rates were 90.5%, 78.3% and 76.5% respectively.
      (2) Lymphatic metastasis, Duckes classification and therapeutic measure were
      independent prognostic factors of CRC and all passed PH assumption. (3) Patients
      with different PI were classified into 3 groups and there were significant
      differences noticed in survival rates (P < 0.001). (4) Individual survival rate
      was evaluated based on the prognostic Cox model and PI. CONCLUSION: Lymphatic
      metastasis, Duckes classification and therapeutic measure were independent
      prognostic factors of CRC. To test PH assumption of the factors, selection of Cox
      model was essential. Cox model and PI seemed to be available in predicting the
      long term survivrate of patients with CRC.

PMID- 18069565
TI  - [Evaluation on the highly active anti-retroviral therapy in 181 AIDS patients].
AB  - OBJECTIVE: To study the clinical effect under highly active anti-retroviral
      therapy (HAART) in AIDS patients and for improving the curative effect and
      prognosis. METHODS: Epidemiological method was used from five aspects to describe
      the post-treatment clinical symptoms of 181 AIDS patients in Suizhou, and to
      evaluate the change of virus load and immune function of 79 AIDS patients. Data
      was doubly recorded by Epi Data and database was set up by SPSS 13.0 for
      analysis. RESULTS: The effective powers of anomal-fever, cough, diarrhoea,
      lymphadenectasis, weight drop, erythra, mycotic infection were 81.39%, 85.00%,
      84.62%, 81.89%, 82.86%, 66.07% and 45.45% respectively. CD4+ T lymphocyte count
      rose obviously after treatment, with an averag of 276 x 10(6) cells/ml (65 x
      10(6)-824 x 10(6) cells/ml), an 129 x 10(6) cells/ml increase in three months and
      was 294 x 10(6) cells/ml (102 x 10(6)-750 x 10(6) cells/ml) in six months. The
      count change of CD4+ T lymphocyte between 3 months and 6 months did not show
      sigificant difference. The number of deaths among drug withdrawals was 14, with a
      case fatality rate as 29.79%; while the number of deaths among non-drug
      withdrawals was 3, with the case fatality rate as 2.24%. CONCLUSION: Results
      through this study showed that HAART could obviously improve the clinical symptom
      of AIDS patients, and to increase the number of virus load. Improving the
      compliance could also reduce the case fatality rate.

PMID- 18069566
TI  - [Evaluation on the indirect economic burden of stroke using combination of
      disability-adjusted life years and human capital method].
AB  - OBJECTIVE: Using the indirect economic burden of stroke in a rural population to
      develop rational allocation of future health resources, in Hanzhong area.
      METHODS: Cluster sampling which involved 53 natural villages with a total number
      of 75,000 people selected from the 'stroke monitoring base' of rural population
      was adopted in this study in the Hanzhong area. All of the 164 stroke cases were
      studied through a self-designed questionnaire. In calculating disability-adjusted
      life years (DALYs), fixed value was used in accordance with the value of GBD. The
      disability assessment was simplified in DALYs calculation and modified Barthel's
      ADL was used in disability assessment of stroke patients. In indirect economic
      burden analysis, the human capital method combined with DALYs was adopted with
      the formula as: indirect economic burden = GNP per capita x DALYs x productivity
      weight. RESULTS: The total DALYs were 598.88, with an average DALY of stroke as
      3.65 per case. The total indirect economic burden of stroke patients in rural
      areas was 1,993,977.8 RMB and the average of indirect economic burden of stroke
      was 12,158.4 RMB per case with the largest seen in the 45-59 age group, accounted
      for 74.4%. CONCLUSION: In our study, the use of method in combining the human
      capital with DALYs was the first time being adopted in calculation of the
      indirect economic burden of stroke in rural population in China. The burden
      seemed to be much lower than literature cited from other countries. It was
      reasonable to evaluate indirect economic burden of stroke using method in
      integrating DALYs with human capital, but it was difficult to calculate the
      DALYs.

PMID- 18069567
TI  - Pitt-Easy Implant System: meeting patient and clinician satisfaction.

PMID- 18069568
TI  - [The University Hospital Center at Liege engaged from the 4 corners of the
      globe].

PMID- 18069569
TI  - [Image of the month. Fixed pigmented erythema, a cutaneous protest against a
      drug].

PMID- 18069570
TI  - [How I treat... An hepatocellular carcinoma: role of selective internal radiation
      therapy with intra-arterial iodine-131].
AB  - Hepatocellular carcinoma is a frequent disease, of poor prognosis. Its evolution
      is often fast and fatal. A majority of patients die within the year following the
      diagnosis. To date, the surgical resection remains the only treatment considered
      as curative. However, 80% of the patients are inoperable at the time of the
      diagnosis. Therefore, the intra-arterial injection (this tumour being
      hypervascularised) of antitumour agents is an interesting therapeutic option,
      more particularly the injection of Lipiodol coupled with iodine 131. The present
      paper describes the conditions when the interstitial curietherapy appears to be a
      valuable treatment to be considered.

PMID- 18069571
TI  - [Clinical case of the month. Computerized tomographic diagnosis of hematoma of
      the rectus abdominis muscle].
AB  - The development of an acute abdominal pain and of a palpable mass following a
      muscular strain, such as after coughing or sneezing, are features higly
      suggestive of an abdominal wall hematoma in the patient with predisposing
      factors. The diagnosis is often difficult since the condition mimics the clinical
      features of other abdominal pathologies. The diagnostic accuracy has
      significantly improved however after the advent of ultrasonogarphy and of
      computed tomography. Once the diagnosis is confirmed, the patient should be
      treated conservatively since surgery entails the risk of various complications.

PMID- 18069572
TI  - [Aspirin resistance in diabetic patients: laboratory entity or clinical
      reality?].
AB  - Aspirin is considered the gold standard antiplatelet therapy for primary and
      secondary prevention of cardiovascular (CV) disease. However, it appears less
      protective in diabetic patients than in the general population. This difference
      is attributed to a higher level of aspirin resistance observed in these subjects
      when in vitro tests are performed. The frequency of this problem, its mechanistic
      aspects and its clinical relevance remain largely unknown. Our analysis of the
      literature confirms a higher proportion of platelets resistant to aspirin in
      diabetic than in control individuals. This observation deserves further research
      because it may be associated with an increased risk of CV events and worse
      prognosis.

PMID- 18069573
TI  - [To give birth: in the past and today].
AB  - Nowadays in industrialized regions, the majority of childbirths take place in a
      hospital under high medical and paramedical supervision; this renders the rate of
      perinatal events very low. This obstetrical safety progressively developped
      through a practice that, at times, was studded with strange recommendations as
      well as ingenious concepts. The progress of Medicine and the emancipation of
      Woman deeply modified the approach to child delivery and influence the importance
      of its different actors. The current tendency towards a "more natural delivery"
      may be stepping away from the security of childbirth in a hospital setting.

PMID- 18069574
TI  - [Discontinuation syndrome associated with antidepressants].
AB  - Sometimes, the discontinuation of antidepressant therapy is associated with both
      physical and psychological symptoms. These symptoms are parts of the
      discontinuation syndrome and are very different from relapse or recurrence. The
      discontinuation syndrome appears within 1 week and lasts about 3 weeks after
      discontinuation of the antidepressant. In the vast majority of cases, the
      symptomatology is self-limiting. Sometimes, in the presence of a severe syndrome,
      reintroduction of the antidepressant induces a rapid resolution of the symptoms.
      In fact, the discontinuation of the antidepressant should be progressive.

PMID- 18069575
TI  - [Oxidative stress].
AB  - Oxidative stress is defined as an imbalance between the production of reactive
      oxygen species (ROS) and the antioxidant network, in favour of the former. Our
      lifestyle (smoking, alcoholism, obesity, intense physical exercise), but also our
      inadequate diet, contributes to significantly increase the production of ROS in
      our organism. This is potentially associated with an increased risk of developing
      ageing-related pathologies such as cardiovascular diseases and cancer. As a
      matter of prevention, it is necessary to have in hands a high technology allowing
      to correctly evidence the oxidative stress status of an individual in order to
      render optimal our antioxidant defences and to decrease the oxidative damages in
      DNA, proteins and lipids.

PMID- 18069576
TI  - [Clinical trial of the month. ADVANCE: improved survival and better vascular and
      renal outcomes with a fixed combination of perindopril and indapamide in patients
      with type 2 diabetes].
AB  - The controlled ADVANCE trial compared the incidence of major macrovascular and
      microvascular complications in 5,569 type 2 diabetic patients randomised to a
      fixed combination of perindopril and indapamide and in 5,571 patients randomised
      to placebo, followed for a mean duration of 4.3 years. Compared with patients
      assigned placebo, those assigned active therapy had a mean reduction in systolic
      blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg, despite
      the fact physicians were allowed to adjust antihypertensive therapy ad libitum.
      The relative risk of a major macrovascular and microvascular event (primary
      endpoint) was reduced by 9% (p = 0.041) in the active group. The separate
      reductions in macrovascular and microvascular events were similar but were not
      independently statistically significant. The relative risk of death was
      significantly reduced by 14% (p = 0.025), essentially due to a lower death rate
      from cardiovascular diseases (-18%; p = 0.027). The incidence of any coronary
      event was also significantly reduced (-14 %; p = 0.020), while only a trend was
      observed for all cerebrovascular events. Finally, renal events were significantly
      less frequent (-21%; p < 0.0001) whereas all ocular events were only slightly
      reduced (-5%; NS) in the active group as compared to the placebo group. The fixed
      combination of perindopril and indapamide was well tolerated and easy to
      administer. Overall one death due to any cause would be averted among every 79
      diabetic patients assigned active therapy for 5 years. There was no evidence that
      the effects of the study treatment differed by initial blood pressure level or
      concomitant use of other treatments at baseline.

PMID- 18069577
TI  - D. J. du Plessis Lecture. The value of research in surgery. Presented at the 34th
      meeting of the Surgical Research Society of Southern Africa, University of
      Kwazulu-Natal Medical School, Durban, 7 July 2006.

PMID- 18069578
TI  - Ischaemic preconditioning of the liver before transplantation.
AB  - PURPOSE: Assessment of the effect of a short ischaemic time prior to liver
      transplantation on the liver graft. METHODS: White X Landrace pigs (N=10) were
      subjected to liver transplantation. Before being removed from the donor animal,
      the livers were randomised into two groups: group 1--pre-procurement ischaemia
      (15 minutes' temporary arrest of portal venous and hepatic arterial inflow to the
      liver, followed by reperfusion of these vessels for a period of 15 minutes);
      group 2--no prior inflow occlusion (control group). In group 1 a spleno-jugular
      bypass was established to prevent venous congestion, portal venous hypertension,
      intestinal oedema and bacterial translocation. The livers were perfused with
      Eurocollins solution (4 degrees C), after which they were stored on ice for a
      period of 3 hours' cold ischaemic time. Hepatocellular injury was assessed
      according to liver cell function tests (aspartate aminotransferase, AST),
      biochemical indicators of reperfusion injury (malondialdehyde) and
      histopathology. RESULTS: There was a significant rise of AST in both groups 1
      hour after transplantation (from 51 +/- 27 IU/l to 357 +/- 152 IU/l in group 1
      and from 29 +/- 10 IU/l to 359 +/- 198 IU/l in group 2). AST levels were
      marginally lower in group 1 at 2 and 4 hours after transplantation. There was
      also a rise in malondialdehyde levels in both groups at 5, 20, 40 and 60 minutes
      after transplantation. Levels of malondialdehyde were lower in the primed group
      at 5, 20 and 40 minutes, while the levels at 60 minutes after transplantation
      were comparable. Histological changes, as measured by vacuolisation, neutrophil
      infiltration and hepatic cell necrosis, were less in livers transplanted after
      ischaemic preconditioning, although the difference was not significant.
      CONCLUSIONS: Ischaemic preconditioning of the donor liver seems to decrease
      hepatocellular damage, reperfusion injury and histological changes in the liver
      after transplantation. Further studies with larger numbers are indicated.

PMID- 18069579
TI  - Non-operative management of abdominal stab wounds--an analysis of 186 patients.
AB  - BACKGROUND: The modern management of abdominal stab wounds remains controversial
      and subject to continued reappraisal. In the present study we reviewed patients
      with abdominal stab wounds to examine and validate a policy of selective non
      operative management with serial physical abdominal examination in a busy urban
      trauma centre with a high incidence of penetrating trauma. METHODS: Over a 12
      month period (2005), the records of all patients with abdominal stab wounds were
      reviewed. Patients with abdominal stab wounds presenting with peritonitis,
      haemodynamic instability, organ evisceration and high spinal cord injury
      underwent emergency laparotomy. No local wound exploration, diagnostic peritoneal
      lavage or ultrasound was used. Haematuria in patients without an indication for
      emergency surgery was investigated with a contrasted computed tomography (CT)
      scan. Patients selected for non-operative management were admitted for serial
      clinical abdominal examination for 24 hours. Patients in whom abdominal findings
      were negative were given a test feed. If food was tolerated, they were discharged
      with an abdominal injury form. RESULTS: One hundred and eighty-six patients with
      abdominal stab wounds were admitted. There were 171 (91.9%) males, with a mean
      age of 29.5 years. Seventy-four patients (39.8%) underwent emergency laparotomy.
      There were 5 negative laparotomies (6.8%). The remaining 112 patients (60.2%)
      were assigned for abdominal observation. One hundred (89.3%) of these patients
      were successfully managed non-operatively. The remaining 12 patients underwent
      delayed laparotomy, which was negative in 2 cases (16.7%). Non-operative
      management was successful in 53.8% of patients overall. The overall sensitivity
      and specificity of serial abdominal examination was 87.3% and 93.5%,
      respectively. CONCLUSION: Serial physical examination alone for asymptomatic or
      mildly symptomatic patients with abdominal stab wounds enables a significant
      reduction in unnecessary laparotomies.

PMID- 18069580
TI  - The incidence of malignancy in neoplasms of the submandibular salivary gland.
AB  - OBJECTIVE: To test the validity of the reported high incidence (50%) of
      malignancy in neoplasms of the submandibular salivary gland, and to compare it
      with that of the parotid gland. METHODS: This is a retrospective analysis of
      major salivary gland neoplasms in 127 patients who were treated between August
      1988 and December 2004 (15 1/2 years) at Kalafong Hospital, Pretoria. RESULTS:
      All but 1 of the patients were black. There were 100 benign and 27 malignant
      tumours. Thirty tumours were in the submandibular gland, including 3 malignant
      tumours, i.e. 10%. Of 97 parotid gland tumours, 24 (24.7%) were malignant.
      CONCLUSION: The 10% incidence of malignancy in neoplasms of the submandibular
      gland in our series is much lower than the 50% reported in the literature. We
      postulate that race (black ethnicity) is probably a factor in this low incidence.

PMID- 18069581
TI  - Lymphoepithelial lesions of the parotid gland in the HIV era--a South African
      experience.
AB  - OBJECTIVE: Historically, lymphoepithelial lesions (LELs) have been a peripheral
      indication for surgery on the parotid gland, accounting for less than 1% of all
      parotidectomies undertaken. In the HIV era the profile of parotidectomy has
      changed, with LEL becoming a common indication for parotidectomy, prompting a
      review of our current experience. DESIGN: A retrospective study was undertaken
      between January 1998 and December 2005. Setting. Surgical services at King Edward
      VIII Hospital, Durban. SUBJECTS: All patients presenting with parotidomegaly.
      RESULTS: One hundred and sixty-two patients with parotidomegaly were evaluated;
      53 (32.7%) had LEL lesions. A total of 151 parotidectomies (including 42
      parotidectomies undertaken for LEL lesions) were performed in 147 patients.
      Radiotherapy was offered to 11 patients with LEL lesions. Complications following
      parotidectomy for LEL included facial nerve palsy (N=3), seroma formation (N=5)
      and facial artery false aneurysm (N=1). Three patients required re-parotidectomy
      for recurrent LEL parotidomegaly. In the patients who underwent radiotherapy,
      there was a satisfactory outcome; 2 patients who received 4 Gy radiation per
      sitting developed mild skin discolouration of the treated area. CONCLUSION:
      Although surgical management of LEL parotidomegaly may provide a satisfactory
      result, this approach is technically challenging and is associated with
      complications and recurrences. For these reasons, the non-operative approach
      employing radiotherapy should be considered.

PMID- 18069582
TI  - Meningococcal septicaemia complications involving skin and underlying deeper
      tissues--management considerations and outcome.
AB  - OBJECTIVE: To describe surgical experience with purpura fulminans related to
      meningococcaemia in a single institution, and to suggest a management protocol.
      METHODS: A retrospective review was done of patients admitted to the intensive
      care unit at Red Cross War Memorial Children's Hospital in Cape Town with the
      clinical diagnosis of purpura fulminans. RESULTS: During a 28-year period (1977
      2005) 112 children (average age 3.4 years) were treated for meningococcaemia with
      purpura fulminans. Overall mortality was 10.7%. Local treatment consisted of
      measures to improve circulation, infection control and healing of necrotic
      tissue. Demarcation of necrotic areas was evident at 5.5 days and the average
      area of skin necrosis was 14% total body surface area (range 2-85%). The lower
      limbs were predominantly affected. Purpura fulminans resolved in 35 children
      (31.2%) without skin necrosis. Skin grafting was required in 77 children (68.8%).
      Factors associated with a poor outcome for peripheral extremity salvage were
      progressive irreversible skin changes, early disappearance of distal pulses,
      tense cold swollen extremities and intense pain on passive movement of the
      affected extremity. Amputations were performed proximal to the area of necrosis,
      on average 27 days after injury. CONCLUSIONS: Meningococcaemia is a disease with
      potentially devastating consequences. Early surgical consultation is essential.
      Skin- and soft-tissue-releasing incisions should be considered early to reduce
      the incidence of extremity necrosis. Small necrotic areas usually separate
      spontaneously with secondary healing or can be excised and sutured. Larger
      necrotic areas should be excised only after demarcation has been established, and
      can be covered with delayed skin grafting. Amputation should be conservative but
      may require revision.

PMID- 18069583
TI  - Adenocarcinoma in a retrorectal cystic hamartoma: a case report and literature
      review.
AB  - Retrorectal cystic hamartomas are rare congenital lesions derived from the
      vestigial portion of the embryonic hindgut. These lesions present in a vague
      manner and so mimic the presentation of more common mass lesions in the pelvic
      region. They most frequently afflict middle-aged women, causing vague pelvic
      pains, discomfort with defaecation or sitting, and altered bowel function.
      Malignant transformation within these lesions is extremely rare. We describe a
      case of adenocarcinoma within a retrorectal cystic hamartoma, initially
      manifesting in a 54-year-old woman and recurring over a'5-year period. A computed
      tomography (CT) scan and pathology reports are included in the study, and
      findings at operations are discussed. We also include a comprehensive review of
      the literature.

PMID- 18069584
TI  - Magnetic foreign body on the nasal septum.
AB  - A 9-year-old boy presented to our department 8 days after attempting to insert a
      non-piercing magnetic ear stud on either side of his nose. He had been unable to
      remove them, and both magnetic parts of the ear studs were still present in his
      nose. Examination of the nose was difficult, as he was unco-operative and his
      nose was filled with mucus and crusts. X-rays of the nose revealed the two ear
      studs on either side of the nasal septum (Fig. 1). The magnets had caused
      compression and thinning of the septal cartilage. Examination under general
      anaesthesia revealed the two magnets embedded into the mucosa across the septum.
      The magnets were removed under general anaesthesia by clamping and sliding them
      in opposite directions. The exposed compressed cartilage was gradually covered by
      granulation tissue and eventually nasal mucosa.

PMID- 18069586
TI  - Life insurance solutions for unmarried couples.

PMID- 18069585
TI  - Parotidectomy in southern Africa.

PMID- 18069587
TI  - Understanding hird requirements.

PMID- 18069588
TI  - Complacency about dental services for Massachusetts residents with disabilities.

PMID- 18069589
TI  - Is human bone allograft safe for the management of alveolar defects? A primer for
      patient consent.
AB  - Allograft bone has been used safely and extensively in dental and implant surgery
      for more than 35 years, and increased federal regulation only serves to enhance
      an exceptional safety record. However, proper selection of tissue from accredited
      banks by a knowledgeable clinician, and compliance with tracking and
      recordkeeping recommendations, will provide the ultimate benefit to the patients
      who trust our clinical judgment for their wellbeing.

PMID- 18069590
TI  - Computer-guided Implant dentistry.
AB  - Computer-guided minimally invasive implant treatment promises to revolutionize
      the way we practice implant dentistry. This new technology allows implants and
      associated restorations to be precisely placed at the same procedure directly
      through the gingiva in an hour or less. Since there is no incision, there is
      minimal postoperative discomfort or swelling and no sutures.

PMID- 18069591
TI  - Immediate implant therapy in clinical practice: single-tooth replacement.
AB  - Once viewed as an esoteric treatment option, implant therapy has demonstrated
      long-term predictability at least equal to that of more "conventional" treatment
      modalities. The continued evolution of implant surface technology and restorative
      options has made implant therapy the treatment modality of choice in many if not
      most, clinical situations. It is, therefore, only natural that the role of
      immediate implant therapy continues to expand. Proponents of immediate implant
      therapy advocate its use at the time of tooth removal or, in a partially or fully
      edentulous arch, to meet a variety of clinical challenges.

PMID- 18069592
TI  - The 2007 American Heart Association guideline for the prescription of antibiotic
      prophylaxis: a brief overview.

PMID- 18069593
TI  - A clinico-pathologic correlation. Cherubism.

PMID- 18069594
TI  - Cinnamon stomatitis.

PMID- 18069595
TI  - What every dentist should know about the "z-sedatives".
AB  - According to the National Institutes of Health, approximately 30 percent of all
      Americans complain of sleep disruption, while 10 percent display symptoms
      congruent with chronic insomnia. One of the most common treatments for insomnia
      is prescription sleep medications that help people fall asleep and remain asleep.
      Historically barbiturates were initially popular for treating insomnia, but their
      long "hangover" effect made them easily replaced with the introduction of the
      benzodiazepines. Triazolam (Halcion), diazepam (Valium), and oxazepam (Serax)
      rapidly became the treatment of choice for insomnia. Recently a new class of
      nonbenzodiazepines---the "z-sedatives"--has overtaken the older benzodiazepines
      as the most commonly prescribed sleep medications. The three most popular z-drugs
      are zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). The Food and
      Drug Administration (FDA) also recently approved the production of zolpidem
      tartrate, a generic form of Ambien. Many dentists prescribe these medications for
      patients who have difficulty sleeping the night prior to an appointment or as a
      procedural sedative. With 43 million prescriptions for sleep medications filled
      in 2005, generating $2.7 billion for pharmaceutical companies, it is important
      that dentists be aware of these drugs' mechanism of action and potential drug
      interactions.

PMID- 18069596
TI  - Salvaging a failing implant.

PMID- 18069597
TI  - [Paratuberculose enteritis and Crohn's disease].
AB  - Paratuberculose enteritis is an infectious and contagious chronic disease of the
      rumiants. It is characterised by periodic diarrhoea and progressive emaciation
      and loss of condition, intestinal ileitis and oedematous mucosa with
      cirumvolutions. The disease is caused by Mycobacterium avium subsp.
      paratuberculosis. Crohn's disease or inflammatory bowel disease has identical
      characterization with ileitis, colitis with oedematous state and enlarged
      intestinal mucosa. Iflammatory infiltration of the intestinal mucosa has a
      transmural character, affecting the submucosa. The similarity between Crohn's
      disease and Johne's disease is the reason for considering an identical etiology
      for both diseases, but in the 75 years of the natural history of Crohn's disease
      it has been impossible to demonstrate this hypothesis. However, actually the
      predominant idea is that Mycobacterium avium subsp. paratuberculosis is
      frequently present in patients with Crohn's disease. This has been demonstrated
      by hemocultures, PCR and in situ hybridization.

PMID- 18069598
TI  - [New strategies in the treatment of atrial fibrillation].
AB  - Atrial fibrillation (AFb) is the most common sustained cardiac arrhythmia. Once
      initiated, AFb alters atrial electrical and structural properties (remodeling)
      that promotes its maintenance and recurrence. Treatment is directed to restore
      and maintain the sinus rhythm, to control the ventricular rate and to prevent
      thromboembolic complications. Recent evidence indicates that angiotensin
      converting enzyme inhibitors, angiotensin AT1 receptor antagonists and statins
      modify atrial remodeling and reduce the incidence of AFb, thus possibly
      representing a new alternative in the treatment of the arrhythmia.

PMID- 18069599
TI  - [Meningiomas: new prognostic factors].
AB  - Meningiomas are still defined as benignant tumours although 25% of those tumours
      will have local recurrance in the follow-up period. The WHO (2000) classification
      divides meningiomas in three goups: Grade 1 for conventional meningioma. Grade 2
      for atypical meningioma and Grade 3 for Anaplastic meningioma. Specific
      histological variants of meningiomas have been included in grade 2 tumours. Clear
      cell, rabdoid and papillary meningiomas. We obtained 250 meningiomas from our
      files and we analyzed 30 inmunohistochemical markers. Several markers can be
      actually used as prognostic indicators in meningiomas and may allow a more
      individualized management of patients.

PMID- 18069600
TI  - [William's syndrome].
AB  - William's syndrome is of great interest to neurosclence as it is expected to help
      understand the genetic and neural mechanisms that underlie our cognitive systems.
      Although patients with this syndrome have moderate levels of learning disability,
      some of them, however, have superior skills in language, auditory memory, face
      recognition, empathy with others and a passion for music. The theory that best
      explains this syndrome is that the degeneration of the functions of the left
      hemisphere generates a compensation via an increase in the functions of the right
      hemisphere.

PMID- 18069601
TI  - [The clinical challenge of the atrial fibrillation].
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical
      practice. It consists in the triggering of 300 to 600 atrial waves per minute.
      The ventricular rate depends of the AV node refractory period that without
      treatment it is very high. This rapid response reduces the ventricular filling
      period with two consequences, the increase of venous pressures, and the reduction
      of the cardiac output, determining heart failure and myocardial ischaemia. The
      lack of atrial contraction, induces thrombus formation with high risk for
      systemic embolism. Cardioversion of atrial fibrillation is associated with an
      increased risk of stroke. Thromboembolism happens when atria recover the
      contraction, that in chronic AF can be several weeks after cardioversion. The
      management of AF involves three objectives: stroke prevention, rate control, and
      correction of rhythm disturbance. We need an appropriate approach to
      antithrombotic therapies for stroke prevention. A proper strategy and safe use of
      old and new Drugs for rate control or non electrical cardioversion to sinusal
      rhythm. The useful of statins, ARBII and ACEI for the primary and secondary
      prevention of AF. For symptomatic patients the electrical managing of the AF is
      the alternative. Cardioversion is performed as part of a rhythm-control treatment
      strategy but ablation of the perivenosos pulmonary circuits, ablation of the AV
      node and implantation of a pacemaker are another alternatives.

PMID- 18069602
TI  - [Spa treatment and health status].
AB  - Spa treatment, in its global complexity, is an active therapeutic way of
      treatment, capable to have an influence on the somatic and psychological status
      of the patient, seen its proven utility for protecting and restoring health. Spa
      treatment acts on the patient, in his body and mind, being a valuable complement
      of usual medical practices, at any age and circumstances. In spite of the short
      period of application (2 to 4 weeks), a considerable wellness is obtained when
      the indication and way of treatment are adequate, valuing the good results that
      can be reached in people of advanced age, depressive status and some other
      illnesses.

PMID- 18069603
TI  - [Modulation by the GABA of the ventro-oral-pontine reticular REM sleep-inducing
      neurons].
AB  - From a multidisciplinary study in our laboratory we have compiled numerous
      findings on the role played by the inhibitory neurotransmitter GABA in the
      ventral part of the oral pontine reticular nucleus (vRPO), REM sleep induction
      and maintenance brainstem structure. Functional GABA in the vRPO is located in a
      few small and scattered neuronal bodies, and in an abundant number of synaptic
      terminals: 30% of all synaptic terminals in vRPO are GABAergic. These terminals
      form inhibitory, symmetric synapses on the soma and different segments of the
      dendritic tree of the vRPO neurons, mainly in those of large diameter. In unitary
      intracellular studies, in vitro, we have demonstrated that GABA produces
      hyperpolarization of the vRPO neurons. In vivo experiments in freely moving cats,
      local microinjections of the GABA(A) receptor agonist muscimol decreased REM
      sleep. The different densities of GABA-immunoreactions and the diverse and
      complex morphological ultrastructure of the vRPO GABAergic terminals suggest that
      they have different origins and physiologic functions. There are GABAergic
      projections to the vRPO from diencephalic structures related with the other
      phases of the sleep-wakefulness cycle: wakefulness and non-REM sleep, which may
      be anatomical substrata for the GABAergic inhibition of the vRPO REM sleep
      inducing neurons during these other phases.

PMID- 18069604
TI  - [Medical teaching adapted to European higher education area].
AB  - The main aspects of the European Higher Education Area, its structure and the
      European Credit Transfer System are shown, as well as the last guidelines of the
      Spanish Ministry of Education about these matters. The knowledge and the skills
      the students of Meeicine must acquire according to the "White Book" of the
      Spanish National Deans Conference are shown, as well as the advances made by the
      School of Medicine of Complutense University on order to approach to the European
      Higher Education Area, specially those related to new teaching methods.

PMID- 18069605
TI  - [Sierra of the Atapuerca, thinking about the evolution].
AB  - Homo sapiens walks to the future in a uncertain way. The fosil evidences from the
      lithosphere can help us to get into know the social and cultural evolution of all
      the species that have precede us and even our own. Atapuerca, with more than 1.2
      MA old of fossilized history from the Pleistocene to the Holocene is throwing a
      scientific message through the study of all its archaeological sites. There are
      thousands of animal and human fossils in Trinchera del Ferrocarril, Cueva de Gran
      Dolina, Sima del Elefante and Galeria that yield information on the cultural
      cannibalism practices by Homo antecessor 900,000 years ago, and the hunting and
      gathering that Homo heidelbergensis developed 400,000 years ago. Finally in the
      Sima de los Huesos, with a similar chronology than at the H. heidelbergensis
      sites from the Trinchera del Ferrocarril, we find the first intentional
      accumulation of hominid bodies. These contributions are significant to the
      knowledge of the biological and cultural human evolution and permits to deepen it
      empirically. We hope that understanding the message we will be able to improve
      our species through the socialization of the scientific knowledge.

PMID- 18069606
TI  - [Leonardo Torres Quevedo: the most prodigious inventor of his time].
AB  - Leonardo Torres Quevedo's contribution to "the conquest of the air", to which
      humanity devoted so much effort in the early twentieth century is describe and
      his original inventions on dirigibles -the "Torres Quevedo", the "Astra-Torres"
      and the "Coastal"- and cable cars - Monte Ulia (San Sebastian) y Spanish Aerocar
      (Niagara, Canada) are emphasised.

PMID- 18069607
TI  - [The new preventive medicine].
AB  - The purpose of the Exams in Health is to describe the prepathogenetic illness.
      Important successes have been obtained in the prevention of many illnesses, as
      some congenital metabolic diseases, the tuberculosis, mamma cancer and uterus
      cancer, etc. It is possible to act in a stage previous of the Natural History,
      the predisposition. It is the current frontier of the Preventive Medicine whose
      characteristic are developed in the text.

PMID- 18069608
TI  - [The atopy enigmas and the present validity of the concept of heteroallergy].
AB  - The phenomena of altered reactivity refer to all pathological symptoms, neither
      toxic nor infectious, that a human or animal organism presents after contact with
      some organic substance, dead or alive, and which are due to a state of altered
      reaction based on an antigen-antibody mechanism. It was named "Allergy" by Von
      Pirquet. Within the field of allergy Coca and colleagues distinguished a special
      type which they called "Atopy" (1931). In the course of time the allergic
      character of the atopic processes such as bronchial asthma, hay fever and atopic
      dermatitis was doubteld, and nowadays it is thought that atopy is a
      "constitutional disreaction of the skin and/or mucos, frecuently associated with
      immunological anomalies which are hardly ever its cause". The term
      "Heteroallergy" used by Dujardin and Decombe (1925) refers to the Fact that a
      permanent state of latent allergy increases the general reactivity of the
      organism that may present pathological symptoms. Although forgotten in the
      medical literature the concept is still alive and it has been mentioned
      subsecuently by several authors such as Jimenez Diaz (1932), Strauss and Kligman
      (1957) and Heilmeyer (1962).

PMID- 18069609
TI  - [About a new medical primary language].
AB  - The author, Medical Doctor from half a century, because his interest in Art, has
      studied Art Philosophy and History at the Madrid University. He found among the
      primary civilizations many pictures and sculptures with illness showed as Art,
      but not included in the books of History of Medicine. In this paper he shows a
      palimpsest to demonstrate that the four Mesoamerican cultures, before the arrival
      of Spaniard, without cultural or artistic influences, pictured a lot of
      congenital malformations and illness. The author exposes his original point of
      view to explain these findings.

PMID- 18069610
TI  - [Estrogens: friends or foes?].
AB  - After carrying out several clinical randomized trials at the end of the 90
      ties,positive effects of the treatment with estrogens on the cardiovascular
      system were not confirmed in the woman. The negative effect on mammary cancer was
      confirmed. In this paper results have been critically analized and data are
      presented, which confirm the beneficial effects of estrogens at vascular, bone,
      skin and immune systems.

PMID- 18069611
TI  - [Tissue engineering of the oral mucosa].
AB  - We report our experience in developing a mechanism to build a full-thickness oral
      mucosa substitute using cell culture and protocols of tissue engineering. We
      generated primary cultures of human oral mucosa fibroblasts and keratinocytes
      from small biopsies of normal oral mucosa using enzymatic treatments. Each type
      of cell was cultured in selective medium. Microanalytical quality control of cell
      viability was carried out. A multilayered oral mucosa construct was built by
      sequential deposition of fibroblasts immersed a gel of human fibrin and
      epithelium in a manner that reproduce the normal histological structure.
      Histological and genetic quality control studies suggest that our model show
      similarities with native human oral mucosa.

PMID- 18069612
TI  - [Targeted therapy for cancer: anti-tyrosine kinase receptor agents].
AB  - The use of drugs to treat cancer based on molecular targets is common fact,
      especially those targeting kinases that are involved in the cellular signalling
      pathways. The anti-tyrosine receptor drugs are among the most developed, some of
      them having already been approved by the FDA and the EMEA for breast cancer,
      colorectal, lung GIST and renal cancer treatment. Although these drugs are
      currently focused on a single target, the future challenge is to hit several
      targets simultaneously, along with combined chemotherapy. Thus we are facing the
      beginning of a new era in the battle against cancer.

PMID- 18069613
TI  - [Nanotechnology, nanomedicine and nanopharmacology].
AB  - Based on Nanotechnology methods, Nanomedicine and Nanotecnology will obtain
      significant advances in areas such as Diagnostic, Regenerative Medicine and
      pharmacological Therapeutics. With nanotechnology-based drug delivery
      systems,important improvement on pharmacokinetics of drugs will take place, due
      to increased solubility, protection against decrease in drug effects due to
      excessive metabolism and subsequent increase of bioavailability. Improvement on
      pharmacodynamic parameters will occur also due to increased drug concentration in
      target tissues. Also the use of Nanotechnology in the modern pharmacology will
      serve for a more accurate control of doses, which will decrease significantly
      drug toxicity.

PMID- 18069614
TI  - [Social medicine's actuality: epidemiology sanitary's foundation].
AB  - Appear the Spanish official data of mortality and morbility, as well as available
      of obesity and the metabolic syndrome to base the thesis of which the pathogenic
      style of life is the main determinant of one and others. Considerations become on
      their meaning epidemiologist as well as the forced repercussions in the decisions
      on the sanitary policy, that must take care of the social causes of becoming ill
      than their individual consequences more, in a etiologic perspective than more
      anatomoclinic.

PMID- 18069615
TI  - Bacterial protein meal in diets for pigs and minks: comparative studies on
      protein turnover rate and urinary excretion of purine base derivatives.
AB  - The effect of increasing the dietary content of bacterial protein meal (BPM) on
      protein turnover rate, and on nucleic acid and creatinine metabolism in growing
      minks and pigs was investigated in two experiments. In each experiment, 16
      animals were allocated to four experimental diets. The diets containing no BPM
      served as controls, i.e. for minks diet M1, for pigs P1; the experimental diets
      contained increasing levels of BPM to replace fish meal (minks) or soybean meal
      (pigs), so that up to 17% (P2), 20% (M2), 35% (P3), 40% (M3), 52% (P4), and 60%
      (M4) of digestible N was BPM derived. Protein turnover rate was measured by means
      of the end-product method using [15N]glycine as tracer and urinary nitrogen as
      end-product. In minks, protein flux, synthesis, and breakdown increased
      significantly with increasing dietary BPM. In pigs, diet had no observed effect
      on protein turnover rate. The intake of nucleic acid nitrogen (NAN) increased
      from 0.15 g/kg W0.75 on M1 to 0.26 g/kg W0.75 on M3 and M4 in the mink
      experiment, and from 0.08 g/kg W0.75 on P1 to 0.33 g/kg W0.75 on P4 in the pig
      experiment. Increased NAN intake led, in both experiments, to increased allantoin
      excretion. Analysis of species effects showed that minks excreted 1.72 mmol/ kg
      W0.75 of allantoin, significantly more than the 0.95 mmol/kg W0.75 excreted by
      pigs. In minks, approximately 96% of the excreted purine base derivatives
      consisted of allantoin, whereas in pigs approximately 93% did. Thus, increasing
      the dietary content of BPM increased protein turnover rate in minks but not in
      pigs, and allantoin excretion increased with increasing dietary BPM although it
      seemed that mink decomposed purine bases to their end-product more completely
      than pigs did. Collectively these data show that BPM is a suitable protein source
      for pigs and mink, and recorded differences between species were to a large
      extent due to differences in protein retention capacity and muscle mass.

PMID- 18069616
TI  - Influence of hydrocolloidal silver nanoparticles on gastrointestinal microflora
      and morphology of enterocytes of quails.
AB  - The objective of the present study was to examine the effects of hydrocolloidal
      silver nanoparticles (Ag-nano) on microbial profile of caecum and morphology of
      enterocytes in duodenum of Japanese quail, as a model animal for poultry. Quails
      (Coturnix coturnix japonica) (10 d old) were randomly divided into four groups
      (15 quails each) and located into four cages for 12 days. Quails were fed with
      granulated diets given ad libitum and had free access to drinking water. Ag-nano
      were added to drinking water at concentrations of 0, 5, 15 and 25 mg/kg. At the
      end of the experiment, the animals were killed and samples of duodenum and caeca
      microflora were collected. This initial investigation demonstrated that silver
      nanoparticles did not influence emphatically microflora of quail caecum; however,
      water containing 25 mg/kg of Ag-nano significantly increased the population of
      lactic acid bacteria. Furthermore, Ag-nano did not show any damaging properties
      on enterocytes of duodenal villi.

PMID- 18069617
TI  - Effects of dietary energy intake during gestation and lactation on milk yield and
      composition of first, second and fourth parity sows.
AB  - In order to determine the effects of a varied level of dietary energy intake
      during pregnancy and lactation on milk yield and composition, first, second and
      fourth parity sows (Large White x German Landrace) were provided with energy at a
      level of either: (i) 100% of ME requirement (MEreq) during pregnancy and
      lactation, (ii) 120% MEreq during pregnancy and 80% during lactation, and (iii)
      80% MEreq during pregnancy and 120% during lactation. In spite of equal target
      levels feed analysis revealed that gestating first parity sows with 120/80
      treatment combination and lactating sows of 80/120 treatment combination received
      25, and 11-17% more digestible N than in the respective 100/100 treatment
      combination. Irrespective of this 120/80 sows responded with the highest milk DM,
      fat, and energy contents, and the lowest lactose concentrations whereas protein
      levels where not affected, irrespective of parity (p < 0.05). Milk yield of sows
      in 1st and 4th lactation was 85 and 106% of that in 2nd lactation, respectively.
      Average milk composition was 18.1% DM, 4.9% protein, 6.8% fat, 5.6% lactose, and
      0.8% ash. Milk composition changes ceased at day 7 of lactation with a reduction
      of milk GE and protein, and an increase of lactose content. Concentrations of
      threonine, arginine, valine, leucine, tyrosine, phenylalanine, cystine, and
      tryptophan, as well as stearic, oleic, and linoleic acid were higher in colostrum
      than in milk at later lactation stages. In contrast, laurine, myristic, palmitic,
      and palmitoleic acids were lower concentrated in colostrum. In conclusion, these
      results illustrate the importance of body reserve mobilization for milk
      production in sows and indicate that low energy supply during gestation cannot be
      compensated by higher energy supply during lactation.

PMID- 18069618
TI  - Piglet growth before and after weaning in relation to a qualitative estimate of
      solid (creep) feed intake during lactation: a pilot study.
AB  - The experimental objectives were to verify whether a qualitative measure of creep
      feed consumption using a dye was related to performance, and associate this with
      teat order. Indigo carmine (5 g/kg) was added to a starter diet between days 12
      and 31 (weaning) of lactation. On days 19, 23, 27 and 31, faeces from each piglet
      were assessed for colouration. Each piglet was categorized as a 'good',
      'moderate' or 'small/non' eater of feed. There were no differences in pre-weaning
      growth rate between categories. Piglets classed as 'good' or 'moderate' eaters in
      lactation grew fastest (p = 0.009) in the first three days after weaning, but
      between days 4 and 7, the highest growth rate occurred in 'moderate' eaters.
      'Small/ non' eaters grew slower (p < 0.01) between weaning and 28 days after
      weaning. Piglets drinking milk from anterior teats were heavier at weaning (p <
      0.001) and for the first 14 days after weaning (p = 0.104) compared to piglets
      sucking posterior teats. Data from this study demonstrated that creep feed intake
      of piglets could qualitatively be assessed using indigo carmine, and that this
      categorization was related to performance in the immediate post-weaning period.

PMID- 18069619
TI  - Palatability in sheep and in vitro nutritional value of dried and ensiled
      sainfoin (Onobrychis viciifolia) birdsfoot trefoil (Lotus corniculatus), and
      chicory (Cichorium intybus).
AB  - Three temperate forages, sainfoin, birdsfoot trefoil, and chicory, characterized
      by elevated contents of plant secondary compounds, were compared to a ryegrass
      clover mixture (control) in dried (Experiment 1) and ensiled form (Experiment 2)
      in their palatability and nutritional value. Palatability was measured in adult
      wethers (n = 6) allowed to choose between the familiar control forage and one of
      the three test plants. Palatability index was calculated from differences in
      intake of control and test plants measured after given times. Generally at first
      contact, palatability of the unfamiliar plants was low. Lag time until
      palatability index approached or exceeded a value of 100 was 2-5 d, but could not
      be related to the content of condensed tannins. Sainfoin had a high palatability,
      the highest content of condensed tannins (77.4 +/- 10.23 g/kg DM), a high content
      of duodenally utilisable crude protein (94.7 +/- 16.87 g/100 g CP), and a high
      content of metabolizable energy (9.5 +/- 0.38 MJ ME/kg DM), making this plant
      most promising for various purposes including anthelmintic action.

PMID- 18069620
TI  - Home and hospital; hospice and palliative care: how the environment impacts the
      social work role.
AB  - Social workers play key roles on interdisciplinary hospice teams and in hospitals
      on oncology or palliative care teams. Though palliative care settings include
      both home hospice and hospital-based consultation services, the different
      environments and scope of practice impact the role of the social worker. The
      purpose of this article is to examine the similarities and differences in
      coordination of care, teamwork, and collaboration in these two fields in order to
      highlight opportunities for enhancing clinical skills and developing our
      confidence and presence in asserting social work expertise with our
      transdisciplinary colleagues.

PMID- 18069621
TI  - Hospice use by older adults knocking on the door of the nursing facility:
      implications for social work practice.
AB  - Since 1983, federal funding has been available for hospice services. However,
      research studies have found that hospice is underutilized by people with terminal
      illnesses and their families. Low-income older adults are particularly at risk
      for underutilization. This study examined utilization of hospice services by
      nursing home applicants in one Midwestern state. Characteristics of users and non
      users, and potential barriers to hospice use were examined. Findings further
      document that hospice is underutilized, especially by the Medicaid population,
      and point to barriers to hospice utilization. Specific recommendations are made
      to help practitioners increase hospice access.

PMID- 18069622
TI  - Advance care planning throughout the end-of-life: focusing the lens for social
      work practice.
AB  - Advance care planning throughout the end-of-life is an increasingly important
      aspect of professional practice with older adults and their families. As the
      nation's population continues to live longer, more and more people will
      experience years of functional and cognitive decline prior to death. This article
      discusses the growing importance of advance care planning using a long-range,
      holistic perspective of examining care needs throughout the end of life. End-of
      life care is conceptualized by three trajectories of decline leading to death,
      with about two-thirds of all older adults succumbing to four key conditions:
      congestive heart failure, emphysema, frailty, and dementia. Research regarding
      the advance care planning needs of older adults with the key conditions is
      presented. Further research is needed to enhance social work practice in this
      area.

PMID- 18069623
TI  - Long-term planning and decision-making among midlife and older gay men and
      lesbians.
AB  - This article examines the issues of long-term planning and decision-making among
      midlife and older gay men and lesbian caregivers. Using a qualitative
      methodology, in-depth interviews were conducted with 19 gay men and lesbians over
      50. Participants reported on their long-term planning and decision-making
      processes. All but four persons reported that their partners had advance
      directives, but the majority of caregivers did not have advance directives for
      themselves. Concerns about informal family dynamics and interactions with formal
      systems were expressed, along with financial and ownership issues. It is
      important for social workers to intervene across individual, organizational, and
      community levels in advocacy for the needs of older gay men and lesbian clients.

PMID- 18069624
TI  - [The state of the art in 4-dimensional radiotherapy].

PMID- 18069625
TI  - [CDK1 expression and effects of CDK1 silencing on the malignant phenotype of
      glioma cells].
AB  - OBJECTIVE: Our previous cDNA array data have shown that expression level of CDK1
      increased along with the malignant progression of ganglioglioma, and decreased
      with the differentiation process of neural stem cells. The purpose of this study
      was to investigate the CDK1 expression levels in gliomas and the effects of CDK1
      knockdown on phenotype of glioma cells. METHODS: Glioma tissue array was
      constructed, which was composed of surgical specimens of gliomas with different
      malignancy grades, glioma xenografts in nude mice, cellular spheroids of brain
      tumor stem cells, normal neural stem cells and glioma cell line. CDK1 expression
      was detected in glioma tissue array with immunohistochemical techniques. CDK1
      expression in human brain glioma cell line and relevant xenogeneic graft tumor
      was inhibited by retroviral vectors expressing short hairpin RNAs (shRNAs). Both
      in vitro and in vivo changes of biological characteristics were further observed.
      RESULTS: The expression level of CDK1 increased along with the malignancy
      progression of glioma in clinical specimens. The positive expression rates of
      CDK1 in human brain glioma tissues were 22.2% (grade I), 40.0% (grade II), 69.6%
      (grade III) and 78.6% (grade IV), P = 0.01, respectively. The positive expression
      rate of CDK1 in glioma cell line and implanted xenografts was similar as the
      clinical tumors with high malignancy, and higher than those in neural stem cells
      and brain tumor stem cells (P = 0.0014). Expression of CDK1 was high in human
      fetal brain tissues and bone marrows of nude mice, but low in normal adult human
      brain tissues. Downregulation of CDK1 inhibited the proliferation activities
      notably both in SHG-44 cells in vitro and relevant xenogeneic graft tumors, and
      induced apoptosis of tumor cells prominantly as well. CONCLUSION: Overexpression
      of CDK1 may promote oncogenesis and progression of human gliomas. Downregulation
      of CDK1 expression can inhibit the proliferation activities of human malignant
      gliomas.

PMID- 18069626
TI  - [Establishment of RNA interfering retrovirus vector targeting CXCR4 gene driven
      by human prostate-specific antigen promoter and its biological effects on
      prostate cancer cells].
AB  - OBJECTIVE: To construct RNA interfering retrovirus vector targeting CXCR4 gene
      driven by human prostate-specific antigen promoter and investigate its targeted
      inhibition effects in androgen-responsive prostate cancer cells LNCaP. METHODS:
      To clone the CXCR4 targeting siRNA gene by PCR. The PCR products were inserted
      into the pGensil-1 plasmid containing U6 promoter and EGFP. U6 promoter was
      replaced by hPSA promoter. Then, the recombinant EGFP-hPSA-siCXCR4 fragment was
      sub-cloned into pLXSN, which was evaluated by restriction enzyme. The pLXSN-EGFP
      hPSA-siCXCR4 was transfected into PA317 cells with Lipofectamine 2000. The virus
      obtained from transfected PA317 cells was transfected into PC-3m, LNCaP and MCF-7
      cells, respectively. The expression of CXCR4 mRNA and protein was detected by RT
      PCR and Western blot. The invasion ability of prostate carcinoma cells was
      detected by Transwell experiment. RESULTS: The recombinant pLXSN-hPSA-siCXCR4 was
      successfully constructed. The expression of CXCR4 mRNA and protein in LNCaP cells
      was blocked by pLXSN-hPSA-siCXCR4. The expression inhibition rate was (81.53 +/-
      10.22)% at mRNA level detected by semi-quantitive RT-PCR and (90.52 +/- 9.31)% at
      protein level detected by Western blot, respectively, in LNCaP cells at 48 h. The
      expression of CXCR4 mRNA and protein was effectively inhibited by sequence
      specific hPSA-siCXCR4 in LNCaP cells, but not in PC-3m and MCF-7 cells. The
      results of Transwell experiment showed that the number of cells in down-pore of
      micro-membrane was 139.9 +/- 14. 2 in the treated group, significantly less in
      comparison with 348.4 +/- 36. 4 in the controlled group (P < 0.05). However, the
      number of PC-3m and MCF-7 cells in down-pore of micro-membrane was not
      significantly different among the control and treated groups (P > 0.05).
      CONCLUSION: The downstream siRNA controlled by hPSA promoter in retrovirus system
      can be expressed selectively in androgen-responsive prostate carcinoma cells,
      showing an apparent targeting character. RNAi targeted to CXCR4 driven by hPSA
      promoter has a potential value in gene therapy of androgen-responsive prostate
      cancer.

PMID- 18069627
TI  - [Effect and mechanism of apigenin on VEGF expression in human breast cancer
      cells].
AB  - OBJECTIVE: To study the effects and mechanism of apigenin on the expression of
      vascular endothelial growth factor (VEGF) in human breast cancer MDA-MB-231
      cells. METHODS: MDA-MB-231 cells were used as the study object. MTT assay was
      used to detect the effect of apigenin on the cell viability. ELISA was used to
      determine the protein level of VEGF. RT-PCR was used to detect VEGF at mRNA
      level. A double luciferase system was used to measure the transcription activity
      of VEGF. pCEP4-HIF-1alpha was transferred to explore the reversing effect of HIF
      1alpha on the inhibitory effect of apigenin on the transcription activity of
      VEGF. Western blotting was used to detect the time-dependent and dose-dependent
      effect of apigenin on HIF-lalpha, p-AKT, p-ERK, and p53 expression at protein
      level. RESULTS: Apigenin had no visible inhibitory effect on cell viability.
      Apigenin reduced the secretion of VEGF, mRNA levels of VEGF and transcription
      activity of VEGF. Furthermore, the inhibitory effect of apigenin on the
      transcription activity of VEGF could be reversed by transferring pCEP4-HIF-1alpha
      into the cells. Additionally, apigenin inhibited the expression of HIF-1alpha and
      p-AKT, induced the expression of p53, but had no effect on the expression of p
      ERK1/2. CONCLUSION: Apigenin can inhibit VEGF expression in breast cancer cells,
      and this effect may be achieved through decreasing the expression of HIF-1alpha.

PMID- 18069628
TI  - [Effects of endostatin and doxycycline on microcirculation patterns in melanoma
      and their relevant molecular mechanisms].
AB  - OBJECTIVE: To investigate the effects of endostatin and doxycycline on
      microcirculation patterns in melanoma and their molecular mechanisms. METHODS: To
      establish mouse B16 melanoma model by subcutaneous injection of B16 melanoma cell
      suspension. The mice were divided into 3 experimental groups and 1 control group.
      To treat the mice in the 3 experimental groups with endostatin, doxycycline,
      endostatin and doxycycline, respectively, and the control group without any
      treatment. The tumor volume was measured and recorded to make comparison of their
      growth rate. To assess the expression of MMP-2, MMP-9 and TIMP-2 by
      immunohistochemical staining. The three microcirculation patterns of endothelium
      dependent vessels, mosaic vessels and vasculogenic mimicry were counted. The
      activity of MMP-2, MMP-9 between different groups was examined by gelatin
      zymography. RESULTS: Tumor growth in the three experimental groups was
      statistically significantly slower than that in the control group. The expression
      of MMP-2, MMP-9 and TIMP-2 in each treated group was significantly different with
      that in the control group. The amount of three microcirculation patterns in three
      experimental groups was less than that of the control group, and the amount of MV
      and VM in each experimental group was significantly less than that in the control
      group. By gelatin zymography, the enzyme activity of MMP-9, actived-MMP-2 and MMP
      2/proMMP-2 in ES, DOX and ES + DOX group was lower than that in the control
      group, but the enzyme activity of pro-MMP-2 among the four groups was not
      significantly different. CONCLUSION: The combined use of doxycycline and
      endostatin in melanoma can inhibit the expression of MMPs, influencing the
      formation of different microcirculation patterns in melanoma.

PMID- 18069629
TI  - [Death mode of Hep-3B and A549 tumor cells induced by bluetongue virus strain
      HbC3].
AB  - OBJECTIVE: To study the death mode of human hepatocellular carcinoma Hep-3B cells
      and human lung adenocarcinoma A549 cells induced by bluetongue virus strain HbC3
      (BTV-HbC3) and the mechanism of its action. METHODS: BTV-HbC3 was used to infect
      the tumor cells, and the cytopathic effects (CPE) was observed. TUNEL staining
      was used to detect the apoptosis of tumor cells induced by BTV-HbC3. The changes
      of endoplasmic reticulum and nuclei treated with BTV-HbC3 were further examined
      by laser scanning confocal microscopy. The activities of caspase-3/7, caspase-8
      and caspase-9 were determined by fluorescence analysis. RESULTS: Hep-3B cells
      were sensitive to BTV-HbC3. Lots of early apoptotic cells were found by TUNEL
      staining. The laser scanning confocal microscopic examination showed
      characteristics of apoptosis, such as pyknotic nuclei, margination of nuclear
      chromatin and vacuolization of endoplasmic reticulumin in Hep-3B cells exposed to
      BTV-HbC3. The activity of caspase-3/7 was increased, but the activity changes of
      caspase-8 and caspase-9 were not found. A549 cells were sensitive to BTV-HbC3
      too. But no apoptotic cells were observed by TUNEL staining. The results of laser
      scanning confocal microscopy showed marked vacuolization of endoplasmic
      reticulum, but chromatin margination was not found after A549 cells was exposed
      to BTV-HbC3. The activity of caspase-3/7 and caspase-9 was increased, but the
      activity of caspase-8 was not changed. CONCLUSION: BTV-HbC3 induces apoptosis of
      Hep-3B tumor cells mainly through endoplasmic reticulum signal transduction
      pathway, and the features of cell death in A549 cells could be described as
      paraptosis.

PMID- 18069630
TI  - [Frequent promoter hypermethylation of several tumor suppressor genes in gastric
      carcinoma and foveolar epithelium].
AB  - OBJECTIVE: To study the promoter hypermethylation of several tumor suppressor
      genes in gastric carcinoma (GC) tissue and adjacent normal gastric foveolar
      epithelium (GFE). METHODS: Methylation specific PCR (MSP) was used to examine the
      promoter methylation of tumor suppressor genes E-cadherin, hMLH1, APC and MGMT in
      paraffin-embedded gastric cancer tissue and adjacent normal foveolar epithelium
      in 106 cases. RESULTS: The positive rate of genes promoter methylation was 44.3%
      (47/106 cases) and 72.6% (77/106 cases) at one or more genes tested in the normal
      GFE and GC tissue, respectively. There was a significant difference in the
      positive rates of gene promoter methylation between normal GFE and GC tissue (P =
      0.0001). There was a significant association with Lauren classification, degree
      of differentiation and pTNM staging in GC (P < 0.05), but no significant
      association with Ming's classification (P > 0.05). CONCLUSION: Tumor suppressor
      genes promoter methylation is frequently present in GC and adjacent normal
      gastric foveolar epithelium, especially in Lauren diffuse type GC, poorly
      differentiated GC, mucus-secreting (signet ring) cell GC and pTNM stage III and
      IV GC. Our findings indicate that the gene promoter methylation is a common and
      early event in GC carcinogensis.

PMID- 18069631
TI  - [Expressions and significance of STAT3 and p38 in the carcinogenesis of sporadic
      colorectal tubular adenoma].
AB  - OBJECTIVE: To investigate the possible role of STAT3 and p38 in the
      carcinogenesis of sporadic colorectal tubular adenoma. METHODS: The expression of
      STAT3 and p38 at protein level was studied in 107 sporadic colorectal tubular
      adenomas with different dysplasia (SCTA-D) or with cancerous changes (SCTA-Ca) by
      immunohistochemical staining method, meanwhile the expression of STAT3 at mRNA
      level was detected by in situ hybridization. RESULTS: Immunohistochemical
      staining results showed that the positive expression rate of STAT3 and p38 was
      12.0%, 59.0%, 91.7% and 8.0%, 47.0%, 91.7% in normal colorectal mucosa (NCM),
      SCTA-D and SCTA-Ca, respectively, with a statistically significant difference of
      STAT3 and p38 expression among the SCTA-D, SCTA-Ca and NCM (P < 0.05). The
      expression of STAT3 and p38 was positively correlated with the degree of
      dysplasia from mild to severe SCTA-D (P < 0.05). In situ hybridization results
      showed that the positive expression rate of STAT3 at mRNA level in NCM, SCTA-D
      and SCTA-Ca was 8.00%, 51.8% and 100.0%, respectively, with a statistically
      significant difference among these either (P < 0.05). The positive expression of
      STAT3 at mRNA level was not only positively correlated with the degree of
      dysplasia (P < 0.05), but also with the expression of p38 (P < 0.05). CONCLUSION:
      STAT3 and p38 may be involved in the carcinogenesis of sporadic colorectal
      tubular adenoma.

PMID- 18069632
TI  - [Correlation of tenascin-C degradation fragment with recurrence and/or metastasis
      in early non-small-cell lung cancer].
AB  - OBJECTIVE: To study the correlation of tenascin-c (TN-C) degradation with relapse
      and/or metastasis in stage-I non-small cell lung cancer (NSCLC) in order to
      search for a potential biomarker for predicting recurrence, and also to
      investigate the molecular mechanism of TN-C degradation. Methods The fragment of
      TN-C in 63 surgically treated stage-I NSCLC was detected by Western blotting, and
      the activity of matrix metalloproteinases (MMPs) was also examined by gelatin
      zymography. RESULTS: TN-C degradation fragment was positively detected in 12 of
      63 patients, and 9 of these 12 patients (75.0%) were found to develope recurrence
      during follow-up. The recurrence-free survival at 4 years was 28.1% in patients
      with positive TN-C degradation versus 82.1% in those without (P < 0.001), and
      which was 76.6% at 10 years in the patients without TN-C degradation. The
      activity of MMP-2 in the patients with positive TN-C degradation was also found
      to be significantly higher than that in the patients without (P < 0.001).
      CONCLUSION: Tenascin-c degradation fragment may be a reliable biomarker for
      predicting recurrence and/or metastasis in the early NSCLC, and matrix
      metalloproteinase-2 may be a responsible proteinase for degradation of tenascin
      c.

PMID- 18069633
TI  - [Relationship between serum VEGF level and VEGF, COX-2 and MVD expression in
      breast cancer tissues].
AB  - OBJECTIVE: To investigate the relationship between serum VEGF (sVEGF) level and
      VEGF, COX-2 and MVD expression in breast cancer, and to discuss their role in
      angiogensis of breast cancer. METHODS: sVEGF level was detected by ELISA in 68
      preoperative breast cancer, 35 benign breast disease and 20 healthy women. The
      expression of VEGF, COX-2 and MVD was detected by immunohistochemical method in
      tissues of breast cancer and breast benign diseases, and to analyze the
      relationship of sVEGF, VEGF, COX-2 and MVD. RESULTS: (1) sVEGF level in
      preoperative breast cancers was 306.51 pg/ml (interquartile range from 190.44 to
      442.04 pg/ml), in benign diseases was 150.82 pg/ml (interquartile range from
      82.36 to 212.34 pg/ml), and in healthy control was 105.93 pg/ml (interquartile
      range from 78.54 to 157.77 pg/ml). The sVEGF level of preoperative breast cancer
      group was significantly higher than that of breast benign disease group and
      healthy women (P = 0.001). (2) The VEGF expression positive rate in breast cancer
      (67.65%) was significantly higher than that in breast benign disease (44.12%) (P
      = 0.015). The COX-2 expression positive rate in breast cancer (42.86%) was
      significantly higher than that in breast benign disease (11.43%) (P = 0.002). (3)
      the COX-2 expression positive rate in sVEGF high level patients (56.00%) was
      significantly higher than that in sVEGF normal level patients (11.11%) (P =
      0.024), and MVD in sVEGF high level patients (27.32 +/- 3.40) was also higher
      than that in sVEGF normal level patients (15.31 +/- 6.16) (P = 0.011). (4) The
      sVEGF level (322.09 +/- 79.31) of 68 breast cancer patients whose VEGF was
      positive in breast cancer tissues was significantly higher than that in VEGF
      negative group (222.47 +/- 73.53) (P = 0.017). (5) The COX-2 expression positive
      rate in VEGF positive expression group (65.21%) was significantly higher than
      that in VEGF negative expression group (18.18%) (P = 0.017). The MVD expression
      in COX-2 positive expression group (22.94 +/- 5.51) was significantly higher than
      that in COX-2 negative expression group (10.30 +/- 4.42) (P = 0.027). CONCLUSION:
      sVEGF level in breast cancer is significantly higher than that in breast benign
      disease and healthy women, and is correlated with the expression of COX-2 and MVD
      in breast cancer tissues.

PMID- 18069634
TI  - [Expression of COX-2 and MMP-9 in cervical carcinoma and their clinical
      significance].
AB  - OBJECTIVE: To investigate the expressions of COX-2 and MMP-9 in cervical
      carcinoma and their clinical significance. METHODS: Immunohistochemical SP method
      was used to detect the expressions of COX-2 and MMP-9 in 72 cases of invasive
      carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from
      tumor (NCE), and the relationship between the expressions of COX-2 and MMP-9 in
      ICC and some factors relating to clinical pathology of cervical carcinoma such as
      histopathological grading, lymph node metastasis, stroma involvement and FIGO
      staging were analyzed statistically. RESULTS: The rates of positive expression of
      COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9%
      in group ICC and 12.5% in group NCE, P = 0.000. MMP-9: 94.4% in group ICC and
      43.8% in group NCE, P = 0.000. The expression of COX-2 was positively correlated
      with lymph node metastasis and stroma involvement (r = 0.296, P = 0.012 in group
      ICC and r = 0.257, P = 0.029 in group NCE, respectively). The expression of MMP-9
      was positively correlated with FIGO staging (r = 0.329, P = 0.005) and
      histopathological grading (r = 0.351, P = 0.003). The expression of COX-2 was
      positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011).
      CONCLUSION: The overexpressions of COX-2 and MMP-9 are closely related to the
      invasion and growth of cervical carcinoma. The tissue with overexpression of COX
      2 has strong invasion ability. COX-2 and MMP-9 have synergistic effect on
      proliferation, invasion and metastasis of cancer cells. Detecting the expression
      of both COX-2 and MMP-9 may be of value in further understanding the biological
      behavior and predicting the prognosis of cervical carcinoma.

PMID- 18069635
TI  - [Clinical analysis of primary mediastinal germ cell tumors].
AB  - OBJECTIVE: To investigate the clinical and pathological features, optimal
      treatment and prognostic factor in primary mediastinal germ cell tumors (PMGCT).
      METHODS: The clinical presentation, pathological features and therapeutic results
      of 29 patients with PMGCT were retrospectively analyzed. RESULTS: All the 29
      patients were male with a mean age of 26.1 +/- 9.6 years at diagnosis. All tumors
      were originated from the anterior mediastinum with a mean diameter of 16.0 +/-
      5.2 cm. There were 5 (17.2%) primary mediastinal seminomas (PMSGCT) and 24
      (82.8%) primary mediastinal nonseminomas (PMNSGCT) in this series. Dyspnea, cough
      and chest pain were the most common symptoms. Multimodality treatment consisting
      of cisplatin-based chemotherapy, surgery and radiotherapy was the principal
      therapy for PMGCT patients. The median survival of the 24 PMNSGCT patients was
      19.0 months with 1-, 2-year survival rate of 65.3% and 28.1%, respectively;
      whereas the median survival of the 5 PMSGCT patients has not reached but longer
      with significant differences (P = 0.008). Cox multivariate analysis indicated
      that limited mediastinal disease at diagnosis (P = 0.004) and the use of
      cisplatin-based combined chemotherapy (P = 0.005) were independent good
      prognostic factors of PMNSGCT. CONCLUSION: Primary mediastinal nonseminoma
      constitutes the most of primary mediastinal germ cell tumors. Cisplatin-based
      combined chemotherapy may be the most effective for the treatment of primary
      mediastinal germ cell tumors. The prognosis of primary mediastinal nonseminomas
      is significantly worse than that of primary mediastinal seminomas, and correlated
      with the extent of disease and chemotherapy.

PMID- 18069636
TI  - [Clinical features of patients with metastasis in phalanges as first symptom of
      primary lung cancer].

PMID- 18069637
TI  - [Comparison of 18F-FDG coincidence SPECT imaging and computed tomography in the
      initial staging and therapeutic evaluation of lymphomas].
AB  - OBJECTIVE: To investigate the clinical value of 18F-fluorodeoxyglucose (18F-FDG)
      coincidence SPECT imaging versus computed tomography (CT) for malignant lymphoma
      in the initial staging, early response to therapy, evaluation after completion of
      therapy and long-term follow-up. METHODS: 18F-FDG SPECT scans was performed on 61
      patients with pathologically proven malignant lymphoma. The mean age of this
      series was 55 years ranged from 12 to 85 years. The data of these patients were
      retrospectively analyzed, and the result of 18F-FDG SPECT scan was compared with
      the CT imaging result performed within 2 weeks before or after FDG scan. 161 18F
      FDG SPECT scans were performed for initial tumor staging (n=61), early response
      to therapy (n=42), evaluation after completion of therapy (n=26) and long-term
      follow-up (n=32). Each patient had a follow-up >6 months. RESULTS: (1) Compared
      with CT scan, 18F-FDG SPECT imaging accurately upstaged the disease for 34.4%
      (21/61) of these patients at initial staging. It detected the lesions which were
      undetected by CT including bone marrow infiltration (n=17), foci of lymph node
      (n=3) and liver involvement (n=1). However, 3 patients were incorrectly staged,
      either downstaged or upstaged by 18F-FDG SPECT imaging. Of 212 lesions in 61
      patients, 18-FDG SPECT imaging detected more lesions than CT (P < 0.01). The
      correspondence rate of '18-FDG SPECT imaging with marrow histology was 80.3%
      (49/61). (2) In early evaluation of the response to treatment, the accuracy,
      positive predictive value and negative predictive value of 18F-FDG SPECT imaging
      was 85.7%, 92.0% and 76.5% respectively, which is much higher than that of CT
      (64.3%, 75.0% and 50.0%), therefore, the therapeutic scheme in 21.4% (9/42) of
      these patients was changed by 18F-FDG SPECT imaging. Of 17 cases with negative
      18F-FDG SPECT scan in early evaluation of therapy, clinical remission (13
      complete remission and 3 partial remission) were achieved in 16 patients. Of the
      25 patients with positive ones, 13 were considered as having progressive disease.
      (3) In the evaluation at the end of therapy or during follow-up, 58 18F-FDG SPECT
      imagings were performed in 26 patients. The specificity and positive predictive
      value were 85.7% and 68.4% versus 59.5% and 43.3%, respectively, by CT scan. Of
      14 patients with residual masses detected by CT scan, 8 were diagnosed as
      complete remission (CR) by 18F-FDG SPECT imaging based on persistently negative
      FDG scans; The other 6 were interpreted as CR (n=1), partial remission (PR, n=2),
      non-remission (n=1) and progressive disease (n=2), thus there was only one false
      positive FDG scan in these 14 patients. CONCLUSION: 18F-FDG imaging is quite
      effective and superior to CT scan for malignant lymphoma in initial staging,
      evaluation of early response to therapy and after completion of therapy, and long
      term follow-up, especially for evaluating the residual masse.

PMID- 18069638
TI  - [Postoperative radiotherapy for primary intraosseous carcinoma of the jaws].
AB  - OBJECTIVE: To investigate the indication, location and dose of postoperative
      radiotherapy for primary intraosseous carcinoma (PIOC) of the jaws. METHODS: From
      October 1969 to November 2005, 13 patients with PIOC were treated at the Cancer
      Hospital of Chinese Academy of Medical Sciences. Forty six cases with complete
      clinical data were collected from 27 published reports. Twenty-seven of the 59
      patients were treated with surgery plus postoperative radiotherapy, and 22 with
      surgery alone. RESULTS: All of the 13 cases in our series had advanced disease,
      and overall 1-, 2- and 3-year survival rats were 59.2%, 33.8% and 12.7% ,
      respectively. For the reported 59 cases in literature, the overall 1-, 2- and 3
      year survival rats were 78.4%, 53.9% and 34.0%, respectively. They were 84.3%,
      57.2% and 43.6% for the patients treated by surgery plus postoperative
      radiotherapy, whereas they were 81.8%, 71.2% and 35.1% for the patients by
      surgery alone (P = 0.908). It seemed that surgery plus postoperative radiotherapy
      could not improve the survival of PIOC patients with involvement of adjacent soft
      tissues or positive neck nodes or partial excision of primary tumor when compared
      with surgery alone, if the bias of selection in the patients for postoperative
      radiotherapy was neglected. CONCLUSION: Postopreative radiotherapy may improve
      the survival for the patient with primary intraosseous carcinoma of the jaws. Our
      suggestion is that postoperative radiotherapy should be applied to the patient
      with any of the following items: positive operative margin; tumor involvement of
      adjacent soft-tissues; positive neck nodes; partial excision of primary tumor.
      However, the location and dose of postoperative radiotherapy may be varying at
      different situation.

PMID- 18069639
TI  - [New trends in research on cancer genomics].

PMID- 18069640
TI  - [Whole brain irradiation for non-small-cell lung cancer with brain metastasis].
AB  - OBJECTIVE: To investigate the time of whole brain irradiation and the prognostic
      factors for non-small lung cancer patients with brain metastasis. METHODS: From
      August 1996 to December 2003, 147 patients with brain metastasis from non-small
      cell lung cancer received whole brain irradiation. The patients were divided into
      two groups: with or without symptoms caused by brain metastasis, each group was
      then divided into two sub-groups, early whole brain irradiation group (the
      interval between the diagnosis of brain metastasis and the brain irradiation < or
      = one month) and late group ( the interval > one month ). Univariate and
      multivariate analysis (Cox regression) as well as Kaplan-Meier method in SPSS
      software package 11.5 was used to analyze the data of the 147 patients including
      72 with brain metastasis symptom and 75 without. RESULTS: The median survival
      time (MS) of patients with or without extracranial metastasis was 9.9 months and
      11.3 months (P = 0.0002). Multivariate analysis indicated that extracranial
      metastasis was an independent prognostic factor (P = 0.0004). For 72 patients
      with brain metastasis symptom, the MS of the patients with and without
      extracranial metastasis was 9.3 months and 11.3 months (P = 0.0036). The MS of
      patients with early and late whole brain irradiation was 11.4 months and 9.2
      months (P = 0.001). Multivariate analysis showed that extracranial metastasis,
      the interval between the diagnosis of brain metastasis and the whole brain
      irradiation were independent prognostic factors. However, for 75 patients without
      brain metastasis symptom, the MS difference of those with early or late whole
      brain irradiation was not statistically significant (P = 0.1643). CONCLUSION: The
      extracranial metastasis in non-small cell lung cancer patients with brain
      metastasis is an independent prognostic factors. Early whole brain irradiation
      may improve the survival for those with brain metastasis symptoms.

PMID- 18069641
TI  - [Gefitinib in the treatment of male patients with advanced non-small-cell lung
      cancer].
AB  - OBJECTIVE: To investigate the antitumor efficacy, time to tumor progression (TTP)
      and toxicity of gefitinib (Iressa, ZD1839)--a selective epidermal growth factor
      receptor tyrosine kinase inhibitor in the treatment of male patients with
      advanced non-small-cell lung cancer (NSCLC). Methods Fifty-nine male patients
      with stage IV NSCLC orally took Iressa 250 mg once daily until disease
      progression or intolerable toxicity ocurred. They were required to conduct tumor
      evaluation before the treatment, one month after Iressa administration and then
      every other month. RESULTS: Of these 59 patients, no complete regression was
      observed, 23.7% had partial response (PR), and 16.9% stable disease (SD) with a
      disease control (PR + SD) rate of 40.7%, while 59.3% had progress of disease
      (PD). The median time to tumor progression (TTP) was 1.8 months, and the median
      survival was 8.5 months. Fifty-nine patients were followed up over one year, 35
      over two year and 15 over three year, and the 1-, 2- and 3-year survival rates
      were 42.4%, 17.1% and 13.3%. The most common adverse effects were grade 1 or 2
      skin reaction and diarrhea. CONCLUSION: Iressa is effective in antitumor for the
      male patients with advanced non-small-cell lung cancer, and can improve the
      survival for those responsing to gefitinib. The adverse effects are usually
      tolerable.

PMID- 18069642
TI  - [Surgical treatment for colorectal cancer with simultaneous hepatic metastasis].
AB  - OBJECTIVE: To investigate the indication of surgical treatment for primary
      colorectal carcer with simultaneous hepatic metastasis. METHODS: 116 colorectal
      cancer patients with simultaneous hepatic metastasis underwent surgery from
      January 1990 to December 2001. The data were analyzed using Statistical Package
      for the Social Sciences (Release 11.5, SPSS, Inc). The survival was estimated
      using Kaplan-Meier method, and the survival comparison was carried out using the
      log-rank test. Multivariate analysis was performed using Cox regression. RESULTS:
      Totally, 116 patients received surgical resection for primary colorectal tumor,
      18 of them underwent liver metastasis resection simultaneously. Postoperative
      complication developed in 14.7% of these patients with postoperative death in two
      patients. The overall 5-year survival rate was 14.29%. The 5-year survival rate
      of those who had liver metastasis resection was 32.12%. Multivariate analysis
      showed that liver metastasis resection, abdominal carcinomatosis, chemotherapy
      and intervention treatment were the most important prognostic factors.
      CONCLUSION: Surgical resection of primary colorectal cancer with simultaneous
      resection of liver metastasis or with combined modality therapies such as
      chemotherapy and intervention treatment is effective to prolong patient's
      survival for primary colorectal cancer patient with simultaneous hepatic
      metastasis.

PMID- 18069643
TI  - [Comparison of monolayer wide-edge continuous suture anastomosis with regular
      interrupted suture anastomosis at esophagogastrostomy for esophageal cancer].
AB  - OBJECTIVE: To evaluate the monolayer wide-edge continuous suture anastomosis in
      order to explore the method to prevent or reduce the frequency of anastomotic
      fistula and stenosis. METHODS: 936 esophageal cancer patients were divided into
      two groups: 468 by monolayer wide-edge continuous suture anastomosis with
      absorbable suture at esophagogastrostomy; while the other 468 by regular
      interrupted suture anastomosis with silk thread as control. The complication such
      as anastomotic fistula and stenosis in two groups were compared. RESULTS: In the
      group treated by monolayer wide-edge continuous suture anastomosis, there were 1
      fistula (0.2%) and 1 stenosis (0.2%) versus 8 fistula (1.9%) and 11 stenosis
      (2.4%) in the control group. There was a statistically significant difference
      between two guoups was observed (P < 0.05). CONCLUSION: Monolayer wide-edge
      continuous suture anastomosis at esophagogastrostomy for esophageal cancer
      patient may effectively prevent or reduce the frequency of anastomotic fistula
      and stenosis.

PMID- 18069644
TI  - Microbially derived off-flavor from geosmin and 2-methylisoborneol: sources and
      remediation.
AB  - Microbially derived off-flavors can adversely affect the beverage, food, water,
      and aquaculture industries. Off-flavor can temporarily be controlled by adopting
      best management practices such as proper aeration, liming, and dredging, and,
      more importantly, by avoidance of excessive nutrient use. Research studies focus
      on the effective means of control with the major emphasis on controlling the odor
      causing algae populations and developing effective and selective algicides, which
      are not always available for use at the right time and can also have adverse
      impacts on the environment. Furthermore, selective application of synthetic
      algicides is not always recommended for reasons of inconsistency in the results
      and concerns regarding the frequent use of these chemicals, such as toxicity,
      accumulation of free copper, dissolved oxygen voids, increase in toxic ammonia
      and hydrogen sulfide, pH fluctuation, reduced photosynthetic activity, and
      reestablishment of algae in nutrient-rich water, thus requiring multiple
      treatments. Conversely, the plant-derived products appear to be environmentally
      safe and economical in view of their abundant availability and easy operational
      process. However, there needs to be more extensive work in this field. Precursors
      of sesquiterpene synthesis may selectively help to suppress off-flavor-producing
      species. Bioremedial measures by means of microbial degradation and gene
      bioaugmentation may be promising and are the subjects of much future research for
      effective controls.

PMID- 18069645
TI  - Mercury in the San Francisco Estuary.
AB  - This review presents some of the published and other important literature on
      mercury contamination in San Francisco Estuary. Studies on human consumption of
      contaminated sportfish and on detecting ecological impacts of this contamination
      in wetland areas validate concerns regarding mercury's toxicity in this system.
      Mining, industrial, and environmental uses of mercury have occurred for more than
      a century, resulting in its large historic and continuing transport to the
      estuary. Consequently, there is a widespread distribution in the estuary, but
      more work is needed to show its relative chemical and biological availability
      from these sources. The uptake of mercury in the estuary has been shown in
      phytoplankton, but studies on biomagnification in local food webs have yet to
      draw a clear path to impairment in sportfish and waterbirds. In light of these
      concerns of impairment and the need for further information, large restoration
      activities planned for the estuary will require new technical approaches to solve
      important management questions, such as the location of key areas of
      methylmercury production.

PMID- 18069646
TI  - DDE remediation and degradation.
AB  - DDT and its metabolites, DDD and DDE, have been shown to be recalcitrant to
      degradation. The parent compound, DDT, was used extensively worldwide starting in
      1939 and was banned in the United States in 1973. The daughter compound, DDE, may
      result from aerobic degradation, abiotic dehydrochlorination, or photochemical
      decomposition. DDE has also occurred as a contaminant in commercial-grade DDT.
      The p,p'-DDE isomer is more biologically active than the o,p-DDE, with a reported
      half-life of -5.7 years. However, when DDT was repeatedly applied to the soil,
      the DDE concentration may remain unchanged for more than 20 yr. Remediation of
      DDE-contaminated soil and water may be done by several techniques.
      Phytoremediation involves translocating DDT, DDD, and DDE from the soil into the
      plant, although some aquatic species (duckweed > elodea > parrot feather) can
      transform DDT into predominantly DDD with some DDE being formed. Of all the
      plants that can uptake DDE, Cucurbita pepo has been the most extensively studied,
      with translocation values approaching "hyperaccumulation" levels. Soil moisture,
      temperature, and plant density have all been documented as important factors in
      the uptake of DDE by Cucurbita pepo. Uptake may also be influenced positively by
      amendments such as biosurfactants, mycorrhizal inoculants, and low molecular
      weight organic acids (e.g., citric and oxalic acids). DDE microbial degradation
      by dehalogenases, dioxygenases, and hydrolases occurs under the proper
      conditions. Although several aerobic degradation pathways have been proposed,
      none has been fully verified. Very few aerobic pure cultures are capable of fully
      degrading DDE to CO2. Cometabolism of DDE by Pseudomonas sp., Alicaligens sp.,
      and Terrabacter sp. grown on biphenyl has been reported; however, not all
      bacterial species that produce biphenyl dioxygenase degraded DDE. Arsenic and
      copper inhibit DDE degradation by aerobic microorganisms. Similarly, metal
      chelates such as EDTA inhibit the breakdown of DDE by the extracellular
      lignolytic enzymes produced by white rot fungi. The addition of adjutants such as
      sodium ion, surfactants, and cellulose increased the rate of DDT aerobic or
      anaerobic degradation but did little to enhance the rate of DDE disappearance
      under anaerobic conditions. Only in the past decade has it been demonstrated that
      DDE can undergo reductive dechlorination under methanogenic and sulfidogenic
      conditions to form the degradation product DDMU, 1-chloro-2,2'-bis-(4'
      chlorophenyl)ethane. The only pure culture reported to degrade DDE under
      anaerobic conditions was the denitrifier Alcaligens denitrificans. The
      degradation of DDE by this bacterium was enhanced by glucose, whereas biphenyl
      fumes had no effect. Abiotic remediation by DDE volatilization was enhanced by
      flooding and irrigation and deepplowing inhibited the volatilization. The use of
      zero-valent iron and surfactants in flooded soils enhanced DDT degradation but
      did not significantly alter the rate of DDE removal. Other catalysts (palladized
      magnesium, palladium on carbon, and nickel/aluminum alloys) degraded DDT and its
      metabolites, including DDE. However, these systems are often biphasic or involve
      explosive gases or both. Safer abiotic alternatives use UV light with titanium
      oxide or visible light with methylene green to degrade DDT, DDD, and DDE in
      aqueous or mixed solvent systems. Remediation and degradation of DDE in soil and
      water by phytoextraction, aerobic and anaerobic microorganisms, or abiotic
      methods can be accomplished. However, success has been limited, and great care
      must be taken that the method does not transfer the contaminants to another
      locale (by volatilization, deep plowing, erosion, or runoff) or to another
      species (by ingestion of accumulating plants or contaminated water). Although the
      remediation of DDT-, DDD-, and DDE-contaminated soil and water is beset with
      myriad problems, there remain many open avenues of research.

PMID- 18069647
TI  - Surfactant effects on environmental behavior of pesticides.
AB  - The potential effects of adjuvants, including surfactants used in pesticide
      formulation, have been extensively studied for many small organic chemicals, but
      similar investigation on pesticides is limited in most cases. Solubilizing
      effects leading to the apparently increased water solubility of a pesticide are
      commonly known through the preparation of formulations, but fundamental profiles,
      especially for a specific monodisperse surfactant, are not fully studied. Reduced
      volatilization of a pesticide from the formulation can be explained by analogy of
      a very simple organic chemical, but the actual mechanism for the pesticide is
      still obscure. In contrast, from the point of view of avoiding groundwater
      contamination with a pesticide, adsorption/desorption profiles in the presence of
      surfactants and adjuvants have been examined extensively as well as pesticide
      mobility in the soil column. The basic mechanism in micelle-catalyzed hydrolysis
      is well known, and theoretical approaches including the PPIE model have succeeded
      in explaining the observed effects of surfactants, but its application to
      pesticides is also limited. Photolysis, especially in an aqueous phase, is in the
      same situation. The dilution effect in the real environment would show these
      effects on hydrolysis and photolysis to be much less than expected from the
      laboratory basic studies, but more information is necessary to examine the
      practical extent of the effects in an early stage of applying a pesticide
      formulation to crops and soil. Many adjuvants, including surfactants, are
      biodegradable in the soil environment, and thus their effects on the
      biodegradation of a pesticide in soil and sediment may be limited, as
      demonstrated by field trials. Not only from the theoretical but also the
      practical aspect, the foliar uptake of pesticide in the presence of adjuvants has
      been investigated extensively and some prediction on the ease of foliar uptake
      can be realized in relation to the formulation technology. However, effect on
      root uptake of pesticides is to be further investigated. In an aqueous
      environment more or less contaminated by various chemicals such as detergents and
      their degradates, it is necessary to investigate the effect of adjuvants on
      uptake, bioconcentration, and trophic transfer of pesticides for better
      understanding of pesticide contamination of aquatic species in the aquatic
      environment.

PMID- 18069648
TI  - Pre-eclampsia is associated with dendritic cell recruitment into the uterine
      decidua.
AB  - Pre-eclampsia is a leading cause of fetal and maternal morbidity and mortality
      that preferentially affects primiparous patients. It is associated with systemic
      inflammation and impaired trophoblast invasion of the decidua. Decidual cells are
      the major cell type of the pregnant endometrium. Macrophages and dendritic cells
      are major specialized antigen-presenting cells that promote both innate immunity
      and immune tolerance. Macrophage infiltration is implicated in impaired
      trophoblast invasion that leads to pre-eclampsia. By contrast, the potential
      modulating role of decidual dendritic cells in the genesis of pre-eclampsia has
      not been investigated. Interleukin-1beta (IL-1beta), a pro-inflammatory cytokine,
      has been implicated in the genesis of pre-eclampsia. Thus, we postulate that pre
      eclampsia would be associated with enhanced decidual dendritic cells infiltration
      and that IL-1beta would enhance the production of relevant dendritic cell
      recruiting chemokines. We used immunohistochemistry to demonstrate a marked
      infiltrate of immature and mature dendritic cells in pre-eclamptic decidua.
      Further, immunohistochemistry and immunoassays of placental bed biopsies revealed
      that pre-eclamptic decidua displays elevated levels of several monocyte- and
      dendritic cell-recruiting chemokines. Leukocyte-free first-trimester decidual
      cells were then treated with IL-1beta, which enhanced the mRNA and protein
      expression of these chemokines. The current study also confirmed previous reports
      that macrophages directly impaired trophoblast invasion and that this inhibitory
      effect is augmented by the conditioned medium of IL-1beta-treated first-trimester
      decidual cells. However, unlike macrophages, dendritic cells did not directly
      impede trophoblast invasion. This study demonstrates that the inflammatory milieu
      of pre-eclampsia induces decidual cells to promote dendritic cell infiltration.
      Given their unusual versatility in mediating both immunity and tolerance, these
      novel findings suggest that dendritic cells may play a critical role either in
      the pathogenesis of pre-eclampsia or its prevention in subsequent pregnancies.

PMID- 18069649
TI  - Effects on litter-dwelling earthworms and microbial decomposition of soil-applied
      imidacloprid for control of wood-boring insects.
AB  - BACKGROUND: Imidacloprid is an effective, systemic insecticide for the control of
      wood-boring insect pests in trees. Systemic applications to trees are often made
      by soil injections or drenches, and the resulting imidacloprid concentrations in
      soil or litter may pose a risk of harm to natural decomposer organisms. The
      authors tested effects of imidacloprid on survival and weight gain or loss of the
      earthworms Eisenia fetida (Savigny) and Dendrobaena octaedra (Savigny), on leaf
      consumption rates and cocoon production by D. octaedra and on microbial
      decomposition activity in laboratory microcosms containing natural forest litter.
      RESULTS: Dendrobaena octaedra was the most sensitive of the two earthworm
      species, with an LC(50) of 5.7 mg kg(-1), an LC(10) of about 2 mg kg(-1) and
      significant weight losses among survivors at 3 mg kg(-1). Weight losses resulted
      from a physiological effect rather than from feeding inhibition. There were no
      effects on cocoon production among survivors at 3 mg kg(-1). The LC(50) for E.
      fetida was 25 mg kg(-1), with significant weight losses at 14 mg kg(-1). There
      were no significant effects on microbial decomposition of leaf material at the
      maximum test concentration of 1400 mg kg(-1). CONCLUSION: The results indicate
      that, when imidacloprid is applied as a systemic insecticide to the soil around
      trees, it is likely to cause adverse effects on litter-dwelling earthworms if
      concentrations in the litter reach or exceed about 3 mg kg(-1).

PMID- 18069650
TI  - In vitro antimicrobial and in vivo antioomycete activities of the novel
      antibiotic thiobutacin.
AB  - BACKGROUND: A number of synthetic fungicides are not effective when confronted by
      oomycete pathogens because many fungicide targets are absent from oomycetes.
      Moreover, resistance to fungicides has already arisen in oomycete species, and
      thus development of new, effective and safe compounds for use in oomycete disease
      control is necessary. RESULTS: Zoospore lysis began at 10 microg mL(-1) of
      thiobutacin, and most of the zoospores were collapsed at 50 microg mL(-1).
      Thiobutacin also revealed inhibitory activity against the cyst germination and
      hyphal growth of Phytophthora capsici at 50 microg mL(-1). Treatment with
      thiobutacin exhibited protective activity against development of Phytophthora
      disease on pepper plants. CONCLUSION: The authors verified in vitro antioomycete
      activity of thiobutacin against P. capsici and its control efficacy against
      Phytophthora blight in vivo. This is the first report to demonstrate in vivo
      antioomycete activity of the novel antibiotic thiobutacin against P. capsici
      infection.

PMID- 18069651
TI  - New multiple-herbicide crop resistance and formulation technology to augment the
      utility of glyphosate.
AB  - Glyphosate has performed long and well, but now some weed communities are
      shifting to populations that survive glyphosate, and growers need new weed
      management technologies to augment glyphosate performance in glyphosate-resistant
      crops. Unfortunately, most companies are not developing any new selective
      herbicides with new modes of action to fill this need. Fortunately, companies are
      developing new herbicide-resistant crop technologies to combine with glyphosate
      resistance and expand the utility of existing herbicides. One of the first
      multiple-herbicide-resistant crops will have a molecular stack of a new
      metabolically based glyphosate resistance mechanism with an active-site-based
      resistance to a broad spectrum of ALS-inhibiting herbicides. Additionally, new
      formulation technology called homogeneous blends will be used in conjunction with
      glyphosate and ALS-resistant crops. This formulation technology satisfies
      governmental regulations, so that new herbicide mixture offerings with diverse
      modes of action can be commercialized more rapidly and less expensively.
      Together, homogeneous blends and multiple-herbicide-resistant crops can offer
      growers a wider choice of herbicide mixtures at rates and ratios to augment
      glyphosate and satisfy changing weed management needs.

PMID- 18069652
TI  - Combined effects of termiticides and mechanical stress on chlorinated polyvinyl
      chloride (CPVC) pipe.
AB  - BACKGROUND: CPVC pipe failures have recently been reported beneath structures as
      a result of termiticide soil treatments. To determine whether these CPVC failures
      were actually caused by termiticides, CPVC tubes were filled with 50 mL of either
      termiticide concentrate, dilutions or treated builder's sand and sealed.
      Mechanical stress was added to these sealed tubes by hanging bricks from their
      ends. RESULTS: As concentrates, eight of nine emulsifiable concentrates tested
      caused failure within 8 weeks. None of the three suspensible concentrates tested
      caused failure over this period. Dilution of emulsifiable concentrates caused
      progressively fewer CPVC tube failures. No treated soils caused tube failures.
      Excessive CPVC glue applications in combination with chlorpyrifos 440 g kg(-1) EC
      (Dursban(trade mark) TC) degraded the CPVC. All volatile organic compounds (VOCs)
      found in the termiticide formulations caused CPVC tube failure within 1 week as
      pure chemicals. The VOC 1,3,5-trimethylbenzene caused CPVC tube failure within
      minutes of exposure. This VOC was found in all termiticides that caused failures
      as concentrates. CONCLUSION: It is highly improbable that a properly conducted
      preconstruction soil treatment, where termiticide is completely adsorbed to the
      soil, would be solely responsible for CPVC pipe failure. Manufacturers should
      consider removing 1,3,5-trimethylbenzene from termiticide formulations to
      minimize the risk of CPVC pipe failure.

PMID- 18069653
TI  - The benefits of combining elemental sulfur with a DMI fungicide to control
      Monilinia fructicola isolates resistant to propiconazole.
AB  - BACKGROUND: Management of demethylation inhibitor (DMI) fungicide resistance in
      Monilinia fructicola (G. Winter) Honey is a priority in peach orchards of the
      southeastern United States, but DMI fungicides are still an important component
      of antiresistance strategies in view of the few effective alternatives. The goal
      of this study was to investigate potential benefits of a sulfur/propiconazole
      mixture for the control of propiconazole-resistant isolates. RESULTS: The mixture
      provided the best control for propiconazole-resistant isolates, regardless of
      protective or curative application timings, or the presence or absence of fruit
      injury. Propiconazole-resistant isolates developed disease on detached fruit
      after protective or curative applications of propiconazole or its mixture with
      sulfur, but protective applications of the mixture significantly reduced (P =
      0.05) disease symptoms compared with the individual compounds. Additive to
      slightly synergistic effects were observed for the mixture in protective
      treatments of peaches inoculated with propiconazole-resistant isolates.
      CONCLUSION: The results suggest that the addition of elemental sulfur to a DMI
      fungicide is likely to be a relatively inexpensive means to improve brown rot
      control in peach production areas where reduced sensitivity to DMI fungicides is
      suspected but has not led to noticeable control failure.

PMID- 18069654
TI  - Evaluation of sticky traps and insecticides to prevent gall induction by
      Gynaikothrips uzeli Zimmerman (Thysanoptera: Phlaeothripidae) on Ficus benjamina.
AB  - BACKGROUND: Gynaikothrips uzeli Zimmerman was first detected in North America
      from galls on weeping fig (Ficus benjamina L.) in 2003. It has been reported from
      ten states in the continental United States, Hawaii, Trinidad and Costa Rica.
      Adult thrips induce leaves to fold permanently along the midvein, making it a
      significant pest of weeping fig. Studies were initiated to determine monitoring
      methods and establish control recommendations. RESULTS: Comparison of captures of
      adult G. uzeli on blue, yellow, white and green sticky traps found yellow to be
      the most effective color. Yellow traps were effective for capturing adult
      Thripastichus gentilei (del Guercio), a larval parasitoid of G. uzeli. Thrips
      were first captured around 10:00 h. Captures peaked around 15:00-16:00 h and
      typically ceased by 21:00 h. Systemic neonicotinoid insecticides applied to
      container media were ineffective against adult G. uzeli feeding on foliage, and
      foliar applications of these products provided < or =7 days control. Conventional
      products provided satisfactory control after 1 day, but efficacy declined
      thereafter. Bifenthrin provided > or = 14 days residual control of adults.
      CONCLUSION: This paper represents the first report of monitoring phlaeothripids
      with sticky traps. Data from multiple trials suggest that products effective
      against other thrips have limited use against G. uzeli.

PMID- 18069655
TI  - Residue distribution of the acaricide coumaphos in honey following application of
      a new slow-release formulation.
AB  - Acaricide used in beehives for the control of varroa often leaves residues in bee
      products. The behaviour and distribution of the acaricide coumaphos in honey
      following the application of a new slow-release strip formulation (CheckMite+)
      was assessed. The bee colonies were allowed to build new combs without
      foundation, and two strips were hung in the brood chamber of each colony for a
      period of 42 days. The distribution of coumaphos residues in honey in relation to
      the position of the frame and the duration of treatment was examined by
      collecting samples from each comb at various time intervals up to 145 days after
      treatment. In the brood chamber, coumaphos was incorporated into honey from the
      first day of application, and residues accumulated mainly in combs placed next to
      strips. In the adjacent combs, residues remained at low concentrations with
      slight variations. In the honey chamber, residue concentrations on the day of
      strip removal ranged between 0.006 and 0.020 mg kg(-1), while 79 days after
      application the concentration of coumaphos residues was below 0.020 mg kg(-1).
      Residues above the EC fixed maximum residue limit (MRL) of 0.1 mg kg(-1) were
      measured only in brood chamber honey obtained from those combs placed next to
      strips. In these samples, 0.060-0.111 mg kg(-1) of coumaphos was detected up to
      103 days after strip removal. Coumaphos residues in honey extracted from combs
      that were placed at the edge of the brood chamber were found below the MRL value,
      even during the 42 day period of CheckMite+ strip treatment.

PMID- 18069656
TI  - Suitability of two laboratory testing methods to evaluate the side effects of
      pesticides on Typhlodromus pyri Scheuten (Acari: Phytoseiidae).
AB  - BACKGROUND: Laboratory results of the French ANPP/CEB guideline No. 167 and
      IOBC/WPRS Ring Testing Group methods for testing the side effects of pesticides
      on the predatory mite Typhlodromus pyri Scheuten were compared with respect to
      their suitability to evaluate the toxicity of three pesticides. RESULTS: Results
      obtained with the ANPP/CEB guideline allow the demonstration of significant
      differences between two slightly toxic products, a dichlofluanid 500 g kg(-1) kWP
      (Euparen) 50WP) and a quinoxyfen 250 g L(-1) SCC (Legend), and a highly toxic
      cymoxanil 60/mancozeb 200/folpet 275 g kg(-1) WP [Remiltine F Pepite) (RFP)], on
      the basis of bioassays conducted in the laboratory. In contrast, results obtained
      with the IOBC/WPRS method classified all three as harmful. CONCLUSION: The
      evaluation of the toxicity of RFP revealed that the concentration, the quantity
      of the wet deposit and the food source used in the IOBC/WPRS method maximise the
      toxicity, in comparison with those used in the ANPP/CEB protocol. Valid criteria
      in controls were all respected in the ANPP/CEB tests but not in the IOBC/WPRS
      samples. This result revealed difficulties related to the use of the IOBC/WPRS
      method in laboratories.

PMID- 18069657
TI  - Inhibitory activity against plant pathogenic fungi of extracts from Myoporum
      bontioides A. Gray and indentification of active ingredients.
AB  - BACKGROUND: In order to understand the bioactivity of Myoporum bontioides A. Gray
      against plant pathogens and determine its active ingredients, the inhibitory
      activities of methanol extracts from M. bontioides against Fusarium oxysporum f.
      sp. niveum (E. F. Smith) Snyder & Hansen, Pestalotia mangiferae P. Henn.,
      Thielaviopsis paradoxa (De Seynes) v. Hohnel, Colletotrichum musae (Berk. & M. A.
      Curtis) v. Arx, Alternaria alternata (Fr.) Keissler, Mycosphaerella sentina (Fr.)
      Schroter and Sphaceloma fawcettii Jenk. were evaluated using a growth rate
      method, and the active ingredient was isolated by activity-directed isolation and
      identified by determination and analysis of IR, (1)H NMR, (13)C NMR and mass
      spectra and correlative physical constants. RESULTS: The results showed that the
      extracts from stems and leaves of M. bontioides exhibited inhibitory activity
      against the seven fungi, with > 58% inhibition at 10 g L(-1) after 72 h. The
      active compound was isolated and identified as (-)-epingaione, and showed
      inhibitory activity against the above seven fungi. The inhibitory activity
      against P. mangiferae was the highest, with an EC(50) value of 77 mg L(-1). The
      EC(50) values against the other six fungi were 147-245 mg L(-1). (-)-Epingaione
      also inhibited spore germination of F. oxysporum f. sp. niveum, T. paradoxa and
      S. fawcettii. CONCLUSION: (-)-Epingaione demonstrated broad-spectrum inhibitory
      activity against plant pathogenic fungi and is promising for exploitation as a
      fungicide.

PMID- 18069658
TI  - Inheritance of beta-cypermethrin resistance in the housefly Musca domestica
      (Diptera: Muscidae).
AB  - BACKGROUND: Beta-cypermethrin, a synthetic pyrethroid insecticide, was applied
      frequently in the control of health pests including houseflies, Musca domestica
      L., in China. However, different levels of resistance to beta-cypermethrin were
      monitored in field strains of houseflies. A strain of M. domestica, 4420-fold
      resistant to beta-cypermethrin after continuous 25 generations of selection, was
      used in this paper to determine the mode of inheritance of pyrethroid resistance.
      RESULTS: The estimated realized heritability (h(2)) of beta-cypermethrin
      resistance was 0.30 in this resistant strain. Results of bioassays showed no
      significant difference in values of LD(50) and slope of log dose-probit lines
      between reciprocal progenies F(1) and F'(1), and yielded values of - 0.10 (F(1))
      and - 0.11 (F'(1)) for the degree of dominance (D). Chi-square analysis from
      responses of self-bred and backcross progenies (F(2), BC(1) and BC(2)
      respectively) indicated that the null hypothesis, a single gene responsible for
      resistance, was accepted. The minimum number of independent segregation genes was
      0.93 for F(1) by Lande's method. CONCLUSION: It was concluded that beta
      cypermethrin resistance in the housefly was inherited as a single, major,
      autosomal and incompletely recessive factor. These results would provide the
      basic information for pest management programmes.

PMID- 18069659
TI  - Herbicides, glyphosate resistance and acute mammalian toxicity: simulating an
      environmental effect of glyphosate-resistant weeds in the USA.
AB  - BACKGROUND: With the emergence of glyphosate-resistant (GR) weeds, the
      environmental consequences of alternatives to GR technology are of increasing
      importance. A well-known acute mammalian toxicity measure, the LD(50) dose for
      rats, is used to assess one potential environmental impact of the loss of GR
      technology. A new dataset with this index is used to estimate and simulate the
      effects for corn, soybeans and cotton. RESULTS: With conventional tillage it is
      found that the use of GR seeds reduces the number of LD(50) doses applied per
      hectare by 17-98% depending on crop. With no-till, the use of GR seeds reduces
      LD(50) doses only in corn. If farmers switch to conventional seeds because of GR
      weeds but maintain the same tillage practice, the present simulations suggest
      that LD(50) doses could increase by as much as 100 LD(50) doses per hectare in
      soybeans, and 500 LD(50) doses per hectare in cotton, or 11.4 and 19.8%
      respectively. CONCLUSIONS: This is the first study to use field-level data to
      assess GR technology with a mammalian toxicity environmental indicator. It has
      been found that GR crops have a positive environmental effect, and that
      alternatives to GR technology increase toxicity.

PMID- 18069660
TI  - Evidence of Notch pathway activation in the ectatic ducts of chronic
      pancreatitis.
AB  - Ductal concretions in chronic pancreatitis (CP) are one of the causes of ductal
      obstruction, resulting in pancreatic ductal hypertension (PDH) and duct ectasia.
      Ductal epithelium subjected to chronic stress by PDH may undergo molecular
      alterations, thereby not only initiating and sustaining the inflammatory process
      but also activating molecules that have transforming potential. Acino-ductal
      metaplasia and pancreatic intraepithelial neoplasia (PanIN) are frequently seen
      in CP. Using laser capture microdissection, cDNA microarrays and Ingenuity
      Pathways Analysis, we found an altered Notch pathway in the ectatic ducts of CP.
      The microarray data was further validated by real-time PCR. We also found
      elevated transcripts of Notch receptors, Notch1 and Notch3 in microdissected
      ectatic ducts of CP. The Notch pathway ligands, Jagged/Delta-like and a Notch
      target, HES-related repressor protein (HERP), were up-regulated in ectatic
      compared to normal pancreatic ducts, while another target of Notch,
      hairy/enhancer of split (HES), was down-regulated. The transcripts of Delta-like1
      and Jagged1 were increased 3.7-fold and 1.3-fold, respectively, while those of
      HERP1 were elevated 2.4-fold in the ectatic ducts of CP, compared to normal
      ducts. Immunohistochemistry showed that Jagged1 was not expressed in normal
      pancreatic ducts, while it was highly expressed in ectatic ducts. This pattern of
      Notch component alteration in ectatic ducts was mimicked to some extent in vitro
      in a human pancreatic duct epithelial (HPDE) cell line, when subjected to a
      pressure of 200 mmHg for 24 h. Therefore, we conclude that in the ectatic ducts
      of CP, PDH activates signalling pathways such as Notch, which have transforming
      potential.

PMID- 18069661
TI  - Electron localizability indicators ELI and ELIA: the case of highly correlated
      wavefunctions for the argon atom.
AB  - Electron localizability indicators based on the same-spin electron pair density
      and the opposite-spin electron pair density are studied for correlated
      wavefunctions of the argon atom. Different basis sets and reference spaces are
      used for the multireference configuration interaction method following the
      complete active space calculations aiming at the understanding of the effect of
      local electron correlation when approaching the exact wavefunction. The
      populations of the three atomic shells of Ar atom in real space are calculated
      for each case.

PMID- 18069662
TI  - Genomic gains of COL1A1-PDFGB occur in the histologic evolution of giant cell
      fibroblastoma into dermatofibrosarcoma protuberans.
AB  - Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm
      characterized by the chromosomal t(17;22), which results in the formation of the
      fusion gene COL1A1-PDGFB. This same fusion gene is also seen in the supernumerary
      ring chromosome of dermatofibrosarcoma protuberans (DFSP). Several studies have
      addressed the molecular genetics of DFSP but molecular cytogenetic
      characterization of individual areas and cell components in pure GCF and GCF/DFSP
      hybrids have not been performed. Herein, we studied the frequency and genomic
      copy number of COL1A1-PDGFB in pure GCF and GCF/DFSP hybrids, and identified the
      molecular cytogenetic signatures in individual cells in each component. Four pure
      GCF and nine GCF/DFSP hybrids were studied. All tumors exhibited classical
      histological features and CD34 expression. COL1A1 and PDGFB rearrangements were
      evaluated by fluorescence in situ hybridization (FISH) using probes for COL1A1
      and PDGFB on paraffin-embedded thin tissue sections. All GCF and GCF/DFSP hybrids
      showed unbalanced rearrangements of COL1A1-PDGFB at the molecular cytogenetic
      level. Genomic gains of COL1A1-PDGFB were found predominantly in the DFSP
      component of GCF/DFSP hybrids but in none of the pure GCF, suggesting that these
      gains are associated with the histologic evolution of GCF into DFSP. The
      molecular cytogenetic abnormalities were found not only in the spindle/stellated
      cells but also in individual nuclei of the multinucleated giant cells, suggesting
      that these cells may result from the fusion of individual neoplastic cells.

PMID- 18069664
TI  - Computational protein design: software implementation, parameter optimization,
      and performance of a simple model.
AB  - Computational protein design will continue to improve as new implementations and
      parameterizations are explored. An automated protein design procedure is
      implemented and applied to the full redesign of 16 globular proteins. We combine
      established but simple ingredients: a molecular mechanics description of the
      protein where nonpolar hydrogens are implicit, a simple solvent model, a folded
      state where the backbone is fixed, and a tripeptide model of the unfolded state.
      Sequences are selected to optimize the folding free energy, using a simple
      heuristic algorithm to explore sequence and conformational space. We show that a
      balanced parametrization, obtained here and in our previous work, makes this
      procedure effective, despite the simplicity of the ingredients. Calculations were
      done using our Proteins @ Home distributed computing platform, with the help of
      several thousand volunteers. We describe the software implementation, the
      optimization of selected terms in the energy function, and the performance of the
      method. We allowed all amino acids to mutate except glycines, prolines, and
      cysteines. For 15 of the 16 test proteins, the scores of the computed sequences
      were comparable to those of natural homologues. Using the low energy computed
      sequences in a BLAST search of the SWISSPROT database, we could retrieve natural
      sequences for all protein families considered, with no high-ranking false
      positives. The good stability of the designed sequences was supported by
      molecular dynamics simulations of selected sequences, which gave structures close
      to the experimental native structure.

PMID- 18069663
TI  - Analysis of the DND1 gene in men with sporadic and familial testicular germ cell
      tumors.
AB  - A base substitution in the mouse Dnd1 gene resulting in a truncated Dnd protein
      has been shown to be responsible for germ cell loss and the development of
      testicular germ cell tumors (TGCT) in the 129 strain of mice. We investigated the
      human orthologue of this gene in 263 patients (165 with a family history of TGCT
      and 98 without) and found a rare heterozygous variant, p. Glu86Ala, in a single
      case. This variant was not present in control chromosomes (0/4,132). Analysis of
      the variant in an additional 842 index TGCT cases (269 with a family history of
      TGCT and 573 without) did not reveal any additional instances. The variant, p.
      Glu86Ala, is within a known functional domain of DND1 and is highly conserved
      through evolution. Although the variant may be a rare polymorphism, a change at
      such a highly conserved residue is characteristic of a disease-causing variant.
      Whether it is disease-causing or not, mutations in DND1 make, at most, a very
      small contribution to TGCT susceptibility in adults and adolescents.

PMID- 18069665
TI  - An intramolecular induction correction model of the molecular dipole moment.
AB  - A model for intramolecular polarization is presented. It is used to describe the
      changes in the molecular charge distribution occurring as a response to changes
      of dihedral angles in the molecule. The model is based on a multicenter multipole
      distribution of the molecular charge distribution. The electric field from this
      charge distribution induce dipole moments in the same molecule. The model
      contains atom type parameters to describe the damping of the electric field. A
      total of four atom types are used. The parameters are fitted to a calibration set
      with various functional groups, and tested against a validation set. The error
      obtained for the calibration set is reduced by 92% and by 88% for the validation
      set, if compared to an accurate state-of-the-art force field. It is shown that
      rotating the non-polarizable multicenter multipole distribution for the
      equilibrium geometry gives too large dipole moments for dihedral angles deviating
      from the equilibrium geometry. This will lead to too large long-range attractions
      in simulations. This problem is overcome by using the dipole polarizability
      correction suggested here, which gives dipole moments very close to the Hartree
      Fock dipole moments obtained from reference calculations.

PMID- 18069666
TI  - Telomerase activity is a biomarker for high grade malignant peripheral nerve
      sheath tumors in neurofibromatosis type 1 individuals.
AB  - Telomerase activity (TA) and the expression of its enzymatic subunits, which have
      been demonstrated in many tumors, remain poorly investigated in tumors associated
      with neurofibromatosis type 1 (NF1). In this study, we analysed the association
      of TA and the expression of telomerase RNA (TR) and telomerase reverse
      transcriptase (TERT) in 23 malignant peripheral nerve sheath tumors (MPNST) (17
      high grade and 6 low grade tumors), 11 plexiform neurofibromas (PNF) and 6 dermal
      neurofibromas (DNF). TA was studied using telomerase repeat amplification
      protocol (TRAP) assay and expression of TR and TERT was investigated using
      reverse transcription PCR (RT-PCR) and real-time PCR. TA was detected in 14 out
      of 17 (82%) high grade MPNST, whereas all 6 low grade MPNST and 17 benign tumors
      were telomerase negative. The TERT transcripts were detected in all high grade
      MPNST, 50% of the low grade MPNST, and 4 benign tumors. However, the expression
      level of the TERT strikingly correlated with TA and high grade MPNST. Thus, while
      TERT expression was similar in both low grade MPNST and PNF (P = 0.115), it was
      significantly higher in high grade MPNST when compared to either low grade MPNST
      (P = 0.042), PNF (P = 0.001) or DNF tumors (P = 0.010). These findings indicate
      that TA and expression level of TERT are potential markers for high grade
      malignancy in NF1 patients.

PMID- 18069667
TI  - Electrophysiological signs and the prevalence of adverse effects of
      acetylcholinesterase inhibitors in patients with myasthenia gravis.
AB  - The aim of this prospective study was to assess whether extra discharges (EDs),
      sometimes following the compound muscle action potential, could be used as a
      neurophysiological indicator of overdose of acetylcholinesterase inhibitors
      (AChEIs) in patients with myasthenia gravis (MG). The characteristics and
      frequency of EDs were explored and the correlation of EDs with cholinergic side
      effects was also determined. Twenty-two MG patients (14 women, 8 men; 61 +/- 16
      years of age) with daily AChEI treatment were examined. The mean disease duration
      was 10 years (range 2-62 years) and all patients had been treated with AChEI
      since MG onset. Both single and repetitive stimulation of the ulnar and accessory
      nerves were performed before and 60 min after oral pyridostigmine bromide (PB)
      administration and after additional edrophonium injection. Fatigue, side effects,
      and AChE activity in blood were assessed before and 60 min after PB intake. The
      daily dose of PB ranged from 150 to 900 mg/day. Fourteen patients (64%)
      experienced daily cholinergic adverse effects, and muscarinic side effects
      correlated with AChE activity. Eleven patients (50%) developed EDs after oral PB.
      Among the eight patients with daily nicotinic side effects, EDs were
      significantly (P < 0.05) more common. Additionally, older patients were more
      prone to develop cholinergic side effects and EDs. Thus, when EDs are found,
      patients should be asked about daily muscular symptoms, which may be related to
      AChEI treatment and not solely to MG.

PMID- 18069668
TI  - Automated recognition system to classify subcellular protein localizations in
      images of different cell lines acquired by different imaging systems.
AB  - Systemic analysis of subcellular protein localization (location proteomics)
      provides clues for understanding gene functions and physiological condition of
      the cells. However, recognition of cell images of subcellular structures highly
      depends on experience and becomes the rate-limiting step when classifying
      subcellular protein localization. Several research groups have extracted specific
      numerical features for the recognition of subcellular protein localization, but
      these recognition systems are restricted to images of single particular cell line
      acquired by one specific imaging system and not applied to recognize a range of
      cell image sources. In this study, we establish a single system for automated
      subcellular structure recognition to identify cell images from various sources.
      Two different sources of cell images, 317 Vero (http://gfp-cdna.embl.de) and 875
      CHO cell images of subcellular structures, were used to train and test the
      system. When the system was trained by a single source of images, the recognition
      rate is high and specific to the trained source. The system trained by the CHO
      cell images gave high average recognition accuracy for CHO cells of 96%, but this
      was reduced to 46% with Vero images. When we trained the system using a mixture
      of CHO and Vero cell images, an average accuracy of recognition reached 86.6% for
      both CHO and Vero cell images. The system can reject images with low confidence
      and identify the cell images correctly recognized to avoid manual reconfirmation.
      In summary, we have established a single system that can recognize subcellular
      protein localizations from two different sources for location-proteomic studies.
      studies.

PMID- 18069669
TI  - Myelin-phagocytosing macrophages in isolated sciatic and optic nerves reveal a
      unique reactive phenotype.
AB  - Macrophages are key effectors in demyelinating diseases of the central and
      peripheral nervous system by phagocytosing myelin and releasing immunoregulatory
      mediators. Here, we report on a distinct, a priori anti-inflammatory reaction of
      macrophages phagocytosing myelin upon contact with damaged nerve tissue.
      Macrophages rapidly invaded peripheral (sciatic) and central (optic) nerve
      tissues in vitro, readily incorporated myelin and expressed high levels of
      phagocytosis-associated molecules (e.g., Fc and scavenger receptors). In
      contrast, factors involved in antigen presentation (MHC class-II, CD80, CD86)
      revealed only a restricted expression. In parallel, a highly ordered appearance
      of cytokines and chemokines was detected. IL-10, IL-6, CCL22, and CXCL1 were
      immediately but transiently induced, whereas CCL2, CCL11, and TGFbeta revealed
      more persisting levels. Such a profile would attract neutrophils,
      monocytes/macrophages, and Th2 cells as well as bias for a Th2-supporting
      environment. Importantly, proinflammatory/Th1-supporting factors, such as
      TNFalpha, IL-12p70, CCL3, and CCL5, were not induced. Still the simultaneous
      presence of TGFbeta and IL-6 could assist Th17 development, further depending on
      yet not present IL-23. The release pattern was clearly distinct from reactive
      phenotypes induced in isolated macrophages and microglia upon treatment with IL
      4, IL-13, bacterial lipopolysaccharide, IFNgamma, or purified myelin. Nerve
      exposed macrophages thus commit to a unique functional orientation.

PMID- 18069670
TI  - Differential regulation of trophic and proinflammatory microglial effectors is
      dependent on severity of neuronal injury.
AB  - Microglial activation has been reported to promote neurotoxicity and also
      neuroprotective effects. A possible contributor to this dichotomy of responses
      may be the degree to which proximal neurons are injured. The aim of this study
      was to determine whether varying the severity of neuronal injury influenced
      whether microglia were neuroprotective or neurotoxic. We exposed cortical
      neuronal cultures to varying degrees of hypoxia thereby generating mild (<20%
      death, 30 min hypoxia), moderate (40-60% death, 2 h hypoxia), or severe (>70%
      death, 6 h hypoxia) injuries. Twenty-four hours after hypoxia, the media from the
      neuronal cultures was collected and incubated with primary microglial cultures
      for 24 h. Results showed that the classic microglial proinflammatory mediators
      including inducible nitric oxide synthase, tumor necrosis factor alpha, and
      interleukin-1-beta were upregulated only in response to mild neuronal injuries,
      while the trophic microglial effectors brain-derived neurotrophic factor and
      glial cell line-derived neurotrophic factor were upregulated in response to all
      degrees of neuronal injury. Microglia stimulated with media from damaged neurons
      were co-cultured with hypoxic neurons. Microglia stimulated by moderate, but not
      mild or severe damage were neuroprotective in these co-cultures. We also showed
      that the severity-dependent phenomenon was not related to autocrine microglial
      signaling and was dependent on the neurotransmitters released by neurons after
      injury, namely glutamate and adenosine 5'-triphosphate. Together our results show
      that severity of neuronal injury is an important factor in determining microglial
      release of "toxic" versus "protective" effectors and the resulting neurotoxicity
      versus neuroprotection.

PMID- 18069671
TI  - A multicenter retrospective study defining the clinical and hematological
      manifestations of brucellosis and pancytopenia in a large series: Hematological
      malignancies, the unusual cause of pancytopenia in patients with brucellosis.
AB  - The aim of the study is to review the clinical manifestations and the
      hematological findings of brucellosis and pancytopenia, with or without
      hematological malignancies. The records of 202 patients with brucellosis were
      evaluated retrospectively. Among these cases of brucellosis seen in a 6 year
      period between April 1999 and June 2005, 30 patients with pancytopenia were
      identified. The most common manifestation was fever, followed by weight loss,
      anorexia, malaise, arthralgia, and hepatosplenomegaly. Bone marrow biopsies
      revealed hypercellularity or normocellularity. The most common findings in the
      bone marrow evaluation were histiocytic hemophagocytosis and granulomas. Among
      all cases, we diagnosed 5 hematological malignancies (1 acute myelogenous
      leukemia, 2 acute lymphoblastic leukemia, and 2 multiple myeloma) concurrently
      with brucellosis. The clinical symptoms and findings were similar in patients
      with and without malignancies. In cases with malignancies, the bone marrow biopsy
      revealed predominant primary disease involvement. Significant increases in ESR
      and CRP, severe anemia and thrombocytopenia were observed in patients with
      malignancies. Peripheral blood counts in patients without malignancies returned
      to normal after antibiotic treatment for brucellosis. However, pancytopenia in
      two patients with malignancies did not recover because of primary resistant
      disease. We conclude that while histiocytic hemophagocytosis may be considered as
      a major cause of pancytopenia, leukemic infiltration can also be an extreme and
      unusual cause of pancytopenia in patients in whom brucellosis was concurrently
      diagnosed with hematological malignancies.

PMID- 18069672
TI  - Survival in Danish patients with breast cancer and inflammatory bowel disease: a
      nationwide cohort study.
AB  - BACKGROUND: Incidences of inflammatory bowel disease (IBD) and of breast cancer
      have increased over the last decades. The influence of IBD on breast cancer
      prognosis, however, is unknown. We therefore examined the impact of IBD on
      treatment receipt and survival in breast cancer patients. METHODS: Information on
      breast cancer patients (stage and treatment) diagnosed between 1980 and 2004 was
      sourced from the Danish Cancer Registry. Data on IBD and potential confounders
      were extracted from the Danish National Registry of Patients covering all Danish
      hospitals. Cox regression was used to compute mortality rate ratios (MRRs) among
      breast cancer patients with IBD, compared to their non-IBD counterparts,
      adjusting for age, stage, comorbidity measured by the Charlson Index, and
      calendar year. RESULTS: We identified 71,148 breast cancer cases; 67 also had
      Crohn's disease (CD) and 216 had ulcerative colitis (UC). Patients with CD had
      more advanced stage and received radiotherapy less, and chemotherapy more,
      frequently than patients without IBD. In the adjusted analyses there was no
      substantial survival difference in breast cancer patients with and without IBD
      (MRR(CD) = 1.22; 95% confidence interval [CI] = 0.85-1.75; MRR(UC) = 1.09; 95% CI
      = 0.86-1.38). In a stratified analysis, chemotherapy was associated with poorer
      survival in patients with CD (MRR(CD) = 1.93; 95% CI = 1.00-3.72). CONCLUSIONS:
      Breast cancer patients with UC receive the same treatment and have similar
      survival to breast cancer without IBD. In contrast, breast cancer patients with
      CD are treated with radiotherapy less often. Survival of breast cancer in
      patients with CD treated with chemotherapy is poorer compared to survival in
      patients without IBD.

PMID- 18069673
TI  - Prevalence of chronic granulomatous disease in pediatric patients diagnosed with
      Crohn's disease.

PMID- 18069674
TI  - Infliximab dependency in pediatric Crohn's disease: long-term follow-up of an
      unselected cohort.
AB  - BACKGROUND: Infliximab is effective for induction and maintenance of remission in
      Crohn's disease. It is unknown how long patients should be kept on infliximab
      therapy. The primary aim of this study was to assess duration of effective
      maintenance therapy and infliximab dependency in pediatric CD patients initially
      responding to infliximab therapy. METHODS: All pediatric patients treated with
      infliximab by pediatric gastroenterologists in the Netherlands because of severe
      luminal or fistulizing CD with initial response to infliximab therapy were
      reviewed. Duration of therapy, clinical response and adverse events were
      recorded. RESULTS: Sixty-six CD patients (37 boys) in 10 hospitals were initially
      responding to infliximab therapy. Mean age at the start of infliximab therapy was
      14.5 years (range, 8.1-18.5 years). Mean follow-up since infliximab was started
      was 41.3 months (range 12-165). In total, 991 infusions were administered.
      Analysis demonstrates that 15.2% of patients had prolonged response, while 56.1%
      were infliximab dependent and 28.8% lost response. In total, 10 patients (15.2%)
      developed an infection during infliximab therapy and 8 (12.1%) had an immediate
      allergic reaction. CONCLUSIONS: Good clinical response to maintenance infliximab
      therapy was seen in 70% of patients. Infliximab maintenance therapy seems very
      effective and safe in pediatric CD. However, more than half of the patients in
      this cohort is dependent on repeated infliximab infusions. The number of
      infliximab infusions received when patients lost response to infliximab was
      diverse. There was no statistical difference regarding response to infliximab
      therapy when started early as compared to later in the course of Crohn's disease.

PMID- 18069675
TI  - Autoantibodies against ubiquitination factor E4A (UBE4A) are associated with
      severity of Crohn's disease.
AB  - BACKGROUND: Identification of a disease- and organ-specific autoantigen can
      potentially contribute to understanding molecular mechanisms involved in Crohn's
      disease (CD) and lead to development of clinically useful markers. The aim was to
      identify potential intestinal autoantigens specific to patients with CD and
      evaluate their diagnostic value. METHODS: A cDNA expression library from normal
      terminal ileum was created and screened with pooled sera from 3 randomly selected
      patients with CD. For evaluation of the diagnostic value of antibody screening,
      serum samples obtained from 39 patients with CD, 28 patients with ulcerative
      colitis (UC), and 60 healthy controls were examined for IgG against the strongest
      clone. RESULTS: We identified an intestinal cDNA clone encoding ubiquitination
      factor E4A (UBE4A), a U-box-type ubiquitin-protein ligase. The prevalence of anti
      UBE4A IgG in patients with CD was significantly higher than that in patients with
      UC or healthy controls (46.2% versus respectively 7.1%, P = 0.0006; 3.3%, P <
      0.0001). Anti-UBE4A-positive patients with CD were more likely to require surgery
      (P = 0.0013). The level of anti-UBE4A IgG was correlated with disease activity (r
      = 0.777, P < 0.0001) and associated with stricturing or penetrating disease (P =
      0.0028). Immunohistochemical studies showed upregulation of UBE4A in
      enteroendocrine cells of inflamed ileal mucosa with CD. CONCLUSIONS: Anti-UBE4A
      antibodies are potentially useful markers for detection and prediction of
      clinical activity and outcome in patients with CD.

PMID- 18069676
TI  - Morbid obesity, cardiac disease, and bariatric surgery.

PMID- 18069677
TI  - Development and validation of a noninvasive method to estimate cardiac output
      using cuff sphygmomanometry.
AB  - BACKGROUND: Obtaining cardiac output (CO) measurements noninvasively during
      routine blood pressure recording can improve hypertension management. A new
      method has been developed that estimates cardiac output using pulse-waveform
      analysis (PWA) from a brachial cuff sphygmomanometer. This study evaluates the
      ability of PWA to track changes in CO as derived by Doppler ultrasound during
      dobutamine stimulation. HYPOTHESIS: This study aims to validate the PWA CO
      estimation over a wide CO range as would be obtained by dobutamine stimulation
      during Doppler ultrasound evaluation. METHOD: A total of 48 patients undergoing
      standard dobutamine stress echocardiography testing for accepted clinical
      indications were enrolled. Among them, 44 patients (age 36-83, 18 females, 26
      males) with good waveform data for analyses provided estimates of CO in this
      study. Noninvasive measurements of CO were performed using both Doppler
      ultrasound recordings and PWA techniques simultaneously at each stage of
      dobutamine infusion. RESULTS: A total of 207 simultaneous pulse-waveform analyses
      and Doppler measurements were taken during dobutamine stress on 44 cardiac
      patients. Linear regression analysis revealed good intra-patient correlation
      between pulse-waveform analysis and Doppler at different dobutamine-induced CO
      with coefficients from r = 0.69 to 0.98 (p < 0.05). Analysis of all patients
      yielded an overall correlation of r = 0.82 (p < 0.001, bias = 0.4 L/min, standard
      deviation = 1.8 L/min). CONCLUSION: The CO measured noninvasively from a
      sphygmomanometer using this PWA method correlates well with those of Doppler
      through a range of dobutamine-stimulated levels. The CO by PWA should be useful
      for monitoring hemodynamic changes in hypertensive and cardiac patients during
      routine blood pressure measurement.

PMID- 18069678
TI  - Paradoxical septal motion after cardiac surgery: a review of 3,292 cases.
AB  - BACKGROUND: Paradoxical septal motion (PSM) is the systolic movement of the
      interventricular septum toward the right ventricle despite normal thickening. The
      PSM is a frequent echocardiographic finding after cardiac surgery. Although it is
      universally recognized, there has been no large-scale study to correlate PSM with
      the type of surgical procedure. The cause of PSM is unknown; prevailing theories
      include: (1) operation on the heart alters the degree to which it is restrained
      by the pericardium and the chest wall and (2) transient ischemia alters septal
      motion. HYPOTHESIS: The PSM is related to type of surgery and surgical approach.
      METHODS: Between 1996 and 2002, 3,292 patients underwent a first cardiac
      operation and had a postoperative echocardiogram; 313 were excluded due to other
      explanations for PSM (severe tricuspid regurgitation [TR] cardiac pacing),
      leaving a study group of 2,979 patients. Univariate and multivariate analyses
      were performed to determine which surgical characteristics were correlated with
      postoperative PSM. Septal thickening was assessed in a subset. RESULTS: On
      multivariate analysis, aortic (p = 0.02) and mitral valve surgery (p < 0.001) and
      longer cardiopulmonary bypass time (p < 0.001) were independently associated with
      PSM. Coronary artery bypass grafting (CABG) was less likely to cause PSM than non
      CABG surgery (p = 0.003) and off-pump coronary artery bypass (OPCAB) caused less
      PSM than did on-pump CABG. CONCLUSIONS: 1. Valve surgery is more likely to cause
      PSM than CABG. 2. Among patients with CABG, OPCAB causes less PSM. 3.
      Cardiopulmonary bypass time is associated with the development of PSM. 4. The
      cause of PSM is likely to be multifactorial.

PMID- 18069679
TI  - Risk of cerebrovascular accident after a first diagnosis of atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia and a major
      risk factor for cerebrovascular accident, including ischemic stroke and transient
      ischemic attack. HYPOTHESIS: Ischemic cerebrovascular accident is associated with
      increasing age and cardiovascular and cerebrovascular disease in primary care
      patients with atrial fibrillation. METHODS: Using the U.K. General Practice
      Research Database, we identified patients with chronic atrial fibrillation who
      were alive 1 month after initial diagnosis (n = 906). Potential cases of
      cerebrovascular accident were identified and confirmed by the primary care
      physician. The incidence of cerebrovascular accident was calculated. A nested
      case-control analysis was performed to identify factors associated with
      cerebrovascular accident among patients with chronic atrial fibrillation.
      RESULTS: During a mean follow-up period of 1.8 years (range: 0-3.9 years), 60
      patients with atrial fibrillation were diagnosed with a new cerebrovascular
      accident (22 cases with transient ischemic attack and 38 with ischemic stroke).
      The incidence of new cerebrovascular accident was 3.6 per 100 patient-years (95%
      confidence interval [CI]: 2.8-4.6). Increased age (odds ratios [OR] compared with
      age 40-69 years: 3.5 [95% CI: 1.2-10.5] for age 70-79 years and 4.9 [95% CI: 1.6
      15.0] for age > or = 80 years), prior cerebrovascular event (OR: 3.4; 95% CI: 1.9
      6.1) and diabetes (OR: 2.2; 95% CI: 1.0-4.9) were identified as risk factors for
      a new cerebrovascular accident. CONCLUSIONS: Among patients with atrial
      fibrillation, risk factors for a new ischemic cerebrovascular accident include
      previous ischemic stroke or transient ischemic attack, comorbid diabetes, and
      increasing age.

PMID- 18069680
TI  - David G. Harrison.

PMID- 18069681
TI  - Decision making in Parkinson's disease: Analysis of behavioral and physiological
      patterns in the Iowa gambling task.
AB  - Recent studies suggest that social recognition processes are affected by
      Parkinson's disease (PD). However, whether PD patients exhibit behavioral changes
      is still controversial. The purpose of the present study was to examine the
      decision making of PD patients performing the Iowa Gambling Task (IGT). We
      recruited a large number of early, nondemented PD patients for the IGT. We also
      recorded the skin conductance responses (SCRs) during the task as a measure of
      emotional arousal. Compared with the normal control (NC) subjects, PD patients
      selected more disadvantageous decks in the IGT, and their SCRs were lower than
      those of NC subjects before making decisions and after receiving reward or
      punishment. The tendency toward risky choices was not correlated with age,
      education, global cognitive function, or the severity of the disease. These
      results confirmed that the decision making of PD patients was affected by the
      disease, rather than by other cognitive functions; moreover, such behavior was
      related to lower emotional responses. Behavioral and SCR patterns of PD patients
      were similar to those of amygdala-damaged patients. The response bias toward
      risky choices in PD may be explained by the dysfunction of the amygdala, which is
      known to be involved in risk evaluation.

PMID- 18069682
TI  - Ascites in tropical endomyocardial fibrosis.

PMID- 18069685
TI  - DFT conformational studies of alpha-maltotriose.
AB  - Recent DFT optimization studies on alpha-maltose improved our understanding of
      the preferred conformations of alpha-maltose. The present study extends these
      studies to alpha-maltotriose with three alpha-D-glucopyranose residues linked by
      two alpha-[1-->4] bridges, denoted herein as DP-3's. Combinations of gg, gt, and
      tg hydroxymethyl groups are included for both "c" and "r" hydroxyl rotamers. When
      the hydroxymethyl groups are for example, gg-gg-gg, and the hydroxyl groups are
      rotated from all clockwise, "c", to all counterclockwise, "r", the minimum energy
      positions of the bridging dihedral angles (phi(H) and psi(H)) move from the
      region of conformational space of (-, -), relative to (0 degrees , 0 degrees), to
      a new position defined by (+, +). Further, it was found previously that the
      relative energies of alpha-maltose gg-gg-c and "r" conformations were very close
      to one another; however, the DP-3's relative energies between hydroxyl "c" or "r"
      rotamers differ by more than one kcal/mol, in favor of the "c" form, even though
      the lowest energy DP-3 conformations have glycosidic dihedral angles similar to
      those found in the alpha-maltose study. Preliminary solvation studies using
      COSMO, a dielectric solvation method, point to important solvent contributions
      that reverse the energy profiles, showing an energy preference for the "r" forms.
      Only structures in which the rings are in the chair conformation are presented
      here.

PMID- 18069686
TI  - Flavins as organocatalysts for environmentally benign molecular transformations.
AB  - Recent progress in the development of flavin-catalyzed oxidations and related
      reactions is described with respect to scope, limitation, and reaction mechanism.
      The 4a-hydroperoxyflavins, which are the most simplified model compounds of
      flavoenzymes, act as catalytically active species for the oxidation of organic
      substrates with the help of H(2)O(2) or O(2) as a mild oxidant. This principle
      behind the simulation of flavoenzymes led to the discovery of a variety of
      environmentally benign, oxidative transformations of secondary amines to
      nitrones, tertiary amines to N-oxides, sulfides to sulfoxides, and Baeyer
      Villiger oxidations of ketones. Asymmetric oxidation of sulfides can also be
      performed with several chiral flavin catalysts. One of the fortunate outcomes of
      this study is the development of an environmentally friendly ("green") method for
      the "aerobic hydrogenation" of olefins, which is achieved by in situ generation
      of diimide with the aid of the flavin-catalyzed oxidation of hydrazine under an
      O(2) atmosphere.

PMID- 18069684
TI  - Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset
      inflammatory bowel disease.
AB  - BACKGROUND: While activation of the IL-6-dependent transcription factor signal
      transducer and activator of transcription 3 (STAT3) has been implicated in the
      pathogenesis of inflammatory bowel disease (IBD), a direct effect on mucosal gene
      expression and inflammation has not been shown. We hypothesized that a
      proinflammatory IL-6:STAT3-dependent biological network would be up regulated in
      pediatric-onset IBD patients, and would be associated with the severity of
      mucosal inflammation. METHODS: Patients with pediatric-onset IBD were enrolled at
      diagnosis and during therapy. Serum cytokine analysis was performed using
      Bioplex. STAT3 phosphorylation (pSTAT3) in peripheral blood leukocytes (PBLs) was
      assessed by flow cytometry. Immunohistochemistry of colonic mucosa was used to
      localize pSTAT3 and STAT3 target genes. Microarray analysis was used to determine
      RNA expression profiles from colon biopsies. RESULTS: Circulating IL-6 was
      upregulated in active IBD patients at diagnosis and during therapy. STAT3
      activation was increased in PB granulocytes, IL-6-stimulated CD3(+)/CD4(+)
      lymphocytes, and affected colon biopsies of IBD patients. The frequency of
      pSTAT3+ PB granulocytes and colon epithelial and lamina propria cells was highly
      correlated with the degree of mucosal inflammation. Microarray and Ingenuity
      Systems bioinformatics analysis identified IL-6:STAT3-dependent biological
      networks upregulated in IBD patients which control leukocyte recruitment, HLA
      expression, angiogenesis, and tissue remodeling. CONCLUSIONS: A proinflammatory
      IL6:STAT3 biologic network is upregulated in active pediatric IBD patients at
      diagnosis and during therapy. Specific targeting of this network may be effective
      in reducing mucosal inflammation.

PMID- 18069687
TI  - HB-EGF decelerates cell proliferation synergistically with TGFalpha in perinatal
      distal lung development.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member
      of the EGF family of growth factors that is suggested to be involved in distal
      lung development. In HB-EGF null (HB(del/del)) newborns, a histopathologic
      analysis revealed abnormally thick saccular walls occurring from embryonic day
      18.5 that reduced the terminal saccular space area. HB-EGF gene deletion resulted
      in a significant increase in cell proliferation, indicating that HB-EGF
      suppresses distal lung cell proliferation. Furthermore, an analysis of saccular
      morphology and proliferation in HB-EGF and transforming growth factor-alpha
      (TGFalpha) double-mutant newborns revealed that HB-EGF and TGFalpha function
      synergistically in this suppression. Finally, crosses between HB(del/del) mice
      and waved 2 mice, a hypomorphic EGF receptor (EGFR) mutant strain, suggest that
      HB-EGF and EGFR cooperate in this process. Thus, HB-EGF has a novel suppressive
      function that contributes to decelerating distal lung cell proliferation
      synergistically with TGFalpha through EGFR in perinatal distal lung development.

PMID- 18069688
TI  - Regulation of the Drosophila lin-41 homologue dappled by let-7 reveals
      conservation of a regulatory mechanism within the LIN-41 subclade.
AB  - Drosophila Dappled (DPLD) is a member of the RBCC/TRIM superfamily, a protein
      family involved in numerous diverse processes such as developmental timing and
      asymmetric cell divisions. DPLD belongs to the LIN-41 subclade, several members
      of which are micro RNA (miRNA) regulated. We re-examined the LIN-41 subclade
      members and their relation to other RBCC/TRIMs and dpld paralogs, and identified
      a new Drosophila muscle specific RBCC/TRIM: Another B-Box Affiliate, ABBA. In
      silico predictions of candidate miRNA regulators of dpld identified let-7 as the
      strongest candidate. Overexpression of dpld led to abnormal eye development,
      indicating that strict regulation of dpld mRNA levels is crucial for normal eye
      development. This phenotype was sensitive to let-7 dosage, suggesting let-7
      regulation of dpld in the eye disc. A cell-based assay verified let-7 miRNA down
      regulation of dpld expression by means of its 3'-untranslated region. Thus, dpld
      seems also to be miRNA regulated, suggesting that miRNAs represent an ancient
      mechanism of LIN-41 regulation.

PMID- 18069689
TI  - Patterning the embryonic kidney: BMP signaling mediates the differentiation of
      the pronephric tubules and duct in Xenopus laevis.
AB  - The Bone morphogenetic proteins (BMPs) mediate a wide range of diverse cellular
      behaviors throughout development. Previous studies implicated an important role
      for BMP signaling during the differentiation of the definitive mammalian kidney,
      the metanephros. In order to examine whether BMP signaling also plays an
      important role during the patterning of earlier renal systems, we examined the
      development of the earliest nephric system, the pronephros. Using the amphibian
      model system Xenopus laevis, in combination with reagents designed to inhibit BMP
      signaling during specific stages of nephric development, we revealed an
      evolutionarily conserved role for this signaling pathway during renal
      morphogenesis. Our results demonstrate that conditional BMP inhibition after
      specification of the pronephric anlagen is completed, but prior to the onset of
      morphogenesis and differentiation of renal tissues, results in the severe
      malformation of both the pronephric duct and tubules. Importantly, the effects of
      BMP signaling on the developing nephron during this developmental window are
      specific, only affecting the developing duct and tubules, but not the glomus.
      These data, combined with previous studies examining metanephric development in
      mice, provide further support that BMP functions to mediate morphogenesis of the
      specified renal field during vertebrate embryogenesis. Specifically, BMP
      signaling is required for the differentiation of two types of nephric structures,
      the pronephric tubules and duct.

PMID- 18069690
TI  - SMAD expression in the testis: an insight into BMP regulation of spermatogenesis.
AB  - Bone morphogenetic proteins (BMPs), members of the transforming growth factor
      beta superfamily, extensively influence events that establish male fertility,
      affecting germ cells and somatic cells throughout fetal and postnatal life. BMP
      signals are relayed by SMAD proteins, transcription factors that translocate to
      the nucleus upon ligand stimulation. We show that BMP signaling in the testis may
      be regulated by selective expression of BMP-responsive and inhibitory SMADs, with
      expression differing between the first wave and adult spermatogenesis. Smad1,
      Smad5, Smad8, Smad4, Smad6, and Smad7 expression is ubiquitous during testis
      development but becomes cell-specific in the adult. Furthermore, regulated SMAD6
      protein expression at the onset of spermatogenesis suggests differential
      responsiveness of spermatogonial subpopulations to ligands. In vitro, immature
      Sertoli cells and spermatogonia transduce BMP2 and BMP4 signals by means of
      SMAD1, SMAD5, and SMAD8. Based on these findings, we extrapolate these data to
      interpret BMP mutant testis phenotypes in terms of SMAD availability for signal
      transduction.

PMID- 18069691
TI  - Multicellular rosette formation during cell ingression in the avian primitive
      streak.
AB  - Cell movements are a fundamental feature during the development of multi-cellular
      organisms. In amniote gastrulation, cells ingress through the primitive streak,
      which identifies the anterior-posterior axis of the embryo. We investigated the
      cytoskeletal architecture during these morphogenetic processes and characterized
      microtubule organisation in whole chick embryos. This revealed the distribution
      of cells with polarized and radial microtubule (MT) arrays across different
      regions of the embryo. Cells in the epiblast usually displayed radial MT-arrays,
      while the majority of cells in the primitive streak had polarized MT-arrays.
      Within the primitive streak, many cells organized into groups and were arranged
      in rosette-like structures with a distinct centre characterized by an
      accumulation of actin. Extended confocal microscopy and three-dimensional image
      reconstruction identified tips of polarized cells that were protruding from the
      plane of rosettes, usually from the centre. We propose that organization into
      higher order structures facilitates cell ingression during gastrulation.

PMID- 18069692
TI  - The macroPARP genes Parp-9 and Parp-14 are developmentally and differentially
      regulated in mouse tissues.
AB  - The macroPARPs Parp-9 and Parp-14 are macro domain containing poly(ADP-ribose)
      polymerases involved in transcriptional regulation in response to
      immunoregulatory cytokines. Their genes reside in the same locus (16B3), and the
      Parp-9 gene lies head-to-head and shares its promoter with the gene encoding its
      partner, Bbap. Here, we provide a detailed analysis of Parp-9, Parp-14, and Bbap
      expression during mouse development and adulthood. Parp-9 is developmentally
      regulated, and prominently expressed in the thymus and specific regions of the
      brain and gut. In adults, highest expression is maintained in the thymus and
      intestine. Parp-14 is more weakly expressed, mainly in the thymus during
      development and in adulthood. In addition, we show that Bbap is essentially
      coexpressed with Parp-9 during development and in adult mouse. However, the
      different levels of their transcripts detected in the developing brain and gut
      suggest that Bbap and Parp-9 display both common and independent tissue-specific
      regulations.

PMID- 18069693
TI  - Developmental expression of LC3alpha and beta: absence of fibronectin or
      autophagy phenotype in LC3beta knockout mice.
AB  - Murine light chain 3 (LC3) exists as two isoforms, LC3alpha and beta: LC3beta is
      an RNA-binding protein that enhances fibronectin (FN) mRNA translation, and is
      also a marker of autophagy. We report embryonic expression patterns for LC3alpha
      and LC3beta, with some overlap but notable differences in the brain, and in
      tissues of non-neuronal origin. LC3beta knockout (-/-) mice develop normally
      without a compensatory increase in LC3alpha. LC3beta-/- embryonic fibroblasts
      (MEFs) exhibit reduced FN synthesis but maintain wild type (WT) levels of FN
      protein. No significant changes in proteins associated with FN turnover, i.e.,
      caveolin-1, LRP-1, or matrix metalloproteinases were identified. Autophagosomes
      form in amino acid-starved LC3beta-/-MEFs, and Caesarean-delivered pups survive
      as long as WT pups without an increase in LC3-related proteins linked to
      autophagy. These results suggest novel compensatory mechanisms for loss of
      LC3beta, ensuring proper FN accumulation and autophagy during fetal and neonatal
      life.

PMID- 18069694
TI  - Transcriptional profiling of the megabladder mouse: a unique model of bladder
      dysmorphogenesis.
AB  - Recent studies in our lab identified a mutant mouse model of obstructive
      nephropathy designated mgb for megabladder. Homozygotic mgb mice (mgb-/-) develop
      lower urinary tract obstruction in utero due to a lack of bladder smooth muscle
      differentiation. This defect is the result of a random transgene
      insertion/translocation into chromosomes 11 and 16. Transcriptional profiling
      identified a significantly over-expressed cluster of gene products located on the
      translocated fragment of chromosome 16 including urotensin II-related peptide
      (Urp), which was shown to be preferentially over-expressed in developing mgb-/-
      bladders. Pathway analysis of mgb microarray data indicated dysregulation of at
      least 60 gene products associated with smooth muscle development. In conclusion,
      the results of this study indicate that the molecular pathways controlling normal
      smooth muscle development are severely altered in mgb-/- bladders, and provide
      the first evidence that Urp may play a critical role in bladder smooth muscle
      development.

PMID- 18069695
TI  - Nonalcoholic steatohepatitis in chronic hepatitis C: A new classification?

PMID- 18069696
TI  - L-tyrosine production by recombinant Escherichia coli: fermentation optimization
      and recovery.
AB  - L-tyrosine (L-tyr) overproducing Escherichia coli strain derived from an L
      phenylalanine (L-phe) overproducing strain is characterized in 10 L and 200 L
      scale fermentations. Deletion of the chromosomal region encoding for the pheA
      gene, chorismate mutase/prephenate dehydratase, its leader peptide (pheL) and its
      associated promoter resulted in significant increase in L-tyr production (Olson
      et al., 2007. Appl Microbiol Biotechnol 74(5):1031-1040). Further increase in
      titer was achieved by overexpressing tyrA, encoding chorismate mutase/prephenate
      dehydrogenase, from a strong non-native trc promoter (Olson et al., 2007. Appl
      Microbiol Biotechnol 74(5):1031-1040). Fermentation optimization studies include
      media component selection; glucose feed optimization, antifoam agent selection,
      and understanding fermentation parameters affecting foaming. Generational
      stability of the strain was evaluated along with rate, titer, and yield of
      tyrosine formation from glucose. L-tyr titer of 55 g/L in 48 h was demonstrated
      in 200 L batches, is the highest titer published till date. We have also
      evaluated two primary separations schemes to isolate and purify L-tyr from the
      fermentation broth. Physical separation of L-tyr crystals from biomass using a
      decanter type centrifuge, based on the density difference between the solids, is
      compared and contrasted with a strategy where L-tyr is first dissolved at pH 11.5
      and then acid precipitated from clarified supernatants following removal of
      biomass using membrane filtration. L-tyr product purity of 98% with yields
      ranging from 90% to 95% is demonstrated.

PMID- 18069697
TI  - Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective
      validation of the noninvasive diagnostic criteria for hepatocellular carcinoma.
AB  - This study prospectively evaluates the accuracy of contrast-enhanced ultrasound
      (CEUS) and dynamic magnetic resonance imaging (MRI) for the diagnosis of nodules
      20 mm or smaller detected during ultrasound (US) surveillance. We included 89
      patients with cirrhosis [median age, 65 years; male 53, hepatitis C virus 68,
      Child-Pugh A 80] without prior hepatocellular carcinoma (HCC) in whom US detected
      a small solitary nodule (mean diameter, 14 mm). Hepatic MRI, CEUS, and fine
      needle biopsy (gold standard) (FNB) were performed at baseline. Non-HCC cases
      were followed (median 23 months) by CEUS/3 months and MRI/6 months. FNB was
      repeated up to 3 times and on detection of change in aspect/size. Intense
      arterial contrast uptake followed by washout in the delayed/venous phase was
      registered as conclusive for HCC. Final diagnoses were: HCC (n = 60),
      cholangiocarcinoma (n = 1), and benign lesions (regenerative/dysplastic nodule,
      hemangioma, focal nodular hyperplasia) (n = 28). Sex, cirrhosis cause, liver
      function, and alpha-fetoprotein (AFP) levels were similar between HCC and non-HCC
      groups. HCC patients were older and their nodules significantly larger (P <
      0.0001). First biopsy was positive in 42 of 60 HCC patients. Sensitivity,
      specificity, and positive and negative predictive values of conclusive profile
      were 61.7%, 96.6%, 97.4%, and 54.9%, for MRI, 51.7%, 93.1%, 93.9%, and 50.9%, for
      CEUS. Values for coincidental conclusive findings in both techniques were 33.3%,
      100%, 100%, and 42%. Thus, diagnosis of HCC 20 mm or smaller can be established
      without a positive biopsy if both CEUS and MRI are conclusive. However,
      sensitivity of these noninvasive criteria is 33% and, as occurs with biopsy,
      absence of a conclusive pattern does not rule out malignancy. These results
      validate the American Association for the Study of Liver Disease (AASLD)
      guidelines.

PMID- 18069698
TI  - Individualized treatment duration for hepatitis C genotype 1 patients: A
      randomized controlled trial.
AB  - It was hypothesized that in hepatitis C virus (HCV) genotype 1 patients, variable
      treatment duration individualized by first undetectable HCV RNA is as effective
      as standard 48-week treatment. Patients (n = 696) received peginterferon alfa-2a,
      180 mg/week, or peginterferon alfa-2b, 1.5 mg/kg/week, plus ribavirin, 1000-1200
      mg/day, for 48 weeks (standard, n = 237) or for 24, 48, or 72 weeks if HCV-RNA
      negative at weeks 4, 8, or 12, respectively (variable, n = 459). Sustained
      virologic response (SVR) was achieved in 45.1% [95% confidence interval (CI) 38.8
      51.4] of the patients in the standard group and in 48.8% (CI 44.2-53.3) of the
      patients in the variable group (P = 0.37). The percentages of patients who first
      achieved undetectable HCV RNA at weeks 4, 8, or 12 were 26.7%, 27.8%, and 11.3%,
      respectively. In the standard treatment group, 87.1%, 70.3%, and 38.1% of
      patients who first achieved undetectable HCV RNA at 4, 8, or 12 weeks attained
      SVRs, respectively. In the variable group, corresponding SVR rates were 77.2%,
      71.9%, and 63.5%. Low viremia levels and young age were independent predictors of
      response at week 4 [rapid virologic response (RVR)]. RVR patients with baseline
      viremia >or=400,000 IU/mL achieved higher SVR rates when treated for 48 weeks
      rather than 24 weeks (86.8% versus 73.1%, P = 0.14). The only predictive factor
      of SVR in RVR patients was advanced fibrosis. CONCLUSION: Variable treatment
      duration ensures SVR rates similar to those of standard treatment duration,
      sparing unnecessary side effects and costs.

PMID- 18069699
TI  - Myocardin expression during avian embryonic heart development requires the
      endoderm but is independent of BMP signaling.
AB  - Myocardin, a serum response factor cofactor, plays an important role in
      regulating heart and smooth muscle development. To investigate myocardin function
      during early stages of heart development, we isolated the chicken orthologue of
      myocardin and characterized its expression between Hamburger and Hamilton stages
      3 and 15. At stage 4, myocardin transcripts are detected in the lateral and
      extraembryonic mesoderm, become progressively localized to the precardiac
      mesoderm and the differentiated myocardium and are also seen in smooth muscle
      cells of the developing vascular plexus. Surprisingly, myocardin expression
      within the developing chicken embryo precedes that of the homeodomain
      transcription factor Nkx2.5. Embryonic dissection studies demonstrate that
      signals from the endoderm are required for myocardin expression within the
      precardiac mesoderm. However, unlike Nkx2.5, myocardin expression is not
      regulated by bone morphogenetic protein (BMP) signaling. These results suggest
      that initial expression of myocardin in the precardiac mesoderm is regulated by a
      signaling pathway that is parallel to, and independent of, Nkx2.5 expression.

PMID- 18069700
TI  - Human fetal cardiovascular profile score and neonatal outcome in intrauterine
      growth restriction.
AB  - OBJECTIVE: To determine whether low cardiovascular profile (CVP) score has
      prognostic value for predicting neonatal mortality and severe morbidity in human
      fetuses with growth restriction. METHODS: Seventy-five consecutive growth
      restricted fetuses with Doppler examination of cardiovascular hemodynamics within
      a week prior to delivery comprised the study population. Hydrops, heart size,
      cardiac function and venous and arterial hemodynamics were evaluated for CVP
      score. The primary outcome measures were neonatal mortality and cerebral palsy.
      RESULTS: During the neonatal period, six of 75 neonates died and two had cerebral
      palsy (Group 1, n = 8). Compared with the fetuses discharged home from hospital
      (Group 2, n = 67), those in Group 1 were delivered at an earlier gestational age
      (28 (range, 24-35) weeks vs. 35 (range, 26-40) weeks, P < 0.01) and had lower CVP
      scores (4 (range, 2-6) vs. 9 (range, 5-10), P < 0.0001). All CVP subscale scores
      were lower (P < 0.01) in Group 1 than in Group 2 fetuses. Gestational age
      adjusted hazard ratios (95% CIs) for adverse neonatal outcome were highest for
      cardiomegaly (13.9 (1.7-114.3), P = 0.014), monophasic atrioventricular filling
      pattern or holosystolic tricuspid regurgitation (9.5 (2.3-38.4), P = 0.002) and
      atrial pulsations in the umbilical vein 7.7 (1.4-41.2), P = 0.017). CONCLUSIONS:
      Growth-restricted fetuses with adverse neonatal outcome have lower CVP scores
      than do fetuses with favorable neonatal outcome. The strongest predictors for
      adverse neonatal outcome in the CVP score were cardiomegaly, abnormal cardiac
      function with monophasic atrioventricular filling or holosystolic tricuspid
      regurgitation and increased systemic venous pressure. These assessments have
      independent prognostic power for adverse neonatal outcome even after adjustment
      for gestational age.

PMID- 18069701
TI  - Validation of a capillary zone electrophoresis method for the comparative
      determination of etoricoxib in pharmaceutical formulations.
AB  - A CZE method was developed and validated for the analysis of etoricoxib in
      pharmaceutical dosage forms, using prilocaine as an internal standard. The CZE
      method was carried out on a fused-silica capillary (50 microm id, effective
      length 40 cm). The BGE consisted of 25 mM tris-phosphate solution at pH 2.5. The
      capillary temperature was maintained at 35 degrees C, the applied voltage was 25
      kV, the injection was performed using the pressure mode at 50 mbar for 5 s, with
      detection at 234 nm using a photodiode array detector. The method was linear in
      the range of 2-150 microg/mL (r(2) = 0.9999). The specificity and stability
      indicating capability were proven through the degradation studies and showing
      also that there was no interference of the excipients of the formulation. The
      accuracy was 99.49% with RSD of 0.66%. The limits of quantitation and detection
      were 2 and 0.58 microg/mL, respectively. Moreover, method validation demonstrated
      acceptable results for the precision, sensitivity, and robustness. The proposed
      method was successfully applied for the quantitative analysis of etoricoxib
      pharmaceutical formulations, and the results compared to the HPLC and LC-MS/MS
      methods, showing nonsignificant difference (p >0.05).

PMID- 18069702
TI  - Simultaneous determination of 15 marker constituents in various radix Astragali
      preparations by solid-phase extraction and high-performance liquid
      chromatography.
AB  - An improved quality control method was developed to simultaneously determine 15
      major constituents (eight flavonoids and seven saponins) in various radix
      Astragali preparations, using SPE for pretreatment of samples, HPLC with diode
      array and evaporative light scattering detectors (DAD-ELSD) for quantification in
      one run, and HPLC-ESI-TOF/MS for definite identification of compounds in
      preparations. Optimum separations were obtained with a ZORBAX C(18) column, using
      a gradient elution with 0.3% aqueous formic acid and ACN. This established method
      was fully validated with respect to linearity, precision, repeatability, and
      accuracy, and was successfully applied to quantify the 15 compounds in 19
      commercial samples, including 3 dosage forms, i. e., oral solution, injection,
      concentrated granule, and its processed products of radix Astragali. The results
      demonstrated that many factors might result in significant differences in quality
      of the final preparations, including crude drugs, pretreatment processes,
      manufacturing procedure, storage conditions, etc. Then the developed method
      provided a reasonable and powerful manner to ensure the efficacy, safety, and
      batch-to-batch uniformity of radix Astragali products by standardizing each
      procedure, and thus should be proposed as quality control for the clinical use
      and modernization of herbal preparations.

PMID- 18069703
TI  - Solid-phase microextraction for the determination of benzoylureas in orange juice
      using liquid chromatography combined with post-column photochemically induced
      fluorimetry derivatization and fluorescence detection.
AB  - A solid-phase microextraction (SPME) method has been developed for the
      determination of six benzoylureas (diflubenzuron, triflumuron, hexaflumuron,
      teflubenzuron, lufenuron, and flufenoxuron) in natural orange juice based on the
      direct immersion mode of a 60 microm polydimethylsiloxane/divinylbenzene fiber.
      An orange juice was obtained from blended, homogenized, and diluted ecological
      natural orange juice samples. An aliquot of 3 mL of a spiked sample was extracted
      under optimum SPME conditions. The determination of benzoylureas was carried out
      using HPLC combined with post-column photochemically induced fluorimetry
      derivatization and fluorescence detection. The limits of quantification obtained
      in matrix were within the range of 0.02 to 0.04 mg/kg and these limits are lower
      than the maximum residue levels established in Spanish regulations for all
      pesticides in this study. Recoveries in juice samples ranged between 85 and 110%
      and relative standard deviations between 1.8 and 7.4%.

PMID- 18069704
TI  - GC/MS of terpenes in walnut-tree leaves after accelerated solvent extraction.
AB  - Terpenes, e. g. (+)-alpha-pinene, (-)-camphene, (-)-(-pinene, myrcene, R-(+)
      limonene, eucalyptol, (+/-)-linalool, (-)-bornyl acetate, (-)-trans
      caryophyllene, and alpha-humulene were determined in leaves of walnut trees from
      the Juglandaceae family (walnut tree, royal (J. regia L.), black (J. nigra L.),
      and Siebold (J. sieboldiana, var. Cordiformis Lam.) using gas chromatography with
      mass spectrometric detection. Terpenes were repeatedly (3 cycles, 5 min each)
      extracted from leaves of walnut trees by accelerated (pressurized) solvent
      extraction (ASE) 150 bar and 120 degrees C. The efficiency of ASE extraction was
      superior to that of steam distillation, solvent extraction according to Soxhlet,
      sonication, and extraction by agitation. Differences in relative concentrations
      and distribution of terpenes were studied in dependence on the species of walnut
      tree and on different locations.

PMID- 18069705
TI  - Quality evaluation of Yin Chen Hao Tang extract based on fingerprint chromatogram
      and simultaneous determination of five bioactive constituents.
AB  - A completely validated method based on HPLC coupled with photodiode array
      detector (HPLC-UV) was described for evaluating and controlling quality of Yin
      Chen Hao Tang extract (YCHTE). First, HPLC-UV fingerprint chromatogram of YCHTE
      was established for preliminarily elucidating amount and chromatographic
      trajectory of chemical constituents in YCHTE. Second, for the first time, five
      mainly bioactive constituents in YCHTE were simultaneously determined based on
      fingerprint chromatogram for furthermore controlling the quality of YCHTE
      quantitatively. The developed method was applied to analyze 12 batches of YCHTE
      samples which consisted of herbal drugs from different places of production,
      showed acceptable linearity, intraday (RSD <5%), interday precision (RSD <4.80%),
      and accuracy (RSD <2.80%). As a result, fingerprint chromatogram determined 15
      representative general fingerprint peaks, and the fingerprint chromatogram
      resemblances are all better than 0.9996. The contents of five analytes in
      different batches of YCHTE samples do not indicate significant difference. So, it
      is concluded that the developed HPLC-UV method is a more fully validated and
      complete method for evaluating and controlling the quality of YCHTE.

PMID- 18069706
TI  - From storable sources of atomic Nb- and Ta- ions to isolable anionic tris(1,3
      butadiene)metal complexes: [M(eta(4)-C4H6)3]-, M = Nb, Ta.

PMID- 18069707
TI  - Palladium-catalyzed stereospecific substitution of alpha,beta-unsaturated
      gamma,delta-epoxy esters by alcohols with double inversion of configuration:
      synthesis of 4-alkoxy-5-hydroxy-2-pentenoates.

PMID- 18069709
TI  - Highly selective synthesis of C60 disks on graphite substrate by a vapor-solid
      process.

PMID- 18069708
TI  - Addition of an alpha-hydroxy acid to the genetic code of bacteria.

PMID- 18069710
TI  - Radical polymerization tracked by single molecule spectroscopy.

PMID- 18069711
TI  - Quantitatively correlating the effect of ligand-substituent size in asymmetric
      catalysis using linear free energy relationships.

PMID- 18069712
TI  - Ionic liquids and microwaves--making zeolites for emerging applications.

PMID- 18069713
TI  - Amidophosphane-copper(I)-catalyzed asymmetric conjugate addition of dialkylzinc
      reagents to racemic 6-substituted cyclohexenones to form 2,5-di- and 2,2,5
      trisubstituted cyclohexanones.
AB  - The asymmetric conjugate addition of dialkylzinc reagents to racemic 6
      substituted cyclohexenones under the catalysis of chiral amidophosphane-copper(I)
      complexes gave a mixture of nearly equal amounts of the corresponding trans- and
      cis-disubstituted cyclohexanones with extremely high catalyst-controlled
      enantioselectivity. Epimerization with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)
      led to the conversion of these mixtures into the thermodynamically more stable
      trans-2,5-disubstituted cyclohexanone as the major product with up to 96% ee in
      up to 96% yield. The regio- and stereoselective alkylation of the disubstituted
      cyclohexanone products via the thermodynamically favored enolate gave 2,2,5
      trisubstituted cyclohexanones with a quaternary asymmetric carbon atom in good
      yield.

PMID- 18069714
TI  - Accelerating and decelerating effects of metal ions on electron-transfer
      reduction of quinones as a function of temperature and binding modes of metal
      ions to semiquinone radical anions.
AB  - The accelerating effect of Sc(3+) on the electron-transfer (ET) reduction of the
      p-benzoquinone derivative 1-(p-tolylsulfinyl)-2,5-benzoquinone (TolSQ) by 10,10'
      dimethyl-9,9'-biacridine ((AcrH)(2)) at 233 K changes to a decelerating effect
      with increasing reaction temperature; the observed second-order rate constant
      k(et) decreases with increasing Sc(3+) concentration at high concentrations of
      Sc(3+) at 298 K. At 263 K the k(et) value remains constant with increasing Sc(3+)
      concentration. Such a remarkable difference with regard to dependence of k(et) on
      [Sc(3+)] between low and high temperatures results from the difference in
      relative activity of two ET pathways that depend on temperature, one of which
      affords 1:1 complex TolSQ*(-)-Sc(3+), and the other 1:2 complex TolSQ*(-)
      (Sc(3+))(2) with additional binding of Sc(3+) to TolSQ*(-)-Sc(3+). The formation
      of TolSQ*(-)-Sc(3+) and TolSQ*(-)-(Sc(3+))(2) complexes was confirmed by EPR
      spectroscopy in the ET reduction of TolSQ in the presence of low and high
      concentrations of Sc(3+), respectively. The effects of metal ions on other ET
      reactions of quinones to afford 1:1 and 1:2 complexes between semiquinone radical
      anions and metal ions are also reported. The ET pathway affording the 1:2
      complexes has smaller activation enthalpies DeltaH( not equal) and more negative
      activation entropies DeltaS( not equal) because of stronger binding of metal ions
      and more restricted geometries of the ET transition states as compared with the
      ET pathway to afford the 1:1 complexes.

PMID- 18069715
TI  - New insights into the polymerization of methyl methacrylate initiated by rare
      earth borohydride complexes: a combined experimental and computational approach.
AB  - Polymerization of methyl methacrylate (MMA) initiated by the rare-earth
      borohydride complexes [Ln(BH(4))(3)(thf)(3)] (Ln=Nd, Sm) or
      [Sm(BH(4))(Cp*)(2)(thf)] (Cp*=eta-C(5)Me(5)) proceeds at ambient temperature to
      give rather syndiotactic poly(methyl methacrylate) (PMMA) with molar masses M(n)
      higher than expected and quite broad molar mass distributions, which is
      consistent with a poor initiation efficiency. The polymerization of MMA was
      investigated by performing density functional theory (DFT) calculations on an eta
      C(5)H(5) model metallocene and showed that in the reaction of [Eu(BH(4))(Cp)(2)]
      with MMA the borate [Eu(Cp)(2){(OBH(3))(OMe)C=C(Me)(2)}] (e-2) complex, which
      forms via the enolate [Eu(Cp)(2){O(OMe)C=C(Me)(2)}] (e), is calculated to be
      exergonic and is the most likely of all of the possible products. This product is
      favored because the reaction that leads to the formation of carboxylate
      [Eu(Cp)(2){OOC-C(Me)(=CH(2))}] (f) is thermodynamically favorable, but
      kinetically disfavored, and both of the potential products from a Markovnikov
      [Eu(Cp)(2){O(OMe)C-CH(Me)(CH(2)BH(3))}] (g) or anti-Markovnikov
      [Eu(Cp)(2){O(OMe)C-C(Me(2))(BH(3))}] (h) hydroboration reaction are also
      kinetically inaccessible. Similar computational results were obtained for the
      reaction of [Eu(BH(4))(3)] and MMA with all of the products showing extra
      stabilization. The DFT calculations performed by using [Eu(Cp)(2)(H)] to model
      the mechanism previously reported for the polymerization of MMA initiated by
      [Sm(Cp*)(2)(H)](2) confirmed the favorable exergonic formation of the
      intermediate [Eu(Cp)(2){O(OMe)C=C(Me)(2)}] (e'') as the kinetic product, this
      enolate species ultimately leads to the formation of PMMA as experimentally
      observed. Replacing H by BH(4) thus prevents the 1,4-addition of the
      [Eu(BH(4))(Cp)(2)] borohydride ligand to the first incoming MMA molecule and
      instead favors the formation of the borate complex e-2. This intermediate is the
      somewhat active species in the polymerization of MMA initiated by the borohydride
      precursors [Ln(BH(4))(3)(thf)(3)] or [Sm(BH(4))(Cp*)(2)(thf)].

PMID- 18069717
TI  - Emulsion polymerization using Janus particles as stabilizers.

PMID- 18069716
TI  - Explorations of new types of second-order nonlinear optical materials in Cd(Zn)
      VV-TeIV-O Systems.
AB  - Solid-state reactions of zinc(II) or cadmium(II) oxide, V(2)O(5), and TeO(2) at
      high temperature led to two novel quaternary compounds, namely, Zn(3)V(2)TeO(10)
      and Cd(4)V(2)Te(3)O(15). The structure of Zn(3)V(2)TeO(10) is a complicated three
      dimensional (3D) network constructed by the interconnection of ZnO(5), ZnO(6),
      VO(4), and TeO(4) polyhedra via corner- and edge-sharing. Cd(4)V(2)Te(3)O(15)
      with an acentric structure features a 3D network in which the cadmium tellurite
      layers are further interconnected by both "isolated" VO(4) tetrahedra and one
      dimensional (1D) vanadium oxide helical chains. Cd(4)V(2)Te(3)O(15) displays a
      second harmonic generation (SHG) efficiency of about 1.4 times that of KH(2)PO(4)
      (KDP). Both compounds are direct band-gap semiconductors and are transparent in
      the range of 0.6-10.0 mum. Measurements of luminescence indicate that both
      compounds exhibit broad emission bands in the blue-light region.

PMID- 18069718
TI  - Anion binding to resorcinarene-based cavitands: the importance of C-H...anion
      interactions.

PMID- 18069719
TI  - T-20 and T-1249 HIV fusion inhibitors' structure and conformation in solution: a
      molecular dynamics study.
AB  - Fusion of the HIV envelope with the target cell membrane is a critical step of
      the HIV entry into the target cell. Several peptides based on the C-region of HIV
      gp41 have been used in clinical trials as possible HIV fusion inhibitors. Among
      these are T-1249 and T-20 (also known as enfurvitide). Despite recent works, a
      detailed molecular picture of the inhibitory mechanism of these molecules is
      still lacking. These peptides are usually depicted as alpha-helices by analogy
      with the structure of the sequence of the gp41 protein with which they are
      homologous. However, structures like these would be highly unstable in solution
      and thus would not explain, by themselves, the ability that the two fusion
      inhibitors have to become solvated by water and also interact effectively with
      cell membranes. To this effect, extensive molecular dynamics simulations were
      carried out to investigate the structure and conformational behavior of T-1249
      and T-20 in water, as well as shorter homologous peptides CTP and 3f5, which show
      no inhibitory action. We found that the studied inhibitors have no stable
      structure in solution in the time scale studied. Additionally, the solvent
      accessible area varies significantly during the simulation. Our findings suggest
      that these peptides may assume not only one, but several possible sets of
      structures in solution, some of which more adequate to interact with the solvent,
      whereas others might be better suited to interact with cell membranes.
      Interestingly, and in accordance with published experimental studies, we verified
      that T-1249 displays considerably larger alpha-helical structure than T-20.
      Taking into account a recent study with design peptides with increased helicity,
      it is possible that this feature may be related to the increased inhibiting
      efficiency of T-1249 relative to that of T-20.

PMID- 18069720
TI  - Latent transition analysis: inference and estimation.
AB  - Parameters for latent transition analysis (LTA) are easily estimated by maximum
      likelihood (ML) or Bayesian method via Markov chain Monte Carlo (MCMC). However,
      unusual features in the likelihood can cause difficulties in ML and Bayesian
      inference and estimation, especially with small samples. In this study we explore
      several problems in drawing inference for LTA in the context of a simulation
      study and a substance use example. We argue that when conventional ML and
      Bayesian estimates behave erratically, problems often may be alleviated with a
      small amount of prior input for LTA with small samples. This paper proposes a
      dynamic data-dependent prior for LTA with small samples and compares the
      performance of the estimation methods with the proposed prior in drawing
      inference.

PMID- 18069721
TI  - Meta-analysis of continuous outcomes combining individual patient data and
      aggregate data.
AB  - Meta-analysis of individual patient data (IPD) is the gold-standard for
      synthesizing evidence across clinical studies. However, for some studies IPD may
      not be available and only aggregate data (AD), such as a treatment effect
      estimate and its standard error, may be obtained. In this situation, methods for
      combining IPD and AD are important to utilize all the available evidence. In this
      paper, we develop and assess a range of statistical methods for combining IPD and
      AD in meta-analysis of continuous outcomes from randomized controlled trials. The
      methods take either a one-step or a two-step approach. The latter is simple, with
      IPD reduced to AD so that standard AD meta-analysis techniques can be employed.
      The one-step approach is more complex but offers a flexible framework to include
      both patient-level and trial-level parameters. It uses a dummy variable to
      distinguish IPD trials from AD trials and to constrain which parameters the AD
      trials estimate. We show that this is important when assessing how patient-level
      covariates modify treatment effect, as aggregate-level relationships across
      trials are subject to ecological bias and confounding. We thus develop models to
      separate within-trial and across-trials treatment-covariate interactions; this
      ensures that only IPD trials estimate the former, whilst both IPD and AD trials
      estimate the latter in addition to the pooled treatment effect and any between
      study heterogeneity. Extension to multiple correlated outcomes is also
      considered. Ten IPD trials in hypertension, with blood pressure the continuous
      outcome of interest, are used to assess the models and identify the benefits of
      utilizing AD alongside IPD.

PMID- 18069722
TI  - Timing of lung size assessment in the prediction of survival in fetuses with
      diaphragmatic hernia.
AB  - OBJECTIVES: To investigate whether the prediction of postnatal outcome of fetuses
      with isolated congenital diaphragmatic hernia depends on the gestational age at
      assessment using the fetal observed to expected (O/E) lung area to head
      circumference ratio (LHR), by comparing the performance of the test at 22-23
      weeks with that at 32-33 weeks of gestation. METHODS: Following prenatal
      diagnosis of isolated diaphragmatic hernia before 22 weeks, we evaluated the O/E
      LHR at 22-32 weeks and again at 32-33 weeks of gestation. Only cases liveborn
      beyond 34 weeks of gestation and with postnatal follow-up available until
      discharge from the hospital were included. Regression analysis was used to
      examine the effect on postnatal survival of O/E LHR, gestational age at delivery,
      side of the diaphragmatic hernia and intrathoracic position of the liver.
      Wilcoxon rank test for paired samples was used to compare median O/E LHR at 22-23
      weeks and 32-33 weeks, in babies who survived and in those who died. Receiver
      operating characteristics (ROC) curves were constructed for the prediction of
      survival by O/E LHR at 22-23 weeks and at 32-33 weeks. RESULTS: In total, 53
      pairs of measurements could be assessed. Univariate logistic regression analysis
      demonstrated that significant predictors of survival were the presence or absence
      of intrathoracic herniation of the liver, the O/E LHR at 22-23 weeks and the O/E
      LHR at 32-33 weeks of gestation. Multivariate logistic regression analysis
      demonstrated that only O/E LHR at 22-23 weeks or 32-33 weeks provided significant
      independent prediction of survival. The median O/E LHR at 22-23 weeks was not
      significantly different from that at 32-23 weeks either in survivors or in babies
      that subsequently died in the neonatal period (P = 0.25 and P = 0.09,
      respectively). The area under the ROC curve for prediction of postnatal survival
      from the O/E LHR at 22-23 weeks was 0.789 (P < 0.001) and that for prediction
      from the O/E LHR at 32-33 weeks was 0.842 (P < 0.001). CONCLUSIONS: In isolated
      diaphragmatic hernia, O/E LHR measurement at 22-23 weeks as well as at 32-33
      weeks provides useful independent prediction of subsequent survival. The
      prediction of postnatal survival using O/E LHR is independent of the timing of
      assessment.

PMID- 18069723
TI  - Confidence intervals for the risk ratio under inverse sampling.
AB  - In this paper, we investigate various confidence intervals for the risk ratio
      under inverse sampling (also known as negative binomial sampling). Three existing
      confidence intervals (namely, the confidence intervals that are based on
      Fieller's theorem, the delta method and the F-statistic) are reviewed and three
      new confidence intervals (namely, the score, likelihood ratio and saddlepoint
      approximation (SA)-based confidence intervals) are developed. Comparative studies
      among these confidence intervals through Monte Carlo simulations are evaluated in
      terms of their coverage probabilities and expected interval widths under
      different settings. Our simulation results suggest that the SA-based confidence
      interval is generally more appealing. We illustrate these confidence interval
      construction methods with real data sets from a drug comparison study and a
      congenital heart disease study.

PMID- 18069724
TI  - Live-cell analysis of cell penetration ability and toxicity of oligo-arginines.
AB  - Cell penetrating peptides (CPPs) are useful tools to deliver low-molecular-weight
      cargoes into cells; however, their mode of uptake is still controversial. The
      most efficient CPPs belong to the group of arginine-rich peptides, but a
      systematic assessment of their potential toxicity is lacking. In this study we
      combined data on the membrane translocation abilities of oligo-arginines in
      living cells as a function of their chain length, concentration, stability and
      toxicity. Using confocal microscopy analysis of living cells we evaluated the
      transduction frequency of the L-isoforms of oligo-arginines and lysines and then
      monitored their associated toxicity by concomitant addition of propidium iodide.
      Whereas lysines showed virtually no transduction, the transduction ability of
      arginines increased with the number of consecutive residues and the peptide
      concentration, with L-R9 and L-R10 performing overall best. We further compared
      the L- and D-R9 isomers and found that the D-isoform always showed a higher
      transduction as compared to the L-counterpart in all cell types. Notably, the
      transduction difference between D- and L-forms was highly variable between cell
      types, emphasizing the need for protease-resistant peptides as vectors for drug
      delivery. Real-time kinetic analysis of the D- and L-isomers applied
      simultaneously to the cells revealed a much faster transduction for the D
      variant. The latter underlies the fact that the isomers do not mix, and
      penetration of one peptide does not perturb the membrane in a way that gives
      access to the other peptide. Finally, we performed short- and long-term cell
      viability and cell cycle progression analyses with the protease-resistant D-R9.
      Altogether, our results identified concentration windows with low toxicity and
      high transduction efficiency, resulting in fully bioavailable intracellular
      peptides.

PMID- 18069725
TI  - Comments on 'Chi-squared and Fisher-Irwin tests of two-by-two tables with small
      sample recommendations'.

PMID- 18069726
TI  - The impact of a misspecified random-effects distribution on the estimation and
      the performance of inferential procedures in generalized linear mixed models.
AB  - Estimation in generalized linear mixed models (GLMMs) is often based on maximum
      likelihood theory, assuming that the underlying probability model is correctly
      specified. However, the validity of this assumption is sometimes difficult to
      verify. In this paper we study, through simulations, the impact of misspecifying
      the random-effects distribution on the estimation and hypothesis testing in
      GLMMs. It is shown that the maximum likelihood estimators are inconsistent in the
      presence of misspecification. The bias induced in the mean-structure parameters
      is generally small, as far as the variability of the underlying random-effects
      distribution is small as well. However, the estimates of this variability are
      always severely biased. Given that the variance components are the only tool to
      study the variability of the true distribution, it is difficult to assess whether
      problems in the estimation of the mean structure occur. The type I error rate and
      the power of the commonly used inferential procedures are also severely affected.
      The situation is aggravated if more than one random effect is included in the
      model. Further, we propose to deal with possible misspecification by way of
      sensitivity analysis, considering several random-effects distributions. All the
      results are illustrated using data from a clinical trial in schizophrenia.

PMID- 18069727
TI  - Combining data from multiple sources, with applications to environmental risk
      assessment.
AB  - The classical statistical paradigm emphasizes the development and application of
      methods to account for sampling variability. Many modern day applications,
      however, require consideration of other sources of uncertainty that are not so
      easy to quantify. This paper presents a case study involving an assessment of the
      impact of in-utero methylmercury exposure on the Intelligence Quotient (IQ) of
      young children. We illustrate how familiar techniques such as hierarchical
      modeling, Bayesian methods and sensitivity analysis can be used to aid decision
      making in settings that involve substantial uncertainty.

PMID- 18069728
TI  - Bayesian sample size for exploratory clinical trials incorporating historical
      data.
AB  - This paper presents a simple Bayesian approach to sample size determination in
      clinical trials. It is required that the trial should be large enough to ensure
      that the data collected will provide convincing evidence either that an
      experimental treatment is better than a control or that it fails to improve upon
      control by some clinically relevant difference. The method resembles standard
      frequentist formulations of the problem, and indeed in certain circumstances
      involving 'non-informative' prior information it leads to identical answers. In
      particular, unlike many Bayesian approaches to sample size determination, use is
      made of an alternative hypothesis that an experimental treatment is better than a
      control treatment by some specified magnitude. The approach is introduced in the
      context of testing whether a single stream of binary observations are consistent
      with a given success rate p(0). Next the case of comparing two independent
      streams of normally distributed responses is considered, first under the
      assumption that their common variance is known and then for unknown variance.
      Finally, the more general situation in which a large sample is to be collected
      and analysed according to the asymptotic properties of the score statistic is
      explored.

PMID- 18069729
TI  - Re: The design versus the analysis of observational studies for causal effects:
      parallels with the design of randomized trials.

PMID- 18069730
TI  - Pore structural characteristics, size exclusion properties and column performance
      of two mesoporous amorphous silicas and their pseudomorphically transformed MCM
      41 type derivatives.
AB  - Highly ordered mesoporous silicas such as, mobile composition of matter, MCM-41,
      MCM-48, and the SBA-types of materials have helped to a large extent to
      understand the formation mechanisms of the pore structure of adsorbents and to
      improve the methods of pore structural characterization. It still remains an open
      question whether the high order, the regularity of the pore system, and the
      narrow pore size distribution of the materials will lead to a substantial benefit
      when these materials are employed in liquid phase separation processes. MCM-41
      type 10 microm beads are synthesized following the route of pseudomorphic
      transformation of highly porous amorphous silicas. Highly porous silicas and the
      pseudomorphically transformed derivatives are characterized by nitrogen sorption
      at 77 K and by inverse size-exclusion chromatography (ISEC) employing polystyrene
      standards. Applying the network model developed by Grimes, we calculated the pore
      connectivity n(T) of the materials. The value of n(T) varies between the
      percolation threshold of the lattice and values of n(T) > 10, the latter being
      the limiting value above which the material can be considered to be almost
      infinitely connected such that the ISEC behavior of the material calculated with
      the pore network model is the same when calculated with a parallel pore model
      which assumes an infinite connectivity. One should expect that the pore
      connectivity is reflected in the column performance, when these native and
      unmodified materials are packed into columns and tested with low molecular weight
      analytes in the Normal Phase LC mode. As found in a previous study on monolithic
      silicas and highly porous silicas, the slope of the plate height (HETP) - linear
      velocity (u) curve decreased significantly with enhanced pore connectivity of the
      materials. First results on the pseudomorphically transformed MCM-41 type silicas
      and their highly porous amorphous precursors showed that (i) the transformation
      did not change the pore connectivity (within the limits detectable by ISEC) from
      the starting material to the final product and (ii) the slope of the HETP versus
      u curve for dibutylphtalate did not change significantly after the pseudomorphic
      transformation.

PMID- 18069731
TI  - Isocratic chromatography of resveratrol and piceid after previous generation of
      fluorescent photoproducts: wine analysis without sample preparation.
AB  - Resveratrol and its 3-glucoside (piceid), are stilbene-like molecules produced by
      plants. Both of them are weakly fluorescent, but highly fluorescent compounds are
      obtained when their hydroethanolic solutions are UV-irradiated, which implies a
      substantial improvement in the sensitivity of analytical methods. Experimental
      design (central composite design) together with the response surface methodology
      have been used to find optimum conditions for the fast, sensitive, and precise
      chromatographic analysis (with isocratic elution) of resveratrol and piceid in
      wine samples. These compounds have been UV-transformed into their respective
      photoproducts, which have been separated in a C18 column (Novapack C(18) 150x3.9
      mm, 4 microm) by isocratic elution, using a mobile phase made up of acetonitrile
      and 4.1 vol% aqueous acetic acid, 19:81 v/v, at a flow rate of 0.8 mL/min, and
      fluorimetrically detected at 364 nm (lambda(exc) = 260 nm). Detection limits (S/N
      = 3) are 0.29 and 0.28 microg/L for resveratrol and piceid, respectively. The
      method has been applied to the analysis of these compounds in wine samples
      without a clean-up step. The analysis is completed in only 20 min. The standard
      addition method has been applied to the analysis of a commercial red wine and
      average recoveries near 100% were obtained for resveratrol and piceid. Three wine
      pools were satisfactorily analysed by external calibration.

PMID- 18069732
TI  - Membrane-bound peptides from V-ATPase subunit a do not interact with an indole
      type inhibitor.
AB  - The V-ATPases are ATP-dependent proton pumps, found in virtually all cells,
      responsible for acidification of organelles and energizing of plasma membranes.
      Its role in diseases, such as osteoporosis and metastatic cancer, makes the V
      ATPase a potential drug target. Short synthetic peptides that are presented here
      mimic the 7th transmembrane domain (TM7) of subunit a (Vph1p) of Saccharomyces
      cerevisiae V-ATPase, an essential part of the membrane-bound VO domain, where
      proton translocation takes place. The peptides adopt a transmembrane
      configuration only in membranes containing anionic lipids, stressing the
      importance of strong interfacial anchoring by the flanking lysines. Peptide P1,
      which contains the essential arginine R735, is monomeric, whereas peptide P2,
      which lacks this extra charge, tends to aggregate in the membrane. SB 242784,
      which is a highly potent inhibitor of V-ATPase, does not show any interaction
      with the peptides, indicating that TM7 alone is not sufficient for inhibitor
      binding.

PMID- 18069733
TI  - Comments on 'Randomization with a posteriori constraints: description and
      properties'.

PMID- 18069734
TI  - Comments on 'Fixed vs random effects meta-analysis in rare event studies: the
      rosiglitazone link with myocardial infarction and cardiac death'.

PMID- 18069739
TI  - Structural changes of casein micelles in a calcium gradient film.
AB  - Calcium gradients are prepared by sequentially filling a micropipette with casein
      solutions of varying calcium concentration and spreading them on glass slides.
      The casein film is formed by a solution casting process, which results in a
      macroscopically rough surface. Microbeam grazing incidence small-angle X-ray
      scattering (microGISAXS) is used to investigate the lateral size distribution of
      three main components in casein films: casein micelles, casein mini-micelles, and
      micellar calcium phosphate. At length scales within the beam size the film
      surface is flat and detection of size distribution in a macroscopic casein
      gradient becomes accessible. The model used to analyze the data is based on a set
      of three log-normal distributed particle sizes. Increasing calcium concentration
      causes a decrease in casein micelle diameter while the size of casein mini
      micelles increases and micellar calcium phosphate particles remain unchanged.

PMID- 18069740
TI  - Extraction, separation, and detection methods for phenolic acids and flavonoids.
AB  - The impetus for developing analytical methods for phenolic compounds in natural
      products has proved to be multifaceted. Hundreds of publications on the analysis
      of this category of compounds have appeared over the past two decades.
      Traditional and more advanced techniques have come to prominence for sample
      preparation, separation, detection, and identification. This review provides an
      updated and extensive overview of methods and their applications in natural
      product matrices and samples of biological origin. In addition, it critically
      appraises recent developments and trends, and provides selected representative
      bibliographic examples.

PMID- 18069743
TI  - Simultaneous determination of iridoids, phenolic acids, flavonoids, and saponins
      in Flos Lonicerae and Flos Lonicerae Japonicae by HPLC-DAD-ELSD coupled with
      principal component analysis.
AB  - A method, HPLC coupled with diode-array and evaporative light scattering
      detectors (HPLC-DAD-ELSD), was newly developed to evaluate the quality of Flos
      Lonicerae (FL) and Flos Lonicerae Japonicae (FLJ), through a simultaneous
      determination of multiple types of bioactive components. By employing DAD, the
      detection wavelengths were set at 240 nm for the determination of iridoids, 330
      nm for phenolic acids, and 360 nm for flavonoids, respectively. While ELSD,
      connected in series after DAD, was applied to the determination of saponins. This
      assay was fully validated with respect to precision, repeatability, and accuracy.
      Moreover, principal component analysis (PCA) was used for the similarity
      evaluation of different samples, and it was proven straightforward and reliable
      to differentiate FL and FLJ samples from different origins. For PCA, two
      principal components have been extracted. Principal component 1 (PC1) influences
      the separation between different sample sets, capturing 54.598% variance, while
      principal component 2 (PC2) affects differentiation within sample sets, capturing
      12.579% variance. In conclusion, simultaneous quantification of bioactive
      components by HPLC-DAD-ELSD coupled with PCA would be a well-acceptable strategy
      to differentiate the sources and to comprehensively control the quality of the
      medicinal plants FL and FLJ.

PMID- 18069744
TI  - The use of doxycycline as a protectant against sulphur mustard in HaCaT cells.
AB  - As part of an ongoing programme on medical countermeasures against the chemical
      warfare agent sulphur mustard (HD) and set against the background of the
      involvement of matrix metalloproteinases (MMPs) in the pathology of HD-induced
      vesication processes, the potentially beneficial effects of doxycycline on cell
      attachment was determined in confluent HaCaT cell cultures exposed to HD.
      Doxycycline was found to inhibit to a significant extent the tendency of HD
      exposed cells to detach from the growth substrate, however, analysis of the
      metabolic activity of the adherent cells indicated that doxycycline treatment did
      not maintain cell viability. It was confirmed that apoptosis was the predominant
      mode of HD-induced cell death. The results suggested that doxycycline and other
      MMP inhibitors may have a role to play in therapeutic intervention against HD
      exposure, but only as part of a combination therapy. The specific value of
      protease inhibitors in this capacity remains to be determined.

PMID- 18069745
TI  - Investigating trial and treatment heterogeneity in an individual patient data
      meta-analysis of survival data by means of the penalized maximum likelihood
      approach.
AB  - In a meta-analysis combining survival data from different clinical trials, an
      important issue is the possible heterogeneity between trials. Such intertrial
      variation can not only be explained by heterogeneity of treatment effects across
      trials but also by heterogeneity of their baseline risk. In addition, one might
      examine the relationship between magnitude of the treatment effect and the
      underlying risk of the patients in the different trials. Such a scenario can be
      accounted for by using additive random effects in the Cox model, with a random
      trial effect and a random treatment-by-trial interaction. We propose to use this
      kind of model with a general correlation structure for the random effects and to
      estimate parameters and hazard function using a semi-parametric penalized
      marginal likelihood method (maximum penalized likelihood estimators). This
      approach gives smoothed estimates of the hazard function, which represents
      incidence in epidemiology. The idea for the approach in this paper comes from the
      study of heterogeneity in a large meta-analysis of randomized trials in patients
      with head and neck cancers (meta-analysis of chemotherapy in head and neck
      cancers) and the effect of adding chemotherapy to locoregional treatment. The
      simulation study and the application demonstrate that the proposed approach
      yields satisfactory results and they illustrate the need to use a flexible
      variance-covariance structure for the random effects.

PMID- 18069746
TI  - Tilted peptides: a structural motif involved in protein membrane insertion?
AB  - Tilted peptides are short hydrophobic protein fragments characterized by an
      asymmetric distribution of their hydrophobic residues when helical. They are able
      to interact with a hydrophobic/hydrophilic interface (such as a lipid membrane)
      and to destabilize the organized system into which they insert. They were
      detected in viral fusion proteins and in proteins involved in different
      biological processes involving membrane insertion or translocation of the protein
      in which they are found. In this paper, we have analysed different protein
      domains related to membrane insertion with regard to their tilted properties.
      They are the N-terminal signal peptide of the filamentous haemagglutinin (FHA), a
      Bordetella pertussis protein secreted in high amount and the hydrophobic domain
      from proteins forming pores (i.e. ColIa, Bax and Bcl-2). From the predictions and
      the experimental approaches, we suggest that tilted peptides found in those
      proteins could have a more general role in the mechanism of
      insertion/translocation of proteins into/across membranes. For the signal
      sequences, they could help the protein machinery involved in protein secretion to
      be more active. In the case of toroidal pore formation, they could disturb the
      lipids, facilitating the insertion of the other more hydrophilic helices.

PMID- 18069747
TI  - High-energy collision-induced dissociation of phosphopeptides using a multi-turn
      tandem time-of-flight mass spectrometer 'MULTUM-TOF/TOF'.

PMID- 18069748
TI  - Coupling desorption electrospray ionisation and neutral desorption/extractive
      electrospray ionisation with a travelling-wave based ion mobility mass
      spectrometer for the analysis of drugs.
AB  - Desorption electrospray ionisation (DESI) and neutral desorption/extractive
      electrospray ionisation (EESI) have been coupled to a hybrid quadrupole
      travelling-wave (T-Wave)-based ion mobility time-of-flight mass spectrometer for
      the direct accurate mass analysis of active ingredients formulated into
      pharmaceutical samples. The collision cross-section measurements of polyethylene
      glycol (PEG) excipients detected in one formulation were estimated and compared
      with published data. These estimated collision cross-sections of the PEG species
      showed good agreement with published data.

PMID- 18069749
TI  - Mass spectrometric characterization of beta-caryophyllene ozonolysis products in
      the aerosol studied using an electrospray triple quadrupole and time-of-flight
      analyzer hybrid system and density functional theory.
AB  - The components of the organic aerosol formed due to gas-phase beta-caryophyllene
      ozonolysis were characterized by the use of a triple quadrupole and time-of
      flight analyzer hybrid system coupled to an electrospray ionization source
      operated in the negative ion mode. A reversed-phase high-performance liquid
      chromatography (HPLC) column was used to achieve chromatographic separations at
      neutral pH which has been proved to induce ionization of organic compounds
      bearing aldehyde moieties. In addition to the detected oxo- and dicarboxylic
      acids, isomeric oxidation products, which bear multi-functional groups such as
      aldehyde, carbonyl and hydroxyl groups, could be differentiated by examining
      their corresponding collision-induced dissociation (CID) fragmentation pathways.
      Proposed fragmentation mechanisms were drawn for the experimentally observed
      fragmentation pathways in all the CID experiments. Cyclic oxidation products
      could also be discerned and their fragmentation behaviour under low energy
      collisional conditions was studied in detail. Gas-phase deprotonation potentials
      were calculated by the use of DFT B3LYP/6-311+G(2d,p)//B3LYP/6-31+G(d) + ZPVE to
      estimate the most thermodynamically favourable deprotonation site for efficient
      negative ion formation in the ion source. The optimized gas-phase geometries for
      the most prominent oxidation products reveal a strong intramolecular interaction
      between the upper and lower C4 carbon chains, which are formed after the
      decomposition of the primary ozonide generated by ozone attack of the reactive
      endocyclic C==C bond.

PMID- 18069750
TI  - Endoscopic treatment of chronic pancreatitis.
AB  - Treatment of chronic pancreatitis has been exclusively surgical for a long time.
      Recently, endoscopic therapy has become widely used as a primary therapeutic
      option. Initially performed for drainage of pancreatic cysts and pseudocysts,
      endoscopic treatments were adapted to biliary and pancreatic ducts stenosis.
      Pancreatic sphincterotomy which allows access to pancreatic ducts was firstly
      reported. Secondly, endoscopic methods of stenting, dilatation, and stones
      extraction of the bile ducts were applied to pancreatic ducts. Nevertheless, new
      improvements were necessary: failures of pancreatic stone extraction justified
      the development of extra-corporeal shock wave lithotripsy; dilatation of
      pancreatic stenosis was improved by forage with a new device; moreover
      endosonography allowed guidance for celiac block, gastro-cystostomy, duodeno
      cystostomy and pancreatico-gastrostomy. Although endoscopic treatments are more
      and more frequently accepted, indications are still debated.

PMID- 18069751
TI  - Smoking in inflammatory bowel diseases: good, bad or ugly?
AB  - Smoking is an important environmental factor in inflammatory bowel disease (IBD),
      having different effects in ulcerative colitis (UC) and Crohn's disease (CD). A
      recent meta-analysis partially confirmed previous findings that smoking was found
      to be protective against ulcerative colitis and, after onset of the disease,
      might improve its course, decreasing the need for colectomy. However, smoking
      increases the risk of developing CD and worsens its course, increasing the need
      for steroids, immunosuppressants and re-operations. Smoking cessation aggravates
      ulcerative colitis and improves CD. Data are however, largely conflictive as well
      as the potential mechanisms involved in this dual relationship are still unknown.
      In this review article, the authors review the role of smoking in inflammatory
      bowel diseases.

PMID- 18069753
TI  - Telbivudine: a new treatment for chronic hepatitis B.
AB  - Three hundred and fifty million people worldwide are estimated to be chronically
      infected with hepatitis B virus. 15%-40% of these subjects will develop
      cirrhosis, liver failure or hepatocellular carcinoma during their life. The
      treatment of chronic hepatitis B has improved dramatically over the last decade
      merits to the advent of nucleoside/nucleotide analogues and the use of pegylated
      interferons. Approved drugs for chronic hepatitis B treatment include: standard
      interferon-alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir
      dipivoxil, and entecavir. Unfortunately, these agents are not effective in all
      patients and are associated with distinct side effects. Interferons have numerous
      side effects and nucleoside or nucleotide analogues, which are well tolerated,
      need to be used for prolonged periods, even indefinitely. However, prolonged
      treatment with nucleoside or nucleotide analogues is associated with a high rate
      of resistance. Telbivudine is a novel, orally administered nucleoside analogue
      for use in the treatment of chronic hepatitis B. In contrast to other nucleoside
      analogues, Telbivudine has not been associated with inhibition of mammalian DNA
      polymerase with mitochondrial toxicity. Telbivudine has demonstrated potent
      activity against hepatitis B with a significantly higher rate of response and
      superior viral suppression compared with lamivudine, the standard treatment.
      Telbivudine has been generally well tolerated, with a low adverse effect profile,
      and at its effective dose, no dose-limiting toxicity has been observed.
      Telbivudine is one of the most potent antiviral agents for chronic hepatitis B
      virus and was approved by the FDA in late 2006.

PMID- 18069752
TI  - Small bowel capsule endoscopy in 2007: indications, risks and limitations.
AB  - Capsule endoscopy has revoluzionized the study of the small bowel by providing a
      reliable method to evaluate, endoscopically, the entire small bowel. In the last
      six years several papers have been published exploring the possible role of this
      examination in different clinical conditions. At the present time capsule
      endoscopy is generally recommended as a third examination, after negative
      bidirectional endoscopy, in patients with obscure gastrointestinal bleeding. A
      growing body of evidence suggests also an important role for this examination in
      other clinical conditions such as Crohn's disease, celiac disease, small bowel
      polyposis syndromes or small bowel tumors. The main complication of this
      examination is the retention of the device at the site of a previously unknown
      small bowel stricture. However there are also some other open issues mainly due
      to technical limitations of this tool (which is not driven from remote control,
      is unable to take biopsies, to insufflate air, to suck fluids or debris and
      sometimes to correctly size and locate lesions). The recently developed double
      balloon enteroscope, owing to its capability to explore a large part of the small
      bowel and to take targeted biopsies, although being invasive and time consuming,
      can overcome some limitations of capsule endoscopy. At the present time, in the
      majority of clinical conditions (i.e. obscure GI bleeding), the winning strategy
      seems to be to couple these two techniques to explore the small bowel in a
      painless, safe and complete way (with capsule endoscopy) and to define and treat
      the lesions identified (with double balloon enteroscopy).

PMID- 18069754
TI  - Basic and clinical aspects of osteoporosis in inflammatory bowel disease.
AB  - Low bone mineral density and the increased risk of fracture in gastrointestinal
      diseases have a multifactorial pathogenesis. Inflammatory bowel disease (IBD) has
      been associated with an increased risk of osteoporosis and osteopenia and
      epidemiologic studies have reported an increased prevalence of low bone mass in
      patients with IBD. Certainly, genetics play an important role, along with other
      factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid
      therapy in IBD and other lifestyle factors. At a molecular level the
      proinflammatory cytokines that contribute to the intestinal immune response in
      IBD are known to enhance bone resorption. There are genes influencing osteoblast
      function and it is likely that LRP5 may be involved in the skeletal development.
      Also the identification of vitamin D receptors (VDRs) and some of its
      polymorphisms have led to consider the possible relationships between them and
      some autoimmune diseases and may be involved in the pathogenesis through the
      exertion of its immunomodulatory effects during inflammation. Trying to explain
      the physiopathology we have found that there is increasing evidence for the
      integration between systemic inflammation and bone loss likely mediated via
      receptor for activated nuclear factor kappa-B (RANK), RANK-ligand, and
      osteoprotegerin, proteins that can affect both osteoclastogenesis and T-cell
      activation. Although glucocorticoids can reduce mucosal and systemic
      inflammation, they have intrinsic qualities that negatively impact on bone mass.
      It is still controversial if all IBD patients should be screened, especially in
      patients with preexisting risk factors for bone disease. Available methods to
      measure BMD include single energy x-ray absorptiometry, DXA, quantitative
      computed tomography (QCT), radiographic absorptiometry, and ultrasound. DXA is
      the establish method to determine BMD, and routinely is measured in the hip and
      the lumbar spine. There are several treatments options that have proven their
      effectiveness, while new emergent therapies such as calcitonin and teriparatide
      among others remain to be assessed.

PMID- 18069755
TI  - Re-expression of methylation-induced tumor suppressor gene silencing is
      associated with the state of histone modification in gastric cancer cell lines.
AB  - AIM: To identify the relationship between DNA hyper-methylation and histone
      modification at a hyperme-thylated, silenced tumor suppressor gene promoter in
      human gastric cancer cell lines and to elucidate whether alteration of DNA
      methylation could affect histone modification. METHODS: We used chromatin
      immunoprecipitation (ChIP) assay to assess the status of histone acetylation and
      methylation in promoter regions of the p16 and mutL homolog 1 (MLH1) genes in 2
      gastric cancer cell lines, SGC-7901 and MGC-803. We used methylation-specific PCR
      (MSP) to evaluate the effect of 5-Aza-2'-deoxycytidine (5-Aza-dC), trichostatin A
      (TSA) or their combination treatment on DNA methylation status. We used RT-PCR to
      determine whether alterations of histone modification status after 5-Aza-dC and
      TSA treatment are reflected in gene expression. RESULTS: For the p16 and MLH1
      genes in two cell lines, silenced loci associated with DNA hypermethylation were
      characterized by histone H3-K9 hypoacetylation and hypermethylation and histone
      H3-K4 hypomethylation. Treatment with TSA resulted in moderately increased
      histone H3-K9 acetylation at the silenced loci with no effect on histone H3-K9
      methylation and minimal effects on gene expression. In contrast, treatment with 5
      Aza-dC rapidly reduced histone H3-K9 methylation at the silenced loci and
      resulted in reactivation of the two genes. Combined treatment with 5-Aza-dC and
      TSA was synergistic in reactivating gene expression at the loci showing DNA
      hypermethylation. Similarly, histone H3-K4 methylation was not affected after TSA
      treatment, and increased moderately at the silenced loci after 5-Aza-dC
      treatment. CONCLUSION: Hypermethylation of DNA in promoter CpG islands is related
      to transcriptional silencing of tumor suppressor genes. Histone H3-K9 methylation
      in different regions of the promoters studied correlates with DNA methylation
      status of each gene in gastric cancer cells. However, histone H3-K9 acetylation
      and H3-K4 methylation inversely correlate with DNA methylation status of each
      gene in gastric cancer cells. Alteration of DNA methylation affects histone
      modification.

PMID- 18069756
TI  - Protective effects of erythropoietin against acute lung injury in a rat model of
      acute necrotizing pancreatitis.
AB  - AIM: To investigate the effect of exogenous erythro-poietin (EPO) administration
      on acute lung injury (ALI) in an experimental model of sodium taurodeoxycholate-
      induced acute necrotizing pancreatitis (ANP). METHODS: Forty-seven male Wistar
      albino rats were randomly divided into 7 groups: sham group (n = 5), 3 ANP groups
      (n = 7 each) and 3 EPO groups (n = 7 each). ANP was induced by retrograde
      infusion of 5% sodium taurodeoxycholate into the common bile duct. Rats in EPO
      groups received 1000 U/kg intramuscular EPO immediately after induction of ANP.
      Rats in ANP groups were given 1 mL normal saline instead. All animals were
      sacrificed at postoperative 24 h, 48 h and 72 h. Serum amilase, IL-2, IL-6 and
      lung tissue malondialdehyde (MDA) were measured. Pleural effusion volume and
      lung/body weight (LW/BW) ratios were calculated. Tissue levels of TNF-alpha, IL-2
      and IL-6 were screened immunohistochemically. Additionally, ox-LDL accumulation
      was assessed with immune-fluorescent staining. Histopathological alterations in
      the lungs were also scored. RESULTS: The mean pleural effusion volume, calculated
      LW/BW ratio, serum IL-6 and lung tissue MDA levels were significantly lower in
      EPO groups than in ANP groups. No statistically significant difference was
      observed in either serum or tissue values of IL-2 among the groups. The level of
      tumor necrosis factor-alpha (TNF-alpha) and IL-6 and accumulation of ox-LDL were
      evident in the lung tissues of ANP groups when compared to EPO groups,
      particularly at 72 h. Histopathological evaluation confirmed the improvement in
      lung injury parameters after exogenous EPO administration, particularly at 48 h
      and 72 h. CONCLUSION: EPO administration leads to a significant decrease in ALI
      parameters by inhibiting polymorphonuclear leukocyte (PMNL) accumulation,
      decreasing the levels of proinflammatory cytokines in circulation, preserving
      microvascular endothelial cell integrity and reducing oxidative stress-associated
      lipid peroxidation and therefore, can be regarded as a cytoprotective agent in
      ANP-induced ALI.

PMID- 18069758
TI  - Heterozygous nucleotide-binding oligomerization domain-2 mutations affect
      monocyte maturation in Crohn's disease.
AB  - AIM: To investigate the function of monocytes in Crohn's disease (CD) patients
      and to correlate this with disease-associated nucleotide-binding oligomerization
      domain-2 (NOD2) gene variants. METHODS: Monocytes from 47 consecutively referred
      CD patients and 9 healthy blood donors were cultured with interleukin (IL)-4 and
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and stimulated with
      lipopolysaccharide (LPS) or muramyldipeptide (MDP), the putative ligand of NOD2.
      RESULTS: We found that monocytes from CD patients differentiated in vitro to
      mature dendritic cells (DCs), as determined by immunophenotype and morphology.
      NOD2 genotype was assessed in all subjects, and we observed high CD86 expression
      on immature and LPS-stimulated DCs in NOD2 mutated CD patients, as compared with
      wtNOD2 CD patients and controls. By contrast, CD86 expression levels of DCs
      induced to maturity with MDP derived from NOD2-mutated subjects were comparable
      to those of normal subjects. The amount of IL-12p70 in patient-cell cultures was
      larger than in controls after LPS treatment, but not after treatment with MDP.
      CONCLUSION: Our results suggest that DCs obtained from patients with mutations in
      the NOD2 gene display an activated phenotype characterized by high CD86
      expression, but have a diminished response to MDP when compared to the terminal
      differentiation phase. We speculate that the altered differentiation of monocytes
      might lead to an imbalance between inflammation and the killing ability of
      monocytes, and may be relevant to the pathogenesis of CD.

PMID- 18069757
TI  - Carbon liberated from CO-releasing molecules attenuates leukocyte infiltration in
      the small intestine of thermally injured mice.
AB  - AIM: To determine whether Carbon (CO) liberated from CO-releasing molecules
      attenuates leukocyte infiltration in the small intestine of thermally injured
      mice. METHODS: Thirty-six mice were assigned to four groups. Mice in the sham
      group (n = 9) were underwent to sham thermal injury; mice in the burn group (n =
      9) received 15% total body surface area full-thickness thermal injury; mice in
      the burn + CORM-2 group (n = 9) were underwent to the same thermal injury with
      immediate administration of tricarbonyldichlororuthenium (II) dimer CORM-2 (8
      mg/kg, i.v.); and mice in the burn+DMSO group (n = 9) were underwent to the same
      thermal injury with immediate administration of 160 muL bolus injection of 0.5%
      DMSO/saline. Histological alterations and granulocyte infiltration of the small
      intestine were assessed. Polymorphonuclear neutrophil (PMN) accumulation
      (myeloperoxidase assay) was assessed in mice mid-ileum. Activation of nuclear
      factor (NF)-kappa B, expression levels of intercellular adhesion molecule-1 (ICAM
      1) and inducible heme oxygenase in mid-ileum were assessed. RESULTS: Treatment of
      thermally injured mice with CORM-2 attenuated PMN accumulation and prevented
      activation of NF-kappa B in the small intestine. This was accompanied by a
      decrease in the expression of ICAM-1. In parallel, burn-induced granulocyte
      infiltration in mid-ileum was markedly decreased in the burn mice treated with
      CORM-2. CONCLUSION: CORM-released CO attenuates leukocyte infiltration in the
      small intestine of thermally injured mice by interfering with NF-kappa B
      activation and protein expression of ICAM-1, and therefore suppressing the pro
      adhesive phenotype of endothelial cells.

PMID- 18069759
TI  - Accurate positioning of the 24-hour pH monitoring catheter: agreement between
      manometry and pH step-up method in two patient positions.
AB  - AIM: To investigate the agreement between esophageal manometry and pH step-up
      method in two different patient positions. METHODS: Eighteen subjects were
      included in the study. First, the distance from the nose to the proximal border
      of the lower esophageal sphincter (LES) was measured manometrically. Then a
      different investigator, who was blinded to the results of the first study,
      measured the same distance using the pH step-up method, with the patient in both
      upright and supine positions. An assessment of agreement between the two
      techniques was performed. RESULTS: In the supine position, the measurement of
      only one subject was outside the range accepted for correct positioning (< or = 3
      cm distal or proximal to the LES). In the upright position, errors in measurement
      were recognized in five subjects. Bland-Altman plots revealed good agreement
      between measurements obtained manometrically and by the pH-step up method with
      the patient in the supine position. CONCLUSION: In the case of nonavailability of
      manometric detection device, the pH step-up method can facilitate the positioning
      of the 24 h pH monitoring catheter with the patient in the supine position. This
      should increase the use of pH-metry in clinical practice for subjects with
      suspected gastroesophageal reflux disease if our results are supported by further
      studies.

PMID- 18069760
TI  - Combination of allopurinol and hyperbaric oxygen therapy: a new treatment in
      experimental acute necrotizing pancreatitis?
AB  - AIM: To investigate the individual and combined effects of allopurinol and
      hyperbaric oxygen (HBO) therapy on biochemical and histopathological changes,
      oxidative stress, and bacterial translocation (BT) in the experimental rat acute
      pancreatitis (AP). METHODS: Eighty-five Sprague-Dawley rats were included in the
      study. Fifteen of the eighty-five rats were used as controls (sham, Group I). AP
      was induced via intraductal taurocholate infusion in the remaining seventy rats.
      Rats that survived to induction of acute necrotizing pancreatitis were randomized
      into four groups. Group II received saline, Group III allopurinol, Group IV
      allopurinol plus HBO and Group V HBO alone. Serum amylase levels, oxidative
      stress parameters, BT and histopathologic scores were determined. RESULTS: Serum
      amylase levels were lower in Groups III, IV and V compared to Group II (974 +/-
      110, 384 +/- 40, 851 +/- 56, and 1664 +/- 234 U/L, respectively, P < 0.05, for
      all). Combining the two treatment options revealed significantly lower median [25
      75 percentiles] histopathological scores when compared to individual
      administrations (13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group,
      and 6 [4.5-7.5] in combined group, P < 0.01). Oxidative stress markers were
      significantly better in all treatment groups compared to the controls. Bacterial
      translocation into the pancreas and mesenteric lymph nodes was lower in Groups
      III, IV and V compared to Group II (54%, 23%, 50% vs 100% for translocation to
      pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes,
      respectively, P < 0.05 for all). CONCLUSION: The present study confirms the
      benefit of HBO and allopurinol treatment when administered separately in
      experimental rat AP. Combination of these treatment options appears to prevent
      progression of pancreatic injury parameters more effectively.

PMID- 18069761
TI  - Early diagnosis and prediction of severity in acute pancreatitis using the urine
      trypsinogen-2 dipstick test: a prospective study.
AB  - AIM: To evaluate the use of the trypsinogen-2 dipstick (Actim Pancreatitis) test
      for early diagnosis and prediction of severity in acute pancreatitis (AP).
      METHODS: Ninety-two patients with AP were included in this study. The control
      group was 25 patients who had acute abdominal pain from non-pancreatic causes.
      Urine trypsinogen-2 dipstick test (UTDT) and conventional diagnostic tests were
      performed in all patients. Patients were divided by the Atlanta classification
      into two groups as having mild or severe pancreatitis. RESULTS: UTDT was positive
      in 87 (94.6%) of the AP patients and in two (8%) controls (P < 0.05). Positive
      UTDT was found in 61 (92.4%) of 66 (71.7%) patients with mild pancreatitis and in
      all (100%) of the 26 (28.3%) with severe pancreatitis (P > 0.05). UTDT positivity
      lasted longer in severe pancreatitis compared with that in mild pancreatitis (6.2
      +/- 2.5 d vs 2.0 +/- 1.43 d, P < 0.05). The sensitivity, specificity, positive
      predictive value, negative predictive value (NPV), positive likelihood ratio
      (PLR) and negative likelihood ratio (NLR) of UTDT were 91%, 72%, 96.6%, 70.4%,
      3.4 and 0.1, respectively. CONCLUSION: UTDT is a simple, rapid and reliable
      method for use on admission. It has high specificity and low NLR for early
      diagnosis and prediction of severity in AP. However, its relatively low NPV does
      not allow trypsinogen-2 dipstick test to be a stand-alone tool for diagnosis of
      acute pancreatitis; the use of other conventional diagnostic tools remains a
      requirement.

PMID- 18069762
TI  - Effect of Breathwalk on body composition, metabolic and mood state in chronic
      hepatitis C patients with insulin resistance syndrome.
AB  - AIM: To identify the anthropometric, metabolic and mood state in hepatitis C
      virus (HCV)-infected patients from the west of Mexico and to evaluate the effect
      of Breathwalk (BW), a combination of walking, synchronized breathing and focussed
      attention, on those patients. METHODS: In an experimental study, 17 patients with
      serological and molecular diagnosis of HCV, not receiving pharmacological
      treatment, were studied. One hour sessions of BW were practiced 3 times at week
      for six months. Body composition was assessed by electric impedance. Biochemical
      profiles and insulin resistance (IR) risk was assessed by conventional methods.
      Mood state was evaluated with specific and open questions at the beginning and at
      the end of the program. RESULTS: Seventy percent of patients were overweight or
      obese, and 77% of the patients presented with IR at the beginning of the study.
      Improvements were observed at the 3rd mo, and statistically significant
      differences were recorded at the 6th mo using the fitness score (76 vs 83, P <
      0.01), in alanine aminotransferase (ALT) (106 +/- 93 U/L vs 59 +/- 32 U/L, P <
      0.01), total bilirubin (0.09 +/- 1 mg/dL vs 0.62 +/- 0.2 mg/dL, P < 0.01),
      ALT/AST ratio (1.04 vs 0.70, P < 0.01), triglycerides (165 +/- 86 mg/dL vs 124 +/
      49 mg/dL, P < 0.01) and the IR risk (4.0 vs 2.7). Most patients (88%) indicated
      to feel better at the end of BW (P < 0.01). CONCLUSION: Breathwalk has an
      important effect on body composition, lipid profile and liver enzymes. It is also
      easy, inexpensive and has a beneficial effect on metabolic and mood state in HCV
      patients.

PMID- 18069763
TI  - Inflammatory cytokines suppress arylamine N-acetyltransferase 1 in
      cholangiocarcinoma cells.
AB  - AIM: To evaluate the effect of inflammatory cytokines on arylamine N
      acetyltransferase 1 (NAT1), which is a phase-II enzyme involved in the
      biotransformation of aromatic and heterocyclic amines found in food, drugs and
      the environment. METHODS: Human cholangiocarcinoma KKU-100 cells were treated
      with a mixture of proinflammatory cytokines (interferon-gamma, interleukin-1 beta
      and tumor necrosis factor-alpha) for 48 h, and the effect on NAT1 activity was
      assessed by high performance liquid chromatography, while NAT1 expression was
      determined by reverse-transcription polymerase chain reaction. The oxidative
      stress on the cells was examined by the formation of nitric oxide, superoxide
      anion and glutathione (GSH) levels. The cells were also treated with S-nitroso
      glutathione (GSNO), a nitric oxide donor, to see if the responses were similar to
      those obtained with the inflammatory cytokines. RESULTS: Cytokines suppressed
      NAT1 activity, reducing the Vmax without affecting the Km. Cytokines also had a
      significant impact on the induction of nitric oxide production and in reducing
      the redox ratios of glutathione (GSH) and GSH disulfide. Treatment with GSNO for
      2-48 h reduced NAT1 activity without affecting the GSH ratio. Moreover,
      inflammatory cytokines and GSNO suppressed NAT1 mRNA expression. CONCLUSION:
      These findings indicate an association between inflammation and suppression of
      NAT1, which perhaps contributes to chemical-mediated toxicity and carcinogenesis.

PMID- 18069764
TI  - Predictors of premature delivery in patients with intrahepatic cholestasis of
      pregnancy.
AB  - AIM: To evaluate the predictive value of clinical symptoms and biochemical
      parameters for prematurity in intrahepatic cholestasis of pregnancy (ICP).
      METHODS: Sixty symptomatic patients with ICP were included in this retrospective
      analysis. Preterm delivery was defined as delivery before 37 wk gestation.
      Predictors of preterm delivery were disclosed by binary multivariate logistic
      regression analysis. RESULTS: Mean time of delivery was 38.1 +/- 1.7 wk. No
      stillbirths occurred. Premature delivery was observed in eight (13.3%) patients.
      Total fasting serum bile acids were higher (47.8 +/- 15.2 vs 41.0 +/- 10.0
      mumol/L, P < 0.05), and pruritus tended to start earlier (29.0 +/- 3.9 vs 31.6 +/
      3.3 wk, P = 0.057) in patients with premature delivery when compared to those
      with term delivery. Binary multivariate logistic regression analysis revealed
      that early onset of pruritus (OR 1.70, 95% CI 1.23-2.95, P = 0.038) and serum
      bile acid (OR 2.13, 95% CI 1.13-3.25, P = 0.013) were independent predictors of
      preterm delivery. CONCLUSION: Early onset of pruritus and high levels of serum
      bile acids predict preterm delivery in ICP, and define a subgroup of patients at
      risk for poor neonatal outcome.

PMID- 18069765
TI  - Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for
      advanced colorectal cancer that progressed after oxaliplatin and irinotecan
      chemotherapy: a pilot study.
AB  - AIM: To evaluate the combination of bevacizumab with infusional 5-fluorouracil (5
      FU), leucovorin (LV) and irinotecan (FOLFIRI) in patients with advanced
      colorectal cancer (CRC) pretreated with combination regimens including irinotecan
      and oxaliplatin. METHODS: Fourteen patients (median age 56 years) with advanced
      CRC, all having progressed after oxaliplatin- and irinotecan-based combination
      chemotherapy, were enrolled in this study. Patients were treated with 2 h
      infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for
      90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400
      mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive
      days every 14 d. RESULTS: The median number of cycles of chemotherapy was six
      (range 3-12). The response rate was 28.5%, one patient had a complete response,
      and three patients had a partial response. Eight patients had stable disease. The
      median time to progression was 3.9 mo (95% CI 2.0-8.7), and the median overall
      survival was 10.9 mo (95% CI 9.6-12.1). Grade 3/4 neutropenia occurred in five
      patients, and two of these developed neutropenic fever. Grade 3 hematuria and
      hematochezia occurred in one. Grade 2 proteinuria occurred in two patients.
      However, hypertension, bowel perforation or thromboembolic events did not occur
      in a total of 90 cycles. CONCLUSION: Bevacizumab with FOLFIRI is well tolerated
      and a feasible treatment in patients with heavily treated advanced CRC.

PMID- 18069766
TI  - Predictive factors for interferon and ribavirin combination therapy in patients
      with chronic hepatitis C.
AB  - AIM: To confirm the predictive factors for interferon (IFN)-alpha and ribavirin
      combination therapy for chronic hepatitis patients with hepatitis C virus (HCV)
      genotype 1b. METHODS: HCV RNA from 50 patients infected with HCV genotype 1b was
      studied by cloning and sequencing of interferon sensitivity determining region
      (ISDR), PKR-eIF2alpha phosphorylation homology domain (PePHD). Patients were
      treated with IFN-alpha and ribavirin for 6 mo and grouped by effectiveness of the
      therapy. A variety of factors were analyzed. RESULTS: Our data showed that age,
      HCV RNA titer, and ISDR type could be used as the predictive factors for combined
      IFN-alpha and ribavirin efficacy. Characteristically, mutations in PePHD appeared
      only when the combination therapy was effective. Other factors, such as sex and
      alanine aminotransferase (ALT) level, were not related to its efficacy. Adjusting
      for age and HCV RNA titer indicated that the ISDR type was the most potent
      predictive factor. CONCLUSION: HCV RNA ISDR type is an important factor for
      predicting efficacy of IFN-alpha and ribavirin combination therapy in Korean
      patients.

PMID- 18069767
TI  - Effect and mechanism of beta-L-D4A on DNA polymerase alpha.
AB  - AIM: To investigate the safety of beta-L-D4A on DNA polymerase alpha. METHODS:
      Ion exchange chromatography was used to separate DNA polymerase alpha from crude
      extract of human Hela cells. Detailed kinetic parameters were determined for beta
      L-D4A against DNA polymerase alpha. RESULTS: DNA polymerase alpha was purified
      with 4% yield and 31000 units/mg specific activity. The Michaelis constant (Km =
      3.22 micromol/L), 50% inhibition concentration (IC50 = 178.49 micromol/L) and
      inhibition constant (Ki = 126 micromol/L) of beta-L-D4A were determined by
      kinetic analysis. CONCLUSION: beta-L-D4A is a more safe nucleoside for hepatitis
      B virus infection with a lower host toxicity.

PMID- 18069768
TI  - Effects of endogenous nitric oxide induced by 5-fluorouracil and L-Arg on liver
      carcinoma in nude mice.
AB  - AIM: To study the effects of endogeous nitric oxide induced by 5-fluorouracil (5
      FU) and L-arginine (L-Arg) on the human liver carcinoma model in nude mice.
      METHODS: The human liver carcinoma model in nude mice was established with BEL
      7402 cells and normal saline (NS), 5-FU and 5-FU + L-Arg injected
      intraperitoneally. The tumor size was measured. The necrotic degree and range
      were observed under microscope. The apoptosis of cancer cell was detected by
      turmina deoxynucleotidyl transferanse mediated dUTP nick end labeling (TUNEL)
      method. Immunohistochemical method was performed to determine the expression of
      iNOS, P16, BAX. The chemical colorimetry was used to test the activity and
      nitrate reductase method was adopted to test the concentration of nitric oxide
      (NO) in the tumor tissue. The BI2000 pathological image analyzer was used to
      analyze the result of immunohistochemistry. RESULTS: 5-FU combined with L-Arg
      could inhibit the tumor growth apparently. In NS, 5-FU and 5-FU+L-Arg groups, the
      changes of tumor volumes were 257.978 +/- 59.0, 172.232 +/- 66.0 and 91.523 +/-
      26.7 mm(3), respectively (P < 0.05 5-FU vs 5-FU + L-Arg group; P < 0.05 NS vs 5
      FU + L-Arg group; P < 0.05, NS vs 5-FU group). The necrotic range and apoptosis
      index were significantly increased after the drug injection. The necrotic range
      was biggest in 5-FU + L-Arg group (c2 = 15.963, P < 0.05). The apoptosis indexes
      were as follows: NS, 17.4% +/- 6.19%; 5-FU, 31.3% +/- 12.3%; and 5-FU + L-Arg,
      46% +/- 15.24% (P < 0.05, 5-FU vs 5-FU + L-Arg; P < 0.05, NS vs 5-FU + L-Arg; P <
      0.05, NS vs 5-FU). The expression and activity of iNOS were increased in the
      tumor tissue. The concentration of NO was also increased. F of optical density of
      iNOS, iNOS activity and NO concentration are 31.693, 21.949, and 33.909,
      respectively, P < 0.05. The concentration of NO was related to the expression of
      P16 and BAX. The correlation coefficient was 0.764 and 0.554. CONCLUSION: 5-FU
      combined with L-Arg can inhibit the growth of tumor in nude mice. The effect may
      be related to inducing the synthesis and increasing the activity of iNOS. The
      production of NO is increased, and it can enhance the expression of apoptosis
      related gene and antioncogene.

PMID- 18069769
TI  - Two novel germline mutations of MLH1 and investigation of their pathobiology in
      hereditary non-polyposis colorectal cancer families in China.
AB  - AIM: To detect germline mutations of MLH1, and investigate microsatellite
      instability and expression of MLH1 in tumor tissues of hereditary non-polyposis
      colorectal cancer (HNPCC) with two novel germline mutations, and further
      investigate the pathobiology of the two novel mutations of MLH1. METHODS: RNA was
      extracted from the peripheral blood of 12 patients from 12 different families
      that fulfilled the Amsterdam II Criteria for HNPCC. Germline mutations of MLH1
      were determined by RT-PCR, followed by cDNA sequencing analysis. PCR-GeneScan
      analysis was used to investigate microsatellite instability with a panel of five
      microsatellite markers (BAT26, BAT25, D5S346, D2S123 and mfd15), along with
      immunohistochemical staining to detect the expression of MLH1 protein in two
      patients' tumor tissues with novel mutations. RESULTS: Three germline mutations
      were found in four patients, one of the mutations has previously been reported,
      but the other two, CGC right arrow TGC at codon 217 of exon 8 and CCG right arrow
      CTG at codon 581 of exon 16, have not been reported. The two patients' tumor
      tissues with novel mutations had high-frequency microsatellite instability that
      showed more than two unstable loci, and both tumors lost their MLH1 protein
      expression. CONCLUSION: The two novel germline mutations of MLH1 in HNPCC
      families i.e. CGC right arrow TGC at codon 217 of exon 8 and CCG right arrow CTG
      at codon 581 of exon 16, are very likely to have pathological significance.

PMID- 18069770
TI  - Effects of short-term application of low-dose growth hormone on trace element
      metabolism and blood glucose in surgical patients.
AB  - AIM: To investigate the effects of short-term application of low-dose growth
      hormone on trace element metabolism and blood glucose in surgical patients.
      METHODS: A total of 48 consecutive patients undergoing abdominal operations were
      randomized to receive either subcutaneous rhGH (0.15 IU/kg) or placebo
      (menstruum) injections daily for 7 d after surgery. The two groups had similar
      nutrition intake. Blood, feces, urine and drain samples were collected to measure
      zincum, cuprum and ferrum as well as glucose levels. Accumulative intake,
      excretion and balance of zincum, cuprum and ferrum, apparent absorption (AA) and
      apparent utilization (AU) of zincum, cuprum and ferrum, blood glucose levels and
      adverse events were estimated. RESULTS: There were no differences in accumulative
      intake and drain excretion between the two groups. The feces excretion and
      accumulative excretion of cuprum were lower in the rhGH group (P < 0.05). The
      urinary excretion of zincum, cuprum and ferrum was all significantly decreased in
      the rhGH group (P < 0.05) and the accumulative balance of zincum, cuprum and
      ferrum was improved compared with the placebo group (P < 0.05). AA of cuprum in
      the rhGH group was almost twice as much as the placebo group (P < 0.05), and AU
      of zincum, cuprum and ferrum was all improved in the rhGH group (P < 0.05). The
      mean blood glucose level was significantly higher in the rhGH group than in the
      placebo group from d 3 to d 6 after operation (P < 0.05). CONCLUSION:
      Postoperative low-dose rhGH treatment improves the retention of zincum, cuprum
      and ferrum and decreases the excretion of zincum, cuprum and ferrum, improves the
      balance of zincum, cuprum and ferrum, and promotes the AA and AU of zincum,
      cuprum and ferrum. rhGH can be well tolerated without significant adverse effects
      and the blood glucose level can be well controlled.

PMID- 18069771
TI  - Relationship between survivin expression and recurrence, and prognosis in
      hepatocellular carcinoma.
AB  - AIM: To study the expression of the inhibitor of apoptosis protein survivin in
      hepatocellular carcinoma (HCC), and its correlation with clinicopathological
      factors, cell proliferation, recurrence and prognosis after hepatectomy. METHODS:
      Immunohistochemical staining of survivin and Ki-67 was performed by the standard
      streptavidin-peroxidase technique on paraffin sections of 55 cases of HCC.
      RESULTS: The positive rate of survivin in HCC was 52.7% (29/55). Significant
      correlation was found between survivin expression with portal vein thrombi and
      intrahepatic matastasistic nodes (P < 0.05). The recurrent rate in survivin
      positive HCC was significantly higher than that in survivin-negative HCC after
      hepatectomy, the 1- and 3-year survival rate in patients with survivin-positive
      tumors was significantly lower than that in patients with survivin-negative
      tumors (58.62 and 10.34% vs 76.92 and 30.77%, P < 0.05, log-rank test). The
      proliferation index (Ki-67) in survivin-positive HCC (33.83% +/- 18.90%) was
      significantly higher than that in survivin-negative HCC (19.60% +/- 19.35%) (P <
      0.05). CONCLUSION: Survivin may play an important role in progression of HCC by
      promoting cell proliferation, and may be positively correlated with high risk of
      disease recurrence and poor prognosis in HCC. Its expression may serve as a
      prognostic factor for patients with HCC after hepatectomy.

PMID- 18069772
TI  - Relationship between vascular invasion and microvessel density and
      micrometastasis.
AB  - AIM: To evaluate the relationship between vascular invasion and microvessel
      density (MVD) of tissue and micrometastasis in blood. METHODS: Vascular invasion
      was detected by both hematoxylin and eosin staining and immunohistochemiscal
      staining. Blood samples were collected from 17 patients with vascular invasion
      and 29 patients without vascular invasion and examined for cytokeratin20 (CK20)
      expression by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.
      Microvessel density of tissue samples was also determined by immunohistochemistry
      using antibodies to CD105. RESULTS: CK20 was detected in 12 of the 17 patients
      with vascular invasion and in 9 of the 29 patients without vascular invasion.
      Positive RT-PCR was significantly correlated with vascular invasion (70.6% vs
      30.0%, P < 0.05). The average MVD was significantly higher in patients with
      positive vascular invasion than in patients with negative vascular invasion (29.2
      +/- 3.3 vs 25.4 +/- 4.7, P < 0.05). The vascular invasion detected with
      hematoxylin-eosin staining was less than that with immunohistochemical staining.
      There was a significant difference between the two staining methods (19.6% vs
      36.9%, P < 0.05). CONCLUSION: Positive CK20 RT-PCR, depth of tumor invasion,
      lymph node status, metastasis and MVD are significantly correlated with vascular
      invasion. Immunohistochemical staining is more sensitive than hematoxylin-eosin
      staining for detecting vascular invasion.

PMID- 18069773
TI  - A phantom gallbladder on endoscopic retrograde cholangiopancreatography.
AB  - Various complications have been related to laparoscopic cholecystectomy but most
      occur shortly after the procedure. In this report, we present a case with very
      late complications in which an abscess developed within the gallbladder fossa 6
      years after laparoscopic cholecystectomy. The abscess resolved after treatment
      with CT-guided extrahepatic aspiration. However, 4 years later, an endoscopic
      retrograde cholangiopancreatography (ERCP) performed for choledocholithiasis
      demonstrated a "gallbladder" which communicated with the common bile duct via a
      patent cystic duct. This unique case indicates that a cystic duct stump may
      communicate with the gallbladder fossa many years following cholecystectomy.

PMID- 18069774
TI  - Prolonged cholestasis following successful removal of common bile duct stones:
      beware patients on estrogen therapy.
AB  - There are various well described forms of chronic cholestatic jaundice in adults,
      such as autoimmune cholangitis, drug-induced cholangitis and intrahepatic
      cholestasis of pregnancy. We present two cases of prolonged cholestasis following
      removal of gallstones at endoscopic retrograde cholangiopancreatography (ERCP)
      and subsequent clear cholangiography. Both patients were taking oral estrogens at
      the time of presentation, which were subsequently withdrawn. The first case
      responded rapidly to corticosteroid treatment, and the second case had a much
      slower resolution with ursodeoxycholic acid. Both cases highlighted the
      significance of estrogen-induced cholestasis in female patients with protracted
      jaundice following ERCP and removal of intra-ductal stones. After oral estrogens
      are discontinued, a short course of steroids needs to be considered.

PMID- 18069775
TI  - Penetrating ectopic peptic ulcer in the absence of Meckel's diverticulum
      ultimately presenting as small bowel obstruction.
AB  - We report here how a heterotopic penetrating peptic ulcer progressed to cause
      small bowel obstruction in a patient with multiple previous negative
      investigations. The clinical presentation, radiographic features and pathological
      findings of this case are described, along with the salient lessons learnt. The
      added value of wireless capsule endoscopy (WCE) in such circumstances is debated.

PMID- 18069776
TI  - Hepatic hydrothorax occurring rapidly after manual abdominal compression.
AB  - Hepatic hydrothorax is a relatively infrequent but potentially serious
      complication of liver cirrhosis that often causes respiratory dysfunction.
      Several hypotheses for the development of hepatic hydrothorax have been suggested
      to explain a transdiaphragmatic shift of ascitic fluid through small defects
      between the peritoneal cavity and the pleural space. However, the rapid
      development of hydrothorax within several hours is seldom encountered. In
      addition, the causal factors for rapid passage of ascitic fluid into the pleural
      cavity are unknown. This report describes a patient with liver cirrhosis who
      suffered rapid development of a hydrothorax after manual compression of the
      abdomen.

PMID- 18069777
TI  - Reversible pegylation prolongs the hypotensive effect of atrial natriuretic
      peptide.
AB  - Natriuretic peptides (NP), including atrial natriuretic peptide (ANP), induce
      potent natriuresis and vasodilation and thereby generate hypotension in vivo.
      Despite intensive efforts, clinical application of NP as an antihypertensive
      agent is limited because of their short biological half-life and poor
      bioavailability. Recently, we have developed a strategy that facilitates slow
      release of peptides from PEG-peptide inactive conjugates, based on reversible
      pegylation. Peptides prepared by this approach undergo slow, spontaneous chemical
      hydrolysis at physiological conditions, releasing the native active
      peptide/protein drug from the inactive conjugates over prolonged periods. A PEG
      chain of 30 kDa was linked covalently to the alpha-amino side chain of the
      hormone via a MAL-Fmoc-NHS spacer, yielding PEG 30-Fmoc-ANP, a prodrug that
      releases the native hormone upon incubation at physiological conditions. Bolus
      administration of native ANP to Wistar rats receiving adrenaline yields a short,
      transitory effect in lowering blood pressure (BP), reaching a maximum at 2 min,
      and then returning to control values after 12 to 25 min. In contrast,
      administration of PEG 30-Fmoc-ANP lowered BP following a lag period of 50 min,
      and maintained low BP for a period exceeding 60 min. Saline or PEG 30-Fmoc
      Alanine were not effective in lowering BP in Wistar rats. These results show that
      the novel compound, PEG 30-Fmoc-ANP, is a reversible pegylated prodrug derivative
      that facilitates a prolonged BP lowering effect in rats and may be considered as
      a candidate for development into an antihypertensive drug.

PMID- 18069779
TI  - Attachment of peptide building blocks to proteins through tyrosine
      bioconjugation.
AB  - Recent efforts have yielded a number of short peptide sequences with useful
      binding, sensing, and cellular uptake properties. In order to attach these
      sequences to tyrosine residues on intact proteins, a three-component Mannich-type
      strategy is reported. Two solid phase synthetic routes were developed to access
      peptides up to 20 residues in length with anilines at either the N- or C-termini.
      In the presence of 20 mM formaldehyde, these functional groups were coupled to
      tyrosine residues on proteins under mild reaction conditions. The identities of
      the resulting bioconjugates were confirmed using mass spectrometry and immunoblot
      analysis. Screening experiments have demonstrated that the method is compatible
      with substrates containing all of the amino acids, including lysine and cysteine
      residues. Importantly, tyrosine residues on proteins exhibit much faster reaction
      rates, allowing short peptides containing this residue to be coupled without
      cross reactions.

PMID- 18069778
TI  - Linker effects on biological properties of 111In-labeled DTPA conjugates of a
      cyclic RGDfK dimer.
AB  - In this report, we present in vitro and in vivo evaluation of three 111 In
      labeled DTPA conjugates of a cyclic RGDfK dimer: DTPA-Bn-SU016 (SU016 =
      E[c(RGDfK)] 2; DTPA-Bn = 2-( p-isothioureidobenzyl)diethylenetriaminepentaacetic
      acid), DTPA-Bn-E-SU016 ( E = glutamic acid) and DTPA-Bn-Cys-SU016 (Cys = cysteic
      acid). The integrin alpha vbeta 3 binding affinities of SU016, DTPA-Bn-SU016,
      DTPA-Bn-E-SU016, and DTPA-Bn-Cys-SU016 were determined to be 5.0 +/- 0.7 nM, 7.9
      +/- 0.6 nM, 5.8 +/- 0.6 nM, and 6.9 +/- 0.9 nM, respectively, against 125 I
      c(RGDyK) in binding to integrin alpha vbeta3, suggesting that E or Cys residue
      has little effect on the integrin alpha vbeta3 affinity of E[c(RGDfK)] 2. It was
      also found that the 111 In-labeling efficiency of DTPA-Bn-SU016 and DTPA-Bn-E
      SU016 is 3-5 times better than that of DOTA analogues due to fast chelation
      kinetics and high-yield 111 In-labeling under mild conditions (e.g., room
      temperature). Biodistribution studies were performed using BALB/c nude mice
      bearing U87MG human glioma xenografts. 111 In-DTPA-Bn-SU016, 111 In-DTPA-Bn-E
      SU016, and 111 In-DTPA-Bn-Cys-SU016 all displayed rapid blood clearance. Their
      tumor uptake was comparable between 0.5 and 4 h postinjection (p.i.) within
      experimental error. 111 In-DTPA-Bn-E-SU016 had a significantly lower ( p < 0.01)
      kidney uptake than 111 In-DTPA-Bn-SU016 and 111 In-DTPA-Bn-Cys-SU016. The liver
      uptake of 111 In-DTPA-Bn-SU016 was 1.69 +/- 0.18% ID/g at 24 h p.i., while the
      liver uptake values of 111 In-DTPA-Bn-E-SU016 and 111 In-DTPA-Bn-Cys-SU016 were
      0.55 +/- 0.11% ID/g and 0.79 +/- 0.15% ID/g at 24 h p.i., respectively. Among the
      three 111 In radiotracers evaluated in this study, 111 In-DTPA-Bn-E-SU016 has the
      lowest liver and kidney uptake and the best tumor/liver and tumor/kidney ratios.
      Results from metabolism studies indicated that there is little metabolism (<10%)
      for three 111 In radiotracers at 1 h p.i. Imaging data showed that tumors can be
      clearly visualized at 4 h p.i. with good contrast in the tumor-bearing mice
      administered with 111 In-DTPA-Bn-E-SU016. It is concluded that using a glutamic
      acid linker can significantly improve excretion kinetics of the 111 In-labeled
      E[c(RGDfK)] 2 from liver and kidneys.

PMID- 18069780
TI  - Molecular scale architecture: engineered three- and four-way junctions.
AB  - Biomolecular self-assembly provides a basis for the bottom-up construction of
      useful and diverse nanoscale architectures. DNA is commonly used to create these
      assemblies and is often exploited as a lattice or an array. Although
      geometrically rigid and highly predictable, these sheets of repetitive constructs
      often lack the ability to be enzymatically manipulated or elongated by standard
      biochemical techniques. Here, we describe two approaches for the construction of
      position-controlled, molecular-scale, discrete, three- and four-way DNA
      junctions. The first approach for constructing these junctions relies on the use
      of nonmigrating cruciforms generated from synthetic oligonucleotides to which
      large, biologically generated, double-stranded DNA segments are enzymatically
      ligated. The second approach utilitizes the DNA methyltransferase-based SMILing
      (sequence-specific methyltransferase-induced labeling of DNA) method to site
      specifically incorporate a biotin within biologically derived DNA. Streptavidin
      is then used to form junctions between unique DNA strands. The resultant
      assemblies have precise and predetermined connections with lengths that can be
      varied by enzymatic or hybridization techniques, or geometrically controlled with
      standard DNA functionalization methods. These junctions are positioned with
      single nucleotide resolution on large, micrometer-length templates. Both
      approaches generate DNA assemblies which are fully compatible with standard
      recombinant methods and thus provide a novel basis for nanoengineering
      applications.

PMID- 18069781
TI  - Layered inorganic/enzyme nanohybrids with selectivity and structural stability
      upon interacting with biomolecules.
AB  - Effective intercalation of protein molecules within the galleries of
      montmorillonites can be achieved via simple space enlarging and exchange
      processes while retaining the native conformation of the guest protein and the
      multilayered structure of the bioinert host plates. The capacity of accommodating
      protein molecules in the galleries can be markedly larger than that governed by
      the Langmuir-type adsorption of protein molecules on the external surfaces of
      particles. The basal spacing in the multilayered structure of clay is abruptly
      enlarged when the extent of protein intercalation increases to a critical point.
      Beyond this critical point, the nanohybrids show well-preserved catalytic
      activity in hydrolyzing small substrates while establishing a barrier to
      interactions with large biomacromolecules. Furthermore, the structural stability
      of the inorganic/organic nanohybrids is enhanced such that neither exchange of
      biomolecules nor exfoliation of layered clay particles occurs when exposed to
      other proteins. The results indicate that, through the benign accommodation of
      protein species between the inorganic platelets, this nanoscaled manipulation of
      protein functions can be highly useful in developing new inorganic/enzyme
      nanohybrids for protein therapeutics and tissue engineering.

PMID- 18069782
TI  - Immunochemical analysis of 2,4,6-tribromophenol for assessment of wood
      contamination.
AB  - 2,4,6-Tribromophenol (2,4,6-TBP) has been used as a wood preservative and flame
      retardant and is a synthetic intermediate of the most important brominated flame
      retardants (BFR) produced. The use of TBP-contaminated wood materials in the food
      industry poses a risk of significant economical losses due to food contamination.
      In this work an efficient and reliable immunochemical method for analysis of TBP
      in wood samples has been established consisting of alkaline wood extraction
      followed by analysis on a microplate ELISA (enzyme-linked immunosorbent assay).
      TBP is efficiently extracted from wood samples in 10 min and directly measured
      after 10-fold buffer dilution to avoid matrix interferences. The analytical
      procedure has a limit of detection of 45 ng g (-1) of TBP in wood (1.5 microg L (
      1) in extracts). The method has been applied to the analysis of contaminated real
      wood samples, showing that the levels of contamination can reach high TBP
      concentrations (up to 2000 microg L (-1)). An excellent correlation was observed
      between TBP levels in wood extracts determined by ELISA and gas chromatography
      mass spectrometry (GC-MS) analysis ( R (2) = 0.990, N = 19). The precision found
      is below 22% CV. The immunoanalytical method developed is fast, reliable, and
      cost-effective, shows good high-throughput screening capabilities, and can be an
      excellent tool for assessment of wood contamination at lumber mills or related
      industries. The TBP ELISA has the potential to be used for environmental, food,
      and biological monitoring of brominated phenolic compounds considered nowadays as
      emerging pollutants.

PMID- 18069783
TI  - Water solubility of flavor compounds influences formation of flavor inclusion
      complexes from dispersed high-amylose maize starch.
AB  - High-amylose maize starch, with and without native lipid, was used to make
      inclusion complexes with flavor compounds to investigate the effect of water
      solubility of flavor compounds on inclusion complex formation. Two pairs of
      terpenes, having high and low water solubility, were used. Aqueous starches were
      dispersed by heat before adding the flavor compound. The amounts of starch,
      native lipid, and flavor compound in precipitates were determined, and inferences
      about the physical state were made using data from X-ray diffraction and
      differential scanning calorimetry. The water solubility of the flavor compound
      was related to the extent of inclusion complexation. For the higher water
      solubility flavor compounds, starch yield and flavor entrapment were higher,
      producing precipitates with the V 7 pattern. Complex formation with the low
      solubility flavor compounds was most effective in the presence of native lipid,
      producing precipitates with the V 6 pattern. The lipid in native high-amylose
      maize starch may enhance complexation with low-solubility compounds by forming
      ternary coinclusion complexes of starch-lipid-flavor.

PMID- 18069784
TI  - Characterization and role of polyphenol oxidase and peroxidase in browning of
      fresh-cut melon.
AB  - Polyphenol oxidase (PPO) and peroxidase (POD) were extracted from two different
      varieties of melon ( Cucumis melo L. cantalupensis cv. Charentais and C. melo L.
      inodorus cv. Amarillo) and characterized using reliable spectrophotometric
      methods. In both cases the enzymes followed Michaelis-Menten kinetics, showing
      different values of kinetics parameters between the two cultivars: K m = 7.18 +/-
      0.70 mM ('Charentais') and 6.66 +/- 0.20 mM ('Amarillo') mM; V max = 7.93 +/-
      0.35 units/min ('Charentais') and 13.82 +/- 0.37 units/min ('Amarillo'), relative
      to PPO; K m = 24.0 +/- 2.10 mM ('Charentais') and 5.05 +/- 0.19 mM ('Amarillo')
      mM; V max = 344.83 +/- 10.32 units/min ('Charentais') and 80.64 +/- 2.01
      units/min ('Amarillo'), relative to POD. Optimum pH for PPO was 7.0 for
      'Charentais' and 7.5 for 'Amarillo, whereas it was 4.5 for both cultivars
      relative to POD. Melon PPO had maximum activity at 60 degrees C in both
      'Charentais' and 'Amarillo' cultivars, whereas POD maximum activity was found at
      45 degrees C in 'Charentais' and at 25 degrees C in 'Amarillo'. POD from both
      cultivars showed higher thermolability compared with PPO, losing >90% of relative
      activity after only 5 min of incubation at 70 degrees C. POD's activation energy
      was much higher than that of PPO (Delta E (#) = 86.3 and 160.6 kJ mol (-1) for
      'Charentais' and 'Amarillo', respectively). PPO and POD activities from both
      cultivars showed a decreasing pattern as sugar concentration in the assay medium
      increased, except in POD extract from 'Charentais', which maintained its activity
      in the presence of high d-glucose concentration (up to 5 M). Changes in L*, a*,
      b*, chroma, and hue angle values were chosen to describe the browning development
      in the samples during storage at 5 degrees C. A slight decrease in L* value and a
      more marked reduction of a* value were noted in both cultivars above all at the
      end of storage period. POD activity during storage at 5 degrees C was highly
      correlated with changes of parameters a*, b*, chroma, and hue angle ( r (2) from
      0.82 to 0.97) for cultivar 'Charentais'. According to these results, only POD
      activity seemed to be involved in browning of minimally processed melon.

PMID- 18069785
TI  - Effects of different cooking methods on nutritional and physicochemical
      characteristics of selected vegetables.
AB  - The objective of the present study was to evaluate the effect of three common
      cooking practices (i.e., boiling, steaming, and frying) on phytochemical contents
      (i.e., polyphenols, carotenoids, glucosinolates, and ascorbic acid), total
      antioxidant capacities (TAC), as measured by three different analytical assays
      [Trolox equivalent antioxidant capacity (TEAC), total radical-trapping
      antioxidant parameter (TRAP), ferric reducing antioxidant power (FRAP)] and
      physicochemical parameters of three vegetables (carrots, courgettes, and
      broccoli). Water-cooking treatments better preserved the antioxidant compounds,
      particularly carotenoids, in all vegetables analyzed and ascorbic acid in carrots
      and courgettes. Steamed vegetables maintained a better texture quality than
      boiled ones, whereas boiled vegetables showed limited discoloration. Fried
      vegetables showed the lowest degree of softening, even though antioxidant
      compounds were less retained. An overall increase of TEAC, FRAP, and TRAP values
      was observed in all cooked vegetables, probably because of matrix softening and
      increased extractability of compounds, which could be partially converted into
      more antioxidant chemical species. Our findings defy the notion that processed
      vegetables offer lower nutritional quality and also suggest that for each
      vegetable a cooking method would be preferred to preserve the nutritional and
      physicochemical qualities.

PMID- 18069786
TI  - Quantitation of 13 heterocyclic aromatic amines in cooked beef, pork, and chicken
      by liquid chromatography-electrospray ionization/tandem mass spectrometry.
AB  - The concentrations of heterocyclic aromatic amines (HAAs) were determined, by
      liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI
      MS/MS), in 26 samples of beef, pork, and chicken cooked to various levels of
      doneness. The HAAs identified were 2-amino-3-methylimidazo[4,5- f]quinoline, 2
      amino-1-methylimidazo[4,5- b]quinoline, 2-amino-1-methylimidazo[4,5-
      g]quinoxaline (I gQx), 2-amino-3-methylimidazo[4,5- f]quinoxaline, 2-amino-1,7
      dimethylimidazo[4,5- g]quinoxaline (7-MeI gQx), 2-amino-3,8-dimethylimidazo[4,5-
      f]quinoxaline, 2-amino-1,6-dimethyl-furo[3,2- e]imidazo[4,5- b]pyridine, 2-amino
      1,6,7-trimethylimidazo[4,5- g]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5-
      f]quinoxaline, 2-amino-1,7,9-trimethylimidazo[4,5- g]quinoxaline, 2-amino-1
      methyl-6-phenylimidazo[4,5- b]pyridine (PhIP), 2-amino-9 H-pyrido[2,3- b]indole,
      and 2-amino-3-methyl-9 H-pyrido[2,3- b]indole. The concentrations of these
      compounds ranged from <0.03 to 305 parts per billion (micrograms per kilogram).
      PhIP was the most abundant HAA formed in very well done barbecued chicken (up to
      305 microg/kg), broiled bacon (16 microg/kg), and pan-fried bacon (4.9
      microg/kg). 7-MeI gQx was the most abundant HAA formed in very well done pan
      fried beef and steak, and in beef gravy, at concentrations up to 30 microg/kg.
      Several other linear tricyclic ring HAAs containing the I gQx skeleton are formed
      at concentrations in cooked meats that are relatively high in comparison to the
      concentrations of their angular tricyclic ring isomers, the latter of which are
      known experimental animal carcinogens and potential human carcinogens. The
      toxicological properties of these recently discovered I gQx derivatives warrant
      further investigation and assessment.

PMID- 18069787
TI  - Three polyphenol oxidases from red clover (Trifolium pratense) differ in
      enzymatic activities and activation properties.
AB  - Polyphenol oxidases (PPOs) oxidize o-diphenols to o-quinones, which cause
      browning reactions in many wounded fruits, vegetables, and plants including the
      forage crop red clover (Trifolium pratense L.). Production of o-quinones in red
      clover inhibits postharvest proteolysis during the ensiling process. The cDNAs
      encoding three red clover PPOs were expressed individually in alfalfa (Medicago
      sativa L.), which lacks detectable endogenous foliar PPO activity and o
      diphenols. Several physical and biochemical characteristics of the red clover
      PPOs in alfalfa extracts were determined. In transgenic alfalfa extracts, red
      clover PPOs exist in a latent state and are activated (10-40-fold increase in
      activity) by long incubations (>2 days) at ambient temperature or short
      incubations (<10 min) at > or =65 degrees C. PPO1 appears to be more stable at
      high temperatures than PPO2 or PPO3. During incubation at ambient temperature,
      the molecular masses of the PPO enzymes were reduced by approximately 20 kDa. The
      apparent pH optima of latent PPO1, PPO2, and PPO3 are 5.5, 6.9, and 5.1,
      respectively, and latent PPO1 is slightly activated (~5-fold) by low pH.
      Activation of the PPOs shifts the pH optima to approximately 7, and the activated
      PPOs retain substantial levels of activity as the pH increases above their
      optima. The latent and activated PPOs were surveyed for ability to oxidize
      various o-diphenols, and activation of the PPOs had little effect on substrate
      specificity. Activation increases the V max but not the affinity of the PPO
      enzymes for caffeic acid. Results indicate red clover PPOs undergo structural and
      kinetic changes during activation and provide new insights to their effects in
      postharvest physiology.

PMID- 18069788
TI  - Cloning, expression, and characterization of two beta-glucosidases from
      isoflavone glycoside-hydrolyzing Bacillus subtilis natto.
AB  - On the basis of the genomic sequence of Bacillus subtilis 168, two beta
      glucosidase genes (bglH and yckE) from B. subtilis natto, which has been reported
      to have high isoflavone glucoside-hydrolyzing activity, were cloned and
      overexpressed in E. coli M15. The temperature for the optimal p-nitrophenyl-beta
      D-glucoside hydrolyzing activity of both enzymes was between 37 and 45 degrees C,
      but BglH had a higher thermal stability than YckE. Both showed high activity at
      pH 6.0, but YckE was stable over a wider pH range than BglH. Recombinant BglH was
      inhibited 73%, 63%, and 43% by 1.0 mM Cd(2+), Fe(2+), or Cu(2+), respectively,
      while other divalent metal ions resulted in 0-23% inhibition, whereas YckE was
      inhibited by less than 20% by any of the divalent metal ions we tested. Among the
      substrate we used, BglH showed the highest affinity for genistin and YckE showed
      the highest affinity for p-nitrophenyl-beta-D-fructopyranoside. Both BglH and
      YckE hydrolyzed genistin and daidzin into their isoflavone aglycones, genistein
      and daidzein, but BglH was more efficient than YckE in isoflavone glucoside
      hydrolysis (20-fold higher kcat). Our results suggest that recombinant BglH may
      be applicable in the process of isoflavones deglycosylation.

PMID- 18069789
TI  - Field trapping of the invasive brown marmorated stink bug, Halyomorpha halys,
      with geometric isomers of methyl 2,4,6-decatrienoate.
AB  - The brown marmorated stink bug, Halyomorpha halys (Stal), is a polyphagous pest
      indigenous to northeastern Asia where it damages various trees, vegetables, and
      leguminous crops. The bug was recently introduced into the U.S. and could
      potentially become a pest. In its native range, H. halys was reportedly attracted
      to the aggregation pheromone of the brown-winged green bug, Plautia stali, methyl
      (2 E,4 E,6 Z)-decatrienoate. We also observed that traps baited with this
      compound are attractive to H. halys. We additionally found that methyl (2 E,4 E,6
      Z)-decatrienoate (as well as other isomeric methyl 2,4,6-decatrienoates) exposed
      to daylight in solutions and/or on dispensers used for field trapping can readily
      isomerize to form complex mixtures of isomers, thus causing a concern about lure
      stability and longevity. However, our studies demonstrated that preventing
      isomerization of methyl (2 E,4 E,6 Z)-decatrienoate in dispensers was not
      essential for field trapping of H. halys males, females, and nymphs. We also
      present evidence that traps baited with methyl (2 Z,4 E,6 Z)-decatrienoate and
      methyl (2 E,4 Z,6 Z)-decatrienoate (pheromone of Thyanta spp. pentatomids), as
      well as the mixtures of geometric isomers, attract H. halys. The ZEZ isomer,
      unknown in nature, as well as the EEZ isomer, elicited electrophysiological
      responses from antennae of H. halys males. The field data suggest that the
      presence of the EEZ but not ZEZ isomer in the lure is essential for attraction of
      H. halys, and that other isomers are not antagonistic and may even be needed for
      maximum attraction. Because the pheromone of H. halys is unknown at present,
      lures containing methyl (2 E,4 E,6 Z)-decatrienoate without protection from
      daylight are suitable for monitoring populations of H. halys late in the season.

PMID- 18069790
TI  - Kinetic studies of the free radical-scavenging actions of tocopherol metabolites
      (alpha-, gamma-, and delta-carboxyethyl-6-hydroxychroman) and Trolox in ethanol
      and micellar solutions.
AB  - The reaction rates ( k s) of tocopherol metabolites (alpha-, gamma-, and delta
      CEHC) and Trolox with aroxyl radical have been measured in ethanol and micellar
      solution by a stopped-flow spectrophotometer, and the k s values obtained were
      compared with those reported for tocopherols (alpha-, beta-, gamma-, and delta
      tocopherol, TocH) and tocol. The rate constants ( k s) increased in the order of
      Tocol < delta-CEHC < delta-TocH < gamma-CEHC < Trolox approximately gamma-TocH
      approximately beta-TocH < alpha-CEHC < alpha-TocH in ethanol. The antioxidants
      that have lower oxidation potentials ( E p) showed higher reactivities. The k s
      values of alpha-, beta-, gamma-, and delta-tocopherol and tocol in micelle
      remained constant between pH 4 and pH 10 and decreased rapidly at pH 11~12 by
      increasing pH value. On the other hand, the k s values of alpha-CEHC, gamma-CEHC,
      and Trolox showed notable pH dependence. As a result of the detailed analysis of
      the pH dependence of the rate constants ( k s), the structure-activity
      relationship in the free radical-scavenging action of the tocopherol metabolites
      and Trolox has been clarified.

PMID- 18069791
TI  - On the diffusion constant of water in wheat.
AB  - Diffusion-weighted magnetic resonance imaging (MRI) was used to obtain diffusion
      constants for water in the embryo and endosperm of wheat. Our experiments showed
      a significant difference between the diffusion constant for the two components.
      It was also shown that water diffusion in both the endosperm and embryo deviates
      from the typically observed Gaussian behavior in bulk fluids, showing a time
      dependent diffusion constant. Diffusion constants for the embryo and endosperm
      were shown to differ by an order of magnitude. Using a model for restricted
      diffusion, information on the endosperm pore size and the embryo cell dimensions
      could be obtained.

PMID- 18069792
TI  - Development of a dot blot assay for the rapid detection of central nervous system
      tissue on meat and contact surfaces.
AB  - As a potential transmitter of bovine spongiform encephalopathy (BSE), tissue from
      bovine central nervous system (CNS) is not accepted in meat and meat products.
      Western blot analysis of the CNS marker myelin proteolipid protein (PLP) detects
      CNS contamination selectively and sensitively. In this study, a rapid dot blot
      assay using an anti-PLP antibody was developed to screen CNS contamination of
      meat and contact surfaces. The detection limit was 0.01% bovine brain in minced
      bovine muscle. When applied to a swab test, down to 0.5 mg of CNS tissue on meat
      or other surfaces was detectable. Other offal tissues or peripheral nerves did
      not interfere with the assay. The test allows a differentiation between mammalian
      and avian CNS but not among mammalian species. The swab test was applied
      immediately after slaughtering at several areas of the bovine head. CNS was not
      detectable at any region which may enter the food chain.

PMID- 18069793
TI  - Encapsulation of quercetin and myricetin in cyclodextrins at acidic pH.
AB  - The in vitro formation of quercetin- and myricetin-cyclodextrin inclusion
      complexes in acidic medium has been characterized using the enzymatic system
      horseradish peroxidase, which oxidizes those flavonols in the presence of H2O2.
      The presence of cyclodextrins (CDs) in the reaction medium inhibited flavonol
      oxidation due to the complexation of the flavonol in the hydrophobic cavity of
      CDs. This inhibitory effect depends on the complexation constant Kc between
      flavonol and the CD type used. The Kc for quercetin and myricetin with the
      different types of CD used was calculated by nonlinear regression of the
      inhibition curves obtained in the presence of CDs. In both cases (quercetin and
      myricetin), the Kc values obtained followed the order hydroxypropyl-beta-CDs >
      maltosyl-beta-CDs > beta-CDs, reflecting the greater affinity of modified
      cyclodextrins for the studied flavonols compared with their parental beta-CDs.
      Moreover, the complexation efficiency (CE) values for HP-beta-CDs and quercetin
      or myricetin were calculated (267.4 and 5.3, respectively), indicating that HP
      beta-CDs are more efficient for the complexation of quercetin than myricetin in
      the studied conditions, despite of the K c values being very similar in both
      cases.

PMID- 18069794
TI  - Performance characteristics of countercurrent separation in analysis of natural
      products of agricultural significance.
AB  - A standard test mix consisting of 21 commercially available natural products of
      agricultural significance, termed the GUESSmix, was employed to measure the
      countercurrent chromatography performance characteristics of a very popular
      quaternary solvent system family made up of hexane-ethyl acetate-methanol-water
      (HEMWat). The polarity range of the GUESSmix combined with the elution-extrusion
      countercurrent chromatography (EECCC) technique and the newly developed
      reciprocal symmetry (ReS) and reciprocal shifted symmetry (ReSS) plots allow
      liquid-liquid distribution ratios ( K D) to be plotted for every compound eluted
      on a scale of zero to infinity. It was demonstrated that 16 of the 21 GUESSmix
      compounds are found in the optimal range of resolution (0.25 < K(D) < 16) of at
      least one HEMWat solvent system. The HEMWat solvent systems represented by the
      ratios 4:6:5:5, 4:6:4:6, and 3:7:4:6 possess the most densely populated optimal
      ranges of resolution for this standard mix. ReS plots have been shown to reveal
      the symmetrical reversibility of the EECCC method in reference to K(D) = 1. This
      study lays the groundwork for evaluation and comparison of solvent system
      families proposed in the literature, as well as the creation of new solvent
      system families with desired performance characteristics.

PMID- 18069795
TI  - Effect of 5-O-Methylhirsutanonol on nuclear factor-kappaB-dependent production of
      NO and expression of iNOS in lipopolysaccharide-induced RAW264.7 cells.
AB  - Diarylheptanoids are known to have anti-inflammatory and anti-atherosclerotic
      activities in various cell types, including macrophages. 5- O-Methylhirsutanonol
      (5-MH) isolated from the leaves of Alnus japonica Steud exhibited the antioxidant
      activities on Cu (2+)- and AAPH-mediated low-density lipoprotein (LDL) oxidation
      in the thiobarbituric acid-reactive substances (TBARS) assay as well as the
      macrophage-mediated LDL oxidation. In the main study, we examined anti
      inflammatory activities of 5- O-methylhirsutanonol (5-MH) on nuclear factor
      kappaB (NF-kappaB)-dependent nitric oxide (NO) production and expression of
      inducible nitric oxide synthease (iNOS) in lipopolysaccharide (LPS)-induced
      RAW264.7 macrophages. 5-MH inhibited NO production with an IC 50 value of 14.5
      microM and expression of both iNOS protein and iNOS mRNA in a parallel dose
      response manner. Then, expression of inflammation-associated genes, such as TNF
      alpha, COX-2, and IL-1beta, was suppressed by 5-MH, as determined by reverse
      transcriptase polymerase chain reaction analysis. Moreover, 5-MH attenuated NF
      kappaB activation by inhibition of hyperphosphorylation of IkappaB-alpha and its
      subsequent proteolytic degradation and p65 nuclear translocation, as well as
      preventing DNA-binding ability. In addition, 5-MH suppressed the mRNA expression
      of the gene reactive oxygen species (ROS) concerned in the regulation of NF
      kappaB signaling.

PMID- 18069796
TI  - Residual patterns of alkyl polyoxyethylene surfactant droplets after water
      evaporation.
AB  - Using a nonionic, alkyl polyoxyethylene surfactant (X-77) in aqueous solutions,
      sessile droplet spreading, pinning, evaporation, contraction, and post
      evaporation deposits are characterized. X-77 is widely used in the agricultural
      field as a spreader/adherent, intended to optimize pathenogenic agent coverage.
      Using a single droplet size under monitored temperature conditions, we control
      humidity, substrate hydrophobicity, and surfactant concentration to mimic varying
      agricultural conditions. For hydrophilic surfaces, the droplet spreads, reaching
      and retaining a maximum, stationary size. At this stage, a ring accretion occurs
      at the maximum spread diameter. During the final stage, the water film retracts,
      resulting in deposition of small islands of surfactant residue inside the ring.
      At lower concentrations of surfactant, we discover ring formations that break-up
      into "ring islands" at late-stage evaporation, accompanied by a distribution of
      the smaller islands in the interior portion of the substrate contact area. These
      are promoted by higher relative humidity. At higher concentrations, only a solid
      ring of surfactant remains, post-evaporation. Increasing surfactant concentration
      tends to increase the mean of the interior island size and to broaden the overall
      island size distribution. On sufficiently hydrophobic surfaces, surfactant-laden
      droplets do not evidence pinning, ring formations, or post-evaporation interior
      islands. Interestingly, lower humidity increases spreading at higher surfactant
      concentrations. Such pattern formations of surfactant deposit are reported for
      the first time and are of significance in projecting how surfactants such as X-77
      distribute pesticides or other chemicals on leaf surfaces.

PMID- 18069797
TI  - Role of the head-to-tail overlap region in smooth and skeletal muscle beta
      tropomyosin.
AB  - Tropomyosin (Tm) is an alpha-helical, parallel, two-chain coiled coil which binds
      along the length of actin filaments in both muscle and non-muscle cells. Smooth
      and skeletal muscle Tms differ extensively at the C-terminus encoded by exon 9.
      Replacement of the striated muscle specific exon 9a-encoded C-terminus with that
      encoded by exon 9d expressed in smooth muscle and non-muscle cells increases the
      affinity of unacetylated alpha-SkTm for actin [Cho, Y. J., and Hitchcock
      Degregori, S. E. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 10153-10157]. Here we
      show that swapping 10 amino acids at the C-terminus of beta-SkTm with the
      corresponding 10 amino acids of beta-SmTm had little effect on the regulation of
      S1 binding to actin, but Tm viscosity, Tm binding to actin, and troponin T1
      binding to Tm all become like smooth rather than SkTm. beta-SkTm point mutations
      show that these properties are largely defined by the amino acids at two
      positions, 277 and 279. The N279L mutation reduces the viscosity of beta-SkTm to
      close to beta-SmTm values, while both residues contribute to the binding of TnT1.
      We also show that removing the first 11 N-terminal amino acids of beta-SmTm to
      make the mutant DeltaN-betaSmTm results in a 10-fold weakening in actin affinity
      compared to that of beta-SmTm. CD studies show no difference in thermal unfolding
      between beta-SmTm and DeltaN-betaSmTm; however, the viscosity of DeltaN-betaSmTm
      is much lower than that of the control. The results suggest that DeltaN-betaSmTm
      was unable to form filaments in solution but can form filaments on actin.

PMID- 18069798
TI  - Crystal structure and function of 5-formaminoimidazole-4-carboxamide
      ribonucleotide synthetase from Methanocaldococcus jannaschii.
AB  - Purine biosynthesis requires 10 enzymatic steps in higher organisms, while
      prokaryotes require an additional enzyme for step 6. In most organisms steps 9
      and 10 are catalyzed by the purH gene product, a bifunctional enzyme with both 5
      formaminoimidazole-4-carboxamide ribonucleotide (FAICAR) synthase and inosine
      monophosphate (IMP) cyclohydrolase activity. Recently it was discovered that
      Archaea utilize different enzymes to catalyze steps 9 and 10. An ATP-dependent
      FAICAR synthetase is encoded by the purP gene, and IMP cyclohydrolase is encoded
      by the purO gene. We have determined the X-ray crystal structures of FAICAR
      synthetase from Methanocaldococcus jannaschii complexed with various ligands,
      including the tertiary substrate complex and product complex. The enzyme belongs
      to the ATP grasp superfamily and is predicted to use a formyl phosphate
      intermediate formed by an ATP-dependent phosphorylation. In addition, we have
      determined the structures of a PurP orthologue from Pyrococcus furiosus, which is
      functionally unclassified, in three crystal forms. With approximately 50%
      sequence identity, P. furiosus PurP is structurally homologous to M. jannaschii
      PurP. A phylogenetic analysis was performed to explore the possible role of this
      functionally unclassified PurP.

PMID- 18069799
TI  - Crystal structure of E47-NeuroD1/beta2 bHLH domain-DNA complex: heterodimer
      selectivity and DNA recognition.
AB  - The ubiquitous class I basic helix-loop-helix (bHLH) factor E47 forms
      heterodimers with multiple tissue specific class II bHLH proteins to regulate
      distinct differentiation pathways. In order to define how class I- class II
      heterodimer partners are selected, we determined the crystal structure of the E47
      NeuroD1-bHLH dimer in complex with the insulin promoter E-box sequence.
      Purification of the bHLH domain of E47-NeuroD1 indicates that E47 heterodimers
      are stable in solution. The interactions between E47 and NeuroD1 in the
      heterodimer are comparable to the interactions between E47 monomers in the
      homodimer, including hydrogen bonding, buried hydrophobic surface, and packing
      interactions. This is consistent with a model in which E47-NeuroD1 heterodimers
      are favored due to the instability of NeuroD1 homodimers. Although E47-NeuroD1 is
      oriented uniquely on the E-box sequence (CATCTG) within the promoter of the
      insulin gene, no direct contacts are observed with the central base pairs within
      this E-box sequence. We propose that concerted domain motions allow E47 to form
      specific base contacts in solution. NeuroD1 is restrained from adopting the same
      base contacts by an additional phosphate backbone interaction by the neurogenic
      specific residue His115. Orienting E47-NeuroD1 on promoters may foster protein
      protein contacts essential to initiate transcription.

PMID- 18069801
TI  - Structures of aliphatic amino acid proton-bound dimers by infrared multiple
      photon dissociation spectroscopy in the 700-2,000 cm(-1) region.
AB  - Structural aspects of proton-bound dimers composed of amino acids with aliphatic
      side chains are investigated using infrared multiple photon dissociation (IRMPD)
      spectroscopy and electronic structure calculations. Features in the IRMPD spectra
      in the 700-2,000 cm-1 range are due primarily to C=O stretching, NH2 bending, and
      COH bending. It was possible to distinguish between isomeric structures by
      comparing the experimental IRMPD spectra and those predicted using B3LYP/6
      31+G(d,p). It was possible, based on the calculations and IRMPD spectra, to
      assign the experimental spectrum of the glycine proton-bound dimer to a structure
      which was slightly different from that assigned by previous spectroscopic
      investigations and in agreement with recent thermochemical studies. Since all
      proton-bound dimers studied here, composed of the different amino acids, have
      very similar spectra, it is expected that they also have very similar lowest
      energy structures including the mixed alanine/glycine proton-bound dimer. In
      fact, the spectra are so similar that it would be very challenging to
      distinguish, for example, the glycine proton-bound dimer from the alanine or
      valine proton-bound dimers in the 700-2,000 cm-1 range. According to the
      calculated IR spectra it is shown that in the approximately 2,000-3,200 cm-1
      range differentiating between different structures as well as different proton
      bound dimers may be possible. This is due mainly to differences in the asymmetric
      stretch of the binding proton which is predicted to occur in this region.

PMID- 18069802
TI  - Theoretical study on the relationship between spin multiplicity effects and
      nonlinear optical properties of the pyrrole radical (C4H4N.).
AB  - The geometrical structure and stability of neutral pi-conjugated C4H4N. with
      three spin states were investigated by using ab initio and density functional
      theory (DFT) methods. In addition, the linear and nonlinear optical properties
      were studied at the same level combined with the finite field approach. The
      calculated results show that conjugation and stability decreased with increasing
      spin multiplicity. These reliable UCCSD results show that the polarizability
      (alpha) values of C4H4N. with the quartet state are maximal, while those of
      C4H4N. with the doublet state are minimal. The order of betatot values is
      betasextet > betadoublet > betaquartet. The second hyperpolarizability (gamma)
      values exhibit positive values. The variation trends of gamma are consistent with
      alpha.

PMID- 18069800
TI  - 4-Hydroxynonenal self-limits fas-mediated DISC-independent apoptosis by promoting
      export of Daxx from the nucleus to the cytosol and its binding to Fas.
AB  - Previously, we have shown that 4-hydroxynonenal (4-HNE) induces Fas-mediated
      apoptosis in HLE B-3 cells through a pathway which is independent of FasL, FADD,
      procaspase 8, and DISC (Li, J., et al. (2006) Biochemistry 45, 12253-12264). The
      involvement of Daxx has also been suggested in this pathway, but its role is not
      clear. Here, we report that Daxx plays an important regulatory role during 4-HNE
      induced, Fas-mediated apoptosis in Jurkat cells. 4-HNE induces Fas-dependent
      apoptosis in procaspase 8-deficient Jurkat cells via the activation of ASK1, JNK,
      and caspase 3, and the apoptosis can be inhibited by masking Fas with the
      antagonistic anti-Fas antibodies. We demonstrate that 4-HNE exposure to Jurkat
      cells leads to the induction of both Fas and Daxx. 4-HNE binds to both Fas and
      Daxx and promotes the export of Daxx from the nucleus to the cytosol, where it
      binds to Fas and inhibits apoptosis. Depletion of Daxx results in an increase in
      the activation of ASK1, JNK, and caspase 3 along with exacerbation of 4-HNE
      induced apoptosis, suggesting that Daxx inhibits apoptosis by binding to Fas. 4
      HNE-induced translocation of Daxx is also accompanied by the activation of the
      transcription factor HSF1. The results of these studies are consistent with a
      model in which, by interacting with Fas, 4-HNE promotes proapoptotic signaling
      via ASK1, JNK, and caspase 3. In parallel, 4-HNE induces Daxx and promotes its
      export from the nucleus to the cytosol, where it interacts with Fas to self-limit
      the extent of apoptosis by inhibiting the downstream proapoptotic signaling.
      Cytoplasmic translocation of Daxx also results in up-regulation of HSF1
      associated stress-responsive genes.

PMID- 18069803
TI  - A quantum chemistry study of the Cl atom reaction with formaldehyde.
AB  - The elementary vapor-phase reaction between Cl atoms and HCHO has been studied by
      ab initio methods. Calculations at the MP2, MP3, MP4(SDTQ), CCSD, CCSD(T), and
      MRD-CI levels of theory show that the reaction is characterized by a low
      electronic barrier; excluding the effects of spin-orbit splitting in Cl, our best
      estimate at the MRD-CI/aug-cc-pVTZ//RHF-RCCSD(T)/aug-cc-pVTZ level of theory
      predicts a Born-Oppenheimer barrier height of 0.7 kJ mol-1. The energies of the
      lowest six electronic states as resulting from MRD-CI calculations are presented
      at discrete points along the reaction path, and two avoided crossings are found
      in the transition state region. The spin-orbit splitting in Cl is also calculated
      along the reaction path; it is not negligible in the transition state region and
      is found to increase the barrier by only 1.4 kJ mol-1 at the RCCSD(T)/aug-cc-pVTZ
      transition state geometry. The minimum energy path of the reaction connects an
      energetically weakly stabilized adduct on the flat potential surface on the
      reactant side and an energetically strongly stabilized postreaction adduct. The
      reaction rate coefficient and the kinetic isotope effects were calculated using
      improved canonical variational theory with small curvature tunneling (ICVT/SCT),
      and the results were compared to experimental data. The experimental reaction
      rate coefficient is reproduced within its uncertainty limits by variational
      transition state theory with interpolated single-point energy corrections (ISPE)
      at the MP4(SDTQ) level of theory and by conventional transition state theory with
      interpolated optimized energies (IOE) at the MRD-CI//RCCSD(T) level of theory and
      interpolated optimized geometries at the RCCSD(T) level of theory on an MP2/aug
      cc-pVTZ potential energy surface when employing scaled vibrational frequencies.

PMID- 18069804
TI  - Theoretical study of the enthalpies of formation for C40H56 carotenes.
AB  - Theoretical study of the enthalpies of formation (DeltaHf) for polyenes up to
      nine ethylene units and for several C40H56 carotenes including beta-carotene,
      alpha-carotene, lycopene, and prolycopene is presented. For polyenes and small
      branched alkenes, we used G2, G3, and G3MP2B3 theories, and the DeltaHf values
      were evaluated with the atomization, isodesmic bond separation, and homodesmic
      schemes. The applicability of six DFT functionals were evaluated by comparing
      their predictions with those obtained using G3 theory within the atomization
      scheme. Additivity approaches, including atom equivalents and group equivalents
      using DFT and semiempirical theories, were explored. We found that group
      equivalents associated with isodesmic reactions are able to provide the most
      accurate predictions within the test set. The predictions from the six
      functionals are in good agreement with the G3 results. Among them, B3LYP performs
      the best, with an average absolute deviation of only 0.30 kcal/mol. The
      application of DFT in the prediction for the DeltaHf value of C40H56 carotenes is
      promising.

PMID- 18069805
TI  - Molecular structure, vibrational spectra, quantum chemical calculations and
      photochemistry of picolinamide and isonicotinamide isolated in cryogenic inert
      matrixes and in the neat low-temperature solid phases.
AB  - Picolinamide (PA) and isonicotinamide (INA), two structural isomers of
      pyridinecarboxamide, have been investigated by matrix isolation and low
      temperature solid-state infrared spectroscopy, combined with UV (lambda > 235 nm)
      photoexcitation and density functional theory and ab initio (MP2) theoretical
      studies. In consonance with the theoretical data, both PA and INA were found to
      exist in a single conformation in cryogenic rare gas matrixes. Comparison between
      the experimental spectra of the matrix-isolated compounds with those
      theoretically predicted allowed for full assignment of the experimental spectra.
      In situ UV (lambda > 235 nm) irradiation of the matrixes showed that only PA
      reacts, with production of isocyanic acid and pyridine, the first photoproduct
      further reacting to yield CO + NH and cyanic acid. The different photochemical
      behavior of the two compounds was explained taking into consideration their
      different structures. The infrared spectra of (i) the low-temperature glassy
      state resulting from fast deposition of vapors of the compounds onto a substrate
      cooled to 10 K, (ii) the crystal resulting from the annealed amorphous film of
      the compound, and (iii) the room-temperature crystals (alpha-phase) of the
      studied compounds were also obtained, fully assigned and correlated with
      intermolecular interactions present in the condensed phases, in particular H-bond
      interactions, showing that these latter are stronger in INA than in PA.

PMID- 18069806
TI  - Linear C(n) clusters: are they acetylenic or cumulenic?
AB  - Uncapped linear Cn clusters have been studied with hybrid density functional
      theory focusing on the geometry, HOMO-LUMO gap, and the longitudinal optical (LO)
      vibrational mode. The latter two correlate well with the bond length alternation
      (BLA) of the optimized geometry. Due to end effects, the BLA is not constant
      along the chains. The degree of BLA changes continuously with increasing n:
      starting with essentially nonalternating structures (cumulenic), then turning
      into strongly alternating (acetylenic) structures. This transition has not yet
      been described or characterized and occurs at relatively large values of n. The
      implications for the widely observed characteristic LO vibrational bands of
      linear carbon clusters are discussed.

PMID- 18069807
TI  - Addition reaction of adamantylideneadamantane with Br2 and 2Br2: a computational
      study.
AB  - Ab initio calculations were carried out for the reaction of
      adamantylideneadamantane (Ad=Ad) with Br2 and 2Br2. Geometries of the reactants,
      transition states, intermediates, and products were optimized at HF and B3LYP
      levels of theory using the 6-31G(d) basis set. Energies were also obtained using
      single point calculations at the MP2/6-31G(d)//HF/6-31G(d), MP2/6-31G(d)//B3LYP/6
      31G(d), and B3LYP/6-31+G(d)//B3LYP/6-31G(d) levels of theory. Intrinsic reaction
      coordinate (IRC) calculations were performed to characterize the transition
      states on the potential energy surface. Only one pathway was found for the
      reaction of Ad=Ad with one Br2 producing a bromonium/bromide ion pair. Three
      mechanisms for the reaction of Ad=Ad with 2Br2 were found, leading to three
      different structural forms of the bromonium/Br3- ion pair. Activation energies,
      free energies, and enthalpies of activation along with the relative stability of
      products for each reaction pathway were calculated. The reaction of Ad=Ad with
      2Br2 was strongly favored over the reaction with only one Br2. According to
      B3LYP/6-31G(d) and single point calculations at MP2, the most stable
      bromonium/Br3- ion pair would form spontaneously. The most stable of the three
      bromonium/Br3- ion pairs has a structure very similar to the observed X-ray
      structure. Free energies of activation and relative stabilities of reactants and
      products in CCl4 and CH2ClCH2Cl were also calculated with PCM using the united
      atom (UA0) cavity model and, in general, results similar to the gas phase were
      obtained. An optimized structure for the trans-1,2-dibromo product was also found
      at all levels of theory both in gas phase and in solution, but no transition
      state leading to the trans-1,2-dibromo product was obtained.

PMID- 18069808
TI  - Multilabeled classification approach to find a plant source for terpenoids.
AB  - Recently, we have built a classification model that is capable of assigning a
      given sesquiterpene lactone (STL) into exactly one tribe of the plant family
      Asteraceae from which the STL has been isolated. Although many plant species are
      able to biosynthesize a set of peculiar compounds, the occurrence of the same
      secondary metabolites in more than one tribe of Asteraceae is frequent. Building
      on our previous work, in this paper, we explore the possibility of assigning an
      STL to more than one tribe (class) simultaneously. When an object may belong to
      more than one class simultaneously, it is called multilabeled. In this work, we
      present a general overview of the techniques available to examine multilabeled
      data. The problem of evaluating the performance of a multilabeled classifier is
      discussed. Two particular multilabeled classification methods-cross-training with
      support vector machines (ct-SVM) and multilabeled k-nearest neighbors (ML-kNN)
      were applied to the classification of the STLs into seven tribes from the plant
      family Asteraceae. The results are compared to a single-label classification and
      are analyzed from a chemotaxonomic point of view. The multilabeled approach
      allowed us to (1) model the reality as closely as possible, (2) improve our
      understanding of the relationship between the secondary metabolite profiles of
      different Asteraceae tribes, and (3) significantly decrease the number of plant
      sources to be considered for finding a certain STL. The presented classification
      models are useful for the targeted collection of plants with the objective of
      finding plant sources of natural compounds that are biologically active or
      possess other specific properties of interest.

PMID- 18069809
TI  - Waiting cycle times and generalized Haldane equality in the steady-state cycle
      kinetics of single enzymes.
AB  - Enzyme kinetics are cyclic. A more realistic reversible three-step mechanism of
      the Michaelis-Menten kinetics is investigated in detail, and three kinds of
      waiting cycle times T, T+, T- are defined. It is shown that the mean waiting
      cycle times T, T+, and T- are the reciprocal of the steady-state cycle flux Jss,
      the forward steady-state cycle flux Jss+ and the backward steady-state cycle flux
      Jss, respectively. We also show that the distribution of T+ conditioned on T+<T-
      is identical to the distribution of T- conditioned on T-< T+, which is referred
      to as the generalized Haldane equality. Consequently, the mean waiting cycle time
      of T+ conditioned on T+<T- (T+|T+<T-) and the one of T- conditioned on T-<T+ (T
      |T-<T+) are both just the same as T. In addition, the forward and backward
      stepping probabilities p+ and p- are also defined and discussed, especially their
      relationship with the cycle fluxes and waiting cycle times. Furthermore, we
      extend the same results to the n-step cycle, and finally, experimental and
      theoretically based evidence are also included.

PMID- 18069810
TI  - Dielectric relaxation of aqueous solutions of hydrophilic versus amphiphilic
      peptides.
AB  - We report on molecular dynamics simulations of the frequency-dependent dielectric
      relaxation spectra at room temperature for aqueous solutions of a hydrophilic
      peptide and an amphiphilic peptide at two concentrations. We find that only the
      high-concentration amphiphilic peptide solution exhibits an anomalous dielectric
      increment over that of pure water, while the hydrophilic peptide exhibits a
      significant dielectric decrement. The dielectric component analysis carried out
      by decomposing these peptide solutions into peptide, hydration layer, and outer
      layer(s) of water clearly shows the presence of a unique dipolar component with a
      relaxation time scale on the order of approximately 25 ps (compared to the bulk
      water time scale of approximately 11 ps) that originates from the interaction
      between the hydration layer water and the outer layer(s) of water. Results
      obtained from the dielectric component analysis further show the emergence of a
      distinct and much lower frequency relaxation process for the high-concentration
      amphiphilic peptide compared to the hydrophilic peptide due to strong peptide
      dipolar couplings to all constituents, accompanied by a slowing of the structural
      relaxation in all water layers, giving rise to time scales close to approximately
      1 ns. We suggest that the molecular origin of the dielectric relaxation anomalies
      is due to frustration in the water network arising from the amphiphilic chemistry
      of the peptide that does not allow it to reorient on the picosecond time scale of
      bulk water motions. This explanation is consistent with the idea of the "slaving"
      of residue side chain motions to protein surface water, and furthermore offers
      the possibility that the anomalous dynamics observed from a number of
      spectroscopies arises at the interface of hydrophobic and hydrophilic domains on
      the protein surface.

PMID- 18069811
TI  - Controlled electrophoretic deposition of uniquely nanostructured star polymer
      films.
AB  - The controlled electrophoretic deposition of polystyrene/divinylbenzene (PS/DVB)
      star polymer films from a colloidal suspension is reported. Liquid suspensions,
      containing the PS/DVB star polymer, were prepared by injecting a dichloromethane
      (DCM) solution of the star polymer into a stratified liquid combination of hexane
      and DCM. A variety of hexane/DCM volume ratios were examined to identify the
      optimal solution conditions for electrophoretic deposition; thin films were
      produced from both unmixed and well-mixed hexane/DCM suspensions. Unmixed
      suspensions yielded spatially separated thin films, deposited in a controlled
      fashion, that were dependent on the polarity of the corresponding electrode.
      Films on the positive electrode differed in thickness, microstructure, and
      appearance from those formed on the negative electrode. In contrast, films
      produced from well-mixed hexane/DCM suspensions deposited uniformly across only
      the negative electrode. Atomic force microscopy studies revealed nanostructured
      surface morphologies that were unique to each of these films. Additionally, these
      microscopy studies shed light on the possible conformations of star polymers
      adsorbed on a surface. By controlling the composition and the mixing state of the
      solution and by controlling the bias of electrodes, we achieved controlled
      deposition of star polymer films with a specific nanostructure. These
      nanostructured films may have broad use in optical and biological device
      applications.

PMID- 18069812
TI  - Electronic transition dipole moment directions of reduced anionic flavin in
      stretched poly(vinyl alcohol) films.
AB  - The IR and UV/vis linear dichroic spectra of reduced anionic flavin
      mononucleotide (FMNH-) partially oriented in poly(vinyl alcohol) (PVA) films have
      been measured to determine the direction of the major electronic transition
      dipole moments. The IR linear dichroism (LD) was measured in the 1750-1350 cm(-1)
      region to provide the overall molecular orientation of the FMNH- in the stretched
      films. Time-dependent density functional theory using the B3LYP functional was
      used to calculate the normal modes and the transition dipole moments of reduced
      lumiflavin. The calculated normal modes assisted in IR band assignments and in
      the determination of the IR transition dipole moment directions which were
      required for the determination of the orientation parameters for FMNH- in PVA
      films. The UV/vis LD spectrum was measured over the 200-700 nm region and was
      resolved into contributions from three pi-->pi* transitions. The directions of
      the transitions are 90 degrees+/-4 degrees at 440 nm, 79 degrees+/-4 degrees at
      350 nm, and 93 degrees+/-4 degrees at 290 nm with counterclockwise rotations with
      respect to the N5-N10 axis. Comparison of the calculated and experimentally
      determined transition dipole moments allowed for refined assignment of the
      transition dipole moment directions. To our knowledge, this is the first
      experimental evidence that the 350-450 nm absorption arises from two unique
      transitions. Remarkably, the two lowest energy transition dipole moments for FMNH
      are nearly parallel to those obtained in prior studies for both oxidized and
      semiquinone flavin.

PMID- 18069813
TI  - Simulation of tunneling in enzyme catalysis by combining a biased propagation
      approach and the quantum classical path method: application to lipoxygenase.
AB  - The ability of using wave function propagation approaches to simulate isotope
      effects in enzymes is explored, focusing on the large H/D kinetic isotope effect
      of soybean lipoxygenase-1 (SLO-1). The H/D kinetic isotope effect (KIE) is
      calculated as the ratio of the rate constants for hydrogen and deuterium
      transfer. The rate constants are calculated from the time course of the H and D
      nuclear wave functions. The propagations are done using one-dimensional proton
      potentials generated as sections from the full multidimensional surface of the
      reacting system in the protein. The sections are obtained during a classical
      empirical valence bond (EVB) molecular dynamics simulation of SLO-1. Since the
      propagations require an extremely long time for treating realistic activation
      barriers, it is essential to use an effective biasing approach. Thus, we develop
      here an approach that uses the classical quantum path (QCP) method to evaluate
      the quantum free energy change associated with the biasing potential. This
      approach provides an interesting alternative to full QCP simulations and to other
      current approaches for simulating isotope effects in proteins. In particular,
      this approach can be used to evaluate the quantum mechanical transmission factor
      or other dynamical effects, while still obtaining reliable quantized activation
      free energies due to the QCP correction.

PMID- 18069814
TI  - Tautomeric equilibrium, stability, and hydrogen bonding in 2'-deoxyguanosine
      monophosphate complexed with Mg2+.
AB  - The tautomeric equilibrium and hydrogen bonding in nucleotide 2'-deoxyguanosine
      monophosphate that interacts with hydrated Mg2+ cation (4H2O.Mg[dGMP]) were
      studied at the MP2/cc-pVDZ//B3LYP/cc-pVDZ and B3LYP/aug-cc-pVTZ//B3LYP/cc-pVDZ
      levels of theory. The Mg2+ ion forms two inner-shell contacts with the
      nucleotide, similar to small phosphorylated molecules under physiological
      conditions. The presence of the phosphate group and the hydrated magnesium cation
      leads to a change in guanine tautomeric equilibrium of 4H2O.Mg[dGMP] in
      comparison to free guanine. The influence of the phosphate group and the
      magnesium cation on tautomeric equilibrium is larger in the anti conformation
      where the P=O-->Mg and Mg<--N7 coordinate bonds are formed. The canonical oxo
      form of guanine is more stable (by 6-8 kcal/mol) than the O6-hydroxo form in anti
      conformation. Thus, the interaction with Mg2+ ion is capable of further
      suppressing the likelihood of a spontaneous transient formation of the rare
      tautomer. In the syn conformation of 4H2O.Mg[dGMP], the interaction of the
      guanine nucleobase with the phosphate group and the magnesium cation is not as
      strong as in the anti conformation, and the relative stability of guanine
      tautomers is close to those in free guanine.

PMID- 18069815
TI  - Measurement of the adsorption at solid-liquid interfaces from the pressure
      dependence of contact angles.
AB  - Earlier studies have indicated that in an isothermal three-phase system, the
      liquid-phase pressure at the three-phase line, xL3, may be viewed as the
      independent variable of the contact angle, theta, and that adsorption at the
      solid-liquid interface is the mechanism relating them. When the liquid-vapor
      interface is axi-symmetric, we show that theta can be predicted as a function of
      xL3 and that by measuring theta(xL3), the amount adsorbed at the solid-liquid
      interface can be determined. We consider water in differently sized borosilicate
      glass cylinders. For progressively larger cylinders, xL3 increases with cylinder
      radius, but when a particularly sized cylinder is rotated about it longitudinal
      axis, xL3 is decreased. The observed value of theta in each case is found to be
      in close agreement with that predicted. A Gibbs model of the interphase is used,
      and the Gibbs adsorption at the solid-liquid interface is found to be negative.
      As xL3 increases above its value at wetting, the amount adsorbed at the solid
      liquid interface becomes progressively more negative. Negative adsorption is
      shown to mean that the concentration of the fluid component is greater in the
      bulk liquid than in the interphase and that the difference in concentration
      increases as xL3 is increased. The data is used to investigate the hypothesis
      that the curvature of the three-phase line affects theta through line tension,
      but we find no relation between line tension and theta. There is an apparent
      relation between the curvature of the liquid-vapor interface, CLV and theta, but
      this is shown to be because CLV affects xL3.

PMID- 18069816
TI  - Molecular dynamics simulation of the structure, dynamics, and thermostability of
      the RNA hairpins uCACGg and cUUCGg.
AB  - Classical replica-exchange molecular dynamics simulations are performed to study
      structure, dynamics and thermostability of the 14-mer RNA hairpins uCACGg and
      cUUCGg. Despite of the different sequence and closing base pair of the two
      systems, recent NMR studies have shown that the tetraloop CACG is strikingly
      similar in overall geometry and hydrogen bonding to the canonical UUCG tetraloop.
      On the other hand, the two systems differ significantly in their functionality
      and thermostability. The simulations confirm the structural similarities of the
      two RNA hairpins at room temperature but also reveal that the UUCG loop is more
      flexible than the CACG loop. Concerning the functionality, the CACG loop shows a
      stronger attitude to donate hydrogens than the UUCG loop, although their global
      solvent accessible surface is quite similar. The simulations qualitatively
      reproduce the experimentally found difference in melting temperatures (20 K). In
      the case of the uCACGg hairpin, the thermal unfolding occurs cooperatively in an
      all-or-none fashion, while the cUUCGg hairpin shows less cooperativity but
      exhibits intermediate states during the unfolding process.

PMID- 18069817
TI  - Physical properties of ionic liquids consisting of the 1-butyl-3
      methylimidazolium cation with various anions and the
      bis(trifluoromethylsulfonyl)imide anion with various cations.
AB  - Physical properties of 4 room-temperature ionic liquids consisting of the 1-butyl
      3-methylimidazolium cation with various perfluorinated anions and the
      bis(trifluoromethylsulfonyl)imide (Tf2N-) anion with 12 pyrrolidinium-, ammonium
      , and hydroxyl-containing cations are reported. Electronic structure methods are
      used to calculate properties related to the size, shape, and dipole moment of
      individual ions. Experimental measurements of phase-transition temperatures,
      densities, refractive indices, surface tensions, solvatochromic polarities based
      on absorption of Nile Red, 19F chemical shifts of the Tf2N- anion, temperature
      dependent viscosities, conductivities, and cation diffusion coefficients are
      reported. Correlations among the measured quantities as well as the use of
      surface tension and molar volume for estimating Hildebrand solubility parameters
      of ionic liquids are also discussed.

PMID- 18069818
TI  - Photodecarbonylation of alpha-diketones: a mechanistic study of reactions leading
      to acenes.
AB  - Poly(acene)s are significant compounds for various electronic applications. A
      clean, one-step synthesis involves alpha-diketones (2-4), which undergo facile
      Strating-Zwanenburg photodecarbonylation producing the corresponding poly(acene)s
      (i.e., anthracene, hexacene, and heptacene, respectively). Compounds 2-4 show
      weak fluorescence (lambdaF=approximately 525-530 nm and PhiF=approximately 0.1
      0.4%) and phosphorescence (lambdaPh=approximately 565-570 nm) and have a small
      singlet-triplet energy gap (S1-T1 gap, approximately 4 kcal/mol) that facilitates
      rapid intersystem crossing from the singlet to the triplet state. Both the
      singlet states (tauS=approximately 20-218 ps) and the triplet states
      (tauT=approximately 370 ps to <7 ns) of 2-4 are short-lived, while the
      decarbonylation of 2-4 is a rapid process occurring within 7 ns from both the
      singlet and the triplet manifolds. The nanosecond laser flash photolysis of 4
      also reveals the T-T absorption of heptacene (580 nm, tau=approximately 11
      micros).

PMID- 18069819
TI  - Diffusion of dextran probes in a self-assembled fibrous gel composed of two
      dimensional arborols.
AB  - Two-dimensional arborols are bolaform amphiphiles in which a central, hydrophobic
      spacer separates twin hydrophilic ends. Under appropriate conditions, these
      relatively small molecules assemble into very long fibers; subsequently, the
      system gels if the arborol concentration is sufficiently high. The diffusion of
      linear or slightly branched dextran probes in 3 and 6% arborol gels, as
      determined by fluorescence photobleaching recovery, resembles that of dextrans in
      water, suggesting a highly open network structure. Melting the gels produces
      almost no change in diffusion of the dextran probes. Small-angle X-ray scattering
      (SAXS) of wet arborol gels at different concentrations and temperatures reveals
      the diameter of the repeating unit of the fibers to be 8.26+/-0.68 nm. This
      dimension, which is independent of concentration and temperature, exceeds the
      length of a single arborol molecule by about a factor of 3. Rheological
      investigation identifies the linear response regime of the gels and permits an
      examination of the weak correlation between dextran probe diffusion and gel
      viscoelasticity.

PMID- 18069820
TI  - Lateral diffusion of proteins in the plasma membrane: spatial tessellation and
      percolation theory.
AB  - The obstructed diffusion of proteins in the plasma membrane is studied using
      computer simulation and an analysis using spatial tessellation and percolation
      theory. The membrane is modeled as a two-dimensional space with fixed hard disc
      obstacles, and the proteins are modeled as hard discs. The simulations show a
      transition from normal to anomalous diffusion as the area fraction, phim, of
      obstacles is increased and to confined diffusion for area fractions above the
      pecolation threshold, which occurs for phim=0.22. A Voronoi tessellation
      procedure is used to map the continuous space system onto an effective lattice
      model, with the connectivity of bonds determined from a geometric criterion. The
      estimate of the percolation threshold obtained from this lattice model is in
      excellent agreement with the simulation results, although the nature of the
      dynamics in the continuous space model is different from lattice models. At high
      obstacle area fractions (but below the percolation threshold), the primary mode
      of transport is a hopping motion between voids, consistent with experiment. The
      simulations and analysis emphasize the importance of structural correlations
      between obstacles.

PMID- 18069821
TI  - Structure of (NH4)3GaF6 investigated by multinuclear magic-angle spinning NMR
      spectroscopy in comparison with rietveld refinement.
AB  - The structure of ammonium gallium cryolite (NH(4))(3)GaF(6) was investigated by
      (19)F and (69,71)Ga magic-angle spinning (MAS) NMR in comparison with X-ray
      powder diffraction followed by Rietveld refinement. In agreement with previous
      thermodynamic measurements, NMR experiments on (NH(4))(3)GaF(6) support the model
      of rigid GaF(6) octahedra. At high spinning speeds (30 kHz), the scalar coupling
      between the six equivalent (19)F nuclei and (69,71)Ga can be directly observed in
      the powder spectra. The coupling constants are J(19)F(69)Ga = 197 Hz and
      J(19)F(71)Ga = 264 Hz. To explain the (71)Ga spectra recorded at 3 kHz a small
      distribution of quadrupolar frequencies has to be included. The spread of the
      spinning sidebands hints to a largest nu(Q) value of 28 kHz for (71)Ga. This can
      be explained by the occurrence of highly symmetric GaF(6) octahedra, which are
      tilted against the surrounding atoms. In addition, the incomplete motional
      excitation does not average out the quadrupolar effects. NMR findings are in
      discrepancy to those of Rietveld refinement. As result it appears that X-ray
      diffraction is not sensitive enough to deliver proper results.

PMID- 18069822
TI  - Bluish-white emission from radical carbonyl impurities in amorphous Al(2)O(3)
      prepared via the Pechini-type sol-gel process.
AB  - Many efforts have been devoted to exploring novel luminescent materials that do
      not contain expensive or toxic elements, or do not need mercury vapor plasma as
      the excitation source. In this paper, amorphous Al2O3 powder samples were
      prepared via the Pechini-type sol-gel process. The resulting samples were
      characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR)
      spectroscopy, field emission scanning electron microscopy (FESEM),
      photoluminescence (PL) excitation and emission spectra, kinetic decay, and
      electron paramagnetic resonance (EPR). The obtained amorphous Al2O3 powder
      samples annealed at 500 and 600 degrees C exhibit bright bluish-white emission
      centered at 430 and 407 nm, respectively. The luminescent mechanisms of the
      amorphous Al2O3 powder samples can be ascribed to the carbon-related impurities
      such as radical carbonyl species. The calculated band structure of the defective
      amorphous Al2O3 agrees well with the results of spectral analysis and the
      proposed luminescent mechanism.

PMID- 18069823
TI  - Exchange interactions and electron delocalization in the mixed-valence cluster
      V(4)(IV)V(2)(V)O(7)(OC(2)H(5))(12).
AB  - The mixed-valence cluster compound V4IVV2VO7(OC2H5)12 was studied by X-band
      electron paramagnetic resonance (EPR) in the temperature range of 4.2-293 K.
      According to X-ray diffraction study, the crystal structure of the compound was
      described by a R3m space group at 295 K (four d1 electrons are equally
      delocalized on all vanadium ions) and changed to a P21/n space group on cooling
      the crystals to 173 K (the electrons are preferably localized on the four
      equatorial vanadium ions). The EPR spectra originate from the S = 1 total spin
      states with the fine structure averaged to a single Lorentzian line and from the
      S = 2 total spin states with fine structure partly averaged in the temperature
      range of 295-200 K and well averaged below 45-50 K. The states of S = 1 and S = 2
      of comparable energy (DeltaE approximately 2 cm(-1); ES=1 < ES=2) were shown to
      be the lowest ones. The VIV <--> VV unpaired electron transfers together with
      isotropic Heisenberg exchange were shown to determine the total spin states
      composition and the intracluster dynamics of the compound. Two types of electron
      transfers were assumed: the single-jump transfer leading to the averaged
      configurations of the V4IVV2V <--> V3IVVV VIVVV type and to the splitting of the
      total spin states by intervals comparable in magnitude with the isotropic
      exchange parameter J approximately 100 cm-1 and the double-jump transfer
      resulting in dynamics. Temperature dependence of the transition rates nutr was
      observed. In the range of 295-210 K, the value of nutr = (0.5-0.6) x 10(10) s(-1)
      is sufficient for averaging the fine structure of the S = 1 states, and below 45
      K the value of nutr approximately 1.5 x 10(10) s(-1) also averages the fine
      structure of the S = 2 state. A change in the localization plane of the VIV ions
      in the temperature range of 40-50 K was discovered.

PMID- 18069824
TI  - Analysis of the spin lattice model for the spin-gapped layered compounds
      Na(3)Cu(2)SbO(6) and Na(2)Cu(2)TeO(6) on the basis of electronic structure
      calculations.
AB  - The spin lattice model for the spin-gapped layered magnetic solids Na3Cu2SbO6 and
      Na2Cu2TeO6 was examined by evaluating the three spin exchange interactions of
      their Cu2MO6 (M = Sb, Te) layers in terms of spin dimer analysis based on
      extended Huckel tight binding calculations and mapping analysis based on first
      principles density functional theory electronic band structure calculations. For
      both compounds, our calculations show that the two strongest spin exchange
      interactions, that is, the Cu-O...O-Cu super-superexchange (J2) and the Cu-O-Cu
      superexchange (J1) interactions, form alternating chains that interact weakly
      through the Cu-O-Cu superexchange (J3) interactions. The dominant one of the
      three spin exchange interactions is J2, and it is antiferromagnetic in agreement
      with the fact that both of the compounds are spin gapped. For Na3Cu2SbO6 and
      Na2Cu2TeO6, the superexchange J1 is calculated to be ferromagnetic, hence,
      leading to the alternating chain model in which antiferromagnetic and
      ferromagnetic spin exchange interactions alternate. This picture does not agree
      with the recent experimental analysis, which showed that the temperature
      dependent magnetic susceptibilities of both compounds should be described by the
      alternating chain model in which two antiferromagnetic spin exchange interactions
      of different strengths alternate.

PMID- 18069825
TI  - Heterometallic cuboidal clusters M(3)M'Q(4) (M = Mo, W; M'= Sn, Pb, As, Sb; Q =
      S, Se): from coordination compounds to supramolecular adducts.
AB  - Reactions of the incomplete cuboidal clusters [M3Q4(acac)3(py)3]+ (M = Mo, W; Q =
      S, Se) with group 14 and 15 metal complexes with the s2p0 electronic
      configuration (AsPh3, SbPh3, SbCl3, SbI3, PbI3-, SnCl3-) led to heterometal
      incorporation with the formation of cuboidal clusters of the type
      [M3(EX3)Q4(acac)3(py)3]n+ (n = 0 for Sn, Pb; n = 1 for As, Sb), whose structures
      were determined by X-ray diffraction. The cuboidal clusters can be described as
      complexes of the cluster tridentate ligand [M3Q4(acac)3(py)3]+ (mu2-chalcogen
      atoms as donors) with the EX3, where the E atom attains a distorted octahedral
      coordination. Analysis based on the bond distances E-Q gives the following
      sequence of affinity: As < Sb; Pb < Sn approximately Sb; SbPh3 < SbI3
      approximately SbCl3; W3S4 < W3Se4. Interaction energies at the gas phase between
      [W3Q4(acac)3(py)3]+ (Q = S, Se) and SbX3 (X = I, Ph) were computed at the DFT
      level (BP86/TZP). The magnitude of the interaction depends strongly on the
      substituents at Sb, and the replacement of iodine by the phenyl group decreases
      the interaction energy from -9.21 to -2.70 kcal/mol and from -12.73 to -3.85
      kcal/mol for the W3SbS4 and W3SbSe4 cores, respectively.

PMID- 18069826
TI  - Self-assembled copper(II) coordination polymers derived from aminopolyalcohols
      and benzenepolycarboxylates: structural and magnetic properties.
AB  - The new copper(II) or copper(II)/sodium(I) 1D coordination polymers
      [Cu2(Hmdea)2(mu-H2O)(mu2-tpa)]n.2nH2O (1), [Cu2(H2tipa)2(mu2-ipa)]n.4nH2O (2),
      [Cu2(H2tea)2Na(H2O)2(mu2-tma)]n.6nH2O (3), [Cu2(H2tea)2(mu2-ipa)]n.nH2O (4a), and
      [Cu2(H2tea)2{mu3-Na(H2O)3}(mu3-ipa)]n(NO3)n.0.5nH2O (4b) have been prepared in
      aqueous medium by self-assembly from copper(II) nitrate, aminopolyalcohols
      [methyldiethanolamine (H2mdea), triisopropanolamine (H3tipa), and triethanolamine
      (H3tea)] as main chelating ligands and benzenepolycarboxylic acids [terephthalic
      (H2tpa), isophthalic (H2ipa), and trimesic (H3tma) acid] as spacers. They have
      been characterized by IR spectroscopy, elemental and single-crystal X-ray
      diffraction analyses, the latter indicating the formation of unusual multinuclear
      metal cores interconnected by various benzenepolycarboxylate spacers, leading to
      distinct wavelike, zigzag, or linear 1D polymeric metal-organic chains. These are
      further extended to 2D or 3D hydrogen-bonded supramolecular networks via
      extensive interactions with the intercalated crystallization water molecules. The
      latter are associated, also with aqua ligands, by hydrogen bonds resulting in
      acyclic (H2O)3 clusters in 1, (H2O)8 clusters in 2, infinite 1D water chains in
      3, and disordered water-nitrate associates in 4b, all playing a key role in the
      structure stabilization and its extension to further dimensions. Variable
      temperature magnetic susceptibility measurements have shown that 1-4 exhibit a
      moderately strong ferromagnetic coupling through the alkoxo bridge. The small Cu
      O-Cu bridging angle and the large out-of-plane displacement of the carbon atom of
      the alkoxo group accounts for this behavior. The magnetic data have been analyzed
      by means of a dinuclear and a 1D chain model, and the magnetic parameters have
      been determined. The magnetic exchange coupling in 3, to our knowledge, is the
      highest found in alkoxo-bridged copper(II) complexes.

PMID- 18069827
TI  - Structural alternatives for the formation of halogenophosphine-phosphenium
      complexes.
AB  - NMR studies of reactions between some N-heterocyclic and acyclic diamino
      phosphenium ions (R2N)2P+ and P-chlorophosphines (R2N)2PCl suggest that the
      reactants interact via chloride scrambling rather than by formation of P-P bonded
      phosphenium-phosphine complexes. Computational studies of reactions between model
      ions (R'2N)2P+ and neutral phosphines (R'2N)2PX (X = F, Cl, Br) confirm that in
      the gas phase the formation of halide-bridged adducts is indeed preferred and
      only for the most electrophilic cation an alternative but energetically less
      favorable P-P bonded structure was found. The halide-bridged adducts feature
      nearly C2-symmetrical P...X...P arrays (for X = Cl, Br) or are loose molecular
      complexes arising from electrostatic interaction between nearly unperturbed
      fragments (for X = F). In the latter case, a P...F...P-bridged structure was
      located as a transition state of a fluoride transfer reaction. The formation of
      the adducts appears to be controlled by electrostatic rather than orbital
      interactions. Consideration of solvent effects by a polarizable continuum model
      indicates a destabilization of the adducts versus the isolated fragments and
      suggests that in solution extensive dissociation occurs. The computations further
      reveal a large solvent-induced lengthening of the P-Cl bonds in N-heterocyclic
      halogenophosphines which implies that the unusual P-Cl distances observed for
      these species are, to a large part, attributable to intermolecular influences.

PMID- 18069829
TI  - Helicates, boxes, and polymers from simple pyridine-alcohol ligands: the impact
      of the identity of the transition metal ion.
AB  - The coordination chemistry of 6-methylpyridine-2-methanol (1) and enantiopure (R)
      1-(6-methylpyridin-2-yl)ethanol (2) with a range of divalent first-row transition
      metal salts has been investigated in an effort to determine whether hydrogen
      bonded helicates will form, as observed for cobalt(II) salts. Hydrogen-bonded
      helicates, [Cu2(1)2(1-H)2X2] (X = Cl, Br), were only observed upon combining 1
      with CuCl2 and CuBr2 in MeOH solution. Other metal salts led to alternative
      products, viz. Cu(ClO4)2 in the presence of base gives [Cu2(1)2(1-H)2](ClO4)2,
      ZnCl2 and ZnBr2 give the 1-D helical coordination polymers [Zn(1-H)Cl]infinity
      and [Zn(1-H)Br]infinity, a mixture of NiCl2 and Ni(OAc)2 produces the [Ni4(1
      H)4Cl2(OAc)2(MeOH)2] cubane, NiCl2 leads to the [Ni4(1-H)4Cl4(MeOH)4] cubane,
      while MnCl2 gives the known cubane [Mn4(1-H)6Cl4]. The reaction of 2 with CuCl2
      produces the mononuclear complex Lambda-[Cu(2)2Cl]Cl, while reaction with CuBr2
      leads to a dimer, Lambda,Lambda-[Cu2(2)3(2-H)Br2]Br, which is held together by a
      single hydrogen bond between the monomeric subunits. The solid-state CD spectra
      of these latter complexes were recorded and found to be very similar. The
      temperature-dependent magnetic behavior of [Cu2(1)2(1-H)2X2] (X = Cl, Br),
      [Cu2(1)2(1-H)2](ClO4)2, [Cu2(2)3(2-H)Br2]Br, and [Ni4(1-H)4Cl2(OAc)2(MeOH)2] was
      investigated. Weak antiferromagnetic coupling between the copper(II) centers is
      mediated by the hydrogen bonds in the [Cu2(1)2(1-H)2X2] (X = Cl, Br) complexes.

PMID- 18069828
TI  - Hydrothermal synthesis, structures, and photoluminescent properties of
      benzenepentacarboxylate bridged networks incorporating zinc(II)-hydroxide
      clusters or zinc(II)-carboxylate layers.
AB  - The first coordination compounds of partially or wholly deprotonated
      benzenepentacarboxylic acid (H5L) were synthesized in the presence or absence of
      auxiliary 2,2'-bipyridyl (2,2'-bpy) and 1,10-phenanthroline (phen) ligands, and
      their crystal structures and photoluminescent properties were characterized.
      Their formulas are [Zn6(mu3-OH)2(L)2(H2O)6]n (1), [Zn5(mu3-OH)2(HL)2(2,2'-bpy)2]n
      (2), [Zn2(HL)(phen)2(H2O)2]n (3), and [Zn5(L)2(phen)4(H2O)3]n.2nH2O (4). Both 1
      and 2 are three-dimensional (3D) zinc(II)-hydroxide cluster based coordination
      frameworks. 1 contains distorted chairlike hexanuclear Zn6(mu3-OH)2 cluster units
      as secondary building blocks. Each Zn6(mu3-OH)2 unit connects six others through
      the three-connected nodes of L5- ligands into a 3D rigid and condensed
      coordination network, whereas in 2, each pentanuclear Zn5(mu3-OH)2 unit connects
      the other six ones through the three-connected [HL]4- nodes into a 3D network in
      the simple cubic packing mode. 3 has two-dimensional (2D) Zn(II)-carboxylate
      supramolecular layers constructed from a one-dimensional (1D) coordination chain
      structure by hydrogen bonds of the water and mu5-[HL]4- bridges, whereas 4 has 2D
      coordination layers composed of Zn(II) and mu8-L5- bridges. The adjacent
      coordination assemblies in 3 and 4 are further extended by hydrogen bonds and
      pi...pi interactions into 3D supramolecular architectures. 1-4 are
      photoluminescent active materials, and their photofluorescent properties are
      closely related to their intrinsic structure arrangements.

PMID- 18069830
TI  - Diastereomerically enriched analogues of the water-soluble phosphine PTA.
      Synthesis of phenyl(1,3,5-triaza-7-phosphatricyclo[3.3.1.1(3,7)]dec-6-yl)methanol
      (PZA) and the sulfide PZA(S) and X-ray crystal structures of the oxide PZA(O) and
      [Cp*IrCl(2)(PZA)].
AB  - A diastereomerically enriched analogue of 1,3,5-triaza-7-phosphaadamantane (PTA)
      was obtained by the reaction of PTA lithium salt with benzaldehyde to give the
      water-soluble derivative phenyl(1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]dec-6
      yl)methanol (PZA, 1) as a mixture of two diastereoisomers. PZA derivatives
      phenyl(1,3,5-triaza-7-phospha-tricyclo[3.3.1.13,7]dec-6-yl)methanol sulfide
      [PZA(S), 2] and oxide [PZA(O), 3] were also synthesized. The latter was isolated
      in the solid state, and the X-ray crystal structure of a single diastereoisomer
      was obtained. Compound 1 was used as a k1-P monodentate ligand toward
      iridium(III) moieties, and the piano-stool complex [Cp*IrCl2(PZA)] (4) was
      obtained as a mixture of diastereoisomers both in solution and in the solid
      state.

PMID- 18069831
TI  - Charge-transfer-to-solvent-driven dissolution dynamics of I- (H2O)2-5 upon
      excitation: excited-state ab initio molecular dynamics simulations.
AB  - In contrast to the extensive theoretical investigation of the solvation
      phenomena, the dissolution phenomena have hardly been investigated theoretically.
      Upon the excitation of hydrated halides, which are important substances in
      atmospheric chemistry, an excess electron transfers from the anionic precursor
      (halide anion) to the solvent and is stabilized by the water cluster. This
      results in the dissociation of hydrated halides into halide radicals and electron
      water clusters. Here we demonstrate the charge-transfer-to-solvent (CTTS)-driven
      femtosecond-scale dissolution dynamics for I-(H2O)n=2-5 clusters using excited
      state (ES) ab initio molecular dynamics (AIMD) simulations employing the complete
      active-space self-consistent-field (CASSCF) method. This study shows that after
      the iodine radical is released from I-(H2O)n=2-5, a simple population decay is
      observed for small clusters (2 </= n </= 4), while rearrangement to stabilize the
      excess electron to an entropy-driven structure is seen for n = 5. These results
      are in excellent agreement with the previous ultrafast pump-probe experiments.
      For the first approximately 30 fs of the simulations, the iodine plays an
      important role in rearranging the hydrogen orientations (although the water
      network hardly changes), which increases the kinetic energy of the cluster.
      However, approximately 50 fs after the excitation, the role of the iodine radical
      is no longer significant. After approximately 100 fs, the iodine radical is
      released, and the solvent molecules rearrange themselves to a lower free energy
      structure. The CTTS-driven dissolution dynamics could be useful in designing the
      receptors which are able to bind and release ions in host-guest chemistry.

PMID- 18069832
TI  - 2-(4,5,6,7-Tetrafluorobenzimidazol-2-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1- H
      imidazole-3-oxide-1-oxyl, a hydrogen-bonded organic quasi-1D ferromagnet.
AB  - The title radical (F4BImNN) is a stable nitronylnitroxide that forms hydrogen
      bonded NH... ON chains in the solid state. The chains assemble the F4BImNN
      molecules to form stacked contacts between the radical groups, in a geometry that
      is expected to exhibit ferromagnetic (FM) exchange based on spin polarization
      (SP) models. The experimental magnetic susceptibility of F4BImNN confirms the
      expectation, showing 1-D Heisenberg chain FM exchange behavior over 1.8-300 K
      with an intrachain exchange constant of Jchain/k = +22 K. At lower temperatures,
      ac magnetic susceptibility and variable field heat capacity measurements show
      that F4BImNN acts as a quasi-1-D ferromagnet. The dominant ferromagnetic exchange
      interaction is attributable to overlap between spin orbitals of molecules within
      the hydrogen-bonded chains, consistent with the SP model expectations. The chains
      appear to be antiferromagnetically exchange coupled, giving cusps in the ac
      susceptibility and zero field heat capacity at lower temperatures. The results
      indicate that the sample orders magnetically at about 0.7 K. The magnetic heat
      capacity ordering cusp shifts to lower temperatures as external magnetic field
      increases, consistent with forming a bulk antiferromagnetic phase below a Neel
      temperature of TN(0) = 0.72 K, with a critical field of Hc approximately 1800 Oe.
      The interchain exchange is estimated to be zJ/k congruent with (-)0.1 K.

PMID- 18069836
TI  - The sugar conformation governs (6-4) photoproduct formation at the dinucleotide
      level.
AB  - The LNA dinucleotide mimic of TpT whose two-sugar puckers are locked in the C3'
      endo conformation selectively produces the corresponding cyclobutane pyrimidine
      dimer under 254 nm irradiation. In the natural series (TpT) the sugar puckers are
      in a major C2'-endo sugar conformation and the (6-4) photoproduct is also
      produced. Consequently, this study demonstrates that the C2'-endo conformation of
      the sugar pucker is necessary for (6-4) photoproduct formation.

PMID- 18069837
TI  - Small Au and Pt clusters at the anatase TiO2(101) surface: behavior at terraces,
      steps, and surface oxygen vacancies.
AB  - The adsorption properties of Au and Pt metal nanoclusters on TiO2 anatase (101)
      were calculated using density functional theory. Structures and energetics of
      adsorbed Au and Pt monomers, dimers, and trimers at clean anatase TiO2(101)
      terraces and two major step edges, as well as O-vacancies, were systematically
      determined. The theoretical predictions were tested by vapor-depositing small
      coverages of Au and Pt on anatase (101) and investigating the resulting clusters
      with Scanning Tunneling Microscopy. On the clean surface, Au shows a strong
      tendency to form large clusters that nucleate on step edges. A preference for
      adsorption at type D-(112) steps is observed, which is probably a result of
      kinetic effects. For Pt, clusters as small as monomers are observed on the
      terraces, in agreement with the predicted large binding energy of 2.2 eV. Step
      edges play a less important role than in the case of Au. Oxygen vacancies,
      produced by electron irradiation, dramatically influence the growth of Au, while
      the nucleation behavior of Pt was found to be less affected.

PMID- 18069838
TI  - Rapid assembly of complex 3D siloxane architectures.
AB  - Few routes to well-defined 3D silicone structures exist because of their
      susceptibility to depolymerization/metathesis in the presence of acids or bases.
      The Lewis acid B(C6F5)3 can be employed to condense hydrosilanes with
      alkoxysilanes, producing siloxanes and alkanes (R3SiH+R'OSiR' '3 --> R3SiOSiR' '3
      + R'H). We demonstrate that balancing the steric demands at both the hydrosilane
      and alkoxysilanes, and the careful control of reaction conditions, permits clean
      condensation reactions to occur in the absence of competing metathesis processes.
      The resulting linear or highly branched siloxane compounds can be rapidly and
      easily assembled into explicit, complex 3D silicone structures in high yield.

PMID- 18069839
TI  - A luminescent sensor for tyrosine phosphorylation.
AB  - We have developed a luminogenic probe for tyrosine phosphorylation based on a
      short peptide sequence containing an iminodiacetate moiety near the site of
      phosphorylation. In response to kinase activity, the probe provides a strong
      luminescence enhancement, resulting from the increased ability of the probe to
      bind and sensitize Tb3+ and Eu3+ ions upon phosphorylation.

PMID- 18069840
TI  - Highly efficient energy transfer in the light harvesting system composed of three
      kinds of boron-dipyrromethene derivatives.
AB  - A light-harvesting system containing three kinds of BODIPY fluorophores was
      synthesized. It exhibited very strong absorption in the region from 300 to 700
      nm, and the energy transfer within it was highly efficient.

PMID- 18069841
TI  - Preparation of fully substituted anilines for the synthesis of functionalized
      indoles.
AB  - A wide range of highly functionalized indoles were prepared by the successive
      magnesiation of readily available o-alkynyl protected anilines using TMPMgCl.LiCl
      or LDA, followed by a KH-mediated cyclization reaction.

PMID- 18069842
TI  - Michael addition-elimination reactions of chiral enolates with ethyl 3
      halopropenoates.
AB  - Key dienoic or dienal substructures of cytotoxic macrolides amphidinolide E and
      dictyostatin have been prepared via a Michael addition (followed by elimination
      of X-) of chiral enolates on beta-halo derivatives of ethyl acrylate, with full
      retention of the initial E or Z configuration. Evans oxazolidin-2-ones and our
      related thiazolidin-2-ones, as well as a fine-tuning of the reaction conditions,
      have been essential. Many chiral building blocks are accessible from these
      adducts.

PMID- 18069843
TI  - First total synthesis of trimeric indole alkaloid, psychotrimine.
AB  - The first total synthesis of (+/-)-psychotrimine, a novel trimeric indole
      alkaloid isolated from Psychotria rostrata, was achieved. In the total synthesis,
      the copper-mediated intramolecular and intermolecular aminations of halobenzenes,
      which respectively contributed to the construction of a pyrrolidinoindoline core
      and the installation of a third tryptamine unit, were used as key steps.

PMID- 18069844
TI  - Mechanistic insights into the stereocontrolled synthesis of hexahydropyrrolo[2,3
      b]indoles by electrophilic activation of tryptophan derivatives.
AB  - A three-step mechanism involving the formation and rearrangement of an
      intermediate with indoline-azetidine spirocyclic core structure was shown by DFT
      computations to account for the electrophilic cyclization of tryptophan
      derivatives to hexahydropyrrolo[2,3-b]indoles. The corresponding 3a-bromo
      derivatives have been obtained in high yields and synthetically useful exo/endo
      ratios.

PMID- 18069845
TI  - Asymmetric lithiation-substitution of amines involving rearrangement of borates.
AB  - Asymmetric lithiation of substituted benzylamines, N-Boc-pyrrolidine, or N-Boc
      indoline using Beak's methodology was followed by electrophilic quench with
      trialkylboranes. The resulting borate intermediates rearrange with concomitant C
      N bond breakage to give, after oxidation, chiral secondary alcohols with high
      enantioselectivity.

PMID- 18069846
TI  - Oligomannan synthesis using ionic liquid supported glycosylation.
AB  - The synthesis of complex oligosaccharides has been a challenge for researchers.
      Herein, we describe a strategy for the synthesis of an activated oligomannan 1
      that employs ionic liquid (IL) support glycosylation methodology on an IL-tagged
      mannosyl fluoride donor. This method is capable of rapidly producing linear
      alpha(1-->6) oligomannan thioglycosides in a convenient and cost-effective manner
      without the need of column purification after each glycosylation step.

PMID- 18069847
TI  - Monitoring of the adenovirus production process by flow cytometry.
AB  - Adenovirus (Ad) has become the vector of choice for gene therapy clinical
      protocols worldwide; it is the only viral vector to date that has been licensed
      for use in a gene therapy treatment. There is, however, a need to develop a
      simple, reliable at-line method to monitor the production of virus and
      recombinant proteins (r-proteins) that have no intrinsic reporter properties.
      Here we utilize flow cytometry to measure cell size, granularity, and DNA content
      in a single-step analysis and to correlate these parameters to the production of
      a type-5 Ad (Ad5) expressing the recombinant green fluorescent protein (GFP).
      Clear correlations between these parameters and productivity are made, with
      forward scatter and DNA content showing the highest correlation coefficients, 0.9
      and 0.83 for virus production and r-protein production, respectively. Measuring
      these parameters requires little or no processing of the cells from culture to
      analysis. These parameters have been used successfully to monitor, at-line, the
      amount of Ad and r-protein product in a 293-Ad system.

PMID- 18069848
TI  - Molecular transformations of unsaturated thiacrown ethers.
AB  - Unsaturated thiacrown ethers with 15, 18, and 21 members were oxidized to
      sulfoxides by the reaction with m-CPBA. The reaction with t-BuOCl at -20 degrees
      C also afforded sulfoxides, whereas the reaction at room temperature yielded cis
      trans isomerized compounds. The cis-trans isomerized compound was also obtained
      by the photochemical reaction or by the reaction with NCS and NCP. Meanwhile, the
      reaction with NBS and NBP provided an acetal via 1,2-bridged bromonium
      intermediate.

PMID- 18069849
TI  - Fullerene-like chemistry at the interior carbon atoms of an alkene-centered
      C26H12 geodesic polyarene.
AB  - The title compound (1) undergoes 1,2-addition reactions of both electrophilic and
      nucleophilic reagents preferentially at the "interior" carbon atoms of the
      central 6:6-bond to give fullerene-type adducts 2, 3, 4, and 5. Such fullerene
      like chemistry is unprecedented for a topologically 2-dimensional polycyclic
      aromatic hydrocarbon and qualifies this geodesic polyarene as a "bridge" between
      the old flat world of polycyclic aromatic hydrocarbons (PAHs) and the new round
      world of fullerenes. The relief of pyramidalization strain, as in the addition
      reactions of fullerenes, presumably contributes to the atypical mode of
      reactivity seen in 1. Molecular orbital calculations, however, reveal features of
      the nonalternant pi system in 1 that may also play an important role. Thus, the
      fullerene-like chemistry of 1 may be driven by two or more factors, the relative
      importances of which are difficult to discern.

PMID- 18069850
TI  - Structural studies on cycloadducts of furan, 2-methoxyfuran, and 5
      trimethylsilylcyclopentadiene with maleic anhydride and N-methylmaleimide.
AB  - The early stages of the retro-Diels-Alder reaction are clearly apparent in the
      structures of the cycloadducts formed between furan or 5
      trimethylsilylcyclopentadiene with maleic anhydride and N-methylmaleimide. The
      degree of lengthening of the C-C bonds that break in this reaction is clearly
      related to the known reactivity of these cycloadducts toward this reaction. In
      the structures of the cycloadducts 21 and 22 derived from 2-methoxyfuran, the
      early stages of an alternative fragmentation reaction are apparent, consistent
      with the reactivity of these compounds in solution.

PMID- 18069851
TI  - First triazole-bridged unsymmetrical porphyrin dyad via click chemistry.
AB  - Click chemistry has been successfully applied in the synthesis of the first
      example of a triazole-bridged porphyrin dyad containing N(2)S(2) porphyrin and
      N(4) or ZnN(4) porphyrin subunits, and fluorescence study indicated a possibility
      of singlet-singlet energy transfer from the N(4) or ZnN(4) porphyrin subunit to
      the N(20S(2) porphyrin subunit.

PMID- 18069852
TI  - Diastereoselective Mukaiyama aldol reaction of 2-(trimethylsilyloxy)furan
      catalyzed by bismuth triflate.
AB  - We have developed an efficient vinylogous Mukaiyama aldol reaction of 2
      (trimethylsilyloxy)furan with various aromatic aldehydes mediated by bismuth
      triflate in low catalyst loading (1 mol %). The reaction proceeds rapidly and
      affords the corresponding 5-(hydroxy(aryl)methyl)furan-2(5H)-ones in high yields
      with good to very good diastereoselectivities (dr up to >98:2). Such
      selectivities, albeit previously reported with other Lewis acids, could this time
      be achieved with a much lower catalyst loading. 5-(Hydroxy(alkyl)methyl)furan
      2(5H)-ones derived from ketones could also be obtained with good
      diastereoselectivities.

PMID- 18069853
TI  - 2,6,7-trithiabicyclo[2.2.2]octanes as promising photolabile tags for
      combinatorial encoding.
AB  - The adducts of trithiabicyclo[2.2.2]octane (TTBO) and carbonyl compounds undergo
      efficient photoinduced fragmentation with quantum yields comparable to that of
      dithiane adducts. The effect of the third sulfur on the stability of the
      respective radical cations and radicals is examined computationally and
      experimentally in a laser flash photolysis study. A straightforward synthetic
      approach to a variety of 4-substituted trithiabicyclo[2.2.2]octanes from 3-bromo
      2,2-bis(bromomethyl)propanol is developed, making a diverse set of mass
      differentiated photolabile tags readily available for combinatorial encoding.

PMID- 18069854
TI  - Synthesis and structural revision of (+/-)-laurentristich-4-ol.
AB  - The structure of tetracyclic natural sesquiterpene laurentristich-4-ol was
      revised based on its synthetic studies. The proposed and the revised structures
      of laurentristich-4-ol were both synthesized with SmI(2)-mediated ketyl radical
      cyclization as the key step to construct the spirocyclic ether skeleton.

PMID- 18069855
TI  - Nucleophilic addition to iminium ethers in the preparation of functionalized N
      alkyl heterocycles.
AB  - Bicyclic iminium ethers can be synthesized by the reactions of ketones with
      hydroxyalkyl azides. These cationic species react with a variety of nucleophiles
      via two possible pathways. The initially formed, kinetic product arises from
      direct addition to the iminium carbon in the substrate. In some cases, the
      initial adduct reverts to the starting iminium ether and the ultimate product
      arises from nucleophilic displacement at the O-alkyl group to afford the
      terminally functionalized N-substituted amide. The behavior of a range of
      nucleophiles was studied by using several iminium ethers. In general, the
      relevant pathway could be identified by characterization of the product formed.
      For hydroxide addition, which can afford only one product regardless of
      mechanism, the reaction was shown to arise by the kinetic pathway, using (18)O
      labeled hydroxide. A one-pot synthesis of functionalized lactams entailing
      treatment of ketones first with hydroxyalkyl azides followed by nucleophilic
      addition was also developed.

PMID- 18069856
TI  - Infrared absorbing croconaine dyes: synthesis and metal ion binding properties.
AB  - Quinaldine-based croconaine dyes synthesized by the condensation reaction between
      croconic acid and the respective quinaldinium salts are described. These dyes
      exhibit absorption maximum in the infrared region (840-870 nm) with high molar
      extinction coefficients (1-5 x 10(5) M(-1) cm(-1)) and have very low fluorescence
      quantum yields. Upon binding to divalent metal ions, these dyes were found to
      form complexes with a 2:1 stoichiometry having high association constants of the
      order of 10(11)-10(14) M(-2), while the monovalent metal ions showed negligible
      affinity. The binding of the croconaine dye 3d with divalent metal ions
      especially Zn(2+), Pb(2+), and Cd(2+) led to significant chelation-enhanced
      fluorescence emission. The broadening of the aromatic signals, vinylic and N
      methyl protons and the negligible changes at the aliphatic region of the dye 3d
      in the (1)H NMR spectrum in the presence of Zn(2+), indicate that the binding
      occurs at the carbonyl groups of the croconyl ring. The shift in the croconyl
      carbonyl stretching frequency in the [3d-Zn(2+)] complex analyzed through FT-IR
      analysis further confirms the involvement of two electron-rich carbonyl groups of
      the croconyl moiety in the complexation. These results demonstrate that the
      binding of the divalent metal ions at the carbonyl oxygens of these infrared
      absorbing dyes can be favorably utilized for the development of potential sensors
      for the detection of metal ions and further can be exploited as sensitizers for
      photodynamic therapeutic applications.

PMID- 18069857
TI  - Recent Reviews.
AB  - Reviews are listed in order of appearance in the sources indicated. In
      multidisciplinary review journals, only those reviews which fall within the scope
      of this Journal are included. Sources are listed alphabetically in three
      categories: regularly issued review journals and series volumes, contributed
      volumes, and other monographs. Titles are numbered serially, and these numbers
      are used for reference in the index. Major English-language sources of critical
      reviews are covered. Encyclopedic treatises, annual surveys such as Specialist
      Periodical Reports, and compilations of symposia proceedings are omitted. This
      installment of Recent Reviews covers principally the middle part of the 2007
      literature. Previous installment: J. Org. Chem. 2007, 72(20), 7809-16.

PMID- 18069859
TI  - Characterization of monolayer formation on aluminum-doped zinc oxide thin films.
AB  - The optical and electronic properties of aluminum-doped zinc oxide (AZO) thin
      films on a glass substrate are investigated experimentally and theoretically.
      Optical studies with coupling in the Kretschmann configuration reveal an angle
      dependent plasma frequency in the mid-IR for p-polarized radiation, suggestive of
      the detection of a Drude plasma frequency. These studies are complemented by
      oxygen depletion density functional theory studies for the calculation of the
      charge carrier concentration and plasma frequency for bulk AZO. In addition, we
      report on the optical and physical properties of thin film adlayers of n
      hexadecanethiol (HDT) and n-octadecanethiol (ODT) self-assembled monolayers
      (SAMs) on AZO surfaces using reflectance FTIR spectroscopy, X-ray photoelectron
      spectroscopy (XPS), contact angle, and near-edge X-ray absorption fine structure
      (NEXAFS) spectroscopy. Our characterization of the SAM deposition onto the AZO
      thin film reveals a range of possible applications for this conducting metal
      oxide.

PMID- 18069860
TI  - Modeling the drying of ink-jet-printed structures and experimental verification.
AB  - This article presents a numerical model that was developed for the drying of ink
      jet-printed polymer solutions after filling the pixels in a polymer LED display.
      The model extends earlier work presented in the literature while still
      maintaining a practical approach in limiting the number of input parameters
      needed. Despite some rigorous assumptions, the model is in fair agreement with
      experimental data from a pre-pilot ink-jet printing line. Comparison inside a
      single pixel is shown, as well as a general trend in which the amount of polymer
      that is transported out of the central part of the pixel decreases with the rate
      of viscosity increase as a function of polymer concentration. Moreover, the
      effect of a varying solute diffusion coefficient is studied.

PMID- 18069858
TI  - Impact of mutations on the midpoint potential of the [4Fe-4S]+1,+2 cluster and on
      catalytic activity in electron transfer flavoprotein-ubiquinone oxidoreductase
      (ETF-QO).
AB  - Electron-transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is an iron
      sulfur flavoprotein that accepts electrons from electron-transfer flavoprotein
      (ETF) and reduces ubiquinone from the Q-pool. ETF-QO contains a single [4Fe
      4S]2+,1+ cluster and one equivalent of FAD, which are diamagnetic in the isolated
      oxidized enzyme and can be reduced to paramagnetic forms by enzymatic donors or
      dithionite. Mutations were introduced by site-directed mutagenesis of amino acids
      in the vicinity of the iron-sulfur cluster of Rhodobacter sphaeroides ETF-QO.
      Y501 and T525 are equivalent to Y533 and T558 in the porcine ETF-QO. In the
      porcine protein, these residues are within hydrogen-bonding distance of the
      Sgamma of the cysteine ligands to the iron-sulfur cluster. Y501F, T525A, and
      Y501F/T525A substitutions were made to determine the effects on midpoint
      potential, activity, and EPR spectral properties of the cluster. The integrity of
      the mutated proteins was confirmed by optical spectra, EPR g-values, and spin
      lattice relaxation rates, and the cluster to flavin point-dipole distance was
      determined by relaxation enhancement. Potentiometric titrations were monitored by
      changes in the CW EPR signals of the cluster and semiquinone. Single mutations
      decreased the midpoint potentials of the iron-sulfur cluster from +37 mV for wild
      type to -60 mV for Y501F and T525A and to -128 mV for Y501F/T525A. Lowering the
      midpoint potential resulted in a decrease in steady-state ubiquinone reductase
      activity and in ETF semiquinone disproportionation. The decrease in activity
      demonstrates that reduction of the iron-sulfur cluster is required for activity.
      There was no detectable effect of the mutations on the flavin midpoint
      potentials.

PMID- 18069861
TI  - Drop mixing in a microchannel for lab-on-a-chip platforms.
AB  - We present theory, simulations, and experiments for discrete drop mixing in
      microchannels. The drops are placed sequentially in a channel and then moved at a
      set velocity to achieve mixing. The mixing occurs in three different regimes
      (diffusion-dominated, dispersion-dominated, and convection-dominated) depending
      on the Peclet number (Pe) and the drop dimensions. Introducing the modified
      Peclet number (Pe*), we show asymptotic curves that can be used to predict the
      mixing time and the required distance for mixing for any of the three regimes.
      Simulations of the mixing experiments using COMSOL agree with the theoretical
      limits. In our experimental work, we used a polydimethylsiloxane (PDMS)
      microchannel with a membrane air bypass valve to remove the air between drops.
      This approach enables precise control of the mixing and merging site.
      Experimental, simulation, and theoretical results all agree and show that mixing
      can occur in fractions of a second to hours, depending on the parameters used.

PMID- 18069862
TI  - Global study of myoglobin-surfactant interactions.
AB  - Surfactants interact with proteins in multifarious ways which depend on
      surfactant concentration and structure. To obtain a global overview of this
      process, we have analyzed the interaction of horse myoglobin (Mb) with an anionic
      (SDS) and cationic (CTAC) surfactant, using both equilibrium titration techniques
      and stopped-flow kinetics. Binding and kinetics of conformational changes can be
      divided into a number of different regions (five below the cmc and one above)
      with very distinct features (broadly similar between the two surfactants, despite
      their difference in head group and chain length), which nuance the classical view
      of biphasic binding prior to micellization. In stage A, fairly weak interactions
      lead to a linear decrease in thermal stability. This gives way to a more
      cooperative process in stage B, where aggregates (presumably hemimicelles) start
      to form on the protein surface, leading to global denaturation (loss of a thermal
      transition) and biphasic unfolding kinetics. This is consolidated in stage C with
      titratable surfactant adsorption. Adsorption of this surfactant species leads to
      significant changes in kinetics, namely, inhibition of unfolding kinetics in CTAC
      and altered unfolding amplitudes in SDS, though the process is still biphasic in
      both surfactants. Stage D commences the reduction in exothermic binding signals,
      leading to further uptake of 5 (SDS) or 31 (CTAC) surfactant molecules without
      any major changes in protein conformation. In stage E many more surfactant
      molecules (46 SDS and 39 CTAC) are bound, presumably as quasi-micellar
      structures, and we observe a very slow unfolding phase in SDS, which disappears
      as we reach the cmc. Above the cmc, the unfolding rates remain essentially
      constant in SDS, but increase significantly in CTAC, possibly because binding of
      bulk micelles removes the inhibition by hemimicellar aggregates. Our work
      highlights the fascinating richness of conformational changes that proteins can
      undergo in the presence of molecules with self-assembling properties.

PMID- 18069863
TI  - Morphological control of synthesis and anomalous magnetic properties of 3-D
      branched Pt nanoparticles.
AB  - Morphology-controllable platinum nanostructures could be obtained by modulating
      the growth kinetics in oleylamine. The nanostructures evolve from spherical
      particles to branched networks with decreasing reaction temperature, and the
      complexity of the branched-network nanostructures increases with the extended
      reaction period. Size-dependent magnetic properties and enhanced ferromagnetism
      in dodecanethiol-capped Pt branched nanostructures indicate that the permanent
      magnetic moments are probably introduced by broken symmetry and charge transfer
      because charge transfers more effectively from dodecanethiol than from
      oleylamine.

PMID- 18069866
TI  - Unique carbon-nanotube field-effect transistors with asymmetric source and drain
      contacts.
AB  - We have fabricated a type of unique single-walled carbon nanotube field-effect
      transistor, in which the channel length is only 90 nm and aluminum and gold are
      used as its drain and source electrodes, respectively. The channel conductance
      oscillations caused by single-electron tunneling through the asymmetric barriers
      at the drain and source contacts are observed up to 100 K. Above 100 K, the
      tunneling fades away, and thermionic emission dominates the conductance at
      sufficiently negative gate voltages. At room temperature, the device shows diode
      like characteristics with a maximum current rectification ratio of approximately
      10(4).

PMID- 18069865
TI  - Detection of DNA sequences using an alternating electric field in a nanopore
      capacitor.
AB  - Molecular dynamics simulations revealed that back-and-forth motion of DNA strands
      through a 1 nm diameter pore exhibits sequence-specific hysteresis that arises
      from the reorientation of the DNA bases in the nanopore constriction. Such
      hysteresis of the DNA motion results in detectable changes of the electrostatic
      potential at the electrodes of the nanopore capacitor and in a sequence-specific
      drift of the DNA strand under an oscillating transmembrane bias. A strategy is
      suggested for sequencing DNA in a nanopore using the electric field that
      alternates periodically in time.

PMID- 18069867
TI  - Probing the structure of DNA-carbon nanotube hybrids with molecular dynamics.
AB  - DNA-carbon nanotube hybrids (DNA-CN) are novel nanoscale materials that consist
      of single-wall carbon nanotubes (SWCN) coated with a self-assembled monolayer of
      single-stranded DNA (ssDNA). Recent experiments on DNA-CN have shown that this
      material offers a remarkable set of technologically useful properties such as
      facilitation of SWCN sorting, chemical sensing, and detection of DNA
      hybridization. Despite the importance of DNA-CN, a detailed understanding of its
      microscopic structure and physical properties is lacking. To address this, we
      have performed classical all-atom molecular dynamics (MD) simulations exploring
      the self-assembly mechanisms, structure, and energetic properties of this
      nanomaterial. MD reveals that SWCN induces ssDNA to undergo a spontaneous
      conformational change that enables the hybrid to self-assemble via the pi-pi
      stacking interaction between ssDNA bases and SWCN sidewall. ssDNA is observed to
      spontaneously wrap about SWCN into compact right- or left-handed helices within a
      few nanoseconds. Helical wrapping is driven by electrostatic and torsional
      interactions within the sugar-phosphate backbone that result in ssDNA wrapping
      from the 3' end to the 5' end.

PMID- 18069868
TI  - Intersubband decay of 1-D exciton resonances in carbon nanotubes.
AB  - We have studied intersubband decay of E22 excitons in semiconducting carbon
      nanotubes experimentally and theoretically. Photoluminescence excitation line
      widths of semiconducting nanotubes with chiral indicess (n,m) can be mapped onto
      a connectivity grid with curves of constant (n - m) and (2n + m). Moreover, the
      global behavior of E22 line widths is best characterized by a strong increase
      with energy irrespective of their (n-m)mod(3) = +/-1 family affiliation. Solution
      of the Bethe-Salpeter equations shows that the E22 line widths are dominated by
      phonon assisted coupling to higher momentum states of the E11 and E12 exciton
      bands. The calculations also suggest that the branching ratio for decay into
      exciton bands vs free carrier bands, respectively is about 10:1.

PMID- 18069869
TI  - Single-molecule charge transfer and bonding at an organic/inorganic interface:
      tetracyanoethylene on noble metals.
AB  - We have studied the structural and electronic properties of tetracyanoethylene
      (TCNE) molecules on different noble-metal surfaces using scanning tunneling
      spectroscopy and density functional theory. Striking differences are observed in
      the TCNE behavior on Au, Ag, and Cu substrates in the submonolayer limit. We
      explain our findings by a combination of charge-transfer and lattice-matching
      properties for TCNE across substrates that results in a strong variation of
      molecule-molecule and molecule-substrate interactions. These results have
      significant implications for future organic/inorganic nanoscopic devices
      incorporating molecule-based magnetism.

PMID- 18069870
TI  - Microwave impedance spectroscopy of dense carbon nanotube bundles.
AB  - We have performed impedance spectroscopy of dense carbon nanotube (CNT) bundles
      in the broad frequency range from 10 MHz to 67 GHz. Dense CNT bundles were formed
      on sharp tips from aqueous suspension by ac dielectrophoresis and incorporated
      into on-wafer test structures. The frequency response of the bundles can be fit
      to a model with frequency-independent elements in the entire frequency range up
      to 67 GHz strongly suggesting that CNT properties do not depend on the frequency
      throughout the whole frequency range. The measurements at microwave frequencies
      allowed separate characterization of the bundle/metal electrode contacts and the
      bundle bulk. Effects of different CNT fabrication and suspension processing
      routes on bundle characteristics were identified. We have also made a preliminary
      estimation of the average inductance per current carrying shell in the bundles.
      For good quality nanotube bundles, the inductance has been found to fall within
      the range from approximately 3.5 to 40 nH/microm. With decreasing nanotube
      quality, the implemented estimation procedure yields higher values with a large
      uncertainty. Systematic measurements of devices with individual nanotubes are
      required to provide more accurate data.

PMID- 18069871
TI  - Boron-based organometallic nanostructures: hydrogen storage properties and
      structure stability.
AB  - Transition-metal (TM) boride and carboride nanostructures are studied as model
      organometallic materials for hydrogen storage. The dispersed TM atoms function as
      H2 sorption centers on the surface of the boron or carbon-boron substrate. The
      flexibility offered in the variety of possible structures permits the study of
      the effect of the TM-TM distance on the storage capacity. When the TMs are too
      close to one another, TM-TM bonding reduces the capacity. Even when separated by
      distances larger than the normal TM-TM bond length, delocalization of TM valence
      electrons can still lower the hydrogen capacity. An optimal TM-TM distance for
      the structural motifs studied here is approximately 6 A. Our study also permitted
      the evaluation of new TM boride nanostructures. We predict a low-energy single
      walled scandium triboride (ScB3) nanotube that can bind approximately 6.1 wt %
      hydrogen with a binding energy of 22 approximately 26 kJ/mol.

PMID- 18069872
TI  - Controlled release of chol-TEG-DNA from Nano- and micropatterned SU-8 surfaces by
      a spreading lipid film.
AB  - We report the controlled release of immobilized cholesteryl-tetraethyleneglycol
      DNA (chol-DNA) from micropatterned SU-8 surfaces by a spreading lipid film. The
      release of chol-DNA is rapid and on the order of the spreading rate of the lipid
      film beta = 1-3 microm2/s ( approximately 10(5) molecules of DNA per second). The
      lipid film serves as a poor solvent for the DNA adduct, which upon contact
      redistributes into the aqueous phase. Thus, the release of DNA is accompanied by
      a change in surface hydrophobicity. The method can be used for creating arbitrary
      concentration profiles of DNA in solution over time or to dynamically change
      surface properties on demand in, for example, micro- and nanofluidic devices.
      Examples of DNA release from spiral, comb, meander, and triangular as well as
      from nanoscale SU-8 lanes are shown.

PMID- 18069873
TI  - Synthesis and isolation of molybdenum atomic wires.
AB  - One of the main challenges in nanoscience and nanotechnology consists in the
      production and isolation of metallic atomic-scale nanowires (Benzryadin, C. N.;
      Lau, A.; Tinkham, M. Q. Nature 2000, 404, 971-974; Zach, M. P.; Ng, K. H.;
      Penner, R. M. Science 2000, 290, 2120-2123; Nilius, N.; Wallis, T. M.; Ho, W.
      Science 2002, 297, 1853-1856.). Here we report a unique and controllable way of
      isolating individual atomic molybdenum (Mo) chains by their encapsulation inside
      double-walled carbon nanotubes, exhibiting inner diameters ranging from 0.6 to
      0.8 nm. We have found that these individual atomic chains form spontaneously
      within the hollow core of tubes in the absence of any reducing agent. We believe
      that these atomic-scale nanowires could now be studied without suffering
      oxidation, so that their physical and chemical properties are elucidated.

PMID- 18069874
TI  - Transparent active matrix organic light-emitting diode displays driven by
      nanowire transistor circuitry.
AB  - Optically transparent, mechanically flexible displays are attractive for next
      generation visual technologies and portable electronics. In principle, organic
      light-emitting diodes (OLEDs) satisfy key requirements for this application
      transparency, lightweight, flexibility, and low-temperature fabrication. However,
      to realize transparent, flexible active-matrix OLED (AMOLED) displays requires
      suitable thin-film transistor (TFT) drive electronics. Nanowire transistors
      (NWTs) are ideal candidates for this role due to their outstanding electrical
      characteristics, potential for compact size, fast switching, low-temperature
      fabrication, and transparency. Here we report the first demonstration of AMOLED
      displays driven exclusively by NW electronics and show that such displays can be
      optically transparent. The displays use pixel dimensions suitable for hand-held
      applications, exhibit 300 cd/m2 brightness, and are fabricated at temperatures
      suitable for integration on plastic substrates.

PMID- 18069875
TI  - Normal and shear forces generated during the ordering (directed assembly) of
      confined straight and curved nanowires.
AB  - The effects of shape on nanowire interactions and shear-induced ordering were
      studied. Both the normal and lateral forces were sensitive to the particles'
      curvature. (i) No adhesion was observed between the confining surfaces, and the
      force profiles were short-ranged and mostly reversible for straight wires but
      longer-ranged and irreversible for curved wires. (ii) Structural phase
      transitions can occur in confined nanoparticle films. (iii) During shearing,
      straight wires order or align more easily than curved wires.

PMID- 18069876
TI  - PX DNA triangle oligomerized using a novel three-domain motif.
AB  - Structural DNA nanotechnology is directed at building objects, lattices, and
      arrays from cohesive interactions between DNA molecules. The predominant means of
      doing this takes advantage of the information inherent in Watson-Crick base
      pairing in duplex formation and in sticky-ended cohesion. Nevertheless, other
      forms of nucleic acid cohesion are also known, particularly paranemic edge
      sharing interactions (PX). Here we report the formation of a triangular species
      that has four strands per edge, held together by PX interactions. We demonstrate
      by nondenaturing gel electrophoresis and by atomic force microscopy (AFM) that we
      can combine a partial triangle with other strands to form a four-stranded
      molecule that is robust. By combining them with a new mixed-fusion type of three
      domain molecule, we demonstrate by AFM that these triangles can be self-assembled
      into a linear array.

PMID- 18069877
TI  - Transparent, conductive graphene electrodes for dye-sensitized solar cells.
AB  - Transparent, conductive, and ultrathin graphene films, as an alternative to the
      ubiquitously employed metal oxides window electrodes for solid-state dye
      sensitized solar cells, are demonstrated. These graphene films are fabricated
      from exfoliated graphite oxide, followed by thermal reduction. The obtained films
      exhibit a high conductivity of 550 S/cm and a transparency of more than 70% over
      1000-3000 nm. Furthermore, they show high chemical and thermal stabilities as
      well as an ultrasmooth surface with tunable wettability.

PMID- 18069879
TI  - What this geriatrician does for exercise.

PMID- 18069880
TI  - Sleep disorders in the elderly.
AB  - Sleep disorders are common but frequently underdiagnosed in the elderly.
      Aggressive screening and appropriate therapy can significantly improve general
      health and well-being. Treating sleep disorders in the elderly requires
      appreciation of the physiologic changes of aging. Insomnia is common and
      frequently secondary to modifiable factors. Nonpharmacologic and behavioral
      approaches are underused. Pharmacotherapy should be used cautiously and
      conservatively.

PMID- 18069881
TI  - Prosthetic joint infection: when to suspect it, how to manage it.
AB  - The number of prosthetic joint infections in the United States is rising because
      of our aging population and the increasing number of adults undergoing joint
      replacement surgery. The cardinal symptom of prosthetic joint infection is
      recurrent pain in the joint. Fever and leukocytosis may be absent in elderly
      patients, particularly in late infections. Diagnosis requires joint aspiration or
      operative biopsy. Successful outcomes require expert orthopedic surgical
      management and prolonged antibiotic therapy. Treatment should be individualized
      according to the specific pathogen and clinical circumstances.

PMID- 18069882
TI  - Recognition and management of aortic stenosis in the elderly.
AB  - Angina pectoris, syncope or near-syncope, and congestive heart failure (CHF) are
      the 3 cardinal manifestations of aortic stenosis (AS) in the elderly. Prolonged
      duration and late peaking of the aortic systolic ejection murmur best
      differentiate severe from mild AS. The agreement in quantitation of AS severity
      between Doppler echocardiography and cardiac catheterization is approximately
      95%. The average survival is 3 years after the onset of angina pectoris or
      syncope and 1.5 to 2 years after the onset of CHF in patients with severe AS who
      does not undergo surgery. Indications for aortic valve replacement (AVR), for use
      of warfarin after AVR in patients with mechanical prostheses, and for use of
      aspirin or warfarin after AVR in patients with bioprostheses are listed in the
      article.

PMID- 18069883
TI  - Bumps on the legs.

PMID- 18069884
TI  - The modular organization of domain structures: insights into protein-protein
      binding.
AB  - Domains are the building blocks of proteins and play a crucial role in protein
      protein interactions. Here, we propose a new approach for the analysis and
      prediction of domain-domain interfaces. Our method, which relies on the
      representation of domains as residue-interacting networks, finds an optimal
      decomposition of domain structures into modules. The resulting modules comprise
      highly cooperative residues, which exhibit few connections with other modules. We
      found that non-overlapping binding sites in a domain, involved in different
      domain-domain interactions, are generally contained in different modules. This
      observation indicates that our modular decomposition is able to separate protein
      domains into regions with specialized functions. Our results show that modules
      with high modularity values identify binding site regions, demonstrating the
      predictive character of modularity. Furthermore, the combination of modularity
      with other characteristics, such as sequence conservation or surface patches, was
      found to improve our predictions. In an attempt to give a physical interpretation
      to the modular architecture of domains, we analyzed in detail six examples of
      protein domains with available experimental binding data. The modular
      configuration of the TEM1-beta-lactamase binding site illustrates the energetic
      independence of hotspots located in different modules and the cooperativity of
      those sited within the same modules. The energetic and structural cooperativity
      between intramodular residues is also clearly shown in the example of the
      chymotrypsin inhibitor, where non-binding site residues have a synergistic effect
      on binding. Interestingly, the binding site of the T cell receptor beta chain
      variable domain 2.1 is contained in one module, which includes structurally
      distant hot regions displaying positive cooperativity. These findings support the
      idea that modules possess certain functional and energetic independence. A
      modular organization of binding sites confers robustness and flexibility to the
      performance of the functional activity, and facilitates the evolution of protein
      interactions.

PMID- 18069885
TI  - Neuraminidase inhibitor resistance in influenza: assessing the danger of its
      generation and spread.
AB  - Neuraminidase Inhibitors (NI) are currently the most effective drugs against
      influenza. Recent cases of NI resistance are a cause for concern. To assess the
      danger of NI resistance, a number of studies have reported the fraction of
      treated patients from which resistant strains could be isolated. Unfortunately,
      those results strongly depend on the details of the experimental protocol.
      Additionally, knowing the fraction of patients harboring resistance is not too
      useful by itself. Instead, we want to know how likely it is that an infected
      patient can generate a resistant infection in a secondary host, and how likely it
      is that the resistant strain subsequently spreads. While estimates for these
      parameters can often be obtained from epidemiological data, such data is lacking
      for NI resistance in influenza. Here, we use an approach that does not rely on
      epidemiological data. Instead, we combine data from influenza infections of human
      volunteers with a mathematical framework that allows estimation of the parameters
      that govern the initial generation and subsequent spread of resistance. We show
      how these parameters are influenced by changes in drug efficacy, timing of
      treatment, fitness of the resistant strain, and details of virus and immune
      system dynamics. Our study provides estimates for parameters that can be directly
      used in mathematical and computational models to study how NI usage might lead to
      the emergence and spread of resistance in the population. We find that the
      initial generation of resistant cases is most likely lower than the fraction of
      resistant cases reported. However, we also show that the results depend strongly
      on the details of the within-host dynamics of influenza infections, and most
      importantly, the role the immune system plays. Better knowledge of the
      quantitative dynamics of the immune response during influenza infections will be
      crucial to further improve the results.

PMID- 18069886
TI  - Stereochemical criteria for prediction of the effects of proline mutations on
      protein stability.
AB  - When incorporated into a polypeptide chain, proline (Pro) differs from all other
      naturally occurring amino acid residues in two important respects. The phi
      dihedral angle of Pro is constrained to values close to -65 degrees and Pro lacks
      an amide hydrogen. Consequently, mutations which result in introduction of Pro
      can significantly affect protein stability. In the present work, we describe a
      procedure to accurately predict the effect of Pro introduction on protein
      thermodynamic stability. Seventy-seven of the 97 non-Pro amino acid residues in
      the model protein, CcdB, were individually mutated to Pro, and the in vivo
      activity of each mutant was characterized. A decision tree to classify the
      mutation as perturbing or nonperturbing was created by correlating stereochemical
      properties of mutants to activity data. The stereochemical properties including
      main chain dihedral angle phi and main chain amide H-bonds (hydrogen bonds) were
      determined from 3D models of the mutant proteins built using MODELLER. We
      assessed the performance of the decision tree on a large dataset of 163 single
      site Pro mutations of T4 lysozyme, 74 nsSNPs, and 52 other Pro substitutions from
      the literature. The overall accuracy of this algorithm was found to be 81% in the
      case of CcdB, 77% in the case of lysozyme, 76% in the case of nsSNPs, and 71% in
      the case of other Pro substitution data. The accuracy of Pro scanning mutagenesis
      for secondary structure assignment was also assessed and found to be at best 69%.
      Our prediction procedure will be useful in annotating uncharacterized nsSNPs of
      disease-associated proteins and for protein engineering and design.

PMID- 18069887
TI  - Getting started in probabilistic graphical models.

PMID- 18069888
TI  - A novel inhibitory mechanism of mitochondrion-dependent apoptosis by a
      herpesviral protein.
AB  - Upon viral infection, cells undergo apoptosis as a defense against viral
      replication. Viruses, in turn, have evolved elaborate mechanisms to subvert
      apoptotic processes. Here, we report that a novel viral mitochondrial anti
      apoptotic protein (vMAP) of murine gamma-herpesvirus 68 (gammaHV-68) interacts
      with Bcl-2 and voltage-dependent anion channel 1 (VDAC1) in a genetically
      separable manner. The N-terminal region of vMAP interacted with Bcl-2, and this
      interaction markedly increased not only Bcl-2 recruitment to mitochondria but
      also its avidity for BH3-only pro-apoptotic proteins, thereby suppressing Bax
      mitochondrial translocation and activation. In addition, the central and C
      terminal hydrophobic regions of vMAP interacted with VDAC1. Consequently, these
      interactions resulted in the effective inhibition of cytochrome c release,
      leading to the comprehensive inhibition of mitochondrion-mediated apoptosis.
      Finally, vMAP gene was required for efficient gammaHV-68 lytic replication in
      normal cells, but not in mitochondrial apoptosis-deficient cells. These results
      demonstrate that gammaHV-68 vMAP independently targets two important regulators
      of mitochondrial apoptosis-mediated intracellular innate immunity, allowing
      efficient viral lytic replication.

PMID- 18069889
TI  - Self-regulation of Candida albicans population size during GI colonization.
AB  - Interactions between colonizing commensal microorganisms and their hosts play
      important roles in health and disease. The opportunistic fungal pathogen Candida
      albicans is a common component of human intestinal flora. To gain insight into C.
      albicans colonization, genes expressed by fungi grown within a host were studied.
      The EFH1 gene, encoding a putative transcription factor, was highly expressed
      during growth of C. albicans in the intestinal tract. Counterintuitively, an efh1
      null mutant exhibited increased colonization of the murine intestinal tract, a
      model of commensal colonization, whereas an EFH1 overexpressing strain exhibited
      reduced colonization of the intestinal tract and of the oral cavity of athymic
      mice, the latter situation modeling human mucosal candidiasis. When inoculated
      into the bloodstream of mice, both efh1 null and EFH1 overexpressing strains
      caused lethal infections. In contrast, other mutants are attenuated in virulence
      following intravenous inoculation but exhibited normal levels of intestinal
      colonization. Finally, although expression of several genes is dependent on
      transcription factor Efg1p during laboratory growth, Efg1p-independent expression
      of these genes was observed during growth within the murine intestinal tract.
      These results show that expression of EFH1 regulated the level of colonizing
      fungi, favoring commensalism as opposed to candidiasis. Also, different genes are
      required in different host niches and the pathway(s) that regulates gene
      expression during host colonization can differ from well-characterized pathways
      used during laboratory growth.

PMID- 18069890
TI  - Mechanism of inducible nitric oxide synthase exclusion from mycobacterial
      phagosomes.
AB  - Mycobacterium tuberculosis is sensitive to nitric oxide generated by inducible
      nitric oxide synthase (iNOS). Consequently, to ensure its survival in
      macrophages, M. tuberculosis inhibits iNOS recruitment to its phagosome by an
      unknown mechanism. Here we report the mechanism underlying this process, whereby
      mycobacteria affect the scaffolding protein EBP50, which normally binds to iNOS
      and links it to the actin cytoskeleton. Phagosomes harboring live mycobacteria
      showed reduced capacity to retain EBP50, consistent with lower iNOS recruitment.
      EBP50 was found on purified phagosomes, and its expression increased upon
      macrophage activation, paralleling expression changes seen with iNOS.
      Overexpression of EBP50 increased while EBP50 knockdown decreased iNOS
      recruitment to phagosomes. Knockdown of EBP50 enhanced mycobacterial survival in
      activated macrophages. We tested another actin organizer, coronin-1, implicated
      in mycobacterium-macrophage interaction for contribution to iNOS exclusion. A
      knockdown of coronin-1 resulted in increased iNOS recruitment to model latex bead
      phagosomes but did not increase iNOS recruitment to phagosomes with live
      mycobacteria and did not affect mycobacterial survival. Our findings are
      consistent with a model for the block in iNOS association with mycobacterial
      phagosomes as a mechanism dependent primarily on reduced EBP50 recruitment.

PMID- 18069891
TI  - Edema toxin impairs anthracidal phospholipase A2 expression by alveolar
      macrophages.
AB  - Bacillus anthracis, the etiological agent of anthrax, is a spore-forming gram
      positive bacterium. Infection with this pathogen results in multisystem
      dysfunction and death. The pathogenicity of B. anthracis is due to the production
      of virulence factors, including edema toxin (ET). Recently, we established the
      protective role of type-IIA secreted phospholipase A2 (sPLA2-IIA) against B.
      anthracis. A component of innate immunity produced by alveolar macrophages (AMs),
      sPLA2-IIA is found in human and animal bronchoalveolar lavages at sufficient
      levels to kill B. anthracis. However, pulmonary anthrax is almost always fatal,
      suggesting the potential impairment of sPLA2-IIA synthesis and/or action by B.
      anthracis factors. We investigated the effect of purified ET and ET-deficient B.
      anthracis strains on sPLA2-IIA expression in primary guinea pig AMs. We report
      that ET inhibits sPLA2-IIA expression in AMs at the transcriptional level via a
      cAMP/protein kinase A-dependent process. Moreover, we show that live B. anthracis
      strains expressing functional ET inhibit sPLA2-IIA expression, whereas ET
      deficient strains induced this expression. This stimulatory effect, mediated
      partly by the cell wall peptidoglycan, can be counterbalanced by ET. We conclude
      that B. anthracis down-regulates sPLA2-IIA expression in AMs through a process
      involving ET. Our study, therefore, describes a new molecular mechanism
      implemented by B. anthracis to escape innate host defense. These pioneering data
      will provide new molecular targets for future intervention against this deadly
      pathogen.

PMID- 18069892
TI  - The Legionella pneumophila IcmSW complex interacts with multiple Dot/Icm
      effectors to facilitate type IV translocation.
AB  - Many gram-negative pathogens use a type IV secretion system (T4SS) to deliver
      effector proteins into eukaryotic host cells. The fidelity of protein
      translocation depends on the efficient recognition of effector proteins by the
      T4SS. Legionella pneumophila delivers a large number of effector proteins into
      eukaryotic cells using the Dot/Icm T4SS. How the Dot/Icm system is able to
      recognize and control the delivery of effectors is poorly understood. Recent
      studies suggest that the IcmS and IcmW proteins interact to form a stable complex
      that facilitates translocation of effector proteins by the Dot/Icm system by an
      unknown mechanism. Here we demonstrate that the IcmSW complex is necessary for
      the productive translocation of multiple Dot/Icm effector proteins. Effector
      proteins that were able to bind IcmSW in vitro required icmS and icmW for
      efficient translocation into eukaryotic cells during L. pneumophila infection. We
      identified regions in the effector protein SidG involved in icmSW-dependent
      translocation. Although the full-length SidG protein was translocated by an icmSW
      dependent mechanism, deletion of amino terminal regions in the SidG protein
      resulted in icmSW-independent translocation, indicating that the IcmSW complex is
      not contributing directly to recognition of effector proteins by the Dot/Icm
      system. Biochemical and genetic studies showed that the IcmSW complex interacts
      with a central region of the SidG protein. The IcmSW interaction resulted in a
      conformational change in the SidG protein as determined by differences in
      protease sensitivity in vitro. These data suggest that IcmSW binding to effectors
      could enhance effector protein delivery by mediating a conformational change that
      facilitates T4SS recognition of a translocation domain located in the carboxyl
      region of the effector protein.

PMID- 18069893
TI  - Apicoplast lipoic acid protein ligase B is not essential for Plasmodium
      falciparum.
AB  - Lipoic acid (LA) is an essential cofactor of alpha-keto acid dehydrogenase
      complexes (KADHs) and the glycine cleavage system. In Plasmodium, LA is attached
      to the KADHs by organelle-specific lipoylation pathways. Biosynthesis of LA
      exclusively occurs in the apicoplast, comprising octanoyl-[acyl carrier protein]:
      protein N-octanoyltransferase (LipB) and LA synthase. Salvage of LA is
      mitochondrial and scavenged LA is ligated to the KADHs by LA protein ligase 1
      (LplA1). Both pathways are entirely independent, suggesting that both are likely
      to be essential for parasite survival. However, disruption of the LipB gene did
      not negatively affect parasite growth despite a drastic loss of LA (>90%).
      Surprisingly, the sole, apicoplast-located pyruvate dehydrogenase still showed
      lipoylation, suggesting that an alternative lipoylation pathway exists in this
      organelle. We provide evidence that this residual lipoylation is attributable to
      the dual targeted, functional lipoate protein ligase 2 (LplA2). Localisation
      studies show that LplA2 is present in both mitochondrion and apicoplast
      suggesting redundancy between the lipoic acid protein ligases in the erythrocytic
      stages of P. falciparum.

PMID- 18069894
TI  - A single mutation in chikungunya virus affects vector specificity and epidemic
      potential.
AB  - Chikungunya virus (CHIKV) is an emerging arbovirus associated with several recent
      large-scale epidemics. The 2005-2006 epidemic on Reunion island that resulted in
      approximately 266,000 human cases was associated with a strain of CHIKV with a
      mutation in the envelope protein gene (E1-A226V). To test the hypothesis that
      this mutation in the epidemic CHIKV (strain LR2006 OPY1) might influence fitness
      for different vector species, viral infectivity, dissemination, and transmission
      of CHIKV were compared in Aedes albopictus, the species implicated in the
      epidemic, and the recognized vector Ae. aegypti. Using viral infectious clones of
      the Reunion strain and a West African strain of CHIKV, into which either the E1
      226 A or V mutation was engineered, we demonstrated that the E1-A226V mutation
      was directly responsible for a significant increase in CHIKV infectivity for Ae.
      albopictus, and led to more efficient viral dissemination into mosquito secondary
      organs and transmission to suckling mice. This mutation caused a marginal
      decrease in CHIKV Ae. aegypti midgut infectivity, had no effect on viral
      dissemination, and was associated with a slight increase in transmission by Ae.
      aegypti to suckling mice in competition experiments. The effect of the E1-A226V
      mutation on cholesterol dependence of CHIKV was also analyzed, revealing an
      association between cholesterol dependence and increased fitness of CHIKV in Ae.
      albopictus. Our observation that a single amino acid substitution can influence
      vector specificity provides a plausible explanation of how this mutant virus
      caused an epidemic in a region lacking the typical vector. This has important
      implications with respect to how viruses may establish a transmission cycle when
      introduced into a new area. Due to the widespread distribution of Ae. albopictus,
      this mutation increases the potential for CHIKV to permanently extend its range
      into Europe and the Americas.

PMID- 18069895
TI  - The role of carcinine in signaling at the Drosophila photoreceptor synapse.
AB  - The Drosophila melanogaster photoreceptor cell has long served as a model system
      for researchers focusing on how animal sensory neurons receive information from
      their surroundings and translate this information into chemical and electrical
      messages. Electroretinograph (ERG) analysis of Drosophila mutants has helped to
      elucidate some of the genes involved in the visual transduction pathway
      downstream of the photoreceptor cell, and it is now clear that photoreceptor cell
      signaling is dependent upon the proper release and recycling of the
      neurotransmitter histamine. While the neurotransmitter transporters responsible
      for clearing histamine, and its metabolite carcinine, from the synaptic cleft
      have remained unknown, a strong candidate for a transporter of either substrate
      is the uncharacterized inebriated protein. The inebriated gene (ine) encodes a
      putative neurotransmitter transporter that has been localized to photoreceptor
      cells in Drosophila and mutations in ine result in an abnormal ERG phenotype in
      Drosophila. Loss-of-function mutations in ebony, a gene required for the
      synthesis of carcinine in Drosophila, suppress components of the mutant ine ERG
      phenotype, while loss-of-function mutations in tan, a gene necessary for the
      hydrolysis of carcinine in Drosophila, have no effect on the ERG phenotype in ine
      mutants. We also show that by feeding wild-type flies carcinine, we can duplicate
      components of mutant ine ERGs. Finally, we demonstrate that treatment with H(3)
      receptor agonists or inverse agonists rescue several components of the mutant ine
      ERG phenotype. Here, we provide pharmacological and genetic epistatic evidence
      that ine encodes a carcinine neurotransmitter transporter. We also speculate that
      the oscillations observed in mutant ine ERG traces are the result of the aberrant
      activity of a putative H(3) receptor.

PMID- 18069896
TI  - Localization of candidate regions maintaining a common polymorphic inversion
      (2La) in Anopheles gambiae.
AB  - Chromosomal inversion polymorphisms are thought to play a role in adaptive
      divergence, but the genes conferring adaptive benefits remain elusive. Here we
      study 2La, a common polymorphic inversion in the African malaria vector Anopheles
      gambiae. The frequency of 2La varies clinally and seasonally in a pattern
      suggesting response to selection for aridity tolerance. By hybridizing genomic
      DNA from individual mosquitoes to oligonucleotide microarrays, we obtained a
      complete map of differentiation across the A. gambiae genome. Comparing
      mosquitoes homozygous for the 2La gene arrangement or its alternative (2L+(a)),
      divergence was highest at loci within the rearranged region. In the 22 Mb
      included within alternative arrangements, two approximately 1.5 Mb regions near
      but not adjacent to the breakpoints were identified as being significantly
      diverged, a conclusion validated by targeted sequencing. The persistent
      association of both regions with the 2La arrangement is highly unlikely given
      known recombination rates across the inversion in 2La heterozygotes, thus
      implicating selection on genes underlying these regions as factors responsible
      for the maintenance of 2La. Polymorphism and divergence data are consistent with
      a model in which the inversion is maintained by migration-selection balance
      between multiple alleles inside these regions, but further experiments will be
      needed to fully distinguish between the epistasis (coadaptation) and local
      adaptation models for the maintenance of 2La.

PMID- 18069897
TI  - A RNA interference screen identifies the protein phosphatase 2A subunit PR55gamma
      as a stress-sensitive inhibitor of c-SRC.
AB  - Protein Phosphatase type 2A (PP2A) represents a family of holoenzyme complexes
      with diverse biological activities. Specific holoenzyme complexes are thought to
      be deregulated during oncogenic transformation and oncogene-induced signaling.
      Since most studies on the role of this phosphatase family have relied on the use
      of generic PP2A inhibitors, the contribution of individual PP2A holoenzyme
      complexes in PP2A-controlled signaling pathways is largely unclear. To gain
      insight into this, we have constructed a set of shRNA vectors targeting the
      individual PP2A regulatory subunits for suppression by RNA interference. Here, we
      identify PR55gamma and PR55delta as inhibitors of c-Jun NH(2)-terminal kinase
      (JNK) activation by UV irradiation. We show that PR55gamma binds c-SRC and
      modulates the phosphorylation of serine 12 of c-SRC, a residue we demonstrate to
      be required for JNK activation by c-SRC. We also find that the physical
      interaction between PR55gamma and c-SRC is sensitive to UV irradiation. Our data
      reveal a novel mechanism of c-SRC regulation whereby in response to stress c-SRC
      activity is regulated, at least in part, through loss of the interaction with its
      inhibitor, PR55gamma.

PMID- 18069900
TI  - The roles of complementary medicine in oncology.

PMID- 18069898
TI  - A mechanism misregulating p27 in tumors discovered in a functional genomic
      screen.
AB  - The cyclin-dependent kinase inhibitor p27(KIP1) is a tumor suppressor gene in
      mice, and loss of p27 protein is a negative prognostic indicator in human
      cancers. Unlike other tumor suppressors, the p27 gene is rarely mutated in
      tumors. Therefore misregulation of p27, rather than loss of the gene, is
      responsible for tumor-associated decreases in p27 protein levels. We performed a
      functional genomic screen in p27(+/-) mice to identify genes that regulate p27
      during lymphomagenesis. This study demonstrated that decreased p27 expression in
      tumors resulted from altered transcription of the p27 gene, and the retroviral
      tagging strategy enabled us to pinpoint relevant transcription factors. inhibitor
      of DNA binding 3 (Id3) was isolated and validated as a transcriptional repressor
      of p27. We further demonstrated that p27 was a downstream target of Id3 in src
      family kinase Lck-driven thymic lymphomagenesis and that p27 was an essential
      regulator of Lck-dependent thymic maturation during normal T-cell development.
      Thus, we have identified and characterized transcriptional repression of p27 by
      Id3 as a new mechanism decreasing p27 protein in tumors.

PMID- 18069899
TI  - Novel roles for selected genes in meiotic DNA processing.
AB  - High-throughput studies of the 6,200 genes of Saccharomyces cerevisiae have
      provided valuable data resources. However, these resources require a return to
      experimental analysis to test predictions. An in-silico screen, mining existing
      interaction, expression, localization, and phenotype datasets was developed with
      the aim of selecting minimally characterized genes involved in meiotic DNA
      processing. Based on our selection procedure, 81 deletion mutants were
      constructed and tested for phenotypic abnormalities. Eleven (13.6%) genes were
      identified to have novel roles in meiotic DNA processes including DNA
      replication, recombination, and chromosome segregation. In particular, this
      analysis showed that Def1, a protein that facilitates ubiquitination of RNA
      polymerase II as a response to DNA damage, is required for efficient synapsis
      between homologues and normal levels of crossover recombination during meiosis.
      These characteristics are shared by a group of proteins required for Zip1 loading
      (ZMM proteins). Additionally, Soh1/Med31, a subunit of the RNA pol II mediator
      complex, Bre5, a ubiquitin protease cofactor and an uncharacterized protein,
      Rmr1/Ygl250w, are required for normal levels of gene conversion events during
      meiosis. We show how existing datasets may be used to define gene sets enriched
      for specific roles and how these can be evaluated by experimental analysis.

PMID- 18069901
TI  - Psoriasis--pathophysiology, conventional, and alternative approaches to
      treatment.
AB  - Psoriasis is a common T-cell-mediated immune disorder characterized by
      circumscribed, red, thickened plaques with an overlying silver-white scale. It
      occurs worldwide, although the incidence is lower in warmer, sunnier climates.
      The primary cause of psoriasis is unknown. During an active disease state, an
      underlying inflammatory mechanism is frequently involved. Many conventional
      treatments focus on suppressing symptoms associated with psoriasis and have
      significant side effects. This article reviews several of the researched natural
      approaches to psoriasis treatment, while addressing its underlying cause.

PMID- 18069902
TI  - Active components and clinical applications of olive oil.
AB  - The olive tree, Olea europaea, is native to the Mediterranean basin and parts of
      Asia Minor. The fruit and compression-extracted oil have a wide range of
      therapeutic and culinary applications. Olive oil also constitutes a major
      component of the "Mediterranean diet." The chief active components of olive oil
      include oleic acid, phenolic constituents, and squalene. The main phenolics
      include hydroxytyrosol, tyrosol, and oleuropein, which occur in highest levels in
      virgin olive oil and have demonstrated antioxidant activity. Antioxidants are
      believed to be responsible for a number of olive oil's biological activities.
      Oleic acid, a monounsaturated fatty acid, has shown activity in cancer
      prevention, while squalene has also been identified as having anticancer effects.
      Olive oil consumption has benefit for colon and breast cancer prevention. The oil
      has been widely studied for its effects on coronary heart disease (CHD),
      specifically for its ability to reduce blood pressure and low-density lipoprotein
      (LDL) cholesterol. Antimicrobial activity of hydroxytyrosol, tyrosol, and
      oleuropein has been demonstrated against several strains of bacteria implicated
      in intestinal and respiratory infections. Although the majority of research has
      been conducted on the oil, consumption of whole olives might also confer health
      benefits.

PMID- 18069903
TI  - The plasma pharmacokinetics of R-(+)-lipoic acid administered as sodium R-(+)
      lipoate to healthy human subjects.
AB  - BACKGROUND: The racemic mixture, RS-(+/-)-alpha-lipoic acid (rac-LA) has been
      utilized clinically and in a variety of disease models. Rac-LA and the natural
      form, R-lipoic acid (RLA), are widely available as nutritional supplements,
      marketed as antioxidants. Rac-LA sodium salt (NaLA) or rac-LA potassium salt
      (KLA) has been used to improve the aqueous solubility of LA. STUDY RATIONALE:
      Several in vitro and animal models of aging and age-related diseases have
      demonstrated efficacy for the oral solutions of LA salts in normalizing age
      related changes to those of young animals. Other models and studies have
      demonstrated the superiority of RLA, the naturally occurring isomer over rac-LA.
      Despite this, RLA pharmacokinetics (PK) is not fully characterized in humans, and
      it is unknown whether the concentrations utilized in animal models can be
      achieved in vivo. Due to its tendency to polymerize, RLA is relatively unstable
      and suffers poor aqueous solubility, leading to poor absorption and low
      bioavailability. A preliminary study demonstrated the stability and
      bioavailability were improved by converting RLA to its sodium salt (NaRLA) and
      pre-dissolving it in water. The current study extends earlier findings from this
      laboratory and presents PK data for the 600-mg oral dosing of 12 healthy adult
      subjects given NaRLA. In addition, the effect of three consecutive doses was
      tested on a single subject relative to a one-time dosing in the same subject to
      determine whether plasma maximum concentration (Cmax) and the area under the
      plasma concentration versus time curve (AUC) values were comparable to those in
      animal studies and those achievable via intravenous infusions in humans. METHODS:
      Plasma RLA was separated from protein by a modification of a published method.
      Standard curves were generated from spiking known concentrations of RLA dissolved
      in ethanol and diluted in a phosphate-buffered saline (PBS) into each
      individual's baseline plasma to account for inter-individual differences in
      protein binding and to prevent denaturing of plasma proteins. Plasma RLA content
      was determined by the percent recovery using high-performance liquid
      chromatography (electrochemical/coulometric detection) (HPLC/ECD). RESULTS: As
      anticipated from the preliminary study, NaRLA is less prone to polymerization,
      completely soluble in water, and displays significantly higher Cmax and AUC
      values and decreased time to maximum concentration (Tmax) and T1/2 values than
      RLA or rac-LA. In order to significantly extend Cmax and AUC, it is possible to
      administer three 600-mg RLA doses (as NaRLA) at 15-minute intervals to achieve
      plasma concentrations similar to those from a slow (20-minute) infusion of LA.
      This is the first study to report negligible unbound RLA even at the highest
      achievable plasma concentrations.

PMID- 18069904
TI  - XP-828L in the treatment of mild to moderate psoriasis: randomized, double-blind,
      placebo-controlled study.
AB  - BACKGROUND: XP-828L, a protein extract obtained from sweet whey, has demonstrated
      potential benefit for the treatment of mild to moderate psoriasis in an open
      label study. OBJECTIVE: To study in a randomized, double-blind, placebo
      controlled study the safety and efficacy of XP-828L in the treatment of mild to
      moderate psoriasis. DESIGN: XP-828L 5 g/d (group A, n=42) or placebo (group B,
      n=42) was given orally for 56 days followed by XP-828L 5 g/d in group A and by XP
      828L 10 g/d in group B for an additional 56 days. RESULTS: Patients receiving XP
      828L 5 g/d for 56 days had an improved Physician's Global Assessment (PGA) score
      compared with patients under placebo (p less than 0.05). Considering the data of
      group A only, the PGA score improved from day 1 to day 56 (p less than 0.01); the
      Psoriasis Area and Severity Index score improved as well, but to a lesser extent
      (p less than 0.05). CONCLUSION: Oral administration of 5 g/d XP-828L compared
      with a placebo significantly improved the PGA score of patients with mild to
      moderate psoriasis.

PMID- 18069905
TI  - Momordica charantia (bitter melon). Monograph.

PMID- 18069906
TI  - L-tyrosine. Monograph.

PMID- 18069907
TI  - The accidental mentor: Australian rural nurses developing supportive
      relationships in the workplace.
AB  - INTRODUCTION: Like the fictional 'Accidental Tourist', an author who does not
      plan to write about travel, the accidental mentor is an experienced rural nurse
      who does not plan to be a mentor, and yet assumes that role with new or novice
      rural nurses as a result of them encountering a critical incident. Accidental
      mentoring is a short-term relationship that provides support for the new or
      novice nurse in managing the incident, while maintaining their level of
      confidence. This article describes the findings from a constructivist grounded
      theory study that examined Australian rural nurses' experiences of mentoring,
      including evidence for a new concept of mentoring - accidental mentoring.
      METHODS: Constructivist grounded theory is a research methodology that focuses on
      issues of importance for participants around an area of common interest - in this
      case Australian rural nurse mentoring. In this study, seven participants were
      interviewed, generating nine transcripts. These were analysed using a process of
      concurrent data generation and analysis. In addition, the literature regarding
      rural nurse workforce and mentoring was incorporated as a source of data, using
      collective frame analysis. RESULTS: Rural nurses live their work, which
      predisposes them to developing supportive relationships with new or novice rural
      nurses. Supportive relationships range from preceptoring, to accidental
      mentoring, mentoring and deep friendship, depending on the level of trust and
      engagement that is established between the partners and the amount of time they
      spend together. Accidental mentoring is a short-term relationship that is
      prompted by experienced rural nurses observing a new or novice rural nurse
      experiencing a critical incident. CONCLUSIONS: Findings are presented that
      illustrate a new concept of accidental mentoring not present in the current
      literature around nurse mentoring. A series of recommendations are included that
      suggest strategies for improved rural nurse retention as an outcome of
      recognising and developing such supportive relationships in the workplace.
      Strategies include: performance review and development processes that account for
      all forms of supportive relationships conducted in the workplace; recognising the
      importance of developing supportive relationships and allocating time for these;
      and continuing professional development designed to meet local needs for
      developing a culture of support in the workplace.

PMID- 18069908
TI  - Time allocation and caseload capacity in telephone depression care management.
AB  - OBJECTIVE: To document time allocated to care management activities and care
      manager workload capacity using data collected for studies of telephone care
      management of depression. STUDY DESIGN: Cross-sectional, descriptive analysis of
      depression care manager (DCM) activities and workload in 2 collaborative
      depression care interventions (1 implementation study and 1 effectiveness study)
      at Department of Veterans Affairs primary care facilities. METHODS: Each
      intervention tracked specific care management activities for 4 weeks, recording
      the number of events for each activity type and length of time for each activity.
      Patient workload data were obtained from the patient tracking systems for the 2
      projects. We calculated the average time for each activity type, the average
      total time required to complete an initial assessment call and follow-up call,
      and the maximum patient panel for both projects. RESULTS: The total time per
      successful initial assessment was 75 to 95 minutes, and the total time per
      successful follow-up call was 51 to 60 minutes, with more time spent on ancillary
      activities (precall preparation, postcall documentation, and provider
      communication) than on direct patient contact. A significant amount of time was
      spent in unsuccessful call attempts, requiring 9 to 11 minutes for each attempt.
      The maximum panel size per care manager per quarter was in the range of 143 to
      165 patients. CONCLUSIONS: The study found similar DCM time allocations and panel
      sizes across 2 studies and 3 regions with full-time DCMs. Reductions in DCM time
      spent on ancillary activities may be achievable through improved informatics and
      other support for panel management.

PMID- 18069909
TI  - Validity of the Asthma Control Test completed at home.
AB  - OBJECTIVE: To provide additional validity data for the Asthma Control TestTM
      (ACT) using a different criterion measure, setting, and population. STUDY DESIGN:
      Cross-sectional survey. METHODS: Questionnaires were completed at home by a
      random sample of 570 members of a large integrated healthcare organization who
      were 35 years or older with utilization suggestive of active asthma. The
      questionnaires included the ACT; another validated asthma control questionnaire
      (Asthma Therapy Assessment Questionnaire [ATAQ]), which was used as the criterion
      measure; a validated quality-of-life tool (Mini Asthma Quality of Life
      Questionnaire [Mini-AQLQ]); a validated symptom frequency scale (Asthma Outcomes
      Monitoring System); and information regarding demographics. RESULTS: The ACT
      score was statistically significantly correlated with findings on the ATAQ (P = 
      0.73), Mini-AQLQ (P = 0.77), and symptom frequency scale (P = -0.69). The optimal
      ACT cutoff for well-controlled asthma (ATAQ level, 0) was confirmed to be 20 or
      higher (sensitivity, 78.1%; specificity, 83.8%), and the optimal ACT cutoff for
      poorly controlled asthma (ATAQ level, 3-4) was confirmed to be 15 or lower
      (sensitivity, 90.4%; specificity, 80.9%). CONCLUSION: These data further support
      the validity of the ACT in the home setting among a random sample of patients
      with asthma.

PMID- 18069910
TI  - Evidence for the effect of disease management: is $1 billion a year a good
      investment?
AB  - OBJECTIVE: To assess the evidence for the effect of disease management on quality
      of care, disease control, and cost, with a focus on population-based programs.
      STUDY DESIGN: Literature review. METHODS: We conducted a literature search for
      and a structured review of studies on population-based disease management
      programs, as well as for reviews and meta-analyses of disease management
      interventions. We identified 3 evaluations of large-scale population-based
      programs, as well as 10 meta-analyses and 16 systematic reviews, covering 317
      unique studies. RESULTS: We found consistent evidence that disease management
      improves processes of care and disease control but no conclusive support for its
      effect on health outcomes. Overall, disease management does not seem to affect
      utilization except for a reduction in hospitalization rates among patients with
      congestive heart failure and an increase in outpatient care and prescription drug
      use among patients with depression. When the costs of the intervention were
      appropriately accounted for and subtracted from any savings, there was no
      conclusive evidence that disease management leads to a net reduction of direct
      medical costs. CONCLUSIONS: Although disease management seems to improve quality
      of care, its effect on cost is uncertain. Most of the evidence to date addresses
      small-scale programs targeting high-risk individuals, while only 3 studies
      evaluate large population-based interventions, implying that little is known
      about their effect. Payers and policy makers should remain skeptical about vendor
      claims and should demand supporting evidence based on transparent and
      scientifically sound methods.

PMID- 18069911
TI  - Voluntary disenrollment from Medicare advantage plans: valuable signals of market
      performance.
AB  - OBJECTIVE: To examine 2000-2005 trends in the reasons Medicare beneficiaries gave
      for disenrolling from their Medicare Advantage (MA) plans. STUDY DESIGN: We used
      data from 6 consecutive years of Consumer Assessment of Health Plans surveys,
      which asked about 33 possible reasons for disenrollment, including problems with
      plan information, out-of-pocket costs, plan benefits, and coverage. Respondents
      numbered more than 50,000 beneficiaries each year from a variety of MA plan types
      providing full Medicare benefits in place of traditional fee-for-service
      Medicare. The survey also collected demographic and health status information.
      METHODS: We classified reasons for disenrollment into 2 key groups: (1) reasons
      related to plan information and (2) reasons related to cost/benefits problems. We
      examined whether disparities existed between vulnerable and less vulnerable
      populations that might reflect different experiences by these groups over time.
      RESULTS: Disparities between vulnerable and less vulnerable groups were present
      but generally diminished over time as competition intensified, with noticeable
      differences between African American and Hispanic subpopulations regarding
      problems with plan information. CONCLUSIONS: The premise of the Medicare
      Prescription Drug, Improvement, and Modernization Act of 2003 was that more plans
      would increase competition, resulting in higher-quality healthcare services.
      However, an increased number of plan choices complicates the health plan decision
      making process for beneficiaries. With further expansion of plans and choices
      following implementation of Part D, efforts must continue to direct informational
      materials to all beneficiaries, particularly those in vulnerable subgroups. More
      help in interpreting the information may be required to maximize consumer
      benefits.

PMID- 18069912
TI  - Patient access and clinical efficiency improvement in a resident hospital-based
      women's medicine center clinic.
AB  - OBJECTIVES: To apply the Six Sigma tools of Change Acceleration Process and Work
      Out and to improve patient access in an outpatient clinic in a hospital-based
      residency training program. STUDY DESIGN: Observational study. METHODS:
      Comparison of productivity in an obstetrics and gynecology clinic after
      implementation of the Six Sigma principles, with a comparable internal medicine
      clinic as a control group. Productivity from January 1 through December 31, 2005,
      was assessed in both clinics. After applying the Six Sigma tools to obstetrics
      and gynecology, outputs from both clinics from January 1 through December 31,
      2006, were analyzed. RESULTS: Wait times for new obstetrical visits decreased
      from 38 to 8 days. The patient time spent in the clinic dropped from 3.2 to 1.5
      hours. Initial gynecologic visits increased by 87% (from 453 to 850 per year),
      return gynecologic visits increased by 66% (from 1392 to 2311 per year), initial
      obstetrical visits increased by 55% (from 520 to 808 per year), repeat
      obstetrical visits increased by 45% (from 2239 to 3243 per year), and the mean
      patient satisfaction scores increased from 5.75 to 8.54 (on a 10-point scale).
      The gross clinic revenue increased by 73% in the first 6 months of 2006 over that
      of the previous year. By contrast, internal medicine patient wait times for new
      patients and for revisits, patient satisfaction scores, total number of clinic
      visits, and revenues remained unchanged. CONCLUSION: Application of the Six Sigma
      principles resulted in a team approach to solving the clinic's productivity
      issues.

PMID- 18069913
TI  - A "follow the energy" approach for astrobiology.

PMID- 18069915
TI  - Xenogenic transfer of isolated murine mitochondria into human rho0 cells can
      improve respiratory function.
AB  - Mitochondrial DNA mutations are the direct cause of several physiological
      disorders and are also associated with the aging process. The modest progress
      made over the past two decades towards manipulating the mitochondrial genome and
      understanding its function within living mammalian cells means that cures for
      mitochondrial DNA mutations are still elusive. Here, we report that transformed
      mammalian cells internalize exogenous isolated mitochondria upon simple co
      incubation. We first demonstrate the physical presence of internalized
      mitochondria within recipient cells using fluorescence microscopy. Second, we
      show that xenogenic transfer of murine mitochondria into human cells lacking
      functional mitochondria can functionally restore respiration in cells lacking
      mtDNA. Third, utilizing the natural competence of isolated mitochondria to take
      up linear DNA molecules, we demonstrate the feasibility of using cellular
      internalization of isolated exogenous mitochondria as a potential tool for
      studying mitochondrial genetics in living mammalian cells.

PMID- 18069916
TI  - Exercise training promotes SIRT1 activity in aged rats.
AB  - The objective of this study was to determine the effects of aging and exercise
      training on SIRT1 activity and to identify a pathway linking SIRT1 to antioxidant
      response and cell cycle regulation in rats. SIRT1 is a NAD(+)-dependent
      deacetylase involved in the oxidative stress response and aging. The effects of
      aging and of moderate and prolonged exercise training in rats are unknown. We
      measured SIRT1 activity in heart and adipose tissue of young (6 months old),
      sedentary old (24 months), and trained old (24 months) rats using an assay kit.
      Peroxidative damage was determined by measuring levels of thiobarbituric reactive
      substances (TBARS) and the protein-aldehyde adduct 4-hydroxynonenal (4-HNE).
      MnSOD, catalase, and FOXO3a levels were evaluated by Western blot, and GADD45a,
      cyclin D(2), and FOXO3a mRNA by RT-PCR. Aging significantly reduced SIRT1
      activity in heart, but not in adipose tissue, increased TBARS and 4-HNE and
      decreased Mn-SOD and catalase expression in both heart and adipose tissue. Aging
      did not affect FOXO3a protein expression in the heart or FOXO3a mRNA in adipose
      tissue. Exercise training significantly increased FOXO3a protein in the heart and
      FOXO3a mRNA in adipose tissue of aged rats. It also significantly increased Mn
      SOD and catalase levels in both heart and adipose tissue. The exercise-induced
      increase in SIRT1 activity in the heart caused a decrease in cyclin D(2) and an
      increase in GADD45a mRNA expression. There was a similar decrease in cyclin D(2),
      and no changes in GADD45a mRNA expression in adipose tissue. We concluded that
      exercise training, which significantly increases SIRT1 activity, could counteract
      age-related systems impairment.

PMID- 18069917
TI  - The effects of TeleWound management on use of service and financial outcomes.
AB  - This study investigated the effects of a TeleWound program on the use of service
      and financial outcomes among homebound patients with chronic wounds. The
      TeleWound program consisted of a Web-based transmission of digital photographs
      together with a clinical protocol. It enabled homebound patients with chronic
      pressure ulcers to be monitored remotely by a plastic surgeon. Chronic wounds are
      highly prevalent among chronically ill patients in the United States (U.S.).
      About 5 million chronically ill patients in the U.S. have chronic wounds, and the
      aggregate cost of their care exceeds $20 billion annually. Although 25% of home
      care referrals in the U.S. are for wounds, less than 0.2% of the registered
      nurses in the U.S. are wound care certified. This implies that the majority of
      patients with chronic wounds may not be receiving optimal care in their home
      environments. We hypothesized that TeleWound management would reduce visits to
      the emergency department (ED), hospitalization, length of stay, and visit acuity.
      Hence, it would improve financial performance for the hospital. A quasi
      experimental design was used. A sample of 19 patients receiving this intervention
      was observed prospectively for 2 years. This was matched to a historical control
      group of an additional 19 patients from hospital records. Findings from the study
      revealed that TeleWound patients had fewer ED visits, fewer hospitalizations, and
      shorter length of stay, as compared to the control group. Overall, they
      encumbered lower cost. The results of this clinical study are striking and
      provide strong encouragement that a single provider can affect positive clinical
      and financial outcomes using a telemedicine wound care program. TeleWound was
      found to be a credible modality to manage pressure ulcers at lower cost and
      possibly better health outcomes. The next step in this process is to integrate
      the model into daily practice at bellwether medical centers to determine
      programmatic effectiveness in larger clinical arenas.

PMID- 18069919
TI  - Multi-locular thymic cysts after acute pancreatitis in a liver transplant
      recipient.

PMID- 18069918
TI  - Efficacy and safety of intravenous iron therapy as an alternative/adjunct to
      allogeneic blood transfusion.
AB  - Anaemia is a common condition among patients admitted to hospital medicosurgical
      departments, as well as in critically ill patients. Anaemia is more frequently
      due to absolute iron deficiency (e.g. chronic blood loss) or functional iron
      deficiency (e.g. chronic inflammatory states), with other causes being less
      frequent. In addition, preoperative anaemia is one of the major predictive
      factors for perioperative blood transfusion. In surgical patients, postoperative
      anaemia is mainly caused by perioperative blood loss, and it might be aggravated
      by inflammation-induced inhibition of erythropoietin and functional iron
      deficiency (a condition that cannot be corrected by the administration of oral
      iron). All these mechanisms may be involved in the anaemia of the critically ill.
      Intravenous iron administration seems to be safe, as very few severe side-effects
      were observed, and may result in hastened recovery from anaemia and lower
      transfusion requirements. However, it is noteworthy that many of the
      recommendations given for intravenous iron treatment are not supported by a high
      level of evidence and this must be borne in mind when making decisions regarding
      its application to a particular patient. Nonetheless, this also indicates the
      need for further large, randomized controlled trials on the safety and efficacy
      of intravenous iron for the treatment of anaemia in different clinical settings.

PMID- 18069920
TI  - Biliary complications in right lateral sector graft live donor liver
      transplantation.
AB  - Biliary complications remain the most challenging issue in adult living donor
      liver transplantation (LDLT) and to the best of our knowledge, no study has
      focused on the biliary complications in LDLT with right lateral sector graft
      (RLSG), a graft consisting of segments VI and VII according to Couinaud's
      nomenclature for liver segmentation. Between January 1996 and October 2006, 310
      LDLTs were performed for adult recipients at our institution. Among them, 20
      patients received RLSG. The incidence of biliary complications during follow-up
      in these patients with RLSG was retrospectively analyzed. Follow-up period after
      transplantation ranged from 1 to 87 months (median 58 months). The 3-year and 5
      year graft survival rates following the use of RLSGs in LDLT were 90% and 90%,
      respectively. Biliary complications were encountered in altogether nine patients.
      Two patients (10%) were complicated with bile leakage requiring surgical
      intervention. Seven patients (35%) were complicated with bile duct stenosis,
      which occurred with a median interval of 26 months (range: 6-51 months) after
      LDLT. Four were treated surgically and the other three were treated by endoscopic
      approach. Outcomes of the interventions were satisfactory in all cases. The
      incidence and severity of biliary complications after LDLT using RLSG was within
      an acceptable range with excellent graft survival. Accordingly, it is concluded
      that RLSG is a technically feasible option that may effectively expand the donor
      pool. Further application of RLSG is warranted.

PMID- 18069921
TI  - Do we have the same clinical results with Neoral and Equoral treatment in kidney
      transplant recipients? A pilot study.

PMID- 18069922
TI  - Immunosuppression and tumor development in organ transplant recipients: the
      emerging dualistic role of rapamycin.
AB  - Cancer morbidity and mortality are increasingly apparent risks in transplant
      recipients, thus reducing life quality and overall survival. These risks have
      largely been attributed to long-term immunosuppressive drug therapy, which
      remains necessary to prevent organ allograft rejection. Interestingly, however,
      recent studies challenge the premise that all immunosuppressive drugs necessarily
      promote cancer. A particular class of immunosuppressants, referred to as
      mammalian target of rapamycin (mTOR) inhibitors, has been shown to have potent
      anti-cancer effects that are presently being tested in clinical studies. The
      focus of this review is to present current evidence that allows us to understand
      better the dual immunosuppressive and anti-cancer functions of this class of
      drugs used to prevent allograft rejection. We will concentrate on the different
      functions of mTOR that allow it to simultaneously control the immune system and
      tumor development. We will also discuss results from current clinical studies
      that either support or refute this potential dualistic role.

PMID- 18069923
TI  - Nonsurgical policy for treatment of bilioenteric anastomotic stricture after
      living donor liver transplantation.
AB  - Biliary complications remain a significant cause of morbidity following living
      donor liver transplantation. The purpose of this retrospective study was to
      assess the outcome of nonsurgical management for hepatojejunostomy stricture in
      our institution. We reviewed 22 patients with hepatojejunostomy stricture among
      the 231 patients who underwent living donor liver transplantation between June
      1990 and December 2005. Hepatojejunostomy stricture was confirmed by percutaneous
      transhepatic or endoscopic retrograde cholangiography. Anastomotic strictures
      were treated by balloon dilatation. Percutaneous transhepatic cholangiography was
      performed on 15 of the 22 patients. Two of 15 patients, with complete obstruction
      of the anastomosis, were treated successfully by Yamanouchi magnet compression
      anastomosis. Although another two patients died of infectious disease that was
      unlikely to have been related to biliary complications, anastomotic patency was
      maintained in the other 13 patients. Endoscopic retrograde cholangiography was
      performed on seven of the 22 patients. None of the 22 patients required re
      operation or died of biliary complications. The 5-year graft survival rate of
      85.6% in the 22 patients with stricture was equivalent to that of the patients
      without stricture (82.9%, P = 0.98). Advances in intervention techniques have
      enabled wider application of nonsurgical approaches for this complication, and
      fair results have been obtained.

PMID- 18069924
TI  - Treatment of central pontine myelinolysis with plasmapheresis and immunoglobulins
      in liver transplant patient.

PMID- 18069925
TI  - Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion
      injury in rat.
AB  - Ischemic postconditioning is a phenomenon that intermittent interruptions of
      blood flow in the early phase of reperfusion can protect organ from
      ischemia/reperfusion (I/R) injury. In the present study, we investigated whether
      the protective effect of ischemic postconditioning was associated with modulation
      of apoptosis after renal I/R injury. Rats were subjected to 45 min of renal
      ischemia, both with and without treatment with ischemic postconditioning. Serum
      urea nitrogen and creatinine levels, phosphorylation of Akt and ERK1/2 and
      apoptosis were compared after renal injury. Our data showed that ischemic
      postconditioning attenuated the renal dysfunction and cell apoptosis induced by
      I/R and increased phosphorylation of Akt and ERK1/2. The results indicated that
      ischemic postconditioning decreased apoptosis and improved renal function. This
      protective effect may be related with the levels of Akt and ERK1/2 activation.
      These findings may have major implications in the treatment of renal
      transplantation.

PMID- 18069926
TI  - Pulmonary hemodynamics as predictors of mortality in patients awaiting lung
      transplantation.
AB  - Lung transplantation (LTx) is a therapeutic option for patients with end-stage
      lung disease. However, the mortality rate of patients on the waiting list is
      high. The purpose of this study was to examine the prognostic value of cardio
      pulmonary hemodynamics for death in patients awaiting LTx. Retrospectively, 177
      patients with advanced lung disease accepted for LTx at Sahlgrenska University
      Hospital from January 1990 through December 2003 were studied. Patient
      demographics, pulmonary function tests, gas exchange and hemodynamic variables
      were included in the analysis. Death while awaiting LTx was the primary endpoint
      for all analyses. Mean age was 49 +/- 9 years. Main diagnoses were alpha 1
      antitrypsin deficiency (n = 56), chronic obstructive pulmonary disease (n = 61),
      cystic fibrosis (n = 14) and interstitial lung disease (n = 46). Thirty patients
      died (17%). LTx was performed in 143 cases. By univariate analyses, forced vital
      capacity (FVC) % of predicted, pulmonary vascular resistance (PVR) and diagnosis
      were associated with risk for death. In multivariate analysis PVR (HR, 1.22; 95%
      CI, 1.06-1.41; P = 0.006) and FVC% of predicted (HR, 0.97; 95% CI, 0.94-0.99; P =
      0.01) were independently associated with death. Patients with increased PVR and a
      lower FVC % of predicted awaiting LTx should be considered for a higher organ
      allocation priority. Assessment of pulmonary hemodynamics needs to be considered
      during evaluation for LTx.

PMID- 18069927
TI  - Renal allograft biopsies in the era of C4d staining: the need for change in the
      Banff classification system.
AB  - C4d immunostaining in the peritubular capillaries (PTC) is a marker of antibody
      mediated rejection (AMR). We evaluated the histopathologic diagnoses of 388 renal
      transplant biopsies since the implementation of routine C4d immunostaining at our
      center. Of these, 155 (40%) biopsies had evidence of acute cellular rejection
      (ACR), out of which 119 (77%) had pure ACR, 31 (20%) had ACR with concomitant
      features of AMR, and five (3%) had ACR with focal C4d staining. Sixty-four (16%)
      biopsies exhibited features of AMR [33 (52%) pure AMR, and 31(48%) concomitant
      AMR and ACR]. One hundred and fifty-five (40%) biopsies had features of
      interstitial fibrosis and tubular atrophy (IFTA). Of these, 20 (13%) had
      concomitant AMR [13 (8.5%) had pure AMR and seven (4.5%) had concomitant ACR and
      AMR]. Creatinine at the time of biopsy was higher in patients with mixed ACR and
      AMR and the clinical behavior of mixed lesions is more aggressive over time.
      Despite having a lower serum creatinine at the time of biopsy, patients with IFTA
      experienced gradual decline in graft function over time. The pathologic findings
      in renal allograft biopsies are often mixed and mixed lesions appear to have more
      aggressive clinical behavior. These findings suggest the need for change in the
      Banff classification system to better capture the complexity of renal allograft
      pathologies.

PMID- 18069928
TI  - Transfer of tolerance to heart and kidney allografts in the rat model.
AB  - Long-term allograft acceptance can be induced in the rat using a variety of
      maneuvers. One of the cardinal features of some models of tolerance is that once
      the tolerance state has been established, it can be perpetuated to naive
      recipients by the adoptive transfer of donor-specific regulatory cells. Such
      adoptive transfer studies have also addressed the capacity of T-cell
      subpopulations and non-T cells to transfer tolerance. However, tolerance cannot
      be transferred in all models. The underlying reasons for this are unclear with
      some studies pointing towards dose-dependent aspects and timing of expansion of T
      regulatory cells following tolerance transfer. Further exploration of this
      phenomenon will help us to understand better the mechanisms upon which allograft
      tolerance is based, and will provide new perspectives for further experimental
      studies.

PMID- 18069929
TI  - Payment for whole blood donations in Lithuania: the risk for infectious disease
      markers.
AB  - BACKGROUND AND OBJECTIVES: In Lithuania, remuneration for whole blood donations
      still prevails, with the government covering payment for the donors. The payment
      per donation in cash is equal to 40 litas (euro11.6); it is offered to all blood
      donors and accepted by the majority of them. Donors who gave blood and received
      the payment are treated as remunerated donors; those who gave blood and did not
      take the payment are treated as non-remunerated ones. The purpose of this study
      was to assess the risk of payment for whole blood donations and to analyse the
      prevalence of infectious diseases markers per 100 remunerated and non
      remunerated, first-time and regular whole blood donations, and to compare the
      risk ratios of infectious disease markers of remunerated and non-remunerated
      whole blood donations in 2005 and 2006 at the National Blood Center in Lithuania.
      MATERIALS AND METHODS: Whole blood donors were categorized as follows: (i) first
      time donor, remunerated; (ii) first-time donor, non-remunerated; (iii) regular
      donor, remunerated; and (iv) regular donor, non-remunerated. The blood donations
      were analysed for the presence or absence of the following infectious disease
      markers: anti-hepatitis C virus (anti-HCV), hepatitis B surface antigen (HBsAg),
      anti-human immunodeficiency virus (anti-HIV (1)/(2)) and syphilis. Only confirmed
      infectious disease markers were classified. To assess the risk of payment for
      whole blood donations, the prevalence of infectious disease markers per 100
      donations in the different donor groups and the risk ratios between the
      remunerated and non-remunerated donations were determined. RESULTS: The
      prevalence per 100 first-time remunerated donations was: for anti-HCV 1.84 (2005)
      and 2.98 (2006); for HBsAg 1.73 (2005) and 2.03 (2006); for syphilis 0.67 (2005)
      and 1.03 (2006). The prevalence per 100 first-time non-remunerated donations was:
      for anti-HCV 0.93 (2005) and 0.98 (2006); for HBsAg 1.57 (2005) and 1.33 (2006);
      for syphilis 0.29 (2005) and 0.47 (2006). The first-time donors who were
      remunerated for whole blood donations had a significantly higher prevalence of
      infectious disease markers per 100 donations and a higher risk ratio for at least
      three infectious disease markers (HBsAg, anti-HCV and syphilis) as compared to
      first-time donors who were non-remunerated. The regular donors who were non
      remunerated for whole blood donations had the lowest prevalence of all infectious
      disease markers: anti-HCV -0.03 (2005) and 0.04 (2005); syphilis -0.06 (2005) and
      0.02 (2006); and any positive cases of HBsAg and anti-HIV (1)/(2) were found both
      in 2005 and 2006. No statistically significance differences in incidence and risk
      ratio existed when comparing the regular donations who were remunerated and non
      remunerated. CONCLUSION: The payment for whole blood donors provides a higher
      risk for infectious disease markers of first-time donations at the National Blood
      Center in Lithuania.

PMID- 18069930
TI  - Primary gastrointestinal aspergillosis after autologous peripheral blood
      progenitor cell transplantation: an unusual presentation of invasive
      aspergillosis.
AB  - Primary gastrointestinal invasive aspergillosis is an unusual presentation in
      patients with malignancies undergoing chemotherapy. Visceral organ involvement
      with Aspergillus sp. most often occurs in the setting of disseminated infection.
      We report a case of a patient diagnosed with Wilms' tumor who developed primary
      gastrointestinal aspergillosis after autologous peripheral blood progenitor cell
      transplantation. He had no evidence of pulmonary, sinus, or central nervous
      system infection. The patient died of septic shock after emergency surgery.

PMID- 18069931
TI  - Hepatic gas gangrene following orthotopic liver transplantation: three cases
      treated with re-transplantation and a review of the literature.
AB  - Gas gangrene is a rare and devastating infectious process that can occur after
      liver transplantation, most often following hepatic artery thrombosis. We here
      report 3 cases of gas gangrene following orthotopic liver transplantation. Blood
      cultures were positive for Clostridium clostridiiforme in one case. In 2 other
      cases liver tissue from explanted specimens was positive for Enterobacter
      cloacae. Ultrasound demonstrated hepatic artery thrombosis and computed
      tomography imaging revealed diffuse liver necrosis with gas formation in each
      case. All 3 patients were successfully treated with a combination of antibiotics
      and emergent re-transplantation. We review previously published cases of gas
      gangrene after liver transplant and emphasize the importance of hepatic artery
      thrombosis in the development of this syndrome as well as the frequent
      involvement of non-clostridial organisms. Early diagnosis and aggressive combined
      medical and surgical treatment including re-transplantation are essential for
      successful treatment of these rare and catastrophic infections.

PMID- 18069932
TI  - Identification of the novel HLA-C allele Cw*0751.
AB  - We report the novel HLA-Cw allele HLA-Cw*0751. The allele was identified during
      routine sequence-based typing in our laboratory. The novel allele is identical to
      Cw*07020101 except for a single nucleotide change in codon 90.2 in position 268.
      HLA-Cw*0751 allele possesses an adenine at position 268 in exon 2, while HLA
      Cw*07020101 has a cytosine at this position. Although this substitution does not
      change serologic reactivity of HLA-Cw7 molecule, it changes the amino acid at
      codon 90 from an aspartic acid to an alanine. Aspartic acid is polar and acidic,
      while alanine is non-polar and neutral.

PMID- 18069933
TI  - Sequencing of a novel HLA-DRB1*07 allele with a new polymorphism at amino acid
      position 21 (DRB1*0715).
AB  - DRB1*0715 differs from DRB1*070101 in a point nucleotide mutation at codon 21
      (ACG-->AAG), which produces an amino acid residue change from T to K.

PMID- 18069934
TI  - Thirty-two novel HLA-A alleles identified during intermediate resolution testing.
AB  - Thirty-two novel human leukocyte antigen-A alleles are described: four A*01
      (*0110, *0112, *0113 and *0117), four A*02 (*0263, *0280, *0292 and *9201), two
      A*03 (*0316 and *0325), four A*11 (*111502, *1117, *1122 and *1123), five A*24
      (*2441, *2450, *2455, *2456 and *2457), one A*26 (*2627), two A*29 (*2909 and
      *2914), two A*30 (*3013 and *3016), one A*32 (A*3213), two A*34 (*3407 and *3408)
      and five A*68 (*6828, *6829, *6830, *6831 and *6834). Seventeen of the variants
      are single-nucleotide substitutions from their most homologous allele, which
      results in amino acid changes (A*0117, *0263, *0292, *0316, *0325, *1122, *1123,
      *2455, *2456, *2457, *2627, *2909, *3016, *3407, *6828, *6831 and *6834), and
      only one is silent substitution (A*111502). The remaining alleles differ from
      their most similar alleles by two to six nucleotide substitutions.

PMID- 18069935
TI  - The sodium-dependent glucose cotransporter SLC5A11 as an autoimmune modifier gene
      in SLE.
AB  - Genetic studies in several human autoimmune diseases suggest that the
      pericentromeric region of chromosome 16 might harbor an autoimmune modifier gene.
      We hypothesized that the sodium-dependent glucose cotransporter gene SLC5A11 is
      such a gene, and so might interact with immune-related genes. Herein, this
      hypothesis was tested in a genetic evaluation of the multiple gene effect in
      systemic lupus erythematosus (SLE). We used the case-control candidate gene
      association approach. Eight immune-related genes involved in inflammation and
      autoantibody generation and clear-up [interleukin 1 receptor antagonist (IL1RN),
      interleukin 1-beta (IL1-beta), tumor necrosis factor-alpha (TNF-alpha),
      lymphotoxin-alpha (LTA), tumor necrosis factor ligand superfamily, member 6
      (TNFSF6), programmed cell death 1 (PDCD1), C2, and complement component 4 (C4)]
      were selected for study. Frequency of each candidate's genotype and allele
      between case and control were compared. Results were stratified by reanalyzing
      genotype data with relevant symptoms. Finally, improved computational data mining
      was used to analyze the phenotypes in a large data set. In the frequency
      analysis, only IL1-beta was significantly associated with SLE. Stratification
      analysis showed a significant association with SLE symptoms between SLC5A11 and
      the other immune-related genes, with the exceptions of TNFSF6 and C4. SLC5A11 was
      significantly associated with low C4 (as was TNF-alpha), anti-Smith antibody
      (anti-Sm) (as was C2), serositis, and alopecia. Finally, SLC5A11 interacted with
      PDCD1, TNF-alpha, LTA, and C4. After our study, we concluded that SLC5A11 is
      involved with some immune effects and interacts with immune-related gene(s),
      consistent with its function as an autoimmune modifier gene. Furthermore, SLC5A11
      might induce apoptosis through the TNF-alpha, PDCD1 pathway. The present genotype
      phenotype mapping approach should be applicable to genetic study of other complex
      diseases.

PMID- 18069936
TI  - Killer immunoglobulin receptor gene and allele frequencies in Caucasoid, Oriental
      and Black populations from different continents.
AB  - Parallel to the growth in interest in the past few years in the killer
      immunoglobulin-like receptor (KIR) genes has been the elucidation of the
      presence/absence of these genes and to a very limited extent, the frequency of
      alleles of these genes in many populations. In the present study, we have chosen
      seven populations to investigate the presence/absence of the KIR genes and their
      alleles, i.e. Cuban, Brazilian, Oman, Hong Kong Chinese, Singapore Chinese, South
      African Xhosa and South African San. The populations were chosen to represent
      different continents of the world. We show the divergence in the frequencies of
      these genes, and their alleles, in the different populations. Many new sequence
      specific oligonucleotide probe patterns represent new alleles, each occurred in
      only one of the populations. The KIR gene frequencies of these seven populations
      were calculated and genetic distances were represented by neighbour-joining
      dendrograms and correspondence analyses. Also, the presence or absence of 17 KIR
      loci in the presently studied populations was compared with the presence or
      absence of the same loci in 56 worldwide populations (available on the website
      www.allelefrequencies.net). In total, 5134 individuals were analysed and the
      populations grouped, with some exceptions, according to a geographical gradient.

PMID- 18069937
TI  - Cellular expression or binding of desLys58-beta2 microglobulin is not dependent
      on the presence of the tri-molecular MHC class I complex.
AB  - The monoclonal antibody 332-01 is a newly developed antibody which specifically
      recognizes human desLys58-beta2 microglobulin (dbeta2m). In the present study, we
      characterized the binding of 332-01 to peripheral blood mononuclear cells (PBMC),
      a number of human leukaemic and monocytic cell lines, and beta2m gene-deleted
      murine lymphocytes. dbeta2m was found to be expressed on non-activated and
      activated monocytes. When cells were pre-exposed to dbeta2m, 332-01 also bound to
      non-activated T lymphocytes. dbeta2m was expressed on the monocytic cell lines
      U937 and TIB-202, and binding was significantly increased when cells were pre
      incubated with dbeta2m and when TIB-202 cells were exposed to lipopolysaccharide.
      dbeta2m was also expressed on T leukaemic Jurkat cells as well as on low HLA
      expressing erythroleukaemic K562 cells. beta2m gene-deleted murine splenocytes
      only bound 332-01 after pre-exposure to dbeta2m. Binding of 332-01 antibody could
      not be displaced by addition of high concentrations of native beta2m. In
      conclusion, our data indicate that dbeta2m - in contrast to native beta2m - binds
      to a hitherto unknown cell surface receptor independent of classical MHC class I
      molecules. As beta2m has previously been shown to display biological activities
      such as the induction of both growth promotion and apoptosis, C1 complement
      activity, shown to mediate cleavage of beta2m, could be involved in these
      processes.

PMID- 18069939
TI  - The gibberellin biosynthetic genes AtGA20ox1 and AtGA20ox2 act, partially
      redundantly, to promote growth and development throughout the Arabidopsis life
      cycle.
AB  - The activity of the gibberellin (GA) biosynthetic enzymes GA 20-oxidases (GA20ox)
      is of particular importance in determining GA concentration in many plant
      species. In Arabidopsis these enzymes are encoded by a family of five genes:
      AtGA20ox1-AtGA20ox5. Transcript analysis indicated that they have different
      expression patterns and may thus participate differentially in GA-regulated
      developmental processes. We have used reverse genetics to determine the
      physiological roles of AtGA20ox1 and AtGA20ox2, the most highly expressed GA20ox
      genes during vegetative and early reproductive development. AtGA20ox1 and
      AtGA20ox2 act redundantly to promote hypocotyl and internode elongation,
      flowering time, elongation of anther filaments, the number of seeds that develop
      per silique and elongation of siliques, with AtGA20ox1 making the greater
      contribution to internode and filament elongation, and AtGA20ox2 making the
      greater contribution to flowering time and silique length. Pollination of the
      double mutant with wild-type pollen indicated that the GA promoting silique
      elongation is of maternal origin. The ga20ox2 phenotype revealed that GA promotes
      the number of stem internodes that elongate upon bolting, and does so
      independently of its effect on internode elongation. Comparison of the phenotype
      of the double mutant with that of the highly GA-deficient ga1-3 mutant indicates
      that other GA20ox genes contribute to all the developmental processes examined,
      and, in some cases such as root growth and leaf expansion, make major
      contributions, as these processes were unaffected in the double mutant. In
      addition, the effects of the mutations are mitigated by the homeostatic mechanism
      that acts on expression of other GA dioxygenase and GID1 receptor genes.

PMID- 18069938
TI  - The SUMO E3 ligase, AtSIZ1, regulates flowering by controlling a salicylic acid
      mediated floral promotion pathway and through affects on FLC chromatin structure.
AB  - Loss-of-function siz1 mutations caused early flowering under short days. siz1
      plants have elevated salicylic acid (SA) levels, which are restored to wild-type
      levels by expressing nahG, bacterial salicylate hydroxylase. The early flowering
      of siz1 was suppressed by expressing nahG, indicating that SIZ1 represses the
      transition to flowering mainly through suppressing SA-dependent floral promotion
      signaling under short days. Previous results have shown that exogenous SA
      treatment does not suppress late flowering of autonomous pathway mutants.
      However, the siz1 mutation accelerated flowering time of an autonomous pathway
      mutant, luminidependens, by reducing the expression of FLOWERING LOCUS C (FLC), a
      floral repressor. This result suggests that SIZ1 promotes FLC expression,
      possibly through an SA-independent pathway. Evidence indicates that SIZ1 is
      required for the full activation of FLC expression in the late-flowering FRIGIDA
      background. Interestingly, increased FLC expression and late flowering of an
      autonomous pathway mutant, flowering locus d (fld), was not suppressed by siz1,
      suggesting that SIZ1 promotes FLC expression by repressing FLD. Consistent with
      this, SIZ1 facilitates sumoylation of FLD that can be suppressed by mutations in
      three predicted sumoylation motifs in FLD (i.e. FLDK3R). Furthermore, expression
      of FLDK3R in fld protoplasts strongly reduced FLC transcription compared with
      expression of FLD, and this affect was linked to reduced acetylation of histone 4
      in FLC chromatin. Taken together, the results suggest that SIZ1 is a floral
      repressor that not only represses the SA-dependent pathway, but also promotes FLC
      expression by repressing FLD activity through sumoylation, which is required for
      full FLC expression in a FRIGIDA background.

PMID- 18069940
TI  - Induction of phenotypic variation by activation of genes harbouring a maize Spm
      element in their promoter regions using a TnpA-VP16 fusion protein.
AB  - For many crops, a narrowing genetic base is becoming an increasingly significant
      problem for improvements made through breeding. Commonly used breeding procedures
      systematically reduce genetic diversity within elite gene pools. Here we describe
      a new technique for activation of genes in lines carrying Spm or dSpm transposon
      insertions. Activation of genes in Arabidopsis harbouring Spm or dSpm insertions
      in their promoters can be induced by over-expression of the TnpA-VP16 fusion
      protein, which binds Spm ends and activates local transcription. As a result, a
      variety of phenotypes are recovered from multiple-copy Spm lines in Arabidopsis.
      Application of this technique to a number of Spm insertion collections in
      Arabidopsis provides a valuable approach for new insights into plant gene
      functions. It also provides a proof-of-principle demonstration that the method
      could be used to generate new variation in elite lines of maize.

PMID- 18069941
TI  - AtNFXL1, an Arabidopsis homologue of the human transcription factor NF-X1,
      functions as a negative regulator of the trichothecene phytotoxin-induced defense
      response.
AB  - Trichothecenes are a closely related family of phytotoxins that are produced by
      phytopathogenic fungi. In Arabidopsis, expression of AtNFXL1, a homologue of the
      putative human transcription repressor NF-X1, was significantly induced by
      application of type A trichothecenes, such as T-2 toxin. An atnfxl1 mutant
      growing on medium lacking trichothecenes showed no phenotype, whereas a
      hypersensitivity phenotype was observed in T-2 toxin-treated atnfxl1 mutant
      plants. Microarray analysis indicated that several defense-related genes (i.e.
      WRKYs, NBS-LRRs, EDS5, ICS1, etc.) were upregulated in T-2 toxin-treated atnfxl1
      mutants compared with wild-type plants. In addition, enhanced salicylic acid (SA)
      accumulation was observed in T-2 toxin-treated atnfxl1 mutants, which suggests
      that AtNFXL1 functions as a negative regulator of these defense-related genes via
      an SA-dependent signaling pathway. We also found that expression of AtNFXL1 was
      induced by SA and flg22 treatment. Moreover, the atnfxl1 mutant was less
      susceptible to a compatible phytopathogen, Pseudomonas syringae pv. tomato strain
      DC3000 (Pst DC3000). Taken together, these results indicate that AtNFXL1 plays an
      important role in the trichothecene response, as well as the general defense
      response in Arabidopsis.

PMID- 18069942
TI  - XND1, a member of the NAC domain family in Arabidopsis thaliana, negatively
      regulates lignocellulose synthesis and programmed cell death in xylem.
AB  - Members of the large Arabidopsis NAC domain transcription factor family are
      regulators of meristem development, organ elongation and separation, and
      deposition of patterned secondary cell walls. XYLEM NAC DOMAIN 1 (XND1) is highly
      expressed in xylem. Changes observed for XND1 knockout plants compared with wild
      type Arabidopsis thaliana included a reduction in both plant height and tracheary
      element length and an increase in metaxylem relative to protoxylem in roots of
      plants treated with the proteasome inhibitor MG132. Overexpression of XND1
      resulted in extreme dwarfism associated with the absence of xylem vessels and
      little or no expression of tracheary element marker genes. In contrast, phloem
      marker-gene expression was not altered and phloem-type cells still formed.
      Transmission electron microscopy showed that parenchyma-like cells in the
      incipient xylem zone in hypocotyls of XND1 overexpressors lacked secondary wall
      thickenings and retained their cytoplasmic content. Considered together, these
      findings suggest that XND1 affects tracheary element growth through regulation of
      secondary wall synthesis and programmed cell death.

PMID- 18069943
TI  - Not all ALMT1-type transporters mediate aluminum-activated organic acid
      responses: the case of ZmALMT1 - an anion-selective transporter.
AB  - The phytotoxic effects of aluminum (Al) on root systems of crop plants constitute
      a major agricultural problem in many areas of the world. Root exudation of Al
      chelating molecules such as low-molecular-weight organic acids has been shown to
      be an important mechanism of plant Al tolerance/resistance. Differences observed
      in the physiology and electrophysiology of root function for two maize genotypes
      with contrasting Al tolerance revealed an association between rates of Al
      activated root organic acid release and Al tolerance. Using these genotypes, we
      cloned ZmALMT1, a maize gene homologous to the wheat ALMT1 and Arabidopsis
      AtALMT1 genes that have recently been described as encoding functional, Al
      activated transporters that play a role in tolerance by mediating Al-activated
      organic acid exudation in roots. The ZmALMT1 cDNA encodes a 451 amino acid
      protein containing six transmembrane helices. Transient expression of a
      ZmALMT1::GFP chimera confirmed that the protein is targeted to the plant cell
      plasma membrane. We addressed whether ZmALMT1 might underlie the Al-resistance
      response (i.e. Al-activated citrate exudation) observed in the roots of the Al
      tolerant genotype. The physiological, gene expression and functional data from
      this study confirm that ZmALMT1 is a plasma membrane transporter that is capable
      of mediating elective anion efflux and influx. However, gene expression data as
      well as biophysical transport characteristics obtained from Xenopus oocytes
      expressing ZmALMT1 indicate that this transporter is implicated in the selective
      transport of anions involved in mineral nutrition and ion homeostasis processes,
      rather than mediating a specific Al-activated citrate exudation response at the
      rhizosphere of maize roots.

PMID- 18069944
TI  - Arabidopsis endo-1,4-beta-glucanases are involved in the formation of root
      syncytia induced by Heterodera schachtii.
AB  - Cyst nematodes induce root syncytia with specific features such as hypertrophy,
      increased metabolic activity and fusion with adjacent cells. Cell walls of the
      syncytia undergo massive changes such as thickening, local dissolution and
      formation of ingrowths. Cell wall degrading and modifying proteins are apparently
      involved in syncytium formation but detailed knowledge of this is still limited.
      Therefore, we studied the regulation and function of the entire Arabidopsis endo
      1,4-beta-glucanase gene family in syncytia induced by Heterodera schachtii. Endo
      1,4-beta-glucanases hydrolyze the 1,4-beta-glucosidic linkages between glucose
      residues. Using semi-quantitative and quantitative approaches we identified seven
      genes that are upregulated in syncytia. Two of these genes, coding for secreted
      AtCel2 and membrane-bound KOR3, are shoot-specific but show high expression in
      syncytia at different developmental stages. In silico analysis of the promoter
      regions of both genes compared with other genes with modified regulation in
      nematode feeding sites did not reveal specific cis-acting elements that could be
      related to specific transcription in syncytia. However, motifs responsive to
      sugar and different plant hormones were identified. Accordingly, treatments with
      sucrose, gibberellic acid and NAA induced upregulation of AtCel2, whereas ABA
      triggered downregulation of both AtCel2 and KOR3 in roots. As AtCel2 is related
      to degradation of the cell wall matrix, we analysed the hemicellulose content in
      syncytia. The measured values resembled the expression pattern of AtCel2. A
      distinctly reduced number of females developed in cel2 and kor3 T-DNA mutants,
      and we therefore conclude that endo-1,4-beta-glucanases play an important role in
      the formation and function of syncytia.

PMID- 18069945
TI  - Use of fetuin before and during vitrification of bovine oocytes.
AB  - After vitrification of oocytes, fertilization rates and subsequent development
      are unsatisfactory, possibly due in part to zona hardening. Foetal calf serum
      (FCS) can prevent zona hardening because of its fetuin content, but FCS
      composition varies among batches, and may contain viruses. In this study, we
      therefore compared media supplemented with different sources of macromolecules,
      2% bovine serum albumin (BSA), 2% BSA + 1 mg/ml fetuin and 20% FCS, for handling
      oocytes for 10-30 min prior to vitrification. None of the treatments resulted in
      developmental rates comparable with the non-vitrified controls, but FCS inclusion
      in pre-vitrification handling medium resulted in higher blastocyst production per
      oocyte (p < 0.05) (10.8%) on day 9 of culture than BSA (5.3%) or BSA + fetuin
      (6.4%). Blastocysts developing from oocytes from all vitrification treatments
      were somewhat retarded relative to those developed from non-vitrified oocytes. We
      also tested the use of fetuin during vitrification as well as two different
      exposure times with cryoprotectants, 180 and 30 s. There was no significant
      effect of fetuin or exposure time on rates of subsequent blastocyst production.

PMID- 18069946
TI  - Effect of post-IVF developmental kinetics on in vitro survival of vitrified
      warmed domestic cat blastocysts.
AB  - A limited number of reports is available on cryopreservation of in vitro
      fertilization (IVF)-derived cat blastocysts. In the present study, IVF-derived
      domestic cat embryos which reached the blastocyst stage either on day 6 or day 7
      were cryopreserved by vitrification using Cryotop as a cryodevice. Fresh control
      and post-warm surviving blastocysts were examined by differential cell staining
      with Hoechst 33342 and propidium iodide to determine total cell number and inner
      cell mass (ICM) ratio, and the post-warm survival rate was determined by re
      expansion of the blastocoel during 24 h of in vitro culture. In fresh control,
      the mean number of total cells of day 7 blastocysts (61.4 cells) tended to be
      smaller than that of day 6 blastocysts (81.9 cells, p = 0.096). The post-warm
      survival rates of day 6 and day 7 blastocysts were not statistically different
      (73.8%; 31 of 42 vs 66.7%; 18 of 27). There were no significant differences in
      the total cell number and ICM ratio between fresh control and vitrified
      blastocysts, although the ICM ratio of surviving day 7 blastocysts was
      significantly smaller than that of fresh controls (stained at day 8, 18.9% vs
      28.9%, p < 0.05). These results indicate that IVF-derived domestic cat embryos
      that reached the blastocyst stage earlier can survive the Cryotop vitrification
      without a reduction in the parameters studied.

PMID- 18069947
TI  - Study on the oestrous synchronization in gilts by using progestin altrenogest and
      hCG: its effect on the follicular development, ovulation time and subsequent
      reproductive performance.
AB  - The aim of this study was to further investigate the effect of using progestin
      altrenogest and hCG to synchronize the oestrous cycle and its effect on
      follicular development, ovulation time and subsequent reproductive performance.
      Thirty crossbred gilts were divided into three groups. Group A (control) received
      a 5 ml of normal saline for 18 consecutive days by individually top-dressing.
      Groups B and C gilts received 20 mg (5 ml) of progestin altrenogest for 18
      consecutive days by individually top-dressing. On day 3 (72 h) after withdrawal
      of progestin altrenogest, Group C gilts received hCG (500 IU, im). The follicular
      development and ovulation time were examined by transabdominal ultrasonography.
      Subsequent reproductive performances, i.e. number of total born per litter (NTB),
      number of live born per litter (NBA), number of stillbirth per litter (NSB),
      average piglet birth weight (ABW), lactation length (LL) and weaning to oestrous
      interval (WOI), were recorded. None of the gilts in Group A showed oestrus within
      10 days after withdrawal of normal saline. Groups B (eight of 10) and C gilts
      (four of 10) came into oestrus at 5.6 +/- 0.5 and 6.5 +/- 0.6 days after
      withdrawal of progestin altrenogest, respectively. The ovulation time of Groups B
      and C gilts took placed at 25.0 +/- 4.7 and 25.0 +/- 5.0 h after standing
      oestrus, respectively. The pre-ovulatory follicular size (diameter) of Groups B
      and C gilts was 8.0 +/- 2.0 and 11.0 +/- 3.0 mm, respectively. A tendency of
      larger litter size (NTB) in Group B gilts was found when compared with Group A
      gilts. To conclude, using progestin altrenogest alone can be used to synchronize
      the oestrous cycle in gilts without unenthusiastic effect on the follicular
      development, ovulation time and subsequent reproductive performances. However,
      treatment of gilts with hCG at day 3 (72 h) after withdrawal of altrenogest had
      unenthusiastic effect on oestrus synchronization.

PMID- 18069948
TI  - Effect of chemical or electrical activation of bovine oocytes on blastocyst
      development and quality.
AB  - Activation of in vitro-matured (IVM) oocytes is essential for successful embryo
      production following nuclear transfer (NT) or intracytoplasmic sperm injection
      (ICSI). This study was designed to compare the rates of blastocyst production and
      embryo quality (as measured by numbers of viable cells) following parthenogenetic
      activation with electrical pulse or the use of two different calcium ionophores,
      A23187 (CA) or ionomycin (IO), with or without the addition of bovine serum
      albumin (BSA). IVM oocytes with a first polar body were randomly allocated to
      five treatment groups: CA (5 microM CA, 5 min; n = 88), CA + BSA (5 microM CA, 5
      min; BSA, 5 min; n = 90), IO (5 microM IO, 5 min; n = 91), IO + BSA (5 microM IO,
      5 min; BSA, 5 min; n = 86) and EL (two pulses of 1.5 kV/cm, 20 micros; n = 120).
      Blastocyst rates were higher (p < 0.05) for CA (54.4%), IO (51.4%) and EL (54.5%)
      than for IO + BSA (18.3%). Treatment CA + BSA (39.8%) did not differ from the
      others. There was no difference (p > 0.05) among treatments in total number of
      cells. However, the percentage of viable cells was reduced in CA (49.9%), CA +
      BSA (45.8%), IO (64.9%), IO + BSA (50.9%) compared with EL (82.7%). In summary,
      the addition of BSA to the IO treatment had an adverse effect on blastocyst
      production rates. Although there was no difference between electrical stimulation
      and chemical activation on blastocyst production rates, electrical activation
      resulted in blastocysts with a higher percentage of viable cells.

PMID- 18069949
TI  - Ovarian responses, hormonal profiles and embryo yields in anoestrous ewes
      superovulated with Folltropin-V after pretreatment with medroxyprogesterone
      acetate-releasing vaginal sponges and a single dose of oestradiol-17beta.
AB  - In ruminants, superovulatory treatments started at the time of follicular wave
      emergence result in greater and less variable ovulatory responses and embryo
      yields compared with the treatments begun in the presence of a large growing
      antral follicle(s) from the previous waves. The progesterone-oestradiol treatment
      is routinely used for follicular wave synchronization in cattle. The main
      objective of this study was to characterize the ovarian responses, hormonal
      profiles and in vivo embryo production in anoestrous Rideau Arcott ewes (May
      June), which were superovulated after pretreatment with medroxyprogesterone
      acetate (MAP)-releasing intravaginal sponges and a single dose of oestradiol
      17beta (E(2)-17beta). Six days after insertion of MAP sponges, eight ewes were
      given an i.m. injection of 350 microg of E(2)-17beta (E(2)-17beta-treated ewes);
      10 ewes were given an i.m. injection of vehicle (control ewes). Multiple-dose
      Folltropin-V treatment, followed by the bolus injection of GnRH (50 microg i.m.),
      began 6 days after E(2)-17beta/vehicle injection. Transrectal ovarian
      ultrasonography revealed that: (i) the interval between E(2)-17beta/vehicle
      injection and regression of all follicles > or =5 to 3 mm in diameter was shorter
      (p < 0.01; 2.6 +/- 0.4 vs 4.8 +/- 0.6 days respectively); and (ii) the interval
      between injection and emergence of the next follicular wave was longer (p < 0.05;
      5.4 +/- 0.3 vs 1.2 +/- 0.4 days, respectively) in E(2)-17beta-treated than in
      control ewes. During the 6 days after injection, the mean FSH peak concentration
      and basal FSH concentration were lower (p < 0.01) in E(2)-17beta-treated ewes.
      The mean ovulation rate and the number of recovered embryos did not differ (p >
      0.05) between the two groups of ewes. However, the number of luteinized
      unovulated follicles per ewe, and the variability in the number of luteal
      structures and overall embryo yield were less (p < 0.05) in E(2)-17beta-treated
      compared with control ewes. In conclusion, the MAP-E(2)-17beta pretreatment
      significantly reduced the variability in ovarian responses and embryo yields,
      without affecting the embryo production in superovulated anoestrous ewes.

PMID- 18069950
TI  - Plant peptides and peptidomics.
AB  - Extracellular plant peptides perform a large variety of functions, including
      signalling and defence. Intracellular peptides often have physiological functions
      or may merely be the products of general proteolysis. Plant peptides have been
      identified and, in part, functionally characterized through biochemical and
      genetic studies, which are lengthy and in some cases impractical. Peptidomics is
      a branch of proteomics that has been developed over the last 5 years, and has
      been used mainly to study neuropeptides in animals and the degradome of
      proteases. Peptidomics is a fast, efficient methodology that can detect minute
      and transient amounts of peptides and identify their post-translational
      modifications. This review describes known plant peptides and introduces the use
      of peptidomics for the detection of novel plant peptides.

PMID- 18069951
TI  - Distribution of interstitial cells of Cajal and nitrergic neurons in normal and
      diabetic human appendix.
AB  - The objective of this study was to determine the distribution of enteric nerves
      and interstitial cells of Cajal (ICC) in the normal human appendix and in type 1
      diabetes. Appendixes were collected from patients with type 1 diabetes and from
      non-diabetic controls. Volumes of nerves and ICC were determined using 3-D
      reconstruction and neuronal nitric oxide synthase (nNOS) expressing neurons were
      counted. Enteric ganglia were found in the myenteric plexus region and within the
      longitudinal muscle. ICC were found throughout the muscle layers. In diabetes, c
      Kit positive ICC volumes were significantly reduced as were nNOS expressing
      neurons. In conclusion, we describe the distribution of ICC and enteric nerves in
      health and in diabetes. The data also suggest that the human appendix, a readily
      available source of human tissue, may be useful model for the study of motility
      disorders.

PMID- 18069952
TI  - Isolate specificity of quantitative trait loci for partial resistance of barley
      to Puccinia hordei confirmed in mapping populations and near-isogenic lines.
AB  - Partial resistance is considered race-nonspecific and durable, consistent with
      the concept of 'horizontal' resistance. However, detailed observations of partial
      resistance to leaf rust (Puccinia hordei) in barley (Hordeum vulgare) revealed
      small cultivar x isolate interactions, suggesting a minor-gene-for-minor-gene
      interaction model, similar to so-called 'vertical' resistance. Three consistent
      quantitative trait loci (QTLs), labelled Rphq2, Rphq3 and Rphq4, that were
      detected in the cross susceptible L94 x partially resistant Vada have been
      incorporated into the L94 background to obtain near-isogenic lines (NILs). Three
      isolates were used to map QTLs on seedlings of the L94 x Vada population and to
      evaluate the effect of each QTL on adult plants of the respective NILs under
      field conditions. Rphq2 had a strong effect in seedlings but almost no effect in
      adult plants, while Rphq3 was effective in seedlings and in adult plants against
      all three isolates. However, Rphq4 was effective in seedlings and in adult plants
      against two isolates but ineffective in both development stages against the
      third, demonstrating a clear and reproducible isolate-specific effect. The
      resistance governed by the three QTLs was not associated with a hypersensitive
      reaction. Those results confirm the minor-gene-for-minor-gene model suggesting
      specific interactions between QTLs for partial resistance and P. hordei isolates.

PMID- 18069953
TI  - Quantifying foliar uptake of gaseous nitrogen dioxide using enriched foliar
      delta15N values.
AB  - The magnitude and impact of gaseous nitrogen dioxide (NO(2)) directly entering
      the leaves were investigated using foliar nitrogen isotopic composition
      (delta(15)N) values in tomato (Lycopersicon esculentum) and tobacco (Nicotiana
      tabacum). Using a hydroponics-fumigation system, (15)NO(2) (20 and 40 ppb) was
      supplied to shoot systems and (50 and 500 microM) was supplied to root systems.
      Morphological, stable isotope and nitrate reductase activity (NRA) analyses were
      used to quantify foliar NO(2) uptake and to examine whether realistic
      concentrations of NO(2) influenced plant metabolism. Nicotiana tabacum and L.
      esculentum incorporated 15 and 11%, respectively, of (15)NO(2)-N into total
      biomass via foliar uptake under low supply. On a mass basis, N. tabacum and L.
      esculentum incorporated 3.3 +/- 0.9 and 3.1 +/- 0.8 mg of (15)NO(2)-N into
      biomass, respectively, regardless of availability. There were no strong effects
      on biomass accumulation or allocation, leaf delta(13)C values, or leaf or root
      NRA in response to NO(2) exposure. Foliar NO(2 )uptake may contribute a
      significant proportion of N to plant metabolism under N-limited conditions, does
      not strongly influence growth at 40 ppb, and may be traced using foliar
      delta(15)N values.

PMID- 18069954
TI  - Recurrent soil freeze-thaw cycles enhance grassland productivity.
AB  - Ongoing global warming will increase the frequency of soil freeze-thaw cycles
      (FTCs) in cool-temperate and other high-latitude regions. The spatial relevance
      of seasonally frozen ground amounts to c. 55% of the total land area of the
      northern hemisphere. Evidence suggests that FTCs contribute to nutrient dynamics.
      Knowledge of their effects on plant communities is scarce, although plants may be
      the decisive factor in controlling ecosystem functions such as nutrient
      retention. Here, the effects are analysed of five additional FTCs in winter for
      the above- and below-ground productivity of experimental grassland communities
      and soil enzymatic activity over the following growing season. Freeze-thaw cycles
      increased the above-ground productivity but reduced root length over the whole
      subsequent growing season. In summer, no changes in soil enzymatic activities
      representing the carbon, nitrogen and phosphorus cycles were observed in the FTC
      manipulated plots, except for an increased cellobiohydrolase activity. Changes in
      productivity resulting in an increased shoot-to-root ratio and shifts in timing
      are capable of altering ecosystem stability and ecosystem services, such as
      productivity and nutrient retention.

PMID- 18069955
TI  - Systemic induction of phloem secondary metabolism and its relationship to
      resistance to a canker pathogen in Austrian pine.
AB  - The mechanisms and conditions affecting expression of systemic induced resistance
      (SIR) in pine are not clearly understood. Two hypotheses were tested here: that
      SIR against a pathogen induced by either a pathogen or an insect involves
      coordinated shifts in phloem secondary metabolism; and that fertility affects the
      production of these compounds. To test these hypotheses, a tripartite system was
      used comprising Austrian pine (Pinus nigra) grown under three different fertility
      regimes, the fungal pathogen Diplodia pinea, and the defoliator Neodiprion
      sertifer. Fungal induction led to systemic accumulation of lignin, phenolic
      glycosides and stilbenes, whereas insect defoliation led to an increase in
      germacrene D concentration in branch phloem. Fertility affected the
      concentrations of only the phenolic glycosides. Multivariate analyses showed
      coregulation of compounds within at least three consistent groupings: phenolic
      glycosides, stilbenes and monoterpenes. As groups and as individual compounds,
      accumulation of phenolic glycosides and stilbenes was negatively correlated with
      disease susceptibility. The experimental manipulation of the phenolics and
      terpenoids metabolic networks achieved in this study by biotic induction and
      changes in nutrient availability suggests that lignin, phenolic glycosides and
      stilbenes are important biochemical factors in the expression of SIR against the
      pathogen in this system.

PMID- 18069956
TI  - Organic acid accumulation may inhibit N2 fixation in phosphorus-stressed lupin
      nodules.
AB  - Nodulated lupins (Lupinus angustifolius cv. Wonga) were hydroponically grown
      under conditions of low phosphate (LP) or adequate phosphate (HP) to assess the
      effect of phosphoenolpyruvate carboxylase (PEPC)-derived organic acids on
      nitrogen assimilation in LP nodules. LP conditions are linked to altered organic
      acid metabolism, by the engagement of PEP metabolism via PEPC. In LP nodules, the
      enhanced organic acid synthesis may reduce the available organic carbon for
      nitrogen assimilation. The diversion of carbon between the organic acid- and
      amino acid pools was assessed through key nodular enzymes and (14)CO(2)
      metabolism. Under LP conditions, increased rates of organic acid synthesis via
      PEPC and malate dehydrogenase (MDH), coincided with reduced nitrogen assimilation
      via aspartate aminotransferase (AAT), aspartate synthetase (AS) and glutamine
      synthetase (GS)/glutamate synthase (GOGAT) activities. There was a preferential
      metabolism of nodular (14)CO(2) into organic acids and particularly into malate.
      High malate levels were associated with reduced N(2) fixation and synthesis of
      amino acids. These results indicate that phosphorus deficiency can enhance malate
      synthesis in nodules, but that excessive malate accumulation may inhibit N(2)
      fixation and nitrogen assimilation.

PMID- 18069957
TI  - New tools for labeling silica in living diatoms.
AB  - Silicon biomineralization is a widespread mechanism found in several kingdoms
      that concerns both unicellular and multicellular organisms. As a result of
      genomic and molecular tools, diatoms have emerged as a good model for
      biomineralization studies and have provided most of the current knowledge on this
      process. However, the number of techniques available to study its dynamics at the
      cellular level is still rather limited. Here, new probes were developed
      specifically to label the pre-existing or the newly synthesized silica frustule
      of several diatoms species. It is shown that the LysoTracker Yellow HCK-123,
      which can be used to visualize silica frustules with common filter sets, presents
      an enhanced signal-to-noise ratio and allows details of the frustules to be
      imaged without of the use of ionophores. It is also demonstrated that
      methoxysilane derivatives can be coupled to fluorescein-5-isothiocyanate (FITC)
      to preferentially label the silica components of living cells. The coupling of
      labeling procedures might help to address the challenging question of the process
      of frustule exocytosis.

PMID- 18069958
TI  - Water-use efficiency of forest ecosystems in eastern China and its relations to
      climatic variables.
AB  - Carbon (C) and water cycles of terrestrial ecosystems are two coupled ecological
      processes controlled partly by stomatal behavior. Water-use efficiency (WUE)
      reflects the coupling relationship to some extent. At stand and ecosystem levels,
      the variability of WUE results from the trade-off between water loss and C gain
      in the process of plant photosynthetic C assimilation. Continuous observations of
      C, water, and energy fluxes were made at three selected forest sites of ChinaFLUX
      with eddy covariance systems from 2003 to 2005. WUE at different temporal scales
      were defined and calculated with different C and water flux components.
      Variations in WUE were found among three sites. Average annual WUE was 9.43 mg
      CO(2) g(-1) H(2)O at Changbaishan temperate broad-leaved Korean pine mixed
      forest, 9.27 mg CO(2) g(-1) H(2)O at Qianyanzhou subtropical coniferous
      plantation, and 6.90 mg CO(2) g(-1) H(2)O at Dinghushan subtropical evergreen
      broad-leaved forest. It was also found that temperate and subtropical forest
      ecosystems had different relationships between gross primary productivity (GPP)
      and evapotranspiration (ET). Variations in WUE indicated the difference in the
      coupling between C and water cycles. The asynchronous response of GPP and ET to
      climatic variables determined the coupling and decoupling between C and water
      cycles for the two regional forest ecosystems.

PMID- 18069959
TI  - Novel way of measuring the fracture toughness of leaves and other thin films
      using a single inclined razor blade.
AB  - A new test for measuring leaf fracture toughness by cutting with a single
      inclined razor blade is described here, this having been developed to overcome
      some of the inadequacies of conventional double-bladed cutting tests, such as
      scissoring and shearing. The accuracy and precision of this test were determined
      by measuring the fracture toughness of various leaf types and homogeneous films,
      and comparing the results with those obtained by scissoring. The new test was
      found to display a low friction of cutting with great precision in measurements.
      Fracture toughness measurements of the specimens were considerably lower for the
      new test than those obtained by scissoring, owing to greater blade sharpness and
      reduced damage to the specimens during cutting. Despite this, the rankings of
      fracture toughness measurements for the specimens are similar for both the new
      test and scissoring, thus demonstrating the test's consistency with scissoring.
      The new test was found to be successful in measuring the fracture toughness of
      leaf blades and other thin, film-like materials. It was also able to overcome
      some of the difficulties of conventional double-bladed cutting tests, especially
      the estimation of energy expenditure that is extraneous to the work of cutting.

PMID- 18069960
TI  - Spatio-temporal quantification of differential growth processes in root growth
      zones based on a novel combination of image sequence processing and refined
      concepts describing curvature production.
AB  - Differential growth processes in root and shoot growth zones are governed by the
      transport kinetics of auxin and other plant hormones. While gene expression and
      protein localization of hormone transport facilitators are currently being
      unraveled using state-of-the-art techniques of live cell imaging, the
      quantitative analysis of growth reactions is lagging behind because of a lack of
      suitable methods. A noninvasive technique, based on digital image sequence
      processing, for visualizing and quantifying highly resolved spatio-temporal root
      growth processes was applied in the model plant Arabidopsis thaliana and was
      adapted to provide precise information on differential curvature production
      activity within the root growth zone. Comparison of root gravitropic curvature
      kinetics in wild-type and mutant plants altered in a facilitator for auxin
      translocation allowed the determination of differences in the location and in the
      temporal response of curvature along the growth zone between the investigated
      plant lines. The findings of the quantitative growth analysis performed here
      confirm the proposed action of the investigated transport facilitator. The
      procedure developed here for the investigation of differential growth processes
      is a valuable tool for characterizing the phenomenology of a wide range of shoot
      and root growth movements and hence facilitates elucidation of their molecular
      characterization.

PMID- 18069961
TI  - Susceptibility to Phytophthora ramorum in a key infectious host: landscape
      variation in host genotype, host phenotype, and environmental factors.
AB  - Sudden oak death is an emerging forest disease caused by the invasive pathogen
      Phytophthora ramorum. Genetic and environmental factors affecting susceptibility
      to P. ramorum in the key inoculum-producing host tree Umbellularia californica
      (bay laurel) were examined across a heterogeneous landscape in California, USA.
      Laboratory susceptibility trials were conducted on detached leaves and assessed
      field disease levels for 97 host trees from 12 225-m(2) plots. Genotype and
      phenotype characteristics were assessed for each tree. Effects of plot-level
      environmental conditions (understory microclimate, amount of solar radiation and
      topographic moisture potential) on disease expression were also evaluated.
      Susceptibility varied significantly among U. californica trees, with a fivefold
      difference in leaf lesion size. Lesion size was positively related to leaf area,
      but not to other phenotypic traits or to field disease level. Genetic diversity
      was structured at three spatial scales, but primarily among individuals within
      plots. Lesion size was significantly related to amplified fragment length
      polymorphism (AFLP) markers, but local environment explained most variation in
      field disease level. Thus, substantial genetic variation in susceptibility to P.
      ramorum occurs in its principal foliar host U. californica, but local environment
      mediates expression of susceptibility in nature.

PMID- 18069962
TI  - Height convergence in response to neighbour growth: genotypic differences in the
      stoloniferous plant Potentilla reptans.
AB  - Using a new experimental set up, the way in which height growth of stoloniferous
      plants is adjusted to that of their neighbours, as well as differences between
      genotypes in their ability to keep up with neighbour height growth were tested.
      Five Potentilla reptans genotypes inherently differing in petiole length were
      subjected to three experimental light gradients, involving light intensity and
      red : far-red ratio. Each plant was placed in a vertically adjustable cylinder of
      green foil, and the treatments differed in the speed of cylinder height increase
      and final height. Total weight of plants decreased from the 'Slow' to the 'Fast'
      treatment, while petiole length increased. Leaves reaching the top of the
      cylinder stopped petiole elongation, resulting in similar final heights for all
      genotypes in the 'Slow' treatment. In the 'Fast' treatment only the fastest
      growing genotype maintained its position in the top of the cylinder and genotypes
      differed strongly in final height within the cylinders. Plants adjust their
      height growth to that of the surrounding vegetation, leading to height
      convergence in short light gradients that slowly increase. These adjustments and
      genotypic differences in ability to keep up with fast-growing neighbours can
      influence the outcome of competition for light.

PMID- 18069964
TI  - Tapering of xylem conduits and hydraulic limitations in sycamore (Acer
      pseudoplatanus) trees.
AB  - Vertical conduit tapering is proposed as an effective mechanism to almost
      eliminate the increase in hydraulic resistance with increased height. Despite
      this potential role, very little is known about its changes during ontogeny.
      Here, conduit tapering and stem morphology of young/small and old/tall
      individuals of Acer pseudoplatanus in the field, as well as 3-yr-old grafted
      trees from both age classes, were analysed. The distribution of hydraulic
      resistance along stems was also determined in a subsample of trees. Substantial
      conduit tapering was found in small trees (field-grown and grafted from both age
      classes), whereas values were lower in tall trees, indicating that tapering was a
      size-related, not an age-related process. Apical conduit diameters were larger in
      tall trees and were inversely correlated with the degree of tapering. Hydraulic
      resistance increased less than linearly with distance from the apex. Its scaling
      against distance was indistinguishable from that predicted from anatomical
      measurements. Conduit tapering was an effective but partial mechanism of
      compensation for the increase in hydraulic resistance with tree height. Size
      related changes in tapering and in apical conduit diameters may be explained by
      the combined need to reduce the build-up of hydraulic resistance while minimizing
      the carbon costs of building vessel walls.

PMID- 18069963
TI  - Two independent estimations of stand-level root respiration on clonal Eucalyptus
      stands in Congo: up scaling of direct measurements on roots versus the trenched
      plot technique.
AB  - Root respiration at the level of a forest stand, an important component of
      ecosystem carbon balance, has been estimated in the past using various methods,
      most of them being indirect and relying on soil respiration measurements. On a 3
      yr-old Eucalyptus stand in Congo-Brazzaville, a method involving the upscaling of
      direct measurements made on roots in situ, was compared with an independent
      approach using soil respiration measurements conducted on control and trenched
      plots (i.e. without living roots). The first estimation was based on the
      knowledge of root-diameter distribution and on a relationship between root
      diameter and specific respiration rates. The direct technique involving the
      upscaling of direct measurements on roots resulted in an estimation of 1.53
      micromol m(-2) s(-1), c. 50% higher than the mean estimation obtained with the
      indirect technique (1.05 micromol m(-2) s(-1)). Monte-Carlo simulations showed
      that the results carried high uncertainty, but this uncertainty was no higher for
      the direct method than for the trenched-plot method. The reduction of the
      uncertainties on upscaled results requires more extensive knowledge of
      temperature sensitivity and more confidence and precision on the respiration
      rates and biomasses of fine roots.

PMID- 18069965
TI  - Activation of the Cpx regulon destabilizes the F plasmid transfer activator,
      TraJ, via the HslVU protease in Escherichia coli.
AB  - The Escherichia coli CpxAR two-component signal transduction system senses and
      responds to extracytoplasmic stress. The cpxA101* allele was previously found to
      reduce F plasmid conjugation by post-transcriptional inactivation of the positive
      activator TraJ. Microarray analysis revealed upregulation of the protease
      chaperone pair, HslVU, which was shown to degrade TraJ in an E. coli C600
      cpxA101* background. Double mutants of cpxA101* and hslV or hslU restored TraJ
      and F conjugation to wild-type levels. The constitutive overexpression of nlpE,
      an outer membrane lipoprotein that induces the Cpx stress response, also led to
      HslVU-mediated degradation of TraJ and repression of F transfer. However, Cpx
      mediated TraJ degradation appears to be growth phase-dependent, as induction of
      nlpE in mid-log phase cells did not appreciably alter TraJ levels. Further, His6
      TraJ was sensitive to HslVU degradation in vitro only when it was purified from
      cells overexpressing nlpE. Thus, TraJ appears to become resistant to HslVU during
      normal growth, with this resistance mapping to the F transfer region.
      Extracytoplasmic stress prevents this modification of TraJ, leaving it
      susceptible to HslVU. Thus, the CpxAR stress response indirectly controls the
      synthesis of the F mating apparatus, a complex transenvelope type IV secretion
      system, by degrading TraJ.

PMID- 18069966
TI  - Acquisition of a bacterial RumA-type tRNA(uracil-54, C5)-methyltransferase by
      Archaea through an ancient horizontal gene transfer.
AB  - The Pyrococcus abyssi genome displays two genes possibly coding for S-adenosyl-l
      methionine-dependent RNA(uracil, C5)-methyltransferases (PAB0719 and PAB0760).
      Their amino acid sequences are more closely related to Escherichia coli RumA
      catalysing the formation of 5-methyluridine (m(5)U)-1939 in 23S rRNA than to E.
      coli TrmA (tRNA methyltransferase A) methylating uridine-54 in tRNA. Comparative
      genomic and phylogenetic analyses show that homologues of PAB0719 and PAB0760
      occur only in a few Archaea, these genes having been acquired via a single
      horizontal gene transfer from a bacterial donor to the common ancestor of
      Thermococcales and Nanoarchaea. This transfer event was followed by a duplication
      event in Thermococcales leading to two closely related genes. None of the gene
      products of the two P. abyssi paralogues catalyses in vitro the formation of
      m(5)U in a P. abyssi rRNA fragment homologous to the bacterial RumA substrate.
      Instead, PAB0719 enzyme (renamed (Pab)TrmU54) displays an identical specificity
      to TrmA, as it catalyses the in vitro formation of m(5)U-54 in tRNA. Thus, during
      evolution, at least one of the two P. abyssi RumA-type enzymes has changed of
      target specificity. This functional shift probably occurred in an ancestor of all
      Thermococcales. This study also provides new evidence in favour of a close
      relationship between Thermococcales and Nanoarchaea.

PMID- 18069967
TI  - Gastric emptying and the organization of antro-duodenal pressures in the
      critically ill.
AB  - The motor dysfunctions underlying delayed gastric emptying (GE) in critical
      illness are poorly defined. Our aim was to characterize the relationship between
      antro-duodenal (AD) motility and GE in critically ill patients. AD pressures were
      recorded in 15 mechanically ventilated patients and 10 healthy volunteers for 2 h
      (i) during fasting, (ii) following an intragastric nutrient bolus with concurrent
      assessment of GE using the (13)C-octanoate breath test and (iii) during duodenal
      nutrient infusion. Propagated waves were characterized by length and direction of
      migration. Critical illness was associated with: (i) slower GE (GEC: 3.47 +/- 0.1
      vs 2.99 +/- 0.2; P = 0.046), (ii) fewer antegrade (duodenal: 44%vs 83%, AD: 16%vs
      83%; P < 0.001) and more retrograde (duodenal: 46%vs 12%, AD: 38%vs 4%; P <
      0.001) waves, (iii) shorter wave propagation (duodenal: 4.7 +/- 0.3 vs 6.0 +/-
      0.4 cm; AD: 7.7 +/- 0.6 vs 10.9 +/- 0.9 cm; P = 0.004) and (iv) a close
      correlation between GE with the percentage of propagated phase 3 waves that were
      antegrade (r = 0.914, P = 0.03) and retrograde (r = -0.95, P = 0.014). In
      critical illness, the organization of AD pressure waves is abnormal and
      associated with slow GE.

PMID- 18069968
TI  - Bunina bodies in amyotrophic lateral sclerosis.
AB  - Bunina bodies, which are small eosinophilic intraneuronal inclusions in the
      remaining lower motor neurons, are generally considered to be a specific
      pathologic hallmark of amyotrophic lateral sclerosis (ALS). One year before a
      publication by Bunina, van Reeth et al. described similar intracytoplasmic
      inclusions in the anterior horn cells in a patient with Pick's dementia with
      atypical ALS. At present, only two proteins have been shown to be present in
      Bunina bodies, one is cystatin C and the other is transferrin. Bunina bodies
      consist of amorphous electron-dense material surrounded by tubular and vesicular
      structures on electron microscopy. Although the nature and significance of Bunina
      bodies in ALS are not yet clear, the bodies may be abnormal accumulations of
      unknown proteinous materials.

PMID- 18069969
TI  - Changes in density of calcium-binding-protein-immunoreactive GABAergic neurons in
      prefrontal cortex in schizophrenia and bipolar disorder.
AB  - There is evidence that GABAergic neurotransmission is altered in mental disorders
      such as schizophrenia (SCZ) and bipolar disorder (BPD). The calcium-binding
      proteins (CBPs) calbindin (CB), calretinin (CR), and parvalbumin (PV) are used as
      markers of specific subpopulations of cortical GABAergic interneurons. We
      examined the postmortem prefrontal cortical region (Brodmann's area 9) of
      patients with SCZ and BPD, and of age-matched control subjects, excluding suicide
      cases. The laminar density of neurons immunoreactive (IR) for three CBPs, namely
      CB, CR, and PV, was quantified. The densities of CB-IR neurons in layer 2 and PV
      IR neurons in layer 4 in the SCZ subjects decreased compared with those in the
      control subjects. When CBP-IR neurons were classified according to their size, a
      reduction in the density of medium CB-IR neurons in layer 2 in SCZ subjects and
      an increase in the density of large CR-IR neurons in layer 2 in BPD subjects were
      observed. These results suggest that alterations in specific GABAergic neurons
      are present in mental disorders, and that such alterations may reflect the
      vulnerability toward the disorders.

PMID- 18069970
TI  - Stem cell-based cell therapy for Huntington disease: a review.
AB  - Huntington disease (HD) is a devastating neurodegenerative disorder and no proven
      medical therapy is currently available to mitigate its clinical manifestations.
      Although fetal neural transplantation has been tried in both preclinical and
      clinical investigations, the efficacy is not satisfactory. With the recent
      explosive progress of stem cell biology, application of stem cell-based therapy
      in HD is an exciting prospect. Three kinds of stem cells, embryonic stem cells,
      bone marrow mesenchymal stem cells and neural stem cells, have previously been
      utilized in cell therapy in animal models of neurological disorders. However,
      neural stem cells were preferably used by investigators in experimental HD
      studies, since they have a clear capacity to become neurons or glial cells after
      intracerebral or intravenous transplantation, and they induce functional
      recovery. In this review, we summarize the current state of cell therapy
      utilizing stem cells in experimental HD animal models, and discuss the future
      considerations for developing new therapeutic strategies using neural stem cells.

PMID- 18069971
TI  - Differential activation of mononuclear phagocytes in cerebellar malformation
      associated with Walker-Warburg syndrome.
AB  - Walker-Warburg syndrome (WWS) is an autosomal recessive disorder with alterations
      affecting the CNS that are characteristic of type-II lissencephaly and
      dysplasia/hypoplasia of the cerebellum. Other than these features, WWS is
      typically also accompanied by muscular dystrophy and abnormalities affecting the
      eyes. There is at present little information on the state of microglial and
      mononuclear phagocytic cell responses within the brain in WWS. In this case
      report, we present evidence for focal and differential activation of mononuclear
      phagocytes specifically confined to the dysplastic cerebellum of an infant at 5
      months of age, diagnosed with WWS.

PMID- 18069972
TI  - Papillary tumor of the pineal region.
AB  - Primary pineal gland malignancies are uncommon and seldom have papillary
      architecture. We report a case of a 22-year-old male patient who presented with
      progressive headache, horizontal nystagmus and worsening diplopia. MRI of the
      brain showed a lesion in the pineal region. The patient was taken for resection
      of the lesion which was classified as papillary tumor of pineal region (PTPR).
      Histologically, the neoplasm was cellular, characterized by eosinophilic cells
      with indistinct borders, large pleomorphic nuclei, numerous apoptotic figures
      without necrosis or microvascular proliferation. Prominent perivascular
      pseudorosettes were seen. Diffuse immunoreactivity for cytokeratin 8-18 was
      noted. Synaptophysin antibody showed membranous and cytoplasmic positivity. Weak
      staining for GFAP, vimentin, S-100 protein, and neuron specific enolase (NSE)
      were observed only focally. This is a case report of this rare pineal region
      neoplasm which only recently has been described as a histopathologic entity.
      Although the clinicopathological characteristics of this tumor are not entirely
      understood, a brief review of the literature as well as our contribution suggest
      an indolent neoplasm with a tendency for local recurrence. Histologically, PTPR
      demonstrates a unique assortment of epithelial, ependymal, and neuroendocrine
      features. The differential diagnosis of papillary neoplasms of the pineal region
      is reviewed.

PMID- 18069973
TI  - Evaluation of hepatotropic targeting properties of allogenic and xenogenic
      erythrocyte ghosts in normal and liver-injured rats.
AB  - BACKGROUND/AIMS: Haemoglobin-depleted erythrocyte ghosts have been recommended as
      vesicle carriers of drugs with hepatotropic properties. However, the influence of
      liver injury on ghost elimination and targeting has not been reported so far.
      METHODS: Human and rat ghosts were prepared and loaded with model substances, and
      the basic parameters were characterized. Ghosts were injected intravenously into
      rats with acute, subacute and chronic liver injuries. Elimination from
      circulation, organ distribution and cellular targeting was measured. The uptake
      of ghosts by liver macrophages/Kupffer cells was determined in cell culture.
      RESULTS: Ghosts are strong hepatotropic carriers with a recovery of 90% in normal
      liver. Kupffer cells are the almost exclusive target cell type. Hepatotropic
      properties remain in rats with chronic liver diseases, but are reduced by 60-70%
      in acute liver damage as a result of decline of phagocytosis of
      macrophages/Kupffer cells. Although the uptake of ghosts per gram liver tissue in
      chronic liver injury was also reduced by about 40%, the increase of liver mass
      and of macrophages/Kupffer cells compensated for the reduced phagocytotic
      activity. In subacute injury, the uptake per gram liver tissue was only
      moderately reduced. CONCLUSION: Drug targeting with ghosts might be feasible in
      chronic and subacute liver injuries, e.g. fibrogenesis and tumours, because the
      content of ingested ghosts is released by Kupffer cells into the micro
      environment, providing the uptake by and pharmacological effects on adjacent
      cells.

PMID- 18069974
TI  - Molecular pathogenesis of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third
      leading cause of cancer death worldwide. Hepatocarcinogenesis is a multistep
      process evolving from normal through chronic hepatitis/cirrhosis and dysplastic
      nodules to HCC. With advances in molecular methods, there is a growing
      understanding of the molecular mechanisms in hepatocarcinogenesis.
      Hepatocarcinogenesis is strongly linked to increases in allelic losses,
      chromosomal changes, gene mutations, epigenetic alterations and alterations in
      molecular cellular pathways. Some of these alterations are accompanied by a
      stepwise increase in the different pathological disease stages in
      hepatocarcinogenesis. Overall, a detailed understanding of the underlying
      molecular mechanisms involved in the progression of HCC is of fundamental
      importance to the development of effective prevention and treatment regimes for
      HCC.

PMID- 18069975
TI  - Gallstones are associated with carotid atherosclerosis.
AB  - BACKGROUND/AIMS: Gallstone disease (GD) and cardiovascular disease (CD) are
      common diseases worldwide with considerable economical impact and they are
      strongly associated. Carotid atherosclerosis is an excellent marker of risk for
      CD like stroke and myocardial infarction. The aim of this study was to assess the
      association between gallstones and carotid atherosclerosis. METHODS: A cross
      sectional study was conducted. We evaluated subjects with ultrasonographical
      evidence of GD and asymptomatic subjects without such evidence. Anthropometric,
      clinical and biochemical variables were collected. The Metabolic syndrome was
      evaluated using adult treatment panel III criteria. Carotid artery intima-media
      thickness (CIMT) was determined by a standard ultrasound protocol. Insulin-like
      growth factor-1 (IGF-1) serum levels were measured in all subjects. RESULTS: We
      studied 191 subjects: 62 subjects with GD (53.2% males) and 129 asymptomatic
      subjects without GD (65.9% males). Subjects with GD exhibited a higher body mass
      index, body fat percent, insulin serum levels and CIMT (P<0.05 for all). The
      prevalence of GD was higher in subjects with a CIMT>0.75 independently of other
      factors [odds ratio (OR) 2.12, 95% confidence interval (CI) 1.04-4.34; P=0.039],
      and for every 0.1 mm increase in CIMT the independent probability to be a case of
      GD increased by a factor of 1.25 (95% CI 1.02-1.53; P=0.027). IGF-1 levels did
      not differ among groups. CONCLUSIONS: Subjects with GD exhibit greater carotid
      atherosclerosis, and therefore have a higher risk for stroke and myocardial
      infarction.

PMID- 18069976
TI  - Microbial-mediated release of bisphenol A from polycarbonate vessels.
AB  - AIM: To identify the source of bisphenol A (BPA) [2,2'-bis(4-hydroxyphenyl)
      propane] in cultures of an antibiotic-producing Bacillus sp. strain grown in
      polycarbonate flasks. METHODS AND RESULTS: Although a culture of an antibiotic
      producing Bacillus sp. strain grown in a new, rinsed polycarbonate flask yielded
      BPA, duplicate cultures grown in thoroughly washed polycarbonate flasks did not.
      Cells of Escherichia coli strain C were grown in new polycarbonate flasks rinsed
      three-times with 100 ml distilled H2O. BPA was only recovered from cultures grown
      in new polycarbonate flasks, but not from the autoclaved medium incubated in
      parallel. CONCLUSIONS: BPA was present in either Bacillus or E. coli cultures,
      probably due to its release from inadequately washed polycarbonate flasks.
      Standard autoclaving did not result in BPA appearance; microbial growth was
      required. Polycarbonate vessels for microbial cultures should be thoroughly
      washed to avoid the appearance of BPA in culture medium. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This study rigorously demonstrates that the presence of BPA in
      culture medium was a consequence of microbial growth or metabolism in
      inadequately washed polycarbonate flasks. As BPA exhibits antimicrobial and
      oestrogenic activity, searches for novel drugs or production of recombinant
      chemotherapeutic agents could be derailed by the artefactual appearance of BPA.

PMID- 18069977
TI  - Re: Isolation of Escherichia Coli O157:H7 strains that do not produce Shiga toxin
      from bovine, avian and environmental sources.

PMID- 18069978
TI  - A new colorimetric microtitre model for the detection of Staphylococcus aureus
      biofilms.
AB  - AIMS: Research on biofilms requires validated quantitative models that focus both
      on matrix and viable bacterial mass. In this study, a new microplate model for
      the detection of Staphylococcus aureus biofilms was developed. METHODS AND
      RESULTS: Dimethyl methylene blue (DMMB) dye was used to quantify biofilm matrix
      colorimetrically. Initially developed for the detection of glycosaminoglycans,
      the DMMB protocol was optimized for S. aureus biofilm research. In addition, the
      redox indicator resazurin was used to determine the viable bacterial biofilm
      burden. CONCLUSION: A new, simple and reproducible microplate test system based
      on DMMB and resazurin, offering a reliable differentiation between biofilm matrix
      and cellular activity, was developed and validated for the detection of S. aureus
      biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: The DMMB-resazurin microtitre
      plate model is a valuable tool for high capacity screening of biocides and for
      the development of synergistic mixtures of biocides, destroying both biofilm
      matrix and bacteria.

PMID- 18069979
TI  - The polyphenol (-)-epicatechin gallate disrupts the secretion of virulence
      related proteins by Staphylococcus aureus.
AB  - AIM: (-)-epicatechin gallate (ECg) modifies the morphology, cell wall
      architecture and beta-lactam antibiotic susceptibility of Staphylococcus aureus.
      As these effects result primarily from intercalation into the bacterial
      cytoplasmic membrane, the capacity of ECg to modulate the secretion of two key
      staphylococcal virulence factors, coagulase and alpha-toxin, was examined.
      METHODS AND RESULTS: Bioassays were used to determine coagulase and haemolysin
      activity in culture supernatants of a number of S. aureus isolates grown in the
      presence and absence of ECg; alpha-toxin secretion was also evaluated by
      immunoblotting. Growth in ECg reduced the levels of activity of both proteins in
      culture supernatants; the effects could only be partly explained by ECg-mediated
      inhibition of bioactivity and by induction of secreted proteases. CONCLUSION: ECg
      suppresses the secretion of coagulase and alpha-toxin by clinical isolates of S.
      aureus. SIGNIFICANCE AND IMPACT OF THE STUDY: The observation that secretion of
      key components of staphylococcal virulence can be compromised by a naturally
      occurring polyphenol supports the notion that ECg and related compounds may have
      therapeutic utility for the control of infections that are currently difficult to
      treat due to the propensity of methicillin-resistant S. aureus to accumulate
      antibiotic resistance genes.

PMID- 18069980
TI  - Survey of Campylobacter jejuni in stray cats in southern Italy.
AB  - AIM: To evaluate the presence of thermotolerant Campylobacter spp. in stray cats
      in southern Italy. METHODS AND RESULTS: One hundred and thirteen animals were
      trapped in two different environments (urban area, harbour area) of the city of
      Naples. From each cat, rectal swabs were collected. The samples were processed in
      order to detect thermotolerant Campylobacter spp. by culture methods. The
      positive samples were then confirmed by multiplex polymerase chain reaction.
      Campylobacter jejuni was isolated from 19/113 (16.8%) stray cats, whereas
      Campylobacter coli was not isolated. The cat data (age, environment and sex) were
      analysed by two statistical analyses using the C. jejuni status
      (positive/negative) as a dependent variable. As regards statistical regression
      model results, age and environment were risk factors for C. jejuni positivity. In
      particular, cats older than 1 year had a significantly higher risk of being
      positive for C. jejuni than cats aged up to 1 year (OR = 10.440; P = 0.000).
      Moreover, cats living in the harbour area had a significantly higher risk to be a
      carrier of C. jejuni than cats living in urban area (OR = 17.911; P = 0.008).
      CONCLUSION: The findings of the present survey confirm stray cats as potential
      carriers of C. jejuni. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first
      study on the prevalence of C. jejuni in stray cats in Europe.

PMID- 18069981
TI  - Comparison of culture-based methods to enumerate Escherichia coli in tropical and
      temperate freshwaters.
AB  - AIMS: The specificity of a method for the enumeration of Escherichia coli
      (chromocult agar, CC) was tested using freshwater samples from a tropical area
      (Cuba Island) by isolating colonies and identifying them with API (Appareillage
      et procede d'identification) strips. Enumerations of E. coli by the most probable
      number (MPN) microplate method were compared with counts on chromogenic and
      fluorogenic agar media [CC, rapid E. coli (REC), fluorocult] in tropical and
      temperate freshwater samples. METHODS AND RESULTS: A high percentage of
      specificity (95.7%) for the CC agar enumeration of E. coli was observed. High
      regression coefficients (log-log linear regressions) were found between E. coli
      counts on agar media and by the MPN method. In the tropical environment, counts
      with REC medium were significantly different from those obtained with the other
      methods. MPN counts were found to be significantly higher than those obtained
      using the plate counts methods in the temperate environment. CONCLUSIONS:
      Escherichia coli enumeration methods based on glucuronidase activity appear to be
      suitable for the evaluation of microbiological quality in the tropical
      environment featured in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      methods for the enumeration of E. coli tested in this study should help improve
      the evaluation of microbiological contamination of Cuban freshwaters.

PMID- 18069982
TI  - Yeast identification in grape juice concentrates from Argentina.
AB  - AIMS: The purpose of this study was to identify yeast species present in spoiled
      and unspoiled grape juice concentrates from Argentine industries. METHODS AND
      RESULTS: Osmophilic and osmotolerant yeasts were isolated from spoiled--visually
      effervescent--and unspoiled--without any visible damage--grape juice concentrates
      by the spread-plate technique in two culture media. Yeast identification was done
      by classical and molecular methods. Zygosaccharomyces rouxii was the only species
      isolated from spoiled grape juice concentrates. In unspoiled samples, five
      different species were identified: Z. rouxii was isolated at a higher frequency,
      followed in decreasing order by Saccharomyces cerevisiae, Schizosaccharomyces
      pombe, Pichia anomala and Kluyveromyces delphensis. CONCLUSIONS: Yeasts isolated
      from grape juice concentrates were characterized by a limited taxonomic
      diversity, where Z. rouxii was the main species isolated. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Grape production in Argentina is mainly devoted to the industry
      where wine and grape juice concentrates represent major types of commercial
      products. Little information on common yeast contaminants is available for grape
      juice concentrates. This study constitutes the first report of osmophilic yeast
      species present in spoiled and unspoiled grape juice concentrates elaborated in
      Argentina.

PMID- 18069983
TI  - Enumeration of Salmonella from poultry carcass rinses via direct plating methods.
AB  - AIM: To evaluate direct plating methods for the estimation of Salmonella load in
      poultry carcass rinses. METHODS AND RESULTS: Two direct plating tools, the spiral
      plate count method (SPCM) and the hydrophobic grid membrane filtration (HGMF)
      method, were adapted to support quantification of Salmonella during poultry
      processing. Test samples consisted of 180 broiler carcasses from a commercial
      abattoir, 60 from each of three points in the processing line [pre-inside-outside
      bird wash (pre-IOBW), prechill and postchill]. The SPCM was used to estimate
      Salmonella load in pre-IOBW rinses, while HGMF was used to estimate Salmonella
      levels in prechill and postchill rinses. Carcass rinses were also evaluated for
      Salmonella prevalence by enrichment methods. Mean prevalences of Salmonella were
      95%, 100% and 41.7%, and the geometric mean loads were 3.7 x 10(1), 5.6 x 10(0)
      and 5.0 x 10(-2) CFU ml(-1) for pre-IOBW, prechill and postchill rinses,
      respectively. CONCLUSIONS: The methods described are useful for estimating the
      concentration of viable and typical Salmonella in poultry carcass rinses.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Direct plating enumeration methods can
      facilitate the monitoring of Salmonella load on poultry carcasses throughout the
      production process, and the evaluation of new processing intervention strategies.

PMID- 18069984
TI  - A significant role for Sigma B in the detergent stress response of Listeria
      monocytogenes.
AB  - AIMS: To investigate the contribution of the alternative sigma factor Sigma B to
      detergent stress in Listeria monocytogenes upon exposure to the surface-active
      agents, benzalkoniumchloride (BC), cetylpyridinium chloride (CPC) and sodium
      docecyl sulfate (SDS). METHODS AND RESULTS: Surfactant/detergent stress in L.
      monocytogenes 10403S and a DeltasigB mutant of 10403S was investigated by
      lethality, impact on growth and by transcriptional analysis. We observed a
      significant 1-2 log decrease in the viability of the DeltasigB mutant in response
      to lethal levels of surfactants. Transcriptional (reverse transcriptase-PCR)
      analysis revealed the induction of sigmaB by sublethal levels of surface-active
      agents. However, Sigma B does not play a significant role in the growth of L.
      monocytogenes upon exposure to sublethal levels as investigated by growth
      analysis. CONCLUSIONS: Sigma B is essential for the resistance of L.
      monocytogenes at lethal levels of BC, CPC and SDS. SIGNIFICANCE AND IMPACT OF THE
      STUDY: We demonstrate that Sigma B is essential for the resistance of the
      pathogen to surfactant stress. The findings raise the possibility that induction
      of Sigma B by sublethal levels of industrial cleaning agents may promote enhanced
      resistance of further food-processing associated stresses or conditions
      encountered during infection. Sigma B-regulated mechanisms of detergent
      resistance may provide targets for the future design of novel cleaning agents.

PMID- 18069985
TI  - Endospore dipicolinic acid detection during Bacillus thuringiensis culture.
AB  - AIMS: The aim of this work was to detect Bacillus thuringiensis endospore
      production during fermentation under conditions hindering endospore detection,
      i.e. in a complex undefined industrial medium with a high content of solids in
      suspension. METHODS AND RESULTS: Bacterial endospore production was measured
      using the photoluminescence of dipicolinate (DPA) with Tb3+. The high temperature
      and pressure of a conventional autoclave was used to release DPA from the
      endospores. The endospore was obtained from B. thuringiensis var. kurstaki HD-73
      fermentations in industrial-type media with 25.1 and 54.1 g l(-1) glucose, 4.4
      and 35.3 g l(-1) soybean meal, 5.8 g l(-1) yeast extract, 9.2 g l(-1) corn steep
      solids and mineral salts. CONCLUSIONS: In this study, we successfully determined
      the DPA concentrations during the culture of B. thuringiensis in high
      concentration soybean meal media. A good correlation was found between microscope
      endospore counting and DPA measurements in the cultures. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Because of synergy between Cry protein and endospore in B.
      thuringiensis bioinsecticides formulation, it is important to be able to
      determine endospore development during B. thuringiensis industrial-type
      fermentation, in order to ascertain the beginning of sporulation.

PMID- 18069986
TI  - Atomic property fields: generalized 3D pharmacophoric potential for automated
      ligand superposition, pharmacophore elucidation and 3D QSAR.
AB  - The atomic property fields (APF) concept is introduced as a continuous, multi
      component 3D potential that reflects preferences for various atomic properties at
      each point in space. Atomic property field-based approaches to several key
      problems in the field of ligand structure-based rational drug discovery and
      design are investigated. The superposition of ligands on one or multiple
      molecular templates is performed by Monte-Carlo minimization in the atomic
      property fields potentials combined with standard force-field energy. The
      approach is extended to multiple flexible ligand alignments using an iterative
      procedure, Self-Consistent atomic Property Fields by Optimization (SCAPFOld). The
      application of atomic property fields and SCAPFOld for virtual ligand screening
      and 3D Quantitive Structure-Activity Relationship (QSAR) is tested on published
      benchmarks. The new methods are shown to perform competitively in comparison to
      current state-of-the-art methods.

PMID- 18069987
TI  - Catalytic diamination of alkenes using N,N-dibromo-p-toluenesulfonamide as
      electrophile and nitriles as nucleophiles.
AB  - An efficient diamination reaction of alkenes has been developed for the synthesis
      of bromoalkyl-branched imidazolines by using CuI-PPh3 as the catalyst and N,N
      dibromo-p-toluenesulfonamide as the nitrogen/halogen sources. A good scope of
      alkene substrates, including alpha,beta-unsaturated ketones, alpha,beta
      unsaturated esters and simple olefins, was achieved for this reaction. Meanwhile,
      various nitriles were utilized as nucleophilic nitrogen sources. Modest to good
      yields and excellent regio- and stereoselectivity have been obtained. The
      stereochemistry was unambiguously confirmed by X-ray structural analysis. A new
      mild condition was found for the opening of resulting imidazolines by using SnCl4
      as the promoter.

PMID- 18069988
TI  - Bayesian screening for active compounds in high-dimensional chemical spaces
      combining property descriptors and molecular fingerprints.
AB  - Bayesian classifiers are increasingly being used to distinguish active from
      inactive compounds and search large databases for novel active molecules. We
      introduce an approach to directly combine the contributions of property
      descriptors and molecular fingerprints in the search for active compounds that is
      based on a Bayesian framework. Conventionally, property descriptors and
      fingerprints are used as alternative features for virtual screening methods.
      Following the approach introduced here, probability distributions of descriptor
      values and fingerprint bit settings are calculated for active and database
      molecules and the divergence between the resulting combined distributions is
      determined as a measure of biological activity. In test calculations on a large
      number of compound activity classes, this methodology was found to consistently
      perform better than similarity searching using fingerprints and multiple
      reference compounds or Bayesian screening calculations using probability
      distributions calculated only from property descriptors. These findings
      demonstrate that there is considerable synergy between different types of
      property descriptors and fingerprints in recognizing diverse structure-activity
      relationships, at least in the context of Bayesian modeling.

PMID- 18069989
TI  - Structural characterization and pharmacodynamic effects of an orally active
      11beta-hydroxysteroid dehydrogenase type 1 inhibitor.
AB  - 11Beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid action and
      inhibition of this enzyme is a viable therapeutic strategy for the treatment of
      type 2 diabetes and the metabolic syndrome. Here, we report a potent and
      selective 11beta-hydroxysteroid dehydrogenase type 1 inhibitor with a binding
      mode elucidated from the co-crystal structure with the human 11beta
      hydroxysteroid dehydrogenase type 1. The inhibitor is bound to the steroid
      binding pocket making contacts with the catalytic center and the solvent channel.
      The inhibitor binding is facilitated by two direct hydrogen bond interactions
      involving Tyrosine183 of the catalytic motif Tyr-X-X-X-Lys and Alanine172. In
      addition, the inhibitor makes many hydrophobic interactions with both the enzyme
      and the co-factor nicotinamide adenine dinucleotide phosphate (reduced). In lean
      C57BL/6 mice, the compound inhibited both the in vivo and ex vivo 11beta
      hydroxysteroid dehydrogenase type 1 activities in a dose-dependent manner. The
      inhibitory effects correlate with the plasma compound concentrations, suggesting
      that there is a clear pharmacokinetic and pharmacodynamic relationship. Moreover,
      at the same doses used in the pharmacokinetic/pharmacodynamic studies, the
      inhibitor did not cause the activation of the hypothalamic-pituitary-adrenal axis
      in an acute mouse model, suggesting that this compound exhibits biological
      effects with minimal risk of activating the hypothalamic-pituitary-adrenal axis.

PMID- 18069990
TI  - Anatomic distribution of apoptosis in medulla oblongata of infants and adults.
AB  - The aim of the study was to evaluate the distribution of apoptosis in the
      medullary nuclei of infants and adults who died of hypoxic-ischaemic injury.
      Apoptosis was studied by terminal deoxynucleotidyl transferase-mediated dUTP nick
      end-labelling (TUNEL) in brainstems from 22 adults (7 subjects who died of opiate
      intoxication, 15 who died of other hypoxic-ischaemic injury) and 10 infants. The
      nuclei examined included the hypoglossal, dorsal motor nucleus of the vagus,
      nucleus tractus solitarii, nucleus of the spinal trigeminal tract, cuneate,
      vestibular and inferior olivary nuclei. A morphometric analysis with the optical
      disector method was performed to calculate the mean percentages (+/- standard
      deviation) of TUNEL-positive neuronal and glial cells for the sample populations.
      Opiate deaths did not have higher apoptotic indices than other adult hypoxic
      ischaemic deaths. Statistically significant differences between adults and
      infants were found in the neuronal apoptotic indices of the cuneate (28.2 +/-
      16.3% vs. 6.9 +/- 8.7%), vestibular (24.7 +/- 15.0% vs. 11.3 +/- 11.4%), nucleus
      tractus solitarii (11.2 +/- 11.2% vs. 2.3 +/- 2.4%), dorsal motor nucleus of the
      vagus (6.8 +/- 8.5% vs. 0.1 +/- 0.2%) and hypoglossal (6.6 +/- 5.7% vs. 0.1 +/-
      0.2%), indicating higher resistance of the neuronal populations of these infant
      medullary nuclei to terminal hypoxic-ischaemic injury or post-mortem changes.
      Differences in neuronal apoptotic index were also statistically significant among
      nuclei, suggesting differential characteristics of survival. Nuclei with higher
      neuronal apoptotic indices were the cuneate, vestibular and nucleus of the spinal
      trigeminal tract, which are located in the lateral medullary tegmentum and share
      the same vascular supply from the posterior inferior cerebellar artery.

PMID- 18069991
TI  - The functional development of Leydig cells in a marsupial.
AB  - Leydig cells are the major source of androgen in the male mammal. We describe
      here for the first time the development of the Leydig cell in a macropodid
      marsupial, the tammar wallaby, Macropus eugenii. Leydig cells are first
      recognized morphologically 2 days after birth with the appearance of lipid
      droplets in the cytoplasm of certain interstitial cells. Lipid content closely
      matches the steroid content of the developing testis and marks the maturation of
      the steroid synthesis pathway in the tammar testis. Morphologically mature Leydig
      cells, marked by distinct mitochondria with tubular cristae and an extensive
      anastomosing network of smooth endoplasmic reticulum, are developed by day 10
      after birth - the time of peak testosterone content in perinatal tammar testes.
      The volume percentage of each cell type in the testis does not change over time
      so the growth of each cellular component keeps pace with growth of the whole
      testis. There was no morphological or quantitative evidence of a change from one
      population of Leydig cells to another in the tammar testis as has been reported
      in several other species including the rat, mouse and human. Maturation of the
      testis is also marked by the development of tight junctions between the cell
      membranes of adjacent Sertoli cells. These appear around day 30 after birth and
      coincide with the onset of mitotic arrest in male germ cells. Overall, the
      development of the Leydig cell in the tammar wallaby follows a similar pattern to
      that seen in other mammals, although the start of Leydig cell differentiation is,
      like many other organ systems in marsupials, post natal, not fetal and there
      appears to be only a single population of Leydig cells.

PMID- 18069992
TI  - Schizophrenia modifying the expression of gender identity disorder.
AB  - INTRODUCTION: According to the Brazilian Federal Medical Association,
      transsexualism is recognized as a gender identity disorder if a long-term
      diagnostic therapeutic process has demonstrated that the transposition of gender
      roles is irreversible, and if only hormonal and surgical procedures are
      appropriate to relieve the stress associated with the gender identity. Although
      such treatment will only be initiated with caution and after a long phase of
      intense diagnostic screening, the differentiation between pure identity disorders
      and transsexual feelings secondary to an ongoing psychopathologic process, such
      as schizophrenia, can be arduous for many health professionals. AIM: To report a
      case of a female patient with schizophrenia and transsexualism and the risks of a
      potential diagnostic confusion. METHOD: A 19-year-old black woman, with an 8-year
      history of undifferentiated schizophrenia and intense gender dysphoria, was
      referred for sex reassignment surgery evaluation in the Ambulatory for the
      Treatment of Sexual Disorders of the ABC Medical School. RESULT: After a more
      adequate antipsychotic treatment, her masculine behavior has persisted, but her
      desire to change her own genital organs has decreased. CONCLUSION: A better
      acceptance of the multiplicity of possible genders should neither contribute to
      inadequate interpretations of the signs and symptoms of our patients nor
      facilitate dangerous clinical or surgical recommendations.

PMID- 18069993
TI  - Transient acute neurologic sequelae of sexual activity: headache and amnesia.
AB  - INTRODUCTION: Sexual activity may on occasion be complicated by neurologic
      syndromes of headache and amnesia. These syndromes may be alarming not only to
      patients but also to medical practitioners unfamiliar with them, initiating
      inappropriate investigations or advice. AIMS: To review the clinical features,
      differential diagnosis, investigation, pathophysiology, and treatment of primary
      headache associated with sexual activity and of transient global amnesia
      precipitated by sexual activity. METHODS: Selective literature review.
      CONCLUSION: Transient headache and amnesia associated with sexual activity are
      generally benign, self-limited syndromes of presumed vascular origin. The most
      important differential diagnosis in both instances is subarachnoid hemorrhage,
      but this may be readily excluded on the basis of clinical and investigational
      findings. Reassurance, based on clear diagnosis, is the most important treatment.

PMID- 18069994
TI  - Review of the empirical evidence for a theoretical model to understand the sexual
      problems of women with a history of CSA.
AB  - INTRODUCTION: Sexual problems in women with a history of child sexual abuse (CSA)
      are relatively common but only a few studies have attempted to explain the
      mechanisms of these problems. Given the potential for a variety of factors
      associated with sexual problems in CSA survivors, the field needs a theoretical
      model to explain these difficulties. AIM: The main aim of this article was to
      illustrate a theoretical model to understand sexual problems in CSA survivors.
      Sexual problems are here grouped into hyposexual and hypersexual. A review of
      empirical studies that support this model is presented. A second aim was to
      discuss the definition of CSA adopted in research projects. METHODS: Results from
      studies targeting psychophysiologic, affective, and cognitive sexual responses
      are discussed. MAIN OUTCOME MEASURES: Vaginal photoplethismography, sexual self
      schemas, and implicit sexual associations to sexual stimuli were the focus of the
      studies reviewed. RESULTS: These studies showed that during the exposure to
      sexual stimuli, CSA survivors experienced more inhibitory responses and less
      excitatory responses than women in the comparison groups. On the other hand, in
      situations when sexual stimuli were not present, CSA survivors showed a greater
      excitation of sexual responses than women in the comparison groups. Additionally,
      CSA survivors showed a potential difficulty inhibiting intrusive sexual thoughts.
      CONCLUSIONS: The model shows promising qualities to adequately explain the hypo-
      and hypersexuality of CSA survivors. The advantages of this model over others
      include the ability to guide the selection of cognitive and behavioral
      interventions for patients presenting for treatment.

PMID- 18069995
TI  - Expression of aquaporin water channels in rat vagina: potential role in vaginal
      lubrication.
AB  - INTRODUCTION: Aquaporins (AQPs) are membrane proteins that facilitate water
      movement across biological membranes. There has been little research on the role
      of AQPs in the female sexual arousal response. AIM: The purposes of this study
      were to investigate the localization and functional roles of AQP1, AQP2, and AQP3
      in rat vagina. METHODS: Female Sprague-Dawley rats (230-240 g, N = 20) were
      anesthetized. The vaginal branch of the pelvic nerve was stimulated for 60
      seconds (10 V, 16 Hz, 0.8 ms), and the animals were sacrificed either immediately
      or 5 minutes later. The expression and cellular localization of AQP1, 2, and 3
      were determined by Western blot and immunohistochemistry of the vagina. The
      intracellular membrane and plasma membrane fractions of the proteins in vaginal
      tissue were studied by immunoblot analysis with the differential centrifugation.
      MAIN OUTCOME MEASURES: The expression and cellular localization of AQPs, and
      pelvic nerve stimulation induced translocation of AQPs in rat vaginal tissue.
      RESULTS: Immunolabeling showed that AQP1 was mainly expressed in the capillaries
      and venules of the vagina. AQP2 was expressed in the cytoplasm of the epithelium,
      and AQP3 was mainly associated with the plasma membrane of the vaginal
      epithelium. AQPs were found to be present primarily in the cytosolic fraction of
      untreated tissues. The translocation of AQP1 and 2 isoforms from the cytosolic
      compartment to the membrane compartment was observed immediately after nerve
      stimulation and had declined at 5 minutes after nerve stimulation, while the
      subcellular localization of AQP3 was not changed by nerve stimulation.
      CONCLUSIONS: These results showed a distinct localization of AQPs in the rat
      vagina. Pelvic nerve stimulation modulated short-term translocation of AQP1 and
      2. These results imply that AQPs may play an important role in vaginal
      lubrication.

PMID- 18069996
TI  - Determinants of sexual function among women with type 2 diabetes in a Nigerian
      population.
AB  - INTRODUCTION: Sexual health is an important but often neglected component of
      diabetes care. Unlike erectile dysfunction, female sexual dysfunction has not
      been well studied among Nigerian diabetics. AIMS: To assess the sexual function
      of women with diabetes, and to determine its clinical correlates. METHODS: The
      sexual performances of 51 women with type 2 diabetes mellitus attending the
      Diabetes Clinic, University of Ilorin Teaching Hospital were assessed using the
      Female Sexual Function Index (FSFI) questionnaire. The Female Sexual Function
      (FSF) scores in each domain of sexual function were then compared with those of
      39 nondiabetic controls. The associations between the FSF scores and certain
      clinical variables, as well as some diabetic complications, were also determined.
      MAIN OUTCOME MEASURES: Sexual performance of the women as measured by the FSF
      scores using the FSFI questionnaires. Results. The FSF score in the diabetic
      women was 20.5 (+/-8.3) compared with a score of 31.2 (+/-8.8) in the control (P
      value = 0.00). The FSF scores in the arousal, pain, orgasm, and overall
      satisfaction domains were all lower in the diabetic women (P value < 0.05). There
      was no significant difference in the scores for "desire" domain in the two groups
      (P value > 0.05). Women with diabetes attempted sex less frequently (P < 0.05).
      There was a negative correlation between the ages of the women and all the
      domains of sexual function (P value < 0.05). Duration of diabetes correlated
      negatively with comfort (P value = 0.04), lubrication (P = 0.03), frequency (P
      value = 0.05), as well as orgasm (P value = 0.04) domains. There was no
      significant relationship between the FSF score and body mass index, blood
      pressure, and glycemic control. There was no significant difference between the
      FSF scores of diabetic women with complications and those without (P value >
      0.05). CONCLUSIONS: Diabetes significantly impairs the sexual performance of the
      Nigerian women afflicted with the disease. Determinants of FSF include age,
      duration of diabetes illness, and presence of menopause.

PMID- 18069997
TI  - Do troponin and B-natriuretic peptide detect cardiomyopathy in transthyretin
      amyloidosis?
AB  - OBJECTIVES: Cardiomyopathy is a well known complication in familial amyloidotic
      polyneuropathy (FAP). Troponin T and B-natriuretic peptide (BNP) have been shown
      to be excellent markers for heart complications in AL-amyloidosis. The aim of the
      study was to investigate troponin T, troponin I and BNP as markers for myocardial
      damage and failure in FAP. DESIGN: Retrospective investigation of patients with
      FAP. SETTING: Tertiary referral centre. SUBJECTS: Twenty-nine patients who had
      been submitted for evaluation of FAP. INTERVENTIONS: Two-dimensional M-mode and
      Doppler echocardiography and strain echocardiographic examination. Measurement of
      Troponin T, troponin I and BNP. RESULTS: Troponin T was detectable in only three
      patients who all had abnormal interventricular septal (IVS) thickness. Troponin I
      was abnormal in six patients (21%), of which only two had an increased IVS
      thickness. The heart function was generally well preserved in the patients in
      spite of hypertrophy of the IVS in 14 patients. BNP was elevated in 22 patients
      (76%), and it correlated significantly with IVS thickness and basal septal
      strain. CONCLUSIONS: Transthyretin amyloid seems to be less harmful to myocytes
      than that of AL amyloid as evaluated by serum troponin T and I as well as by
      echocardiography. BNP appears to be a sensitive marker for cardiomyopathy in FAP,
      and could prove valuable for follow-up purposes as has been shown for AL
      amyloidosis patients.

PMID- 18069998
TI  - Reduced positive affect (anhedonia) predicts major clinical events following
      implantation of coronary-artery stents.
AB  - OBJECTIVE: Emotional distress has been related to clinical events in patients
      with coronary artery disease, but the influence of positive affect (i.e. mood
      states such as activity, joy and cheerfulness) has received little attention.
      Therefore, we wanted to investigate the role of positive affect on clinical
      outcome after percutaneous coronary intervention (PCI) with stent implantation in
      these patients. DESIGN: Prospective follow-up study. At baseline, patients from
      the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH)
      registry completed measures of positive affect, depression and anxiety post-PCI.
      Patients with reduced positive affect scored 1 SD below the mean score. SETTING:
      University Hospital; Thoraxcenter of the Department of Cardiology. SUBJECTS: 874
      patients (72% men; 62.2 +/- 10.9 years) from the RESEARCH registry. Main outcome
      measure. Death or myocardial infarction (MI) 2 years post-PCI. RESULTS: At follow
      up, there were 52 clinical events (deaths n = 27, MIs n = 25). Reduced positive
      affect and depression/anxiety were associated with poor prognosis, but reduced
      positive affect was the only independent predictor of events. The incidence of
      death/MI in adequate versus reduced positive affect patients was 4% (29/663) vs.
      11% (23/211); HR = 2.55 (95% CI 1.46-4.34, P = 0.001), adjusting for clinical
      variables. Reduced positive affect and diabetes were independent prognostic
      factors, and patients with one (HR = 2.84, 95% CI 1.58-5.10) or both (HR = 5.61,
      95% CI 2.25-13.99) of these factors had a higher risk when compared with
      nondiabetic patients with adequate positive affect, P < or = 0.003. CONCLUSIONS:
      Reduced positive affect independently predicted death/MI following stent
      implantation, and improved risk stratification above and beyond diabetes.

PMID- 18069999
TI  - Renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms are
      not associated with the risk of incident type 2 diabetes mellitus: a prospective
      cohort study.
AB  - OBJECTIVE: The renin-angiotensin system and endothelial function have both been
      implicated in the pathogenesis of type 2 diabetes. The aim of this study was to
      assess the relationship between a set of well-characterized genetic variants of
      the renin-angiotensin system and the endothelial nitric oxide synthase (NOS3)
      gene and the incidence of type 2 diabetes. DESIGN: Prospective cohort study.
      SETTING: Women's Health Study, United States. SUBJECTS: A total of 24,309
      Caucasian women free of diabetes at baseline. MAIN OUTCOME MEASURES: Six
      previously characterized single nucleotide polymorphisms (NOS3 rs1800779, NOS3
      rs3918226, NOS3 rs1799983, ACE rs1799752, AGT rs699 and AGTR rs5186) were
      genotyped. Cox proportional-hazards models were constructed to compare the
      incidence of type 2 diabetes according to the different genotypes. RESULTS:
      During a median follow-up of 10.2 years (interquartile range 9.6-10.6 years), 999
      women developed type 2 diabetes. The age-adjusted incidence rates across the six
      genotypes were very similar, and ranged from 3.7 to 4.8 cases/1000 person-years
      of follow-up. The multivariable adjusted hazard ratios (95% confidence intervals)
      for rs1800779, rs3918226, rs1799983, rs1799752, rs699, and rs5186 were 1.01 (0.92
      1.10), 1.09 (0.93-1.27), 0.95 (0.86-1.05), 1.04 (0.95-1.14), 1.08 (0.98-1.18),
      1.01 (0.91-1.11), confirming the lack of association between the genotypes and
      incident type 2 diabetes. Stratification by body mass index revealed essentially
      unchanged results. Finally, there was no association between NOS3-haplotypes and
      incident type 2 diabetes. CONCLUSION: We did not find an association between six
      well-characterized genetic polymorphisms of the renin-angiotensin system or the
      NOS3 gene and the occurrence of type 2 diabetes.

PMID- 18070000
TI  - Telomere attrition is associated with inflammation, low fetuin-A levels and high
      mortality in prevalent haemodialysis patients.
AB  - INTRODUCTION: Chronic kidney disease (CKD) predisposes to a 10- to 20-fold
      increased cardiovascular risk. Patients undergo accelerated atherogenesis and
      vascular ageing. We investigated whether telomere attrition, a marker of cell
      senescence, contributes to this increased mortality risk. METHODS: This is a
      cross-sectional study in prevalent haemodialysis patients [n = 175; 98 Males;
      median (range) age: 66 (23-86) years]. Biochemical markers of oxidative stress
      and inflammatory status were measured in relation to the patient's leucocyte
      telomere length. Overall mortality was assessed after a median of 31 (range 2-42)
      months. RESULTS: Telomere length was shorter in CKD men, despite women being
      older (average +/- SD 6.41 +/- 1.23 vs. 6.96 +/- 1.48 kb, P = 0.002). Telomere
      length was associated with age (rho = -0.18, P = 0.01), fetuin-A (rho = 0.26, P =
      0.0004), high-sensitivity C-reactive protein (rho = -0.21, P = 0.005) and IL-6
      (rho = -0.17, P = 0.02). In a multivariate logistic regression (pseudo r(2) =
      0.14), telomere length was associated with age >65 years (odds ratio: 2.11; 95%
      CI: 1.10, 4.06), sex (2.01; 1.05, 3.86), fetuin-A (1.85; 0.97, 3.50) and white
      blood cell count (2.04; 1.02, 4.09). Receiver operating characteristic curves
      identified a telomere length < 6.28 kb as a fair predictor of mortality. Finally,
      reduced telomere length was associated with increased mortality, independently of
      age, gender and inflammation (likelihood ratio 41.6, P < 0.0001), but dependently
      on fetuin-A levels. CONCLUSION: Age and male gender seem to be important
      contributors to reduced telomere length in CKD patients, possibly via persistent
      inflammation. Reduced telomere length also contributes to the mortality risk of
      these patients through pathways that could involve circulating levels of fetuin
      A.

PMID- 18070001
TI  - Endogenous ouabain and cardiomyopathy in dialysis patients.
AB  - BACKGROUND AND METHODS: Endogenous ouabain (EO) is markedly raised in patients
      with chronic renal failure. As high EO induces myocardial cell hypertrophy in
      vitro and it is associated with left ventricular hypertrophy (LVH) in essential
      hypertensives and in patients with heart failure we investigated the relationship
      between plasma EO and LV mass and geometry in 156 end-stage renal disease (ESRD)
      patients. EO was measured by a specific radioimmunoassay and by mass
      spectrometry. RESULTS: On univariate analysis, plasma EO was directly related to
      LV mass (r = 0.26, P = 0.001) and LV end diastolic volume (r = 0.25, P = 0.002)
      and these relationships held true in multiple linear regression models including
      a series of potential confounders. Patients with eccentric LVH (n = 41, i.e. 26%)
      had the highest plasma levels of EO when compared to patients with other patterns
      of LV geometry (P = 0.001). Furthermore, plasma EO had diagnostic value for
      eccentric LVH because the area under the corresponding ROC curve (68%) was
      significantly greater (P = 0.002) than the threshold of diagnostic indifference.
      In this analysis, the sensitivity was 91% and the specificity was 36%. The
      positive predictive value was 33% but EO had a remarkably high negative
      predictive value (92%) for the exclusion of eccentric hypertrophy. CONCLUSIONS:
      In ESRD patients, plasma EO is independently associated with LV mass, LV volume
      and eccentric LVH. The results of this study are compatible with the hypothesis
      that EO is involved in alterations of LV mass in ESRD.

PMID- 18070002
TI  - Beliefs, risk perceptions, and gaps in knowledge as barriers to colorectal cancer
      screening in older adults.
AB  - OBJECTIVES: To assess beliefs and perceptions of risk about colorectal cancer
      (CRC) and gaps in knowledge about screening in adults aged 65 to 89. DESIGN: A
      population-based survey. SETTING: United States. PARTICIPANTS: A total of 1,148
      respondents with no history of CRC, representing an estimated population of 31.6
      million persons, who were stratified according to screening behavior (up to date
      (n=457) vs not up to date (n=691)) and age (65-74 vs 75-89). MEASUREMENTS: The
      Health Information National Trends Survey (2003) questionnaire. RESULTS: An
      estimated 25% of adults aged 65 to 89 had not heard of the fecal occult blood
      test, 17% had not heard of sigmoidoscopy or colonoscopy, and 42% were not up to
      date with either screening modality. Not visiting a healthcare provider in the
      previous year, not knowing about tests available for colon cancer, perceiving the
      arrangements to be checked for detecting colon cancer to be difficult, and not
      having an opinion about it and its cost, were significantly associated with not
      being up to date (each P<.03). Persons who were not up to date were frequently
      unaware of the importance of CRC screening, and often reported lack of a
      provider's recommendation to be screened (>75%). Lack of knowledge and awareness
      were more prevalent in those aged 75 to 89 than those aged 65 to 74. CONCLUSION:
      Lack of knowledge and awareness and the absence of a physician's recommendation
      to be tested might explain not being up to date with CRC screening in adults in
      these age groups. These findings suggest a potential value for better
      communication between older adults and their providers regarding screening for
      CRC, when appropriate.

PMID- 18070003
TI  - Risk factors for deep vein thrombosis in older patients: a multicenter study with
      systematic compression ultrasonography in postacute care facilities in France.
AB  - OBJECTIVES: To identify risk factors for deep vein thrombosis (DVT) in older
      patients with restricted mobility or functional disability. DESIGN: Cross
      sectional. SETTING: Forty-two postacute care departments in France. PARTICIPANTS:
      Eight hundred twelve patients aged 65 and older. MEASUREMENTS: Twenty-two
      predefined characteristics were investigated, including medical and surgical risk
      factors, dependence in six basic activities of daily living (ADLs) rated using
      the Katz index, mobility, the reported value of the Timed Up and Go Test, and
      pressure ulcers. All patients underwent lower limb ultrasonography on the day of
      the cross-sectional study. RESULTS: DVT was found in 113 patients (14%, 33
      proximal DVTs (4%) and 80 isolated distal DVTs (10%)). A positive trend was found
      in the odds of DVT for higher values on the Timed Up and Go Test for patients who
      were not bedridden or confined to a chair (P=.007). In two-level multivariable
      analysis adjusting for prophylaxis against venous thromboembolism, independent
      risk factors for DVT were aged 80 and older (adjusted odds ratio (aOR)=1.71, 95%
      confidence interval (CI)=1.05-2.79), previous history of venous thromboembolism
      (aOR=2.03, 95% CI=1.06-3.87), regional or metastatic-stage cancer (aOR=2.71, 95%
      CI=1.27-5.78), dependence in more than three ADLs (aOR=2.18, 95% CI=1.38-3.45),
      and pressure ulcers (aOR=1.85, 95% CI=1.05-3.24). CONCLUSION: Severe dependence
      in basic ADLs and higher Timed Up and Go Test score are associated with greater
      odds of DVT in older patients in postacute care facilities in France.

PMID- 18070005
TI  - Kidney transplantation in elderly people: the influence of recipient comorbidity
      and living kidney donors.
AB  - OBJECTIVES: To examine the extent to which donor and recipient characteristics
      were associated with transplant outcomes in elderly kidney transplant recipients.
      DESIGN: Retrospective review. SETTING: Single university center. PARTICIPANTS:
      One thousand one hundred two patients, including 266 patients aged 60 and older.
      MEASUREMENTS: Recipient and donor characteristics and patient and graft outcomes.
      RESULTS: Of the 1,102 patients included in this study, 266 (25%) were aged 60 and
      older, and 117 (11%) were aged 67 and older. According to Cox proportional
      hazards analysis, patient survival was worse in elderly recipients, although the
      survival outcome in the oldest group (ages 68-86) was comparable with that in
      their slightly younger peers (ages 61-67). Graft function did not differ
      according to age. Comorbidity was a significant predictor of patient survival in
      elderly recipients (hazard ratio (HR)=1.17, 95% confidence interval (CI)=1.03
      1.34, P=.02) but not in the subset of elderly recipients of living donor kidneys
      (HR=1.01, 95% CI=0.8-1.3, P=.9). CONCLUSION: Older adults can achieve good
      outcomes with kidney transplantation, although in recipients with significant
      comorbid illness, careful donor selection and selective use of living donors may
      be vital to achieving good outcomes.

PMID- 18070004
TI  - Melatonin and bright-light treatment for rest-activity disruption in
      institutionalized patients with Alzheimer's disease.
AB  - OBJECTIVES: To test whether the addition of melatonin to bright-light therapy
      enhances the efficacy in treating rest-activity (circadian) disruption in
      institutionalized patients with Alzheimer's disease (AD). DESIGN: Randomized,
      controlled trial. SETTING: Two nursing homes in San Francisco, California.
      PARTICIPANTS: Fifty subjects (mean age 86) with AD. INTERVENTION: Experimental
      subjects received 1 hour of morning light exposure (> or = 2,500 lux in gaze
      direction) Monday to Friday for 10 weeks and 5 mg melatonin (LM, n=16) or placebo
      (LP, n=17) in the evening. Control subjects (n=17) received usual indoor light
      (150-200 lux). MEASUREMENTS: Nighttime sleep variables, day sleep time, day
      activity, day:night sleep ratio, and rest-activity parameters were determined
      using actigraphy. RESULTS: Linear mixed models were employed to test the primary
      study hypotheses. No significant differences in nighttime sleep variables were
      found between groups. At the end of the intervention, the LM group showed
      significant improvement in daytime somnolence as indicated by a reduction in the
      duration of daytime sleep, an increase in daytime activity, and an improvement in
      day:night sleep ratio. The LM group also evidenced a significant increase in rest
      activity rhythm amplitude and goodness of fit to the cosinor model. CONCLUSION:
      Light treatment alone did not improve nighttime sleep, daytime wake, or rest
      activity rhythm. Light treatment plus melatonin increased daytime wake time and
      activity levels and strengthened the rest-activity rhythm. Future studies should
      resolve the question of whether these improvements can be attributed to melatonin
      or whether the two zeitgebers interact to amplify efficacy.

PMID- 18070006
TI  - Providing all-inclusive care for frail elderly veterans: evaluation of three
      models of care.
AB  - Frail elderly veterans aged 55 and older who met state nursing home admission
      criteria were enrolled in one of three models of all-inclusive long-term care
      (AIC) at three Veterans Affairs (VA) medical centers (n=386). The models
      included: VA as sole care provider, VA-community partnership with a Program of
      All-inclusive Care for the Elderly (PACE), and VA as care manager with care
      provided by PACE. Healthcare use was monitored for 6 months before and 6 to 36
      months after enrollment using VA, DataPACE, and Medicare files. Hospital and
      outpatient care did not differ before and after AIC enrollment. Only 53% of VA
      sole-provider patients used adult day health care (ADHC), whereas all other
      patients used ADHC. Nursing home days increased, but permanent
      institutionalization was low. Thirty percent of participants died; of those still
      enrolled in AIC, 92% remained in the community. VA successfully implemented three
      variations of AIC and was able to keep frail elderly veterans in the community.
      Further research on providing variations of AIC in general is warranted.

PMID- 18070007
TI  - Correlates of urinary, fecal, and dual incontinence in older African-American and
      white men and women.
AB  - OBJECTIVES: To determine prevalence and correlates of urinary (UI), fecal (FI),
      and dual (DI) incontinence in community-dwelling older adults. DESIGN: Cross
      sectional, population-based in-home survey. SETTING: Three rural and two urban
      Alabama counties (1999-2001). PARTICIPANTS: Stratified random sample of 1,000
      Medicare beneficiaries aged 65 and older: 25% African-American men, 25% white
      men, 25% African-American women, 25% white women. MEASUREMENTS: UI defined as
      involuntary urine loss at least monthly; FI defined as "In the past year, have
      you had any loss of control of your bowels, even a small amount that stained the
      underwear?" Independent variables were sociodemographics, medical history, and
      activities of daily living (ADLs) excluding toileting. Multinomial logistic
      regression models were constructed using UI, FI, and DI as dependent variables.
      RESULTS: UI, FI, and DI prevalences were 27%, 6%, and 6%, respectively. White
      women had higher prevalence of UI (41.1% vs 24.6%, P<.001) and DI (18.5% vs 8.0%,
      P=.07) but not FI (4.4% vs 3.8%, P=.83) than African-American women. Men had no
      racial differences in prevalence (UI 22.2%, FI 7.7%, DI 4.6%). In women, UI, FI,
      and DI correlates included higher Charlson comorbidity score and depressive
      symptoms and greater ADL difficulty for UI and DI. In men, UI was associated with
      prostate disease and depressive symptoms; FI with chronic diarrhea, history of
      transient ischemic attack (TIA), and poor self-perceived health; and DI with
      history of TIA, foot and leg swelling, and depressive symptoms. CONCLUSION: Women
      had racial differences as well as similar correlates of incontinence subtypes,
      whereas men did not.

PMID- 18070009
TI  - Brush border enzyme activities in relation to histological lesion in pediatric
      celiac disease.
AB  - BACKGROUND AND AIM: In celiac disease (CD), abnormalities of brush border enzyme
      activities have been detected in the course of the disease activity. There are
      conflicting results on intestinal mucosal enzyme activities and its correlation
      to mucosal injury in CD. The aim of the present study was to evaluate the brush
      border enzyme activities (disaccharidases and alkaline phosphatase) in the
      duodenal mucosa of North Indian children with CD and to examine their correlation
      to duodenal mucosal morphological alterations. METHODS: This prospective study
      included 71 children with CD and 29 controls (patients with gastroesophageal
      reflux disease) in whom upper gastrointestinal endoscopy was performed and distal
      duodenal biopsies were taken for histological assessment, and estimation of
      disaccharidases and alkaline phosphatase activities. Each biopsy sample was
      classified according to the modified Oberhuber classification. Lactase, sucrase,
      maltase and alkaline phosphatase activities were estimated in duodenal biopsy
      homogenates from patients with CD and from controls. The association between
      enzyme activities and duodenal morphology was examined. RESULTS: The mean age of
      the 71 patients with CD (M:F, 43:28) was 6.0 +/- 0.3 years and mean age of onset
      of symptoms was 2.7 +/- 0.4 years. Sixty-four of 71 (90.1%) CD patients showed
      type 3 (destructive) lesion, whereas it was grade 0 in all patients with
      gastroesophageal reflux disease. In CD and patients with gastroesophageal reflux
      disease, the mean level (IU/g protein) of lactase was 12.1 +/- 0.9 versus 24.4 +/
      1.0 (P < 0.001), mean level of sucrase was 25.9 +/- 1.9 versus 42.5 +/- 1.9 (P <
      0.001), mean level of maltase was 56.6 +/- 3.5 versus 76.1 +/- 13.0 (NS), and
      mean level of alkaline phosphatase was 602.8 +/- 56.2 versus 1359.3 +/- 51.2 (P <
      0.001), respectively. The mean disaccharidases and alkaline phosphatase levels
      were not significantly different in patients with milder lesions (type 2 and type
      3a) compared with those of control. However, mean lactase, sucrase and alkaline
      phosphatase levels were significantly lower (P < 0.001) in CD patients with
      moderate (type 3b) and severe (type 3c) lesions compared with control.
      CONCLUSIONS: A generalized decrease of disaccharidases and alkaline phosphatase
      activity was seen in the duodenal mucosa of children with CD. The depressed
      activities of lactase, sucrase and alkaline phosphatase were well correlated with
      the histological grade of duodenal mucosal lesions in children with CD.

PMID- 18070008
TI  - Diagnostic value of magnetic resonance cholangiopancreatography for clinically
      suspicious spontaneous passage of bile duct stones.
AB  - BACKGROUND AND AIM: We investigated the usefulness of magnetic resonance
      cholangiopancreatography (MRCP) and the need for endoscopic retrograde
      cholangiopancreatography (ERCP) in patients with clinically suspicious
      spontaneous passage of bile duct stones. METHODS: The study population consisted
      of 113 patients suspected of having common duct bile stones. Of them, 50 patients
      were clinically suspected of spontaneous passage of bile duct stones based on the
      presence of gallbladder stones on ultrasound examination or a history of common
      bile duct stones after cholecystectomy, clinical symptoms including abdominal
      pain and fever associated with inflammatory reaction and marked rise of
      hepatobiliary enzymes which resolved or normalized after conservative treatment
      without evidence of stones in the common bile duct on MRCP. These 50 patients
      were prospectively followed up for a median of 10.2 months. RESULTS: All patients
      except for one had had no symptoms related to cholangitis. Only one patient
      received ERCP due to recurrence of symptoms after 6 months. CONCLUSION: When
      clinical symptoms improve, hematological parameters normalize, and MRCP indicates
      that there are no stones in the common bile duct, it can be considered that the
      stones have passed naturally.

PMID- 18070010
TI  - Endoscopic mucosal resection: not only therapeutic, but a diagnostic procedure
      for sessile gastric polyps.
AB  - BACKGROUND AND AIMS: Histological examination of specimens obtained by forceps
      biopsy sampling of gastric lesions is of limited accuracy, and their management
      on this basis is therefore controversial. Endoscopic mucosal resection (EMR) was
      initially developed in Japan for the resection of early gastric cancer (EGC). The
      potential use of EMR as a diagnostic tool has been suggested. The aims of the
      present study were to assess the value of forceps biopsy sampling in establishing
      the correct diagnosis revealed by EMR and to evaluate the efficacy of EMR.
      METHODS: Fifty-six subjects with sessile gastric polyps of epithelial origin, at
      least 0.5 cm in diameter, and not associated with polyposis syndromes, were
      included. Following forceps biopsy sampling, EMR was performed with an inject-and
      cut technique or with cap-fitted methods. The histological results on the forceps
      biopsy and the resected specimens were analyzed. RESULTS: Histology on the
      resected specimens revealed neoplastic lesions in 34 cases, including seven EGC,
      and there were hyperplastic-inflammatory lesions in 21 cases. Complete agreement
      between the previous histological results of the forceps biopsy samples and the
      resected specimens was seen in only 76.7% of the lesions. Altogether, the
      sensitivity and specificity of the forceps biopsy procedure for diagnosing
      neoplastic lesions were 87.5% (95% confidence interval [CI] = 76.0-98.9%) and
      65.2% (95% CI = 45.7-84.7), respectively. A clinically relevant discrimination
      between neoplastic and non-neoplastic lesions was not achieved in seven cases. No
      complications, such as perforation or massive bleeding necessitating surgical
      treatment, were encountered. EMR was considered complete in five patients. None
      of the EGC recurred during the mean 38-month (6-72) follow up. CONCLUSIONS:
      Forceps biopsy is not fully representative of the entire lesion, and a simple
      biopsy may therefore lead to a faulty differentiation between neoplastic and non
      neoplastic lesions. EMR proposes diagnostic and staging advantage in assessing
      patients with EGC as compared to forceps biopsy, because it provides more intact
      mucosa and submucosa for histological analysis. Sessile gastric polyps should be
      fully resected by EMR for a final diagnosis and (depending on the lesion size and
      type) possibly definitive treatment.

PMID- 18070011
TI  - Expression of Toll-like receptor 4 in various organs in rats with D-galactosamine
      induced acute hepatic failure.
AB  - BACKGROUND AND AIMS: Activation of the pro-inflammatory cytokine cascade,
      including tumor necrosis factor alpha (TNF-alpha) is considered to play an
      important role in the pathophysiology and clinical outcome of severe liver
      injury. Kupffer cells, resident macrophages of the liver, have a transmembrane
      protein Toll-like receptor 4 (TLR4), which recognizes endotoxin
      (lipopolysaccharide; LPS) or LPS-CD14 complex and mediates macrophage activation
      and pro-inflammatory cytokine release. D-Galactosamine (GalN), a hepatocyte
      specific inhibitor of RNA synthesis, is known to sensitize animals to the lethal
      effects of LPS and TNF-alpha. In the present study we seek to address TLR4
      signaling in the development of GalN-induced acute hepatic failure (AHF) and
      explore the expression of TLR4 mRNA as compared to TNF-alpha mRNA and CD14 mRNA
      in the liver, spleen and lung of rats with GalN-induced hepatitis. METHODS: AHF
      was induced in male Wistar rats by the intraperitoneal injection of 1 g/kg
      bodyweight GalN. Expression levels of TNF-alpha, TLR4 and CD14 mRNA in the whole
      liver, spleen and lung of rats were detected by reverse transcription-polymerase
      chain reaction analysis. RESULTS: Expression level of TLR4 mRNA in the liver of
      rats with GalN-induced AHF was increased parallel with that of TNF-alpha and CD14
      mRNA as compared to the control rats. However, expression levels of TNF-alpha,
      TLR4 and CD14 mRNA in the whole spleen and lung were not different between rats
      with AHF and control. CONCLUSIONS: There may be a difference of stimulatory
      effects of endotoxin on the innate immunity between the liver and other organs of
      rats with GalN-induced AHF.

PMID- 18070012
TI  - Psychological comorbidity and complexity of gastrointestinal symptoms in
      clinically diagnosed irritable bowel syndrome patients.
AB  - BACKGROUND AND AIM: The prevalence of psychological disorders is high in patients
      with irritable bowel syndrome (IBS) but their role in symptom reporting is
      uncertain. It is thus interesting whether the number of functional
      gastrointestinal disorders (FGID) determines the load of psychological
      comorbidity. The Rome III criteria have not been used to evaluate such a
      relationship as yet. Moreover, not many studies have examined the sensitivity of
      the Rome III criteria in detecting IBS. Our aims were therefore: (i) to determine
      whether those IBS participants with more FGID had a tendency to greater
      psychological comorbidity than those with fewer FGID; and (ii) to assess the
      performance of the Rome III criteria in detecting IBS versus the diagnosis of the
      gastroenterologist. METHODS: A cross-sectional survey of 32 consecutive
      outpatients with clinically diagnosed IBS was performed. The Hospital Anxiety and
      Depression Scale (HADS), the Short Form 12 Health Survey (SF-12), and the Rome
      III criteria questionnaire (BDQ-6) were administered. Multiple linear regression
      was conducted to detect associations among FGID, anxiety, depression and quality
      of life. RESULTS: Overall, 50% of participants were anxious and 12% were
      depressed. Forty-four percent of participants had >two FGID; however, the number
      of FGID did not correlate with scores for anxiety, depression or quality of life.
      Amazingly, only 50% (CI: 33-67) of participants clinically diagnosed with IBS met
      Rome III criteria for IBS. CONCLUSION: Contrary to our expectations, a greater
      load of FGID did not correlate with a greater load of psychological comorbidity.
      Surprisingly, the Rome III criteria detected only 50% of clinical cases of IBS.

PMID- 18070013
TI  - Liposome-mediated gene transfer of endothelial nitric oxide synthase to cirrhotic
      rat liver decreases intrahepatic vascular resistance.
AB  - BACKGROUND AND AIMS: Nitric oxide (NO) production by endothelial nitric oxide
      synthase (eNOS) in sinusoidal endothelial cells is reduced in the injured liver
      and leads to intrahepatic portal hypertension. The present study evaluates the
      effects of liposome-mediated gene transfer of eNOS on the intrahepatic vascular
      resistance and portal venous pressure (PVP) in cirrhotic rats. METHODS: Hepatic
      cirrhosis was induced in male Sprague-Dawley rats by intraperitoneal injection of
      carbon tetrachloride (CCl(4)), whereas the control normal rats were given the
      same dose of peanut oil. Plasmid eukaryotic expression vector (liposome
      pcDNA3/eNOS) was injected into the portal vein of CCl(4) cirrhotic rats, whereas
      cirrhotic controls received the same dose of naked plasmid (liposome-pcDNA3) or
      Tris buffer, and control normal rats received the same dose of Tris buffer. Five
      days after gene transfer, the levels of eNOS mRNA and protein, NO production, PVP
      and the changes of hepatic intrahepatic vascular resistance were investigated.
      RESULTS: Five days after eNOS gene transfer, the levels of eNOS mRNA, eNOS
      protein and NO production in cirrhotic rats increased remarkably, while hepatic
      vascular resistance and PVP decreased significantly in cirrhotic rats.
      CONCLUSION: Liposome-mediated eNOS gene transfer via intraportal injection is
      feasible and the increase of intrahepatic eNOS leads to a marked decrease in
      introhepatic vascular resistance and PVP. These data indicate that intrahepatic
      eNOS plays an important role in the pathogenesis of portal hypertension and gene
      transfer of eNOS is a potential and novel therapy for portal hypertension.

PMID- 18070014
TI  - Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized
      asymptomatic patients with hepatitis B virus-related chronic liver disease.
AB  - BACKGROUND AND AIM: Hepatitis E virus (HEV) has recently been implicated in
      episodes of acute decompensation in patients having underlying chronic liver
      disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation
      of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected
      patients is less well described. The aim of the present study was to investigate
      the etiology of acute exacerbation of previously asymptomatic and unrecognized
      HBV-infected patients and to evaluate the relative role of HEV. We also
      investigated the effect of superinfection on the clinical spectrum of underlying
      HBV infection. METHODS: Forty-three patients presented with the following were
      retrospectively analyzed: (i) clinical features suggestive of acute hepatitis;
      (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core
      antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no
      features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least
      12 months on follow up; and (vii) having a follow-up biopsy during the
      convalescent phase showing evidence of chronic hepatitis B. RESULTS: Of the 43
      patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2)
      at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis
      A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6%
      hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%)
      patients had spontaneous exacerbation (immune clearance with spontaneous
      seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous
      exacerbation (due to reactivation). Overall, HEV superinfection contributed to
      20% of acute exacerbation episodes and, in particular, 36% of episodes in
      initially HBeAg (-) patients. Time to alanine aminotransferase normalization was
      longer in patients with superinfection (n = 13) as compared to spontaneous
      exacerbation (n = 30) (median [range] 36 [8-48]vs 16 [6-36] weeks, P = 0.001).
      During convalescence, there was no significant difference between histological
      activity index score (median [range] 8 [4-11]vs 8 [4-16] weeks, P = 0.629) and
      fibrosis scores (median [range] 3.5 [1-4]vs 2 [1-4] weeks, P = 0.099] on liver
      biopsy after recovery among patients with acute exacerbation due to
      superinfection and spontaneous exacerbation. CONCLUSIONS: Acute exacerbations in
      HBeAg (+) patients are most often due to spontaneous viral activation, while in
      HBeAg (-) patients, superinfection with non-B hepatitis viruses and spontaneous
      viral activation are equally common. HEV is an important cause of acute
      exacerbation in previously asymptomatic and unrecognized patients with HBV
      related CLD.

PMID- 18070015
TI  - Gallstones and Clonorchis sinensis infection: a hospital-based case-control study
      in Korea.
AB  - BACKGROUND AND AIM: A high prevalence of intrahepatic stones in some areas of
      East Asia has been believed to be related with Clonorchis sinensis infection. The
      authors conducted a hospital-based case-control study to evaluate the role of
      Clonorchis sinensis infection as a risk factor for the development of gallstones
      in Korea. METHODS: The cases of 138 patients with gallstones (intrahepatic 44,
      gallbladder 67, and extrahepatic 27) and matched controls underwent microscopy
      for C. sinensis, serological tests for C. sinensis using enzyme-linked
      immunosorbent assay, radiological examinations, and interviews concerning the
      history of eating raw freshwater fish. We assessed a relationship of three types
      of gallstones and variables regarding C. sinensis by using univariate and
      multivariate statistical analyses. RESULTS: Univariate statistical analyses
      showed that radiological evidence of C. sinensis and recent history of eating raw
      freshwater fish were related to an increased risk of intrahepatic stones (P =
      0.0002 and 0.0039, respectively). According to multivariate statistical analyses,
      radiological evidence of C. sinensis was the only risk factor for intrahepatic
      stones (odds ratio = 7.835; 95% confidence interval = 1.671-36.724). Any evidence
      regarding C. sinensis was not related to an increased risk of either gallbladder
      or extrahepatic stones. CONCLUSION: Radiological evidence of C. sinensis was
      significantly associated with intrahepatic stones.

PMID- 18070016
TI  - Gene expression of AGS cells stimulated with released proteins by Helicobacter
      pylori.
AB  - BACKGROUND AND AIM: Interactions between released proteins by Helicobacter pylori
      (H. pylori) and the cells of gastric epithelium to which it adheres may
      contribute to gastric inflammation and epithelial damage. The present study was
      performed to evaluate the gene expression of AGS gastric cancer cells stimulated
      with released proteins by H. pylori. METHODS: Gene expression of AGS cells to the
      stimulation by H. pylori-released proteins (G27 strain) were monitored using
      oligonucleotide microarrays. RESULTS: Eighty-eight genes (0.88%) and eight genes
      (0.08%) were up- or downregulated, respectively, by treating AGS cells with H.
      pylori-released proteins but not by H. pylori adhesion after 12 h of coculture.
      Out of the selected 40 up- and five downregulated genes, 29 upregulated genes
      classified as general RNA polymerase II transcription factor activity (GTF2B,
      PPARGC1A), SH3/SH2 adaptor activity (CRKL), transferase activity (ACLY, CRKL,
      PIGC, PLK4), and oxidoreductase activity (IDH1) were confirmed to be upregulated
      by released proteins and not by H. pylori adhesion by real-time reverse
      transcription-polymerase chain reaction. When the concentrated H. pylori-cultured
      supernatant prepared by our protocol was treated by boiling, the upregulations of
      26 of these 29 genes (89.7%) except for CD160, ZNF268, and PSAT1 disappeared.
      This confirmed that most of these upregulations were caused by released proteins.
      CONCLUSION: Host genes involving transcription, signaling and stress are
      significantly modulated by the proteins released by H. pylori. This might
      strengthen the gastroduodenal pathogenesis induced by H. pylori.

PMID- 18070017
TI  - Eosinophilic esophagitis in children with celiac disease.
AB  - BACKGROUND AND AIMS: Eosinophilic esophagitis and celiac disease are distinct
      gastrointestinal disorders. The present study in children highlights the possible
      coexistence of these two conditions. This study also analyzes the epidemiological
      and clinical profiles of these patients. METHODS: The medical records of patients
      diagnosed with celiac disease from 1 April 1999 to 31 March 2007 were reviewed.
      Patients with coincident histological diagnosis of eosinophilic esophagitis were
      retrospectively identified. The presenting symptoms, laboratory evaluations,
      endoscopic and histopathological findings, and treatment and follow-up outcomes
      of these patients were analyzed. RESULTS: Of the 221 patients with celiac
      disease, seven (3.2%) were also diagnosed with eosinophilic esophagitis. A
      majority (6/7) presented with periumbilical pain and diarrhea. None had
      dysphagia. Each patient had abnormal celiac screening tests. Three patients had
      peripheral blood eosinophilia and elevated eosinophil cationic protein.
      Endoscopic changes of eosinophilic esophagitis and celiac disease were apparent
      in the majority of patients (6/7). A gluten-free diet was instituted in every
      patient. Topical corticosteroid therapy was started in one patient at diagnosis
      and in another patient after repeat endoscopic and histopathological evaluations.
      CONCLUSIONS: Awareness of the potential coexistence of eosinophilic esophagitis
      and celiac disease should promote optimal diagnosis of these conditions. Routine
      esophageal biopsies may be warranted when investigating for celiac disease.

PMID- 18070018
TI  - Peripheral blood eosinophilia in association with generalized pustular and
      erythrodermic psoriasis.
AB  - BACKGROUND: In recent studies, it has been documented that the eosinophil cells
      play active role in many kinds of inflammatory disorders. Measurements of the
      mediators released by eosinophils and cell counts in serum and skin have provided
      some evidence indicating the role of eosinophils in psoriasis. OBJECTIVE: To
      evaluate the blood eosinophil cell count in patients with erythrodermic psoriasis
      and generalized pustular psoriasis. METHODS: In this study, 48 patients with
      histopathologically proven psoriasis (33 with erythrodermic, 15 with generalized
      pustular); 43 patients with maculopapular, erythematous, or bullous drug eruption
      with widespread involvement; and 51 patients with basal cell carcinoma were
      included. These three groups were compared with each other in terms of their
      absolute eosinophil cell counts and percentage of eosinophils. RESULTS: Forty-one
      point seven per cent of patients with psoriasis had peripheral blood eosinophilia
      compared with 58.1% of the patients with drug eruption and 11.8% of patients with
      basal cell carcinoma. The percentage of patients with eosinophilia both in
      patients suffering from psoriasis and drug eruption were significantly increased
      compared with the patients with basal cell carcinoma (P < 0.001). The absolute
      median eosinophil cell counts both in patients with psoriasis and drug eruption
      were also significantly differed from patients with basal cell carcinoma (259.2,
      439.1 and 183.1, respectively; P < 0.001) CONCLUSIONS: Peripheral blood
      eosinophilia seems to be associated with severe forms of psoriasis. This finding
      may suggest that the eosinophils have significant roles in the pathogenesis of
      these types of psoriasis.

PMID- 18070019
TI  - Pamidronate as a treatment option in calciphylaxis.

PMID- 18070020
TI  - Late manifestation of dyskeratosis congenita presenting as chronic dermal ulcer
      in a 37-year-old man.

PMID- 18070021
TI  - Urticarial vasculitis with haemorrhagic vesicles successfully treated with
      reserpine.

PMID- 18070022
TI  - Embolia cutis medicamentosa following thiocolchicoside injection.

PMID- 18070023
TI  - Nodular hidradenoma masquerading an epidermal cyst.

PMID- 18070024
TI  - Cutaneous manifestations in relation to immunologic parameters in a cohort of
      primary myelodysplastic syndrome patients.
AB  - BACKGROUND: Cutaneous lesions in myelodysplastic syndrome (MDS) may be specific
      or not and may reveal bone marrow transformation. Our purpose was to investigate
      in a cohort of 84 MDS patients the correlation of cutaneous findings with
      immunologic parameters and prognostic features of MDS in order to clarify their
      potential clinical significance. MATERIALS AND METHODS: We studied a cohort of 84
      newly diagnosed MDS patients in order to assess the cutaneous findings present at
      the time of diagnosis and during 1 to 3 years of follow-up. We described the
      clinical variety of cutaneous findings ascertained by histology. We also looked
      for any association between the group of MDS patients with skin manifestations
      and MDS subtype, immunologic and prognostic features highlighting transformation
      to acute leukaemia. RESULTS: Twenty-one patients presented cutaneous
      manifestations: 1 patient developed leukaemia cutis, 6 patients photosensitivity
      not associated with autoimmune disease, 3 prurigo nodularis, 2 Sweet's syndrome,
      6 leucocytoclastic vasculitis, 2 ecchymoses and purpura associated with
      preexisting relapsing polychondritis, 1 patient subcutaneous nodules associated
      with Wegener's granulomatosis and 1 patient with malar rash and oral ulcers
      associated with preexisting systemic lupus erythematosus. Adjusted for age and
      gender, the presence of skin findings constitutes a significant predictor of the
      high-risk MDS subgroup (odds ratio, 3.59; 95% confidence interval, 1.18-10.92).
      Hypergammaglobulinemia was significantly higher in the MDS subgroup with skin
      manifestations (P = 0.03). CONCLUSION: Most MDS patients with cutaneous
      manifestations belong to the high-risk MDS subgroup and present
      hypergammaglobulinemia. Early biopsy of skin lesions in myelodysplasia is
      indicated.

PMID- 18070025
TI  - Late adverse effects after soft X-ray therapy of cutaneous malignancies:
      pruritus, burning, epiphora and insufficient occlusion of the mouth.
AB  - BACKGROUND: Pruritus, burning, epiphora and insufficient occlusion of the mouth
      have been less extensively studied than cosmetic changes in irradiated fields.
      OBJECTIVES: How frequent are these late adverse effects? Do they usually occur
      permanently? Are they influenced by treatment and tumour parameters, sex and age
      of the patients? METHODS: Patients were interviewed at least once later than 90
      days after soft X-ray therapy. RESULTS: Pruritus has been reported in 18.5% of
      the interviews, burning in 7.7%, epiphora in 36.2% and insufficient occlusion of
      the mouth in 11.5%. Patients were usually not permanently troubled and irritated
      by these symptoms: pruritus more than once per week was reported in every
      interview for 0.6% of the fields, burning for 0.2%, epiphora for 6.4% and
      insufficient occlusion for 0%. Irritation by these symptoms has been stated in
      every interview for 5.1% of fields around the eye and for 1.4% of fields at other
      sites. Late pruritus, burning and epiphora were less frequently reported after
      irradiation with lower total doses, lower time-dose-fractionation factor (TDF)
      and by men. Patients older than 70 years of age experienced pruritus and burning
      less frequently. The largest diameter of the irradiated field influenced pruritus
      and the half value depth of the X-rays influenced burning and epiphora.
      CONCLUSIONS: Late pruritus, burning, epiphora and insufficient occlusion of the
      mouth do not considerably reduce the value of soft X-ray therapy because these
      adverse effects usually are not experienced permanently. Total dose and TDF
      should not be chosen higher than necessary.

PMID- 18070026
TI  - Once-weekly treatment of vitiligo with monochromatic excimer light 308 nm in
      Chinese patients.

PMID- 18070027
TI  - Triple antiretroviral therapy improves psoriasis associated with human
      immunodeficiency virus infection: a clinico-therapeutic experience.

PMID- 18070028
TI  - 'Mucocutaneous' or 'cutaneomucosal' interval: which one is longer in pemphigus
      vulgaris?

PMID- 18070029
TI  - Cutaneous Munchausen's syndrome caused by self-injections of fermented beans.

PMID- 18070030
TI  - Translating innate response into long-lasting antibody response by the intrinsic
      antigen-adjuvant properties of papaya mosaic virus.
AB  - Identifying the properties of a molecule involved in the efficient activation of
      the innate and adaptive immune responses that lead to long-lasting immunity is
      crucial for vaccine and adjuvant development. Here we show that the papaya mosaic
      virus (PapMV) is recognized by the immune system as a pathogen-associated
      molecular pattern (PAMP) and as an antigen in mice (Pamptigen). A single
      immunization of PapMV without added adjuvant efficiently induced both cellular
      and specific long-lasting antibody responses. PapMV also efficiently activated
      innate immune responses, as shown by the induction of lipid raft aggregation,
      secretion of pro-inflammatory cytokines, up-regulation of co-stimulatory
      molecules on dendritic cells and macrophages, and long-lasting adjuvant effects
      upon the specific antibody responses to model antigens. PapMV mixed with
      Salmonella enterica serovar Typhi (S. typhi) outer membrane protein C increased
      its protective capacity against challenge with S. typhi, revealing the intrinsic
      adjuvant properties of PapMV in the induction of immunity. Antigen-presenting
      cells loaded with PapMV efficiently induced antibody responses in vivo, which may
      link the innate and adaptive responses observed. PapMV recognition as a Pamptigen
      might be translated into long-lasting antibody responses and protection observed.
      These properties could be used in the development of new vaccine platforms.

PMID- 18070031
TI  - Noradrenaline reduces ischemia-induced arrhythmia in anesthetized rats:
      involvement of alpha1-adrenoceptors and mitochondrial K ATP channels.
AB  - INTRODUCTION: We have evaluated the part played by the mitochondrial ATP
      sensitive potassium (mK(ATP)) channels on effect of alpha(1)-adrenoceptor
      activation by noradrenaline in ischemia-induced ventricular arrhythmia. METHODS
      AND RESULTS: Anesthetized rats were subjected to 25 minutes of regional ischemia,
      and infarct size (IS) and ischemia-induced ventricular arrhythmia were measured.
      Group I served as saline control with ischemia (n = 9). In group II (n = 9), the
      ischemic period was preceded by three short episodes of ischemia, followed by
      reperfusion. In group III, noradrenaline (2 microg/kg, IV, n = 9) was injected
      prior to ischemia. In group IV, an alpha(1)-adrenoceptor blocker (prazosin, 0.5
      mg/kg, IV, n = 6) was administrated prior to noradrenaline injection. In Groups V
      and VI, rats received a specific mitochondrial K(ATP) channel inhibitor [5
      hydroxydecanoic acid (5-HD), 10 mg/kg, IV, n = 6] prior to or after noradrenaline
      injection. Ischemic preconditioning (IPC) and noradrenaline markedly reduced
      incidences of ventricular fibrillation (VF) (0%, 0% vs. 55.5% in control, P <
      0.05) and ventricular tachycardia (VT) (11%, 44.5% vs. 100% in control, P < 0.001
      and P < 0.05), duration of VF + VT (3 +/- 1 seconds, 4.7 +/- 2.1 seconds vs. 52.9
      +/- 6 seconds in control, P < 0.001), number of VF + VT episodes (1.7 +/- 1.7,
      5.75 +/- 2.4 vs. 60.5 +/- 8 in control, P < 0.001), severity of arrhythmias (0.3
      +/- 0.3, 1.7 +/- 0.5 vs. 3.9 +/- 0.3 in control rats, P < 0.001 and P < 0.01),
      and IS (13.6 +/- 1.8%, 18.2 +/- 1.5% vs. 49.6 +/- 2.4% in control, P < 0.001).
      Administration of prazosin or 5-HD prior to or after noradrenaline injection
      intensified incidences of VF (66.6%, 66.6% and 50%, P < 0.05) and VT (100%, 100%,
      and 100%, P < 0.05), duration of VF + VT episodes (70.2 +/- 10.5 seconds, 69.8 +/
      6.75 seconds, and 60.8 +/- 14.9 seconds, P < 0.001), number of VF + VT episodes
      (56 +/- 16.4, 67 +/- 11, and 45 +/- 3.5, P < 0.01, P < 0.001, and P < 0.05),
      severity of arrhythmias(3.8 +/- 0.3, 4 +/- 0.5, and 3.7 +/- 0.2, P < 0.01, P <
      0.05, and P < 0.01), and IS (45.5 +/- 3%, 46.8 +/- 3.4%, and 43 +/- 2.5%,
      respectively, P < 0.001) compared with the noradrenaline-treated group.
      CONCLUSION: Prazosin or 5-HD treatment eliminated the beneficial effects of
      noradrenaline on arrhythmogenesis and infarct size.

PMID- 18070032
TI  - Luminescence, virulence and quorum sensing signal production by pathogenic Vibrio
      campbellii and Vibrio harveyi isolates.
AB  - AIMS: To study the relationship between luminescence, autoinducer production and
      virulence of pathogenic vibrios. METHODS AND RESULTS: Luminescence, quorum
      sensing signal production and virulence towards brine shrimp nauplii of 13 Vibrio
      campbellii and Vibrio harveyi strains were studied. Although only two of the
      tested strains were brightly luminescent, all of them were shown to produce the
      three different types of quorum sensing signals known to be produced by Vibrio
      harveyi. Cell-free culture fluids of all strains significantly induced
      bioluminescence in the cholerae autoinducer 1, autoinducer 2 and harveyi
      autoinducer 1 reporter strains JAF375, JMH597 and JMH612, respectively. There was
      no relation between luminescence and signal production and virulence towards
      brine shrimp. CONCLUSIONS: There is a large difference between different strains
      of Vibrio campbellii and Vibrio harveyi with respect to bioluminescence. However,
      this is not reflected in signal production and virulence towards gnotobiotic
      brine shrimp. Moreover, there seems to be no relation between quorum sensing
      signal production and virulence towards brine shrimp. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The results presented here indicate that strains that are most
      brightly luminescent are not necessarily the most virulent ones and that the
      lower virulence of some of the strains is not due to a lack of autoinducer
      production.

PMID- 18070033
TI  - Effect of ante- and postmortem hide clipping on the microbiological quality and
      safety and ultimate pH value of beef carcasses in an EC-approved abattoir.
AB  - AIMS: Effect of ante- and postmortem hide clipping on the microbiological quality
      of beef carcasses. METHODS AND RESULTS: Bovine carcasses (362) were tested for
      indicator micro-organisms and the presence of pathogens. Prior to slaughter, hide
      cleanliness of each animal was categorized on a scale of 1-5 (clean to dirty).
      Lowest mean aerobic colony counts (ACC) (log(10) 3.0 CFU cm(-2)) came from
      carcasses where clipping had been performed in lairage, antemortem. ACC from
      animals clipped online (log(10) 3.2 CFU cm(-2)) were significantly higher (P <
      0.05) than those clipped in lairage, but comparable to those carcasses from
      Category 1 and 2 animals. There were no significant differences in the detection
      of pathogens from any of the carcass groups. Ultimate pH values for carcasses
      from Category 3 and 4 animals showed clipping animals in lairage, as opposed to
      online, resulted in a small, but significant increase (P < 0.05) in pH value
      (mean pH 5.66 and 5.59, respectively). CONCLUSIONS: Hide clipping does not
      adversely affect microbiological quality of carcasses, although higher ultimate
      pH values indicate increases in antemortem stress. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Hide clipping carcasses both ante- and postmortem appears to be an
      effective intervention to minimize transfer of hide microflora to carcasses
      during slaughtering operations. Online clipping offers advantages for animal
      welfare and improves safety for operatives.

PMID- 18070034
TI  - Development of detection medium for hard-to-culture beer-spoilage lactic acid
      bacteria.
AB  - AIMS: To develop a detection medium for hard-to-culture beer-spoilage lactic acid
      bacteria (LAB). METHODS AND RESULTS: Four hard-to-culture beer-spoilage strains
      of LAB, belonging to Lactobacillus paracollinoides and Lactobacillus lindneri,
      have been obtained by repeatedly subculturing the wild-type strains in beer. To
      develop a countermeasure against these hard-to-culture beer-spoilage LAB, a beer
      based medium was modified. As a consequence, the supplementation of a small
      amount of de Man Rogosa Sharpe medium was found to enhance the growth of hard-to
      culture beer-spoilage LAB strains obtained in this study. In addition, sodium
      acetate was shown to improve the selectivity of this beer-based medium. Further
      comparative study was performed with five other media widely used for the
      detection of beer-spoilage LAB in the brewing industry. This study revealed that
      the newly developed medium, designated advanced beer-spoiler detection (ABD)
      medium, possessed superior sensitivity for hard-to-culture beer-spoilage LAB and
      comparable sensitivity with easy-to-culture beer-spoilage LAB. Moreover, ABD
      medium was found to suppress the growth of nonspoilage micro-organisms, and
      thereby allow the selective growth of beer-spoilage LAB. CONCLUSIONS: Advanced
      beer-spoiler detection medium is considered as an effective tool for
      comprehensive detection of beer-spoilage LAB in breweries. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The detection by ABD medium can be used as an indicator for
      differentiating the beer-spoilage ability of LAB without further confirmatory
      tests in breweries.

PMID- 18070035
TI  - Strain-specific detection of two Aureobasidium pullulans strains, fungal
      biocontrol agents of fire blight by new, developed multiplex-PCR.
AB  - AIM: The aim of this study was to develop a specific and sensitive identification
      method for two Aureobasidium pullulans biocontrol strains, CF10 and CF40, based
      on a sequence-characterized amplified region (SCAR) derived from RAPD - and
      multiplex-RAPD PCR analysis. METHODS AND RESULTS: The random amplified
      polymorphic DNA (RAPD) and multiplex RAPD-PCR techniques were used for a
      preliminary screening of A. pullulans genetic variability among 200 isolates.
      This approach allowed the selection of ten fragments present solely in strains
      CF10 and CF40. The RAPD fragments were cloned, sequenced and used to design two
      SCAR primers. Two primer pairs obtained from SCH3RAPD fragment of CF 40 and 6RAPD
      of CF10 were highly specific and sensitive. CONCLUSIONS: In this study, we
      developed strain-specific multiplex-PCR based on sequence-characterized amplified
      region (SCAR) markers to simultaneously detect both strains in a single PCR.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This new multiplex-PCR provides a valuable
      tool for specific and sensitive identification of CF10 and CF40, and could be
      used in studies on the efficacy and persistence of introduced strains of A.
      pullulans for fire blight control.

PMID- 18070036
TI  - Isolation of new toluene-tolerant marine strains of bacteria and characterization
      of their solvent-tolerance properties.
AB  - AIMS: To isolate and characterize new marine bacteria capable of tolerating high
      concentrations of organic solvents, and to understand the toxic effects of these
      chemicals on marine bacteria. METHODS AND RESULTS: Five marine bacteria able to
      tolerate 0.1% (v/v) toluene were isolated and characterized on the basis of their
      growth and survival rates in the presence of different organic solvents. The
      toluene-tolerant marine bacteria identified in this study could not grow in the
      presence of 0.1% (v/v) of several organic solvents with a log P(ow) higher than
      that of the toluene (which in theory should be less toxic than toluene). The
      mechanisms underlying solvent tolerance were explored. CONCLUSIONS: Isolates of
      four different genera were identified as toluene-tolerant. Toxicity of a second
      phase of an organic solvent toward these isolates could not be predicted on the
      basis of the solvents' log P(ow). SIGNIFICANCE AND IMPACT OF THE STUDY: To
      improve the biodegradation rate of some water-insoluble compounds, double-phase
      bioreactors can be used. This type of bioreactor will require strains able to
      grow in a salt-containing environment and able to tolerate a second phase of an
      organic solvent.

PMID- 18070037
TI  - Evaluation of the spoilage lactic acid bacteria in modified-atmosphere-packaged
      artisan-type cooked ham using culture-dependent and culture-independent
      approaches.
AB  - AIMS: To investigate microbial diversity and population dynamics of spoilage
      sensitive modified-atmosphere-packaged (MAP) artisan-type cooked ham in relation
      to storage temperature. METHODS AND RESULTS: Modified-atmosphere-packaged cooked
      ham samples were stored at different temperatures (4, 7, 12 and 26 degrees C).
      Traditional methods were combined with polymerase chain reaction (PCR)-based
      techniques, i.e. a culture-dependent, repetitive DNA sequence-based method (rep
      PCR) and a culture-independent approach (PCR-denaturing gradient gel
      electrophoresis of 16S rRNA gene fragments; PCR-DGGE). rep-PCR on DNA extracted
      from MRS isolates indicated that Leuconostoc carnosum and Enterococcus faecalis
      prevailed at all temperatures, with the latter becoming more important above 7
      degrees C. PCR-DGGE indicated the additional presence of Carnobacterium divergens
      and Brochothrix thermosphacta at all temperatures. Discriminant analysis related
      variation within the Leuc. carnosum cluster to the storage temperature. High
      performance liquid chromatography revealed that lactic acid was the main
      metabolite because of glucose consumption. CONCLUSIONS: Leuconostoc carnosum, C.
      divergens, E. faecalis and Br. thermosphacta are the main spoilage bacteria of
      artisan-type MAP cooked ham. Their population dynamics are affected by storage
      temperature. SIGNIFICANCE AND IMPACT OF THE STUDY: Temperature can condition the
      development of spoilage in artisan-type MAP cooked ham, acting at both species
      and biotype level.

PMID- 18070038
TI  - Activity and mechanism of the action of zeylasterone against Bacillus subtilis.
AB  - AIMS: To investigate the antimicrobial properties of 6-oxophenolic triterpenoids
      isolated from Maytenus blepharodes against different micro-organisms and the mode
      of action on Bacillus subtilis. METHODS AND RESULTS: The activity of zeylasterone
      and demethylzeylasterone was evaluated by microdilution method. Zeylasterone
      showed a higher activity, being active against Gram-positive bacteria (minimum
      inhibitory concentration 3-20 microg ml(-1)) and Candida albicans (10 microg ml(
      1)). Killing curves revealed a bacteriostatic effect on B. subtilis that was
      dependent on the growth phase and inoculum size. Zeylasterone caused cell
      membrane alterations in B. subtilis, as shown by potassium leakage and formation
      of mesosome-like structures. However, membrane disruption was not revealed by
      either LIVE/DEAD Baclight assay or measurement of intracellular constituent
      efflux. Zeylasterone showed an early effect on N-acetyl-glucosamine and uridine
      incorporation and later on that of thymidine and leucine. CONCLUSIONS: Diverse
      micro-organisms exhibit sensitivities towards compounds studied. The permeability
      changes in the cytoplasmic membrane and nonsimultaneous ceasing of macromolecular
      synthesis suggest that zeylasterone could act on multiple targets on B. subtilis.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The activity showed against B. subtilis as
      a model of spore-forming bacteria would provide valuable information for further
      studies in the development of 6-oxophenolic triterpenoids as antiseptic and
      disinfectant properties.

PMID- 18070039
TI  - Survival and growth of Salmonella Enteritidis PT 30 in almond orchard soils.
AB  - AIMS: To evaluate factors potentially contributing to the long-term persistence
      of Salmonella enterica serovar Enteritidis phage type (PT) 30 in an almond
      orchard. METHODS AND RESULTS: Surface and subsurface soil temperatures, and air
      temperatures in a radiation shelter, were recorded during a 12-month period, and
      were used to identify relevant storage temperatures (20 or 35 degrees C) for
      microcosms of two different soil types (clay and sandy loams) with moisture
      levels near saturation or near field capacity. Salmonella Enteritidis PT 30 was
      inoculated into the microcosms at 6 log CFU g(-1) dry weight. Between 14 and 180
      days of incubation, counts of S. Enteritidis PT 30 decreased rapidly at 35
      degrees C and were significantly different (P < 0.05) from counts at 20 degrees
      C, regardless of the soil type or moisture level. Salmonella was detected by
      enrichment of 10-g samples from all microcosms after 180 days of incubation at 20
      degrees C, but from none of the microcosms held at 35 degrees C. To measure the
      potential for the growth of S. Enteritidis PT 30 in clay loam soil, an aqueous
      extract of almond hulls (containing 1.6% mono and disaccharides) or equivalent
      volume of water was added 7 days after inoculation. Significant (P < 0.05) growth
      of S. Enteritidis PT 30 was observed within 8 or 24 h of adding hull extract, but
      not water, to soil. CONCLUSIONS: Opportunities may exist for S. Enteritidis PT 30
      to survive for an extended time in almond orchard soils and to grow in these
      soils where hull nutrients are released. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Temperature has a significant impact on the long-term survival of S. Enteritidis
      PT 30 in soil, and nutrients leached from almond hulls may result in Salmonella
      growth. These factors should be considered in the design of Good Agricultural
      Practices for almonds.

PMID- 18070040
TI  - Antimycin A-producing nonphytopathogenic Streptomyces turgidiscabies from potato.
AB  - AIM: To detect if substances with mammalian cell toxicity are produced by
      Streptomyces turgidiscabies and Streptomyces scabiei isolated from potato scab
      lesions. METHODS AND RESULTS: In vitro cultures of phytopathogenic and
      nonphytopathogenic strains of S. scabiei and S. turgidiscabies, isolated from
      scab lesions of potato tubers originating from nine different cultivars from
      Finland and Sweden, were tested for toxicity using the rapid spermatozoan
      motility inhibition assay, previously shown useful in the detection of many
      different Streptomyces toxins and antimicrobial compounds. Purified toxins were
      used as reference. Three nonphytopathogenic strains of S. turgidiscabies were
      found to produce antimycin A when cultured on solid medium. CONCLUSIONS: Boar
      sperm-motility-inhibiting substances are produced by strains of S. turgidiscabies
      and S. scabiei. The most powerful inhibitory substance, produced by three
      nonphytopathogenic S. turgidiscabies strains, was identified as antimycin A. The
      phytotoxic compounds thaxtomin A and concanamycin A did not inhibit sperm
      motility even at high doses. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence
      of antimycin A-producing Streptomyces strains, nonpathogenic to potato, was
      unexpected but important, considering the high mammalian toxicity of this
      cytochrome bc-blocking antibiotic.

PMID- 18070041
TI  - Climate change and outbreaks of the geometrids Operophtera brumata and Epirrita
      autumnata in subarctic birch forest: evidence of a recent outbreak range
      expansion.
AB  - 1. Range expansions mediated by recent climate warming have been documented for
      many insect species, including some important forest pests. However, whether
      climate change also influences the eruptive dynamics of forest pest insects, and
      hence the ecological and economical consequences of outbreaks, is largely
      unresolved. 2. Using historical outbreak records covering more than a century, we
      document recent outbreak range expansions of two species of cyclic geometrid
      moth, Operophtera brumata Bkh. (winter moth) and Epirrita autumnata L. (autumnal
      moth), in subarctic birch forest of northern Fennoscandia. The two species differ
      with respect to cold tolerance, and show strikingly different patterns in their
      recent outbreak range expansion. 3. We show that, during the past 15-20 years,
      the less cold-tolerant species O. brumata has experienced a pronounced north
      eastern expansion into areas previously dominated by E. autumnata outbreaks.
      Epirrita autumnata, on the other hand, has expanded the region in which it
      exhibits regular outbreaks into the coldest, most continental areas. Our findings
      support the suggestion that recent climate warming in the region is the most
      parsimonious explanation for the observed patterns. 4. The presence of O. brumata
      outbreaks in regions previously affected solely by E. autumnata outbreaks is
      likely to increase the effective duration of local outbreaks, and hence have
      profound implications for the subarctic birch forest ecosystem.

PMID- 18070042
TI  - Demography of male reproductive queues in cooperatively breeding superb fairy
      wrens Malurus cyaneus.
AB  - 1. Subordinate helpers in cooperative societies may gain both immediate and
      future benefits, including paternity and territorial inheritance. However, if
      such opportunities correlate with rank in the queue, it is unclear why such
      queues should be stable. 2. In cooperatively breeding superb fairy-wrens Malurus
      cyaneus, only males are generally philopatric, and form stable hierarchical
      queues for the dominant position. 3. Male opportunities for reproduction are
      influenced both by their dominance status within the group, and their relatedness
      to the breeding female. For young queuing subordinates, the breeding female is
      typically their mother. Because of incest avoidance, reproduction is possible
      only through extra-group mating, even if the dominant position is achieved while
      the mother is still on the territory. If the mother dies while the helper is
      still a subordinate, he can seek matings both outside the group, and with the
      unrelated replacement female within the group. Finally, males can achieve the
      dominant position and pair with an unrelated female by inheritance, dispersal to
      a neighbouring vacancy, or by forming a liaison with an immigrant subordinate
      female that causes fission of the natal territory. 4. On average males spent more
      time living with unrelated females than with their mother. Subordinate males
      gained no survival advantages when living with their mother rather than an
      unrelated female, contrary to the prediction that parents facilitate the survival
      of their offspring. 5. Dominants and subordinates also had similar survival.
      Mortality accelerated over time, probably because older males invest more in
      extra-group courtship display. 6. Fairy-wren queues are likely to be stable
      because older birds are superior, and because extra-pair mating provides direct
      benefits to subordinates.

PMID- 18070043
TI  - Self-rated health and classical risk factors for coronary heart disease predict
      development of erectile dysfunction 25 years later.
AB  - AIM: To investigate the impact of classical coronary heart disease (CHD) risk
      factors on the development of future erectile dysfunction (ED). METHODS AND
      RESULTS: A total of 830 randomly selected subjects were included. Baseline CHD
      risk factors were evaluated in relation to ED (evaluated by the International
      Index of Erectile Function-5 questionnaire) 25 years later. At follow-up, 499 men
      (60%) had some degree of ED. In age-adjusted logistic regression analysis, self
      rated health [odds ratio (OR) 1.59, 95% confidence interval (CI): 1.09-2.31],
      family history of CHD (OR 1.75, CI: 1.17-2.61), fasting blood glucose (OR 1.52,
      CI: 1.14-2.02), triglycerides (OR 1.25, CI: 1.01-1.54), systolic blood pressure
      (SBP) (OR 1.19, CI: 1.04-1.35), body mass index (OR 1.08, CI: 1.03-1.13) and
      serum glutamyl transferase (GT) (OR 1.81, CI: 1.23-2.68), predicted ED.
      Independent predictors were higher age, low self-rated health, higher blood
      glucose, higher GT and a family history of CHD. Higher SBP was borderline
      significantly independent (p=0.05). Furthermore, baseline age-adjusted Framingham
      risk score for CHD, also predicted future ED (OR 1.20, CI: 1.03-1.38).
      CONCLUSIONS: Our study supports and expands previous findings that ED and CHD
      share many risk factors, further underscoring the close link between ED and CHD.
      Men presenting with ED should be evaluated for the presence of other CHD risk
      factors.

PMID- 18070044
TI  - Management of heart failure in elderly people.
AB  - AIMS: To review currently available knowledge on presentation, clinical features
      and management of heart failure (HF) in elderly people. METHODS: To review
      currently available evidence, we performed a thorough search of several evidence
      based sources of information, including Cochrane Database of Systematic Reviews,
      Clinical Evidence, Evidence-based guidelines from National Guidelines
      Clearinghouse and a comprehensive MEDLINE search with the MeSH terms: 'heart
      failure', 'elderly' and 'management'. RESULTS: A number of features of ageing may
      predispose elderly people to HF, and may impair the ability to respond to
      injuries. Another hallmark of elderly patients is the increasing prevalence of
      multiple coexisting chronic conditions and geriatric syndromes that may
      complicate the clinical presentation and evolution of HF. Although diagnosis may
      be challenging, because atypical symptoms and presentations are common, and
      comorbid conditions may mimic or complicate the clinical picture, diagnostic
      criteria do not change in elderly people. Drug treatment is not significantly
      different from that recommended in younger patients, and largely remains empiric,
      because clinical trials have generally excluded elderly people and patients with
      comorbid conditions. Disease management programmes may have the potential to
      reduce morbidity and mortality for patients with HF. CONCLUSIONS: Heart failure
      is the commonest reason for hospitalisation and readmission among older adults.
      HF shows peculiar features in elderly people, and is usually complicated by
      comorbidities, presenting a significant financial burden worldwide, nevertheless
      elderly people have been generally excluded from clinical trials, and thus
      management largely remains empiric and based on evidence from younger age groups.

PMID- 18070045
TI  - The efficacy of oxycodone for management of acute pain episodes in chronic neck
      pain patients.
AB  - OBJECTIVE: Most treatments of acute pain associated with non-malignant chronic
      pains are not satisfactory. The aim of this study is to evaluate the efficacy and
      side effects of oxycondone controlled release (Oxy-CR) in managing chronic neck
      pain with acute pain episodes. DESIGN: Randomised, double-blind, stand controlled
      study. A total of 116 patients were evenly divided into an oxycodone group (Oxy
      CR, 5-10 mg and q12 h/day) and a placebo group (placebo, q12 h/day). Patients
      were assessed for the frequency of pain flares, visual analgesia score (VAS),
      quality of life (QOL), quality of sleep (QOS) and adverse effects before the
      treatment and on days 1, 3, 7, 14, 21 and 28 after the treatment. Withdrawal
      symptoms were monitored during the study, also on the completion of the entire
      study. The SF-36 was administered at the beginning and the end of the study for
      each patient. RESULTS: Compared with the baselines of Oxy-CR and the placebo
      groups, the frequency of pain episodes and VAS were decreased significantly
      starting on day 3 of administration of Oxy-CR (p<0.05). Improvements in QOL and
      QOS were significant on day 3 after treatment with Oxy-CR (p<0.05). The patients
      who were treated with Oxy-CR reported significantly higher side effects than the
      patients in the placebo group (p<0.05). However, these side effects started to
      diminish after day 7 of the treatment. Withdrawal symptoms did not emerge in this
      study. Most domains of SF-36 were improved in the treated patients at the end of
      study (p<0.05). CONCLUSION: Oxycondone controlled release could be an important
      optional drug for the management of refractory and frequent acute episodes of
      chronic neck pain in patients who failed to respond to non-opioid conservative
      treatment.

PMID- 18070046
TI  - Fluorescence microscopy and flow cytometry in measuring activated caspases in
      human spermatozoa.
AB  - Staining of spermatozoa with the fluorescein-Val-Ala-Asp-fluoromethylketone has
      already been performed on ejaculated sperm samples, using fluorescence microscopy
      (FM) or flow cytometry (FCM) in order to score activated caspases. This assay may
      help in assessing apoptosis and its role in male fertility. The present study
      compares the above two techniques in order to adopt the most accurate method for
      detection in human frozen-thawed testicular, epididymal and ejaculated
      spermatozoa. The analyses were carried out on frozen/thawed testicular (n = 14),
      epididymal (n = 8) and ejaculated (n = 10) sperm samples. Activated caspases were
      detected in living spermatozoa using fluorescein-labelled inhibitors of poly
      caspases (FLICA). For the measurements by FM, the same-observer and different
      observer reliability were assessed in testicular and epididymal sperm samples.
      The inter-method (FM and FCM) reliability was assessed both in epididymal and
      ejaculated sperm samples. The reliability was evaluated by intraclass correlation
      coefficient (ICC) and the differences between paired measurements from the same
      sample were tested by Wilcoxon test for matched pairs. For the same-observer and
      the different-observer data, the ICC were 0.980 and 0.986. In testicular
      suspensions, the presence of different types of germinal and somatic cells
      hampers the differentiation of stained spermatozoa by FCM. For the inter-method
      reliability, the ICC was 0.903. A lower proportion of the viable spermatozoa
      stained with FLICA was observed by using FM (-6.60 +/- 7.38 %, mean +/- SD; p =
      0.003) compared with FCM. To measure the proportion of spermatozoa with activated
      caspases by this test, FM is a highly accurate and reliable method whatever the
      sperm origin (ejaculate, epididymis, and testis). FCM cannot be used for
      testicular samples but seems to be more appropriate for analysis of epididymal
      and ejaculated sperm samples. The systematic lower proportion by FM in measuring
      the proportion of stained viable spermatozoa with FLICA involves that only the
      data measured by the same method (FM or FCM) may be compared.

PMID- 18070047
TI  - Quantification of seminal germ cells in azoospermia: correlations with testicular
      histology and TESE outcome.
AB  - In the treatment of male infertility by intra-cytoplasmic injection of
      spermatozoa (ICSI) extracted from testicular tissue (TESE), the high incidence of
      negative TESE outcome calls for non-invasive prognostic methods. Literature
      suggests that seminal haploid germ cell detection could be one. For this purpose,
      a multi-parametric stringent flow cytometric method was applied to 50 TESE
      patients for the quantification of ejaculated germ cells. Cells from 50
      ejaculates were identified and quantified as spermatozoa (HC, highly condensed),
      round spermatids (1N), primary spermatocytes (SPC) (4N) or diploid cells (2N,
      including somatic and non-testicular cells) by their DNA and mitochondria
      staining and laser scatter characteristics, and compared with testicular biopsy
      histology and TESE outcome. Whereas 96% of patients displayed a diploid peak in
      the distribution histograms, the HC, 1N and 4N peaks were absent from the
      majority of samples. In 13 ejaculates, either a HC or 1N or 4N peak, or a
      combination of these, was discernible. Although seminal germ cell numbers bore no
      overall association with elongated spermatids (ES) in histology or spermatozoa
      retrieval in TESE outcome, 4N cells per ejaculate were correlated with the
      percentage of tubule sections showing SPC as the most advanced germ cells. The
      incidence of HC peaks was higher in patients showing some ES in histology or
      sperm retrieval than in the sperm-negative groups. In groups with suspected
      obstruction showing nearly full spermatogenesis and maximal sperm retrieval,
      there was no incidence of a HC peak. Germ cell peaks were associated with germ
      cell degeneration noted in testicular histology. In conclusion, seminal germ
      cells cannot provide good prognosis for TESE, although their presence could
      indicate the spermatogenic activity in the testis.

PMID- 18070048
TI  - Phthalates: metabolism and exposure.
AB  - In human metabolism studies we found that after oral application of di(2
      ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP) and di(2-propylheptyl)
      phthalate (DPHP), at least 74, 44 and 34%, respectively, are excreted via urine.
      In contrast to the short chain phthalates, their oxidized products, not the
      simple monoesters, were found to be the main metabolites. Based on urinary
      phthalate metabolite concentrations we estimated in 102 German subjects between 6
      and 80 years of age median daily intakes (microg/kg/day) of 2.7 for DEHP, 2.1 for
      di-n-butyl phthalate, 1.5 for diisobutyl phthalate, 0.6 for DiNP, and 0.3 for
      butylbenzyl phthalate. In general, children have higher exposures compared to
      adults and seem to have a more effective oxidative metabolism of phthalates. For
      individual phthalates tolerable daily intake (TDI) values have been deduced.
      However, in rats some phthalates have been shown to act as endocrine disrupters
      via a common mechanism of action in a dose-additive manner. Therefore, the
      concept of a cumulative TDI value may be more appropriate for the consideration
      of the overall exposure and the potential human health risks resulting from
      everyday and simultaneous exposure to several phthalates.

PMID- 18070049
TI  - Electromyographic study of ejaculatory mechanism.
AB  - Cavernosus muscle (CM), seminal vesicle (SV) and vasal ampullary (VA)
      contractions at ejaculation are said to be reflex mechanisms (ejaculatory
      reflex), which have been scarcely dealt with in the literature. We investigated
      the hypothesis that contraction of the CMs, SVs and VA at ejaculation is a reflex
      action. The electromyographic (EMG) activity of CM, SV and VA during ejaculation
      was recorded in 28 healthy men. The test was repeated after separate
      anaesthetization of the glans penis (GP), CMs, SVs, and VA in the pre-ejaculatory
      period. Latent ejaculatory time (LET) was calculated. CMs showed no EMG activity
      until rigid erection phase was reached. SVs and VA exhibited resting EMG activity
      which increased gradually with different stages of erection. At ejaculation, CMs,
      SVs and VA showed two to four intermittent contractions. The mean LET was 1.3 +/-
      0.2 sec. GP anaesthetization led to the disappearance of CM, SV and VA EMG
      activity at ejaculation, while bland gel did not affect EMG activity. CMs, SVs
      and VA when anaesthetized in the pre-ejaculatory period exhibited no EMG activity
      at ejaculation, while saline did not affect EMG activity. Increased EMG activity
      of CM, SV and VA apparently denotes increase in their contractile activity. CM,
      SV and VA contraction on GP stimulation and ejaculation are assumed to be reflex
      actions and are mediated through the 'glans-cavernosovesicular reflex' (GCVR)
      which presumably represents the ejaculatory reflex. Changes in LET or evoked
      response would indicate a defect in the reflex pathway. The GCVR might act as an
      investigative tool in diagnosing erectile dysfunction, provided further studies
      are performed in this respect.

PMID- 18070050
TI  - p53 and Ki-67 expression in renal cell carcinomas of pregnant women and their
      correlation with prognosis: a pilot study.
AB  - In the present study, we reported two cases of renal cell carcinoma (RCC)
      diagnosed in pregnant women (Pt) that were submitted to radical nephrectomy, in
      both cases within the fourth month. The patients, after 13 and 3 years,
      respectively, did not show evidence of recurrent disease. We performed an
      immunohistochemical study on RCC specimens in comparison to seven age-matched
      controls (Cl). The panel of antibodies included Ki-67, p53, bcl-2, ER, PgR, PCNA,
      and IGF-1. We describe a difference in the expression of p53 and Ki-67.
      Specifically, p53 was highly expressed in RCC of both Pt but scarcely present or
      absent in Cl; by contrast, Ki-67 was hardly expressed or negative in RCC of both
      Pt, being commonly positive in Cl. These results may correlate with a good
      outcome of the disease in Pt. Although the limited number of cases did not permit
      any statistical evaluation, we postulate that these differences have not to be
      underestimated since they may disclose a correlation between pregnancy and
      biological behavior of tumoral disease. Further study may (dis)prove this
      hypothesis.

PMID- 18070051
TI  - Effect of genipin on the biliary excretion of cholephilic compounds in rats.
AB  - AIM: Genipin, a metabolite of geniposide, is reported to stimulate the insertion
      of multidrug resistance protein 2 (Mrp2) in the bile canalicular membrane, and to
      cause choleresis by increasing the biliary excretion of glutathione, which has
      been considered to be a substrate of Mrp2. In the present study, the effect of
      colchicine on the choleretic effect of genipin was investigated. The effect of
      genipin on the biliary excretion of the substrates of bile salt export pump and
      Mrp2 was also studied. METHODS: After bile duct cannulation into rats, genipin
      was administered at the rate of 0.2 mumol/min/100 g, and the effect of colchicine
      pretreatment (0.2 mg/100 g) was examined. Metabolites of genipin in the bile were
      examined by a thin layer chromatography. Taurocholate (TC), sulfobromophthalein
      (BSP), and pravastatin were infused at the rate of 1.0, 0.2 and 0.3 mumol/min/100
      g, respectively, and the effect of genipin co-administration was examined.
      RESULTS: Genipin increased bile flow and the biliary glutathione excretion, and
      those increases were not inhibited by colchicine. The biliary excretion of
      genipin glucuronide was less than 10% of the genipin excreted into bile. The
      biliary excretion of TC, BSP, and pravastatin was unchanged by genipin co
      administration. CONCLUSION: It was indicated that colchicine-sensitive vesicular
      transport has no role on the genipin-induced insertion of Mrp2 to the canalicular
      membrane. Choleresis of genipin is considered to be mainly due to the increased
      biliary glutathione excretion by genipin, not by the biliary excretion of
      glucuronide. TC had no effect on the biliary glutathione excretion.

PMID- 18070052
TI  - Early emergence of entecavir-resistant hepatitis B virus in a patient with
      hepatitis B virus/human immunodeficiency virus coinfection.
AB  - The efficacy of entecavir for patients with hepatitis B virus/human
      immunodeficiency virus coinfection has not been fully elucidated. Here we
      examined a patient coinfected with both viruses in whom entecavir-resistant
      hepatitis B virus appeared. The 60-year-old Japanese male with the coinfection
      received antiretroviral therapy including lamivudine. The therapy initially
      suppressed replication of both viruses, followed by reactivation of the hepatitis
      B virus alone by 2 years of therapy. He subsequently received entecavir therapy
      in addition to the antiretroviral regimen. After entecavir administration, the
      hepatitis B virus DNA level was slightly reduced, but then increased after 6
      months of entecavir therapy. In the sequencing analysis of hepatitis B virus, no
      drug resistance-associated amino acid substitutions were observed in the reverse
      transcriptase (rt) domain before antiretroviral therapy. The lamivudine-resistant
      amino acid substitutions at rt173, rt180 and rt204 were detected before entecavir
      administration, and further the entecavir-resistant rt202 substitution was
      observed after 6 months of entecavir therapy. The full-length hepatitis B
      sequences showed that the viral strain derived from the patient belonged to
      genotype H. In summary, this report describes a patient with hepatitis B
      virus/human immunodeficiency virus coinfection who received entecavir therapy in
      addition to an antiretroviral regimen and showed the early emergence of entecavir
      resistance hepatitis B virus. In entecavir therapy for patients infected with
      both viruses, great care should be taken with respect to the emergence of
      entecavir-resistant hepatitis B virus, especially in patients with pre-existing
      lamivudine-resistant virus.

PMID- 18070053
TI  - Molecular mechanisms of portal vein tolerance.
AB  - The liver has been considered as a tolerogenic organ in the sense that favors the
      induction of peripheral tolerance. The administration of antigens (Ags) via the
      portal vein causes tolerance, which is termed portal vein tolerance and can
      explain the occurrence of tolerogenic responses in the liver. Here we discuss the
      fundamental mechanisms accounting for portal vein tolerance. Antigen-presenting
      cells (APCs) in the liver, especially dendritic cells and sinusoidal endothelial
      cells, have limited the ability to produce pro-inflammatory cytokines upon
      stimulation with endotoxin, an effect that could be due to the continuous
      exposure to bacterial Ags derived from intestinal microflora. Ag presentation by
      liver APCs results in T cell tolerance through clonal deletion and selection of
      regulatory T cells. Thus, APCs with immunosuppressive functions are associated
      with the achievement of portal vein tolerance via the induction of clonal
      deletion and generation of regulatory T cells.

PMID- 18070054
TI  - Microencapsule technique protects hepatocytes from cryoinjury.
AB  - AIM: Hepatocyte transplantation is a potential alternative to whole organ liver
      transplantation. To realize this procedure, a hepatocyte bank system capable of
      supplying large numbers of hepatocytes must be established. We previously
      reported an easy method for cryopreserving hepatocytes using a microencapsulation
      technique. Here, we investigated how cryoinjury to microencapsulated hepatocytes
      could be avoided during cryopreservation. METHODS: Hepatocytes from Sprague
      Dawley rats were harvested in situ using a two-step ethylenediaminetetraacetic
      acid (EDTA)/collagenase digestion protocol. The cells were microencapsulated
      using alginate-poly L-lysine. The microencapsulated hepatocytes were put into
      vials and immediately immersed in liquid nitrogen. The growth of ice crystals in
      the vials containing the microencapsulated hepatocytes was observed using
      cryomicroscopy. The microencapsulated hepatocytes were sectioned for
      ultrastructural examination to investigate their intracellular conditions.
      Finally, total RNA was isolated from the cryopreserved microencapsulated
      hepatocytes and analyzed for hepatocyte nuclear factor (HNF) using reverse
      transcriptase polymerase chain reaction (RT-PCR) analysis. RESULTS:
      Cryomicroscopy showed that the alginate microencapsulation technique protected
      the hepatocytes from physical damage caused by the growth of extracellular ice
      crystals. Ultrastructural examination revealed that the intracellular environment
      of the microencapsulated hepatocytes was maintained. The RT-PCR analysis
      additionally suggested that the alginate gel also maintained the HNF level.
      CONCLUSION: Our microencapsulation technique protects hepatocytes from
      cryoinjury. This novel technique could be utilized by hepatocyte banks.

PMID- 18070055
TI  - "A transcript of actual life": headache in the novels of Jane Austen.
AB  - References to headache in the novels of Jane Austen have been examined. Nine
      characters, all female, suffer headache at one time or another, often in
      association with emotionally stressful situations. As an authorial device,
      headache may have served Jane Austen as a culturally sanctioned form of bodily
      expression.

PMID- 18070056
TI  - Clomiphene citrate for treatment refractory chronic cluster headache.
AB  - A treatment refractory chronic cluster headache patient is presented who became
      cluster-free on clomiphene citrate. The author has previously reported a SUNCT
      patient responding to clomiphene citrate. Hypothalamic hormonal modulation
      therapy with clomiphene citrate may become a new preventive choice for trigeminal
      autonomic cephalalgias. The possible mechanism of action of clomiphene citrate
      for cluster headache prevention will be discussed.

PMID- 18070057
TI  - Direct cost burden among insured US employees with migraine.
AB  - OBJECTIVE: To provide a current estimate of the national direct health-care cost
      burden of illness associated with migraine among a US insured population.
      BACKGROUND: Individuals with migraine use health-care resources more than those
      without migraine, incurring substantial costs to US employers. METHODS: The
      Thomson Medstat's Commercial Claims and Encounters 2004 database was utilized for
      this study. Only paid claims were analyzed. The migraine cohort had a primary
      migraine diagnosis and/or a migraine-specific abortive drug prescription during
      2004. A matched control cohort with no evidence of migraine was generated using
      propensity score techniques. Demographic characteristics and overall
      comorbidities were similar between cohorts. A second-stage regression controlled
      for any remaining significant intergroup differences. The burden of illness of
      migraine was defined as the difference in average total health-care expenditures
      per person between cohorts. The national burden of illness was defined as the
      average expenditure for migraine of national population estimates of privately
      insured individuals, and was estimated by projecting the migraine prevalence rate
      and average expenditure using Medical Expenditure Panel Survey population
      estimates. RESULTS: Patients with migraine (n=215,209) had significantly higher
      average health-care expenditures compared with matched controls ($7007 vs $4436
      per person per year; difference of $2571; P<.001). Migraine-associated national
      expenditure estimates: outpatient care, $5.21 billion; prescriptions, $4.61
      billion; inpatient care, $0.73 billion; and emergency department care, $0.52
      billion. CONCLUSIONS: The direct costs associated with patients with migraine
      were found to be $2571 per person per year higher than in matched nonmigraine
      controls. The projected national burden of migraine of $11.07 billion is
      substantially higher than previous estimates.

PMID- 18070058
TI  - Heart rate recovery in migraine and tension-type headache.
AB  - OBJECTIVE: There are reports proposing that migraine and tension-type headache
      (TTH) may affect the autonomic nervous system (ANS). Abnormalities in both
      sympathetic and parasympathetic nervous system have been suggested in
      migraineurs. However, in TTH, reports on the ANS function are limited and only
      associated with sympathetic system. Techniques for evaluating parasympathetic
      activity are more limited when compared with sympathetic function. Hence, the aim
      of the study was to measure heart rate recovery (HRR), an index of vagal
      activity, in migraine, TTH, and control subjects. METHODS: Forty-seven episodic
      migraine, 10 episodic TTH, 11 chronic TTH, and 25 control subjects underwent
      exercise tolerance test according to modified Bruce protocol, and HRR at 1 minute
      and 3 minutes (HRR1 and HRR3) were calculated. RESULTS: The HRR 1 and 3 were
      found to be similar in 3 groups of subjects. However, resting heart rate of
      migraine and chronic TTH were found to be higher than episodic TTH, but not
      different from the control group. CONCLUSION: These results suggest that
      parasympathetic function has not been affected in migraine and TTH patients.
      However, sympathetic tonus, which is evaluated by resting heart rate, is higher
      in migraine and chronic TTH than in episodic TTH.

PMID- 18070059
TI  - Comorbidity of migraine and psychiatric disorders--a national population-based
      study.
AB  - BACKGROUND: Migraine is common, with an estimated lifetime prevalence of 7-17%.
      Population-based studies have reported an association between various psychiatric
      conditions and migraine. This is a population-based study exploring the
      association between migraine and psychiatric disorders in a large cohort and
      assessing various health-related outcomes. OBJECTIVE: (1) Determine the
      prevalence of various psychiatric conditions in association with migraine; (2)
      describe the patterns of association of these comorbidities with a variety of
      health-related outcomes. METHODS: Data from the 2002 Canadian Community Health
      Survey were used. This is a national health survey which included administration
      of the World Mental Health Composite International Diagnostic Interview to a
      sample of 36,984 subjects. Health-related outcomes included 2-week disability,
      restriction of activities, quality-of-life, and mental health care utilization.
      RESULTS: The prevalence of physician-diagnosed migraine (n=36,984) was 15.2% for
      females and 6.1% for males. Migraine was most common in those between ages 25 and
      44 years and in those of lower income. Migraine was associated with major
      depressive disorder, bipolar disorder, panic disorder, and social phobia, all
      occurring more than twice as often in those with migraines compared with those
      without. Migraine was not associated with drug, alcohol, or substance dependence.
      The higher prevalence of psychiatric disorders in migraineurs was not related to
      sociodemographic variables. Psychiatric disorders were less common in those over
      65 years, in those who were in a relationship, and in those of higher income
      whether migraine was present or not. Health-related outcomes were worst in those
      with both migraines and a psychiatric disorder and intermediate in those with
      either condition alone. CONCLUSION: Migraine is associated with major depressive
      disorder, bipolar disorder, panic disorder, and social phobia. Migraine in
      association with various mental health disorders results in poorer health-related
      outcomes compared with migraine or a psychiatric condition alone. Understanding
      the psychiatric correlates of migraine is important in order to adequately manage
      this patient population and to guide public health policies regarding health
      services utilization and health-care costs.

PMID- 18070060
TI  - Drug induced intracranial hypertension associated with sulphasalazine treatment.
AB  - A 25-year-old female patient developed headache and papilledema under
      sulphasalazine treatment for ulcerative colitis. The patient met the
      International Headache Society's criteria for idiopathic intracranial
      hypertension. Sulphasalazine was discontinued and the patient was given
      azathioprine for ulcerative colitis and acetazolamide for intracranial
      hypertension. Three weeks later, her examination was normal and lumbar puncture
      revealed an opening pressure of 180-mm H(2)O. Sulphasalazine is a product of 5
      aminosalicylate (5 ASA) and there seems to be a relationship between the
      administration of sulphasalazine and the onset of intracranial hypertension
      symptoms. Early diagnosis of intracranial hypertension is important in patients
      with ulcerative colitis receiving 5 ASA treatment to prevent visual
      complications.

PMID- 18070061
TI  - Patulous eustachian tube in spontaneous intracranial hypotension syndrome.

PMID- 18070062
TI  - Factor VIII products and inhibitor development: concepts for revision of European
      regulatory guidelines.

PMID- 18070063
TI  - The impact on parents of developments in the care of children with bleeding
      disorders.
AB  - This research considered the impact on parents of children with bleeding
      disorders of the increased use of home-based treatment and greater parental
      responsibility for management of the condition. Although they have undoubted
      advantages, these changes also present parents with new challenges. Some found
      administration of the treatment difficult, and decisions about treatment and the
      everyday management of the condition can also prove problematic. Services should
      be aware of these issues and help parents access appropriate support.

PMID- 18070064
TI  - Gastrointestinal bleeding due to angiodysplasia in patients with type 1 von
      Willebrand disease: report on association and management.

PMID- 18070065
TI  - Evaluation of rFVIIa (NovoSeven) in Glanzmann patients with thromboelastogram.
AB  - Glanzmann thrombasthenia (GT) is a rare platelet function disorder characterized
      by a defect in fibrinogen binding to platelet membrane glycoprotein (GP)
      IIb/IIIa. Recombinant FVIIa (rFVIIa) is a haemostatic agent approved for the
      treatment of haemophilia patients with inhibitors, patients with acquired
      haemophilia and in EU also for treatment of factor VII (FVII)-deficient patients
      and GT patients with antibodies to GPIIb-IIIa. The present study was conducted to
      evaluate the use of the whole blood test system, rotational thrombelastometry
      (ROTEM), in measuring the overall haemostasis potential of rFVIIa in 28 GT
      patients treated with rFVIIa. The correlation of administered rFVIIa and time to
      start fibrin formation and clot dynamic/stability was assessed and correlation to
      the clinical response was elucidated. Assessments were performed on predose blood
      samples spiked with four different concentrations of rFVIIa and whole blood
      samples taken at 10 and 120 min following dosing. ROTEM parameters clotting time
      (CT), clot formation time (CFT) and maximum clot firmness (MCF) were measured.
      Both ex vivo and in vivo data showed beneficial effects on CT in the presence of
      rFVIIa, but no effect of added rFVIIa was seen on CFT and MCF. In conclusion, the
      use of thrombelastography at least in the modified form of ROTEM seems to be of
      limited use in predicting an adequate dose of rFVIIa in GT patients. A good
      clinical haemostatic response was recorded in spite of the limited changes in the
      ROTEM pattern supporting the conclusion that ROTEM should not be the method of
      choice for monitoring rFVIIa therapy in Glanzmann patients.

PMID- 18070066
TI  - Protein glycation and methylglyoxal metabolism in yeast: finding peptide needles
      in protein haystacks.
AB  - Metabolism, the set of all chemical transformations inside a living cell,
      comprises nonenzymatic processes that generate toxic products such as reactive
      oxygen species and 2-oxoaldehydes. Methylglyoxal, a highly reactive 2-oxoaldehyde
      by-product of glycolysis, is able to react irreversibly and nonenzymatically with
      proteins, forming methylglyoxal advanced glycation end-products, which alter
      protein structure, stability and function. Therefore, protein glycation may
      influence cell metabolism and its physiology in a way beyond what can be
      predicted based on the implicit codification used in systems biology. Genome-wide
      approaches and transcriptomics, two mainstays of systems biology, are powerless
      to tackle the problems caused by nonenzymatic reactions that are part of cell
      metabolism and biochemistry. The effects of methylglyoxal-derived protein
      glycation and the cell's response to this unspecific posttranslational
      modification were investigated in Saccharomyces cerevisiae as a model organism.
      Specific protein glycation phenotypes were identified using yeast null-mutants
      for methylglyoxal catabolism and the existence of specific protein glycation
      targets by peptide mass fingerprint was discovered. Enolase, the major target,
      endures a glycation-dependent activity loss caused by dissociation of the active
      dimer upon glycation at a specific arginine residue, identified using the hidden
      information of peptide mass fingerprint. Once glycation occurs, a cellular
      response involving heat shock proteins from the refolding chaperone pathway is
      elicited and Hsp26p is activated by glycation.

PMID- 18070067
TI  - Sigma factors in Pseudomonas aeruginosa.
AB  - In Pseudomonas aeruginosa, as in most bacterial species, the expression of genes
      is tightly controlled by a repertoire of transcriptional regulators, particularly
      the so-called sigma (sigma) factors. The basic understanding of these proteins in
      bacteria has initially been described in Escherichia coli where seven sigma
      factors are involved in core RNA polymerase interactions and promoter
      recognition. Now, 7 years have passed since the completion of the first genome
      sequence of the opportunistic pathogen P. aeruginosa. Information from the genome
      of P. aeruginosa PAO1 identified 550 transcriptional regulators and 24 putative
      sigma factors. Of the 24 sigma, 19 were of extracytoplasmic function (ECF). Here,
      basic knowledge of sigma and ECF proteins was reviewed with particular emphasis
      on their role in P. aeruginosa global gene regulation. Summarized data are
      obtained from in silico analysis of P. aeruginosasigma and ECF including rpoD
      (sigma(70)), RpoH (sigma(32)), RpoF (FliA or sigma(28)), RpoS (sigma(S) or
      sigma(38)), RpoN (NtrA, sigma(54) or sigma(N)), ECF including AlgU (RpoE or
      sigma(22)), PvdS, SigX and a collection of uncharacterized sigma ECF, some of
      which are implicated in iron transport. Coupled to systems biology,
      identification and functional genomics analysis of P. aeruginosasigma and ECF are
      expected to provide new means to prevent infection, new targets for antimicrobial
      therapy, as well as new insights into the infection process.

PMID- 18070068
TI  - Structural variation in the glycan strands of bacterial peptidoglycan.
AB  - The normal, unmodified glycan strands of bacterial peptidoglycan consist of
      alternating residues of beta-1,4-linked N-acetylmuramic acid and N
      acetylglucosamine. In many species the glycan strands become modified after their
      insertion into the cell wall. This review describes the structure of secondary
      modifications and of attachment sites of surface polymers in the glycan strands
      of peptidoglycan. It also provides an overview of the occurrence of these
      modifications in various bacterial species. Recently, enzymes responsible for the
      N-deacetylation, N-glycolylation and O-acetylation of the glycan strands were
      identified. The presence of these modifications affects the hydrolysis of
      peptidoglycan and its enlargement during cell growth. Glycan strands are
      frequently deacetylated and/or O-acetylated in pathogenic species. These
      alterations affect the recognition of bacteria by host factors, and contribute to
      the resistance of bacteria to host defence factors such as lysozyme.

PMID- 18070069
TI  - TRAIL expression is induced in both osteoblasts containing intracellular
      Staphylococcus aureus and uninfected osteoblasts in infected cultures.
AB  - Staphylococcus aureus is the principal etiological agent of osteomyelitis (bone
      infection), which is characterized by a progressive inflammatory response
      resulting in extensive damage to bone tissue. Recent studies have demonstrated
      the ability of S. aureus to invade and persist inside osteoblasts (bone matrix
      forming cells) and other eukaryotic cells. The presence of intracellular S.
      aureus in bone tissue may be relevant to the pathology of osteomyelitis, a
      disease often refractory to antibiotic treatment and subject to recurrence months
      and even years after apparently successful therapy. The present study examined
      the production of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      following S. aureus infection, and whether expression of the molecule was induced
      by those osteoblasts containing intracellular S. aureus. Results from this study
      suggest that osteoblasts containing intracellular S. aureus induce TRAIL
      expression in uninfected osteoblasts present in infected cultures.

PMID- 18070070
TI  - Efflux system overexpression and decreased OprD contribute to the carbapenem
      heterogeneity in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa strains exhibiting a heterogeneous mode of growth against
      carbapenems have been described recently. This study investigated the underlying
      molecular mechanisms in four genetically unrelated P. aeruginosa clinical
      isolates that were previously characterized by population analyses as
      heterogeneously resistant against carbapenems. Mutant subpopulations of all four
      isolates had at least fourfold higher minimum inhibitory concentrations than
      those of native cells for imipenem and meropenem. The heterogeneous
      subpopulations, when compared with the respective native ones, had significantly
      increased transcription levels of the mexB and mexY genes (P<0.05), whereas
      transcription levels of the mexE gene remained unchanged. They also exhibited
      significantly decreased expression of the oprD gene (P<0.05) and decreased
      intensity of the protein band of the porin OprD. Upregulation of efflux systems,
      in part, and the decrease of OprD contribute to the heterogeneous growth against
      carbapenems in our P. aeruginosa clinical isolates.

PMID- 18070071
TI  - Ramularia collo-cygni: the biology of an emerging pathogen of barley.
AB  - Ramularia collo-cygni is now recognized as an important pathogen of barley in
      Northern Europe and New Zealand. It induces necrotic spotting and premature leaf
      senescence, leading to loss of green leaf area in crops, and can result in
      substantial yield losses. The fungus produces a number of anthraquinone toxins
      called rubellins, which act as host nonspecific toxins with photodynamic
      activity. These toxins induce lipid peroxidation and are possibly the cause of
      the chlorosis and necrosis observed in leaves infected with R. collo-cygni. The
      fact that the fungus can remain latent in barley plants until flowering, coupled
      with its very slow growth in vitro, makes it difficult to detect in crops. As a
      result, the epidemiology of this pathogen remains poorly understood. However, the
      recent development of rapid and reliable PCR methods for specific detection of R.
      collo-cygni offers the prospect of increased understanding of its epidemiology
      and improved disease control.

PMID- 18070073
TI  - Bacteriocins from plant pathogenic bacteria.
AB  - Many bacteria produce antimicrobial substances such as nonribosomally synthesized
      antibiotics and ribosomally synthesized proteinaceous compounds referred to as
      bacteriocins. Secretion of antimicrobials is generally thought to contribute to
      the competitiveness of the producing organism, but there are indications that
      these compounds in some cases may have regulatory roles too. Bacteriocins most
      often act on closely related species only and are thus of interest for
      application as targeted narrow-spectrum antimicrobials with few side effects.
      Although the application of bacteriocins in plant disease control is an
      attractive option, very little is known about the occurrence and roles of these
      compounds in plant pathogenic bacteria and their natural competitors occurring in
      the same biotopes. This study presents an overview of current knowledge of
      bacteriocins from plant pathogenic bacteria.

PMID- 18070072
TI  - Diversity of nifH gene pools in the rhizosphere of two cultivars of sorghum
      (Sorghum bicolor) treated with contrasting levels of nitrogen fertilizer.
AB  - The diversity of nitrogen-fixing bacteria was assessed in the rhizospheres of two
      cultivars of sorghum (IS 5322-C and IPA 1011) sown in Cerrado soil amended with
      two levels of nitrogen fertilizer (12 and 120 kg ha(-1)). The nifH gene was
      amplified directly from DNA extracted from the rhizospheres, and the PCR products
      cloned and sequenced. Four clone libraries were generated from the nifH fragments
      and 245 sequences were obtained. Most of the clones (57%) were closely related to
      nifH genes of uncultured bacteria. NifH clones affiliated with Azohydromonas
      spp., Ideonella sp., Rhizobium etli and Bradyrhizobium sp. were found in all
      libraries. Sequences affiliated with Delftia tsuruhatensis were found in the
      rhizosphere of both cultivars sown with high levels of nitrogen, while clones
      affiliated with Methylocystis sp. were detected only in plants sown under low
      levels of nitrogen. Moreover, clones affiliated with Paenibacillus durus could be
      found in libraries from the cultivar IS 5322-C sown either in high or low amounts
      of fertilizer. This study showed that the amount of nitrogen used for
      fertilization is the overriding determinative factor that influenced the nitrogen
      fixing community structures in sorghum rhizospheres cultivated in Cerrado soil.

PMID- 18070074
TI  - Genome-wide in silico mapping of the secretome in pathogenic Yersinia pestis KIM.
AB  - Uncovering the secretome of Yersinia pestis is a necessary measure to better
      understand the virulence of this plague-causing bacterium. Using bioinformatics
      methods, the components of all the secretion systems known to date in the Y.
      pestis KIM genome were mapped, including several systems identified by this
      study. It was found that this organism possesses Sec, twin-arginine
      translocation, signal recognition particle, Omp85/YaeT, type I, type II, type
      III, type VI, chaperone/usher, autotransporter, and two-partner secretion (TPS)
      systems, but lacks a type IV secretion system. The TPS systems caught the
      authors' attention, for they are used by several bacterial pathogens for the
      secretion of large virulence determinants. Reverse transcriptase-PCR analysis
      confirmed the gene expression of three TPS systems in Y. pestis KIM;
      bioinformatics studies indicated that the exoproteins of these TPS systems are
      putative hemolysins and adhesins. Results thus suggest that these are functional
      systems, capable of secreting virulence proteins that might contribute to plague
      infection. This is the first report on the complete secretome of pathogenic Y.
      pestis KIM.

PMID- 18070075
TI  - Parasitism of arbuscular mycorrhizal fungi: reviewing the evidence.
AB  - In order to understand the functioning of mycorrhizal fungi in ecosystems it is
      necessary to consider the full suite of possible biotic interactions in the soil.
      While a number of such interactions have recently been shown to be crucially
      important, parasitism is a highly neglected feature in the ecology of arbuscular
      mycorrhizal fungi (AMF). A number of studies have classified some interactions
      between populations of bacteria and fungi with AMF as parasitism, generating
      discussion about its consequences at both 'parasite' and host population levels.
      This paper reviews these various publications, and based on a set of criteria
      that are necessary to demonstrate parasitism, it was concluded that parasitism
      has not been conclusively shown to exist in AMF, even though some data are highly
      suggestive of such a relationship. The difficulties in gathering data supportive
      of parasitism were discussed, and hypotheses for defense were offered. This paper
      concludes by presenting potential consequences of AMF parasitism at the
      population/community levels and by discussing applied aspects.

PMID- 18070076
TI  - Construction of cholera toxin B subunit-producing Vibrio cholerae strains using
      the Mariner-FRT transposon delivery system.
AB  - The most widely used oral whole-cell-recombinant B subunit cholera vaccine
      contains the nontoxic cholera toxin B subunit (CTXB) and either heat- or formalin
      killed Vibrio cholerae O1 strains. Vibrio cholerae O1 strains in the vaccine
      provide antibacterial immunity, and CTXB contributes to the vaccine's efficacy by
      stimulating production of anti-CTXB antibody. Various attempts have been made to
      increase CTXB production. In this study, the mariner-FRT transposon delivery
      system developed by Chiang and Mekalanos was used to place the ctxB gene under
      the control of a strong chromosomal promoter in a nontoxigenic V. cholerae El Tor
      strain, M7922. The expression level of CTXB in transposon insertion mutant clones
      was screened by ganglioside-dependent enzyme-linked immunosorbent assay. Among
      CTXB-producing V. cholerae clones that were isolated, M7922-C1 produced the
      highest amount of CTXB (3.17+/-1.69 microg mL(-1)). M7922-C1 harbors a single
      insertion of ctxB into VC0972, which encodes a putative porin protein. Although
      the level of CTXB expression in this strain was not exceptionally high, this
      study indicates the possibility of using this delivery system to construct
      vaccine strains that overexpress specific antigens.

PMID- 18070077
TI  - Surface-active compounds and their role in the access to hydrocarbons in Gordonia
      strains.
AB  - Three new bacterial strains (M22, BS25 and BS29) belonging to the Gordonia genus
      were isolated from a site chronically contaminated by diesel. Those Gordonia
      strains were able to grow using a wide range of straight and branched aliphatic
      hydrocarbons as carbon and energy sources and to produce at least two classes of
      surface-active compounds. Emulsifying agents were released in the culture medium
      when bacteria grew both on hydrocarbons and water-soluble substrates. Cell-bound
      biosurfactants, which reduce the surface tension, were produced on hydrocarbons;
      however, their production was significantly lower on water soluble substrates.
      The relationship of growth phase, surface-active compound production and cell
      surface properties was analyzed in kinetic experiments on hydrocarbons. Gordonia
      sp. BS29 synthesized, and released extracellularly, bioemulsans during the
      exponential phase with n-hexadecane as carbon and energy source. The production
      of biosurfactants started in the exponential phase and their concentration
      increased during the following linear growth. Furthermore, the adhesion of
      bacterial cells to hydrocarbons decreased during growth. Our results led us to
      hypothesize a change in the mode by which Gordonia cells access the substrate
      during growth on hydrocarbons.

PMID- 18070078
TI  - Fucosyltransferase VII-positive, skin-homing T cells in the blood and skin
      lesions of atopic dermatitis patients.
AB  - Patients with atopic dermatitis (AD) have an abnormally increased frequency of
      cutaneous lymphocyte antigen (CLA)+ Th2 cells responsible for local inflammation;
      however, this is paradoxical, given the well-recognized defective capacity of Th2
      cells to migrate to the skin sites of inflammation. These discrepant observations
      would stem from the ambiguity of CLA+ T cells, because CLA does not represent the
      epitope required for binding to E-selectin but the epitope generated by
      fucosyltransferase VII (Fuc-TVII) and because skin-homing T cells are composed of
      three distinct subpopulations; Fuc-TVII+ E-selectin ligand (ESL)+ CLA-, Fuc-TVII+
      ESL+ CLA+ and Fuc-TVII- ESL- CLA+ cells. We therefore asked which subpopulations
      of skin-homing Th2 cells could be increased in the blood and skin lesions of AD.
      We analysed the frequencies of the three subpopulations in purified CD4+
      peripheral blood T cells from AD patients and healthy controls by
      immunohistochemistry and flow cytometry. The Fuc-TVII+ CLA+ or CLA+ ESL+ CCR4+
      cells were dramatically increased in frequency not only in the blood but also in
      the skin lesions of AD patients and this increase was related to the severity of
      the clinical symptoms. Our data indicate the clinical importance of identifying
      skin-homing T cells with the potent capacity to migrate into the skin by
      analysing their Fuc-TVII expression and E-selectin binding ability in patients
      with AD.

PMID- 18070079
TI  - Activation of chloride secretion via proteinase-activated receptor 2 in a human
      eccrine sweat gland cell line--NCL-SG3.
AB  - Proteinase-activated receptor 2 (PAR-2) has been shown to elicit secretion in a
      variety of secretory epithelial cells by the transepithelial movement of chloride
      ions across the apical membrane. However, it is not known whether these receptors
      are present and/or functional in the secretory epithelial cells of the human
      eccrine sweat gland. To investigate this possibility mRNA analysis, Ca2+
      microspectrofluorimetry and the short circuit current (Isc) technique were used
      to quantify electrolyte transport in a cell line (NCL-SG3) derived from human
      eccrine sweat gland secretory epithelia. The results provided molecular and
      functional evidence of the presence of PAR-2 receptors in the NCL-SG3 cells and
      show that these receptors can activate transepithelial Cl- secretion possibly via
      Ca2+-activated Cl- channels.

PMID- 18070080
TI  - Neurophysiological and neurochemical basis of modern pruritus treatment.
AB  - Chronic pruritus of any origin is a frequent discomfort in daily medical
      practice, and its therapy is challenging. Frequently, the underlying origin may
      not be identified and symptomatic therapy is necessary. Conventional treatment
      modalities such as antihistamines often lack efficacy, and hence new therapeutic
      strategies are necessary. The neuronal mechanisms underlying chronic pruritus
      have been partly identified during the past years and offer new therapeutic
      strategies. For example, mast cell degranulation, activation of neuroreceptors on
      sensory nerve fibres and neurogenic inflammation have been identified to be
      involved in induction and chronification of the symptom. Accordingly, controlling
      neuroreceptors such as cannabinoid receptors by agonists or antagonists showed
      high antipruritic efficacy. Pruritus is transmitted to the central nervous system
      by specialized nerve fibres and sensory receptors. It has been demonstrated that
      pruritus and pain have their own neuronal pathways with broad interactions.
      Accordingly, classical analgesics for neuropathic pain (gabapentin,
      antidepressants) also exhibit antipruritic efficacy upon clinical use. In
      summary, these recent developments show that highlighting the basis of pruritus
      offers modern neurophysiological and neurochemical therapeutic models and the
      possibility to treat patients with refractory itching of different origin.

PMID- 18070081
TI  - Expression of oestrogen-related receptor alpha in human epidermis.
AB  - Skin is a non-classical target for oestrogens. Despite evidence showing that
      oestrogen receptors (ER) are expressed in skin, there are still extensive gaps in
      our understanding of how oestrogens exert their action in non-reproductive
      tissues. Oestrogen-related receptor-alpha (ERRalpha), orphan member of the
      nuclear receptor superfamily, shows a strong sequence homology with ERalpha but
      it does not bind oestradiol. Here, for the first time, we demonstrate ERRalpha
      expression in the epidermis of adult human skin. ERRalpha mRNA was detected in
      the epidermis of eight female donors using reverse transcriptase polymerase chain
      reaction. The presence of the protein was confirmed using western blotting and
      immunohistochemistry on 5 and 11 adult human skins, respectively. This study
      shows that ERRalpha is expressed in human epidermis and could intervene in a
      potentially new oestrogen signalling pathway in the skin.

PMID- 18070082
TI  - A graft model for hair development.
AB  - Follicular cell implantation (FCI) is an experimental cell therapy for the
      treatment of hair loss that uses cultured hair follicle cells to induce new hair
      formation. This treatment is based on the demonstration that adult dermal papilla
      cells (DPC) retain the hair inductive capacity they acquired during hair
      morphogenesis in the embryo. For FCI, hair inductive cells are isolated from
      scalp biopsies and then propagated in culture in order to provide enough cells to
      generate many new follicles from a few donor follicles. Following expansion in
      culture, the cells are implanted into the scalp where they induce the formation
      of new follicles. Because the process relies on the ability to retain the
      potential for hair induction during the expansion of DPC in culture, we sought a
      consistent, reliable and easily performed in vivo assay in which to test hair
      induction. In this study, we describe a simple graft model that supports hair
      morphogenesis. The assay combines dermal cells with embryonic mouse epidermis
      that provides the keratinocyte component of induced follicles. The grafts are
      placed under a protective skin flap in the host athymic mouse where the cells
      will form a skin graft with hair if the dermal cells are hair inductive DPC.
      Using the assay, freshly isolated and cultured mouse embryo dermal cells as well
      as cultured dermal papilla cells from other species all induced hair formation.
      The induced hairs were aesthetically indistinguishable from those of the
      epidermal donor in length, thickness, and pigmentation, and they were
      histologically normal.

PMID- 18070083
TI  - Population structure, levels of selection, and the evolution of intracellular
      symbionts.
AB  - Many obligately intracellular symbionts exhibit a characteristic set of genetic
      changes that include an increase in substitution rates, loss of many genes, and
      apparent destabilization of many proteins and structural RNAs. Authors have
      suggested that these changes are due to increased mutation rates, or, more
      commonly, decreased effective population size due to population bottlenecks at
      the symbiont or, perhaps, host level. I propose that the increase in substitution
      rates and accumulation of deleterious mutations is a consequence of the
      population structure imposed on the endosymbionts by strict host association,
      loss of horizontal transmission and potentially conflicting levels of selection.
      I analyze a population genetic model of endosymbiont evolution, and demonstrate
      that substitution rates will increase, and the effect of those substitutions on
      endosymbiont fitness will become more deleterious as horizontal transmission
      among hosts decreases. Additionally, I find that there is a critical level of
      horizontal transmission below which natural selection cannot effectively purge
      deleterious mutations, leading to an expected loss of fitness over time. This
      critical level varies across loci with the degree of correlation between host and
      endosymbiont fitness, and may help explain differential retention and loss of
      certain genes.

PMID- 18070084
TI  - A worldwide polymorphism in aldehyde dehydrogenase in Drosophila melanogaster:
      evidence for selection mediated by dietary ethanol.
AB  - Clinally varying traits in Drosophila melanogaster provide good opportunities for
      elucidating the genetic basis of adaptation. Resistance to ethanol, a natural
      component of D. melanogaster's breeding sites, increases with latitude on
      multiple continents, indicating that the trait is under selection. Although the
      well-studied Alcohol dehydrogenase (Adh) polymorphism makes a contribution to the
      clines, it accounts for only a small proportion of the phenotypic variation. We
      describe an amino acid replacement polymorphism in Aldehyde dehydrogenase (Aldh),
      the gene encoding the second enzyme in the ethanol degradation pathway, that
      shows hallmarks of also contributing to the clines. The derived Aldh allele, like
      the Adh-Fast allele, increases in frequency in laboratory populations selected
      for ethanol resistance, and increases in frequency with latitude in wild
      populations. Moreover, strains with the derived allele have significantly higher
      ALDH enzyme activity with acetaldehyde (the breakdown product of ethanol) as a
      substrate than strains with the ancestral allele. As is the case with the Adh
      Fast allele, chromosomes with the derived Aldh allele show markedly reduced
      molecular variation in the vicinity of the replacement polymorphism compared to
      those with the ancestral allele, suggesting a single, relatively recent origin.
      Nonetheless, the Aldh polymorphism differs from the Adh polymorphism in that the
      ethanol-associated allele remains in relatively low frequency in most
      populations. We present evidence that this is likely to be the result of a trade
      off in catalytic activity, with the advantage of the derived allele in
      acetaldehyde detoxification being offset by a disadvantage in detoxification of
      other aldehydes.

PMID- 18070085
TI  - Intraspecific variation in sperm length is negatively related to sperm
      competition in passerine birds.
AB  - Spermatozoa are among the most diversified cells in the animal kingdom, but the
      underlying evolutionary forces affecting intraspecific variation in sperm
      morphology are poorly understood. It has been hypothesized that sperm competition
      is a potent selection pressure on sperm variation within species. Here, we
      examine intraspecific variation in total sperm length of 22 wild passerine bird
      species (21 genera, 11 families) in relation to the risk of sperm competition, as
      expressed by the frequency of extrapair paternity and relative testis size. We
      demonstrate, by using phylogenetic comparative methods, that between-male
      variation in sperm length within species is closely and negatively linked to the
      risk of sperm competition. This relationship was even stronger when only
      considering species in which data on sperm length and extrapair paternity
      originated from the same populations. Intramale variation in sperm length within
      species was also negatively, although nonsignificantly, related to sperm
      competition risk. Our findings suggest that postcopulatory sexual selection is a
      powerful evolutionary force reducing the intraspecific phenotypic variation in
      sperm-size traits, potentially driving the diversification of sperm morphology
      across populations and species.

PMID- 18070086
TI  - Sexual selection and immune function in Drosophila melanogaster.
AB  - The evolution of immune function depends not only on variation in genes
      contributing directly to the immune response, but also on genetic variation in
      other traits indirectly affecting immunocompetence. In particular, sexual
      selection is predicted to trade-off with immunocompetence because the extra
      investment of resources needed to increase sexual competitiveness reduces
      investment in immune function. Additional possible immunological consequences of
      intensifying sexual selection include an exaggeration of immunological sexual
      dimorphism, and the reduction of condition-dependent immunological costs due to
      selection of 'good genes' (the immunocompetence handicap hypothesis, ICHH). We
      tested for these evolutionary possibilities by increasing sexual selection in
      laboratory populations of Drosophila melanogaster for 58 generations by
      reestablishing a male-biased sex ratio at the start of each generation. Sexually
      selected flies were larger, took longer to develop, and the males were more
      sexually competitive than males from control (equal sex ratio) lines. We found
      support for the trade-off hypothesis: sexually selected males were found to have
      reduced immune function compared to control males. However, we found no evidence
      that sexual selection promoted immunological sexual dimorphism because females
      showed a similar reduction in immune function. We found no evidence of
      evolutionary changes in the condition-dependent expression of immunocompetence
      contrary to the expectations of the ICHH. Lastly, we compared males from the
      unselected base population that were either successful (IS) or unsuccessful (IU)
      in a competitive mating experiment. IS males showed reduced immune function
      relative to IU males, suggesting that patterns of phenotypic correlation largely
      mirror patterns of genetic correlation revealed by the selection experiment. Our
      results suggest increased disease susceptibility could be an important cost
      limiting increases in sexual competitiveness in populations experiencing intense
      sexual selection. Such costs may be particularly important given the high
      intersex correlation, because this represents an apparent genetic conflict,
      preventing males from reaching their sexually selected optimum.

PMID- 18070088
TI  - Global cognitive function in children with epilepsy: a community-based study.
AB  - PURPOSE: To determine the frequency and determinants of subnormal global
      cognitive function in a representative, community-based sample of children
      prospectively identified at the time of initial diagnosis of epilepsy. METHODS:
      In children enrolled with newly diagnosed epilepsy and followed a median of 10.5
      years, level of cognitive function (within normal, borderline, mild, moderate to
      severe mental retardation (MR), neurologically devastated, and impaired but not
      further classified (NFC)) was determined based upon neurologists' and school
      records, repeated parental interviews, and, in over half the participants,
      standardized neuropsychological testing. For multivariable analyses, subnormal
      cognitive function was designated as consistent with a full scale IQ < 80.
      RESULTS: Global cognitive function was considered within normal, N = 451 (73.6%),
      borderline, N = 31 (5.1%), mild MR, N = 21 (3.4%), more severe MR, N = 45 (7.3%),
      devastated, N = 29 (4.7%), and impaired-NFC, N = 36 (5.9%). Age at onset <5
      years, symptomatic etiology, epileptic encephalopathy, remission status and
      current AED treatment were each strongly associated with level of cognitive
      function (all p-values <0.0001). In a multivariable logistic regression model,
      all variables except remission status independently contributed to subnormal
      global cognitive function. DISCUSSION: Evidence of subnormal global cognitive
      function is apparent in approximately one of four children with epilepsy. Young
      age at onset, symptomatic cause, epileptic encephalopathy, and continued
      treatment, despite their strong intercorrelations, are independently associated
      with this outcome.

PMID- 18070089
TI  - Adiponectin and visfatin concentrations in children treated with valproic acid.
AB  - Chronic antiepileptic therapy with valproic acid (VPA) is associated with
      increased body weight and insulin resistance in adults and children. Attempts to
      determine the underlying pathophysiologic mechanisms have failed. Adipocytokines
      have recently been defined as a link between glucose and fat metabolism. We
      herein demonstrate that VPA-associated overweight is accompanied by lower
      adiponectin and higher leptin concentrations in children. The absence of any
      relationship with visfatin concentration does not suggest a role of this novel
      insulin-mimetic hormone in VPA-associated metabolic alterations. Therefore,
      adiponectin and leptin but not visfatin may be considered as potential regulators
      of glucose and fat metabolism during VPA-therapy.

PMID- 18070090
TI  - Are MRI-detected brain abnormalities associated with febrile seizure type?
AB  - OBJECTIVE: Whether magnetic resonance imaging (MRI) is informative in febrile
      seizures (FS) is unknown. We undertook a study to determine the frequency of MRI
      detected brain abnormalities and to evaluate their association with FS type and
      with specific features of complex FS. METHODS: A prospective cohort study, from
      1999 to 2004, included children with first FS from one Pediatric Emergency
      Department. MRI of the brain was performed within 1 week of the seizure. FS type
      was categorized by experts blind to the prior clinical history and MRI results.
      MRI examinations were read blind to the child's clinical history and FS type, and
      interviewers were blind to MRI results. RESULTS: In 159 children with a first FS,
      imaging abnormalities occurred in 12.6% (N = 20). Eight of the 54 with complex FS
      had imaging abnormalities compared to 12 of the 105 with simple FS (n.s.).
      Compared to children with simple FS, children with both focal and prolonged FS (N
      = 14) were more likely to have imaging abnormality (OR = 4.3, 95% CI = 1.2-15.0),
      even after adjustment for abnormal neurological examination. Imaging
      abnormalities included those known to be associated with seizures (e.g., focal
      cortical dysplasia) and those not typically associated with seizures (e.g.,
      subcortical focal hyperintensities > or = 5 mm). DISCUSSION: Our data suggest
      that brain abnormalities may lower seizure threshold in febrile children,
      predisposing to the development of FS. Clinical management was unaffected and
      therefore these data do not alter the recommendation that MRI is unnecessary in
      children with FS, without some other neurological indication.

PMID- 18070092
TI  - Do patients with psychogenic nonepileptic seizures produce trustworthy findings
      on neuropsychological tests?
AB  - Drane et al. (2006) has recently raised the possibility that patients with
      psychogenic nonepileptic seizures (PNES) may make poor effort in taking
      neuropsychological tests in comparison with patients with epilepsy (ES).
      Therefore, findings previously reported with PNES patients may be in error,
      especially with regard to tests of mental abilities. Using the same measure of
      effort used by Drane et al. (2006) but with more broadly selected patients, this
      paper attempts to replicate their findings with new samples of ES (n = 65) and
      PNES (n = 32) cases. However, their findings could not be replicated, and no
      differences in test taking effort could be demonstrated across the groups. The
      highly selected samples of Drane et al. (2006) appear to be responsible for their
      results, and neuropsychological findings with PNES patients appear to be as
      trustworthy as those with ES patients.

PMID- 18070091
TI  - Early treatment suppresses the development of spike-wave epilepsy in a rat model.
AB  - PURPOSE: Current treatments for epilepsy may control seizures, but have no known
      effects on the underlying disease. We sought to determine whether early treatment
      in a model of genetic epilepsy would reduce the severity of the epilepsy
      phenotype in adulthood. METHODS: We used Wistar albino Glaxo rats of Rijswijk
      (WAG/Rij) rats, an established model of human absence epilepsy. Oral ethosuximide
      was given from age p21 to 5 months, covering the usual period in which seizures
      develop in this model (age approximately 3 months). Two experiments were
      performed: (1) cortical expression of ion channels Nav1.1, Nav1.6, and HCN1
      (previously shown to be dysregulated in WAG/Rij) measured by immunocytochemistry
      in adult treated rats; and (2) electroencephalogram (EEG) recordings to measure
      seizure severity at serial time points after stopping the treatment. RESULTS:
      Early treatment with ethosuximide blocked changes in the expression of ion
      channels Nav1.1, Nav1.6, and HCN1 normally associated with epilepsy in this
      model. In addition, the treatment led to a persistent suppression of seizures,
      even after therapy was discontinued. Thus, animals treated with ethosuximide from
      age p21 to 5 months still had a marked suppression of seizures at age 8 months.
      DISCUSSION: These findings suggest that early treatment during development may
      provide a new strategy for preventing epilepsy in susceptible individuals. If
      confirmed with other drugs and epilepsy paradigms, the availability of a model in
      which epileptogenesis can be controlled has important implications both for
      future basic studies, and human therapeutic trials.

PMID- 18070093
TI  - Do observer and self-reports of ictal eye closure predict psychogenic
      nonepileptic seizures?
AB  - PURPOSE: Diagnostic delay in distinguishing psychogenic nonepileptic seizures
      (PNES) from epileptic seizures may result in unnecessary therapeutic
      interventions and higher health care costs. Previous studies demonstrated that
      video-recorded eye closure is associated with PNES. The present study
      prospectively assessed whether observer or self-report of eye closure could
      predict PNES, prior to video-EEG monitoring. METHODS: Adults referred to an
      epilepsy monitoring unit (EMU) were prospectively enrolled into the study. At
      baseline, self-report of eye closure was assessed by questionnaire, and observer
      report was obtained by interview. Physicians viewed video clips independent of
      EEG tracings and determined the duration of eye closure during PNES and epileptic
      seizures. We evaluated whether video-recorded eye closure identified an episode
      as PNES using random effects models that accounted for episode clustering by
      subject. The utility of observer and self-report of eye closure in predicting a
      diagnosis of PNES was tested using logistic regression. RESULTS: Of 132 enrolled
      subjects, 112 met study criteria during EMU stay for either PNES (n = 43, 38.4%)
      or epilepsy (n = 84, 75.0%). Fifteen of the 43 PNES subjects (34.9%) had
      coexisting epilepsy. Self and observer reports of eye closure were neither
      sensitive nor specific for the diagnosis of PNES. Self-report of eye closure more
      accurately predicted actual video-recorded eye closure than observer report.
      Video-recorded eye closure was 92% specific, but only 64% sensitive for PNES
      identification. DISCUSSION: Neither observer nor self-report of eye closure,
      prior to VEEG monitoring, predicts PNES. Video-recorded eye closure may not be as
      sensitive an indicator of PNES as previously reported.

PMID- 18070094
TI  - Addressing genetic heterogeneity in complex disease: finding seizure genes in
      systemic lupus erythematosus.
AB  - Complex genetic disease is inherently difficult to study due to an imperfect
      relationship between genotype and phenotype. One important reason for this
      imperfect relationship is genetic heterogeneity, the occurrence of different
      genetic factors underlying the same clinical syndrome. One method of addressing
      genetic heterogeneity is covariate-based linkage analysis, which allows the use
      of additional phenotypic features to define genetically distinct subsets of
      patients. Systemic lupus erythematosus (SLE) is one example of a complex genetic
      disease affecting multiple organ systems including the central nervous system. We
      report here the use of covariate-based linkage analysis to detect a potential
      genetic locus on chromosome 15 influencing the development of seizures in
      individuals with SLE. The use of covariates increases the power to detect linkage
      in the presence of genetic heterogeneity.

PMID- 18070095
TI  - Efficacy of the ketogenic diet in the 6-Hz seizure test.
AB  - PURPOSE: Since the ketogenic diet is effective in drug-resistant epilepsies, we
      sought to determine whether it is active in the 6-Hz seizure test, which
      identifies agents with a broader spectrum of activity than conventional
      antiepileptic screening tests. METHODS: Male (3-4 week old) NIH Swiss mice were
      fed a normal or ketogenic diet ad libitum for 2-21 days. The intensity of the
      corneal stimulation current required to elicit seizures in the 6-Hz test was
      measured. Blood glucose and beta-hydroxybutyrate were measured on the day of
      seizure testing. RESULTS: CC(50) (current intensity producing seizures in 50% of
      mice tested) was 50.6 mA and 15 mA in mice fed for 12 days with a ketogenic or
      normal diet, respectively (p < 0.001). CC(50) was elevated in separate
      experiments after 16, but not 2, 5, and 21 days of ketogenic diet exposure.
      CC(50) values of growing mice fed the normal diet does not differ, indicating
      CC(50) does not vary with mouse weight during a rapid growth phase. beta
      Hydroxybutyrate was significantly higher, and glucose was significantly lower in
      mice fed the ketogenic diet than those fed the normal diet. Blood glucose and
      beta-hydroxybutyrate levels did not correlate with CC(50). DISCUSSION: The
      ketogenic diet significantly elevates the seizure threshold in the 6-Hz test in a
      time-specific manner. Protection from seizures in this model was not related to
      level of ketosis. CC(50) was insensitive to body weight in mice fed the normal
      diet, demonstrating that the 6-Hz model can assess anticonvulsant regimens where
      weight is a confounding factor.

PMID- 18070097
TI  - Planktonic dispersal dampens temporal trophic cascades in pond metacommunities.
AB  - Trophic cascades, in which changes in predation affect the biomass of lower
      trophic levels, vary substantially in strength and incidence. Most work to
      explain this variation has focused on local factors and has ignored larger
      regional effects. To study how metacommunity dynamics can alter trophic cascades,
      we constructed mesocosm metacommunities consisting of three pond communities with
      heterogeneous levels of fish predation and examined how planktonic dispersal rate
      (5-140% per week) affected biomass partitioning. Two of the three communities
      differed continually in the occurrence of fish and supported different but
      constant environments in a 'spatial trophic cascade,' while the third community
      supported temporally variable fish occurrence in a 'temporal trophic cascade.' We
      find that the presence, but the not the magnitude, of dispersal dampens temporal
      trophic cascades through an increase in grazer biomass. In contrast, dispersal
      has no effect on the strength of spatial cascades due to strong sorting pressures
      in the communities with constant presence or absence of fish as top predators.

PMID- 18070096
TI  - Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot
      trial.
AB  - Although statins are being used for secondary prevention of ischemic stroke,
      recent experimental data have shown new pleiotropic effects of these drugs
      responsible for their role in neuroprotection. We conducted a pilot, double
      blind, randomized, multicenter clinical trial to study for the first time safety
      and efficacy of simvastatin in the acute phase of ischemic stroke.
      Simvastatin/placebo was given at 3-12 h from symptom onset to 60 patients with
      cortical strokes. Efficacy on the evolution of several inflammation markers
      [interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1,
      intercellular adhesion molecule-1, vascular cell adhesion molecule-1, C-reactive
      protein, sApo/Fas, tumor necrosis factor-alpha, E-selectin, L-selectin and
      nitrites+nitrates] and neurological outcome was evaluated at baseline, day 1, 3,
      5, 7 and 90. No differences were found amongst the biomarkers studied regarding
      treatment allocation. Although simvastatin patients improved significantly by the
      third day (46.4% vs. 17.9%, P = 0.022), a non-significant increase in mortality
      and greater proportion of infections (odds ratio 2.4, confidence interval 1.06
      5.4) in the simvastatin group were the main safety concerns. Therefore, a larger
      clinical trial is needed to confirm the net benefit of this therapeutic approach.

PMID- 18070099
TI  - Antagonistic effects of a Mhc class I allele on malaria-infected house sparrows.
AB  - Genes of the Major Histocompatibility Complex (Mhc) play a fundamental role
      during the immune response because MHC molecules expressed on cell surface allow
      the recognition and presentation of antigenic peptides to T-lymphocytes. Although
      Mhc alleles have been found to correlate with pathogen resistance in several host
      parasite systems, several studies have also reported associations between Mhc
      alleles and an accrued infection risk or an accelerated disease progression. The
      existence of these susceptibility alleles is puzzling, as the cost generated by
      the infection should rapidly eliminate them from the population. Here, we show
      that susceptibility alleles may be maintained in a population of house sparrows
      (Passer domesticus) if they have antagonistic effects on different malaria
      parasites. We found that one Mhc class I allele was associated with a 2.5-fold
      increase in the risk to be infected with a Plasmodium strain, but with a 6.4-fold
      reduction in the risk to harbour a Haemoproteus strain. We suggest that this
      antagonistic effect might arise because Mhc genes can alter the competitive
      interactions between malaria parasites within the host.

PMID- 18070098
TI  - Prediction uncertainty of environmental change effects on temperate European
      biodiversity.
AB  - Observed patterns of species richness at landscape scale (gamma diversity) cannot
      always be attributed to a specific set of explanatory variables, but rather
      different alternative explanatory statistical models of similar quality may
      exist. Therefore predictions of the effects of environmental change (such as in
      climate or land cover) on biodiversity may differ considerably, depending on the
      chosen set of explanatory variables. Here we use multimodel prediction to
      evaluate effects of climate, land-use intensity and landscape structure on
      species richness in each of seven groups of organisms (plants, birds, spiders,
      wild bees, ground beetles, true bugs and hoverflies) in temperate Europe. We
      contrast this approach with traditional best-model predictions, which we show,
      using cross-validation, to have inferior prediction accuracy. Multimodel
      inference changed the importance of some environmental variables in comparison
      with the best model, and accordingly gave deviating predictions for environmental
      change effects. Overall, prediction uncertainty for the multimodel approach was
      only slightly higher than that of the best model, and absolute changes in
      predicted species richness were also comparable. Richness predictions varied
      generally more for the impact of climate change than for land-use change at the
      coarse scale of our study. Overall, our study indicates that the uncertainty
      introduced to environmental change predictions through uncertainty in model
      selection both qualitatively and quantitatively affects species richness
      projections.

PMID- 18070100
TI  - Global variation in diversification rates of flowering plants: energy vs. climate
      change.
AB  - We used the largest DNA-based phylogeny of flowering plants to date to evaluate
      the importance of energy vs. past climate change in predicting global patterns in
      diversification. Relative diversification rates increased towards the equator,
      suggesting that differences in per-lineage net diversification may be an
      important component of the latitudinal diversity gradient. The amplitude of
      Quaternary climate oscillations experienced by families explained variation in
      diversification equally well compared to contemporary energy measures, and energy
      and climate change measures were intercorrelated, making it difficult to reject
      either as a causal mechanism. Many putative mechanisms linking diversification to
      energy availability do not apply to plants, whereas the climate change mechanism
      has more support. We also present the first global map of angiosperm
      diversification, showing that, after correcting for family range-size, tropical
      diversification rates were fastest for clades currently in regions with high
      endemic species richness outside the main lowland rainforest areas.

PMID- 18070101
TI  - Network structural properties mediate the stability of mutualistic communities.
AB  - Key advances are being made on the structures of predator-prey food webs and
      competitive communities that enhance their stability, but little attention has
      been given to such complexity-stability relationships for mutualistic
      communities. We show, by way of theoretical analyses with empirically informed
      parameters, that structural properties can alter the stability of mutualistic
      communities characterized by nonlinear functional responses among the interacting
      species. Specifically, community resilience is enhanced by increasing community
      size (species diversity) and the number of species interactions (connectivity),
      and through strong, symmetric interaction strengths of highly nested networks. As
      a result, mutualistic communities show largely positive complexity-stability
      relationships, in opposition to the standard paradox. Thus, contrary to the
      commonly-held belief that mutualism's positive feedback destabilizes food webs,
      our results suggest that interplay between the structure and function of
      ecological networks in general, and consideration of mutualistic interactions in
      particular, may be key to understanding complexity-stability relationships of
      biological communities as a whole.

PMID- 18070102
TI  - Self-structuring in spatial evolutionary ecology.
AB  - Spatial self-structuring has been a focus of recent interest among evolutionary
      ecologists. We review recent developments in the study of the interplay between
      spatial self-structuring and evolution. We first discuss the relative merits of
      the various theoretical approaches to spatial modelling in ecology. Second, we
      synthesize the main theoretical studies of the evolution of cooperation in
      spatially structured populations. We show that population viscosity is generally
      beneficial to cooperation, because cooperators can reap additional benefits from
      being clustered. A similar mechanism can explain the evolution of honest
      communication and of reduced virulence in host-parasite interactions. We also
      discuss some recent innovative empirical results that test these theories. Third,
      we show the relevance of these results to the general field of evolutionary
      ecology. An important conclusion is that kin selection is the main process that
      drives evolution of cooperation in viscous populations. Many results of kin
      selection theory can be recovered as emergent properties of spatial ecological
      dynamics. We discuss the implications of these results for the study of
      multilevel selection and evolutionary transitions. We conclude by sketching some
      perspectives for future research, with a particular emphasis on the topics of
      evolutionary branching, criticality, spatial fluctuations and experimental tests
      of theoretical predictions. Space is the place - Sun Ra.

PMID- 18070103
TI  - Effects of the G376E and G157D mutations on the stability of yeast enolase--a
      model for human muscle enolase deficiency.
AB  - The first known human enolase deficiency was reported in 2001 [Comi GP, Fortunato
      F, Lucchiari S, Bordoni A, Prelle A, Jann S, Keller A, Ciscato P, Galbiati S,
      Chiveri L et al. (2001) Ann Neurol50, 202-207]. The subject had inherited two
      mutated genes for beta-enolase. These mutations changed glycine 156 to aspartate
      and glycine 374 to glutamate. In order to study the effects of these changes on
      the structure and stability of enolase, we have introduced the corresponding
      changes (G157D and G376E) into yeast enolase. The two variants are correctly
      folded. They are less stable than wild-type enolase with respect to thermal
      denaturation, and both have increased Kd values for subunit dissociation. At 37
      degrees C, in the presence of salt, both are partially dissociated and are
      extensively cleaved by trypsin. Under the same conditions, wild-type enolase is
      fully dimeric and is only slightly cleaved by trypsin. However, wild-type enolase
      is also extensively cleaved if it is partially dissociated. The identification of
      the cleavage sites and spectral studies of enolase have revealed some of the
      structural differences between the dimeric and monomeric forms of this enzyme.

PMID- 18070104
TI  - Trehalose and anhydrobiosis in tardigrades--evidence for divergence in responses
      to dehydration.
AB  - To withstand desiccation, many invertebrates such as rotifers, nematodes and
      tardigrades enter a state known as anhydrobiosis, which is thought to require
      accumulation of compatible osmolytes, such as the non-reducing disaccharide
      trehalose to protect against dehydration damage. The trehalose levels of eight
      tardigrade species comprising Heterotardigrada and Eutardigrada were observed in
      five different states of hydration and dehydration. Although many species
      accumulate trehalose during dehydration, the data revealed significant
      differences between the species. Although trehalose accumulation was found in
      species of the order Parachela (Eutardigrada), it was not possible to detect any
      trehalose in the species Milnesium tardigradum and no change in the trehalose
      level has been observed in any species of Heterotardigrada so far investigated.
      These results expand our current understanding of anhydrobiosis in tardigrades
      and, for the first time, demonstrate the accumulation of trehalose in developing
      tardigrade embryos, which have been shown to have a high level of desiccation
      tolerance.

PMID- 18070105
TI  - Characterization of recombinant prolidase from Lactococcus lactis- changes in
      substrate specificity by metal cations, and allosteric behavior of the peptidase.
AB  - The Lactococcus lactis NRRL B-1821 prolidase gene was cloned and overexpressed in
      Escherichia coli. Under suboptimum growth conditions, recombinant soluble and
      active prolidase was produced; in contrast, inclusion bodies were formed under
      conditions preferred for cell growth. Recombinant prolidase retained more than
      half its full activity between 30 and 60 degrees C, and was completely
      inactivated after 30 min at 70 degrees C. CD analysis confirmed that prolidase
      was inactivated at 67 degrees C. The enzyme was active under weak alkali to weak
      acidic conditions, and showed maximum activity at pH 7.0. Although these
      characteristics are similar to those for other reported prolidases, this
      prolidase was distinctive for two kinetic characteristics. Firstly, different
      substrate specificity was observed for its two preferred metal cations, zinc and
      manganese: Leu-Pro was preferred with zinc, whereas Arg-Pro was preferred with
      manganese. Secondly, the enzyme showed an allosteric response to changes in
      substrate concentrations, with Hill constants of 1.53 for Leu-Pro and 1.57 for
      Arg-Pro. Molecular modeling of this prolidase suggests that these unique
      characteristics may be attributed to a loop structure near the active site.

PMID- 18070106
TI  - Putative prion protein from Fugu (Takifugu rubripes).
AB  - Prion proteins (PrP) of mammals, birds, reptiles and amphibians have been
      successfully cloned, expressed and purified in sufficient yields to enable 3D
      structure determination by NMR spectroscopy in solution. More recently, PrP
      ortholog genes have also been identified in several fish species, based on
      sequence relationships with tetrapod PrPs. Even though the sequence homology of
      fish PrPs to tetrapod PrPs is below 25%, structure prediction programs indicate a
      similar organization of the 3D structure. In this study, we generated recombinant
      polypeptide constructs that were expected to include the C-terminal folded domain
      of Fugu-PrP1 and analyzed these proteins using biochemical and biophysical
      methods. Because soluble expression could not be achieved, and refolding from
      guanidine-HCl did not result in a properly folded protein, we co-expressed
      Escherichia coli chaperone proteins in order to obtain the protein in a soluble
      form. Although CD spectroscopy indicated the presence of some regular secondary
      structure in the protein thus obtained, there was no evidence for a globular 3D
      fold in the NMR spectra. We thus conclude that the polypeptide products of the
      fish genes annotated as corresponding to bona fide prnp genes in non-fish species
      cannot be prepared for structural studies when using procedures similar to those
      that were successfully used with PrPs from mammals, birds, reptiles and
      amphibians.

PMID- 18070107
TI  - Inactive forms of the catalytic subunit of protein kinase A are expressed in the
      brain of higher primates.
AB  - It is well documented that the beta-gene of the catalytic (C) subunit of protein
      kinase A encodes a number of splice variants. These splice variants are equipped
      with a variable N-terminal end encoded by alternative use of several exons
      located 5' to exon 2 in the human, bovine and mouse Cbeta gene. In the present
      study, we demonstrate the expression of six novel human Cbeta mRNAs that lack 99
      bp due to loss of exon 4. The novel splice variants, designated CbetaDelta4, were
      identified in low amounts at the mRNA level in NTera2-N cells. We developed a
      method to detect CbetaDelta4 mRNAs in various cells and demonstrated that these
      variants were expressed in human and Rhesus monkey brain. Transient expression
      and characterization of the CbetaDelta4 variants demonstrated that they are
      catalytically inactive both in vitro against typical protein kinase A substrates
      such as kemptide and histone, and in vivo against the cAMP-responsive element
      binding protein. Furthermore, co-expression of CbetaDelta4 with the regulatory
      subunit (R) followed by kinase activity assay with increasing concentrations of
      cAMP and immunoprecipitation with extensive washes with cAMP (1 mm) and
      immunoblotting demonstrated that the CbetaDelta4 variants associate with both RI
      and RII in a cAMP-independent fashion. Expression of inactive C subunits which
      associate irreversibly with R may imply that CbetaDelta4 can modulate local cAMP
      effects in the brain by permanent association with R subunits even at saturating
      concentrations of cAMP.

PMID- 18070108
TI  - Type I receptor binding of bone morphogenetic protein 6 is dependent on N
      glycosylation of the ligand.
AB  - Bone morphogenetic proteins (BMPs), together with transforming growth factor
      (TGF)-beta and activins/inhibins, constitute the TGF-beta superfamily of ligands.
      This superfamily is formed by more than 30 structurally related secreted
      proteins. The crystal structure of human BMP-6 was determined to a resolution of
      2.1 A; the overall structure is similar to that of other TGF-beta superfamily
      ligands, e.g. BMP-7. The asymmetric unit contains the full dimeric BMP-6,
      indicating possible asymmetry between the two monomeric subunits. Indeed, the
      conformation of several loops differs between both monomers. In particular, the
      prehelix loop, which plays a crucial role in the type I receptor interactions of
      BMP-2, adopts two rather different conformations in BMP-6, indicating possible
      dynamic flexibility of the prehelix loop in its unbound conformation. Flexibility
      of this loop segment has been discussed as an important feature required for
      promiscuous binding of different type I receptors to BMPs. Further studies
      investigating the interaction of BMP-6 with different ectodomains of type I
      receptors revealed that N-glycosylation at Asn73 of BMP-6 in the wrist epitope is
      crucial for recognition by the activin receptor type I. In the absence of the
      carbohydrate moiety, activin receptor type I-mediated signaling of BMP-6 is
      totally diminished. Thus, flexibility within the binding epitope of BMP-6 and an
      unusual recognition motif, i.e. an N-glycosylation motif, possibly play an
      important role in type I receptor specificity of BMP-6.

PMID- 18070109
TI  - Identification of rice TUBBY-like genes and their evolution.
AB  - The identification of TUBBY-like genes in organisms ranging from single-celled to
      multicellular eukaryotes has allowed the phylogenetic history of this gene family
      to be traced back to the early evolutionary stages of eukaryote development. Rice
      TUBBY-like genes were located on chromosomes 1, 2, 3, 4, 5, 7, 8, 11 and 12
      without any obvious clustering. On a genomic scale, it was revealed that the rice
      TUBBY-like gene family probably evolved mainly through segmental duplication
      produced by polyploidy. The altered selective constraints (or site-specific rate
      changes), related to functional divergence during protein evolution between plant
      and animal TUBBY-like genes, were statistically significant. Based on posterior
      probability analysis, five amino acid sites (103, 312, 315, 317 and 319) are
      thought to be responsible for functional divergence.

PMID- 18070110
TI  - Development of three-dimensional architecture of the neuroepithelium: role of
      pseudostratification and cellular 'community'.
AB  - This review discusses the development of the neuroepithelium (NE) and its
      derivative ventricular zone (VZ), from which the central nervous system (CNS) is
      formed. First, the histological features of the NE and VZ are summarized,
      highlighting the phenomenon of pseudostratification, which is achieved by
      polarization and interkinetic nuclear migration (INM) of neural progenitor cells.
      Next, our current understanding of the cellular and molecular mechanisms and
      biological significance of INM and pseudostratification are outlined. The recent
      three-dimensional time-lapse observations revealing heterogeneity in cell
      lineages within the NE and VZ are also described, focusing on the neuronal
      lineage. Finally, the necessity of comprehensive studies on cell-cell
      interactions in the NE/VZ is discussed, as well as the importance of
      electrophysiological and biomechanical approaches. In particular, we suggest that
      a systems biology approach to the NE/VZ as a cellular 'community' may be
      fruitful.

PMID- 18070111
TI  - Higher diagnostic accuracy with the ThinPrep method in a simulated intraoperative
      environment.
AB  - OBJECTIVE: To compare the accuracy of intraoperative fine needle aspiration
      cytology samples prepared by the ThinPrep method to conventional cytological
      methods. Specimen adequacy and turn around time (TAT) were also assessed.
      METHODS: Fifty consecutive fresh tumours submitted for histological analysis were
      aspirated and each prepared as follows: (i) direct smear with H&E stain, (ii)
      direct smear with Pap stain, (iii) ThinPrep slide with H&E stain, and (iv)
      ThinPrep slide with Pap stain. The slides were randomly distributed to three
      cytopathologists for interpretation. The quality of the preparation, the
      diagnosis and the time needed for interpretation were recorded. RESULTS: Accuracy
      was measured as the percentage of absolute agreement between the cytological and
      the histopathological diagnoses of the lesions. Histologically, there were 43
      malignant and six benign lesions and one atypical lipoma. The TAT began when the
      slides/cytolyte specimens arrived at the lab and ended with the pathologist's
      diagnosis. CONCLUSIONS: In terms of accuracy and specimen adequacy, ThinPrep
      slides with Pap stain is the best procedure. This advantage however is offset by
      the longer testing time.

PMID- 18070112
TI  - S-phase fraction determined on fine needle aspirates is an independent prognostic
      factor in breast cancer - a multivariate study of 770 patients.
AB  - BACKGROUND: The prognostic significance of DNA ploidy and the S-phase fraction
      (SPF) have been extensively studied in breast cancer, but their clinical utility
      remains controversial. The type of tumour material can substantially influence
      flow cytometric DNA measurements. Material obtained by fine needle aspiration
      (FNA) biopsy is very suitable for flow cytometric DNA analysis because it
      contains a low proportion of non-tumour cells and less debris than tissue
      samples. METHODS: The prognostic significance of DNA ploidy and SPF, determined
      on FNA samples, was analysed in 770 breast cancer patients, diagnosed between
      1992 and 1997. DNA ploidy and SPF were determined at the time of diagnosis as
      part of the diagnostic work-up. The median follow-up was 90 months. Survival
      analysis included overall cancer specific survival (OS), disease free survival
      (DFS) and survival after recurrence (SAR). Other variables included in survival
      analyses were age, histological grade, histological type, lymph node status and
      tumour size. Disease free interval and the site of recurrence were also included
      in SAR analysis. RESULTS: DNA ploidy and SPF correlated with tumour type, size,
      lymph node involvement and, especially, tumour grade. In a univariate analysis,
      both aneuploidy and high SPF were associated with shorter OS, DFS and SAR, but
      only SPF retained its independent prognostic significance in multivariate
      analyses. Independent prognostic variables for OS were node status, histological
      grade, SPF and tumour size. Node status, histological grade and SPF were
      independent predictors of DFS, while the site of recurrence, SPF, histological
      grade, disease free interval and age were independent predictors of SAR.
      CONCLUSIONS: DNA ploidy and SPF can be efficiently and routinely determined on
      FNA samples. High SPF is independently associated with a worse clinical outcome
      of patients with breast cancer. Although SPF and histological grade share
      prognostic information to some degree, SPF provides additional, less subjective
      prognostic information. The prognostic value of SPF determined on FNA samples
      could be even more relevant in neoadjuvant settings and for patients not amenable
      for surgical treatment, when histological grade cannot be assessed.

PMID- 18070113
TI  - Incidental findings in bronchial lavage fluid?

PMID- 18070114
TI  - Fine needle aspiration of a mesenteric mass.

PMID- 18070115
TI  - Acinic cell carcinoma-papillary cystic variant. Pitfalls of fine needle
      aspiration diagnosis: study of five cases and review of literature.
AB  - OBJECTIVES: Acinic cell carcinoma (ACC) accounts for 12-17% of primary salivary
      gland carcinomas and 3.4% of all salivary gland neoplasms. ACC-papillary cystic
      variant (PCV) is a distinct subtype with clear-cut and well-defined morphological
      features as revealed in tissue sections, but it is more difficult to diagnose
      accurately on fine needle aspiration (FNA). The aim of this article was to
      discuss the causes of the erroneous interpretation as well as to draw attention
      of practicing pathologists to this rare and unique variant of ACC. METHODS: A
      computerized search of surgical and cytopathology files identified five diagnoses
      of ACC-PCV that were preceded by an FNA performed in-house with available slides
      for review. Cytological features were compared to histomorphological features of
      excisional surgical pathology specimens. RESULTS: Cytomorphological findings from
      these ACC-PCV cases have varied features that can be broadly divided in two major
      subtypes: hypocellular cystic specimens containing histiocyte-like vacuolated
      cells (two cases) and more cellular specimens containing papillary clusters of
      cells with a polymorphous appearance including granular cells, vacuolated cells
      and nondescript small cuboidal cells (three cases). CONCLUSIONS: Hypocellular,
      cyst-like specimens pose a diagnostic problem when using FNA, as they can easily
      be misinterpreted as a benign cyst of the salivary gland. Our review of cases
      found certain 'red flags' that should prompt pathologists to further investigate
      the true acinic origin of hypocellular cystic specimens. On close morphological
      examination, these specimens revealed the presence of tight cellular clusters,
      distinct cytoplasmic borders, larger nuclei with distinct nucleoli and
      binucleated cells.

PMID- 18070116
TI  - Multiple cutaneous relapses in an adolescent in anaplastic large cell lymphoma
      diagnosed by FNAC.

PMID- 18070117
TI  - The Leishmania-macrophage interaction: a metabolic perspective.
AB  - Protozoan parasites belonging to the genus Leishmania exhibit a pronounced
      tropism for macrophages although they have the capacity to infect a variety of
      other phagocytic and non-phagocytic mammalian cells. Unlike most other
      intramacrophage pathogens, the major proliferative stage of Leishmania resides in
      the mature phagolysosomes of these host cells. In this review we highlight some
      of the strategies utilized by the intracellular amastigote stage of Leishmania to
      survive in this compartment. Remarkably, and in contrast to many other
      intracellular pathogens, Leishmania amastigotes have a minimalist surface
      glycocalyx which may facilitate uptake of essential lipids and promote exposure
      of phospholipids required for phagocytosis via macrophage apoptotic cell
      receptors. Leishmania amastigotes also differ from many other intracellular
      pathogens in having complex nutritional requirements which must be scavenged from
      the host cell. Amino acids and polyamines appear to be important carbon sources
      and growth-limiting nutrients, respectively, and their availability to
      intracellular amastigotes may be regulated by the activation state of host
      macrophages. Metabolic processes in both the parasite and host cell may thus be
      crucial determinants of disease outcome.

PMID- 18070118
TI  - Iron acquisition within host cells and the pathogenicity of Leishmania.
AB  - Iron is an essential cofactor for several enzymes and metabolic pathways, in both
      microbes and in their eukaryotic hosts. To avoid toxicity, iron acquisition is
      tightly regulated. This represents a particular challenge for pathogens that
      reside within the endocytic pathway of mammalian cells, because endosomes and
      lysosomes are gradually depleted in iron by host transporters. An important
      player in this process is Nramp1 (Slc11a1), a proton efflux pump that
      translocates Fe(2+) and Mn(2+) ions from macrophage lysosomes/phagolysosomes into
      the cytosol. Mutations in Nramp1 cause susceptibility to infection with the
      bacteria Salmonella and Mycobacteria and the protozoan Leishmania, indicating
      that an available pool of intraphagosomal iron is critical for the intracellular
      survival and replication of these pathogens. Salmonella and Mycobacteria are
      known to express iron transporter systems that effectively compete with host
      transporters for iron. Until recently, however, very little was known about the
      molecular strategy used by Leishmania for survival in the iron-poor environment
      of macrophage phagolysosomes. It is now clear that intracellular residence
      induces Leishmania amazonensis to express LIT1, a ZIP family membrane Fe(2+)
      transporter that is required for intracellular growth and virulence.

PMID- 18070119
TI  - The mannose cap of mycobacterial lipoarabinomannan does not dominate the
      Mycobacterium-host interaction.
AB  - Pathogenic mycobacteria have the ability to persist in phagocytic cells and to
      suppress the immune system. The glycolipid lipoarabinomannan (LAM), in particular
      its mannose cap, has been shown to inhibit phagolysosome fusion and to induce
      immunosuppressive IL-10 production via interaction with the mannose receptor or
      DC-SIGN. Hence, the current paradigm is that the mannose cap of LAM is a crucial
      factor in mycobacterial virulence. However, the above studies were performed with
      purified LAM, never with live bacteria. Here we evaluate the biological
      properties of capless mutants of Mycobacterium marinum and M. bovis BCG, made by
      inactivating homologues of Rv1635c. We show that its gene product is an
      undecaprenyl phosphomannose-dependent mannosyltransferase. Compared with parent
      strain, capless M. marinum induced slightly less uptake by and slightly more
      phagolysosome fusion in infected macrophages but this did not lead to decreased
      survival of the bacteria in vitro, nor in vivo in zebra fish. Loss of caps in M.
      bovis BCG resulted in a sometimes decreased binding to human dendritic cells or
      DC-SIGN-transfected Raji cells, but no differences in IL-10 induction were
      observed. In mice, capless M. bovis BCG did not survive less well in lung, spleen
      or liver and induced a similar cytokine profile. Our data contradict the current
      paradigm and demonstrate that mannose-capped LAM does not dominate the
      Mycobacterium-host interaction.

PMID- 18070120
TI  - A systematic review of the survival and complication rates of resin-bonded
      bridges after an observation period of at least 5 years.
AB  - OBJECTIVES: The objectives of this systematic review were to assess the 5-year
      survival of resin-bonded bridges (RBBs) and to describe the incidence of
      technical and biological complications. METHODS: An electronic Medline search
      complemented by manual searching was conducted to identify prospective and
      retrospective cohort studies on RBBs with a mean follow-up time of at least 5
      years. Patients had to have been examined clinically at the follow-up visit.
      Assessment of the identified studies and data extraction were performed
      independently by two reviewers. Failure and complication rates were analyzed
      using random-effects Poissons regression models to obtain summary estimates of 5
      year proportions. RESULTS: The search provided 6110 titles and 214 abstracts.
      Full-text analysis was performed for 93 articles, resulting in 17 studies that
      met the inclusion criteria. Meta-analysis of these studies indicated an estimated
      survival of RBBs of 87.7% (95% confidence interval (CI): 81.6-91.9%) after 5
      years. The most frequent complication was debonding (loss of retention), which
      occurred in 19.2% (95% CI: 13.8-26.3%) of RBBs over an observation period of 5
      years. The annual debonding rate for RBBs placed on posterior teeth (5.03%)
      tended to be higher than that for anterior-placed RBBs (3.05%). This difference,
      however, did not reach statistical significance (P=0.157). Biological
      complications, like caries on abutments and RBBs lost due to periodontitis,
      occurred in 1.5% of abutments and 2.1% of RBBs, respectively. CONCLUSION: Despite
      the high survival rate of RBBs, technical complications like debonding are
      frequent. This in turn means that a substantial amount of extra chair time may be
      needed following the incorporation of RBBs. There is thus an urgent need for
      studies with a follow-up time of 10 years or more, to evaluate the long-term
      outcomes.

PMID- 18070121
TI  - Fine needle aspiration cytology of an enlarged inguinal lymph node.

PMID- 18070122
TI  - Role of CD10 immunochemistry in differentiating hepatocellular carcinoma from
      metastatic carcinoma of the liver.
AB  - BACKGROUND: Differentiation of hepatocellular carcinoma (HCC) from metastatic
      carcinoma in liver may be difficult on fine needle aspiration cytology (FNAC),
      especially when both appear as moderate to poorly differentiated tumours. A panel
      of immunocytochemical stains is frequently used in case of diagnostic difficulty.
      Recently, CD10 immunostain with a canalicular staining pattern has been shown to
      be a specific marker for hepatocytic differentiation. OBJECTIVE: The present
      study was designed to assess the value of CD10 immunostain in distinguishing HCC
      from metastatic carcinoma in material obtained by FNAC of liver masses. MATERIALS
      AND METHODS: Formalin-fixed, paraffin-embedded cell blocks of 22 cases (7 cases
      of HCC and 15 cases of metastatic carcinoma), direct acetone-fixed smears and
      destained smears of 28 cases (18 cases of HCC and 10 cases of metastatic
      carcinoma) prepared from FNAC of the liver were immunostained using monoclonal
      antibody against CD10. RESULTS: Seventeen (68%) of twenty-five cases of HCC were
      positive for CD10 with a canalicular staining pattern. Among them 7 (70%) of 10
      cases were well-differentiated HCC and 10 (66%) of 15 cases were moderate to
      poorly differentiated HCC. Of 25 cases of metastatic carcinoma, four (16%) were
      positive for CD10 with a cytoplasmic (three cases) and membranous staining (one
      case) pattern. CONCLUSION: CD10 immunostaining is useful in discriminating HCC
      and metastatic carcinoma of the liver and is easily applied on cell blocks as
      well as FNAC smears.

PMID- 18070123
TI  - Reliability of isokinetic strength imbalance ratios measured using the Cybex NORM
      dynamometer.
AB  - The main aim of this study was to examine the absolute and relative reliability
      of some commonly used strength imbalance indices such as concentric hamstring-to
      concentric quadriceps ratio, eccentric hamstring-to-concentric quadriceps ratio
      and bilateral concentric and eccentric strength ratios. An additional aim was to
      examine the reliability of the peak torque and work of the knee extensor and
      flexor muscles measured using the Cybex NORM dynamometer. Eighteen physically
      active healthy subjects (mean +/- standard deviation, age 23 +/- 3 years, height
      176 +/- 5 cm, body mass 74 +/- 8 kg) were tested three times with 96 h between
      sessions. Peak torque, average work, unilateral and bilateral ratios were
      determined at 60, 120, 180 and -60 degrees s(-1). Low (0.34) to moderate (0.87)
      relative reliability (intraclass correlation coefficient, ICC) was found for
      strength imbalance ratios with eccentric hamstring-to-concentric quadriceps ratio
      showing the greater ICC (>0.80). High ICC values (0.90-0.98) were found for peak
      torque and average work. Absolute reliability (standard error of measurement)
      ranged from 3.2% to 8.7% for strength imbalance ratios and from 4.3% to 7.7% for
      peak torque and average work measurements. This study established the reliability
      of the most common strength imbalance ratios and of absolute isokinetic muscle
      strength assessed using the Cybex NORM.

PMID- 18070124
TI  - A technique for dating toxoplasmosis in pregnancy and comparison with the Vidas
      anti-toxoplasma IgG avidity test.
AB  - A comparative evaluation of 384 selected sera was performed using the Beckman
      Coulter Access and Abbott Axsym Toxo-IgG assays. The Axsym assay yields positive
      early results following infection, while the Access assay gives higher titres
      during chronic infection. The ratio between the two complementary tests, Axsym
      Toxo-IgG/Access Toxo-IgG (Ax/Ac), was compared with the Vidas anti-Toxoplasma IgG
      avidity index (AI). The Ax/Ac ratio decreased progressively as the time between
      infection and sampling increased. The mean Ax/Ac values (+/-SE) were 2.50 (+/
      0.26), 2.14 (+/-0.13), 2.33 (+/-0.22), 1.34 (+/-0.09), 1.32 (+/-0.10), 0.92 (+/
      0.08) and 0.74 (+/-0.07) for groups of sera sampled at 1, 2, 3, 4-5, 6-8, 9-12
      and 13-24 months, respectively, after infection in pregnant women. These values
      were much smaller for cases with chronic infection (>24 months), i.e., 0.56 (+/
      0.03), 0.44 (+/-0.04) and 0.53 (+/-0.04), respectively, for pregnant women and
      immunodepressed patients with and without reactivation. Taking a ratio of 1 as a
      threshold for recent infection, the patients in the groups sampled at 1, 2 and 3
      months had Ax/Ac ratios >1 in 49/50 (98%), 53/55 (96.4%) and 36/36 (100%) cases,
      respectively. Thus, an Ax/Ac ratio of <1 in serum from a pregnant woman allows a
      recent infection (<3 months) to be excluded. This technique has the advantage of
      yielding positive results that develop much more rapidly than the AI, thereby
      helping to reassure large numbers of pregnant women and avoiding costly and
      unnecessary prophylactic treatment and follow-up.

PMID- 18070125
TI  - Risk-factors for human infection with Orientia tsutsugamushi: a case-control
      study in Korea.
AB  - A case-control study was conducted involving 156 patients with scrub typhus and
      130 controls. Three factors were associated significantly with the risk of
      developing scrub typhus: engaging in fruit farming (OR 2.44; 95% CI 1.04-5.69),
      gathering chestnuts (OR 2.05; 95% CI 1.09-3.87) and taking breaks in areas
      adjacent to agricultural operations (OR 3.06; 95% CI 1.50-6.22). In contrast,
      receiving information or educational materials concerning the prevention of scrub
      typhus had a protective effect (OR 0.45; 95% CI 0.24-0.83). These results suggest
      that a health education programme will lower the risk of developing scrub typhus
      when applied to high-risk groups.

PMID- 18070126
TI  - Skeletal dysplasias and the growth plate.
AB  - Skeletal dysplasias are disorders in which there is derangement in the growth or
      shape of the skeleton. Long bone grows from cartilage that persists near the ends
      until skeletal maturity as the growth plate. Developmental biology work has
      identified the major regulatory proteins in growth plate chondroyte function.
      There are hundreds of skeletal dysplasias, and the molecular genetic etiology of
      many was defined in the past decade and a half. Now that the causative genes for
      these disorders have been identified, they can be broadly classified by the
      function of the protein that these genes encode for into disorders caused by
      extracellular structural proteins, proteins that regulate normal growth plate
      chondrocyte differentiation and patterning, and enzymes that process these
      proteins. There are clinical similarities within each group, and the phenotype
      can be predicted based on the role of the mutated protein in normal growth plate
      function. As such, this framework to classify the skeletal dysplasias has
      practical clinical implications.

PMID- 18070127
TI  - Use of multiplex ligation-dependent probe amplification increases the detection
      rate for 11p15 epigenetic alterations in Silver-Russell syndrome.
AB  - Silver-Russell syndrome (SRS) describes a malformation syndrome with severe
      intrauterine and postnatal growth retardation. Currently, two major
      (epi)mutations have been described: while approximately 10% of patients carry a
      maternal uniparental disomy of chromosome 7 (UPD7), 35-60% show a hypomethylation
      at the H19 differentially methylated regions (DMRs) in 11p15. Until recently, a
      Southern-blot based test was routinely used to identify epimutation carriers.
      Nevertheless, this test was time consuming and hampered by the huge amount of
      genomic DNA needed. With the methylation-specific multiplex ligation-dependent
      probe amplification assay (MLPA) for SRS, a PCR-based test is now available,
      allowing the analysis also of small amounts of DNA. Probes in this assay
      hybridize to the H19 DMRs but do not cover the genomic target of the Southern
      blot probe. We now screened 72 patients with SRS by MLPA. Hypomethylation of the
      H19 DMRs was confirmed in all patients analyzed by Southern blot. In addition, we
      identified six individuals with hypomethylation of the H19 DMR who had previously
      normal blot results. This discrepancy can be explained by the observed generally
      lower degree of demethylation in this group, possibly not detectable by the less
      sensitive Southern-blot method but also with a varying degree of methylation at
      different DMRs in the same individual. Apart from hypomethylation in the H19 DMR,
      we observed a slight demethylation for one of the IGF2 probes. The total
      detection rate of 11p15 hypomethylation is now increased to >38%. Considering
      maternal UPD7 and chromosomal aberrations, (epi)genetic alterations now account
      for more than 50% of SRS patients. In summary, MLPA represents an easy, low cost
      and reliable system in the molecular diagnostics of SRS.

PMID- 18070128
TI  - Polymorphisms spanning the 0N exon and promoter of the estrogen receptor-beta
      (ERbeta) gene ESR2 are associated with venous ulceration.
AB  - Venous ulcers are characterized by excessive inflammation and raised levels of
      proinflammatory cytokines. Estrogen has been shown to accelerate the rate of
      wound healing in elderly subjects by dampening the inflammatory response. The
      estrogen receptor (ER) proteins, ER-alpha (ERalpha) and ER-beta (ERbeta) mediate
      the actions of estrogen during wound repair through the activation or repression
      of target gene transcription. Recent evidence implicates the chromosomal region
      harboring the ERbeta gene with venous ulceration in a British Caucasian
      population, highlighting the need to conduct further genetic interrogation. To
      address this, we conducted a case-control study to investigate whether single
      nucleotide polymorphisms in the ERbeta gene are associated with venous ulceration
      in elderly (age >50 years) subjects. We recruited a case group (n = 124, 56 males
      and 68 females) consisting of patients with an active venous ulcer and a control
      group consisting of individuals from the general population with no evidence of
      venous disease or history of venous ulceration (n = 380, 189 males and 191
      females). Polymorphisms in close proximity to upstream regulatory regions of the
      ERbeta gene, including the 0N exon and promoter transcribed in inflammatory
      cells, were significantly (p < 0.05) associated with venous ulceration. A major
      susceptibility haplotype carried by 23% (26/112) of cases compared with only 10%
      (27/276) of controls (odds ratio = 2.8, 95% confidence interval = 1.6-5.0) was
      significantly (p < 0.01) associated with elevated serum levels of tumor necrosis
      factor-alpha. In conclusion, common variation in the regulatory regions of the
      ERbeta gene may pre-dispose to venous ulceration in a British Caucasian
      population.

PMID- 18070129
TI  - Detection of cytomegalovirus reactivation in cancer patients receiving
      chemotherapy.
AB  - While increasing numbers of cytomegalovirus (CMV)-associated diseases are
      occurring in patients undergoing conventional chemotherapy, information regarding
      CMV reactivation is limited. This pilot study was conducted to investigate CMV
      reactivation induced by chemotherapy. Seven blood samples were collected from
      each of 15 patients with newly diagnosed malignant disease, at baseline before
      chemotherapy, and once every month after chemotherapy was commenced. CMV viral
      loads in leukocytes were determined by real-time PCR. Host responses to changes
      in viral loads were assessed by assaying CMV-specific IgG titres and tumour
      necrosis factor (TNF)-alpha and interferon (IFN)-gamma levels in each of the
      blood samples, and by scoring the number of CMV-associated clinical symptoms that
      developed. All except one patient experienced CMV reactivation during the course
      of chemotherapy, with the average viral load peaking after the third course of
      treatment. Titres of CMV-specific IgG increased in line with the increase in
      viral load. Plasma levels of TNF-alpha and IFN-gamma initially decreased from
      baseline, and then rose to peak levels at the same time as, or shortly after, the
      highest viral loads were recorded. Clinical symptoms potentially attributable to
      CMV infection appeared as the viral load increased. It was concluded that the
      incidence of CMV reactivation in patients receiving conventional chemotherapy is
      high. Reactivation is not asymptomatic, but was self-limiting in most of these
      cases. Increases in plasma TNF-alpha and IFN-gamma occur after reactivation, but
      not before.

PMID- 18070130
TI  - EUCAST technical note on fluconazole.

PMID- 18070131
TI  - Acute Chlamydia pneumoniae infections in asthmatic and non-asthmatic military
      conscripts during a non-epidemic period.
AB  - Chlamydia pneumoniae respiratory tract infections were studied in 512 male
      military conscripts (123 asthmatic and 389 non-asthmatic) taking part in 180-day
      service between July 2004 and July 2005 in Kajaani, Finland. Respiratory tract
      infections requiring a medical consultation were analysed prospectively. At
      baseline, at end of service, and during each episode of respiratory infection,
      blood samples were obtained for measurement of C. pneumoniae antibodies. Data
      concerning the clinical features of each infection episode were collected.
      Serological evidence of acute C. pneumoniae infection was found in 34 of the 512
      conscripts with antibody data available, including 9.8% of the asthmatic subjects
      and 5.7% of the non-asthmatic subjects (p 0.111). A serological diagnosis could
      be made for 25 clinical episodes in 24 conscripts. The spectrum of respiratory
      tract infections included 13 episodes of mild upper respiratory tract infection
      and seven episodes of sinusitis, with five episodes involving asthma
      exacerbation. Two of three pneumonias were primary infections. Primary infections
      were diagnosed in five subjects, and re-infection/reactivation in 19 subjects,
      with the latter comprising 12 non-asthmatic subjects and seven asthmatic subjects
      (p 0.180). Prolonged infections were present in six asthmatic subjects and one
      non-asthmatic subject (p 0.001). A wide variety of respiratory tract infections,
      ranging from common cold to pneumonia, were associated with serologically
      confirmed C. pneumoniae infections. Infections were often mild, with common cold
      and sinusitis being the most common manifestations. Acute, rapidly resolved C.
      pneumoniae infections were equally common among asthmatic subjects and non
      asthmatic subjects, whereas prolonged infections were more common among subjects
      with asthma.

PMID- 18070132
TI  - Rapid culture and identification: a practical method for early preliminary
      laboratory diagnosis of sepsis.
AB  - This study describes the development of a method for rapid preliminary species
      identification of bacteria from positive blood culture vials. The method yielded
      preliminary identification results for 496 (92%) of 541 positive blood cultures
      within 5 h. The method was capable of identifying the most frequently isolated
      bacteria (i.e., Staphylococcus aureus, coagulase-negative staphylococci,
      Escherichia coli, Streptococcus pneumoniae and Enterococcus spp.) to the species
      level. The method can be established easily, with a materials cost of 2-5 Euros
      per sample.

PMID- 18070133
TI  - MRSA in Austria--an overview.
AB  - The aim of this study was to provide an overview of predominant and sporadic
      methicillin-resistant Staphylococcus aureus (MRSA) strains in large regions of
      Austria, and to compare the results with those from other European countries. In
      total, 1439 MRSA isolates, collected routinely between January 1996 and June 2006
      from five Austrian federal provinces, were investigated. The isolates were
      confirmed as MRSA using mecA/femA multiplex PCR assays. Genes encoding Panton
      Valentine leukocidin (PVL), which are characteristic of community-acquired MRSA,
      were also detected by PCR. Subtyping was performed using SmaI macrorestriction
      digestion of genomic DNA, followed by pulsed-field gel electrophoresis (PFGE) and
      cluster analysis. Isolates that could not be assigned to clusters were further
      analysed by spa typing and/or multilocus sequence typing. The predominant clones
      detected in Austria were ST228 (southern German epidemic clone), ST5 (Rhine
      Hessen MRSA), the ST8 Austrian clone and CC8/ST8. Whereas the frequencies of
      lineages corresponding to ST247, ST45 and ST22 remained comparably low, an
      increase in the frequency of lineages corresponding to ST5 and to ST228 was
      recorded. Overall, 20 different MRSA types and 321 subtypes were recognised
      according to PFGE analysis. The prevalence of different strains varied
      considerably in the different Austrian regions. When compared to other European
      countries, the situation in Austria was most similar to that found in Germany.

PMID- 18070134
TI  - Identification of a novel TGFBR1 mutation in a Loeys-Dietz syndrome type II
      patient with vascular Ehlers-Danlos syndrome phenotype.

PMID- 18070135
TI  - Perinatal lethal Gaucher's disease without prenatal complications.

PMID- 18070136
TI  - Restless legs syndrome: an update on genetics and future perspectives.
AB  - Restless legs syndrome (RLS) is a common, underdiagnosed neurological condition
      with an age-dependent prevalence of up to 14%. Familial aggregation has been
      widely shown since Ekbom's first description of the disorder in 1945. Five loci
      (12q, 14q, 9p, 2q, and 20p) have been described so far, although no positive
      association with any specific genes, either within these loci or additional
      candidates investigated, has been reported. Two recent genome-wide association
      studies have reported positive association with sequence variants in or around
      specific genes on chromosomes 6p, 2p and 15q. The molecular findings, together
      with the variable expressivity of the phenotype, suggest a substantial clinical
      and genetic heterogeneity of RLS. This article reviews the clinical
      characteristics, diagnosis and epidemiology with a focus on the genetics and
      pathogenesis of RLS.

PMID- 18070137
TI  - Homozygosity for mutation G212A of the gene for aspartoacylase is associated with
      atypical form of Canavan's disease.

PMID- 18070138
TI  - Restoring reproductive confidence in families with X-linked mental retardation by
      finding the causal mutation.

PMID- 18070139
TI  - When adaptive processes go awry: gain-of-function in SCN9A.

PMID- 18070140
TI  - A life without pain? Hedonists take note.

PMID- 18070142
TI  - Efficacy of nitroglycerine infusion versus sublingual nifedipine in severe pre
      eclampsia: a randomized, triple-blind, controlled trial.
AB  - 1. Information regarding the use of continuous i.v. administration of
      nitroglycerine as an antihypertensive agent in the management of pre-eclampsia is
      scarce. In the present study, i.v. nitroglycerine or sublingual nifedipine were
      administered to 32 women with severe pre-eclampsia who were being managed with
      controlled plasma volume expansion and MgSO(4) loading and maintenance doses.
      Maternal blood pressure and heart rate responses, fetal heart rate responses and
      perinatal fetal-maternal adverse effects were evaluated using classical
      parametric and non-parametric data analysis and data modelling by mixed models.
      2. An important hypotensive response was observed in both groups, although this
      reponse was greater, faster and exhibited less variability (more precision) in
      the nitroglycerine-treated group. Heart rate also increased in both the
      nitroglycerine- and nifedipine-treated groups (4.6 +/- 4.4 vs 8.6 +/- 5.3 b.p.m.,
      respectively), although the increase in the nifedipine-treated group was almost
      twofold that in the nitroglycerine-treated group. There were no significant
      changes in fetal heart rate in response to vasodilator therapy. The frequency of
      perinatal fetal-maternal adverse effects was similar in both groups at 40% and
      the adverse effects observed included flushing, headache, palpitations and
      nausea. 3. In conclusion, i.v. infusion of nitroglycerine is an effective, safe
      and alternative therapy for severe pre-eclampsia.

PMID- 18070141
TI  - Sex differences in response to cyclosporine immunosuppression in experimental
      kidney transplantation.
AB  - 1. Female donors and recipients have increased risk of acute rejection and
      subsequent chronic allograft nephropathy (CAN), especially when cyclosporine A
      (CsA) is used. Decreased renal nitric oxide (NO) production is associated with
      chronic kidney disease. In the present study, we investigated the impact of
      gender, CsA dose and renal NO synthase (NOS) on CAN. 2. Kidneys from male and
      female F344 rats were transplanted into same-sex Lewis allograft or F344 isograft
      recipients and recipient rats were treated with 1.5 or 3 mg/kg per day CsA for 10
      days. Grafts were removed at 22 weeks post-transplantation. Normal two-kidney
      F344 rats were investigated as age-matched controls. 3. Low-dose CsA was
      associated with accelerated CAN in female rats compared with male rats; however,
      with high-dose CsA, allograft females had similar pathology/function to allograft
      males. Isograft females (similar to isograft males) had no graft failure and only
      slightly, albeit significantly, greater injury than age-matched controls.
      Isograft females had higher renal cortical neuronal (n) NOS but lower medullary
      endothelial (e) NOS than isograft males. There was no difference in renal eNOS
      and nNOS between allograft groups. 4. In conclusion, 1.5 mg/kg per day CsA is not
      sufficient to prevent early graft loss in females. When the dose of CsA is
      doubled, allograft females and males have similar post-transplant survival. Renal
      NOS expression was unremarkable in any transplant group.

PMID- 18070143
TI  - Evaluation of adrenal function using the human corticotrophin-releasing hormone
      test, low dose Synacthen test and 9am cortisol level in children and adolescents
      with central adrenal insufficiency.
AB  - BACKGROUND: The insulin tolerance test (ITT) has become less popular in
      paediatrics because of the risks associated with hypoglycaemia. Human
      corticotrophin-releasing hormone (hCRH) test results correlate with the ITT and
      may be an acceptable method to test for central adrenal insufficiency (CAI).
      Simpler tests, such as the low dose Synacthen test (LDST) and 9am cortisol, have
      also been proposed. OBJECTIVE: To compare the ability of the hCRH test, LDST, 9am
      cortisol level and 24-h cortisol profiles to diagnose CAI in a paediatric
      population. DESIGN AND SETTING: A cross-sectional study in a tertiary paediatric
      endocrine clinic. PARTICIPANTS: Thirty-one children and adolescents (aged 2.3
      18.3 years) with CAI risk factors had an hCRH test, LDST, 9am cortisol and 24-h
      cortisol profile performed. RESULTS: Of 23 patients with confirmed CAI (hCRH peak
      cortisol < 400 nmol/), 19 failed the LDST (peak cortisol < 267 nmol/l, i.e. 10th
      percentile for controls). Nineteen would have failed based on the 10th percentile
      cut point for 9am cortisol (< 140 nmol/l). Using receiver operating
      characteristic (ROC) curve coordinates, a 9am cortisol < 108 nmol/l was sensitive
      (83%) and specific (99%) for CAI. The 9am cortisol levels measured on two
      occasions were repeatable (94%) and correlated (r = 0.83, P = 0.01). All eight
      adrenally sufficient patients (hCRH peak cortisol > or = 400 nmol/l) passed the
      LDST. Seven had normal 9am cortisol (> or = 140 nmol/l). The 24-h cortisol area
      under the curve (AUC) for these patients was within the 10th-90th percentiles for
      control subjects' AUC. The peak cortisol to hCRH and LDST were correlated (r =
      0.88, P = 0.01), with no difference between the peaks (mean difference -5.3
      nmol/l, P = 0.69). CONCLUSIONS: In children with CAI risk factors, the diagnosis
      can be made if unstressed 9am cortisol is < 108 nmol/l. As cortisol levels > 381
      nmol/l are highly suggestive of normal hypothalamic-pituitary-adrenal (HPA)
      function, stimulation testing need only be performed if 9am cortisol is 108-381
      nmol/l. The LDST should be interpreted cautiously because mild CAI may be missed.
      When stimulation results are marginal, 24-h cortisol profiles can provide
      reassurance of normal cortisol status.

PMID- 18070144
TI  - The antioxidant alpha-lipoic acid improves endothelial dysfunction induced by
      acute hyperglycaemia during OGTT in impaired glucose tolerance.
AB  - OBJECTIVE: Impaired glucose tolerance (IGT) is considered a transitional phase in
      the development of type 2 diabetes, and is also independently associated with the
      occurrence of cardiovascular disease. Endothelial dysfunction (ED) represents a
      very early step in the development of atherosclerosis. The aim of the present
      study was to examine ED in the fasting state and after a glucose challenge as
      well as after administration of an antioxidant agent. PATIENTS AND METHODS: The
      study subjects included 42 IGT patients and 26 healthy individuals (control
      group). The IGT patients were randomly divided into two groups, 21 in each group
      (the alpha-lipoic acid group and the placebo group). In the alpha-lipoic acid
      group, 300 mg of alpha-lipoic acid was administrated before an oral glucose
      tolerance test (OGTT); in the placebo group, 250 ml of 0.9% sodium chloride was
      administrated before the OGTT. In addition, 250 ml of 0.9% sodium chloride was
      also administrated to the control subjects before the OGTT (control group), and
      then vascular function was examined in the fasting state and repeated 1 and 2 h
      after the glucose load. High-resolution ultrasound was used to measure flow
      mediated endothelium-dependent arterial dilation (FMD) and glyceryltrinitrate
      (GTN)-induced endothelium-independent arterial dilation. RESULTS: In the fasting
      state, and at 60 and 120 min, FMD in both the placebo and alpha-lipoic acid
      groups was significantly lower than in the controls (P < 0.01). In the control
      group, FMD tended to decrease at 60 min after glucose loading and returned to the
      baseline levels at 120 min (P > 0.05). In the placebo group, FMD decreased
      significantly at 60 min after glucose loading (P < 0.01) and increased markedly
      from 60 to 120 min (P < 0.01). The alpha-lipoic acid-treated patients showed FMD
      values intermediate between the control subjects and the IGT patients treated
      with placebo, at both 60 and 120 min, and the differences were significant (P <
      0.01). In multiple regression analysis, FMD was significantly correlated to
      fasting blood glucose (FBG), low density lipoprotein cholesterol (LDL-C),
      lipoprotein (a) [Lp(a)], C-reactive protein (CRP), thiobarbituric acid reactive
      substances (TBARS) and age in IGT patients at baseline (P < 0.01). Spearman's
      analysis showed a significant negative correlation between FMD and plasma glucose
      levels, and between FMD and TBARS during the OGTT in IGT patients (placebo group)
      (P < 0.01). There was also a significant correlation between FMD and plasma
      glucose levels, and between FMD and TBARS during the OGTT in IGT patients treated
      with alpha-lipoic acid (P < 0.05), although the power of association decreased.
      CONCLUSION: In subjects with IGT, FMD was impaired both in the fasting state and
      after a glucose challenge, probably through increased production of oxygen
      derived free radicals. The ED observed after a glucose challenge is related to
      the extent of hyperglycaemia and TBARS, and an antioxidant agent can improve the
      impairment of endothelial function induced by acute hyperglycaemia.

PMID- 18070145
TI  - Expression of pituitary tumour-derived, N-terminally truncated isoform of
      fibroblast growth factor receptor 4 (ptd-FGFR4) correlates with tumour
      invasiveness but not with G-protein alpha subunit (gsp) mutation in human GH
      secreting pituitary adenomas.
AB  - OBJECTIVE: Apart from the constitutively activating mutation of the G-protein
      alpha subunit (Gsalpha) (gsp mutation), factors involved in tumorigenesis or
      those in tumour behaviour remain elusive in sporadic GH-secreting pituitary
      adenomas. Recently, the N-terminally truncated form of fibroblast growth factor
      receptor-4 (ptd-FGFR4) was identified in pituitary adenomas. This aberrant
      receptor has transforming activity, and causes pituitary adenomas in transgenic
      mice. The clinical relevance of this receptor warrants investigation. Our
      objective was twofold: first, to examine how the expression of ptd-FGFR4 relates
      to gsp mutations; and second, to see whether patients with this receptor have
      unique clinical characteristics. MATERIALS AND METHODS: mRNA was extracted from
      excised adenomas of 45 Japanese acromegalic patients. ptd-FGFR4 expression and
      gsp mutations were determined by reverse transcription polymerase chain reaction
      (RT-PCR) and direct sequencing. Preoperative clinical data were collected by
      reviewing medical charts and pituitary magnetic resonance imaging (MRI) scans.
      RESULTS: ptd-FGFR4 mRNA expression was detected in 19 out of 45 tumours (42.2%)
      while gsp mutations were detected in 25 out of 45 tumours (55.6%). The prevalence
      of ptd-FGFR4 expression did not differ between gsp-positive (44.0%) and gsp
      negative (40.0%) tumours (P = 1.00). ptd-FGFR4-positive tumours invaded the
      cavernous sinus more frequently (P = 0.0098) than did the ptd-FGFR4-negative
      tumours. Tumour size was not statistically different between ptd-FGFR4-positive
      and -negative tumours (P = 0.198). The presence of ptd-FGFR4 did not correlate
      with age at operation, sex, preoperative serum GH or IGF-1 levels. CONCLUSIONS:
      We found that ptd-FGFR4 expression and gsp mutations occur independently of each
      other, and that ptd-FGFR4 expression is associated with more invasive tumours in
      patients with GH-secreting pituitary adenomas.

PMID- 18070147
TI  - BRAF mutation associated with other genetic events identifies a subset of
      aggressive papillary thyroid carcinoma.
AB  - PURPOSE: BRAF(V600E) mutation represents the most common oncogenic event in
      sporadic papillary thyroid cancer (PTC). There are, however, significant
      discrepancies regarding the overall frequency, its prevalence in PTC-variants,
      and its relationship with clinico-pathological parameters of poor outcome.
      Moreover, the impact of BRAF(V600E) mutants on tumour-related patient's death has
      not been evaluated. DESIGN: We analysed, by PCR-SSCP and/or PCR-direct
      sequencing, exons 8, 10, 11 and 15 of BRAF in 113 tumour samples from 49 PTC
      patients. Matched lymph node metastases and/or distant metastases (DMs) were
      screened in 35 patients. Focal changes in the growth pattern or microscopic grade
      within the primary tumour (Pt) or the metastases were separately genotyped.
      Mutations at H-, K-, N-ras and PIK3CA exons 9 and 20 were also investigated. For
      comparison with PTC cases, the BRAF and Ras mutational status was evaluated in 89
      specimens obtained from 24 poorly differentiated thyroid carcinomas (PDCs) and 36
      anaplastic thyroid carcinomas (ATCs). RESULTS: BRAF(V600E) was found in 13/16
      classical PTCs (CL-PTCs), 6/17 follicular variant PTCs (FV-PTCs) and 8/16 mixed
      (papillary/follicular) PTCs (Mx-PTCs), being significantly associated with CL
      PTCs (P = 0.015). BRAF(V600E) segregated with metastatic PTC-cells in 43% of the
      patients, but only one DM disclosed the mutation. PTC-tumours featuring
      concurrent less-differentiated foci were BRAF wild-type in both components.
      Noteworthy, the frequency of BRAF mutations among PDCs and ATCs resulted
      considerably lower (16.6% and 25%, respectively) than in PTCs (55%). The
      prevalence of Ras mutations among PDCs and ATCs (46% and 36%, respectively) was,
      however, much higher than in PTCs (14%). Five (71%) of the patients who died of
      PTC displayed somatic mutations. Four of them had other gene alteration
      associated with BRAF(V600E) and the only one that did not, BRAF(V600E) was
      restricted to the Pt. The occurrence of BRAF(V600E) associated with other genetic
      events was an independent predictor of DMs during follow-up, recurrence and
      tumour-related death. Remarkably, two PDCs (8.3%) and five ATCs (14%) revealed
      concurrent BRAF and Ras mutations. CONCLUSION: BRAF(V600E)'alone' does not
      represent a marker for poor outcome, however, when associated with alterations in
      other genes identifies a subset of PTCs with increased risk of recurrence and
      decreased survival.

PMID- 18070148
TI  - Translational mini-review series on complement factor H: therapies of renal
      diseases associated with complement factor H abnormalities: atypical haemolytic
      uraemic syndrome and membranoproliferative glomerulonephritis.
AB  - Genetic and acquired abnormalities in complement factor H (CFH) have been
      associated with two different human renal diseases: haemolytic uraemic syndrome
      and membrano proliferative glomerulonephritis. The new genetic and pathogenetic
      findings in these diseases and their clinical implications for the management and
      cure of patients are reviewed in this paper.

PMID- 18070149
TI  - Treatment with glutamine is associated with down-regulation of Toll-like receptor
      4 and myeloid differentiation factor 88 expression and decrease in intestinal
      mucosal injury caused by lipopolysaccharide endotoxaemia in a rat.
AB  - Recent evidence suggests that lipopolysaccharide (LPS) endotoxaemia in a rat
      causes significant mucosal injury. Our objective was to determine the effects of
      glutamine (Gln) on Toll-like receptor 4 (TLR-4), myeloid differentiation factor
      88 (Myd88) and tumour necrosis factor (TNF)-alpha receptor-associated factor 6
      (TRAF6) expression in intestinal mucosa following LPS endotoxaemia in a rat. For
      this purpose, male Sprague-Dawley rats were assigned randomly to one of three
      experimental groups of 10 rats each: (i) control rats underwent intraperitoneal
      (i.p.) injection of sterile saline once a day; (ii) rats were treated with LPS
      given i.p. once a day at a dose of 10 mg/kg for 48 h (two doses); and (iii) rats
      were pretreated with oral Gln given in drinking water (2%) 48 h before and
      following injection of LPS. Intestinal mucosal parameters, enterocyte
      proliferation and apoptosis were determined at death. TLR-4 and MyD88 mRNA
      expression was measured with reverse transcription-polymerase chain reaction (RT
      PCR). TLR-4 and MyD88 protein expression were analysed by Western immunoblotting.
      We observed a statistically significant (P < 0.05) decrease in mucosal weight,
      mucosal DNA and enterocyte proliferation and a significant increase in enterocyte
      apoptosis in rat intestine, following LPS administration. These changes were
      attenuated significantly by dietary Gln. Expression of TLR-4, MyD88 and TRAF6
      mRNA in the mucosal ileum was significantly higher in LPS rats versus control
      rats (P = 0.0006, P = 0.0015, P = 0.03, respectively) as well as TLR-4 and MyD88
      protein expression. The administration of Gln reduced significantly the
      expression of TLR-4, MyD88 and TRAF6 (P = 0.023, P = 0.014, P = 0.035,
      respectively) mRNA as well as TLR-4 and MyD88 protein expression in ileum
      compared to LPS animals. We did not find a significant change in the expression
      of TLR-4, MyD88 or TRAF6 in the jejunum of different groups. We conclude that
      treatment with Gln was associated with down-regulation of TLR-4, MyD88 and TRAF6
      expression and concomitant decrease in intestinal mucosal injury caused by LPS
      endotoxaemia in a rat.

PMID- 18070150
TI  - T cell activation profiles in Kawasaki syndrome.
AB  - Superantigens (SAgs) are potent stimulators of T cells bearing specific Vbeta T
      cell receptors (TCR) and may play a role in the pathogenesis of Kawasaki syndrome
      (KS), although despite 15 years of intense study this area remains controversial.
      Because SAgs can cause Vbeta restricted T cell activation in the absence of Vbeta
      skewing the aims of this study were to describe a flow cytometric protocol to
      study both CD4 and CD8 Vbeta repertoires, and CD69 expression across the CD4 and
      CD8 Vbeta repertoire in children with KS. Sixteen children with KS were studied.
      There was no significant increase in overall peripheral blood CD4 or CD8 T cell
      activation as determined by CD69 expression. However, Vbeta restricted CD4 and/or
      CD8 activation was observed in eight of 11 (72%) of the KS patients, a finding
      not observed in healthy controls. Thirteen of 16 (81%) of the KS patients had
      evidence of either Vbeta skewing (particularly CD4 Vbeta2 and Vbeta5.1) and/or
      Vbeta restricted activation. Three patients had Vbeta restricted activation in
      the absence of skewing. We suggest that these preliminary observations highlight
      the many layers of complexity when considering T cell activation in KS, which
      could explain some of the conflicting studies regarding peripheral blood T cell
      activation and Vbeta skewing. It is likely that in order to move forward with
      this debate a combination of detailed microbiological, immunological and
      molecular techniques applied to individual patients will be required ultimately
      to prove or refute the SAg hypothesis of KS.

PMID- 18070151
TI  - High serum YKL-40 level in a cohort of octogenarians is associated with increased
      risk of all-cause mortality.
AB  - YKL-40 is secreted by macrophages, neutrophils, chondrocytes, endothelial-,
      vascular smooth muscle- and cancer cells. Interleukin (IL)-6 stimulates YKL-40
      production in human in vivo studies. High serum YKL-40 is associated with poor
      prognosis in patients with inflammatory diseases and cancer. We studied whether
      serum YKL-40 was associated with systemic low-level inflammation, an immune risk
      phenotype, and mortality in relatively healthy 80-year old humans. Serum YKL-40,
      IL-6 and tumour necrosis factor (TNF)-alpha were measured by enzyme-linked
      immunosorbent assays (ELISAs) in octogenarians (n = 151) and serum YKL-40 in 18
      30-year-olds (n = 89). Fifty-one of the octogenarians died during the 6-year
      follow-up. Serum YKL-40 in octogenarians was higher compared to the level in
      young people (median 116 versus 31 microg/l, P < 0.0005). Serum YKL-40 correlated
      with serum IL-6 in elderly women (Spearman's rho = 0.30, P = 0.009) and men (rho
      = 0.25, P = 0.003), but only with serum TNF-alpha (rho = 0.23, P = 0.05) and C
      reactive protein (CRP) (rho = 0.57, P < 0.0005) among the elderly women. In
      addition, high serum level of YKL-40 was associated with a low CD4 : CD8 cell
      ratio. Univariate analysis of serum YKL-40 (logarithmically transformed and
      divided by tertiles) showed significant association with all-cause mortality
      [tertile 3: hazard ratio (HR) = 2.38, 95% confidence interval (CI): 1.19-4.78, P
      = 0.02]. The effect persisted after adjusting for potential confounders (sex,
      smoking, body mass index, chronic disease and anti-inflammatory medicine). These
      results suggest that serum YKL-40 is a prognostic and sensitive biomarker of all
      cause mortality in octogenarians.

PMID- 18070152
TI  - Dietary allergenic proteins and intestinal immunity: a shift from oral tolerance
      to sensitization.

PMID- 18070153
TI  - Correlation between immune and neuronal parameters and stress perception in
      allergic asthmatics.
AB  - BACKGROUND: Asthma is a chronic disease defined by airway inflammation, increased
      airway hyperresponsiveness and episodes of airway obstruction. Although there are
      abundant clinical and experimental data showing that stress may worsen asthma,
      the mechanisms linking stress to asthma are not well understood. By inducing a
      pro-inflammatory cytokine milieu, stress might enhance airway inflammation in
      bronchial asthma. We therefore investigated the correlation of stress perception
      and the cytokine profile of circulating lymphocytes in humans. METHODS: Allergic
      asthmatic patients and healthy controls were evaluated for perceived level of
      stress, demographic and lung function data. Whole blood cells were obtained and
      stimulated by mitogen to assess intracellular IL-4, IFN-gamma and TNF-alpha by
      flow cytometry. Neurotrophins nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF) were measured in serum. RESULTS: Asthmatic patients
      showed significantly higher percentages of TNF-alpha-producing T cells than
      healthy controls. Only in asthmatic patients was stress perception correlated
      with percentages of TNF-alpha-producing T cells and serum BDNF levels, while
      forced expiratory volume in 1 s (% predicted) was negatively correlated to BDNF.
      CONCLUSION: The results of our study support the hypothesis that stress
      deteriorates bronchial asthma by inducing a pro-inflammatory cytokine profile in
      allergic asthmatics. Stress management might provide a supplement therapy of
      allergic asthma.

PMID- 18070154
TI  - The influence of processing factors and non-atopy-related maternal and neonate
      characteristics on yield and cytokine responses of cord blood mononuclear cells.
AB  - RATIONALE: Several studies have evaluated the associations between cord blood
      cellular responses and atopic diseases in children, but the results of these
      studies are inconsistent. Variations in blood processing factors and maternal and
      infant characteristics are typically not accounted for and may contribute to
      these inconsistencies. METHODS: Cord blood samples were obtained from 287
      subjects participating in the Childhood Origins of ASThma project, a prospective
      study of children at high risk for the development of asthma/allergies.
      Mononuclear cells were stimulated with phytohaemagglutinin (PHA), phorbal
      myristate acetate/ionomycin or a suspension of killed staphylococcus, and IFN
      gamma, IL-10 and IL-13 were quantitated by ELISA. Cell yields and cytokine
      production were related to processing factors and maternal and infant
      characteristics. RESULTS: The strongest relationships between independent
      variables and cell yield or cytokine responses occurred with the season of birth.
      The highest median cell yields were seen in fall, and the lowest in summer
      (difference of 47%, P=0.0027). Furthermore, PHA-induced IL-5 and IL-13 responses
      were approximately 50% higher in spring and summer than in fall or winter
      (P<0.0001). Clots in the cord blood samples were associated with a reduced median
      cell yield (42% reduction, P<0.0001), and an increased PHA-induced IL-10
      secretion (27% increase, P=0.004). CONCLUSIONS: These data suggest that season of
      collection, and to a lesser extent clotting in samples, affect cord blood
      mononuclear cell yield and cytokine responses. Careful documentation and analysis
      of processing and environmental variables are important in understanding
      biological relationships with cytokine responses, and also lead to greater
      comparability among studies using these techniques.

PMID- 18070155
TI  - Sentinel lymph node as a target of molecular diagnosis of lymphatic
      micrometastasis and local immunoresponse to malignant cells.
AB  - The sentinel lymph node (SLN) is defined as the lymph node(s) first receiving
      lymphatic drainage from the site of the primary tumor. The histopathological
      status of SLN is one of the most significant predictors of recurrence and overall
      survival for most clinical stage I/II solid tumors. Recent progress in molecular
      techniques has demonstrated the presence of micrometastatic tumor cells in SLN.
      There is now a growing body of data to support the clinical relevance of SLN
      micrometastasis in a variety of solid tumors. Increasing the sensitivity of
      occult tumor cell detection in the SLN, using molecular-based analysis, should
      enable a more accurate understanding of the clinical significance of various
      patterns of micrometastatic nodal disease. The establishment of metastasis to SLN
      might not be simply reflected by the flow dynamics of lymphatic fluid that drains
      from the primary site to the SLN, and the transportation of viable cancer cells.
      Recent studies have demonstrated that primary tumors can actively induce
      lymphangiogenesis and promote SLN metastasis. Moreover chemokine receptors in
      tumor cells may facilitate organ-specific tumor metastasis in many human cancers
      and some experimental models. In contrast, recent clinical and preclinical
      studies regard SLN as the first lymphoid organ to respond to tumor antigenic
      stimulation. SLN dramatically show morphological, phenotypical and functional
      changes that indicate immune suppression by tumor cells. The immune suppression
      in SLN results in failure of prevention or eradication of tumor metastasis. The
      mechanism of immunomodulation remains unclear; however, several regulatory
      molecules produced by tumor cells and tumor-associated macrophages or lymphocytes
      are likely to be responsible for inducing the immune suppression in SLN. Further
      studies may develop a novel immunotherapy that overcomes tumor-induced immune
      suppression and can prevent or eradicate SLN metastasis.

PMID- 18070156
TI  - Effects of Cholerella sp. microalgae extract on colonic anastomosis in rats with
      protein-energy malnutrition.
AB  - OBJECTIVE: Algae, which are used as supplementary nutrients in various countries,
      are products rich in protein, vitamins and minerals. The aim of this study was to
      investigate the effects of algae extracts on the healing of colonic anastomosis
      in malnourished rats. METHOD: Seventy-two rats were randomized to three groups.
      Group 1 was fed with standard diet for 15 days, before and after the colonic
      anastomosis. Groups 2 and 3 were fed with a malnutrition diet for 15 days prior
      to colonic anastomosis and then with the basic diet for 15 days there after.
      Group 3 also received an extract of algae derived from Cholerella sp. via oral
      gavage postoperatively, in addition to the basic diet. Rats were killed on the
      3rd, 7th and 15th postoperative day. Blood samples were collected to evaluate
      prealbumin, transferring and albumin levels. Anastomotic bursting pressures
      (BPs), histopathology and tissue hydroxyproline levels were evaluated after
      killing. RESULTS: In group 3, the prealbumin level on the 3rd postoperative day
      and transferrin and albumin levels on the 7th and 15th postoperative days were
      significantly increased compared with the other groups (P < 0.05). Tissue
      hydroxyproline levels and anastomotic BPs of group 3 were significantly higher
      than in group 2 on the 3rd, 7th and 15th postoperative days (P < 0.05).
      Histopathological examination of the anastomosis revealed significantly better
      healing patterns for group 3 than for groups 1 and 2 (P < 0.05). CONCLUSION:
      Extract derived from Cholerella sp. microalgae has favourable effects on healing
      of experimental colon anastomoses.

PMID- 18070157
TI  - Glutamine preferentially inhibits T-helper type 2 cell-mediated airway
      inflammation and late airway hyperresponsiveness through the inhibition of
      cytosolic phospholipase A(2) activity in a murine asthma model.
AB  - BACKGROUND: The non-essential amino acid, l-glutamine (Gln), is abundant in the
      human body. Gln exhibits beneficial effects on endotoxic shock through the
      inhibition of cytosolic phospholipase A(2) (cPLA(2)) activity. cPLA(2) has been
      reported to be implicated in the pathogenesis of asthma, but the effects of Gln
      on asthma have not yet been defined. OBJECTIVE: To investigate the effects of Gln
      on allergic bronchial inflammation and airway hyperresponsiveness (AHR), and to
      determine the possible action mechanisms of Gln in a murine model of asthma.
      METHODS: cPLA(2) phosphorylation was assessed by immunoprecipitation and Western
      blotting. Smears of bronchoalveolar lavage cells were stained with Diff-Quik
      solution for differential cell counting. Airway levels of the proteins [T-helper
      type-1 (Th1) and Th2 cytokines, and mucin] were measured by ELISA. mRNA
      expression of cytokines was assessed by real-time RT-PCR. AHR was assessed as a
      change in airway resistance (RL). Histological studies were performed to assess
      the levels of mucin and pulmonary inflammation. RESULTS: Systemic Gln
      administration inhibited cPLA(2) phosphorylation and its enzymatic activity in
      the lungs. Additionally, Gln effectively suppressed the key features of Th2
      dependent asthmatic features, such as airway eosinophilia, mucus formation, and
      airway type 2 cytokine production, as well as late AHR. CONCLUSION: Gln was found
      to be effective in the suppression of Th2-dependent phenotypes and late AHR, and
      this effect of Gln appeared to be at least partially attributable to its ability
      to suppress cLPA(2) activity in the airway. Our results suggest that clinical use
      of Gln for patients with asthma may be beneficial.

PMID- 18070158
TI  - Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not
      acute physiological responses to allergen inhalation.
AB  - BACKGROUND: Asthma is a chronic inflammatory disease that is characterized
      clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The
      physiological response of the asthmatic lung to inhaled allergen is often
      characterized by two distinct phases: an early-phase response (EPR) within the
      first hour following exposure that subsides and a late-phase response (LPR) that
      is more prolonged and may occur several hours later. Mouse models of asthma have
      become increasingly popular and should be designed to exhibit an EPR, LPR and
      AHR. OBJECTIVE: To determine whether a common model of asthma is capable of
      demonstrating an EPR, LPR and AHR. METHODS: BALB/c mice were sensitized to
      ovalbumin (OVA) and challenged with one or three OVA aerosols. Changes in lung
      mechanics in response to allergen inhalation were assessed using a modification
      of the low-frequency forced oscillation technique (LFOT). In order to assess AHR,
      changes in lung mechanics in response to aerosolized methacholine were assessed
      using LFOT. Inflammatory cell infiltration into the lung was measured via
      bronchoalveolar lavage (BAL). ELISAs were used to measure inflammatory cytokines
      in the BAL and levels of IgE in the serum. RESULTS: An EPR was only detectable
      after three OVA aerosols in approximately half of the mice studied. There was no
      evidence of an LPR despite a clear increase in cellular infiltration 6 h post
      allergen challenge. AHR was present after a single OVA aerosol but not after
      three OVA aerosols. CONCLUSIONS: The lack of an LPR, limited EPR and the absence
      of a link between the LPR and AHR highlight the limitations of this mouse model
      as a complete model of the lung dysfunction associated with asthma.

PMID- 18070159
TI  - The association between mother and child MTHFR C677T polymorphisms, dietary
      folate intake and childhood atopy in a population-based, longitudinal birth
      cohort.
AB  - BACKGROUND: A recent study suggested a link between folate metabolism and atopy,
      based on a positive association between a common polymorphism of the
      methylenetetrahydrofolate reductase (MTHFR) gene and allergic sensitization in
      Danish adults. OBJECTIVE: We investigated the associations between MTHFR C677T
      and allergy or atopy in a large, population-based birth cohort of children and
      their mothers, the Avon Longitudinal Study of Parents and Children (ALSPAC). We
      also looked for evidence of a pre-natal effect of maternal folate metabolism on
      subsequent atopic disease in the offspring. METHODS: Mothers were recruited in
      pregnancy and the children followed from birth. Atopy in the child was assessed
      at 7-8 years of age by skin prick tests to common allergens. Asthma was defined
      as a physician diagnosis and current symptoms at 71/2 years of age. Asthma and
      allergy status of the mothers were obtained from self-completion questionnaires.
      RESULTS: Data on MTHFR C677T genotype and allergy were available for 5364
      children and on allergy and/or asthma for 7356 mothers. In children, the
      prevalence of atopy was 20.0% and asthma 10.0% whereas in mothers, the prevalence
      of self-reported allergy was 42.7% and asthma 11.5%. Atopy in the child was
      associated with male gender (P<0.001), less tobacco smoke exposure and higher
      maternal education. MTHFR C677T genotype was not associated with social factors
      or dietary folate intake. We found no evidence of associations between the MTHFR
      C677T variant allele and atopy, allergy or asthma in mothers or children. There
      was no evidence to support an effect of maternal MTHFR C677T genotype on atopy in
      the offspring. CONCLUSION: The results of this study do not support the
      hypothesis that impaired folate metabolism is associated with allergy in adults
      or children in this population.

PMID- 18070160
TI  - Seasonal changes in antigen-specific T-helper clone sizes in patients with
      Japanese cedar pollinosis: a 2-year study.
AB  - BACKGROUND: Allergic rhinitis (AR) is a typical type I allergic disease that
      occurs through the induction of allergen-specific effector T cells. Once
      established, new effector T cells derive mostly from memory T cells that are
      capable of surviving for extended periods, although the mechanisms by which these
      memory functions are maintained have not yet been clarified. In particular, the
      exact life-span of memory T cells is still not well understood. OBJECTIVE:
      Pollinosis patients seemed to be suitable subjects to investigate because such
      patients are exposed to antigens strongly for only a limited period once a year.
      We compared the seasonal changes in memory T-helper type 2 (Th2) between
      pollinosis and perennial allergic subjects. METHODS: The clone sizes of the
      Japanese cedar pollen-specific memory Th cells were measured by an ELISPOT assay
      using specific peptides from the patients with cedar pollinosis, and the seasonal
      changes were noted. This study was performed for 2 years. The cedar-specific IgE
      levels in the peripheral blood were also studied. Mite allergy patients were also
      enrolled in the study. RESULTS: The Japanese cedar-specific IL-4-producing Th2
      cells were detected in all patients examined, although the number of cells was
      low. These Th memory cells increased during the pollen season and decreased
      during the off-season. However, more than 60% of the cedar-specific memory Th2
      cells survived up to 8 months after the pollen season. The cedar-specific IgE
      levels exhibited changes similar to the cedar-specific Th cells. On the other
      hand, there was no drifting of Th memory clone size with the mite allergics, and
      the IgE levels also did not change. CONCLUSIONS: While pollen-specific Th cells
      decreased after pollen exposure, their memory functions continued. Memory clone
      size maintenance therefore requires repetitive antigen irritation.

PMID- 18070161
TI  - An immunoglobulin E-reactive chimeric human immunoglobulin G1 anti-idiotype
      inhibits basophil degranulation through cross-linking of FcepsilonRI with
      FcgammaRIIb.
AB  - BACKGROUND: IgE binds to mast cells and basophils via its high-affinity receptor,
      FcepsilonRI, and cross-linking of FcepsilonRI-bound IgE molecules by allergen
      leads to the release of allergic mediators characteristic of type I
      hypersensitivity reactions. Previous work has shown that cross-linking of
      FcepsilonRI with FcgammaRIIb, an ITIM-containing IgG receptor, leads to
      inhibition of basophil triggering. 2G10, a chimeric human IgG1 anti-idiotype, has
      broad reactivity with human IgE and as such has the potential to bind
      simultaneously to FcepsilonRI-bound IgE, via its Fab regions, and the negative
      regulatory receptor, FcgammaRIIb, via its Fc region. OBJECTIVE: To assess the
      ability of human 2G10 to inhibit anti-IgE and allergen-driven basophil
      degranulation through cross-linking of FcepsilonRI-bound IgE with FcgammaRIIb.
      METHODS: 2G10 was assessed for its ability to bind to FcgammaRIIb on transfected
      cells and on purified basophils. In the basophil degranulation assay, basophils
      were purified from peripheral blood of atopic individuals and activated with
      either anti-IgE or the house dust mite allergen Der p 1, in the presence or
      absence of human 2G10. Basophil activation was quantified by analysis of CD63 and
      CD203c expression on the cell surface, and IL-4 expression intracellularly, using
      flow cytometery. RESULTS: Human 2G10 was able to bind to FcgammaRIIb on
      transfected cells and on purified basophils, and induce a dose-dependent
      inhibition of both anti-IgE and Der p 1-driven degranulation of basophils.
      CONCLUSION: The inhibition of basophil degranulation by the human IgG1 anti
      idiotype 2G10 highlights the therapeutic potential of IgE-reactive IgG antibodies
      in restoring basophil integrity through recruitment of the inhibitory receptor
      FcgammaRIIb.

PMID- 18070162
TI  - Animal-derived lipocalin allergens exhibit immunoglobulin E cross-reactivity.
AB  - BACKGROUND: Although knowledge of the IgE cross-reactivity between allergens is
      important for understanding the mechanisms of allergy, the regulation of the
      allergic immune response and the development of efficient modes of allergen
      immunotherapy, the cross-reactivity of animal allergens is poorly known.
      OBJECTIVE: The aim of this study was to characterize IgE cross-reactivities
      between lipocalin proteins, including five animal-derived lipocalin allergens and
      one human endogenous lipocalin, tear lipocalin (TL). METHODS: The recombinant
      proteins were validated by chromatography and mass spectrometry. The IgE-binding
      capacity of the allergens was confirmed by IgE. immunoblotting and IgE immunoblot
      inhibition. IgE ELISA was performed with sera from 42 atopic patients and 21
      control subjects. The IgE cross-reactivities between the lipocalin proteins were
      determined by ELISA inhibition. RESULTS: ELISA inhibition revealed IgE cross
      reactivities between Can f 1 and human TL, between Can f 1 and Can f 2, and
      between Equ c 1 and Mus m 1. Low levels of IgE to human TL were found in the sera
      of seven dog-allergic patients of whom six were IgE-positive for Can f 1.
      CONCLUSION: Several lipocalins exhibited IgE cross-reactivity, probably due to
      the sequential identity of the proteins and also due to similarities in their
      three-dimensional structures. The clinical significance of the findings needs to
      be elucidated. Low-level IgE cross-reactivity can play a role in regulating
      immune response to lipocalin allergens.

PMID- 18070163
TI  - Omalizumab is more effective than suplatast tosilate in the treatment of Japanese
      cedar pollen-induced seasonal allergic rhinitis.
AB  - BACKGROUND: Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is
      a major problem in Japan. Omalizumab, a humanized monoclonal anti-IgE antibody,
      improves symptoms associated with SAR, but a comparative study with an anti
      allergy drug has not yet been conducted. OBJECTIVE: To compare the efficacy and
      safety of omalizumab with suplatast tosilate, a selective T-helper type 2 (Th2)
      cytokine inhibitor, in patients with Japanese cedar pollen-induced SAR. METHODS:
      A randomized, double-blind, double-dummy study was conducted in 308 Japanese
      patients with a history of moderate-to-severe SAR who showed a CAP-RAST value (>
      or =2+) specifically to Japanese cedar pollens. Patients were treated for 12
      weeks with omalizumab plus placebo of suplatast tosilate or suplatast tosilate
      plus placebo of omalizumab. RESULTS: The mean daily nasal symptom medication
      scores (sum of the daily nasal symptom severity score and daily nasal rescue
      medication score) were significantly lower in the omalizumab group than in the
      suplatast tosilate group during three evaluation periods (P<0.001). The
      omalizumab group also had significantly lower mean daily nasal severity scores,
      each of the mean daily nasal and ocular symptom severity scores (sneezing, runny
      nose, stuffy nose, itchy nose, itchy eyes, watery eyes, and red eyes). Omalizumab
      reduced rescue medication requirements, and the proportion of days with any
      rescue medication use in the omalizumab group was significantly lower. Serum-free
      IgE levels markedly decreased in the omalizumab group and it was associated with
      clinical efficacy. The adverse reaction profiles were similar between the two
      groups. The overall incidence of injection site reactions was higher in the
      omalizumab group than in the suplatast tosilate group, but all these events were
      of mild degree. No anti-omalizumab antibodies were detected. CONCLUSION:
      Omalizumab showed significantly greater improvements than suplatast tosilate in
      the treatment of SAR induced by Japanese cedar pollens.

PMID- 18070164
TI  - Oral allergy syndrome and anaphylactic reactions in BALB/c mice caused by soybean
      glycinin and beta-conglycinin.
AB  - BACKGROUND: Soybean protein is used in a number of food products but is also a
      common cause of food allergy. Soybean glycinin and beta-conglycinin represent up
      to one-third of protein in the soybean. Many reports have indicated that glycinin
      and beta-conglycinin have been characterized as major soybean allergens involved
      in food hypersensitivity. OBJECTIVE: To investigate oral allergy syndrome and
      anaphylactic reactions in BALB/c mice caused by soybean glycinin and beta
      conglycinin with an intragastric feeding protocol without using an adjuvant.
      METHODS: BALB/c mice were sensitized by gavages with glycinin and beta
      conglycinin, and allergen-specific IgE and IgG1 responses were studied by a
      passive cutaneous anaphylaxis assay. Serum histamine release and blood pressure
      were measured according to other methods. Epithelium and mast cell dye used the
      method of light microscopy. RESULTS: Sensitization with soybean allergens induced
      high levels of antigen-specific IgE and IgG1 and increased serum histamine in
      BALB/c mice. Percentiles of intact mast cell of small intestine in mice
      sensitized with glycinin and beta-conglyinin significantly decreased for 28 days.
      Degranulation of mast cells and damage of the epithelium in the small intestine
      of mice sensitized with globulins were observed. The level of blood pressure in
      sensitized mice reached a minimum at 3 h. CONCLUSION: Soybean-specific IgE and
      IgG1 antibodies increased, with high levels of histamine release, severe
      degranulation of mast cells and damage of the epithelium of small intestine in
      mice sensitized with glycinin and beta-conglyinin.

PMID- 18070165
TI  - High titre of anti-Ascaris immunoglobulin E associated with bronchial asthma
      symptoms in 5-year-old rural Bangladeshi children.
AB  - BACKGROUND: Increasing interest has arisen whether helminthic infections protect
      against asthma and allergy. The prevalence of wheezing among Bangladeshi children
      is higher in rural areas where helminthic infectious burden is greater, which is
      contrary to the general assumption. OBJECTIVE: We therefore examined the
      association between Ascaris infection, serum level of anti-Ascaris IgE, which
      should be investigated differently from the infection, and wheezing in 5-year-old
      children from rural Bangladesh. METHODS: A total of 219 children who reported
      wheezing during the previous 12 months and 122 randomly selected age-matched
      individuals who had never experienced wheezing were tested for serum levels of
      total and specific Ascaris, Dermatophagoides pteronyssinus, alternaria and
      cockroach IgEs, and for intestinal helminth infection as well. RESULTS: Anti
      Ascaris IgE levels were significantly and independently associated with current
      wheezing during the previous 12 months [odds ratio (OR) per log(e) increment is
      1.31 (95% confidence interval (CI) 1.08-1.60), P=0.007], a history of at least
      four episodes of wheezing [OR per log(e) increment is 1.52 (95% CI 1.18-1.96),
      P=0.001], wheezing with sleep disturbances [OR per log(e) increment is 1.35 (95%
      CI 1.10-1.64), P=0.011] and wheezing with speech disturbances [OR per log(e)
      increment is 1.57 (95% CI 1.19-2.08), P=0.001]. These were adjusted for gender,
      pneumonia history, parental asthma, Trichuris infection, use of dry leaves as
      fuel and other specific IgE levels. The prevalence of Ascaris infection by the
      presence of wheezing was not significantly different (76% vs. 72%, respectively).
      CONCLUSION: We conclude that a high titre of anti-Ascaris IgE is associated with
      an increased risk of asthma symptoms among 5-year-old rural Bangladeshi children
      with a high helminthic infectious load.

PMID- 18070166
TI  - Expansion of circulating Foxp3+)D25bright CD4+ T cells during specific venom
      immunotherapy.
AB  - BACKGROUND: Venom immunotherapy (VIT) induces long-lasting immune tolerance to
      hymenoptera venom antigens, but the underlying mechanisms are not yet clarified.
      Regulatory T cells are thought to play an important role in allergic diseases and
      tolerance induction during specific immunotherapy. AIM: Characterize
      longitudinally the impact of VIT on the pool of circulating regulatory T cells.
      METHODS: Fourteen hymenoptera venom-allergic patients with severe reactions
      (grades III-IV) were studied before, 6 and 12 months after starting ultra-rush
      VIT. Freshly isolated peripheral blood mononuclear cells were surface stained
      with a panel of markers of T cell differentiation and intracellularly for CTLA-4
      and Foxp3 and analysed by flow cytometry. foxp3 mRNA was quantified by real-time
      PCR. VIT responses were assessed by measuring specific IgG4 and IgE levels.
      Eleven individuals with no history of insect venom allergy were studied as
      controls. RESULTS: VIT induces a significant progressive increase in both the
      proportion and the absolute numbers of regulatory T cells defined as CD25bright
      and/or Foxp3+ CD4+ T cells. These changes are not related to alterations in the
      expression of activation markers or imbalances in the naive/memory T cell
      compartments. foxp3 mRNA levels also increased significantly during VIT. Of note,
      the increase in circulating regulatory T cell counts significantly correlates
      with the venom-specific IgG4/IgE ratio shift. CONCLUSION: VIT is associated with
      a progressive expansion of circulating regulatory T cells, supporting a role for
      these cells in tolerance induction.

PMID- 18070167
TI  - Molecular characterization of a human immunoglobulin G4 antibody specific for the
      major birch pollen allergen, Bet v 1.
AB  - BACKGROUND: Allergen-specific IgG4 antibodies induced by specific immunotherapy
      are thought to represent a protective immune response. Objective Our aim was the
      molecular characterization of a human IgG4 antibody (BAB5) specific for the major
      birch pollen allergen Bet v 1 that was derived from an immunotherapy-treated
      patient. METHODS: The cDNA coding for BAB5 was obtained by reverse transcriptase
      PCR from the BAB5-producing cell line, compared with the germ line sequences and
      was expressed as a soluble antibody fragment in Escherichia coli. The epitope
      specificity and cross-reactivity of BAB5 were investigated with recombinant and
      synthetic Bet v 1 fragments and Bet v 1 homologous allergens from pollen. The
      ability of BAB5 to block allergic patients IgE was determined by competition
      experiments and sandwich ELISA. RESULTS: BAB5 is an affinity-matured Bet v 1
      specific IgG4 antibody that reacts exclusively with Bet v 1 but not with Bet v 1
      related allergens. Unlike an earlier-described monoclonal IgG1-blocking antibody,
      BAB1, which had been isolated from the same patient, BAB5 did not block allergic
      patients' IgE reactivity to Bet v 1. CONCLUSION: Our study demonstrates that not
      all allergen-specific IgG antibodies inhibit IgE recognition of allergens and can
      contribute to the success of immunotherapy. The epitope specificity and affinity
      of IgG antibodies but not their isotype are decisive for their protective
      activity.

PMID- 18070168
TI  - Cystic phaeochromocytoma is a distinctive subgroup with special clinical, imaging
      and histological features that might mislead the diagnosis.
AB  - OBJECTIVE: To report and analyse cases of cystic phaeochromocytoma at our
      institution and in previous publications, as adrenal cystic masses are usually
      associated with nonfunctional lesions, but they can be phaeochromocytoma.
      PATIENTS AND METHODS: The prospective adrenalectomy database at our institution
      was reviewed to identify patients with phaeochromocytoma and cystic lesions. The
      clinical, radiological and histological features of cystic phaeochromocytoma were
      evaluated. Other previously published data were identified and compared with the
      present series. RESULTS: In all, there were 107 adrenalectomies at our
      institution from November 2000 to March 2007; 31 of these patients had a
      confirmed diagnosis of phaeochromocytoma and six (19%) were cystic
      phaeochromocytomas. Three of the six cases were asymptomatic and had a negative
      biochemical evaluation (one male and five females, mean tumour size 6.6 cm); the
      imaging diagnosis was mainly based on computed tomography and magnetic resonance
      imaging, and the foremost feature was the enhancement of the tumour rim
      associated with a central cystic mass. Nine other previously published cases were
      reviewed. CONCLUSIONS: From the present large series and previous anecdotally
      reported cases, patients with cystic phaeochromocytomas are more likely to be
      asymptomatic, to complain of chronic abdominal pain, and to have a negative
      biochemical evaluation, which might deter physicians from conducting a full
      evaluation for phaeochromocytoma and mislead the final diagnosis. As such, there
      could be an even higher prevalence of this entity that is yet to be determined.

PMID- 18070169
TI  - Single-institution experience with primary tumours of the male urethra.
AB  - OBJECTIVE: To assess primary tumours of the urethra in males. PATIENTS AND
      METHODS: We retrospectively reviewed our database from 1986 to 2006 for primary
      tumours of the male urethra; nine patients with primary tumours of the urethra
      were analysed and follow-up information was obtained. RESULTS: Three patients had
      tumours of the prostatic urethra, two of which had proliferating focal
      inflammation and one a low-grade, superficial urothelial cancer. All patients
      were treated successfully with transurethral resection. Six patients had
      carcinoma of the bulbar or penile urethra, including two with previous local
      percutaneous radiotherapy for prostate cancer. All had primary surgical excision
      that was adapted to tumour location and extension. One patient had adjuvant
      chemotherapy after surgery. All but one patient remain recurrence-free after a
      median follow-up of 20 months. CONCLUSION: Primary carcinoma of the male urethra
      is a rare entity. Previous radiotherapy might be a predisposing factor. Local
      surgical tumour control is essential for long-term survival, but the extent of
      surgery depends on tumour location and stage. Multimodal therapy might be
      required to obtain an optimum oncological outcome.

PMID- 18070170
TI  - How quality influences the clinical outcome of external beam radiotherapy for
      localized prostate cancer.
AB  - For the delivery of good-quality external beam radiotherapy (EBRT) in localized
      prostate cancer, under-dosage to the peripheral zone (tumour) is one likely cause
      of poor results. The quality is improved by daily verification of the position of
      the prostate, and the use of magnetic resonance imaging (MRI) in delineation.
      Currently these are demands on quality that should be incorporated in each
      radiotherapy department. The use of MRI in staging is also expected to improve
      patient selection for EBRT. Furthermore, an adequate radiation dose should be
      delivered. In this overview we describe what the urologist should expect from
      radiation oncologists to obtain the optimum results for the patients.

PMID- 18070171
TI  - Visualization of the neurovascular bundles and major pelvic ganglion with
      fluorescent tracers after penile injection in the rat.
AB  - OBJECTIVE: To evaluate whether fluorescent tracers can consistently label the
      neurovascular bundles (NVBs) and major pelvic ganglion (MPG) after an
      intracavernosal penile injection, as the reported incidence of erectile
      dysfunction (ED) in men after radical prostatectomy (RP) is 55-65% and thus
      preservation of erectile function, sparing one or both of the NVBs remains one of
      the most vital factors. MATERIALS AND METHODS: Male Sprague-Dawley rats (3 months
      old) received penile injections (20 microL; seven rats/group) of either deionized
      water (DW), Fluoro-Gold (FG), Fast-Blue (FB), Fluoro-Ruby (FR) or green
      fluorescent pseudorabies virus (GF-PRv). The rats were killed at 2, 3 and 14 days
      after injection and the NVBs and MPG were harvested and placed directly under
      fluorescence light. Image analysis was done by computer, coupled to a microscope
      equipped with a digital camera. Each NVB and MPG were analysed for its staining
      pattern and consistency. RESULTS: When compared with the FB, FR and GF-PRv rats,
      the FG-injected rats had better staining of the NVB at 2, 3 and 14 days after
      injection. Under x200, FG highlighted the axons of the cavernous nerve (CN) and
      cell bodies (MPG). This indicates that FG injection into the penis induced the
      strongest CN labelling (positive staining) at 2 and 3 days after injection as
      compared with FB-, FR- and GF-PRv-injected rats. CONCLUSION: FG injection into
      the penis has consistent retrograde staining of the NVBs and MPG after 3 days.
      Therefore, we predict that FG could potentially be used to improve the
      identification of the NVB in other models. However, further studies need to be
      carried out before these tracers can be used in humans.

PMID- 18070172
TI  - Treating asymptomatic patients with hormone-refractory prostate cancer: hormonal
      manipulations for the urologist.

PMID- 18070173
TI  - Inhibitory effects of nicorandil, a K ATP channel opener and a nitric oxide
      donor, on overactive bladder in animal models.
AB  - OBJECTIVES: To investigate the effects of nicorandil, an ATP-sensitive potassium
      (K(ATP)) channel opener with a nitric oxide (NO) donor property, on overactive
      bladder (OAB) in animal models. Nicorandil is currently used clinically to treat
      ischaemic heart disease. MATERIALS AND METHODS: Three animal OAB models were
      used: (i) C-fibre mediated bladder overactivity by infusion of a low
      concentration of acetic acid (AA) into the bladder in female Wistar rats; (ii)
      bladder outlet obstruction (BOO) created by partial urethral obstruction in
      female Wistar rats; and (iii) neuronal NO synthase (nNOS) knockout (KO) mice with
      urinary frequency. The effects of nicorandil and KRN2391, both of which act as
      K(ATP) channel openers and NO donors, on the OAB models were examined. RESULTS:
      Cystometry showed that intravesical instillation of nicorandil and KRN2391
      successfully inhibited OAB induced by intravesical instillation of AA. In the BOO
      model compared with untreated BOO rats, both nicorandil (1 and 3 mg/kg, orally)
      and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency.
      Compared with wild-type mice, nNOS KO mice had urinary frequency with no change
      in the total urine volume. Nicorandil (3 mg/kg, orally) and KRN2391 (1 mg/kg,
      orally) significantly reduced the voiding frequency in nNOS KO mice. CONCLUSIONS:
      Our in vivo results show that nicorandil, a K(ATP) channel opener with a NO donor
      property, can suppress OAB from both neurogenic and myogenic causes. Nicorandil
      appears to be a promising candidate for clinical use in patients with OAB.

PMID- 18070174
TI  - Change in acetylcholine release from rat bladder with partial outlet obstruction.
AB  - OBJECTIVE: To investigate changes in acetylcholine release from the bladder of
      rats with partial bladder outlet obstruction (BOO), as partial BOO leads to
      hypertrophy and an alteration in the contractions of the detrusor smooth muscle,
      and acetylcholine plays an important role in urinary bladder contractions but
      there is little available information on acetylcholine release after BOO.
      MATERIAL AND METHODS: Partial BOO was induced in adult female rats by ligating
      the proximal urethra over a 1 mm angiocatheter; sham-operated rats served as
      controls. The rats were killed 2 weeks, 3 and 6 months after induction of BOO. We
      investigated the contractions induced by carbachol, KCl (80 mm), ATP and
      electrical-field stimulation (EFS, 2.5-40 Hz), and collected the dialysate
      obtained from a microdialysis probe inserted into the muscle strips during EFS,
      and measured the amount of acetylcholine in the dialysate fraction by high
      performance liquid chromatography with electro-chemical detection. S-100
      immunohistochemical staining of the bladder preparations was used for
      histological examination in BOO and control rats. RESULTS: The bladder weight
      gradually increased after BOO. There were no significant changes in KCl-induced
      contractions throughout the experimental period in either group. There were no
      significant changes in carbachol-induced contractions until 3 months after BOO
      but there was a significant reduction at 6 months. ATP-induced contractions were
      significantly increased 2 weeks and 3 months after BOO. EFS-induced contractions
      were gradually reduced after BOO. Acetylcholine release from the bladder strips
      was not significantly different between the groups until 2 weeks after BOO.
      However, acetylcholine release in BOO rats was significantly decreased 3-6 months
      after BOO, being significantly lower than that of the control rats. In the
      histological study, the number of nerve fibres in the BOO rats was significantly
      lower than in the control rats. CONCLUSIONS: We suggest that the prolonged BOO
      caused a decrease in EFS-induced acetylcholine release and the number of nerves
      in the rat urinary bladder, which might contribute to bladder underactivity in
      BOO.

PMID- 18070175
TI  - Transperitoneal left laparoscopic pyeloplasty with transmesocolic access to the
      pelvi-ureteric junction: technique description and results with a minimum follow
      up of 1 year.
AB  - OBJECTIVES: To describe and evaluate the safety and outcome of transperitoneal
      left laparoscopic pyeloplasty (TLLP) with a direct approach to the pelvi-ureteric
      junction (PUJ) through the mesentero-colic space, which avoids mobilization of
      the descending colon. PATIENTS AND METHODS: From March 2005 to June 2006, 18
      consecutive patients underwent TLLP with direct access. For each patient age,
      gender, body mass index (BMI), hospital stay, skin-to-skin operative time, time
      from incision of the posterior peritoneum to dissection of the PUJ, blood loss,
      time to resumption of oral intake and complications were recorded. Statistical
      analysis was used to assess whether the body habitus (BMI <25 kg/m(2) or >25
      kg/m(2)) affected the outcomes. RESULTS: There were no complications during or
      after surgery and no conversions to open surgery were needed. The mean (SD) time
      to resumption of oral intake was 1.36 (0.5) days. The mean hospital stay was 3.3
      (0.67) days and the mean follow-up was 17.4 (4.7) months. There was no
      statistical difference between patients with BMI higher or lower than 25 kg/m(2)
      (P = 0.42). The success rate at 1 year after surgery was 100%. CONCLUSION: TLLP
      with direct access to the PUJ through the mesentero-colic space is a safe and
      effective technique. This approach should be considered for all patients with
      left primary PUJ obstruction who are eligible for a LP and especially for slim
      patients or patients with a large renal pelvis.

PMID- 18070176
TI  - Methylation of the TPEF- and PAX6-promoters is increased in early bladder cancer
      and in normal mucosa adjacent to pTa tumours.
AB  - OBJECTIVE: To evaluate CpG island methylation patterns of cancer-associated genes
      for their applicability as molecular biomarkers for the detection of superficial
      bladder cancer and for the discrimination of invasive from noninvasive tumours.
      PATIENTS AND METHODS: We analysed the methylation status of CpG islands in the
      promoter region of the cancer-associated genes GSTP1, DAPK, MDR1, TPEF, PAX6, and
      TSLC1 in primary papillary bladder cancer specimens from 39 patients (pT1 10,
      pTis one, pTa 20, pT2 five). Tumour-adjacent normal mucosa served as the control.
      The DNAs were bisulphite-treated and submitted to methylation-specific real-time
      polymerase chain reactions. RESULTS: Only TPEF and PAX6 had substantial CpG
      island methylation percentages. The TPEF- and PAX6-promoters also had
      significantly higher methylation rates in tumour tissue compared with the normal
      tumour-adjacent tissue. Interestingly, the methylation rates of the TPEF- and the
      PAX6-promoter were higher in adjacent normal tissues from bladders with pTa then
      in those with pT1 tumours. CONCLUSION: Our results shed a critical light on the
      hypothesis that CpG island hypermethylation of the GSTP1-, DAPK-, MDR1- and TSLC1
      promoter could represent molecular biomarkers for bladder cancer diagnosis and
      detection. However, methylated PAX6- or TPEF-promoters could represent biomarkers
      for this disease. Additional studies are needed to evaluate whether methylation
      rates of these genes in normal bladder tissues are applicable as accessory
      markers for the tumour state or its invasive behaviour.

PMID- 18070177
TI  - Relation of microvessel density with microvascular invasion, metastasis and
      prognosis in renal cell carcinoma.
AB  - OBJECTIVE: To clarify the significance of microvessel density (MVD) in a
      retrospective investigation the relationship between the pattern of MVD
      (reflecting angiogenesis), and tumour stage, grade, size, and occurrence of
      microvessel invasion (MVI), metastasis, and cancer-specific survival (CSS) in
      patients who had surgery for renal cell carcinoma (RCC). PATIENTS AND METHODS:
      Vessels were labelled in sections of formalin-fixed, paraffin-embedded tissues
      from 54 RCCs by CD34 immunohistochemistry. The mean MVD, expressed as the number
      of vessels per 10 high-power fields (HPF, x400) were measured for each case. In
      addition, all pathological slides were reviewed for the presence and absence of
      MVI. The prognostic value of MVD and MVI was then evaluated, and correlated with
      the usual prognostic variables, tumour metastasis and CSS. RESULTS: In a
      univariate analysis of CSS, the MDV tended to be lower as stage increased from
      pT1 to pT3, and as grade increased from G1 to G4, although it was statistically
      significant only for stage (P < 0.001 and 0.050, respectively). The mean MVD was
      higher in 42 nonmetastatic than in 12 metastatic tumours, and in 33 tumours
      associated with MVI than in 21 with no MVI (P < 0.001). The mean MVD was also
      lower and significantly different for 28 large than 26 small tumours (P = 0.005).
      The survival rate of patients with tumours that were small, low-stage, of higher
      MVD, with no MVI and metastasis was significantly higher than that of patients
      with large, high-stage, low MVD, with MVI and metastatic tumours (all P < 0.001).
      MVI was significantly more common with a decreasing trend in MVD and the presence
      of metastasis (Spearman rank correlation r(s) = -0.68, P = 0.01, and r(s) = 0.39,
      P = 0.01, respectively). Independent prognostic factors in a multivariate
      analysis were: in all patients with RCC, tumour stage (P = 0.013) and metastasis
      (P = 0.028); in those with low MVD, MVI (P = 0.004) and metastases (P = 0.016);
      in those with no MVI, stage (P = 0.020); in those with MVI, MVD (P = 0.001); in
      those with no metastases, stage (P = 0.045); and in those with metastases, MVD (P
      < 0.001). No independent predictor was identified in patients with high MVD. In
      patients with no metastases there was a significantly shorter median CSS time in
      RCCs with low MVD and with MVI (P = 0.004 for both). Similarly, patients who had
      grade 3-4 tumours, vs those with lower MVD and with MVI, had a significantly
      shorter median CSS (P = 0.020 for MVD, and 0.01 for MVI). CONCLUSIONS: This study
      suggested that MVD in RCC was inversely associated with MVI, tumour metastasis,
      patient survival and tumour diameter and stage, from the usual prognostic
      variables, but MVD was not an independent prognostic factor in multivariate
      analysis for all patients with RCC. Low MVD and the presence of MVI appears to be
      a marker for identifying patients with an adverse prognosis.

PMID- 18070178
TI  - The effects of a type 4 phosphodiesterase inhibitor and the muscarinic
      cholinergic antagonist tolterodine tartrate on detrusor overactivity in female
      rats with bladder outlet obstruction.
AB  - OBJECTIVE: To investigate the effects of the selective phosphodiesterase (PDE)
      type 4 inhibitor IC485 and the widely used antimuscarinic drug tolterodine
      tartrate on bladder activity in rats with bladder outlet obstruction (BOO), as
      inhibition of PDE4 leads to elevation of intracellular cAMP levels and relaxation
      of smooth muscle. MATERIALS AND METHODS: BOO was induced in female Sprague-Dawley
      rats by tying a silk ligature around the urethra. Six weeks after inducing BOO,
      conscious rats were assessed by cystometry with the urethral ligature intact. The
      effects of IC485 (5, 10 and 50 mg/kg intravenous, i.v.) were examined and
      compared with those of tolterodine (0.01, 0.1 and 1 mg/kg i.v.). RESULTS: IC485
      (5-50 mg/kg i.v.) decreased the number and amplitude of non-voiding contractions
      during the storage phase by 63-88% and 49-83%, respectively; IC485 also increased
      bladder capacity by 28-37%. There was no change in blood pressure after applying
      IC485. Tolterodine tartrate (0.1 and 1.0 mg/kg) significantly decreased the
      number and amplitude of non-voiding contractions by 38-74% and 29-44%,
      respectively, and increased bladder capacity by 19-51%. Whereas voiding
      efficiency and maximum voiding pressure were not altered by IC485 at any dose,
      tolterodine significantly reduced both, by 35-67% and 19-34%, respectively.
      CONCLUSION: Both IC485 and tolterodine tartrate reduced detrusor overactivity in
      rats with BOO. In addition, doses of IC485 that suppressed non-voiding
      contractions had no effect on voiding function. Therefore, selective PDE4
      inhibitors deserve further study as potential agents for treating detrusor
      overactivity in patients with BOO.

PMID- 18070179
TI  - Paraneoplastic Cushing's syndrome in prostate cancer: a difficult management
      problem.
AB  - Cushing's syndrome associated with small-cell de-differentiation of prostate
      cancer is rare, but well described. The detection of Cushing's syndrome in a
      patient with prostate cancer can be problematical, and when occurring in prostate
      cancer nearly always implies the development of small-cell transformation.
      Testosterone levels in these patients are likely to be in the normal range,
      despite previous castration. The features of Cushing's syndrome contribute
      considerably to patients' morbidity and probably to their mortality. The syndrome
      is unlikely to be controlled with inhibitors of steroid synthesis, and
      chemotherapy is likely to be poorly tolerated, resolving the syndrome in only a
      few patients. We suggest that bilateral adrenalectomy at an early stage should be
      considered, possibly as a preliminary to anticancer treatments.

PMID- 18070180
TI  - Serendipity in urology.

PMID- 18070181
TI  - Sacral neuromodulation for treating the symptoms of overactive bladder syndrome
      and non-obstructive urinary retention: >10 years of clinical experience.

PMID- 18070182
TI  - Endometriosis of the vermiform appendix as an exceptional cause of acute
      perforated appendicitis during pregnancy.
AB  - The incidence of appendicitis presenting during pregnancy is less than 1 in 1500.
      Most cases of endometriosis of the appendix are discovered as a result of
      incidental appendectomy. True perforated appendicitis in an endometriotic area
      has not been reported before. The authors report the case of a 28-year-old woman
      in her 27th week of pregnancy who underwent an appendicectomy for inflamed,
      perforated appendix with transmural endometriosis and accompanying decidual
      reaction.

PMID- 18070183
TI  - Multivisceral resections for locally advanced rectal cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of en bloc
      multivisceral resection of organs involved by locally advanced rectal carcinoma.
      METHOD: A total of 312 patients with primary rectal cancer underwent surgery
      between January 1994 and April 2005. Of these, 57 patients (18.3%) had
      macroscopically direct invasion of an adjacent organ or structure, and underwent
      multivisceral resection with curative intent. Survival analyses were made by the
      Kaplan-Meier and the Cox proportional hazards regression model. RESULTS: The
      postoperative mortality was 3.5%. The overall survival rate at 1, 3 and 5 years
      was 96.4%, 81.6% and 49.0%. Age (> or = 65 years), depth of tumour invasion (pT3
      stage), lymph node status (pN0), tumour stage (III A-B), grading (G1), vascular
      and neural invasion (not extensive), type of adhesion (inflammatory) and type of
      resection (R0) were significant factors favouring survival in the univariate
      analysis. Only two factors, lymph node status pN0 (P = 0.007) and R0 resection (P
      = 0.005) were independently significant factors in the multivariate analysis.
      CONCLUSION: R0 resection and pN0 status influence overall survival for locally
      advanced rectal carcinoma.

PMID- 18070184
TI  - Pathologic response assessed by Mandard grade is a better prognostic factor than
      down staging for disease-free survival after preoperative radiochemotherapy for
      advanced rectal cancer.
AB  - OBJECTIVE: The reduction in tumour stage induced by full course radiotherapy plus
      chemotherapy is apparent from histological changes. The purpose of this study was
      to determine the rate of complete pathological response and to evaluate the
      prognostic value for disease free survival (DFS) and disease specific survival
      (DSS) of the response. The relation between pretreatment variables (age, gender,
      stage, tumour height and [carcinoembryogenic antigen (CEA)] and postsurgical
      variables was compared to the pathological response. METHOD: A total of 119
      patients with stage II or III rectal cancer underwent surgery 6 weeks after
      neoadjuvant treatment. Group A included patients with a complete or good
      pathological response (Mandard grade I-II) and group B patients with a poor
      response (Mandard grade III-IV-V). The pretreatment endo-rectal ultrasound scan
      stage was compared with histopathology stage of the resected specimen. DFS and
      DSS were compared using the log-rank test. RESULTS: All 119 patients (mean age
      67.9 years, 83 males) underwent resection. The tumour was located in the upper,
      middle and lower third of the rectum in 11, 51 and 57 patients. 88 patients had a
      low anterior resection, 28 patients abdomino-perineal resection and three a
      Hartmann's operation. There was no postoperative death. The circumferential
      margin (CM) was involved in 10%. A complete pathological response was observed in
      17 (14.2%) patients. Thirty-six (30.2%) patients had a group A and 83 a group B
      response. Group A showed DFS to be significantly higher than group B (log rank: P
      = 0.007). The DSS rate was not significantly different between the two groups
      (log rank P = 0.113). Down-staging was not related with DFS. No relation was
      found between pretreatment variables and response. A good pathological response
      was related to a lower rate of permanent colostomy but not with CM involvement or
      the number of lymph nodes. CONCLUSION: Tumour regression of grades I or II was a
      good indicator of DFS in locally advanced rectal cancer, treated by neoadjuvant
      chemotherapy and radiotherapy. Patients with a high regression grade were
      associated with a lower incidence of definitive stoma formation. The regression
      grade was shown to be a better prognostic factor than down-staging.

PMID- 18070185
TI  - The management and outcome of anastomotic leaks in colorectal surgery.
AB  - PURPOSE: Anastomotic leaks in colorectal surgery are associated with significant
      morbidity and mortality and may result in poor functional and oncological
      outcomes. Diagnostic difficulties may delay identification and appropriate
      management of leaks. The aim of this study was to look at the diagnosis, clinical
      management and outcomes of anastamotic leaks in our department. METHOD: A
      retrospective audit and case note review of all patients who underwent the
      formation of a colorectal anastomosis between January 1996 and December 2002 (n =
      1421) was performed. An anastomotic leak was defined as sepsis identified to have
      arisen from an anastomosis that subsequently required surgery, radiological
      drainage or intravenous antibiotics. Forty-one patients (25 male, 16 female) with
      a median age of 60 years (range 7-89 years) were identified as having suffered an
      anastomotic leak. RESULTS: The median time to diagnosis of an anastomotic leak
      following surgery was 7 days (range 3-29). At re-operation, 21 patients (51%)
      underwent formation of a stoma, and any who required the anastomosis to be
      formally taken down have been left with a 'permanent' stoma. Currently only four
      of 12 patients (33%) who required a stoma for an anastomotic leak following
      anterior resection have undergone stoma reversal. Eleven of 16 patients (69%) who
      had received a stoma following another colorectal procedure had undergone stoma
      reversal. The mortality associated with an anastamotic leak in this series was 5%
      (n = 2). CONCLUSION: Although anastomotic leaks following colorectal surgery are
      associated with significant morbidity and stoma formation, early and aggressive
      management should result in a low overall mortality. If an anastomosis is taken
      down following an anastomotic leak after anterior resection, this will usually
      result in a 'permanent' stoma.

PMID- 18070186
TI  - A high pretreatment plasma oestradiol level is associated with a low risk of
      acute myocardial infarction in parenteral oestrogen therapy for locally advanced
      prostate cancer.
AB  - OBJECTIVE: To evaluate the relationship of pretreatment plasma oestradiol (ppE2)
      and testosterone (ppT) level to acute myocardial infarction (AMI) in patients
      with locally advanced prostate cancer primarily treated with parenteral
      polyoestradiol phosphate (PEP) or orchidectomy, considering the effect of age,
      performance status, pretreatment diseases and medication, and tumour stage and
      grade. PATIENTS AND METHODS: The present Finnprostate 6 study comprised 234
      patients randomized to oestradiol or intramuscularly administered PEP (240
      mg/month) therapy. Each patient was followed until the end of the primary therapy
      (up to 10 years) or until the first AMI (lethal or not). RESULTS: The risk of
      AMI, when the PEP and orchidectomy groups were analysed together, was lower in
      patients with a high ppE2 level, and this risk was independent of the ppT level,
      pretreatment diseases, medication, age, performance status, disease stage or
      grade. In the PEP therapy group the risk of AMI was statistically significantly
      lower in patients with a high ppE2 level (>or=93 pmol/L) than in those with a low
      ppE2 level (<93 pmol/L; risk ratio 0.28, 95% confidence interval 0.10-0.84, P =
      0.022). There was no such difference in the orchidectomy group. The ppT level had
      no association with the risk of AMI. CONCLUSIONS: A high ppE2 level is associated
      with a low risk of AMI in patients with locally advanced prostate cancer treated
      with PEP; there was no such association for ppT level. In the orchidectomy group
      the ppE2 or ppT level was not statistically significantly associated with the
      risk of AMI.

PMID- 18070187
TI  - Comparison of cancers detected at only a sextant or alternative location.
AB  - OBJECTIVES: To evaluate the effect of the tumour-positive biopsy site at extended
      biopsy on tumour volume and potential biological significance of prostate cancer.
      PATIENTS AND METHODS: We retrospectively evaluated radical prostatectomy
      specimens from 247 consecutive men diagnosed with prostate cancer by extended
      biopsy. Men who had both a positive sextant and alternative site were excluded,
      resulting in 132 evaluable men. We assessed age, pretreatment prostate-specific
      antigen (PSA) level, prostate volume, pathological stage, Gleason score, total
      tumour volume, and location (sextant or alternative site) of the positive biopsy.
      Patients were grouped by location of the positive biopsy, i.e. sextant site only
      or alternative site only, including anterior horn, midline region and transition
      zone. RESULTS: A biopsy from a sextant-only or an alternative site only was
      positive in 42% (56/132) and 58% (76/132) of men, respectively. There was no
      significant difference in PSA level, number of positive cores, pathological
      stage, Gleason score, total tumour volume or the incidence of low-volume/low
      grade cancer (volume <0.5 mL and a Gleason score of </=6) between the groups. In
      men with one positive core, there was no significant difference in total tumour
      volume (median 0.20 vs 0.36 mL, respectively) or in the incidence of low
      volume/low-grade cancer (42% vs 40%, respectively) between the groups.
      CONCLUSIONS: Total tumour volume and the incidence of low-volume/low-grade cancer
      detected at an alternative site only were comparable to those of cancers detected
      at a sextant site only. Alternative site biopsy did not increase the incidence of
      low-volume/low-grade cancers detected.

PMID- 18070188
TI  - Dietary patterns and surgically treated benign prostatic hyperplasia: a case
      control study in Western Australia.
AB  - OBJECTIVES: To investigate dietary patterns and food intake as risk factors for
      surgically treated benign prostatic hyperplasia (BPH), as few risk factors have
      been established for BPH and recently there has been some interest in a role for
      diet in the development of BPH. PATIENTS, SUBJECTS AND METHODS: A case-control
      study was conducted in Western Australia (WA) during 2001 and 2002. BPH cases
      were men with a diagnosis of BPH hospitalized for their first prostatectomy.
      Controls were frequency matched for age and sex from the WA electoral roll. A
      previously evaluated food-frequency questionnaire (FFQ) collected information on
      usual dietary intake 10 years earlier. Factor analysis identified dietary
      patterns in the FFQ data. Effects of dietary patterns and food intakes on the
      risk of BPH were examined using unconditional logistic regression, adjusting for
      various confounders. RESULTS: In all, 406 cases and 462 controls (aged 40-75
      years) provided data. Three dietary patterns were identified, i.e. 'Vegetable',
      'Western' and 'Health Conscious'. BPH risk was not associated with the 'Health
      Conscious' or 'Western' patterns, but there was a lower risk with an increasing
      score for the 'Vegetable' pattern (odds ratio 0.78, 95% confidence interval 0.63
      0.98). BPH risk was significantly and inversely related to the intake of total
      vegetables, dark yellow vegetables, other vegetables, tofu and red meat. There
      was a higher risk of BPH with increasing intake of high-fat dairy products.
      CONCLUSIONS: These results indicate that vegetables, soy products, red meat and
      high-fat dairy foods might be important in the development of BPH.

PMID- 18070189
TI  - En bloc stapler ligation of the renal vascular pedicle during laparoscopic
      nephrectomy.
AB  - OBJECTIVES: To evaluate, in a prospective series of laparoscopic nephrectomies
      (LNs), the safety and feasibility of en bloc stapling for resection and occlusion
      of the vascular renal pedicle. PATIENTS AND METHODS: Between October 2003 and
      March 2006, we investigated the intra- and postoperative outcomes in patients
      undergoing planned en bloc stapling of the renal vein and artery during LN. We
      also assessed complications at 6 and 12 months. RESULTS: In all, 57 patients,
      with a mean (range) age of 59.8 (10-83) years, were enrolled. The indications for
      LN were: renal cell carcinoma (RCC) in different stages in 66.7%, transitional
      cell carcinoma in 3.5% and oncocytoma in 5.2%. In a further 19.2% the patients
      presented with nontumoral lesions and the remaining 5.4% consisted of several
      rarer entities. The mean (sd) tumour size was 4.7 (1.75) cm. In one case (1.8%) a
      conversion to open nephrectomy was necessary because of a stapling device
      failure. Three patients (5.4%) underwent revision for bleeding. The median
      (range) blood loss was 100 (50-1000) mL. The median operating duration was 145
      (95-410) min; in 19.3% this included additional surgical or diagnostic
      procedures. At 6 and 12 months after LN, there were no complications related to
      the surgical technique, in particular there was no arterio-venous fistula.
      CONCLUSIONS: We conclude that in our prospective series, en bloc stapling of the
      renal vascular pedicle during LN was a safe technique and that it was feasible in
      a time at the lower limit of the range of reported durations for similar
      procedures.

PMID- 18070190
TI  - Bacteriuria in patients with an orthotopic ileal neobladder: urinary tract
      infection or asymptomatic bacteriuria?
AB  - OBJECTIVE: To investigate the prevalence of asymptomatic bacteriuria (ABU) and
      urinary tract infection (UTI), and the local and systemic inflammatory response,
      in patients with ileal neobladder. PATIENTS AND METHODS: The study included 40
      patients who had a radical cystectomy and ileal neobladder. Two urine samples,
      one for chemical and physical analysis, and cytofluorimetry, and one for urine
      culture, were collected every 3 months for 9 months after surgery. RESULTS: Of
      119 urine cultures, 69 (57%) were positive for bacteria. Only nine of the 40
      patients had no bacteriuria on urine culture. Escherichia coli strains were
      cultured from eight of 10 patients with persistently positive urine. The
      incidence of bacteriuria was different according to gender. There was a high
      concentration of leukocytes (0-6 microL) in 118 of 119 samples. The mean
      concentration of leukocytes in sterile urine culture was 1181/microL, while in
      patients with ABU the mean was 491 (P < 0.05). CONCLUSION: A positive urine
      culture is a very common finding in patients with an orthotopic bladder. The most
      interesting results was the absence of elevated inflammatory indices and/or
      symptoms, even in those patients with high levels of bacteriuria. Probably this
      is due to the completely different inflammatory response of ileal mucosa against
      bacteria than has bladder mucosa. Indeed, the leukocyte concentration detected in
      urinary sediment was inversely association with bacterial growth in urine
      cultures. These findings suggest a redefinition of ABU and UTI in patients with
      an orthotopic neobladder.

PMID- 18070191
TI  - Targeting the receptor activator of nuclear factor-kappaB (RANK) ligand in
      prostate cancer bone metastases.
AB  - Newly formed bone in the typically osteoblastic bone metastases from prostate
      cancer shows characteristics of woven bone, e.g. marked defects in mineralization
      and microstructure. Adding to the reduced mechanical strength of prostate cancer
      bone metastasis is an increasingly recognized osteolytic component. The existence
      of osteoclasts in osteoblastic bone metastases and concomitant increases in urine
      or serum markers for bone resorption are reported in affected patients.
      Pathologically increased osteoclastic bone resorption is a key mediator of the
      clinical complications from bone metastases, among them fractures, spinal cord
      compression and bone pain. The receptor activator of nuclear factor (NF)-kappaB
      ligand (RANKL) pathway has been identified as the main driving force for
      osteoclastogenesis and resulting bone resorption. Emerging data indicate that
      bone marrow-derived RANKL might also constitute a chemoattractant factor for RANK
      expressing tumour cells that is likely to contribute to the pathogenesis of bone
      metastases, including those arising from prostate cancer. Cumulative evidence
      supports RANKL inhibition as a therapeutic goal for the treatment and prevention
      of bone metastases from prostate cancer.

PMID- 18070192
TI  - Evaluation of a synchronous twin-pulse technique for shock wave lithotripsy: a
      prospective randomized study of effectiveness and safety in comparison to
      standard single-pulse technique.
AB  - OBJECTIVE: To asses the efficacy and safety of bidirectional synchronous twin
      pulse extracorporeal shock wave lithotripsy (ESWL) compared with standard ESWL.
      PATIENTS AND METHODS: Between March 2003 and December 2006, 240 patients with a
      radio-opaque single renal stone of <or=25 mm were randomized to treatment either
      by the Twinheads (TH) lithotripter (FMD, Lorton, Virginia, USA) or the Dornier
      Lithotripter S (DLS, Dornier MedTech Europe GmbH, Germering, Germany). Before and
      after ESWL, urinary N-acetyl-B-glucosaminidase (NAG) levels were assessed and
      patients were evaluated with dynamic MRI. The efficacy and complications were
      compared, with success defined as no residual fragments. RESULTS: For stones of
      >10 mm the rate for the failure of disintegration was 13.3% for the DLS vs 1.4%
      for the TH (P = 0.009). For stones of <or=10 mm the stone-free rate was 74.4% for
      the TH vs 67.7% for the DLS (P = 0.6), while for stones of >10 mm it was 78.1%
      and 66.7%, respectively (P = 0.14). The median (range) number of sessions in both
      groups was 2 (1-5). After ESWL urinary NAG levels were increased significantly in
      both groups; in the TH group it declined below the level before ESWL after 2
      days, while in the DLS group it remained high after 7 days. In the DLS group four
      patients developed subcapsular or parenchymal haematoma after ESWL, vs none in
      the TH group. There was loss of corticomedullary differentiation after ESWL in
      three patients in the DLS group and only one in the TH group. In the DLS group
      there was a statistically significantly decrease in bilateral renal perfusion
      after ESWL, but no changes in the TH group. CONCLUSIONS: Synchronous twin-pulse
      ESWL has clinical advantages over standard ESWL in terms of safety and efficacy.

PMID- 18070193
TI  - Systemic therapy for metastatic urothelial carcinoma.

PMID- 18070194
TI  - Analysis of single items on the Self-Esteem and Relationship questionnaire in men
      treated with sildenafil citrate for erectile dysfunction: results of two double
      blind, placebo-controlled trials.
AB  - OBJECTIVE: To evaluate the effect of sildenafil citrate on each item of the 14
      item Self-Esteem And Relationship (SEAR) questionnaire, which is used to measure
      self-esteem, confidence, satisfaction with sexual relationship, and overall
      relationship satisfaction in men with erectile dysfunction (ED). PATIENTS AND
      METHODS: Data were combined from two 12-week, double-blind, placebo-controlled,
      flexible-dose sildenafil trials having identical protocols, one conducted in the
      USA and the other in Mexico, Brazil, Australia and Japan. All men had ED and were
      aged >or=18 years. Response categories of each SEAR item used a 4-week reference
      period and were based on a five-point scale (1, almost never/never; 2, a few
      times; 3, sometimes; 4, most times; 5, almost always/always). The difference
      (sildenafil vs placebo) in the change from baseline to week 12 was evaluated with
      a Wilcoxon rank sum test using ridit analysis, and an analysis of covariance
      model that included treatment group, centre, study and baseline item score.
      RESULTS: Compared with the 274 patients receiving placebo, the 279 receiving
      sildenafil reported significantly greater mean and median improvements (P <
      0.001) in each of the 14 SEAR items. The probability of increased psychosocial
      benefit from baseline to week 12 was higher with sildenafil for each SEAR item,
      and ranged from 0.60 ('My partner was unhappy with the quality of our sexual
      relations'[item reverse-scored]) to 0.72 ('I was satisfied with my sexual
      performance'). Across all items, the mean (sd) probability was 0.67 (0.04) that a
      randomly selected patient in the sildenafil group would have a more favourable
      change relative to a randomly selected patient in the placebo group. CONCLUSIONS:
      Sildenafil produced substantial and meaningful improvements at the item-specific
      level. This analysis complements previously published work on self-esteem,
      confidence and relationship satisfaction.

PMID- 18070195
TI  - Synergistic effects in neuromuscular activation and calcium-sensitization in the
      bladder trigone.
AB  - OBJECTIVE: To elucidate possible synergistic effects between adrenergic,
      muscarinic, and purinergic neuromuscular activation in the bladder trigone, and
      to examine the relevance of the Rho-kinase (ROCK)/protein kinase C (PKC) pathway
      as a possible underlying mechanism. MATERIALS AND METHODS: Muscle strips were
      dissected from the superficial trigone of male guinea-pigs. Contractions were
      elicited by electrical-field stimulation (EFS: 0.1 ms pulses, 1-64 Hz for 3 s) or
      exposure to exogenous agonists. RESULTS: There was evidence for functional
      adrenergic, purinergic, and muscarinic neurotransmission. Selective inhibition of
      individual components suggested synergistic interactions. The mean (sd) EFS
      contractions were enhanced by carbachol (0.3 microm) and phenylephrine (10
      microm) to 2.4 (0.4) and 6.4 (1.5)-fold of control (32 Hz), respectively.
      Phenylephrine (10 microm) also augmented contractions induced by carbachol (1
      microm) to 3.9 (1.2)-fold of control, alpha,beta-methylene ATP (1 microm) to 4.3
      (0.4) and 20 mm superfusate K(+) to 5.0 (2.0). The PKC inhibitors GF 109203X (5
      microm) and H-7 (100 microm), as well as the ROCK inhibitor Y-27632 (5 microm)
      reduced the phenylephrine contracture to 37.3 (7.4), 38.5 (11.2) and 54.9 (7.8)%
      of control, respectively. With the exception of H-7 they had no significant
      effect on the carbachol response. CONCLUSION: This study shows a synergistic
      effect between adrenergic, muscarinic, and purinergic receptor activation on the
      muscle of the superficial trigone. The study suggests that Ca(2+)-sensitization
      of contractile proteins plays a key role in this synergism, particularly for
      adrenergic activation.

PMID- 18070196
TI  - Initial clinical experience with real-time transrectal ultrasonography-magnetic
      resonance imaging fusion-guided prostate biopsy.
AB  - OBJECTIVE: To evaluate the feasibility and utility of registration and fusion of
      real-time transrectal ultrasonography (TRUS) and previously acquired magnetic
      resonance imaging (MRI) to guide prostate biopsies. PATIENTS AND METHODS: Two
      National Cancer Institute trials allowed MRI-guided (with or with no US fusion)
      prostate biopsies during placement of fiducial markers. Fiducial markers were
      used to guide patient set-up for daily external beam radiation therapy. The
      eligible patients had biopsy-confirmed prostate cancer that was visible on MRI. A
      high-field (3T) MRI was performed with an endorectal coil in place. After moving
      to an US suite, the patient then underwent TRUS to visualize the prostate. The US
      transducer was equipped with a commercial needle guide and custom modified with
      two embedded miniature orthogonal five-degrees of freedom sensors to enable
      spatial tracking and registration with MR images in six degrees of freedom. The
      MRI sequence of choice was registered manually to the US using custom software
      for real-time navigation and feedback. The interface displayed the actual and
      projected needle pathways superimposed upon the real-time US blended with the
      prior MR images, with position data updating in real time at 10 frames per
      second. The registered MRI information blended to the real-time US was available
      to the physician who performed targeted biopsies of highly suspicious areas.
      RESULTS: Five patients underwent limited focal biopsy and fiducial marker
      placement with real-time TRUS-MRI fusion. The Gleason scores at the time of
      enrollment on study were 8, 7, 9, 9, and 6. Of the 11 targeted biopsies, eight
      showed prostate cancer. Positive biopsies were found in all patients. The entire
      TRUS procedure, with fusion, took approximately 10 min. CONCLUSION: The fusion of
      real-time TRUS and prior MR images of the prostate is feasible and enables MRI
      guided interventions (like prostate biopsy) outside of the MRI suite. The
      technique allows for navigation within dynamic contrast-enhanced maps, or T2
      weighted or MR spectroscopy images. This technique is a rapid way to facilitate
      MRI-guided prostate therapies such as external beam radiation therapy,
      brachytherapy, cryoablation, high-intensity focused ultrasound ablation, or
      direct injection of agents, without the cost, throughput, or equipment
      compatibility issues that might arise with MRI-guided interventions inside the
      MRI suite.

PMID- 18070197
TI  - Circulating endothelial cells as a therapeutic marker for thalidomide in combined
      therapy with chemotherapy drugs in a human prostate cancer model.
AB  - OBJECTIVE: To investigate how thalidomide confers its survival benefit in
      prostate cancer, by assessing its effect on circulating endothelial cells (CECs)
      and progenitors (CEPs) in a combined therapy of thalidomide and chemotherapy
      drugs in a human prostate cancer xenograft model, as in clinical trials patients
      treated with both thalidomide and docetaxel had a >50% decrease in prostate
      specific antigen (PSA) levels and longer median overall survival than those
      treated with docetaxel monotherapy. MATERIALS AND METHODS: A human prostate
      cancer xenograft model was used to evaluate the effect of either thalidomide,
      docetaxel or a combination of the two drugs on circulating ECs. Drug treatment
      was continued for 17 days, and tumours were measured two or three times a week.
      Blood samples were taken at three different time points: before the treatments, 4
      days and 17 days into the treatments, and CECs and CEPs were measured by flow
      cytometry analysis. RESULTS: There was an increased level of apoptotic/dead CECs
      shortly after the intravenous injection of docetaxel, and the addition of
      thalidomide further increased the apoptotic/dead CEC level, showing that
      thalidomide enhances the cytotoxicity of docetaxel against tumour vascular ECs.
      CONCLUSION: Thalidomide increased the apoptotic/dead CEC level and enhanced the
      cytotoxicity of docetaxel against tumour vascular ECs, confirming its
      antiangiogenic property in vivo in combined anticancer treatments. In addition,
      there was a correlation between the increased apoptotic/dead CEC levels early in
      the treatment and antitumour efficacy later, suggesting that the apoptotic/dead
      CEC level could be used as a marker, at an early stage, to predict tumour
      response to antiangiogenic therapies.

PMID- 18070198
TI  - Activity of different phospholipids in attenuating hyperactivity in bladder
      irritation.
AB  - OBJECTIVE: To evaluate the effect of liposomes prepared from various natural and
      synthetic lipids in a rat bladder injury model in the absence or the presence of
      cholesterol and to elucidate the key structural elements necessary for the
      efficacy of liposomes required for alleviating bladder hyperactivity. MATERIALS
      AND METHODS: The intravesical pressure was recorded using a transurethral
      catheter in adult female Sprague-Dawley rats anaesthetized with urethane (1.0
      g/kg subcutaneously). Continuous cystometrograms (CMGs) were obtained by slowly
      filling the bladder with solutions of varying compositions after obtaining a
      baseline CMG with saline. Rat urothelium was injured with protamine sulphate (PS)
      and irritated by subsequent infusion of KCl (500 mm) for 1 h. Thereafter,
      liposomes prepared in KCl using several natural and synthetic phospholipids were
      infused for 2 h. The percentage reduction in bladder contraction frequency (BCF)
      was used as a comparative variable for judging the activity of different
      phospholipids. RESULTS: Exposure of rat bladder to sequential infusion of PS and
      KCl increased its BCF and empty liposomes of uncharged zwitterionic phospholipids
      markedly attenuated the PS-induced irritation and decreased the raised BCF. But
      empty liposomes prepared with either cationic or anionic charged lipids were not
      able to achieve the same effect. Addition of cholesterol did not significantly
      increase their efficacy. Optimal efficacy of liposomes was achieved with
      phosphatidylcholines with longer acyl chains and saturation in only one of the
      two acyl chains. CONCLUSIONS: These in vivo studies show that phospholipids
      attenuate the bladder irritation from KCl after PS-induced bladder injury.

PMID- 18070199
TI  - Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence.
AB  - OBJECTIVE: To evaluate the urodynamic data before and 6 months after implantation
      of sacral neuromodulation (SNM, an established treatment for voiding dysfunction,
      including refractory urge urinary incontinence, UI) and to assess the correlation
      between the urodynamic data and clinical efficacy in patients with UI. PATIENTS
      AND METHODS: In all, 111 patients with a >50% reduction in UI symptoms during a
      percutaneous nerve evaluation test qualified for surgical implantation of SNM.
      Patients were categorized in two subgroups, i.e. those with UI with or without
      confirmed detrusor overactivity (DO) at baseline. At the 6-month follow-up all
      patients had a second urodynamic investigation, with the stimulator switched on.
      RESULTS: At baseline, there was urodynamically confirmed DO in 67 patients, while
      44 showed no DO. A review of filling cystometry variables showed a statistically
      significant improvement in bladder volumes at first sensation of filling (FSF)
      and at maximum fill volume (MFV) before voiding for both UI subgroups, compared
      with baseline. In 51% of the patients with UI and DO at baseline, the DO resolved
      during the follow-up. However, those patients were no more clinically successful
      than those who still had DO (P = 0.73). At the 6-month follow-up, 55 of 84
      implanted patients showed clinical benefit, having a >or=50% improvement in
      primary voiding diary variables. Patients with UI but no DO had a higher rate of
      clinical success (73%) than patients with UI and DO (61%), but the difference was
      not statistically significant. CONCLUSION: These urodynamic results show a
      statistically significant improvement in FSF and MFV in patients with UI with or
      with no DO after SNM. Although there was a urodynamic and clinical improvement in
      both groups, patients with UI but no DO are at least as successful as patients
      with UI and DO. Therefore in patients with UI, DO should not be a prerequisite
      selection criterion for using SNM.

PMID- 18070200
TI  - Increase in nuclear translocation of nuclear transcription factor-kappaB
      following infection of a human Schwann cell line with Leishmania amazonensis.

PMID- 18070201
TI  - Anastrozole-induced subacute cutaneous lupus erythematosus.

PMID- 18070202
TI  - Adrenergic urticaria in a patient with cholinergic urticaria.

PMID- 18070203
TI  - A novel missense mutation in RSPO4 gene underlies autosomal recessive congenital
      anonychia in a consanguineous Pakistani family.

PMID- 18070204
TI  - Repair of photoaged dermal matrix by topical application of a cosmetic
      'antiageing' product.
AB  - BACKGROUND: Photoaged skin is characterized by coarse and fine wrinkles. The
      mechanism of wrinkle formation appears to involve changes to components of the
      dermal extracellular matrix. Topical treatment with all-trans retinoic acid (RA)
      can repair photoaged dermal matrix; this is regarded as the 'gold standard'
      against which repair agents are judged. To date, little is known regarding the
      ability of over-the-counter 'antiageing' products to repair photoaged skin.
      OBJECTIVES: We used a modified occluded patch test to ascertain whether topical
      applications of cosmetic 'antiageing' products are able to repair photoaged human
      skin. METHODS: Commercially available test products [basic moisturizer,
      'antiageing' cream containing different active complex levels (6% active:
      lipopentapeptide, white lupin peptides, antioxidants, retinyl palmitate; 2%
      active: lipopentapeptide, white lupin peptides, antioxidants)] were applied under
      occlusion for 12 days prior to biopsy and histological assessment in photoaged
      volunteers (n=9). RA was used as a positive control. RESULTS: In agreement with
      previous studies, the patch-test study revealed that RA produced significant
      fibrillin-1 deposition in the papillary dermis (P<0.01) but had little effect on
      procollagen I or matrix metalloproteinase-1 expression. The 6% total active
      complex formulation, however, increased the deposition of fibrillin-1 and
      procollagen I (P<0.01, P<0.05, respectively). CONCLUSIONS: This study indicates
      that in an in vivo 12-day patch test an over-the-counter cosmetic product can
      induce changes in photoaged dermal extracellular matrix, which are indicative of
      repair.

PMID- 18070205
TI  - Update on the pathogenesis of post-transplant skin cancer in renal transplant
      recipients.
AB  - Remarkable advances in the field of transplantation over the last several decades
      have benefited many thousands of patients. Five-year survival ranges from 90% for
      a live donor renal transplant to 85% for a cadaveric renal transplant. However,
      with this success come the complications of chronic immunosuppression. Lifelong
      immunosuppressive treatment for adequate graft function results in reduction of
      immunosurveillance, with increased risk of various cancers leading to substantial
      morbidity and mortality in these patients. This review discusses multifactorial
      intrinsic and extrinsic factors contributing to the pathogenesis of skin cancers
      in renal transplant recipients and reviews potential solutions.

PMID- 18070206
TI  - Development of an enhanced proteomic method to detect prognostic and diagnostic
      markers of healing in chronic wound fluid.
AB  - BACKGROUND: Chronic venous leg ulcers are a significant cause of pain, immobility
      and decreased quality of life for patients with these wounds. In view of this,
      research efforts are focused on multiple factors in the wound environment to
      obtain information regarding the healing of ulcers. OBJECTIVES: Chronic wound
      fluid (CWF), containing a complex mixture of proteins, is an important modulator
      of the wound environment, and therefore we hypothesized that these proteins may
      be indicators of the status of wounds and their potential to heal or otherwise.
      To explore this we developed and validated a proteomic approach to analyse CWF.
      METHODS: In this study, pooled CWF was depleted of high abundant proteins using
      immunoaffinity chromatography. The flow-through and bound fractions were
      collected, concentrated, desalted and analysed using a range of techniques. Each
      fraction was further separated using two-dimensional (2D) gel electrophoresis and
      2D liquid chromatography and analysed using mass spectrometry (MS). RESULTS:
      Western blot analysis against three high abundant proteins confirmed the
      selective removal of these proteins from CWF. Critically, one-dimensional and 2D
      gel electrophoresis indicated that subsequent removal of these proteins enhanced
      the ability to detect proteins in low abundance in CWF. Further, MS demonstrated
      that depletion of these abundant proteins increased the detection of other
      proteins in these samples. CONCLUSIONS: Results obtained indicate that this
      approach significantly improves separation of proteins present in low
      concentrations in CWF. This will facilitate the identification of biomarkers in
      samples collected from patients with ulcers and lead to improved patient
      therapies and wound care approaches.

PMID- 18070207
TI  - Genotyping of HLA-I and HLA-II alleles in Chinese patients with paraneoplastic
      pemphigus.
AB  - BACKGROUND: Class I and class II HLA genes are thought to play a role in the
      immunopathogenesis of bullous dermatoses such as pemphigus vulgaris and pemphigus
      foliaceus, but we know little about the genetic background of paraneoplastic
      pemphigus (PNP) in Chinese patients. OBJECTIVES: To identify class I and class II
      HLA alleles by genotyping in Chinese patients with PNP, and to find out the
      possible association between HLA alleles and disease susceptibility. METHODS:
      Nineteen Chinese patients with PNP were enrolled in this study. HLA-A, B, C, DRB1
      and DQB1 alleles were typed by polymerase chain reaction and a colour-coded
      sequence-specific oligonucleotide probes method. RESULTS: The frequencies of HLA
      B*4002/B*4004, B*51, B*52, Cw*14, DQB1*0301, DRB1*08 and DRB1*11 were relatively
      prevalent in Chinese Han patients with PNP in comparison with normal controls.
      After correction for multiple comparisons, Cw*14 remained statistically
      significant, and the other alleles were unremarkable in these patients.
      CONCLUSIONS: The genetic background predisposing to PNP may be different in
      patients from various races and areas. HLA-Cw*14 may be the predisposing allele
      to PNP in Chinese patients, which is different from the predisposing allele in
      French patients with PNP and the alleles predisposing to pemphigus vulgaris and
      pemphigus foliaceus.

PMID- 18070208
TI  - Loss of CDKN2A and p14ARF expression occurs frequently in human nonmelanoma skin
      cancers.
AB  - BACKGROUND: The CDKN2A locus on human chromosome 9p21 encodes two proteins named
      p16INK4a and p14ARF, known to function as tumour suppressors via the
      retinoblastoma (Rb) or the p53 pathway. The p53 tumour suppressor gene is the
      most commonly mutated gene in human and mouse cancers. Disruption of the p53 and
      Rb pathways is a fundamental trend of most human cancer cells. Recent studies
      have shown that the CDKN2A gene plays an active role in the p53 and Rb tumour
      suppressor pathways. Genetic abnormalities in CDKN2A have been well documented in
      human melanoma, but their involvement in nonmelanoma skin cancer (NMSC) is less
      clear. OBJECTIVES: To determine whether genetic abnormalities in CDKN2A and p53
      genes play a role in the development of NMSC. METHODS: We analysed 40 primary
      NMSCs in 40 patients (21 squamous cell carcinomas, 17 basal cell carcinomas and
      two actinic keratoses) for p16INK4a and p14ARF protein expression and for genetic
      alterations in exons 1alpha, 1beta and 2 of CDKN2A. RESULTS: Immunohistochemical
      analysis revealed loss of expression of p16INK4a and p14ARF proteins in 38 and 39
      of 40 NMSCs, respectively. Amplification of genomic DNA by polymerase chain
      reaction revealed homozygous deletion of exon 1beta in 20% of tumours and of exon
      2 in 82.5% of tumours. Of 22 NMSCs with p53 mutations, 13 (59%) had ultraviolet
      (UV) signature mutations in the p53 gene; all of them were strongly positive for
      p53 immunostaining. CONCLUSIONS: In addition to mutations in the p53 gene, loss
      of expression of CDKN2A via deletion also plays an important role in the
      pathogenesis of human NMSC. While p53 mutations are induced by UVB, deletions in
      CDKN2A could arise spontaneously, perhaps during tumour progression.

PMID- 18070209
TI  - Functional characterization of CD4+CD25+ regulatory T cells differentiated in
      vitro from bone marrow-derived haematopoietic cells of psoriasis patients with a
      family history of the disorder.
AB  - BACKGROUND: In psoriasis CD4+CD25+ regulatory T cells are functionally deficient.
      The imbalance between regulatory and effector T-cell functions is important for
      inducing psoriasis. It is reasonable to speculate that the dysfunctional activity
      of CD4+CD25+ regulatory cells may originate partly from the abnormal
      haematopoietic cells determined mainly by genetic background. OBJECTIVES: To test
      the hypothesis that haematopoietic stem cells are responsible for dysfunctional
      CD4+CD25+ regulatory cells in psoriasis. METHODS: Bone marrow-derived CD34+
      haematopoietic cells from patients with psoriasis (with a family history of
      psoriasis) and from normal controls were differentiated into T cells in vitro.
      CD4+CD25+ T cells were isolated by an immunomagnetic bead method, and
      proliferation activity and capacity for cytokine secretion were determined.
      Furthermore, the ability of CD4+CD25+ T cells to suppress the proliferative
      responses of allogeneous peripheral blood CD4+CD25- effector T cells was assessed
      in vitro. RESULTS: The differentiated CD4+CD25+ T cells of psoriatic origin
      showed similar characteristics to those of normal volunteers, including
      proliferation activity and secretion profile of the cytokines interleukin (IL)-2,
      IL-4, IL-8, IL-10 and interferon (IFN)-gamma. However, proliferation and
      secretion levels of the cytokines IL-2 and IL-10 for CD4+CD25+ cells of psoriatic
      CD34+ cell origin were significantly lower than those of normal controls in
      response to streptococcal superantigen (Strep-A). In particular, CD4+CD25+ T
      cells differentiated from psoriatic CD34+ cells were functionally insufficient to
      restrain effector T-cell proliferation. CONCLUSIONS: CD4+CD25+ T cells
      differentiated in vitro from haematopoietic cells of patients with psoriasis are
      impaired in regulatory function. The dysfunction of psoriatic CD4+CD25+ T cells
      may be due to inherent genetic programming passed down from bone marrow-derived
      haematopoietic cells.

PMID- 18070210
TI  - Treatment of severe pemphigus with protein A immunoadsorption, rituximab and
      intravenous immunoglobulins.
AB  - BACKGROUND: Pemphigus is a life-threatening autoimmune blistering disease usually
      treated with high-dose corticosteroids and other immunosuppressants. However,
      this regimen may prove inadequate in severe cases and cause dangerous side
      effects. While protein A immunoadsorption (PAIA) induces a rapid remission in
      severe pemphigus, the disease usually recurs once the treatment is stopped. In
      contrast, anti-CD20 antibody rituximab has a delayed onset of action but may lead
      to a long-term remission of pemphigus. OBJECTIVE: To develop a treatment protocol
      combining the rapid remission induced by PAIA with the positive long-term effects
      of rituximab. PATIENTS AND METHODS: Five patients with pemphigus vulgaris and two
      patients with pemphigus foliaceus were treated with a combination of PAIA,
      rituximab and conventional immunosuppressants. Patients who failed to respond to
      this therapy subsequently received intravenous immunoglobulins (IVIg). RESULTS:
      All seven patients showed a sharp decline of circulating autoantibody levels and
      rapid improvement of cutaneous and mucosal lesions within 4 weeks of therapy.
      Long-term remission was induced in three patients and one further patient showed
      a partial improvement of his disease. The three remaining patients who could not
      be weaned off PAIA and remained resistant to rituximab treatment showed a good
      response to IVIg therapy. CONCLUSION: The combination of PAIA and rituximab
      induces a rapid and durable remission in a subset of patients with severe
      pemphigus. IVIg therapy appears to be a good treatment option for rituximab
      nonresponders.

PMID- 18070211
TI  - Hand-foot skin reaction in patients treated with sorafenib: a clinicopathological
      study of cutaneous manifestations due to multitargeted kinase inhibitor therapy.
AB  - BACKGROUND: Hand-foot skin reaction is a distinctive cutaneous side-effect of
      antineoplastic kinase inhibitor-targeted therapy. Severe hand-foot skin reaction
      requires postponement of treatment or dose reduction. Histopathological studies
      of skin toxicity associated with kinase inhibitors are currently unavailable.
      OBJECTIVES: To report the clinical and histopathological findings of hand-foot
      skin reaction produced by the multikinase inhibitor sorafenib. METHODS: Nine
      patients with metastatic carcinoma-seven with renal cell carcinoma (RCC), one
      with melanoma and one with hepatocellular carcinoma (HCC)-received continuous,
      oral sorafenib 400 mg twice daily. Hand-foot skin reaction was defined and graded
      according to National Cancer Institute Common Toxicity Criteria 3.0. Biopsies
      from lesions of erythematous scaly or blistering skin were obtained from five
      cases (four RCC and one HCC). RESULTS: Seven of the nine (78%) patients developed
      hand-foot skin reaction characterized by well-demarcated, tender, erythematous
      papules and plaques with greyish blisters or hyperkeratotic, callus-like
      formations on palmoplantar surfaces and distal phalanges. Skin biopsy of hand
      foot skin reaction lesions revealed epidermal acanthosis, papillomatosis,
      parakeratosis, dispersed dyskeratotic cells and keratinocyte vacuolar
      degeneration. Other skin toxicities included angular cheilitis, seborrhoeic
      dermatitis and perianal dermatitis. CONCLUSIONS: The clinical manifestations and
      histopathological features of sorafenib-induced skin reactions are unique. The
      most relevant histopathological findings of hand-foot skin reaction include
      keratinocyte vacuolar degeneration, the presence of intracytoplasmic eosinophilic
      bodies, and intraepidermal blisters in the stratum malpighii. Further studies are
      warranted to elucidate the mechanisms of this novel multitargeted kinase
      inhibitor-associated skin reaction.

PMID- 18070212
TI  - Cervicovaginal involvement in pemphigus vulgaris: a clinical study of 77 cases.
AB  - BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune blistering disease which is
      known to involve the female genital tract, but the frequency at which this occurs
      is unknown. There are few reports in the literature of the cytological appearance
      of PV on cervicovaginal smears. OBJECTIVES: To evaluate involvement of the female
      genital tract and the appearance of cervicovaginal Papanicolaou (Pap) smears in
      PV. METHODS: The study included 77 patients with PV who attended between April
      2005 and February 2007. Each patient was subjected to gynaecological examination
      and cervicovaginal Pap smear. RESULTS: Genital lesions were observed in 39
      patients (51%). Of these, the labia minora were involved in 36 patients (92%),
      the labia majora in 11 (28%), the vagina in 14 (36%) and the cervix in six (15%).
      Cervicovaginal Pap smears of 20 of 77 patients (26%) showed PV. Of 72
      satisfactory Pap smears, the cervical Pap smear was normal in 25 patients (35%),
      inflammatory in 43 patients (60%), and dysplastic (low-grade squamous
      intraepithelial neoplasia) in four patients (6%). CONCLUSIONS: Involvement of the
      female genital tract with PV might not be as infrequent as was previously
      thought; it is probably the second most common mucosal site of PV after the oral
      mucosa. Genital lesions may be missed and the need for thorough pelvic
      examination should not be overlooked.

PMID- 18070213
TI  - Ichthyosiform erythroderma with rickets: report of five cases.
AB  - We describe five children with ichthyosis and rickets. The association of
      ichthyosis and rickets is very rare. Four children had lamellar ichthyosis and
      one child had nonbullous ichthyosiform erythroderma/psoriasis with atopy. All had
      biochemical and radiological evidence of rickets. Three had clinically evident
      rickets, of whom two had very severe skeletal deformities. Such a severe skeletal
      involvement due to rickets in association with ichthyosis is exceptionally rare.
      We suggest that children with severe ichthyosis, in particular those with
      pigmented skin, need to be evaluated for rickets, especially in developing
      countries where there is a background prevalence of vitamin D deficiency.

PMID- 18070214
TI  - Assessment of health state utilities of controlled and uncontrolled psoriasis and
      atopic eczema: a population-based study.
AB  - BACKGROUND: Health utilities are used to express relevant trade-offs for resource
      allocation. The absence of valid and generalizable utilities for atopic eczema
      (AE) and psoriasis limits the validity of previous cost-utility analyses.
      OBJECTIVES: (i) To assess health utilities of standardized scenarios of
      controlled and uncontrolled AE and psoriasis in participants from the general
      population and in patients using the time trade-off (TTO) method; (ii) to test
      the association of the utilities obtained with demographic and patient
      characteristics; and (iii) to compare these utilities with other health economic
      outcomes [utilities assessed on visual analogue scale (VAS), willingness to pay
      (WTP)]. METHODS: A single-centre study conducted in 2006 at the Department of
      Dermatology, Dresden, Germany. Standardized interactive computer-assisted
      interviews in a random sample from the general population (n=139), and patients
      with AE (n=58) and psoriasis (n=62). Information on health states included
      characteristic clinical pictures and a short text explaining aetiology, signs,
      symptoms and quality of life impact. RESULTS: In participants from the general
      population median utilities (TTO) of controlled and uncontrolled AE were 0.97 and
      0.64, respectively. For psoriasis the corresponding utilities were 0.93 and 0.56.
      Utilities were independent of sex and socioeconomic position, and tended to be
      lower in patients with psoriasis. Correlations between TTO, VAS and WTP responses
      were weak. CONCLUSIONS: To avoid uncontrolled psoriasis or eczema participants
      chose an approximately 40% shorter life expectancy. This indicates that severe
      chronic inflammatory skin diseases may be considered as severe as angina
      pectoris, chronic anxiety, rheumatoid arthritis, multiple sclerosis or regional
      oesophageal cancer. The different economic outcomes assessed are not
      interchangeable.

PMID- 18070215
TI  - The role of hair follicles in the percutaneous absorption of caffeine.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * In recent years, it has been
      suggested that hair follicles represent important shunt routes into the skin for
      drugs and chemicals [1-3]. * In vitro studies have shown the importance of skin
      appendages for skin penetration by hydrophilic compounds [4]. Investigation of
      follicular penetration in vivo has been difficult due to the absence of
      appropriate analytical methods or suitable animal model systems. * Recently, a
      new method was described that quantifies follicular penetration in vivo by using
      selective closure of hair follicles [5]. * Caffeine is frequently used in skin
      penetration experiments as a model for highly water-soluble compounds. Occlusion
      [6] and skin thickness [7] seem to have little influence on the penetration of
      caffeine. However, percutaneous absorption rates for caffeine exhibit regional
      skin differences in humans in vivo[1]. WHAT THIS STUDY ADDS: * The results of the
      present study demonstrate that a fast drug delivery of caffeine occurs through
      shunt routes. Therefore, hair follicles are considerable weak spots in our
      protective sheath against penetration into the body by hydrophilic substances. *
      We showed that there is a quantitative distinction between follicular penetration
      and interfollicular diffusion of caffeine in vivo. * These findings are of
      importance for the development and optimization of topically applied drugs and
      cosmetics. In addition, such properties must be considered in the development of
      skin protection measures. AIMS: The skin and its appendages are our protective
      shield against the environment and are necessary for the maintenance of
      homeostasis. Hypotheses concerning the penetration of substances into the skin
      have assumed diffusion through the lipid domains of the stratum corneum. It is
      believed that while hair follicles represent a weakness in the shield, they play
      a subordinate role in the percutaneous penetration processes. Previous
      investigation of follicular penetration has mostly addressed methodical and
      technical problems. Our study utilized a selective closure technique of hair
      follicle orifices in vivo, for the comparison of interfollicular and follicular
      absorption rates of caffeine in humans. METHODS: Every single hair follicle
      within a delimited area of skin was blocked with a microdrop of a special varnish
      wax-mixture in vivo. Caffeine in solution was topically applied and
      transcutaneous absorption into the blood was measured by a new surface ionization
      mass spectrometry (SI/MS) technique, which enabled a clear distinction to be made
      between interfollicular and follicular penetration of a topically applied
      substance. RESULTS: Caffeine (3.75 ng ml(-1)) was detected in blood samples, 5
      min after topical application, when the follicles remained open. When the
      follicles were blocked, caffeine was detectable after 20 min (2.45 ng ml(-1)).
      Highest values (11.75 ng caffeine ml(-1)) were found 1 h after application when
      the follicles were open. CONCLUSIONS: Our findings demonstrate that hair
      follicles are considerable weak spots in our protective sheath against certain
      hydrophilic drugs and may allow a fast delivery of topically applied substances.

PMID- 18070216
TI  - Incidence of fatal adverse drug reactions: a population based study.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Although drugs generally are safe and
      effective therapies for numerous diseases, adverse drug reactions do occur and
      may even be fatal. * The incidence of fatal adverse drug reactions in
      hospitalized patients has been estimated to be approximately 5%. * In previous
      studies the incidence of fatal adverse drug reactions in hospitalized patients
      has been reported, but the incidence of fatal adverse drug reactions in the
      general population is largely unknown. WHAT THIS STUDY ADDS: * Fatal adverse drug
      reactions account for approximately 3% of all deaths in the general population. *
      Haemorrhages amount to almost two-thirds of the fatal adverse drug reactions and
      antithrombotic agents are implicated in more than half of the suspected fatal
      adverse drug reactions. * Fatal adverse drug reactions are estimated to be the
      seventh most common cause of death in Sweden. AIMS: To determine the incidence of
      fatal adverse drug reactions (FADRs) in a Swedish population. METHODS: Every
      seventh randomly selected deceased in three counties in South-east Sweden during
      1 January 2001-31 December 2001 was identified in the Cause of Death Register.
      Relevant case records (hospitals and/or primary care centres and medicolegal
      files) were reviewed to identify suspected drug-related fatalities. RESULTS: Of
      1574 deceased study subjects, 49 (3.1%; 95% CI 2.2%, 4.0%) were suspected to have
      died from FADRs. The most common suspected FADRs were gastrointestinal
      haemorrhages (n = 18; 37%), central nervous system haemorrhages (n = 14; 29%),
      cardiovascular disorders (n = 5; 10%), other haemorrhages (n = 4; 8%) and renal
      dysfunction (n = 3; 6%). The drugs most commonly implicated in FADRs were
      antithrombotic drugs (n = 31; 63%), followed by nonsteroidal anti-inflammatory
      drugs (NSAIDs) (n = 9; 18%), antidepressants (n = 7; 14%) and cardiovascular
      drugs (n = 4; 8%). Of all the 639 fatalities in hospital 41 (6.4%; 95% CI 4.5%,
      8.3%) were suspected to be due to FADRs. CONCLUSIONS: The medical burden of FADRs
      is significant. Haemorrhages were seen in a majority of the FADRs; antithrombotic
      agents or NSAIDs were implicated in most of these events. These results suggest
      that preventive measures should be taken to reduce the number of deaths caused by
      drugs.

PMID- 18070217
TI  - In vivo visualization of donepezil binding in the brain of patients with
      Alzheimer's disease.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Deficit in central cholinergic
      neurotransmission is a consistent change associated with Alzheimer's disease
      (AD). * Donepezil hydrochloride exhibits selective inhibition of
      acetylcholinesterase (AChE) and is widely used for the treatment of AD. * The
      biodistribution of donepezil in the brain after administration is not precisely
      understood in vivo. * There is no method to measure the amount of binding of
      orally administered donepezil to AChE. WHAT THIS STUDY ADDS: * This study clearly
      visualizes the distribution of donepezil in human brain using [(11)C]-donepezil
      and positron emission tomography. * This study demonstrates prominent reduction
      of the donepezil binding site in the AD brain. * This study provides methodology
      to measure the AChE binding occupancy of orally administered donepezil and
      provides a new surrogate marker for evaluation and prediction of response to
      donepezil treatment. AIMS: The aims of this study were to visualize in vivo
      binding of donepezil to acetylcholinesterase (AChE) in the brain and to establish
      a method for measuring the amount of binding of orally administered donepezil.
      METHODS: [5-(11)C-methoxy]-donepezil ([(11)C]-donepezil) was radiolabelled as a
      positron emission tomography (PET) tracer. The biodistribution of [(11)C]
      donepezil was measured by PET in 10 AD patients and six elderly normal subjects.
      Two AD patients underwent additional PET measurements after oral administration
      of donepezil for 6 months. RESULTS: [(11)C]-donepezil-PET images demonstrated
      high densities of tracer distribution in AChE-rich brain regions such as the
      striatum, thalamus, and cerebellum. Compared with elderly normal subjects,
      patients with mild AD exhibited about 18-20% reduction of donepezil binding in
      the neocortex and hippocampus, while patients with moderate AD exhibited about 24
      30% reduction of donepezil binding throughout the brain. Orally administered
      donepezil (5 mg day(-1)) induced 61.6-63.3% reduction of donepezil binding in AD
      brains. The distribution volume of [(11)C]-donepezil in the hippocampus was
      significantly correlated with MMSE scores in AD patients. CONCLUSIONS: [(11)C]
      donepezil-PET enables quantitative measurement of donepezil binding in the brain.
      AD patients exhibited reduction of donepezil binding in the brain, even in the
      early stage of disease. Longitudinal evaluation by this technique enables
      determination of AChE binding occupancy of orally administered donepezil.

PMID- 18070218
TI  - Drug-induced liver graft toxicity caused by cytochrome P450 poor metabolism.
AB  - What is already known about this subject. The activity of drug-metabolizing
      enzymes, primarily cytochrome P450 enzymes, can determine a patient's response to
      a drug. Therapeutic failure or drug toxicity in the postoperative period after
      liver transplantation is influenced by the drug metabolizing capacity of the
      graft. Dose adjustment or selection of an alternative drug, which is not a
      substrate for the polymorphic enzyme may prevent the development of side-effects
      in recipients of poor metabolizer liver grafts. What this study adds. A validated
      analytical system with metabolomic tools has been developed to estimate the drug
      metabolizing capacity of transplanted liver, which allows the prediction of
      potential poor metabolizer phenotypes of donors and facilitates the improvement
      of individual recipient therapy. In the test of drug-metabolizing status, one of
      the liver grafts was found to be a CYP2C9 poor metabolizer, while the other was a
      CYP2C19 poor metabolizer. Rationalization of the medication resulted in the
      recovery of both the grafts and the recipients within 1 week. AIMS: The drug
      metabolizing capacity of transplanted liver highly influences drug efficacy or
      toxicity, particularly in the early postoperative period. The aim of our study
      was to predict therapeutic failures or severe adverse drug reactions by
      phenotyping for cytochrome P450 (P450) polymorphism resulting in reduced or no
      activity of the key drug-metabolizing enzymes. METHODS: A validated analytical
      system with metabolomic tools has been developed for estimation of the drug
      metabolizing capacity of transplanted liver, which allows the prediction of
      potential poor metabolizer phenotypes of donors and facilitates improvement of
      the individual recipient therapy. RESULTS: Of the 109 liver donors in Hungary,
      the frequency of poor metabolizers was found to be 0.92%, 5.5% and 8.3% for
      CYP2C9, CYP2C19 and CYP2D6, respectively. In the present study, two liver grafts
      transplanted in paediatric recipients were reported to be poor metabolizer
      phenotypes. The liver grafts presented normal function in the early postoperative
      days; 2 weeks after transplantation, however, increasing liver enzymes were
      detected. Histological investigation of a liver biopsy suggested drug toxicity.
      The test of drug metabolizing status showed one of the liver grafts to be a
      CYP2C9 poor metabolizer, and the other was found to be a CYP2C19 poor
      metabolizer. Rationalization of the medication resulted in the recovery of both
      the grafts and the recipients within 1 week. CONCLUSIONS: Prospective
      investigation of the P450 status may lead to the optimization of drug choice
      and/or dose for a more effective therapy, avoid serious adverse effects, and
      decrease medical costs. Phenotyping donor livers and tailored medication can
      contribute to the improvement of graft and recipient survival.

PMID- 18070219
TI  - Clinical uses of interferons.
AB  - Interferons were first described by Isaacs & Lindenmann working at the National
      Institute for Medical Research, Mill Hill in 1957. Thus, the fiftieth year of
      their discovery is being celebrated this year at Oxford in a meeting of the
      International Society for Interferon and Cytokine Research. This then is an
      appropriate time to review the clinical applications of the interferons. To
      accomplish this coherently it is necessary also to review briefly what led to the
      discovery of interferons, why their clinical applications were so slow in coming,
      and the impact of interferon research on the biomedical sciences.

PMID- 18070221
TI  - Influence of the CYP2D6*4 polymorphism on dose, switching and discontinuation of
      antidepressants.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Most antidepressants are metabolized
      by CYP2D6. The variant allele CYP2D6*4 is the main polymorphism resulting in
      reduced enzyme activity in Caucasians. * Reduced enzyme activity potentially
      leads to increased toxicity of antidepressants, but the relevance of genotyping
      for clinical practice is unclear. Most clinical studies suffer from small numbers
      of patients. WHAT THIS STUDY ADDS: * This large population-based cohort study in
      1198 elderly Dutch patients examines the influence of the CYP2D6*4 polymorphism
      on intolerability of antidepressants. * The risk of switching to another
      antidepressant in tricyclic antidepressant users is higher in poor metabolizers
      (PMs), but not in SSRI users. PMs require a lower maintenance dose of
      antidepressants compared with extensive metabolizers (EMs). * Antidepressants
      were initiated in a relatively low dose, with gradual dose increments thereafter,
      reducing the risk of adverse drug reactions. Therefore, the question remains
      whether genotyping prior to the start of antidepressant therapy contributes
      substantially to the optimization of pharmacotherapy. AIMS: To study the effect
      of CYP2D6*4 on antidepressant dose, switching and discontinuation of therapy.
      METHODS: The study consisted of all subjects in the Rotterdam Study, who received
      a first antidepressant prescription between April 1st 1991 and July 1st 2005 and
      for whom data on CYP2D6 genotype were available. Binary logistic regression was
      performed to study the association between CYP2D6*4 and switching to any other
      antidepressant or discontinuation of therapy within 45 days. The difference in
      mean antidepressant dose was compared between CYP2D6 genotypes using t-tests and
      repeated measurements analyses. RESULTS: In users of tricyclic antidepressants
      (TCAs) the risk of switching to another antidepressant was significantly higher
      in poor metabolizers (PMs:*4/*4) compared with extensive metabolizers
      (EMs:*1/*1), with an adjusted OR of 5.77 (95% CI 1.59, 21.03; P = 0.01). In SSRI
      users there was no significant difference (OR 0.91; 95% CI 0.20, 4.15; P = 0.90).
      Heterozygous patients did not have an increased risk of switching in both TCA and
      SSRI users. The mean TCA dose was significantly lower in PMs than in EMs at the
      third and fourth prescription (difference 0.11 DDD, P = 0.03). In SSRI users the
      difference in mean dose between PMs and EMs was significant at the third
      prescription (0.17 DDD; P = 0.02). CONCLUSIONS: The risk of switching to another
      antidepressant in TCA users is higher in PMs than in EMs. The maintenance doses
      of antidepressants were significantly lower in PMs. However, the question whether
      genotyping prior to the start of antidepressant therapy contributes substantially
      to the optimization of pharmacotherapy, requires further study.

PMID- 18070223
TI  - Adverse drug reactions in adult medical inpatients in a South African hospital
      serving a community with a high HIV/AIDS prevalence: prospective observational
      study.
AB  - What is already known about this subject. Studies conducted primarily in
      developed countries have shown that adverse drug reactions (ADRs) are a
      significant cause of hospital admission, prolong hospital stay and consequently
      increase the cost of disease management in patients. Cardiovascular medicines,
      hypoglycaemic agents, nonsteroidal anti-inflammatory drugs and antibiotics are
      the most frequently implicated medicines in these studies. A large proportion of
      these ADRs have been shown to be preventable through improved drug prescribing,
      administration and monitoring for adverse effects. What this paper adds. This is
      the first Sub-Saharan African study in the HIV/AIDS era that describes the
      contribution of ADRs to patient morbidity, hospitalisation and mortality.
      Cardiovascular medicines and antiretroviral therapy contributed the most to
      community-acquired ADRs at the time of hospital admission while medicines used
      for opportunistic infections (such as antifungals, antibiotics and
      antituberculosis medicines were most frequently implicated in hospital acquired
      ADRs. ADRs in HIV-infected patients were less likely to be preventable. AIMS: To
      describe the frequency, nature and preventability of community-acquired and
      hospital-acquired adverse drug reactions (ADRs) in a South African hospital
      serving a community with a high prevalence of human immunodeficiency virus (HIV)/
      acquired immunodeficiency syndrome. METHODS: A 3-month prospective observational
      study of 665 adults admitted to two medical wards. RESULTS: Forty-one (6.3%)
      patients were admitted as a result of an ADR and 41 (6.3%) developed an ADR in
      hospital. Many of the ADRs (46.2%) were considered preventable, although less
      likely to be preventable in HIV-infected patients than in those with negative or
      unknown HIV status (community-acquired ADRs 2/24 vs. 35/42; P < 0.0001; hospital
      acquired ADRs 3/25 vs. 14/26; P = 0.003). Patients admitted with ADRs were older
      than patients not admitted with an ADR (median 53 vs. 42 years, P = 0.003), but
      60% of community-acquired ADRs at hospital admission were in patients <60 years
      old. Among patients <60 years old, those HIV infected were more likely to be
      admitted with an ADR [odds ratio (OR) 2.32, 95% confidence interval (CI) 1.17,
      4.61; P = 0.017]. Among HIV-infected patients, those receiving antiretroviral
      therapy (ART) were more likely to be admitted with an ADR than those not
      receiving ART (OR 10.34, 95% CI 4.50, 23.77; P < 0.0001). No ART-related ADRs
      were fatal. Antibiotics and drugs used for opportunistic infections were
      implicated in two-thirds of hospital-acquired ADRs. CONCLUSIONS: ADRs are an
      important, often preventable cause of hospitalizations and inpatient morbidity in
      South Africa, particularly among the elderly and HIV-infected. Although ART
      related injury contributed to hospital admissions, many HIV-related admissions
      were among patients not receiving ART, and many ADRs were associated with
      medicines used for managing opportunistic infections.

PMID- 18070224
TI  - Age-dependent normative values for differential luminance sensitivity in
      automated static perimetry using the Octopus 101.
AB  - PURPOSE: To determine age-dependent normative differential threshold values for
      the Octopus 101 instrument and to create a smooth mathematical model
      characterizing the age-dependency and asymmetry of the hill of vision. METHODS:
      Static automated perimetry within the central 30 degrees visual field (VF) was
      conducted with the Octopus 101 (background luminance 10 cd/m(2)) in 81 eyes of 81
      ophthalmologically healthy subjects (11-12 per decade of age) aged 10-79 years. A
      4-2-2 staircase strategy with three reversals was run. The test point grid
      consisted of 68 concentrically arranged points with test point condensation
      towards the VF centre, representing the approximately rotation-symmetrical 30
      degrees hill of vision. Thresholds of differential luminance sensitivity (DLS)
      were estimated by the maximum likelihood method. A smooth mathematical model was
      fitted to the normative data. RESULTS: The model fit was satisfactory (r(2) =
      0.74). Covariables were: age, eccentricity, angle and subject. Total random
      standard deviation (SD) was 1.75 dB. The residual SD exceeded 1.75 dB in the
      border region, was 1.5 dB within the centre and fell below 1.25 dB in a ring
      around the centre. Average thresholds of DLS varied with age quadratically. It is
      close to constant for the 10-40-year-old age group and declines ever more steeply
      thereafter. The effect of age on DLS in the VF increased with eccentricity. The
      greatest drop was located in the peripheral superior hemifield: at 25 degrees
      eccentricity the superior DLS was estimated to be 5.5 dB higher in 10-year-olds
      than in 75-year-olds. CONCLUSIONS: This new smooth model allows for the
      prediction of age-related normal threshold values for any stimulus location
      within the 30 degrees VF and thus for the calculation of global and local
      measures of defect such as mean defects or p-values for any type of stimulus.

PMID- 18070225
TI  - Electrophysiological changes associated with optic nerve compression caused by
      the distension of orbital varices.

PMID- 18070226
TI  - Investigation of auditory dysfunction in Leber hereditary optic neuropathy.
AB  - PURPOSE: To investigate the possibility of auditory dysfunction in patients with
      Leber hereditary optic neuropathy (LHON). METHODS: We prospectively recruited 10
      affected patients from the north-east of England harbouring one of the three
      primary mitochondrial LHON mutations (3460G>A n = 3, 11778G>A n = 5 and 14484T>C
      n = 2). A detailed auditory history was taken and they were asked to complete a
      validated hearing questionnaire. Each patient then underwent a comprehensive
      topographic neuroauditory assessment to evaluate both middle- and inner-ear
      functions and the integrity of the brainstem auditory pathways. RESULTS: We found
      no evidence of cochlear nerve dysfunction or abnormalities of the central
      brainstem auditory pathways in our LHON cohort and five patients had completely
      normal hearing tests. The remainder had mild conductive hearing loss from
      childhood ear infections and/or high-frequency sensorineural hearing loss from
      previous noise injury. CONCLUSION: Although further studies are required to
      confirm our findings, auditory dysfunction as a result of a primary LHON mutation
      is probably uncommon.

PMID- 18070227
TI  - Functional in vivo assessment of retinal artery microirregularities in glaucoma.
AB  - PURPOSE: We investigated whether retinal branch arteries in healthy subjects, and
      non-treated and treated primary open-angle glaucoma (POAG) patients show
      irregular local patterns during dynamic reaction to acute increases of different
      magnitudes in intraocular pressure (IOP). METHODS: Nine POAG patients and nine
      age-matched normal volunteers were examined with the retinal vessel analyser
      (RVA) using a suprasystolic IOP increase (Study 1). Fourteen POAG patients and 13
      age-matched controls were examined using a moderate IOP increase for 100 seconds
      (Study 2). Longitudinal arterial profiles were obtained for the chosen time
      intervals. The high-frequency waviness (HFW) of these profiles was analysed
      quantitatively. RESULTS: No significant changes in HFW were found in controls in
      different phases of the arterial reaction. Significant increases in HFW from
      baseline to dilation (Study 1, P < 0.03) and from dilation to constriction (Study
      2, P < 0.05) were found in POAG patients. High-frequency waviness was higher in
      POAG patients than in controls during dilation (P < 0.05) in both studies.
      CONCLUSIONS: Our results indicate a local vessel wall difference in glaucoma
      patients compared with age-matched controls. Increasing HFW might worsen
      hydraulic resistance of the vessel segment to blood flow. Significant increase of
      arterial microirregularities in the POAG retina during vascular dilation might be
      an indication for vascular endothelial alterations in glaucoma, leading to
      impaired perfusion in response to IOP increase.

PMID- 18070228
TI  - Skin reactivity and local cell recruitment in human atopic and nonatopic subjects
      by CCL2/MCP-1 and CCL3/MIP-1alpha.
AB  - BACKGROUND: Monocyte chemotactic protein (MCP-1/CCL2), the ligand for CCR2 and
      CCR5, and macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3), the ligand
      for CCR1 and CCR5, are potent chemo-attractants in vitro and produce lesions in
      experimental animals, which resemble immediate and delayed-type hypersensitivity
      (DTH) reactions. CCL3 induces mononuclear cell and granulocyte infiltration in
      human atopic and nonatopic skin. Whether CCL2 (MCP-1) has comparable activity in
      man is uncertain as is the capacity of both the chemokines to elicit immediate-
      and DTH-like reactions in humans. METHODS: Inflammatory cells were counted by
      immunohistochemistry in 24 and 48-h skin biopsies from atopics and nonatopics
      after intradermal injection of CCL2 and CCL3. Immediate (15 min) wheals-and
      flares and delayed (24 and 48 h) indurations were also recorded. RESULTS: Both
      chemokines induced immediate- (15 min) and delayed (24 and 48 h) reactions, which
      were associated with significant infiltrations of CD68+ macrophages, CD3+, CD4+
      (but not CD8+) T cells, neutrophils, and eosinophils in biopsies from injection
      sites. CCL2, but not CCL3, also induced infiltration of basophils. Neither
      chemokine produced significant changes in the numbers of tryptase+ cutaneous mast
      cells. There were no differences in the pattern of skin reactivity or the numbers
      of infiltrating leukocytes in response to CCL2 and CCL3 between atopic and
      nonatopic subjects. In general, maximal infiltration of inflammatory cells was
      observed at the 24-h, rather than the 48-h, time point. CONCLUSIONS: CCL2 and
      CCL3 induce both immediate and delayed skin reactions in atopics and nonatopics,
      and evoke a similar profile of local T cell/macrophage and granulocyte
      recruitment which, in general, confirm previous in vitro findings and in vivo
      experimental animal data.

PMID- 18070229
TI  - Assessing skin prick tests reliability in ECRHS-I.
AB  - INTRODUCTION: Atopy, the clinical definition of an immunoglobulin E (IgE) high
      responder, can be documented either by the detection of IgE antibodies in serum
      or by a positive skin prick test. Epidemiological studies use different reaction
      sizes to define a skin test reaction as positive or negative. The aim of the
      study was to identify the best cut-off level for skin prick tests. METHOD: Using
      the data collected during the European Community Respiratory Health Survey (ECHRS
      I) the association of serum allergen-specific IgE and skin prick tests
      [Dermatophagoides pteronyssinus (Der p), cat, timothy grass and Cladosporium]
      were assessed. RESULTS: The proportion of the 11 355 subjects (49.9% men), with
      positive skin tests ranged from 10.4% (cut-off >5 mm) to 20.9% (cut-off >0 mm)
      for Der p, 3.5-10.2% for cat, 9.3-16.6% for timothy grass and 0.2 and 2.3% for
      Cladosporium. For identifying subjects with detectable specific IgE (>0.35 kU/l)
      the most appropriate cut-off appeared to be over 0 mm for Der p, cat and timothy
      grass (Youden Index over 0.81). However, the relationship between serum IgE and
      skin prick test for Cladosporium was weak (Youden index under 0.56). CONCLUSION:
      In epidemiological studies, a single method may be chosen to assess allergenic
      sensitivity. A cut-off level of over 0 mm for skin prick tests was best at
      identifying those with allergen-specific IgE.

PMID- 18070230
TI  - Selective blockade of NF-kappaB by novel mutated IkappaBalpha suppresses CD3/CD28
      induced activation of memory CD4+ T cells in asthma.
AB  - BACKGROUND: Nuclear factor kappaB (NF-kappaB) overactivation plays a crucial role
      in T-helper 2 (Th2)-biased allergic airway inflammation by increased activation
      and decreased apoptosis of CD4(+) T cells. We have shown that targeted NF-kappaB
      suppression in dendritic cells by adenoviral gene transfer of a novel mutated
      inhibitor of NF-kappaB (IkappaBalpha) (AdIkappaBalphaM) contributes to T-cell
      tolerance, but the immunosuppressive action of AdIkappaBalphaM on memory
      (CD45RO(+)) CD4(+) T cells remains enigmatic. METHODS: CD45RO(+) T cells from
      Dermatophagoides farinaei-sensitized asthmatic patients, untransfected or
      transfected with AdIkappaBalphaM or AdLacZ (beta-galactosidase) for 24 h, were
      stimulated with anti-CD3 (1.0 microg/ml) plus anti-CD28 (0.5 microg/ml)
      monoclonal antibody for an additional 24 h. IkappaBalphaM transgene expression
      and NF-kappaB activation were detected by polymerase chain reaction (PCR),
      reverse transcription-PCR (RT-PCR), Western blot analysis, and electrophoretic
      mobility shift assay. Phenotype and apoptosis were measured by flow cytometry,
      annexin V binding, and terminal deoxyribonucleotidyl transferase-mediated dUTP
      nick end labeling analyses. Cytokine production and cell proliferation were
      determined using enzyme-linked immunosorbent assay and [(3)H] thymidine
      incorporation. RESULTS: A unique 801-bp IkappaBalphaM cDNA and a dose-dependent
      increase in IkappaBalphaM transgene expression were observed in AdIkappaBalphaM
      transfected CD45RO(+) T cells. Significantly, AdIkappaBalphaM inhibited CD3/CD28
      mediated NF-kappaB activation in CD45RO(+) T cells, leading to evident apoptosis,
      reduction of eotaxin, RANTES, Th1 [interferon (IFN)-gamma and interleukin (IL)
      2], and Th2 (IL-4, IL-5, and IL-13 despite a slight decrease in IL-10) cytokines
      and secondary proliferative response. AdIkappaBalphaM also upregulated cytotoxic
      T lymphocyte-associated antigen 4 (CTLA-4) and downregulated CD69 besides no
      change in CD28. CONCLUSION: IkappaBalphaM might be beneficial to augment memory
      CD4(+) T-cell tolerance through modulating B7-CD28/CTLA-4 co-stimulatory pathways
      and NF-kappaB-dependent cytokine profiles in allergic inflammatory diseases
      including asthma.

PMID- 18070231
TI  - Oestrogen-dependent hereditary angio-oedema with normal C1 inhibitor: description
      of six new cases and review of pathogenic mechanisms and treatment.
AB  - BACKGROUND: Hereditary angio-oedema (HAE) is a rare condition in which there is a
      deficiency in the quantity or activity of C1 inhibitor (C1INH). Recently, an
      additional type of HAE with no alterations in the levels or the function of C1INH
      has been reported. It is defined as HAE with normal C1INH, and named type III HAE
      or oestrogen-dependent HAE. The aim of this study is to describe the clinical and
      laboratory findings of six new cases of type III HAE and to review the literature
      about this disease. METHODS: A short description of six women with recurrent
      angio-oedema is provided. The characteristics of the patients are compared with
      the previously reported case series in a literature-based review. RESULTS: The
      mean age of the patients at onset was 22 years (range 16-30). All of them had
      angio-oedema attacks during oestrogen-based contraceptive treatment and four
      reported episodes during pregnancy. Four patients reported a positive past family
      history. Two of them had experienced episodes of laryngeal oedema. None of the
      patients responded to corticoids or antihistamines during the attacks. Levels and
      functional activity of C1INH were within the normal range in all cases.
      CONCLUSIONS: Clinical and laboratory findings mirror the observations of previous
      reports of oestrogen-dependent angio-oedema with normal C1INH. This is the first
      published series of type III HAE in Spain.

PMID- 18070233
TI  - In patients with slow transit constipation, the pattern of colonic transit delay
      does not differentiate between those with and without impaired rectal evacuation.
AB  - BACKGROUND: Severe constipation may be subclassified on the basis of speed of
      colonic transit and efficacy of rectal evacuation. It is hypothesized that rectal
      evacuatory disorder (RED) may be associated with a secondary transit delay.
      OBJECTIVES: To determine whether scintigraphy can discriminate between slow
      transit constipation (STC) with or without coexistent RED on the basis of
      progression of isotope throughout the colon and by analyses of specific regions
      of interest. METHODS: One hundred ninety-six patients with STC (radio-opaque
      marker study) were subclassified according to results of proctography into those
      with a RED (STC-RED N = 30) or normal (STC-ONLY N = 41) evacuation. Patients
      subsequently underwent colonic scintigraphy. Distribution of generalized or left
      sided patterns of colonic transit was assessed. Severities of transit delay and
      regional transit at specific time points were also evaluated. RESULTS: Time
      activity curves and severity of global transit delay were similar between groups
      as were the incidences of generalized and left-sided patterns of delay.
      Percentage of radioisotope retention in the right colon at 18 h was higher for
      the STC-ONLY group (P < 0.05), but this was poorly discriminative. No differences
      were observed for the percentage of radioisotope retained in the left colon at
      later scans. CONCLUSIONS: Global and regional assessment of colonic transit by
      scintigraphy failed to discriminate between patients with STC with or without
      coexistent RED. Thus, RED is not associated with a specific pattern of transit
      delay and scintigraphy alone cannot predict the presence or absence of RED,
      knowledge of which is important for management.

PMID- 18070232
TI  - Botulinum toxin A for the treatment of delayed gastric emptying.
AB  - BACKGROUND: Observational data suggest that intrapyloric injection of botulinum
      toxin A (BoTN/A) reduces symptoms and accelerates gastric emptying in idiopathic
      and diabetic gastroparesis. Our purpose was to determine whether botulinum toxin
      improves symptoms to a significantly greater extent than placebo. An additional
      objective was to determine whether there is an acceleration of gastric emptying
      after injection. METHODS: A single-institution, randomized, double-blind, placebo
      controlled trial* was done. Eligible patients had a Gastroparesis Cardinal
      Symptom Index score > or = 27 with randomization to intrapyloric botulinum toxin,
      200 U (units), or saline placebo. Reassessment of symptoms and repeat gastric
      emptying scan at 1-month follow-up were done. RESULTS: Thirty-two patients were
      randomized to botulinum toxin (N = 16) and placebo (N = 16). At 1-month follow
      up, 37.5% randomized to botulinum toxin and 56.3% randomized to placebo achieved
      improvement as defined by this study. There were no identifiable clinical
      predictors of response. The botulinum toxin group demonstrated improvement in
      gastric emptying; however, this was not superior to placebo. No serious adverse
      events were attributable to botulinum toxin. CONCLUSIONS: Intrapyloric injection
      of botulinum toxin improves gastric emptying in patients with gastroparesis,
      although this benefit was not superior to placebo at 1 month. Also, in comparison
      to placebo, symptoms do not improve significantly by 1 month after injection.
      Overall, we are unable to recommend botulinum toxin therapy for widespread use in
      the treatment of delayed gastric emptying until more data are available.

PMID- 18070234
TI  - Computed virtual chromoendoscopy for classification of small colorectal lesions:
      a prospective comparative study.
AB  - OBJECTIVES: Standard colonoscopy offers no reliable discrimination between
      neoplastic and nonneoplastic colorectal lesions. Computed virtual chromoendoscopy
      with the Fujinon intelligent color enhancement (FICE) system is a new dyeless
      imaging technique that enhances mucosal and vascular patterns. This prospective
      trial compared the feasibility of FICE, standard colonoscopy, and conventional
      chromoendoscopy with indigo carmine in low- and high-magnification modes for
      determination of colonic lesion histology. METHODS: Sixty-three patients with 150
      flat or sessile lesions less than 20 mm in diameter were enrolled. At
      colonoscopy, each lesion was observed with six different endoscopic modalities:
      standard colonoscopy, FICE, and conventional chromoendoscopy with indigo carmine
      (0.2%) dye spraying in both low- and high-magnification modes. Histopathology of
      all lesions was confirmed by evaluation of endoscopic resection or biopsy
      specimens. Endoscopic images were stored electronically and randomly allocated to
      a blinded reader. RESULTS: Of the 150 polyps, 89 were adenomas and 61 were
      hyperplastic polyps with an average size of 7 mm. For identifying adenomas, the
      FICE system with low and high magnifications revealed a sensitivity of 89.9% and
      96.6%, specificity of 73.8% and 80.3%, and diagnostic accuracy of 83% and 90%,
      respectively. Compared with standard colonoscopy, the sensitivity and diagnostic
      accuracy achieved by FICE were significantly better under both low (P < 0.02) and
      high (P < 0.03) magnification and were comparable to that of conventional
      chromoendoscopy. CONCLUSIONS: The FICE system identified morphological details
      that efficiently predict adenomatous histology. For distinguishing neoplastic
      from nonneoplastic lesions, FICE was superior to standard colonoscopy and
      equivalent to conventional chromoendoscopy.

PMID- 18070235
TI  - The incidence of cyclic vomiting syndrome in children: population-based study.
AB  - OBJECTIVE: Cyclic vomiting syndrome (CVS) is characterized by severe recurrent
      episodes of vomiting in an otherwise healthy child. Currently, there is no
      population data on the incidence of CVS. The aim of this study was to determine
      the incidence of CVS and to define the clinical characteristics of the condition
      at diagnosis. METHODS: Each pediatrician on the island of Ireland was surveyed on
      a monthly basis from January 1, 2005 to December 31, 2005 by the Irish Pediatric
      Surveillance Unit (IPSU) and was asked to report any incident cases of CVS
      according to the criteria outlined by the First International Symposium on CVS.
      Subsequently, data on demographics and clinical features were collected
      anonymously from the reporting pediatricians. RESULTS: Eighty-nine percent (1,647
      of 1,848) of the surveillance cards were returned, reporting 41 valid cases of
      CVS. The incidence of CVS in Ireland was 3.15/100,000 children per annum for 2005
      (95% confidence interval [CI] 2.19-4.11). The median age at diagnosis of CVS was
      7.42 yr (range 1.8-15 yr). The median age at onset of CVS was 4 yr (range 0.5-14
      yr) with 46% (19 of 41) of children having an onset at or before the age of 3 yr.
      The median number of episodes of CVS per child per year was eight (range 3-52);
      the median duration of an episode was 24 h (range 1 h to 5 days). Of school-age
      children, 85% (22 of 26) had missed school in the previous year due to CVS and
      44% (18 of 41) were admitted to hospital for supportive treatment or
      investigation of CVS. CONCLUSION: CVS is a relatively common condition in
      pediatric patients, with an incidence comparable to other major gastrointestinal
      diseases of childhood, such as Crohn's disease. The onset of pediatric CVS is
      generally early in childhood and this disease causes significant morbidity in the
      majority of those affected.

PMID- 18070236
TI  - Reduction of interstitial cells of Cajal (ICC) associated with neuronal nitric
      oxide synthase (n-NOS) in patients with achalasia.
AB  - BACKGROUND: The etiology of achalasia is still unknown. The current theories of
      chronic inflammation leading to autoimmune response with destruction and loss of
      the inhibitory myenteric ganglion cells enlighten its pathogenesis in a limited
      way only. Interstitial cells of Cajal (ICC) have been shown to be involved in
      nitrergic neurotransmission of the lower esophageal sphincter (LES). AIM: To
      investigate the significance of ICC and neuronal nitric oxide synthase (n-NOS) in
      esophageal wall tissue of patients undergoing surgery for achalasia. METHODS: In
      53 patients with a median age of 45 (6-78) yr undergoing surgery for achalasia,
      the immunoreactivity of ICC (CD117/c-kit) and n-NOS was assessed. In 42 patients,
      biopsies were taken from the LES high-pressure zone during Heller myotomy,
      whereas in 11 patients with end-stage achalasia and a decompensated
      megaesophagus, the complete esophagus was resected. A semiquantitative analysis
      was carried out and ICC and n-NOS impairments were classified into four grades.
      Staining intensity was correlated with preoperative clinical, radiologic, and
      manometric findings and with long-term postoperative Eckardt score. RESULTS:
      Grade III/IV ICC reduction (severe reduction to complete loss) was seen in 59.5%
      of all biopsy specimens of the LES high-pressure zone. Patients with grade III/IV
      ICC reduction had a significantly longer duration of achalasia symptoms (3 [0-43]
      yr) than patients with minor to marked (grade I/II) impairment (1 [0-16] yr, P=
      0.028). A majority (72.5%) of tissue samples revealed severe reduction to
      complete loss of n-NOS immunoreactivity. The preoperative Eckardt score was
      statistically significantly different between patients with grade I/II and those
      with grade III/IV n-NOS reductions (P= 0.031). CD117 (c-kit) positivity was
      statistically significantly correlated with n-NOS staining intensity (correlation
      coefficient r= 0.781, P < 0.0001). CONCLUSION: The present results suggest that
      in the pathogenesis of achalasia, especially in the development of the LES high
      pressure zone, depletion of ICC networks and potential changes in the electrical
      activity of smooth muscle cells may play a crucial role. The reduction in CD117
      positive ICC in a few patients also seemed to be of relevance, even if the cells
      of Auerbach's plexus were unscathed. The associated reduced NOS release might
      underlie the profound ICC impairment and could possibly be responsible for the
      lack of LES relaxation, because of missing inhibitory neurotransmission. It is
      unclear, however, whether the ICC loss is primarily caused by the accelerated
      attrition of mature cells or their impaired regeneration.

PMID- 18070237
TI  - Proton pump inhibitors and the risk of colorectal cancer.
AB  - INTRODUCTION: Proton pump inhibitor (PPI) use is associated with increased serum
      gastrin levels and bacterial overgrowth, resulting in more toxic bile salt
      formation. Concern has risen that these factors may increase the risk of
      developing colorectal neoplasia. AIM: To investigate the association between the
      use of PPIs and the risk of colorectal cancer. METHODS: A population-based case
      control study was conducted within the Dutch Primary Care Information (IPCI)
      database over the period 1996-2005. Cases with colorectal cancer were matched
      with up to 20 controls on age, gender, calendar time, and duration of follow-up
      prior to diagnosis. Cumulative exposure to PPIs was assessed in the 5 yr prior to
      diagnosis with a 1-yr lag time analysis. We calculated adjusted odds ratios (OR)
      with 95% confidence intervals (95% CI) using multivariate, conditional logistic
      regression analysis. RESULTS: Within the source population of 457,024 persons, we
      identified 595 colorectal cancer cases. The odds of colorectal cancer were not
      increased among patients ever using PPIs compared with patients who never used
      PPIs (OR 0.85, 95% CI 0.63-1.16). Also, the use of PPIs for >365 days was not
      associated with a greater risk of colorectal cancer (OR 0.79, 95% CI 0.44-1.41)
      compared with nonusers. The odds of colorectal cancer in neither the right nor
      the left hemicolon were significantly increased in patients using PPIs.
      CONCLUSION: The present study indicates no association between PPI use and the
      risk of colorectal cancer. Larger numbers of long-term PPI users are needed to
      confirm the absence of a risk-increasing effect of long-term PPI exposure.

PMID- 18070238
TI  - UK Alcohol Treatment Trial: client-treatment matching effects.
AB  - AIM: To test a priori hypotheses concerning client-treatment matching in the
      treatment of alcohol problems and to evaluate the more general hypothesis that
      client-treatment matching adds to the overall effectiveness of treatment. DESIGN:
      Pragmatic, multi-centre, randomized controlled trial (the UK Alcohol Treatment
      Trial: UKATT) with open follow-up at 3 months after entry and blind follow-up at
      12 months. SETTING: Five treatment centres, comprising seven treatment sites,
      including National Health Service (NHS), social services and joint NHS/non
      statutory facilities. TREATMENTS: Motivational enhancement therapy and social
      behaviour and network therapy. MEASUREMENTS: Matching hypotheses were tested by
      examining interactions between client attributes and treatment types at both 3
      and 12 months follow-up using the outcome variables of percentage days abstinent,
      drinks per drinking day and scores on the Alcohol Problems Questionnaire and
      Leeds Dependence Questionnaire. FINDINGS: None of five matching hypotheses was
      confirmed at either follow-up point on any outcome variable. CONCLUSION: The
      findings strongly support the conclusion reached in Project MATCH in the United
      States that client-treatment matching, at least of the kind examined, is unlikely
      to result in substantial improvements to the effectiveness of treatment for
      alcohol problems. Possible reasons for this failure to support the general
      matching hypothesis are discussed, as are the implications of UKATT findings for
      the provision of treatment for alcohol problems in the United Kingdom.

PMID- 18070239
TI  - Expression and immunohistochemical localization of aquaporin-1 in male
      reproductive organs of the mouse.
AB  - Aquaporin-1 (AQP-1), a six-transmembrane domain protein, is found to be
      responsible for water transport. The purpose of this study was to investigate the
      expression of AQP-1 mRNA and protein in the testis, epididymis, vas deferens,
      ventral prostate, and seminal vesicle from mature mice by using reverse
      transcription polymerase chain reaction (RT-PCR) and Western blotting, and the
      cellular localization of AQP-1 by immunohistochemistry. RT-PCR revealed that AQP
      1 mRNA was expressed in all organs we examined. Western blotting displayed a 29
      kDa band and a 35- to 45-kDa band corresponding to non-glycosylated and/or
      glycosylated AQP-1 in those organs. The immunohistochemical evidence showed that
      AQP-1 was mainly located on the plasma membrane of epithelial cells of the rete
      testis, vas deferens, ventral prostate, seminal vesicle and the non-ciliated
      cells of the proximal and distal efferent ducts. However, AQP-1 was absent from
      spermatogenic cells lining the seminiferous epithelium and from the spermatozoa
      in the lumen of the distal efferent duct. These findings provide valuable
      information on the expression of AQP-1 in male reproductive organs and suggest
      that AQP-1 is involved in water transport to regulate water homeostasis in male
      reproductive physiology.

PMID- 18070240
TI  - Sustained release carriers used to delivery bone morphogenetic proteins in the
      bone healing process.
AB  - Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging
      to the transforming growth factor beta superfamily, especially BMP-2, induce bone
      formation in vivo, and clinical application in repair of bone fractures and
      defects is expected. However, appropriate systems to delivery BMPs for practical
      use need to be developed with the objective to heal cartilage and bone-related
      diseases in medical, dental and veterinary practice. Thus, the aim of this
      article was to present an overview of the principals carriers used to delivery
      BMPs and alternative delivery systems for these proteins.

PMID- 18070241
TI  - Macroscopic and microscopic anatomy of the oviduct in the sexually mature rhea
      (Rhea americana).
AB  - The morphological characteristics of the oviduct of 12 sexually mature rheas
      (Rhea americana) were studied. Only the left oviduct is developed as a long tube
      with a length of 122 +/- 23.1 cm, and is subdivided into infundibulum (15.2 +/-
      4.0 cm), magnum (63.3 +/- 9.4 cm), isthmus (5.6 +/- 3.1 cm), uterus (16.0 +/- 4.2
      cm) and vagina (11.5 +/- 1.4 cm). The mucous membrane of the oviduct, as a whole,
      possesses luminal folds covered by ciliated columnar epithelium with secretory
      cells. The infundibulum part presents a cranial opening with thin and long
      fimbriae with few tubular glands in caudal tubular portion. In the magnum, the
      largest portion of the oviduct, the folds are thicker and are filled with tubular
      glands. The isthmus is short and presents less bulky folds and a few tubular
      glands. A bag-shaped uterus in the cranial area shows thin folds, and in the
      caudal region (shell gland) more ramified folds with few tubular glands. The
      vagina has long luminal folds and a thick muscular tunic; no glands with sperm
      storage characteristics have been observed. In conclusion, the oviduct in
      sexually mature rhea has morphological similarities with the other species of
      birds already described; however it presents its own characteristics to produce a
      big egg.

PMID- 18070242
TI  - A morphological and histological examination of the pan-tropical spotted dolphin
      (Stenella attenuata) and the spinner dolphin (Stenella longirostris) adrenal
      gland.
AB  - The morphology and histology of the cetacean adrenal gland are poorly understood.
      Therefore, this study examined 32 pairs of adrenal glands from 18 pan-tropical
      spotted dolphins (Stenella attenuata) and 14 spinner dolphins (Stenella
      longirostris). In both species, the cortex was pseudolobulated and contained a
      typical mammalian zonation. Medullary protrusions (0-3 per section) and a
      medullary band were identified in both species. For S. attenuata, no statistical
      differences were found in the cortex to medulla (CM) ratio or the percent cross
      sectional area (PCA) of the adrenal glands compared with sex or sexual maturity.
      The mean CM ratio for S. attenuata was 2.34 and the PCA was 64.4% cortex, 29.4%
      medulla and 6.2%'other'. 'Other' indicates blood vessels, connective tissue and
      the gland capsule itself. For S. longirostris, there was no statistical
      difference in the CM ratio compared with sexual maturity. However, a statistical
      difference was found between the CM ratio and sex, suggesting sexual dimorphism
      (female CM ratio = 2.46 and males = 3.21). No statistical differences were found
      in the PCA of S. longirostris adrenal glands by sexual maturity. However, a
      statistical difference was found between the PCA by sex. Female S. longirostris
      adrenal glands consisted of 65.0% cortex, 27.3% medulla and 7.7% 'other', whereas
      male adrenal glands consisted of 71.7% cortex, 22.7% medulla and 5.6% 'other'.

PMID- 18070243
TI  - The effects of ethanol consumption on vasculogenesis potential in nonhuman
      primates.
AB  - BACKGROUND: Vasculogenesis is essential to the preservation and repair of damaged
      or diseased vessels. Alcohol is the most commonly abused drug among young adults,
      but its effects on vessel growth and repair are unknown. The basis of vascular
      repair is endothelial progenitor cell (EPC) recruitment to assist in the
      formation of new vascular network (vasculogenesis). Therefore, the objective of
      this study was to measure the effects of ethanol consumption on the production,
      mobilization and vasculogenesis potential EPCs in nonhuman primates. METHODS:
      Four to five year-old (young adult) male rhesus monkeys consumed monkey chow and
      water (Control, n = 7), or chow and water + ethanol (Alcohol, 2.45 g/d, n = 7)
      for 12 months. Peripheral blood (PB) and bone marrow (BM) samples were collected
      for fluorescence-activated cell-sorting analysis of cell surface antigens (CD45,
      CD31, CD44, CD133, VEGF-R2 - or KDR); and for capillary formation on Matrigel
      coated plates. RESULTS: There were greater numbers of nonhematopoeitic stromal
      cells (CD45-) and putative mesenchymal progenitor cells (CD45-/CD44+) in the PB
      and BM of Alcohol versus Control monkeys (p < 0.05). Additionally, there were
      greater numbers of EPCs (CD45-/CD133+/KDR+) in the BM and PB of Alcohol versus
      Control monkeys (p < 0.05). However, the EPCs of Alcohol monkeys were less likely
      to form capillaries on matrigel-coated plates than Control monkeys (p < 0.05).
      CONCLUSIONS: Ethanol consumption in monkeys markedly increased the production and
      mobilization of EPCs, but decreased their ability to form capillaries. The
      pathophysiologic consequences of such effects are unclear, but may represent an
      ethanol-induced chronic stress on the BM, resulting in EPC.

PMID- 18070244
TI  - Time trends in heavy drinking among middle-aged and older adults in Denmark.
AB  - BACKGROUND: Studies have indicated an increasing proportion of heavy drinking
      among middle-aged and older Danes. Trends in consumption are often extremely
      sensitive to influence from various components of the time trends but only few
      have explored the age, period and cohort-related influences on late life alcohol
      consumption. By using age, period, and cohort modeling this study explores the
      time trends in heavy drinking. METHODS: Data derive from five National Health and
      Morbidity Surveys conducted by the Danish National Institute of Public Health in
      1987, 1994, 2000, 2003, and 2005. A total of 15,144 randomly selected Danes
      between the age of 50 and 74 were interviewed about their alcohol intake on the
      last weekday and their alcohol intake in the last week. By applying the age
      period-cohort model the probability of heavy alcohol drinking is estimated to
      separate the influence of age, period (calendar time) and cohort (year of birth).
      RESULTS: The unadjusted probability of heavy drinking declines by age and
      increases by calendar year and year of birth for both men and women. However, the
      negative effect of age is attenuated for women when adjusted for birth cohort,
      indicating that the proportion of heavy drinking women increases in younger birth
      cohorts. This trend is not observed for men as their drinking pattern mainly
      increase slightly by calendar year. CONCLUSIONS: Our Danish observations for
      older aged individuals correspond to the social and cultural changes in the 1960s
      and 1970s that possibly have affected the drinking behavior of the cohorts. Time
      trend analyses, such as this may serve as an excellent opportunity to extrapolate
      and forecast alcohol mortality and morbidity.

PMID- 18070245
TI  - Naltrexone is associated with reduced drinking by alcohol dependent patients
      receiving antidepressants for mood and anxiety symptoms: results from VA
      Cooperative Study No. 425, "Naltrexone in the treatment of alcoholism".
AB  - BACKGROUND: It is not clear whether naltrexone is effective in reducing alcohol
      consumption among patients with clinically significant mood symptoms and whether
      naltrexone favorably interacts with antidepressant medications when they are co
      prescribed. METHODS: This study reflects a secondary analysis of the first 13
      weeks of VA CSP #425, a study that evaluated the efficacy of naltrexone 50 mg/d
      in 627 alcohol dependent military veterans receiving Twelve Step Facilitation
      therapy at 20 VA Medical Centers. This study included patients with comorbid mood
      and anxiety disorders, providing they did not need treatment for these comorbid
      conditions at the time of study entry. Sixty patients developed sufficiently
      severe mood symptoms while on study medication that they required antidepressant
      treatment. This analysis evaluated whether the efficacy of naltrexone and placebo
      was influenced by the prescription of antidepressant medications to some study
      patients for their mood and anxiety symptoms. RESULTS: In patients randomized to
      placebo (n = 209), prescription of antidepressants was associated with a
      significantly higher percentage of drinking days (lsmean = 24.4, se = 4.85 vs.
      lsmean = 12.9, se = 1.69, p = 0.02). Although the group of patients receiving
      naltrexone (n = 418) was larger than the group assigned to placebo, there were no
      significant differences in drinking-related outcomes in the groups who did or did
      not receive antidepressants (lsmean = 11.5, se = 1.18 vs. lsmean = 12.9, se =
      1.69, p = 0.47). Among the group of patients receiving antidepressants,
      naltrexone prescription was associated with a reduction in the percent drinking
      days compared to placebo [lsmean = 10.1, se = 3.47 vs. lsmean = 24.4, se = 4.85,
      F(1,556) = 5.84, p = 0.02]. CONCLUSIONS: Further investigation will be needed to
      determine whether naltrexone is efficacious among depressed alcohol dependent
      patients and whether naltrexone and antidepressant medications show interactive
      efficacy for treating alcohol dependence.

PMID- 18070247
TI  - Gene therapy reduces ethanol intake in an animal model of alcohol dependence.
AB  - BACKGROUND: Some gene polymorphisms strongly protect against the development of
      alcoholism. A large proportion of East Asians carry a protective inactivating
      mutation in aldehyde dehydrogenase (ALDH2*2). These subjects display high levels
      of blood acetaldehyde when consuming alcohol, a condition that exerts a 66 to 99%
      protection against alcohol abuse and alcoholism. Present knowledge allows the
      incorporation of therapeutic genes that can modify the expression of disease
      predisposing genes, an effect that can last from months to years. In line with
      the above, we have tested if inhibiting the expression of the aldehyde
      dehydrogenase gene (ALDH2) by an anti-Aldh2 antisense gene can curtail the drive
      of alcohol-dependent animals to consume alcohol. METHODS: Wistar-derived rats
      bred as high alcohol drinkers (UChB; Universidad de Chile Bibulous) were rendered
      alcohol dependent by a 2-month period of voluntary ethanol (10%) intake,
      subjected to a 3-day withdrawal period and further allowed access to 10% ethanol
      for only 1 hour each day. This condition results in a high ethanol intake (1.2
      g/kg/60 min) which is 10 times higher than that of naive UChB rats. RESULTS: The
      single intravenous administration of an anti-Aldh2 antisense gene carried by an
      adenoviral vector reduced liver ALDH2 activity by 85% (p < 0.002) and inhibited
      voluntary ethanol intake by 50% (ANOVA p < 0.005) for 34 days. CONCLUSIONS: This
      proof-of-principle study indicates that gene therapy approaches can be employed
      to achieve a long-term reduction of alcohol intake in alcohol-dependent animals
      and suggests that gene vectors may be developed as long-lasting therapeutic
      adjuncts for the treatment of alcoholism.

PMID- 18070246
TI  - Differential modulation of ethanol-induced sedation and hypnosis by metabotropic
      glutamate receptor antagonists in C57BL/6J mice.
AB  - BACKGROUND: Emerging evidence implicates metabotropic glutamate receptor (mGluR)
      function in the neurobiological effects of ethanol. The recent development of
      subtype specific mGluR antagonists has made it possible to examine the roles of
      specific mGluRs in biochemical and behavioral responses to ethanol. The purpose
      of the present study was to determine if mGluRs modulate the acute sedative
      hypnotic properties of ethanol in mice. METHODS: C57BL/6J mice were tested for
      locomotor activity (sedation) and duration of loss of the righting reflex
      (hypnosis) following acute systemic administration of ethanol alone or in
      combination with the mGluR5-selective antagonist, 2-methyl-6
      (phenylethynyl)pyridine (MPEP), the mGluR1-selective antagonist, 7
      (hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt), or the
      mGluR2/3-selective antagonist (2S)-2-Amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3
      (xanth-9-yl) propanoic acid (LY341495)). RESULTS: MPEP (10 and 30 mg/kg)
      significantly enhanced both the sedative and hypnotic effects of ethanol, while
      LY341495 (10 and 30 mg/kg) significantly reduced the sedative-hypnotic effects of
      ethanol. CPCCOEt had no effect at any concentration tested. Further loss of
      righting reflex experiments revealed that LY341495 (30 mg/kg) significantly
      reduced hypnosis induced by the gamma-aminobutyric acid type A (GABAA) positive
      modulators, pentobarbital (50 mg/kg) and midazolam (60 mg/kg), and the N-methyl-d
      aspartate (NMDA) receptor antagonist, ketamine (150 mg/kg), while MPEP (30 mg/kg)
      only significantly enhanced the hypnotic properties of ketamine (150 mg/kg).
      CONCLUSIONS: These findings suggest that specific subtypes of the metabotropic
      glutamate receptor differentially modulate the sedative-hypnotic properties of
      ethanol through separate mechanisms of action, potentially involving GABA(A) and
      NMDA receptors.

PMID- 18070248
TI  - The 3' part of the dopamine transporter gene DAT1/SLC6A3 is associated with
      withdrawal seizures in patients with alcohol dependence.
AB  - BACKGROUND: Some studies have reported that the A9 allele of the variable
      nucleotide tandem repeat (VNTR) of the gene which encodes the dopamine
      transporter (DAT1/SLC6A3) is associated with alcoholism withdrawal symptoms such
      as alcohol withdrawal seizures (WSs), whereas others did not. We investigated
      whether polymorphisms within the DAT1 gene are associated with WS taking into
      account some of the confounding factors such as the severity of alcohol
      dependence. METHODS: To further assess the role of this gene in WS, we genotyped
      the VNTR and 7 single nucleotide polymorphisms (SNPs) encompassing the DAT1 gene
      in a sample of 250 alcohol-dependent subjects (175 men and 75 women), of whom 24%
      exhibited WSs, taking into account the severity of alcohol dependence. RESULTS:
      The VNTR is associated with an increased risk of WSs (odd ratio = 3.5; p =
      0.019), even when controlling for confounding factors (p = 0.031). As 2 SNPs, in
      roughly the same location of the gene (namely rs27072 and rs27048), are also
      associated with WSs, it is possible that the initial association of the VNTR
      polymorphism was tagging a specific haplotype of this gene. Indeed, in our sample
      of alcohol-dependent patients, 2 haplotypes were associated with a significantly
      different risk of WSs. CONCLUSIONS: The present study adds evidence for a
      significant role of the 3' part of the DAT1 gene in WS of alcohol-dependent
      patients, not only because it is in accordance with previous work, but also
      because of larger statistical power (as relying on a sample over sampled with the
      studied phenotype), as it gives a more precise analysis of different SNPs within
      the DAT1 gene, and as it confirms the association when major potentially
      confounding factors are taken into account in a logistical regression analysis.

PMID- 18070249
TI  - Children's introduction to alcohol use: sips and tastes.
AB  - BACKGROUND: Sipping or tasting alcohol is one of the earliest alcohol use
      behaviors in which young children engage, yet there is relatively little research
      on this behavior. The present research describes the prevalence of sipping or
      tasting in a community sample of children, examines the sociodemographic
      correlates and social contexts of this behavior, and tests whether variables
      reflecting psychosocial problem-behavior proneness, that predict adolescent
      drinking, account for this behavior. METHODS: A sample of 452 children (238
      girls) aged 8 or 10 and their families was drawn from Allegheny County PA using
      targeted-age directory sampling and random digit dialing procedures. Children
      were interviewed using computer-assisted interviews. Logistic regression analyses
      were used to examine the univariate and multivariate correlates of
      sipping/tasting. RESULTS: Thirty-nine percent of the sample had only sipped or
      tasted alcohol (35% of 8 year olds and 48% of 10 year olds), while 6% reported
      having had a drink of alcohol (5% and 7%, respectively). African-American
      children were less likely than White children to be sippers. Neither gender nor
      mother's education related to sipping status. Most sipping was done in a family
      context. Sipping/tasting did not generally relate to variables reflecting
      psychosocial proneness for problem behavior. Instead, the variables most
      predictive of sipping/tasting were perceived parents' drinking status, perceived
      parents' approval for child sipping, mother's drinking frequency, and children's
      attitudes toward sipping/tasting alcohol. CONCLUSIONS: Young children's
      sipping/tasting of alcohol reflects parental modeling of alcohol use and
      increased opportunities to try alcohol in the home rather than deliberate family
      socialization of alcohol use, and appears not to be a precocious manifestation of
      a psychosocial proneness to engage in problem behavior.

PMID- 18070251
TI  - GABAA alpha 4 receptor subunits and ethanol: a knockout punch?

PMID- 18070250
TI  - Functional consequences of GABAA receptor alpha 4 subunit deletion on synaptic
      and extrasynaptic currents in mouse dentate granule cells.
AB  - BACKGROUND: The alpha 4 subunit-containing gamma-aminobutyric acid (A) receptors
      (GABA(A)Rs) are highly expressed primarily at extrasynaptic sites in the dentate
      gyrus (DG) and thalamus and are suspected to contribute to tonic inhibition that
      is sensitive to potentiation by gaboxadol and ethanol (EtOH). Global alpha 4
      subunit knockout (KO) mice exhibit greatly reduced tonic currents and
      insensitivity to ataxic, sedative and analgesic effects of gaboxadol compared to
      wild type (WT) controls. The alpha 4 KO mice were also significantly more
      sensitive to pentylenetetrazol-induced seizures. However, no differences were
      observed between alpha 4 KO and WT mice in other baseline behaviors or in the
      effects of EtOH on these behaviors. To examine possible functional and
      pharmacological GABA(A)R alterations, and search for causes for the lack of
      differences in EtOH behaviors we studied the effects of acute EtOH application on
      GABA(A)R-currents of DG cells from alpha 4 KO and WT control mice complemented by
      Western blot measurements. METHODS: We studied the consequences of alpha 4
      subunit deletion using Western immunoblotting and whole cell patch recordings
      from DG cells in brain slices from alpha 4 KO and WT mice. RESULTS: The magnitude
      of tonic current and its potentiation by EtOH (10 to 100 mM), alphaxalone (3
      microM), and Ro15-4513 (0.3 microM) was greatly attenuated in alpha 4 KO mice.
      The kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in alpha 4 KO
      mice were significantly slower compared to WT mice. Potentiation of mIPSCs by
      alphaxalone was greatly reduced in alpha 4 KO mice. Ro15-4513 had no effect on
      mIPSCs from WT or KO mice. However, mIPSCs of alpha 4 KO mice were significantly
      more sensitive to EtOH than those from WT mice. The gamma 2 subunit protein
      levels were selectively increased in hippocampus and thalamus, but not cortex of
      alpha 4 KO mice. CONCLUSIONS: These data suggest that the global loss of alpha 4
      subunits leads to region- and cell location-specific compensatory increases in
      gamma 2 subunits, which in turn alter the pharmacological sensitivity of synaptic
      and extrasynaptic GABA(A)R-currents. Our data also suggests that while
      enhancement of tonic inhibitory currents by gaboxadol, alphaxalone, and EtOH are
      reduced, and behavioral sensitivity to gaboxadol and alphaxalone may be reduced,
      compensatory changes in synaptic GABA(A)R subunits may prevent similar reductions
      in behavioral sensitivity to EtOH.

PMID- 18070252
TI  - Metabotropic actions of kainate receptors in the CNS.
AB  - Kainate receptors (KARs), together with NMDA and alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate receptors (AMPA), are typically described as
      ionotropic glutamate receptors. Although ionotropic functions for KARs are
      beginning to be characterized in multiple brain regions, both, in the pre- and
      post-synaptic compartments of the synapse, there is accumulating evidence that
      KARs mediate some of their effects without invoking ion-fluxes. Thus, since 1998,
      when the first metabotropic action of KARs was described in the modulation of
      GABA release in hippocampal interneurons, there have been increasing reports that
      some of the functions of KARs involve the participation of intracellular
      signalling cascades and depend on G protein activation. These surprising
      observations, attesting metabotropic actions of KARs, akin to those usually
      attributed to seven transmembrane region G protein-coupled receptors, make the
      physiological classification and description of glutamate receptors more complex.
      In the present review, we describe the metabotropic roles of KARs in the CNS and
      discuss the intriguing properties of this receptor which, structurally shows all
      the facets of a typical ionotropic receptor, but appears to express a
      metabotropic remit at some key synapses.

PMID- 18070253
TI  - Assessing the quality of colorectal cancer care: do we have appropriate quality
      measures? (A systematic review of literature).
AB  - RATIONALE, AIMS AND OBJECTIVES: The burden of illness from colorectal cancer
      (CRC) can be reduced by improving the quality of care. Identifying appropriate
      quality measures is the first step in this direction. We identified process
      measures currently available to assess the quality of diagnosis and management of
      CRC. We also evaluated the extent to which these measures are ready to be
      implemented in clinical practice, and identified areas for future research.
      METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, and
      relevant grey literature. We identified 3771 abstracts and reviewed 74 articles
      that included quality measures for diagnosis or management of CRC. Measures from
      traditional quality improvement literature, and from epidemiological and other
      studies that included quality measures as part of their research agenda, were
      considered. In addition, we devised a summary rating scale (IST) to appraise the
      extent of a measure's importance and usability, scientific acceptability and
      extent of testing. RESULTS: The coverage of general process measures in CRC is
      extensive. Most measures are important, but need to be developed and field
      tested. The best available measures relate to pathology and chemotherapy. No
      measures are available for assessing quality of management of stage IV rectal
      cancer and hepatic metastasis; chemotherapy for stage II colon cancer; and
      procedure notes. CONCLUSIONS: There is an urgent need to refine existing measures
      and to develop scientifically accurate quality measures for a comprehensive
      assessment of the quality of CRC care. The role of the federal government and
      professional societies is critical in pursuing this goal.

PMID- 18070254
TI  - Asthma patients with low perceived burden of illness: a challenge for guideline
      adherence.
AB  - RATIONALE AND AIMS: The reason why many patients seem to tolerate suffering from
      sub-optimal treated asthma remains unclear. The aim was to evaluate the guideline
      adherence combined with quality of life of patients with moderate to severe
      asthma. METHODS: 256 asthma patients from 43 primary care practices in Saxony
      Anhalt filled in a questionnaire including the Asthma Quality of Life
      Questionnaire (AQLQ), the Patient Health Questionnaire (PHQ-D) and questions
      evaluating the asthma severity, medication and self-management. RESULTS: 43.4%
      suffered from moderate to severe asthma. Drug treatment accorded with guidelines
      in 36.9%, drug dosage of inhaled steroids was too low in 34.3%, and 21.5% were
      not treated according to guidelines. A total of 7.3% of the patients received end
      of-dose therapy. AQLQ declined and depression rose with asthma severity and
      guideline non-adherence (P < 0.001). Only 29.1% received asthma education.
      However, 64.5% of the patients without education did not want to receive
      education. They had a higher quality of life, lower depression (P < 0.001) and
      lower use of steroids (P = 0.016). Higher depression scores where related with
      hospital admission (OR 3.29; 95% CI 1.57-6.87 for each quartile of PHQ-D) and
      unscheduled home visits or ambulatory care (OR 1.58; 1.07-2.33). CONCLUSION:
      There is a large variation of asthma severity which can partly be explained by
      the guideline adherence of medication and deficits of patients' management. The
      perceived burden of illness plays a more important role for education and self
      management than the real severity of disease. Therefore, target-oriented
      interventions are needed to identify and motivate patients at risk.

PMID- 18070255
TI  - Effectiveness of a lifestyle modification programme in weight maintenance in
      obese subjects after cessation of treatment with Orlistat.
AB  - OBJECTIVE: To examine the efficacy of a lifestyle modification programme in
      weight maintenance for obese subjects after cessation of treatment with Orlistat.
      METHODS: Fifty-five subjects with and without diabetes mellitus were randomized
      to a lifestyle modification programme or to usual care at the end of 6 months'
      treatment with Orlistat. The intervention programme was nutritionist led,
      consisting of components of dietary management, physical activity, peer group
      support and discussion using techniques of self-monitoring, stimulus control and
      cognitive restructuring. Anthropometric indices, body composition, basal
      metabolic rate, blood pressure, fasting glucose, glycosylated haemoglobin, lipid
      profile, 24-hour urinary albumin excretion, dietary intake, physical activity
      level, and quality of life were assessed before and after the intervention
      period. Results Subjects in the intervention group maintained their weight loss
      and favourable anthropometric, metabolic, dietary intake, physical activity and
      quality of life profiles, while most parameters deteriorated in the usual care
      group, being more marked in subjects with diabetes. The magnitude of weight gain
      was comparable to that lost during Orlistat treatment. CONCLUSION: A specially
      designed nutritionist-led lifestyle modification programme for obese subjects is
      effective in weight maintenance after treatment with Orlistat, in the absence of
      which the benefits of drug treatment were lost. The magnitude of the effect of
      lifestyle modification is comparable to that observed with Orlistat.

PMID- 18070256
TI  - Effects of a nationwide programme: interventions to reduce perceived barriers to
      collaboration and to increase structural one-on-one contact.
AB  - OBJECTIVE: To describe the implementation of a nationwide programme and to
      determine the effects of specific quality improvement (QI) interventions within
      this programme on perceived barriers to collaboration between general
      practitioner (GPs) and mental health professionals and frequency of structural
      one-on-one contact regarding individual patients. METHODS: The implementation of
      regional QI-interventions, perceived barriers to collaboration, and frequency of
      structural one-on-one contact, were assessed in a cohort study involving two
      surveys (2001 and 2003) among a random sample of 2757 GPs. RESULTS: 1336 and 1358
      GPs returned baseline and follow-up questionnaires respectively. Most of the
      interventions were only offered to a minority of GPs. Less than 25% of GPs that
      had been offered interventions actually participated. The frequency of structural
      one-on-one contact with mental health professionals did not change, but barriers
      to collaboration decreased between 2001 and 2003. For GPs who actually
      participated in interactive small group meetings or in intervention in which
      mental health professionals were integrated in general practice, a reduction of
      perceived barriers could be observed as well as an increase in the frequency of
      structural one-on-one contact. CONCLUSION: Interventions that could be
      characterized as interactive small group meetings as well as interventions that
      involved the integration of mental health professionals in general practice led
      to a reduction of perceived barriers as well as an increase in the frequency of
      structural one-on-one contact. These findings add to the knowledge of which
      interventions have an effect on the collaboration between different health care
      providers.

PMID- 18070257
TI  - Estimation and prediction system for multi-state disease process: application to
      analysis of organized screening regime.
AB  - RATIONALE, AIMS AND OBJECTIVES: The disease progression of cancer and non
      malignant chronic disease often involve a multi-state transition. However,
      estimation of parameters and prediction regarding the multi-state disease process
      are complex. This study aimed to develop an estimation and prediction system with
      a computer-assisted software using SAS/SCL as a platform to predict the risk of
      any outcome arising from the underlying multi-state process with or without the
      incorporation of individual characteristics. METHOD: The computer-aided system is
      first constructed following the theoretical framework of stochastic process. The
      functions provided in this software include model specification, formulation of
      likelihood function, parameter estimation, model validation and model prediction.
      An example of breast cancer screening for a high-risk group in Taiwan was used to
      demonstrate the usefulness of this software. RESULTS: The natural history of
      breast cancer of a three-state disease process has been demonstrated. Two
      suspected risk factors, late age at first full-term pregnancy and obesity, were
      considered by the form of the proportional hazard model. Formulation of intensity
      matrix, likelihood function, assignment of initial values, and parameter
      constraint and estimation were successfully demonstrated in model specification.
      Model validation suggested a good fit of the constructed model. The application
      of model prediction enables one to project the effectiveness of organized
      screening by different inter-screening intervals from a policy level or from an
      individual basis. CONCLUSIONS: A computer-aided estimation and prediction system
      for multi-state disease process was developed and demonstrated. This system can
      be applied to data with the property of multi-state transitions in association
      with events or disease.

PMID- 18070258
TI  - Overall self-rated health as an outcome indicator in primary care.
AB  - RATIONALE, AIMS AND OBJECTIVES: The ultimate goal of health care systems is to
      improve overall health from the patient's point of view. However, overall self
      rated health is not routinely monitored as a performance indicator. The purpose
      of this study was to investigate the feasibility of using a measure normally
      employed in community health surveys as a quality indicator in primary care
      clinics. METHODS: In order to do so, we conducted a cross-sectional survey of
      community medicine patients treated in five clinics in Amarillo, Texas to test
      the theory that, in primary care patients, a single-item measure of self-rated
      health is significantly related to the usual risk factors found in community
      health surveys (environmental factors, demographic characteristics and health
      behaviours). RESULTS: Multiple logistic regression analysis revealed that age,
      race, frequent mental distress, current smoking and health confidence were
      independently related to the odds of reporting good health. CONCLUSION: Our
      results support using a single-item measure of self-rated health in primary care.
      Our data also suggest that encouragement of health confidence would appear to be
      in the best interests of patients.

PMID- 18070259
TI  - Examining the hierarchical factor structure of the SF-36 Taiwan version by
      exploratory and confirmatory factor analysis.
AB  - RATIONALE: The purpose of this study was to examine the factor structure of the
      Medical Outcome Study Short Form-36 Taiwan version (SF-36 Taiwan version) using
      data from the 2001 National Health Interview Survey in Taiwan. METHOD: The 2001
      National Health Interview Survey was conducted by stratified multistage
      systematic sampling, resulting in 19,777 valid responses for the SF-36 Taiwan
      version. In this study, the 19,777 participants were randomly divided into two
      independent samples. One sample (n = 9856) was used for exploratory factor
      analysis (EFA), and the other (n = 9921) was used for confirmatory factor
      analysis (CFA). RESULTS: The EFA suggested a seven-first-order-factor structure
      for the SF-36 Taiwan version. In addition, hierarchical EFA revealed that there
      was only one second-order factor underlying the seven first-order factors.
      Further, CFA was conducted on the other sample to compare the performances of the
      original model with eight first-order factors and two second-order factors, and
      the revised model with seven first-order factors and one second-order factor. The
      CFA results revealed that the original model was better than the revised model.
      CONCLUSION: According to the EFA and CFA, it can be concluded that the original
      structure is still acceptable for the SF-36 Taiwan version.

PMID- 18070260
TI  - The relationship between second-year medical students' OSCE scores and USMLE Step
      2 scores.
AB  - RATIONALE, AIMS AND OBJECTIVES: A valid tool to measure clinical competency early
      in medical school could identify students who may require special educational
      attention. The overall aim is to assess the relationship between students' scores
      on an objective structured clinical examination (OSCE) given in the second year
      of medical school and their subsequent performance on Step 2 of the United States
      Medical Licensing Examination (USMLE Step 2). METHODS: Participants were 390
      second-year medical students participating in a required OSCE; complete data
      (Medical College Admission Test, OSCE, USMLE Step 1 and Step 2 scores) were
      available for 340 students (87%). Univariate correlations and linear regression
      analyses were performed. RESULTS: Total OSCE score was moderately correlated with
      USMLE Step 2 score (r = 0.395, P < 0.001), as were two skills subscores of the
      OSCE, differential diagnosis (r = 0.343, P < 0.001) and identification of
      abnormality (r = 0.322, P < 0.001). In linear regression analysis, neither OSCE
      total score nor any of the subscores independently predicted Step 2 scores; only
      Step 1 score (beta = 0.687, P < 0.001) and female sex (beta = 0.152, P < 0.001)
      remained independent correlates of Step 2 score. CONCLUSION: OSCEs early in
      medical school can be useful in the early assessment of clinical competence.

PMID- 18070261
TI  - A model to analyse costs and benefit of intensified diabetic foot care in
      Austria.
AB  - RATIONALE, AIMS AND OBJECTIVES: The diabetic foot is a common late complication
      among diabetic patients and due to its consequences an important financial burden
      for society. Intensified treatment has proved to reduce amputation rates, but in
      Austria so far no data have been available about financial implications and long
      term effects of intensified treatment. The objective was to retrieve cost data
      for intensified treatment of diabetic foot ulcers and to estimate the long-term
      outcome. METHODS: A retrospective data analysis of 119 ulcers was done to get
      outcomes and costs for intensified treatment in a specialized outpatient hospital
      department in an Austrian setting. One-year results were categorized according to
      the San Antonio wound classification. Using a Markov model upon these data, long
      term outcomes and costs for intensified treatment and for standard care were
      calculated. RESULTS: Costs for intensified treatment until healing vary from euro
      1071 (range: 99-4089) per case to euro 7844 (range: 104-25 615) depending on the
      lesion's grade. One-year healing rates are 85.2% for grade A and 71.7%, 84.6% and
      33.3% for the grades B, C and D respectively. The model-based comparison for
      treatment costs shows a cost reduction of 29.8% per patient year in grade A
      ulcerations and 49.7% in grade D for intensified versus standard treatment due to
      lower amputation rates. CONCLUSIONS: These results are the first cost data for
      diabetic foot care in Austria and demonstrate the advantages of intensified care
      over standard care in terms of patient-oriented outcome and financial impact
      pleading for the implementation of specialized foot care facilities and referral
      guidelines to standardize and improve treatment.

PMID- 18070262
TI  - Patient factors associated with attrition from a self-management education
      programme.
AB  - OBJECTIVE: To examine utilization patterns of diabetes self-management training
      (DSME) and identify patient factors associated with attrition from these services
      at an ambulatory diabetes education centre (DEC). METHODS: A retrospective
      medical chart review of first time visits (536) to the centre between 1 August
      2000 and 31 July 2001 was conducted for patients with type 2 diabetes.
      Descriptive analyses were conducted to examine utilization patterns over a 1-year
      period. Multivariable logistic regression was used to identify patient factors
      associated with attrition from DSME and non-use of group education among new
      patients. RESULTS: Almost 50% of new patients withdrew prematurely from
      recommended DSME services over the 1-year period, and only 24.8% attended group
      education. Patient variables such as being older than 65 years of age, primarily
      speaking English, or working full or part-time were associated with attrition
      from DSME and non-use of group education when compared with middle aged, non
      English-speaking, and non-working patients. CONCLUSIONS: High DSME attrition
      rates indicate that retention needs to become a focus of programme policy,
      planning and evaluation to improve programme effectiveness. DSME tailored to the
      cultural and linguistic characteristics of the community, and convenient and
      accessible to working and older patients will potentially increase retention in
      and accessibility to these services.

PMID- 18070263
TI  - Are the outcomes of clinical pathways evidence-based? A critical appraisal of
      clinical pathway evaluation research.
AB  - AIM AND OBJECTIVE: To evaluate the validity of study outcomes of published papers
      that report the effects of clinical pathways (CP). METHOD: Systematic review
      based on two search strategies, including searching Medline, CINAHL, Embase,
      Psychinfo and Picarta from 1995 till 2005 and ISI Web of Knowledge SM. We
      included randomized controlled or quasi-experimental studies evaluating the
      efficacy of clinical pathway application. Assessment of the methodological
      quality of the studies included randomization, power analysis, selection bias,
      validity of outcome indicators, appropriateness of statistical tests, direct
      (matching) and indirect (statistical) control for confounders. Outcomes included
      length of stay, costs, readmission rate and complications. Two reviewers
      independently assessed the methodological quality of the selected papers and
      recorded the findings with an evaluation tool developed from a set of items for
      quality assessment derived from the Cochrane Library and other publications.
      RESULTS: The study sample comprised of 115 publications. A total of 91.3% of the
      studies comprised of retrospective studies and 8.7% were randomized controlled
      studies. Using a quality-scoring assessment tool, 33% of the papers were
      classified as of good quality, whereas 67% were classified as of low quality. Of
      the studies, 10.4% controlled for confounding by matching and 59.1% adopted
      parametric statistical tests without testing variables on normal distribution.
      Differences in outcomes were not always statistically tested. CONCLUSION: Readers
      should be cautious when interpreting the results of clinical pathway evaluation
      studies because of the confounding factors and sources of contamination affecting
      the evidence-based validity of the outcomes.

PMID- 18070264
TI  - Improving the organization of consultation departments in university hospitals.
AB  - RATIONALE: Changes in the demography of doctors require changes in care
      practices. OBJECTIVES: The aim of this study was to identify factors associated
      with doctors' workload in the ophthalmology consultation department of a
      university hospital, with a view to developing methods to improve the
      organization of hospital outpatient clinics. METHODS: A 10-day cross-sectional
      survey was carried out in an ophthalmology outpatient clinic (in- and outpatient
      consultations, including emergencies) specializing in the uveitis care.
      Demographic and management data for each patient were collected on a structured
      form. The doctor's workload was assessed, using a scale taking into account the
      duration of the consultation and the number of diagnostic tests performed, as a
      function of management complexity. RESULTS: Of the 861 consultations studied,
      39.7% were highly complex. The level of complexity of consultations was
      correlated with the type of referral (phi = 0.602), consultation duration (phi =
      0.545), the number of consultations in the previous year (phi = 0.499), and the
      number of diagnostic tests performed (phi = 0.445). Consultations were longer and
      diagnostic tests were more frequently performed if patients had been referred by
      an ophthalmologist, consulted a faculty doctor or a fellow, or presented with
      uveitis. Consultations were also more complex for patients with at least four
      previous consultations in the past year. CONCLUSIONS: Type of referral, status of
      the attending doctor and number of consultations within the course of 1 year were
      associated with doctors' workload and could be taken into account to predict the
      duration of complexity of consultations when scheduling appointments.

PMID- 18070265
TI  - Evaluating complex public health interventions: theory, methods and scope of
      realist enquiry.
AB  - The standard models used in the study of complex public health interventions are
      inadequate. They adopt a simple empiricist theoretical foundation and attempt to
      graft onto an essentially open social system a contrived laboratory
      experimentation typically in the form of a randomized, controlled trial. By
      understanding the ontological and epistemological claims of critical realism, it
      is possible to transcend the methodological inadequacy of the standard model
      approach. Critical realism posits a substantive causal theory, an end to fact
      value dualism, and a coherent and emancipatory model of social action; all of
      these features amount to a systematic and compelling account of public health
      practice and a coherent approach to evaluation of complex public health
      interventions.

PMID- 18070266
TI  - Validation of the German Glasgow children's benefit inventory.
AB  - OBJECTIVE: The aim of this study was to validate the German Glasgow Children's
      Benefit Inventory (GCBI) in children with different surgical interventions.
      MATERIAL AND METHODS: The GCBI was translated by using accepted forward-backward
      translation techniques and mailed to 741 parents whose children underwent either
      an otorhinolaryngological (n = 641) or an urological intervention (n = 100). The
      assessment was performed in a retrospective manner at the Medical University
      Innsbruck, Austria between January and March 2006. An exploratory principal
      component factor analysis with varimax rotation using factor loadings of >or=0.40
      to allocate items to a scale was performed. Frequencies, means and standard
      deviations were used to describe patient, clinical, sociodemographic, and scale
      characteristics. RESULTS: The questionnaire was completed and returned by 325
      patients (43.9%). The GCBI showed a high internal consistency (alpha = 0.84). The
      four-factor solution, emotional, vitality, learning and physical health explained
      55.7% of variance. CONCLUSION: The German version of the GCBI was proven to be
      valid and reliable. It is suitable for subjective outcome analysis of different
      paediatric interventions from infants to adolescents.

PMID- 18070268
TI  - Simple sample size calculation.

PMID- 18070267
TI  - The case-mix of chronic illness hospitalization rates in a managed care
      population: implications for health management programmes.
AB  - OBJECTIVE: This paper reports on the case-mix of hospitalized patients based on
      their health plan enrollment and utilization experience, absent a health
      management (HM) programme. The implications for achieving targeted reductions in
      admissions within the context of implementing a population hm programme are
      discussed. STUDY DESIGN: descriptive. METHODS: Members were identified with
      asthma, coronary artery disease, congestive heart failure and diabetes. These
      cohorts were then mapped to disease-specific hospitalizations across a 2-year
      period (2004-2005). Four distinct case-mix categories were developed. Group 1
      comprised members hospitalized for the specific condition in both years. Group 2
      comprised all identified members of a disease cohort in 2004 that were not
      hospitalized in that year but were admitted for the condition in 2005. Members
      were assigned to Group 3 if they were hospitalized in 2005, did not appear in the
      2004 identified cohort but were, in fact, enrolled in the health plan. Group 4
      comprised new health plan enrollees in 2005 and were subsequently hospitalized
      during that year. RESULTS: Of the total admissions in 2005, on average 6.4% came
      from Group 1, 62.4% came from group 2, 10% from group 3 and 21.2% from Group 4.
      CONCLUSIONS: If an HM programme was to be implemented in this population, the
      typical identification methods currently used by the industry would have resulted
      in most hospitalized patients either being initially classified as low risk or
      going undetected. Improving identification and stratification methods will allow
      HM programmes to better tailor interventions to impact hospitalization rates for
      the chronically ill.

PMID- 18070269
TI  - Doctors' obstetric experience and Caesarean section (CS): does increasing
      delivery volume result in lower CS likelihood?

PMID- 18070270
TI  - Ensuring quality in platelet immunology.

PMID- 18070271
TI  - A modified rapid monoclonal antibody-specific immobilization of platelet antigen
      assay for the detection of human platelet antigen (HPA) antibodies: a multicentre
      evaluation.
AB  - BACKGROUND: The monoclonal antibody-specific immobilization of platelet antigens
      (MAIPA) assay is the cornerstone technique for the detection and identification
      of human platelet antigen (HPA) antibodies. However, the original technique
      described by Kiefel and colleagues requires approximately 8 h adding to
      diagnostic delay. Moreover, proficiency exercises indicate that there are
      substantial variations in the MAIPA protocol, and that these may account for
      interlaboratory differences in sensitivity and specificity. STUDY DESIGN AND
      METHODS: A review of current MAIPA assay protocols from six laboratories together
      with performance in quality-assessment schemes identified several key variables
      potentially affecting the assay results. An optimized protocol was derived and
      assay time reduced to 5 h. The modified rapid MAIPA (MR-MAIPA) assay was
      evaluated using 61 samples with a range of HPA antibodies typically encountered
      in cases of fetomaternal alloimmune thrombocytopenia (n = 22), post-transfusion
      purpura (n = 8), platelet refractoriness (n = 7) and other platelet immune
      conditions (n = 24). The sensitivity of the assay was assessed using three
      international standards and the recombinant HPA-1a antibody CamTran007. The
      results obtained were compared with the original findings obtained with the local
      MAIPA assays. In addition, four different glycoprotein IIb/IIIa capture
      monoclonal antibodies were evaluated for their effect on assay sensitivity.
      RESULTS: Complete concordance was found between the original MAIPA results and
      those obtained with the new assay when testing a selected panel of clinical
      samples. The modified assay had nanogram level sensitivity for the detection of
      HPA-1a antibodies and titration of HPA-1a and HPA-5b antibody sensitivity
      standards yielded end-points equal to or greater than the mean recorded in
      international workshops. CONCLUSION: The MR-MAIPA assay offers improved
      turnaround for the detection of HPA antibodies without loss of sensitivity.

PMID- 18070272
TI  - Monoclonal platelet antigen capture assays (MAIPA) and reagents: a statement.
AB  - This statement concerning the monoclonal-specific immobilization of platelet
      antigens (MAIPA) has been written on behalf of the International Society of Blood
      Transfusion--Working Party on Platelet Immunology. The MAIPA technique is
      considered as the gold standard reference technique in platelet immunology. The
      assay performed with reagents labelled for 'research only' is acceptable as long
      as it is regularly evaluated by participation of laboratories in national or
      international workshops held with reference laboratories.

PMID- 18070273
TI  - Report on the 13th International Society of Blood Transfusion Platelet Immunology
      Workshop.
AB  - BACKGROUND AND OBJECTIVES: The aim of the 13th International Society of Blood
      Transfusion Platelet Immunology Workshop was to compare the sensitivity and
      specificity of the in-house method for the detection of human platelet antigen
      (HPA) antibodies currently used in participating laboratories with a modified
      rapid protocol for the monoclonal antibody (mAb) immobilization of platelet
      antigen (MR-MAIPA) assay. MATERIALS AND METHODS: Twenty-eight laboratories from
      15 countries participated. A set of four freeze-dried minimum potency reference
      reagents with known single-specificity HPA antibodies were supplied for testing
      by titration with both assays and two coded freeze-dried plasma samples were
      provided for antibody specificity testing. Critical reagents and materials for
      the MR-MAIPA were provided including lyophilized panel platelets and five capture
      mAbs. RESULTS: Titration of the reference standards showed that the sensitivity
      of the MR-MAIPA was the same as the in-house methods. The proposed replacement
      anti-HPA-1a reference reagent 05/106 gave results that did not differ
      significantly from the current reference reagent 93/710. The results with the two
      blinded samples showed that in the first sample, 27 out of the 28 laboratories
      were able to correctly identify the anti-HPA-1a present when using their
      respective in-house methods, but only 23 correctly identified the antibody when
      using the rapid MAIPA method. The results from the second sample, which contained
      multispecificities, showed that only 50% of the participants correctly identified
      all five antibodies present using their in-house method. The results for the
      rapid MAIPA were lower, with only 32% identifying all specificities. The
      variability in the reconstitution of the freeze-dried platelets may have been one
      of the contributing factors to the poorer results. CONCLUSIONS: The sensitivity
      of the MR-MAIPA compared favourably with that of the in-house methods. Most
      laboratories were able to identify anti-HPA-1a alone in Sample 1 but more than
      half of the participants were not able to correctly assign the specificity of all
      HPA antibodies present in the second sample. The usefulness of the panel of
      freeze-dried platelets varied considerably between laboratories.

PMID- 18070274
TI  - The importance of using multiple techniques for detection of platelet antibodies.
AB  - In red cell immunology, it has long been known that no one technique will detect
      all clinically significant antibodies. The same appears to be true for platelet
      immunology, and we highlight this fact by showing four examples of anti-human
      platelet antigen-1a that were not detected by the monoclonal antibody-specific
      immobilization of platelet antigen test, the most commonly used technique. Each
      antibody was found in a case of fetomaternal alloimmune thrombocytopenia in which
      the fetus or neonate was severely affected.

PMID- 18070275
TI  - Collaborative studies to establish the first World Health Organization
      International Standard for detection of human antibody against human platelet
      antigen-3a.
AB  - BACKGROUND AND OBJECTIVES: The platelet-specific antibody anti-human platelet
      antigen-3a (anti-HPA-3a) is involved in neonatal alloimmune thrombocytopenia,
      post-transfusion purpura, and platelet refractoriness. However, HPA-3a antibodies
      are often difficult to detect, probably because the antigen is labile. This
      report describes the production of a freeze-dried preparation of pooled human
      plasma, coded 03/190, containing IgG antibodies against the HPA-3a. The material
      is intended for use as a minimum sensitivity reagent in glycoprotein-specific
      assays currently used for anti-HPA-3a detection. Laboratories can use it to
      assess the sensitivity of their 'in-house' assays for anti-HPA-3a and to
      calibrate local controls for routine use in each batch of tests. MATERIALS AND
      METHODS: Plasma containing anti-HPA-3a was obtained from a mother of two babies
      both born with severe thrombocytopenia, and following dilution it was freeze
      dried in glass ampoules. RESULTS: Two collaborative studies demonstrated that the
      candidate material contained anti-HPA-3a and human leucocyte antigen (HLA) class
      I antibodies, but no other HPA antibodies that might confuse the detection of the
      anti-HPA-3a. The minimum dilution that should give a positive result was
      determined to be 1 : 8 by two further international collaborative studies
      involving a total of 49 laboratories in 23 countries. CONCLUSION: The material
      also contains HLA antibodies and is suitable for use only in techniques that are
      glycoprotein specific (i.e. monoclonal antibody immobilization of platelet
      antigens and enzyme-linked immunosorbent assay) where only HPA antibodies will be
      detected. This standard will allow laboratories to measure their sensitivity of
      detection of anti-HPA-3a and will also allow those laboratories with relatively
      insensitive techniques to monitor their performance as they improve their
      methodology.

PMID- 18070276
TI  - Interlaboratory variation in the detection of HPA-specific alloantibodies and in
      molecular HPA typing.
AB  - BACKGROUND AND OBJECTIVES: Platelet immunology quality assurance exercises have
      been organized by National Institute for Biological Standards and Control since
      1991 and, as of 2006, 35 laboratories participate in the serology section.
      Molecular human platelet antigen (HPA) typing has been included in the exercises
      since 1998 and, as of 2006, 29 laboratories participate in this part of the
      exercise. This report details the performance of laboratories in these two areas.
      MATERIALS AND METHODS: Every 6 months laboratories are sent up to four coded
      serum/plasma samples for testing in their in-house assays for HPA antibody
      detection/identification and four coded whole blood samples to be typed for HPA
      1, -2, -3 -5 and (since 2003) -15 by their molecular typing assays
      ('genotyping'). RESULTS: Fifty-two sera containing HPA-specific alloantibodies
      and 13 sera that were inert, contained only human leucocyte antigen (HLA) class I
      or high-titre anti-A+B antibodies were distributed; 15 sera were issued in more
      than one exercise. The percentage of participating laboratories that were able to
      detect HPA-specific alloantibodies ranged from 15.0 to 100%; the percentage that
      were able to correctly determine the specificities also ranged from 15.0 to 100%.
      Over the 20 serology exercises the percentage of laboratories classified as poor
      performers ranged from 3.1 to 36.7%. A total of 12 780 individual HPA genotyping
      results were assessed. The overall error rate was 0.7% but there was considerable
      variation between HPA alleles. Over 11 exercises the percentage of laboratories
      classified as poor performers varied from 6.3 to 26.3%. CONCLUSIONS: The ability
      to detect and to identify platelet-specific alloantibodies varied widely between
      laboratories and between various examples of antibodies issued. An increase in
      the number of laboratories screening for HPA-15 antibodies was seen, although
      detection and identification of these antibodies was problematic. The majority of
      examples of HPA-3a antibodies and some examples of HPA-1a and -5b were also
      difficult to detect and identify. In addition, this scheme has shown that despite
      the apparent reliability of molecular typing techniques, mistakes do occur,
      particularly with certain systems. Approximately one in five laboratories
      participating in the serology exercises and one in seven participating in the
      genotyping exercises were classified as poor performer at one point or more
      during the series of exercises.

PMID- 18070277
TI  - Severe fetomaternal alloimmune thrombocytopenia due to anti-human platelet
      antigen (HPA)-1a in a mother with a rare and silenced ITGB3*0101 (GPIIIa) allele.
AB  - BACKGROUND AND OBJECTIVES: Fetomaternal alloimmune thrombocytopenia (FMAIT) is
      caused by maternal antibodies against a human platelet antigen (HPA) present on
      fetal, but absent from maternal platelets. We identified and characterized a case
      of FMAIT due to anti-HPA-1a in a mother with an HPA-1a1b genotype. MATERIALS AND
      METHODS: The first child of a 29-year-old mother presented with a petechial rash
      and a platelet count of 8 x 10(9) per l. Upon routine serological investigation,
      a discrepancy between the HPA-1a genotype and phenotype prompted the sequencing
      of the 15 exons of the ITGB3 (integrin beta3, GPIIIa and CD61) gene in the
      mother. RESULTS: The mother was genotypically HPA-1a1b heterozygous but
      phenotyped as HPA-1a negative. Sequencing of the ITGB3 exons confirmed HPA-1a1b
      heterozygosity, but also identified a novel single nucleotide insertion in exon
      10 leading to a frameshift and premature termination at amino acid 471 of ITGB3.
      Maternal anti-HPA-1a was detected but with a pattern typical for a low-affinity
      antibody. Three transfusions of HPA-1a and -5b negative neonatal platelet
      concentrates were required to return to a safe platelet count. CONCLUSION: A rare
      ITGB3 allele was uncovered by the investigation of a severe case of alloimmune
      thrombocytopenia in a mother with HPA-1a antibodies who genotyped as HPA-1a1b.

PMID- 18070278
TI  - Functions of red cell surface proteins.
AB  - The external membrane of the red cell contains numerous proteins that either
      cross the lipid bilayer one or more times or are anchored to it through a lipid
      tail. Many of these proteins express blood group activity. The functions of some
      of these proteins are known; in others their function can only be surmised from
      the protein structure or from limited experimental evidence. They are loosely
      divided into four categories based on their functions: membrane transporters;
      adhesion molecules and receptors; enzymes; and structural proteins that link the
      membrane with the membrane skeleton. Some of the proteins carry out more than one
      of these functions. Some proteins may complete their major functions during
      erythropoiesis or may only be important under adverse physiological conditions.
      Furthermore, some might be evolutionary relics and may no longer have significant
      functions. Polymorphisms or rare changes in red cell surface proteins are often
      responsible for blood groups. The biological significance of these polymorphisms
      or the selective pressures responsible for their stability within populations are
      mostly not known, although exploitation of the proteins by pathogenic micro
      organisms has probably played a major role.

PMID- 18070279
TI  - Human parvovirus PARV4 in clotting factor VIII concentrates.
AB  - BACKGROUND AND OBJECTIVES: Parvoviruses are small non-enveloped DNA viruses,
      relatively resistant to virus inactivation procedures. The recently identified
      human parvovirus PARV4, including a related genotype 2 virus (also termed PARV5),
      has been found to be a contaminant of pooled plasma used in the manufacture of
      plasma-derived products. This report describes an investigation to determine
      whether PARV4 is present in clotting factor concentrates. MATERIALS AND METHODS:
      Factor VIII concentrates manufactured in the past 30-35 years were screened for
      PARV4 and human parvovirus B19 (B19V) sequences. Viral loads in products testing
      positive for PARV4 were quantified using a consensus TaqMan assay designed to a
      highly conserved region. DNA sequence analysis was performed to confirm the
      genotypes present. RESULTS: From a total of 175 lots of factor VIII concentrate,
      28 of these contained PARV4 sequences, and in two lots both genotypes 1 and 2
      were found to be present. The highest viral loads observed exceeded 10(5) copies
      per ml. The majority of factor VIII concentrates testing positive for PARV4 were
      manufactured in the 1970s and 1980s. Human B19V was also a frequent contaminant
      of these products. CONCLUSIONS: PARV4 was detected in 16% of factor VIII
      concentrates, particularly in older batches from the 1970s and 1980s. The
      significance in terms of the viral safety and potential transmission to
      recipients of these products is not yet known.

PMID- 18070280
TI  - Use of capillary blood count parameters in adults.
AB  - BACKGROUND AND OBJECTIVES: Capillary samples can provide blood for cell counts in
      haematologic patients and blood donors. However, some accept only values from
      venous blood. This study compares capillary and venous blood counts to verify the
      hypothesis that they are equivalent. MATERIALS AND METHODS: We analysed 463
      capillary (fingerstick) and venous blood samples from 428 adults of both sexes
      (71% haematologic patients, 29% potential blood and apheresis donors). Both
      samples were taken at the same time from each subject. Haemoglobin (Hb),
      haematocrit (Hct), white blood cells (WBC), platelets, red blood cells (RBC),
      mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb
      concentration (MCHC) were measured using a haematology analyser (Advia 120,
      Bayer). RESULTS: Capillary Hb, Hct, WBC, RBC, MCV and MCH were all significantly
      higher than the venous values [+0.2 mmol/l (+0.3 g/dl), +0.02 l/l (+2%), +0.2 x
      10(9)/l, +0.1 x 10(12)/l, +3.1 fl and +0.01 fmol, respectively], whereas the
      capillary MCHC was lower (-0.6 mmol/l). There was no difference in platelets (-1
      x 10(9)/l). Capillary Hb and Hct values were higher in patients with anaemia and
      polycythaemia, respectively. However, no significant differences occurred in
      severe thrombocytopenia. CONCLUSION: In adult haematologic patients, however,
      only the differences in Hb and Hct values may be of clinical relevance. For
      potential blood and apheresis donors, Hb and platelet screening are equivalent
      with either capillary and venous blood using a haematology analyser.

PMID- 18070281
TI  - Why do some apheresis donors donate blood just once?
AB  - BACKGROUND AND OBJECTIVES: More knowledge about the reasons for non-return of
      blood donors (BD) would enable blood donation services (BDS) to improve the
      efficacy of recruitment and retention programmes. We interviewed returning (RBD)
      and non-returning apheresis BDs (NRBD) of our university hospital-based BDS.
      MATERIALS AND METHODS: A questionnaire was sent to 1218 individuals who passed
      the initial health check with no more than one subsequent blood donation. A
      similar questionnaire was answered by 235 randomly incoming RBDs. We asked for
      age, sex, profession, education level, motives to donate blood and, if
      applicable, reasons for non-return. These data were compared between NRBDs and
      RBDs and were analysed in relationship to the reasons for non-return. RESULTS: We
      received 267 answered questionnaires (21.9%). As 32 individuals indicated that
      they had been permanently deferred and 47 BDs had donated blood elsewhere, 188
      NRBDs remained for further analysis. We found more women than men among NRBDs.
      Medical professions were less likely to return than students and trainees.
      Individuals motivated by personal experience, remuneration or a free health check
      were more likely to return than others. Whereas logistic reasons were of highest
      relevance for non-return in general, women indicated anxiety of blood donation as
      reason for non-return more often than men. CONCLUSION: Reducing women's anxiety
      of blood donation, reminding medical professions more intensively on blood
      donation and appealing to personal experience or a free health check may be the
      most promising approaches to increase BDs' return rates.

PMID- 18070282
TI  - Granulocyte transfusions for neutropenic patients with life-threatening
      infections: a single centre experience in 47 patients, who received 348
      granulocyte transfusions.
AB  - INTRODUCTION: The role of granulocyte transfusions (GT) in patients with
      neutropenia-related infections remains controversial. MATERIALS AND METHODS: A
      retrospective analysis of 47 neutropenic patients, treated with 348 consecutive
      GTs for life-threatening infections between 1999 and 2004, is presented. RESULTS:
      The only grade III-IV toxicity observed in GT recipients was respiratory
      deterioration (n = 6, 12.8%). The overall infection-related mortality (IRM)
      approached 38%. Achievement of a neutrophil count of > 700 cells per microl after
      at least 50% of days of GTs (n = 33, 70%) significantly correlated with reduced
      IRM (27.3% vs. 64.3%, P < 0.02). GT doses of > 2 x 10(10) neutrophils per bag
      appeared to increase both neutophil and platelet counts following transfusion.
      CONCLUSION: GTs are safe and should be considered for patients with life
      threatening neutropenic infections. However, prospective randomized studies of
      GTs are the only way to establish the true role of GTs.

PMID- 18070283
TI  - Management of alloimmune thrombocytopenia.

PMID- 18070284
TI  - Hepatitis C virus: from oxygen free radicals to hepatocellular carcinoma.
AB  - Epidemiological evidence clearly identifies chronic infection with hepatitis C
      virus (HCV) as a major risk factor for the development of hepatocellular
      carcinoma (HCC). Among the mechanisms that have been implicated in the pro
      carcinogenic effect of HCV infection, an increased production of reactive oxygen
      species in the liver seems to have a major pathogenetic role in leading from
      chronic inflammation to cancer. Recent data have also demonstrated that HCV is
      capable of inducing this active production of free radicals per se, not just
      through inflammation, a feature peculiar to this virus and the specific activity
      of its core protein. This paper provides an overview of the inter-relationships
      between HCV, liver damage, free radical production and HCC, describing at least
      in part the complex network involving DNA oxidative damage, cytokine synthesis,
      proto-oncogene activation and oestrogen receptor expression, that may all be
      deeply involved in liver carcinogenesis.

PMID- 18070285
TI  - Hepatitis A seroprevalence and its relationship with environmental factors in
      children of different age groups in Kahramanmaras, Eastern Mediterranean region
      of Turkey.
AB  - Hepatitis A infections are influenced by environmental and socioeconomic factors.
      Epidemiologic studies regarding hepatitis A virus (HAV) infection in Turkey have
      not previously examined these factors. We investigated HAV seroprevalence and its
      association with sociodemographic factors among children of various ages in the
      Eastern Mediterranean region of Turkey. The study included 1142 children (603
      male and 539 female) between ages of 6 months and 18 years. Seropositivity in the
      whole group was 57.2%. HAV prevalence rates according to age groups were as
      follows: 35.5% in 6-23 months group, 19.2% in 2-5 years group, 74.3% in 6-10
      years group, 83.0% in 11-14 years group, 92.8% in 15-18 years group. Risk factors
      that influenced seropositivity were; dense population, over-crowded families,
      excessive number of siblings, low socioeconomic status and low education of the
      mother. As HAV seroprevalence in children older than 6 years of age is high, we
      recommend hepatitis A vaccination in this region after the first year of life.

PMID- 18070286
TI  - Hepatitis B virus polymerase variants associated with entecavir drug resistance
      in treatment-naive patients.
AB  - It has been suggested that lamivudine therapy can preselect for hepatitis B virus
      (HBV) variants associated with resistance to entecavir (ETV) treatment. The aim
      of this study was to determine the prevalence of HBV variants associated with ETV
      resistance (rtI169T, rtT184G, rtS202I, rtM250V) in naive patients before and
      during lamivudine therapy. This retrospective study includes 111 untreated
      patients with chronic HBV infection, who were later treated with lamivudine
      therapy for at least 18 months. Serum samples were obtained before and during
      treatment. Variants related with ETV drug resistance were analysed by sequencing
      the HBV reverse transcriptase. Prior to lamivudine treatment, three cases (2.7%)
      had substitutions in the HBV polymerase gene corresponding to variants associated
      with ETV resistance (rtS202S/I). None of these patients had lamivudine-resistant
      variants. During lamivudine treatment, substitutions associated with ETV
      resistance were detected in 10 (9%) nonresponding patients who had not presented
      these changes before treatment. In 2/10 cases, these changes were observed before
      detection of lamivudine-resistant substitutions. In 10 of 12 nonresponders, one
      of them with ETV-related variants prior to treatment, these variants persisted to
      the end of therapy. Detection of variants related to ETV drug resistance in
      untreated patients with chronic HBV infection indicates that these variants are
      present in a significant proportion of the HBV quasispecies. This fact, as well
      as the emergence of ETV-resistant variants during lamivudine treatment, should be
      kept in mind when selecting candidates for ETV therapy.

PMID- 18070287
TI  - Association of HLA-DRB1*13 and TNF-alpha gene polymorphisms with clearance of
      chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai
      population.
AB  - Considerable evidence suggests that host genetic factor play an important role in
      the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV)
      infection in several ethic groups. Association study was performed included 150
      chronic HBV patients, 100 resolved hepatitis B and 150 healthy individuals with
      similar ethic background. Interestingly, human leucocyte antigen (HLA)-DR13 show
      a strong association with the clearance of HBV [odds ratio (OR) = 0.04, 95%
      confidence interval (CI) = 0.00-0.26, corrected P-value (P(c)) = 0.0008] similar
      to reports from several ethic groups. TNF-alpha promoter polymorphisms (-863, 
      308 and -238) were also analysed. Only -863 C allele was found to be
      significantly decreased in chronic HBV patients compared with healthy control
      (P(c) = 0.03, OR = 0.54, 95% CI = 0.35-0.84 respectively). This -863C allele was
      not in linkage disequilibrium with HLA-DR13 suggesting that other genetic markers
      linked with -863C might influence clearance of chronic HBV infection in Thai.
      When stratified chronic HBV patients into patients without hepatocellular
      carcinoma (HCC) and with HCC, the -863 A allele was significantly increased in
      the HCC group compared to healthy control (P(c) = 0.003, OR = 2.61, 95% CI = 1.49
      4.60). Haplotype analysis (-863/-308/-238) revealed that the homozygosity of the
      haplotype (CGG/CGG) was a protective marker for HCC (OR = 0.37, 95% CI = 0.17
      0.79, P(c) = 0.02). One can propose that carriers of -863A genotype are
      associated with increased levels of TNF-alpha in the liver in response to HBV
      infection and induce hapatocyte damage that may finally lead to HCC development.
      Additional study is needed to validate these finding and to further explore the
      genetic pathogenesis of HBV infection.

PMID- 18070288
TI  - Hepatitis C virus E2 envelope protein induces dendritic cell maturation.
AB  - Maturation is a critical process for dendritic cells (DC) to gain or enhance
      their functions in antigen presentation and T-cell activation. In this study, we
      investigated the effect of hepatitis C virus (HCV) envelope protein E2 on DC
      maturation and related functions. We show that binding of E2 protein to DC leads
      to a change from immature to mature phenotype as detected by an increased
      expression of cell surface molecules including CD83, CD80, CD86, CD11c and MHC
      class II. The E2-matured DC showed higher capacity to stimulate T-cell
      proliferation and interferon-gamma production and displayed higher levels of
      interleukin-12 production when compared with immature DC. The induction of DC
      maturation by E2 is both time- and dose-dependent and can be inhibited by anti-E2
      antibodies. In addition, DC matured by E2 showed decreased uptake of bovine serum
      albumin and latex beads, indicating their decreased activities of endocytosis and
      phagocytosis upon maturation. Taken together, our results demonstrated that E2
      protein is able to induce dendritic cell maturation and suggested that E2 protein
      may play an important role in regulation of immune responses during HCV
      infection.

PMID- 18070289
TI  - Identification of liver fibrosis in HIV/HCV-coinfected patients using a simple
      predictive model based on routine laboratory data.
AB  - We constructed noninvasive models to predict significant fibrosis (F > or = 2)
      and advanced fibrosis (F > or = 3) among human immunodeficiency virus
      (HIV)/hepatitis C virus (HCV)-coinfected patients, naive for anti-HCV treatment.
      A total of 296 patients with liver biopsy were randomly assigned to an estimation
      group (EG = 226; 70%) and a validation group (VG = 70; 30%). We developed the
      Hospital Gregorio Maranon (HGM)-1 index, based on platelet count, aspartate
      aminotransferase (AST) and glucose, to predict F > or = 2 and the HGM-2 index,
      based on platelet count, international normalized ratio, alkaline phosphatase and
      AST to predict F > or = 3. The area under the receiver operating characteristic
      curves (AUROCs) of the HGM-1 index for the EG and the VG were 0.807 and 0.712
      respectively. The AUROCs of the HGM-2 index for the EG and the VG were 0.844 and
      0.815 respectively. With the HGM-1 index applied to the VG, using best cutoff
      scores, the negative predictive value (NPV) to exclude F > or = 2 was 54.5% and
      the positive predictive value (PPV) to confirm F > or = 2 was 93.3%. With the HGM
      2 index applied to the VG, using best cutoff scores, the NPV to exclude F > or =
      3 was 92.3, and the PPV to confirm F > or = 3 was 64.3%. Thus, HGM-2 accurately
      predicted F > or = 3 among HIV/HCV-coinfected patients. HGM-1 was less accurate
      at predicting F > or = 2.

PMID- 18070290
TI  - Comparison of deaths related to Hepatitis C and AIDS in Scotland.
AB  - In resource-rich countries, the incidence of and mortality from AIDS has fallen
      dramatically since the introduction of combination antiretroviral therapy. In
      contrast, developed countries have observed increases in the public health burden
      associated with the hepatitis C virus (HCV). We compared past and current trends
      in mortality related to HCV sequelae and HIV/AIDS in Scotland by linking death
      records with national databases of persons diagnosed with HCV and HIV/AIDS. AIDS
      related deaths increased rapidly during the late-1980s to mid-1990s and declined
      dramatically after 1996. Deaths related to HCV (i.e., viral hepatitis, liver
      cancer, alcoholic liver disease, or non-alcoholic liver disease) surpassed the
      number of AIDS-related deaths in 1998 and increased at an average annual rate of
      10.5% (95% confidence interval = 7-14%) during 1996-2005. The leading underlying
      cause of HCV-related deaths was alcoholic liver disease (50% of deaths during
      2001-2005). This study highlights the increasing public health burden, vis-a-vis
      mortality, of HCV, when compared with HIV/AIDS in developed countries. Increased
      diagnosis and treatment of eligible HCV-infected individuals will be required if
      we wish to mitigate the future impact of HCV morbidity and mortality.

PMID- 18070291
TI  - Therapy expectations and physical comorbidity affect quality of life in chronic
      hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection is associated with a significant reduction of
      health related quality of life (QOL), the causes and mechanisms of which are
      still unknown. To explore whether treatment history could affect QOL, we examined
      patients with detectable HCV viraemia who had a different therapeutic background.
      Two hundred sixty-four consecutive subjects with chronic HCV infection and
      detectable viraemia were enrolled. Of these, 163 were untreated patients, 43 were
      relapsers, 58 were nonresponders (NR) to nonpegylated interferon (IFN) therapy.
      To assess QOL, three self-report instruments were employed: the Short Form-36 (SF
      36), the Chronic Liver Disease Questionnaire (CLDQ-I) and the World Health
      Organization Quality of Life assessment (WHOQOL-BREF). Clinical and demographic
      data were collected, and the QOL scores of HCV-positive patients were compared
      with those of an Italian normative sample and healthy controls. Further antiviral
      treatment was offered to untreated and relapsed patients but not to NR. All
      patient groups displayed lower QOL scores compared with the normative sample and
      controls. NR displayed lower QOL scores in several areas compared with untreated
      patients and relapsers. In multivariate regression analyses, being NR and having
      a physical comorbidity were significantly associated with poorer QOL.
      CONCLUSIONS: Treatment history and expectations and physical comorbidity may
      affect QOL in HCV-positive patients. Untreated and relapsed patients have
      comparable levels of QOL and higher scores than NR.

PMID- 18070292
TI  - Views of hepatitis C virus patients delayed from treatment for psychiatric
      reasons.
AB  - For patients with chronic hepatitis C virus, certain psychiatric disorders are
      contraindications for antiviral therapy with interferon-alpha (IFN). Although
      these conditions delay a significant portion of patients from beginning therapy,
      no one has yet portrayed the views of these patients. A qualitative analysis,
      drawing upon semi-structured interviews, was developed to generate hypotheses
      regarding patient views of the treatment disposition process, and to generate
      strategies for increasing the portion of treatment-eligible patients. Two focus
      groups were conducted: one for patients delayed from treatment due to current or
      recent depression, and one for patients delayed due to current or recent alcohol
      use. A grounded theory analysis of the interview data were conducted. Patients
      were generally satisfied with the decision-making process, based largely on
      education from, and trust in, physicians. Upon learning their diagnosis, patients
      reported making healthy behaviour changes regarding alcohol, diet, exercise and
      herbal remedies. Some patients reported that requiring a period of alcohol
      abstinence was excessive, as they believed that they could discontinue alcohol
      use immediately, if so instructed by a physician. Patients seemed to over
      interpret the likelihood of suicide during interferon-alpha (IFN) therapy.
      Current or recent psychiatric morbidity delays many patients from beginning
      interferon therapy. Nonetheless, this may be an optimal time for physicians to
      encourage healthy behaviours including abstinence from alcohol. Also, physicians
      may need to extensively assess the use of herbal remedies by patients. To help
      patients make judgments about beginning therapy, physicians should focus upon
      risk communication regarding the likelihood of suicide on therapy with
      interferon.

PMID- 18070293
TI  - Co-morbid medical and psychiatric illness and substance abuse in HCV-infected and
      uninfected veterans.
AB  - Comorbidities may affect the decision to treat chronic hepatitis C virus (HCV)
      infection. We undertook this study to determine the prevalence of these
      conditions in the HCV-infected persons compared with HCV-uninfected controls.
      Demographic and comorbidity data were retrieved for HCV-infected and -uninfected
      subjects from the VA National Patient Care Database using ICD-9 codes. Logistic
      regression was used to determine the odds of comorbid conditions in the HCV
      infected subjects. HCV-uninfected controls were identified matched on age,
      race/ethnicity and sex. We identified 126 926 HCV-infected subjects and 126 926
      controls. The HCV-infected subjects had a higher prevalence of diabetes, anaemia,
      hypertension, chronic obstructive pulmonary disease (COPD)/asthma, cirrhosis,
      hepatitis B and cancer, but had a lower prevalence of coronary artery disease and
      stroke. The prevalence of all psychiatric comorbidities and substance abuse was
      higher in the HCV-infected subjects. In the HCV-infected persons, the odds of
      being diagnosed with congestive heart failure, diabetes, anaemia, hypertension,
      COPD/asthma, cirrhosis, hepatitis B and cancer were higher, but lower for
      coronary artery disease and stroke. After adjusting for alcohol and drug abuse
      and dependence, the odds of psychiatric illness were not higher in the HCV
      infected persons. The prevalence and patterns of comorbidities in HCV-infected
      veterans are different from those in HCV-uninfected controls. The association
      between HCV and psychiatric diagnoses is at least partly attributable to alcohol
      and drug abuse and dependence. These factors should be taken into account when
      evaluating patients for treatment and designing new intervention strategies.

PMID- 18070294
TI  - Discarding the baby with the bathwater.

PMID- 18070295
TI  - Use of an intracardiac electrogram eliminates the need for a surface ECG during
      implantable cardioverter-defibrillator follow-up.
AB  - BACKGROUND: A surface electrocardiogram (SECG) for pacing threshold measurements
      during routine implantable cardioverter-defibrillator (ICD) follow-up can be
      cumbersome. This study evaluated the use of an intrathoracic far-field
      electrogram (EGM) derived between the Can and superior vena cava (SVC) electrode 
      - the Leadless electrocardiogram (LLECG), in dual chamber ICDs in performing
      pacing threshold tests. METHODS: The LLECG was evaluated prospectively during
      atrial and ventricular pacing threshold testing as a substudy of the Comparison
      of Empiric to Physician-Tailored Programming of Implantable Cardioverter
      Defibrillators trial (EMPIRIC) in which dual chamber ICDs were implanted in 888
      patients. Threshold tests were conducted at 1 volt by decrementing the pulse
      width. Follow-up at three months compared pacing thresholds measured using LLECG
      with those using Lead I of the surface ECG (SECG). The timesaving afforded by
      LLECG was assessed by a questionnaire. RESULTS: The median threshold difference
      between LLECG and SECG measurements for both atrial (0.00 ms, P = 0.90) and
      ventricular (0.00 ms, P = 0.34) threshold tests were not significant. Ninety
      percent of atrial and ventricular threshold differences were bounded by +/- 0.10
      ms and -0.10 to +0.04 ms, respectively. We found that 99% of atrial and
      ventricular thresholds tests at six and 12 months attempted using LLECG were
      successfully completed. The questionnaire indicated that 65% of healthcare
      professionals found LLECG to afford at least some timesaving during device follow
      ups. CONCLUSION: Routine follow-up can be performed reliably and expeditiously in
      dual chamber Medtronic (Minneapolis, MN, USA) ICDs using LLECG alone, resulting
      in overall timesaving.

PMID- 18070296
TI  - Current of injury predicts acute performance of catheter-delivered active
      fixation pacing leads.
AB  - BACKGROUND: During pacemaker lead (PPML) implantation, the implanter must assess
      lead stability (fixation) and pacing threshold adequacy. Implanters rely
      principally on lead impedance (IMP) and pacing threshold measurements after
      fixation of the PPML to determine adequacy of pacing sites. Continuously
      monitoring lead parameters during fixation might better identify predictors of
      acute lead stability and performance. METHODS: At the time of PPML implantation
      with a catheter delivered, fixed screw, 4-Fr PPML (Medtronic 3830, Minneapolis,
      MN, USA) patients underwent measurements of R-wave amplitude, slew rate, and
      current of injury (COI) (maximum and at 80 ms) during each turn of the helix.
      Lead stability was tested with traction applied to the lead body. RESULTS:
      Eighteen patients (age 70 +/- 9 years, 9 males) were studied. Right ventricular
      lead positioning was attempted 43 times; 26 positions demonstrated good fixation
      and 18 had satisfactory threshold. Sites of good fixation consistently showed
      larger COI (maximum and at 80 ms) compared to poor fixation sites throughout each
      turn of the helix; R wave, slew rate, and IMP did not differ significantly. When
      all measures of COI were examined in a stepwise regression model only the final
      measure of COI at 80 ms proved significantly associated with acute stability (P =
      0.032). CONCLUSIONS: Lead stability and threshold adequacy are predictable from
      assessment of the magnitude of injury current. Continuous monitoring of lead
      parameters during fixation does not appear to confer any benefit over assessment
      of the parameters after final rotation of the lead. A negative COI is associated
      with poor threshold and/or fixation.

PMID- 18070297
TI  - Atrial threshold variability: implications for automatic atrial stimulation
      algorithms.
AB  - BACKGROUND: Automatic management of atrial stimulation by verification of atrial
      threshold (ACM) has recently been made feasible. We investigated circadian atrial
      threshold variability over the long term and the predictors of successful
      automatic atrial threshold measurement, in order to provide practical clues for
      programming ACM features, in such a way as to achieve daily threshold
      verification and > 99% effective atrial stimulation. METHODS: Six daily attempts
      to measure atrial threshold were programmed in patients receiving an EnPulse
      pacemaker (Medtronic Inc., Minneapolis, MN, USA). Atrioventricular (AV)
      conduction was maximized by programming Search AV+ (SAV+) to a resting Paced AV
      delay = 400 ms in the first month, and 600 ms thereafter. RESULTS: Seventy-six
      patients had a median follow-up of 12 months. Median ACM success was 77%.
      Concordance between automatically and manually measured thresholds was observed
      during the entire follow-up (Rho = 0.82, P < 0.001). Daily variability in atrial
      threshold was < 0.5 V in > 94% of measurements in the first trimester after
      implantation, and < 0.5 V in > 99% of measurements thereafter, as well as any
      time after pacemaker replacement. Atrial threshold was measured on 86% of days:
      the predictors of ACM failure were AV block (AVB), high%Atrial pacing, and atrial
      fibrillation. Programming SAV+ to achieve 600 ms resting Paced AV
      decreased%Vpacing in patients with normal AV conduction and first-degree AVB,
      improving the ability to detect atrial threshold. CONCLUSIONS: The reliability of
      ACM is high over a long follow-up. On the basis of atrial threshold variability,
      a practical approach to ACM programming should be two daily atrial threshold
      measurements in patients with normal AV conduction and%Ap < or = 40%, or with
      normal sinus activity and AVB, whereas 3-4 measurements should be recommended in
      patients with first-degree AVB and%Ap > 40% or with recurrent atrial fibrillation
      and AVB. The lowest adapted stimulation output should achieve at least threshold
      +1 V in the first trimester after implantation, then threshold +0.5 V thereafter,
      in order to achieve > 99.5% effective atrial stimulation.

PMID- 18070298
TI  - Morphology-enhanced atrial event classification improves sensing in pacemakers.
AB  - BACKGROUND: In atrial-based pacing, appropriate therapy and reliable diagnostics
      depend on detection and discrimination of atrial signals. Accurate classification
      of atrial events is mainly confounded by oversensing of ventricular far-field R
      wave signals (FFRW), but attempts to reject FFRWs by manipulating atrial
      sensitivity and/or postventricular atrial blanking period (PVAB) may result in
      undersensing (especially of atrial fibrillation, AF) or in 2:1 atrial flutter
      detection. The objective of this study is therefore to evaluate if such methods
      can be improved by morphology-enhanced atrial event classification (MORPH).
      METHODS: Twenty-four-hour ambulatory atrial electrograms were recorded from
      continuous telemetry of digital pacemakers. Half of the recording was used for
      collecting two individual morphology parameters that discriminated P-waves from
      FFRWs in every patient (learning phase). The other half was used to test the
      MORPH algorithm against traditional methods (classification phase). RESULTS: In
      44/48 patients, data were suitable for analysis. Average P and FFRW amplitudes
      were 1.96 mV versus 0.61 mV (P < 0.001). The interval between ventricular events
      and FFRW oversensing (VA interval) averaged at 14 ms during sensing and at 118 ms
      during pacing in the ventricle. Compared to nominal ("Factory") settings, the
      MORPH algorithm improved the sensitivity for P-wave recognition from 97.2% to
      99.2%, the specificity from 91.9% to 99.96%, and the accuracy from 95.3% to 99.4%
      (P < 0.01 for all). CONCLUSIONS: By improving atrial signal discrimination,
      morphology analysis of atrial electrograms allows for high atrial sensitivity
      settings, and potentially improves the reliability of atrial arrhythmia
      diagnostics in heart rhythm devices.

PMID- 18070299
TI  - Left ventricular endocardial pacing: a transarterial approach.
AB  - INTRODUCTION: We tested the feasibility of a new technique of direct left
      ventricular endocardial lead placement across the aortic valve in a chronic (six
      month) pig model. The potential for aortic valve damage, systemic embolization,
      and pacing lead maturation and function within the left ventricle are unknown.
      METHODS: Ten minipigs were successfully implanted with a transaortic left
      ventricular lead (Medtronic CapSureFix, Minneapolis, MN, USA) placed in the left
      ventricular apex via the carotid artery. Each pig received either a polyurethane
      (n = 5) or silicone (n = 5) lead. Post implant each pig received clopidogrel and
      aspirin for seven days. After six months all surviving pigs underwent thorough
      necropsy. RESULTS: Each pig had adequate sensing (12.1 +/- 4 mV) and pacing
      thresholds (0.79 +/- 0.2 @ 0.5 V) at implant. Postoperatively two pigs died of a
      respiratory illness. One pig died postoperatively due to sepsis. At the six-month
      follow-up, all surviving pigs (n = 7) were in a healthy state. Of the pigs
      without dislodgement (n = 5) there was adequate sensing, but a rise in pacing
      thresholds. Echocardiography revealed a normal ejection fraction and only trace
      to mild aortic insufficiency in all pigs. Of the seven surviving pigs there were
      no thromboembolic events noted. One silicone lead was noted to have thrombosis
      along the lead screw and shaft. CONCLUSION: Direct transaortic placement of a
      left ventricular lead is feasible. After six months, there was no significant
      aortic regurgitation and no evidence of thromboembolism despite no
      anticoagulation. Lead function was acceptable and only one silicone lead (and no
      polyurethane lead) was noted to have significant thrombosis.

PMID- 18070300
TI  - Transthoracic versus transesophageal cardioversion of atrial fibrillation under
      light sedation: a prospective randomized trial.
AB  - BACKGROUND: Electrical cardioversion (ECV) of atrial fibrillation (AF) is limited
      by a 5-10% failure rate and by the expense arising from a perceived need for
      general anesthesia. A transesophageal approach using light sedation has been
      proposed as a means of augmenting the success rate and avoiding the need for
      general anesthesia. We hypothesized that the high rate of success and the lower
      energy requirement associated with biphasic cardioversion might eliminate any
      advantage of the transesophageal approach. METHODS: We randomly assigned 60
      patients attending for ECV of persistent AF to a transesophageal or a
      transthoracic approach. Sedation of moderate depth was achieved with intravenous
      midazolam. The dose of midazolam was titrated in the same manner in both groups.
      RESULTS: Sinus rhythm was restored in 29/30 patients (97%) in each group using a
      similar number of shocks for both groups (1.3 +/- 0.6 transesophageal vs 1.4 +/-
      0.7 transthoracic, P = NS) with a similar procedure duration (14.1 +/- 8.2
      minutes vs 13.8 +/- 7.5 minutes, P = NS). Both groups received similar doses of
      midazolam (4.2 +/- 2.7 mg vs 4.4 +/- 2.8 mg, P = NS) and both reported a similar
      discomfort score in (0.9 +/- 1.3 vs 1.1 +/- 1.8, P = NS). No complication
      occurred in either group. CONCLUSION: AF may be cardioverted safely and
      effectively by either a transthoracic or a transesophageal approach. The use of
      sedation of moderate depth renders cardioversion by either approach acceptable.
      As transesophageal ECV shows no clear advantage, transthoracic cardioversion
      should remain the approach of first choice.

PMID- 18070301
TI  - Accelerometer-derived time intervals during various pacing modes in patients with
      biventricular pacemakers: comparison with normals.
AB  - INTRODUCTION: Changes due to biventricular pacing have been documented by
      shortening of QRS duration and echocardiography. Compared to normal ventricular
      activation, the presence of left bundle branch block (LBBB) results in a
      significant change in cardiac cycle time intervals. Some of these have been used
      to quantify the underlying cardiac dyssynchrony, assess the effects of
      biventricular pacing, and guide programming of ventricular pacing devices. This
      study evaluates a simple noninvasive method using accelerometers attached to the
      skin to measure cardiac time intervals in biventricularly paced patients.
      METHODS: Ten patients with biventricular pacemakers previously implanted for
      congestive heart failure were paced in the AAI mode, then in atrioventricular
      (AV) sequential mode from the right and left ventricles followed by biventricular
      pacing. Simultaneous recordings were obtained by 2D, Doppler echocardiography as
      well as by accelerometers. Similar recordings were obtained from 10 gender, aged
      matched, normal controls during sinus rhythm. RESULTS: Compared to normals, heart
      failure patients paced in AAI mode had prolonged isovolumetric contraction time
      (IVCT), shorter ventricular ejection time (LVET), and prolonged isovolumetric
      relaxation (IVRT). With biventricular pacing the IVCT decreased, but the LVET and
      IVRT did not change significantly. There was excellent correlation between the
      echo and accelerometer-measured intervals. CONCLUSIONS: Shortening of the IVCT
      measured by an accelerometer is a consistent time interval change due to
      biventricular pacing that probably reflects more rapid acceleration of left
      ventricular ejection. The accelerometer may be useful to assess immediate
      efficacy of biventricular pacing during device implantation and optimize
      programmable time intervals such as AV and interventricular (VV) delays.

PMID- 18070302
TI  - Correlation between QTc interval and clinical severity of subarachnoid hemorrhage
      depends on the QTc formula used.
AB  - OBJECTIVES: Subarachnoid hemorrhage (SAH) frequently prolongs QT interval in the
      acute phase. The purpose of our study is to investigate whether the correlation
      between electrocardiographic corrected QT interval and the clinical severity of
      SAH depends on QTc formula used. METHODS: We retrospectively studied 52
      consecutive subjects with nontraumatic SAH (extravasation of blood into the
      spaces covering the central nervous system that are filled with cerebrospinal
      fluid) who were admitted within the first day of SAH. QT intervals were measured
      on a standard 12-lead electrocardiography and corrected by Bazett and Hodges
      formulae. All patients were evaluated according to clinical condition on
      admission by Hunt-Hess grades. The patients were grouped in two different
      categories according to QT interval corrected by Bazett and Hodges and scored by
      Hunt-Hess (HH) grades. RESULTS: Mean age of the study patients was 54 +/- 12
      years and of those 31 (60%) were female. Mean values of heart rate and RR
      interval were 82 +/- 21 bpm and 777 +/- 163 msec, respectively. The mean QTc
      interval by Bazett and Hodges were 456 +/- 59 msec and 438 +/- 48 msec,
      respectively (P < 0.001). Twenty-three patients according to Bazett and fifteen
      according to Hodges had prolonged QTc. Correlation analyses showed relation
      between HH and QTc and prolonged QTc by Bazett (r = 0.278, P = 0.04 and r =
      0.314, P = 0.024; respectively). There was no correlation between HH and QTc and
      prolonged QTc by Hodges (r = 0.204, P = 0.14 and r = 0.115, P = 0.41;
      respectively). CONCLUSIONS: In our study, correlation between QTc interval and
      clinical severity of SAH depended on the QTc formula used.

PMID- 18070303
TI  - Comparison of microvolt T-wave alternans measurements using atrial pacing
      compared to atropine administration.
AB  - BACKGROUND: Microvolt T-wave alternans (MTWA) has been associated with malignant
      ventricular arrhythmias in patients (pts) with structural heart disease. MTWA has
      been shown to be a strong heart rate-dependent arrhythmia marker. However, in
      clinical practice some pts in which MTWA should be assessed are unable to perform
      physical exercise to increase heart rate due to various reasons. METHODS: In this
      study, we investigated the feasibility of noninvasive MTWA measurement by using
      intravenous atropine to increase heart rate and compared the results to MTWA
      measurement by right atrial (RA) pacing during electrophysiologic (EP) study in
      27 consecutive pts (53 +/- 14 years; nine women). Determining the arrhythmia
      event-rate, a follow-up of 18 months was performed in all pts. RESULTS: Using
      atropine, five pts (18%) did not reach the target heart rate (105 bpm). In the
      remaining group of pts, concordant results for MTWA assessment could be found in
      21 pts (96%). Comparing MTWA positive tests there were slightly higher amplitudes
      using right atrial (RA) pacing than atropine (7.0 +/- 2.3 microV vs 6.3 +/- 2.2
      microV, P = 0.03; r = 0.97). During follow-up all pts with a positive MTWA test
      had documented ventricular arrhythmias. There were no arrhythmic events in the
      MTWA negative group. CONCLUSION: Whenever target heart rate for MTWA evaluation
      is obtained by intravenous atropine, the results are comparable to RA pacing. In
      using atropine there has been observed no pharmacologically influenced increase
      of MTWA voltage leading to false positive MTWA results. Therefore the use of
      atropine can be recommended as a safe, non-invasive, and reliable method for MTWA
      assessment.

PMID- 18070304
TI  - Exercise does not increase QTcmax and QTcd in diabetic patients with autonomic
      neuropathy.
AB  - BACKGROUND: The purpose of this study was to examine the effects of exercise on
      maximum QTc interval (QTcmax) and QTc dispersion (QTcd) in diabetic patients
      without clinically evident heart disease. METHODS: Seventy-six diabetic patients
      who had no coronary artery disease or hypertension (group I; mean age 48 +/- 9
      years old) and 40 healthy volunteers (group II; mean age 46 +/- 13 years old)
      were enrolled in the study. Cases with clinically evident heart disease were
      excluded from the study. Resting 12-lead electrocardiogram (ECG) and maximal
      treadmill exercise test (according to Bruce protocol) were performed in all
      cases. The QTcmax interval was determined at rest (RQTcmax) and during peak
      exercise (PQTcmax). Also, the QTcd was measured at rest (RQTcd) and during peak
      exercise (PQTcd). Autonomic neuropathy was assessed by measuring the heart rate
      variability (HRV). RESULTS: There was no significant difference between clinical
      characteristics of two groups. In group I, HRV parameters were significantly
      lower than group II. RQTcd, PQTcd, RQTcmax, and PQTcmax were significantly longer
      in group I (56 +/- 16 vs 34 +/- 11; P< 0.001, 62 +/- 22 vs 40 +/- 15; P < 0.001,
      respectively). In diabetic patients, there was no significant difference between
      RQTcmax and PQTcmax (428 +/- 19 vs 420 +/- 31; P > 0.05), and no significant
      difference was present between RQTcd and PQTcd (56 +/- 16 vs 62 +/- 22; P > 0.05,
      respectively). CONCLUSION: Exercise does not affect QTcd in patients with
      diabetes mellitus and without clinically evident heart disease.

PMID- 18070305
TI  - Tilt training: does it have a role in preventing vasovagal syncope?
AB  - BACKGROUND: Vasovagal syncope is one of the most common medical conditions in
      young adults. Previous trials have shown effectiveness of tilt training in
      treating this condition. We conducted a prospective, randomized study in order to
      evaluate the role of tilt-training in young adults with vasovagal syncope.
      METHODS: Forty-six soldiers (mean age 19.4 +/- 0.8 years, 25 males), with a
      clinical diagnosis of vasovagal syncope supported by positive tilt test, were
      randomized to either three months of daily tilt training (treatment group), or no
      training (control group). Patients in both groups were instructed to increase
      fluid and salt intake, and to refrain from syncope-inducing situations, such as
      prolonged standing. RESULTS: Compliance, defined as performing 50% or more of the
      tilt training daily sessions, was 91% during the first month, and declined to 58%
      during three months. Treatment group patients had a median (interquartile range)
      of 5.0 (0.5-16.0) syncope episodes during one-year follow up, compared to a
      median of 2.0 (0-6.0) episodes in the control group (P = 0.737). Also, there was
      no difference in time to first syncope after randomization between groups: a
      median of 1.0 (0.5-2.0) month in the treatment group, compared to 0.8 (0.5-2.0)
      month in the control group (P = 0.336). CONCLUSIONS: Adding daily three-month
      tilt training to modifications in lifestyle does not improve treatment results in
      young adults with vasovagal syncope. Good compliance is difficult to achieve in a
      tilt training program.

PMID- 18070306
TI  - Does the age affect the fluoroscopy-guided transseptal puncture in catheter
      ablation of atrial fibrillation?
AB  - BACKGROUND: The anatomical differences with age may raise difficulty in
      determining the proper positioning of the transseptal puncture site in the
      therapeutic left heart catheterization. This study investigated whether age
      affects the fluoroscopy-guided transseptal puncture in the catheter ablation of
      atrial fibrillation. METHODS AND RESULTS: Fifty patients (52 +/- 12 years, 35
      men) who underwent ablation for paroxysmal/persistent atrial fibrillation were
      included. The patients were divided into two groups according to their age (cut
      point 50 y/o): young group (n = 20) and old group (n = 30). In the 30 degrees
      right anterior oblique view (RAO), the width between the transseptal puncture
      site and coronary sinus ostium (H (N-CSO)) was longer in old-age group (14.4 +/-
      9.4 vs 10.9 +/- 10.4 mm, P = 0.034). In the 60 degrees left anterior oblique view
      (LAO) view, the angle of the direction of the transseptal needle (N-angle) was
      less in the old-age group (56.0 +/- 10.0 degrees vs 58.4 +/- 9.8 degrees , P =
      0.041). The ratio of the transseptal puncture site-coronary sinus ostium (CSO)
      distance over the distance between the superior vena cava-right atrial junction
      and CSO (V(N-CSO)/V(J-CSO)) was significantly higher in the old-age group (0.73
      +/- 0.12 vs 0.63 +/- 0.2, P = 0.009). CONCLUSION: The transseptal puncture site
      in the RAO view moved higher and more posterior and the transseptal puncture
      angle in the LAO view decreased with age. These findings highlight the influence
      of age on the atrial anatomy and transseptal puncture site.

PMID- 18070307
TI  - Spatial and topologic distribution of verapamil-sensitive atrial tachycardia
      originating from the vicinity of the atrioventricular node.
AB  - BACKGROUND: Little information exists regarding the precise distribution of
      verapamil-sensitive atrial tachycardia originating from the vicinity of the
      atrioventricular node (V-AT). METHODS: In 12 patients with V-AT, we examined the
      spatial and topologic distribution of tachycardia origin relative to the His
      bundle (HB) site. The V-AT origin was divided into six areas: anterior (A-HB),
      posterior (P-HB), superior (S-HB), inferior (I-HB), lateral (L-HB), and septal
      (SP-HB) portion of HB catheter. Three dimensional distance between the distal
      pair of the electrodes of HB catheter and that of V-AT origin (DIS) was obtained
      by calculating the distances on the right and left anterior fluoroscopic images.
      Topologic distribution was expressed as the interval between the onset of the
      atrial electrogram of V-AT origin and that of HB catheter (INT). RESULTS: The
      tachycardia origin was observed at the P-HB in four, S-HB in two, I-HB in two, SP
      HB in three, and L-HB in one patient. The tachycardia cycle length, DIS, and INT
      were 369 +/- 67 ms, 12 +/- 3 mm, and -12 +/- 8 ms, respectively. After successful
      ablation of initial V-AT (1st V-AT), V-AT with a different origin (2nd V-AT) was
      induced in five patients. The tachycardia origin, tachycardia cycle length, DIS,
      and INT of the 2nd V-AT (P-HB in three, S-HB in one, and SP-HB in one patient;
      333 +/- 66 ms, 8 +/- 3 mm, and -11 +/- 4 ms, respectively) were not different
      from those of 1st V-AT. CONCLUSIONS: V-AT often shows a shift in tachycardia
      origin to another site where the spatial and topologic distributions are similar
      to those of 1st V-AT.

PMID- 18070308
TI  - Two cases of short QT interval.
AB  - BACKGROUND: The epidemiology of short QT interval remains unclear. We attempted
      to determine the incidence and clinical characteristics of short QT interval in a
      longitudinal cohort study. METHODS: A total of 19,153 subjects (7,525 male,
      11,628 female) were enrolled in the study and all available electrocardiograms
      (ECGs) were investigated longitudinally from 1958 through 2003. We defined short
      QT interval as QTc of less than 350 ms. RESULTS: Of the 19,153 subjects, two met
      the criteria of short QT interval and allowed for prevalence and incidence
      estimates for short QT interval as 0.01% and 0.39/100,000 person-years,
      respectively. Both cases had neither a family history of sudden cardiac death,
      nor a history of drug use that might have affected for QT interval. Case 1 was a
      female with history of ischemic heart disease. Case 2 was a 60-year-old male who
      exhibited a short QT interval for the first time when he was 26 years of age. He
      had sick sinus syndrome as an underlying heart disease. CONCLUSIONS: Of the
      19,153 subjects in this study, none were identified as having the short QT
      syndrome, with associated high risk of ventricular tachyarrhythmia, atrial
      fibrillation, and sudden death. Two subjects were identified as having QTc of
      less than 350 ms, and allowed prevalence and incidence estimates to be made of
      short QT interval. There observations were suggestive of clinical relationships
      between short QT interval and organic or electrophysiological heart disease.

PMID- 18070309
TI  - Acute conversion of persistent atrial fibrillation during dofetilide initiation.
AB  - BACKGROUND: Dofetilide (D) is a highly selective blocker of the rapid component
      of the delayed rectifier potassium current and was approved for the treatment of
      atrial fibrillation (AF) based on a satisfactory safety/efficacy profile from
      trials in patients with left ventricle (LV) dysfunction or heart failure. The
      dose-dependant acute conversion rates (<72 hours) were reported to be in the
      range of 6-30%. We hypothesized that the acute pharmacological conversion rate of
      D is higher than previously reported if used in a healthier cohort of patients
      with persistent AF. METHODS AND RESULTS: Eighty consecutive patients received D
      dosing per Cockroft-Gault adjustment for creatinine clearance and QTc intervals.
      Patients were 61 +/- 10 years, 79% male, ejection fraction (EF) 53 +/- 13%,
      coronary artery disease 20%, and left atrial dimension 4.1 +/- 0.2 cms. The
      duration of the treated AF episode was a median of 19 days (range 10-113 days).
      All patients received D while on telemetry for at least six dosing intervals.
      After 2.2 +/- 1.2 doses, 77% of patients converted to sinus rhythm (SR) and 23%
      did not and required direct current (DC) cardioversion. Acute pharmacological
      conversion rates were: 20% for D 125 mcg bid, 44% for 250 mcg bid, and 85% for
      500 mcg bid. None of the patients had torsade de pointes and none had to stop D
      for intolerance. Failure to convert to SR on D alone was associated with larger
      left atrium (LA) diameter (P = 0.04), longer duration of AF (P = 0.02), and use
      of lower dosages of D (P = 0.04). CONCLUSIONS: D had an unusually high
      pharmacological conversion rate, demonstrated an incremental dose response, and
      was well tolerated and safe, in a relatively healthy adult cohort with persistent
      AF. In addition to D dose, pharmaco-conversion was predicted by LA size and AF
      duration. D is a desirable alternative for conversion of AF in a variety of
      clinical settings.

PMID- 18070310
TI  - Axillary/subclavian vein puncture using navigation by parallax with an imaginary
      target.
AB  - BACKGROUND: The parallax principles allow the relative positions of two
      overlapping objects with respect to the receiver of a two dimensional image to be
      determined, and can reliably navigate an object to a target in three dimensional
      space. Navigation by parallax can direct axillary/subclavian vein puncture under
      fluoroscopy with a guide wire inside the vein. The axillary/subclavian vein has a
      constant relationship with the first rib and an imaginary target just cranial and
      lateral to the middle part of the first rib may serve as a surrogate position
      marker for the vein adequate for guiding puncture. METHOD: Patients requiring
      axillary/subclavian vein puncture were considered for the new technique. In an
      appropriate postero-anterior (P-A) caudal projection such that the middle part of
      the first rib lay outside the second rib concavity, the needle was inserted into
      the body medial to the coracoid process and advanced dorsally and medially
      towards an imaginary target cranial and lateral to the middle part of the first
      rib. Once the needle tip had reached the imaginary target, it was moved ventro
      dorsally while staying stationary in the fluoroscopic image until venous blood
      was aspirated. RESULT: Navigation by parallax was successful in 21/24 cases (88%)
      and 42/45 separate venous punctures (93%) with an imaginary target, and in the
      remaining three cases with a real guide wire target. There were four
      insignificant axillary arterial punctures. CONCLUSIONS: Navigation by parallax
      with an imaginary or a real target is effective, easy, and simple, and should
      facilitate axillary/subclavian vein puncture in multiple clinical scenarios.

PMID- 18070311
TI  - A misleading long RP tachycardia: what is the mechanism?

PMID- 18070312
TI  - Psychological intervention following implantation of an implantable
      defibrillator: a review and future recommendations.
AB  - BACKGROUND: The medical benefits of the implantable cardioverter defibrillator
      (ICD) are unequivocal, but a subgroup of patients experiences emotional
      difficulties following implantation. For this subgroup, some form of
      psychological intervention may be warranted. This review provides an overview of
      current evidence on the efficacy of psychological intervention in ICD patients
      and recommendations for future research. METHODS: We searched the PubMed and
      PsycInfo databases in the period between January 1980 and April 2007, using a set
      of a priori determined keywords. Based on the search and a hand search of the
      reference lists of the included articles, we identified nine studies that
      fulfilled the inclusion criteria. RESULTS: The majority of studies used a
      randomized controlled trial design, but studies varied considerably in sample
      size, response, attrition rate, and type of intervention. However, most
      interventions were multifactorial, using cognitive behavioral therapy as one of
      the mainstays of treatment. Overall, psychological interventions seem to have
      little impact on shocks and heart rate variability. Some studies found a decrease
      in depressive symptoms and gains in quality of life, but the most notable effects
      are seen in improved exercise capacity and reductions in anxiety. Effect sizes
      for changes in anxiety in the intervention group ranged from small to large
      compared to small in the usual care group, using Cohen's effect size index.
      CONCLUSIONS: Preliminary evidence from small-scale intervention trials suggests
      that psychological intervention is worthwhile in ICD patients. Nevertheless,
      large-scale, well-designed trials are warranted to substantiate these findings. A
      multifactorial approach using a cognitive behavioral component paired with
      exercise training is likely to be the most successful.

PMID- 18070313
TI  - Pseudo crosstalk behavior in a patient with atrio-ventricular block and implanted
      biventricular defibrillator.
AB  - We present a 59-year-old man with a dilated cardiomyopathy (ejection fraction =
      20%), congestive heart failure and atrio-ventricular (AV) block who underwent
      implantation of a biventricular defibrillator (BiV ICD). While undergoing cardiac
      transplant evaluation for drug-refractory ventricular fibrillation, his telemetry
      recorded findings resembling crosstalk inhibition. Device interrogation was
      normal. All episodes occurred at 1:00 a.m. suggesting a routine device operation.
      Left ventricular capture management, a new feature that automatically measures
      left ventricular pacing thresholds at 1:00 a.m., had been programmed to Monitor.
      Understanding this sophisticated pacing algorithm might avoid confusion when
      operative in patients with AV block.

PMID- 18070314
TI  - Retrieval of pacemaker lead tip embolized into the distal pulmonary arterial bed
      during extraction procedure.
AB  - A patient required lead extraction of a dual chamber implantable cardioverter
      defibrillator system for a chronic pocket infection. Using a right subclavian
      approach, the right ventricular leads were removed by dilation/counter traction.
      During the procedure, the tip of the atrial lead was cut and, while the body of
      the lead was extracted, the tip embolized into a distal branch of the right
      pulmonary artery. Despite its distal location, we were able to extract the lead
      tip by an Amplatz goose neck snare kit for intravascular foreign body retrieval,
      commonly used by interventional radiologists, in cooperation with our radiology
      staff.

PMID- 18070315
TI  - Needle directed re-entry to cross a subclavian occlusion following failed
      microdissection.
AB  - Patients with existing internal cardioverter defibrillators (ICDs) often require
      upgrading to a biventricular ICD for treatment of congestive heart failure.
      Placement of a left ventricular (LV) lead can be technically challenging in the
      best of circumstances. A subclavian vein stenosis or occlusion related to
      previously placed leads adds a major obstacle to a successful implant. We report
      a technique to implant an LV lead from the same side as the existing ICD system
      despite failed microdissection of a complete occlusion of the subclavian vein.

PMID- 18070316
TI  - Systemic sarcoidosis revealed by ventricular tachycardia: electrocardiography and
      MRI correspondence.
AB  - We describe a case presenting with ventricular tachycardia as the manifestation
      leading to the diagnosis of sarcoidosis. The ventricular tachyacardia's origin is
      correlated with granuloma localization on magnetic resonance imaging.

PMID- 18070317
TI  - IntraCameral right coronary artery: detection by 64 slice coronary computed
      tomographic angiography and implications for radiofrequency ablation of atrial
      dysrhythmias.
AB  - An intracameral or intracavitary course for a coronary artery is a rare anomaly.
      Nevertheless, it carries a significant impact for invasive cardiac procedures
      that require right atrial catheterization, pacemaker implantation, or
      electrophysiologic study such as radiofrequency ablation. If a coronary artery
      were to be damaged within the atrial chamber by catheter manipulation at the time
      of heart catheterization, serious complications might ensue. We describe the
      first reported case of an intracameral right coronary artery identified with
      multidetector 64-slice coronary computed tomographic angiography performed prior
      to pulmonary venous antral isolation for atrial fibrillation.

PMID- 18070318
TI  - Deglutition induced atrial tachycardia and atrial fibrillation.
AB  - Deglutition induced supraventricular tachycardia is an uncommon condition
      postulated to be a vagally mediated phenomenon due to mechanical stimulation.
      Patients usually present with mild symptoms or may have severe debilitating
      symptoms. Treatment with Class I agents, beta blockers, calcium channel blockers,
      amiodarone and radiofrquency catheter ablation has shown to be successful in the
      majority of reported cases. We report the case of a 46-year-old healthy woman
      presenting with palpitations on swallowing that was documented to be transient
      atrial tachycardia with aberrant ventricular conduction as well as transient
      atrial fibrillation. She was successfully treated with propafenone with no
      induction of swallowing-induced tachycardia after treatment. This is also the
      first case to show swallowing-induced atrial tachycardia and atrial fibrillation
      in the same patient.

PMID- 18070319
TI  - Azithromycin-induced torsade de pointes.
AB  - Although erythromycin frequently induces long QT interval and torsade de pointes,
      the newer drug, azithromycin, has rarely been reported to be associated with
      torsade de pointes. We report here the occurrence of a significant typical QT
      prolongation within a few hours after taking azithromycin which lead to torsade
      de pointes.

PMID- 18070321
TI  - Re: Predicting arrhythmia-free survival using spectral and modified-moving
      average analyses of T-wave alternans.

PMID- 18070323
TI  - In vitro culture of the obligate parasite Spongospora subterranea (cercozoa;
      plasmodiophorida) associated with root-inducing transferred-DNA transformed
      potato hairy roots.
AB  - Spongospora subterranea is a soil-borne, obligate parasitic protist that causes
      powdery scab of potatoes. In this study, an in vitro culture system was developed
      for the maintenance and proliferation of the protist in potato hairy roots. The
      hairy roots of potato were induced in vitro with Agrobacterium rhizogenes.
      Cystosori of S. subterranea from potato scab lesions were surface disinfested and
      used to inoculate potato hairy roots. Plasmodia, zoosporangia, and cystosori were
      observed microscopically in the hairy roots within 6 wk after inoculation,
      indicating the completion of the life cycle of S. subterranea in vitro. This is
      the first in vitro culture system for S. subterranea, and will be a valuable tool
      to study fundamental and practical aspects of the biology of the parasite.

PMID- 18070324
TI  - Taxonomic redescriptions of two ciliates, Protogastrostyla pulchra n. g., n.
      comb. and Hemigastrostyla enigmatica (ciliophora: spirotrichea, stichotrichia),
      with phylogenetic analyses based on 18S and 28S rRNA gene sequences.
AB  - The morphology and infraciliature of two stichotrichid ciliates, Gastrostyla
      pulchra(Perejaslawzewa 1886) Kahl, 1932 and Hemigastrostyla enigmatica(Dragesco
      and Dragesco-Kerneis 1986) Song & Wilbert, 1997, collected from marine and
      brackish sediments, were investigated by using living observations and protargol
      impregnations. Both 18S and 28S rRNA genes of these two species were sequenced.
      The 18S rDNA show high similarities (98.4%-99.7%) among populations of each
      species. There is about 94% similarity in 18S rDNA genes between G. pulchra and
      Gastrostyla steinii, the type species of the genus, which has been confirmed to
      be an oxytrichid by previous studies. In the phylogenetic trees of 18S, 28S, and
      combined 18S and 28S rDNA, both G. pulchra and H. enigmatica are consistently
      placed outside the well-established oxytrichid clade. Based on our analyses and
      previous ontogenetic data, we conclude that these two species may represent some
      lower groups in the subclass Stichotrichia, and that G. pulchra should represent
      a new genus, Protogastrostyla n. g. This new genus, which is morphologically
      similar to Gastrostyla, differs in its morphogenesis: the apical part of the old
      AZM is retained combining with the newly built membranelles that develop from the
      proter's oral primordium; the primary primordia of the dorsal kinety; and
      marginal primordia commence de novo without a definite contribution from the old
      structure.

PMID- 18070325
TI  - An improved method for the analysis of Cryptosporidium parvum oocysts by matrix
      assisted laser desorption/ionization time of flight mass spectrometry.
AB  - Cryptosporidium parvum oocysts were analyzed using matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). Sample
      preparation proved to be a crucial step in the acquisition of acceptable mass
      spectra. Oocysts of C. parvum and the matrix were mixed and held for at least 45
      min to produce reproducible, representative mass spectra. Sporozoites were also
      excysted from oocysts, purified, and analyzed using MALDI-TOF MS. The mass
      spectra of the intact oocysts contained many of the same peaks found in the mass
      spectra of the sporozoites, suggesting that during analysis, the internal
      constituents, not just the oocyst wall, are ablated by the laser.

PMID- 18070326
TI  - Balanion masanensis n. sp. (ciliophora: prostomatea) from the coastal waters of
      Korea: morphology and small subunit ribosomal RNA gene sequence.
AB  - The planktonic ciliate Balanion masanensis n. sp. is described from living cells,
      from cells prepared by quantitative protargol staining (QPS), scanning electron
      microscopy (SEM), and transmitted electron microscopy (TEM) preparations, and the
      sequence of its nuclear small subunit rDNA (SSU rDNA) is reported. This species
      is almost ovoid with a flattened anterior oral region when the cells are alive
      and stained. The flattened anterior region of a living cell often forms a dome
      with the perimeter receded in a groove, and this region is easily inflated or
      depressed. In SEM photos, a brosse of six to nine monokinetids (or possibly three
      to five dikinetids) was observed inside the circumoral dikinetids. In TEM photos,
      circumoral microtubular ribbons were observed below the oral cilia, which along
      with the oral flaps were 8-16 microm in length. The cytostome is a slight funnel
      like central depression on the flattened anterior end. The morphological
      characteristics of this ciliate are identical to those of the genus Balanion
      (Order Prorodontida). The ranges (and mean+/-standard deviation) of cell length,
      cell width, and oral diameter of living cells (n=23-26) were 27-43 microm (35.2+/
      4.6), 25-32 microm (28.6+/-2.3), and 25-30 microm (27.6+/-1.3), respectively,
      while those of the QPS-stained specimens (n=70) were 23-37 microm (30.6+/-3.5),
      26-35 microm (30.7+/-2.2), and 26-33 microm (29.5+/-1.5), respectively. Forty-six
      to 55 somatic kineties (SKs) were equally spaced around the cell body and
      extended from the oral to near the posterior regions with 24-50 monokinetids per
      kinety. Each kinetid bore a cilium 2.8-7.2 microm long. A caudal cilium (ca 14
      microm long) arose on the posterior end. The single ellipsoid macronucleus is 6.8
      13.4 x 6.8-10.5 microm, accompanied by a single micronucleus (2.0-2.8 x 1.5-2.5
      microm) visible only in QPS specimens. Because, the cell size, the number of SKs,
      and the number of kinetosomes per SK of this ciliate were much greater than those
      of Balanion comatum and Balanion planctonicum, the only two Balanion species so
      far reported, we have established B. masanensis n. sp. When properly aligned, the
      sequence of the SSU rDNA of B. masanensis n. sp. (GenBank Accession No. AM412525)
      was approximately 9% different from that of Coleps hirtus (Colepidae,
      Prorodontida) and 12% different from that of Prorodon teres (Prorodontidae,
      Prorodontida).

PMID- 18070327
TI  - An ultrastructural comparison of the attachment sites between Gregarina steini
      and Cryptosporidium muris.
AB  - Early developmental stages of Gregarina steini Berndt, 1902 from the intestine of
      Tenebrio molitor larvae were studied by transmission electron microscopy. The
      formation and structure of the eugregarine attachment site were compared with
      comparable features found on the feeder organelle of Cryptosporidium muris
      Tyzzer, 1907, from the stomach of experimentally infected rodents. The similarity
      of the attachment strategy between both organisms was revealed. The membrane
      fusion site in G. steini, formed by the trophozoite plasma membrane, host cell
      plasma membrane and a membrane-like structure limiting the cortical zone of the
      epimerite, resembles the Y-shaped membrane junction between the host cell plasma
      membrane, the trophozoite plasma membrane and membrane surrounding the anterior
      vacuole in C. muris. The anterior vacuole of C. muris appears to be the precursor
      of the feeder organelle and its structure is very similar to the epimeritic bud
      and the cortical zone of G. steini trophozoites. In both investigated organisms,
      the apical complex disappears early during cell invasion. The possibility of the
      epicellular location of Cryptosporidium on the surface of host cells is
      discussed.

PMID- 18070328
TI  - Amoeba at attention: phylogenetic affinity of Sappinia pedata.
AB  - The genus Sappinia, a taxon of free-living amoebae with trophozoites that
      typically have two closely appressed nuclei, contains two named species, Sappinia
      pedata, the type species, and S. diploidea. The amoebae of both species are
      essentially identical according to the literature. The two species are
      distinguished by S. pedata having a standing amoeba stage, incorrectly
      interpreted as a cyst, and S. diploidea having sessile, bicellular cysts. Using
      four isolates of S. pedata collected from around the world, we present detailed
      light micrographic illustrations of all stages of its life cycle. We confirm that
      the standing amoeba lacks a cell wall. In two isolates of S. pedata, there are
      bicellular cysts indistinguishable from those of S. diploidea. Using sequence
      data from the nuclear small subunit ribosomal RNA gene, we conclude that S.
      pedata and the published neotype of S. diploidea are congeneric but not
      conspecific. The genus branches within Thecamoebidae. Sequencing of the actin
      gene confirms the inclusion of Sappinia in Thecamoebidae. Resolving the taxonomy
      of Sappinia is gaining importance because it has recently been attributed as an
      opportunistic human pathogen.

PMID- 18070329
TI  - Prevalence of Perkinsus marinus (dermo), Haplosporidium nelsoni (MSX), and QPX in
      bivalves of Delaware's inland bays and quantitative, high-throughput diagnosis of
      dermo by QPCR.
AB  - Restoration of oyster reef habitat in the Inland Bays of Delaware was accompanied
      by an effort to detect and determine relative abundance of the bivalve pathogens
      Perkinsus marinus, Haplosporidium nelsoni, and QPX. Both the oyster Crassostrea
      virginica and the clam Mercenaria mercenaria were sampled from the bays. In
      addition, oysters were deployed at eight sites around the bays as sentinels for
      the three parasites. Perkinsus marinus prevalence was measured with a real-time,
      quantitative polymerase chain reaction (PCR) methodology that enabled high
      throughput detection of as few as 31 copies of the ribosomal non-transcribed
      spacer region in 500 ng oyster DNA. The other pathogens were assayed using PCR
      with species-specific primers. Perkinsus marinus was identified in Indian River
      Bay at moderate prevalence ( approximately 40%) in both an artificial reef and a
      wild oyster population whereas sentinel oysters were PCR-negative after 3-months
      exposure during summer and early fall. Haplosporidium nelsoni was restricted to
      one oyster deployed in Little Assawoman Bay. QPX and P. marinus were not detected
      among wild clams. While oysters in these bays have historically been under the
      greatest threat by MSX, it is apparent that P. marinus currently poses a greater
      threat to recovery of oyster aquaculture in Delaware's Inland Bays.

PMID- 18070330
TI  - Redescription of a poorly known marine ciliate, Leptoamphisiella vermis Gruber,
      1888 n. g., n. comb. (ciliophora, stichotrichia, pseudoamphisiellidae), from the
      Yellow Sea, China.
AB  - Leptoamphisiella vermisGruber, 1888 n. g., n. comb. (basionym Epiclintes
      vermisGruber, 1888) is an extraordinarily large and worm-like marine
      stichotrichous ciliate. Based on a population isolated recently from coastal
      waters of Qingdao, China, the living morphology and infraciliature are
      redescribed and its taxonomic position is defined. Accordingly, a new diagnosis
      for this species is suggested: large, marine Leptoamphisiella with a conspicuous
      layer of pellicular alveoli; 400-1000 microm x 40-70 microm in vivo; body band
      like, highly flexible; about 40 membranelles; always three frontal and two buccal
      cirri; 52-80 transverse cirri (TC) extending to the posterior end of the buccal
      field; 57-79 left midventral and 44-62 right midventral cirri; 62-102 cirri in
      left and 63-91 cirri in right marginal rows (MR); 9-13 dorsal kineties that
      extend the full body length; about 100 macronuclear nodules and 5-13 micronuclei.
      The diagnosis for the new genus is as follows: vermiform Pseudoamphisiellidae
      with strongly contractile body, differentiated frontal, buccal, and highly
      developed TC; two remarkably separated midventral rows; one MR on each side of
      the body; frontoterminal and caudal cirri absent. Leptoamphisiella vermis n.
      comb. is fixed as the type species of the new genus.

PMID- 18070331
TI  - Medicare and Medicaid: conflicting incentives for long-term care.
AB  - The structure of Medicare and Medicaid creates conflicting incentives regarding
      dually eligible beneficiaries without coordinating their care. Both Medicare and
      Medicaid have an interest in limiting their costs, and neither has an incentive
      to take responsibility for the management or quality of care. Examples of
      misaligned incentives are Medicare's cost-sharing rules, cost shifting within
      home health care and nursing homes, and cost shifting across chronic and acute
      care settings. Several policy initiatives--capitation, pay-for-performance, and
      the shift of the dually eligible population's Medicaid costs to the federal
      government--may address these conflicting incentives, but all have strengths and
      weaknesses. With the aging baby boom generation and projected federal and state
      budget shortfalls, this issue will be a continuing focus of policymakers in the
      coming decades.

PMID- 18070332
TI  - Care of the chronically ill at home: an unresolved dilemma in health policy for
      the United States.
AB  - The problems of caring for patients with disabling illnesses who neither get well
      nor die are not new. Such patients have always required assistance at home from
      family, benevolent volunteers, or paid caregivers. Despite two centuries of
      experimentation, however, no agreement exists concerning the balance between the
      public and private resources to be allocated through state funding, private
      insurance, and family contributions for the daily and routine care at home for
      chronically ill persons of all ages. This article examines these issues and the
      unavoidable tensions between fiscal reality and legitimate need. It also uses
      historical and policy analyses to explain why home care has never become the
      cornerstone for caring for the chronically ill.

PMID- 18070333
TI  - Labor market work and home care's unpaid caregivers: a systematic review of labor
      force participation rates, predictors of labor market withdrawal, and hours of
      work.
AB  - As people continue to age and receive complex health care services at home,
      concern has arisen about the availability of family caregivers and their ability
      to combine employment with caregiving. This article evaluates the international
      research on unpaid caregivers and their labor market choices, highlighting three
      conclusions: first, caregivers in general are equally as likely to be in the
      labor force as noncaregivers; second, caregivers are more likely to work fewer
      hours in the labor market than noncaregivers, particularly if their caring
      commitments are heavy; and finally, only those heavily involved in caregiving are
      significantly more likely to withdraw from the labor market than noncaregivers.
      Policy recommendations are targeting greater access to formal care for
      "intensive" caregivers and developing workplace policies for employed caregivers.

PMID- 18070334
TI  - The emergence of clinical practice guidelines.
AB  - Clinical practice guidelines are now ubiquitous. This article describes the
      emergence of such guidelines in a way that differs from the two dominant
      explanations, one focusing on administrative cost-cutting and the other on the
      need to protect collective professional autonomy. Instead, this article argues
      that the spread of guidelines represents a new regulation of medical care
      resulting from a confluence of circumstances that mobilized many different
      groups. Although the regulation of quality has traditionally been based on the
      standardization of professional credentials, since the 1960s it has intensified
      and been supplemented by efforts to standardize the use of medical procedures.
      This shift is related to the spread of standardization within medicine and
      especially in research, public health, and large bureaucratic health care
      organizations.

PMID- 18070336
TI  - CD209 in inflammatory bowel disease: a case-control study in the Spanish
      population.
AB  - BACKGROUND: The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD),
      considered together as Inflammatory Bowel Diseases (IBD), involves environmental
      and genetic factors. Although some genes are already known, the genetics
      underlying these diseases is complex and new candidates are continuously
      emerging. The CD209 gene is located in a region linked previously to IBD and a
      CD209 functional polymorphism (rs4804803) has been associated to other
      inflammatory conditions. Our aim was to study the potential involvement of this
      CD209 variant in IBD susceptibility. METHODS: We performed a case-control study
      with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white
      Spaniards. Samples were typed for the CD209 single nucleotide polymorphism (SNP)
      rs4804803 by TaqMan technology. Frequency comparisons were performed using chi2
      tests. RESULTS: No association between CD209 and UC or CD was observed initially.
      However, stratification of UC patients by HLA-DR3 status, a strong protective
      allele, showed that carriage of the CD209_G allele could increase susceptibility
      in the subgroup of HLA-DR3-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04
      3.02, vs. controls). CONCLUSION: A functional variant in the CD209 gene,
      rs4804803, does not seem to be influencing Crohn's disease susceptibility.
      However, it could be involved in the etiology or pathology of Ulcerative Colitis
      in HLA-DR3-positive individuals but further studies are necessary.

PMID- 18070335
TI  - Knowledge transfer and exchange: review and synthesis of the literature.
AB  - Knowledge transfer and exchange (KTE) is as an interactive process involving the
      interchange of knowledge between research users and researcher producers. Despite
      many strategies for KTE, it is not clear which ones should be used in which
      contexts. This article is a review and synthesis of the KTE literature on health
      care policy. The review examined and summarized KTE's current evidence base for
      KTE. It found that about 20 percent of the studies reported on a real-world
      application of a KTE strategy, and fewer had been formally evaluated. At this
      time there is an inadequate evidence base for doing "evidence-based" KTE for
      health policy decision making. Either KTE must be reconceptualized, or strategies
      must be evaluated more rigorously to produce a richer evidence base for future
      activity.

PMID- 18070337
TI  - Distinguishing low frequency oscillations within the 1/f spectral behaviour of
      electromagnetic brain signals.
AB  - BACKGROUND: It has been acknowledged that the frequency spectrum of measured
      electromagnetic (EM) brain signals shows a decrease in power with increasing
      frequency. This spectral behaviour may lead to difficulty in distinguishing event
      related peaks from ongoing brain activity in the electro- and
      magnetoencephalographic (EEG and MEG) signal spectra. This can become an issue
      especially in the analysis of low frequency oscillations (LFOs) - below 0.5 Hz -
      which are currently being observed in signal recordings linked with specific
      pathologies such as epileptic seizures or attention deficit hyperactivity
      disorder (ADHD), in sleep studies, etc. METHODS: In this work we propose a simple
      method that can be used to compensate for this 1/f trend hence achieving spectral
      normalisation. This method involves filtering the raw measured EM signal through
      a differentiator prior to further data analysis. RESULTS: Applying the proposed
      method to various exemplary datasets including very low frequency EEG recordings,
      epileptic seizure recordings, MEG data and Evoked Response data showed that this
      compensating procedure provides a flat spectral base onto which event related
      peaks can be clearly observed. CONCLUSION: Findings suggest that the proposed
      filter is a useful tool for the analysis of physiological data especially in
      revealing very low frequency peaks which may otherwise be obscured by the 1/f
      spectral activity inherent in EEG/MEG recordings.

PMID- 18070339
TI  - Bridging fundamental RNA biology, retroviral replication, and oncogenesis: Karen
      Beemon wins the 2007 Retrovirology Prize.
AB  - The 2007 M. Jeang Retrovirology Prize has been awarded to Dr. Karen L. Beemon.

PMID- 18070338
TI  - Electrical brain imaging evidences left auditory cortex involvement in speech and
      non-speech discrimination based on temporal features.
AB  - BACKGROUND: Speech perception is based on a variety of spectral and temporal
      acoustic features available in the acoustic signal. Voice-onset time (VOT) is
      considered an important cue that is cardinal for phonetic perception. METHODS: In
      the present study, we recorded and compared scalp auditory evoked potentials
      (AEP) in response to consonant-vowel-syllables (CV) with varying voice-onset
      times (VOT) and non-speech analogues with varying noise-onset-time (NOT). In
      particular, we aimed to investigate the spatio-temporal pattern of acoustic
      feature processing underlying elemental speech perception and relate this
      temporal processing mechanism to specific activations of the auditory cortex.
      RESULTS: Results show that the characteristic AEP waveform in response to
      consonant-vowel-syllables is on a par with those of non-speech sounds with
      analogue temporal characteristics. The amplitude of the N1a and N1b component of
      the auditory evoked potentials significantly correlated with the duration of the
      VOT in CV and likewise, with the duration of the NOT in non-speech
      sounds.Furthermore, current density maps indicate overlapping supratemporal
      networks involved in the perception of both speech and non-speech sounds with a
      bilateral activation pattern during the N1a time window and leftward asymmetry
      during the N1b time window. Elaborate regional statistical analysis of the
      activation over the middle and posterior portion of the supratemporal plane (STP)
      revealed strong left lateralized responses over the middle STP for both the N1a
      and N1b component, and a functional leftward asymmetry over the posterior STP for
      the N1b component. CONCLUSION: The present data demonstrate overlapping spatio
      temporal brain responses during the perception of temporal acoustic cues in both
      speech and non-speech sounds. Source estimation evidences a preponderant role of
      the left middle and posterior auditory cortex in speech and non-speech
      discrimination based on temporal features. Therefore, in congruency with recent
      fMRI studies, we suggest that similar mechanisms underlie the perception of
      linguistically different but acoustically equivalent auditory events on the level
      of basic auditory analysis.

PMID- 18070340
TI  - Survival of bronchiectatic patients with respiratory failure in ICU.
AB  - BACKGROUND: The outcome of patients with bronchiectasis during and after their
      stay in the intensive care unit (ICU) has seldom been reported in the literature.
      Managing these patients in the ICU can be challenging because of the complex
      nature of their disease. This study aims to identify the in-hospital and long
      term outcome of patients with bronchiectasis and respiratory failure (RF) in ICU.
      METHODS: A retrospective study was carried out by studying all bronchiectatic
      patients admitted to the medical ICU for RF over a 10-year period (1995-2004).
      RESULTS: The mean (+/- standard deviation) age of 35 patients was 63.5 +/- 11.7
      years and APACHE score was 22.3 +/- 7.3. The 4-year mortality was 60%. Among the
      variables observed, age > 65 years (hazard ratio (HR): 4.15; 95% confidence
      interval (CI): 3.2-5.1), APACHE II score > 24 (2.6, 95% CI 1.7-3.5), intubation
      (2.81, 95 %CI 1.9-3.7), inotropic support (2.9, 95% CI 2.0-3.7), Home-O2 (4.0,
      95% CI 2.7-5.2) and activity index (4.0, 95% CI 2.8-5.3) were associated with
      diminished survival in univariate analysis by Cox regression. By long rank test,
      survival probabilities were significantly low at these strata. Multivariate
      analysis of Cox proportional hazard model showed that age > 65 years (HR: 5.4,
      95% CI 1.9-15.7); activity index (HR: 4.8, 95% CI 1.4-16.6); and inotropic
      support (HR: 3.8, 95% CI 1.5-10.1) were independently associated with reduced
      survival. CONCLUSION: The decreased survival of ICU patients was associated with
      age > 65 years, activity index (bedridden or wheelchair-bound) and use of
      inotropic support.

PMID- 18070341
TI  - Multicentric myxoid liposarcoma: report of two cases.
AB  - BACKGROUND: Multicentric myxoid liposarcoma is a rather infrequent tumour that
      tends to behave aggressively. CASE PRESENTATION: We herein report two further
      cases of this tumour that have been managed in our Hospital. Both were young men
      with multiple sites of involvement at the moment of diagnosis and both have shown
      a bad prognosis with frequent recurrences after treatment and rapid death in one
      case. CONCLUSION: We comment on the diagnosis of this entity and on the
      therapeutic options available for these patients.

PMID- 18070342
TI  - Association of cytokines with endothelium dependent flow mediated vasodilation
      (FMD) of systemic arteries in patients with non-ischemic cardiomyopathy.
AB  - BACKGROUND: Aim of this study was to elucidate the relation between localised
      inflammatory heart disease and endothelial dysfunction in the peripheral
      circulation, considering circulating cytokines as a potential link. METHODS: In
      38 patients with non-ischemic heart disease, myocardial biopsies were examined
      for myocardial inflammation (immunohistology) and virus persistence (PCR).
      Cytokines (sIL-4, IFN-g, IFN-b, IFN-a, sIL-12p7, TNF-a) were measured by ELISA in
      venous serum. Endothelial function of the radial artery was examined by
      ultrasound, measuring diameter changes in response to reactive hyperemia (FMD),
      compared to glyceroltrinitrate (GTN-MD). Patients with EF < 35% were excluded.
      RESULTS: Age 44 +/- 14 years, 19 male, 19 female, EF 63.5[16]%. FMD 4.38 [4.82]%.
      30 patients had myocardial inflammation (8 not), 23 virus persistence (15 not).
      FMD correlated significantly with sIL-12p7 (p = 0.024, r = -0.365), but not with
      other cytokines. sIL-12p7 levels were significantly higher in patients with
      severely impaired FMD (n = 17), compared with normal FMD (n = 21): 10.70 [10.72]
      vs. 4.33 [7.81] pg/ml (p = 0.002). Endothelium independent vasodilation (GTN-MD
      23.67 [8.21]%) was not impaired. CONCLUSION: Endothelial dysfunction of
      peripheral arteries in patients with non-ischemic cardiomyopathy is associated
      with elevated serum concentrations of sIL-12p7, but not of other cytokines.
      Circulating sIL-12p7 may partly explain, that endothelial dysfunction is not
      restricted to the coronary circulation, but involves systemic arteries.

PMID- 18070343
TI  - Variable sexually dimorphic gene expression in laboratory strains of Drosophila
      melanogaster.
AB  - BACKGROUND: Wild-type laboratory strains of model organisms are typically kept in
      isolation for many years, with the action of genetic drift and selection on
      mutational variation causing lineages to diverge with time. Natural populations
      from which such strains are established, show that gender-specific interactions
      in particular drive many aspects of sequence level and transcriptional level
      variation. Here, our goal was to identify genes that display transcriptional
      variation between laboratory strains of Drosophila melanogaster, and to explore
      evidence of gender-biased interactions underlying that variability. RESULTS:
      Transcriptional variation among the laboratory genotypes studied occurs more
      frequently in males than in females. Qualitative differences are also apparent to
      suggest that genes within particular functional classes disproportionately
      display variation in gene expression. Our analysis indicates that genes with
      reproductive functions are most often divergent between genotypes in both sexes,
      however a large proportion of female variation can also be attributed to genes
      without expression in the ovaries. CONCLUSION: The present study clearly shows
      that transcriptional variation between common laboratory strains of Drosophila
      can differ dramatically due to sexual dimorphism. Much of this variation reflects
      sex-specific challenges associated with divergent physiological trade-offs,
      morphology and regulatory pathways operating within males and females.

PMID- 18070344
TI  - Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury,
      morbidity and mortality after pediatric cardiac surgery: a prospective
      uncontrolled cohort study.
AB  - INTRODUCTION: Acute kidney injury (AKI) is a frequent complication of
      cardiopulmonary bypass (CPB). The lack of early biomarkers has impaired our
      ability to intervene in a timely manner. We previously showed in a small cohort
      of patients that plasma neutrophil gelatinase-associated lipocalin (NGAL),
      measured using a research enzyme-linked immunosorbent assay, is an early
      predictive biomarker of AKI after CPB. In this study we tested whether a point-of
      care NGAL device can predict AKI after CPB in a larger cohort. METHOD: First, in
      a cross-sectional pilot study including 40 plasma samples (NGAL range 60 to 730
      ng/ml) and 12 calibration standards (NGAL range 0 to 1,925 ng/ml), NGAL
      measurements by enzyme-linked immunosorbent assay and by Triage NGAL Device
      (Biosite Inc., San Diego, CA, USA) were highly correlated (r = 0.94). Second, in
      a subsequent prospective uncontrolled cohort study, 120 children undergoing CPB
      were enrolled. Plasma was collected at baseline and at frequent intervals for 24
      hours after CPB, and analyzed for NGAL using the Triage(R) NGAL device. The
      primary outcome was AKI, which was defined as a 50% or greater increase in serum
      creatinine. RESULTS: AKI developed in 45 patients (37%), but the diagnosis using
      serum creatinine was delayed by 2 to 3 days after CPB. In contrast, mean plasma
      NGAL levels increased threefold within 2 hours of CPB and remained significantly
      elevated for the duration of the study. By multivariate analysis, plasma NGAL at
      2 hours after CPB was the most powerful independent predictor of AKI (beta =
      0.004, P < 0.0001). For the 2-hour plasma NGAL measurement, the area under the
      curve was 0.96, sensitivity was 0.84, and specificity was 0.94 for prediction of
      AKI using a cut-off value of 150 ng/ml. The 2 hour postoperative plasma NGAL
      levels strongly correlated with change in creatinine (r = 0.46, P < 0.001),
      duration of AKI (r = 0.57, P < 0.001), and length of hospital stay (r = 0.44, P <
      0.001). The 12-hour plasma NGAL strongly correlated with mortality (r = 0.48, P =
      0.004) and all measures of morbidity mentioned above. CONCLUSION: Accurate
      measurements of plasma NGAL are obtained using the point-of-care Triage(R) NGAL
      device. Plasma NGAL is an early predictive biomarker of AKI, morbidity, and
      mortality after pediatric CPB.

PMID- 18070345
TI  - Self-assembling Fmoc dipeptide hydrogel for in situ 3D cell culturing.
AB  - BACKGROUND: Conventional cell culture studies have been performed on 2D surfaces,
      resulting in flat, extended cell growth. More relevant studies are desired to
      better mimic 3D in vivo tissue growth. Such realistic environments should be the
      aim of any cell growth study, requiring new methods for culturing cells in vitro.
      Cell biology is also tending toward miniaturization for increased efficiency and
      specificity. This paper discusses the application of a self-assembling peptide
      derived hydrogel for use as a 3D cell culture scaffold at the microscale.
      RESULTS: Phenylalanine derivative hydrogel formation was seen to occur in
      multiple dispersion media. Cells were immobilized in situ within microchambers
      designed for cell analysis. Use of the highly biocompatible hydrogel components
      and simplistic procedures significantly reduced the cytotoxic effects seen with
      alternate 3D culture materials and microstructure loading methods. Cells were
      easily immobilized, sustained and removed from microchambers. Differences in
      growth morphology were seen in the cultured cells, owing to the 3-dimentional
      character of the gel structure. Degradation improved the removal of hydrogel from
      the microstructures, permitting reuse of the analysis platforms. CONCLUSION: Self
      assembling diphenylalanine derivative hydrogel provided a method to dramatically
      reduce the typical difficulties of microculture formation. Effective generation
      of patterned 3D cultures will lead to improved cell study results by better
      modeling in vivo growth environments and increasing efficiency and specificity of
      cell studies. Use of simplified growth scaffolds such as peptide-derived hydrogel
      should be seen as highly advantageous and will likely become more commonplace in
      cell culture methodology.

PMID- 18070346
TI  - Tetrahydroisoquinoline derivatives: a new perspective on monoaminergic
      dysfunction in children with ADHD?
AB  - BACKGROUND: The dopamine-derived tetrahydroisoquinolines (TIQ) synthesized
      endogeneously from aldehydes and catecholamines have shown to modulate
      neurotransmission, central metabolism and motor activity. Converging evidence has
      implicated abnormalities of the dopamine metabolism to the pathophysiology of
      Attention-Deficit/Hyperactivity Disorder (ADHD). Therefore, four TIQ derivatives
      involved in central dopamine metabolism (salsolinol, N-methyl-salsolinol,
      norsalsolinol, N-methyl-norsalsolinol) have been analyzed for the first time in
      children and adolescents with ADHD and healthy controls. METHODS: 42 children and
      adolescents with ADHD and 24 controls from three sites participated in this pilot
      study. Free and bound amounts of salsolinol, N-methyl-salsolinol, norsalsolinol,
      N-methyl-norsalsolinol have been analyzed in urine. RESULTS: In the ADHD group,
      free and total amounts of the four TIQ derivatives in urine were significantly
      higher compared to urine levels of healthy controls. For N-methyl-salsolinolfree,
      most of the ADHD patients were identified correctly with a sensitivity of 92.5%
      (specificity 94.4%). CONCLUSION: Urine levels of salsolinol, N-methyl-salsolinol,
      norsalsolinol and N-methyl-norsalsolinol are elevated in children and adolescents
      with ADHD and point to a new perspective on catecholaminergic dysfunction in
      ADHD. However, replication and extension of this pilot study would progress this
      innovative and promising field.

PMID- 18070347
TI  - Reconstruction and flux analysis of coupling between metabolic pathways of
      astrocytes and neurons: application to cerebral hypoxia.
AB  - BACKGROUND: It is a daunting task to identify all the metabolic pathways of brain
      energy metabolism and develop a dynamic simulation environment that will cover a
      time scale ranging from seconds to hours. To simplify this task and make it more
      practicable, we undertook stoichiometric modeling of brain energy metabolism with
      the major aim of including the main interacting pathways in and between
      astrocytes and neurons. MODEL: The constructed model includes central metabolism
      (glycolysis, pentose phosphate pathway, TCA cycle), lipid metabolism, reactive
      oxygen species (ROS) detoxification, amino acid metabolism (synthesis and
      catabolism), the well-known glutamate-glutamine cycle, other coupling reactions
      between astrocytes and neurons, and neurotransmitter metabolism. This is, to our
      knowledge, the most comprehensive attempt at stoichiometric modeling of brain
      metabolism to date in terms of its coverage of a wide range of metabolic
      pathways. We then attempted to model the basal physiological behaviour and
      hypoxic behaviour of the brain cells where astrocytes and neurons are tightly
      coupled. RESULTS: The reconstructed stoichiometric reaction model included 217
      reactions (184 internal, 33 exchange) and 216 metabolites (183 internal, 33
      external) distributed in and between astrocytes and neurons. Flux balance
      analysis (FBA) techniques were applied to the reconstructed model to elucidate
      the underlying cellular principles of neuron-astrocyte coupling. Simulation of
      resting conditions under the constraints of maximization of
      glutamate/glutamine/GABA cycle fluxes between the two cell types with subsequent
      minimization of Euclidean norm of fluxes resulted in a flux distribution in
      accordance with literature-based findings. As a further validation of our model,
      the effect of oxygen deprivation (hypoxia) on fluxes was simulated using an FBA
      derivative approach, known as minimization of metabolic adjustment (MOMA). The
      results show the power of the constructed model to simulate disease behaviour on
      the flux level, and its potential to analyze cellular metabolic behaviour in
      silico. CONCLUSION: The predictive power of the constructed model for the key
      flux distributions, especially central carbon metabolism and glutamate-glutamine
      cycle fluxes, and its application to hypoxia is promising. The resultant
      acceptable predictions strengthen the power of such stoichiometric models in the
      analysis of mammalian cell metabolism.

PMID- 18070348
TI  - Gene expression and biological processes influenced by deletion of Stat3 in
      pulmonary type II epithelial cells.
AB  - BACKGROUND: The signal transducer and activator of transcription 3 (STAT3)
      mediates gene expression in response to numerous growth factors and cytokines,
      playing an important role in many cellular processes. To better understand the
      molecular mechanisms by which Stat3 influences gene expression in the lung, the
      effect of pulmonary epithelial cell specific deletion of Stat3 on genome wide
      mRNA expression profiling was assessed. Differentially expressed genes were
      identified from Affymetrix Murine GeneChips analysis and subjected to gene
      ontology classification, promoter analysis, pathway mapping and literature
      mining. RESULTS: Total of 791 mRNAs were significantly increased and 314 mRNAs
      were decreased in response to the deletion of Stat3Delta/Delta in the lung. STAT
      is the most enriched cis-elements in the promoter regions of those differentially
      expressed genes. Deletion of Stat3 induced genes influencing protein metabolism,
      transport, chemotaxis and apoptosis and decreased the expression of genes
      mediating lipid synthesis and metabolism. Expression of Srebf1 and 2, genes
      encoding key regulators of fatty acid and steroid biosynthesis, was decreased in
      type II cells from the Stat3Delta/Delta mice, consistent with the observation
      that lung surfactant phospholipids content was decreased. Stat3 influenced both
      pro- and anti-apoptotic pathways that determine cell death or survival. Akt, a
      potential transcriptional target of Stat3, was identified as an important
      participant in Stat3 mediated pathways including Jak-Stat signaling, apoptosis,
      Mapk signaling, cholesterol and fatty acid biosynthesis. CONCLUSION: Deletion of
      Stat3 from type II epithelial cells altered the expression of genes regulating
      diverse cellular processes, including cell growth, apoptosis and lipid
      metabolism. Pathway analysis indicates that STAT3 regulates cellular homeostasis
      through a complex regulatory network that likely enhances alveolar epithelial
      cell survival and surfactant/lipid synthesis, necessary for the protection of the
      lung during injury.

PMID- 18070350
TI  - Health for sale: the medicinal plant markets in Trujillo and Chiclayo, Northern
      Peru.
AB  - Traditional methods of healing have been beneficial in many countries with or
      without access to conventional allopathic medicine. In the United States, these
      traditional practices are increasingly being sought after for illnesses that
      cannot be easily treated by allopathic medicine. More and more people are
      becoming interested in the knowledge maintained by traditional healers and in the
      diversity of medicinal plants that flourish in areas like Northern Peru. While
      scientific studies of medicinal plants are underway, concern has arisen over the
      preservation of both the large diversity of medicinal plants and the traditional
      knowledge of healing methods that accompanies them. To promote further
      conservation work, this study attempted to document the sources of the most
      popular and rarest medicinal plants sold in the markets of Trujillo (Mayorista
      and Hermelinda) and Chiclayo (Modelo and Moshoqueque), as well as to create an
      inventory of the plants sold in these markets, which will serve as a basis for
      comparison with future inventories. Individual markets and market stalls were
      subjected to cluster analysis based on the diversity of the medicinal plants they
      carry. The results show that markets were grouped based on the presence of: (1)
      common exotic medicinal plants; (2) plants used by laypeople for self-medication
      related to common ailments ("everyday remedies"); (3) specialized medicinal
      plants used by curanderos or traditional healers; and (4) highly "specialized"
      plants used for magical purposes. The plant trade in the study areas seems to
      correspond well with the specific health care demands from clientele in those
      areas. The specific market patterns of plant diversity observed in the present
      study represent a foundation for comparative market research in Peru and
      elsewhere.

PMID- 18070349
TI  - An extensive phenotypic characterization of the hTNFalpha transgenic mice.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNFalpha) is implicated in a wide
      variety of pathological and physiological processes, including chronic
      inflammatory conditions, coronary artery disease, diabetes, obesity, and
      cachexia. Transgenic mice expressing human TNFalpha (hTNFalpha) have previously
      been described as a model for progressive rheumatoid arthritis. In this report,
      we describe extensive characterization of an hTNFalpha transgenic mouse line.
      RESULTS: In addition to arthritis, these hTNFalpha transgenic mice demonstrated
      major alterations in body composition, metabolic rate, leptin levels, response to
      a high-fat diet, bone mineral density and content, impaired fertility and male
      sexual function. Many phenotypes displayed an earlier onset and a higher degree
      of severity in males, pointing towards a significant degree of sexual dimorphism
      in response to deregulated expression of TNFalpha. CONCLUSION: These results
      highlight the potential usefulness of this transgenic model as a resource for
      studying the progressive effects of constitutively expressed low levels of
      circulating TNFalpha, a condition mimicking that observed in a number of human
      pathological conditions.

PMID- 18070351
TI  - The intron 4c allele of the NOS3 gene is associated with ischemic stroke in
      African Americans.
AB  - BACKGROUND: Ischemic stroke is the most common cause of disability in North
      America and in addition to the generally accepted risk factors, there is
      increasing evidence for the potential pathophysiological role of genes. One of
      these genes, the endothelial nitric oxide synthase gene (NOS3) has been reported
      as a genetic risk factor for ischemic stroke. To independently confirm and extend
      the results of these previous reports, we investigated this gene as a risk factor
      for stroke in an ethnically diverse study population. METHODS: Using the TOAST
      classification, we characterized and studied 377 patients with ischemic stroke.
      We genotyped two common variants in the NOS3 gene, the intron 4
      insertion/deletion and an exonic single nucleotide polymorphism (SNP), G894T, in
      these patients and compared them with 502 controls. Chi-square or Fisher's exact
      tests were used to examine allele effects on stroke and stroke subtypes. Logistic
      regression analysis was used to adjust for confounding covariate effects.
      RESULTS: All genotypes are in Hardy-Weinberg equilibrium except for intron 4c,
      which is overrepresented in ischemic stroke patients. In pooled analysis of all
      patients, intron 4c, but not intron 4a, intron 4b or G894T alleles are associated
      with stroke (p < 0.01). In subgroup analysis by race, the intron 4c allele is
      most strongly associated with large artery ischemic stroke in African Americans
      (p < 0.01). CONCLUSION: We are unable to confirm previous reports of an
      association of the intron 4a or the G894T alleles with ischemic stroke. However,
      although limited by a relatively small sample size, our study suggests a
      potentially important role of the intron 4c allele as a genetic marker of
      ischemic stroke in African Americans.

PMID- 18070352
TI  - Rapid, widespread transduction of the murine myocardium using self-complementary
      Adeno-associated virus.
AB  - Adeno-associated virus (AAV) has shown great promise as a gene transfer vector.
      However, the incubation time needed to attain significant levels of gene
      expression is often too long for some clinical applications. Self-complementary
      AAV (scAAV) enters the cell as double stranded DNA, eliminating the step of
      second-strand synthesis, proven to be the rate-limiting step for gene expression
      of single-stranded AAV (ssAAV). The aim of this study was to compare the
      efficiency of these two types of AAV vectors in the murine myocardium. Four day
      old CD-1 mice were injected with either of the two AAV constructs, both
      expressing GFP and packaged into the AAV1 capsid. The animals were held for 4, 6,
      11 or 21 days, after which they were euthanized and their hearts were excised.
      Serial sections of the myocardial tissue were used for real-time PCR
      quantification of AAV genome copies and for confocal microscopy. Although we
      observed similar numbers of AAV genomes at each of the different time points
      present in both the scAAV and the ssAAV infected hearts, microscopic analysis
      showed expression of GFP as early as 4 days in animals injected with the scAAV,
      while little or no expression was observed with the ssAAV constructs until day
      11. AAV transduction of murine myocardium is therefore significantly enhanced
      using scAAV constructs.

PMID- 18070353
TI  - Physicians' migration in Europe: an overview of the current situation.
AB  - BACKGROUND: The migration of medical professionals as a result of the expansion
      of the European Union is cause for concern. But there is a significant lack of
      information available about this phenomenon. METHODS: Search of secondary
      databases about the presence of european doctors working abroad, through two
      search engines in the Internet (Google and Pubmed) and a survey of professional
      organisations and regulators in countries of the European Union. RESULTS: The
      United Kingdom has more foreign doctors than all other European countries for
      which figures are available (Ireland, France, Germany, Norway, Portugal, Italy,
      Austria and Poland). Some 74,031 foreign doctors are registered in the UK, 30.94%
      of the total. European countries with the highest percentage of doctors working
      abroad are Ireland (47.5%, or 10,065 doctors) and Malta (23.1%, 376 doctors). The
      data obtained from Norway, France and Germany do not indicate an increase in the
      migration of professionals from countries recently incorporated into the EU.
      CONCLUSION: There is significant mobility and heterogeneous distribution of
      doctors within the EEA and it should be cause for concern among health care
      authorities. However, there is no evidence about a possible increase in this
      phenomenon after the recent expansion of the EU.

PMID- 18070354
TI  - Trends in influenza vaccination coverage rates in Germany over five seasons from
      2001 to 2006.
AB  - BACKGROUND: To assess influenza vaccination coverage from 2001 to 2006 in
      Germany, to understand drivers and barriers to vaccination and to identify
      vaccination intentions for season 2006/07. METHODS: 9,990 telephone-based
      household surveys from age 14 were conducted between 2001 and 2006. Essentially,
      the same questionnaire was used in all seasons. RESULTS: The influenza
      vaccination coverage rate reached 32.5% in 2005/06. In the elderly (> or years),
      the vaccination rate reached 58.9% in 2005/06. In those aged 65 years and older,
      it was 63.4%. Perceiving influenza as a serious illness was the most frequent
      reason for getting vaccinated. Thirteen percent of those vaccinated in 2005/06
      indicated the threat of avian flu as a reason. The main reason for not getting
      vaccinated was thinking about it without putting it into practice. The major
      encouraging factor to vaccination was a recommendation by the family doctor.
      49.6% of the respondents intend to get vaccinated against influenza in season
      2006/07. CONCLUSION: Increasing vaccination rates were observed from 2001 to 2006
      in Germany. The threat of avian influenza and the extended reimbursement programs
      may have contributed to the recent increase.

PMID- 18070355
TI  - Horizontal gene transfer and nucleotide compositional anomaly in large DNA
      viruses.
AB  - BACKGROUND: DNA viruses have a wide range of genome sizes (5 kb up to 1.2 Mb,
      compared to 0.16 Mb to 1.5 Mb for obligate parasitic bacteria) that do not
      correlate with their virulence or the taxonomic distribution of their hosts. The
      reasons for such large variation are unclear. According to the traditional view
      of viruses as gifted "gene pickpockets", large viral genome sizes could originate
      from numerous gene acquisitions from their hosts. We investigated this hypothesis
      by studying 67 large DNA viruses with genome sizes larger than 150 kb, including
      the recently characterized giant mimivirus. Given that horizontally transferred
      DNA often have anomalous nucleotide compositions differing from the rest of the
      genome, we conducted a detailed analysis of the inter- and intra-genome
      compositional properties of these viruses. We then interpreted their
      compositional heterogeneity in terms of possible causes, including strand
      asymmetry, gene function/expression, and horizontal transfer. RESULTS: We first
      show that the global nucleotide composition and nucleotide word usage of viral
      genomes are species-specific and distinct from those of their hosts. Next, we
      identified compositionally anomalous (cA) genes in viral genomes, using a method
      based on Bayesian inference. The proportion of cA genes is highly variable across
      viruses and does not exhibit a significant correlation with genome size. The vast
      majority of the cA genes were of unknown function, lacking homologs in the
      databases. For genes with known homologs, we found a substantial enrichment of cA
      genes in specific functional classes for some of the viruses. No significant
      association was found between cA genes and compositional strand asymmetry. A
      possible exogenous origin for a small fraction of the cA genes could be confirmed
      by phylogenetic reconstruction. CONCLUSION: At odds with the traditional dogma,
      our results argue against frequent genetic transfers to large DNA viruses from
      their modern hosts. The large genome sizes of these viruses are not simply
      explained by an increased propensity to acquire foreign genes. This study also
      confirms that the anomalous nucleotide compositions of the cA genes is sometimes
      linked to particular biological functions or expression patterns, possibly
      leading to an overestimation of recent horizontal gene transfers.

PMID- 18070356
TI  - High-throughput sequence alignment using Graphics Processing Units.
AB  - BACKGROUND: The recent availability of new, less expensive high-throughput DNA
      sequencing technologies has yielded a dramatic increase in the volume of sequence
      data that must be analyzed. These data are being generated for several purposes,
      including genotyping, genome resequencing, metagenomics, and de novo genome
      assembly projects. Sequence alignment programs such as MUMmer have proven
      essential for analysis of these data, but researchers will need ever faster, high
      throughput alignment tools running on inexpensive hardware to keep up with new
      sequence technologies. RESULTS: This paper describes MUMmerGPU, an open-source
      high-throughput parallel pairwise local sequence alignment program that runs on
      commodity Graphics Processing Units (GPUs) in common workstations. MUMmerGPU uses
      the new Compute Unified Device Architecture (CUDA) from nVidia to align multiple
      query sequences against a single reference sequence stored as a suffix tree. By
      processing the queries in parallel on the highly parallel graphics card,
      MUMmerGPU achieves more than a 10-fold speedup over a serial CPU version of the
      sequence alignment kernel, and outperforms the exact alignment component of
      MUMmer on a high end CPU by 3.5-fold in total application time when aligning
      reads from recent sequencing projects using Solexa/Illumina, 454, and Sanger
      sequencing technologies. CONCLUSION: MUMmerGPU is a low cost, ultra-fast sequence
      alignment program designed to handle the increasing volume of data produced by
      new, high-throughput sequencing technologies. MUMmerGPU demonstrates that even
      memory-intensive applications can run significantly faster on the relatively low
      cost GPU than on the CPU.

PMID- 18070357
TI  - Glutathionylation of beta-actin via a cysteinyl sulfenic acid intermediary.
AB  - BACKGROUND: Cysteinyl residues in actin are glutathionylated, ie. form a mixed
      disulfide with glutathione, even in the absence of exogenous oxidative stress.
      Glutathionylation inhibits actin polymerization and reversible actin
      glutathionylation is a redox dependent mechanism for regulation of the
      cytoskeleton structure. The molecular mechanism that mediates actin
      glutathionylation in vivo is unclear. RESULTS: We have studied glutathionylation
      of alpha- and beta-actin in vitro using an enzyme-linked immunosorbant assay with
      a monoclonal anti-glutathione antibody. alpha- and beta-actin were both
      glutathionylated when incubated with reduced glutathione (GSH) combined with
      diamide as a thiol oxidant. However, beta-actin was also glutathionylated by both
      glutathione disulfide (GSSG) and GSH in the absence of diamide whereas alpha
      actin was poorly glutathionylated by GSH or GSSG. Glutathionylation of beta-actin
      by GSSG is likely to be mediated by a thiol-exchange mechanism whereas
      glutathionylation by GSH requires thiol oxidation. beta-actin glutathionylation
      by GSH was inhibited by arsenite and dimedone suggesting that the mechanism
      involved formation of a cysteinyl sulfenic acid residue in beta-actin.
      CONCLUSION: We conclude that glutathionylation of beta-actin may occur via
      spontaneous oxidation of a cysteinyl residue to a sulfenic acid that readily
      reacts with GSH to form a mixed disulfide. We also show that the reactivity and
      oxidation to a reactive protein thiol intermediary differ between different actin
      isoforms.

PMID- 18070358
TI  - GADD153 expression does not necessarily correlate with changes in culture
      behavior of hybridoma cells.
AB  - BACKGROUND: The acute sensitivity of some hybridoma cell lines to culture-related
      stresses severely limits their productivity. Recent developments in the
      characterization of the stress signals modulating the cellular phenotype revealed
      that the pro-apoptotic transcription factor Gadd153 could be used as a marker to
      facilitate the optimization of mammalian cell cultures. In this report, we
      analyzed the expression of Gadd153 in Sp2/0-Ag14 murine hybridoma cells grown in
      stationary batch culture and subjected to two different culture optimization
      paradigms: L-glutamine supplementation and ectopic expression of Bcl-xL, an anti
      apoptotic gene. RESULTS: The expression of Gadd153 was found to increase in Sp2/0
      Ag14 cells in a manner which coincided with the decline in cell viability. L
      glutamine supplementation prolonged Sp2/0-Ag14 cell survival and greatly
      suppressed Gadd153 expression both at the mRNA and protein level. However,
      Gadd153 levels remained low after L-glutamine supplementation even as cell
      viability declined. Bcl-xL overexpression also extended Sp2/0-Ag14 cell
      viability, initially delayed the induction of Gadd153, but did not prevent the
      increase in Gadd153 protein levels during the later phase of the culture, when
      cell viability was declining. Interestingly, L-glutamine supplementation
      prevented Gadd153 up-regulation in cells ectopically expressing Bcl-xL, but had
      no effect on cell viability. CONCLUSION: This study highlights important
      limitations to the use of Gadd153 as an indicator of cell stress in hybridoma
      cells.

PMID- 18070359
TI  - An epigenetic vaccine model active in the prevention and treatment of melanoma.
AB  - BACKGROUND: Numerous immune genes are epigenetically silenced in tumor cells and
      agents such as histone deacetylase inhibitors (HDACi), which reverse these
      effects, could potentially be used to develop therapeutic vaccines. The
      conversion of cancer cells to antigen presenting cells (APCs) by HDACi treatment
      could potentially provide an additional pathway, together with cross-presentation
      of tumor antigens by host APCs, to establish tumor immunity. METHODS: HDACi
      treated B16 melanoma cells were used in a murine vaccine model, lymphocyte subset
      depletion, ELISpot and Cytotoxicity assays were employed to evaluate immunity.
      Antigen presentation assays, vaccination with isolated apoptotic preparations and
      tumorigenesis in MHC-deficient mice and radiation chimeras were performed to
      elucidate the mechanisms of vaccine-induced immunity. RESULTS: HDACi treatment
      enhanced the expression of MHC class II, CD40 and B7-1/2 on B16 cells and
      vaccination with HDACi-treated melanoma cells elicited tumor specific immunity in
      both prevention and treatment models. Cytotoxic and IFN-gamma-producing cells
      were identified in splenocytes and CD4+, CD8+ T cells and NK cells were all
      involved in the induction of immunity. Apoptotic cells derived from HDACi
      treatments, but not H2O2, significantly enhanced the effectiveness of the
      vaccine. HDACi-treated B16 cells become APCs in vitro and studies in chimeras
      defective in cross presentation demonstrate direct presentation in vivo and short
      term but not memory responses and long-term immunity. CONCLUSION: The efficacy of
      this vaccine derives mainly from cross-presentation which is enhanced by HDACi
      induced apoptosis. Additionally, epigenetic activation of immune genes may
      contribute to direct antigen presentation by tumor cells. Epigenetically altered
      cancer cells should be further explored as a vaccine strategy.

PMID- 18070360
TI  - Validation of a method for identifying nursing home admissions using
      administrative claims.
AB  - BACKGROUND: Currently there is no standard algorithm to identify whether a
      subject is residing in a nursing home from administrative claims. Our objective
      was to develop and validate an algorithm that identifies nursing home admissions
      at the resident-month level using the MarketScan Medicare Supplemental and
      Coordination of Benefit (COB) database. METHODS: The computer algorithms for
      identifying nursing home admissions were created by using provider type, place of
      service, and procedure codes from the 2000 - 2002 MarketScan Medicare COB
      database. After the algorithms were reviewed and refined, they were compared with
      a detailed claims review by an expert reviewer. A random sample of 150 subjects
      from the claims was selected and used for the validity analysis of the
      algorithms. Contingency table analysis, comparison of mean differences,
      correlations, and t-test analyses were performed. Percentage agreement,
      sensitivity, specificity, and Kappa statistics were analyzed. RESULTS: The
      computer algorithm showed strong agreement with the expert review (99.9%) for
      identification of the first month of nursing home residence, with high
      sensitivity (96.7%), specificity (100%) and a Kappa statistic of 0.97. Weighted
      Pearson correlation coefficient between the algorithm and the expert review was
      0.97 (p < 0.0001). CONCLUSION: A reliable algorithm indicating evidence of
      nursing home admission was developed and validated from administrative claims
      data. Our algorithm can be a useful tool to identify patient transitions from and
      to nursing homes, as well as to screen and monitor for factors associated with
      nursing home admission and nursing home discharge.

PMID- 18070361
TI  - Amyloid precursor protein modulates beta-catenin degradation.
AB  - BACKGROUND: The amyloid precursor protein (APP) is genetically associated with
      Alzheimer's disease (AD). Elucidating the function of APP should help understand
      AD pathogenesis and provide insights into therapeutic designs against this
      devastating neurodegenerative disease. RESULTS: We demonstrate that APP
      expression in primary neurons induces beta-catenin phosphorylation at Ser33,
      Ser37, and Thr41 (S33/37/T41) residues, which is a prerequisite for beta-catenin
      ubiquitinylation and proteasomal degradation. APP-induced phosphorylation of beta
      catenin resulted in the reduction of total beta-catenin levels, suggesting that
      APP expression promotes beta-catenin degradation. In contrast, treatment of
      neurons with APP siRNAs increased total beta-catenin levels and decreased beta
      catenin phosphorylation at residues S33/37/T41. Further, beta-catenin was
      dramatically increased in hippocampal CA1 pyramidal cells from APP knockout
      animals. Acute expression of wild type APP or of familial AD APP mutants in
      primary neurons downregulated beta-catenin in membrane and cytosolic fractions,
      and did not appear to affect nuclear beta-catenin or beta-catenin-dependent
      transcription. Conversely, in APP knockout CA1 pyramidal cells, accumulation of
      beta-catenin was associated with the upregulation of cyclin D1, a downstream
      target of beta-catenin signaling. Together, these data establish that APP
      downregulates beta-catenin and suggest a role for APP in sustaining neuronal
      function by preventing cell cycle reactivation and maintaining synaptic
      integrity. CONCLUSION: We have provided strong evidence that APP modulates beta
      catenin degradation in vitro and in vivo. Future studies may investigate whether
      APP processing is necessary for beta-catenin downregulation, and determine if
      excessive APP expression contributes to AD pathogenesis through abnormal beta
      catenin downregulation.

PMID- 18070363
TI  - Bio F1B hamster: a unique animal model with reduced lipoprotein lipase activity
      to investigate nutrient mediated regulation of lipoprotein metabolism.
AB  - BACKGROUND: Bio F1B hamster is an inbred hybrid strain that is highly susceptible
      to diet-induced atherosclerosis. We previously reported that feeding a high fat
      fish oil diet to Bio F1B hamster caused severe hyperlipidaemia. In this study we
      compared the effects of various diets in the Bio F1B hamster and the Golden
      Syrian hamster, which is an outbred hamster strain to investigate whether genetic
      background plays an important role in dietary fat mediated regulation of
      lipoprotein metabolism. We further investigated the mechanisms behind diet
      induced hyperlipidaemia in F1B hamster. METHODS: The Bio F1B and Golden Syrian
      hamsters, 8 weeks old, were fed high fat diets rich in either monounsaturated
      fatty acids, an n-6: n-3 ratio of 5 or a fish oil diet for 4 weeks. Animals were
      fasted overnight and blood and tissue samples were collected. Plasma was
      fractionated into various lipoprotein fractions and assayed for triacylglycerol
      and cholesterol concentrations. Plasma lipoprotein lipase activity was measured
      using radioisotope method. Microsomal triglyceride transfer protein activity was
      measured in the liver and intestine. Plasma apolipoproteinB48, -B100 and
      apolipoprotein E was measured using Western blots. Two-way ANOVA was used to
      determine the effect of diet type and animal strain. RESULTS: The fish oil fed
      F1B hamsters showed milky plasma after a 14-hour fast. Fish oil feeding caused
      accumulation of apolipoproteinB48 containing lipoprotein particles suggesting
      hindrance of triglyceride-rich lipoprotein clearance. There was no significant
      effect of diet or strain on hepatic or intestinal microsomal triglyceride
      transfer protein activity indicating that hyperlipidaemia is not due to an
      increase in the assembly or secretion of lipoprotein particles. F1B hamsters
      showed significantly reduced levels of lipoprotein lipase activity, which was
      inhibited by fish oil feeding. CONCLUSION: Evidence is presented for the first
      time that alterations in lipoprotein lipase activity and mRNA levels contribute
      to varied response of these hamsters to dietary fat, highlighting the importance
      of genetic background in the regulation of lipid and lipoprotein metabolism by
      dietary fats. Bio F1B hamster may prove to be an important animal model to
      investigate nutrient mediated regulation of metabolic parameters under
      lipoprotein lipase deficiency.

PMID- 18070362
TI  - Estimating past hepatitis C infection risk from reported risk factor histories:
      implications for imputing age of infection and modeling fibrosis progression.
AB  - BACKGROUND: Chronic hepatitis C virus infection is prevalent and often causes
      hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver
      failure. Study of fibrosis progression often relies on imputing the time of
      infection, often as the reported age of first injection drug use. We sought to
      examine the accuracy of such imputation and implications for modeling factors
      that influence progression rates. METHODS: We analyzed cross-sectional data on
      hepatitis C antibody status and reported risk factor histories from two large
      studies, the Women's Interagency HIV Study and the Urban Health Study, using
      modern survival analysis methods for current status data to model past infection
      risk year by year. We compared fitted distributions of past infection risk to
      reported age of first injection drug use. RESULTS: Although injection drug use
      appeared to be a very strong risk factor, models for both studies showed that
      many subjects had considerable probability of having been infected substantially
      before or after their reported age of first injection drug use. Persons reporting
      younger age of first injection drug use were more likely to have been infected
      after, and persons reporting older age of first injection drug use were more
      likely to have been infected before. CONCLUSION: In cross-sectional studies of
      fibrosis progression where date of HCV infection is estimated from risk factor
      histories, modern methods such as multiple imputation should be used to account
      for the substantial uncertainty about when infection occurred. The models
      presented here can provide the inputs needed by such methods. Using reported age
      of first injection drug use as the time of infection in studies of fibrosis
      progression is likely to produce a spuriously strong association of younger age
      of infection with slower rate of progression.

PMID- 18070364
TI  - Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal
      ovarian surface epithelial cells treated with progesterone: implications for
      pathogenesis of ovarian cancer.
AB  - BACKGROUND: Ovarian cancer (OvCa) most often derives from ovarian surface
      epithelial (OSE) cells. Several lines of evidence strongly suggest that increased
      exposure to progesterone (P4) protects women against developing OvCa. However,
      the underlying mechanisms of this protection are incompletely understood.
      METHODS: To determine downstream gene targets of P4, we established short term in
      vitro cultures of non-neoplastic OSE cells from six subjects, exposed the cells
      to P4 (10-6 M) for five days and performed transcriptional profiling with
      oligonucleotide microarrays containing over 22,000 transcripts. RESULTS: We
      identified concordant but modest gene expression changes in cholesterol/lipid
      homeostasis genes in three of six samples (responders), whereas the other three
      samples (non-responders) showed no expressional response to P4. The most up
      regulated gene was TMEM97 which encodes a transmembrane protein of unknown
      function (MAC30). Analyses of outlier transcripts, whose expression levels
      changed most significantly upon P4 exposure, uncovered coordinate up-regulation
      of 14 cholesterol biosynthesis enzymes, insulin-induced gene 1, low density
      lipoprotein receptor, ABCG1, endothelial lipase, stearoyl- CoA and fatty acid
      desaturases, long-chain fatty-acyl elongase, and down-regulation of steroidogenic
      acute regulatory protein and ABCC6. Highly correlated tissue-specific expression
      patterns of TMEM97 and the cholesterol biosynthesis genes were confirmed by
      analysis of the GNF Atlas 2 universal gene expression database. Real-time
      quantitative RT-PCR analyses revealed 2.4-fold suppression of the TMEM97 gene
      expression in short-term cultures of OvCa relative to the normal OSE cells.
      CONCLUSION: These findings suggest that a co-regulated transcript network of
      cholesterol/lipid homeostasis genes and TMEM97 are downstream targets of P4 in
      normal OSE cells and that TMEM97 plays a role in cholesterol and lipid
      metabolism. The P4-induced alterations in cholesterol and lipid metabolism in OSE
      cells might play a role in conferring protection against OvCa.

PMID- 18070365
TI  - A nanoplex PCR assay for the rapid detection of vancomycin and bifunctional
      aminoglycoside resistance genes in Enterococcus species.
AB  - BACKGROUND: Enterococci have emerged as a significant cause of nosocomial
      infections in many parts of the world over the last decade. The most common
      enterococci strains present in clinical isolates are E. faecalis and E. faecium
      which have acquired resistant to either gentamicin or vancomycin. The
      conventional culture test takes 2-5 days to yield complete information of the
      organism and its antibiotic sensitivity pattern. Hence our present study was
      focused on developing a nanoplex PCR assay for the rapid detection of vancomycin
      and bifunctional aminoglycoside resistant enterococci (V-BiA-RE). This assay
      simultaneously detects 8 genes namely 16S rRNA of Enterococcus genus, ddl of E.
      faecalis and E. faecium, aacA-aphD that encodes high level gentamicin resistance
      (HLGR), multilevel vancomycin resistant genotypes such as vanA, vanB, vanC and
      vanD and one internal control gene. RESULTS: Unique and specific primer pairs
      were designed to amplify the 8 genes. The specificity of the primers was
      confirmed by DNA sequencing of the nanoplex PCR products and BLAST analysis. The
      sensitivity and specificity of V-BiA-RE nanoplex PCR assay was evaluated against
      the conventional culture method. The analytical sensitivity of the assay was
      found to be 1 ng at the DNA level while the analytical specificity was evaluated
      with 43 reference enterococci and non-enterococcal strains and was found to be
      100%. The diagnostic accuracy was determined using 159 clinical specimens, which
      showed that 97% of the clinical isolates belonged to E. faecalis, of which 26%
      showed the HLGR genotype, but none were vancomycin resistant. The presence of an
      internal control in the V-BiA-RE nanoplex PCR assay helped us to rule out false
      negative cases. CONCLUSION: The nanoplex PCR assay is robust and can give results
      within 4 hours about the 8 genes that are essential for the identification of the
      most common Enterococcus spp. and their antibiotic sensitivity pattern. The PCR
      assay developed in this study can be used as an effective surveillance tool to
      study the prevalence of enterococci and their antibiotic resistance pattern in
      hospitals and farm animals.

PMID- 18070366
TI  - Predicting gene ontology functions from protein's regional surface structures.
AB  - BACKGROUND: Annotation of protein functions is an important task in the post
      genomic era. Most early approaches for this task exploit only the sequence or
      global structure information. However, protein surfaces are believed to be
      crucial to protein functions because they are the main interfaces to facilitate
      biological interactions. Recently, several databases related to structural
      surfaces, such as pockets and cavities, have been constructed with a
      comprehensive library of identified surface structures. For example, CASTp
      provides identification and measurements of surface accessible pockets as well as
      interior inaccessible cavities. RESULTS: A novel method was proposed to predict
      the Gene Ontology (GO) functions of proteins from the pocket similarity network,
      which is constructed according to the structure similarities of pockets. The
      statistics of the networks were presented to explore the relationship between the
      similar pockets and GO functions of proteins. Cross-validation experiments were
      conducted to evaluate the performance of the proposed method. Results and codes
      are available at: http://zhangroup.aporc.org/bioinfo/PSN/. CONCLUSION: The
      computational results demonstrate that the proposed method based on the pocket
      similarity network is effective and efficient for predicting GO functions of
      proteins in terms of both computational complexity and prediction accuracy. The
      proposed method revealed strong relationship between small surface patterns (or
      pockets) and GO functions, which can be further used to identify active sites or
      functional motifs. The high quality performance of the prediction method together
      with the statistics also indicates that pockets play essential roles in
      biological interactions or the GO functions. Moreover, in addition to pockets,
      the proposed network framework can also be used for adopting other protein
      spatial surface patterns to predict the protein functions.

PMID- 18070368
TI  - Worms and germs: the population dynamic consequences of microparasite
      macroparasite co-infection.
AB  - Hosts are typically simultaneously co-infected by a variety of microparasites
      (e.g. viruses and bacteria) and macroparasites (e.g. parasitic helminths).
      However, the population dynamical consequences of such co-infections and the
      implications for the effectiveness of imposed control programmes have yet to be
      fully realised. Mathematical models may provide an important framework for
      exploring such issues and have proved invaluable in helping to understand the
      factors affecting the epidemiology of single parasitic infections. Here the first
      population dynamic model of microparasite-macroparasite co-infection is presented
      and used to explore how co-infection alters the predictions of the existing
      single-species models. It is shown that incorporating an additional parasite
      species into existing models can greatly stabilise them, due to the combined
      density-dependent impacts on the host population, but co-infection can also
      restrict the region of parameter space where each species could persist alone.
      Overall it is concluded that the dynamic feedback between host, microparasite and
      macroparasite means that it is difficult to appreciate the factors affecting
      parasite persistence and predict the effectiveness of control by just studying
      one component in isolation.

PMID- 18070367
TI  - Peripheral Arterial Disease study (PERART): prevalence and predictive values of
      asymptomatic peripheral arterial occlusive disease related to cardiovascular
      morbidity and mortality.
AB  - BACKGROUND: The early diagnosis of atherosclerotic disease is essential for
      developing preventive strategies in populations at high risk and acting when the
      disease is still asymptomatic. A low ankle-arm index (AAI) is a good marker of
      vascular events and may be diminished without presenting symptomatology (silent
      peripheral arterial disease). The aim of the PERART study (PERipheral ARTerial
      disease) is to determine the prevalence of peripheral arterial disease (both
      silent and symptomatic) in a general population of both sexes and determine its
      predictive value related to morbimortality (cohort study). METHODS/DESIGN: This
      cross-over, cohort study consists of 2 phases: firstly a descriptive, transversal
      cross-over study to determine the prevalence of peripheral arterial disease, and
      secondly, a cohort study to evaluate the predictive value of AAI in relation to
      cardiovascular morbimortality. From September 2006 to June 2007, a total of 3,010
      patients over the age of 50 years will be randomly selected from a population
      adscribed to 24 healthcare centres in the province of Barcelona (Spain). The
      diagnostic criteria of peripheral arterial disease will be considered as an AAI <
      0.90, determined by portable Doppler (8 Mhz probe) measured twice by trained
      personnel. Cardiovascular risk will be calculated with the Framingham-Wilson
      tables, with Framingham calibrated by the REGICOR and SCORE groups. The subjects
      included will be evaluted every 6 months by telephone interview and the clnical
      history and death registries will be reviewed. The appearance of the following
      cardiovascular events will be considered as variables of response: transitory
      ischaemic accident, ictus, angina, myocardial infartction, symptomatic abdominal
      aneurysm and vascular mortality. DISCUSSION: In this study we hope to determine
      the prevalence of peripheral arterial disease, especially the silent forms, in
      the general population and establish its relationship with cardiovascular
      morbimortality. A low AAI may be a better marker of arterial disease than the
      classical cardiovascular risk factors and may, therefore, contribute to improving
      the predictive value of the equations of cardiovascular risk and thereby allowing
      optimisation of multifactorial treatment of atherosclerotic disease.

PMID- 18070369
TI  - The prevalence of personality disorder in schizophrenia and psychotic disorders:
      systematic review of rates and explanatory modelling.
AB  - BACKGROUND: Personality disorder (PD) in psychosis is poorly studied. As PD can
      affect outcome in mental disorders, it is important to understand its prevalence
      in order to plan services, understand prognosis more fully and maximize
      management options. MethodLiterature searching revealed 3972 potential papers.
      Twenty papers including 6345 patients were included in the final analysis. There
      was great variation in prevalence and multilevel modelling was used to identify
      possible reasons for this heterogeneity. RESULTS: The prevalence of PD varied
      from 4.5% to 100%. Multilevel analysis suggested country of study, study type,
      the instruments used to diagnose PD and patient care correlated with the
      prevalence data explaining the study level heterogeneity, with 34.2, 33.4, 17.0
      and 4.5% by each variable respectively. Personality studies in Canada and Sweden
      reported lower PD prevalence, whereas in Spain it was higher than the
      multinational study. Compared with randomized controlled trials, case-control
      studies reported lower prevalence [odds ratio (OR)=0.35, 95% confidence interval
      (CI) 0.15-0.79] and observational studies higher prevalence (OR 70.5, 95% CI 8.5
      583). Primary-care patients were less likely to be diagnosed (OR 0.02, 95% CI 0
      0.19) than hospital patients, and out-patients had higher prevalence (OR 12.5,
      95% CI 1.77-88.6). CONCLUSIONS: The reported prevalence of PD in schizophrenia
      varies significantly. Statistical modelling suggests care, country, study type
      and diagnostic tools for PD all bias prevalence rates. The number of papers
      reaching the inclusion criteria, the relative paucity of information and the
      difficulties in developing an accurate statistical model limited interpretation
      from the study.

PMID- 18070370
TI  - From conduct disorder to severe mental illness: a risky pathway.

PMID- 18070371
TI  - Toward an understanding of risk factors for anorexia nervosa: a case-control
      study.
AB  - BACKGROUND: Prospective, longitudinal studies of risk factors for anorexia
      nervosa (AN) are lacking and existing cross-sectional studies are generally
      narrow in focus and lack methodological rigor. Building on two studies that used
      the Oxford Risk Factor Interview (RFI) to establish time precedence and
      comprehensively assess potential risk correlates for AN, the present study
      advances this line of research and represents the first case-control study of
      risk factors for AN in the USA. METHOD: The RFI was used for retrospective
      assessment of a broad range of risk factors, while establishing time precedence.
      Using a case-control design, 50 women who met DSM-IV criteria for AN were
      compared to those with non-eating disorder DSM-IV psychiatric disorders (n=50)
      and those with no psychiatric disorder (n=50). RESULTS: Women with psychiatric
      disorders reported higher rates of negative affectivity, maternal and paternal
      parenting problems, family discord, parental mood and substance disorder, and
      physical and sexual abuse than women with no psychiatric disorder. Women with AN
      specifically reported greater severity and significantly higher rates of negative
      affectivity, perfectionism and family discord, and higher parental demands than
      women with other psychiatric disorders. The role of weight and shape concerns was
      most salient in the year preceding onset of AN. CONCLUSIONS: Convergent data
      identifying common risk factors as well as those more severe in the development
      of AN are emerging to inform longitudinal risk factor and prevention studies for
      this disorder.

PMID- 18070372
TI  - Associations between ethnicity and self-reported hallucinations in a population
      sample of young adults in The Netherlands.
AB  - BACKGROUND: Psychotic disorders are more common in people from ethnic minorities.
      If psychosis exists as a continuous phenotype, ethnic disparities in psychotic
      disorder will be accompanied by similar ethnic disparities in the rate of
      psychotic symptoms. This study examined ethnic disparities in self-reported
      hallucinations in a population sample of young adults. MethodA cross-sectional
      population survey (n=2258) was carried out in the south-west Netherlands. Seven
      ethnic groups were delineated: Dutch natives, Turks, Moroccans,
      Surinamese/Antilleans, Indonesians, other non-Western immigrants (mostly from
      Africa or Asia) and Western immigrants (mostly from Western Europe). Self
      reported auditory and visual hallucinations were assessed with the Adult Self
      Report (ASR). Indicators of social adversity included social difficulties and a
      significant drop in financial resources. RESULTS: Compared to Dutch natives,
      Turkish females [odds ratio (OR) 13.48, 95% confidence interval (CI) 5.97-30.42],
      Moroccan males (OR 8.36, 95% CI 3.29-21.22), Surinamese/Antilleans (OR 2.19, 95%
      CI 1.05-4.58), Indonesians (OR 4.15, 95% CI 1.69-10.19) and other non-Western
      immigrants (OR 3.57, 95% CI 1.62-7.85) were more likely to report hallucinations,
      whereas Western immigrants, Turkish males and Moroccan females did not differ
      from their Dutch counterparts. When adjusting for social adversity, the ORs for
      self-reported hallucinations among the non-Western immigrant groups showed
      considerable reductions of 28% to 52%. CONCLUSIONS: In a general population
      sample, several non-Western immigrant groups reported hallucinations more often
      than Dutch natives, which is consistent with the higher incidence of psychotic
      disorders in most of these groups. The associations between ethnicity and
      hallucinations diminished after adjustment for social adversity, which supports
      the view that adverse social experiences contribute to the higher rate of
      psychosis among migrants.

PMID- 18070373
TI  - Differences in prevalence and patterns of substance use in schizophrenia and
      bipolar disorder.
AB  - BACKGROUND: Schizophrenia and bipolar disorder have partly overlapping clinical
      profiles, which include an over-representation of substance-use behaviour. There
      are few previous studies directly comparing substance-use patterns in the two
      disorders. The objective of the present study was to compare the prevalence of
      substance use in schizophrenia and bipolar disorder, and investigate possible
      differences in pattern and frequency of use. METHOD: A total of 336 patients with
      schizophrenia or bipolar spectrum disorder from a catchment area-based hospital
      service were included in a cross-sectional study. In addition to thorough
      clinical assessments, patients were interviewed about drug-use history, habits
      and patterns of use. The prevalence and drug-use patterns were compared between
      groups. RESULTS: Patients with bipolar disorder had higher rates of alcohol
      consumption, while schizophrenia patients more often used centrally stimulating
      substances, had more frequent use of non-alcoholic drugs and more often used more
      than one non-alcoholic drug. Single use of cannabis was more frequent in bipolar
      disorder. CONCLUSION: The present study showed diagnosis-specific patterns of
      substance use in severe mental disorder. This suggests a need for more disease
      specific treatment strategies, and indicates that substance use may be an
      important factor in studies of overlapping disease mechanisms.

PMID- 18070374
TI  - A novel interpretation of closing volume based on single-breath nitrogen washout
      curve simulation.
AB  - Although closing volume is regarded as a clinical test for the early detection of
      peripheral airway closure, its grounds are not clear. There have been no
      simulation studies for phase IV in the single-breath nitrogen washout (SBNW)
      curve, even though several mathematical models for phase III have been proposed.
      We modeled the lung tissue deformation during slow expiration in which the tissue
      was regarded as a porous elastic body similar to a sponge. We assigned the
      maximum tissue density of lung parenchyma over which the lung tissue could not be
      contracted according to several experimental reports in literature. SBNW curves
      were then simulated by computing expired air volume and nitrogen concentration
      for respective acini in the lung model. The simulated SBNW curves well reproduced
      phase IV, cardiac oscillation, and its postural changes. We found that the higher
      lung compliance increased closing volume, but decreased residual volume. The
      smaller maximum tissue density generated larger closing volume and larger
      residual volume. It suggested that phase IV reflected the alveolar contractility,
      and the increase of closing volume in emphysema could be explained by an
      insufficient contraction of alveoli. We also found that the distribution of
      maximum tissue density affected the onset of Phase IV. A constant value of
      density generated a clear onset, but a wide distribution of it corresponding to
      peripheral airway closure obscured it. We suggest that the airway closure was not
      necessary for phase IV appearance in both normal and emphysematous lung.

PMID- 18070375
TI  - British National Party representations of Muslims in the month after the London
      bombings: homogeneity, threat, and the conspiracy tradition.
AB  - This study presents an analysis of articles written by prominent members of the
      British National Party. Each of these articles discussed Muslims and Islam in the
      aftermath of the 7 July 2005 London bombings. Two prominent discursive themes are
      discussed here. The first concerned the writers' constructions of the threat that
      Muslims and Islam pose to Britain. Central to this theme were constructions of
      Muslims as 'fascists', anti-white racists, and all potentially dangerous,
      although there was variability in this. Using the Koran as evidence, the articles
      present a vision of a faith which intends to take over the country; in this way,
      a homogenous, culturally essentialist version of Muslims is worked up. The second
      theme illustrates how the writers challenge those who believe that creating a
      British multicultural society is possible, and in doing so construct liberals and
      multiculturalists as also posing a threat to the country. The ways in which this
      represents a variety of conspiracy theory, and the implications of these
      constructions for social action, are discussed.

PMID- 18070376
TI  - Acquiescent responding in partially balanced multidimensional scales.
AB  - We propose a method for controlling acquiescent response in which acquiescence
      response variance is isolated in an independent factor. This kind of procedure is
      available for perfectly balanced scales (i.e. half of the items are worded in the
      opposite direction to the other half with respect to a general trait). However,
      few questionnaires are designed so that exactly half of the items are worded in
      this way. If this is not the case, the available methods are useless. We propose
      to adapt the rotation method of Lorenzo-Seva and Rodriguez-Fornells to handle
      partially balanced scales (i.e. only a few items in the scale are worded in the
      opposite direction). The most important characteristic of our method is that it
      removes the variance due to acquiescent response from all the items in the
      questionnaire (i.e. the balanced subset of items, but also the unbalanced subsets
      of items). The usefulness of the method is illustrated in a numerical example.

PMID- 18070377
TI  - How second-grade students internalize rules during teacher-student transactions:
      a case study.
AB  - BACKGROUND: Vygotsky's theory of the internalization of signs provided the basis
      for this study. AIMS: This study tried to analyse the processes by which second
      grade students internalize school rules. SAMPLE: Ethnographic data were collected
      on 102 lessons in a second-grade class (6-8 years) during 1 year. This study
      focused on three lessons (ethnographic data completed by video-recordings, post
      lesson interviews with the teacher, and re-transcriptions of the verbal
      interactions of the lessons and interviews). METHOD: The longitudinal observation
      data were broken down into discrete transactions, crossed with the recorded data,
      and analysed in a four-step procedure. RESULTS: The results showed that the
      students' self-regulated actions (voluntary performance of prescribed actions)
      corresponded to the teacher's presentation of the rules, which was varied and
      personalized. She used explanation/justification, negotiation, persuasion, or
      imposition as a function of the situation and the students concerned. The results
      revealed: (a) Multiple actions of explanation/justification of the rules,
      negotiation and persuasion to the entire class, (b) Personalized actions of
      persuasion and rule imposition in instances of heteronomous actions by students,
      (c) Actions adjusted to the dynamics of the transactions. CONCLUSION: This study
      demonstrates how closely the actions of teacher and students are linked. More
      than a linear process of rules internalization, education looks like a co
      construction of rules between teacher and students. These results can serve as a
      basis for the tools of teacher teaching.

PMID- 18070378
TI  - Intelligence for education: as described by Piaget and measured by psychometrics.
AB  - Two separate paths to the concept of intelligence are discussed: the psychometric
      path being concerned with the measurement of intelligence, involving the
      methodology of norm-referenced testing; the path followed by Piaget, and others,
      addresses from the start the related question of how intelligence can be
      described, and employs a criterion-referenced methodology. The achievements of
      psychometrics are briefly described, with an argument that they now remain
      important tools of what Kuhn called 'normal science'. The criterion-referenced
      approach of Piaget and others is described, with evidence from intervention
      studies that the Genevan descriptions of children-in-action have allowed the
      choice of contexts within which children can profitably be challenged to go
      further in their thinking. Hence, Genevan psychology is also now a part of the
      normal science with important uses, shown both in neo-Piagetian studies and
      further research stemming from Geneva. Discussion of the 'Flynn effect' sheds
      light on both paths, with problems still unresolved. The argument is then
      developed that the relevance of neuroscience needs to be discussed to try to
      decide in what ways it may provide useful insights into intelligence.

PMID- 18070383
TI  - Carbon analysis for inspecting carbonation of concrete using a TEA CO2 laser
      induced plasma.
AB  - It has been demonstrated that a spectrochemical analysis of carbon using the
      laser plasma method can be successfully applied to inspect the carbonation of
      concrete by detecting carbon produced in aged concrete by a chemical reaction of
      Ca(OH)2 with CO2 gas in environmental air, turning into CaCO3, which induces
      degradation of the quality of building concrete. A comparative study has been
      made using a TEA CO2 laser (500-1000 mJ) and a Q-switched Nd-YAG laser (50-200
      mJ) to search for the optimum conditions for carbon analysis, proving the
      advantage of the TEA CO2 laser for this purpose. Also, it was clarified that
      laser irradiation with suitable defocusing conditions is a crucial point for
      obtaining high sensitivity in the detection of carbon. Practical experiments on
      the inspection of carbonation were carried out using both a concrete sample that
      had been intentionally carbonated by exposure to high concentrations of CO2 gas
      and a naturally carbonated concrete sample. As a result, good coincidence was
      observed between the laser method and the ordinary method, which uses the
      chemical indicator phenolphthalein, implying that this laser technique is
      applicable as an in situ quantitative method of inspection for carbonation of
      concrete.

PMID- 18070379
TI  - An international survey of sleeping problems in the general population.
AB  - OBJECTIVE: This international omnibus survey investigated the prevalence and
      characteristics of sleep problems, as well as strategies for resolving sleep
      problems, in the general population of the USA, France, Germany, Italy, Spain,
      the UK and Japan. RESEARCH DESIGN AND METHODS: A representative sample of the
      general population aged > or = 15 years was recruited from each country.
      Questions focused on the nature of sleeping problems, the impact of problems on
      daily functioning and behavior with regard to resolving sleeping problems.
      RESULTS: A total of 10 132 individuals were included in this survey. The
      prevalence of sleeping problems was 56% in the USA, 31% in Western Europe and 23%
      in Japan. Most individuals with sleeping problems considered these to have an
      impact on their daily functioning, with family life most affected in the Western
      European sample, personal activities in the US sample and professional activities
      in the Japanese sample. Almost half of individuals with sleep problems had never
      taken any steps to resolving them, and the majority of respondents had not spoken
      with a physician about their problems. Of those individuals who had consulted a
      physician, drug prescriptions had been given to approximately 50% in Western
      Europe and the USA and 90% in Japan. CONCLUSIONS: Sleeping problems continue to
      present a considerable burden across Western Europe, the USA and Japan. Despite
      this, they are under-reported and under-treated, with almost half of affected
      individuals not taking any steps to resolve their sleeping problems.

PMID- 18070384
TI  - Interference effects in photoacoustic and reflectance spectroscopies on TiO2/Si
      structures and TiO2 band gap.
AB  - Experimental results of photoacoustic (PAS) and reflectance (RS) spectroscopies
      of titanium dioxide thin films (TiO2), deposited on Si substrates, are compared
      in a wide optical range including transparent and absorbent regions of TiO2. Due
      to the fact that the light modulation frequency f used in the photoacoustic
      experiments was so low that the thermal diffusion length of the TiO2 (mu = 100
      microm) is always larger than the thickness of the studied films, the PAS turns
      out to be complementary to RS over the entire range. The presence of multiple
      reflection interference effects makes difficult a direct evaluation of the TiO2
      band gap from the PAS signal. However, by employing k(lambda) values, obtained
      from transmission experiments on equivalent TiO2 films deposited on transparent
      fused quartz substrates, the PAS spectra for the films deposited on silicon are
      reconstructed by using those theoretical models that consider multiple
      reflections. The reasonable agreement of the simulated and experimental PAS
      spectra allows one to obtain reliable Eg values for the TiO2 films deposited on
      opaque silicon substrates.

PMID- 18070385
TI  - Characterization of novel Ag on TiO2 films for surface-enhanced Raman scattering.
AB  - Novel Ag on TiO2 films are generated by semiconductor photocatalysis and
      characterized by ultraviolet-visible (UV/Vis) spectroscopy, scanning electron
      microscopy (SEM), and atomic force microscopy (AFM), as well as assessed for
      surface-enhanced Raman scattering (SERS) activity. The nature and thickness of
      the photodeposited Ag, and thus the degree of SERS activity, is controlled by the
      time of exposure of the TiO2 film to UV light. All such films exhibit the optical
      characteristics (lambda(max) congruent with 390 nm) of small (< 20 nm) Ag
      particles, although this feature becomes less prominent as the film becomes
      thicker. The films comprise quite large (> 40 nm) Ag islands that grow and merge
      with increasing levels of Ag photodeposition. Tested with a benzotriazole dye
      probe, the films are SERS active, exhibiting activity similar to that of 6-nm
      thick vapor-deposited films. The Ag/TiO2 films exhibit a lower residual standard
      deviation (approximately 25%) compared with Ag vapor-deposited films
      (approximately 45%), which is, however, still unacceptable for quantitative work.
      The sample-to-sample variance could be reduced significantly (< 7%) by spinning
      the film during the SERS measurement. The Ag/TiO2 films are mechanically robust
      and resistant to removal and damage by scratching, unlike the Ag vapor-deposited
      films. The Ag/TiO2 films also exhibit no obvious loss of SERS activity when
      stored in the dark under otherwise ambient conditions. The possible extension of
      this simple, effective method of producing Ag films for SERS, to metals other
      than Ag and to semiconductors other than TiO2, is briefly discussed.

PMID- 18070386
TI  - Resolution of intermediate adsorbate structures in the potential-dependent self
      assembly of n-hexanethiolate on Silver by in situ surface-enhanced Raman
      spectroscopy.
AB  - Resolution of the reaction steps and the associated component Raman spectra
      during the formation or desorption of self-assembled monolayers is challenging
      because intermediate adsorbate populations are present at low concentrations and
      their spectral bands overlap. By collecting Raman spectra versus applied
      potential into a two-dimensional data set, one can utilize multivariate
      statistical techniques to resolve the component concentration profiles along with
      their corresponding Raman spectra. In situ surface-enhanced Raman spectroscopy
      (SERS) spectra were collected during the potential-dependent formation and
      desorption (-1.50 to -0.70V versus Ag/AgCl) of n-hexanethiolate monolayer at a
      polycrystalline Ag electrode. Resolution of the pure component spectra from these
      components was accomplished by using self-modeling curve resolution (SMCR), which
      does not require a physical model. For monolayer adsorption, the potential
      dependent Raman spectra could be described by three significant eigenvectors; the
      eigenvectors could be rotated into a set of pure component spectra and
      concentration profiles using a linear least-squares step to find a common plane
      in the space of the eigenvectors representing the linear combination of the real
      component responses. The convex hull surrounding the data in the plane and
      positive amplitude criteria were utilized to identify the coordinates of the pure
      component responses. The C-S stretching vibrations of the resolved spectra show
      that the initial adsorbate is a gauche conformer, which allows the hydrocarbon
      chain to lie on the metal surface; a second phase arises at higher coverage with
      trans C-S conformation, where the hydrocarbon chains are oriented off the surface
      plane, and a final complete monolayer is formed with a well-ordered, all-trans C
      S configuration. In contrast, desorption studies showed only two surface phases,
      the initial well-ordered monolayer and the low-density phase dominated by gauche
      conformations. The results illustrate the utility of self-modeling curve
      resolution to unravel interfacial reaction mechanisms and intermediate structures
      from two-dimensional SERS data, without requiring prior knowledge of a physical
      model for the process.

PMID- 18070388
TI  - Fourier transform infrared spectroscopic investigation of the electric-field
      induced reorientation of the nematic 7CPB with different prealignment.
AB  - Time-resolved Fourier transform infrared (FT-IR) polarization spectroscopy was
      employed to study the electric-field-induced reorientation of nematic p
      cyanophenyl-p-n-heptylbenzoate (7CPB) in the bulk of the cell and near (within 1
      microm) the surface of the electrodes. The initial orientation of 7CPB on the
      germanium electrodes was varied in order to obtain information concerning the
      behavior of the liquid crystalline molecules in the boundary region. Model
      systems containing the 7CPB on rubbed polyimide and poly(vinyl alcohol), non
      rubbed polyimide and poly(vinyl alcohol), and blank germanium were prepared and
      investigated.

PMID- 18070387
TI  - Potential-dependent surface-enhanced Raman scattering from adsorbed thiocyanate
      for characterizing silver surfaces with improved reproducibility.
AB  - Surface-enhanced Raman scattering (SERS) spectroelectrochemistry is used to
      characterize electrochemically roughened and highly polished polycrystalline
      silver SERS-active substrates. Changes in the nitrile stretching vibrational mode
      of adsorbed thiocyanate are used as an in situ spectroscopic probe: the potential
      dependence of band position (Stark tuning), shape, and scattering intensity of
      this mode are measured in order to investigate differences between SERS-active
      sites found on smooth and roughened electrode surfaces. Results obtained from
      thiocyanate adsorbed onto two different types of highly polished Ag surfaces
      (alumina and diamond polishing) show discrete populations of SERS-active
      adsorption sites that remain stable over a wide potential range. This behavior
      stands in contrast to that observed on electrochemically roughened surfaces,
      where very strong Stark tuning, large vibrational bandwidths, and irreversible
      loss of SERS enhancement upon negative potential excursions can be attributed to
      a diverse population of labile SERSactive sites that exhibit strong charge
      transfer interactions with the adsorbate and large chemical SERS enhancement.

PMID- 18070389
TI  - Development of attenuated total reflection based compression modulation step-scan
      Fourier transform infrared spectroscopy and its applications to rheo-spectral
      characterizations of polymer films.
AB  - Dynamic compression modulation attenuated total reflection Fourier transform
      infrared (ATR FT-IR) spectroscopic methods have been developed in this paper for
      characterizing polymer films. To obtain dynamic compression polarized ATR
      spectra, internal reflection element (IRE) secure assemblies made of tungsten
      carbide with very high hardness (Knoop hardness of > 1000 kgf/mm(2)) have been
      designed. These assemblies are mounted on the Harrick Seagull ATR attachment and
      measured by step-scan FT-IR spectroscopy. The effect of static compression, air
      gaps, and refractive index changes were examined. Experimental and simulated
      results showed that the effect of air gaps between the sample and IRE and
      refractive index changes of the sample and IRE are negligible at values larger
      than a static torque of 40 cN m and good signal-to-noise ratios (SNR) and
      reproducible data can be obtained. Uniaxially and biaxially drawn poly(ethylene
      terephthalate) films were measured by the presented method. Both bipolar and
      unipolar bands were observed in the dynamic in-phase ATR spectra, which can be
      associated with their micro-structural environmental changes. This technique
      shows promise in evaluating various polymer film materials, including biaxially
      oriented films, multilayer coated film surfaces, and molecular interactions
      between polymer-polymer and polymer-additives at the film surface.

PMID- 18070390
TI  - Contribution of semi-quantum dielectric function models to the analysis of
      infrared spectra.
AB  - A new approach to modeling using semi-quantum dielectric function models is
      proposed for the retrieval of the optical functions from infrared spectra. The
      powerful points of the method are shown throughout the analysis of two
      semitransparent materials, MgO and KBr. All the results are discussed in light of
      those obtained with classical techniques. This type of model is able to retrieve,
      for example, the extinction index in a range that covers at least six orders of
      magnitude and gives access to highly valuable information about high-order phonon
      processes.

PMID- 18070391
TI  - Indirect spectral hard modeling for the analysis of reactive and interacting
      mixtures.
AB  - We present an indirect hard modeling (IHM) approach for the quantitative analysis
      of reactive multicomponent mixtures with intermolecular interaction. It can be
      used when it is not possible to obtain calibration data in the composition region
      of interest. The goal of this work, specifically, is to analyze reactive systems,
      although the validation of the method is done with nonreactive systems. Compared
      to conventional hard modeling, the new approach reduces the manual work required
      for modeling and renders unnecessary the assignment of bands in mixture spectra
      to individual components. It is based on parametric models of the pure component
      spectra that are made just flexible enough to fit the spectra of the unknown
      mixtures, and it only requires small calibration data sets that may lie in
      different regions of the composition space. The application to infrared (IR) and
      Raman spectra of multicomponent systems is discussed.

PMID- 18070392
TI  - Automatic generation of peak-shaped models.
AB  - We describe how parametric spectral models for analytical applications can be
      generated by an automatic curve-fitting algorithm. The algorithm does not require
      initial choices of parameters or other human intervention, in contrast to
      established approaches that rely on deconvolution or derivative spectroscopy.
      This algorithm has been applied for quantitative analysis but can potentially be
      used in other applications that are based on parametric representations of peak
      shaped models or could benefit from using such models, such as calibration
      transfer.

PMID- 18070393
TI  - Characterization of infrared and near-infrared absorptions of free alcoholic OH
      groups in hydrocarbon.
AB  - We have demonstrated that the near-infrared and infrared absorptions in the 8000
      3200 cm(-1) region of an OH group of 2-nonanol, 1-nonanol, etc., in n-heptane are
      excellently separated by subtraction without any serious interference down to
      very low concentrations at which OH groups are completely free. The separated
      sharp absorptions are assigned to the fundamental, combination, and overtone
      bands that are concerned with the OH stretching of free OH. Two components of a
      sharp overtone band around 7100 cm(-1), which are observed for primary and
      secondary alcohols, are assigned to coexisting internal rotational isomers of an
      OH group around the O-C bond. The frequencies of the OH stretching fundamental
      and overtone bands that are assigned to internal rotational positions are
      consistent for all the investigated alcohols, including methanol and tertiary
      butanol. Comparison of the separated spectrum of 2-nonanol in n-heptane with that
      in 1-chlorooctane or in carbon tetrachloride makes it clear that hydrocarbon is
      an inert solvent that does not disturb the intrinsic nature of an alcohol OH
      group. There actually exists a constant anharmonicity shift of 169-175 cm(-1)
      between the double frequency (2nu(OH)o) of the observed fundamental and the
      observed overtone frequency ([2nu(OH)]o) for free OH of various alcohols in n
      heptane.

PMID- 18070394
TI  - Dual-wavelength time-resolved resonance ionization imaging with cesium and
      mercury vapors.

PMID- 18070398
TI  - Fourier transform infrared imaging of stereoregular poly(methyl methacrylate)
      dissolution.
AB  - Fourier transform infrared (FT-IR) imaging was used to study dissolution of
      stereoregular poly(methyl methacrylate) (PMMA) films in toluene, benzene,
      chloroform, acetic acid, and 2-ethoxyethanol. Images of the polymer-solvent
      interface showed that syndiotactic (sPMMA), atactic (aPMMA), and isotactic
      (iPMMA) samples dissolved in acetic acid and chloroform; only iPMMA dissolved in
      benzene, toluene, and 2-ethoxyethanol. Concentration profiles allowed
      quantitative comparison of each polymer-solvent system. In the cases of
      chloroform and acetic acid, the rate of polymer dissolution increased with
      increasing isotacticity. Dissolution of PMMA in chloroform was observed to
      coincide with development of strong polymer-solvent interactions. The results of
      systems containing toluene, benzene, and 2-ethoxyethanol reflect kinetic effects
      on dissolution, including solvent size and stiffness of the polymer backbone.

PMID- 18070399
TI  - Studies of liquid-phase complexes in acetonitrile/water solutions by attenuated
      total reflection infrared spectroscopy with acetaldehyde as a model solute.
AB  - Chemometric methods combined with infrared (IR) spectroscopy, using attenuated
      total reflectance (ATR) sampling, are employed here to characterize the
      stoichiometry of complexes of solvent molecules in the liquid phase. The spectral
      information provides insight into the liquid microstructure present in liquid
      chromatographic mobile phases. This information should make it easier to
      understand and predict the effects of changes in mobile phase composition on the
      results of chromatographic separations. In this paper, mobile phases consisting
      of 0 mol % to 100 mol % acetonitrile in water were studied, with the addition of
      acetaldehyde as a model solute at concentrations ranging from 3 to 8 mol %. Using
      three-way multivariate curve resolution by the alternating least squares method
      (MCR-ALS) it was possible to resolve eight unique spectra: four mobile phase
      components, and four unique spectra of acetaldehyde solvated in different
      environments. The directions of the shifts of the important acetaldehyde infrared
      bands show good correlation with those predicted by gas-phase ab initio
      calculations of small solvated clusters.

PMID- 18070400
TI  - Prediction of ethylene content in melt-state random and block polypropylene by
      near-infrared spectroscopy and chemometrics: comparison of a new calibration
      transfer method with a slope/bias correction method.
AB  - This paper reports the prediction of the ethylene content (C2 content) in random
      polypropylene (RPP) and block polypropylene (BPP) in the melt state by near
      infrared (NIR) spectroscopy and chemometrics. NIR spectra of RPP and BPP in the
      melt states were measured by a Fourier transform near-infrared (FT-NIR) on-line
      monitoring system. The NIR spectra of RPP and BPP were compared. Partial least
      squares (PLS) regression calibration models predicting the ethylene (C2) content
      that were developed by using each RPP or BPP spectra set separately yielded good
      results (SECV (standard error of cross validation): RPP, 0.16%; BPP, 0.31%;
      correlation coefficient: RPP, 0.998; BPP, 0.996). We also built a common PLS
      calibration model by using both the RPP and the BPP spectra set. The results
      showed that the common calibration model has larger SECV values than the models
      based on the RPP or the BPP spectra sets individually and is not practical for
      the prediction of the C2 content. We further investigated whether a calibration
      model developed by using the BPP spectra set can predict the C2 contents in the
      RPP sample set. If this is possible, it can save a significant amount of work and
      cost. The results showed that the use of the BPP model for the RPP sample set is
      difficult, and vice versa, because there are some differences in the molar
      absorption coefficients between the RPP and BPP spectra. To solve this problem, a
      transfer method from one sample spectra (BPP) set to the other spectra (RPP) set
      was studied. A difference spectrum between an RPP spectrum and a BPP spectrum was
      used to transfer from the BPP calibration set to the RPP calibration set. The
      prediction result (SEP (standard error of prediction), 0.23%, correlation
      coefficient, 0.994) of RPP samples by the transferred calibration set and model
      showed that it is possible to transfer from the BPP calibration set to the RPP
      calibration set. We also studied the transfer from the RPP calibration set (the
      range of C2 content: 0-4.3%) to the BPP calibration set. The prediction result of
      C2 content (the range of C2 contents: 0-7.7%) in BPP by use of the calibration
      model based on the transferred BPP spectra from the RPP spectra showed that the
      transfer method is only effective for the interpolation of the C2 content range
      by the nonlinear change in the peak intensities with the C2 content.

PMID- 18070401
TI  - Determination of spectrometer-detector parameters from calibration spectra and
      the use of the parameters in spectrometer calibrations.
AB  - The grating equation is used to generate quadratic calibration equations for
      multichannel detectors with perpendicular and tilted focal planes. The quadratic
      coefficients are not independent and contain terms that are used to solve for
      spectrometer-detector parameters. The parameters can be calculated from a
      quadratic fit at one spectrometer position, but more accurate values can be
      obtained from quadratic fits at two spectrometer positions. The calculations show
      that the detector focal plane is tilted by about two degrees. Once values for the
      spectrometer-detector parameters are obtained from calibrations using at least
      three lines at one or two spectrometer positions, only one calibration line at
      any spectrometer position is required to obtain accuracies on the order of 0.1
      cm(-1) over a several thousand wavenumber range. The main cause of spectrometer
      drift is a change in the diffraction angle and/or the spectrometer included
      angle. This drift is almost totally compensated by the one-line calibration,
      which adjusts the diffraction angle. A neon pen lamp is used to generate the
      calibration spectra. Using standard air wavelengths compared to true wavelengths
      can produce calibration errors of 0.1 to 0.6 cm(-1); the magnitude depends on
      local conditions and how the laser wavelength is treated.

PMID- 18070402
TI  - Electrothermal atomic absorption spectrometric determination of gold by vapor
      formation and in situ trapping in graphite tubes.
AB  - Gold was determined in ore samples following generation, separation, collection
      on a graphite cuvette inner wall, and atomization of its volatile species formed
      by combining an acidified sample solution with an aqueous sodium tetrahydroborate
      solution at room temperature. A detection limit of 2.6 microg L(-1) (3sigma) was
      obtained with a 5.0 mL sample volume. Precision of replicate measurements was
      typically 10% RSD. The overall efficiency of the volatile species generation,
      transport, and trapping process was 0.4%. Atomization of gold from Pd, Ir, Cu,
      Ag, and W coated graphite cuvettes, following by trapping of the gaseous volatile
      gold species on these surfaces, has been investigated. Pd coating was found to
      decrease the sensitivity. Five microg of Ir, 20 microg of Cu, 20 microg of Ag,
      and 5 microg of W were chosen as optimum masses. W treatment was the best one for
      sensitivity enhancement, having an improvement factor of 2.4. Silanization of
      glass surfaces significantly decreased memory effects; improved peak shapes were
      thus obtained for flow injection vapor generation atomic absorption spectrometry
      (FI-VGAAS). The method described in this study was used for the determination of
      gold in an ore reference material, Gold Ore (MA-1b), Canadian Reference Materials
      Program.

PMID- 18070403
TI  - A mathematical model for analyzing infrared polar diagrams from polymer fibers.

PMID- 18070405
TI  - Microscopic infrared mapping of chloromethylated polystyrene resin beads.
AB  - In solid-phase combinatorial chemistry, analyses are performed using a wide range
      of analytical techniques ranging from gel-phase nuclear magnetic resonance (NMR)
      to colorimetric tests to elemental analysis. However, these techniques cannot be
      used to interrogate functional group distribution at the single-bead level. This
      paper explores the feasibility of using Fourier transform infrared (FT-IR)
      microscopy to examine site distribution on chloromethylated polystyrene resin
      beads and to quantify the loading after coupling with 4-cyanophenol, an IR
      tagging agent. FT-IR microscopy also provides a unique opportunity to better
      understand the reactivity of highly cross-linked polymer beads under a range of
      chemical conditions.

PMID- 18070406
TI  - Study of a chemically amplified resist for X-ray lithography by Fourier transform
      infrared spectroscopy.
AB  - Future applications of microelectromechanical systems (MEMS) require lithographic
      performance of very high aspect ratio. Chemically amplified resists (CARs) such
      as the negative tone commercial SU-8 provide critical advantages in sensitivity,
      resolution, and process efficiency in deep ultraviolet, electron-beam, and X-ray
      lithographies (XRLs), which result in a very high aspect ratio. In this
      investigation, an SU-8 resist was characterized and optimized for X-ray
      lithographic applications by studying the cross-linking process of the resist
      under different conditions of resist thickness and X-ray exposure dose. The
      exposure dose of soft X-ray (SXR) irradiation at the average weighted wavelength
      of 1.20 nm from a plasma focus device ranges from 100 to 1600 mJ/cm(2) on the
      resist surface. Resist thickness varies from 3.5 to 15 mum. The cross-linking
      process of the resist during post-exposure bake (PEB) was accurately monitored
      using Fourier transform infrared (FT-IR) spectroscopy. The infrared absorption
      peaks at 862, 914, 972, and 1128 cm(-1) in the spectrum of the SU-8 resist were
      found to be useful indicators for the completion of cross-linking in the resist.
      Results of the experiments showed that the cross-linking of SU-8 was optimized at
      the exposure dose of 800 mJ/cm(2) for resist thicknesses of 3.5, 9.5, and 15
      microm. PEB temperature was set at 95 degrees C and time at 3 min. The resist
      thickness was measured using interference patterns in the FT-IR spectra of the
      resist. Test structures with an aspect ratio 3:1 on 10 microm thick SU-8 resist
      film were obtained using scanning electron microscopy (SEM).

PMID- 18070407
TI  - A spectral identity mapper for chemical image analysis.
AB  - Generating chemically relevant image contrast from spectral image data requires
      multivariate processing algorithms that can categorize spectra according to
      shape. Conventional chemometric techniques like inverse least squares, classical
      least squares, multiple linear regression, principle component regression, and
      multivariate curve resolution are effective for predicting the chemical
      composition of samples having known constituents, but they are less effective
      when a priori information about the sample is unavailable. We have developed a
      multivariate technique called spectral identity mapping (SIM) that reduces the
      dependence of spectral image analysis on training datasets. The qualitative SIM
      method provides enhanced spectral shape specificity and improved chemical image
      contrast. We present SIM results of spectral image data acquired from polymer
      coated paper substrates used in the manufacture of pressure sensitive adhesive
      tapes. In addition, we compare the SIM results to results from spectral angle
      mapping (SAM) and cosine correlation analysis (CCA), two closely related
      techniques.

PMID- 18070408
TI  - High-resolution two-grating spectrometer for dual wavelength spectral imaging.
AB  - A two-grating high-resolution spectrometer for dual wavelength imaging is
      demonstrated based on the standard Czerny-Turner mounting with an auxiliary
      grating and a mirror. A two-dimensional charge-coupled device (CCD) detector in
      the spectrometer focal plane allows simultaneous detection of two spectral
      intervals. Each spectrometer grating is driven by a high-precision stepper motor
      interfaced to a computer via home-made software. The software allows fast tuning
      of the gratings to a desirable spectral interval anywhere between 200 nm and 800
      nm. The spectral interval widths are 2-3 nm for a ''high-resolution'' (2400
      grooves/mm) grating and 4-5 nm for a ''low-resolution'' (1200 grooves/mm)
      grating. The resolution varies between 0.01 nm and 0.02 nm depending on the
      grating used. The performance of the spectrometer is demonstrated by detecting
      spectrally resolved images from a back-illuminated template and from a laser
      induced plasma. The spectrometer can be useful for two-line spectroscopic
      diagnostics or can be expanded for multi-element spectral analysis.

PMID- 18070409
TI  - Real-time monitoring of high-temperature corrosion in stainless steels by open
      path laser-induced plasma spectrometry.
AB  - Open-path laser-induced plasma spectrometry (OP-LIPS) represents an appealing
      alternative for the real-time monitoring of high-temperature processes due to its
      inherent non-invasive and remote capabilities. In this work, stainless steel
      samples have been analyzed at 10 meters from the laser source. The effect of the
      high-temperature conditions to the protective anti-corrosion layer have been
      analyzed, as well as additional factors such as the type of steel and the
      exposure time. The number of pulses required to ablate the alteration layer has
      been found to follow a linear relationship with the square root of the exposure
      time, in excellent agreement with the off-line thermogravimetric measurements
      described in the literature.

PMID- 18070410
TI  - Theoretical modeling of optimal focusing conditions using laser-induced breakdown
      spectroscopy in liquid jets.
AB  - Optimal conditions are determined for laser-induced breakdown spectroscopy in
      liquid jets by investigating laser de-focusing and laser energy variation in
      aqueous liquid jets containing dilute levels of calcium chloride. It has been
      found that the atomic emission shows a strong correlation with both laser pulse
      energy and focal position. The data cannot be rationalized on the basis of
      electron density or ionization temperature changes alone, but rather it requires
      the additional consideration of the volume of the liquid sample interacting with
      the laser and that portion of the volume which is above the threshold energy for
      plasma formation. A moving breakdown model has been applied to the plasma
      formation in the jet to calculate the amount of sample ablated with sufficient
      energy for plasma formation, which models well the observed results and allows
      prediction of optimal focusing conditions for a given laser energy.

PMID- 18070411
TI  - New spectral optovoltaic effect in optically thick neutral cesium vapor.

PMID- 18070412
TI  - A webcam as a light probe beam profiler.

PMID- 18070415
TI  - The power of informatics.

PMID- 18070416
TI  - A new mutation within the porphobilinogen deaminase gene leading to a truncated
      protein as a cause of acute intermittent porphyria in an extended Indian family.
AB  - Based on Internet search, we were contacted by a 50-year-old man suffering from
      severe abdominal pain. Acute hepatic porphyria was considered from positive
      Watson-Schwartz test. He, not being a health professional, searched for centres
      with ability to do molecular diagnosis and for information about therapeutic
      possibilities. He asked his physician for haem-arginate (Normosang, Orphan
      Europe, Paris) treatment, arranged sending his blood to our laboratory and
      mediated genetic counselling for him and his family. Molecular analyses of the
      PBGD gene revealed a novel mutation in exon 15, the 973insG. Subsequently,
      genetic analysis was performed in 18 members of the proband's extensive family.
      In 12 members of the family, the same mutation was found. The mutation, which
      consisted of one nucleotide insertion, resulted in addition of four different
      amino acids leading to a protein that is prematurely truncated by the stop codon.
      The effect of this mutation was investigated by expression of the wildtype and
      mutated PBGD in a prokaryotic expression system. The mutation resulted in
      instability of the protein and loss of enzymatic function. The increasing access
      to a number of disease- and symptom-oriented web pages presents a new and unusual
      venue for gaining knowledge and enabling self-diagnosis and self-help. It is,
      therefore, important that diseaseoriented Internet pages for public use should be
      designed with clarity and accurate current knowledge based background.

PMID- 18070417
TI  - Variants within the ghrelin gene--association with HDL-cholesterol, but not with
      body mass index.
AB  - Ghrelin is a hormone which influences eating habits, the amount of food ingested
      and the body's energy balance. We examined whether genetic variants in the
      ghrelin gene are associated with BMI, WHR and plasma lipid levels. We have
      evaluated the influence of ghrelin polymorphisms (Arg51>Gln, Leu72>Met and
      Gln90>Leu) on BMI, WHR, and plasma lipid levels in 1,191 males and 1,368 females
      representatively selected from the Czech population. Anthropometrical and
      biochemical parameters were analysed in two different years. In the entire
      population, we have detected 4.8% of carriers of the Gln51 allele, 14.2% carriers
      of the Met72 allele, and 10.9% of the Leu90 allele. Frequencies did not differ
      between males and females and alleles were not in linkage disequilibrium. BMI or
      WHR were not influenced by variants in the ghrelin gene. The ghrelin variant
      Leu72>Met was associated with elevated levels of plasma HDL-cholesterol. Compared
      to Leu/ Leu homozygotes, the Met carriers had lower HDL-cholesterol
      concentrations in males (1.18 +/- 0.29 mmol/l vs. 1.24 +/- 0.35 mmol/l, P = 0.01)
      as well as in females (1.45 +/- 0.35 mmol/l vs. 1.51 +/- 0.38 mmol/l, P = 0.01).
      The other lipid parameters (total cholesterol and triglycerides) were not
      associated with this variant. There were no associations between other ghrelin
      variants (Arg51>Gln and Gln90>Leu) and analysed biochemical parameters. We
      conclude that in the Caucasian population, variations in the ghrelin gene could
      play a role in genetic determination of plasma levels of HDL-cholesterol, but
      they have no effect on BMI or WHR.

PMID- 18070418
TI  - Downregulation of myc promoter-binding protein 1 (MBP-1) in growth-arrested
      malignant B cells.
AB  - Normal human B lymphocytes are sensitive to the growth-inhibitory action of TGF
      beta1 whereas malignant B lymphoma cells are mostly resistant to TGF-beta1
      effects. We have shown in our previous work that, TGF-beta1 treatment resulted in
      significant growth inhibition of the DoHH2 cell line. In the present study we
      showed that TGF-beta1-induced growth arrest was associated with notable
      downregulation of the myc-binding protein-1 (MBP-1). Moreover, our results
      indicated that c-Myc overexpression in TGF-beta1-arrested malignant B cells is
      mediated by binding of MBP-1, as a transcription repressor, to the (+118/+153)
      element of the promoter region of the myc gene.

PMID- 18070419
TI  - Multiplex analysis of cytokines involved in tumour growth and spontaneous
      regression in a rat sarcoma model.
AB  - The aim of our study was to examine in vivo and in vitro cytokines produced by
      Lewis ratderived R5-28 sarcoma cells. These cells produce rapidly growing tumours
      in approximately two weeks after subcutaneous inoculation. However, spontaneous
      tumour regression was noted in about 40% of animals. For an explanation of this
      phenomenon, we evaluated the profile of 19 cytokines during tumour growth and
      spontaneous regression by the use of "antibody array". To detect cytokines
      directly originated by the sarcoma, the R5-28 cells were cultivated in vitro and
      then both the supernatants and the cell lysates were analysed. Our experiments
      showed three cytokines (MCP-1, TIMP-1 and VEGF) to be produced by R5-28 cells in
      vitro. Moreover, in vivo, another three cytokines (TNF-alpha, beta-NGF and LIX)
      were detected both in blood sera and tumour lysates, probably produced by immune
      and stromal cells during tumour growth. Changes in their expression after
      spontaneous regression are discussed.

PMID- 18070420
TI  - The effect of interferon beta-1a on MMP-2 and MMP-9 proteolytic activity.
AB  - MMP-2 and MMP-9 play a significant role in the development of numerous diseases
      mainly with the inflammatory pathogenesis. One of the drugs exerting an effect on
      metalloproteinases is IFN-beta. Previous studies showed that IFN beta-1b can
      decrease MMP synthesis and moreover inhibit their proteolytic activity. The aim
      of our study was to analyse the influence of recombinant IFN beta-1a (identical
      with natural IFN-beta) on MMP-2 and MMP-9 activities. The gelatinolytic activity
      was evaluated with zymography in sera obtained from 10 healthy donors. After
      electrophoresis gels were incubated with or without IFN beta-1a (2000 U/ml) for
      18 h. We noticed a significant decrease of MMP-2/72 kDa (P = 0.0283) and the
      augmentation of MMP-9/92 kDa (P = 0.0042) activities after incubation with
      interferon. The elevation of MMP-9/92 kDa activity suggests that IFN beta-1a can
      exhibit proinflammatory features besides well-known anti-inflammatory properties.

PMID- 18070421
TI  - Article retraction.

PMID- 18070422
TI  - [Utilize science and technology achievements effectively in China].

PMID- 18070423
TI  - [Longitudinal changes of posterior available spaces of lower dental arch in
      adolescents with normal occlusion from 13 to 18 years of age].
AB  - OBJECTIVE: To investigate the changes of available spaces of posterior arch
      segments in mandibular dentition from 13 to 18 years of age, which would provide
      information for space analysis of whole dental arch in adolescents. METHODS:
      Twenty-six adolescents (12 males, 14 females) with normal occlusion were
      selected. All of the subjects had lateral cephalograms taken at the same time
      each year for 6 years. Longitudinal cephalometry and statistic analysis were
      conducted for all subjects. RESULTS: Significant differences of available space
      were found between males and females. The growth of available space from 13 to 18
      years of age was 5.12 mm in females and 5.79 mm in males. The completion of
      mandibular remodeling in males lagged behind females for about 1 year. No
      significant increase was found in girls beyond 16 years and in boys beyond 17
      years. There was a 1.22 mm increase on each side per year in females until 16
      years and a 1.45 mm increase in males until 17 years. The increase of available
      space was made partly by resorption of bone from the anterior border of the ramus
      and partly by mesial movement of the first molar. The mesial movement of dental
      arch was probably stimulated by the eruption of the third molars. CONCLUSIONS:
      The prediction of available space should be based on age and sex.

PMID- 18070424
TI  - [Treatment effects of magnetic Twin-block appliance for class II cases].
AB  - OBJECTIVE: To evaluate the effects of magnetic Twin-block appliance in the
      treatment of skeletal class II cases. METHODS: The magnetic Twin-block appliance
      was embedded with two pairs of neodymium-iron-boron (Nd(2)Fe(14)B) rare earth
      permanent magnets in the upper and lower inclined planes of Twin-block appliance.
      The sample comprised of 13 skeletal class II patients in the late mixed or early
      permanent dentition treated by magnetic Twin-block appliance. Cephalometric films
      were taken before and after treatment. Helix CT images of the temporomandibular
      joint (TMJ) in all patients were examined before treatment (T1), during treatment
      (4 months after appliance placement, T2), after treatment (T3) and one year after
      treatment (T4). RESULTS: A double contour image was detected in the superior
      posterior part of the condylar head on the pseudo-sagittal reconstruction plane
      pictures of T2 in 11 patients. The double contour image could be observed in most
      patients as well. This image also exhibited on the pictures of T3 in several
      patients. On the pictures of T2 and T3 in some patients, interruption of cortical
      bone and "bifurcation phenomenon" of condyles were shown. Pictures of T1 and T4
      were similar and no signs of remodeling of TMJ were observed. Cephalometric
      analysis revealed significant changes in the maxillofacial structure after
      treatment. The profile of patients improved. CONCLUSIONS: Bone remodeling of
      condyle occurred during the magnetic Twin-block treatment in class II patients.
      Magnetic Twin-block appliance was effective in the treatment of the growing
      skeletal class II patients.

PMID- 18070425
TI  - [Bending mechanical properties of NiTi round wire].
AB  - OBJECTIVE: To investigate the bending mechanical properties and provide reference
      for orthodontists to select the proper wires during alignment stage. METHODS: In
      order to analyze the load deflection rate of NiTi round wire quantitatively, some
      NiTi round wires of different cross-sectional dimension (0.36, 0.41, 0.46 mm)
      were selected. Then loading-unloading experiments were carried out with the micro
      orthodontic archwire testing apparatus and double end bending test could be
      accomplished with the wire in a 0.56 mm x 0.71 mm standard incisor edgewise
      bracket slot. RESULTS: Under the load of 0.03 N.m, 0.36 and 0.41 mm NiTi round
      wire showed excellent super-elasticity, while 0.46 mm NiTi round wire didn't.
      When the optimal moment produced by the archwire was between 0.01 N.m and 0.02
      N.m, the bending range of 0.36, 0.41 and 0.46 mm NiTi round wires was from 21.0
      degrees to 49.5 degrees , 7.2 degrees to 23.7 degrees , and 6.5 degrees to 9.5
      degrees , respectively after deducting the contact angle. CONCLUSIONS: On the
      premises of yielding effective orthodontic force, the preferable NiTi round wire
      for alignment was the one which could produce continuous and slowly declining
      force.

PMID- 18070426
TI  - [Early-response of the condylar chondrocyte under cyclic uniaxial compressive
      stress].
AB  - OBJECTIVE: To investigate the protein profile after treatment of the cyclic
      uniaxial compressive stress on the rat condylar chondrocyte in vitro. METHODS:
      The third-passage chondrocytes were harvested from the mandibular condyles of 2
      day-old rats, and a cellular compressive stress device (self-made four-point
      bending system) was used to apply stress on cells at 2000 microstrain and 4000
      microstrain (0.5 Hz frequency) for 60 min. The early effects of cyclic uniaxial
      compressive stress on the protein profile of the rat mandibular condylar
      chondrocytes were examined by two dimensional polyacrylamide gel electrophoresis
      (2D-PAGE) and matrix-assisted laser-desorption ionization time of flight mass
      spectrometry (MALDI-TOF-MS). RESULTS: The results showed that the protein profile
      of the condylar chondrocyte did not change statistically in 2000 microstrain
      group. In 4000 microstrain group, the protein profile of the condylar chondrocyte
      was changed. Three new proteins appeared. Five proteins disappeared. Twenty-two
      proteins were down-regulated and 7 proteins were up-regulated (P < 0.05). The
      eight different protein spots were identified by MALDI-TOF-MS. It included
      cytoskeleton protein (gamma-actin and vimentin), glycometabolism protein (alpha
      enolase and stress-70 protein) and signal transduction protein (Raf kinase
      inhibited protein, RKLP). CONCLUSIONS: There were significant alternations of the
      protein profile in the rat condylar chondrocyte after the 4000 microstrain cyclic
      uniaxial compressive stress loading for 60 min. These different proteins might
      take part in the early response to the cyclic uniaxial compressive stress.

PMID- 18070428
TI  - [Progress of Chinese orthodontics].

PMID- 18070427
TI  - [The expression of estrogen receptors in the human periodontal ligament
      fibroblasts in vitro].
AB  - OBJECTIVE: To explore the expression of estrogen receptors in the human
      periodontal ligament fibroblasts in vitro. METHODS: Human periodontal ligament
      fibroblasts were cultured in vitro. The estrogen receptors (ER)-alpha, ER-beta
      were detected with immunocytochemistry staining; The mRNA of ER-alpha, ER-beta
      were measured by reverse transcription polymerase chain reaction; The expression
      of ER-alpha, ER-beta protein were detected by Western blot. RESULTS: The mRNA and
      protein expression of two subtype of ER were observed on human periodontal
      ligament fibroblasts (HPLF). The intensity of the ER-beta bands were stronger
      than those of ER-alpha, indicating that ER-beta expression in HPLF was higher.
      CONCLUSIONS: ER may play an important role in the function of human periodontal
      ligament fibroblasts.

PMID- 18070429
TI  - [Summary of the Second Cross-strait Four Regions Orthodontic Conference].

PMID- 18070430
TI  - [Relationship between extracapsular spread of cervical metastatic lymph node and
      cervical recurrence in oral cancer patients].
AB  - OBJECTIVE: To investigate the relationship between extracapsular spread (ECS) of
      cervical metastatic lymph node and the recurrence in patients with oral squamous
      cell carcinoma (OSCC). METHODS: The medical records of 74 OSCC patients with
      histologically confirmed cervical lymph node metastasis were reviewed. They were
      divided into 2 groups, ECS positive (ECS+) and ECS negative (ECS-). The treatment
      results were followed up. Statistical analysis, with chi-square test, and
      multiple logistic regression was conducted. RESULTS: The overall recurrence rates
      for pN+/ECS- and pN+/ECS+ patients were 47.6% and 75.0%, respectively, and the
      cervical recurrence rates for pN+/ECS- and pN+/ECS+ patients were 9.5% and 46.9%,
      respectively (P < 0.001). Multivariate analysis showed that ECS was one of the
      independent prognosis factors for cervical recurrence. CONCLUSIONS: Extracapsular
      spread significantly increased both overall and cervical recurrence rates, and
      ESC may be a prognosis factor for OSCC patients.

PMID- 18070431
TI  - [Experimental study on the reconstruction of mandibular symphyseal defects by
      internal tri-focal distractor].
AB  - OBJECTIVE: To introduce the internal tri-focal distractor developed by the
      authors and evaluate its primary application and feasibility in animal
      experiment. METHODS: Four hybrid dogs were selected and segmental resection at
      the mandibular symphysis was performed. Two transfer disks, 10 mm in width, were
      respectively fixed at the two ends of bone defect and the internal tri-focal
      distractor was installed. The force was applied one week after the operation,
      with a tractive speed of 0.5 mm/12 h. After 13 - 16 days, the traction was
      completed when the two transfer disks were combined. The occlusal films were
      taken at the 1st day, 4th, 8th and 12th week after traction. The animals were
      killed at the 12th week, samples of the traction area taken and histological
      examination performed. Finally, the new bone formation was observed. RESULTS: All
      the animals survived in the experiment, abruption and rust-eaten was not found in
      distractor. In the 12th week after installation, new bones in traction gap were
      mature and bony union between the two transfer dishes was accomplished.
      CONCLUSIONS: The internal tri-focal distractor used in this study may become a
      potential device in reconstruction of mandibular symphyseal defects.

PMID- 18070432
TI  - [Influence of iNOS silencing by RNA interference on proliferation activity of
      Tca8113 cell].
AB  - OBJECTIVE: To investigate the apoptosis and proliferation activity of Tca8113
      cells. METHODS: The vector that involves short hairpin RNA of iNOS was
      transfected to Tca8113 cells. The change of iNOS expression was observed using
      immunohistochemistry technique, the apoptosis rate examined by flow cytometry,
      and the proliferation Tca8113 cells examined by methyl thiazolyl tetrazolium
      (MTT). RESULTS: The expression of iNOS in Psilencer-iNOS group was lower than
      that in control groups (P < 0.01), the apoptosis rate was higher than that in
      control groups (P < 0.01); whereas the proliferation activity of Tca8113 cells in
      Psilencer-iNOS group was lower than that in control groups. CONCLUSIONS: Down
      expression of iNOS by RNAi can promotes apoptosis of Tca8113 cells and has an
      anti-proliferation activity effect.

PMID- 18070433
TI  - [Proteomics study of the serum biomarkers in tongue cancer].
AB  - OBJECTIVE: To search for specific serum biomarkers associated with tongue cancer
      by means of the serum proteomics technology. METHODS: The tongue cancer cells of
      human tongue cancer cell line Tca8113 were subcutaneously inoculated into nude
      mice, while control nude mice were injected with phosphate-buffered saline.
      Serums from these two group of mice were collected for proteomic analysis using
      two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). RESULTS:
      Comparing the serum 2-DE maps from the tumor-bearing mice with those produced
      from control mice, we found that squamous cell carcinoma antigen 1 was over
      expressed only in the serum of tumor-bearing mice. CONCLUSIONS: The squamous cell
      carcinoma antigen 1 may be of great potential as the biomarker of tongue cancer
      and as the potential therapeutic target for gene therapy.

PMID- 18070434
TI  - [Clinical and radiographic study of the fractured immature anterior permanent
      teeth after pulpotomy].
AB  - OBJECTIVE: To observe the outcome of the fractured immature anterior permanent
      teeth after pulpotomy by X-ray measurement. METHODS: A total of 31 (25 cases)
      fractured immature anterior permanent teeth after pulpotomy was reviewed.
      Radiographic measurements were performed on 12 cases with unilateral fractured
      central incisors and completely formed roots after pulpotomy and 100 (50
      subjects) healthy maxillary central incisors. RESULTS: The roots development
      continued after pulpotomy, and the root length and periapical configuration were
      both similar to the healthy teeth, but some root canals became narrow or even
      nearly obturated at the root apex. There was no significant difference in root
      canal width between healthy right and left maxillary central incisors at the site
      of 1/4 [right: (0.67 +/- 0.14) mm, left: (0.66 +/- 0.12) mm, P > 0.05], 1/2
      [right: (1.05 +/- 0.19) mm, left: (1.04 +/- 0.17) mm, P > 0.05], 3/4 [right:
      (1.78 +/- 0.34) mm, left: (1.76 +/- 0.30) mm, P > 0.05] of root, but the root
      canal width of the fractured incisors at the same site was significantly
      different from that of the contralateral healthy incisor, the 1/4 site pulpotomy:
      (0.70 +/- 0.23) mm, control: (0.99 +/- 0.17) mm, the 1/2 site pulpotomy: (1.16 +/
      0.24) mm, control: (1.51 +/- 0.25) mm; the 3/4 site pulpotomy: (1.96 +/- 0.34)
      mm, control: (2.24 +/- 0.36) mm. CONCLUSIONS: There was a tendency that the root
      canals of fractured teeth after pulpotomy became narrowed and obturated. It
      should not be followed up for too long to perform root canal treatment when roots
      completely formed.

PMID- 18070435
TI  - [Observation of the influence of chemomechanical caries removal on dentin
      adhesion by scanning electron microscope].
AB  - OBJECTIVE: To observe the influence of chemomechanical caries removal on dentin
      adhesion by scanning electron microscope. METHODS: The ultrastructure of dentin
      surfaces and adhesives-dentin bonding interfaces after caries removal by
      chemomechanical method or drilling were observed. RESULTS: Less smear layer in
      dentin surface, resin tags in the interface between dentin and Prime&Bond
      NT/compomer and numerous resin tags and more uniform and closer hybrid layer in
      the interface between dentin and Adper Prompt-L-Pop/composite were found in
      chemomechanical preparation than in drilling preparation. CONCLUSIONS:
      Chemomechanical caries removal can benefit dentin adhesion.

PMID- 18070436
TI  - [Expression, subcellular localization and nuclear translocation of transcription
      factor up stream stimulatory factor-1 in odontoblasts].
AB  - OBJECTIVE: To examine the expression and subcellular localization of
      transcription factor USF1 in odontoblasts and investigate whether nuclear
      translocation occurs under stimuli. METHODS: Odontoblasts MDPC-23 were cultured
      on coverslips and divided into 2 groups. Group 1 received no stimuli, and group 2
      was stimulated by nicotine with various concentrations respectively for 1h. Then
      the mountings of odontoblasts were prepared and immunocytochemical staining was
      performed with specific USF1 antibody via SABC method. Hela cells were used as
      positive control. RESULTS: The staining was positive in the cytoplasm of
      odontoblasts in group 1, but in the nuclei of Hela cells and in 100 mg/L nicotine
      stimulated odontoblasts in group 2. CONCLUSIONS: There exists USF1 protein in
      odontoblasts, which locates in the cytoplasm and could translocate into nuclei
      under the stimulation of nicotine.

PMID- 18070437
TI  - [Transmission disequilibrium test for nonsyndromic cleft lip and palate and
      segment homeobox gene-1 gene].
AB  - OBJECTIVE: To investigate the relationship between muscle segment homeobox gene-1
      (MSX1) and the genetic susceptibility of nonsyndromic cleft lip and palate
      (NSCLP) in Hunan Hans. METHODS: One microsatellite DNA marker CA repeat in MSX1
      intron region was used as genetic marker. The genotypes of 387 members in 129
      NSCLP nuclear family trios were analyzed by polymerase chain reaction (PCR) and
      denaturing polyacrylamide gel electrophoresis. Then transmission disequilibrium
      test (TDT) and Logistic regression analysis were used to conduct association
      analysis. RESULTS: TDT analysis confirmed that CA4 allele in CL/P and CPO groups
      preferentially transmitted to the affected offspring (P = 0.018, P = 0.041).
      Logistic regression analysis indicated that the recessive model of inheritance
      was supported, and CA4 itself or CA4 acting as a marker for a disease allele or
      haplotype was inherited in a recessive fashion (P = 0.009). CONCLUSIONS: MSX1
      gene is associated with NSCLP, and MSX1 gene may be directly involved either in
      the etiology of NSCLP or in linkage disequilibrium with disease-predisposing
      sites.

PMID- 18070438
TI  - [Porphyromonas gingivalis vesicle induced cellular inflammatory responses of
      gingival epithelial cells in vitro].
AB  - OBJECTIVE: To establish the model of cellular inflammatory responses of gingival
      epithelial cells in vitro induced by Porphyromonas gingivalis vesicle and to
      probe into the pathogenesis of Porphyromonas gingivalis in periodontitis.
      METHODS: The effect of Porphyromonas gingivalis vesicle on prostaglandin E(2)
      (PGE(2)) production of gingival epithelial cells was detected by ELISA and the
      effects of Porphyromonas gingivalis vesicle on cyclooxygenase-2 (COX-2),
      interleukin (IL)-6 and IL-8 mRNA expression in gingival epithelial cells were
      determined by Real-time reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: Porphyromonas gingivalis vesicle dose-dependently induced PGE(2)
      production and up-regulated COX-2, IL-6 and IL-8 mRNA expression in gingival
      epithelial cells significantly. CONCLUSIONS: Cellular inflammatory responses of
      gingival epithelial cells induced by Porphyromonas gingivalis vesicle may
      contribute to the initiation and progression of periodontitis.

PMID- 18070439
TI  - [Evaluation of midazolam intravenous sedated patient's comfort degree in
      mandibular third molar surgery].
AB  - OBJECTIVE: To evaluate the clinical efficacy and safety of continuous low-flow
      intravenous infusion of midazolam sedation in mandibular third molar surgery.
      METHODS: Fifty healthy patients with symmetrically placed impacted bilateral
      mandibular third molars were included in this self controlled, randomized
      clinical study. Degree of comfort (their actual current anxiety level) was
      assessed using a visual analogue scale (VAS) of pain and anxiety. Patients'
      satisfaction and degree of amnesia were also evaluated. Vital signs and oxygen
      saturation were recorded. RESULTS: Low dose midazolam sedation obviously
      increased the degree of patients' comfort and satisfaction. Vital signs and
      oxygen saturation levels did not differ significantly between the two groups.
      CONCLUSIONS: Midazolam as an intravenous sedation agent in mandibular third molar
      surgery showed satisfactory effect on patients with mild dental fear.

PMID- 18070440
TI  - [Clinical application of acellular dermal matrix to prevent gustatory sweating
      syndrome].
AB  - OBJECTIVE: To evaluate the clinical effect of acellular dermal matrix (ADM) on
      preventing Frey syndrome after parotidectomy. METHODS: Fifty-seven patients were
      randomized into two groups, ADM group (30 patients) receiving acellular dermal
      matrix and control group (27 patients) without application of acellular dermal
      matrix. The incidence of Frey syndrome was evaluated after operation. RESULTS:
      The incidences of Frey syndrome were 13.3% in ADM group and 55.6% in control
      group. There was significant difference in Frey syndrome incidence between the
      two groups (P < 0.01). CONCLUSIONS: The application of acellular dermal matrix
      could effectively prevent Frey syndrome after parotidectomy.

PMID- 18070441
TI  - [Structuring the Answerable Clinical Questions IV. Evidence searching for
      evidence-based dental practices].

PMID- 18070442
TI  - [Techniques of oral cavity photography V. The photography of oral maxillofacial
      surgery, part one].

PMID- 18070443
TI  - [Detection of chromosomal aberration in paraffin-embedded synovial sarcoma
      tissues by fluorescence in-situ hybridization].
AB  - OBJECTIVE: To evaluate the application of fluorescence in-situ hybridization
      (FISH) in detection of gene translocation in paraffin-embedded tissue samples of
      synovial sarcoma. METHODS: Interphase FISH was carried out in paraffin-embedded
      tissue of 42 cases of synovial sarcoma and 9 cases of non-synovial sarcoma, using
      a LSI SYT (18q11.2) dual color break-apart probe. In all of the cases studied,
      the gene fusion product SYT-SSX was also analyzed by reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: Positive signals were detected in 37
      cases (88.1%) of synovial sarcoma by FISH, as compared with 35 cases (83.8%) by
      RT-PCR and 39 cases (92.9%) by both techniques. Of the 39 positive cases, 33
      cases (78.5%) revealed SYT gene translocation. CONCLUSIONS: FISH may serve as an
      adjunctive diagnostic tool in problematic cases of synovial sarcoma and can be
      applied in paraffin-embedded tissue samples. As compared with RT-PCR, FISH is
      also sensitive and reliable. The methodology is less labor intensive and time
      consuming. FISH has great potential in molecular diagnosis of soft tissue tumors.

PMID- 18070444
TI  - [Analysis of 13q14 chromosomal instability in soft tissue tumors by fluorescence
      in-situ hybridization].
AB  - OBJECTIVE: To investigate the genetic status of 13q and its role in the
      oncogenesis and progress of soft tissue tumors. METHODS: Forty-one soft tissue
      tumors, including 9 benign tumors, 9 tumors of malignant potential and 23
      sarcomas, were studied by fluorescence in-situ hybridization (FISH) using dual
      color probes. The probes were generated from BAC clones RP11-685I15, RP11-352N7
      and RP11-505F3, corresponding to Rb, RFP2, KCNRG and KLF5 genes respectively.
      RESULTS: Loss of heterozygosity (LOH) of RP11-685I15 were found in 8/41 cases,
      LOH of RP11-352N7 was seen in 4/41 cases and LOH of RP11-505F3 was present in
      3/41 cases. LOH of all 3 loci were detected in 2 cases. LOH of RP11-61K9, an
      internal control locus, was detected in 2 cases. One case of malignant peripheral
      nerve sheath tumor showed amplification at all 3 loci. Amplification of RP11
      505F3 was seen in another 2 cases. CONCLUSIONS: A significant percentage of soft
      tissue tumors exhibited chromosomal instability, reflected by an increase of LOH
      at tumor-suppressing gene loci. The incidence of 13q abnormality was different in
      various types of soft tissue tumors, indicating that alterations of Rb, RFP2,
      KCNRG and KLF5 tumor suppressing genes may play diverse roles in different types
      of soft tissue tumor.

PMID- 18070445
TI  - [Sclerosing rhabdomyosarcoma: a clinicopathologic study of four cases with review
      of literature].
AB  - OBJECTIVE: To study the clinicopathologic characteristics of sclerosing
      rhabdomyosarcoma (SRMS) and its distinction from embryonal rhabdomyosarcoma
      (ERMS) and alveolar rhabdomyosarcoma (ARMS). METHODS: The clinical, histologic
      and immunohistochemical features of 4 cases of SRMS were studied. The literature
      was reviewed. RESULTS: All the 4 cases occurred in adults. The age of patients
      ranged from 20 to 54 years (mean = 41.5 years). The male-to-female ratio was 1:1.
      The tumor was located in the left wrist, right thigh, right face and right cheek
      respectively and the tumor size varied from 2.5 cm to 10 cm in dimension (mean =
      5.7 cm). Histologically, SRMS was characterized by the presence of large amounts
      of heavily hyalinized matrix, mimicking osteoid or chondroid tissue. The tumor
      cells were composed predominantly of primitive small round cells which were
      arranged in diverse growth patterns, including fascicular, cord-like, single
      file, trabecular, microalveolar and pseudovascular structures. A few
      rhabdomyoblasts were identified in 1 case. A second spindle cell component was
      focally found in 2 cases, resembling spindle cell rhabdomyosarcoma or peripheral
      nerve sheath tumor. Immunohistochemically, all cases showed diffuse staining for
      Myo D1 and focal staining for desmin. The staining for myogenin was often
      negative. Three of the cases also expressed muscle-specific actin and 2 cases
      were positive for alpha-smooth muscle actin. They were all negative for h
      caldesmon, S-100 protein, CD31, CD34, AE1/AE3 and anaplastic lymphoma kinase
      protein. CONCLUSIONS: SRMS differs from ERMS and ARMS morphologically. Recent
      cytogenetic studies however suggest a histogenetic relationship with ERMS.
      Familiarity with its morphologic features and immunophenotype may help to
      distinguish this peculiar variant of rhabdomyosarcoma from a variety of lesions
      with abundant sclerosing matrix.

PMID- 18070446
TI  - [Fibrous dysplasia: molecular clonality analysis of 21 cases].
AB  - OBJECTIVE: To investigate the neoplastic nature of fibrous dysplasia by molecular
      clonality approaches. METHODS: Twenty-one cases of fibrous dysplasia were
      examined by clonality assays based on X-chromosomal inactivation mosiacism.
      Lesional and non-lesional tissues were microdissected from paraffin sections
      followed by DNA extraction. The DNA was predigested by HpaII or HhaI, and then
      amplified by nested PCR targeting phosphoglycerate kinase (PGK) and androgen
      receptor (AR) genes. Single nucleotide polymorphism (SNP) at the PGK locus was
      identified by incubation of the PCR products with Bst XI and agarose gel
      electrophoresis, and CAG repeat length polymorphism at AR locus was determined by
      denaturing polyacrylamide gel electrophoresis and visualized by silver staining.
      RESULTS: Microscopically, all 21 cases showed characteristic features of fibrous
      dysplasia, including spindle fibrous cell proliferation and immature bone
      trabeculae at various proportions. DNA polymorphisms at AR locus and SNP of PGK
      gene were found in 15 of 21, and 4 of 21 cases, respectively. All 19 cases were
      monoclonal in nature. Two cases showed no polymorphism at either AR or PGK gene
      locus. CONCLUSIONS: Fibrous dysplasia is likely a clonal, neoplastic process.
      Additional studies of larger number of cases are needed for a definitive
      conclusion.

PMID- 18070447
TI  - [Expression of membrane/soluble MHC class I chain-related molecule A and NKG2D
      receptor in osteosarcoma and its clinical significance].
AB  - OBJECTIVE: To study the expression of membrane MICA (mMICA), soluble MICA (sMICA)
      and NKG2D receptor in cases of osteosarcoma and to analyze its clinical
      significance. METHODS: Expression of mMICA in osteosarcoma tissue of 43 cases was
      detected with immunohistochemistry. Expression of NKG2D in peripheral blood
      lymphocytes of 16 cases was analyzed by flow cytometry. Serum level of soluble
      MICA (sMICA) was measured by ELISA. RESULTS: mMICA was widely expressed in
      osteosarcoma tissue (37/43). Expression of NKG2D in peripheral blood lymphocytes
      was significantly decreased. High levels of mMICA and NKG2D expression were
      associated with better differentiation and earlier tumor stage of osteosarcoma (P
      < 0.05). A significant increase in serum level of sMICA was demonstrated in
      patients with metastasis and advanced tumor. CONCLUSIONS: The mMICA expression in
      tumor tissue, NKG2D expression in peripheral lymphocytes and serum sMICA level
      correlate with the differentiation and stage of osteosarcoma. These parameters
      may thus represent potential diagnostic and prognostic markers in patients with
      osteosarcoma. Manipulation of the MICA-NKG2D pathway may become a target of
      immunotherapy for osteosarcoma.

PMID- 18070448
TI  - [Detection of t (14; 18) chromosomal translocation in paraffin-embedded tissues
      of follicular lymphoma and its clinical significance].
AB  - OBJECTIVE: To study the genetic aberrations and their pathologic significance in
      follicular lymphoma (FL). METHODS: Paraffin-embedded tissue samples of 55 cases
      of FL, 28 cases of other small B-cell lymphomas and 10 cases of reactive
      follicular hyperplasia were retrieved. Nested polymerase chain reaction (PCR) was
      used to detect clonal rearrangement of immunoglobulin heavy chain gene (IgH) in
      FL and other small B-cell lymphomas. The translocation t (14; 18) was studied by
      PCR and dual-color fluorescence in-situ hybridization (FISH) in FL. Cases of
      reactive follicular hyperplasia were used as controls. RESULTS: Amongst the 55
      cases studied, 49 cases were nodal and 6 cases were extranodal. There were 33
      males and 22 females. The male-to-female ratio was 1.5:1. The median age of the
      patients was 57 years. Twenty-five cases belonged to histologic grade 1, while 19
      cases were grade 2 and 11 cases were grade 3. Beta-actin DNA was detected in 50
      cases of FL. Amongst those 50 cases, clonal IgH rearrangement was present in 34
      (68%). Twenty-four cases (48%) and 25 cases (50%) were positive for FR3A and FR2
      respectively. Fifteen cases (30%) showed dual positivity for both FR3A and FR2.
      Thirty-four cases (68%) demonstrated clonal IgH rearrangement. As for other small
      B-cell lymphomas, 25 cases were positive for beta-actin. FR3A and FR2 were
      detected in 18 and 17 cases respectively. Clonal IgH rearrangement was
      demonstrated in 24 cases. In contrast, none of the 4 cases of reactive follicular
      hyperplasia showed the clonal rearrangement pattern. Amongst the 44 cases of
      nodal FL analyzed, t (14; 18) was detected in 15 cases (with 14 cases in MBR and
      1 case in mcr). In general, FISH was superior to PCR in detecting t (14; 18)
      using paraffin-embedded tissue samples. CONCLUSIONS: The detection rate of clonal
      IgH rearrangement in FL is lower than that in other small B-cell lymphomas.
      Demonstration of t (14; 18) in paraffin-embedded tissue samples by FISH helps in
      diagnosis of FL. FISH is superior to PCR, as the technique is more sensitive and
      less labor intensive.

PMID- 18070449
TI  - [Inflammatory myofibroblastic tumor of bladder: a clinicopathologic study of five
      cases].
AB  - OBJECTIVE: To study the clinicopathologic features, diagnosis and differential
      diagnosis of inflammatory myofibroblastic tumor of the urinary bladder. METHODS:
      Excisional specimens from 5 cases of vesical inflammatory myofibroblastic tumor
      were studied by light microscopy and immunohistochemistry (EnVision). The
      clinical data were also analyzed. RESULTS: Among the 5 patients studied, 3 were
      males and 2 were females. The age of the patients ranged from 10 to 53 years
      (mean age = 35 years). The most common clinical presentation was micturition pain
      and hematuria. Three cases were located at the dome of the urinary bladder and
      the remaining 2 cases were found in the left lateral wall. Histologically, the
      tumor varied from myxoid to highly cellular. The tumor cells were spindle to
      stellate in shape, widely separated or showed a compact fascicular pattern. There
      were often associated with mixed inflammatory infiltrates and an irregular
      meshwork of small dilated vessels. Immunohistochemical study showed that the
      tumor cells expressed AE1/AE3 (5/5), vimentin (5/5), smooth muscle actin (5/5),
      calponin (5/5), caldesmon (3/5), desmin (4/5) and anaplastic lymphoma kinase
      protein (4/5). Follow-up data were available in 4 patients and none had local
      recurrence or died of this disease. CONCLUSION: Inflammatory myofibroblastic
      tumour of urinary bladder is a rarely encountered but distinctive neoplasm with
      intermediate malignant potential.

PMID- 18070450
TI  - [Effect of nordy on biological behaviors of malignant glioma cell line U87MG and
      the analysis of differential expression proteome].
AB  - OBJECTIVE: To explore effects of nordy on biological behaviors of human malignant
      glioblastoma cell line U87MG in vitro and transplanted tumor in vivo, and to
      identify the differential proteome upon Nordy induced differentiation. METHODS:
      Glioblastoma U87MG cells were induced to differentiate by synthetic lipoxygenase
      inhibitor, Nordy. The drug was also given via peritoneal injection to nude mice
      (27 mg/kg body weight) bearing orthotopic transplanted tumors of U87MG cells in
      the brain. The tumor volumes and GFAP expression were measured. Total proteins of
      U87MG cells after Nordy treatment were analysed by two-dimensional gel
      electrophoresis. PDQuest 7.1 computer software was used to compare protein
      profiles of the treated cells with that of untreated control. Differentially
      expressed proteins were then selected and characterized by matrix assisted laser
      desorption ionization-time of flight-mass spectrometry. The functional aspects of
      these proteins were analyzed by bioinformatics. RESULTS: Nordy suppressed both
      the proliferation of U87MG cells in vitro and the tumor growth of orthotopic
      transplanted tumors in vivo (P < 0.01). The differentially expressed proteins
      induced by Nordy included proliferation-associated gene A, alternative splicing
      factor ASF-3, eukaryotic translation initiation factor 5A, coffilin 1 (non
      muscle), beta galactoside binding lectin, glyceraldehyde-3-phosphate
      dehydrogenase, enolase 1 and an unknown protein. CONCLUSIONS: Nordy promotes the
      differentiation of glioblastoma cells, by which it may serve as a therapeutic
      agent. Various proteins identified during Nordy-induced differentiation are
      involved in the cell proliferation, metabolism, differentiation, apoptosis and
      gene transcription.

PMID- 18070451
TI  - [Effect of Hydralazine on demethylation status and expression of APC gene,
      proliferation and apoptosis of human cervical cancer cell lines].
AB  - OBJECTIVE: To investigate the correlation between methylation status and gene
      expression of APC (adenomatous polyposis coli) gene in HeLa, CaSki and SiHa cell
      lines of cervical carcinoma, and explore the effect of hydralazine on the
      transcription regulation of the 5'CpG island demethylation of APC gene and the
      proliferation and apoptosis of the cell lines. METHODS: Methylation status and
      the expression of APC gene were analyzed using methylated specific PCR, RT-PCR
      and FQ-PCR methods. The expression of beta-catenin protein which correlates
      closely with APC was detected by SP method after treatment with Hydralazine. MTT
      and FCM assays were used to observe the changes of proliferation activity and
      apoptosis of the cells after Hydralazine treatment. RESULTS: (1) APC gene was
      methylated or hemimethylated respectively in HeLa and CaSki cell lines, at the
      same time, APC gene was not methylated in SiHa cell. (2) After having been
      treated by 40 micromol/L Hydralazine for 72 hours, growth inhibitory ratios of
      HeLa, CaSki and SiHa cell lines were (52.12 +/- 3.78)%, (44.31 +/- 2.59)% and
      (47.73 +/- 4.73)% respectively, on the contrary, normal cell HECV's growth
      inhibitory ratio was only (27.18 +/- 0.79)%. APC gene in HeLa and CaSki cell
      lines which were treated by 40 micromol/L Hydralazine for 72 hours was
      demethylated and expressed positively, the expression of APC mRNA in HeLa, CaSki
      and SiHa cell lines increased to 10.35, 11.40 and 0.73 times respectively. (3)
      Hydralazine, when used at the concentration of 40 micromol/L for 72 hours,
      induced S phase and G2/M phase arrest and apoptosis in HeLa and CaSki cells. beta
      catenin protein can be expressed in cell membrane after treatment with
      Hydralazine. CONCLUSION: APC gene methylation plays an important role in the
      carcinogenesis of cervical cells and can re-express after the treatment with
      Hydralazine which also could inhibit the growth of the cervical cancer cells.

PMID- 18070452
TI  - [Fine needle aspiration cytology of myxoid lesions of soft tissues: a study of 24
      cases].
AB  - OBJECTIVE: To summarize the diagnostic features of fine needle aspiration
      cytology (FNAC) of myxoid lesions in soft tissue, and to define the cytological
      criteria for differentiating benign lesions from sarcomas and between various
      myxoid lesions. METHODS: FNAC data of 24 soft tissue myxoid lesions (14 benign
      lesions, 10 malignant lesions) from 1993 to 2006 from Kiang Wu Hospital, Macau
      were reviewed in correlation with the clinical course or the results of biopsy.
      RESULTS: Ganglion, myxoma, and myxoid nodular fasciitis were the most common
      benign myxoid lesions of the soft tissues, all of which had low cellularity and
      lack of marked cellular atypia in smears in common. Ganglion was characterized by
      the disappearance of or the gradual minimization of the nodule after aspiration
      and the lack of blood vessel in smears. Myxoid nodular fasciitis was
      characterized by a pleomorphic pattern of proliferative cells and the presence of
      ganglion cell-like cells. Myxoid liposarcoma, extraskeletal myxoid chondrosarcoma
      and myxofibrosarcoma were the most common myxoid sarcomas. Cytologically, they
      had high cellularity and various degrees of cellular atypia. Myxoid liposarcoma
      exhibited branching chicken-wire like capillary vessels and/or lipoblasts;
      myxofibrosarcoma were prominent in both pleomorphic and atypia of the cells. The
      data revealed that the diagnostic accuracy of FNAC was nearly 100% in
      differentiating benign and malignant myxoid lesions of the soft tissues. The
      coordinate rate to the histopathology diagnosis of the common myxoid lesions of
      the soft tissues was above 75% (benign 71.4% and malignancy 80% respectively).
      CONCLUSIONS: FNAC is an effective method in diagnosing myxoid lesions of soft
      tissue, in correlation with the clinical data and the accessory examinations.
      FNAC can provide an objective basis for the treatment of myxoid lesions and
      prevention of unnecessary surgical operations.

PMID- 18070453
TI  - [Preparation of holing machine and receptor paraffin blocks for tissue array].

PMID- 18070454
TI  - [Analysis of mutations in IgVH genes in diffuse large B-cell lymphomas].

PMID- 18070455
TI  - [Role of heat shock protein 47 on experimental diabetic nephropathy of rats].

PMID- 18070456
TI  - [Notch signaling proteins and oncogenesis].

PMID- 18070457
TI  - [Advances in anti-beta antibody treatment of Alzheimer's disease].

PMID- 18070458
TI  - [Diagnosis and substaging of pT1 bladder cancer].

PMID- 18070459
TI  - [Malignant epithelioid angiomyolipoma of the kidney: report of a case].

PMID- 18070460
TI  - [CD30-positive of diffuse large B-cell lymphoma of small intestine co-existing
      with tubular adenocarcinoma of rectum: report of a case].

PMID- 18070461
TI  - [Microglandular adenosis of breast: report of a case].

PMID- 18070465
TI  - [Reasonable application of percutaneous coronary intervention].

PMID- 18070462
TI  - [Medulloblastoma with extensive nodularities: report of a case].

PMID- 18070466
TI  - [The antiplatelet effect of clopidogrel is not attenuated by statin treatment in
      patients with acute coronary syndromes undergone coronary stenting].
AB  - OBJECTIVE: To evaluate the interaction of atorvastatin or pravastatin with
      clopidogrel on platelet activation and aggregation function in patients with
      acute coronary syndromes (ACS) undergoing coronary stenting. METHODS: Between
      April and December 2006, a total of 150 hospitalized ACS patients undergoing
      coronary stenting were randomized to receive atorvastatin (n = 50), pravastatin
      (n = 50) or no statin (n = 50) one day post procedure. All patients received
      standard antiplatelet treatment including aspirin 300 mg/d and loading dose 300
      mg of clopidogrel followed by maintenance dose 75 mg/d. The expressions of CD62P
      and PAC-1 and the maximal platelet aggregation rate (MPAR) induced by 20
      micromol/L ADP were measured at day 1 before statin therapy (baseline) and day 3
      after procedure. RESULTS: Baseline clinical characteristics and levels of CD62P,
      PAC-1 and MPAR at the baseline were comparable among three groups. After 3-day
      statin treatment, the changes of CD62P [(4.69 +/- 16.78)% vs. (1.35 +/- 10.86)%
      vs. (2.97 +/- 10.21)%], PAC-1 [(12.78 +/- 22.07)% vs. (8.01 +/- 21.23)% vs.
      (10.65 +/- 21.39)%] and MPAR [(5.44 +/- 18.68)% vs. (7.15 +/- 19.59)% vs. (3.76
      +/- 23.42)%] among three groups were not significantly different (all P > 0.05).
      Subgroup analysis showed that DeltaCD62P [(7.50 +/- 19.35)% vs. (3.24 +/- 11.18)%
      vs. (2.53 +/- 8.87)%], DeltaPAC-1 [(13.40 +/- 24.62)% vs. (11.28 +/- 19.90)% vs.
      (10.11 +/- 21.29)%] and DeltaMPAR [(7.56 +/- 19.11)% vs. (7.87 +/- 23.60)% vs.
      (6.75 +/- 23.30)%] in ACS patients were also similar among three groups (all P >
      0.05). CONCLUSION: Neither atorvastatin nor pravastatin attenuates the
      antiplatelet function of clopidogrel in ACS patients early post coronary
      stenting.

PMID- 18070468
TI  - [Effects of intensive antiplatelet therapy in patients with high platelet
      aggregability after percutaneous coronary intervention].
AB  - OBJECTIVE: Post percutaneous coronary intervention (PCI) major cardiac event rate
      is high in patients with high platelet aggregability. We observed the effects of
      intensive antiplatelet therapy in these patients. METHODS: ADP-induced platelet
      inhibition rates were less than 30% after 24 h treatment with Clopidogrel (300
      mg) in 402 patients out of 1556 patients who underwent PCI in our institute
      between January 2004 to June 2006. These patients were randomly divided into
      control group (Clopidogrel 75 mg/d and aspirin 100 mg/d, n = 201) or treatment
      group (Clopidogrel 75 mg/d and aspirin 100 mg/d plus cilostazol 200 mg/d, n =
      201). Major adverse cardiac events were analyzed after 6 months treatments.
      RESULTS: Patients with ADP-induced platelet inhibition rates < 30% were
      significantly lower in treatment group compared to control group after 28 days
      treatments (9.4% vs. 89.6%, P < 0.05). Thrombosis complication (0.5% vs. 3.0%),
      death (0 vs. 1.0%), non-fatal myocardial infarction (0.5% vs. 1.5%), hemorrhagic
      (6% vs. 4%) rates were similar between treatment and control group while target
      vessel revascularization rate was significantly lower in treatment group compared
      to control group (6.5% vs. 15.9%, P < 0.05). Total MACE rate was therefore
      significantly lower in treatment group than that in control group (13.5% vs.
      25.4%, P < 0.05). CONCLUSION: Intensive anti-platelet treatment could
      significantly reduce major cardiac event rates in patients with high platelet
      aggregability after percutaneous coronary intervention.

PMID- 18070469
TI  - [Prevalence and risk factors of atrial tachyarrhythmia before and after
      percutaneous closure of secundum atrial septal defect in patients over 40 years
      of age].
AB  - OBJECTIVE: In this study, we attempted to observe the prevalence and risk factors
      of atrial tachyarrhythmias (AT) before and after transcatheter closure of atrial
      septal defect (ASD). METHODS: 264 adult patients aged over 40 years (67 men and
      197 women) who underwent transcatheter closure of ASD between September, 1997 and
      December, 2005 were included in this study. Incidence of preoperative and
      postoperative AT was analyzed, risk factors for AT were determined with
      multivariate stepwise logistic regression analysis. RESULTS: Incidence of AT
      before closure was 9.1% (24/264). Twenty-nine patients (11.0 percent) developed
      AT after transcatheter closure (24 atrial fibrillation, 1 paroxysmal flutter, 4
      paroxysmal atrial arrhythmia). The prevalence in patients of 40 to 49 years, 50
      to 59 years and above 60 years was 4.3%, 14.6% and 26.3%, respectively. Most
      patients with atrial fibrillation were symptomatic. Compared to patients without
      AT, patients developed AT after closure were significantly older (53.0 +/- 7.6
      years vs. 47.8 +/- 6.6 years, P < 0.01) and had larger defects (23.5 +/- 5.7 mm
      vs. 21.3 +/- 5.2 mm, P > 0.05), higher systolic pulmonary pressure (38.4 +/- 13.1
      vs. 34.1 +/- 10.1, P < 0.05), larger left atrium dimension [(38.0 +/- 3.9) mm Hg
      (1 mm Hg = 0.133 kPa) vs. (33.6 +/- 4.4) mm Hg, P < 0.01], larger end diastolic
      right ventricular dimension [(34.7 +/- 5.9) mm vs. (32.1 +/- 6.8) mm, P > 0.05],
      higher incidence of tricuspid regurgitation (96.6% vs. 75.3%, P = 0.01), higher
      incidence of preoperative AT (51.7% vs. 3.8%, P < 0.01) and higher incidence of
      hypertension (27.6% vs. 10.2%, P = 0.013). Multivariate analysis showed that
      older age [odds ratio (OR) 2.659, 95 percent confidence interval (CI) 1.080 to
      6.547, P < 0.05], presence of preoperative AT (OR 54.311, CI 9.819 to 300.395, P
      < 0.01), and left atrial enlargement (OR 8.529 per 10 mm increment, CI 2.162 to
      33.643, P < 0.01) were independent predictors of AT after closure. CONCLUSIONS:
      Incidence of AT was similar before and after percutaneous closure in patients
      with atrial septal defects aged 40 years and over. The risk of AT is related to
      the age at the time of transcatheter closure, the presence of preoperative AT and
      enlarged left atria.

PMID- 18070470
TI  - [Bone marrow mesenchymal stem cell transplantation aggravates postangioplasty
      aortic restenosis in rats].
AB  - OBJECTIVE: To observe the effect of bone marrow mesenchymal stem cell
      transplantation on postangioplasty aortic restenosis in rats. METHODS: 48 SD rats
      were randomly divided into normal control group, balloon injury group, balloon
      injury and MSCs transplantation group. MSCs were pre-labeled by DAPI (25
      microg/ml) and then infused into aorta through the balloon catheter (MSCs 2 x
      10(6)/animal). Thoracic aorta were taken for histological examination (frozen and
      paraffin sections) at 1, 2, 6 weeks post angioplasty, respectively. DAPI labeled
      MSCs were detected under immunofluorescence microscopy. Expressions of c-kit,
      proliferating cell nuclear antigen (PCNA), smooth muscle alpha-actin (alpha-SMA)
      in aorta were determined by immunocytochemistry using related antibodies.
      RESULTS: The DAPI-labeled MSCs could be detected on impaired intimae and alpha
      SMA expression was seen in these cells 1 weeks after MSCs transplantation.
      Similar weak c-kit expression in neointima was found in both injury and
      transplantation group at 2 weeks (P > 0.05). Expressions of PCNA and alpha-SMA in
      the neointima were significantly higher in transplantation group than in injury
      group at 2 weeks. Intima/tunica media area ratio and luminal stenosis ratio were
      significantly increased in transplantation group than injury group at 6 weeks
      (all P < 0.05). CONCLUSION: Bone marrow MSCs transplanted post aortic angioplasty
      could home to serious wounded aortic intima, differentiate into smooth muscle
      like cells, promote neointima cellular proliferation and aggravate
      postangioplasty aortic restenosis in rats.

PMID- 18070472
TI  - [Retrospective survey on clinical characteristics and therapy management for
      hospitalized patients with essential hypertension in Beijing].
AB  - OBJECTIVE: To evaluate the clinical characteristics and therapy conditions in
      hospitalized patients with essential hypertension in Beijing. METHODS: Patients
      with essential hypertension hospitalized in 20 Beijing hospitals in recent 2
      years were included in this epidemiologic retrospective survey. Data on age,
      blood pressure level, risk factors and complicated diseases, antihypertensive
      medication and heart structural and functional characteristics measured by
      echocardiography were collected. RESULTS: Total 5106 hospitalized patients (mean
      age 63.78 years) with essential hypertension were recorded. Mean blood pressure
      was 145.97/84.23 mm Hg (1 mm Hg = 0.133 kPa). Among them, 75.5% complicated with
      at least one risk factor, 30% suffered from heart failure. The atria enlargement
      and left ventricular diastolic dysfunction were the two most common
      echocardiographic pathological changes. Left ventricular hypertrophy is
      positively correlated with blood pressure. Logistic regression analysis showed
      that increased systolic blood pressure, diastolic blood pressure and plasma
      creatinine, old age and decreased HDL-cholesterol were risk factors of left
      ventricular hypertrophy. Only 32.1% patients achieved the goal blood pressure
      level (<140/90 mm Hg) and 38.1% patients were treated with monotherapy. The most
      commonly used antihypertensive drugs were calcium channel blockers and diuretics.
      CONCLUSIONS: It is of importance to strictly follow the therapy guidelines on
      hypertension treatment and use combined drug therapy to increase the rate of
      patients reaching goal blood pressure level and reduce hypertensive
      complications.

PMID- 18070473
TI  - [Diagnostic value of ischemia-modified albumin in patients with acute coronary
      syndrome].
AB  - OBJECTIVE: To investigate the diagnostic value of ischemia-modified albumin (IMA)
      for patients with acute coronary syndrome (ACS). METHODS: We detected the IMA
      levels by albumin cobalt-binding (ACB) test and observed its dynamic changes in
      492 patients with ACS, 74 patients with high blood pressure, 78 patients with
      viral myocarditis (VMC), 395 patients with acute chest pain (133 patients with
      acute ACS and 262 follow-up patients due to chest pain), 68 patients underwent
      percutaneous coronary intervention (PCI) and 830 healthy controls. Cardiac
      troponin I (cTnI) levels were assayed and electrocardiogram (ECG) recorded in
      patients with ACS. RESULTS: The optimal diagnostic cutoff point for IMA in this
      study population was found to be 0.45 ABSU by ROC analysis. The IMA level (ABSU)
      in ACS group (0.55 +/- 0.11) was significantly higher than that in VMC group
      (0.38 +/- 0.11) and IMA levels in ACS and VMC groups were both higher than that
      in control and high blood pressure groups (0.34 +/- 0.08 and 0.35 +/- 0.08, all P
      < 0.05). IMA levels and the positive rates in patients with ACS were
      significantly higher (0.54 +/- 0.12 vs 0.44 +/- 0.12, 77.4% vs 39.3%, all P <
      0.01) than those in chest pain follow-up group. In 133 patients with ACS,
      positive rate for IMA was significantly higher than that for cTnI within 1 h of
      admission (82.0% vs 40.6%, P < 0.01), and was similar at 6 - 24 h after admission
      (96.2% vs. 95.5%, P > 0.05). In 72 patients presenting to the emergency center
      within 3 h of acute chest pain and with negative cTnI, positive rate for IMA was
      86.1% and for ECG 72.2%, the sensitivity for ACS diagnosis rised to 93.1% with
      both methods. The IMA leve was higher immediately after PCI than that before PCI
      (P < 0.05). IMA levels peaked 1d after hospitalization, then decreased gradually
      and returned to normal 14 days later. CONCLUSIONS: IMA was a useful biochemical
      marker for the early diagnosis of ACS.

PMID- 18070474
TI  - [T-lymphocyte voltage dependent K(+) channel is upregulated in patients with
      acute coronary syndrome].
AB  - OBJECTIVE: To determine current density of voltage-gated potassium channels and
      Kv1.3 express in T-lymphocyte derived from patients with acute coronary syndrome
      (ACS). METHODS: Peripheral blood mononuclear cells were collected from 12
      patients with ACS and 10 control donors. Whole-cell patch clamp technique was
      used to record the outward K(+) currents (IK) and western blots technique was
      used to detect the express of Kv1.3 protein in lymphocyte. RESULTS: (1) The
      current density of voltage-gated potassium channel was significantly higher in
      ACS patients [(269 +/- 94) pA/pF] than in controls [(191 +/- 64) pA/pF, P < 0.01]
      while membrane capacitance was similar between the two groups. (2) Kv1.3 protein
      expression was also significantly increased in ACS patients than in controls (P <
      0.01). CONCLUSION: The lymphocyte voltage-gated potassium channel is upregulated
      in patients with ACS suggesting a role of Kv activation in the pathophysiology of
      ACS.

PMID- 18070478
TI  - [A case report in a patient with hyperkalemia inducing ischemic upright T wave].

PMID- 18070475
TI  - [Chronic effects on the prevention of atrial fibrillation recurrence in patients
      with lone paroxysmal atrial fibrillation treated with amiodarone, segmental
      pulmonary vein ablation, or amiodarone plus losartan: a prospective cohort
      study].
AB  - OBJECTIVE: This study was designed to compare clinical efficacy of segmental
      pulmonary vein ablation (SPVI), amiodarone or amiodarone plus losartan on sinus
      rhythm maintenance in patients with lone paroxysmal atrial fibrillation (PAF).
      METHODS: Patients with lone PAF were treated with amiodarone alone (A, n = 52),
      segmental pulmonary vein isolation (SPVI, n = 51), or amiodarone plus losartan
      (AL, n = 51). The primary endpoint of this study was the incidence of symptomatic
      atrial tachyarrhythmia (> 30 s) documented by 12 lead ECG or Holter during 12
      months follow-up period. RESULTS: During follow-up, AF was documented in 24
      patients (46.2%) in A group, 11 patients (21.6%) in SPVI group and 12 (23.5%) in
      AL group (P < 0.05 vs. A group). The Kaplan-Meier survival analysis demonstrated
      a significant equally reduction in AF recurrence in SPVI and AL groups (P =
      0.009, log-rank test and P = 0.018, log-rank test, respectively) compared with A
      group. The hazard ratio for AF recurrence in patients treated with SPVI and
      amiodarone plus losartan was 0.41 (95% CI 0.200 to 0.848, P = 0.016) and 0.46
      (95% CI 0.225 to 0.953, P = 0.036), respectively. Incidences of major adverse
      cardiac events were similar among the groups (9.6% in A, 3.9% in SPVI and 7.8% in
      AL group, P > 0.05). CONCLUSION: The results of this study suggest that the
      segmental pulmonary vein isolation and amiodarone plus losartan are superior to
      amiodarone alone for preventing AF recurrence in patients with lone PAF.

PMID- 18070479
TI  - [Effect of retinoid X receptor activation on oxidized low-density lipoprotein
      induced cell differentiation of murine macrophage cell line into dendritic like
      cells].
AB  - OBJECTIVE: To investigate the effect and related mechanism of retinoid X receptor
      (RXR) activation on oxidized low-density lipoprotein (ox-LDL) induced
      differentiation of macrophage into dendritic cell. METHODS: RAW264.7 murine
      macrophage cell line was cultured with ox-LDL for 48 h in the absence and
      presence of RXR activator 9-cisRA or SR11237. Cell morphology was observed by
      phase contrast microscope and cell surface markers involved in dendritic cell
      immune maturation and activation was analyzed by FACS. Cellular reactive oxygen
      species production was detected by CM-H2DCFDA fluorescent probe. RESULTS: ox-LDL
      treated RAW264.7 murine macrophage cell line differentiated into dendritic like
      cells after 48 h and cell surface markers CD40, CD86, CD83, MHC Class II and CD1d
      were upregulated. These changes could be attenuated by cotreatment with 9-cisRA
      or SR11237. Upregulated cell surface markers CD40, CD86, CD83, MHC Class II and
      CD1d by ox-LDL were decreased about 47%, 43%, 48%, 32% and 17% respectively by 9
      cisRA and 38%, 38%, 46%, 36% and 32% respectively by SR11237. The effect of 9
      cisRA and SR11237 was dose dependent. Cellular reactive oxygen species were
      significantly increased in ox-LDL-treated RAW264.7 cells (MFI 38.24 +/- 4.20 vs.
      4.46 +/- 0.39, P < 0.05) and which was significantly reduced by 9-cisRA (10(-7)
      mol/L) and SR11237 (10(-6) mol/L) to 12.60 +/- 1.52 and 17.89 +/- 1.91
      respectively (all P < 0.05). CONCLUSION: RXR activation partly inhibits the
      differentiation of ox-LDL induced macrophage into dendritic cell by reducing
      oxidative stress injury.

PMID- 18070480
TI  - [In vitro MR imaging of Fe(2)O(3)-PLL labelled rabbit peripheral blood
      endothelial progenitor cells].
AB  - OBJECTIVE: To perform in vitro magnetic resonance imaging on magnetic iron oxide
      (Fe(2)O(3)-PLL) labeled rabbit peripheral blood endothelial progenitor cells
      (EPCs). METHODS: Fe(2)O(3) was incubated with PLL for 2 hours to form Fe(2)O(3)
      PLL. Rabbit peripheral blood mononuclear cells (MNCs) were isolated and EPCs were
      selected by adherence method, expanded and incubated with Fe(2)O(3)-PLL.
      Intracellular iron was detected by Prussian blue stain and under electron
      microscope. MTT assay was used to evaluate cell survival and proliferation of
      Fe(2)O(3)-PLL labeled EPCs. Flow cytometry was used to analysis cell cycle and
      apoptosis. The cells underwent in vitro MR imaging with various sequences.
      RESULTS: Iron-containing intracytoplasmatic vesicles could be observed clearly
      with Prussian blue staining and electron microscope observation. Survival, life
      cycle and apoptosis values obtained by MTT and flow cytometry analysis were
      similar among unlabelled EPCs and EPCs labeled with various concentrations
      Fe(2)O(3)-PLL. The signal intensity on MRI was significantly decreased in labeled
      cells compared with that in unlabeled cells. The percentage change in signal
      intensity (DeltaSI) was most significant on T(2)*WI and DeltaSI was significantly
      lower in cells labeled for 7 days than that labeled for 1 day. CONCLUSIONS: The
      rabbit peripheral blood EPCs can be labeled with Fe(2)O(3)-PLL without
      significant change in viability and proliferation. The labeled EPCs can be imaged
      with standard 1.5 T MR equipment. The degree of MR signal decreasing may
      indirectly reflect the cells count, growth state and division.

PMID- 18070481
TI  - [Intra-arterial transfusion of endothelial progenitor cells accelerate
      reendothelialization in balloon-denuded rabbit carotid arteries].
AB  - OBJECTIVE: To investigate the effects of endothelial progenitor cells (EPCs)
      transfusion on reendothelialization and neointima proliferation in balloon
      denuded rabbit carotid arteries. METHOD: Bone marrow-derived rabbit mononuclear
      cells (MNCs) were cultured in endothelial basal medium to form EPCs. The cell
      makers were assayed by immunocytochemistry. The rabbit right carotid artery was
      injured with 2.5 FPTCA balloon catheter and the EPCs (5 ml) were transfused into
      the injured carotid artery at a rate of 15 ml/h. The rabbits were killed at 7
      days or 14 days post operation. Reendothelialization area and ratio of
      intima/media (I/M) in injured artery were measured. RESULT: EPCs transfusion
      significantly increased the percentage of endothelialization at 7 days (50.923%
      +/- 2.476% vs. 28.647% +/- 2.241%) and at 14 days (82.609% +/- 2.611% vs. 49.800%
      +/- 2.660%) compared to control group (all P < 0.05). I/M ratio was significantly
      lower in EPCs transfusion group than that in control group (0.378 +/- 0.029 vs.
      0.898 +/- 0.038, P < 0.05) 14 days after operation. The labeled EPCs could be
      detected by immunohistochemistry in the injured vessel wall. CONCLUSION: Intra
      arterial transfusion of EPCs can effectively accelerate reendothelialization and
      reduce neointima formation in balloon-denuded rabbit carotid arteries.

PMID- 18070482
TI  - [Effects of adrenomedullin on angiotensin II-induced collagen synthesis in
      vascular adventitial fibroblasts].
AB  - OBJECTIVE: To explore the effects of adrenomedullin (ADM) on Angiotensin II
      (AngII)-induced collagen synthesis in cultured rat vascular adventitial
      fibroblasts. METHODS: Rat vascular adventitial fibroblasts were cultured in
      vitro. ADM produced and secreted from adventitia in the presence of AngII was
      detected by radioimmunoassay, type I, III collagen contents in adventitia
      fibroblasts were measured by ELISA and the expressions of TGFbeta1 and MMP-2 were
      determined by RT-PCR and Western blotting. RESULTS: AngII significantly induced
      ADM secretion in adventitial fibroblasts in a dose-dependent manner. These
      effects could be reduced by 45%, 3% and 46%, through pre-treatment with Losartan,
      PD123319 or both, respectively for 30 min in culture medium. The AngII-induced
      type I, III collagen secretion in adventitial fibroblasts was significantly
      reduced by AMD in a dose-dependent manner, (P < 0.01) while ADM agonist ADM(22 -
      52) significantly potentiated the effect of AngII; ADM also reduced AngII-induced
      expression of TGFbeta1 at mRNA and protein levels in a dose-dependent manner.
      AngII reduced the expression of MMP-2 at mRNA and protein levels in adventitial
      fibroblasts and these effects could be reversed by AMD (10(-8) mol/L).
      CONCLUSION: AngII stimulated ADM secretion in adventitia fibroblasts, ADM in turn
      can inhibit AngII-induced type I, III collagen synthesis in adventitial
      fibroblasts probably by downregulating the TGFbeta1 expression and upregulating
      MMP-2 expression. ADM therefore served as an antifibrotic factor in vascular
      remodeling process.

PMID- 18070483
TI  - [Association between myocardial ADAMTS-1 expression and myocardial fibrosis in a
      murine model of viral myocarditis].
AB  - OBJECTIVE: To investigate the association between myocardial ADAMTS-1 expression
      and myocardial fibrosis in coxsackievirus B(3) (CVB(3))-induced acute and chronic
      murine myocarditis model. METHODS: Balb/c mice were infected with CVB(3) (single
      injection or monthly injection for 3 months) to establish acute or chronic
      myocarditis model. Normal controls received equal-volume Eagles minimal essential
      medium (EMEM) without CVB(3). Hearts were examined at 7 days or 3 months post
      CVB(3) infection. Heart slides were stained with collagen specific picrosirius
      red staining and the collagen volume fraction (CVF) was calculated with image
      analysis software. The expressions of ADAMTS-1 were determined by RT-PCR and
      immunohistochemistry. RESULTS: Compared with controls, the CVF levels and
      myocardial expressions of ADAMTS-1 were significant increased in two myocarditis
      groups, especially in mice with chronic myocarditis (P < 0.01). The increased
      expression of ADAMTS-1 was located in endochylema as visualized by
      immunohistochemistry. Myocardial ADAMTS-1 mRNA was positively correlated with CVF
      in both myocarditis groups (r(7 days) = 0.65, P < 0.05; r(3 months) = 0.73, P <
      0.01). CONCLUSIONS: ADAMTS-1 increased in proportion with collagen accumulation
      in acute and chronic myocarditis, which might play an important role in the
      development of myocardial fibrosis by modulating the collagen metabolism.

PMID- 18070485
TI  - [The trends in clinical management of hyperlipidemia and goal attainment rate
      from 2000 to 2004 - 2006 in China].
AB  - OBJECTIVE: To compare the clinical management of hyperlipidemia and goal
      attainment rate in year 2000 to year 2004 - 2006 in China. METHOD: Data from 2
      retrospective surveys (2000 and 2004 - 2006) on clinical management of
      hyperlipidemia and goal attainment rate were analyzed. A total of 2136 patients
      were recruited in the 1st survey in year 2000 and 539 patients in the 2nd survey
      in year 2004 - 2006 from 25 and 21 tertiary hospitals of 12 metropolitan cities.
      Eligible patients had hyperlipidemia and received lipid-lowering therapy for more
      than 2 months at the time of survey. Serum lipid levels before and after
      treatment were analyzed and the goal attainment rate post therapy, defined
      according to the Chinese National Recommendations for Prevention and Treatment of
      Dyslipidaemia published in 1997, was calculated. RESULTS: Clinical
      characteristics were comparable in patients from the 1st and 2nd survey: age
      (60.9 and 60.0 years), males (47.2% and 49.3%), type of lipid disorder (mixed
      hyperlipidemia 62.5% and 66.8%), and patients without coronary artery disease
      (CAD 61.2% and 68.6%). The percent of statins use was significantly higher in the
      2nd survey than in the 1st survey (79.2% vs. 70.3%, P < 0.01). The goal
      attainment rate was significantly higher in the 2nd survey than in the 1st survey
      (39.9% vs. 26.6% for all patients, 40.2% vs. 28.8% for hypercholesterolaemia,
      39.7% vs. 25.0% for mixed hyperlipidemia, 45.9% vs. 31.7 for patients without
      CAD, 26.7% vs. 16.6% for patients with CAD, 42.2% vs. 30.1% for patients using
      statins, and 38.5% vs. 28.3% for patients with diet control, all P value < 0.01).
      CONCLUSIONS: Although the goal attainment rate has been significantly increased
      in treated hyperlipidemia patients over recent 5 years in China, it is still far
      from optimal as suggested by the recommendations. Further efforts should be made
      to increase the goal attainment rate in patients receiving lipid-lowering
      therapy.

PMID- 18070486
TI  - [Analysis of etiology of the patients with hypertension from the People's
      Hospital of Xinjiang Uygur Autonomous Region].
AB  - OBJECTIVE: To analyze the etiology of the patients with hypertension from the
      People's Hospital of Xinjiang Uigur Autonomous Region, and to investigate the
      distribution of hypertension in gender and different ages. METHODS: From
      September 1997 to December 2005, the data of 4642 patients with hypertension was
      retrospective studied. RESULTS: (1) Of all the patients, 85.24% were essential
      hypertension (EH) and 14.76% were secondary hypertension (SH). Higher prevalence
      of sleep apnea syndrome (42.92%) and anxiety (15.04%) was found in secondary
      hypertension. The highest prevalence of primary aldosteronism (12.12%) was found
      in endocrine hypertension. (2) The male patients with hypertension were more than
      the female ones, and the incidence of EH, sleep apnea syndrome (SAS) and primary
      aldosteronism was higher in male patients than female ones, and the following was
      less than female: anxiety, pheochromocytoma and renovascular hypertension. (3)
      Among the patients with SH, 21.9% were found in youth, and 9.85% in aged.
      CONCLUSION: For the young, SH should be excluded, especially SAS and anxiety
      should be screened and differentiated. The highest prevalence of endocrine
      hypertension is primary aldosteronism in young and middle-aged male. The
      prevalence of pheochromocytoma in female is higher than that of male.

PMID- 18070489
TI  - [Ischemic cardiomyopathy due to a coronary-pulmonary fistula treated with coil
      embolization].

PMID- 18070490
TI  - [A case report of hypertrophic cardiomyopathy with noncompaction of myocardium].

PMID- 18070491
TI  - [Acute pituitary decompensation occurred in a patient with hypopituitarism after
      percutaneous coronary intervention].

PMID- 18070493
TI  - [Effects of 50 Hz magnetic fields exposure on secretion of primary human villous
      trophoblasts].
AB  - OBJECTIVE: To explore the possible effects of 50 Hz magnetic fields (MF) exposure
      on HCG and progesterone secretion of human villous trophoblasts in vitro.
      METHODS: The trophoblasts were isolated from human villus by trypsin digestion
      and incubated in DMEM medium. Then the trophoblasts were exposed to 0.2 mT, 0.4
      mT 50 Hz MF for 6 h, 12 h, 24 h, 48 h and 72 h, respectively. Each exposure group
      was matched to one control group which was from the same villus and cultured with
      the same condition except the 50 Hz MF exposure. The concentration of human
      chorionic gonadotropin (HCG) and progesterone in the culture medium was detected
      by electrochemiluminescence immunoassay. Statistical significance of differences
      between means was determined by one way-ANOVA with P < 0.05 considered
      significant. RESULTS: Exposure of trophoblasts to 50 Hz MF at 0.2 mT intensity
      within 72 h did not affect the secretion level of HCG and progesterone (compared
      with blank control, P > 0.05). There was also no significant change of the
      secretion level of HCG and progesterone when trophoblasts were exposed to 0.4 mT
      50 Hz MF within 48 h (compared with blank control, P > 0.05). However, 50 Hz MF
      inhibited the HCG and progesterone secretion significantly with exposure for 72 h
      (compared with blank control, P < 0.05). CONCLUSION: The exposure to 50 Hz MF for
      long period could inhibit trophoblasts excreting the HCG and progesterone, and
      the threshold intensity may be between 0.2 mT and 0.4 mT.

PMID- 18070494
TI  - [Apoptosis-related gene expression of human villous trophoblasts exposed to 50 Hz
      magnetic field].
AB  - OBJECTIVE: To study apoptosis-related gene expression of human villous
      trophoblasts exposed to 50 Hz magnetic field and to investigate the possible
      mechanism of human reproductive health effects caused by 50 Hz magnetic field.
      METHODS: Cultured human villous trophoblasts were exposed to 50 Hz magnetic field
      at 0.4 mT for 6, 48, 72 hours. Gene expressions of Bcl-2, Bax, Caspase-3, p53 and
      Fas were analyzed using real-time reverse transcription polymerase chain reaction
      (RT-PCR) assay. RESULTS: Within 72 hours, the average fold change for each gene
      was near 1.00, and there was no significant difference on expression pattern in
      each gene between exposure and control groups (P > 0.05). CONCLUSION: 0.4 mT 50
      Hz magnetic field does not affect the apoptosis-related gene expression of human
      villous trophoblasts in vitro.

PMID- 18070495
TI  - [Hydrargyrism caused by sublimed sulfur and ammoniated mercury lotion in one
      patient].

PMID- 18070496
TI  - [Different therapeutic efficacy of pralidoxime chloride PAM-Cl on AChE against
      acute toxicity of methamidophos, dichlorvos and omethoate].
AB  - OBJECTIVE: To observe the treatments on the patients with acute methamidophos
      dichlorvos (DDV) and omethoate poisoning and provide the reliable basis for the
      rational treatments on these three organophosphorus pesticides poisoning.
      METHODS: 101 patients with AOPP in 7 hospitals were divided into three groups:
      Group A, 59 patients with acute methamidophos poisoning, Group B, 32 patients
      with acute DDV/dipterex (DEP) poisoning, Group C, 10 patients with acute
      omethoate/dimethoate poisoning. The levels of erythrocyte AChE and the
      therapeutic efficacies of pralidoxime chloride (PAM-Cl) were compared among the
      three groups. RESULTS: The AChE activities of all the three groups were inhibited
      on level of (9.12 +/- 7.99) U/g Hb (group A), 7.32 +/- 4.62 U/g Hb (group B) and
      (12.01 +/- 9.53) U/g Hb (group C), among which no significant difference was
      found (P > 0.05). All the patients recovered from acute cholinergic excitation or
      crisis after the treatment of PAM-Cl. The erythrocyte AChE activities were
      obviously reactivated in group A three hours later after admission to hospital,
      each on level of (11.37 +/- 8.67) U/g Hb, (12.51 +/- 6.98) U/g Hb, (15.90 +/-
      7.31) U/g Hb, (18.33 +/- 4.78) U/g Hb and (18.91 +/- 7.00) U/g Hb at the 12th,
      24th, 48th, 72nd hour and discharge (P < 0.05), and the upgrade tendency was
      continuous. AChE activities in group B were also reactivated after treatment,
      each on level of (8.91 +/- 5.89) U/g Hb, (1.31 +/- 6.61) U/g Hb, (13.00 +/- 7.55)
      U/g Hb, (14.22 +/- 7.80) U/g Hb, (12.78 +/- 7.07) U/g Hb and (16.87 +/- 7.06) U/g
      Hb at the 3rd, 12th, 24th, 48th, 72nd hour and discharge, but the upgrade
      tendency turned slowly after 12 hours, the inhibited AChE activities were not
      reactivated in group C from the beginning to the end. CONCLUSION: After the
      treatment of PAM-Cl, the AChE activities of the patients with acute methamidophos
      poisoning could be continuously reactivated, the AChE activities of the patients
      with acute DDV/DEP poisoning could also be reactivated in 12 hours, and then keep
      stable, but the AChE activities of the patients with acute omethoate/dimethoate
      poisoning could not be reactivated. However, PAM-Cl has therapeutic efficacy
      against acute toxicity of all the three organophosphorus pesticides. Oximes
      should be vigorously used in the treatment of AOPP, including acute
      omethoate/dimethoate poisoning.

PMID- 18070497
TI  - [T-cell receptor V alpha gene repertoire and clonal expansion in benzene-exposed
      workers].
AB  - OBJECTIVE: To observe the distribution of TCR V alpha gene repertoire and clonal
      expansion in peripheral blood mononuclear cells from 9 donors and 16 workers
      exposed to benzene. METHODS: Complementarity determining region 3 (CDR3) of TCR V
      alpha subfamily genes were amplified using RT-PCR. The PCR products were further
      analyzed by genescan to evaluate clonality of T cells. RESULTS: Almost all of 29
      V alpha subfamily could be detected in 9 donors. 1 approximately 11 V alpha
      subfamilies were identified in all but one of the workers studied. The most
      frequently expressed V alpha subfamily were V alpha 3, V alpha 12 and V alpha 19
      (68.8%), V alpha 14 (56.3%), with a lower expression rate found in V alpha 5, V
      alpha 15, V alpha 16, V alpha 22, V alpha 23 and V alpha 24 (6.3%). Clonal
      expansion T cells in one or more V alpha subfamily were found in 12 out of all
      workers studied, including oligoclonal, oligoclonal trend and biclonal patterns.
      The frequency of clonal expansion T cells in V alpha 12, V alpha 14 and V alpha
      19 subfamilies were higher than others. CONCLUSION: Skewed distribution and
      clonal expansion of TCR V alpha subfamily T cells could be found in workers
      exposed to benzene. V alpha 12, V alpha 14 and V alpha 19 subfamilies may be
      highly sensitive to benzene exposed. This is the first report of clonal expansion
      TCR V alpha T cells in the benzene-exposed group. The bias pattern of TCR V alpha
      T cells may be due to the immune cytotoxicity from benzene. However, whether the
      oligoclonality in some V alpha subfamilies reflect the phenomenon of clone
      absence or may be a response clone to benzene-related impairment during exposed
      to benzene, remains an open question.

PMID- 18070498
TI  - [Construction of anti-lung tumor gene differentially expressed bank of wild
      mouse].
AB  - OBJECTIVE: To construct the anti-lung tumor gene differentially expressed bank of
      wild mouse and to explore the mechanisms of the TW wild mouse suppressing the
      occurring of lung tumor. METHODS: Using suppression subtractive hybridization
      (SSH) technique, the differentially expressed genes between TAF1 mouse and A/wy
      mouse were selected out and the subtracted cDNA bank was constructed. 166 clones
      were performed DNA sequencing and then were assayed by blast programme. RESULTS:
      Among the blast results of 166 differentially expressed clones, 87 known genes
      (mRNA or cDNA) were in homology with 134 clones and were divided into 7
      classifications according to the biological role.14 DNA fragments were in
      homology with 32 clones, in which 20 clones were in homology with 9 mouse DNA
      sequences, 2 clones were in homology with one bacterial gene sequences and 3
      clones were clone vector. CONCLUSION: With SSH technique, the anti-lung tumor
      gene differentially expressed bank of wild mouse are successfully constructed.

PMID- 18070500
TI  - [Investigation of silicosis and mortality of farmers working in a gold mine].

PMID- 18070499
TI  - [Electrocardiogram change of workers after disengaging occupational noise
      exposure].
AB  - OBJECTIVE: To examine electrocardiogram (ECG) change of workers after leaving
      occupational noise exposure. METHODS: In the first phase of the Guangzhou Biobank
      Cohort Study, 10413 Guangzhou residents aged 50 years or more received a face-to
      face interview including noise exposure history, a full medical check-up and
      laboratory tests in 2003 - 4. ECG examination was carried out using 12-lead MAC
      CS ECG machine made in HP Ltd, Shanghai, China. ECG of every subject was
      independently diagnosed by two doctors who had obtained ECG diagnosis
      qualification. RESULTS: (1) Among 10413 subjects, 70% were female, and more than
      half were aged 60-69 years. The mean age and education level in males were higher
      than those in females. (2) 2119 subjects (21.0%) were previously exposed to noise
      and were retired now. (3) The prevalence of ECG abnormality was respectively
      82.4% and 79.1% in females and males. Rate of ECG abnormality increased with age
      in both females and males (P = 0.000), and was lower in females with higher
      education level (P = 0.000). There was not significant difference in ECG
      abnormality between workers previously exposed or unexposed to noise in both
      females and males (P > 0.05). 4 Comparing workers previously exposed to those
      unexposed to noise in both females and males, after adjusting for age,
      educational level and smoking status, the rates of arrhythmia, axes deviation,
      atria and ventricle hypertrophy, ST-T change and coronary artery syndrome were
      not significantly different (P > 0.05). CONCLUSION: Our study showed that the
      prevalence of ECG abnormality was not significantly increased in workers
      previously exposed to noise and had left exposure now compared to those never
      exposed to noise. Because our study was cross section and occupational history
      was obtained from a questionnaire but was not confirmed by the companies, further
      study is needed.

PMID- 18070501
TI  - [Effect of ammonium perchlorate on expressions of TGF-beta1 and a-mRNA in lung
      tissue of rabbits].

PMID- 18070502
TI  - [PEEP in massive whole lung lavage].

PMID- 18070503
TI  - [Change of activity of serum paraoxonase in patients with acute organophosphorus
      poisoning].

PMID- 18070504
TI  - [Related factors of death in patients with gas burst induced burn].

PMID- 18070505
TI  - [Effect of methylprednisolone pulse therapy combined with blood purification on
      wasp sting induced hemolysis].

PMID- 18070506
TI  - [Athetosis induced by acute benzene and deltamethrin poisoning in one patient].

PMID- 18070507
TI  - [7-aminocephalosporanic acid induced bronchial asthma in two patients].

PMID- 18070509
TI  - [Establishment and application of standards for diagnosis of occupational
      diseases].

PMID- 18070508
TI  - [Intrathoracic drainage in treatment of 43 coal worker's pneumoconiosis patients
      with pleural effusion and pneumothorax].

PMID- 18070510
TI  - [On research of hand-arm vibration disease and suggestions].

PMID- 18070511
TI  - [Current status of occupational hazard and control in small and medium
      enterprises].

PMID- 18070512
TI  - [Current status of overseas certification system of registered occupational
      health doctors].

PMID- 18070513
TI  - [Promotion of rational return of subject consciousness of enterprise social
      responsibility].

PMID- 18070514
TI  - [Preliminary design for establishment of registered occupational health doctors
      certification system in China].

PMID- 18070515
TI  - [Current status and prospect for application of single nucleotide polymorphism
      research in occupational health].

PMID- 18070517
TI  - [Pay more attention to early diagnosis and intervention for patients with primary
      glaucoma].
AB  - Primary glaucoma is an irreversible serious blindness disease. Early diagnosis
      and intervention is the key measure for prevention of visual function from damage
      in patients with primary glaucoma. The progress of the basic and clinical
      research on primary glaucoma in recent years, such as classification of primary
      angle closure glaucoma (PACG), the risk factors of PACG, the management of PACG,
      the change of the optic nerve head in primary open angle glaucoma (POAG), and the
      concept of target pressure in management of primary glaucoma, has greatly
      promoted the early diagnosis and intervention for the patients with primary
      glaucoma. By taking the measures including strengthening the continuing medical
      education of early diagnosis and intervention for primary glaucoma to
      ophthalmologists and ophthalmic residents, popularizing the knowledge of glaucoma
      to public, and screening the early primary glaucoma patients and suspects via the
      way of the public health survey, more patients with primary glaucoma will be
      early diagnosed and managed. Thus, the rate of blindness in glaucoma patients
      will decrease.

PMID- 18070518
TI  - [To reinforce the collection and usage of the genetic resource of glaucoma in
      China].
AB  - Positive family history is one of the risk factors of glaucoma. It indicates that
      gene defect may play an important role in the development of glaucoma. The
      advancement of genetic research provides more strategies to understand the
      genetic mechanism of glaucoma. The precondition of understanding and studying the
      genetic factors is the possession of enough genetic resource related to diseases.
      Based on the usage of glaucomatous genetic resources, several genes and loci
      related to primary glaucoma were determined abroad. Although we hold the richest
      human genetic resources of diseases in China, there exist some problems in the
      collection, storage and usage of the genetic resources of diseases, including the
      lack of the strict guideline in practice, the lack of the active participant from
      the clinician, not closely work together of the researchers and clinician, in
      sufficiently use of the genetic resources, loss of the genetic resources. We
      should envisage these problems. At present, it is urgent to rationally and use
      the genetic resource in China.

PMID- 18070519
TI  - [The prevalence of primary angle-closure glaucoma and its causes in rural area of
      Shuangyang district in Changchun, Jilin province].
AB  - OBJECTIVE: To investigate the prevalence of primary angle-closure glaucoma (PACG)
      and its causes in a rural area in Changchun, China. METHODS: From the rural area
      of Qijiaxiang, Shuangyang district of Changchun, 1139 individuals aged 40 years
      and above were randomly selected for the study from September 2004 to February
      2005 using Zhao Jialiang's standard. All subjects in this study underwent a
      preliminary screening examination including visual acuity, the peripheral depth
      of anterior chamber, slit lamp, tonometry and fundus. The suspects of PACG were
      asked to repeat the following examinations: tonometry, gonioscopy, fundus, and
      visual field assessment. RESULTS: 1139 of 1528 subjects were invited to
      participate in the study (response rate 74.5%). In those age 40 years and above,
      the prevalence of PACG was 1.5% in men, 3.5% in women, and 2.5% in general
      population, respectively. The prevalence was increased with age. The anterior
      chamber was significantly (P<0.01) narrower in the female group than in the male
      group when the peripheral depth of anterior chamber was compared. The prevalence
      of PACG was significantly (P<0.02) higher in subjects with positive family
      history than with negative family history. CONCLUSIONS: In the rural area in
      Shuangyang district of Changchun, the prevalence of PACG is higher than other
      regions surveyed in China. Sex, age, family history and the peripheral depth of
      anterior chamber are significant risk factors in PACG.

PMID- 18070520
TI  - [Analysis of the CYP1B1 gene mutation in primary congenital glaucoma patients of
      Hubei Han nationality].
AB  - OBJECTIVE: To identify novel CYP1B1 gene mutation in primary congenital glaucoma
      (PCG) patients of Hubei Han nationality and establish the possibility of gene
      diagnosis of PCG. METHODS: Forty-seven patients with PCG and 100 normal subjects
      were studied. Genomic DNA was extracted from the peripheral leukocytes of all
      subjects. Mutation in exon2 and exon3 of CYP1B1 gene was detected in patients and
      control subjects by polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP), denaturing high performance liquid chromatograph
      (DHPLC), and direct sequencing DNA techniques. RESULTS: Compared to normal
      subjects, a novel mutation was first time identified by direct sequencing
      demonstrating a homozygous C-to-T transition at codon 385 (CTT to TTT) which
      produced L385F mutation of CYP1B1 gene in 7 of the 47 patients with PCG.
      CONCLUSIONS: The novel mutation in exon 3 of CYP1B1 found in PCG patients of
      Hubei Han nationality was probably pathological mutant gene by nature. It is
      important that further study be conducted to seek for the specific mutations of
      CYP1B1 gene and underlying pathological mechanism of PCG patients of Han
      nationality.

PMID- 18070521
TI  - [Comparison of peripapillary atrophy in eyes with unilateral visual field defect
      in patients with primary open-angle glaucoma and normal tension glaucoma].
AB  - OBJECTIVE: To evaluate the difference of the peripapillary atrophy between two
      eyes of unilateral visual field defect in each of patient with primary open-angle
      glaucoma (POAG) and normal tension glaucoma (NTG). METHODS: This study included
      40 eyes with unilateral visual field defect in patients with POAG (20 cases) and
      NTG (20 cases). Color stereo optic disc photographs were morphometrically
      evaluated by a video camera and a computer system. The refractive range
      (spherical equivalent) of all these subjects was between -3.00D and +3.00D.
      RESULTS: The cup areas (CA) and cup/disc areas (CA/DA) in eyes with visual field
      defect were significantly larger than in eyes with normal visual field (CA:
      t=5.332, P<0.01; CA/DA: t=5.126, P<0.01). The alpha zone areas (alphaA) of PPA
      were significantly enlarged in visual field defect eyes compared with visual
      field normal eyes (t=3.02, P=0.0045), while there is no significant difference in
      beta-zone area (betaA) between two eyes. (S=13.5, P=0.426). The frequency of the
      PPA (alpha-zone and beta-zone) occurrence were also similar in both eyes.
      (alphaA: chi(2)=0.00, P=1.000; betaA: chi(2)=1.2857, P=0.2568). CONCLUSION: The
      results suggest that either beta-zone area or the presence of PPA is not closely
      correlated to the visual field defect in POAG and NTG patients with exclusion of
      moderate or high myopia.

PMID- 18070522
TI  - [Long-term follow-up and management of choroidal osteoma].
AB  - OBJECTIVE: To report the clinical characteristics, long-term follow-up and
      management of choroidal osteoma. METHODS: Eighteen eyes of 12 cases (5 male and 7
      female) of choroidal osteoma were studied. Best corrected vision, intraocular
      pressure, perimetry, anterior segment and eye fundus were examined routinely.
      Special tests included phytochrome of eye fundus, fluorescein angiography and/or
      indocyanine green angiography; B-ultrasonogram, CT, perimetry and
      electrophysiology. (1) Eight eyes of 6 cases treated with vitamins and anti
      inflammatory drug and followed-up periodically for 1-26 years (median 2.5 years).
      (2) Four eyes of 2 cases were treated with Krypton laser photocoagulation, 2 of
      them were superimposed with transpupillary thermotherapy (TTT). (3) TTT was given
      primarily for 6 eyes of 4 cases with infrared dione laser; the spot size was 3
      mm, 1-5 spots were conducted conjunctly to cover the tumor surface. Power was 800
      1200 mw at 60-90 seconds. The procedure was completed in 1-3 recessions with an
      interval of 4-6 weeks. RESULTS: (1) In the medical treatment group, gradual
      growth of the tumor with pseudopodium along the margin was disclosed. One eye
      showed spontaneously regression during the long-term follow-up. (2) Laser
      photocoagulation was effective for 2 eyes, but residual flat serous detachment
      around the optic disc persisted in another 2 eyes and subsided with TTT. (3)
      Choroidal osteoma complicated with CNV treated primarily with TTT, prominent
      improvement was demonstrated. CONCLUSIONS: Choroidal osteoma grows gradually in
      the natural course and shows pseudopodial margin. Laser photocoagulation was
      effective for certain cases. TTT is a method of choice either used primarily or
      supplementary after laser photocoagulation, it is recommended for cases
      complicated with CNV.

PMID- 18070523
TI  - [Leber hereditary optic neuropathy and optic neuritis: similarities and
      differences of clinical characteristics].
AB  - OBJECTIVE: To compare the clinical characteristics of Leber hereditary optic
      neuropathy (LHON) with optic neuritis (ON). METHODS: The information of clinical
      manifestation and laboratory tests in 55 patients with LHON and 48 patients with
      ON were reviewed and analyzed. RESULTS: Compared with ON, LHON was more commonly
      found in male patients (46/55 vs 21/48) and onset at younger age (median 16 years
      vs 30 years). There were more LHON than ON patients with the decrease of visual
      acuity lasted more than two weeks (42/49 vs 10/48), severe damage in visual
      acuity whereas little pain sensation in eye associated with eye movement (3/55 vs
      26/48), dominant single-phase course (53/55 vs 30/48), central scotoma (26/39 vs
      12/35), and family history of maternal relatives (25/50 vs 2/48). The visual
      evoked potential, cerebral spinal fluid and brain magnetic resonance scanning
      revealed the involvement of inflammatory demyelination in the patients with LHON.
      Most patients with LHON could be confirmed by the mtDNA mutation examination.
      CONCLUSIONS: Leber hereditary optic neuropathy has distinct clinical
      characteristics but overlap with optic neuritis in many aspects. mtDNA mutation
      examination can further confirm LHON in most of patients although a negative
      result may be seen in a small portion of patients showing typical manifestation
      of LHON.

PMID- 18070524
TI  - [Comparative studies of wavefront aberration and contrast sensitivity after
      phacoemulsification and intraocular lens implantation].
AB  - OBJECTIVE: To study the difference of the contrast sensitivity and wavefront
      aberration of two eyes who undergone phacoemulsification and intraocular
      transplantation respectively. METHODS: Sixty-three patients with cataract were
      included in the study. With the consent of the patients, one eye was implanted
      SA60AT intraocular lens and another eye was implanted Tennis Z9001 intraocular
      lens after phacoemulsification. One and three months post-surgery, the best
      corrected visual acuity was recorded by computer and comprehensive optometry.
      Contrast sensitivity was analyzed by CSV-1000. The corneal aberration was
      measured by Option Keratron Scout. The whole ocular aberration was evaluated by
      Allegretto Waver Analyzer at pupillary diameter 4 mm and 6 mm. RESULTS: The best
      corrected visual acuity and the corneal spherical aberration, corneal coma
      aberration and RMS had no significant difference between the two groups. After
      one and three months, the contrast sensitivity of 3, 6, 12, 18c/d had statistic
      significance between the eye with and without glare through univariate split-plot
      analysis. The Z9001 contrast sensitivity value was much higher than the SA60AT
      groups. The results of Zernike polynomials C12, RMS4 and RMSh had statistic
      significance between the two groups through T-test. The Z9001 group value was
      much lower than the SA60AT groups. CONCLUSIONS: The Z9001 intraocular lens
      transplantation can reduce total ocular aberration, special the spherical
      aberration and improve visual acuity.

PMID- 18070525
TI  - [A survey of blindness and low vision in Motuo county of Tibet].
AB  - OBJECTIVE: To investigate the status of blindness and low vision in Motuo county
      of Tibet. METHODS: Random cluster sampling based on the village was adopted in
      this survey. Six villages were chosen as the survey venue. The sampling
      percentage was 2.05% in the whole population in the county. The criteria of
      blindness and low vision from World Health Organization were used in the survey.
      RESULTS: 821 individuals were registered. The rate of final participants was
      89.52%. The prevalence of bilateral blindness and low vision was found to be
      2.59% and 4.35% respectively. Subjects over 40 years old had a significantly
      higher prevalence of blindness and low vision. The causes leading to blindness
      and low vision were cataract (42.11%), corneal opacity (21.05%) and glaucoma
      (15.79%). CONCLUSION: The leading cause of blindness and low vision is cataract
      in Motuo county, therefore the surgical application in cases with cataract is the
      main measure in the treatment of blindness in the county.

PMID- 18070526
TI  - [A novel retrograde intubation procedure for treatment of nasolacrimal duct
      obstruction].
AB  - OBJECTIVE: To investigate the effect of a novel intubation procedure for the
      treatment of nasolacrimal duct obstruction. METHODS: Nasolacrimal duct
      obstruction patients with chronic dacryocystitis were selected for undergoing the
      procedure of intubation in outpatient clinic. This procedure was performed under
      local anesthesia. Retrograde intubation was inserted into the nasolacrimal duct
      and guided with probing. The location of drainage tube, cleanliness, epiphora,
      secretion from lacrimal sac and other signs were observed 2-4 weeks after
      intubation. Patients were grouped according to postoperative follow-up time.
      Group A consisted 521 cases (613 eyes) who underwent operations from May 1997 to
      December 2001 in Shenzhen Ophthalmic Hospital and observed for 3-5 years to
      evaluate long-term results. Group B consisted 381 cases (411 eyes) who underwent
      operations from October 2003 to October 2005 in Shenzhen Ophthalmic Hospital and
      5 cases (6 eyes) who underwent operations at the same time period in Beijing
      Shunyi District Hospital (a total of 386 cases, 417 eyes) and observed for 0.5
      1.5 years as the recent treatment group. The cure rates of these two groups were
      compared using the chi-square test. RESULTS: The lacrimal system was able to be
      irrigated one week after the operation. Epiphora symptoms were eliminated 2-3
      weeks postoperatively. Lacrimal sac secretions disappeared within 1-3 weeks in
      most cases, few patients still had mucous secretions after 3 weeks and needed the
      second intubation operation. The cure rate of second intubation was 92.3%
      (23/26). The cure rates of Group A and Group B were 84.5% and 88.2%,
      respectively. There was no significant difference in cure rate between these two
      groups. Surgery and anesthesia could lead to a short period of diplopia and
      discomfort without any other complications. CONCLUSIONS: The novel lacrimal
      retrograde tube and the operation procedure are safe, simple and without obvious
      trauma. The prognosis of the intubation operation is good and this method could
      be used as a treatment for nasolacrimal duct obstruction and chronic
      dacryocystitis.

PMID- 18070527
TI  - [The effect of lentivirus-mediated suicide gene therapy on lens epithelial
      cells].
AB  - OBJECTIVE: To investigate the cytotoxicity of lentivirus-mediated herpes simplex
      virus thymidine kinase/ganciclovir (HSV-TK/GCV) suicide gene therapy on human
      lens epithelial cell line and analyze the mechanism of cell death. METHODS: a
      lentiviral containing the Lenti-HSVtk-EGFP as therapeutic vector and Lenti-EGFP
      as the control were used in the study. Transfection efficiency in vitro was
      assessed by fluorescence-activated cell sorting. Expression of HSV-tk in lens
      epithelial cells (LECs) mediated by lentivirus was examined by fluorescence
      microscope, genomic PCR and reverse transcription PCR. The cytotoxicity of HSV
      TK/GCV suicide-gene system was assessed using DNA ladder and electron microscope.
      The time dependent transfection efficiency and bystander effect induced by the
      HSV-TK/GCV in LECs were evaluated. RESULT: the transduction efficiency was higher
      than 95%. When concentration of GCV was 15-25 microg/ml, apoptosis or necrosis
      was induced by Lenti-HSVtk-EGFP in HLE. The cytotoxicity was enhanced with
      increased time of transfection and concentration of GCV. Non transfected cells
      were also effectively killed by mixing the cell with GCV transfected cells
      (Bystander effect). CONCLUSION: GCV can effectively kill the LECs with the
      expressing of HSV-tk. Bicistronic lentiviral vectors can efficiently integrate
      multiple genes into LECs, therefore, it is a reliable vector for gene therapy;
      lentivirus mediated HSV-tk/GCV suicide gene therapy may provide an effective
      approach for the treatment of posterior capsule opacification.

PMID- 18070528
TI  - [The roles of gelatinases in pathological changes of fungal keratitis in
      experimental rabbits].
AB  - OBJECTIVE: To study the roles of gelatinases, including matrix metalloproteinase
      (MMP)-2 and MMP-9, in pathological changes of fungal keratitis in rabbits.
      METHODS: Eighty New Zealand albino rabbits were randomly and equally divided into
      4 groups, 3 of them were test groups, with Fusarium solani, Aspergillus
      fumigatus, and Candida albicans inoculated onto the right corneas, respectively.
      In the other group, sterile saline was injected onto the right corneas and was
      used as the control group. The source and activity of gelatinases were examined
      by immunohistochemistry and gelatin zymography, respectively. Hematoxylin-eosin
      stains was applied for observing infiltration of inflammatory cells and
      degradation of corneal extracellular matrixes (ECMs). Periodic acid-Schiff stain
      was used for studying hyphal growth patterns and the invasive depth in the
      cornea. RESULTS: MMP-2 was mainly produced by the keratocytes. Active MMP-2 was
      detected from day 5 after inoculation and increased greatly on day 8. MMP-9 was
      mostly produced by neutrophils, and active MMP-9 was detected from day 1 and
      increased to day 3, then decreased gradually. In A. fumigatus and C. albicans
      keratitis, the corneal ECMs were degraded obviously, the hyphae grew vertically,
      and the neutrophils were much more than those in F. solani keratitis whose hyphae
      grew horizontally and ECMs were degraded slightly. On day 8, the hyphae and
      neutrophils in F. solani and C. albicans keratitis decreased greatly compared
      with day 3, but did not change significantly in A. fumigatus keratitis.
      CONCLUSIONS: There is significant difference in gelatinase activities in the
      rabbits' corneas infected by F. solani, A. fumigatus, and C. albicans.
      Gelatinases play important roles in the degradation of corneal ECMs. Hyphal
      growth pattern and invasive depth are depended on the difference of degradations
      of ECMs and show difference in various fungal keratitis.

PMID- 18070529
TI  - [The genes associated with termination of the critical period of neuroplasticity
      in visual cortex].
AB  - OBJECTIVE: To screening genes associated with termination of the critical period
      of neuroplasticity in visual cortex and investigate the molecular mechanism.
      METHODS: To construct a cDNA library using visual cortex of dark rearing rats and
      normal light rearing 1 week after dark rearing 60 days rats with suppression
      subtractive hybridization technique. PCR, reverse Northern hybridization,
      sequencing and homology search were used to analysis the differential expression
      genes fragments. RESULTS: The cDNA library of termination the critical period was
      set up successfully. After screening, sequencing and homology search 14 sequences
      were obtained. Among of the genes 13 were known genes and one was novel gene
      fragment. They were up-regulated genes in visual cortex when the critical period
      termination. CONCLUSIONS: Through construction the cDNA library, we screened a
      crop of candidate genes related to termination the critical period. The results
      provided important foundation to further illuminate the molecular mechanism of
      termination the critical period of neuroplasticity in visual cortex.

PMID- 18070530
TI  - [Productivity and cited pattern of the authors in Chinese Journal of
      Ophthalmology 2001-2006].
AB  - OBJECTIVE: To evaluate the researcher's productivity by analyzing the citation
      statue of articles published in Chinese Journal of Ophthalmology (CJO). METHOD:
      Using the database of Chinese Medical citation Index (CMCI), the citations from
      the CJO were collected and analyzed with the bibliometric methods. RESULT: 1513
      papers were published in CJO by 990 authors from 2001-2006 (6 years). 2611
      citations by all different journals were found from 705 CJO papers by 479
      authors. 748 authors (75.6% of total first authors) published only one paper,
      while 50 core authors published over 4 papers during 6 years. Beijing was ranked
      the first with 412 papers and 666 citations, Guangdong Province the second with
      235 papers and 632 citations according to the distribution. 851 papers (55.6%)
      and 1611 (61.7%) citations were from 17 well-respected institutions. The top of
      rank was Zhongshan Ophthalmic center of SUN Yat-sen University with 198 papers
      and 526 citations, followed by Beijing Tongren Ophthalmic Center of Capital
      University of Medical Sciences with 140 papers and 237 citations. CONCLUSIONS:
      The results indicate that the published papers from CJO in recent 6 years are
      extensively cited, suggesting that the core authors are active and publish most
      important papers. Beijing, Guangdong and shanghai are most productive in
      publication of article in CJO even though the authors are widely distributed in
      the nation.

PMID- 18070531
TI  - [Statistics of internationally-issued English articles on ophthalmology by
      mainland Chinese authors during the past 6 years].
AB  - OBJECTIVE: To understand and to analyze the overall situation of ophthalmic
      research articles issued in English internationally by mainland Chinese authors
      during the past 6 years. METHODS: Using relevant retrieval words to search the
      articles from the PubMed, the largest database in biology and medical science in
      the world, and to conduct a statistical analysis. RESULTS: Three hundred and
      ninety two English ophthalmological articles by mainland Chinese researchers as
      the first author or first organization were published in 134 periodicals. Most of
      these organizations were medical universities (as well as their affiliated
      hospitals) and China Academy of Science. There were 23 journals which published
      more than 4 articles and there were 25 organizations issued more than 4 articles.
      CONCLUSIONS: During the past 6 years, there was a significant increase in the
      number of articles issued internationally by mainland Chinese authors, indicating
      an enormous progress in the field of ophthalmic research in mainland of China.

PMID- 18070540
TI  - [Role of immune system in glaucomatous optic nerve degeneration].
AB  - Glaucoma is a chronic neurodegenerative disease characterized by progressive loss
      of retinal ganglion cells and optic nerve axons, and accompanying loss of visual
      field sensitivity. With the development of immunology, compelling evidence
      obtained suggests the involvement of immune system regulation in glaucomatous
      optic nerve degeneration. Despite the neuroprotective features of immune system,
      an autoimmune component resulting from a failure to properly control aberrant and
      stress-induced immune response likely lead to the progression of
      neurodegeneration in glaucoma. A better understanding of the diverse roles of the
      immune system in all forms of glaucomatous optic nerve degeneration will
      facilitate the development of effective neuroprotective strategies in glaucoma.
      The effect of immune system on glaucomatous neuropathy is reviewed in this
      article.

PMID- 18070541
TI  - [The past, present and future in pulmonary hypertension].

PMID- 18070542
TI  - [The current situation and strategies in management of pulmonary arterial
      hypertension in China].

PMID- 18070543
TI  - [Vasoconstriction and remodeling in pulmonary arterial hypertension].

PMID- 18070544
TI  - [On the learning and application of new knowledge in pulmonary arterial
      hypertension].

PMID- 18070545
TI  - [The concept and clinical classification of pulmonary hypertension].

PMID- 18070546
TI  - [Advances in drug therapy for pulmonary arterial hypertension].

PMID- 18070547
TI  - [Apoptosis versus proliferation activities of pulmonary artery smooth muscle
      cells in pulmonary arterial hypertension associated with chronic obstructive
      pulmonary disease].
AB  - OBJECTIVE: To investigate the apoptosis versus proliferation activities of
      pulmonary artery smooth muscle cells (PASMC) in pulmonary hypertension (PH)
      associated with chronic obstructive pulmonary disease (COPD) and pulmonary
      vascular structural remodeling. METHODS: Forty-five patients were divided into
      three groups: patients without COPD and PH (non-COPD group, n = 15), COPD
      patients without PH (COPD with non-PH group, n = 15) and patients with PH
      associated with COPD (COPD with PH group, n = 15). Lung tissue samples were
      obtained from surgically resected specimens. The remodeling of pulmonary arteries
      were observed under microscope, and the changes of morphology-the ratio of the
      thickness of the wall to the external diameter of the pulmonary arterioles (WT%)
      and the ratio of the area of the wall to that of the pulmonary arterioles (WA%)
      were analyzed by computer-based image analysis system. The proliferation of PASMC
      was detected by proliferating cell nuclear antigen (PCNA) with
      immunohistochemical technique, and TUNEL (terminal deoxynu-cleotidyl transferase
      (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling)
      was used for the detection of the apoptosis of PASMC. RESULTS: In the COPD with
      non-PH group, the arterial walls were thicker and the lumens narrower than that
      of the non-COPD group. In the COPD with PH group, the walls were thicker and the
      lumens narrower than that of the COPD with non-PH group. In the COPD with non-PH
      group and the COPD with PH group, the WT% and WA% [(20 +/- 4)% and (35 +/- 5)%;
      (28 +/- 5)% and (50 +/- 6)%, respectively] were higher than those of the non-COPD
      group (16 +/- 3)% and (25 +/- 3)% (P < 0.01), and the WT% and WA% of the COPD
      with PH group were higher than those of the COPD with non-PH group (P < 0.01).
      Both proliferative and apoptotic PASMC were found in the patients of the three
      groups. The proliferation indexes (PI) of the COPD with non-PH group and the COPD
      with PH group [(19 +/- 5)% and (38 +/- 7)%] were significantly higher than that
      of the non-COPD group [(8 +/- 2)%, P < 0.01], while the apoptosis indexes (AI)
      [(4.5 +/- 1.3)% and (3.1 +/- 1.3)%] were lower than that of the non-COPD group
      [(6.9 +/- 1.9)%, P < 0. 01]. The PI of the COPD with non-PH group was lower than
      that of the COPD with PH group; the AI was higher than that of the COPD with PH
      group (P < 0.05). The PaO(2) of the COPD with non-PH group and the COPD with PH
      group was negatively related with the PI (r = -0.519, P = 0.003), but positively
      related to the AI of the PASMC (r = 0.441, P = 0.015). CONCLUSION: The imbalance
      of the increased proliferation and decreased apoptosis of PASMC may contribute to
      the pulmonary vascular structural remodeling and pulmonary arterial hypertension
      in patients of COPD. Hypoxia is one of the main causes of increased proliferation
      and decreased apoptosis of the PASMC.

PMID- 18070548
TI  - [The role of bone morphogenetic protein-2 in the pathogenesis of hypoxic
      pulmonary hypertension].
AB  - OBJECTIVE: To investigate the change of bone morphogenetic protein-2 (BMP-2) in
      the lung tissues of rats with hypoxic pulmonary hypertension (HPH) and the role
      of BMP in the apoptosis of endothelial cells exposed to hypoxia. METHODS: Twenty
      male Wistar rats were randomly divided into two groups, the HPH group and the
      control group, 10 rats in each group. The HPH model was established by placing
      the rats in an isobaric chamber [O(2) = (10 +/- 0.5)%] for three weeks. The
      distribution of BMP-2 in pulmonary tissues was observed by using streptavidin
      peroxidase method (SP), and the morphologic changes of pulmonary arterioles and
      the integrated optical density (IA) of BMP-2 were determined by image analysis.
      The effect of Noggin (a blocking agent of BMP) on the apoptosis of hypoxic
      cultivated human umbilical vein endothelial cells (HUVEC) was assayed by flow
      cytometers. RESULTS: Compared to the control group, pulmonary artery hypertension
      was evident in the hypoxic rats: mPAP was 16.3 +/- 0.5 mm Hg (1 mm Hg = 0.133
      kPa) vs (29.5 +/- 0.9) mm Hg, P < 0.01. In the hypoxic rats, the pulmonary
      arteriolar wall thickened significantly; WT% was (16 +/- 5)% vs (27 +/- 7)%, and
      WA% was (54 +/- 11)% vs (80 +/- 8)%, both P < 0.01. The distribution of BMP-2 was
      mainly in the pulmonary arteriolar walls. The IA of BMP-2 significantly increased
      (6124 +/- 1199 vs 13 463 +/- 5755, P < 0.01), and showed a positive linear
      relationship to WT% and WA% respectively (WT%: r = 0.744 P < 0.01; WA%: r = 0.693
      P < 0.01). Hypoxia induced apoptosis of HUVEC; the apoptosis rate was increased
      from 6% to 14% and 25% after exposure to hypoxia for 24 h and 48 h respectively.
      The HUVEC apoptosis rate induced by hypoxia was reduced by Noggin to 11.91% (24
      h) and 15.01% (48 h). CONCLUSIONS: Chronic hypoxia induced an increased
      expression of BMP-2, and a blocking agent of BMP inhibited the apoptosis of
      endothelial cells induced by hypoxia. It suggests that BMP may play an important
      role in the pathogenesis of hypoxic pulmonary hypertension.

PMID- 18070549
TI  - [The changes of serum enzymes and cardiac troponin I in patients with acute
      pulmonary thromboembolism].
AB  - OBJECTIVES: To investigate the changes of serum enzymes and cardiac troponin I
      (TnI) in patients with acute pulmonary thromboembolism (PTE). The relationships
      between these changes and the pulmonary artery pressure, the right ventricular
      function and the prognosis were evaluated. METHODS: This prospective multi-centre
      trial included 519 patients with confirmed PTE from 24 collaborating hospitals,
      with 54 cases of massive PTE, 195 sub-massive PTE and 270 non-massive PTE.
      Thrombolytic treatment with urokinase or recombinant tissue plasminogen activator
      (rt-PA) was administered for massive and sub-massive PTE patients; anti
      coagulative therapy with unfractionated heparin or low molecular weight heparin
      was used for non-massive PTE. RESULTS: The values of serum ALT, AST, CPK and LDH
      before treatment in massive PTE [(74 +/- 33), (88 +/- 40), (157 +/- 75), (419 +/-
      264) U/L] were significantly higher than those in sub-massive [(52 +/- 21), (43
      +/- 18), (75 +/- 30), (284 +/- 176) U/L] and non-massive cases [(38 +/- 13), (35
      +/- 11), (78 +/- 24), (239 +/- 178) U/L] (P < 0.05). The value of serum ALT at
      day 7 (84 +/- 39 U/L) in the unfractionated heparin sub-group of the non-massive
      PTE was significantly higher than that (67 +/- 26 U/L) in the low molecular
      weight heparin sub-group (P = 0.045). Of the 45 cases with high pulmonary
      pressure > 80 mm Hg (1 mm Hg = 0.133 kPa), 24 (54.4%) cases showed high serum LDH
      (P = 0.032) and 17 (41.5%) high serum ALT (P = 0.049). Of the 169 cases with
      right ventricular dysfunction, 68 (40.2%) cases showed high serum LDH (P = 0.049)
      and 76 (45.5%) high serum ALT (P = 0.037). Of the 48 cases with poor prognosis,
      15 (30.8%) cases showed high serum LDH (P = 0.039) and 26 (54.5%) high serum ALT
      (P = 0.022). Of the 39 cases with TnI > or = 0.07 microg/L, 24 (63.3%) cases were
      complicated with decreased right ventricular function (P < 0.01) and 8 (24.2%)
      with poor prognosis (P = 0.034). CONCLUSIONS: The values of serum ALT, AST, CPK,
      LDH and TnI are increased in acute PTE. Unfractionated heparin results in higher
      levels of ALT than lower molecular weight heparin. The increase of serum ALT, LDH
      and TnI is correlated with pulmonary artery pressure, right ventricular function
      and the prognosis of the PTE. These changes may be useful in the risk
      stratification of PTE patients.

PMID- 18070550
TI  - [Respiration control dysfunction and the relationship to sleep-disordered
      breathing in patients with chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To analyze the polysomnographic (PSG) features of sleep apnea hypopnea
      syndrome (SAHS) in patients with chronic obstructive pulmonary disease (COPD),
      and to define the association between SAHS and respiratory control disorder.
      METHODS: Three hundred patients with stable COPD were screened for SAHS using
      questionnaire, Epworth sleep scale (ESS) and home pulse oximeter testing. Those
      with ESS > or = 10 or oxygen desaturation over 3% more than 5 times per hour
      sleep were under further PSG testing. The PSG features were compared between COPD
      patients with apnea hypopnea index (AHI) > 10 and 118 SAHS patients with normal
      lung function. The two groups were matched for age, body mass index (BMI) and
      AHI. Among them 22 with COPD and AHI > or = 10 were tested for the chemo
      responsiveness to isocapnic hypoxia and hypercapnia. RESULTS: Among the 300
      patients with stable COPD, 79 had AHI over 10, meeting the diagnostic criteria of
      overlap syndrome (OS). Analysis of the polysomnography found that 32 cases (40%)
      with OS had more hypoventilation lasting over 1 min during sleep. Compared to
      patients with SAHS only, OS patients had higher percentage of hypopnea index over
      AHI [(69 +/- 30)% vs (52 +/- 31)%] and a higher percentage of total hypopnea time
      over total time of sleep apnea and hypopnea [(15 +/- 12)% vs (12 +/- 10)%]. OS
      patients also had lower hypoxic [(-0.11 +/- 0.05) vs (-0.35 +/- 0.24) L.min(
      1).%(-1)] and hypercapnic responses [(1.1 +/- 0.8) vs (1.6 +/- 0.8) L.min(-1).mm
      Hg(-1) (1 mm Hg = 0.133 kPa)]. CONCLUSION: Patients with both COPD and SAHS had
      more episodes of hypopnea and hypoventilation during sleep, and had depressed
      chemo-responsiveness to hypoxia during wakefulness.

PMID- 18070551
TI  - [Effects of bone marrow mesenchymal stem cells on bleomycin induced pulmonary
      fibrosis in rats].
AB  - OBJECTIVE: To study the effects of bone marrow mesenchymal stem cells (MSC) on
      pulmonary fibrosis. METHODS: Bone marrow MSC were harvested from 6 week old male
      SD rats. Forty-eight female SD rats were randomly divided into six groups. The
      pulmonary fibrosis models were made by intratracheal instillation of bleomycin (5
      mg/kg in 0.3 ml normal saline). The normal controls received intratracheal
      instillation of NS instead of bleomycin. On the 1st and 7th day after bleomycin
      administration, the rats received MSC infusion or a same amount of phosphate
      buffer solution (PBS) as controls via the tail vein, respectively. The rats were
      sacrificed by the 28 day of experiment, and the pathologic changes and
      hydroxyproline contents of the lung tissues were investigated. The sry gene of Y
      chromosome was detected by polymerase chain reaction (PCR). RESULTS: For rats
      receiving MSC on the 1st and 7th day after bleomycin administration, the lung
      fibrotic scores were 1.0 +/- 0.2 and 1.6 +/- 0.5, respectively, significantly
      decreased as compared with rats receiving no MSC (2.5 +/- 0.5 & 2.3 +/- 0.8,
      respectively). The hydroxyproline contents of lung tissue were (83 +/- 17)
      microg/mg and (96 +/- 20) microg/mg, also significantly decreased as compared
      with rats receiving no MSCs [(123 +/- 32) microg/mg & (127 +/- 34) microg/mg,
      respectively]. Earlier administration of MSCs resulted in more significant
      improvement of lung injury. The sry gene (322 bp) was detected in lungs of female
      rats receiving MSC on the first day of bleomycin induced lung injury.
      CONCLUSIONS: MSC may be involved in the repair of lung injury, especially in the
      early stage. MSCs are effective in preventing bleomycin induced lung injury and
      fibrosis.

PMID- 18070553
TI  - [Mutations in the thymidylate synthase gene is a major mechanism in the para
      aminosalicylic acid resistance of M. tuberculosis].
AB  - OBJECTIVE: The mechanisms of resistance to para-aminosalicylic acid (PAS) are
      undefined. In this study, we explored the mechanisms of M. tuberculosis PAS
      resistance in clinical isolates. METHOD: The whole sequence of thymidylate
      synthase (thyA) gene encoding thyA genes was sequenced in 51 para-aminosalicylic
      acid (PAS)-sensitive and 44 resistant M. tuberculosis clinical isolates. RESULTS:
      Sixteen of 44 resistant M. tuberculosis clinical isolates had mutations in the
      thyA genes, a mutation rate of 36.4% (16/44). No mutations were detected in the
      sensitive clinical isolates. The mutation types included substitutions,
      conversions and deletions. CONCLUSIONS: Mutations in the thyA gene is associated
      with PAS resistance in M. tuberculosis clinical isolates, and mutations in thyA
      gene probably represent a major mechanism of developing resistance to the drug.
      Thymidylate synthase is likely to be the target of PAS action.

PMID- 18070554
TI  - [Application of quantitative polymerase chain reaction in the differentiation of
      sarcoidosis and proliferative tuberculosis].
AB  - OBJECTIVE: To evaluate the role of mycobacterial infection in the pathogenesis of
      sarcoidosis by examination of mycobacterial DNA in tissue samples of sarcoidosis
      and tuberculosis, and to examine the value of quantitative real-time polymerase
      chain reaction (PCR) in the differentiation of the two diseases. METHODS:
      Mycobacterium tuberculosis DNA was measured by quantitative real-time PCR from
      formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes
      and lung tissues from 31 patients with sarcoidosis, 30 patients with tuberculosis
      and 15 patients with other diseases (as the control samples) in Shanghai
      Pulmonary Hospital from January 1998 to December 2003. Lung tissues from 15
      normal embryonic mice served as the negative control. RESULTS: The positive rate
      of mycobacterial DNA in the tuberculosis samples (30/30) was higher than that of
      the sarcoidosis samples (6/31) and of the control samples (2/15). The difference
      between sarcoidosis and normal samples showed no statistical significance. The
      absolute and relative copies of mycobacterial DNA in the tuberculosis samples
      were significantly higher than those in the sarcoidosis and the control samples;
      while there was no statistical difference between the sarcoidosis and the control
      samples. There was no positive result in the lung tissues of the embryonic mice.
      CONCLUSIONS: The results do not show any relationship between mycobacterial
      infection and sarcoidosis. Quantitative PCR may be a reliable method for the
      differentiation of sarcoidosis from tuberculosis.

PMID- 18070556
TI  - [The pathologic significance and ionic mechanism of injured airway epithelium
      induced transdifferentiation of airway fibroblasts].
AB  - OBJECTIVE: To investigate the effects of injured airway epithelial cells on the
      transdifferentiation of sub-epithelial fibroblasts, thus addressing the
      mechanisms of characteristic airway remodeling in asthmatic airway. METHODS:
      Human sub-epithelial fibroblasts (SEF) or SEF in collagen gels were co-cultured
      with culture dishes which containing or not containing bronchial epithelial cells
      (16HBE) for 4 days. The experiments were divided into 7 groups according to
      different treatment to 16HBE; Group A: culture dishes not containing 16HBE; Group
      B: culture dishes containing normal 16HBE; Group C: culture dishes containing
      16HBE treated with mechanical scrape; Group D: culture dishes containing 16HBE
      treated with mechanical scrape plus LPS stimulation; Group E: culture dishes
      containing 16HBE pre-added with endothelin receptor A inhibitor (BQ123) followed
      by treatment with mechanical scrape plus LPS stimulation; Group F: culture dishes
      containing 16HBE pre-added with TGF-beta(1) neutralizing antibody followed by
      treatment with mechanical scrape plus LPS stimulation; Group G: culture dishes
      containing 16HBE pre-added with BQ123 plus TGF-beta(1) neutralizing antibody
      followed by treatment with mechanical scrape plus LPS stimulation. The expression
      of alpha-smooth muscle actin (alpha-SMA) in the SEF was assessed by
      immunofluorescence or Western blotting. The diameters of the collagen gels
      containing SEF (8 samples in each group) were measured. Moreover, SEF in group A,
      B or D were selected, and the dynamic changes of intracellular calcium
      concentration [Ca(2+)]i were observed (at least 6 cells were analyzed in each
      group) by laser co-focal microscopy in the transdifferentiated SEF in response to
      the stimulation of the supernatant of 16HBE treated with mechanical scrape plus
      LPS stimulation for 24 h. RESULTS: alpha-SMA expression in SEF was most abundant
      in group D compared with other groups. Relative contraction percentage was also
      significantly higher in group D [(53 +/- 8)%] than that in group B [(10 +/-
      10)%], group C [(24 +/- 8)%], group E [(36 +/- 9)%], group F [(37 +/- 3)%] or
      group G [(31 +/- 7)%], respectively (F = 24.80, 38.10, all P < 0.01). Increased
      fluorescence intensity of [Ca(2+)]i was observed in the SEF stimulated with the
      supernatant of the injured 16HBE in all groups, which was significant in group D
      (F = 16.60, 8.97; all P < 0.01). CONCLUSIONS: Injured airway epithelial cells
      induced the transdifferentiation of SEF towards alpha-SMA-expressing and elevated
      contractile myofibroblasts, in which both ET-1 and TGF-beta(1) may play crucial
      roles. The supernatant of injured airway epithelial cells-induced influx of
      [Ca(2+)]i may be an early signal for initiating the increased contractility in
      the transdifferentiated SEF.

PMID- 18070557
TI  - [Current combination drug therapy in the management of pulmonary artery
      hypertension].

PMID- 18070558
TI  - [The clinical application of six-minute walking test in chronic obstructive
      pulmonary disease].

PMID- 18070568
TI  - Non clinical careers for medical graduates.

PMID- 18070569
TI  - Histological grading patterns in patients of cutaneous leishmaniasis.
AB  - OBJECTIVE: To determine the histological grading patterns in a cohort of
      hospitalized patients of cutaneous leishmaniasis. DESIGN: Case series. PLACE AND
      DURATION OF STUDY: The study was conducted at PNS Shifa Hospital, Karachi, from
      May 2004 to June 2006. PATIENTS AND METHODS: One hundred patients of Cutaneous
      Leishmaniasis (CL), admitted in dermatology wards at PNS Shifa Hospital, Karachi,
      were examined. Only admitted patients of all ages and both sexes were included in
      the study. Patients of CL, who had received or were receiving systemic treatment
      were excluded. The lesions having marked secondary bacterial infection were also
      excluded. Initial diagnosis was clinical. History of being to an endemic area
      supported the diagnosis. The lesions were divided in two groups. Early, with
      duration less than 03 months and late, with duration between 3 and 12 months. The
      clinical lesions were noted as nodules, plaques, ulcers, crusted ulcers, lupoid
      lesions and plaques with scarring. Three types of skin smears (slit skin smear,
      saline aspirate smear and dab smear) were taken and examined with Giemsa stain.
      Cultures were performed on Nicolle-Novy-MacNeal (NNN) culture medium from Defense
      Scientific and Technology Organization (DESTO) Lab., Pakistan. Incisional skin
      biopsies were done. The biopsy specimens were examined by hemotoxylin and eosin
      stain (H & E stain). The number of Leishmania Tropica (LT) bodies was graded
      according to modified Ridley's parasitic index 1983. Clinical features were
      correlated with the histological patterns. RESULTS: Five histological patterns
      were identified in current study: 1) diffuse dermal infiltration without
      necrosis, 2) patchy dermal infiltration, 3) diffuse dermal infiltration with
      necrosis, 4) early reactive granuloma formation and 5) established epithelioid
      granuloma formation. LT bodies were identified in 75% of cases. Epidermal
      features were non-specific. The early lesions presented with diffuse infiltrate
      and late lesions showed granuloma formation. CONCLUSION: Five distinct types of
      histological patterns of CL have been recognized in this study. The early lesions
      presented with diffuse infiltrate and late lesions showed granuloma formation but
      the mixed patterns were also seen. The yield of LT bodies is much higher with
      histopathology as compared to skin smears and hence is most diagnostic.

PMID- 18070570
TI  - Sonographically determined clues to the symptomatic or silent cholelithiasis.
AB  - OBJECTIVE: To determine an association between sonographically determined
      contractility with the symptomatic or silent nature of gallstone. Designing:
      Comparative, cross-sectional study. PLACE AND DURATION OF STUDY: Radiology
      Department, Dow University of Health Sciences (DUHS) and Civil Hospital, Karachi
      (CHK), from April 2004 to March 2005. PATIENTS AND METHODS: Adult gallstone
      patients without (group I) and with biliary symptoms (group II) were compared
      with age and gender-matched controls. Demographic data, body mass index, risk
      factors, size, number and mobility of gallstone, gallbladder wall thickness
      (GBWT), volume and Ejection Fraction (EF) were determined on ultrasound before
      and after a standardized fatty meal (BFM and AFM). Demographic data, risk factors
      and gallstone characteristics were analyzed by Pearson Chi-square test and the
      gallbladder characteristics were analyzed by One-way ANOVA and Post Hoc tests by
      multiple comparisons on SPSS 11 with significance p=0.05. RESULTS: The
      gallbladder contractility as measured by changes in wall thickness and volume
      changes BFM and AFM, and ejection fraction was similar in controls and
      asymptomatic cholelithiasis groups and significantly reduced in symptomatic
      patients (p < .001). Multiparity (p=0.002), female gender (p=0.018), age less
      than 50 years (0.05), impacted calculi (p=0.001), multiple calculi (< .001) and
      calculi 5mm (p < 0.001) were associated with pain. CONCLUSION: A sluggishly
      emptying gallbladder was more significantly associated with symptomatic
      cholelithiasis compared to controls and asymptomatic cholelithiasis state in this
      series. Consideration of age, gender, impaction of calculi, number and size of
      calculi is important in causing symptom state and management options.

PMID- 18070571
TI  - Thymoma : a clinicopathologic association of world health organization histologic
      subtype and invasive behaviour.
AB  - OBJECTIVE: To re-classify thymic epithelial neoplasms reported at Aga Khan
      University Hospital during the past seven years according to the revised WHO
      classification, to assess the ease of application and determine association
      between WHO histological subtype and invasive behaviour. DESIGN: Descriptive
      study. PLACE AND DURATION OF STUDY: The study was carried out in the section of
      Histopathology, Department of Pathology and Microbiology, Aga Khan University
      Hospital, Karachi, from January 2000 to October 2006. MATERIAL AND METHODS: All
      cases of thymic epithelial neoplasms reported in the past seven years were
      retrieved using SNOMED coding system. Small biopsies where the tissue was
      insufficient for definite classification were not included. All cases were
      reviewed and reclassified according to WHO classification into types A, AB, B1,
      B2 and B3. Capsular invasion as well as extension into neighboring structures
      such as perithymic fat, pleura, pericardium, lung etc. was noted on morphology.
      RESULTS: A total of 62 cases were diagnosed as Thymic Epithelial Tumors (TET).
      Out of these, there were 5 type A (6 %), 17 type AB (21%), 7 type B1 (8.6%), 26
      type B2 (32%) and 7 type B3 (8.6%) thymomas. Age range was from 22-78 years with
      a median age of 46 years. Male to female ratio was 6:1. History of associated
      myasthenia gravis was present in 21% of cases. A significant association was
      observed between WHO histologic subtype and invasive behaviour where types A, AB
      and B1 have lesser number of invasive cases as compared to non-invasive, whereas
      in types B2 and B3, more cases have shown invasion as compared to non-invasive
      cases (c2 = 14.093, df =1, p-value < 0.001 ). CONCLUSION: The WHO classification
      is simple and easy to apply and has significant association with aggressive
      behavior. To some extent, it reflects the clinical behaviour of thymomas along
      with stage and status of resection. However, morphologically benign looking
      thymomas can behave aggressively. Hence, tumour stage, extent of resection and
      histology should be combined to predict the clinical behaviour of thymomas.

PMID- 18070572
TI  - Acute porphyrias: clinical spectrum of hospitalized patients.
AB  - OBJECTIVE: To determine characteristics, clinical features and triggers of acute
      porphyria in hospitalized patients presenting to a tertiary care center in
      Pakistan. DESIGN: Case series. PLACE AND DURATION OF STUDY: The Aga Khan
      University Hospital, Karachi, from 1988 to 2003. PATIENTS AND METHODS: Case
      records of 26 patients hospitalized with diagnosis were identified through
      computerized hospital patients' data. The diagnosis of acute porphyria was based
      on pertinent clinical features and laboratory investigations after exclusion of
      other alternative diagnosis and patients previously diagnosed as porphyric. The
      data was analyzed through SPSS software version 11.0. RESULTS: Twelve patients
      (46.2%) were males. Mean age was 21 years. Most common manifestation were
      gastrointestinal (n=22; 88.5%) followed by neurological symptoms (n=14; 54%).
      Neurological manifestations included seizures (n=9; 34.6%) and neuropathy (n=6;
      23%). One patient presented with depression and insomnia. Family history was
      positive in (n=8; 30.8%). Eighteen (69%) had history of previous attacks at their
      presentation to the hospital. Most common precipitating factor was 'eating
      outside' (n=18; 69%). CONCLUSION: Porphyrias are uncommon and cryptic group of
      diseases. This study shows a slightly different gender distribution, earlier
      onset of symptoms, higher number of neuropsychiatric symptoms (especially
      seizures), more distal neuropathies and different precipitant in the studied
      subset of patients than described previously in the western studies.

PMID- 18070573
TI  - COMPARISON OF DIFFERENT PHENOTYPIC METHODS OF DETECTION OF METHICILLIN RESISTANCE
      IN Staphylococcus aureus WITH THE MOLECULAR DETECTION OF mec-A GENE.
AB  - OBJECTIVE: To evaluate accuracy, cost-effectiveness and ease to perform different
      phenotypic methods i.e. Cefoxitin 30 microg disc, Oxacillin 1microg disc and
      Oxacillin agar screening plate (6microg/ml ) for early and accurate
      identification of MRSA by comparing with the detection of mec-A gene in our
      clinical isolates. DESIGN: A comparative study. PLACE AND DURATION OF STUDY:
      Clinical samples submitted in the Clinical Microbiology Laboratory at Aga Khan
      University Hospital, Karachi, from 1st August to 31st October 2006. MATERIAL AND
      METHODS: Out of 200 clinical samples, conventional Polymerase chain reaction
      (PCR) was done on 62 pure biochemically identified S. aureus isolates for mec-A
      gene detection. Phenotypic methods for detecting methicillin sensitivity
      (Cefoxitin 30 microg disc, Oxacillin 1 microg disc and Oxacillin agar screening
      plate) were also used according to the recommended incubation time, duration and
      temperature on the same isolates. RESULTS: Out of 62 isolates of S. aureus, mec-A
      gene were detected (MRSA) in 32, whereas 30 were mec-A gene negative (MSSA).
      Cefoxitin disc and agar screening plate correctly identify all MRSA isolates with
      the sensitivity and specificity of 100%. Single isolate was false, positively
      detected as sensitive with Oxacillin 1microg disc, due to which, the sensitivity
      and negative predictive value of this method were reduced to 96.9% and 96.8%
      respectively, while positive predictive value and specificity remained 100%.
      CONCLUSION: Comparing different phenotypic methods for MRSA screening in routine
      microbiology laboratory, Cefoxitin disc and Oxacillin agar screening has better
      sensitivity and specificity comparative to Oxacillin disc. However, Cefoxitin
      disc can be preferred especially for small laboratories because it is easy to
      perform, do not require special technique and media preparation is consequently
      more cost-effective.

PMID- 18070574
TI  - Referral pattern fof hemodialysis patients to nephrologists.
AB  - OBJECTIVE: To determine the referral pattern of dialysis patients to
      nephrologists and the effects of late referral on clinical, hematological and
      biochemical parameters in patients presenting for the first-time to dialysis
      center. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION: Hemodialysis
      Unit of Shalamar Hospital, Lahore, from June 2003 to October 2006. PATIENTS AND
      METHODS: This study was conducted on all patients of end stage renal diseases
      presenting for the first-time for undergoing hemodialysis at our center. Patients
      with acute renal failure were excluded from the study. At presentation, a history
      was taken from all the patients regarding seeking of nephrology services and
      referral pattern. Early and late referral was defined as the time of first
      referral or admission to a nephrologists greater or less than six months
      respectively before initiation of hemodialysis. All the patients were examined
      and their blood sample was drawn at the same time for routine hematological,
      biochemical parameters (urea, creatinine, serum potassium, calcium, phosphate and
      albumin) and viral markers (Anti HCV and HbsAg). RESULTS: In this study, 248
      patients were enrolled, amongst them, 131 (52.8%) were male and 117 (47.2%) were
      female. Major causes of renal failure were diabetes mellitus, chronic
      glomerulonephritis and hypertension. Most of the patients were euvolemic and
      hypertensive. Sixty percent of patients were having very high urea ( > 200 mg/dl)
      and creatinine ( > 8.0 mg/dl). Most of the patients, 226 (91.1%), were anemic
      (Hemoglobin < 11gm/dl) and 224(90%) were hypoalbuminemic (serum albumin<4gm/dl)
      on first presentation. Majority of patients were hyperkalemic, 139 (56.0%),
      hypocalcemic, 168 (67.7%) and serum phosphate level was high in only 117 (47%)
      patients. CONCLUSION: All the patients presented in emergency room to
      nephrologists at very late stage (100% late referral), when disease was very much
      advanced. All of them did not have permanent vascular access for hemodialysis on
      first presentation to dialysis center. Reasons for late referral were non
      availability of nephrologists and nephrology services, non-renal doctors biased,
      unawareness and training of medical professionals for these patients, patients'
      own denial for dialysis, fear and wrong perception about dialysis procedure,
      socioeconomic factors and use of non-evidenced based treatment modalities.

PMID- 18070575
TI  - Comparison of elective lumbar discectomy outcomes between civilians and military
      personnel.
AB  - OBJECTIVE: To determine the results of discectomy surgery for lumbar disc
      herniation in military personnel and compare it with civilians. DESIGN: A cross
      sectional study. PLACE AND DURATION: This study was conducted in Neurosurgery
      Department and Trauma Research Center, Baqiyatallah Medical Sciences University,
      Tehran, Iran, from February to October 2006. PATIENTS AND METHODS: One-hundred
      and seventeen military patients (54 subjects as combat forces and 63 as office
      personnel) and 115 civilians, who underwent discectomy surgery were included. In
      a mean duration of 50.8 months, the ability to return to full duty and resolution
      of complaints were assessed and satisfaction was measured using a Visual Analog
      Scale. RESULTS: Inability to return to previous duty was significantly higher in
      military personnel compared to civilians (p = 0.002); and in combat forces
      compared to office personnel (p < 0.001). The mean (SD) satisfaction was 80.09
      (17.8) and 79.32 (9.8) percent in civilian and military personnel, respectively;
      p = 0.02. However, this difference was not seen in military subgroup forces.
      Military personnel had less complaints after surgery, 32.1% comparing to 42.7% in
      civilians; but the difference was not statistically significant. Likewise, fewer
      complaints were observed in combat forces comparing with office forces; 37% vs.
      47.6% (p>0.05). CONCLUSION: Surgical intervention had relatively poor outcomes in
      military personnel, specifically in combat forces. Prevention of injury to back
      region should be considered in military training programs and in case of presence
      of disc herniation related symptoms, efforts should be made to save patients'
      effective function by conservation and medical therapies.

PMID- 18070576
TI  - Frequency and causes of bilateral occular trauma.
AB  - OBJECTIVE: To determine the frequency and causes of bilateral ocular trauma.
      DESIGN: A descriptive case series. PLACE AND DURATION OF STUDY: Khyber Institute
      of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar from October
      1999 to September 2006. PATIENTS AND METHODS: All patients coming to the hospital
      with bilateral eye trauma and requiring admission were recruited into the study.
      The details of patients' demographics, risk factors, ocular examination,
      treatment offered and final visual acuity were noted and described as frequency
      and percentages. RESULTS: Out of a total of 1551 patients of hospitalized ocular
      trauma, 46 (2.9%, 92 eyes) had bilateral ocular trauma. The majority (54.3%) were
      due to landmine blast injuries followed by dynamite blast in 10.8%, coalmine
      blast and firearm injury in 6.5% each. Pressure cooker explosion and road traffic
      accident was the cause in 4.3% each. Gas cylinder and automobile battery
      explosion, alkali and acid burn, assault and incidental trauma occurred in 2.1%.
      Sixty three percent were between 16 and 40 years of age. Males were affected in
      93.4%. Corneal and / or scleral repair was done in 58.6%, conjunctival and or
      corneal foreign body removal in 26% and extracapular cataract extraction with
      intraocular lens implantation in 16.3%. The visual acuity was in the range of
      6/60 and perception of light in 54.3%, while in 21.7%, there was no perception of
      light at the time of admission. Due to severity of injury, the final visual
      acuity was poor and only 28.2% regained vision between 6/18 and 6/60. CONCLUSION:
      In this series, landmine, dynamite and coalmine blasts were the major causes of
      bilateral ocular trauma. Victims were usually young males. Due to severity of
      ocular trauma, majority had poor visual outcome.

PMID- 18070577
TI  - Surgical management of hyperparathyroidism.
AB  - OBJECTIVE: To determine the efficacy of focused parathyroidectomy for adenoma and
      total parathyroidectomy with forearm autotransplantation for hyperplasia in
      maintaining serum calcium levels. STUDY DESIGN: Observational case series. PLACE
      AND DURATION OF STUDY: Department of General Surgery (Ward-2), Jinnah
      Postgraduate Medical Centre, Karachi, from January, 2002 to December, 2004.
      PATIENTS AND METHODS: Sixteen patients were admitted in this time period. Eleven
      of these patients had primary hyperparathyroidism and 4 had secondary
      hyperparathyroidism due to chronic renal failure. Pre-operative localization was
      done with Sestamibi scan and ultrasound of neck while methylene blue was used for
      intra-operative localization. All patients with primary hyperparathyroidism had
      single gland disease and were treated with focused parathyroidectomy. In 4
      patients with parathyroid hyperplasia, total parathyroidectomy with forearm
      autotransplantation was done. RESULTS: In the postoperative period, 3 patients
      developed hypocalcemia but they were managed on oral calcium and vitamin-D
      supplements. All of the remaining patients became normocalcaemic and there were
      no major complications. Mean hospital stay was 7-days. CONCLUSION: Focused
      parathyroidectomy for single gland disease and total parathyroidectomy with
      forearm auto-transplantation for hyperplasia was a satisfactory treatment for
      patients in this series.

PMID- 18070578
TI  - Pseudoxanthoma elasticum and nephrolithiasis: a rare association.
AB  - Pseudoxanthoma elasticum (PXE) is a multi-systemic, genetic disorder of
      connective tissue characterized by progressive calcification and fragmentation of
      elastic fibers in skin, retina and cardiovascular system. A young patient
      reported to urologist in emergency with azotemia secondary to acute bilateral
      obstructive uropathy. Upon successful management, he was found to have full-blown
      skin and eye manifestations and was evaluated thoroughly regarding extent and
      potential systemic complications of Pseudoxanthoma elasticum.

PMID- 18070579
TI  - Secondary syphilis lesions resembling pityriasis lichenoides.
AB  - This case report describes a male patient who presented with generalized,
      centrally-ulcerated papules with crusts and hypopigmented macules. Initially,
      differential diagnostic considerations included pityriasis lichenoides but the
      serology for syphilis was positive and there was a rapid response to penicillin
      with clearing of the lesions at the end of three weeks treatment.

PMID- 18070580
TI  - Acardiac twins: a case series.
AB  - Acardiac twinning is a severe and rare complication of monochorionic
      placentation. The acardiac twin does not survive while mortality of the normal
      twin is about 50-70% as the normal twin has to provide circulation not only for
      itself but also for acardiac twin. Proper timing of the delivery is of prime
      importance to the survival of the normal fetus for which emphasis is placed on
      close sonographic monitoring for early antenatal diagnosis. This series describes
      three such cases, which are now termed Twin Reversed Arterial Perfusion (TRAP)
      sequence.

PMID- 18070581
TI  - Adrenocortical carcinoma with endocrine syndromes.
AB  - Adrenocortical carcinoma is a rare disease. A 32 years old lady presented with
      complaints of hypertension, abdominal swelling, weight gain, hirsutism and bone
      pains. She was found to have a large adrenocortical carcinoma with associated
      Cushing's and virilization syndromes. Radical adrenalectomy was done with
      subsequent plan for Mitotane and radio frequency ablation for hepatic metastasis.
      However, she succumbed to respiratory failure due to ARDS, a month after
      operation.

PMID- 18070582
TI  - True malignant mixed tumor of parotid.
AB  - Carcinosarcoma is a rare malignant neoplasm of salivary glands that manifests
      both carcinomatous and sarcomatous components. Specimen of a recurrent parotid
      tumor of a 55-year-old male was received for histopathology. Diagnosis of a
      biphasic malignant neoplasm was made. Morphology and immunohistochemical profile
      were consistent with carcinosarcoma i.e. true malignant mixed tumor.

PMID- 18070583
TI  - Fatal aortoesophageal fistula resulting from ingestion of chicken bone.
AB  - A 22-year-old soldier was admitted in Combined Military Hospital, Attock, with
      dysphagia, chest pain and haemetemesis after swallowing a chicken bone during the
      dinner. The symptoms relieved spontaneously next day. The chest x-ray on the day
      of admission raised possibility of a radiopaque foreign body in the lower
      oesophagus. Repeat x-ray of chest and Barium swallow on next day did not reveal
      any radiopaque shadow, filling defect or leakage. He was discharged after 3 days
      of observation, during which, he remained asymptomatic. Nine days later, he was
      re-admitted in Combined Military Hospital, Multan, with massive haemetemesis. The
      endoscopy was inconclusive as stomach was full of blood clots. Laparotomy
      revealed triangular piece of chicken bone in the stomach associated with bleeding
      gastric erosions. The bleeding sites were stitched and cauterized.
      Postoperatively, he complained of pain in the left side of chest associated with
      breathlessness. X-ray of chest and ultrasound examination showed fluid collection
      in the pleural cavity. On chest intubation, 500 ml of blood stained fluid was
      drained. There was no haemetemesis in the postoperative period and gastric
      aspirate remained clear. One week later, he had massive haemetemesis, went into
      cardiac arrest and expired. Postmortem examination showed the cause of death to
      be aortoesophageal fistula.

PMID- 18070584
TI  - Vesical endometriosis.
AB  - Endometriosis affecting the urinary tract is very rare and the most common site
      of involvement is urinary bladder. The clinical features are urgency and
      frequency, hypo gastric pain and hematuria. Cystoscopic examination is the most
      valuable diagnostic test but definitive diagnosis requires histological
      confirmation. A 21-year-old unmarried female presented with lower urinary tract
      symptoms and blood in urine, more during menstruation. She gave history of left
      salpingo-oophorectomy. Ultrasonography revealed a mass in the bladder 2 x 3 cm on
      the posterior wall. Intravenous urography showed a filling defect in the bladder.
      Urethrocystoscopy performed and growth was resected and sent for histopathology.
      Histopathology confirmed the diagnosis of vesical endometriosis. She was advised
      Luteinizing hormone-releasing hormone (LHRH) but she refused as she could not
      afford it. She was managed on Tab 17-aethinyl testosterone.

PMID- 18070585
TI  - Fibromuscular dysplasia of renal arteries.
AB  - This case reports a young child having uncontrolled hypertension, resulting from
      bilateral renal artery stenosis due to fibromuscular dysplasia presenting with
      abdominal pain, headache and visual disturbance. Diagnostic features and
      management is discussed.

PMID- 18070586
TI  - Tuberous sclerosis with bilateral renal angiomyolipoma and wunderlich's syndrome.
AB  - This case describes a 47-year-old female with tuberous sclerosis associated with
      bilateral giant renal angiomyolipomas. She underwent an initial renal
      angioembolization in August 2006. After four months, she required emergency
      nephrectomy due to spontaneous hemorrhage from the angiomyolipoma (Wunderlich's
      syndrome). Life threatening Wunderlich's syndrome requires emergency nephrectomy,
      however, renal preservation can be achieved by elective nephron sparing surgery.

PMID- 18070587
TI  - Concomitant urothelial carcinoma and prostatic adenocarcinoma.

PMID- 18070588
TI  - Commentary on "oral stereognostic ability: a test of oral perception".

PMID- 18070589
TI  - LOCALIZATION OF A PARATHYROID ADENOMA IN A MULTI-NODULAR GOITER USING SESTAMIBI
      AND Tc-99m PERTECHNETATE SCANS.

PMID- 18070590
TI  - Effect of lysophosphatidylcholine on the surface hydration of phospholipid
      vesicles.
AB  - The interfacial properties of the negatively charged dimyristoyl
      phosphatidylglycerol (DMPG) and the zwitterionic dimyristoyl-phosphatidylcholine
      (DMPC) vesicles mixed with the fusion inhibitor lysomyristoylphosphatidylcholine
      (LMPC) are investigated by electron paramagnetic resonance (EPR). At 35 degrees
      C, addition of 20 mol% of LMPC to the DMPG vesicles increases the effective
      concentration of water in the interfacial layer of DMPG vesicles from 19.3 M to
      27.7 M, whereas in the case of mixed DMPC-LMPC vesicle the effective water
      concentration in the interfacial layer of DMPC vesicles only changes from 15.1 M
      to 18.4 M. The hydrogen bonding structure in both mixed DMPG-LMPC and mixed DMPC
      LMPC vesicles becomes stronger with an increasing fraction of LMPC in the
      vesicles. The average area per phospholipid decreases in mixed DMPC-LMPC
      vesicles, while it increases in mixed DMPG-LMPC vesicles as the proportion of
      LMPC in the vesicle increases. The inhibitory nature of LMPC in both vesicle and
      biological fusion comes from the increase in surface hydration, as well as from
      the dynamic cone shape of LMPC in the phospholipid bilayer.

PMID- 18070591
TI  - Role played by disabled-2 in albumin induced MAP Kinase signalling.
AB  - Albumin has been shown to activate the mitogen activated protein kinase (MAPK)
      pathway in proximal tubular cells (PTECs) of the kidney. Megalin, the putative
      receptor for albumin has potential signalling properties. However, the mechanisms
      by which megalin signals are unclear. The adaptor phosphoprotein Disabled-2
      (Dab2) is known to interact with the cytoplasmic tail of megalin and may be
      involved in albumin-mediated MAPK signalling. In this study, we investigated the
      role of Dab2 in albumin-mediated MAPK signalling and further studied the role of
      Dab2 in albumin-induced TGFbeta-1 secretion, a MAPK dependent event. We used RNA
      interference to knockdown Dab2 protein abundance in HKC-8 cells a model of human
      PTECs. Albumin activated ERK1,2 and Elk-1 in a MEK-1 dependent manner and
      resulted in secretion of TGFbeta-1. In the absence of albumin, knockdown of Dab2
      resulted in a trend towards increase in pERK1,2 consistent with its putative role
      as an inhibitor of cell proliferation. However albumin-induced ERK1,2 activation
      was completely abolished by Dab2 knockdown. Dab2 knockdown did not however result
      in inhibition of albumin-induced TGFbeta-1 secretion. These results suggest that
      Dab2 is a ligand dependent bi-directional regulator of ERK1,2 activity by
      demonstrating that in addition to its more traditional role as an inhibitor of
      ERK1,2 it may also activate ERK1,2.

PMID- 18070592
TI  - New evidence for cofactor's amino group function in thiamin catalysis by
      transketolase.
AB  - Transketolase from Saccharomyces cerevisiae exhibits a rarely reported activity
      with a methylated analogue of the native cofactor, 4'-methylamino-thiamin
      diphosphate. We demonstrated the kinetic stability of the dihydroxyethyl
      carbanion/enamine intermediate to be dependent on the functionality of the 4'
      aminopyrimidine moiety of thiamin diphosphate [R. Golbik, L.E. Meshalkina, T.
      Sandalova, K. Tittmann, E. Fiedler, H. Neef, S. Konig, R. Kluger, G.A. Kochetov,
      G. Schneider, G. Hubner, Effect of coenzyme modification on the structural and
      catalytic properties of wild-type transketolase and of the variant E418A from
      Saccharomyces cerevisae, FEBS J. (2005) 272 1326-1342]. This paper extends these
      investigations of the function of the coenzyme's aminopyrimidine in transketolase
      catalysis exemplified for the 4'-monomethylamino-thiamin diphosphate analogue.
      Here, we report near UV circular dichroism data and NMR-based analysis of
      reaction intermediates that give evidence for a strong destabilisation of the
      carbanion/enamine of DHE-4'-monomethylamino-thiamin diphosphate on the enzyme. A
      new negative band in near UV circular dichroism arising during turnover is
      attributed to the conjugate acid of the carbanion/enamine intermediate, an
      assignment additionally corroborated by (1)H NMR-based intermediate analysis. As
      opposed to the kinetically stabilized carbanion/enamine intermediate in
      transketolase when reconstituted with the native cofactor, DHE-4'-monomethylamino
      thiamin diphosphate is rapidly released from the active centers during turnover
      and accumulates in the medium on a preparative scale.

PMID- 18070593
TI  - RNA processing in Aquifex aeolicus involves RNase E/G and an RNase P-like
      activity.
AB  - To assess the evolutionary conservation of RNA processing pathways in Aquifex
      aeolicus, we characterized the products of rRNA and tRNA processing that
      originated from polycistronic transcripts encoded by the A. aeolicus tufA2 and
      rRNA operons. We found that, similar to its Escherichia coli counterpart, A.
      aeolicus RNase E/G is involved in rRNA processing and maturation of tRNAs, thus
      indicating that RNA processing pathways in E. coli and A. aeolicus include common
      steps and some of them are dependent on RNase E/G. Moreover, although recent
      biochemical approaches failed to detect an RNase P-like activity in A. aeolicus,
      our results suggest that such an activity exists in this organism. Accordingly,
      we show that this activity requires the presence of an RNA component and
      magnesium ions in order to be detectable in vitro and therefore shares common
      properties with bacterial RNase P.

PMID- 18070594
TI  - Role of modulator recognition factor 2 in adipogenesis and leptin expression in
      3T3-L1 cells.
AB  - The complex network of adipogenic transcription factors regulates adipocyte
      differentiation, obesity, and insulin resistance. Modulator recognition factor
      (Mrf) 2 knockout mice exhibit defects in fat accumulation and are protected from
      diet-induced obesity, suggesting that Mrf2 deficiency affects adipogenesis. Here,
      we report that the gene expressions of the 2 isoforms of the transcription
      factors Mrf2, Mrf2alpha, and Mrf2beta, were induced upon adipogenesis in 3T3-L1
      cells. Mrf2 mRNA expression was sensitive to stimulation by insulin,
      dexamethasone, and TNF-alpha in 3T3-L1 preadipocytes and differentiated
      adipocytes. Down-regulation of Mrf2alpha and Mrf2beta gene expressions induced by
      small interfering RNAs increased the mRNA expression of leptin. These results
      indicate that Mrf2 can be a potential regulator of adipocyte differentiation and
      a potential repressor of leptin.

PMID- 18070595
TI  - Memories of early work on muscle contraction and regulation in the 1950's and
      1960's.
AB  - Professor Ebashi's epic work on the biochemistry of the regulation of muscle
      contraction began in the early 1950's, during the same period that work on the
      molecular basis of force production in muscle was also beginning. The latter work
      started in two MRC Research Units in the UK, and was continued jointly by the two
      workers from those Units who had, independently, gone to MIT to learn the new
      techniques of electron microscopy and to apply them to muscle. In a somewhat
      similar fashion, Professor Ebashi also spent one or two years in the USA,
      continuing his work on the role of calcium in muscle regulation in Lippman's
      laboratory, before returning to Japan to achieve the great breakthroughs in this
      work during the 1960's. Hanson and Huxley, after putting forward the overlapping
      actin and myosin filament arrays model for the striated muscle sarcomere, and
      subsequently the sliding filament model of muscle contraction (simultaneously
      with A.F Huxley and R. Niedergerke), returned to the UK to pursue detailed
      structural studies in separate Research Units, in a mixture of consultation,
      collaboration, and competition, during the later 1950's and throughout the
      1960's. However, the path to enlightenment described here in some detail was
      somewhat more tortuous than the standard literature perhaps reveals.
      Nevertheless, by the time of the Cold Spring Harbor Symposium on Muscle
      Contraction in 1972, the two lines of enquiry on regulation itself, and on the
      tilting cross-bridge model of force production, had arrived at a good deal of
      common ground, and indeed the identification of troponin and its periodic
      distribution along the actin filaments had helped resolve a long-standing puzzle
      in the interpretation of the low angle X-ray diagram. Since then, an enormous
      amount of remarkable new work has been necessary to establish troponin regulation
      and the tilting cross-bridge mechanism in molecular detail, but the work in the
      1950's and 1960's has provided a firm and accurate basis for our current
      understanding.

PMID- 18070596
TI  - Inhibition of matrix metalloproteinase-9 gene expression by an isoflavone
      metabolite, irisolidone in U87MG human astroglioma cells.
AB  - Matrix metalloproteinase-9 (MMP-9) plays an important role in mediating the
      invasion and angiogenic process of malignant gliomas. This study was undertaken
      to determine if an isoflavone metabolite, irisolidone, inhibits MMP-9 expression
      in human astroglioma cells. Irisolidone was found to inhibit the secretion and
      protein expression of MMP-9 induced by PMA in U87 MG glioma cells, accompanied by
      the inhibition of MMP-9 mRNA expression and promoter activity. Further
      mechanistic studies revealed that irisolidone inhibits the binding of NF-kappaB
      and AP-1 to the MMP-9 promoter and suppresses the PMA-induced phosphorylation of
      ERK and JNK, which are upstream signaling molecules in MMP-9 expression. The
      Matrigel-invasion assay showed that irisolidone suppresses the in vitro
      invasiveness of glioma cells. Therefore, the strong inhibition of MMP-9
      expression by irisolidone might be a potential therapeutic modality for
      controlling the growth and invasiveness of gliomas.

PMID- 18070597
TI  - Direct monitoring of in vivo ER stress during the development of insulin
      resistance with ER stress-activated indicator transgenic mice.
AB  - Type 2 diabetes is one of the most prevalent and serious metabolic diseases in
      the world, and insulin resistance and pancreatic beta-cell dysfunction are the
      hallmarks of the disease. It has been suggested that endoplasmic reticulum (ER)
      stress is provoked under diabetic conditions and is possibly involved in the
      development of insulin resistance. In this study, using ER stress-activated
      indicator (ERAI) transgenic mice which express green fluorescent protein (GFP)
      under ER stress conditions, we directly monitored in vivo ER stress in various
      insulin target tissues such as liver, fat, and muscle in diabetic mice with
      insulin resistance induced by high fat and high sucrose (HF/HS) diet treatment.
      In the liver of the ERAI transgenic mice, ERAI fluorescence activity was clearly
      observed as early as after 4 weeks of HF/HS diet treatment, whereas it was not
      detected at all in the fat and muscle even after 12 weeks of HF/HS diet
      treatment. These results suggest that induction of ER stress is associated with
      the development of insulin resistance and that ER stress in the liver may
      facilitate the development of insulin resistance in the whole body. This is the
      first report to directly monitor in vivo ER stress in various insulin target
      tissues during the development of insulin resistance. In addition, our present
      results suggest that ERAI transgenic mice are very useful for evaluating in vivo
      ER stress, especially in the liver, during the development of insulin resistance.

PMID- 18070598
TI  - Role of UCH-L1/ubiquitin in acute testicular ischemia-reperfusion injury.
AB  - The most significant complication of testicular torsion is loss of the testis,
      which may lead to impaired fertility. Molecular mechanisms how spermatogenesis
      impairs owing to testicular torsion remain unknown. This investigation, by using
      mouse model of testicular torsion, was undertaken to gain insight into the
      cellular and molecular mechanism underlying torsion-induced germ cell loss. Male
      mice were subjected to 2h ischemia-inducing torsion, and testes were examined at
      24, 48, and 72h after the repair of torsion (reperfusion). Ischemia-reperfusion
      (IR) of the testes resulted in germ cell, mostly in spermatogonia, apoptosis,
      which was revealed by the terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) technique. At 24h
      after torsion repair germ cell apoptosis reached peak, then decreased until 72h
      repair. Western blots showed that apoptotic proteins (p53, Caspase-3 and -9)
      gradually were upregulated at 48h reperfusion, however, anti-apoptotic proteins
      (Bcl-2 and BDNF) were downregulated in the relevant IR treatment. IR injury
      induced CHOP protein appearance with maximum expression at 24h of reperfusion.
      Furthermore, the germ cell apoptosis triggered downregulation of ubiquitin
      carboxyl-terminal hydrolase-L1 (UCH-L1) at both mRNA and protein levels. To test
      further whether ubiquitination was involved in IR stress, both mono- and poly
      ubiquitin levels in IR stress condition were examined, which showed that both
      mono- and poly-ubiquitin expression significantly impaired. These results provide
      evidences of UCH-L1/ubiquitination signaling to the testis IR injury in vivo.

PMID- 18070599
TI  - Identification of p32 as a novel substrate for ATM in heart.
AB  - Chemotherapeutic agents to induce DNA damage have been limited to use due to
      severe side effects of cardiotoxicity. ATM (Ataxia-telangiectasia mutated) is an
      essential protein kinase in triggering DNA damage responses. However, it is
      unclear how the ATM-mediated DNA damage responses are involved in the cardiac
      cell damage. To elucidate these functions in heart, we searched for specific
      substrates of ATM from mouse heart homogenate. Combining an in vitro
      phosphorylation following anion-exchange chromatography with purification by
      reverse-phase high-performance liquid chromatography (HPLC), we successfully
      identified p32, an ASF/SF2-associated protein, as a novel substrate for ATM. An
      in vitro kinase assay using recombinant p32 revealed that ATM directly
      phosphorylated p32. Furthermore, we determined Ser 148 of p32 as an ATM
      phosphorylation site. Since p32 is known to regulate mRNA splicing and
      transcription, p32 phosphorylation by ATM might be a new transcriptional
      regulatory pathway for specific DNA damage responses in heart.

PMID- 18070600
TI  - Blood sampling and the measurement of circulating matrix metalloproteinase-8.

PMID- 18070601
TI  - Correlation between Shiga toxin B-subunit stability and antigen
      crosspresentation: a mutational analysis.
AB  - The homopentameric B-subunit of Shiga toxin (STxB) is used as a tool to deliver
      antigenic peptides and proteins to the cytosolic compartment of dendritic cells
      (DCs). In this study, a series of interface mutants of STxB has been constructed.
      All mutants retained their overall conformation, while a loss in thermal
      stability was observed. This effect was even more pronounced in trifluoroethanol
      solutions that mimic the membrane environment. Despite this, all mutants were
      equally efficient at delivering a model antigenic protein into the MHC class I
      restricted antigen presentation pathway of mouse DCs, suggesting that the
      structural stability of STxB is not a key factor in the membrane translocation
      process.

PMID- 18070602
TI  - The nucleoporin Nup358 associates with and regulates interphase microtubules.
AB  - The nucleoporin Nup358 resides on the cytoplasmic face of the interphase nuclear
      pore complex (NPC). During metaphase, its recruitment to kinetochores is
      important for correct microtubule-kinetochore attachment. Here, we report that a
      fraction of endogenous Nup358 interacts with interphase microtubules through its
      N-terminal region (BPN). Cells overexpressing the microtubule targeting domain of
      Nup358 displayed dramatic alteration in the microtubule organization including
      increased microtubule bundling and stability. Ectopic expression of BPN and full
      length Nup358 exhibited significantly higher levels of acetylated microtubules
      that were resistant to nocodazole, a microtubule depolymerizing agent.
      Furthermore, RNAi mediated depletion of Nup358 affected polarized stabilization
      of microtubules during directed cell migration, confirming the in vivo role of
      Nup358 in regulating interphase microtubules.

PMID- 18070603
TI  - Calmodulin interacts with angiotensin-converting enzyme-2 (ACE2) and inhibits
      shedding of its ectodomain.
AB  - Angiotensin-converting enzyme-2 (ACE2) is a regulatory protein of the renin
      angiotensin system (RAS) and a receptor for the causative agent of severe-acute
      respiratory syndrome (SARS), the SARS-coronavirus. We have previously shown that
      ACE2 can be shed from the cell surface in response to phorbol esters by a process
      involving TNF-alpha converting enzyme (TACE; ADAM17). In this study, we
      demonstrate that inhibitors of calmodulin also stimulate shedding of the ACE2
      ectodomain, a process at least partially mediated by a metalloproteinase. We also
      show that calmodulin associates with ACE2 and that this interaction is decreased
      by calmodulin inhibitors.

PMID- 18070604
TI  - Alternative mRNA splicing of SAP30L regulates its transcriptional repression
      activity.
AB  - Covalent modification of histones regulates chromatin structure and gene
      expression. Sin3A mediates the association of histone deacetylase enzymes with a
      large number of sequence-specific transcriptional repressors. In this study we
      characterized three novel transcripts of SAP30L, a recently identified Sin3A
      associated protein. These splice variants show significant differences in
      transcriptional repression capabilities and associating histone deacetylase
      activities. Furthermore, they differ in binding to Sin3A and in subcellular
      localization when transiently transfected. These data suggest that the
      transcriptional repression of a Sin3A corepressor complex can be regulated not
      only by sequence-specific transcriptional repressors, but also by modification of
      associated proteins, such as SAP30L.

PMID- 18070605
TI  - Differential splicing patterns of L-type calcium channel Cav1.2 subunit in hearts
      of Spontaneously Hypertensive Rats and Wistar Kyoto Rats.
AB  - Cav1.2 L-type calcium channels are essential in heart and smooth muscle
      contraction. Rat Cav1.2 gene contains 11 alternatively spliced exons (1a, 1, 8a,
      8, 9*, 21, 22, 31, 32, 32-6nt and 33) which can be assorted to generate a large
      number of functionally distinct splice variants. Until now, it is unknown whether
      the utilization of these alternatively spliced exons is altered in the
      hypertrophied hearts of hypertensive rats. By comparing the assortments of these
      11 exons in full-length Cav1.2 transcripts derived from Spontaneously
      Hypertensive Rats (SHRs) and Wistar Kyoto Rats (WKYs) hearts, we found that the
      inclusion of Cav1.2 alternative exons was significantly different between the two
      rats both at individual loci and in combinatorial arrangements. Functional
      characterizations of three Cav1.2 channel splice variants that were identified to
      be significantly altered in SHR hypertrophied cardiomyocytes demonstrated
      distinct whole-cell electrophysiological properties when expressed in HEK 293
      cells. Interestingly, aberrant splice variants which included or excluded both
      mutually exclusive exons 21/22 or exons 31/32 were found to be increased in
      hypertensive rats. Two aberrant splice variants that included both exons 21 and
      22 were found to be unable to conduct currents even though they expressed
      proteins with the predicted molecular mass. Characterization of one of the
      aberrant splice variants showed that it exerted a dominant negative effect on the
      functional Cav1.2 channels when co-expressed in HEK293 cells. The altered
      combinatorial splicing profiles of Cav1.2 transcripts identified in SHR hearts
      provide a different and new perspective in understanding the possible role of
      molecular remodeling of Cav1.2 channels in cardiac hypertrophy as a consequence
      of hypertension.

PMID- 18070606
TI  - The microtubule-associated protein tau is phosphorylated by Syk.
AB  - Aberrant phosphorylation of tau protein on serine and threonine residues has been
      shown to be critical in neurodegenerative disorders called tauopathies. An
      increasing amount of data suggest that tyrosine phosphorylation of tau might play
      an equally important role in pathology, with at least three putative tyrosine
      kinases of tau identified to date. It was recently shown that the tyrosine kinase
      Syk could efficiently phosphorylate alpha-synuclein, the aggregated protein found
      in Parkinson's disease and other synucleinopathies. We report herein that Syk is
      also a tau kinase, phosphorylating tau in vitro and in CHO cells when both
      proteins are expressed exogenously. In CHO cells, we have also demonstrated by co
      immunoprecipitation that Syk binds to tau. Finally, by site-directed mutagenesis
      substituting the tyrosine residues of tau with phenylalanine, we established that
      tyrosine 18 was the primary residue in tau phosphorylated by Syk. The
      identification of Syk as a common tyrosine kinase of both tau and alpha-synuclein
      may be of potential significance in neurodegenerative disorders and also in
      neuronal physiology. These results bring another clue to the intriguing overlaps
      between tauopathies and synucleinopathies and provide new insights into the role
      of Syk in neuronal physiology.

PMID- 18070607
TI  - Agonist-mediated docking of androgen receptor onto the mitotic chromatin platform
      discriminates intrinsic mode of action of prostate cancer drugs.
AB  - This study documents the analysis of a hitherto unreported dynamic behavior of
      androgen receptor (AR), a member of the nuclear receptor superfamily. Employing
      GFP-tagged AR, we observed agonist-mediated docking of AR onto the mitotic
      chromatin during all the stages of mitosis. When bound to therapeutic drugs with
      intrinsically absolute or partial agonistic properties, AR concomitantly
      associated with the mitotic chromatin. Conversely, pure antagonists known to bind
      and subsequently translocate unliganded AR from cytoplasm to nuclear compartment
      did not provoke such association. The agonist-mediated docking of AR could not be
      competed with other transcription factors that constitutively preoccupied the
      chromosomal docking sites. Amongst the previously reported proteins, AR is first
      example of a transcription factor whose response on mitotic chromatin platform
      can be modulated in a ligand-specific manner. However, data from live cell
      imaging revealed that co-activators of agonist-activated receptor that are
      recruited into "nuclear foci" of interphase chromatin are dislodged from the
      mitotic chromatin during cell division. This implies that in absence of critical
      co-activators, AR transverses mitotic phase in transcriptionally silenced state.
      Finally, our results indicate that ligand-mediated dynamic relationship of
      nuclear receptors with mitotic chromatin can be effectively exploited to study,
      analyze and authenticate therapeutic ligands.

PMID- 18070608
TI  - Function and redox state of mitochondrial localized cysteine-rich proteins
      important in the assembly of cytochrome c oxidase.
AB  - The cytochrome c oxidase (CcO) complex of the mitochondrial respiratory chain
      exists within the mitochondrial inner membrane (IM). The biogenesis of the
      complex is a multi-faceted process requiring multiple assembly factors that
      function on both faces of the IM. Formation of the two copper centers of CcO
      occurs within the intermembrane space (IMS) and is dependent on assembly factors
      with critical cysteinyl thiolates. Two classes of assembly factors exist, one
      group being soluble IMS proteins and the second class being proteins tethered to
      the IM. A common motif in the soluble assembly factors is a duplicated Cx(9)C
      sequence motif. Since mitochondrial respiration is a major source of reactive
      oxygen species, control of the redox state of mitochondrial proteins is an
      important process. This review documents the role of these cysteinyl CcO assembly
      factors within the IMS and the necessity of redox control in their function.

PMID- 18070609
TI  - Inhibition of phorbol ester-dependent peroxiredoxin I gene activation by
      lipopolysaccharide via phosphorylation of RelA/p65 at serine 276 in monocytes.
AB  - Peroxiredoxin I (Prx I) is an antioxidant enzyme with thioredoxin-dependent
      peroxidase activity which is involved in various cellular processes such as
      regulation of cell proliferation. Here, it is shown that the proinflammatory
      mediator lipopolysaccharide (LPS) inhibits the induction of Prx I expression and
      promoter activity by the phorbol ester 12-O-tetradecanoylphorbol- 13-acetate
      (TPA) in RAW264.7 monocytes, but not that of cyclooxygenase-2. LPS-dependent
      repression of Prx I induction by TPA was mediated via a newly identified kappaB
      site in the Prx I promoter, but the "classical" NF-kappaB cascade was not
      involved in this regulatory pathway, because IkappaB did not affect LPS-mediated
      Prx I repression. By contrast, phosphorylation of p65 at serine 276, which
      enhances the transcriptional activity of NF-kappaB, was up-regulated by TPA and
      was reduced by simultaneous exposure to LPS. Functional studies with Gal4-p65
      constructs revealed that serine 276 is crucial to confer LPS-dependent repression
      of TPA-mediated induction of p65 transactivation. Finally, repression of TPA
      dependent Prx I induction by LPS was mediated via Bruton's tyrosine kinase as
      indicated by studies with the pharmacological inhibitor LFM-A13. In summary, LPS
      dependent inhibition of Prx I gene activation by TPA in monocytes is regulated
      via a pathway that involves phosphorylation of the NF-kappaB subunit p65 at
      serine 276.

PMID- 18070610
TI  - Bilirubin inhibits Plasmodium falciparum growth through the generation of
      reactive oxygen species.
AB  - Free heme is very toxic because it generates highly reactive hydroxyl radicals
      ((.)OH) to cause oxidative damage. Detoxification of free heme by the heme
      oxygenase (HO) system is a very common phenomenon by which free heme is
      catabolized to form bilirubin as an end product. Interestingly, the malaria
      parasite, Plasmodium falciparum, lacks an HO system, but it forms hemozoin,
      mainly to detoxify free heme. Here, we report that bilirubin significantly
      induces oxidative stress in the parasite as evident from the increased formation
      of lipid peroxide, decrease in glutathione content, and increased formation of
      H(2)O(2) and (.)OH. Bilirubin can effectively inhibit hemozoin formation also.
      Furthermore, results indicate that bilirubin inhibits parasite growth and induces
      caspase-like protease activity, up-regulates the expression of apoptosis-related
      protein (Gene ID PFI0450c), and reduces the mitochondrial membrane potential.
      (.)OH scavengers such as mannitol, as well as the spin trap alpha-phenyl-n-tert
      butylnitrone, effectively protect the parasite from bilirubin-induced oxidative
      stress and growth inhibition. These findings suggest that bilirubin, through the
      development of oxidative stress, induces P. falciparum cell death and that the
      malaria parasite lacks an HO system probably to protect itself from bilirubin
      induced cell death as a second line of defense.

PMID- 18070611
TI  - Downregulation of Par-3 expression and disruption of Par complex integrity by TGF
      beta during the process of epithelial to mesenchymal transition in rat proximal
      epithelial cells.
AB  - Epithelial to mesenchymal transition (EMT) is a fundamental mechanism of organ
      fibrosis and the initial step is disruption of cell junction and cell polarity.
      TGF-beta has been demonstrated as the most important mediator of EMT which is
      sufficient to initiate and complete the whole course of EMT, however, the
      detailed mechanism of TGF-beta in modulating the disruption of cell junction
      still remains unclear. Par-3 is a component of Par complex which plays a crucial
      role in the establishment and maintenance of epithelial polarity. In this study,
      we found that TGF-beta treatment resulted in a dose- and time-dependent
      downregulation of Par-3 protein together with the suppression of E-cadherin
      expression and induction of alpha-SMA. The decreased Par-3 subsequently resulted
      in the redistribution of Par-6-aPKC complex from cell membrane to cytoplasm.
      Forced expression of exogenous Par-3 into rat proximal epithelial cells (NRK52E)
      led to a drastic blockage of TGF-beta1-induced E-cadherin suppression and alpha
      SMA induction. In contrast, knockdown Par-3 expression by siRNA significantly
      enhanced TGF-beta1-induced E-cadherin suppression and alpha-SMA induction. These
      data indicate that downregulation of Par-3 and subsequent disruption of Par
      complex integrity might be one mechanism that TGF-beta destroys cell polarity
      during EMT.

PMID- 18070612
TI  - The role of the noradrenergic system in emotional memory.
AB  - This contribution is an overview on the role of noradrenaline as neurotransmitter
      and stress hormone in emotional memory processing. The role of stress hormones in
      memory formation of healthy subjects can bear significance for the derailment of
      memory processes, for example, in post traumatic stress disorder (PTSD).
      Increased noradrenaline levels lead to better memory performance, whereas
      blocking the noradrenergic receptors with a betablocker attenuates this enhanced
      memory for emotional information. Noradrenaline appears to interact with cortisol
      in emotional memory processes, varying from encoding to consolidation and
      retrieval. Imaging studies show that confronting human subjects with emotional
      stimuli results in increased amygdala activation and that this activation is
      noradrenergic dependent. The role of noradrenaline in other brain areas, such as
      hippocampus and prefrontal cortex, is shortly summarized. Finally, the pros and
      cons of a therapeutic application of betablockers in the (secondary) prevention
      of PTSD will be discussed.

PMID- 18070613
TI  - Why do delayed summaries improve metacomprehension accuracy?
AB  - We showed that metacomprehension accuracy improved when participants (N=87
      college students) wrote summaries of texts prior to judging their comprehension;
      however, accuracy only improved when summaries were written after a delay, not
      when written immediately after reading. We evaluated two hypotheses proposed to
      account for this delayed-summarization effect (the accessibility hypothesis and
      the situation model hypothesis). The data suggest that participants based
      metacomprehension judgments more on the gist of texts when they generated
      summaries after a delay; whereas, they based judgments more on details when they
      generated summaries immediately after reading. Focusing on information relevant
      to the situation model of a text (the gist of a text) produced higher levels of
      metacomprehension accuracy, which is consistent with situation model hypothesis.

PMID- 18070614
TI  - Effects of sex hormones on genioglossal muscle contractility and SR Ca2+-ATPase
      activity in aged rat.
AB  - This investigation was designed to examine whether short-term administration of
      sex hormones could produce changes in contractile properties and the sarcoplasmic
      reticulum Ca(2+)-ATPase (SERCA) function in genioglossal muscle (GG) of aged male
      rats. Twenty-four aged male rats were randomly divided into three groups to
      receive an intramuscular injection of either 0.1mg/kg oestrogen (group A), 2.5
      mg/kg testosterone (group B), or 0.2 ml sterile peanut oil (group C, control),
      twice a week, during 4 weeks. After hormone treatment, in vivo isometric
      contractile properties were determined using surgically prepared GG muscles with
      platinum electrodes for stimulation of the medial branch of the hypoglossus
      nerve. Sarcoplasmic reticulum Ca(2+)-ATPase activity was measured in muscle
      homogenates by detecting the amount of inorganic phosphorus ion released in a
      standard coupled enzyme assay. SERCA1 mRNA level was observed using a real-time
      quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR). It was
      found that, compared with group C, testosterone treatment decreased the fatigue
      resistance in GG muscles (p<.05), whereas no change was observed in the isometric
      twitch (P(t)) and tetanic tension (P(0)) (p>.05). By contrast, in oestrogen
      treated GG muscles, no significant modification was found either in the
      contractile or in endurance properties (p>.05). The change in GG fatigue
      resistance of group B was associated with a marked decrease in SR Ca(2+)-ATPase
      activity when compared with that of the control group (p<.01). Furthermore,
      SERCA1 mRNA level was also down regulated in group B (p<.05). No prominent
      differences in SR Ca(2+)-ATPase activity and SERCA1 mRNA expression existed
      between group A and group C (p>.05). The present results show that exogenous
      testosterone produces more pronounced changes in GG muscle fatigue resistance
      than oestrogen does by acting at SR Ca(2+)-ATPase activity and SERCA gene
      expression.

PMID- 18070615
TI  - Effect of carboxymethylcellulose-based saliva substitutes on predemineralised
      dentin evaluated by microradiography.
AB  - OBJECTIVE: This study investigated the effect of six lab-produced saliva
      substitutes based on carboxymethylcellulose (CMC) differing in
      octacalciumphosphate saturations (OCP-s) on mineralisation of bovine dentin in
      vitro. DESIGN: Dentin specimens were prepared (n=234); prior to and after
      demineralisation (37 degrees C; pH 5.0; 7 d), one-third of each specimen surface
      was covered with nail varnish (control of sound dentin). Subsequently, specimens
      (n=13) were exposed to either one of the six CMC-based solutions (OCP-s: 0, 0.5,
      1, 2, 4, and 8) at pH 6.5 or to Glandosane for 5 and 10 weeks (37 degrees C). Two
      aqueous solutions (OCP-s: 0 and 1) served as controls. After storage, thin
      sections were prepared and mineral loss was calculated by transversal
      microradiography. RESULTS: After both storage periods specimens immersed in
      Glandosane revealed a significantly increased mineral loss compared to all other
      solutions (p<0.05; Bonferroni post hoc test). Control solution with OCP-s=1
      induced a significant remineralisation (p<0.05; adjusted paired t-test). Only
      after 5 weeks exposure to the CMC-based solution with an OCP-s=2 a significant
      remineralisation compared to baseline (p<0.05) as well as a significantly
      increased mineral gain of the surface area compared to higher saturated solutions
      (p<0.05; Bonferroni post hoc test) could be observed. CONCLUSIONS: CMC seems to
      hamper dentin remineralisation, although after 5 weeks a mineral gain could be
      induced with slightly supersaturated CMC-solutions with respect to OCP.

PMID- 18070616
TI  - Anti-inflammatory interventions of NF-kappaB signaling: potential applications
      and risks.
AB  - Signaling via NF-kappaB is a key process during inflammation and thus constitutes
      an attractive target for anti-inflammatory therapeutic interventions. Especially
      during initial hyperinflammatory states of an acute illness such as sepsis or in
      the course of chronic inflammation and autoimmune diseases inhibition of IKK
      driven NF-kappaB activation provides a promising treatment strategy. Given its
      critical role in innate and adaptive immune responses, however, there is a
      certain amount of risk due to induced immunodeficiency that may follow inhibitory
      treatment. Moreover, its primary anti-apoptotic function suggests that blockade
      of NF-kappaB activation has dramatic effects on cell functions and survival and
      eventually worsens the course of an inflammatory disease. An overview of
      canonical and alternative NF-kappaB activation and its critical role in immune
      responses will be provided. A main topic focuses on recent animal studies and
      data derived from genetic studies in humans that provide an insight into
      potential effects of different therapeutic modulations of NF-kappaB inflammatory
      signaling. The pros and cons of NF-kappaB inhibition and treatment strategies
      will be critically reviewed.

PMID- 18070617
TI  - Inhibition of glioblastoma growth and angiogenesis by gambogic acid: an in vitro
      and in vivo study.
AB  - Gambogic acid (GA) is the major active ingredient of gamboge, a brownish to
      orange resin exuded from Garcinia hanburryi tree in Southeast Asia. The present
      study aims to demonstrate that gambogic acid (GA) has potent anticancer activity
      for glioblastoma by in vitro and in vivo study. Rat brain microvascular
      endothelial cells (rBMEC) were used as an in vitro model of the blood-brain
      barrier (BBB). To reveal an involvement of the intrinsic mitochondrial pathway of
      apoptosis, the mitochondrial membrane potential and the western blot evaluation
      of Bax, Bcl-2, Caspase-3, caspase-9 and cytochrome c released from mitochondria
      were performed. Angiogenesis was detected by CD31 immunochemical study. The
      results showed that the uptake of GA by rBMEC was time-dependent, which indicated
      that it could pass BBB and represent a possible new target in glioma therapy. GA
      could cause apoptosis of rat C6 glioma cells in vitro in a concentration
      dependent manner by triggering the intrinsic mitochondrial pathway of apoptosis.
      In vivo study also revealed that i.v. injection of GA once a day for two weeks
      could significantly reduce tumor volumes by antiangiogenesis and apoptotic
      induction of glioma cells. Collectively, the current data indicated that GA may
      be of potential use in treatment of glioblastoma by apoptotic induction and
      antiangiogenic effects.

PMID- 18070618
TI  - Synthesis of flaccidoside II, a bidesmosidic triterpene saponin isolated from
      Chinese folk medicine Di Wu.
AB  - A total synthesis of flaccidoside II, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D
      xylopyranosyloleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D
      glucopyranosyl-(1-->6)-beta-D-glucopyranoside, isolated from Chinese folk
      medicine Di Wu, has been accomplished from building blocks isopropyl 2-O-acetyl
      3,4-di-O-benzoyl-1-thio-beta-D-xylopyranoside, 2,3,4-tri-O-benzoyl-alpha-L
      rhamnopyranosyl trichloroacetimidate, oleanolic acid trityl ester, ethyl 2,3-di-O
      acetyl-6-O-benzoyl-1-thio-beta-D-glucopyranoside and 4-methoxyphenyl 2,3,4-tri-O
      acetyl-beta-D-glucopyranoside. The use of a partially protected thioglycosyl
      donor significantly simplified the synthesis of the target saponin.

PMID- 18070619
TI  - New enzyme-based method for analysis of water-soluble wheat arabinoxylans.
AB  - Arabinoxylans (AX) are the predominant cell-wall polysaccharides in wheat flour.
      Water-extractable AX are essential for dough and bread properties and
      performance. However, there is no specific and accurate way of determining the
      content and structure of AX. An enzyme-assisted method employing an efficient
      enzyme mixture for the total hydrolysis of AX was developed in the present work.
      Enzymatic hydrolysis (EH) is a gentle method during which no unwanted sugar
      destruction occurs. Following EH, liberated monosaccharides were analysed by gas
      chromatography (GC) and liquid chromatography using HPAEC-PAD. The results were
      compared with acid methanolysis (AM) and acid hydrolysis (AH). EH performed
      better on commercially isolated AX samples than the reference method AM. Its
      action in the water extract from wheat flour was also more efficient than that of
      AM and comparable to the efficiency of AH. HPAEC-PAD revealed a significant
      amount of fructose in the water extract following EH, originating from fructans
      in wheat flour not detected in the GC analysis. The wheat flour examined
      contained 0.29% water-extractable AX. The arabinose/xylose ratio was 0.32. The
      enzyme-based method developed is applicable for comparison of different wheat
      flours and can be used in evaluating the effect of processing on the content and
      structure of water-extractable AX.

PMID- 18070621
TI  - Acoustic emphasis in four year olds.
AB  - Acoustic emphasis may convey a range of subtle discourse distinctions, yet little
      is known about how this complex ability develops in children. This paper presents
      a first investigation of the factors which influence the production of acoustic
      prominence in young children's spontaneous speech. In a production experiment,
      SVO sentences were elicited from 4 year olds who were asked to describe events in
      a video. Children were found to place more acoustic prominence both on 'new'
      words and on words that were 'given' but had shifted to a more accessible
      position within the discourse. This effect of accessibility concurs with recent
      studies of adult speech. We conclude that, by age four, children show
      appropriate, adult-like use of acoustic prominence, suggesting sensitivity to a
      variety of discourse distinctions.

PMID- 18070620
TI  - An essential oil and its major constituent isointermedeol induce apoptosis by
      increased expression of mitochondrial cytochrome c and apical death receptors in
      human leukaemia HL-60 cells.
AB  - An essential oil from a lemon grass variety of Cymbopogon flexuosus (CFO) and its
      major chemical constituent sesquiterpene isointermedeol (ISO) were investigated
      for their ability to induce apoptosis in human leukaemia HL-60 cells because
      dysregulation of apoptosis is the hallmark of cancer cells. CFO and ISO inhibited
      cell proliferation with 48 h IC50 of approximately 30 and 20 microg/ml,
      respectively. Both induced concentration dependent strong and early apoptosis as
      measured by various end-points, e.g. annexinV binding, DNA laddering, apoptotic
      bodies formation and an increase in hypo diploid sub-G0 DNA content during the
      early 6h period of study. This could be because of early surge in ROS formation
      with concurrent loss of mitochondrial membrane potential observed. Both CFO and
      ISO activated apical death receptors TNFR1, DR4 and caspase-8 activity.
      Simultaneously, both increased the expression of mitochondrial cytochrome c
      protein with its concomitant release to cytosol leading to caspase-9 activation,
      suggesting thereby the involvement of both the intrinsic and extrinsic pathways
      of apoptosis. Further, Bax translocation, and decrease in nuclear NF-kappaB
      expression predict multi-target effects of the essential oil and ISO while both
      appeared to follow similar signaling apoptosis pathways. The easy and abundant
      availability of the oil combined with its suggested mechanism of cytotoxicity
      make CFO highly useful in the development of anti-cancer therapeutics.

PMID- 18070623
TI  - Reliable identification of pesticides using linear retention indices as an active
      tool in gas chromatographic-mass spectrometric analysis.
AB  - The present research is focused on the current development and employment of a
      dedicated pesticide mass spectral library, characterized by a double-filter
      search procedure: the first is based on the degree of spectral similarity and the
      second on chromatographic retention information (linear retention indices). The
      highly pure mass spectra contained in the library have been attained by
      subjecting mixtures of widely used pesticides to comprehensive GC-MS analysis.
      Linear retention indices for conventional GC-MS analyses were calculated by
      injecting the same compounds on a single-column GC-MS system. The effectiveness
      of this approach was verified by analysing a white wine sample spiked with 10
      structurally similar pyrethroid compounds, through automated solid-phase
      microextraction-GC-MS.

PMID- 18070624
TI  - Ultra-performance liquid chromatographic analysis of amino acids in protein
      hydrolysates using an automated pre-column derivatisation method.
AB  - In the present study, the changeover from the Pico.Tag HPLC method to the
      AccQ.Tag(ultra) UPLC method for the analysis of amino acids in casein and bovine
      serum albumine hydrolysates is described. The total chromatographic run time of
      the AccQ.Tag(ultra) UPLC method was only 40% of the time required for the
      Pico.Tag HPLC method. Quantitative results of both methods for casein and bovine
      serum albumine hydrolysates compared fairly well. The derivatisation protocol for
      the formation of AQC derivatives of amino acids was automated using a Gilson
      Model 215 liquid handler. Comparison of the manual derivatisation protocol with
      the automated protocol showed lower coefficients of variation for the latter.
      Combination of the AccQ.Tag(ultra) UPLC method and automated derivatisation
      resulted in improved throughput compared to the Pico.Tag HPLC method.

PMID- 18070622
TI  - Protein kinase C epsilon activates lens mitochondrial cytochrome c oxidase
      subunit IV during hypoxia.
AB  - Protein kinase C (PKC) isoforms have been identified as major cellular signaling
      proteins that act directly in response to oxidation conditions. In retina and
      lens two isoforms of PKC respond to changes in oxidative stress, PKCgamma and
      PKCepsilon, while only PKCepsilon is found in heart. In heart the PKCepsilon acts
      on connexin 43 to protect from hypoxia. The presence of both isoforms in the lens
      led to this study to determine if lens PKCepsilon had unique targets. Both lens
      epithelial cells in culture and whole mouse lens were examined using PKC isoform
      specific enzyme activity assays, co-immunoprecipitation, confocal microscopy,
      immunoblots, and light and electron microscopy. PKCepsilon was found in lens
      epithelium and cortex but not in the nucleus of mouse lens. The PKCepsilon
      isoform was activated in both epithelium and whole lens by 5% oxygen when
      compared to activity at 21% oxygen. In hypoxic conditions (5% oxygen) the
      PKCepsilon co-immunoprecipitated with the mitochondrial cytochrome c oxidase IV
      subunit (CytCOx). Concomitant with this the CytCOx enzyme activity was elevated
      and increased co-localization of CytCOx with PCKvarepsilon was observed using
      immunolabeling and confocal microscopy. In contrast, no hypoxia-induced
      activation of CytCOx was observed in lenses from the PKCepsilon knockout mice.
      Lens from 6-week-old PKCepsilon knockout mice had a disorganized bow region which
      was filled with vacuoles indicating a possible loss of mitochondria but the size
      of the lens was not altered. Electron microscopy demonstrated that the nuclei of
      the PCKepsilon knockout mice were abnormal in shape. Thus, PKCepsilon is found to
      be activated by hypoxia and this results in the activation of the mitochondrial
      protein CytCOx. This could protect the lens from mitochondrial damage under the
      naturally hypoxic conditions observed in this tissue. Lens oxygen levels must
      remain low. Elevation of oxygen which occurs during vitreal detachment or
      liquification is associated with cataracts. We hypothesize that elevated oxygen
      could cause inhibition of PKCepsilon resulting in a loss of mitochondrial
      protection.

PMID- 18070625
TI  - Qualitative mass spectrometric analysis of the volatile fraction of creosote
      treated railway wood sleepers by using comprehensive two-dimensional gas
      chromatography.
AB  - The volatile composition of 20-year-old out-of-service creosote-treated railway
      wood sleepers was studied. The emitted volatile fraction was collected by means
      of dynamic purge-and-trap concentration at ambient temperature, and analyzed by
      comprehensive two-dimensional gas chromatography (GC x GC) hyphenated with mass
      spectrometric detection systems, using quadrupole (GC x GC/qMS) and time-of
      flight (GC x GC/ToF-MS) mass analyzers and selective nitrogen-phosphorus
      detection (GC x GC-NPD). The analysis of mass spectrometry data and GC x GC
      retention time allowed the tentative identification of about 300 compounds based
      on spectrometric data and positioning of each compound in the GC x GC plot. Major
      important headspace components are polyaromatic hydrocarbons, phenols and benzene
      derivatives, hydrocarbons and heterocyclic compounds containing nitrogen, sulphur
      or oxygen atoms. Many of the reported compounds are listed as belonging to
      toxicological substance classes which have been related to harmful health
      effects. GC x GC provides greater speciation and evidence of composition
      heterogenicity of the sample than one-dimensional GC analysis, thus allowing to
      better demonstrate its potential toxicity. Data obtained by specific detection
      systems for N-heterocycles assisted mass data interpretation assignments. The
      enhanced separation power obtained after GC x GC compared to one-dimensional gas
      chromatography (1D-GC) together with spectral deconvolution and correlation with
      physical-chemical data, allowed the identification of complex isomer clusters, as
      demonstrated for alkylquinolines, and applied also to alkylphenols, alkylbenzenes
      and alkylnaphthalenes.

PMID- 18070626
TI  - Supported liquid-liquid extraction of the active ingredient (3,4
      methylenedioxymethylamphetamine) from ecstasy tablets for isotopic analysis.
AB  - A method was developed for the isolation of 3,4-methylenedioxymethylamphetamine
      (MDMA) and other active ingredients from illicit ecstasy tablets. The method
      employed supported liquid extraction (SLE) with cartridges containing a modified
      form of diatomaceous earth. The method developed was simple and robust and the
      extract could be analysed directly, by GC-MS, to identify ingredients and reduced
      in volume for isotope ratio MS analysis of both delta(13)C and delta(15)N. The
      technique was shown to be highly reproducible, independent of the tablet matrix
      and considerably faster than existing liquid-liquid extraction methods.
      Crucially, no significant isotopic fractionation was observed as a result of the
      extraction process.

PMID- 18070627
TI  - Qualitative screening and quantitative determination of pesticides and
      contaminants in animal feed using comprehensive two-dimensional gas
      chromatography with time-of-flight mass spectrometry.
AB  - A method has been developed for the target analysis of over 100 pesticides and
      contaminants in a complex feed matrix. The method is based on extraction with
      ethyl acetate, cleanup by gel permeation chromatography (GPC) and dispersive
      solid-phase extraction (SPE) with primary secondary amine phase (PSA), and
      analysis by comprehensive two-dimensional gas chromatography with full scan time
      of-flight mass spectrometric detection (GC x GC-TOF-MS). Parameters studied
      during method development included a dispersive SPE cleanup step after GPC, large
      volume injection into the GC system and the GC x GC separation. Qualitative and
      quantitative performance of the GC x GC system was evaluated by analyzing spiked
      extracts in the range equivalent to 1-100 microg/kg in feed. At levels of 50
      microg/kg and higher, all compounds targeted for could be identified fully
      automatically by the software based on their mass spectra. At lower levels the
      hit rate decreased with the concentration. System linearity was excellent in
      solvent and only slightly affected by matrix (correlation coefficients r>or=0.995
      for 90% of the compounds). Limits of quantification were in the 1-20 microg/kg
      range for most compounds. The overall method was validated for 106 compounds at
      the 10 and 100 microg/kg level. Recoveries between 70% and 110% and RSDs below
      20% were obtained for the majority of the compounds.

PMID- 18070628
TI  - The kindergarten path effect revisited: children's use of context in processing
      structural ambiguities.
AB  - Research with adults has shown that ambiguous spoken sentences are resolved
      efficiently, exploiting multiple cues--including referential context--to select
      the intended meaning. Paradoxically, children appear to be insensitive to
      referential cues when resolving ambiguous sentences, relying instead on
      statistical properties intrinsic to the language such as verb biases. The
      possibility that children's insensitivity to referential context may be an
      artifact of the experimental design used in previous work was explored with 60 4-
      to 11-year-olds. An act-out task was designed to discourage children from making
      incorrect pragmatic inferences and to prevent premature and ballistic responses
      by enforcing delayed actions. Performance on this task was compared directly with
      the standard act-out task used in previous studies. The results suggest that
      young children (5 years) do not use contextual information, even under conditions
      designed to maximize their use of such cues, but that adult-like processing is
      evident by approximately 8 years of age. These results support and extend
      previous findings by Trueswell and colleagues (Cognition (1999), Vol. 73, pp. 89
      134) and are consistent with a constraint-based learning account of children's
      linguistic development.

PMID- 18070630
TI  - Pathology and the humanities.

PMID- 18070629
TI  - Purification, identification and activity of phomodione, a furandione from an
      endophytic Phoma species.
AB  - Phomodione, [(4aS(*),9bR(*))-2,6-diacetyl-7-hydroxy-4a,9-dimethoxy-8,9b-dimethyl
      4a.9b-dihydrodibenzo[b,d]furan-1,3(2H,4H)-dione], an usnic acid derivative, was
      isolated from culture broth of a Phoma species, discovered as an endophyte on a
      Guinea plant (Saurauia scaberrinae). It was identified using NMR, X-ray
      crystallography, high resolution mass spectrometry, as well as infrared and Raman
      spectroscopy. In addition to phomodione, usnic acid and cercosporamide, known
      compounds with antibiotic activity, were also found in the culture medium.
      Phomodione exhibited a minimum inhibitory concentration of 1.6 microg/mL against
      Staphylococcus aureus using the disk diffusion assay, and was active against a
      representative oomycete, ascomycete and basidiomycete at between three and eight
      micro-grams per mL.

PMID- 18070631
TI  - Adult diffuse nesidioblastosis: genetically or environmentally induced?
AB  - Persistent hyperinsulinemic hypoglycemia in adults is usually caused by solitary
      benign insulinomas. Nesidioblastosis, a term that has been used to designate a
      functional disorder of the beta cells, is a rare cause of persistent
      hyperinsulinemic hypoglycemia in adults, but seems to have increased in
      frequency. The histopathologic criteria for adult nesidioblastosis are similar to
      those used for the diagnosis of the diffuse form of congenital hyperinsulinism in
      infants and include beta-cell hypertrophy, islet hyperplasia, and an increase in
      the beta-cell mass. However, the degree and extent of these features vary much
      more from patient to patient than in newborns. The cause of adult
      nesidioblastosis is not known, but the recently observed association with gastric
      bypass surgery in obese patients suggests that a reactive process possibly
      unmasks or induces a defect in the beta cell, resulting in its hyperfunction.

PMID- 18070632
TI  - Autoimmune lymphoproliferative syndrome in a patient with a new minimal deletion
      in the death domain of the FAS gene.
AB  - We present a case of autoimmune lymphoproliferative syndrome (ALPS) caused by a
      previously undescribed minimal deletion in the death domain of the FAS gene. ALPS
      is an uncommon disease associated with an impaired Fas-mediated apoptosis. The
      patient presented with a history of splenomegaly since 4 months of age,
      associated with cervical lymphadenopathy, which improved with oral corticosteroid
      treatment. Relevant laboratory findings were the presence of anemia,
      thrombocytopenia, and positive direct and indirect Coombs tests. He was not an
      offspring of consanguineous parents. Two cervical lymph node biopsies were
      performed, at 4 years and at 6 years of age. In both lymph nodes, there was
      marked paracortical expansion by lymphocytes in variable stages of immunoblastic
      transformation and a very high cell proliferating index. Some clear cells were
      also present, raising the suspicion of malignant lymphoma. In one of the lymph
      nodes, there was also a focus rich in large histiocytes with round nuclei and
      emperipolesis, consistent with focal Rosai-Dorfman disease. Immunostaining showed
      numerous CD3+ cells, many of which were double-negative (CD4- CD8-) and expressed
      CD57, especially around the follicles. Molecular studies of the lymph node biopsy
      showed a point deletion (4-base pair deletion) in exon 9 of the FAS gene (930del
      TGCT), which results in 3 missense amino acids.

PMID- 18070633
TI  - Bilateral mixed epithelial stromal tumor in an end-stage renal disease patient:
      the first case report.
AB  - Although first intimated in the 1970s, mixed epithelial stromal tumor has been
      recognized as a diagnostic entity for less than 10 years, with an identity that
      has been challenged by overlap between other cystic renal neoplasms, most notably
      with cystic nephroma. We report the first case of a bilateral mixed epithelial
      stromal tumor occurring in a 41-year-old dialysis-dependent woman, notably also
      the first case reported in a patient with end-stage renal disease. The neoplasms
      occurred 5 years apart and were diagnosed as mixed epithelial stromal tumor in
      both instances. We describe the presentation and pertinent radiologic,
      histologic, and immunophenotypic findings of these neoplasms with a review of the
      current debate regarding mixed epithelial stromal tumor and cystic nephroma
      taxonomy.

PMID- 18070635
TI  - Preliminary results of nonconstrained pyrolytic carbon arthroplasty for
      metacarpophalangeal joint arthritis.
AB  - PURPOSE: To review early outcomes of arthritic metacarpophalangeal (MCP) joints
      treated with nonconstrained pyrolytic carbon implants to evaluate efficacy,
      clinical outcomes, and durability. METHODS: One hundred forty-two consecutive
      arthroplasties (61 patients) were retrospectively reviewed. Diagnoses included
      osteoarthritis (OA), traumatic arthritis, and inflammatory arthritis. One hundred
      thirty were primary joint replacements, and 12 were prior-silicone revisions. The
      average patient age was 55 years (range, 21-77 years); 36 patients were women and
      25 were men. Average follow-up period was 17 months (range, 3-42 months), and 43
      patients were followed up for a minimum of 1 year. RESULTS: For OA patients,
      according to the analog pain scale used, pain decreased from 73.0 to 8.5 of 100,
      functionality increased from 20.1 to 86.6 of 100, and appearance improved from
      62.7 to 93.6 of 100. The rheumatoid arthritis (RA) group showed decreased pain
      from 43.1 to 8.9 of 100, functional improvement from 26.7 to 83.3 of 100, and
      increased appearance from 25.2 to 77.1 of 100. At 1 year, satisfaction was
      greater than 90% for both groups. Arc of motion for OA patients improved from 44
      degrees to 58 degrees . Oppositional pinch increased 126%, and grip strength
      improved 40%. Rheumatoid arthritis patients increased their MCP joint motion arc
      from 32 degrees to 45 degrees . Oppositional pinch increased 89%, but grip
      strength decreased. Radiographs at 1 year demonstrated stable prostheses in all
      of the OA joints. The RA group overall demonstrated evidence of axial subsidence
      (10.5% of joints) and periprosthetic erosions (16.4% of joints). In RA joints
      with greater than 1-year follow-up period, 55.0% had axial subsidence, 95.0% had
      an increased radiolucent seam, and 45.0% had periprosthetic erosions. The overall
      implant survivorship is 141 joints to date. The overall minor complication rate
      was 6%, and major complication rate was 9%. CONCLUSIONS: Preliminary results
      suggest that pyrolytic carbon MCP joint arthroplasty provides good pain relief,
      patient satisfaction, and functional improvement in managing OA and select cases
      of RA. Longer follow-up evaluation will help validate these promising early
      results. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 18070636
TI  - Results of revision metacarpophalangeal joint surgery in rheumatoid patients
      following previous silicone arthroplasty.
AB  - PURPOSE: Primary silicone metacarpophalangeal (MCP) joint arthroplasties have
      good results that deteriorate with time. The purpose of this study was to assess
      indications, patient satisfaction, and clinical and radiographic results
      following revision surgery in rheumatoid patients who had previously undergone
      silicone MCP arthroplasty. METHODS: Twenty hands in 18 patients (62 implants) had
      revision silicone MCP arthroplasties between 1986 and 2005 and had a greater than
      1-year follow-up period (mean 5 y). A retrospective chart review was performed to
      collect preoperative and intraoperative data. Patients were then re-examined and
      administered a questionnaire addressing subjective outcome and satisfaction.
      RESULTS: Intraoperatively, 76% of the implants were fractured. Thirteen of 17
      synovial biopsies revealed giant cell foreign body reaction. Preoperatively, the
      average arc of motion was from 16 degrees to 50 degrees , and ulnar drift was 24
      degrees . Postoperatively, the average arc of motion was from 20 degrees to 54
      degrees , and ulnar drift was 13 degrees . X-rays of 14 hands revealed that 15 of
      44 revised implants had fractured. Sixteen patients (18 hands) were available to
      complete questionnaires. Twelve patients (14 hands) were satisfied and 3 were
      dissatisfied. Five of 16 patients would not have the revision again. These
      patients had worse average postoperative ulnar drift (30 degrees vs 9 degrees )
      than the other 11 patients. All patients except one who had preoperative pain had
      at least moderate pain relief, and of the 6 patients who had revision surgery
      because of pain, 5 were satisfied. CONCLUSIONS: Revision silicone arthroplasty
      provides excellent pain relief, and the majority of patients were pleased with
      their results. Objective results, however, were generally poor. Soft tissue
      reconstruction is more difficult to achieve than the primary procedure, as
      evidenced by minimal improvement in ulnar drift, a high rate of implant fracture,
      and no change in arc of motion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 18070637
TI  - Extra-articular steroid injection: early patient response and the incidence of
      flare reaction.
AB  - PURPOSE: To evaluate the timing of improvement after extra-articular steroid
      injection, the incidence of a postinjection pain flare (a delayed postinjection
      transient increase in pain), and the role of the injection acidity in the
      postinjection flare. METHODS: One hundred twenty-five patients with trigger
      finger (88 patients) or de Quervain's tenosynovitis (37 patients) were
      prospectively randomized in this double-blind study to receive either an
      injection of steroid, lidocaine, and bupivacaine alone (standard injection,
      acidic pH) or an injection of steroid, lidocaine, bupivacaine, and bicarbonate
      (balanced injection, neutral pH). All patients completed a visual analog scale
      for pain before and immediately after the injection, daily for 7 days, and then
      again at 6 weeks. A flare reaction was defined as an increase in the visual
      analog scale score by 2 or more points any time after the injection. RESULTS: All
      patients immediately responded to the steroid injection, but pain rebounded to
      preinjection levels by day 1. In both groups the pain then gradually declined
      over the course of 7 days. In the balanced group, 23 of the 68 patients had flare
      reactions. In the standard group, 18 of the 57 patients had flare reactions. The
      difference between groups was not significant. CONCLUSIONS: Patients respond to
      extra-articular steroid injections with gradual improvement over the course of
      the first week. An increase in pain, or flare reaction, in the days following a
      steroid injection was noted in 33% of patients. A pH-balanced injection did not
      significantly decrease the risk of a flare reaction. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic I.

PMID- 18070638
TI  - A comparison of polyglycolic acid versus type 1 collagen bioabsorbable nerve
      conduits in a rat model: an alternative to autografting.
AB  - PURPOSE: Severe nerve injury with segmental loss requires nerve graft or conduit
      repair. We compared 2 synthetic, bioabsorbable nerve conduits with the gold
      standard of autogenous nerve grafting using histopathologic and neurophysiologic
      analyses. METHODS: A 10-mm segment of the sciatic nerve of 45 Sprague-Dawley rats
      was resected, leaving a gap defect. Three experimental groups were used: 15
      coaptations using type I collagen nerve conduits, 15 coaptations using
      polyglycolic acid (PGA) nerve conduits, and 15 coaptations using the excised
      segments as autogenous nerve grafts. The contralateral legs were used as
      unoperated controls. After 15 weeks, nerve regeneration was evaluated by
      measuring isometric muscle contraction force, axonal counting, wet muscle
      weights, and histology. RESULTS: Statistically significant differences in the
      isometric muscle contraction force, axonal counts, and wet muscle weights were
      found between type I collagen conduit and nerve graft compared to the PGA
      conduit. Axonal sprouting was less organized and less dense with the PGA conduits
      when compared to nerve reconstruction with the type I collagen conduits and nerve
      grafts. CONCLUSIONS: Type I collagen conduits and autografts produced comparable
      results, which were significantly better than PGA conduits. The use of type I
      collagen conduit is a reliable alternative to nerve grafting for gaps up to 10 mm
      in length.

PMID- 18070639
TI  - Intraneural lipoma of the posterior interosseous nerve.
AB  - Lipomas arising in the peripheral nerves are rare tumors, with most arising in
      the forearm and wrist, and most have occurred within the median nerve. This
      report describes a case with large lipoma arising in the posterior interosseous
      nerve.

PMID- 18070641
TI  - Segmental neurofibromatosis of the hand and upper extremity: a case report.
AB  - A case of segmental neurofibromatosis of the upper extremity is presented.
      Multiple neurofibromas involving different peripheral nerves limited to a single
      body part or limb is a rare form of neurofibromatosis. The clinical, genetic, and
      histologic findings of segmental neurofibromatosis are described. The criteria
      for segmental neurofibromatosis are reviewed, and the differentiation of
      neurofibromatosis types 1 and 2 and schwannomatosis is also briefly reviewed.

PMID- 18070640
TI  - Release of the transverse carpal ligament alone is associated with elevated
      pressure beneath the distal volar forearm fascia in a cadaver model of carpal
      tunnel syndrome.
AB  - PURPOSE: The purpose of this study is to determine whether release of the distal
      volar forearm fascia (DVFF) is necessary at the time of median nerve
      decompression for carpal tunnel syndrome. METHODS: Five fresh-frozen cadaver
      specimens were mounted vertically with the hand dependent and a 2.27-kg weight
      suspended from the fingers. A pressure sensor wire was used to measure pressures
      starting just distal to the transverse carpal ligament (TCL). The wire was
      withdrawn proximally in 5-mm increments and into the forearm until pressure was
      below 10 mm Hg. An incision in the forearm was extended distally until the
      pressure sensor was found. The distance from this point to the distal volar wrist
      crease was measured. The TCL was released, keeping the DVFF intact, and the
      experiment was repeated. Paired t-tests determined whether there were
      statistically significant differences between measurements before and after TCL
      release. RESULTS: Average peak pressure under the intact TCL was 57.8 +/- 10.1 mm
      Hg. Average peak pressure under the DVFF with the TCL intact was 61.2 +/- 43.6 mm
      Hg. Following release of the TCL, average peak pressure beneath the TCL
      significantly decreased to 14.0 +/- 9.0 mm Hg, whereas average peak pressure at
      the intact DVFF increased to 64.8 +/- 48.7 mm Hg. Average locations where DVFF
      pressure became less than 10 mm Hg with an intact TCL and with released TCL were
      4.30 +/- 1.8 cm and 4.00 +/- 1.8 cm proximal to the distal volar wrist crease,
      respectively. There was no significant difference between DVFF pressures before
      or after TCL release. CONCLUSIONS: In a cadaver model of carpal tunnel syndrome,
      release of the TCL alone is associated with persistent pressures >30 mm Hg in the
      region of the DVFF. Release of the TCL did not significantly change the location
      of the pressure drop-off under the DVFF.

PMID- 18070642
TI  - Flexor tendon grafting using a plantaris tendon with a fragment of attached bone
      for fixation to the distal phalanx: a preliminary cohort study.
AB  - PURPOSE: Secure methods of graft attachment ensure safe early motion after flexor
      tendon grafting. This has been achieved at the proximal graft juncture using
      Pulvertaft's technique. For secure distal attachment, we investigate the results
      of flexor tendon grafting using the plantaris tendon with a fragment of attached
      bone fixed with a screw to the distal phalanx. METHODS: Thirteen digits from 10
      patients with longstanding flexor tendon injuries in zone II had surgical
      reconstruction. A plantaris tendon-bone graft was attached to the distal phalanx
      using a mini-screw. This was followed by immediate active motion. At 3 and 8
      months after surgery, total active motion was calculated as the sum of the
      degrees of active flexion in the proximal and distal interphalangeal joints minus
      the sum of the degrees of extension deficits for each of these joints. The
      results of total active motion were compared to the normal contralateral digit.
      RESULTS: Three months after surgery, the mean rate of recovery, relative to the
      normal contralateral finger, was 74%, whereas 8 months after surgery, this value
      was 70%. This difference was statistically significant. There were no failures or
      poor results (ie, less than 50% recovery). CONCLUSIONS: The tendon-bone plantaris
      graft employed here ensured immediate active motion and early use of the involved
      hand in daily activities. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 18070643
TI  - Flexor tendon injuries in pediatric patients.
AB  - PURPOSE: The purpose of this research was to study the incidence and outcome of
      flexor tendon injuries in pediatric patients. METHODS: A survey of flexor tendon
      repair in children less than 16 years of age was performed in the City of
      Helsinki during 2000-2005. A retrospective clinical outcome study of all
      consecutive 28 patients with 45 involved fingers treated in Children's Hospital
      was also performed at a mean 38 months (range 12-53 months) after surgery. Active
      motion program after multistrand tendon repair was used in 33 fingers, cast
      immobilization in 11 fingers, and elastic bands in 1 finger. Functional and
      cosmetic subjective result was evaluated by a visual analog scale (VAS, 0-100).
      Range of motion (ROM) of metacarpophalangeal (MCP) and interphalangeal (IP)
      joints were measured. Grip strength was recorded. Functional outcome methods of
      Buck-Gramcko, ASSH, Strickland, and distal interphalangeal joint (DIP) ROM
      methods were applied. RESULTS: The calculated annual incidence of finger flexor
      injury per child in Helsinki was 0.036 per 1000. There were no ruptures of the
      multistrand repairs with active motion program, but three 2-strand core sutures
      failed within 1 month of the repair. Mean functional and cosmetic VAS scores (all
      28 patients) were 87 and 84. Mean ROM ratio of the DIP joint in zone 1 and 2
      injuries was 60%, compared to 98% in zone 3 and 5 injuries. Ranges of motion of
      the proximal interphalangeal (PIP) and MCP joints were practically normal in all
      patients. There was a discrepancy among the functional outcome scores, with good
      and excellent results in all 45 fingers (Buck-Gramcko), in 39 fingers (ASSH), in
      36 fingers (original Strickland), and in 32 fingers (DIP ROM). CONCLUSIONS:
      Flexor tendon injuries in children are rare. Both subjective and objective
      outcomes are generally good. Active motion program is an effective technique
      after multistrand flexor tendon repair at all levels in children. Range of motion
      of the DIP joint may be a more effective means of evaluating outcome in pediatric
      flexor tendon injuries. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 18070644
TI  - Pediatric trigger finger from calcific tendonitis.
AB  - In pediatric patients, triggering of digits other than the thumb is uncommon and
      can have unique etiology. We present a juvenile patient whose trigger finger was
      associated with a solid calcified nodule on the flexor digitorum superficialis
      tendon.

PMID- 18070645
TI  - Open reduction and internal fixation of Mason type III radial head fractures with
      and without an associated elbow dislocation.
AB  - PURPOSE: The purpose of this study was to evaluate the treatment of patients with
      Mason type III radial head fracture with and without elbow dislocation by open
      reduction with internal fixation, collateral ligament repair, and early
      mobilization. An additional purpose was to investigate whether there is any
      effect of elbow dislocation on the severity and functional outcome. METHODS:
      Twenty-five patients were treated with open reduction with internal fixation
      using low-profile miniplate and screws for comminuted fracture of the radial
      head. Eighteen fractures were Mason type III, and 7 fractures were Mason type III
      with elbow dislocation. There were 5 women and 20 men with a mean age of 34
      years. The mean follow-up time was 27 months. Patients were reviewed for
      functional ability, physical examination, and radiographic assessment. RESULTS:
      The mean functional index in Mason type III fracture and Mason type III fracture
      with elbow dislocation was 87 for both groups. The mean range of motion at the
      elbow joint was calculated as 5 degrees extension to 136 degrees flexion for
      Mason type III and 7 degrees extension to 133 degrees flexion for Mason type III
      with elbow dislocation. The mean pronation and supination for all patients were
      74 degrees and 67 degrees , respectively. CONCLUSIONS: Selected Mason III radial
      head fractures and fracture dislocations could be stabilized satisfactorily with
      internal fixation. Meticulous surgical technique, combined with rigid internal
      fixation, can allow early motion of the forearm and elbow after fixation of Mason
      type III radial head fractures with and without elbow dislocation and ligamentous
      injury. We believe there is still a role for prosthetic replacement in comminuted
      Mason III radial head fractures that cannot reliably be treated with open
      reduction and internal fixation. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 18070646
TI  - Stability of radial head and neck fractures: a biomechanical study of six
      fixation constructs with consideration of three locking plates.
AB  - PURPOSE: Open reduction and internal fixation of radial neck fractures can lead
      to secondary loss of reduction and nonunion due to insufficient stability.
      Nevertheless, there are only a few biomechanical studies about the stability
      achieved by different osteosynthesis constructs. METHODS: Forty-eight formalin
      fixed, human proximal radii were divided into 6 groups according to their bone
      density (measured by dual-energy x-ray absorptiometry). A 2.7-mm gap osteotomy
      was performed to simulate an unstable radial neck fracture, which was fixed with
      3 nonlocking implants: a 2.4-mm T plate, a 2.4-mm blade plate, and 2.0-mm crossed
      screws, and 3 locking plates: a 2.0-mm LCP T plate, a 2.0-mm 6x2 grid plate, and
      a 2.0-mm radial head plate. Implants were tested under axial (N/mm) and torsional
      (Ncm/ degrees ) loads with a servohydraulic materials testing machine. RESULTS:
      The radial head plate was significantly stiffer than all other implants under
      axial as well as under torsional loads, with values of 36 N/mm and 13 Ncm/
      degrees . The second-stiffest implant was the blade plate, with values of 20 N/mm
      and 6 Ncm/ degrees . The weakest implants were the 2.0-mm LCP, with values of 6
      N/mm and 2 Ncm/ degrees , and the 2.0-mm crossed screws, with values of 18 N/mm
      and 2 Ncm/ degrees . The 2.4-mm T plate, with values of 14 N/mm and 4 Ncm/
      degrees , and the 2.0-mm grid plate, with values of 8 N/mm and 4 Ncm/ degrees
      came to lie in the midfield. CONCLUSIONS: The 2.0-mm angle-stable plates
      depending on their design-allow fixation with comparable or even higher stability
      than the bulky 2.4-mm nonlocking implants and 2.0-mm crossed screws.

PMID- 18070647
TI  - The Wrightington approach to the radial head: biomechanical comparison with the
      posterolateral approach.
AB  - PURPOSE: The Wrightington approach to the radial head involves elevating anconeus
      from the proximal ulna to expose the supinator crest and then osteotomizing the
      bony insertion of the lateral ligament complex to the ulna. This avoids incising
      through the substance of the lateral ligament complex. The purpose of this study
      was to determine if there is any difference in laxity changes between using the
      posterolateral versus the Wrightington approach in performing surgery upon the
      radial head in a cadaveric model. METHODS: Ten cadaveric elbows had a radial head
      fracture created and the medial collateral ligament divided. They then
      sequentially had the posterolateral or Wrightington approach to the radial head,
      fracture fixation, head excision, and replacement. After each step, valgus and
      varus laxity and ulnar rotation were determined with an electromagnetic tracking
      system. RESULTS: After each step, there was a greater increase in valgus and
      varus laxity in the posterolateral group compared with the Wrightington group.
      After surgical exposure, radial head fracture fixation, and radial head excision,
      there was a statistically significant difference in the changes in rotation
      between the posterolateral and Wrightington approaches, with the former resulting
      in an increase in external and the latter an increase in internal rotation.
      CONCLUSIONS: These results suggest that the newly described Wrightington approach
      is biomechanically superior to the posterolateral approach with regard to changes
      in elbow laxity after surgery to the radial head.

PMID- 18070648
TI  - Anterior ulnohumeral compression plate arthrodesis for revision complex elbow
      injury: a case report.
AB  - Elbow arthrodesis can be used for complex elbow injuries that are complicated or
      fail other conventional treatment methods. We present a case report of an
      anterior ulnohumeral compressive plate elbow arthrodesis for a patient with a
      complex elbow injury from a gunshot wound that failed initial open reduction and
      internal fixation and posterior ulnohumeral arthrodesis secondary to numerous
      complications.

PMID- 18070649
TI  - Radical resection of a massive venous malformation of the thumb and immediate
      reconstruction with a microsurgical toe transfer.
AB  - A massive venous malformation involving the entire thumb, first web space, and
      index finger in a young child was treated by radical resection of the venous
      malformation, including amputation of the thumb distal to the mid-metacarpal and
      immediate reconstruction with a microsurgical second toe transfer. Five years
      after surgery, the patient has excellent function of the hand and no evidence of
      recurrence of the malformation. This case is unique in two respects: first, the
      venous malformation was of massive size, and second, the unusual venous
      malformation required total amputation of the thumb and immediate reconstruction
      with a complete toe transfer.

PMID- 18070650
TI  - Anomalous supratendinous course of the fifth extensor compartment artery: a case
      report.
AB  - Vascularized bone grafts have been successfully used in the treatment of carpal
      bone nonunion and avascular necrosis. The 4 + 5 extensor compartmental
      vascularized bone graft based on the fourth extensor compartment artery with
      retrograde blood flow through the fifth extensor compartment artery is the
      pedicle of choice for vascularized bone grafting of the lunate. This case report
      describes an anomalous supratendinous course of the fifth extensor compartment
      artery. The recognition of this anatomic variant is important for the safe
      dissection of the fifth extensor compartment artery.

PMID- 18070651
TI  - The medical Doppler in hand surgery: its scientific basis, applications, and the
      history of its namesake, Christian Johann Doppler.
AB  - The word Doppler is used synonymously in hand surgery for evaluating patency of
      vascular structures; however, the science and history behind the Doppler effect
      are not as well-known. We will present the theories behind the Doppler effect and
      the history of the person who made this discovery.

PMID- 18070652
TI  - The clinical applications of peripheral nerve imaging in the upper extremity.
AB  - Use of different imaging modalities in the diagnosis of peripheral nerve
      pathology has been growing steadily. This review attempts to summarize their use,
      particularly with regard to ultrasound and magnetic resonance imaging, and their
      practical applications in the clinical setting.

PMID- 18070653
TI  - The posttraumatic stiff elbow: a review of the literature.
AB  - Loss of motion is a common complication of elbow trauma. Restoration of joint
      motion in the posttraumatic stiff elbow can be a difficult, time-consuming, and
      costly challenge. In this review of the literature, the biologic response to
      trauma and the possible etiologic events that may lead to fibrosis of the
      capsules and heterotopic ossification will be discussed, as well as nonsurgical
      and surgical management of stiffness and expected outcomes of treatment.

PMID- 18070654
TI  - External fixation of distal radius fractures.
AB  - External fixation has been used for the treatment of distal radius fractures for
      more than 50 years. Although the fixator configurations have undergone
      considerable modification over time, the type of fixator itself is not as
      important as the underlying principles that provide the foundation for external
      fixation. Although volar plate fixation is currently in vogue, the indications
      for external fixation remain largely unchanged. Newer fixator designs have also
      expanded the traditional usage to include nonbridging applications that allow
      early wrist motion. The following discussion focuses on the myriad uses for
      external fixation as well as the shortcomings and potential pitfalls.

PMID- 18070655
TI  - A decision-analysis model to diagnose feigned hand weakness.
AB  - Malingering is a condition in which patients exaggerate incapacity. Feigned hand
      weakness is one form of malingering, and it is often seen after work-related hand
      injuries. Malingering is prevalent in the workers' compensation system, which
      devotes a large proportion of valuable resources to unwarranted claims. Feigned
      hand weakness must be detected early because it is relatively prevalent and
      expensive to society. Clinical evaluation is the first step in detecting feigned
      hand weakness, but it is not very specific. Therefore, every suspected positive
      clinical result must be followed up with a more advanced test that has better
      specificity. Three advanced tests are (1) five-rung grip test, (2) rapid grip
      tests (rapid exchange grip and rapid simultaneous grip), and (3) computerized
      measure of grip. Among these, computerized measure of grip is the most specific;
      therefore, it is the best second-line test.

PMID- 18070656
TI  - Regarding "Oxidation of Silicone Elastomer Finger Joints".

PMID- 18070658
TI  - A randomized clinical trial comparing low-glycemic index versus ADA dietary
      education among individuals with type 2 diabetes.
AB  - OBJECTIVE: We compared the effects of a low glycemic index (GI) diet with the
      American Diabetes Association (ADA) diet on glycosylated hemoglobin (HbA1c) among
      individuals with type 2 diabetes. METHODS: Forty individuals with poorly
      controlled type 2 diabetes were randomized to a low-GI or an ADA diet. The
      intervention, consisting of eight educational sessions (monthly for the first 6
      mo and then at months 8 and 10), focused on a low-GI or an ADA diet. Data on
      demographics, diet, physical activity, psychosocial factors, and diabetes
      medication use were assessed at baseline and 6 and 12 mo. Generalized linear
      mixed models were used to compare the two groups on HbA1c, diabetic medication
      use, blood lipids, weight, diet, and physical activity. RESULTS: Participants
      (53% female, mean age 53.5 y) were predominantly white with a mean body mass
      index of 35.8 kg/m(2). Although both interventions achieved similar reductions in
      mean HbA1c at 6 mo and 12 mo, the low-GI diet group was less likely to add or
      increase dosage of diabetic medications (odds ratio 0.26, P = 0.01). Improvements
      in high-density lipoprotein cholesterol, triacylglycerols, and weight loss were
      similar between groups. CONCLUSION: Compared with the ADA diet, the low-GI diet
      achieved equivalent control of HbA1c using less diabetic medication. Despite its
      limited size, this trial suggests that a low-GI diet is a viable alternative to
      the ADA diet. Findings should be evaluated in a larger randomized controlled
      trial.

PMID- 18070659
TI  - Effects of dietary fish oil on lipid peroxidation and serum triacylglycerol
      levels in psychologically stressed mice.
AB  - OBJECTIVE: The intake of omega-3 polyunsaturated fatty acids and psychological
      stress can each induce tissue lipid peroxidation. In our present study, we
      investigated their combined effects on the oxidative status of mouse tissues.
      METHODS: Mice were group-housed (four mice/cage) and fed a diet containing fish
      oil (as a source of omega-3 polyunsaturated fatty acids), soybean oil, or olive
      oil for 3 wk. These animals were then 1) housed under the same conditions (four
      per cage, control group) or 2) individually housed to generate psychological
      stress conditions (isolation stress). After 2 wk of isolation stress, the levels
      of thiobarbituric acid-reactive substances (an index of lipid peroxidation) and
      antioxidants in the liver and kidney and the serum levels of triacylglycerol were
      measured. RESULTS: Fish oil-fed mice showed increased levels of thiobarbituric
      acid-reactive substances in their livers and kidneys compared with soybean oil-
      or olive oil-fed mice. These increases in thiobarbituric acid-reactive substance
      levels in the fish oil-fed mice were less profound under isolation stress
      conditions when compared with the group-housed animals on the same diet. In the
      fish oil-fed mice, isolation stress led to an increase in liver vitamin E levels
      when compared with their group-housed counterparts. The fish oil-fed mice
      exhibited lower serum triacylglycerol levels compared with the soybean oil- or
      olive oil-fed mice, and this decrease was more profound under conditions of
      isolation stress when compared with group-housing conditions. CONCLUSION: Dietary
      fish oil combined with isolation stress results in lower levels of lipid
      peroxidation in the liver and kidney compared with dietary fish oil alone.

PMID- 18070660
TI  - Nutritional recovery with a soybean flour diet improves the insulin response to a
      glucose load without modifying glucose homeostasis.
AB  - OBJECTIVE: We investigated the effect of nutritional recovery with a soybean
      flour diet on glucose tolerance, insulin response to a glucose load, and the
      action of insulin in adult rats exposed to a protein deficiency during
      intrauterine life and lactation. METHODS: Male Wistar rats from dams fed a normal
      or low-protein diet during pregnancy and lactation were maintained after weaning
      by feeding them normal-protein isoenergetic diets containing soybean flour or
      casein and low-protein casein diet. RESULTS: Rats fed a soybean flour diet had a
      lower final body weight, epididymal fat pad, carcass fat content, and liver
      glycogen level. The serum glucose concentrations in the basal and fed states and
      the area under the glucose curves during the glucose tolerance test were not
      significantly different among the four groups. Their serum insulin levels during
      fasting were observed to be similar to those fed a casein diet. These rats also
      had a higher serum insulin levels in a fed state and total area under the insulin
      curves in response to a glucose load, but a lower ratio of area under the
      glucose/insulin curves during the glucose tolerance test than those fed a casein
      diet. CONCLUSION: These results indicate that nutritional recovery with a soybean
      flour diet improved the insulin response to a glucose load and decreased the
      sensitivity to insulin, at least in hepatic tissue.

PMID- 18070661
TI  - Glucose transport in fibroblasts is unaffected by polyamines.
AB  - OBJECTIVE: Wound healing is characterized by a net increase in glucose
      utilization in wound tissues. The mediators involved in this process remain
      largely unknown. Because polyamines are known to stimulate d-glucose uptake in
      brush-border membrane vesicles, we investigated whether or not they stimulated
      sugar uptake in confluent cultured fibroblasts. METHODS: Cells (at a quiescent or
      growing state) were incubated for 1 h with various concentrations (0.5-4 mM) of
      putrescine, spermine, or spermidine or for a range of times (30 min to 3 h) with
      2 mM of these same polyamines. Cultures were then incubated for 5 min at +37
      degrees C with 2-deoxy-d-[1-(3)H] glucose. RESULTS: Polyamines were found to have
      no action on sugar uptake in any of the experimental configurations. CONCLUSION:
      These data suggest that polyamines have no effect in cell types in which glucose
      uptake is mediated by a passive facilitated diffusion process (energy
      independent). This contrasts with results obtained with cells in which sugar
      uptake is dependent on adenosine triphosphate. Even if this model does not
      reflect the complexity of wound healing, these negative results are nevertheless
      important because they suggest that the arginine- and ornithine-mediated effects
      on wound healing are not related to a polyamine-mediated increase in glucose
      transport in fibroblasts.

PMID- 18070662
TI  - An insight into the sialome of the soft tick, Ornithodorus parkeri.
AB  - While hard ticks (Ixodidae) take several days to feed on their hosts, soft ticks
      (Argasidae) feed faster, usually taking less than 1h per meal. Saliva assists in
      the feeding process by providing a cocktail of anti-hemostatic, anti-inflammatory
      and immunomodullatory compounds. Saliva of hard ticks has been shown to contain
      several families of genes each having multiple members, while those of soft ticks
      are relatively unexplored. Analysis of the salivary transcriptome of the soft
      tick Ornithodorus parkeri, the vector of the relapsing fever agent Borrelia
      parkeri, indicates that gene duplication events have led to a large expansion of
      the lipocalin family, as well as of several genes containing Kunitz domains
      indicative of serine protease inhibitors, and several other gene families also
      found in hard ticks. Novel protein families with sequence homology to insulin
      growth factor-binding protein (prostacyclin-stimulating factor), adrenomedulin,
      serum amyloid A protein precursor and similar to HIV envelope protein were also
      characterized for the first time in the salivary gland of a blood-sucking
      arthropod. The sialotranscriptome of O. parkeri confirms that gene duplication
      events are an important driving force in the creation of salivary cocktails of
      blood-feeding arthropods, as was observed with hard ticks and mosquitoes. Most of
      the genes coding for expanded families are homologous to those found in hard
      ticks, indicating a strong common evolutionary path between the two families. As
      happens to all genera of blood-sucking arthropods, several new proteins were also
      found, indicating the process of adaptation to blood feeding still continues to
      recent times.

PMID- 18070663
TI  - Characterization of anti-hemostatic factors in the argasid, Argas monolakensis:
      implications for the evolution of blood-feeding in the soft tick family.
AB  - To date, the only anti-hemostatic factors characterized for softs ticks are for
      Ornithodoros moubata and Ornithodoros savignyi, ticks that feeds mainly on
      mammals. This includes thrombin (ornithodorin and savignin), fXa (TAP and fXaI)
      and platelet aggregation (disagegin and savignygrin) inhibitors that belong to
      the BPTI-Kunitz protein family. This raises the question on how well anti
      hemostatic factors will be conserved in other soft tick genera that feeds on
      other vertebrates such as birds. We characterized the anti-hemostatic factors
      from Argas monolakensis, a soft tick that feeds mainly on Californian gulls. The
      main anti-clotting factor (monobin) is an ortholog of ornithodorin and savignin
      and shows similar slow tight-binding kinetics. The main anti-platelet activities
      are apyrase and fibrinogen receptor antagonists (monogrins). The monogrins are
      orthologs of disagregin and savignygrin and like savignygrin presents the RGD
      integrin-recognition motif on the BPTI substrate-binding presenting loop. This
      implies that the anti-hemostatic factors evolved in the ancestral soft tick
      lineage and has been maintained in soft tick species from two distinct genera
      with different host preferences. The Argas derived anti-hemostatic factors bind
      to mammalian targets with affinities similar to that observed for their orthologs
      in the Ornithodoros genus. This cross-reactivity could have facilitated the
      switching of soft ticks from avian to mammalian hosts and can explain in part the
      ability of Argas ticks, to feed on humans, thereby remaining a possible health
      risk.

PMID- 18070665
TI  - Evidence that amino-acid residues are responsible for substrate synergism of
      locust arginine kinase.
AB  - A series of mutants were constructed to investigate the amino-acid residues
      responsible for the synergism in substrate binding of arginine kinase (AK). AK
      contains a pair of highly conserved amino acids (Y75 and P272) that form a
      hydrogen bond. In the locust (Locusta migratoria manilensis) AK, mutants in two
      highly conserved sites can cause pronounced loss of activity, conformational
      changes and distinct substrate synergism alteration. The Y75F and Y75D mutants
      showed strong synergism (Kd/Km=6.2-13.4), while in single mutants, P272G and
      P272R, and a double mutant, Y75F/P272G, the synergism was almost completely lost
      (Kd/Km=1.1-1.4). Another double mutant, Y75D/P272R, had characteristics similar
      to those of the wild-type enzyme. All these results suggest that the amino-acid
      residues 75 and 272 play an important role in regulating the synergism in
      substrate binding of AK. Fluorescence spectra showed that all mutants except
      Y75D/P272R displayed a red shift to different degrees. All the results provided
      direct evidence that there is a subtle relationship between the synergism in
      substrate binding and the conformational change.

PMID- 18070664
TI  - Comparative sialomics between hard and soft ticks: implications for the evolution
      of blood-feeding behavior.
AB  - Ticks evolved various mechanisms to modulate their host's hemostatic and immune
      defenses. Differences in the anti-hemostatic repertoires suggest that hard and
      soft ticks evolved anti-hemostatic mechanisms independently, but raise questions
      on the conservation of salivary gland proteins in the ancestral tick lineage. To
      address this issue, the sialome (salivary gland secretory proteome) from the soft
      tick, Argas monolakensis, was determined by proteomic analysis and cDNA library
      construction of salivary glands from fed and unfed adult female ticks. The
      sialome is composed of approximately 130 secretory proteins of which the most
      abundant protein folds are the lipocalin, BTSP, BPTI and metalloprotease families
      which also comprise the most abundant proteins found in the salivary glands.
      Comparative analysis indicates that the major protein families are conserved in
      hard and soft ticks. Phylogenetic analysis shows, however, that most gene
      duplications are lineage specific, indicating that the protein families analyzed
      possibly evolved most of their functions after divergence of the two major tick
      families. In conclusion, the ancestral tick may have possessed a simple (few
      members for each family), but diverse (many different protein families) salivary
      gland protein domain repertoire.

PMID- 18070667
TI  - Implication of HMGR in homeostasis of sequestered and de novo produced precursors
      of the iridoid biosynthesis in leaf beetle larvae.
AB  - Insects employ iridoids to deter predatory attacks. Larvae of some Chrysomelina
      species are capable to produce those cyclopentanoid monoterpenes de novo. The
      iridoid biosynthesis proceeds via the mevalonate pathway to geranyl diphospate
      (GDP) subsequently converted into 8-hydroxygeraniol-8-O-beta-D-glucoside followed
      by the transformation into the defensive compounds. We tested whether the
      glucoside, its aglycon or geraniol has an impact on the activity of 3-hydroxy-3
      methylglutaryl-CoA reductase (HMGR), the key regulatory enzyme of the mevalonate
      pathway and also the iridoid biosynthesis. To address the inhibition site of the
      enzyme, initially a complete cDNA encoding full length HMGR was cloned from
      Phaedon cochleariae. Its catalytic portion was then heterologously expressed in
      Escherichia coli. Purification and characterization of the recombinant protein
      revealed attenuated activity in enzyme assays by 8-hydroxygeraniol whereas no
      effect has been observed by addition of the glucoside or geraniol. Thus, the
      catalytic domain is the target for the inhibitor. Homology modeling of the
      catalytic domain and docking experiments demonstrated binding of 8
      hydroxygeraniol to the active site and indicated a competitive inhibition
      mechanism. Iridoid producing larvae are potentially able to sequester
      glucosidically bound 8-hydroxygeraniol whose cleavage of the sugar moiety results
      in 8-hydroxygeraniol. Therefore, HMGR may represent a regulator in maintenance of
      homeostasis between de novo produced and sequestered intermediates of iridoid
      metabolism. Furthermore, we demonstrated that HMGR activity is not only
      diminished in iridoid producers but most likely prevalent within the Chrysomelina
      subtribe and also within the insecta.

PMID- 18070666
TI  - Modifications in the N-terminus of an insect cytochrome P450 enhance production
      of catalytically active protein in baculovirus-Sf9 cell expression systems.
AB  - Although baculovirus vectors are powerful tools for the heterologous expression
      of proteins in insect cell cultures, some insect and plant microsomal P450
      proteins are not effectively expressed in this system. Hypothesizing that their
      expression failures might result from collisions between their N-terminal
      sequences and adjacent cytosolic sequences, we compared and mutated the N
      terminus of Papilio multicaudatus CYP6B33, which is inappropriately folded in Sf9
      cells, to sequences present in its Papilio polyxenes CYP6B1 counterpart, which is
      efficiently expressed and appropriately folded. Molecular modeling of the three
      differences in the linker separating the signal anchor domain (SAD) and the
      cytosolic domain identified Val32 in CYP6B33 as a residue potentially important
      for folding and/or positioning of the cytosolic domain. Mutation of Val32 to
      Ala32 in the CYP6B33 linker (CYP6B33 V32A mutant) or replacement of the CYP6B33
      SAD with that of CYP6B1 (CYP6B1 1-20/CYP6B33 21-500 mutant) allowed for
      significant P450 expression, indicating that complex interactions involving both
      the signal anchor and membrane linker affect folding and activity of P450s in
      this heterologous expression system.

PMID- 18070668
TI  - Expression of Manduca sexta serine proteinase homolog precursors in insect cells
      and their proteolytic activation.
AB  - Phenoloxidase (PO)-catalyzed reactions are crucial to the survival of insects
      after a pathogen or parasite infection. In Manduca sexta, active PO is generated
      from its precursor by a prophenoloxidase activating proteinase (PAP) in the
      presence of non-catalytic serine proteinase homologs (SPHs). The PAP and SPHs,
      located at the ends of a branched proteinase cascade, also require limited
      proteolysis to become functional. While the processing enzyme of M. sexta proPAP
      2 and proPAP-3 is known, we are now investigating the proteolytic activation of
      proSPH-1 and proSPH-2. Here, we report the development of a series of Bac-to-Bac
      plasmid vectors for co-expression, secretion, and affinity purification of proSPH
      1 and proSPH-2 from insect cells infected by one baculovirus. The purified
      proteins were characterized and used as substrates in a search for their
      activating enzymes in plasma of the larvae injected with microorganisms.
      Proteolytic processing occurred after the proSPHs had been incubated with
      hydroxyapatite or gel filtration column fractions. The cleaved proteins were
      active as a cofactor for proPO activation by PAP, and coexistence of SPH-1 and
      SPH-2 is essential for manifesting the auxiliary effect.

PMID- 18070669
TI  - Eicosanoids mediate prophenoloxidase release from oenocytoids in the beet
      armyworm Spodoptera exigua.
AB  - Phenoloxidase (PO) plays a critical role in insect immune reactions especially to
      form melanotic encapsulation and phagocytosis by hemocytes. PO is an active form
      of prophenoloxidase (PPO) after proteolytic cleavage by serine proteinase(s). It
      has been suggested that eicosanoids are implicated in PPO activation in the beet
      armyworm, Spodoptera exigua. However, it is not clear how eicosanoids mediate the
      reaction cascade of PPO activation. This study analyzed the PPO activation
      mediated by eicosanoids at both transcriptional and post-transcriptional levels.
      A cDNA encoding PPO (SePPO) was cloned from the hemocytes of S. exigua and its
      putative amino acid sequence shared homology with PPO-2 of other lepidopteran
      insects. Its expression was specific only to hemocytes and inducible in response
      to bacterial challenge. Eicosanoid biosynthesis inhibitors did not influence the
      gene expression of SePPO. Most SePPO proteins were located in a specific hemocyte
      type, oenocytoids, which were subjected to cell rupture to release the cellular
      contents in response to bacterial challenge. There was a significant negative
      correlation between PO activity and intact oenocytoid density. Interestingly,
      this cell rupture to release SePPO from oenocytoids was significantly inhibited
      in the larvae infected with the phospholipase A2-inhibiting bacterium,
      Xenorhabdus nematophila, which was resumed on addition of eicosanoid biosynthesis
      precursor, arachidonic acid. Furthermore, oenocytoids exposed to eicosanoid
      biosynthesis inhibitors such as dexamethasone and bromophenacyl bromide showed
      significant reduction in cell rupture. Prostaglandins, not lipoxygenase products
      appeared to be implicated in the cell rupture. These results indicate that
      eicosanoids mediate SePPO activation only at the post-transcriptional level by
      inducing release of PPO from oenocytoids through cell rupture.

PMID- 18070670
TI  - Genomic analysis of detoxification genes in the mosquito Aedes aegypti.
AB  - Annotation of the recently determined genome sequence of the major dengue vector,
      Aedes aegypti, reveals an abundance of detoxification genes. Here, we report the
      presence of 235 members of the cytochrome P450, glutathione transferase and
      carboxy/cholinesterase families in Ae. aegypti. This gene count represents an
      increase of 58% and 36% compared with the fruitfly, Drosophila melanogaster, and
      the malaria mosquito, Anopheles gambiae, respectively. The expansion is not
      uniform within the gene families. Secure orthologs can be found across the insect
      species for enzymes that have presumed or proven biosynthetic or housekeeping
      roles. In contrast, subsets of these gene families that are associated with
      general xenobiotic detoxification, in particular the CYP6, CYP9 and alpha
      esterase families, have expanded in Ae. aegypti. In order to identify
      detoxification genes associated with resistance to insecticides we constructed an
      array containing unique oligonucleotide probes for these genes and compared their
      expression level in insecticide resistant and susceptible strains. Several
      candidate genes were identified with the majority belonging to two gene families,
      the CYP9 P450s and the Epsilon GSTs. This 'Ae. aegypti Detox Chip' will
      facilitate the implementation of insecticide resistance management strategies for
      arboviral control programmes.

PMID- 18070672
TI  - Neurobiological mechanisms of developmental epilepsy: translating experimental
      findings into clinical application.
AB  - Although seizures are very common during early brain development, consequences of
      seizures during this age period are less severe than in the mature brain. Reasons
      for this discrepancy relate to both the sequential development of neural elements
      (ion channels, neurotransmitters, synapses, and circuits) and the effects of
      seizures on these ongoing processes at different ages. In this review, I
      critically discuss 2 recent experimental trends in developmental neurobiology
      that impact seizures and their consequences. First, the paradoxic excitatory
      effects of gamma-aminobutyric acid early in life are related to seizure
      susceptibility in this developmental period. Second, the plasticity of immature
      neuronal circuits and the effects of seizures on subsequent cognition and
      behavior as a function of age are considered. These topics are relevant to the
      pediatric neurologist when evaluating and treating a young child with seizures.

PMID- 18070674
TI  - Psychiatric and psychosocial consequences of pediatric epilepsy.
AB  - Psychiatric and psychosocial complications with pediatric epilepsy are more
      common than with other chronic medical illnesses. Epilepsy is a disorder of
      hyperexcitable neurons and may have direct neurophysiologic effects leading to
      psychiatric comorbidity. Epilepsy also requires significant lifestyle adjustment,
      and the psychosocial impact on children and their families may be severe. The
      scientific literature is underrepresented in terms of diagnosis and management of
      psychiatric and psychosocial comorbidity associated with pediatric epilepsy.
      However, recent scientific efforts have assisted in highlighting the impact of
      these comorbidities and in bringing them to greater clinical attention. This
      review incorporates the available evidence with an aim to describe effective
      strategies for diagnosis and management.

PMID- 18070675
TI  - Hormonal consequences of epilepsy.
AB  - Epilepsy is a common disorder in childhood. The effects of recurrent seizures and
      the use of antiepileptic drugs (AEDs) during childhood and adolescence on
      reproductive endocrine health are poorly defined. We review effects of hormones
      on epilepsy and vice versa along with the effects of treatment (AEDs) on hormones
      in children.

PMID- 18070676
TI  - Bone consequences of epilepsy and antiepileptic medications.
AB  - Childhood and adolescence are critical periods of skeletal mineralization. Peak
      bone mineral density achieved by the end of adolescence determines the risk for
      later pathological fractures and osteoporosis. Chronic disease and medication
      often adversely affect bone health. Epilepsy is one of the most common
      neurological conditions occurring in persons under the age of 21. Epilepsy may
      affect bone in a number of ways. Restrictions of physical activity imposed by
      seizures, cerebral palsy or other coexisting comorbidities adversely affect bone
      health. It has been observed that treatment with phenytoin and phenobarbital can
      be associated with rickets. More recently, established agents such as
      carbamazepine and valproate have been shown to be associated with decreased bone
      mineral density. The literature related to bone health in pediatric epilepsy is
      reviewed.

PMID- 18070673
TI  - Cognitive and magnetic resonance volumetric abnormalities in new-onset pediatric
      epilepsy.
AB  - This paper addresses the issue of cognitive morbidity and abnormalities in
      quantitative MR volumetric in children with new and recent onset idiopathic
      epilepsy. The available literature suggests that mild diffuse cognitive problems
      are evident in children with new onset epilepsy in the context of intact whole
      brain and lobar volumetrics. Subsets of children can be identified with salient
      academic and volumetric abnormalities. These findings represent the baseline upon
      which any subsequent effects of chronic epilepsy may accrue.

PMID- 18070677
TI  - Complications and consequences of epilepsy surgery, ketogenic diet, and vagus
      nerve stimulation.
AB  - Children with medically intractable epilepsy may be candidates for
      nonpharmacologic therapies such as resective and disconnection epilepsy surgery,
      the ketogenic diet and its variants, and vagus nerve stimulation. Each of these
      therapies offers unique advantages and disadvantages, and careful consideration
      of the risk-benefit analysis must be tailored to each child. The hopeful outcome
      from each of these therapies is seizure freedom or at least a very significant
      improvement in seizure control, with few or no adverse effects. However,
      unfortunate adverse consequences can and do occur. These may be serious and
      irreversible or more commonly mild and transient. An appreciation of these
      complications and consequences is necessary for the comprehensive management of
      these complex patients.

PMID- 18070678
TI  - Inpatient dermatology.

PMID- 18070680
TI  - Approach to the acute, generalized, blistering patient.
AB  - This article discusses the approach to the acute, generalized, blistering patient
      from the perspective of the dermatologic consultant. Initially, a case is
      presented, followed by a discussion of the relevant evaluation, differential
      diagnosis, and treatment options.

PMID- 18070679
TI  - Fever and erythema in the emergency room.
AB  - The emergency department presents difficult cases for the consulting
      dermatologist. One of the most challenging is the patient who presents with fever
      and an erythematous rash. The differential diagnosis of the erythrodermic patient
      in the emergency room can include drug eruptions (DRESS syndrome), Staphylococcal
      scalded skin syndrome, toxic shock syndrome, Kawasaki disease and Kawasaki
      disease-like Syndrome, and recalcitrant erythematous desquamating disorder.
      Evaluating these patients can be frustrating and requires patience and
      thoroughness to arrive at the correct diagnosis.

PMID- 18070681
TI  - Approach to the patient with a suspected drug eruption.
AB  - Diagnosis and management of adverse drug reactions constitutes a significant
      portion of U.S. health care costs. The clinical presentation of these reactions
      varies from self-limited, morbilliform drug eruptions to more severe, systemic
      reactions, such as drug hypersensitivity syndromes, Stevens-Johnson syndrome, and
      toxic epidermal necrolysis, which are associated with significant mortality. The
      role of the consulting dermatologist is to expeditiously and effectively
      recognize and classify these drug reactions on the basis of patient histories and
      awareness of the dermatologic literature as it pertains to the rates of and risk
      factors for adverse cutaneous events associated with use of numerous medications.
      This combined with a systematic approach to the workup of a patient with a
      suspected drug eruption allows for prompt recognition, classification and
      treatment of these unforeseen events.

PMID- 18070682
TI  - Approach to the morbilliform eruption in the hematopoietic transplant patient.
AB  - Morbilliform eruptions occur frequently in the hematopoietic transplant
      population. The differential diagnosis includes drug reaction, viral exanthem,
      and cutaneous graft versus host disease. Using a typical patient case, we discuss
      the diagnostic approach to this clinical problem.

PMID- 18070683
TI  - The role of the hospital dermatologist in the diagnosis and treatment of
      calciphylaxis and nephrogenic systemic fibrosis.
AB  - Calciphylaxis and nephrogenic systemic fibrosis are rapidly progressive diseases
      associated with renal impairment with high rates of mortality and morbidity. In
      this review, we highlight the role of the dermatologist in the multispecialty
      team approach to the diagnosis, treatment, and management of these patients. We
      present sample cases from our hospital practice to emphasize the importance of
      diagnosis, clinicopathologic correlation, rapid intervention, and treatment of
      these challenging skin disorders.

PMID- 18070684
TI  - Approach to the patient with presumed cellulitis.
AB  - Dermatologists frequently are consulted in the evaluation and management of the
      patient with cellulitic-appearing skin. For routine cellulitis, the clinical
      presentation and patient symptoms are usually sufficient for an accurate
      diagnosis. However, when the clinical presentation is somewhat atypical, or if
      the patient fails to respond to appropriate therapy for cellulitis because of
      routine bacterial pathogens, the differential diagnosis should be rapidly
      expanded. We discuss the approach to the patient with presumed cellulitis, with
      an emphasis on the differential diagnosis of cellulitis in both the
      immunocompetent and immunucompromised patient.

PMID- 18070685
TI  - A four-year-old boy with fever, rash, and arthritis.
AB  - The triad of fever, rash, and arthritis in a hospitalized child suggests an
      inflammatory, infectious, or postinfectious process in most cases; however,
      malignancy must be considered. The most common causes in this age group are
      inflammatory conditions, including Kawasaki disease, Henoch-Schonlein Purpura,
      serum sickness-like reaction, and juvenile idiopathic arthritis. Other rarer
      inflammatory processes can present with this triad of symptoms such as Cryopyrin
      related diseases (autoinflammatory disorders), urticarial vasculitis, and
      systemic lupus erythematosus. We will discuss the differential diagnosis and
      inpatient management of fever, rash, and arthritis in a young child, focusing on
      inflammatory conditions. The important features which can help distinguish these
      conditions include the nature of the rash, associated signs or symptoms, time
      course of the eruption, and characteristic laboratory and/or histologic findings.

PMID- 18070687
TI  - Image-guided percutaneous needle biopsy in cancer diagnosis and staging.
AB  - Image-guided percutaneous biopsy is a well-established and safe technique and
      plays a crucial role in management of cancer patients. Improvements in needle
      designs, development of new biopsy techniques, and continual advances in image
      guidance technology have improved the safety and efficacy of the procedure.
      Lesions previously considered relatively inaccessible can now be safely biopsied.
      In this article, we review the various needle types, biopsy techniques, methods
      of safely assessing difficult-to-reach lesions, the advantages and disadvantages
      of various imaging modalities, and specific biopsy techniques applicable to
      different regions of the body.

PMID- 18070688
TI  - Thermal ablation of lung tumors.
AB  - Thermal ablation can be applied to treat any thoracic malignancy: primary lung
      cancers, recurrent primary lung cancers, metastatic disease, chest wall masses,
      and painful, bony metastases. Since the first reported use of thermal ablation
      for lung cancer in 2000 there has been an explosive use of the procedure, and by
      2010 the number of procedures to treat thoracic malignancy is expected to exceed
      150,000 per year. Presently, thermal ablation is best used for patients with
      early-stage lung cancers in patients who are not surgical candidates, patients
      with small and favorably located pulmonary metastases, and patients in whom
      palliation of tumor-related symptoms is the goal. Radiofrequency ablation,
      microwave ablation, and cryoablation are novel treatment modalities for lung
      cancer and can safely accomplish tumor destruction and even complete eradication
      of tumor in patients who are not candidates for surgical resection. In this
      article, we discuss technical considerations for each modality and the
      periprocedure and postprocedure management of patients with this disease.

PMID- 18070689
TI  - Transpulmonary chemoembolization: a novel approach for the treatment of
      unresectable lung tumors.
AB  - This article describes the technique of transpulmonary chemoembolization for the
      palliative treatment of unresectable lung tumors. Early utilization of this
      method has resulted in reduction in tumor volume and alleviation of patient
      symptoms. After superselective catheterization, cytotoxic agents are
      administered, and the pulmonary arterial supply of the tumor is occluded by
      injection of microspheres and ethiodized oil. Emerging data suggest that this
      approach is well tolerated.

PMID- 18070690
TI  - Image-guided palliation of painful metastases using percutaneous ablation.
AB  - Painful skeletal metastases are a common problem in cancer patients. Although
      external beam radiation therapy is the current standard of care for cancer
      patients who present with localized bone pain, 20 to 30% of patients treated with
      this modality do not experience pain relief and few further options exist for
      these patients. For many patients with painful metastatic skeletal disease,
      analgesics remain the only alternative treatment option. Recently, image-guided
      percutaneous methods of tumor destruction have proven effective for treatment of
      this difficult problem. Patient selection, treatment methods, and results of
      treatment are described for the use of percutaneous radiofrequency ablation and
      cryoablation for patients with painful metastatic disease.

PMID- 18070691
TI  - Radiofrequency ablation of renal tumors.
AB  - Radiofrequency ablation (RFA) of renal tumors is a promising technique that plays
      a unique and increasingly important role in urologic oncology practices. RFA is
      appealing as a minimally invasive therapy that may be performed on an outpatient
      basis. It enables treatment of an area 3 to 5 cm in diameter, with relatively low
      morbidity and mortality rates. Most interventional radiologists (IRs) are
      familiar with RFA of liver tumors, and several principles and techniques used in
      the liver may be extrapolated for use in the kidney. However, it is crucial to
      bear in mind that local tumor ablation in the kidney presents unique challenges,
      secondary to the kidney's unique anatomic and physiologic features. Clinical and
      technical considerations, risks, and complications pertaining to RFA of renal
      tumors are reviewed here, including approaches commonly used in our practice.

PMID- 18070692
TI  - Image-guided percutaneous cryoablation of renal tumors.
AB  - With the advent of new diagnostic modalities and improvement in techniques, more
      renal tumors are diagnosed at earlier stages. Partial nephrectomy for small renal
      tumors has been shown to be effective for treatment and for preservation of renal
      function; however, this approach also has morbidity and mortality risks. It has
      been more than 30 years since operative cryoablation was first used in urology,
      and the tissue-destructive properties of cryoablation are well established.
      Cryoablation used for tumor destruction has the potential for maximum
      preservation of renal parenchyma. With the advent of smaller cryoprobes, the
      possibility of performing percutaneous image-guided cryoablation has become a
      reality. The technique appears safe. Its efficacy can only be assumed based on
      the literature of operative cryoablation; however, it affords a possible approach
      for patients who cannot undergo surgery.

PMID- 18070693
TI  - Percutaneous image-guided prostate cancer treatment: cryoablation as a successful
      example.
AB  - Prostate cancer is diagnosed in more than 200,000 men a year in the United States
      and an equal number in Europe. Approximately 40,000 US men per year die of the
      disease, second only to lung cancer as a cause of cancer mortality in men.
      Despite the large shadow it casts, the treatment of prostate cancer has in large
      part been ignored by the mainstream of interventional radiology. With the rapid
      growth of interventional oncology and the relative short supply of urologists
      available, interventional radiologists are now in a position to take a major role
      in treating prostate cancer. Prostate cancer is unique in that its prevalence is
      so high (60% of men at the age of 60 have prostate cancer in their gland) it is
      almost a "normal" occurrence. This has caused great controversy in the field,
      however, since it demands answers to the question of which patients really need
      treatment for this disease. Another confounding problem is that the treatments
      until now have been particularly morbid, leaving many men both impotent and
      incontinent. For this reason, a unique situation occurs where many men are now
      being counseled to "observe" their cancer. Interventional image-guided procedures
      have a potentially paradigm-changing role to play in the treatment of prostate
      cancer by markedly reducing the morbidity traditionally associated with
      management of this disease. This article reviews the current role of image-guided
      cryoablation of prostate cancer and the basic principles that will guide
      minimally invasive treatments for this disease in the future.

PMID- 18070694
TI  - Interventional MRI for oncologic applications.
AB  - Interventional radiology plays an important role in the diagnosis and treatment
      of many oncologic disorders. Magnetic resonance imaging (MRI) has excellent soft
      tissue contrast capabilities and allows visualization of anatomical details of
      many organs that is not possible with other imaging modalities. MRI also is
      multiplanar, has the ability to display tissue temperature changes, and uses no
      ionizing radiation. With an open configuration MRI system, the radiologist may
      stand alongside the patient and view images, all while performing an
      interventional procedure. In this article, we explain the rationale for using MRI
      to guide interventions, focus on technical aspects of biopsy, cryoablation,
      focused ultrasound, and brachytherapy, and provide a primer for the
      interventional radiologist wishing to use MRI to guide oncologic interventions.

PMID- 18070696
TI  - The multidisciplinary management of gastrointestinal cancer. Epidemiology of
      oesophagogastric cancer.
AB  - Oesophagogastric cancer occurs in the oesophagus, the oesophagogastric region and
      the stomach, including the proximal and distal stomach. In 2005, the worldwide
      burden of oesophagogastric cancer was estimated to be 1,500,000 new cases
      (500,000 oesophagus and 1,000,000 stomach). Squamous cell cancer is linked with
      alcohol and tobacco consumption in Western countries. Its incidence is much
      higher in regions of Asia with a low-socio-economic status, nutritional
      deficiencies, poor oral status, carcinogens absorbed with smoked meat, fat-cooked
      foodstuffs, vegetables containing toxic alkaloids or mycotoxins, and water
      containing nitrites, nitrates and nitrosamines. Adenocarcinoma develops in the
      columnar lined oesophagus. Its incidence is still low but there is an increasing
      trend. The incidence of stomach cancer is decreasing worldwide, but is still high
      in Japan. Causal factors include Helicobacter pylori infection with atrophic
      gastritis and a diet poor in fruit and vegetables. Preneoplastic conditions of
      the oesophagogastric mucosa include erosive oesophagitis in alcoholics, columnar
      lined oesophagus as a complication of gastro-oesophageal reflux disease, and
      atrophic gastritis following H. pylori infection.

PMID- 18070697
TI  - The multidisciplinary management of gastrointestinal cancer. Multimodal treatment
      of oesophageal cancer.
AB  - Treatment of oesophageal cancer requires a multidisciplinary approach. Single
      modality treatment, especially surgical excision, is only indicated in small
      tumours or in patients unable to support multimodal treatment. In Stage I-II
      adenocarcinoma, multimodal treatment using neoadjuvant therapy is indicated in
      the absence of contra-indications. However, this statement is not universally
      accepted. The choice between radio-chemotherapy and chemotherapy depends on
      patients' characteristics and the preferences of the treatment centre. In
      selected Stage III adenocarcinomas, especially from the lower oesophagus,
      neoadjuvant chemotherapy (with post-operative chemotherapy when feasible) may
      induce tumour regression, which may facilitate surgical resection and improve
      survival rates, as has been demonstrated for cancers of the oesophagogastric
      junction.

PMID- 18070698
TI  - The multidisciplinary management of gastrointestinal cancer. Multimodal treatment
      of gastric cancer.
AB  - Although radical surgical R0 resections are the basis of cure for gastric cancer,
      surgery alone only provides long-term survival in 20-30% of patients with
      advanced-stage disease. Thus, in Western and European countries, advanced gastric
      cancer has a high risk of recurrence and metachronous metastases. Very recently,
      multimodal strategies combining different neoadjuvant and/or adjuvant protocols
      have improved the prognosis of gastric cancer when combined with surgery with
      curative intent. As used in palliative regimens, the combination of cisplatin
      with intravenous or oral fluoropyrimidines has been the integral component of
      such (neo)adjuvant strategies. However, the cytotoxic agents docetaxel,
      oxaliplatin and irinotecan and new targeted biologicals such as cetuximab,
      bevacizumab or panitumumab are currently under investigation, with or without
      irradiation, in multimodal treatment regimens. These studies may further increase
      R0 resection rates, and prolong disease-free and overall survival times in the
      treatment of advanced gastric cancer. This article reviews the most relevant
      literature on multimodal treatment of gastric cancer, and discusses future
      strategies to improve locoregional failures.

PMID- 18070699
TI  - The multidisciplinary management of gastrointestinal cancer. The diagnostic and
      therapeutic approach for primary solid liver tumours in adults.
AB  - The finding of a focal solid liver lesion represents a challenge for the
      clinician in terms of the most optimal diagnostic and therapeutic algorithm.
      Tumours may arise from hepatocytes (hepatocellular adenoma, dysplastic nodules
      and carcinoma), bile ducts (cholangiocarcinoma) or mesenchymal tissue
      (hemangioma, epithelioid haemangioendothelioma), or are metastases from primary
      tumours outside the liver. Focal nodular hyperplasia is the most frequent tumour
      like lesion. Imaging techniques are able to detect and characterise most lesions.
      However, small hypervascular lesions in a cirrhotic liver may be difficult to
      characterise. More insight has been gathered recently in the histological
      classification of hepatocellular adenomas, but the differential diagnosis by
      imaging of adenoma versus FNH or well-differentiated hepatocellular carcinoma
      remains often difficult. The therapy of a focal liver lesion is determined by its
      natural history and the functional status of the surrounding liver parenchyma.
      Selected patients with primary liver cancer are candidates for liver
      transplantation, while patients with advanced malignant tumours have a poor
      outcome.

PMID- 18070700
TI  - The multidisciplinary management of gastrointestinal cancer. Pancreatic cancer:
      from pathogenesis to cure.
AB  - Pancreatic cancer is the fourth leading cause of cancer-related death in the USA.
      The disease has a high mortality rate and the 5-year survival rate is estimated
      to be 4%. Currently, surgical resection is only possible in 20% of patients; even
      then, the overall 5-year survival rate is only 25%. As such, surgical therapy
      alone is not sufficient for pancreatic carcinoma, and prospective investigation
      of additional modalities is crucial. Numerous negative trials have shown that
      chemotherapy alone is the standard of care after resection of pancreatic
      carcinoma. However, results remain poor and progress with new drugs is needed in
      this setting. For locally advanced disease, the situation is more complicated;
      the ideal chemoradiation schedule has not been clearly defined, and improvements
      could come in the near future from the use of new radiotherapy tools and targeted
      therapies. For advanced disease, chemotherapy alone has given very disappointing
      results. A multidisciplinary approach combining biological assessment of targets
      with clinical trials to evaluate new targeted drugs should be considered.

PMID- 18070701
TI  - The multidisciplinary management of gastrointestinal cancer. Biliary tract
      cancers: from pathogenesis to endoscopic treatment.
AB  - Cholangiocarcinoma is the second most common hepatobiliary tumour. Even if it is
      a rare tumour, its incidence is increasing over these last decades, probably due
      in part to a better knowledge of the disease and to an improvement of the
      diagnosis. Accurate diagnosis and staging are key steps to determine the
      appropriate treatment. The only curative treatment of this cancer is surgical
      resection. To date, no neoadjuvant or adjuvant treatments have ever proved any
      survival benefit, and are not recommended outside clinical trials. Liver
      transplantation (with or without neoadjuvant treatment) can be an option for
      highly selected cases. Unfortunately, these tumours are generally diagnosed at an
      advanced stage or are unresectable. For most of these patients, palliative
      therapeutic options exist and are in further development, based on multimodal
      promising combinations including chemotherapy, targeted agents, radiation,
      endoscopic stenting and photodynamic treatment.

PMID- 18070702
TI  - The multidisciplinary management of gastrointestinal cancer. Colorectal cancer
      screening.
AB  - Colorectal cancer is a worldwide problem having global increases in the number of
      cases and deaths because of the expanding and aging of the population in both
      developing and developed countries. Screening methods are available which can
      reduce the incidence by removal of adenomas and can reduce deaths in diagnosed
      cancer cases by earlier stage detection. Faecal occult blood testing has the
      strongest proof of effectiveness based on randomised control trials;
      sigmoidoscopy has lesser proof based on case control studies, and barium enema
      the weakest proof of effectiveness. Screening colonoscopy has not been subjected
      to a randomised trial but there is now considerable evidence of its performance
      and safety and it has the ability to screen, diagnose, and treat (polypectomy) in
      one test and it is becoming increasingly offered. Many guidelines are now in
      place, all with positive a position on the effectiveness of screening. However,
      screening rates are low and many barriers are present that need to be overcome in
      order to make a major global impact on colorectal cancer incidence and mortality.

PMID- 18070703
TI  - The multidisciplinary management of gastrointestinal cancer. Multimodal treatment
      of rectal cancer.
AB  - Greater understanding of the natural history of rectal cancer, and the knowledge
      that a histologically involved circumferential margin due to inadequate lateral
      dissection confers a high risk of local recurrence have driven technical advances
      in surgical technique with meticulous surgical dissection along embryological
      planes. Significant improvements in local control and overall survival have been
      seen for patients with resectable rectal cancer. However, even high-quality
      surgery cannot always achieve a curative resection for locally advanced cancers
      that extend below the levators, having transgressed the mesorectal fascia.
      Magnetic resonance imaging is now accepted as a practical method of clinical
      staging, and can accurately predict pre-operatively the likelihood of achieving a
      clear circumferential margin. Technological advances in radiation planning and
      new effective cytotoxic drugs also give scope for dealing with unresectable
      rectal cancer, and the potential for controlling distant micrometastases. Hence,
      modern multimodal treatment of rectal cancer attempts to integrate surgery,
      radiotherapy and chemotherapy, and address the two distinct problems of local
      recurrence and metastatic disease. Multidisciplinary teams achieve the best
      results. This paper discusses the surgical management of rectal cancer, the
      pathology, the principles of imaging, and the lessons learnt from randomized
      trials of radiotherapy and chemoradiation.

PMID- 18070704
TI  - The multidisciplinary management of gastrointestinal cancer. The use of molecular
      markers in the diagnosis and treatment of colorectal cancer.
AB  - Rapidly growing insights into the molecular biology of colorectal cancer led to
      high hopes for the identification of molecular markers to be used in optimised
      and tailored treatment regimens for this disorder. However, no molecular marker
      has yet made it into daily practice. In this review we will discuss some of the
      potential molecular markers, focus on the lessons learnt from marker development
      and identify strategies for the future.

PMID- 18070705
TI  - The multidisciplinary management of gastrointestinal cancer. The integration of
      cytotoxics and biologicals in the treatment of metastatic colorectal cancer.
AB  - The management of patients with metastatic colorectal cancer (CRC) has changed
      dramatically over the last five years, with increasing chances of prolonged
      survival. The development of new drugs has contributed to the better outcome of
      patients with metastatic colorectal cancer. Until the mid-1990s the only
      available drug, with limited activity in metastatic CRC, was 5-fluorouracil (5
      FU). The development of the cytotoxic agents irinotecan, oxaliplatin and
      capecitabine and of the monoclonal antibodies against the vascular endothelial
      growth factor (VEGF) bevacizumab and against the epidermal growth factor receptor
      (EGFR) cetuximab and panitumumab have clearly increased the therapeutic options
      and have improved the outcome for patients with metastatic colorectal cancer.
      However, their introduction also raises many new questions and challenges.

PMID- 18070706
TI  - New insights into the biology and advances in the management of multiple myeloma.

PMID- 18070708
TI  - The malignant clone and the bone-marrow environment.
AB  - Multiple myeloma (MM) is characterized by the clonal expansion of monoclonal
      immunoglobulin-secreting plasma cells within the bone marrow (BM). It has become
      clear that the intimate reciprocal relationship between the tumor cell clone and
      the niches of the BM microenvironment plays a pivotal pathophysiologic role in
      MM. We and others have identified several new molecular targets and derived novel
      therapies which induce cytotoxicity against MM cells in the BM milieu, including
      thalidomide, bortezomib, and lenalidomide. Importantly, these agents induce tumor
      cell death, as well as inhibit MM-cell-BM-stromal-cell (BMSC) adhesion and
      related tumor-cell growth, survival, and migration. Moreover, they block both
      constitutive and MM-cell binding-induced growth factor and cytokine secretion in
      BMSCs. Further, they also block tumor angiogenesis and can augment anti-MM
      immunity. Although all three of these agents are now FDA-approved to treat MM,
      patients inevitably relapse, and further improvements remain urgently needed.
      Here we review our current knowledge of the MM cell clone, as well as the impact
      of the BM microenvironment on tumor-cell growth, survival, migration and drug
      resistance. Delineating the mechanisms and sequelae of the reciprocal
      relationship between the MM cell clone, distinct BM extracellular matrix
      proteins, and accessory cell compartments may provide the basis for new effective
      therapeutic strategies to re-establish BM homeostasis and thereby improve MM
      patient outcome.

PMID- 18070707
TI  - Genetic events in the pathogenesis of multiple myeloma.
AB  - The genetics of myeloma has been increasingly elucidated in recent years.
      Recurrent genetic events, and also biologically distinct and clinically relevant
      genetic subtypes of myeloma have been defined. This has facilitated our
      understanding of the molecular pathogenesis of the disease. In addition, some
      genetic abnormalities have proved to be highly reproducible prognostic factors.
      With the expanding therapeutic armamentarium, it is time to include genetic
      assessment as part of clinical evaluation of myeloma patients to guide
      management. In this review we examine the role of various genetic abnormalities
      in the molecular pathogenesis of myeloma, and the use of such abnormalities in
      disease classification, prognosis and clinical management.

PMID- 18070709
TI  - Pathophysiology of myeloma bone disease.
AB  - Multiple myeloma is a tumor of terminally differentiated plasma cells that home
      to and expand in the bone marrow. It is the second most common hematologic
      malignancy, with approximately 16,000 new cases per year, and accounts for an
      estimated 11,000 deaths in the USA. It is the most common cancer to metastasize
      to bone, with up to 90% of patients developing bone lesions. The bone lesions are
      purely osteolytic in nature, and up to 60% of patients develop a pathologic
      fracture over the course of their disease. Bone disease is a hallmark of multiple
      myeloma, and the bone disease differs from other bone metastasis caused by other
      tumors. Although both myeloma and other osteolytic metastasis induce increased
      osteoclastic bone resorption, in contrast to other tumors, osteoblast activity in
      myeloma is either severely decreased or absent. The basis for this severe
      imbalance between increased osteoclastic bone resorption and decreased bone
      formation resulting from suppressed osteoblastic activity has been a topic of
      extensive investigation during the last several years. The clinical consequences
      of this extensive accelerated and imbalanced bone destruction process include
      bone pain, pathologic fractures, hypercalcemia and spinal cord compression
      syndromes, which can be devastating for patients and significantly impact overall
      quality of life and expected survival. In this chapter, we will discuss the
      pathophysiology underlying bone disease in myeloma. This results from the
      uncoupling of bone remodeling and is characterized by markedly increased activity
      of osteoclasts and profound decreased activity of osteoblasts. In addition, we
      also review the emerging data on novel targeted therapies aimed at ameliorating
      myeloma bone disease.

PMID- 18070710
TI  - Role of genetics in prognostication in myeloma.
AB  - As in other hematological malignancies, cytogenetics is becoming a major
      prognostic parameter in myeloma. Myeloma differs from other hemopathies
      particularly in technical aspects related to low proliferation and partial
      infiltrates. Thus, fluorescence in-situ hybridization (FISH) is probably the best
      method for cytogenetic assessment in myeloma, but it requires the identification
      of the malignant cells (morphologically, immunologically or through sorting).
      Several chromosomal abnormalities have been identified. Among them, the t(4;14)
      and t(14;16) translocations and the del(17p) are the most important for outcome
      prediction, all of them predicting a short overall survival. However, even in
      these genetically defined subgroups, an outcome heterogeneity is observed,
      suggesting the role of other factors (genetic or otherwise) in disease evolution.

PMID- 18070711
TI  - Epidemiology of the plasma-cell disorders.
AB  - This review of the plasma-cell disorders begins with the definition of monoclonal
      gammopathy of undetermined significance (MGUS). The prevalence of MGUS in white
      and black populations is described. MGUS is a common finding in the medical
      practice of all physicians, and thus it is important to both the patient and the
      physician to determine whether the monoclonal protein remains stable or
      progresses to multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM),
      primary systemic amyloidosis (AL), or a related disorder. The long-term (almost
      40 years) follow-up data of 241 patients in the Mayo Clinic population is
      provided. In a large study of 1384 patients with MGUS from southeastern
      Minnesota, the risk of progression to MM, WM, AL, or other disorders was
      approximately 1% per year. Risk factors for progression are provided. The
      incidence of MM in Olmsted County, Minnesota, remained stable for the 56-year
      span 1945-2001. The apparent increase in incidence and mortality rates among
      patients with MM in many studies is due to improved case ascertainment,
      especially among the elderly. The incidence and mortality rates of MM in the
      United States and other countries are presented. The major emphasis is on the
      cause of MM, which is unclear. Exposure to radiation from atomic bombs,
      therapeutic and diagnostic radiation, and in workers in the nuclear industry
      field are addressed. Many studies involving agricultural occupations, exposure to
      benzene, petroleum products, and engine exhaust and other industrial exposures
      are discussed. Tobacco use, obesity, diet, and alcohol ingestion are all possible
      causes of MM. Clusters of MM have been noted. Multiple cases of MM have been
      found in first-degree relatives.

PMID- 18070712
TI  - Multiple myeloma: new staging systems for diagnosis, prognosis and response
      evaluation.
AB  - Multiple myeloma must be distinguished from monoclonal gammopathy of undetermined
      significance (MGUS), smoldering multiple myeloma (SMM), and several other closely
      related plasma-cell disorders. In recent years, new systems have emerged for
      diagnosis, staging, and risk stratification of myeloma. The criteria recommended
      are primarily derived from the International Myeloma Working Group, with certain
      updates and clarifications. The International Staging System (ISS) is the
      standard for staging of myeloma. However, for therapeutic purposes, a risk
      stratification model is used to define high-risk patients who can benefit from
      novel therapeutic strategies. The International Myeloma Working Group uniform
      response criteria have been developed as the standard for response assessment in
      current and future clinical trials. The criteria incorporate the category 'very
      good partial response' (VGPR) which, given its importance in predicting outcome
      following therapy, should be reported in all trials; such reporting will also
      enable better comparisons between therapies.

PMID- 18070713
TI  - Thalidomide in the treatment of multiple myeloma.
AB  - Thalidomide--either alone or in combination with dexamethasone or chemotherapy-
      has shown significant activity in relapsed/refractory disease. When used in the
      induction regimens in untreated patients, it significantly increases the response
      rates as well progression-free survival. Moreover, thalidomide as a maintenance
      therapy has become a very attractive option. However, the toxicity profile of the
      drug, mainly neurotoxicity and thrombotic events, mandate careful monitoring of
      patients treated with thalidomide, whether as the first line, in the relapsed
      setting, or as maintenance. In this chapter we will review the pharmacology,
      mechanisms of action, and toxicity of the drug, and will focus on available data
      from clinical experience and randomized trials of thalidomide in the different
      settings of multiple myeloma: refractory/relapsed disease, upfront treatment in
      patients who are eligible for high-dose therapy as well as those who are not, and
      finally the use of thalidomide as a maintenance treatment.

PMID- 18070714
TI  - Bortezomib in multiple myeloma.
AB  - Multiple myeloma (MM) remains an incurable disease, and novel agents are
      therefore needed to improve outcome. Bortezomib is the first proteasome inhibitor
      to be approved by the US Food and Drug Administration and the European Agency for
      the Evaluation of Medicinal Products for the treatment of refractory/relapsed MM.
      Bortezomib has demonstrated significant anti-myeloma activity as a single agent
      in refractory/relapsed MM. When used in combination with other agents, responses
      have suggested the possibility of chemosensitization and synergy. All these facts
      have been the rationale for the use of bortezomib-based regimens as upfront
      treatment in young and elderly newly diagnosed MM patients. Furthermore,
      bortezomib does not appear to have an adverse effect on subsequent stem-cell
      collection. Bortezomib is well tolerated; most side-effects are only mild to
      moderate and manageable. Practical management of these side-effects is given so
      that they can be recognized and minimized by dose modification or concomitant
      therapy.

PMID- 18070715
TI  - Lenalidomide in multiple myeloma.
AB  - For many years the treatment of multiple myeloma was limited to such regimens as
      melphalan-prednisone, high-dose dexamethasone, and vincristine-doxorubicin
      dexamethasone (VAD). These combinations provided response rates of 45-55%, with
      complete remission rates of up to 10%. With the advent of thalidomide- and
      bortezomib-based combinations, response rates to induction therapy have risen to
      85-95% in previously untreated patients and are associated with complete
      remission rates up to 25%. However, these agents are associated with such side
      effects as somnolence, constipation and neuropathy. Lenalidomide, a thalidomide
      analog, was developed with the hope of improving both the efficacy and toxicity
      profile of thalidomide, and has subsequently shown significant clinical activity
      in patients with multiple myeloma. We describe the role of lenalidomide in
      patients with symptomatic multiple myeloma that is newly diagnosed, relapsed
      and/or refractory to other therapies, or concurrent with primary amyloidosis.

PMID- 18070716
TI  - Frontline treatment in multiple myeloma patients not eligible for stem-cell
      transplantation.
AB  - Melphalan-prednisone-thalidomide (MPT) currently appears to be the treatment of
      choice for a large proportion of elderly patients ineligible for autologous stem
      cell transplantation (ASCT). It seems certain that in the near future melphalan
      prednisone-Velcade (MPV) and melphalan-prednisone-lenalidomide (MPR) will also be
      proved superior to melphalan-prednisone (MP), thus providing three therapeutic
      options (MPT, MPV and MPR) in this patient group with multiple myeloma (MM).
      These therapeutic options could lead to more personalized treatment approaches,
      based on patient comorbidities, as the three novel therapies have somewhat
      different toxicity profiles. MP would be appropriate for only a minority of
      patients with poor performance status and/or significant comorbidities, such as
      severe neuropathy or a contraindication to anticoagulants. Questions regarding
      the relative efficacy of melphalan-based regimens versus dexamethasone-based
      regimens (preferably with low-dose dexamethasone) will require randomized phase
      III trials. More intensive approaches with new drug combinations or with the
      incorporation of polyethylene glycolated (PEGylated) liposomal doxorubicin will
      also require additional studies. Additionally, the important issue of maintenance
      treatment needs to be further investigated, especially in elderly patients.

PMID- 18070717
TI  - Role of autologous stem-cell transplantation in multiple myeloma.
AB  - Multiple myeloma (MM) is one of the diseases in which the impact of dose
      intensity has been demonstrated. Consequently, in 2005 MM was the first disease
      for which autologous stem-cell transplantation (ASCT) was indicated in Europe and
      the US. However, ASCT is not curative, and most patients relapse in a median of 3
      years. The introduction of novel agents such as thalidomide, bortezomib (Velcade)
      or lenalidomide (Revlimid) was logical to try to improve the high-dose strategy,
      and promising results have been reported. This article will focus on the current
      results of ASCT and will discuss the main research area to try to improve this
      strategy.

PMID- 18070718
TI  - The Arkansas approach to therapy of patients with multiple myeloma.
AB  - This chapter gives an account of the experience of the Arkansas myeloma program
      since 1989 with transplant-supported high-dose melphalan, novel agents, and
      prognostic factors as they relate to standard laboratory features, gene
      expression profiling, and magnetic resonance imaging (MRI). Incorporation of
      novel agents and new concepts, such as post-tandem transplant consolidation
      therapy, has improved the rate and duration of complete response and prolonged
      event-free and overall survival rates. With Total Therapy 2, median survival
      exceeds 8 years, while Total Therapy 3 with added bortezomib has sustained
      complete remissions in more than 90% of patients at 2 years which, when used as a
      survival surrogate in Total Therapy 2, assured a high 6-year survival rate of
      75%. Gene expression profiling identified 15% of patients with very short
      survival. MRI-defined focal lesions are associated with poor outcome, while their
      resolution - although slower than the time course of attaining clinical complete
      remission - conferred superior survival. Representing a frequent source of
      recurrence, with genetic profiles (in both plasma and stromal cells) distinct
      from those in random bone-marrow samples, therapeutic efforts are directed at
      hastening onset and increasing frequency of focal lesion resolution.

PMID- 18070719
TI  - Is there still a role for allogeneic stem-cell transplantation in multiple
      myeloma?
AB  - Despite significant improvements in survival for multiple myeloma patients
      through autologous stem-cell transplantation (SCT) and the introduction of novel
      drugs, the disease remains incurable for all but a small fraction of patients.
      Only allogeneic SCT is potentially curative, due in part to a graft-versus
      myeloma effect. High transplant-related mortality with allogeneic SCT is
      currently the major limitation to wider use of this potentially curative
      modality. Mortality can be reduced through the use of lower-intensity
      conditioning regimens which allow engraftment of allogeneic stem cells, but this
      comes at a cost of higher rates of disease progression and relapse. Promising
      studies to improve outcomes of allogeneic transplants include the use of more
      intensive non-myeloablative conditioning regimens, tandem transplants, peripheral
      blood cells, graft engineering to improve the graft-versus-myeloma activity while
      reducing graft-versus-host disease (GVHD), post-transplant maintenance, and
      targeted conditioning therapies such as bone-seeking radioisotopes.

PMID- 18070721
TI  - Supportive care in multiple myeloma.
AB  - In myeloma bone disease, bisphosphonates have been shown to delay the progression
      of osteolytic lesions and prevent fractures. In the case of painful vertebral
      fractures, vertebroplasty and kyphoplasty have become standard procedures to
      control symptoms and restore the original height of the vertebrae. Adequate pain
      control is of crucial importance for the quality of life of myeloma patients, as
      is maintaining adequate hemoglobin levels with the use of erythropoietic growth
      factors. Infections should be treated aggressively in myeloma patients, as these
      contribute significantly to morbidity and mortality. In patients with repeated
      infectious complications, prophylactic measures such as long-term application of
      antibiotic or antiviral medication or use of intravenous immunoglobulins is
      recommended. The concerted action of these supportive therapies can significantly
      improve the wellbeing of myeloma patients in phases of disease progression as
      well as during phases of remission. In progressive disease, certain measures such
      as adequate pain control and radiotherapy can ameliorate symptoms until the
      therapeutic effect of systemic anti-neoplastic therapy becomes evident.

PMID- 18070723
TI  - Postoperative antibiotic therapy for children with perforated appendicitis: long
      course of intravenous antibiotics versus early conversion to an oral regimen.
AB  - BACKGROUND: Although treatment for nonperforated acute appendicitis is usually
      straightforward, the optimal treatment of patients with perforated appendicitis
      remains controversial. METHODS: Our institution performed a 2.5-year
      retrospective review of outcomes for postoperative treatment of perforated
      appendicitis. Patients were treated with either short-term intravenous (IV)
      antibiotic therapy and conversion to PO antibiotics (PO group) or long-term
      antibiotic therapy by way of a peripherally inserted central venous catheter (IV
      group). RESULTS: One-hundred forty-nine patients with a diagnosis of perforated
      appendicitis were reviewed. There were 47 patients in the PO group and 102
      patients in the IV group. In the IV group, there were 2 intra-abdominal abscesses
      (2%) requiring readmission; there were also 2 intra-abdominal abscesses in the PO
      group (4.2%). Outpatient conversion to PO antibiotics resulted in an average
      savings of approximately $4,000/patient. CONCLUSIONS: Inpatient IV antibiotic
      therapy followed by outpatient conversion to PO antibiotics is a safe and cost
      effective treatment of perforated appendicitis.

PMID- 18070722
TI  - Use of organotypic coculture to study keloid biology.
AB  - BACKGROUND: Keloids are pathologic scars afflicting a large segment of our
      population and for which there is no definitive therapy. The lack of an animal
      model for keloid formation has hampered study. We developed an in vitro
      organotypic skin model to simulate normal keloid biology, which may allow us to
      study keloid formation without an animal model. METHODS: Normal (NFs) and keloid
      (KFs) human fibroblasts were cultured in a collagen matrix to create a 3
      dimensional dermal structure. Normal human keratinocytes (NKs) were cultured as a
      second layer on top and exposed to an air-fluid interface to allow
      differentiation into a mature keratinocyte layer. The organotypic skin was
      maintained for 28 days in Dulbecco's modified eagle medium with 10% fetal calf
      serum. Samples were collected, processed, sectioned, stained with hematoxylin and
      eosin, and then measured for qualitative analysis. alpha-smooth-muscle actin was
      also evaluated by immunoblotting. RESULTS: KF/NK organotypic skin showed
      increased collagen deposition, based on significantly denser collagen staining,
      with increased dermal thickness compared with NF/NK organotypic skin. We saw
      increased contracture in the KF/NK construct, and this correlated with increased
      organization of alpha-smooth-muscle actin fibers in the dermal layer of KF/NK
      organotypic skin compared with NF/NK skin. CONCLUSIONS: We have shown that
      coculture of KFs with keloid keratinocytes leads to an increased collagen
      production and dermal contracture compared with NFs and NKs, consistent with
      known keloid behavior. Given the lack of an animal model, we believe that
      organotypic skin culture can serve as a surrogate to study keloid formation.

PMID- 18070720
TI  - From the bench to the bedside: emerging new treatments in multiple myeloma.
AB  - Within the last decade, several novel classes of anti-myeloma therapeutics have
      become available. The clinical successes achieved by thalidomide, lenalidomide,
      and the proteasome inhibitor bortezomib, and in particular the ability of these
      agents to lead to major clinical responses in patients resistant to conventional
      or high-dose chemotherapy, have highlighted the importance of expanding further
      the spectrum of classes of agents utilized for the treatment of myeloma. Herein,
      we review the current status for the development of novel anti-myeloma agents,
      with emphasis on classes of therapeutics which have already translated into
      clinical trials or those in advanced stages of preclinical development. These
      include second-generation proteasome inhibitors (NPI-0052 and PR-171), heat shock
      protein 90 (hsp90) inhibitors, 2-methoxyestradiol, histone deacetylase (HDAC)
      inhibitors (e.g. SAHA and LBH589), fibroblast growth factor receptor 3 (FGF-R3)
      inhibitors, insulin-like growth factor 1 receptor (IGF-1R) inhibitors, mTOR
      inhibitors, monoclonal antibodies, and agents specifically targeting the tumor
      microenvironment, such as defibrotide.

PMID- 18070724
TI  - Wandering spleen with chronic torsion.
AB  - Wandering spleen, a rare clinical entity with a high incidence of splenic torsion
      and infarction, was preoperatively diagnosed in a 28-year-old woman. Axial
      computed tomography showed the absence of the spleen in the left subphrenic space
      and a spleen-like mass in the pelvis, suggestive of a wandering spleen. A coronal
      contrast-enhanced computed tomography image exhibited the enlarged spleen
      suspended by elongated, dilated, and somewhat tortuous splenic vessels. Owing to
      the symptomatic splenomegaly with hypersplenism and chronic torsion, laparoscopic
      splenectomy was performed.

PMID- 18070725
TI  - Effects of intestinal electrical stimulation on postprandial small-bowel motility
      and transit in dogs.
AB  - BACKGROUND: Intestinal electrical stimulation (IES) with long pulses has been
      reported to inhibit motility as well as accelerate transit of continuous
      infusion. However, it is unknown whether there is a correlation between the IES
      induced alterations in motility and transit and whether there is a difference in
      transit during IES between continuous infusion and bolus infusion. METHODS: The
      study was performed in 2 postprandial sessions (control and stimulation) in dogs
      with 2 pairs of serosal electrodes and 2 intestinal cannulas. Intestinal motility
      and transit with and without IES were measured by manometry and phenol red,
      respectively. RESULTS: IES significantly decreased intestinal motility and
      increased transit time. There was a significant correlation between motility
      index and transit during IES. CONCLUSIONS: IES inhibits both intestinal bolus
      motility and transit. There is correlation between motility and transit during
      IES.

PMID- 18070726
TI  - Judgment analysis: a method for quantitative evaluation of trainee surgeons'
      judgments of surgical risk.
AB  - BACKGROUND: Surgical judgment and decision making require valid methods of
      assessment. The aim of this study was to evaluate the use of judgment analysis as
      a technique for quantitative evaluation of surgeons' risk estimates. METHODS:
      Thirty trainee surgeons' estimates of conversion risk in laparoscopic
      cholecystectomy were investigated using judgment analysis. Hypothetical cases
      were created, differing in relevant risk factors. Twenty repeat cases were
      incorporated to test for reliability. Surgeons' estimates were compared with an
      outcome-derived gold standard from the published literature. RESULTS: The mean
      reliability was .77 (range, .47-.98), and regression models indicating the
      weighting of variables had a mean adjusted R(2) value of .53 (range, .12-.76).
      Variables were subject to wide variation in weighting. The mean correlation to
      the gold standard model was .48 (range, .08-.72). CONCLUSIONS: Judgment analysis
      allows detailed quantitative evaluation of the consistency of surgeons' risk
      estimates and the influence of different variables on them. Comparison with a
      gold standard model enables accuracy to be measured.

PMID- 18070727
TI  - Effective instruction of vascular anastomosis in the surgical skills laboratory.
AB  - BACKGROUND: A greater emphasis has recently been placed on laboratory-based
      training of core surgical skills and tasks, such as vascular anastomosis. Despite
      this emphasis, little objective data exist regarding the effectiveness of
      vascular anastomosis instruction in the laboratory setting. METHODS: Residents of
      all postgraduate levels received laboratory-based vascular anastomosis training.
      Each individual fashioned an end-to-side anastomosis between synthetic graft and
      porcine aorta before instruction (pretest). All subjects then received
      standardized anastomosis training with practice time. After training, the
      anastomosis was then repeated (posttest). Metrics included time to completion,
      anastomotic leakage, and visual characteristics of the completed product.
      RESULTS: Postteaching improvement was demonstrated by all residents (n = 32).
      Posthoc analysis showed statistically significant improvements in junior
      residents only. CONCLUSIONS: Laboratory-based training can effectively improve
      the ability of residents to perform vascular anastomosis immediately after
      training. Junior residents may gain a greater advantage from laboratory teaching.

PMID- 18070728
TI  - Comparison of clinical characteristics at diagnosis and during follow-up in 118
      patients with Hurthle cell or follicular thyroid cancer.
AB  - BACKGROUND: Hurthle cell cancer (HCC) is considered by some to be a variant of
      follicular cancer (FC), but many think it is a distinct histologic tumor with a
      more aggressive behavior. METHODS: The influence of age at diagnosis, tumor
      stage, gender, and extent of operation on disease-free interval and cause
      specific mortality at 5 and 10 years after initial thyroidectomy was analyzed.
      RESULTS: The 10-year disease-free interval was 75% for FC and 40.5% for HCC (P =
      .08). The 10-year cause-specific mortality was 20% for FC patients and 51% for
      HCC (P = .2). The risk factors for HCC progression and survival were
      extrathyroidal invasion, presence of metastases at diagnosis, male gender, and
      extent of thyroidectomy, whereas for FC, the only significant risk factors were
      extrathyroidal invasion and presence of metastases at diagnosis. CONCLUSION:
      Patients with HCC have more aggressive tumors than patients with FC. Our data
      suggest that FC and HCC should be classified as distinct tumors.

PMID- 18070729
TI  - Do novices display automaticity during simulator training?
AB  - BACKGROUND: The objective of this study was to investigate whether novices
      improve their ability to develop multitask (ie, automaticity) with accumulating
      experience on a simulated laparoscopic task. METHODS: In this prospective study,
      novices (12 premed students) trained for 4 months in laparoscopic suturing.
      Simultaneously with suturing, participants performed a visual-spatial secondary
      task to assess their spare attentional capacity. Trainees were required to
      achieve expert-derived levels in both suturing (520 score) and the secondary task
      (target 73%). Their performance was assessed with objective scores, and their
      ability to multitask during training was examined. RESULTS: After 10 +/- 5 hours
      and 84 +/- 41 repetitions, participants demonstrated improvements in their
      suturing (70%, P < 0.001) and secondary-task performance (16%, P = 0.08) compared
      with their baseline scores. During the study period, 11 of 12 participants
      achieved suturing proficiency, but no one achieved secondary-task proficiency.
      Longer training times correlated with higher secondary-task scores (r = .68, P <
      0.02), and participants who performed >100 repetitions (n = 4) achieved higher
      secondary-task scores (P < 0.03). COMMENTS: This study provides evidence for
      improved automaticity at advanced stages of simulator training. Although novices
      achieve simulator proficiency after relatively short training durations, the
      attainment of automaticity requires substantially longer training periods.
      Further study of this concept is warranted and is currently underway.

PMID- 18070730
TI  - Does delaying repair of an asymptomatic hernia have a penalty?
AB  - BACKGROUND: The incidence of hernia accident for inguinal hernias in men who are
      minimally symptomatic is sufficiently low that watchful waiting is an acceptable
      alternative to routine repair. Our aim was to determine whether a delay in hernia
      surgery affects short- and long-term outcomes. METHODS: Patients from a
      multicenter randomized clinical trial of immediate tension-free repair versus
      watchful waiting for minimally symptomatic inguinal hernias were studied.
      Patients (n = 353) underwent tension-free repair and were classified as immediate
      repair (< or = 6 months, N = 288) or delayed repair (> 6 months, N = 65).
      RESULTS: Patients were similar at baseline with respect to age, American Society
      of Anesthesiologists classification, pre-existing conditions, hernia type, and
      hernia characteristics. Patients undergoing immediate and delayed repair had
      comparable surgical time, surgical complications, recurrence rates, and
      satisfaction with outcome. Multivariate analyses found no relation between
      duration until hernia repair and operative time, incidence of complications, long
      term pain, or functional status. CONCLUSIONS: Delaying hernia repair in patients
      who are minimally symptomatic does not have an adverse effect on subsequent
      operation and on other outcomes.

PMID- 18070731
TI  - Laparoscopic Nissen fundoplication with anterior versus posterior hiatal repair:
      long-term results of a randomized trial.
AB  - BACKGROUND: Postoperative dysphagia in patients after Nissen fundoplication might
      be related to the technique used for the closure of the esophageal hiatus.
      METHODS: A total of 102 patients with gastroesophageal reflux were randomized to
      undergo laparoscopic Nissen fundoplication with either anterior (47 patients) or
      posterior (55 patients) repair of the diaphragmatic hiatus. RESULTS: Clinical
      data at 5 years after surgery were available for 96% of patients enrolled in the
      trial. There was no significant difference between the 2 techniques for symptoms
      of dysphagia at the 5-year follow-up evaluation, although more patients who
      underwent posterior hiatal repair underwent further surgery for dysphagia-related
      symptoms (8 vs 2). Better control of heartburn was achieved in patients in the
      anterior hiatal repair group. Patients from both groups were equally satisfied
      with the overall outcome after surgery. CONCLUSIONS: At the 5-year follow-up
      evaluation, there was no significant difference in dysphagia between anterior
      closure and posterior hiatal repair.

PMID- 18070732
TI  - Surgical treatment of sternoclavicular joint infections in cirrhotic patients.
AB  - BACKGROUND: Cirrhotic patients with sternoclavicular joint (SCJ) infection pose a
      unique challenge for which there are no management guidelines. We reviewed our
      experience with this unusual infection in this high-risk patient population.
      METHODS: We performed a retrospective analysis of all patients with cirrhosis (n
      = 5) treated surgically for SCJ infection from January 1998 to July 2006.
      RESULTS: All infections were locally advanced with bone necrosis, complex abscess
      formation, or mediastinal involvement. En bloc SCJ resection was performed in 3
      patients. A more conservative approach of incision and drainage with debridement
      was performed in 2 patients. Sepsis and/or pulmonary compromise occurred in all
      patients postoperatively and the surgical mortality rate was 40%. All deaths
      occurred after en bloc SCJ resection. CONCLUSIONS: Sternoclavicular joint
      infections in cirrhotic patients tend to be extensive in nature and pose a high
      surgical risk. Adequate surgical drainage and debridement may be better tolerated
      than a radical en block resection.

PMID- 18070733
TI  - Safe and quick distal pancreatectomy using a staggered six-row stapler.
AB  - BACKGROUND: The use of stapling devices for distal pancreatectomy remains
      controversial, due to concerns about the development of postoperative pancreatic
      fistula (POPF) and hemorrhage. METHODS: We report herein the usefulness of the
      Endo SGIA stapler (Tyco Healthcare, Norwalk, CT) for distal pancreatectomy by
      placing 2 triple-staggered rows, ie, 6 rows of staples in the pancreatic stump.
      The pancreas was divided together with both the splenic artery and vein with Endo
      SGIA in 7 consecutive hand-assisted laparoscopic distal pancreatectomies.
      RESULTS: No patients developed clinically significant POPF or postoperative
      hemorrhage. None of the patients had complications that may have influenced the
      length of hospital stay. CONCLUSION: The 6-row Endo SGIA stapler allows quick and
      effective prevention of POPF after distal pancreatectomy.

PMID- 18070734
TI  - Microporous polysaccharide hemospheres for management of laparoscopic trocar
      injury to the spleen.
AB  - BACKGROUND: Management of iatrogenic injuries during laparoscopy can be arduous.
      Recent advancements in surgical hemostatic agents have provided beneficial
      therapeutic alternatives. This project evaluates microporous polysaccharide
      hemospheres (MPH), with demonstrated efficiency achieving topical hemostasis, in
      the setting of intracorporeal laparoscopic splenic injury. METHODS: Four domestic
      female pigs were subjected to reproducible laparoscopic 12-mm and 5-mm trocar
      splenic injuries. Each surgery was an identical transperitoneal hand-assisted
      laparoscopic procedure. Hemostasis, or no bleeding after treatment, was achieved
      by measured dose applications of MPH. RESULTS: The MPH successfully achieved
      hemostasis for all splenic injuries except in 1 case, where a 12-mm lesion
      transected the splenic artery. The mean time to hemostasis, applications of MPH,
      and estimated blood loss for the 5- and 12-mm injuries were 165.3 +/- 45.7 and
      200.7 +/- 106.5 seconds, 1.3 +/- .5 applications for both, and 12.0 +/- 4.6 and
      17.7 +/- 9.1 g, respectively. CONCLUSIONS: MPH represents a powerful hemostatic
      agent that demonstrated complete hemostasis for iatrogenic splenic injury.

PMID- 18070735
TI  - Early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a meta
      analysis of randomized clinical trials.
AB  - BACKGROUND: The appropriate timing for laparoscopic cholecystectomy in the
      treatment of acute cholecystitis remains controversial. More recent evaluation
      indicates early laparoscopic surgery may be a safe option in acute cholecystitis,
      although conversion rates may be higher. No conclusive evidence establishing best
      practice in terms of clinical benefit exists. METHODS: All randomized clinical
      studies published between 1987 and 2006 comparing early versus delayed
      laparoscopic cholecystectomy for acute cholecystitis were analyzed, irrespective
      of language, blinding, or publication status. Exclusions were quasi-randomized
      trials, inadequate follow-up description, or allocation concealment. Endpoints
      included conversion rates, postoperative complications, total hospital stay, and
      operation time. Random and fixed-effect models were used to aggregate the study
      endpoints and assess heterogeneity. RESULTS: Four studies containing 375 patients
      were included. No significant study heterogeneity or publication bias was found.
      There was no significant difference in conversion rates (odds ratio = .915 [95%
      confidence interval (CI), .567-1.477], P = .718) and postoperative complications
      (odds ratio = 1.073 [95% CI, .599-1.477], P = .813) between both groups.
      Operation time was significantly reduced (weighted mean difference [WMD] = .412
      [95% CI, .149-.675], P = .002) with delayed cholecystectomy. The total hospital
      stay was significantly reduced (WMD = .905 [95% CI, .630-1.179], P = .0005) with
      early cholecystectomy. The postoperative stay was significantly reduced in the
      delayed group (WMD = .393 [95% CI, .128-.659], P = .004). CONCLUSIONS: These meta
      analysis data suggest that early laparoscopic cholecystectomy allows
      significantly shorter total hospital stay at the cost of a significantly longer
      operation time with no significant differences in conversion rates or
      complications.

PMID- 18070736
TI  - An axillary score (Barranger Score) to predict nonsentinel node metastasis in
      breast cancer patients with positive sentinel node.

PMID- 18070737
TI  - Training of general surgical residents: what model is appropriate?

PMID- 18070738
TI  - Visuo-spatial ability and fMRI cortical activation in surgery residents.

PMID- 18070739
TI  - Designer schools: the role of school space and architecture in obesity
      prevention.
AB  - Spatial features of obesogenic environments studied on a broad community level
      have been associated with childhood overweight and obesity, but little research
      has focused on the effects of the design of micro spaces, such as schools, on
      individual health behaviors. This article aims to generate thinking and research
      on the link between school space and architecture and obesity prevention by
      reviewing and synthesizing available literature in architecture, environmental
      psychology, and obesity research, in an effort to propose promising ideas for
      school space design and redesign. The school environment is defined through 5
      dimensions: physical, legal, policy, social, and cultural domains. Theories
      underlying environmental interventions and documented associations between the
      environment and health behaviors and outcomes are reviewed to illustrate how
      existing environmental research could translate to obesity prevention. Design
      strategies aimed at promoting physical activity and healthful eating are
      proposed, with particular emphasis on the design of cafeterias, activity spaces,
      connectivity with the larger community, and student health centers.

PMID- 18070740
TI  - No association between rs7566605 variant and being overweight in Japanese.
AB  - It has recently been demonstrated that a common single-nucleotide polymorphism
      (rs7566605) upstream of the transcription start site for the insulin-induced gene
      2 is associated with obesity in several European/European origin or African
      American cohorts. We tested whether this variant is also linked to overweight
      among Asian populations. Our sample included 2233 randomly selected, community
      dwelling, middle-age and older Japanese people (men, 1128; women, 1105; age, 40
      to 79 years; C allele frequency, 0.32). We observed that there were no
      differences in BMI levels [men, 22.9 +/- 0.3 (mean +/- standard error) vs. 22.9
      +/- 0.1, p = 0.820; women, 22.8 +/- 0.3 vs. 22.9 +/- 0.1, p = 0.792], waist
      circumferences and hip circumferences, waist-to-hip ratio, and fat mass between
      rs7566605 GG/GC and CC genotypes in both genders. In addition, logistic
      regression analysis, using age and sex as covariates, revealed no association of
      the single-nucleotide polymorphism with overweight (BMI >or=25) between rs7566605
      genotypes in the Japanese cohort (CC vs. CG/GG, odds ratio = 1.18; 95% confidence
      interval = 0.84 to 1.65, p = 0.333; CC vs. GG, odds ratio = 1.19, 95% confidence
      interval = 0.84 to 1.69, p = 0.325). No significant associations were observed
      between polymorphism and glucose or insulin levels. These results suggested no
      association of the rs7566605 variant with overweight in Japanese people.

PMID- 18070741
TI  - Metabolic syndrome in Yup'ik Eskimos: the Center for Alaska Native Health
      Research (CANHR) Study.
AB  - OBJECTIVE: This study investigated the prevalence of metabolic syndrome and its
      defining components among Yup'ik Eskimos. RESEARCH METHODS AND PROCEDURES: A
      cross-sectional study design that included 710 adult Yup'ik Eskimos >or=18 years
      of age residing in 8 communities in Southwest Alaska. The prevalence of metabolic
      syndrome was determined using the recently updated Adult Treatment Panel III
      criteria. RESULTS: The prevalence of metabolic syndrome in this study cohort was
      14.7%, and varied by sex with 8.6% of the men and 19.8% of the women having
      metabolic syndrome. This is lower than the prevalence of 23.9% in the general
      U.S. adult population. The most common metabolic syndrome components/risk factors
      were increased waist circumference and elevated blood glucose. High-density
      lipoprotein (HDL) cholesterol levels in Yup'ik Eskimos were significantly higher,
      and triglycerides lower than levels reported in National Health and Nutritional
      Examination III. DISCUSSION: Compared with other populations, metabolic syndrome
      is relatively uncommon in Yup'ik Eskimos. The higher prevalence among Yup'ik
      women is primarily explained by their large waist circumference, suggesting
      central body fat accumulation. Further increases in metabolic syndrome risk
      factors among Yup'ik Eskimos could lead to increases in the prevalence of type 2
      diabetes and cardiovascular disease, once rare in this population.

PMID- 18070742
TI  - BMI and seatbelt use.
AB  - OBJECTIVE: Seatbelt use among obese persons may be reduced because seatbelts are
      uncomfortable. We investigated the association between obesity and seatbelt use
      with data from the 2002 Behavioral Risk Factor Surveillance System Survey.
      RESEARCH METHODS AND PROCEDURES: Multivariable logistic regression was used to
      calculate odds ratios and 95% confidence intervals (CIs) for seatbelt use among
      overweight (BMI, 25.0 to 29.9), obese (BMI, 30.0 to 39.9), and extremely obese
      (BMI >or= 40.0) persons, relative to a non-overweight/non-obese reference group
      (BMI <or= 24.9), adjusted for age, race, gender, education, and state seatbelt
      law. RESULTS: Adjusted odds ratios for seatbelt use were 0.89 (95% CI, 0.85 to
      0.93) for overweight, 0.69 (0.66 to 0.73) for obese, and 0.45 (95% CI, 0.40 to
      0.50) for extremely obese persons. Interaction effects were evident for all
      covariates, with stronger associations between increasing BMI and decreasing
      seatbelt use for women, increasing age, higher education, and residence in states
      with a secondary seatbelt law. There was a linear decrease in seatbelt use with
      increasing BMI for all subgroups except persons 18 to 24 years old. DISCUSSION:
      Lack of seatbelt can be added to the list of risk factors associated with
      obesity. Effective preventive interventions are needed to promote seatbelt use
      among overweight and obese persons.

PMID- 18070743
TI  - Differences in basal energy expenditure and obesity.
AB  - OBJECTIVE: To assess the impact of differences in basal energy expenditure on
      adiposity. RESEARCH METHODS AND PROCEDURES: Statistical analysis was performed on
      a published database giving anthropometric and energy expenditure measurements
      for 433 women and 335 men. Published equations derived by multiple regression
      analysis were used to predict basal metabolic rates in women and in men as a
      function of age, weight, and height. The differences between the observed and
      predicted rates (i.e., the residuals) were computed and expressed in terms of
      percentage deviation from the predicted rates of basal energy expenditure (BEE).
      In addition, individual body fat contents were computed using equations based on
      National Health and Nutrition Examination Study 3 data relating to body fat
      content determined by bioimpedance to BMI. RESULTS: There is no correlation
      between percentage body fat content and deviations from predicted (which one
      would refer to as normal) BEE. DISCUSSION: It can be concluded that relatively
      high or relatively low rates of BEE do not influence body weights and adiposity
      in a statistically identifiable manner. This contradicts and challenges the
      widely held view that low resting metabolic rates promote the development of
      obesity.

PMID- 18070744
TI  - Macrophage-adipocyte interaction: marked interleukin-6 production by
      lipopolysaccharide.
AB  - OBJECTIVE: Recent studies suggested macrophages were integrated in adipose
      tissues, interacting with adipocytes, thereby exacerbating inflammatory
      responses. Persistent low-grade infection by gram-negative bacteria appears to
      promote atherogenesis. We hypothesized a ligand for toll-like receptor 4 (TLR4),
      bacterial lipopolysaccharide (LPS), would further exaggerate macrophage-adipocyte
      interaction. RESEARCH METHODS AND PROCEDURES: RAW264.7 macrophage cell line and
      differentiated 3T3-L1 preadipocytes were co-cultured using transwell system. As a
      control, each cell was cultured independently. After incubation of the cells with
      or without Escherichia coli LPS, tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6 production was evaluated. RESULTS: Co-culture of macrophages
      and adipocytes with low concentration of Escherichia coli LPS (1 ng/mL) markedly
      up-regulated IL-6 production (nearly 100-fold higher than that of adipocyte
      culture alone, p < 0.01), whereas TNF-alpha production was not significantly
      influenced. This increase was partially inhibited by anti-TNF-alpha neutralizing
      antibody. Recombinant TNF-alpha and LPS synergistically up-regulated IL-6
      production in adipocytes. However, this increase did not reach the level of
      production observed in co-cultures stimulated with LPS. DISCUSSION: A ligand for
      TLR-4 stimulates macrophages to produce TNF-alpha. TNF-alpha, thus produced,
      cooperatively up-regulates IL-6 production with other soluble factors secreted
      either from adipocytes or macrophages in these cells. Markedly up-regulated IL-6
      would greatly influence the pathophysiology of diabetes and its vascular
      complications.

PMID- 18070745
TI  - Quality of life in Mexican-American children following a weight management
      program.
AB  - OBJECTIVE: The objective was to evaluate quality of life (QOL) in at-risk-for
      overweight and overweight Mexican-American children after participating in 6
      months of intensive weight management or self-help. RESEARCH METHODS AND
      PROCEDURES: Eighty sixth- and seventh-grade at-risk-for-overweight (BMI >or=85th
      to <95th percentile) and overweight (BMI >or=95th percentile) Mexican-American
      children were randomly assigned to either intensive instructor-led intervention
      (ILI) or self-help (SH). The ILI condition included daily participation for 12
      weeks in a school-based program comprised of nutrition education, physical
      activity, and behavior modification, followed by ongoing monthly maintenance. QOL
      was assessed at baseline and 6 months via child self-report PedsQL. QOL outcomes
      were compared across treatment groups, and the impact of change in zBMI on change
      in QOL was evaluated. RESULTS: Children in the ILI condition not only achieved
      significantly greater weight loss (zBMI, -0.13 +/- 0.14; p < 0.001) but also
      significantly greater physical QOL improvements than those in the SH condition at
      6 months (p < 0.05). Furthermore, physical QOL increases were associated with
      zBMI reduction (p < 0.05). However, neither psychosocial nor total QOL was
      significantly impacted by intervention or zBMI change. DISCUSSION: These findings
      show that even modest decreases in zBMI after weight management result in
      improved physical QOL in Mexican-American children. These results illustrate the
      clear need to include evaluation of QOL in the process of identifying effective
      weight management programs.

PMID- 18070746
TI  - Association of major depression and binge eating disorder with weight loss in a
      clinical setting.
AB  - OBJECTIVE: Obesity has been linked to both major depressive disorder (MDD) and
      binge eating disorder (BED) in clinical and epidemiological studies. The present
      study compared weight loss among patients with and without MDD and BED who
      participated in a hospital-based weight loss program modeled after the Diabetes
      Prevention Program. RESEARCH METHODS AND PROCEDURES: Of 131 obese patients who
      enrolled in treatment, 17% were diagnosed with MDD only, 13% were diagnosed with
      BED only, 17% were diagnosed with both MDD and BED, and 53% lacked either
      diagnosis in a pretreatment clinical interview. RESULTS: After treatment,
      patients with MDD only attained 63% of the weight loss that non-depressed
      patients attained. Patients with BED only attained 55% of the weight loss that
      non-binge eaters attained. The effect of MDD on weight loss was not accounted for
      by the presence of BED or vice versa. Only 27% of patients with both MDD and BED
      achieved clinically significant weight loss compared with 67% of patients who had
      neither disorder. Results were not significantly altered when gender, age, and
      diabetes status were adjusted. CONCLUSION: Both MDD and BED were prevalent among
      this obese clinical population, and each disorder was independently associated
      with worse outcomes. Research is needed to investigate how to increase the
      efficacy of behavioral weight loss programs for individuals with MDD and/or BED.

PMID- 18070747
TI  - Induction of circadian gene expression in human subcutaneous adipose-derived stem
      cells.
AB  - OBJECTIVE: Genes encoding the circadian transcriptional apparatus exhibit robust
      oscillatory expression in murine adipose tissues. This study tests the hypothesis
      that human subcutaneous adipose-derived stem cells (ASCs) provide an in vitro
      model in which to monitor the activity of the core circadian transcriptional
      apparatus. RESEARCH METHODS AND PROCEDURES: Primary cultures of undifferentiated
      or adipocyte-differentiated ASCs were treated with dexamethasone, rosiglitazone,
      or 30% fetal bovine serum. The response of undifferentiated ASCs to dexamethasone
      was further evaluated in the presence of lithium chloride. Lithium inhibits
      glycogen synthase kinase 3, a key component of the circadian apparatus. Total RNA
      was harvested at 4-hour intervals over 48 hours and examined by real-time reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: Adipocyte
      differentiated cells responded more rapidly to treatments than their donor
      matched undifferentiated controls; however, the period of the circadian gene
      oscillation was longer in the adipocyte-differentiated cells. Dexamethasone
      generated circadian gene expression patterns with mean periods of 25.4 and 26.7
      hours in undifferentiated and adipocyte-differentiated ASCs, respectively. Both
      rosiglitazone and serum shock generated a significantly longer period in
      adipocyte-differentiated ASCs relative to undifferentiated ASCs. The Bmal1
      profile was phase-shifted by approximately 8 to 12 hours relative to Per1, Per3,
      and Cry2, consistent with their expression in vivo. Lithium chloride inhibited
      adipogenesis and significantly lengthened the period of Per3 and Rev-erbalpha
      gene expression profiles by >5 hours in dexamethasone-activated undifferentiated
      ASCs. DISCUSSION: These results support the initial hypothesis and validate ASCs
      as an in vitro model for the analysis of circadian biology in human adipose
      tissue.

PMID- 18070748
TI  - Inhibitory effect of (-)-epigallocatechin-3-gallate on lipid accumulation of 3T3
      L1 cells.
AB  - OBJECTIVE: The objective of this study was to investigate the molecular
      mechanisms underlying the attenuating effect of (-)-epigallocatechin-3-gallate
      (EGCG) on proliferation and lipid accumulation of 3T3-L1 cells, with a focus on
      the duration of EGCG treatment. RESEARCH METHODS AND PROCEDURES: Cell viability
      was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay and
      diamidino-2-phenylindole staining. The anti-adipogenic effect of EGCG on 3T3-L1
      cells was analyzed by glycerol-3-phosphate dehydrogenase activity and Oil red O
      staining. Western blot analysis was used to detect adenosine monophosphate
      activated protein kinase (AMPK) activation and phosphorylation of its substrate,
      acetyl-CoA carboxylase (ACC), and expression of insulin (INS) receptor, INS
      receptor substrate-1 (IRS-1), and adipocyte marker proteins. RESULTS: Exposure to
      EGCG during the early period of adipogenesis (7 days) was sufficient to prevent
      lipid accumulation. During this period, EGCG greatly decreased expression of the
      adipocyte marker proteins peroxisome proliferator-activated receptor gamma2
      (PPARgamma2) and liver X receptor (LXR)-alpha. Furthermore, EGCG significantly
      induced generation of reactive oxygen species (ROS), which led to AMPK
      activation, and these effects were eliminated by N-acetylcysteine (NAC)
      treatment. Also, EGCG increased the tyrosine phosphorylation of INS receptor and
      INS-1 with increasing incubation time. In contrast, EGCG treatment did not alter
      glycerol release in the presence or absence of 2',5'-dideoxyadenosine (DDA),
      indicating that EGCG had no effect on lipolysis. DISCUSSION: Our data demonstrate
      that EGCG decreased cell viability and inhibited differentiation of 3T3-L1 cells
      in a manner dependent on the duration of treatment. Also, we showed that
      inhibition of adipocyte differentiation by EGCG was associated with decreased
      glycerol-3-phosphate dehydrogenase (GPDH) activity accompanied by a strong
      inhibition of PPARgamma2-induced transcriptional activity. Furthermore, the
      inhibition of adipocyte differentiation by EGCG involved generation of ROS and
      activation of AMPK.

PMID- 18070749
TI  - Changes in gene expression in skeletal muscle in response to fat overfeeding in
      lean men.
AB  - OBJECTIVE: The adaptive mechanisms in response to excess energy supply are still
      poorly known in humans. Our aims were to define metabolic responses and changes
      in gene expression in skeletal muscle of healthy volunteers during fat
      overfeeding. RESEARCH METHODS AND PROCEDURES: Eight lean young healthy men were
      given a diet rich in saturated fat with an excess of approximately 550 kcal/d for
      4 weeks. Using oligonucleotide microarrays, gene expression changes in skeletal
      muscle were analyzed at Day 0, Day 14, and Day 28. RESULTS: Fat overfeeding led
      to an increase in body weight (1.0 +/- 0.3 kg) and waist circumference (2.2 +/-
      0.5 cm, p = 0.005) and a significant decrease in fasting non-esterified fatty
      acid plasma levels (-29 +/- 5%, p = 0.028). Respiratory quotient was
      significantly increased (0.84 +/- 0.01 to 0.88 +/- 0.02, p = 0.034) and lipid
      oxidation rate tended to decrease. The expression of 55 genes was modified in
      skeletal muscle. The main pathways indicated a coordinated stimulation of
      triacylglycerol synthesis, inhibition of lipolysis, reduction of fatty acid
      oxidation, and development of adipocytes. Promoter analysis of the regulated
      genes suggests that sterol regulatory element binding proteins might be important
      players of the short-term adaptation to fat overfeeding in human skeletal muscle.
      DISCUSSION: This combined metabolic and genomic investigation shows that fat
      overfeeding for 28 days promotes the storage of the excess energy in lean men and
      demonstrates the usefulness of a transcriptomic approach to a better
      understanding of the metabolic adaptation to changes in nutritional behavior in
      human.

PMID- 18070750
TI  - Adipocyte-derived lipoprotein lipase induces macrophage activation and monocyte
      adhesion: role of fatty acids.
AB  - OBJECTIVE: We evaluated the effect of adipocyte-derived lipoprotein lipase (LPL)
      on macrophage activation and monocyte adhesion and the role of fatty acids in
      these effects. RESEARCH METHODS AND PROCEDURES: 3T3-L1 adipocytes were incubated
      with heparin or insulin to induce LPL secretion; then adipocyte conditioned media
      (CM) were added to cultured J774 macrophages or human aortic endothelial cells
      (HAECs). Macrophage cytokine production and monocyte adhesion to HAECs were
      determined. RESULTS: Incubation of macrophages with heparin- or insulin-treated
      adipocyte CM increased tumor necrosis factor alpha, interleukin-6, and nitric
      oxide production by these cells. LPL neutralization and heparinase treatment
      prevented these effects. Addition of active LPL or palmitate to cultured
      macrophages replicated these effects. Blockade of leptin also reduced the effect
      of insulin-treated adipocyte CM on macrophage inflammatory changes. Induction of
      macrophage cytokine secretion by leptin was prevented by LPL
      immunoneutralization. Finally, addition of CM of heparin- or insulin-treated
      adipocytes to HAECs stimulated monocyte adhesion to these cells, an effect that
      was abrogated by an anti-LPL antibody. This effect was reproduced by treating
      HAECs with active LPL or palmitate. DISCUSSION: These results point to an effect
      of LPL-mediated lipolysis in macrophage activation and monocyte adhesion.

PMID- 18070751
TI  - Effects of dietary lactose on long-term high-fat-diet-induced obesity in rats.
AB  - OBJECTIVE: In this study, we examined the effects of lactose on long-term high
      fat-diet-induced obesity in rats. RESEARCH METHODS AND PROCEDURES: A total of 112
      Sprague-Dawley strain female rats (6 weeks old) were divided into four groups: a
      basic control diet group (Cont), 10% lactose diet group (Lac), high-fat diet
      group (Fat), and high-fat with 10% lactose diet group (Fat+Lac). After 0, 7, 14,
      and 84 days from starting the experimental diet, the animals were fasted
      overnight and killed by bleeding from the abdominal aorta under anesthesia (n = 8
      or 9/group). RESULTS: After 84 days, the addition of lactose to the high-fat diet
      decreased the final body weight, body weight gain, fat accumulation, and the
      levels of serum leptin, serum triglycerides, and serum glucose significantly (p <
      0.05). Although there was no significant difference in the levels of serum
      calcium and phosphorus between the Fat and Fat+Lac groups, lumbar vertebral bone
      mineral density was significantly higher in the Fat+Lac group than in the Cont
      group on Day 82. Interestingly, the level of serum 1alpha, 25-dihydroxyvitamin
      D(3) in the Fat+Lac group on Day 84 was reduced by 74% compared with the Fat
      group (p < 0.01), while there was no significant difference in serum parathyroid
      hormone levels between the Fat and Fat+Lac groups. DISCUSSION: This is the first
      study to suggest that the addition of lactose to a long-term high-fat diet may
      regulate not only calcium metabolism but also fat deposition. Further studies on
      the mechanism of dietary lactose in the regulation of adiposity would provide
      valuable data for the prevention of long-term high-fat-diet-induced obesity.

PMID- 18070752
TI  - Ghrelin enhances in vivo skeletal muscle but not liver AKT signaling in rats.
AB  - OBJECTIVE: Ghrelin administration can induce fat weight gain and hyperglycemia
      (potentially through ghrelin-induced hepatic glucose production), but plasma
      ghrelin is positively associated with whole-body insulin sensitivity (mainly
      reflecting muscle insulin action) being increased in lean individuals or after
      diet-induced weight loss and reduced in obesity or after diet-induced weight
      gain. To investigate potential mechanisms, we measured in vivo effects of
      sustained ghrelin administration at a non-orexigenic dose on skeletal muscle and
      liver insulin signaling at the AKT level and adipokine expression changes.
      RESEARCH METHODS AND PROCEDURES: Young-adult male rats received 4-day, twice
      daily subcutaneous ghrelin (200 mug/injection) or saline. We measured skeletal
      muscle (mixed, gastrocnemius; oxidative, soleus) and liver protein levels of
      activated [phosphorylated (P)] and total (T) AKT and glycogen synthase kinase
      (GSK; reflecting AKT-dependent GSK inactivation) and epididymal adipose tissue
      adipokine mRNA. RESULTS: Ghrelin increased body weight (+1.4%) and blood glucose
      (both p < 0.05 vs. saline) but not food intake, plasma insulin, or free fatty
      acids. Ghrelin, however, enhanced P/T/AKT and P/T/GSK ratios and glucose
      transporter-4 mRNA in soleus (p < 0.05), but not in gastrocnemius, muscle. In
      contrast, ghrelin reduced hepatic P/T-AKT and P/T-GSK. No alterations occurred in
      adiponectin, leptin, or resistin transcripts or plasma adiponectin. DISCUSSION:
      Despite moderate weight gain and in the absence of insulin-free fatty acid
      changes, sustained ghrelin administration enhanced oxidative muscle AKT
      activation. Reduced liver AKT signaling could potentially contribute to
      concomitant blood glucose increments. These findings support ghrelin as a novel
      tissue-specific modulator of lean tissue AKT signaling with insulin-sensitizing
      effects in skeletal muscle but not in liver in vivo.

PMID- 18070753
TI  - Effects of subcutaneous leptin injections on hypothalamic gene profiles in lean
      and ob/ob mice.
AB  - OBJECTIVE: Leptin-deficient ob/ob mice are more sensitive to exogenous leptin
      than lean mice and leptin treatment normalizes many of the phenotypic
      characteristics of ob/ob mice. The primary objective of this experiment was to
      investigate whether this altered leptin sensitivity in ob/ob mice was reflected
      in the hypothalamic mRNA profile. RESEARCH METHODS AND PROCEDURES: Fifteen-week
      old female ob/ob and lean mice were treated with 14 days of subcutaneous (sc)
      infusion of phosphate-buffered saline (PBS) or leptin (10 mug/d) using osmotic
      pumps. Real-time Taqman reverse transcription polymerase chain reaction (RT-PCR)
      (ABI Microfluidic cards) was used to quantitatively compare the mRNA levels of
      selected hypothalamic genes in these groups. RESULTS: Hypothalamic mRNA levels
      for ob/ob control mice were higher for agouti-related protein (AGRP),
      neuropeptide Y (NPY), and arginine vasopressin (AVP), and lower for cocaine- and
      amphetamine-regulated transcript (CART), cAMP response element binding protein
      (CREB)-1, proopiomelanocortin (POMC)-1, and urocortin (UCN)-3 compared with lean
      controls. In leptin-treated ob/ob mice, hypothalamic mRNA levels were reduced for
      NPY, AGRP, AVP, and increased for suppressor of cytokine signaling 3 (SOCS3)
      compared with ob/ob controls. Leptin treatment dramatically up-regulated
      hypothalamic mRNA level of POMC1 in both lean and ob/ob mice. Strong correlations
      were observed between hypothalamic Janus kinase 2 (JAK2) and CREB1, STAT3 and
      CREB1, JAK2 and STAT3, NPY and AVP in all samples. DISCUSSION: ob/ob and lean
      mice have different hypothalamic mRNA expression patterns (particularly those of
      feeding-related genes), and selected genes in ob/ob mice are more sensitive to
      exogenous leptin stimulation compared with lean mice.

PMID- 18070754
TI  - More activated cardiac mitochondrial-dependent apoptotic pathway in obese Zucker
      rats.
AB  - BACKGROUND: Obesity is often associated with the development of heart failure,
      but the precise mechanisms remain uncertain. The purpose of this study was to
      evaluate the key components of the mitochondrial-dependent apoptotic pathway in
      excised heart from obese Zucker rats. METHODS: Twelve obese Zucker rats were
      studied at 5 to 6 months of age, and 12 age-matched lean Zucker rats served as
      control. The myocardial architecture and key components of the mitochondrial
      dependent apoptotic pathway in the excised left ventricle from rats were measured
      by histopathological analysis, Western blotting, and reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: The ratios of whole heart weight to
      tibia length were significantly increased in the obese group. Cardiomyocyte
      disarray, the increased interstitial space, and minor cardiac fibrosis were
      observed in obese rat hearts. Pro-apoptotic Bcl2 family members, Bcl-2/adenovirus
      E1B 19 kDa interacting protein (BNIP3) and Bad levels, were significantly
      increased in obese rat hearts, whereas anti-apoptotic Bcl2 family member, Bcl2
      level, was significantly decreased. Cytosolic cytochrome c indicating cytochrome
      c release from mitochondria was significantly increased in obese rat heart. In
      addition, upstream pro-caspase-9 and pro-caspase-3 were significantly decreased,
      whereas activated caspase-9 and activated caspase-3 were significantly increased
      in obese rat hearts, compared with lean rat heart, implying that pro-forms of
      caspase-9 and caspase-3 were cleaved into active-forms caspase-9 and caspase-3.
      CONCLUSIONS: The cardiac mitochondrial-dependent apoptotic pathway was more
      activated in obese Zucker rats than in lean rats, which may provide one possible
      apoptotic mechanism for developing heart failure in obesity.

PMID- 18070755
TI  - Preproghrelin-derived peptide, obestatin, fails to influence food intake in lean
      or obese rodents.
AB  - OBJECTIVES: Obestatin has been initially characterized as a new peptide derived
      from the ghrelin precursor, which suppresses food intake and inhibits the
      orexigenic and prokinetic actions of ghrelin when injected peripherally or
      centrally in lean mice. However, reproducing these data remains controversial.
      Reasons for the disparity may be the use of different doses, routes, and animal
      models. We aimed to investigate the effects of peripheral and intracisternal (IC)
      injection of obestatin on feeding, gastric motility, and blood glucose in rats as
      well as in diet-induced obese (DIO) mice. RESEARCH METHODS AND PROCEDURES: Food
      intake and gastric emptying of a semi-liquid caloric meal were measured after
      intraperitoneal (IP) injection of obestatin in rats and DIO mice. Gastric phasic
      motility and blood glucose were monitored in urethane-anesthetized rats after IC
      or intravenous (IV) injection of obestatin. RESULTS: Obestatin injected
      intraperitoneally at doses ranging from 0.1 to 3 mg/kg influenced neither acute
      food intake nor gastric emptying in rats. Obestatin injected intravenously at 0.3
      or 3 mg/kg and IC at 7.5 or 30 microg/rat modified neither fasted gastric phasic
      motility nor blood glucose levels, while ghrelin (30 microg/kg, IV) increased and
      vagotomy suppressed gastric motility, and an oligosomatostatin analog (3
      microg/rat, IC) decreased blood glucose. Obestatin, injected intraperitoneally
      (0.3 mg/kg) in DIO mice, did not alter feeding response to a fast, while
      urocortin 1 (10 microg/kg, IP) induced a 73.3% inhibition at 2 hours. DISCUSSION:
      Our data demonstrate that peripheral administration of obestatin did not modify
      food intake in rats or obese mice or gastric motor function in rats.

PMID- 18070756
TI  - Prolonged decrease of adipocyte size after rosiglitazone treatment in high- and
      low-fat-fed rats.
AB  - OBJECTIVE: The anti-diabetic thiazolidinediones (TZDs) stimulate adipocyte
      differentiation and decrease mean adipocyte size. However, whether these smaller,
      more insulin-sensitive adipocytes maintain their size after TZD therapy is
      discontinued has not been studied. RESEARCH METHODS AND PROCEDURES: Adult female
      Sprague-Dawley rats were fed a low-fat (10% fat) diet or, to elevate body weight
      (BW), a high-fat (HF) diet (45% fat) for 6 weeks. Rats were initially randomized
      to groups (n = 12) fed either low-fat or HF diets, with or without the TZD
      rosiglitazone (ROSI; 5 mg/kg per day), for 6 weeks. ROSI was then discontinued,
      and all animals were fed HF for another 6 weeks before sacrifice. Retroperitoneal
      (RP) adipose tissue morphology was determined from tissue collected by serial
      biopsies before and after 6 weeks of ROSI treatment and at sacrifice. RESULTS:
      Measures of BW and adiposity did not differ among groups 6 weeks after stopping
      ROSI treatment. However, during treatment, ROSI in both diets significantly
      decreased RP adipocyte size and increased RP DNA content, and these effects
      continued to be observed after discontinuing treatment. ROSI administration also
      decreased circulating insulin, leptin, and triglycerides and increased
      circulating adiponectin levels; however, these effects were reversed on stopping
      treatment. DISCUSSION: These results demonstrated that TZD-induced effects on
      adipocyte size and number were maintained after discontinuing treatment, even
      with consumption of an obesigenic diet. However, additional studies are needed to
      determine whether TZD-treated animals eventually achieve an adipocyte size
      similar to that of untreated animals at the expense of a higher BW.

PMID- 18070757
TI  - Role of adiponectin and inflammation in insulin resistance of Mc3r and Mc4r
      knockout mice.
AB  - OBJECTIVE: To investigate the involvement of hypoadiponectinemia and inflammation
      in coupling obesity to insulin resistance in melanocortin-3 receptor and
      melanocortin-4 receptor knockout (KO) mice (Mc3/4rKO). RESEARCH METHODS AND
      PROCEDURES: Sera and tissue were collected from 6-month-old Mc3rKO, Mc4rKO, and
      wild-type C57BL6J litter mates maintained on low-fat diet or exposed to high-fat
      diet (HFD) for 1 or 3 months. Inflammation was assessed by both real-time
      polymerase chain reaction analysis of macrophage-specific gene expression and
      immunohistochemistry. RESULTS: Mc4rKO exhibited hypoadiponectinemia, exacerbated
      by HFD and obesity, previously reported in murine models of obesity. Mc4r
      deficiency was also associated with high levels of macrophage infiltration of
      adipose tissue, again exacerbated by HFD. In contrast, Mc3rKO exhibited normal
      serum adiponectin levels, irrespective of diet or obesity, and a delayed
      inflammatory response to HFD relative to Mc4rKO. DISCUSSION: Our findings suggest
      that severe insulin resistance of Mc4rKO fed a HFD, as reported in other models
      of obesity such as leptin-deficient (Lep(ob)/Lep(ob)) and KK-A(y) mice, is linked
      to reduced serum adiponectin and high levels of inflammation in adipose tissue.
      Conversely, maintenance of normal serum adiponectin may be a factor in the
      relatively mild insulin-resistant phenotype of severely obese Mc3rKO. Mc3rKO are,
      thus, a unique mouse model where obesity is not associated with reduced serum
      adiponectin levels. A delay in macrophage infiltration of adipose tissue of
      Mc3rKO during exposure to HFD may also be a factor contributing to the mild
      insulin resistance in this model.

PMID- 18070758
TI  - An exploratory study of cardiac function and oxygen uptake during cycle ergometry
      in overweight children.
AB  - OBJECTIVE: Obesity has been proposed to negatively impact cardiac function in
      overweight (OW) individuals. The relationship between diastolic dysfunction and
      oxygen uptake (Vo(2)) kinetics is equivocal. This exploratory investigation
      evaluated the relationship between resting left ventricular function and Vo(2)
      kinetics during cycle ergometry in OW and non-overweight (NO) children and
      adolescents. RESEARCH METHODS AND PROCEDURES: Fourteen OW (>85 percentile for BMI
      for age and gender) children, 10 boys and 4 girls (age, 11.7 +/- 1.9 years; body
      mass, 80.6 +/- 45.5 kg) and 10 NO children (4 boys, 6 girls) volunteered to
      participate in the study (age, 12.5 +/- 2.1 years; body mass, 45.8 +/- 13.8 kg).
      Resting cardiovascular structure and function were assessed using spectral
      Doppler echocardiography. All subjects underwent two sub-maximal exercise stages
      on a cycle ergometer (3 minutes unloaded and 5 minutes at 50 W, both at a cadence
      of 50 rpm). Respiratory data were measured on a breath-by-breath basis at both
      workloads and the mean response time (MRT) was calculated. RESULTS: Analysis of
      the MRT data demonstrated that there were no significant differences between OW
      and NO (OW, 52.6 +/- 11.7 seconds vs. NO, 45.6 +/- 7.4 seconds). Significant
      correlations (p < 0.05) were obtained between MRT Vo(2) and echocardiographic
      derived mitral valve inflow pressure half-time (r = 0.55) and between MRT Vo(2),
      and mitral valve inflow deceleration time (r = 0.55). DISCUSSION: The evidence
      from this research suggests a possible link between left ventricular diastolic
      function at rest and oxygen uptake kinetics during sub-maximal exercise in OW and
      NO children and adolescents.

PMID- 18070759
TI  - Basal metabolic rate and autonomic nervous system dysfunction in men with spinal
      cord injury.
AB  - OBJECTIVES: The purpose of this study was to determine the relationship between
      autonomic nervous system dysfunction and basal metabolic rate (BMR), and the
      effect of spasticity on basal metabolic rate. RESEARCH METHOD AND PROCEDURES:
      Twenty men (11 paraplegic and 9 tetraplegic) with American Spinal Injury
      Association (ASIA)-A and -B grade chronic spinal cord injury (SCI) participated
      in this study. Total body fat mass and lean tissue mass were measured in all
      participants using DXA by standard methods. Patients were allocated into 2 groups
      to determine the effect of autonomic nervous system dysfunction on BMR: Group I
      (T6 and upper-level injuries with history of autonomic dysreflexia) and Group II
      (T7 and lower-level injuries without history of autonomic dysreflexia).
      Measurements of BMR were determined by indirect calorimetry under standardized
      conditions. RESULTS: There were 13 patients in Group I and 7 patients in Group II
      and the difference between these two in terms of time since injury, BMI, age,
      weight, lean tissue mass, BMR, and BMR/kg were not significant. CONCLUSION: We
      concluded that autonomic nervous system dysfunction does not affect BMR, and it
      might be ignored in considering energy needs in spinal cord injury.

PMID- 18070760
TI  - Regional body volumes, BMI, waist circumference, and percentage fat in severely
      obese adults.
AB  - OBJECTIVE: This study presents total body volume (TBV) and regional body volume,
      and their relationships with widely used body composition indices [BMI, waist
      circumference (WC), and percentage body fat (% fat)] in severely obese adults
      (BMI >or=35 kg/m(2)). RESEARCH METHODS AND PROCEDURES: We measured TBV, trunk
      volume (TV), arm volume (AV), leg volume (LV), and WC and estimated % fat in 32
      severely obese persons with BMI 36 to 62 kg/m(2) (23 women; age, 19 to 65 years;
      weight, 91 to 182 kg) and in 58 persons with BMI <35 kg/m(2) (28 women; age, 18
      to 83 years; weight, 48 to 102 kg) using a newly validated 3-day photonic image
      scanner (3DPS, Model C9036-02, Hamamatsu Co., Japan) and calculated TV/TBV,
      AV/TBV, and LV/TBV. RESULTS: Men had significantly larger TBV and higher TV/TBV
      and AV/TBV, but significantly lower LV/TBV than women, independently of BMI.
      TV/TBV increased while AV/TBV and LV/TBV decreased with increasing BMI, WC, and %
      fat, and the rate of increase in TV/TBV per % fat was significantly greater in
      severely obese individuals than in individuals with BMI <35 kg/m(2). The
      relationships for TBV with % fat were much lower than with BMI or WC. CONCLUSION:
      Body volume gains were mainly in the trunk region in adults, irrespective of sex
      or BMI. For a given BMI, WC, or % fat, men had a significantly larger TV than
      women. The implication is that men could have higher health risks due to having
      higher trunk body weight as a proportion of total body weight compared with
      severely obese or less severely obese women.

PMID- 18070761
TI  - Chromium (D-phenylalanine)3 improves obesity-induced cardiac contractile defect
      in ob/ob mice.
AB  - OBJECTIVE: Low-molecular weight chromium compounds, such as chromium picolinate
      [Cr(pic)(3)], improve insulin sensitivity, although toxicity is a concern. We
      synthesized a novel chromium complex, chromium (d-phenylalanine)(3) [Cr(d
      phe)(3)], in an attempt to improve insulin sensitivity with reduced toxicity. The
      aim of this study was to compare the two chromium compounds on cardiac
      contractile function in ob/ob obese mice. RESEARCH METHODS AND PROCEDURES: C57BL
      lean and ob/ob obese mice were randomly divided into three groups: H(2)O, Cr(d
      phe)(3), or Cr(pic)(3) (45 mug/kg per day orally for 6 months). RESULTS: The
      glucose tolerance test displayed improved glucose clearance by Cr(d-phe)(3) but
      not Cr(pic)(3). Myocytes from ob/ob mice exhibited depressed peak shortening (PS)
      and maximal velocity of shortening/relengthening (+/-dL/dt), prolonged time-to-PS
      and time-to-90% relengthening (TR90), reduced electrically stimulated rise in
      intracellular Ca(2+) (Deltafura-2 fluorescence intensity), and slowed
      intracellular Ca(2+) decay. Although a 3-month Cr(d-phe)(3) treatment for a
      separate group of ob/ob and lean 2-month-old mice only rectified reduced +/-dL/dt
      in ob/ob mice, all mechanical and intracellular Ca(2+) abnormalities were
      significantly attenuated or ablated by 6 months of Cr(d-phe)(3) but not
      Cr(pic)(3) treatment (except TR90). Sarco(endo)plasmic reticulum Ca(2+) ATPase
      activity and Na(+)-Ca(2+) exchanger expression were depressed in ob/ob mice,
      which were reversed by both Cr(d-phe)(3) and Cr(pic)(3), with a more pronounced
      effect from Cr(d-phe)(3). Cr(d-phe)(3) corrected reduced insulin-stimulated
      glucose uptake and improved basal phosphorylation of Akt and insulin receptor, as
      well as insulin-stimulated phosphorylation of Akt and insulin receptor in ob/ob
      myocytes. Heart homogenates from ob/ob mice had enhanced oxidative stress and
      protein carbonyl formation compared with the lean group, which were attenuated by
      both Cr(d-phe)(3) and Cr(pic)(3). DISCUSSION: Our data suggest that the new Cr(d
      phe)(3) compound possesses better cardio-protective and insulin-sensitizing
      properties against obesity.

PMID- 18070762
TI  - The safety profiles of orlistat and sibutramine: results of prescription-event
      monitoring studies in England.
AB  - INTRODUCTION: Observational cohort studies were conducted using prescription
      event monitoring (PEM) to examine the safety profiles of the anti-obesity agents
      orlistat and sibutramine. Adverse events reported as case reports were also
      evaluated to determine whether these events were also identified by PEM. RESEARCH
      METHODS AND PROCEDURES: Patients were identified from dispensed prescriptions
      written by general practitioners (GPs) in England for orlistat or sibutramine.
      Patient demographic and clinical event information, including reasons for
      stopping and adverse drug reactions, were requested on questionnaires posted to
      GPs at least 6 months after the first prescription for individual patients. Event
      incidence densities (IDs) (number of first reports of event/1000 patient-months
      treatment) were calculated for month 1 (ID(1)) and months 2-3 (ID(2-3)).
      Published case reports were identified by searching Medline and Embase. RESULTS:
      The cohorts comprised 16,021 and 12,336 patients prescribed orlistat and
      sibutramine, respectively. Both cohorts had a median age of 45 years, and
      approximately 80% were female. The most common reason for stopping orlistat
      within 3 months was diarrhea (332 patients; 2.1% cohort), and for stopping
      sibutramine it was hypertension (203 patients; 1.6%). Clinical events
      significantly associated with taking orlistat were mainly gastrointestinal and
      those for sibutramine included central nervous system effects, nausea/vomiting,
      palpitation, and sweating. We identified 8 published case reports for orlistat
      and 10 for sibutramine that had equivalent or similar events assessed as causally
      related in the PEM studies. CONCLUSIONS: The PEM studies highlighted different
      adverse event profiles for orlistat and sibutramine that were consistent with
      their distinct pharmacological mechanisms and other published information.

PMID- 18070763
TI  - Association of lipin 1 gene polymorphisms with measures of energy and glucose
      metabolism.
AB  - OBJECTIVE: To examine the importance of lipin 1 (LPIN1) gene variation in energy
      and glucose metabolism. Transgenic animal models have shown that lipin, a protein
      encoded by the LPIN1 gene, promotes fat synthesis and storage in adipose tissue
      while decreasing energy expenditure and lipid oxidation in skeletal muscle. Lpin1
      was identified as the mutated gene in the fatty liver dystrophy mouse, which
      exhibits lipin deficiency and features of human lipodystrophy. RESEARCH METHODS
      AND PROCEDURES: We genotyped five LPIN1 polymorphisms and tested for association
      with resting metabolic rate (RMR), fat oxidation, fasting plasma insulin and
      glucose concentration, and obesity-related phenotypes, including BMI, body fat
      percentage, sum of six skinfolds, and waist circumference in 712 subjects of the
      Quebec Family Study. RESULTS: The strongest results were generation-specific. In
      parents, RMR of the G/G IVS13 + 3333A>G homozygotes was 107 kcal/d higher than in
      A/A homozygotes and 39 kcal/d higher than in A/G heterozygotes (p = 0.0003). In
      offspring, carriers of the C allele of the IVS18 + 181C>T variant had
      significantly higher (p < 0.0003) insulin levels than T/T homozygotes. These
      associations remained significant after adjusting for multiple testing. Several
      other associations between body composition measures and the IVS18 + 181C>T
      variant were significant (p = 0.05 to 0.003), suggesting a strong pattern of
      relationships. DISCUSSION: These findings support the hypothesis that sequence
      variation in the LPIN1 gene contributes to variation in RMR and obesity-related
      phenotypes potentially in an age-dependent manner.

PMID- 18070765
TI  - Shifts in patterns and consumption of beverages between 1965 and 2002.
AB  - BACKGROUND: Beverage patterning may play a role in partially explaining the
      rising rates of obesity in the United States, yet little work on overall trends
      and patterns exits. Our objective was to examine trends and patterns of beverage
      consumption among U.S. adults. METHODS: We used data from the nationally
      representative Nationwide Food Consumption Surveys (1965, 1977 to 1978) and the
      National Health and Nutrition Surveys (1988 to 1994, 1999 to 2002). To examine
      trends we determined percent consuming and per capita and per consumer caloric
      intake from all beverages. We used cluster analysis to determine year-specific
      beverage patterns in 1977 and 2002. RESULTS: The percentage of calories from
      beverages significantly increased between 1965 (11.8%), 1977 (14.2%), 1988
      (18.5%), and 2002 (21.0%); this represents an overall increase of 222 calories
      per person per day from beverages, resulting largely from increased intake of
      calorically sweetened beverages. Beverage patterns in 2002 were more complex than
      in 1977 and were dominated by a greater number of beverages, reflecting the
      increase in alcohol, soda, and diet beverages. CONCLUSION: Calories from
      beverages increased substantially from 1965 to 2002, providing a considerable
      source of daily calories. Given the upward trends in calorically sweetened,
      nutrient-deficient beverages and the shifts in overall beverage patterns,
      addressing beverage intake is a salient issue for adults.

PMID- 18070764
TI  - Effects of a reimbursement incentive on enrollment in a weight control program.
AB  - OBJECTIVE: The objective was to examine the effect of offering a reimbursement
      incentive on the percentage of inquirers who enrolled in a weight control program
      and on weight loss and program attendance among enrollees. RESEARCH METHODS AND
      PROCEDURES: We used a sequential control-intervention design to observe how
      inquirers of the University of Alabama at Birmingham EatRight Lifestyle Program
      responded to an enrollment incentive for potential 50% ($150) reimbursement of
      the total program fee if they attended 10 of 12 classes and lost at least 6% of
      their current body weight. Inquirers had to be adults with a BMI >or=30 kg/m(2),
      seeking information about a weight control program, and informed of the program
      cost. Outcomes included proportion of inquirers enrolled, overall number of
      classes attended, and weight loss. RESULTS: Of the 401 people who inquired during
      the study periods, 24.5% and 25.0% enrolled in the intervention and control
      periods, respectively. There was a trend toward higher attendance in the
      intervention group, compared with the control group; there were no differences in
      percentage of weight loss. The odds of attending >or=10 classes were 2.4 times as
      high, and both losing >6% body weight and attending >or=10 classes were three
      times as high in the intervention subjects compared with controls, although non
      significant. DISCUSSION: The potential of earning a performance-based
      reimbursement incentive did not affect enrollment in the EatRight Lifestyle
      Program. Performance-based incentives may be an ideal mechanism for extending
      coverage of weight-loss interventions by insurers because of limited financial
      risk and improved adherence.

PMID- 18070766
TI  - Personal, behavioral, and environmental risk and protective factors for
      adolescent overweight.
AB  - OBJECTIVE: The objective was to examine a breadth of personal, behavioral, and
      socio-environmental factors as potential risk and protective factors of
      overweight among male and female adolescents. RESEARCH METHODS AND PROCEDURES: A
      longitudinal study was conducted with an ethnically and socio-economically
      diverse sample of 2516 adolescents who completed surveys at both Time 1 (1998 to
      1999) and Time 2 (2003 to 2004) of the Project Eating Among Teens (EAT) study.
      RESULTS: In 1998 to 1999, 335 (25.7%) girls and 282 (26.4%) boys met the age
      adjusted criteria for overweight. During the 5-year study period, 236 (70.5%) of
      the overweight girls and 185 (65.7%) of the overweight boys remained overweight
      and 115 (12.0%) girls and 77 (9.9%) boys originally not overweight became
      overweight. Although differences by sex were found, a number of personal,
      behavioral, and socio-environmental factors were associated with overweight among
      both male and female adolescents. Body dissatisfaction and weight concerns at
      Time 1 predicted overweight at Time 2 for both male and female adolescents.
      Dieting and use of unhealthy weight control behaviors at Time 1 also predicted
      overweight at Time 2. Greater frequency of breakfast consumption at Time 1 was
      protective against overweight. Higher levels of weight-related teasing and
      parental weight-related concerns and behaviors at Time 1 were positively
      associated with Time 2 overweight. DISCUSSION: Body dissatisfaction, weight
      concerns, use of unhealthy weight control behaviors, weight-related
      stigmatization, and parental concern about the child's weight may increase risk
      for adolescent overweight. Interventions that enhance adolescents' body
      satisfaction while providing them with skills to avoid dieting and to engage in
      more effective weight-control behaviors should be developed and tested.

PMID- 18070767
TI  - Accuracy of self-reported weight among bariatric surgery candidates: the
      influence of race and weight cycling.
AB  - OBJECTIVE: Research on the accuracy of self-reported weight has indicated that
      the degree of misreporting (underestimating) weight is associated with increasing
      weight but is variable across patient groups. We examined the degree of
      discrepancy between actual and self-reported BMI in severely obese bariatric
      surgery candidates, and whether the degree of accuracy varied by race and by
      eating-related and psychological factors. RESEARCH METHODS AND PROCEDURES:
      Participants were 179 obese female gastric bypass surgery candidates (31 black,
      22 Hispanic, 126 white) who were asked to self-report height and weight as part
      of a larger assessment battery. Actual height and weight were then measured and a
      discrepancy score was generated (actual BMI - reported BMI). RESULTS: In this
      group of severely obese patients, degree of misreporting was unrelated to BMI.
      The race groups did not differ in actual or self-reported BMI but differed
      significantly in the degree of misestimation between self-reported and actual
      BMI. Post hoc tests indicated that black women underestimated their BMI
      significantly more than white women; Hispanic women did not differ from the other
      race groups. No eating-related or psychological variables assessed predicted
      percentage discrepancy; however, the accuracy in self-reported weight was related
      to history of weight cycling. DISCUSSION: Overall, obese bariatric surgery
      candidates were accurate in self-report of weight, although the degree of
      accuracy differed by race and weight cycling history.

PMID- 18070768
TI  - Obesity and impairment in psychosocial functioning in women: the mediating role
      of eating disorder features.
AB  - OBJECTIVE: The objective was to test the hypothesis that, in women, the
      association between obesity and impairment in psychosocial functioning is
      mediated by levels of weight and shape concerns and/or binge-eating frequency.
      RESEARCH METHODS AND PROCEDURES: Self-report measures of eating disorder
      psychopathology, mental health functioning, subjective quality of life in the
      psychological and social domains, and days "out-of-role" associated with any
      (physical or mental) health problem, were completed by a community sample of
      women classified as obese (BMI >or=30 kg/m(2), n = 639) or non-obese (BMI <30
      kg/m(2), n = 4253). For each of the dependent measures, regression models were
      used to test the hypothesis of mediation by comparing the strength of the
      relationship between independent and dependent variables with and without
      inclusion of the putative mediator in the regression model. RESULTS: On each
      measure, the conditions for perfect mediation were satisfied when weight or shape
      concerns acted as the putative mediator, indicating that there was no association
      between obesity and functional impairment after controlling for weight or shape
      concerns. In contrast, associations between obesity and impairment in
      psychosocial functioning remained highly significant when binge-eating frequency
      was the putative mediator. DISCUSSION: The findings suggest that in women, weight
      and shape concerns are an important mediator of the relationship between obesity
      and impairment in psychosocial functioning, whereas binge eating may not be of
      primary importance. A greater focus on body acceptance in obesity treatment may
      be indicated.

PMID- 18070769
TI  - The evaluation of a mass media campaign aimed at weight gain prevention among
      young Dutch adults.
AB  - OBJECTIVE: The objective was to evaluate a 3-year nationwide mass media campaign
      aimed at preventing weight gain. The campaign was aimed primarily at raising
      awareness of the importance of weight-gain prevention and bringing these issues
      to the attention of the Dutch public. RESEARCH METHODS AND PROCEDURES: Eleven
      serial, independent, cross-sectional, population-based telephone surveys were
      used to assess campaign awareness and impact (N ranged between 483 and 493 for
      each of the 11 surveys). The surveys were conducted before and after six campaign
      waves. Multiple linear and logistic regression analyses were used to test for
      trends over time and for differences among the surveys for campaign awareness,
      message recall, perceived body weight status, overweight-related risk
      perceptions, attitudes, perceived social support, self-efficacy expectations, and
      motivations for preventing weight gain. RESULTS: Campaign awareness ranged from
      61% after the 1st campaign wave to 88.4% after the final wave. The campaign's
      television broadcasting activities were an important source of campaign
      awareness, from both the campaign's television commercials and television-based
      free publicity. Message recall ranged from 41.9% to 68.1%. Small positive
      differences were found in attitudes, perceived social support, and intentions for
      preventing weight gain. Additionally, the results suggest mixed effects on self
      efficacy expectations and a negative effect on risk perception. DISCUSSION: The
      campaign resulted in high campaign awareness, especially as a result of
      television commercials and free publicity on television. The results suggest that
      the campaign was able to create more positive attitudes and motivation but lower
      risk perceptions and efficacy for preventing weight gain.

PMID- 18070770
TI  - Maternal obesity is associated with younger age at obesity onset in U.S.
      adolescent offspring followed into adulthood.
AB  - OBJECTIVE: The objective was to test the hypothesis that maternal obesity is
      associated with younger age of offspring's obesity onset. RESEARCH METHODS AND
      PROCEDURES: We used prospective, nationally representative, longitudinal data
      collected across Waves I (1995; 12 to 20 years), II (1996; 13 to 20 years), and
      III (2001; 18 to 28 years) of the National Longitudinal Study of Adolescent
      Health (N = 14,654; 49% female). Interval regression analysis was used to assess
      the association between maternal obesity and age at offspring's obesity onset
      (International Obesity Task Force BMI >or=30 equivalent age- and sex-specific cut
      off points for adolescents and BMI >or=30 for young adults) using self-reported
      heights and weights, adjusting for race/ethnicity, sex, parental education, and
      family income, accounting for complex sampling design. RESULTS: The net effect of
      having an obese mother varied by race/ethnicity and was associated with a
      significantly earlier age at obesity onset (p = 0.0001) for whites [beta= -8.1
      year, 95% confidence interval (CI), -9.3; -6.9)], blacks (beta = -10.8 years, 95%
      CI, -12.4; -9.2), Hispanics (beta = -7.0 years, 95% CI, -9.2; -4.8), and Asians
      (beta = -8.6 years, 95% CI, -13.3; -3.9). Earlier obesity onset (<18 years) was
      associated with increased severity at young adulthood (mean BMI, 36.0 +/- 0.3
      kg/m(2)) vs. onset after age 18 (mean BMI, 34.4 +/- 0.2 kg/m(2); p = 0.0001).
      There were no sex differences in the association of maternal obesity to age at
      obesity onset. CONCLUSIONS: Having an obese mother was associated with earlier
      age at obesity onset across all race/ethnic groups, particularly non-Hispanic
      blacks. Early obesity onset has important health consequences because of its
      association with more severe adult obesity.

PMID- 18070771
TI  - First nationwide survey of prevalence of overweight, underweight, and abdominal
      obesity in Iranian adults.
AB  - OBJECTIVE: The goal was to estimate the prevalence of overweight, obesity,
      underweight, and abdominal obesity among the adult population of Iran. RESEARCH
      METHODS AND PROCEDURES: A nationwide cross-sectional survey was conducted from
      December 2004 to February 2005. The selection was conducted by stratified
      probability cluster sampling through household family members in Iran. Weight,
      height, and waist circumference (WC) of 89,404 men and women 15 to 65 years of
      age (mean, 39.2 years) were measured. The criteria for underweight, normal
      weight, overweight, and Class I, II, and III obesity were BMI <18.5, 18.5 to
      24.9, 25 to 29.9, 30 to 34.9, 35 to 39.9, and >or=40 (kg/m(2)), respectively.
      Abdominal obesity was defined as WC >or=102 cm in men and >or=88 cm in women.
      RESULTS: The age-adjusted means for BMI and WC were 24.6 kg/m(2) in men and 26.5
      kg/m(2) in women and 86.6 cm in men and 89.6 cm in women, respectively. The age
      adjusted prevalence of overweight or obesity (BMI >or=25) was 42.8% in men and
      57.0% in women; 11.1% of men and 25.2% of women were obese (BMI >or=30), while
      6.3% of men and 5.2% of women were underweight. Age, low physical activity, low
      educational attainment, marriage, and residence in urban areas were strongly
      associated with obesity. Abdominal obesity was more common among women than men
      (54.5% vs. 12.9%) and greater with older age. DISCUSSION: Excess body weight
      appears to be common in Iran. More women than men present with overweight and
      abdominal obesity. Prevention and treatment strategies are urgently needed to
      address the health burden of obesity.

PMID- 18070772
TI  - Central rather than overall obesity is related to diabetes in the Chinese
      population: the InterASIA study.
AB  - OBJECTIVE: The objective was to compare central and overall obesity measurements
      for identifying diabetes mellitus (DM) and impaired fasting glucose (IFG) level
      in the Chinese population. RESEARCH METHODS AND PROCEDURES: Data for 15,236
      Chinese adults between the ages of 35 and 74 years, obtained by the InterASIA
      Study in 2000-2001, were used for the current analyses. We analyzed the areas
      under the receiver operating characteristic (ROC) curves (AUCs) for waist
      circumference (WC), waist-to-hip ratio (WHR), and BMI to determine the ability of
      these indices to identify DM and IFG in the study sample and bootstrapped
      samples. WC was used as a measure of central obesity and BMI as a measure of
      overall obesity. RESULTS: The prevalence rates of central and overall obesity in
      the study population were 33.97% and 9.78%, respectively. The prevalence rates of
      IFG and DM were 7.34% and 5.51%, respectively. ROC analysis revealed significant
      differences between AUCs for WHR (0.666, 95% confidence interval, 0.647 to 0.685)
      and BMI (0.622, 95% confidence interval, 0.601 to 0.642) and for WC (0.661, 95%
      confidence interval, 0.643 to 0.682) and BMI for identifying DM (all p < 0.0001).
      The analysis also revealed significant differences between AUCs for WHR (0.638,
      95% confidence interval, 0.619 to 0.655) and BMI (0.607, 95% confidence interval,
      0.589 to 0.627) and for WC (0.637, 95% confidence interval, 0.615 to 0.654) and
      BMI for identifying IFG (all p < 0.001). DISCUSSION: Central obesity is more
      related to DM and IFG than is overall obesity in the Chinese population, and both
      WC and WHR are equally able to identify DM.

PMID- 18070773
TI  - The use of BMI and waist circumference as surrogates of body fat differs by
      ethnicity.
AB  - OBJECTIVE: To compare the prediction of percentage body fat using BMI and
      visceral adipose tissue (VAT) using waist circumference (WC) in individuals of
      Chinese, European, and South Asian origin. RESEARCH METHODS AND PROCEDURES:
      Healthy men and women of Chinese, European, and South Asian origin (n = 627)
      between the ages of 30 and 65 years were recruited to ensure equal distribution
      of gender and representation across BMI ranges (18.5 to 24.9, 25 to 29.9, and
      >or=30 kg/m(2)). Participants were assessed for demographics, anthropometry,
      lifestyle, and regional adiposity. Percentage body fat and VAT were measured by
      DXA and computer tomography scan, respectively. RESULTS: BMI and WC were highly
      correlated with total and regional measures of adiposity in each ethnic group. At
      any BMI, the percentage body fat of Chinese participants was similar to that of
      Europeans, but that of South Asians was greater by 3.9% (p < 0.001). Above a WC
      of 71.0 cm, the Chinese participants had an increasingly greater amount of VAT
      than the Europeans (p = 0.017 for interaction). South Asians had significantly
      more VAT than the Europeans at all but the most extreme WC (above 105 cm) (p <
      0.05). DISCUSSION: Compared with Europeans, percentage body fat was higher for a
      given BMI in South Asians, whereas VAT was higher for a given WC in both Chinese
      and South Asian men and women. These findings support the use of ethnic-specific
      anthropometric targets.

PMID- 18070774
TI  - Lipid and insulin levels in obese children: changes with age and puberty.
AB  - OBJECTIVE: The goal was to describe the lipid profile and insulin changes seen in
      obese children and adolescents at different stages of puberty. RESEARCH METHODS
      AND PROCEDURES: A cross-sectional study was conducted by chart review of 181
      obese (BMI > 95th) children and adolescents 5 to 17 years of age, who were
      referred to the Center for Atherosclerosis Prevention for cardiovascular risk
      reduction from January 2003 through December 2003. RESULTS: Eighty (44.2%)
      subjects were <12 years of age, and 101 (55.8%) were >or=12 years. Severity of
      obesity as expressed by BMI standard deviation score did not differ between these
      age groups. A significant difference with lower serum levels of total
      cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, and high-density lipoprotein cholesterol was seen with older age and
      with advancing sexual maturity rating. Triglycerides, very-low-density
      lipoprotein cholesterol, and lipoprotein(a) levels remained elevated across age
      and pubertal stages. Insulin levels and insulin resistance as expressed by
      homeostasis model assessment were significantly higher with older age. Similar
      trends were observed both in obese boys and obese girls during puberty.
      DISCUSSION: The most striking findings of this study are that in the 5- to 17
      year-old obese population, the combination of elevated triglycerides and very-low
      density lipoprotein cholesterol and low high-density lipoprotein cholesterol
      levels place them at greater cardiovascular risk than their non-obese peers, even
      when the changing patterns of lipids and lipoproteins seen during pubertal
      maturation are accounted for.

PMID- 18070775
TI  - Waist circumference and BMI cut-off based on 10-year cardiovascular risk:
      evidence for "central pre-obesity".
AB  - OBJECTIVE: The objective was to assess the waist circumference (WC) cut-off point
      that best identifies a level of 10-year cardiovascular disease (CVD) risk with
      optimal balance of sensitivity and specificity in Chinese subjects according to
      their predicted 10-year CVD risk. RESEARCH METHODS AND PROCEDURES: A community
      based cross-sectional observational study involving 14,919 Hong Kong Chinese
      subjects. The 10-year CVD risk based on various prediction models was calculated.
      The projected WC cut-off points were then determined. RESULTS: There were 4837
      (32.4%) men and 10,082 (67.6%) women (mean age +/- standard deviation, 47.3 +/-
      13.5 years; age range, 18 to 93 years; median age, 45.0 years). The mean optimal
      WC or BMI predicting a 15% to 30% 10-year CVD risk were 83 to 88 cm and 25
      kg/m(2) for men, and 76 cm and 23 kg/m(2) for women, respectively. With WC >or=90
      cm in men and >or=80 cm in women, the likelihood ratio at various WC cut-off
      points to develop a >or=20% 10-year CVD risk is 1.5 to 2.0 in men and 3.0 in
      women. The likelihood ratio was 1.5 in men with WC at 84 cm and in women at 70
      cm. DISCUSSION: Our results agree with the present guidelines on the definition
      of general and central obesity in Asia-Pacific regions. We propose the creation
      of an intermediate state of high WC, the "central pre-obesity" for Chinese men
      with WC >or=84 to 90 cm (>or=33 to 36 inches) and women with WC >or=74 to 80 cm
      (>or=29 to 32 inches). People with central pre-obesity, similar to those with
      overweight (BMI >or=23 to 25 kg/m(2)), already have an increased risk of co
      morbidities.

PMID- 18070776
TI  - Overweight and obesity: two predictors for worse early outcome in total hip
      replacement?
AB  - OBJECTIVE: Doctors and patients assume that overweight and obesity are negative
      predictors for good and excellent early outcome after total hip replacement. It
      was the purpose of this prospective investigation to assess whether overweight or
      obese patients have worse early postoperative outcome in comparison with normal
      weight patients. RESEARCH METHODS AND PROCEDURES: Sixty-seven consecutive
      patients receiving a total hip replacement were enrolled in the study. Patients
      were grouped into three samples according to BMI: normal-weight (BMI < 25
      kg/m(2), n = 11), overweight (BMI 25 to 29.9 kg/m(2), n = 36), and obese (BMI
      >or=30 kg/m(2), n = 20). At 10 days and at 3 months after surgery, the patient
      centered outcome was analyzed with a self-administered assessment chart, the
      Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index.
      Statistical analysis was performed with a multiple regression model that took
      into consideration further confounding parameters (age, sex, affected side,
      anchorage of the implant, duration of surgery, hospital length of stay, and prior
      pain, stiffness, and function). RESULTS: No significant influence of individual
      BMI on subjective outcome according to the WOMAC questionnaire was observed at
      either 10 days or 3 months after surgery. Hospital length of stay was comparable,
      and WOMAC scores did not differ significantly preoperatively, at 10 days, or at 3
      months postoperatively among patients with different BMI. DISCUSSION: These data
      showed that the BMI of the patients in our study sample had no significant impact
      on early outcome or hospital length of stay after total hip replacement. Our data
      suggest, therefore, that body weight should not be a justification for
      withholding surgery from overweight or obese patients.

PMID- 18070777
TI  - Obesity, white blood cell counts, and platelet counts among police officers.
AB  - OBJECTIVE: To determine the association between several obesity indices (BMI,
      waist circumference, waist-to-hip and waist-to-height ratios, and abdominal
      height) and hematologic parameters [white blood cell (WBC) and platelet counts]
      among police officers. RESEARCH METHODS AND PROCEDURES: The authors conducted
      this cross-sectional study among 104 randomly selected officers (41 women and 63
      men) from the Buffalo, NY, Police Department. Anthropometric measures were
      performed by clinic staff, and fasting blood samples were drawn for complete
      blood counts. Pearson's correlation, Student's t tests, ANOVA, analysis of
      covariance, and linear regression were used to assess the associations. RESULTS:
      Officers ranged in age from 26 to 61 years old and were predominantly white.
      Among women, current smokers had significantly higher WBC counts (7.4 x 10(3)
      cells/microL +/- 1.4) than former (5.2 x 10(3) cells/microL +/- 1.4) or never
      smokers (5.6 x 10(3) cells/microL +/- 1.5) (p = 0.002). Women had similar WBC
      counts but higher mean platelet counts than men (p = 0.005). Among women,
      abdominal height was positively associated with platelet count after adjustment
      for depression (p for trend = 0.039). Among women and men, a non-significant step
      wise trend was observed between abdominal height and mean WBC counts before and
      after adjustment for smoking, race, and physical activity. No association was
      observed between obesity and platelet count among men. DISCUSSION: Abdominal
      height was significantly associated with increased platelet counts among female
      officers. No significant associations were observed between obesity and WBC or
      platelet counts among male officers.

PMID- 18070778
TI  - Forecasting the obesity epidemic in the aging U.S. population.
AB  - OBJECTIVE: The objective was to forecast BMI distribution in the U.S. population
      along with demographic changes based on past race-, sex-, and birth cohort
      specific secular trends. RESEARCH METHODS AND PROCEDURES: We compiled data from
      44,184 subjects from 4 National Health and Nutrition Examination Surveys (NHANES;
      1971 to 2004). By race and sex, we fit regression models to create smoothed mean
      BMI curves by age for 1970 to 2010. Linking corresponding birth cohorts across
      age- and year-specific mean BMI projections, we estimated the trajectory of
      relative BMI throughout each cohort's lifetime. These projections were validated
      using actual cohorts in the Nurses' Health Study and Health Professionals Follow
      up Study. Combined with U.S. census, we predicted BMI distributions in 2010 and
      examined the joint impact of the obesity epidemic and population aging. RESULTS:
      BMI secular trends in the past 3 decades differ significantly by birth cohort,
      sex, and race. If these trends continue, the prevalence of obesity is expected to
      reach 35%, 36%, 33%, and 55% in 2010 among white men, white women, black men, and
      black women, respectively, far from the Healthy People 2010 goal of 15%. Such
      forecasts translate into 9.3 million more obese adults 20 to 74 years of age than
      in 2000, 8.3 million of whom would be 50 years of age or older, and 8.5 million
      of whom would be white. The mean age among obese men and women is also expected
      to rise from 47 to 49 years among whites and from 43 to 44 years among blacks.
      DISCUSSION: As the baby boom generation approaches retirement age, the continuing
      obesity epidemic signals a likely expansion in the population with obesity
      related comorbidities. A framework to combine BMI and demographic trends is
      essential in evaluating the burden and disparity associated with the epidemic in
      the aging U.S. population.

PMID- 18070779
TI  - A multimedia tool for the informed consent of patients prior to gastric banding.
AB  - OBJECTIVE: Severe obesity is a clear indication for appropriate, effective weight
      loss therapy. One option is operative intervention, e.g., gastric banding. Risks
      of the operation and therapeutic alternatives need to be comprehensibly presented
      to the patient. The literature has shown that better informed consent is obtained
      using information presented in a multimedia/video-based format. The current study
      developed and evaluated a multimedia program aimed at obtaining informed consent
      from obese patients before gastric banding. RESEARCH METHODS AND PROCEDURE: An
      interactive multimedia program was developed with information about preoperative
      examinations, the operation itself, hospital stay, operative risks, alternative
      therapies, and the pathophysiology and health risks of obesity. Two groups (Group
      1, n = 20, mean age 38 years, informed consent attained with conventional
      document information; Group 2, n = 20, mean age 37 years, informed consent
      attained with additional multimedia information) were interviewed regarding
      comprehensibility of the information presented, personal satisfaction, and
      anxiety levels during the informed consent process. RESULTS: Group 2 showed
      significantly better (p < 0.05) understanding of the presented information and
      higher levels of satisfaction with the informed consent process. Anxiety levels
      did not significantly differ between the two groups. DISCUSSION: Because patient
      satisfaction with the informed consent process and understanding of the presented
      information significantly improved, the multimedia program clearly benefits both
      surgeons and patients. Personal contact from the surgeon remains essential. High
      volumes of information presented in multimedia format do not alleviate patient
      anxiety, and personal contact may be beneficial.

PMID- 18070780
TI  - Patient-centred outcomes in clinical research: does it really matter?

PMID- 18070781
TI  - Thoracic epidural anaesthesia for cardiac surgery: are we missing the point?

PMID- 18070783
TI  - Sedation and regional anaesthesia in the adult patient.
AB  - This review discusses sedation for regional anaesthesia in the adult population.
      The first section deals with general aspects of sedation and shows that the
      majority of patients receiving sedation for regional anaesthesia are satisfied
      and would choose it again. Methods of assessing the level of sedation are
      discussed with emphasis on clinical measures. The pharmacology of the drugs
      involved in sedation is discussed, with propofol and remifentanil appearing to be
      the combination of choice for sedation in regional anaesthesia. The techniques
      for administering sedation are discussed and replacement of the traditional
      repeated boluses or continuous infusion with pharmacokinetic and patient
      controlled systems is supported. Patient satisfaction studies suggest that
      patient-controlled systems are preferred.

PMID- 18070784
TI  - Anaesthesia chapter from Saving mothers' lives; reviewing maternal deaths to make
      pregnancy safer.
AB  - This chapter concerning maternal mortality due to anaesthesia, reprinted with
      permission from Saving Mothers' Lives, is the 18th in a series of reports within
      the Confidential Enquiries into Maternal and Child Health (CEMACH) in the UK. In
      the years 2003-05 there were six women who died from problems directly related to
      anaesthesia, which is the same as the 2000-02 triennium. Obesity was a factor in
      four of these women who died. Two of these deaths were in women in early
      pregnancy, who received general anaesthesia for gynaecological surgery by
      inexperienced anaesthetists who failed to manage the airway and ventilation
      adequately. When trainee anaesthetists are relatively inexperienced their
      consultants must know the limits of their competence and when close supervision
      and help may be needed. One death was due to bupivacaine toxicity due to a drug
      administration error when a bag of dilute local anaesthetic was thought to be
      intravenous fluid. In a further 31 cases poor perioperative management may have
      contributed to death. Obesity was again a relevant factor. Other cases could be
      categorized into poor recognition of women being sick and poor clinical
      management of haemorrhage, sepsis and of pre-eclampsia. Early warning scores of
      vital signs may help identify the mother who is seriously ill. Learning points
      are highlighted in relation to the clinical management of these obstetric
      complications.

PMID- 18070785
TI  - Variation of bispectral index under TIVA with propofol in a paediatric
      population.
AB  - BACKGROUND: In this prospective observational study, we aim to explore the
      relationship between age and bispectral index (BIS) values at different plasma
      concentrations of propofol. METHODS: Fifty children aged from 3 to 15 yr were
      included. Anaesthesia was induced using a target-controlled infusion of propofol
      with the Kataria pharmacokinetic model together with a bolus of remifentanil
      followed by a continuous infusion rate at 0.2 microg kg(-1) min(-1). Target
      plasma propofol concentration was initially stabilized to 6 microg ml(-1) and
      continued for 6 min. The target was then decreased and stabilized to 4 microg ml(
      1) and then to 2 microg ml(-1). BIS values, plasma propofol concentration, and
      EEG were continuously recorded. In order to explore the relationship between
      variations in propofol concentration and the EEG bispectrum, we used a multiple
      correspondence analysis (MCA). Results are shown in median (range). RESULTS: We
      found no statistical difference between BIS values with propofol 6 microg ml(-1)
      [23 (12-40)] and 4 microg ml(-1) [28 (9-67)]. At 2 microg ml(-1), BIS was
      significantly different [52 (24-71)], but a significant correlation between the
      age of children and BIS values was found (r2=0.66; P<0.01). There was little
      change in children's position between 6 and 4 microg ml(-1) in the structure
      model of the MCA. From 4 to 2 microg ml(-1), the position of children moved only
      on axis 2. CONCLUSIONS: These results showed the difficulty to interpret BIS
      values because of the absence of significant change for higher plasma propofol
      concentration variation or because of the link with age for the lower plasma
      concentration.

PMID- 18070786
TI  - Spinal anaesthesia with articaine 5% vs bupivacaine 0.5% for day-case lower limb
      surgery: a double-blind randomized clinical trial.
AB  - BACKGROUND: A local anaesthetic with fast onset and short reliable duration of
      anaesthesia may be preferable for out-patient lower limb surgery. Articaine is
      believed to act faster and to have a shorter duration of action than bupivacaine,
      but there are no conclusive data available. The purpose of this study was to
      compare articaine and bupivacaine for day-case lower limb surgery. METHODS:
      Eighty patients planned for day-case lower limb surgery enrolled in this study.
      Patients were randomized to receive hyperbaric articaine 80 mg or plain
      bupivacaine 15 mg intrathecally. Primary outcome variable was recovery time from
      motor block. Secondary outcomes were: onset of sensory and motor block, maximum
      spread of sensory block, time to micturition, discharge from the hospital, and
      complications. RESULTS: The groups were comparable for the medians and the range
      of the maximum blocks after 30 min. Median time to complete regression of motor
      block was 101 min (range 80-129) for articaine compared with 307 min (range 225
      350) for bupivacaine (P<0.0005). First spontaneous micturition occurred after 257
      min (210-293) in the articaine group and after 350 min (304-370) in the
      bupivacaine group (P<0.0005). In the articaine and bupivacaine groups, patients
      were discharged after 300 min (273-347) and 380 min (332-431), respectively
      (P<0.0005). There was no significant difference in the occurrence of
      complications between the groups. CONCLUSIONS: Spinal anaesthesia with 80 mg of
      hyperbaric articaine has a shorter duration than a spinal anaesthesia with 15 mg
      of plain bupivacaine in lower limb surgery of approximately 1 h duration.

PMID- 18070787
TI  - Upper cervical spine movement during intubation: fluoroscopic comparison of the
      AirWay Scope, McCoy laryngoscope, and Macintosh laryngoscope.
AB  - BACKGROUND: The AirWay Scope (AWS) is a new fibreoptic intubation device, which
      allows visualization of the glottic structures without alignment of the oral,
      pharyngeal, and tracheal axes, and thus may be useful in patients with limited
      cervical spine (C-spine) movement. We fluoroscopically evaluated upper C-spine
      movement during intubation with the AWS or Macintosh or McCoy laryngoscope.
      METHODS: Forty-five patients, with normal C-spine, scheduled for elective surgery
      were randomly assigned to one of the three intubation devices. Movement of the
      upper C-spine was examined by measuring angles formed by adjacent vertebrae
      during intubation. Time to intubation was also recorded. RESULTS: Median
      cumulative upper C-spine movement was 22.3 degrees, 32.3 degrees, and 36.5
      degrees with the AWS, Macintosh laryngoscope, and McCoy laryngoscope,
      respectively (P<0.001, AWS vs, Macintosh and McCoy). The AWS reduced maximum
      movement of the C-spine at C1/C2 in comparison with the Macintosh or McCoy
      laryngoscope (P=0.012), and at C3/C4 in comparison with the McCoy laryngoscope
      (P=0.019). Intubation time was significantly longer in the AWS group than in the
      Macintosh group (P=0.03). CONCLUSIONS: Compared with the Macintosh or McCoy
      laryngoscope, the AWS produced less movement of upper C-spine for intubation in
      patients with a normal C-spine.

PMID- 18070788
TI  - Coronary artery stents and non-cardiac surgery.

PMID- 18070789
TI  - Coronary artery stents and non-cardiac surgery.

PMID- 18070790
TI  - Tracheo-oesophageal fistula and upper airway leak in the intensive care unit.

PMID- 18070791
TI  - Day case surgery and obesity: a changing perspective.

PMID- 18070792
TI  - Right molar approach to tracheal intubation in a child with Pierre Robin
      syndrome, cleft palate, and tongue tie.

PMID- 18070793
TI  - Post-intubation cricoarytenoid joint dysfunction.

PMID- 18070794
TI  - The Airway Scope, a new video laryngoscope: its use in three patients with
      cervical spine problems.

PMID- 18070797
TI  - Otto Klein--the forgotten founder of diagnostic cardiac catheterization.

PMID- 18070798
TI  - From measures to models: an evaluation of air pollution exposure assessment for
      epidemiological studies of pregnant women.
AB  - OBJECTIVES: To evaluate exposure estimation methods such as spatially resolved
      land-use regression models and ambient monitoring data in the context of
      epidemiological studies of the impact of air pollution on pregnancy outcomes.
      METHODS: The study measured personal 48 h exposures (NO, NO(2), PM(2.5) mass and
      absorbance) and mobility (time activity and GPS) for 62 pregnant women during
      2005-2006 in Vancouver, Canada, one to three times during pregnancy. Measurements
      were compared to modelled (using land-use regression and interpolation of ambient
      monitors) outdoor concentrations at subjects' home and work locations. RESULTS:
      Personal NO and absorbance (ABS) measurements were moderately correlated (NO: r =
      0.54, ABS: r = 0.29) with monitor interpolations and explained primarily within
      subject (temporal) variability. Land-use regression estimates including work
      location improved correlations for NO over those based on home postal code (for
      NO: r = 0.49 changed to NO: r = 0.55) and explained more between-subject variance
      (4-20%); limiting to a subset of samples (n = 61) when subjects spent >65% time
      at home also improved correlations (NO: r = 0.72). Limitations of the GPS
      equipment precluded assessment of including complete GPS-based mobility
      information. CONCLUSIONS: The study found moderate agreement between short-term
      personal measurements and estimates of ambient air pollution at home based on
      interpolation of ambient monitors and land-use regression. These results support
      the use of land-use regression models in epidemiological studies, as the ability
      of such models to characterise high resolution spatial variability is "reflected"
      in personal exposure measurements, especially when mobility is characterised.

PMID- 18070799
TI  - Low organic solvent exposure and combined maternal-infant gene polymorphisms
      affect gestational age.
AB  - OBJECTIVE: Little information is available on the associations of combined
      maternal-infant genetic susceptibility, environmental exposures and reproductive
      outcomes, especially in the Chinese population. The aim of this study was to
      investigate whether the polymorphisms of combined maternal-infant metabolic
      genes, CYP1A1 HincII, CYP1A1 MspI, GSTT1 and GSTM1 affect the association of
      maternal exposure to organic solvents with gestational age. METHODS: 1113 mother
      infant pairs were enrolled from the Beijing Yanshan Petrochemical Corporation
      between June 1997 and June 2002, of which 546 mothers were exposed to organic
      solvents and 567 were not. Multiple linear regression models were used to
      estimate the combined maternal-infant gene effects, and to characterise combined
      maternal-infant genetic susceptibility to organic solvents in relation to
      gestation. RESULTS: Organic solvent exposure was significantly related to
      shortened gestation (-1.2 weeks, 95% CI-1.6 to -0.9). Additionally, combined
      maternal-infant genotypes including Ile/Ile462-Ile/Ile462 (-0.6 weeks, 95% CI-0.9
      to -0.4) in CYP1A1 HincII and absent-absent in GSTT1 (-0.4 weeks, 95% CI-0.9 to 
      0.3) were significantly associated with shorter gestation. When considering both
      organic solvent exposure and combined maternal-infant genotypes, the largest
      associations were found among exposed women with the absent-absent genotype (-1.5
      weeks, 95% CI -1.8 to -1.2) in GSTT1 and the Ile/Ile462-Ile/Ile462 genotype (-1.5
      weeks, 95% CI -1.8 to -1.2) in CYP1A1 HincII, suggesting that combined genotypes
      would modify the effect of exposure to organic solvents on gestation.
      CONCLUSIONS: This study demonstrates the role of combined maternal-infant
      genotypes in modifying the adverse effects of organic solvent exposure on
      gestation, and the maternal-infant interaction of four genes was determined.

PMID- 18070800
TI  - Cervical muscle strength measurement is dependent on the location of thoracic
      support.
AB  - BACKGROUND: In all studies in which the strength of the neck extensor muscles has
      been measured, the level of thoracic support has been adjusted differently so
      direct comparison of the results is not possible. OBJECTIVE: To measure and
      compare the isometric force and isometric torque of neck extensor muscles at
      different levels of thoracic support. METHODS: Twenty healthy women volunteered
      for the study. The maximum isometric force of the neck extensor muscles was
      measured with the thoracic support located at five different levels. The highest
      level was set at the level of the spine of the scapula (level I) and the other
      levels were located 2.5 cm lower than the previous one, with the lowest level set
      10 cm below the highest level. The maximum isometric torque for each level was
      calculated by multiplying the isometric force by the length of the lever arm
      measured from the upper tip of the thoracic support to the centre point of the
      cell load at the occiput. RESULTS: The maximum isometric force and maximum
      isometric torque of the neck extensor muscles were increased step by step from
      130.5 N to 138.9 N, 141.9 N, 147.9 N and 155.4 N and from 33.7 Nm to 38.7 Nm,
      42.5 Nm, 47.2 Nm and 52.7 Nm, respectively. Except for the isometric force of the
      cervical extensor muscles measured at levels II and III, the differences between
      the other levels were significant (p<0.05). There was a significant correlation
      between isometric force and isometric torque measurements of the neck extensor
      muscles at different levels (0.81<r<0.96). CONCLUSION: Maximum isometric force
      and maximum isometric torque measurements of the neck extensor muscles vary with
      the length of the lever arm. It is recommended that a specific level of thoracic
      support should be used in follow-up and intervention studies. Setting the level
      of thoracic support at a specific level will make it possible to compare the
      strength of the neck extensor muscles in different studies. Measurements at the
      level of the spine of the scapula were easier and less time consuming.

PMID- 18070801
TI  - Effect of commercial airline travel on oxygen saturation in athletes.
AB  - BACKGROUND: Aircraft cabins are pressurised to maximum effective altitudes of
      2440 metres, resulting in significant decline in oxygen saturation in crew and
      passengers. This effect has not been studied in athletes. OBJECTIVE: To
      investigate the degree of decline in oxygen saturation in athletes during long
      haul flights. METHODS: A prospective cross-sectional study. National-level
      athletes were recruited. Oxygen saturation and heart rate were measured with a
      pulse oximeter at sea level before departure, at 3 and 7 hours into the flight,
      and again after arrival at sea level. Aircraft cabin pressure and altitude, cabin
      fraction of inspired oxygen and true altitude were also recorded. RESULTS: 45
      athletes and 18 healthy staff aged between 17 and 70 years were studied on 10
      long-haul flights. Oxygen saturation levels declined significantly after 3 hours
      and 7 hours (3-4%), compared with sea level values. There was an associated drop
      in cabin pressure and fraction of inspired oxygen, and an increase in cabin
      altitude. CONCLUSIONS: Oxygen saturation declines significantly in athletes
      during long-haul commercial flights, in response to reduced cabin pressure. This
      may be relevant for altitude acclimatization planning by athletes, as the time
      spent on the plane should be considered time already spent at altitude, with
      associated physiological changes. For flights of 10-13 hours in duration, it will
      be difficult to arrive on the day of competition to avoid the influence of these
      changes, as is often suggested by coaches.

PMID- 18070802
TI  - Two months of endurance training does not alter diastolic function evaluated by
      TDI in 9-11-year-old boys and girls.
AB  - OBJECTIVE: Superior global cardiac performance (ie stroke volume) is classically
      reported after training in children. Current knowledge of the impact of exercise
      training on myocardial relaxation, a major component of left ventricular (LV)
      filling and subsequently stroke volume, is, however, limited in the paediatric
      population. This study aimed to investigate the effect of aerobic training on LV
      wall motion velocities by tissue Doppler imaging (TDI) in healthy children.
      METHODS: 25 children (11 girls, 14 boys) were enrolled in a 2 month high
      intensity aerobic training programme and 25 (12 girls and 13 boys) served as
      controls. The children (9-11 years old) performed a graded maximal exercise test
      on a treadmill to evaluate maximal oxygen uptake. Standard Doppler
      echocardiography and TDI measurements were performed at baseline and end of the
      study. Tissue Doppler systolic, early and late myocardial velocities were
      obtained at the mitral annulus in the septal, lateral, inferior and posterior
      walls. RESULTS: Maximal oxygen uptake increased by 6.5% (before: 51.6 (SD 4.2),
      after: 55.0 (4.5) ml/min/kg p<0.001) after training. A modest but significant
      increase in left ventricular end-diastolic diameter was also noticed (before:
      46.1 (3.4), after: 48.3 (4.3) mm.BSA(-1/2), p<0.001), whereas left ventricular
      wall thickness and mass were unchanged. Neither transmitral inflow velocities nor
      early and late wall motion (Em: before = 18.4 (2.7), after = 18.0 (2.3) cm/s, Am:
      before = 6.8 (1.2), after = 6.7 (1.3) cm/s) were affected by training. Shortening
      fraction and regional systolic function (Sm: before = 10.1 (1.6), after = 10.2
      (1.4) cm/s) by TDI were also unchanged. CONCLUSION: High-intensity aerobic
      sessions repeated over a 2 month period failed to improve regional diastolic
      function assessed by TDI in healthy young children.

PMID- 18070803
TI  - Why does exercise terminate at the maximal lactate steady state intensity?
AB  - OBJECTIVE: The purpose of this study was to measure physiological responses
      during exercise performed until exhaustion at the exercise intensity
      corresponding to the maximal lactate steady state (MLSS) in order to determine
      why subjects stopped. METHODS: Eleven male trained subjects performed a test at
      MLSS on a cycle ergometer until exhaustion. RESULTS: Time to exhaustion was 55.0
      (SD 8.5) min. No variation was observed between the 10th and the last minute for
      arterial pyruvate, bicarbonate, and haemoglobin concentrations, redox state,
      arterial oxygen pressure, arterial oxygen saturation, osmolality, haematocrit,
      oxygen uptake, carbon dioxide output, and gas exchange ratio (p>0.05). Arterial
      lactate concentration and arterial carbon dioxide pressure decreased
      significantly whereas pH, base excess and the Ratings of Perceived Exertion (RPE)
      increased significantly (p<0.05). Although respiratory rate, minute ventilation
      and heart rate increased significantly until exhaustion (p<0.05), values at
      termination of the MLSS test were significantly lower than values measured during
      a maximal exercise test (p<0.05). Blood ammonia concentrations rose progressively
      during the MLSS test. However, there is no known mechanism by which this change
      could cause peripheral fatigue. CONCLUSIONS: Exercise termination was not
      associated with evidence of failure in any physiological system during prolonged
      exercise performed at MLSS. Thus the biological mechanisms of exercise
      termination at MLSS were compatible with an integrative homoeostatic control of
      peripheral physiological systems during exercise.

PMID- 18070804
TI  - Effects of exercise intensity on lymphocyte H2O2 production and antioxidant
      defences in soccer players.
AB  - OBJECTIVE: Physical exercise is capable of enhancing or suppressing the immune
      response depending on the intensity and duration of exercise. This study
      investigated how exercise intensity influences the lymphocyte antioxidant
      response and the induction of cellular oxidative damage. DESIGN: Eighteen
      voluntary male pre-professional soccer players participated in this study.
      Sportsmen played a 60 min training match, and were divided into three groups
      depending on the intensity degree during the match: low, medium and high
      intensities. MEASUREMENTS: Malondialdehyde (MDA), vitamins C and E and haem
      oxygenase-1 (HO-1) gene expression were measured in lymphocytes. Reactive oxygen
      species (ROS) production was determined in lymphocytes and neutrophils. RESULTS:
      Lymphocyte MDA levels and H(2)O(2) production were significantly increased in the
      group which performed the most intense exercise. Neutrophil counts and ROS
      production increased progressively with the exercise intensity. Vitamin C
      significantly decreased after exercise in the highest-intensity group in
      comparison with initial values, whereas vitamin E levels significantly increased
      in the medium and high-intensity groups. HO-1 gene expression significantly
      increased in the medium and high-intensity groups. CONCLUSIONS: Exercise
      intensity affects the lymphocyte and neutrophil oxidant/antioxidant balance, but
      only exercise of high intensity induces lymphocyte oxidative damage.

PMID- 18070805
TI  - The clinical utility of screening of biochemical parameters in elite athletes:
      analysis of 100 cases.
AB  - OBJECTIVE: To determine the clinical utility of screening for biochemical
      parameters in elite athletes. DESIGN: A prospective sequential case series.
      SETTING: The Department of Sports Medicine at the Australian Institute of Sport.
      PARTICIPANTS: 100 elite athletes from 11 sports (56 male and 44 female athletes,
      mean age 19 years, range 16-27), undergoing routine medical screening.
      INTERVENTION: Initial and follow-up assessment of the following biochemical
      parameters in association with clinical assessment; serum iron, ferritin,
      transferrin, percent transferrin saturation, sodium, potassium, chloride,
      calcium, magnesium, phosphate, urate, urea and creatinine, total protein,
      albumin, creatine kinase (CK), lactate dehydrogenase, aspartate aminotransaminase
      (AST), alanine aminotransferase, alkaline phosphatase, gamma-glutamyl
      transpeptidase, total bilirubin, cholesterol and triglycerides (non-fasting), and
      random glucose. RESULTS: 18 athletes showed no abnormalities on biochemical
      screening. 194 abnormal results were found in 82 athletes. 115 abnormalities were
      noted in 46 male and 79 in 36 female athletes. In 43 individual tests, the
      results did not return to normal on repeat testing. The most common abnormalities
      were increases in AST (27%), phosphate (13%), CK (13%), urea (12%) and bilirubin
      (12%). Three cases of hypercholesterolaemia and one case of haemochromatosis were
      identified, and one athlete, who was asymptomatic, was diagnosed with Epstein
      Barr virus infection, which was suspected because of an abnormal liver function
      test. The other abnormalities found appeared not to be of clinical significance.
      CONCLUSION: Most abnormalities found on routine biochemical screening in elite
      athletes are of no clinical significance, therefore such testing should, if used
      only for clinical purposes, be abandoned. When athletes are tested for iron
      status it would be prudent to include assessment of serum cholesterol in those
      with a family history of hyperlipidaemia.

PMID- 18070806
TI  - Short intensive exercise increases the migratory activity of mesenchymal stem
      cells.
AB  - BACKGROUND: It is known that exercise increases the number of stem cells within
      the circulation; however, it has not been clear which cellular processes are
      responsible for this increase. To answer this question, we analysed the influence
      of athletes' blood sera on human mesenchymal stem cells (MSC). METHODS: Sera were
      taken before and after short intensive exercise. As cellular parameters of MSC
      proliferation, apoptosis and migratory activity were analysed. RESULTS: A change
      in stimulation of proliferation or apoptosis was not seen after exercise. In
      contrast, the migratory activity of MSC was significantly increased after
      exercise. To identify potential factors that could be responsible for this
      effect, we also analysed the semiquantitative serum concentration of 120
      cytokines. Of these factors brain-derived neurotrophic factor, cutaneous T-cell
      attracting chemokine, epidermal growth factor receptor, glucocorticoid-induced
      tumour necrosis factor receptor ligand, growth-regulated oncogene-alpha,
      interleukin (IL)1a, IL6, IL8, IL15, pulmonary and activation-regulated chemokine
      and soluble tumour necrosis factor receptor II showed a significant increase
      whereas migration inhibitory factor howed a decrease in concentration after
      exercise. CONCLUSIONS: IL6 is known to stimulate migration in MSC. It is
      recognised that contracting skeletal muscles synthesise and release IL6 into the
      systemic circulation in response to exercise. We therefore hypothesise that there
      is a direct relationship between exercise, IL6 release and stem cell recruitment.

PMID- 18070808
TI  - Characteristics at haematoxylin and eosin staining of ruptures of the long head
      of the biceps tendon.
AB  - OBJECTIVE: To examine the relative prevalence of histological changes that have
      been found to be associated with the process of tendinopathy in lesions of the
      tendon of the long head of the biceps brachii and to evaluate the reliability of
      histopathological evaluation of tendon tissue in lesions of the tendon of the
      long head of the biceps. DESIGN: Tendon samples were taken from 51 patients (31
      men, 20 women; mean age 63.2 years) who underwent arthroscopic release of the
      long head of the biceps tendon because of refractory biceps tendinopathy and from
      5 male patients who died of cardiovascular events (mean age 69.6 years).
      Histological examination was performed using haematoxylin and eosin staining of
      sections, which were interpreted using a semiquantitative grading scale assessing
      fibre structure and arrangement, rounding of the nuclei, regional variations in
      cellularity, increased vascularity, decreased collagen staining and
      hyalinisation. RESULTS: The mean (SD) pathological sum score of ruptured tendons
      was greater than that of control tendons (15.76 (3.11) vs 3.4 (1.9), p<0.001).
      Within each specific category of tendon abnormalities, the chi(2) test showed
      significant differences between the control and ruptured tendons; all the
      variables were significantly different (Mann-Whitney U test 0.05, p<0.001). Using
      the kappa statistic, the agreement between the two readings ranged from 0.53 to
      0.85. CONCLUSIONS: Unruptured tendons of the long head of the biceps, even at an
      advanced age and ruptured tendons of the long head of the biceps are clearly part
      of two distinct populations.

PMID- 18070807
TI  - Fast and slow myosins as markers of muscle injury.
AB  - OBJECTIVE: The diagnosis of muscular lesions suffered by athletes is usually made
      by clinical criteria combined with imaging of the lesion (ultrasonography and/or
      magnetic resonance) and blood tests to detect the presence of non-specific muscle
      markers. This study was undertaken to evaluate injury to fast and slow-twitch
      fibres using specific muscle markers for these fibres. METHODS: Blood samples
      were obtained from 51 non-sports people and 38 sportsmen with skeletal muscle
      injury. Western blood analysis was performed to determine fast and slow myosin
      and creatine kinase (CK) levels. Skeletal muscle damage was diagnosed by physical
      examination, ultrasonography and magnetic resonance and biochemical markers.
      RESULTS: The imaging tests were found to be excellent for detecting and
      confirming grade II and III lesions. However, grade I lesions were often
      unconfirmed by these techniques. Grade I lesions have higher levels of fast
      myosin than slow myosin with a very small increase in CK levels. Grade II and III
      lesions have high values of both fast and slow myosin. CONCLUSIONS: The
      evaluation of fast and slow myosin in the blood 48 h after the lesion occurs is a
      useful aid for the detection of type I lesions in particular, since fast myosin
      is an exclusive skeletal muscle marker. The correct diagnosis of grade I lesions
      can prevent progression of the injury in athletes undergoing continual training
      sessions and competitions, thus aiding sports physicians in their decision
      making.

PMID- 18070809
TI  - Sports medicine clinical trial research publications in academic medical journals
      between 1996 and 2005: an audit of the PubMed MEDLINE database.
AB  - OBJECTIVE: To identify sports medicine-related clinical trial research articles
      in the PubMed MEDLINE database published between 1996 and 2005 and conduct a
      review and analysis of topics of research, experimental designs, journals of
      publication and the internationality of authorships. HYPOTHESIS: Sports medicine
      research is international in scope with improving study methodology and an
      evolution of topics. DESIGN: Structured review of articles identified in a search
      of a large electronic medical database. SETTING: PubMed MEDLINE database.
      PARTICIPANTS: Sports medicine-related clinical research trials published between
      1996 and 2005. INTERVENTIONS: Review and analysis of articles that meet inclusion
      criteria. MAIN OUTCOME MEASUREMENTS: Articles were examined for study topics,
      research methods, experimental subject characteristics, journal of publication,
      lead authors and journal countries of origin and language of publication.
      RESULTS: The search retrieved 414 articles, of which 379 (345 English language
      and 34 non-English language) met the inclusion criteria. The number of
      publications increased steadily during the study period. Randomised clinical
      trials were the most common study type and the "diagnosis, management and
      treatment of sports-related injuries and conditions" was the most popular study
      topic. The knee, ankle/foot and shoulder were the most frequent anatomical sites
      of study. Soccer players and runners were the favourite study subjects. The
      American Journal of Sports Medicine had the highest number of publications and
      shared the greatest international diversity of authorships with the British
      Journal of Sports Medicine. The USA, Australia, Germany and the UK produced a
      good number of the lead authorships. In all, 91% of articles and 88% of journals
      were published in English. CONCLUSIONS: Sports medicine-related research is
      internationally diverse, clinical trial publications are increasing and the
      sophistication of research design may be improving.

PMID- 18070810
TI  - Left atrial myocardial function in either physiological or pathological left
      ventricular hypertrophy: a two-dimensional speckle strain study.
AB  - BACKGROUND: Atrial function is an integral part of cardiac function that is often
      neglected. The presence of left ventricule hypertrophy (LVH) due to arterial
      hypertension may impair atrial function. However, it has also been suggested that
      physical training attenuates the age-associated impairment of diastolic filling.
      This study investigated whether mechanical dysfunction in the left atrium (LA) is
      present in patients with either physiological or pathological LVH, using two
      dimensional strain rate imaging (2D strain echocardiography; 2DSE). METHODS:
      Standard echocardiography, exercise stress echo and 2DSE of the left atrium were
      performed in 40 patients with arterial hypertension, 45 age-matched elite
      athletes (>40 years) and 25 healthy sedentary controls. Atrial longitudinal
      strain was performed from the apical views for the basal segments of the LA
      septum, lateral wall and roof. RESULTS: LV mass index and ejection fraction were
      comparable between patients with either physiological or pathological LVH. Elite
      athletes showed increased LV end-diastolic diameter, end-diastolic volume and
      stroke volume, whereas circumferential end-systolic stress was higher in patients
      with hypertension. LA diameter and maximum volume were increased but similar
      between the two groups of patients with LVH. LA active emptying volume and
      fraction were both higher in patients with hypertension. Conversely, peak
      systolic myocardial atrial strain was significantly reduced in patients with
      pathological LVH compared with controls and athletes for all the analysed atrial
      segments (p<0.0001). Using multivariate analysis, LV end-diastolic volume/body
      surface area (BSA) (beta coefficient 0.52; p<0.0001) and LV mass (beta = 0.48;
      p<0.001) in athletes emerged as the only independent determinants of LA lateral
      wall peak systolic strain. In contrast, in patients with hypertension, an
      independent negative association of LA lateral wall peak systolic strain with
      both LV mass (beta = -0.42; p<0.001) and circumferential end-systolic stress
      (beta = -0.43; p<0.001) was found. In addition, in the overall population of
      patients with LVH, LA lateral wall systolic strain (beta = 0.49; p<0.0001) was a
      powerful independent predictor of maximum workload during exercise testing.
      CONCLUSIONS: 2DSE represents a promising, non-invasive, simple and reproducible
      technique to assess LA myocardial function in patients with either physiological
      or pathological LVH. LA myocardial deformation is impaired in patients with
      hypertension compared with age-matched sedentary controls and elite athletes, and
      is closely associated with functional capacity during effort.

PMID- 18070811
TI  - Internal impingement in the tennis player: rehabilitation guidelines.
AB  - Internal impingement is a commonly described cause of shoulder pain in the
      overhead athlete, particularly in tennis players. Three shoulder dysfunctions,
      often correlated with internal impingement symptoms, require attention in the
      rehabilitation strategy of internal impingement in the tennis player: (1)
      acquired glenohumeral anterior instability, (2) loss of internal rotation range
      of motion, and (3) lack of retraction strength. Based on recent literature, the
      following guidelines are proposed in the rehabilitation of the tennis player with
      internal impingement symptoms: (1) shoulder rehabilitation should be integrated
      into kinetic chain training, not only in the advanced phases of the athlete's
      rehabilitation, but from the initial phases; (2) both angular and translational
      mobilisations can be used in the treatment of acquired loss of glenohumeral
      internal rotation range of motion to stretch the posterior structures of the
      glenohumeral joint; and 3) in the rehabilitation of scapular dyskinesis, the
      therapist should focus on restoration of intramuscular trapezius muscle balance
      in the scapular exercises, with special attention to strength training of the
      retractors.

PMID- 18070812
TI  - Characteristics trends, mortality and morbidity in persons newly diagnosed HIV
      positive during the last decade: the profile of new HIV diagnosed people.
AB  - We analysed mortality, morbidity and trends in the characteristics, including
      risk factors of late testing, in 6805 the patients newly diagnosed for HIV
      infection between 1 January 1996 and 1 July 2006. The proportion of individuals
      in high risk groups of infection, as MSM, has decreased over time whereas the
      proportion of those in low risk of infection, as heterosexual persons in couple
      with children, has increased. This population is mainly diagnosed late with major
      consequences on morbidity and mortality.

PMID- 18070813
TI  - Repair of aortic arch and the impact of cross-clamping time, New York Heart
      Association stage, circulatory arrest time, and age on operative outcome.
AB  - BACKGROUND: Aortic arch replacement is associated with high morbidity and
      mortality. METHODS: We evaluated the postoperative complications and risk factors
      in 32 consecutive patients after aortic arch replacement. RESULTS: The mean age
      was 61+/-15 years and male to female ratio was 24/8. Diameter of ascending aorta
      was 6.0+/-0.8 cm and diameter of aortic arch was 5.2+/-1.2 cm. The average New
      York heart association (NYHA) class was 2+/-1. The 30-day mortality was 6.2% (2
      of 32 patients), one patient died intraoperatively (3%); all surviving 30
      patients had f/u for at least six months, a total of 3 of 32 patients had died
      within six months, actuarial survival was 90% at six months. The overall
      incidence of neurologic adverse events was 9%; however, only one patient had a
      cerebrovascular accident (CVA) with a focal deficit (3%). The other two patients
      had global neurologic dysfunction. Other significant postoperative complications
      included atrial fibrillation in 15 patients (46%), ventricular fibrillation
      requiring cardiopulmonary resuscitation (CPR) in one patient (3%), and
      pericardial effusion requiring pericardicentesis in eight patients (25%). The
      need for blood transfusion correlated with the cross-clamping length (Pearson r
      0.62; 95% confidence interval (CI), 0.35-0.79; P-value 0.0001; R(2)=0.38). Cross
      clamp time (139+/-58 min) did not have an impact on length of intensive care unit
      (ICU) stay (Pearson r -0.09; 95% CI -0.39-0.23; P=0.58; R(2)=0.008) nor did the
      length of circulatory arrest (95% CI -0.44-0.21, P=0.44). The length of stay in
      the ICU (142+/-128 h) correlated with the NYHA stage of the patient (95% CI 0.001
      0.62, P=0.04). The length of stay (LOS) (12+/-6 days) correlated with age of the
      patients (95% CI 0.03-0.57, P=0.03). CONCLUSION: Elderly patients and patients
      with high NYHA class need close postoperative monitoring in the ICU. A short
      circulatory arrest and aortic clamp time do not extend the LOS in ICU or in the
      hospital.

PMID- 18070814
TI  - Rationale, design, and methodology of the Women's Genome Health Study: a genome
      wide association study of more than 25,000 initially healthy american women.
AB  - The primary aim of the Women's Genome Health Study (WGHS) is to create a
      comprehensive, fully searchable genome-wide database of >360 000 single
      nucleotide polymorphisms among at least 25 000 initially healthy American women
      participating in the ongoing NIH-funded Women's Health Study (WHS). These women
      have already been followed over a 12-year period for major incident health events
      including but not limited to myocardial infarction, stroke, cancer, diabetes,
      osteoporosis, venous-thromboembolism, cognitive decline, and common visual
      disorders such as age- related macular degeneration and cataracts. Investigations
      within the WGHS will seek to identify relevant patterns of genetic polymorphism
      that predict future disease states in otherwise healthy American women, and to
      evaluate patterns of genetic polymorphism that relate to multiple intermediate
      phenotypes including blood-based determinants of disease that were measured at
      baseline for each study participant. By linking genome-wide data to the existing
      epidemiologic databank of the parent WHS, which includes comprehensive dietary,
      behavioral, and traditional exposure data on each participant since cohort
      inception in 1992, the WGHS will also allow exploration of gene-environment and
      gene-gene interactions as they relate to incident disease states. Thus, with
      continued follow-up of the WHS, the WGHS provides a unique scientific resource-a
      full-cohort, prospective, genome-wide association study among initially healthy
      American women.

PMID- 18070815
TI  - Effect of homocysteine concentration in early pregnancy on gestational
      hypertensive disorders and other pregnancy outcomes.
AB  - BACKGROUND: Increased total homocysteine (tHcy) may be associated with placental
      mediated adverse pregnancy outcomes, but few prospective studies have measured
      tHcy before pregnancy outcome. This study was undertaken to determine whether
      increased tHcy measured in early pregnancy is associated with pregnancy loss,
      gestational hypertension (GH), preeclampsia, or small for gestational age (SGA)
      infants. METHODS: We conducted a prospective cohort study between 2002 and 2005.
      We measured tHcy and serum folate in blood samples from pregnant women (<20
      weeks' gestation) and collected detailed pregnancy information through a
      questionnaire and medical record review. RESULTS: Of the 2119 women included in
      the study, 103 had a pregnancy loss, 115 had gestational hypertension, 65 had
      preeclampsia, and 129 had an SGA infant. Subjects with increased tHcy
      concentrations were at increased risk of pregnancy loss [relative risk (RR) 2.1,
      95% CI 1.2-3.6] or preeclampsia (RR 2.7, 95% CI 1.4-5.0) than subjects with lower
      tHcy concentrations, but increased tHcy concentration was not associated with
      increased risk of developing GH or having an SGA infant. CONCLUSION: The finding
      of high tHcy in early pregnancy as a risk factor for pregnancy loss and
      preeclampsia is consistent with a hypothesis that increased tHcy results in
      abnormalities of the placental vasculature.

PMID- 18070816
TI  - Bloodspot assay using HPLC-tandem mass spectrometry for detection of Barth
      syndrome.
AB  - BACKGROUND: Barth syndrome (BTHS) is a serious X-linked, metabolic, multisystem
      disorder characterized by cardiomyopathy, neutropenia, myopathy, and growth
      delay. Because early diagnosis and appropriate treatment are of key importance
      for the survival of affected boys, we developed a biochemical BTHS screening
      method based on analysis of the monolysocardiolipin:cardiolipin ratio in
      bloodspots. METHODS: We performed chloroform/methanol extraction on quarter-inch
      punches of dried bloodspots on Guthrie cards from BTHS patients and controls.
      Extracts were dried (60 degrees C, N(2)) and reconstituted in
      CHCl(3)/methanol/H(2)O [50:45:5 vol/vol/vol, 0.1% NH(3) (25%)]. HPLC-tandem mass
      spectrometry analysis was performed with a normal-phase HPLC column and multiple
      reaction monitoring transitions for monolysocardiolipin (MLCL) and cardiolipin
      (CL) with a total run time of 10 min. The ratio of MLCL and CL was used as
      screening parameter. RESULTS: All BTHS patients (n = 31) had
      monolysocardiolipin:cardiolipin ratios >0.40 and all controls (n = 215) had
      monolysocardiolipin:cardiolipin ratios <0.23. Using a cutoff point of 0.30, a
      blind test of 206 samples (199 controls, 7 BTHS) had sensitivity and specificity
      of 100%. Bloodspots could be stored at 4 degrees C or room temperature for >1
      year without affecting the test outcome. Three neonatal Guthrie cards of BTHS
      patients taken 3.6 to 5.8 years previously were correctly identified as positive
      for BTHS. CONCLUSIONS: HPLC-tandem mass spectrometry analysis of dried bloodspots
      is an unambiguous screening test for BTHS with potential for rapid screening of
      neonates suspected of having BTHS, making remote and retrospective diagnosis
      accessible for a disease that is almost certainly underdiagnosed.

PMID- 18070817
TI  - Evaluation of endometrial urocortin secretion for prediction of pregnancy after
      intrauterine insemination.
AB  - BACKGROUND: Urocortin is a neuropeptide produced by the human endometrium and has
      biological effects putatively important for promoting blastocyst implantation. We
      measured urocortin concentrations in samples of endometrial wash fluid collected
      from women with unexplained infertility who underwent intrauterine insemination
      (IUI). METHODS: Patients 28-42 years of age (n = 71) were consecutively enrolled
      after a complete clinical evaluation. Endometrial wash fluid was retrieved before
      IUI, at the time of ultrasound evaluation of endometrial thickness. Urocortin
      concentrations were assayed with a specific ELISA. RESULTS: After IUI, 28
      patients (39%) became pregnant. Urocortin concentrations were significantly
      higher in women who became pregnant than in those who did not (0.38 microg/L vs
      0.13 microg/L, P <0.0001). At a cutoff of 0.321 microg/L, urocortin results were
      positive in 61% [95% confidence interval (CI), 41%-78%] of women who had
      successful implantation and negative in 98% (95% CI, 88%-99.6%) of those who did
      not. The pregnancy rate for women with urocortin concentrations >0.32 microg/L
      was 94%, which differed significantly (P <0.05) from the overall pregnancy rate
      of 39% in the study population. CONCLUSIONS: Urocortin is measurable in
      endometrial wash fluid, and its concentrations before IUI are higher in women who
      subsequently achieve pregnancy. These data suggest that the probability of having
      a successful pregnancy-producing IUI may be better estimated by measuring
      urocortin in endometrial wash fluid.

PMID- 18070818
TI  - Noninvasive optical, electrical, and acoustic methods of total hemoglobin
      determination.
AB  - BACKGROUND: Anemia is an underdiagnosed, significant public health concern
      afflicting >2 billion people worldwide. The detrimental effects of tissue oxygen
      deficiency on the cardiovascular system and concurrent appearance of anemia with
      numerous high-risk disorders highlight the importance of clinical screening.
      Currently there is no universally accepted, clinically applicable, noninvasive
      hemoglobin/hematocrit screening tool. The need for such a device has prompted an
      investigation into a breadth of techniques. METHODS: A synopsis of the literature
      and current directions of research in noninvasive total hemoglobin measurement
      was collected. Contributions highlighted in this review are limited to those
      studies conducted with a clinical aspect, and most include in vivo patient
      studies. RESULTS: The review of potential techniques presented here includes
      optoacoustic spectroscopy, spectrophotometric imaging, diffuse reflectance
      spectroscopy, transcutaneous illumination, electrical admittance plethysmography,
      and photoplethysmography. The technological performance, relative benefits of
      each approach, potential instrumentation design considerations, and future
      directions are discussed in each subcategory. CONCLUSIONS: Many techniques
      reviewed here have shown excellent accuracy, sensitivity, and specificity in
      measuring hemoglobin/hematocrit, thus in the near future a new clinically viable
      tool for noninvasive hemoglobin/hematocrit monitoring will likely be widely used
      for patient care. Limiting factors in clinical adoption will likely involve
      technology integration into the current standard of care in each field routinely
      dealing with anemia.

PMID- 18070819
TI  - Simultaneous assessment of endothelial function, nitric oxide synthase activity,
      nitric oxide-mediated signaling, and oxidative stress in individuals with and
      without hypercholesterolemia.
AB  - BACKGROUND: Endothelial function is impaired in hypercholesterolemia and
      atherosclerosis. Based on mostly indirect evidence, this impairment is attributed
      to reduced synthesis or impaired biological activity of endothelium-derived
      nitric oxide (NO). It was the aim of this study to directly estimate and compare
      whole-body NO production in normo- and hypercholesterolemia by applying a
      nonradioactive stable isotope dilution technique in vivo. METHODS: We enrolled 12
      normocholesterolemic and 24 hypercholesterolemic volunteers who were all
      clinically healthy. To assess whole-body NO synthesis, we intravenously
      administered l-[guanidino-((15)N(2))]-arginine and determined the urinary
      excretion of (15)N-labeled nitrate, the specific end product of NO oxidation in
      humans, by use of gas chromatography-mass spectrometry. In addition, we measured
      flow-mediated vasodilation (FMD) of the brachial artery, expression of
      endothelial NOS (eNOS) in platelets, plasma concentration of the endogenous NOS
      inhibitor asymmetric dimethylarginine (ADMA), and urinary excretion of 8
      isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)). RESULTS: After infusion of l
      [guanidino-((15)N(2))]-arginine, cumulative excretion of (15)N-labeled-nitrate
      during 48 h was 40% [95% CI 15%-66%] lower in hypercholesterolemic than
      normocholesterolemic volunteers [mean 9.2 (SE 0.8) micromol vs 15.4 (2.3)
      micromol/l, P = 0.003]. FMD was on average 36% [4%-67%] lower in
      hypercholesterolemic than normocholesterolemic volunteers [6.3 (4.0)% vs 9.4
      (4.6)%, P = 0.027]. Normalized expression of NOS protein in platelets was also
      significantly lower in hypercholesterolemic volunteers, whereas there were no
      significant differences in plasma ADMA concentration or urinary excretion of 8
      iso-PGF(2alpha) between the 2 groups. CONCLUSIONS: This study provides direct
      evidence for a decreased whole body NO synthesis rate in healthy people with
      hypercholesterolemia.

PMID- 18070820
TI  - Induced differentiation and maturation of newborn liver cells into functional
      hepatic tissue in macroporous alginate scaffolds.
AB  - The present work explores cell cultivation in macroporous alginate scaffolds as a
      means to reproduce hepatocyte terminal differentiation in vitro. Newborn rat
      liver cell isolates, consisting of proliferating hepatocytes and progenitors,
      were seeded at high cell density of 125 x 10(6)/cm(3) within the scaffold and
      then cultivated for 6 wk in chemically defined medium. Within 3 days, the
      alginate-seeded cells expressed genes for mature liver enzymes, such as
      tryptophan oxygenase, secreted a high level of albumin, and performed phase I
      drug metabolism. The cells formed compacted spheroids, establishing homotypic and
      heterotypic cell-to-cell interactions. By 6 wk, the spheroids developed into
      organoids, with an external mature hepatocyte layer covered by a laminin layer
      encasing inner vimentin-positive cells within a laminin-rich matrix also
      containing collagen. The hepatocytes presented a distinct apical surface between
      adjacent cells and a basolateral surface with microvilli facing extracellular
      matrix deposits. By contrast, viable adherent cells within collagen scaffolds
      presenting the identical porous structure did not express adult liver enzymes or
      secrete albumin after 6 wk. This study thus illustrates the benefits of cell
      cultivation in macroporous alginate scaffolds as an effective promoter for the
      maturation of newborn liver cells into functional hepatic tissue, capable of
      maintaining prolonged hepatocellular functions.

PMID- 18070821
TI  - The taste transduction channel TRPM5 is a locus for bitter-sweet taste
      interactions.
AB  - Ordinary gustatory experiences, which are usually evoked by taste mixtures, are
      determined by multiple interactions between different taste stimuli. The most
      studied model for these gustatory interactions is the suppression of the
      responses to sweeteners by the prototype bitter compound quinine. Here we report
      that TRPM5, a cation channel involved in sweet taste transduction, is inhibited
      by quinine (EC(50)=50 microM at -50 mV) owing to a decrease in the maximal whole
      cell TRPM5 conductance and an acceleration of channel closure. Notably, quinine
      inhibits the gustatory responses of sweet-sensitive gustatory nerves in wild-type
      (EC(50)= approximately 1.6 mM) but not in Trpm5 knockout mice. Quinine induces a
      dose- and time-dependent inhibition of TRPM5-dependent responses of single sweet
      sensitive fibers to sucrose, according to the restricted diffusion of the drug
      into the taste tissue. Quinidine, the stereoisomer of quinine, has similar
      effects on TRPM5 currents and on sweet-induced gustatory responses. In contrast,
      the chemically unrelated bitter compound denatonium benzoate has an approximately
      100-fold weaker effect on TRPM5 currents and, accordingly, at 10 mM it does not
      alter gustatory responses to sucrose. The inhibition of TRPM5 by bitter compounds
      constitutes the molecular basis of a novel mechanism of taste interactions,
      whereby the bitter tastant inhibits directly the sweet transduction pathway.

PMID- 18070822
TI  - Chronic nicotine in utero selectively suppresses hypoxic sensitivity in neonatal
      rat adrenal chromaffin cells.
AB  - Nicotine in cigarette smoke has been linked to several deleterious side effects
      on the offspring of smoking mothers, including impaired development of the
      sympathoadrenal system, abnormal arousal reflexes, and sudden infant death
      syndrome. Catecholamine (CA) release from adrenomedullary chromaffin cells (AMCs)
      in response to asphyxial stressors, e.g., low O(2) (hypoxia) and elevated CO(2)
      (hypercapnia), is critical for adaptation to extrauterine life and occurs before
      splanchnic innervation. Here, we investigated the effects of prenatal nicotine
      bitartrate exposure on the ability of neonatal (P0) rat AMCs to respond
      appropriately to asphyxial stressors. Control AMCs isolated from pups born to
      saline-treated dams displayed typical responses to hypoxia and hypercapnia,
      including inhibition of outward K(+) current, membrane depolarization, increased
      cytosolic calcium, and CA secretion. In contrast, P0 AMCs from pups born to
      nicotine-treated dams showed a marked suppression or loss of hypoxic sensitivity,
      although hypercapnic sensitivity and the expression of CO(2) markers (i.e.,
      carbonic anhydrase I and II) appeared normal. Moreover, isolated saline-treated
      P0 AMCs lost their hypoxic sensitivity when grown in culture for approximately 1
      wk in the presence of a subsaturating concentration of nicotine base (50 microM),
      and this effect was abolished by the nicotinic acetylcholine receptor (nAChR)
      blocker mecamylamine (100 microM). Taken together, these data suggest that the
      adverse effects of maternal smoking on sympathoadrenal function in the offspring
      are due in part to a loss or suppression of acute hypoxic sensitivity in adrenal
      chromaffin cells, triggered by the direct action of nicotine on endogenous
      nicotinic acetylcholine receptors.

PMID- 18070823
TI  - Percutaneous needle biopsy of lung nodules under CT fluoroscopic guidance with
      use of the "I-I device".
AB  - The aim of this study is to evaluate the feasibility and safety of CT
      fluoroscopic-guided needle biopsy with the use of the "I-I device", which was
      developed to assist in precisely advancing the needle while avoiding irradiation
      to the operator's hand. Using the "I-I device" under CT fluoroscopic guidance,
      131 percutaneous needle lung biopsies were performed followed by
      histopathological evaluation. The final diagnosis was confirmed by independent
      surgical pathological findings or clinical follow-up. The rate of success in
      obtaining specimens adequate for histopathological analysis was 100% (131/131).
      For the 104 lesions that we were able to follow up, sensitivity, specificity and
      accuracy in diagnosing malignancy were 93.8%, 100% and 95.2%, respectively. In 51
      lesions for which surgery was performed, the specific cell type was characterized
      in 98.0% (50/51; malignant, n = 38; benign, n = 12). The specific cell type was
      precisely diagnosed and confirmed after surgery in 36 malignant lesions and 8
      benign lesions. Biopsy-induced complications were pneumothorax in 34.0% (44/131)
      and haemoptysis in 9.9% (13/131). None of the patients had serious complications.
      In conclusion, CT fluoroscopic-guided lung biopsy with use of the "I-I device"
      provides a high degree of diagnostic accuracy, allows specific characterization
      of lung nodules and can be performed safely.

PMID- 18070824
TI  - Measurement of pharmacokinetic parameters in histologically graded invasive
      breast tumours using dynamic contrast-enhanced MRI.
AB  - Dynamic contrast-enhanced MRI (DCE-MRI) has demonstrated high sensitivity for
      detection of breast cancer. Analysis of correlation between quantitative DCE-MRI
      findings and prognostic factors (such as histological tumour grade) is important
      for defining the role of this technique in the diagnosis of breast cancer as well
      as the monitoring of neoadjuvant therapies. This paper presents a practical
      clinical application of a quantitative pharmacokinetic model to study
      histologically confirmed and graded invasive human breast tumours. The hypothesis
      is that, given a documented difference in capillary permeability between benign
      and malignant breast tumours, a relationship between permeability-related DCE-MRI
      parameters and tumour aggressiveness persists within invasive breast carcinomas.
      In addition, it was hypothesized that pharmacokinetic parameters may demonstrate
      stronger correlation with prognostic factors than the more conventional black-box
      techniques, so a comparison was undertaken. Significant correlations were found
      between pharmacokinetic and black-box parameters in 59 invasive breast
      carcinomas. However, statistically significant variation with tumour grade was
      demonstrated in only two permeability-related pharmacokinetic parameters: k(ep)
      (p<0.05) and K(trans) (p<0.05), using one-way analysis of variance. Parameters
      k(ep) and K(trans) were significantly higher in Grade 3 tumours than in low-grade
      tumours. None of the measured DCE-MRI parameters varied significantly between
      Grade 1 and Grade 2 tumours. Measurement of k(ep) and K(trans) might therefore be
      used to monitor the effectiveness of neoadjuvant treatment of high-grade invasive
      breast carcinomas, but is unlikely to demonstrate remission in low-grade tumours.

PMID- 18070825
TI  - Thoracic paravertebral block for analgesia following liver mass radiofrequency
      ablation.
AB  - A 66-year-old man presented for a second attempt of radiofrequency ablation of a
      metastatic carcinoid liver lesion. The first attempt using intravenous sedation
      was unsuccessful because of inadequate pain control and subsequent patient
      combativeness. Despite fentanyl being given during general anaesthesia, the
      patient complained of severe right flank pain after emergence. A thoracic
      paravertebral block was performed without complication and the patient's pain
      decreased to "3 out of 10" on a standard 10-point scale after 10 min, and "0 out
      of 10" after 30 min. The patient's pain score remained 0 throughout the following
      day, and no further analgesics were required. Thoracic paravertebral block can
      provide complete and lasting analgesia following hepatic radiofrequency ablation,
      and warrants further study for patients undergoing hepatic radiological
      interventions.

PMID- 18070826
TI  - A morphological index for assessing hip osteoarthritis severity from radiographic
      images.
AB  - A new method is proposed for assessing the severity of hip osteoarthritis (OA)
      based on radiographic hip joint space (HJS) morphology. 64 hips of patients with
      verified unilateral OA or bilateral OA were studied by digitizing the
      corresponding pelvic radiographs. Radiographic OA severity was assessed employing
      the Kellgren and Lawrence (KL) scale. Using custom-developed software,
      radiographs were enhanced, the margins of both HJSs were outlined, and 64 regions
      of interest (ROIs), corresponding to the delineated HJSs, were obtained.
      Employing custom-developed algorithms, an index ("joint space morphological
      index" - JSMI) evaluating alterations in the shape and size of HJS was
      introduced, calculated and normalized with respect to each patient's individual
      anatomy. The JSMI values were used to introduce classification rules concerning
      the characterization of a hip in accordance with the KL scale. For each patient
      in the unilateral OA group, the OA severity was expressed as the percentage of
      the HJS area difference between the patient's osteoarthritic and contralateral
      normal hip. The per cent HJS area difference and the JSMI values were used in the
      design of a regression model for providing a quantitative estimation of OA
      severity. The per cent HJS area difference correlated highly with the
      pathological JSMI values (r = -0.83, p<0.001). The implementation of the JSMI
      based classification rules resulted in high classification accuracies for
      characterizing hips as normal or osteoarthritic, 90.6% (95% exact confidence
      interval (CI): 80.7-96.5%), as well as for discriminating among OA severity
      categories, 91.7% (95% CI: 77.5-98.2%). Additionally, a simplified approach of
      JSMI calculation is suggested for daily clinical use. These JSMI values (JSMI
      simplified) were found not to differ significantly from (p>0.05), and to be
      strongly correlated with (r = 0.96, p<0.001), the corresponding ones obtained by
      the computerized approach. Additionally, the implementation of classification
      rules based on JSMI simplified resulted in classification accuracies identical to
      the corresponding ones obtained for the JSMI-based rules. The proposed method may
      be utilized for evaluating OA and monitoring OA progression.

PMID- 18070827
TI  - Haemodynamic parameters of the hepatic artery and vein can detect liver
      metastases: assessment using contrast-enhanced ultrasound.
AB  - This study was to assess the changes in the haemodynamic parameters of the
      hepatic artery and vein in the diagnosis of liver metastases by contrast-enhanced
      ultrasound (CEUS). 52 patients with proven liver metastases (patient group) and
      23 normal volunteers (control group) were recruited in this study. Each subject
      was administered an intravenous bolus injection of SonoVue (0.6 ml). The arrival
      time in the hepatic artery (AT HA), time to peak in the hepatic artery (TTP HA),
      peak intensity of the hepatic artery (PI HA), arrival time in the hepatic vein
      (AT HV), time to peak in the hepatic vein (TTP HV) and peak intensity of the
      hepatic vein (PI HV) were measured with the use of time-intensity curve software.
      The hepatic artery to vein transit time (HAVTT) was calculated as the difference
      between the arrival times in the hepatic artery and the hepatic vein. AT HA, TTP
      HA, AT HV, TTP HV and HAVTT in the patient group were significantly shorter than
      those of the control group (P<0.01). PI HA and PI HV in the patient group were
      significantly higher than those of the control group (P<0.01). These results
      suggest that CEUS assessment of changes in the haemodynamic parameters of the
      hepatic artery and vein help to diagnose liver metastases. This functional
      imaging technique may contribute to the early detection of micrometastases in the
      liver.

PMID- 18070828
TI  - Biologically effective dose using reciprocal repair for varying fraction doses
      and fraction intervals.
AB  - Hyperfractionated regimes are being used more frequently; this has created a
      clinical need for more sophisticated biologically effective dose (BED)
      calculations. A formula is given for calculating BED assuming reciprocal repair
      in the case of changing dose per fraction and changing interfraction interval.
      Example applications are given for hyperfractionated schedules. It is shown that
      the formula is useful for calculating isoeffective schedules for a treatment with
      unplanned gaps and for comparing regimes in trial design. This work should be of
      value for comparing risk across accelerated schedules when an organ of the
      central nervous system is at risk. Uncertainties in choice of parameter and model
      are discussed: the bi-exponential model of repair is invoked for this purpose.

PMID- 18070830
TI  - Metabolic consequences and therapeutic options in highly active antiretroviral
      therapy in human immunodeficiency virus-1 infection.
AB  - The use of highly active antiretroviral therapy (HAART) in HIV-1 infection
      confers immunological and survival advantages, at the cost of induction of
      significant metabolic disturbances. These include insulin resistance,
      disturbances in lipid metabolism, glucose homeostasis, adipocyte physiology and
      body fat partitioning with peripheral lipoatrophy and visceral obesity. These
      metabolic disturbances produce clinical manifestations which impact on the future
      health of the HIV-infected patient, including hyperlipidaemia, lipodystrophy,
      metabolic syndrome, cardiovascular disease and type 2 diabetes. These conditions
      are evident in the relative short term as HAART (and possibly HIV infection)
      appears to accelerate their pathogenesis. The current understanding of the
      mechanisms and time courses for developing metabolic complications on HAART is
      reviewed in this paper. The efficacy of therapeutic interventions for insulin
      resistance, hyperlipidaemia, body fat partitioning disorders and metabolic
      syndrome is summarized.

PMID- 18070829
TI  - The role of thrombophilia and thyroid autoimmunity in unexplained infertility,
      implantation failure and recurrent spontaneous abortion.
AB  - BACKGROUND: The role of thrombophilia and thyroid autoimmunity in unexplained
      infertility (UI), implantation failure (IF) and recurrent spontaneous abortion
      (RSA) is controversial and poorly understood. METHODS: From March, 2004 to
      January, 2007, 119 women were prospectively included: 32 oocyte donors, 31
      patients with UI, 26 with IF and 30 with RSA. The IF and RSA groups presented
      normal preimplantation genetic screening. Protein C, protein S, antithrombin III,
      lupus anticoagulant, activated protein C resistance (APCR), immunoglobulin M and
      G anticardiolipin antibodies, homocystine, Factor V Leiden, prothrombin G20210A
      mutation, methylentetrahydrofolate reductase C677T mutation, thyroid-stimulating
      hormone (TSH), free thyroxine, anti-thyroid peroxidase (TPO) and anti
      thyroglobulin (TG) antibodies were assessed. RESULTS: The prevalence of
      thrombophilia was high and similar among groups. In the IF group, the prevalence
      of APCR (15.4%), lupus anticoagulant (11.5%) and combined thrombophilia (19.2%)
      was higher, but not significantly different, than the other three groups. The
      prevalence of thyroid autoimmunity in women with IF (anti-TPO antibodies, P =
      0.009; anti-TPO plus anti-TG antibodies,P = 0.04) and UI (anti-TPO, P = 0.002;
      anti-TG, P = 0.019; anti-TPO plus anti-TG antibodies, P = 0.005) was
      significantly increased in comparison to those with RSA. There was also a trend
      towards a higher prevalence of thyroid autoimmunity in the UI and IF groups than
      in the control group. TSH and free thyroxine levels all remained within a normal
      range. CONCLUSIONS: When embryo aneuploidy is ruled out, thrombophilia could
      constitute an etiologic factor in IF. Furthermore, thyroid autoimmunity is
      strongly related to UI and IF.

PMID- 18070831
TI  - Continuous versus intermittent infusion of temocillin, a directed spectrum
      penicillin for intensive care patients with nosocomial pneumonia: stability,
      compatibility, population pharmacokinetic studies and breakpoint selection.
AB  - BACKGROUND AND AIMS: Temocillin, a 6alpha-methoxy-penicillin stable towards most
      beta-lactamases (including extended-spectrum beta-lactamase), is presented as an
      alternative to carbapenems for susceptible Enterobacteriaceae in microbiological
      surveys. We aimed at documenting its potential clinical usefulness in intensive
      care (IC) patients using pharmacokinetic/pharmacodynamic approaches applied to
      conventional (twice daily) and continuous infusion (CI) modes of administration.
      METHODS: (i) In vitro evaluation of temocillin stability and compatibility with
      other drugs under conditions pertinent of CI in IC patients; (ii) pharmacokinetic
      study in patients treated by CI (4 g/day; n = 6) versus [twice daily (2 g every
      12 h); n = 6]; (iii) population pharmacokinetic analysis of twice daily with
      Monte Carlo simulations to determine 95% probability of target attainment
      (PTA(95)) versus MIC (based on time above MIC > or = 40% for measured free drug).
      RESULTS: Temocillin was stable at 37 degrees C in 8.34% solutions for 24 h and
      compatible with flucloxacillin and aminoglycosides, but not with several other
      antibiotic and non-antibiotic drugs. With CI, stable total serum concentrations
      were 73.5 +/- 3.0 mg/L (SEM) and free concentration 29.3 +/- 2.8 mg/L. With twice
      daily, Cmax (total drug) was 147 +/- 12.3 mg/L (SEM; free drug: 50.3 +/- 15.8
      mg/L), lowest trough (total drug) 12.3 mg/L, and PTA(95) (free drug) obtained for
      MIC < or = 8 mg/L. CONCLUSIONS: Temocillin (4 g/day) by CI yields stable free
      serum concentrations above the current breakpoint (16 mg/L), although individual
      variations may suggest lowering the breakpoint to 8 mg/L (as for twice daily)
      unless the daily dose or the frequency of administration is increased.

PMID- 18070832
TI  - Broad-spectrum in vitro antibacterial activities of clay minerals against
      antibiotic-susceptible and antibiotic-resistant bacterial pathogens.
AB  - OBJECTIVES: The capacity to properly address the worldwide incidence of
      infectious diseases lies in the ability to detect, prevent and effectively treat
      these infections. Therefore, identifying and analysing inhibitory agents are
      worthwhile endeavours in an era when few new classes of effective antimicrobials
      have been developed. The use of geological nanomaterials to heal skin infections
      has been evident since the earliest recorded history, and specific clay minerals
      may prove valuable in the treatment of bacterial diseases, including infections
      for which there are no effective antibiotics, such as Buruli ulcer and multidrug
      resistant infections. METHODS: We have subjected two iron-rich clay minerals,
      which have previously been used to treat Buruli ulcer patients, to broth culture
      testing of antibiotic-susceptible and antibiotic-resistant pathogenic bacteria to
      assess the feasibility of using clay minerals as therapeutic agents. RESULTS: One
      specific mineral, CsAg02, demonstrated bactericidal activity against pathogenic
      Escherichia coli, extended-spectrum beta-lactamase (ESBL) E. coli, Salmonella
      enterica serovar Typhimurium, Pseudomonas aeruginosa and Mycobacterium marinum,
      and a combined bacteriostatic/bactericidal effect against Staphylococcus aureus,
      penicillin-resistant S. aureus, methicillin-resistant S. aureus (MRSA) and
      Mycobacterium smegmatis, whereas another mineral with similar structure and bulk
      crystal chemistry, CsAr02, had no effect on or enhanced bacterial growth. The
      <0.2 microm fraction of CsAg02 and CsAg02 heated to 200 or 550 degrees C retained
      bactericidal activity, whereas cation-exchanged CsAg02 and CsAg02 heated to 900
      degrees C no longer killed E. coli. CONCLUSIONS: Our results indicate that
      specific mineral products have intrinsic, heat-stable antibacterial properties,
      which could provide an inexpensive treatment against numerous human bacterial
      infections.

PMID- 18070833
TI  - Sleeping well, aging well: a descriptive and cross-sectional study of sleep in
      "successful agers" 75 and older.
AB  - OBJECTIVES: To examine diary-based, laboratory-based, and actigraphic measures of
      sleep in a group of healthy older women and men (> or =75 years of age) without
      sleep/wake complaints and to describe sleep characteristics which may be
      correlates of health-related quality of life in old age. DESIGN: Cross-sectional,
      descriptive study. SETTING: University-based sleep and chronobiology program.
      INTERVENTION: None. PARTICIPANTS: Sixty-four older adults (30 women, 34 men; mean
      age 79). MEASUREMENTS: We used diary-, actigraphic-, and laboratory-based
      measures of sleep, health-related quality of life, mental health, social support,
      and coping strategies. We used two-group t-tests to compare baseline demographic
      and clinical measures between men and women, followed by ANOVA on selected EEG
      measures to examine first-night effects as evidence of physiological
      adaptability. Finally, we examined correlations between measure of sleep and
      health-related quality of life. RESULTS: We observed that healthy men and women
      aged 75 and older can experience satisfactory nocturnal sleep quality and daytime
      alertness, especially as reflected in self-report and diary-based measures.
      Polysomnography (psg) suggested the presence of a first-night effect, especially
      in men, consistent with continued normal adaptability in this cohort of healthy
      older adults. Continuity and depth of sleep in older women were superior to that
      of men. Diary-based measures of sleep quality (but not psg measures) correlated
      positively (small to moderate effect sizes) with physical and mental health
      related quality of life. CONCLUSIONS: Sleep quality and daytime alertness in late
      life may be more important aspects of successful aging than previously
      appreciated. Good sleep may be a marker of good functioning across a variety of
      domains in old age. Our observations suggest the need to study interventions
      which protect sleep quality in older adults to determine if doing so fosters
      continued successful aging.

PMID- 18070834
TI  - Personal and societal construction of illness among individuals with rapid
      cycling bipolar disorder: a life-trajectory perspective.
AB  - OBJECTIVE: Bipolar disorder is a chronic mental illness associated with
      substantial impairment in quality of life and function. Although there has been
      tremendous growth in understanding bipolar disorder with respect to treatments,
      very little study has focused on the viewpoint of affected individuals. The
      purpose of this study was to examine the subjective experience of illness among
      19 men and women with rapid cycling bipolar disorder receiving treatment at an
      academic psychiatry clinic. METHODS: Personal constructs of illness with respect
      to life-trajectory and societal reaction to the individual, specifically the
      issue of stigma, were evaluated using a semistructured, open-ended
      anthropological interview. RESULTS: Participants perceived bipolar disorder as a
      disease with biologic underpinnings. Stigma was a major issue for all
      individuals. In common with individuals without serious mental illness,
      individuals with bipolar disorder work at mastering developmental tasks
      appropriate for their life stage. At times, younger individuals appeared to have
      difficulty separating their own identity from the effects of illness. For older
      individuals with bipolar disorder, life was perceived to be disrupted by bipolar
      disorder, with early plans and dreams often "derailed." CONCLUSION: Although
      bipolar disorder may severely alter an individual's planned life trajectory,
      accomplishment of life goals can at least partially offset the sense of loss that
      is often seen in bipolar illness.

PMID- 18070835
TI  - Impact of endocrine disruptor chemicals in gynaecology.
AB  - The potential hazardous effects that estrogen- and androgen-like chemicals may
      have both on wildlife and human health have attracted much attention from the
      scientific community. Endocrine disruptors (EDCs) are chemicals that have the
      capacity to interfere with normal signalling systems. EDCs may mimic, block or
      modulate the synthesis, release, transport, metabolism and binding or elimination
      of natural hormones. Even though potential EDCs may be present in the environment
      at only very low levels, they may still cause harmful effects, especially when
      several different compounds act on one target. EDCs include persistent
      pollutants, agrochemicals and widespread industrial compounds. Not all EDCs are
      man-made compounds; many plants produce substances (phytoestrogens) that can have
      different endocrine effects either adverse or beneficial in certain
      circumstances. Natural substances such as sex hormones from urban or farm wastes
      can become concentrated in industrial, agricultural and urban areas; thus, such
      wastes may be considered potential 'EDCs' for humans and/or wildlife. Much
      attention has focussed on changing trends in male reproductive parameters in
      relation to EDC exposure; however, studies on the female reproductive system have
      been less comprehensive. We have focussed this article on four major aspects of
      female reproductive health: fertility and fecundability, endometriosis,
      precocious puberty and breast and endometrial cancer.

PMID- 18070837
TI  - Functional anatomy of humor: positive affect and chronic mental illness.

PMID- 18070838
TI  - The neuroendocrine effects of traumatic brain injury.
AB  - Neuroendocrine dysfunction after traumatic brain injury (TBI) is under-diagnosed,
      under-treated, and may adversely affect the rate of recovery. Single or multiple
      pituitary-target hormone disruption occurs in up to two-thirds of persons with
      TBI, most commonly affecting the gonadal and growth hormone axes. The time course
      of decline in and recovery of pituitary function in relation to cognitive
      dysfunction and rehabilitation progress are not well described. This article
      reviews the clinical spectrum of neuroendocrine deficits after TBI and their
      underlying mechanisms. Future studies of the effects of hormonal replacement on
      recovery are recommended.

PMID- 18070839
TI  - Neurocognitive impairment and dementia in mood disorders.
AB  - In a substantial percentage of patients, mood disorders are accompanied by
      persistent neurocognitive impairment. Elderly patients with dementia often suffer
      from depression. Neurocognitive tests and imaging are increasingly used to
      complement diagnostics. Tests assessing memory, attention, executive functions,
      and visuospatial abilities might help to distinguish mood disorder patients who
      can be expected to develop dementia from those who will not. This review presents
      a summary of knowledge on neurocognitive profiles differentiating impairment in
      mood disorders and dementia. Ideas on pathophysiological causation and
      progression are translated into recommendations for patient management.

PMID- 18070840
TI  - Frontal white matter integrity in borderline personality disorder with self
      injurious behavior.
AB  - Self-injurious behavior in borderline personality disorder is a frequent cause of
      morbidity and mortality, but neurobiological studies examining this behavior are
      few. Nine women with borderline personality disorder self-injurious behavior and
      seven comparison subjects underwent diffusion tensor imaging (DTI). Trace and
      fractional anisotropy (FA) were calculated for frontal and posterior regions.
      Borderline personality disorder-self-injurious behavior subjects also underwent a
      battery of neuropsychological tests that emphasized executive functions. They had
      significantly higher trace and lower FA in inferior frontal but not posterior
      regions. Correlational analyses between DTI and cognitive variables showed a
      pattern of results that was contrary to expectations with posterior white matter
      integrity correlating with isolated measures of executive function and anterior
      white matter integrity correlating with a component of verbal memory test
      performance. Women with borderline personality disorder-self-injurious behavior
      exhibit decreased white matter microstructural integrity in inferior frontal
      brain regions that may include components of orbito-frontal circuitry.

PMID- 18070841
TI  - Methodological issues in conducting treatment trials for psychological
      nonepileptic seizures.
AB  - A randomized, placebo-controlled trial has yet to be completed in patients with
      psychological nonepileptic seizures (NES). Treatment publications for NES are
      limited to class III trials and class IV reports. Little is written on the
      methodology of treatment trials in NES. The authors describe the procedures and
      limitations of such a trial to inform future NES treatment trials, based on their
      prospective, open-label pharmacological, feasibility trial. The authors review
      the recruitment, enrollment, completion of surveys, compliance, and follow-up of
      patients with NES. The majority of patients who enrolled, readily completed
      surveys and took the medication during the trial. Twelve patients were screened,
      eight enrolled, and six completed the trial. The authors discuss the use of
      outcomes and the various symptoms scales in the trial. A comprehensive
      neuropsychiatric initial assessment and assessing cognitive, emotional,
      behavioral, and psychosocial measures are important for monitoring the outcomes
      in NES treatment RCTs.

PMID- 18070842
TI  - Risk factors for and correlates of poststroke depression following
      discontinuation of antidepressants.
AB  - The authors randomly assigned nondepressed patients at least 3 months poststroke
      to receive nortriptyline, fluoxetine, or placebo for 3 months using double-blind
      methodology. Patients were followed at 3, 6, 9, and 21 months for new onset of
      depression. In patients treated with antidepressants, lesion volume and degree of
      social impairment were associated with subsequent late-onset of poststroke
      depression at 6 and 9 months. In the placebo group, severity of impairment in
      activities of daily living, at 3 and 9 months, was associated with late onset
      poststroke depression. Differences in the clinical/pathological correlates may
      reflect subtle differences in the pathophysiology of poststroke depression
      following prophylactic antidepressants.

PMID- 18070843
TI  - Review of adjunctive glutamate antagonist therapy in the treatment of catatonic
      syndromes.
AB  - Catatonia is a common neuropsychiatric syndrome which may arise from GABA-A
      hypoactivity, dopamine (D2) hypoactivity,and possibly glutamate NMDA
      hyperactivity. Amantadine and memantine have been reported as effective
      treatments for catatonia in selected cases, and probably mediate the presence of
      catatonic signs and symptoms through complex pathways involving glutamate
      antagonism. The authors identified 25 cases of catatonia treated with either
      agent. This article provides indirect evidence that glutamate antagonists may
      improve catatonic signs in some patients who fail to respond to established
      treatment, including lorazepam or electroconvulsive therapy. Further study of
      glutamate antagonists in the treatment of catatonia is needed.

PMID- 18070844
TI  - Hypocretin/Orexin: a molecular link between sleep, energy regulation, and
      pleasure.
AB  - Hypocretin (Hcrt) is a neurotransmitter of the dorsal and lateral hypothalamus
      that regulates sleep, appetite, and energy consumption. Recent evidence indicates
      that it is also involved in pleasure/reward-seeking. Mutation of the Hcrt
      receptor gene causes narcolepsy in canines, and Hcrt knockout mice exhibit
      narcolepsy-like symptoms. Human narcoleptics do not commonly have mutations in
      the ligand or receptor but do have degeneration of Hcrt-containing neurons,
      possibly through an autoimmune mechanism. When Hcrt neurons degenerate in mice,
      hypophagia and obesity are observed, symptoms that are also present in some human
      narcoleptics. This article reviews the recent literature with regard to the many
      functions of this single molecule. The authors suggest that eating habits and
      impulsivity may be topics worth exploring in the evaluation of narcoleptic
      patients.

PMID- 18070845
TI  - Neurological soft signs in mentally disordered offenders.
AB  - The study used the Neurological Evaluation Scale to assess neurological soft
      signs in 351 offenders and 80 healthy comparison subjects. Offenders were also
      interviewed using the Structured Clinical Interview for DSM-IV and the Hare
      Psychopathy Checklist. Neurological signs were significantly increased in
      offenders compared with healthy subjects. Offenders with repeated misdemeanors
      had higher rates of neurological signs than those with a single felony.
      Neurological scores were significantly predicted by lifetime diagnoses of
      psychotic, anxiety, and substance use disorders. Each diagnostic category was
      associated with a distinct pattern of neurological abnormalities.

PMID- 18070846
TI  - Does the presentation of Creutzfeldt-Jakob disease vary by age or presumed
      etiology? A meta-analysis of the past 10 years.
AB  - It is not clear whether differences in symptom presentation vary by age or
      etiological subtype in Creutzfeldt-Jakob disease. A PubMed search was conducted
      using the keyword "Creutzfeldt-Jakob" and results within the last 10 years were
      sorted by the English language. We found that certain characteristics, such as
      affective illness (28.8%), present more commonly in younger patients irrespective
      of disease type. Young age of onset predicts presenting symptoms of affective
      illness, sleep disturbance, and poor concentration, as well as certain
      neurological symptoms, including cerebellar/gait disturbance, visual/oculomotor
      disturbance, sensory disorder, vertigo/dizziness, and headache.

PMID- 18070847
TI  - Impaired perception of affective prosody in remitted patients with bipolar
      disorder.
AB  - Patients with bipolar disorder present deficits in facial emotion perception,
      both during a manic episode as well as upon recovery. Our goal in the present
      study was to investigate the ability of remitted patients with bipolar disorder
      to perceive affective prosody and to explore potential differences in the
      specific emotions that are troublesome for them. Participants included 19
      patients with bipolar disorder I, currently in remission, and 22 healthy
      comparison subjects, matched on age, education, and gender. An affective prosody
      test (APT) was administered to all participants. Bipolar patients had
      significantly lower overall scores on the APT than healthy individuals. This
      impairment was specific to female patients and certain emotions (e.g., fear and
      surprise).

PMID- 18070848
TI  - Psychopathology in verified Huntington's disease gene carriers.
AB  - Huntington's disease is characterized by motor, cognitive, and neuropsychiatric
      symptoms. This study reviews original research on psychopathology in Huntington's
      disease that uses standardized instruments in verified gene carriers. Frequently
      reported neuropsychiatric symptoms are depressed mood, anxiety, irritability, and
      apathy, with prevalences of 33% to 76%. Obsessive-compulsive symptoms and
      psychosis occur less often with prevalences of 10% to 52% and 3% to 11%,
      respectively. Available research provides little insight into the true
      prevalences of psychopathology in Huntington's disease due to small sample sizes,
      use of different methodologies, and lack of comparison groups. Future research
      requires larger cohorts stratified to disease stage, consistent methodologies,
      and adequate comparison groups.

PMID- 18070849
TI  - Mood-elevating effects of opioid analgesics in patients with bipolar disorder.
AB  - Opioids can have mood-elevating effects in healthy subjects and have been used
      successfully to treat refractory depressed patients. A few case reports indicate
      that opioid analgesics can induce mania. The authors investigated the mood
      reaction of opioid analgesics in patients with bipolar disorder. Nine (27%) of 33
      patients who took opioid analgesics for medical reasons experienced a significant
      hypomanic/manic reaction, and two other patients reported an antidepressant
      effect. None of the comparison subjects reported a significant mood reaction from
      opioid analgesics. These results indicate that opioid analgesics can have an
      important mood-altering effect on patients with known bipolar disorder.

PMID- 18070850
TI  - Electrode placement and ictal EEG indices in electroconvulsive therapy.
AB  - The authors determine whether quantitative electroencephalography (EEG) indices
      in electroconvulsive therapy (ECT) seizures correlate with stimulus electrode
      placement. The authors analyzed data from ECT seizures involving three electrode
      placements on 37 different quantitative EEG measures. Though there were a few
      statistically significant comparisons, no consistent pattern of differences was
      discerned among the three electrode placements. Though many different EEG
      analytical indices are available on modern ECT machines, the clinical or
      neurophysiologic relevance has yet to be established. These data provide a
      groundwork for future research on the neurophysiological aspects of ECT.

PMID- 18070851
TI  - Within-session mood changes from TMS in depressed patients.

PMID- 18070852
TI  - Efficacy of adjuvant high frequency repetitive transcranial magnetic stimulation
      on negative and positive symptoms of schizophrenia: preliminary results of a
      double-blind sham-controlled study.
AB  - The potential effect of repetitive transcranial magnetic stimulation (rTMS) on
      core positive and negative symptoms in schizophrenia has not yet been clearly
      established. The aim of this study was to examine the efficacy of adjuvant 10 Hz,
      suprathreshold left prefrontal rTMS in negative symptoms of schizophrenia in a
      double-blind sham-controlled design. Additionally, our study also investigated
      the suitability of applying the same stimulus condition on positive symptoms. Ten
      right-handed schizophrenia patients received sham or active 10 Hz suprathreshold
      rTMS to the left dorsolateral prefrontal cortex with psychopathology, depression
      and global improvement ratings before and after rTMS sessions. Compared to sham,
      active rTMS significantly improved negative symptoms, irrespective of change in
      depressive symptoms.

PMID- 18070853
TI  - Phenomenological distinctions needed in DSM-V: delirium, subsyndromal delirium,
      and dementias.

PMID- 18070854
TI  - Cilostazol, a cAMP phosphodiesterase 3 inhibitor, in the treatment of poststroke
      depression.

PMID- 18070855
TI  - Basal Ganglia calcification and pulmonary embolism in catatonia.

PMID- 18070856
TI  - Potential drugs for improving chronic fatigue syndrome.

PMID- 18070857
TI  - Pathological gambling associated with cabergoline therapy in a patient with a
      pituitary prolactinoma.

PMID- 18070859
TI  - Neuroanatomical changes after eye movement desensitization and reprocessing
      (EMDR) treatment in posttraumatic stress disorder.

PMID- 18070858
TI  - Acquired variant of Rett's disorder and response to lamotrigine.

PMID- 18070860
TI  - A case report with ziprasidone-induced catatonic symptoms.

PMID- 18070861
TI  - Possible neuroleptic malignant syndrome associated with paliperidone.

PMID- 18070862
TI  - Differential cerebral cortical responsiveness examination in minimally conscious
      versus persistent vegetative states: a new role for neuropsychiatry and
      behavioral neurology.

PMID- 18070863
TI  - The schizophrenic disguise of complex partial seizures.

PMID- 18070864
TI  - Amantadine in catatonia due to major depressive disorder in a medically ill
      patient.

PMID- 18070865
TI  - Worsened agitation and confusion in schizophrenia subsequent to high-dose
      aripiprazole.

PMID- 18070866
TI  - MELAS presented with status epilepticus and Anton-Babinski syndrome; value of ADC
      mapping in MELAS.

PMID- 18070867
TI  - Acute hypertensive crisis may be a risk factor for Alzheimer's disease induction
      and progression.

PMID- 18070868
TI  - Olanzapine-induced tardive dystonia successfully treated by tetrabenazine.

PMID- 18070869
TI  - GABA(A) versus GABA(B) in catatonia.

PMID- 18070870
TI  - A case of frontotemporal lobar degeneration (FTLD) with panic attack as the first
      symptom.

PMID- 18070871
TI  - A case of late-onset obsessive compulsive disorder developing frontotemporal
      lobar degeneration.

PMID- 18070872
TI  - Amisulpride-induced neuroleptic malignant syndrome.

PMID- 18070873
TI  - New-onset paranoia and bipolar disorder associated with intracranial aneurysm.

PMID- 18070874
TI  - A 49-kDa mini-lipoxygenase from Anabaena sp. PCC 7120 retains catalytically
      complete functionality.
AB  - Anabaena sp. PCC 7120 is one of the few prokaryotes harboring a lipoxygenase
      (LOX) gene. The sequence resides in an open reading frame encoding a fusion
      protein of a catalase-like hemoprotein with an unusually short LOX (approximately
      49 kDa) at the C terminus. The recombinant mini-LOX contains a non-heme iron in
      the active site and is highly active with linoleic and alpha-linolenic acids
      (which occur naturally in Anabaena) giving the respective 9R-hydroperoxides, the
      mirror image of the 9S-LOX products of plants. Using stereospecifically labeled
      [11-(3)H]linoleic acids we show that reaction is catalyzed via a typical
      antarafacial relationship of initial hydrogen abstraction and oxygenation. The
      mini-LOX oxygenated C16/C18:2-phosphatidylcholine with 9R specificity, suggesting
      a "tail first" mode of fatty acid binding. Site-directed mutagenesis of an active
      site Ala (Ala215), typically conserved as Gly in R-LOX, revealed that
      substitution with Gly retained 9R specificity, whereas the larger Val
      substitution switched oxygenation to 13S, implying that Ala215 represents the
      functional equivalent of the Gly in other R-LOX. Metabolism studies using a
      synthetic fatty acid with extended double bond conjugation, 9E,11Z,14Z
      20:3omega6, showed that the mini-LOX can control oxygenation two positions
      further along the fatty acid carbon chain. We conclude that the mini-LOX, despite
      lacking the beta-barrel domain and much additional sequence, is catalytically
      complete. Interestingly, animal and plant LOX, which undoubtedly share a common
      ancestor, are related in sequence only in the catalytic domain; it is possible
      that the prokaryotic LOX represents a common link and that the beta-barrel domain
      was then acquired independently in the animal and plant kingdoms.

PMID- 18070875
TI  - Malin decreases glycogen accumulation by promoting the degradation of protein
      targeting to glycogen (PTG).
AB  - Lafora disease (LD) is an autosomal recessive neurodegenerative disease that
      results in progressive myoclonus epilepsy and death. LD is caused by mutations in
      either the E3 ubiquitin ligase malin or the dual specificity phosphatase laforin.
      A hallmark of LD is the accumulation of insoluble glycogen in the cytoplasm of
      cells from most tissues. Glycogen metabolism is regulated by phosphorylation of
      key metabolic enzymes. One regulator of this phosphorylation is protein targeting
      to glycogen (PTG/R5), a scaffold protein that binds both glycogen and many of the
      enzymes involved in glycogen synthesis, including protein phosphatase 1 (PP1),
      glycogen synthase, phosphorylase, and laforin. Overexpression of PTG markedly
      increases glycogen accumulation, and decreased PTG expression decreases glycogen
      stores. To investigate if malin and laforin play a role in glycogen metabolism,
      we overexpressed PTG, malin, and laforin in tissue culture cells. We found that
      expression of malin or laforin decreased PTG-stimulated glycogen accumulation by
      25%, and co-expression of malin and laforin abolished PTG-stimulated glycogen
      accumulation. Consistent with this result, we found that malin ubiquitinates PTG
      in a laforin-dependent manner, both in vivo and in vitro, and targets PTG for
      proteasome-dependent degradation. These results suggest an additional mechanism,
      involving laforin and malin, in regulating glycogen metabolism.

PMID- 18070876
TI  - Interactions between the photosystem II subunit PsbS and xanthophylls studied in
      vivo and in vitro.
AB  - The photosystem II subunit PsbS is essential for excess energy dissipation (qE);
      however, both lutein and zeaxanthin are needed for its full activation. Based on
      previous work, two models can be proposed in which PsbS is either 1) the gene
      product where the quenching activity is located or 2) a proton-sensing trigger
      that activates the quencher molecules. The first hypothesis requires xanthophyll
      binding to two PsbS-binding sites, each activated by the protonation of a
      dicyclohexylcarbodiimide-binding lumen-exposed glutamic acid residue. To assess
      the existence and properties of these xanthophyll-binding sites, PsbS point
      mutants on each of the two Glu residues PsbS E122Q and PsbS E226Q were crossed
      with the npq1/npq4 and lut2/npq4 mutants lacking zeaxanthin and lutein,
      respectively. Double mutants E122Q/npq1 and E226Q/npq1 had no qE, whereas
      E122Q/lut2 and E226Q/lut2 showed a strong qE reduction with respect to both lut2
      and single glutamate mutants. These findings exclude a specific interaction
      between lutein or zeaxanthin and a dicyclohexylcarbodiimide-binding site and
      suggest that the dependence of nonphotochemical quenching on xanthophyll
      composition is not due to pigment binding to PsbS. To verify, in vitro, the
      capacity of xanthophylls to bind PsbS, we have produced recombinant PsbS refolded
      with purified pigments and shown that Raman signals, previously attributed to
      PsbS-zeaxanthin interactions, are in fact due to xanthophyll aggregation. We
      conclude that the xanthophyll dependence of qE is not due to PsbS but to other
      pigment-binding proteins, probably of the Lhcb type.

PMID- 18070877
TI  - PagP activation in the outer membrane triggers R3 core oligosaccharide truncation
      in the cytoplasm of Escherichia coli O157:H7.
AB  - The Escherichia coli outer membrane phospholipid:lipid A palmitoyltransferase
      PagP is normally a latent enzyme, but it can be directly activated in outer
      membranes by lipid redistribution associated with a breach in the permeability
      barrier. We now demonstrate that a lipid A myristate deficiency in an E. coli
      O157:H7 msbB mutant constitutively activates PagP in outer membranes. The lipid A
      myristate deficiency is associated with hydrophobic antibiotic sensitivity and,
      unexpectedly, with serum sensitivity, which resulted from O-antigen
      polysaccharide absence due to a cytoplasmically determined truncation at the
      first outer core glucose unit of the R3 core oligosaccharide. Mutational
      inactivation of pagP in the myristate-deficient lipid A background aggravated the
      hydrophobic antibiotic sensitivity as a result of losing a partially compensatory
      increase in lipid A palmitoylation while simultaneously restoring serum
      resistance and O-antigen attachment to intact lipopolysaccharide. Complementation
      with either wild-type pagP or catalytically inactive pagPSer77Ala alleles
      restored the R3 core truncation. However, the intact lipopolysaccharide was
      preserved after complementation with an internal deletion pagPDelta5-14 allele,
      which mostly eliminates a periplasmic amphipathic alpha-helical domain but fully
      supports cell surface lipid A palmitoylation. Our findings indicate that
      activation of PagP not only triggers lipid A palmitoylation in the outer membrane
      but also separately truncates the R3 core oligosaccharide in the cytoplasm. We
      discuss the implication that PagP might function as an apical sensory transducer,
      which can be activated by a breach in the outer membrane permeability barrier.

PMID- 18070878
TI  - Direct spectroscopic study of reconstituted transcription complexes reveals that
      intrinsic termination is driven primarily by thermodynamic destabilization of the
      nucleic acid framework.
AB  - Changes in near UV circular dichroism (CD) and fluorescence spectra of site
      specifically placed pairs of 2-aminopurine residues have been used to probe the
      roles of the RNA hairpin and the RNA-DNA hybrid in controlling intrinsic
      termination of transcription. Functional transcription complexes were assembled
      directly by mixing preformed nucleic acid scaffolds of defined sequence with T7
      RNA polymerase (RNAP). Scaffolds containing RNA hairpins immediately upstream of
      a GC-rich hybrid formed complexes of reduced stability, whereas the same hairpins
      adjacent to a hybrid of rU-dA base pairs triggered complex dissociation and
      transcript release. 2-Aminopurine probes at the upstream ends of the hairpin
      stems show that the hairpins open on RNAP binding and that stem re-formation
      begins after one or two RNA bases on the downstream side of the stem have emerged
      from the RNAP exit tunnel. Hairpins directly adjacent to the RNA-DNA hybrid
      weaken RNAP binding, decrease elongation efficiency, and disrupt the upstream end
      of the hybrid as well as interfere with the movement of the template base at the
      RNAP active site. Probing the edges of the DNA transcription bubble demonstrates
      that termination hairpins prevent translocation of the RNAP, suggesting that they
      transiently "lock" the polymerase to the nucleic acid scaffold and, thus, hold
      the RNA-DNA hybrid "in frame." At intrinsic terminators the weak rU-dA hybrid and
      the adjacent termination hairpin combine to destabilize the elongation complex
      sufficiently to permit significant transcript release, whereas hairpin-dependent
      pausing provides time for the process to go to completion.

PMID- 18070879
TI  - cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated
      fatty acids.
AB  - The effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) on adipogenesis and
      obesity is controversial. Using in vitro cell culture models, we show that n-6
      PUFAs was pro-adipogenic under conditions with base-line levels of cAMP, but anti
      adipogenic when the levels of cAMP were elevated. The anti-adipogenic action of n
      6 PUFAs was dependent on a cAMP-dependent protein kinase-mediated induction of
      cyclooxygenase expression and activity. We show that n-6 PUFAs were pro
      adipogenic when combined with a high carbohydrate diet, but non-adipogenic when
      combined with a high protein diet in mice. The high protein diet increased the
      glucagon/insulin ratio, leading to elevated cAMP-dependent signaling and
      induction of cyclooxygenase-mediated prostaglandin synthesis. Mice fed the high
      protein diet had a markedly lower feed efficiency than mice fed the high
      carbohydrate diet. Yet, oxygen consumption and apparent heat production were
      similar. Mice on a high protein diet had increased hepatic expression of PGC
      1alpha (peroxisome proliferator-activated receptor gamma coactivator 1alpha) and
      genes involved in energy-demanding processes like urea synthesis and
      gluconeogenesis. We conclude that cAMP signaling is pivotal in regulating the
      adipogenic effect of n-6 PUFAs and that diet-induced differences in cAMP levels
      may explain the ability of n-6 PUFAs to either enhance or counteract adipogenesis
      and obesity.

PMID- 18070880
TI  - Tyrosine phosphorylation of MyD88 adapter-like (Mal) is critical for signal
      transduction and blocked in endotoxin tolerance.
AB  - Toll-like receptor 4 (TLR4) recognition of lipopolysaccharide triggers
      signalosome assembly among TLR4, sorting (e.g. MyD88 adapter-like (Mal)) and
      signaling (e.g. MyD88) adapters, initiating recruitment and activation of
      kinases, activation of transcription factors, and production of inflammatory
      mediators. In this study we examined whether tyrosine phosphorylation of Mal
      regulates its interactions with TLR4, MyD88, interleukin-1 (IL-1) receptor
      associated kinase (IRAK)-2, and tumor necrosis factor receptor-associated factor
      (TRAF)-6 and is important for signaling. Overexpression of wild-type Mal in human
      embryonic kidney 293T cells induced its constitutive tyrosine phosphorylation and
      led to activation of p38, NF-kappaB, and IL-8 gene expression. Mutagenesis of Tyr
      86, Tyr-106, and Tyr-159 residues within the Toll-IL-1 receptor domain impaired
      Mal tyrosine phosphorylation, interactions with Bruton tyrosine kinase,
      phosphorylation of p38, and NF-kappaB activation. Lipopolysaccharide triggered
      tyrosine phosphorylation of endogenous Mal and initiated Mal-Bruton-tyrosine
      kinase interactions in 293/TLR4/MD-2 cells and human monocytes that were
      suppressed in endotoxin-tolerant cells. Compared with wild-type Mal, Y86A-, Y06A
      , and Y159A-Mal variants exhibited higher interactions with TLR4 and MyD88,
      whereas associations with IRAK-2 and TRAF-6 were not affected. Overexpression of
      Y86A- and Y106A-Mal in 293/TLR4/MD-2 cells exerted dominant-negative effects on
      TLR4-inducible p38 phosphorylation and NF-kappaB reporter activation to the
      extent comparable with P125H-Mal-mediated suppression. In contrast, tyrosine
      deficient Mal species did not affect NF-kappaB activation when signaling was
      initiated at the post-receptor level by overexpression of MyD88, IRAK-2, or TRAF
      6. Thus, tyrosine phosphorylation of Mal is required for adapter signaling,
      regulates Mal interactions with TLR4 and receptor signaling, and is inhibited in
      endotoxin tolerance.

PMID- 18070881
TI  - N terminus of calpain 1 is a mitochondrial targeting sequence.
AB  - The ubiquitous m- and mu-calpains are thought to be localized in the cytosolic
      compartment, as is their endogenous inhibitor calpastatin. Previously, mu-calpain
      was found to be enriched in mitochondrial fractions isolated from rat cerebral
      cortex and SH-SY5Y neuroblastoma cells, but the submitochondrial localization of
      mu-calpain was not determined. In the present study, submitochondrial
      fractionation and digitonin permeabilization studies indicated that both calpain
      1 and calpain small subunit 1, which together form mu-calpain, are present in the
      mitochondrial intermembrane space. The N terminus of calpain 1 contains an
      amphipathic alpha-helical domain, and is distinct from the N terminus of calpain
      2. Calpain 1, but not calpain 2, was imported into mitochondria. Removal of the N
      terminal 22 amino acids of calpain 1 blocked the mitochondrial calpain import,
      while addition of this N-terminal region to calpain 2 or green fluorescent
      protein enabled mitochondrial import. The N terminus of calpain 1 was not
      processed following mitochondrial import, but was removed by autolysis following
      calpain activation. Calpain small subunit 1 was not directly imported into
      mitochondria, but was imported in the presence of calpain 1. The presence of a
      mitochondrial targeting sequence in the N-terminal region of calpain 1 is
      consistent with the localization of mu-calpain to the mitochondrial intermembrane
      space and provides new insight into the possible functions of this cysteine
      protease.

PMID- 18070882
TI  - Rapid turnover of the mTOR complex 1 (mTORC1) repressor REDD1 and activation of
      mTORC1 signaling following inhibition of protein synthesis.
AB  - mTORC1 is a complex of proteins that includes the mammalian target of rapamycin
      (mTOR) and several regulatory proteins. It is activated by a variety of hormones
      (e.g. insulin) and nutrients (e.g. amino acids) that act to stimulate cell growth
      and proliferation and repressed by hormones (e.g. glucocorticoids) that act to
      reduce cell growth. Curiously, mTORC1 signaling is reported to be rapidly (e.g.
      within 1-2 h) activated by inhibitors of protein synthesis that act on either
      mRNA translation elongation or gene transcription. However, the basis for the
      mTORC1 activation has not been satisfactorily delineated. In the present study,
      mTORC1 signaling was found to be activated in response to inhibition of either
      the initiation or elongation phases of mRNA translation. Changes in mTORC1
      signaling were inversely proportional to alterations in the expression of the
      mTORC1 repressor, REDD1, but not the expression of TRB3 or TSC2. Moreover the
      cycloheximide-induced increase in mTORC1 signaling was significantly attenuated
      in cells lacking REDD1, showing that REDD1 plays an integral role in the
      response. Finally, the half-life of REDD1 was estimated to be 5 min or less.
      Overall, the results are consistent with a model in which inhibition of protein
      synthesis leads to a loss of REDD1 protein because of its rapid degradation, and
      in part reduced REDD1 expression subsequently leads to de-repression of mTORC1
      activity.

PMID- 18070883
TI  - A novel role of Sprouty 2 in regulating cellular apoptosis.
AB  - Sprouty (SPRY) proteins modulate receptor-tyrosine kinase signaling and, thereby,
      regulate cell migration and proliferation. Here, we have examined the role of
      endogenous human SPRY2 (hSPRY2) in the regulation of cellular apoptosis. Small
      inhibitory RNA-mediated silencing of hSPRY2 abolished the anti-apoptotic action
      of serum in adrenal cortex adenocarcinoma (SW13) cells. Silencing of hSPRY2
      decreased serum- or epidermal growth factor (EGF)-elicited activation of AKT and
      ERK1/2 and reduced the levels of EGF receptor. Silencing of hSPRY2 also inhibited
      serum-induced activation of p90RSK and decreased phosphorylation of pro-apoptotic
      protein BAD (BCL2-antagonist of cell death) by p90RSK. Inhibiting both the ERK1/2
      and AKT pathways abolished the ability of serum to protect against apoptosis,
      mimicking the effects of silencing hSPRY2. Serum transactivated the EGF receptor
      (EGFR), and inhibition of the EGFR by a neutralizing antibody attenuated the anti
      apoptotic actions of serum. Consistent with the role of EGFR and perhaps other
      growth factor receptors in the anti-apoptotic actions of serum, the tyrosine
      kinase binding domain of c-Cbl (Cbl-TKB) protected against down-regulation of the
      growth factor receptors such as EGFR and preserved the anti-apoptotic actions of
      serum when hSpry2 was silenced. Additionally, silencing of Spry2 in c-Cbl null
      cells did not alter the ability of serum to promote cell survival. Moreover,
      reintroduction of wild type hSPRY2, but not its mutants that do not bind c-Cbl or
      CIN85 into SW13 cells after endogenous hSPRY2 had been silenced, restored the
      anti-apoptotic actions of serum. Overall, we conclude that endogenous hSPRY2
      mediated regulation of apoptosis requires c-Cbl and is manifested by the ability
      of hSPRY2 to sequester c-Cbl and thereby augment signaling via growth factor
      receptors.

PMID- 18070884
TI  - Characterization of some molecular mechanisms governing autoactivation of the
      catalytic domain of the anaplastic lymphoma kinase.
AB  - NPM/ALK is an oncogenic fusion protein expressed in approximately 50% of
      anaplastic large cell lymphoma cases. It derives from the t(2;5)(p23;q35)
      chromosomal translocation that fuses the catalytic domain of the tyrosine kinase,
      anaplastic lymphoma kinase (ALK), with the dimerization domain of the
      ubiquitously expressed nucleophosmin (NPM) protein. Dimerization of the ALK
      kinase domain leads to its autophosphorylation and constitutive activation.
      Activated NPM/ALK stimulates downstream survival and proliferation signaling
      pathways leading to malignant transformation. Herein, we investigated the
      molecular mechanisms of autoactivation of the catalytic domain of ALK. Because
      kinases are typically regulated by autophosphorylation of their activation loops,
      we systematically mutated (Tyr --> Phe) three potential autophosphorylation sites
      contained in the "YXXXYY" motif of the ALK activation loop, and determined the
      effect of these mutations on the catalytic activity and biological function of
      NPM/ALK. We observed that mutation of both the second and third tyrosine residues
      (YFF mutant) did not affect the kinase activity or transforming ability of
      NPM/ALK. In contrast, mutation of the first and second (FFY), first and third
      (FYF), or all three (FFF) tyrosine residues impaired both kinase activity and
      transforming ability of NPM/ALK. Furthermore, a DFF mutant, in which the aspartic
      residue introduces a negative charge similar to a phosphorylated tyrosine,
      possessed catalytic activity similar to the YFF mutant. Together, our findings
      indicate that phosphorylation of the first tyrosine of the YXXXYY motif is
      necessary for the autoactivation of the ALK kinase domain and the transforming
      activity of NPM/ALK.

PMID- 18070885
TI  - Determination of the Escherichia coli S-nitrosoglutathione response network using
      integrated biochemical and systems analysis.
AB  - During infection or denitrification, bacteria encounter reactive nitrogen
      species. Although the molecular targets of and defensive response against nitric
      oxide (NO) in Escherichia coli are well studied, the response elements specific
      to S-nitrosothiols are less clear. Previously, we employed an integrated systems
      biology approach to unravel the E. coli NO-response network. Here we use a
      similar approach to confirm that S-nitrosoglutathione (GSNO) primarily impacts
      the metabolic and regulatory programs of E. coli in minimal medium by reaction
      with homocysteine and cysteine and subsequent disruption of the methionine
      biosynthesis pathway. Targeting of homocysteine and cysteine results in altered
      regulatory activity of MetJ, MetR, and CysB, activation of the stringent response
      and growth inhibition. Deletion of metJ or supplementation with methionine
      strongly attenuated the effect of GSNO on growth and gene expression.
      Furthermore, GSNO inhibited the ArcAB two-component system. Consistent with the
      underlying nitrosative and thiol-oxidative chemistry, growth inhibition and the
      majority of the regulatory perturbations were dependent upon GSNO internalization
      by the Dpp dipeptide transporter. Contrastingly, perturbation of NsrR appeared to
      be a result of the submicromolar levels of NO released from GSNO and did not
      require GSNO internalization.

PMID- 18070886
TI  - Activity of the Bcr GTPase-activating domain is regulated through direct
      protein/protein interaction with the Rho guanine nucleotide dissociation
      inhibitor.
AB  - The cycling of Rac GTPases, alternating between an active GTP- and an inactive
      GDP-bound state, is controlled by guanine nucleotide exchange factors, GTPase
      activating proteins (GAPs), and guanine nucleotide dissociation inhibitors
      (GDIs). Little is known about how these controlling activities are coordinated.
      Studies using null mutant mice have demonstrated that Bcr and Abr are two
      physiologically important GAPs for Rac. Here, we report that in the presence of
      RhoGDIalpha, Bcr is unable to convert Rac-GTP to Rac-GDP because RhoGDI forms a
      direct protein complex with Bcr. Interestingly, RhoGDIalpha binds to the GAP
      domain in Bcr and Abr, a domain that also binds to Rac-GTP and catalyzes
      conversion of the bound GTP to GDP on Rac. The presence of activated Rac
      diminished the Bcr/RhoGDIalpha interaction. Moreover, a Bcr mutant that lacks the
      ability to promote hydrolysis of Rac-GTP bound to its GAP domain did not bind to
      RhoGDIalpha in cell lysates, indicating that binding of RhoGDIalpha and Rac-GTP
      to the Bcr GAP domain is mutually exclusive. Our results provide the first
      identification of a protein that regulates BcrGAP activity.

PMID- 18070887
TI  - Phosphatidylinositol 3-kinase-dependent membrane recruitment of Rac-1 and p47phox
      is critical for alpha-platelet-derived growth factor receptor-induced production
      of reactive oxygen species.
AB  - Platelet-derived growth factor (PDGF) plays a critical role in the pathogenesis
      of proliferative diseases. NAD(P)H oxidase (Nox)-derived reactive oxygen species
      (ROS) are essential for signal transduction by growth factor receptors. Here we
      investigated the dependence of PDGF-AA-induced ROS production on the cytosolic
      Nox subunits Rac-1 and p47(phox), and we systematically evaluated the signal
      relay mechanisms by which the alphaPDGF receptor (alphaPDGFR) induces ROS
      liberation. Stimulation of the alphaPDGFR led to a time-dependent increase of
      intracellular ROS levels in fibroblasts. Pharmacological inhibitor experiments
      and enzyme activity assays disclosed Nox as the source of ROS. alphaPDGFR
      activation is rapidly followed by the translocation of p47(phox) and Rac-1 from
      the cytosol to the cell membrane. Experiments performed in p47(phox)(-/-) cells
      and inhibition of Rac-1 or overexpression of dominant-negative Rac revealed that
      these Nox subunits are required for PDGF-dependent Nox activation and ROS
      liberation. To evaluate the signaling pathway mediating PDGF-AA-dependent ROS
      production, we investigated Ph cells expressing mutant alphaPDGFRs that lack
      specific binding sites for alphaPDGFR-associated signaling molecules (Src,
      phosphatidylinositol 3-kinase (PI3K), phospholipase Cgamma, and SHP-2). Lack of
      PI3K signaling (but not Src, phospholipase Cgamma, or SHP-2) completely abolished
      PDGF-dependent p47(phox) and Rac-1 translocation, increase of Nox activity, and
      ROS production. Conversely, a mutant alphaPDGFR able to activate only PI3K was
      sufficient to mediate these subcellular events. Furthermore, the catalytic PI3K
      subunit p110alpha (but not p110beta) was identified as the crucial isoform that
      elicits alphaPDGFR-mediated production of ROS. Finally, bromodeoxyuridine
      incorporation and chemotaxis assays revealed that the lack of ROS liberation
      blunted PDGF-AA-dependent chemotaxis but not cell cycle progression. We conclude
      that PI3K/p110alpha mediates growth factor-dependent ROS production by recruiting
      p47(phox) and Rac-1 to the cell membrane, thereby assembling the active Nox
      complex. ROS are required for PDGF-AA-dependent chemotaxis but not proliferation.

PMID- 18070888
TI  - Monoubiquitylation of alpha-synuclein by seven in absentia homolog (SIAH)
      promotes its aggregation in dopaminergic cells.
AB  - alpha-Synuclein plays a major role in Parkinson disease. Unraveling the
      mechanisms of alpha-synuclein aggregation is essential to understand the
      formation of Lewy bodies and their involvement in dopaminergic cell death. alpha
      Synuclein is ubiquitylated in Lewy bodies, but the role of alpha-synuclein
      ubiquitylation has been mysterious. We now report that the ubiquitin-protein
      isopeptide ligase seven in absentia homolog (SIAH) directly interacts with and
      monoubiquitylates alpha-synuclein and promotes its aggregation in vitro and in
      vivo, which is toxic to cells. Mass spectrometry analysis demonstrates that SIAH
      monoubiquitylates alpha-synuclein at lysines 12, 21, and 23, which were
      previously shown to be ubiquitylated in Lewy bodies. SIAH ubiquitylates lysines
      10, 34, 43, and 96 as well. Suppression of SIAH expression by short hairpin RNA
      to SIAH-1 and SIAH-2 abolished alpha-synuclein monoubiquitylation in dopaminergic
      cells, indicating that endogenous SIAH ubiquitylates alpha-synuclein. Moreover,
      SIAH co-immunoprecipitated with alpha-synuclein from brain extracts. Inhibition
      of proteasomal, lysosomal, and autophagic pathways, as well as overexpression of
      a ubiquitin mutant less prone to deubiquitylation, G76A, increased
      monoubiquitylation of alpha-synuclein by SIAH. Monoubiquitylation increased the
      aggregation of alpha-synuclein in vitro. At the electron microscopy level,
      monoubiquitylated alpha-synuclein promoted the formation of massive amounts of
      amorphous aggregates. Monoubiquitylation also increased alpha-synuclein
      aggregation in vivo as observed by increased formation of alpha-synuclein
      inclusion bodies within dopaminergic cells. These inclusions are toxic to cells,
      and their formation was prevented when endogenous SIAH expression was suppressed.
      Our data suggest that monoubiquitylation represents a possible trigger event for
      alpha-synuclein aggregation and Lewy body formation.

PMID- 18070889
TI  - Streptococcus pneumoniae choline-binding protein E interaction with
      plasminogen/plasmin stimulates migration across the extracellular matrix.
AB  - The virulence mechanisms leading Streptococcus pneumoniae to convert from
      nasopharyngeal colonization to a tissue-invasive phenotype are still largely
      unknown. Proliferation of infection requires penetration of the extracellular
      matrix, which occurs by recruitment of host proteases to the bacterial cell
      surface. We present evidence supporting the role of choline-binding protein E
      (CBPE) (a member of the surface-exposed choline-binding protein family) as an
      important receptor for human plasminogen, the precursor of plasmin. The results
      of ligand overlay blot analyses, solid-phase binding assays, and surface plasmon
      resonance experiments support the idea of an interaction between CBPE and
      plasminogen. We have shown that the phosphorylcholine esterase (Pce) domain of
      CBPE interacts with the plasminogen kringle domains. Analysis of the crystal
      structure of the Pce domain, followed by site-directed mutagenesis, allowed the
      identification of the plasminogen-binding region composed in part by lysine
      residues, some of which map in a linear fashion on the surface of the Pce domain.
      The biological relevance of the CBPE-plasminogen interaction is supported by the
      fact that, compared to the wild-type strain, a mutant of pneumococcus with the
      cbpE gene deleted (i) displays a reduced level of plasminogen binding and plasmin
      activation and (ii) shows reduced ability to cross the extracellular matrix in an
      in vitro model. These results support the idea of a physiological role for the
      CBPE-plasminogen interaction in pneumococcal dissemination into human tissue.

PMID- 18070890
TI  - FcgammaRIII mediates immunoglobulin G-induced interleukin-10 and is required for
      chronic Leishmania mexicana lesions.
AB  - FcRgamma and interleukin-10 (IL-10) are both required for chronic disease in
      C57BL/6 mice with Leishmania mexicana parasite infection. FcRgamma is a component
      of several different FcRs and may be a component of some T-cell receptors. The
      initial antibody response to L. mexicana is an immunoglobulin G1 (IgG1) response,
      and IgG1 preferentially binds to FcgammaRIII in other systems. To begin to
      dissect the mechanisms by which FcgammaRs contribute to chronic disease, we
      infected FcgammaRIII knockout (KO) mice with L. mexicana. We show that
      FcgammaRIII KO mice are resistant to L. mexicana infection, resolving lesions in
      association with a stronger gamma interferon response, similar to IL-10 KO mice,
      with parasite control by 12 weeks. We found that the Leishmania-specific IgG
      response is unaltered in FcgammaRIII KO mice compared with that in wild-type
      controls. The frequencies of IL-10 production from lymph node CD25(+) CD4(+) T
      cells are the same in KO and wild-type mice, and depletion of CD25(+) cells did
      not alter the course of infection, implying that T(reg) cells may not be the
      mechanism for susceptibility to L. mexicana infection, unlike for L. major
      infection. However, IL-10 mRNA was greatly diminished in the lesions of
      FcgammaRIII KO mice compared to that of B6 controls. Furthermore, macrophages
      from FcgammaRIII KO and FcRgamma KO mice have the same profound defect in IL-10
      production induced by IgG-opsonized amastigotes. We also found IL-10-dependent
      (major) and -independent (minor) inhibition of IL-12 mediated by FcgammaRIII, as
      well as parasite-mediated inhibition of IL-12 and induction of IL-10, independent
      of FcgammaR. Our data demonstrate a specific role for FcgammaRIII in suppressing
      protective immunity in L. mexicana infection, likely through macrophage IL-10
      production in the lesion.

PMID- 18070891
TI  - Chlamydia pneumoniae infection increases adherence of mouse macrophages to mouse
      endothelial cells in vitro and to aortas ex vivo.
AB  - Interactions between monocytes/macrophages and endothelial cells play an
      important role in the pathogenesis of atherosclerosis, and the adherence of
      monocytes to the arterial endothelium is one of the early events in
      atherogenesis. In the present study, peritoneal macrophages harvested from green
      fluorescent protein (GFP) transgenic mice were used to analyze how Chlamydia
      pneumoniae infection affects the adherence of GFP-macrophages to mouse
      endothelial cells in vitro and to the aorta from normolipidemic and
      hyperlipidemic mice ex vivo. In vitro studies showed that C. pneumoniae-infected
      GFP-macrophages adhered better than uninfected macrophages to endothelial cells
      and GFP-macrophages adhered better to infected than uninfected endothelial cells.
      The ex vivo studies showed that C. pneumoniae-infected macrophages adhered better
      than uninfected macrophages to aortas from both normolipidemic and hyperlipidemic
      C57BL/6J mice and apolipoprotein E (ApoE)-deficient mice. In contrast, adherence
      of C. pneumoniae-infected macrophages to the aortas of intercellular adhesion
      molecule 1 (ICAM-1) knockout mice was not enhanced, suggesting that ICAM-1 is
      crucial for activation of the adherence of C. pneumoniae-infected macrophages to
      the endothelium. In conclusion, the present study defined a homing mechanism by
      which C. pneumoniae promotes the adherence of mononuclear phagocytes to the
      endothelium at the site of atherosclerotic lesion formation to promote the
      progression of atherosclerosis.

PMID- 18070892
TI  - Characterization of the fine specificity of bovine CD8 T-cell responses to
      defined antigens from the protozoan parasite Theileria parva.
AB  - Immunity against the bovine intracellular protozoan parasite Theileria parva has
      been shown to be mediated by CD8 T cells. Six antigens targeted by CD8 T cells
      from T. parva-immune cattle of different major histocompatibility complex (MHC)
      genotypes have been identified, raising the prospect of developing a subunit
      vaccine. To facilitate further dissection of the specificity of protective CD8 T
      cell responses and to assist in the assessment of responses to vaccination, we
      set out to identify the epitopes recognized in these T. parva antigens and their
      MHC restriction elements. Nine epitopes in six T. parva antigens, together with
      their respective MHC restriction elements, were successfully identified. Five of
      the cytotoxic-T-lymphocyte epitopes were found to be restricted by products of
      previously described alleles, and four were restricted by four novel restriction
      elements. Analyses of CD8 T-cell responses to five of the epitopes in groups of
      cattle carrying the defined restriction elements and immunized with live
      parasites demonstrated that, with one exception, the epitopes were consistently
      recognized by animals of the respective genotypes. The analysis of responses was
      extended to animals immunized with multiple antigens delivered in separate
      vaccine constructs. Specific CD8 T-cell responses were detected in 19 of 24
      immunized cattle. All responder cattle mounted responses specific for antigens
      for which they carried an identified restriction element. By contrast, only 8 of
      19 responder cattle displayed a response to antigens for which they did not carry
      an identified restriction element. These data demonstrate that the identified
      antigens are inherently dominant in animals with the corresponding MHC genotypes.

PMID- 18070893
TI  - A SacB mutagenesis strategy reveals that the Bartonella quintana variably
      expressed outer membrane proteins are required for bloodstream infection of the
      host.
AB  - Bartonella bacteria adhere to erythrocytes and persistently infect the mammalian
      bloodstream. We previously identified four highly conserved Bartonella quintana
      adhesin genes that undergo phase variation during prolonged bloodstream
      infection. The variably expressed outer membrane proteins (Vomp) encoded by these
      genes are members of the trimeric autotransporter adhesin family. Each B.
      quintana Vomp appears to contribute a different adhesion phenotype, likely
      mediated by the major variable region at the adhesive tip of each Vomp. Although
      studies document that the Vomp adhesins confer virulence phenotypes in vitro,
      little is known about in vivo virulence strategies of Bartonella. We sought to
      determine whether the B. quintana Vomp adhesins are necessary for infection in
      vivo by using a vomp null mutant. It first was necessary to develop a system to
      generate in-frame deletions of defined genes by allelic exchange in a wild-type
      Bartonella background, which had not been achieved previously. We utilized sacB
      negative selection to generate a targeted, in-frame, markerless deletion of the
      entire vomp locus in B. quintana. We also recently developed the first animal
      model for B. quintana infection, and using this model, we demonstrate here that
      the deletion of the entire vomp locus, but not the deletion of two vomp genes,
      results in a null mutant strain that is incapable of establishing bloodstream
      infection in vivo. The Vomp adhesins therefore represent critical virulence
      factors in vivo, warranting further study. Finally, our allelic exchange strategy
      provides an important advance in the genetic manipulation of all Bartonella
      species and, combined with the animal model that recapitulates human disease,
      will facilitate pathogenesis studies of B. quintana.

PMID- 18070894
TI  - Activation of IkappaB kinase and NF-kappaB is essential for Helicobacter pylori
      induced chronic gastritis in Mongolian gerbils.
AB  - The Mongolian gerbil model of Helicobacter pylori infection resembles human
      gastritis. In this study, we investigated the role of NF-kappaB activation in H.
      pylori-infected gerbils. Activated macrophages were significantly increased in H.
      pylori-infected gastric mucosa and were identified as being important cells with
      potent activation of NF-kappaB, which plays an important part in producing
      proinflammatory cytokines. Macrophage depletion by the administration of
      clodronate resulted in milder inflammation in gerbils infected with H. pylori. In
      macrophages, the inhibition of IkappaB kinase beta (IKKbeta), which is a critical
      kinase for NF-kappaB activation, resulted in lower proinflammatory cytokine
      expression caused by heat-killed H. pylori cells. Furthermore, treatment with
      IKKbeta inhibitor resulted in milder inflammation in gerbils with H. pylori
      gastritis. Collectively, our data suggest that H. pylori-mediated gastric
      inflammation critically depends on the efficient recruitment and activation of
      macrophages, with sufficient NF-kappaB activation.

PMID- 18070895
TI  - Possible role for Toll-like receptors in interaction of Fasciola hepatica
      excretory/secretory products with bovine macrophages.
AB  - Alternative activation of macrophages (Mphi) during helminth infection is a
      characteristic feature of the host immune response. Alternatively activated
      macrophages (AAMphi) are distinguished from others by high arginase 1 (Arg-1)
      activity, low nitric oxide (NO), and high interleukin 10 (IL-10) production. In
      murine models, these cells have been shown to possess anti-inflammatory
      properties. They have also been implicated in exacerbating a subsequent infection
      with a secondary pathogen. In this study we used cattle experimentally infected
      with Fasciola hepatica to monitor the kinetics of IL-4 and IL-10 over the course
      of infection. Using naive Mphi in vitro, we examined the effects of exposure to
      F. hepatica excretory/secretory products (FhepES) alone or in combination with IL
      4. Our results suggest that FhepES may work in combination with IL-4 to produce
      AAMphi. The effects of FhepES on the subsequent responses to lipopolysaccharide
      (LPS) and purified protein derivative from Mycobacterium bovis (PPD-B), which are
      bovine Toll-like receptor 4 (TLR4) and TLR2 antagonists, respectively, were also
      examined. We found that Mphi stimulated with FhepES together with LPS or PPD-B
      have reduced NO or gamma interferon production, respectively. The ability of
      FhepES to produce AAMphi was found to be heat labile and partially dependent on
      glycan residues. A possible role for TLR recognition is discussed.

PMID- 18070896
TI  - Humoral responses to Plasmodium falciparum blood-stage antigens and association
      with incidence of clinical malaria in children living in an area of seasonal
      malaria transmission in Burkina Faso, West Africa.
AB  - There is longstanding evidence that immunoglobulin G (IgG) has a role in
      protection against clinical malaria, and human antibodies of the cytophilic
      subclasses are thought to be particularly critical in this respect. In this
      cohort study, 286 Burkinabe children 6 months to 15 years old were kept under
      malaria surveillance in order to assess the protective role of antibody responses
      against four antigens which are currently being evaluated as vaccine candidates:
      apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3,
      and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses
      were measured just before the malaria transmission season. The incidence of
      malaria was 2.4 episodes per child year of risk. After adjusting for the
      confounding effects of age, the level of total IgG to GLURP was strongly
      associated with reduced malaria incidence (incidence rate ratio associated with a
      doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94; P = 0.009.);
      there was a borderline statistically significant association between the level of
      total IgG to MSP3 and malaria incidence and no evidence of an association for
      total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only
      IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced
      risk of clinical malaria. There was no evidence of an interaction between
      responses to AMA1 and baseline parasitemia in their effects on malaria incidence.
      Currently included in malaria vaccine formulations for clinical trials in humans,
      these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria
      vaccine development.

PMID- 18070897
TI  - Global transcriptional profile of Mycobacterium tuberculosis during THP-1 human
      macrophage infection.
AB  - During lung infection, Mycobacterium tuberculosis resides in macrophages and
      subverts the bactericidal mechanisms of these professional phagocytes.
      Comprehension of this host-pathogen relationship is fundamental for the
      development of new therapies to cure and prevent tuberculosis. In this work, we
      analyzed the transcriptional profile of M. tuberculosis infecting human
      macrophage-like THP-1 cells in order to identify putative bacterial pathogenic
      factors that can be relevant for the intracellular survival of M. tuberculosis.
      We compared the gene expression profile of M. tuberculosis H37Rv after 4 h and 24
      h of infection of human macrophage-like THP-1 cells with the gene expression
      profile of the strain growing exponentially in broth cultures. We found 585 genes
      expressed differentially by intracellular M. tuberculosis. An analysis of the
      gene expression profile of M. tuberculosis inside THP-1 cells suggests the
      perturbation of the cell envelope as a major intracellular stress inside THP-1
      macrophages.

PMID- 18070898
TI  - Transcriptome changes in Mycoplasma hyopneumoniae during infection.
AB  - Mycoplasma hyopneumoniae causes swine pneumonia and contributes significantly to
      the porcine respiratory disease complex. The mechanisms of pathogenesis are
      difficult to address, since there is a lack of genetic tools, but microarrays are
      available and can be used to study transcriptional changes that occur during
      disease as a way to identify important virulence-related genes. Mycoplasmas were
      collected from bronchial alveolar lavage samples and compared to broth-grown
      cells using microarrays. Bronchial alveolar lavage was performed on pigs 28 days
      postinfection, and mycoplasmas were isolated by differential centrifugation.
      Mycoplasma RNA-enriched preparations were then obtained from total RNA by
      subtracting eucaryotic ribosomal and messenger RNAs. Labeled cDNAs were generated
      with mycoplasma open reading frame-specific primers. Nine biological replicates
      were analyzed. During lung infection, our analysis indicated that 79 M.
      hyopneumoniae genes were differentially expressed (P < 0.01), at a false
      discovery rate of <2.7%. Of the down-regulated genes, 28 of 46 (61%) lacked an
      assigned function, in comparison to 21 of 33 (63%) of up-regulated genes. Four
      down-regulated genes and two up-regulated genes encoded putative lipoproteins.
      secA (mhp295) (P = 0.003) and two glycerol transport permease genes (potA
      [mhp380; P = 0.006] and ugpA [mhp381; P = 0.003]) were up-regulated in vivo.
      Elongation factor EF-G (fusA [mhp083]) (P = 0.002), RNA polymerase beta chain
      (rpoC [mhp635]) (P = 0.003), adenylate kinase (adk [mhp208]) (P = 0.001), prolyl
      aminoacyl tRNA synthetase (proS [mhp397]) (P = 0.009), and cysteinyl-tRNA
      synthetase (cysS [mhp661]) (P < 0.001) were down-regulated in vivo.

PMID- 18070899
TI  - NF-kappaB activation during acute Helicobacter pylori infection in mice.
AB  - Nuclear factor kappaB (NF-kappaB) plays a key regulatory role in host cell
      responses to Helicobacter pylori infection in humans. Although mice are routinely
      used as a model to study H. pylori pathogenesis, the role of NF-kappaB in murine
      cell responses to helicobacters has not been studied in detail. We thus
      investigated the abilities of different Helicobacter isolates to induce NF-kappaB
      dependent responses in murine gastric epithelial cells (GECs) and in transgenic
      mice harboring an NF-kappaB-responsive lacZ reporter gene. H. pylori and
      Helicobacter felis strains up-regulated the synthesis in mouse GECs of the NF
      kappaB-dependent chemokines KC (CXCL1) and MIP-2 (CXCL2). These responses were
      cag pathogenicity island (cagPAI) independent and could be abolished by
      pretreatment with a pharmacological inhibitor of NF-kappaB. Consistent with the
      in vitro data, experimental Helicobacter infection of transgenic mice resulted in
      increased numbers of GECs with nuclear beta-galactosidase activity, which is
      indicative of specific NF-kappaB activation. The numbers of beta-galactosidase
      positive cells in mice were significantly increased at day 1 postinoculation with
      wild-type H. pylori strains harboring or not harboring a functional cagPAI,
      compared to naive animals (P = 0.007 and P = 0.04, respectively). Strikingly,
      however, no differences were observed in the levels of gastric NF-kappaB
      activation at day 1 postinoculation with H. felis or at day 30 or 135
      postinoculation with H. pylori. This work demonstrates for the first time the
      induction of NF-kappaB activation within gastric mucosal cells during acute H.
      pylori infection. Furthermore, the data suggest that helicobacters may be able to
      regulate NF-kappaB signaling during chronic infection.

PMID- 18070900
TI  - Genetic diversity among Escherichia coli O157:H7 isolates and identification of
      genes linked to human infections.
AB  - An Escherichia coli oligonucleotide microarray based on three sequenced genomes
      was validated for comparative genomic microarray hybridization and used to study
      the diversity of E. coli O157 isolates from human infections and food and animal
      sources. Among 26 test strains, 24 (including both Shiga toxin [Stx]-positive and
      -negative strains) were found to be related to the two sequenced E. coli O157:H7
      strains, EDL933 and Sakai. However, these strains showed much greater genetic
      diversity than those reported previously, and most of them could not be
      categorized as either lineage I or II. Some genes were found more often in
      isolates from human than from nonhuman sources; e.g., ECs1202 and ECs2976,
      associated with stx2AB and stx1AB, were in all isolates from human sources but in
      only 40% of those from nonhuman sources. Some (but not all) lineage I-specific or
      -dominant genes were also more frequently associated with isolates from human.
      The results suggested that it might be more effective to concentrate our efforts
      on finding markers that are directly related to infection rather than those
      specific to certain lineages. In addition, two Stx-negative O157 cattle isolates
      (one confirmed to be H7) were significantly different from other Stx-positive and
      -negative E. coli O157:H7 strains and were more similar to MG1655 in their gene
      content. This work demonstrates that not all E. coli O157:H7 strains belong to
      the same clonal group, and those that were similar to E. coli K-12 might be less
      virulent.

PMID- 18070901
TI  - Interferons increase cell resistance to Staphylococcal alpha-toxin.
AB  - Many bacterial pathogens, including Staphylococcus aureus, use a variety of pore
      forming toxins as important virulence factors. Staphylococcal alpha-toxin, a
      prototype beta-barrel pore-forming toxin, triggers the release of proinflammatory
      mediators and induces primarily necrotic death in susceptible cells. However,
      whether host factors released in response to staphylococcal infections may
      increase cell resistance to alpha-toxin is not known. Here we show that prior
      exposure to interferons (IFNs) prevents alpha-toxin-induced membrane
      permeabilization, the depletion of ATP, and cell death. Moreover, pretreatment
      with IFN-alpha decreases alpha-toxin-induced secretion of interleukin 1beta (IL
      1beta). IFN-alpha, IFN-beta, and IFN-gamma specifically protect cells from alpha
      toxin, whereas tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-4 have no
      effects. Furthermore, we show that IFN-alpha-induced protection from alpha-toxin
      is not dependent on caspase-1 or mitogen-activated protein kinases, but requires
      protein synthesis and fatty acid synthase activity. Our results demonstrate that
      IFNs may increase cell resistance to staphylococcal alpha-toxin via the
      regulation of lipid metabolism and suggest that interferons play a protective
      role during staphylococcal infections.

PMID- 18070902
TI  - Immunogenic and plasminogen-binding surface-associated alpha-enolase of
      Trichomonas vaginalis.
AB  - Trichomonas vaginalis is a protist that causes the most common human sexually
      transmitted infection. A T. vaginalis cDNA expression library was screened with
      pooled sera from patients with trichomoniasis. A highly reactive cDNA clone of
      1,428 bp encoded a trichomonad protein of 472 amino acids with sequence identity
      to alpha-enolase (tv-eno1). The sequence alignment confirmed the highly conserved
      nature of the enzyme with 65% to 84% identity among organisms. The expression of
      tv-eno1 was up-regulated by contact of parasites with vaginal epithelial cells,
      and this is the first report demonstrating up-regulation by cytoadherence of a
      plasminogen-binding alpha-enolase in T. vaginalis. Immunofluorescence with
      monoclonal antibody of nonpermeabilized trichomonads showed tv-ENO1 on the
      surface. The recombinant tv-ENO1 was expressed in Escherichia coli as a
      glutathione S-transferase (GST)::tv-ENO1 fusion protein, which was cleaved using
      thrombin to obtain affinity-purified recombinant tv-ENO1 protein (tv-rENO1)
      detectable in immunoblots by sera of patients. Immobilized tv-rENO1 bound human
      plasminogen in a dose-dependent manner, and plasminogen binding by tv-rENO1 was
      confirmed in a ligand blot assay. The plasminogen-specific inhibitor epsilon
      aminocaproic acid blocked the tv-rENO1-plasminogen association, indicating that
      lysines play a role in binding to tv-rENO1. Further, both parasites and tv-rENO1
      activate plasminogen to plasmin that is mediated by tissue plasminogen activator.
      These data indicate that as with other bacterial pathogens, tv-ENO1 is an
      anchorless, surface-associated glycolytic enzyme of T. vaginalis.

PMID- 18070903
TI  - Subunit vaccine against the seven serotypes of botulism.
AB  - Botulinum neurotoxins (BoNTs) are the most toxic proteins for humans and are
      classified as category A toxins. There are seven serotypes of BoNTs defined by
      the lack of cross-serotype toxin neutralization. Thus, an effective vaccine must
      neutralize each BoNT serotype. BoNTs are organized as dichain A-B toxins, where
      the N-terminal domain (light chain) is a zinc metalloprotease targeting soluble
      NSF attachment receptor proteins that is linked to the C-terminal domain (heavy
      chain [HC]) by a disulfide bond. The HC comprises a translocation domain and a C
      terminal receptor binding domain (HCR). HCRs of the seven serotypes of BoNTs
      (hepta-HCR) were engineered for expression in Escherichia coli, and each HCR was
      purified from E. coli lysates. Immunization of mice with the E. coli-derived
      hepta-serotype HCR vaccine elicited an antibody response to each of the seven
      BoNT HCRs and neutralized challenge by 10,000 50% lethal doses of each of the
      seven BoNT serotypes. A solid-phase assay showed that the anti-hepta-serotype HCR
      sera inhibited the binding of HCR serotypes A and B to the ganglioside GT1b, the
      first step in BoNT intoxication of neurons. This is the first E. coli-derived
      vaccine that effectively neutralizes each of the seven BoNT serotypes.

PMID- 18070904
TI  - Evasion of innate immune responses: evidence for mannose binding lectin
      inhibition of tumor necrosis factor alpha production by macrophages in response
      to Blastomyces dermatitidis.
AB  - Serum factors, including mannose binding lectins (MBL), influence innate
      responses to microbes. Little is known about the effects of serum factors or MBL
      on the interaction of Blastomyces dermatitidis, a pulmonary fungal pathogen, with
      macrophages or on tumor necrosis factor alpha (TNF-alpha) production. Since
      macrophage production of TNF-alpha is an important innate immune response, we
      examined a mouse peritoneal macrophage (PM) cell line (RAW) and resident PM from
      CD-1 mice to study TNF-alpha production by PM stimulated with heat-killed (HK) or
      live B. dermatitidis yeast cells. Mouse serum and heat-inactivated mouse serum
      inhibited TNF-alpha production 94% when macrophages were stimulated by B.
      dermatitidis, whereas mouse immunoglobulin G (IgG) did not have this effect. HK
      B. dermatitidis incubated with serum and then washed also failed to stimulate
      significant TNF-alpha production by PM. By the sandwich immunofluorescent
      antibody (IFA) method with anti-mouse MBL (MBL-A or -C), we showed that serum MBL
      bound to B. dermatitidis. When serum was absorbed with HK B. dermatitidis or live
      B. dermatitidis, absorbed serum failed to significantly inhibit TNF-alpha
      production by RAW cells plus B. dermatitidis, and immunoblotting showed that
      absorbed serum was depleted of MBL-C. If serum was absorbed with live B.
      dermatitidis, unbound serum was eluted, and bound serum factor(s) (BS) was
      released with guanidine buffer, BS inhibited TNF-alpha production by PM plus B.
      dermatitidis in a concentration-dependent manner. BS contained MBL-C, which bound
      B. dermatitidis, as shown by IFA assay. 1,3-beta-Glucan stimulated TNF-alpha
      production by PM, and this was inhibited by mouse serum. Treatment of B.
      dermatitidis with anti-1,3-beta-glucan antibody inhibited TNF-alpha production by
      PM. With anti-1,3-beta-glucan antibody, we showed by IFA assay that B.
      dermatitidis contained 1,3-beta-glucan. In an IFA study with B. dermatitidis,
      serum with an anti-mouse IgG conjugate did not result in fluorescence, yet serum
      blocked IFA staining of B. dermatitidis by anti-1,3-beta-glucan IgG antibody.
      This indicated that non-IgG serum factors binding to B. dermatitidis prevented
      access to 1,3-beta-glucan by anti-1,3-beta-glucan antibody. These results suggest
      that the mechanism of inhibition of the innate proinflammatory immune response of
      PM to B. dermatitidis is mediated by serum MBL binding to B. dermatitidis at 1,3
      beta-glucan sites or sterically masking 1,3-beta-glucan sites, thus preventing
      1,3-beta-glucan stimulation of PM for TNF-alpha production.

PMID- 18070905
TI  - Sequence diversity of the Trypanosoma cruzi complement regulatory protein family.
AB  - As a central component of innate immunity, complement activation is a critical
      mechanism of containment and clearance of microbial pathogens in advance of the
      development of acquired immunity. Several pathogens restrict complement
      activation through the acquisition of host proteins that regulate complement
      activation or through the production of their own complement regulatory molecules
      (M. K. Liszewski, M. K. Leung, R. Hauhart, R. M. Buller, P. Bertram, X. Wang, A.
      M. Rosengard, G. J. Kotwal, and J. P. Atkinson, J. Immunol. 176:3725-3734, 2006;
      J. Lubinski, L. Wang, D. Mastellos, A. Sahu, J. D. Lambris, and H. M. Friedman,
      J. Exp. Med. 190:1637-1646, 1999). The infectious stage of the protozoan parasite
      Trypanosoma cruzi produces a surface-anchored complement regulatory protein (CRP)
      that functions to inhibit alternative and classical pathway complement activation
      (K. A. Norris, B. Bradt, N. R. Cooper, and M. So, J. Immunol. 147:2240-2247,
      1991). This study addresses the genomic complexity of the T. cruzi CRP and its
      relationship to the T. cruzi supergene family comprising active trans-sialidase
      (TS) and TS-like proteins. The TS superfamily consists of several functionally
      distinct subfamilies that share a characteristic sialidase domain at their amino
      termini. These TS families include active TS, adhesions, CRPs, and proteins of
      unknown functions (G. A. Cross and G. B. Takle, Annu. Rev. Microbiol. 47:385-411,
      1993). A sequence comparison search of GenBank using BLASTP revealed several full
      length paralogs of CRP. These proteins share significant homology at their amino
      termini and a strong spatial conservation of cysteine residues. Alternative
      pathway complement regulation was confirmed for CRP paralogs with 58% (low) and
      83% (high) identity to AAB49414. CRPs are functionally similar to the microbial
      and mammalian proteins that regulate complement activation. Sequence alignment of
      mammalian complement control proteins to CRP showed that these sequences are
      distinct, supporting a convergent evolutionary pathway. Finally, we show that a
      clonal line of T. cruzi expresses multiple unique copies of CRP that are
      differentially recognized by patient sera.

PMID- 18070906
TI  - Enterobacter sakazakii invasion in human intestinal Caco-2 cells requires the
      host cell cytoskeleton and is enhanced by disruption of tight junction.
AB  - Enterobacter sakazakii is an opportunistic pathogen that causes systemic
      bacteremia and meningitis with high mortality, and powdered infant formula is a
      frequent source of this bacterium. However, the mechanisms that this organism
      uses to invade and translocate through the intestinal barrier are unknown. Using
      Caco-2 epithelial cells, we were able to demonstrate penetration of E. sakazakii
      and to determine invasion-associated properties. We found that E. sakazakii entry
      and invasion were dependent on the exposure time and multiplicity of infection
      and required bacterial de novo protein synthesis but was independent of cell
      polarity in the presence of tight junctions. Moreover, the presence of actin
      filaments and microtubule structures was required, and disruption of the tight
      junction significantly enhanced the initial association with Caco-2 cells and the
      efficiency of invasion, which provides a possible explanation for the
      preferential occurrence of this infection in babies and neonates. This is the
      first description of E. sakazakii invasion of host intestinal cells, and our
      findings suggest that this emerging pathogen employs a novel invasion mechanism
      for development of systemic infection.

PMID- 18070907
TI  - Effective production and purification of the glycosylated TSOL18 antigen, which
      is protective against pig cysticercosis.
AB  - Cysticercosis caused by Taenia solium metacestodes is a worldwide public health
      problem. Important progress in the development of effective and practical
      vaccines against this disease has been made. In this study, the promising T.
      solium oncospheral vaccine candidate named TSOL18 antigen was produced in a 5
      liter fermentor. During the process of fermentation, the pH of the culture was
      always kept below 5.0, and in order to prevent foaming, an antifoam agent was
      added. In addition, the oxygen content of the culture was constantly kept at >50%
      in our experiment. A high level of the glycosylated protein (2.5 g/liter) was
      obtained, and the protein was easily purified by gel chromatography. Vaccination
      trials showed that the recombinant TSOL18 antigen induced 94 and 100% reductions
      in metacestode burdens in vaccinated pigs, obviously higher than the 89%
      reduction in pigs immunized with cysticercus crude extracts in trial 1. These are
      very promising results in the development of an efficient tool to control
      cysticercosis in Asia.

PMID- 18070908
TI  - Dose-response model for Listeria monocytogenes-induced stillbirths in nonhuman
      primates.
AB  - A dose-response model using rhesus monkeys as a surrogate for pregnant women
      indicates that oral exposure to 10(7) CFU of Listeria monocytogenes results in
      about 50% stillbirths. Ten of 33 pregnant rhesus monkeys exposed orally to a
      single dose of 10(2) to 10(10) CFU of L. monocytogenes had stillbirths. A log
      logistic model predicts a dose affecting 50% of animals at 10(7) CFU, comparable
      to an estimated 10(6) CFU based on an outbreak among pregnant women but much less
      than the extrapolated estimate (10(13) CFU) from the FDA-U.S. Department of
      Agriculture-CDC risk assessment using an exponential curve based on mouse data.
      Exposure and etiology of the disease are the same in humans and primates but not
      in mice. This information will aid in risk assessment, assist policy makers, and
      provide a model for mechanistic studies of L. monocytogenes-induced stillbirths.

PMID- 18070909
TI  - Toll-like receptors and leishmaniasis.

PMID- 18070910
TI  - RMD-1, a novel microtubule-associated protein, functions in chromosome
      segregation in Caenorhabditis elegans.
AB  - For proper chromosome segregation, the sister kinetochores must attach to
      microtubules extending from the opposite spindle poles. Any errors in microtubule
      attachment can induce aneuploidy. In this study, we identify a novel conserved
      Caenorhabditis elegans microtubule-associated protein, regulator of microtubule
      dynamics 1 (RMD-1), that localizes to spindle microtubules and spindle poles.
      Depletion of RMD-1 induces severe defects in chromosome segregation, probably
      through merotelic attachments between microtubules and chromosomes. Although rmd
      1 embryos also have a mild defect in microtubule growth, we find that mutants of
      the microtubule growth regulator XMAP215/ZYG-9 show much weaker segregation
      defects. This suggests that the microtubule growth defect in rmd-1 embryos does
      not cause abnormal chromosome segregation. We also see that RMD-1 interacts with
      aurora B in vitro. Our results suggest that RMD-1 functions in chromosome
      segregation in C. elegans embryos, possibly through the aurora B-mediated
      pathway. Human homologues of RMD-1 could also bind microtubules, which would
      suggest a function for these proteins in chromosome segregation during mitosis in
      other organisms as well.

PMID- 18070911
TI  - In vivo induction of postsynaptic molecular assembly by the cell adhesion
      molecule Fasciclin2.
AB  - Cell adhesion molecules (CAMs) are thought to mediate interactions between
      innervating axons and their targets. However, such interactions have not been
      directly observed in vivo. In this paper, we study the function and dynamics of
      Fasciclin2 (Fas2), a homophilic CAM expressed both pre- and postsynaptically
      during neuromuscular synapse formation in Drosophila melanogaster. We apply live
      imaging of functional fluorescent fusion proteins expressed in muscles and find
      that Fas2 and Discs-Large (Dlg; a scaffolding protein known to bind Fas2)
      accumulate at the synaptic contact site soon after the arrival of the nerve.
      Genetic, deletion, and photobleaching analyses suggest that Fas2-mediated trans
      synaptic adhesion is important for the postsynaptic accumulation of both Fas2
      itself and Dlg. In fas2 mutants, many aspects of synapse formation appear normal;
      however, we see a reduction in the synaptic accumulation of Scribble (another
      scaffolding protein) and glutamate receptor subunits GluRIIA and GluRIIB. We
      propose that Fas2 mediates trans-synaptic adhesion, which contributes to
      postsynaptic molecular assembly at the onset of synaptogenesis.

PMID- 18070912
TI  - Regulation of lamellipodial persistence, adhesion turnover, and motility in
      macrophages by focal adhesion kinase.
AB  - Macrophages are a key component of the innate immune system. In this study, we
      investigate how focal adhesion kinase (FAK) and the related kinase Pyk2 integrate
      adhesion signaling and growth factor receptor signaling to regulate diverse
      macrophage functions. Primary bone marrow macrophages isolated from mice in which
      FAK is conditionally deleted from cells of the myeloid lineage exhibited elevated
      protrusive activity, altered adhesion dynamics, impaired chemotaxis, elevated
      basal Rac1 activity, and a marked inability to form stable lamellipodia necessary
      for directional locomotion. The contribution of FAK to macrophage function in
      vitro was substantiated in vivo by the finding that recruitment of monocytes to
      sites of inflammation was impaired in the absence of FAK. Decreased Pyk2
      expression in primary macrophages also resulted in a diminution of invasive
      capacity. However, the combined loss of FAK and Pyk2 had no greater effect than
      the loss of either molecule alone, indicating that both kinases function within
      the same pathway to promote invasion.

PMID- 18070913
TI  - Sorting switch of mitochondrial presequence translocase involves coupling of
      motor module to respiratory chain.
AB  - The mitochondrial presequence translocase transports preproteins to either matrix
      or inner membrane. Two different translocase forms have been identified: the
      matrix transport form, which binds the heat-shock protein 70 (Hsp70) motor, and
      the inner membrane-sorting form, which lacks the motor but contains translocase
      of inner mitochondrial membrane 21 (Tim21). The sorting form interacts with the
      respiratory chain in a Tim21-dependent manner. It is unknown whether the
      respiratory chain-bound translocase transports preproteins and how the switch
      between sorting form and motor form occurs. We report that the respiratory chain
      bound translocase contains preproteins in transit and, surprisingly, not only
      sorted but also matrix-targeted preproteins. Presequence translocase-associated
      motor (Pam) 16 and 18, two regulatory components of the six-subunit motor,
      interact with the respiratory chain independently of Tim21. Thus, the respiratory
      chain-bound presequence translocase is not only active in preprotein sorting to
      the inner membrane but also in an early stage of matrix translocation. The motor
      does not assemble en bloc with the translocase but apparently in a step-wise
      manner with the Pam16/18 module before the Hsp70 core.

PMID- 18070914
TI  - Par3 functions in the biogenesis of the primary cilium in polarized epithelial
      cells.
AB  - Par3 is a PDZ protein important for the formation of junctional complexes in
      epithelial cells. We have identified an additional role for Par3 in membrane
      biogenesis. Although Par3 was not required for maintaining polarized apical or
      basolateral membrane domains, at the apical surface, Par3 was absolutely
      essential for the growth and elongation of the primary cilium. The activity
      reflected its ability to interact with kinesin-2, the microtubule motor
      responsible for anterograde transport of intraflagellar transport particles to
      the tip of the growing cilium. The Par3 binding partners Par6 and atypical
      protein kinase C interacted with the ciliary membrane component Crumbs3 and we
      show that the PDZ binding motif of Crumbs3 was necessary for its targeting to the
      ciliary membrane. Thus, the Par complex likely serves as an adaptor that couples
      the vectorial movement of at least a subset of membrane proteins to microtubule
      dependent transport during ciliogenesis.

PMID- 18070915
TI  - Actin-dependent intranuclear repositioning of an active gene locus in vivo.
AB  - Although bulk chromatin is thought to have limited mobility within the interphase
      eukaryotic nucleus, directed long-distance chromosome movements are not unknown.
      Cajal bodies (CBs) are nuclear suborganelles that nonrandomly associate with
      small nuclear RNA (snRNA) and histone gene loci in human cells during interphase.
      However, the mechanism responsible for this association is uncertain. In this
      study, we present an experimental system to probe the dynamic interplay of CBs
      with a U2 snRNA target gene locus during transcriptional activation in living
      cells. Simultaneous four-dimensional tracking of CBs and U2 genes reveals that
      target loci are recruited toward relatively stably positioned CBs by long-range
      chromosomal motion. In the presence of a dominant-negative mutant of beta-actin,
      the repositioning of activated U2 genes is markedly inhibited. This supports a
      model in which nuclear actin is required for these rapid, long-range chromosomal
      movements.

PMID- 18070916
TI  - How genes find their way inside the cell nucleus.
AB  - Recent progress in live cell imaging suggests a role for nuclear actin in
      chromatin movement. In this issue, for the first time, a gene locus moving toward
      a subnuclear compartment was tracked. Motion of the locus is actin dependent,
      raising the question of whether chromatin movements are random or directed.

PMID- 18070917
TI  - The mouse polyubiquitin gene Ubb is essential for meiotic progression.
AB  - Ubiquitin is encoded in mice by two polyubiquitin genes, Ubb and Ubc, that are
      considered to be stress inducible and two constitutively expressed monoubiquitin
      (Uba) genes. Here we report that targeted disruption of Ubb results in male and
      female infertility due to failure of germ cells to progress through meiosis I and
      hypogonadism. In the absence of Ubb, spermatocytes and oocytes arrest during
      meiotic prophase, before metaphase of the first meiotic division. Although
      cellular ubiquitin levels are believed to be maintained by a combination of
      functional redundancy among the four ubiquitin genes, stress inducibility of the
      two polyubiquitin genes, and ubiquitin recycling by proteasome-associated
      isopeptidases, our results indicate that ubiquitin is required for and consumed
      during meiotic progression. The striking similarity of the meiotic phenotype in
      Ubb(-/-) germ cells to the sporulation defect in fission yeast
      (Schizosaccharomyces pombe) lacking a polyubiquitin gene suggests that a meiotic
      role of the polyubiquitin gene has been conserved throughout eukaryotic
      evolution.

PMID- 18070918
TI  - Genome-wide analysis identifies MYND-domain protein Mub1 as an essential factor
      for Rpn4 ubiquitylation.
AB  - The proteasome homeostasis in Saccharomyces cerevisiae is regulated by a negative
      feedback circuit in which the Rpn4 transcription factor upregulates the
      proteasome genes and is rapidly degraded by the proteasome. Previous work has
      identified Ubr2 and Rad6 as the cognate E3 and E2 enzymes for Rpn4
      ubiquitylation. However, our recent attempts to ubiquitylate Rpn4 using purified
      Ubr2 and Rad6 proteins in a reconstitution system have been unsuccessful,
      suggesting that an additional factor is required for Rpn4 ubiquitylation. Here,
      we screened the entire collection of the single-gene-deletion yeast mutants
      generated by the Saccharomyces Genome Deletion Project and identified the
      mub1Delta mutant defective in ubiquitin-dependent degradation of Rpn4. An in
      vitro reconstitution ubiquitylation assay confirms that Mub1 is the missing
      factor for Rpn4 ubiquitylation. We further show that Mub1 directly interacts with
      Ubr2 and Rpn4. The MYND domain of Mub1 may play an important role in Rpn4
      ubiquitylation. Interestingly, Mub1 itself is a short-lived protein and its
      degradation is dependent on the Ubr2/Rad6 ubiquitin ligase. Together, these data
      suggest that Mub1 and Ubr2 cooperate to transfer ubiquitin to Rpn4 from Rad6 and
      that Mub1 may switch from a partner to a substrate of the Ubr2/Rad6 ubiquitin
      ligase.

PMID- 18070919
TI  - Di- and tri- but not monomethylation on histone H3 lysine 36 marks active
      transcription of genes involved in flowering time regulation and other processes
      in Arabidopsis thaliana.
AB  - Histone lysines can be mono-, di-, or trimethylated, providing an ample magnitude
      of epigenetic information for transcription regulation. In fungi, SET2 is the
      sole methyltransferase responsible for mono-, di-, and trimethylation of H3K36.
      Here we show that in Arabidopsis thaliana, the degree of H3K36 methylation is
      regulated by distinct methyltransferases. The SET2 homologs SDG8 and SDG26 each
      can methylate oligonucleosomes in vitro, and both proteins are localized in the
      nucleus. While the previously reported loss-of-function sdg8 mutants have an
      early-flowering phenotype, the loss-of-function sdg26 mutants show a late
      flowering phenotype. Consistently, several MADS-box flowering repressors are down
      regulated by sdg8 but up-regulated by sdg26. The sdg8 but not the sdg26 mutant
      plants show a dramatically reduced level of both di- and trimethyl-H3K36 and an
      increased level of monomethyl-H3K36. SDG8 is thus specifically required for di-
      and trimethylation of H3K36. Our results further establish that H3K36 di- and tri
      but not monomethylation correlates with transcription activation. Finally, we
      show that SDG8 and VIP4, which encodes a component of the PAF1 complex, act
      independently and synergistically in transcription regulation. Together our
      results reveal that the deposition of H3K36 methylation is finely regulated,
      possibly to cope with the complex regulation of growth and development in higher
      eukaryotes.

PMID- 18070920
TI  - The human T-cell leukemia virus type 1 tax protein confers CBP/p300 recruitment
      and transcriptional activation properties to phosphorylated CREB.
AB  - The human T-cell leukemia virus-encoded oncoprotein Tax is a potent activator of
      viral transcription. Tax function is strictly dependent upon the cellular
      transcription factor CREB, and together they bind cAMP response elements within
      the viral promoter and mediate high-level viral transcription. Signal-dependent
      CREB phosphorylation at Ser(133) (pCREB) correlates with the activation of
      transcription. This activation has been attributed to recruitment of the
      coactivators CBP/p300 via physical interaction with the KIX domain. Here we show
      that the promoter-bound Tax/pCREB complex strongly recruits the recombinant,
      purified full-length coactivators CBP and p300. Additionally, the promoter-bound
      Tax/pCREB (but not Tax/CREB) complex recruits native p300 and potently activates
      transcription from chromatin templates. Unexpectedly, pCREB alone failed to
      detectably recruit the full-length coactivators, despite strong binding to KIX.
      These observations are in marked contrast to those in published studies that have
      characterized the physical interaction between KIX and pCREB and extrapolated
      these results to the full-length proteins. Consistent with our observation that
      pCREB is deficient for binding of CBP/p300, pCREB alone failed to support
      transcriptional activation. These data reveal that phosphorylation of CREB is not
      sufficient for CBP/p300 recruitment and transcriptional activation. The
      regulation of transcription by pCREB is therefore more complex than is generally
      recognized, and coregulators, such as Tax, likely play a critical role in the
      modulation of pCREB function.

PMID- 18070921
TI  - Yap5 is an iron-responsive transcriptional activator that regulates vacuolar iron
      storage in yeast.
AB  - The transporter Ccc1 imports iron into the vacuole, which is the major site of
      iron storage in fungi and plants. CCC1 mRNA is destabilized under low-iron
      conditions by the binding of Cth1 and Cth2 to the 3' untranslated region (S.
      Puig, E. Askeland, and D. J. Thiele, Cell 120:99-110, 2005). Here, we show that
      the transcription of CCC1 is stimulated by iron through a Yap consensus site in
      the CCC1 promoter. We identified YAP5 as being the iron-sensitive transcription
      factor and show that a yap5Delta strain is sensitive to high iron. Green
      fluorescent protein-tagged Yap5 is localized to the nucleus and occupies the CCC1
      promoter independent of the iron concentration. Yap5 contains two cysteine-rich
      domains, and the mutation of the cysteines to alanines in each of the domains
      affects the transcription of CCC1 but not DNA binding. The fusion of the Yap5
      cysteine-containing domains to a GAL4 DNA binding domain results in iron
      sensitive GAL1-lacZ expression. Iron affects the sulfhydryl status of Yap5, which
      is indicative of the generation of intramolecular disulfide bonds. These results
      show that Yap5 is an iron-sensing transcription factor and that iron regulates
      transcriptional activation.

PMID- 18070922
TI  - Fibulin-2 is dispensable for mouse development and elastic fiber formation.
AB  - Fibulin-2 is an extracellular matrix protein belonging to the five-member fibulin
      family, of which two members have been shown to play essential roles in elastic
      fiber formation during development. Fibulin-2 interacts with two major
      constituents of elastic fibers, tropoelastin and fibrillin-1, in vitro and
      localizes to elastic fibers in many tissues in vivo. The protein is prominently
      expressed during morphogenesis of the heart and aortic arch vessels and at early
      stages of cartilage development. To examine its role in vivo, we generated mice
      that do not express the fibulin-2 gene (Fbln2) through homologous recombination
      of embryonic stem cells. Unexpectedly, the fibulin-2-null mice were viable and
      fertile and did not display gross and anatomical abnormalities. Histological and
      ultrastructural analyses revealed that elastic fibers assembled normally in the
      absence of fibulin-2. No compensatory up-regulation of mRNAs for other fibulin
      members was detected in the aorta and skin tissue. However, in the fibulin-2 null
      aortae, fibulin-1 immunostaining was increased in the inner elastic lamina, where
      fibulin-2 preferentially localizes. The results demonstrate that fibulin-2 is not
      required for mouse development and elastic fiber formation and suggest possible
      functional redundancy between fibulin-1 and fibulin-2.

PMID- 18070923
TI  - Different requirements of the SWI/SNF complex for robust nucleosome displacement
      at promoters of heat shock factor and Msn2- and Msn4-regulated heat shock genes.
AB  - The stress response in yeast cells is regulated by at least two classes of
      transcription activators-HSF and Msn2/4, which differentially affect promoter
      chromatin remodeling. We demonstrate that the deletion of SNF2, an ATPase
      activity-containing subunit of the chromatin remodeling SWI/SNF complex,
      eliminates histone displacement, RNA polymerase II recruitment, and heat shock
      factor (HSF) binding at the HSP12 promoter while delaying these processes at the
      HSP82 and SSA4 promoters. Out of the three promoters, the double deletion of MSN2
      and MSN4 eliminates both chromatin remodeling and HSF binding only at the HSP12
      promoter, suggesting that Msn2/4 activators are primary determinants of chromatin
      disassembly at the HSP12 promoter. Unexpectedly, during heat shock the level of
      Msn2/4 at the HSP12 promoter declines. This is likely a result of promoter
      targeted Msn2/4 degradation associated with transcription complex assembly. While
      histone displacement kinetic profiles bear clear promoter specificity, the
      kinetic profiles of recovery from heat shock for all analyzed genes display an
      equal or even higher nucleosome return rate, which is to some extent delayed by
      the deletion of SNF2.

PMID- 18070924
TI  - Abnormal heart development and lung remodeling in mice lacking the hypoxia
      inducible factor-related basic helix-loop-helix PAS protein NEPAS.
AB  - Hypoxia-inducible factors (HIFs) are crucial for oxygen homeostasis during both
      embryonic development and postnatal life. Here we show that a novel HIF family
      basic helix-loop-helix (bHLH) PAS (Per-Arnt-Sim) protein, which is expressed
      predominantly during embryonic and neonatal stages and thereby designated NEPAS
      (neonatal and embryonic PAS), acts as a negative regulator of HIF-mediated gene
      expression. NEPAS mRNA is derived from the HIF-3alpha gene by alternative
      splicing, replacing the first exon of HIF-3alpha with that of inhibitory PAS.
      NEPAS can dimerize with Arnt and exhibits only low levels of transcriptional
      activity, similar to that of HIF-3alpha. NEPAS suppressed reporter gene
      expression driven by HIF-1alpha and HIF-2alpha. By generating mice with a
      targeted disruption of the NEPAS/HIF-3alpha locus, we found that homozygous
      mutant mice (NEPAS/HIF-3alpha(-)(/)(-)) were viable but displayed enlargement of
      the right ventricle and impaired lung remodeling. The expression of endothelin 1
      and platelet-derived growth factor beta was increased in the lung endothelial
      cells of NEPAS/HIF-3alpha-null mice. These results demonstrate a novel regulatory
      mechanism in which the activities of HIF-1alpha and HIF-2alpha are negatively
      regulated by NEPAS in endothelial cells, which is pertinent to lung and heart
      development during the embryonic and neonatal stages.

PMID- 18070925
TI  - Functional conservation of the glutamine-rich domains of yeast Gal11 and human
      SRC-1 in the transactivation of glucocorticoid receptor Tau 1 in Saccharomyces
      cerevisiae.
AB  - The yeast Gal11 protein, a component of the Mediator complex, is required for the
      transcriptional activation of many class II genes as a physiological target of
      various activator proteins in vivo. In this study, we identified the yeast
      (Saccharomyces cerevisiae) Mediator complex as a novel coactivator of the
      transcriptional activity of the glucocorticoid receptor (GR) tau 1 (tau1), the
      major transcriptional activation domain of the GR. GR tau1 directly interacted
      with the Mediator complex in vivo and in vitro in a Gal11 module-dependent
      manner, and the Gal11p subunit interacted directly with GR tau1. Specific amino
      acid residues within the glutamine-rich (Qr) domain of Gal11p (residues 116 to
      277) were essential for its interaction with GR tau1 and GR tau1 transactivity in
      yeast, as demonstrated by mutational analysis of the Gal11 Qr domain, which is
      highly conserved among human steroid receptor coactivator (SRC) proteins. A
      Gal11p variant, mini-Gal11p, comprised of the Mediator association and Qr domains
      of Gal11p or chimeric mini-Gal11p containing the Qr domain of SRC-1 could
      potentiate the GR tau1 transactivity in a gal11Delta yeast strain. These results
      suggest that there is functional conservation between Qr domains of yeast Gal11p
      and mammalian SRC proteins as direct targets of activator proteins in yeast.

PMID- 18070926
TI  - Role of WISP-2/CCN5 in the maintenance of a differentiated and noninvasive
      phenotype in human breast cancer cells.
AB  - WISP-2/CCN5 is an estrogen-regulated member of the "connective tissue growth
      factor/cysteine-rich 61/nephroblastoma overexpressed" (CCN) family of the cell
      growth and differentiation regulators. The WISP-2/CCN5 mRNA transcript is
      undetectable in normal human mammary cells, as well as in highly aggressive
      breast cancer cell lines, in contrast with its higher level in the breast cancer
      cell lines characterized by a more differentiated phenotype. We report here that
      knockdown of WISP-2/CCN5 by RNA interference in estrogen receptor alpha (ERalpha)
      positive MCF-7 breast cancer cells induced an estradiol-independent growth linked
      to a loss of ERalpha expression and promoted epithelial-to-mesenchymal
      transdifferentiation. In contrast, forced expression of WISP-2/CCN5 directed MCF
      7 cells toward a more differentiated phenotype. When introduced into the poorly
      differentiated, estrogen-independent, and invasive MDA-MB-231 breast cancer
      cells, WISP-2/CCN5 was able to reduce their proliferative and invasive
      phenotypes. In a series of ERalpha-positive tumor biopsies, we found a positive
      correlation between the expression of WISP-2/CCN5 and ID2, a transcriptional
      regulator of differentiation in normal and transformed breast cells. We propose
      that WISP-2/CCN5 is an important regulator involved in the maintenance of a
      differentiated phenotype in breast tumor epithelial cells and may play a role in
      tumor cell invasion and metastasis.

PMID- 18070927
TI  - P-TEFb is critical for the maturation of RNA polymerase II into productive
      elongation in vivo.
AB  - Positive transcription elongation factor b (P-TEFb) is the major metazoan RNA
      polymerase II (Pol II) carboxyl-terminal domain (CTD) Ser2 kinase, and its
      activity is believed to promote productive elongation and coupled RNA processing.
      Here, we demonstrate that P-TEFb is critical for the transition of Pol II into a
      mature transcription elongation complex in vivo. Within 3 min following P-TEFb
      inhibition, most polymerases were restricted to within 150 bp of the
      transcription initiation site of the active Drosophila melanogaster Hsp70 gene,
      and live-cell imaging demonstrated that these polymerases were stably associated.
      Polymerases already productively elongating at the time of P-TEFb inhibition,
      however, proceeded with elongation in the absence of active P-TEFb and cleared
      from the Hsp70 gene. Strikingly, all transcription factors tested (P-TEFb, Spt5,
      Spt6, and TFIIS) and RNA-processing factor CstF50 exited the body of the gene
      with kinetics indistinguishable from that of Pol II. An analysis of the
      phosphorylation state of Pol II upon the inhibition of P-TEFb also revealed no
      detectable CTD Ser2 phosphatase activity upstream of the Hsp70 polyadenylation
      site. In the continued presence of P-TEFb inhibitor, Pol II levels across the
      gene eventually recovered.

PMID- 18070928
TI  - Annexin A2 phosphorylation mediates cell scattering and branching morphogenesis
      via cofilin Activation.
AB  - Dynamic remodeling of the actin cytoskeleton is required for cell spreading,
      motility, and migration and can be regulated by tyrosine kinase activity.
      Phosphotyrosine proteomic screening revealed phosphorylation of the lipid-,
      calcium-, and actin-binding protein annexin A2 (AnxA2) at Tyr23 as a major event
      preceding ts-v-Src kinase-induced cell scattering. Expression of the phospho
      mimicking mutant Y23E-AnxA2 itself was sufficient to induce actin reorganization
      and cell scattering in MDCK cells. While Y23E-AnxA2, but not Y23A-AnxA2, enhanced
      Src- or hepatocyte growth factor (HGF)-induced cell scattering, short hairpin RNA
      mediated knockdown of AnxA2 inhibited both v-Src- and HGF-induced cell
      scattering. Three-dimensional branching morphogenesis was induced in wild-type
      AnxA2-expressing cells only in the presence of HGF, while Y23E-AnxA2 induced HGF
      independent branching morphogenesis. Knockdown of AnxA2 prevented lumen formation
      during cystogenesis. The Y23E-AnxA2-induced scattering was associated with
      dephosphorylation/activation of the actin-severing protein cofilin. Likewise,
      inactive S3E-cofilin and constitutively active LIM kinase, a direct upstream
      kinase of cofilin, inhibited Y23E-AnxA2-induced scattering. Together, our studies
      indicate an essential role for AnxA2 phosphorylation in regulating cofilin
      dependent actin cytoskeletal dynamics in the context of cell scattering and
      branching morphogenesis.

PMID- 18070929
TI  - A non-tumor suppressor role for basal p19ARF in maintaining nucleolar structure
      and function.
AB  - The nucleolus is the center of ribosome synthesis, with the nucleophosmin (NPM)
      and p19(ARF) proteins antagonizing one another to either promote or inhibit
      growth. However, basal NPM and ARF proteins form nucleolar complexes whose
      functions remain unknown. Nucleoli from Arf(-/)(-) cells displayed increased
      nucleolar area, suggesting that basal ARF might regulate key nucleolar functions.
      Concordantly, ribosome biogenesis and protein synthesis were dramatically
      elevated in the absence of Arf, causing these cells to exhibit tremendous gains
      in protein amounts and increases in cell volume. The transcription of ribosomal
      DNA (rDNA), the processing of nascent rRNA molecules, and the nuclear export of
      ribosomes were all increased in the absence of ARF. Similar results were obtained
      using targeted lentiviral RNA interference of ARF in wild-type MEFs. Postmitotic
      osteoclasts from Arf-null mice exhibited hyperactivity in vitro and in vivo,
      demonstrating a physiological function for basal ARF. Moreover, the knockdown of
      NPM blocked the increases in Arf(-/-) ribosome output and osteoclast activity,
      demonstrating that these gains require NPM. Thus, basal ARF proteins act as a
      monitor of steady-state ribosome biogenesis and growth independent of their
      ability to prevent unwarranted hyperproliferation.

PMID- 18070930
TI  - Insulin-like growth factor type-I receptor-dependent phosphorylation of
      extracellular signal-regulated kinase 1/2 but not Akt (protein kinase B) can be
      induced by picropodophyllin.
AB  - The initial event upon binding of insulin-like growth factor 1 to the insulin
      like growth factor type-I receptor (IGF-1R) is auto-phosphorylation of tyrosine
      residues within the activation loop of the kinase domain followed by
      phosphorylation of other receptor tyrosine residues and the subsequent activation
      of the intracellular signaling cascades. We found recently that the cyclolignan
      picropodophyllin (PPP) inhibits phosphorylation of IGF-1R and phosphatidyl-3
      kinase/Akt (protein kinase B) signaling molecules without interfering with the
      highly homologous insulin receptor. Furthermore, PPP causes regression of tumor
      grafts and substantially prolongs the survival of animals with systemic tumor
      disease. It is of interest that we show here that short treatments with PPP
      activate the intracellular extracellular signal-regulated kinase (ERK) signaling.
      Our data suggest that PPP induces IGF-1R ubiquitination and in turn activates
      ERK1/2. The PPP-induced ERK activation requires IGF-1R because PPP is not able to
      induce ERK phosphorylation in IGF-1R-negative cells or in cells in which the
      receptor is knocked down by small interfering RNA. Moreover, in the absence of
      Mdm2, an E3 ligase that has been shown previously to be involved in IGF-1R
      ubiquitination, the phosphorylation of ERK did not occur. Thus, apart from
      inhibiting the receptor activity, PPP can induce IGF-1R ubiquitination and
      stimulate ERK in an Mdm2-dependent manner. This response could contribute to the
      apoptotic effect of PPP.

PMID- 18070931
TI  - Assessment of the long-term safety of inhaled ciclesonide on growth in children
      with asthma.
AB  - OBJECTIVE: To assess the effects of the new inhaled corticosteroid ciclesonide on
      growth in children with asthma. METHODS: We performed a multicenter, randomized,
      double-blind, placebo-controlled study to assess the effects of inhaled
      ciclesonide on growth in children with mild, persistent asthma. After a 6-month
      run-in period, 661 prepubertal children who were aged 5.0 to 8.5 years were
      randomly assigned to once-daily morning treatment for 1 year with ciclesonide 40
      or 160 microg (ex-actuator) or placebo, followed by a 2-month follow-up period.
      The primary end point was the linear growth velocity (linear regression estimate)
      over the double-blind treatment period. Growth was recorded as the median of 4
      stadiometer measurements. Adverse events and 10-hour overnight and 24-hour
      urinary free cortisol levels were also assessed. RESULTS: Mean linear growth
      velocity during run-in was comparable between groups: 160 microg, 6.20 cm/year;
      40 microg, 6.59 cm/year; placebo, 6.49 cm/year. Mean differences from placebo
      (5.75 cm/year) in growth velocity over the double-blind treatment period were 
      0.02 cm/year for ciclesonide 40 microg and -0.15 cm/year for ciclesonide 160
      microg. Both ciclesonide treatments were noninferior to placebo with respect to
      growth velocity. The overall incidence of adverse events was comparable between
      groups, and no significant changes in 10-hour overnight or 24-hour urinary free
      cortisol levels were noted between groups during the double-blind treatment
      period. CONCLUSIONS: Ciclesonide demonstrated no detectable effect on childhood
      growth velocity, even at the highest dosage, which may ease concerns about
      systemic adverse events.

PMID- 18070932
TI  - Probability of walking in children with cerebral palsy in Europe.
AB  - OBJECTIVES: The purpose of this work was to describe walking ability in children
      with cerebral palsy from the Surveillance of Cerebral Palsy in Europe common
      database through 21 years and to examine the association between walking ability
      and predicting factors. PATIENTS AND METHODS: Anonymous data on 10042 children
      with cerebral palsy born between 1976 and 1996 were gathered from 14 European
      centers; 9012 patients were eligible for the analyses. RESULTS: Unaided walking
      as the primary way of walking at 5 years of age was reported for 54%, walking
      with assistive devices was reported for 16%, and no walking ability was reported
      for 30%. The proportion of children who were unable to walk was rather stable
      over time in all of the centers, with a mean proportion of 28%. Walking ability
      related significantly to cerebral palsy types, that is, spastic unilateral,
      spastic bilateral, dyskinetic, and ataxic cerebral palsy, as well as to IQ level,
      active epilepsy, and severe visual and hearing impairment. Severe cerebral palsy,
      defined as both the inability to walk and an IQ of <50, was present in 20% of the
      subjects. Logistic regression revealed that intellectual capacity was the
      variable most associated with walking ability in all 4 of the cerebral palsy
      types. The presence of a severe intellectual impairment increased the risk of
      being unable to walk 56 times if the child had unilateral spastic cerebral palsy
      type and 9 times if the child had bilateral spastic cerebral palsy type.
      CONCLUSIONS: The collaboration Surveillance of Cerebral Palsy in Europe provides
      a powerful means of monitoring trends in cerebral palsy and its functional
      consequences. The proportion of nonwalking in children with cerebral palsy seems
      to be rather stable over years and across centers despite the changes that have
      occurred in neonatal care across Europe. As is well known and also shown in this
      study, walking ability varied strongly with cerebral palsy type. Additional
      impairments, as well as the presence of epilepsy, correlated significantly with
      walking ability and, thus, the walking ability can be an indicator of total
      disability load.

PMID- 18070933
TI  - Noncanonical Wnt signaling promotes apoptosis in thymocyte development.
AB  - The Wnt-beta-catenin signaling pathway has been shown to govern T cell
      development by regulating the growth and survival of progenitor T cells and
      immature thymocytes. We explore the role of noncanonical, Wnt-Ca(2+) signaling in
      fetal T cell development by analyzing mice deficient for Wnt5a. Our findings
      reveal that Wnt5a produced in the thymic stromal epithelium does not alter the
      development of progenitor thymocytes, but regulates the survival of alphabeta
      lineage thymocytes. Loss of Wnt5a down-regulates Bax expression, promotes Bcl-2
      expression, and inhibits apoptosis of CD4(+)CD8(+) thymocytes, whereas exogenous
      Wnt5a increases apoptosis of fetal thymocytes in culture. Furthermore, Wnt5a
      overexpression increases apoptosis in T cells in vitro and increases protein
      kinase C (PKC) and calmodulin-dependent kinase II (CamKII) activity while
      inhibiting beta-catenin expression and activity. Conversely, Wnt5a deficiency
      results in the inhibition of PKC activation, decreased CamKII activity, and
      elevation of beta-catenin amounts in thymocytes. These results indicate that
      Wnt5a induction of the noncanonical Wnt-Ca(2+) pathway alters canonical Wnt
      signaling and is critical for normal T cell development.

PMID- 18070934
TI  - Role of host tissues for sustained humoral effects after endothelial progenitor
      cell transplantation into the ischemic heart.
AB  - Noncellular differentiation effects have emerged as important mechanisms
      mediating therapeutic effects of stem or progenitor cell transplantation. Here,
      we investigated the expression patterns and sources of humoral factors and their
      regional and systemic biological effects after bone marrow (BM)-derived
      endothelial progenitor cell (EPC) transplantation into ischemic myocardium.
      Although most of the transplanted EPCs disappeared within a week, up-regulation
      of multiple humoral factors was sustained for longer than two weeks, which
      correlated well with the recovery of cardiac function. To determine the source of
      the humoral factors, we injected human EPCs into immunodeficient mice. Whereas
      the expression of human EPC (donor)-derived cytokines rapidly decreased to a
      nondetectable level within a week, up-regulation of mouse (recipient)-derived
      cytokines, including factors that could mobilize BM cells, was sustained.
      Histologically, we observed higher capillary density, a higher proliferation of
      myocardial cells, a lower cardiomyocyte apoptosis, and reduced infarct size.
      Furthermore, after EPC transplantation, BM-derived stem or progenitor cells were
      increased in the peripheral circulation and incorporated into the site of
      neovascularization and myocardial repair. These data indicate that myocardial EPC
      transplantation induces humoral effects, which are sustained by host tissues and
      play a crucial role in repairing myocardial injury.

PMID- 18070935
TI  - A human postnatal lymphoid progenitor capable of circulating and seeding the
      thymus.
AB  - Identification of a thymus-seeding progenitor originating from human bone marrow
      (BM) constitutes a key milestone in understanding the mechanisms of T cell
      development and provides new potential for correcting T cell deficiencies. We
      report the characterization of a novel lymphoid-restricted subset, which is part
      of the lineage-negative CD34(+)CD10(+) progenitor population and which is
      distinct from B cell-committed precursors (in view of the absence of CD24
      expression). We demonstrate that these Lin(-)CD34(+)CD10(+)CD24(-) progenitors
      have a very low myeloid potential but can generate B, T, and natural killer
      lymphocytes and coexpress recombination activating gene 1, terminal
      deoxynucleotide transferase, PAX5, interleukin 7 receptor alpha, and CD3epsilon.
      These progenitors are present in the cord blood and in the BM but can also be
      found in the blood throughout life. Moreover, they belong to the most immature
      thymocyte population. Collectively, these findings unravel the existence of a
      postnatal lymphoid-polarized population that is capable of migrating from the BM
      to the thymus.

PMID- 18070936
TI  - Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4
      inflammasome.
AB  - Pseudomonas aeruginosa is a Gram-negative bacterium that causes opportunistic
      infections in immunocompromised individuals. P. aeruginosa employs a type III
      secretion system to inject effector molecules into the cytoplasm of the host
      cell. This interaction with the host cell leads to inflammatory responses that
      eventually result in cell death. We show that infection of macrophages with P.
      aeruginosa results in activation of caspase-1 in an IPAF-dependent, but flagellin
      independent, manner. Macrophages deficient in IPAF or caspase-1 were markedly
      resistant to P. aeruginosa-induced cell death and release of the proinflammatory
      cytokine interleukin (IL)-1beta. A subset of P. aeruginosa isolates express the
      effector molecule exoenzyme U (ExoU), which we demonstrate is capable of
      inhibiting caspase-1-driven proinflammatory cytokine production. This study shows
      a key role for IPAF and capase-1 in innate immune responses to the pathogen P.
      aeruginosa, and also demonstrates that virulent ExoU-expressing strains of P.
      aeruginosa can circumvent this innate immune response.

PMID- 18070937
TI  - Alu elements mediate MYB gene tandem duplication in human T-ALL.
AB  - Recent studies have demonstrated that the MYB oncogene is frequently duplicated
      in human T cell acute lymphoblastic leukemia (T-ALL). We find that the human MYB
      locus is flanked by 257-bp Alu repeats and that the duplication is mediated
      somatically by homologous recombination between the flanking Alu elements on
      sister chromatids. Nested long-range PCR analysis indicated a low frequency of
      homologous recombination leading to MYB tandem duplication in the peripheral
      blood mononuclear cells of approximately 50% of healthy individuals, none of whom
      had a MYB duplication in the germline. We conclude that Alu-mediated MYB tandem
      duplication occurs at low frequency during normal thymocyte development and is
      clonally selected during the molecular pathogenesis of human T-ALL.

PMID- 18070939
TI  - Dependence of antibody gene diversification on uracil excision.
AB  - Activation-induced deaminase (AID) catalyses deamination of deoxycytidine to
      deoxyuridine within immunoglobulin loci, triggering pathways of antibody
      diversification that are largely dependent on uracil-DNA glycosylase (uracil-N
      glycolase [UNG]). Surprisingly efficient class switch recombination is restored
      to ung(-/-) B cells through retroviral delivery of active-site mutants of UNG,
      stimulating discussion about the need for UNG's uracil-excision activity. In this
      study, however, we find that even with the overexpression achieved through
      retroviral delivery, switching is only mediated by UNG mutants that retain
      detectable excision activity, with this switching being especially dependent on
      MSH2. In contrast to their potentiation of switching, low-activity UNGs are
      relatively ineffective in restoring transversion mutations at C:G pairs during
      hypermutation, or in restoring gene conversion in stably transfected DT40 cells.
      The results indicate that UNG does, indeed, act through uracil excision, but
      suggest that, in the presence of MSH2, efficient switch recombination requires
      base excision at only a small proportion of the AID-generated uracils in the S
      region. Interestingly, enforced expression of thymine-DNA glycosylase (which can
      excise U from U:G mispairs) does not (unlike enforced UNG or SMUG1 expression)
      potentiate efficient switching, which is consistent with a need either for
      specific recruitment of the uracil-excision enzyme or for it to be active on
      single-stranded DNA.

PMID- 18070940
TI  - Beneficial effects of aggressive low-density lipoprotein cholesterol lowering in
      women with stable coronary heart disease in the Treating to New Targets (TNT)
      study.
AB  - OBJECTIVE: To examine by secondary analysis of the Treating to New Targets (TNT)
      study whether the benefits of intensive versus standard levels of lipid lowering
      are equally applicable to women. METHODS: A total of 10 001 patients (1902 women)
      with stable coronary heart disease (CHD) were randomised to double-blind
      treatment with atorvastatin 10 or 80 mg/day for a median follow-up of 4.9 years.
      RESULTS: In women and men, intensive treatment with atorvastatin 80 mg
      significantly reduced the rate of major cardiovascular events compared with
      atorvastatin 10 mg. Among women, the relative and absolute reductions were 27%
      and 2.7%, respectively (hazard ratio (HR) = 0.73, 95% confidence interval (CI)
      0.54 to 1.00, p = 0.049). In men, the corresponding rate reductions were 21% and
      2.2% (HR = 0.79, 95% CI 0.69 to 0.91, p = 0.001). The number needed to treat
      value (to prevent one cardiovascular event over 4.9 years compared with patients
      treated with atorvastatin 10 mg) for atorvastatin 80 mg was 29 for women and 30
      for men. Rates of death of non-cardiovascular origin in the atorvastatin 80 mg
      and atorvastatin 10 mg were 3.6% and 1.6%, respectively (p = 0.004) among women,
      and 2.8% and 3.1% (p = 0.47) among men. CONCLUSION: Intensive lipid-lowering
      treatment with atorvastatin 80 mg produced significant reductions in relative
      risk for major cardiovascular events compared with atorvastatin 10 mg in both
      women and men with stable CHD.

PMID- 18070938
TI  - Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor.
AB  - Viruses have evolved a myriad of evasion strategies focused on undermining
      chemokine-mediated immune surveillance, exemplified by the mouse gamma
      herpesvirus 68 M3 decoy receptor. Crystal structures of M3 in complex with C
      chemokine ligand 1/lymphotactin and CC chemokine ligand 2/monocyte
      chemoattractant protein 1 reveal that invariant chemokine features associated
      with G protein-coupled receptor binding are primarily recognized by the decoy C
      terminal domain, whereas the N-terminal domain (NTD) reconfigures to engage
      divergent basic residue clusters on the surface of chemokines. Favorable
      electrostatic forces dramatically enhance the association kinetics of chemokine
      binding by M3, with a primary role ascribed to acidic NTD regions that
      effectively mimic glycosaminoglycan interactions. Thus, M3 employs two distinct
      mechanisms of chemical imitation to potently sequester chemokines, thereby
      inhibiting chemokine receptor binding events as well as the formation of
      chemotactic gradients necessary for directed leukocyte trafficking.

PMID- 18070941
TI  - Predictors of in-hospital mortality for patients admitted with ST-elevation
      myocardial infarction: a real-world study using the Myocardial Infarction
      National Audit Project (MINAP) database.
AB  - OBJECTIVE: Although early thrombolysis reduces the risk of death in STEMI
      patients, mortality remains high. We evaluated factors predicting inpatient
      mortality for patients with STEMI in a "real-world" population. DESIGN: Analysis
      of the Myocardial Infarction National Audit Project (MINAP) database using
      multivariate logistic regression and area under the receiver operating curve
      analysis. SETTING: All acute hospitals in England and Wales. PATIENTS: 34 722
      patients with STEMI from 1 January 2003 to 31 March 2005. RESULTS: Inpatient
      mortality was 10.6%. The highest odds ratios for inpatient survival were aspirin
      therapy given acutely and out-of-hospital thrombolysis, independently associated
      with a mortality risk reduction of over half. A 10-year increase in age doubled
      inpatient mortality risk, whereas cerebrovascular disease increased it by 1.7.
      The risk model comprised 14 predictors of mortality, C index = 0.82 (95% CI 0.82
      to 0.83, p<0.001). A simple model comprising age, systolic blood pressure (SBP)
      and heart rate (HR) offered a C index of 0.80 (0.79 to 0.80, p<0.001).
      CONCLUSION: The strongest predictors of in-hospital survival for STEMI were
      aspirin therapy given acutely and out-of-hospital thrombolysis, Previous STEMI
      models have focused on age, SBP and HR We have confirmed the importance of these
      predictors in the discrimination of death after STEMI, but also demonstrated that
      other potentially modifiable variables impact upon the prediction of short-term
      mortality.

PMID- 18070942
TI  - Perception of symptoms is out of proportion to cardiac pathology in patients with
      "diastolic heart failure".
AB  - BACKGROUND: Epidemiological studies suggest that "diastolic heart failure" (DHF)
      is common and has a prognosis similar to that of systolic heart failure (SHF). We
      wanted to assess whether patients with breathlessness who were being treated for
      DHF had objective evidence of cardiac impairment and exercise limitation.
      METHODS: Consecutive patients with a clinical diagnosis of chronic heart failure
      completed a standardised 6-minute walk test (6-MWT) and underwent an
      echocardiographic examination to determine the presence of major structural heart
      disease (MSHD). N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured
      to determine degree of cardiac pathology. RESULTS: 568 patients were identified
      with SHF (75.7% males) and 104 with DHF (54.7% males). They were compared with
      400 healthy controls (matched with DHF group for age, sex and body mass index
      (BMI)). Controls (median (interquartile range); 43 (20-62) pmol/l)) and DHF
      patients (27 (13-67) pmol/l) had significantly lower NT-proBNP levels compared to
      SHF patients (178 (82-422) pmol/l). There was no difference in NT-proBNP levels
      between controls and DHF patients (p = 0.348). There was no correlation between
      BMI and NT-proBNP in either DHF (r(2) = 0.03; p = 0.287) or SHF (r(2) = 0.02; p =
      0.346) patients. Both SHF and DHF patients reported similar degrees of
      breathlessness. 6-MWT distance (p = 0.973) was similar between SHF and DHF
      patients. DHF patients had a higher BMI (p<0.0001). CONCLUSION: Patients being
      treated for a clinical diagnosis of DHF have the same self-reported symptoms and
      6-MWT performance as patients with SHF, yet have normal NT-proBNP levels. Their
      perception of their symptoms is out of proportion to their evidence of cardiac
      pathology.

PMID- 18070943
TI  - B-type natriuretic peptide predicts disease severity in children with
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: In adults with hypertrophic cardiomyopathy (HCM), plasma B-type
      natriuretic peptide (BNP) levels correlate with dyspnoea class and other markers
      of disease severity. In children with HCM, symptoms are a poor guide to disease
      severity and no studies have evaluated the clinical utility of BNP testing.
      OBJECTIVE: To assess the relation of BNP levels to symptoms and markers of
      disease severity in children with HCM. METHODS: Forty-four consecutive patients
      with HCM (27 male, age <or=17 years (median 13.6) underwent assessment of plasma
      BNP. Clinical evaluation of patients was carried out, including ECG,
      echocardiography and tissue Doppler imaging. RESULTS: BNP levels correlated with
      maximal left ventricular (LV) wall thickness (r(s) = 0.631, p<0.001), resting LV
      outflow tract gradient (r(s) = 0.611, p<0.001), transmitral E/septal Ea (E/Ea(s))
      ratio (r(s) = 0.770, p<0.001) and percentage predicted maximum VO(2) (r(s) = 
      0.390, p = 0.025); there was no relation between BNP and heart failure symptoms.
      BNP levels were higher in patients who had undergone implantation of an internal
      cardioverter-defibrillator than in those who had not (309 (interquartile range
      (IQR) 181-391) vs 50 (IQR 18-188) pg/ml, p = 0.001). BNP was independently
      associated with E/Ea(s) (r(s) = 0.632, p<0.001) and maximal LV wall thickness
      (r(s) = 0.412, p = 0.008) on multivariate analysis. At a cut-off point of 50
      pg/ml, BNP had a positive predictive value of 93% and a negative predictive value
      of 80% for predicting E/Ea(s) >10 (area under the receiver operator
      characteristic curve = 0.875 (p<0.001)). CONCLUSIONS: BNP levels correlate with
      non-invasive parameters of disease severity in children with HCM, including
      measures of raised LV filling pressures. For patients in whom evaluation of
      symptoms is difficult, BNP may be a useful additional tool in the assessment of
      disease severity.

PMID- 18070944
TI  - Do the extent and direction of arterial remodelling predict subsequent
      progression of coronary atherosclerosis? A serial intravascular ultrasound study.
AB  - OBJECTIVE: Despite the link between positive coronary remodelling and acute
      ischaemic events, no data exist about the impact of arterial remodelling on
      subsequent progression of coronary atherosclerosis. The objective of this study
      was to examine whether extent and direction of arterial remodelling are
      predictors of progression of coronary atherosclerosis. DESIGN, SETTING AND
      PATIENTS: From the Reversal of Atherosclerosis with Aggressive Lipid Lowering
      (REVERSAL) trial, 210 focal coronary lesions (single lesion per patient) were
      identified with <or=50% angiographic diameter stenosis at baseline intravascular
      ultrasound (IVUS). Remodelling was categorised using the remodelling index. MAIN
      OUTCOME MEASURES: Lesion sites were matched to the 18-month follow-up IVUS
      examination and change in atheroma area was calculated. Additionally, change in
      atheroma volume of the whole imaged artery was calculated. RESULTS: There were no
      relationships between baseline remodelling index and change in atheroma area at
      the lesion site (r = 0.004, p = 0.96) or change in atheroma volume in the whole
      artery (r = 0.06, p = 0.37). Change in atheroma area was not significantly
      different in lesions with positive, negative or no remodelling at baseline (0.4
      (SD 2.1) vs 0.7 (SD 1.7) vs 0.6 (SD 1.8) mm(2), p = 0.76). Similarly, change in
      atheroma volume in the whole artery was not significantly different among the
      three remodelling categories (2.2 (SD 25.0) vs 1.4 (SD 31.2) vs 2.4 (SD 27.1)
      mm(3), p = 0.98). CONCLUSIONS: Extent and direction of arterial remodelling do
      not predict subsequent progression of coronary atherosclerosis. Although
      positively remodelled lesions are associated with unstable clinical presentation,
      they are not associated with accelerated progression of atherosclerosis during
      lipid lowering therapy.

PMID- 18070945
TI  - Valve type and long-term outcomes after aortic valve replacement in older
      patients.
AB  - OBJECTIVE: To compare outcomes after aortic valve replacement (AVR) according to
      valve type specifically in older patients since valve-related risks are age
      dependent; two randomised trials comparing mechanical and bioprosthetic valves
      found better outcomes with mechanical valves, but the samples were small and the
      patients were considerably younger than most who undergo AVR. DESIGN: Cohort
      study. SETTING: 1199 US hospitals. PATIENTS: Patients 65 years and older
      undergoing AVR during 1991-2003 (n = 307 054) identified through Medicare claims
      data. MAIN OUTCOME MEASURES: Relative hazard ratios associated with bioprosthetic
      valves of (1) death (n = 131,719); (2) readmission for haemorrhage (n = 31,186),
      stroke (n = 25,051) or embolism (n = 5870); (3) reoperation (n = 4216); and (4)
      death or reoperation (reoperation free survival) in Cox regression analyses
      adjusting for demographic and clinical factors and hospital-level effects.
      RESULTS: Overall, 36% of AVR patients received bioprosthetic valves.
      Bioprosthetic valve recipients were older (77 vs 75 years, p<0.001) and generally
      had higher comorbidity. Bioprosthetic valve recipients had a slightly lower
      adjusted hazard ratios of death (HR = 0.97; 95% CI 0.95 to 0.98); readmission for
      haemorrhage, stroke or embolism (HR = 0.90, 95% CI 0.88 to 0.92); and death or
      reoperation (HR = 0.97, 95% CI 0.96 to 0.98), but a higher hazard ratio of
      reoperation (HR = 1.25, 95% CI 1.16 to 1.35). However, overall mortality and
      complication rates were more than 20 and 10 times higher, respectively, than the
      overall reoperation rate. CONCLUSIONS: In older patients undergoing AVR,
      bioprosthetic valve recipients had slightly lower risks of death and
      complications, but a higher risk of reoperation. Given the low reoperation rate,
      these data suggest that bioprosthetic valves may be preferred in older patients.

PMID- 18070946
TI  - Incidence of aortic valve regurgitation and outcome after percutaneous closure of
      atrial septal defects and patent foramen ovale.
AB  - BACKGROUND: In recent years percutaneous, transcatheter closure of atrial septal
      defects (ASD) or patent foramen ovale (PFO) was introduced into clinical
      practice. OBJECTIVE: To investigate the functional effects on heart valves caused
      by an interatrial closure device. METHODS AND RESULTS: Between 2001 and 2006, 240
      consecutive patients underwent percutaneous closure of an ASD or a PFO. Heart
      valve functions were defined by transoesophageal echocardiography before
      implantation and 3, 6 and 12 months after defect closure. A successful
      implantation procedure was performed in 98% of patients. Sufficient closure
      without residual shunt was achieved in 89% of patients with ASD and in 92% of
      patients with PFO. An overall major complication rate of 0.8% was apparent during
      the observation time (mean (SD) 27 (15) months). Long-term follow-up disclosed
      newly developed or worsened aortic valve regurgitation (AR) in 9% of patients
      with ASD and in 10% of patients with PFO. A potential cause for developing AR may
      be overgrowth of the device by tissue, leading to changes in interatrial septal
      geometry and traction on the root of the non-coronary aortic cusp. CONCLUSION: AR
      occurred in 9% of patients with closed ASD and in 10% of patients with closed
      PFO. Indication for closure should consider this potential complication despite
      an otherwise safe interventional procedure.

PMID- 18070948
TI  - Cooled ablation reduces pulmonary vein isolation time: results of a prospective
      randomised trial.
AB  - BACKGROUND: Currently, selection of the ablation catheter for pulmonary vein (PV)
      isolation is a matter of choice. OBJECTIVE: To evaluate the efficiency of cooled
      ablation for PV isolation. METHODS: A prospective randomised trial was carried
      out comparing the time required to disconnect each targeted PV using cooled
      ablation (open irrigation at 15 ml/min, group A) or standard temperature
      controlled 4 mm tip catheter ablation (group B). The ablation parameter limit
      settings were 45 degrees C, 35 (5) W in group A, and 55 degrees C, 35 (5) W in
      group B. RESULTS: Thirty-six patients referred for a first atrial fibrillation
      (AF) ablation procedure were randomised to group A or group B (18 patients in
      each group). There were no significant differences in baseline characteristics
      between the groups. Bidirectional block was achieved in 61/61 PVs from group A
      (100%) and 59/61 PVs from group B (97%); p = NS. Time to PV disconnection was
      significantly shorter in group A than in group B (median (25th-75th centiles) 14
      (5-28) min vs 19 (14-32) min, respectively; p = 0.003). Five asymptomatic PV
      stenoses were identified by MRI, all in group B (p = 0.05). After 1-year minimum
      follow-up, AF recurrences were less frequently documented in patients treated
      with cooled ablation (6% vs 33%; p = 0.05). CONCLUSION: Cooled ablation is more
      efficient than standard ablation in achieving PV isolation. Results obtained from
      this study also suggest a potential benefit of clinical efficacy and safety from
      cooled ablation, which should be further evaluated in larger clinical trials.

PMID- 18070947
TI  - Effects of stem cell therapy with G-CSF on coronary artery after drug-eluting
      stent implantation in patients with acute myocardial infarction.
AB  - OBJECTIVE: The effects of stem cell therapy on the coronary vasculature were
      investigated in patients with acute myocardial infarction who underwent
      peripheral blood stem cell (PBSC) therapy in the MAGIC Cell-3-DES study. METHODS:
      Among 50 patients with acute myocardial infarction who underwent either sirolimus
      eluting stent or paclitaxel-eluting stent implantation for the culprit lesion,
      intravascular ultrasound was analysed in 36 patients (cell infusion: n = 19 and
      control: n = 17). In the cell infusion group, PBSCs mobilised by granulocyte
      colony stimulating factor were delivered via intracoronary infusion into
      infarcted myocardium. Proximal and distal reference segments, and stented
      segments, were evaluated with intravascular ultrasound at immediate post
      intervention and 6-month follow-up, respectively. RESULTS: In the proximal and
      distal reference segments, the serial changes of lumen area, vessel area, and
      plaque plus media area were not significantly different between the cell infusion
      and the control groups. Within stented segments, mean neointimal area was similar
      in the two groups (cell infusion: 0.2 (SD 0.5) mm(2) vs control: 0.3 (SD 0.4)
      mm(2), p>0.05). However, there was a significant increase in mean peri-stent area
      of stented segment in the cell infusion group compared with the control group
      (0.7 (SD 1.4) mm(2) vs -0.1 (SD 1.2) mm(2), p<0.05). This difference mainly came
      from paclitaxel-eluting stent-implanted patients. CONCLUSION: Intracoronary
      infusion of PBSCs mobilised with G-CSF does not aggravate de novo atherosclerotic
      lesion and neointimal hyperplasia with DES implantation. However, it may induce
      peri-stent tissue growth at the stented segment, especially in patients receiving
      PES. Its clinical significance needs to be evaluated with long-term follow-up.

PMID- 18070949
TI  - Detection of inflammation in patients with acute aortic syndrome: comparison of
      FDG-PET/CT imaging and serological markers of inflammation.
AB  - OBJECTIVE: A substantial number of patients with acute aortic syndrome (AAS)
      require invasive therapy because of disease progression. Our study aimed to
      assess the impact of positron emission tomography (PET)/computed tomography (CT)
      and serological markers of inflammation to identify patients at high risk for
      disease progression. METHODS: 33 patients with AAS (thoracic aortic aneurysm 5,
      thoracic aortic dissection 14, penetrating aortic ulcer 8, intramural haematoma
      6) were included. After intravenous administration of [18F] fluorodeoxyglucose a
      non-contrast enhanced PET/CT of the body trunk and CT angiography of the entire
      aorta was performed. Serological levels of D-dimers and C-reactive protein (CRP)
      were measured in all patients. Follow-up imaging was performed to detect disease
      progression. RESULTS: 11 (33%) of 33 patients showed elevated tracer uptake
      within the aortic pathology, whereas 22 patients were PET-negative. In 23
      patients a CRP level exceeding 1.0 mg/dl or a D-dimer level larger than 250
      microg/l was found. The follow-up time was 224 (195) days. Nine of 11 PET
      positive patients (82%) showed progression of AAS. In contrast, 55% of PET
      negative patients showed stable disease or regression during the follow-up
      period. Kaplan-Meier analysis showed a clear, but not yet significant trend to
      longer survival in PET-negative patients, whereas elevated CRP and D-dimers did
      not allow for distinguishing of high-risk patients. CONCLUSIONS: Vessel wall
      inflammation was found in one-third of the patients with AAS and this patient
      group seems to have a high risk for disease progression. These initial results
      needs further investigation.

PMID- 18070950
TI  - Homocysteine, migration and early vascular impairment in people of African
      descent.
AB  - OBJECTIVES: A gradient of increased vascular risk with migration exists across
      the African diaspora. We investigated the hypothesis that differences in
      homocysteine/folic acid status contribute to this increased risk. DESIGN:
      Community cohort study of 73 Afro-Caribbeans in the United Kingdom and 151
      matched Afro-Caribbeans in Jamaica with no conventional vascular risk factors.
      METHODS: Subjects were compared for baseline characteristics, vascular risk
      profile, homocysteine (tHcy), folate and B(12) concentrations. Endothelium
      dependent vasodilatation was assessed by measuring the absolute change from
      baseline in the reflection index (RI) of the digital volume pulse during
      intravenous infusion of albuterol (5 microg/min, Delta RI(ALB)) and
      glyceryltrinitrate (GTN) (5 microg/min, Delta RI(GTN)). Carotid intima media
      thickness (CIMT) was measured ultrasonographically in the distal 1 cm of the
      common carotid artery. RESULTS: UK Afro-Caribbeans had higher tHcy (mean
      difference 2.3 (95% confidence interval 1.3 to 3.4) micromol/l) and lower folate
      (mean difference 3.2 (95% CI 1.8 to 4.7) microg/l) levels. Delta RI(ALB) was 5.1
      (95% CI 2.5 to 7.6) percentage points lower and CIMT 0.124 (95% CI 0.075 to
      0.173) mm greater in UK Afro-Caribbeans. Higher tHcy and lower folate
      concentrations correlated with impaired Delta RI(ALB) and increased CIMT. A 1
      microg/l increase in folate concentration was associated with 0.3 (95% CI 0.1 to
      0.5) percentage point increase in Delta RI(ALB) and 0.002 (95% CI 0.001 to 0.006)
      mm decrease in CIMT, independent of blood pressure, smoking and vascular risk
      profile. CONCLUSIONS: Lower folate concentrations in UK compared with West Indian
      African-Caribbeans may contribute to the higher stroke risk seen in UK African
      Caribbean people.

PMID- 18070951
TI  - A brief cognitive behavioural preimplantation and rehabilitation programme for
      patients receiving an implantable cardioverter-defibrillator improves physical
      health and reduces psychological morbidity and unplanned readmissions.
AB  - OBJECTIVE: To assess the clinical and cost effectiveness of a brief home-based
      cognitive behavioural rehabilitation programme (the ICD Plan) for patients
      undergoing implantation of a cardiac defibrillator. DESIGN: A prospective
      multicentred, intention-to-treat, cluster-randomised controlled trial. SETTING:
      Eight implantable cardioverter-defibrillator (ICD) implantation centres in the
      UK. PATIENTS: Consecutive series of patients undergoing implantation with an ICD.
      INTERVENTIONS: The control group received usual care and advice from an
      experienced healthcare professional. The intervention group received usual care
      plus the ICD Plan. The plan was introduced before implantation, with three
      further brief telephone contacts with the nurse over the next 12 weeks. MAIN
      OUTCOME MEASURES: Health-related quality of life (Short Form Health Survey (SF
      12)), anxiety and depression (Hospital Anxiety and Depression Scale (HADS)),
      activity limitations (subscale from the Seattle Angina Questionnaire (SAQ)),
      unplanned admissions and other economic data using a questionnaire developed for
      the study. RESULTS: 192 patients were recruited to the study (71 intervention,
      121 control). At 6 months after surgery the intervention group had better
      physical health (37.83 vs 34.24; p<0.01), fewer limitations in physical activity
      (34.02 vs 31.72; p = 0.04), a greater reduction in the proportion of patients
      with a borderline diagnosis of anxiety (21% vs 13%; p = 0.60) and depression (13%
      vs 2%; p = 0.30), more planned ECGs (89% vs 66%; p = 0.04) and 50% fewer
      unplanned admissions (11% vs 22%; p<0.01). CONCLUSIONS: The ICD Plan improved
      health-related quality of life, reduced the incidence of clinically significant
      psychological distress and significantly reduced unplanned readmissions. It is a
      cost effective and easily implemented method for delivering rehabilitation and
      psychological care to patients undergoing ICD implantation. TRIAL REGISTRATION
      NUMBER: ISRCTN70212111.

PMID- 18070952
TI  - Subacute cardiac toxicity following autologous haematopoietic stem cell
      transplantation in patients with normal cardiac function.
AB  - OBJECTIVE: To investigate subacute cardiac toxicity in patients with normal
      baseline cardiac function following autologous haematopoietic stem cell
      transplantation. DESIGN: Prospective observational study. PATIENT AND METHODS:
      Thirty-two consecutive patients (mean (SD) age 60 (11) years) with normal left
      ventricular ejection fraction (LVEF >or=50%) undergoing autologous haematopoietic
      stem cell transplantation were studied. Transthoracic echocardiography (including
      colour tissue Doppler imaging-derived myocardial velocities, strain and strain
      rates), troponin-T and B-type natriuretic peptide (BNP) and clinical details were
      recorded at baseline, after conditioning chemotherapy and serially over 6 weeks
      from the day of transplantation. RESULTS: The mean (SD) LVEF at baseline was 62
      (6)% and decreased to 55 (16)%, 6 weeks after transplantation (p = 0.007).
      Cardiac toxicity (>or=10% absolute decline of LVEF to an LVEF <or=50%) developed
      in 10 (31%) patients within 17 (8) days of transplantation and was usually
      reversible. In these 10 patients, the nadir LVEF was 39 (12)%. Two patients
      developed severe clinical pulmonary oedema, one episode of which was fatal.
      Troponin-T was mildly raised in only three of the patients with cardiac toxicity.
      Peak BNP values were similar in patients with or without post-transplant cardiac
      toxicity (149 (100) vs 196 (178) pg/ml, p = 0.43). Multivariate Cox proportional
      hazard regression identified baseline mitral annular systolic velocity as the
      only independent predictor of cardiac toxicity (hazard ratio 0.42, 95% confidence
      interval 0.20 to 0.86, p = 0.02). CONCLUSION: Subacute cardiac toxicity is common
      after autologous haematopoietic stem cell transplantation, even in patients with
      apparently normal left ventricular function. Anticipation of the period of
      greatest risk and recognition of patients with subclinical myocardial dysfunction
      may prevent clinical heart failure.

PMID- 18070953
TI  - Infarct size by contrast enhanced cardiac magnetic resonance is a stronger
      predictor of outcomes than left ventricular ejection fraction or end-systolic
      volume index: prospective cohort study.
AB  - OBJECTIVES: Ejection fraction (EF) and end-systolic volume index (ESVI) are
      established predictors of outcomes following ST-segment elevation myocardial
      infarction (STEMI). We sought to assess the relative impact of infarct size, EF
      and ESVI on clinical outcomes and left ventricular (LV) remodelling. DESIGN:
      Prospective cohort study. SETTING: Academic hospital in Chicago, USA. PATIENTS:
      122 patients with STEMI following acute percutaneous reperfusion. MAIN OUTCOME
      MEASURES: Death, recurrent myocardial infarction (MI) and heart failure. METHODS:
      Cardiac magnetic resonance imaging was obtained within 1 week following STEMI in
      122 subjects. ESVI, EF and infarct size were tested for the association with
      outcomes over 2 years in 113 subjects, and a repeat study was obtained 4 months
      later to assess LV remodelling in 91 subjects. RESULTS: Acute infarct size
      correlated linearly with the initial ESVI (r = 0.69, p<0.001), end-diastolic
      volume index (EDVI) (r = 0.42, p<0.001) and EF (r = -0.75, p<0.001). All were
      independently associated with outcomes (one death, one recurrent MI and 16 heart
      failure admissions). However, infarct size was the only significant predictor of
      adverse outcomes (p<0.05) by multivariate analysis. The smallest infarct size
      tertile had an increased EF (49% (SD 8%) to 53% (6%); p = 0.002) and unchanged
      EDVI (p = 0.7). In contrast, subjects with the largest infarct tertile also had
      improved EF (32% (9%) to 36% (11%); p = 0.002) at the expense of a dramatic
      increase in EDVI (86 (19) to 95 (21) ml/m(2); p = 0.005). CONCLUSIONS: Infarct
      size, EF and ESVI can predict the development of future cardiac events. Acute
      infarct size, which is independent of LV stunning and loading, directly relates
      to LV remodelling and is a stronger predictor of future events than measures of
      LV systolic performance.

PMID- 18070954
TI  - In vitro resistance study of AG-021541, a novel nonnucleoside inhibitor of the
      hepatitis C virus RNA-dependent RNA polymerase.
AB  - A novel class of nonnucleoside hepatitis C virus (HCV) polymerase inhibitors
      characterized by a dihydropyrone core was identified by high-throughput
      screening. Crystallographic studies of these compounds in complex with the
      polymerase identified an allosteric binding site close to the junction of the
      thumb and finger domains, approximately 30 A away from the catalytic center. AG
      021541, a representative compound from this series, displayed measurable in vitro
      antiviral activity against the HCV genotype 1b subgenomic replicon with a mean
      50% effective concentration of 2.9 muM. To identify mutations conferring in vitro
      resistance to AG-021541, resistance selection was carried out using HCV replicon
      cells either by serial passages in increasing concentrations of AG-021541 or by
      direct colony formation at fixed concentrations of the compound. We identified
      several amino acid substitutions in the AG-021541-binding region of the
      polymerase, including M423(T/V/I), M426T, I482(S/T), and V494A, with M423T as the
      predominant change observed. These mutants conferred various levels of resistance
      to AG-021541 and structurally related compounds but remained sensitive to
      interferon and HCV polymerase inhibitors known to interact with the active site
      or other allosteric sites of the protein. In addition, dihydropyrone polymerase
      inhibitors retained activity against replicons that contain signature resistance
      changes to other polymerase inhibitors, including S282T, C316N, M414T, and
      P495(S/L), indicating their potential to be used in combination therapies with
      these polymerase inhibitors. AG-021541-resistant replicon cell lines provide a
      valuable tool for mechanism-of-action studies of dihydropyrone polymerase
      inhibitors. The clinical relevance of in vitro resistance to HCV polymerase
      inhibitors remains to be investigated.

PMID- 18070955
TI  - Combined real-time PCR and pyrosequencing strategy for objective, sensitive,
      specific, and high-throughput identification of reduced susceptibility to
      penicillins in Neisseria meningitidis.
AB  - A segment of penA in Neisseria meningitidis strains (n = 127), including two
      nucleotide sites closely associated to reduced susceptibility to penicillins, was
      amplified and pyrosequenced. All results were in concordance with Sanger
      sequencing, and a high correlation between alterations in the two Pen(i)-specific
      sites and reduced susceptibility to penicillins was identified.

PMID- 18070956
TI  - In vitro antimycobacterial activities of capuramycin analogues.
AB  - Translocase I inhibitor compounds derived from capuramycin demonstrated rapid
      bactericidal activity against several different mycobacterial species. SQ641 was
      the most active of the compounds, with a MIC of 0.12 to 8 microg/ml, a
      postantibiotic effect of 55 h, and interesting synergistic effects with other
      antitubercular drugs.

PMID- 18070957
TI  - New genetic element carrying the erythromycin resistance determinant erm(TR) in
      Streptococcus pneumoniae.
AB  - erm(A) subclass erm(TR), a common macrolide resistance determinant in
      Streptococcus pyogenes but quite rare in Streptococcus pneumoniae, was found in a
      clinical S. pneumoniae isolate (AP200) from Italy. In this isolate, erm(TR) was
      found included in a genetic element approximately 56 kb in size that did not
      appear to be conjugative but could be transferred by transformation. An erm(TR)
      containing DNA fragment of approximately 10 kb was sequenced and 12 open reading
      frames (ORFs) were identified. Upstream of erm(TR), a regulatory protein of the
      TetR family and the two components of an efflux pump of the ABC type were found.
      Downstream of erm(TR), there were ORFs homologous to a spectinomycin
      phosphotransferase, transposases, and a relaxase. Since the genomic sequence of
      S. pyogenes MGAS10750 carrying erm(TR) became available, comparison between the
      erm(TR)-containing genetic elements in AP200 and in MGAS10750 was performed. The
      region flanking erm(TR) in MGAS10750 showed identity with AP200 for 10 ORFs out
      of 12. PCR mapping using primers designed on the sequence of MGAS10750 confirmed
      that AP200 carries a genetic element similar to that of MGAS10750. In AP200 the
      genetic element was inserted inside an ORF homologous to spr0790 of S. pneumoniae
      R6, coding for a type I restriction modification system. Homologies between the
      insertion sites in AP200 and MGAS10750 consisted of eight conserved nucleotides,
      of which three were duplicated, likely representing target site duplication. The
      structure of the erm(TR)-carrying genetic element shows characteristics of a
      transposon/prophage remnant chimera. In AP200 this genetic element was designated
      Tn1806.

PMID- 18070958
TI  - In vitro activities of doripenem and six comparator drugs against 423 aerobic and
      anaerobic bacterial isolates from infected diabetic foot wounds.
AB  - Against 182 anaerobe and 241 aerobe strains obtained from diabetic foot
      infections, doripenem was the most active carbapenem against Pseudomonas
      aeruginosa (MIC(90), 2 microg/ml), more active than imipenem against Proteus
      mirabilis, and ertapenem was more active against Escherichia coli and Klebsiella
      spp. The MIC(50) and MIC(90) values were < or =0.125 microg/ml for methicillin
      sensitive Staphylococcus aureus and all streptococci and 0.25/1 for Bacteroides
      fragilis.

PMID- 18070959
TI  - Complete DNA sequence and analysis of the transferable multiple-drug resistance
      plasmids (R Plasmids) from Photobacterium damselae subsp. piscicida isolates
      collected in Japan and the United States.
AB  - Photobacterium damselae subsp. piscicida is a bacterial fish pathogen that causes
      a disease known as pasteurellosis. Two transferable multiple-drug resistance (R)
      plasmids, pP99-018 (carrying resistance to kanamycin, chloramphenicol,
      tetracycline, and sulfonamide) and pP91278 (carrying resistance to tetracycline,
      trimethoprim, and sulfonamide), isolated from P. damselae subsp. piscicida
      strains from Japan (P99-018) and the United States (P91278), respectively, were
      completely sequenced and analyzed, along with the multiple-drug resistance
      regions of three other R plasmids also from P. damselae subsp. piscicida strains
      from Japan. The sequence structures of pP99-018 (150,057 bp) and pP91278 (131,520
      bp) were highly conserved, with differences due to variation in the drug
      resistance and conjugative transfer regions. These plasmids, shown to be closely
      related to the IncJ element R391 (a conjugative, self-transmitting, integrating
      element, or constin), were divided into the conjugative transfer, replication,
      partition, and multiple-drug resistance regions. Each of the five multiple-drug
      resistance regions sequenced exhibited unique drug resistance marker composition
      and arrangement.

PMID- 18070960
TI  - Antimicrobial activities of tigecycline and other broad-spectrum antimicrobials
      tested against serine carbapenemase- and metallo-beta-lactamase-producing
      Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program.
AB  - A total of 104 carbapenemase (serine- and metallo-beta-lactamase [MbetaL])
      producing strains of the Enterobacteriaceae family collected from 2000 to 2005 in
      medical centers distributed worldwide were tested against tigecycline and 25
      comparators by reference broth microdilution methods. The most frequent
      carbapenemase was KPC-2 or -3 (73 strains), followed by VIM-1 (14), IMP-1 (11),
      SME-2 (5), and NMC-A (1). All serine carbapenemases were detected in the United
      States, while MbetaL-producing strains were isolated in Europe. Carbapenemase
      producing Enterobacteriaceae showed high rates of resistance to most
      antimicrobial agents tested. The rank order of in vitro activity against these
      strains was as follows: tigecycline (100.0% susceptible) > polymyxin B (88.1%) >
      amikacin (73.0%) > imipenem (37.5%). Tigecycline was very active (MIC(90), 1
      microg/ml) against this significant, contemporary collection of well
      characterized strains and appears to be an excellent option compared to the
      polymyxins for treatment of infections caused by these multidrug-resistant
      Enterobacteriaceae.

PMID- 18070961
TI  - Clinical and economic impact of common multidrug-resistant gram-negative bacilli.

PMID- 18070963
TI  - Tetracycline resistance gene tet(W) in the pathogenic bacterium Clostridium
      difficile.
AB  - In this study, the tet(W) gene region of a human clinical isolate of Clostridium
      difficile resistant to tetracycline was characterized. This gene was a new allele
      showing 99% sequence identity to the gene found in the human strain
      Bifidobacterium longum F8, and it is not transferable by "in vitro" mating
      experiments.

PMID- 18070962
TI  - Replication of Colonic Crohn's Disease Mucosal Escherichia coli Isolates within
      Macrophages and Their Susceptibility to Antibiotics.
AB  - There is increasing evidence that Escherichia coli organisms are important in
      Crohn's disease (CD) pathogenesis. In CD tissue they are found within
      macrophages, and the adherent-invasive CD ileal E. coli isolate LF82 can
      replicate inside macrophage phagolysosomes. This study investigates replication
      and antibiotic susceptibility of CD colonic E. coli isolates inside macrophages.
      Replication of CD colonic E. coli within J774-A1 murine macrophages and human
      monocyte-derived macrophages (HMDM) was assessed by culture and lysis after
      gentamicin killing of noninternalized bacteria and verified by electron
      microscopy (EM). All seven CD colonic isolates tested replicated within J774-A1
      macrophages by 3 h (6.36-fold +/- 0.7-fold increase; n = 7 isolates) to a similar
      extent to CD ileal E. coli LF82 (6.8-fold +/- 0.8-fold) but significantly more
      than control patient isolates (5.2-fold +/- 0.25-fold; n = 6; P = 0.006) and E.
      coli K-12 (1.0-fold +/- 0.1-fold; P < 0.0001). Replication of CD E. coli HM605
      within HMDM (3.9-fold +/- 0.7-fold) exceeded that for K-12 (1.4-fold +/- 0.2
      fold; P = 0.03). EM showed replicating E. coli within macrophage vacuoles.
      Killing of HM605 within J774-A1 macrophages following a 3-h incubation with
      antibiotics at published peak serum concentrations (C(max)) was as follows: for
      ciprofloxacin, 99.5% +/- 0.2%; rifampin, 85.1% +/- 6.6%; tetracycline, 62.8% +/-
      6.1%; clarithromycin, 62.1% +/- 5.6% (all P < 0.0001); sulfamethoxazole, 61.3% +/
      7.0% (P = 0.0007); trimethoprim, 56.3% +/- 3.4% (P < 0.0001); and azithromycin,
      41.0% +/- 10.5% (P = 0.03). Ampicillin was not effective against intracellular E.
      coli. Triple antibiotic combinations were assessed at 10% C(max), with
      ciprofloxacin, tetracycline, and trimethoprim causing 97% +/- 0.0% killing versus
      86% +/- 2.0% for ciprofloxacin alone. Colonic mucosa-associated E. coli,
      particularly CD isolates, replicate within macrophages. Clinical trials are
      indicated to assess the efficacy of a combination antibiotic therapy targeting
      intramacrophage E. coli.

PMID- 18070964
TI  - Azurin-like protein blocks invasion of Toxoplasma gondii through potential
      interactions with parasite surface antigen SAG1.
AB  - Some pathogenic bacteria produce factors that have evolved a capacity to
      neutralize competing microbes. The cupredoxin family protein azurin, produced by
      Pseudomonas aeruginosa, exhibits a remarkable ability to impede invasion of a
      number of diverse intracellular pathogens, including the human AIDS virus human
      immunodeficiency virus type 1 and the protozoan parasite Plasmodium falciparum
      (which causes malaria). Here we report that azurin and an azurin-like protein
      (Laz) from gonococci/meningococci have activity against Toxoplasma, an
      apicomplexan parasite that causes opportunistic infection in immunocompromised
      individuals. We demonstrate that the mechanism of action for Laz involves
      interfering with the ability of Toxoplasma to adhere to host cells. Computer
      structural analysis reveals that azurin shares structural features with the
      predominant surface antigen SAG1, which is known to play an important role in
      parasite attachment. Interestingly, azurin also has structural similarities to a
      monoclonal antibody to SAG1. Surface plasmon resonance binding studies validate
      that SAG1 interacts strongly with Laz and, to lesser extent, azurin. Moreover,
      Toxoplasma mutants lacking SAG1 are not as susceptible to the growth-inhibitory
      effects of Laz. Collectively, our data show that Toxoplasma adhesion can be
      significantly impaired by Laz, and to some extent by azurin, via interactions
      with SAG1. These observations indicate that Laz can serve as an important tool in
      the study of host-pathogen interactions and is worthy of further study for
      development into potential therapeutic agents.

PMID- 18070965
TI  - Molecular basis for resistance of acanthamoeba tubulins to all major classes of
      antitubulin compounds.
AB  - Tubulin is essential to eukaryotic cells and is targeted by several
      antineoplastics, herbicides, and antimicrobials. We demonstrate that Acanthamoeba
      spp. are resistant to five antimicrotubule compounds, unlike any other eukaryote
      studied so far. Resistance correlates with critical amino acid differences within
      the inhibitor binding sites of the tubulin heterodimers.

PMID- 18070966
TI  - Staphylococcus aureus clinical isolate with high-level methicillin resistance
      with an lytH mutation caused by IS1182 insertion.
AB  - We previously reported that deficiency of the lytH gene, whose product is
      homologous to lytic enzymes, caused the elevation of methicillin resistance in
      Staphylococcus aureus strain SR17238, a strain of S. aureus with a low level of
      resistance to methicillin (low-level MRSA) (J. Bacteriol. 179:6294-6301, 1997).
      In this study, we demonstrated that deficiency of lytH caused the same phenomenon
      in four other clinical isolates of low-level MRSA, suggesting this deficiency to
      exist in clinical isolates. We therefore searched the region including lytH in
      127 clinical isolates of MRSA by PCR and found one strain, SR17164 (methicillin
      MIC, 1,600 microg/ml), in which the lytH gene was inactivated by insertion
      sequence IS1182. lytH::IS1182 was replaced with intact lytH in this strain by
      integration and excision of the plasmid carrying the lytH region. Recombinants
      with intact lytH genes showed methicillin MICs of 800 microg/ml, twofold lower
      than those of the recombinants with lytH::IS1182 and the parent. In addition, S.
      aureus SR17164, which has a high level of methicillin resistance, had properties
      similar to those caused by lytH deficiency; that is, the resistance levels of
      strain SR17164 and lytH-deficient variants from strain SR17238 were not
      significantly affected by llm inactivation, which greatly lowered resistance
      levels in most other high-level MRSA strains. These findings suggest that lytH
      inactivation contributed, to some extent, to the resistance level of S. aureus
      SR17164. To the best of our knowledge, this strain is the first clinical isolate
      of MRSA for which the genetic base for high-level resistance has been clarified.

PMID- 18070967
TI  - Hepatotoxicity observed in clinical trials of aplaviroc (GW873140).
AB  - Aplaviroc (APL) was a new CCR5 antagonist that was investigated in two dose
      ranging studies with antiretroviral therapy-naive, human immunodeficiency virus
      infected adults: ASCENT, in which 147 subjects were randomized 2:2:1 to receive
      zidovudine-lamivudine (ZDV-3TC) plus APL 600 mg twice a day (BID), APL 800 mg
      BID, or efavirenz (EFV), respectively, and EPIC, in which 195 subjects were
      randomized 2:2:2:1 to receive lopinavir-ritonavir (LPV-RTV) plus APL 200 mg BID,
      APL 400 mg BID, APL 800 mg once a day, or ZDV-3TC BID, respectively. Both studies
      (and, ultimately, the clinical development of APL) were discontinued after a mean
      of 14 weeks of therapy because of higher than anticipated severe liver toxicity;
      grade 2 or higher treatment-emergent elevations in alanine aminotransferase (ALT)
      levels were observed in 17/281 (6.0%) APL recipients but only 2/55 (3.6%) control
      recipients, while grade 2 or higher elevations in total bilirubin levels occurred
      in 29/281 (10.3%) APL recipients but only 4/55 (7.3%) controls. Two APL
      recipients developed grade 3 or higher treatment-emergent elevations in both ALT
      and total bilirubin levels, and one of these individuals had a severe case of
      hepatic cytolysis that was attributed to APL. Despite the high intersubject
      variability in APL plasma exposures, a Pearson correlation analysis of the
      combined study data did not reveal any significant associations between plasma
      concentrations and the liver enzyme elevations observed during the study. The
      mechanism for the idiosyncratic hepatotoxicity observed in the clinical trials of
      APL is unknown but is likely intrinsic to the molecule rather than its novel
      mechanism of action.

PMID- 18070968
TI  - Prevalence of and molecular basis for tuberculosis drug resistance in the
      Republic of Georgia: validation of a QIAplex system for detection of drug
      resistance-related mutations.
AB  - We developed a QIAplex system for the simultaneous detection of 24 Mycobacterium
      tuberculosis gene mutations responsible for resistance to isoniazid (INH),
      rifampin (RIF), streptomycin (STM), and ethambutol (EMB) in 196 M. tuberculosis
      isolates recovered in the Republic of Georgia. In comparison to phenotypic
      susceptibility tests, the QIAplex showed sensitivity and specificity of 85.4% and
      96.1% for INH, 94.4% and 99.4% for RIF, 69.6% and 99.2% for STM, 50.0% and 98.8%
      for EBM, and 86.7% and 100.0% for multidrug resistance, respectively. The
      dominant resistance mutations revealed were a mutation in katG resulting in S315T
      (katG S315T), rpsL K43R, and rpoB S531L. Mutations katG S315G and S315T and rpoB
      S531L were detected with higher frequencies in pretreated patients than in naive
      patients (P < 0.05). Simultaneous detection of 24 common drug resistance-related
      mutations provides a molecular tool for studying and monitoring M. tuberculosis
      resistance mechanism and epidemiology.

PMID- 18070969
TI  - Modulation of gene expression in human macrophages treated with the anti
      leishmania pentavalent antimonial drug sodium stibogluconate.
AB  - Within the mammalian host, Leishmania donovani is an obligatory intracellular
      protozoan parasite that resides and multiplies exclusively in the phagolysosomes
      of macrophages. Leishmania control relies primarily on chemotherapy, with the
      mainstay being pentavalent antimony (SbV) complexed to carbohydrates in the form
      of sodium stibogluconate (Pentostam) or meglumine antimoniate (Glucantime). The
      mode of action of SbV is still not known precisely. To explore the effect of SbV
      on macrophage gene expression, a microarray analysis was performed using
      Affymetrix focus arrays to compare gene expression profiles in noninfected and L.
      donovani-infected THP-1 monocytic cells treated or not treated with sodium
      stibogluconate. Under our experimental conditions, SbV changed the expression of
      a few host genes, and this was independent of whether cells were infected or not
      infected with Leishmania. Leishmania infection had a greater effect on the
      modulation of host gene expression. Statistical analyses have indicated that the
      expression of eight genes was modified by at least twofold upon SbV treatment,
      with six genes upregulated and two genes downregulated. One gene whose expression
      was affected by SbV was the heme oxygenase gene HMOX-1, and this change was
      observed both in the monocytic cell line THP-1 and in primary human monocyte
      derived macrophages. Another pathway that was affected was the glutathione
      biosynthesis pathway, where the expression of the glutamate-cysteine ligase
      modifier subunit was increased upon SbV treatment. Our analysis has suggested
      that, under our experimental conditions, the expression of a few genes is altered
      upon SbV treatment, and some of these encoded proteins may be implicated in the
      yet-to-be-defined mode of action of SbV.

PMID- 18070970
TI  - Intracellular efavirenz levels in peripheral blood mononuclear cells from human
      immunodeficiency virus-infected individuals.
AB  - We describe a novel method for isolating plasma-free peripheral blood mononuclear
      cells retaining intracellular efavirenz. Quantification of efavirenz in 13 human
      immunodeficiency virus-infected patients by liquid chromatography-tandem mass
      spectrometry showed a higher correlation of intracellular levels with unbound
      plasma levels (accumulation ratio, 1,190) than with total plasma levels.

PMID- 18070971
TI  - Thiopurine drugs azathioprine and 6-mercaptopurine inhibit Mycobacterium
      paratuberculosis growth in vitro.
AB  - The in vitro susceptibility of human- and bovine-origin Mycobacterium
      paratuberculosis to the thioupurine drugs 6-mercaptopurine (6-MP) and
      azathioprine (AZA) was established using conventional plate counting methods and
      the MGIT 960 ParaTB culture system. Both 6-MP and AZA had antibacterial activity
      against M. paratuberculosis; isolates from Crohn's disease patients tended to be
      more susceptible than were bovine-origin isolates. Isolates of Mycobacterium
      avium, used as controls, were generally resistant to both AZA and 6-MP, even at
      high concentrations (> or =64.0 microg/ml). Among rapidly growing mycobacteria,
      Mycobacterium phlei was susceptible to 6-MP and AZA whereas Mycobacterium
      smegmatis strains were not. AZA and 6-MP limited the growth of, but did not kill,
      M. paratuberculosis in a dose-dependent manner. Anti-inflammatory drugs in the
      sulfonamide family (sulfapyridine, sulfasalazine, and 5-aminosalycilic acid
      [mesalamine]) had little or no antibacterial activity against M.
      paratuberculosis. The conventional antibiotics azithromycin and ciprofloxacin,
      used as control drugs, were bactericidal for M. paratuberculosis, exerting their
      killing effects on the organism relatively quickly. Simultaneous exposure of M.
      paratuberculosis to 6-MP and ciprofloxacin resulted in significantly higher CFU
      than use of ciprofloxacin alone. These data may partially explain the paradoxical
      response of Crohn's disease patients infected with M. paratuberculosis to
      treatment with immunosuppressive thiopurine drugs, i.e., they do not worsen with
      anti-inflammatory treatment as would be expected with a microbiological etiologic
      pathogen. These findings also should influence the design of therapeutic trials
      to evaluate antibiotic treatments of Crohn's disease: AZA drugs may confound
      interpretation of data on therapeutic responses for both antibiotic-treated and
      control groups.

PMID- 18070972
TI  - Genetic and biochemical characterization of CAD-1, a chromosomally encoded new
      class A penicillinase from Carnobacterium divergens.
AB  - Carnobacterium divergens clinical isolates BM4489 and BM4490 were resistant to
      penicillins but remained susceptible to combinations of amoxicillin-clavulanic
      acid and piperacillin-tazobactam. Cloning and sequencing of the responsible
      determinant from BM4489 revealed a coding sequence of 912 bp encoding a class A
      beta-lactamase named CAD-1. The bla(CAD-1) gene was assigned to a chromosomal
      location in the two strains that had distinct pulsed-field gel electrophoresis
      patterns. CAD-1 shared 53% and 42% identity with beta-lactamases from Bacillus
      cereus and Staphylococcus aureus, respectively. Alignment of CAD-1 with other
      class A beta-lactamases indicated the presence of 25 out of the 26 isofunctional
      amino acids in class A beta-lactamases. Escherichia coli harboring bla(CAD-1)
      exhibited resistance to penams (benzylpenicillin and amoxicillin) and remained
      susceptible to amoxicillin in combination with clavulanic acid. Mature CAD-1
      consisted of a 34.4-kDa polypeptide. Kinetic analysis indicated that CAD-1
      exhibited a narrow substrate profile, hydrolyzing benzylpenicillin, ampicillin,
      and piperacillin with catalytic efficiencies of 6,600, 3,200, and 2,900 mM(-1) s(
      1), respectively. The enzyme did not interact with oxyiminocephalosporins,
      imipenem, or aztreonam. CAD-1 was inhibited by tazobactam (50% inhibitory
      concentration [IC(50)] = 0.27 microM), clavulanic acid (IC(50) = 4.7 microM), and
      sulbactam (IC(50) = 43.5 microM). The bla(CAD-1) gene is likely to have been
      acquired by BM4489 and BM4490 as part of a mobile genetic element, since it was
      not found in the susceptible type strain CIP 101029 and was adjacent to a gene
      for a resolvase.

PMID- 18070973
TI  - In vitro-selected linezolid-resistant Mycobacterium tuberculosis mutants.

PMID- 18070974
TI  - Deactivation of human immunodeficiency virus type 1 in medium by copper oxide
      containing filters.
AB  - Human immunodeficiency virus type 1 (HIV-1) can be transmitted through breast
      feeding and through contaminated blood donations. Copper has potent biocidal
      properties and has been found to inactivate HIV-1 infectivity. The objective of
      this study was to determine the capacity of copper-based filters to inactivate
      HIV-1 in culture media. Medium spiked with high titers of HIV-1 was exposed to
      copper oxide powder or copper oxide-impregnated fibers or passed through copper
      based filters, and the infectious viral titers before and after treatment were
      determined. Cell-free and cell-associated HIV-1 infectivity was inhibited when
      exposed to copper oxide in a dose-dependent manner, without cytotoxicity at the
      active antiviral copper concentrations. Similar dose-dependent inhibition
      occurred when HIV-1 was exposed to copper-impregnated fibers. Filtration of HIV-1
      through filters containing the copper powder or copper-impregnated fibers
      resulted in viral deactivation of all 12 wild-type or drug-resistant laboratory
      or clinical, macrophage-tropic and T-cell-tropic, clade A, B, or C, HIV-1
      isolates tested. Viral inactivation was not strain specific. Thus, a novel means
      to inactivate HIV-1 in medium has been developed. This inexpensive methodology
      may significantly reduce HIV-1 transmission from "mother to child" and/or through
      blood donations if proven to be effective in breast milk or plasma and safe for
      use. The successful application of this technology may impact HIV-1 transmission,
      especially in developing countries where HIV-1 is rampant.

PMID- 18070975
TI  - Are all the DNA gyrase mutations found in Mycobacterium leprae clinical strains
      involved in resistance to fluoroquinolones?
AB  - Mycobacterium leprae DNA gyrases carrying various mutations, previously described
      in clinical strains, were investigated for quinolone susceptibility by inhibition
      of supercoiling and DNA cleavage promotion. We demonstrated that the gyrA
      mutations leading to G89C or A91V confer fluoroquinolone resistance whereas the
      gyrB mutation leading to D205N does not.

PMID- 18070976
TI  - Biosynthetic investigations of lactonamycin and lactonamycin z: cloning of the
      biosynthetic gene clusters and discovery of an unusual starter unit.
AB  - The antibiotics lactonamycin and lactonamycin Z provide attractive leads for
      antibacterial drug development. Both antibiotics contain a novel aglycone core
      called lactonamycinone. To gain insight into lactonamycinone biosynthesis,
      cloning and precursor incorporation experiments were undertaken. The lactonamycin
      gene cluster was initially cloned from Streptomyces rishiriensis. Sequencing of
      ca. 61 kb of S. rishiriensis DNA revealed the presence of 57 open reading frames.
      These included genes coding for the biosynthesis of l-rhodinose, the sugar found
      in lactonamycin, and genes similar to those in the tetracenomycin biosynthetic
      gene cluster. Since lactonamycin production by S. rishiriensis could not be
      sustained, additional proof for the identity of the S. rishiriensis cluster was
      obtained by cloning the lactonamycin Z gene cluster from Streptomyces sanglieri.
      Partial sequencing of the S. sanglieri cluster revealed 15 genes that exhibited a
      very high degree of similarity to genes within the lactonamycin cluster, as well
      as an identical organization. Double-crossover disruption of one gene in the S.
      sanglieri cluster abolished lactonamycin Z production, and production was
      restored by complementation. These results confirm the identity of the genetic
      locus cloned from S. sanglieri and indicate that the highly similar locus in S.
      rishiriensis encodes lactonamycin biosynthetic genes. Precursor incorporation
      experiments with S. sanglieri revealed that lactonamycinone is biosynthesized in
      an unusual manner whereby glycine or a glycine derivative serves as a starter
      unit that is extended by nine acetate units. Analysis of the gene clusters and of
      the precursor incorporation data suggested a hypothetical scheme for
      lactonamycinone biosynthesis.

PMID- 18070977
TI  - Calcineurin inhibitor agents interact synergistically with antifungal agents in
      vitro against Cryptococcus neoformans isolates: correlation with outcome in solid
      organ transplant recipients with cryptococcosis.
AB  - Synergistic interactions were observed between CIs and antifungal agents against
      53 (90%) of 59 Cryptococcus neoformans isolates from solid organ transplant
      recipients with cryptococcosis and may account for better outcomes in patients
      with cryptococcosis receiving these immunosuppressive agents.

PMID- 18070978
TI  - Comparative in vitro activities of caspofungin and micafungin, determined using
      the method of the European Committee on Antimicrobial Susceptibility Testing,
      against yeast isolates obtained in France in 2005-2006.
AB  - The in vitro activities of caspofungin and micafungin against 1,038 yeast
      isolates have been determined. The caspofungin and micafungin MICs were lower for
      Candida albicans, Candida glabrata, and Candida tropicalis than for Candida
      parapsilosis, Candida guilliermondii, and Candida krusei. A clear correlation was
      seen between the MICs for the two drugs.

PMID- 18070980
TI  - Population pharmacokinetics of levofloxacin, gatifloxacin, and moxifloxacin in
      adults with pulmonary tuberculosis.
AB  - The objective of this study was to determine the population pharmacokinetic
      parameters of levofloxacin, gatifloxacin, and moxifloxacin following multiple
      oral doses. Twenty-nine patients with tuberculosis at the University Hospital in
      Vitoria, Brazil, participated. Subjects received multiple doses of one drug
      (levofloxacin, 1,000 mg daily, or gatifloxacin or moxifloxacin, 400 mg daily) as
      part of a 7-day study of early bactericidal activity. Serum samples were
      collected over 24 h after the fifth dose and assayed using validated high
      performance liquid chromatography assays. Concentration-time data were analyzed
      using noncompartmental, compartmental, and population methods. The three drugs
      were well tolerated. Levofloxacin produced the highest maximum plasma
      concentrations (median, 15.55 microg/ml; gatifloxacin, 4.75 microg/ml;
      moxifloxacin, 6.13 microg/ml), largest volume of distribution (median, 81 liters;
      gatifloxacin, 79 liters; moxifloxacin, 63 liters), and longest elimination half
      life (median, 7.4 h; gatifloxacin, 5.0 h; moxifloxacin, 6.5 h). A one-compartment
      model, with or without weight as a covariate, adequately described the data.
      Postmodeling simulations using median population parameter estimates closely
      approximated the median values from the original data. Area under the
      concentration-time curve/MIC ratios for free drug were high. All three quinolones
      showed favorable pharmacokinetic and pharmacodynamic indices, with the most
      favorable results in this population being seen with levofloxacin at the
      comparative doses used.

PMID- 18070979
TI  - In vivo pharmacodynamic characterization of anidulafungin in a neutropenic murine
      candidiasis model.
AB  - Multiple in vivo studies have characterized the pharmacodynamics of drugs from
      the triazole and polyene antifungal drug classes. Fewer studies have investigated
      these pharmacodynamic relationships for the echinocandin drug class. We used a
      neutropenic murine model of disseminated Candida albicans, Candida tropicalis,
      and Candida glabrata infection to characterize the time course of activity of the
      new echinocandin anidulafungin. The pharmacokinetic-pharmacodynamic (PK-PD)
      indices (the percentage of time that the drug concentration was above the MIC,
      the ratio of the area under the concentration-time curve from 0 to 24 h [AUC(0
      24)] to the MIC, and the ratio of the maximum serum drug concentration [C(max)]
      to the MIC) were correlated with in vivo efficacy, as measured by organism
      numbers in kidney cultures after 96 h of therapy. The kinetics following
      intraperitoneal anidulafungin dosing in neutropenic infected mice were monitored.
      Peak levels and AUCs were linear over the 16-fold dose range studied. The drug
      elimination half-life in serum ranged from 14 to 24 h. Single-dose postantifungal
      effect studies demonstrated prolonged suppression of organism regrowth after
      serum anidulafungin levels had fallen below the MIC. Of the four dosing intervals
      studied, treatment with the more widely spaced dosing regimens was most
      efficacious, suggesting the C(max)/MIC ratio as the PK-PD index most predictive
      of efficacy. Nonlinear regression analysis suggested that both the C(max)/MIC and
      AUC/MIC ratios were strongly predictive of treatment success. Studies were then
      conducted with 13 additional C. albicans, C. tropicalis, and C. glabrata isolates
      with various anidulafungin susceptibilities (MICs of anidulafungin for these
      strains, 0.015 to 2.0 microg/ml) to determine if similar C(max)/MIC and AUC(0
      24)/MIC ratios for these isolates were associated with efficacy. The
      anidulafungin exposures associated with efficacy were similar among Candida
      species.

PMID- 18070981
TI  - A case for immunization against nosocomial infections.
AB  - Immunization is a highly effective public health measure that reduces the
      incidence of infectious diseases, yet there has been relatively little effort
      toward the development of vaccines for nosocomial infections. Many nosocomial
      infections originate on mucosal surfaces (e.g., respiratory or gastrointestinal
      mucosa). As patients who are hospitalized once are more likely to be hospitalized
      again, we propose a prime-boost immunization strategy, whereby a priming dose of
      vaccine for a nosocomial infection is administered mucosally. Upon readmission, a
      parenteral boost would elicit a rapid immune response locally and systemically.
      Such a strategy could reduce or ameliorate nosocomial infections and perhaps
      limit dissemination of nosocomial pathogens. Thus, a more aggressive effort to
      develop vaccines for nosocomial infections is warranted.

PMID- 18070982
TI  - TRAF6 distinctively mediates MyD88- and IRAK-1-induced activation of NF-kappaB.
AB  - MyD88 and IL-1R-associated kinase 1 (IRAK-1) play crucial roles as adaptor
      molecules in signal transduction of the TLR/IL-1R superfamily, and it is known
      that expression of these proteins leads to the activation of NF-kappaB in a TNFR
      associated factor 6 (TRAF6)-dependent manner. We found in this study, however,
      that a dominant-negative mutant of TRAF6, lacking the N-terminal RING and zinc
      finger domain, did not inhibit IRAK-1-induced activation of NF-kappaB in human
      embryonic kidney 293 cells, although the TRAF6 mutant strongly suppressed the
      MyD88-induced activation. The dominant-negative mutant of TRAF6 did not affect
      the IRAK-1-induced activation, regardless of the expression level of IRAK-1. In
      contrast, small interfering RNA silencing of TRAF6 expression inhibited MyD88
      induced and IRAK-1-induced activation, and supplementation with the TRAF6
      dominant-negative mutant did not restore the IRAK-1-induced activation.
      Expression of IRAK-1, but not MyD88, induced the oligomerization of TRAF6, and
      IRAK-1 and the TRAF6 dominant-negative mutant were associated with TRAF6. These
      results indicate that TRAF6 is involved but with different mechanisms in MyD88
      induced and IRAK-induced activation of NF-kappaB and suggest that TRAF6 uses a
      distinctive mechanism to activate NF-kappaB depending on signals.

PMID- 18070983
TI  - NF-kappaB-dependent control of HIV-1 transcription by the second coding exon of
      Tat in T cells.
AB  - HIV-1 two-exon transactivator protein (Tat) is a 101-aa protein. We investigated
      the possible contribution of the extreme C terminus of HIV-1 Tat to maximize
      nuclear transcription factor NF-kappaB activation, long terminal repeat (LTR)
      transactivation, and viral replication in T cells. C-terminal deletion and
      substitution mutants made with the infectious clone HIV-89.6 were assayed for
      their ability to transactivate NF-kappaB-secreted alkaline phosphatase and HIV-1
      LTR-luciferase reporter constructs for low concentrations of Tat. A mutant
      infectious clone of HIV-89.6 engineered by introducing a stop codon at aa 72 in
      the Tat open-reading frame (HIVDeltatatexon2) replicated at a significantly lower
      rate than the wild-type HIV-89.6 in phytohemagglutinin-A/IL-2-stimulated primary
      peripheral blood lymphocytes. Altogether, our results suggest a critical role for
      the glutamic acids at positions 92, 94, and 96 or lysines at positions 88, 89,
      and 90, present in the second encoding Tat exon in activating NF-kappaB,
      transactivating the HIV-1 LTR and enhancing HIV-1 replication in T cells.

PMID- 18070985
TI  - Proteomics analysis of Hodgkin lymphoma: identification of new players involved
      in the cross-talk between HRS cells and infiltrating lymphocytes.
AB  - Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin lymphoma (HL) secrete factors
      that interact with inflammatory background cells and may serve as biomarkers for
      disease activity. To detect new proteins related to pathogenesis, we analyzed the
      secretome of HRS cells. Proteins in cell culture supernatant of 4 HL cell lines
      were identified using 1DGE followed by in-gel trypsin digestion and LC-MS/MS. In
      total, 1290 proteins, including 368 secreted proteins, were identified.
      Functional grouping of secreted proteins revealed 37 proteins involved in immune
      response. Sixteen of the 37 proteins (ie, ALCAM, Cathepsin C, Cathepsin S, CD100,
      CD150, CD26, CD44, CD63, CD71, Fractal-kine, IL1R2, IL25, IP-10, MIF, RANTES, and
      TARC) were validated in HL cell lines and patient material using
      immunohistochemistry and/or ELISA. Expression of all 16 proteins was confirmed in
      HL cell lines, and 15 were also confirmed in HL tissues. Seven proteins (ALCAM,
      cathepsin S, CD26, CD44, IL1R2, MIF, and TARC) revealed significantly elevated
      levels in patient plasma compared with healthy controls. Proteomics analyses of
      HL cell line supernatant allowed detection of new secreted proteins, which may
      add to our insights in the interaction between HRS cells and infiltrating
      lymphocytes and in some instances might serve as biomarkers.

PMID- 18070986
TI  - Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor
      growth by inducing PLCgamma1- and Ca2+-dependent apoptosis.
AB  - Herbs have successfully been used in traditional Chinese medicine for centuries.
      However, their curative mechanisms remain largely unknown. In this study, we show
      that Wogonin, derived from the traditional Chinese medicine Huang-Qin
      (Scutellaria baicalensis Georgi), induces apoptosis in malignant T cells in vitro
      and suppresses growth of human T-cell leukemia xenografts in vivo. Importantly,
      Wogonin shows almost no toxicity on T lymphocytes from healthy donors. Wogonin
      induces prolonged activation of PLCgamma1 via H(2)O(2) signaling in malignant T
      cells, which leads to sustained elevation of cytosolic Ca(2+) in malignant but
      not normal T cells. Subsequently, a Ca(2+) overload leads to disruption of the
      mitochondrial membrane. The selective effect of Wogonin is due to its
      differential regulation of the redox status of malignant versus normal T cells.
      In addition, we show that the L-type voltage-dependent Ca(2+) channels are
      involved in the intracellular Ca(2+) mobilization in T cells. Furthermore, we
      show that malignant T cells possess elevated amounts of voltage-dependent Ca(2+)
      channels compared with normal T cells, which further enhance the cytotoxicity of
      Wogonin for malignant T cells. Taken together, our data show a therapeutic
      potential of Wogonin for the treatment of hematologic malignancies.

PMID- 18070987
TI  - Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine kinase
      in human B-NHL rafts.
AB  - B-non-Hodgkin lymphomas (B-NHLs) use a raft-associated signalosome made of the
      constitutively active Lyn kinase, the tyrosine phosphorylated Cbp/PAG adaptor,
      and tyrosine phosphorylated STAT3 transcription factor. No such "signalosome" is
      found in rafts of ALK(+) T lymphoma and Hodgkin-derived cell lines, despite
      similar Cbp/PAG, Lyn, and STAT3 expression and similar amounts of raft
      sphingolipids. Stable association of the signalosome with B-NHL rafts requires
      (1) a Lyn kinase (auto)phosphorylated in its regulatory and active site
      tyrosines, (2) a Cbp/PAG adaptor phosphorylated at tyrosine 317 and bound to Lyn
      SH2 via phosphotyrosine 299 and neighboring residues, and (3) a tyrosine
      phosphorylated STAT3 linked via SH2 to the regulatory, C-terminal tyrosine of
      Lyn. No Csk appears to be part of this B-NHL signalosome. An oncogenic role for
      Lyn was shown after exposure of B-NHL lines to Lyn inhibitors that prevented Lyn
      and Cbp/PAG phosphorylation, dissociated the signalosome from rafts, and
      eventually induced death. Cell death followed decreases in Lyn or Cbp/PAG
      expression levels in one mantle cell lymphoma line, but not in a Hodgkin-derived
      one. The Lyn-Cbp/PAG signalosome appears to control proliferation and survival in
      most B-NHLs and constitutes a therapeutic target in B-NHL cells that exhibit
      oncogenic "addiction" to the Lyn kinase.

PMID- 18070988
TI  - Evidence of a relationship between infant birth weight and later diabetes and
      impaired glucose regulation in a Chinese population.
AB  - OBJECTIVE: The aim of this study was to determine the influence of birth weight,
      a marker of fetal growth, on the development of later impaired glucose metabolism
      throughout the life span of people living in China. RESEARCH DESIGN AND METHODS:
      We recorded detailed anthropometric data including height, weight, and health
      status and measured blood glucose levels and insulin concentrations after fasting
      and at 120 min of a standard oral glucose tolerance test from 2,019 eligible
      subjects born between 1921 and 1954 to investigate the risk of developing type 2
      diabetes and impaired glucose regulation (IGR). RESULTS: The diabetes and IGR
      groups were characterized by significantly lower birth weight (P < 0.001),
      smaller head circumference (P < 0.001), smaller ponderal index (P = 0.007), and
      shorter length (P = 0.004) compared with those in the normal glucose tolerance
      group. Using multiple logistic regression analysis, we observed that birth weight
      remained significantly associated with diabetes and IGR after adjustments for
      possible confounding variables at birth and in adult life such as sex, age,
      central obesity, smoking status, alcohol consumption, dyslipidemia, family
      history of diabetes, and occupational status (P = 0.027). There was a
      significantly increased risk of getting diabetes and IGR for those with low birth
      weight (odds ratio 1.748 [95% CI 1.018-3.001], P = 0.043). CONCLUSIONS: The
      results confirm that lower birth weight is an independent risk factor for later
      diabetes or IGR and show for the first time that this risk factor also applies
      for a Chinese population.

PMID- 18070989
TI  - Coffee consumption is associated with higher plasma adiponectin concentrations in
      women with or without type 2 diabetes: a prospective cohort study.
AB  - To test whether the beneficial effects of coffee consumption in metabolism might
      be explained by changes in circulating levels of adiponectin, we evaluated self
      reported habitual coffee and tea consumption and caffeine intake as predictors of
      plasma adiponectin concentrations among 982 diabetic and 1,058 nondiabetic women
      without cardiovascular disease from the Nurses' Health Study. Women with and
      without diabetes who drank >or=4 cups of coffee per day had significantly higher
      adiponectin concentrations than those who didn't drink coffee regularly (7.7 vs.
      6.1 microg/ml, respectively, in diabetic women, P = 0.004; 15.0 vs. 13.2
      microg/ml in nondiabetic women, P = 0.04). Similar associations were observed for
      caffeine intake. We confirm previously reported inverse associations of coffee
      consumption with inflammatory markers, C-reactive protein, and tumor necrosis
      factor-alpha receptor II. Adjustment for adiponectin did not weaken these
      associations, and adjustment for inflammatory markers did not attenuate the
      association between coffee consumption and adiponectin concentrations. High
      consumption of caffeine-containing coffee is associated with higher adiponectin
      and lower inflammatory marker concentrations.

PMID- 18070991
TI  - Objectively measured time spent sedentary is associated with insulin resistance
      independent of overall and central body fat in 9- to 10-year-old Portuguese
      children.
AB  - OBJECTIVE: We examined the independent relationships between objectively measured
      physical activity and insulin resistance in Portuguese children. RESEARCH DESIGN
      AND METHODS: This is a school-based, cross-sectional study in 147 randomly
      selected girls (aged 9.8 +/- 0.3 years; 27.8 +/- 9.3% body fat) and 161 boys
      (aged 9.8 +/- 0.3 years; 22.0 +/- 9.2% body fat). Physical activity was assessed
      by the Actigraph accelerometer for 4 days and summarized as time spent sedentary
      (accelerometer counts <500/min), in light-intensity (accelerometer counts 500
      2,000/min), and in moderate- and vigorous-intensity activity (accelerometer
      counts >2,001/min). We measured total and central fat mass by dual-energy X-ray
      absorptiometry. Insulin resistance was expressed as the homeostasis model
      assessment score. RESULTS: Time (min/day) spent sedentary was significantly and
      positively associated with insulin resistance (beta-coefficient = 0.001 [95% CI
      0.0002-0.002]; P = 0.013). Time spent in moderate- and vigorous-intensity
      physical activity (-0.002 [-0.003 to -0.001]; P = 0.0009) and overall physical
      activity (-0.001 [-0.008 to 0.003]; P < 0.0001) were significantly and inversely
      associated with insulin resistance. All associations remained statistically
      significant, although they were attenuated after further adjustments for sex,
      birth weight, sexual maturity, and total or central fat mass (P < 0.03).
      CONCLUSIONS: Physical activity is associated with insulin resistance independent
      of total and central fat mass in children. Our results emphasize the importance
      of decreasing sedentary behavior and increasing time spent in moderate- and
      vigorous-intensity activity in children, which may have beneficial effects on
      metabolic risk factors regardless of the degree of adiposity.

PMID- 18070990
TI  - Relationship of retinal vascular caliber with diabetes and retinopathy: the Multi
      Ethnic Study of Atherosclerosis (MESA).
AB  - OBJECTIVE: To examine the relationship of retinal vascular caliber with diabetes,
      glycemia, and diabetic retinopathy. RESEARCH DESIGN AND METHODS: Population-based
      study using data from the Multi-Ethnic Study of Atherosclerosis (MESA),
      comprising 5,976 individuals (whites, blacks, Hispanics, and Chinese) residing in
      six U.S. communities who were free of clinical cardiovascular disease at
      baseline. Retinal vascular caliber was measured from digital retinal photographs.
      RESULTS: There were 4,585 individuals with normal fasting glucose (NFG), 499 with
      impaired fasting glucose (IFG), 165 with diabetes with retinopathy signs, and 727
      with diabetes without retinopathy signs. After multivariate analysis, retinal
      arteriolar caliber increased from 143.8 microm in subjects with NFG to 144.5
      microm in IFG and 146.1 microm in diabetes (P < 0.001 for trend). Retinal venular
      caliber increased from 214.4 microm in NFG to 216.7 microm in IFG and 218.0
      microm in diabetes (P < 0.001 for trend). Retinal venular caliber was
      significantly larger with increasing levels of fasting glucose and A1C. In a
      subgroup analysis by ethnicity, the association between wider arteriolar caliber
      and diabetes was evident in whites only, whereas wider venular caliber and
      diabetes was evident in Hispanics and Chinese only. In people with diabetes, eyes
      with retinopathy had larger retinal venular but not arteriolar caliber.
      CONCLUSIONS: Retinal arteriolar and venular calibers are larger in individuals
      with diabetes, but the pattern of associations appears to vary by ethnicity.
      Retinal venular caliber is additionally associated with retinopathy signs. These
      findings add further to the concept that variations in retinal vascular caliber
      may reflect early diabetic microvascular damage.

PMID- 18070992
TI  - Multi-site testing with a point-of-care nerve conduction device can be used in an
      algorithm to diagnose diabetic sensorimotor polyneuropathy.
AB  - OBJECTIVE: We aimed to establish whether multi-nerve testing with a point-of-care
      nerve conduction device could be used to diagnose diabetic sensorimotor
      polyneuropathy. RESEARCH DESIGN AND METHODS: A total of 72 consecutive patients
      with diabetes underwent a full neurological examination and a concurrent
      evaluation for nine standard electrophysiological parameters using conventional
      nerve conduction studies (the reference standard) and a point-of-care device.
      RESULTS: Spearman coefficients for correlation of point-of-care and conventional
      parameters ranged between 0.76 and 0.91 (P < 0.001 in all comparisons). Agreement
      by the method of Bland and Altman was acceptable despite small systematic biases.
      Fifty subjects (69%) had neuropathy according to conventional criteria. The
      sensitivity and specificity for the point-of-care device to identify such
      neuropathy was 88 and 82%, respectively. CONCLUSIONS: A novel point-of-care
      device has reasonable diagnostic accuracy and thus may represent a sufficiently
      accurate alternative for detecting the diffuse electrophysiological criteria
      necessary to make the diagnosis of diabetic sensorimotor polyneuropathy.

PMID- 18070993
TI  - Diabetes Risk Calculator: a simple tool for detecting undiagnosed diabetes and
      pre-diabetes.
AB  - OBJECTIVE: The objective of this study was to develop a simple tool for the U.S.
      population to calculate the probability that an individual has either undiagnosed
      diabetes or pre-diabetes. RESEARCH DESIGN AND METHODS: We used data from the
      Third National Health and Nutrition Examination Survey (NHANES) and two methods
      (logistic regression and classification tree analysis) to build two models. We
      selected the classification tree model on the basis of its equivalent accuracy
      but greater ease of use. RESULTS: The resulting tool, called the Diabetes Risk
      Calculator, includes questions on age, waist circumference, gestational diabetes,
      height, race/ethnicity, hypertension, family history, and exercise. Each terminal
      node specifies an individual's probability of pre-diabetes or of undiagnosed
      diabetes. Terminal nodes can also be used categorically to designate an
      individual as having a high risk for 1) undiagnosed diabetes or pre-diabetes, 2)
      pre-diabetes, or 3) neither undiagnosed diabetes or pre-diabetes. With these
      classifications, the sensitivity, specificity, positive and negative predictive
      values, and receiver operating characteristic area for detecting undiagnosed
      diabetes are 88%, 75%, 14%, 99.3%, and 0.85, respectively. For pre-diabetes or
      undiagnosed diabetes, the results are 75%, 65%, 49%, 85%, and 0.75, respectively.
      We validated the tool using v-fold cross-validation and performed an independent
      validation against NHANES 1999-2004 data. CONCLUSIONS: The Diabetes Risk
      Calculator is the only currently available noninvasive screening tool designed
      and validated to detect both pre-diabetes and undiagnosed diabetes in the U.S.
      population.

PMID- 18070994
TI  - Influence of elevated cardiometabolic risk factor levels on treatment changes in
      type 2 diabetes.
AB  - Undertreatment of risk factors in patients with type 2 diabetes is common. We
      assessed the influence of elevated levels of blood pressure, total cholesterol,
      and A1C on decisions of Dutch general practitioners to change drug treatment in a
      cohort of 3,029 patients during a 1-year period. Respectively, 58, 71, and 21% of
      patients remained untreated despite poor blood pressure, lipid levels, and
      glycemic control. Of poorly controlled but already drug-treated patients, 52% did
      not receive intensification for antihypertensive medication, 81% not for lipid
      lowering medication, and 43% not for glucose-lowering medication. We observed a
      significantly lower treatment intervention rate in moderately than in poorly
      controlled patients for blood pressure. This was not seen for decisions on
      cholesterol or A1C results. The low overall action rates observed for blood
      pressure and especially lipid management cannot sufficiently be explained by the
      use of treatment thresholds higher than those indicated by guidelines.

PMID- 18070995
TI  - Effect of LDL cholesterol and treatment with losartan on end-stage renal disease
      in the RENAAL study.
AB  - Renal pathology and dyslipidemia commonly coexist. Treatments that lower
      albuminuria/proteinuria may lower lipids, but it is not known whether lipid
      lowering independent of lessening albuminuria/proteinuria slows progression of
      kidney disease. We examined the association between LDL cholesterol levels and
      treatment with losartan on end-stage renal disease (ESRD). Lipid levels and
      albuminuria measurements were obtained at baseline and at year 1 in a post hoc
      analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II
      Antagonist Losartan (RENAAL) study, which compared the effects of losartan-
      versus placebo-based antihypertensive therapy in patients with type 2 diabetes
      and nephropathy. LDL cholesterol lowering was associated with a lower risk of
      ESRD; however, this seemed to be largely an association with the reduction in
      albuminuria.

PMID- 18070996
TI  - Incidence and determinants of carpal tunnel decompression surgery in type 2
      diabetes: the Fremantle Diabetes Study.
AB  - To examine the incidence and predictors of carpal tunnel decompression (CTD) in
      community-based patients with type 2 diabetes, we studied 1,284 type 2 diabetic
      participants (mean +/- SD age 64.1 +/- 6.1 years, 49.1% male) in the longitudinal
      observational Fremantle Diabetes Study who had no history of CTD. A total of 67
      participants (5.8%) had a first CTD during 12,109 years (mean 9.4 +/- 3.7) of
      follow-up, an incidence of 5.5 per 1,000 patient-years. This was at least 4.2
      times the incidence in the general population (P < 0.001). In Cox proportional
      hazards analysis, significant independent determinants of first-ever CTD were
      higher BMI, taking lipid-lowering medication, and being in a stable relationship
      (P <or= 0.021). The crude incidence of first CTD is increased in type 2 diabetes
      and is associated with obesity and sociodemographic/treatment factors that could
      indicate treatment-seeking behavior including CTD in symptomatic patients.

PMID- 18070997
TI  - Stress burden and diabetes in two American Indian reservation communities.
AB  - OBJECTIVE: To examine the association between psychosocial stress and diabetes in
      two American Indian reservation communities (Northern Plains and Southwest).
      RESEARCH DESIGN AND METHODS: The American Indian Services Utilization,
      Psychiatric Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP), a
      cross-sectional probability sample survey, interviewed 3,084 randomly selected
      members of two American Indian tribal groups. Included were a psychiatric
      epidemiological interview, a physical health problems checklist, and an extensive
      sociodemographic section. RESULTS: Stress was common in these reservation
      communities, and the stress burden was greater among those with diabetes. After
      adjusting for sociodemographic characteristics, early-life interpersonal trauma
      and community family dysfunction were significantly associated with increased
      odds of diabetes in the Northern Plains, while discrimination and community
      addiction problems were significantly associated with increased odds of diabetes
      in the Southwest. CONCLUSIONS: A number of psychosocial stresses were
      significantly associated with increased odds of self-reported diabetes in these
      two American Indian communities.

PMID- 18070998
TI  - Insulin restriction and associated morbidity and mortality in women with type 1
      diabetes.
AB  - OBJECTIVE: To determine whether insulin restriction increases morbidity and
      mortality in women with type 1 diabetes. RESEARCH DESIGN AND METHODS: This is an
      11-year follow-up study of women with type 1 diabetes. A total of 234 women (60%
      of the original cohort) participated in the follow-up. Mean age was 45 years and
      mean diabetes duration was 28 years at follow-up. Mean BMI was 25 kg/m(2) and
      mean A1C was 7.9%. Measures of diabetes self-care behaviors, diabetes-specific
      distress, fear of hypoglycemia, psychological distress, and eating disorder
      symptoms were administered at baseline. At follow-up, mortality data were
      collected through state and national databases. Follow-up data regarding diabetes
      complications were gathered by self-report. RESULTS: Seventy-one women (30%)
      reported insulin restriction at baseline. Twenty-six women died during follow-up.
      Based on multivariate Cox regression analysis, insulin restriction conveyed a
      threefold increased risk of mortality after controlling for baseline age, BMI,
      and A1C. Mean age of death was younger for insulin restrictors (45 vs. 58 years,
      P < 0.01). Insulin restrictors reported higher rates of nephropathy and foot
      problems at follow-up. Deceased women had reported more frequent insulin
      restriction (P < 0.05) and reported more eating disorder symptoms (P < 0.05) at
      baseline than their living counterparts. CONCLUSIONS: Our data demonstrate that
      insulin restriction is associated with increased rates of diabetes complications
      and increased mortality risk. Mortality associated with insulin restriction
      appeared to occur in the context of eating disorder symptoms, rather than other
      psychological distress. We propose a screening question appropriate for routine
      diabetes care to improve detection of this problem.

PMID- 18070999
TI  - A prospective study of cardiorespiratory fitness and risk of type 2 diabetes in
      women.
AB  - OBJECTIVE: The purpose of this study was to determine the independent and joint
      associations of cardiorespiratory fitness (CRF) and BMI with the incidence of
      type 2 diabetes in women. RESEARCH DESIGN AND METHODS: An observational cohort of
      6,249 women aged 20-79 years was free of baseline cardiovascular disease, cancer,
      and diabetes. CRF was measured using a maximal treadmill exercise test. BMI was
      computed from measured height and weight. The incidence of type 2 diabetes was
      identified primarily by 1997 American Diabetes Association criteria. RESULTS:
      During a 17-year follow-up, 143 cases of type 2 diabetes occurred. Compared with
      the least fit third, the multivariate (including BMI)-adjusted hazard ratio (HR)
      (95% CI) was 0.86 (0.59-1.25) for the middle third and 0.61 (0.38-0.96) for the
      upper third of CRF. For BMI, the multivariate (including CRF)-adjusted HR (95%
      CI) was 2.34 (1.55-3.54) for overweight individuals and 3.70 (2.12-6.44) for
      obese individuals, compared with normal-weight patients. In the combined
      analyses, overweight/obese unfit (the lowest one-third of CRF) women had
      significantly higher risks compared with normal-weight fit (the upper two-thirds
      of CRF) women. CONCLUSIONS: Low CRF and higher BMI were independently associated
      with incident type 2 diabetes. The protective effect of CRF was observed in
      individuals who were overweight or obese, but CRF did not eliminate the increased
      risk in these groups. These findings underscore the critical importance of
      promoting regular physical activity and maintaining normal weight for diabetes
      prevention.

PMID- 18071000
TI  - Plasma glucose regulation and mortality in pima Indians.
AB  - OBJECTIVE: To evaluate whether impaired fasting glucose (IFG) and/or impaired
      glucose tolerance (IGT) are associated with increased risk of mortality and
      prevalent ischemic heart disease (IHD) and to analyze if the increased risk of
      death is dependent on subsequent development of diabetes in Pima Indians.
      RESEARCH DESIGN AND METHODS: A total of 2,993 Pima Indians aged >or=35 years were
      included. Prevalent IHD, defined by major ischemic electrocardiogram changes, was
      evaluated according to the following glucose/diabetes categories: normal glucose
      regulation (NGR), IFG and/or IGT, and diabetic groups by duration. During a
      median follow-up of 10.4 years, 780 subjects died from natural causes and 156 of
      these died from IHD. Mortality was analyzed according to the same
      glucose/diabetes categories at baseline and then as time-dependent variables.
      RESULTS: Only subjects with diabetes >or=15 years of duration have a higher
      prevalence of IHD (odds ratio 1.9 [95% CI 1.4-2.5]) relative to NGR. In baseline
      and time-dependent models, age- and sex-adjusted death rates from natural causes
      and from IHD were similar among the nondiabetic groups. Among diabetic subjects,
      natural mortality was higher in those with >or=15 years diabetes duration (death
      rate ratio [DRR] relative to NGR = 2.6 [95% CI 2.1-3.3]). IHD mortality was
      higher in subjects with long diabetes duration (DRR for diabetes 10-15 years =
      3.8 [1.5-9.5]; DRR for diabetes >or=15 years = 8.6 [3.8-19.4]) in the time
      dependent model. CONCLUSIONS: Natural and IHD mortality are not increased in Pima
      Indians with IFG and/or IGT. Only after the onset of diabetes do the rates of
      these events increase relative to NGR.

PMID- 18071001
TI  - Metabolic and immunological features of the failing islet-transplanted patient.
AB  - OBJECTIVE: This retrospective study was designed to identify metabolic and immune
      predictors of early islet allograft failure. RESEARCH DESIGN AND METHODS: We
      measured several metabolic and immunological markers at the time of pretransplant
      and several time points posttransplantation in 17 patients with long-term
      functioning graft (long fx) and 20 patients with short-term functioning graft
      (short fx). RESULTS: The short fx group showed higher insulin resistance, altered
      proinsulin processing, lower soluble interleukin-2 receptor (sIL-2r) (marker of T
      cell activation), and higher soluble FasL (marker of apoptosis) during the entire
      follow-up, particularly at time of failure. CONCLUSIONS: Patients who experienced
      an early failure of islet allograft showed specific metabolic and immunological
      signs long before islet failure.

PMID- 18071003
TI  - Underweight as a predictor of diabetes in older adults: a large cohort study.

PMID- 18071002
TI  - Elevated depression symptoms, antidepressant medicine use, and risk of developing
      diabetes during the diabetes prevention program.
AB  - OBJECTIVE: To assess the association between elevated depression symptoms or
      antidepressant medicine use on entry to the Diabetes Prevention Program (DPP) and
      during the study and the risk of developing diabetes during the study. RESEARCH
      DESIGN AND METHODS: DPP participants (n = 3,187) in three treatment arms
      (intensive lifestyle [ILS], metformin [MET], and placebo [PLB]) completed the
      Beck Depression Inventory (BDI) and reported their use of antidepressant
      medication at randomization and throughout the study (average duration in study
      3.2 years). RESULTS: When other factors associated with the risk of developing
      diabetes were controlled, elevated BDI scores at baseline or during the study
      were not associated with diabetes risk in any arm. Baseline antidepressant use
      was associated with diabetes risk in the PLB (hazard ratio 2.25 [95% CI 1.38
      3.66]) and ILS (3.48 [1.93-6.28]) arms. Continuous antidepressant use during the
      study (compared with no use) was also associated with diabetes risk in the same
      arms (PLB 2.60 [1.37-4.94]; ILS 3.39 [1.61-7.13]), as was intermittent
      antidepressant use during the study in the ILS arm (2.07 [1.18-3.62]). Among MET
      arm participants, antidepressant use was not associated with developing diabetes.
      CONCLUSIONS: A strong and statistically significant association between
      antidepressant use and diabetes risk in the PLB and ILS arms was not accounted
      for by measured confounders or mediators. If future research finds that
      antidepressant use independently predicts diabetes risk, efforts to minimize the
      negative effects of antidepressant agents on glycemic control should be pursued.

PMID- 18071004
TI  - Breast-feeding and type 2 diabetes in the youth of three ethnic groups: the
      SEARCh for diabetes in youth case-control study.
AB  - OBJECTIVE: To evaluate the hypothesis that breast-feeding is associated with
      reduced type 2 diabetes among African-American, Hispanic, and non-Hispanic white
      youth, mediated in part by current weight status. RESEARCH DESIGN AND METHODS:
      The SEARCH Case-Control Study, an ancillary study to SEARCH for Diabetes in
      Youth, was conducted in two of six SEARCH clinical sites. Eighty youth with type
      2 diabetes aged 10-21 years were included. Nondiabetic control participants were
      recruited from primary care provider offices (n = 167). Breast-feeding
      information was recalled by biological mothers. RESULTS: Prevalence (%) of breast
      feeding (any duration) was lower among youth with type 2 diabetes than among
      control subjects (19.5 vs. 27.1 for African Americans, 50.0 vs. 83.8 for
      Hispanics, and 39.1 vs. 77.6 for non-Hispanic whites). The overall crude odds
      ratio for the association of breast-feeding (ever versus never) and type 2
      diabetes was 0.26 (95% CI 0.15-0.46). Results were similar by race/ethnic group
      (P value for interaction = 0.17). The odds ratio for the association after
      adjusting for 12 potential confounders was 0.43 (0.19-0.99). When current BMI z
      score was added to the model, the odds ratio was attenuated (0.82 [0.30-2.30]),
      suggesting possible mediation through current childhood weight status. Analyses
      that incorporated duration of breast-feeding, adjusted for potential confounders,
      provided evidence for dose response (test for trend, P value <0.0001), even after
      inclusion of BMI z-score. CONCLUSIONS: Breast-feeding appears to be protective
      against development of type 2 diabetes in youth, mediated in part by current
      weight status in childhood.

PMID- 18071005
TI  - Diabetes- and nondiabetes-related lower extremity amputation incidence before and
      after the introduction of better organized diabetes foot care: continuous
      longitudinal monitoring using a standard method.
AB  - OBJECTIVE: There is a lack of continuous longitudinal population-based data on
      lower extremity amputation (LEA) in the U.K. We present here accurate data on
      trends in diabetes-related (DR) LEAs and non-DRLEAs in the South Tees area over a
      continuous 5-year period. RESEARCH DESIGN AND METHODS: All cases of LEA from 1
      July 1995 to 30 June 2000 within the area were identified. Estimated
      ascertainment using capture-recapture analysis approached 100% for LEAs in the
      area. Data were collected longitudinally using the standard method of the Global
      Lower Extremity Amputation Study protocol. RESULTS: Over 5 years there were 454
      LEAs (66.3% men) in the South Tees area, of which 223 were diabetes related
      (49.1%). Among individuals with diabetes, LEA rates went from 564.3 in the first
      year to 176.0 of 100,000 persons with diabetes in the fifth year. Over the same
      period, non-DRLEAs increased from 12.3 to 22.8 of 100,000 persons without
      diabetes. The relative risk of a person with diabetes undergoing an LEA went from
      being 46 times that of a person without diabetes to 7.7 at the end of the 5
      years. The biggest improvement in LEA incidence was seen in the reduction of
      repeat major DRLEAs. CONCLUSIONS: Our data show that in the South Tees area at a
      time when major non-DRLEA rates increased, major DRLEA rates have fallen. These
      diverging trends mark a significant improvement in care for patients with
      diabetic foot disease as a result of better organized diabetes care.

PMID- 18071006
TI  - Associations between diabetes and clinical markers of benign prostatic
      hyperplasia among community-dwelling Black and White men.
AB  - OBJECTIVE: The aim of this study was to examine associations between diabetes and
      clinical markers of benign prostatic hyperplasia (BPH) in community-dwelling
      white and black men aged 40-79 years. RESEARCH DESIGN AND METHODS: Data from the
      Olmsted County Study of Urinary Symptoms and Health Status and the Flint Men's
      Health Study were combined for a total study sample of 2,484 men. Severity of
      lower urinary tract symptoms (LUTS), peak urinary flow rates, prostate volume,
      and serum prostate-specific antigen (PSA) levels were examined by self-reported
      physician-diagnosed diabetes. RESULTS: Overall, 170 men (6.8%) reported a history
      of diabetes. Increased irritative LUTS and specifically nocturia were positively
      associated with diabetes. These patterns were consistent across race and
      persisted after adjustment for age, BMI, and various indicators of socioeconomic
      status. Furthermore, the relationship between irritative LUTS and diabetes was
      greater in black men. No significant associations were observed between diabetes
      and prostate volume, PSA level, and peak urinary flow rate. CONCLUSIONS: Our
      multiethnic community-based study demonstrates positive associations between
      diabetes and irritative LUTS and nocturia. Moreover, the association between
      irritative LUTS and diabetes is increased in black men. There was no strong
      evidence for an association between diabetes and BPH across measures more
      specific to BPH (i.e., prostate volume, PSA, and peak urinary flow rate). Taken
      together, our findings suggest that the presence of diabetes may be less related
      to prostate growth and more related to the dynamic components of lower urinary
      tract function. Further evaluations of the association between diabetes and BPH
      and related racial variations are warranted.

PMID- 18071007
TI  - Prevalence of the metabolic syndrome among U.S. adolescents using the definition
      from the International Diabetes Federation.
AB  - OBJECTIVE: Our objective was to estimate the prevalence of the metabolic syndrome
      using the 2007 pediatric International Diabetes Federation (IDF) definition among
      adolescents in the U.S. RESEARCH DESIGN AND METHODS: We used data from 2,014
      participants aged 12-17 years of the National Health and Nutrition Examination
      Survey 1999-2004. RESULTS: The prevalence of the metabolic syndrome for the
      period 1999-2004 was approximately 4.5% ( approximately 1.1 million adolescents
      aged 12-17 years in 2006). It increased with age, was higher among males (6.7%)
      than females (2.1%) (P = 0.006), and was highest among Mexican-American
      adolescents (7.1%). The prevalence of the metabolic syndrome was relatively
      stable across the 6-year period: 4.5% for 1999-2000, 4.4-4.5% for 2001-2002, and
      3.7-3.9% for 2003-2004 (P for linear trend >0.050). CONCLUSIONS: Our results
      provide the first estimates of the prevalence of the metabolic syndrome using the
      pediatric IDF definition among adolescents in the U.S.

PMID- 18071008
TI  - Optimal cut points of waist circumference for the clinical diagnosis of metabolic
      syndrome in the Japanese population.

PMID- 18071009
TI  - Effect of a gonadotrophin-releasing hormone analogue on lung function in
      lymphangioleiomyomatosis.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM), a multisystem disease occurring
      primarily in women, is characterized by cystic lung destruction, and kidney and
      lymphatic tumors, caused by the proliferation of abnormal-appearing cells (ie,
      LAM cells) with a smooth muscle cell phenotype that express melanoma antigens and
      are capable of metastasizing. Estrogen receptors are present in LAM cells, and
      this finding, along with reports of disease progression during pregnancy or
      following exogenous estrogen administration, suggest the involvement of estrogens
      in the pathogenesis of LAM. Consequently, antiestrogen therapies have been
      employed in treatment. The goal of this prospective study was to evaluate the
      efficacy of triptorelin, a gonadotrophin-releasing hormone analogue, in 11
      premenopausal women with LAM. METHODS: Patients were evaluated at baseline and
      every 3 to 6 months thereafter, for a total of 36 months. Hormonal assays,
      pulmonary function tests, 6-min walk tests, high-resolution CT scans of the
      chest, and bone mineral density studies were performed. RESULTS: Gonadal
      suppression was achieved in all patients. Overall, a significant decline in lung
      function was observed; two patients underwent lung transplantation 1 year after
      study enrollment, and another patient was lost to follow-up. Treatment with
      triptorelin was associated with a decline in bone mineral density. CONCLUSIONS:
      Triptorelin appears not to prevent a decline in lung function in patients with
      LAM. Its use, however, may be associated with the loss of bone mineral density.

PMID- 18071010
TI  - Is metalloproteinase-7 specific for idiopathic pulmonary fibrosis?
AB  - BACKGROUND: Matrix metalloproteinase (MMP)-7 was reported to be a key molecule in
      the pathogenesis of idiopathic pulmonary fibrosis (IPF) based on the result of
      microarray analysis and knockout mice. However, the role of MMP-7 has not been
      determined in other types of idiopathic interstitial pneumonia (IIP). The aim of
      this study was to investigate the role of MMP-7 in IIP by comparing its
      expression in usual interstitial pneumonia (UIP) and cryptogenic organizing
      pneumonia (COP). METHODS: Levels of MMP and tissue inhibitors of
      metalloproteinase in BAL fluid and their expression on lung tissues were compared
      between normal control subjects (n = 5) and the patients with IPF (n = 6) and COP
      (n = 11). RESULTS: There was no significant difference in BAL fluid MMP-7 levels
      between UIP and COP, although it was higher in both diseases compared to normal
      control subjects. Furthermore, the pattern and the degree of MMP-7 expression in
      lung tissues were also similar in both IPF and COP, whereas MMP-2 level was
      higher in COP and MMP-9 level was higher in IPF. CONCLUSION: MMP-7 seems to play
      an important role in the pathogenesis of not only IPF but also COP; therefore, it
      may not be the key factor determining the prognosis or reversibility of IIPs.

PMID- 18071011
TI  - Sputum eosinophils and the response of exercise-induced bronchoconstriction to
      corticosteroid in asthma.
AB  - BACKGROUND: The relationship between eosinophilic airway inflammation and
      exercise-induced bronchoconstriction (EIB), and the response to inhaled
      corticosteroid (ICS) therapy was examined. METHODS: Twenty-six steroid-naive
      asthmatic patients with EIB were randomized to two parallel, double-blind,
      crossover study arms (13 subjects in each arm). Each arm compared two dose levels
      of inhaled ciclesonide that were administered for 3 weeks with a washout period
      of 3 to 8 weeks, as follows: (1) 40 vs 160 microg daily; and (2) 80 vs 320 microg
      daily. Baseline and weekly assessments with exercise challenge and sputum
      analysis were performed. RESULTS: Data were pooled and demonstrated that 10
      subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy
      (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil
      percentage. Sputum eosinophil percentage significantly correlated with EIB
      severity, and predicted the magnitude and temporal response of EIB to high-dose
      therapy, but not to low-dose therapy (ie, 40 and 80 microg). Low-dose ICS therapy
      provided a significant reduction in EIB at 1 week, with little additional
      improvement thereafter, irrespective of baseline sputum eosinophil counts. In
      contrast, high-dose ICS therapy provided a significantly greater improvement in
      EIB in subjects with sputum eosinophilia compared to those with an eosinophil
      count of < 5%. The difference between the eosinophilic groups in the magnitude of
      improvement in EIB was evident after the first week of high-dose ICS therapy and
      increased with time. CONCLUSIONS: These results suggest that eosinophilic airway
      inflammation may be important in modifying the severity of EIB and the response
      to ICS therapy. Measurements of sputum eosinophil percentage may, therefore, be
      useful in predicting the magnitude and temporal response of EIB to different dose
      levels of ICSs. TRIAL REGISTRATION: clinicaltrial.gov; Identifier: NCT00525772.

PMID- 18071012
TI  - Marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: imaging
      findings in 21 patients.
AB  - BACKGROUND: Few articles have been published on imaging findings of marginal zone
      B-cell lymphoma of bronchus-associated lymphoid tissue (BALT) of the lung. We
      present CT scan and 18F-fluorodeoxyglucose (FDG) PET scan findings of the
      disease. METHODS: From March 1995 to February 2007, 21 pretreatment patients
      (male patients, 9; female patients, 12; age range, 35 to 76 years; mean [+/- SD]
      age, 54 +/- 10.4 years) were seen who had pathologic diagnoses of marginal zone B
      cell lymphoma of BALT. After CT scans were reviewed searching for specific
      patterns and distribution of parenchymal lung lesions, patients were classified
      as having the following four different patterns: (1) single nodular or
      consolidative; (2) multiple nodular or areas of consolidation; (3) bronchiectasis
      and bronchiolitis; and (4) diffuse interstitial lung disease (DILD) patterns. In
      six patients, in whom PET/CT scanning was performed, the pattern and the extent
      of maximum standardized uptake values (mSUVs) of FDG uptake were described.
      RESULTS: A single nodular or consolidative pattern was observed in 7 of 21 (33%)
      patients, multiple nodular or areas of consolidation were observed in 9 patients
      (43%), bronchiectasis and bronchiolitis were observed in 3 patients (14%), and
      DILD was observed in 2 patients (10%). On PET scans (n = 6), lesions showed
      heterogeneous FDG uptake in five patients and homogeneous uptake in one patient,
      with mSUVs ranging from 2.2 to 6.3 (mean mSUV, 4.2 +/- 1.48). CONCLUSIONS:
      Marginal zone B-cell lymphomas of BALT manifest diverse patterns of lung
      abnormality on CT scans, but single or multiple nodules or areas of consolidation
      are the main patterns that occur in a majority (76%) of patients. Most lesions
      show heterogeneous but identifiable FDG uptake on PET scans.

PMID- 18071013
TI  - Exercise oscillatory ventilation: instability of breathing control associated
      with advanced heart failure.
AB  - BACKGROUND: Instability of breathing control due to heart failure (HF) manifests
      as exercise oscillatory ventilation (EOV). Prior descriptions of patients with
      EOV have not been controlled and have been limited to subjects with left
      ventricular ejection fraction (LVEF) of <or= 0.40. The aim of this study was to
      compare clinical characteristics including ventilatory responses of subjects with
      EOV to those of control subjects with HF matched for LVEF. METHODS: Subjects (n =
      47) were retrospectively identified from 1,340 consecutive patients referred for
      cardiopulmonary exercise testing. Study inclusion required EOV without
      consideration of LVEF while control subjects (n = 47) were composed of HF
      patients with no EOV matched for LVEF. Characteristics for each group were
      summarized and compared. RESULTS: For EOV subjects, the mean LVEF was 0.37
      (range, 0.11 to 0.70), and 19 subjects (41%) had an LVEF of >or= 0.40. Compared
      to control subjects, EOV subjects had increased left atrial dimension, mitral E
      wave velocity, and right heart pressures as well as decreased exercise tidal
      volume response, functional capacity, rest and exercise end-tidal carbon dioxide,
      and increased ventilatory equivalent for carbon dioxide and dead space
      ventilation (all p < 0.05). Multivariate analysis demonstrated atrial
      fibrillation (odds ratio, 6.7; p = 0.006), digitalis therapy (odds ratio, 0.27; p
      = 0.02), New York Heart Association class (odds ratio, 3.5; p = 0.0006), rest end
      tidal carbon dioxide (odds ratio, 0.87; p = 0.005), and peak heart rate (odds
      ratio, 0.98; p = 0.02) were independently associated with EOV. CONCLUSIONS:
      Patients with EOV have clinical characteristics and exercise ventilatory
      responses consistent with more advanced HF than patients with comparable LV
      systolic function; EOV may occur in HF patients with an LVEF of >or= 0.40.

PMID- 18071014
TI  - Factors associated with failure to complete isoniazid treatment for latent
      tuberculosis infection in Rhode Island.
AB  - BACKGROUND: The treatment of latent tuberculosis infection (LTBI) is essential
      for tuberculosis elimination in the United States, but the major limitation is
      poor adherence to therapy. To aid the design of targeted adherence interventions,
      we investigated the factors associated with noncompletion of isoniazid (INH)
      therapy for LTBI. METHODS: A retrospective analysis of patients with who failed
      to complete vs those who completed 9 months of INH therapy at the RISE TB Clinic
      (Miriam Hospital; Providence, RI) in 2003 was performed. Factors associated with
      treatment noncompletion were examined using univariate and multiple logistic
      regression analysis. RESULTS: Of 845 patients with LTBI, 690 patients (81.6%)
      initiated INH therapy, of whom 426 patients (61.7%) completed therapy, and 246
      patients (35.6%) were lost to follow-up. Treatment was discontinued in 18
      patients (2.6%). Patients who failed to complete therapy were younger (mean age,
      30.6 vs 33.8 years, respectively; p = 0.006), and were more likely to be
      uninsured (42.9% vs 29.8%, respectively; p = 0.0004), to be postpartum (66.7% vs
      37.3%, respectively; p = 0.043), and to report treatment side effects (54.8% vs
      30.1%, respectively; p < 0.0001). Reported treatment side effects (odds ratio
      [OR], 3.6; 95% confidence interval [CI], 2.2 to 6.2) and lack of medical
      insurance (OR, 1.7; 95% CI, 1.1 to 2.7) were each associated with treatment
      noncompletion in a model including both. Also, pregnant women were more likely
      than nonpregnant women to fail to initiate INH treatment (52.1% vs 14.7%,
      respectively; p < 0.0001). CONCLUSIONS: LTBI patients who are young, pregnant or
      postpartum, uninsured, and/or report treatment side effects may require
      additional case management to improve INH treatment completion rates.

PMID- 18071015
TI  - Prognostic significance of thin-section CT scan findings in small-sized lung
      adenocarcinoma.
AB  - OBJECTIVES: The purpose of this study is to evaluate the prognostic importance of
      thin-section (TS) CT scan findings in small-sized lung adenocarcinomas. PATIENTS
      AND METHODS: We reviewed TS-CT scan findings and pathologic specimens from 359
      consecutive patients who underwent surgical resection for peripheral lung
      adenocarcinomas <or= 20 mm in diameter during the period from July 1997 to May
      2006. By using TS-CT scan images, tumors were defined as air-containing types if
      the maximum diameter of tumor opacity on mediastinal window images was less than
      or equal to half of that seen on lung window images, and as a solid-density type
      if the maximum diameter on the mediastinal window images was more than half of
      that on lung window images. We compared TS-CT scan findings to pathologic
      findings (ie, lymph node metastasis, pleural invasion, vessel invasion, and
      lymphatic invasion) and prognosis. The following prognostic factors were analyzed
      by chi2 test and Cox proportional hazard model: age; gender; tumor size;
      pathologic stage; TS-CT scan findings; histologic subtypes defined by Noguchi et
      al (ie, Noguchi type); pleural involvement; lymphatic invasion; and vascular
      invasion. RESULTS: No pathologic invasive findings or recurrence were found in
      patients with air-containing-type tumors. Pathologic invasive findings and
      recurrence were found in 10 to 30% of patients with solid-density-type tumors.
      The air-containing type tumors seen on TS-CT scans and Noguchi type A or B tumors
      were demonstrated as prognostic factors for good outcome by chi2 test (p <
      0.001). Multivariate analyses revealed lymphatic permeation as a significant
      prognostic factor. CONCLUSION: The TS-CT scan findings were important predictive
      factors for postsurgical outcome in patients with lung adenocarcinoma.

PMID- 18071016
TI  - Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: The prognostic value of BAL fluid cell count differential in patients
      with idiopathic pulmonary fibrosis (IPF) is unknown. We hypothesized that
      baseline BAL fluid cell count differential (ie, elevated levels of neutrophils
      and eosinophils, or reduced levels of lymphocytes) would predict higher mortality
      among persons with IPF. METHODS: We evaluated the association of BAL fluid cell
      count differential and mortality among 156 persons with surgical lung biopsy
      proven IPF who underwent bronchoscopy with BAL and cell count differential
      measurements at presentation. Vital status was obtained among all participants.
      Cox regression analysis evaluated the association of BAL fluid cell count
      differential and mortality. RESULTS: After controlling for known clinical
      predictors of mortality, we found that each doubling of baseline BAL fluid
      neutrophil percentage was associated with a 30% increased risk of mortality
      (adjusted hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.01 to 1.62;
      adjusted p = 0.04) in the first year after presentation. We observed no
      association with BAL fluid lymphocyte percentage and mortality (adjusted HR per
      doubling, 0.99; 95% CI, 0.76 to 1.29; p = 0.93) or eosinophil percentage and
      mortality (adjusted HR per doubling, 0.99; 95% CI, 0.69 to 1.40; p = 0.95).
      CONCLUSIONS: Increased BAL fluid neutrophil percentage is an independent
      predictor of early mortality among persons with IPF. Alternatively, BAL fluid
      lymphocyte and eosinophil percentages were not associated with mortality. The
      clinical utility of BAL at the time of diagnosis of IPF should be reconsidered.

PMID- 18071018
TI  - Facial and ocular deposition of nebulized budesonide: effects of face mask
      design.
AB  - BACKGROUND: In vivo case reports and in vitro studies have indicated that aerosol
      therapy using face masks can result in drug deposition on the face and in the
      eyes, and that face mask design may affect drug delivery. OBJECTIVE: To test
      different mask/nebulizer combinations for budesonide, a nebulized steroid used to
      treat pediatric patients with asthma. METHODS: Using high-performance liquid
      chromatography, drug delivery (inhaled mass), facial, and ocular deposition of
      budesonide aerosols were studied in vitro using a ventilated face facsimile
      (tidal volume, 50 mL; rate, 25 breaths/min, duty cycle 0.4), a tight-fitting test
      mask, a standard commercial mask, and a prototype mask designed to optimize
      delivery by reducing particle inertia. Nebulizer insertion into the mask (front
      loaded vs bottom loaded) was also tested. Particle size was measured by cascade
      impaction. Pari LC Plus (PARI Respiratory Equipment; Midlothian, VA) and MistyNeb
      (Allegiance; McGaw Park, IL) nebulizers were tested. RESULTS: Inhaled mass for
      tight-fitting and prototype masks was similar (13.2 +/- 1.85% vs 14.4 +/- 0.67%
      [percentage of nebulizer charge], p = 0.58) and significantly greater than for
      the commercial mask (3.03 +/- 0.26%, p = 0.005). Mask insertion of nebulizer was
      a key factor (inhaled mass: front loaded vs bottom loaded, 8.23 +/- 0.18% vs 3.03
      +/- 0.26%; p = 0.005). Ocular deposition varied by an order of magnitude and was
      a strong function of mask design (4.77 +/- 0.24% vs 0.35 +/- 0.05%, p = 0.002,
      tight fitting vs prototype). Particle sizes (7.3 to 9 microm) were larger than
      previously reported for budesonide. CONCLUSIONS: For pediatric breathing
      patterns, mask design is a key factor defining budesonide delivery to the lungs,
      face, and eyes. Front-loaded nebulizer mask combinations are more efficient than
      bottom-loaded systems.

PMID- 18071017
TI  - Differences in airway cytokine profile in severe asthma compared to moderate
      asthma.
AB  - BACKGROUND: Some studies of severe asthma suggest that persistence or alteration
      in the pattern of inflammation may be associated with the severity of the
      disease. Whether there are differences in the expression of the principal
      cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation
      in the airway tissues of severe compared to moderate asthmatics has not been
      determined. The aim of this study was to compare the patterns of expression of
      representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines
      (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated
      chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and
      moderate asthma. METHODS: Subjects with severe asthma (n = 24) and a comparison
      moderate asthma group (n = 26) were assessed using spirometry, induced sputum,
      exhaled nitric oxide, and bronchial biopsy. The expression of proteins of
      interest in the epithelium and subepithelium of the airway wall was examined by
      immunocytochemistry. RESULTS: Subjects with severe asthma were more symptomatic,
      had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia
      (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma
      expression were increased and IL-4 expression was decreased in severe asthma
      compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5
      expression did not differ between the groups. CONCLUSION: Patients with severe
      asthma have increases in neutrophils and eosinophils in the sputum, and differ in
      airway cytokine/chemokine expression from moderate asthmatics. Excess
      neutrophilia may be explained by increased expression of IL-8, but differences in
      eosinophilia do not appear to be associated with IL-5 and eotaxin expression.

PMID- 18071019
TI  - Right and left ventricular function and pulmonary artery pressure in patients
      with bronchiectasis.
AB  - BACKGROUND: Bronchiectasis may have deleterious effects on cardiac function
      secondary to pulmonary hypertension (PH). This study was designed to assess
      cardiac function and determine the prevalence of PH in patients with cystic and
      cylindrical bronchiectasis. METHODS: A cross-sectional study of patients with
      bronchiectasis diagnosed by CT scan was conducted at King Khalid University
      Hospital, Riyadh, Saudi Arabia between December 2005 and January 2007. Pulmonary
      function tests were performed, arterial blood gas measurements were made, and
      cardiac function and systolic pulmonary artery pressure (SPAP) were assessed by
      echocardiography. RESULTS: Of 94 patients (31% men, n = 29), 62 patients (66%)
      had cystic bronchiectasis and 32 patients (34%) had cylindrical bronchiectasis.
      Right ventricular (RV) systolic dysfunction was observed in 12 patients (12.8%),
      left ventricular (LV) systolic dysfunction was observed in 3 patients (3.3%), and
      LV diastolic dysfunction was observed in 11 patients (11.7%); all had cystic
      bronchiectasis. RV dimensions were significantly greater in the cystic
      bronchiectasis group, and were positively correlated with SPAP (p < 0.0001) and
      negatively correlated with Pao2 (p < 0.016). Other hemodynamic variables were not
      different between groups. PH in 31 patients (32.9%) was significantly greater in
      patients with cystic bronchiectasis compared with cylindrical bronchiectasis (p =
      0.04). In cystic bronchiectasis, SPAP was positively correlated with Paco2 (p =
      0.001), and inversely correlated with Pao2 (p = 0.03), diffusion capacity of the
      lung for carbon monoxide percentage (p = 0.02), and FEV1 (p = 0.02). CONCLUSIONS:
      RV systolic dysfunction and PH were more common than LV systolic dysfunction in
      bronchiectatic patients. LV diastolic dysfunction was mainly seen in severe PH.
      We recommend detailed assessment of cardiac function, particularly LV diastolic
      function, in patients with bronchiectasis.

PMID- 18071020
TI  - Physiologic benefits of mechanical insufflation-exsufflation in children with
      neuromuscular diseases.
AB  - STUDY OBJECTIVES: To analyze the physiologic effects and tolerance of mechanical
      insufflation-exsufflation (MI-E) by means of mechanical cough assistance (Cough
      Assist; JH Emerson Company; Cambridge, MA) for children with neuromuscular
      disease. DESIGN: Prospective clinical trial. SETTING: Physiology laboratory of a
      pediatric pulmonary department of a university hospital. PATIENTS: Seventeen
      children with Duchenne muscular dystrophy (n = 4), spinal muscular atrophy (n =
      4), or other congenital myopathy (n = 9) who were in a stable state.
      INTERVENTIONS: Pressures of 15, 30, and 40 cm H(2)O were cycled to each patient,
      with 2 s for insufflation and 3 s for exsufflation. One application consisted of
      six cycles at each pressure for a total of three applications. MEASUREMENTS AND
      RESULTS: Airway pressure and airflow were measured during every application.
      Breathing pattern, vital capacity (VC), sniff nasal inspiratory pressure (SNIP),
      peak expiratory flow (PEF), and respiratory comfort were evaluated at baseline
      and after each application. The tolerance of the patients was excellent, with a
      significant increase in the respiratory comfort score in all of the patients (p =
      0.02). Expired volume during the MI-E application increased significantly to
      reach twice the VC at 40 cm H(2)O. Mean and maximal inspiratory and expiratory
      flows increased in a pressure-dependent manner. Breathing pattern did not change
      after the MI-E applications and pulse oximetric saturation remained stable within
      normal values, but the mean end-tidal carbon dioxide pressure decreased
      significantly. VC did not change, but the mean SNIP and PEF improved
      significantly after MI-E applications. CONCLUSIONS: Our results confirm the good
      tolerance and physiologic short-term benefit of the MI-E in children with
      neuromuscular disease who were in a stable state.

PMID- 18071021
TI  - Increased survival with mechanical ventilation in posttuberculosis patients with
      the combination of respiratory failure and chest wall deformity.
AB  - BACKGROUND: Patients who have had tuberculosis are at risk for respiratory
      failure with hypercapnea from chest wall deformity and hypoxia from pulmonary
      sequelae. The combination of hypercapnea and hypoxia justifies both mechanical
      ventilation and oxygen therapy as treatment options. We aimed to study which
      treatment mode is associated with the best survival in patients with the
      combination of respiratory failure and chest wall deformity from tuberculosis.
      METHODS: Swedish patients starting oxygen therapy or mechanical ventilation
      between 1996 and 2004 due to the combination of respiratory failure and chest
      wall deformity from tuberculosis were eligible for conclusion. They were followed
      up prospectively until October 2006, with death as the primary outcome. RESULTS:
      A cohort of 188 patients was included. Eighty-five patients received mechanical
      ventilation, and 103 received oxygen therapy alone. No patients were excluded,
      and no patients were unavailable for follow-up. Mechanical ventilation was
      associated with a significantly better survival than oxygen therapy alone, even
      after adjustments for age, gender, concomitant respiratory disease, blood gas
      tensions, and vital capacity, with an adjusted hazard risk of death of 0.35 (95%
      confidence interval, 0.17 to 0.70). CONCLUSION: Patients with the combination of
      respiratory failure and chest wall deformity from tuberculosis had a
      significantly better survival when treated with home mechanical ventilation than
      with long-term oxygen therapy alone. We recommend home mechanical ventilation
      with or without supplementary oxygen as the first choice of treatment for these
      patients.

PMID- 18071022
TI  - Impact of cough across different chronic respiratory diseases: comparison of two
      cough-specific health-related quality of life questionnaires.
AB  - BACKGROUND: Cough is a prominent symptom across a range of common chronic
      respiratory diseases and impacts considerably on patient health status. METHODS:
      We undertook a cross-sectional comparison of scores from two cough-specific
      health-related quality of life (HRQoL) questionnaires, the Leicester Cough
      Questionnaire (LCQ), and the Cough Quality of Life Questionnaire (CQLQ), together
      with a generic HRQoL measure, the EuroQol. Questionnaires were administered to
      and spirometry performed on 147 outpatients with chronic cough (n = 83), COPD (n
      = 18), asthma (n = 20), and bronchiectasis (n = 26). RESULTS: There was no
      significant difference in the LCQ and CQLQ total scores between groups (p = 0.24
      and p = 0.26, respectively). Exploratory analyses of questionnaire subdomains
      revealed differences in psychosocial issues and functional impairment between the
      four groups (p = 0.01 and p = 0.05, respectively). CQLQ scores indicated that
      chronic coughers have more psychosocial issues than patients with bronchiectasis
      (p = 0.03) but less functional impairment than COPD patients (p = 0.04). There
      was a significant difference in generic health status across the four disease
      groups (p = 0.04), with poorest health status in COPD patients. A significant
      inverse correlation was observed between CQLQ and LCQ in each disease group
      (chronic cough r = - 0.56, p < 0.001; COPD r = - 0.49, p = 0.04; asthma r = -
      0.94, p < 0.001; and bronchiectasis r = - 0.88, p < 0.001). There was no
      correlation between cough questionnaire scores and FEV(1) in any group, although
      a significant correlation between EuroQol visual analog scale component and
      FEV(1) (r = 0.639, p = 0.004) was observed in COPD patients. CONCLUSION: Cough
      adversely affects health status across a range of common respiratory diseases.
      The LCQ and CQLQ can each provide important additional information concerning the
      impact of cough.

PMID- 18071023
TI  - Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated
      interstitial lung disease.
AB  - OBJECTIVE: We sought to determine the effectiveness of mycophenolate mofetil
      (MMF) in scleroderma- associated interstitial lung disease (SSc-ILD). METHODS: We
      retrospectively identified patients who met criteria for systemic sclerosis, had
      evidence of SSc-ILD on chest CT, received > 1 g/d of MMF for >or= 6 months, and
      had pulmonary function data available. Vital capacity (VC) and diffusion capacity
      of the lung for carbon monoxide (Dlco) at treatment onset were compared with VC
      and Dlco values 12 months before and 12 months after treatment onset. Twelve
      month values were imputed from regression lines generated using all VC and Dlco
      measurements made in the 24-month period either prior to or following treatment
      onset. RESULTS: Among 13 patients who met inclusion criteria, MMF was associated
      with a significant improvement in VC (mean, + 159 mL; confidence interval [CI], +
      30 to + 289 mL; and + 4% of the predicted normal value; CI, + 2 to + 7%) after 12
      months of treatment. In contrast, patients had a significant decrease in VC
      (mean, - 239 mL; CI, - 477 to - 0.5 mL; and - 5% of the predicted normal value;
      CI, - 11 to - 0.3%) in the 12 months prior to MMF treatment. Dlco did not change
      significantly during MMF treatment (mean, + 1% of the predicted normal value; CI,
      - 2 to + 5%) but decreased significantly in the 12 months prior to treatment
      (mean, - 5% of the predicted normal value; CI, - 10 to - 1%). CONCLUSION: These
      retrospective data suggest MMF improves VC in patients with SSc-ILD.

PMID- 18071024
TI  - Defining pancreatic endocrine precursors and their descendants.
AB  - OBJECTIVE: The global incidence of diabetes continues to increase. Cell
      replacement therapy and islet transplantation offer hope, especially for severely
      affected patients. Efforts to differentiate insulin-producing beta-cells from
      progenitor or stem cells require knowledge of the transcriptional programs that
      regulate the development of the endocrine pancreas. RESEARCH DESIGN AND METHODS:
      Differentiation toward the endocrine lineage is dependent on the transcription
      factor Neurogenin 3 (Neurog3, Ngn3). We utilize a Neurog3-enhanced green
      fluorescent protein knock-in mouse model to isolate endocrine progenitor cells
      from embryonic pancreata (embryonic day [E]13.5 through E17.5). Using advanced
      genomic approaches, we generate a comprehensive gene expression profile of these
      progenitors and their immediate descendants. RESULTS: A total of 1,029 genes were
      identified as being temporally regulated in the endocrine lineage during fetal
      development, 237 of which are transcriptional regulators. Through pathway
      analysis, we have modeled regulatory networks involving these proteins that
      highlight the complex transcriptional hierarchy governing endocrine
      differentiation. CONCLUSIONS: We have been able to accurately capture the gene
      expression profile of the pancreatic endocrine progenitors and their descendants.
      The list of temporally regulated genes identified in fetal endocrine precursors
      and their immediate descendants provides a novel and important resource for
      developmental biologists and diabetes researchers alike.

PMID- 18071025
TI  - The ENPP1 K121Q polymorphism is associated with type 2 diabetes in European
      populations: evidence from an updated meta-analysis in 42,042 subjects.
AB  - OBJECTIVE: Functional studies suggest that the nonsynonymous K121Q polymorphism
      in the ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) may confer
      susceptibility to insulin resistance; genetic evidence on its effect on type 2
      diabetes, however, has been conflicting. We therefore conducted a new meta
      analysis that includes novel unpublished data from the ENPP1 Consortium and
      recent negative findings from large association studies to address the
      contribution of K121Q to type 2 diabetes. RESEARCH DESIGN AND METHODS: After a
      systematic review of the literature, we evaluated the effect of ENPP1 K121Q on
      diabetes risk under three genetic models using a random-effects approach. Our
      primary analysis consisted of 30 studies comprising 15,801 case and 26,241
      control subjects. Due to considerable heterogeneity and large differences in
      allele frequencies across populations, we limited our meta-analysis to those of
      self-reported European descent and, when available, included BMI as a covariate.
      RESULTS: We found a modest increase in risk of type 2 diabetes for QQ homozygotes
      in white populations (combined odds ratio [OR] 1.38 [95% CI 1.10-1.74], P =
      0.005). There was no evidence of publication bias, but we noted significant
      residual heterogeneity among studies (P = 0.02). On meta-regression, 16% of the
      effect was accounted for by the mean BMI of control subjects. This association
      was stronger in studies in which control subjects were leaner but disappeared
      after adjustment for mean control BMI (combined OR 0.93 [95% CI 0.75-1.15], P =
      0.50). CONCLUSIONS: The ENPP1 Q121 variant increases risk of type 2 diabetes
      under a recessive model of inheritance in whites, an effect that appears to be
      modulated by BMI.

PMID- 18071026
TI  - Transcription factor 7-like 2 regulates beta-cell survival and function in human
      pancreatic islets.
AB  - OBJECTIVE: Type 2 diabetes is characterized by impaired insulin secretion in
      response to increased metabolic demand. This defect in beta-cell compensation
      seems to result from the interplay between environmental factors and genetic
      predisposition. Genome-wide association studies reveal that common variants in
      transcription factor 7-like 2 (TCF7L2) are associated with increased risk of type
      2 diabetes. The aim of the present study was to establish whether TCF7L2 plays a
      role in beta-cell function and/or survival. RESEARCH DESIGN AND METHODS: To
      investigate the effects of TCFL7L2 depletion, isolated islets were exposed to
      TCF7L2 small interfering RNA (siRNA) versus scrambled siRNA, and beta-cell
      survival and function were examined. For TCF7L2 overexpression, islets were
      cultured in glucose concentrations of 5.5-33.3 mmol/l and the cytokine mix
      interleukin-1 beta/gamma-interferon with or without overexpression of TCF7L2.
      Subsequently, glucose-stimulated insulin secretion (GSIS), beta-cell apoptosis
      [by transferase-mediated dUTP nick-end labeling assay and Western blotting for
      poly(ADP-ribose) polymerase and Caspase-3 cleavage], and beta-cell proliferation
      (by Ki67 immunostaining) were analyzed. RESULTS: Depleting TCF7L2 by siRNA
      resulted in a 5.1-fold increase in beta-cell apoptosis, 2.2-fold decrease in beta
      cell proliferation (P < 0.001), and 2.6-fold decrease in GSIS (P < 0.01) in human
      islets. Similarly, loss of TCF7L2 resulted in impaired beta-cell function in
      mouse islets. In contrast, overexpression of TCF7L2 protected islets from glucose
      and cytokine-induced apoptosis and impaired function. CONCLUSIONS: TCF7L2 is
      required for maintaining GSIS and beta-cell survival. Changes in the level of
      active TCF7L2 in beta-cells from carriers of at-risk allele may be the reason for
      defective insulin secretion and progression of type 2 diabetes.

PMID- 18071027
TI  - Genetic variation and association analyses of the nuclear respiratory factor 1
      (nRF1) gene in Chinese patients with type 2 diabetes.
AB  - OBJECTIVE: Nuclear respiratory factor 1 (NRF1) is a strong biological and
      positional candidate to contribute to type 2 diabetes susceptibility. This study
      aimed at evaluating associations between NRF1 genetic polymorphisms and
      development of type 2 diabetes. RESEARCH DESIGN AND METHODS: Using a variation
      screening approach, 6 novel and 10 known single nucleotide polymorphisms (SNPs)
      in the NRF1 gene were identified. Nine SNPs were then selected using pairwise
      tagging with an r(2) cutoff of 0.8 and/or minor allele frequency of >5% and
      genotyped in 596 type 2 diabetic patients and 431 nondiabetic subjects, all of
      whom were Han Chinese. RESULTS: Two novel SNPs (-46127T>C and +98560A>G) were
      associated with type 2 diabetes (P = 0.018 and 0.036; for possession of minor
      allele, odds ratio [OR] 0.620 and 3.199, with dominant model and correction for
      multiple comparisons). In SNP rs1882094 (+141G>T), the nondiabetic control
      subjects carrying GG genotype had lower fasting plasma glucose levels than
      carriers with other genotypes (P = 0.0002). One common haplotype (H2) mainly
      composed of SNPs rs6969098 (-24833 A>G), rs1882094, and another novel variant
      (+97884G>A) was significantly associated with type 2 diabetes (P = 0.016, OR
      0.706). Subjects with this haplotype had lower fasting triglyceride levels when
      compared with those with other haplotypes (P = 0.010). CONCLUSIONS: The present
      study shows an association of SNPs in the NRF1 gene with type 2 diabetes in a Han
      Chinese population. NRF1 genetic polymorphisms may be a suspectibility factor for
      type 2 diabetes by conferring abnormalities in triglyceride metabolism. Further
      studies should replicate this finding using larger and racially diverse
      populations.

PMID- 18071028
TI  - Resolving the structural features of genomic islands: a machine learning
      approach.
AB  - Large inserts of horizontally acquired DNA that contain functionally related
      genes with limited phylogenetic distribution are often referred to as genomic
      islands (GIs), and structural definitions of these islands, based on common
      features, have been proposed. Although a large number of mobile elements fall
      well within the GI definition, there are several concerns about the structural
      consensus for GIs: The current GI definition was put forward 10 yr ago when only
      12 complete bacterial genomes were available, a large number of GIs deviate from
      that definition, and in silico predictions assuming a full/partial GI structural
      model bias the sampling of the GI structural space toward "well-structured" GIs.
      In this study, the structural features of genomic regions are sampled by a
      hypothesis-free, bottom-up search, and these are exploited in a machine learning
      approach with the aim of explicitly quantifying and modeling the contribution of
      each feature to the GI structure. Performing a whole-genome-based comparative
      analysis between 37 strains of three different genera and 12 outgroup genomes,
      668 genomic regions were sampled and used to train structural GI models. The data
      show that, overall, GIs from the three different genera fall into distinct, genus
      specific structural families. However, decreasing the taxa resolution, by
      studying GI structures across different genus boundaries, provides models that
      converge on a fairly similar GI structure, further suggesting that GIs can be
      seen as a superfamily of mobile elements, with core and variable structural
      features, rather than a well-defined family.

PMID- 18071029
TI  - Metrics of sequence constraint overlook regulatory sequences in an exhaustive
      analysis at phox2b.
AB  - Despite its recognized utility, the extent to which evolutionary sequence
      conservation-based approaches may systematically overlook functional noncoding
      sequences remains unclear. We have tiled across sequence encompassing the
      zebrafish phox2b gene, ultimately evaluating 48 amplicons corresponding to all
      noncoding sequences therein for enhancer activity in zebrafish. Post hoc analyses
      of this interval utilizing five commonly used measures of evolutionary constraint
      (AVID, MLAGAN, SLAGAN, phastCons, WebMCS) demonstrate that each systematically
      overlooks regulatory sequences. These established algorithms detected only 29%
      61% of our identified regulatory elements, consistent with the suggestion that
      many regulatory sequences may not be readily detected by metrics of sequence
      constraint. However, we were able to discriminate functional from nonfunctional
      sequences based upon GC composition and identified position weight matrices
      (PWM), demonstrating that, in at least one case, deleting sequences containing a
      subset of these PWMs from one identified regulatory element abrogated its
      regulatory function. Collectively, these data demonstrate that the noncoding
      functional component of vertebrate genomes may far exceed estimates predicated on
      evolutionary constraint.

PMID- 18071030
TI  - Combination therapy with interferon beta-1a and doxycycline in multiple
      sclerosis: an open-label trial.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and tolerability of combination
      therapy with intramuscular interferon beta-1a and oral doxycycline, a potent
      inhibitor of matrix metalloproteinases, in patients with relapsing-remitting
      multiple sclerosis (RRMS) having breakthrough disease activity. DESIGN: Open
      label, 7-month trial. SETTING: Louisiana State University Health Sciences Center,
      Shreveport. PATIENTS: Fifteen patients with RRMS taking interferon beta-1a with
      breakthrough disease activity took doxycycline for 4 months. Patients underwent
      monthly neurologic examination, magnetic resonance imaging of the brain using
      triple-dose gadolinium, and safety blood work. INTERVENTIONS: Ongoing treatment
      with intramuscular interferon beta-1a plus oral doxycycline, 100 mg daily, for 4
      months. MAIN OUTCOME MEASURES: The primary end point was gadolinium-enhancing
      lesion number change, and the secondary end points were relapse rates, safety and
      tolerability of the combination of interferon beta-1a and doxycycline in patients
      with MS, Expanded Disability Status Scale score, serum matrix metalloproteinase-9
      levels, and transendothelial migration of monocytes exposed to serum from
      patients with RRMS. RESULTS: Combination of doxycycline and interferon beta-1a
      treatment resulted in reductions in contrast-enhancing lesion numbers and
      posttreatment Expanded Disability Status Scale values (P < .001 for both). Only 1
      patient relapsed. Multivariate analyses indicated correlations between decreased
      serum matrix metalloproteinase-9 levels and enhancing lesion activity reduction.
      Transendothelial migration of monocytes incubated with serum from patients with
      RRMS undergoing combination therapy was suppressed. Adverse effects were mild; no
      adverse synergistic effects of combination therapy or unexpected adverse events
      were reported. CONCLUSIONS: Combination of intramuscular interferon beta-1a and
      oral doxycycline treatment was effective, safe, and well tolerated. Controlled
      clinical trials in larger cohorts of patients with MS are needed to evaluate the
      efficacy and tolerability of this combination. Trial Registration
      clinicaltrials.gov Identifier: NCT00246324

PMID- 18071031
TI  - The wind of change.

PMID- 18071032
TI  - Mapping Africa's way into prominence in the field of neurology.
AB  - Although neurology originated in Africa, there is little modern African
      contribution to the advancement of knowledge in this field. We present the
      African neurologic service and scientific productivity indices and suggest a
      development plan. We conducted PubMed and EMBASE searches for articles about
      neurologic services in Africa. To assess scientific productivity, we determined
      the number of publications of African origin in journals with high impact. The
      neurologist-population ratio in African countries varies from 1 per 162,885
      persons to none in 11 countries, compared with 1 per 29,200 persons in the United
      States. There are few African publications in high-impact international journals
      of neurology. Africa faces a heavy burden of communicable diseases and increasing
      noncommunicable diseases, with few workers, poor equipment, and little research
      effort to bear it. There is a need for African neuroscientists to discover areas
      of research unique to the continent in order to advance the frontiers of
      knowledge for all neurologists. International collaboration and support are
      required to improve the number of workers, resources, and research productivity.

PMID- 18071033
TI  - Functional implication of the vitamin A signaling pathway in the brain.
AB  - Vitamin A is necessary for normal embryonic development, but its role in the
      adult brain is poorly understood. Vitamin A derivatives, retinoids, are involved
      in a complex signaling pathway that regulates gene expression and, in the central
      nervous system, controls neuronal differentiation and neural tube patterning.
      Although a major functional implication of retinoic signaling has been repeatedly
      suggested in synaptic plasticity, learning and memory, sleep, schizophrenia,
      depression, Parkinson disease, and Alzheimer disease, the targets and the
      underlying mechanisms in the adult brain remain elusive.

PMID- 18071034
TI  - Heart valve regurgitation, pergolide use, and parkinson disease: an observational
      study and meta-analysis.
AB  - OBJECTIVE: To investigate the prevalence and risk factors of heart valve disease
      in patients having PD treated with pergolide. DESIGN: Prospective observational
      study. SETTING: Patients were recruited at the Hopital de la Pitie-Salpetriere,
      Paris, France. Patients Ninety-six patients having PD treated with pergolide for
      longer than 3 months vs 50 control subjects. Intervention Standardized
      echocardiography performed by an investigator blinded to treatment status. Main
      Outcome Measure Moderate to severe regurgitation in at least 1 heart valve.
      RESULTS: One hundred thirty-three echocardiograms (86 in the pergolide-treated
      group and 47 in the control group) were analyzed in the study. Moderate to severe
      regurgitation was found in 15 patients treated with pergolide (17.4%) and in 2
      control subjects (4.3%) (odds ratio [OR], 4.75; 95% confidence interval [CI],
      1.02-22.1; P = .03). Moderate to severe regurgitation was associated with the
      cumulative dose of pergolide (OR, 1.37; 95% CI, 1.04-1.81 per 10-mg/kg increase;
      P =.03). Including the present study, the meta-analysis comprised 7 trials (394
      patients treated with pergolide and 280 controls). The overall OR for moderate to
      severe regurgitation was 3.1 (95% CI, 1.7-5.6; P < .001) in the pergolide-treated
      group. Risk differences were correlated with the mean cumulative dose of
      pergolide (r = 0.90, P < .001). DATA SOURCES: Using an end point of moderate to
      severe heart valve regurgitation, we performed a meta-analysis of patients having
      Parkinson disease (PD) treated with pergolide mesylate vs control subjects by
      searching PubMed (January 1, 1966, to April 1, 2007) and the Cochrane databases
      to identify English-language prospective observational studies that reported
      echocardiographic data. CONCLUSION: Heart valve disease is independently
      associated with the use of pergolide treatment in patients having PD and
      correlates with its cumulative dose. Trial Registration clinicaltrials.gov
      Identifier: NCT00202657.

PMID- 18071035
TI  - Polygenic disease associations in thymomatous myasthenia gravis.
AB  - BACKGROUND: Relevant genetic markers for myasthenia gravis (MG) include tumor
      necrosis factors alpha and beta, Fcgamma receptor IIa, and interleukin 10. The
      corresponding gene products are thought to be involved in MG pathogenesis.
      OBJECTIVES: To investigate whether MG susceptibility correlates with specific
      combinations of genetic markers and to compare the contribution of each marker.
      PARTICIPANTS: Forty-seven patients with MG and 92 healthy blood donors. MAIN
      OUTCOME MEASURES: Presence of tumor necrosis factors alpha and beta, Fcgamma
      receptor IIa, and interleukin 10 genotypes and autoantibodies against nicotinic
      acetylcholine receptor, titin, and ryanodine receptor. RESULTS: Susceptibility to
      MG increases with an increasing number of genetic markers in both thymomatous MG
      and MG with titin antibodies but not in early-onset MG. In thymomatous MG,
      Fcgamma receptor IIa allelic variants seem to be the most important determinant
      of disease. CONCLUSION: Specific combinations of allelic variants individually
      associated with MG synergize in predisposing to thymomatous MG and MG with titin
      antibodies.

PMID- 18071037
TI  - Variability of age at onset in siblings with familial Alzheimer disease.
AB  - BACKGROUND: Variability of age at onset (AO) of Alzheimer disease (AD) among
      members of the same family is important as a biological clue and because of its
      clinical effects. OBJECTIVE: To evaluate which clinical variables influence the
      discrepancy in AO among affected relatives with familial AD. SETTING: Clinical
      genetic project of Spanish kindred with AD conducted by 4 academic hospitals in
      Madrid, Spain. METHODS: Age at onset of AD in 162 families and discrepancy in AO
      in intragenerational and intergenerational affected pairs were analyzed in
      relation to age, sex, maternal or paternal transmission, pattern of inheritance,
      and apolipoprotein E genotype. RESULTS: Maternal transmission of AD was
      significantly more frequent than paternal transmission (P < .001). In 27% of the
      affected individuals, AO occurred before the patient was 65 years old.
      Discrepancy in AO among siblings was within 5 years in 44% of the families, 6 to
      10 years in 29%, and more than 10 years in 27% (range, 0-22). This discrepancy
      was independent of the sex of the sibling pairs and was significantly lower with
      maternal transmission of AD (P = .02). Segregation analysis showed no differences
      in the inheritance pattern between families with low (< or =5 years) or high (>5
      years) AO discrepancy. Age at onset in carriers of the apolipoprotein E epsilon4
      allele was slightly younger. However, among siblings, an extra apolipoprotein E
      epsilon4 allele was not consistently associated with earlier onset of AD. Eighty
      percent of patients, independent of sex or mode of transmission, were already
      affected at their parents' reported AO. CONCLUSIONS: There is a wide discrepancy
      in AO in affected siblings that is not clearly explained by a single clinical
      variable or apolipoprotein E genotype. The interaction of many factors probably
      determines AO in each affected individual. However, maternal transmission of AD
      seems to result in a similar AO in offspring, and the risk of developing dementia
      after the parent's reported AO decreases significantly.

PMID- 18071036
TI  - Hypertension and the risk of mild cognitive impairment.
AB  - OBJECTIVE: To explore whether hypertension is associated with the risk of mild
      cognitive impairment (MCI), an intermediate stage of dementia, because there are
      conflicting data relating hypertension to the risk of Alzheimer disease. DESIGN
      AND SETTING: Prospective community-based cohort study conducted in northern
      Manhattan. Multivariate proportional hazards regression analyses were used,
      relating hypertension to incident all-cause MCI, amnestic MCI, and nonamnestic
      MCI in 918 persons without prevalent MCI at baseline followed up for a mean of
      4.7 years. RESULTS: There were 334 cases of incident MCI, 160 cases of amnestic
      MCI, and 174 cases of nonamnestic MCI during 4337 person-years of follow-up.
      Hypertension was associated with an increased risk of all-cause MCI (hazard
      ratio, 1.40; 95% confidence interval, 1.06-1.77; P = .02) and nonamnestic MCI
      (hazard ratio, 1.70; 95% confidence interval, 1.13-2.42; P = .009) after
      adjusting for age and sex. Both associations were slightly attenuated in models
      additionally adjusting for stroke and other vascular risk factors. There was no
      association between hypertension and the risk of amnestic MCI (hazard ratio,
      1.10; 95% confidence interval, 0.79-1.63; P = .49). Consistent with this
      association, hypertension was related with the slope of change in an executive
      ability score, but not with memory or language score. There was no effect
      modification of the association between hypertension and MCI by APOEepsilon4
      genotype or use of antihypertensive medication. CONCLUSIONS: A history of
      hypertension is related to a higher risk of MCI. The association seems to be
      stronger with the nonamnestic than the amnestic type of MCI in the elderly. These
      findings suggest that prevention and treatment of hypertension may have an
      important impact in lowering the risk of cognitive impairment.

PMID- 18071038
TI  - Leisure activity and cognitive decline in incident Alzheimer disease.
AB  - BACKGROUND: High rates of leisure activity have been associated with reduced risk
      of Alzheimer disease (AD). OBJECTIVE: To determine whether prediagnosis leisure
      activity modifies the rate of cognitive decline in patients with AD. DESIGN:
      Inception cohort followed up longitudinally for a mean of 5.3 years (up to 13.9
      years). SETTING: Urban community. PARTICIPANTS: A total of 283 patients with
      incident AD (mean age, 79 years; 56.2% Hispanic and 31.1% African American). MAIN
      OUTCOME MEASURES: Change in a composite cognitive score from diagnosis on and
      during the entire study follow-up. RESULTS: In multivariate-adjusted generalized
      estimating equation models of postdiagnosis change (n = 133), each leisure
      activity was associated with an additional yearly decline of 0.005 of a z-score
      unit in cognitive score (P = .17). In models expanded to include cognitive change
      during study follow-up, including evaluations before and after diagnosis (n =
      283), each activity was associated with an additional yearly decline of 0.005 of
      a z-score unit in cognitive score (P = .03). The association was strongest for
      intellectual activities. CONCLUSIONS: Greater participation in prediagnosis
      leisure activities, especially intellectual activities, was associated with
      faster cognitive decline, supporting the hypothesis that the disease course in AD
      may vary as a function of cognitive reserve.

PMID- 18071039
TI  - Disruptive behavior as a predictor in Alzheimer disease.
AB  - BACKGROUND: Disruptive behavior is common in Alzheimer disease (AD). There are
      conflicting reports regarding its ability to predict cognitive decline,
      functional decline, institutionalization, and mortality. OBJECTIVE: To examine
      whether the presence of disruptive behavior has predictive value for important
      outcomes in AD. DESIGN: Using the Columbia University Scale for Psychopathology
      in Alzheimer Disease (administered every 6 months, for a total of 3438 visit
      assessments and an average of 6.9 per patient), the presence of disruptive
      behavior (wandering, verbal outbursts, physical threats/violence,
      agitation/restlessness, and sundowning) was extracted and examined as a time
      dependent predictor in Cox models. The models controlled for the recruitment
      cohort, recruitment center, informant status, sex, age, education, a comorbidity
      index, baseline cognitive and functional performance, and neuroleptic use.
      SETTING: Five university-based AD centers in the United States and Europe
      (Predictors Study). PARTICIPANTS: Four hundred ninety-seven patients with early
      stage AD (mean Folstein Mini-Mental State Examination score, 20 of 30 at entry)
      who were recruited and who underwent semiannual follow-up for as long as 14
      (mean, 4.4) years. MAIN OUTCOME MEASURES: Cognitive (Columbia Mini-Mental State
      Examination score, < or = 20 of 57 [approximate Folstein Mini-Mental State
      Examination score, < or = 10 of 30]) and functional (Blessed Dementia Rating
      Scale score, parts I and II, > or = 10) ratings, institutionalization equivalent
      index, and death. RESULTS: At least 1 disruptive behavioral symptom was noted in
      48% of patients at baseline and in 83% at any evaluation. Their presence was
      associated with increased risks of cognitive decline (hazard ratio 1.45 [95%
      confidence interval (CI), 1.03-2.03]), functional decline (1.66 [95% CI, 1.17
      2.36]), and institutionalization (1.47 [95% CI, 1.10-1.97]). Sundowning was
      associated with faster cognitive decline, wandering with faster functional
      decline and institutionalization, and agitation/restlessness with faster
      cognitive and functional decline. There was no association between disruptive
      behavior and mortality (hazard ratio, 0.94 [95% CI, 0.71-1.25]). CONCLUSION:
      Disruptive behavior is very common in AD and predicts cognitive decline,
      functional decline, and institutionalization but not mortality.

PMID- 18071040
TI  - Capgras syndrome and its relationship to neurodegenerative disease.
AB  - BACKGROUND: Capgras syndrome is characterized by a delusional belief that a
      person has been replaced by an imposter. It has been described in psychiatric and
      neurological (neurodegenerative and nonneurodegenerative) diseases. OBJECTIVES:
      To determine whether the clinical and demographic features of subjects with
      Capgras syndrome differ when the syndrome is associated with neurodegenerative
      compared with nonneurodegenerative diseases, and whether features differ across
      different neurodegenerative diseases. DESIGN: Retrospective study. SETTING:
      Tertiary care medical center. Patients Forty-seven subjects with Capgras
      syndrome. RESULTS: Thirty-eight of the subjects with Capgras syndrome (81%) had a
      neurodegenerative disease, most commonly Lewy body disease. Capgras syndrome
      occurred at a younger age of onset in those with a nonneurodegenerative disease
      (51 vs 72 years) (P < .001) co-occurring with paranoid schizophrenia,
      schizoaffective disorder, and methamphetamine abuse and immediately after
      cerebrovascular events. Of those with Capgras syndrome and Lewy body disease,
      100% had visual hallucinations compared with only one of those with Alzheimer
      disease (14%). CONCLUSIONS: Capgras syndrome is more commonly associated with
      neurodegenerative diseases, especially Lewy body disease, where visual
      hallucinations always coexist. In the absence of a neurodegenerative disease, the
      onset of Capgras syndrome occurs at a significantly younger age and can be
      associated with psychiatric disease, cerebrovascular events, and illicit drug
      use.

PMID- 18071041
TI  - Chronic pain in Machado-Joseph disease: a frequent and disabling symptom.
AB  - BACKGROUND: Machado-Joseph disease (MJD) is one of the most common forms of
      neurodegenerative ataxia characterized by remarkable phenotypic heterogeneity.
      Although patients frequently report pain, systematic evaluation of this clinical
      feature is lacking. OBJECTIVES: To compare the frequency of chronic pain among
      patients with genetically confirmed MJD, an age- and sex-matched healthy control
      group, and a disease control group of patients with amyotrophic lateral sclerosis
      (ALS). METHODS: We included 70 patients with MJD, 20 patients with ALS, and 70
      control subjects from 2 clinical centers. All individuals underwent assessment
      with a standardized pain questionnaire. In addition, we used a visual analog
      scale to quantify pain intensity. RESULTS: Thirty-three patients with MJD (47%),
      3 patients with ALS (15%), and 6 controls (9%) reported chronic pain. Lower back
      pain preceded ataxia in 6 patients with MJD. Twenty-nine patients with MJD had
      daily pain, which was continuous in 23. The mean visual analog scale score was
      6.1 in patients with MJD. Pain was musculoskeletal in 26 patients with MJD,
      dystonic in 2, neuropathic in 2, and mixed in 3. Typically, pain was lumbar (n =
      17) or in the lower limbs (n = 15). We did not find significant differences
      regarding duration of disease, sex, or severity of ataxia among patients with MJD
      with and without chronic pain. Expanded (CAG)(n) tandem repeats were longer in
      patients with MJD who experienced chronic pain (67.3 vs 65.2; P = .04).
      CONCLUSIONS: In our series, pain was significantly more frequent in patients with
      MJD than in controls. Chronic pain was a frequent and often disabling complaint
      among patients with MJD. The lower back was the most frequently reported location
      of pain in patients with MJD.

PMID- 18071043
TI  - Fatal initial adult-onset presentation of urea cycle defect.
AB  - BACKGROUND: Ornithine transcarbamylase (OTC) deficiency presents most commonly
      with neonatal hyperammonemic coma. The gene is on the X chromosome, but the
      disease may manifest as a dominant trait. Mutations that lead to later-onset
      presentations may lead to life-threatening disease and may be unrecognized,
      particularly when the first clinical disease occurs in adulthood. OBJECTIVE: To
      document the clinical and metabolic consequences of a mutation in the OTC gene.
      DESIGN: Case reports. SETTING: A metabolic/biochemical genetic referral service.
      MAIN OUTCOME MEASURES: Clinical and biochemical observations in 3 generations of
      a family. RESULTS: A mutation in codon 208 of exon 6 in the OTC gene was found in
      a family in which the proband died of hyperammonemia at 52 years of age.
      CONCLUSIONS: Diagnosis of late-onset presentations of urea cycle defect in adults
      may be delayed. Heightened awareness could lead to effective treatment.

PMID- 18071042
TI  - Alpha7 nicotinic receptor up-regulation in cholinergic basal forebrain neurons in
      Alzheimer disease.
AB  - BACKGROUND: Dysfunction of basocortical cholinergic projection neurons of the
      nucleus basalis (NB) correlates with cognitive deficits in Alzheimer disease
      (AD). Nucleus basalis neurons receive cholinergic inputs and express nicotinic
      acetylcholine receptors (nAChRs) and muscarinic AChRs (mAChRs), which may
      regulate NB neuron activity in AD. Although alterations in these AChRs occur in
      the AD cortex, there is little information detailing whether defects in nAChR and
      mAChR gene expression occur in cholinergic NB neurons during disease progression.
      OBJECTIVE: To determine whether nAChR and mAChR gene expression is altered in
      cholinergic NB neurons during the progression of AD. DESIGN: Individual NB
      neurons from subjects diagnosed ante mortem as having no cognitive impairment
      (NCI), mild cognitive impairment (MCI), or mild to moderate AD were analyzed by
      single-cell AChR expression profiling via custom-designed microarrays. SETTING:
      Academic research. PARTICIPANTS: Participants were members of the Rush Religious
      Orders Study cohort. MAIN OUTCOME MEASURES: Real-time quantitative polymerase
      chain reaction was performed to validate microarray findings. RESULTS:
      Cholinergic NB neurons displayed a statistically significant up-regulation of
      alpha7 nAChR messenger RNA expression in subjects with mild to moderate AD
      compared with those with NCI and MCI (P<.001). No differences were found for
      other nAChR and mAChR subtypes across the cohort. Expression levels of alpha7
      nAChRs were inversely associated with Global Cognitive Score and with Mini-Mental
      State Examination performance. CONCLUSIONS: Up-regulation of alpha7 nAChRs may
      signal a compensatory response to maintain basocortical cholinergic activity
      during AD progression. Alternatively, putative competitive interactions of this
      receptor with beta-amyloid may provide a pathogenic mechanism for NB dysfunction.
      Increasing NB alpha7 nAChR expression may serve as a marker for the progression
      of AD.

PMID- 18071045
TI  - Acquired hypopigmentation (leukoderma) as a presenting feature of metastatic
      amelanotic melanoma with brain involvement.

PMID- 18071044
TI  - Creutzfeldt-Jakob disease, prion protein gene codon 129VV, and a novel PrPSc type
      in a young British woman.
AB  - BACKGROUND: Variant Creutzfeldt-Jakob disease (vCJD) is an acquired prion disease
      causally related to bovine spongiform encephalopathy that has occurred
      predominantly in young adults. All clinical cases studied have been methionine
      homozygotes at codon 129 of the prion protein gene (PRNP) with distinctive
      neuropathological findings and molecular strain type (PrP(Sc) type 4). Modeling
      studies in transgenic mice suggest that other PRNP genotypes will also be
      susceptible to infection with bovine spongiform encephalopathy prions but may
      develop distinctive phenotypes. OBJECTIVE: To describe the histopathologic and
      molecular investigation in a young British woman with atypical sporadic CJD and
      valine homozygosity at PRNP codon 129. DESIGN: Case report, autopsy, and
      molecular analysis. SETTING: Specialist neurology referral center, together with
      the laboratory services of the MRC [Medical Research Council] Prion Unit. Subject
      Single hospitalized patient. MAIN OUTCOME MEASURES: Autopsy findings and
      molecular investigation results. RESULTS: Autopsy findings were atypical of
      sporadic CJD, with marked gray and white matter degeneration and widespread prion
      protein (PrP) deposition. Lymphoreticular tissue was not available for analysis.
      Molecular analysis of PrP(Sc) (the scrapie isoform of PrP) from cerebellar tissue
      demonstrated a novel PrP(Sc) type similar to that seen in vCJD (PrP(Sc) type 4).
      However, this could be distinguished from the typical vCJD pattern by an altered
      protease cleavage site in the presence of the metal ion chelator EDTA.
      CONCLUSIONS: Further studies will be required to characterize the prion strain
      seen in this patient and to investigate its etiologic relationship with bovine
      spongiform encephalopathy. This case illustrates the importance of molecular
      analysis of prion disease, including the use of EDTA to investigate the metal
      dependence of protease cleavage patterns of PrP(Sc).

PMID- 18071046
TI  - Vasculitic presentation of staphylococcal meningitis.

PMID- 18071047
TI  - Ocular Myasthenia Gravis treatment: the case against prednisone therapy and
      thymectomy.

PMID- 18071048
TI  - Immunosuppressive or surgical treatment for ocular Myasthenia Gravis.

PMID- 18071049
TI  - Treating ocular Myasthenia Gravis with inadequate evidence.

PMID- 18071050
TI  - High-resolution ultrasound as a diagnostic adjunct in common peroneal neuropathy.

PMID- 18071051
TI  - Notice of redundant publication: "Transdermal rotigotine: double-blind, placebo
      controlled trial in Parkinson disease" (Arch Neurol. 2007;64[5]:676-682).

PMID- 18071052
TI  - More on multiple sclerosis and neuromyelitis optica.

PMID- 18071053
TI  - Activity-adjusted 24-hour ambulatory blood pressure and cardiac remodeling in
      children with sleep disordered breathing.
AB  - Questions remain as to whether pediatric sleep disordered breathing increases the
      risk for elevated blood pressure and blood pressure-dependent cardiac remodeling.
      We tested the hypothesis that activity-adjusted morning blood pressure surge,
      blood pressure load, and diurnal and nocturnal blood pressure are significantly
      higher in children with sleep disordered breathing than in healthy controls and
      that these blood pressure parameters relate to left ventricular remodeling. 24
      hour ambulatory blood pressure parameters were compared between groups. The
      associations between blood pressure and left ventricular relative wall thickness
      and mass were measured. 140 children met the inclusion criteria. In children with
      apnea hypopnea index <5 per hour, a significant difference from controls was the
      morning blood surge. Significant increases in blood pressure surge, blood
      pressure load, and in 24-hour ambulatory blood pressure were evident in those
      whom the apnea hypopnea index exceeded 5 per hour. Sleep disordered breathing and
      body mass index had similar effect on blood pressure parameters except for
      nocturnal diastolic blood pressure, where sleep disordered breathing had a
      significantly greater effect than body mass index. Diurnal and nocturnal systolic
      blood pressure, diastolic blood pressure, and mean arterial blood pressure
      predicted the changes in left ventricular relative wall thickness. Therefore,
      sleep disordered breathing in children who are otherwise healthy is independently
      associated with an increase in morning blood pressure surge, blood pressure load,
      and 24-hour ambulatory blood pressure. The association between left ventricular
      remodeling and 24-hour blood pressure highlights the role of sleep disordered
      breathing in increasing cardiovascular morbidity.

PMID- 18071054
TI  - Aortic diameter, wall stiffness, and wave reflection in systolic hypertension.
AB  - Systolic hypertension is associated with increased pulse pressure (PP) and
      increased risk for adverse cardiovascular outcomes. However the pathogenesis of
      increased PP remains controversial. One hypothesis suggests that aortic
      dilatation, wall stiffening and increased pulse wave velocity result from elastin
      fragmentation, leading to a premature reflected pressure wave that contributes to
      elevated PP. An alternative hypothesis suggests that increased proximal aortic
      stiffness and reduced aortic diameter leads to mismatch between pressure and
      flow, giving rise to an increased forward pressure wave and increased PP. To
      evaluate these two hypotheses, we measured pulsatile hemodynamics and proximal
      aortic diameter directly using tonometry, ultrasound imaging, and Doppler in 167
      individuals with systolic hypertension. Antihypertensive medications were
      withdrawn for at least 1 week before study. Patients with PP above the median (75
      mm Hg) had lower aortic diameter (2.94+/-0.36 versus 3.13+/-0.28 cm, P<0.001) and
      higher aortic wall stiffness (elastance-wall stiffness product: 16.1+/-0.7 versus
      15.7+/-0.7 ln[dyne/cm], P<0.001) with no difference in augmentation index (19.9+/
      10.4 versus 17.5+/-10.0%, P=0.12). Aortic diameter and wall stiffness both
      increased with advancing age (P<0.001). However, an inverse relation between PP
      and aortic diameter remained significant (P<0.001) in models that adjusted for
      age, sex, height, and weight and then further adjusted for aortic wall stiffness,
      augmentation index, and mean arterial pressure. Among individuals with systolic
      hypertension, increased PP is primarily attributable to increased wall stiffness
      and reduced aortic diameter rather than premature wave reflection.

PMID- 18071055
TI  - Physical activity and blood pressure in childhood: findings from a population
      based study.
AB  - The pathological processes associated with development of cardiovascular disease
      begin early in life. For example, elevated blood pressure (BP) can be seen in
      childhood and tracks into adulthood. The relationship between physical activity
      (PA) and BP in adults is well-established, but findings in children have been
      inconsistent, with few studies measuring PA mechanically. Children aged 11 to 12
      years were recruited from the Avon Longitudinal Study of Parents and Children.
      5505 had systolic and diastolic BP measurements, plus valid (at least 10 hours
      for at least 3 days) accelerometer measures of PA; total PA recorded as average
      counts per minute (cpm) over the period of valid recording, and minutes per day
      spent in moderate to vigorous PA (MVPA). Data on a number of possible confounders
      were also available. Small inverse associations were observed; for systolic BP,
      beta=-0.44 (95% confidence interval -0.59, -0.28) mm Hg per 100 cpm, and beta=
      0.66 (95% CI -0.92, -0.39) mm Hg per 15 minutes/d MVPA, adjusting for child's age
      and gender. After adjustment for potential confounders, associations were
      weakened but remained. When PA variables were modeled together, associations with
      total PA were only a little weaker, whereas those with MVPA were substantially
      reduced; for systolic BP, beta=-0.42 (95% CI -0.71, -0.13) mm Hg per 100 cpm, and
      beta=-0.03 (95% CI -0.54, 0.48) mm Hg per 15 minutes/d MVPA. In conclusion,
      higher levels of PA were associated with lower BP, and results suggested that the
      volume of activity may be more important than the intensity.

PMID- 18071056
TI  - Ethnic and genetic determinants of cardiovascular response to the selective alpha
      2-adrenoceptor agonist dexmedetomidine.
AB  - The alpha(2)-adrenoceptor agonist clonidine reduces blood pressure more
      effectively in White than Black Americans despite similar degrees of
      sympatholysis. Functional genetic variation in receptor signaling mechanisms, for
      example in the beta 3 G-protein subunit (GNB3 C825T) and in the alpha(2C)
      adrenoceptor subtype (ADRA2C del322-325), may affect drug responses. We examined
      the hypothesis that there are ethnic differences in the responses to the highly
      selective alpha(2)-agonist, dexmedetomidine, and that these genetic variants
      contribute to interindividual variability in drug responses. In a placebo
      controlled, single-masked study, 73 healthy subjects (37 whites and 36 blacks)
      received 3 placebo infusions and then 3 incremental doses of dexmedetomidine
      (cumulative dose, 0.4 microg/kg), each separated by 30 minutes. Blood pressure,
      heart rate, and plasma catecholamine concentrations were determined after each
      infusion. We measured dexmedetomidine concentrations after the last infusion and
      determined ADRA2C del322-325 and GNB3 C825T genotypes. Dexmedetomidine lowered
      blood pressure and plasma catecholamine concentrations significantly (all
      P<0.001). There was substantial interindividual variability in the reduction of
      systolic blood pressure (range, 1 to 34 mm Hg) and plasma norepinephrine
      concentrations (range, 24 to 424 pg/mL). However, there were no differences
      between black and white subjects in dexmedetomidine responses (P>0.16 for all
      outcomes) before or after adjustment for covariates. Neither ADRA2C del322-325
      nor GNB3 C825T genotypes affected the responses to dexmedetomidine (all P>0.66).
      There is large interindividual variability in response to the selective alpha(2)
      AR agonist dexmedetomidine, and neither ethnicity nor ADRA2C and GNB3 genotypes
      contribute to it. Further studies to identify determinants of alpha(2)-AR
      mediated responses will be of interest.

PMID- 18071057
TI  - Creatine kinase and the correlates of blood pressure in a random population
      sample.

PMID- 18071058
TI  - Oxidative stress, nitric oxide synthase, and superoxide dismutase: a matter of
      imbalance underlies endothelial dysfunction in the human coronary circulation.

PMID- 18071059
TI  - Nocturnal blood pressure versus nondipping pattern: what do they mean?

PMID- 18071060
TI  - Pathogenesis of elevated peripheral pulse pressure: some reflections and thinking
      forward.

PMID- 18071061
TI  - Identification of mutated Srebf1 as a QTL influencing risk for hepatic steatosis
      in the spontaneously hypertensive rat.
AB  - Approximately 30% of patients with hypertension have hepatic steatosis, and it
      has recently been proposed that fatty liver be considered a feature of the
      metabolic syndrome. Obesity, diet, and level of physical activity are likely
      factors modulating risk for hepatic steatosis, however genetic factors could also
      influence susceptibility or resistance to fatty liver in hypertensive or
      normotensive subjects. In genetic studies in spontaneously hypertensive rats
      (SHRs) and Brown Norway (BN) rats, we discovered that a variant form of sterol
      regulatory element binding transcription factor 1 (Srebf1 gene, SREBP-1 protein)
      underlies a quantitative trait locus (QTL) influencing hepatic cholesterol levels
      in response to a high cholesterol diet. Compared with the BN allele of Srebf1,
      the SHR allele of Srebf1 includes variants in the promoter and coding regions
      that are linked to hepatic deficiency of SREBP-1 mRNA and protein, reduced
      expression of the SREBP-1 target gene stearoyl-CoA desaturase 1, reduced promoter
      activity for SREBP-1c, and relative protection from dietary induced accumulation
      of liver cholesterol. Genetic correction of reduced SREBP-1 activity by
      derivation of congenic and transgenic strains of SHR increased hepatic
      cholesterol levels, thereby confirming Srebf1 as a QTL influencing hepatic lipid
      metabolism in the rat. The Srebf1 variant regulating hepatic cholesterol did not
      appear to affect blood pressure. These findings (1) are consistent with the
      results of association studies indicating that common polymorphisms affecting
      SREBP-1 may influence cholesterol synthesis in humans and (2) indicate that
      variation in Srebf1 may influence risk for hepatic steatosis.

PMID- 18071062
TI  - Brain microbleeds are associated with ambulatory blood pressure levels in a
      hypertensive population.
AB  - Brain microbleeds, indicative of cerebral small-vessel disease, may occur with
      increased frequency in patients with hypertension. However, little is known about
      the relation of these abnormalities with blood pressure levels. We assessed the
      relation between ambulatory measured blood pressure and the presence of
      microbleeds in a cohort of hypertensive patients without a history of
      cerebrovascular disease. A total of 218 participants (110 males, age 52.5+/-12.6
      years) underwent 24-hour ambulatory blood pressure monitoring twice (off
      medication) and brain MRI to detect microbleeds and coexisting white matter
      hyperintensities. We performed logistic regression analyses to relate the
      following blood pressure components (based on both recordings) to microbleeds:
      the mean 24-hour, awake, and asleep blood pressures; nocturnal hypertension
      (asleep pressure >or=120/70 mm Hg); nocturnal blood pressure dipping. Models were
      adjusted for age and sex, and additionally for cardiovascular risk factors and
      white matter hyperintensities. We detected microbleeds in 35 participants (16.1%;
      95% confidence interval, 11.1% to 21.0%). On average, each standard deviation
      increment in blood pressure, whether 24-hour, awake, or asleep, was significantly
      and independently associated with a 1.8- to 1.9-fold higher likelihood for
      microbleeds (all models P<0.05). Similarly, the adjusted odds ratio for
      microbleeds was 5- to 6-fold higher in subjects diagnosed with nocturnal
      hypertension (all models P<0.05). Microbleeds were not associated with nocturnal
      dipping. In conclusion, brain microbleeds are frequently found in hypertensive
      patients without a history of cerebrovascular disease, and are independently
      associated with higher daytime as well as night-time blood pressure levels.

PMID- 18071063
TI  - Time courses of growth and remodeling of porcine aortic media during
      hypertension: a quantitative immunohistochemical examination.
AB  - Arteries undergo marked structural and functional changes in human and
      experimental hypertension that generally involve smooth muscle cell (SMC)
      hypertrophy/hyperplasia as well as abnormal extracellular matrix turnover. In
      this study we examined time courses of changes in SMC activity and matrix protein
      content in a novel mini-pig aortic coarctation model. Cell proliferation was
      evaluated by immunostaining of Ki-67, apoptosis was assessed by TUNEL, and
      phenotypic changes were monitored by immunostaining three SMC contractile markers
      (caldesmon, calponin, and smoothelin). Changes in medial collagen and elastin
      were examined by picrosirius red and Verhoeff-van Gieson staining, respectively.
      LabVIEW-based image analysis routines were developed to objectively and
      efficiently quantify the (immuno)histochemical results. We found that significant
      cell proliferation and matrix production occurred in the early stages of this
      coarctation model and then declined gradually; the SMCs also tended to exhibit a
      less contractile phenotype following these cellular and extracellular changes.
      Specifically, different aspects of the phenotypic changes associated with
      hypertension occurred at different rates: cell proliferation and collagen
      production occurred early and peaked by 2 weeks, whereas changes in contractile
      protein expression continued to decrease over the entire 8-week study period.
      Temporal changes found in this study emphasize the importance of simultaneously
      tracing time courses of SMC growth and differentiation as well as matrix protein
      production and content. SMCs are multifunctional, and caution must be used to not
      overdefine phenotype. This manuscript contains online supplemental material at
      http://www.jhc.org. Please visit this article online to view these materials.

PMID- 18071064
TI  - Raman nanoparticle probes for antibody-based protein detection in tissues.
AB  - Surface-enhanced Raman scattering (SERS) nanoparticles are emerging as a new
      approach for optical detection of biomolecules. In a model assay in formalin
      fixed paraffin-embedded (FFPE) prostate tissue sections, we detect prostate
      specific antigen (PSA) using antibody (Ab) conjugated to composite organic
      inorganic nanoparticles (COINs), and we use identical staining protocols to
      compare COIN-Ab and Alexa-Ab conjugates in adjacent tissue sections. Spectral
      analysis illustrates the fundamental difference between fluorescence and Raman
      signatures and accurately extracts COIN probe signals from background
      autofluorescence. Probe signals are used to generate images of PSA expression on
      the tissue, and quality measures are presented to characterize the performance of
      the COIN assay in comparison to Alexa. Staining accuracy (ability to correctly
      identify PSA expression in epithelial cells) is somewhat less for COIN than
      Alexa, which is attributed to an elevated false negative rate of the COIN.
      However, COIN provided signal intensities comparable to Alexa, and good intra-,
      inter-, and lot-to-lot consistencies. Overall, COIN and Alexa detection reagents
      possess similar performance with FFPE tissues, supporting the further development
      of Raman probes for this application. This manuscript contains online
      supplemental material at http://www.jhc.org. Please visit this article online to
      view these materials.

PMID- 18071065
TI  - An immunohistochemical method for identifying fibroblasts in formalin-fixed,
      paraffin-embedded tissue.
AB  - Fibroblasts are critical for tissue homeostasis, and their inappropriate
      proliferation and activation can result in common and debilitating conditions
      including fibrosis and cancer. We currently have a poor understanding of the
      mechanisms that control the growth and activation of fibroblasts in vivo, in part
      because of a lack of suitable fibroblast markers. We have taken advantage of an
      antibody previously shown to stain stromal cells in frozen tissues (TE-7) and
      identified conditions in which it can be used to stain fibroblasts and
      myofibroblasts in the paraffin-embedded tissue samples routinely collected for
      pathological analysis. We show that this antibody recognizes growing and
      quiescent fibroblasts and myofibroblasts by immunohistochemistry,
      immunofluorescence, and ELISA assays. We also present its staining patterns in
      normal tissue samples and in breast tumors.

PMID- 18071066
TI  - p53 Nuclear accumulation and Bcl-2 expression in contiguous adenomatous
      components of colorectal adenocarcinomas predict aggressive tumor behavior.
AB  - For subsets of colorectal adenocarcinoma (CRC) patients, nuclear accumulation of
      p53 (p53(nac)) and Bcl-2 expression are prognostic indicators. To understand
      their role in the progression of CRC we evaluated 90 CRCs and their contiguous
      adenomatous components (CAdCs) for immunohistochemical expression of these
      markers. In general, p53(nac) and Bcl-2 expression was significantly increased
      when comparing normal colonic epithelia to CAdCs and CRCs. Thirteen (14%) CAdCs
      that demonstrated p53(nac) continued to express p53(nac) in their contiguous
      CRCs. A similar trend was observed in Bcl-2 expression in that the majority of
      CAdCs expressing Bcl-2 continued to express it in their matching CRCs (39/44).
      Patients whose CAdCs and their contiguous CRCs demonstrate p53(nac) had shorter
      median survival (35.9 months) than those patients whose CAdCs and CRCs did not
      (80.56 months). However, patients whose CAdCs had p53(nac) and lacked Bcl-2
      expression had the lowest median survival (15.74 months) when compared with
      patients whose CAdCs did not demonstrate p53(nac) but had increased expression of
      Bcl-2 (71.77 months). These findings suggest that in those adenomas that
      demonstrate p53(nac) but lack Bcl-2 expression, their contiguous CRCs are more
      likely to be aggressive as they progress.

PMID- 18071067
TI  - Preparation of polyclonal antibody specific for BRD7 and detection of its
      expression pattern in the human fetus.
AB  - BRD7 is a novel bromodomain gene. It plays critical role in cell growth, cell
      cycle progression, and signal-dependent gene expression. Overexpression of the
      BRD7 gene in nasopharyngeal carcinoma cells is effective to inhibit cell growth
      and cell cycle progression from G1 to S phase. However, little is known about its
      bio-functions because of the unavailability of a specific BRD7 antibody. In this
      study, for the first time, we generated a highly specific BRD7 antibody. It is
      able to specifically recognize recombinant GST-BRD7N protein with a molecular
      mass of 65 kDa and recognize BRD7-Myc and endogenously expressed BRD7 protein
      with an approximate molecular mass of 75 kDa, which corresponds well with the
      calculated molecular mass of the BRD7 protein. More importantly, with these
      antisera, we analyzed BRD7 distribution in the human fetus by Western blot and
      immunohistochemistry assays. Obvious nuclear expression of BRD7 protein presents
      in human cerebellum, pancreas, intestines, liver, and kidney. Cardiomyocyte shows
      high cytoplasm expression of the BRD7 protein. Weak nuclear expression of the
      BRD7 protein is found in human cerebrum, lung, and stomach. These data may help
      to further study the cellular role of the BRD7 gene. In particular, the prepared
      BRD7 antibody will be helpful for studying the bio-functions of endogenously
      expressed BRD7 protein.

PMID- 18071068
TI  - Long-term survival, modes of death, and predictors of mortality in patients with
      Fontan surgery.
AB  - BACKGROUND: To better define determinants of mortality in patients with
      univentricular physiology, a database registry was created of patients born in
      1985 or earlier with Fontan surgery who were followed up at Children's Hospital
      Boston. METHODS AND RESULTS: A total of 261 patients, 121 of whom (46.4%) were
      women, had a first Fontan surgery at a median age of 7.9 years: right atrium-to
      pulmonary artery connection in 135 (51.7%); right atrium to right ventricle in 25
      (9.6%); and total cavopulmonary connection in 101 (38.7%). Over a median of 12.2
      years, 76 (29.1%) died, 5 (1.9%) had cardiac transplantation, 5 (1.9%) had Fontan
      revision, and 21 (8.0%) had Fontan conversion. Perioperative mortality decreased
      steadily over time and accounted for 68.4% of all deaths. In early survivors,
      actuarial freedom from death or transplantation was 93.7%, 89.9%, 87.3%, and
      82.6% at 5, 10, 15, and 20 years, respectively, with no significant difference
      between right atrium to pulmonary artery versus total cavopulmonary connection.
      Late deaths were classified as sudden in 7 patients (9.2%), thromboembolic in 6
      (7.9%), heart failure-related in 5 (6.7%), sepsis in 2 (2.6%), and other in 4
      (5.2%). Most sudden deaths were of presumed arrhythmic origin with no
      identifiable predictor. Independent risk factors for thromboembolic death were
      lack of antiplatelet or anticoagulant therapy (hazard ratio [HR], 91.6; P=0.0041)
      and clinically diagnosed intracardiac thrombus (HR, 22.7; P=0.0002). Independent
      predictors of heart failure death were protein-losing enteropathy (HR, 7.1;
      P=0.0043), single morphologically right ventricle (HR, 10.5; P=0.0429), and
      higher right atrial pressure (HR, 1.3 per 1 mm Hg; P=0.0016). CONCLUSIONS: In
      perioperative survivors of Fontan surgery, gradual attrition occurs predominantly
      from thromboembolic, heart failure-related, and sudden deaths.

PMID- 18071069
TI  - Cardiac sodium channel gene variants and sudden cardiac death in women.
AB  - BACKGROUND: Several cardiac ion channel genes have been implicated in monogenic
      traits with a high risk of sudden cardiac death (SCD). Mutations or rare variants
      in these genes have been proposed as potential contributors to more common forms
      of SCD, but this hypothesis has not been assessed systematically. METHODS AND
      RESULTS: We directly sequenced the entire coding region and splice junctions of 5
      cardiac ion channel genes, SCN5A, KCNQ1, KCNH2, KCNE1, and KCNE2, in 113 SCD
      cases from 2 large prospective cohorts of women (Nurses' Health Study) and men
      (Health Professional Follow-Up Study). Controls from the same population were
      then screened for the presence of mutations or rare variants identified in cases,
      and sequence variants without prior functional data were expressed in Xenopus
      oocytes to assess their biophysical consequences. No mutations or rare variants
      were identified in any of the 53 subjects who were men. In contrast, in 6 of 60
      women (10%), we identified 5 rare missense variants in SCN5A that either had been
      associated previously with long-QT syndrome (A572D and G615E), had been reported
      to alter sodium channel function (F2004L), or had not been reported previously in
      control populations (A572F and W1205C). Of the 4 variants without prior
      functional data, 3 variants were located in the I-II linker (A572D, A572F, and
      G615E), and all resulted in significantly shorter recovery times from
      inactivation. When compared with 733 control samples from the same population,
      the overall frequency of these rare variants in SCN5A was significantly higher in
      the SCD cases (6/60, 10.0%) than in controls (12/733, 1.6%; P=0.001).
      CONCLUSIONS: Functionally significant mutations and rare variants in SCN5A may
      contribute to SCD risk among women.

PMID- 18071070
TI  - Adenylyl cyclase type 6 deletion decreases left ventricular function via impaired
      calcium handling.
AB  - BACKGROUND: Adenylyl cyclases (ACs) are a family of effector molecules for G
      protein-coupled receptors. The 2 ACs most abundantly expressed in cardiac
      myocytes are types 5 (AC5) and 6 (AC6), which have 65% amino acid homology. It
      has been speculated that coexpression of 2 AC types in cardiac myocytes
      represents redundancy, but the specific role of AC6 in cardiac physiology and its
      differences from AC5 remain to be defined. METHODS AND RESULTS: We generated
      transgenic mice with targeted deletion of AC6. Deletion of AC6 was associated
      with reduced left ventricular contractile function (P=0.026) and relaxation
      (P=0.041). The absence of AC6 was associated with a 48% decay in beta-adrenergic
      receptor-stimulated cAMP production in cardiac myocytes (P=0.003) and reduced
      protein kinase A activity (P=0.015). In addition, phospholamban phosphorylation
      was reduced (P=0.015), sarcoplasmic reticulum Ca2+-ATPase activity was impaired
      (P<0.0001), and cardiac myocytes showed marked abnormalities in calcium transient
      formation (P=0.001). CONCLUSIONS: The combination of impaired cardiac cAMP
      generation and calcium handling that result from AC6 deletion underlies
      abnormalities in left ventricular function. The biochemical and physiological
      consequences of AC6 deletion reveal it to be an important effector molecule in
      the adult heart, serving unique biological functions not replicated by AC5.

PMID- 18071071
TI  - Diastolic stiffness of the failing diabetic heart: importance of fibrosis,
      advanced glycation end products, and myocyte resting tension.
AB  - BACKGROUND: Excessive diastolic left ventricular stiffness is an important
      contributor to heart failure in patients with diabetes mellitus. Diabetes is
      presumed to increase stiffness through myocardial deposition of collagen and
      advanced glycation end products (AGEs). Cardiomyocyte resting tension also
      elevates stiffness, especially in heart failure with normal left ventricular
      ejection fraction (LVEF). The contribution to diastolic stiffness of fibrosis,
      AGEs, and cardiomyocyte resting tension was assessed in diabetic heart failure
      patients with normal or reduced LVEF. METHODS AND RESULTS: Left ventricular
      endomyocardial biopsy samples were procured in 28 patients with normal LVEF and
      36 patients with reduced LVEF, all without coronary artery disease. Sixteen
      patients with normal LVEF and 10 with reduced LVEF had diabetes mellitus. Biopsy
      samples were used for quantification of collagen and AGEs and for isolation of
      cardiomyocytes to measure resting tension. Diabetic heart failure patients had
      higher diastolic left ventricular stiffness irrespective of LVEF. Diabetes
      mellitus increased the myocardial collagen volume fraction only in patients with
      reduced LVEF (from 14.6+/-1.0% to 22.4+/-2.2%, P<0.001) and increased
      cardiomyocyte resting tension only in patients with normal LVEF (from 5.1+/-0.7
      to 8.5+/-0.9 kN/m2, P=0.006). Diabetes increased myocardial AGE deposition in
      patients with reduced LVEF (from 8.8+/-2.5 to 24.1+/-3.8 score/mm2; P=0.005) and
      less so in patients with normal LVEF (from 8.2+/-2.5 to 15.7+/-2.7 score/mm2,
      P=NS). CONCLUSIONS: Mechanisms responsible for the increased diastolic stiffness
      of the diabetic heart differ in heart failure with reduced and normal LVEF:
      Fibrosis and AGEs are more important when LVEF is reduced, whereas cardiomyocyte
      resting tension is more important when LVEF is normal.

PMID- 18071072
TI  - Effectiveness of bystander-initiated cardiac-only resuscitation for patients with
      out-of-hospital cardiac arrest.
AB  - BACKGROUND: Previous animal and clinical studies suggest that bystander-initiated
      cardiac-only resuscitation may be superior to conventional cardiopulmonary
      resuscitation (CPR) for out-of-hospital cardiac arrests. Our hypothesis was that
      both cardiac-only bystander resuscitation and conventional bystander CPR would
      improve outcomes from out-of-hospital cardiac arrests of < or = 15 minutes'
      duration, whereas the addition of rescue breathing would improve outcomes for
      cardiac arrests lasting > 15 minutes. METHODS AND RESULTS: We carried out a
      prospective, population-based, observational study involving consecutive patients
      with emergency responder resuscitation attempts from May 1, 1998, through April
      30, 2003. The primary outcome measure was 1-year survival with favorable
      neurological outcome. Multivariable logistic regression analysis was performed to
      evaluate the relationship between type of CPR and outcomes. Among the 4902
      witnessed cardiac arrests, 783 received conventional CPR, and 544 received
      cardiac-only resuscitation. Excluding very-long-duration cardiac arrests (> 15
      minutes), the cardiac-only resuscitation yielded a higher rate of 1-year survival
      with favorable neurological outcome than no bystander CPR (4.3% versus 2.5%; odds
      ratio, 1.72; 95% CI, 1.01 to 2.95), and conventional CPR showed similar
      effectiveness (4.1%; odds ratio, 1.57; 95% CI, 0.95 to 2.60). For the very-long
      duration arrests, neurologically favorable 1-year survival was greater in the
      conventional CPR group, but there were few survivors regardless of the type of
      bystander CPR (0.3% [2 of 624], 0% [0 of 92], and 2.2% [3 of 139] in the no
      bystander CPR, cardiac-only CPR, and conventional CPR groups, respectively;
      P<0.05). CONCLUSIONS: Bystander-initiated cardiac-only resuscitation and
      conventional CPR are similarly effective for most adult out-of-hospital cardiac
      arrests. For very prolonged cardiac arrests, the addition of rescue breathing may
      be of some help.

PMID- 18071073
TI  - Platelet sarcoplasmic endoplasmic reticulum Ca2+-ATPase and mu-calpain activity
      are altered in type 2 diabetes mellitus and restored by rosiglitazone.
AB  - BACKGROUND: Platelets from patients with type 2 diabetes mellitus display
      hyperaggregability and increased thrombogenic potential. METHODS AND RESULTS: In
      platelets from patients with type 2 diabetes mellitus, we found enhanced tyrosine
      nitration and inactivation of the sarcoplasmic endoplasmic reticulum Ca2+-ATPase
      (SERCA-2), elevated platelet [Ca2+]i, and activation of mu-calpain. The tyrosine
      nitration of SERCA-2 and the activation of mu-calpain in vitro in platelets from
      healthy volunteers could be evoked in vitro by peroxynitrite. Platelet
      endothelial cell adhesion molecule-1 was identified as a mu-calpain substrate;
      its in vitro degradation was stimulated by peroxynitrite and prevented by calpain
      inhibitors. Calpain activation also was linked to hyperresponsiveness to thrombin
      and the loss of platelet sensitivity to nitric oxide synthase inhibitors.
      Platelets from patients with type 2 diabetes mellitus (hemoglobin A1c >6.6%)
      contained little or no intact platelet endothelial cell adhesion molecule-1,
      whereas degradation products were detectable. The peroxisome proliferator
      activated receptor-gamma agonist rosiglitazone increased SERCA-2 expression in
      megakaryocytes, and treating patients with type 2 diabetes mellitus with
      rosiglitazone for 12 weeks increased platelet SERCA-2 expression and Ca2+-ATPase
      activity, decreased SERCA-2 tyrosine nitration, and normalized platelet [Ca2+]i.
      Rosiglitazone also reduced mu-calpain activity, normalized platelet endothelial
      cell adhesion molecule-1 levels, and partially restored platelet sensitivity to
      nitric oxide synthase inhibition. CONCLUSIONS: These data identify
      megakaryocytes/platelets as additional cellular targets for peroxisome
      proliferator-activated receptor-gamma agonists and highlight potential benefits
      of rosiglitazone therapy in cardiovascular diseases.

PMID- 18071074
TI  - Utility of currently recommended pediatric dyslipidemia classifications in
      predicting dyslipidemia in adulthood: evidence from the Childhood Determinants of
      Adult Health (CDAH) study, Cardiovascular Risk in Young Finns Study, and Bogalusa
      Heart Study.
AB  - BACKGROUND: New age- and sex-specific lipoprotein cut points developed from
      National Health and Nutrition Examination Survey (NHANES) data are considered to
      be a more accurate classification of a high-risk lipoprotein level in adolescents
      compared with existing cut points established by the National Cholesterol
      Education Program (NCEP). The aim of this study was to determine which of the
      NHANES or NCEP adolescent lipoprotein classifications was most effective for
      predicting abnormal levels in adulthood. METHODS AND RESULTS: Adolescent and
      adult measures of total cholesterol, low-density lipoprotein cholesterol, high
      density lipoprotein cholesterol, and triglycerides were collected in 365
      Australian, 1185 Finnish, and 273 US subjects participating in 3 population-based
      prospective cohort studies. Lipoprotein variables in adolescence were classified
      according to NCEP and NHANES cut points and compared for their ability to predict
      abnormal levels in adulthood. With the use of diagnostic performance statistics
      (sensitivity, specificity, positive predictive value, negative predictive value,
      area under receiver operating characteristic curve) in pooled and cohort
      stratified data, the NHANES cut points (compared with NCEP cut points) were more
      strongly predictive of low high-density lipoprotein cholesterol in adults but
      less predictive of high total cholesterol, high low-density lipoprotein
      cholesterol, and high triglyceride levels in adults. We identified heterogeneity
      in the relative usefulness of each classification between cohorts. CONCLUSIONS:
      The separate use of NHANES cut points for high-density lipoprotein cholesterol
      and NCEP cut points for total cholesterol, low-density lipoprotein cholesterol,
      and triglycerides yielded the most accurate classification of adolescents who
      developed dyslipidemia in adulthood.

PMID- 18071075
TI  - C1-esterase inhibitor protects against neointima formation after arterial injury
      in atherosclerosis-prone mice.
AB  - BACKGROUND: Although activation of the complement system has been implicated in
      the progression of human atherosclerosis, its function during arterial remodeling
      after injury has not been investigated. Here, we examined the contribution of the
      complement cascade to neointima formation in apolipoprotein E-deficient mice
      using a C1-esterase inhibitor (C1-inhibitor). METHODS AND RESULTS: Apolipoprotein
      E-deficient mice fed an atherogenic diet were subjected to wire-induced
      endothelial denudation of the carotid artery and treated with C1-inhibitor
      (Berinert; 15 IU i.v.) or vehicle perioperatively and subsequently every 2 days.
      The effectiveness of C1-inhibitor treatment was confirmed by measurement of
      plasma C1-inhibitor activity. A significant reduction in serum triglyceride
      levels was observed in C1-inhibitor-treated mice, whereas cholesterol levels did
      not differ. After 3 weeks, neointimal area was significantly reduced in C1
      inhibitor-treated mice versus controls, whereas medial area was unaltered. This
      was associated with a significant decrease in neointimal and medial macrophage
      and CD3+ T-cell content. Expression of C3 mRNA was significantly reduced in
      plaques of C1-inhibitor-treated mice 10 days after injury, as assessed by reverse
      transcription polymerase chain reaction. The peak in serum C3 levels after injury
      was markedly downregulated by C1-inhibitor, as evidenced by ELISA.
      Immunohistochemistry revealed strong expression of C3 and C3c, which colocalized
      to plaque macrophages and was reduced in C1-inhibitor-treated mice. C1-inhibitor
      impaired monocyte arrest on activated endothelium and platelets under flow
      conditions in vitro and leukocyte recruitment to carotid arteries 1 day after
      injury in vivo. CONCLUSIONS: C1-inhibitor limits neointimal plaque formation and
      inflammation. This may involve blockade of complement activation, inhibition of
      leukocyte recruitment, and reduced triglyceride levels, thus providing a
      multimodal approach to treat arterial disease.

PMID- 18071076
TI  - Which hospitals have significantly better or worse than expected mortality rates
      for acute myocardial infarction patients? Improved risk adjustment with present
      at-admission diagnoses.
AB  - BACKGROUND: Public reports that compare hospital mortality rates for patients
      with acute myocardial infarction are commonly used strategies for improving the
      quality of care delivered to these patients. Fair comparisons of hospital
      mortality rates require thorough adjustments for differences among patients in
      baseline mortality risk. This study examines the effect on hospital mortality
      rate comparisons of improved risk adjustment methods using diagnoses reported as
      present-at-admission. METHODS AND RESULTS: Logistic regression models and related
      methods originally used by California to compare hospital mortality rates for
      patients with acute myocardial infarction are replicated. These results are
      contrasted with results obtained for the same hospitals by patient-level
      mortality risk adjustment models using present-at-admission diagnoses, using 3
      statistical methods of identifying hospitals with higher or lower than expected
      mortality: indirect standardization, adjusted odds ratios, and hierarchical
      models. Models using present-at-admission diagnoses identified substantially
      fewer hospitals as outliers than did California model A for each of the 3
      statistical methods considered. CONCLUSIONS: Large improvements in statistical
      performance can be achieved with the use of present-at-admission diagnoses to
      characterize baseline mortality risk. These improvements are important because
      models with better statistical performance identify different hospitals as having
      better or worse than expected mortality.

PMID- 18071077
TI  - Survival is similar after standard treatment and chest compression only in out-of
      hospital bystander cardiopulmonary resuscitation.
AB  - BACKGROUND: We sought to compare the 1-month survival rates among patients after
      out-of-hospital cardiac arrest who had been given bystander cardiopulmonary
      resuscitation (CPR) in relation to whether they had received standard CPR with
      chest compression plus mouth-to-mouth ventilation or chest compression only.
      METHODS AND RESULTS: All patients with out-of-hospital cardiac arrest who
      received bystander CPR and who were reported to the Swedish Cardiac Arrest
      Register between 1990 and 2005 were included. Crew-witnessed cases were excluded.
      Among 11,275 patients, 73% (n=8209) received standard CPR, and 10% (n=1145)
      received chest compression only. There was no significant difference in 1-month
      survival between patients who received standard CPR (1-month survival=7.2%) and
      those who received chest compression only (1-month survival=6.7%). CONCLUSIONS:
      Among patients with out-of-hospital cardiac arrest who received bystander CPR,
      there was no significant difference in 1-month survival between a standard CPR
      program with chest compression plus mouth-to-mouth ventilation and a simplified
      version of CPR with chest compression only.

PMID- 18071078
TI  - 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients
      With ST-Elevation Myocardial Infarction: a report of the American College of
      Cardiology/American Heart Association Task Force on Practice Guidelines:
      developed in collaboration With the Canadian Cardiovascular Society endorsed by
      the American Academy of Family Physicians: 2007 Writing Group to Review New
      Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients
      With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing
      Committee.

PMID- 18071079
TI  - Effects of angiotensin-converting enzyme inhibition in low-risk patients early
      after coronary artery bypass surgery.
AB  - BACKGROUND: Early after coronary artery bypass surgery (CABG), activation of
      numerous neurohumoral and endogenous vasodilator systems occurs that could be
      influenced favorably by angiotensin-converting enzyme inhibitors. METHODS AND
      RESULTS: The Ischemia Management with Accupril post-bypass Graft via Inhibition
      of the coNverting Enzyme (IMAGINE) trial tested whether early initiation (< or =
      7 days) of an angiotensin-converting enzyme inhibitor after CABG reduced
      cardiovascular events in stable patients with left ventricular ejection fraction
      > or = 40%. The trial was a double-blind, placebo-controlled study of 2553
      patients randomly assigned to quinapril, target dose 40 mg/d, or placebo, who
      were followed up to a maximum of 43 months. The mean (SD) age was 61 (10) years.
      The incidence of the primary composite end point (cardiovascular death,
      resuscitated cardiac arrest, nonfatal myocardial infarction, coronary
      revascularization, unstable angina or heart failure requiring hospitalization,
      documented angina, and stroke) was 13.7% in the quinapril group and 12.2% in the
      placebo group (hazard ratio 1.15, 95% confidence interval 0.92 to 1.42, P=0.212)
      over a median follow-up of 2.95 years. The incidence of the primary composite end
      point increased significantly in the first 3 months after CABG in the quinapril
      group (hazard ratio 1.52, 95% confidence interval 1.03 to 2.26, P=0.0356).
      Adverse events also increased in the quinapril group, particularly during the
      first 3 months after CABG. CONCLUSIONS: In patients at low risk of cardiovascular
      events after CABG, routine early initiation of angiotensin-converting enzyme
      inhibitor therapy does not appear to improve clinical outcome up to 3 years after
      CABG; however, it increases the incidence of adverse events, particularly early
      after CABG. Thus, early after CABG, initiation of angiotensin-converting enzyme
      inhibitor therapy should be individualized and continually reassessed over time
      according to risk.

PMID- 18071080
TI  - Body fat distribution and risk of coronary heart disease in men and women in the
      European Prospective Investigation Into Cancer and Nutrition in Norfolk cohort: a
      population-based prospective study.
AB  - BACKGROUND: Body fat distribution has been cross-sectionally associated with
      atherosclerotic disease risk factors, but the prospective relation with coronary
      heart disease remains uncertain. METHODS AND RESULTS: We examined the prospective
      relation between fat distribution indices and coronary heart disease among 24,508
      men and women 45 to 79 years of age using proportional hazards regression. During
      a mean 9.1 years of follow-up, 1708 men and 892 women developed coronary heart
      disease. The risk for developing subsequent coronary heart disease increased
      continuously across the range of waist-hip ratio. Hazard ratios (95% CI) of the
      top versus bottom fifth of waist-hip ratio were 1.55 (1.28 to 1.73) in men and
      1.91 (1.44 to 2.54) in women after adjustment for body mass index and other
      coronary heart disease risk factors. Hazard ratios increased with waist
      circumference, but risk estimates for waist circumference without hip
      circumference adjustment were lower by 10% to 18%. After adjustment for waist
      circumference, body mass index, and coronary heart disease risk factors, hazard
      ratios for 1-SD increase in hip circumference were 0.80 (95% CI, 0.74 to 0.87) in
      men and 0.80 (95% CI, 0.69 to 0.93) in women. Hazard ratios for body mass index
      were greatly attenuated when we adjusted for waist-hip ratio or waist
      circumference and other covariates. CONCLUSIONS: Indices of abdominal obesity
      were more consistently and strongly predictive of coronary heart disease than
      body mass index. These simple and inexpensive measurements could be used to
      assess obesity-related coronary heart disease risk in relatively healthy men and
      women.

PMID- 18071081
TI  - Music and the heart. Interview by Emma Baines.

PMID- 18071082
TI  - Images in cardiovascular medicine. Leiomyosarcoma involving main and left
      pulmonary artery treated surgically with homograft replacement and concomitant
      left pneumonectomy.

PMID- 18071083
TI  - Letter by Tartiere et al regarding article, "Cardiac structure and ventricular
      vascular function in persons with heart failure and preserved ejection fraction
      from Olmsted County, Minnesota".

PMID- 18071084
TI  - Letter by Herring and Paterson regarding article, "Common NOS1AP variants are
      associated with a prolonged QTc interval in the Rotterdam Study".

PMID- 18071085
TI  - Atrial fibrillation-atrial flutter interactions: clinical implications for
      ablation.

PMID- 18071086
TI  - Bleeding is bad.... isn't it?

PMID- 18071087
TI  - The ischemic heart: starving to stimulate the adiponectin-AMPK signaling axis.

PMID- 18071088
TI  - Inflammation ushers in calcification: a cycle of damage and protection?

PMID- 18071089
TI  - Carcinoid heart disease.

PMID- 18071090
TI  - Prospects for percutaneous valve therapies.

PMID- 18071091
TI  - Antiemetics, akathisia, and pregnancy.
AB  - Gastrointestinal disorders are common in pregnant women. These disorders are
      often treated with antiemetic medications that block central dopaminergic
      neurotransmission. Dopamine antagonists can cause akathisia. Hormonal changes and
      other factors may place pregnant women at increased risk for the development of
      severe antiemetic-induced akathisia. The mental symptoms that can accompany
      akathisia can be misinterpreted as primary mental illness. The author reports on
      the case of a pregnant woman who attempted to injure herself after developing
      severe antiemetic-induced akathisia.

PMID- 18071092
TI  - Psychosocial aspects of pulmonary hypertension: a review.
AB  - Pulmonary arterial hypertension (PAH) is characterized by progressive and
      sustained elevation of pulmonary-artery pressure, which ultimately leads to right
      ventricular failure and death. The diagnosis carries with it an uncertain and
      historically very bleak prognosis. Although new oral and chronic parenteral
      (intravenous and subcutaneous) treatments have had a significant positive medical
      impact on the physical functioning of individuals with PAH, patients often
      struggle with new short- and long-term psychosocial challenges. The purpose of
      the current article is to 1) provide a brief review of PAH and its treatment; 2)
      summarize the limited literature examining the psychosocial adjustment of those
      with a PAH diagnosis; and 3) provide pertinent information extrapolated from the
      larger literature on chronic illness that might inform us on the psychosocial
      challenges faced by the patient diagnosed with PAH.

PMID- 18071093
TI  - Parental physical illness as a risk for psychosocial maladjustment in children
      and adolescents: epidemiological findings from a national survey in Germany.
AB  - The authors assessed the risk for psychosocial maladjustment in a population
      based sample of dependent children of parents with serious physical illness. In
      the context of The Hamburg Health Survey, a wide range of data on current life
      situation and health status was collected from a representative sample of
      families with children and adolescents between 4 and 18 years old (N=1,950). For
      4- to 18-year-old children and adolescents in Germany, the prevalence of a
      serious physical illness in a parent was 4.1%. The adjusted risk of psychosocial
      maladjustment in this target group, depending on the case definition, is
      elevated, with internalizing problems being more prevalent than externalizing
      problems. Although problems for affected boys decline with puberty, they increase
      for girls. In this age-group, girls and boys appear to be under particular strain
      when the respective same-sex parent has a serious physical illness. Exposure to
      serious parental physical illness is an epidemiologically relevant risk factor
      for psychosocial maladjustment in children and adolescents that needs to be
      better recognized by medical professionals.

PMID- 18071094
TI  - Depression treatment preferences of VA primary care patients.
AB  - The authors identified veterans' depression treatment preferences and explored
      relationships between preferences, process of care, and clinical outcomes.
      Patients entering a collaborative depression intervention trial in primary care
      completed an assessment of treatment preferences. Medical record review was used
      to identify treatments offered and received over a 12-month period. Of 314
      patients, 32% preferred antidepressants; 19%, individual counseling; 18%, anti
      depressants plus counseling; 7%, group counseling; and 25%, "watchful waiting."
      Although the treatment that was offered was associated with treatment
      preferences, being offered preferred treatment was not associated with receiving
      treatment or with changes in depression severity or satisfaction over time.

PMID- 18071095
TI  - Alexithymia and emotional distress in patients with central serous
      chorioretinopathy.
AB  - The authors studied 31 consecutive patients newly diagnosed with central serous
      chorioretinopathy (CSC) as compared with 31 age- and gender-matched control
      subjects, assessing emotional distress (ED), nine psychopathological symptoms,
      critical life events, and alexithymia. Results showed no difference in the number
      of critical life events; however CSC patients showed elevated ED and elevated
      scores on seven psychopathological symptoms, including hostility. Controlling for
      ED, CSC patients showed elevated alexithymia sum scores. Alexithymia was
      correlated with hostility. Our findings point to personality-based difficulties
      in emotional regulation associated with hostility in CSC.

PMID- 18071096
TI  - Chronic obstructive lung diseases and prevalence of mood, anxiety, and substance
      use disorders in a large population sample.
AB  - Only a few population-based studies have examined prevalence of mental disorder
      in people with chronic respiratory conditions. Clinical studies have yielded
      mixed results. In this analysis, data from the 2002 Canadian Community Health
      Survey (CCHS) were used. This was a national health survey that included
      administration of the World Mental Health Composite International Diagnostic
      Interview to a sample of 36,984 subjects. Participants were asked about chronic
      medical conditions that had been diagnosed by a health professional. Chronic
      respiratory conditions were associated with major depressive disorder, bipolar
      disorder, panic disorder (including agoraphobia), social phobia, and substance
      dependence. Although the observed associations were statistically highly
      significant, the prevalence estimates were lower than previous reports from
      studies using clinical samples, suggesting that selection bias may have
      influenced some estimates.

PMID- 18071097
TI  - Course and outcome of somatoform disorders in non-referred adolescents.
AB  - The author examined the course of somatoform disorders in non-referred
      adolescents. Somatoform disorders were coded from DSM-IV criteria, using the
      computerized Munich (Germany) version of the Composite International Diagnostic
      Interview. About 35.9% of the adolescents with somatoform disorders at the index
      investigation continued to have the same disorders at the follow-up
      investigation: 26.7% had anxiety, 17.1% had depression, 22% had substance-use
      disorders, and 53.7% had no psychiatric disorders. Factors related to the
      chronicity of somatoform disorders included gender, comorbid depressive
      disorders, parental psychiatric disorders, and negative life events. Somatoform
      disorders showed a heterogeneous pattern of course.

PMID- 18071098
TI  - Comparison of participants and non-participants in a randomized psychosocial
      intervention study among patients with malignant melanoma.
AB  - The authors investigated barriers for entering a randomized psychosocial
      intervention study among patients with malignant melanoma. Data on age, sex,
      prognostic factors, social class, marital status, mood, coping, social relations,
      and social desirability from participants and non-participants were compared in a
      regression model. More patients in lower socioeconomic classes declined
      participation. Non-participation was associated with low levels of distress and
      adaptive coping and higher levels of empathy and congruence from spouses. The
      type of intervention offered in this study may have more appeal to patients
      belonging to higher socioeconomic classes.

PMID- 18071099
TI  - A comparison of psychiatric consultation liaison services between hospitals in
      the United States and Japan.
AB  - The authors investigated psychiatric consultation in two hospitals, one in the
      United States, the other in Japan. They examined similarities and differences,
      and drew inferences on possible cross-cultural values and/or temporary cultural
      conditions. As compared with the Japanese consultation patients, the Americans
      had more mood disorders, including anxiety and chemical-dependency problems, in
      respective diagnostic classifications. Patients in the United States also showed
      more acute as well as more serious chronic conditions. These differences may
      relate to disorder base-rates in the respective countries. In general,
      psychosocial problems emerged as ascendant in Japan, as compared with chemical
      dependency difficulties among American patients. The results are discussed in
      terms of current conditions in Japan that affect the mental health professions,
      together with attempts by Japanese clinicians to protect collective mores by
      ascribing causation for disorders to the individual, rather than the societal
      conditions often invoked in the United States.

PMID- 18071100
TI  - Alexithymia and life satisfaction in primary healthcare patients.
AB  - The relationship between life satisfaction and alexithymia was studied in a
      sample of 229 patients as a part of a naturalistic follow-up study of depression
      in Finnish primary health care. The measures were the abbreviated Life
      Satisfaction Scale and the 20-item Toronto Alexithymia Scale. Depression was
      assessed by telephone with the short form of the Composite International
      Diagnostic Interview. Of all subjects, 19.2% were alexithymic, and 9.2% were
      depressed. Alexithymia was negatively associated with life satisfaction even when
      depression and other confounding factors were controlled for. Alexithymia is a
      risk factor for life dissatisfaction in primary-care patients.

PMID- 18071101
TI  - Quetiapine-induced leucopenia and thrombocytopenia.
AB  - Antipsychotic drugs can cause neutropenia, which can progress to life-threatening
      agranulocytosis if drug therapy is not interrupted. The newer atypical
      antipsychotics are reputedly without adverse hematological effects. Quetiapine is
      a recently introduced atypical antipsychotic. It is a dibenzothiazepine
      derivative and shows similarities with clozapine in that it is characterized by
      high 5-HT(2)-relative-to-DA(2) receptor affinity. Although adverse effects are
      usually mild, the author reports here a case of leucocytopenia and
      thrombocytopenia with quetiapine treatment that required its discontinuation.

PMID- 18071102
TI  - Parathyroid adenoma presenting as bipolar affective disorder.

PMID- 18071103
TI  - Treatment of catatonia with olanzapine and amantadine.
AB  - Catatonia is a disorder characterized by mutism, posturing, echophenomena, and
      negativism. The preferred treatment for non-malignant catatonia is
      benzodiazepines, which often produce a reduction in symptoms within 24 hours.
      Presented here is a case report of a 19-year-old woman appearing in a catatonic
      state that did not respond to lorazepam. On the basis of emerging evidence that
      atypical antipsychotics and weak N-Methyl-D-Aspartate (NMDA) receptor-antagonists
      may effectively treat catatonia, we treated our patient with olanzapine and
      amantadine, which resulted in a dramatic reduction in her catatonic symptoms.

PMID- 18071104
TI  - Cardiovascular medications.

PMID- 18071105
TI  - Nonepileptic hallucinations in use of levetiracetam.

PMID- 18071106
TI  - Additional information on German study about denial and concealment of pregnancy.

PMID- 18071107
TI  - Techniques and outcomes of total upper and lower eyelid reconstruction.
AB  - OBJECTIVES: To describe techniques used for reconstruction of the eyelids
      following total loss of the upper and lower eyelids and to describe visual and
      functional outcomes. METHODS: Multicenter, retrospective, interventional case
      series of all of the patients requiring unilateral reconstruction of both the
      upper and lower eyelids. RESULTS: Six cases were identified, 1 following trauma
      and 5 following tumor excision (4 with basal cell carcinoma and 1 with melanoma).
      The median age was 69 years (range, 18-90 years). Primary repair using preserved
      tissue was carried out in the case of traumatic avulsion. Following tumor
      excision, bilamellar repair was performed using composite grafts for the
      posterior lamella and skin-muscle flaps for the anterior lamella. Graft necrosis
      occurred in 3 cases (50%). In all of the cases, the reconstructed eyelids were
      stiff and immobile. Lagophthalmos (6 cases [100%]), ptosis (3 cases [50%]), lower
      eyelid retraction (3 cases [50%]), and ectropion (2 cases [33%]) were common.
      Useful vision was retained in all of the cases. CONCLUSIONS: Total eyelid defects
      are rare and often unanticipated. Adequate corneal protection can be achieved
      using lamellar repair principles and local tissues; however, poor vascularity
      demands careful planning, with vascularized flaps favored over free grafts.
      Reconstructed eyelids have poor function in the setting of total upper and lower
      eyelid loss, and revision surgery is often required to improve eyelid structure
      and function.

PMID- 18071108
TI  - Effect of upper eyelid surgery on corneal topography.
AB  - OBJECTIVE: To compare the effects of different upper eyelid procedures on corneal
      topography. METHODS: Eighty-two eyes of 43 patients with various degrees of
      dermatochalasis or ptosis underwent computed corneal topography before surgery
      and at 3 months after surgery. Patients were divided into groups depending on the
      extent of surgery. In addition, the thickness of the central cornea was
      correlated with the change in astigmatism. RESULTS: There were mean changes in
      total astigmatism of 0.25 diopter (D) after ptosis surgery (P = .02) and 0.21 D
      after blepharoplasty with reduction of large fat pads (P = .04) compared with
      0.09 D in patients after skin-only blepharoplasty. In addition, there was a
      correlation between corneal thickness and change in astigmatism of more than 0.2
      cylinders after ptosis surgery (P < .05). Postoperative astigmatic axis changes
      were not systematic. CONCLUSIONS: We found a statistically significant
      correlation between the severity of upper eyelid abnormality and topographical
      corneal changes after surgery. These findings emphasize the importance of
      advising patients, especially those with ptosis and severe dermatochalasis, that
      upper eyelid repositioning procedures may induce vision changes.

PMID- 18071109
TI  - Lash ptosis in congenital and acquired blepharoptosis.
AB  - OBJECTIVE: To determine the prevalence of lash ptosis (LP) in eyes with
      congenital and acquired blepharoptosis. METHODS: We retrospectively graded
      photographs of 228 eyes from 174 patients with congenital or acquired
      blepharoptosis for LP. We used a 4-point rating scale for LP, in which 0
      indicates no LP; 1, minimal; 2, moderate; and 3, severe. A prospective evaluation
      of LP in 30 eyes from 15 patients without blepharoptosis (control eyes) was also
      performed. RESULTS: A total of 107 eyes (in 87 patients) demonstrated congenital
      blepharoptosis and 121 eyes (in 87 patients) had acquired blepharoptosis. A
      moderate to severe rating of LP (rating, >/= 2) occurred in 60.7% of eyes with
      congenital blepharoptosis, 28.9% of eyes with acquired blepharoptosis, and 6.7%
      of control eyes. Lash ptosis (rating, >/= 1) was present in 91.6% of eyes with
      congenital blepharoptosis, 83.5% of eyes with acquired blepharoptosis, and 33.3%
      of control eyes. The mean LP rating was 2.1 for eyes with congenital
      blepharoptosis, 1.3 for eyes with acquired blepharoptosis, and 0.6 for control
      eyes. CONCLUSIONS: Lash ptosis was common in the patients with blepharoptosis.
      Moderate to severe LP occurred more commonly in all forms of blepharoptosis
      compared with normal eyes, with more frequent and more severe LP demonstrated in
      eyes with congenital blepharoptosis.

PMID- 18071110
TI  - Mechanisms and treatment of extruding intraconal implants: socket aging and
      tissue restitution (the "Cactus Syndrome").
AB  - OBJECTIVE: To investigate the initial features and treatment of 26 consecutive
      patients referred with extruding orbital implants between January 1991 and
      December 2004. METHODS: Retrospective medical record review recording the reason
      for enucleation, primary implant type, infection when initially seen, time to
      implant exposure, location of conjunctival defect, and time to surgical revision.
      RESULTS: Of the 26 eyes, 16 (62%) were removed after trauma, 3 (12%) because of
      tumor, 3 (12%) because of infection, and 4 (15%) because of painful blind eyes
      (percentages do not total 100 because of rounding). Of the 26 eyes, 8 (31%) were
      right eyes and 15 (58%) were hemispheric implants; 8 implants (31%) were acrylic
      or glass spheres, and 1 (4%) each was a hydroxyapatite, porous polythene, or bone
      sphere. Hemisphere extrusion occurred at a mean of 16 years after implantation,
      significantly later than with spheres (mean, 10 years after implantation; P =
      .05). The conjunctiva was breached medially in only 1 (sphere) (4%), centrally in
      13 (50%), and laterally in 12 (46%). Lateral erosion occurred solely with
      hemispheres, in contrast to central erosions, in which 10 of 13 (77%) were
      spheres (P < .001). Twelve patients (46%) underwent surgical revision within a
      year of extrusion, 7 (27%) within 2 years, and the remaining 7 (27%) at 2 to 21
      years. CONCLUSIONS: Exposure of hemispheres occurred later, from pressure erosion
      at their prominent lateral edge. In contrast, central erosion (in spheres)
      occurred earlier, because of gradual tissue restitution after forced-ball
      implantation ("cactus syndrome"). This may be avoided by implantation through a
      polythene glide.

PMID- 18071111
TI  - Deep orbital Sub-Q restylane (nonanimal stabilized hyaluronic acid) for orbital
      volume enhancement in sighted and anophthalmic orbits.
AB  - OBJECTIVE: To describe a new technique of injecting Restylane Sub-Q (Q-Med,
      Uppsala, Sweden) into the intraconal and extraconal posterior orbit. METHODS:
      Retrospective review. Eight injections were performed in 5 patients using 2-mL
      Sub-Q in the intraconal and extraconal posterior orbit for orbital volume
      enhancement. Four injections were performed in sighted orbits and the remaining
      in anophthalmic orbits. The age range was 18 to 36 years; the follow-up time was
      5 to 12 months. RESULTS: Orbital volume enhancement was achieved in all cases
      with an improvement in upper eyelid sulcus and skin fold. Enophthalmos reduction
      was 2 mm per 2-mL injection. The procedure was well tolerated. One patient
      experienced a vasovagal episode lasting 3 hours and 1 patient had postoperative
      pain. No such episodes occurred after I began injecting local anesthesia before
      performing the Sub-Q injection. One patient required hyaluronidase for migrating
      gel, which caused lower eyelid swelling. CONCLUSION: This small case series
      suggested the safety and tolerability of deep orbital Sub-Q. Injections are
      easily performed in the outpatient setting. The expected volume enhancement was
      achieved in all cases with no long-term adverse effects to date.

PMID- 18071112
TI  - Cerebrospinal fluid leaks complicating orbital or oculoplastic surgery.
AB  - OBJECTIVES: To report cerebrospinal fluid (CSF) leakage as an unusual
      complication following orbital or oculoplastic procedures and to describe its
      diagnosis and management. METHODS: Retrospective case review. RESULTS: Three
      cases of CSF leaks are described in patients following orbital or oculoplastic
      procedures. Two patients developed CSF leaks after orbital decompression surgery
      for compressive optic neuropathy and 1 patient had a CSF leak following endonasal
      dacryocystorhinostomy. In the first case, high-resolution computed tomography
      confirmed the site of the leak that required surgical repair. In the second case,
      a beta(2)-transferrin test result confirmed the presence of CSF in the nasal
      drip, and coronal computed tomography identified a small fracture near the fovea
      ethmoidalis, but the leak resolved within 2 days of bed rest. In the third case,
      the patient reported several days of nasal dripping, but the problem had already
      resolved at the first follow-up appointment. CONCLUSIONS: A CSF leak following
      certain orbital and oculoplastic procedures is a rare but well-recognized
      complication. This case report reviews the mechanisms, diagnostic techniques, and
      staged management of CSF leaks.

PMID- 18071113
TI  - Frog eyes.

PMID- 18071114
TI  - Noninvasive dynamic magnetic resonance angiography with Time-Resolved Imaging of
      Contrast KineticS (TRICKS) in the evaluation of orbital vascular lesions.
AB  - OBJECTIVE: To evaluate the clinical utility of time-resolved contrast-enhanced
      magnetic resonance angiography (MRA) in the evaluation of vascular orbital
      tumors. METHODS: Retrospective medical record review of patients with vascular
      orbital lesions imaged with Time-Resolved Imaging of Contrast KineticS (TRICKS;
      GE Healthcare [Chalfont St Giles, England]) MRA, a noninvasive dynamic imaging
      modality. RESULTS: Five patients with orbital vascular tumors were evaluated
      using TRICKS MRA. These included 1 patient with a cavernous hemangioma, 2
      patients with orbital varices, 1 patient with an orbitocutaneous arteriovenous
      malformation, and 1 patient who had a solitary fibrous tumor with features of a
      hemangiopericytoma. In 2 patients, diagnoses were altered as a result of TRICKS
      MRA. In addition, a young patient with a large orbitocutaneous arteriovenous
      malformation involving the ophthalmic artery was followed perioperatively and
      noninvasively using TRICKS MRA, which produced exquisite images and added
      substantial value in the care of these patients. CONCLUSION: Dynamic MRA in the
      form of TRICKS is a newly available imaging modality with great potential for
      improving the evaluation and management of patients with complex orbital tumors.

PMID- 18071115
TI  - Long-term risk of recurrence after intact excision of pleomorphic adenomas of the
      lacrimal gland.
AB  - OBJECTIVE: To ascertain the need for follow-up after excision of pleomorphic
      adenoma of the lacrimal gland. METHODS: Medical records were reviewed for 133
      patients and only those patients with 5 years or more of follow up were
      classified into the following 5 subgroups: those with intact excision (group IA,
      n = 46), those with surgically intact excision but areas of complete attenuation
      of the pseudocapsule at histologic analysis (group IB, n = 7), those with
      previous inadvertent incisional biopsy (group IIA, n = 9), those with breach of
      the pseudocapsule during attempted intact excision (group IIB, n = 5), and those
      undergoing definitive surgery because of tumor recurrence after previous
      incomplete excision (group III, n = 5). RESULTS: Seventy-two patients were
      followed up longer than 5 years; there were no known tumor recurrences among 61
      patients excluded with shorter follow-up. Patients in groups IA and IB exhibited
      no tumor recurrences at 8.2 to 34.1 years of follow-up. A benign recurrence
      occurred along the superior orbital fissure in 1 patient in group IIA 12(1/2)
      years after the initial surgery and was resected. There were no recurrences in
      patients in groups IIB or III. CONCLUSIONS: Discharge would seem justified after
      intact excision of lacrimal gland pleomorphic adenoma, even when histologic
      examination shows extreme attenuation of the pseudocapsule. Long-term follow-up
      is, however, necessary when there has been tumor disruption, either inadvertently
      during previous biopsy or by capsular breach during definitive excision.

PMID- 18071116
TI  - Intraorbital injection of triamcinolone acetonide in patients with idiopathic
      orbital inflammation.
AB  - OBJECTIVE: To present findings of a pilot study on intraorbital corticosteroid
      therapy in the management of idiopathic orbital inflammation. METHODS: This
      prospective, noncomparative, interventional case series included patients with
      clinically, radiologically, and histologically confirmed idiopathic orbital
      inflammation with an anterior orbital mass. Twenty to 40 mg/mL of triamcinolone
      acetonide was injected intraorbitally (intralesionally or perilesionally) in all
      patients. The injection was repeated at 4-week intervals if complete resolution
      was not achieved. Patients were assessed for local and systemic complications of
      corticosteroid injection. Visual acuity, fundus examination, intraocular
      pressure, blood pressure, and serum glucose levels were measured at each visit.
      RESULTS: Ten patients (5 men and 5 women; mean age, 49.8 years [age range, 25-82
      years]) received treatment. In 4 patients, an orbital mass was noted; in 6
      patients, the lacrimal gland was involved (dacryoadenitis). Substantial
      improvement (1 patient) or complete resolution (8 patients) was noted during a
      follow-up of 9.8 months (range, 3-24 months). CONCLUSION: Intraorbital injection
      of a corticosteroid is an effective treatment for idiopathic orbital inflammation
      and may be considered first-line treatment in selected patients.

PMID- 18071117
TI  - Oxidative stress change by systemic corticosteroid treatment among patients
      having active graves ophthalmopathy.
AB  - OBJECTIVES: To measure the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in patients
      having active Graves ophthalmopathy (GO) and to compare this oxidative stress
      biomarker and the clinical evolution of patients after systemic corticosteroid
      treatment. METHODS: In 8 euthyroid patients having active GO, we determined the 8
      OHdG levels in urine before, during, and after intensive corticosteroid therapy.
      Clinical activity and ophthalmopathy index scores were assessed. Nine age- and
      sex-matched healthy volunteers served as control subjects. RESULTS: The mean 8
      OHdG level was statistically significantly increased in patients having active GO
      compared with that of controls (17.47 vs 5.97 ng/mg of creatinine, P < .001).
      During and after maximal systemic corticosteroid treatment, patients had
      statistically significantly lower mean 8-OHdG levels (7.19 and 10.18 ng/mg of
      creatinine, respectively) compared with the mean level before treatment. These
      changes were accompanied by decreases in clinical activity and ophthalmopathy
      index scores. The urinary 8-OHdG levels were subsequently elevated in 2 patients
      having recurrent active GO when corticosteroid therapy was tapered or withdrawn.
      CONCLUSIONS: Oxidative stress may have a role in the pathogenesis of GO. Urinary
      8-OHdG level can be used not only as a noninvasive biomarker of oxidative stress
      in patients having GO but also as an objective and quantitative parameter in the
      follow-up of patients during immunosuppressive treatment.

PMID- 18071118
TI  - Orbital and adnexal sarcoidosis.
AB  - OBJECTIVE: To present the clinical features and management in a series of
      patients with orbital and adnexal sarcoidosis. METHODS: This multicenter
      retrospective study included patients with biopsy-proven noncaseating granuloma
      involving the orbit or adnexa and evidence of systemic sarcoidosis. Clinical
      records were reviewed for initial examination findings, radiological findings,
      treatment modalities, and outcome. RESULTS: The study included 26 patients (19
      female, 7 male; mean age, 52 years). The most common feature at the first
      examination was a palpable periocular mass followed by discomfort, proptosis,
      ptosis, dry eye, diplopia, and decreased vision. The disease affected the
      lacrimal gland (42.3%), orbit (38.5%), eyelid (11.5%), and lacrimal sac (7.7%).
      Among orbital lesions, the antero-inferior quadrant was preferentially involved.
      Treatment modalities included steroids, surgical debulking, and methotrexate.
      During a mean follow-up of 18.75 months, 84.6% of patients showed a complete
      response to the treatment, but 19.2% of patients developed further signs of
      sarcoidosis. CONCLUSIONS: Orbital soft tissue involvement is more common in
      patients older than 50 years and in women. The anterior inferior quadrants of the
      orbits appear to be preferentially affected. Although a good response to
      treatment with oral steroids is seen, long-term follow-up is recommended because
      active systemic disease can develop months to years later.

PMID- 18071119
TI  - Prevalence and nature of systemic involvement and stage at initial examination in
      patients with orbital and ocular adnexal lymphoma.
AB  - OBJECTIVE: To determine the stage at initial examination and the prevalence of
      systemic involvement in patients with orbital and ocular adnexal lymphoma.
      METHODS: The medical records of all patients with orbital and ocular adnexal
      lymphoma treated in a recent 7-year period were reviewed for stage at initial
      examination, highest stage during the follow-up period, and recurrence-free
      survival. RESULTS: Forty-three patients were included. Nineteen patients had
      mucosa-associated lymphoid tissue, 9 had follicular, 9 had diffuse large-cell, 3
      had mantle cell, 2 had small lymphocytic, and 1 had large T-cell lymphoma. The
      staging workup included chest radiography; orbital computed tomography or
      magnetic resonance imaging; computed tomography of the chest, abdomen, and
      pelvis; and bone marrow biopsy. Thirty-six patients had total body positron
      emission tomography, 7 had gallium scans, and 16 had gastrointestinal endoscopy.
      Lymphoma stage at diagnosis was IE in 18 patients, II in 6, and IV in 19. Six of
      19 patients with mucosa-associated lymphoid tissue, 7 of 9 patients with
      follicular, 6 of 9 patients with diffuse large-cell, and 3 of 3 patients with
      mantle cell lymphoma had non-stage IE disease at initial examination. The 5-year
      recurrence-free survival was 64.6% for the entire cohort. CONCLUSIONS:
      Extraorbital involvement is present at diagnosis in more than half of patients
      with orbital and ocular adnexal lymphoma and warrants extensive systemic workup
      at diagnosis, continued surveillance, and consideration of systemic therapy.

PMID- 18071120
TI  - Lymphoproliferative diseases of the ocular adnexa in Korea.
AB  - OBJECTIVES: To evaluate the clinical features, treatments, and outcomes of
      patients with ocular lymphoproliferative disease classified according to the
      World Health Organization classification and to determine prognostic factors of
      this disease in South Korea. METHODS: Between March 1, 1995, and December 31,
      2005, 128 cases of patients with ocular lymphoid tumors treated at the Samsung
      Medical Center were retrospectively reviewed. RESULTS: The mean patient age was
      46.3 years (range, 1-87 years). The major histopathologic subtypes were mucosa
      associated lymphoid tissue (MALT) lymphoma in 96 patients (75.0%), lymphoid
      hyperplasia in 11 (8.6%), diffuse large B-cell lymphoma in 6 (4.7%), and mantle
      cell lymphoma in 4 (3.1%). Ocular lymphoproliferative lesions were located in the
      conjunctiva (53 patients), the eyelid (33 patients), and the orbit (42 patients).
      Twenty patients had tumor relapses (15.6%), and 9 died of lymphoma during follow
      up (7.0%). Regarding the analysis of prognostic factors, most patients with MALT
      lymphoma evidenced local disease, required local treatment, and exhibited a
      superior prognosis. CONCLUSIONS: Lymphomas of the MALT type constitute most
      ocular adnexal lymphoproliferative diseases and occur more frequently in South
      Korea than in Western countries. Patients with MALT lymphoma have favorable
      outcomes compared with patients with other types of lymphoma.

PMID- 18071121
TI  - Air reflux after external dacryocystorhinostomy.
AB  - OBJECTIVE: To ascertain the prevalence of air reflux after external
      dacryocystorhinostomy, its natural history, and its relation to symptomatic cure.
      METHODS: More than a year after lacrimal surgery, patients were contacted via a
      structured telephone interview and were questioned about air reflux and lacrimal
      symptoms. RESULTS: Interviews were completed by 77 patients (98 operations).
      Postoperative air reflux had been noted after 46 of 98 operations (47%) and
      persisted in 36 of 46 eyes (78%), at a mean follow-up of 58 months. Reflux
      occurred in 36% (8 of 22) of eyes after membranectomy, a rate similar to that
      without membranectomy (38 of 76 eyes; [50%]); the relative risk of air reflux
      with membranectomy was 0.7 (95% confidence interval, 0.4-1.3; P = .30). Overall,
      symptomatic improvement was achieved in 85% of procedures (83 eyes). Reflux was
      associated with a higher success rate (relative risk, 1.22; P = .02) and was
      significantly less likely to be associated with unchanged or worse symptoms
      (relative risk of failure, 0.28; P = .03). CONCLUSIONS: Air reflux is common
      after external dacryocystorhinostomy, is associated with symptomatic success, and
      generally persists but is rarely troublesome. Membranectomy does not increase the
      incidence of reflux, suggesting that the valve of Rosenmuller may not act as a 1
      way valve for air flow.

PMID- 18071122
TI  - Sex and age differences in the bony nasolacrimal canal: an anatomical study.
AB  - OBJECTIVES: To determine the diameters of the bony nasolacrimal canal and to
      evaluate how they are affected by sex and age. METHODS: Standard axial sinus
      computed tomographic images of 314 patients were assessed retrospectively; the
      anteroposterior and transverse diameters, the sectional area of the bony
      nasolacrimal canal at the level of the infraorbital margin, and the angle between
      the bony canal and the nasal floor were measured. RESULTS: The mean results were
      as follows: anteroposterior diameter, 5.6 mm; transverse diameter, 5.0 mm;
      sectional area of the bony nasolacrimal canal, 22.6 mm(2); and angle between the
      bony canal and the nasal floor, 78.3 degrees . Females had a significantly
      smaller anteroposterior diameter (mean 0.6 mm) and a significantly smaller
      transverse diameter (mean 0.3 mm). The sectional area of the bony nasolacrimal
      canal was 13% smaller in females (P < .001). The angle between the bony canal and
      the nasal floor was a mean of 1.1 degrees more obtuse in males (P = .004). With
      age, the transverse diameter, the sectional area of the bony nasolacrimal canal,
      and the angle between the bony canal and the nasal floor in males, and the
      anteroposterior diameter, the sectional area of the bony nasolacrimal canal, and
      the angle between the bony canal and the nasal floor in females increased
      significantly. CONCLUSIONS: In females, the narrowness of the bony nasolacrimal
      canal and the acute angle between the bony canal and the nasal floor predispose
      to chronic inflammation of the nasolacrimal drainage system. The results of this
      quantitative anatomical study may explain why primary acquired nasolacrimal duct
      obstruction is more frequent in younger female patients.

PMID- 18071123
TI  - Dissociated horizontal deviation after surgery for infantile esotropia: clinical
      characteristics and proposed pathophysiologic mechanisms.
AB  - OBJECTIVE: To examine the results of reversed fixation testing in patients who
      develop consecutive exotropia after surgery for infantile esotropia. METHODS: The
      reversed fixation test was performed prospectively in 28 patients who developed
      consecutive exotropia after surgery for infantile esotropia. All patients were
      assessed for adduction weakness, latent nystagmus, dissociated vertical
      divergence, and neurologic disease. RESULTS: A positive reversed fixation test,
      indicating the presence of dissociated horizontal deviation, was found in 14 of
      28 patients (50%) with consecutive exotropia. In patients with dissociated
      horizontal deviation, the exodeviation was usually smaller with the nonpreferred
      eye fixating than with the preferred eye fixating, and smaller with the preferred
      eye fixating than during periods of visual inattention or under general
      anesthesia. Dissociated horizontal deviation correlated with the findings of
      dissociated vertical divergence, but not with asymmetric adduction weakness,
      latent nystagmus, or neurologic disease. CONCLUSIONS: Dissociated horizontal
      deviation is a clinical expression of dissociated esotonus. The common clinical
      presentation of dissociated horizontal deviation as an intermittent exodeviation
      of 1 eye results from the superimposition of a dissociated esotonus on a baseline
      exodeviation.

PMID- 18071124
TI  - Keratocyte density and recovery of subbasal nerves after penetrating keratoplasty
      and in late endothelial failure.
AB  - OBJECTIVE: To determine central keratocyte and subbasal nerve densities in clear
      and failed grafts after penetrating keratoplasty. METHODS: Clear grafts and
      grafts with late endothelial failure (LEF) were examined using confocal
      microscopy 1 to 31 years after penetrating keratoplasty. Keratocyte density,
      number of keratocytes in a full-thickness column of stroma, and subbasal nerve
      density were determined from images. Comparisons were made with normal corneas.
      RESULTS: The mean +/- SD keratocyte density in clear grafts (22 101 +/- 3799
      cells/mm(3)) was lower than that in normal corneas (26 610 +/- 3683 cells/mm(3);
      P < .001) but did not differ from that in grafts with LEF (21 268 +/- 3298
      cells/mm(3); P = .47). The mean +/- SD number of keratocytes in clear grafts (10
      325 +/- 1708 cells) was lower than that in normal corneas (11 466 +/- 1503 cells;
      P < .001) but did not differ from that in grafts with LEF (10 778 +/- 1760 cells;
      P = .39). Median subbasal nerve density in clear grafts (150 microm/mm(2)) was
      lower than that in normal corneas (7025 microm/mm(2); P < .001), and nerve
      recovery correlated with time after surgery (r = 0.36; P < .001). CONCLUSIONS:
      Keratocyte density and number are decreased in penetrating grafts compared with
      normal corneas. Subbasal nerve density does not recover to normal through 3
      decades.

PMID- 18071125
TI  - Superior ophthalmic vein cannulation through a lateral orbitotomy for
      embolization of a cavernous dural fistula.
AB  - Many embolization procedures have been described for the treatment of cavernous
      dural fistulas, including direct superior ophthalmic vein cannulation. Sometimes
      thrombosis of the superior ophthalmic vein or an anatomic variant will not allow
      its cannulation. Herein, we describe a case of a cavernous dural fistula in which
      an anteriorly narrowed and thrombosed superior ophthalmic vein was cannulated in
      the deep orbit through a lateral orbitotomy.

PMID- 18071126
TI  - Does infantile esotropia arise from a dissociated deviation?
AB  - Tonus refers to the effects of baseline innervation on musculature in the awake,
      alert state.(1) Since the normal anatomical resting position of the eyes is one
      of exodeviation, extraocular muscle tonus plays a vital physiologic role in
      establishing ocular alignment. Under normal conditions, binocular esotonus is
      superimposed on the baseline anatomical position of rest to maintain approximate
      ocular alignment, save for a minimal exophoria that is easily overcome by active
      convergence. When binocular visual input is preempted early in life, monocular
      fixation may give rise to a larger dissociated esotonus that gradually drives the
      2 eyes into a "convergent" position, resulting in infantile esotropia.(2).

PMID- 18071127
TI  - The orbital and ophthalmic plastic surgery theme issue.

PMID- 18071128
TI  - A personal view: probability in medicine, levels of (Un)certainty, and the
      diagnosis of orbital disease (with particular reference to orbital
      "pseudotumor").

PMID- 18071129
TI  - Use of radiopaque intraorbital catheter in the treatment of sino-orbito-cranial
      mucormycosis.

PMID- 18071130
TI  - Risk factors for contact lens related fusarium keratitis.

PMID- 18071131
TI  - The GLC1H glaucoma locus may reflect glaucoma with elevated intraocular pressure.

PMID- 18071133
TI  - The eyes, brain, bones, and skull of Johann Sebastian Bach.

PMID- 18071135
TI  - Pearls and oy-sters of localization in ophthalmoparesis.
AB  - Ocular misalignment and ophthalmoparesis result in the symptom of binocular
      diplopia. In the evaluation of diplopia, localization of the ocular motility
      disorder is the main objective. This requires a systematic approach and knowledge
      of the ocular motor pathways and actions of the extraocular muscles. This article
      reviews the components of the ocular motor pathway and presents helpful tools for
      localization and common sources of error in the assessment of ophthalmoparesis.

PMID- 18071136
TI  - Clinical reasoning: a 59-year-old woman with acute paraplegia.

PMID- 18071139
TI  - Dementia: many roads, but not built in a day.

PMID- 18071140
TI  - Preserved cognitive functioning over time in asymptomatic HIV-infected people in
      the MACS cohort.

PMID- 18071141
TI  - Multicenter assessment of CSF-phosphorylated tau for the prediction of conversion
      of MCI.
AB  - BACKGROUND: The measurement of hyperphosphorylated tau (p-tau) in CSF has been
      proposed as a biomarker candidate for the prediction of Alzheimer disease (AD) in
      patients with mild cognitive impairment (MCI). However, a standard quantitative
      criterion of p-tau has not been evaluated. OBJECTIVE: To assess in a multicenter
      study the predictive accuracy of an a priori defined criterion of tau
      phosphorylated at threonine 231 (p-tau(231)) for the prediction of conversion
      from MCI to AD during a short-term observation interval. METHODS: The study
      included 43 MCI converters, 45 stable MCI (average follow-up interval = 1.5
      years), and 57 healthy controls (at baseline only). Subjects were recruited at
      four international expert sites in a retrospective study design. Cox regression
      models stratified according to center were used to predict conversion status.
      Bootstrapped 95% CIs of classification accuracy were computed. RESULTS: Levels of
      p-tau(231) were a significant predictor of conversion (B = 0.026, p = 0.001),
      independent of age, gender, Mini-Mental State Examination, and ApoE genotype. For
      an a priori-defined cutoff point (27.32 pg/mL), sensitivity ranged between 66.7
      and 100% and specificity between 66.7 and 77.8% among centers. The bootstrapped
      mean percentage of correctly classified cases was 79.95% (95% CI = 79.9 to
      80.00%). Post hoc defined cutoff values yielded a mean bootstrapped
      classification accuracy of 80.45% (95% CI = 80.24 to 80.76%). CONCLUSIONS: An a
      priori defined cutoff value of p-tau(231) yields relatively stable results across
      centers, suggesting a good feasibility of a standard criterion of p-tau(231) for
      the prediction of Alzheimer disease.

PMID- 18071142
TI  - Rating the approachability of faces in ALS.
AB  - BACKGROUND: Several groups have found that a significant percentage of patients
      with amyotrophic lateral sclerosis (ALS) have cognitive impairment. Here we
      investigate whether the amygdala, a temporal lobe structure, is affected by ALS.
      METHODS: We asked patients with ALS to judge the approachability of unfamiliar
      faces. We showed subjects 60 faces and asked, "If you were in a strange town at
      dusk, would you ask this person for directions to a hotel?" RESULTS: More than
      half of our patients had similar behavioral characteristics to patients with
      bilateral amygdala damage, approaching even faces that controls found
      unapproachable. This pattern was not associated with frontal lobe dysfunction on
      neuropsychological testing. DISCUSSION: Patients with amyotrophic lateral
      sclerosis (ALS) rated highly approachable faces similarly to controls but rated
      many faces approachable that controls deemed unapproachable. Like patients with
      amygdala damage, who show the same behavior, patients with ALS may not recognize
      the threat expressed through facial clues that raise concern in controls. Thus,
      more patients with ALS may have disease involvement outside of the motor cortex
      than previously suggested, manifesting as frontal lobe, temporal lobe, or frontal
      and temporal lobe dysfunction.

PMID- 18071143
TI  - Clinical, electrophysiologic, and pathologic evidence for sensory abnormalities
      in ALS.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive degenerative
      disease of upper and lower motor neurons. Reports of the nature and frequency of
      sensory nerve involvement in ALS have varied. METHODS: We reviewed the Emory
      University motor neuron disease registry between 1997 and 2004 to identify 103
      patients with ALS without coexisting diseases that might cause sensory
      abnormalities and for whom electrodiagnostic studies were available for review.
      Neurophysiologic studies were interpreted based on age-adjusted normative data
      from our laboratory. Twelve control biopsies were evaluated alongside 22 samples
      from patients with ALS to ensure blinded evaluation of pathologic specimens.
      RESULTS: Sensory symptoms or signs were present in 32% of patients, sural sensory
      nerve action potential amplitudes were abnormal in 27%, and pathologic
      abnormalities were present in 91% of patients. Large-caliber myelinated fibers
      were predominantly affected (reduced in 73%) and small-caliber myelinated fibers
      were affected less often (23%). Thinly myelinated fibers were present in 95% and
      regenerating clusters in 77% of the biopsies. Teased fiber analysis showed an
      increased frequency of axonal degeneration and regeneration as well as excessive
      myelin irregularity. Morphometry confirmed the loss of large-caliber fibers.
      CONCLUSIONS: These data indicate that one third of patients with amyotrophic
      lateral sclerosis report sensory symptoms and sural sensory response amplitudes
      are reduced in a similar proportion of subjects. Pathologic evidence of sensory
      nerve pathology was present in 91% of patients who underwent sural nerve biopsy.
      The electrophysiologic and pathologic findings indicate a pattern of axonal loss
      that predominantly affects large-caliber myelinated fibers.

PMID- 18071144
TI  - Physical health-related quality of life predicts stroke in the EPIC-Norfolk.
AB  - OBJECTIVE: To examine the relationship between Short Form (SF)-36 physical
      functional health-related quality of life and incident stroke. METHODS: A total
      of 13,615 men and women participating in the European Prospective Investigation
      into Cancer-Norfolk who were free of stroke, myocardial infarction, and cancer at
      baseline were included in the study. Participants completed a health and
      lifestyle questionnaire and attended a health examination during 1993 to 1997.
      Self-reported physical functional health was assessed using physical component
      summary scores of SF-36 18 months later. Stroke incidence was ascertained by
      death certification and hospital record linkage up to 2005. RESULTS: There were
      244 incident strokes (total person years = 99,191). People who reported better
      physical functional health had significantly lower risk of incident stroke. Using
      Cox proportional hazard models adjusting for age, sex, body mass index, systolic
      blood pressure, cholesterol, smoking, diabetes, physical activity, social class,
      alcohol consumption, and respiratory function, men and women who were in the top
      quartile of SF-36 physical component summary scores had half the risk of stroke
      (RR = 0.50 [0.31, 0.78]) compared to the people in the bottom quartile. The
      relationships remained unchanged after excluding strokes occurring within the
      first 2 years of follow-up. CONCLUSIONS: Physical functional health-related
      quality of life measured as Short Form-36 predicts subsequent stroke risk
      independently of known risk factors in a general population. Poor physical
      functional health may indicate a high-risk population for stroke who may benefit
      most from targeted preventive interventions such as management of known risk
      factors.

PMID- 18071145
TI  - Cardiovascular autonomic function in poststroke patients.
AB  - BACKGROUND: Autonomic dysregulation is frequent in acute ischemic stroke. Several
      studies concluded that imbalance between sympathetic and parasympathetic
      cardiovascular function predisposes to malignant cardiac arrhythmia. However,
      there are few data on cardiovascular autonomic function in post-acute stroke
      patients. OBJECTIVE: To study cardiovascular autonomic function 18 to 43 months
      after lacunar stroke. PATIENTS AND METHODS: We continuously monitored R-R
      intervals (RR(int)), mean blood pressure (BP(mean)), and respiration in 15
      patients (8 women, aged 43 to 73 years) after right-sided stroke, in 13 patients
      (7 women, aged 50 to 75 years) after left-sided stroke, and in 21 age- and sex
      matched controls at rest. We used autoregressive spectral analysis to assess
      sympathetic and parasympathetic modulation as powers of RR(int) and BP(mean)
      oscillations in the low-frequency (LF: 0.04 to 0.15 Hz) and high-frequency bands
      (HF: 0.15 to 0.5 Hz). RESULTS: Mean values of RR(int), BP(mean), and respiratory
      frequency did not differ between patients after right- or left-sided stroke and
      controls (p > 0.05). Patients after right-sided stroke showed a trend toward
      elevated LF power of RR(int) as compared with patients after left-sided stroke
      and controls (p < 0.10). HF powers of RR(int) were reduced in patients after
      right- and left-sided stroke as compared with controls (p < 0.05). LF/HF ratio of
      RR(int) was elevated in patients after right-sided stroke as compared with
      patients after left-sided stroke and controls (p < 0.05). CONCLUSION:
      Irrespective of the side of the ischemia, post-acute stroke patients showed a
      parasympathetic cardiac deficit. Additionally, sympathetic cardiovascular
      modulation was increased in patients after right-sided stroke. Post-acute stroke
      patients might be at an increased risk for cardiac arrhythmia after unopposed
      sympathetic stimulation.

PMID- 18071146
TI  - A subcortical network of dysfunction in TLE measured by magnetic resonance
      spectroscopy.
AB  - OBJECTIVE: The goal of this work was to evaluate the relationship between
      neuronal injury/loss in the hippocampus, thalamus, and putamen in temporal lobe
      epilepsy (TLE) patients using (1)H magnetic resonance spectroscopic imaging.
      METHODS: (1)H spectroscopic images from the hippocampus and thalamus of controls
      and patients with TLE were acquired at 4 T. The spectroscopic imaging data were
      reconstructed using an automated voxel-shifting method based on anatomic
      landmarks providing four, six, and three loci for the hippocampus, thalamus, and
      putamen, respectively. For correlation analysis, the hippocampal and striatal
      loci were averaged to provide single estimates of the entire structure, whereas
      the thalamus was divided into two regions, an anterior and posterior measure,
      using the average of three loci each. RESULTS: The ratio of N-acetyl aspartate to
      creatine (NAA/Cr), a measure of neuronal injury/loss, was significantly reduced
      in both the ipsilateral and contralateral hippocampi and thalami. NAA/Cr in the
      ipsilateral hippocampus was significantly correlated with the ipsilateral and
      contralateral anterior and posterior thalami, putamen, and contralateral
      hippocampus. In control subjects, the hippocampi were only correlated with each
      other. CONCLUSIONS: The data demonstrate that there is significant neuronal
      injury/loss in both the ipsilateral and contralateral thalami in temporal lobe
      epilepsy patients, with greater impairment in the anterior portions of the
      ipsilateral thalamus. The degree of injury/loss in the ipsilateral and
      contralateral thalamus and putamen is directly correlated with that of the
      ipsilateral hippocampus. This is consistent with the hypothesis that the
      impairment and damage associated with recurrent seizures as measured by N-acetyl
      aspartate originating in the hippocampus results in injury and impairment in
      other subcortical structures.

PMID- 18071147
TI  - Aquaporin-4, homeostasis, and neurologic disease.

PMID- 18071148
TI  - Reflections: neurology and the humanities. Whose side are you on?

PMID- 18071150
TI  - The family conference: end-of-life guidelines at work for comatose patients.

PMID- 18071151
TI  - Parry Romberg syndrome and linear scleroderma en coup de sabre mimicking
      Rasmussen encephalitis.

PMID- 18071152
TI  - Importance of monotherapy in women across the reproductive cycle.
AB  - Special treatment considerations are warranted in women with epilepsy,
      particularly those of childbearing age. Treatment guidelines generally recommend
      the use of antiepileptic drug (AED) monotherapy at the lowest dose possible
      during pregnancy. The UK Epilepsy and Pregnancy Register reported that the risk
      for major congenital malformations is higher with AED polytherapy than with
      monotherapy (6.0% vs 3.7%, respectively) and that valproate carries the highest
      individual risk. The AEDs that induce hepatic cytochrome CYP450 enzymes carry
      particular concern both before and after pregnancy. Hepatic enzyme inducers alter
      steroid metabolism in women receiving oral contraceptives, increase the risk for
      contraceptive failure, and interfere with calcium absorption and vitamin D
      metabolism, thus increasing the risk for osteoporosis and fractures. Vitamin K
      deficiency is another potential consequence of treatment with a hepatic enzyme
      inducing AED, increasing the risk for coagulopathy and neonatal intraparenchymal
      and intracerebral hemorrhage during the first 24 hours of life. Supplemental
      vitamin K therapy during the last month of pregnancy is warranted.
      Preconceptional and gestational folate supplementation may also be warranted to
      prevent neural tube malformation related to AED treatment. Because AED
      pharmacokinetics may be altered during pregnancy, plasma AED concentrations
      should be measured before conception and monthly during pregnancy to prevent
      seizure breakthrough.

PMID- 18071153
TI  - Monotherapy in children and infants.
AB  - An expanding array of antiepileptic drugs (AEDs) is available to treat childhood
      epilepsy, offering the potential for improved seizure control and quality of life
      in this important patient population but also providing challenges in the
      selection of the best regimen for the individual patient. In addition to correct
      diagnosis of seizure type and general AED efficacy profile, other important
      treatment considerations in pediatric patients include age-specific organ
      toxicity, potential cognitive and behavioral or psychiatric effects of AEDs,
      compliance, and drug-drug interactions, since children commonly receive more
      medications than nonelderly adults. Drug dosing may be more difficult in
      pediatric than in adult epilepsy patients, and doses in children often require
      adjustment as the patient matures. Because many randomized controlled trials
      (RCTs) of newer AEDs have not included childhood epilepsy, physicians often have
      incomplete data on which to base treatment decisions. Therefore, despite the
      wider array of potential therapies, it is often unclear how to realize the
      potential they offer. Recently published guidelines from a number of
      organizations have provided strategies for the use of new AEDs in the treatment
      of childhood epilepsy. Additional RCTs of monotherapy options for childhood
      epilepsy are greatly needed. The ketogenic diet provides an alternative to
      pharmacologic control of seizures in some pediatric patients.

PMID- 18071154
TI  - Monotherapy clinical trial design.
AB  - Monotherapy of epilepsy is usually preferable to polytherapy for a variety of
      reasons. However, investigational or newer antiepileptic drugs (AEDs) are
      typically evaluated as add-on therapy in patients with refractory seizures.
      Because coadministered drugs are subject to drug interactions, add-on trials of
      AEDs do not necessarily address the utility of a new AED as monotherapy or its
      use in patients with newly diagnosed epilepsy, in whom monotherapy is usually
      sufficient. Monotherapy clinical trials are difficult to design because
      randomizing epilepsy patients to placebo or pseudoplacebo is considered
      unethical, and results from active-drug noninferiority designs are difficult to
      interpret. Active-drug superiority designs have been developed in an attempt to
      provide useful information about the monotherapeutic efficacy of new AEDs. The
      conversion to monotherapy trial design, introduced in the late 1970s, provides
      for initial add-on of an investigational agent to a preexisting drug in patients
      with uncontrolled seizures, followed by gradual discontinuation of the
      preexisting treatment and an eventual monotherapy phase of the investigational
      agent. Conversion to monotherapy trials are typically of short duration and have
      been criticized for failing to provide adequate time for titration to optimal
      dose, an inability to examine tolerance development or long-term safety, and
      possibly placing enrolled patients at increased risk for morbidity, but they have
      been used to obtain data about monotherapy efficacy sufficient for regulatory
      authority approval. Relevant clinical trial data are needed to guide treatment
      choices in patients who have failed previous monotherapy. To date, large-scale
      prospective trials comparing monotherapy with old and new AEDs have not shown
      superior efficacy of the new AEDs but have demonstrated their better tolerability
      and safety. It is hoped that use of appropriately designed monotherapy clinical
      trials will help to identify a new generation of AEDs in the future for
      monotherapy in epilepsy patients.

PMID- 18071155
TI  - Animal model studies application to human patients.
AB  - Animal models are used to identify potential new antiepileptic drugs (AEDs) and
      to study the effects of combining AEDs with different mechanisms of action. The
      models most commonly used to identify new AEDs are the maximal electroshock (MES)
      test, the subcutaneous pentylenetetrazol (PTZ) test, and the electrical kindling
      model. The MES test has been useful in identifying agents that block generalized
      tonic-clonic seizures by prolonging the inactivation of sodium channels. The PTZ
      model has proved to be a good predictor of clinical efficacy of generalized spike
      wave epilepsies of the absence type, and agents that reduce the calcium flow
      through T-type calcium channels or that enhance chloride flow through GABA(A)
      receptors are effective in this model. Electrically or chemically induced
      kindling is a model of epileptogenesis and has been used to study the
      epileptogenic process and the molecules that interfere with this process. Many
      epilepsy patients who fail to achieve adequate seizure control with different
      monotherapy agents and are unsuitable for surgical management are given
      polytherapy. Animal models can be used to evaluate different combinations of AEDs
      before their use in humans. Initial studies have identified combinations
      associated with supra-additive anticonvulsant effects that may warrant further
      study.

PMID- 18071156
TI  - Monotherapy in adults and elderly persons.
AB  - Treatment of epilepsy with a single drug has many advantages. Potential benefits
      of monotherapy vs polytherapy include fewer adverse events and better
      tolerability, avoidance of drug-drug interactions, reduced treatment costs, and
      improved compliance. Initial treatment should always be monotherapy. Avoidance of
      pharmacokinetic interactions is a major advantage. Some patients who have
      achieved seizure control with polytherapy may be candidates for conversion to
      monotherapy because there is no conclusive evidence that polytherapy provides
      better seizure control in the majority of patients. Recently published treatment
      guidelines that take into account the efficacy and tolerability profiles of new
      and old antiepileptic drugs (AEDs) provide recommendations for drug selection in
      adults. Elderly patients with epilepsy face unique treatment challenges, which
      include age-related reductions in liver or kidney function that may alter drug
      pharmacokinetics. Older persons are more sensitive to CNS side effects; some
      drugs may exacerbate preexisting problems such as tremor, ataxia, and cognitive
      difficulty. Many common conditions in the elderly are treated with drugs that are
      subject to interactions with AEDs. Complex dosing schedules and high drug costs
      are often barriers to proper care. For all these reasons, monotherapy is
      especially attractive for the elderly.

PMID- 18071158
TI  - Why the slow diffusion of treatment guidelines into clinical practice?

PMID- 18071159
TI  - The challenge of women and heart disease.

PMID- 18071160
TI  - Coronary heart disease risk assessment by traditional risk factors and newer
      subclinical disease imaging: is a "one-size-fits-all" approach the best option?

PMID- 18071161
TI  - Symptom presentation of women with acute coronary syndromes: myth vs reality.
AB  - BACKGROUND: Optimal diagnosis and timely treatment of patients with an acute
      coronary syndrome (ACS) depends on distinguishing differences between popular
      "myths" about ischemic symptoms in women and men. Chest pain or discomfort is
      regarded as the hallmark symptom of ACS, and its absence is regarded as
      "atypical" presentation. This review describes the presenting symptoms of ACS in
      women compared with men and ascertains whether women should have a symptom
      message that is separate or different from that for men. METHODS: MEDLINE (1970
      2005), bibliographies of articles, and pertinent abstracts were reviewed,
      focusing on studies of ACS presentation, especially those reporting differences
      in symptoms by sex. This analysis included 69 of 361 possible studies. Data
      regarding symptom presentation were recorded. RESULTS: The published literature
      lacks standardization in characterizing ACS presentation, data collection, and
      reporting of symptoms. Approximately one-third of patients in the large cohort
      studies and one-quarter of patients in the smaller reports and direct patient
      interviews presented without chest pain or discomfort. The absence of chest pain
      or discomfort with ACS was noted more commonly in women than in men in both the
      cumulative summary from large cohort studies (37% vs 27%) and the single-center
      and small reports or interviews (30% vs 17%). CONCLUSIONS: Women are
      significantly less likely to report chest pain or discomfort compared with men.
      These differences, however, are not likely large enough to warrant sex-specific
      public health messages regarding the symptoms of ACS at the present time. Further
      research must systematically investigate sex differences in the clinical
      presentation of ACS symptoms and must include standardized data collection
      efforts.

PMID- 18071162
TI  - Early risk of stroke after transient ischemic attack: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Recent observational studies suggest that the risk for stroke may be
      high in the first 90 days after transient ischemic attack (TIA). This finding
      may, however, not be consistent across existing studies assessing stroke risk
      after TIA. The objectives of our study were to conduct a systematic review and
      meta-analysis of observational studies estimating the risk of stroke at 2, 30,
      and 90 days after TIA and to explore clinical and methodological factors that may
      explain variability in findings across studies. METHODS: Articles were obtained
      by searching the Cochrane Database of Systematic Reviews (1996 to present),
      MEDLINE (1966 to present), EMBASE (1980 to present), CINAHL (1982 to present),
      and BIOSIS previews (1980 to present). Searches were supplemented by scanning
      bibliographies of included articles, review articles, and conference proceedings
      and by contacting an expert in the field. Abstracts were retained if they
      reported original data and addressed early risk of stroke in patients with TIA.
      We identified 51 candidate studies reporting early risk of stroke after TIA. Two
      reviewers independently extracted information from 11 selected studies.
      Indicators of study quality were collected and included consecutive enrollment,
      losses to follow-up, explicit criteria used to define TIA and stroke, and method
      of ascertainment. Pooled early risk of stroke was estimated using fixed and
      random effects models, and meta-regression was used to assess the association
      between clinical and methodological factors and the reported early risk of
      stroke. RESULTS: Based on a random effects model, the pooled early risk of stroke
      was 3.5%, 8.0%, and 9.2% at 2, 30, and 90 days after TIA, respectively. Studies
      reported higher risks when the methodology involved active ascertainment of
      stroke outcome compared with passive ascertainment. Early risk of stroke was
      9.9%, 13.4%, and 17.3% at 2, 30, and 90 days, respectively, when only studies
      with active outcome ascertainment were considered. CONCLUSIONS: Transient
      ischemic attack is associated with high early risk of stroke. The methodological
      design of studies accounts for some of the variability seen in previous reports
      of early stroke risk after TIA.

PMID- 18071163
TI  - Intravenous low-molecular-weight heparins compared with unfractionated heparin in
      percutaneous coronary intervention: quantitative review of randomized trials.
AB  - BACKGROUND: Despite its limitations, unfractionated heparin (UFH) is the
      recommended anticoagulant during percutaneous coronary intervention (PCI). Few
      randomized trials have compared low-molecular-weight heparin (LMWH) and UFH, and
      most lacked the power to detect a difference between the 2 anticoagulants in
      terms of safety or efficacy. Our objective was to perform a meta-analysis of
      randomized trials comparing the efficacy and safety of LMWH vs UFH as
      anticoagulants in the setting of PCI. METHODS: We used MEDLINE, randomized trials
      presented at major cardiology conferences, and journal article bibliographies
      from January 1998 and September 2006. Two reviewers independently identified
      randomized studies comparing the intravenous administration of LMWH vs UFH among
      patients undergoing PCI. Data on sample size, baseline characteristics, and
      outcomes of interest were independently extracted and analyzed. RESULTS: Thirteen
      trials including 7318 patients met the inclusion criteria. A total of 4201
      patients (57.4%) received LMWH, and 3117 patients (42.6%) received UFH.
      Intravenous LMWH use was associated with a significant reduction in the risk of
      major bleeding compared with UFH (odds ratio [OR], 0.57; 95% confidence interval
      [CI], 0.40-0.82; P = .002). A trend toward a reduction in minor bleeding was also
      observed among LMWH-treated patients (OR, 0.75; 95% CI, 0.47-1.20; P = .24).
      Similar efficacy was observed between LMWH and UFH regarding the double end point
      of death or myocardial infarction (OR, 0.99; 95% CI, 0.79-1.24; P = .93). There
      were no significant differences in death, myocardial infarction, and urgent
      revascularization between patients receiving LMWH and those receiving UFH.
      CONCLUSION: The use of intravenous LMWH during PCI is associated with a
      significant reduction in major bleeding events compared with UFH, without
      compromising outcomes on hard ischemic end points.

PMID- 18071164
TI  - Inadequate control of hypertension in US adults with cardiovascular disease
      comorbidities in 2003-2004.
AB  - BACKGROUND: Cardiovascular risks associated with hypertension (HTN) and the
      importance of its control are well established; however, the prevalence and
      adequacy of its treatment and control in persons with cardiovascular
      comorbidities (CVCs) are uncertain. METHODS: To examine the prevalence,
      treatment, and control of HTN among US adults with and without CVCs, we analyzed
      data from adults at least 18 years of age (n = 4646, N [projected sample size] =
      192.4 million) in the National Health and Nutrition Examination Survey 2003-2004,
      a nationally representative cross-sectional survey of the noninstitutionalized
      civilian US population. Prevalence, treatment, and control rates of HTN in
      patients with CVCs vs those without, including coronary artery disease,
      congestive heart failure, stroke, chronic kidney disease, peripheral artery
      disease, and diabetes mellitus, and distance to blood pressure goal in those
      whose HTN was not controlled were the main outcomes. RESULTS: The overall
      prevalence rate of HTN was 31.4% (n = 1671, N = 60.5 million), ranging from 23.1%
      in those without CVCs to 51.8% to 81.8% in those with CVCs (P < .01). Despite HTN
      treatment rates for diabetes mellitus, stroke, heart failure, and coronary artery
      disease that are higher (83.4%-89.3%) than the rates of those without these
      conditions (66.5%) (P < .01), control rates for treatment remained poor (23.2%
      49.3%) (P < .001 to P = .048). Isolated systolic HTN was the most common
      hypertensive subtype in those with CVCs (> or = 63.5%) with systolic blood
      pressure averaging at least 20 mm Hg from goal. CONCLUSIONS: Nearly three-fourths
      of adults with CVCs have HTN. Poor control rates of systolic HTN remain a
      principal problem that further compromises their already high cardiovascular
      disease risk.

PMID- 18071165
TI  - Coronary artery calcium scores and risk for cardiovascular events in women
      classified as "low risk" based on Framingham risk score: the multi-ethnic study
      of atherosclerosis (MESA).
AB  - OBJECTIVE: To assess coronary artery calcium (CAC) score and subsequent risk for
      coronary heart disease (CHD) and cardiovascular (CVD) events among asymptomatic
      women judged to be at low risk by the Framingham risk score (FRS), a common
      approach for determining 10-year absolute risk for CHD. Based on population
      survey data, 95% of American women are considered at low risk based on FRS.
      METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) included 3601 women
      aged 45 to 84 years at baseline. The CAC score was measured by coronary computed
      tomography. Cox proportional hazard models were used to examine the CHD and CVD
      risk associated with CAC score among women classified as "low risk" based on FRS.
      RESULTS: Excluding women with diabetes and those older than 79 years, 90% of
      women in MESA (mean +/- SD age, 60 +/- 9 years) were classified as "low risk"
      based on FRS. The prevalence of CAC (CAC score > 0) in this low-risk subset was
      32% (n = 870). Compared with women with no detectable CAC, low-risk women with a
      CAC score greater than 0 were at increased risk for CHD (hazard ratio, 6.5; 95%
      confidence interval, 2.6-16.4) and CVD events (hazard ratio, 5.2; 95% confidence
      interval, 2.5-10.8). In addition, advanced CAC (CAC score > or = 300) was highly
      predictive of future CHD and CVD events compared with women with nondetectable
      CAC and identified a group of low-risk women with a 6.7% and 8.6% absolute CHD
      and CVD risk, respectively, over a 3.75-year period. CONCLUSIONS: The presence of
      CAC in women considered to be at low risk based on FRS was predictive of future
      CHD and CVD events. Advanced CAC identified a subset of low-risk women at higher
      risk based on current risk stratification strategies.

PMID- 18071166
TI  - Trends in tuberculosis/human immunodeficiency virus comorbidity, United States,
      1993-2004.
AB  - BACKGROUND: To our knowledge, this is the first assessment of trends in
      tuberculosis (TB)/human immunodeficiency virus (HIV) comorbidity in the United
      States based on national TB surveillance data. METHODS: We analyzed all incident
      TB cases reported to the Centers for Disease Control and Prevention national TB
      surveillance system from all 50 states and the District of Columbia from 1993
      through 2004. Trends in TB/HIV cases were examined according to selected
      demographic and clinical characteristics. RESULTS: Cases of TB/HIV decreased from
      3681 (15% of 25,108 TB cases) in 1993 to 1187 (8% of 14,515 TB cases) in 2004,
      accounting for 23% of the overall decrease in TB cases during this period. The
      TB/HIV case rate decreased from 1.4/100,000 in 1993 to 0.4/100,000 in 2004. The
      highest TB/HIV comorbidity rates persisted in persons aged 25 to 44 years
      (13.8%), males (9.7%), US-born persons (10.7%), non-Hispanic blacks (17.8%), and
      persons from the Northeast (11.0%) and the South (10.1%). Propensity
      stratification, used to account for the unequal probability of patients with TB
      being tested for HIV during the study period, did not show important differences
      in TB/HIV comorbidity trends. CONCLUSIONS: Comorbidity due to TB/HIV decreased
      substantially between 1993 and 2004, primarily in US-born persons in states that
      experienced a TB resurgence between 1985 and 1992. These decreases coincide with
      improvements in TB control and advances in HIV treatment and diagnosis. The
      overall decreases obscure the wide variation in comorbidity that exists among
      some demographic groups and the recent slowing in the decline over the past 3
      years.

PMID- 18071167
TI  - Physical activity recommendations and decreased risk of mortality.
AB  - BACKGROUND: Whether national physical activity recommendations are related to
      mortality benefit is incompletely understood. METHODS: We prospectively examined
      physical activity guidelines in relation to mortality among 252,925 women and men
      aged 50 to 71 years in the National Institutes of Health-American Association of
      Retired Persons (NIH-AARP) Diet and Health Study. Physical activity was assessed
      using 2 self-administered baseline questionnaires. RESULTS: During 1,265,347
      person-years of follow-up, 7,900 participants died. Compared with being inactive,
      achievement of activity levels that approximate the recommendations for moderate
      activity (at least 30 minutes on most days of the week) or vigorous exercise (at
      least 20 minutes 3 times per week) was associated with a 27% (relative risk [RR],
      0.73; 95% confidence interval [CI], 0.68-0.78) and 32% (RR, 0.68; 95% CI, 0.64
      0.73) decreased mortality risk, respectively. Physical activity reflective of
      meeting both recommendations was related to substantially decreased mortality
      risk overall (RR, 0.50; 95% CI, 0.46-0.54) and in subgroups, including smokers
      (RR, 0.48; 95% CI, 0.44-0.53) and nonsmokers (RR, 0.54; 95% CI, 0.45-0.64),
      normal weight (RR, 0.45; 95% CI, 0.39-0.52) and overweight or obese individuals
      (RR, 0.48; 95% CI, 0.44-0.54), and those with 2 h/d (RR, 0.53; 95% CI, 0.44-0.63)
      and more than 2 h/d of television or video watching (RR, 0.50; 95% CI, 0.45
      0.55). Engaging in physical activity at less than recommended levels was also
      related to reduced mortality risk (RR, 0.81; 95% CI, 0.76-0.86). CONCLUSIONS:
      Following physical activity guidelines is associated with lower risk of death.
      Mortality benefit may also be achieved by engaging in less than recommended
      activity levels.

PMID- 18071168
TI  - Mediterranean dietary pattern and prediction of all-cause mortality in a US
      population: results from the NIH-AARP Diet and Health Study.
AB  - BACKGROUND: The Mediterranean diet has been suggested to play a beneficial role
      for health and longevity. However, to our knowledge, no prospective US study has
      investigated the Mediterranean dietary pattern in relation to mortality. METHODS:
      Study participants included 214,284 men and 166,012 women in the National
      Institutes of Health (NIH)-AARP (formerly known as the American Association of
      Retired Persons) Diet and Health Study. During follow-up for all-cause mortality
      (1995-2005), 27,799 deaths were documented. In the first 5 years of follow-up,
      5,985 cancer deaths and 3,451 cardiovascular disease (CVD) deaths were reported.
      We used a 9-point score to assess conformity with the Mediterranean dietary
      pattern (components included vegetables, legumes, fruits, nuts, whole grains,
      fish, monounsaturated fat-saturated fat ratio, alcohol, and meat). We calculated
      hazard ratios (HRs) and 95% confidence intervals (CIs) using age- and
      multivariate-adjusted Cox models. RESULTS: The Mediterranean diet was associated
      with reduced all-cause and cause-specific mortality. In men, the multivariate HRs
      comparing high to low conformity for all-cause, CVD, and cancer mortality were
      0.79 (95% CI, 0.76-0.83), 0.78 (95% CI, 0.69-0.87), and 0.83 (95% CI, 0.76-0.91),
      respectively. In women, an inverse association was seen with high conformity with
      this pattern: decreased risks that ranged from 12% for cancer mortality to 20%
      for all-cause mortality (P = .04 and P < .001, respectively, for the trend). When
      we restricted our analyses to never smokers, associations were virtually
      unchanged. CONCLUSION: These results provide strong evidence for a beneficial
      effect of higher conformity with the Mediterranean dietary pattern on risk of
      death from all causes, including deaths due to CVD and cancer, in a US
      population.

PMID- 18071170
TI  - Multicenter implementation of a shared graduate medical education resource.
AB  - BACKGROUND: The Accreditation Council of Graduate Medical Education (ACGME) is
      changing residency program assessment to include education outcomes assessment,
      challenging resources of residency training programs. The internet is a means of
      sharing education resources among training programs. METHODS: A multicenter
      survey was distributed to leaders of 80 internal medicine residency training
      programs that shared an online medical knowledge curriculum that included
      education outcomes assessment. Program characteristics, curriculum implementation
      methods, and use of educational outcome assessment were analyzed to determine how
      implementation differed among programs. RESULTS: Seventy-four programs (92%)
      completed the survey. The programs vary in medical school affiliation, number of
      house staff, and proportion of students who specialize on graduation. They most
      commonly use the curriculum to augment a preexisting curriculum (37 programs
      [50%]); 41 programs (56%) use the curriculum to comply with ACGME requirements.
      The programs differ in how they adapt the curriculum to their needs, most
      commonly by discussing modules with house staff (47 programs [63%]). In 61
      programs (82%), module completion is mandatory. Thirty-five programs (47%) use
      penalties to encourage module completion, most commonly poor evaluation scores
      (15 programs [20%]) or withholding of promotion (12 programs [16%]). Nearly all
      programs (71 [97%]) track module completion; 34 programs (47%) track group
      performance on learning objectives; and 8 programs (11%) alter their educational
      curriculum based on group performance. CONCLUSIONS: A medical knowledge
      curriculum that includes education outcome assessment can be adapted at a range
      of residency training programs, helping them to comply with ACGME requirements.
      However, most residency training programs are not using outcomes data to their
      full potential.

PMID- 18071169
TI  - QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized
      trial.
AB  - BACKGROUND: Levomethadyl acetate, methadone hydrochloride, and buprenorphine
      hydrochloride are equally effective treatments for opioid dependence. Each blocks
      the human ether-a-go-go-related gene (hERG)-associated channel in vitro and
      represents a risk for QT prolongation. To compare the effects of 3 known hERG
      associated channel blockers on the corrected QT (QTc), we conducted a randomized,
      controlled trial of opioid-addicted subjects. METHODS: We analyzed 12-lead
      electrocardiograms collected at baseline and every 4 weeks from 165 opioid
      addicted participants in a 17-week randomized double-blind clinical trial of
      equally effective doses of levomethadyl, methadone, and buprenorphine at a major
      referral center. Analyses were limited to the 154 patients with a normal baseline
      QTc = (QT/ radical R-R) who had at least 1 subsequent in-treatment
      electrocardiogram. Patients were randomized to receive treatment with
      levomethadyl, methadone, or buprenorphine (hereinafter, levomethadyl, methadone,
      and buprenorphine groups, respectively). The prespecified end points were a QTc
      greater than 470 milliseconds in men (or >490 milliseconds in women), or an
      increase from baseline in QTc greater than 60 milliseconds. RESULTS: Baseline QTc
      was similar in the 3 groups. The levomethadyl and methadone groups were
      significantly more likely to manifest a QTc greater than 470 or 490 milliseconds
      (28% for the levomethadyl group vs 23% for the methadone group vs 0% for the
      buprenorphine group; P < .001) or an increase from baseline in QTc greater than
      60 milliseconds (21% of the levomethadyl group [odds ratio, 15.8; 95% confidence
      interval, 3.7-67.1] and 12% of the methadone group [odds ratio, 8.4; 95%
      confidence interval, 1.9-36.4]) compared with the buprenorphine group (2% of
      subjects; P < .001). In subjects whose dosage of levomethadyl or methadone
      remained fixed over at least 8 weeks, the QTc continued to increase progressively
      over time (P = .08 for the levomethadyl group, P = .01 for the methadone group).
      CONCLUSION: Buprenorphine is associated with less QTc prolongation than
      levomethadyl or methadone and may be a safe alternative.

PMID- 18071171
TI  - A prognostic risk index for long-term mortality in patients with peripheral
      arterial disease.
AB  - BACKGROUND: Prognostic information in peripheral arterial disease (PAD) may
      provide the basis for optimal management strategies at an early stage. This study
      aimed to develop a prognostic risk index for long-term mortality in patients with
      PAD. METHODS: In a single-center observational cohort study, 2642 patients with
      an ankle-brachial index of 0.90 or lower were randomly divided into derivation (n
      = 1332) and validation (n = 1310) cohorts. Cox regression analysis with stepwise
      backward elimination identified predictors of 1-year, 5-year, and 10-year
      mortality in the derivation cohort. Weighted points were assigned to each
      predictor. Index discrimination was determined in both the derivation and
      validation cohorts. RESULTS: During 10 years of follow-up, 42.2% and 40.4% of
      patients died in the derivation and validation cohorts, respectively. The risk
      index for 10-year mortality (+ points) included renal dysfunction (+12), heart
      failure (+7), ST-segment changes (+5), age greater than 65 years (+5),
      hypercholesterolemia (+5), ankle-brachial index lower than 0.60 (+4), Q-waves
      (+4), diabetes (+3), cerebrovascular disease (+3), and pulmonary disease (+3).
      Statins (-6), aspirin (-4), and beta-blockers (-4) were associated with reduced
      10-year mortality. Patients were stratified into low (<0 points), low
      intermediate (0-5 points), high-intermediate (6-9 points), and high (>9 points)
      risk categories, according to risk score. Ten-year mortality rates were 22.1%,
      32.2%, 45.8%, and 70.4%, respectively (P < .001) and comparable to mortality in
      the validation cohort. C statistics demonstrated good discrimination in both the
      derivation (0.72) and validation cohorts (0.73). CONCLUSIONS: A prognostic risk
      index for long-term mortality stratified patients with PAD into different risk
      categories. This may be useful for risk stratification, patient counseling, and
      medical decision making.

PMID- 18071172
TI  - Association of kidney function and albuminuria with cardiovascular mortality in
      older vs younger individuals: The HUNT II Study.
AB  - BACKGROUND: The cardiovascular risk implications of a combined assessment of
      reduced kidney function and microalbuminuria are unknown. In elderly persons,
      traditional cardiovascular risk factors are less predictive, and measures of end
      organ damage, such as kidney disease, may be needed for improved cardiovascular
      mortality risk stratification. METHODS: The glomerular filtration rate was
      estimated from calibrated serum creatinine, and the urine albumin-creatinine
      ratio (ACR) was measured in 3 urine samples in 9,709 participants of the second
      Nord-Trondelag Health Study (HUNT II), a Norwegian community-based health study,
      followed for 8.3 years with a 71% participation rate. RESULTS: An estimated
      glomerular filtration rate (EGFR) at levels of less than 75 mL/min/1.73 m(2) was
      associated with higher cardiovascular mortality risk, whereas a higher ACR was
      associated with higher risk with no lower limit. Low EGFR and albuminuria were
      synergistic cardiovascular mortality risk factors. Compared with subjects with an
      EGFR greater than 75 mL/min/1.73 m(2) and ACR below the sex-specific median who
      were at the lowest risk, subjects with an EGFR of less than 45 mL/min/1.73 m(2)
      and microalbuminuria had an adjusted incidence rate ratio of 6.7 (95% confidence
      interval, 3.0-15.1; P < .001). The addition of ACR and EGFR improved traditional
      risk models: 39% of subjects with intermediate risk were reclassified to low- or
      high-risk categories with corresponding observed risks that were 3-fold different
      than the original category. Age-stratified analyses showed that EGFR and ACR were
      particularly strong risk factors for persons 70 years or older. CONCLUSIONS:
      Reduced kidney function and microalbuminuria are risk factors for cardiovascular
      death, independent of each other and traditional risk factors. The combined
      variable improved cardiovascular risk stratification at all age levels, but
      particularly in elderly persons where the predictive power of traditional risk
      factors is attenuated.

PMID- 18071173
TI  - Trends in prostate-specific antigen testing from 1995 through 2004.
AB  - BACKGROUND: The utility of the prostate-specific antigen (PSA) test to screen for
      prostate cancer has been widely debated for several years. Whether PSA testing
      rates have changed during this period of controversy is not well known. METHODS:
      We examined the National Ambulatory Medical Care Survey (1995-2004) of visits to
      primary care providers by healthy men aged 35 years or older. We examined visits
      by calendar year and compared the years 2000 through 2004 with the years 1995
      through 1999. We also examined visits by men in the overall population and in
      particular subgroups. RESULTS: Primary care physicians ordered PSA tests in 4.7%
      of all visits in 1995 and in 7.0% of all visits in 2004 (P = .03). In
      multivariate analysis, the odds of a primary care physician ordering a PSA test
      during any clinic visit increased 8% (odds ratio [OR], 1.08; 95% confidence
      interval [CI], 1.04-1.12; P < .001) per year from 1995 through 2004. The increase
      was more pronounced among men making visits for general medical examinations
      (11.2% in 1995 vs 32.3% in 2004; P = .003). Comparing the period 2000-2004 with
      the period 1995-1999, the odds of PSA testing increased in nearly all subgroups
      but most dramatically in black men (OR, 2.3; 95% CI, 1.4-3.8; P = .002) and in
      men 35 through 49 years of age (OR, 1.8; 95% CI, 1.3-2.6; P = .001). CONCLUSION:
      In a nationally representative sample, we found that despite the lack of clear
      evidence of benefit, PSA testing for prostate cancer screening has increased
      dramatically, especially among black men and younger men.

PMID- 18071174
TI  - Range and severity of symptoms over time among older adults with chronic
      obstructive pulmonary disease and heart failure.
AB  - BACKGROUND: Symptoms are a central component of health status; however, little is
      known about the full range and trajectory of symptoms experienced by persons with
      chronic diseases other than cancer. METHODS: Observational cohort study with
      interviews performed at least every 4 months for up to 2 years among community
      dwelling persons 60 years or older with chronic obstructive pulmonary disease
      (COPD) or heart failure (HF). Seven symptoms rated as absent, mild, moderate, or
      severe were assessed at each interview. RESULTS: Among the 79 participants with
      COPD, at least 50% reported shortness of breath, physical discomfort, fatigue,
      and problems with appetite and anxiety. Among the 59 participants with HF, at
      least 50% reported physical discomfort, fatigue, and problems with appetite at
      both their initial and final interviews. Both disease-specific and non-disease
      specific symptoms increased in severity over time. The prevalence of individual
      symptoms did not differ according to whether the participants lived or died.
      CONCLUSIONS: As a potentially modifiable contributor to poor health status, the
      high symptom burden among older persons with COPD and HF represents a large unmet
      need for improved symptom assessment and treatment. This need may not be met by
      current disease management guidelines, which focus on a small number of symptoms
      except for patients at the end of life.

PMID- 18071175
TI  - Communication about chronic critical illness.
AB  - BACKGROUND: Despite poor outcomes, life-sustaining treatments including
      mechanical ventilation are continued for a large and growing population of
      patients with chronic critical illness. This may be owing in part to a lack of
      understanding resulting from inadequate communication between clinicians and
      patients and families. Our objective was to investigate the informational needs
      of patients with chronic critical illness and their families and the extent to
      which these needs are met. METHODS: In this prospective observational study
      conducted at 5 adult intensive care units in a large, university-affiliated
      hospital in New York, New York, 100 patients with chronic critical illness
      (within 3-7 days of elective tracheotomy for prolonged mechanical ventilation) or
      surrogates for incapacitated patients were surveyed using an 18-item
      questionnaire addressing communication about chronic critical illness. Main
      outcome measures included ratings of importance and reports of whether
      information was received about questionnaire items. RESULTS: Among 125
      consecutive, eligible patients, 100 (80%) were enrolled; questionnaire
      respondents included 2 patients and 98 surrogates. For all items, more than 78%
      of respondents rated the information as important for decision making (>98% for
      16 of 18 items). Respondents reported receiving no information for a mean (SD) of
      9.0 (3.3) of 18 items, with 95% of respondents reporting not receiving
      information for approximately one-quarter of the items. Of the subjects rating
      the item as important, 77 of 96 (80%) and 69 of 74 (93%) reported receiving no
      information about expected functional status at hospital discharge and prognosis
      for 1-year survival, respectively. CONCLUSIONS: Many patients and their families
      may lack important information for decision making about continuation of
      treatment in the chronic phase of critical illness. Strategies for effective
      communication in this clinical context should be investigated and implemented.

PMID- 18071176
TI  - Secondhand smoke and health-related quality of life in never smokers: results
      from the SAPALDIA cohort study 2.
AB  - BACKGROUND: Although secondhand smoke (SHS) has been linked with various
      respiratory conditions and symptoms, its association with health-related quality
      of life (HRQOL) is unknown. METHODS: A cross-sectional study was performed of
      2500 never smokers in Switzerland who participated in the Swiss Cohort Study on
      Air Pollution and Lung Diseases in Adults and completed a 36-Item Short Form
      Health Survey (SF-36) in 2002. Using linear regression models adjusting for
      confounders, we measured the association between HRQOL and moderate or high SHS
      exposure (< or =3 h/d or >3 h/d) compared with no SHS exposure. Data from men and
      women were analyzed separately and further stratified by source of SHS (home,
      workplace, and public spaces). RESULTS: After adjustments, SHS was associated
      with reduced scores in all SF-36 domains. High SHS exposure predicted a greater
      reduction in HRQOL. Compared with nonexposed women, those with high SHS exposure
      at home had significantly lower scores on the physical functioning (-7.8, P <
      .001), role physical (-10.5, P = .02), bodily pain (-9.2, P = .01), and social
      functioning (-8.1, P = .007) domains. Exposed men had lower scores for the role
      physical domain (-20.0, P < .001) and a trend toward lower scores in other
      domains. In women, exposure to SHS at home was associated with a stronger
      negative effect on HRQOL than at work and in public spaces. CONCLUSIONS:
      Secondhand smoke is associated with reduced HRQOL, more significantly so in
      women. Exposure to SHS at home and high levels of exposure are associated with
      lower SF-36 scores, suggesting a dose-response relationship.

PMID- 18071177
TI  - The trap: professional exposure to human immunodeficiency virus antibody negative
      blood with high viral load.

PMID- 18071178
TI  - How can obesity be healthy?

PMID- 18071179
TI  - High recurrence rate of CA-MRSA skin and soft tissue infections.

PMID- 18071180
TI  - Validation of a simple clinical diabetes prediction model in a middle-aged,
      white, German population.

PMID- 18071181
TI  - The effect of obesity on disability vs mortality in older american: the potential
      implication of testosterone.

PMID- 18071182
TI  - Improving appropriateness of prostate-specific antigen screening.

PMID- 18071183
TI  - Selenium and HIV-1: hope or hype?

PMID- 18071184
TI  - Palpable pulse delay in subclavian steal.

PMID- 18071185
TI  - Clarification of study and citation.

PMID- 18071186
TI  - Vitamin D intake and breast cancer risk in postmenopausal women.

PMID- 18071188
TI  - Predictors of tamoxifen discontinuation among older women with estrogen receptor
      positive breast cancer.
AB  - PURPOSE: Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) 
      positive breast cancer is more effective than 2 years of use. However,
      information on tamoxifen discontinuation is scanty. We sought to identify
      predictors of tamoxifen discontinuation among older women with breast cancer.
      PATIENTS AND METHODS: Within six health care delivery systems, we identified
      women >or= 65 years old diagnosed with stage I to IIB ER-positive or
      indeterminant breast cancer between 1990 and 1994 who had filled a prescription
      for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen
      prescription. We used automated pharmacy records to validate tamoxifen
      prescription information abstracted from medical records. The primary end point
      was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen
      during 5 years of follow-up. We used Cox proportional hazards to identify
      predictors of tamoxifen discontinuation. RESULTS: Of 961 women who were
      prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5
      years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70
      years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged >or= 80 years (HR
      = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at
      3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the
      number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to
      2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI,
      1.00 to 1.85), and have received breast-conserving surgery (BCS) without
      radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). CONCLUSION:
      Attention to nonadherence among older women at risk of discontinuation,
      particularly those receiving BCS without radiotherapy, might improve breast
      cancer outcomes for these women.

PMID- 18071189
TI  - Protein targets of oxidized phospholipids in endothelial cells.
AB  - Oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine
      (Ox-PAPC) are found in atherosclerotic lesions, apoptotic cells, and oxidized LDL
      and stimulate human aortic endothelial cells (HAECs) to produce inflammatory
      cytokines, leukocyte chemoattractants, and coagulation factors. This regulation
      is thought to be a receptor-mediated process in which oxidized phospholipids
      activate specific receptors on HAECs to evoke an inflammatory response. To
      characterize the HAEC proteins with which oxidized phospholipids interact, a
      biotinylated PAPC analog, 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidyl-(N
      biotinylethanolamine) (PAPE-N-biotin), was synthesized. Oxidation of PAPE-N
      biotin in air generated a mixture of biotin-labeled oxidized lipids analogous to
      Ox-PAPC. Ox-PAPE-N-biotin, like Ox-PAPC, induced interleukin-8 (IL-8) protein
      synthesis and stimulated IL-8, low density lipoprotein receptor, heme oxygenase
      1, and activating transcription factor-3 mRNA expression in HAECs. After
      treatment of HAECs with Ox-PAPE-N-biotin, the cellular proteins were isolated and
      separated by SDS-PAGE. Western analysis with streptavidin-HRP demonstrated at
      least 20 different biotinylated HAEC proteins to which the Ox-PAPE-N-biotin was
      associated, which were not detected with unoxidized PAPE-N-biotin treatment. This
      work suggests that oxidized phospholipids, such as those found in oxidized LDL,
      apoptotic cells, and atherosclerotic lesions, form tight interactions with
      specific endothelial cell proteins, which may be responsible for the inflammatory
      response. Identification of these putative oxidized phospholipid targets may
      reveal therapeutic targets to modulate inflammation and atherosclerosis.

PMID- 18071190
TI  - Melatonin pharmacokinetics in premenopausal and postmenopausal healthy female
      volunteers.

PMID- 18071191
TI  - Pharmacokinetic profiles of controlled-release hydrogel polymer vaginal inserts
      containing misoprostol.
AB  - Misoprostol, a prostaglandin E1 analogue, is commonly administered intravaginally
      for cervical ripening and induction of labor. There is uncertainty regarding the
      correct dose because of the need to divide the tablets, and there is difficulty
      in removing the product when there is an adverse event. A proprietary hydrogel
      polymer containing a removable controlled-release reservoir dose of misoprostol
      is being developed for vaginal administration (misoprostol vaginal insert) to
      address these drawbacks while maintaining efficacy. This study investigated the
      pharmacokinetic profiles of these vaginal inserts and orally administered
      misoprostol. Twelve nonpregnant women received 100-, 200-, and 400-microg
      misoprostol vaginal inserts and separately received an oral dose of 200 microg of
      misoprostol. Values for area under the plasma concentration versus time curve,
      from time 0 to the last measurable concentration, were dose proportional with
      481, 1026, and 2191 pg.h/mL for the 100-, 200-, and 400-microg misoprostol
      vaginal inserts, respectively. Maximum plasma concentrations were 33.1, 73.4, and
      144 pg/mL for the 100-, 200-, and 400-microg misoprostol vaginal inserts,
      compared with 609 pg/mL for the 200 microg of oral misoprostol. After
      administration of the insert, plasma misoprostol acid levels increased gradually
      with time of the maximum measured plasma concentration at 5 to 9 hours. Following
      removal of the insert, misoprostol acid was eliminated rapidly from the systemic
      circulation with a mean half-life <1 hour.

PMID- 18071192
TI  - Does lower-extremity arterial disease predict future falling among older men and
      women?
AB  - The purpose of this study was to determine whether lower-extremity peripheral
      arterial disease (PAD) is an independent risk factor for falls among older
      persons. Men and women 55 years old and older participated. Subjects with PAD (n
      = 86) were identified from a noninvasive vascular laboratory and a general
      medicine practice. Randomly selected controls without PAD (n = 82) were
      identified from the same medicine practice. Subjects were categorized into PAD
      (ankle brachial index, <0.90) or controls (ankle brachial index, 0.90 to 1.50).
      Subjects underwent a comprehensive baseline evaluation for fall risk. Prospective
      fall data were obtained using monthly mail-in postcards and structured telephone
      interviews over a mean follow-up of 9.6 +/- 2.9 months. Two independent
      investigators blinded to PAD status reviewed each fall incident for its
      eligibility. A total of 37 subjects (22%) had at least 1 eligible fall. In an
      unadjusted Cox regression model, the relative risk of falling was lower among PAD
      subjects than among controls (relative risk, 0.54; 95% confidence interval, 0.28
      to 1.06). After adjustment for age, gender, history of frequent falls in the last
      year, number of comorbidities, and balance and gait abnormalities, PAD was
      significantly associated with a lower risk of falling (relative risk, 0.43; 95%
      confidence interval, 0.21 to 0.87) as compared with controls. PAD is associated
      with a lower risk of falling as compared with persons without PAD among older men
      and women. Future study is needed to determine whether reduced levels of physical
      activity among patients with PAD account for the lower rate of falling observed
      here.

PMID- 18071193
TI  - The use of positron emission tomography with (18)F-fluorodeoxyglucose for the
      diagnosis of vascular graft infection.
AB  - Vascular graft infection is associated with a high morbidity and mortality rate.
      Diagnosis is difficult, as there is no single diagnostic criterion that has a
      100% accuracy. A combination of physical examination, laboratory tests, and
      several imaging techniques is mandatory. Beside a wide range of indications in
      the oncological field, positron emission tomography with (18)F-fluorodeoxyglucose
      (FDG-PET) has a well-known role in the diagnosis of bone and soft-tissue
      infections. Some authors have recently reported on the potential use of FDG-PET
      in the diagnosis of vascular graft infections. The aim of this study is to review
      personal experience. Five consecutive patients with a suspected prosthetic
      infection (1 aortobifemoral bypass, 3 femoropopliteal bypasses, and 1
      femorofemoral bypass) underwent FDG-PET. All prostheses showed a moderate or
      intense FDG tracer uptake. All 3 patients with an intense FDG uptake proved to
      have a prosthetic infection (based on microbiologic examination). These
      preliminary results suggest that FDG-PET might be an interesting tool to confirm
      vascular graft infection.

PMID- 18071194
TI  - Diabetes and endometrial cancer: an evaluation of the modifying effects of other
      known risk factors.
AB  - To determine whether risk of endometrial cancer among women with type 2 diabetes
      differs with respect to other endometrial cancer risk factors, the authors used
      data from a population-based case-control study (1,303 cases and 1,779 controls)
      conducted in western Washington State during 1985-1999. History of type 2
      diabetes was associated with endometrial cancer (odds ratio (OR) = 1.7, 95%
      confidence interval (CI): 1.2, 2.3), more strongly among women with a recent
      diabetes diagnosis (<5 years) (OR = 2.6, CI: 1.5, 4.7) than among those with a
      more distant diagnosis (> or =5 years) (OR = 1.3, CI: 0.8, 1.9). Type 2 diabetes
      was associated with endometrial cancer among women with a body mass index (BMI)
      (weight (kg)/height (m)(2)) less than 35 but not among women with a BMI of 35 or
      more. The observed associations persisted after finer adjustment for BMI to
      control for residual confounding. History of diabetes was associated with a
      twofold increased risk of endometrial cancer among hypertensive women, but no
      association was observed among nonhypertensive women. The risk associated with
      type 2 diabetes appeared not to vary greatly with respect to other endometrial
      cancer risk factors. These results support the hypothesis that type 2 diabetes is
      associated with endometrial cancer irrespective of the presence of other risk
      factors for this disease, except possibly hypertension and extreme obesity.

PMID- 18071196
TI  - Masculinity/femininity of fine fragrances affects color-odor correspondences: a
      case for cognitions influencing cross-modal correspondences.
AB  - Four experiments found that the colors people choose as corresponding to the
      odors of fine fragrances are influenced by the perceived masculinity/femininity
      of those fragrances. Experiment 1 examined the colors chosen for 3 male and 3
      female fragrances. The pattern of colors chosen for female fragrances differed
      from that for male fragrances. Experiments 2 and 3 found that colors assigned to
      2 unisex fragrances depend on whether subjects thought that the fragrances were
      male or female fragrances. Experiment 4, by labeling unisex fragrances as male or
      female, showed that this difference in color selection was the result of
      subjects' thinking that a fragrance is a male or female fragrance. Thinking of
      the masculinity/femininity of a fragrance influences the selection of colors that
      corresponds to these odors.

PMID- 18071195
TI  - The central sulcus: an observer-independent characterization of sulcal landmarks
      and depth asymmetry.
AB  - Studies of the central sulcus (CS) often use observer-dependent procedures to
      assess CS morphology and sulcal landmarks. Here, we applied a novel method
      combining automated sulcus reconstruction, surface parameterization, and an
      observer-independent depth measurement to study the CS. This facilitated the
      quantitative assessment of the spatial position and intersubject variability of
      several sulcal landmarks. Sulcal depth profiles also allowed us to develop an
      algorithm for the clear identification of several landmarks, including the pli de
      passage fronto-parietal moyen (PPFM), first described by Broca. Using this
      algorithm, the PPFM was identified in the majority of sulci, but exhibited
      limited spatial variability. This appears to support Cunningham's theory that
      this landmark may be a developmental remnant, and may argue against its role as a
      guide to the more variable somatotopic hand area. Sulcal depth profiles were also
      utilized to assess the influence of sex, handedness, and age on CS morphology.
      These profiles revealed leftward depth asymmetry in the superior extent of the CS
      of male subjects and near the midpoint of the CS in female subjects. Age
      correlations were performed for these asymmetries, and a significant correlation
      was seen only in the male subgroup.

PMID- 18071197
TI  - Perceptual processing strategy and exposure influence the perception of odor
      mixtures.
AB  - In flavor perception, both experience with the components of odor/taste mixtures
      and the cognitive strategy used to examine the interactions between the
      components influence the overall mixture perception. However, the effect of these
      factors on odor mixtures perception has never been studied. The present study
      aimed at evaluating whether 1) previous exposure to the odorants included in a
      mixture or 2) the synthetic or analytic strategy engaged during odorants mixture
      evaluation determines odor representation. Blending mixtures, in which subjects
      perceived a unique quality distinct from those of components, were chosen in
      order to induce a priori synthetic perception. In the first part, we checked
      whether the chosen mixtures presented blending properties for our subjects. In
      the second part, 3 groups of participants were either exposed to the odorants
      contributing to blending mixtures with a "pineapple" or a "red cordial" odor or
      nonexposed. In a following task, half of each group was assigned to a synthetic
      or an analytical task. The synthetic task consisted of rating how typical (i.e.,
      representative) of the target odor name (pineapple or red cordial) were the
      mixtures and each of their components. The analytical task consisted of
      evaluating these stimuli on several scales labeled with the target odor name and
      odor descriptors of the components. Previous exposure to mixture components was
      found to decrease mixture typicality but only for the pineapple blending mixture.
      Likewise, subjects engaged in an analytical task rated both blending mixtures as
      less typical than did subjects engaged in a synthetic task. This study supports a
      conclusion that odor mixtures can be perceived either analytically or
      synthetically according to the cognitive strategy engaged.

PMID- 18071198
TI  - Evidence in favor of a role of idiotypic network in autoimmune hemolytic anemia
      induction: theoretical and experimental studies.
AB  - Formation dynamics of antibodies to rat erythrocytes (REs) and auto-antibodies to
      mouse erythrocytes were studied in an experimental model of autoimmune hemolytic
      anemia (AHA) in mice. The experimental conditions of AHA were simulated in a
      mathematical model of an immune network. It was found that maximal production of
      auto-antibodies and antibodies to REs do not synchronize. Antiserum, obtained at
      the peak of auto-antibodies formation, competed with REs for bounding with
      antibodies. This represents proof that auto-antibodies to erythrocytes and
      antibodies to REs are an idiotype-anti-idiotypic pair. In the autoimmune
      reaction, the autoreactive clone, being anti-idiotypic, responded earlier than
      the clone reacting to the injected antigen. Comparison of autoimmune reaction
      kinetics in the mathematical model of an immune network with experimental
      dynamics of AHA shows them to be similar. So activation of the autoreactive clone
      to erythrocytes during experimental AHA in mice is mediated by idiotype-anti
      idiotypic interactions with the clone reacting to REs.

PMID- 18071199
TI  - Selective sweeps in a 2-locus model for sex-ratio meiotic drive in Drosophila
      simulans.
AB  - A way to identify loci subject to positive selection is to detect the signature
      of selective sweeps in given chromosomal regions. It is revealed by the departure
      of DNA polymorphism patterns from the neutral equilibrium predicted by coalescent
      theory. We surveyed DNA sequence variation in a region formerly identified as
      causing "sex-ratio" meiotic drive in Drosophila simulans. We found evidence that
      this system evolved by positive selection at 2 neighboring loci, which thus
      appear to be required simultaneously for meiotic drive to occur. The 2 regions
      are approximately 150-kb distant, corresponding to a genetic distance of 0.1 cM.
      The presumably large transmission advantage of chromosomes carrying meiotic drive
      alleles at both loci has not erased the individual signature of selection at each
      locus. This chromosome fragment combines a high level of linkage disequilibrium
      between the 2 critical regions with a high recombination rate. As a result, 2
      characteristic traits of selective sweeps--the reduction of variation and the
      departure from selective neutrality in haplotype tests--show a bimodal pattern.
      Linkage disequilibrium level indicates that, in the natural population from
      Madagascar used in this study, the selective sweep may be as recent as 100 years.

PMID- 18071200
TI  - Telomeres and longevity: testing an evolutionary hypothesis.
AB  - Identifying mechanisms that underlie variation in adult survivorship provide
      insight into the evolution of life history strategies and phenotypic variation in
      longevity. There is accumulating evidence that shortening telomeres, the
      protective caps at the ends of chromosomes, play an important role in individual
      variation in longevity. Given that telomeres generally shorten with age, it was
      surprising to find that in a population of a long-lived seabird, Leach's storm
      petrel, telomeres appear to lengthen with age. This unique finding suggested that
      the longest lived individuals are able to elongate telomeres, an interpretation
      we call the "elongation hypothesis." Alternatively, the "selection hypothesis"
      states that the longest lived individuals start with the longest telomeres and
      variation in telomere length decreases with age due to the selective
      disappearance of individuals with short telomeres. In the same population in
      which evidence supporting both hypotheses was uncovered, we tested mutually
      exclusive predictions from the elongation and selection hypotheses by measuring
      telomere length with the telomere restriction fragment assay in hatchling and
      old, adult storm petrels. As previously found, adult birds had longer telomeres
      on average compared with hatchlings. We also found that 3 hatchlings had mean
      telomere lengths exceeding that of the most extreme old bird, old birds on
      average had longer initial telomere lengths than hatchlings, and the variance in
      mean telomere length was significantly greater for hatchlings than for old birds,
      all predicted by the selection hypothesis. Perhaps more surprisingly, the oldest
      adults also show little or no accumulation of short telomeres over time, a
      pattern unknown in other species. Long telomeres are thought to provide a buffer
      against cellular senescence and be generally indicative of genome stability and
      overall cell health. In storm petrels, because the progressive accumulation of
      short telomeres appears negligible, variation in telomere length at birth may be
      linked to individual variation in longevity.

PMID- 18071201
TI  - Perceived job demands relate to self-reported health complaints.
AB  - BACKGROUND: Illness and illness behaviour are important problems in the Dutch
      workforce. Illness has been associated with job demands, with high demands
      relating to poorer health. It has not been reported whether subjective health
      complaints relate to job demands. AIMS: To investigate whether perceived
      (physical and mental) workload and specific job demands are associated with self
      reported health complaints. METHODS: Cross-sectional study of a random sample of
      983 male employees working in manufacturing industry. Job demands and health
      complaints were investigated using the self-completed Basic Occupational Health
      Questionnaire. The relationship between demands and health complaints were
      studied using logistic regression analysis with health complaints as the outcome
      variable. RESULTS: The questionnaires of 867 workers (88%) were suitable for
      analysis. The prevalence of health complaints was high. Physical workload was
      related to musculoskeletal symptoms. Standing work predicted pain in the legs and
      thoracic as well as low back pain, while sedentary work predicted low back pain.
      Heavy lifting predicted low back pain and pain in the extremities. Regular
      bending predicted low back pain and pain in the legs. Repetitive movements
      predicted pain in the arms and thoracic as well as low back pain. Mental workload
      was associated with fatigue and chest pain. Working under time pressure and
      working behind schedule were not related to self-reported health complaints.
      CONCLUSIONS: Perceived physical job demands matched with self-reported
      musculoskeletal complaints, whereas perceived mental job demands were unrelated
      to specific complaints.

PMID- 18071202
TI  - The use of personal protective equipment in pregnant greenhouse workers.
AB  - AIM: To determine the use of personal protective equipment (PPE) among pregnant
      greenhouse workers in Italy and to identify risk factors related to the non-use
      of appropriate preventive measures. METHODS: A structured questionnaire was
      administered by trained interviewers, to Italian female greenhouse workers
      regarding their use of PPE and the occurrence of adverse pregnancy outcomes in
      their first pregnancy. RESULTS: Two hundred and thirty-two workers participated.
      Although most pregnant women used at least one form of PPE while working, there
      were differences in PPE use in different social groups. Overall, the protection
      was inadequate in the south of Italy and among the less educated. Pregnant women
      performing the most dangerous jobs often did so without using PPE. Even the use
      of gloves was absent in 50% of pregnant women who during their pregnancy prepared
      and mixed pesticides, and among 38% of those who applied pesticides directly.
      CONCLUSIONS: The use of protective measures was inadequate in the south of Italy
      and among less educated women. The study indicates the need for urgent
      interventions aimed at improving PPE use during pregnancy.

PMID- 18071203
TI  - [Early compensation for the loss of bile during external drainage].
AB  - The article presents the results of treatment of mechanical jaundice; 115
      patients with mechanical jaundice were treated by Choledochotomy; in 92 cases
      external drainage after Choledochotomy was employed. It was found that early and
      adequate decompression of gall ducts decreases postoperative complications. The
      investigation showed that the frequency of early post-operative complications are
      directly connected with daily external bile loss in patients with external
      drainage of gall ducts. Early return of bile into duodenum increases motor
      activity of duodenum, to early recovery of intestines peristaltic, to decrease of
      acid production by stomach and eliminates some of homeostasis disorders.

PMID- 18071204
TI  - [Preparation for the surgery and surgical treatment for complicated abdominal
      hernias].
AB  - The analysis of surgical treatment of 98 patients with complicated ventral
      hernias showed that in preparation for the surgery should be conducted ultrasound
      investigation, thorough preparation for surgery with dynamic pneumatic
      compression, as well as measures to avoid purulent inflammatory complications
      during the surgery and post operation period, improves the outcome of treatment
      of ventral hernia.

PMID- 18071205
TI  - Combined endoscopic upper-mid face lift and short-scar cervicofacial
      rhytidoplasty principes in different aging group patients.
AB  - Endoscopically assisted face lift procedures revealed necessity of additional
      procedures to achieve best aesthetic results with minimal trauma and shortest
      rehabilitation period in middle aged patients. To get more effective and stabile
      results combination of different types of rhytidectomy was performed as an
      addition to usual methods. In years 2005 - 2007 in the plastic surgery clinic
      "Caraps Medline" endoscopically assisted subperiosteal face lift was performed on
      25 patients; combined procedures were performed on 22 patients. Combined
      procedures included endoscopic face lift and short-scar cervicofacial
      rhytidoplasty which contained upper and mid endoscopically assisted lift and
      inferior face and traditional SMAS plastic elements with or without neck plastic.
      Patients were divided into 3 groups. The first group - 25-38 years old (20
      patients), the second group - 39-50 years old (10 patients) and the third group -
      over 50 years old (7 patients). The observation period from the treatment ending
      was from 2 to 26 months. All patients were satisfied with the results.
      Endoscopically assisted face lift is recommended for 25-38 year old patients. For
      patients ranging from 39 to 50 years old a combined procedure of subperiosteal
      ednoscopically assisted rhytidectomy is recommended. For patients over 50 years
      old it's necessary to prolong the incision to retro auricular region and hair
      line with blepharoplasty. In all aging groups, depending on skin condition,
      elasticity and derma thickness neck and cheeks liposuction and immediate
      postoperative chemo peel is recommended.

PMID- 18071206
TI  - [The effect of delivery method on perinatal outcomes in case of absense of end
      diastolic blood flow in fetal umbilical artery].
AB  - The aim of the research was to evaluate the effect of delivery methods on
      perinatal outcomes in case of absent end-diastolic flow in the umbilical artery.
      Prospective observational was carried out on 58 pregnant women of whom 32 women
      delivered via Caesarian operation, 26 women - via vaginal birth. The research
      included pregnancy termination study: intranatal mortality rate, perinatal
      mortality rate, Low Apgar Score at birth, newborn admission to intensive care
      unit. Intranatal mortality rate in women delivered via vaginal birth was 19%;
      perinatal mortality rate was twice lower in Caesarian operation group compared
      with that of vaginal birth group. The number of newborns who were admitted to the
      newborn intensive care unit was 4, 4 times higher in vaginal birth group vs.
      Caesarian operation group. There was invert correlation between Caesarian
      operation rate and perinatal mortality rate with absent end diastolic flow in the
      umbilical artery. Absent end-diastolic flow in the umbilical arteries or in the
      aorta of fetus is characterized by increased perinatal mortality and morbidity.
      In case of absent end-diastolic flow in the umbilical artery Caesarian operation
      is recommended to decrease perinatal mortality.

PMID- 18071208
TI  - About mechanisms of multiple cancer development.
AB  - The article discusses the possible pathogenic mechanisms of breast and thyroid
      malignancy as simultaneously developed diseases. The goal of this article was to
      reveal the frequency of breast cancer among patients with thyroid malignancy; to
      study the role of thyroid disorders in development of breast cancer; to determine
      the effectiveness of conservative medical management of thyroid gland after
      radical surgical treatment of thyroid cancer in prevention of breast cancer.
      Interaction of breast and thyroid malignancy was studied. As the first stage of
      scientific investigation the frequency of breast cancer among the patients having
      thyroid gland malignancy was analyzed; the role of disorders occurred during it
      in triggering breast cancer was identified; the effectiveness of medical
      management after radical surgical treatment of thyroid malignancy in preventing
      breast cancer was determined. Specific hormonal indices and markers of breast
      cancer among the patients having thyroid gland malignancy were determined.
      Ultrasound and cytological examinations were performed. The possibilities of
      prevention breast or thyroid malignancy development were studied. Algorithm of
      diagnosis and treatment of breast cancer in patients with thyroid malignancy were
      created through systematization of interconnections between both pathologies.

PMID- 18071207
TI  - [State of the hypothalamo-hypophyseal-ovarian system in young nullipara women
      with ectopia of the cervix of uterus during taking the hormonal contraceptives].
AB  - Background diseases of the cervix of the uterus play one of the leading roles in
      the structure of gynecological pathology and present the risk of the development
      precancerous changes. Ectopia is observed in the structure of precancerous
      processes of the cervix of the uterus in 38, 8% of women and in 42, 2% cases of
      gynecological diseases. Our aim is to investigate the content of gonadotropic and
      steroid hormones in the blood plasma of young nullipara women with different
      types of ectopia during taking hormonal contraceptives. Cohort study has been
      carried out by using simple blind method. The quantitative data analyses were
      performed using the Statistical Package for the Social Sciences (SPSS) in order
      to reveal the correlation between taking of oral hormonal contraceptives and the
      hormone content in the blood plasma among young nullipara women with different
      types of ectopia. Descriptive statistics were calculated for all the study
      variables. The results displayed correlation between taking the oral hormonal
      contraceptives and changes of hormonal background in young women with ectopia of
      the cervix of the uterus during taking hormonal contraceptives. The study show
      that the secretions of gonadotropic hormone and ovary hormone peculiarities
      depend on the type of ectopia of the cervix of the uterus. The effect of hormonal
      contraception on cervix of the uterus of young nullipara women with ectopia was
      investigated. The oral contraceptive, Exluton is recommended in young nullipara
      women with ectopia.

PMID- 18071209
TI  - [Complex treatment of mastopathy patients with concomitant diseases].
AB  - Efficiency value of complex treatment of patients with cystic disease during side
      illnesses. The aim of the article was to study the efficiency of complex
      treatment of mastopitia patients with concomitant diseases. The complex therapy
      of 1044 patients was carried out. Patients with cystic disease who does not
      suffer concomitant diseases (152 patients) where treated with mastodinon,
      vitamins, ginsheng, dehidratation, trancvilizators, antihistamines, drugs of K.
      After 24-26 months of treatment 144 (95%) patients fully recovered. The
      subjective progress was found in 8 cases (4%). In group with hormonal disorders
      recovery was in 120 cases (90%) and the subjective progress was in 13 patients
      (6%). Apart, the hormonal drugs had been used considering hormonal profile. 401
      patients with concomitant diseases of genitals were treated with hormones,
      iodinotherapy and mastodinon. The best result in this group has been shown in
      patients with uterus fibromiomas - 110 patients and with ovarian micro cists with
      no need of surgical treatment - 78 patients compared with chronic adneqsitis (213
      patients) - 90 (82%) patients; 67 (86%) patients; 162 (76%) patients. In case of
      concomitant diseases of liver and gold bladder, the treatment was effective in
      113 (89%) patients. Ineffective treatment has been discovered in 5% 6 (5%)
      patients with hepatopathia and 28 (22%) patients with cholecistitis. The L
      thyroxin was included in treatment in case of hypothyreosis (66 patients).
      Positive effect has been reached in 52 (78,5%) patients and progressive recovery
      was found in 13 (20%) patients. The complex therapy was effective for 648 (62%)
      of 1044 patients. Positive development was in 238 (27,8%) cases. In the group of
      patients who did not suffer concomitant diseases 4,9% has shown progress in
      treatment and 92,6% fully recovered.

PMID- 18071210
TI  - [Immunological aspects of aphthous stomatitis].
AB  - The purpose of the present work was to study the role of cellular and humoral
      immunity in patients with aphthous stomatitis. The research was conducted at
      Tbilisi Hospital for War Veterans. Immunologic parameters of 61 patients aged
      from 15 to 60 years old were analyzed. The statistical data processing included
      calculation of average arithmetic values and their standard deviations.
      Parameters of the immune status of the patients during exacerbation and under
      treatment were investigated. It was revealed that during exacerbation of
      stomatitis the quantity of CD3, CD4, cytophagous activity, and NK were
      diminished. Indices of CD8, CD72, and IgA, were within the norm. Indices of IgM,
      IgG, IgE, parameter of IL-6, antimicrobial and antitoxic antibody titer were
      increased. After treatment increase and approach to standard CD3, CD4, NK, and
      parameters of phagocytosis. IgG, IgM and antitoxic antibody titer decrease and
      approach to standard. During exacerbation of recurrent aphthous stomatitis the
      immune status of the human decrease, this is restored after treatment.

PMID- 18071212
TI  - [Relation of serum uric acid levels with basic metabolic parameters in patients
      with metabolic syndrome during insulin-sensitizing therapy].
AB  - The aim of our investigation was to study the peculiarities of serum uric acid
      (UA) levels in patients with metabolic syndrome (MS) during 6 month therapy with
      metformin (MF), Rosiglitazone (RG) and their combination. 30 patients with MS (10
      males, 20 females, mean age - 35,5+/-9,7 years) have been investigated by all
      parameters of MS and serum UA levels. Investigated group was divided into 3
      subgroups of 10 patients: group 1 - patients on RG; group 2 - patients on MF;
      group 3 - patients on RG + 850-1000 mg of MF. Results of investigation showed
      that UA serum levels did not decrease significantly. However, the frequency of
      hyperuricemia decreased significantly. PPG, basal C-peptide, and HOMA-% IR also
      decreased significantly. Despite percentage reduction of BMI in group 3 (7,6%),
      decrease of UA and HOMA-IR was significantly higher in group 1 (18,2% and 37.0%,
      respectively). Correlation analysis showed that decrease of UA significantly
      correlated with BMI and HOMA-IR in the whole group (r=0.5674, p=0.001; r=0.5437,
      p=0.002; respectively); in group 1 - with HOMA-IR (r=0.5753, p=0.016); in group 3
      - with BMI (r=0.7821, p<0.001). Obtained results showed that UA levels and
      hyperuricemia cases significantly decreased during insulin sensitizing therapy.

PMID- 18071211
TI  - Systemic inflammatory responses in patients with acute otitis media and the
      impact of treatment with sinupret.
AB  - The systemic inflammatory responses and the impact of sinupret therapy have been
      investigated in 14 patients with acute otitis media, AOM. The age of inspected
      individuals covered a range of 29.0+/-12.3 years. The blood samples were taken at
      the admission and after ten days treatment with sinupret. The dosage of sinupret
      application was two tablets or 50 drops three times per day. Utilizing the
      technique of enzymelinked immunoassays, the concentrations of two cytokines, TNF
      alpha and IL-6, were measured in the blood serum. The minimum detectable amount
      of cytokines was less then 2.5 pg/ml. Age-matched five healthy subjects without
      significant medical history served for controls. The study proved an existence of
      systemic inflammatory responses under the AOM. In AOM patients as compared with
      healthy individuals the concentrations of both cytokines were elevated, although
      the difference reached the statistically significant level with respect to TNF
      alpha but not to IL-6. After treatment with sinupret, the TNF-alpha level dropped
      noticeably, proving a recovery from the pathology. IL-6 displayed a similar
      pattern, although the difference between pre- and post-treatment samples was
      statistically nonsignificant. Assessment of varies cytokines and proper
      establishment of their profiles could detect more specific marker(s) of AOM of
      both bacterial or viral etiology and could promote thus a precise prediction of
      the outcome of the pathology. Generally, the estimation of cytokines under AOM
      could offer a powerful tool for the objective evaluation of efficacy of treatment
      and for the avoidance of the ineffective drug therapy.

PMID- 18071213
TI  - [Immune system of splenectomized thalassemia patients in different periods after
      splenectomy].
AB  - Thalassemia is a heterogeneous group of inherited disorders. The genetic defect
      results in reduced rate of synthesis of one of the globin chains that make up
      hemoglobin. Reduced synthesis of one of the globin chains causes the formation of
      abnormal hemoglobin molecules, and this in turn causes the anemia which is the
      symptom of the thalassemias. There are several forms of thalassemia. Thalassemias
      are classified according to which chain of the hemoglobin molecule is affected.
      The severity of the thalassemias is correlated with the number of affected globin
      loci: the greater the number of affected loci, the more severe will be the
      manifestations of the disease. Many of the thalassemia patients need splenectomy.
      The efficiency of splenectomy is not well studied. The research was conducted to
      study humoral and cellular immunity of 30 Thalassemia intermedia patients and 15
      patients with Hemoglobin H disease in different periods after splenectomy. The
      functional activity of segmented neutrophil parameters before operation was low;
      in the second day and during a month after operation parameters gradually
      decreased; and in the remote terms after splenectomy. By first year after
      operation the same parameters have increased up to an initial level.

PMID- 18071214
TI  - [Composite herbal medicine paradon--modulator of apoptosis induced by nitrogen
      oxygen stress].
AB  - Apoptosis is a mechanism that regulates the quantity and the quality of cells and
      provides the maintenance of body homeostasis. Disregularion of apoptosis may
      result in severe diseases. In this regard there is an urgent need in medicine,
      which modulates apoptosis. The purpose of the present research was to study the
      effect of composite herbal medicine Paradon on the intensity of apoptosis induced
      by nitrogen-oxygen stress. The research has been conducted on the intensively
      proliferating leukemia - transformed T cells (Jurkat cells). Medicinal
      preparation Paradon revealed proliferative - stimulating effect, antioxidant
      effect on Jurkat cells, incubated with oxygen and nitrogen free radical donors
      (hydrogen peroxide (Sigma) and sodium nitroprusside (Naniprus, Sopharma)).
      Paradon - through the recovery of energoproducing system activity reduces the
      intensity of necrosis, induced by nitrogen-oxygen stress, and replaces it with
      more mild mechanism of cell death - apoptosis.

PMID- 18071215
TI  - Influence of the new premix with iodine content on the quantitative indices of
      iodine accumulation in egg.
AB  - In order to increase the assortment of food products, enriched with iodine
      natural compound, we decided to study the influence of the new premix with iodine
      content on the quantitative indices of iodine accumulation in eggs. The iodized
      premix was prepared on the spot by A.Kalandarishvili's method. The experiments
      were conducted on 140-250 days old Cross Loman-Classic layer hens. The iodine
      quantitative determination was conducted by the kinetic method. We used the bran
      premix with iodine content, in which optimum concentration of iodine fluctuated
      from 500 up to 1000 mkg, as food additive for the feeding of laying hens taking
      into account the best hematological indices. The correlation between the iodine
      quantity in egg, iodine concentration in premix and the intensity of egg lying
      has been determined.

PMID- 18071217
TI  - [Gastroprotective properties of phytomedicine tiol].
AB  - Phitopreparation tiol is offered (5% fatty solution of Tea Leaf lipid complex) as
      a medicine. To determine gastroprotective effect of tiol generally accepted
      models of acute gastric ulcer were used: bitadion, atopanove and reserprinove
      stomach damages. An experiment was conducted on half-matured white mice weighting
      140-160 g., which fast 24 hours before the experiment (only water was freely
      given to them). Animals were killed by immediate decapitation under light ether
      narcosis. Their stomachs were dissected along greater curvature of stomach and
      number of injuries were counted. The injuries were subdivided into hemorrhage,
      erosion and ulcer. Paul's "ulcer index" was calculated for any kind of damage.
      Each group consisted of 5 mice. Distilled water was used as control and aekol -
      to collate the gastroprotective effect. Results of the experiment showed that
      gastroprotective effect of tiol is greater than that of aekol's.

PMID- 18071216
TI  - [Influence of zafirlucast on the content of leukotrienes, biogenic amines and
      prostaglandins in blood and myocardium in epinephrine-induced heart injury].
AB  - Combination of preventive and repeated (after 12 h) intravenous injection of
      zafirlucast in daily dose of 40 mg/kg to rabbits with epinephrine-induced heart
      injury essentially decreased the content of leukotriene C(4), but did not prevent
      the increase of leukotriene B(4) concentration in the blood, though drcreased its
      content in comparison with the level observed 24 h after epinephrine injection by
      11%. Two injections of zafirlucast had a favorable impact on serotonin content in
      the myocardium (this parameter decreased by 19%), promoted a decrease in
      epinephrine content and normalization of the norepinephrine/epinephrine ratio,
      did not change prostaglandin content and ratio, and slightly diminished histamine
      concentration in the myocardium. The effect of zafirlucast can be explained by a
      reduce of oxidative stress. Zafirlucast decreased blood content of myofibrillar
      fraction of creatine phosphokinase (by 22%). These result suggest that
      zafirlucast can be added to combined therapy of necrotic, stress-induced,
      hypoxic, and ischemic injuries of the myocardium.

PMID- 18071219
TI  - Annual variations of the elemental concentrations of PM10 in ambient air of
      Nagoya City as determined by ICP-AES and ICP-MS.
AB  - PM10 samples were collected at an urban site of Nagoya City during September,
      2003, to August, 2004, and annual variations of the concentrations of the
      elements in PM10 samples were examined by inductively coupled plasma atomic
      emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry
      (ICP-MS). The annual concentration variations of ca. 30 elements in ambient air
      were in the range from sub-ng m(-3) to several microg m(-3). From an evaluation
      by the enrichment factors of the elements, elements such as Al, Ca, Fe, Mg, Ti,
      Mn, Ba, Sr, Ce, La, Nd, Co, Cs, and Pr, in PM10 samples were found to have
      originated mostly from natural sources, while the elements such as S, Zn, Pb, Cu,
      Ni, Sb, Sn, Cd, Bi, W, Tl, and In originated from anthropogenic emission sources.
      Furthermore, in seasonal variations of the elemental concentrations of PM10
      samples in ambient air, the elements originated mostly from natural sources
      provided significantly high concentrations in spring during the "Kosa" period
      (the dust season from March to May). On the other hand, the elements mainly from
      anthropogenic emission sources provided relatively higher concentrations in
      autumn and winter, which may be explained by the fact that the urban atmospheric
      structure is stabilized by the temperature-inversion layer formed over the city
      in those seasons. In addition, all of the elements provided significantly low
      concentrations in the summer, due to the dilution effect of the oceanic winds as
      well as due to the convection of air mass up to the high levels.

PMID- 18071220
TI  - Determination of silicon in high-silicon electrical steel by ICP-AES with on-line
      sample electrolytic dissolution.
AB  - A flow-injection procedure combining electrolytic sample decomposition and
      inductively coupled plasma atomic emission spectrometry (ICP-AES) is proposed in
      order to rapidly determine the content of silicon in high-silicon electrical
      steel. This system is characterized by sample decomposition through electrolysis
      directly coupled to ICP-AES. A steel sample is dissolved by electrolysis using a
      6 mol L(-1) HCl solution as an electrolyte with a flow rate of 5 mL min(-1); the
      electrolyte containing a dissolved sample is subsequently introduced into ICP-AES
      via a nebulizer. The effects of the electrolysis current and the temperature on
      the decomposition of the sample were studied. Samples were electrolyzed under the
      condition of a 1.5 A constant current, at room temperature (25 degrees C) to
      avoid the hydrolysis of silicon to precipitate. Comparing the analytical results
      of steel samples obtained by this analytical system with those obtained by the
      gravimetric method, determined values agreed well quantitatively. The RSD of
      silicon at approximately 3% was 0.3% (n = 6).

PMID- 18071221
TI  - Determination of ulifloxacin by terbium-sensitized fluorescence with second-order
      scattering and its applications.
AB  - This paper reports the determination of ulifloxacin (UFX) by terbium-sensitized
      fluorescence using a second-order scattering method. UFX and Tb(III) ion form a
      fluorescence complex in aqueous solution, and its maximum excitation and emission
      wavelengths are located at 273 and 545 nm, respectively. In optimum conditions,
      the relative intensity at 545 nm has a linear relationship to the concentration
      of UFX in the range of 2.0 x 10(-8) - 1.0 x 10(-5) mol L(-1) and the detection
      limit is 3.9 x 10(-9) mol L(-1). The proposed method was applied to the
      determination of UFX in spiked human serum and urine satisfactorily. The
      luminescence property of UFX is also discussed by comparing with norfloxacin
      (NFLX) and ofloxacin (OFLX).

PMID- 18071222
TI  - Determination of sulpiride in human urine using excitation-emission matrix
      fluorescence coupled with second-order calibration.
AB  - This paper proposes a new and effective approach for the quantitative analysis of
      sulpiride, a significant antipsychotic drug, in human urine samples by the
      incorporation of excitation-emission matrix (EEM) fluorescence and second-order
      calibration methodologies based on the alternating fitting residue (AFR) and self
      weighted alternating trilinear decomposition (SWATLD) algorithms. With the
      application of a second-order advantage, the proposed strategy could be utilized
      for a direct concentration determination of sulpiride with a simple pretreatment
      step, even in the presence of serious natural fluorescent interferences. The
      average recoveries of sulpiride in complex urine samples by using AFR and SWATLD
      with an estimated component number of three were 101.2 +/- 2.1 and 94.4 +/- 0.7%,
      respectively. Moreover, the accuracy of the two algorithms was also evaluated
      through elliptical joint confidence region (EJCR) tests as well as the figures of
      merit, such as sensitivity (SEN), selectivity (SEL) and limit of detection (LOD).
      The experimental results demonstrated that both algorithms, as promising
      quantitative alternatives, have been satisfactorily applied to the determination
      of sulpiride in human urine, but the performance of AFR was slightly better than
      that of SWATLD.

PMID- 18071223
TI  - Flow-injection spectrophotometric determination of novalgin in pharmaceuticals
      using micellar medium.
AB  - A sensitive flow-injection (FI) procedure with spectrophotometric detection in a
      micellar medium is proposed for the determination of novalgin. The method is
      based on the instantaneous formation of a red-orange product (lambda(max) = 510
      nm) after the reaction between novalgin and p-dimethylaminocinnamaldehyde (p-DAC)
      in a dilute acid medium. The sensitivity of this reaction was increased by a
      factor of 5.6 in the presence of sodium dodecyl sulfate (SDS). Experimental
      design methodologies were used to optimize the chemical and FI variables. The
      calibration curve was linear in the range of 1.45 x 10(-6) to 2.90 x 10(-5) mol
      L(-1) with an excellent correlation coefficient (r = 0.9999). The detection limit
      was 1.31 x 10(-7) mol L(-1) (n = 20, RSD = 2.0%). No interferences were observed
      from the common excipients. The results obtained by the proposed method were
      favorably compared with those given by the iodometric reference method at 95%
      confidence level.

PMID- 18071224
TI  - Fast separation and quantification of C60 and C70 fullerenes using thermostated
      micro thin-layer chromatography.
AB  - Thermostated micro planar chromatography was applied for systematic separation
      studies of C60 and C70 fullerenes using n-alkanes as mobile phases on TLC and
      HPTLC plates coated with polyamide, silica gel, aluminum oxide as well as two
      types of octadecylsilica (C18) sorbents. Retention data were collected at
      constant temperature at 20 degrees C (+/-0.05 degrees C) using an unsaturated
      chamber mode with an eluent, such as n-pentane, n-hexane and n-heptane. The
      separation results under both saturated and unsaturated chamber modes for
      selected mobile/stationary phases were also examined, and several parameters,
      including separation factor (alpha) and resolution (R(S)), were compared with
      data obtained with high-performance liquid chromatography conditions.
      Interestingly, C60/C70 fullerenes separation performed on HPTLC plates with a
      developing distance of 45 mm was better for those observed on a 25 cm length
      analytical HPLC column under similar conditions to that on carbon coverage of the
      stationary phase, n-hexane as the mobile phase and separation temperature (R(S) =
      1.84 and 1.68 for HPTLC, and HPLC, respectively). Moreover the advantage of the
      planar chromatographic separation of fullerenes studied is a short elution time
      of less than 6 min. Furthermore, the reported separation protocol shows a
      capability for the evaluation of fullerenes quantity in commercial samples.

PMID- 18071225
TI  - Analysis of the temperature and pressure dependence of the 129Xe NMR chemical
      shift and signal intensity for the derivation of basic parameters of adsorption
      as applied to zeolite ZSM-5.
AB  - Temperature and pressure dependences of the 129Xe NMR chemical shift and the
      signal intensity have been investigated using ZSM-5 as an adsorbent under routine
      conditions without using any high-pressure or especially high-temperature
      facilities. The use of a rigorously shielded system and a calibration sample for
      the signal intensity was found to be valuable to obtain reliable data about the
      chemical shift and the signal intensity. The 129Xe NMR data obtained between 0.05
      and 1.5 atm and from 24 to 80 degrees C were analyzed based on the Dubinin
      Radushkevich equation as well as the Langmuir type equation. In both analyses,
      chemical shift data succeeded only partially in providing the profile of
      adsorption, such as energetic aspects, surface area, saturated amount of Xe
      adsorption and specific parameters of 129Xe chemical shift. It was shown that the
      reliable total analysis was achieved when the chemical shift data were used
      together with the intensity data. Such an analysis of the chemical shift data,
      aided by the intensity data, will be useful in performing nano-material analysis
      on 129Xe NMR without invoking the traditional methodology of gravimetric or
      volumetric adsorption experiments.

PMID- 18071226
TI  - Separation and preconcentration of gallium(III), indium(III), and thallium(III)
      using new hydrazone-modified resin.
AB  - Ga(III), In(III) and Tl(III) ions in the presence of different sulfate salts have
      been successfully separated using 1-(3,4-dihydroxybenzaldehyde)-2
      acetylpyridiniumchloride hydrazone (DAPCH) loaded on Duolite C20 in batch and
      column modes. The obtained modified resin as well as the metal complexes was
      characterized by elemental analysis and infrared spectra. The extraction
      isotherms were determined at different pH values. Ga(III) and In(III) are sorbed
      from aqueous solution at pH 2.5 - 3.0 while Tl(III) is sorbed at 2.0. The
      stripping of the adsorbed ions can be carried out using different concentrations
      of HCl as eluent. The saturation sorption capacities of Ga(III), In(III) and
      Tl(III) were 0.82, 0.96 and 0.44 mmol g(-1), where the preconcentration factors
      are 150, 150 and 100, respectively. The metal(III):Duolite C20-DAPCH ratio was
      1:2 for Tl(III) and 1:1 for In(III) and Ga(III). The loaded resin can be
      regenerated for at least 50 cycles. The utility of the modified resin was tested
      in aqueous samples and the results show an RSD value of < 5% reflecting their
      accuracy and reproducibility.

PMID- 18071227
TI  - Separation and simultaneous determination of uric acid and ascorbic acid on a
      dynamically modified poly(dimethylsiloxane) microchip.
AB  - Poly(dimethylsiloxane) microfluidic channels alternately modified by
      poly(diallyldimethylammonium chloride) and poly(sodium 4-styrenesulfonate) were
      successfully used to separate uric acid and ascorbic acid. Results show that uric
      acid and ascorbic acid can be well separated and detected simultaneously in
      modified microchips coupled with in-channel electrochemical detection. Under the
      optimal conditions, the linear ranges of uric acid and ascorbic acid were both
      from 25 to 600 microM, with the correlation coefficients of 0.997 and 0.996,
      respectively. The detection limits were 8 microM for uric acid and 5 microM for
      ascorbic acid. Factors influencing separation and detection, including buffer
      solution, detection potential and separation voltage, were investigated and
      optimized. In addition, the dependences of the current response on sensitivity
      and reproducibility were studied, and the stability of the device was also
      evaluated in detail. This method was successfully used to determine uric acid and
      ascorbic acid in human urine.

PMID- 18071228
TI  - Ferrocenylnaphthalene diimide-based electrochemical ribonuclease assay.
AB  - Messenger RNA (mRNA) poly(A)+RNA (from mouse kidney) was immobilized on a N
      hydroxysuccinimide(NHS)-activated carboxylic acid modified electrode prepared by
      the treatment of a gold electrode with 3,3'-dithiodipropionic acid, followed by
      NHS and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). An electrochemical
      measurement using this mRNA electrode was carried out in an electrolyte
      containing ferrocenylnaphthalene diimide (1), and showed an electrochemical
      signal based on 1 concentrated on immobilized mRNA. After treating this electrode
      with water containing varied amounts of ribonuclease A (RNase A), the current
      peak based on 1 decreased with increasing in the amount of RNase A with a linear
      correlation in the range of 0.2-10 pg of RNase A.

PMID- 18071229
TI  - Electrochemical determination of nitrite using a gold nanoparticles-modified
      glassy carbon electrode prepared by the seed-mediated growth technique.
AB  - Seed-mediated growth of gold nanoparticles on glassy carbon (GC) surfaces was
      developed. The field emission scanning electron microscopy (FE-SEM) and
      electrochemical characterization confirmed the effective attachment of gold
      nanoparticles on GC surface with such a wet-chemical method. The as-prepared gold
      nanoparticles attached glassy carbon electrode (Au/GCE) presented excellent
      catalytic ability toward the oxidation of nitrite. Compared with bare GCE and
      planar gold electrode, the Au/GCE obviously decreased the overpotential of
      nitrite oxidation and improved the peak current. The catalytic current was found
      to be linearly proportional to the nitrite concentration in the range of 1 x 10(
      5) - 5 x 10(-3) M, with a detection limit of 2.4 x 10(-6) M. The Au/GCE was
      successfully applied to the electrochemical determination of nitrite in a real
      wastewater sample, showing excellent stability and anti-interference ability.

PMID- 18071230
TI  - Extraction behavior and separation of lanthanides with a diglycol amic acid
      derivative and a nitrogen-donor ligand.
AB  - The extraction and separation of lanthanides have been investigated using CHON
      type extractants, which are composed of only C, H, O, and N atoms. N,N
      Dioctyldiglycol amic acid (DODGAA) showed high extraction and separation
      performances for heavier lanthanides compared with typical CHON-type extractants.
      On the other hand, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN)
      provided an unprecedentedly high selectivity for lighter lanthanides.
      Furthermore, it was found that the combination of DODGAA and TPEN under suitable
      conditions enabled the mutual separation of light, middle, and heavy lanthanides.

PMID- 18071232
TI  - Determination of tin by resin-suspension electrothermal atomic absorption
      spectrometry after enrichment as the complex with ammonium
      pyrrolidinedithiocarbamate.
AB  - A resin-phase extraction method has been optimized for the trace determination of
      tin(II) by ETAAS. Tin(II) was extracted on a finely divided anion exchange resin
      as the complex with ammonium pyrrolidinedithiocarbamate (APDC). The resin was
      collected on a membrane filter and then dispersed in 1.00 ml of 1 mol l(-1)
      nitric acid containing 100 microg of Pd(II) and 60 microg of Ni(II). The
      resulting resin suspension was subjected to GFAAS. The proposed method was
      applied to the determination of tin(II) in hydrochloric acid.

PMID- 18071231
TI  - Adsorption behavior of cationic and anionic species on chitosan resins possessing
      amino acid moieties.
AB  - Chitosan resins modified with amino acids, such as glycine, valine, leucine, and
      serine, were synthesized for investigating the adsorption behavior of cationic
      and anionic species, and showed good abilities for the adsorption of trace
      elements in aquatic media as follows: glycine for lanthanoids at pH 7, leucine
      for molybdenum at pH 1-5, serine for uranium at pH 2-7, and amino acids for
      bismuth at pH 1-7. Cationic and anionic species could be adsorbed by a chelating
      mechanism and an anion-exchange mechanism.

PMID- 18071233
TI  - Analysis of a quasi-elastic laser scattering spectrum using the maximum entropy
      method.
AB  - We have applied the maximum entropy method (MEM) to the analysis of quasi-elastic
      laser scattering (QELS) spectra and have established a technique for determining
      capillary wave frequencies with a higher time resolution than that of the
      conventional procedure. Although the QELS method has an advantage in time
      resolution over mechanical methods, it requires the averaging of at least 20-100
      power spectra for determining capillary wave frequencies. We find that the MEM
      analysis markedly improves the S/N ratio of the power spectra, and that averaging
      the spectra is not necessary for determining the capillary wave frequency, i.e.,
      it can be estimated from one power spectrum. The time resolution of the QELS
      attains the theoretical limit by using MEM analysis.

PMID- 18071234
TI  - A rapid sample pretreatment protocol: improved sensitivity in the detection of a
      low-abundant serum biomarker for prostate cancer.
AB  - We have developed a rapid immunoglobulin G (IgG) and a human serum albumin (HSA)
      depletion protocol. We depleted both HSA and IgG (> 97%) separately, and in a
      single procedure. The method is specific and reproducible (RSD < 1.0%), and
      substantially lowered the detection limit of prostate-specific antigen, a
      prostate cancer biomarker. The method can be applied to other biomarkers and
      proteomic studies. Interestingly, the depletion of HSA might not be blankly as
      beneficial as widely portrayed. Our study suggests the depletion of IgG to be
      more beneficial than albumin depletion.

PMID- 18071235
TI  - A fast, simple calibration method for organic carbon isotope analysis using
      continuous-flow elemental analyzer interfaced with an isotope ratio mass
      spectrometer.
AB  - Continuous flow analysis using an elemental analyzer interfaced with an isotope
      ratio mass spectrometer (EA-IRMS) is faster and requires much less material than
      conventional analytical methods. Although using an EA-IRMS is simple and fast,
      accurate calibration strongly depends on matching sample and reference peak
      heights by adjusting the sample weight. This paper describes a new modification
      for calibration using only the major ion beam intensity (nA) without weighing
      each sample or increasing the number of reference materials.

PMID- 18071237
TI  - A real-time quantitative PCR detection method for pork, chicken, beef, mutton,
      and horseflesh in foods.
AB  - A rapid real-time quantitative PCR method to detect trace amounts of pork,
      chicken, beef, mutton, and horseflesh in foods was developed. The primers and
      TaqMan MGB (minor groove binder) probes were designed on the gene encoding
      cytochrome b for the specific detection of each species. The limit of
      quantification of this method was found to be 100 fg/microl of each mitochondrial
      DNA in 10 ng/microl of the wheat mitochondrial DNA matrix. The calculated R(2)
      values of the standard curves for the five species ranged between 0.994 and
      0.999. This method would be particularly useful in the detection of hidden meat
      mince in processed foods, which would verify food labeling and gain consumers'
      trust.

PMID- 18071238
TI  - Impaired thermoregulatory ability of oxytocin-deficient mice during cold
      exposure.
AB  - We analyzed temperature homeostasis in oxytocin-deficient (Oxt(-/-)) mice and
      found that Oxt(-/-) mice exhibited lower body temperatures than wild-type animals
      when they were exposed to cold. Oxt(-/-) mice also showed slightly more weight
      gain, but there were no obvious differences in the morphology of white and brown
      adipose tissues as between wild-type and Oxt(-/-) mice. In cold-exposed
      conditions, oxytocin neurons containing c-Fos immunoreactivity existed in the
      paraventricular nucleus of the hypothalamus. These results suggest that the
      central oxytocin neurons constitute part of the thermoregulatory system involved
      in maintaining body temperature in cold environments.

PMID- 18071239
TI  - Momilactone A and B as allelochemicals from moss Hypnum plumaeforme: first
      occurrence in bryophytes.
AB  - Momilactones A (1) and B (2), which have been identified as phytoalexins in rice,
      were isolated from extracts of the moss Hypnum plumaeforme. This is the first
      isolation and identification of momilactones as allelochemicals from a bryophyte.
      H. plumaeforme produces considerable amounts of momilactones (isolated yield: 8.4
      mg/Kg plant for 1; 4.2 mg/Kg for 2). EtOAc extracts from H. plumaeforme and 2
      showed growth inhibitory activity against angiosperms, moss, and liverwort
      plants. On the other hand, the growth of H. plumaeforme was insensitive to its
      extract and 2. Our finding suggests that momilactones play an important role as
      allelochemicals in this moss.

PMID- 18071240
TI  - Annexin A3-expressing cellular phenotypes emerge from necrotic lesion in the
      pericentral area in 2-acetylaminofluoren/carbon tetrachloride-treated rat livers.
AB  - Recently we found a small hepatocyte-specific protein, annexin A3 (AnxA3), in
      fractionated adult rat hepatocytes. Here we describe the results of an in vivo
      demonstration of AnxA3-expressing cellular phenotypes in the liver with 2
      acetylaminofluoren (2-AAF)/carbon tetrachloride (CCl(4))-injury. In association
      with an elevation of alanine amino transferase (ALT) and aspartic acid amino
      transferase (AST) activities, hepatic AnxA3 mRNA increased markedly. AnxA3
      positive cells were detected in clustered cells present in or emerging from the
      pericentral region. These albumin-expressed cells were histologically similar to
      cells expressing CD34, a hematopoietic cell marker protein. The number of
      clusters decreased in the days following CCl(4) treatment, and annexin-negative,
      but albumin-positive, oval cells appeared. We concluded that the agent-induced
      liver defect initially recruits bone marrow-derived cells, and that it promotes
      differentiation of these cells into AnxA3-positive cells, followed by emergence
      of the oval cells, which might have a role in the restitution of the damaged
      liver.

PMID- 18071241
TI  - Texture of cooked rice prepared from aged rice and its improvement by reducing
      agents.
AB  - The textures of cooked rice prepared from aged rice grains and their improvement
      by reducing agents were investigated. For aged rice that was stored for 5 months
      without air by the operation of a vacuum packing machine, the stickiness/hardness
      ratio of cooked rice was as low as that of aged rice stored in air. The results
      of electrophoresis showed that oxidation of proteins in the former was advanced
      to the same degree as in the latter. The stickiness/hardness ratios of the aged
      rice were increased by the addition of sodium sulfite, cysteine, and
      dithiothreitol to the cooking water. Sodium sulfite, cysteine, and dithiothreitol
      cleave disulfide bonds to sulfhydryl groups. Therefore, cleaving disulfide bonds
      to sulfhydryl groups improved the texture. The addition of them to the cooking
      water also increased the extractable solids at the time of heating. Hence
      cleaving disulfide bonds to sulfhydryl groups must increase extractable solids.
      Consequently, the gelatinized paste layer thickened and the thick paste layer
      softened the cooked rice.

PMID- 18071242
TI  - Anti-peptide antibody production elicited by in vitro immunization of human
      peripheral blood mononuclear cells.
AB  - Human monoclonal antibodies have great potential for use in the treatment of
      various diseases. We have established an in vitro immunization protocol for
      inducing antigen-specific antibody production from human peripheral blood
      mononuclear cells (PBMCs). In the in vitro immunization protocol, PBMCs are
      pretreated with L-leucyl-L-leucine methyl ester (LLME) to remove suppressive
      cells, and are sensitized and cultured with a soluble antigen in the presence of
      IL-2, IL-4 and muramyl dipeptide for 8 d, and then an antigen-specific antibody
      is produced. In this study, we examined the novel possibility of an in vitro
      immunization protocol, specifically, whether LLME-treated PBMCs can be sensitized
      with a peptide antigen to produce an anti-peptide antibody. The results indicate
      that antigen-specific immune responses were elicited by a peptide antigen derived
      from rice allergen, a cholera toxin B subunit, and TNF-alpha as a sensitizing
      antigen in in vitro immunization. These results suggest that the in vitro
      immunization protocol is applicable in the generation of an anti-peptide antibody
      against various antigens, including food allergens, foreign antigens, and self
      antigens.

PMID- 18071243
TI  - Plant-type N-glycans containing fucose and xylose in Bryophyta (mosses) and
      Tracheophyta (ferns).
AB  - The presence of typical plant-type N-glycans (eg, M3FX, Gn2M3FX, and Le(a)2M3FX)
      in mosses, ferns, and other organisms was examined to determine which plant
      initially acquired glycosyltransferases to produce plant-type N-glycans during
      organic evolution. No M3FX-type N-glycan was detected in lichens (Cladonia
      humilis) or in any one of the three preland plants Enteromorpha prolifera, Ulva
      pertusa Kjellman, and Chara braunii Gmelin. In Bryophyta, M3FX-type N-glycan was
      detected at trace amounts in Anthocerotopsida (hornworts) and at certain amounts
      in Bryopsida (mosses), but not in Hepaticopsida (liverworts). Le(a)2M3FX was
      detected in some Bryopsida of relatively high M3FX content. Most Tracheophyta
      (ferns and higher plants) contained the three typical M3FX-type glycans as the
      main N-glycans in different ratios. These results suggest that organisms acquired
      xylosyltransferase and fucosyltransferase during the development of mosses from
      liverworts, and that later all plants retained both enzymes. Bryopsida have also
      obtained galactosyltransferase and fucosyltransferase to synthesize the Le(a)
      antigen.

PMID- 18071244
TI  - Cloning, expression, and transcription analysis of L-arabinose isomerase gene
      from Mycobacterium smegmatis SMDU.
AB  - The L-arabinose metabolic gene cluster, araA, araB, araD, araG, araH and araR,
      encoding L-arabinose isomerase (L-AI) and its accessory proteins was cloned from
      Mycobacterium smegmatis SMDU and sequenced. The deduced amino acid sequence of
      araA displayed highest identity with that of Bacillus subtilis (52%). These six
      genes comprised the L-arabinose operon, and its genetic arrangement was similar
      to that of B. subtilis. The L-AI gene (araA), encoding a 501 amino acid protein
      with a calculated molecular mass of 54,888 Da, was expressed in Escherichia coli.
      The productivity and overall enzymatic properties of the recombinant L-AI were
      almost same as the authentic L-AI from M. smegmatis. Although the recombinant L
      AI showed high substrate specificity, as did L-AI from other organisms, this
      enzyme catalyzed not only isomerization of L-arabinose-L-ribulose and D-galactose
      D-tagatose but also isomerization of L-altrose-L-psicose and L-erythrulose-L
      threose. In combination with L-AI from M. smegmatis, L-threose and L-altrose can
      be produced from cheap and abundant erythritol and D-fructose respectively,
      indicating that this enzyme has great potential for biological application in
      rare sugar production. Transcription analysis using various sugars revealed that
      this enzyme was significantly induced not only by L-arabinose and D-galactose but
      also by L-ribose, galactitol, L-ribulose, and L-talitol. This different result of
      transcription mediated by sugars from that of E. coli suggests that the
      transcriptional regulation of araA from M. smegmatis against sugar is loose
      compared with that from E. coli, and that it depends on the hydroxyl
      configuration at C2, C3 and C4 positions of sugars.

PMID- 18071245
TI  - Immunoassay using microfluid filters constructed by deep X-ray lithography.
AB  - Microfluid filters were fabricated, which possessed 2,100 cylindrical through
      bores (psi 40 microm) in 200 microm-thickness polymethylmethacrylate (PMMA)
      sheets (psi 3 mm), by deep X-ray lithography using synchrotron radiation. To
      evaluate the microfluid filters as a device for an immunoassay, we bound the goat
      anti-mouse immunoglobulin G (IgG) antibody to the surface of the filters, and set
      the filters between reaction vessels stacked vertically in a microreactor. An
      enzyme-linked immunosorbent assay (ELISA) of mouse IgG using the goat anti-mouse
      IgG/horseradish-peroxidase (HRP) conjugate indicated that mouse IgG could be
      quantitatively detected in the range of 0-100 ng/ml, demonstrating the
      applicability of vertical microfluidic operation to the immunoassay.

PMID- 18071246
TI  - Studies on the later stage of the biosynthesis of pleuromutilin.
AB  - Mutilin (4) and deoxy analogues 2 and 3 are biosynthetic precursors of
      pleuromutilin (1) in the later stage of biosynthesis. Precursors 2 and 3 are
      required for studies on the oxygenation steps in biosynthesis, and were
      synthesized from readily available 1 via 4 by deoxygenation of the hydroxy
      groups. Feeding experiments with the (2)H-labeled precursors confirmed their
      microbial conversion into 1.

PMID- 18071247
TI  - Bioproduction of D-psicose from allitol with Enterobacter aerogenes IK7: a new
      frontier in rare ketose production.
AB  - D-psicose, a new alternative sweetener, was produced from allitol by microbial
      oxidation of the newly isolated strain Enterobacter aerogenes IK7. Cells grown in
      tryptic soy broth medium (TSB) supplemented with D-mannitol at 37 degrees C were
      found to have the best oxidation potential. The cells, owing to broad substrate
      specificity, oxidized various polyols (tetritol, pentitol, and hexitol) to
      corresponding rare ketoses. By a resting cell reaction, 10% of allitol was
      completely transformed to the product D-psicose, which thus becomes economically
      feasible for the mass production of D-psicose. Finally, the product was
      crystallized and confirmed to be D-psicose by analytical methods.

PMID- 18071248
TI  - Comparative analyses of viable bacterial counts in foods and seawater under
      microplate based liquid- and conventional agar plate cultivation: increased
      culturability of marine bacteria under liquid cultivation.
AB  - Bacterial counts under liquid cultivation using 96-well microplates were
      performed. The counts under liquid and under solid cultivation were equivalent in
      foods, although the counts under liquid cultivation exceeded those under solid
      cultivation in seawater, suggesting that some bacteria in seawater were viable
      but did not form detectable colonies. Phylogenetic analysis of bacteria obtained
      under liquid cultivation was also performed.

PMID- 18071249
TI  - Identification of a fatty acyl-CoA synthetase gene, lcf2+, which affects
      viability after entry into the stationary phase in Schizosaccharomyces pombe.
AB  - The lcf1(+) gene, which encodes a long chain fatty acyl-CoA synthetase, is
      necessary for the maintenance of viability after entry into the stationary phase
      in Schizosaccharomyces pombe. In this study, we analyzed a paralogous gene,
      SPBP4H10.11c (named lcf2(+)), and we present evidence that the gene encodes a new
      fatty acyl-CoA synthetase. The enzyme preferentially recognized myristic acid as
      a substrate. A Deltalcf2 mutant showed increased viability after entry into the
      stationary phase in SD medium. A Deltalcf1Deltalcf2 double mutant showed a severe
      decrease in long-chain fatty acyl-CoA synthetase activity and a rapid loss of
      viability after entry into the stationary phase. These results suggest that fatty
      acid utilization and/or metabolism is important to determine viability in the
      stationary phase.

PMID- 18071250
TI  - Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam
      (Dioscorea spp.), on high-cholesterol fed rats.
AB  - Diosgenin (a steroidal saponin of yam) has long been used as a raw material for
      the industrial production of steroid drugs, and reported to have a
      hypocholesterolemic effect by suppressing cholesterol absorption and increasing
      cholesterol secretion. Oxidative stress has been suggested as a main risk factor
      in the development of atherosclerosis. The aim of this study is to investigate
      the possible hypolipidemic and antioxidative effect of diosgenin on rats fed with
      a high-cholesterol diet supplemented with either 0.1% or 0.5% diosgenin for 6
      weeks. We measured the lipid profile in the plasma and liver, lipid peroxidation
      and antioxidative enzyme activities in the plasma, erythrocyte and gene
      expression of antioxidative enzymes in the liver, and the oxidative DNA damage in
      lymphocytes. Diosgenin showed a decrease in the plasma and hepatic total
      cholesterol levels, but increased the plasma high-density lipoprotein (HDL)
      cholesterol level. Erythrocyte TBARS and lymphocyte DNA damage measured by the
      comet assay were decreased in the diosgenin supplemented group. Furthermore,
      diosgenin feeding enhanced the resistance to lymphocyte DNA damage caused by an
      oxidant challenge with H(2)O(2). The antioxidative enzyme activities were also
      affected by diosgenin supplementation. Total superoxide dismutase (SOD) in the
      plasma and liver, glutathione peroxidase (GSH-Px) in erythrocytes, and catalase
      (CAT) in erythrocytes and liver were significantly increased in the 0.5%
      diosgenin group. The expression of antioxidative enzymes was up-regulated by
      diosgenin, the expression of GSH-Px being the highest in the 0.5% diosgenin
      group. These results suggest that diosgenin could be a very useful compound to
      control hypercholesterolemia by both improving the lipid profile and modulating
      oxidative stress.

PMID- 18071251
TI  - New polar constituents of the pupae of the silkworm Bombyx mori L. I. Isolation
      and identification of methionine sulfoxide, methionine sulfone, and gamma-cyclic
      di-L-glutamate.
AB  - In addition to serine (L:D = 68:32), methionine sulfoxide (MSO), L-methionine
      sulfone (L-MSO(2)), and disodium gamma-cyclic di-L-glutamate were identified in a
      methanol extract of Bombyx mori L. pupae. MSO was isolated in a diastereomeric
      mixture of L(+)- and D(+)-MSO in a ratio of 99:1. The presence of these compounds
      in other developmental stages, including eggs, larvae (1st, 4th, 5th, and mature
      5th instar), adults, and excrement (feces and urine) was investigated. The L(+)
      isomer of MSO was present in extracts of the 1st and 5th instar larvae, adults,
      and eggs, but was not detected in feces or urine. The D(+)-isomer was found only
      in pupal stage extracts, and was excreted into the meconium with L(+)-isomer. L
      MSO(2) and gamma-cyclic di-L-glutamate were not detected at other insect life
      stages or in the insect excrement. gamma-Cyclic di-L-glutamate is thought be
      produced due to blockage of the glutamate synthetic pathway (glutamine
      synthetase) by L-MSO(2) and Mg(2+). The biochemical role of L-MSO(2) during the
      pupal life stage remains unknown, but importantly, the stage-specific expression
      suggests that it is a candidate molecule for the induction of diapause.

PMID- 18071252
TI  - Effects of polysaccharide derived from black currant on relieving clinical
      symptoms of Japanese cedar pollinosis: a randomized double-blind, placebo
      controlled trial.
AB  - We investigated the efficacy of the polysaccharide derived from black currant,
      named cassis polysaccharide (CAPS), for inhibiting Japanese cedar pollinosis
      symptoms and improving quality of life by a randomized double-blind, placebo
      controlled trial in 2006. A total of 28 subjects were enrolled in the study, and
      10 subjects in each group completed the trial. Although there was no significant
      difference between the CAPS and placebo group in the weekly mean value of any
      symptom in the daily symptom diary at any time, a smaller degree of final symptom
      aggravation was found in the CAPS group. Significant aggravation of the score was
      finally observed in the placebo group with inferior conch swelling and with
      sneezing, itchy nose, itchy eye and watery eye in the Japan rhino-conjunctivitis
      quality of life questionnaire assessment, while the changes observed in the CAPS
      group were not significant. In conclusion, our findings clearly indicate that
      CAPS would be useful as a food supplement in assisting the treatment of Japanese
      cedar pollinosis.

PMID- 18071253
TI  - Relationship between the stability of hen egg-white lysozymes mutated at sites
      designed to interact with alpha-helix dipoles and their secretion amounts in
      yeast.
AB  - The positively charged lysine at the C-terminals of three long alpha-helices (5
      15, 25-35, and 88-99) was replaced with alanine (K13A, K33A, K97A) or aspartic
      acid (K13D, K33D, K97D) in hen lysozyme by genetic engineering. The denaturation
      transition point (Tm) and Gibbs energy change Delta G of the mutant lysozymes
      decreased remarkably, suggesting that the positive charge at the C-terminals of
      helices is involved in the stabilization of the helix dipole. On the other hand,
      the non-charged asparagine at the N-terminal of the long alpha-helices (25-35 and
      88-99) was replaced with negatively charged aspartic acid (N27D and N93D). The Tm
      and Delta G of N27D increased, suggesting that the dipole moment of the N
      terminal of the helices is diminished by replacement with negatively charged
      amino acid strengthening the stability of the helices. The stabilities of those
      hen egg white lysozymes mutated at the N- or C-terminal sites of the three long
      alpha-helices were related with their secretion amounts in yeast (Pichia
      pastoris). The secretion amounts of these mutant lysozymes in yeast were closely
      correlated with their stability.

PMID- 18071255
TI  - Ethyl esterification of long-chain unsaturated fatty acids derived from grape
      must by yeast during alcoholic fermentation.
AB  - The composition of total fatty acid ethyl ester (FAEE) in yeast cells and the
      liquid phase separated from grape must during alcoholic fermentation at different
      temperatures was investigated by using the solid-phase extraction method.
      Thirteen FAEE from butyric to linolenic acids were detected during fermentation.
      Significant amounts of long-chain unsaturated FAEE, including linoleic and
      linolenic acids derived from grape material, had already accumulated in the yeast
      cells by day 3 during fermentation.

PMID- 18071254
TI  - Structural analysis of the fundamental polymer of the sheath constructed by
      Sphaerotilus natans.
AB  - The sheath of Sphaerotilus natans is composed of cysteine-rich peptide and
      polysaccharide moieties. The polysaccharide was prepared by treating the sheath
      with hydrazine, and was determined to be a mucopolysaccharide containing beta-D
      GlcA, beta-D-Glc, alpha-D-GalN, and beta-D-GalN. To elucidate the structure of
      the peptide, the sheath was labeled with a thiol-selective fluorogenic reagent, 4
      (aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole. Enantiomeric determination of the
      S-derivatized Cys in the fluorescent sheath suggested that it contained L-Cys
      mainly. Fluorescent cysteinylglycine was detected in the partial acid hydrolysate
      of the fluorescent sheath. The sheath-degrading enzyme secreted by Paenibacillus
      koleovorans produced a fluorescent disaccharide-dipeptide composed of GalN, Gly,
      and N-acetylated Cys from the fluorescent sheath. The disaccharide and dipeptide
      moieties were found to be connected by an amide bond. Based on these results, the
      sheath was deduced to be formed by association of a mucopolysaccharide modified
      with N-acetyl-L-cysteinylglycine.

PMID- 18071256
TI  - Identification of a jasmonic acid-responsive region in the promoter of the rice
      12-oxophytodienoic acid reductase 1 gene OsOPR1.
AB  - The rice 12-oxophytodienoic acid reductase 1 gene (OsOPR1), isolated as a
      jasmonic acid (JA)-responsive gene, has been suggested to be involved in defense
      responses in rice. We identified a 19-base pair region that is essential to the
      JA-responsiveness of OsOPR1 by deletion and mutation analysis of the promoter by
      dual luciferase assay. This region contains possible recognition sites for basic
      leucine zipper transcription factors.

PMID- 18071257
TI  - A new method for the modification of fibroin heavy chain protein in the
      transgenic silkworm.
AB  - We constructed a new plasmid vector for the production of a modified silk fibroin
      heavy chain protein (H-chain) in the transgenic silkworm. The plasmid (pHC-null)
      contained the promoter and the 3' region of a gene encoding the H-chain and the
      coding regions for the N-terminal domain and the C-terminal domain of the H
      chain. For the model protein, we cloned a foreign gene that encoded EGFP between
      the N-terminal domain and the C-terminal domain in pHC-null and generated
      transgenic silkworms that produced a modified H-chain, HC-EGFP. Transgenic
      silkworms produced HC-EGFP in the posterior part of silk gland cells, secreted it
      into the lumen of the gland, and produced a cocoon with HC-EGFP as part of the
      fibroin proteins. N-terminal sequencing of HC-EGFP localized the signal sequence
      cleavage site to between positions A((21)) and N((22)). These results indicate
      that our new plasmid successfully produced the modified H-chain in a transgenic
      silkworm.

PMID- 18071258
TI  - Multi-well chip for forming a uniform embryoid body in a tiny droplet with mouse
      embryonic stem cells.
AB  - A multi-well chip (MWC) is described by which mouse embryonic carcinoma (EC) stem
      cells form a comparatively more rapid and uniform embryoid body (EB) over the
      conventional hanging drop (HD) method. The newly developed MWC consists of an
      array of extruded through-holes, each of which holds a droplet of the cell
      suspension. The study found that the small curvature radius of the droplet in the
      MWC improved the EB formation rate of a hanging drop from 70% to 98%.
      Furthermore, the EBs formed by the MWC were uniformly round in shape regardless
      of the number of suspended cells ranging from 0.5 x 10(3) to 20 x 10(3). The
      ratio of beating colonies from the MWC was over 2-fold larger than that from HD.
      The experiments demonstrate that the MWC will be a valuable experimental tool for
      robust and reproducible EB-based differentiation of a defined number of ES cells.

PMID- 18071259
TI  - A simple method for multiple modification of the Escherichia coli K-12
      chromosome.
AB  - We developed a simple method of generating markerless deletions in the
      Escherichia coli chromosome. The method consists of two recombination events
      stimulated by lambda Red recombinase. The first recombination replaced a target
      region with a marker cassette and the second then eliminated the marker cassette.
      The marker cassette included an antibiotic resistant gene and a negative
      selection marker (Bacillus subtilis sacB). Since sacB makes E. coli sensitive to
      sucrose, a markerless deletion strain was successfully selected using its sucrose
      resistant phenotype. To stimulate these recombination events, 1-kbp homologous
      sequences adjacent to the target region were connected to both ends of the marker
      cassette or connected to each other by PCR. The average efficiency of the
      recombinations was 24% and 93% respectively. Eliminating the marker cassette with
      a fragment including an additional sequence, insertion was also possible. This
      markerless deletion method should be useful in creating a highly modified E. coli
      chromosome.

PMID- 18071260
TI  - The first thermophilic alpha-oxoamine synthase family enzyme that has activities
      of 2-amino-3-ketobutyrate CoA ligase and 7-keto-8-aminopelargonic acid synthase:
      cloning and overexpression of the gene from an extreme thermophile, Thermus
      thermophilus, and characterization of its gene product.
AB  - The first thermophilic alpha-oxoamine synthase family enzyme was identified. The
      gene (ORF TTHA1582), which is annotated to code putative alpha-oxoamine synthase
      family enzymes, 7-keto-8-aminopelargonic acid (KAPA) synthase (BioF, 8-amino-7
      oxononanoate synthase, EC 2.3.1.47) and 2-amino-3-ketobutyrate CoA ligase (KBL,
      EC 2.3.1.29), in a genomic database, was cloned from an extreme thermophile,
      Thermus thermophilus, and overexpressed in Escherichia coli. The recombinant
      TTHA1582 protein was purified and characterized. It exhibited activity of BioF,
      which catalyzes the condensation of pimeloyl-CoA and L-alanine to produce a
      biotin intermediate KAPA, CoASH, and CO(2) with pyridoxal 5'-phosphate as a
      cofactor. The protein is a dimer with a subunit of 43 kDa that shows an amino
      acid sequence identity of 35% with E. coli BioF. The optimum temperature and pH
      were about 70 degrees C and about 6.0. The enzyme showed high thermostability at
      temperatures of up to 70 degrees C for 1 h, and a half-life of 1 h at 80 degrees
      C. Thus the TTHA1582 protein was found to have the highest optimum temperature
      and thermostablility of the alpha-oxoamine synthase family enzymes so far
      reported. Substrate specificity experiments revealed that it was also able to
      catalyze the KBL reaction, which used acetyl-CoA and glycine as substrates, and
      that enzyme activity was seen with the following combinations of substrates:
      acetyl-CoA and glycine, L-alanine, or L-serine; pimeloyl-CoA and L-alanine,
      glycine, or L-serine; palmitoyl-CoA and L-alanine. This suggests that the
      recombinant TTHA1582 protein has broad substrate specificity, unlike the reported
      mesophilic enzymes of the alpha-oxoamine synthase family.

PMID- 18071261
TI  - MyD88 but not TLR2, 4 or 9 is essential for IL-12 induction by lactic acid
      bacteria.
AB  - Although lactic acid bacteria (LAB) affect the immune system, for example, having
      an anti-allergic effect, little is known about the actual mechanisms of immune
      modulation. Toll-like receptors (TLRs) recognize conserved microbial molecular
      patterns, and are presumed to be involved in the recognition of LAB. However,
      there are few detailed reports examining the relationships between TLR and LAB.
      We measured here production of IL-12, a cytokine considered to play an important
      role in anti-allergic effects, induced by Lactobacillus paracasei strain KW3110
      and other typical LAB by cells from TLR2-, TLR4-, TLR9- and myeloid
      differentiation factor 88 (MyD88)-deficient mice. Unexpectedly, similar cytokine
      production from wild-type and TLR2-, 4- and 9-deficient mice was observed. In
      contrast, cells from MyD88-deficient mice failed to respond to stimulation with
      LAB. It is therefore concluded that although LAB, including strain KW3110, are
      not likely to be recognized by TLR2, 4 or 9, MyD88 is essential for the response
      to these bacteria.

PMID- 18071262
TI  - Molecular cloning and characterization of an alpha-amylase from Pichia burtonii
      15-1.
AB  - An alpha-amylase secreted by Pichia burtonii 15-1 isolated from a traditional
      starter murcha of Nepal, named Pichia burtonii alpha-amylase (PBA), was studied.
      The gene was cloned and its nucleotide sequence was determined. PBA was deduced
      to consist of 494 amino acid residues. It shared certain degrees of amino acid
      sequence identity with other homologous proteins: 60% with Schwanniomyces
      occidentalis alpha-amylase, 58% with Saccharomycopsis sp. alpha-amylase, and 47%
      with Taka-amylase A from Aspergillus oryzae. A three-dimensional structural model
      of PBA generated using the known three-dimensional structure of Taka-amylase A as
      a template suggested high structural similarity between them. Kinetic analysis
      revealed that the K(m) values of PBA were lower than those of Taka-amylase A for
      the oligosaccharides. Although the k(cat) values of PBA were lower than those of
      Taka-amylase A for the oligosaccharide substrates, the k(cat)/K(m) values of PBA
      were higher.

PMID- 18071263
TI  - Purification and characterization of dipeptidase hydrolyzing L-cysteinylglycine
      from radish cotyledon.
AB  - Dipeptidase activity was detected in the soluble fraction of radish (Raphanus
      sativus L.) cotyledon, and the purified enzyme had a specific activity of 7.32
      nkat/mg protein for hydrolyzing L-cysteinylglycine. The dipeptidase was found to
      be a hexameric metalloenzyme, composed of homological 55 kDa-subunits. This is
      the first glutathione catabolism-related dipeptidase isolated from higher plants.

PMID- 18071264
TI  - Lithospermi radix extract inhibits histamine release and production of
      inflammatory cytokine in mast cells.
AB  - Lithospermi radix (LR, Borraginaceae, the root of Lithospermum erythrorhizon
      Siebold. et Zuccarinii) is used in herbal medicine to treat such conditions as
      eczema, skin burns and frostbite. This study investigates the effects of LR on
      the anti-allergy mechanism. LR inhibited the release of histamine from rat
      peritoneal mast cells by compound 48/80 in a dose-dependent manner. LR orally
      administered at 6.59 mg/100 g also inhibited the anti-DNP IgE-induced passive
      cutaneous anaphylaxis reaction. LR inhibited the PMA plus A23187-induced increase
      in IL-6, IL-8, and TNF-alpha expression in HMC-1 cells. In addition, LR also
      inhibited nuclear factor-kappa B (NF-kappaB) activation and I kappaB-alpha
      degradation. These results show that LR had an inhibitory effect on the atopic
      allergic reaction. Furthermore, the in vivo and in vitro anti-allergic effect of
      LR suggests possible therapeutic applications of this agent for inflammatory
      allergic diseases.

PMID- 18071265
TI  - Enhanced bioavailability of soy isoflavones by complexation with beta
      cyclodextrin in rats.
AB  - In order to improve the solubility and bioavailability of a soy isoflavone
      extract (IFE), inclusion complexes (IFE-beta-CD) of the isoflavone extract with
      beta-cyclodextrin (beta-CD) were prepared and studied for their solubility and
      bioavailability. The aqueous solubility of the complexes of IFE with beta-CD (2.0
      mg/ml) was about 26 times that of IFE itself (0.076 mg/ml). The same dosages of
      IFE and IFE-beta-CD were orally administered to SD rats (Sprague-Dawley) on an
      isoflavone glycoside (IFG) basis (daidzin, genistin and glycitin), and the plasma
      concentrations of daidzein, genistein and glycitein were measured over time to
      estimate the average AUC (area under the plasma concentration versus time curve)
      of the isoflavones. After the oral administration, the AUC values for daidzein,
      genistein and glycitein were 340, 11 and 28 microg x min/ml, respectively. In
      contrast, the respective AUC values after the administration of IFE-beta-CD were
      430, 20 and 48 microg x min/ml. The bioavailability of daidzein in IFE-beta-CD
      was increased to 126% by the formation of inclusion complexes with beta-CD,
      compared with that in IFE. Furthermore, the bioavailability of genistein and
      glycitein in IFE-beta-CD formulation was significantly higher by up to 180% and
      170%, respectively, compared with that of IFE p=0.008 and p=0.028, respectively).
      These results show that the absorption of IFE could be improved by the
      complexation of IFE with beta-CD (IFE-beta-CD).

PMID- 18071266
TI  - Effects of excess biotin administration on the growth and urinary excretion of
      water-soluble vitamins in young rats.
AB  - To determine the effects of excess biotin administration on growth and water
      soluble vitamin metabolism, weaning rats were fed on a 20% casein diet containing
      0.00002% biotin, or same diet with 0.04, 0.08, 0.10, 0.20, 0.50, 0.80 or 1.0%
      added biotin for 28 days. More than 0.08% biotin administration decreased the
      food intake and body weight gain compared with the levels in control rats. An
      accumulation of biotin in such tissues as the liver, brain and kidney increased
      in a dose-dependent manner, and the both bound and free biotin contents in the
      liver also increased in a dose-dependent manner. An excess administration of
      biotin did not affect the urinary excretion of other water-soluble vitamins,
      suggesting no effect on the metabolism of other water-soluble vitamins. The
      results of the food intake and body weight gain indicated that the lowest
      observed adverse effect level for young rats was 79.2 mg/kg body weight/day,
      while the no observed adverse effect level was 38.4 mg/kg/day. These results
      suggested immediately setting a tolerable upper intake level for biotin.

PMID- 18071267
TI  - Superoxide dismutase enhanced the formation of hydroxyl radicals in a reaction
      mixture containing xanthone under UVA irradiation.
AB  - To clarify the effect of superoxide dismutase (SOD) on the formation of hydroxyl
      radical in a standard reaction mixture containing 15 microM of xanthone, 0.1 M of
      5,5-dimethyl-1-pyrroline N-oxide (DMPO), and 45 mM of phosphate buffer (pH 7.4)
      under UVA irradiation, electron paramagnetic resonance (EPR) measurements were
      performed. SOD enhanced the formation of hydroxyl radicals. The formation of
      hydroxyl radicals was inhibited on the addition of catalase. The rate of hydroxyl
      radical formation also slowed down under a reduced oxygen concentration, whereas
      it was stimulated by disodium ethylenediaminetetraacetate (EDTA) and
      diethyleneaminepentaacetic acid (DETAPAC). Above findings suggest that O(2),
      H(2)O(2), and iron ions participate in the reaction. SOD possibly enhances the
      formation of the hydroxyl radical in reaction mixtures of photosensitizers that
      can produce O(2)(-.).

PMID- 18071268
TI  - Cloning of the gene cluster responsible for biosynthesis of KS-505a (longestin),
      a unique tetraterpenoid.
AB  - KS-505a (longestin), produced by Streptomyces argenteolus, has a unique structure
      that consists of a tetraterpene (C40) skeleton, to which a 2-O-methylglucuronic
      acid and an o-succinyl benzoate moiety are attached. It is a novel inhibitor of
      calmodulin-dependent cyclic-nucleotide phosphodiesterase, which is representative
      of a potent anti-amnesia drug. As a first step to understanding the biosynthetic
      machinery of this unique and pharmaceutically useful compound, we cloned a KS505a
      biosynthetic gene cluster. First we searched for a gene encoding octaprenyl
      diphosphates, which yielded a C40 precursor by PCR, and four candidate genes were
      obtained. Among these, one was confirmed to have the expected enzyme activity by
      recombinant enzyme assay. On the basis of an analysis of the flanking regions of
      the gene, a putative KS-505a biosynthetic gene cluster consisting of 24 ORFs was
      judged perhaps to be present on a 28-kb DNA fragment. A gene disruption
      experiment was also employed to confirm that the cluster indeed participated in
      KS-505a biosynthesis. This is believed to be the first report detailing the gene
      cluster of a cyclized tetraterpenoid.

PMID- 18071269
TI  - Genetic interaction between the ero1-1 and leu2 mutations in Saccharomyces
      cerevisiae.
AB  - The conditional ero1-1 mutant, deficient in the ER-localized PDI oxidase Ero1p,
      is blocked in disulfide bond formation under restrictive conditions, such as high
      temperature, lack of oxygen, or high concentrations of membrane-permeant thiols.
      Previous studies of the physiological consequences of the ero1-1 mutation were
      carried out in a leu2 mutant. The ero1-1 leu2 strain does not grow in standard
      synthetic complete medium at 30 degrees C, a defect that can be remedied by
      increasing the L-leucine concentration in the medium or by transforming the ero1
      1 leu2 strain with the LEU2 wild-type allele. In addition, the LEU2 gene can
      partially complement the growth impairment at 37 degrees C of the ero1-1 leu2
      mutant. The leucine transporter Bap2p exhibits a dramatic decrease in stability
      in an ero1-1 strain, which may account for the pronounced leucine demand observed
      in the ero1-1 leu2 mutant.

PMID- 18071270
TI  - Relative and absolute configuration of antitumor agent SW-163D.
AB  - Our interest on engineering non-ribosomal synthetase responsible for SW-163
      biosynthesis prompted us to determine the relative and absolute configuration of
      antitumor cyclic depsipeptide SW-163s. We first isolated and identified SW-163
      homologs D, F and G as known compounds UK-63598, UK-65662 and UK-63052,
      respectively. Both enantiomers of the unusual constitutive amino acid, N
      methylnorcoromic acid, were synthesized in chiral forms starting from (R)- and
      (S)-1,2-propanediol. The hydrolyzate of SW-163D, a major constituent of this
      family, was converted with Marfey's reagent, 1-fluoro-2,4-dinitrophenyl-5-L
      alanine-amide (L-FDAA), and the resulting mixture of amino acid derivatives was
      subjected to an LC/MS analysis. Compared with authentic samples, the analytical
      data unambiguously show that SW-163D consisted of L-Ala, D-Ser and (1S, 2S)-N
      methylnorcoronamic acid. The remaining stereochemistry of the N-methylcysteine
      moieties was determined from NOE data.

PMID- 18071271
TI  - Effect of dietary epigallocatechin-3-gallate on cytochrome P450 2E1-dependent
      alcoholic liver damage: enhancement of fatty acid oxidation.
AB  - This study was designed to determine whether dietary epigallocatechin-3-gallate
      (EGCG), the most abundant catechin polyphenol in green tea, can protect the liver
      from cytochrome P450 2E1 (CYP2E1)-dependent alcoholic liver damage. Compared with
      an ethanol group, when EGCG was present in the ethanol diet, the formation of a
      fatty liver was significantly reduced and the serum aspartate transaminase (AST)
      and alanine transaminase (ALT) levels were much lower. Ethanol treatment
      significantly elevated hepatic CYP2E1 expression while simultaneously reducing
      hepatic phospho-acetyl CoA carboxylase (p-ACC) and carnitine palmitoyl
      transferase 1 (CPT-1) levels. While EGCG markedly reversed the effect of ethanol
      on hepatic p-ACC and CPT-1 levels, it had no effect on the ethanol-induced
      elevation in CYP2E1 expression. EGCG prevents ethanol-induced hepatotoxicity and
      inhibits the development of a fatty liver. These effects were associated with
      improvements in p-ACC and CPT-1 levels. The use of EGCG might be useful in
      treating patients with an alcoholic fatty liver.

PMID- 18071272
TI  - First stereoselective synthesis of meso-secoisolariciresinol and comparison of
      its biological activity with (+) and (-)-secoisolariciresinol.
AB  - The first stereoselective synthesis of meso-secoisolariciresinol is reported. A
      comparison of the cytotoxic and immunosuppressive activity between meso
      secoisolariciresinol and optically active secoisolariciresinols was similarly
      performed for the first time. Both enantiomers of secoisolariciresinol
      accelerated IgM production, although meso-secoisolariciresinol did not affect IgM
      production. Only meso-secoisolariciresinol showed cytotoxic activity.

PMID- 18071273
TI  - Free-radical scavenging activity of submerged mycelium extracts from higher
      basidiomycetes mushrooms.
AB  - Twenty-four Basidiomycetes strains were evaluated to determine their free-radical
      scavenging capacity in submerged cultivation. The scavenging capacity of the
      extracts varied from 1 to 85% depending on the mushroom species, solvent used,
      and concentration. A calculation of EC(50) of extracts from several wood-rotting
      Basidiomycetes showed high scavenging abilities at low effective concentration.

PMID- 18071274
TI  - Negative relationship between morphine analgesia and P-glycoprotein expression
      levels in the brain.
AB  - It is known that opioid analgesics given systemically have limited distribution
      into the brain because of their interaction with P-glycoprotein (P-gp), an ATP
      dependent efflux pump acting at the blood-brain barrier (BBB). We previously
      found that morphine and fentanyl showed higher analgesic potencies in P-gp
      deficient mice compared with those in wild-type mice, suggesting that their
      analgesic effects are considerably dependent on P-gp expression. In this study,
      we focused on individual differences in the analgesic effectiveness of morphine,
      in cortical P-gp expression, and in basal P-gp ATPase activity in male ICR mice.
      We found that there were 3- to 10-fold differences between the magnitude of
      morphine analgesia (3 mg/kg, s.c.; tail-pinch method) in mice. Furthermore, there
      was a significant negative correlation between morphine's analgesic effects and
      individual P-gp expression in the cortex as estimated by western blot analysis.
      In addition, basal P-gp ATPase activities in isolated membrane preparations of
      brain capillary endothelial cells (BCECs) were negatively correlated with the
      magnitude of the analgesic effect of morphine. These results indicate that the
      individual differences in morphine analgesia may be due to some functional or
      quantitative differences in individual P-gp in BCECs, acting at the BBB.

PMID- 18071275
TI  - Assessment of cerebrovascular reserve before and after STA-MCA bypass surgery by
      SPECT and SPM analysis.
AB  - OBJECTIVE: The purpose of this study was to objectively assess the efficacy of
      superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery
      using Technetium (Tc)-99m-ethyl cysteinate dimer (ECD) single photon emission
      computed tomography (SPECT) in patients who underwent STA-MCA bypass surgery.
      MATERIALS AND METHODS: Brain perfusion SPECT images obtained at baseline and
      after the administration of acetazolamide were reconstructed using statistical
      parametric mapping in 23 patients, both before and after STA-MCA bypass surgery.
      The clinical outcomes of the surgery were also recorded and compared with the
      hemodynamic changes. A voxel with an uncorrected p-value of less than 0.001 was
      considered to be statistically significant. RESULTS: SPECT images of the
      territory supplied by the bypass graft showed an increase in both cerebrovascular
      flow and reserve at baseline, and the increase was significantly higher following
      the administration of acetazolamide. All patients showed improvement of clinical
      symptoms and increased blood flow to the left temporal, parietal, and frontal
      cortices as well as the thalamus. CONCLUSION: Brain SPECT effectively and
      objectively demonstrated the improved outcomes of STA-MCA bypass surgery, and
      thus may be used in postoperative analyses.

PMID- 18071276
TI  - A correlation between the severity of lung lesions on radiographs and clinical
      findings in patients with severe acute respiratory syndrome.
AB  - OBJECTIVE: The purpose of this study was to quantify lesions on chest radiographs
      in patients with severe acute respiratory syndrome (SARS) and analyze the
      severity of the lesions with clinical parameters. MATERIALS AND METHODS: Two
      experienced radiologists reviewed chest radiographs of 28 patients with SARS.
      Each lung was divided into upper, middle, and lower zones. A SARS-related lesion
      in each zone was scored using a four-point scale: zero to three. The mean and
      maximal radiographic scores were analyzed statistically to determine if the
      scorings were related to the laboratory data and clinical course. RESULTS:
      Forward stepwise multiple linear regression showed that the mean radiographic
      score correlated most significantly with the number of hospitalized days (p <
      0.001). The second most significant factor was the absolute lymphocyte count (p <
      0.001) and the third most significant factor was the number of days of intubation
      (p = 0.025). The maximal radiographic score correlated best with the percentage
      of lymphocytes in a leukocyte count (p < 0.001), while the second most
      significant factor was the number of hospitalized days (p < 0.001) and the third
      most significant factor was the absolute lymphocyte count (p = 0.013). The mean
      radiographic scores of the patients who died, with comorbidities and without a
      comorbidity were 11.1, 6.3 and 2.9, respectively (p = 0.032). The corresponding
      value for maximal radiographic scores were 17.7, 9.7 and 6.0, respectively (p =
      0.033). CONCLUSION: The severity of abnormalities quantified on chest radiographs
      in patients with SARS correlates with the clinical parameters.

PMID- 18071277
TI  - Targeted ultrasound for MR-detected lesions in breast cancer patients.
AB  - OBJECTIVE: To investigate the usefulness of targeted ultrasound (US) in the
      identification of additional suspicious lesions found by magnetic resonance (MR)
      imaging in breast cancer patients and the changes in treatment based on the
      identification of the lesions by the use of targeted US. MATERIALS AND METHODS:
      One-hundred forty nine patients who underwent breast MR imaging for a
      preoperative evaluation of breast cancer between January 2002 and July 2004 were
      included in the study. We searched all cases for any additional lesions that were
      found initially by MR imaging and investigated the performance of targeted US in
      identifying the lesions. We also investigated their pathological outcomes and
      changes in treatment as a result of lesion identification. RESULTS: Of the 149
      patients with breast cancer, additional suspicious lesions were detected with MR
      imaging in 62 patients (42%). Of the 69 additional lesions found in those 62
      patients, 26 (38%) were confirmed as cancers by histology. Thirty-eight lesions
      in 31 patients were examined with targeted US and were histologically revealed as
      cancers in 18 (47%), high risk lesions in two (5%), benign lesions in 15 (39%),
      and unidentified lesions in three (8%). The cancer rate was statistically higher
      in lesions with a US correlate than in lesions without a US correlate (p =
      0.028). Of 31 patients, the surgical plan was altered in 27 (87%). The use of
      targeted US justified a change in treatment for 22 patients (81%) and misled five
      patients (19%) into having an unnecessary surgical excision. CONCLUSION: Targeted
      US can play a useful role in the evaluation of additional suspicious lesions
      detected by MR imaging in breast cancer patients, but is limited in lesions
      without a US correlate.

PMID- 18071278
TI  - Diagnostic performance of CT colonography for the detection of colorectal polyps.
AB  - OBJECTIVE: To investigate the diagnostic value of CT colonography for the
      detection of colorectal polyps. MATERIALS AND METHODS: From December 2004 to
      December 2005, 399 patients underwent CT colonography and follow-up conventional
      colonoscopy. We excluded cases of advanced colorectal cancer. We retrospectively
      analyzed the CT colonography findings and follow-up conventional colonoscopy
      findings of 113 patients who had polyps more than 6 mm in diameter. Radiologists
      using 3D and 2D computer generated displays interpreted the CT colonography
      images. The colonoscopists were aware of the CT colonography findings before the
      procedure. RESULTS: CT colonography detected 132 polyps in 107 of the 113
      patients and conventional colonoscopy detected 114 colorectal polyps more than 6
      mm in diameter in 87 of the 113 patients. The sensitivity of CT colonography
      analyzed per polyp was 91% (41/45) for polyps more than 10 mm in diameter and 89%
      (101/114) for polyps more than 6 mm in diameter. Thirteen polyps were missed by
      CT colonography and were detected on follow-up conventional colonoscopy.
      CONCLUSION: CT colonography is a sensitive diagnostic tool for the detection of
      colorectal polyps and adequate bowel preparation, optimal bowel distention and
      clinical experience are needed to reduce the rate of missing appropriate lesions.

PMID- 18071279
TI  - The sentinel clot sign: a useful CT finding for the evaluation of intraperitoneal
      bladder rupture following blunt trauma.
AB  - OBJECTIVE: To evaluate the frequency and relevance of the "sentinel clot" sign on
      CT for patients with traumatic intraperitoneal bladder rupture in a retrospective
      study. MATERIALS AND METHODS: During a recent 42-month period, 74 consecutive
      trauma patients (45 men, 29 women; age range, 12-84 years; mean age, 50.8 years)
      with gross hematuria were examined by the use of intravenous contrast-enhanced CT
      of the abdomen and pelvis, followed by retrograde cystography. Contrast-enhanced
      CT scanning was performed by using a helical CT scanner. CT images were
      retrospectively reviewed in consensus by two radiologists. The CT findings
      including the sentinel clot sign, pelvic fracture, traumatic injury to other
      abdominal viscera, and the degree of intraperitoneal free fluid were assessed and
      statistically analyzed using the two-tailed x(2) test. RESULTS: Twenty of the 74
      patients had intraperitoneal bladder rupture. The sentinel clot sign was seen for
      16 patients (80%) with intraperitoneal bladder rupture and for four patients (7%)
      without intraperitoneal bladder rupture (p < 0.001). Pelvic fracture was noted in
      five patients (25%) with intraperitoneal bladder rupture and in 39 patients (72%)
      without intraperitoneal bladder rupture (p < 0.001). Intraperitoneal free fluid
      was found in all patients (100%) with intraperitoneal bladder rupture,
      irrespective of an associated intraabdominal visceral injury, whereas 19 (35%) of
      the 54 patients without intraperitoneal bladder rupture had intraperitoneal free
      fluid (p < 0.001). CONCLUSION: Detection and localization of the sentinel clot
      sign abutting on the bladder dome may improve the accuracy of CT in the diagnosis
      of traumatic intraperitoneal bladder rupture, especially when the patients
      present with gross hematuria.

PMID- 18071280
TI  - Radiological spectrum of hepatic mesenchymal hamartoma in children.
AB  - OBJECTIVE: A hepatic mesenchymal hamartoma is an uncommon benign tumor in
      children and little is known about the spectrum of its radiological features. The
      purpose of this study is to describe the spectrum of radiological features of a
      hepatic mesenchymal hamartoma in children. MATERIALS AND METHODS: Thirteen
      children with a pathologically confirmed hepatic mesenchymal hamartoma (M:F =
      7:6; mean age, 3 years 2 months) were included in our study. Ultrasonography (US)
      was performed in nine patients including color and power Doppler US (n = 7). CT
      scans were performed in all patients. We evaluated the imaging findings of the
      hepatic mesenchymal hamartomas and the corresponding pathological features.
      RESULTS: Each patient had a single tumor (mean diameter: 13 cm [1.8-20 cm]). On
      CT and/or US, four patients (31%) had a "multiseptated cystic tumor", five
      patients (38%) had a "mixed solid and cystic tumor", and four patients (31%) had
      a "solid tumor." The septa of the cystic portion were thin in the multiseptated
      cystic tumors and irregularly thick in the mixed solid and cystic tumors as seen
      on US. On a post-contrast CT scan, solid portions or thick septa of the tumors
      showed heterogeneous enhancement. The amount of hepatocytes was significantly
      different among the three tumor groups according to the imaging spectrum (p =
      0.042). CONCLUSION: A hepatic mesenchymal hamartoma in children can show a wide
      spectrum of radiological features, from a multiseptated cystic tumor to a mixed
      solid and cystic tumor, and even a solid tumor.

PMID- 18071281
TI  - Upper airway volume segmentation analysis using cine MRI findings in children
      with tracheostomy tubes.
AB  - OBJECTIVE: The purpose of this study is to evaluate the airway dynamics of the
      upper airway as depicted on cine MRI in children with tracheotomy tubes during
      two states of airflow through the upper airway. MATERIALS AND METHODS: Sagittal
      fast gradient echo cine MR images of the supra-glottic airway were obtained with
      a 1.5T MRI scanner on seven children with tracheotomy tubes. Two sets of images
      were obtained with either the tubes capped or uncapped. The findings of the cine
      MRI were retrospectively reviewed. Volume segmentation of the cine images to
      compare the airway volume change over time (mean volume, standard deviation,
      normalized range, and coefficient of variance) was performed for the capped and
      uncapped tubes in both the nasopharynx and hypopharynx (Signed Rank Test).
      RESULTS: Graphical representation of the airway volume over time demonstrates a
      qualitative increased fluctuation in patients with the tracheotomy tube capped as
      compared to uncapped in both the nasopharyngeal and hypopharyngeal regions of
      interest. In the nasopharynx, the mean airway volume (capped 2.72 mL, uncapped
      2.09 mL, p = 0.0313), the airway volume standard deviation (capped 0.42 mL,
      uncapped 0.20 mL, p = 0.0156), and the airway volume range (capped 2.10 mL,
      uncapped 1.09 mL, p = 0.0156) were significantly larger in the capped group of
      patients. In the hypopharynx, the airway volume standard deviation (capped 1.54
      mL, uncapped 0.67 mL, p = 0.0156), and the airway volume range (capped 6.44 mL,
      uncapped 2.93 mL, p = 0.0156) were significantly larger in the capped tubes. The
      coefficient of variance (capped 0.37, uncapped 0.26, p = 0.0469) and the
      normalized range (capped 1.52, uncapped 1.09, p = 0.0313) were significantly
      larger in the capped tubes. CONCLUSION: There is a statistically significant
      change in airway dynamics in children with tracheotomy tubes when breathing via
      the airway as compared to breathing via the tracheotomy tube.

PMID- 18071282
TI  - Comparison of CT-guided sclerotherapy with using 95% ethanol and 20% hypertonic
      saline for managing simple renal cyst.
AB  - OBJECTIVE: We wanted to compare the efficacies of 95% ethanol and 20% hypertonic
      saline (HS) sclerotherapies that were performed in a single session under CT
      guidance for the management of simple renal cysts. MATERIALS AND METHODS: A
      prospective series of 74 consecutive patients (average age: 57.6 +/- 8.1 years)
      with simple renal cysts were enrolled in this study. They were randomized into
      two groups and 95% ethanol or 20% HS, respectively, corresponding to 25% of the
      aspiration volume, was injected. Treatment success was determined six months
      later with follow-up clinical evaluation and performing ultrasonography. RESULTS:
      The sclerotherapy was accepted as technically successful without major
      complications in all except two patients who were excluded because of a
      communication between the simple renal cyst and the pelvicalyceal collecting
      system. Thirty-six patients in the ethanol group received sclerotherapy with 95%
      ethanol and 36 patients in the HS group underwent sclerotherapy with 20% HS. The
      complete regression ratio of the ethanol group was significantly higher (94%
      versus 72%, respectively) than that of the HS group. There was one patient with
      partial regression in each group. The failure ratio of the ethanol group was
      significantly lower (3% versus 25%, respectively) than that of the HS group.
      CONCLUSION: Ethanol sclerotherapy under CT guidance is a successful and safe
      procedure and it can be used for the treatment of simple renal cysts.
      Sclerotherapy with 95% ethanol is more effective than 20% HS sclerotherapy.
      Sclerotherapy with HS may be an option for patients preferring to undergo a less
      painful treatment procedure.

PMID- 18071283
TI  - The short-term effects of balloon-occluded retrograde transvenous obliteration,
      for treating gastric variceal bleeding, on portal hypertensive changes: a CT
      evaluation.
AB  - OBJECTIVE: We wanted to evaluate the short-term effects of balloon-occluded
      retrograde transvenous obliteration (BRTO) for treating gastric variceal
      bleeding, in terms of the portal hypertensive changes, by comparing CT scans.
      MATERIALS AND METHODS: We enrolled 27 patients who underwent BRTO for gastric
      variceal bleeding and they had CT scans performed just before and after BRTO. The
      pre- and post-procedural CT scans were retrospectively compared by two
      radiologists working in consensus to evaluate the short-term effects of BRTO on
      the subsequent portal hypertensive changes, including ascites, splenomegaly,
      portosystemic collaterals (other than gastrorenal shunt), the gall bladder (GB)
      edema and the intestinal wall edema. Statistical differences were analyzed using
      the Wilcoxon signed rank test and the paired t-test. RESULTS: Following BRTO,
      ascites developed or was aggravated in 22 (82%) of 27 patients and it was
      improved in two patients; the median spleen volumes increased from 438.2 cm(3) to
      580.8 cm(3), and based on a 15% volume change cut-off value, splenic enlargement
      occurred in 15 (56%) of the 27 patients. The development of new collaterals or
      worsening of existing collaterals was not observed in any patient. GB wall edema
      developed or was aggravated in four of 23 patients and this disappeared or
      improved in five; intestinal wall edema developed or was aggravated in nine of 27
      patients, and this disappeared or improved in five. Statistically, we found
      significant differences for ascites and the splenic volumes before and after BRTO
      (p = 0.001 and p < 0.001, respectively) CONCLUSION: Some portal hypertensive
      changes, including ascites and splenomegaly, can be aggravated shortly after
      BRTO.

PMID- 18071284
TI  - Hydatid disease involving some rare locations in the body: a pictorial essay.
AB  - Hydatid disease (HD) is an endemic illness in many countries, and it poses an
      important public health problem that's influenced by peoples' socioeconomic
      status and migration that spreads this disease. Although rare, it may occur in
      any organ or tissue. The most common site is the liver (59-75%), followed in
      frequency by lung (27%), kidney (3%), bone (1-4%) and brain (1-2%). Other sites
      such as the heart, spleen, pancreas and muscles are very rarely affected. Unusual
      sites for this disease can cause diagnostic problems. This pictorial essay
      illustrates various radiological findings of HD in the liver, spleen, kidney,
      pancreas, peritoneal cavity, omentum, adrenal, ovary, lung, mediastinum and
      retroperitoneum. Familiarity with the imaging findings of HD may be helpful in
      making an accurate diagnosis and preventing potential complications.

PMID- 18071285
TI  - Primary extraskeletal mesenchymal chondrosarcoma arising from the pancreas.
AB  - We report here on a case of primary extraskeletal mesenchymal chondrosarcoma that
      arose from the pancreas. A 41-year-old man was evaluated by CT to find the cause
      of his abdominal pain. The CT scans showed a heterogeneously enhancing necrotic
      mass with numerous areas of coarse calcification, and this was located in the
      left side of the retroperitoneal space and involved the body and tail of the
      pancreas. Portal venography via the celiac axis also showed invasion of the
      splenic vein. Following excision of the mass, it was pathologically confirmed to
      be primary extraskeletal mesenchymal chondrosarcoma that arose from the pancreas.

PMID- 18071286
TI  - Imaging findings of central nervous system vasculitis associated with
      Goodpasture's Syndrome: a case report.
AB  - Glomerulonephritis and pulmonary hemorrhage are features of Goodpasture's
      syndrome. Goodpasture's syndrome accompanied with central nervous system (CNS)
      vasculitis is extremely rare. Herein, we report a rare case of CNS vasculitis
      associated with Goodpasture's syndrome in a 34-year-old man, who presented with a
      seizure and sudden onset of right sided weakness. He also had recurrent
      hemoptysis of one month's duration. Goodpasture's syndrome is histologically
      diagnosed by intense linear deposits of IgG along the glomerular basement
      membrane in both renal and lung tissues.

PMID- 18071287
TI  - Pelvic hydatid disease: CT and MRI findings causing sciatica.
AB  - Pelvic masses, especially hydatid disease, rarely present with sciatica (1, 2).
      We present the computed tomography (CT) and the magnetic resonance imaging (MRI)
      findings of a 49-year-old female patient with presacral hydatid disease, who was
      evaluated for her sciatica. We also want to emphasize the importance of assessing
      the pelvis of patients with symptoms and clinical findings that are inconsistent
      and that cannot be satisfactorily explained by the spinal imaging findings.

PMID- 18071288
TI  - Myoepitheliomas of the soft palate: helical CT findings in two patients.
AB  - We describe the enhancement patterns of myoepithelioma in two patients with a
      soft palate mass. In the first case, helical CT revealed a faintly enhancing
      mass. Histologically, the tumor was composed of plasmacytoid cells in a
      background of rich myxoid stroma. Immunostaining for CD34 showed scanty blood
      vessels. In the second case, helical CT revealed an intensely enhancing mass.
      Histologically, the mass was a cellular tumor with fibrous stroma. Immunostaining
      for CD34 also showed frequent blood vessels.

PMID- 18071289
TI  - Hemoperitoneum caused by hepatic necrosis and rupture following a snakebite: a
      case report with rare CT findings and successful embolization.
AB  - We report the computed tomographic and angiographic findings in the case of a
      recently obtained successful clinical outcome after embolization of the hepatic
      artery in the case of a snakebite causing hemoperitoneum associated with hepatic
      necrosis and rupture with active bleeding.

PMID- 18071290
TI  - Intensive conditioning regimen of etoposide (VP-16), cyclophosphamide and
      carmustine (VCB) followed by autologous hematopoietic stem cell transplantation
      for relapsed and refractory Hodgkin's lymphoma.
AB  - Several high-dose therapy regimens are used for autologous hematopoietic stem
      cell transplantation (auto-HSCT) for relapsed and refractory Hodgkin's lymphoma
      (HL) with variable disease response. An intensified regimen of etoposide (VP-16)
      2,400 mg/m(2), cyclophosphamide 7,200 mg/m(2) and carmustine (BCNU) 600 mg/m(2)
      (VCB) pre-auto-HSCT was developed to overcome disease recurrence. A total of 43
      relapsed and refractory HL patients underwent auto-HSCT between January 1992 and
      December 2004. At day 100 there were 37 (86%) complete responses. A total of 40
      patients survived beyond day 100, 14 of whom subsequently relapsed/progressed. At
      a median follow-up of 4.9 years (range 1.5-11.4 years), 26 patients (60%) are
      alive and disease free. Five-year actuarial event-free survival (EFS) was 53%
      (95% CI 35-70%) and median EFS was 5.9 years. Median progression-free and overall
      survivals have not been reached. EFS was reduced with an increasing number of
      prognostic factors (Karnofsky performance status, KPS <90, chemotherapy-resistant
      disease and >or=3 chemotherapy regimens prior to transplant <or=1 vs >or=2;
      P=0.049). Grade III-IV regimen-related toxicity was 9% (n=4). The 1-year
      cumulative incidence of interstitial pneumonitis (IP) was 36%, however only two
      patients died of IP complications. Disease progression was the most common cause
      of death (n=10, 23%). Intensive VCB is an effective and well-tolerated
      preparative regimen for relapsed and refractory HL auto-HSCT.

PMID- 18071291
TI  - Aging of registered stem cell donors: implications for donor recruitment.
AB  - With more than 11 million registered stem cell donors worldwide and limited
      resources for health systems, it seems questionable if investments in ongoing
      donor recruitment are useful. Since there is evidence that transplant outcomes
      are better with younger donors, the age distribution of registered donors is
      highly relevant in this context. One might argue that the usefulness of a donor
      file decreases if there is no new donor recruitment not only as a result of loss
      of donors who reach the age limit for donation but also since those donors who
      remain in the file get older. We established a multivariate model to quantify
      this effect and to estimate the number (designated R) of donors who must be
      recruited annually to keep donor file usefulness constant. The model is applied
      to real data from DKMS German Bone Marrow Donor Center. R exceeds the number of
      donors who reach the age limit by factors up to 7.3. The model can serve as an
      easy-to-use tool for strategic donor registry planning. Our results suggest that
      analyses regarding optimal size of donor registries should also include the age
      distribution of registered donors.

PMID- 18071292
TI  - Durable remission of large B-cell lymphoma transformed from lymphoplasmacytic
      lymphoma/Waldenstrom macroglobulinemia successfully treated with sequential
      immunochemotherapy followed by reduced-intensity allogeneic stem cell
      transplantation.

PMID- 18071294
TI  - Negative and positive allosteric modulators of the P2X(7) receptor.
AB  - BACKGROUND AND PURPOSE: Antagonist effects at the P2X(7) receptor are complex
      with many behaving in a non-competitive manner. In this study, the effects of N
      [2-({2-[(2-hydroxyethyl)amino]ethyl}amino)-5-quinolinyl]-2
      tricyclo[3.3.1.1(3,7)]dec-1-ylacetamide (compound-17) and N (2)-(3,4
      difluorophenyl)-N (1)-[2-methyl-5-(1-piperazinylmethyl)phenyl]glycinamide
      dihydrochloride (GW791343) on P2X(7) receptors were examined and their mechanism
      of action explored. EXPERIMENTAL APPROACH: Antagonist effects were studied by
      measuring agonist-stimulated ethidium accumulation in cells expressing human or
      rat recombinant P2X(7) receptors and in radioligand binding studies. KEY RESULTS:
      Compound-17 and GW791343 were non-competitive inhibitors of human P2X(7)
      receptors. Receptor protection studies using decavanadate and pyridoxalphosphate
      6-azophenyl-2',4'-disulphonic acid (PPADS) showed that neither compound-17 nor
      GW791343 competitively interacted at the ATP binding site and so were probably
      negative allosteric modulators of the P2X(7) receptor. GW791343 prevented the
      slowly reversible blockade of the human P2X(7) receptor produced by compound-17
      and inhibited [(3)H]-compound-17 binding to the P2X(7) receptor suggesting they
      may bind to similar or interacting sites. At rat P2X(7) receptors, compound-17
      was a negative allosteric modulator but the predominant effect of GW791343 was to
      increase agonist responses. Antagonist interaction and radioligand binding
      studies revealed that GW791343 did not interact at the ATP binding site but did
      interact with the compound-17 binding site suggesting that GW791343 is a positive
      allosteric modulator of the rat P2X(7) receptor. CONCLUSIONS: Compound-17 was a
      negative allosteric modulator of human and rat P2X(7) receptors. GW791343 was a
      negative allosteric modulator of the human P2X(7) receptor but at the rat P2X(7)
      receptor its predominant effect was positive allosteric modulation. These
      compounds should provide valuable tools for mechanistic studies on P2X(7)
      receptors.

PMID- 18071293
TI  - A Holy Grail of asthma management: toward understanding how long-acting beta(2)
      adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids.
AB  - There is unequivocal evidence that the combination of an inhaled corticosteroid
      (ICS) -- i.e. glucocorticoid -- and an inhaled long-acting beta(2)-adrenoceptor
      agonist (LABA) is superior to each component administered as a monotherapy alone
      in the clinical management of asthma. Moreover, Calverley and colleagues (Lancet
      2003, 361: 449-456; N Engl J Med 2007, 356: 775-789) reporting for the 'TRial of
      Inhaled STeroids ANd long-acting beta(2)-agonists (TRISTAN)' and 'TOwards a
      Revolution in COPD Health (TORCH)' international study groups also demonstrated
      the superior efficacy of LABA/ICS combination therapies over ICS alone in the
      clinical management of chronic obstructive pulmonary disease. This finding has
      been independently confirmed indicating that the therapeutic benefit of LABA/ICS
      combination therapies is not restricted to asthma and may be extended to other
      chronic inflammatory diseases of the airways. Despite the unquestionable benefit
      of LABA/ICS combination therapies, there is a vast gap in our understanding of
      how these two drugs given together deliver superior clinical efficacy. In this
      article, we review the history of LABA/ICS combination therapies and critically
      evaluate how these two classes of drugs might interact at the biochemical level
      to suppress pro-inflammatory responses. Understanding the molecular basis of this
      fundamental clinical observation is a Holy Grail of current respiratory diseases
      research as it could permit the rational exploitation of this effect with the
      development of new 'optimized' LABA/ICS combination therapies.

PMID- 18071295
TI  - Bretylium abolishes neurotransmitter release without necessarily abolishing the
      nerve terminal action potential in sympathetic terminals.
AB  - BACKGROUND AND PURPOSE: The antidysrhythmic bretylium is useful experimentally
      because it selectively abolishes neurotransmitter release from sympathetic
      peripheral nerve terminals. Its mechanism of action seemed settled, but recent
      results from optical monitoring of single terminals now suggests a new
      interpretation. EXPERIMENTAL APPROACH: Orthograde transport of a dextran
      conjugated Ca(2+) indicator to monitor Ca(2+) in nerve terminals of mouse
      isolated vas deferens with a confocal microscope. In some experiments, local
      neurotransmitter release was detected by monitoring neuroeffector Ca(2+)
      transients (NCTs) in adjacent smooth muscles, a local measure of purinergic
      transmission. Sympathetic terminals were identified with catecholamine
      fluorescence (UV excitation) or post-experiment immunohistochemistry. KEY
      RESULTS: Bretylium (10 microM) abolished NCTs at 60/61 junctions over the course
      of 2 h, indicating effective abolition of neurotransmitter release. However,
      bretylium did not abolish the field stimulus-induced Ca(2+) transient in most
      nerve terminals, but did increase both action potential delay (by 2+/-0.4 ms) and
      absolute refractory period (by 4+/-2 ms). Immunohistochemistry demonstrated that
      85-96% of terminals orthogradely filled with a dextran-conjugated fluorescent
      probe contained Neuropeptide Y (NPY). A formaldehyde-glutaraldehyde-induced
      catecholamine fluorescence (FAGLU) technique was modified to allow sympathetic
      terminals to be identified with a Ca(2+) indicator present. Most terminals
      contained catecholamines (based on FAGLU) or secrete ATP (as NCTs in adjacent
      smooth muscle cells are abolished). CONCLUSIONS AND IMPLICATIONS: Bretylium can
      inhibit neurotransmitter release downstream of Ca(2+) influx without abolishing
      the nerve terminal action potential. Bretylium-induced increases in the absolute
      refractory period permit living sympathetic terminals to be identified.

PMID- 18071296
TI  - Inhibition of matrix metalloproteinases prevents peroxynitrite-induced
      contractile dysfunction in the isolated cardiac myocyte.
AB  - BACKGROUND AND PURPOSE: The potent oxidant peroxynitrite (ONOO(-)) induces
      mechanical dysfunction in the intact heart in part through activation of matrix
      metalloproteinase-2 (MMP-2). This effect may be independent of the proteolytic
      actions of MMPs on extracellular matrix proteins. The purpose of this study was
      to examine the effects of ONOO(-) on contractile function at the level of the
      single cardiac myocyte and whether this includes the action of MMPs. EXPERIMENTAL
      APPROACH: Freshly isolated ventricular myocytes from adult rats were superfused
      with Krebs-Henseleit buffer at 21 degrees C and paced at 0.5 Hz. Contractility
      was measured using a video edge-detector. ONOO(-) or decomposed ONOO(-) (vehicle
      control) were co-infused over 40 min to evaluate the contraction cease time
      (CCT). The effects of ONOO(-) on intracellular [Ca(2+)] were determined in
      myocytes loaded with calcium green-1 AM. MMP-2 activity was measured by gelatin
      zymography. KEY RESULTS: ONOO(-) (30-600 microM) caused a concentration-dependent
      reduction in CCT. Myocytes subjected to 300 microM ONOO(-) had a shorter CCT than
      decomposed ONOO(-) (14.9+1.5 vs 32.2+3.5 min, n=7-8; P<0.05) and showed increased
      MMP-2 activity. The MMP inhibitors doxycycline (100 microM) or PD 166793 (2
      microM) reduced the decline in CCT induced by 300 microM ONOO(-). ONOO(-) caused
      shorter calcium transient cease time and significant alterations in intracellular
      [Ca(2+)] homoeostasis which were partially prevented by doxycycline. CONCLUSIONS
      AND IMPLICATIONS: This is the first demonstration that inhibition of MMPs
      protects the cardiac myocyte from ONOO(-)-induced contractile failure via an
      action unrelated to proteolysis of extracellular matrix proteins.

PMID- 18071297
TI  - alpha(1)-Adrenoceptor antagonists prevent paracetamol-induced hepatotoxicity in
      mice.
AB  - BACKGROUND AND PURPOSE: Paracetamol, a major cause of acute liver failure (ALF)
      represents a significant clinical problem. Adrenoceptor stimulation or antagonism
      can modulate chemical-induced hepatotoxicity. We investigated the role of
      endogenous catecholamines and alpha(1)-adrenoceptors in the development of
      paracetamol- induced hepatotoxicity. EXPERIMENTAL APPROACH: Paracetamol (3.5 mmol
      kg(-1)) was administered to male CD-1 mice, with and without alpha(1)
      adrenoceptor antagonists (prazosin, doxazosin, terazosin and tamsulosin; 35.7
      micromol kg(-1)). Serum transaminases and hepatic glutathione (GSH) levels were
      assessed as markers of hepatic damage. Paracetamol bioactivation was assessed by
      covalent binding, hepatic and urinary conjugate formation and uridine
      glucuronosyltransferase activity. Plasma catecholamines levels and hepatic
      congestion were also analysed. KEY RESULTS: Plasma catecholamine levels were
      significantly elevated 5 h post paracetamol administration. Prazosin prevented
      hepatotoxicity when administered 1 h before a toxic paracetamol insult and
      importantly, when administered up to 1 h post paracetamol injection. Prazosin had
      no effect on paracetamol-induced depletion of hepatic GSH, paracetamol
      bioactivation or paracetamol-induced transcription of defence genes. Paracetamol
      toxicity is associated with marked accumulation of erythrocytes within hepatic
      sinusoids and prazosin completely prevented this accumulation. CONCLUSION AND
      IMPLICATIONS: Paracetamol-induced hepatocellular damage is associated with
      increased circulating catecholamines. alpha(1)-Adrenoceptor antagonists conferred
      complete protection from paracetamol -induced hepatotoxicity. Protection was
      associated with absence of hepatic erythrocyte accumulation. Increased
      catecholamine levels may contribute to the pathophysiology of paracetamol-induced
      hepatotoxicity by compromising hepatic perfusion. Protection against paracetamol
      toxicity by alpha(1) antagonists in mice has implications for therapeutic
      management of patients presenting with paracetamol overdose and ALF.

PMID- 18071298
TI  - Rifampicin exacerbates isoniazid-induced toxicity in human but not in rat
      hepatocytes in tissue-like cultures.
AB  - BACKGROUND AND PURPOSE: Rifampicin has been extensively reported to exacerbate
      the hepatotoxicity of isoniazid in patients with tuberculosis. However, this was
      controversially claimed by previous reports using rat models. This study
      evaluated the effect of rifampicin on isoniazid-induced hepatocyte toxicity by
      using human and rat hepatocytes in tissue-like culture. EXPERIMENTAL APPROACH:
      Hepatocytes in tissue-like gel entrapment were used to examine isoniazid
      toxicity, as shown by cell viability, intracellular glutathione content and
      albumin secretion. For demonstration of the differential effects of rifampicin on
      human and rat hepatocytes, induction by rifampicin of cytochrome P450 (CYP) 2E1,
      a major enzyme associated with isoniazid hepatotoxicity, was detected by 4
      nitrocatechol formation and RT-PCR analysis. KEY RESULTS: Rifampicin (12 microM)
      enhanced isoniazid-induced toxicity in human hepatocytes but not in rat
      hepatocytes. Enhanced CYP 2E1 enzymic activity and mRNA expression were similarly
      detected in human hepatocytes but not in rat hepatocytes. Both rat and human
      hepatocytes in gel entrapment were more sensitive to isoniazid treatment compared
      with the corresponding hepatocytes in a monolayer culture. CONCLUSIONS AND
      IMPLICATIONS: The difference in induction of CYP 2E1 by rifampicin between rat
      and human hepatocytes accounted for the difference in exacerbation of isoniazid
      hepatocyte toxicity by rifampicin, with more significant toxicity in gel
      entrapment than in monolayer cultures. Thus, human hepatocytes in tissue-like
      cultures (gel entrapment) could be an effective model for hepatotoxicity research
      in vitro, closer to the in vivo situation.

PMID- 18071299
TI  - Orphan GPCR research.
AB  - Orphan G protein-coupled receptors (GPCRs) are receptors lacking endogenous
      ligands. Found by molecular biological analyses, they became the roots of reverse
      pharmacology, in which receptors are attempted to be matched to potential
      transmitters. Later, when high-throughput screening technology was applied to
      reverse pharmacology, dozens of orphan GPCRs became deorphanized. Furthermore,
      novel neuropeptides were discovered. This review retraces the history of the
      orphan GPCRs and of the discoveries of their endogenous ligands, it also
      discusses the difficulties that the search for new ligands is presently
      encountering.

PMID- 18071300
TI  - Role of the NO/cGMP/K(ATP) pathway in the protective effects of sildenafil
      against ethanol-induced gastric damage in rats.
AB  - BACKGROUND AND PURPOSE: Sildenafil is a selective inhibitor of cGMP-specific
      phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents
      indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels
      (K(ATP)) is involved in gastric defence. Our objective was to evaluate the role
      of the NO/cGMP/K(ATP) pathway in the protective effects of sildenafil against
      ethanol-induced gastric damage. EXPERIMENTAL APPROACH: Rats were treated with L
      NAME (1 or 3 mg kg(-1), i.p.) or with L-arginine (200 mg kg(-1), i.p.) + L-NAME
      (3 mg kg(-1), i.p.), the guanylate cyclase inhibitor, ODQ (10 mg kg(-1), i.p.),
      glibenclamide (0.1, 0.3, 1 or 3 mg kg(-1), i.p.) or with glibenclamide (1 mg kg(
      1), i.p.) + diazoxide (3 mg kg(-1), i.p.). After thirty minutes, the rats
      received sildenafil (1 mg kg(-1), by gavage), followed by intragastric
      instillation of absolute ethanol (4 ml kg(-1)) to induce gastric damage. One hour
      later, gastric damage (haemorrhagic or ulcerative lesions) was measured with a
      planimetry programme. Samples of stomach were also taken for histopathological
      assessment and for assays of tissue glutathione and haemoglobin. KEY RESULTS:
      Sildenafil significantly reduced ethanol-induced gastric damage in rats. L-NAME
      alone, without L-arginine, significantly reversed the protection afforded by
      sildenafil. Inhibition of guanylate cyclase by ODQ completely abolished the
      gastric protective effect of sildenafil against ethanol-induced gastric damage.
      Glibenclamide alone reversed sildenafil's gastric protective effect. However,
      glibenclamide plus diazoxide did not alter the effects of sildenafil.
      CONCLUSIONS: Sildenafil had a protective effect against ethanol-induced gastric
      damage through the activation of the NO/cGMP/K(ATP) pathway.

PMID- 18071301
TI  - Cannabinoid receptors and the regulation of bone mass.
AB  - A functional endocannabinoid system is present in several mammalian organs and
      tissues. Recently, endocannabinoids and their receptors have been reported in the
      skeleton. Osteoblasts, the bone forming cells, and osteoclasts, the bone
      resorbing cells, produce the endocannabinoids anandamide and 2
      arachidonoylglycerol and express CB2 cannabinoid receptors. Although CB2 has been
      implicated in pathological processes in the central nervous system and peripheral
      tissues, the skeleton appears as the main system physiologically regulated by
      CB2. CB2-deficient mice show a markedly accelerated age-related bone loss and the
      CNR2 gene (encoding CB2) in women is associated with low bone mineral density.
      The activation of CB2 attenuates ovariectomy-induced bone loss in mice by
      restraining bone resorption and enhancing bone formation. Hence synthetic CB2
      ligands, which are stable and orally available, provide a basis for developing
      novel anti-osteoporotic therapies. Activation of CB1 in sympathetic nerve
      terminals in bone inhibits norepinephrine release, thus balancing the tonic
      sympathetic restrain of bone formation. Low levels of CB1 were also reported in
      osteoclasts. CB1-null mice display a skeletal phenotype that is dependent on the
      mouse strain, gender and specific mutation of the CB1 encoding gene, CNR1.

PMID- 18071302
TI  - Inhibition of late sodium current to reduce electrical and mechanical dysfunction
      of ischaemic myocardium.
AB  - This commentary on the review by DA Saint in the current issue of the British
      Journal of Pharmacology focuses on the pathological role of late I(Na) in the
      heart, the evidence supporting inhibition of late I(Na) as a therapeutic target
      in ischaemic heart disease, and the therapeutic applications and challenges for
      development of new late I(Na) inhibitors. Recent reports from a large clinical
      outcome trial (MERLIN) of ranolazine, a drug known to inhibit late I(Na),
      indicated that it was safe and reduced recurrent ischaemia and arrhythmic
      activity. In combination with other results indicating that inhibition of late
      I(Na) reduces ischaemia, myocardial Ca(2+) overload, and electrical and
      mechanical dysfunction when late I(Na) is increased, the new clinical trial
      results suggest that reduction of cardiac late I(Na) is safe and therapeutically
      beneficial.

PMID- 18071304
TI  - Protein kinase A-mediated phosphorylation of the NF2 tumor suppressor protein
      merlin at serine 10 affects the actin cytoskeleton.
AB  - Mutations in the neurofibromatosis 2 tumor suppressor gene (NF2) encoding merlin
      (moesin-ezrin-radixin like-protein) induce tumors of the nervous system. Merlin
      localizes to the cell membrane where it links the actin cytoskeleton to membrane
      proteins. Cell proliferation is regulated by merlin in many cell types, but
      merlin's tumor suppressor function still remains unclear. Phosphorylation has
      been suggested to regulate merlin's activity. The C-terminal serine 518 is
      phosphorylated both by p21-activated kinases (PAKs) and protein kinase A (PKA).
      In this work, we identify a novel PKA phosphorylation site, serine 10, in the N
      terminus of merlin. We show that a non-phosphorylatable form of serine 10 (S10A)
      affects cellular morphology. Regulation of this site also influences actin
      cytoskeleton organization and dynamics in vivo, as merlin S10A reduces the amount
      of cellular F-actin and merlin S10D stabilizes F-actin filaments. By using a
      wound-healing assay and live cell imaging, we demonstrate that dephosphorylation
      of serine 10 leads to defects in migration, possibly through altered ability of
      the cells to form lamellipodia. This study suggests a role for merlin in
      mediating PKA-induced changes of the actin cytoskeleton.

PMID- 18071305
TI  - Orphan nuclear receptor estrogen-related receptor-beta suppresses in vitro and in
      vivo growth of prostate cancer cells via p21(WAF1/CIP1) induction and as a
      potential therapeutic target in prostate cancer.
AB  - Recent studies indicate that estrogen-related receptors (ERRs) are involved in
      similar estrogen receptor (ER) regulatory pathways and play roles in energy and
      lipid metabolism. Here, we analysed the functional role of ERRbeta in prostate
      cancer cell growth regulation in an androgen-sensitive and androgen-insensitive
      prostate cancer cell lines. ERRbeta was expressed in normal human prostates, but
      exhibited a reduced expression in prostate cancer lesions. Stable ERRbeta
      expression suppressed significantly cell proliferation and tumorigenicity of
      LNCaP and DU145 cells, accompanied by an S-phase suppression and increased p21
      expression. Reporter and chromatin immunoprecipitation assays showed that ERRbeta
      could directly transactivate p21 gene promoter, which could be further enhanced
      by peroxisome proliferator-activated receptor-gamma coactivator-1alpha.
      Truncation analysis showed that ERRbeta-mediated p21 transactivation and prostate
      cancer cell growth inhibition required intact DNA-binding domain and AF2 domains
      in ERRbeta. Interestingly, ERRbeta displayed a cell cycle associated
      downregulated expression pattern in ERRbeta-transduced and non-transduced cells.
      Finally, we showed that ERRbeta-mediated growth inhibition could be potentiated
      by an ERRbeta/gamma agonist DY131. Knockdown of ERRbeta by RNA interference could
      reduce the DY131-induced growth inhibition in prostate cancer cells. Taken
      together, our findings indicate that ERRbeta performs a tumor suppressing
      function in prostate cancer cells, and targeting ERRbeta could be a potential
      therapeutic strategy for prostate cancer.

PMID- 18071303
TI  - The cardiac persistent sodium current: an appealing therapeutic target?
AB  - The sodium current in the heart is not a single current with a mono-exponential
      decay but rather a mixture of currents with different kinetics. It is not clear
      whether these arise from distinct populations of channels, or from modulation of
      a single population. A very slowly inactivating component, [(INa(P))] I(Na(P)) is
      usually about 1% of the size of the peak transient current [I(Na(T))], but is
      enhanced by hypoxia. It contributes to Na(+) loading and cellular damage in
      ischaemia and re-perfusion, and perhaps to ischaemic arrhythmias. Class I
      antiarrhythmic agents such as flecainide, lidocaine and mexiletine generally
      block I(NA(P)) more potently than block of I(Na(T)) and have been used clinically
      to treat LQT3 syndrome, which arises because mutations in SCN5A produce defective
      inactivation of the cardiac sodium channel. The same approach may be useful in
      some pathological situations, such as ischaemic arrhythmias or diastolic
      dysfunction, and newer agents are being developed with this goal. For example,
      ranolazine blocks I(Na(P)) about 10 times more potently than I(Na(T)) and has
      shown promise in the treatment of angina. Alternatively, the combination of
      I(Na(P)) block with K(+) channel block may provide protection from the induction
      of Torsades de Pointe when these agents are used to treat atrial arrhythmias (eg
      Vernakalant). In all of these scenarios, an understanding of the role of I(Na(P))
      in cardiac pathophysiology, the mechanisms by which it may affect cardiac
      electrophysiology and the potential side effects of blocking I(Na(P)) in the
      heart and elsewhere will become increasingly important.

PMID- 18071306
TI  - Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in
      adult T-cell leukemia.
AB  - Adult T-cell leukemia (ATL) is a mature CD4+ T-cell malignancy etiologically
      associated with human T-cell leukemia virus type 1 (HTLV-1). Primary ATL cells
      frequently express CCR4 at high levels. Since HTLV-1 Tax does not induce CCR4
      expression, transcription factor(s) constitutively active in ATL may be
      responsible for its strong expression. We identified an activator protein-1 (AP
      1) site in the CCR4 promoter as the major positive regulatory element in ATL
      cells. Among the AP-1 family members, Fra-2, JunB and JunD are highly expressed
      in fresh primary ATL cells. Consistently, the Fra-2/JunB and Fra-2/JunD
      heterodimers strongly activated the CCR4 promoter in Jurkat cells. Furthermore,
      Fra-2 small interfering RNA (siRNA) or JunD siRNA, but not JunB siRNA,
      effectively reduced CCR4 expression and cell growth in ATL cells. Conversely, Fra
      2 or JunD overexpression promoted cell growth in Jurkat cells. We identified 49
      genes, including c-Myb, BCL-6 and MDM2, which were downregulated by Fra-2 siRNA
      in ATL cells. c-Myb, BCL-6 and MDM2 were also downregulated by JunD siRNA. As Fra
      2, these proto-oncogenes were highly expressed in primary ATL cells but not in
      normal CD4+ T cells. Collectively, aberrantly expressed Fra-2 in association with
      JunD may play a major role in CCR4 expression and oncogenesis in ATL.

PMID- 18071307
TI  - MT1-MMP is required for efficient tumor dissemination in experimental metastatic
      disease.
AB  - Membrane-type I matrix metalloproteinase (MT1-MMP) is associated with multiple
      forms of cancer including mammary cancer. To directly evaluate the significance
      of MT1-MMP expression in tumor progression and metastasis using a genetically
      induced cancer model, we crossed MT1-MMP-deficient mice to MMTV-polyoma virus
      middle T-antigen (PyMT) mice. Expression of PyMT in the MT1-MMP-deficient
      background consistently resulted in hyperplasia of the mammary gland as seen in
      wild-type PyMT littermates. Following orthotopic transplantation of PyMT+ glands
      into the cleared mammary fat pad of syngeneic recipient mice, MT1-MMP-deficient
      tumors were palpable earlier than wild-type tumors. Moreover, MT1-MMP-deficient
      tumors grew to the experimental end point size quicker than control tumors, but
      demonstrated markedly reduced ability to metastasize to the lungs of recipient
      mice. Accordingly, MT1-MMP-deficient mice displayed an overall reduction in
      metastasis count of 50%. MT1-MMP was expressed solely in the stroma of PyMT
      induced tumors and those metastatic nodules that formed in the lungs were devoid
      of MT1-MMP expression. Stromal fibroblasts isolated from MT1-MMP-deficient tumors
      did not degrade type I collagen suggesting that efficient dissemination of tumor
      cells is dependent on stromal cell remodeling of the tumor environment. The data
      demonstrate directly that MT1-MMP-mediated proteolysis by stromal cells is
      important in the metastatic process.

PMID- 18071308
TI  - The FLT3 inhibitor PKC412 exerts differential cell cycle effects on leukemic
      cells depending on the presence of FLT3 mutations.
AB  - PKC412 is a staurosporine derivative that inhibits several protein kinases
      including FLT3, and is highly anticipated as a novel therapeutic agent for acute
      myeloblastic leukemia (AML) carrying FLT3 mutations. In this study, we show that
      PKC412 exerts differential cell cycle effects on AML cells depending on the
      presence of FLT3 mutations. PKC412 elicits massive apoptosis without markedly
      affecting cell cycle patterns in AML cell lines with FLT3 mutations (MV4-11 and
      MOLM13), whereas it induces G2 arrest but not apoptosis in AML cell lines without
      FLT3 mutations (THP-1 and U937). In MV4-11 and MOLM13 cells, PKC412 inactivates
      Myt-1 and activates CDC25c, leading to the activation of CDC2. Activated CDC2
      phosphorylates Bad at serine-128 and facilitates its translocation to the
      mitochondria, where Bad triggers apoptosis. In contrast, PKC412 inactivates CDC2
      by inducing serine-216 phosphorylation and subsequent cytoplasmic sequestration
      of CDC25c in THP-1 and U937 cells. As a result, cells are arrested in the G2
      phase of the cell cycle, but do not undergo apoptosis because Bad is not
      activated. The FLT3 mutation-dependent differential cell cycle effect of PKC412
      is considered an important factor when PKC412 is combined with cell cycle
      specific anticancer drugs in the treatment of cancer and leukemia.

PMID- 18071309
TI  - BCR-ABL oncogenic transformation of NIH 3T3 fibroblasts requires the IL-3
      receptor.
AB  - Oncogenic transformation of hematopoietic cells by the Bcr-Abl oncoprotein
      directly involves the activation Jak2 tyrosine kinase and the Stat5 transcription
      factor. Both proteins are normally linked to the interleukin (IL)-3/granulocyte
      macrophage colony-stimulating factor receptors for growth and survival. Since
      fibroblastic cells are not targets of BCR-ABL-induced oncogenesis, we determined
      whether forced expression of the IL-3 receptor would allow oncogenic
      transformation of NIH 3T3 fibroblasts known to be resistant to transformation by
      BCR-ABL. NIH 3T3 cells transduced with the human IL-3 receptor alpha and beta
      chains were highly susceptible to oncogenic transformation by expression of BCR
      ABL. Forced expression of both receptor chains but not either one alone allowed
      efficient foci formation of NIH 3T3 cells expressing BCR-ABL (triple positive
      cells), and these cells formed colonies in soft agar, whereas BCR-ABL+ NIH 3T3
      cells lacking IL-3 receptor expression did not. Signaling studies indicate that
      the BCR-ABL/IL-3 receptor+ NIH 3T3 cells utilize the Gab2/PI-3 kinase pathway
      activated by Jak2, and the Stat5 pathway activated separately by Bcr-Abl, whereas
      BCR-ABL+ NIH 3T3 cells lacking the IL-3 receptor do not utilize the Jak2 pathway,
      but still maintain activation of Stat5. The Bcr-Abl kinase inhibitor imatinib
      mesylate (1 microM) and two Jak2 kinase inhibitors strongly inhibited agar colony
      formation and the activation of Gab2 caused by Jak2. All of these findings
      indicate that Bcr-Abl oncoprotein requires the IL-3 receptor/Jak2/Stat5 pathways
      for oncogenic transformation of NIH 3T3 fibroblasts.

PMID- 18071310
TI  - Hsp90-inhibitor geldanamycin abrogates G2 arrest in p53-negative leukemia cell
      lines through the depletion of Chk1.
AB  - Checkpoint protein Chk1 has been identified as an Hsp90 client. Treatment with
      100 nM geldanamycin (GM) for 24 h markedly reduced the Chk1 amount in Jurkat and
      ML-1 leukemia cell lines. Because Chk1 plays a central role in G2 checkpoint, we
      added GM to G2-arrested Jurkat and HL-60 cells pretreated with 50 nM doxorubicin
      for 24 h. GM slowly released both cell lines from doxorubicin-induced G2 arrest
      into G1 phase. GM also abrogated ICRF-193-induced decatenation G2 checkpoint in
      Jurkat and HL-60 cells. Western blot analysis showed that addition of GM
      attenuates doxorubicin- and ICRF-193-induced Chk1 phosphorylation at Ser345. GM,
      however, failed to abrogate G2 arrest in p53-positive ML-1 cells maybe due to the
      p21 induction. GM released HeLa cells from doxorubicin-induced G2 arrest but
      trapped them at M phase. Flow cytometric analysis showed that addition of GM
      converted doxorubicin-induced necrosis into apoptosis in Jurkat cells. Colony
      assay indicated that although GM has a weak cytotoxic effect as a single agent,
      it dramatically intensifies the cytotoxicity of doxorubicin and ICRF-193 in
      Jurkat and HL-60 cells. These results suggest that abrogation of G2 checkpoint by
      GM may play a central role in sensitizing p53-negative tumor cells to DNA
      damaging and decatenation-inhibiting agents.

PMID- 18071311
TI  - Oncolytic adenoviral mutants induce a novel mode of programmed cell death in
      ovarian cancer.
AB  - Oncolytic adenoviral mutants have considerable activity in ovarian cancer.
      However, the mechanisms by which they induce cell death remain uncertain. dl922
      947, which contains a 24 bp deletion in E1A CR2, is more potent than both E1A
      wild-type adenoviruses and the E1B-55K deletion mutant dl1520 (Onyx-015). We
      investigated the mode of death induced by three E1A CR2-deleted replicating
      adenoviruses in models of ovarian cancer and also the importance of E3 11.6
      (adenovirus death protein) in determining this mode of death. Ovarian cancer
      cells were infected with dl922-947 (E3 11.6+) and dlCR2 (E3 11.6-). We also
      generated dlCR2 tSmac, which also encodes the gene for processed Smac/DIABLO.
      Classical apoptosis does not occur in adenoviral cell death and there is no role
      for mitochondria. Expression of Smac/DIABLO does not enhance cytotoxicity nor
      increase apoptotic features. A role for cathepsins and lysosomal membrane
      permeability was excluded. Autophagy is induced, but is not the mode of death and
      may act as a cell survival mechanism. There is no evidence of pure necrosis,
      while the presence of E3 11.6 does not modulate the mode or extent of cell death.
      Thus, E1A CR2-deleted oncolytic adenoviral cytotoxicity in ovarian cancer may
      define a novel mode of programmed cell death.

PMID- 18071312
TI  - Combinatorial action of the HDAC inhibitor trichostatin A and etoposide induces
      caspase-mediated AIF-dependent apoptotic cell death in non-small cell lung
      carcinoma cells.
AB  - Commonly used regimens in cancer therapy rely on the induction of apoptotic cell
      death, and drug resistance can be attributed, at least in part, to a disabled
      apoptotic program. Non-small cell lung carcinomas (NSCLC), exhibit an intrinsic
      resistance to chemotherapy. Here, we show that co-treatment with etoposide (VP16)
      and the pan-histone deacetylase (HDAC) inhibitor trichostatin A (TSA), but not
      valproic acid (VPA), induced apoptotic cell death in drug-resistant NSCLC cells.
      Co-treatment, but not single treatment, with VP16 and TSA induced apoptosis in a
      caspase-dependent manner accompanied by a crucial decrease in Bcl-xL expression
      allowing Bax activation and subsequent initiation of the apoptosis inducing
      factor (AIF)-dependent death pathway. Importantly, AIF proved to be required for
      the effects of TSA/VP16 as RNA knockdown of AIF resulted in a complete
      abolishment of TSA/VP16-induced apoptotic cell death in drug-resistant NSCLC
      cells. Our results thus provide evidence for the requirement of both caspase
      dependent and caspase-independent apoptotic pathways in TSA/VP16-mediated death
      of drug-resistant NSCLC cells, and extend previous suggestions that HDAC
      inhibitors in combination with conventional chemotherapeutic drugs could be
      valuable in the treatment of NSCLC cancer and other malignancies in which Bcl-xL
      is overexpressed.

PMID- 18071313
TI  - Distinct genomic aberration patterns are found in familial breast cancer
      associated with different immunohistochemical subtypes.
AB  - Five breast cancer subtypes have been described in sporadic breast cancer (SBC)
      using expression arrays: basal-like, ERBB2, normal breast-like, luminal A and B.
      These molecular subtypes show different genomic aberration patterns (GAPs).
      Recently, our group described these breast cancer subtypes in 50 non-BRCA1/2
      familial tumors using immunohistochemistry assays. We extended this study to the
      other classes of familial breast cancer (FBC), including 62 tumors (18 BRCA1, 16
      BRCA2 and 28 non-BRCA1/2), with the same panel of 25 immunohistochemical (IHC)
      markers and histological grade obtaining a similar classification. We combined
      these data with results generated by a 1 Mb BAC array-based CGH study to evaluate
      the genomic aberrations of each group. We found that BRCA1-related tumors are
      preferentially basal-like, whereas non-BRCA1/2 familial tumors are mainly luminal
      A subtype. We described distinct GAPs related to each IHC subtype. Basal tumors
      had a greater number of gains/losses, while luminal B tumors had more high-level
      DNA amplifications. Our data are similar to those obtained in SBC studies,
      highlighting the existence of distinct genetic pathways of tumor evolution,
      common to both SBC and FBC.

PMID- 18071314
TI  - Loss of cyclin D1 in concert with deregulated estrogen receptor alpha expression
      induces DNA damage response activation and interrupts mammary gland
      morphogenesis.
AB  - We have previously shown that increased and deregulated estrogen receptor alpha
      expression in the mammary gland leads to the development of proliferative disease
      and cancer. To address the importance of cyclin D1 in ERalpha-mediated mammary
      tumorigenesis, we crossed ERalpha-overexpressing mice with cyclin D1 knockout
      mice. Mammary gland morphogenesis was completely interrupted in the ERalpha
      overexpressing cyclin D1-deficient triple transgenic mice. In addition to a
      highly significant reduction in mammary epithelial cell proliferation, cyclin E
      was upregulated resulting in DNA damage checkpoint activation and apoptosis. This
      imbalance between proliferative and apoptotic rates in conjunction with
      remarkable structural defects and cellular disorganization in the terminal end
      buds interrupted ductal morphogenesis. Interestingly, the structure of the
      mammary fat pad was fundamentally altered by the consequences of overexpressing
      ERalpha in the epithelial cells in the absence of cyclin D1 illustrating how
      alterations in the epithelial compartment can impact surrounding stromal
      composition. Transplantation of embryonic ERalpha-overexpressing and cyclin D1
      deficient mammary epithelium into the cleared fat pad of wild-type mice did not
      rescue the aberrant mammary gland phenotype indicating that it was intrinsic to
      the mammary epithelial cells. In conclusion, although cyclin D1 is not essential
      for proliferation of normal mammary epithelial cells, ERalpha-overexpressing
      cells are absolutely dependent on cyclin D1 for proliferation. This differential
      requirement for cyclin D1 in normal vs abnormal mammary epithelial cells supports
      the application of cyclin D1 inhibitors as therapeutic interventions in ERalpha
      overexpressing breast cancers.

PMID- 18071315
TI  - B-Raf(V600E) signaling deregulates the mitotic spindle checkpoint through
      stabilizing Mps1 levels in melanoma cells.
AB  - The B-Raf(V600E) mutant, found in 65% of human melanomas, drives constitutive
      activation of the extracellular signal-regulated kinase (ERK) pathway and is
      implicated in tumorigenesis. Recently, we showed that B-Raf is important for
      spindle formation and the mitotic spindle checkpoint arrest. In this study, we
      demonstrate that B-Raf(V600E) signaling deregulates the spindle checkpoint as a
      consequence of stabilizing monopolar spindle 1 (Mps1) levels in human melanoma
      cells. Upon introducing the B-Raf(V600E) mutant into wild-type B-Raf melanoma
      cells, Mps1 protein and activity increased 3- and 10-fold, respectively. In
      addition, Mps1 became hyperphosphorylated, which correlated with stabilization of
      Mps1 protein levels. In contrast, reduction of B-Raf by RNAi or inactivation of
      ERK by the MEK inhibitor U0126 resulted in a precipitous decline in Mps1 levels.
      Together, these results suggest that B-Raf signaling through ERK regulates the
      stability of Mps1. Finally, B-Raf(V600E) expression induces a mitotic delay due
      to promoting robust activation of the mitotic spindle checkpoint. These effects
      were dependent on the induction of Mps1 levels by oncogenic B-Raf(V600E) as shown
      by depleting Mps1 with short interfering RNA. Collectively, our findings
      implicate a new mechanism through which B-Raf(V600E) exerts its oncogenic effects
      in melanoma.

PMID- 18071316
TI  - Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via
      ubiquitin-mediated degradation at the G1-S transition.
AB  - The tumor suppressor RASSF1A is inactivated in many human cancers and is
      implicated in regulation of microtubule stability, cell cycle progression and
      apoptosis. However, the precise mechanisms of RASSF1A action and their regulation
      remain unclear. Here we show that Skp2, an oncogenic subunit of the Skp1-Cul1-F
      box ubiquitin ligase complex, interacts with, ubiquitinates, and promotes the
      degradation of RASSF1A at the G1-S transition of the cell cycle. This Skp2
      dependent destruction of RASSF1A requires phosphorylation of the latter on serine
      203 by cyclin D-cyclin-dependent kinase 4. Interestingly, mutation of RASSF1A
      phosphorylation site Ser(203) to alanine results in a delay in cell cycle
      progression from G1 to S phase. Moreover, enforced expression of Skp2 abolishes
      the inhibitory effect of RASSF1A on cell proliferation. Finally, the delay in G1
      S progression after Skp2 removal is normalized by depletion of RASSF1A. These
      findings suggest that the Skp2-mediated degradation of RASSF1A plays an important
      role in cell proliferation and survival.

PMID- 18071317
TI  - Aberrant nucleocytoplasmic localization of the retinoblastoma tumor suppressor
      protein in human cancer correlates with moderate/poor tumor differentiation.
AB  - Inactivation of the retinoblastoma (RB) tumor suppressor pathway, via elevated
      cyclin-dependent kinase (CDK) activity, is observed in majority of human cancers.
      Since CDK deregulation is evident in most cancer cells, pharmacological CDK
      inhibition has become an attractive therapeutic strategy in oncology. We recently
      showed that an oncogenic CDK4(R24C) mutation alters the subcellular localization
      of the normally nuclear RB phosphoprotein. Here, using 71 human cancer cell lines
      and over 300 primary human cancer tissues, we investigated whether changes in RB
      subcellular localization occur during human cancer progression. We uncover that
      diverse human cancers and their derived cell lines, particularly those with poor
      tumor differentiation, display significant cytoplasmic mislocalization of
      ordinarily nuclear RB. The nucleocytoplasmically distributed RB was derived via
      CDK-dependent and Exportin1-mediated nuclear export. Indeed, cytoplasmically
      mislocalized RB could be efficiently confined to the nucleus by pharmacologically
      reducing CDK activity or by inhibiting the Exportin1-mediated nuclear export
      pathway. Our observations uncover a post-translational CDK-dependent mechanism of
      RB inactivation and suggest that cytoplasmically localized RB may harbor a tumor
      promoting function. We propose that RB inactivation, via aberrant
      nucleocytoplasmic transport, may disrupt normal cell differentiation programs and
      accelerate the cancer process. These results are evidence that tumor cells
      modulate the protein transport machinery thereby making the protein transport
      process a viable therapeutic target.

PMID- 18071318
TI  - In neuroblastic tumours, Schwann cells do not harbour the genetic alterations of
      neuroblasts but may nevertheless share the same clonal origin.
AB  - Neuroblastic tumours are composed of variable proportions of neuroblasts and
      Schwann cells. Whether both components share a common neoplastic origin is highly
      debated and discrepant results have been reported about the presence of tumour
      related genetic alterations in Schwann cells. We have used X-methylation analysis
      and array-CGH to investigate contiguous Schwannian and neuroblastic areas in
      tumours with a nodular pattern. A skewed X inactivation was observed in four out
      of five stromal components. Interestingly, in these four cases, the X
      inactivation profiles of the neuroblastic components were identical to the
      matched stromal areas. However, whereas all neuroblastic areas displayed
      chromosomal imbalances, no alteration was found in any Schwann cell components.
      Similarly, no alteration was observed in a series of 19 tumours with a single
      stroma-rich component, which occasionally exhibited a skewed X-inactivation
      pattern (3/17 informative tumours). Altogether, this indicates that most stroma
      rich tumours display a polyclonal proliferation and that Schwann cells do not
      derive from neuroblasts. However, in tumours with both stroma-rich and -poor
      components, our results suggest that cells from both areas share a common
      progenitor.

PMID- 18071319
TI  - Aberrant expression of extracellular signal-regulated kinase 5 in human prostate
      cancer.
AB  - Abnormal intracellular signaling contributes to carcinogenesis and may represent
      novel therapeutic targets. mitogen/extracellular signal-regulated kinase kinase-5
      (MEK5) overexpression is associated with aggressive prostate cancer. In this
      study, we examined the role of extracellular signal-regulated kinase (ERK5, an
      MAPK and specific substrate for MEK5) in prostate cancer. ERK5 immunoreactivity
      was significantly upregulated in high-grade prostate cancer when compared to
      benign prostatic hyperplasia (P<0.0001). Increased ERK5 cytoplasmic signals
      correlated closely with Gleason sum score (P<0.0001), bony metastases (P=0.0044)
      and locally advanced disease at diagnosis (P=0.0023), with a weak association
      with shorter disease-specific survival (P=0.036). A subgroup of patients showed
      strong nuclear ERK5 localization, which correlated with poor disease-specific
      survival and, on multivariant analysis, was an independent prognostic factor
      (P<0.0001). Analysis of ERK5 expression in matched tumor pairs (before and after
      hormone relapse, n=26) revealed ERK5 nuclear expression was significantly
      associated with hormone-insensitive disease (P=0.0078). Similarly, ERK5 protein
      expression was increased in an androgen-independent LNCaP subline. We obtained
      the following in vitro and in vivo evidence to support the above expression data:
      (1) cotransfection of ERK5wt and MEK5D constructs in PC3 cells results in
      predominant ERK5 nuclear localization, similar to that observed in aggressive
      clinical disease; (2) ERK5-overexpressing PC3 cells have enhanced proliferative,
      migrative and invasive capabilities in vitro (P<0.0001), and were dramatically
      more efficient in forming tumors, with a shorter mean time for tumors to reach a
      critical volume of 1000 mm(3), in vivo (P<0.0001); (3) the MEK1 inhibitor,
      PD184352, blocking ERK1/2 activation at low dose, did not suppress proliferation
      but did significantly decrease proliferation at a higher dose required to inhibit
      ERK5 activation. Taken together, our results establish the potential importance
      of ERK5 in aggressive prostate cancer.

PMID- 18071320
TI  - Decisive role of cyclooxygenase-2 and lipocalin-type prostaglandin D synthase in
      chemotherapeutics-induced apoptosis of human cervical carcinoma cells.
AB  - The role of cyclooxygenase-2 (COX-2) in cancer remains controversial. Using
      cervical carcinoma cells (HeLa), the present study investigates the involvement
      of COX-2 in apoptosis elicited by the chemotherapeutics paclitaxel, cisplatin and
      5-fluorouracil. Each compound led to a profound induction of COX-2 expression and
      prostaglandin (PG) synthesis, accompanied by a substantial decrease of viability
      and enhanced apoptosis. Cells were significantly less sensitive to apoptotic
      death when either COX-2 expression or its activity was suppressed by small
      interfering RNA (siRNA) and by the selective COX-2 inhibitor NS-398,
      respectively. Experiments performed to clarify how COX-2 leads to apoptosis
      revealed a profound proapoptotic action of PGD2 and its dehydration product, 15
      deoxy-Delta(12,14) PGJ2 (15d-PGJ2). In line with these findings,
      chemotherapeutics-induced apoptosis was prevented by siRNA targeting lipocalin
      type PGD synthase (L-PGDS), which catalyses the isomerization of PGH(2) to PGD2.
      Moreover, apoptosis by chemotherapeutics, PGD2 and 15d-PGJ2 was suppressed by the
      peroxisome proliferator-activated receptor gamma (PPARgamma) antagonist, GW-9662
      or PPARgamma siRNA. Finally, a COX-2-dependent apoptotic mechanism of all
      investigated chemotherapeutics was confirmed in human lung cancer cells (A549) as
      well as in another cervical carcinoma cell line (C33A). Collectively, this study
      suggests COX-2 induction and synthesis of L-PGDS-derived, PPARgamma-activating
      PGs as a decisive target by which several chemotherapeutics induce apoptosis. COX
      2 is therefore suspected to sensitize cancer cells to apoptotic death under
      certain circumstances, suggesting that COX-2 inhibition during cancer therapy
      could diminish its efficacy.

PMID- 18071321
TI  - The multifaceted role of Notch in cardiac development and disease.
AB  - Notch receptors and their cognate ligands transduce crucial signals between cells
      in various tissues, and have been conserved across millions of years of
      evolution. Mutations in Notch signalling components result in congenital heart
      defects in humans and mice, demonstrating an essential role for Notch in
      cardiovascular development. The results of recent experiments implicate this
      signalling pathway in many stages of heart development, and provide mechanistic
      insight into the vital functions of Notch in the aetiology of several common
      forms of paediatric and adult cardiac disease.

PMID- 18071322
TI  - Coupling and coordination in gene expression processes: a systems biology view.
AB  - Genome-scale analyses have allowed us to progress beyond studying gene expression
      at the level of individual components of a given process by providing global
      information about functional connections between genes, mRNAs and their
      regulatory proteins. Such analyses have greatly increased our understanding of
      the interplay between different events in gene regulation and have highlighted
      previously unappreciated functional connections, including coupling between
      nuclear and cytoplasmic processes. Genome-wide approaches have also revealed
      extensive coordination within regulatory levels, such as the organization of
      transcription factors into regulatory motifs. Overall, these studies enhance our
      understanding of how the many components of the eukaryotic cell function as a
      system to allow both coordination and versatility in gene expression.

PMID- 18071330
TI  - The role of Gadd45a in the survival of melanocytes and melanoma cells.

PMID- 18071331
TI  - Sounding the alarm: multiple functions of host defense peptides.
AB  - The capacity of the skin and other organs to resist infection depends on the
      innate production of molecules known as antimicrobial peptides. Emerging evidence
      suggests that some of these peptides are important to immune defense by acting
      not only as natural antibiotics but also as cell-signaling molecules. In this
      issue Carretero et al. (2007) expand on these findings by demonstrating that
      expression of human cathelicidin alters multiple signaling pathways in a
      keratinocyte cell line and enhances wound re-epithelialization in ob/ob mice.

PMID- 18071332
TI  - Therapeutic interference: a step closer for pachyonychia congenita?
AB  - The identification of mutations in keratin genes as the cause of several
      inherited skin disorders raised the possibility that molecular-based therapies
      might be developed to treat these conditions. In this issue, Smith et al. (2007)
      have identified small interfering RNAs that specifically and potently silence
      keratin 6a expression. These molecules have great promise as therapeutic agents
      for the treatment of pachyonychia congenita.

PMID- 18071333
TI  - Titers of HIV-based vectors encoding shRNAs are reduced by a dicer-dependent
      mechanism.
AB  - Gene transfer vectors encoding short hairpin RNAs (shRNAs) are useful in
      deciphering gene function, and are being considered for therapeutic knockdown of
      target genes in humans. We constructed HIV-based vectors encoding shRNA against
      HIV coreceptor chemokine (C-C motif) receptor 5 (CCR5). Initially we noted that
      vectors encoding CCR5 shRNA showed >30-fold lower viral titers than those of the
      empty vector. Co-transfection of expression plasmids encoding CCR5 in the
      producer cells yielded a tenfold increase in viral titer, thereby indicating that
      CCR5 mRNA, rather than HIV vector mRNA, could be the target of CCR5 shRNA.
      Similar increases in vector titer were observed after the H1 promoter was
      deleted. When Nodamura-virus B2 protein or Adenovirus VA.1 RNA (inhibitors of the
      Dicer-dependent siRNA pathway) were added to the producer cells, the vector titer
      rose almost to the level of that of the empty vector. Near identical increases in
      titer were observed with siRNA specifically directed against Dicer. Quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) suggested that the
      effects were in part caused by reduction in vector RNA in the producer cells.
      Similar results were observed with a retroviral vector. These results suggest
      that retrovirally-encoded shRNAs reduce vector titer in the producer cells
      through a Dicer-dependent mechanism which, to a large extent, can be reversed by
      inhibiting that pathway. This may have important implications for large-scale
      production of RNA vectors encoding shRNAs.

PMID- 18071334
TI  - Overcoming immune tolerance against multiple myeloma with lentiviral calnexin
      engineered dendritic cells.
AB  - The key to successful cancer immunotherapy is to induce an effective anticancer
      immunity that will overcome the acquired cancer-specific immune tolerance. In
      this study, we found that dendritic cells (DCs) from multiple myeloma (MM)
      patients suppressed rather than induced a cancer cell-specific immune response.
      We demonstrated that CD4(+)CD25(high) T cells from MM patients suppressed the
      proliferation of activated peripheral blood lymphocytes. Further analysis
      illustrated that MM cell lysates or MM-specific idiotype immunoglobulins (MM Id
      Ig) specifically induced the expansion of peripheral CD4(+)CD25(high)FoxP3(high)
      T regulatory (Treg) cells in vitro. Supraphysiological expression of calnexin
      (CNX) using lentiviral (LV) vectors in DCs of MM patients overcame the immune
      suppression and enhanced MM-specific CD4 and CD8 T-cell responses. However,
      overexpression of CNX did not affect the peripheral expansion of Treg cells
      stimulated by MM antigens. Thus, the immune suppression effect of Treg cells in
      cancer patients may be overcome by improving antigen processing in DCs, which in
      turn may lower the activation threshold of the immune effector cells. This
      concept of modulating anticancer immunity by genetically engineering cancer
      patients' DCs may improve immunotherapeutic regimens in cancer treatment.

PMID- 18071335
TI  - Transcriptional activities of the Sleeping Beauty transposon and shielding its
      genetic cargo with insulators.
AB  - The Sleeping Beauty (SB) transposable element shows efficient transposition in
      human cells, and provides long-term transgene expression in preclinical animal
      models. Random chromosomal insertion of SB vectors represents a safety issue in
      human gene therapeutic applications, due to potential genotoxic effects
      associated with transposon integration. We investigated the transcriptional
      activities of SB in order to assess its potential to alter host gene expression
      upon integration. The untranslated regions (UTRs) of the transposon direct
      convergent, inward-directed transcription. Transcription from the 5'-UTR of SB is
      upregulated by the host-encoded factor high-mobility group 2-like 1 (HMG2L1), and
      requires a 65-base pair (bp) region not present in commonly used SB vectors. The
      SB transposase antagonizes the effect of HMG2L1, suggesting that natural
      transposase expression is under a negative feedback regulation. SB transposon
      vectors lacking the 65-bp region associated with HMG2L1-dependent upregulation
      exhibit benign transcriptional activities, at a level up to 100-times lower than
      that of the murine leukemia virus (MLV) long terminal repeat (LTR). Incorporation
      of chicken beta-globin HS4 insulator sequences in SB-based vectors reduces the
      transactivation of model promoters by transposon-borne enhancers, and thus may
      lower the risk of transcriptional activation of host genes situated close to a
      transposon insertion site.

PMID- 18071336
TI  - Virotherapy of ovarian cancer with polymer-cloaked adenovirus retargeted to the
      epidermal growth factor receptor.
AB  - Adenovirus gene therapy for intraperitoneal (IP) cancer is limited in clinical
      trials by inefficient tumor cell transduction and development of peritoneal
      adhesions. We have shown previously that normal virus tropism can be ablated by
      physically shielding the virus surface with reactive hydrophilic polymers and
      that linkage of novel ligands enables virus "retargeting" through chosen
      receptors. To achieve tumor-selective infection, polymer-coated virus was
      retargeted using murine epidermal growth factor (mEGF). The resulting mEGF
      polymer coated adenovirus lost its normal broad tropism and transduced cells
      selectively via the EGF receptor (EGFR). We assessed whether this approach could
      be used to target lytic "virotherapy" using wild-type adenovirus (Ad5WT) in a
      peritoneal xenograft model of human ovarian cancer. Oncolytic activity of Ad5WT
      was retained following polymer coating and mEGF-retargeting. Importantly,
      adhesion formation was markedly decreased compared with the unmodified virus, and
      no dose-limiting toxicities were observed following treatment with mEGF
      retargeted polymer-coated virus. Restricting virus tropism by physical coating,
      coupled with tumor-selective retargeting promises to combine good anticancer
      efficacy with acceptable toxicity, enabling application of elevated virus doses
      leading to an improved therapeutic outcome.

PMID- 18071338
TI  - Current status of gene therapy in Asia.
AB  - Asian countries, in particular China, Japan, and Korea, have been aggressively
      researching and developing gene medicines over the last 15 years or so. In China,
      an adenovirus expressing p53 was approved for commercial use in the year 2003,
      and has been on the actual market since then, becoming the world's first
      commercial gene-based drug. In Japan and Korea, many interesting scientific
      discoveries have been made, and industrially valuable technologies have been
      developed. It is particularly noteworthy to see that in these countries, gene
      therapy has been very keenly nurtured in relation with industrial and financial
      sectors. Despite remarkable progresses made in Asia, however, their activities
      have not been visibly noticed by many scientists in the US and European
      countries. This article briefly reviews key features of the past achievements and
      recent progresses made in three Asian countries.

PMID- 18071337
TI  - Exponential enhancement of oncolytic vesicular stomatitis virus potency by vector
      mediated suppression of inflammatory responses in vivo.
AB  - Oncolytic virotherapy is a promising strategy for treatment of malignancy,
      although its effectiveness is hampered by host antiviral inflammatory responses.
      The efficacy of treatment of oncolytic vesicular stomatitis virus (VSV) in rats
      bearing multifocal hepatocellular carcinoma (HCC) can be substantially elevated
      by antibody-mediated depletion of natural killer (NK) cells. In order to test the
      hypothesis that the oncotyic potency of VSV can be exponentially elevated by
      evasion of inflammatory responses in vivo, we constructed a recombinant VSV
      vector expressing equine herpes virus-1 glycoprotein G, which is a broad-spectrum
      viral chemokine binding protein (rVSV-gG). Infusion of rVSV-gG via the hepatic
      artery into immune-competent rats bearing syngeneic and multifocal HCC in their
      livers, resulted in a reduction of NK and NKT cells in the tumors and a 1-log
      enhancement in intratumoral virus titer in comparison with a reference rVSV
      vector. The treatment led to increased tumor necrosis and substantially prolonged
      animal survival without toxicities. These results indicate that rVSV-gG has the
      potential to be developed as an effective and safe oncolytic agent to treat
      patients with advanced HCC. Furthermore, the novel concept that oncolytic potency
      can be substantially enhanced by vector-mediated suppression of host antiviral
      inflammatory responses could have general applicability in the field of oncolytic
      virotherapy for cancer.

PMID- 18071339
TI  - Weighing the data in studies of the glycaemic index.

PMID- 18071340
TI  - Association between polymorphisms in the Clock gene, obesity and the metabolic
      syndrome in man.
AB  - OBJECTIVE: Accumulating evidence raises the hypothesis that dysregulation of
      intrinsic clock mechanisms are involved in the development of the metabolic
      syndrome, type 2 diabetes mellitus and cardiovascular disease. The aim of the
      present study was to investigate the relationship between three known common
      polymorphisms in the Clock gene and features of the metabolic syndrome in man.
      METHODS: Genotype and haplotype analysis was carried out in a cohort of 537
      individuals from 89 families characterized for inflammatory, atherothrombotic and
      metabolic risk associated with insulin resistance. RESULTS: Heritability of the
      metabolic syndrome, defined according to International Diabetes Federation
      criteria, was 0.40. Haplotype analysis indicated three common haplotypes: CAT,
      TGT and CGC (rs4864548-rs3736544-rs1801260) with frequencies of 31, 33 and 28%,
      respectively. The CGC haplotype was less prevalent in subjects with the metabolic
      syndrome (P=0.0015) and was associated with lower waist circumference (P=0.007),
      lower hip circumference (P=0.023), lower body mass index (P=0.043) and lower
      leptin levels (P=0.028). The CAT haplotype was significantly associated with the
      presence of the metabolic syndrome (P=0.020). CONCLUSIONS: These findings suggest
      that the Clock gene CGC haplotype may be protective for the development of
      obesity and support the hypothesis that genetic variation in the Clock gene may
      play a role in the development of the metabolic syndrome, type 2 diabetes and
      cardiovascular disease.

PMID- 18071341
TI  - Effect of hypocaloric diet plus sibutramine treatment on hormonal and metabolic
      features in overweight and obese women with polycystic ovary syndrome: a
      randomized, 24-week study.
AB  - OBJECTIVE: To examine the effect of hypocaloric diet plus sibutramine on body
      composition, hormonal and metabolic parameters in overweight and obese patients
      with polycystic ovary syndrome (PCOS). DESIGN: Open-label, randomized study at an
      outpatient clinic. PATIENTS: A total of 59 overweight and obese (18-39 years old)
      women with PCOS. MEASUREMENTS: All patients were placed in a hypocaloric diet
      plus sibutramine (10 mg per day) for the first month and then on a hypocaloric
      diet plus sibutramine (10 mg per day, group S) or hypocaloric diet only (group D)
      for the subsequent 6 months. Body composition, hormonal and metabolic features
      and insulin sensitivity (oral glucose tolerance test, OGTT) were evaluated at
      baseline and at 3 and 6 months of treatment. RESULTS: Body weight reduced in both
      groups but the reduction was greater with sibutramine (-15.4+/-1.1 vs -11.1+/
      1.9% in groups S and D, respectively, P<0.05). At 6 months, a greater percent of
      patients lost more than 10% of initial body weight in group S than D (81 vs
      52.9%). In both groups, all women with abnormal OGTT at baseline presented normal
      glucose tolerance after 6 months. Free androgen index (FAI), glucose area under
      the curve and fasting triglyceride (TG) concentration were reduced after 6 months
      in group S only (P<0.05). No changes in cardiovascular risk factors, prolactin
      and hepatic enzymes levels were observed in both groups. CONCLUSION: A
      hypocaloric diet and a diet plus sibutramine both result in significant weight
      loss in overweight and obese women with PCOS. Patients who received sibutramine
      showed a greater weight loss and improvement in hyperandrogenemia and insulin
      sensitivity after 6 months of treatment. The amelioration of insulin resistance
      in this group could not be totally explained by weight loss. Total testosterone,
      FAI and TG levels reduction could be a possible mechanism. Finally, sibutramine
      increased compliance to diet and it was well tolerated from these patients.

PMID- 18071342
TI  - The effect of viscosity on ad libitum food intake.
AB  - BACKGROUND: Energy-yielding liquids elicit weak suppressive appetite responses
      and weak compensatory responses, suggesting that liquid calories might lead to a
      positive energy balance. However, data is often derived from foods differing in
      many characteristics other than viscosity. OBJECTIVE: To investigate the effect
      of viscosity on ad libitum food intake in real-life setting and to investigate
      whether a difference in ad libitum intake is related to eating rate and/or eating
      effort. DESIGN: In real-life setting 108 nonrestrained subjects (26+/-7 years,
      BMI 22.7+/-2.4 kg m(-2)) received a chocolate flavored liquid, semi-liquid and
      semi-solid milk-based product, similar in palatability, macronutrient composition
      and energy density. In laboratory setting 49 nonrestrained subjects (24+/-6
      years, BMI 22.2+/-2.3 kg m(-2)) received the liquid or semi-solid product. Effort
      and eating rate were controlled by means of a peristaltic pump. RESULTS: In real
      life setting the intake of the liquid (809+/-396 g) was respectively 14 and 30%
      higher compared to the semi-liquid (699+/-391 g) and semi-solid product (566+/
      311 g; P<0.0001). In laboratory setting, removing eating effort, resulted in a
      29% (P<0.0001) intake difference between liquid (319+/-176 g) and semi-solid
      (226+/-122 g). Standardizing eating rate resulted in 12% difference between
      liquid (200+/-106 g) and semi-solid (176+/-88 g; P=0.24). If not controlled, the
      difference in intake between liquid (419+/-216 g) and semi-solid (277+/-130 g)
      was comparable to the real-life setting (34%; P<0.0001). CONCLUSIONS: Products
      different in viscosity but similar in palatability, macronutrient composition and
      energy density lead to significant differences in intake. This difference is
      partially explained by the higher eating rate of liquids.

PMID- 18071343
TI  - Promoter adiponectin polymorphisms and waist/hip ratio variation in a prospective
      French adults study.
AB  - BACKGROUND: Adiponectin expression and plasma concentrations are decreased in
      human and animal models of obesity. Several single nucleotide polymorphisms
      (SNPs) in the adiponectin gene are known to influence the plasmatic concentration
      of the encoded protein. Some of these adiponectin polymorphisms have been
      associated with BMI in cross-sectional studies. OBJECTIVE: The aim of our study
      was to examine the longitudinal relationships between adiponectin gene
      polymorphisms and anthropometric indices. DESIGN: Two adiponectin gene (ADIPOQ)
      SNPs, -11391G>A and -11377C>G, were genotyped in 837 French Caucasian subjects
      from the SUpplementation en VItamines et Mineraux Anti-oXydants (SU.VI.MAX)
      cohort. Anthropometric scores were measured at three clinical examinations over a
      7-year period. RESULTS: For -11391G>A as well as for -11377C>G, we detected no
      association between the variant allele and anthropometric measurements at
      baseline. Considering longitudinal effects, we detected moderately higher waist
      to-hip ratio (WHR) changes for the carriers of the -11391A (P=0.02) and -11377C
      (P=0.03) allele over the follow-up of the study. -11391G>A and -11377C>G define
      haplotypes associated also with WHR measurements and their changes over the
      follow-up of the study. Diploid configurations that combine -11391A and -11377C
      were associated with significantly higher WHR changes (DeltaCE: P=0.02) compared
      to other haplotypes. In addition, higher adiponectin levels were observed in
      AC/AC diplotypes compared to GG/GG carriers (P<0.0001). CONCLUSION: In the
      SU.VI.MAX study, genetic variations in the adiponectin gene affect abdominal fat
      gain over life span.

PMID- 18071344
TI  - Healthy habits: efficacy of simple advice on weight control based on a habit
      formation model.
AB  - OBJECTIVE: To evaluate the efficacy of a simple weight loss intervention, based
      on principles of habit formation. DESIGN: An exploratory trial in which
      overweight and obese adults were randomized either to a habit-based intervention
      condition (with two subgroups given weekly vs monthly weighing; n=33, n=36) or to
      a waiting-list control condition (n=35) over 8 weeks. Intervention participants
      were followed up for 8 months. PARTICIPANTS: A total of 104 adults (35 men, 69
      women) with an average BMI of 30.9 kg m(-2). INTERVENTION: Intervention
      participants were given a leaflet containing advice on habit formation and simple
      recommendations for eating and activity behaviours promoting negative energy
      balance, together with a self-monitoring checklist. MAIN OUTCOME MEASURES: Weight
      change over 8 weeks in the intervention condition compared with the control
      condition and weight loss maintenance over 32 weeks in the intervention
      condition. RESULTS: At 8 weeks, people in the intervention condition had lost
      significantly more weight (mean=2.0 kg) than those in the control condition (0.4
      kg), with no difference between weekly and monthly weighing subgroups. At 32
      weeks, those who remained in the study had lost an average of 3.8 kg, with 54%
      losing 5% or more of their body weight. An intention-to-treat analysis (based on
      last-observation-carried-forward) reduced this to 2.6 kg, with 26% achieving a 5%
      weight loss. CONCLUSIONS: This easily disseminable, low-cost, simple intervention
      produced clinically significant weight loss. In limited resource settings it has
      potential as a tool for obesity management.

PMID- 18071345
TI  - A new variation in the promoter region, the -604 C>T, and the Leu72Met
      polymorphism of the ghrelin gene are associated with protection to insulin
      resistance.
AB  - OBJECTIVE: Previous studies suggested that polymorphisms in the coding region of
      the preproghrelin were involved in the etiology of obesity and might modulate
      glucose-induced insulin secretion. We evaluated the association of a new
      variation, -604C>T, in the promoter region of the ghrelin gene, of Leu72Met
      (247C>A) and of Gln90Leu (265A>T), all haplotype-tagging single nucleotide
      polymorphisms (SNPs), with measures of insulin sensitivity in 1420 adult
      individuals. RESEARCH METHODS: The three SNPs were genotyped using ABI PRISM 7900
      HT Sequence Detection System. We used multiple linear regression analysis for
      quantitative traits and THESIAS software for haplotype analysis. RESULTS: We
      observed a protective effect exerted by Met72 variant of Leu72Met SNP on insulin
      resistance parameters; a significant decreasing trend from Leu/Leu to Leu/Met and
      to Met/Met homozygous subjects in triglycerides, fasting insulin levels and HOMA
      IR index (P=0.02, 0.01 and 0.003, respectively), and, consistently, an increase
      in ghrelin levels (P=0.003) was found. A significant decrease from CC to TC and
      to TT genotypes in insulin levels and HOMA-IR index was also detected (P=0.00l
      for both), but only in subjects homozygous for Leu72, where the protective effect
      of Met72 was not present. The haplotype analysis results supported the data
      obtained by the evaluation of each single SNP, showing the highest value of
      insulin levels and HOMA-IR index in the -604(c)247(c) haplotype intermediate
      value in -604(T)247(C) and lowest value in -604(C)247(A). CONCLUSION: Our
      observations suggest a protective role of the Met72 variant and of -604 T allele
      in modulating insulin resistance. These SNPs or an unknown functional variant in
      linkage disequilibrium could increase ghrelin levels and probably insulin
      sensitivity.

PMID- 18071346
TI  - The NR4A family of orphan nuclear receptors are not required for adipogenesis.
AB  - Nuclear hormone receptors of the NR4A subfamily are rapidly induced during the
      early stages of adipogenesis, leading to the speculation that they may have
      important roles in this process. One of the three subfamily members, Nur77 has
      also been shown to play key roles in energy expenditure and lipolysis in skeletal
      muscle and in the control of hepatic gluconeogenesis. We, therefore, examined the
      role of NR4A factors in adipogenesis using the well-characterized 3T3-L1
      preadipocyte model. Inhibition of Nur77 expression using siRNA did not affect
      induction of adipogenic genes, nor the accumulation of lipid. To inhibit the
      activity of all the three NR4A family members, we generated preadipocytes stably
      expressing a well-characterized dominant-negative Nur77 (DN-Nur77), known to
      block the function of the other NR4A factors, Nurr1 and Nor1, as well as Nur77.
      While the increased NR4A activity observed following adipogenic induction was
      completely abolished in these cells, DN-Nur77 expression did not affect the
      expression of genes characteristic of terminally differentiated adipocytes and
      had no impact on lipid accumulation in these cells. Thus, while members of the
      NR4A subfamily of nuclear receptors may have important metabolic roles in
      skeletal muscle and liver, we demonstrate that they are dispensable for normal
      adipocyte development.

PMID- 18071347
TI  - Predictors of survival after hepatic resection among patients with colorectal
      liver metastasis.
AB  - Studies suggest improved survival following resection of colorectal cancer liver
      metastases (CLMs). We investigated predictors of survival among patients with CLM
      who underwent hepatic resection using the SEER-Medicare database to identify
      patients >/=65 years diagnosed with CLM, 1991-2003, who underwent hepatectomy.
      Cox proportional hazards models were used to identify factors associated with
      survival after hepatectomy. Of 923 patients with CLM who underwent hepatectomy,
      514 were stages I-III and developed CLM>6 months after diagnosis (metachronous),
      and 409 were stage IV with CLM at diagnosis (synchronous). From the date of
      hepatectomy, 5 year survival was 22%; younger age, being married, female gender,
      surgery in an NCI-designated cancer centre, fewer comorbidities, fewer positive
      lymph nodes, and lower grade were associated with improved survival. Both 5
      fluorouracil (5FU)-based chemotherapy and hepatic arterial infusion (HAI) of
      floxuridine-based chemotherapy following hepatectomy improved survival (HR=0.62,
      95% CI: 0.50-0.78; HR=0.51, 95% CI: 0.28-0.97, respectively) in the synchronous,
      but not metachronous, group. The HR for overall mortality was higher in hospitals
      with a high vs low procedure volume (0.75, 95% CI: 0.58-0.94). A substantial
      subgroup of patients with CLM who undergo hepatectomy experiences long-term
      survival. High hospital procedure volume and use of 5FU-based or HAI-based
      chemotherapy after resection were associated with improved prognosis.

PMID- 18071348
TI  - '1-8 interferon inducible gene family': putative colon carcinoma-associated
      antigens.
AB  - D(b-/-)xbeta2 microglobulin (beta2m) null mice transgenic for a chimeric HLA
      A2.1/D(b)-beta2m single chain (HHD mice) are an effective biological tool to
      evaluate the antitumour cytotoxic T-lymphocyte response of known major
      histocompatibility-restricted peptide tumour-associated antigens, and to screen
      for putative unknown novel peptides. We utilised HHD lymphocytes to identify
      immunodominant epitopes of colon carcinoma overexpressed genes. We screened with
      HHD-derived lymphocytes over 500 HLA-A2.1-restricted peptides derived from colon
      carcinoma overexpressed genes. This procedure culminated in the identification of
      seven immunogenic peptides, three of these were derived from the 'human 1-8D gene
      from interferon inducible gene' (1-8D). The 1-8D gene was shown to be
      overexpressed in fresh tumour samples. The three 1-8D peptides were both
      antigenic and immunogenic in the HHD mice. The peptides induce cytotoxic T
      lymphocytes that were able to kill a colon carcinoma cell line HCT/HHD, in vitro
      and retard its growth in vivo. One of the peptides shared by all the 1-8 gene
      family primed efficiently normal human cytotoxic T lymphocyte precursors. These
      results highlight the 1-8D gene and its homologues as putative immunodominant
      tumour-associated antigens of colon carcinoma.

PMID- 18071353
TI  - Complications and outcomes after spinal cord tumor resection in the United States
      from 1993 to 2002.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Data on patient outcomes
      after surgery for spinal cord tumors have been derived from single-institution
      series. The objective of this study is to report inpatient complications,
      mortality and outcomes on a national level. SETTING: United States, national
      inpatient care database. METHODS: The National Inpatient Sample (NIS) was used to
      identify 19,017 admissions for resection of a spinal cord tumor in the United
      States from 1993 to 2002. The effects of patient and hospital characteristics on
      inpatient outcomes were analyzed using logistic regression. RESULTS: The in
      hospital mortality rate and the complication rate were 0.55 and 17.5%,
      respectively. Urinary and renal complications (3.7%), postoperative hemorrhages
      or hematomas (2.5%) and pulmonary complications (2.4%) were the most common
      complications reported. A single postoperative complication increased the length
      of stay by 4 days, increased the mortality rate by sixfold and added over $10,000
      to hospital charges. Multivariate analysis showed that complications were more
      likely in African Americans and patients with multiple comorbidities. The odds of
      an adverse outcome increased significantly with age greater than 64, multiple
      comorbidities and postoperative complications. CONCLUSION: A national perspective
      on inpatient outcomes after resection of spinal cord tumors has been provided.
      The significant negative impact of postoperative complications on mortality and
      resource utilization has been demonstrated. We have identified advanced age and
      multiple comorbidities as risk factors that predict adverse outcome. Furthermore,
      this study highlights the importance of avoidance, recognition and prompt
      management of nonneurologic complications.

PMID- 18071354
TI  - Screening for depression and anxiety in spinal cord injury with DASS-21.
AB  - STUDY DESIGN: Comparison of two self-report instruments with a structured
      diagnostic interview. OBJECTIVE: To investigate the properties of the Depression
      Anxiety Stress Scales-21 (DASS-21) in patients with spinal cord injuries.
      SETTING: South Australian Spinal Cord Injuries Service, Hampstead Rehabilitation
      Centre, Northfield, South Australia. METHODS: Forty paraplegic or tetraplegic
      patients participated. Two self-report measures, DASS-21 and Brief Symptom
      Inventory (BSI), assessed Depression, Anxiety and Stress. These measures were
      compared with each other and with diagnoses based on the Mini International
      Neuropsychiatric Interview. RESULTS: Mean scores on both self-report measures
      were below clinical threshold levels. Prevalence rates of anxiety and depression
      were higher on DASS-21 than on BSI. DASS-21 was as sensitive as BSI, but had
      lower specificity to detect anxiety and depression. CONCLUSION: DASS-21 is a
      promising screening measure for patients with spinal cord injury in a
      rehabilitation setting. It has greater sensitivity for identifying those with
      possible anxiety disorders than it does for those with depressive disorders.

PMID- 18071355
TI  - Objective assessment of mobility of the spinal cord injured in a free-living
      environment.
AB  - STUDY DESIGN: An exploratory study of the practicality and feasibility of an
      instrument. OBJECTIVES: To adapt an activity monitor for use on a wheelchair to
      assess long-term mobility in a free-living environment in the spinal cord injury
      (SCI) population, and to explore the utility of the data collected. SETTING:
      Glasgow, UK. METHODS: An activity monitor was adapted for use on a wheelchair
      wheel. The monitor was used to assess, for 1 week, the wheelchair mobility of
      seven participants with SCI who only used a wheelchair. In conjunction with a
      second monitor on the thigh the mobility of seven participants with SCI who used
      a wheelchair and upright mobility, and five healthy non-wheelchair users, were
      assessed for 1 day. RESULTS: The adapted monitor collected 1260 h of data and was
      suitable for use on both manual and electric wheelchairs. During 1 week,
      participants with SCI who only used a wheelchair spent between 4 and 13 h moving
      in the wheelchair, covering a distance of between 7 and 28 km. Distinct
      differences in mobility were shown between participants with an SCI and non
      wheelchair users. The differences in time spent in mobility activities between
      the groups of participants with SCI were smaller. CONCLUSIONS: The system was
      successfully used in this group of participants with SCI, and could provide
      useful information on the mobility of people with SCI in a free-living
      environment.

PMID- 18071356
TI  - Incidence of non-traumatic spinal cord injury in Victoria, Australia: a
      population-based study and literature review.
AB  - STUDY DESIGN: Data extraction from a state-wide, population-based, health
      administration database of hospital admissions. OBJECTIVE: To determine the
      incidence of non-traumatic spinal cord injury (NTSCI). SETTING: Victoria,
      Australia. METHODS: All patients admitted to hospital with a new onset of NTSCI,
      or who developed NTSCI after hospitalization, between 1 July 2000 and 30 June
      2006, were identified using a population-based database. Age and gender of NTSCI
      patients were recorded. RESULTS: The number of adults aged 15 years and older
      with NTSCI in each of the 12-month periods was 82, 111, 96, 108, 133 and 101. The
      average age-adjusted incidence rate of NTSCI in adults was 26.3 cases per million
      per year. There was no statistically significant increase in the age-adjusted
      incidence of NTSCI over the study period (Spearman's rho=0.35, P=0.5). The
      incidence of NTSCI was significantly greater than the reported incidence for
      traumatic spinal cord injury (chi2 (1)=19.5, P<0.0000). There was a very strong
      correlation between age and the incidence of NTSCI, for both men (Spearman's
      rho=1, P<0.0000) and women (Spearman's rho=0.98, P=0.0000). Men had a
      statistically significantly (chi2 (1)=13.1, P=0.000) higher incidence of NTSCI
      (30.5 million adults per year) compared to women (22.9 million adults per year).
      The average incidence of NTSCI in children <15 years was 0.7 cases per million
      per year. CONCLUSION: NTSCI is strongly correlated with age and is more common
      than traumatic spinal cord injury. The method used in this study to calculate the
      incidence of NTSCI can be used to monitor the anticipated increase in the
      incidence of NTSCI in the years ahead, and can be used to in comparative studies.

PMID- 18071357
TI  - JH Frisbie Salt wasting, hypotension, polydipsia, and hyponatremia and the level
      of spinal cord injury.

PMID- 18071359
TI  - Self/non-self discrimination and the problem of keeping T cells alive.
AB  - Burnet appreciated the requirement for self/non-self discrimination and
      presciently postulated elimination of auto-aggressive cells during early life. He
      could not have known that, for T cells, a limited degree of autoreactivity is
      beneficial for the immune system. Here, we review evidence that recognition of
      self-components keeps T cells alive and regulates self-tolerance.

PMID- 18071360
TI  - Testicular cancer in twins: a meta-analysis.
AB  - In a meta-analysis of testicular cancer in twins, twins had a 30% increased risk
      (estimate 1.31, 95% CI 1.1-1.6), providing indirect support for the hypothesis
      that in utero hormone variations influence risk of testicular cancer. The summary
      estimate for dizygotic twins was 1.3 (1.0-1.7) and for monozygotic or same sex
      twins 1.4 (1.2-1.8).

PMID- 18071361
TI  - Population attributable fractions for ovarian cancer in Swedish women by
      morphological type.
AB  - Using the Swedish Family-Cancer Database, among a total of 1,030,806 women
      followed from 1993 through 2004, invasive and borderline epithelial ovarian
      cancer was identified in 3306 and 822 women respectively, with data on family
      history, reproductive variables, residential region and socioeconomic status.
      Relative risks and population-attributable fractions (PAFs) were estimated by
      Poisson regression. The overall PAFs of invasive epithelial ovarian cancer for
      family history and for reproductive factors were 2.6 and 22.3%, respectively, for
      serous/seropapillary cystadenocarcinoma (3.0 and 19.1%), endometrioid carcinoma
      (2.6 and 26.6%), mucinous cystadenocarcinoma (0.5 and 23.9%) and clear-cell
      carcinoma (2.6 and 73.9%). The corresponding PAFs of borderline tumours due to
      family history were lower, but higher due to reproductive factors. Family
      history, low parity and young age at first birth were associated with elevated
      risks. The risks for women with a family history were among the highest, but
      these women accounted for the smallest proportion of the cases, giving the lowest
      PAFs.

PMID- 18071362
TI  - Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal
      imbalances using array comparative genomic hybridisation.
AB  - The initiating somatic genetic events in chordoma development have not yet been
      identified. Most cytogenetically investigated chordomas have displayed near
      diploid or moderately hypodiploid karyotypes, with several numerical and
      structural rearrangements. However, no consistent structural chromosome
      aberration has been reported. This is the first array-based study characterising
      DNA copy number changes in chordoma. Array comparative genomic hybridisation
      (aCGH) identified copy number alterations in all samples and imbalances affecting
      5 or more out of the 21 investigated tumours were seen on all chromosomes. In
      general, deletions were more common than gains and no high-level amplification
      was found, supporting previous findings of primarily losses of large chromosomal
      regions as an important mechanism in chordoma development. Although small
      imbalances were commonly found, the vast majority of these were detected in
      single cases; no small deletion affecting all tumours could be discerned.
      However, the CDKN2A and CDKN2B loci in 9p21 were homo- or heterozygously lost in
      70% of the tumours, a finding corroborated by fluorescence in situ hybridisation,
      suggesting that inactivation of these genes constitute an important step in
      chordoma development.

PMID- 18071363
TI  - Characterisation and protein expression profiling of annexins in colorectal
      cancer.
AB  - The annexins are family of calcium-regulated phospholipid-binding proteins with
      diverse roles in cell biology. Individual annexins have been implicated in tumour
      development and progression, and in this investigation a range of annexins have
      been studied in colorectal cancer. Annexins A1, A2, A4 and A11 were identified by
      comparative proteomic analysis to be overexpressed in colorectal cancer. Annexins
      A1, A2, A4 and A11 were further studied by immunohistochemistry with a colorectal
      cancer tissue microarray containing primary and metastatic colorectal cancer and
      also normal colon. There was significant increase in expression in annexins A1
      (P=0.01), A2 (P<0.001), A4 (P<0.001) and A11 (P<0.001) in primary tumours
      compared with normal colon. There was increasing expression of annexins A2
      (P=0.001), A4 (P=0.03) and A11 (P=0.006) with increasing tumour stage. An annexin
      expression profile was identified by k-means cluster analysis, and the annexin
      profile was associated with tumour stage (P=0.01) and also patient survival.
      Patients in annexin cluster group 1 (low annexin expression) had a better
      survival (log rank=5.33, P=0.02) than patients in cluster group 2 (high annexins
      A4 and A11 expression). In conclusion, this study has shown that individual
      annexins are present in colorectal cancer, specific annexins are overexpressed in
      colorectal cancer and the annexin expression profile is associated with survival.

PMID- 18071364
TI  - Constitutive expression of pathogen-inducible OsWRKY31 enhances disease
      resistance and affects root growth and auxin response in transgenic rice plants.
AB  - WRKY transcription factors have many regulatory roles in response to biotic and
      abiotic stresses. In this study, we isolated a rice WRKY gene (OsWRKY31) that is
      induced by the rice blast fungus Magnaporthe grisea and auxin. This gene encodes
      a polypeptide of 211 amino-acid residues and belongs to a subgroup of the rice
      WRKY gene family that probably originated after the divergence of monocot and
      dicot plants. OsWRKY31 was found to be localized to the nucleus of onion
      epidermis cells to transiently express OsWRKY31-eGFP fusion protein. Analysis of
      OsWRKY31 and its mutants fused with a Gal4 DNA-binding domain indicated that
      OsWRKY31 has transactivation activity in yeast. Overexpression of the OsWRKY31
      gene was found to enhance resistance against infection with M. grisea, and the
      transgenic lines exhibited reduced lateral root formation and elongation compared
      with wild-type and RNAi plants. The lines with overexpression showed constitutive
      expression of many defense-related genes, such as PBZ1 and OsSci2, as well as
      early auxin-response genes, such as OsIAA4 and OsCrl1 genes. Furthermore, the
      plants with overexpression were less sensitive to exogenously supplied IBA, NAA
      and 2,4-D at high concentrations, suggesting that overexpression of the OsWRKY31
      gene might alter the auxin response or transport. These results also suggest that
      OsWRKY31 might be a common component in the signal transduction pathways of the
      auxin response and the defense response in rice.

PMID- 18071365
TI  - Enrichment of putative human epidermal stem cells based on cell size and collagen
      type IV adhesiveness.
AB  - The enrichment and identification of human epidermal stem cells (EpSCs) are of
      paramount importance for both basic research and clinical application. Although
      several approaches for the enrichment of EpSCs have been established, enriching a
      pure population of viable EpSCs is still a challenging task. An improved approach
      is worth developing to enhance the purity and viability of EpSCs. Here we report
      that cell size combined with collagen type IV adhesiveness can be used in an
      improved approach to enrich pure and viable human EpSCs. We separated the rapidly
      adherent keratinocytes into three populations that range in size from 5-7 microm
      (population A), to 7-9 microm (population B), to > or =9 microm (population C) in
      diameter, and found that human putative EpSCs could be further enriched in
      population A with the smallest size. Among the three populations, population A
      displayed the highest density of beta1-integrin receptor, contained the highest
      percentage of cells in G0/G1 phase, showed the highest nucleus to cytoplasm
      ratio, and possessed the highest colony formation efficiency (CFE). When injected
      into murine blastocysts, these cells participated in multi-tissue formation. More
      significantly, compared with a previous approach that sorted putative EpSCs
      according to beta1-integrin antibody staining, the viability of the EpSCs
      enriched by the improved approach was significantly enhanced. Our results provide
      a putative strategy for the enrichment of human EpSCs, and encourage further
      study into the role of cell size in stem cell biology.

PMID- 18071366
TI  - Derivation of human embryonic stem cell lines from parthenogenetic blastocysts.
AB  - Parthenogenesis is one of the main, and most useful, methods to derive embryonic
      stem cells (ESCs), which may be an important source of histocompatible cells and
      tissues for cell therapy. Here we describe the derivation and characterization of
      two ESC lines (hPES-1 and hPES-2) from in vitro developed blastocysts following
      parthenogenetic activation of human oocytes. Typical ESC morphology was seen, and
      the expression of ESC markers was as expected for alkaline phosphatase, octamer
      binding transcription factor 4, stage-specific embryonic antigen 3, stage
      specific embryonic antigen 4, TRA-1-60, and TRA-1-81, and there was absence of
      expression of negative markers such as stage-specific embryonic antigen 1.
      Expression of genes specific for different embryonic germ layers was detected
      from the embryoid bodies (EBs) of both hESC lines, suggesting their
      differentiation potential in vitro. However, in vivo, only hPES-1 formed teratoma
      consisting of all three embryonic germ layers (hPES-2 did not). Interestingly,
      after continuous proliferation for more than 100 passages, hPES-1 cells still
      maintained a normal 46 XX karyotype; hPES-2 displayed abnormalities such as
      chromosome translocation after long term passages. Short Tandem Repeat (STR)
      results demonstrated that the hPES lines were genetic matches with the egg
      donors, and gene imprinting data confirmed the parthenogenetic origin of these ES
      cells. Genome-wide SNP analysis showed a pattern typical of parthenogenesis. All
      of these results demonstrated the feasibility to isolate and establish human
      parthenogenetic ESC lines, which provides an important tool for studying
      epigenetic effects in ESCs as well as for future therapeutic interventions in a
      clinical setting.

PMID- 18071367
TI  - Apoptosis commitment--translating survival signals into decisions on
      mitochondria.
AB  - Most defective and unwanted cells die by apoptosis, an exquisitely controlled
      genetic programme for removing such cells without damaging the surrounding
      tissue. Once a cell has committed to apoptosis, the process is remarkably
      efficient, and is completed within a few minutes of initiation. This point of no
      return for an apoptotic cell is commonly held to be the point at which the outer
      mitochondrial membrane is permeabilised, a process regulated by the Bcl-2 family
      of proteins. How these proteins regulate this decision point is central to
      diseases such as cancer where apoptotic control is lost. In this review, we will
      discuss apoptotic signalling and how a cell makes the irreversible decision to
      die. We will focus on one set of survival signals, those derived by cell adhesion
      to the extracellular matrix (ECM), and use these to highlight the complexities of
      apoptotic signalling. In particular, we will illustrate how multiple signalling
      pathways converge to determine critical cell fate decisions.

PMID- 18071368
TI  - Network search method in the design of extreme ultraviolet lithographic
      objectives.
AB  - The merit function space of mirror system for extreme ultraviolet (EUV)
      lithography is studied. Local minima situated in the multidimensional optical
      merit function space are connected via links that contain saddle points and form
      a network. We present networks for EUV lithographic objective designs and discuss
      how these networks change when control parameters, such as aperture and field,
      are varied, and constraints are used to limit the variation domain of the
      variables. A good solution in a network, obtained with a limited number of
      variables, has been locally optimized with all variables to meet practical
      requirements.

PMID- 18071369
TI  - Group-velocity dispersion measurements of water, seawater, and ocular components
      using multiphoton intrapulse interference phase scan.
AB  - The use of femtosecond lasers requires accurate measurements of the dispersive
      properties of media. Here we measure the second- and third-order dispersion of
      water, seawater, and ocular components in the range of 660-930 nm using a new
      method known as multiphoton intrapulse interference phase scan. Our direct
      dispersion measurements of water have the highest precision and accuracy to date.
      We found that the dispersion for seawater increases proportionally to the
      concentration of salt. The dispersion of the vitreous humor was found to be close
      to that of water. The chromatic dispersion of the cornea-lens complex was
      measured to obtain the full dispersive properties of the eye.

PMID- 18071370
TI  - Multilayer holographic recording using a two-color-absorption photopolymer.
AB  - We developed a sensitive two-color-absorption photopolymer in which holograms are
      recorded by simultaneous irradiation with a 660 nm interference light and a 410
      nm gate light. Doped with bis(silyl)pentathiophene as a two-color-photosensitive
      dye and 2,2-dimethoxy-2-phenylacetophenone as a radical photopolymerization
      initiator; its matrix contains low-refractive index binding polymers and high
      refractive index monomers. The sensitivity and diffraction efficiency of 25 mum
      thick layers are from 1.2 x 10(-9) to 3.7 x 10(-9) cm2/mJ and from 1% to 4%. We
      made a three-photopolymer-layer waveguide structure, where each photopolymer
      layer and high-refractive index adhesive layer serves as a core layer and is
      sandwiched between two low-refractive index glass substrates that serve as clad
      layers. Gate light propagated through the adhesive layers, reference and object
      beams intersected the photopolymer layers, and different diffraction patterns
      could be written in each layer.

PMID- 18071371
TI  - Optical realization of bioinspired spiking neurons in the electron trapping
      material thin film.
AB  - A thin film of electron-trapping material (ETM), when combined with suitable
      optical bistability, is considered as a medium for optical implementation of
      bioinspired neural nets. The optical mechanism of ETM under blue light and near
      infrared exposure has the inherent ability at the material level to mimic the
      crucial components of the stylized Hodgkin-Huxley model of biological neurons.
      Combining this unique property with the high-resolution capability of ETM, a
      dense network of bioinspired neurons can be realized in a thin film of this
      infrared stimulable storage phosphor. When combined with suitable optical
      bistability and optical interconnectivity, it has the potential of producing an
      artificial nonlinear excitable medium analog to cortical tissue.

PMID- 18071372
TI  - Possibilities of warm cloud microstructure profiling with multiple-field-of-view
      Raman lidar.
AB  - The possibilities of cloud characteristics retrieval with multiple-field-of-view
      Raman lidar are considered. It has been shown that the Raman lidar return is
      sensitive to two cloud characteristics; the scattering coefficient and the
      effective droplet size. This sensitivity is studied and the optimal receiver
      fields-of-view (FOVs) for cloud sounding are recommended. The optimal FOV values
      are estimated to be approximately R/H (R, the collecting optics radius, H, the
      cloud altitude) to measure the scattering coefficient profiles, and approximately
      0.01z/H for the droplet size measurements (z, the cloud thickness). The algorithm
      based on the iterative scheme and singular value decomposition as a
      regularization procedure is presented and verified using computer simulation. The
      recommendations for profile retrieval with variable altitude resolution are
      given.

PMID- 18071373
TI  - Dual-photoelastic-modulator-based polarimetric imaging concept for aerosol remote
      sensing.
AB  - A dual-photoelastic-modulator- (PEM-) based spectropolarimetric camera concept is
      presented as an approach for global aerosol monitoring from space. The most
      challenging performance objective is to measure degree of linear polarization
      (DOLP) with an uncertainty of less than 0.5% in multiple spectral bands, at
      moderately high spatial resolution, over a wide field of view, and for the
      duration of a multiyear mission. To achieve this, the tandem PEMs are operated as
      an electro-optic circular retardance modulator within a high-performance
      reflective imaging system. Operating the PEMs at slightly different resonant
      frequencies generates a beat signal that modulates the polarized component of the
      incident light at a much lower heterodyne frequency. The Stokes parameter ratio q
      = Q/I is obtained from measurements acquired from each pixel during a single
      frame, providing insensitivity to pixel responsivity drift and minimizing
      polarization artifacts that conventionally arise when this quantity is derived
      from differences in the signals from separate detectors. Similarly, u = U/I is
      obtained from a different pixel; q and u are then combined to form the DOLP. A
      detailed accuracy and tolerance analysis for this polarimeter is presented.

PMID- 18071374
TI  - Fluorescence reabsorption calculation and influence on solid-state optical
      cooling.
AB  - The calculation model of fluorescence reabsorption and reemission with
      consideration of reflection on the boundary and material size using Monte Carlo
      method is proposed. To validate this stochastic model, experiments were
      conducted, and the calculated steady state spectra showed a good agreement with
      measurements. Using the absorption and fluorescence spectra of Yb-doped phosphate
      glass by careful measurements and corrections, we calculated the redshift in the
      observed fluorescence spectra and external quantum efficiency caused by
      fluorescence reabsorption and re-emission for the samples with the geometries of
      cylinder and cuboid. The calculation results show that the fluorescence
      reabsorption and re-emission have significant influence on the cooling
      efficiency. The calculation results also show that the cylinder with small waist
      beam incident (the incident light beam diameter is much less than the size of the
      sample, and goes through the center of the sample) is suitable for optical
      cooling.

PMID- 18071375
TI  - Estimation of optical constants from multiple-scattered light using
      approximations for single particle scattering characteristics.
AB  - The inversion of multiple-scattered light measurements to extract the optical
      constant (complex refractive index) is computationally intensive. A significant
      portion of this time is due to the effort required for computing the single
      particle characteristics (absorption and scattering cross sections, anisotropy
      factor, and the phase function). We investigate approximations for computing
      these characteristics so as to significantly speed up the calculations without
      introducing large inaccuracies. Two suspensions of spherical particles viz.,
      polystyrene and poly(methyl methacrylate) were used for this investigation. It
      was found that using the exact Mie theory to compute the absorption and
      scattering cross sections and the anisotropy factor with the phase function
      computed using the Henyey-Greenstein approximation yielded the best results.
      Analysis suggests that errors in the phase functions and thus in the estimated
      optical constants depend mainly on how closely the approximations match the Mie
      phase function at small scattering angles.

PMID- 18071376
TI  - Fiber loop mirror-based optical transmissivity and optical phase retardation
      measurement architecture.
AB  - We introduce and experimentally demonstrate a fiber-connectorized optical system
      based on the use of a fiber-loop mirror (FLM) to study both the optical
      transmissivity and the optical phase retardation of a material. Our approach to
      investigating the optical transmissivity of a test sample is by initially
      adjusting the optical powers at both FLM output ports to the extremum. A
      reference and the test sample are then placed one by one at one of the FLM output
      ports. For the optical phase retardation measurement, we propose placing a test
      sample inside the FLM and analyzing the ratio of the normalized optical powers
      from the two FLM output ports in order to eliminate the effect of unwanted
      optical losses. Our experimental proof of concept using three known zero-order
      wave plates as our test samples shows promising results that agree very well with
      our theoretical analysis. Key features include robustness, low optical loss, low
      polarization dependent loss, and ease of implementation.

PMID- 18071377
TI  - Analysis of a scanning pentaprism system for measurements of large flat mirrors.
AB  - The optical surface of a large optical flat can be measured using an
      autocollimator and scanning pentaprism system. The autocollimator measures the
      slope difference between a point on the mirror and a reference point. Such a
      system was built and previously operated at the University of Arizona. We discuss
      refinements that were made to the hardware, the alignment procedure, and the
      error analysis. The improved system was demonstrated with a 1.6 m flat mirror,
      which was measured to be flat to 12 nm rms. The uncertainty in the measurement is
      only 9 nm rms.

PMID- 18071378
TI  - Optimization of off-null ellipsometry for air/solid interfaces.
AB  - The optimization of off-null ellipsometry is described with emphasis on the
      improvement of sample thickness sensitivity. Optimal conditions are dependent on
      azimuth angle settings of the polarizer, compensator, and analyzer in a polarizer
      compensator-sample-analyzer ellipsometer arrangement. Numerical simulation
      utilized offers an approach to present the dependence of the sensitivity on the
      azimuth angle settings, from which optimal settings corresponding to the best
      sensitivity are derived. For a series of samples of SiO2 layer (thickness in the
      range of 1.8-6.5 nm) on silicon substrate, the theory analysis proves that
      sensitivity at the optimal settings is increased 20 times compared to that at
      null settings used in most works, and the relationship between intensity and
      thickness is simplified as a linear type instead of the original nonlinear type,
      with the relative error reduced to approximately 1/100 at the optimal settings.
      Furthermore the discussion has been extended toward other factors affecting the
      sensitivity of the practical system, such as the linear dynamic range of the
      detector, the signal-to-noise ratio and the intensity from the light source, etc.
      Experimental results from the investigation of SiO2 layer on silicon substrate
      are chosen to verify the optimization.

PMID- 18071379
TI  - Hybrid sampling approach for imaging Fourier-transform spectrometry.
AB  - A new approach to interferogram sampling is demonstrated for Fourier-transform
      spectrometry. Sampling of the infrared channel is triggered at equidistant
      optical path differences while samples are time-referenced with a high-resolution
      digital clock. This hybrid method exploits the advantages of both time and
      position-sampling techniques. It minimizes the dataload while allowing a
      postcorrection scheme to remove sampling errors. It is therefore highly adapted
      to imaging spectrometers designed for massively parallel spatial sampling. Also,
      this technique is particularly interesting for spectrometers equipped with an
      integrating detector, such as a CCD camera, since it can account for the
      inevitable delay caused by camera integration.

PMID- 18071380
TI  - Efficient temporal shaping of ultrashort pulses with birefringent crystals.
AB  - We report on a simple and robust technique to temporally shape ultrashort pulses.
      A number of birefringent crystals with appropriate crystal length and orientation
      form a crystal set. When a short pulse propagates through the crystal set, the
      pulse is divided into numerous pulses, producing a desired temporal shape.
      Flexibility in the final pulse shape is achieved through varying initial pulse
      duration, divided-pulse number, the polarization-mode delay, and energy
      distribution of the divided pulses. The energy efficiency of the technique is
      near 100% for a pulse train of alternating polarizations, and 50% for a linearly
      polarized pulse train.

PMID- 18071381
TI  - Dispersion and birefringence of irregularly microstructured fiber with an
      elliptic core.
AB  - We have investigated the dispersion and birefringence of an irregularly
      microstructured fiber with an elliptic silica core and irregular airholes. The
      polarization-dependent output power through the fiber reveals two well-defined
      principal-axis modes despite the irregularity of airholes. The dispersion of the
      fiber is measured in the range of 680 to 1000 nm using the Mach-Zehnder
      interferometric technique with sub-10 fs laser pulses, which yield two zero
      dispersion wavelengths at 683 and 740 nm for the two principal modes,
      respectively. The birefringence measured using the wavelength scanning method is
      about 0.0055 at 800 nm. It is also demonstrated that this irregularly
      microstructured fiber with high birefringence and short zero dispersion
      wavelength is useful for the one-octave-spanning supercontinuum generation
      suitable for an f-2f interferometric system.

PMID- 18071382
TI  - Analytical model of spectrometer-based two-beam spectral interferometry.
AB  - We report an analytical model of signal formation in spectrometer-based two-beam
      spectral interferometry. Considering the pixel size, the optical resolution and
      the spectral resolution of the spectrometer, and dispersion, the model represents
      the signal recorded by a spectrometer based on a diffraction grating and linear
      detector array. The model is general, but degenerates to more familiar forms with
      simplifying assumptions. The model is validated by comparison with experimental
      measurements, where it is shown that the model can accurately predict both signal
      fall-off and axial resolution for Fourier-domain optical coherence tomography
      imaging. The model may be useful for determining design specifications and
      expected performance parameters for spectrometers for spectral interferometry.

PMID- 18071383
TI  - Fiber-based multispeckle detection for time-resolved diffusing-wave spectroscopy:
      characterization and application to blood flow detection in deep tissue.
AB  - We present a technique for the measurement of temporal field autocorrelation
      functions of multiply scattered light with subsecond acquisition time. The setup
      is based on the parallel detection and autocorrelation of intensity fluctuations
      from statistically equivalent but independent speckles using a fiber bundle, an
      array of avalanche photodiodes, and a multichannel autocorrelator with variable
      integration times between 6.5 and 104 ms. Averaging the autocorrelation functions
      from the different speckles reduces the integration time in diffusing-wave
      spectroscopy experiments drastically, thus allowing us to resolve nonstationary
      scatterer dynamics with single-trial measurements. We present applications of the
      technique to the measurement of arterial and venous blood flow in deep tissue. We
      find strong deviations both of the shape and characteristic decay time of
      autocorrelation functions recorded at different phases of the pulsation cycle
      from time-averaged autocorrelation functions.

PMID- 18071384
TI  - Photoconductive arrays for monitoring motion of spatial optical intensity
      patterns.
AB  - We describe a photodetector array based on photoconductance-monitoring by four
      point probing. This detection scheme is aimed specifically at detecting changes
      within a speckle or microscopic fringes within a larger nonuniform optical
      intensity distribution. One specific application is the detection of lateral
      displacements of these speckles or fringes, for example, in laser light reflected
      from optically rough vibrating surfaces. With a prototype, we have detected
      subnanometer surface displacements interferometrically. We also demonstrate
      speckle-based, noninterferometric detection of a guitar body's vibrations at a
      standoff distance of 6 m with nanowatt power. We observe and explain the
      prototype's limited frequency response by considering space-charge effects. This
      detection scheme is most useful in low-power, low-frequency applications.

PMID- 18071386
TI  - Improved method for calibrating a Stokes polarimeter.
AB  - We present a method for calibrating a polarization state analyzer that uses a set
      of well- characterized reference polarization states and makes no assumptions
      about the optics contained in the polarimeter other than their linearity. The
      method requires that a matrix be constructed that contains the data acquired for
      each of the reference polarization states and that this matrix be pseudoinverted.
      Since this matrix is usually singular, we improve the method by performing the
      pseudoinversion by singular value decomposition, keeping only the four largest
      singular values. We demonstrate the calibration technique using an imaging
      polarimeter based upon liquid crystal variable retarders and with light emitting
      diode (LED) illumination centered at 472 nm, 525 nm, and 630 nm. We generate the
      reference polarization states by using an unpolarized source, a single polarizer,
      and a Fresnel rhomb. This method is particularly useful when calibrations are
      performed on field-grade instruments at a centrally maintained facility and when
      a traceability chain needs to be maintained.

PMID- 18071385
TI  - Properties of microlenses produced on a layer of tot'hema and eosin sensitized
      gelatin.
AB  - Gelatin sensitized with tot'hema and eosin (compounds used in medical therapy)
      appears to be an excellent material for microlens fabrication. Lenses are
      produced by irradiation with a 532 nm laser beam. Aspheric concave lenses are
      formed rapidly with low power radiation. The lens profile is analyzed, as well as
      imaging properties. Physics of lens formation is also proposed. All material
      constituents are nonpoisonous, resulting in an environmentally safe, low toxicity
      material.

PMID- 18071387
TI  - Dual-aureole and sun spectrometer system for airborne measurements of aerosol
      optical properties.
AB  - We have designed an airborne spectrometer system for the simultaneous measurement
      of the direct sun irradiance and the aureole radiance in two different solid
      angles. The high-resolution spectral radiation measurements are used to derive
      vertical profiles of aerosol optical properties. Combined measurements in two
      solid angles provide better information about the aerosol type without additional
      and elaborate measuring geometries. It is even possible to discriminate between
      absorbing and nonabsorbing aerosol types. Furthermore, they allow to apply
      additional calibration methods and simplify the detection of contaminated data
      (e.g., by thin cirrus clouds). For the characterization of the detected aerosol
      type a new index is introduced that is the slope of the aerosol phase function in
      the forward scattering region. The instrumentation is a flexible modular setup,
      which has already been successfully applied in airborne and ground-based field
      campaigns. We describe the setup as well as the calibration of the instrument. In
      addition, example vertical profiles of aerosol optical properties--including the
      aureole measurements--are shown and discussed.

PMID- 18071388
TI  - Real-time Fourier transformer based on fiber gratings.
AB  - We use the well-known duality between paraxial diffraction in space and
      dispersion in time to propose a time-domain analog to spatial Fraunhofer
      diffraction. This analog permits the design of real-time optical Fourier
      transformer systems. These systems are shown to be realizable by use of linearly
      chirped fiber gratings as dispersive media.

PMID- 18071389
TI  - High-intensity third-harmonic generation in beta barium borate through second
      order and third-order susceptibilities.
AB  - The azimuthal dependence of third-order and cascaded second-order nonlinear
      coupling was used to measure the relative contributions of each to direct third
      harmonic generation in beta-barium borate. This permitted the measurement of the
      values of tensor elements chi(3)(10) , chi(3)(11) , and chi(3)(16) relative to
      the known chi(2)(ij) . Finally, conversion efficiencies to 3 omega of up to 6%
      were achieved with a femtosecond chirped-pulse amplification laser with 200
      GW/cm(2) in collimated beams.

PMID- 18071390
TI  - Spatial switching of quadratic solitons in engineered quasi-phase-matched
      structures.
AB  - We show that a variety of quasi-phase-matched structures with engineered patterns
      can potentially be used for soliton control in quadratic nonlinear media. We
      study geometries with dislocations, tilts, and wells and predict spatial
      switching between different output soliton states. Experimental implementation
      conditions are discussed.

PMID- 18071391
TI  - Phase conjugation with random fields and with deterministic and random
      scatterers.
AB  - The theory of distortion correction by phase conjugation, developed since the
      discovery of this phenomenon many years ago, applies to situations when the field
      that is conjugated is monochromatic and the medium with which it interacts is
      deterministic. In this Letter a generalization of the theory is presented that
      applies to phase conjugation of partially coherent waves interacting with either
      deterministic or random weakly scattering nonabsorbing media.

PMID- 18071392
TI  - Effect of dissipative forces on the theory of a single-atom microlaser.
AB  - A single-atom microlaser involving Poissonian input of atoms with a fixed flight
      time through an optical resonator is described. The influence of the cavity
      reservoir during the interactions of successive individual atoms with the cavity
      field is included in the analysis. Atomic decay is also considered, as it is
      nonnegligible in the optical regime. During the random intervals of absence of
      any atom in the cavity, the field evolves under its own dynamics. The steady
      state characteristics of the cavity field are discussed. Away from laser
      threshold, the field can be nonclassical in nature.

PMID- 18071393
TI  - Accurate relative frequency cancellation between two independent lasers.
AB  - For high-precision frequency-based applications of lasers, the frequency
      difference between two independent lasers is accurately stabilized and
      maintained. We describe a simple and novel feed-forward method with an acousto
      optic modulator. This method can be used in optical phase-locked loops.

PMID- 18071394
TI  - Continuous-wave broadly tunable Cr2+:ZnSe laser.
AB  - We report room-temperature operation of an all-solid-state broadly tunable
      continuous-wave Cr(2+):ZnSe laser. Output power of 250 mW, an absorbed power
      slope efficiency of 63%, and continuous tunability from 2138 to 2760 nm are
      demonstrated.

PMID- 18071395
TI  - Temporal behavior of an unstable optical cavity.
AB  - The relaxation of a geometrically unstable Fabry-Perot cavity is theoretically
      and experimentally investigated. It is observed that the usual sum of the
      exponential decays of the intensities in the different transverse modes of the
      cavity is replaced by a more complex behavior. In particular, light couplings
      into the fundamental mode of the cavity with initial wave excitation factors
      larger than unity, i.e., larger than in the case of mode-matched injection, are
      directly observed. The influence of the cavity Fresnel number and of transverse
      mode crossings and anticrossings on these cavity decays is isolated.

PMID- 18071396
TI  - Superluminal terahertz pulses.
AB  - In femtosecond terahertz-pulse (T-ray) imaging of metal structures with
      dimensions of the order of the wavelength, it is observed that the T rays
      propagate faster than the vacuum speed of light. In the case of apertures this
      can be understood as a waveguide effect in which superluminal velocities are
      expected close to the cutoff frequency. However, the effect is also observed
      close to knife edges and in propagation past thin metal wires.

PMID- 18071397
TI  - Generation of femtosecond pulses from order-of-magnitude pulse compression in a
      synchronously pumped optical parametric oscillator based on periodically poled
      lithium niobate.
AB  - We demonstrate the generation of compressed, transform-limited 250-fs pulses,
      tunable in the near infrared, by means of synchronously pumped optical parametric
      oscillation in periodically poled lithium niobate. The almost 20-fold compression
      from the 4-ps pulse duration of the cw mode-locked Nd:YLF pump results in signal
      peak powers well in excess of the pump power.

PMID- 18071398
TI  - Dispersion compensation for a femtosecond self-pumped phase conjugator.
AB  - Dispersion compensation for a photorefractive self-pumped phase conjugator with
      femtosecond pulses is analyzed. The self-pumped phase conjugator consists of a
      pair of dynamic gratings coupled by total internal reflections at the crystal
      surfaces (cat conjugator). The negative angular dispersions of refraction at the
      air-crystal interface and the gratings inside the crystal compensate for the
      positive dispersion of the finite crystal path. The experimental results show
      that with partial dispersion compensation the width of the self-pumped phase
      conjugation at 450 nm of femtosecond pulses is narrower than that of the
      transmitted pulses.

PMID- 18071399
TI  - Generation of intense 8-fs pulses at 400 nm.
AB  - Frequency-doubled pulses from a sub-40-fs, 1-kHz Ti:sapphire amplifier system are
      spectrally broadened in an argon-filled hollow waveguide. Compression of the self
      phase-modulated pulses is implemented with chirped mirrors and a prism pair,
      yielding 8-fs, 15-muJ pulses in the violet spectral range.

PMID- 18071400
TI  - Regeneration of photon echoes with amplified photon echoes.
AB  - Photon-echo-based devices have been proposed for many applications in data
      storage, image processing, and optical communications. Many of these applications
      would benefit if the output from the photon-echo process could be used as input
      in a second photon-echo process. We demonstrate the generation of such secondary
      echoes, using the amplified output from an initial photon-echo process. The
      amplification is performed with a Pr:ZBLAN fiber amplifier, which gives a gain of
      more than 300 at 606 nm when pumped with 320 mW of power at 476 nm.

PMID- 18071401
TI  - Wideband deep penetration of photon-number fluctuations into the quantum regime
      in series-coupled light-emitting diodes.
AB  - Experimental results on the squeezing of photon-number fluctuations of series
      coupled LED's driven by a constant-voltage source are presented that illustrate
      the advantage of series-coupled LED's, namely, a greater squeezing capability
      than that of a single LED driven through an equivalent series resistor. We
      discuss the microscopic origin of the deep squeezing on the basis of quantum
      mechanical Langevin equations.

PMID- 18071402
TI  - Perturbation theory of quantum solitons: continuum evolution and optimum
      squeezing by spectral filtering.
AB  - We study the quantum-noise properties of spectrally filtered solitons in optical
      fibers. Perturbation theory, including a quantum description of the continuum, is
      used to derive a complete analytical expression for the second-order correlator
      of the amplitude quadrature. This correlator is subsequently used to optimize the
      frequency response of the filter numerically in order to achieve the minimum
      photon-number noise. For propagation distances up to three soliton periods, the
      length at which the best noise reduction occurs, a square filter is found to be
      approximately optimum. For longer distances, more-complicated filter shapes are
      predicted for the best noise reduction.

PMID- 18071403
TI  - Silica-air photonic crystal fiber design that permits waveguiding by a true
      photonic bandgap effect.
AB  - A theoretical investigation of a novel type of optical fiber is presented. The
      operation of the fiber relies entirely on wave guidance through the photonic
      bandgap effect and not on total internal reflection, thereby distinguishing that
      fiber from all other known fibers, including recently studied photonic crystal
      fibers. The novel fiber has a central low-index core region and a cladding
      consisting of a silica background material with air holes situated within a
      honeycomb lattice structure. We show the existence of photonic bandgaps for the
      silica-air cladding structure and demonstrate how light can be guided at the
      central low-index core region for a well-defined frequency that falls inside the
      photonic bandgap region of the cladding structure.

PMID- 18071404
TI  - Three-dimensional photonic crystal with a stop band from 1.35 to 1.95 microm.
AB  - A combination of advanced silicon-processing techniques was used to create three
      dimensional (3D) photonic crystals with a 180-nm minimum feature size. The
      resulting 3D crystal displayed a strong stop band at optical wavelengths from
      lambda=1.35 microm to lambda=1.95 microm . This is believed to be the smallest 3D
      crystal with a complete 3D photonic bandgap ever created.

PMID- 18071405
TI  - Spectral holography for coherence-gated imaging.
AB  - A spectral-holography application called spectral-decomposition holography forms
      a recorded image according to optical path length. In this method all wavelength
      components of a broad-spectrum source simultaneously backlight a nonscattering
      binary-phase object. A spectral hologram is thus recorded. Subsequent computer
      processing recovers temporally discriminated images.

PMID- 18071406
TI  - Fabry Perot etalon with polymer cholesteric liquid-crystal mirrors.
AB  - We present what we believe to be the first implementation of a Fabry-Perot (FP)
      etalon using polymer cholesteric liquid-crystal mirrors. These polymer mirrors
      have each been fabricated onto a single substrate, which allows the FP cavity
      spacing to be only a few micrometers wide. For the experimental results
      presented, cavity lengths of 13.8 and 7.6 microm yield near-infrared free
      spectral ranges of 24.8 and 45.6 nm, respectively. The measured finesse of 14.31
      is approaching the limitation imposed by the reflectivity of the mirrors.

PMID- 18071407
TI  - Excimer-laser-induced degradation of fused silica and calcium fluoride for 193-nm
      lithographic applications.
AB  - We report the initial results of a large-scale evaluation of production-grade
      fused silica and calcium fluoride to be used in 193-nm lithographic applications.
      The samples have been provided by many different suppliers of materials. A
      marathon irradiation chamber permits simultaneous exposure of as many as 36
      samples at 800 Hz, at fluences from 0.2 to > or =4 (mJ/cm(2))/pulse and pulse
      counts in excess of 10(9) . The initial absorption and the laser-induced
      absorption are found to vary over a wide range. The compaction of each fused
      silica sample follows a power law, but its parameters can differ widely from
      sample to sample.

PMID- 18071408
TI  - Single-pass measurements of the wave-front aberrations of the human eye by use of
      retinal lipofuscin autofluorescence.
AB  - We describe a technique for making single-pass measurements of the wave-front
      aberration of the eye. The technique utilizes the natural fluorescence of the
      retina that is produced by lipofuscin to form an incoherent pointlike source for
      conventional Shack-Hartmann sensing.

PMID- 18071409
TI  - Double-pass imaging polarimetry in the human eye.
AB  - A Mueller-matrix imaging polarimeter was developed to measure spatially resolved
      polarization properties in the living human eye. The apparatus is a double-pass
      setup that incorporates two liquid-crystal variable retarders and a slow-scan CCD
      camera in the recording stage. Series of 16 images for the combinations of
      independent polarization states in the first and second passages were recorded
      for two experimental conditions: with the camera conjugated either with the
      retina or with the eye's pupil plane. Spatially resolved collections of Mueller
      matrices and the degree of polarization were calculated from those images for
      both retinal and pupil planes.

PMID- 18071410
TI  - Curing of dental composites by use of InGaN light-emitting diodes.
AB  - A potential application of blue-light-emitting InGaN LED's as a polymerizing
      source for dental composite materials is described. We compared a basic LED
      device with a conventional curing light in vitro to determine the polymerization
      parameters and to examine the effect of the curing process on the physical
      properties of these materials. It was determined that an array of six LED's was
      able to set a range of composite materials more quickly than a conventional light
      source, with the cured compounds showing similar hardness and material shrinkage
      parameters but with a lower material temperature rise during the curing process
      using the array. These findings indicate that a device consisting of several
      InGaN LED's would be an effective instrument for curing certain light-sensitive
      materials, particularly dental composites.

PMID- 18071411
TI  - Diffraction from metallic gratings with locally varying profile forms.
AB  - Measurements of the diffraction characteristics of one-dimensional surface-relief
      gratings of locally varying profile are compared with rigorous diffraction
      theory. These gratings result from the superposition of two linear sinusoidal
      gratings of uniform depth for which the relative phase between the two gratings
      varies slowly with position. The resultant surface profile exhibits a relatively
      large-period variation in profile form. The periodic variation in diffraction
      efficiency that results yields a visual moire pattern that has interesting
      asymmetry and polarization properties that alter as the viewing conditions are
      changed; the gratings can be exploited by diffractive optically variable devices
      for document security.

PMID- 18071412
TI  - Image enhancement in near-field scanning optical microscopy with laser-trapped
      metallic particles.
AB  - A trapped-particle near-field scanning optical microscope is constructed by use
      of submicrometer- or micrometer-sized metallic particles (gold and silver) to
      increase scattering efficiency. The image contrast of the evanescent-wave
      interference pattern on the surface of a prism upon total internal reflection,
      obtained with trapped gold particles of diameter 0.1 and 2microm , is improved by
      a factor of approximately 2 and 1.5, respectively, compared with that obtained
      with trapped polystyrene particles of similar size. The use of a 2-microm gold
      particle leads to image contrast that is approximately three times as great as
      that obtained with a 0.1-microm gold particle, and interference patterns of a
      subwavelength period are obtained in both cases.

PMID- 18071413
TI  - Fixing the photorefractive soliton.
AB  - We report the formation of permanent two-dimensional 12-microm waveguides in a
      bulk strontium barium niobate crystal. The waveguides are made by formation of a
      photorefractive spatial soliton in which the space-charge field induces
      ferroelectric domains that are permanently polarized opposite to the crystal c
      axis. The fixed waveguide propagates light with 80% efficiency. These results
      make possible the permanent recording of intricate optical circuitry in the
      volume of a bulk crystal.

PMID- 18071414
TI  - Competition between modulational instability and switching in optical
      bistability.
AB  - We study theoretically and experimentally the switching dynamics of a nonlinear
      optical bistable system that exhibits modulational instability in the vicinity of
      its lower limit point. We show that modulational instability induces premature
      upswitching and, in this way, truncates the bistable cycle. The role of the
      modulation instability is identified experimentally through the observation of
      the transient pattern formation that precedes upswitching. Our experiment
      illustrates the importance of cooperative behavior in practical distributed
      bistable systems.

PMID- 18071415
TI  - One-dimensional quadratic walking solitons.
AB  - The properties of one-dimensional quadratic walking solitons were investigated in
      planar lithium niobate waveguides near the type I phase-matching condition for
      second-harmonic generation. Wave propagation was studied under different
      conditions of phase matching, walk-off angle, and incident fundamental power.

PMID- 18071416
TI  - Enhancement of four-wave mixing and line narrowing by use of quantum coherence in
      an optically dense double-? solid.
AB  - We have demonstrated enhanced nondegenerate four-wave mixing by use of a resonant
      probe in a double- ? system consisting of an optically dense spectral hole
      burning solid. The observed probe diffraction efficiency is ~16% in amplitude at
      6 K, which is higher than for an off-resonant probe in a ? -type scheme. We have
      also observed two-photon coherence line narrowing, which has potential
      application to high-resolution spectroscopy.

PMID- 18071417
TI  - Soliton squeezing in a highly transmissive nonlinear optical loop mirror.
AB  - A perturbation approach is used to study the quantum noise of optical solitons in
      an asymmetric fiber Sagnac interferometer (a highly transmissive nonlinear
      optical loop mirror). Analytical expressions for the three second-order
      quadrature correlators are derived and used to predict the amount of detectable
      amplitude squeezing along with the optimum power-splitting ratio of the Sagnac
      interferometer. We find that it is the number-phase correlation owing to the Kerr
      nonlinearity that is primarily responsible for the observable noise reduction.
      The group-velocity dispersion affecting the field in the nonsoliton arm of the
      fiber interferometer is shown to limit the minimum achievable Fano factor.

PMID- 18071418
TI  - Tunable fiber-optic parametric oscillator.
AB  - We report operation of a tunable optical parametric oscillator that employs a
      nonlinear-fiber Sagnac interferometer as a parametric amplifier. The amplifier,
      which consists primarily of dispersion-shifted fiber that has zero dispersion at
      1538 nm, is synchronously pumped with 7.7-ps pulses at 1539 nm. The wide
      bandwidth of the parametric gain permits tuning of the output signal pulses over
      a 40-nm range centered on the pump wavelength. The Sagnac interferometer
      decouples the pump wave from the oscillator cavity while a bandpass filter in the
      cavity transmits only the signal wave, thereby creating a singly resonant
      parametric oscillator that is phase insensitive. Whereas we demonstrate tuning
      over almost the entire bandwidth of Er-doped-fiber amplifiers, one could
      construct a similar device that operates near the 1310-nm zero-dispersion
      wavelength of standard telecommunication fiber.

PMID- 18071419
TI  - Polarization control in a large-stroke optical fiber delay line.
AB  - In the context of an optical fiber delay-line implementation by use of silica
      fiber stretching capability, we experimentally demonstrate that highly
      birefringent fibers preserve their ability to maintain the polarization coherence
      in spite of the high magnitude of the stresses applied to them during large
      stretching. Two experimental demonstrations are presented. In the first,
      polarization cross coupling versus stretching is characterized. This stretching
      induces a variation of group delay in the span 0-45 cm. The second is a test of
      the fiber stretcher in an interferometric application.

PMID- 18071420
TI  - Phase-locked optical divide-by-3 system for visible radiation.
AB  - An optical divide-by-3 system has been developed to phase lock a diode-pumped
      Tm:YAG laser at 148 THz (2022 nm) to a frequency near 1/3 that of an ultrastable
      diode laser system at 445 THz (674 nm). The 148-THz radiation is frequency
      doubled in angle-tuned AgGaS(2) and frequency differenced with the 445-THz
      radiation in noncritically phase-matched LiNbO(3) , generating two signals at 297
      THz, which are mixed on a photodiode. An electronic servo system is used to
      control the frequency of the Tm:YAG laser and to phase lock it to the visible
      diode laser output. Phase-locking periods of several minutes are routinely
      obtained.

PMID- 18071421
TI  - Demonstration of transient gain x-ray lasers near 20nm for nickellike yttrium,
      zirconium, niobium, and molybdenum.
AB  - We demonstrate strong lasing on the Ni-like 4d(1)S(0)?4p(1)P(1) transition at
      18.9, 20.3, 22.0, and 24.0 nm for Mo, Nb, Zr, and Y ions, respectively, using the
      transient collisional excitation scheme. Approximately 5 J of laser energy in a
      combination of a 600-ps pulse and a 1-ps pulse from the Compact Multipulse
      Terawatt (COMET) tabletop laser system is used to irradiate slab targets of these
      materials. Small-signal gains of 17-26cm (-1) are determined on the 4d?4p
      transition, with overall gain-length products gL of 11-12. Lasing is observed and
      gain is measured on the 4f(1)P(1)?4d(1)P(1) transition, which is pumped by
      collisional excitation combined with self-photopumping, for what is to our
      knowledge the first time.

PMID- 18071422
TI  - Phase-modulation transmission system for quantum cryptography.
AB  - We describe a new method for quantum key distribution that utilizes phase
      modulation of sidebands of modulation by use of integrated electro-optic
      modulators at the transmitting and receiving modules. The system is shown to
      produce constructive or destructive interference with unity visibility, which
      should allow quantum cryptography to be carried out with high flexibility by use
      of conventional devices.

PMID- 18071424
TI  - Compact gas sensor using a pulsed difference-frequency laser spectrometer.
AB  - We present a novel compact pulsed laser spectrometer based on difference
      frequency mixing of a cw tunable external-cavity diode laser (795-825 nm) and a
      pulsed Nd:YAG laser (1064 nm) in bulk LiNbO(3) . The pulsed mid-IR source is
      continuously tunable from 3.16 to 3.67microm and exhibits a linewidth of only 154
      MHz, a peak power of approximately 50microW , and a pulse duration of 6 ns at a
      6.5-kHz repetition rate. Spectra of methane in room air and formaldehyde have
      been recorded at room-temperature operation in a multipass cell with deduced
      detection limits of 10 and 40 parts in 10(9) , respectively.

PMID- 18071423
TI  - Diffractometric methods for absolute measurement of diffraction-grating spacings.
AB  - We propose one- and two-wavelength methods of absolute measurement of diffraction
      grating spacings based on the Littman configuration for autocollimation. The one
      wavelength method has been applied to measure the spacing of a grating with a
      nominal value of 2160grooves/mm . The grating spacing was measured to be 463.16
      nm, with an experimental standard deviation of 0.24 nm. It has been demonstrated
      that the both methods can provide direct traceability in the submicrometer region
      in terms of wavelength standards for applications in the field of nanometrology.

PMID- 18071425
TI  - Pulse-length dependence of cellular response to intense near-infrared laser
      pulses in multiphoton microscopes.
AB  - The influence of the pulse length, tau , of ultrashort laser pulses at 780 and
      920 nm on cell vitality and cellular reproduction has been studied. A total of
      2400 nonlabeled cells were exposed to a highly focused scanning beam from a mode
      locked 80-MHz Ti:sapphire laser with 60-micros pixel dwell time. For the same
      pulse energy, destructive effects were more pronounced for shorter pulses. The
      damage behavior was found to follow approximately a P(2)/tau dependence (P , mean
      power), indicating that cell destruction is likely based on a two-photon
      excitation process rather than a one- or a three-photon event. Therefore,
      femtosecond as well as picosecond pulses provide approximately the same relative
      optical window for safe two-photon fluorescence microscopy.

PMID- 18071426
TI  - Single-shot fluorescence spectra of individual micrometer-sized bioaerosols
      illuminated by a 351- or a 266-nm ultraviolet laser.
AB  - Reproducible fluorescence spectra of individual 2- to 5-microm -diameter
      biological aerosol particles excited with a single shot from a Q -switched laser
      (266 or 351 nm) have been obtained with highly improved signal-to-noise ratios.
      Critical to the advance are crossed diode-laser trigger beams, which precisely
      define the sample volume, and a reflecting objective, which minimizes chromatic
      aberration and has a large N.A. for collecting fluorescence. Several allergens
      (red oak, meadow oat pollen, paper mulberry pollen, and puffball spores) have
      different fluorescence spectra. Bacillus subtilis fluorescence spectrum
      deteriorates at high 266-nm incident intensity. Dry riboflavin particles
      illuminated with a 351-nm light exhibit a new 420-nm fluorescence peak that grows
      nonlinearly with laser pulse energy.

PMID- 18071427
TI  - Homogeneous polymer blend microparticles with a tunable refractive index.
AB  - We show that homogeneous polymer blend microparticles can be prepared in situ
      from droplets of dilute solution of codissolved polymers. Provided that the
      droplet of solution is small enough (<10 mum), solvent evaporation is rapid
      enough to inhibit phase separation. Thus the polymers that are being mixed need
      not be miscible, which greatly enhances the applicability of the technique. From
      analysis of two-dimensional Fraunhofer diffraction (angular scattering) patterns,
      we show that both the real and the imaginary parts of the refractive index can be
      tuned by adjustment of the relative weight fractions of polymers in solution.

PMID- 18071428
TI  - Imaging interferometric lithography: approaching the resolution limits of optics.
AB  - The resolution limits of conventional optical lithography reflect the low-pass
      spatial-frequency [numerical aperture (NA) /lambda] filter characteristics of the
      imaging system. Imaging interferometric lithography extends the resolution of
      optical lithography to the spatial-frequency limits of optics (2/lambda) . Off
      axis illumination downshifts the high-frequency components of the mask pattern.
      An interferometric beam at the wafer upshifts these frequency components back to
      their original spatial frequencies following the lens. 2x reduction imaging
      interferometric lithography experiments demonstrate a continuous frequency
      coverage up to ~3N.A./lambda with a consequent threefold resolution enhancement.

PMID- 18071429
TI  - Backward second-harmonic and third-harmonic generation in a periodically poled
      potassium titanyl phosphate waveguide.
AB  - We observed backward second-harmonic and backward third-harmonic generation in a
      periodically poled KTiOPO(4) waveguide using nanosecond laser pulses. The highest
      conversion efficiency achieved for the backward second-harmonic generation,
      occurring at the 25th-order grating, was ~0.6% . The backward third-harmonic
      generation was the result of mixing the pump beam with the forward or the
      backward second-harmonic beam. Conversion efficiency of ~0.4% was achieved at a
      pump wavelength of 1233.7 nm, where the two constituent nonlinear processes are
      both quasi-phase matched.

PMID- 18071430
TI  - Strong beam coupling in mesogenic materials with photorefractive Bragg gratings.
AB  - Strong beam coupling was observed in mesogenic materials consisting of low- and
      high-molar-mass liquidcrystal mixtures with high concentration ratios of the
      latter type of liquid crystal. The beam-coupling effects originate in
      orientational photorefractive Bragg gratings, and a weak signal beam with an
      intensity of 1 mW is amplif ied to 8 mW by energy exchange with a strong pump
      beam after the passage of a 50-mum-thick film under a low operating voltage of 1
      4 V/ mum. There is a superior net two-beam coupling gain of more than 600 cm(-1)
      with the low operating voltage and high resolution.

PMID- 18071431
TI  - Frequency-agile kilohertz repetition-rate optical parametric oscillator based on
      periodically poled lithium niobate.
AB  - We report kilohertz repetition-rate pulse-to-pulse wavelength tuning from 3.22 to
      3.7 mum in a periodically poled lithium niobate (PPLN) optical parametric
      oscillator (OPO). Rapid tuning over 400 cm(-1) with random wavelength
      accessibility is achieved by rotation of the pump beam angle by no more than 24
      mrad in the PPLN crystal by use of an acousto-optic beam deflector. Over the
      entire tuning range, a near-transform-limited OPO bandwidth can be obtained by
      means of injection seeding with a single-frequency 1.5-mum laser diode. The
      frequency agility, high repetition rate, and narrow bandwidth of this mid-IR PPLN
      OPO make it well suited as a lidar transmitter source.

PMID- 18071432
TI  - Phase reconstruction from reflectivity in fiber Bragg gratings.
AB  - It is shown that a recently proposed phase-retrieval technique for Bragg gratings
      [Opt. Lett. 22, 93 (1997); J. Lightwave Technol. 15, 1314 (1997)] is not well
      suited for gratings with imperfections. The reconstructed group delay is in many
      cases not a more accurate estimate than the simulated group delay of the perfect,
      designed grating, independently of how small the errors in the grating structure
      are. The error in the group delay may be especially large near the zeros in the
      reflection spectrum.

PMID- 18071433
TI  - Photoinscription of Bragg gratings within a germanosilicate fiber subjected to a
      high static electric field.
AB  - The kinetics of Bragg grating growth in germanosilicate fibers subjected to a
      high static electric field are compared with those obtained without any electric
      field. The gratings were written by exposure of the fiber core to laser light at
      244 or 193 nm. These experiments gave some clues about the mechanisms responsible
      for both the photosensitivity in germanosilicate fibers and the nonlinear second
      order UV-induced susceptibility in silica glasses. The refractive-index
      modulation proved to be significantly higher in the fibers subjected to an
      electric field. Furthermore, the change in the fiber's mean effective refractive
      index as a function of exposure time was not monotonic. This evolution can be
      explained by the assumption that some electric-field-induced diffusion of
      electron trapped centers [Ge(1) and Ge(2)] from the fiber core is involved.

PMID- 18071434
TI  - Free-space fiber hybrid distributed optical cross-connect interconnect module.
AB  - We propose implementing a large-scale optical cross-connect network based on a
      free-space-fiber hybrid interconnect system. The free-space portion of the system
      is designed to handle shuffle operation of optical beams that need to intersect
      each other. The fiber portion is used to guide these signals to and from optical
      transceivers, which can be distributed at different locations. A compact and
      packaged prototype that handles 256x256 input-output channels is demonstrated.

PMID- 18071435
TI  - Optimal allocation of amplifiers in a dispersion-managed line for a wavelength
      division-multiplexed soliton transmission system.
AB  - Optimal allocation of amplifiers in a dispersion-managed line is theoretically
      derived by means of minimizing the collision-induced frequency shift in a two
      channel wavelength-division-multiplexed soliton transmission system. Almost
      complete cancellation of the frequency shift can be obtained for such a system
      with any strength of dispersion management.

PMID- 18071436
TI  - Extraction of light from sources located inside waveguide grating structures.
AB  - A crossed waveguide grating is presented that can extract the total guided-mode
      power emitted by a pointsource dipole located in the structure. Results obtained
      with rigorous numerical simulations are compared with a simple graphic analysis
      to facilitate an understanding of the far-field radiation pattern of such a
      luminescent device.

PMID- 18071437
TI  - High-power multiple-frequency narrow-linewidth laser source based on a
      semiconductor tapered amplifier.
AB  - The output of two grating-stabilized external-cavity diode lasers was injected
      into a semiconductor tapered amplif ier in a master oscillator-power amplif ier
      (MOPA) configuration. At a wavelength of 671 nm this configuration produced 210
      mW of power in a diffraction-limited mode with two frequency components of narrow
      linewidth. The frequency difference delta was varied from 20 MHz to 12 GHz, while
      the power ratio of the two components was freely adjustable. For delta < 2 GHz
      additional frequency sidebands appear in the output of the MOPA. This
      configuration is a f lexible and simple high-power cw laser source for light with
      multiple narrow-linewidth frequency components.

PMID- 18071438
TI  - 183-W, M(2) = 2.4 Yb:YAG Q-switched laser.
AB  - We have fabricated a diode-array end-pumped Yb:YAG rod laser with output powers
      greater than 200 W cw and 195 W Q -switched at 5 kHz. At an output power of 183 W
      and a repetition rate of 5 kHz, the beam quality was measured to be M(2)=2.4 .
      The laser design incorporates a hollow lens duct to concentrate the diode pump
      light for delivery to the end of the laser rod while maintaining access to the
      laser beam. This configuration provides increased flexibility for the resonator
      design and permits the use of birefringence compensation in the cavity to yield
      polarized output with increased efficiency. Using the recently described
      birefringence compensation method of Clarkson et al. [in Conference on Lasers and
      Electro-Optics (Optical Society of America, Washington, D.C., 1998), paper
      CTuI3], we obtained 112 W of cw power with a polarized beam of M(2)=3.2.

PMID- 18071439
TI  - Bit-error rate and frequency response in superregenerative semiconductor laser
      receivers.
AB  - A superregenerative receiver scheme developed for radio communications is
      translated to the scope of optical communications. Starting from application of
      the quasi-deterministic theory to the single-mode Langevin rate equations, closed
      expressions for basic parameters and features, such as bit-error rate and
      frequency response, are obtained. A comparison of superregenerative receivers
      with well-established optical receivers shows that improvements in direct
      detection receiver sensitivities of more than 10 dB can be obtained; this places
      superregenerative receiver sensitivities closer to the shot limit. Moreover, the
      intrinsic frequency selectivity of the superregenerative scheme makes it
      especially suitable for wavelength-division multiplexed systems. Finally,
      appropriate devices for implementation of this receiver are suggested.

PMID- 18071441
TI  - High-average-power, 1-MW peak-power self-mode-locked Ti:sapphire oscillator.
AB  - We describe a novel self-mode-locked Ti:sapphire ring laser that produces 13-fs
      pulses with peak powers exceeding 1 MW, pulse energies of 13 nJ, and average mode
      locked output powers of 1.5 W at a cavity repetition frequency of 110 MHz. A
      complete resonator analysis describing the optimum mode-locking configuration is
      presented, together with fringe-resolved autocorrelation and sonogram
      measurements of the output pulses.

PMID- 18071440
TI  - Petawatt laser pulses.
AB  - We have developed a hybrid Ti:sapphire-Nd:glass laser system that produces more
      than 1500 TW (1.5 PW) of peak power. The system produces 660 J of power in a
      compressed 440+/-20 fs pulse by use of 94-cm master diffraction gratings.
      Focusing to an irradiance of >7x10(20) W/cm (2) is achieved by use of a
      Cassegrainian focusing system employing a plasma mirror.

PMID- 18071442
TI  - Femtosecond Kerr-lens mode locking with negative nonlinear phase shifts.
AB  - We report a Kerr-lens mode-locked Cr:forsterite laser operated with negative
      nonlinear phase shift. The nonlinear phase shift is induced by the cascade
      chi((2;)):chi((2)) process in a lithium triborate crystal. Employing the cascade
      process at large phase mismatch produces a nearly linear frequency chirp.
      Transform-limited pulses as short as 60 fs are generated with positive cavity
      dispersion.

PMID- 18071443
TI  - Low-distortion hybrid optical shuffle concept.
AB  - A hybrid micro-macro-optical shuffle interconnection approach is described. The
      new concept minimizes distortion in multichip smart-pixel shuffle interconnection
      systems that use macro-optics to link dense arrays of vertical-cavity surface
      emitting laser (VCSEL) sources and matching arrays of detectors. The typical
      narrow-beam cones of VCSEL's are exploited by use of beam-deflecting micro-optics
      to create an optical system that is symmetric about its aperture. Since symmetric
      systems are well known to cancel distortion, this novel concept provides the
      means to achieve the required high degree of interchip registration accuracy.

PMID- 18071445
TI  - Phase imaging with partially coherent x rays.

PMID- 18071444
TI  - Optical coherent transient continuously programmed continuous processor.
AB  - A novel technique for continuously programming an optical coherent transient
      spatial-spectral signal processor is proposed. The repeated application of two
      spatially distinct optical programming pulses to a nonpersistent hole-burning
      material writes an accumulated spatial-spectral population grating. An optical
      data stream is introduced on a third beam, resulting in a processor output signal
      that is spatially distinct from all the input pulses. Programming and processing
      take place simultaneously, asynchronously, and continuously. In the case of true
      time delays, the efficiency that is achievable with currently available materials
      is of the order of that predicted for a perfect photon-gated device.

PMID- 18071447
TI  - Ultrasonic tagging of photon paths in scattering media: parallel speckle
      modulation processing.
AB  - Tagging of photon trajectories in scattering media is possible by application of
      a localized ultrasonic field to the sample and by measurement of the induced
      speckle modulation. Instead of using a single optical detector, which integrates
      the signal of many speckle grains, we propose a more efficient detection scheme
      that uses a CCD camera and parallel lock-in detection to record the full
      modulation of the speckle. The advantage of this multiplex detection is
      demonstrated, as well as the imaging capabilities of the process for biological
      tissues.

PMID- 18071446
TI  - Photoacoustic spectroscopy using quantum-cascade lasers.
AB  - Photoacoustic spectra of ammonia and water vapor were recorded by use of a
      continuous-wave quantum-cascade distributed-feedback (QC-DFB) laser at 8.5 mum
      with a 16-mW power output. The gases were flowed through a cell that was resonant
      at 1.6 kHz, and the QC-DFB source was temperature tuned over 35 nm for generation
      of spectra or was temperature stabilized on an absorption feature peak to permit
      real-time concentration measurements. A detection limit of 100 parts in 10(9) by
      volume ammonia at standard temperature and pressure was obtained for a 1-Hz
      bandwidth in a measurement time of 10 min.

PMID- 18071448
TI  - Bistable nonspecular reflection at a nonlinear-linear local interface: errata.

PMID- 18071449
TI  - Polarization effects in apertureless scanning near-field optical microscopy: an
      experimental study.
AB  - Strong electric-field enhancements at the apex of a tungsten tip illuminated by
      an external light source were recently predicted theoretically. We present an
      experimental study of the dependence of this effect on the polarization angle of
      the incident light. It is shown that the intensity of the light scattered by the
      tungsten tip of an apertureless scanning near-field optical microscope is 2
      orders of magnitude higher when the incident light is p polarized than when it is
      s polarized. This experimental result is in good agreement with theoretical
      predictions and provides an easy way to test the quality of the tips.

PMID- 18071450
TI  - Rapid and robust detection of branch points from wave-front gradients.
AB  - We discuss a technique that permits branch points in the phase function to be
      localized in real-time adaptive-optics systems and that is unambiguous and robust
      in the presence of noise.

PMID- 18071451
TI  - Noncritically phase-matched frequency conversion in Gd(x)Y(1-x)Ca(4)O(BO(3))(3)
      crystal.
AB  - A nonlinear optical crystal YCa(4)O(BO(3))(3) (YCOB) is phase matchable for third
      harmonic generation (THG) of a Nd:YAG laser by type I mixing between 1.064 and
      0.532mum . By partial substitution of Gd for Y in YCOB, a solid solution Gd(x)Y(1
      x)Ca(4)O(BO(3))(3) gradually changes the phase-matching angles of THG to (theta,
      o)=(90( degrees ), 90 ( degrees )) . We present the properties of noncritically
      phase-matched THG in Gd(x) Y(1-x)Ca(4)O(BO(3))(3) (x=0.28) .

PMID- 18071452
TI  - Cascaded contributions to degenerate four-wave mixing in an acentric organic
      crystal.
AB  - We show both theoretically and experimentally by degenerate four-wave mixing that
      the combined processes of optical rectification and the linear electro-optic
      effect contribute to the large effective third-order susceptibilities
      [14chi((3))(CS(2))] of the organic salt 4-N, N^- dimethylamino-4(?) -N(?) 
      methylstilbazolium toluene-p- sulfonate (DAST). Furthermore, the knowledge of the
      cascaded contributions was used to determine absolute values of the third-order
      susceptibilities as well as their sign.

PMID- 18071453
TI  - High-resolution, high-speed photorefractive incoherent-to-coherent optical
      converter.
AB  - We demonstrate a photorefractive incoherent-to-coherent optical converter driven
      by ultraviolet light that provides a 35-mus response time and an optical
      resolution of 124 line pairs/mm. The device, implemented in KNbO(3) , operates
      with a modulating intensity of 85 mW/cm(2) , which corresponds to an optical
      switching energy per bit of 0.5 pJ. A conversion rate of the order of 90 Gbits/(s
      cm(2)) is achieved. The conversion between the ultraviolet light and the visible
      laser beam at lambda=532 nm occurs through anisotropic Bragg diffraction at a
      modulated interband photorefractive grating. Our device has a better optical
      resolution and conversion rate than optically addressed solid-state spatial light
      modulators based on the photorefractive effect and multiple quantum wells, and it
      is also faster than devices based on liquid crystals.

PMID- 18071454
TI  - Enhancement of terahertz-wave output from LiNbO(3) optical parametric oscillators
      by cryogenic cooling.
AB  - In recent years widely tunable terahertz- (THz-) wave generation from LiNbO(3)
      optical parametric oscillators (OPO's) has been successfully demonstrated by use
      of the prism output-coupler method. However, there remains a problem of large
      absorption loss for generated terahertz waves inside the crystal, so we
      investigated the cryogenic characteristics of the OPO. We achieved 125-times
      higher THz-wave output and 32% reduction of the generation threshold by cooling
      the crystal to 78 K. This scheme also provides direct loss measurement at THz
      frequency, and we found that the THz-wave enhancement mechanism is improvement of
      the gain as well as the reduction of the absorption coefficient.

PMID- 18071455
TI  - Generation of 740 mW of blue light by intracavity frequency doubling with a first
      order quasi-phase-matched KTiOPO(4) crystal.
AB  - We report on efficient intracavity frequency doubling of a cw diode-pumped Nd:YAG
      laser on the (4)F(3/2)?(4)I(9/2) laser transition at 946 nm. The nonlinear
      crystal used in the experiments was a first-order quasi-phase-matched flux-grown
      KTiOPO(4) crystal (period, 6.09mum ; thickness, 1 mm; length, 9 mm). The
      fluctuations in the generated second-harmonic wave were lower than 3% at output
      powers of as much as 500 mW. The overall optical-to-optical efficiency was 5.7%.
      A maximum output power of 740 mW of blue light was generated, which was stable
      for only 0.5 min. The decrease the output power at this power level was
      attributed to heating and thermal lensing in the periodically poled KTiOPO(4)
      crystal. The short-term behavior of the second-harmonic wave exhibited switching
      between a cw mode and chaotic intensity fluctuations.

PMID- 18071456
TI  - Greater than 20%-efficient frequency doubling of 1532-nm nanosecond pulses in
      quasi-phase-matched germanosilicate optical fibers.
AB  - We fabricated second-order nonlinear gratings in D-shaped germanosilicate fibers,
      using thermal poling and periodic electrodes defined by standard
      photolithography. These gratings, which are up to 75 mm long, were used for
      efficient quasi-phase-matched frequency doubling of 1.532-mum nanosecond pulses
      from a high-power erbium-doped fiber amplifier. Average second-harmonic powers as
      high as 6.8 mW and peak powers greater than 1.2 kW at 766 nm were generated, with
      average and peak conversion efficiencies as high as 21% and 30%, respectively.

PMID- 18071457
TI  - Diffraction of light from phase gratings at large modulation depths: transient
      grating experiments in liquids at high laser powers.
AB  - Generation of transient gratings in weakly absorbing liquids with a high-power
      laser gives rise to changes in the fluid's index of refraction that are
      sufficiently large to produce both multiple diffraction of a probe laser beam and
      a time response anomaly. The coupled-wave approach to the solution of the volume
      diffraction problem is shown to predict the existence of high-order diffraction
      of the probe beam and the time dependence of the diffraction intensity of each
      order. In addition, criteria for the Raman-Nath and Bragg diffraction regimes are
      derived from the first-order, coupled-wave equations.

PMID- 18071458
TI  - Accuracy of optical frequency comb generation in optical fiber.
AB  - We evaluated the accuracy of an optical frequency comb in optical fibers by
      measuring the frequency shift after a sideband from an electro-optic modulator
      had passed through the fiber. We found that a frequency drift of a few hertz was
      due largely to a variation in the ambient temperature that corresponded to an
      increase in the square root of the Allan variance to 0.66 Hz.

PMID- 18071459
TI  - Collisions in dispersion-managed soliton propagation.
AB  - We study collisions in dispersion-managed soliton propagation for wavelength
      division multiplexing application at zero net dispersion when the Gordon-Haus
      timing jitter is removed. We show that the collisions can lead to group-velocity
      changes and spectral collapse. Large channel separation ameliorates the effects.
      Filters prevent spectral collapse but do not affect the velocity changes.

PMID- 18071460
TI  - Effect of guiding filters on the behavior of dispersion-managed solitons.
AB  - We show that guiding filters fundamentally alter the behavior of dispersion
      managed soltions by making the pulse energy nearly independent of path-average
      dispersion (D?) in the neighborhood of D?=0 . This fact enables one to design
      maps permitting adequate pulse energy with narrow-bandwidth, temporally broad
      pulses for the attainment of high spectral efficiency and reduced nonlinear
      penalties in wavelength-division multiplexing.

PMID- 18071461
TI  - Scheme for the characterization of dispersion-managed solitons.
AB  - We give a simple new derivation of the ordinary differential equations that
      describe approximately the behavior of dispersion-managed solitons, and a new
      scheme for their solution in which the nonlinear dispersive and spectral effects
      are clearly apparent.

PMID- 18071462
TI  - Uniform transverse-electric fundamental wave in a symmetric linear multilayer
      optical waveguide.
AB  - In the context of a symmetric linear multilayer optical waveguide, a special
      transverse-electric fundamental (TE(0)) wave is analyzed that has identical
      amplitudes in the guide core. The guided structural parameters, such as the core
      thickness, the number of wells, and the ratio of the well thickness to the
      periodic length, must have specific relationships to one another to form this
      kind of uniform TE(0) wave. These relationships are investigated, and some field
      profiles of the uniform TE(0) wave are plotted.

PMID- 18071463
TI  - Self-mode-locked pulsed monomode laser.
AB  - We predict the existence of a new pulsed-laser operation regime, when the phases
      and polarizations of the two coupled cold-cavity eigenstates of a monomode solid
      state laser are taken into account in the derivation of the Maxwell-Bloch
      equations. This monomode pulsed regime is experimentally observed, without any
      normal mode locking or Q switching occurring inside the cavity. We obtain close
      agreement between experiments and theory, even in the simple case of a Nd:YAG
      microchip laser, for which sech(2) pulses at nearly megahertz repetition rates
      are readily observed.

PMID- 18071464
TI  - 530-mW 7-kHz cerium LiCAF laser pumped by the sum-frequency-mixed output of a
      copper-vapor laser.
AB  - We report, for what we believe to be the first time, a Ce:LiCAF laser pumped by
      ultraviolet radiation obtained by sum-frequency mixing of the green and the
      yellow output from a copper-vapor laser. The 7-kHz pulse repetition frequency
      free-lasing Ce:LiCAF laser yielded a maximum output power of 530 mW, with a slope
      efficiency of 32%, from a pump power of 1.9 W. With a single prism tunability
      from 280.5 to 316 nm was achieved.

PMID- 18071465
TI  - Two-element dielectric antenna serially excited by optical wavelength
      multiplexing.
AB  - A single pulsed laser beam containing multiple wavelengths (wavelength
      multiplexing) is employed to activate two semiconductor antennas in series. The
      dielectric nature of the semiconductors permits serial cascading of the antenna
      elements. Recently observed nonlinear characteristics of the radiated field as a
      function of the free carrier accelerating (bias) voltage are used to minimize the
      small interactions between elements. We demonstrate that the temporal
      electromagnetic radiation distribution of two serial antennas is sensitive to the
      three-dimensional pattern of the optical excitation source. One can, in turn,
      vary this distribution continuously by optical means to reconfigure the array.

PMID- 18071466
TI  - Demonstration of phase correlation in multiwavelength mode-locked semiconductor
      diode lasers.
AB  - Wideband spectral phase correlation is demonstrated from a multiwavelength mode
      locked semiconductor laser. By use of frequency-resolved optical gating
      techniques, significant phase correlation was observed between multiple
      intracavity oscillating wavelengths, with wavelength separations of ~1 nm . The
      resultant temporal characteristics show a substantial modulation owing to the
      spectral coupling induced by intracavity-generated four-wave mixing. This result
      may lead to novel methods for directly generating ultrafast subpicosecond optical
      pulse sequences with spectrally tailored amplitude and phase characteristics from
      actively mode-locked semiconductor lasers.

PMID- 18071467
TI  - Generation and characterization of terahertz pulse trains from biased, large
      aperture photoconductors.
AB  - The saturation properties of terahertz emission from biased, large-aperture
      photoconductors excited by trains of amplified femtosecond optical pulses are
      presented. A direct comparison is made of the multiple-pulse saturation
      properties of terahertz emission from semi-insulating GaAs and low-temperature
      grown GaAs emitters with different carrier lifetimes. When the carrier lifetime
      is less than or comparable with the interpulse spacing, a significant enhancement
      of the narrow-band terahertz output is observed. The enhancement is not observed
      for emitters with long carrier lifetimes, consistent with the results of a
      previously derived saturation theory [Opt. Lett. 18, 1340 (1993)].

PMID- 18071468
TI  - Probing microscopic chemical environments with high-intensity chirped pulses.
AB  - By varying the chirp of high-intensity pulses, we can use the chirp-condition
      dependent fluorescence yield to distinguish among different molecules or the same
      molecule in different microenvironments. As an example of the latter we show that
      SNAFL-2, a well-known pH-sensitive dye, shows large modulation in fluorescence
      yield in response to both variation in acidity and variation in chirp condition.
      Future application of this technique as a novel contrast mechanism within
      fluorescence microscopy is discussed.

PMID- 18071469
TI  - Amplitude and chirp characterization of high-power laser pulses in the 5-fs
      regime.
AB  - Frequency-resolved optical gating (FROG) based on second-harmonic generation has
      been demonstrated to be capable of high-fidelity measurement of the electric
      field envelope and of the temporal evolution of the instantaneous carrier
      frequency of 0.1-TW 5-fs pulses without the need for any correction for
      systematic experimental errors. At a 1-kHz repetition rate, pulse energies of a
      few microjoules are sufficient for reliable FROG characterization of pulses with
      durations down to the single-cycle regime. The results obtained reveal that
      carefully designed hollow-fiber chirped-mirror compressors are able to deliver
      high-power sub-10-fs pulses with a smooth Gaussianlike leading edge that has an
      intensity contrast of approximately 10(-2) .

PMID- 18071470
TI  - Modulating and scanning the mode-lock frequency of an 800-MHz femtosecond
      Ti:sapphire laser.
AB  - An 800-MHz self-mode-locked femtosecond Ti:sapphire laser has been developed
      whose mode-lock frequency can be robustly scanned and modulated. The laser is
      based on the three-element design of Ramaswamy-Paye and Fujimoto [Opt. Lett. 19,
      1756 (1994)]. By translation and modulation of the position of the prismatic
      output coupler, the mode-lock frequency can be reliably scanned more than 1% and
      modulated at 80 Hz with a deviation of 2.5 kHz without interrupting the mode
      lock, changing the pulse length, or inducing significant amplitude modulation. An
      application in tunable high-resolution terahertz spectroscopy is also
      demonstrated.

PMID- 18071471
TI  - Three-dimensional tomography using a cubic-phase plate extended depth-of-field
      system.
AB  - We use cubic-phase plate imaging to demonstrate an order-of-magnitude improvement
      in the transverse resolution of three-dimensional objects reconstructed by
      extended depth-of-field tomography. Our algorithm compensates for the range shear
      of the cubic-phase approach and uses camera rotation to center the reconstructed
      volume on a target object point.

PMID- 18071472
TI  - Control of optical transmission through metals perforated with subwavelength hole
      arrays.
AB  - The transmission spectrum of a metal that is perforated with a periodic array of
      subwavelength holes exhibits well-defined maxima and minima resulting from,
      respectively, a transmission enhancement by surface plasmons and Wood's anomaly,
      a diffraction effect. These features occur at wavelengths determined by the
      geometry of the hole arrays, the refractive index of the adjacent medium, and the
      angle of incidence. We demonstrate control of the transmission through variation
      of these parameters and show that perforated metal films may form a novel basis
      for electro-optic devices such as flat-panel displays, spatial light modulators,
      and tunable optical filters.

PMID- 18071473
TI  - Suppression of classic and quantum radiation pressure noise by electro-optic
      feedback.
AB  - We present theoretical results that demonstrate a new technique that can be used
      to improve the sensitivity of thermal noise measurements: intracavity intensity
      stabilization. It is demonstrated that electro-optic feedback can be used to
      reduce intracavity intensity fluctuations, and the consequent radiation pressure
      fluctuations, by a factor of 2 below the quantum-noise limit. We show that this
      reduction is achievable in the presence of large classic intensity fluctuations
      in the incident laser beam. The benefits of this scheme are a consequence of the
      sub-Poissonian intensity statistics of the field inside a feedback loop and the
      quantum nondemolition nature of radiation pressure noise as a readout system for
      the intracavity intensity fluctuations.

PMID- 18071474
TI  - Observations of non-Rayleigh statistics in the approach to photon localization.
AB  - We measure the distribution of intensity of microwave radiation transmitted
      through absorbing random waveguides of lengths L up to localization length xi .
      For large intensity values the distribution is given by a negative stretched
      exponential to the 1/2 power, in agreement with predictions by Nieuwenhuizen and
      van Rossum [Phys. Rev. Lett. 74, 2674 (1995)] for diffusing waves in nonabsorbing
      samples, as opposed to a negative exponential given by Rayleigh statistics. The
      intensity distribution is well described by a transform derived by Kogan and
      Kaveh [Phys. Rev. B 52, R3813 (1995)] of the measured distribution of total
      transmission.

PMID- 18071475
TI  - Multilayer volume holographic optical memory.
AB  - We demonstrate a scheme for volume holographic storage based on the features of
      shift selectivity of a speckle reference-wave hologram. The proposed recording
      method permits more-efficient use of the recording medium and yields greater
      storage density than spherical or plane-wave reference beams. Experimental
      results of multiple hologram storage and replay in a photorefractive crystal of
      iron-doped lithium niobate are presented. The mechanisms of lateral and
      longitudinal shift selectivity are described theoretically and shown to agree
      with experimental measurements.

PMID- 18071476
TI  - Microscopic fluorescence imaging of bulk defect clusters in KH(2)PO(4) crystals.
AB  - A microscopic fluorescence imaging system is used to detect optically active
      centers located inside a transparent dielectric crystal. Defect centers in the
      bulk of KH(2)PO(4) crystals are imaged based on their near-infrared emission
      following photoexcitation. The spatial resolution of the system is 1mum in the
      image plane and 25mum in depth. The experimental results indicate the presence of
      a large number of optically active defect clusters in different KH(2)PO(4)
      crystals, whereas the concentration of these clusters depends on the crystal
      sector and growth method.

PMID- 18071477
TI  - Field stitching algorithm for the analysis of electrically large diffractive
      optical elements.
AB  - A rigorous electromagnetic algorithm is presented for the analysis of
      electrically large diffractive optical elements (DOE's), i.e., those that contain
      small features and have large apertures compared with the wavelength of
      illumination. The technique uses a finite-sized analysis window within which a
      rigorous electromagnetic technique is used to solve the local boundary-value
      problem. To this end the boundary-element and finite-difference time-domain
      methods are used. The analysis window is translated over the entire surface of
      the DOE and stitches together the complete solution. We validate the techniques
      by comparing the stitched boundary fields with those of a complete analysis, in
      both magnitude and phase, for a binary lens. To illustrate the utility of our
      method we analyzed an eight-level diffractive lens with a 10, 000-wavelength
      diameter sampled at 0.05 wavelength that required 8 Mbytes of memory on a desktop
      personal computer.

PMID- 18071478
TI  - Full-vector analysis of a realistic photonic crystal fiber.
AB  - We analyze the guiding problem in a realistic photonic crystal fiber, using a
      novel full-vector modal technique. This is a biorthogonal modal method based on
      the non-self-adjoint character of the electromagnetic propagation in a fiber.
      Dispersion curves of guided modes for different fiber structural paremeters are
      calculated, along with the two-dimensional transverse intensity distribution of
      the fundamental mode. Our results match those achieved in recent experiments in
      which the feasibility of this type of fiber was shown.

PMID- 18071479
TI  - Passive erbium-doped fiber seed photon generator for high-power Er(3+)-doped
      fiber fluorescent sources with an 80-nm bandwidth.
AB  - A novel structure that converts wasted backward amplified spontaneous emission
      (ASE) to seed photons for the amplifier stage is suggested for a high-power
      erbium-doped fiber (EDF) broadband source. A considerable increase in output
      power and bandwidth extension was achieved by placement of a segment of passive
      EDF in front of the amplifier stage, thus recycling backward ASE as the secondary
      pumping source for the passive EDF seed photon generator. Experimental results
      showed a dramatic increase in output ASE power of more than 10 dB for most
      radiation bands from 1540 to 1620 nm with the simple addition of an unpumped EDF
      segment to the ordinary fluorescence-source structure.

PMID- 18071480
TI  - Digitally controlled fault-tolerant multiwavelength programmable fiber-optic
      attenuator using a two-dimensional digital micromirror device.
AB  - A digitally controlled multiwavelength variable fiber-optic attenuator using a
      two-dimensional digital micromirror device (DMD) is introduced. The results from
      an experimental four-wavelength (i.e., 1546.92, 1548.52, 1550.12, and 1551.72 nm)
      proof-of-concept attenuator indicate a 26-dB dynamic range and 11-bit resolution.
      The measured attenuator average coherent optical cross talk per wavelength
      channel is -38 dB , limited by the additive noise resulting from the nonideal
      isolation of the optical circulator and the attenuator module. The average
      optical loss for our experimental attenuator is 15 dB and is limited mainly by
      the visible-mode DMD that is used as a 1550-nm infrared window device. Our
      theoretical estimate of a <8-dB loss optimized attenuator can be used for
      equalization in multiwavelength fiber-optic communications with as many as 108
      wavelengths.

PMID- 18071481
TI  - Dispersion-managed solitons for terrestrial transmission.
AB  - We describe a scheme involving the insertion of segments of dispersion
      compensating fiber, pumped to yield Raman gain, at one or more intermediate
      points within each 80-km-or-greater span between amplifier huts. With dispersion
      managed solitons, the scheme is expected to allow for error-free, many-channel
      wavelength-division multiplexing, with high spectral efficiency, over
      transmission distances of many thousands of kilometers.

PMID- 18071482
TI  - Use of continuous-wave illumination for two-photon three-dimensional optical bit
      data storage in a photobleaching polymer.
AB  - We show that a continuous-wave laser beam at an infrared wavelength of 800 nm can
      be used for two-photon three-dimensional bit data storage in a photobleaching
      polymer. We successfully demonstrate recording and reading of six layers of data
      bits with a transverse bit separation of 4.3microm and an axial layer separation
      of 20microm . This result leads to a three-dimensional bit density of
      approximately 3Gbits/cm(3) .

PMID- 18071483
TI  - Digital holography for quantitative phase-contrast imaging.
AB  - We present a new application of digital holography for phase-contrast imaging and
      optical metrology. This holographic imaging technique uses a CCD camera for
      recording of a digital Fresnel off-axis hologram and a numerical method for
      hologram reconstruction. The method simultaneously provides an amplitude-contrast
      image and a quantitative phase-contrast image. An application to surface
      profilometry is presented and shows excellent agreement with contact-stylus probe
      measurements.

PMID- 18071484
TI  - Phase-shifting polarization interferometry for microstructure linewidth
      measurement.
AB  - We report on a novel procedure to measure the linewidth of steep microstructures,
      based on the polarization anisotropy caused by the structure edges. A liquid
      crystal phase shifter and a polarizer are introduced into the imaging optics of a
      reflection-mode microscope. We apply the principle of phase-shifting
      interferometry to measure the phase and contrast of a TM-polarized image with the
      TE-polarized image as reference. The method provides selective edge detection
      because the polarization difference is localized at the structure edges.

PMID- 18071485
TI  - Surface-profile measurement by means of a polarization Sagnac interferometer with
      parallel optical feedback.
AB  - We describe a novel feedback interferometer for real-time, unambiguous
      measurement of surface profiles that consists of a polarization Sagnac
      interferometer and an optically addressed phase-only spatial light modulator. In
      this system the output intensity from the Sagnac interferometer is optically fed
      back to the phase modulator placed in one arm of the interferometer, which
      produces a sawtooth fringe intensity profile (instead of the conventional
      cosinusoidal one) that is directly and unambiguously related to the surface
      profile. Preliminary experimental results demonstrate the feasibility of applying
      this system to surface-profile measurement.

PMID- 18071486
TI  - Determination of the depth-resolved Stokes parameters of light backscattered from
      turbid media by use of polarization-sensitive optical coherence tomography.
AB  - Polarization-sensitive optical coherence tomography (PS-OCT) was used to
      characterize completely the polarization state of light backscattered from turbid
      media. Using a low-coherence light source, one can determine the Stokes
      parameters of backscattered light as a function of optical path in turbid media.
      To demonstrate the application of this technique we determined the birefringence
      and the optical axis in fibrous tissue (rodent muscle) and in vivo rodent skin.
      PS-OCT has potentially useful applications in biomedical optics by imaging
      simultaneously the structural properties of turbid biological materials and their
      effects on the polarization state of backscattered light. This method may also
      find applications in material science for investigation of polarization
      properties (e.g., birefringence) in opaque media such as ceramics and crystals.

PMID- 18071487
TI  - Fourier synthesis of 9.6-GHz optical-pulse trains by phase locking of three
      continuous-wave semiconductor lasers.
AB  - Fourier synthesis of optical-pulse trains based on optical phase locking of three
      cw semiconductor lasers has been demonstrated by use of a semiconductor optical
      amplifier as a four-wave mixer. The temporal waveforms of the pulse trains were
      directly observed at a repetition rate of 9.6 GHz by a fast sampling
      oscilloscope. The FM sideband heterodyne technique was employed to realize a
      stable homodyne optical phase-locked loop.

PMID- 18071488
TI  - Amplifying volume in scattering media.
AB  - We investigate the influence of the excitation spot diameter on the laser
      threshold of a scattering amplifying medium. Fluorescence spectra are recorded
      from a suspension of TiO(2) scatterers in Sulforhodamine B dye. The threshold
      pump intensity becomes larger by a factor of 70 if the excitation beam diameter
      gets close to the mean free path?. This increase is explained by use of a simple
      model describing diffusion out of the amplifying volume and is confirmed by a
      Monte Carlo simulation.

PMID- 18071489
TI  - Real-time reflectivity and topography imagery of depth-resolved microscopic
      surfaces.
AB  - We have constructed an interference microscope that produces, in real time,
      reflectivity and topography images of surfaces with depth discrimination better
      than 1>mu;m . Intensity and phase images are obtained at the rate of 50 per
      second by use of a multiplexed lock-in detection and MMX assembler-optimized
      calculation routines. With a wavelength of 0.84microm , depth discrimination of
      0.7microm and lateral resolution of 0.3microm were demonstrated, in good
      agreement with theory. Two-dimensional cross-sectional reflectivity and
      topography images taken at different depths in an integrated circuit are
      presented.

PMID- 18071490
TI  - Recording of second-harmonic index gratings in photorefractive (K(0.5)
      Na(0.5))(0.2) (Sr(0.75) Ba(0.25))(0.9) Nb(2)O(6) crystals.
AB  - We propose and demonstrate a novel method for recording second-harmonic volume
      index gratings in photorefractive crystals. The fundamental component of the
      index grating is eliminated by means of a pi -phase shifted double-exposure
      process that uses the Mach-Zehnder interferometric technique. Experimental
      results for (K(0.5) Na(0.5)) (0.2)(Sr> (0.75)Ba (0.25))(0.9)Nb (2)O(6) crystals
      are presented and discussed.

PMID- 18071491
TI  - Second-harmonic generation of an optical frequency comb at 1.55 microm with
      periodically poled lithium niobate.
AB  - To expand the span of the optical frequency comb (OFC), we generated the second
      harmonics of an OFC at 1.55microm , using a multiperiod periodically poled
      lithium niobate (PPLN) crystal. A coupled-cavity OFC generator with an average
      output power of 0.2 mW was amplified and expanded with a fiber amplifier and a
      dispersion-flattened fiber. The fundamental OFC average power and span were 100
      mW and 45 THz, respectively. The second-harmonic comb's span was 3.2 THz;
      however, we tuned the center frequency over 30 THz by changing the poling period.
      We also demonstrated that the second-harmonic comb can be used for frequency
      difference measurement.

PMID- 18071492
TI  - Random evolution and coherence degradation of a high-order optical soliton train
      in the presence of noise.
AB  - The intrinsic evolution of a high-order soliton described by the nonlinear
      Schrodinger equation is initiated by a self-four-wave mixing effect (or
      modulational instability) and recurs neatly every soliton period. We show that
      when there is noise such as amplified spontaneous emission, however, a high-order
      soliton evolves randomly and independently and is distorted because the evolution
      is initiated by noise. Thus the time and the frequency coherence of a soliton
      pulse train are both greatly degraded.

PMID- 18071493
TI  - Resonant photorefractive effect in InGaAs/GaAs multiple quantum wells.
AB  - Semi-insulating InGaAs/GaAs multiple quantum wells are fabricated by metal
      organic vapor-phase epitaxy and proton implantation. Two-wave mixing gain and
      four-wave mixing diffraction efficiency are measured at wavelengths of 0.91
      0.94microm in the Franz-Keldysh geometry. We observe a large photorefractive
      effect caused by the excitonic electro-optic effect. The maximum diffraction
      efficiency reaches ~1.5x10(-4) .

PMID- 18071494
TI  - Programmable high-bit-rate pattern generator with a segmented semiconductor
      optical amplifier.
AB  - We have demonstrated that spatial gain modulation in a segmented semiconductor
      optical amplifier can be converted to a temporal signal. A four-segment amplifier
      was used to generate digital return-to-zero patterns at 40 Gbits/s , and this
      technique should be readily scalable to more than 100 Gbits/s .

PMID- 18071495
TI  - Interaction between vector solitons and solitonic gluons.
AB  - We describe a physical mechanism for creating multisoliton bound states by which
      optical solitons are glued together by attraction between the nonsoliton beams
      that they guide, solitonic gluons. We verify the concept of the solitonic gluons
      experimentally, observing a suppression of the repulsion between dark solitons
      owing to an attractive force acting between out-of-phase bright guided beams.

PMID- 18071496
TI  - Nanosecond optical parametric oscillator based on large-aperture periodically
      poled RbTiOAsO(4).
AB  - We report on optical parametric oscillators (OPO's) based on periodically poled
      RbTiOAsO(4) (PP RTA), which are pumped by Q -switched solid-state lasers. With a
      diode-pumped Nd:YVO(4) laser (pulse energy, 800microJ ; pulse duration, 5.5 ns;
      repetition rate, 1 kHz) the PP RTA OPO generated 1.58-microm signal and 3.26
      microm idler radiation with a signal pulse energy of 45microJ . The large
      aperture of 3 mmx3 mm of the PP RTA crystal also permitted OPO operation with
      pump pulse energies as high as 65 mJ, provided by a flash-lamp-pumped Q -switched
      Nd:YAG laser (pulse duration, 20 ns; repetition rate, 10 Hz). With this pump
      source the OPO generated signal pulse energies as high as 17 mJ, corresponding to
      an efficiency of 26%. The performance of this OPO shows that large-aperture PP
      RTA crystals are well suited for pulsed nanosecond OPO operation with pump pulse
      energies of tens of millijoules.

PMID- 18071497
TI  - Wave-front control and aberration correction with a diffractive optical element.
AB  - A method that permits aberration correction and wave-front reshaping with a
      diffractive optical element (DOE) is described. Two aligned DOE's made of two
      different dispersive materials are used. The different dispersions of the two
      materials in addition to freedom in choosing their thicknesses enables the
      chromatic aberration and the wave fronts to be manipulated. Design and simulation
      of such DOE's are described.

PMID- 18071498
TI  - Analysis of fringe locking in a laser diode interferometer under injection
      current modulation.
AB  - A theoretical analysis has been performed that explains a fringe-locking
      phenomenon observed in a two-beam interferometer in which a laser diode was
      subjected to optical feedback and modulation of its injection current. The
      dependence of wavelength change on the injection-current variation is calculated
      by use of a model of coupled resonators consisting of the laser cavity and the
      interferometer. The fringe phase change caused by modulation of the injection
      current is derived from this model and has proved to be suppressed within much
      less than 2pi in excess of an integer multiple of 2pi if the path difference of
      the interferometer is longer than 10 mm. The calculated phase fluctuation agrees
      well with those observed in experiments.

PMID- 18071499
TI  - Sky implementation of modal predictive control in adaptive optics.
AB  - We present what we believe are the first experimental results obtained with modal
      linear predictive control of an adaptive optics system operating on sky at a
      visible wavelength on a 1.52-m telescope (Observatoire de Haute-Provence,
      France). This system yields substantially better results than optimized integral
      control: a 30% relative gain in Strehl ratio is measured, even in conditions of
      low wind speed.

PMID- 18071500
TI  - Enhanced responsivity of non-steady-state photoinduced electromotive force
      sensors using asymmetric interdigitated contacts.
AB  - The responsivity at a constant detection area of non-steady-state photoinduced
      electromotive force (photo-emf) detectors is improved by a factor equal to the
      number of contact pairs contained in asymmetric interdigitated surface contacts.
      The polar nature of photo-emf current generation requires contact asymmetry in
      which one increases the total signal by blocking the illumination between
      alternate contact pairs, in distinct contrast to the behavior of conventional
      interdigitated contacts fabricated upon isotropic photoconductors.

PMID- 18071501
TI  - Theory of microcavity-enhanced Raman gain.
AB  - We present a method for obtaining a simple relation between bulk and cavity
      modified Raman gains for microcavities with arbitrary geometric shapes. The
      analytical expression for the microcavity-enhanced Raman gain quantitatively
      accounts quite well for all the main features of the related experiments.

PMID- 18071502
TI  - All-optical quantum teleportation.
AB  - We propose an all-optical continuous-variable quantum teleportation scheme based
      on optical parametric amplifiers.

PMID- 18071503
TI  - Gas filter correlation instrument for air monitoring at submillimeter
      wavelengths.
AB  - A gas filter correlation (GFC) instrument for air monitoring at submillimeter
      wavelengths has been developed. We used a high-power terahertz radiation source
      in combination with a specific gas filter cell to obtain a highly selective
      instrument to differentiate species present in an unknown mixture. This approach
      provides a new method for survey measurements in the spectrum from 100 to 1000
      GHz, in which many molecular rotational lines appear. Basic operational
      considerations and preliminary experiments with hydrogen sulfide are described.

PMID- 18071505
TI  - Influence of Raman effects in wavelength-division multiplexed soliton systems:
      errata.

PMID- 18071504
TI  - Ultrashort, intense ultraviolet pulse generation by efficient frequency tripling
      and adapted phase matching.
AB  - We demonstrate efficient frequency tripling of 1057-chirped pulses, using adapted
      chirping and thick KDP crystals. These millijoules broadband pulses at 352 nm
      have been compressed to 220-fs duration by use of a UV grating-pair compressor.
      The technique is scalable to kilojoule petatwatt lasers.

PMID- 18071506
TI  - Synthesis of spatial coherence.
AB  - The mutual intensity function plays a major role in characterizing quasi
      monochromatic, partially coherent optical signals. We propose to use the mutual
      intensity as a carrier of information to avoid speckle noise in coherent
      illumination systems and to permit the use of complex functions that are
      prohibited spatially incoherent sources. To do this we require methods for
      encoding the information as a coherence function. An optical system for
      synthesizing a beam with a given mutual intensity function is proposed. The
      optical system permits the synthesis of any desired mutual intensity function.
      The illumination is supplied by a quasi-monochromatic, spatially incoherent
      source. Experimental results demonstrate the performance of this system for
      several cases.

PMID- 18071507
TI  - Reconstruction of the surface power spectrum from reflectivity data.
AB  - An analytical approach is used to determine the power spectrum of the surface
      roughness from experimental data for the reflectivity of randomly rough surfaces.
      A one-dimensional, randomly rough, perfectly conducting surface that is
      illuminated by s-polarized light whose plane of incidence is perpendicular to the
      generators of the surface is considered, and the power spectrum is obtained
      within the framework of phase perturbation theory. Good agreement with
      numerically generated experimental data is obtained.

PMID- 18071508
TI  - Storage and retrieval of correlation functions of partially coherent fields.
AB  - A new method is described for determining the two-point equal-time coherence
      function (the mutual intensity) and the two-point equal-time intensity
      correlation function of partially coherent fields. The method is reminiscent of
      conventional holography but differs from it in several important respects.

PMID- 18071509
TI  - Polarization-induced pulse spreading in birefringent optical fibers with zero
      differential group delay.
AB  - The polarization properties of concatenations of trunks of birefringent fibers
      and elements with polarization-dependent losses are analyzed. We show both
      theoretically and experimentally that the concatenation can have zero
      differential group delay over a whole range of wavelengths but that a pulse
      propagating down the concatenation can still experience significant pulse
      spreading. In this example the two main methods used for characterizing
      polarization mode dispersion in optical fiber systems, i.e., Jones matrix
      eigenanalysis and the interferometric method, give different results. This
      counterintuitive example underlines the need for a careful assessment of the
      basic concepts related to polarization effects in the presence of polarization
      dependent losses.

PMID- 18071510
TI  - Bistable solitons in inhomogeneously doubly doped fibers.
AB  - Bistable soliton (for which the nonlinear propagation constant shift is a double
      valued function of energy) solutions to the pulse evolution equation for a doubly
      but inhomogeneously doped (with one of the dopants) fiber are obtained
      numerically. Their physical characteristics are obtained and studied. It is shown
      that the theoretical prediction can be experimentally verified by a pair of
      dopants from an already available lot of dopants.

PMID- 18071511
TI  - Vector soliton fiber lasers.
AB  - We show by simulations that a nonlinear optical loop mirror with birefringent
      fiber can have intensity-dependent transmission of vector soliton pulses with a
      50/50 coupler. Using this result we propose two mode-locked laser cavity designs.

PMID- 18071512
TI  - Optically addressed direct-view display based on bacteriorhodopsin.
AB  - First experimental results from a direct-view display made from bacteriorhodopsin
      (BR) are presented. A dielectric mirror in direct contact with the photoactive BR
      layer forms the core of the BR display. The dielectric layer both decreases the
      light intensity necessary for writing and protects the observer from transmitted
      laser light. By illuminating the BR display with a suitably filtered light source
      from the rear we achieve the result that the information appears to the observer
      with an intensity contrast of more than 70:1, accompanied by a significant color
      shift. The combination of both enhances the visibility of and the ability to
      discern the information significantly. On the BR display the information appears
      in yellow on a dark purple-red background.

PMID- 18071513
TI  - Laser emission of erbium-doped fluoride bulk glasses in the spectral range from
      2.7 to 2.8 mum.
AB  - We report on the laser emission of erbium-doped fluoride glasses in the spectral
      range from 2.7 to 2.8 mum . The pump source was a fiber-coupled InGaAs
      semiconductor laser emitting near lambda(p)~970 nm . The laser performance of
      bulk samples with various ErF(3) contents was investigated with respect to the
      optimum doping concentration, which is estimated to be higher than 8 mol. %. A
      maximum output power of P(out) > 160 mW and a slope efficiency of eta = 10% were
      achieved. Results are compared with previously published data on erbium-doped
      ZBLAN fiber and LiYF(4) crystal lasers.

PMID- 18071514
TI  - Diode-pumped 1-W continuous-wave Er:YAG 3-mum laser.
AB  - We have demonstrated 1.15 W of Gaussianlike (M(2) = 2) cw output at 2.94 mum from
      a diode laser end-pumped monolithic laser crystal composed of Er-doped yttrium
      aluminum garnet (YAG) bonded to undoped YAG. The laser was pumped with two
      polarization-coupled 2.5-W flared laser diodes that provided a 45-mum pump waist
      with a low N.A. (<0.04) . Output at 2.94 mum was generated with a 34% slope
      efficiency and a greater-than-unity quantum efficiency.

PMID- 18071515
TI  - Passively Q-switched 0.1-mJ fiber laser system at 1.53 mum.
AB  - We demonstrate a passively Q-switched fiber laser system generating pulses with
      as much as 0.1 mJ of pulse energy at 1.53 mum and a >1-kHz repetition rate. These
      results were achieved with a simple master oscillator-power amplifier scheme with
      a single pump source, realized with large-mode-area fiber and multiple
      reflections upon a semiconductor saturable-absorber mirror.

PMID- 18071516
TI  - Characteristics of the intracavity dispersion in an erbium-doped fiber laser.
AB  - We have found theoretically that the intracavity dispersion of a laser is
      independent of the pumping power and wavelength and that the resonant group
      velocity dispersion vanishes. We have experimentally observed that the
      intracavity dispersion of an erbium-doped fiber laser was independent of the
      pumping power and wavelength within the measuring error, which agrees well with
      our theoretical predictions.

PMID- 18071517
TI  - Second-harmonic generation in a microradius LiNbO(3) cylinder with a quasi
      elliptical cross section.
AB  - LiNbO(3) single-crystal fibers with diameters of 63 and 230 mum were grown, and
      the second-harmonic-generation (SHG) process was studied with femtosecond laser
      pulses perpendicularly focused to the fiber. SHG occurred without collinear phase
      matching, leading to wavelength-independent overall conversion efficiency, unlike
      in a bulk crystal. The scattering pattern of the second harmonic exhibited an
      intense forward peak and an almost-uniform, less-intense distribution around the
      fiber, owing to trapping in high-Q whispering modes. Implementation of a second
      order autocorrelator with the 63-mum fiber demonstrates its application
      potential.

PMID- 18071518
TI  - Continuous-wave optical parametric oscillator based on periodically poled
      KTiOPO(4) and its application to spectroscopy.
AB  - We report a continuous-wave, doubly resonant optical parametric oscillator (OPO)
      based on the nonlinear material periodically poled KTiOPO(4) and its application
      to spectroscopy. The OPO, which is pumped by a diode-pumped frequency-doubled
      Nd:YLF laser at 523 nm, has a low pump-power threshold of 25 mW and can deliver
      10 mW of single-frequency output at 1.65 mum for a pump power of 200 mW. The
      idler wavelength can be temperature tuned at a rate of 0.73 nm/( degrees )C , and
      smooth tuning of the output frequency over ~3 GHz is achieved by smooth tuning of
      the pump laser. We demonstrate the practicality of the OPO by recording the
      absorption spectrum of methane near 1649 nm.

PMID- 18071519
TI  - Solitons of singly resonant optical parametric oscillators.
AB  - Single resonant parametric oscillators including intracavity quadratic and cubic
      nonlinearities are described in the mean-field limit with a cubic and quintic
      complex Ginzburg-Landau equation. Following our model, simple design criteria are
      derived for the generation of solitonlike pulses and beams for singly resonant
      optical parametric oscillators.

PMID- 18071520
TI  - High-frequency demodulation of multiphoton fluorescence in long-wavelength hyper
      Rayleigh scattering.
AB  - Suppression of the multiphoton fluorescence contribution to the hyper-Rayleigh
      (second-order nonlinear optical) scattering signal was recently achieved by
      intrinsic demodulation of the fluorescence at high amplitude-modulation (AM)
      frequencies [Olbrechts et al., Rev. Sci. Instrum. 69, 2233 (1998)]. These high AM
      frequencies were obtained from the high harmonic content in the Fourier spectrum
      of a repetitive train of femtosecond pulses from a Ti:sapphire laser emitting at
      800 nm. We have used a femtosecond parametric oscillator to shift the fundamental
      wavelength to 1.3 mum . By further improving the detection electronics, we can
      now obtain fluorescence suppression at AM frequencies up to 600 MHz. Fluorescence
      free hyperpolarizability values were obtained for fluorescent dipolar compounds
      as well as for an ionic fluorophore. The results also indicate that shifting the
      fundamental wavelength to the near infrared only is not a general solution to the
      multiphoton fluorescence problem in hyper-Rayleigh scattering.

PMID- 18071521
TI  - Tunable far-infrared spectroscopy extended to 9.1THz.
AB  - We synthesized tunable far-infrared radiation at frequencies higher than 9 THz
      (300 cm (-1)) by mixing CO(2) laser, (15)NH(3) laser, and microwave radiation in
      a W-Co metal-insulator-metal diode. We used this farinfrared radiation to
      accurately measure torsion-rotation transitions of CH(3)OH in the 8-9-THz region.
      We also measured the frequency of the aP(7, 3) (15)NH(3) laser transition.

PMID- 18071522
TI  - Simulation model for the effects of nonlinear polarization on the propagation of
      intense pulse lasers.
AB  - A simulation model including the effects of nonlinear polarization of a
      background neutral gas on the propagation of intense short pulse lasers is
      presented. The model includes the finite response time of the gas by using a soft
      core Coulombic potential for the bound electrons. A test problem for self
      focusing of a pulse is presented. Agreement with theoretical predictions for the
      self-focusing of an intense laser pulse in a gas with a finite-response-time
      nonlinear polarization included is found.

PMID- 18071523
TI  - Sub-two-cycle pulses from a Kerr-lens mode-locked Ti:sapphire laser.
AB  - Pulses shorter than two optical cycles with bandwidths in excess of 400 nm have
      been generated from a Kerr-lens mode-locked Ti:sapphire laser with a repetition
      rate of 90 MHz and an average power of 200 mW. Low-dispersion prisms and double
      chirped mirrors provide broadband controlled dispersion and high reflectivity.
      These pulse durations are to our knowledge the shortest ever generated directly
      from a laser oscillator.

PMID- 18071524
TI  - Femtosecond parametric generation in ZnGeP(2).
AB  - We report traveling-wave optical parametric generation in short (2-mm) ZnGeP(2)
      samples with reduced anomalous absorption, using femtosecond pump pulses near 2
      mum . The signal and the idler waves generated could be tuned from 2.5 to 10 mum
      , and they extend the tunability of the beta-barium borate optical parametric
      generator used as a pump source to the mid-infrared. At a single-pass internal
      conversion efficiency of 2.5% we estimate pulse durations of 75 fs (signal near 3
      mum) and 200 fs (idler near 6 mum).

PMID- 18071525
TI  - Low-repetition-rate high-peak-power Kerr-lens mode-locked TiAl(2)O(3) laser with
      a multiple-pass cavity.
AB  - We demonstrate a novel, long, multiple-pass cavity (MPC) to obtain low repetition
      rates and high peak intensities from Kerr-lens mode-locked lasers. We show that
      the MPC provides a zero effective length by a unity transformation of the q
      parameter after a given number of transits of the laser beam. Pulse durations of
      16.5 fs with 0.7 MW of power at a 15-MHz repetition rate are achieved. This is,
      to our knowledge, the lowest repetition rate ever achieved directly from a
      femtosecond laser resonator without use of additional active devices and cavity
      dumping. The combination of low repetition rates and high peak intensity is
      extremely useful for femtosecond pump-probe and other nonlinear experiments
      because it permits the application of high peak intensity without excessive
      average power.

PMID- 18071526
TI  - Soft-x-ray laser interferometry of a plasma with a tabletop laser and a Lloyd's
      mirror.
AB  - We report what is believed to be the first demonstration of soft-x-ray
      interferometry of a plasma with a tabletop soft-x-ray laser. A Lloyd's mirror
      interferometer was used in combination with a very compact lambda = 46.9 nm
      capillary-discharge-pumped laser to map the electron density in the cathode
      region of a pinch plasma.

PMID- 18071528
TI  - Excitation of morphology-dependent resonances and van de Hulst's localization
      principle.
AB  - When a laser beam scatters from a microparticle whose shape deviates from that of
      a sphere, a number of partial waves of the incident beam couple to a given
      partial wave of the scattered and interior fields. As a result, partial-wave
      coupling caused by small surface irregularities of a liquid droplet provides the
      mechanism for exciting low-radial-order morphology-dependent resonances.

PMID- 18071527
TI  - Soliton squeezing in a highly transmissive nonlinear optical loop mirror: errata.

PMID- 18071529
TI  - Poincare-sphere equivalent for light beams containing orbital angular momentum.
AB  - The polarization state of a light beam is related to its spin angular momentum
      and can be represented on the Poincare sphere. We propose a sphere for light
      beams in analogous orbital angular momentum states. Using the Poincare-sphere
      equivalent, we interpret the rotational frequency shift for light beams with
      orbital angular momentum [Phys. Rev. Lett. 80, 3217 (1998)] as a dynamically
      evolving geometric phase.

PMID- 18071530
TI  - Use of skew rays in multimode fibers to generate speckle field with nonzero
      vorticity.
AB  - Beams at the output of an axially symmetric multimode fiber were produced with
      mostly positive or negative values of angular index m through skew illumination
      of the input end of the fiber. In this way rays with predominantly positive or
      negative helicity were excited inside the fiber. The output cw speckle field at
      the wavelength lambda = 632.8 nm contained large densities N(+) and N(-) of wave
      front dislocations, or optical vortices, of both positive and negative sign.
      Vorticity was defined as V = N(+) - N(-) , was expressed analytically through the
      Wigner function of the field, and was found experimentally to be in good
      agreement with theory.

PMID- 18071531
TI  - Effect of the intermittent atmosphere on laser scintillations.
AB  - The evolution of the scintillation index of a spherical wave propagating through
      randomly varying profiles of the strength and the smallest scale of turbulence is
      calculated. These parameters were taken to be jointly log normal along the range.
      The specific parameters of the probability-density function that were used were
      taken from stratospheric experiments conducted by the U.S. Air Force.

PMID- 18071532
TI  - Three-dimensional optical metrology with color-coded extended depth of focus.
AB  - A novel method of rapid three-dimensional optical metrology that is based on
      triangulation of a configuration of color-coded light stripes is presented. The
      method exploits polychromatic illumination and a combined diffractive-refractive
      element, so the incident light is focused upon a stripe that is axially
      dispersed, greatly increasing the depth-measuring range without any decrease in
      the axial or the lateral resolution. The discrimination of each color stripe is
      further improved by spectral coding and decoding techniques. An 18-fold increase
      in the depth of focus was experimentally obtained while diffraction-limited light
      stripes were completely maintained.

PMID- 18071533
TI  - Optical path-length spectroscopy of wave propagation in random media.
AB  - We propose optical path-length spectroscopy as a new approach to obtaining
      information from media that exhibit multiple light scattering. By using a
      backscattering technique based on low-coherence interferometry, we are able to
      determine the optical path-length distribution for light reflected from a random
      medium and to infer the value of the transport mean free path. We illustrate how
      a diffusion approximation model leads to a satisfactory description of depth
      resolved profiles of the backscattered intensity and discuss potential
      applications of this technique.

PMID- 18071534
TI  - Header recognition by use of soliton interaction in fibers.
AB  - We report an experimental demonstration of optical header recognition that
      utilizes phase-dependent soliton interaction. A probe word composed of optical
      solitons is copropagated with a data word while cross-phase modulation from the
      data bits alters the soliton phases. During subsequent propagation the result of
      interaction between the solitons depends on the data pattern and is used to
      identify a desired data word. The method is noncorrelational, has a high
      contrast, and uses a pattern-detection threshold that does not depend on the
      desired data pattern. We have demonstrated recognition of 8-bit words at 63
      Gbits/s with this technique.

PMID- 18071535
TI  - Soliton collisions in wavelength-division-multiplexed dispersion-managed systems.
AB  - In dense wavelength-division-multiplexed transmission with strong dispersion
      management, most pulses inevitably have many partial collisions with pulses of an
      interacting channel. These partial collisions, in conjunction with the effects of
      complete collisions, tend to produce unacceptably large timing jitter in high-bit
      rate, long-distance transmission. With the use of frequency-guiding filters,
      however, the timing jitter is dramatically reduced and tends to remain
      indefinitely clamped to acceptably small levels.

PMID- 18071536
TI  - Frequency modulation via the Doppler effect in optical fibers.
AB  - We present the principle of optical frequency modulation via the Doppler effect
      obtained by rapidly stretching an optical fiber and thus modifying the optical
      path of the light propagating in the fiber. This procedure creates a pure
      frequency shift, with no degradation of the spectrum. Moreover, the effect is
      wavelength independent and can therefore be applied to any type of light source.
      We show an experimental realization in which a frequency excursion of ~100 MHz
      was obtained with a bobbin vibrating at 180 Hz.

PMID- 18071537
TI  - All-optical control of Bragg grating in semiconductor-coated D-shaped fiber.
AB  - A Bragg grating was fabricated in a D-shaped fiber that was subsequently coated
      with an alpha-Si:H semiconductor film. The reflected spectrum was optically
      controlled by means of evanescent coupling, shifting to shorter wavelengths with
      increased control-light power. The effective nonlinearity of the fiber was 2.0 x
      10(-10) cm(2)/W . The device was optically tuned by 4.3 x 10(-4) nm/mW , leading
      to 54% (>3-dB) depth modulation for 230 mW of power.

PMID- 18071538
TI  - Laser surface profiler.
AB  - By accurate measurement of the angle of reflection of a laser beam that is
      incident upon a reflective surface with a position-sensitive detector, changes in
      the surface-normal direction (the slope or the derivative of the surface) can be
      determined directly. An instrument has been built that makes repeated
      measurements over the surface and uses the collected data to produce a gray-scale
      image of the slope. The resolution of this system for detecting changes in the
      surface-normal direction is found to be better than 0.01 degrees . By focusing of
      the laser beam to achieve a lateral resolution of 5 mum , the resolvable surface
      height change owing to a variation in slope is estimated to be <1 nm .

PMID- 18071539
TI  - Solgel grating waveguides for distributed Bragg reflector lasers.
AB  - Solgel grating waveguides and their application to the fabrication of external
      cavity distributed Bragg reflector (DBR) lasers are demonstrated. A new
      composition of aluminosilicate material is developed for the fabrication of
      single-mode waveguides and Bragg reflectors. An average loss of <0.2 dB/cm is
      measured in the single-mode waveguides at 1550 nm. The reflectors show filtering
      greater than 97% near 1530 nm, with a bandwidth of ~0.6 nm . The Bragg reflectors
      are used as feedback resonators for DBR lasers. Single-mode lasing with a
      sidemode suppression of better than 25 dB is demonstrated.

PMID- 18071540
TI  - Correlation of ultraviolet-induced stress changes and negative index growth in
      type IIa germanosilicate waveguide gratings.
AB  - The stress anisotropy in planar germanosilicate waveguides is used to follow the
      changes in stress, measured as a birefringence, with UV irradiation. Compressive
      stress increases with the growth of the negative index grating, saturating when
      the grating modulation saturates.

PMID- 18071541
TI  - Demonstration of optical synchronization of chaotic external-cavity laser diodes.
AB  - An experimental demonstration of optical synchronization of chaotic external
      cavity semiconductor laser diodes is reported for what is believed to be the
      first time. It is shown that at an optimum coupling strength between the master
      and the slave lasers high-quality synchronization can be obtained.

PMID- 18071542
TI  - All-solid-state neodymium-based single-frequency master-oscillator fiber power
      amplifier system emitting 5.5 W of radiation at 1064 nm.
AB  - We demonstrate a master-oscillator fiber power-amplifier system consisting of a
      diode-pumped monolithic nonplanar ring oscillator as the master oscillator and a
      Nd:glass double-clad fiber as the power amplifier. The system emits up to 5.5 W
      of single-frequency radiation at a wavelength of 1064 nm with an M(2) value of
      ~1.1 . The optical emission spectrum is investigated with respect to the
      background of residual amplified spontaneous emission. Spectrally resolved
      amplitude-noise behavior is examined. Further power-scaling possibilities are
      discussed.

PMID- 18071543
TI  - Coherent versus incoherent modulation of a resonant level: the effect of
      modulation noise on the propagation of light through quantum wells.
AB  - The propagation of a weak light beam through a quantum well in the vicinity of an
      excitonic resonance that is modulated harmonically in time at terahertz frequency
      is considered. It is found that the reflection probability of the light beam is
      considerably different in the cases of purely coherent versus Gaussian incoherent
      terahertz modulation, even in the limit of long coherence times.

PMID- 18071544
TI  - Directional coupler with soliton-induced waveguides.
AB  - We demonstrate a directional coupler that employs two waveguides induced by two
      mutually incoherent photorefractive solitons propagating in parallel at close
      proximity. Efficient coupling from one waveguide to the other is achieved for
      probe beams at wavelengths much longer than that of the solitons. We study the
      mutual coupling as a function of distance between solitons.

PMID- 18071545
TI  - One-dimensional coherent four-wave mixing as a way to image the spatial
      distribution of atoms in a laser-produced plasma.
AB  - An experimental technique based on coherent one-dimensional hyper-Raman-resonant
      four-wave mixing in broad cylindrically focused light beams has been developed
      for line-by-line imaging of spatial distribution of excited atoms in a low
      temperature plasma of optical breakdown. The technique was applied to map excited
      lead atoms in a low-temperature laser-produced plasma.

PMID- 18071546
TI  - Second-harmonic generation in a direct-bonded periodically poled LiNbO(3) buried
      waveguide.
AB  - We report the fabrication of a 12-mum -thick periodically poled LiNbO(3) planar
      waveguide buried in LiTaO(3) by direct bonding of precision-polished surfaces.
      Frequency doubling of the 1064-nm output of a cw diode-pumped Nd:YAG laser was
      performed in a 5.5-mm-long device with a 6.50-mum -period grating at an elevated
      temperature of 174 degrees C. The resultant green second-harmonic output
      exhibited fundamental-spatial-mode characteristics at a 4.3%W(-1) conversion
      efficiency.

PMID- 18071547
TI  - Optical triangular-partition fuzzy systems with one-memory-matrix fuzzy
      associative memory.
AB  - Taking advantage of the special properties of fuzzy sets, we propose that one
      memory-matrix fuzzy associative memory can be used to realize triangular
      partition fuzzy inference systems efficiently. The proposed model has perfect
      recall capability.

PMID- 18071548
TI  - Recording media that exhibit high dynamic range for digital holographic data
      storage.
AB  - A general strategy for fabricating thick, optically flat photopolymer recording
      media with high dynamic range (M/#) that exhibit low levels of recording-induced
      Bragg detuning for holographic data storage is presented. In particular, media
      with M/# values as high as 42 in 1-mm-thick formats are obtained. We believe that
      these results are the first demonstration of a holographic storage medium with a
      dynamic range of this magnitude. In addition, we report the holographic recording
      and recovery of high-capacity (480-kbit) digital data pages in these media,
      further illustrating their data-storage capabilities.

PMID- 18071549
TI  - Evolving FROGS: phase retrieval from frequency-resolved optical gating
      measurements by use of genetic algorithms.
AB  - We present a new technique based on genetic algorithms for retrieving the
      electric field and the phase of ultrashort pulses from frequency-resolved optical
      gating (FROG) traces. We have successfully applied a very basic genetic algorithm
      to the two most common beam geometries: polarization gate and second-harmonic
      generation (SHG). In the case of SHG FROG, the genetic algorithm returns a lower
      error than the standard iterative composite algorithm.

PMID- 18071550
TI  - Pulse compression by use of deformable mirrors.
AB  - An electrostatically deformable, gold-coated, silicon nitride membrane mirror was
      used as a phase modulator to compress pulses from 92 to 15 fs. Both an iterative
      genetic algorithm and single-step dispersion compensation based on frequency
      resolved optical gating calibration of the mirror were used to compress pulses to
      within 10% of the transform limit. Frequency-resolved optical gating was used to
      characterize the pulses and to test the range of the deformable-mirror-based
      compressor.

PMID- 18071551
TI  - Frequency-domain interferometric second-harmonic spectroscopy.
AB  - We report a new spectroscopic technique to measure simultaneously the intensity
      and the phase of second-harmonic (SH) radiation over a broad spectral range
      without laser tuning. Temporally separated SH pulses from two sources, excited by
      the same broad-bandwidth 15-fs Ti:sapphire fundamental pulse, interfere in a
      spectrometer to yield frequency-domain interference fringes. We demonstrate the
      technique by measuring the strongly bias-dependent phase of SH radiation from a
      Si/SiO(2)/Cr metal-oxide-semiconductor capacitor in the spectral range of the
      SiE(1) critical point.

PMID- 18071552
TI  - High-repetition-rate 300-ps pulsed ultraviolet source with a passively Q-switched
      microchip laser and a multipass amplifier.
AB  - We demonstrate a new kind of picosecond laser source in the UV at a high
      repetition rate of -45 kHz , using only passive, compact, and simple elements.
      This system is based on a microchip laser and a very efficient multipass
      amplifier, both pumped with recently developed high-brightness laser diodes. The
      system has been optimized to deliver, at a high repetition rate, subnanosecond
      pulses at the wavelength 355 nm with an energy per pulse of close to 1 muJ (38-mW
      average power). This source is to our knowledge the first totally passive 300-ps
      UV laser source at this high repetition rate.

PMID- 18071553
TI  - Binary optics and confocal imaging.
AB  - The use of two-level phase masks or spatial light modulators in confocal imaging
      systems is considered. It is shown how, although such masks can modify or correct
      the effective point-spread function of a system, their behavior for planar
      objects may not be as desired as a result of phase-wrapping effects. Overcoming
      this problem with a multilevel mask or a pair of two-level masks is discussed.

PMID- 18071554
TI  - Dispersion management with filtering.
AB  - We present analytical and numerical results for dispersion-managed solitons in a
      fiber link including guiding filters and compensating gain, both taken in the
      distributed approximation. Stationary propagation regimes with anomalous, zero,
      and normal path-average dispersion (PAD) are identified. New features, compared
      with those of the case without filters, are the absence of a critical strength
      for propagation at zero and normal PAD and, instead, the existence of a critical
      power for stationary propagation at any PAD.

PMID- 18071555
TI  - Characterization of the Brillouin-loss spectrum of single-mode fibers by use of
      very short (<10-ns) pulses.
AB  - The characterization of the Brillouin-loss spectrum of single-mode fibers with
      very short (<10-ns) pulses has been studied. It was found that the Brillouin-loss
      signal intensity is linearly related to the duration of the pump pulse used to
      obtain the spectrum. In contrast with the uniform trend of the signal, three
      distinct behaviors were observed in the spectral linewidth. At long pulse
      durations the linewidth was constant at approximately 40 MHz. Pulse durations of
      the order of the phonon lifetime resulted in a broader spectrum, reaching a
      maximum width of ~100 MHz at 5 ns. Reducing the pulse duration further resulted
      in a sudden narrowing of the Brillouin line.

PMID- 18071556
TI  - Zinc-tetrabenzoporphyrine-doped poly(methyl methacrylate): a new photochromic
      recording medium.
AB  - A photochromic reaction in Zn-tetrabenzoporphyrine-doped poly(methyl
      methacrylate) was investigated at room temperature. A one-quantum
      thermoreversible photoreaction could be initiated in the sample with 633-nm He-Ne
      laser irradiation. The photoreaction quantum yield depended strongly on the
      concentration of an additional electron acceptor. The changes of the refractive
      index were also measured.

PMID- 18071557
TI  - Arresting ultraviolet-laser damage in fused silica.
AB  - The 351-nm laser-damage initiation threshold for surface damage in conventionally
      polished fused silica is demonstrated to be stress dependent. By circumferential
      application of modest loads to a sample, a controllable stress field can be
      established within the clear aperture of a fused-silica specimen, in response to
      which both the damage-initiation fluence and the crack-propagation fluence
      requirements are increased above those for unstressed conditions.

PMID- 18071558
TI  - Spatially resolved spectral interferometry for determination of subsurface
      structure.
AB  - We describe an instrument capable of obtaining two-dimensional images of
      subsurface structure in real time with no moving parts. The technique is based on
      spectral interferometry and uses an imaging spectrograph to obtain spatially
      resolved spectra. A test sample consisting of microscope coverslips and a Ronchi
      grating was measured, illustrating the system's depth resolution of 38 mum and
      transverse resolution of at least 12.7 mum . The technique is readily adaptable
      to endoscopic delivery as well as three-dimensional real-time image acquisition.

PMID- 18071559
TI  - Accurate monitoring of an interferometric fiber-optic sensor with a multimode
      semiconductor laser.
AB  - A technique for monitoring interferometric sensors by correlation of the optical
      signal from the sensor with the signal from a phase-modulated reference
      interferometer is described. The technique is applied to temperature measurement
      with a fiber Fabry-Perot sensing head. We extend the 7 degrees C unambiguous
      measurement range obtained with a 1.3-mum laser diode as the light source to 43
      degrees C by adding a second laser diode emitting at 1.55mum . Experimentally, a
      rms phase-measurement error of +/-0.28rad , corresponding to a temperature error
      of +/-0.32 degrees C , was achieved with a low-quality multimode Fabry-Perot
      laser. The phase error was improved to +/-0.14rad , corresponding to a
      temperature error of +/-0.16 degrees C , by use of a distributed-feedback laser
      diode.

PMID- 18071560
TI  - Integrated optical Bragg-grating-based chemical sensor on a curved input edge
      waveguide structure.
AB  - A novel integrated optical chemical sensor based on a surface-relief Bragg
      grating in a waveguide with a curved input edge, and coated with a chemically
      sensitive polysiloxane cladding, is described. The curved edge provides a
      mechanism within the device fabrication that allows for alignment of the input
      beam to the grating to achieve Bragg scattering. As proof of principle, a low
      parts-in-10(6) toluene-vapor sensor with a fast response time is demonstrated.

PMID- 18071561
TI  - Diode-pumped passively mode-locked Nd:YAG laser with 10-W average power in a
      diffraction-limited beam.
AB  - We present a passively mode-locked Nd:YAG laser with 10.7-W average output power
      in a diffraction-limited beam. Stable self-starting mode locking with a pulse
      duration of 16 ps and a pulse energy of 120 nJ is obtained with a semiconductor
      saturable-absorber mirror. The laser is directly side pumped with two 20-W diode
      bars. Single-pass frequency doubling in an external 5-mm-thick KTP crystal yields
      3.2-W average power at 532 nm.

PMID- 18071562
TI  - Power-efficient nonreciprocal interferometer and linear-scanning fiber-optic
      catheter for optical coherence tomography.
AB  - A nonreciprocal fiber-optic interferometer is demonstrated in an optical
      coherence tomography (OCT) system. The increased power efficiency of this system
      provides a 4.1-dB advantage over standard Michelson implementations. In addition,
      a new linear-scanning fiber-optic catheter is demonstrated that avoids the rotary
      optical junction that is required in circumferential scanning systems. These
      advancements have permitted the clinical implementation of OCT imaging in the
      human gastrointestinal tract.

PMID- 18071563
TI  - Simultaneous reconstruction of absorption and scattering images by multichannel
      measurement of purely temporal data.
AB  - We present what is believed to be the first simultaneous reconstruction of the
      internal scattering and absorbing properties of a highly scattering medium by use
      of purely temporal data. These results are also the first acquired with the
      multichannel time-resolved imaging system developed at University College London.

PMID- 18071564
TI  - Two-dimensional depth-resolved Mueller matrix characterization of biological
      tissue by optical coherence tomography.
AB  - We built a polarization-sensitive optical coherence tomographic system and
      measured the two-dimensional depth-resolved full 4 x 4 Mueller matrix of
      biological tissue for what is believed to be the first time. The Mueller matrix
      measurements, which we made by varying the polarization states of the light
      source and the detector, yielded a complete characterization of the polarization
      property of the tissue sample. The initial experimental results indicated that
      this new approach reveals some tissue structures that are not perceptible in
      standard optical coherence tomography.

PMID- 18071565
TI  - Using a grating structure for phase compensation in achieving an efficient round
      trip optical parametric process in periodically poled lithium niobate with an
      incomplete quasi-phase-matching period.
AB  - An incomplete period of the last quasi-phase-matching (QPM) segment in a
      periodically poled nonlinear crystal represents a key problem in implementing a
      nonlinear wavelength-conversion device with round-trip or oscillating waves of
      interaction. Such a segment at the crystal end implies broken QPM periodicity for
      the reflected waves of interaction. We demonstrate numerically that with a
      grating structure at the crystal end for the reflecting signal the wavelength
      dependent phase shift at Bragg reflection can compensate for the phase mismatch
      of the reflected signal, idler, and pump of an optical parametric process.
      Therefore, by slightly shifting the signal wavelength we can maintain the phase
      matching condition with any length of the last QPM segment. It is shown that with
      a grating structure the conversion efficiency of the round-trip optical
      parametric process can always be optimized.

PMID- 18071566
TI  - Determination of weak optical pulses in amplitude and phase by measurement of the
      transient polarization state.
AB  - Unlike in established methods, the phase of an optical pulse is calculated from a
      single time transient in combination with a single spectrum of its polarization
      state: For dynamically changing elliptical polarizations the vectorial nature of
      the electromagnetic radiation results in two independent constraints that
      uniquely determine the chirp and the spectral phase. The practical feasibility of
      the method is demonstrated, a phase of a four-wave-mixing signal from a
      semiconductor single quantum well with a pulse energy of only 0.5 fJ is
      determined, and the accuracy of the setup is analyzed by a numerical simulation.

PMID- 18071567
TI  - Parity coding for page-oriented optical memories with intrapage intensity
      variations.
AB  - A new form of modulation coding for page-oriented memories (POM's) based on
      parity is introduced. The parity-based codes are evaluated by use of simulated
      POM data pages. It is illustrated that the proposed parity codes can outperform
      balanced modulation codes in the presence of fixed-pattern noise and additive
      white Gaussian noise.

PMID- 18071568
TI  - Microfabrication by use of a spatial light modulator in the ultraviolet:
      experimental results.
AB  - We report the development of a new microstereophotolithography technique for
      creation of three-dimensional microcomponents by use of a planar, layer-by-layer
      process of exposure, in which a spatial light modulator is used as a dynamic
      lithographic mask. The system operates in the UV to take advantage of the wide
      supply of commercially available photopolymers designed for conventional
      stereolithography. With this novel procedure it is possible to build components
      with feature sizes as small as a few micrometers. The experimental setup is
      briefly described, and the first microcomponent fabricated by this system is
      shown.

PMID- 18071569
TI  - Microwave-induced transient parametric gratings.
AB  - We propose a new method for the formation of light-induced transient gratings in
      microwave-biased semiconductor crystals that exhibit a negative differential
      resistivity. Nonuniform heating of the electron gas in alternating electric
      fields induces spatially periodic modulation of the refractive index with spacing
      that is tunable by the external field frequency. Numerical simulations performed
      on a bulk GaAs sample prove that transient parametric gratings of both free
      carrier and electro-optic origin can be triggered by a spatially modulated light
      pattern or by uniform photoexcitation.

PMID- 18071570
TI  - Stable mode-locking operation in a Cr:forsterite laser with a five-mirror cavity.
AB  - The experimental finding of more-stable mode-locking operation in a five-mirror
      cavity than in a conventional four-mirror cavity for a Cr:forsterite laser [IEEE
      J. Quantum Electron. 33, 1975 (1997)] was interpreted by ABCD-matrix formalism.
      Since the optimum cavity configuration operation for mode-locking operation was
      attainable in the middle of the stable cavity condition, we conclude that one can
      easily achieve KLM alignment and stable mode locking with a five-mirror cavity.

PMID- 18071571
TI  - Subfemtosecond pulse generation by rotational molecular modulation.
AB  - We extend a recent suggestion for the generation of subfemtosecond pulses by
      molecular modulation [Phys. Rev. Lett. 81, 2894 (1998)] to the rotational
      spectrum of molecular hydrogen (H(2)) . When a rotational transition |a? ? |b? is
      strongly driven (|rho(ab) |=0.5) the generation and phase-slip lengths are of the
      same order and the Raman spectrum has approximately Bessel function sideband
      amplitudes. Numerical simulation predicts that this spectrum (generated in a 14
      cm-long cell at 1-atm pressure of H(2)) will compress into a train of pulses with
      94-fs pulse separation and a pulse length of 0.5 fs.

PMID- 18071572
TI  - Two-pulse nondegenerate excitation of electron-hole wave packets in quantum
      wells: tunable terahertz emission.
AB  - It was shown recently that driving an optically excited quantum well with a
      terahertz (THz) frequency electric field can lead to higher-harmonic generation
      in the THz regime: the THz analog of the dynamic Franz-Keldysh effect. We propose
      a new double-pulse excitation method that not only increases the efficiency of
      the harmonic generation but is also able to control somewhat the dominant
      upshifted harmonic of the THz radiation by means of selective excitation of
      spatially chosen electron-hole relative motion wave packets.

PMID- 18071573
TI  - Spatial temporal wave mixing for space time conversion.
AB  - A nonlinear optical processor that is capable of true real-time conversion of
      spatial-domain images to ultrafast time-domain optical waveforms is presented.
      The method is based on four-wave mixing between the optical waves of spectrally
      decomposed ultrashort pulses and spatially Fourier-transformed quasi
      monochromatic images. To achieve efficient wave mixing at a femtosecond rate we
      utilize a cascaded second-order nonlinearity arrangement in a beta-barium borate
      crystal with type II phase matching. We use this ultrafast technique to
      experimentally generate several complex-amplitude temporal waveforms, with
      efficiency as high as 10%, by virtue of the cascaded nonlinearity arrangement.

PMID- 18071574
TI  - High-power chirped-pulse all-fiber amplification system based on large-mode-area
      fiber gratings.
AB  - We describe the fabrication of chirped gratings in a specially developed
      photosensitive large-mode-area fiber and report the use of these components in a
      picosecond all-fiber chirped-pulse-amplification circuit. We demonstrate the
      generation of microjoule energy pulses with peak powers in excess of 500 kW,
      which we believe to be a record peak power from an all-fiber system.

PMID- 18071575
TI  - Amplitude and phase characterization of weak blue ultrashort pulses by
      downconversion.
AB  - We present difference-frequency generation cross-correlation frequency-resolved
      optical gating, a new method of characterizing the amplitude and phase of weak
      ultrashort pulses in the blue spectral region. The method uses the spectrally
      resolved downconversion signal of the blue pulse and a fully characterized
      reference pulse with a lower center frequency. The amplitude and phase of the
      blue test pulse are retrieved from the corresponding spectrogram and electric
      field of the reference pulse with an interactive Fourier-transform algorithm.

PMID- 18071576
TI  - Metal-Enhanced S(2) Fluorescence from Azulene.
AB  - In this paper, we report the first observation of metal-enhanced S(2) emission at
      room and low temperature (77K). The S(2) emission intensity of Azulene is
      enhanced by close proximity to Silver island films (SiFs). In this regard, a ~ 2
      fold higher S(2) fluorescence intensity of Azulene was observed from SiFs as
      compared to a glass control sample. This suggests that S(2) excited states can
      couple to surface plasmons and enhance S(2) fluorescence yields, a helpful
      observation in our understanding the interactions between plasmons and
      lumophores, and our continued efforts to develop a unified plasmon
      lumophore/fluorophore theory.

PMID- 18071577
TI  - Synthesis and cyclometalation of a pyrido[3,2-e]-2,10b-diaza
      cyclopenta[c]fluorene-1,3-dione scaffold.
AB  - The synthesis of a pyrido[3,2-e]-2,10b-diaza-cyclopenta[c]fluorene-1,3-dione
      scaffold is disclosed, which was synthesized using a Suzuki cross-coupling
      reaction and an intramolecular Heck cyclization as the key steps. This
      heterocyclic system can serve as a bidentate ligand as demonstrated by the
      formation and structural analysis of a derived ruthenium complex. The new
      scaffold constitutes an interesting candidate for the development of
      organometallic protein kinase inhibitors.

PMID- 18071579
TI  - CHRONIC INSOMNIA AND STRESS SYSTEM.
AB  - SynopsisIn insomnia, which is a very common sleep disorder, objective sleep
      measures, EEG activity, physiologic findings, HPA axis activity and inflammation
      markers suggest that it is not a state of sleep loss, but a disorder of
      hyperarousal present both during the night and the daytime. Several psychological
      and physiological factors contribute to the onset and perpetuation of insomnia,
      such as anxious-ruminative personality traits, stressful events, age-related
      sleep homeostasis weakening mechanisms, menopause and biologic - genetic
      diathesis of CNS hyperarousal. The therapeutic approach in insomnia should be
      multidimensional reducing the overall emotional and physiologic hyperarousal and
      its underlying factors present throughout the 24-h sleep/wake period.

PMID- 18071580
TI  - A new palladium-mediated approach to 4-N-arylamino-1-butanols from peroxidic
      tetrahydrofuran and primary aromatic amines.
AB  - Reaction of primary aromatic amines with peroxidic tetrahydrofuran (THF) in the
      presence of hydrogen and 10% palladium on carbon catalyst results in THF ring
      opening to give 4-N-arylamino-1-butanols in good yield. The reaction mechanism is
      believed to involve a free-radical sequence resulting in an imino alcohol
      subsequently reduced to product.

PMID- 18071581
TI  - The temporal dynamics of ambiguity resolution: Evidence from spoken-word
      recognition.
AB  - Two experiments examined the dynamics of lexical activation in spoken-word
      recognition. In both, the key materials were pairs of onset-matched picturable
      nouns varying in frequency. Pictures associated with these words, plus two
      distractor pictures were displayed. A gating task, in which participants
      identified the picture associated with gradually lengthening fragments of spoken
      words, examined the availability of discriminating cues in the speech waveforms
      for these pairs. There was a clear frequency bias in participants' responses to
      short, ambiguous fragments, followed by a temporal window in which discriminating
      information gradually became available. A visual-world experiment examined speech
      contingent eye-movements. Fixation analyses suggested that frequency influences
      lexical competition well beyond the point in the speech signal at which the
      spoken word has been fully discriminated from its competitor (as identified using
      gating). Taken together, these data support models in which the processing
      dynamics of lexical activation are a limiting factor on recognition speed, over
      and above the temporal unfolding of the speech signal.

PMID- 18071578
TI  - Fundulus as the premier teleost model in environmental biology: opportunities for
      new insights using genomics.
AB  - A strong foundation of basic and applied research documents that the estuarine
      fish Fundulus heteroclitus and related species are unique laboratory and field
      models for understanding how individuals and populations interact with their
      environment. In this paper we summarize an extensive body of work examining the
      adaptive responses of Fundulus species to environmental conditions, and describe
      how this research has contributed importantly to our understanding of physiology,
      gene regulation, toxicology, and ecological and evolutionary genetics of teleosts
      and other vertebrates. These explorations have reached a critical juncture at
      which advancement is hindered by the lack of genomic resources for these species.
      We suggest that a more complete genomics toolbox for F. heteroclitus and related
      species will permit researchers to exploit the power of this model organism to
      rapidly advance our understanding of fundamental biological and pathological
      mechanisms among vertebrates, as well as ecological strategies and evolutionary
      processes common to all living organisms.

PMID- 18071582
TI  - Self-rated health showed a consistent association with serum HDL-cholesterol in
      the cross-sectional Oslo Health Study.
AB  - OBJECTIVE: To examine the association between serum HDL-cholesterol concentration
      (HDL-C) and self rated health (SRH) in several age groups of men and women. STUDY
      DESIGN AND SETTING: The study had a cross-sectional design and included 18,770
      men and women of the Oslo Health Study aged 30; 40 and 45; 69-60; 75-76 years.
      RESULTS: In both sexes and all age groups, SRH (3 categories: poor, good, very
      good) was positively correlated with HDL-C. Logistic regression analysis on
      dichotomized values of SRH (i.e. poor vs. good health) in each age group of men
      and women showed that increasing HDL-C values were associated with increasing
      odds for reporting good health; the odds ratio (OR) was highest in young men, and
      was generally lower in women than in men. Odds ratios in the 4 age groups of men
      were 4.94 (2.63-9.29), 2.25 (1.63-3.09), 2.12 (1.58-2.86), 1.87 (1.37-2.54); and
      in women: 3.58 (2.46-5.21), 2.81 (2.23-3.53), 2.28 (1.84-2.82), 1.61 (1.31-1.99).
      In the whole material, 1 mmol/L increase in HDL-C increased the odds for
      reporting good health by 2.27 (2.06-2.50; p<0.001), when adjusting for sex, age
      group, time since food intake and use of cholesterol lowering drugs. Chronic
      diseases, pain, psychological distress, smoking, alcohol, length of education,
      and dietary items did not have any major influence on the pattern of the HDL-C
      vs. SRH association. CONCLUSION: There was a consistent positive association
      between HDL-C and SRH, in both men and women in four different age groups, with
      the strongest association in young people.

PMID- 18071583
TI  - Association of adiposity, cardiorespiratory fitness and exercise practice with
      the prevalence of type 2 diabetes in Brazilian elderly women.
AB  - BACKGROUND: Diabetes incidence in people with advanced age is increasing at an
      alarming rate, and for this reason the screening of high-risk individuals such as
      elderly women is critically important. OBJECTIVE: To analyze the association of
      adiposity, cardiorespiratory fitness and exercise practice with type 2 diabetes
      (T2D) in elderly Brazilian women. METHODS: Participated of this cross sectional
      study 1,059 elderly women (mean 69.5 yr; SD 6.1), who self-reported family
      history of cardiovascular disease, smoking status, hypertension, and T2D
      diagnosed previously by a physician. The following independent variables were
      assessed: exercise practice, body mass index, waist circumference, and
      cardiorespiratory fitness. Logistic regression analysis was used to investigate
      the association between each independent variable with T2D using adjusted-models.
      RESULTS: T2D prevalence was 16%. General and central adiposity were directly
      associated with T2D, whereas cardiorespiratory fitness was inversely related with
      T2D. The joint effect of exercise practice and central adiposity showed that
      inactive women had higher odds ratio for T2D when compared with active ones,
      within the same WC group. Inactive women with WC > or = 94.0 cm had an odds ratio
      of 5.8 (95%IC 1.3-25.3). CONCLUSIONS: A direct positive association was found
      between general and central adiposity, as well as an inverse relation between CRF
      and exercise practice with T2D. Elderly women who practice exercise regularly had
      lower odds for T2D. Health professionals should encourage individuals of all ages
      to engage on regular exercise practice, which could reduce body fatness and may
      be beneficial in reducing the prevalence of T2D in older ages.

PMID- 18071584
TI  - cDNA cloning and overexpression of acidic ribosomal phosphoprotein P1 gene
      (RPLP1) from the giant panda.
AB  - RPLP1 is one of acidic ribosomal phosphoproteins encoded by RPLP1 gene, which
      plays an important role in the elongation step of protein synthesis. The cDNA of
      RPLP1 was cloned successfully for the first time from the Giant Panda (Ailuropoda
      melanoleuca) using RT-PCR technology, which was also sequenced, analyzed
      preliminarily and expressed in E.coli. The cDNA fragment cloned is 449bp in size,
      containing an open reading frame of 344bp encoding 114 amino acids. Alignment
      analysis indicated that the nucleotide sequence and the deduced amino acid
      sequence are highly conserved to other five species studied, including Homo
      sapiens, Mus musculus, Rattus norvegicus, Bos Taurus and Sus scrofa. The
      homologies for nucleotide sequences of Giant Panda PPLP1 to that of these species
      are 92.4%, 89.8%, 89.0%, 91.3% and 87.5%, while the homologies for amino acid
      sequences are 96.5%, 94.7%, 95.6%, 96.5% and 88.6%. Topology prediction showed
      there are three Casein kinase II phosphorylation sites and two N-myristoylation
      sites in the RPLP1 protein of the Giant Panda (Ailuropoda melanoleuca). The RPLP1
      gene was overexpressed in E. coli and the result indicated that RPLP1 fusion with
      the N-terminally His-tagged form gave rise to the accumulation of an expected
      18kDa polypeptide, which was in accordance with the predicted protein and could
      also be used to purify the protein and study its function.

PMID- 18071586
TI  - Rational design of analyte channels of the green fluorescent protein for
      biosensor applications.
AB  - A novel solvent-exposed analyte channel, generated by F165G substitution, on the
      surface of green fluorescent protein (designated His(6)GFPuv/F165G) was
      successfully discovered by the aid of molecular modeling software (PyMOL) in
      conjunction with site-directed mutagenesis. Regarding the high predictive
      performance of PyMOL, two pore-containing mutants namely His(6)GFPuv/H148G and
      His(6)GFPuv/H148G/F165G were also revealed. The pore sizes of F165G, H148G, and
      the double mutant H148G/F165G were in the order of 4, 4.5 and 5.5 A,
      respectively. These mutants were subjected to further investigation on the effect
      of small analytes (e.g. metal ions and hydrogen peroxide) as elucidated by
      fluorescence quenching experiments. Results revealed that the F165G mutant
      exhibited the highest metal sensitivity at physiological pH. Meanwhile, the other
      2 mutants lacking histidine at position 148 had lower sensitivity against Zn(2+)
      and Cu(2+) than those of the template protein (His(6)GFPuv). Hence, a significant
      role of this histidine residue in mediating metal transfer toward the GFP
      chromophore was proposed and evidently demonstrated by testing in acidic
      condition. Results revealed that at pH 6.5 the order of metal sensitivity was
      found to be inverted whereby the H148G/F165G became the most sensitive mutant.
      The dissociation constants (K(d)) to metal ions were in the order of 4.88 x 10(
      6) M, 16.67 x 10(-6) M, 25 x 10(-6) M, and 33.33 x 10(-6) M for
      His(6)GFPuv/F165G, His(6)GFPuv, His(6)GFPuv/H148G/F165G and His(6)GFPuv/H148G,
      respectively. Sensitivity against hydrogen peroxide was in the order of
      H148G/F165G > H148G > F165G indicating the crucial role of pore diameters.
      However, it should be mentioned that H148G substitution caused a markedly
      decrease in pH- and thermo-stability. Taken together, our findings rendered the
      novel pore of GFP as formed by F165G substitution to be a high impact channel
      without adversely affecting the intrinsic fluorescent properties. This opens up a
      great potential of using F165G mutant in enhancing the sensitivity of GFP in
      future development of biosensors.

PMID- 18071587
TI  - The growth-hormone inducible transmembrane protein (Ghitm) belongs to the Bax
      inhibitory protein-like family.
AB  - The conserved protein domain UPF0005 is a protein family signature distributed
      among many species including fungi and bacteria. Although of unknown
      functionality this motif has been found in newly identified antiapoptotic
      proteins comprising the BI-1 family, namely Bax-inhibitory Protein-1 (BI-1),
      Lifeguard (LFG), and h-GAAP. In a search for vertebrate proteins presumably
      belonging to the BI-1 family, we found that Growth-hormone inducible
      transmembrane protein (Ghitm) is another prospective member of the BI-1 family.
      Here we characterise Ghitm in a first analysis regarding its phylogeny,
      expression in cancer cell lines, and proteomical properties.

PMID- 18071585
TI  - Adjuvant effect of anti-4-1BB mAb administration in adoptive T cell therapy of
      cancer.
AB  - Administration of anti-4-1BB mAb has been found to be a potent adjuvant when
      combined with other therapeutic approaches, e.g. chemotherapy, cytokine
      therapies, anti-OX40 therapy, and peptide or DC vaccines. However, the adjuvant
      effect of anti-4-1BB mAb administration in adoptive T cell therapy of cancer has
      not been fully evaluated. In this report, effector T cells were generated in
      vitro by anti-CD3/anti-CD28 activation of tumor-draining lymph node (TDLN) cells
      and used in an adoptive immunotherapy model. While T cells or anti-4-1BB alone
      showed no therapeutic efficacy in mice bearing macroscopic 10-day pulmonary
      metastases, T cells plus anti-4-1BB mediated significant tumor regression in an
      anti-4-1BB dose dependent manner. Mice bearing microscopic 3-day lung metastases
      treated with T cells alone demonstrated tumor regression which was significantly
      enhanced by anti-4-1BB administration. NK cell depletion abrogated the augmented
      therapeutic efficacy rendered by anti-4-1BB. Cell transfer between congenic hosts
      demonstrated that anti-4-1BB administration increased the survival of adoptively
      transferred TDLN cells. Using STAT4(-/-) mice, we found that modulated IFN gamma
      secretion in wt TDLN cells after anti-CD3/CD28/4-1BB activation in vitro was lost
      in similarly stimulated STAT4(-/-) TDLN cells. Additionally, anti-4-1BB
      administration failed to augment the therapeutic efficacy of T cell therapy in
      STAT4(-/-) mice. Together, these results indicate that administered anti-4-1BB
      mAb can serve as an effective adjuvant to augment the antitumor reactivity of
      adoptively transferred T cells by recruiting the host NK cells; increasing the
      persistence of infused effector T cells, and modulating the STAT4 molecular
      signaling pathway.

PMID- 18071588
TI  - Smad3 -signalling and Th2 cytokines in normal mouse airways and in a mouse model
      of asthma.
AB  - This study investigates the role of Smad3 signalling for the T-helper2 (Th2)
      cytokine homeostasis in normal lungs and in a mouse model of asthma. We used mice
      deficient for Smad3, a central part of the major signal transduction pathway for
      TGF-beta and other related cytokines, and a mouse model for allergic asthma with
      ovalbumin (OVA) as the antigen. Compared to wild type mice, naive (unmanipulated)
      Smad3-/- mice exhibited significantly increased levels of proinflammatory
      cytokines and IL-4 as well as the Th2 associated transcription factor GATA-3 in
      the lung tissue and bronchoalveolar lavage (BAL). In the asthma model, mucin
      secretion and airway hyperresponsiveness (AHR) after allergen exposure was
      significantly increased in the Smad3-/- mice as compared to wild type (WT) mice.
      IL-4 levels in Smad3-/- were similar to those encountered in WT mice but IL-13
      levels were decreased in the airways of OVA sensitized Smad3-/- mice compared to
      corresponding WT mice. The results indicate that a lack of Smad3 dependent
      signalling in the normal state will lead to an increase in the GATA-3 levels and
      as a result of this the levels of IL-4 increase. However, the lack of Smad3 also
      seems to inhibit expression of some cytokines, especially IL-13. Our results also
      indicate that in the inflammatory state TGF-beta or related cytokines functions
      to counterbalance the effects of IL-4 rather than to critically regulate its
      expression.

PMID- 18071589
TI  - Concerted transcriptional regulation by BRCA1 and COBRA1 in breast cancer cells.
AB  - Cofactor of BRCA1 (COBRA1) was first identified as a protein that binds to the
      breast cancer susceptibility gene product BRCA1. COBRA1 modulates estrogen
      dependent and independent transcription and suppresses the growth of breast
      cancer cells. Its expression is significantly reduced in metastatic and recurrent
      breast cancer, pointing to a tumor suppressor function in breast cancer
      development. In light of these initial implications of COBRA1 in human breast
      cancer, the current investigation sought to obtain more direct functional
      evidence that links COBRA1 with BRCA1 in transcriptional regulation in breast
      cancer cells. Small hairpin RNA (shRNA)-mediated gene knockdown and gene
      expression microarray were used to study the impact of COBRA1 and BRCA1 on global
      transcription in the same breast cancer cell background. The gene expression
      profiling study in tissue culture cells uncovers a significant overlap of COBRA1-
      and BRCA1-regulated genes, many of which have been previously implicated in
      breast cancer progression. The data shown herein support the notion that COBRA1
      and BRCA1 may engage in common gene regulatory pathways to suppress breast cancer
      progression.

PMID- 18071590
TI  - A biomimetic approach to some specifically functionalized cyclic terpenoids.
AB  - The paper relates on the current advancements in the synthesis of complex cyclic
      terpenoids by superacidic induced cyclization of open chain precursors. It is
      shown that functional groups disposal in the initial substrate strongly
      influences the reaction outcome. Possible variations of the investigated compound
      structures include particularly alpha-functionalization and alpha,omega
      bifunctionalization. This approach allowed a selective initiation of cyclization
      sequence from an internal double bond or suspending the ring closure cascade to
      partially cyclized compounds. The reported synthetic schemes are attempts to
      mimic the biogenetical processes postulated in the living systems.

PMID- 18071591
TI  - Synthesis of a quaternary polyprenyl ammonium salt.
AB  - Reaction of primary C(55)-allylic alcohol moraprenol (WT(3)C(7-9)-OH, a
      polyprenol from mulberry leaves) with triethylamine in the presence of phosphorus
      oxychloride leads to a quaternary ammonium chloride with a good yield (72%) and
      high cis-stereoselectivity of the terminal isoprene unit. Cationic polyprenyl
      derivatives may be useful for transfection and immunological studies.

PMID- 18071592
TI  - How do we encourage clinician scientists in Singapore?

PMID- 18071593
TI  - Some milestones: specialist education, training and assessment in Singapore.
AB  - Singapore had its most significant milestone in 1905 when the Singapore Medical
      School was founded. The Academy of Medicine, founded in 1957, celebrates its
      Golden Anniversary in 2007. Thus, the events that influenced the development of
      postgraduate medicine, specialist education, training and examinations commenced
      rightly from 1957. These are presented chronologically. The significant roles
      played by the Academy, the University's Medical School and the Ministry of Health
      are highlighted, bearing in mind the ongoing developments in Singapore and
      globally over the years. To keep pace with the further developments and advances,
      the high gold standards in specialist training and assessment need to be refined
      with time. This can only be to the benefit of our patients and the community in
      Singapore and beyond.

PMID- 18071594
TI  - The role of electrophysiology in the diagnosis and management of cervical
      spondylotic myelopathy.
AB  - BACKGROUND: Cervical spondylotic myelopathy (CSM) is managed by conservative or
      surgical measures. While surgery is often performed in cases of longstanding or
      severe CSM, there is a lack of evidence concerning its efficacy. Transcranial
      magnetic stimulation (TMS) is a quick, safe, painless and non-invasive technique
      to study conduction in the descending corticospinal pathways in the spinal cord.
      The conduction time from the motor cortex to the anterior horn cell [central
      motor conduction time (CMCT)] is a measure of the integrity of corticospinal
      pathways. We have previously established the role of TMS in diagnosis and
      screening of CSM. In this study, we further investigate the use MEPs obtained
      with TMS in the outcome prediction of severe CSM patients requiring operative
      intervention. METHODS: We prospectively evaluated 46 consecutive patients (mean
      age, 57.6 years; range, 36 to 84 years; 28 men) presenting with clinical features
      of CSM over a 2-year period. Disease duration ranged from 6 to 24 months. A total
      of 45 healthy controls were studied for comparison. All patients underwent
      clinical scoring. Patients' initial clinical score (S1) and postoperative scoring
      at 6 months (S2) were based on a modified Japan Orthopedic Association Scoring
      Scale. A Modified Recovery Rate (MRR) was calculated based on the formula: (S2 -
      S1/17 - S1) x 100. We regarded a good surgical outcome as MRR of 50 or above.
      This was depicted as MRR50. The patients were separated into 4 groups according
      to the degree of cord compression by degenerative osteo-cartilaginous elements at
      the most significant level on MRI. TMS studies were performed before surgery.
      Each investigator was blinded to the results of the other investigators. RESULTS:
      The upper limb (UL) CMCT (r = -0.507, P <0.0005) and lower limb (LL) CMCT (r = -
      0.452, P = 0.002) were significantly and negatively correlated with S1.
      Similarly, UL MEP amplitude (r = 0.494, P <0005) and LL MEP amplitude (r = 0.305,
      P = 0.039) were significantly correlated with S1. Surgery consisted of anterior
      or posterior decompression with cervical laminoplasty, performed by an
      experienced team of orthopaedic surgeons. No significant intraoperative or
      postoperative complications were documented. Surgery resulted in significantly
      improved clinical scoring (unpaired t test, P <0.0005). No correlation between
      clinical scoring with patients' age, disease duration, severity or levels of cord
      compression on MRI was found. ULCMCT and MEP amplitude abnormality were
      significantly associated with improvement in clinical scoring after surgery (Mann
      Whitney test, P <0.05). The UL CMCT was the independent predictor of a good
      clinical outcome after surgery (odds ratio, 9.09; P = 0.011). CONCLUSIONS: In
      early CSM, lateral corticospinal tracts are first to be affected. It is thus
      possible that UL CMCT abnormality reflect more severe affectation of the
      corticospinal tracts placed relatively more medially in the cervical cord.
      Surgical intervention may have then effectively relieved the clinically
      significant compression, leading to a better outcome. This was further
      corroborated by our finding of negative correlation of S1 with UL CMCT,
      suggesting that patients who were clinically more severe were also
      electrophysiologically more abnormal, and subsequently benefited more from
      surgical decompression relative to patients with normal UL CMCT. This the largest
      series, to our knowledge, showing for the first time that UL CMCT abnormality
      obtained with TMS is an independent predictor of good surgical outcome in severe
      CSM.

PMID- 18071595
TI  - Recertification in internal medicine - the American experience.
AB  - The American Board of Internal Medicine (ABIM) sets standards and certifies and
      recertifies physicians to practise internal medicine and its subspecialties in
      America. The ABIM was established in 1936 as a non-profit corporation, one of
      many specialty boards, such as the American Board of Family Medicine, the
      American Board of Pediatrics, the American Board of Surgery, etc. The umbrella
      organisation for these groups is the American Board of Medical Specialties.
      Members of the American College of Physicians take certifying and recertifying
      examinations produced by ABIM. Beginning in 1990, ABIM certificates were valid
      for 10 years. To maintain certification, physicians were required to participate
      in ABIM maintenance of certification (MOC) programme. The goals are to improve
      quality of care, to set standards for clinical competency, to foster continuing
      scholarship, and lead to medical quality improvement. The MOC programme involves
      verification of credentials, completion of self-evaluation, and completion of a
      secure exam. The self-evaluation component is the most complex and has been the
      most controversial due to the diversity of internal medicine careers and
      continued learning patterns. ABIM continually introduces new options for
      evaluation of practice performance. In addition to recertification in General
      Internal Medicine, ABIM has subspecialty examinations. MOC has been well received
      by professional organisations, but there are areas of controversy. It has been
      accepted as an important way for internists to assure quality of practice and
      currency of medical information.

PMID- 18071596
TI  - Child development programme in Singapore 1988 to 2007.
AB  - Early childhood intervention programmes can shift the odds toward more favourable
      outcomes in development, especially for children at risk. However, there is no
      quick fix in the world for early childhood interventions. Programmes that work
      are rarely simple, inexpensive, or easy to implement. Each country must decide
      its own model and strategies and develop its resources based on existing
      infrastructures. Since its independence to become a sovereign nation in 1965,
      Singapore has undergone significant socio-economic changes. The infant and under
      5 childhood mortality rates are among the lowest in the world. A number of "new
      morbidities" have been identified to pose major challenges to child health in the
      next decades. They are chronic medical illnesses, developmental disabilities,
      learning problems, injuries and neglect, behavioural disturbances and disorders,
      sequelae associated with unhealthy life-styles, and social and emotional
      disorders. The need for a comprehensive child development programme is therefore
      obvious. The main objectives are identification and treatment of children with
      developmental and behavioural problems so as to correct developmental
      dysfunctions, minimise the impact of a child's disability or of prevailing risk
      factors, strengthen families, and establish the foundations for subsequent
      development. A child development programme has evolved in Singapore over the last
      20 years. The programme is multi-disciplinary, community-based, family-focused,
      and child-centric, with partnership and integration between government and
      voluntary community organisations.

PMID- 18071597
TI  - Bone generation in the reconstruction of a critical size calvarial defect in an
      experimental model.
AB  - OBJECTIVE: This study was designed to investigate the optimal combination of
      known osteogenic biomaterials with shape conforming struts to achieve calvarial
      vault reconstruction, using a canine model. METHODS: Eighteen adolescent beagles
      were divided equally into 6 groups. A critical size defect of 6 x 2 cm traversed
      the sagittal suture. The biomaterials used for calvarial reconstruction were
      demineralised perforated bone matrix (DBM), recombinant human bone morphogenetic
      protein-2 (rhBMP2) and autogenous platelet-rich plasma (PRP). The struts used
      were cobalt chrome (metal) or resorbable plate. The groupings were as follows: 1)
      DBM + metal, 2) DBM + PRP + metal, 3) DBM + PRP + resorbable plate, 4) DBM +
      rhBMP2 + metal, 5) DBM + rhBMP2 + PRP + metal, and 6) DBM + rhBMP2 + resorbable
      plate. Animals were euthanised at 3 months post-surgery. There was no mortality
      or major complications. Analysis was performed macroscopically, histologically,
      and with computed tomography (CT). RESULTS: There was complete bony regeneration
      in the rhBMP2 groups only. Non-rhBMP2 groups had minimal bony ingrowth from the
      defect edges and on the dural surface, a finding confirmed by CT scan and
      histology. PRP did not enhance bone regeneration. Shape conformation was good
      with both metal and resorbable plate. CONCLUSION: rhBMP2 but not PRP accelerated
      calvarial regeneration in 3 months. The DBM in the rhBMP2 groups were substituted
      by new trabecular bone. Shape molding was good with both metal and resorbable
      plate.

PMID- 18071598
TI  - The impact of mainland mothers on the obstetric services of Hong Kong.

PMID- 18071603
TI  - Screening for vancomycin-resistant enterococci using stools sent for Clostridium
      difficile cytotoxin assay is effective: results of a survey of 300 Patients in a
      large Singapore Teaching Hospital.
AB  - INTRODUCTION: To assess the efficacy of screening stools sent for Clostridium
      difficile cytotoxin assay (CDTA) for surveillance of vancomycin-resistant
      enterococci (VRE). MATERIALS AND METHODS: From April to May 2005, all stools
      submitted for CDTA were also cultured for VRE using vancomycin containing culture
      media. Isolates were identified to species level and vancomycin resistance
      confirmed, followed by polymerase chain reaction (PCR) for detection of
      vancomycin resistance genes and DNA fingerprinting. Over 2 consecutive days
      during that period, stool specimens or rectal swabs were also obtained from all
      patients in high-risk units (haematology, oncology, renal and intensive care).
      Fifty-one patients in each group were compared in terms of VRE risk factors
      previously identified. RESULTS AND DISCUSSION: The prevalence of VRE in both
      groups was similar [3/204 (1.5%) in the CDTA arm and 1/97 (1.0%) in the high-risk
      arm; P = 1.0, Fisher's exact test]. Prevalence of risk factors for VRE
      colonisation, including age, duration of hospitalisation, exposure to
      antibiotics, exposure to surgical procedures, presence of malignancy and diabetes
      mellitus was similar in both groups (P > 0.05). Only renal failure (P < 0.05) was
      more common in the high-risk group. All 4 isolates of VRE identified were
      genetically distinct by variable number tandem repeat (VNTR) typing; 3 were
      Enterococcus faecium (2 with the vanB gene, 1 with vanA) and one E. faecalis.
      CONCLUSION: Less than 2% of our high-risk patients are VRE carriers. In-hospital
      VRE screening using stools sent for CDTA is a simple, reasonable surrogate for
      screening individual high-risk patients as the patient risk profile is similar
      and the yield comparable in a low-prevalence setting.

PMID- 18071604
TI  - Development of a core curriculum on tuberculosis control for Philippine medical
      schools.
AB  - INTRODUCTION: As of 2001, the Philippines ranks 7th among the world's 22
      countries with a heavy tuberculosis (TB) burden. As the country accelerates its
      campaign to control the global epidemic, the Philippine Tuberculosis Initiatives
      for the Private Sector (PhilTIPS) joined the efforts to combat it through the
      Directly Observed Treatment Short-course (DOTS) strategy and brought it to the
      level of medical schools. PhilTIPS commissioned this work to develop an evidence
      based medical curriculum with strong and conscious integration of TB-DOTS.
      MATERIALS AND METHODS: In the needs assessment, curricula, sample tests, and
      syllabi were reviewed. Deans and curriculum committee chairs were also asked to
      answer a questionnaire dealing with how TB, TB control and DOTS were taught.
      Based on the needs assessment, the TB control-DOTS core curriculum was developed.
      Ten months after its implementation, a monitoring evaluation was conducted
      through questionnaires, review of records and key informant interviews.
      DISCUSSION: Representative samples of 18 out of 32 schools participated in the
      needs assessment and monitoring phase. Data revealed that the biomedical and
      clinical aspects of TB are emphasised in all schools. But only 7 out of 18
      (38.89%) actually dealt with DOTS. A competency-based, integrated, and
      interactive TB-DOTS curriculum was then developed. The competencies around which
      the curriculum was designed were: (1) a thorough understanding of TB as a
      biomedical and social phenomenon; (2) the management of TB patients; and (3) an
      adherence to DOTS in managing TB patients. The curriculum was reviewed by local
      and international panelists, and implemented in 2003 to 2004. Monitoring
      evaluation 10 months later revealed that this curriculum was minimally to
      moderately integrated by medical schools. The study exhorts all medical schools
      to empower their graduates with competence in TB-DOTS.

PMID- 18071605
TI  - Molecular analysis of the SMN1 and NAIP genes in Iranian patients with spinal
      muscular atrophy.
AB  - INTRODUCTION: Childhood-onset proximal spinal muscular atrophies (SMAs) are an
      autosomal recessive, clinically heterogeneous group of neuropathies characterised
      by the selective degeneration of anterior horn cells. SMA has an estimated
      incidence of 1 in 10,000 live births. The causative genes are survival motor
      neuron (SMN) gene and neuronal apoptosis inhibitory protein (NAIP) gene.
      Deletions of the telomeric copy of SMN gene (SMN1) have been reported in 88.5% to
      95% of SMA cases, whereas the deletion rate for NAIP gene (NAIP) is between 20%
      and 50% depending on the disease severity. The main objective of this study was
      to genetically characterise the childhood onset of SMA in Iran. MATERIALS AND
      METHODS: Molecular analysis was performed on a total of 75 patients with a
      clinical diagnosis of SMA. In addition to common PCR analysis for SMN1 exons 7
      and 8, we analysed NAIP exons 4 and 5, along with exon 13, as a internal control,
      by bi-plex PCR. RESULTS: The homozygous-deletion frequency rate for the telomeric
      copy of SMN exons 7 and 8 in all types of SMA was 97%. Moreover, exons 5 and 6 of
      NAIP gene were deleted in approximately 83% of all SMA types. Three deletion
      haplotypes were constructed by using SMN and NAIP genotypes. Haplotype A, in
      which both genes are deleted, was seen in approximately 83% of SMA types I and II
      but not type III. It was also found predominantly in phenotypically severe group
      with an early age of onset (i.e., less than 6-month-old). We also report 34 of
      our prenatal diagnosis. CONCLUSIONS: To our knowledge, the present study is the
      first one giving detailed information on SMN and NAIP deletion rates in Iranian
      SMA patients. Our results show that the frequency of SMN1 homozygous deletions in
      Iran is in agreement with previous studies in other countries. The molecular
      analysis of SMA-related gene deletion/s will be a useful tool for pre- and
      postnatal diagnostic.

PMID- 18071606
TI  - The role of topical traditional chinese medicaments as contact sensitisers in
      chronic venous leg ulcer patients.
AB  - INTRODUCTION: Leg ulcers are a chronic condition affecting the older population.
      In Singapore, the use of topical traditional Chinese medicaments (TTCM) is common
      amongst those older than 65 years of age. We study the role of TTCM as contact
      sensitisers in patients with chronic venous leg ulcers and its impact in the
      clinical management of these patients. MATERIALS AND METHODS: Patients with
      chronic leg ulcers attending the Wound and Ulcer Clinic at the National Skin
      Centre (NSC) between October 2005 and April 2006 were patch-tested to the NSC
      TTCM series. They were also patch-tested for other allergens from the NSC
      Standard Series, Medicament Series, Steroid Series and wound dressings. RESULTS:
      A total of 44 patients were patch-tested. Seventeen of the 44 (38.7%) patients
      were using or had used at least 1 TTCM. Seven patients (15.9%) had at least 1
      positive patch test (PT) reading to TTCM, giving a sensitisation rate of 41% (7
      of 17). A significantly high proportion of the patients, 94.1% (16 of 17) with a
      positive history of TTCM usage had at least 1 positive PT reading compared to
      those without a history of TTCM usage, 45.8% (11 of 24). CONCLUSION: TTCM play an
      important role as contact sensitisers in our patients with chronic venous leg
      ulcers and may be a significant factor in non- or poor-healing leg ulcers. In
      such patients, a history of TTCM usage should be sought for and patch testing
      should include the commonly used TTCM where relevant.

PMID- 18071607
TI  - Late complications following tetralogy of Fallot repair: the need for long-term
      follow-up.
AB  - INTRODUCTION: We report a series of operated tetralogy of Fallot (TOF) patients
      focusing on complications and outcomes. MATERIALS AND METHODS: Data from TOF
      patients seen at our centre's adult congenital heart disease clinic was analysed.
      RESULTS: There were 21 patients: the mean age was 32.2 +/- 12.4 years; the age at
      first operation was 9.0 +/- 7.9 years; the mean postoperative follow-up duration
      was 23.5 +/- 12.1 years; and the current New York Heart Association (NYHA)
      status: I, 82%; II, 4%; III, 14%. Fourteen patients had complete operative notes.
      All these patients underwent total TOF correction; 2 had staged aortopulmonary
      shunt with total correction at a mean of 3.2 years later, pulmonary artery patch
      augmentation in 8 patients and pulmonary valvotomy in 8 patients. Three patients
      required pulmonary valve homograft replacement for severe pulmonary regurgitation
      (PR) at 13, 28 and 36 years after the initial corrective operation. CURRENT
      INVESTIGATIONS: RBBB on ECG (91%), QRS duration 137 +/- 29 ms. Echocardiography
      showed dilated right ventricular end-diastolic (RVED) diameters (3.2 +/- 0.8 cm);
      severe PR (67%), residual right ventricular outflow tract obstruction (RVOTO)
      (42%) and VSD patch leakage (9%). Cardiac magnetic resonance (CMR) (8 patients)
      showed dilated RVED volumes 252.6 +/- 93.8 mL, indexed RV volume 165.7 +/- 34.8
      mL; RV systolic function was preserved in most patients with a RV ejection
      fraction of 49.5 +/- 5.7%. One patient had atrial tachycardia and another had
      frequent non-sustained ventricular tachycardia that required radiofrequency
      ablation. CONCLUSION: Patients with TOF who had full corrective surgery during
      childhood are now surviving into adulthood. Many challenges arising from
      complications in the postoperative period remain. It is imperative that adult TOF
      patients should have regular followup to monitor development and subsequent
      management of these complications.

PMID- 18071608
TI  - EUS-FNA of the left adrenal gland is safe and useful.
AB  - INTRODUCTION: There are limited data on the use of endosonography-guided fine
      needle aspiration (EUS-FNA) to determine the nature of left adrenal lesions. We
      described our experience in performing EUS-FNA of left adrenal lesions. CLINICAL
      PICTURE: During a 20-week period, data on consecutive patients who underwent EUS
      with or without EUS-FNA were prospectively captured. Patients with a left adrenal
      mass and who underwent EUS-FNA formed our study population. TREATMENT: EUS-FNA.
      OUTCOME: A total of 119 consecutive patients underwent diagnostic EUS +/- FNA,
      during which the left adrenal gland was routinely examined. Twelve of these
      patients underwent EUS as part of lung cancer staging and among these 12 lung
      cancer patients, 2 had left adrenal masses detected by computed tomography (CT).
      EUS detected left adrenal nodules in 2 other patients which were not visualised
      by CT. The overall prevalence of a left adrenal mass was 3.4%; in the subgroup
      with confirmed lung cancer, the prevalence was 33.3%. All 4 patients were male,
      with a mean age of 76.3 years (range, 67 to 87). The mean size of the left
      adrenal lesion was 30.4 mm (range, 9 to 84.8). EUS-FNA of the left adrenal
      lesions was performed under Doppler guidance. The mean number of needle passes
      was 2 (range, 1 to 4). A cellular aspirate was obtained in all patients. No
      procedural complications occurred. Metastatic non-small cell lung cancer was
      diagnosed in 2 patients, including a lesion missed on CT. For the other 2 cases,
      EUS-FNA revealed benign adrenal cells. CONCLUSIONS: EUS-FNA appears safe and
      useful for the evaluation of left adrenal masses.

PMID- 18071609
TI  - Sociodemographic factors influencing the effectiveness of public health education
      - a comparison of two studies in Singapore.
AB  - INTRODUCTION: We aimed to evaluate if sociodemographic factors influenced the
      effectiveness of public education programmes in Singapore. MATERIALS AND METHODS:
      Data were extracted from 2 independent cross-sectional studies that assessed the
      effectiveness of diabetes and HIV/ AIDS public health education programmes. The
      influence of sociodemographic factors including age, gender, ethnicity and years
      of education on diabetes and HIV/AIDS knowledge scores (surrogate marker for
      programme effectiveness) were assessed using separate univariable and multiple
      linear regression models for each outcome variable. RESULTS: A total of 1321
      subjects [46% male, mean (SD) age: 33.9 (13.44) years] participated in the
      diabetes study while 400 subjects [44% male, mean (SD) age: 33.9 (13.44) years]
      participated in the HIV/AIDS study. In univariable analyses, age, years of
      education and ethnicity influenced both diabetes and HIV/ AIDS knowledge scores.
      However, in multiple linear regression analyses, only age and years of education
      influenced both diabetes and HIV/AIDS knowledge scores. CONCLUSION: We found that
      age and years of education influenced the effectiveness of public health
      education, suggesting that there is a need to tailor public health education
      programmes to meet the needs of younger subjects and those with fewer years of
      education. That knowledge scores were similar between male and female subjects
      was surprising but could potentially be explained by equal access to information,
      high availability of information technology and heightened awareness of HIV/AIDS
      in Singapore.

PMID- 18071610
TI  - Should beta-blockers still be used as initial antihypertensive agents in
      uncomplicated hypertension?
AB  - Beta-blockers have long being used as first-line therapy for hypertension as
      their use had resulted in a reduction in cardiovascular morbidity and mortality
      in controlled clinical trials. A recent meta-analysis comparing beta-blockers to
      all other anti-hypertensive drugs taken together has found that stroke reduction
      was sub-optimal. Specifically, atenolol was associated with a 26% higher risk of
      stroke compared with other drugs. Several reasons may explain the less favourable
      outcomes with beta-blocker therapy. These include some adverse metabolic
      abnormalities such as dyslipidaemia and new-onset diabetes, and less effective
      reduction of central aortic compared with brachial blood pressure. Newer beta
      blockers such as carvedilol or nebivolol are better tolerated. These beta
      blockers have a vasodilating effect, which may beneficially affect systolic blood
      pressure in the aorta. Their long-term cardiovascular outcome in hypertension is
      still not known. Further studies would be required to show that stroke is
      adequately reduced by these newer beta-blockers. In conclusion, beta-blockers
      should not be the first drugs of choice in the management of uncomplicated
      hypertension. They may be used in addition to other antihypertensive agents to
      achieve blood pressure goals. However, in patients with angina pectoris, a
      previous myocardial infarction, heart failure and certain dysrhythmias, beta
      blockers still play an important role.

PMID- 18071611
TI  - Linking anthropological analysis and epidemiological evidence: formulating a
      narrative of HIV transmission in Acholiland of northern Uganda.
AB  - For twenty years, a region of northern Uganda known as Acholiland has been
      heavily affected by war, leading to the formation of internally displaced
      people's camps, rape, transactional sex and child abductions. While it is clear
      that the war has had onerous consequences for the health of the Acholi people,
      the specific impact of the war on HIV transmission remains unclear, as the
      epidemiological evidence presents an ambiguous picture of HIV prevalence
      patterns. Other than a few non-governmental organization reports, very little
      qualitative data exists about the impact of HIV on the Acholi population.
      Attempting to formulate a clearer narrative of HIV transmission in Acholiland,
      this paper jointly analyses the historical and political context of the Acholi
      people and the war, the epidemiologic evidence of HIV prevalence patterns, and
      the ethnographic perspectives of Acholi healthcare workers and patients living
      with HIV/AIDS. Juxtaposing these sources of information allows for the emergence
      of a rich understanding of HIV in Acholiland. It is argued that three specific
      forms of violence--physical, symbolic and structural--create vulnerability to HIV
      infection in Acholiland, although to variable degrees dependent on location. The
      ethnographic evidence presented regarding HIV's impact on Acholiland suggests
      that an incorporation of historical, political, cultural and social factors must
      form the backbone of efforts both to understand HIV transmission and design
      strategies for curbing the epidemic in war settings.

PMID- 18071612
TI  - Widowhood in the era of HIV/AIDS: a case study of Slaya District, Kenya.
AB  - Luo women are believed to acquire contagious cultural impurity after the death of
      their husbands that is perceived as dangerous to other people. To neutralise this
      impure state, a sexual cleansing rite is observed. In the indigenous setting, the
      ritual was observed by a brother-in-law or cousin of the deceased husband through
      a guardianship institution. However, with the emergence of HIV/AIDS, many
      educated brothers-in-law refrain from the practice and instead hire professional
      cleansers as substitutes. If the deceased spouses were HIV positive, the ritual
      places professional cleansers at risk of infection. Thereafter, they could act as
      a bridge for HIV/AIDS transmission to other widows and to the general population.
      This paper provides insights into reasons for continuity of widowhood rites in
      Siaya District. Twelve focus group discussions and 20 in-depth interviews were
      conducted. The cultural violence against Luo widows could spread HIV/AIDS, but
      Christianity and condoms act as coping mechanisms.

PMID- 18071613
TI  - Understanding and measuring AIDS-related stigma in health care settings: a
      developing country perspective.
AB  - AIDS-related stigma and discrimination remain pervasive problems in health care
      institutions worldwide. This paper reports on stigma-related baseline findings
      from a study in New Delhi, India to evaluate the impact of a stigma-reduction
      intervention in three large hospitals. Data were collected via in-depth
      interviews with hospital staff and HIV-infected patients, surveys with hospital
      workers (884 doctors, nurses and ward staff) and observations of hospital
      practices. Interview findings highlighted drivers and manifestations of stigma
      that are important to address, and that are likely to have wider relevance for
      other developing country health care settings. These clustered around attitudes
      towards hospital practices, such as informing family members of a patient's HIV
      status without his/her consent, burning the linen of HIV-infected patients,
      charging HIV-infected patients for the cost of infection control supplies, and
      the use of gloves only with HIV-infected patients. These findings informed the
      development and evaluation of a culturally appropriate index to measure stigma in
      this setting. Baseline findings indicate that the stigma index is sufficiently
      reliable (alpha = 0.74). Higher scores on the stigma index--which focuses on
      attitudes towards HIV-infected persons--were associated with incorrect knowledge
      about HIV transmission and discriminatory practices. Stigma scores also varied by
      type of health care providers--physicians reported the least stigmatising
      attitudes as compared to nursing and ward staff in the hospitals. The study
      findings highlight issues particular to the health care sector in limited
      resource settings. To be successful, stigma-reduction interventions, and the
      measures used to assess changes, need to take into account the sociocultural and
      economic context within which stigma occurs.

PMID- 18071614
TI  - Food insecurity, HIV/AIDS pandemic and sexual behaviour of female commercial sex
      workers in Lagos metropolis, Nigeria.
AB  - This study examined the role of hunger and food insecurity in the sexual
      behaviour of female commercial sex workers in Lagos metropolis, Nigeria within
      the context of HIV/AIDS. In addition, the study investigated the prevalence of
      sexually transmitted infections (STIs) and induced abortion among the
      respondents. Cross-sectional survey and in-depth interview research methods were
      adopted to generate both quantitative and qualitative data from the respondents.
      Findings of the study showed that 35.0% of the respondents joined the sex
      industry because of poverty and lack of other means of getting daily food. While
      all the respondents had knowledge about the existence of HIV/AIDS, 82.0% of them
      identified sexual intercourse as a major route of HIV transmission. There was a
      significant relationship between poverty, food insecurity and consistent use of
      condoms by female sex workers at P<0.01. Specifically, only 24.7% of the
      respondents used condoms regularly in every sexual act. Consequently, 51.6% had
      previous cases of STIs. The most prevalent STI among the respondents was
      gonorrhea, with 76.4% prevalence among ever infected female sex workers. This was
      followed by syphilis with a prevalence of 21.1%. In addition, 59.1% of the sample
      had become pregnant while on the job and 93.1% of these pregnancies were aborted
      through induced abortion. In conclusion, hunger and malnutrition were the factors
      that pushed young women into prostitution in Nigeria and these same factors
      hindered them from practicing safe sex within the sex industry. Thus, it is
      recommended that the Nigerian government should develop programmes that will
      reduce hunger and food insecurity, in order to reduce rapid transmission of HIV
      infection in the country.

PMID- 18071615
TI  - Knowledge about HIV/AIDS and policy knowledge in a South African state hospital.

PMID- 18071616
TI  - Report and policy brief from the 4th Africa Conference on Social Aspects of
      HIV/AIDS Research: innovations in access to prevention, treatment and care in
      HIV/AIDS, Kisumu, Kenya, 29 April - 3 May 2007.
AB  - About 520 delegates from all over Africa and 21 countries attended the
      conference. This report and policy brief summarises the key findings and
      suggested policy options that emerged from rapporteur reports of conference
      proceedings including the following themes: (1) Orphans and vulnerable children,
      (2) Treatment, (3) Prevention, (4) Gender and male involvement, (5) Male
      circumcision, (6) People living with HIV/AIDS, (7) Food and nutrition, (8)
      Socioeconomics, and (9) Politics/policy. Two (11.8%) of the 17 OVC projects from
      the three countries were classified as best practice interventions. Of the 83
      abstracts that were accepted at the conference, only 7 (8.4%) were dealing with
      antiretroviral therapy (ART). There has been tremendous effort by various
      organisations to provide information about prevention of HIV/AIDS. Information
      received by adolescents has been effective in increasing their knowledge, but
      without positive sexual behaviour change. The conference noted the contribution
      of gender discrimination and violence to the HIV epidemic and the different risks
      that men and women face in relation to the epidemic. Social scientists need to
      study the deep cultural meanings attached to male circumcision among different
      ethnic groups to be able to guide the debate on the latest biomedical findings on
      the protective effect of circumcision against HIV. Palliative care and support is
      crucial for coping among people living with HIV/AIDS (PLWHA) in order to deal
      with medical and psychological issues. Results from several countries have helped
      researchers to explore alternative ways of examining poverty in the context of
      HIV and AIDS. Policy frameworks which are likely to succeed in combating HIV/AIDS
      need to be updated to cover issues of access, testing, disclosure and stigma. In
      general, the conference was successful in identifying innovations in access to
      prevention, treatment and care in HIV/AIDS.

PMID- 18071617
TI  - Results 1 year after the Reemex system was applied for the treatment of stress
      urinary incontinence caused by intrinsic sphincter deficiency.
AB  - We present 1-year results obtained with Reemex for the cure of intrinsic
      sphincter deficiencies (ISDs). We recruited all patients with primary cases of
      stress urinary incontinence (SUI) due to an ISD (Valsalva leak-point pressure
      less than 60 cm or maximal urethral closure pressure less than 20 cm) who did not
      receive previous surgery. Thirty-eight patients were operated on. Postoperative
      pain was 3 (range, 1-5, visual analogue scale) at 24 h from surgery. Immediate
      regulation (the day after surgery) was necessary in three of 38 patients (7.9%),
      two for obstructive voiding difficulties and one for incontinence. Late
      regulation was necessary in three of 38 patients (7.9%), two for obstructive
      voiding difficulties (after 6 months) and one for incontinence (1 year). Symptoms
      resolved after the sling adjustment. Our results suggest that sling adjustments
      resolve postoperative failures and maintain the success rate of the Reemex system
      even in the midterm.

PMID- 18071618
TI  - Sexual function in women before and after transvaginal mesh repair for pelvic
      organ prolapse.
AB  - The aim of the study was to assess sexual function in women before and after
      surgery with transvaginal mesh for pelvic organ prolapse. Women were invited to
      complete a sexual function questionnaire including the Lemack and the Pelvic
      Organ Prolapse Urinary Incontinence Sexual Questionnaires (PISQ-12) before
      undergoing surgery and 1 year after surgery. Eighty-three complete pre and
      postoperative questionnaires were analyzed. Mean age was 65.1 years. Forty-six
      were sexually inactive and 37 were sexually active women. Two sexually active
      women completed the preoperative PISQ-12 questionnaire retrospectively after
      surgery. There were no significant differences after surgery in the answers to
      the Lemack questionnaire and PISQ-12 scores. These results suggest that
      nonabsorbable transvaginal mesh repair of genital prolapse does not impair sexual
      function 1 year after surgery. Nevertheless, patients should not necessarily
      expect a significant improvement in sexual function outcome following
      transvaginal mesh repair for genital prolapse.

PMID- 18071619
TI  - Pregnancy and delivery after mid-urethral sling procedures for stress urinary
      incontinence: case reports and a review of literature.
AB  - In this article, the effects of pregnancy and delivery on the development of
      stress urinary incontinence are described with special emphasis on the
      obstetrical management in women who wish to become pregnant or are pregnant after
      a preceding mid-urethral sling procedure. Three case histories and a review of
      literature are presented. Pregnancy after a preceding incontinence operation is
      rare and makes it quite difficult to formulate guidelines about delivery when a
      pregnancy occurs. The best advice is to postpone incontinence surgery until after
      the last pregnancy. There is evidence that an elective caesarean delivery
      protects against stress urinary incontinence in case of pregnancy after bladder
      neck suspension. For mid-urethral sling procedures, this evidence is not
      available. The presented case reports do not clearly demonstrate that caesarean
      delivery is necessary in case of pregnancy and delivery after a mid-urethral
      sling procedure. Furthermore, a second mid-urethral sling operation is a minor
      procedure compared to a caesarean section, and there is evidence that a second
      mid-urethral sling operation has the same success rate as the first procedure.

PMID- 18071620
TI  - Cost-effective screening for urinary tract infections in urogynaecological
      patients.
AB  - This study aims to test the cost-effectiveness of reagent-strip urine nitrite
      compared with microbiological laboratory testing for screening of urinary tract
      infections (UTI). The study is a retrospective review of 708 female patients who
      underwent cystometry during a 1-year period. Urine dipstick nitrite was used as a
      screening test for UTI while urine cultures were taken as an outcome. Symptoms of
      UTI were noted. Of 708 patients screened, 70 (9.9%) had a significant UTI. Only
      32 (4.5%)of 708 patients were nitrite positive. Urine dipstick nitrite has
      sensitivity of 40%, specificity of 99%, positive predictive value (PPV) of 88 %
      and negative predictive value (NPV) of 94%. If the screening test included
      symptoms for UTI together with urine nitrite, the results are: sensitivity 89%,
      specificity 31%, PPV 12% and NPV 96%. A combination of screening with urine
      nitrite and UTI symptoms can increase sensitivity to 89%. A total of 29% of
      specimens (screen negative=nitrite negative/asymptomatic) can then be excluded
      from UFEME/culture testing, thus resulting in cost savings.

PMID- 18071621
TI  - A copia-like retrotransposon gene encoding gypsy-like integrase in a red alga,
      Porphyra yezoensis.
AB  - A genomic PCR fragment of 4581 bp, referred to as PyRE10G, was isolated from the
      red alga Porphyra yezoensis. PyRE10G contained a putative open reading frame
      encoding gag, protease, integrase, reverse transcriptase (RT), and RNase H, but
      one stop codon was present in the integrase region. Southern blot analysis
      revealed that PyRE10G exists as a single copy in the genome. From the order of
      gene arrangement of polyproteins, PyRE10G appears to be a copia-like
      retrotransposon. Amino acid sequences of PyRE10G RT and RNase H were closely
      related to those of copia-like retrotransposons. In contrast, the phylogenetic
      tree suggested that PyRE10G integrase stands within the gypsy elements and
      outside the copia group. PyRE10G is the first example of a chimeric composition
      of copia- and gypsy-like polyprotein genes in a single element, supporting the
      hypothesis that long terminal repeat-containing retrotransposons have evolved by
      fusion of ancestral RT/RNase H and other polyprotein genes.

PMID- 18071622
TI  - Large patent median arteries and their relation to the superficial palmar arch
      with respect to history, size consideration and clinic consequences.
AB  - BACKGROUND: A large patent median artery can be involved in several clinical
      disorders like carpal tunnel syndrome, anterior interosseous nerve syndrome and
      pronator syndrome. METHODS: The frequency and variability in the expression of
      the median artery and the expression of the other forearm arteries were recorded
      during two dissection courses. The topography of the arteries with their
      ramifications was documented on diagrams and photographs. The outer diameters of
      forearm arteries were measured. RESULTS: A large median artery was found in 4 of
      54 arms (7.4%). The median arteries took their origin from the ulnar artery or
      the common interosseous artery. In one case, the median artery pierced the median
      nerve in its course under the pronator teres. The outer diameters of the median
      arteries varied between 1.5 and 2.0 mm proximally and 1.5 and 2.0 mm distally.
      The diameters of the radial arteries varied between 3.0 and 5.5 mm proximally and
      3.0 and 4.0 mm distally and were not reduced in any of the four cases with a
      large median artery. CONCLUSIONS: Surgeons should be aware of other variations in
      the forearm when a persistent median artery is identified, for example high
      median nerve bifurcations. Furthermore, it should be kept in mind that additional
      structures leading to nerve compression may be present in the carpal tunnel.

PMID- 18071623
TI  - Compartmental anatomy of the superficial fibular nerve with an emphasis on
      fascial release operations of the leg.
AB  - Compartment syndrome is a common cause of lower extremity pain via an increased
      intra-compartmental pressure. Fasciotomy is currently the mainstay for surgical
      treatment. Fasciotomy can be performed either with classical open or minimally
      invasive techniques including endoscopically assisted or semi blind subcutaneous
      releases. Incompletely released fascial compartments, soft tissue damage, and
      neurovascular injury, which includes superficial fibular nerve injury are common
      complications. The aim of this study was to investigate the localization of the
      superficial fibular nerve (SFN) in the lateral and the anterior compartments.
      Thirty-eight legs of 20 cadavers fixed in 10% formaldehyde were dissected and the
      compartmental anatomy of the SFN investigated. Three particular types in the
      course of SFN were determined. In 71% of the cases, the SFN coursed entirely
      within the lateral compartment of the leg (Type I). In 23.7%, the SFN penetrated
      the anterior intermuscular septum, 12.7 cm inferior to the apex of the head of
      fibula and coursed in the anterior compartment (Type II). In the remaining 5.3%
      of the specimens the SFN had branches both in the anterior and lateral
      compartments (Type III). Knowledge of variations of the SFN with reference to
      compartmental anatomy of the leg may be useful in fascial release operations.

PMID- 18071624
TI  - Survival after transcoronary ablation of septal hypertrophy in hypertrophic
      obstructive cardiomyopathy (TASH): a 10 year experience.
AB  - BACKGROUND: Catheter-based treatment of patients with hypertrophic obstructive
      cardiomyopathy (HOCM) by alcohol ablation (transcoronary ablation of septal
      hypertrophy, TASH) leads to symptomatic and haemodynamic improvement. However,
      little is known regarding the survival and its evolution since the introduction
      of the method in 1995. Theoretically, the method may be harmful, because widening
      of the obstructed left ventricular outflow tract is achieved by a septal
      infarction and subsequently by a potentially arrhythmogenic scar. OBJECTIVE: This
      study sought to determine the impact of TASH on the survival of all patients with
      HOCM treated in our institution between 1995 and 2005. METHODS: Survival was
      assessed from the early beginning in each of 644 consecutive patients to April
      2005. Group A comprises a first series of 329 patients who were treated in a dose
      finding strategy with decreasing amounts of ethanol until December 2001, on
      average, from 2.9 ml to 0.93 ml/patient. The survival of this group was analysed
      using Kaplan-Meier estimates, multivariate Cox regression and Log-Rank testing.
      Group B comprises 315 patients of the following "low alcohol dose era" (mean
      amount of ethanol 0.8 +/- 0.4 ml, range 0.3-1.5 ml) and their mid-term survival
      (period to first regular 6-month post-procedural control). RESULTS: All patients
      (age 58 +/- 15 years, 99.2% follow up, mean 1.4 years): 33 patients died (5.1%
      all cause mortality), including perioperative deaths. 14/33 (42%) died from
      cardiac reasons. Annual total (all cause) mortality was 3.2%, total in-hospital
      mortality 1.2% in all patients (8 of 644 patients, 6 of them with severe
      comorbidity) and 0.4% in low risk patients. Annual cardiac mortality after
      hospital discharge was 0.7% (6 patients, all with sudden death). Group A (age 58
      +/- 15 years, 98.8% follow up, mean 2.1 years, maximum 6.2 years): 29 patients
      died (total annual mortality 4.3%), 10 of them from hypertrophic cardiomyopathy
      related reasons resulting in a total in-hospital mortality of 1.8% (6 deaths), a
      cardiac annual mortality of 1.5% (including hospital mortality) and 0.6%/year
      after hospital discharge. Age was identified as an independent predictor of
      increased overall mortality (P = 0.002) and lower alcohol dosage and the absence
      of atrial fibrillation as independent predictors of reduced cardiac mortality (P
      = 0.005 and P = 0.039, respectively). With focus on the median value of the
      alcohol quantity (2.0 ml), patients treated with high amounts (>2.0 ml) showed a
      higher total mortality than patients treated with small amounts (< or =2.0 ml) (P
      = 0.031) and alcohol turned out to be an independent predictor of survival (P =
      0.047). The same holds true for a homogenous subset of 262 patients with respect
      to cardiac mortality (P = 0.018). Group B (age 57 +/- 14 years, 99.7% follow up,
      mean 7.3 months): Total in-hospital mortality was 0.6% (2 of 315 patients; P =
      0.173, group A/B) and cardiac in-hospital mortality 0% (P = 0.016, group A/B).
      During follow up two patients died, both of them experienced a sudden death
      reflecting an annual mortality of 1.0%. CONCLUSION: These data represent the
      largest available database on survival after alcohol septal ablation of HOCM from
      a single centre with large experience, and its evolution over 10 years with
      increasing procedural experience including the pronounced reduction of ethanol
      quantity in a systematic doses finding strategy. The in-hospital mortality has
      become very low. Cardiac survival during follow up was excellent, however, the
      well-known risk of sudden death is not completely eliminated. Longer follow-up
      time would be desirable for definite evaluation of this relatively new
      therapeutic option in the management of HOCM.

PMID- 18071625
TI  - Kinematic analysis of facial behaviour in patients with schizophrenia under
      emotional stimulation by films with "Mr. Bean".
AB  - In schizophrenic patients, motor functioning is substantially disturbed.
      Kinematic analysis is useful in examining this motor dysfunction. Using kinematic
      analysis, we aimed to investigate facial movement in schizophrenic patients
      responding to humorous film stimuli ("Mr. Bean"). Ultrasound markers were
      attached to pre-defined facial points while subjects watched a funny film sketch.
      The study included 21 schizophrenic in-patients (13 men, 8 women; mean (S.D.)
      age: 32.1 (10.4) years) and 30 healthy individuals (12 men, 18 women; mean (S.D.)
      age: 35.7 (11.0) years). Unmedicated schizophrenic patients showed an abnormally
      high initial velocity of laughing (IV), while patients treated with typical
      neuroleptics demonstrated an abnormally low IV. There was a significant positive
      correlation between severity of negative symptoms and IV. Kinematical analysis of
      facial movement using IV could help to distinguish subclinical Parkinsonian
      syndromes induced by typical neuroleptics from negative symptoms of
      schizophrenia.

PMID- 18071626
TI  - Kinship, dispersal and hantavirus transmission in bank and common voles.
AB  - Hantaviruses are among the main emerging infectious agents in Europe. Their mode
      of transmission in natura is still not well known. In particular, social features
      and behaviours could be crucial for understanding the persistence and the spread
      of hantaviruses in rodent populations. Here, we investigated the importance of
      kinclustering and dispersal in hantavirus transmission by combining a fine-scale
      spatiotemporal survey (4 km2) and a population genetics approach. Two specific
      host-hantavirus systems were identified and monitored: the bank vole Myodes,
      earlier Clethrionomys glareolus--Puumala virus and the common vole Microtus
      arvalis--Tula virus. Sex, age and landscape characteristics significantly
      influenced the spatial distribution of infections in voles. The absence of
      temporal stability in the spatial distributions of viruses suggested that
      dispersal is likely to play a role in virus propagation. Analysing vole kinship
      from microsatellite markers, we found that infected voles were more closely
      related to each other than non-infected ones. Winter kin-clustering, shared
      colonies within matrilineages or delayed dispersal could explain this pattern.
      These two last results hold, whatever the host-hantavirus system considered. This
      supports the roles of relatedness and dispersal as general features for
      hantavirus transmission.

PMID- 18071627
TI  - Trends in meta-analysis of genetic association studies.
AB  - The number of published genetic association studies (GASs) is increasing
      tremendously due to the availability of mapped single-nucleotide polymorphisms
      (SNPs) and advances in genotyping technologies. A search in HuGENet illustrates
      the rapid accumulation of evidence for major diseases. Recently, there has been a
      lot of activity regarding genome-wide association studies (GWASs), and a growing
      number of forthcoming studies is expected. GASs and GWASs are usually
      underpowered to detect significant associations, and the varying quality of
      reporting publications befuddles researchers. A meta-analysis can increase power
      and provide standards of reporting results. However, the conduct of a meta
      analysis of GASs faces a major obstacle, which is the structure and diversity of
      stored information in databases. Similar problems are expected for GWASs, though
      the data are not yet publicly available. The development of a Web-based system
      for the detailed and structured recording of GAS or GWAS data, accompanied by an
      estimation of the overall genetic risk effects, would enable scientists to keep
      track of evidence for gene-disease associations.

PMID- 18071628
TI  - Optimized folding simulations of protein A.
AB  - We describe optimized parallel tempering simulations of the 46-residue B-fragment
      of protein A. Native-like configurations with a root-mean-square deviation of
      approximately 3 A to the experimentally determined structure (Protein Data Bank
      identifier 1BDD) are found. However, at biologically relevant temperatures such
      conformations appear with only approximately 10 % frequency in our simulations.
      Possible shortcomings in our energy function are discussed.

PMID- 18071629
TI  - Headache in a patient with Klinefelter's syndrome and hyperostosis frontalis
      interna.
AB  - Hyperostosis frontalis interna (HFI) has been reported in older women, but
      reports in men are rare. We present a novel case of migraine headache in a
      gentleman with Klinefelter's syndrome and HFI, along with a discussion of
      possible pathophysiologic mechanisms underlying both the headache and the HFI.

PMID- 18071630
TI  - Temporary confusion depending on the usage of naratriptan.
AB  - In this report, a case with vitamin B12 deficiency showing a temporary confusion
      depending on the usage of naratriptan during the migraine attack was presented.

PMID- 18071631
TI  - Helicobacter pylori infection as an environmental risk factor for migraine
      without aura.
AB  - Helicobacter pylori (H. pylori) infection has recently been associated with
      various extraintestinal pathologies and migraine. The aim of this study was to
      investigate the correlation of the H. pylori infection with the pathogenesis of
      migraine without aura, especially in cases not affected by endogenous risk
      factors, like hereditary pattern or hormonal fluctuations.A total of 49
      outpatients (37 females and 12 males; age range: 19-47 years; mean age: 31,+/-14
      years) affected by migraine without aura was evaluated. We divided them in 2
      subgroups: a) with positive familial history, and/or with menstrual type of
      migraine b) with negative familial history and with menstrual unrelated type of
      migraine. H. pylori infection was diagnosed by the 13 C- urea breath test (INFAI 
      test). Control subjects consisted of 51 patients without any primary headache
      history (38 females; mean age of 32,+/-14,4 years; range 21-49 years), who
      underwent upper gastrointestinal (GI) endoscopy for investigation of anaemia or
      non ulcer dyspepsia. H. pylori detection was based on the histologic analysis of
      gastric mucosa biopsy. The prevalence of H. pylori infection was significantly
      higher in the migraineurs without aura compared to controls (p=0.016). The
      prevalence of H. pylori infection was significantly high in the mixed and in the
      female group of our patients without other predisposing factors for migraine
      without aura (81 and 87% respectively), while in the same groups with
      predisposing factors (menstruation and/or family history) the prevalence was only
      36 and 37% respectively (p=0,001 for the first group and p=0,002 for the second
      group). Our results seem to highlight the role of H. pylori infection as a
      probable independent environmental risk factor for migraine without aura,
      especially in patients that are not genetically or hormonally susceptible to
      migraine.

PMID- 18071632
TI  - Frequency of spontaneous intracranial hypotension in the emergency department.
AB  - Spontaneous intracranial hypotension is considered a rare disorder. We conducted
      a study on the frequency of spontaneous intracranial hypotension in the emergency
      department (ED). We identified patients with spontaneous intracranial hypotension
      evaluated in the ED of a large urban hospital between 1 January 2003 and 31
      December 2006. For comparison, we also identified all patients with spontaneous
      subarachnoid haemorrhage (SAH). Eleven patients with previously undiagnosed
      spontaneous intracranial hypotension were evaluated in the ED during the four
      year time period. All patients presented with positional headaches and the
      duration of symptoms varied from one day to three months. None of the patients
      were correctly diagnosed with spontaneous intracranial hypotension in the ED.
      During the same time period, 23 patients with aneurysmal SAH were evaluated.
      Spontaneous intracranial hypotension is more common than previously appreciated
      and the diagnosis in the ED remains problematic.

PMID- 18071633
TI  - Murine leukemia P388 vinorelbine-resistant cell lines are sensitive to
      vinflunine.
AB  - The work presented here was initiated to explore the mechanisms underlying
      vinorelbine resistance in two previously established murine leukemia P388 cell
      lines (N.63 and N2.5). IC(50) measurements demonstrated that the vinorelbine
      resistant cell line N.63 was sensitive to both vinblastine and vinflunine. In
      addition, vinorelbine-resistant cell line N2.5 retained sensitivity to
      vinflunine. We used flow cytometry with propidium iodide to measure G2/M arrest
      in response to drug treatment. Annexin V labeling was used as a marker of
      apoptosis and JC-1 dye labeling as a marker of mitochondrial membrane
      depolarization to explore differential responses that might help explain the
      absence of cross resistance to vinflunine. At equipotent (10X IC(50)) doses,
      after 8 h of drug treatment, vinflunine induced G2/M arrest in a significantly
      larger fraction of vinorelbine- resistant cells compared to vinorelbine. At the
      same drug doses, at 16 h after initiation of drug treatment, vinflunine induced a
      statistically significant greater apoptotic response and mitochondrial
      depolarization. The mitochondrial depolarization at 16 h was confirmed by Western
      blotting that showed release of cytochrome c. Comparison of apoptotic and
      mitochondrial depolarization responses in vinorelbine-resistant cells upon
      exposure to vinorelbine, vinblastine and vinflunine demonstrated the following
      pattern of drug activity: vinflunine > vinblastine > vinorelbine, confirming the
      importance of a antimitotic-induced mitochondria-mediated pathways in these P388
      cell lines. We conclude that vinflunine may be preferred for treatment of
      specific cancers compared to other vinca alkaloids due to its enhanced effects on
      apoptotic pathways that follow G2/M arrest.

PMID- 18071634
TI  - Cytotoxic effects of curcumin on osteosarcoma cell lines.
AB  - Curcumin (diferuloylmethane), one of the main components of the Indian spice
      turmeric, is known to possess potent anti-inflammatory and anti-oxidant
      properties. In addition, curcumin has also been shown to have in vitro and in
      vivo efficacy against a variety of malignancies. In the current study we examined
      the cytotoxic effect of curcumin on seven osteosarcoma (OS) cell lines with
      varying degrees of in vivo metastatic potential. Curcumin inhibited the growth of
      all OS cell lines tested with half-maximal inhibitory concentration values
      ranging from 14.4 to 24.6 microM. Growth inhibition was associated with a dose
      dependent increase in the number of apoptotic cells and accumulation of cells in
      the G(2)/M phase of the cell cycle. Curcumin treatment also resulted in cleavage
      of caspase-3 and poly adenosine diphosphate-ribose polymerase. Moreover, curcumin
      treatment was associated with an increase in cellular levels of the apoptotic B
      cell leukemia/lymphoma 2 (Bcl-2)-associated X protein and a decrease in cellular
      content of the anti-apoptotic protein Bcl-2. In addition, curcumin treatment also
      inhibited the migration of OS cell lines. These data indicate that the potent
      cytotoxic activity of curcumin on OS cell lines is mediated by induction of
      apoptotic processes. Thus, curcumin has potential to be a novel OS
      chemotherapeutic agent.

PMID- 18071636
TI  - The bone microenvironment in metastasis; what is special about bone?
AB  - The skeleton is a common destination for many cancer metastases including breast
      and prostate cancer. There are many characteristics of bone that make it an ideal
      environment for cancer cell migration and colonization. Metaphyseal bone, found
      at the ends of long bone, in ribs, and in vertebrae, is comprised of trabecular
      bone interspersed with marrow and rich vasculature. The specialized
      microvasculature is adapted for the easy passage of cells in and out of the bone
      marrow. Moreover, the metasphyseal regions of bone are constantly undergoing
      remodeling, a process that releases growth factors from the matrix. Bone turnover
      also involves the production of numerous cytokines and chemokines that provide a
      means of communication between osteoblasts and osteoclasts, but co-incidentally
      can also attract and support metastatic cells. Once in the marrow, cancer cells
      can interact directly and indirectly with osteoblasts and osteclasts, as well as
      hematopoietic and stromal cells. Cancer cells secrete factors that affect the
      network of cells in the bone microenvironment as well as interact with other
      cytokines. Additionally, transient cells of the immune system may join the local
      mileau to ultimately support cancer cell growth. However, most metastasized cells
      that enter the bone marrow are transient; a few may remain in a dormant state for
      many years. Advances in understanding the bone cell-tumor cell interactions are
      key to controlling, if not preventing metastasis to bone.

PMID- 18071635
TI  - The role of [18F]-fluorodeoxyglucose positron emission tomography in predicting
      plexiform neurofibroma progression.
AB  - BACKGROUND: The role of FDG-PET for managing patients with plexiform
      neurofibromas (PN) is unclear. While many PN tumors exhibit periods of rapid
      growth, others grow slowly or unpredictably and may have periods of relative
      quiescence. The ability to predict which PN are likely to progress should
      facilitate a more timely initiation of medical treatments. Since conventional
      radiographic techniques have limited prognostic value, the use of a functional
      imaging modality to predict tumor progression is desirable. We hypothesized that
      PN tumors with high metabolic activity as demonstrated by FDG-PET are more likely
      to progress in the following year. METHODS: All patients were clinically stable,
      but were considered at high-risk for progression based on anatomical location of
      PN. FDG-PET scans were performed within two weeks of the baseline MRI study.
      Standardized uptake values (SUV) were calculated for all focally active index
      lesions and analyzed for correlation with changes in quantitative MRI over the
      ensuing year. RESULTS: Fifteen of the 18 enrolled patients showed various degrees
      of FDG uptake as focal abnormalities, and these abnormalities corresponded to
      those noted on the MRI scans. Thirteen patients and 19 lesions were evaluable for
      PN volume change. The SUVmax ranged from 0.9 to 4 (median 1.5). There was a
      significant difference in the percent increase in PN volume in the following year
      for lesions that had an SUV > 2 compared to those with lower values (P = 0.016).
      CONCLUSIONS: These findings support the hypothesis that FDG-PET imaging predicts
      PN growth rate, and, therefore, may assist clinician decision making with regard
      to treatment of PN and enrollment in clinical trials.

PMID- 18071637
TI  - A novel method for low load friction testing on living cells.
AB  - A low load tribology technique for studying the effects of friction on living
      cells was developed. Results show a direct relationship between the coefficient
      of friction (COF) and the extent of cell damage. The COF, mu, for a glass pin on
      an intact layer of human corneal epithelial cells is determined to be on the
      order of mu = 0.05 +/- 0.02 (n = 16). The correlations between applied normal
      load and extent of cell damage, as well as between number of reciprocation cycles
      and cell damage, are reported. It is also found that cell damage can occur when a
      loading force as low as 0.5 mN is applied, although the cells appear to be
      intact.

PMID- 18071638
TI  - Purification and characterization of aprotinin from porcine lungs.
AB  - Aprotinin, the most studied serine proteinase inhibitor, was isolated from
      porcine lung for the first time. The purified porcine aprotinin had an Mr value
      of approximately 7 kDa. It cross-reacted with polyclonal serum anti-commercial
      aprotinin. About 1 microg porcine aprotinin inhibited 6 microg trypsin whereas 1
      microg commercial soybean inhibitor inhibited only 1 microg trypsin. The
      aprotinin gene was also isolated from porcine lung: the deduced amino acid
      sequence showed 74% identity to bovine aprotinin.

PMID- 18071640
TI  - Production of L-phenylacetylcarbinol by microbial transformation in polyethylene
      glycol-induced cloud point system.
AB  - Microbial transformation of benzaldehyde into L: -phenylacetylcarbinol by whole
      cell Saccharomyces cerevisiae has been carried out in a novel polyethylene glycol
      (PEG)-induced cloud point system. The system is composed of 80 g PEG 20,000, 75
      ml Triton X-100, 20 g peptone, 10 g yeast extract, 25 g glucose, 1 g
      MgSO(4).7H(2)O, 0.05 g CaCl(2).2H(2)O, 35 g Na(2)HPO(4).12H(2)O, and 10.7 g
      citric acid per liter of tap water. The microbial transformation is conducted at
      0.6 ml of acetaldehyde (35% volume content), 0.9 ml of benzaldehyde, and 7 g of
      wet cell per 100 ml of the PEG-induced cloud point system. Under the conditions,
      a relatively longer-term bioactivity of whole cell microorganism in the PEG
      induced cloud point system has been achieved. A fed-batch microbial
      transformation process with a discrete addition of glucose and substrate gets a
      high final product concentration of about 8 g/l.

PMID- 18071641
TI  - Purification and characterization of a novel beta-agarase, AgaA34, from
      Agarivorans albus YKW-34.
AB  - An extracellular beta-agarase (AgaA34) was purified from a newly isolated marine
      bacterium, Agarivorans albus YKW-34 from the gut of a turban shell. AgaA34 was
      purified to homogeneity by ion exchange and gel filtration chromatographies with
      a recovery of 30% and a fold of ten. AgaA34 was composed of a single polypeptide
      chain with the molecular mass of 50 kDa. N-terminal amino acid sequencing
      revealed a sequence of ASLVTSFEEA, which exhibited a high similarity (90%) with
      those of agarases from glycoside hydrolase family 50. The pH and temperature
      optima of AgaA34 were pH 8.0 and 40 degrees C, respectively. It was stable over
      pH 6.0-11.0 and at temperature up to 50 degrees C. Hydrolysis of agarose by
      AgaA34 produced neoagarobiose (75 mol%) and neoagarotetraose (25 mol%), whose
      structures were identified by matrix-assisted laser desorption ionization time-of
      flight mass spectroscopy and (13)C NMR. AgaA34 cleaved both neoagarohexaose and
      neoagarotetraose into neoagarobiose. The k (cat)/K (m) values for hydrolysis
      agarose and neoagarotetraose were 4.04 x 10(3) and 8.1 x 10(2) s(-1) M(-1),
      respectively. AgaA34 was resistant to denaturing reagents (sodium dodecyl sulfate
      and urea). Metal ions were not required for its activity, while reducing reagents
      (beta-Me and dithiothreitol, DTT) increased its activity by 30%.

PMID- 18071642
TI  - Purification and characterization of an extracellular alpha-L-arabinosidase from
      a novel isolate Bacillus pumilus ARA and its over-expression in Escherichia coli.
AB  - The alpha-L-arabinosidase, AraB, was induced when Bacillus pumilus ARA was grown
      at 50 degrees C in a minimal medium containing xylan. A 56-kDa protein with alpha
      L-arabinosidase activity was purified from culture supernatant to gel
      electrophoretic homogeneity. The optimal activity was at pH 6.4 and 60 degrees C
      over a 10-min assay. The purified enzyme was stable over a pH range of 5.2-7.6
      and had a 1-h half life at 70 degrees C. The enzyme released arabinose from oat
      spelt xylan. Kinetic experiments at 60 degrees C with p-nitrophenyl alpha-L
      arabinofuranoside as substrate gave a K (m), and V (max) of 1.05 mM and 240 U per
      mg of protein. The NH(2)-terminal amino acid sequence of the enzyme was
      determined, and its gene araB was subsequently cloned, sequenced, and over
      expressed in Escherichia coli. The open reading frame of araB consists of a 1,479
      bp fragment encoding a protein of 472 amino acids, which belonged to family 51 of
      the glycoside hydrolases with an identity of 67% to the protein encoded by abfB
      of Bacillus subtilis 168.

PMID- 18071643
TI  - Efficient production of mannosylerythritol lipids with high hydrophilicity by
      Pseudozyma hubeiensis KM-59.
AB  - Mannosylerythritol lipids (MELs) are one of the most promising biosurfactants
      known because of their multifunctionality and biocompatibility. A previously
      isolated yeast strain, Pseudozyma sp. KM-59, mainly produced a hydrophilic MEL,
      namely MEL-C (4-O-[4'-O-acetyl-2',3'-di-O-alka(e)noyl-beta-D: -mannopyranosyl]-D:
      -erythritol). In this study, we taxonomically characterize the strain in detail
      and investigate the culture conditions. The genetic, morphological, and
      physiological characteristics of the strain coincided well with those of
      Pseudozyma hubeiensis. On batch culture for 4 days under optimal conditions, the
      yield of all MELs was 21.8 g/l; MEL-C comprised approximately 65% of the all
      MELs. Consequently, on fed-batch culture for 16 days, the yield reached 76.3 g/l;
      the volumetric productivity was approximately 4.8 g l(-1) day(-1). We further
      examined the surface-active and self-assembling properties of the hydrophilic
      MELs produced by the yeast strain. They showed higher emulsifying activities
      against soybean oil and a mixture of hydrocarbons (2-methylnaphtarene and
      hexadecane, 1:1) than the synthetic surfactants tested. On water penetration
      scans, they efficiently formed lyotropic liquid crystalline phases such as
      myelines and lamella (L alpha) in a broad range of their concentrations,
      indicating higher hydrophilicity than conventional MELs. More interestingly,
      there was little difference in the liquid crystal formation between the crude
      product and purified MEL-C. The present glycolipids with high hydrophilicity are
      thus very likely to have practical potential without further purification and to
      expand the application of MELs especially their use in washing detergents and oil
      in-water-type emulsifiers.

PMID- 18071644
TI  - One-base excess adaptor ligation method for walking uncloned genomic DNA.
AB  - This report describes a novel and efficient method for walking the sequence of a
      genomic deoxyribonucleic acid (DNA) from a known region to an unknown region
      based on an oligodeoxynucleotide (oligo) cassette-mediated polymerase chain
      reaction technique. In this method, genomic DNA is digested by a restriction
      enzyme that generates a sticky 5'-end, followed by ligation of a one-base excess
      oligo-adaptor using T4 DNA ligase. The adaptor consists of two complementary
      oligos that form the same sticky end as the digested genomic DNA fragments,
      except that the 5'-overhang base overlaps the corresponding 3'-end base of the
      restriction site. This overhanging terminal base prevents ligation between the
      adaptors, and the appropriate molar ratio of adaptor to genomic DNA enables
      specific amplification of the target sequence. T4 DNA ligase catalyzes both the
      ligation of the phosphorylated overhang base of the adaptor to genomic DNA and
      the excision of the corresponding 3'-terminal base of the genomic DNA. This
      sequence-specific exonuclease activity of T4 DNA ligase was confirmed by ligation
      of an alternative adaptor in which the 5'-terminal base was not consistent with
      the corresponding 3'-terminal base. Using this technique, the 3'- and 5'-flanking
      sequences of the catalase gene of the ciliate Paramecium bursaria were
      determined.

PMID- 18071645
TI  - Genetic and biochemical characterization of a 4-hydroxybenzoate hydroxylase from
      Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum uses 4-hydroxybenzoic acid (4HBA) as sole carbon
      source for growth. Previous studies showed that 4HBA was taken up into cells via
      PcaK, and the aromatic ring was cleaved via protocatechuate 3,4-dioxygenase. In
      this study, the gene pobA ( Cg ) (ncgl1032) involved in the conversion of 4HBA
      into 3,4-dihydroxybenzoate (protocatechuate) was identified, and the gene product
      PobA (Cg) was characterized as a 4HBA 3-hydroxylase, which is a homodimer of
      PobA(Cg). The pobA (Cg) is physically associated with pcaK and formed a putative
      operon, but the two genes were located distantly to the pca cluster, which encode
      other enzymes for 4HBA/protocatechuate degradation. This new 4HBA 3-hydroxylase
      is unique in that it prefers NADPH to NADH as a cosubstrate, although its
      sequence is similar to other 4HBA 3-hydroxylases that prefer NADH as a
      cosubstrate. Sited-directed mutagenesis on putative NADPH-binding sites, D38 and
      T42, further improved its affinity to NADPH as well as its catalytic efficiency.

PMID- 18071646
TI  - Biochemical characterization of a glycoside hydrolase family 61 endoglucanase
      from Aspergillus kawachii.
AB  - The glycoside hydrolase family 61 endoglucanase from Aspergillus kawachii
      (AkCel61) is a modular enzyme that consists of a catalytic domain and a
      carbohydrate-binding module belonging to family 1 (CBM1) that are connected by a
      Ser-Thr linker region longer than 100 amino acids. We expressed the recombinant
      AkCel61, wild-type enzyme (rAkCel61), and a truncated enzyme consisting of the
      catalytic domain (rAkCel61DeltaCBM) in Pichia pastoris and analyzed their
      biochemical properties. Purified rAkCel61 and rAkCel61DeltaCBM migrated on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and were
      demonstrated to have apparent molecular masses of 81,000 and 34,000 Da,
      respectively. After treatment with endoglycosidase H, both proteins showed an
      increase in mobility, thus, demonstrating estimated molecular masses of 78,000
      and 28,000 Da, respectively. Mass spectrometry analysis revealed that rAkCel61
      and rAkCel61DeltaCBM expressed in P. pastoris are heterogeneous due to protein
      glycosylation. The rAkCel61 protein bound to crystalline cellulose but not to
      arabinoxylan. The rAkCel61 and rAkCel61DeltaCBM proteins produced small amounts
      of oligosaccharides from soluble carboxymethylcellulose. They also exhibited a
      slight hydrolytic activity toward laminarin. However, they showed no detectable
      activity toward microcrystalline cellulose, arabinoxylan, and pectin. Both
      recombinant enzymes also showed no detectable activity toward p-nitrophenyl beta
      D: -glucoside, p-nitrophenyl beta-D: -cellobioside, and p-nitrophenyl beta-D 
      cellotrioside.

PMID- 18071647
TI  - High-cell-density cultivation for co-production of ergosterol and reduced
      glutathione by Saccharomyces cerevisiae.
AB  - Two different high-cell-density cultivation processes based on the mutant
      Saccharomyces cerevisiae GE-2 for simultaneous production of glutathione and
      ergosterol were investigated. Compared with keeping the ethanol volumetric
      concentration at a constant low level, feedback control of glucose feeding rate
      (F) by keeping the descending rate of ethanol volumetric concentration
      (DeltaE/Deltat) between -0.1% and 0.15% per hour was much more efficient to
      achieve a high glutathione and ergosterol productivity. This bioprocess overcomes
      some disadvantages of traditional S. cerevisiae-based cultivation process,
      especially shortening cultivation period and making the cultivation process
      steady-going. A classical on or off controller was used to manipulate F to
      maintain DeltaE/Deltat at its set point. The dry cell weight, glutathione yield
      and ergosterol yield reached 110.0 +/- 2.6 g/l, 2,280 +/- 76 mg/l, and 1,510 +/-
      28 mg/l in 32 h, respectively.

PMID- 18071649
TI  - Risk factors for decreased bone density and effects of HIV on bone in the
      elderly.
AB  - Most studies of bone density in HIV-infected individuals focus on young men. This
      study compares differences in bone density in elderly HIV positive men and women
      to HIV negative controls. Bone density was lower in the lumbar spine and hip in
      the HIV-infected group. Antiretrovirals may be associated with decreased bone
      mineralization. INTRODUCTION: Individuals with human immunodeficiency virus (HIV)
      may be at increased risk for osteoporosis. Prolonged exposures to HIV and/or
      antiretroviral therapy are possible causes for this association. This study
      compares differences in bone mineral density (BMD) in elderly HIV positive men
      and women to HIV negative controls. METHODS: A cross-sectional study was
      conducted among 57 HIV-infected and 47 HIV negative subjects over age 55. BMD at
      the lumbar spine and total hip and markers of bone turnover were compared.
      RESULTS: BMD was borderline lower in the lumbar spine and significantly lower in
      the hip in the HIV-infected group. Controlling for age, sex, race and body mass
      index, differences between the groups were significant at both sites. There was
      no difference in markers of bone turnover between the groups. Tenofovir use was
      significantly associated with decreased BMD at the spine while protease inhibitor
      use was significantly associated with decreased BMD at the hip. CONCLUSION:
      Elderly men and women with HIV have lower bone mass than HIV negative controls.
      Decreased body mass index was the most important risk factor associated with
      decreased BMD. Bone demineralization was observed among HIV-infected subjects
      receiving either tenofovir or a protease inhibitor.

PMID- 18071648
TI  - Back pain in osteoporotic vertebral fractures.
AB  - This review article examines the epidemiology and pathogenesis of back pain and
      vertebral fractures in osteoporosis, reviewing the management of pain in patients
      with vertebral fractures and the direct and indirect effect of osteoporosis
      treatments on back pain. INTRODUCTION: The management of patients with vertebral
      fractures has largely concentrated on the prevention of further fractures by the
      treatment of underlying osteoporosis, with drug treatment for acute and chronic
      back pain and the non-pharmacological management of vertebral fractures receiving
      less attention. DISCUSSION: Emerging evidence suggests that, in addition to
      reducing the incidence of vertebral fractures, calcitonin, intravenous
      bisphosphonates and teriparatide may also have a direct effect on bone pain.
      Targeted analgesia, tailored to individual need is often required in both the
      acute and chronic phases following vertebral fracture. Vertebroplasty and
      kyphoplasty have also been approved for use in the management of vertebral
      fractures and may prove useful in selected patients unresponsive to conventional
      pain relief. There is some evidence to support the use of individualised tailored
      exercise programmes aimed at strengthening back muscles to maintain bone density
      and reduce further fracture incidence. In addition the use of specific orthoses
      may help to reduce kyphosis, improve mobility and reduce pain. CONCLUSION:
      Chronic back pain associated with vertebral fracture provides a great challenge
      to health care professionals and the patient. This demands a combination of
      options, including not only therapeutic interventions, but also physiotherapy,
      psychological support and patient education.

PMID- 18071650
TI  - The cost-effectiveness of the treatment of high risk women with osteoporosis,
      hypertension and hyperlipidaemia in Sweden.
AB  - This paper assessed the cost-effectiveness of the treatment of high risk women
      with osteoporosis, hypertension and hyperlipidaemia in Sweden, using one model
      and a societal perspective. Cost-effective scenarios were found in all these
      chronic disorders. These findings are of relevance for decisions on the efficient
      allocation of health care resources. INTRODUCTION: There is a need to assess the
      cost-effectiveness (CE) of treatment of osteoporosis from a societal perspective
      and to relate this to the CE of interventions in other disease areas. This is of
      relevance for decisions on the efficient allocation of health care resources
      within and between disease areas. The purpose of the paper was to estimate the CE
      of the treatment and prevention of osteoporosis and to put that into the
      perspective of treating hypertension and hyperlipidaemia. The CE was assessed for
      different high risk female populations aged 50-80 years. METHODS: The estimation
      of CE was based on a model populated with data for Sweden. RESULTS: Compared to
      no intervention, a 5-year treatment of osteoporosis, hypertension, and
      hyperlipidaemia, is cost effective for most of the assessed high risk female
      populations. The cost per gained quality adjusted life year (QALY) for the
      treatment of a 70-year-old woman never exceeded SEK 330,000 (US$ 44,000), which
      is generally judged as an acceptable cost for a gained QALY. CONCLUSIONS: The
      study demonstrates that it is possible to produce reliable estimates of the CE of
      treatments in different disease areas within the context of a single model.

PMID- 18071652
TI  - Toll-Like receptors (TLRs) and their ligands.
AB  - The innate immune system is an evolutionally conserved host defense mechanism
      against pathogens. Innate immune responses are initiated by pattern recognition
      receptors (PRRs), which recognize microbial components that are essential for the
      survival of the microorganism. PRRs are germline-encoded, nonclonal, and
      expressed constitutively in the host. Different PRRs react with specific ligands
      and lead to distinct antipathogen responses. Among them, Toll-like receptors
      (TLRs) are capable of sensing organisms ranging from bacteria to fungi, protozoa,
      and viruses, and they play a major role in innate immunity. Here, we review the
      mechanism of pathogen recognition by TLRs.

PMID- 18071651
TI  - Salmon calcitonin: a review of current and future therapeutic indications.
AB  - Salmon calcitonin, available as a therapeutic agent for more than 30 years,
      demonstrates clinical utility in the treatment of such metabolic bone diseases as
      osteoporosis and Paget's disease, and potentially in the treatment of
      osteoarthritis. This review considers the physiology and pharmacology of salmon
      calcitonin, the evidence based research demonstrating efficacy and safety of this
      medication in postmenopausal osteoporosis with potentially an effect on bone
      quality to explain its abilities to reduce the risk of spine fracture, the
      development of an oral salmon calcitonin preparation, and the therapeutic
      rationale for this preparation's chondroprotective effect in osteoarthritis.

PMID- 18071653
TI  - Signalling of toll-like receptors.
AB  - Since Toll-like receptor (TLR) signaling was found crucial for the activation of
      innate and adaptive immunity, it has been the focus of immunological research.
      There are at least 13 identified mammalian TLRs, to date, that share similarities
      in their extracellular and intracellular domains. A vast number of ligands have
      been identified that are specifically recognized by different TLRs. As a response
      the TLRs dimerize and their signaling is initiated. The molecular basis of that
      signaling depends on the conserved part of their intracellular domain; namely the
      Toll/IL-1 receptor (TIR) domain. Upon TLR dimerization a TIR-TIR structure is
      formed that can recruit TIR-containing intracellular proteins that mediate their
      signaling. For this reason these proteins are named adapters. There are five
      adapters identified so far named myeloid differentiation primary response protein
      88 (MyD88), MyD88-adapter like (Mal) or TIR domain-containing adapter (TIRAP),
      TIR domain-containing adapter inducing interferon-beta (IFN-beta) (TRIF) or TIR
      containing adapter molecule-1 (TICAM-1), TRIF-related adapter molecule (TRAM) or
      TICAM-2, and sterile alpha and HEAT-Armadillo motifs (SARM). The first four play
      a fundamental role in TLR-signaling, defining which pathways will be activated,
      depending on which of these adapters will be recruited by each TLR. Among these
      adapter proteins MyD88 and TRIF are now considered as the signaling ones and
      hence the TLR pathways can be categorized as MyD88-dependent and TRIF-dependent.

PMID- 18071654
TI  - TLR9-mediated recognition of DNA.
AB  - The mammalian immune system senses pathogens through pattern recognition
      receptors (PRRs) and responds with activation. The Toll-like receptor (TLR)
      family that consists of 13 receptors plays a critical role in this process.
      TLRmediated signaling activates immune cells and leads to an innate immune
      response with subsequent initiation of an adaptive immune response. Toll-like
      receptor 9 (TLR9) recognizes deoxyribonucleic acid (DNA) leading to cellular
      activation and cytokine production influencing the immune response against
      viruses and bacteria. The stimulation of TLR9 will be exploited for adjuvant
      therapy and treatment of cancer or allergy. In this review we will discuss TLR9
      ligands, TLR9 expression, signaling, and the therapeutic potential of TLR9
      ligands in treatment of infectious or allergic diseases and cancer.

PMID- 18071655
TI  - RNA recognition via TLR7 and TLR8.
AB  - In this chapter we focus on immunorecognition of RNA by two members of the family
      of Toll-like receptors (TLRs), TLR7, and TLR8. While any long single-stranded RNA
      is readily recognized by both TLR7 and TLR8, sequencedependent activation of TLR7
      and TLR8 becomes more evident when using short RNA oligonucleotides. RNA
      oligonucleotides containing sequence motifs for TLR7 and TLR8 are termed is RNA
      (immunostimulatory RNA). Moreover, short doublestranded RNA oligonucleotides as
      used for siRNA (short interfering RNA) containing such sequences function
      primarily as ligands for TLR7 but not TLR8. Even in the presence of appropriate
      sequence motifs, RNA is not detected by TLR7 and TLR8 when certain chemical
      modifications are present. Both immunological recognition and ignorance are
      relevant for the development of RNA-based therapeutics, depending on the clinical
      setting for which they are developed.

PMID- 18071656
TI  - Fungal Recognition by TLR2 and Dectin-1.
AB  - The innate immune system utilizes multiple receptors to recognize fungal
      pathogens, and the net inflammatory response is controlled by interactions
      between these receptors. Many fungi are recognized, at least in part, by Toll
      like receptor 2 (TLR2) and Dectin-1. Examination of the roles these receptors
      play together and on their own is a useful model for understanding the interplay
      between innate immune receptors. This review focuses on the role(s) of TLR2 and
      Dectin-1 in triggering inflammatory responses, transcription factor activation,
      phagocytosis, and reactive oxygen production in response to fungi.

PMID- 18071657
TI  - Heat shock proteins and toll-like receptors.
AB  - Researchers have only just begun to elucidate the relationship between heat shock
      proteins (HSP) and Toll-like receptors (TLR). HSP were originally described as an
      intracellular molecular chaperone of naive, aberrantly folded, or mutated
      proteins and primarily implicated as a cytoprotective protein when cells are
      exposed to stressful stimuli. However, recent studies have ascribed novel
      functions to the Hsp70 protein depending on its localization: Surface-bound Hsp70
      specifically activate natural killer (NK) cells, while Hsp70 released into the
      extracellular milieu specifically bind to Toll-like receptors (TLR) 2 and 4 on
      antigen-presenting cells (APC) and exerts immunoregulatory effects, including
      upregulation of adhesion molecules, co-stimulatory molecule expression, and
      cytokine and chemokine release-a process known as the chaperokine activity of
      Hsp70. This chapter discusses the most recent advances in the understanding of
      heat shock protein (HSP) and TLR interactions in general and highlights recent
      findings that demonstrate Hsp70 is a ligand for TLR and its biological
      significance.

PMID- 18071658
TI  - Nucleic acid recognition receptors in autoimmunity.
AB  - Recent studies in mouse models of systemic autoimmune diseases have drawn
      attention to the involvement of Toll-like receptors (TLRs) in the generation of
      autoreactive immune responses. The endosomally localized TLRs7 and 9 are
      activated by autoimmune complexes containing self DNA and RNA in B lymphocytes
      and dendritic cells. These endogenous TLR ligands act as autoadjuvants providing
      a stimulatory signal together with the autoantigen and thus contribute to break
      peripheral tolerance against self antigens in systemic lupus erythematosus (SLE),
      for example. In vivo studies in SLE mouse models demonstrate an essential role
      for TLR7 in the generation of RNA-containing antinuclear antibodies and
      deposition of pathogenic immune complexes in the kidney. TLR9, however, appears
      to have immunostimulatory as well as regulatory functions in SLE mouse models.
      Type I Interferon, which is produced by plasmacytoid dendritic cells in response
      to autoimmune complexes containing RNA and DNA recognized by TLR7 and 9 acts as a
      potent amplifier of the autoimmune response. TLR-independent recognition of self
      nucleic acids by cytosolic RNA and DNA sensors may also play a role in the
      generation of autoimmune responses. Defects in protective mechanisms, which
      normally prevent immunostimulation by self nucleic acids in healthy individuals,
      promote the development of autoimmune diseases. For example, defects in nucleases
      that clear nucleic acids derived from apoptotic material, changes in the level
      and localization of TLR expression, defects in negative regulators of TLR
      signaling, or changes in the posttranscriptional modification of mammalian DNA
      and RNA may contribute to autoreactive responses. A better understanding of the
      exact function of different nucleic acid recognition receptors in the development
      of systemic autoimmunity will allow targeting of these innate immune receptors
      for the therapy of patients with systemic autoimmune diseases.

PMID- 18071659
TI  - Dendritic cell subsets and toll-like receptors.
AB  - Toll-like receptors exist as highly conserved pathogen sensors throughout the
      animal kingdom and they represent a key family of molecules bridging the ancient
      innate and adaptive immune systems. The first molecules of adaptive immunity
      appeared in the cartilaginous fishes and, with these, major histocompatibility
      proteins and cells expressing these molecules, and thus, by definition, the
      advent of antigen-presenting cells and the "professional" antigen-presenting
      cells, the dendritic cells. Dendritic cells themselves are highly specialized
      subsets of cells with the major roles of antigen presentation and stimulation of
      lymphocytes. The dendritic cell functions of inducing immunity are regulated by
      their own activation status, which is governed by their encounter with pathogen
      associated molecular patterns that signal through pattern recognition receptors,
      including Toll-like receptors, expressed at the surface and within the cytoplasm
      and endosomal membranes of dendritic cells. Thus although dendritic cells play a
      crucial role in the induction of adaptive immunity, the adaptive response is
      itself initiated at the level of ancient receptors of the innate immune system. A
      further degree in the complexity of dendritic cell activation is established by
      the fact that not all dendritic cells are equal. Dendritic cells exist as
      multiple subsets that vary in location, function, and phenotype. Distinct
      dendritic cell subsets display great variation in the type of Toll-like receptors
      expressed and consequently variation in the type of pathogens sensed and the
      subsequent type of immune responses initiated.

PMID- 18071660
TI  - Structure of toll-like receptors.
AB  - The ten human Toll-like receptors are able to respond to an extremely diverse
      range of microbial products ranging from di- and tri-acylated lipids to nucleic
      acids. An understanding of the molecular structure adopted by the receptor
      extracellular, transmembrane, and cytoplasmic domains and the way in which these
      structures interact with ligands and downstream signaling adapters can explain
      how recognition and signal transduction are achieved at a molecular level. In
      this article we discuss how the leucine-rich repeats of the receptor ectodomain
      have evolved to bind a wide variety of biological molecules. We also discuss how
      ligand binding induces dimerization of two receptor chains and initiates a series
      of protein conformational changes that lead to a signaling event in the cytoplasm
      of the immune system cell. Thus, the signaling process of the TLRs can be viewed
      as a unidirectional molecular switch.

PMID- 18071661
TI  - Toll-like receptor-agonists in the treatment of skin cancer: history, current
      developments and future prospects.
AB  - This review will briefly cover some important aspects of skin structure and
      function before touching upon fundamental principles of neoplastic cell growth in
      the skin and some of the important molecular pathways involved. After presenting
      evidence for a role of the immune system in shaping the development of skin
      cancer, concepts for tumor immunotherapy with TLR-agonists are introduced from a
      historical point of view. Subsequently, the use of synthetic DNA, synthetic RNA
      and synthetic small immunostimulatory molecules for immunotherapy of early forms
      of epithelial carcinoma (actinic keratoses) and melanoma (lentigo maligna), as
      well as for advanced metastatic melanoma, is comprehensively presented. Finally,
      current developments and future prospects for immunotherapy of occult or
      unresectable melanoma metastastases, the most important clinical problem today,
      are discussed.

PMID- 18071662
TI  - Vaccination with messenger RNA (mRNA).
AB  - Both DNA and mRNA can be used as vehicles for gene therapy. Because the immune
      system is naturally activated by foreign nucleic acids thanks to the presence of
      Toll-like Receptors (TLR) in endosomes (TLR3, 7, and 8 detect exogenous RNA,
      while TLR9 can detect exogenous DNA), the delivery of foreign nucleic acids
      usually induces an immune response directed against the encoded protein. Many
      preclinical and clinical studies were performed using DNA-based experimental
      vaccines. However, no such products are yet approved for the human population.
      Meanwhile, the naturally transient and cytosolically active mRNA molecules are
      seen as a possibly safer and more potent alternative to DNA for gene vaccination.
      Optimized mRNA (improved for codon usage, stability, antigen-processing
      characteristics of the encoded protein, etc.) were demonstrated to be potent gene
      vaccination vehicles when delivered naked, in liposomes, coated on particles or
      transfected in dendritic cells in vitro. Human clinical trials indicate that the
      delivery of mRNA naked or transfected in dendritic cells induces the expected
      antigen-specific immune response. Follow-up efficacy studies are on the way.
      Meanwhile, mRNA can be produced in large amounts and GMP quality, allowing the
      further development of mRNA-based therapies. This chapter describes the structure
      of mRNA, its possible optimizations for immunization purposes, the different
      methods of delivery used in preclinical studies, and finally the results of
      clinical trial where mRNA is the active pharmaceutical ingredient of new
      innovative vaccines.

PMID- 18071663
TI  - [Video-assisted mediastinoscopic surgery].
AB  - Introduced in the 1990s, videomediastinoscopes dramatically improved imaging of
      the mediastinal structures, and made mediastinoscopy more standardized, user
      friendly, and accessible to trainees. Not surprisingly they have been replacing
      conventional mediastinoscopes for routine biopsy and staging procedures. However
      it was development of the two-bladed spreadable videomediastinoscope by Linder
      and Dahan that allowed increased exposure, bimanual dissection, and thus the
      development of new minimally invasive surgical techniques. The best documented
      method is video-assisted mediastinoscopic lymphadenectomy (VAMLA), which enables
      extremely accurate staging and definitive mediastinal surgery.

PMID- 18071664
TI  - [Immunoadsorption for treatment of dilated cardiomyopathy].
AB  - Abnormalities of the cellular and humoral immune system have been described in
      patients with dilated cardiomyopathy (DCM). For patients with DCM, immunochemical
      analyses of myocardial biopsies have demonstrated myocardial inflammation.
      Various circulating cardiac antibodies have been detected among DCM patients.
      Circulating antibodies are extractable by immunoadsorption. Recent open
      controlled pilot studies showed that removal of antibodies by immunoadsorption
      induces improvement of cardiac function in DCM. Furthermore, it decreases
      myocardial inflammation. This may offer a new therapeutic option for patients
      with severe heart failure due to dilated cardiomyopathy.

PMID- 18071665
TI  - [Dilated cardiomyopathy as a genetic disease: molecular and clinical aspects].
AB  - Dilated cardiomyopathy is a disease of heterogenous etiology. In up to 50% of
      cases, familial aggregation is observed. During the past decade, several DCM
      causing mutations could be identified, several of these in sarcomeric proteins. A
      specific component of the sarcomere, the z-disc, appears to be a "hot spot" in
      the molecular pathogenesis of DCM. Yet, mutations in proteins of the sarcolemma,
      the cytoskeleton, as well as the nuclear membrane can also lead to dilated
      cardiomyopathy. Morever, in addition to the monogenetic causes of cardiomyopathy,
      the genetic background of the individual patient may critically determine disease
      progression and the response to therapy. In the initial clinical evaluation of a
      patient newly diagnosed with DCM, it is important to obtain a careful family
      history in order to detect and treat additional family members which may be
      affected. Moreover, extracardiac manifestations of genetic DCM, such as skeletal
      muscle involvement, should be excluded. We anticipate that the elucidation of
      additional DCM disease genes as well as the underlying molecular pathways should
      lead to the development of novel specific therapies in the future.

PMID- 18071666
TI  - [Translational medicine--from basic research to clinical practice. 38th congress
      of the Society for Nephrology and 40th annual meeting of the German Working Group
      on Clinical Nephrology, 22-25 September 2007 in Munich].

PMID- 18071667
TI  - Microbial communities and immigration in volcanic environments of Canary Islands
      (Spain).
AB  - Volcanic eruptions originated the Canary Islands (Spain), and today, different
      landscapes clearly show that active volcanism. The microbial communities present
      in these volcanic environments, both at high (above 70 degrees C) and moderate
      (25-35 degrees C) temperatures, were analyzed. Rock samples were processed using
      molecular techniques based on both DNA and RNA and complemented with the culture
      of microorganisms at a wide range of temperatures. Microorganisms detected
      through RNA-based molecular surveys were mostly related to mesophilic
      microorganisms, while representatives of hyperthermophiles were not detected. RNA
      decay curves at 80 degrees C resulted in half-life estimates of less than 2 min
      for mesophilic microorganisms, supporting a recent and continuous arrival of
      microorganisms to the high temperature sampled sites. This study constitutes a
      unique experimental approach showing a great natural potential of microorganisms
      to spread out to different natural environments. The implications are of great
      interest for the biogeography, dispersal, and potential distribution of
      microorganisms, and their genetic information, in natural environments.

PMID- 18071668
TI  - Mapping quantitative trait loci associated with barley net blotch resistance.
AB  - Net blotch of barley, caused by Pyrenophora teres Drechs., is an important foliar
      disease worldwide. Deployment of resistant cultivars is the most economic and eco
      friendly control method. This report describes mapping of quantitative trait loci
      (QTL) associated with net blotch resistance in a doubled-haploid (DH) barley
      population using diversity arrays technology (DArT) markers. One hundred and
      fifty DH lines from the cross CDC Dolly (susceptible)/TR251 (resistant) were
      screened as seedlings in controlled environments with net-form net blotch (NFNB)
      isolates WRS858 and WRS1607 and spot-form net blotch (SFNB) isolate WRS857. The
      population was also screened at the adult-plant stage for NFNB resistance in the
      field in 2005 and 2006. A high-density genetic linkage map of 90 DH lines was
      constructed using 457 DArT and 11 SSR markers. A major NFNB seedling resistance
      QTL, designated QRpt6, was mapped to chromosome 6H for isolates WRS858 and
      WRS1607. QRpt6 was associated with adult-plant resistance in the 2005 and 2006
      field trials. Additional QTL for NFNB seedling resistance to the more virulent
      isolate WRS858 were identified on chromosomes 2H, 4H, and 5H. A seedling
      resistance QTL (QRpts4) for the SFNB isolate WRS857 was detected on chromosome 4H
      as was a significant QTL (QRpt7) on chromosome 7H. Three QTL (QRpt6, QRpts4,
      QRpt7) were associated with resistance to both net blotch forms and lines with
      one or more of these demonstrated improved resistance. Simple sequence repeat
      (SSR) markers tightly linked to QRpt6 and QRpts4 were identified and validated in
      an unrelated barley population. The major 6H QTL, QRpt6, may provide adequate
      NFNB field resistance in western Canada and could be routinely selected for using
      molecular markers in a practical breeding program.

PMID- 18071669
TI  - Can persistent organic pollutants explain the association between serum gamma
      glutamyltransferase and type 2 diabetes?
AB  - The results of several epidemiological studies of serum gamma-glutamyltransferase
      (GGT) led us to hypothesise that associations of GGT within its normal range with
      type 2 diabetes may reflect detrimental effects of xenobiotics found in the
      environment, such as persistent organic pollutants (POPs). Epidemiological
      observations showed that serum GGT activity within its normal range strongly
      predicted future type 2 diabetes; the predictability of diabetes from obesity was
      low with GGT at the low end of the normal range; and GGT showed a positive
      association with known markers of oxidative stress or inflammation. Experimental
      findings on cellular GGT suggest that serum GGT levels within the normal range
      may reflect oxidative stress related to the re-synthesis of intracellular
      glutathione; however, this interpretation is not completely satisfying because,
      in its role of regenerating intracellular glutathione, GGT activity should be
      antioxidative. Alternatively, serum GGT activity may reflect amounts of
      glutathione conjugates formed during the metabolism of xenobiotics. Accordingly,
      we postulate a two-part hypothesis: that the association of serum GGT with type 2
      diabetes reflects exposure to POPs, as these substances, which have a very long
      half-life, may influence diabetes risk by residing in adipose tissue as endocrine
      disruptors; and that POPs or similar substances may interact with obesity to
      cause type 2 diabetes. Supporting this hypothesis, cross-sectional investigation
      of background exposure to POPs in the National Health and Nutrition Examination
      Survey showed relationships similar to those observed for GGT, including a
      powerful association with prevalent diabetes and no association between obesity
      and diabetes for very low POP concentrations. Our hypothesis can be tested in
      both prospective studies and toxicological studies.

PMID- 18071670
TI  - The association between the IFIH1 locus and type 1 diabetes.
AB  - AIMS/HYPOTHESIS: We set out to validate a recently reported type 1 diabetes
      association from the IFIH1 gene variation in an independent cohort from a
      population of mixed European descent. METHODS: We genotyped five single
      nucleotide polymorphisms in the IFIH1 locus, i.e. rs2111485, rs1990760,
      rs3747517, rs17783344 and rs984971589, in 589 type 1 diabetes nuclear family
      trios (1,767 individuals). RESULTS: This study independently replicated the
      reported genetic association using a family-based approach.
      CONCLUSIONS/INTERPRETATION: The reported type 1 diabetes association is from a
      linkage disequilibrium region including three candidate genes, i.e. FAP, IFIH1
      and GCA. Further variant discovery and fine mapping could help clarify a novel
      type 1 diabetes mechanism.

PMID- 18071672
TI  - A patient with an unusual aetiology of a severe ketoacidosis.

PMID- 18071671
TI  - Clinical applications of photoplethysmography in paediatric intensive care.
AB  - OBJECTIVE: The photoplethysmographic wave is displayed by most pulse oximeters.
      It may be used as a non-invasive alternative to invasive arterial blood pressure
      trace analysis for continuous haemodynamic monitoring in selected situations.
      PATIENTS AND SETTING: Four cardiac patients treated in a tertiary neonatal
      paediatric intensive care unit. MEASUREMENTS: Simultaneous monitoring of the
      photoplethysmographic wave, ECG, and invasive blood pressure. RESULTS AND
      CONCLUSIONS: Photoplethysmography allows for monitoring pulse rate in patients
      with (possible) heart rate/pulse rate dissociation (pacemaker dependency,
      pulsatile ventricular assist device); monitoring sudden changes in heart beat
      volume, which are unrelated to respiration (pulseless electrical activity, pulsus
      alternans); and monitoring respiratory-dependent fluctuations of the
      plethysmographic wave (heart failure, hypovolaemia, asthma, upper airway
      obstruction, pericardial effusion). Deterioration, slowly evolving over time, may
      be detected by this method.

PMID- 18071673
TI  - Two closely related pathways of nicotine catabolism in Arthrobacter
      nicotinovorans and Nocardioides sp. strain JS614.
AB  - A virtually identical nicotine catabolic pathway including the heterotrimeric
      molybdenum enzyme nicotine and 6-hydroxy-pseudo-oxynicotine dehydrogenase, 6
      hydroxy-L: -nicotine oxidase, 2,6-dihydroxy-pseudo-oxynicotine hydrolase, and 2,6
      dihydroxypyridine hydroxylase have been identified in A. nicotinovorans and
      Nocardioides sp. JS614. Enzymes catalyzing the same reactions and similar protein
      antigens were detected in the extracts of the two microorganisms. Nicotine blue
      and methylamine, two end products of nicotine catabolism were detected in the
      growth medium of both bacterial species. Nicotine catabolic genes are clustered
      on pAO1 in A. nicotinovorans, but located chromosomally in Nocardioides sp.
      JS614.

PMID- 18071674
TI  - Comparative studies of ZD0947, a novel ATP-sensitive K(+) channel opener, on
      guinea pig detrusor and aortic smooth muscles.
AB  - The effects of ZD0947, a novel urinary bladder selective ATP-sensitive potassium
      channel (K(ATP) channel) opener, on carbachol-induced contractions of isolated
      guinea pig urinary bladder strips were investigated to compare its ability to
      relax norepinephrine-induced contraction of the aorta. Electrophysiological
      techniques were also utilized to compare the effects of ZD0947 on membrane
      currents between guinea pig detrusor and aortic myocytes. ZD0947 caused a
      significant reduction of the carbachol-induced contractile activity,
      demonstrating a biphasic relaxation (the first and second components). Although
      glibenclamide antagonized the effects of two components for the ZD0947-induced
      relaxation, gliclazide, a selective sulphonylurea receptor 1 (SUR1) antagonist,
      reduced the effects of the first component but not the second component of the
      ZD0947-induced relaxation. ZD0947 also reduced the norepinephrine-induced
      contraction of the aorta. ZD0947 reduced electrical excitability of detrusor
      smooth muscles, inhibiting spike discharges and also hyperpolarizing the membrane
      as measured with microelectrodes. In conventional whole-cell configuration,
      ZD0947 caused a glibenclamide-sensitive K(+) current (i.e., K(ATP) current) at a
      holding potential of -60 mV in guinea pig detrusor and aortic myocytes. The
      current density of ZD0947-induced K(ATP) currents in guinea pig detrusor myocytes
      was significantly larger than that in aortic smooth muscle cells. These results
      show that ZD0947 caused a significant relaxation through the activation of K(ATP)
      channels in detrusor muscle.

PMID- 18071675
TI  - Pharmacokinetics and pharmacodynamics of erythropoietin receptor in healthy
      volunteers.
AB  - The purpose of this study was to apply the target-mediated drug disposition
      (TMDD) pharmacokinetic (PK) model to describe binding, internalization, and
      turnover of erythropoietin receptor (EPOR). This model allows one to determine
      from free drug (C) PK data not only parameters describing linear disposition of
      EPO such as the elimination rate constant (kel) and volume of distribution (Vc),
      but also the total receptor concentration (Rtot0), drug-receptor complex (RC)
      internalization rate constant (kint), as well as synthesis and degradation rate
      constants (ksyn and kdeg) for the receptor turnover. The previously published
      data on PK of recombinant EPO (rHuEPO) in humans and the results of EPOR binding
      studies were used for analysis. The estimated PK parameters were used to simulate
      time courses of free and bound EPOR after IV administration of clinically
      relevant rHuEPO doses. The estimates of kel=0.106 h(-1) and Vc=0.032 l/kg are
      consistent with reported in the literature values of rHuEPO linear disposition
      parameters. The determined value of Rtot0 was 66.35 pM and the half-life for EPOR
      degradation was 8.8 h. Computer simulations showed a very rapid binding phase in
      the EPOR time profile followed by a decline to a nadir, and a subsequent return
      to the baseline. The nadir values decreased with increasing doses and resulted in
      the maximum values of the bound fractions of the total EPOR in the ranges 33-99%.
      At the baseline conditions, only 3.1% of EPOR were occupied. The saturation of
      EPOR was correlated with the time C remained above the KD level. In conclusion,
      the time courses of serum rHuEPO concentrations contain information about
      internalization and turnover of EPOR. Kinetics of EPOR can be utilized to
      determine the relationship between the pharmacologic effect and exposure to
      rHuEPO.

PMID- 18071676
TI  - Muscarinic receptor subtypes involved in carbachol-induced contraction of mouse
      uterine smooth muscle.
AB  - Functional muscarinic acetylcholine receptors present in the mouse uterus were
      characterized by pharmacological and molecular biological studies using control
      (DDY and wild-type) mice, muscarinic M2 or M3 single receptor knockout (M2KO,
      M3KO), and M2 and M3 receptor double knockout mice (M2/M3KO). Carbachol (10 nM
      100 microM) increased muscle tonus and phasic contractile activity of uterine
      strips of control mice in a concentration-dependent manner. The maximum carbachol
      induced contractions (Emax) differed between cervical and ovarian regions of the
      uterus. The stage of the estrous cycle had no significant effect on carbachol
      concentration-response relationships. Tetrodotoxin did not decrease carbachol
      induced contractions, but the muscarinic receptor antagonists (11-[[2
      [(diethylaminomethyl)-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b[2,3
      b][1,4]benzodiazepin6-one (AF-DX116), N-[2-[2-[(dipropylamino)methyl]-1
      piperidinyl]ethyl]-5,6-dihydro-6-oxo-11H-pyrido[2,3-b][1,4] benzodiazepine-11
      carboxamide (AF-DX384), 4-diphenylacetoxy-N-methyl-piperidine(4-DAMP), para
      fluoro-hexa hydro-sila-diphenidol (p-F-HHSiD), himbacine, methoctramine,
      pirenzepine, and tropicamide) inhibited carbachol-induced contractions in a
      competitive fashion. The pKb values for these muscarinic receptor antagonists
      correlated well with the known pKi values of these antagonists for the M3
      muscarinic receptor. In uterine strips isolated from mice treated with pertussis
      toxin (100 microg/kg, i.p. for 96 h), Emax values for carbachol were
      significantly decreased, but effective concentration that caused 50% of Emax
      values (EC50) remained unchanged. In uterine strips treated with 4-DAMP mustard
      (30 nM) and AF-DX116 (1 microM), followed by subsequent washout of AF-DX116,
      neither carbachol nor N,N,N,-trimethyl-4-(2-oxo-1-pyrolidinyl)-2-butyn-1-ammonium
      iodide (oxotremorine-M) caused any contractile responses. Both M2 and M3
      muscarinic receptor messenger RNAs were detected in the mouse uterus via reverse
      transcription polymerase chain reaction. Carbachol also caused contraction of
      uterine strips isolated from M2KO mice, but the concentration-response curve was
      shifted to the right and downward compared with that for the corresponding wild
      type mice. On the other hand, uterine strips isolated from M3KO and M2/M3 double
      KO mice were virtually insensitive to carbachol. In conclusion, although both M2
      and M3 muscarinic receptors were expressed in the mouse uterus, carbachol-induced
      contractile responses were predominantly mediated by the M3 receptor. Activation
      of M2 receptors alone did not cause uterine contractions; however, M2 receptor
      activation enhanced M3 receptor-mediated contractions in the mouse uterus.

PMID- 18071677
TI  - Emotional perception modulated by an opioid and a cholecystokinin agonist.
AB  - RATIONALE: The cholecystokinin (CCK) and opioid neuromodulatory systems work in
      an antagonistic fashion and can modulate emotional states and noxious input in
      opposite directions. In this behavioral study, we generalize this idea and
      suggest that CCK and opioids can modulate the processing of other external
      signals, e.g., visual stimuli rather than only noxious input. OBJECTIVES: The
      objective of this study was to determine whether CCK and an opioid agonist could
      modulate the emotional experience of visual stimuli. MATERIALS AND METHODS:
      Thirteen healthy male volunteers viewed standardized pictures with either neutral
      or unpleasant content. Simultaneously, one of three treatments was administered
      in a randomized, double-blind crossover design: the CCKb receptor agonist
      pentagastrin (0.1 microg/kg), the mu-opioid receptor agonist remifentanil (0.0625
      microg/kg), or saline. Self-ratings of the emotional experience of pictures and
      drugs were sampled together with psychological tests and recording of heart rate.
      RESULTS: Pentagastrin treatment increased the rating of unpleasantness for both
      neutral and unpleasant pictures, while it decreased the rating of pleasantness
      for the neutral pictures. These effects did not correlate with the degree of
      general unpleasantness induced by the drug. Remifentanil treatment increased the
      pleasantness for the neutral pictures. While pentagastrin treatment induced a
      heart rate increase, unpleasant pictures induced a heart rate decrease, and the
      magnitude of change in heart rate correlated positively for these conditions.
      CONCLUSIONS: This study shows that the CCK and the opioid system modulate how
      external stimuli are emotionally perceived, suggesting a possible involvement in
      affective disorders.

PMID- 18071679
TI  - Evidence for freely chosen pedalling rate during submaximal cycling to be a
      robust innate voluntary motor rhythm.
AB  - Freely chosen pedalling rate during cycling represents a voluntary rhythmic
      movement. It is unclear to what extent this is influenced by internal (e.g.
      loading on the cardiopulmonary system) and external (e.g. mechanical loading)
      conditions. It is also unclear just how robust a voluntary motor rhythm, the
      freely chosen pedalling rate, actually is. The present study investigated (N = 8)
      whether or not the freely chosen pedalling rate during submaximal cycling was
      affected by separate increases in loading on the cardiopulmonary system (changed
      by exposure to acute simulated altitude of 3,000 m above sea level) and
      mechanical loading (changed by exposure to increased power output and thereby
      pedal force). We also investigated (N = 7) whether or not the freely chosen
      pedalling rate and another voluntary motor rhythm, unimanual unloaded index
      finger tapping rate, shared common characteristics of steadiness and
      individuality over a 12-week period. Results showed that the freely chosen
      pedalling rate was unaffected by increased loading on the cardiopulmonary system
      at constant mechanical loading, and vice versa. Further, the pedalling rate was
      steady in the longitudinal perspective (as was the tapping rate), and like
      tapping rate, pedalling rate was highly individual. In total this indicated that
      freely chosen pedalling rate primarily is a robust innate voluntary motor rhythm,
      likely under primary influence of central pattern generators that again are
      minimally affected by internal and external conditions during submaximal cycling.

PMID- 18071678
TI  - 5-HT(1B) receptor inhibition of alcohol-heightened aggression in mice: comparison
      to drinking and running.
AB  - RATIONALE: Serotonin 5-HT(1B) receptors are promising targets for the management
      of several mood and impulse disorders. OBJECTIVE: These experiments examine a 5
      HT(1B) agonist, CP-94,253, and attempt to distinguish between its effects on
      seeking to perform three rewarding behaviors: aggression, drinking, and wheel
      running. MATERIALS AND METHODS: Male CFW mice perform nose-poke responses that
      are maintained by a fixed interval schedules of 10-min (FI10) schedule to gain
      access to one of three rewarding activities. The first experiment studies mice
      reinforced by the opportunity to confront an intruder mouse after drinking water
      or alcohol; the second studies mice reinforced by the presentation of alcoholic
      or non-alcoholic solutions (i.e., 6% ethanol, 0.05% saccharin vs 0.05%
      saccharin); the third studies mice reinforced by access to a running wheel.
      RESULTS: CP-94,253 (1.0-10 mg/kg i.p.) dose-dependently reduces aggression,
      drinking, and wheel running. Of these behaviors, alcohol-heightened aggression is
      the most sensitive to the 5-HT(1B) receptor agonist (ED50 = 4.8 mg/kg).
      Responding for the opportunity to drink or engage in alcohol-heightened
      aggression is suppressed by the highest dose of CP-94,253, whereas CP-94,253 does
      not affect responding that is reinforced by wheel running or species-typical
      aggression. CONCLUSIONS: These results confirm the inhibitory effects of 5-HT(1B)
      receptor stimulation on aggressive performance and drinking. They also reveal an
      inhibition of voluntary wheel running, contrary to the stimulation of running in
      a novel, open arena. 5-HT(1B) receptor agonists may be particularly useful for
      the treatment of aggressive behavioral disorders, but their efficacy and potency
      appear to be sensitive to the intensity and context of the behavior.

PMID- 18071680
TI  - Guidance of visual direction by topographical vibrotactile cues on the torso.
AB  - Vibration on localised areas of skin can be used to signal spatial orientation,
      multi-directional motion and also to guide arm and hand movements. This study
      investigated the possibility that vibration at loci on the skin might also be
      used to cue gaze direction. Eight subjects made eye or (head + eye) gaze saccades
      in the dark cued by vibration stimulation at discrete loci spaced on a horizontal
      contour across the chest. Saccade and gaze amplitudes, latencies, and directions
      were analysed. In the first experiment, performed without training, subjects
      could only use vibration cues to direct their gaze in cardinal directions and
      gross quadrature. There was a high variability in the relationship between locus
      on the trunk and gaze direction in space, both within and between subjects.
      Saccade latencies ranged from 377 to 433 ms and were related to the loci of
      vibration; the further from the body midline the quicker the response. Since the
      association of skin loci with gaze direction did not appear intuitive a sub-group
      of four subjects were retested after intensive training with feedback until they
      attained criterion on midline identical with 0 degrees and 15 cm (to right/left
      of midline) identical with 45 degrees gaze shifts right and left. Training gave a
      moderate improvement in directional specificity of gaze to a particular locus on
      the skin. Gaze direction was linearly rescaled with respect to skin loci but
      variability and saccade latencies remained high. The uncertainty in the
      relationship between vibration locus and gaze direction and the prolonged
      latencies of responses indicate circuitous neuronal processing. There appears to
      be no pre-existing stimulus-response compatibility mapping between loci on the
      skin and gaze direction. Vibrotactile cues on the skin of the trunk only serve a
      gross indication of visual direction in space.

PMID- 18071682
TI  - The elderly--a challenge for appropriate drug treatment.

PMID- 18071681
TI  - Assessment of urinary mephenytoin metrics to phenotype for CYP2C19 and CYP2B6
      activity.
AB  - OBJECTIVES: (S)-Mephenytoin is selectively metabolised to (S)-4'
      hydroxymephenytoin by CYP2C19. The urinary excretion of 4'-hydroxymephenytoin
      reflects the activity of individual enzymes. We evaluated fractioned urinary
      collection and beta-glucuronidase pre-treatment in order to determine the optimal
      CYP2C19 metrics. We also assessed whether urinary excretion of N
      desmethylmephenytoin (nirvanol) might be a useful CYP2B6 metric in in vivo
      studies. METHODS: A 50-mg dose of mephenytoin was administered to 52 volunteers
      as a component of phenotyping cocktails in four separate studies. Urine was
      collected up to 166 h post-dose. Urinary excretion of 4'-hydroxymephenytoin and
      nirvanol was quantified by liquid chromatography-tandem mass spectrometry, and
      common CYP2C19 and CYP2B6 genotypes were determined. RESULTS: Cumulative
      excretion of 4'-hydroxymephenytoin in urine with beta-glucuronidase treatment
      collected from before mephenytoin administration up to 12-16 h thereafter showed
      the greatest difference between CYP2C19 genotypes and the lowest intra-individual
      variability (7%). Renal elimination of nirvanol was highest for a *4/*4
      individual and lowest for individuals carrying the *5/*5 and *1/*7 genotype, but
      lasted for several weeks, thus making its use in cross-over studies difficult.
      CONCLUSION: Cumulative urinary excretion of 4'-hydroxymephenytoin 0-12 h post
      administration is a sensitive and reproducible metric of CYP2C19 activity,
      enabling the effect of a drug on CYP2C19 to be assessed in a small sample size of
      n=6 volunteers. While nirvanol excretion may reflect CYP2B6 activity in vivo, it
      is not useful for CYP2B6 phenotyping.

PMID- 18071683
TI  - Brainstem venous congestion after transvenous embolization in cavernous dural
      arteriovenous fistula: treatment with stent grafts.

PMID- 18071684
TI  - Imaging of hypospadias: pre- and postoperative appearances.
AB  - Hypospadias is a common condition that is typically diagnosed and repaired in
      early life. Boys with hypospadias can present with complications from their
      surgery months to years later. Imaging in patients with hypospadias is usually
      accomplished by retrograde urethrography (RUG) and less commonly by voiding
      cystourethrography (VCUG). This pictorial essay demonstrates the fluoroscopic
      appearances of hypospadias preoperatively as well as the normal postoperative
      appearance and a variety of complications that can occur.

PMID- 18071685
TI  - Imaging recommendations in paediatric uroradiology: minutes of the ESPR workgroup
      session on urinary tract infection, fetal hydronephrosis, urinary tract
      ultrasonography and voiding cystourethrography, Barcelona, Spain, June 2007.
AB  - We present here a few basic proposals for algorithms and procedures for imaging
      the paediatric genitourinary tract based on initial discussion at a paediatric
      uroradiology symposium and proposals of the ESUR Paediatric Uroradiologic
      Guidelines Subcommittee. These recommendations were developed in the light of new
      knowledge that might influence existing guidelines. Regional, individual and
      local flexibility and variability should be preserved in order to make these
      recommendations applicable throughout Europe. They should help standardize
      dedicated imaging not only in terms of a quality measure to ensure state-of-the
      art patient care, but also in forming a common basis for multi-institutional
      research. There is an urgent need for these guidelines in order to advance our
      understanding of the subject and to gain evidence and improve imaging efficacy.
      Our session worked towards establishing an agreement on imaging indications in
      common paediatric urological conditions, respecting the ALARA principle, and
      patient safety and care, and taking into account state of the art knowledge and
      efficacy aspects. We started the task with a reassessment of (1) imaging in
      urinary tract infection in infants and children, (2) postnatal imaging in mild-to
      moderate neonatal hydronephrosis, (3) how to perform voiding cystourethrography,
      and (4) procedural recommendations for paediatric urosonography. This list is
      incomplete, and future recommendations will be developed, discussed and presented
      at forthcoming meetings.

PMID- 18071686
TI  - MR imaging appearance of laryngeal atresia (congenital high airway obstruction
      syndrome): unique course in a fetus.
AB  - Congenital high airway obstruction syndrome (CHAOS) is a rare life-threatening
      syndrome. Most cases are diagnosed prenatally by US. We report a fetus with this
      syndrome that showed a unique course revealed on MRI. Ultrasonography at 22 weeks
      demonstrated that the fetus had ascites and bilaterally enlarged hyperechoic
      lungs. Congenital infection, congenital cystic adenomatoid malformation or CHAOS
      was suspected. Subsequent MRI performed at 24 weeks demonstrated bilaterally
      enlarged high-signal lungs, dilated bronchi, massive ascites, subcutaneous oedema
      and polyhydramnios. MRI confirmed the diagnosis of CHAOS. A second MRI at 35
      weeks showed that the bilateral lung enlargement, ascites, oedema and
      polyhydramnios had resolved, but that the appearance of the airway was unchanged.
      The infant was delivered by caesarean section at 38 weeks of gestation and
      immediate tracheostomy was performed. This spontaneous regression was explained
      by a tracheo-oesophageal fistula that may have decreased the intrathoracic
      pressure.

PMID- 18071687
TI  - Evaluation of UPJ obstruction before and after pyeloplasty using MR urography.
AB  - This article builds on the previous article in this symposium and shows how MR
      urography contributes to the postoperative evaluation of children with UPJ
      obstruction. By analyzing the postoperative results, we derived new insights into
      their preoperative evaluation. With MR urography we combine simultaneous
      physiological and anatomic evaluation that enables us to identify changes in
      renal pathophysiology that occur in association with impaired drainage and
      obstruction. We studied 35 children before and after pyeloplasty. The pyeloplasty
      was considered successful in 30 and unsuccessful in 5. Both anatomic and
      functional criteria were used. The anatomic parameters included the degree of
      hydronephrosis, the appearance of the renal parenchyma, the quality of the
      nephrogram and the presence of crossing vessels. The functional criteria included
      the renal transit time, the calyceal transit time, the volumetric differential
      function, the Patlak differential function, the difference between the volumetric
      and Patlak differential function and the Patlak number per milliliter of renal
      tissue. No single parameter was sufficient to fully characterize UPJ obstruction,
      but by synthesizing all the information we were able to subdivide UPJ obstruction
      into compensated, decompensated and uropathic kidneys. Decompensated systems had
      the most significant improvement following successful pyeloplasty. Compensated
      systems showed little improvement in renal function, and uropathic kidneys were
      associated with a poor prognosis. It is clear that not all UPJ obstructions are
      the same, and it seems logical that treatment should be individually tailored
      rather than using a standard approach for all cases. Because MR urography can
      identify pathophysiological differences in children with UPJ obstruction that are
      occult to renal scintigraphy, it has an important potential role in identifying
      those who will benefit most from pyeloplasty and those who are probably best
      observed.

PMID- 18071688
TI  - Evaluation of reflux nephropathy, pyelonephritis and renal dysplasia.
AB  - MR urography has the potential to significantly improve our understanding of the
      relationship between reflux nephropathy, pyelonephritis, vesicoureteric reflux
      and renal dysplasia. MR urography utilizes multiple parameters to assess both
      renal anatomy and function and provides a more complete characterization of
      acquired and congenital disease. Pyelonephritis and renal scarring can be
      distinguished by assessing the parenchymal contours and signal intensity.
      Characteristic imaging features of renal dysplasia include small size,
      subcortical cysts, disorganized architecture, decreased and patchy contrast
      enhancement as well as a dysmorphic pelvicalyceal system. Because of its ability
      to subdivide and categorize this heterogeneous group of disorders, it seems
      inevitable that MR urography will replace DMSA renal scintigraphy as the gold
      standard for assessment of pyelonephritis and renal scarring. MR urography will
      contribute to our understanding of renal dysplasia and its relationship to reflux
      nephropathy.

PMID- 18071689
TI  - MR urography evaluation of obstructive uropathy.
AB  - Hydronephrosis and the evaluation of obstructive uropathy are the most common
      indications for MR urography in our practice. Typically our patients fall into
      one of two groups: infants with antenatal hydronephrosis and older children who
      present with abdominal pain, hematuria or urinary tract infection. Obstruction in
      children is usually chronic and partial. Intermittent episodes of increased
      pressure occur when the urine production exceeds the capacity for drainage. MR
      urography uses a fluid and diuretic challenge to assess the hydronephrotic
      kidney. High-quality anatomic images provide a morphologic assessment of the
      hydronephrotic system. Although it is relatively straightforward to determine if
      a system is not obstructed on the basis of the renal transit time (RTT), no
      single parameter is adequate to fully characterize obstruction. By evaluating the
      changes in signal intensity in the renal parenchyma following contrast
      administration, the hydronephrotic systems are classified as compensated or
      decompensated. Delayed RTT and the presence of urine-contrast levels indicate
      stasis. Calyceal transit time and the difference between the volumetric and the
      Patlak differential renal function (vDRF-pDRF) are measures of the physiologic
      changes within the kidney. Additionally, MR urography provides prognostic
      information by assessing the quality of the renal parenchyma and identifying
      uropathy preoperatively. MR urography combines both anatomic and functional
      information in a single test and is capable of providing a comprehensive
      evaluation of obstructive uropathy that could ultimately help select those
      patients most likely to benefit from surgical intervention.

PMID- 18071690
TI  - MR features of isolated uterine relapse in an adolescent with acute lymphoblastic
      leukaemia.
AB  - Relapses of lymphoblastic leukaemia traditionally involve the central nervous
      system and testes in boys. Involvement of the female pelvic organs is frequently
      found at autopsy; however, involvement of the cervical uterus is rare and even
      less commonly symptomatic. A 13-cm uterine mass was discovered in a 15-year-old
      adolescent with a history of lymphoblastic leukaemia during childhood. Pelvic MRI
      was the best tool to assess the size, characteristics and invasive nature of this
      lesion of the uterine cervix. To our knowledge, this is a unique case in that we
      describe the MRI appearance of a relapsing lymphoblastic leukaemic mass both
      before and after treatment.

PMID- 18071691
TI  - MR urography in children: how we do it.
AB  - In this article we introduce the topic of MR urography in children, focusing on
      the details required to obtain consistently high-quality scans. Much of the
      information presented is based on our experience during the last 7 years. We have
      performed almost 1,000 MR urograms in children, and the technique has evolved
      considerably during this time. We have learned through trial and error and have
      improved our protocols to the point that our approach is now standardized and
      reliably generates high-quality studies. From this standardized protocol, further
      refinements in technique can be readily implemented. It is important to remember
      that this clinical application is in its infancy and will improve significantly
      with further technical development. This paper provides an overview of the
      practical issues associated with obtaining high-quality scans as well as an
      introduction into the interpretation of MR urograms.

PMID- 18071692
TI  - MRU post-processing.
AB  - Dynamic magnetic resonance urography (MRU) scans acquired in conjunction with an
      injection of a contrast agent can be used to estimate a number of parameters that
      reflect renal function. This article discusses the methodologies and assumptions
      used in the estimation of these parameters, with special attention to the problem
      of deriving the concentration of the contrast agent from the change in the MR
      signal. The estimates of split renal function derived from MRU are in good
      agreement with those obtained using nuclear medicine studies. The time-intensity
      curves show subtle differences from those measured using nuclear medicine but
      still allow the transit of the contrast agent through the kidney to be assessed.
      Quantitative estimates of renal function (GFR) can be derived from MRU but have
      yet to be validated in a pediatric population.

PMID- 18071693
TI  - Magnetic resonance urography (MRU) course introduction.

PMID- 18071694
TI  - Nephrogenic systemic fibrosis.
AB  - Nephrogenic systemic fibrosis (NSF) is a dermatological fibrosing disease with
      potential systemic manifestations resulting in mild to severe symptoms including
      joint contractures. NSF can be lethal in a subset of cases. It has been recently
      observed that almost all patients with NSF have had severe renal insufficiency
      and have received prior administrations of gadolinium-based contrast agents
      (GBCA). This review will focus on the specific evidence from a retrospective
      study performed at our center in combination with the general experience
      available. Conclusions summarize our current understanding of NSF.
      Recommendations are provided for use of GBCA in clinical MRI practice.
      Conclusions and recommendations include that the risk of inducing NSF is related
      to higher-dose administrations of GBCA and that there are differences in risk
      related to differences in gadolinium-chelate formulation, with the highest
      relative risk associated with gadodiamide (Omniscan, Nycomed Amersham, GE
      Healthcare, Piscataway, N.J.).

PMID- 18071695
TI  - Pyelonephritis, renal scarring, and reflux nephropathy: a pediatric urologist's
      perspective.
AB  - Imaging of children with a clinical diagnosis of pyelonephritis is performed to
      characterize the extent of the infection, to identify associated renal injury and
      to uncover risk factors for future infections and renal damage. Although there is
      general agreement regarding the need for parenchymal imaging and the need to
      exclude processes that are either functionally or anatomically obstructive, there
      is controversy regarding the need for routine cystography, especially when
      parenchymal involvement has not been documented. A protocol that limits the use
      of cystography for evaluation of urinary tract infections must assume that the
      diagnosis of reflux is at least of variable clinical significance. It is now
      clear that vesicoureteral reflux and reflux nephropathy represent a diverse
      population that includes both congenital and acquired processes. MR imaging will
      improve our understanding of vesicoureteral reflux, pyelonephritis and renal
      scarring and might help us to identify and manage those patients most at risk for
      recurrent infections and renal injury. To recognize the potential contributions
      of this newer imaging technique it is helpful to look at our understanding of the
      pathophysiology of pyelonephritis, reflux and reflux nephropathy.

PMID- 18071696
TI  - Renal dysplasia and MRI: a clinician's perspective.
AB  - Renal dysplasia is a common abnormality in children. The role of MRI in
      evaluating children with renal dysplasia is evolving. More information is clearly
      necessary before MRI replaces conventional imaging modalities. In order to
      appropriately use MRI, the radiologist must have an understanding of the clinical
      questions that are important in the management of children with renal dysplasia.
      This review provides background information on renal dysplasia for the pediatric
      radiologist. The focus is on unilateral disease, especially multicystic
      dysplastic kidneys, and bilateral dysplasia, which is the most common cause of
      kidney failure in children. The emphasis is on the important clinical issues, and
      the potential of MRI as a methodology for providing clinically useful information
      not otherwise available from other imaging modalities.

PMID- 18071697
TI  - Chronic partial ureteral obstruction and the developing kidney.
AB  - Although congenital urinary tract obstruction is a common disorder, its
      pathophysiology remains poorly understood and clinical practice is controversial.
      Animal models have been used to elucidate the mechanisms responsible for
      obstructive nephropathy, and the models reveal that renal growth and function are
      impaired in proportion to the severity and duration of obstruction. Ureteral
      obstruction in the neonatal rat or mouse leads to activation of the renin
      angiotensin system, renal infiltration by macrophages, and tubular apoptosis.
      Nephrons are lost by glomerular sclerosis and the formation of atubular
      glomeruli, and progressive injury leads to tubular atrophy and interstitial
      fibrosis. Recovery following release of obstruction depends on the timing,
      severity, and duration of obstruction. Growth factors and cytokines are produced
      by the hydronephrotic kidney, including MCP-1 and TGF-beta1, which are excreted
      in urine and can serve as biomarkers of renal injury. Because MRI can be used to
      monitor renal morphology, blood flow, and filtration rate, its use might supplant
      current imaging modalities (ultrasonography and diuretic renography), which have
      significant drawbacks. Combined use of MRI and new urinary biomarkers should
      improve our understanding of human congenital obstructive nephropathy and should
      lead to new approaches to evaluation and management of this challenging group of
      patients.

PMID- 18071698
TI  - Estimate of myocardial salvage in late presentation acute myocardial infarction
      by comparing functional and perfusion abnormalities in predischarge gated SPECT.
AB  - PURPOSE: We hypothesized that, because of persistent stunning, the extent of post
      treatment functional abnormalities detected using gated single-photon emission
      computed tomography (SPECT) could be representative of the initial risk area in
      acute myocardial infarction (AMI) treated by reperfusion therapy. MATERIALS AND
      METHODS: In 48 AMI patients, we acquired two 99mTc-sestamibi gated SPECT studies
      (at admission with tracer injection before treatment and at discharge 5 to 10
      days later). We assessed the myocardial salvage defined by the admission minus
      predischarge summed rest score, and we compared it with the value obtained by
      subtracting the extent of perfusion defect from the extent of wall motion or wall
      thickening abnormalities in predischarge gated SPECT. Myocardial salvage was
      expressed as salvage index (salvaged myocardium divided by initial risk area).
      RESULTS: There was a good correlation between summed rest score salvage index and
      wall motion (Spearman's rho = 0.754, p < 0.0001) or wall thickening salvage index
      (Spearman's rho = 0.798, p < 0.0001). The wall thickening salvage index was able
      to classify correctly the patients that had a summed rest score salvage index >
      or = 0.10 with 73% sensitivity, 88% specificity, and 83% accuracy. The wall
      motion salvage index was highly sensitive (91%) but poorly specific (13%, p <
      0.002 vs wall thickening salvage index) and less accurate (69%, p < 0.05 vs wall
      thickening salvage index). CONCLUSIONS: 99mTc-sestamibi gated SPECT allows
      assessing myocardial salvage using only post-treatment data. The salvage index
      derived using wall thickening as surrogate of admission perfusion defect
      correlates well with the salvage index measured by comparing pre- and post
      treatment perfusion defects.

PMID- 18071699
TI  - FDG PET/CT findings in primary hyperparathyroidism mimicking multiple bone
      metastases.

PMID- 18071700
TI  - 131I-MIBG therapy in metastatic phaeochromocytoma and paraganglioma.
AB  - PURPOSE: (131)Iodine metaiodobenzylguanidine ((131)I-MIBG) is a
      radiopharmaceutical used for scintigraphic localisation of phaeochromocytomas and
      paragangliomas. The experience with its therapeutic use is limited. We report our
      experience for the treatment of malignant phaeochromocytoma and paraganglioma.
      MATERIALS AND METHODS: The charts of 19 patients with malignant phaeochromocytoma
      (n = 12) or paraganglioma (n = 7), who were treated with (131)I-MIBG, were
      retrospectively reviewed. Four patients (21%) received radiotherapy, three (16%)
      chemotherapy, and in one patient (5%), both chemotherapy and radiotherapy was
      given before (131)I-MIBG therapy. Response to (131)I-MIBG treatment was evaluated
      by objective as tumour response, biochemical and subjective response. RESULTS: Of
      the 19 patients, 13 (68%) were men, 6 (32%) were women. Ages ranged from 22 to 68
      years (median, 47). The median initial dose was 7.4 GBq (200 mCi; range, 6.7 GBq
      25.9 GBq, 180-700 mCi); median cumulative dose was 22.2 GBq (600 mCi; range, 6.8
      GBq-81.4 GBq, 183-2200 mCi). Objective tumour response was achieved in 47% of the
      patients. Biochemical response rate was 67%, and symptomatic response was seen in
      89% of the patients. Overall median follow-up was 29 months, with a range of 3-93
      months. Haematologic complications were the most common side effects and were
      observed in 26% of the patients. CONCLUSION: Our data support that symptomatic
      and biochemical response can be reached with (131)I-MIBG therapy in patients with
      metastatic phaeochromocytoma and paraganglioma. Although complete tumour response
      was not observed, the palliation and control of tumour function by (131)I-MIBG
      therapy may be valuable for the patients.

PMID- 18071701
TI  - Radiation dosimetry of N-([11C]methyl)benperidol as determined by whole-body PET
      imaging of primates.
AB  - PURPOSE: N-([(11)C]methyl)benperidol ([(11)C]NMB) can be used for positron
      emission tomography (PET) measurements of D(2)-like dopamine receptor binding in
      vivo. We report the absorbed radiation dosimetry of i.v.-administered (11)C-NMB,
      a critical step before applying this radioligand to imaging studies in humans.
      MATERIALS AND METHODS: Whole-body PET imaging with a CTI/Siemens ECAT 953B
      scanner was done in a male and a female baboon. After i.v. injection of 444-1221
      MBq of (11)C-NMB, sequential images taken from the head to the pelvis were
      collected for 3 h. Volumes of interest (VOIs) were identified that entirely
      encompassed small organs (whole brain, striatum, eyes, and myocardium). Large
      organs (liver, lungs, kidneys, lower large intestine, and urinary bladder) were
      sampled by drawing representative regions within the organ volume. Time-activity
      curves for each VOI were extracted from the PET, and organ residence times were
      calculated by analytical integration of a multi-exponential fit of the time
      activity curves. Human radiation doses were estimated using OLINDA/EXM 1.0 and
      the standard human model. RESULTS: Highest retention was observed in the blood
      and liver, each with total residence times of 1.5 min. The highest absorbed
      radiation doses were to the heart (10.5 MUGy/MBq) [DOSAGE ERROR CORRECTED] and
      kidney (9.19 MUGy/MBq), [DOSAGE ERROR CORRECTED] making these the critical organs
      for [(11)C]NMB. A heart absorption of 50 mGy would result from an injected dose
      of 4,762 MBq [(11)C]NMB. CONCLUSIONS: Thus, this study suggests that up to 4,762
      MBq of [(11)C]NMB can be safely administered to human subjects for PET studies.
      Total body dose and effective dose for [(11)C]NMB are 2.82 MUGy/MBq [DOSAGE ERROR
      CORRECTED] and 3.7 mSv/kBq, respectively.

PMID- 18071702
TI  - Radiation dosimetry and biodistribution of 11C-ABP688 measured in healthy
      volunteers.
AB  - INTRODUCTION: In this study, we assessed the whole-body biodistribution and
      radiation dosimetry of the new glutamatergic ligand (11)C-ABP688. This ligand
      binds specifically to the metabotropic glutamatergic receptor of subtype 5
      (mGluR5). MATERIALS AND METHODS: The study included five healthy male volunteers
      aged 20-29 years. After intravenous injection of 240-260 MBq, a series of four to
      ten whole-body positron emission tomography/computed tomography scans were
      initiated, yielding 60-80 min of data. Residence times were then calculated in
      the relevant organs, and the software packages Mirdose and Olinda were used to
      calculate the absorbed radiation dose and the effective dose equivalent. RESULTS:
      Of the excreted (11)C activity at 1 hour, approximately 80% were eliminated via
      the hepato-biliary pathway and 20% through the urinary tract. The absorbed dose
      (mGy/MBq) was highest in the liver (1.64 E (-2) +/- 5.08 E (-3)), gallbladder
      (8.13 E (-3) +/- 5.6 E (-3)), and kidneys (7.27 E (-3) +/- 2.79 E (-3)). The
      effective dose equivalent was 3.68 +/- 0.84 microSv/MBq. Brain uptake in the
      areas with high mGluR5 density was 2-3 (SUV). The agreement between the values
      obtained from Mirdose and the Olinda was excellent. CONCLUSION: (11)C-ABP688 is a
      very promising ligand for the investigation of mGluR5 receptors in humans. Brain
      uptake is high and the effective dose equivalent so low that serial examinations
      in the same subject seem feasible.

PMID- 18071703
TI  - Identification of beta thalassemia mutations in South Brazilians.
AB  - We have evaluated the mutation profile in a sample of 127 unrelated beta
      thalassemia (beta thal) individuals, diagnosed through A2 and fetal hemoglobin
      quantification by high-performance liquid chromatography (HPLC) from the
      Brazilian southernmost state, where a flow of Italian immigrants had occurred in
      the late 19th century, mainly from Northern Italy. The molecular analysis was
      performed by DNA sequencing of the most common mutations found in the
      Mediterranean region. The beta 0 codon 39 nonsense mutation was the most frequent
      alteration (50.9%), followed by beta+ IVSI 110 G>A (18.1%), beta 0 IVSI 1 G>A
      (12.9%), beta+ IVSI 6 T>C (9.5%), and other rare mutations (8.6%). The chosen
      gene sequence was able to identify 91% beta-thal mutations in the population
      studied, showing some similarity with allele frequencies of the mainly colonizing
      countries of Rio Grande do Sul state. The comparison of our results to other
      Brazilian studies has shown significant differences. Therefore, we can conclude
      that the genotypic profile of beta-thal shows great variability. Hence, it would
      be arbitrary to infer regional study results as being representative of the
      Brazilian whole population. Brazilian researchers of different regions should
      identify their most frequent genotypes to provide better understanding on this
      disease and state adequate public health policies.

PMID- 18071704
TI  - Impact of celecoxib on capecitabine tolerability and activity in pretreated
      metastatic breast cancer: results of a phase II study with biomarker evaluation.
AB  - BACKGROUND: Preclinical evidence suggests that the cyclo-oxygenase-2 (COX-2)
      enzyme plays an important role in breast cancer progression. The aim of the
      present phase II study was to determine the activity and safety of the
      combination of the COX-2 inhibitor celecoxib with capecitabine in metastatic
      breast cancer (MBC) patients pretreated with anthracyclines and/or taxanes.
      METHODS: Eligible patients received capecitabine 1,000 mg/m(2) twice daily on
      days 1-14 every 21 days and celecoxib 200 mg twice daily, continuously, until
      disease progression or unacceptable toxicity. RESULTS: About 42 pretreated MBC
      patients were enrolled into the study. Median number of previous chemotherapy
      lines for metastatic disease was 2 (0-3). Seven patients (19%) responded to
      treatment while disease stabilization occurred in 17 patients (40.5%). Overall,
      20 patients (47.5%) achieved clinical benefit [objective responses (CR) plus
      stable disease (SD) >/=6 months]. Median time to progression (TTP) and median
      overall survival (OS) were 5.2 and 17.8 months, respectively. Treatment was very
      well tolerated: grade 3 toxicities were observed in only five patients,
      respectively, and no grade 4 adverse events were reported. Celecoxib was never
      discontinued for toxicity. Analysis of COX-2 expression in the 22 patients with
      available tissue revealed a significantly longer TTP and OS for patients whose
      tumors over-expressed COX-2. CONCLUSIONS: The combination of capecitabine and
      celecoxib is active and safe in far advanced MBC patients. Interestingly, this
      association resulted in a lower-than-expected toxicity, as compared to single
      agent capecitabine. The clinical relevance of COX-2 as determinant of sensitivity
      to treatment with celecoxib should be further evaluated in larger series of
      patients.

PMID- 18071705
TI  - Role of TLRs/MyD88 in host resistance and pathogenesis during protozoan
      infection: lessons from malaria.
AB  - Toll-like receptors (TLRs) are important to initiate the innate immune response
      to a wide variety of pathogens. The protective role of TLRs during infection with
      protozoan parasites has been established. In this regard, malaria represents an
      exception where activation of TLRs seems to be deleterious to the host. In this
      article, we review the recent findings indicating the contrasting role of Myeloid
      Differentiation Primary-Response gene 88 (MyD88) and TLRs during malaria and
      infection with other protozoa. These findings suggest that MyD88 may represent an
      Achilles' heel during Plasmodium infection.

PMID- 18071707
TI  - The role of cytokines in inflammatory response after total knee arthroplasty in
      patients with rheumatoid arthritis.
AB  - Surgery and trauma is accompanied by changes in blood levels of certain cytokines
      and chemokines including interleukin-6 (IL-6) and interleukin-8 (IL-8). However,
      there is little data on correlations between local and systemic levels of these
      mediators during orthopedic surgeries in rheumatoid arthritis (RA) patients who
      already show increased levels of proinflammatory cytokines due to their disease.
      We aimed to measure dynamics of blood and drainage fluid levels of IL-6 and IL-8
      in postoperative period in rheumatoid arthritis patients undergoing knee
      replacement surgery and correlate these changes with blood levels of C-reactive
      protein (CRP), body temperature and pain. We report that blood and drainage fluid
      levels of IL-6 and IL-8 showed significantly increasing trend during the 36-h
      period after the surgery. Drainage fluid levels of both cytokines were
      significantly higher in comparison with blood, indicating their local production
      in the operated joint. In contrast, levels of CRP were higher in blood than in
      drainage fluid. Despite the fact that the levels of tested cytokines had already
      been high in RA patients before surgery, we conclude that after surgery their
      levels were being much significantly enough high in drainage fluid to reflect
      dominated local inflammatory reaction to surgical stress and trauma.

PMID- 18071706
TI  - Severe sepsis and Toll-like receptors.
AB  - Severe sepsis dominates the mortality of non-cardiac intensive care units. The
      ingenious Toll-like receptor (TLR) system can recognise many infectious organisms
      through relatively few receptors to trigger pro-inflammatory and anti
      inflammatory cytokine release. Further complexity arises from positive and
      negative signalling feedback loops. Severe sepsis may be a consequence of an
      inappropriately excessive response or inadequate endogenous negative feedback.
      Therapies targeting these pathways are currently being evaluated. Alternatively,
      in clinical scenarios such as compensatory anti-inflammatory response syndrome,
      chronic viral sepsis or inadequate vaccine function, TLR signalling may be
      inadequate. TLR agonists may augment the innate response and are being
      investigated.

PMID- 18071708
TI  - Constitutive expression of a meiotic recombination protein gene homolog,
      OsTOP6A1, from rice confers abiotic stress tolerance in transgenic Arabidopsis
      plants.
AB  - Plant productivity is greatly influenced by various environmental stresses, such
      as high salinity and drought. Earlier, we reported the isolation of topoisomerase
      6 homologs from rice and showed that over expression of OsTOP6A3 and OsTOP6B
      confers abiotic stress tolerance in transgenic Arabidopsis plants. In this study,
      we have assessed the function of nuclear-localized topoisomerase 6 subunit A
      homolog, OsTOP6A1, in transgenic Arabidopsis plants. The over expression of
      OsTOP6A1 in transgenic Arabidopsis plants driven by cauliflower mosaic virus-35S
      promoter resulted in pleiotropic effects on plant growth and development. The
      transgenic Arabidopsis plants showed reduced sensitivity to stress hormone,
      abscisic acid (ABA), and tolerance to high salinity and dehydration at the seed
      germination; seedling and adult stages as reflected by the percentage of
      germination, fresh weight of seedlings and leaf senescence assay, respectively.
      Concomitantly, the expression of many stress-responsive genes was enhanced under
      various stress conditions in transgenic Arabidopsis plants. Moreover, microarray
      analysis revealed that the expression of a large number of genes involved in
      various processes of plant growth and development and stress responses was
      altered in transgenic plants. Although AtSPO11-1, the homolog of OsTOP6A1 in
      Arabidopsis, has been implicated in meiotic recombination; the present study
      demonstrates possible additional role of OsTOP6A1 and provides an effective tool
      for engineering crop plants for tolerance to different environmental stresses.

PMID- 18071709
TI  - Volume doubling time and growth rate of renal cell carcinoma determined by
      helical CT: a single-institution experience.
AB  - The purpose of this study was to retrospectively evaluate the volume doubling
      time (VDT) and growth rate of renal cell carcinomas (RCC) on a serial computed
      tomography (CT) scan. Thirty pathologically proven RCCs were reviewed with
      helical CT. Each tumor underwent at least two CT scans. Tumor volume was
      determined using an area measuring tool and the summation-of-areas technique.
      Growth rate was evaluated in terms of diameter and volume changes. VDT and volume
      growth rate were compared in relation to several factors (initial diameter,
      initial volume, diameter growth rate, volume growth rate, tumor grade, tumor
      subtype, sex or age). Mean VDT of RCCs was 505 days. Mean diameter and volume
      growth rate were 0.59 cm/year and 19.1 cm(3)/year, respectively. For volume and
      diameter growth rate, tumors < or =4 cm showed lower rates than those >4 cm (P <
      0.01). VDT was weakly negatively correlated with diameter growth rate (P > 0.05).
      Volume growth rate was moderately to strongly positively correlated with initial
      diameter, initial volume and diameter growth rate (P < 0.05). In conclusion,
      small RCCs grew at a slow rate both diametrically and volumetrically. More
      accurate assessment of tumor growth rate and VDT may be helpful to understand the
      natural history of RCC.

PMID- 18071711
TI  - Prone positioning improves distribution of pulmonary perfusion: noninvasive
      magnetic resonance imaging study in healthy humans.
AB  - The purpose of this study was to evaluate the effects of prone positioning on
      pulmonary perfusion using flow-sensitive alternating inversion recovery (FAIR), a
      noninvasive magnetic resonance imaging technique that requires no contrast
      medium. Seven healthy volunteers were studied in the supine and prone positions
      under three respiratory conditions: normal breathing of room air, unassisted
      breathing of 45% O2, and controlled mechanical ventilation (CMV) with positive
      end-expiratory pressure. Signal intensities (SIs) were obtained from ventral,
      middle, and dorsal regions on sagittal lung images and dependent/nondependent SI
      ratios were calculated to evaluate pulmonary perfusion distribution. In the
      supine position, SIs increased significantly from the ventral to dorsal region
      under all three respiratory conditions and prone positioning inverted the
      perfusion distribution under all conditions. Right lung SI ratios were 2.34 +/-
      0.29, 2.74 +/- 0.66, and 2.42 +/- 0.73 in the supine position and 1.68 +/- 0.48,
      1.78 +/- 0.36, and 1.92 +/- 0.21 in prone for room air, 45% O2, and CMV,
      respectively. The difference between supine and prone positions was statistically
      significant. The left lung showed a similar pattern and the difference was
      significant only under CMV. No difference was observed between the different
      respiratory conditions in both lungs. This study demonstrated that the
      distribution of pulmonary perfusion was more uniform in prone than in the supine
      position.

PMID- 18071710
TI  - MR-guided endovascular interventions: a comprehensive review on techniques and
      applications.
AB  - The magnetic resonance (MR) guidance of endovascular interventions is probably
      one of the greatest challenges of clinical MR research. MR angiography is not
      only an imaging tool for the vasculature but can also simultaneously depict high
      tissue contrast, including the differentiation of the vascular wall and
      perivascular tissues, as well as vascular function. Several hurdles had to be
      overcome to allow MR guidance for endovascular interventions. MR hardware and
      sequence design had to be developed to achieve acceptable patient access and to
      allow real-time or near real-time imaging. The development of interventional
      devices, both applicable and safe for MR imaging (MRI), was also mandatory. The
      subject of this review is to summarize the latest developments in real-time MRI
      hardware, MRI, visualization tools, interventional devices, endovascular tracking
      techniques, actual applications and safety issues.

PMID- 18071712
TI  - Relative Wulst volume is correlated with orbit orientation and binocular visual
      field in birds.
AB  - In mammals, species with more frontally oriented orbits have broader binocular
      visual fields and relatively larger visual regions in the brain. Here, we test
      whether a similar pattern of correlated evolution is present in birds. Using both
      conventional statistics and modern comparative methods, we tested whether the
      relative size of the Wulst and optic tectum (TeO) were significantly correlated
      with orbit orientation, binocular visual field width and eye size in birds using
      a large, multi-species data set. In addition, we tested whether relative Wulst
      and TeO volumes were correlated with axial length of the eye. The relative size
      of the Wulst was significantly correlated with orbit orientation and the width of
      the binocular field such that species with more frontal orbits and broader
      binocular fields have relatively large Wulst volumes. Relative TeO volume,
      however, was not significant correlated with either variable. In addition, both
      relative Wulst and TeO volume were weakly correlated with relative axial length
      of the eye, but these were not corroborated by independent contrasts. Overall,
      our results indicate that relative Wulst volume reflects orbit orientation and
      possibly binocular visual field, but not eye size.

PMID- 18071713
TI  - Maturation of the contractile response of the Emu ductus arteriosus.
AB  - The avian embryo has a pair of ductus arteriosi that allow the blood to bypass
      the pulmonary circulation prior to the initiation of lung ventilation. Our
      objective was to characterize the factors regulating DA tone during the later
      stages of development in the emu embryo. We examined in vitro the reactivity of
      the emu ductus from day 39 through 49 of a 50-day incubation. Steady state
      tension was not altered by the COX inhibitor indomethacin or the nitric oxide
      synthase inhibitor L-NAME. However, prostaglandin E(2) (PGE(2)) produced a
      significant relaxation. Norephinephrine and U-46619 produced strong significant
      contractions in the emu DA and the adrenergic response matured with development.
      The contractile response to oxygen matured as the embryo developed with
      significant oxygen-induced contraction on days 45 and 49, but not on day 39 of
      incubation. The Kv channel inhibitor 4-aminopyridine induced the contraction of
      the day 48-49 ductus of similar magnitude as the oxygen-induced contraction. The
      oxygen-induced contraction was reversed by the reducing agent DTT and the
      electron transport chain inhibitor rotenone. These results suggest that while the
      emu DA responds to PGE(2), locally produced PGE(2) are not the important
      regulators of vessel tone. Additionally, relaxation upon addition of the
      mitochondria electron transport chain inhibitor rotenone suggests that the
      mitochondria might be acting as vascular oxygen sensors in this system through
      the production of reactive oxygen species to stimulate the oxygen-induced
      contraction in a similar fashion to mammals.

PMID- 18071714
TI  - Differences in cold tolerance, desiccation resistance, and cryoprotectant
      production between three populations of Eurosta solidaginis collected from
      different latitudes.
AB  - Possible links between cold-tolerance and desiccation resistance were examined
      between larvae of the goldenrod gall fly collected from Michigan, southern Ohio,
      and Alabama locations as their host plant senesced. After acclimation to 5
      degrees C, Michigan-collected larvae were more cold-tolerant (25% survival after
      a 96 h exposure to -40 degrees C) than larvae from Ohio (10% survival) and
      Alabama (0% survival). Increased cold-tolerance was partially linked to higher
      concentrations of the cryoprotectant glycerol (Michigan: 500 +/- 30 mmol; Ohio:
      270 +/- 20; Alabama: 220 +/- 20). Moreover, cryoprotectants may have functioned
      to reduce rates of overall and cuticular water loss for Michigan larvae, 0.10 +/-
      0.01 and 0.037 +/- 0.003 microg mm(-2) h(-1), respectively, values that were 40
      44% lower than those for Ohio and Alabama larvae and may represent a link between
      desiccation resistance and cold-tolerance. After acclimation to 20 degrees C,
      Alabama-collected larvae had metabolic rates that were 40% lower than those from
      Ohio and Michigan that averaged 0.100 +/- 0.006 microl of CO(2) produced g(-1) h(
      1). The lower metabolic rate of Alabama-collected larvae at 20 degrees C likely
      resulted in reduced respiratory transpiration that may represent a mechanism to
      maintain water balance at the higher overwintering temperatures they typically
      experience.

PMID- 18071715
TI  - Northern grass lizards (Takydromus septentrionalis) from different populations do
      not differ in thermal preference and thermal tolerance when acclimated under
      identical thermal conditions.
AB  - We acclimated adults of Takydromus septentrionalis (northern grass lizard) from
      four localities (populations) under identical thermal conditions to examine
      whether local thermal conditions have a fixed influence on thermal preference and
      thermal tolerance in the species. Selected body temperature (Tsel), critical
      thermal minimum (CTMin), and critical thermal maximum (CTMax) did not differ
      between sexes and among localities in lizards kept under identical laboratory
      conditions for approximately 5 months, and the interaction effects between sex
      and locality on these measures were not significant. Lizards acclimated to the
      three constant temperatures (20, 25, and 35 degrees C) differed in Tsel, CTMin,
      and CTMax. Tsel, CTMin, and CTMax all shifted upward as acclimation temperature
      increased, with Tsel shifting from 32.0 to 34.1 degrees C, CTMin from 4.9 to 8.0
      degrees C, and CTMax from 42.0 to 44.5 degrees C at the change-over of
      acclimation temperature from 20 to 35 degrees C. Lizards acclimated to the three
      constant temperatures also differed in the range of viable body temperatures; the
      range was widest in the 25 degrees C treatment (38.1 degrees C) and narrowest in
      the 35 degrees C treatment (36.5 degrees C), with the 20 degrees C treatment in
      between (37.2 degrees C). The results of this study show that local thermal
      conditions do not have a fixed influence on thermal preference and thermal
      tolerance in T. septentrionalis.

PMID- 18071716
TI  - Unusual causes of extrahepatic biliary obstruction in children: a case series
      with review of literature.
AB  - This paper highlights the etiology, diagnosis, management and outcome in nine
      unusual cases of extrahepatic biliary obstruction in children. Extrahepatic
      biliary atresia and choledochal cyst constituted 127 out of 136 (93%) cases of
      all pediatric surgical biliary disorders managed between March 2000 and February
      2007 at the reporting centre. However, nine children (aged 1.5-15 years)
      presented with uncommon causes like (1) idiopathic benign non-traumatic
      inflammatory stricture (n = 3), (2) idiopathic fibrosing chronic pancreatitis (n
      = 2), (3) post-cholecystectomy type 4 benign biliary stricture (n = 1), (4) post
      acute pancreatitis pseudo-cyst of pancreas (n = 1), (5) non-Hodgkin's lymphoma
      (NHL) with extramural common bile duct compression and gall bladder perforation
      (n = 1), and (6) Langerhan cell histiocytosis (LCH, n = 1). The clinical features
      and the diagnostic work up of each group are discussed. A preoperative
      endoscopic/percutaneous biliary drainage was required in four children because of
      cholangitis at presentation. A biliary-enteric anastomosis was performed for all
      seven children in groups (1)-(4). The patients with NHL and LCH were referred for
      chemotherapy after establishing tissue diagnosis at laparotomy. With a follow-up
      period of 3 months to 7 years, seven children (with the exception of patients
      with NHL and LCH) are currently anicteric. This paper draws attention to some
      infrequently discussed causes of extrahepatic biliary obstruction in children.
      The management entails a carefully planned combination of endoscopic
      interventions, interventional radiology and surgery. The outcome in benign cases
      is usually satisfactory.

PMID- 18071717
TI  - Congenital cardiovascular defects in children with intestinal malrotation.
AB  - Intestinal malrotation (IM) and cardiovascular defects (CCVD) are both common
      congenital defects. We investigated the prevalence and types of CCVD in a 25-year
      IM population, and its association with post-IM-operative morbidity and
      mortality. Data on the type of CCVD, other congenital defects, syndromes,
      associations, post-IM-operative morbidity and mortality were retrospectively
      reviewed from the records of IM patients born between 1980 and 2005. Data were
      analyzed on (significant) differences between CCVD subgroups, and risk factors
      for both morbidity and mortality were calculated. Seventy-seven of 284 IM
      patients (27.1%) were diagnosed with a major or minor CCVD (37 and 40 patients,
      respectively). Syndromes and associations were more frequently diagnosed in
      patients with major than with a minor CCVD (67.6 vs. 40%, respectively). Post-IM
      operative complications, although frequently observed (61%), did not differ
      between patients with major and minor CCVD. Physical CCVD signs before IM surgery
      increased post-IM-operative morbidity significantly (OR 4.0, 95% CI 1.4-11.0).
      Fifteen patients died (19.5%), seven due to cardiovascular cause. Mortality risk
      was increased by intestinal ischemia and post-IM-operative complications and by
      major CCVD after correction for age at weight at the time of IM operation.
      Congenital cardiovascular defects in children with intestinal malrotation are
      common, with high morbidity and mortality rates after IM operation. Elective IM
      surgery in young patients with CCVD should be performed in a centre with adequate
      paediatric cardiac care. Benefits of laparoscopic intervention need further
      study.

PMID- 18071718
TI  - Role of cyanoacrylate in the management of low fistula in ano: a prospective
      study.
AB  - BACKGROUND AND AIMS: Fistulotomy has remained the gold standard in the management
      of fistula in ano, especially low fistula in ano. Although highly effective in
      the management of fistula in ano, fistulotomy is associated with considerable
      discomfort and incontinence. This study was designed to evaluate the role of
      cyanoacrylate in the management of low fistula in ano. We present our short-term
      results with a 6-month follow-up. MATERIALS AND METHODS: Twenty patients were
      enrolled in the study as day cases. Patients were analyzed clinically and then
      subjected to trans-anal ultrasound, as diagnosis of internal opening was not
      palpable on per rectal examination. The fistula tracks were probed and washed
      with saline, and granulation tissue at external opening was debrided. The glue
      was then injected into the fistulous track from a syringe nozzle through an
      infant feeding tube. Patients were further examined in the outpatient department
      until 6 months. RESULTS: Seventeen patients got healed with primary injection
      with stoppage of any discharge from the fistulous track. The other two patients
      required one more injection and showed no signs of discharge thereafter. One
      patient who had two external openings continued to discharge from one opening
      even after two injections. CONCLUSIONS: Cyanoacrylate glue can be offered as an
      effective alternative to surgery in patients suffering from fistula in ano as it
      is easy, safe, non-invasive, and effective.

PMID- 18071719
TI  - Safety and morbidity after ultra-low coloanal anastomoses: J-pouch vs end-to-end
      reconstruction.
AB  - BACKGROUND AND AIMS: Anastomotic failure after ultra-low anterior rectum
      resection is the most important complication, and it is influenced by the type of
      reconstruction. The aim of this study was to compare retrospectively the straight
      coloanal anastomosis with the J-pouch reconstruction concerning the development
      of anastomotic leakage. MATERIALS AND METHODS: Fifty-six of 381 consecutive
      patients underwent low anterior rectum resection with total mesorectal excision
      and ultra-low coloanal anastomosis at 3-4 cm from the anocutan line. A 5-cm J
      pouch (side-to-end) was performed in 25, a straight coloanal anastomosis in 25,
      and a coloplasty in 6 patients, respectively. RESULTS/FINDINGS: No influence by
      age, body mass index, and operating time on anastomotic leakage rate was found.
      Leakage was found in eight patients with straight coloanal anastomosis, resulting
      in a leakage rate of 32% compared to one patient in the J-pouch group (P =
      0.023). INTERPRETATION/CONCLUSION: Patient's safety is higher after J-pouch
      reconstruction because of the lower anastomotic failure rate, and functional
      results had been reported as similar after J-pouch reconstruction and straight
      coloanal anastomosis. Therefore, we clearly argue for a J-pouch reconstruction as
      the standard method after ultra-low coloanal anastomosis.

PMID- 18071720
TI  - Tumor response to neoadjuvant chemoradiation in rectal cancer: predictor for
      surgical morbidity?
AB  - BACKGROUND: Increasing the rate of pathological complete remissions after
      neoadjuvant chemoradiation of rectal cancer has become a strategy to further
      improve the long-term oncological outcome of patients. This report evaluates the
      influence of preoperative intensified radiochemotherapy on the rate and outcome
      of surgical complications. MATERIALS AND METHODS: Patients with primary rectal
      cancer at stages cT3/4cNx or N+ without metastasis were preoperatively treated
      either with capecitabine and irinotecan or with capecitabine, irinotecan and
      ceutximab with a concurrent radiation (50.4 Gy). Surgery was scheduled 4-7 weeks
      after completion of the chemoradiation. Perioperative complications were
      prospectively documented during the patient's hospital stay. RESULTS: Fifty-nine
      patients (median age 60; male/female: 46/13) undergoing surgery at a single
      center were analysed. The median distance of the tumour from the dentate line was
      5 cm. The operations performed were low anterior resection (n=45), Hartmann's
      procedure (n=4) and abdominoperineal resection (n=10). Total mesorectal excision
      with R0-resection was accomplished in all but one patients. Histopathological
      regression was described in four grades (0-3) as defined by the Japanese Society
      for Cancer of the Colon and Rectum. Tumors were called major responsive when
      assigned to the regression grades 3 or 2, and minor or nonresponsive at
      regression grades 1 or 0. In total, 33 patients (55.9%) had a regression grade 2
      or 3. Among them, 12 patients showed a pathological complete response without any
      residual cancer cell (20.3%). Seven out of 45 patients (15.5%) with sphincter
      preserving surgery suffered from suture breakdown; they all had previously shown
      a major response of the resected tumor. Two of them died during the hospital
      stay. CONCLUSIONS: While in general, patients undergoing neoadjuvant intensified
      treatment suffer from a slight increase in surgical complications, this is
      markedly enhanced in patients with good treatment responses. Our results
      underline the oncological benefit of intensified neoadjuvant chemoradiation, but
      the severity of complications in low rectal anastomosis of patients with good
      response after neoadjuvant therapy should alert surgeons and oncologists.

PMID- 18071722
TI  - Acta Neuropathologica and their case reports.

PMID- 18071721
TI  - Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFalpha,
      improves health-related quality of life in patients with moderate to severe
      Crohn's disease.
AB  - BACKGROUND AND AIMS: Certolizumab pegol, a polyethylene glycolated Fc-free Fab'
      was efficacious and well tolerated in patients with moderate-to-severe Crohn's
      disease in a previously reported randomized, placebo-controlled study. In this
      paper, we report the effect of certolizumab pegol on health-related quality of
      life (HRQoL). MATERIALS AND METHODS: Patients with moderate-to-severe active
      Crohn's disease (n = 292) received subcutaneous certolizumab pegol 100, 200, or
      400 mg or placebo at weeks 0, 4, and 8. A post hoc analysis of the intent-to
      treat population (290 patients with HRQoL data) assessed HRQoL by evaluating
      patients' responses to the self-administered inflammatory bowel disease
      questionnaire (IBDQ) at baseline and weeks 2, 4, 6, 8, 10, and 12. RESULTS:
      Patients receiving certolizumab pegol 400 mg at weeks 0, 4, and 8 demonstrated,
      via their IBDQ total score, significantly (P <or= 0.05) greater improvement in
      HRQoL from baseline to week 12 and at all other time points compared with
      placebo. Moreover, HRQoL improved over time in all certolizumab pegol groups,
      irrespective of baseline C-reactive protein levels. Emotional well-being (IBDQ
      Emotional Function domain) improved throughout the study for patients receiving
      certolizumab pegol 400 mg. This improvement was significantly (P <or= 0.05)
      greater than for patients receiving placebo at all time points. In addition,
      systemic symptoms (IBDQ Systemic Symptoms domain) improved significantly more in
      patients receiving certolizumab pegol 400 mg than in those receiving placebo at
      weeks 4, 8, 10, and 12 (P <or= 0.05) and approached statistical significance at
      week 2 (P = 0.054). CONCLUSION: This analysis suggests that certolizumab pegol
      400 mg improves HRQoL in patients with moderate-to-severe Crohn's disease.

PMID- 18071723
TI  - Intraoperative navigation in hip surface arthroplasty: a radiographic comparative
      analysis study.
AB  - BACKGROUND: The goal of the current prospective randomised radiological study was
      to determine the accuracy of conventional and computer-assisted femoral component
      implantation in surface arthroplasty (SRA). METHODS: We analysed on standard
      radiographs the femoral component positions after 30 conventional instrumented
      (Group 1) and 30 navigated (Group 2) SRA femoral components. We evaluated: varus
      or valgus orientation, horizontal femoral offset and translation of the
      component. RESULTS: The tendency to implant the femoral component in mild valgus
      position (2.8 degrees in Group 1 compared to 2.1 degrees in Group 2), more
      distally and ventrally in the femoral neck (in Group 1) and with femoral off-set
      increase (4.8 mm in Group 1 compared to 3.4 mm in Group 2) was found.
      CONCLUSIONS: The navigation system enables a more accurate insertion of the
      femoral component.

PMID- 18071724
TI  - Parthenolide-depleted Feverfew (Tanacetum parthenium) protects skin from UV
      irradiation and external aggression.
AB  - The skin is under continual assault from a variety of damaging environmental
      factors such as ultraviolet irradiation and atmospheric pollutants, and as
      organisms age the cumulative damage exceeds the capacity of endogenous
      antioxidant defenses resulting in chronic inflammation and premature aging.
      Botanical extracts such as Feverfew containing naturally occurring antioxidants
      could replenish the depleted cutaneous stores and perhaps forestall these
      degenerative changes. A parthenolide-depleted extract of Feverfew (PD-Feverfew),
      which was free of sensitization potential, was found to possess free radical
      scavenging activity against a wide range of reactive oxygen species and with
      greater activity than Vitamin C. In vitro, PD-Feverfew restored cigarette smoke
      mediated depletion of cellular thiols, attenuated the formation of UV-induced
      hydrogen peroxide and reduced pro-inflammatory cytokine release. In vivo, topical
      PD-Feverfew reduced UV-induced epidermal hyperplasia, DNA damage and apoptosis.
      In a clinical study PD-Feverfew treatment significantly reduced erythema versus
      placebo 24 h post-UV exposure. Through the ability to scavenge free radicals,
      preserve endogenous antioxidant levels, reduce DNA damage and induce DNA repair
      enzymes, which can help repair damaged DNA, parthenolide-depleted extract of
      Feverfew may protect skin from the numerous external aggressions encountered
      daily by the skin and reduce the damage to oxidatively challenged skin.

PMID- 18071725
TI  - A study of the pathogenesis of rosacea: how angiogenesis and mast cells may
      participate in a complex multifactorial process.
AB  - In the present study we evaluated, in involved and clinically uninvolved skin of
      Rosacea, microvessels density (MVD) and total vascular area (TVA) in addition to
      multiple morphologic characteristics of microvessels and also mast cells (MCs)
      number. We examined also the relationship between angiogenesis, MCs number and
      disease clinicopathological data. The study included 69 patients with Rosacea. A
      skin biopsy with a 4-mm punch was performed from clinically involved skin in each
      case. In nine randomly selected patients, facial biopsy specimens were obtained
      from both involved and clinically uninvolved skin. Histological sections,
      immunostained for factor VIII, were evaluated by image analysis for the
      quantification of MVD, TVA and several morphometric parameters related to the
      vessel size or shape. MCs detection in the dermis was carried out using the
      chloracetate esterase method (Fast Blue RR) in parafin sections. Serum antibodies
      against H.pylori were detected. Statistically important differences concerning
      the factors of angiogenesis between lesional and clinically non-lesional skin
      were demonstrated. A statistical important correlation was found also between
      high vascular density, PPR clinical type and the presence of ocular
      manifestations. MVD or TVA showed no correlation with the degree of solar
      elastosis or inflammation and with the Demodex density as well. However, high MVD
      values were found to correlate with granuloma formation in the dermis. MCs number
      were significantly greater in lesional compared to clinically non-lesional skin.
      Statistical significance was shown between MCs density and disease duration.
      However, no correlation between MCs number and blood vessel density was found.
      Angiogenesis seems to play an important role in the pathogenesis especially of
      the more severe clinical form of Rosacea. MCs seem to participate in evolution to
      disease chronicity by contributing to inflammation, angiogenesis and tissue
      fibrosis.

PMID- 18071726
TI  - Prevention of cerebral palsy during labour: role of foetal lactate.
AB  - OBJECTIVES: Intrapartum foetal monitoring goal is to prevent foetal asphyxia and
      its most severe consequence: cerebral palsy (CP). In this paper we describe the
      detection methods and the criteria needed to assess asphyxia during labour for
      preventing CP. Foetal cerebral damage assessment is considered from the medical
      legal point of view. CP represents the most frequent pathology of childhood
      related to pregnancy and childbirth with an incidence of 0.2% in children born
      alive. It is clinically regarded as the result of a spectrum of diseases due to
      damage or to faded development of the nervous system which generally appears at
      the time of the first stage of intra-uterine growth or depends on problems
      arising at birth. The goal of our analysis is to recall the various moments in
      which this event can take place and, if possible, the moment and the degree of
      the event of asphyxia and its effect on foetal conditions, in order to control
      and treat it. STUDY DESIGN: One hundred and eighty-eight fetuses were evaluated
      by means of Apgar score, intrapartum cardiotocography, observation of the
      presence of meconium stained amniotic fluid, and clinical features of distress at
      birth. Lactate concentrations were measured during labour and at delivery in
      blood samples obtained from the foetal presenting part (foetal scalp) and from
      the umbilical cord with the use of a rapid electrochemical technique. RESULTS:
      Evidence of clinical foetal distress was not related to the severity of asphyxia.
      An increased lactate level was found in asphyctic infants and a clear correlation
      between lactic acidosis and foetal distress was documented. Low Apgar scores were
      observed in infants with moderate or severe asphyxia at delivery. Scalp lactate
      correlated significantly with umbilical artery lactate (P = 0.49, 0.01), but with
      neither Apgar score at 1 min (R = -0.21, ns) nor at 5 min (R = -0.11, ns).
      Lactate concentration was higher in case of instrumental delivery compared to
      spontaneous delivery (P = 0.0001). No perfect correlation was found between
      lactate level and neonatal outcome, but there were not a significant number of
      neonates with immediate complications. The rate of instrumental delivery in the
      distress group was significantly higher than in that of the healthy fetuses (P <
      0.01), so spontaneous labour was less frequently associated with foetal distress
      than instrumental delivery (P < 0.01). In the distress group, severe variable
      decelerations were generally recorded in the second stage of labour. The
      incidence of neonatal Apgar score </=7 in neonates with abnormal baseline foetal
      heart rate (FHR) was higher than in those with severe variable decelerations,
      mild variable decelerations, and transient tachycardia (P < 0.05). The duration
      of the active second stage of labour correlated significantly with the presence
      of foetal lactate (P < 0.001) at the time of crowning of foetal head, and the
      presence of lactate in umbilical cord blood at delivery (P < 0.001). Expulsion
      time >/=45 min, compared with a shorter active second stage, and acidaemia at
      birth implied larger arterial-venous lactate differences (P < 0.001). The
      presence of foetal lactate at crowning was also significantly associated with the
      level of umbilical arterial-venous lactate difference (P = 0.03). CONCLUSIONS:
      Analysis of the fetus should start with the assessment of lactates and acid-base
      balance. The method which revolutionized the techniques of foetal monitoring is
      undoubtedly represented by cardiotocography. However, likely most of neurological
      outcomes are not correlated with a perinatal event or with peripartum asphyxia.
      Approximately 10% of cases of CP would actually be due to perinatal asphyxia, and
      this percentage approaches approximately to 15% if we consider only newborns at
      term. This again confirms the weak association of a causal relationship between
      asphyxia and CP. In addition, available foetal suffering markers are vague and
      allow to identify only less than half of the effective cases of newborns which
      will develop CP.

PMID- 18071727
TI  - Treatment options and pregnancy outcome in women with idiopathic recurrent
      miscarriage: a randomized placebo-controlled study.
AB  - OBJECTIVE: To compare the use of enoxaparin alone with combination therapy of
      prednisone, aspirin and progesterone in the treatment of women with idiopathic
      recurrent miscarriage (IRM) in terms of live births and pregnancy outcome.
      METHODS: A prospective, randomized, single-blinded, placebo-controlled trial was
      conducted at a tertiary referral obstetric hospital. The participants were 170
      women with a diagnosis of IRM. Women were recruited after full investigative
      screening. Women with > or =3 fetal losses and after exclusion of all known
      causes of recurrent miscarriage were randomly allocated to receive either
      enoxaparin alone, combination treatment consisting of prednisone, aspirin, and
      progesterone or placebo. Rates of live births, antenatal complications, delivery
      and neonatal outcomes were recorded prospectively. Data were statistically
      analyzed as appropriate. RESULTS: Ten patients were dropped out after random
      assignment. Eighty-one percent of the enoxaparin (46/57) group and 85% of the
      combination-treated group (45/53) were delivered of live infants compared to 48%
      (24/50) of the placebo (P < 0.05). Women who were treated with combination
      therapy had a 4.2% higher live birth rate than enoxaparin group. This difference
      was not significant. Miscarriage rates were significantly lower in the treated
      groups compared with placebo (P < 0.05). There were no significant differences in
      late obstetric complications or neonatal mortality between groups. CONCLUSIONS: A
      combination treatment consisting of high-dose, low-duration prednisone,
      progesterone and aspirin might be an effective treatment as enoxaparin alone.
      Both regimens were associated with a good pregnancy outcome.

PMID- 18071728
TI  - Prepregnancy body mass index and adverse pregnancy outcomes.
AB  - OBJECTIVE: The aim of this study was to evaluate the association between
      prepregnancy BMI, and adverse maternal and neonatal outcomes. METHOD: In this
      retrospective cohort study 916 consecutive singleton gestations were included who
      gave birth between 1 January 2006 and 31 August 2006 at the Department of
      Obstetrics and Gynecology, University of Udine, Italy. Statistical analysis was
      performed using univaried logistic regression and measured by odds ratio.
      RESULTS: The obese patients had a statistically, significantly increased
      incidence of Caesarean section (OR = 2.17, p = 0.009). Women with overweight (OR
      = 2.43, p = 0.002) and obese weight (OR = 4.86, p < 0.0001) were at increased
      risk for preterm deliveries. The pre-eclampsia and the fetal macrosomia (> or
      =4,000 g) were increased in obese women (OR = 5.68, p < 0.0001; OR = 2.58, p =
      0.033, respectively). CONCLUSION: Maternal prepregnancy obesity is significantly
      associated with increased risk of Caesarean section, preterm delivery, pre
      eclampsia and macrosomia.

PMID- 18071729
TI  - Systematic review of experimental studies on the relative biological
      effectiveness of tritium.
AB  - Tritium ((3)H) is a radioactive isotope of hydrogen. A number of factors combine
      to create a good deal of interest in tritium doses, both to workers and to
      members of the public. Tritium is ubiquitous in environmental and biological
      systems and is very mobile due to its occurrence as water. In this study we
      systematically review experimental data relating to tritium exposure with a view
      to assessing its low dose limiting relative biological effectiveness (RBE(max)).
      Interpretation of published experimental studies is complicated by the fact that
      the reference radiations varied, and doses and dose rates were frequently much
      higher than those normally received by humans. The four available animal
      carcinogenicity studies gave RBE values of about 2.5 with chronically-delivered
      gamma-ray reference, and about 1.2 with chronically-delivered X-ray reference.
      However, because of problems associated with the design and interpretation of the
      experiments, we do not consider that these RBE values should be taken to apply to
      the induction of cancer at low doses (i.e. they should not be interpreted as
      RBE(max)). Combining the six studies with chronic gamma-ray reference, with
      adequate quantitative data that examined endpoints apart from cell survival and
      related endpoints, yields an aggregate RBE estimate of 2.19 (95% CI 2.04, 2.33);
      the analogous combined RBE estimate using the three studies with chronic X-ray
      reference groups is 1.17 (95% CI 0.96, 1.39). Again, problems with the design, in
      particular the range of doses used in some of these studies, mean that these RBE
      values should also probably not be interpreted as RBE(max).

PMID- 18071730
TI  - Long-term results of amniotic membrane transplantation-assisted bleb revision for
      leaking blebs.
AB  - BACKGROUND: To report long-term results of amniotic membrane transplantation
      (AMT)-assisted bleb revision for intractable late-onset bleb leak. METHODS:
      Retrospective medical record review of six consecutive patients who underwent AMT
      assisted bleb revision for late-onset bleb leak at the Kobe University hospital
      between December 2001 and March 2004. RESULTS: The median (range) of age was 60
      (20-77) years. All patients had a history of trabeculectomy with adjunctive use
      of 0.4 mg/ml mitomycin C. The median (range) of interval between the prior
      trabeculectomy and bleb leak was 15 (4-54) months. Preoperative intraocular
      pressure (IOP) was lower than 10 mmHg in two cases, while it was 25 mmHg or
      higher in three patients, who had a localized, ischemic, thin-wall leaking bleb
      circumscribed with extensively scarred tissue. The median (range) of follow-up
      after the AMT-assisted bleb revision was 49 (41-67) months. Postoperative IOP was
      well controlled in all patients without medication or with a maximum of three
      glaucoma medications. No patients presented recurrence of the bleb leak or AMT
      related complications during entire follow-up. All patients showed at final visit
      a diffuse bleb which extended posteriorly beyond the conjunctival incision line.
      CONCLUSION: AMT-assisted bleb revision successfully treated intractable late
      onset bleb leak. Further comparative studies are needed to confirm the present
      result.

PMID- 18071731
TI  - Time-dependent effects on contrast sensitivity, near and distance acuity:
      difference in functional parameters? (Prospective, randomized pilot trial of
      photodynamic therapy versus full macular translocation).
AB  - PURPOSE: To report the change of contrast sensitivity (CS) after photodynamic
      therapy (PDT) vs full macular translocation (FMT) for neovascular age-related
      macular degeneration (AMD), and to relate this to other measures of visual
      function (distance and near acuity). METHODS: Fifty patients (50 eyes) with
      predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to
      AMD were randomized to PDT or FMT. CS was measured with Pelli-Robson charts.
      Acuity scores of near visual function (NVS) were calculated after testing with
      visual acuity cards of the Swiss National Association of and for the Blind
      (SNAB). Best corrected distance visual acuity (DVA) was determined according to a
      standardized protocol with EDTRS charts. Primary end point was the change of CS
      at 12-month examination from baseline. The interaction of the CS with NVS and DVA
      was analysed. RESULTS: Mean CS showed a decrease in both treatment groups (FMT: 
      2 letters, PDT: -3 letters, p=0.969) at 12-month examination from baseline. While
      mean NVS improved by seven letters in the FMT group, a decrease of more than ten
      letters was seen in the PDT group (p<0.05). We found no agreement between CS and
      high-contrast acuity (NVS, DVA). In FMT patients, the parameters at baseline (CS,
      NVS, DVA) correlated poorly with the corresponding 12-month results, therefore
      providing no informative basis to predict the later functional development. In
      contrast, PDT patients showed strong baseline-to-outcome coherence with baseline
      measures also associated with better final values. CONCLUSIONS: Although FMT can
      initiate recovery of near and distance acuity over the period of 1 year in
      selected patients with classic CNV, CS did not differ between FMT and PDT. We
      found no close connection of CS with DVA or NVS, especially after FMT. Knowledge
      about the unequal variation of visual parameters can provide more comprehensive
      information when advising patients on different therapeutic options. That also
      applies in particular to vascular endothelial growth factor inhibitors, which
      seem to promise an even higher extent of gain in CS and to reach the peak of
      recovery at an earlier time.

PMID- 18071732
TI  - Visual outcome after vitreous, sub-internal limiting membrane, and/or submacular
      hemorrhage removal associated with ruptured retinal arterial macroaneurysms.
AB  - BACKGROUND: Ruptured retinal arterial macroaneurysms (RAM) can bleed into the
      various spaces of the eye. The hemorrhage of the inner layer conceals hemorrhage
      of the outer layer, making it difficult to diagnose the distribution of
      hemorrhage accurately and to predict the prognosis in clinical examinations. The
      objective of this study was to examine the clinical features and prognosis of
      ruptured RAM on the basis of surgical observations. METHODS: Retrospective review
      of 33 eyes of 31 patients with impairment of visual acuity due to hemorrhage from
      a ruptured RAM, who had undergone pars plana vitrectomy. A study of the location
      of hemorrhage was made from the preoperative fundus photographs and video of the
      surgical procedure. RESULTS: Hemorrhage from the RAM was present in two or more
      locations, consisting of the vitreous cavity, beneath the internal limiting
      membrane (sub-ILM), or the subretinal space in all but one eye. Sub-ILM
      hemorrhage was presented in the macular region in 22 of the 27 eyes presenting
      with sub-ILM hemorrhage (81%). Submacular hemorrhage was only detected when sub
      ILM hemorrhage removed during surgery in 12 of the 22 eyes (55%) with sub-ILM
      hemorrhage. The preoperative VA ranged from hand motion to 0.1, while
      postoperative VA improved 0.01 to 1.0 (average: 0.2, paired t-test, P<0.01). The
      VA was poor in eyes with dense submacular hemorrhage, while it was good in eyes
      with other hemorrhage. CONCLUSIONS: The effects of vitrectomy were influenced by
      the location of hemorrhage from the RAM. The VA was poor in eyes exhibiting dense
      submacular hemorrhage. However, since hemorrhage from a RAM was present at
      various levels within the eye, it was difficult to evaluate the amount of
      submacular hemorrhage prior to surgery.

PMID- 18071733
TI  - Pattern of ocular trauma in Egypt.
AB  - PURPOSE: To review the epidemiology of serious ocular trauma presenting to Kasr
      El Aini Hospital, Cairo University. METHODS: This is a prospective
      epidemiological and clinical study of ocular trauma patients admitted to Kasr El
      Aini hospital during a 6-month period; January-June 2000. Cases were analyzed
      with respect to: (1) demographics, (2) time, place and nature of trauma, (3) type
      of injury, (4) time to receive care, and (5) management and visual outcomes
      following primary repair. RESULTS: One hundred and fifty three eyes of 147
      patients (six bilateral injuries) sustaining serious ocular injury requiring
      hospitalization were included during the study period. Eighty percent of ocular
      trauma occurred in men (P < 0.001 chi-square test) with an average age of 22
      years (ranging from 2 months to 76 years). There were 123 (80.4%) open globe
      injuries and 30 (19.6%) closed globe injuries. Of the open globe injuries, 48
      eyes (31.4% of all eyes) were ruptured globes and 75 eyes (49% of all eyes) were
      lacerated globes (37 intraocular foreign bodies, 35 penetrating injuries and
      three perforating injuries, that is 24%, 23%, and 2% respectively of all injured
      eyes). Of the closed globe injuries, 5.9% had hyphema (33% of all patients), 4%
      lamellar lacerations, and 2.5% vitreous hemorrhage with retinal detachment. Most
      of the injuries occurred (39.5%) and presented (36.7%) between 12:00-5:59 PM: .
      Eighteen patients (12%) presented after 24 hours, and nine patients (6%) 1 week
      after the time of trauma. Presenting visual acuity in 123 patients (123 eyes) was
      as follows: 98 (80%), ten (8%) and 15 (12%) patients had poor, moderate and good
      visual acuity respectively. Ten eyes developed posttraumatic endophthalmitis (8%
      of open globe injuries). On leaving the hospital, 77.1% eyes had a visual acuity
      of less then 1/60 (poor), 3.9% were between 1/60 and 6/60 (moderate), and 19%
      were 6/36 and/or better (good). Fifty-two (35%) patients were lost in follow-up:
      at 1 month, 60%, 7% and 33% of the rest had poor, moderate and good visual acuity
      respectively. CONCLUSION: The majority of ocular trauma in our population was due
      to assaultive injuries occurring mainly in males. Open globe injuries were more
      common than closed globe injuries, and globe lacerations were more common than
      ruptured globes. Open globe injuries, especially ruptured globes, had the worst
      visual outcomes. The initial visual acuity correlated well with the final visual
      acuity. Immediate and comprehensive medical care is mandatory for ocular trauma
      patients. Educating the public is essential if we wish to prevent eye injuries.

PMID- 18071734
TI  - Antifungal chemotherapy for fungal keratitis guided by in vivo confocal
      microscopy.
AB  - BACKGROUND: To evaluate antifungal chemotherapy in patients with fungal keratitis
      guided by in vivo confocal microscopy. METHODS: A total of 121 patients (121
      eyes) with fungal keratitis were enrolled in this study. Confocal microscopy was
      performed in real time after topical and/or oral antifungal chemotherapy. Hyphal
      density and morphology, composition of inflammatory cells, and appearance of
      corneal stromal cells at the central and peripheral corneal lesions were
      recorded. Antifungal therapy discontinued at 1 week after hyphae and inflammatory
      cells could not be detected, and affected corneal stromal cells became visible.
      RESULTS: Successful outcomes were achieved in 110 patients (90.9%). By confocal
      microscopy, we observed the gradual decrease of hyphae-positive sites and hyphal
      density during the chemotherapy. The inflammatory cells reduced in number and
      heterogeneity, while corneal stromal cells recovered. The antifungal drugs were
      tapered according to the changes in hyphae, inflammatory cells, and corneal
      stromal cells. There was no fungal recurrence during the 2-month follow-up
      period. The other 11 patients (9.1%) had deteriorated infection within 1 week of
      antifungal therapy, and therefore were subjected to corneal transplantation.
      CONCLUSIONS: In vivo confocal microscopy appears to be an effective approach to
      guide antifungal chemotherapy. It allows comprehensive evaluation of hyphae,
      inflammatory cells, and corneal stromal cells in real time, and provides valuable
      and objective information required in selecting and adjusting therapeutic
      regimens for the treatment of fungal keratitis.

PMID- 18071735
TI  - Subretinal injection of preservative-free triamcinolone acetonide and supernatant
      vehicle in rabbits: an electron microscopy study.
AB  - BACKGROUND: To evaluate the effect of injections of benzyl alcohol (BA)-free
      triamcinolone acetonide (TA) solution (MTA-PF) and the supernatant vehicle of TA
      (STA) containing BA into the subretinal space of rabbit eyes. METHODS: Sixteen
      rabbits underwent vitrectomy and subretinal injection of 0.02 ml of either 40
      mg/ml MTA-PF, 40 mg/ml STA, or balanced salt solution (BSS). The animals were
      examined 6, 12, and 24 hours and 14 days after the procedure by fundus
      examination and fluorescein angiography (FA), as well as histological studies by
      light and transmission electron microscopy. The histological injury was
      classified in four stages: (1) stage 1, photoreceptor outer segment injury, (2)
      stage 2, stage 1 + photoreceptor inner segment injury, (3) stage 3, stage 2 +
      outer nuclear layer damage, and (4) stage 4, stage 3 + retinal pigment epithelium
      (RPE) damage. RESULTS: FA showed no window defects in areas where MTA-PF, STA, or
      BSS have been injected. Histological examination revealed that subretinal BSS
      injection resulted in stage 1 damage during entire follow-up. Subretinal
      injection of MTA-PF resulted in damage stage 2 at 24 h and 14 days after surgery.
      However, at the STA position, stage 3 damage was noted 24 h and 14 days
      postoperatively. No RPE or choroidal damage was observed. CONCLUSIONS: The
      histological lesions induced by subretinal STA were more relevant than the damage
      induced by MTA-PF. The vehicle BA may be involved in these abnormalities. The
      data indicate that care must be taken when using TA during internal limiting
      membrane peeling in macular hole surgery, due to the possibility of unintentional
      subretinal migration and for retinal pharmacotherapy.

PMID- 18071736
TI  - Intraocular pressure rise during 25-gauge vitrectomy trocar placement.
AB  - PURPOSE: Small-gauge vitrectomy has been used to treat various vitreous and
      macular pathologies. Trocar/cannula insertion may raise intraocular pressure
      (IOP) to the point it might become detrimental to the eye, especially in the
      setting of open-globe trauma and eyes with severe vascular compromise. We propose
      to determine the magnitude of this IOP rise and its possible implications.
      METHODS: Three different settings were designed to measure IOP rise during trocar
      placement for 25 ga vitrectomy (TSV); water-column manometry was performed during
      trocar placement in pig eyes. Electronic applanation tonometry was recorded in
      human eyes undergoing 25-ga vitrectomy for macular pathology during trocar
      placement, and wound behavior was recorded during trocar placement in harvested
      dog eyes with a previously sutured corneal wound. RESULTS: The pressure recorded
      during trocar placement was 57.5 mmHg in pig eyes and 63.7 mmHg in human eyes.
      Sutured corneal wounds in dog eyes showed wound leakage and tissue incarceration
      during trocar insertion. CONCLUSIONS: The 25-ga vitrectomy system may have
      limited usefulness in the setting of open-eye trauma and compromised bloodflow,
      due to the elevated pressures reached during trocar placement.

PMID- 18071737
TI  - Comment on the recent publication "Conjunctival nodules associated with Vogt
      Koyanagi-Harada disease".

PMID- 18071739
TI  - Anterior chamber paracentesis in patients with acute elevation of intraocular
      pressure.

PMID- 18071740
TI  - The value of vision.
AB  - BACKGROUND: The value of vision is assumed to be very high. To verify this
      assumption and to assign resources in medical care accordingly, it is necessary
      to quantify the value of vision. Although the value of vision is difficult to
      measure, visual quality of life can be quantified as a surrogate criterion. The
      measured value gains even more relevance if a comparison can be made between
      visual quality of life and systemic diseases. Multidisciplinary comparisons are
      only possible by using utility analysis. Two established methods to measure
      utility values are the standard gamble method and the time trade-off method. The
      purpose of this review is to find ophthalmologic utility values, and utility
      values affected by systemic diseases that correlate to the ophthalmologic ones.
      METHODS: A literature search was conducted through PubMed of the National Library
      of Medicine ( http://www.ncbi.nlm.nih.gov ; date: 06.02.2006). The search terms
      were: "time trade-off / standard gamble" [text word] and "eye / vision / visual"
      [text word]; results 24. A report was classified as relevant if visually impaired
      persons were tested by the time trade-off method or the standard gamble method,
      or if information was provided on the reliability and validity of these
      measurements in a group of visually impaired persons. Additional searches were
      done to find associated publications. A total of 42 publications were found to be
      of interest. RESULTS: Results showed that patients, with 20/30-20/50 visual
      acuity would be willing to pay 19% of their lifetime to get back normal visual
      acuity. Patients with 20/200-20/400 visual acuity would give up 48% of their
      lifetime, and blind people would give 60% of their lifetime to regain normal
      visual acuity. Comparable utility values are seen in patients with AIDS (21%),
      patients after a stroke who are unable to walk and wash themselves without
      assistance (46%), and bedridden and incontinent patients following a stroke
      (66%). CONCLUSION: Patients attach great value to vision. The time trade-off
      method appears to be an appropriate tool to quantify visual quality of life, and
      one that can be used to compare utility values of different diseases.

PMID- 18071741
TI  - Retrospective exposure assessment for respirable and inhalable dust, crystalline
      silica and arsenic in the former German uranium mines of SAG/SDAG Wismut.
AB  - OBJECTIVES: Starting shortly after the reunification of Germany and lasting up to
      the end of the 1990s, an extensive series of retrospective exposure
      investigations for the East German uranium mining industry was performed in order
      to provide information about the exposure situation of the miners towards
      respirable dust, inhalable dust, crystalline silica and heavy metals. It should
      provide the necessary information for legal compensation of miners with potential
      industrial diseases as well as for epidemiological research. METHODS: Extensive
      side-by-side measurements using original historic equipments as well as
      comprehensive evaluation of the time increments of specific jobs with respect to
      exposure relevant tasks were performed. After attributing average exposures to
      the tasks, shift exposures for the jobs could be calculated. RESULTS: By the end
      a comprehensive job exposure matrix for all underground jobs of the German
      uranium mining industry was developed for the components mentioned, including
      arsenic where relevant. In the early days of SAG/SDAG Wismut dust and silica
      exposures were extremely high with respirable dust up to 20 mg/m(3) and
      respirable crystalline silica well above 2 mg/m(3) as shift averages. Beginning
      from about the early 1960s dust control measures started to improve conditions
      dramatically. CONCLUSIONS: It is absolutely necessary to invest sufficient effort
      for the estimation of exposure situations of past technological environments.
      Especially, the situation of early mechanised mining, characterised by low
      ventilation, dry drilling techniques and generally lacking dust control measures
      was characterized by extreme shift exposures. It is important to keep these in
      mind when metal mining exposure in different environments is considered.

PMID- 18071742
TI  - Strength training improves supramaximal cycling but not anaerobic capacity.
AB  - This study examined supramaximal cycling performed to exhaustion at 120% of peak
      O(2) uptake (120% VO(2)peak) before and after 8 weeks of strength training. Eight
      previously untrained men completed 8 weeks of leg-strength training 3 days week(
      1) on a hack-squat machine; four sets, five repetitions at 85% of one repetition
      maximum each session. Anaerobic capacity was quantified by determining the
      maximal accumulated O(2) deficit during supramaximal cycling. After 8 weeks of
      strength training, one repetition maximum for the hack squat significantly
      increased by 90 +/- 33% when compared to before training. However, 8 weeks of
      strength training did not increase the maximal accumulated O(2) deficit.
      Nevertheless, after 8 weeks of strength training, there was a significant
      increase in time to exhaustion for cycling at 120% VO(2)peak. The increase in
      time to exhaustion after 8 weeks of strength training was accompanied by a
      significant increase in accumulated O(2) uptake. In conclusion, 8 weeks of
      strength training improves supramaximal cycling performance in previously
      untrained subjects. However, increases in time to exhaustion for supramaximal
      cycling following strength training are associated with an increase in the
      contribution of the aerobic energy system rather than an improvement in anaerobic
      capacity.

PMID- 18071743
TI  - The effect of the Ramadan fast on physical performance and dietary habits in
      adolescent soccer players.
AB  - The purpose of this study was to examine the effect of the Ramadan fast on
      performance capacities, dietary habits, and the daily behavioral patterns in
      adolescent (14-16-year-old) soccer players. Nineteen male players performed a
      series of fitness tests before and at the end of Ramadan fast. Caloric intake,
      physical activity pattern and sleep habits were evaluated during the week before
      the Ramadan fast and during the last week of the Ramadan fast. The fast resulted
      in a significant reduction in aerobic capacity [3,000 m run time (mean +/- SD):
      812.8 +/- 73.3 s vs. 819.9 +/- 73.4 s, P < 0.001], speed endurance (Sum 6 x 40 m
      run time: 46.36 +/- 1.36 s vs. 46.73 +/- 1.31 s, P < 0.001, and performance
      decrement: 9.0 +/- 1.5% vs. 9.5 +/- 1.7%, P < 0.05), and jumping performance
      (44.8 +/- 4.5 cm vs. 44.0 +/- 4.5 cm, P < 0.05), but had no significant effect on
      sprint performance (7.38 +/- 0.25 s vs. 7.40 +/- 0.26 s, P = 0.20) or agility (4
      x 10 m shuttle run time: 9.53 +/- 0.35 s vs. 9.55 +/- 0.37 s, P = 0.26). Daily
      intense physical activity was significantly reduced during Ramadan (6.4 +/- 0.2
      h/week vs. 4.5 +/- 0.1 h/week, P < 0.005). There were no significant differences
      in total caloric intake (3,012 +/- 412 kcal/day vs. 3240 +/- 348 kcal/day, P =
      0.39) or total daily sleeping hours (8.6 +/- 0.7 h/day vs. 8.6 +/- 0.5 h/day, P =
      0.80) between Ramadan and a regular month. The results indicate that Ramadan
      fasting can lead to a significant decrease in athletic performance capacities.
      The decrease in performance does not necessarily relate to changes in caloric
      intake and sleeping hours during the fast.

PMID- 18071744
TI  - Effect of moisture transport on microclimate under T-shirts.
AB  - Water transport through garments has influence on the microclimate between the
      garments and the body beneath; thus the thermal comfort feeling for the wearer.
      Soybean protein fiber (SPF), a new type environmental fiber, which has been
      reported to be superior in water transfer, is often blended with cotton to
      improve the water transport property. In this paper, T-shirts made of this
      SPF/cotton blended fabric were focused in comparison with T-shirts made of cotton
      fabric. Wicking and immersion tests were carried out on the two types of fabrics
      to investigate the water transport and absorption properties, respectively; wear
      trials of T-shirts made of the fabrics were also conducted. Comparing with the
      cotton fabric which had better water absorptive property, it was found that the
      blended fabric with superior wicking ability could not only delay the increase of
      the vapor pressure under the T-shirt at the beginning of the exercise, but also
      help to keep it lower through the exercise significantly, and also kept the skin
      temperature under the T-shirt lower. It was made clear that it is the water
      transfer property rather than the water absorption property helps to take away
      sweat quickly and prevents the increase of the humidity and temperature at skin
      surface, thus maintaining a comfort microclimate under garments.

PMID- 18071745
TI  - Identification of elderly fallers by muscle strength measures.
AB  - For efficient prevention of falls among older adults, individuals at a high risk
      of falling need to be identified. In this study, we searched for muscle strength
      measures that best identified those individuals who would fall after a gait
      perturbation and those who recovered their balance. Seventeen healthy older
      adults performed a range of muscle strength tests. We measured maximum and rate
      of development of ankle plantar flexion moment, knee extension moment and whole
      leg push-off force, as well as maximum jump height and hand grip strength.
      Subsequently, their capacity to regain balance after tripping over an obstacle
      was determined experimentally. Seven of the participants were classified as
      fallers based on the tripping outcome. Maximum isometric push-off force in a leg
      press apparatus was the best measure to identify the fallers, as cross-validation
      of a discriminant model with this variable resulted in the best classification
      (86% sensitivity and 90% specificity). Jump height and hand grip strength were
      strongly correlated to leg press force (r = 0.82 and 0.59, respectively) and can
      also be used to identify fallers, although with slightly lower specificity. These
      results indicate that whole leg extension strength is associated with the ability
      to prevent a fall after a gait perturbation and might be used to identify the
      elderly at risk of falling.

PMID- 18071746
TI  - An analysis of the factors contributing to a reduction in the incidence of
      pulmonary complications following an esophagectomy for esophageal cancer.
AB  - BACKGROUND: Pulmonary complications occur most frequently following a
      transthoracic esophagectomy for esophageal cancer and would get to be lethal
      occasionally. In this study, we sought to determine the effect of respiratory
      physiotherapy, corticosteroid administration, and the use of the video-assisted
      thoracoscopic (VATS) esophagectomy with a small thoracotomy incision, on the
      incidence of pulmonary complications following a transthoracic subtotal
      esophagectomy. MATERIALS AND METHODS: Approximately 184 patients who had
      undergone a right transthoracic subtotal esophagectomy for squamous cell
      carcinoma of the thoracic esophagus were studied. To reduce the incidence of
      pulmonary complications, we performed clinical trials using respiratory
      physiotherapy, corticosteroid administration, and the VATS-esophagectomy surgical
      technique. RESULTS: The independent risk factors for pulmonary complications in
      the multivariate logistic regression analysis were not administering
      corticosteroids, blood loss greater than 630 ml, and not providing respiratory
      physiotherapy. In addition, the use of a small surgical incision, less than 10
      cm, for the thoracotomy had no effect on the prevention of pulmonary
      complications. CONCLUSIONS: We concluded that patients with thoracic esophageal
      cancer could undergo a three-field dissection in comparative safety if the
      patients were provided with corticosteroid medication in the perioperative
      period, if the patients received sufficient respiratory physiotherapy, and if
      surgical blood loss was reduced.

PMID- 18071747
TI  - Induction of carbonic anhydrase IX by hypoxia and chemical disruption of oxygen
      sensing in rat fibroblasts and cardiomyocytes.
AB  - CA IX is an active transmembrane carbonic anhydrase isoform functionally
      implicated in cell adhesion and pH control. Human CA IX is strongly induced by
      hypoxia and frequently associated with various tumors. In this study, we
      investigated the expression of the rat CA IX in response to chronic hypoxia and
      to treatment with chemical compounds that disrupt oxygen sensing, including
      dimethyloxalylglycine, dimethylester succinate, diazoxide, and tempol. We brought
      the evidence that expression of CA IX is regulated by hypoxia and hypoxia
      mimicking compounds in immortalized Rat2 fibroblasts and BP6 rat fibrosarcoma
      cells in a cell-type-specific manner. We also demonstrated, for the first time,
      that CA IX is expressed in hypoxic primary rat cardiomyocytes and in immortalized
      H9c2 cardiomyocytes exposed to physiological or chemical hypoxia and that CA IX
      expression is increased in hypoxic rat tissues in vivo. Our findings suggest that
      CA IX expression is not limited to cancer but may be also induced in other
      pathological situations associated with ischemia or metabolic disturbances
      leading to activation of the HIF pathway. These data support the view that rats
      can represent useful model for studies of CA IX as a component of endogenous
      protection mechanisms associated with hypoxia or perturbed oxygen sensing.

PMID- 18071749
TI  - Discovery of Paragonimus proliferus in Northern Vietnam and their molecular
      phylogenetic status among genus Paragonimus.
AB  - During an epidemiological survey for Paragonimus and paragonimosis in northern
      Vietnam, we found extremely large excysted metacercariae (2.50 +/- 0.14 mm in
      length and 0.72 +/- 0.08 mm in width; mean +/- standard deviation of 20 samples)
      in mountainous crabs, Potamiscus mieni. Adult worms were successfully obtained by
      intraperitoneal injection with those large excysted metacercariae in a cat.
      Morphological and morphometric data of those large excysted metacercariae and the
      adult worms derived from them are identical to those of Paragonimus proliferus
      found in Yunnan province, China. However, when second internal transcribed spacer
      region and cytochrome oxidase subunit 1 gene sequences of those metacercariae and
      adult worms were compared with those of known Paragonimus spp. deposited in the
      GenBank, they were almost completely identical to those of Paragonimus hokuoensis
      metacercariae in China, of which adult worms have never been reported. This is
      the first record of P. proliferus in Vietnam and the first record from outside of
      China. Phylogenetic relationship between P. proliferus and P. hokuoensis is
      discussed.

PMID- 18071748
TI  - Dynamic modulation of intracellular glucose imaged in single cells using a FRET
      based glucose nanosensor.
AB  - To study intracellular glucose homeostasis, the glucose nanosensor FLIPglu-600
      microM, which undergoes changes in fluorescence resonance energy transfer (FRET)
      upon interaction with glucose, was expressed in four mammalian cell lines: COS-7,
      CHO, HEK293, and C2C12. Upon addition of extracellular glucose, the intracellular
      FRET ratio decreased rapidly as intracellular glucose increased. The kinetics
      were fast (tau=5 to 15 s) in COS and C2C12 cells and slow (tau=20 to 40 s) in HEK
      and CHO cells. Upon removal of extracellular glucose, the FRET ratio returned to
      its initial value at similar rates (tau=15 to 40 s) in all cell types. In all
      cell types, the glucose uptake FRET signal was blocked by the glucose transporter
      (GLUTx) inhibitor cytochalasin B and was not affected by the Na/glucose
      transporter inhibitor phlorizin. Glucose clearance was inhibited by the
      glycolytic inhibitor iodoacetate. Using beta-escin to permeabilize the cell, we
      found that the glucose gradient across the membrane was strongly dependent on the
      rates of glucose uptake versus glucose clearance. With 10 mM extracellular
      glucose and a high rate of glucose clearance, intracellular glucose level fell
      below 100 muM when glucose uptake rate was low, whereas it exceeded 0.5 mM when
      glucose uptake was high. Cells cultured in high glucose maintained lower basal
      intracellular glucose levels than cells cultured in low glucose, attributed to
      "reciprocal regulation" of glycolysis and gluconeogenesis. Basal glucose level
      also increased with elevated temperatures. Experiments performed with C2C12 cells
      demonstrated a shift from fast glucose uptake to slow glucose uptake in the
      absence of insulin during differentiation.

PMID- 18071750
TI  - Use of triclabendazole for treatment of patients co-infected by Fasciola spp. and
      S. mansoni in Behera Governorate, Egypt.
AB  - Praziquantel is still very effective for the treatment of schistosomiasis, but
      there are rising concerns on the potential risk of developing resistances because
      of the extensive use of this drug. Triclabendazole, a systemic anthelmintic, is
      very effective against other trematodes such as Paragonimus spp. and Fasciola
      spp. It has been reported to be effective in vitro and in experimental animals
      against Schistosoma mansoni. However, its antischistosomal efficacy in humans has
      not yet been evaluated. The objective of the study was to evaluate the efficacy
      of triclabendazole at the dosage currently used for the treatment of human
      fascioliasis (10mg/kg body weight) in subjects co-infected with S. mansoni and
      Fasciola spp. The study was carried out in Behera, a highly endemic area for both
      parasites, by personnel of the Egyptian Ministry of Health and Population. Ten
      subjects (m = 4, f = 6; age, 8-58years), who were infected at the same time by
      Fasciola spp. and S. mansoni, were enrolled. Six weeks after therapy, seven
      subjects were still excreting ova of S. mansoni, whereas none was excreting
      Fasciola spp. ova. At the given dosage, triclabendazole appeared not to be
      sufficiently effective in the treatment of S. mansoni.

PMID- 18071751
TI  - A syndromic form of autosomal recessive congenital microcephaly (Jawad syndrome)
      maps to chromosome 18p11.22-q11.2.
AB  - We report a consanguineous Pakistani family with seven affected individuals
      showing a syndromic form of congenital microcephaly. Clinical features of
      affected individuals include congenital microcephaly with sharply slopping
      forehead, moderate to severe mental retardation, anonychia congenita, and digital
      malformations. By screening human genome with microsatellite markers, this
      autosomal recessive condition was mapped to a 25.2 cM interval between markers
      D18S1150 and D18S1100 on chromosome 18p11.22-q12.3. However, the region of
      continuous homozygosity between markers D18S1150 and D18S997 spanning 15.33 cM,
      probably define the most likely candidate region for this condition. This region
      encompasses a physical distance of 12.03 Mb. The highest two-point LOD score of
      3.03 was obtained with a marker D18S1104 and multipoint score reached a maximum
      of 3.43 with several markers. Six candidate genes, CEP76, ESCO1, SEH1L, TUBB6,
      ZNF519, and PTPN2 were sequenced, and were found to be negative for functional
      sequence variants.

PMID- 18071752
TI  - Cellular localization of a putative Na(+)/H (+) exchanger 3 during ontogeny in
      the pronephros and mesonephros of the Japanese black salamander (Hynobius
      nigrescens Stejneger).
AB  - The cloning of cDNA and an examination of the tissue distribution of Na(+)/H(+)
      exchanger 3 (NHE3) were carried out in the Japanese black salamander, Hynobius
      nigrescens. The cellular localization of Hynobius NHE3 was examined by in situ
      hybridization and immunohistochemistry during ontogeny in the nephron of the
      pronephros and mesonephros of the salamander. The partial amino acid sequence of
      Hynobius NHE3 was 81% and 72% identical to rat NHE3 and stingray NHE3,
      respectively. Hynobius NHE3 mRNA and protein were exclusively expressed along the
      late portion of the distal tubule to the anterior part of the pronephric duct of
      premetamorphic larvae (IY stages 43-50). NHE3 mRNA was expressed in the
      pronephros but not in the external gills in the larvae at the digit
      differentiation stage (IY stage 50). In the adult, mRNA was strongly expressed in
      the mesonephros but not in the ventral and dorsal skin. In juvenile and adult
      specimens, NHE3 immunoreactivity was observed at the apical membrane of the
      initial parts of the distal tubules of the mesonephric kidney.
      Immunohistochemical and in situ hybridization studies suggested that Na(+)
      absorption coupled with H(+) secretion via NHE3 occurred in the distal nephron of
      the pronephros and mesonephros. This is the first study to indicate NHE3
      expression during ontogeny in amphibians.

PMID- 18071753
TI  - GDNF prevents TGF-beta-induced damage of the plasma membrane in cerebellar
      granule neurons by suppressing activation of p38-MAPK via the
      phosphatidylinositol 3-kinase pathway.
AB  - Transforming growth factor-beta (TGF-beta) and glial-cell-line-derived
      neurotrophic factor (GDNF) have been shown to synergize in several paradigms of
      neuronal survival. We have previously shown that cerebellar granule neurons (CGN)
      degenerate in low potassium via ERK1/2 (extra-cellular-regulated kinase)
      dependent plasma membrane (PM) damage and caspase-3-dependent DNA fragmentation.
      Here, we have investigated the putative synergistic function of GDNF and TGF-beta
      in CGN degeneration. GDNF alone prevents low-potassium-induced caspase-3
      activation and DNA fragmentation but does not affect either low-potassium-induced
      ERK activation or PM damage. TGF-beta alone does not affect low-potassium-induced
      DNA fragmentation but potentiates low-potassium-induced PM damage. This effect of
      TGF-beta is independent of ERK1/2 activation but dependent on p38-MAPK (mitogen
      activated protein kinase) activation. When co-applied with TGF-beta, GDNF
      paradoxically antagonizes TGF-beta-induced potentiation of PM damage by
      inhibiting TGF-beta-induced p38-MAPK activation. In addition, PI3K
      (phosphatidylinositol 3-kinase) inhibitors abolish the GDNF effect. This study
      thus demonstrates a differential mechanism of action of GDNF and TGF-beta on CGN
      degeneration. GDNF inhibits caspase-3-dependent DNA fragmentation but does not
      affect ERK-dependent PM damage. However, GDNF can attenuate TGF-beta-induced p38
      MAPK-dependent PM damage via the PI3K pathway.

PMID- 18071754
TI  - Immunofluorescence analysis of the internal brain anatomy of Nereis diversicolor
      (Polychaeta, Annelida).
AB  - Comparative analyses of neuroanatomical characters can make valuable
      contributions to the inference of phylogenetic relationships. Whereas
      investigations in this field are numerous for arthropods, in-depth studies on
      other protostomes are sparse. Here, we provide a survey of the internal
      neuroarchitecture of the brain of the aciculate ragworm Nereis diversicolor
      (Polychaeta, Annelida). Descriptions are based on confocal laser scanning
      microscope analyses of brain sections labeled with the nuclear marker DAPI and
      antibodies raised against FMRF-amide, serotonin, and histamine. Autofluorescence
      of the nervous tissue has been utilized to further elucidate the anatomical
      structures of the brain. The architecture of two major brain compartments, i.e.,
      the paired mushroom bodies and the central optic neuropil, is described in
      detail. The findings are compared with existent literature on polychaete
      neuroanatomy and on arthropod neuroanatomy, and possible phylogenetic
      implications are outlined.

PMID- 18071755
TI  - Real-time polymerase chain reaction, in situ hybridization and
      immunohistochemical localization of insulin-like growth factor-I and myostatin
      during development of Dicentrarchus labrax (Pisces: Osteichthyes).
AB  - The distribution of insulin-like growth factor-I (IGF-I) and myostatin (MSTN) was
      investigated in sea bass (Dicentrarchus labrax) by real-time polymerase chain
      reaction (PCR), in situ hybridization (ISH) and immunohistochemistry. Real-time
      PCR indicated that IGF-I mRNA increased from the second day post-hatching and
      that this trend became significant from day 4. ISH confirmed a strong IGF-I mRNA
      expression from the first week post-hatching, with the most abundant expression
      being detected in the liver of larvae and adults. Real-time PCR also showed that
      the level of MSTN mRNA increased significantly from day 25. The expression of
      MSTN mRNA was higher in muscle and almost absent in other anatomical regions in
      both larvae and adults. Interestingly, the lateral muscle showed a quantitative
      differential expression of IGF-I and MSTN mRNAs in red and white muscle,
      depending on the developmental stage examined. IGF-I immunoreactivity was
      detected in developing intestine at hatching and in skeletal muscle, skin and
      yolk sac. MSTN immunostaining was evident in several tissues and organs in both
      larvae and adults. Both IGF-I and MSTN proteins were detected in the liver from
      day 4 post-hatching and, subsequently, in the kidney and heart muscle from day
      10. Our results suggest, on the basis of a combined methodological approach, that
      IGF-I and MSTN are involved in the regulation of somatic growth in the sea bass.

PMID- 18071756
TI  - Characterization of obestatin- and ghrelin-producing cells in the
      gastrointestinal tract and pancreas of rats: an immunohistochemical and electron
      microscopic study.
AB  - Both ghrelin and obestatin are derived from preproghrelin by post-translational
      processing. We have morphologically characterized the cells that produce
      obestatin and ghrelin in new-born and adult Sprague-Dawley rats that were freely
      fed, fasted, or subjected to gastric bypass surgery or reserpine treatment.
      Tissue samples collected from the gastrointestinal tract and pancreas were
      examined by double-immunofluorescence staining, immunoelectron microscopy, and
      conventional electron microscopy. Obestatin was present in the stomach, duodenum,
      jejunum, colon, and pancreas. In the stomach, differences were noted in the
      development of obestatin- and preproghrelin-immunreactive (IR) cells on the one
      hand and ghrelin-IR cells on the other, particularly 2 weeks after birth.
      Preproghrelin- and obestatin-IR cells were more numerous than ghrelin-IR cells in
      the stomach, suggesting the lack of ghrelin in some A-like cells. Most obestatin
      producing cells in the stomach were distributed in the basal part of the oxyntic
      mucosa; these cells co-localized with chromogranin A (pancreastatin) and vesicle
      monoamine transporters type 1 and 2, but not with serotonin or histidine
      decarboxylase. Immunoelectron microscopy revealed the obestatin- and ghrelin
      producing cells to be A-like cells, characterized by numerous highly electron
      dense granules containing ghrelin and obestatin. Some granules exhibited an even
      electron density with thin electron-lucent halos, suggestive of monoamines.
      Feeding status, gastric bypass surgery, and reserpine treatment had no obvious
      effect on the A-like cells. In the pancreas, obestatin was present in the
      peripheral part of the islets, with a distribution distinct from that of glucagon
      producing A cells, insulin-producing beta cells, and cells producing pancreatic
      polypeptide Y. Thus, obestatin and ghrelin co-localize with an anticipated
      monoamine in A-like cells in the stomach, and obestatin is found in pancreatic
      islets.

PMID- 18071757
TI  - Plasma metabolites and migration physiology of semipalmated sandpipers: refueling
      performance at five latitudes.
AB  - Long-distance bird migration is fueled by energy gathered at stopover sites along
      the migration route. The refueling rate at stopover sites is a determinant of
      time spent at stopovers and impacts the overall speed of migration. Refueling
      rate during spring migration may influence the fitness of individuals via changes
      in the probability of successful migration and reproduction during the subsequent
      breeding season. We evaluated four plasma lipid metabolites (triglycerides,
      phospholipids, beta-OH-butyrate, and glycerol) as measures of refueling rate in
      free-living semipalmated sandpipers (Calidris pusilla) captured at non-breeding
      areas. We described the spatial and temporal variation in metabolite
      concentrations among one winter site in the Dominican Republic and four stopover
      sites in the South Atlantic and Mid-Atlantic Coastal Plain regions of North
      America. Triglycerides and beta-OH-butyrate clearly identified spatial variation
      in refueling rate and stopover habitat quality. Metabolite profiles indicated
      that birds had higher refueling rates at one site in the Mid-Atlantic Coastal
      Plain than at three sites on the South Atlantic Coastal Plain and one site in the
      Dominican Republic. Temporal variation in lipid metabolites during the migration
      season suggested that male semipalmated sandpipers gained more weight at
      stopovers on the South Atlantic Coastal Plain than did females, evidence of
      differential migration strategies for the sexes. Plasma lipid metabolites provide
      information on migration physiology that may help determine stopover habitat
      quality and reveal how migratory populations use stopover sites to refuel and
      successfully complete long-distance migrations.

PMID- 18071758
TI  - Optimization of extracellular thermotolerant alkaline protease produced by marine
      Roseobacter sp. (MMD040).
AB  - Marine endosymbiontic Roseobacter sp. (MMD040), which produced high yields of
      protease, was isolated from marine sponge Fasciospongia cavernosa, collected from
      the peninsular coast of India. Maximum production of enzyme was obtained in Luria
      Bertani broth. Catabolite repression was observed when the medium was
      supplemented with readily available carbon sources. The optimum temperature and
      pH for the enzyme production was 37 degrees C and 7.0, respectively. The enzyme
      exhibited maximum activity in pH range of 6-9 with an optimum pH of 8.0 and
      retained nearly 92.5% activity at pH 9.0. The enzyme was stable at 40 degrees C
      and showed 89% activity at 50 degrees C. Based on the present findings, the
      enzyme was characterized as thermotolerant alkaline protease, which can be
      developed for industrial applications.

PMID- 18071759
TI  - Complications of pediatric live-donor kidney transplantation: a single center's
      experience in Egypt.
AB  - Our objective was to study the complications of chronic renal failure (CRF) among
      pediatric live-donor kidney transplant recipients. Between March 1976 and
      December 2005, 1,785 live-donor kidney transplantations were carried out at our
      center. Of the recipients, 292 were 20 years old or younger (mean age 12.8 years,
      ranging from 4 years to 20 years). Clinical and laboratory parameters of these
      292 patients were analyzed retrospectively. They were 182 boys and 110 girls.
      Patients who had received transplants before 1988 were treated with prednisolone
      and azathioprine as combined therapy. From 1988 to 1998, a triple regimen
      comprising prednisolone, azathioprine and cyclosporine A (CsA) was administered.
      Tacrolimus and mycophenolate mofetil (MMF) were introduced as primary therapy in
      1998. Growth, anemia, infections, and surgical, cardiac, neurologic, bone and
      other medical complications were assessed. Triple-drug immunosuppression
      (prednisone + CsA + azathioprine) was used in 68.2% of transplants. Acute
      rejection rate was 47.6%; chronic rejection rate was 31%. Hypertension (62%) was
      the commonest complication. Anemia was diagnosed in 61%. A substantial proportion
      of patients (48%) were short, with height standard deviation scores (SDSs) of
      less than -1.88. The overall infection rate was high, and the majority (54%) was
      bacterial. Malignancy was diagnosed in eight (3%) patients. The incidence of
      urological complications was 14%, and that of vascular complications was 1%.
      Cardiac complications included left ventricular hypertrophy (LVH) in 47.9% of
      patients, left atrial enlargement (31.5%) and left ventricular dilatation and
      systolic dysfunction (13.7% for each). Neuropathic changes were found in 19% of
      our cases, with the distal muscles of lower limbs more affected. Other
      complications included avascular bone necrosis in 8% (all of them in the hip
      joint) and bone loss in 60% of patients. We concluded that, despite the long-term
      success of pediatric renal transplantation in a developing country, there is a
      risk of significant morbidity.

PMID- 18071760
TI  - Clinical spectrum and outcome of crescentic glomerulonephritis in children in
      developing countries.
AB  - Crescentic glomerulonephritis (CsGN) is an uncommon entity in children. This
      prospective study was conducted to evaluate the aetiology, clinical spectrum and
      outcome in children with crescentic glomerulonephritis. The single-centre
      prospective study comprised of 22 children with biopsy proven CsGN who had been
      referred to our institute over the period January 2000 to December 2005. These
      patients were subjected to detailed clinical and biochemical examinations. The
      diagnosis of underlying renal disease was based on various criteria, including
      the clinical picture, serology and histopathology. The patients received
      intravenous methyl prednisolone, oral steroid treatment, and oral
      cyclophosphamide with or without plasmapheresis. All patients received supportive
      care, including control of hypertension and oedema and supportive management of
      renal insufficiency. During this 5-year period, CsGN accounted for 5.1% of all
      biopsies done in children. The mean age was 12.27 years (range 4 years to 18
      years). There were eight girls and 14 boys. The mean duration of symptoms prior
      to referral was 2.47 months (range 5 days to 21 months). Aetiology was immune
      complex in 19 cases, anti-glomerular basement membrane (anti-GBM) antibody
      disease in two cases and pauci-immune (Wegener's granulomatosis) in one case. The
      percentage of crescents ranged from 50% to 100% (mean 70.6%). Twenty-one out of
      22 (95.5%) children in our series had hypertension at presentation that required
      treatment with antihypertensive medications. The serum creatinine level at
      presentation ranged from 1.5 mg/dl to 11.4 mg/dl (mean 5.5 mg/dl). Of the 22
      children, two were lost to follow-up, while the mean follow-up period of the rest
      of the 20 children was 8.13 months (range 1 month to 43 months). At the last
      follow-up of the 22 children, ten had stage 5 chronic kidney disease (CKD) and
      three had stage 4 CKD, while seven children had a calculated glomerular
      filtration rate (GFR) of >60 ml/min per 1.73 m(2) body surface area. Persistent
      proteinuria was seen on follow-up in the majority [13/20 (65%)] of patients. The
      outcome of CsGN in children continues to be poor, in our experience, due to
      delayed referral and delayed diagnosis. This was correlated histologically by the
      presence of fibrocellular crescents in the majority of our patient. Thus CsGN
      should be treated as a renal emergency. A greater awareness of this disease needs
      to be created amongst the referring paediatricians in developing countries to
      facilitate early diagnosis and prompt treatment.

PMID- 18071762
TI  - Service user experiences of information delivery after a diagnosis of cancer: a
      qualitative study.
AB  - GOALS OF WORK: This paper presents findings from a qualitative study
      investigating service users' experiences of a patient information pathway after a
      diagnosis of cancer. MATERIALS AND METHODS: Patients (27) and relatives (20) were
      recruited from two identified Cancer Network sites representing a pathway that
      had been information mapped (Lung) and one which had not (Head and Neck).
      Respondents participated in up to three qualitative interviews in the year after
      diagnosis. MAIN RESULTS: The need for information in response to serious health
      problems has become widely accepted. Providing cancer patients and their carers
      with high-quality information throughout their care pathway is a policy priority.
      However, the study findings contribute to a growing body of evidence that far
      from embracing the active role of "expert patient", many patients continue to
      prefer verbal to written information, to trust in health professionals as their
      primary and preferred source of information, and to be quite cautious and
      selective about what they want to know about their illness. CONCLUSIONS: Good
      information is regarded as a prerequisite for informed decision making and a
      primary means of coping with the stress of illness. However, patient attitudes to
      information are complex and encompass resistance, ambivalence and indifference,
      active engagement and interest. The study findings reinforce the need for health
      professionals to develop competence as skilled communicators, and for efficient
      local systems of information transfer between service agencies and health
      professionals as prerequisites for delivery of the timely, tailored and
      personalized information which patients require.

PMID- 18071761
TI  - Biomarkers for cancer cachexia: is there also a genetic component to cachexia?
AB  - INTRODUCTION: Cancer cachexia is a severe debilitating disorder, which causes
      significant morbidity and mortality. In clinical practice, cachexia is often not
      treated until a late stage, when therapeutic options are limited. OBJECTIVE: It
      is therefore of great interest to analyse early biomarkers of this syndrome.
      CONCLUSION: In this review article, we summarise recent biomarkers found in
      various body compartments. We also explore the likelihood of a genetic
      predisposition to cachexia and focus on the potential role of single nucleotide
      polymorphisms in genes coding for pro- and anti-inflammatory cytokines, and
      'atrogenes' associated with wasting in skeletal muscle.

PMID- 18071763
TI  - Palliative sedation in Latin America: survey on practices and attitudes.
AB  - INTRODUCTION: Palliative sedation (PS) is the subject of ethical and legal
      debates worldwide. Statistics of its utilization are available in developed
      countries; however, in Latin America, these data are scarcely known. The purpose
      of this research was to determine the practices and attitudes of palliativists in
      Latin America towards PS. MATERIALS AND METHODS: Data was collected during the
      Latin American Congress on Palliative Care in Isla Margarita, Venezuela. A total
      of 89 professionals participated in this survey. RESULTS: It was found that the
      use of PS was positively associated with being a physician and being members of a
      palliative care (PC) group. On the other hand, it was found that being a
      psychologist and identifying barriers toward PS limited its utilization.
      DISCUSSION: The findings of this study support the need to establish clinical
      guidelines for its utilization and to educate other specialists on end-of-life
      care approaches, and the need to develop PC programs in acute care hospitals in
      Latin America.

PMID- 18071764
TI  - Is cancer-related fatigue more strongly correlated to haematological or to
      psychological factors in cancer patients?
AB  - GOALS OF WORK: Cancer-related fatigue is a very frequent problem in cancer,
      interfering with many patients' life activities. Anaemia is present in a large
      number of fatigued patients. The aim of this study was to evaluate cancer-related
      fatigue, in relation with haematic haemoglobin levels and the presence of anxiety
      and depression. MATERIALS AND METHODS: The Functional Assessment Of Chronic
      Illness Therapy-Fatigue scale was used to assess fatigue. The Hospital Anxiety
      and Depression Scale was administered to screen for psychological distress.
      Haematological values were measured by blood tests. All data were analysed using
      Chi-squared, and a logistic regression analysis was conducted. MAIN RESULTS:
      Eighty patients were enrolled in the study. Significant associations were found
      between fatigue and depression, fatigue and anxiety and between fatigue and
      haemoglobin. CONCLUSION: Anxiety and depression, other than heamoglobin levels,
      were found associated with fatigue. Hence, implications for a multi-dimensional
      treatment of fatigue are discussed.

PMID- 18071765
TI  - Occult hepatitis B virus infection in Lebanese patients with chronic hepatitis C
      liver disease.
AB  - Occult hepatitis B virus (HBV) infection, characterised by the presence of HBV
      infection with undetectable hepatitis B surface antigen (HBsAg), was investigated
      in 98 Lebanese patients with chronic hepatitis C liver disease and 85 control
      subjects recruited from eight institutions in different parts of the country. The
      prevalence of occult HBV infection ranged from 11.9% to 44.4% in hepatitis C
      virus (HCV)-infected patients and it increased with increasing severity of the
      liver disease. The overall rate of HBV DNA in our 98 HCV-infected patients was
      16.3%. On the other hand, the rate of HBV DNA was 41.0% in anti-HBc alone
      positive patients compared to only 7.1% in healthy controls who were also anti
      HBc alone positive (p < 0.001). Moreover, the prevalence HBV DNA increased with
      increasing severity of the liver disease, but this increase was only marginally
      significant and, perhaps, could have been significant if more patients were
      involved in the study. Although Lebanon is an area of low endemicity for both HBV
      and HCV, occult HBV infection is common in HCV-infected patients. The presence of
      HBV DNA, therefore, presents a challenge for the effective laboratory diagnosis
      of hepatitis B, particularly if polymerase chain reaction (PCR)-based HBV
      detection methods are not used.

PMID- 18071766
TI  - Relationship between pathogenicity for humans and stx genotype in Shiga toxin
      producing Escherichia coli serotype O157.
AB  - To examine the reason why people infected with Shiga toxin (Stx) producing
      Escherichia coli (STEC) O157 strains develop varying clinical manifestations, 65
      STEC O157 isolates originating from 64 different occurrences of infection in
      Miyazaki Prefecture in 2001-2003 and their 79 infected individuals were analyzed
      by stx genotyping, quantitative analysis of reversed passive latex agglutination
      (RPLA), genomic DNA analysis using pulsed-field gel electrophoresis (PFGE), and
      clinical manifestations. The isolates were found to carry the following stx
      genes: stx2vha alone (60.0%), stx1/stx2 (27.7%), stx1/stx2vha (6.1%), stx2 alone
      (3.1%), and stx2/stx2vha (3.1%). No strain carried the stx1 gene alone. STEC
      strains carrying stx2 were more frequently associated with clinical
      manifestations of hemolytic-uremic syndrome (HUS) or bloody diarrhea than those
      carrying stx2vha. Clusters of PFGE banding patterns were correlated well with the
      stx genotypes. We conclude that stx genotype is one of the important factors of
      clinical outcome of STEC O157 infection and that pathogenicity for humans was
      higher in the stx2 genotype strains than in the stx2vha genotype strains, as
      reported previously by other researchers. Further, we newly found that four
      clusters identified by PFGE using restriction enzyme XbaI, stx genotypes and
      clinical manifestations were well correlated with each other.

PMID- 18071767
TI  - Invasive gastric mucormycosis: CT findings.
AB  - Mucormycosis is an uncommon fungal infection primarily seen in immunocompromised
      patients. We present a patient whose hospital course was rapidly complicated by
      invasive mucormycosis, which caused his death. Computed tomography (CT) was very
      helpful in characterizing the extent of involvement and directing clinical
      management.

PMID- 18071768
TI  - MDCT arteriographic spectrum in acute blunt peripheral trauma--a pictorial
      review.
AB  - Unrecognized arterial injuries in patients with blunt peripheral trauma can cause
      significant morbidity. Rapid diagnosis and localization of arterial injury is
      required for choosing the optimal surgical strategy in patients with extremity
      trauma. Multidetector computed tomography (MDCT) arteriography provides an
      accurate, rapid, and noninvasive means for diagnosis of arterial injuries. We
      discuss and depict the spectrum of findings on MDCT arteriography in acute blunt
      peripheral trauma.

PMID- 18071769
TI  - Great saphenous vein thrombosis causing acute pulmonary embolism suggested by
      combined CT venography and pulmonary angiography.
AB  - Pulmonary embolism is a life-threatening condition, which is most commonly
      related to deep vein thrombosis. Varicose vein thrombosis, a very common disease,
      is seldom reported as being related to pulmonary embolism. We present combined
      computed tomography venography and pulmonary angiography findings suggesting that
      thrombosed varicosities of a great saphenous vein caused acute pulmonary embolism
      in a 30-year-old male.

PMID- 18071770
TI  - Periodic limb movement during sleep and chronic obstructive pulmonary disease.
AB  - The aim of this work was to study whether chronic obstructive pulmonary disease
      (COPD) subjects exhibited periodic limb movement (PLMs) during sleep. A
      retrospective case control study was conducted in the referral sleep disorders
      laboratory in the University of Patras in southwest Greece. A sample of 23 COPD
      subjects was compared with 14 severe obstructive sleep apnea (OSA) subjects and
      18 periodic limb movement disorder (PLMD) subjects. The PLM Index (PLMI) and PLMs
      Arousal Index (PLMAI) in COPD subjects differ (p<0.05) from severe OSA patients.
      The PLMAI differ (p < 0.05) between COPD and PLMD subjects. Spearman's
      correlation showed a positive statistical significant correlation between PLMI
      and PLMAI in the entire population and in COPD subjects. There was no statistical
      significant correlation between sleep-related symptoms and the occurrence of PLMs
      disorder in COPD patients. In our study, PLMs with associated arousals are often
      seen in COPD subjects. Further prospective studies will be necessary to clarify
      the mechanisms whereby the reduction in PLMs in COPD patients improved their
      sleep and quality of life.

PMID- 18071771
TI  - A novel method for automated classification of epileptiform activity in the human
      electroencephalogram-based on independent component analysis.
AB  - Diagnosis of several neurological disorders is based on the detection of typical
      pathological patterns in the electroencephalogram (EEG). This is a time-consuming
      task requiring significant training and experience. Automatic detection of these
      EEG patterns would greatly assist in quantitative analysis and interpretation. We
      present a method, which allows automatic detection of epileptiform events and
      discrimination of them from eye blinks, and is based on features derived using a
      novel application of independent component analysis. The algorithm was trained
      and cross validated using seven EEGs with epileptiform activity. For epileptiform
      events with compensation for eyeblinks, the sensitivity was 65 +/- 22% at a
      specificity of 86 +/- 7% (mean +/- SD). With feature extraction by PCA or
      classification of raw data, specificity reduced to 76 and 74%, respectively, for
      the same sensitivity. On exactly the same data, the commercially available
      software Reveal had a maximum sensitivity of 30% and concurrent specificity of
      77%. Our algorithm performed well at detecting epileptiform events in this
      preliminary test and offers a flexible tool that is intended to be generalized to
      the simultaneous classification of many waveforms in the EEG.

PMID- 18071772
TI  - [Use of buccal mucosa in urethral surgery].
AB  - Buccal mucosa grafts have proven reliable in urethral surgery. For augmentation
      urethroplasty, the graft can be used as a ventral or dorsal onlay. If the graft
      was used as an onlay, the results were much better than in substitution
      urethroplasty with the graft used as a tube. In patients with complex strictures
      or severe cases of hypospadias or epispadias, a two-stage technique using a
      buccal mucosa inlay graft can be applied. After 6 months, the well-revascularized
      buccal mucosa strip can be tubularized and covered with a tunica dartos or tunica
      vaginalis flap. In the future, for correction of larger defects, buccal mucosa
      cells can be cultured in vitro on biodegradable matrices. These larger buccal
      mucosa transplants could minimize the morbidity at the donor site. Future studies
      must clarify if the new technology of nanofibers can be of advantage by producing
      better matrices.

PMID- 18071773
TI  - [The psychosocial/-sexual development of boys with hypospadias].
AB  - Boys with hypospadias can suffer from specific psychological stress as a result
      of genital surgery and a cosmetically and/or functionally impaired penis. During
      recent decades intensive efforts have been made to improve the surgical
      techniques; yet the psychosocial and psychosexual development of children and
      adolescents after hypospadias surgery has only rarely been investigated. While
      the results of the few studies are altogether very contradictory, they also
      indicate that hypospadias patients suffer from specific problems like a negative
      perception of genital appearance. Therefore, they should be offered long-term
      follow-ups and psychosocial support until they reach young adulthood. For future
      research, it is necessary to systematically investigate the boys' quality of life
      and development in methodologically sound studies.

PMID- 18071775
TI  - [Bulletin of the German Society for Urology].

PMID- 18071774
TI  - [Ureterocystoplasty in the treatment of "low-compliance" bladder in children].
AB  - In cases of inadequate or insufficient conservative treatment of non-compliant
      bladders the function of the upper urinary tract is jeopardized. We present our
      experience with ureterocystoplasty as one possible treatment option.A total of
      eight children underwent ureterocystoplasty. The etiology of bladder non
      compliance and the need for augmentation was neurogenic in five children,
      posterior urethral valves in two children, and in one child after repeated
      antireflux surgery. In all patients the kidney of the used ureter was
      functionless. Surgery was done through a transperitoneal approach. Following
      nephrectomy, the renal pelvis and the ureter were spatulated and sutured into the
      bladder incision. An additional MACE procedure was performed in three patients,
      antireflux surgery for the contralateral kidney in two patients, and one patient
      underwent stone removal in the remaining kidney. In one patient the ureter was
      used as a free transplant and was covered by an omental flap. In addition a
      simultaneous living donor kidney transplant was performed. The storage function
      could be improved in all patients. The function of the ureter which was used as a
      free transplant showed good clinical results. The longest follow-up is 8 years.
      Ureterocystoplasty is a useful and metabolically neutral alternative to bowel
      segments. In patients with only one functioning kidney and a contralateral
      megaureter, ureterocystoplasty is the treatment of choice in our institution.

PMID- 18071779
TI  - High sensitivity C-reactive protein and endothelial function in Chilean patients
      with history of Kawasaki disease.
AB  - Kawasaki disease (KD) produces endothelial inflammation, which may lead to
      dilatation and aneurysms of coronary and peripheral arteries. Previous studies
      have suggested that these patients can present endothelial dysfunction that can
      predispose to coronary vascular events late after KD. The purpose of this study
      was to determine the cardiovascular risk profile and endothelial function of
      Chilean children with history of KD. In a prospective case-control study, 11
      patients with history of KD (age 10.6 +/- 2.0 years, interval from initial
      episode 8.1 +/- 3.6 years) and 11 healthy, age-, gender-, and BMI z score-matched
      controls were evaluated with blood pressure (BP), a fasting lipid profile, high
      sensitivity C-reactive protein (hsCRP), and flow-mediated dilatation of the
      brachial artery (FMD). One KD patient (9.1%) had persistent coronary aneurysms.
      There was a significant difference of mean and log-transformed concentrations of
      hsCRP between case and control groups (2.3 +/- 3.0 vs 0.5 +/- 0.3 mg/l, P =
      0.045). None of the patients with elevated hsCRP had persistent coronary arterial
      lesions. No difference was found in systolic BP z score between the case and
      control groups. Diastolic BP z score was significantly higher in cases than
      controls (P = 0.039). There were no significant differences of FMD between cases
      and controls. Mean fasting total cholesterol, high-density and low-density
      lipoprotein, and triglycerides in cases were normal, with no significant
      difference vs controls. This study shows that Chilean children with history of KD
      have increased levels of hsCRP, possibly reflecting persistent low-grade
      inflammation. The prognostic value of hsCRP in KD patients deserves further
      investigation.

PMID- 18071780
TI  - Hearing difficulties are common in patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is well known to affect many different organ systems.
      Previous work suggests that this includes the auditory system and that measures
      of hearing may be related to indices of RA disease activity. The aims of this
      study were to determine whether hearing loss in young subjects with rheumatoid
      arthritis is greater than would be expected in the normal population and whether
      disease activity or duration correlate with hearing levels. About 55 patients
      (less than 50 years old) with RA were sampled from a secondary-care-level
      population. Pure-tone audiograms, transient evoked otoacoustic emissions (TEOAEs)
      and rheumatological assessment including disease duration and the DAS28 disease
      activity score were carried out. Subjective hearing loss was a common symptom
      with a prevalence of 29.6% (95% CI 17.8-42.2%). The prevalence of conductive
      hearing loss was 1.9% (95% CI 0.3-9.7%)). Subjects with RA had worse hearing than
      expected at low and middle frequencies (250 Hz to 2 kHz). TEOAEs were absent in
      15 of 84 (18%, 95% CI 11-27%) normal ears. No relationship was demonstrated
      between hearing thresholds and markers of disease activity or other
      rheumatological parameters. Hearing loss is common in young people with RA and
      should be sought by clinicians caring for this patient population. TEOAEs are
      absent in a higher proportion of patients than expected, and this may be a marker
      of early asymptomatic hearing loss. It may be conductive or sensorineural and may
      take any configuration, including low-frequency loss.

PMID- 18071781
TI  - Prevalence and patterns of back pain and residual limb pain in lower limb
      amputees at the National Rehabilitation Hospital.
AB  - AIMS: To examine the prevalence and impact of back pain (BP) and residual limb
      pain (RLP) in ambulatory lower limb amputees (LLAs). METHODS: Patients completed
      questionnaires regarding demographics, their amputation, occurrence of BP and
      RLP. Visual analogue scales assessed pain severity and effect on activities of
      daily living (ADLs), recreational, family and social life (RFS), and ability to
      work. Descriptive statistics were compiled and relationships between pain and
      details of amputation were examined. RESULTS: A total of 107 patients (88 males,
      19 females) participated; mean age 51.1 years. Fifty-one patients (47.7%)
      suffered BP, mean intensity 5.3, mean interference with ADLs, RFS, ability to
      work 3.5, 3.8, 3.4, respectively. Sixty (56.1%) suffer from RLP, mean intensity
      5.7; mean interference with ADLs, RFS, ability to work 2.9, 2.8, 3.9,
      respectively. BP intensity increased with age; RLP intensity was greatest among
      vasculopaths. CONCLUSIONS: Irish LLAs maintain functional capacity despite
      suffering moderate intensity BP and RLP.

PMID- 18071782
TI  - Cadmium and zinc in Mar Chiquita coastal lagoon (Argentina): salinity effects on
      lethal toxicity in juveniles of the burrowing crab Chasmagnathus granulatus.
AB  - The large Argentine marine littoral zone is characterized by great number of
      wetlands and includes only one coastal lagoon, Mar Chiquita, which has been
      declared as a Biosphere Reserve by the Man and Biosphere Reserve Program from
      UNESCO. Its margins present populations of Chasmagnathus granulatus, a
      semiterrestrial crab distributed along wide salinity gradients that plays an
      important role as a key species within the corresponding trophic web. Dissolved
      cadmium (Cd) and zinc (Zn) concentrations present in this ecosystem were
      determined. Cadmium concentrations ranged between n.d. and 0.82 mug/L and zinc
      levels ranged between n.d. and 1224.38 mug/L within the mentioned coastal lagoon.
      Cd and Zn acute semistatic toxicity bioassays were carried out for 96 h on
      juvenile crabs of C. granulatus. LC(50) 96-h values were 2.24 mg Cd(2+)/L and
      7.07 mg Zn(2+)/L at 5 psu, and 15.42 mg Cd(2+)/L and 11.41 mg Zn(2+)/L at 25 psu.
      Higher salinities resulted in lower metal toxicity. This effect was stronger for
      Cd than for Zn. C. granulatus juveniles LC(50) 96-h values determined for Cd were
      three to four orders of magnitude higher than the corresponding dissolved metal
      concentrations in the Mar Chiquita coastal lagoon; nevertheless, those Zn values
      determined were similar to several ones corresponding to natural water samples.

PMID- 18071783
TI  - Effects of transcatheter closure of Fontan fenestration on exercise tolerance.
      kidecho@yahoo.com.
AB  - Baffle fenestration is associated with a significantly better outcome in standard
      and high-risk patients undergoing completion of Fontan. We report the effects of
      subsequent transcatheter closure of fenestration on exercise capacity and oxygen
      saturation. Sixteen patients with a mean age of 10.3 years underwent Amplatzer
      septal occluder (ASO) device transcatheter closure of Fontan fenestration. All
      had a fenestrated Fontan operation 6 month to 8 years prior to the procedure. A
      stress test was performed before and after device closure of fenestration in 14
      patients (2 patients did not tolerate stress test before the procedure). The
      fenestrations in all patients were successfully occluded with the use of the
      Amplatzer device occluder. No complications occurred during or after the
      procedure. O2 saturation increased from a mean 85.1 +/- 7.89% to 94.5 +/- 3.63%
      (p < 0.01) at rest and from 66.2 +/- 12.86% to 87.2 +/- 8.64% (p < 0.01)
      following exercise. Exercise duration has also increased from 8.22 +/- 2.74 min
      to 10.29 +/- 1.91 min (p < 0.05). Transcatheter closure of Fontan fenestration
      increases the duration of exercise capacity and increases O2 saturation at rest
      and after exercise.

PMID- 18071789
TI  - TIPSS procedure in the treatment of a single patient after recent heart
      transplantation because of refractory ascites due to cardiac cirrhosis.
AB  - We present the case of a female patient with arrhythmogenic dysplasia of the
      right ventricle who evolved to refractory heart failure, ascites, and peripheral
      edema. As a result, heart transplantation was performed. Subsequently, refractory
      ascites impaired the patient's respiratory function, resulting in prolonged
      mechanical ventilation. She was successfully treated with transjugular
      intrahepatic portosystemic shunt (TIPSS) placement, which allowed satisfactory
      weaning of ventilatory support.

PMID- 18071790
TI  - MDCT anatomic assessment of right inferior phrenic artery origin related to
      potential supply to hepatocellular carcinoma and its embolization.
AB  - PURPOSE: To prospectively assess the anatomic variation of the right inferior
      phrenic artery (RIPA) origin with multidetector computed tomography (MDCT) scans
      in relation to the technical and angiographic findings during transcatheter
      arterial embolization of hepatocellular carcinoma (HCC). METHODS: Two hundred
      patients with hepatocellular carcinomas were examined with 16-section CT during
      the arterial phase. The anatomy of the inferior phrenic arteries was recorded,
      with particular reference to their origin. All patients with subcapsular HCC
      located at segments VII and VIII underwent arteriography of the RIPA with
      subsequent embolization if neoplastic supply was detected. RESULTS: The RIPA
      origin was detected in all cases (sensitivity 100%), while the left inferior
      phrenic artery origin was detected in 187 cases (sensitivity 93.5%). RIPAs
      originated from the aorta (49%), celiac trunk (41%), right renal artery (5.5%),
      left gastric artery (4%), and proper hepatic artery (0.5%), with 13 types of
      combinations with the left IPA. Twenty-nine patients showed subcapsular HCCs in
      segments VII and VIII and all but one underwent RIPA selective angiography,
      followed by embolization in 7 cases. CONCLUSION: MDCT assesses well the anatomy
      of RIPAs, which is fundamental for planning subsequent cannulation and
      embolization of extrahepatic RIPA supply to HCC.

PMID- 18071791
TI  - Production and regulation of cuticle-degrading proteases from Beauveria bassiana
      in the presence of Rhammatocerus schistocercoides cuticle.
AB  - Extracellular proteases have been shown to be virulence factors in fungal
      pathogenicity toward insects. We examined the production of extracellular
      proteases, subtilisin-like activity (Pr1) and trypsin-like activity (Pr2), by
      Beauveria bassiana CG425, which is a fungus of interest for control of the
      grasshopper Rhammatocerus schistocercoides. To access the role of these proteases
      during infection of R. schistocercoides, we analyzed their secretion during
      fungus growth either in nitrate-medium or in cuticle-containing medium
      supplemented with different amino acids. The enhancing effect of cuticle on Pr1
      and Pr2 production suggests that these protease types may be specifically induced
      by components of the grasshopper cuticle. In medium supplemented with methionine
      a high level of Pr1 was observed. The remaining amino acids tested did not induce
      the protease to the levels seen with cuticle. The amino acid methionine seems to
      play a regulatory role in Pr1 secretion by B. bassiana, since both induction and
      repression seem to be dependent on the concentration of the amino acid present in
      the culture medium.

PMID- 18071792
TI  - Origin of the sound components during pharyngeal swallowing in normal subjects.
AB  - The aim of this study was to identify the origin of swallowing sound components
      by using modern techniques that can provide numeric, synchronized acoustic
      radiologic data. We enrolled 15 volunteer subjects (10 men and 5 women, average
      age = 29.5 +/- 8 years) and used an X-ray camera connected to a video acquisition
      card to obtain synchronized acoustic-radiologic data (25 images/s). The subjects
      were asked to swallow 10 ml of a barium suspension. Each sound component was
      associated with a specific position of the bolus and the anatomic structure that
      was moving. The average duration of the pharyngeal sound was 690 +/- 162 ms. The
      durations of the laryngeal ascension sound and the laryngeal release sound were
      significantly different (72 +/- 38 ms and 106 +/- 47 ms, p < 0.001). The upper
      sphincter opening sound was present in 100% of the recordings. Its duration was
      185 +/- 103 ms and was significantly different from the two other sounds. The
      duration of the first interval was 108 +/- 44 ms and the duration of the second
      was 236 +/- 139 ms. This study allowed us to determine the origin of the three
      main sound components of the pharyngeal swallowing sound with respect to
      movements in anatomic structures and the different bolus positions.

PMID- 18071794
TI  - Retraction by surface ferromagnetisation of target tissues: preliminary studies
      on feasibility of magnetic retraction for endoscopic surgery.
AB  - BACKGROUND: Magnetic retraction has potential advantages over existing direct
      physical retraction means (e.g., forceps) in terms of providing complete
      atraumatic retraction, avoiding tumour cell exfoliation as well as offering the
      possibility of noncontact retraction. This paper describes a pilot study of
      surface magnetic retraction of the gastric mucosa to facilitate resection.
      METHODS: Fifteen porcine stomach specimens were used in this pilot study. The
      uniaxial tensile properties of retracted mucosa were initially studied using a
      tensiometer. Magnetic media of ferromagnetic microparticles (stainless steel 410)
      dispersed in cyanoacrylate liquid were prepared at four different concentrations,
      and a neodymium permanent magnet was used to magnetically retract the media. The
      media was finally surface-glued to the target mucosa for performing a simulated
      surgical procedure. RESULTS: The force measurement data show that the retraction
      forces increased as the concentrations of microparticles and magnetic media
      volumes increased. A magnetic media concentration of 2 g/mL was most suitable
      since it offered sufficient retraction force from a small volume of applied
      media, e.g., the observed magnetic forces exerted on 50 microL of media were 1.42
      N by a 3-mm magnet and 3.75 N by a 6-mm magnet, respectively, both being more
      than sufficient for the mucosal retraction. The additional forces required for
      dissection with four alternative instruments, i.e., electrosurgery hook, snares,
      scalpel or scissors, were also measured, e.g., the total force required to
      retract up to 10 mm and resect the mucosa with snares was 0.36 +/- 0.17 N. In a
      simulated surgical procedure (resection of gastric mucosa with glued magnetic
      medium) retraction by the magnet allowed resection of the tented mucosa by an
      electrosurgical snare. CONCLUSION: Surface ferromagnetisation of target mucosal
      tissues could enable magnetic retraction for endoscopic surgery.

PMID- 18071793
TI  - Laparoscopic partial posterior (Toupet) fundoplication improves esophageal bolus
      propagation on scintigraphy.
AB  - BACKGROUND: Impaired esophageal clearance is important in the pathogenesis of
      gastroesophageal reflux disease (GERD). It is unknown whether esophageal
      clearance improves following antireflux surgery. The aim of this study was to
      investigate the effect of laparoscopic Nissen fundoplication (NF), laparoscopic
      partial posterior (Toupet) fundoplication (PPF) or medical therapy on esophageal
      clearance. METHODS: This was a prospective nonrandomized crossover study. Sixty
      patients were evaluated with endoscopy, esophageal manometry, radionuclide
      scanning of esophageal emptying, and assessment of symptoms prior to surgery or
      medical therapy and 6 months after treatment. In 20 GERD patients with normal
      esophageal peristalsis an NF was performed, in 20 patients with impaired
      esophageal peristalsis a PPF was chosen, and 20 patients received proton-pump
      inhibitor (PPI) treatment. RESULTS: On endoscopy, esophagitis had resolved in all
      patients after surgery; two patients with medical therapy still had esophagitis.
      On manometry, a significant improvement of lower esophageal sphincter competence
      was seen in both surgical groups. LES relaxation was complete after PPF, but
      incomplete after NF. Esophageal peristalsis did not improve after medical
      therapy, was significantly improved after PPF, but had worsened after NF. On
      scintigraphic esophageal emptying for solid meals, there was no improvement after
      medical therapy but a significant improvement after PPF. A significant
      deterioration of esophageal emptying was observed after NF. There was a strong
      correlation between scintigraphic and manometric evaluation of peristalsis
      preoperatively (r(s) = -0.87, p < 0.05) and postoperatively (r(s) = -0.82, p <
      0.05). There was no change in dysphagia after medical therapy and after NF but a
      significant improvement after PPF. Globus sensation was significantly improved
      after PPF but did not change after medical therapy or NF. Postprandial bloating
      and inability to belch were significantly more common after NF than after PPF.
      CONCLUSION: Laparoscopic partial posterior (Toupet) fundoplication can restore a
      preoperatively defective esophageal bolus propagation on scintigraphy with the
      same antireflux effect as the laparoscopic Nissen fundoplication, but with lower
      side-effects.

PMID- 18071796
TI  - Laparoscopic appendectomy without clip or ligature. An experimental study.
AB  - BACKGROUND: We aimed to test the efficacy and safety of closure of the
      appendeceal stump with only laparoscopic bipolar electrocautery in rats. METHODS:
      In this study, 40 female Wistar-Albino rats were used. In group I (n = 10),
      appendix vermiformis, approximately 1 cm in width, was completely ligated with
      3/0 silk suture close to cecum, and removed. In group II (n = 20) and group III
      (n = 10), the appendeceal stump was coagulated by bipolar cautery. The
      coagulation of 70 mA took 10 s, and was repeated one more time. The stump was
      divided, and checked to ensure complete occlusion. Groups I and II underwent
      relaparotomy at 15 days, cecum was taken out, and the burst pressure of the stump
      was measured. Group III did not undergo relaparotomy; the burst pressure was
      measured during the first laparotomy. RESULTS: All rats survived. At
      relaparotomy, no intra-abdominal complications were detected, including
      intestinal obstruction, abscess, and leakage. Omentum and fatty tissue of uterus
      was adhered to the appendix stump in group I, but only fatty tissue of uterus was
      adhered on the stump in group II. Although the intracecal pressure reached 30
      cmH(2)O, at which pressure the cecum was highly stretched, ligated (group I) or
      coagulated (group II) stumps did not burst or opened. In group III, the burst or
      opening pressure of the stump (11.2 +/- 2.7 cmH(2)O) was significantly lower than
      in groups I and II (p < 0.001). Of group II rats, 80% had complete epithelial
      regeneration at the coagulated stump sites in contrast to ligated rats (p <
      0.001) with severe inflammatory changes, abscess, and necrosis. CONCLUSIONS: At
      late course, coagulated stumps did not allow the leakage or burst, unlike ligated
      stumps. However, coagulation of the stump seemed to contribute more to epithelial
      healing. This experimental model suggests that the closure of the stump with only
      bipolar coagulation was a safe and feasible method.

PMID- 18071797
TI  - Endoscopic sphincterotomy and interval cholecystectomy are reasonable
      alternatives to index cholecystectomy in severe acute gallstone pancreatitis
      (GSP).
AB  - BACKGROUND: UK guidelines for gallstone pancreatitis (GSP) advocate definitive
      treatment during the index admission, or within 2 weeks of discharge. However,
      this target may not always be achievable. This study reviewed current management
      of GSP in a university hospital and evaluated the risk associated with interval
      cholecystectomy. METHODS: All patients that presented with GSP over a 4-year
      period (2002-2005) were stratified for disease severity (APACHE II). Patient
      demographics, time to definitive therapy [index cholecystectomy; endoscopic
      sphincterotomy (ES); Interval cholecystectomy], and readmission rates were
      analysed retrospectively. RESULTS: 100 patients admitted with GSP. Disease
      severity was mild in 54 patients and severe in 46 patients. Twenty-two patients
      unsuitable for surgery underwent ES as definitive treatment with no readmissions.
      Seventy-eight patients underwent cholecystectomy, of which 40 (58%) had an index
      cholecystectomy, and 38 (42%) an interval cholecystectomy. Only 10 patients with
      severe GSP had an index cholecystectomy, whilst 30 were readmitted for Interval
      cholecystectomy (p = 0.04). The median APACHE score was 4 [standard deviation
      (SD) 3.8] for index cholecystectomy and 8 (SD 2.6) for Interval cholecystectomy
      (p < 0.05). Median time (range) to surgery was 7.5 (2-30) days for index
      cholecystectomy and 63 (13-210) days for Interval cholecystectomy. Fifty percent
      (19/38) of patients with GSP had ES prior to discharge for interval
      cholecystectomy. Two (5%) patients were readmitted: with acute cholecystitis (n =
      1) and acute pancreatitis (n = 1) , whilst awaiting interval cholecystectomy. No
      mortality was noted in the Index or Interval group. CONCLUSIONS: This study
      demonstrates that overall 62% (22 endoscopic sphincterotomy and 40 index
      cholecystectomy) of patients with GSP have definitive therapy during the Index
      admission. However, surgery was deferred in the majority (n = 30) of patients
      with severe GSP, and 19/30 underwent ES prior to discharge. ES and interval
      cholecystectomy in severe GSP is associated with minimal morbidity and
      readmission rates, and is considered a reasonable alternative to an index
      cholecystectomy in patients with severe GSP.

PMID- 18071798
TI  - The role of laparoscopic adrenalectomy for adrenal tumours of 6 cm or greater.
AB  - BACKGROUND: Laparoscopic adrenalectomy (LA) has been shown to reduce hospital
      stay and morbidity when compared to open adrenalectomy (OA). It is uncertain if
      the laparoscopic resection of large (>/=6 cm) potentially malignant adrenal
      tumours is appropriate due to concern over incomplete resection and local
      recurrence. The aim of the present study was to compare the outcomes of LA for
      tumours >/=6 cm with those < 6 cm. METHODS: Details of all patients referred with
      adrenal tumours between January 1999 and January 2006 had been recorded
      prospectively on a database. LA was performed using a lateral transabdominal
      approach. Contraindications to LA were local invasion requiring en bloc resection
      of adjacent organs or the requirement of additional open procedures. RESULTS: 103
      patients were referred for adrenal resection. Three with metastatic adrenal
      carcinoma and two with severe cardiorespiratory disease were deemed unsuitable
      for operation. One hundred and eleven adrenalectomies were performed: 101 LAs and
      10 OAs. Thirty-nine LA were for tumours >/=6 cm while nine OA were for tumours
      >/=6 cm. There were no significant differences between the median total
      anaesthetic time, postoperative complications or postoperative stay for patients
      undergoing LA for tumours >/=6 cm versus tumours <6 cm. Of the six conversions,
      five were performed for adrenal tumours >/=6 cm [local invasion (n = 3),
      adhesions (n = 1), primary renal carcinoma (n = 1)]. All tumours in the LA group
      were resected with clear margins and at a median follow up of 50 months (range 38
      74 months). There has been no evidence of local recurrence. CONCLUSIONS: In the
      absence of local invasion, the outcomes of laparoscopic adrenalectomy for
      patients with tumours >/=6 cm were comparable to those with tumours <6 cm. This
      has helped confirm a policy of initial laparoscopic resection for all noninvasive
      adrenal tumours can be applied safely.

PMID- 18071799
TI  - Laparoscopic common bile duct exploration after failed endoscopic stone
      extraction.
AB  - BACKGROUND: Our objective was to present the technical aspects and results of
      laparoscopic common bile duct (CBD) exploration following failed endoscopic stone
      extraction. METHOD: From April 1997 to December 2006, 32 patients were referred
      to us after unsuccessful attempts at endoscopic CBD stone extraction.
      Transcholedochal laparoscopic CBD exploration was used in all patients. Previous
      operations, several pathologic entities, and stone impaction were studied as
      potential predictors of failure of the laparoscopic approach. RESULTS: Previous
      operations, cholangitis, anatomic abnormalities, and stone impaction were the
      principal reasons for failure of endoscopic retrograde cholangiopancreatography
      (ERCP). Stone extraction under direct laparoscopic choledochotomy was achieved in
      20 of 31 patients (64.51%). Biliary stents were inserted in 7 patients (21.8%)
      and T tubes were placed in 21 patients (65.6%). Five laparoscopic
      choledochoduodenostomies were performed. There were 11 conversions to open
      surgery. Morbidity was 12.5%. CONCLUSIONS: Laparoscopic choledochotomy is an
      efficacious procedure in dealing with unsuccessful endoscopic CBD clearance.

PMID- 18071800
TI  - Complications and frequency of redo antireflux surgery in Denmark: a nationwide
      study, 1997-2005.
AB  - BACKGROUND: Outcomes after redo fundoplication (RF) in recurrent gastroesophageal
      reflux disease (GERD) are debatable, and they may include lower success rates
      with higher postoperative morbidity and mortality than outcomes after primary
      fundoplication (PF). However, data from large, nationwide studies are not
      available. Accordingly, the aim of the present study was to evaluate nationwide
      Danish data on RF in a nine-year period. METHOD: Data in the period from 1997
      through 2005 were extracted from the National Patient Register. The following
      information was procured: frequency of RF, rate of conversion to open surgery,
      rate of complications requiring reoperation, and 30-day mortality. Data for RF
      were compared to PF. RESULTS: A total of 2589 fundoplications were performed in
      2465 patients. Thus, 113 patients underwent a total of 124 RF (RF rate = 5.0%).
      Most RF (84.7%) were performed at high-volume departments. Patients who underwent
      RF were converted to open surgery more often (16.1% vs. 6.1% in PF) (P < 0.0001).
      The median postoperative hospital stay was 3 days after RF and 2 days after PF (P
      = 0.96). Following RF 1.6% of the patients had complications requiring surgery
      compared with 1.3% after PF (P = 0.79), and 30-day mortality was 0.81% after RF
      compared with 0.45% after PF (P = 0.57). CONCLUSION: This nationwide Danish study
      showed a low rate of redo fundoplication and a similar morbidity and mortality
      rate after redo surgery compared with that of primary surgery.

PMID- 18071801
TI  - Laparoscopically assisted colectomy: a study of risk factors and predictors of
      open conversion.
AB  - BACKGROUND: Conversion to an open procedure during laparoscopically assisted
      colorectal resection may be necessary because of technical, patient, or
      pathologic factors. Recent literature has indicated that converted patients may
      have poorer outcomes than those undergoing open or completed laparoscopically
      assisted procedure. This study aimed to audit the authors' experience with
      laparoscopically assisted colectomy and to assess the clinical outcomes of
      patients undergoing conversion. METHODS: All laparoscopic right hemicolectomies
      or anterior resections performed at seven South Australian hospitals from 1997 to
      2006 were reviewed. Data pertaining to patient sex, age, American Society of
      Anesthesiology (ASA) score, pathology, operative outcomes including operating
      time, conversion, reason for conversion, length of hospital stay, and intra- and
      postoperative complications were analyzed. RESULTS: Laparoscopic anterior
      resection had a higher rate of open conversion than laparoscopic right
      hemicolectomy (18.7% vs 10.4%; p = 0.028). In the right hemicolectomy group, none
      of the investigated risk factors for conversion were statistically significant,
      and the morbidity rates for the two groups were similar. The median hospital stay
      was significantly longer in the anterior resection group (p < 0.001), and the
      wound morbidity rate was higher in the converted group (12.8% vs 3.0%; p =
      0.022). Age older than 75 years and a high ASA status were independent risk
      factors for conversion in anterior resection. CONCLUSIONS: Conversion of
      laparoscopic anterior resection to open procedure is associated with higher wound
      morbidity and a longer hospital stay. The authors recommend that surgeons
      carefully consider the selection of patients 75 years of age or older and high
      ASA status for laparoscopic anterior resection.

PMID- 18071802
TI  - Ultrasound-guided radiofrequency-assisted segmental arterioportal vascular
      occlusion in laparoscopic segmental liver resection.
AB  - BACKGROUND: Studies have shown laparoscopic liver resection to be feasible and
      safe. Segmental hepatectomy is appealing because it allows a reduction of
      intraoperative blood loss and blood replacement by dividing tissues along the
      anatomic planes. However, an effective technique that allows the closure of
      segmental vessels during systematic segmentectomies before resection still is
      lacking in laparoscopic surgery. METHODS: A simple technique guided by
      intraoperative ultrasound to facilitate laparoscopic liver segmentectomies is
      described. Coagulative desiccation of the vessels feeding the segment to be
      resected was induced by introduction of a "cooled-tip" radiofrequency electrode
      percutaneously under intraoperative ultrasound guidance at the level of the
      vessels. The intrahepatic parenchymal change induced by the radiofrequency was
      monitored using intraoperative ultrasound. After the application of energy to
      destroy the vessels feeding that segment, an area of marked discoloration on the
      surface of the liver became obvious. Liver parenchymal transection followed
      without any form of hepatic inflow occlusion. RESULTS: For this study, 10
      patients underwent a segmental resection using the described technique. The
      resection time ranged from 40 to 60 min including the time required to destroy
      the feeding vessels with radiofrequency. The intraoperative blood loss was less
      than 50 ml and did not necessitate intra- or postoperative blood transfusion. The
      surgical margins of the specimen were free of disease. There was no morbidity or
      mortality. CONCLUSIONS: The preliminary experience shows that the reported
      technique is safe and effective, with the potential to make even difficult
      laparoscopic liver segmentectomies for segments such as VII and VIII, easier to
      manage.

PMID- 18071803
TI  - Pain sensation and neuromuscular stimulation during argon plasma coagulation in
      gastrointestinal endoscopy.
AB  - BACKGROUND: Argon plasma coagulation (APC) is a thermal coagulation technique
      that uses ionized argon for contact-free transmission of high-frequency
      electrical current to tissue. Prospective data on complications with the new APC
      2 (VIO) system are lacking. METHODS: A prospective trial was conducted with 152
      patients treated for various gastrointestinal diseases using three modes of the
      APC-2. The study aimed to assess complications, focusing on the pain and
      neuromuscular stimulation (NMS) experienced during and after treatment. Patients
      reported pain and NMS using a scale ranging from 0 to 10 and were interviewed for
      symptoms such as tingling, paresthesia, muscle pain, and cramping or twitching.
      The endoscopists also graded NMS using a separate questionnaire. RESULTS: A total
      of 85 males and 67 females (median age, 66 years) were enrolled in the study. All
      APC therapies were completed successfully. Two peri-interventional perforations
      were recorded. Of the 152 patients, 26 (17%) reported pain sensation during or
      after APC. The median pain sensation reported by the patients on the standardized
      scale was 3.7. The findings showed NMS in 14 (9.2%) of the 152 patients.
      Significantly more NMS events were seen with pulsed APC than with forced or
      precise APC. Additional risk factors for NMS were gender (female) and type of
      sedation (combination midazolam and pethidine). No complications were noted among
      patients with intracardiac defibrillators or cardiac pacemakers. CONCLUSIONS:
      According to the findings, APC may be associated with minor complications such as
      pain sensation and NMS. These complications were rarely seen, but occurred more
      often with pulsed APC than with forced or precise APC. Physicians should be aware
      of these complications.

PMID- 18071804
TI  - The use of laparoscopic subtotal cholecystectomy for complicated cholelithiasis.
AB  - BACKGROUND: The risk of damage to the bile duct and structures in the hilum of
      the liver is significant when Calot's triangle cannot be safely dissected during
      laparoscopic cholecystectomy, and conversion to an open procedure often is
      performed. This is more common during emergency surgery, but may not render the
      procedure any easier. Traditionally, open subtotal cholecystectomy was performed,
      but with the advent of laparoscopic surgery, this has fallen from favor. The
      authors report their experience using laparoscopic subtotal cholecystectomy to
      avoid bile duct injury and conversion in difficult cases. METHODS: Laparoscopic
      subtotal cholecystectomy, performed when the cystic duct cannot be identified
      safely, consists of resecting the anterior wall of the gallbladder, removing all
      stones, and placing a large drain into Hartmann's pouch. The notes for all
      patients who underwent a laparoscopic subtotal cholecystectomy between 1
      September 2001 and 31 December 2004 were retrospectively analyzed. RESULTS:
      Subtotal cholecystectomy was performed in 26 cases including 13 emergency and 13
      elective procedures. The median age of the patients (15 women and 11 men) was 68
      years (range, 36-86 years). The indications were severe fibrosis in 16 cases,
      inflammatory mass or empyema in 8 cases, and gangrenous gallbladder or
      perforation in 2 cases. The median postoperative inpatient stay was 5 days
      (range, 2-26 days). Five patients underwent postoperative endoscopic retrograde
      cholangiopancreatography: four for persistent biliary leak and one for a retained
      common bile duct stone. One patient required laparotomy for subphrenic abscess,
      and one patient (American Society of Anesthesiology [ASA] grade 4, presenting
      with biliary peritonitis) died 2 days postoperatively. One patient required a
      subsequent completion laparoscopic cholecystectomy for a retained gallstone. One
      patient had a chest infection, and two patients experienced port-site hernias.
      CONCLUSIONS: Laparoscopic subtotal cholecystectomy is a viable procedure during
      cholecystectomy in which Calot's triangle cannot be dissected. It averts the need
      for a laparotomy.

PMID- 18071805
TI  - Roux-en-Y gastric bypass procedure performed with the da Vinci robot system: is
      it worth it?
AB  - BACKGROUND: The Roux-en-Y gastric bypass procedure (RYGBP) is in many countries
      the gold standard for obtaining long-lasting weight reduction and improvement of
      obesity-related comorbidities. However, performing this operation by standard
      laparoscopic techniques requires important surgical skills because of the
      anastomoses involved. The da Vinci surgical robot system with its enhanced
      degrees of freedom in motion and three-dimensional vision is designed to overcome
      the difficulties encountered in traditional laparoscopic surgery with suturing
      and delicate tissue handling. METHODS: For this study, 45 patients (9 men) with a
      mean body mass index (BMI) of 44.2 (range, 35.1-55.4) underwent RYGBP with the
      aid of the da Vinci robot system. They were compared with 45 consecutive patients
      with a mean BMI of 43.9 (range, 35.1-56.2) who underwent a laparoscopic RYGBP by
      the same surgeon during the same period. RESULTS: Overall, the total operating
      time was shorter for the laparoscopic cases (127 vs 212 min; p < 0.05). However,
      the last 10 robotic cases were performed in the same time span as the
      laparoscopic cases (136 vs 127 min). The total robotic setup time remained
      constant at about 30 min. There were no differences in postoperative
      complications between the two groups in terms of anastomotic leakage or stenosis.
      In the robotic group, more conversions to open surgery were noted. Early in the
      study, four patients (9%) had to undergo conversion to standard laparoscopic
      techniques due to inadequate setup of the robotic arms. Five patients (11%),
      however, had to undergo conversion to open surgery because of intestinal
      laceration during manipulation of the intestines with the robotic instruments.
      The costs were higher for robotic surgery than for standard laparoscopic RYGBP,
      mainly because of the extra equipment used, such as ultrasonic devices.
      CONCLUSION: The RYGBP procedure can be performed safely with the da Vinci robot
      after a learning curve of about 35 cases. At this writing, however, it is not
      clear whether the da Vinci system offers a real advantage over standard
      laparoscopic techniques.

PMID- 18071806
TI  - Minimally invasive esophagectomy for cancer: laparoscopic transhiatal procedure
      or thoracoscopy in prone position followed by laparoscopy?
AB  - BACKGROUND: Minimally invasive esophagectomy is rapidly emerging as a suitable
      surgical alternative to the open technique. This retrospective comparative study
      aimed to compare two minimally invasive techniques for esophagectomy: transhiatal
      laparoscopy with intrathoracic or cervical anastomosis (group A) and right
      thoracoscopy in prone position followed by laparoscopy and left cervicotomy
      (group B) performed by the same surgeon (G.B.C.). The operative time,
      perioperative blood loss, intensive care and total hospital stays, peri- and
      postoperative morbidity, in-hospital mortality, number of lymph nodes dissected,
      and survival were the outcome measures. METHODS: Between April 1999 and August
      2005, 24 patients (group A) and 15 patients (group B) underwent minimally
      invasive esophagectomy for cancer in the authors' department. Their median age
      was 61 years in group A and 61 years in group B. Preoperatively, the endoscopic
      location of the tumor was in the upper third in 2 cases (1 vs 1), the middle
      third in 11 cases (7 vs 4), and the lower third in 26 cases (16 vs 10). Two
      patients in each group received neoadjuvant chemo- and radiotherapy. One patient
      (group A) and two patients (group B) received only neoadjuvant chemotherapy, and
      three patients (group A) received only neoadjuvant radiotherapy. RESULTS: The
      median operative time was 300 min (range, 240-420 min) in group A and 377 min
      (range, 240-540 min) in group B (nonsignificant difference [NS]). The median
      perioperative bleeding was 325 ml (range, 100-800 ml) in group A and 700 ml
      (range, 100-2,400 ml) in group B (NS). The perioperative complications included
      one splenectomy in each group and one conversion to thoracotomy in group B. The
      postoperative medical complications totaled three in group A and six in group B.
      The postoperative surgical complications included one hemoperitoneum, one
      pneumothorax, five anastomotic leaks, and two recurrent laryngeal nerve paralyses
      in group A and two tracheal necroses, four anastomotic leaks, one colic fistula,
      and three recurrent laryngeal nerve paralyses in group B. The median intensive
      care unit (ICU) stay was 5 days (range, 2-70 days) for group A and 5 days (range,
      1-180 days) for group B (NS). The median hospital stay was 12 days (range, 7-98
      days) for group A and 14 days (range, 7-480 days) for group B (p = 0.05). The
      early mortality rate was 0%. All the specimens were free of disease. The median
      number of mediastinal/periesophageal lymph nodes was 3 (range, 1-10) for group A
      and 4 (range, 2-13) for group B (NS), and the median number of celiac/perigastric
      lymph nodes was 11 (range, 2-31) for group A and 10 (range, 3-22) for group B
      (NS). After a median follow-up period of 42.4 months (range, 2-84 months) for
      group A and 19.1 months (range, 1.5-34 months) for group B, 12 patients in group
      A died after a median period of 22 months (range, 2-55 months), and 7 patients in
      group B died after a median time of 15 months (range, 1.5-23 months).
      CONCLUSIONS: This retrospective comparative study showed that minimally invasive
      esophagectomy performed by thoracoscopy in the prone position is comparable with
      laparoscopic transhiatal esophagectomy in terms of the significant postoperative
      and survival outcomes.

PMID- 18071807
TI  - Mesh erosion following prosthetic hiatal closure.

PMID- 18071808
TI  - Nonsurgical skills do not predict baseline scores in inanimate box or virtual
      reality trainers.
AB  - INTRODUCTION: Laparoscopic basic skills are best trained in the nonclinical
      setting. Box trainers and virtual-reality trainers have been shown to be useful
      in training laparoscopic skills. Certain nonsurgical skills may predict baseline
      skills in these trainers. This study tested the hypothesis that baseline scores
      could be predicted in inanimate box trainers and virtual-reality trainers by
      nonsurgical skills. METHODS: Only preclinical medical students were included in
      the study. All students were given a survey ascertaining if they played computer
      games, typed, sew, played a musical instrument, and utilized chopsticks. Students
      utilized a box trainer (BT) and/or virtual-reality trainer (VR). Nonparametric
      two-tailed Mann-Whitney tests were utilized to compare students that possessed
      certain nonsurgical skills versus those who did not. RESULTS: There were 18
      students in the VR group and 33 students in the BT group. In the VR group,
      students who played computer games, typed, utilized chopsticks, or played a
      musical instrument had better scores and fewer errors than those who did not but
      this did not reach statistical significance in any comparison (p = NS). In the BT
      group, none of the nonsurgical skills predicted times or errors. Males performed
      better than females in the VR group (p < 0.001); but this gender discrepancy was
      not seen in the BT group. CONCLUSIONS: Nonsurgical skills do not predict baseline
      scores in either trainer. The gender differences in VR training need to be
      further explored.

PMID- 18071809
TI  - Identification of significant difficulty of selective deep cannulation by a
      simple predictive model: an endoscopic scale for teaching ERCP.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced
      endoscopic procedure associated with a risk of serious complications. This cohort
      study was designed to assess the accuracy of an endoscopic method aimed at
      discriminating procedures eligible to teach ERCP: patients with and without
      significant difficulty of selective deep cannulation (DSDC). METHODS: Clinically
      relevant variables were analyzed in a cohort of 400 consecutive patients
      (estimation group = 250 patients; validation group = 150 patients) who underwent
      an ERCP procedure. RESULTS: Multivariate analysis identified fixated duodenum,
      inflamed duodenum, soft major papilla, previous biliary surgery, and papilla with
      ectopion as independent predictors of DSDC. We constructed a model and a score
      system combining these five variables. The area under the ROC curve was 0.81 for
      the estimation group and 0.80 for the validation group. Using the best cutoff
      score (> 1.63), absence of significant DSDC could be excluded with high accuracy
      (negative predictive value = 89.2%) in 111 (44.4%) of 250 patients. Similarly, it
      could be excluded with the same certainty in 77 (51.3%) of the 150 patients in
      the validation group. CONCLUSIONS: A combination of easily accessible variables
      accurately predicts the absence of significant DSDC in half the patients who
      underwent the ERCP procedure. This score system discriminates procedures eligible
      to teach ERCP.

PMID- 18071810
TI  - Laparoscopic surgery for colorectal cancer: safe and effective? - A systematic
      review.
AB  - OBJECTIVE: To determine the clinical effectiveness of laparoscopic and
      laparoscopically assisted surgery in comparison with open surgery for the
      treatment of colorectal cancer. BACKGROUND: Open resection is the standard method
      for surgical removal of primary colorectal tumours. However, there is significant
      morbidity associated with this procedure. Laparoscopic resection (LR) is
      technically more difficult but may overcome problems associated with open
      resections (OR). METHODS: Systematic review and meta-analysis of short- and long
      term data from randomised controlled trials (RCTs) comparing LS with OR. RESULTS:
      Highly sensitive searches of nine databases identified 19 primary RCTs describing
      data from over 4,500 participants. Length of hospital stay is shorter, blood loss
      and pain are less, and return to usual activities is likely to be faster after LR
      than after OR, but duration of operation is longer. Lymph node retrieval,
      completeness of resection and quality of life do not appear to differ. No
      statistically significant differences were observed in rates of anastomotic
      leakage, abdominal wound breakdown, incisional hernia, wound and urinary tract
      infections, operative and 30-day mortality, and recurrences, nor in overall and
      disease-free survival up to three years. CONCLUSIONS: LR is associated with a
      quicker recovery in terms of return to usual activities and length of hospital
      stay with no evidence of a difference in complications or long-term outcomes in
      comparison to OR, up to three years postoperatively.

PMID- 18071811
TI  - Visual clues act as a substitute for haptic feedback in robotic surgery.
AB  - OBJECTIVE: The lack of haptic feedback (HF) in robotic surgery is one of the
      major concerns of novice surgeons to that field. The superior visual appearances
      acquired during robotic surgery may give clues that make HF less important.
      METHODS: We surveyed 52 individuals on their perception of HF during robotic
      surgery. The first group of 34 surgically inexperienced people used the da Vinci
      robot for their first time (drylab). The second group included 8 laparoscopic
      surgeons with experience up to a fifth robotic operation. The third group
      included 10 surgical experts with substantial experience (150-650 robotic cases).
      Visual analog assessment was made of perception of HF, how much HF was missed,
      how much the absence of HF impaired the operators' level of comfort. Robotic
      experts were asked if complications have occurred as a result of a lack of HF.
      RESULTS: Of the first group, 50% reported the perception of HF, as did 55% of the
      second group and 100% of the third group (difference between group 1 and group 3:
      p < 0.05). The first group missed HF for 6.5; the second group for 4.3, and the
      third group for 4 (difference between groups 1 and 3: p < 0.05). The surgical
      experts claimed to have missed HF for 7.2 s when they first started robotic
      surgery (Difference to now: p < 0.05). The lack of HF caused discomfort for the
      first group of 4; for the second group of 4,4, and for the third group of 2,6.
      One complication was reported by the robotic experts as resulting from the lack
      of HF. CONCLUSIONS: The data support the conclusion that even beginners quickly
      experience the perception of HF when performing robotic surgery. With more
      experience, perception of HF and the level of comfort with robotic surgery
      increases significantly. This perception of HF makes "real" HF less important and
      demonstrates that its importance is overestimated by novices in robotic surgery.

PMID- 18071812
TI  - Endoclipping of iatrogenic colonic perforation to avoid surgery.
AB  - BACKGROUND: Colonoscopy is an established tool for the diagnosis and management
      of colonic and rectal pathology. Even though colonic perforation is rare after
      colonoscopy, it is a serious and typical complication. The definitive management
      remains controversial. Both operative and nonoperative techniques have been
      described in the literature, though the standard treatment for these patients is
      still an operative repair of the perforation site. Recently, endoscopic clip
      application was recommended, particularly for iatrogenic perforations, but less
      is known about the effectiveness of endoluminal repair of colonic perforations
      with clips. METHODS: In this series, 7589 colonoscopies were performed over a 34
      month period in a tertiary-level referral center. Three perforations occurred
      during 5413 diagnostic colonoscopies. Therapeutic colonoscopy was under taken in
      2176 patients, resulting in a total of 27 perforations. Out of 30 patients with
      colonic perforation, five patients underwent operative management and 25 patients
      were subsequently treated nonoperatively. RESULTS: In 27 patients, endoscopic
      application of inert metallic clips was used for closure of iatrogenic
      perforation. Twenty-five of these patients were treated non-operatively, while
      two patients underwent surgery. The mean postoperative length of hospitalization
      for patients was 12.2 days, compared to 3.5 days for patients treated
      conservatively. CONCLUSIONS: Endoluminal repair of colonic perforations with
      clips and further conservative treatment seems to provide a tool that avoids the
      major additional trauma associated with laparotomy or laparoscopy and minimizes
      the length of hospitalization.

PMID- 18071813
TI  - Simulated laparoscopic operating room crisis: An approach to enhance the surgical
      team performance.
AB  - OBJECTIVE: Diminishing human error and improving patient outcomes is the goal of
      task training and simulation experience. The fundamentals of laparoscopic surgery
      (FLS) is a validated tool to assess technical laparoscopic skills. We hypothesize
      that performance in a crisis depends on technical skills and team performance.
      The aim of this study was to develop and validate a high-fidelity simulation
      model of a laparoscopic crisis scenario in a mock endosuite environment. METHODS:
      To establish the feasibility of the model as well as its face and construct
      validity, the scenario evaluated the performances of FLS-certified surgeon
      experts (n = 5) and non-FLS certified novices (n = 5) during a laparoscopic
      crisis scenario, in a mock endosuite, on a simulated abdomen. Likert scale
      questionnaires were used for validity assessments. Groups were compared using
      previously validated rating scales on technical and nontechnical performance.
      Objective outcome measures assessed were: time to diagnose bleeding (TD), time to
      inform the team to convert (TT), and time to conversion to open (TC). SAS
      software was used for statistical analysis. RESULTS: Median scores for face
      validity were 4.29, 4.43, 4.71 (maximum 5) for the FLS, non-FLS, and nursing
      groups, respectively, with an inter-rater reliability of 93%. Although no
      difference was observed in Veress needle safety and laparoscopic equipment set
      up, there was a significant difference between the two groups in their overall
      technical and nontechnical abilities (p < 0.05), specifically in identifying
      bleeding, controlling bleeding, team communication, and team skills. There was a
      trend towards a difference between the two groups for TD, TT, and TC. While
      experts controlled bleeding in a shorter time, they persisted longer
      laparoscopically. CONCLUSIONS: Our evidence suggests that face and construct
      validity are established for a laparoscopic crisis simulation in a mock
      endosuite. Technical and nontechnical performance discrimination is observed
      between novices and experts. This innovative multidisciplinary simulation aims at
      improving error/problem recognition and timely initiation of appropriate and safe
      responses by surgical teams.

PMID- 18071814
TI  - Filtered signal-averaged P-wave duration during pneumoperitoneum in patients
      undergoing laparoscopic cholecystectomy: A reflection of pathophysiological
      cardiac changes.
AB  - BACKGROUND: Induction of pneumoperitoneum (PP) may lead to adverse cardiac
      functions secondary to changes such as decreased venous return and hypercarbia.
      The assessment of cardiac electrical activity by signal averaging may reflect
      various hemodynamic derangements and serve as a prognostic marker for
      arrhythmias. The aim of the study is to examine characteristic
      electrocardiographic changes that may occur during PP, by using signal-averaged P
      wave analysis. METHODS: Twenty healthy (ASA I and II) patients were enrolled in a
      prospective paired control study, and underwent elective laparoscopic
      cholecystectomy. A standard ECG together with computerized filtered signal
      averaged P-wave duration measurement (leads X, Y, Z) were carried out during
      awareness, under anesthesia before and during PP, and after CO(2) evacuation.
      Depth of anesthesia was controlled by bi-spectral index (BIS). RESULTS: An
      increased duration of P-wave was observed during PP in comparison to the
      anesthesia phase before PP (111 versus 115 ms, t-test and Wilcoxon signed rank
      test). A significant increase was also detected in the maximal value of P-wave
      duration between these phases of the operation. The difference in the number of
      patients in whom the duration increased by at least 5 ms was also found to be
      significant. CONCLUSIONS: Primarily, a decreased P-wave duration was expected,
      due to cardiac autonomic sympathetic predominance during PP. Its prolongation
      during PP may reflect some cardiac pathophysiological (structural and functional)
      changes, including influence on cardiac ion channels during depolarization.
      Usually, clinical consequences related to laparoscopic cholecystectomy are
      absent, but clinical awareness should be maintained for cardiac diseased patients
      undergoing prolonged laparoscopic procedures.

PMID- 18071815
TI  - Laparoscopic versus small-incision cholecystectomy: health status in a blind
      randomised trial.
AB  - BACKGROUND: Gallstones are a major cause of morbidity, and cholecystectomy is a
      commonly performed procedure. Minimal invasive procedures, laparoscopic
      cholecystectomy (LC) and small-incision cholecystectomy (SIC), have replaced the
      classical open cholecystectomy. No differences have been found in primary outcome
      measures between LC and SIC, therefore secondary outcome measures have to be
      considered to determine preferences. The aim of our study was to examine health
      status applying evidence-based guidelines in LC and SIC in a randomised trial.
      METHODS: Patients with symptomatic cholecystolithiasis were included in a blind
      randomised trial. Operative procedures, anaesthesia, analgesics and postoperative
      care were standardised in order to limit bias. Questionnaires were filled in
      preoperatively, the first day postoperatively, and at outpatients follow-up at 2,
      6 and 12 weeks. In accordance with evidence-based guidelines, the generic short
      form (SF-36) and the disease-specific gastrointestinal quality-of-life index
      (GIQLI) questionnaires were used in addition to the body image questionnaire
      (BIQ). RESULTS: A total of 257 patients were randomised between LC (120) and SIC
      (137). Analyses were performed according to intention-to-treat (converted
      procedures included) and also distinguishing converted from minimal invasive
      (nonconverted) procedures. Questionnaires were obtained with a response rate
      varying from 87.5% preoperatively to 77.4% three months postoperatively. Except
      for two time-specific measurements in one SF-36 subscale, there were no
      differences between LC and SIC. There were significant differences in several
      subscales in all three questionnaires comparing minimal invasive versus converted
      procedures. CONCLUSIONS: Applying adequate methodological quality and evidence
      based guidelines (by using SF-36 and GIQLI), there are no significant differences
      in health status between LC and SIC.

PMID- 18071816
TI  - The laparoscopic duodenopancreatectomy: the posterior approach.

PMID- 18071817
TI  - Prospective trial comparing contrast swallow, computed tomography and endoscopy
      to identify anastomotic leak following oesophagogastric surgery.
AB  - BACKGROUND: Anastomotic leaks are a major complication of oesophagogastric
      surgery. We compare contrast swallow fluoroscopy, computed tomography (CT) with
      oral contrast and endoscopy in identifying anastomotic leaks following
      oesophagogastric surgery. METHODS: A prospective trial of 38 patients undergoing
      oesophagogastric resection was undertaken with informed consent and institutional
      review board (ethics committee) approval. Patients underwent all three
      investigations (over 24 hours) 1 week postoperatively. RESULTS: Eight (21%) had
      clinically apparent leaks. Three pseudo-leaks were suggested on contrast swallow
      but were confirmed normal on CT and endoscopy. Contrast swallow and CT missed one
      anastomotic leak each. Endoscopy identified anastomotic defects in three
      patients, in whom CT and contrast swallow were either normal or conflicting.
      CONCLUSIONS: Routine tests of anastomotic integrity are unnecessary. When
      clinically suspected, contrast swallow or CT with oral contrast will identify
      most leaks. Endoscopy is useful in cases where there are incongruous results.

PMID- 18071818
TI  - Endoluminal fundoplication by a transoral device for the treatment of GERD: A
      feasibility study.
AB  - BACKGROUND: A new endoluminal fundoplication (ELF) technique performed
      transorally using the EsophyXtrade mark device was evaluated for the treatment of
      gastroesophageal reflux disease (GERD) in a prospective, feasibility clinical
      trial. METHODS: Nineteen patients were enrolled into the study. Inclusion
      criteria were chronic and symptomatic GERD, proton pump inhibitor (PPI)
      dependence, and the absence of esophageal motility disorder. Two patients were
      excluded due to esophageal stricture and a 6 cm hiatal hernia. The median
      duration of GERD symptoms and PPI use in the remaining 17 patients was 10 and 6
      years, respectively. The ELF procedure was designed to partially reconstruct the
      antireflux barrier through the creation of a valve at the gastroesophageal
      junction. RESULTS: The ELF-created valves had a median length of 4 cm (range 3-5
      cm) and circumference of 210 degrees (180-270 degrees ). Adherence of the valves
      to the endoscope was tight (n = 14) or moderate (n = 3). Hiatal hernias present
      in 13 patients (76%) were all reduced. Adverse events were limited to mild or
      moderate pharyngeal irritation and epigastric pain, which resolved spontaneously.
      After 12 months, the ELF valves (n = 16) had a median length of 3 cm (1-4 cm) and
      a circumference of 200 degrees (150-210 degrees ). Eighty-one percent of valves
      retained their tightness. The hiatal hernias present at the baseline remained
      reduced in 62% of patients. The median GERD-HRQL scores improved by 67% (17-6),
      and nine patients (53%) improved their scores by >or=50%. Eighty-two percent of
      patients were satisfied with the outcome of the procedure, 82% remained
      completely off PPIs, and 63% had normal pH. CONCLUSION: The study demonstrated
      technical feasibility and safety of the ELF procedure using the EsophyX device.
      The study also demonstrated maintenance of the anatomical integrity of the ELF
      valves for 12 months and provided preliminary data on ELF efficacy in reducing
      the symptoms and medication use associated with GERD.

PMID- 18071819
TI  - Shape-adaptive DCT for denoising of 3D scalar and tensor valued images.
AB  - During the last ten years or so, diffusion tensor imaging has been used in both
      research and clinical medical applications. To construct the diffusion tensor
      images, a large set of direction sensitive magnetic resonance image (MRI)
      acquisitions are required. These acquisitions in general have a lower signal-to
      noise ratio than conventional MRI acquisitions. In this paper, we discuss
      computationally effective algorithms for noise removal for diffusion tensor
      magnetic resonance imaging (DTI) using the framework of 3-dimensional shape
      adaptive discrete cosine transform. We use local polynomial approximations for
      the selection of homogeneous regions in the DTI data. These regions are
      transformed to the frequency domain by a modified discrete cosine transform. In
      the frequency domain, the noise is removed by thresholding. We perform numerical
      experiments on 3D synthetical MRI and DTI data and real 3D DTI brain data from a
      healthy volunteer. The experiments indicate good performance compared to current
      state-of-the-art methods. The proposed method is well suited for parallelization
      and could thus dramatically improve the computation speed of denoising schemes
      for large scale 3D MRI and DTI.

PMID- 18071821
TI  - The defensive role of volatile emission and extrafloral nectar secretion for lima
      bean in nature.
AB  - Lima bean (Phaseolus lunatus) features two indirect anti-herbivore defenses-
      emission of volatile organic compounds (VOCs) and secretion of extrafloral nectar
      (EFN)--which are both inducible upon herbivore damage. In a previous field study,
      Lima bean benefited from the simultaneous induction of the two defenses, yet it
      remained unclear whether both had contributed to plant protection. Our
      experimental approach aimed at studying the defensive role of both indirect
      defenses simultaneously. Tendrils were sprayed with jasmonic acid (JA) to induce
      both defenses, and performance was compared to that of others that were treated
      with a synthetic blend of either EFN or VOCs. Confirming earlier results, JA
      treatment and application of the VOC mixture induced EFN secretion in treated
      tendrils in quantitatively similar amounts. The composition of the applied
      synthetic blend of EFN was adjusted to match the concentration of EFN secreted
      from JA- and VOC-treated tendrils. Repeated application of either enhanced the
      performance of several fitness-relevant plant parameters such as growth rate and
      flower production. Tendrils treated with JA showed a similar trend, yet some
      fitness-related parameters responded less to this treatment. This suggests a
      minor importance of any putative JA-dependent direct defense traits or higher
      costs of JA-elicited responses as compared to VOCS and EFN, as otherwise JA
      treated tendrils should have outperformed VOC- and EFN-treated tendrils.
      Moreover, the beneficial effect of applying synthetic EFN alone equaled or
      exceeded that of VOCs and JA. Ants were by far the dominant group among the
      arthropods that was attracted to JA-, VOC-, or EFN-treated tendrils. The results
      suggest that EFN plays a more important role as an indirect defense of lima bean
      than VOCs or any other JA-responsive trait.

PMID- 18071820
TI  - An artificial immune-activated neural network applied to brain 3D MRI
      segmentation.
AB  - In this paper, a new neural network model inspired by the biological immune
      system functions is presented. The model, termed Artificial Immune-Activated
      Neural Network (AIANN), extracts classification knowledge from a training data
      set, which is then used to classify input patterns or vectors. The AIANN is based
      on a neuron activation function whose behavior is conceptually modeled after the
      chemical bonds between the receptors and epitopes in the biological immune
      system. The bonding is controlled through an energy measure to ensure accurate
      recognition. The AIANN model was applied to the segmentation of 3-dimensional
      magnetic resonance imaging (MRI) data of the brain and a contextual basis was
      developed for the segmentation problem. Evaluation of the segmentation results
      was performed using both real MRI data obtained from the Center for Morphometric
      Analysis at Massachusetts General Hospital and simulated MRI data generated using
      the McGill University BrainWeb MRI simulator. Experimental results demonstrated
      that the AIANN model attained higher average results than those obtained using
      published methods for real MRI data and simulated MRI data, especially at low
      levels of noise.

PMID- 18071822
TI  - Helikauranoside a, a new bioactive diterpene.
AB  - A new ent-kaurane glucoside, named helikauranoside A (4), was isolated from the
      aerial parts of Helianthus annuus L. together with three known ent-kaurane-type
      diterpenoids: (-)-kaur-16-en-19-oic acid (1), grandifloric acid (2), and
      paniculoside IV (3). The structure of 4 was determined by using a combination of
      1D (1H-NMR and 13C-NMR) and 2D (COSY, HSQC, and HMBC) NMR techniques. Bioactivity
      spectra of isolated compounds were tested by using the etiolated wheat coleoptile
      bioassay in aqueous solutions at concentrations ranging from 10(-3) to 10(-6)M.
      Helikauranoside A (4) was the most active (-84%, 10(-3)M; -56%, 10(-4)M). These
      results suggest that this new compound may be involved in defense mechanisms of
      H. annuus.

PMID- 18071823
TI  - A career in surgical oncology: finding meaning, balance, and personal
      satisfaction.
AB  - The practice of surgical oncology provides opportunities for both personal
      distress as well as personal satisfaction. While many surgical oncologists
      experience career burnout, others derive great meaning and satisfaction from
      their work. In this article, we review the literature on surgeon burnout, discuss
      potential personal and professional consequences, and consider steps individual
      surgeons can take to promote personal and professional satisfaction.

PMID- 18071824
TI  - Fluorescence in situ hybridization and immunohistochemical analysis of p53
      expression in endometrial cancer: prognostic value and relation to ploidy.
AB  - BACKGROUND: Endometrial carcinoma is the most common gynecological malignancy.
      Several molecular biological characteristics have been studied for their
      potential value in patient management. OBJECTIVES: Our objectives were to compare
      p53 immunohistochemical expression with P53 gene status determined by
      fluorescence in situ hybridization (FISH) and to compare these characteristics
      with ploidy and with classical clinical and histological prognostic factors.
      MATERIALS AND METHODS: We reviewed stored specimens from 43 patients with
      endometrial cancer diagnosed in 1999-2004. P53 FISH and immunohistochemistry were
      performed, together with imaging cytometry to calculate DNA ploidy. RESULTS:
      Thirteen of the 43 endometrial carcinomas (30.2%) showed P53 loss of
      heterozygosity (LOH). P53 LOH correlated with the histological type (P = .03) and
      the histological grade (P = .004). Quantitative immunohistochemical expression of
      p53 protein correlated with the histological type (P = .0001). With a cutoff of
      10% of p53-positive cells, p53 overexpression correlated with the histological
      type (P = .003) and grade (P = .0008). No relation was found between P53 LOH or
      immunohistochemical expression and the disease stage, the depth of myometrial
      invasion, lymph node status, lymphovascular space involvement, recurrence, or
      death from cancer. Nondiploid carcinomas showed deeper myometrial invasion than
      diploid carcinomas (P = .01). No relation was observed between ploidy and
      qualitative or semiquantitative p53 expression or P53 LOH. CONCLUSION: In
      endometrial cancer, FISH analysis of P53 status adds no significant prognostic
      information compared with immunohistochemical p53 analysis.

PMID- 18071825
TI  - Indication for endoscopic mucosal resection in early signet ring cell gastric
      cancer.
AB  - BACKGROUND: The aim of this study was to compare the clinicopathological
      characteristics of an early signet ring cell carcinoma (SRC) with an early
      undifferentiated carcinoma (mucinous, poorly differentiated adenocarcinoma) and
      early differentiated carcinoma (well or moderately differentiated tubular
      adenocarcinoma, papillary adenocarcinoma) and find indications for endoscopic
      mucosal resection (EMR) in early SRC. METHODS: 1520 patients with early gastric
      cancer (EGC), who underwent a curative gastrectomy, were analyzed
      retrospectively. Among them, 388 patients with SRC were compared with 253
      patients with undifferentiated carcinoma (UDC) and 879 with a differentiated
      carcinoma (DC). RESULTS: SRC was more common in young female patients than UDC.
      SRC had a tendency to be confined to the mucosa, with smaller size than UDC. The
      lymph node metastasis rate for SRC was lower than that for UDC, but similar to
      that of DC. Multivariate analysis revealed lymph node metastasis (LNM) to be
      associated with the depth of invasion, tumor size, histological type, and
      lymphatic involvement. SRC had no LNM in the case of a mucosal tumor, smaller
      than 2 cm, and in the absence of lymphatic involvement. The prognosis of SRC was
      more favorable than UDC. CONCLUSIONS: Early SRC has different characteristics
      from early UDC. In view of the lower rate of lymph node metastasis and better
      prognosis, we suggest that EMR can be performed on patients with early SRC
      limited to the mucosa, less than 2cm in size, and with no lymphatic involvement.

PMID- 18071826
TI  - Secondary analyses of large population-based data sets: issues of quality,
      standards, and understanding.

PMID- 18071827
TI  - Two-fluid model of biofilm disinfection.
AB  - We consider a dynamic model of biofilm disinfection in two dimensions. The
      biofilm is treated as a viscous fluid immersed in a fluid of less viscosity. The
      bulk fluid moves due to an imposed external parabolic flow. The motion of the
      fluid is coupled to the biofilm inducing motion of the biofilm. Both the biofilm
      and the bulk fluid are dominated by viscous forces, hence the Reynolds number is
      negligible and the appropriate equations are Stokes equations. The governing
      partial differential equations are recast as boundary integral equations using a
      version of the Lorenz reciprocal relationship. This allows for robust treatment
      of the simplified fluid/biofilm motion. The transport of nutrients and
      antimicrobials, which depends directly on the velocities of the fluid and
      biofilm, is also included. Disinfection of the bacteria is considered under the
      assumption that the biofilm growth is overwhelmed by disinfection.

PMID- 18071828
TI  - Klebsiella pneumoniae flocculation dynamics.
AB  - The bacterial pathogen Klebsiella pneumoniae is a cause of community- and
      hospital-acquired lung, urinary tract and blood stream infections. It is a common
      contaminant of indwelling catheters and it is theorized in that context that
      systemic infection follows shedding of aggregates off of surface-adherent biofilm
      colonies. In an effort to better understand bacterial proliferation in the host
      bloodstream, we develop a PDE model for the flocculation dynamics of Klebsiella
      pneumoniae in suspension. Existence and uniqueness results are provided, as well
      as a brief description of the numerical approximation scheme. We generate
      artificial data and illustrate the requirements to accurately identify
      proliferation, aggregation, and fragmentation of flocs in the experimental domain
      of interest.

PMID- 18071829
TI  - Community and family perspectives on addressing overweight in urban, African
      American youth.
AB  - OBJECTIVE: To assess weight-related beliefs and concerns of overweight urban,
      African-American children, their parents, and community leaders before developing
      a family-based intervention to reduce childhood overweight and diabetes risk.
      DESIGN: We conducted 13 focus groups with overweight children and their parents
      and eight semistructured interviews with community leaders. PARTICIPANTS AND
      SETTING: Focus group participants (N = 67) from Chicago's South Side were
      recruited through flyers in community sites. Interview participants (N = 9) were
      recruited to sample perspectives from health, fitness, education, civics, and
      faith leaders. RESULTS: Community leaders felt awareness was higher for acute
      health conditions than for obesity. Parents were concerned about their children's
      health, but felt stressed by competing priorities and constrained by lack of
      knowledge, parenting skills, time, and financial resources. Parents defined
      overweight in functional terms, whereas children relied upon physical
      appearances. Children perceived negative social consequences of overweight.
      Parents and children expressed interest in family-based interventions to improve
      nutrition and physical activity and offered suggestions for making programs
      interesting. CONCLUSIONS: This study provides insights into the perspectives of
      urban, African-American overweight children, their parents, and community leaders
      regarding nutrition and physical activity. The specific beliefs of these
      respondents can become potential leverage points in interventions.

PMID- 18071830
TI  - Use of antireflux medication after antireflux surgery.
AB  - INTRODUCTION: It is claimed that a substantial number of patients who undergo
      antireflux surgery use antireflux medication postoperatively. This study was
      aimed to determine the prevalence and underlying reasons for antireflux
      medication usage in patients after surgery. MATERIALS AND METHODS: A
      questionnaire on the usage of antireflux medication was sent to 1,008 patients
      identified from a prospective database of patients who had undergone a
      laparoscopic antireflux procedure. RESULTS: A total of 844 patients (84%)
      returned the questionnaire. Mean follow-up was 5.9 years after surgery. A single
      or combination of medications was being taken by 312 patients (37%): 82% proton
      pump inhibitors, 9% H2-blockers and 34% antacids. Fifty-two patients (17%) had
      never stopped taking medication, whereas 260 patients (83%) restarted medication
      at a mean of 2.5 years after surgery. Return of the same (31%) or different (49%)
      symptoms were the commonest reasons for taking medication, whereas 20% were
      asymptomatic or had other reasons for medication use. Postoperative 24-hour pH
      studies were abnormal in 16/61 patients (26%) on medication and in 5/78 patients
      (6%) not taking medication. CONCLUSIONS: Antireflux medication is frequently
      taken by many patients for various symptoms after antireflux surgery. Symptomatic
      patients should be properly investigated before antireflux medications are
      prescribed.

PMID- 18071831
TI  - Catastrophic Clostridium difficile enteritis in a pelvic pouch patient: report of
      a case.
AB  - INTRODUCTION: In recent years, Clostridium difficile-associated infection has
      emerged as an increasingly problematic entity. More virulent strains have been
      isolated and new manifestations of the infection have been described. PURPOSE:
      The primary aim of this manuscript is to describe what we believe to be the first
      reported case of devastating C. difficile enteritis in a patient with an ileal
      reservoir. CONCLUSION: A high index of suspicion is required in the appropriate
      clinical setting in light of the apparently changing spectrum of C. difficile
      disease.

PMID- 18071832
TI  - A comprehensive appraisal of the surgical treatment of diffuse esophageal spasm.
AB  - Diffuse esophageal spasm is a motility disorder of undetermined cause. The
      optimal treatment remains controversial, and evidence-based data are lacking.
      Several medical treatment modalities have been proposed, but none has emerged as
      the treatment of choice. Patients who do not respond to medical therapy may be
      considered for surgical treatment. The surgical treatment of diffuse esophageal
      spasm is based on similar principles to the treatment of achalasia. A long
      esophageal myotomy is done to divide the hypertrophied circular muscle that is
      frequently noted in diffuse esophageal spasm. To protect against postoperative
      reflux, an antireflux procedure may be added. However, the surgical treatment of
      diffuse esophageal spasm has not been subjected to randomized clinical trials.
      The purpose of this article is to provide a review of the available literature
      regarding the surgical management of the diffuse esophageal spasm. In particular,
      we offer an appraisal of surgical outcomes, the effects of surgery on manometric
      and radiologic parameters (when available), complications, and mortality.

PMID- 18071833
TI  - Comparison of stapled versus handsewn loop ileostomy closure: a meta-analysis.
AB  - The purpose of this study was to compare the rates of small bowel obstruction,
      anastomotic complications, and wound infections between stapled and handsewn
      closures of loop ileostomies. A literature search in Embase, PubMed, and Cochrane
      Database for Clinical Trials using search terms "closure," "loop ileostomy," and
      "stapled" was performed. All abstracts were reviewed to identify relevant
      articles, and their references were hand searched for additional studies. Six
      articles were identified for inclusion. Three independent reviewers extracted the
      following data: rates of small bowel obstruction, anastomotic complications,
      wound infection; length of hospital stay; and operative time. Data analysis was
      performed using Stata statistical software. Comparing stapled versus hand-sewn
      closures, there were no statistically significant differences in bowel
      obstruction (relative risk [RR] 0.69, 95% confidence interval [CI] 0.44 to 1.09),
      wound infection (RR 0.91, 95% CI 0.53 to 1.97), or anastomotic complication rates
      (RR 1.01, 95% CI 0.99 to 1.03). Two studies showed shorter operative times
      favoring stapled anastomoses. No difference was seen in length of stay. Current
      literature suggests no statistically significant differences between stapled and
      hand-sewn loop ileostomy closures, but there may be a trend favoring stapled
      closures with regard to lower small bowel obstruction rates and shorter operative
      time.

PMID- 18071834
TI  - Letter to the editors.

PMID- 18071835
TI  - A case of peribiliary cyst presenting with obstructive jaundice.
AB  - A 77-year-old woman with a complaint of itching was shown to have an elevated
      serum bilirubin level. She had no history of liver disease. Computed tomography
      and magnetic resonance cholangiopancreatography revealed a 17-mm-diameter cystic
      lesion obstructing the main hepatic duct at the hepatic hilum. Drip infusion
      cholangiographic computed tomography and endoscopic retrograde cholangiography
      showed that the cyst did not communicate with the biliary tree; thus, a
      peribiliary cyst was diagnosed. Cystectomy was performed, and the jaundice
      resolved. Peribiliary cysts are generally asymptomatic and rarely cause
      obstructive jaundice. They are usually multiple and caused by an underlying liver
      disorder with a poor prognosis. Our case suggests that peribiliary cysts can
      arise in healthy liver and cause symptoms. Cystectomy is the treatment of choice
      if the cyst is solitary.

PMID- 18071836
TI  - Suboptimal weight loss after gastric bypass surgery: correlation of demographics,
      comorbidities, and insurance status with outcomes.
AB  - Although Roux-en-Y gastric bypass surgery (RYGBP) is safe and effective at
      achieving weight loss in the majority of severely obese patients, a subset fails
      to achieve expected weight loss outcomes. Factors associated with poor weight
      loss are not well defined. Patients undergoing open RYGBP using a standardized
      surgical technique and clinical pathway by a single surgeon at a dedicated
      bariatric center were reviewed. Suboptimal weight loss was defined as failure to
      lose at least 40% excess body weight by 12 months postoperatively. Of 555
      consecutive patients who underwent RYGBP from 1999 to 2004, a 12-month follow-up
      was available for the 495 (89%). Suboptimal weight loss occurred in 55 (11%) and
      was associated on unadjusted bivariate analysis with increased body mass index
      (BMI; p = 0.0002), diabetes mellitus (p = 0.0002), Medicaid insurance (p = 0.04),
      and male sex (p = 0.01). On adjusted multivariate analysis, increased BMI (p =
      0.003), diabetes (p = 0.002), and male gender (p = 0.04) were associated with
      suboptimal weight loss, but type of insurance (p = 0.11) was not. Medicaid
      patients were younger (p = 0.01) and had higher BMI (p = 0.0002). Suboptimal
      weight loss after RYGBP appears to be associated with greater BMI, male sex, and
      diabetes but not type of insurance. This study may help identify patients who
      could benefit from increased perioperative education and counseling or selection
      of procedures with greater malabsorption.

PMID- 18071837
TI  - Mutational analysis of thyroid transcription factor-1 gene (TTF-1) in lung
      carcinomas.
AB  - We studied the expression and mutation of thyroid transcription factor-1 (TTF-1)
      gene in 92 cases of lung carcinomas comprised of lung adenocarcinoma (36 cases),
      squamous cell lung carcinoma (42 cases), small cell lung carcinoma (8 cases), and
      large cell lung carcinoma (6 cases) to investigate whether TTF-1 gene mutation
      predisposed to the development of lung cancer. Normal lung tissues were obtained
      from each of the 92 patients. The tissues served as controls. Polymerase chain
      reaction-single-strand conformation polymorphism, denaturing high-performance
      liquid chromatography, and DNA sequencing were used to analyze TTF-1 gene
      mutation and its relationship with the carcinogenesis of lung cancer. We detected
      the expression of TTF-1 protein and messenger RNA (mRNA) in paraffin-embedded
      lung carcinomas and their normal lung tissues by tissue microarray. TTF-1 protein
      and mRNA intensities were measured by Leica-Q500 MC Image Analysis System to
      reveal their correlation with TTF-1 mutation in lung carcinomas. TTF-1 gene
      missense and synonymous mutation are present in lung carcinomas with the mutation
      rate of 16%. TTF-1 protein and mRNA are higher in normal lung tissues than in
      different lung carcinomas. TTF-1 gene mutation is correlated with the loss of TTF
      1 protein and mRNA. The analyses of TTF-1 gene missense mutation and synonymous
      mutation and the loss of TTF-1 protein and mRNA can be regarded as the important
      indexes of molecular pathology of lung carcinoma.

PMID- 18071839
TI  - Prevention of parastomal hernias by prophylactic use of a specially designed
      intraperitoneal onlay mesh (Dynamesh IPST).
AB  - BACKGROUND: Hernias around ostomies are a very common complication, exceeding
      50%. Only a few studies deal with the prophylactic use of mesh to prevent
      parastomal hernia revealing promising results. PATIENTS AND METHODS: Twenty-two
      patients undergoing elective rectal surgery with a permanent colostomy--one with
      an ileostomy and two needing surgical correction of a preexisting colostomy--were
      enrolled in a prospective study. A specially designed mesh made of polyvinylidene
      fluoride with a central whole and a funnel arising (Dynamesh IPST) was
      prophylactically implanted using an intraperitoneal onlay technique. The patients
      were followed for a median of 11 (range 2-19) months by clinical examination
      every 3 months. RESULTS: No infection or any other adverse effect was observed,
      and no parastomal hernia or stoma protrusion could be detected clinically. Twelve
      patients had a routine computed tomography after 6 months, which also excluded
      any hernia formation. CONCLUSION: The prophylactic use of Dynamesh IPST) is a
      safe and effective procedure preventing stoma complications such as hernia
      formation or prolapse, at least in the short run.

PMID- 18071840
TI  - Heterogeneity in the pharmacodynamics of two long-acting methylphenidate
      formulations for children with attention deficit/hyperactivity disorder. A growth
      mixture modelling analysis.
AB  - OBJECTIVES: To use growth mixture modelling (GMM) to identify subgroups of
      children with attention deficit hyperactive disorder (ADHD) who have different
      pharmacodynamic profiles in response to extended release methylphenidate as
      assessed in a laboratory classroom setting. METHODS: GMM analysis was performed
      on data from the COMACS study (Comparison of Methylphenidates in the Analog
      Classroom Setting): a large (n = 184) placebo-controlled cross-over study
      comparing three treatment conditions in the Laboratory School Protocol (with a
      1.5-h cycle of attention and deportment assessments). Two orally administered,
      once-daily methylphenidate (MPH) bioequivalent formulations [Metadate CD/Equasym
      XL (MCD-EQXL) and Concerta XL (CON)] were compared with placebo (PLA). RESULTS:
      Three classes of children with distinct severity profiles in the PLA condition
      were identified. For both MCD-EQXL and CON, the more severe their PLA symptoms
      the better, the children's response. However, the formulations produced different
      growth curves by class, with CON having essentially a flat profile for all three
      classes (i.e. no effect of PLA severity) and MCD-EQXL showing a marked decline in
      symptoms immediately post-dosing in the two most severe classes compared with the
      least severe. Comparison of daily doses matched for immediate-release (IR)
      components accounted for this difference. CONCLUSION: The results suggest
      considerable heterogeneity in the pharmacodynamics of MPH response by children
      with ADHD. When treatment response for near-equal, bioequivalent daily doses the
      two formulations was compared, marked differences were seen for children in the
      most severe classes with a strong curvilinear trajectory for MCD-EQXL related to
      the greater IR component.

PMID- 18071841
TI  - The FRIENDS emotional health prevention programme: 12 month follow-up of a
      universal UK school based trial.
AB  - A universal cognitive behaviour therapy emotional health programme, FRIENDS, was
      provided in schools by trained school nurses to 106 children aged 9/10. Anxiety
      and self-esteem were re-assessed in 63 children one year after completing the
      programme. The significant improvements in emotional health identified 3 months
      after FRIENDS were maintained 12 month after completing the programme. Of the 9
      children identified at baseline as high risk, 6 (67%) had moved into the low risk
      category by the 12 month follow-up. Of the low risk children, none had become
      high risk by follow-up. The study conclusions are limited by a small sample size
      and the absence of a comparison group. They are however consistent with previous
      studies and suggest that FRIENDS delivered in schools as a universal intervention
      can have a significant medium term effect upon emotional health.

PMID- 18071842
TI  - Application of the Phenomenex EZ:faasttrade mark amino acid analysis kit for
      rapid gas-chromatographic determination of concentrations of plasma tryptophan
      and its brain uptake competitors.
AB  - The Phenomenex EZ:faast amino acid analysis kit is available for gas (GC) or
      liquid (LC) chromatographic analysis of amino acids (AA) using mass spectrometry
      (MS) and other GC detectors. We used it for rapid GC determination of plasma
      tryptophan, its brain uptake competitors (Val, Leu, Ile, Phe and Tyr) and many
      other amino acids. Based on solid-phase extraction, this fast method enables one
      person to process two plasma samples in 8-10 min and six samples in approximately
      15 min up to GC injection and a 7-min GC run per plasma sample. Using a Perkin
      Elmer Clarus 500 GC, a Total Chrome software, a flame-ionisation detector (FID)
      and norvaline as internal standard, we used this method to analyse approximately
      1,000 plasma samples from normal subjects undergoing acute tryptophan depletion
      and loading tests. The limit of detection for most amino acids is 1 nmol/ml (1
      microM) and in many cases less. With manual injection, coefficients of variation
      for the above six amino acids were 1.5-6.2% (intra-assay) and 3.8-9.7% (inter
      assay). This simple, rapid and elegant method will be valuable to the amino acid
      analyst and researcher, as it can save much manpower time and meet urgent
      emergency requests and the demands of a high-throughput laboratory.

PMID- 18071843
TI  - Hydrogen sulfide inhibits myocardial injury induced by homocysteine in rats.
AB  - Hyperhomocysteinemia (HHcy) is a critical independent risk factor for
      cardiovascular diseases. However, to date, no satisfactory strategies to prevent
      HHcy exist. Since homocysteine (Hcy) and endogenous H2S are both metabolites of
      sulfur-containing amino acids, we aimed to investigate whether a metabolic
      product of Hcy and H2S, may antagonize in part the cardiovascular effects of Hcy.
      In the HHcy rat model injected subcutaneously with Hcy for 3 weeks, H2S levels
      and the H2S-generating enzyme cystathionine gamma lyase (CSE) activity in the
      myocardium were decreased. The intraperitoneal injection of H2S gas saturation
      solution significantly reduced plasma total Hcy (tHcy) concentration and
      decreased lipid peroxidation formation (i.e., lowered manodialdehyde and
      conjugated diene levels in myocardia and plasma). The activities of myocardial
      mitochondrial respiratory enzymes succinate dehydrogenase, cytochrome oxidase,
      and manganese superoxide dismutase, related to reactive oxygen species
      metabolism, were significantly dysfunctional in HHcy rats. The H2S administration
      restored the level of enzyme activities and accelerated the scavenging of H2O2
      and superoxide anion generated by Hcy in isolated mitochondria. The H2S treatment
      also inhibited the expression of glucose-regulated protein 78, a marker of
      endoplasmic reticulum (ER) stress, induced by Hcy in vivo and in vitro. Thus,
      HHcy impaired the myocardial CSE/H2S pathway, and the administration of H2S
      protected the myocardium from oxidative and ER stress induced by HHcy, which
      suggests that an endogenous metabolic balance of sulfur-containing amino acids
      may be a novel strategy for treatment of HHcy.

PMID- 18071845
TI  - Effectiveness of phenoxyl radicals generated by peroxidase/H2O2-catalyzed
      oxidation of caffeate, ferulate, and p-coumarate in cooxidation of ascorbate and
      NADH.
AB  - The rate of ascorbate and nicotinamide adenine dinucleotide plus hydrogen (NADH)
      cooxidation (i.e., their nonenzymic oxidation by peroxidase/H2O2-generated
      phenoxyl radicals of three hydroxycinnamates: caffeate, ferulate and p-coumarate)
      was studied in vitro. The reactions initiated by different sources of peroxidase
      (EC 1.11.1.7) [isolates from soybean (Glycine max L.) seed coat, maize (Zea mays
      L.) root-cell wall, and commercial horseradish peroxidase] were monitored. Native
      electrophoresis of samples and specific staining for peroxidase activity revealed
      various isoforms in each of the three enzyme sources. The peroxidase sources
      differed both in the rate of H2O2-dependent hydroxycinnamate oxidation and in the
      order of affinity for the phenolic substrates. The three hydroxycinnamates did
      not differ in their ability to cooxidize ascorbate, whereas NADH cooxidation was
      affected by substitution of the phenolic ring. Thus, p-coumarate was more
      efficient than caffeate in NADH cooxidation, with ferulate not being effective at
      all. Metal ions (Zn2+ and Al3+) inhibited the reaction of peroxidase with p
      coumarate and affected the cooxidation rate of ascorbate and the peroxidase
      reaction in the same manner with all substrates used. However, inhibition of p
      coumarate oxidation by metal ions did not affect NADH cooxidation rate. We
      propose that both the ascorbate and NADH cooxidation systems can function as
      mechanisms to scavenge H2O2 and regenerate phenolics in different cellular
      compartments, thus contributing to protection from oxidative damage.

PMID- 18071846
TI  - Domestic and foreign trends in the prevalence of heart failure and the necessity
      of next-generation artificial hearts: a survey by the Working Group on
      Establishment of Assessment Guidelines for Next-Generation Artificial Heart
      Systems.
AB  - A series of guidelines for development and assessment of next-generation medical
      devices has been drafted under an interagency collaborative project by the
      Ministry of Health, Labor and Welfare and the Ministry of Economy, Trade and
      Industry. The working group for assessment guidelines of next-generation
      artificial hearts reviewed the trend in the prevalence of heart failure and
      examined the potential usefulness of such devices in Japan and in other countries
      as a fundamental part of the process of establishing appropriate guidelines. At
      present, more than 23 million people suffer from heart failure in developed
      countries, including Japan. Although Japan currently has the lowest mortality
      from heart failure among those countries, the number of patients is gradually
      increasing as our lifestyle becomes more Westernized; the associated medical
      expenses are rapidly growing. The number of heart transplantations, however, is
      limited due to the overwhelming shortage of donor hearts, not only in Japan but
      worldwide. Meanwhile, clinical studies and surveys have revealed that the major
      causes of death in patients undergoing long-term use of ventricular assist
      devices (VADs) were infection, thrombosis, and mechanical failure, all of which
      are typical of VADs. It is therefore of urgent and universal necessity to develop
      next-generation artificial hearts that have excellent durability to provide at
      least 2 years of event-free operation with a superior quality of life and that
      can be used for destination therapy to save patients with irreversible heart
      failure. It is also very important to ensure that an environment that facilitates
      the development, testing, and approval evaluation processes of next-generation
      artificial hearts be established as soon as possible.

PMID- 18071847
TI  - Circulatory assistance in small infants and neonates with a hydraulically driven
      system: a viable option?
AB  - We have developed a new drive system for a cardiac assist system for use with
      newborns and infants. This study reports results of animal experiments in which
      this system was tested using a commercially available 25-ml ventricle. A major
      property of the device is its hydraulic mode, which allows not only for the
      conventional full-empty mode (chamber completely filled in diastole) but also for
      the filled-empty mode, in which the chamber is completely emptied in systole but
      only partially filled in systole; this mode gives full flexibility to adjust the
      pump frequency for any given pump flow rate. The assist device was applied in
      eight pigs (weight 9-14 kg) for left ventricular assistance during normal and
      impaired cardiac function (pacing-induced cardiac shock, mean arterial blood
      pressure less than 40 mmHg). Both, full-empty and filled-empty mode during normal
      cardiac function led to significantly decreased pulmonary capillary wedge
      pressure, suggesting load reduction of the right ventricle. In impaired cardiac
      function, circulatory assistance increased the diminished cardiac output and
      systolic arterial blood pressure, although only the latter was statistically
      significant. Neither arterial lactate concentration nor oxygen uptake was reduced
      during circulatory assistance for normal and impaired cardiac function. These
      results suggest that the cardiac ventricular assist device can be used as an
      effective circulatory assist device and that the function of the newly introduced
      filled-empty mode, which allows for a high degree of functional flexibility, is
      not inferior to that of the classical, but less flexible, full-empty mode.

PMID- 18071848
TI  - Development of an educational simulator system, ECCSIM-Lite, for the acquisition
      of basic perfusion techniques and evaluation.
AB  - A training system with quantitative evaluation of performance for training
      perfusionists is valuable for preparation for rare but critical situations. A
      simulator system, ECCSIM-Lite, for extracorporeal circulation (ECC) training of
      perfusionists was developed. This system consists of a computer system containing
      a simulation program of the hemodynamic conditions and the training scenario with
      instructions, a flow sensor unit, a reservoir with a built-in water level sensor,
      and an ECC circuit with a soft bag representing the human body. This system is
      relatively simple, easy to handle, compact, and reasonably inexpensive.
      Quantitative information is recorded, including the changes in arterial flow by
      the manipulation of a knob, the changes in venous drainage by handling a clamp,
      and the change in reservoir level; the time courses of the above parameters are
      presented graphically. To increase the realism of the training, a numerical
      hydraulic circulatory model was applied. Following the instruction and
      explanation of the scenario in the form of audio and video captions, it is
      possible for a trainee to undertake self-study without an instructor or a
      computer operator. To validate the system, a training session was given to three
      beginners using a simple training scenario; it was possible to record the
      performance of the perfusion sessions quantitatively. In conclusion, the ECCSIM
      Lite system is expected to be useful for perfusion training, since quantitative
      information about the trainee's performance is recorded and it is possible to use
      the data for assessment and comparison.

PMID- 18071849
TI  - Patient-prosthesis mismatch may be irrelevant after aortic valve replacement with
      the 19-mm Perimount pericardial bioprosthesis in patients aged 65 years or older.
AB  - The prevalence of patient-prosthesis mismatch (PPM) and its influence on clinical
      midterm results were examined in elderly patients whose activity was supposed to
      be less than that of younger patients. We evaluated valve function and the
      effects of PPM on the midterm results of the 19-mm Carpentier-Edwards Perimount
      (CEP) pericardial aortic valve in patients aged 65 years or older. Between August
      1996 and May 2005, 51 patients underwent aortic valve replacement with the 19-mm
      CEP valve. The mean follow-up was 2.4 +/- 1.8 years, involving a total of 134.4
      patient-years. The mean age and body surface area at operation were 74.0 +/- 5.0
      years and 1.41 +/- 0.14 m(2). There were two (3.9%) operative deaths. Three
      patients (5.9%) underwent enlargement of their small aortic annuli. The actuarial
      survival rate at 8 years, including operative mortality, averaged 90.2% +/- 4.7%.
      The freedom from thromboembolism, reoperation, and valve-related mortality
      averaged 75.0% +/- 21.7%, 97.8% +/- 2.2%, and 95.3% +/- 3.2%, respectively, at 8
      years. High preoperative peak and mean transvalvular pressure gradients were
      significantly improved after the operation (peak, 93 +/- 35 versus 28 +/- 12
      mmHg; mean, 58 +/- 19 versus 17 +/- 7 mmHg, respectively; P < 0.01). The mean
      left ventricular mass index was reduced from 192 +/- 44 to 142 +/- 46 g/m(2) at
      late follow-up (P < 0.01). The prevalence of PPM was low (17.6%) when an indexed
      effective orifice area of less than 0.85 cm(2)/m(2) was taken as the definition
      of PPM. The clinical results, postoperative pressure gradients, and reduction in
      left ventricular mass index were not different between the PPM and no-PPM groups.
      The 19-mm CEP valve produced satisfactory midterm clinical outcomes in patients
      aged 65 years or older whose activity was supposed to be less than that of
      younger patients, regardless of the presence or absence of PPM. Moderate PPM was
      rare and it did not adversely impact on the midterm results. The application of
      annulus enlargement could be limited to the small number of patients for whom the
      19-mm CEP valves are not able to be inserted.

PMID- 18071850
TI  - Acceleration of bone formation with BMP2 in frame-reinforced carbonate apatite
      collagen sponge scaffolds.
AB  - The development is expected of scaffold biomaterials that feature a shape
      maintaining property in addition to high porosity and large pores that cells can
      easily invade. To develop a new biodegradable scaffold biomaterial reinforced
      with a frame, synthesized carbonate apatite (CO3Ap) was mixed with neutralized
      collagen gel, and the CO3Ap-collagen mixtures were lyophilized into sponges in a
      porous hydroxyapatite (HAp) frame ring. X-ray diffraction and Fourier transform
      infrared spectroscopy (FT-IR) analyses together with chemical analysis indicated
      that the synthesized CO3Ap had a crystalline nature and a chemical composition
      similar to that of bone. Scanning electron microscope (SEM) observation showed
      that the CO3Ap-collagen sponge had a sui pore size for cell invasion. In
      proliferation and differentiation experiments with osteoblasts, alkaline
      phosphatase and osteopontin activity were clearly detected. When these sponge
      frame complexes with bone morphogenic protein (rh-BMP2) were implanted beneath
      the periosteum cranii of rats, significant new bone was created at the surface of
      the periosteum cranii after 4 weeks of implantation. These reinforced CO3Ap
      collagen sponges with rh-BMP2 are expected to be used as hard tissue scaffold
      biomaterials for the therapeutic purpose of the rapid cure of bone defects.

PMID- 18071851
TI  - Clinical experience with Smart Care after off-pump coronary artery bypass for
      early extubation.
AB  - The purpose of this study was to compare the intubation time using Smart Care, a
      knowledge-based system for automated weaning, with that of conventional physician
      controlled weaning after off-pump coronary artery bypass (OPCAB) and to determine
      the efficacy of Smart Care. During 2004, 53 sequential patients were scheduled
      for isolated coronary artery bypass grafting without cardiopulmonary bypass.
      Patients were divided into two groups: the Smart Care group (n = 10) and the
      control group (n = 35). Eight patients requiring hemodialysis and patients
      undergoing the awake OPCAB method were excluded. The intubation times were 172.6
      +/- 51.6 min in the Smart Care group compared with 342.0 +/- 239.0 min in the
      control group (P = 0.032). No specific complications occurred with this computer
      driven expert weaning system. In conclusion, the Smart Care system reduced the
      duration of mechanical ventilation and the respiratory care workload. This system
      was effective in the care of patients without complications requiring mechanical
      ventilation after OPCAB.

PMID- 18071852
TI  - Biochemical evaluation of an artificial anal sphincter made from shape memory
      alloys.
AB  - Severe anal incontinence is a socially incapacitating disorder and a major
      unresolved clinical problem that has a considerable negative impact on quality of
      life. In this study, we developed a new artificial anal sphincter using shape
      memory alloys (SMAs) in order to improve the quality of life of such patients and
      evaluated the influence of this sphincter on blood serum chemistry in animal
      experiments. The artificial anal sphincter was driven by two Ti-Ni SMA actuators
      sandwiching the intestine and was implanted in three female goats. Blood was
      collected from the jugular vein on days 1 and 4; at weeks 1 and 2; and at months
      1, 2, and 3, postoperatively. Biochemical parameters including total protein,
      albumin, total bilirubin, aspartate amino-transferase, blood urea nitrogen,
      creatinine, and C-reactive protein were examined. The time courses of total
      bilirubin and aspartate amino transferase of the three goats were within the
      baseline levels after 1 week of implantation and remained normal, demonstrating
      no liver function complications. The blood urea nitrogen and creatinine levels
      remained within the normal range, indicating no renal function complications. The
      total protein and albumin fluctuated within the normal range throughout the
      duration of this study. In these goats, it was also found that the level of C
      reactive protein did not increase and that there was no stricture of the
      intestine where the artificial sphincter was attached. Our findings indicate that
      the artificial sphincter SMA demonstrated no adverse influence on blood serum
      chemistry and exhibited an effective system performance.

PMID- 18071853
TI  - Simple method of left ventricular assist system exchange from a BVS-5000 to a
      Toyobo: case report of a patient with fulminant myocarditis.
AB  - We implanted a BVS-5000 biventricular assist system in a 29-year-old woman in
      cardiogenic shock due to fulminant myocarditis. Exchange of the left ventricular
      assist system (LVAS) from the BVS-5000 to a Toyobo LVAS and weaning from the
      right ventricular assist system were performed successfully without
      cardiopulmonary bypass. This simple, less invasive method may be useful for
      patients requiring LVAS exchange for long-term ventricular support.

PMID- 18071854
TI  - Fundamental study to develop a fiber-optic gap sensor for a rotary undulation
      pump.
AB  - The rotary undulation pump is believed to be a good candidate for the next
      generation artificial heart. Due to its complex movement, it is desirable to
      magnetically levitate the rotor and dynamically control the gap. In this article,
      the applicability of a fiber-optic gap sensor to the dynamic position control of
      the rotor in the rotary undulation pump was investigated. The fiber-optic gap
      sensor consisted of two plastic-core fibers and a reflection plate. Two 1-mm
      diameter optical fibers were aligned parallel: one for source light propagation
      and the other for reflected light transmission. The basic properties of gap
      sensors using four different light sources were explored in five media (air,
      physiologic saline, and blood samples with three different hematocrit levels).
      The influence of the oxygen saturation level in the blood on sensing was
      investigated with two types of light sources. It is desirable to use a light
      source the wavelength of which shows similar absorption coefficients for both
      oxygenated blood and deoxygenated blood. The effect of the distance between the
      two fibers on the sensing and range was also investigated. The results indicated
      that the fiber-optic gap sensor is quite promising for the active control of
      rotor positioning in the rotary undulation pump.

PMID- 18071855
TI  - Development of a compact portable driver for a pneumatic ventricular assist
      device.
AB  - The Toyobo-National Cardiovascular Center pneumatic ventricular assist device
      (Toyobo-NCVC VAD) is widely used in Japan; however, the current pneumatic drivers
      have some drawbacks, including their large size, heavy weight, and high power
      consumption. These issues cause difficulty with mobility and contribute to an
      unsatisfactory quality of life for patients. Because it is urgently necessary to
      improve patients' safety and quality of life, we have developed a compact, low
      noise, portable VAD driver by utilizing an electrohydraulic actuator consisting
      of a brushless DC motor and a regenerative pump. This unit can be actuated for as
      long as 2 h with two rechargeable lightweight batteries as well as with external
      AC power. It is compact in size (33 x 25 x 43 cm) and light in weight (13 kg),
      and the unit is carried on a mobile wheeled cart. In vitro testing with a Toyobo
      NCVC VAD demonstrated a sufficient pumping capacity of up to 8 l/min. We conclude
      that this newly-developed compact portable driver can provide a better quality of
      life and improved safety for patients using protracted pneumatic VAD support.

PMID- 18071856
TI  - Up to 151 days of continuous animal perfusion with trivial heparin infusion by
      the application of a long-term durable antithrombogenic coating to a combination
      of a seal-less centrifugal pump and a diffusion membrane oxygenator.
AB  - We developed a new coating material (Toyobo-National Cardiovascular Center
      coating) for medical devices that delivers high antithrombogenicity and long-term
      durability. We applied this coating to an extracorporeal membrane oxygenation
      (ECMO) system, including the circuit tube, cannulae, a seal-less centrifugal
      pump, and a diffusion membrane oxygenator, to realize prolonged cardiopulmonary
      support with trivial anticoagulant infusion. The oxygenator consisted of a hollow
      fiber membrane made of polymethylpentene, which allows the transfer of gas by
      diffusion through the membrane. The centrifugal pump was free of seals and had a
      pivot bearing. We performed a venoarterial bypass in a goat using this ECMO
      system, and the system was driven for 151 days with trivial anticoagulant
      infusion. Plasma leakage from the oxygenator did not occur and sufficient gas
      exchange performance was well maintained. In the oxygenator, thrombus formation
      was present around the top and the distributor of the inlet portion and was very
      slight in the outlet portion. In the centrifugal blood pump, there was some wear
      in the female pivot region and quite small amounts of thrombus formation on the
      edge of the shroud; the pivot wear seemed to be the cause of the hemolysis
      observed after 20 weeks of perfusion and which resulted in the termination of the
      perfusion. However, no significant amounts of thrombus were observed in other
      parts of the system. This ECMO system showed potential for long-term
      cardiopulmonary support with minimal use of systemic anticoagulants.

PMID- 18071857
TI  - Recent advances in nonsurgical management of localized prostate cancer.

PMID- 18071858
TI  - Brachytherapy with permanent seed implantation.
AB  - Permanent interstitial brachytherapy with iodine-125 (I-125) or palladium 103 (Pd
      103) seeds is a common treatment option in the United States, and numerous
      articles on outcomes after long-term follow up have been published. With the
      treatment's apparent high efficacy and low morbidity, permanent seed implantation
      has become the most frequently employed procedure for localized prostate cancer
      and has replaced radical prostatectomy. Even taking into account the good
      features of the treatment, the performance of permanent seed implantation in
      Japan had not been allowed because of the country's strict laws on radiation
      safety. However, after a long period of discussion between Japanese medical
      associations and the government, permanent interstitial brachytherapy with I-125
      was finally approved in Japan in July 2003. The guidelines for this treatment
      include several restrictions that should be followed by each institution that is
      to perform the treatment. Over 70 institutes around the country had started the
      treatment before the end of June 2007. With high expectations for this new
      radiation therapy, which may be effective, and less invasive than previous
      treatments and with a low incidence of treatment morbidity, brachytherapy for
      prostate cancer will become more common in Japan. For the purpose of improving
      the quality of seed implantation, which may lead to better clinical outcomes and
      radiation safety, medical conferences and technical training courses have been
      carried out regularly, and multi-institutional clinical studies have also been
      carried out countrywide.

PMID- 18071859
TI  - Current status of intensity-modulated radiation therapy (IMRT).
AB  - External-beam radiation therapy has been one of the treatment options for
      prostate cancer. The dose response has been observed for a dose range of 64.8-81
      Gy. The problem of external-beam RT for prostate cancer is that as the dose
      increases, adverse effects also increase. Three-dimensional conformal radiation
      therapy (3D-CRT) has enabled us to treat patients with up to 72-76 Gy to the
      prostate, with a relatively acceptable risk of late rectal bleeding. Recently,
      intensity-modulated radiation therapy (IMRT) has been shown to deliver a higher
      dose to the target with acceptable low rates of rectal and bladder complications.
      The most important things to keep in mind when using an IMRT technique are that
      there is a significant trade-off between coverage of the target, avoidance of
      adjacent critical structures, and the inhomogeneity of the dose within the
      target. Lastly, even with IMRT, it should be kept in mind that a "perfect" plan
      that creates completely homogeneous coverage of the target volume and zero or
      small dose to the adjacent organs at risk is not always obtained. Participating
      in many treatment planning sessions and arranging the beams and beam weights
      create the best approach to the best IMRT plan.

PMID- 18071860
TI  - Cryotherapy.

PMID- 18071861
TI  - Hormonal therapy.
AB  - In spite of clinical practice guidelines such as the National Cancer Institute
      (NCI)-Physician Data Query (PDQ), in which primary androgen deprivation therapy
      (PADT) is not recommended at all as the primary treatment for localized prostate
      cancer, many such patients have actually been treated with PADT in Japan. The
      reasons are probably that medical treatment such as PADT is more acceptable than
      more invasive treatments such as surgery for many Japanese patients, and that
      urologists themselves have also conform to their patient's wishes for the
      treatment, because they know the effectiveness of PADT in their experiences. In
      this review, we note clinical trials in which the efficacy of PADT for localized
      or locally advanced prostate cancer is demonstrated. Then, we discuss which
      patients are candidates for PADT, and show that more than 30% of low- or
      intermediate-risk localized prostate cancer can be controlled long term with
      PADT. Although the duration of PADT is also discussed, short-term or intermittent
      PADT cannot be recommended, because cancer cells which can be controlled for a
      long-term period or cancer that may appear to be cured by appropriate PADT may
      progress to cancer cells with more malignant potential with incomplete androgen
      ablation. We propose algorithms for the treatment of localized prostate cancer
      not only in low- and intermediate-risk groups but also in the high-risk group.
      Although the side effects of PADT affecting the healthy status of prostate cancer
      patients may not be serious, as reported in several studies, adverse effects
      caused by ADT on physical and mental conditions, such as osteoporosis and anemia,
      should be overcome by adequate treatment. Ideally, new hormonal compounds
      targeted only for prostate cancer will be developed.

PMID- 18071862
TI  - Billroth 1 versus Roux-en-Y reconstructions: a quality-of-life survey at 5 years.
AB  - BACKGROUND: In the majority of gastric surgical units across Japan, Billroth 1 is
      the preferred method of anastomosis following subtotal distal gastrectomy for
      gastric cancer. However, across Europe and North America, reconstruction using a
      Roux-en-Y anastomosis is more common. There is a lack of comparative studies of
      the two methods focusing on long-term outcome. This study evaluated patient
      outcome, in terms of adverse gastrointestinal complaints and quality of life, at
      5 years following surgery. METHODS: A total of 652 patients had a subtotal distal
      gastrectomy for early gastric cancer between January 1993 and December 1999. We
      studied 229 patients with reconstruction by the Billroth 1 procedure and 214
      patients with the Roux-en-Y procedure. All patients had an abdominal ultrasound
      and endoscopy as part of their follow-up. Quality of life was assessed by
      questionnaire. RESULTS: We had an 87% response rate from the questionnaire
      assessment. The results demonstrated that patients were less likely to experience
      symptoms of either early or late dumping after Roux-en-Y anastomosis than after
      Billroth 1. In addition, there were significantly fewer patients with gastritis
      on endoscopy in the Roux-en-Y group. There was no significant difference in the
      average relative body weight between the groups. However, patients were more
      likely to develop gallstones after a Roux-en-Y than after a Billroth 1
      reconstruction. CONCLUSION: The results from this study show that, at 5 years,
      both symptomatically and functionally, Roux-en-Y reconstruction was superior to
      the Billroth I method after subtotal distal gastrectomy for gastric cancer.
      However, the overall outcome in both groups was good, with patient satisfaction
      scores of around 75% in each group.

PMID- 18071863
TI  - A study of cancer information for cancer patients on the internet.
AB  - BACKGROUND: There have been few studies of the information provided for cancer
      patients on the internet. METHODS: Using the Japanese language, we searched for
      cancer-related web pages, using the Google search engine, and evaluated the
      characteristics of the 150 top-ranked search results. We collected information on
      the operators of the websites, number of links, existence of a search function,
      and advertisements on the site. According to their contents, the 150 websites
      were classified into seven categories, of which five (numbers 1, 2, 3, 4, and 6)
      each accounted for 20% of the websites. The categories were: (1) media-related
      websites (e.g., newspapers and publishers), and portal sites; (2) patient
      association websites, patient's diaries, blogs by patients and/or their families
      (n = 33); (3) websites of medical institutions (e.g., hospitals; n = 27); (4)
      websites of research institutions (e.g., universities; n = 35); (5) websites of
      pharmaceutical companies; (6) other websites providing medical information (n =
      32); and (7) other websites that did not belong to categories 1-6. Outgoing links
      were common in websites created by media-related organizations (median, 13) or
      patients and their families (median, 15), but such links were not common in the
      other types of websites (median, 0-4). Eight of the 13 cancer based hospitals in
      Japan, as well as the National Cancer Center were publishing general cancer
      information on their websites. Of the 13 cancer based hospitals, 12 included a
      link to the National Cancer Center. The National Cancer Center had the largest
      amount of information (736 575 words), exceeding the amount provided by the other
      cancer based hospitals (1 622-155 515 words). Two of the 7 websites of academic
      associations (included in category 6) had cancer information for patients, but
      the document sizes were small (3230-44 091 words). CONCLUSION: The website of the
      National Cancer Center is the most prominent source of general cancer information
      for patients, but it still has room for improvement in its usability.

PMID- 18071864
TI  - Spontaneous regression of cervical lymph node metastasis in a patient with
      mesopharyngeal squamous cell carcinoma of the tongue: possible association
      between apoptosis and tumor regression.
AB  - BACKGROUND: We report a case of mesopharyngeal squamous cell carcinoma with
      spontaneous regression of lymph node metastasis. Spontaneous regression of lymph
      node metastasis of head and neck carcinoma has not been reported previously.
      Possible causes of the regression of lymph node metastasis include regression of
      lymphocytic division transiently inflated by an immunological stimulus, and en
      bloc tumor necrosis due to degradation of vascularity, such as thromboembolism
      and intranodal hemorrhage. However, the patient's history and repeated imaging
      analyses suggested that these factors were not responsible for the regression. To
      clarify the etiology of this rare phenomenon, we investigated the cause of
      spontaneous regression with analyses of paraffin-embedded sections. METHODS: The
      frequency of cystic lesions, en-bloc necrotic lesions, and apoptosis of carcinoma
      were investigated with immunohistochemical analysis, and these features were
      compared with those in specimens from five other patients with head and neck
      squamous cell carcinoma. RESULTS: The present case revealed no tendency towards
      microscopically confirmed cystic formation or necrosis, but the frequency of
      apoptosis was significantly higher than that in the other five cases. The
      apoptotic tendency was not restricted to the lymph node in which spontaneous
      regression was confirmed clinically, but was also consistently observed in other
      lymph nodes and in the primary lesion that was detected and radically ablated 2
      months after complete neck regional dissection had been done. CONCLUSION: Our
      case may be the first case of squamous cell carcinoma undergoing spontaneous
      regression in which enhanced apoptosis was demonstrated quantitatively. The
      findings were considered to contribute to evidence of spontaneous regression in
      squamous cell carcinoma of the head and neck resulting from enhanced apoptosis.

PMID- 18071865
TI  - Death-resistant and nonresistant malignant human cell lines under anoxia in
      vitro.
AB  - BACKGROUND: Erythropoietin supports the survival of erythroblasts. We previously
      demonstrated that 24 malignant human cell lines expressed erythropoietin and its
      receptor and that erythropoietin secretion was enhanced under anoxia. In this
      study, we examined the viability of 22 of these cell lines excluding two leukemia
      cell lines under anoxia. METHODS: Twenty-two cancer cell lines of various origins
      were cultured under anoxia or normoxia for 4 days, and their viability was
      examined at 1-day intervals. The levels of lactate and ATP were measured. The
      expressions of hypoxia-inducible transcription factor 1alpha (HIF-1alpha) and Bcl
      2 family proteins were examined by western blotting analysis. The cellular and
      mitochondrial features were examined by microscopy. RESULTS: Eleven of the 22
      cancer cell lines examined showed 80% to 100% cell viability after 4 days under
      anoxia; 2 cell lines showed similar viability for 3 days, 3 cell lines showed
      similar viability for 2 days, and 6 cell lines showed similar viability for 1 day
      or less. These 11 death-resistant cell lines, which secrete various amounts of
      erythropoietin under anoxia, produced significantly more lactate during 2 days
      under anoxia than under normoxia, with ATP levels about 60% of those before
      anoxia. ATP returned to the normal level when normoxia was restored after 4 days
      of anoxia. However, the nonresistant cell lines responded to anoxia by yielding
      significantly more lactate without a reduction of the ATP level. The expression
      patterns of Bcl-2 family proteins revealed that apoptosis-inhibiting signals
      predominated over proapoptotic signals in the death-resistant cells under anoxia.
      CONCLUSION: The majority of the cancer cell lines examined survived under anoxia
      in vitro, through the Pasteur effect, in a dormant state without direct support
      of erythropoietin.

PMID- 18071866
TI  - Effectiveness of the treatment-phase of two-phase complex decongestive
      physiotherapy for the treatment of extremity lymphedema.
AB  - BACKGROUND: Complex decongestive physiotherapy (CDP) consists of a two-phase
      treatment program and is the international standard therapy for lymphedema.
      However, this therapy is not performed at most hospitals in Japan. METHODS: The
      subjects of the present study were 82 Japanese women with lymphedema of an
      extremity (median age, 64 years; range, 40-86 years). The volume of the affected
      extremity was compared before and after therapy, and the duration of the CDP
      treatment phase and rate of edema reduction were ascertained. The associations
      between the effect of CDP and duration of lymphedema, operative procedure, and
      radiotherapy were also investigated. RESULTS: For patients with upper-extremity
      lymphedema, the median duration of the CDP treatment phase was 6 treatment days
      (range, 3-26 days), median reduction of edema volume was 328.7 ml (range, 76.6
      1258.0 ml; P = 0.0014), and median rate of edema reduction was 58.9% (range,
      42.7%-97.1%). For patients with lower-extremity lymphedema, the median duration
      of the CDP treatment phase was 10 treatment days (range, 2-35 days), median
      reduction of edema volume was 1573.7 ml (range, 293.9-3471.1 ml; P < 0.0001), and
      median rate of edema reduction was 73.4% (range, 29.2%-117.3%). Although no
      correlation was seen between duration of lymphedema and duration of the CDP
      treatment phase or rate of edema reduction, the degree of lymph node dissection
      tended to influence rate of edema reduction in patients with lower-extremity
      lymphedema. CONCLUSION: In a study of Japanese women with lymphedema, CDP
      comprising a two-phase treatment program was clearly effective.

PMID- 18071867
TI  - Treatment-related ureteral cancer following stage II testicular seminoma.
AB  - We report two cases of left ureteral carcinoma that may have been related to
      prior radiotherapy and anticancer chemotherapy for stage II testicular seminoma.
      Both patients had undergone radiotherapy (60 Gy) and cisplatin-based
      chemotherapy, one 17 years before the present presentation and the other 24 years
      earlier. They underwent retroperitoneoscopy-assisted left nephroureterectomy
      under a diagnosis of left upper ureteral cancer, established by means of
      ureteroscopy and brush biopsy. The urologic and radiologic outcomes have been
      satisfactory after more than 2 years of follow-up. Recently, some investigators
      have reported that testicular cancer survivors are at significantly increased
      risk of solid tumors for at least 35 years after treatment. Young patients may
      have a high risk of cancer when they reach an advanced age.

PMID- 18071868
TI  - Complete response of a patient with advanced gastric cancer, showing Epstein-Barr
      virus infection, to preoperative chemotherapy with S-1 and cisplatin.
AB  - Here we report the case of a patient with advanced gastric cancer with esophageal
      invasion who was treated with chemotherapy using S-1 and cisplatin (CDDP)
      preoperatively. The patient was a 72-year-old woman who was diagnosed with
      advanced gastric cancer (T3N2M0) with esophageal invasion. S-1 was orally
      administered at 80 mg/day (60 mg/m(2) per day) on days 1-14 and CDDP was infused
      at 80 mg/day (60 mg/m(2) per day) on day 8, followed by a 1-week rest. Marked
      reductions in the sizes of the primary tumor and metastatic lymph nodes around
      the stomach were observed after two cycles of the therapy. Adverse reactions
      occurring during the therapy were only grade 2 gastrointestinal disorder and
      grade 1 leukocytopenia. Radiological and endoscopic examinations before surgery
      showed that a partial response (PR) had been achieved. The patient underwent
      curative surgery consisting of total gastrectomy, D2 lymph node dissection, and
      splenectomy. Her postoperative course was uneventful, without surgical
      complications. No gastric cancer cells were detected in the primary lesion or
      lymph nodes by immunohistochemical staining with cytokeratin, confirming a
      histological complete response (CR). As Epstein-Barr virus-encoded small RNA
      (EBER) had been detected by in-situ hybridization in the gastric cancer cells of
      a biopsy specimen, this tumor was diagnosed as an Epstein-Barr virus (EBV)
      associated gastric carcinoma (EBVaGC), which was effectively treated with S-1 and
      cisplatin chemotherapy.

PMID- 18071869
TI  - Synchronous adenocarcinoma and gastrointestinal stromal tumors of the stomach
      treated laparoscopically.
AB  - Gastric adenocarcinomas account for approximately 95% of primary gastric tumors,
      and gastrointestinal stromal tumor (GIST) is the most common gastrointestinal
      mesenchymal tumor, accounting for 1%-3% of primary gastric tumors. However, the
      synchronous occurrence of GIST and gastric epithelial tumor is rare. We herein
      report a case of synchronous occurrence of gastric adenocarcinoma and two GISTs
      of the stomach. All lesions were resected laparoscopically. We discuss this case
      and review the literature.

PMID- 18071870
TI  - Bilateral primary malignant lymphoma of the ureter.
AB  - We report the case of a 68-year-old Japanese man who presented with postrenal
      azotemia due to bilateral upper ureteral stenosis. The patient's right kidney was
      nonfunctional; therefore, right nephroureterectomy was performed for the purpose
      of pathologic diagnosis. Histopathologic examination revealed follicular lymphoma
      with diffuse change in the ureter. With chemotherapy for malignant lymphoma, the
      stenosis of the left ureter was alleviated, and left renal function was
      preserved. Primary malignant lymphoma of the ureter is extremely rare. In cases
      of ureteral stenosis with ureteral wall thickening for which the cause is
      uncertain, the possibility of malignant lymphoma of the ureter should be
      considered.

PMID- 18071871
TI  - Successful 2-year-long remission following repeated salvage surgery in a patient
      with chemotherapy-resistant metastatic nonseminomatous germ cell tumor.
AB  - A 34 year-old man with a diagnosis of nonseminomatous testicular cancer with
      retroperitoneal lymph node metastasis (T1N3M0S2, stage IIIb; intermediate
      prognosis, made after right inguinal orchiectomy was performed) was referred to
      our hospital after having had a total of eight courses of systemic chemotherapy
      and external-beam radiotherapy to the retroperitoneal region in the previous 1
      year. His serum alpha-fetoprotein (AFP) level remained elevated. Two courses of
      paclitaxel, etoposide, and cisplatin combined chemotherapy (TEP; paclitaxel 120
      mg/m(2) day 1, etoposide 80 mg/m(2) days 2-5, cisplatin 20 mg/m(2) days 2-5)
      failed to normalize the AFP level. During the following 2 years he underwent
      salvage surgery four times; infrarenal retroperitoneal lymph node dissection
      (RPLND), left neck lymph node dissection, thoracic duct excision, and suprarenal
      RPLND. Viable cancer cells were found in all surgically resected specimens,
      except for the neck lymph node specimen. The serum AFP level was normalized and
      he has been well without relapse for 2 years after the last surgery. The present
      case suggests that repeated salvage surgery may be beneficial in selected
      patients with a chemotherapy-resistant metastatic germ cell tumor.

PMID- 18071872
TI  - Determination of urethral catheter surface lubricity.
AB  - Device for in-vitro measurement of static and kinetic friction coefficient of
      catheter surface was developed. Tribometer was designed and constructed to work
      with exchangeable counter-faces (polymers, tissue) and various types of tubes, in
      wet conditions in order to mimic in-vivo process. Thus seven commercially
      available urethral catheters, made from vinyl polymers, natural latex with
      silicone coating, all-silicone or hydrogel coated, and one made from
      polyvinylchloride with polyurethane/polyvinylpyrrolidone hydrogel coating
      obtained in our laboratory, were tested against three various counter faces:
      polymethacrylate (organic glass), inner part of porcine aorta and porcine bladder
      mucosa. Additionally, the hydrophility/hydrophobity of tested catheters was
      stated via water wetting contact angle measurement. Super-hydrophilic
      biomaterials revealed low friction on tissue and hydrophobic counter-face;
      slightly hydrophobic showed higher friction in both cases, while more hydrophobic
      manifested low friction on tissue but high on hydrophobic polymer. The smoothest
      friction characteristic was achieved in all cases on tissue counter-faces. The
      measured values of the static coefficient of friction of catheters on bladder
      mucosa counter-face were as follows: the highest (0.15) for vinyl and siliconised
      latex catheters and 3 folds lower (0.05) for all-silicone ones. Hydrogel coated
      catheters exhibited the lowest static and kinetic friction factors.

PMID- 18071873
TI  - Hydroxyapatite coating on Ti6Al4V alloy by a sol-gel method.
AB  - Using trimethyl phosphate and calcium nitrate tetrahydrate as the calcium and
      phosphorus precursors, respectively, HA films were prepared layer by layer by a
      sol-gel method. The phase constitution, microstructure and calcium/phosphorus
      (Ca/P) molar ratio of the sol-gel films were studied by X-ray diffraction (XRD)
      and electronic probe microanalysis (EPMA). The results show that the sol-gel
      films have high crystallinity and are composed of HA and CaO phases, and the Ca/P
      ratio is slightly higher than the theoretical value in HA because of the loss of
      phosphorous element. Two typical cauliflower-like and lamellar structures were
      observed in the films. Cauliflower-like structure, which increases the biological
      reactivity of the implant surface towards natural bone, formed mainly at low
      drying temperature and high calcining temperature, while the lamellar structure
      formed when the drying temperature is high (500 degrees C or above).

PMID- 18071874
TI  - Crystal ageing in irradiated ultra high molecular weight polyethylene.
AB  - Medical grade ultra high molecular weight polyethylene (UHMWPE) of two molecular
      weights has been gamma irradiated in air to give received doses of 3.5 and 10
      Mrad and aged in air for 25 months. Differential scanning calorimetry and wide
      and small angle X-ray diffraction (WAX and SAX) techniques and transmission
      electron microscopy have been used to characterize the materials. Polymer from an
      orthopaedic component, retrieved 10 years after implantation, has been subjected
      to the same analytical programme. The X-ray diffraction data shows that following
      irradiation two events occur with time, first a crystal refinement process,
      indicated by pronounced sharpening of the SAX peak, and secondly growth of a new
      crystal population of reduced lamellae thickness compared to the original crystal
      structures, shown by the development of a bimodal SAX pattern. Following
      irradiation crystallinity increases with time and this second crystal population
      makes a significant contribution to that increase. The retrieved component shows
      full development of these processes. It is considered that these crystallographic
      changes with time are responsible for the observed time dependent changes in the
      mechanical properties of air irradiated UHMWPE.

PMID- 18071875
TI  - Bioactive microspheres produced from gelatin-siloxane hybrids for bone
      regeneration.
AB  - In this study, we produced a novel microsphere with a hybridized composition of
      gelatin and siloxane which is bioactive and degradable for the applications in
      bone regeneration fields. A solution of gelatin organic and siloxane inorganic
      containing calcium chloride was formulated into microspheres in an oil bath
      mediated by a surfactant. Following the processes of hydration, gelation and
      solidification, well-shaped spherical particles were produced with sizes of a few
      to hundreds of micrometers (68 microm on average). The obtained microspheres were
      highly stable in an aqueous solution due to the in situ cross-linking of the
      siloxane with gelatin chains, which eliminated the additional cross-linking step
      generally used in pure gelatin. The hybridized microspheres exhibited rapid
      induction of apatite-like crystals on their surface with incubation in a
      simulated body fluid, suggesting an excellent bone bioactivity in vitro. It is
      considered that the newly developed organic-inorganic microspheres may be useful
      for the regeneration of skeletal defects.

PMID- 18071876
TI  - Angiogenic and cell proliferating action of the natural diarylnonanoids,
      malabaricone B and malabaricone C during healing of indomethacin-induced gastric
      ulceration.
AB  - PURPOSE: To evaluate the plant phenolics, malabaricone B (mal B) and malabaricone
      C (mal C) in healing stomach ulcer by modulating angiogenesis. MATERIALS AND
      METHODS: Male Swiss albino mice, ulcerated with indomethacin (18 mg/kg, p. o.,
      single dose) were treated up to 7 days with different doses of mal B or mal C.
      The healing capacities of the drugs and their effects on the angiogenic
      parameters were assessed. RESULTS: Maximum ulceration, observed on the 3rd day
      after indomethacin administration was effectively healed by mal B and mal C (each
      10 mg/kg, p. o. x 3 days), the latter showing equivalent potency (~78% p < 0.001)
      as that of Omez (3 mg/kg, p. o. x 3 days) and misoprostol (10 mug/kg, p. o. x 3
      days). Compared to the untreated mice, those treated with mal B or mal C
      respectively for 3 days increased the mucosal EGF level (139 and 178%, p <
      0.001), the serum VEGF level (56%, p < 0.01 and 95%, p < 0.001) and microvessels
      formation (37%, p < 0.05 and 62%, p < 0.01), while reducing the serum endostatin
      level (37%, p < 0.05 and 61%, p < 0.01). The relative healing capacities of mal B
      and mal C correlated well with their respective abilities to modulate the
      angiogenic factors. The healing by Omez and misoprostol was not due to improved
      angiogenesis. CONCLUSIONS: The drugs, mal B and mal C could effectively heal
      indomethacin-induced stomach ulceration in mice by promoting angiogenesis.

PMID- 18071877
TI  - Microdomain pH gradient and kinetics inside composite polymeric membranes of pH
      and glucose sensitivity.
AB  - PURPOSE: Polymeric membranes containing pH-sensitive nano-hydrogels and glucose
      oxidase were found to exhibit glucose-responsive insulin release. To verify that
      this glucose-responsiveness stemmed from the decrease in the internal pH of the
      membranes, we determined the spatial and temporal pH profiles inside the
      composite membranes in situ for the first time. MATERIALS AND METHODS: A pH
      sensitive fluorescent dye and an inert internal reference was incorporated in the
      membranes consisting of poly(N-isopropylacrylamide-co-methacrylic acid)
      nanoparticles in a polymer matrix, with or without glucose oxidase and catalase.
      The fluorescence intensity versus time was measured by laser scanning confocal
      microscopy. The intensity ratios of the two fluorescent dyes were used to
      determine the internal pH profiles of the membranes in buffer solutions of
      various pH or glucose levels. RESULTS: The internal pH was found to be lower than
      the external pH of buffer solutions. The pH decreased with an increase in glucose
      concentration, incubation time and the distance towards the center of the
      membranes due to the relative rates of glucose oxidation and solute diffusion.
      CONCLUSIONS: The results provided direct experimental evidence of acidic internal
      pH that inversely related to external glucose concentration in an external medium
      of constant neutral pH.

PMID- 18071878
TI  - CD72 polymorphism associated with child-onset of idiopathic thrombocytopenic
      purpura in Chinese patients.
AB  - Idiopathic thrombocytopenic purpura (ITP) is a disease putatively relating to
      abnormal immune function and auto-antiplatelet immunoglobulin. We examined
      whether polymorphism of CD72, an inhibitory receptor of B cells, affect the
      susceptibility to ITP, or associated with the clinical characteristics of ITP. A
      case-control study was carried out in 206 Chinese ITP patients and 169 healthy
      controls. The detection of variable number of tandem repeats in CD72 intron 8 was
      performed by polymerase chain reaction and subsequent analysis with
      polyacrylamide gel electrophoresis. We did not find direct association between
      CD72 genotypes and susceptibility to ITP. The haplotype that contained one repeat
      of 13 nucleotides in intron 8 (designated as *1, and haplotype containing two
      repeat of 13 nucleotides in intron 8 is designated as *2) was significantly
      associated with early first onset age (< or = 14) in ITP patients (P = 0.03). ITP
      patients with CD72*1?*1 and *1?*2 genotype had a 3.09-fold [95% confidence
      interval (CI), 1.32-7.25] and 1.98-fold (95% CI, 0.92-4.25) increased risk of
      appearing ITP manifestation at their childhood respectively. The haplotype CD72*1
      is apparently a risk allele, whereas CD72*2 a protective allele for child-onset
      of ITP disease.

PMID- 18071879
TI  - Interferon-alpha induces up-regulation and nuclear translocation of the Ro52
      autoantigen as detected by a panel of novel Ro52-specific monoclonal antibodies.
AB  - Interferon-alpha (IFN-alpha) has been implicated in the pathogenesis of Sjogren's
      syndrome and systemic lupus erythematosus. Ro52, which was recently identified as
      an E3 ligase with anti-proliferative and pro-apoptotic properties, is a major
      autoantigen targeted in both these conditions. Microarray analyses have indicated
      up-regulation of Ro52 by IFN-alpha, and the objective of the present study was to
      address the potential link between IFN-alpha and Ro52. To investigate the
      influence of IFN-alpha on Ro52 protein levels and cellular localization, we
      generated a panel of monoclonal antibodies to different domains of Ro52. These
      novel monoclonal antibodies were characterized by immunoprecipitation, Western
      blot, and enzyme-linked immunosorbent assay using cell lysates, recombinant Ro52
      protein, and synthetic peptides. Ro52 was up-regulated in HeLa cells and human B
      cells at the messenger RNA and protein levels in response to IFN-alpha
      stimulation as detected by reverse transcriptase polymerase chain reaction and
      Western blot. After up-regulation, Ro52 translocated from the cytoplasm to the
      nucleus. The nuclear translocation of Ro52 was observed after staining with
      generated monoclonal antibodies specific for both the RING, coiled-coil, and
      B30.2 domains of Ro52 and the nuclear translocation of Ro52 preceded IFN-alpha
      induced apoptotic cell death detected by caspase-3 and TUNEL staining in the
      treated cultures. In conclusion, our data show that IFN-alpha first induces up
      regulation of Ro52 protein and then prompts translocation of the up-regulated
      Ro52 protein in to the nucleus. The translocation precedes apoptosis of the IFN
      alpha exposed cells, suggesting a role for Ro52 in mediating the anti
      proliferative or pro-apoptotic effects of the autoimmune-related cytokine IFN
      alpha.

PMID- 18071880
TI  - I kappa B alpha promoter polymorphisms in patients with systemic lupus
      erythematosus.
AB  - To investigate the associations of IkappaBalpha gene polymorphisms with the
      development and clinical manifestations of systemic lupus erythematosus (SLE),
      110 patients with SLE and 120 unrelated healthy controls were enrolled in this
      study. The IkappaBalpha -881 A/G, -826 C/T, -550 A/T, -519 C/T, and -297 C/T
      polymorphisms were determined by the polymerase chain reaction/reaction fragment
      length polymorphism method. The genotype frequency of IkappaBalpha -826 C/T in
      the patients with SLE was significantly higher than that of the controls (p =
      0.003, OR = 2.2, 95% CI = 1.3-3.9). The SLE patients also have significantly
      higher carriage rate of IkappaBalpha -826 T than the controls (p = 0.01, OR =
      2.0, 95% CI = 1.2-3.4). We also found that the estimated haplotype frequency of
      IkappaBalpha -881A -826T -550A -519C -297C was significantly increased in the
      patients with SLE in comparison with that of the controls. This study also
      demonstrated that the association of IkappaBalpha -826 T with SLE was independent
      of HLA-DR15, which is associated with susceptibility to SLE in Taiwan. Moreover,
      a synergistic effect could also be found between IkappaBalpha -826 T and HLA
      DR15. IkappaBalpha -826 T is associated with the development of SLE in Taiwan.
      The IkappaBalpha -881A -826T -550A -519C -297C haplotype is also associated with
      susceptibility to SLE. This study also demonstrated that IkappaBalpha -881G was
      associated with the occurrence of vasculitis in SLE patients. IkappaBalpha -550T
      might be a protective factor for the development of malar rash.

PMID- 18071881
TI  - Interleukin-10 and tumor necrosis factor-alpha gene polymorphisms in
      tuberculosis.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease
      in humans killing nearly three million people and eight million cases annually.
      The cytokines TNF-alpha and IL-10 have been implicated in the pathogenesis of TB.
      Certain single nucleotide polymorphisms within the promoter region of the IL10
      and TNF genes have been associated with altered levels of circulating IL10 and
      TNF-alpha. We analyzed TNF-alpha (-308 G/A, -238 G/A, -376 G/A) and IL10 (-1,082
      G/A, -819 C/T, -592 C/A) polymorphisms in 128 patients with TB and 80 healthy
      subjects using by amplification refractory mutation system-polymerase chain
      reaction (ARMS-PCR). A significant association was found between TB and -1,082 G
      allele (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41). Significant difference was
      observed in IL10 GCC and ACC haplotypes distribution between TB and control
      subjects (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41; Pc: 0.004, O.R 0.53, 95% CI 0.35
      0.81). No statistically significant association was found between IL-10 -819 C/T,
      TNF-alpha 308 G/A, -238 G/A, -376 G/A polymorphisms, functional TNFalpha/IL-10
      genotypes and TB. Our findings suggest that IL-10 1082 G/A alleles or haplotypes
      containing these alleles may influence the Th1/Th2 balance and hence may play a
      role in TB susceptibility and increase risk of developing disease. This
      polymorphism may be one of the many genetic factors affecting disease outcome.

PMID- 18071882
TI  - Significance of transporter associated with antigen processing 2 (TAP2) gene
      polymorphisms in susceptibility to dengue viral infection.
AB  - BACKGROUND AND AIMS: The polymorphic transporter associated with antigen
      processing (TAP)1 and TAP2 genes encode subunits of the transporter that delivers
      peptides to the human leukocyte antigen class I molecules. Because the
      polymorphism of the TAP genes has been shown to affect peptide transport, it has
      been suggested that TAP genes are potential regulators of the immune response. We
      recently reported that TAP1 gene polymorphism is associated with severe dengue
      infection. This study was carried out to elucidate whether TAP2 polymorphisms are
      involved in diverse pathogenesis of dengue infection. MATERIALS AND METHODS: This
      study included 100 controls and 197 dengue-infected patients who were further
      categorized into 90 dengue fever (DF) cases, 75 dengue hemorrhagic fever cases
      (DHF), and 32 dengue shock syndrome (DSS) cases as per WHO grading system. TAP2
      gene polymorphisms were determined by amplification refraction mutation system
      polymerase chain reaction. RESULTS: The frequency of isoleucine at TAP2 379
      (34.5%) was increased among DHF in comparison to controls (21%, P = 0.014). DHF
      cases were more likely to be heterozygous at TAP2 379 (50.7%) than controls [24%,
      odds ratio (OR) = 2.11, P = 0.001]. Significantly high proportion of DHF was
      found to have TAP2 665 threonine/alanine (THR/ALA) genotypes (30.7%) when
      compared with DF (13.3%, OR = 2.3, P = 0.006) cases. There was no difference in
      the genotypes studied between DSS and controls or DF or DHF. CONCLUSION: This
      first report on TAP 2 gene polymorphism in dengue suggested that heterozygous
      pattern at TAP2 379 locus confers susceptibility to DHF, and TAP2 665 THR/ALA
      genotype was found to be a risk factor for development of DHF.

PMID- 18071883
TI  - Fc gamma RI-mediated activation of human mast cells promotes survival and
      induction of the pro-survival gene Bfl-1.
AB  - Activation of mast cells through either FcepsilonRI or FcgammaRI leads to release
      of mediators contributing to the inflammatory response. One of the biologic
      characteristics of mast cells in allergic pathology is that these cells have the
      capacity to recover and regranulate after aggregation of FcepsilonRI. We have
      previously demonstrated that the pro-survival protein A1/Bfl-1 is required for
      mast cells to survive IgE-mediated activation. In the present study, we have
      investigated whether human mast cells show similar induction of bfl-1 and
      activation-induced survival after aggregation of FcgammaRI. Human cord blood
      derived mast cells were activated by aggregation of either FcepsilonRI or
      FcgammaRI, and activation-induced survival and induction of bfl-1 was measured.
      We found that aggregation of FcgammaRI-induced expression of Bfl-1 and caused a
      comparable activation-induced mast cell survival as FcepsilonRI does. These data
      suggests that activation through Fc-receptors contribute to mast cell survival
      during antibody-dependent mast cell mediated inflammatory responses.

PMID- 18071884
TI  - Blimp-1 connects the intrinsic and extrinsic regulation of T cell homeostasis.
AB  - The body tends to maintain a relatively constant number of peripheral T cells, a
      phenomenon termed T cell homeostasis. Homeostasis is controlled by the
      coordinated activity of extrinsic regulation, most notably through cytokines of
      the common gamma chain (cgammaC) family and intrinsic regulation by transcription
      factors. Whereas the former mechanism has been extensively studied and is
      relatively well characterized, the transcription factors that govern the
      homeostasis of late-stage effector and memory T cells have been less well defined
      but include regulators such as T-bet, Eomes, Bcl6, and Id2. The transcriptional
      repressor, Blimp-1 is well known as a master regulator of the terminal
      differentiation of B cells into antibody secreting plasma cells. Recent
      experiments have now revealed that Blimp-1 is also a key regulator of T cell
      differentiation. Blimp-1 is expressed in differentiated effector T cells and
      controls their homeostasis. Interestingly, Blimp-1 expression is controlled by
      the same cgammaC cytokines that regulate T cell homeostasis suggesting a direct
      link between the extrinsic and intrinsic arms of the process.

PMID- 18071885
TI  - Contribution of the conserved A16Leu to insulin foldability.
AB  - Contributions of the evolutionarily conserved A16Leu and B17Leu to insulin
      foldability were characterized by evaluating folding properties of single-chain
      insulin analogs. The results showed A16Leu had much more significant effects on
      the foldability of insulin than B17Leu.

PMID- 18071887
TI  - Prediction of the beta-hairpins in proteins using support vector machine.
AB  - By using of the composite vector with increment of diversity and scoring function
      to express the information of sequence, a support vector machine (SVM) algorithm
      for predicting beta-hairpin motifs is proposed. The prediction is done on a
      dataset of 3,088 non homologous proteins containing 6,027 beta-hairpins. The
      overall accuracy of prediction and Matthew's correlation coefficient are 79.9%
      and 0.59 for the independent testing dataset. In addition, a higher accuracy of
      83.3% and Matthew's correlation coefficient of 0.67 in the independent testing
      dataset are obtained on a dataset previously used by Kumar et al. (Nuclic Acid
      Res 33:154-159). The performance of the method is also evaluated by predicting
      the beta-hairpins of in the CASP6 proteins, and the better results are obtained.
      Moreover, this method is used to predict four kinds of supersecondary structures.
      The overall accuracy of prediction is 64.5% for the independent testing dataset.

PMID- 18071886
TI  - Phosphorylation of recombinant tristetraprolin in vitro.
AB  - Tristetraprolin/zinc finger protein 36 (TTP/ ZFP36) binds and destabilizes some
      proinflammatory cytokine mRNAs. TTP-deficient mice develop a profound
      inflammatory syndrome due to excessive production of proinflammatory cytokines.
      TTP gene expression is induced by various factors including insulin, cinnamon,
      and green tea extracts. Previous studies have shown that TTP is highly
      phosphorylated in vivo and multiple phosphorylation sites are identified in human
      TTP. This study evaluated the potential protein kinases that could phosphorylate
      recombinant TTP in vitro. Motif scanning suggested that TTP was a potential
      substrate for various kinases. SDS-PAGE showed that in vitro phosphorylation of
      TTP with p42 and p38 MAP kinases resulted in visible electrophoretic mobility
      shift of TTP to higher molecular masses. Autoradiography showed that TTP was
      phosphorylated in vitro by GSK3b, PKA, PKB, PKC, but not Cdc2, in addition to
      p42, p38, and JNK. These results demonstrate that TTP is a substrate for a number
      of protein kinases in vitro.

PMID- 18071888
TI  - Psychiatric disorders in clinical genetics II: Individualizing recurrence risks.
AB  - This is the second article of a two-part professional development series on
      genetic counseling for personal and family histories of psychiatric disorders. It
      is based on an Educational Breakout Session presented by The Psychiatric Special
      Interest Group of the National Society of Genetic Counselors at the 2006 Annual
      Education Conference. While the first article in this two part series dealt with
      addressing family histories of psychiatric disorders in clinical practice, the
      following discussion deals with the generation and provision of individualized
      recurrence risks for psychiatric disorders, based on empiric risk data. We
      present four cases that illustrate important components of and process for
      generating individualized risk assessment for family histories of psychiatric
      disorders.

PMID- 18071889
TI  - Surgery for atrial fibrillation: current state-of-the-art.

PMID- 18071890
TI  - Complete nucleotide sequence of a new strain of Tobacco necrosis virus A
      infecting soybean in China and infectivity of its full-length cDNA clone.
AB  - The complete nucleotide sequence of a virus isolated from soybean (Glycine max
      (L.) Merr.) in China, previously identified as a new strain of Tobacco necrosis
      virus A (TNV-A) based on its biological, serological properties, and coat protein
      (CP) sequence and named as TNV-A C, was determined and compared with that of TNV
      A and other closely related Necroviruses and Carmoviruses. The viral RNA genome
      consists of 3,682 nucleotides and contains five open reading frames (ORFs). TNV-A
      C showed 86.4% overall nucleotide sequence identity to TNV-A. The CP and putative
      RNA-dependent RNA polymerase (RdRp) showed 88.8 and 95.9% amino acid identity,
      respectively, to that of TNV-A. The greatest difference between TNV-A C and TNV-A
      was in the 3' terminal region: the p7K ORF region present in TNV-A was absent in
      TNV-A C. Phylogenetic analysis of RdRp, CP, and small ORF regions of Necroviruses
      confirmed TNV-A C as a new strain of TNV-A. A full-length cDNA clone of TNV-A C
      was constructed and used as template for run-off transcription based on the
      obtained sequence. The results indicate that the in vitro-synthesized viral RNA
      faithfully represented the biological activity of wild-type TNV-A C.

PMID- 18071891
TI  - Genotyping of human bocavirus using a restriction length polymorphism.
AB  - Sequencing analysis of the isolates of a recently identified pathogen associated
      with respiratory infections, human bocavirus (HBoV), allowed for identification
      of two virus genotypes of the virus. In the current article a new method for a
      simple and fast differentiation of HBoV genotypes in clinical materials is
      described. The test includes an amplification of a 309 bp fragment of VP1/VP2
      gene of HBoV from nasopharyngeal aspirates with a subsequent incubation of a PCR
      mix with the BstAPI endonuclease. Upon such a digestion, the DNA fragment derived
      from the genotype I HBoV isolates forms two fragments of 150 and 159 bp, while
      that obtained from genotype 2 isolates remains unrestricted. The developed
      technique may be used in epidemiological studies of HBoV infection and analysis
      of the potential differences in biological characteristics of HboV genotypes.

PMID- 18071892
TI  - Role of the 25-26 nt siRNA in the resistance of transgenic Prunus domestica graft
      inoculated with plum pox virus.
AB  - The reaction of a genetically engineered plum clone (C5) resistant to plum pox
      virus (PPV) by graft inoculation with the virus was evaluated. The resistance in
      this clone has been demonstrated to be mediated through post-transcriptional gene
      silencing (PTGS). A single C5 plant out of 30 plants inoculated with PPV M strain
      by double chip-budding showed mild diffuse mosaic 'Sharka' symptom at the bottom
      section of the scion. The upper leaves of this PPV-infected C5 plant remained
      symptomless and the virus was not detected in them by either DAS-ELISA or RT-PCR.
      An RNA silencing associated small interfering RNA duplex, siRNA (21-26 nt), was
      detected in non-inoculated C5 plants and in the portions of inoculated C5 plant
      in which PPV could not be detected. In the PPV-infected portion of the C5 plant
      and in C6 PPV susceptible plants only the approximately 21-22 nt siRNAs was
      detected. Cytosine-methylation was confirmed in C5 plants both uninfected and
      showing PPV symptoms. The 25-26 nt siRNA normally present in C5 was absent in PPV
      infected C5 tissues confirming the critical role of this siRNA in the resistance
      of clone C5 to PPV infection. We also show that this PPV infection was limited
      and transient. It was only detected in one plant at one of four post-dormancy
      sampling dates and did not appear to affect the overall PPV resistance of the C5
      clone.

PMID- 18071893
TI  - Speed, variability, and timing of motor output in ADHD: which measures are useful
      for endophenotypic research?
AB  - Attention-Deficit/Hyperactivity Disorder (ADHD) shares a genetic basis with motor
      coordination problems and probably motor timing problems. In line with this,
      comparable problems in motor timing should be observed in first degree relatives
      and might, therefore, form a suitable endophenotypic candidate. This hypothesis
      was investigated in 238 ADHD-families (545 children) and 147 control-families
      (271 children). A motor timing task was administered, in which children had to
      produce a 1,000 ms interval. In addition to this task, two basic motor tasks were
      administered to examine speed and variability of motor output, when no timing
      component was required. Results indicated that variability in motor timing is a
      useful endophenotypic candidate: It was clearly associated with ADHD, it was also
      present in non-affected siblings, and it correlated within families. Accuracy
      (under- versus over-production) in motor timing appeared less useful: Even though
      accuracy was associated with ADHD (probands and affected siblings had a tendency
      to under-produce the 1,000 ms interval compared to controls), non-affected
      siblings did not differ from controls and sibling correlations were only
      marginally significant. Slow and variable motor output without timing component
      also appears present in ADHD, but not in non-affected siblings, suggesting these
      deficits not to be related to a familial vulnerability for ADHD. Deficits in
      motor timing could not be explained by deficits already present in basic motor
      output without a timing component. This suggests abnormalities in motor timing
      were predominantly related to deficient motor timing processes and not to general
      deficient motor functioning. The finding that deficits in motor timing run in
      ADHD-families suggests this to be a fruitful domain for further exploration in
      relation to the genetic underpinnings of ADHD.

PMID- 18071894
TI  - A daily process investigation of alcohol-involved sexual risk behavior among
      economically disadvantaged problem drinkers living with HIV/AIDS.
AB  - Alcohol use is believed to increase sexual risk behavior among people living with
      HIV/AIDS (PLWHA). As drinking and sexual risk acts often occur in the same social
      contexts, this association is difficult to confirm. In this study, electronic
      daily diaries were completed by 116 PLWHA over 5 weeks. This yielded a total of
      1,464 records consisting of data pertaining to discrete occasions of anal and
      vaginal sex. Simultaneous within- and between-person multilevel analyses were
      conducted, including situational variables (partner type, partner serostatus,
      partner drinking) and individual difference variables (gender, level of alcohol
      dependence). The resulting model explains 27.5% of the variance and reveals that
      interactions among these situational and individual difference variables predict
      changes in the estimated rate of unprotected sex (US). Also, in defined contexts,
      the amount of alcohol consumed prior to sex significantly affects the rate of US
      among members of the sample. Implications are discussed.

PMID- 18071895
TI  - Update on the use of dehydroepiandrosterone supplementation among women with
      diminished ovarian function.
AB  - OBJECTIVE: We assessed the role of DHEA supplementation on pregnancy rates in
      women with diminished ovarian function. DESIGN: This is a case control study of
      190 women with diminished ovarian function. The study group includes 89 patients
      who used supplementation with 75 mg daily of oral, micronized DHEA for up to 4
      months prior to entry into in vitro fertilization (IVF). The control group is
      composed of 101 couples who received infertility treatment, but did not use DHEA.
      The primary outcome was clinical pregnancy after the patient's initial visit. We
      developed a Cox proportional hazards model to compare the proportional hazards of
      pregnancy among women using DHEA with the controls group. RESULTS: Cumulative
      clinical pregnancy rates were significantly higher in the study group (25
      pregnancies; 28.4% vs. 11 pregnancies; 11.9%; relative hazard of pregnancy in
      study group (HR 3.8; 95% CI 1.2-11.8; p < 0.05). CONCLUSIONS: DHEA treatment
      resulted in significantly higher cumulative pregnancy rates. These data support a
      beneficial effect of DHEA supplementation among women with diminished ovarian
      function.

PMID- 18071896
TI  - Current and past maternal depression, maternal interaction behaviors, and
      children's externalizing and internalizing symptoms.
AB  - Relations among past maternal depressive disorder, current depressive symptoms,
      current maternal interaction behaviors, and children's adjustment were examined
      in a sample of 204 women and their young adolescent offspring (mean age = 11.86,
      SD = 0.55). Mothers either had (n = 157) or had not (n = 57) experienced at least
      one depressive disorder during the child's life. Mothers and children
      participated in a problem-solving task, video-taped for later coding. Mothers
      with current depressive symptoms and those with histories of chronic/severe
      depressive disorders displayed fewer positive behaviors toward their children;
      mothers with current depressive symptoms also showed more negative behaviors with
      their children. The relation between mothers' depression history and their
      behavior during the interaction with their child was partially mediated by
      mothers' current mood state. Moreover, high levels of maternal negativity and low
      levels of positivity during the problem-solving task were related to children's
      externalizing problems. Maternal positivity partially mediated the relation
      between maternal depression and children's externalizing symptoms. These findings
      highlight the importance of providing parenting interventions for depressed
      mothers.

PMID- 18071897
TI  - Symptom perception in CHF: (why mind matters).
AB  - Symptoms utilized in the clinical care of heart failure as markers of disease
      severity include, dyspnea, insomnia, low energy, fatigue, poor appetite, and
      diminished memory. This is despite the fact that physiologic variables such as
      cardiac ejection fraction and oxygen consumption do not accurately predict
      functional state in individuals with congestive heart failure (CHF). Distress
      (anxiety and depression) may amplify symptom complaints without associated
      physiologic aberration. Personality traits and psychiatric illness, such as mood,
      anxiety, and psychotic illnesses may also alter perception of somatic symptoms
      that are associated with this chronic illness. The impact of distress and its
      treatment on functional performance and CHF symptom reporting deserve additional
      attention. The need to screen for distress in all with serious symptomatic heart
      failure is certain.

PMID- 18071898
TI  - Counselor and client characteristics in mental health versus substance abuse
      treatment settings providing services for co-occurring disorders.
AB  - The study compares counselor and client characteristics of state-funded co
      occurring disorder (COPSD) programs in mental health (MH) versus substance abuse
      (SA) settings. SA counselors more often had graduate degrees and MH counselors
      rated their knowledge and skills lower on two of nine COPSD best practice
      principles. MH clients were more frequently diagnosed with schizophrenia,
      depression, and bipolar disorder, whereas SA clients displayed evidence of
      greater substance use severity and had higher rates of treatment completion and
      abstinence at discharge. Results reveal significant implications for workforce
      development and potential system changes to enhance COPSD services that are
      unique to each setting.

PMID- 18071899
TI  - Predicting subjective quality of life in workers with severe psychiatric
      disabilities.
AB  - Research has found that, although work may not provide comprehensive benefits for
      people with psychiatric disabilities, it does help them live more satisfactory
      lives. A self-report questionnaire that incorporated several scales was
      administrated to 134 persons with severe psychiatric disabilities working under
      different workplace conditions to find out what factors most contributed to
      perceptions of job satisfaction and quality of life. The study found that
      subjective quality of life was directly influenced by mental health functioning,
      informal social support, and job satisfaction, and indirectly influenced by
      perceived life stress and formal social support.

PMID- 18071900
TI  - Clinical outcomes of integrated psychiatric and general medical care.
AB  - This pilot study explored the feasibility of providing integrated primary and
      psychiatric care in a primary care setting and compared preliminary outcomes to
      those from a traditional care model. The study population consisted of 23
      patients who received integrated medical and psychiatric care in a primary care
      clinic and 23 comparison patients who received medical care in a primary care
      clinic and psychiatric care in a separate mental health clinic. This study
      suggests that integrated care can be provided to chronically mentally ill
      patients in a primary care setting and generate outcomes comparable to those of
      standard care.

PMID- 18071901
TI  - The "lost boys" of Sudan: use of health services and functional health outcomes
      of unaccompanied refugee minors resettled in the U.S.
AB  - To assess whether mental health counseling and other health services were
      associated with functional health outcomes of unaccompanied Sudanese refugee
      minors in the U.S., this study was a descriptive survey of 304 Sudanese refugee
      minors in foster care through the U.S. Unaccompanied Refugee Minors Program
      (URMP). Functional health outcomes included scores of Child Health Questionnaire
      (CHQ) scales and questions regarding care for symptoms or problems associated
      with behavioral disorders, i.e. somatization. Posttraumatic stress disorder
      (PTSD) was assessed using the Harvard Trauma Questionnaire (HTQ). Health services
      questions derived from the National Health Interview Survey. Minors reported high
      rates of counseling (45%); however no differences were noted in counseling use by
      those with PTSD compared with others. Counseling was not associated with health
      outcomes. The majority (76%) reported seeking medical care for symptoms or
      problems often associated with behavioral and emotional problems; however such
      care-seeking was more common among those with PTSD (OR = 2.5, 95% CI = 1.004
      6.26). Through the efforts of the URMP, the Sudanese unaccompanied minors
      received high levels of psychosocial support despite the absence of their
      biological parents. Those with worse functional health were no more likely than
      others to have received mental health counseling while being more likely to seek
      care from any health professional. This was also the case for those with PTSD
      compared to those without it. In linear regression analyses, reported receipt of
      mental health counseling did not impact either positively or negatively on the
      score of any CHQ scale.

PMID- 18071902
TI  - Smoking patterns within a primary care sample of resettled Bosnian refugees.
AB  - The interconnections among smoking status, severity of nicotine related physical
      dependence (NRPD), posttraumatic stress disorder (PTSD)-related physiological
      arousal and subjective health were explored within a sample of 66 resettled
      Bosnian refugees seeking primary healthcare services. Fifty-nine percent (n =
      39/66) of the participants reported that they were current smokers and 44% (n =
      29/66) indicated that they had smoked prior to the war. Both pre-war smoking and
      PTSD arousal independently predicted current smoking. In addition, total PTSD
      arousal and individual symptoms of sleep difficulties, irritability,
      concentration, and hypervigilance were significantly and positively associated
      with NRPD. Severity of PTSD arousal and age uniquely predicted NRPD. While poorer
      subjective health was significantly associated with positive current smoking
      status, neither poorer subjective health nor severity of PTSD arousal was
      significantly associated with interest in quitting/reducing smoking. Findings
      were discussed within the context of culture and stressor-related issues.

PMID- 18071903
TI  - Risks of non-familial violent physical and emotional victimization in four Asian
      ethnic groups.
AB  - BACKGROUND: There is a paucity of research addressing victimization among Asian
      and Southeast Asian youth. METHODS: A community-based sample of 329 Chinese,
      Cambodian, Lao/Mien, and Vietnamese youth were interviewed in a face-to-face
      format. Non-familial physical and emotional victimization were explored in
      relation to risk factors. RESULTS: Results revealed that reporting of violent
      physical victimization was generally greater among males than females, and
      greater among females than males for emotional victimization. Southeast Asian
      youth were more likely to experience victimization than Chinese youth. Violent
      offending, drug use, and delinquent peer affiliation significantly increased the
      odds of physical victimization, whereas more distal influences such as
      neighborhood exerted less influence. For emotional victimization, self-esteem and
      dating abuse was most salient. DISCUSSION: Study highlighted the need to consider
      victimization disaggregated by ethnicities as well as cultural factors that have
      thus far been eclipsed in most empirical studies of youth victimization.

PMID- 18071904
TI  - Caspase-dependent BRCA1 cleavage facilitates chemotherapy-induced apoptosis.
AB  - BRCA1 acts as a tumor suppressor gene, and germ-line mutations in this gene are
      found in a large proportion of families with breast and ovarian cancers. The
      BRCA1 protein has been implicated in several cellular processes, such as
      transcription regulation, DNA responses to DNA damage signals, cell cycle
      control, and apoptosis. Apoptosis plays a critical role in radiation- and
      chemotherapy-induced cytotoxicity, and its impairment contributes to resistance
      to tumor treatments. In an attempt to elucidate the role of BRCA1 in apoptosis,
      we examined the response to chemotherapeutic drugs of cells expressing
      physiological levels of BRCA1 protein. We showed that chemotherapy-induced
      apoptosis leads to a caspase-mediated cleavage of BRCA1. We then showed that the
      BRCA1-p90 cleavage product is mainly localized in the cytoplasm. Finally, we
      demonstrated that cancer-associated mutations affecting the BRCT tandem repeat
      abolish its pro-apoptotic function. The data presented here provide new insight
      into the role of endogenous BRCA1 as a mediator of apoptosis and show that BRCA1
      functions as a molecular determinant of response to a range of cytotoxic
      chemotherapeutic agents.

PMID- 18071905
TI  - RGD-avidin-biotin pretargeting to alpha v beta 3 integrin enhances the
      proapoptotic activity of TNF alpha related apoptosis inducing ligand (TRAIL).
AB  - Recombinant TNF-related apoptosis-inducing ligand (TRAIL) is considered a
      powerful and selective inducer of tumor cell death. We hypothesize that TRAIL's
      potential as anticancer agent can be enhanced further by promoting its
      accumulation in tumor tissue. For this purpose, we developed TRAIL complexes that
      bind to angiogenic endothelial cells. We employed an avidin-biotin pretargeting
      approach, in which biotinylated TRAIL interacted with RGD-equipped avidin. The
      assembled complexes killed tumor cells (Jurkat T cells) via apoptosis induction.
      Furthermore, we demonstrated that the association of the RGD-avidin-TRAIL complex
      onto endothelial cells enhanced the tumor cell killing activity. Endothelial
      cells were not killed by TRAIL nor its derived complexes. Our approach can
      facilitate the enrichment of TRAIL onto angiogenic blood vessels, which may
      enhance intratumoral accumulation. Furthermore, it offers a versatile technology
      for the complexation of targeting ligands with therapeutic recombinant proteins
      and by this a novel way to enhance their specificity and activity.

PMID- 18071906
TI  - Akt and XIAP regulate the sensitivity of human uterine cancer cells to cisplatin,
      doxorubicin and taxol.
AB  - We have investigated the interrelationship between two anti-apoptotic factors,
      XIAP and Akt, and their role in chemoresistance of uterine cancer cells. We used
      one cervical cancer cell line (HeLa) and two endometrial cancer cell lines (KLE
      and Ishikawa) as a model. The three drugs decreased Akt and XIAP content and
      induced apoptosis in P-Akt-negative HeLa cells. In P-Akt1/3-positive Ishikawa
      cells apoptosis induction correlated with XIAP decrease. P-Akt1/2/3-positive KLE
      cells showed maximum chemoresistance as XIAP and Akt levels/phosphorylation
      remained stable in response to the three drugs, and only cisplatin could
      significantly induce apoptosis. We found that XIAP and Akt were functionally
      linked in uterine cancer cells, as downregulation of XIAP with RNAi decreased P
      Akt levels, and inhibition of PI3-K/Akt activity using LY294002 decreased XIAP
      content. Overexpression of constitutively active Akt isoforms in HeLa cells
      induced isoform-specific sensitivity to doxorubicin and taxol but not cisplatin.
      XIAP RNAi increased the cell-specific sensitivity to cisplatin and doxorubicin
      but not taxol. Finally, we found P-Akt immunoreactivity in epithelial cells from
      multiple human endometrial carcinoma tumors, suggesting that Akt may also
      regulate chemosensitivity in uterine cancers in vivo. Altogether these results
      highlight an intertwined role for specific Akt isoforms and XIAP in
      chemoresistance of uterine cancer cells.

PMID- 18071907
TI  - Dielectrophoretic oocyte selection chip for in vitro fertilization.
AB  - This paper reports a new dielectrophoretic separation method of porcine oocytes
      for in vitro fertilization. Conventional manual selection of oocyte highly
      depends on the expert's experience and lacks universal standards for identifying
      the quality of oocyte. In this study, an electrode array chip with castellated
      shape was developed to evaluate dielectrophoretic velocities of oocytes, under
      applied bias conditions with an AC 3 V waveform at 1 MHz for 15 s. Based on
      different dielectrophoresis (DEP) response, the selected group of oocytes that
      moved showed a better developmental potential than the group of oocytes that
      stayed, representing a higher rate of blastocyst formation and a lower rate of
      polyspermic fertilization. In addition, the overall developmental potential of
      oocytes selected by the DEP device was comparable to that of oocytes selected by
      conventional manual method. These results demonstrate that the difference in
      dielectrophoretic velocity can be used to establish an objective criterion for
      the selection of oocytes. Consequently, this method will open the possibility to
      develop an automatic tool for oocyte selection, which would be helpful for
      assisted reproductive technologies such as transgenic and clonal animal
      production.

PMID- 18071908
TI  - Generation of concentration gradient from a wave-like pattern by high frequency
      vibration of liquid-liquid interface.
AB  - The fast and effective generation of a concentration gradient by mixing in the
      microchannel is important for many microfluidic applications. The active control
      of gradient is useful for applying the measurement of cell responses by dynamic
      change of environment. The main purpose of this paper is the generation of
      temporally stable concentration gradient actively. For this purpose, the wave
      like pattern of the liquid-liquid interface is produced in the microchannel. In
      this technique, the high frequency of the wave-like pattern is necessary for
      reducing the length of the mixing path. High frequency of the wave-like pattern
      is achieved by employing the newly developed microvalve using tailor-made
      multilayer piezoelectric actuators (TAMPA) that is compact yet produces large
      displacements and forces. This paper first details the concept for the
      concentration gradient generation method. Next, a microvalve (20 x 15 x 15 mm)
      was designed and produced using TAMPA (8.5 x 10 x 10 mm). Finally, a
      concentration gradient in two-layered flow was generated with the microvalve. As
      a result, the generation of a concentration gradient in two-layered flow with
      active mixing was achieved. Furthermore, it is shown that the concentration
      gradient can be controlled actively by adjusting the input voltage to TAMPA.

PMID- 18071909
TI  - Modeling the inhibition of quadruple mutant Plasmodium falciparum dihydrofolate
      reductase by pyrimethamine derivatives.
AB  - Modeling studies were performed on known inhibitors of the quadruple mutant
      Plasmodium falciparum dihydrofolate reductase (DHFR). GOLD was used to dock 32
      pyrimethamine derivatives into the active site of DHFR obtained from the x-ray
      crystal structure 1J3K.pdb. Several scoring functions were evaluated and the
      Molegro Protein-Ligand Interaction Score was determined to have one of the best
      correlation to experimental pK ( i ). In conjunction with Protein-Ligand
      Interaction scores, predicted binding modes and key protein-ligand interactions
      were evaluated and analyzed in order to develop criteria for selecting compounds
      having a greater chance of activity versus resistant strains of Plasmodium
      falciparum. This methodology will be used in future studies for selection of
      compounds for focused screening libraries.

PMID- 18071910
TI  - Detection of Alpha and Gamma-Proteobacteria in Amblyomma triste (Acari: Ixodidae)
      from Uruguay.
AB  - Amblyomma triste is the most prevalent tick species reported in human tick bites
      in Uruguay and has been found to be infected with Rickettsia parkeri, but no
      other microorganisms have been reported from this tick. A sample of 254 adults of
      A. triste was collected by flagging on vegetation in suburban areas in southern
      Uruguay. Pools of five ticks were assembled and a screening for the DNA from the
      resulting 51 pools was realized by PCR assays using primers for amplifying a
      fragment of 16S rRNA gene for members of Anaplasmataceae. Seventeen pools were
      positive (33%) and the sequenciation of the gene fragment amplified revealed the
      presence of a putative new Alpha-Proteobacterium (denominated Atri-uru). The
      phylogenetic analysis showed that this microorganism is closely related to the
      symbiont of I. ricinus denominated 'Candidatus Midichloria mitochondrii' and
      other associated organisms. This rickettsial symbiont of ticks is included in a
      recent new clade proposed for the Alpha subclass of the Proteobacteria. The
      discovery of this bacterium in A. triste is the first evidence of this group of
      Rickettsiales detected in the Genus Amblyomma, and the first record in South
      America. Also, in two of 17 positive samples a Gamma-Proteobacterium related to
      Francisella-like organisms was detected.

PMID- 18071911
TI  - Tumoral and macrophage uPAR and MMP-9 contribute to the invasiveness of B16
      murine melanoma cells.
AB  - The aim of this study was to investigate whether tumor cells as well as tumor
      associated macrophages (TAMs) contribute to the generation of protease activities
      essential to tumor cell invasiveness, such as matrix metalloproteinase 2 and 9
      (MMP-2 and MMP-9), and the urokinase-type plasminogen activator (uPA) and uPA
      receptor (uPAR). We found that the enhanced invasiveness through Matrigel-coated
      filters of B16 murine melanoma cells stimulated with IFNgamma was associated with
      an higher expression of uPAR and MMP-9 in these cells. Moreover, treatment with
      anti-MMP-9 or anti-uPAR monoclonal antibodies abrogated the increase of
      invasiveness in IFNgamma-stimulated melanoma cells, suggesting a cooperation of
      uPA system and MMP-9 in cytokine-stimulated invasiveness. Invasiveness through
      Matrigel was also enhanced in B16 melanoma cells exposed to a medium conditioned
      by TAMs, represented in our experimental model by thioglycollate-elicited
      macrophages co-cultivated with melanoma cells. Macrophages isolated from these co
      cultures were found to express higher levels of uPAR and MMP-9 compared to
      macrophage cultures alone, and the pro-invasive activity of the co-culture
      conditioned medium was abrogated by anti-MMP-9 monoclonal antibodies, but not
      anti-uPAR monoclonal antibodies. Furthermore, the enhanced uPAR and MMP-9
      expression in macrophages co-cultivated with tumor cells seems a rather specific
      phenomenon, generated through a cell-to-cell contact mechanism. On the whole, our
      data point to a cooperation between tumor cells and macrophages elicited by tumor
      cells themselves in generating key enzymes essential in the promotion of tumor
      invasiveness, such as uPAR and MMP-9.

PMID- 18071912
TI  - Clonal diversity in carcinomas: its implications for tumour progression and the
      contribution made to it by epithelial-mesenchymal transitions.
AB  - The progression of tumours to malignancy is commonly considered to arise through
      lineal evolution, a process in which mutations conferring pro-oncogenic cellular
      phenotypes are acquired by a succession of ever-more dominant clones. However,
      this model is at odds with the persistent polyclonality observed in many cancers.
      We propose that an alternative mechanism for tumour progression, called
      interclonal cooperativity, is likely to play a role at stages of tumour
      progression when mutations cause microenvironmental changes, such as occur with
      epithelial-mesenchymal transitions (EMTs). Interclonal cooperativity occurs when
      cancer cell-cancer cell interactions produce an emergent malignant phenotype from
      individually non-malignant clones. In interclonal cooperativity, the oncogenic
      mutations occur in different clones within the tumour that complement each other
      and cooperate in order to drive progression. This reconciles the accepted genetic
      and evolutionary basis of cancers with the observed polyclonality in tumours.
      Here, we provide a conceptual basis for examining the importance of cancer cell
      cancer cell interactions to the behaviour of tumours and propose specific
      mechanisms by which clonal diversity in tumours, including that provided by EMTs,
      can drive the progression of tumours to malignancy.

PMID- 18071913
TI  - Inhibition of the CXCR4/CXCL12 chemokine pathway reduces the development of
      murine pulmonary metastases.
AB  - Metastasis continues to be the leading cause of mortality for patients with
      cancer. High expression of the chemokine receptor CXCR4 correlates with poor
      prognosis in many cancers, including osteosarcoma and melanoma. CXCL12, the
      ligand for CXCR4, is expressed at high levels in the lung and lymph node, which
      are the primary sites to which these tumors metastasize respectively. These
      findings suggest that therapy aimed at disruption of this specific
      receptor/ligand complex may lead to a decrease in metastases. CTCE-9908, a small
      peptide CXCR4 antagonist was utilized in two murine metastasis models to test
      this hypothesis. Treatment of osteosarcoma cells in vitro with CTCE-9908 led to
      the following changes: decreased adhesion, decreased migration, decreased
      invasion, and decreased growth rate. Following tail vein injection of
      osteosarcoma cells, mice that were treated with CTCE-9908 had a 50% reduction in
      the number of gross metastatic lung nodules and a marked decrease in micro
      metastatic disease. Similar findings were observed following injection of
      melanoma cells and treatment with CTCE-9908. However, these results could only be
      consistently reproduced when the cells were pre-treated with the inhibitor. A
      novel ex vivo luciferase assay showed decreased numbers of cells in the lung
      immediately after injection into mice, when treated with CTCE-9908, suggesting
      the importance of interactions between the receptor and the ligand. Our findings
      show that inhibition of the CXCR4/CXCL12 pathway decreases metastatic disease in
      two murine tumor models and expands on previous reports to describe potential
      mechanisms of action.

PMID- 18071914
TI  - Cell motility assays.
AB  - This report summarises practical aspects to measuring cell motility in culture.
      The methods described here were discussed at a 1-day European Tissue Culture
      Society (ETCS-UK) workshop organised by John Masters and Gareth E Jones that was
      held at University College London on 19th April 2007.

PMID- 18071916
TI  - A comparative assessment of molecular biological and direct microscopic
      techniques for assessing aquatic systems.
AB  - Molecular techniques have clear value for community characterization; however,
      almost all previous datasets are based upon non-molecular measurements and it is
      hard to compare "old" data with "new" data because few correlations have been
      made. Therefore, the purpose of this evaluation was to simultaneously use
      molecular and non-molecular methods within the same sampling program to determine
      how data compare. Three methods were used for characterizing microbial
      populations in Lake 260 (L260) at Experimental Lakes Area (Ontario, Canada)
      during a whole-lake exposure study. Methods included whole-cell microscopic
      counts (for bacteria, cyanobacteria, algae and zooplankton), chlorophyll a, and
      small sub-unit (ssu)-rRNA hybridization using EUB-338, EUB-785, CYAN-785-a/b,
      EUCA-1379 and UNIV-1390 gene probes. Strong correlations were found between the
      EUB-785 probe signal and "bacteria minus cyanobacteria" direct counts, and the
      EUB-338 probe signal and "bacteria plus cyanobacteria" counts. Furthermore, the
      difference in probe signal between EUB-338 and EUB-785 (a presumptive signature
      for cyanobacteria and plastids) correlated with cyanobacterial direct counts and
      also with chlorophyll a. However, EUCA-1379 probe signal did not correlate with
      algae counts, and UNIV-1390 probe signal only correlated with total bacteria
      counts. Results suggest that, although ssu-rRNA methods are fast, reproducible,
      and specifically detect "viable" organisms, their use may be limited to non
      eukaryotic populations unless new probes are developed that are more specific.

PMID- 18071917
TI  - The impact of vehicular fallout on the Pra estuary of Ghana (a case study of the
      impact of platinum group metals (PGMs) on the marine ecosystem).
AB  - It is increasingly being recognised and environmental measurements have
      demonstrated that Platinum (Pt) (and potentially Rhodium (Rh) and Palladium (Pd))
      is released with the ageing of catalytic converters. Platinum is a particular
      concern as it has a known mutagenic and toxic effect, even at exceedingly low
      concentrations, in urban air (affecting human health) and urban water (affecting
      ecosystem health). In the context given above and given the still keen lack of
      reliable experimental data on the levels of Pd, Pt and Rh in water and sediment,
      this study determined the concentration of such elements in water and sediment of
      the Pra estuary in the Western Region of Ghana where it is estimated that more
      than two thousand cars pass over the bridge under which the river flows to join
      the sea each day. Elevated concentrations of platinum (Pt), palladium (Pd) and
      Rhodium (Rh) were found to be associated with water and soils from areas of high
      traffic densities (Beposo) suggesting that vehicles also contribute heavy metals
      (PGMs) to the environment. The result showed elevated levels of these metals in
      river bank, waterbed and in the water. There is therefore the tendency of
      possible accumulation of these metals in plant and animals along these areas.

PMID- 18071915
TI  - Extracellular ATP is a pro-angiogenic factor for pulmonary artery vasa vasorum
      endothelial cells.
AB  - Expansion of the vasa vasorum network has been observed in a variety of systemic
      and pulmonary vascular diseases. We recently reported that a marked expansion of
      the vasa vasorum network occurs in the pulmonary artery adventitia of chronically
      hypoxic calves. Since hypoxia has been shown to stimulate ATP release from both
      vascular resident as well as circulatory blood cells, these studies were
      undertaken to determine if extracellular ATP exerts angiogenic effects on
      isolated vasa vasorum endothelial cells (VVEC) and/or if it augments the effects
      of other angiogenic factors (VEGF and basic FGF) known to be present in the
      hypoxic microenvironment. We found that extracellular ATP dramatically increases
      DNA synthesis, migration, and rearrangement into tube-like networks on Matrigel
      in VVEC, but not in pulmonary artery (MPAEC) or aortic (AOEC) endothelial cells
      obtained from the same animals. Extracellular ATP potentiated the effects of both
      VEGF and bFGF to stimulate DNA synthesis in VVEC but not in MPAEC and AOEC.
      Analysis of purine and pyrimidine nucleotides revealed that ATP, ADP and MeSADP
      were the most potent in stimulating mitogenic responses in VVEC, indicating the
      involvement of the family of P2Y1-like purinergic receptors. Using
      pharmacological inhibitors, Western blot analysis, and Phosphatidylinositol-3
      kinase (PI3K) in vitro kinase assays, we found that PI3K/Akt/mTOR and ERK1/2 play
      a critical role in mediating the extracellular ATP-induced mitogenic and
      migratory responses in VVEC. However, PI3K/Akt and mTOR/p70S6K do not
      significantly contribute to extracellular ATP-induced tube formation on Matrigel.
      Our studies indicate that VVEC, isolated from the sites of active angiogenesis,
      exhibit distinct functional responses to ATP, compared to endothelial cells
      derived from large pulmonary or systemic vessels. Collectively, our data support
      the idea that extracellular ATP participates in the expansion of the vasa vasorum
      that can be observed in hypoxic conditions.

PMID- 18071918
TI  - Tracking acid mine-drainage in Southeast Arizona using GIS and sediment delivery
      models.
AB  - This study investigates the application of models traditionally used to estimate
      erosion and sediment deposition to assess the potential risk of water quality
      impairment resulting from metal-bearing materials related to mining and
      mineralization. An integrated watershed analysis using Geographic Information
      Systems (GIS) based tools was undertaken to examine erosion and sediment
      transport characteristics within the watersheds. Estimates of stream deposits of
      sediment from mine tailings were related to the chemistry of surface water to
      assess the effectiveness of the methodology to assess the risk of acid mine
      drainage being dispersed downstream of abandoned tailings and waste rock piles. A
      watershed analysis was preformed in the Patagonia Mountains in southeastern
      Arizona which has seen substantial mining and where recent water quality samples
      have reported acidic surface waters. This research demonstrates an improvement of
      the ability to predict streams that are likely to have severely degraded water
      quality as a result of past mining activities.

PMID- 18071919
TI  - Screening and identification of early warning algal species for metal
      contamination in fresh water bodies polluted from point and non-point sources.
AB  - The water bodies of Lucknow, Unnao and Kanpur (U.P.), India polluted through
      various point and non point sources were found to be either eutrophic or
      oligotrophic in nature. These water bodies supported a great number of algal
      diversity, which varied seasonally depending upon the physico-chemical properties
      of water. Further, the water bodies polluted through non point sources supports
      diverse algal species, while the water bodies polluted through point sources
      supports growth of tolerant blue green algae. High biomass producing algal
      species growing in these water bodies have accumulated significant amount of
      metals in their tissues. Maximum amount of Fe was found accumulated by species of
      Oedogonium sp. II (20,523.00 microg g(-1) dw) and Spirogyra sp. I (4,520.00
      microg g(-1) dw), while maximum Chromium (Cr) was found accumulated in Phormedium
      bohneri (2,109.00 microg g(-1) dw) followed by Oscillatoria nigra (1,957.88
      microg g(-1) dw) and Oedogonium sp. I (156.00 microg g(-1) dw) and Ni in Ulothrix
      sp. (495.00 microg g(-1) dw). Results showed that some of these forms growing in
      polluted environment and accumulating high amounts of toxic metals may be used as
      bioindicator species, however, their performance in metal contaminated water
      under different ecological niche is to be ascertained.

PMID- 18071920
TI  - Immunohistochemical study of the pre- and postnatal innervation of the dog lower
      urinary tract: morphological aspects at the basis of the consolidation of the
      micturition reflex.
AB  - Immunohistochemical studies were performed on male and female bladder and urethra
      collected from 4 adults dogs and 10 foetal specimens with crown-rump length from
      53 to 155 mm (medium-sized breeds, presumptive 38 days of gestation to term). A
      panel of antisera was tested, including PGP 9.5 to describe the general
      intramural innervation, ChAT and TH to depict the cholinergic and nor-adrenergic
      components and NOS1, CGRP, SP, NPY, VIP, SOM, GAL, 5-HT to investigate the
      possible nitrergic, peptidergic and aminergic ones. A rich cholinergic
      innervation was present in adult bladder and urethra, along with a lesser number
      of adrenergic nerves and a small number of nitrergic ones. Either bladder or
      urethra received numerous CGRP-, SP-, NPY-, VIP-containing nerve fibres which
      were distributed throughout the muscle layers. All over the lower urinary tract
      strong to weak ChAT-, CGRP-, SP- and NPY-immunoreactivity was detected in
      intramural ganglia, in peripheral nerve bundles and around blood vessels. 5-HT
      immunoreactive endocrine cells were present in the urethral epithelium. Early
      foetal organs were supplied only by cholinergic nerve fibres. Few NOS-, CGRP- and
      SP-ergic components appeared at the end of pregnancy. It can be guessed that
      sensory mediators such as CGRP and SP increase in postnatal ages while other
      neuropeptides, such as NPY and VIP, appear only after birth, as the urinary
      reflex consolidates.

PMID- 18071921
TI  - In vitro reactivity and growth inhibition of EPEC serotype O111 and STEC
      serotypes O111 and O157 by homologous and heterologous chicken egg yolk antibody.
AB  - IgY is a chicken egg yolk antibody which has been used for treatment and
      prophylaxis of gastrointestinal infections. Our aim was to verify if IgY obtained
      from chickens immunized with EPEC O111, STEC O111 and STEC O157 is able to show
      in vitro reactivity and biological activity towards the three bacteria. IgY was
      obtained from eggs laid before and after immunization with each bacterium. The
      preparations of IgY anti-EPEC O111 and anti-STEC O111 shared high reactivity
      detected by ELISA and growth inhibition ability towards both bacteria EPEC O111
      and STEC O111. Nevertheless, the preparation of IgY anti-STEC O157 showed high
      reactivity and growth inhibitory effect only towards the homologous strain. Our
      results showing in vitro biological activity of IgY reinforce its use as an
      alternative for the treatment or prophylaxis of E. coli infections and encourage
      the development of in vivo studies for a possible future human therapeutic use.

PMID- 18071922
TI  - Nocardioides islandiensis sp. nov., isolated from soil in Bigeum Island Korea.
AB  - A novel actinobacterium designated as MSL-26(T) was isolated from soil in Bigeum
      Island Korea. A polyphasic study was undertaken to establish the taxonomic
      position of isolate MSL-26(T). Strain MSL-26(T) was found to have chemical and
      morphological characteristics similar to Nocardioides. The strain grew optimally
      at pH 7.5 and 28 degrees C. Phylogenetic analysis based on 16S rRNA gene
      sequences showed that strain MSL-26(T) forms a distinct line of descent within
      the radiation enclosed by the genus Nocardioides. The cell wall of strain MSL
      26(T) contained LL-2, 6-diaminopimelic acid. The principal menaquinone was MK-8
      (H(4)). The phospholipids detected were diphosphatidylglycerol,
      phosphatidylglycerol and some unidentified lipids. C(18:1) w7c (50.38%) was the
      major fatty acid. The DNA G + C content of strain MSL-26(T) was 71.4 mol%. The
      16S rRNA gene sequence of strain MSL-26(T) shares the highest sequence similarity
      with Nocardioides kribbensis KCTC 19038(T) (95.78%) and Nocardioides aquaticus
      DSM 11439(T) (95.52%). Based on the morphological, physiological, biochemical and
      chemotaxonomical data presented in this study, strain MSL-26(T) should be
      classified as a novel species, for which the name Nocardioides islandiensis sp.
      nov. is proposed. The type strain is MSL-26(T) (=KCTC 19275(T)=DSM 19321(T)).

PMID- 18071923
TI  - Proteomic analysis of highly purified prolamellar bodies reveals their
      significance in chloroplast development.
AB  - The prolamellar body (PLB) proteome of dark-grown wheat leaves was characterized.
      PLBs are formed not only in etioplasts but also in chloroplasts in young
      developing leaves during the night, yet their function is not fully understood.
      Highly purified PLBs were prepared from 7-day-old dark-grown leaves and
      identified by their spectral properties as revealed by low-temperature
      fluorescence spectroscopy. The PLB preparation had no contamination of extra
      plastidal proteins, and only two envelope proteins were found. The PLB proteome
      was analysed by a combination of 1-D SDS-PAGE and nano-LC FTICR MS. The
      identification of chlorophyll synthase in the PLB fraction is the first time this
      enzyme protein was found in extracts of dark-grown plants. This finding is in
      agreement with its previous localization to PLBs using activity studies.
      NADPH:protochlorophyllide oxidoreductase A (PORA), which catalyses the reduction
      of protochlorophyllide to chlorophyllide, dominates the proteome of PLBs. Besides
      the identification of the PORA protein, the PORB protein was identified for the
      first time in dark-grown wheat. Altogether 64 unique proteins, representing
      pigment biosynthesis, photosynthetic light reaction, Calvin cycle proteins,
      chaperones and protein synthesis, were identified. The in number of proteins'
      largest group was the one involved in photosynthetic light reactions. This fact
      strengthens the assumption that the PLB membranes are precursors to the
      thylakoids and used for the formation of the photosynthetic membranes during
      greening. The present work is important to enhance our understanding of the
      significance of PLBs in chloroplast development.

PMID- 18071925
TI  - A generalizability study of the Norwegian version of KINDL in a sample of healthy
      adolescents.
AB  - PURPOSE: The aim in the present study was to illustrate generalizability theory
      by exploring some psychometric aspects of the Norwegian version of KINDL (KINDL
      N). This questionnaire is a measure of quality of life in adolescents. It
      consists of 24 items arranged in six subscales or aspects, corresponding to six
      domains of adolescents' health-related quality of life. METHOD: A total of 239
      healthy adolescents completed the questionnaire. The analysis was performed in
      line with generalization theory, and this analysis yields among other things so
      called generalizability and dependability coefficients, which are analogous to
      reliability coefficients in classical test theory. The preferred design was a
      mixed two-facet design, with the six aspects as a fixed facet and the items
      nested within aspects as a random facet. For comparison, a random two-facet
      design and a one-facet design were also analyzed. RESULTS: The generalizability
      and dependability coefficients for KINDL-N are satisfactory, but the coefficients
      can be markedly improved by increasing the length of the instrument while keeping
      it to a manageable size. The mixed two-facet design resulted in somewhat higher
      coefficients than a one-facet design and much higher coefficients than a random
      two-facet design. CONCLUSION: If the items within a questionnaire are arranged in
      distinct subscales, a two-facet design analyzed by generalizability theory gives
      more sophisticated results than classical test theory. Moreover, the results may
      depend considerably on whether a mixed or random two-facet design is chosen.
      Hence, the choice of an appropriate measurement design in line with the intended
      use of the questionnaire is essential.

PMID- 18071924
TI  - Quality of life and its correlates in octogenarians. Use of the SEIQoL-DW in Wave
      5 of the Aberdeen Birth Cohort 1921 Study (ABC1921).
AB  - BACKGROUND: The direct-weighted Schedule for the Evaluation of Individual Quality
      of Life, Direct Weighting (SEIQoL-DW) is an individualised measure of QoL that
      has been little used in very elderly people. METHODS: We administered SEIQoL-DW
      during Wave 5 of the Aberdeen Birth Cohort 1921 Study (ABC1921) and sought
      statistical correlations with other variables in the data set. ABC1921
      participants had been IQ-tested in 1932 at age 11. Since 1997, data about
      cognition, mental/physical function, personality, health, and socioeconomic
      status have been gathered in five waves of investigations. RESULTS: Ninety-six
      out of 98 individuals, mean age 82.2, completed the SEIQoL-DW. Health, family,
      relationships, finances and social pastimes were the commonest cues nominated,
      but age/gender differences existed. The mean SEIQoL-DW score (74.0) was
      significantly lower than in an approximately 60% sample from Wave 3, the fall
      being greater in men. Variables statistically associated with Wave 5 SEIQoL-DW
      usually reflected current rather than past status [including Short-Form 36 Health
      Survey (SF-36) components and depression], although there were weaker
      correlations with years of education, housing in childhood, conscientiousness,
      and IQ in 1998. CONCLUSIONS: SEIQoL-DW proved feasible and acceptable in
      community-dwelling octogenarians. Recent (i.e. statelike) rather than early or
      long-standing (i.e. traitlike) influences appeared to have the greater effect on
      QoL.

PMID- 18071926
TI  - Handling missing quality of life data in HIV clinical trials: what is practical?
AB  - AIMS: Missing health-related quality of life (HRQOL) data in clinical trials can
      impact conclusions but the effect has not been thoroughly studied in HIV clinical
      trials. Despite repeated recommendations to avoid complete case (CC) analysis and
      last observation carried forward (LOCF), these approaches are commonly used to
      handle missing data. The goal of this investigation is to describe the use of
      different analytic methods under assumptions of missing completely at random
      (MCAR), missing at random (MAR), and missing not at random (MNAR) using HIV as an
      empirical example. METHODS: Medical Outcomes Study HIV (MOS-HIV) Health Survey
      data were combined from two large open-label multinational HIV clinical trials
      comparing treatments A and B over 48 weeks. Inclusion in the HRQOL analysis
      required completion of the MOS-HIV at baseline and at least one follow-up visit
      (weeks 8, 16, 24, 40, 48). Primary outcomes for the analysis were change from
      week 0 to 48 in mental health summary (MHS), physical health summary (PHS), pain
      and health distress scores analyzed using CC, LOCF, generalized estimating
      equations (GEE), direct likelihood and sensitivity analyses using joint mixed
      effects model, and Markov chain Monte Carlo (MCMC) multiple imputation. Time and
      treatment were included in all models. Baseline and longitudinal variables
      (adverse event and reason for discontinuation) were only used in the imputation
      model. RESULTS: A total of 511 patients randomized to treatment A and 473 to
      treatment B completed the MOS-HIV at baseline and at least one follow-up visit.
      At week 48, 71% of patients on treatment A and 31% on treatment B completed the
      MOS-HIV survey. Examining changes within each treatment group, CC and MCMC
      generally produced the largest or most positive changes. The joint model was most
      conservative; direct likelihood and GEE produced intermediate results; LOCF
      showed no consistent trend. There was greater spread for within-group changes
      than between-group differences (within MHS scores for treatment A: -0.1 to 1.6,
      treatment B: 0.4 to 2.0; between groups: -0.7 to 0.4; within PHS scores for
      treatment A: -1.5 to 0.4, treatment B: -1.7 to -0.2; between groups: 0.1 to 1.1).
      The size of within-group changes and between-group differences was of similar
      magnitude for the pain and health distress scores. In all cases, the range of
      estimates was small <0.2 SD (less than 2 points for the summary scores and 5
      points for the subscale scores). CONCLUSIONS: Use of the recommended likelihood
      based models that do not require assumptions of MCAR was very feasible.
      Sensitivity analyses using auxiliary information can help to investigate the
      potential effect that missing data have on results but require planning to ensure
      that relevant data are prospectively collected.

PMID- 18071927
TI  - The evaluation of protein structure prediction results.
AB  - Methods for protein structure prediction are flourishing and becoming widely
      available to both experimentalists and computational biologists. However, how
      good are they? What is their range of applicability and how can we know which
      method is better suited for the task at hand? These are the questions that this
      review tries to address, by describing the worldwide Critical Assessment of
      techniques for protein Structure Prediction (CASP) initiative and focusing on the
      specific problems of assessing the quality of a protein 3D model.

PMID- 18071928
TI  - Clinical significance of serum MMP-2 and MMP-7 in patients with ovarian cancer.
AB  - Matrix metalloproteinases (MMPs) are frequently expressed in malignant tumors and
      play an important role in tumor invasion and metastasis. The aim of this study
      was to evaluate role of serum MMP-2 and MMP-7 levels in patients with ovarian
      cancer. Serum levels of MMP-2 and MMP-7 were measured in 28 patients with ovarian
      carcinoma, 2 with borderline ovarian tumors, 10 with non-malignant gynecological
      disease and 30 healthy women by Enzyme-Linked Immunosorbent Assay (ELISA). Serum
      MMP-7 level was significantly (10.24+/-1.35 ng/ml) higher in the patients with
      ovarian malign tumors than healthy controls (3.29+/-1.64 ng/ml) (P<0.05).
      Postoperative levels of MMP-7 (7.68+/-1.17 ng/ml) were significantly lower in
      patients with malign ovarian tumors than those of preoperative level (10.24+/
      1.35 ng/ml) (P<0.05). Serum MMP-2 levels were significantly lower in the patients
      with ovarian malign tumors (227.51+/-9.91 ng/ml) than those in the healthy
      controls (279.12+/-73 ng/ml) (P<0.05). There was no significant difference in
      serum levels of MMP-2 and MMP-7 in patients with benign ovarian disease when
      compared to healthy controls and patients with malignant disease (P>0.05). As a
      conclusion, MMP-7 can be a useful serum marker to show disease activity in
      malignant ovarian tumors.

PMID- 18071929
TI  - [Pectoralis major transfer in the treatment of chronic subscapularis
      insufficiency].
AB  - OBJECTIVE: Pain-free movement and stability of the shoulder joint after
      restoration of muscular balance between the internal and external rotators.
      Eradication of anterior impingement. INDICATIONS: Irreparable rupture of the
      subscapularis tendon in active patients. CONTRAINDICATIONS: Less active patients
      who are older than about 60 years. Concomitant infraspinatus tendon rupture.
      Frozen shoulder. Rotator cuff arthropathy. SURGICAL TECHNIQUE: General anesthetic
      and beach-chair position with the arm freely mobile. Deltopectoral approach.
      Exposure of the lesser tubercle and the conjoined tendon of coracobrachialis and
      the short head of the biceps. Half to two thirds of the insertion of pectoralis
      major at the humeral shaft are detached proximally, held in a suture loop, and
      passed under the conjoined tendon. The tendon is then fixed transosseously to the
      lesser tubercle, and range of motion is evaluated. External rotation of up to 30
      degrees without tension must be confirmed. POSTOPERATIVE MANAGEMENT: A shoulder
      strap is worn for 6 weeks and passive physiotherapy is commenced on day 2
      postoperatively. External rotation can only be practiced after week 7. RESULTS:
      23 patients were available to follow-up. There were 13 cases of anterosuperior
      defect with irreparable supraspinatus tendon. The preoperative Constant Score of
      35 points improved to a postoperative score of 68 points. It was not possible to
      restore powerful internal rotation. Preoperative impingement syndrome was
      eradicated.

PMID- 18071930
TI  - Total hip replacement through a minimally invasive, anterolateral approach with
      the patient supine.
AB  - OBJECTIVE: Early postoperative mobilization and restoration of pain-free joint
      function by implantation of a total hip replacement through a standardized,
      minimally invasive approach regardless of the type of implant with the patient in
      the supine position. INDICATIONS: Primary and secondary coxarthrosis. Femoral
      head necrosis. CONTRAINDICATIONS: Previously operated patients with deformities
      of the coxal end of the femur and extensive scarring. SURGICAL TECHNIQUE: Supine
      position. Skin incision anterior to the greater trochanter at the level of the
      interval between the tensor fasciae latae muscle and the iliotibial tract
      parallel to the acetabulum ascending slightly from distal to proximal. Incision
      of the iliotibial tract posterior to the interval. Coagulation of intersecting
      vessels. Blunt dissection to the femoral neck anterior to the gluteal muscles. L
      shaped incision of the anterior capsule with the base at the lateral femoral
      neck. Femoral neck osteotomy and resection of the femoral head. Mobilization of
      the posterior capsule by incision at the junction with the femur. Insertion of
      Hohmann elevators to protect the tissue, dissection of the acetabulum and
      implantation of the acetabular component. In adduction, external rotation and
      hyperextension, dissection of the coxal end of the femur, and implantation of the
      prosthetic stem. After reduction, adaptive suture of the cranial capsular parts.
      Insertion of intraarticular Redon drains. Interrupted suture of the iliotibial
      tract. Subcutaneous Redon drains. Subcutaneous suture. Skin suture. Sterile
      dressing. Final radiologic evaluation in anteroposterior view. POSTOPERATIVE
      MANAGEMENT: Mobilization from postoperative day 1. Increased loading on the
      operated leg depending on local pain. Four-point gait from day 2-3. Stair
      climbing from day 4. RESULTS: From September 2004 to July 2006, 195 patients were
      operated on (105 women, 90 men, average age 64.4 years [37.1-88.4 years]).
      Average operating time 63 min (35-105 min). Average intraoperative blood loss 437
      ml (20-800 ml). Postoperative follow-up of all patients at 3, 6, and 12 months,
      and then annually. Early restoration of full weight-bearing ability and range of
      motion within the first few weeks. COMPLICATIONS: two postoperative
      periprosthetic fractures. No periarticular ossifications > Brooker II. No
      hematoma requiring revision. No neurologic deficits.

PMID- 18071931
TI  - [Implantation technique for the CUT-type femoral neck endoprosthesis].
AB  - OBJECTIVE: Total hip replacement with maximum preservation of femoral neck.
      Restoration of pain-free joint function. INDICATIONS: Coxarthrosis, femoral head
      necrosis in younger patients with intact femoral neck. CONTRAINDICATIONS: Joint
      infection. Coxa valga (caput-collum-diaphysis [CCD] angle > 150 degrees ). Coxa
      vara (CCD angle < 110 degrees ). Body mass index > 30 (relative
      contraindication). Ongoing chemotherapy. Osteoporosis. SURGICAL TECHNIQUE:
      Transgluteal or anterolateral approach. Resection of two thirds of the femoral
      head. Implantation of uncemented acetabular component. Revitalization of the
      femoral neck with special rasps for the CUT prosthesis. Trial reduction with bone
      rasp and modular cone in place (10 degrees or 20 degrees angle). Uncemented stem
      implantation. RESULTS: From 2002 to 2006, 49 uncemented CUT prostheses were
      implanted in 36 patients. Average age was 45.1 years (20-60 years). Inpatient
      stay amounted to 10.8 days and operating time to 74 min. Average blood loss
      through drainage was 795 ml, an average of 297 ml transfused back. Transfusion
      was necessary in ten patients. There were no cases of postoperative infection,
      nerve lesion, or hip dislocation. Patients were examined preoperatively and
      followed up at 6 weeks and 1 year. Harris Hip Score improved from 46.1 points
      preoperatively to 81.6 points at 6 weeks and 95.7 points at 1 year. Average leg
      length discrepancy of 0.7 cm (minimum -0.8, maximum 2.2 cm) was determined
      radiologically in 31 of 49 patients. It became necessary to replace two of the 49
      stems due to aseptic loosening, in the first case at 19 months (femoral head
      osteonecrosis, lupus erythematosus, and taking cortisone), and in the second case
      3 years after implantation (steroid-induced femoral head necrosis related to
      Crohn's disease and azathioprine [Imurek] therapy). One cone and head component
      had to be revised 1 month after implantation due to impingement syndrome. One
      ceramic head fractured 2.5 years after implantation so that cone and head
      required revision. The overall follow-up time was 37 months on average (minimum
      12, maximum 55 months).

PMID- 18071932
TI  - [Double-bundle technique - anatomic reconstruction of the anterior cruciate
      ligament].
AB  - OBJECTIVE: To improve the rotational stability of the knee by anatomic
      reconstruction of the anterior cruciate ligament by socalled double-bundle
      technique using anteromedial and posterolateral grafts from native semitendinosus
      and gracilis. The grafts are fixed with bioabsorbable screws utilizing aperture
      fixation. INDICATIONS: Complete tear of the anterior cruciate ligament with
      positive Lachman sign and pivot shift. CONTRAINDICATIONS: Open growth plate.
      Osteoarthritis > grade 1 according to Jager & Wirth. Age > or = 50 years with low
      sports activity (relative contraindication). SURGICAL TECHNIQUE: Graft harvest of
      the semitendinosus and gracilis tendons via a 3-cm horizontal skin incision
      parallel to pes anserinus and preparation of the tendons as double-looped grafts.
      Arthroscopy, resection of the stump of the anterior cruciate ligament, and
      clearance of its origin and insertion. Tunnel placement by means of aiming
      devices in the following order: tibial posterolateral, tibial anteromedial,
      femoral anteromedial (transtibial or via the anteromedial portal in 120 degrees
      flexion), and femoral posterolateral (via additional medial arthroscopic portal).
      The anteromedial (semitendinosus tendon) and posterolateral (gracilis tendon)
      bundles are passed through the tunnels and fixed on the femoral side. Tibial
      fixation of the graft by bioresorbable interference screw with knee flexion of 45
      degrees (anteromedial) and 10 degrees (posterolateral). POSTOPERATIVE MANAGEMENT:
      Depending on the degree of swelling, rehabilitation with partial weight bearing
      for 14 days and full range of motion. Return to sports after 6 months, no contact
      sports until 9 months. RESULTS: From May 2004 to June 2005, anatomic double
      bundle reconstruction was performed in 19 patients (13 male, six female, average
      age 31 years [18-48 years]) with isolated anterior cruciate ligament rupture
      without concomitant lesions. Clinical follow-up examination on average at 21.3
      months (16-30 months) postoperatively. The Lysholm Score improved from an average
      of 65.2 to 94.5 points (75-100 points). The IKDC (International Knee
      Documentation Committee) Score yielded nine very good and ten good results in the
      relevant subgroups of motion, effusion and ligament stability. Measurement of
      anteroposterior translation with the KT-1000 instrument at 134 N showed increased
      translation of 1.8 mm (-2 to 5 mm) compared to the contralateral knee.

PMID- 18071933
TI  - [Reconstruction of the medial patellofemoral ligament by tunnel transfer of the
      semitendinosus tendon].
AB  - OBJECTIVE: Stabilization of the patella by reconstruction of the medial
      patellofemoral ligament. INDICATIONS: Chronic recurrent lateral dislocation or
      subluxation of the patella. Habitual lateral dislocation of the patella.
      CONTRAINDICATIONS: Primary dislocation of the patella. Genu valgum with a Q-angle
      > 15 degrees . Status following semitendinosus tendon transfer to reconstruct the
      anterior cruciate ligament. Joint infection. Neurogenic instability, ischiocrural
      muscle deficiency. SURGICAL TECHNIQUE: Division of the distal insertion of the
      semitendinosus muscle at the pes anserinus. Subligamentous tunneling at the
      proximal insertion of the medial collateral ligament. The distal end of the
      semitendinosus tendon is transferred through the subligamentous tunnel to the
      medial patellar margin. Fixation of the tendon to the medioproximal patellar
      margin by passing it through an oblique transpatellar drill hole. RESULTS: The
      patella was stabilized by dynamic reconstruction of the medial patellofemoral
      ligament in 14 patients with chronic recurrent or habitual lateral patellar
      dislocation. Ten patients were available for clinical follow-up assessment at an
      average of 13 months (8-27 months) postoperatively. The postoperative Kujala
      Index (maximum 100 points) increased on average from 56 to 95 points.

PMID- 18071934
TI  - [Surgery for superficial peroneal nerve entrapment syndrome].
AB  - OBJECTIVE: Relief of chronic pain over the lateral aspect of the leg through
      decompression of the superficial peroneal nerve where it emerges from the deep
      fascia of the leg. INDICATIONS: Chronic pain over the lateral side (lower
      quarter) of the leg and the dorsum of the ankle exaggerated by activities of
      daily living and sports; sometimes sensory abnormality or decreased sensibility
      in the distribution of the nerve over the dorsum of the foot. Presence of a
      positive Tinel-Hoffmann sign at the site of compression. CONTRAINDICATIONS:
      Occasional pain or absence of chronic pain. SURGICAL TECHNIQUE: Before starting
      spinal anesthesia, the site of nerve compression has to be identified (Tinel
      Hoffmann sign) and marked. Supine position, internal rotation of the affected
      leg. Thigh tourniquet. Longitudinal skin incision over the lateral aspect of the
      leg 1 cm posterior to the site of compression. The nerve is released by local
      fasciotomy where it emerges through the deep fascia. Release of the tourniquet
      and careful hemostasis. No suture of the fascia. Subcutaneous and skin suture.
      Sterile compressive dressing. RESULTS: Between November 1998 and April 2003, a
      decompression of the superficial peroneal nerve was performed in twelve legs of
      twelve patients (seven men and five women, average age 40 years [18-50 years]).
      Follow-up after an average of 48 months (12-84 months) based on subjective and
      clinical evaluation. The clinical examination consisted of the search for Tinel
      Hoffmann sign and subjective assessment on a questionnaire. Postoperatively, at
      clinical examination no entrapment sign was found in any patient. The subjective
      rating was excellent in eight patients and good in four. It had always improved
      when compared with the preoperative situation. All patients would accept the
      surgery again for an identical condition.

PMID- 18071935
TI  - [Supramalleolar, subtractive valgus osteotomy of the tibia in the management of
      ankle joint degeneration with varus deformity].
AB  - OBJECTIVE: The aim of supramalleolar osteotomy of the tibia in the management of
      varus deformity of the upper ankle joint is to shift load bearing away from the
      severely degenerated medial part of the joint to the lateral part and thus
      restore physiological alignment of the hindfoot and a plantigrade foot. The
      intention is to reduce pain and to postpone the need for total endoprosthesis or
      arthrodesis. INDICATIONS: Painful degeneration of the ankle joint with varus
      deformity that has proven resistant to conservative treatment, i.e., > 15 degrees
      axial malalignment of the tibiotalar joint axis. CONTRAINDICATIONS: Severe ankle
      joint degeneration that restricts movement. Florid infections. Extensive bone and
      soft-tissue defects. Osteonecrosis of the talus with necrotic regions > 50%.
      SURGICAL TECHNIQUE: Anterior approach to the upper ankle joint and supramalleolar
      wedge-shaped resection of a predetermined bone wedge with lateral base. The
      desired correction is precisely calculated during preoperative planning.
      Subsequently, lateral approach over the distal fibula. Resection of a more
      proximal segment from the fibula. Closure of the tibial osteotomy (closed wedge)
      and osteosynthesis of the fibula. RESULTS: A supramalleolar valgus osteotomy
      (closed wedge) was performed in 27 patients from 2002 to 2006. Preoperatively,
      there was an average varus deformity of 27 degrees , which was corrected to 6
      degrees on average postoperatively. 21 patients were very satisfied at follow-up,
      three patients required joint replacement during the later course, and another
      three patients needed arthrodesis.

PMID- 18071936
TI  - [Management of posttraumatic osteoarthritis of the upper ankle joint by
      implantation of the S.T.A.R. ankle prosthesis].
AB  - OBJECTIVE: Treatment of posttraumatic osteoarthritis of the upper ankle joint by
      implantation of an uncemented total ankle joint prosthesis. INDICATIONS: Painful
      osteoarthritis of any kind affecting the upper ankle joint with adequate joint
      stability, without significant bone deformity of the ankle axes (deviation of the
      lower leg axis in the distal third in the horizontal and sagittal planes < or =
      20 degrees ), without manifest osteoporosis, with normal peripheral vascularity,
      correct alignment of the hindfoot, minimal sports expectations on the part of the
      patient, and good residual range of motion. CONTRAINDICATIONS: Avascular talus
      necrosis > or = 25%. Degenerative neuropathic joint disease (Charcot's joint).
      Acute or chronic ankle joint infection. Sensory or motor dysfunction of the foot.
      Preceding arthrodesis of the ankle with resection of the malleoli. Medial
      instability of the upper ankle joint. Tibiotalar varus or valgus deformity > 20
      degrees . SURGICAL TECHNIQUE: Anterior approach to the upper ankle joint.
      Resection of the distal tibial joint surface and the cranial talar surface
      including the sides of the talus. Uncemented implantation of the talar cap, and
      the tibial component. Insertion of a polyethylene sliding core. RESULTS: From
      January 2004 to March 2005, 13 patients with posttraumatic osteoarthritis were
      treated by implantation of an uncemented S.T.A.R. ankle prosthesis (Scandinavian
      Total Ankle Replacement). The indication for total joint replacement in all cases
      was advanced osteoarthritis of the upper ankle joint that could no longer be
      managed by conservative treatment. In one patient, the medial malleolus fractured
      intraoperatively and had to be stabilized with a screw. There was neither deep
      nor superficial infection. One patient developed persistent chronic regional pain
      syndrome without radiologic evidence. After an average follow-up period of 6.8
      months (3-12 months), the range of motion had improved in all patients from 10-0
      20 degrees to 15-0-30 degrees on average. The AOFAS (American Orthopaedic Foot
      and Ankle Society) Hindfoot Score improved from 53 to 89 points.

PMID- 18071937
TI  - [Ankle arthrodesis with interposition graft as a salvage procedure after failed
      total ankle replacement].
AB  - OBJECTIVE: Restoration of painless function to the lower limb by ankle fusion
      after failure of total ankle arthroplasty. INDICATIONS: Loose total ankle
      replacement. Severe ankle destruction and axial deviation in rheumatoid patients.
      Severe osteoarthritis in the subtalar and ankle joints. CONTRAINDICATIONS:
      Infected total ankle replacement. Severe arterial occlusive disease of the
      affected extremity. SURGICAL TECHNIQUE: Transfibular approach to the subtalar and
      ankle joints. Osteotomy and resection of the distal fibula 7-8 cm proximal to the
      tip of the lateral malleolus. Removal of the prosthetic components, synovectomy,
      and revitalization of the remaining bone surface. Removal of any residual
      articular cartilage from the subtalar joint surfaces. Determination of the extent
      of bone loss and defect filling with horizontally or vertically placed
      tricortical and cancellous bone graft from the resected fibula and, if necessary,
      from the ipsilateral anterior iliac crest. Tibiotalocalcaneal arthrodesis by
      retrograde insertion of a retrograde locking nail. Wound closure in layers. Split
      below-knee cast. POSTOPERATIVE MANAGEMENT: Mobilization with below-knee cast
      without weight bearing for 6 weeks. Dynamic locking of the intramedullary nail.
      Partial weight bearing with a walker up to 20 kg for an additional 6 weeks.
      Gradual increase in weight bearing in accordance with radiologic evidence of
      consolidation. Fitted orthopedic shoe with rocker-bottom sole, and made to
      measure insoles. RESULTS: From January 2003 to September 2006, 15 patients with
      infected ankle prosthesis loosening (six Thompson-Richards prostheses, eight
      S.T.A.R. prostheses, and one Salto prosthesis) were treated. All patients
      underwent tibiotalocalcaneal interposition arthrodesis with femoral nailing in
      retrograde technique. The average AOFAS (American Orthopaedic Foot and Ankle
      Society) Score was 57.9 points (35-81 points) postoperatively. One patient
      developed a nonunion and revision surgery will have to be performed. Another
      patient with delayed wound healing and skin necrosis needed plastic surgery.

PMID- 18071938
TI  - [Reconstruction of the lateral tibial head by patellar transplantation].
AB  - OBJECTIVE: Restoration of the lateral tibial condyle, a functionally intact knee
      joint, and correct physiological axis. INDICATIONS: Posttraumatic cartilage and
      bone defect of the lateral tibial condyle too severe for reconstruction in a
      young patient. CONTRAINDICATIONS: Age > 50 years. Patellofemoral joint
      degeneration. Defect of the patella or lateral femoral condyle. SURGICAL
      TECHNIQUE: Transplantation of the own, ipsilateral patella into the bone defect
      of the lateral tibial condyle. RESULTS: The result in one patient was found to be
      excellent 5 years after the accident and was good in one other patient 13 years
      following trauma. The third patient showed a good result 1.5 years after the
      accident.

PMID- 18071939
TI  - Historical development of monoclonal antibody therapeutics.
AB  - Since the first publication by Kohler and Milstein on the production of mouse
      monoclonal antibodies (mAbs) by hybridoma technology, mAbs have had a profound
      impact on medicine by providing an almost limitless source of therapeutic and
      diagnostic reagents. Therapeutic use of mAbs has become a major part of
      treatments in various diseases including transplantation, oncology, autoimmune,
      cardiovascular, and infectious diseases. The limitation of murine mAbs due to
      immunogenicity was overcome by replacement of the murine sequences with their
      human counterpart leading to the development of chimeric, humanized, and human
      therapeutic antibodies. Remarkable progress has also been made following the
      development of the display technologies, enabling of engineering antibodies with
      modified properties such as molecular size, affinity, specificity, and valency.
      Moreover, antibody engineering technologies are constantly advancing to enable
      further tuning of the effector function and serum half life. Optimal delivery to
      the target tissue still remains to be addressed to avoid unwanted side effects as
      a result of systemic treatment while achieving meaningful therapeutic effect.

PMID- 18071940
TI  - Preclinical safety evaluation of monoclonal antibodies.
AB  - Monoclonal antibodies (mAbs) are a well-established product class of
      biotechnology-derived pharmaceuticals for treating multiple diseases. A growing
      number of mAbs are being tested in clinical trials worldwide. Many of the second
      generation mAbs entering the clinic today are highly engineered, produced from
      recombinant cell lines, and present new safety challenges for regulators and
      industry scientists responsible for their safety evaluation. The increasing
      complexity of antibodies and the variety of recombinant production cell systems
      used for antibody manufacturing require a well thought-out approach for
      preclinical safety evaluation of mAbs. The focus of this chapter is to provide
      the reader with a basic framework for preparing a scientifically sound
      preclinical package for safety evaluation of therapeutic mAbs. We outline the
      general considerations for planning a preclinical program and the issues critical
      for success. We describe the types of preclinical safety studies and the timing
      for their conduct in relation to clinical trials. We also share some of the
      lessons learned about toxicity of mAbs from previous antibody development
      programs. A list of relevant regulatory documents issued by various government
      agencies and selected references to other useful texts and publications are also
      provided in the chapter. We believe that applying the principles described in
      this chapter will improve the quality and relevance of the preclinical safety
      data generated to support the future development of mAbs therapeutics.

PMID- 18071941
TI  - Engineering antibodies for stability and efficient folding.
AB  - Antibody variable domains vary widely in their intrinsic thermodynamic stability.
      Despite the mutual stabilization of the domains in the scFv fragment, most scFv
      derived from monoclonal antibodies without further engineering show poor to
      moderate stability. The situation gets more complex for Fab fragments and full
      sized antibodies: while the disulfide-linked C(L)/C(H) heterodimer shows very
      limited thermodynamic stability, its unfolding kinetics are very slow. The same
      is true for Fab fragments, which, due to this kinetic stabilization, appear to be
      more stable than their thermodynamic stability suggests. However, suboptimal
      variable domains can be engineered for improved stability and folding efficiency
      while preserving their antigen-binding specificity and affinity, either by a
      limited number of point mutations or by grafting their antigen specificity to
      superior variable domain frameworks.

PMID- 18071942
TI  - Human monoclonal antibodies from transgenic mice.
AB  - Since the 1986 regulatory approval of muromonomab-CD3, a mouse monoclonal
      antibody (MAb) directed against the T cell CD3epsilon antigen, MAbs have become
      an increasingly important class of therapeutic compounds in a variety of disease
      areas ranging from cancer and autoimmune indications to infectious and cardiac
      diseases. However, the pathway to the present acceptance of therapeutic MAbs
      within the pharmaceutical industry has not been smooth. A major hurdle for
      antibody therapeutics has been the inherent immunogenicity of the most readily
      available MAbs, those derived from rodents. A variety of technologies have been
      successfully employed to engineer MAbs with reduced immunogenicity.
      Implementation of these antibody engineering technologies involves in vitro
      optimization of lead molecules to generate a clinical candidate. An alternative
      technology, involving the engineering of strains of mice to produce human instead
      of mouse antibodies, has been emerging and evolving for the past two decades.
      Now, with the 2006 US regulatory approval of panitumumab, a fully human antibody
      directed against the epidermal growth factor receptor, transgenic mice expressing
      human antibody repertoires join chimerization, CDR grafting, and phage display
      technologies, as a commercially validated antibody drug discovery platform. With
      dozens of additional transgenic mouse-derived human MAbs now in clinical
      development, this new drug discovery platform appears to be firmly established
      within the pharmaceutical industry.

PMID- 18071943
TI  - Anti-TNF antibodies: lessons from the past, roadmap for the future.
AB  - Tumor necrosis factor alpha (TNF) is an important cell-signaling component of the
      immune system. Since its discovery over 20 years ago, much has been learned about
      its functions under normal and disease conditions. Nonclinical studies suggested
      a role for TNF in chronic immune-mediated inflammatory diseases, such as
      rheumatoid arthritis, Crohn's disease, and psoriasis, and therefore neutralizing
      monoclonal antibodies specific to human TNF were developed for clinical
      evaluation. Treatment with anti-TNF monoclonal antibodies (infliximab,
      adalimumab, and certolizumab pegol) has been shown to provide substantial benefit
      to patients through reductions in both localized and systemic expression of
      markers associated with inflammation. In addition, there are beneficial effects
      of anti-TNF treatment on markers of bone and cartilage turnover. Further
      exploration of changes in these markers and their correlation with clinical
      measures of efficacy will be required to allow accurate prediction of those
      patients most in need of these treatments. Both the clinical and commercial
      experience with these anti-TNF antibodies provide a wealth of information
      regarding their pharmacological effects in humans.

PMID- 18071944
TI  - Therapeutic anti-VEGF antibodies.
AB  - Vascular endothelial growth factor (VEGF-A) is a key cytokine in the development
      of normal blood vessels as well as the development of vessels in tumors and other
      tissues undergoing abnormal angiogenesis. Here, we review the molecular
      engineering of two humanized antibodies derived from a common mouse anti-VEGF
      antibody--bevacizumab, a full-length IgG1 approved for the treatment of specified
      cancer indications, and ranibizumab, an affinity-matured antibody Fab domain
      approved for use in age-related macular degeneration (AMD). In clinical trials
      and as FDA-approved therapeutics, these two anti-VEGF antibodies, bevacizumab
      (Avastin anti-VEGF antibody) and ranibizumab (Lucentis anti-VEGF antibody), have
      demonstrated therapeutic utility in blocking VEGF-induced angiogenesis.

PMID- 18071945
TI  - Humanized antihuman IL-6 receptor antibody, tocilizumab.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates immune responses
      and inflammatory reactions. Overproduction of IL-6 has been shown to play a role
      in inflammatory autoimmune diseases such as rheumatoid arthritis (RA), and
      juvenile idiopathic arthritis (JIA) and, therefore, an agent blocking IL-6
      actions can be a therapy of these diseases. IL-6 belongs to a cytokine family,
      which shares the cytokine receptor subunit glycoprotein (gp) 130. This family
      also includes IL-11, oncostatin-M, and leukemia inhibitory factor (LIF). In the
      IL-6 receptor (IL-6R) system, both a membrane-bound IL-6R and a soluble form of
      IL-6R are able to mediate IL-6 signals into the cells through the interaction of
      gp130. Tocilizumab is a humanized antihuman IL-6 receptor antibody designed using
      genetic engineering technology. Tocilizumab recognizes both the membrane-bound
      and the soluble form IL-6R and specifically blocks IL-6 actions. Tocilizumab is
      expected to ameliorate the autoimmune inflammatory diseases with IL-6
      overproduction and has been clinically developed as a therapeutic agent for RA,
      systemic-onset and articular types of JIA, Crohn's disease, etc. Tocilizumab has
      been shown to be effective not only for improving signs and symptoms but also for
      preventing joint destruction of RA. Immunopharmacology and clinical benefit of
      tocilizumab in RA is addressed.

PMID- 18071946
TI  - Anti-CD20 monoclonal antibody in rheumatoid arthritis and systemic lupus
      erythematosus.
AB  - Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are both chronic
      autoimmune rheumatic diseases. In the last few years, evolution in the
      understanding of RA and SLE pathogenesis and underlying molecular mechanisms has
      resulted in development and availability of novel therapies. In particular, the
      recent acknowledgement of a more significant role for B cells in the pathogenesis
      of RA, in contrast to the view that it was predominantly a T cell disorder,
      provided rationale for trials of B cell depletion therapy with the chimeric anti
      CD20 monoclonal antibody rituximab. The efficacy and favourable safety profile of
      rituximab have resulted in the recent approval by the European Medicines Agency
      for its usage in patients with RA unresponsive to conventional therapies. The
      salient features from the pivotal open and randomised controlled trials are
      reviewed in this chapter. Given the recognition of B cell dysfunction as central
      to SLE pathogenesis, the use of anti-CD20 antibody therapy for this patient group
      has also been established. Results of the open trials have been encouraging,
      particularly in patients not responding to usual therapies, and a randomised
      controlled trial is underway.

PMID- 18071947
TI  - Herceptin.
AB  - The biology of the human epidermal growth factor (EGF) receptor-2 (HER2) has been
      reviewed numerous times and provides an excellent example for developing a
      targeted cancer therapeutic. Herceptin, the FDA-approved therapeutic monoclonal
      antibody against HER2, has been used to treat over 150,000 women with breast
      cancer. However, the developmental history of Herceptin, the key events within
      the program that created pivotal decision points, and the reasons why decisions
      were made to pursue the monoclonal antibody approach have never been adequately
      described. The history of Herceptin is reviewed in a way which allows the
      experience to be shared for the purposes of understanding the drug discovery and
      development process. It is the objective of this review to describe the pivotal
      events and explain why critical decisions were made that resulted in the first
      therapeutic to successfully target tyrosine kinases in cancer. New approaches and
      future prospects for therapeutics targeting the HER family are also discussed.

PMID- 18071948
TI  - The use of CD3-specific antibodies in autoimmune diabetes: a step toward the
      induction of immune tolerance in the clinic.
AB  - CD3-specific monoclonal antibodies were the first rodent monoclonals introduced
      in clinical practice in the mid 1980s as approved immunosuppressants to prevent
      and treat organ allograft rejection. Since then compelling evidence has been
      accumulated to suggest that in addition to their immunosuppressive properties,
      CD3-specific antibodies can also afford inducing immune tolerance especially in
      the context of ongoing immune responses. Thus, they are highly effective at
      restoring self-tolerance in overt autoimmunity, a capacity first demonstrated in
      the experimental setting, which was recently transferred to the clinic with
      success.

PMID- 18071949
TI  - Monoclonal antibody therapy for prostate cancer.
AB  - Early detection of prostate cancer (PCa) and advances in hormonal and
      chemotherapy treatments have provided great clinical benefits to patients with
      early stages of the disease. However, a significant proportion of patients still
      progress to advanced, metastatic disease, for which no effective therapies are
      available. Therefore, there is a critical need for new treatment modalities,
      ideally targeted specifically to prostate cancer cells. The recent clinical and
      commercial successes of monoclonal antibodies (MAbs) have made them the most
      rapidly expanding class of therapeutics being developed for many disease
      indications, including cancer. PCa is well suited for antibody-based therapy due
      to the size and location of recurrent and metastatic tumors, and the lack of
      necessity to avoid targeting the normal prostate, a nonessential organ. These
      properties have fostered interest in the development and clinical evaluation of
      therapeutic MAbs directed to both well established and newly discovered targets
      in PCa. MAbs directed to established targets include those approved for other
      solid tumors, including anti-human epidermal growth factor receptor-2 (HER2) MAb
      trastuzumab, anti-epidermal growth factor receptor (EGFR) MAbs cetuximab and
      panitumumab, and the antivascular endothelial growth factor (VEGF) MAb
      bevacizumab. Genomics efforts have yielded a large number of novel, clinically
      relevant targets in PCa with the desirable expression profiling in tumor and
      normal tissues, and with an implicated role in tumor growth and spread. Growing
      efforts are directed to the development of naked or payload-conjugated
      therapeutic antibodies to these targets, and a variety of MAb products are
      currently progressing through preclinical and various stages of clinical
      development. The clinical experience with some of the commercialized MAb products
      points out specific challenges in conducting clinical trials with targeted
      therapy in PCa.

PMID- 18071950
TI  - Anti-IgE and other antibody targets in asthma.
AB  - Asthma is a heterogeneous disorder of unknown etiology that manifests as
      recurrent episodes of coughing, wheezing, and breathlessness. These symptoms are
      often debilitating and exacerbations usually are unexpected, resulting in work or
      school absences, limitations in activity, reduced quality of life, and personal
      and economic hardships. Over the past several decades, a great deal has been
      learned about asthma pathophysiology, and currently available therapies have
      revolutionized asthma treatment. However, asthma remains a global public health
      problem, and the hope is that newer therapies targeting specific biological
      mediators of asthma, particularly antibody-mediated therapies, offer exciting new
      modes to the control of this disease. We will review some of these therapies,
      with the majority of attention devoted to anti-IgE therapy which has been
      approved for treatment of adult and childhood asthma by the US Food and Drug
      Administration (FDA) since 2003.

PMID- 18071951
TI  - Cytokine, chemokine, and co-stimulatory fusion proteins for the immunotherapy of
      solid tumors.
AB  - This chapter describes the generation of novel reagents for the treatment of
      cancer using fusion proteins constructed with natural ligands of the immune
      system. Immunotherapy is a powerful therapeutic modality that has not been fully
      harnessed for the treatment of cancer. We and others have hypothesized that if
      the proper immunoregulatory ligands can be targeted to the tumor, an effective
      immune response can be mounted to treat both established primary tumors and
      distant metastatic lesions. Though it is generally believed that immunotherapy
      has the potential to treat only residual disease, we offer evidence that this
      approach can, by itself, destroy large tumor masses and produce lasting
      remissions of experimental solid tumors. From these studies, three major classes
      of immune activators, namely, cytokines, chemokines, and costimulatory molecules,
      have been shown to generate antitumor responses in animal models. In addition,
      the reversal of immune tolerance by the deletion of T regulatory (Treg) cells has
      been shown to be equally important for effective immunotherapy. In an attempt to
      identify reagents that can provide an enhanced immune stimulation and treatment
      of cancer, our laboratory has developed a novel monoclonal antibody targeting
      approach, designated Tumor Necrosis Therapy (TNT), which utilizes stable
      intracellular antigens present in all cell types but which are only accessible in
      dead and/or dying cells. Since tumors contain necrotic and degenerating regions
      that account for 30-80% of the tumor mass, this targeting approach can be used to
      deliver therapeutic reagents to the core of tumors, a site abundant in tumor
      antigens. In our first set of reagents, a panel of cytokine fusion proteins was
      genetically engineered using monoclonal antibody chimeric TNT-3 (chTNT-3)
      directed against necrotic regions of tumors (single-stranded DNA) fused with IL
      2, or GM-CSF, or TNFalphaa, or IFNgamma. Tested against different solid tumors,
      these reagents were found to mount an effective although transient immune
      response to tumor especially when used in combination. To improve upon these
      results, additional chTNT-3 fusion proteins using the liver-expression chemokine
      (LEC) and the costimulatory molecule B7.1 were constructed. Both of these
      reagents were found to work significantly better than the above cytokine fusion
      proteins due to their ability to stimulate multiple arms of the immune system
      deemed useful for cancer immunotherapy. Finally, the Tumor Necrosis Factor
      Superfamily (TNFSF) gene DC137L was used to generate chTNT-3 antibody (targeted)
      and soluble Fc (untargeted) fusion proteins. When used alone, both forms of
      costimulatory fusion proteins were found to produce in a s dose-dependent manner,
      complete regression of murine solid tumors. Evidence is presented to show that
      Treg cells play an important role in suppressing antitumor immunity since the
      deletion of these cells, when used in combination with LEC or costimulatory
      fusion proteins, produced profound and effective treatment with sustained memory.
      It is hoped that these data will further the preclinical development of soluble
      Fc and antibody based fusion proteins fro the immunotherapy of cancer.

PMID- 18071952
TI  - The T-body approach: redirecting T cells with antibody specificity.
AB  - "T-bodies" are genetically engineered T cells armed with chimeric receptors whose
      extracellular recognition unit is comprised of an antibody-derived recognition
      domain and whose intracellular region is derived from lymphocyte stimulating
      moiety(ies). The structure of the prototypic chimeric receptor, also known as a
      chimeric immune receptor, is modular, designed to accomodate various functional
      domains and thereby to enable choice of specificity and controlled activation of
      T cells. The preferred antibody-derived recognition unit is a single chain
      variable fragment (scFv) that combines the specificity and binding residues of
      both the heavy and light chain variable regions of a monoclonal antibody. The
      most common lymphocyte activation moieties include a T-cell costimulatory (e.g.
      CD28) domain in tandem with a T-cell triggering (e.g. CD3zeta) moiety. By arming
      effector lymphocytes (such as T cells and natural killer cells) with such
      chimeric receptors, the engineered cell is redirected with a predefined
      specificity to any desired target antigen, in a non-HLA restricted manner.
      Chimeric receptor (CR) constructs are introduced ex vivo into T cells from
      peripheral lymphocytes of a given patient using retroviral vectors. Following
      infusion of the resulting T-bodies back into the patient, they traffic, reach
      their target site, and upon interaction with their target cell or tissue, they
      undergo activation and perform their predefined effector function. Therapeutic
      targets for the T-body approach include cancer and HIV-infected cells, or
      autoimmune effector cells. To date, the most investigated area is cancer therapy.
      Here, the T-bodies are advantageous because their tumor recognition is not HLA
      specific and, therefore, the same constructs can be used for a wide spectrum of
      patients and cancers.

PMID- 18071953
TI  - Intracellular antibodies (intrabodies) and their therapeutic potential.
AB  - Combining exquisite specificity and high antigen-binding affinity, intrabodies
      have been used as a biotechnological tool to interrupt, modulate, or define the
      functions of a wide range of target antigens at the posttranslational level. An
      intrabody is an antibody that has been designed to be expressed intracellularly
      and can be directed to a specific target antigen present in various subcellular
      locations including the cytosol, nucleus, endoplasmic reticulum (ER),
      mitochondria, peroxisomes, plasma membrane and trans-Golgi network (TGN) through
      in frame fusion with intracellular trafficking/localization peptide sequences.
      Although intrabodies can be expressed in different forms, the most commonly used
      format is a singlechain antibody (scFv Ab) created by joining the antigen-binding
      variable domains of heavy and light chain with an interchain linker (ICL), most
      often the 15 amino acid linker (GGGGS)(3) between the variable heavy (VH) and
      variable light (VL) chains. Intrabodies have been used in research of cancer,
      HIV, autoimmune disease, neurodegenerative disease, and transplantation. Clinical
      application of intrabodies has mainly been hindered by the availability of robust
      gene delivery system(s) including target cell directed gene delivery. This review
      will discuss several methods of intrabody selection, different strategies of
      cellular targeting, and recent successful examples of intrabody applications.
      Taking advantage of the high specificity and affinity of an antibody for its
      antigen, and of the virtually unlimited diversity of antigen-binding variable
      domains available for molecular targeting, intrabody techniques are emerging as
      promising tools to generate phenotypic knockouts, to manipulate biological
      processes, and to obtain a more thorough understanding of functional genomics.

PMID- 18071954
TI  - Benzodioxole derivative as coinitiator for dental resin.
AB  - OBJECTIVE: The aim of this work was to examine whether it was possible to
      substitute benzodioxole derivatives for amine as coinitiators for dental
      application. MATERIAL AND METHODS: A mixture of urethane dimethacrylate
      (UDMA)/triethylene glycol dimethacrylate (TEGDMA) (70/30 wt%), camphorquinone
      (CQ) and coinitiators was photocured. Real time Fourier Transform Infrared
      Spectroscopy with a horizontal sample holder was used to monitor the extent of
      polymerization. Dynamic mechanical analysis was performed over a temperature
      range from -50 degrees C to 200(o)C, with a ramping rate of 5(o)C per minute,
      using extension mode. RESULTS: Benzodioxole derivatives as coinitiator improved
      the rate of polymerization and final double bond conversion of the dental resin.
      The cured samples showed similar properties, e.g. modulus, glass transition
      temperature, water sorption and solubility. CONCLUSION: The results indicate that
      two benzodioxole derivatives, piperonyl alcohol (PAL) and benzodioxole (BDO), are
      viable alternatives to conventional amines as coinitiator. The biocompatibility
      of benzodioxole derivatives makes them more promising than amine in dental resin
      formulations.

PMID- 18071955
TI  - A two-year follow-up study of temporomandibular disorders in a female Sami
      population: validation of cases and controls as predicted by questionnaire.
AB  - OBJECTIVE: The first aim of this study was to validate persistent, severe
      symptoms of temporomandibular disorders (TMD) among Sami females, as predicted by
      questionnaire. The second aim was to establish diagnoses according to the
      Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis 1
      among predicted cases and controls. The third aim was to compare subjects with
      severe TMD to controls in regard to dental occlusion, general health, and
      parafunctions. MATERIAL AND METHODS: The subjects, Sami females living in the
      Arctic region of northern Sweden, all with long-standing (>or=1 year), intense
      (>or=5 on NS), and frequent (>or=once a week) symptoms of pain and dysfunction in
      the jaw-face region, were invited for clinical examination; 22 (63%) agreed to
      participate. Forty-six subjects with no symptoms in the jaw-face region were
      matched to these cases in accordance with five age groups. The examiner was blind
      to subject affiliation. RESULTS: The positive predictive value of presenting with
      signs and symptoms of TMD at follow-up was 0.82; the negative value was 0.87.
      Cases reported impaired general health and awareness of parafunctions
      significantly more frequently than did controls. Registered dental occlusion
      factors did not distinguish cases from controls. CONCLUSIONS: Long-standing,
      intense, and frequent TMD symptoms remained essentially unchanged over the 2-year
      follow-up of females in a Sami population. Presence of severe TMD was related to
      impaired general health and awareness of oral parafunctions.

PMID- 18071956
TI  - Effect of methotrexate on alveolar bone loss in experimental periodontitis in
      Wistar rats.
AB  - OBJECTIVE: Interleukin-1 (IL-1) and tumor necrosis factor (TNF) are pro
      inflammatory cytokines directly related with tissue destruction in the
      pathogenesis of periodontitis. Inhibitory effects on IL-1 and TNF production have
      been attributed to the folate analog methotrexate. The purpose of this study was
      to evaluate the effect of methotrexate on the pathogenesis of alveolar bone loss
      in experimental periodontitis in rats. METHODS: Ligature-induced experimental
      periodontitis was created in 44 Wistar rats. The animals were randomly divided
      into four groups and treated with methotrexate (0.1, 0.5, and 1.0 mg x kg(-1)) or
      saline. Morphometrical registration of alveolar bone loss was carried out after
      28 days of ligature placement to determine the effect of methotrexate on the
      progression of experimental periodontitis. RESULTS: Intra-group comparisons
      showed significantly higher alveolar bone loss mean values in maxillary sides
      with ligature (paired sample t-test; p<0.05). Mean alveolar bone loss was not
      different between groups and was independent of the dosage (range 0.63-0.67 mm,
      one-way ANOVA; p>0.05). CONCLUSION: Although methotrexate has important cytokine
      inhibitory properties, its possible use in modulating the host immune
      inflammatory response in periodontal disease was not confirmed.

PMID- 18071957
TI  - Effect of soft drinks on proximal plaque pH at normal and low salivary secretion
      rates.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of different types
      of drinks on plaque pH during normal and drug-induced low salivary secretion
      rates. MATERIAL AND METHODS: Three drinks were tested in 10 healthy adult
      subjects: 1) Coca-Cola regular, 2) Coca-Cola light, and 3) fresh orange juice. pH
      was measured in the maxillary incisor and premolar region with the microtouch
      method. The area under the pH curve (AUC) was calculated. RESULTS: During normal
      salivary condition, mouth-rinsing with Coca-Cola regular resulted in a slightly
      more pronounced drop in pH during the first few minutes than it did with orange
      juice. After this initial phase, both products showed similar and relatively slow
      pH recovery. Coca-Cola light also resulted in low pH values during the very first
      minutes, but thereafter in a rapid recovery back to baseline. During dry mouth
      conditions, the regular Cola drink showed a large initial drop in pH, and
      slightly more pronounced than for orange juice. After the initial phase, both
      products had a similar and slow recovery back to baseline. At most time-points,
      AUC was significantly greater in dry conditions compared to normal conditions for
      Coca-Cola regular and orange juice, but not for Coca-Cola light. Coca-Cola light
      generally showed a significantly smaller AUC than Coca-Cola regular and orange
      juice. CONCLUSIONS: The main conclusion from this study is that a low salivary
      secretion rate may accentuate the fall in pH in dental plaque after gentle mouth
      rinsing with soft drinks.

PMID- 18071958
TI  - Effect of olive oil and an olive-oil-containing fluoridated mouthrinse on enamel
      and dentin erosion in vitro.
AB  - OBJECTIVE: The study aimed to analyse the impact of olive oil and an olive-oil
      containing fluoridated mouthrinse on enamel and dentin erosion. MATERIAL AND
      METHODS: Bovine enamel and dentin specimens were submitted to 10 alternating
      demineralization and remineralization cycles each consisting of 5 min
      pretreatment with the test solutions, i.e. distilled water as negative control,
      100% olive oil, 2% olive oil emulsion, 2% olive-oil-containing mouthrinse
      (Xerostom), acidic 13.2 mmol x l(-1) (250 ppm) fluoride solution as positive
      control, storage in artificial saliva (30 min), demineralization in citric acid
      (3 min, pH 2.3) and again storage in artificial saliva (60 min). Each group
      contained 10 enamel and dentin samples. Enamel and dentin loss was analyzed by
      profilometry after 10 cycles. RESULTS: Treatment with 100% olive oil was not
      effective in reducing enamel and dentin loss. Application of 2% olive oil or the
      olive-oil-containing mouthrinse also showed protection against erosion, but to a
      lesser degree compared to the positive control. CONCLUSION: Olive oil offered
      protection against enamel and dentin erosion when applied as 2% emulsion or 2%
      olive-oil-containing mouthrinse, but is not effective when applied as pure oil
      (100%). However, 2% olive oil emulsion is less effective in reducing erosion
      compared to the acidic 13.2 mol x l(-1) fluoride solution.

PMID- 18071959
TI  - Digital images as an alternative to orthodontic casts in assessing malocclusion
      and orthodontic treatment need.
AB  - OBJECTIVE: To investigate the potential use of two-dimensional digital images as
      an alternative to orthodontic casts in the assessment of malocclusion and
      orthodontic treatment need. MATERIAL AND METHODS: Assessment of malocclusion
      (Angle's classification of molars, overjet, and overbite) and orthodontic
      treatment need (Index of Orthodontic Treatment Need (IOTN): Dental Health
      Component (DHC) and Aesthetic Component (AC)) was conducted on 313 study casts
      and their images by two trained and calibrated examiners. Agreement of
      orthodontic treatment need and Angle's molar classification was assessed
      employing Kappa statistics (kappa). Agreement of overjet and overbite (measured
      in mm) was assessed in comparison and correlation analyses. Inter- and intra
      examiner reliability of assessment was investigated. RESULTS: There was
      substantial agreement of the molar relationship classifications (kappa >0.70),
      orthodontic treatment need as assessed by IOTN-DHC (kappa =0.79) and IOTN-AC
      (kappa =0.56) between measurements obtained from orthodontic casts and their
      images. There was also substantial agreement of measurements of overjet and
      overbite as obtained from orthodontic casts and their images. The standardized
      directional differences of overjet and overbite were <or=0.2. The intra-class
      correlation coefficients of assessments of overjet and overbite obtained from
      orthodontic casts and their images were >0.90. Inter- and intra-examiner
      reliability for the assessment of malocclusion and orthodontic treatment need was
      acceptable. CONCLUSION: Two-dimensional digital images can be used as an
      alternative to casts in assessment of malocclusion and orthodontic treatment
      need.

PMID- 18071961
TI  - Sexual coercion and sexual desire: ambivalent meanings of heterosexual anal sex
      in Soweto, South Africa.
AB  - Anal sex within heterosexual relationships is usually underreported or not
      reported at all, yet is increasingly recognised as a potential mode of HIV
      transmission. Understanding the circumstances of anal sex is critical for trials
      that seek to assess the efficacy of microbicides. This article draws on
      qualitative data collected during a feasibility study for a clinical trial of
      microbicides in Soweto, South Africa. Focus groups of women enrolled in the
      feasibility study discussed the circumstances under which they and other women in
      the community had anal sex. Their narratives drew attention to the ambivalent
      meanings of anal sex; often regarded as a form of sexual coercion but also
      frequently as sexual pleasure. The article explores the reasons for these
      apparent contradictions.

PMID- 18071962
TI  - Psychological distress symptoms of individuals seeking HIV-related psychosocial
      support in western Kenya.
AB  - While researchers in many western countries have documented the nature of
      psychological distress that is commonly present among individuals living with
      HIV, there has been virtually no research on the same topic among other high
      prevalence areas of the world, particularly in countries like Kenya. This study
      sought to document the nature of psychological distress among 397 individuals
      living with HIV in western Kenya and who were participating in psychosocial
      support groups in conjunction with their enrollment in HIV-related treatment.
      Psychological distress was assessed using the Brief Symptom Inventory (BSI), a 53
      item self-report psychological inventory that asks individuals to recall symptoms
      experienced in the prior seven days. The levels of psychological distress in this
      sample were moderate with a substantial proportion of participants meeting the
      criteria that suggested a need for further psychiatric evaluation. Findings
      support the need for further assessments of the range and nature of psychological
      distress among the diverse communities of countries like Kenya and the need for
      greater attention to the inclusion of mental health services in the rapidly
      developing treatment and prevention programs in this region of the world.

PMID- 18071963
TI  - Factors associated with prevalence of mental disorder in people living with
      HIV/AIDS in South Africa.
AB  - The study examines the association between the presence of mental disorder and a
      range of independent variables. A sample of 900 HIV-positive individuals was
      administered the Composite International Diagnostic Interview to determine the
      presence of selected mental disorders. A structured interview assessed support
      received and factors that may contribute to mental disorder. Overall prevalence
      of mental disorder was 43.7%--though higher in Stage 3 (49.7%) and in Stage 4
      (68%) of the disease. Eighteen percent of respondents were receiving
      antiretroviral treatment. Having had pre- and post-test counselling was not
      related to mental disorder; nor were the number of sessions, the professional
      status of the counsellor and perceived helpfulness of counselling. Being in an
      HIV support group was related to presence of a mental disorder, although the
      frequency of attendance was not. Although most of those who disclosed their HIV
      status found the experience helpful there was a significant positive association
      between presence of a mental disorder and having disclosed HIV-positive status.
      Although being a member of an association for people with HIV/AIDS and being
      religious was perceived as helpful, neither was statistically associated with the
      presence of mental disorder. Discrimination by community and family and isolation
      were related to mental disorder. Death of a significant other due to AIDS was
      related to mental disorder. The findings suggest a strong need for provision of
      psychiatric care as part of AIDS care as well as strengthening of support
      services.

PMID- 18071964
TI  - Reasons for ART non-adherence in the Deep South: adherence needs of a sample of
      HIV-positive patients in Mississippi.
AB  - HIV prevalence in the American Deep South has reached crisis proportions and
      greater numbers of patients are enrolling in clinical care and beginning
      antiretroviral therapy (ART). In order to gain maximum benefit from ART, patients
      must sustain high levels of adherence to demanding regimens over extended periods
      of time. Many patients are unable to maintain high rates of adherence and may
      need assistance to do so, which may be based upon an understanding of barriers to
      adherence for a given population. The current study sought to gain understanding
      of barriers to adherence for a mixed urban/rural HIV-positive patient population
      in Mississippi and to determine whether barriers to adherence may be specific to
      gender, employment, depressive symptoms or educational attainment status. Seventy
      two patients who missed a dose of ART medication over the last three days
      endorsed the top five reasons for missing a dose as: (1) not having the
      medication with them, (2) sleeping through the dose time, (3) running out of the
      medication, (4) being busy with other things and (5) other. Reported barriers
      were fairly consistent across different groups, although women and those
      classified as having moderate to severe depressive symptoms reported different
      patterns of adherence barriers. Results suggest that adherence interventions
      implemented in the Deep South must take into account specific barriers faced by
      individuals within this region, where stigma, gender disparities and limited
      resources are prevalent.

PMID- 18071965
TI  - The impact of mental health, sexual desire and sexual importance on the sexual
      behaviour of women with HIV.
AB  - HIV infection is increasing among women in the US, particularly among racial
      minority groups. The hypothesized theoretical model considered the extent to
      which indicators of depression, sexual desire and sexual importance would predict
      whether sexual behaviour would occur for a sample of 96 women with HIV. The
      results of this study supported previous findings that depression significantly
      decreases the chances that sexual behaviour will occur, while sexual desire and
      sexual importance moderately increased the chance occurrence of this variable.
      The results of this study suggested that the mental health of women with HIV
      significantly affects whether they engage in sexual behaviour. HIV-prevention and
      intervention models need to be more inclusive of those factors that are most
      salient in the sexual relationships of women. Moreover, additional research is
      needed to examine the importance of maintaining sexual behaviour for women with
      HIV.

PMID- 18071966
TI  - The effect of perceived and actual social support on the mental health of HIV
      positive persons.
AB  - The purpose of this paper is to compare the ways in which perceived and actual
      social support affect the mental health of gay men, straight or bisexual men, and
      women living with HIV/AIDS. Participants included 125 women and 232 men with an
      HIV-positive or AIDS diagnosis involved in three larger investigations of HIV,
      disclosure and mental health. Results suggest each sub-group experienced
      perceived social support as significantly predictive of better mental health
      while the effect of actual social support was minimal.

PMID- 18071967
TI  - Associations between stigmatization toward HIV-related vulnerable groups and
      similar attitudes toward people living with HIV/AIDS: branches of the same tree?
AB  - This study tested the hypothesis that stigmatization toward people living with
      HIV/AIDS (PLWHA) was associated with stigmatization toward different vulnerable
      groups, including men who have sex with men (MSM), injecting drug users (IDUs),
      female sex workers (FSW) and their clients (CFSW). A number of scales and
      indicators were constructed for the purpose: the four Overall Stigmatization
      Scale for a Vulnerable Group (OSSVG) and the five Dimensional Stigmatization
      Scale (DSS) each measuring different dimensions of stigmatization toward the four
      vulnerable groups, together with four indicators measuring stigmatization toward
      PLWHA. A random sample of 2,008 Hong Kong Chinese adults aged 18-50 years in the
      general population were interviewed by telephone. Of these respondents, 22.8-
      76.8% perceived that FSW, CFSW, MSM and IDU were pathological and 42-82.2%
      perceived them as immoral; 74.7% believed that PLWHA are promiscuous.
      Furthermore, the four OSSVG and the five DSS scales were inter-correlated with
      one another (Spearman coefficient = 0.11-0.67) and most of them were
      significantly associated with the four PLWHA stigmatization indicators (Odds
      Ratio = 1.25-4.27). Other factors were associated with the OSSVG and DSS scores
      (e.g. age, marital status, religion affiliation, education level, income and
      perceived severity of the HIV problem in Hong Kong). Campaigns for removing
      stigmatization toward these vulnerable groups are required in order to reduce
      stigmatization toward PLWHA. Stigmatization toward FSW and their clients might
      have been over-looked. The removal of the public's blame on these groups for
      spreading HIV may be useful. The impact of HIV prevalence of a vulnerable group
      onto the associations between stigmatization toward that particular group and
      PLWHA warrants investigation.

PMID- 18071968
TI  - The emotional aspect of AIDS stigma among health professionals in Puerto Rico.
AB  - People who live with HIV/AIDS (PLWHA) in Puerto Rico have been a vulnerable group
      for stigmatization. Emotions have been a widely ignored issue in stigma-related
      research. Emotions influence the way people establish their relationship with
      their environment, relate to each other and assign social meanings to who and
      what surrounds them. Therefore, emotions have a vital role in the stigmatization
      of PLWHA. The main objective of this study was to explore the role of emotions in
      the process of stigmatization of PLWHA by health professionals and health
      profession students. We implemented an exploratory and mixed method design
      integrating semi-structured interviews and self-administered questionnaires. The
      sample was composed of 501 health professionals and health profession students.
      Qualitative results evidenced the role of negative emotions, such as fear, pity,
      disgust and embarrassment, in the stigmatization of PLWHA. Participants also
      described emotions as phenomena that should be suppressed in order to provide
      effective services. Quantitative results evidenced the manifestation of negative
      emotions for most of the situations presented to them related to HIV/AIDS.
      Emotions manifested in health scenarios can hinder the productive provision of
      health-related services and therefore should be addressed as part of stigma
      reduction interventions.

PMID- 18071969
TI  - HIV-positive women in northeast Brazil: tubal sterilization, medical
      recommendation and reproductive rights.
AB  - Tubal sterilization is the most common contraceptive method used by Brazilian HIV
      positive women. This cross sectional study describes the main reasons why HIV
      positive women decide to be sterilized and identifies factors associated with
      choosing sterilization in HIV-positive women in Ceara, northeast Brazil. Data
      from 229 non-sterilized women, 80 women sterilized before HIV diagnosis and 48
      women sterilized after diagnosis were analysed. Of the women sterilized after HIV
      diagnosis, 96% had the procedure done in the postpartum, during a caesarean
      section. No desire for more children was the most common appointed reason to be
      sterilized (39.6%), followed by medical recommendation because of HIV (31.3%).
      Seventy-nine women (28.5%) had a child after HIV diagnosis. Of those, 46 (58.2%)
      were sterilized in the postpartum. Factors associated with sterilization for HIV
      positive women were: having a child after diagnosis (AOR: 120.9; 95%CI: 27.8
      525.4) and having at least three children (AOR: 2.8; 95%CI: 1.1-7.1). It is
      recommended that non-coercive counselling should be provided so that HIV-positive
      women can make informed decisions on their reproductive options.

PMID- 18071970
TI  - Unhealthy behaviours for self-management of HIV-related peripheral neuropathy.
AB  - The prevalence of peripheral neuropathy is frequent in HIV disease and is often
      associated with antiretroviral therapy. Unhealthy behaviours, particularly
      substance-use behaviours, are utilized by many HIV-positive individuals to manage
      neuropathic symptoms. As part of a larger study on self-care for symptoms in HIV
      disease, this study analyzed the prevalence and characteristics of unhealthy
      behaviours to self-manage peripheral neuropathy in HIV disease. Sociodemographic
      and disease-related correlates and unhealthy behaviours were examined in a
      convenience sample of 1,217 respondents who were recruited from data collection
      sites in several US cities, Puerto Rico, Colombia, and Taiwan. Results of the
      study indicated that respondents with peripheral neuropathy (n=450) identified a
      variety of unhealthy self-care behaviours including injection drug use, oral drug
      use, smoking cigarettes and alcohol ingestion. Specific unhealthy behaviours that
      participants reported to alleviate peripheral neuropathy included use of
      marijuana (n=67), smoking cigarettes (n=139), drinking alcohol (n=81) and street
      drugs (n=30). A subset of those individuals (n=160), who identified high levels
      of neuropathy (greater than five on a scale of 1-10), indicated significantly
      higher use of amphetamines and injection drug use in addition to alcohol use and
      cigarette smoking. For participants from Norway, substance use (using alcohol:
      56%) was one of the most frequent self-management strategies. Implications for
      clinical practice include assessment and education of persons with HIV for self
      care management of the complex symptom of peripheral neuropathy.

PMID- 18071971
TI  - Sex work in the Caribbean Basin: patterns of substance use and HIV risk among
      migrant sex workers in the US Virgin Islands.
AB  - Drug use, commercial sex work, and migration each play a role in the spread of
      HIV in the Caribbean, yet the intersection of these factors in the region is not
      well understood. This paper explores the connections between substance use and
      HIV risk among migrant female sex workers in the US Virgin Islands. Participants
      were located through targeted sampling techniques in Christiansted and
      Frederiksted, St. Croix, and Charlotte Amalie, St. Thomas where 101 women were
      interviewed regarding their drug use, sexual behaviours, migration patterns and
      health status. In the month prior to interview, 25.7% reported no substance use,
      57.4% reported alcohol use only and 16.8% indicated use of an illicit drug. Drug
      using sex workers reported a significantly greater number of past-month sexual
      partners than alcohol-only and non-drug users. In logistic regression analyses,
      illicit drug users were significantly more likely to report unprotected sexual
      activity, client violence and sexually transmitted infections as well. In
      addition, illicit drug users engaged in sex work in a significantly greater
      number of countries and were more likely to work in locations outside the US
      Virgin Islands. The intersection of multiple risk factors for HIV identified
      among drug-involved sex workers in the region, including unprotected sexual
      activity with multiple partners, violent victimization and migration between high
      and low HIV-prevalence areas, suggests that illicit drug use may play an
      important role in driving the growing heterosexual HIV epidemic in the Caribbean.

PMID- 18071972
TI  - Association of misconceptions about HIV transmission and discriminatory attitudes
      in rural China.
AB  - This study examined HIV-related knowledge and attitudes among 524 randomly
      selected adult residents from 12 rural Chinese communities where HIV infection
      among plasma donors has been reported. Most participants were familiar with the
      main routes of HIV transmission but had substantial misconceptions about risk of
      HIV transmission through casual social contacts. Higher score of misconception
      and being older and married independently predicted stronger discriminatory
      attitude. Intervention programs with focus on eliminating misconceptions about
      HIV transmission may reduce stigma.

PMID- 18071973
TI  - Vulnerable but feeling safe: HIV risk among male rural-to-urban migrant workers
      in Chengdu, China.
AB  - HIV prevalence is increasing in China. The proportion of infection attributable
      to heterosexual sex in China is also on the rise. The scale of internal migration
      for work is likely to be one of the factors contributing to these changing
      patterns, but little is known about HIV-related knowledge, perceptions and risk
      behaviours of China's migrant workers. This study aimed to investigate HIV
      related knowledge, attitudes and risk behaviours of male rural-to-urban migrant
      workers in Chengdu and to identify factors associated with risk behaviours. In
      2005, a cross-sectional questionnaire survey was completed by 163 male
      construction- and factory-based migrant workers aged 18-35 years. With a mean age
      of 26 years, just 30% had completed senior middle school and 47% were currently
      married. Respondents were highly mobile, worked long hours and were relatively
      poorly paid. As migrants, their access to urban services and benefits was
      restricted, making it difficult for family members to join them. Knowledge of HIV
      transmission was generally poor and discriminatory attitudes towards people with
      HIV were commonplace. Seventy-five percent were sexually experienced, among whom
      88% had had sexual relations in the last 12 months. Of these, 30% had had two or
      more partners and 20% had paid for sex. Just 36% had used a condom during the
      most recent sexual encounter with a sex worker. Around 70% thought it was
      'impossible' for them to become infected, yet a significant sub-group were
      engaging in sexual behaviours that place them at risk of infection with HIV and
      sexually transmitted infections (STIs). Logistic Regression found a significant
      association between having multiple sexual partners and both education level and
      marital status. Education was also found to be significantly associated with
      purchasing sex. Targeted HIV-prevention programs for male migrant workers in
      Chengdu, especially for those who are single and less educated, are urgently
      needed.

PMID- 18071974
TI  - Social determinants for HIV prevalence among South African educators.
AB  - HIV prevalence among women in South Africa continues to be high despite the
      availability of a comprehensive plan for the control of HIV/AIDS and a plethora
      of prevention programmes. Any explanation for the ongoing high HIV prevalence
      continues to be elusive. The objective of this study was to understand the
      relationship between HIV, gender, race and socioeconomic status among South
      African public sector educators in order to inform prevention programmes. A cross
      sectional survey involving a probability sample of 1,766 schools out of 26,713 in
      the Department of Education Register of School Needs was selected. A sample of
      24,200 respondents out of 356,749 public sector educators participated in the
      study. Nurses registered with the South African Nursing Council were recruited,
      trained to conduct interviews and to collect specimens for HIV testing. The study
      found an association between HIV, gender, race and socioeconomic status among
      educators. African educators showed a higher HIV prevalence than other race
      groups. Among females, the highest HIV prevalence was among educators aged 25-35
      years and in males aged 36-49 years. Further, educators with a high income and
      educational qualifications had a lower HIV prevalence compared to educators with
      low income and low educational qualifications, regardless of sex. Migration and
      marital factors were also found to play a role in HIV infection. The results
      suggest that HIV prevention needs to take into account critical issues around
      empowerment of vulnerable groups such as women and certain race groups to be able
      to implement safe sexual practices and therefore reduce HIV infections.

PMID- 18071975
TI  - Improving HIV management in sub-Saharan Africa: how much palliative care is
      needed?
AB  - The WHO advocates palliative care as an essential component of HIV care from the
      point of diagnosis (when the burden of pain and symptoms may be first
      experienced) to the end of life and into bereavement (World Health Organisation,
      2006). However, in the field of African HIV care where mortality is high,
      palliative care has been shown to be largely lacking. This study aimed to measure
      the prevalence of multidimensional palliative care needs of patients with HIV
      disease in Muheza, Tanzania. A prospective census measured presenting problems
      for all patients during a one-month period: professional contact; physical
      symptoms; psychosocial problems; prescribing; and care planning. During the four
      week period of the study, 731 patients attended for HIV care. The total number of
      professional contacts was 1,512, with 736 nurse, 733 doctor and 43 social worker
      contacts. Patients were identified as being appropriate for palliative care if
      they needed pain relief other than simple paracetamol or if they or their family
      had complex pain or physical, psychosocial or spiritual needs. The mean patient
      age was 35.4 years (SD=13.7) and 82 patients were under the age of 16. The
      majority were female (70.9%). Morphine was being prescribed to 21 patients (2.8%)
      and ART was being prescribed to 434 (59.4%). The mean CD4 count was 178.3 cells
      mm(3) (Median=131.1; SD=179.9). Palliative care intervention was indicated for
      378 (51.7%) patients. Among those 434 patients using ART, 230 (52.9%) were
      indicated as having palliative care needs. Palliative care continues to be an
      important part of HIV programmes even in the presence of ARV treatment.

PMID- 18071976
TI  - Is participation in HIV vaccine trials a health promoting behaviour?
AB  - Health behaviours are individual acts by which people aim to preserve or enhance
      their health. Theories commonly used to understand health behaviour include the
      Health Belief Model, the Theories of Reasoned Action and Planned Behaviour, the
      Transtheoretical Model of Change, Social Cognitive Theory and Problem-Behaviour
      Theory. Targets for health-promotion interventions include exercise, smoking
      cessation and condom use. Some behaviours that may contribute to changes in
      population health, however, are not health behaviours as traditionally
      understood. For example, participating in an HIV vaccine trial may have the
      potential to contribute long-term to lowering HIV incidence. To what extent,
      though, can or should we apply models of health behaviour to HIV vaccine trial
      participation? This article grapples with the theoretical challenges facing
      social scientists who conduct research related to HIV vaccine trial
      participation. We initially consider decision making regarding trial
      participation from both the participant and investigator perspectives, before
      considering how these alternate decision-making narratives might impact on the
      conduct of HIV vaccine trials. We conclude by arguing that social scientists need
      to move beyond a narrow focus on health promotion theory and to engage in the
      interrelated scientific activities of theory testing and theory building.

PMID- 18071977
TI  - Impact of antiretroviral therapy on vocational rehabilitation.
AB  - This study evaluates the impact of a free antiretroviral therapy (ART) programme
      on the employment status of people living with HIV/AIDS. Patients on ART were
      interviewed regarding the employment status before and after ten months of
      enrollment into therapy. We included patients who were started on the free ART
      program of Kerala state at the Medical College, Thrissur. We documented the
      demographic details, indication for starting ART, disease status, WHO staging and
      CD4 count (whenever available) and the job status at the time of enrollment into
      the study. We collected data about the patient's job status at the end of ten
      months of ART. We excluded patients below 20 years of age, those who died during
      the study period and those lost for follow-up before the end of ten months from
      the analysis. We looked at factors associated with having employment at the end
      of ten months of ART using logistic regression. At the end of ten months of
      therapy the employment status improved significantly (p<0.01) to 74% (77
      patients). We found that 96.4% of those previously employed are at present
      employed, while 65.8% of those previously unemployed are employed at present. A
      history of previous employment (p=0.014) was associated with acquisition of
      employment; sex, duration on ART, stage of disease or age does not significantly
      influence the present employment status. This study suggests that the provision
      of free ART by the state can significantly improve the employment status of
      PLWHA.

PMID- 18071978
TI  - Sexual assault in childhood: risk HIV and AIDS behaviours in adulthood.
AB  - This study examined the hypothesis that sexual assault in childhood is a risk
      factor in HIV and AIDS prevention and control in adulthood. It comprised 40
      participants who were survivors of child sexual abuse and 40 participants who
      were not sexually abused. The sample had 20 sexually abused men, 20 non sexually
      abused men, 20 sexually abused women and 20 non sexually abused women. The group
      that had men and women who had a history of sexual assault reported higher HIV
      and AIDS risk behaviours than the non-abused comparison group. The survivors of
      sexual assault also had higher levels of post-traumatic stress disorder,
      depression, suicide ideation and external locus of control. They reported low
      self-esteem. This unhealthy psychological functioning was found to be a risk
      factor in HIV and AIDS prevention and control. Implications for future research
      are discussed.

PMID- 18071980
TI  - Empty sella syndrome associated with a hyperfunctioning microadenoma invading the
      clivus.
AB  - The empty sella syndrome is usually associated with normal pituitary function. If
      dysfunction is present, this is commonly hypofunction. Hyperfunctioning
      microadenomas have been described in the presence of the empty sella syndrome. We
      present the first reported cases of a microadenoma invading the clivus associated
      with an empty sella.

PMID- 18071981
TI  - The Children's Cancer and Leukaemia Group guidelines for the diagnosis and
      management of dysembryoplastic neuroepithelial tumours.
AB  - Dysembryoplastic neuroepithelial tumours (DNETs) were incorporated into the new
      World Health Organization classification of brain tumours as part of the group of
      glioneuronal tumours in 1993. Large series of patients with DNETs and pharmaco
      resistant epilepsy have been reported. DNETs are most often located in the
      temporal lobe, occurring in both mesial and lateral temporal locations. DNETs
      have also been reported in the insular cortex, brain stem, cerebellum, occipital
      lobe and striatum. Approximately 40% of DNETs are cystic, and solitary nodular,
      multinodular or diffuse forms have been recognized. Approximately 30% of DNETs
      are associated with subtle cortical dysplastic changes in the adjacent cortex.
      DNET nodules usually look like oligodendroglioma, whilst between the nodules it
      may be possible to recognize vertical columns of neurons surrounded by
      oligodendrocyte-like cells. Cytologically, oligodendroglial-like cells of DNETs
      are distinguished from oligodendroglioma by larger nuclei with frequent nuclear
      indentations and multiple, small nucleoli, whilst oligodendrogliomas consistently
      show nuclear roundness with one or two occasional nucleoli. Very rare cases of
      malignant transformation have been reported. DNETs are hypodense on CT and
      demonstrate decreased signal on the T1-weighted images and a hyper-intense signal
      on T2-weighted MRI. DNETs associated with pharmaco-resistant epilepsy should be
      removed early to achieve seizure freedom and prevent tumour progression. The
      surgical approach should be that of an extended lesionectomy, i.e. excision of
      the lesion and the abnormal dysplastic cortex around it. Use of MRI-based image
      guidance (neuronavigation) as a surgical tool to identify this area of abnormal
      cortex is very helpful to ensure that the extended lesionectomy includes any
      visibly dysplastic cortex. It is not advocated to use a stereotactic biopsy only,
      as this may generate an unrepresentative tissue sample consisting of an
      oligodendroglial component only and may lead to an incorrect diagnosis.

PMID- 18071982
TI  - Advanced MRI in the management of adult gliomas.
AB  - Gliomas are a heterogeneous group that account for approximately 86% of primary
      brain neoplasms, and include astrocytic and oligodendroglial tumours, as well as
      a variety of less common histopathological subtypes. Magnetic resonance imaging
      has become the accepted mode of imaging for the clinical management of these
      tumours. MRI features bear close resemblance to the histopathology grading and
      prognosis of these tumours. Currently, conventional MRI is used to aid diagnosis,
      plan neurosurgical approaches, and monitor response to therapy and disease
      progression. More recent developments in the field of MRI include MR
      spectroscopy, perfusion MRI, diffusion-weighted imaging, intraoperative MRI and
      functional MRI. These newer techniques have been adopted with varying success in
      the management of adult gliomas. This review focuses on the application of
      advanced MR imaging in the clinical management of adult gliomas.

PMID- 18071983
TI  - The role of advanced MR imaging in understanding brain tumour pathology.
AB  - Although MRI is the imaging modality of choice for brain tumours, the standard
      clinical sequences cannot tell us about certain features of brain tumours.
      Improvements in imaging technology now allow advanced sequences, once used
      exclusively for research, to be used clinically. Assessment of brain tumours with
      diffusion weighted MR (a marker of cellularity), diffusion tensor MR (shows
      integrity of surrounding white matter tracts), perfusion MR (marker of tumour
      vascularity and angiogenesis), MR spectroscopy (showing tumour metabolism) and
      functional MR (to identify eloquent cortex) provide information that is
      complementary to the structural information. These techniques can be used to
      improve identification of the tumour margin, tumour grading, reducing surgical
      risk and assessing the response to therapy. It is important for the neurosurgeon
      to understand what information can be obtained from these sequences, and that
      they ensure they are used to further develop the assessment and management of
      brain tumours.

PMID- 18071984
TI  - Proteomic analysis of gliomas.
AB  - Primary malignant brain tumours (anaplastic glioma and glioblastoma) display
      heterogenous histopathology and diverse genetic abnormalities. These tumours
      remain incurable with no significant improvement in median survival times in the
      last 20 years, despite significant technological advances in surgery and
      radiotherapy, and mechanistic insights into their aetiology. Recent clinical
      trials suggest molecular characterization of tumours is essential in guiding both
      therapy and predicting prognosis. Genetic insight into tumour biology and
      increasingly proteomic technology has opened new avenues for novel applied
      clinical research. Protein expression in human malignant glioma and matched
      normal brain tissues can now be reliably analysed using quantitative proteomic
      techniques, the most accessible of which is two-dimensional gel electrophoresis
      (2DGE) and matrix-assisted laser desorption ionization time of flight (MALDI-TOF)
      mass spectrometry from which differentially expressed proteins can be identified
      and characterized. The potential of using differential proteomic profiling in
      gliomas to identify prognostic markers and to gain insight into tumour biology is
      currently being investigated. The current status of proteomic technology, its
      application to gliomas and the utility of such translational studies is reviewed.

PMID- 18071985
TI  - Encouraging experience of concomitant Temozolomide with radiotherapy followed by
      adjuvant Temozolomide in newly diagnosed glioblastoma multiforme: single
      institution experience.
AB  - The purpose of this study was to report our experience with concomitant and
      adjuvant temozolomide (TMZ) with radiotherapy in patients with newly diagnosed
      glioblastoma multiforme (GBM). Forty-two newly diagnosed histopathologically
      proven patients with GBM underwent maximal safe resection followed by external
      radiotherapy to a total dose of 60 Gy in 30 fractions over 6 weeks along with
      concomitant oral TMZ (75 mg/m2) daily followed by adjuvant TMZ for 5 days every
      28 days for six cycles (150 mg/m2 for the first cycle and 200 mg/m2 for rest of
      the cycles). Patients were monitored clinicoradiologically as per standard
      practice. Patients were 13-69 years of age with a median age of 49.5 years (31
      males, 11 females). Fifty per cent of patients underwent a gross total resection
      of tumour, 43% had partial resection, and 7% an open or stereotactic biopsy only.
      53% of the patients had a post-operative Karnofsky Performance Score (KPS) of 60
      80%. All patients received concomitant radiation and TMZ with 74% of the patients
      completing six cycles of adjuvant TMZ. At a median follow-up of 12.5 months, the
      1- and 2-year survival was 67 and 29%, respectively. The median overall and
      progression-free survival was 16.4 and 14.9 months respectively. Patients with
      pretreatment KPS of >80% had significantly better overall survival as compared
      with those having KPS<or=80% (median survival 22.12 vs. 11.97 months; p=0.026).
      Treatment was generally well tolerated with 9% of patients developing grade 3
      anaemia, 2% grade 3 leucopoenia, and 7% patients grade 3 or 4 thrombocytopenia
      respectively during the treatment. At last follow-up, among the surviving
      patients, 30% had a maintained KPS greater than 90%. Concomitant radiotherapy and
      TMZ followed by adjuvant TMZ prolongs survival in patients with glioblastoma
      multiforme and is well tolerated in our patient population.

PMID- 18071986
TI  - Atypical meningiomas: WHO moved the goalposts?
AB  - The histological grading of meningiomas underwent substantial revision and
      standardization in a WHO review of 2000. Prior to this the histological
      definition of atypical and malignant meningiomas was less tightly defined. We
      conducted a retrospective analysis of all meningiomas operated on between 1993
      and 2003 in our unit (n=565), to assess whether the WHO changes had altered the
      proportion of tumours diagnosed as atypical. The percentage of tumours graded WHO
      II (atypical meningiomas) has increased significantly since these changes were
      adopted (18.3-23.1%, p=0.0408). We also examined the epidemiology of meningioma,
      finding that previous irradiation is associated with atypical meningiomas
      (p=0.038) and surgeons find that complete excision is also more difficult with
      atypical tumours (p=0.010), reporting poorer Simpson grades intraoperatively
      before the tumour grade is known. The increase in atypical lesions caused by the
      grading changes may lead to a corresponding increase in the numbers of patients
      referred for radiotherapy/radiosurgery, and we examine the evidence base for this
      strategy and whether our experience is replicated in other units.

PMID- 18071987
TI  - The surgical management of metastatic spinal disease: prospective assessment and
      long-term follow-up.
AB  - The last decade has witnessed a resurgence of interest in the surgical treatment
      of metastatic spinal disease to compliment radiotherapy. A recent randomized
      controlled trial looking directly at this issue concluded strongly in favour of a
      combination of surgical decompression and radiotherapy, and there is now growing
      enthusiasm for surgery to play a role in the management of these patients. We
      present a prospective cohort study of 62 patients who presented with metastatic
      cord or cauda equina compression, and were treated with surgical decompression
      and fixation where necessary. Patients were treated by one surgeon working in a
      single unit. They were followed-up long term and were assessed objectively, by
      clinical assessment and prospective questionnaires that included SF36, visual
      analogue pain scores and Roland Morris back pain scores. Sixty-two patients with
      a median age of 62 (22-79 years, 27 male) were included in the study. The
      commonest primary tumours were breast (26%) and lymphoma (13%). The majority of
      patients had involvement of thoracic vertebrae (58%). 56% of patients were alive
      at 1 year and 28% at 3 years, with significant improvements observed in both
      walking and continence. Similarly, significant improvements were seen in SF36
      quality of life scores as well as pain. With careful patient selection, long-term
      survival and good quality of life can be achieved. However, not every patient is
      suitable or appropriate for surgery, and the discussion focuses on where the
      surgical threshold should be set.

PMID- 18071988
TI  - Surgical management for glossopharyngeal neuralgia associated with cardiac
      syncope: two case reports.
AB  - Two patients with glossopharyngeal neuralgia associated with cardiac syncope were
      treated with temporary cardiac pacemakers for cardiac syncope and then
      microvascular decompression. The offending arteries were the posterior inferior
      cerebellar artery in one patient and the anterior inferior cerebellar artery in
      the other. The offending arteries were attached to the glossopharyngeal nerve and
      the vagal nerve at the root entry zones. After surgery, the patients were free
      from neuralgia and cardiac syncope did not occur after the pacemakers were
      extracted. Implantation of a temporary cardiac pacemaker in the perioperative
      period ensures safe microvascular decompression.

PMID- 18071989
TI  - Suppurative intracranial complications of sinusitis in adolescence. Single
      institute experience and review of literature.
AB  - The objective of this study was to investigate the outcome of neurosurgical
      treated children with suppurative intracranial complications (SIC) of sinusitis
      over the past 28 years in our hospital. We reviewed the cases notes of a series
      of 11 consecutive paediatric patients, who were subjected to surgery for
      sinusitis-induced SIC, retrospectively. Eleven children (10 males and only one
      female) were underwent neurosurgical procedure in our hospital between 1978 and
      2006. Their age at the time of diagnosis ranging from 13 to 17 years (mean 15.27
      years, SD 1.737). The commonest presenting symptoms were headaches (81.8%)
      followed by vomiting (45.5%) and swelling of the forehead (45.5%). The most often
      involved sinus was the frontal sinus (63.6%) and sinus surgery was performed in
      eight (72.72%) of 11 cases. The neurosurgical procedures carried out included
      burr hole drainage or aspiration of abscess in five cases, craniotomy and
      evacuation of empyema in seven cases and craniectomy in two cases. Four (36.4%)
      of 11 patients had more than one neurosurgical operation due to re-accumulation
      of pus and worsening of their clinical status. Most common pathogen was
      Streptococcus species (81.9%), and anaerobes were isolated in three (27.3%)
      cases. Postoperative antibiotic treatment lasted from 26 to 70 days (mean 45.45
      days, SD 15.280). Epilepsy was diagnosed in two patients, postoperatively. During
      the follow-up period, persistent focal neurological deficits were present in five
      (45.5%) of 11 patients. Interestingly, five (45.45%) cases occurred over the last
      2 years (2005-2006) and the other six over the previous 16 years (1978-2006).
      Prompt and aggressive medical and neurosurgical intervention is required, aiming
      to minimize the morbidity and mortality and also to maximize the favourable
      outcome of those children.

PMID- 18071990
TI  - A clinical audit of neurosurgical bed usage.
AB  - AIM: To investigate inefficiencies during patients' stay in neurosurgical beds.
      METHODS: A prospective audit of neurosurgical inpatients was conducted over
      approximately 2 months. We recorded the causes and duration of inappropriate
      delays, defined as actions requiring more that 24 h from initiation until
      completion. RESULTS: One-hundred-and-thirty-eight patients were studied (61
      elective and 77 emergency admissions). The audited patients were in hospital for
      a total of 1665 days. Of these, 482 days (29%) were due to delays. 92.5% of these
      wasted days involved emergency admissions. The main categories of delay were
      transfer back to referring hospital (46% of all delays), operative (26%) and
      radiological (19%). Our own hospital was responsible for the longest transfer
      delays (6.3 days/patient compared with an average of 2.8 for all hospitals).
      Operative waits arose because of problems with both the timing and capacity of
      lists. Radiological delays resulted in particular from waits for MRI scans and
      neuroradiologist-performed procedures. The effect of eliminating all these
      inappropriate delays would be equivalent to liberating 10.7 of our 37
      neurosurgical beds at any one time. CONCLUSIONS: Clinician-led analysis of
      organizational aspects of patient care has revealed serious structure, process
      and capacity problems in efficient bed usage, We have made proposals to address
      the cause of the inappropriate delays.

PMID- 18071992
TI  - Intracranial epidural abscess secondary to isolated sphenoid sinusitis.
AB  - Isolated sphenoid sinus infection, although an uncommon entity, can cause severe
      cranial complications when left untreated. A case of temporal epidural abscess
      secondary to isolated sphenoid sinusitis in a 13-year-old boy is presented. Early
      diagnosis and treatment are critical because the disease can progress rapidly.

PMID- 18071993
TI  - Neuroendoscopic palliation for large cystic craniopharyngioma in an elderly
      patient.
AB  - We describe the case of a 74-year-old man with large mixed craniopharyngioma who
      was successfully treated under the concept of neuroendoscopic palliation. He
      recovered immediately postoperatively and has done well in the 4 years following
      surgery.

PMID- 18071994
TI  - A case of intractable nausea and vomiting following posterior fossa craniotomy.
AB  - We describe a unique case of prolonged nausea and vomiting following posterior
      fossa craniotomy for removal of a meningioma. No apparent neurological or
      gastrointestinal causes were discovered except for a delayed gastric emptying
      time. The symptoms gradually resolved along with normalization of the gastric
      emptying time. Possible pathogenic mechanisms are discussed.

PMID- 18071995
TI  - Double aggressive osteoblastomas of calvarium.
AB  - A 55-year-old female presented with a painful protruding mass in right parietal
      skull for 7 months. Interestingly, another smaller bony lesion, separated from
      the symptomatic one, was disclosed in right frontal skull on imaging study. The
      larger one was completely excised, first with a picture of an aggressive
      osteoblastoma in the pathology. The smaller one in the frontal skull was excised
      subsequently, presenting the same pathological picture as the larger one. No
      other foci of osteoblastomas were detected on the whole body bone scan. To our
      knowledge, this is the first case with double independent osteoblastomas
      occurring in frontal and parietal skull. Surgical strategy for these two bony
      lesions was discussed.

PMID- 18071996
TI  - Calvarial lymphoma.
AB  - Meningioma-like dura based tumours or the radiological pictures of suspicious
      looking meningiomas may turn out to be lymphomas.

PMID- 18071999
TI  - Blurred vision and headaches in a patient with hydrocephalus is not always due to
      shunt malfunction.

PMID- 18072000
TI  - The early diagnosis of spinal tumours. A personal story spanning 50 years.

PMID- 18072001
TI  - Meta-analysis and the timing of cauda equina surgery.

PMID- 18072003
TI  - ICT-based health information services for elderly people: past experiences,
      current trends, and future strategies.
AB  - Although health information is readily available on the Internet and has changed
      the way people deal with their health in many ways, the retrieval of relevant
      information remains problematic, especially for elderly people. With a focus on
      elderly people, this paper summarizes current trends in consumer health
      informatics, discusses past and present initiatives providing health-information
      services, and proposes a future strategy for the design of sustainable services.
      A systematic literature review and a review of past German and EU projects
      concerned with health information services for elderly people are given. Many
      publications focus on health information services for specific diseases and on
      their quality and semantic accessibility, yet few deal with presenting and
      customizing health information for elderly and disabled people. Past experiences
      from Germany suggest that very often the specific needs of this target group are
      not met, and therefore accessibility remains largely hypothetical. We propose a
      strategy with five key points for the design of sustainable health-information
      services for elderly people. More research is needed to customize web-based
      health information services to the needs of the user group that needs them most
      urgently - elderly and disabled people.

PMID- 18072004
TI  - Readability and cultural sensitivity of web-based patient decision aids for
      cancer screening and treatment: a systematic review.
AB  - Decision aids (DA) can inform cancer screening. We conducted a systematic review
      of web-based, cancer DA to evaluate their appropriateness for use with low
      literacy and diverse culture groups. Eighty-one Internet DA were found searching
      five databases (Pubmed-Medline; Web of Science/SSCI; Cancerlit; CINAHL; and
      Google) and the Cochrane decision aid inventory. Twenty-three met key inclusion
      criteria of (1) informing cancer screening or treatment decisions, (2) being
      patient or consumer oriented, and (3) conforming to the Cochrane definition of
      DA. DA were evaluated using the International Patient Decision Aid Standards
      checklist, the Cultural Sensitivity Assessment Tool (CSAT), the Cultural
      Sensitivity Assessment Checklist (CSAC), and the SMOG readability formula. DA had
      a high readability with 74% (n = 17) written at the grade 10 - 13, 22% (n = 5) at
      the grade 9, and 4% (n = 1) at the grade 8 level. Visual aids were used in 35% (n
      = 8) to present probability information. Written information was complemented
      with video or audio components in 35% (n = 8). Most (91%, n = 21) were developed
      for generic audiences, while 9% (n = 2) specified a cultural group. Although DA
      enabled a step-by-step movement through the website, none allowed key word
      searches and only 65% permitted document printing. Most DA included difficult
      texts and were not focused for specific cultural groups.

PMID- 18072005
TI  - Digital pens and pain diaries in palliative home health care: professional
      caregivers' experiences.
AB  - Frequent pain assessment by the use of pain diaries for the follow-up of pain
      treatment can facilitate the caregivers' work with pain control in home health
      care. The aim was to explore and describe professional caregivers' experiences of
      palliative home health-care patients' use of pain diaries and digital pen
      technology for frequent pain assessment. A system for the follow-up of pain
      treatment was implemented in routine care and evaluated by means of a qualitative
      content analysis. Three nurses, two physicians and one secretary were
      interviewed. Additional analysis data were collected from patients' medical
      records, and the system log. The caregivers showed a shifting outlook towards the
      pain-assessment method, an initial cautious outlook due to low expectations of
      the patients' abilities to use the pain assessment method. Despite this, the
      caregivers experienced positive outcomes in terms of an increased awareness of
      pain, and positive patient influences including increased participation in their
      care, increased security, and improved changes in pain treatment as a response to
      reported pain assessments. Pain assessment by the use of pain diaries and digital
      pen technology has positive influences on palliative home-care patients and
      supports the caregivers' focus on the pain.

PMID- 18072006
TI  - Assisting the transition from hospital to home for children with major congenital
      heart disease by telemedicine: a feasibility study and initial results.
AB  - Parents of children hospitalized with major congenital heart disease often state
      that the weeks following discharge from hospital are particularly difficult.
      There is a sudden change from 24-h medical supervision and care to outpatient
      reviews. Videoconferencing not only gives the family an opportunity to have
      visual and audio contact with staff but also allows clinicians to visually assess
      the patient. We have investigated the feasibility of using videoconferencing to
      provide support for families at home. We also report the early results of a
      randomized control trial comparing videoconference support with regular telephone
      support and the current clinic review follow-up.

PMID- 18072007
TI  - Patients' perceptions of Internet usage and their opportunity to obtain health
      information.
AB  - The World Wide Web is increasingly an essential resource to obtain information
      for health promotion. Coherent information is still missing as to whether
      patients' opportunities to use the Internet and to access health information have
      changed at the same time. This study examines and compares, between two different
      time periods, patients' perceptions of Internet use, to obtain health information
      and associated factors. A two-stage survey design with a non-equivalent group was
      used. The data were collected with questionnaires from hospital patients during
      their discharge process and analysed using descriptive statistics. The vast
      majority of the patients had Internet access either at home or work. The
      proportion of Internet usage increased during the study period. Patients agree on
      the importance of using technology for health-information delivery, but they
      still prefer to receive information from health-care staff by face-to-face
      contacts. Well-educated and young respondents reported more frequent access to
      the Internet.

PMID- 18072008
TI  - IgG antibodies against food antigens are correlated with inflammation and intima
      media thickness in obese juveniles.
AB  - OBJECTIVE: Systemic low grade inflammation may contribute to the development of
      obesity, insulin resistance, diabetes mellitus and atherosclerotic vascular
      disease. Food intolerance reflected by immunoglobulin G (IgG) antibodies may
      predispose to low grade inflammation and atherogenesis. We examined the
      relationship between IgG antibodies specific for food components, low grade
      inflammation and early atherosclerotic lesions in obese and normal weight
      juveniles. RESEARCH METHODS AND PROCEDURES: We determined IgG antibodies directed
      against food antigens, C-reactive protein (CRP) and the thickness of the intima
      media layer (IMT) of the carotid arteries in 30 obese children and in 30 normal
      weight children. RESULTS: Obese juveniles showed a highly significant increase in
      IMT (p=0.0001), elevated CRP values (p=0.0001) and anti-food IgG antibody
      concentrations (p=0.0001) compared to normal weight juveniles. Anti-food IgG
      showed tight correlations with CRP (p=0.001/r=0.546) and IMT (p=0.0001/r=0.513)
      and sustained highly significant in a multiple regression model. DISCUSSION: We
      show here, that obese children have significantly higher IgG antibody values
      directed against food antigens than normal weight children. Anti- food IgG
      antibodies are tightly associated with low grade systemic inflammation and with
      the IMT of the common carotid arteries. These findings raise the possibility,
      that anti-food IgG is pathogenetically involved in the development of obesity and
      atherosclerosis.

PMID- 18072009
TI  - Clinical tumor growth and comparison with proliferation markers in non
      functioning (inactive) pituitary adenomas.
AB  - BACKGROUND: As the development of clinically silent pituitary adenomas is not yet
      fully understood, the radiologically measured growth of inactive pituitary
      adenomas should be compared with adenoma classification and immunostainings for
      proliferation markers. MATERIAL AND METHODS: In 32 patients with non-functioning
      adenomas (NFA) from 45 operations with retrospectively available preoperative
      series of magnetic resonance imaging (MRI) we measured the largest growing
      diameter (LGD) in mm/ year. The adenomas were immunostained for Ki-67 (MiB-1),
      PCNA, p53 protein, IGF- and PTH-related protein. The positive nuclei for MiB-1,
      PCNA, and p53 protein were counted and their labelling indices (LI) were
      calculated. The clinical measurements were compared with these data and were
      statistically analysed (Spearman test, Whitney-U-test). The growth rate per year
      was available in 28 cases. We chosed three grades of LGD: less than 1.5 mm in
      diameter in 9 patients (32%), between 1.5 and 3.0 mm in 11 patients (39%) and
      more than 3.0 mm in 8 patients (29%). RESULTS: MiB-1 positive nuclei were found
      in 42% of adenomas, PCNA positive nuclei in 58% and p53 positive nuclei in 16%.
      IGF 1 was immuno-stained in 84% of adenomas. The mean LI for MiB-1 was 0.12 in
      adenomas growing less than 1.5 mm and 0.34 in adenomas growing more than 1.5 mm
      per year. For non-invasive adenomas, the MiB-1 LI was 0.03, for invasive adenomas
      it was 0.126 and for strongly invasive adenomas 0.212. The MiB-1 LI was lower in
      null cell adenomas than in FSH/LH adenomas. All these data for MiB-1 showed no
      statistically significant differences (p<0.05). PCNA LI in adenomas growing less
      than 1.5 mm per year was 0.51 in contrast to LI of 1.12 for those growing more
      than 1.5 mm. In non-invasive adenomas the PCNA LI was 0.796, in invasive adenomas
      0.655 and in diffuse strongly invasive ones 1.011. Null cell adenomas had a lower
      PCNA LI than FSH/LH cell adenomas. CONCLUSIONS: Statistically significant
      differences were measured for the growth rate und the PCNA expression. P53 was
      immunostained in invasive adenomas only. There were no correlations to the
      clinical growth rate, but p53 expression correlated significantly to numbers of
      MiB-1 positive nuclei and PCNA positive nuclei. IGF-I expression was found to
      correlate inversely with age of patients. We recommend the use of PCNA if
      correlations to progression of tumor growth are wanted.

PMID- 18072010
TI  - Microscopic, morphometric and ultrastructural analysis of anastomotic healing in
      the intestine of normal and diabetic rats.
AB  - The purpose of this study was to investigate if experimental alloxanic diabetes
      could cause qualitative changes in intestinal anastomoses of the terminal ileum
      and distal colon in rats, as compared to controls. 192 male Wistar rats, weighing
      +/-300 g were split into four experimental groups of 48 animals each, after 3
      months of follow-up: a control group with ileum anastomoses (G1), a control group
      with colon anastomoses (G2), a diabetic group with ileum anastomoses (G3) and a
      diabetic group with colon anastomoses (G4). Animals were evaluated and sacrificed
      on days 4, 14, 21 and 30 after surgery, and fragments of the small and large
      intestine where the anastomoses were performed were removed. Samples from 6
      animals from each sacrifice moment were submitted to ultrastructural analysis of
      the collagen fibers using a scanning electron microscope and samples from another
      6 animals were submitted to histopathology and optical microscopy studies using
      picrosirius red-staining. Histopathological analysis of picrosirius red-stained
      anastomosis slides using an optical microscope at 40x magnification showed that
      the distribution of collagen fibers was disarranged and also revealed a delay in
      scar tissue retraction. The morphometric study revealed differences in the
      collagen filled area for the ileum anastomoses 14 days post surgery whereas, in
      the case of colon anastomoses, differences were observed at days 4 and 30 post
      surgery, with higher values in the diabetic animals. Ultrastructure analysis of
      the ileum and colon anastomoses using a scanning electron microscope revealed
      fewer wide collagen fibers, the presence of narrower fibers and a disarranged
      distribution of the collagen fibers. We conclude that diabetes caused qualitative
      changes in scar tissue as well as in the structural arrangement of collagen
      fibers, what could explain the reduced wound strength in the anastomosis of
      diabetic animals.

PMID- 18072011
TI  - Painless self-monitoring of blood glucose at finger sites.
AB  - INTRODUCTION: Skin punctures at alternative sites can reduce the pain associated
      with self-monitoring of blood glucose (SMBG). However, delays in detection of
      blood glucose at alternative sites during rapid systemic blood glucose change
      have been reported. Accordingly, we developed a novel method of finger pricking
      and tested it to see if it would both reduce or eliminate pain and accurately
      reflect systemic glucose levels, even during rapid changes. METHODS: Each of 35
      healthy volunteers (10 females and 25 males; mean age 36.6 years, range 18-82
      years) received 5 serial punctures from a lancet device on randomly selected
      fingers. The puncture target was the dorsal side of the finger between the nail
      and the distal finger joint. We used a lancet device designed for accurate
      punctures of 0.2, 0.3, 0.4, 0.5 and 0.6 mm depths. Immediately afterward, as a
      control, a conventional fingertip puncture was done on the front of a 6th finger.
      After each puncture, subjects were asked whether or not they felt pain. RESULTS:
      Following punctures at depths of 0.2 mm and 0.3 mm, respectively, 31 of 35
      subjects (89%) and 33 of 35 subjects (94%) felt no pain. Following conventional
      punctures, all 35 subjects (100%) felt pain. Blood sample volumes> or =2microL
      were obtained in all cases except for two punctures at 0.2 mm depth. Blood
      glucose levels did not differ with differing puncture sites, (conventional
      fingertip sites vs. alternative sites used in this study). CONCLUSIONS: Our
      findings demonstrate that 0.2 and 0.3 mm punctures at our alternative finger site
      - the dorsal side of the finger between the nail and the distal finger joint -
      can provide blood samples sufficient for SMBG, substantially redu-ces the
      proportion of subjects who experience pain, and accurately reflects systemic
      glucose levels.

PMID- 18072012
TI  - Genetic variation of Neurogenin 3 is slightly associated with
      hyperproinsulinaemia and progression toward type 2 diabetes.
AB  - OBJECTIVE: Transcription factor Neurogenin 3 (NGN3) is considered as a candidate
      gene for the development of type 2 diabetes. The aim of the current study was to
      investigate the relevance of NGN3 variants for the clinical spectrum of diabetes
      development and disease progressions. RESEARCH DESIGN AND METHODS: A total of 552
      subjects with increased risk of type 2 diabetes were investigated. They underwent
      a 75 g OGTT with measurements of plasma glucose, insulin and proinsulin at
      fasting and at 30, 60, 90 and 120 minutes after the glucose challenge, repeated
      after 3 years. The NGN3 SNPs, Gly167Arg and Ser199Phe were genotyped. RESULT:
      Patients with type 2 diabetes carrying the variant genotype at SNP199 presented
      with significantly higher proinsulin levels. Proinsulin level was also associated
      with progression of diabetes mellitus. There was a discrete association of the
      Ser199Phe variant with evolution of the disease status. CONCLUSION: A genetic
      variation in NGN3 gene may be among the genetic determinants involved in the
      pathogenesis of diabetes.

PMID- 18072013
TI  - Serum levels of receptor activator of nuclear factor kappaB ligand (RANKL) in
      healthy women and men.
AB  - BACKGROUND: Osteoporosis is one of the most common conditions associated with
      aging. It is based on an excess of bone resorption over bone formation, leading
      to an imbalance of bone turnover. The receptor activator of nuclear factor kappaB
      ligand (RANKL) is an important regulator of bone metabolism. OBJECTIVE: The aim
      of this investigation was to evaluate potential age- and gender-related changes
      in free RANKL and total RANKL (free RANKL+RANKL/osteoprotegerin complexes).
      METHODS: Two hundred and forty volunteers with a median age of 48 years were
      included in the study. Serum levels of free RANKL and total RANKL were evaluated.
      RESULTS: On average, men have a 1.77-fold higher free RANKL level and a 2.12-fold
      higher free/total RANKL ratio than women of the same age. On average, the RANKL
      levels decrease by approximately 13% every five years. CONCLUSION: This study
      showed that serum levels of free RANKL and total RANKL decrease with age, and
      also revealed some gender-related differences.

PMID- 18072014
TI  - Goiter persistence after iodine replenishment, the potential role of selenium
      deficiency in goitrous schoolchildren of Semirom, Iran.
AB  - BACKGROUND: Despite long-standing iodine supplementation in Iran, the prevalence
      of goiter remains high in some areas. This suggests other nutritional
      deficiencies may be considered as responsible factors of goiter persistence.
      Therefore, we assessed the prevalence of selenium deficiency in children living
      in a mountainous area in Iran to evaluate its correlation with goiter. METHODS:
      In this cross-sectional study, 1828 students from the 108 primary schools of
      urban and rural areas of Semirom in central Iran were selected by multistage
      random cluster sampling. After obtaining written consent from their parents, the
      children were examined for goiter grading. Grade 2 goitrous children (108 cases)
      were compared with non-goitrous children (111 children) as control group for
      serum selenium concentration. RESULTS: Overall, 36.7% of 1828 students had
      goiter. The mean and median urinary iodine excretion level was 19.3 and 18.5
      mug/dl respectively. This was within normal limits. Of 219 evaluated cases, 109
      children had selenium deficiency. Mean serum levels of selenium in the goitrous
      and control groups were 62.7 mug/l and 60.8 mug/l, respectively (p=0.42). There
      was a borderline significant difference of the goiter prevalence in selenium
      deficient and selenium sufficient subjects (40.8% vs. 54.3%, p=0.037). Twelve
      children had clinical or subclinical hypothyroidism. The mean (SD) serum selenium
      concentration of euthyroid and hypothyroid students were 61.9 (17.2) mug/l and
      66.4 (11.9) mug/l respectively (p=0.35). CONCLUSION: In the area studied,
      selenium deficiency cannot explain high prevalence of goiter and other
      responsible factors should be investigated. Selenium deficiency may also have
      mild borderline significant protective effects on thyroid function and goiter.

PMID- 18072015
TI  - The DG10S478 variant in the TCF7L2 gene is not associated with microvascular
      complications in type 2 diabetes.
AB  - OBJECTIVE: The DG10S478 variant in the transcription factor 7-like 2 (TCF7L2)
      gene is a tetranucleotide repeat with six alleles. Alleles 0, 8 and 12 were found
      to account for 98% of chromosomes in population based controls. The composite
      allele X (non zero) has been associated with type 2 diabetes while allele 0 (no
      insertion) was described as protective. However, no data exist about the
      influence of DG10S478 variants on manifestation of diabetes and development of
      diabetic complications. METHODS: 250 patients with type 2 diabetes were tested
      for the DG10S478 allele X and its association with diabetic complications, age at
      diagnosis of diabetes and BMI. RESULTS: Allele 0 was found in 42.4% of the
      examined patients, 45.2% of the participants were found to be heterozygous and
      12.4% homozygous for the composite allele X. The correlation of allele X with the
      age at diagnosis of diabetes was not significant. There was also no association
      of allele X with retinopathy, nephropathy or neuropathy. Only the correlation
      with BMI was statistically significant. CONCLUSIONS: The DG10S478 variant seems
      to have no influence on manifestation of diabetes and the development of
      microvascular complications.

PMID- 18072016
TI  - SREBP-1c gene polymorphism is associated with increased inhibition of cholesterol
      absorption in response to ezetimibe treatment.
AB  - OBJECTIVE: Sterol regulatory binding proteins 1 and 2 (SREBPs) are transcription
      factors regulating lipid metabolism. A recent study has associated the CC
      genotype of the SREBP-1c polymorphism G952G with increased cholesterol synthesis.
      Further evidence suggests that SREBPs play a role in cholesterol absorption and
      that SREBP polymorphisms modulate the response to statin therapy. The present
      study examines whether the G952G polymorphism alters cholesterol synthesis and/or
      absorption and whether it modulates the response to widely used lipid-lowering
      drugs such as inhibitors of cholesterol synthesis (simvastatin) or absorption
      (ezetimibe). METHODS: Seventy-two healthy male subjects with LDL cholesterol <190
      mg/dL participated in the study. Twenty four subjects were treated with ezetimibe
      (10 mg), simvastatin (40 mg) or their combination, respectively, for two weeks.
      Blood was drawn before and after the 2-week treatment period. RESULTS: Eleven CC
      homozygous carriers of the gene were found (15%). There were no differences in
      cholesterol synthesis or absorption between the CC homozygotes and the G allele
      carriers, as measured by the ratios to cholesterol of serum lathosterol,
      desmosterol and cholestenol (synthesis markers) and cholestanol, sitosterol and
      campesterol (absorption markers). Ezetimibe had a significantly more potent
      effect in blocking cholesterol absorption in the CC homozygotes compared to the G
      carriers ( P=0.002). CONCLUSIONS: The G/C (G952G) polymorphism of the SREBP-1
      gene is not associated with cholesterol synthesis or absorption in a German male
      population. The CC homozygotes have a significantly increased response to the
      effects of ezetimibe on cholesterol absorption compared to the G allele-carriers,
      suggesting that SREBP-1 may be implicated in ezetimibe's mechanism of action.

PMID- 18072017
TI  - Adipose triglyceride lipase gene expression in human visceral obesity.
AB  - In comparison to subcutaneous (SC) fat, visceral adipose tissue is more sensitive
      to catecholamine-induced lipolysis and less sensitive to the antilipolytic
      effects of insulin. Variation in the expression of lipoprotein lipase (LPL) and
      hormone-sensitive lipase (HSL) have been reported. We therefore hypothesized that
      expression of adipose triglyceride lipase (ATGL) is different in visceral and SC
      depot and investigated whether ATGL mRNA expression is related to obesity, fat
      distribution and insulin sensitivity. ATGL, LPL, and HSL mRNA expression was
      measured in 85 paired samples of omental and subcutaneous adipose tissue in
      normal glucose tolerant lean and obese individuals. In addition, we included a
      subgroup of obese (BMI >30 kg/m2) individuals with either impaired or preserved
      insulin sensitivity determined by euglycemic-hyperinsulinemic clamps. ATGL mRNA
      levels are significantly decreased in insulin resistant obese subjects.
      Independently of body fat mass, omental ATGL mRNA correlates with fasting insulin
      concentration, glucose uptake during the steady state of the clamp and HSL mRNA
      expression. In obese, but not in lean subjects, LPL and HSL mRNA expression was
      significantly higher in omental compared to SC fat. In both depots, HSL mRNA was
      significantly lower in obese individuals. Visceral HSL mRNA expression is closely
      related to adipocyte size and fasting plasma insulin concentrations, whereas
      visceral fat area significantly predicts visceral LPL mRNA expression. ATGL mRNA
      expression is not significantly different between omental and SC fat. HSL, but
      not ATGL mRNA expression is closely related to individual and regional
      differences in adipocyte size. Impaired insulin sensitivity was associated with
      decreased ATGL and HSL mRNA expression, independently of body fat mass and fat
      distribution.

PMID- 18072019
TI  - 48-hour wireless oesophageal pH-monitoring in children: are two days better than
      one?
AB  - BACKGROUND: Use of a catheter-free, radio telemetric, oesophageal pH-monitoring
      system in paediatric clinical practice allows patients to follow a more normal
      physiological pattern of activities and causes less discomfort. At our
      institution, placement of the capsule is done under general anaesthesia, which
      restricts the child's activity during the first day. The aim of this study was to
      determine whether oesophageal pH-measurements should be performed over 48 hours
      or whether 24-hour measurement provides sufficient and reliable results. CHILDREN
      AND METHODS: The study included 24 consecutive children with symptomatic gastro
      oesophageal reflux problems who had undergone upper gastrointestinal endoscopies
      under general anaesthesia. The radio-transmitting Bravo capsule was introduced
      transorally and placed above the diaphragm at a width of two vertebral bodies.
      Oesophageal acid exposure was monitored via a portable receiver for 48 hours. The
      children's symptoms during measurements were registered. Wilcoxon signed rank
      test for paired samples was used after power analysis. RESULTS: The capsule was
      successfully attached to the oesophageal mucosa in all cases with minor technical
      problems in only one patient. The 48-hour pH-monitoring was completed in 23
      patients. The median percentage time with an oesophageal pH of less than 4 was
      5.4 +/- 6.8 for the first 24 hours and 5.8 +/- 7.4 for the 48-hour measurement.
      The DeMeester score was 20.5 +/- 23.7 and 22.2 +/- 25.7, respectively.
      CONCLUSIONS: Ambulatory pH-monitoring using the wireless system is feasible and
      safe. It was well-tolerated by the children. There was no statistical difference
      between the pH-measurements or DeMeester scores during the first 24 hours
      compared with the 48-hour measurements. Individual variations were noted but had
      no clinical significance except in two patients. Our results support the use of
      pH-measurement for a period of 24 hours only.

PMID- 18072020
TI  - Compensatory renal growth in children with unilateral renal tumor treated by
      nephron-sparing surgery or nephrectomy.
AB  - INTRODUCTION: In children with an unilateral renal tumor, nephron-sparing surgery
      (NSS) results in a more adequate renal function adaptation compared to
      nephrectomy. In the present study, we investigated whether nephron-sparing
      surgery is followed by a different renal structure adaptation compared to
      nephrectomy. METHODS: Sixteen patients with unilateral renal tumor treated by
      nephrectomy (Group 1) and 10 treated by nephron-sparing surgery (Group 2) were
      enrolled in the study. Kidney volume was estimated by ultrasonography, using the
      formula for a prolate ellipsoid. Kidney volume was adjusted to the patient's
      weight and kidney laterality and expressed as a percentage of the expected volume
      of two kidneys in a healthy child. Total kidney volume (TKV) corresponded to the
      volume of the contralateral kidney in Group 1 patients, and to the volume of
      contralateral kidney + kidney remnant in Group 2 patients. Renal function was
      evaluated by serum creatinine values adjusted for sex and age and expressed as
      standard deviation scores (SDS). RESULTS: Group 2 patients presented with a
      greater indexed TKV compared to Group 1 patients, (97.4 +/- 18.8 % vs. 77.0 +/-
      17.7 %; p = 0.005). Indexed TKV below the reference range for healthy controls
      with two kidneys was found in 4 of 10 Group 2 patients vs. 14 of 16 Group 1
      patients (p = 0.017). In both patient groups, correlation analysis of indexed TKV
      and creatinine SDS showed a negative correlation (r = - 0.47; p = 0.01).
      CONCLUSION: In children with unilateral renal tumor, NSS is followed by a more
      adequate compensatory restoration of TKV compared with nephrectomy.

PMID- 18072021
TI  - Surgery of liver tumors in children in the last 15 years.
AB  - AIM: Aim of the study was to review our experience in the management of liver
      tumors in children over the last 15 years. PATIENTS AND METHODS: A cohort of 78
      children with liver tumors managed in our institution between 1991 and 2006 was
      retrospectively reviewed. There were 45 males and 33 females with a mean age of
      32 +/- 41 months at diagnosis. Most tumors were malignant (n = 57); the most
      frequently occurring tumor was hepatoblastoma (n = 47), followed by
      hepatocarcinoma (n = 5), sarcoma (n = 4), and lymphoma (n = 1). Vascular tumors
      (n = 12) predominated among the benign tumors followed by mesenchymal hamartoma
      (n = 4), focal nodular hyperplasia (n = 3), adenoma (n = 1), and inflammatory
      pseudotumor (n = 1). We reviewed the epidemiologic features, clinical
      presentation, diagnosis, treatment and outcomes. We employed MRI and angio-CT for
      SIOPEL PRETEXT staging and selected the management accordingly for malignant
      tumors. We analyzed the long-term survival using Kaplan-Meier curves. RESULTS:
      Benign tumors had an excellent outcome with both medical or surgical management.
      Of the malignant tumors 4 were PRETEXT I and were treated by left lateral
      segmentectomy with 100 % survival; 20 were PRETEXT II (12 left and 8 right lobe)
      and were treated by lobectomy of the corresponding side, except for 1 case which
      required OLT (90 % survival); 9 children had PRETEXT III tumors requiring
      trisegmentectomy or extended lobectomies with OLT in 1 case (77.7 % survival).
      Fourteen children had PRETEXT IV tumors: 10 received OLT and 9 of them are still
      alive (64.2 % survival). Overall survival was 80.8 %, and actuarial survival at 6
      years was 82.2 %. Other malignant tumors had variable results. CONCLUSIONS:
      Outcomes have improved much in the last years. Surgical removal is necessary in
      most cases. Transplantation is a very useful adjunct. Treatment of these tumors
      should be concentrated in centers with expertise.

PMID- 18072022
TI  - Bilateral adrenal neuroblastoma is different.
AB  - BACKGROUND/AIMS: Bilateral adrenal neuroblastoma is rare and can be due to
      multifocal primary or contralateral metastasis. Staging is confusing in these
      patients and treatment guidelines are difficult to set. The present study
      examines the clinical, biological and therapeutic features of bilateral adrenal
      neuroblastoma. METHODS: We identified 4 cases primarily located in both adrenals
      out of 148 neuroblastomas treated between 1992 and 2006. We studied the
      clinicopathological findings and biological features, including MYCN
      amplification, and analyzed the treatment strategies and results. RESULTS: All
      patients were younger than 6 months of age and all had multiple liver metastases.
      Three had subcutaneous nodules and massive liver enlargement. All underwent
      chemotherapy prior to operation. Two babies had large bilateral tumors without
      preservable glands and underwent bilateral adrenalectomy. Both had MYCN gene
      amplification and died of widespread (brain and bone) metastases some weeks
      later. In the remaining two patients adrenalectomy was performed on the side of
      the larger tumor with tumor enucleation on the other side to preserve hormonal
      function followed by 2 courses of mild chemotherapy in one patient. These tumors
      were not amplified. Both of these children are doing well. CONCLUSIONS: Bilateral
      adrenal neuroblastomas fit neither into stage 4 s nor into stage 4. Their
      clinical behavior is exceptional with a number of multicystic forms, variable
      MYCN amplification, widespread metastases and a high mortality. Bilateral
      adrenalectomy is sometimes unavoidable, but unilateral removal with contralateral
      enucleation, partial resection or observation are valid alternatives. Mortality
      is higher than in regular stage 4 s cases. This particular group of
      neuroblastomas required individually tailored therapeutic strategies based on the
      size, extent and prognostic markers.

PMID- 18072023
TI  - Umbilical polyp in infants and children.
AB  - AIM OF THE STUDY: The umbilical polyp is a rare congenital lesion resulting from
      the persistence of omphalomesenteric duct (OMD) enteric mucosa at the umbilicus.
      Exploration of the abdomen to exclude the presence of associated OMD remnants is
      controversial. The aim of this study was to evaluate the need for peritoneal
      cavity exploration in children with umbilical polyp. METHODS: All umbilical
      lesions (n = 53) excised between 1995 and 2005 in a single institution were
      reviewed to identify patients with umbilical polyp (n = 13). This is
      characterised histologically by the presence of gastrointestinal mucosa. A follow
      up study of patients with umbilical polyp was performed. Data are reported as
      median (range). RESULTS AND CONCLUSIONS: All 13 patients underwent excision of an
      umbilical polyp at a median age of 15.1 months (3.1 - 80.5). All presented with a
      discharging polyp (associated with bleeding in 9) which did not respond to
      topical silver nitrate. Median diameter of the lesions was 0.5 cm (0.2 - 1).
      Histology revealed the presence of small bowel mucosa in 11 (associated with
      pancreatic tissue in 1 and gastric mucosa in 1) and large bowel mucosa in 2. All
      patients underwent inspection and probing of the base of the polyp after its
      excision. In 6 patients an associated OMD anomaly was suspected and exploration
      of the peritoneal cavity was performed (mini-laparotomy in 5 and laparoscopy in
      1). No OMD anomaly was found. The 7 children who did not undergo exploration of
      the abdominal cavity remain asymptomatic after 5.8 years (0.9 - 13.7) follow-up.
      An umbilical polyp can be present in the absence of other OMD anomalies.
      Exploration of the peritoneal cavity in children with an umbilical polyp does not
      seem to be necessary.

PMID- 18072024
TI  - Management of hydatidosis in children. Twenty-one year experience.
AB  - PURPOSE: Hydatidosis is a serious problem in non-endemic countries due to the
      influx of immigrants from nations where preventive measures are inadequate. The
      aim of this retrospective study is to present our experience in the management of
      hydatidosis in children and to define the criteria for the most effective model
      of treatment. MATERIAL AND METHODS: Over a 21-year period (1985 - 2006), 150
      children with pulmonary and abdominal hydatidosis (ECHINOCOCCUS CYSTICUS) were
      treated at our department. The anatomical location of the parasite was as
      follows: liver 82, lungs 59, spleen 4, mesentery 2, kidneys 2 and pelvic floor 1
      case. Medical treatment with oral antihelminthic agents was given to 37 patients
      (45.1 %), with liver hydatidosis, 36 patients (61 %) with pulmonary hydatidosis
      and one patient with hydatid cyst of the spleen. The remaining 76 patients were
      submitted primarily to excision of the cyst or partial capsectomy. RESULTS:
      Medical treatment was ineffective in 16 patients (43.2 %) with liver hydatidosis,
      11 patients (30.6 %) with pulmonary hydatidosis and one patient with hydatidosis
      of the spleen. All patients with pulmonary hydatidosis who failed to respond to
      medical treatment developed complications requiring surgical intervention. Of the
      76 patients who were submitted to surgery initially, only 4 (5.3 %) presented
      with postoperative complications requiring reoperation. In all cases who
      responded inadequately to medical treatment or developed complications the cyst
      diameter exceeded 6 cm. The overall long-term results were good. CONCLUSIONS: a)
      Hydatid cysts with sizes exceeding 6 cm in diameter should not be treated
      medically; b) medical treatment seems to be more effective for pulmonary
      hydatidosis but failed medical treatment in these patients leads to complications
      with increased morbidity; c) large hydatid cysts should be treated surgically
      from the start.

PMID- 18072025
TI  - Impact of fetal intervention on postnatal management of congenital diaphragmatic
      hernia.
AB  - We report our experience in the postnatal management of congenital diaphragmatic
      hernia (CDH) after fetal endoluminal balloon tracheal occlusion (FETO). MATERIAL
      AND METHODS: Out of 19 CDH fetuses diagnosed since December 2005, 13 had a lung
      to-head ratio (LHR) < 1.1 (0.86 +/- 0.11) and underwent FETO at a mean
      gestational age (GA) of 27.9 weeks. The balloon was removed in 3 cases through
      puncture in EXIT (ex utero intrapartum treatment); there were 3 trans-utero
      punctures, 3 fetoscopies and 3 balloons deflated spontaneously. One patient died
      from bleeding during the FETO procedure. Six patients were not subjected to FETO:
      3 had a LHR > or = 1.4 and 3 did not come to consultation prenatally. RESULTS:
      Twelve babies were born after FETO at 34.9 +/- 1.7 weeks GA; 3 died before
      surgery from refractory hypoxia. Six needed high frequency oscillatory
      ventilation (HFOV), and inhaled nitric oxide (NO), one progressing to
      extracorporeal membrane oxygenation (ECMO), and 3 needed conventional
      ventilation. CDH was repaired in 9: 2 with direct sutures and 7 with prosthetic
      patches. Extubation was at median of 5 days (range: 2 - 40), discharge was at
      30.4 +/- 16.4 days. Early complications were 1 reherniation and 2 intestinal
      occlusions. Two patients died after CDH repair: the ECMO case at 15 days, and an
      infant discharged on oxygen at home, at age 4 months. Of the non-FETO patients,
      four needed HFOV and NO. CDH repair was performed in 5: 3 had direct repair and 2
      had prosthetic patches. Extubation was at 13.4 +/- 12.9 days and discharge was at
      43.8 +/- 26.5 days. One patient died before surgery from severe cardiac
      malformation. Early complications were 1 reherniation and 1 hiatus hernia. Late
      complication was 1 reherniation at 5 months of life. There was no postoperative
      mortality. One patient needs oxygen at home. CONCLUSION: CDH patients with a poor
      prognosis undergoing FETO had postnatal outcomes similar to non-prenatally
      studied cases and good prognosis cases.

PMID- 18072026
TI  - Evaluation and treatment for spinal cord tethering in patients with anorectal
      malformations.
AB  - BACKGROUND: It has recently been recognized that there is a close relationship
      between spinal cord tethering (SCT) and congenital anorectal malformation (ARM).
      PATIENTS AND METHODS: We evaluated spinal MRI examinations of 28 patients with
      ARM (14 boys and 14 girls) aged 5 months to 9 years. All patients diagnosed with
      SCT subsequently underwent operation. Patients were divided into high and low
      type ARM groups. We reviewed the relationship between SCT and ARM, and evaluated
      the untethering surgery. RESULTS: We evaluated 14 boys (high, 9; low, 5) and 14
      girls (high, 4; low, 10). Of these 28 patients, 13 had SCT on MRI. Five out of 13
      patients with high type ARM and 8 out of 15 patients with low type ARM had SCT.
      Seven out of 10 girls with low type ARM had SCT. Ten of these 13 patients with
      SCT experienced bowel/urological/orthopedic symptoms. SCT symptoms progressed
      prior to operation in the 2 patients who underwent untethering surgery a few
      years after their initial MRI examination. Postoperatively, orthopedic symptoms
      disappeared completely in all patients, but other symptoms did not. CONCLUSIONS:
      Based on the results of this study, we recommend routine MRI examination of
      patients with ARM and early untethering surgery in cases with SCT.

PMID- 18072027
TI  - Prognostic value of skin histology in GVHD after intestinal transplantation.
AB  - Intestinal transplantation (Itx) is increasingly being performed to treat
      patients with irreversible intestinal failure. Acute graft-versus-host disease
      (GVHD) after Itx is a life-threatening complication which can progress to organ
      failure, systemic complications and death. The purpose of this study was to
      assess the diagnostic and prognostic role of histological changes as demonstrated
      by skin biopsy for acute GVHD after Itx. A porcine model of orthotropic Itx and
      bone marrow transplantation with tacrolimus-based immunosuppression was used to
      assess any correlation between acute graft cellular rejection and skin
      histological findings for the prediction of GVHD. Skin and small intestinal
      biopsies were histologically assessed on postoperative days 0, 15, 30, 45, and 60
      and analyzed and classified as grade 1 to 4. A linear correlation was observed
      between the histological grading values of skin biopsy changes and the
      histological grading values of small intestinal biopsy changes (Kendall's tau_b
      was 0.855 for the Itx group and 0.730 for the Itx BM group. In conclusion, our
      findings emphasize the diagnostic and prognostic value of skin biopsy analysis
      for acute GVHD after Itx.

PMID- 18072028
TI  - Intestinal prostaglandin E2 expression in rats with obstructive jaundice.
AB  - AIM: How obstructive jaundice causes the intestinal barrier to be injured is
      still controversially discussed. In this study, we hypothesize that intestinal
      prostaglandin E (2), a cytoprotective factor, may be affected by the bile duct
      obstruction. MATERIALS AND METHODS: Four groups of Wistar-Albino rats were used:
      in Groups 1 and 3, the rats underwent a sham operation. In Groups 2 and 4, the
      common bile duct was doubly ligated. Relaparotomy was performed after one week in
      Groups 1 and 2, and after two weeks in Groups 3 and 4, and specimens of the
      jejunum, ileum and liver were obtained for intestinal PGE (2) analysis and
      histopathological evaluation. RESULTS: Jejunal and ileal PGE (2) levels had
      significantly decreased in two-week bile duct-ligated rats compared to one-week
      ligated rats and the sham group (p < 0.01). Tissue injury scores (Chiu score) of
      the ileum were significantly higher in the two-week and one-week ligated rats
      than in the controls (p < 0.01 and p < 0.05, respectively). The jejunal injury
      score was significantly higher in the two-week ligated rats compared to controls
      (p < 0.05). The ileal and jejunal injury scores were higher in the two-week
      ligated rats than in the one-week ligated rats (p < 0.01 and p < 0.05,
      respectively). Precirrhotic fibrosis was detected in all two-week ligated rats,
      but in only 7 of 10 one-week ligated rats. CONCLUSIONS: Obstructive jaundice
      associated with intestinal tissue injury and precirrhotic changes leads to
      reduced intestinal PGE (2)-levels, suggesting an adverse effect on the intestinal
      cytoprotective process.

PMID- 18072029
TI  - Immune response to xenogeneic matrix grafts used in pediatric surgery.
AB  - BACKGROUND: Lyoplant is an acellular, bovine derived extracellular matrix (ECM)
      that has been used for tissue remodelling and repair in numerous
      xenotransplantations. The aim of our study was to evaluate the inflammatory
      response and tensile strength after xenogeneic matrix (Lyoplant) implantation
      compared to the more widely used synthetic polypropylene matrix. METHODS: Full
      thickness abdominal wall defects were created in 15 Wistar WU rats and
      reconstructed with either a Lyoplant matrix (B. Braun Aesculap, Tuttlingen,
      Germany) or a Prolene matrix (a polypropylene matrix [PPP]; Prolene, Ethicon,
      Norderstedt, Germany). Animals in both the treatment and the control groups were
      checked daily for local and systemic complications. Bodyweight was recorded and
      the possible development of a hernia was monitored. After 6 weeks the abdomen was
      reopened and adhesions to the intestine were determined. Histopathology and
      immunohistochemistry were performed to evaluate the immunological reaction to the
      xenograft. RESULTS: Compared to the untreated animals, all rats had a
      physiological growth and bodyweight curve: No wound infection was observed during
      the experiment. An abdominal hernia developed at the implant site only in one rat
      treated with a PPP matrix. All other animals had an excellent clinical recovery
      and good cosmetic results. PPP animals showed a pronounced inflammatory response
      indicated by an increased number of fibroblasts. The Lyoplant matrix implantation
      induced an infiltration of CD4 and CD68 positive cells. In addition, active
      neovascularization was found, indicating a remodelling process. The inflammatory
      response in Lyoplant treated animals was significantly milder than in PPP
      implanted rats. Interestingly, some CD8 positive cells were detected in the
      Lyoplant group. CONCLUSION: A xenogeneic extracellular matrix, such as Lyoplant,
      may induce an immune response which is predominantly TH2-like and comparable with
      a remodelling reaction rather than rejection.

PMID- 18072030
TI  - Beware of stapled side-to-side bowel anastomoses in small children.
AB  - Side-to-side, functional end-to-end stapled anastomosis (SS-EESA) is a frequently
      employed technique to re-establish continuity following bowel resection. We
      describe, for the first time in children, two cases of an important complication
      of this form of bowel anastomosis. Patient 1 had resection of a jejunal
      lymphangioma and formation of an SS-EESA at the age of 3 years. By the age of 7
      years he was demonstrating symptoms consistent with malabsorption, which was
      confirmed by hydrogen breath testing. An upper GI contrast study indicated a
      segmental dilatation of the distal small bowel. Elective laparotomy revealed
      partial volvulus of a greatly dilated SS-EESA. Patient 2 had undergone bowel
      resection as a neonate for ileal atresia, with end-to-end anastomosis. An
      anastomotic stricture developed at two months of age that was resected with
      formation of an SS-EESA. Multiple ensuing episodes of partial small bowel
      obstruction were managed non-operatively until, at 5 years of age, she presented
      with complete bowel obstruction. At operation, volvulus of a hugely dilated SS
      EESA was found. Intraoperative cultures of the succus entericus were consistent
      with bacterial overgrowth. Both patients were successfully treated with resection
      of the SS-EESA and primary anastomosis. SS-EESA can be complicated by bacterial
      overgrowth, massive dilatation and volvulus. In patients with SS-EESA who present
      with recurrent obstructive symptoms, this complication should be considered.

PMID- 18072031
TI  - Penile malignant peripheral nerve sheath tumour (schwannoma) in a three-year-old
      child without evidence of neurofibromatosis.
AB  - Malignant schwannoma (malignant peripheral nerve sheath tumour, MPNST) is a rare
      high-grade tumour arising from peripheral nerves. We report the case of a 3-year
      old male who presented with a non-tender lesion on the dorsum of his penis. The
      lesion was excised and a formal circumcision performed. Histology of the lesion
      revealed a spindle cell tumour. Immunohistochemistry showed the tumour cells to
      be strongly positive for S100 and Vimentin. A diagnosis of intermediate grade
      malignant peripheral nerve sheath tumour was made. Malignant schwannoma is rare
      in children and is previously unreported in the penis in the paediatric age group
      without evidence of neurofibromatosis.

PMID- 18072032
TI  - OK-432 as a sclerosing agent to treat wound-healing impairment.
AB  - We report on the application of OK-432 (picibanil) in a patient with prolonged
      wound healing impairment. A 13-year-old girl had suffered a polytrauma with a
      displaced fracture of the sacrum which required neurosurgical decompression of
      the sacral plexus. Postoperatively, a seroma with recurrent fistulation was seen.
      Excision of the wound, prolonged suction drainage and the instillation of
      hypertonic glucose solution did not have any effect over a period of four months
      postoperatively. Relying on our personal experience of the treatment of
      lymphangiomas using OK-432 we instilled OK-432 into the wound. Leakage stopped
      immediately, there was a regression of fluid accumulation and four weeks later
      the ultrasound examination was normal. The patient is still asymptomatic four
      years after treatment. OK-432 can be used effectively for the treatment of
      chronic wound healing impairment.

PMID- 18072033
TI  - Letter to the editor from the President of the EUPSA. Perspectives on paediatric
      surgery in Europe in the 21st century.

PMID- 18072034
TI  - [Cruciate ligament reconstruction].

PMID- 18072035
TI  - [Results of ACL reconstruction with a periost-patella tendon-periost graft in
      growth age].
AB  - AIM: The results of 16 patients in growth age (mean age at surgery 13.7 years)
      with an ACL rupture that was treated with an ACL reconstruction using an periost
      patella tendon-periost graft were reviewed. RESULTS: The follow-up was done 12
      months postoperatively. All patients were satisfied with the result of the
      surgery. No leg length differences or abnormalities of the axis were found. 14
      patients had already regained their original sports level. In the Tegner score,
      an average level of 8 was reached and a mean of 97 points in the Lysholm score.
      In the IKDC score we found a level of A (normal) 9 times and of B (nearly normal)
      7 times. CONCLUSION: These follow-up examinations show that the treatment of an
      ACL rupture in growth age with a periost-patella tendon-periost graft leads to
      good results. It is a good alternative to the other methods (e.g.,
      semitendinosus). Today, it can be regarded as a standard that an ACL rupture with
      open growth plates should be treated operatively.

PMID- 18072036
TI  - [One- and two-stage procedure for revision after failure of anterior cruciate
      ligament reconstruction].
AB  - AIM: Most surgeons favour a one-stage procedure for ACL revision surgery. Tunnel
      widening, limited range of motion or existent hardware can make a two-stage
      procedure necessary. Studies evaluating the results between both procedures are
      still lacking. Thus, we performed a prospective preliminary study comparing early
      results after one- and two-stage procedures for ACL revision reconstruction.
      METHOD: Between 1/2005 and 1/2006 21 patients were operated on for ACL revision.
      The follow-up period of the 4 women and 16 men was 12 months. One patient was
      excluded due to a juvenile osteoporosis. Median age was 34 years. All patients
      had a subjective instability, including 11 patients (55%) with a traumatic
      rerupture. The indication for a two-stage procedure depended on tunnel widening
      under consideration of tunnel placement, disturbing existing hardware and
      extension deficits. Eleven patients received a one-stage procedure while 9
      patients were operated in a two-stage process. Seven received autogenous bone
      grafting. RESULTS: The preoperative tunnel diameter was for one-stage revisions
      (OS) femoral 7.9 +/- 1.8 mm and tibial 8.8 +/- 2.2 mm. For the two-stage (TS)
      procedure mean femoral tunnel was preoperatively 10.1 +/- 1.4 mm and tibial 12.1
      +/- 1.4 mm. Femoral tunnel placement after revision (OS/TS) yielded a mean angle
      in anteroposterior view of 28.7 degrees /26.9 degrees and in the sagittal view
      most tunnels were placed in the dorsal quadrant. Tibial placement was in the
      sagittal view at 46.1%/46.9% in the anteroposterior direction and for
      mediolateral direction in the a. p. view at 44.2%/44.5%. Results for Lysholm
      score were 85.7/83.9 and for IKDC 73.6/76.4. The anterior tibial translation
      compared to the healthy side was 1.5 mm/1.8 mm. In one leg jumping patients
      obtained a distance of 83 %/86% of the healthy side and stated their pain on a
      VAS to be as low as 1.9/1.4 points. Both groups had similar ranges of motion as
      well. CONCLUSION: The success of ACL revision surgery crucially depends on
      preoperative planning and analysis. No functional or radiological differences
      could be observed between one- and two-stage procedures. Although the one-stage
      procedure might be favourable because of faster convalescence and shorter work
      incapacity, it should not be enforced at the price of an insufficient ACL.

PMID- 18072037
TI  - [Radiological and clinical functional examinations 36 months after anterior
      cruciate ligament repair by a patellar tendon graft].
AB  - AIM: The aim of this study was to examine radiological and functional outcome
      measurements after anterior cruciate ligament (ACL) reconstruction with a bone
      tendon-bone (BTB) graft. Investigations included assessment of bony integration
      conditions regarding the use of bioabsorbable cross pins or a lateral screw for
      femoral graft fixation. A description of radiological parameters in contrast with
      IKDC findings is also given. METHOD: After ACL injuries, 45 patients underwent an
      ACL repair. For tibial tunnel placement the tibial guide was used in full knee
      extension. A size-specific femoral aimer was placed by using the transtibial
      technique in the "over the top" position and the tunnel was reamed with the acorn
      reamer to 30 mm depth. In 15 patients the BTB graft was fixed with a titanium
      blunt nose screw from the lateral aspect. The cross-pin technique with
      bioabsorbable RIGIDFIX implants was used in 30 patients. All patients underwent a
      follow-up study 36 month postoperatively. Geometric tests of digitised X-rays
      were performed. For clinical and functional outcome studies of ACL repairs the
      IKDC score is widely accepted. The score was modified into numeric parameters for
      15 selected groups of the IKDC score. All 15 categories were rated from 1 to 4
      points (Category A = 4, B = 3, C = 2, D = 1). Clinical and radiological results
      were statistically analysed. RESULTS: According to the literature, tunnel
      placement tibial was physiological in 91% and femoral in 93% of the cases. The
      femoral tunnel was completely invisible in all patients. No necrosis or
      pathological findings in former pin holes were seen. In 24 patients the medial
      compartment space was smaller, but less than 50 % compared to intraoperative X
      rays. Even if the mean of tibial tunnel widening was 2.65 mm it was statistically
      not connected to the results of the IKDC score or X-ray findings of the femoral
      tunnel. Results in the IKDC groups and categories were seen to be in accord with
      overall very good and good outcomes. The modified IKDC score showed a mean of 55
      points with a range from 46 as lowest (1 patient) and 60 in 4 patients (9%) as
      highest numeric score. CONCLUSION: Lateral femoral fixation with screws or
      bioabsorbable cross-pins shows a biological bony incorporation of a BTB graft.
      Tibial tunnel widening was seen but without any functional effects. Overall
      radiological and functional outcomes based on the IKDC score demonstrate results
      in favour of ACL reconstruction with BTB grafts. Due to the narrowing of the
      medial compartment space, more radiological outcome studies with a special
      emphasis on degenerative aspects have to be done.

PMID- 18072038
TI  - [A new possibility for determining the size and position of the tricortical bone
      graft in ventral spine stabilisation].
AB  - AIM: Ventral stabilisation of thoracolumbar fractures is often done with
      autogenous iliac crest grafts as an alternative to other filling and
      stabilisation systems. Today the golden standard for this kind of reconstruction
      is the minimally invasive thoracoscopic stabilization. Often there was a problem
      with the determination of the size and the position of the graft, especially on
      video-assisted minimally invasive stabilisation. The aim of this study was now to
      develop a new instrument that would be able to minimise this kind of
      intraoperative problems. METHOD: For measuring and for checking the exact
      position of the bone graft the vertebrometer as a new measuring apparatus was
      developed. With the simple and good handling of the vertebrometer, there is an
      easy possibility of determine the size and the position of the graft. As this
      tool is made of metal, it is possible to localise and to check the positioning
      and the right size of the necessary bone graft during the intraoperative
      radiological control. DISCUSSION: This tool may help to improve the prognosis of
      osseous integration of the implanted material and lower the rate of
      pseudarthrosis. Furthermore, the handling of the thoracoscopic ventral
      stabilisation may be somewhat easier and, even for the inexperienced surgeon,
      there is now an instrument available to fit in the graft with a satisfactory
      result.

PMID- 18072039
TI  - [Results in the surgical treatment of degenerative lumbar spinal stenosis: a
      retrospective analysis].
AB  - AIM: The intention of this retrospective analysis with follow-up was to assess
      results after decompressive or additional stabilising operations in the clinical
      setting of degenerative lumbar spinal stenosis. METHOD: 74 patients, operated
      upon from 1995 to 2001, were investigated clinically, radiologically and with
      questionnaire score 1 to 8 years (mean 2.5) postoperatively. All data were
      compared and evaluated with the preoperative findings. The results of the group
      with decompressive operations were compared with those for the group with
      additional stabilising operations. RESULTS: The patients with stabilising
      operations showed an improvement of 78.3% on the visual analogue scale and of
      76.1% on the Oswestry score. The patients with decompressive operations showed an
      improvement of 91.7% on the visual analogue scale and of 75.0% on the Oswestry
      score. The difference between the two groups was not significant. There was a
      poorer outcome for previously operated patients or patients with a prolonged
      course of disease. CONCLUSION: The choice of the operative treatment with regard
      to spinal stenosis requires a differentiated preoperative diagnostic procedure in
      accord with the respective living situation and age of the patients. Instability
      in terms of degenerative spondylolisthesis, lumbar scoliosis as well as
      intraoperatively recognised or generated instability has to be additionally
      stabilised with an instrumented fusion in regard to the functional aspect of the
      stenosis.

PMID- 18072040
TI  - [Introduction of a new intervertebral spacer for cervical fusion: results of a
      controlled animal study].
AB  - AIM: This study investigated the fusion properties of a new intervertebral spacer
      that is directly fixed to the adjacent vertebrae by screws. The new spacer was
      compared with an identical spacer without direct fixation but with an additional
      plate and with an autologous bone graft. METHODS: A single-level, cervical fusion
      was performed on 18 mature Merino sheep. Three treatment groups of six sheep each
      were used. Group A used an autogenous bone graft and an additional anterior
      plate. Group B used a titanium solid spacer with a titanium plasma-sprayed (TPS)
      surface and an additional anterior plate. Group C used a similar spacer as group
      B that was directly fixed with the adjacent vertebrae with 4 screws. The standing
      period was 12 weeks. The substrates were evaluated radiographically and
      histologically. RESULTS: Dislocation of the spacer or the bone graft occurred in
      one of the 6 cases in each group A and B, while 5 of the 6 spacers were
      dislocated in group C. Successful fusion was found in 4 of the 6 cases in groups
      A and C and in 5 of the 6 cases in group B. The histomorphometry revealed a
      direct bone apposition at the interface of the bone graft (group A) at 11.6% of
      the surface. The surfaces of the spacers were osseointegrated in 1.1% in group B
      and 1.0% in group C. DISCUSSION: As the dislocation rate shows, the fixation of
      the new spacer (group C) seems to be less stable than the fixation of the bone
      graft or the spacer with the additional plate. Although the intervertebral fusion
      is comparable for all groups, the extent of the osseointegration is much higher
      for the bone graft than for the spacers. In conclusion, the bone graft may offer
      a much better long-term stability than do the spacers.

PMID- 18072041
TI  - [Outcome after cervical anterior fusion--a clinical study of 368 patients].
AB  - AIM: The object of this study was to identify those factors with a direct
      influence on the treatment outcome of anterior cervical fusion. The clinical
      relevance of intervertebral cage subsidence in the course of disease is
      discussed. MATERIAL AND METHODS: In a prospective clinical study we followed up
      368 patients with degenerative disease of the cervical spine one year after
      anterior fusion and cage implantation. RESULTS: We found a statistically
      significant association between a good outcome and young adults with
      monosegmental fusion of the lower cervical spine. CONCLUSIONS: Early treatment of
      moderate degenerative cervical disc diseases using an intervertebral cage and
      anterior fusion leads to a good outcome. Subsidence of the cage does not
      correlate with a poor outcome.

PMID- 18072042
TI  - [Endoprosthesis in the operative treatment of bone tumours of the pelvis].
AB  - AIM: Limb salvage procedures in cases of bone tumours of the pelvis are
      established. In this retrospective study the clinical results after implantation
      of megaprostheses of the pelvis are reported. METHODS: Between November 1994 and
      September 2004 an endoprosthetic replacement of the pelvis was performed in 24
      consecutive patients, fourteen females and ten males. The mean age was 49.3 years
      (range: 17-64 years). In ten cases a complete and in fourteen an incomplete
      internal hemipelvectomy was done. Thirteen patients presented with a primary bone
      tumour and eleven with a bone metastasis. The tumour volume ranged between 50 and
      1315 ml (median: 352 ml). The mean follow-up was 98 months. RESULTS: In 23 of the
      24 patients an R0 resection was achieved. Local recurrences were observed in five
      patients (20.8%). Deep infections developed in ten patients (41.7%)
      postoperatively. In two of these ten patients a secondary external hemipelvectomy
      was necessary. Eight patients (33.3%) developed a paralysis of the femoral and/or
      sciatic nerve, and a loosening of the endoprosthesis was observed in four cases
      (16.7%). Two patients died within 30 days postoperatively (pulmonary embolism,
      dissection of the abdominal aorta). Eight of the 24 patients are still alive, two
      of them after secondary hemipelvectomy and another after removal of the
      endoprosthesis due to infection. The functional results of the five surviving
      patients with an endoprosthesis, according to the MSTS scoring system, are good
      in two and poor in three patients. CONCLUSION: Internal hemipelvectomy and
      reconstruction of the pelvic girdle with endoprostheses is associated with a high
      rate of complications. Each single case should be critically evaluated and
      alternative procedures should be considered.

PMID- 18072043
TI  - [Loosening of a total hip arthroplasty due to metastasis].
AB  - A case report of a metastatic caused loosening of a total hip arthroplasty one
      year after primary implantation is presented. A primary cancer was unknown at
      surgery. Due to suspected low-grade infection, a revision surgery was performed
      and the diagnosis of a metastatically caused loosening could be made. A bronchial
      carcinoma was identified as primary cancer. In spite of the rare incidence of the
      described metastatic loosening, the significance of a differential diagnostic
      strategy and the importance of a histological examination in revision surgery is
      depicted.

PMID- 18072044
TI  - [Gait analysis in limb-preserving tumour surgery--kinematic gait patterns after
      resection of malignant bone tumours near the knee joint].
AB  - AIM: Limb-preserving surgery is the most common therapeutic approach in cases of
      malignant bone tumours near the knee joint. Although good functional results have
      been reported for tumours located in the distal femur, tumours in the proximal
      tibia have been investigated less frequently. The objective of the current study
      was to compare the kinematic gait patterns in patients with tumours in the femur
      vs. the tibia. METHOD: 11 patients with an arthroplasty after a primary malignant
      bone tumour were included (5 femur, 6 tibia). Their speed-specific kinematic gait
      patterns were quantified. 10 healthy volunteers and 6 patients with normal knee
      arthroplasty served as a reference group. RESULTS: The tibia patients walked
      significantly more slowly than the femur patients. They showed a similar overall
      gait pattern predominantly characterised by a hyperextended knee during stance.
      CONCLUSION: The differences in walking speed between the two groups of tumour
      patients did not transfer to different gait patterns. Limb-preserving surgery is
      thus a valuable therapeutic option also for patients with primary tumours in the
      tibia.

PMID- 18072045
TI  - [Faster diagnostics by digital X-ray imaging in the emergency room: a prospective
      study in multiple trauma patients].
AB  - AIM: The object of this study was to provide evidence for a time-reduced
      diagnostic space in multiple trauma patients by use of a digital X-ray system in
      the emergency suite. METHOD: The same algorithm was used in the first attention
      of 66 severely injured patients. For 21 patients from October 2000 to March 2001
      (group 1) conventional X-rays (thorax, pelvis, spine and extremities) were
      performed in the analogue way, for 45 patients from April to December 2001 (group
      2) the new digital system (Philips Optimum and Philips PCR AC 500) was used.
      RESULTS: The two groups were similar concerning age, sex and injury severity. The
      time-space from the patient's delivery in the emergency suite to the handing over
      in the operation theatre or intensive care unit was significantly lower in group
      2 (87 +/- 33 min, p < 0.001) than in group 1 (121 +/- 49 min). CONCLUSION:
      Digital imaging with conventional X-rays in the first attention of multiple
      trauma patients reduces the diagnostic time by more than half an hour, when
      applying the same diagnostic algorithm.

PMID- 18072046
TI  - [An X-ray appliance for postoperative control of osteosynthesis with locking
      plate in patients with distal fracture of the radius].
AB  - PURPOSE: A possible complication in regard to osteosynthetic treatment of a lower
      radius fracture with a locking plate is perforation of the articular surface by
      screws or a malpositioned ulnar fragment. In order to create good conditions for
      a homogeneous, reproducible X-ray picture for post-operative imaging control, an
      appliance for the production of standardised X-ray views has been devised.
      MATERIALS AND METHODS: The X-ray device was constructed at an angle of 20 degrees
      to the camera. The arm was positioned on the appliance in the side beam path, in
      shoulder adduction as well as in the dp-beam in 90 degrees abduction of the
      shoulder. RESULTS: Through standardisation of the X-ray technique the appliance
      it is able to supply comparable and reproducible X-ray images. In practice, the
      representation of both the joint gap and the bolt in the resulting image could be
      improved. CONCLUSIONS: Better and comparable picture series can be created by
      standardisation of the imaging technique using this X-ray device.

PMID- 18072047
TI  - [Bilateral hip dislocation in cerebral palsy children: conservative therapy of
      the less affected hip and adductor tenotomy of the opposite hip].
AB  - AIM: In cerebral palsy children with bilateral hip dislocation, a new therapeutic
      concept was established that treated the less affected hip conservatively and the
      more affected hip simultaneously with an adductor tenotomy. The current study
      assessed whether the clinical and radiological outcome was equal to that of
      established bilateral surgical treatments. We also examined whether this approach
      leads to an adequate motor function improvement of the affected children. METHOD:
      In 41 children with cerebral palsy and bilateral hip dislocation, a prospective
      study assessed the hip abduction, migration percentage (MP) and the motor
      function (Rancho los Amigos scale). Depending on the pretherapeutic status, all
      patients were grouped into 3 abduction and 3 MP groups. The less affected hip was
      treated with a hip abduction splint whereas the more affected hip of the same
      child was simultaneously treated with a subcutaneous adductor tenotomy. All
      patients were assessed annually for 4 years. RESULTS: The hip abduction of the
      conservatively treated hips was pretherapeutically 41.8 +/- 2.6 degrees and
      improved significantly after 1 year. Patients with a pretherapeutic hip abduction
      < or = 20 degrees showed the most improvement. After 4 years, a significant
      deterioration of abduction was avoided in 49%. The pretherapeutic MP of the
      conservatively treated hips was 31.6 +/- 3.4% and was significantly but only
      slightly improved. The 4 year MP was significantly improved and the largest
      improvement was observed when the pretherapeutic MP was larger than 50%. A
      significant MP improvement after 4 years was achieved in 54%. After 4 years, 34%
      had undergone a motor function improvement. In 7% a motor function deterioration
      was observed. Posttherapeutically, the conservatively treated hips showed
      abduction and MP values that were comparable to those of surgically treated hip
      joints. CONCLUSION: In cerebral palsy children with bilateral hip dislocation,
      the conservative treatment of the less affected hip is suitable to achieve
      clinical and radiological results that are equal to the surgical treatment of the
      more affected hip. The concept of a combined conservative and surgical treatment
      of bilateral hip dislocation leads to an adequate motor function improvement that
      is comparable to established bilateral treatments.

PMID- 18072048
TI  - [Promotion of bone healing through clinical application of autologous periosteum
      derived stem cells in a case of atrophic non-union].
AB  - This case report describes the application of periosteum-derived mesenchymal stem
      cells in a patient with atrophic non-union of the distal femur after correction
      osteotomy. While biomechanical treatment devices for various bone defects are
      available in abundance, biological promoters for clinical application in
      situations of critical bone healing are still scarce. We showed radiographically
      that cultivated autologous periosteal bone precursor cells on a three-dimensional
      matrix can promote bone healing in a defect where numerous established methods
      had failed to lead to consolidation. To the best of our knowledge, this is the
      first clinical application of in-vitro cultivated autologous periosteum-derived
      cells for the healing of a large bone defect in humans.

PMID- 18072049
TI  - [Visual circle scale (VCS)--a patient-friendly scale to measure pain compared to
      VAS and Likert scale].
AB  - AIM: The visual analogue scale (VAS) and Likert scale (LS) are widely used but
      the patients might have difficulties to work with these scales and there might be
      errors in calculation. The visual circle scale (VCS) is a graphic construct with
      a simple grading to augment the understanding and ease for calculation. METHOD:
      This study compares the different scales in orthopaedic patients for pain
      assessment postoperatively. In addition, the scales were rated by the patients
      for simplicity, understanding and global rating. RESULTS: Included were 65
      patients (40 women) with an average age of 66 years with 330 pain assessments and
      65 questionnaire ratings. The average pain was LS 42.7, VAS 39.3, VCS 44. The
      correlation coefficients r (Spearman) between all scales were > 0.89 and the same
      held also for sensitivity for change. The VCS was the scale preferred by > 50 %
      of the orthopaedic patients to assess the pain. CONCLUSION: The VCS is able to
      measure pain comparably to the known scales (VAS, Likert scale). From the
      patients point of view it is the preferred scale to work with.

PMID- 18072050
TI  - [Sinus tarsi syndrome].

PMID- 18072051
TI  - Capsule endoscopy: impact on clinical decision making in patients with suspected
      small bowel bleeding.
AB  - BACKGROUND AND STUDY AIM: Capsule endoscopy is widely used for diagnosis of small
      bowel disease; however, the impact of capsule endoscopy on clinical management
      remains uncertain. We conducted a prospective study of the impact capsule
      endoscopy on clinical management decisions in 128 patients with suspected small
      bowel pathology. METHODS: Prior to performing each procedure the
      gastroenterologist predicted the findings of capsule endoscopy and further
      management based on the clinical history and previous investigations. This
      prediction was compared with the actual results of capsule endoscopy and the
      following investigative and therapeutic management. RESULTS: The actual findings
      of capsule endoscopy and the further management were consistent with clinical
      prediction in 93/128 patients (73 %) and, irrespective of capsule endoscopy
      findings, no further procedures were required in 80 % of these patients. In 13
      patients (10 %), gastric or colonic pathology was discovered that had not been
      detected on prior gastroscopy or colonoscopy. Thus, capsule endoscopy findings in
      the small bowel changed clinical management in 22 patients (17 %). In 4 patients,
      positive findings on capsule endoscopy that had not been predicted by the
      examiner prompted referral for abdominal surgery. Conversely, planned surgery was
      canceled in four other patients. CONCLUSION: In this series of patients referred
      for capsule endoscopy, small-bowel findings and appropriate clinical management
      were predicted on clinical grounds alone in approximately three-quarters of
      patients. Repetition of standard upper and lower endoscopy may be useful in many
      patients prior to small-bowel imaging. Referral for capsule endoscopy should take
      into account whether the findings will impact on clinical management; however,
      capsule endoscopy is mandatory in patients in whom surgery for small-bowel
      bleeding is intended.

PMID- 18072052
TI  - Optimal preparation for video capsule endoscopy: a prospective, randomized,
      single-blind study.
AB  - BACKGROUND AND STUDY AIM: Visualization of the small bowel by video capsule
      endoscopy (VCE) is frequently impaired by intestinal contents. Different bowel
      preparations have been studied with controversial results. The aim of this study
      was to determine a satisfactory and tolerable bowel preparation for VCE. METHODS:
      Ninety patients were randomized to three preparation regimens. Group A underwent
      VCE after clear liquid diet and overnight fast, while groups B and C received
      respectively 1 or 2 L of polyethylene glycol (PEG) solution before VCE. For each
      VCE five segments of 10 minutes were selected, one at the start of each quartile
      of the small-intestinal transit time, the fifth being the last 10 minutes of the
      ileum transit. Mucosal visibility was regarded as good if more than 75 % of the
      mucosa could be evaluated. All patients answered a questionnaire regarding
      procedure tolerability. RESULTS: The use of PEG solution led to a significant
      improvement in mucosal visualization. Mucosal visibility was good in the terminal
      ileum in 25 % of patients in group A, 52 % in group B, and 72 % in group C. The
      diagnostic yield did not change significantly. The use of 2 L of PEG solution was
      considered more uncomfortable than no PEG solution or 1 L of the same.
      CONCLUSION: One liter of PEG solution improves mucosal visualization without
      causing discomfort for the patient.

PMID- 18072053
TI  - Diagnosis of small-bowel pathology using paired capsule endoscopy with two
      different devices: a randomized study.
AB  - BACKGROUND AND STUDY AIMS: Capsule endoscopy is an established technique in the
      evaluation of obscure gastrointestinal bleeding. The primary aim of the study is
      to compare the diagnostic yield of the two different capsule endoscopes. PATIENTS
      AND METHODS: Patients with signs of mid-gastrointestinal bleeding after negative
      upper endoscopy and colonoscopy studies were included. Patients were randomized
      to undergo two capsule endoscopies using different capsule endoscopes (Given
      Pillcam SB and Olympus EndoCapsule) in random order. RESULTS: Forty patients (18
      women, 22 men) were included in the study. All EndoCapsules reached the colon
      within the mean recording time of 591 +/- 52 minutes, whereas 33 out of 40
      PillCam SB reached the colon within the mean recording time of 471 +/- 27
      minutes. Lesions were detected in 31 patients: with both devices in 24, only by
      PillCam SB in 2, and, conversely, only by EndoCapsule in 5 (not significant).
      With regard to lesions with high bleeding potential (P2 lesions), PillCam SB
      detected them in 22 patients, EndoCapsule in 25 patients (not significant). In
      all four cases of intestinal P2 lesions that were not detected by the PillCam SB
      but were detected by the EndoCapsule, the PillCam SB had not reached the cecum.
      CONCLUSION: In this study there was a statistically nonsignificant trend for the
      EndoCapsule to detect more bleeding sources in patients with suspected small
      bowel bleeding than did the PillCam SB, which may have been due to the longer
      recording times with the currently available EndoCapsule.

PMID- 18072054
TI  - Can we predict spontaneous capsule passage after retention? A nationwide study to
      evaluate the incidence and clinical outcomes of capsule retention.
AB  - BACKGROUND AND STUDY AIMS: Although capsule endoscopy has become a central
      diagnostic tool for small-bowel evaluation, retention of a capsule remains a
      major concern. This study attempted to investigate the incidence and clinical
      outcomes of capsule retention, and to determine the factors predictive of
      spontaneous capsule passage after retention. PATIENTS AND METHODS: Through a
      nationwide multicenter survey, we retrospectively reviewed the records of 1291
      patients who had a capsule endoscopy between February 2002 and July 2006 in
      Korea. Clinical and procedural characteristics and postprocedural outcomes were
      analyzed for the cases with capsule retention. RESULTS: Capsule retention
      occurred in 2.5 % of total cases (32/1291). The major diseases accompanying
      capsule retention were Crohn's disease, malignant tumors, and tuberculous
      enterocolitis, in decreasing order. In 11 of the 32 patients (34.4 %), early
      surgical or endoscopic interventions were instituted for diagnosis or treatment
      of diseases before retention symptoms developed. The remaining 21 (65.6 %)
      patients initially received medical treatments. Of these, 10 (31.3 %) ultimately
      underwent surgical intervention due to the development of symptoms of intestinal
      obstruction or medical treatment failure. The other 11 (34.4 %) eventually passed
      the capsule. The presence of a larger lumen diameter (greater than two-thirds of
      the capsule diameter) at the stricture site was associated with spontaneous
      passage. CONCLUSIONS: Our large-scale study suggests that retention occurs
      infrequently during capsule endoscopy. Moreover, a retained capsule might
      indicate the best intervention for the offending pathology, or it may
      spontaneously pass in the long run, particularly in patients with less small
      bowel stricture.

PMID- 18072055
TI  - Diagnosis and treatment of obscure gastrointestinal bleeding using combined
      capsule endoscopy and double balloon endoscopy: 1-year follow-up study.
AB  - BACKGROUND AND STUDY AIMS: Several studies have shown the value of capsule
      endoscopy and double balloon endoscopy (DBE) in small-intestinal bleeding. The
      purpose of this study was to evaluate the impact of capsule endoscopy results on
      subsequent DBE examination, and the 1-year clinical outcome of this combined
      approach in patients with obscure gastrointestinal bleeding (OGIB). PATIENTS AND
      METHODS: A total of 45 consecutive patients with OGIB underwent capsule
      endoscopy. Patients with positive capsule endoscopy results underwent DBE for
      biopsy or therapy, and those with negative results underwent further assessment
      for possible diagnostic misses on capsule endoscopy. Tumors, ulcerations, and
      vascular lesions were considered as sources of bleeding. Diagnoses of OGIB
      lesions and clinical outcome were assessed 1 year after these examinations.
      RESULTS: Responsible lesions were found in 22 patients (49 %): 19 lesions in
      18/45 patients (40 %) undergoing capsule endoscopy, and 18/36 patients (50 %)
      undergoing subsequent DBE. In all, 10 tumors, nine vascular lesions, and four
      ulcerations were found. In two patients, vascular lesions were only later
      diagnosed by conventional methods (4 %). Capsule endoscopy results guided our
      choice of the proper DBE model for successful therapeutic intervention in five
      patients. Re-bleeding rates were low during 1-year follow-up of the entire group
      (mean follow-up, 18.8 months): 5 % in cases with positive diagnoses on capsule
      endoscopy and/or DBE, and 12 % in negative cases. CONCLUSIONS: A combined
      approach using capsule endoscopy followed by DBE proves valuable in the diagnosis
      and treatment of patients with OGIB, leaves a low rate of undiagnosed bleeding
      sources, and has a good long-term outcome.

PMID- 18072056
TI  - Characterization of yellow plaques found in the small bowel during double-balloon
      enteroscopy.
AB  - BACKGROUND AND STUDY AIMS: The aim of this study was to characterize yellow (or
      whitish) plaques of the small bowel that were found during double-balloon
      enteroscopy (DBE) performed for small-bowel evaluation. PATIENTS AND METHODS:
      Patients who were being evaluated for small-bowel pathology at our institution
      (for a variety of indications) were included in the study. In 16 patients, DBE
      revealed yellow or whitish submucosal plaques, defined as small, raised,
      submucosal lesions that were well circumscribed and covered by normal-appearing
      small-bowel mucosa. Biopsy tissue obtained during the procedures was stained with
      hematoxylin and eosin and with periodic acid-Schiff stain, and was subjected to
      immunochemical testing using endothelial markers (anti-CD31 and anti-CD34).
      RESULTS: These 16 patients were identified out of a total of 150 DBE procedures
      performed in 120 patients (eight men, eight women; mean age 62, range 33 - 78).
      The lesions were mostly single (range 1 to > 5 lesions), ranging in size from 2
      mm to 15 mm, and were slightly raised (from 1 mm to 2 mm). In four cases the
      plaques could not be biopsied because the patient had a coagulation disorder or
      because the DBE was being performed to investigate severe acute bleeding. In the
      other 12 patients, a characteristic white-yellow liquid exudated from the biopsy
      site in 80 % of lesions, and these 12 patients were shown to have
      lymphangiectasias. No association with an infiltrative disorder could be
      detected. CONCLUSIONS: Yellow and white submucosal plaques are found in up to 13
      % of patients undergoing DBE. They are most likely to be lymphangiectasias and
      are a normal anatomical variant. They do not require further work-up.

PMID- 18072057
TI  - Carbon dioxide insufflation improves intubation depth in double-balloon
      enteroscopy: a randomized, controlled, double-blind trial.
AB  - BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) has been proven
      effective for deep intubation of the small bowel. However, intubation depth is
      limited by distention of the small bowel due to air insufflation during the
      procedure. The present trial investigated whether carbon dioxide (CO (2)) instead
      of standard air insufflation would improve intubation depth during DBE, as well
      as reduce postprocedure pain. PATIENTS AND METHODS: One hundred and twelve
      consecutive patients scheduled for DBE at two centers were randomly assigned to
      either CO (2) or air insufflation during DBE. Patients and endoscopists were
      blinded with regard to the type of gas used. Intubation depth was registered
      using a validated form. Patients scored pain and discomfort during and after the
      examination on a 100-mm visual analog scale. RESULTS: One hundred patients were
      eligible for data analysis (48 in the CO (2) group and 52 in the air group). The
      mean small-bowel intubation depth was extended by 30 % in the CO (2) group
      compared to the air group (230 vs. 177 cm, P = 0.008). The superiority was most
      pronounced for oral DBE, with a 71-cm improvement in intubation depth when using
      CO (2) (295 cm in the CO (2) group vs. 224 cm in the air group, P < 0.001).
      Patient pain and discomfort were significantly reduced in the CO (2) group at 1
      and 3 hours after the examination. CONCLUSIONS: CO (2) insufflation significantly
      extended intubation depth in DBE. CO (2) insufflation also reduces patient
      discomfort. CO (2) insufflation may lead to a higher diagnostic and therapeutic
      yield of DBE, with reduced patient discomfort.

PMID- 18072058
TI  - Double-balloon enteroscopy for endoscopic retrograde cholangiography in patients
      with a Roux-en-Y anastomosis.
AB  - BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) has been proved to be
      effective for deep intubation of the small bowel. Patients with a Roux-en-Y
      enteroanastomosis and biliary problems have been a challenge in gastrointestinal
      practice because of the lack of endoscopic access to the biliary anastomosis. We
      report on the first case series of patients with Roux-en-Y anatomy who have been
      examined using DBE. PATIENTS AND METHODS: Between September 2005 and May 2006, 18
      endoscopic retrograde cholangiography procedures were performed in 13 patients
      (median age 53, range 2 - 81 years) using the DBE technique at our hospital. Most
      of the cases (10/13) had had a liver transplant for primary sclerosing
      cholangitis. The Fujinon T-series DBE system was used in all cases. RESULTS: The
      entero-enteric anastomosis was reached easily in all 18 procedures, and the end
      of the Roux limb was reached in 17/18 procedures. The mean intubation time was 40
      minutes (range 5 - 120 minutes). Adequate imaging was achieved in all but two
      cases, one of whom had a native papilla. Biliary stenting was performed in two
      patients, stent removal in three patients, and removal of a small stone in one
      patient. CONCLUSIONS: Endoscopic access and biliary cannulation in the setting of
      Roux-en-Y anatomy is safe and feasible using the new DBE system for enteral
      intubation. Adaptation of accessories would further improve the utility of the
      procedure.

PMID- 18072059
TI  - A novel model for training in ERCP with double-balloon enteroscopy after
      abdominal surgery.
AB  - BACKGROUND: Since the first presentation of the compactEASIE in 1997, this
      training model has become established for nearly all interventional techniques in
      upper gastrointestinal endoscopy including ERCP. So far, training using double
      balloon enteroscopy (DBE) for ERCP has not become established. AIMS: This paper
      presents a special organ preparation for the compactEASIE model which for the
      first time allows simulation of ERCP in patients who have had prior abdominal
      surgery. Two abdominal organ packages from freshly slaughtered pigs were used to
      create a postsurgical anatomic situation. RESULTS: A life-like training model was
      established for ERCP training in a postsurgical anatomic situation. A Roux-en-Y
      anastomosis was created such that the papilla was located around 100 cm beyond
      the pylorus. The duodenum was closed shortly above the pig papilla at the level
      of the pylorus. The papilla was successfully reached by DBE after 40 minutes. The
      papilla was cannulated and regular contrasting of the biliary system using
      fluoroscopy was achieved. Sphincterotomy, stent placement and exchange, and
      needle-knife sphincterotomy over a 7-Fr stent were conducted successfully.
      CONCLUSION: Modified organ preparations allow the simulation of and training in
      ERCP in postsurgical anatomic situations in training models using animal parts.

PMID- 18072060
TI  - Prospective multicenter quality assessment of endotherapy of biliary stones: does
      center volume matter?
AB  - BACKGROUND AND STUDY AIMS: To study the effectiveness of endoscopic treatment for
      biliary stones in a large case list of patients treated in units with different
      experience and different workloads in a region of northern Italy. PATIENTS AND
      METHODS: We prospectively studied 700 patients undergoing endoscopic retrograde
      cholangiopancreatography or sphincterotomy, in 14 units (> or < 200
      examinations/year), for their first treatment of biliary stones. The difficulty
      of the examinations, the results in terms of clearance of the stones, and the
      late outcomes (24 months) were recorded. A questionnaire (GHAA-9modified) was
      administered 24 hours and 30 days after the procedure to measure patient
      satisfaction. RESULTS: There were six units with a heavy workload and eight with
      a light schedule. There were 176 (25.1 %) difficult examinations (Schutz grades
      3, 4, and 5). Stones were found in 580 (82.9 %) and were cleared in 504 of these
      patients (86.9 %). No differences were observed in the clearance of stones for
      the different groups of difficulty and high- and low-volume centers. Over the 24
      month follow-up period, 96 patients (13.7 %) complained of recurrent symptoms and
      44 (6.3 %) had proof of stones. In all, 603 questionnaires were evaluable and
      more than 80 % of patients expressed satisfaction. CONCLUSIONS: Our findings
      confirm the effectiveness of endoscopic treatment of biliary stones. However, the
      number of patients with symptoms (13.7) after 24 months, with or without
      persistence of stones, was not insignificant. It is feasible to record patient
      satisfaction, and in this series patients stated they were satisfied. Criticism
      mostly concerned pain control and explanations provided before the examination.

PMID- 18072061
TI  - Value of magnifying chromoendoscopy and narrow band imaging (NBI) in classifying
      colorectal polyps: a prospective controlled study.
AB  - BACKGROUND AND STUDY AIMS: Chromoendoscopy in combination with magnifying
      endoscopy is useful in distinguishing neoplastic from non-neoplastic colorectal
      polyps. Narrow band imaging (NBI) has been developed as a new technique to
      differentiate tissue patterns in vivo. The aim of the present study was to
      directly compare the diagnostic values of chromoendoscopy and NBI for the
      differentiation of neoplastic from non-neoplastic colorectal polyps. PATIENTS AND
      METHODS: In total, 200 colorectal polyps from 99 patients were distributed in a 1
      : 1 ratio in order to analyze the surface according to the pit pattern
      classification and vascular patterns by either magnifying chromoendoscopy or NBI
      magnification. Histologic analysis was performed on all lesions. RESULTS: Using
      the Kudo classification of mucosal patterns, NBI with magnification resulted in a
      sensitivity of 90.5 % and a specificity of 89.2 % for the differentiation of
      neoplastic vs. non-neoplastic lesions. This performance was comparable to
      magnifying chromoendoscopy with a sensitivity of 91.7 % and a specificity of 90
      %, respectively. Using vascular patterns for differentiation, NBI with
      magnification correctly identified 93.7 % of neoplastic polyps and 89.2 % of non
      neoplastic colorectal lesions, whereas magnifying chromoendoscopy had a
      specificity of 95 % but a sensitivity of only 66.7 %. CONCLUSION: NBI in
      combination with magnifying endoscopy is a promising tool for the differentiation
      of neoplastic from non-neoplastic colorectal polyps in vivo without the necessity
      of using dye. The detection of capillary vessels with NBI allows the evaluation
      of colorectal lesions based on the vascular patterns with high diagnostic
      accuracy.

PMID- 18072062
TI  - Thoracoscopic enucleation of esophageal leiomyomas: a feasible and safe
      procedure.
AB  - In recent years, minimally invasive approaches have been introduced, providing
      thoracoscopic/laparoscopic techniques in the treatment of esophageal leiomyomas.
      We determined the technical feasibility and patient safety of thoracoscopic
      enucleation of esophageal leiomyomas by evaluation of 10 consecutive patients
      undergoing this procedure. For the surgical approach, a four-trocar access via
      the right pleural cavity in single-lung ventilation was chosen. All minimally
      invasive procedures were successfully completed without conversion to open
      surgery. Every tumor was completely resected without opening of the mucosa. No
      relevant intra- or postoperative complications were detected. These data suggest
      that thoracoscopic enucleation is a feasible and safe procedure for esophageal
      leiomyomas.

PMID- 18072063
TI  - Endoscopic treatment of gastric perforation caused by acute necrotizing
      pancreatitis using over-the-scope clips: a case report.
AB  - Gastric perforation is a rare complication after acute necrotizing pancreatitis.
      We describe endoscopic closure of a gastric perforation that appeared 4 days
      after surgical necrosectomy including splenectomy due to necrotizing
      pancreatitis, using the over-the-scope clip (OTSC) system (Ovesco Endoscopy GmbH,
      Tubingen, Germany). The clips, which are made of nitinol, are loaded onto an
      application cap which is mounted on the distal tip of the endoscope. The lesion
      was closed with two clips and the patient recovered well without reinterventions.
      The lesions showed normal healing on follow-up.

PMID- 18072064
TI  - Endoscopic submucosal dissection using a novel grasping type scissors forceps.
AB  - Endoscopic submucosal dissection (ESD) with a knife is a technically demanding
      procedure that is associated with a high complication rate. The shortcoming of
      this method is the difficulty in fixing the knife to the target lesion. This
      difficulty can lead to unexpected incision, resulting in major complications such
      as perforation and bleeding. To reduce the risk of complications related to ESD,
      we developed a new grasping type scissors forceps (GSF), which can grasp and
      incise the targeted tissue using an electrosurgical current. The ESD procedure
      using the GSF was carried out in an animal model (resected porcine stomachs in
      vitro). After marking the lesion and injecting a solution into the submucosa, the
      lesion was separated from the surrounding normal mucosa following complete
      incision around the lesion using the GSF. A piece of submucosal tissue was
      grasped and cut with the GSF using an electrosurgical current to achieve
      submucosal exfoliation. ESD using the GSF was carried out safely and easily
      without unintentional incision. ESD using GSF appears to be an easy, safe, and
      technically efficient method for resecting gastrointestinal neoplasms.

PMID- 18072066
TI  - Reply to C. Eisenbach et al.

PMID- 18072067
TI  - Safer endoscopic therapy of small-bowel diseases during double-balloon
      enteroscopy.

PMID- 18072069
TI  - Endoscopic injection therapy for post-sphincterotomy bleeding: single injection
      orad to the papilla versus double injection orad to and into the papilla.

PMID- 18072071
TI  - Intensive follow-up may be necessary for endoscopically resected esophageal
      squamous cell carcinoma invading the muscularis mucosae, at least during the
      first year.

PMID- 18072074
TI  - Genetic diversity in Hypericum and AFLP Markers for species-specific
      identification of H. perforatum L.
AB  - One of the top-selling medicinal products worldwide is Hypericum perforatum (St.
      John's Wort). Despite its cosmopolitan distribution and utilization, little is
      known regarding the relationship of the bioactive compounds in H. perforatum to
      the plants from which they are purportedly derived. In this study, amplified
      fragment length polymorphism (AFLP) analysis of 56 Hypericum accessions,
      representing 11 species, was conducted to gain a better understanding of
      diversity within Hypericum species, especially within cultivated accessions of H.
      perforatum, and to establish a molecular methodology that will provide breeders
      and regulators with a simple, affordable, and accurate tool with which to
      identify purported H. perforatum material. Utilizing four primer combinations, a
      total of 298 polymorphic markers were generated, of which 17 were present in all
      H. perforatum accessions and 2 were specific to only H. perforatum. This study
      demonstrates that AFLP can be utilized not only to determine the relationships of
      closely related Hypericum accessions, but as a tool to authenticate material in
      herbal remedies through the use of genetic fingerprinting.

PMID- 18072075
TI  - Relationship between endogenous parathyroid hormone and bone metabolism/geometry
      in female patients treated with glucocorticoid.
AB  - Although the role of PTH (parathyroid hormone) has been debated in glucocorticoid
      (GC)-induced osteoporosis (GIO), clinical data about the relation of endogenous
      PTH to bone metabolism in patients treated with GC are still lacking. The present
      study was performed to examine the relationship of PTH to bone metabolic indices,
      bone mineral density (BMD), and bone geometry in 174 female patients treated with
      oral GC for more than 6 months. Dual-energy X-ray absorptiometry and peripheral
      quantitative computed tomography (pQCT) were employed for the assessment of BMD
      and bone geometry. No elevation of serum PTH levels was observed in patients
      treated with GC. Although serum levels of osteocalcin were not related to serum
      PTH levels, urinary levels of deoxypiridinoline were positively correlated. Serum
      PTH levels were negatively related to BMD at any site. In pQCT, serum PTH levels
      were negatively correlated to both trabecular and cortical volumetric BMD. As for
      bone morphometric indices, serum PTH levels were significantly related to
      endocortical circumferences, cortical thickness, and cortical area. Moreover,
      serum PTH levels were significantly higher in patients with vertebral fractures,
      compared with those without vertebral fractures in GC-treated patients. In the
      present study, serum PTH levels were related to the elevation of bone resorption
      marker, decreased BMD, cortical thinning, and an increase of vertebral fracture
      risk. The elevation of sensitivity to PTH in bone might play some role in the
      pathogenesis of GIO.

PMID- 18072076
TI  - [Distal radius fracture - a goalkeepers' injury in children and adolescents].
AB  - INTRODUCTION: Fractures of the distal radius are the most frequent fractures of
      longbones during childhood and adolescence. A rare mechanism of injury is the
      attempt of a soccer goalkeeper to save the ball, shot with high velocity.
      MATERIAL AND METHODS: Reports of all children and adolescents up to the age of
      14, suffering from a distal radius fracture from a three year period were
      evaluated retrospectively and this particular mechanism of injury was identified.
      All patients were reinvestigated after at least 10 months clinically. RESULTS:
      Amongst 516 distal radius- and distal forearm fractures, there were 213 (41.3 %)
      sports injuries. 61(28.6 %) of them resulted from playing soccer, with 48 (78.7
      %) after a fall. 13 distal radius fractures were identified as a goalkeepers
      injury by a sharply shot ball. We found 6 buckle fractures, 4 complete fractures,
      2 physeal separations Salter II and 1 metaphyseal greenstick fracture. At the
      time of the last follow up investigation all injured had regained their level of
      sports. DISCUSSION: Injuries to the lower extremities are most frequent in
      soccer. The ball itself may lead to fractures and dislocations of the hand and
      finger skeleton, even not unfrequently to distal radius fractures. Wrist
      protectors and an adequate behaviour in game and training may contribute to their
      avoidance.

PMID- 18072077
TI  - [Mountainbike injuries in world-cup and recreational athletes].
AB  - This study investigated the incidence and frequency of injuries in mountainbike
      sports among competitive and recreational athletes. In a retrospective study
      design mountain-bike athletes were interviewed by means of a standardized
      questionnaire with regard to sports injuries and damages within the previous two
      years. The evaluation of time relative injury-rate was carried out under
      consideration of class and competition discipline. 75 % of the distributed
      questionnaires returned completed by 106 World-Cup (39 female symbol 67 male
      symbol, 23.1 y) and 134 recreational athletes (17 female symbol 117 male symbol,
      27.4 y). Approximately 80 % of the World-Cup and about 50 % of the recreational
      athletes reported about at least one severe injury. World-Cup downhill athletes
      (1.08 injuries/ 1000 h) show a more than doubled time-related injury-rate in
      comparison with Cross-Country athletes (0.39 injuries/ 1000 h). Injuries of the
      lower (47 vs. 35 %) and upper extremity (40 vs. 41 %) show comparable prevalence
      for competitive and recreational cyclists. In the group of recreational athletes
      open wounds dominate, competitive athletes demonstrate a significant higher
      fracture-rate (p < 0.01). Within the World-Cup athletes head injuries stand out
      (n = 40). Although World-Cup participation does not result in essential injury
      increase, the downhill discipline is characterized by a higher injury risk.
      Presumably in view of the performance orientation, there is a higher degree of
      risk readiness. Despite the riding performance and the obligatory safety
      equipment a remarkable number of bone and head injuries results.

PMID- 18072078
TI  - [Ruptures of the pectoralis major muscle - clinical results after operative and
      non-operative treatment].
AB  - AIM: Ruptures of the pectoralis major muscle should be treated operatively due to
      the expected loss of strength following conservative treatment. Minimal-invasive
      surgery technique using suture anchors can lead to perfect anatomical refixation
      of the muscle. We report mid-term clinical results. METHODS: We present clinical
      results of a comparative study concerning ruptures of the pectoralis major
      muscle. Between 2001 and 2006 a total number of 9 patients were treated
      operatively using suture anchors. The surgical procedure is described. A control
      group (n = 4) consisted of patients being treated conservatively in 1999 und
      2000. For evaluation of results Bak's score was used. RESULTS: The mean follow-up
      time was six months. We found 4 very good and 4 good results, only one patient
      showed a satisfying result. Among the patients who had followed the conservative
      treatment regime only one had a good outcome while three patients remained in a
      satisfying condition. All type-1-ruptures according to Roller showed
      postoperatively nearly equal strength conditions for both sides. CONCLUSION: The
      operative treatment of acute ruptures of the pectoralis major muscle in active
      people and athletes leads to better results concerning restoration of strength
      than conservative or delayed treatment. The surgical technique depends upon the
      type of rupture which has to be determined intraoperatively. The use of suture
      anchors aiming for intraosseous fixation helps to avoid intraoperative
      complications and leads to stable conditions with nearly full restoration of
      strength.

PMID- 18072079
TI  - [Proximal adductor longus tendon tear in high level athletes. A report of three
      cases].
AB  - Chronic groin pain in athletes frequently results from adductor insertional
      tendinopathy. Adductor tenotomy has been proposed for cases recalcitrant to
      conservative treatment. However, acute tears of the proximal adductor tendons
      have rarely been described and all of them underwent early repair. This report
      reviews the relevant literature and adds three more acute proximal adductor
      longus insertional tears. Diagnosis has been made clinically and was confirmed by
      ultrasound and MRI. Following early repair using suture anchors and functional
      postoperative rehabilitation, full sports ability was re-established five, six
      and seven months, respectively.

PMID- 18072080
TI  - [A case of a tumorsimulating expansion caused by anabolic androgen steroids in
      body building].
AB  - Despite intensive information on possible side effects and complications of
      performance-enhancing substances in sports, the use of AAS (anabolic androgen
      steroids) is far common. Particularly in sports like bodybuilding or weight
      lifting AAS are used for setting up muscle mass and increasing muscle power. We
      present the case of a 27 year old bodybuilder, who was transferred due to
      suspected malignant expansion of the upper limb to a department of orthopaedic
      surgery, not knowing that the patient had injected AAS. At biopsy the tumor was
      found to be an abscess formation, that had to be treated surgically with
      curettage. The microbiological analysis detected an infection with Pseudomonas
      fluorescens and Erwinia species. Erwinia species are associated with plants,
      Pseudomonas fluorescens is found in feces, sewage and soil. It is obvious, that
      the infection is caused by an inappropriate injection of AAS or by the
      contamination of the injected substances.

PMID- 18072081
TI  - [Isolated depressed fracture of the cheek bone in alpine rapid-river canoeing].
AB  - Whitewater kayaking is a rapidly growing form of extreme sport with a high risk
      potential for upper-body injuries, mainly concerning the head and torso. Direct
      impact traumata, such as a creek bone fracture, require an operation. The follow
      up treatment is aimed to prevent any loading from taking place. If necessary, a
      special facemask can be made to avoid injuries resulting from direct contact with
      hard surfaces. A suitable helmet for kayaking should include facial protection,
      which is not very common.

PMID- 18072082
TI  - Glial cell line-derived neurotrophic factor expression in the brain of adult
      zebrafish (Danio rerio).
AB  - In mammals, glial cell line-derived neurotrophic factor (GDNF) is a growth factor
      of many neuronal populations in the central, peripheral and autonomous nervous
      system. GDNF may also function as a morphogen during kidney development and may
      regulate spermatogonial differentiation. GDNF has been characterised in zebrafish
      embryos and was demonstrated experimentally to be critical for the development of
      the enteric nervous system. However, in adult zebrafish, no data exist regarding
      GDNF expression and localisation in the brain and in different organs. Thus, the
      aim of the present study was to investigate the expression of GDNF in the brain
      of adult zebrafish (Danio rerio). Transcripts of GDNF mRNA were observed in brain
      extracts by a standard RT-PCR. The presence of the protein in the brain
      homogenates was confirmed by SDS-PAGE electrophoresis and Western blotting
      analysis. Immunohistochemistry and in situ hybridization experiments showed that
      GDNF protein and mRNA were localised in various nuclei of the telencephalon,
      diencephalon, mesencephalon, cerebellum and medulla oblongata of the zebrafish
      brain. In conclusion, this study showed that the expression of GDNF was not
      restricted to developmental periods but it seems that this factor might be
      involved in adult zebrafish brain physiology, as observed in mammals.

PMID- 18072083
TI  - Abnormal collagen deposition in synovia after collagen type V immunization in
      rabbits.
AB  - Sinovitis in Scleroderma (SSc) is rare, usually aggressive and fully resembles
      rheumatoid arthritis. Experimental models of SSc have been used in an attempt to
      understand its pathogenesis. Previous studies done in our laboratory had already
      revealed the presence of a synovial remodeling process in rabbits immunized with
      collagen V. To validate the importance of collagen type V and to explore the
      quantitative relationship between this factor and synovia remodeling as well as
      the relationship between collagen type V and other collagens, we studied the
      synovial tissue in immunized rabbits. Rabbits (N=10) were immunized with collagen
      V plus Freund's adjuvant and compared with animals inoculated with adjuvant only
      (N=10). Synovial tissues were submitted to histological analysis,
      immunolocalization to collagen I, III and V and biochemical analysis by
      eletrophoresis, immunoblot and densitometric method. The synovial tissue
      presented an intense remodeling process with deposits of collagen types I, III
      and V after 75 and 120 days of immunization, mainly distributed around the
      vessels and interstitium of synovial extracellular matrix. Densitometric analysis
      confirmed the increased synthesis of collagen I, III and V chains (407.69+/
      80.31; 24.46+/-2.58; 70.51+/-7.66, respectively) in immunized rabbits when
      compared with animals from control group (164.91+/-15.67; 12.89+/-1.05; 32+/
      3.57) (p<0.0001). We conclude that synovial remodeling observed in the
      experimental model can reflect the articular compromise present in patients with
      scleroderma. Certainly, this experimental model induced by collagen V
      immunization will bring new insights in to pathogenic mechanisms and allow the
      testing of new therapeutic strategies to ameliorate the prognosis for scleroderma
      patients.

PMID- 18072084
TI  - Differential expressions and roles of hypoxia-inducible factor-1alpha, -2alpha
      and -3alpha in the rat carotid body during chronic and intermittent hypoxia.
AB  - The HIF-1alpha expression in the carotid body (CB) is central to the
      transcriptional regulation of the CB structural and functional changes in chronic
      hypoxia (CH). The CB plays pathogenic roles in cardiovascular morbidity in
      patients with sleep-disordered breathing; yet, the expression and role of HIF
      alpha subtypes in intermittent hypoxia (IH), resembling recurrent episodic apnea,
      are unclear. We hypothesized a divergent role of HIF-alpha subtypes, regulated by
      differential expression in the CB response to IH. A time-course analysis of the
      CB volume, and expression profiles of the HIF-1alpha, -2alpha, -3alpha and HIF
      regulated gene products, including vascular endothelial growth factor (VEGF),
      endothelin-1 (ET-1), and tyrosine hydroxylase (TH), showed a significant
      difference in the lack of increase in the rat CB volume, HIF-1alpha and VEGF
      expression during IH, despite an increase in the mRNA level of HIF-1alpha and the
      prominent increase of volume and expression in the CH group. In contrast, there
      were increased CB expressions of HIF-2alpha and -3alpha, and also ET-1 and TH in
      both IH and CH groups. Results demonstrated a significant role played by HIF
      2alpha and -3alpha in the CB response to IH, which could be complementary to the
      expression and role of HIF-1alpha under hypoxic conditions. This differential
      regulation of the HIF-alpha subtypes and pathways could account for the
      morphological and neurochemical discrepancy in the CB responses to IH and CH.

PMID- 18072085
TI  - Epithelial cell renewal in the digestive gland and stomach of mussels: season,
      age and tidal regime related variations.
AB  - The natural variability in cell proliferation activity in the epithelium of the
      digestive gland and stomach was investigated in mussels, Mytilus
      galloprovincialis (Lmk), of different age and tidal level at different seasons.
      After treating mussels with the thymidine analogue bromodeoxyuridine (BrdU) for 6
      hours, BrdU immunohistochemistry was performed every 2 hours for the next 36. The
      relative proportion of BrdU positive cells was quantified as BrdU labelling (per
      thousand). Marked seasonal differences were recorded in BrdU labelling, with much
      higher proliferating activity in summer than in autumn and winter. Cell
      proliferation seemed not to be significantly dissimilar between mussels of
      different age (size). In contrast, the digestive gland epithelium of mussels from
      intertidal and subtidal populations differed not only in the levels but also in
      the pattern of variation of BrdU labelling, which in intertidal mussels appeared
      to be modulated by photoperiod and tide, unlike in subtidal mussels, in which
      variations followed a circatidal pattern.

PMID- 18072087
TI  - Ultrastructural study of human glomerular capillary loops with IgA nephropathy
      using quick-freezing and deep-etching method.
AB  - Immunoglobulin A (IgA) nephropathy shows great variability regarding the
      histological features of the lesions of human renal glomeruli. In the present
      study, the quick-freezing and deep-etching (QF-DE) method was used to analyze the
      glomerular ultrastructure of biopsied kidney tissues from children with IgA
      nephropathy. Biopsied renal tissues were routinely prepared for light microscopy,
      immunofluorescence microscopy, conventional electron microscopy, and replica
      electron microscopy. The three-dimensional ultrastructure of glomeruli of the
      kidney was clearly observed by using the QF-DE method. Three layers of glomerular
      basement membranes, i.e., middle, inner and outer layers, were clearly detected
      in the replica electron micrographs. The middle layer was 343.0+/-24.2 nm (n=20)
      in width and formed polygonal meshwork structures. We also observed slit
      diaphragms, electron-dense mesangial deposits, and increased amounts of mesangial
      matrix and foot process effacement. Many delicate filaments were found to be
      distributed from the apical to the bottom portions between neighboring foot
      processes. The ultrastructural difference between the replica electron
      micrographs and conventional electron micrographs was found to be especially
      marked in the appearance of foot processes and connecting filaments between the
      neighboring foot processes. The examination of extracellular matrix changes, as
      revealed at high resolution by the QF-DE method, gave us some morphofunctional
      information relevant to the mechanism of proteinuria with IgA nephropathy.

PMID- 18072086
TI  - Melanocyte localization and distribution in human cholesteatoma.
AB  - INTRODUCTION: Melanocytes in skin are derived from the neural crest and colonize
      the epidermis in the first trimester of gestation. Melanocytes have been observed
      in the nasopharyngeal, inner ear and oral mucosa and should therefore be present
      in the middle ear mucosa. AIMS: To identify and determine the distribution of
      melanocytes in human cholesteatoma and normal meatal skin in Caucasian adults.
      MATERIAL AND METHODS: Human cholesteatoma (n=18) and normal meatal skin samples
      (n=10) were investigated immunohistochemically with anti-HMB-45 and MART-1
      antibodies. Localization and distribution of melanocytes were assessed in the
      epidermis and cholesteatoma using an automatic analyzing system. RESULTS: Regular
      skin exhibited melanocytes within the epidermis and accounted for 10% of the
      total cell number. They occurred partly as membrane-bound clusters. Cholesteatoma
      matrix melanocytes were observed in the basal layer and exhibited an oval or
      roundmorphology. Decreased numbers of melanocytes in the basal layer correlated
      with keratinization within cholesteatoma samples. Melanocytes revealed
      monomorphous nuclei, abundant cytoplasm containing particles of melanin. Found
      adjacent to glands and blood vessels, melanocytes were also scattered among the
      mesenchymal cells. Accounting for 2-6% of the total cell number within the
      squamous epithelium, melanocyte density was significantly lower in cholesteatoma
      tissue than in skin. CONCLUSIONS: The melanocyte distribution pattern was
      different when comparing the epithelia of skin and cholesteatoma. The presence of
      melanocytes in cholesteatoma may be due to an ingrowth, consequently controlled
      by keratinocyte-derived signals. In terms of the pathogenesis of cholesteatoma,
      neither squamous metaplasia nor melanocyte metaplasia can be excluded by our
      data.

PMID- 18072088
TI  - Expression of activity-dependent neuroprotective protein in the brain of adult
      rats.
AB  - Activity-dependent neuroprotective protein (ADNP) is a VIP-regulated gene, which
      is essential for brain development. A synthetic peptide (NAP) derived from the
      ADNP sequence is highly neuroprotective, therefore it has been hypothesised that
      ADNP has a similar role. ADNP contains classical transcription factor motifs and
      nuclear localisation domains, but it has also been reported to be secreted and to
      co-localise with microtubules, indicating that ADNP may have multiple functions.
      We investigated the pattern of ADNP expression by immunohistology in normal rat
      brain, in order to generate a framework for future studies examining changes in
      ADNP expression in response to noxious stimuli or in models of disease. We found
      widespread ADNP-like immunoreactivity in neurons throughout the rat brain, with
      the highest expression in the cerebellum, and strong expression in the thalamus,
      mesencephalon, pons and medulla oblongata. ADNP-like immunoreactivity was mainly
      observed in the cytoplasm of neurons, and fibre tracts were often strongly
      positive as well. In addition, positive neuronal nuclei were occasionally
      observed. ADNP-like immunoreactivity was lost in degenerating "dark" neurons,
      whereas it appeared to locate to the nucleus in some of the morphologically
      unaltered adjacent cells. Occasional astrocyte and microglial cells were also
      positive. We suggest that the widespread expression of ADNP may correlate with
      the wide-ranging protective effects of NAP, and that the cytoplasmic and axonal
      localisation of ADNP-like immunoreactivity suggests additional, non
      transcriptional functions of ADNP.

PMID- 18072089
TI  - Fluoro-edenite fibres induce lung cell apoptosis: an in vivo study.
AB  - We previously showed that apoptosis in the lungs of sheep exposed to fluoro
      edenite fibres is induced via the receptor pathway. The present study was
      performed to gain further insights into the mechanisms of activation of
      programmed cell death induced by the fibres. Fluoro-edenite fibres are similar in
      size and morphology to some amphibolic asbestos fibres. They have been found in
      benmoreitic lavas, in the local stone quarry, in building materials and in road
      paving at Biancavilla, a town in eastern Sicily (Italy), where epidemiological
      surveys revealed a cluster of mortality from pleural mesothelioma. Inhalation of
      asbestos fibres can cause chronic inflammation and carcinogenesis. Since fluoro
      edenite has been shown to activate the apoptotic process, we set out to
      characterise the expression of apoptosis-regulating proteins in fluoro-edenite
      exposed lung disease and sought to determine if apoptosis results from fluoro
      edenite exposure. Lung tissue from apparently healthy sheep habitually grazing
      near Biancavilla was processed for immunohistochemical localisation of bcl-2 and
      bax. Results showed epithelial and interstitial bax overexpression, especially in
      cells directly in contact with the fibres, and negative bcl-2 immunoexpression.
      TUNEL-positive cells were detected in alveoli and connective tissue. The
      integrity of alveolar epithelium and alveolar apoptosis are critical determinants
      in the pathways that initiate fibrogenesis in the lung and fibroblastic foci are
      usually found close to abnormal or denuded alveolar epithelium. Our results are
      consistent with the hypothesis that apoptosis is an important mechanism for
      removing cells with irreparable fluoro-edenite-induced genetic changes that
      predispose them to a neoplastic evolution.

PMID- 18072090
TI  - Nuclear localization of TRK-A in liver cells.
AB  - The liver represents a site of expression of neurotrophins and their receptors.
      We have characterized the expression and intracellular localization of the nerve
      growth factor (NGF) receptor, Trk-A, in liver cells in vivo and in vitro. In both
      normal and fibrotic liver tissue, Trk-A immunostaining was present in different
      cell types, including parenchymal cells and cells of the inflammatory infiltrate.
      In hepatocytes and activated stellate cells (HSC), Trk-A showed a predominant
      nuclear localization, both in the presence and absence of injury. In cultured
      HSC, Trk-A was found to be functional, because exposure of the cells to
      recombinant NGF resulted in stimulation of cell migration and activation of
      intracellular signaling pathways, including Ras-ERK and PI3K/Akt. Remarkably, in
      cultured HSC, Trk-A staining was found constitutively in the nucleus. In these
      cells, Trk-A could be stained only by antibodies directed against the
      intracellular domain but not by those recognizing the extracellular portion of
      Trk-A suggesting that the intracellular portion of the receptor is the major
      determinant of nuclear Trk-A staining. In contrast to HSC, freshly isolated
      hepatocytes did not show any nuclear localization of the intracellular portion of
      Trk-A. In pheocromocytoma cells, nuclear staining for Trk-A was not present in
      conditions of serum deprivation, but could be induced by exposure to NGF or to a
      mixture of soluble mediators. We conclude that nuclear localization of the
      intracellular domain of Trk-A is observed constitutively in liver cells such as
      HSC, while in other cell types it could be induced in response to soluble
      factors.

PMID- 18072091
TI  - Characterization of glycoconjugates in the secretory epithelium of the equine
      ampulla ductus deferentis.
AB  - The present work was undertaken to determine the glycoconjugates secreted by the
      epithelium of the equine ampulla ductus deferentis, using conventional (PAS, AB
      pH 2.5, AB pH 1.0) and lectin histochemical procedures in conjunction with
      enzymatic digestion and chemical treatment. The presence of abundant apical
      cytoplasmic blebs suggests that the equine ampulla secretes its products mainly
      in an apocrine manner. Glandular cells secrete neutral and acidic sialylated
      glycoconjugates as revealed by conventional histochemical procedures. Lectin
      histochemistry helped us to discover the following histological positive sites:
      the mucosal cells, the glandular epithelial cells, the apical cytoplasmic blebs
      and the basal cells. The ampullary secretions contained both glycoproteic
      material (revealed by Con-A-, LCA-, GSA-II-, WGA-, RCA-I- positivity) and
      sialomucins (evidenced by the reactivity of GSA-II, SBA, PNA and RCA-I after
      sialidase digestion) having different functional roles. The mucosal cells reacted
      with Con-A, LCA, and also with sialidase/GSA-II-, SBA-, PNA-, and RCA-I
      sequences, contributing to the chemical heterogeneity of ampullary secretions.
      DBA lectin was a specific marker for basal cells. The results obtained were
      compared with our previous findings regarding the differences in the lectin
      binding pattern of the plasma-membrane of equine sperm collected from epididymal
      cauda and the ampulla ductis deferentis. Our results support other studies that
      indicate that ampullary secretions are involved in altering the plasma-membrane
      glycoconjugates of spermatozoa, contributing to their maturation.

PMID- 18072092
TI  - Peripheral chemoreceptors: postnatal development and cytochemical findings in
      Sudden Infant Death Syndrome.
AB  - The aim of the present study is to give a review of the postnatal development of
      peripheral chemoreceptors - carotid body, paraganglia, and pulmonary
      neuroendocrine cells (PNEC) - with implications in Sudden Infant Death Syndrome
      (SIDS). In the postnatal period, the hypoxic chemosensitivity of the carotid body
      gradually develops. Changes include proliferation of type I and II cells,
      increased numbers of dense core vesicles and K+ channels, and modifications of
      neurotransmitter/neuromodulator and receptor expression. Chromaffin paraganglia
      show increased expression of nitric oxide synthase and neuropeptides, and
      increased innervation. Innervation of PNEC develops fully only in the first
      postnatal period, after which their density falls. The neuropeptides produced by
      PNEC also changes, with increased expression of calcitonin gene-related peptide
      and neuropeptide YY and reduced expression of calcitonin and gastrin-releasing
      peptide. Most of the findings in the carotid body of SIDS victims, i.e., decrease
      in type I cells and dense cytoplasmic granules, and increase in progenitor cells,
      indicates immaturity of the carotid body, which may play a role in SIDS in the
      form of underlying biologic vulnerability. Aorticopulmonary paraganglia
      hyperplasia and increase of PNEC are also found in SIDS, and may be epiphenomena
      of alterations of the respiratory function with a pathogenetical role in SIDS. A
      comprehensive view of the pathogenesis of SIDS should also arise from the
      integration of peripheral chemoreceptors findings with neuro- and
      cardiopathologic ones.

PMID- 18072093
TI  - Apoptosis of the cerebellar neurons.
AB  - Naturally occurring neuronal death (NOND) is an essential phenomenon during the
      course of normal development of the nervous system. Studies in vivo and on
      organotypic cultures have helped to elucidate the basic histological and
      ultrastructural features, as well as the main cellular mechanisms of NOND in
      several areas of the brain. This review examines the existing evidence about the
      two waves of apoptotic cell death that affect the different types of cerebellar
      neurons in normal development and certain pathological conditions. The first wave
      regards neuronal progenitors and pre-migratory neuroblasts, the second post
      migratory neuroblasts and mature neurons. The underlying cellular and molecular
      mechanisms are discussed critically also in the light of their relevance to
      neurodegenerative diseases.

PMID- 18072094
TI  - Atherosclerosis and oxidative stress.
AB  - This review focuses on the morphological features of atherosclerosis and the
      involvement of oxidative stress in the initiation and progression of this
      disease. There is now consensus that atherosclerosis represents a state of
      heightened oxidative stress characterized by lipid and protein in the vascular
      wall. Reactive oxygen species (ROS) are key mediators of signaling pathways that
      underlie vascular inflammation in atherogenesis, starting from the initiation of
      fatty streak development, through lesion progression, to ultimate plaque rupture.
      Plaque rupture and thrombosis result in the acute clinical complications of
      myocardial infarction and stroke. Many data support the notion that ROS released
      from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, myeloperoxidase
      (MPO), xanthine oxidase (XO), lipoxygenase (LO), nitric oxide synthase (NOS) and
      enhanced ROS production from dysfunctional mitochondrial respiratory chain,
      indeed, have a causatory role in atherosclerosis and other vascular diseases.
      Moreover, oxidative modifications in the arterial wall can contribute to the
      arteriosclerosis when the balance between oxidants and antioxidants shifts in
      favour of the former. Therefore, it is important to consider sources of oxidants
      in the context of available antioxidants such as superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GPx), glutathione reductase and
      transferases thiol-disulfide oxidoreductases and peroxiredoxins. Here, we review
      also the mechanisms in which they are involved in order to accelerate the pace of
      the discovery and facilitate development of novel therapeutic approaches.

PMID- 18072095
TI  - Back to the future: introducing the journal of medical toxicology.

PMID- 18072096
TI  - Vasopressin treatment of verapamil toxicity in the porcine model.
AB  - INTRODUCTION: Vasopressin is a novel vasopressor agent used for intractable
      hypotension. There is little published data available on its use in the poisoned
      patient. We performed a randomized, controlled, blinded trial in a porcine model
      to study the effects of vasopressin infusion on mean arterial pressure after
      verapamil poisoning. METHODS: Eighteen anesthetized monitored swine received a
      verapamil infusion of 1 mg/kg/hr until the mean arterial pressure (MAP) had
      decreased to 70% of baseline. At this time, a continuous infusion of either
      vasopressin (0.01 U/kg/min) or an equal volume of normal saline was initiated.
      The swine were monitored for 60 minutes after initiation of the study infusion.
      The primary outcome was MAP. RESULTS: There was no statistically significant
      difference between the two groups in MAP, cardiac output or systemic vascular
      resistance. One half (four of eight) of the animals in the vasopressin group
      died, compared with 20% (two of ten) of those in the saline group. CONCLUSIONS:
      Vasopressin infusion decreased the survival of verapamil-poisoned swine when
      compared to those treated with saline alone in this experimental model.

PMID- 18072098
TI  - Use of neostigmine for the management of drug induced ileus in severe poisonings.
AB  - INTRODUCTION: Effective whole bowel irrigation may be difficult in the presence
      of drug-induced ileus. Neostigmine, which inhibits the enzymatic degradation of
      acetylcholine, has been suggested to improve drug-induced ileus. We present two
      poisoning cases in which neostigmine was used to facilitate gut decontamination
      complicated by ileus. CASE REPORTS: A 47-year-old woman, after overdose with
      sodium valproate, venlafaxine, and ibuprofen, developed ileus that prevented
      whole bowel irrigation. Neostigmine, 2.5 mg intravenously followed by 1.25 mg
      three hours later, led to improved bowel transit and successful whole bowel
      irrigation. A 25-year-old man developed ileus after overdose with venlafaxine,
      dothiepin, and ethanol. Neostigmine administration led to improved intestinal
      motility and successful whole bowel irrigation. DISCUSSION: We demonstrate
      facilitated gut decontamination temporally associated with administration of
      neostigmine in two patients judged to have drug-induced ileus following overdose.
      No significant adverse events related to neostigmine were observed.

PMID- 18072097
TI  - The effect of amiodarone pretreatment on survival of mice with cocaine toxicity.
AB  - INTRODUCTION: Cocaine is a common drug of abuse and use has been associated with
      ventricular dysrhythmias. Published guidelines suggest that amiodarone is the
      first line antidysrhythmic for ventricular tachycardia and fibrillation. However,
      the effects amiodarone in the setting of cocaine toxicity are unknown and
      unstudied. The purpose of this study was to evaluate the safety and efficacy of
      amiodarone pretreatment in a murine model of acute cocaine toxicity. METHODS:
      This was a randomized, blinded, placebo controlled investigation using male CF-1
      mice weighing 29-37 g. First, the safety of an intraperitoneal dose of amiodarone
      (40 mg/kg) was confirmed in 5 mice. Second, based on preliminary investigations,
      an approximate intraperitoneal LD50 dose of cocaine (110 mg/kg) was identified
      and used as the cocaine dose in this study. Animals were then randomized to 2
      groups. The control group received 0.5 mL of intraperitoneal 0.9% saline 30
      minutes before cocaine. The study group received 40 mg/kg of intraperitoneal
      amiodarone (40 mg/kg) 30 minutes before cocaine. A blinded observer monitored
      mice for 2 hours after cocaine administration. RESULTS: No mice in the amiodarone
      only group developed any signs of toxicity or died. In the saline + cocaine group
      31/32 (96.9%; 95% CI 83.8 to 99.9) mice seized with a median time to seizure of
      2.5 minutes, and 23/32 (71.9%; 95% CI 52.3 to 86.3) died with a median time to
      death of 5.5 minutes. In the amiodarone + cocaine group 31/33 (93.9%; 95% CI 79.0
      to 99.3) mice seized with a median time to seizure of 2.0 minutes, and 24/33
      (72.7%; 95% CI 54.5 to 86.7) died with a median time to death of 6.0 minutes. All
      animals that died did so within 9 minutes. The difference in the proportion of
      animals dying in the amiodarone + cocaine group compared to the saline + cocaine
      group was 0.008 (-21 to 22%). CONCLUSIONS: In this study, pretreatment with
      amiodarone in cocaine poisoned mice resulted in no change in seizure incidenceor
      mortality. However, definite conclusions about the reason for these findings
      cannot be drawn from this model.

PMID- 18072099
TI  - Foxy methoxy: a new drug of abuse.
AB  - INTRODUCTION: In 1999, a new synthetic tryptamine, 5-MeO-DIPT, became known as a
      street drug, with the street name of "Foxy" or "Foxy Methoxy". By February 2003,
      the DEA reported law enforcement seizures and/or reports of abuse in 12 states.
      We report a case along with an analysis of poison center data on this new drug of
      abuse. CASE REPORT: A 19-year-old male was brought to the emergency department
      following ingestion of a larger than his usual dose of Foxy. Upon arrival, he had
      hallucinations, hypertension, tachycardia, mydriasis, and catalepsy. Symptoms
      resolved within two hours after administration of lorazepam and he recovered
      uneventfully. DISCUSSION: The AAPCC TESS database contained 41 exposures to
      "Foxy" between April, 2002 and June, 2003; 26 had moderate or major effects,
      indicating this drug has significant toxic potential. Given the expanding use of
      this and other club drugs, the spectrum of toxicity from this new agent will
      continue to be elucidated.

PMID- 18072101
TI  - Issues in the management of dietary supplement use among hospitalized patients.
AB  - Herbs and dietary supplements (HDS) are in widespread use in the United States,
      and are especially prevalent among chronically ill patients. This population is
      more likely to be admitted to health care facilities where they may continue to
      use HDS. The risk of adverse effects from HDS used during admission places
      significant liability on clinicians and hospitals. We describe the response of
      health care facilities in the Boston, Massachusetts area to this problem, and
      propose elements of a hospital policy which increases patient safety and
      satisfaction and minimizes the likelihood for adverse effects from HDS.

PMID- 18072100
TI  - Unusual presentation of iatrogenic phenytoin toxicity in a newborn.
AB  - BACKGROUND: Medication errors may produce severe toxicity resulting in
      hospitalization. This can be compounded if the physician obtains the wrong
      concentration from a reference manual and a pharmacy miscalculates the
      conversion. We report a child presenting with ileus, hypothermia and lethargy
      after receiving supratherapeutic dosing of phenytoin after a concentration
      miscalculation. CASE REPORT: A one-month-old infant presented to the Emergency
      Department with progressive worsening of abdominal distension, diminished
      activity, and a one day history of difficulty feeding secondary to a decreased
      level of consciousness. The past medical history was significant for neonatal
      Group B Strep meningitis with seizures. Among the child's discharge medications
      was a prescription for phenytoin (30 mg/5 mL) 2.5 cc by mouth three times daily.
      On exam, the child was hypothermic with pink mottled skin, poor responsiveness,
      prolonged capillary refill, abdominal distension with hypoactive bowel sounds,
      and a dysconjugate gaze. The Initial phenytoin serum concentration was 91.8
      mcg/mL. She was admitted to the PICU and was started on ampicillin and cefotaxime
      for R/O sepsis. Phenytoin was withheld and subsequent serum concentrations
      revealed an extremely slow elimination (mcg/mL vs. time pair coordinates were
      78.2/13.3h; 74.3/62.3h; 43.7/109.6h; 10.8/160.9h) reflecting zero-order kinetics.
      Post discontinuing antibiotics, phenytoin levels decreased at rates expected. She
      was discharged after resolution of symptoms. The MD who had written the phenytoin
      prescription had based it on the Harriet Lane Handbook, 2000 Ed. The 30 mg/5 mL
      formulation has been unavailable in the US for several years. A community
      pharmacy substituted the 125 mg/5 mL formulation, but miscalculated the dosage to
      be 1.6 cc (40 mg) tid. CONCLUSIONS: Abdominal distension and ileus may be
      presenting symptoms in children at toxic phenytoin levels. Ampicillin and
      cefotaxime may effect the elimination rate of phenytoin at such levels. We report
      one of the highest phenytoin levels recorded after therapeutic misadventure.
      Physicians must be aware of inaccuracies in reference manuals that may result in
      dosing errors.

PMID- 18072102
TI  - More bad news about anti-inflammatory agents.

PMID- 18072103
TI  - The lexiconography of toxicology.

PMID- 18072104
TI  - The role of fat emulsion therapy in a rodent model of propranolol toxicity: a
      preliminary study.
AB  - INTRODUCTION: In animal models, lipid emulsion therapy has been shown to
      ameliorate toxicity from a number of lipid soluble agents. This preliminary study
      addresses the hypothesis that pretreatment with lipid emulsion protects against
      propranolol toxicity in rodents. METHODS: Ten spontaneously ventilating Rattus
      norvegicus rats were pretreated with either lipid emulsion or 0.9% normal saline
      before undergoing a constant infusion of propranolol until death. An
      electrocardiogram (ECG) sampling of heart rate and a QRS duration was performed
      at two-minute intervals until demise. RESULTS: There was no significant
      difference in lethal doses of propranolol between groups. Comparison of percent
      change in QRS prolongation and heart rate reduction was performed at 60% of the
      mean lethal dose in control animals. The percent change in QRS duration was
      reduced (from -0.9 to 17.3, p=0.016) in the intralipid pretreatment group.
      Attenuation of propranolol-induced bradycardia observed in the lipid emulsion
      group approached statistical significance (0% vs. 10.3%, p=0.06). INTERPRETATION:
      The results suggest that lipid emulsion may be effective in ameliorating
      propranolol toxicity in rats. Previous work gives reason to postulate a
      pharmacokinetic mechanism for this effect. The results represent encouraging
      exploratory work, and further work is planned to evaluate the role of lipid
      emulsion therapy in propranolol toxicity.

PMID- 18072105
TI  - Carisoprodol abuse in Texas, 1998-2003.
AB  - INTRODUCTION: Texas poison centers identified carisoprodol as a skeletal muscle
      relaxant that is subject to abuse, and this investigation explores the abuse
      reported by Texas poison centers. METHODS: This study used data from six Texas
      poison centers to describe the epidemiology of carisoprodol abuse and drug
      identification (ID) calls from 1998 to 2003. RESULTS: Drug ID and abuse calls
      were 217% higher in 2003 than in 1998. Although eastern and central Texas
      contains 43% of the state's population, this region reported 77% of all drug ID
      calls and 64% of abuse calls. For male patients, 51% of the calls were abuse
      calls and 37% were other human carisoprodol exposure calls. Patients from 13 to
      19 years of age accounted for 17% of abuse calls and 9% of other human exposure
      calls. Among those human exposure calls with a known medical outcome, a higher
      percentage of abuse calls involved minor effects while a greater proportion of
      other human exposure calls involved outcomes that ranged from moderate effects to
      death. CONCLUSIONS: Carisoprodol abuse is increasing in Texas and is
      substantially more common in the eastern part of the state. Carisoprodol abuse is
      much more likely, than other types of adverse carisoprodol exposures, to involve
      males and adolescents; and it less likely to involve adverse medical outcomes.

PMID- 18072106
TI  - Cadmium exposure: health hazards of silver cottage industry in developing
      countries.
AB  - In countries such as India, the silver jewelry industry is an important cottage
      industry. Silver is mixed with cadmium and then used to make silver jewelry.
      During this process there is a formation of cadmium fumes, and the workers inhale
      the fumes. Cadmium is a neurotoxic and nephrotoxic heavy metal, and there are no
      national policies to prevent exposure to such chemicals. We will present a case
      of cadmium induced peripheral neuropathy, nephropathy, and decreased bone
      density.

PMID- 18072107
TI  - Cerebrovascular accident following MDMA ingestion.

PMID- 18072108
TI  - Case files of the Medical Toxicology Fellowship Training Program at the
      Children's Hospital of Philadelphia: a pediatric exploratory sulfonylurea
      ingestion.

PMID- 18072110
TI  - Snakebites in the new millennium. Proceedings of a state-of-the-art symposium.
      October 21-13, 2005. Omaha, Nebraska, USA.

PMID- 18072111
TI  - Medical toxicology and public health: update on research and activities at the
      Centers for Disease Control and Prevention.

PMID- 18072112
TI  - The use of visual analog pain scales in black widow spider envenomation.

PMID- 18072113
TI  - Conflicts of interest: bias or boon?

PMID- 18072114
TI  - Resistant alcohol withdrawal: does an unexpectedly large sedative requirement
      identify these patients early?
AB  - INTRODUCTION: While most patients with alcohol withdrawal (AW) respond to
      standard treatment that includes doses of benzodiazepines, nutrition and good
      supportive care (non resistant alcohol withdrawal-NRAW), a subgroup may resist
      therapy (resistant alcohol withdrawal-RAW). This study describes a distinct group
      of AW patients, their sedative requirements, and hospital courses. METHODS: Over
      a period of 6 months, AW patients requiring 50 mg diazepam IV in the first hour
      were followed. We recorded admission indices and diazepam doses with vital signs
      at 1, 2, 3, 6, 12, and 24 hours. Patients were considered to have RAW if they
      required additional sedatives for control of symptoms and/or were having
      persistent abnormal vital signs despite the physicians' choices of therapy.
      RESULTS: Nineteen patients were enrolled; all had similar admission indices.
      While the 4 NRAW had normal vital signs within 3 hours, all 15 RAW patients had
      abnormal vital signs; 15 RAW patients required escalating diazepam doses--14
      required barbiturates, 7 were intubated, and 5 had hypotension. Comparing groups:
      interval and total diazepam doses were not different at 1,2, and 3 hours;
      interval doses at 6 and 12 hours, and total doses at 6, 12, and 24 hours were
      significantly different. CONCLUSIONS: RAW patients require large doses of
      benzodiazepine administration, additional sedatives, and undergo complicated
      hospitalizations.

PMID- 18072115
TI  - Factitious lithium toxicity secondary to lithium heparin-containing blood tubes.
AB  - INTRODUCTION: Lithium concentrations analyzed from blood collected in
      inappropriate tubes may lead to misdiagnosis and lead to unnecessary
      hospitalization and intervention. We sought to assess the magnitude of falsely
      elevated lithium levels in green top lithium heparin-containing blood tubes.
      METHODS: Serum lithium concentrations from two types of commonly used standard
      green top tubes were evaluated against a control tube. Blood samples obtained
      from 5 healthy volunteers who have never ingested pharmaceuticals containing
      lithium were aliquoted into a control serum separator tube (SST), a light green
      heparin-containing tube, and a dark green heparin tube at the following volumes:
      full draw, 2cc, and 1cc. Serum lithium levels in lithium heparin blood tubes were
      compared to standard blood tubes. RESULTS: All levels are reported as mmol/L.
      Mean serum lithium level for the control was 0.16 [range: 0.1-0.2]. Levels for
      the light-green tubes at full-draw, 2cc, and 1cc were 1.05 [1.0-1.1], 1.99 [1.68
      2.3], and 3.31 [2.8-4.2] respectively. Levels for the darkgreen tubes at full
      draw, 2cc, and 1cc were 1.07 [1.0-1.14], 2.35 [2.1-2.55], and 4.04 [3.8-4.4]
      respectively. CONCLUSIONS: Falsely elevated lithium levels may occur when using
      green-top lithium containing blood tubes and may contribute as much as 4 mmol/L
      to the level in tubes not completely filled.

PMID- 18072116
TI  - Bacillus spores in the mail: "ironing" out the anthrax problem.
AB  - INTRODUCTION: Following a terrorist release of Bacillus anthracis spores through
      the U.S. Postal Service, it was suggested that decontamination of spores in mail
      envelopes could be accomplished at home by utilizing the steam heat from a
      household iron. This study investigated the use of a standard household iron, in
      a dry heat mode, for sterilizing mail envelopes laced with bacterial spores.
      METHODS: The Bacillus subtilis var. niger spore, a more heat resistant spore, was
      used as a surrogate for B. Anthracis spores. Standard mail envelopes containing
      2.1 x 10(6) spores were sealed and subjected to various levels of dry heat from a
      standard household iron for periods of 5, 10, and 15 minutes. Envelope contents
      were then cultured in soy broth for seven days to detect any bacterial growth,
      and in addition envelopes and contents were visually inspected for evidence of
      damage and readability of words. RESULTS: At a temperature range of 160.01
      degrees C - 204.5 degrees C for a period of 5 minutes, B. subtilis var. niger
      spores were effectively sterilized and, at 7 days, no bacterial growth was
      observed. No gross evidence of envelope damage was observed and the legibility of
      words was not compromised. CONCLUSIONS: Dry heat from a common household iron is
      capable of destroying Bacillus spores in mailing envelopes without grossly
      altering the envelope or affecting the legibility of words.

PMID- 18072117
TI  - An investigation of flumazenil to antagonize gamma-hydroxybutyrate intoxication
      in a murine model.
AB  - OBJECTIVE: Prior animal studies have suggested that flumazenil may blunt GHB's
      sedative-hypnotic affects. We hypothesized that flumazenil would decrease the
      affects of GHB in a murine model of intoxication. METHODS: We performed a
      controlled, pilot experiment using 32 mice divided into 3 groups. All mice
      received intraperitoneal injections of GHB (1.5 g/kg). Group I received sham
      injections at time 0, and then GHB at 5 minutes. Group II received flumazenil
      (0.3 mg/kg) at time 0, and then GHB at 5 minutes. Group III received sham
      injection at time 0, then GHB at 5 minutes, and then 4 escalating flumazenil
      doses administered at 3-minute intervals (0.003 to 1 mg/kg). We measured certain
      functions: time to loss/recovery of righting reflexes (RR), time to
      sprawl/recovery of sprawl (postural tone [PT]), and death. RESULTS: There were
      statistically significant delays in the loss of PT and shortened recovery time to
      RR in pre-treated mice (group II) versus controls (group I). There were no
      differences in group III versus group I for any outcome parameters. CONCLUSIONS:
      In this model, pre-dosing flumazenil prior to GHB administration delayed clinical
      intoxication.

PMID- 18072118
TI  - Nitrous oxide "whippit" abuse presenting with cobalamin responsive psychosis.
AB  - INTRODUCTION: Nitrous oxide is a commonly abused inhalant drug. It is known to
      precipitate vitamin B12 deficiency when used chronically and acutely, especially
      in people having marginal vitamin B12 reserve. CASE REPORT: We are presenting a
      case of nitrous oxide "whippit" abuse in a thirty-three-year-old male with
      bizarre behavior and delusions. The patient had low normal levels of vitamin B12
      (202 pg/ml), but he had markedly high methylmalonyl CoA (1078 nmol/L) and
      homocysteine (48.4 mcmol/L). Treatment with intramuscular cobalamin led to a
      resolution of his psychosis. DISCUSSION: This case report highlights the need to
      consider vitamin B12 deficiency in patients who arrive at a hospital with
      psychiatric manifestations and who report having a history of nitrous oxide
      exposure or abuse in the recent or remote past. A review of the literature on the
      neuropsychological manifestations of vitamin B12 deficiency is provided.

PMID- 18072119
TI  - Case files of the medical toxicology fellowship training program at the New York
      city poison control center: hypotensive death--therapeutic complication or
      suicide?

PMID- 18072120
TI  - Recipe for disaster: Mexican methamphetamine.

PMID- 18072121
TI  - Medical toxicology and public health - update on research and activities at the
      Centers for Disease Control and Prevention and the Agency for Toxic Substances
      and Disease Registry.

PMID- 18072123
TI  - Off-label: just what the doctor ordered.

PMID- 18072124
TI  - Noninvasive measurement of carbon monoxide levels in ED patients with headache.
AB  - OBJECTIVES: Carbon Monoxide (CO), the third most common cause of acute poisoning
      death, is easily overlooked in the emergency department (ED). Nonspecific
      complaints such as headache, weakness, or malaise may easily result in
      misdiagnosis. The objectives of this study are to determine the frequency of CO
      poisoning in patients presenting to the ED complaining of headaches and to
      determine the feasibility of using noninvasive CO analyzers as a screening tool.
      METHODS: This prospective controlled study examined, during the winter months,
      adult patients presenting with a complaint of atraumatic, afebrile headaches. All
      subjects submitted a sample for a CO breath analyzer. Participants with elevated
      carboxyhemoglobin (COHb) levels (nonsmokers >2%, smokers >5%) underwent venous
      COHb testing. Control patients, without headaches, presenting to the ED were
      similarly studied. RESULTS: We enrolled 170 subjects and 98 controls. Of the 170
      subjects, 12 (7.1%) had elevated COHb levels confirmed by venous COHb levels. Of
      the 98 controls, 1 (1.0%) had an elevated COHb level (p < 0.05). There were no
      differences in demographic factors between the two groups (p > 0.16).
      CONCLUSIONS: Noninvasive measurement of CO levels in ED patients with headaches
      is rapid and specific. During winter months, elevated CO levels are present in
      over 7% of ED patients with headaches.

PMID- 18072125
TI  - The effect of IM droperidol on driving performance.
AB  - OBJECTIVES: Droperidol (DROP) is used in the emergency department (ED) for
      several indications, but its effect on psychomotor performance is unclear. The
      purpose of this study was to evaluate the effects of DROP, 2.5 mg intramuscular
      (IM), on driving performance. METHODS: This was a randomized, double-blinded, two
      period, placebo-controlled crossover trial that utilized a standard driver
      training program with computerized scoring. We solicited 20 paid volunteers who
      were pre-screened with a 12-lead EKG to evaluate QT length. For the first driving
      simulation, subjects were randomly assigned to receive either 2.5 mg of DROP IM
      or an equal volume of normal saline (NS). At least 72 hours later, the same
      subjects participated in a second driving simulation. For the second driving
      simulation, the assignment of DROP, 2.5 mg IM, or normal saline was reversed: (If
      a subject received DROP, 2.5 mg IM, in the first simulation, the subject received
      normal saline in the second simulation; conversely, if a subject received normal
      saline in the first simulation, the subject received DROP, 2.5 mg IM, in the
      second simulation). Thirty minutes later, participants drove the 20-minute
      simulation and received an average score based on the errors made in 4
      categories: accelerating, braking, steering, and signaling. Post-testing,
      participants evaluated their degree of drowsiness and driving impairment using a
      visual analog scale and compared their perception of impairment to that caused by
      alcohol ingestion. Data were analyzed using analysis-of-variance, Pearson chi
      square and Fischer's exact test with alpha set at p = 0.05. RESULTS: Twenty
      subjects (11 males and 9 females) completed the protocol. The mean age was 30
      years with a range of 20 to 46 years, and the mean weight was 80 kg. The mean
      driving experience was 12 years. Participants who received DROP felt
      significantly drowsier (38.6 mm +/- 9.0) than those receiving NS (13.2 mm +/-
      9.0), the mean difference was 25.4 mm p = .009. Subjects receiving DROP were also
      more likely to feel that their driving would be impaired as rated on the VAS
      (DROP: 34.6 +/- 5.2; NS: 3.2 +/- 5.2; p = .0005), and DROP subjects reported
      impairment equivalent to 1-4 drinks more frequently than those receiving placebo
      (61% vs. 16.7%, p < .001). These subjective feelings of impairment were confirmed
      by their driving performance on the simulator. The mean driving score, using the
      driving simulator, was 68.8% with DROP vs. 73.6% with NS; p = .013. CONCLUSIONS:
      Subjects receiving modest doses of IM DROP report increased perceptions of
      drowsiness, driving impairment, and intoxication; these perceptions are confirmed
      on objective testing.

PMID- 18072126
TI  - Publication of abstracts presented at 2001 NAACT.
AB  - INTRODUCTION: The timely and formal publication of material presented as
      abstracts at national meetings is critical to the dissemination of new
      information to the medical community. We designed a retrospective study to
      evaluate the publication rates of abstracts presented at a recent national
      toxicology conference. In addition, we attempted to determine whether readily
      identifiable characteristics could predict a greater likelihood of publication.
      METHODS: In June of 2004, we reviewed 237 abstracts from the 2001 North American
      Congress of Clinical Toxicology (NACCT). Abstracts were classified according to
      methodology and content. We then searched Medline, using PubMed, to determine the
      publication of each abstract. RESULTS: Fifty-seven of 237 abstracts (24.1%) were
      subsequently published in peer reviewed journals. There was no statistically
      significant difference in the rate of publication when abstracts were categorized
      with respect to methodology. When categorized with respect to content, abstracts
      related to natural toxins had a higher publication rate (41.2%; p < 0.05).
      CONCLUSIONS: Three years after presenting abstracts at the 2001 NACCT meeting,
      the majority of abstracts remain unpublished. This is a lower rate than noted by
      other specialty medical societies.

PMID- 18072127
TI  - Pattern of dipyrone exposure in Texas, 1998 to 2004.
AB  - INTRODUCTION: Dipyrone is an analgesic and antipyretic agent. The purpose of this
      study was to describe the pattern of dipyrone exposures reported to poison
      centers. METHODS: Human dipyrone exposures reported to 6 Texas poison centers
      from 1998 to 2004 were identified. Isolated and non-isolated cases were compared
      with respect to various factors. RESULTS: When compared to the Census, dipyrone
      exposures were significantly more likely to have been reported from regions
      closer to the Mexican border (53% vs 9%). Of 81 dipyrone exposures, 52 (64%) were
      isolated and 29 (36%) were non-isolated. Most of the dipyrone exposures occurred
      at the patient's own residence (72/76 or 95%) and the patients were more likely
      to be female (54/81 or 67%). Although the majority of both types of dipyrone
      exposures were adults (47/78 or 60%), children, less than 6 years of age,
      accounted for a higher proportion of isolated exposures (33% vs 10%) while a
      higher proportion of non-isolated exposures involved older children (28% vs 8%).
      Twenty-two percent (11/51) of isolated cases were intentional while 59% (17/29)
      of non-isolated cases were intentional. Of those cases with a known medical
      outcome, the medical outcome was no adverse clinical effect for 76% (16/21) of
      isolated exposures and 42% (8/19) of non-isolated exposures. The specific adverse
      clinical effects reported for isolated exposures were primarily neurological (n =
      6), gastrointestinal (n = 4), and dermal (n = 3). The most frequently reported
      treatment for isolated exposures was some form of decontamination (n = 11).
      CONCLUSIONS: Isolated and non-isolated dipyrone exposures varied with respect to
      patient age, exposure reason, management site, medical outcome.

PMID- 18072128
TI  - Phentolamine therapy for cocaine-association acute coronary syndrome (CAACS).
AB  - INTRODUCTION: The emergency department (ED) evaluation of cocaine-associated
      acute coronary syndrome (CAACS) is often a diagnostic and therapeutic challenge.
      CASE REPORT: We are reporting on the treatment of a patient with cocaine
      associated acute coronary syndrome (CAACS) who did not benefit from standard
      therapy, but who eventually responded positively to phentolamine, an alpha
      adrenergic receptor antagonist. DISCUSSION: This report should encourage
      physicians to add phentolamine to their pharmacotherapeutic armamentarium in the
      treatment of CAACS.

PMID- 18072129
TI  - Dilemmas downstream from the Songhua River spill.

PMID- 18072130
TI  - Medical toxicology and public health--update on research and activities at the
      Centers for Disease Control and Prevention and the Agency for Toxic Substances
      and Disease Registry.

PMID- 18072132
TI  - The power of the case report.

PMID- 18072134
TI  - Effects of amiodarone in a swine model of nortriptyline [corrected] toxicity.
AB  - OBJECTIVES: Antiarrhythmics can have devastating effects in cardiotoxic
      poisonings. Amiodarone is recommended for treatment of wide complex tachycardia,
      but its hemodynamic effects in wide complex tachycardia induced by tricyclic
      antidepressant poisoning are unknown. The objective of this study was to compare
      the effects of sodium bicarbonate, amiodarone, and normal saline in treating wide
      complex tachycardia secondary to nortriptyline poisoning. METHODS: This unblended
      randomized controlled animal study involved 18 anesthetized, intubated pigs with
      arterial and venous lines. Nortriptyline (2 mg/mL) was infused at 20 mg/min until
      the onset of toxicity, defined as a systolic blood pressure < or =50 mmHg or QRS
      > or =120 ms. At that point, the pigs were randomized into three groups of six.
      Group I received 0.9% normal saline, 10 ml/kg. Group II received hypertonic
      sodium bicarbonate, 1 mEq/kg. Group III received amiodarone, 15 mg/kg. The pigs
      were observed until death or survival at 60 minutes. RESULTS: After treatment,
      the changes in QRS were as follows: Group I, -2.0 ms; Group II, -33.0 ms; Group
      III, -21.7 ms. ANOVA demonstrated no significant difference between the groups (p
      = 0.28). Mean arterial pressures 10 minutes after treatment were as follows:
      Group I, 19.4 mmHg; Group II, 23.7 mmHg; Group III, 12.5 mmHg. Based on ANOVA,
      there was no significant difference between any of the groups (p = 0.50).
      CONCLUSIONS: In this model of nortriptyline poisoning, the administration of
      amiodarone to correct wide complex tachycardia did not have a harmful effect.

PMID- 18072133
TI  - Reactivation of sarin-inhibited pig brain acetylcholinesterase using oxime
      antidotes.
AB  - INTRODUCTION: Organophosphorus nerve agents inhibit the enzyme,
      acetylcholinesterase (AChE; EC 3.1.1.7). AChE reactivators (also known as oximes)
      are generally used for the reactivation of an inhibited enzyme. METHODS: Two new
      AChE reactivators--K033 and K027--were tested for their in vitro reactivation of
      sarin-inhibited pig-brain AChE. Their reactivation potencies were compared with
      the commercially available AChE reactivators, pralidoxime, obidoxime, and HI-6.
      RESULTS: Of the oximes tested, the newly developed oxime K027 achieved the
      highest reactivation potency (100%; concentration of the oxime -10(-2) M).
      However, oxime HI-6 (33%) and obidoxime (23%) seem to be the best AChE
      reactivators for human relevant doses (10(-4) M and lower). CONCLUSION: For human
      relevant doses, newly developed oximes (K027 and K033) do not surpass the
      reactivation potency of the most promising oxime, HI-6.

PMID- 18072135
TI  - Cardioactive steroid poisoning: a comparison of plant- and animal-derived
      compounds.
AB  - INTRODUCTION: Cardioactive steroids (CASs) are found in plants, animals, and
      insects. Their affinity for Na+-K+ ATPase is attenuated by the type of lactone at
      carbon 17 (C17) of the steroid backbone: those with 5-membered lactone rings, or
      cardenolides, are derived mostly from plants with 6-membered rings or from
      animals with bufadienolides. A systematic review of CAS poisoning was performed
      to compare the mortality rate of cardenolides and bufadienolides. METHODS:
      MEDLINE was searched for articles using commonly reported names of CASs, and
      keywords were limited to human cases only. We searched cases from 1982 to 2003,
      so that supportive care was similar and digoxin-specific Fab was available.
      Identified reports of CAS poisoning were read to exclude cases involving licensed
      pharmaceuticals. Inclusion criteria included hyperkalemia, gastrointestinal
      symptoms, electrocardiographic evidence of CAS toxicity, digoxin serum
      concentration, or history of exposure to a substance containing a CAS. Clinical
      data was collected, including information about treatment with digoxin-specific
      Fab and treatment outcome. RESULTS: Fifty-nine articles, describing 924 patients,
      were identified. Eight hundred ninety-seven patients (97%) ingested a CAS with a
      5-membered lactone ring, and mortality was 6% (n = 54). Twenty-seven patients
      (2.9%) ingested a CAS with a 6-membered lactone ring, and mortality was 29.6% (n
      = 8). The difference in mortality rates was statistically significant (p < 0.001,
      [X2]). CASs with 6-member rings accounted for the highest percentage of
      nonsuicidal exposures. CONCLUSION: Although cardenolides accounted for the
      majority of exposures, bufadienolides were five times more lethal than
      cardenolides.

PMID- 18072137
TI  - Seizures in a pediatric patient with a tiagabine overdose.
AB  - INTRODUCTION: Tiagabine (TGB) is a novel antiepileptic that decreases GABA
      uptake. The literature contains one report of an adult with epilepsy who ingested
      up to 1 gram of TGB and developed status epilepticus. We reported on a pediatric
      patient who ingested significantly less TGB but still developed tonic-clonic
      seizures. CASE REPORT: A previously healthy, 13 kg, two-year-old girl developed
      generalized tonic-clonic seizure activity at home approximately 1 hour after
      ingesting 90 mg of her grandmother's TGB (forty five 2 mg tablets). At the
      hospital she had two 5 minute seizures at 1.5 and 3.5 hours post ingestion. Her
      serum TGB levels were 530 and 130 ng/ml approximately 5 and 11 hours post
      ingestion (5-70 ng/ml trough levels with most probable range for seizure
      control). She was discharged 27 hours post ingestion, and she was in good
      condition. CONCLUSION: An overdose of TGB, a novel anti-epileptic, can cause
      convulsive seizures.

PMID- 18072136
TI  - Intramuscular ophthalmic homatropine vs. atropine to prevent lethality in rates
      with dichlorvos poisoning.
AB  - INTRODUCTION: Most hospitals lack a sufficient supply of atropine to treat,
      simultaneously, patients poisoned with multiple organophosphorous compound (OC)
      or nerve agent. The presence of a ubiquitous alternate antidote would prove
      useful if mass poisoning occurred. Our objective was to evaluate the effect of
      ophthalmic homatropine (Isopto Homatropine 5%) on survivability in a rat model of
      significant, acute OC poisoning. METHODS: Sprague-Dawley rats were randomized to
      one of five pre-treatment groups (N = 10 per group). Prior to experimentation,
      animals were pre-treated with intramuscular (IM) injections of either atropine 5
      mg/kg, atropine 10 mg/kg, homatropine 10 mg/kg, or homatropine 20 mg/kg. The
      control group received 0.3 mL normal saline IM. Five minutes later, 25 mg/kg of
      dichlorvos was subcutaneously administered. Mortality rates were compared using
      Fisher's Exact test. Kaplan-Meier survival curves with Logrank analysis was also
      performed. If alive at 120 minutes, survival was assumed, and the study was
      terminated. RESULTS: All rats pre-treated with normal saline, atropine 5 mg/kg,
      and homatropine 10 mg/kg died. Survival in the homatropine (20 mg/kg) and
      atropine (10 mg/kg) groups was 30% and 40% respectively. Times to death ranged
      between 4 and 12 minutes. Overall comparison of time to death revealed a
      statistically significant improvement for groups pre-treated with homatropine (20
      mg/kg) and atropine (10 mg/kg). CONCLUSIONS: Pre-treatment with homatropine (20
      mg/kg) was comparable with atropine (10 mg/kg) in preventing lethality in this
      rat model of acute OC poisoning.

PMID- 18072138
TI  - Case files of the University of Massachusetts fellowship in medical toxicology:
      three patients with an industrial radiography source exposure.

PMID- 18072139
TI  - Medical toxicology and public health: update on research and activities at the
      Centers for Disease Control and Prevention and the Agency for Toxic Substances
      and Disease Registry.

PMID- 18072140
TI  - ACMT position statement: the Iom report on thimerosal and autism.

PMID- 18072141
TI  - S.I. for dummies.

PMID- 18072142
TI  - Weight gain associated with chronic exposure to chlorpyrifos in rats.
AB  - OBJECTIVE: This work exposed rats to low levels of the organophosphate
      insecticide chlorpyrifos and monitored for toxic effects, including weight gain.
      METHODS: Rats received either a subcutaneous injection of chlorpyrifos, 5
      mg/kg/day, or an equal volume of vehicle daily for 4 months. Subjects were
      observed for 30 minutes after injection for signs of acute toxicity. Body weights
      were recorded at baseline, 2 months, 3 months, and 4 months. At the end of the
      experiment, the weights of hearts, medial lobe of the livers, peri-nephric fat
      pads, and gastrocnemius muscles were recorded. Effects of chlorpyrifos on
      adipocyte differentiation in culture were studied. Results were compared using
      RMANOVA. RESULTS: No signs of acute cholinergic toxicity were observed after
      injections in any subject. Rats in the 5 mg/kg group were significantly heavier
      than those in the control group by 2 months (335.7 +/- 16.7 g vs. 318.6 +/- 15.8
      g; p = 0.034). This difference increased at 3 months (350.1 +/- 16.4 g vs. 322.3
      +/- 21.3 g p = 0.006) and 4 months (374.4 +/- 22.2 g vs. 340.2 +/- 25.2 g p =
      0.006). At 4 months, the weights of the perinephric fat pads were significantly
      increased in the chlorpyrifos group relative to controls (2.867 + 0.516 vs. 1.130
      + 0.171, p = 0.0039). The two groups showed no weight differences between hearts,
      livers, and gastrocnemius muscles. Chlorpyrifos did not affect adipocyte
      differentiation in tissue culture. CONCLUSIONS: Chronic exposure to chlorpyrifos
      at 5 mg/kg/day caused an increase in rat body weight when compared to controls.
      This increase was in adipose tissue. Chlorpyrifos did not induce differentiation
      of adipocytes in culture.

PMID- 18072143
TI  - Pyrethrin and pyrethroid exposures in the United States: a longitudinal analysis
      of incidents reported to poison centers.
AB  - INTRODUCTION: Citing the Food Quality Protection Act, the US Environmental
      Protection Agency (EPA) decided to phase out and eliminate organophosphate
      insecticide use in residential environments. The phase out process spanned from
      2000 to 2005, and it may have resulted in increased consumer use of insecticides
      containing other active ingredients. This study utilized data from the national
      Poison Control Center to assess possible changes in exposure incidents involving
      pyrethrin and pyrethroid insecticides during the phase out of organophosphates
      from residential uses. METHODS: We extracted pyrethrin and pyrethroid insecticide
      exposure data from the American Association of Poison Control Centers Toxic
      Exposure Surveillance System (TESS) annual reports from 2000 to 2005. We examined
      pyrethrin and pyrethroid incidents by total exposures for each year, and we
      stratified exposures by age range, reason, number of cases treated in a health
      care facility, and medical outcome. Cases were examined as a proportion of all
      insecticide exposures. We calculated the annual incidence rates for exposures
      involving pyrethrin and pyrethroid insecticides of the population served.
      RESULTS: Pyrethrin and pyrethroid exposures increased annually in number and as a
      percentage of all insecticide exposure incidents. The increase in cases was
      observed for all age categories and exposure reasons. A statistically significant
      correlation was observed between advancing years (2000-2005) and the number of
      pyrethrin and pyrethroid incidents (p<.01). While the number of incidents treated
      in a health care facility increased annually during the study period, the
      proportion was constant (0.185 +/- 0.012) over the six year period. During the
      study period, the incidence rate for pyrethrin and pyrethroid exposures increased
      each year. 44% of all medical outcomes data was recorded, and the majority of
      outcomes resulted in no symptoms (37%) or minor symptoms (53%). CONCLUSION: TESS
      data showed a clear increase in cases involving pyrethrins and pyrethroids. The
      increase was temporally associated with the phase out of organophosphates from
      residential uses. In the future, medical toxicologists and poison control center
      personnel should be prepared to respond to an increasing number of pyrethrin and
      pyrethroid insecticide exposures.

PMID- 18072144
TI  - The feasibility of administration of activated charcoal with respect to current
      practice guidelines in emergency department patients.
AB  - OBJECTIVE: The American Academy of Clinical Toxicology, European Association of
      Poisons Centres, and Clinical Toxicologists recommend administration of activated
      charcoal (AC) within one-hour of an acute toxic ingestion [1]. Our poison control
      center periodically and upon request faxes an abbreviated protocol to hospital
      emergency departments, reminding physicians of these current AC recommendations.
      This study was conducted to describe how often patients present within the one
      hour time frame and how often the guidelines in the above position statement are
      being followed. METHODS: Following a brief training of systematic chart review,
      reviewers blinded to the purpose of the study completed a standardized data
      collection sheet. Three years after publication of these consensus statements, a
      period of 3 consecutive years of poison center patient encounters were reviewed.
      Recorded data included age, outcomes, and time to administration of charcoal.
      RESULTS: Approximately 150,000 reported toxic exposures were reviewed, of which
      16,914 patients of acute ingestions presented to a health care facility. The mean
      age of the group that presented was 25 years [range 1 month-87 years]. A total of
      2,700 (16%) patients that presented were within 60 minutes of an acute overdose
      and all were administered AC in accordance with the recommended guidelines.
      Interestingly, pre-hospital personnel administered AC within 60 minutes to 762
      (28% of 2,700) patients. Correspondingly, 14,214 (84%) patients presented more
      than 60 minutes after an acute overdose. Of this latter group AC was withheld in
      341 (2.4% of 14,214) patients, and 13,873 (97.6% of 14,214) patients received
      charcoal despite having arrived more than 60 minutes after ingestion. The mean
      time to the first administration of AC in this latter group was 225 minutes
      [range of 61-2160 minutes] following ingestion. CONCLUSIONS: Only a small
      percentage of patients treated for an acute overdose (16%) present within 60
      minutes and are given charcoal according to the current guidelines. A large
      subset of these patients (28%) is given AC in a pre-hospital setting. Few
      patients presenting to a health care provider after an acute toxic ingestion are
      treated in accordance with the current recommendations for activated charcoal.

PMID- 18072145
TI  - Pediatric sex group differences in location of snakebite injuries requiring
      antivenom therapy.
AB  - OBJECTIVE: The objective of this study is to examine the patterns of snakebite
      injury in pediatric patients that require antivenom therapy and to evaluate
      whether and when sex group differences exist. METHODS: We performed a nationwide,
      multicenter, retrospective evaluation of 24 regional poison centers from 2002 and
      through 2004 of data for antivenom therapy for Crotaline snakebites. Data points
      abstracted included the age of the victim, sex of the victim, and location of
      bite. We calculated contingency tables of the data with statistical significance
      by Fisher's exact test. RESULTS: We evaluated 204 records that involved pediatric
      patients; 3 of the patients had no recorded age. In 16 of the records, the bite
      location was not documented (2 children and 1 unknown age) or was listed as
      head/neck (1 child). These records were not included in the data analysis. There
      were bites in 136 males and 65 females. Males were more likely than females to
      suffer an injury to the upper extremity (56.6% vs. 26.2%; p<0.01). Males were
      more likely to suffer injuries to the upper extremity in all age groups (p <0.05)
      except for the group aged 10 through 12 years; in the group aged 10 through 12,
      we did not see significant differences between the sexes (p=0.729). Males are
      more likely to suffer an upper extremity bite with increasing age (p=0.029),
      while females showed no significant change in the location of bites (p=0.223).
      CONCLUSION: Male children were more likely than female children to suffer
      Crotaline snakebites that required antivenom therapy. In this population,
      significant differences between locations of snakebites were found. Males were
      more likely than females to be bitten in the upper extremities. This difference
      appears as early as 1 to 4 years of age.

PMID- 18072146
TI  - Insulin & C-peptide levels in sulfonylurea-induced hypoglycemia: a systematic
      review.
AB  - OBJECTIVES: We will describe insulin and C-peptide levels observed in
      sulfonylurea-induced hypoglycemia and determine whether these levels differed if
      obtained before or after hypoglycemic therapy. METHODS: We performed a systematic
      review of the English literature to identify Medline articles containing "sets"
      (glucose <60 mg/dL with insulin and C-peptide levels). These "sets" were
      categorized as being obtained BEFORE, AFTER, or UNKNOWN with respect to
      hypoglycemic therapy. RESULTS: 22 articles, 76 patients, and 97 "sets" were
      included. Mean glucose (mg/dL), insulin (muIU/mL), and C-peptide (ng/mL) for all
      "sets' were 28.6 (+/-12.6; 26.1 to 31.2), 54.4 (+/-126.3; 28.3 to 80.5), 7.2 (+/
      6.2; 5.9 to 8.5). The BEFORE measures were 24.3 (+/-7.3; 18.7 to 30.0), 36.6 (+/
      26.2; 16.5 to 56.7), 5.4 (+/-4.6; 1.5 to 9.2). The AFTER measures were 33.1 (+/
      9.8; 28.2 to 38.0), 126.7 (+/-278.1; 0 to 265.0), 10.3 (+/-10.5; 5.1 to 15.4).
      The UNKNOWN measures were 28.0 (+/-13.5; 24.7 to 31.3), 37.1 (+/-21.8; 31.7 to
      42.5), 6.5 (+/-4.3; 5.4 to 7.6). Only one "set" (glucose 49 mg/dL) had insulin
      <3.9 muIU/mL and C-peptide <1.4 ng/mL. CONCLUSIONS: Insulin > or =3.9 muIU/mL, C
      peptide > or =1.4 ng/mL, and glucose <49 mg/dl are consistent with sulfonylurea
      induced hypoglycemia. BEFORE levels were lower, but they were consistent with
      sulfonylurea-induced hypoglycemia.

PMID- 18072147
TI  - Profound metabolic acidosis and oxoprolinuria in an adult.
AB  - INTRODUCTION: Profound metabolic acidosis in critically ill adults sometimes
      remains unexplained despite extensive evaluation. CASE REPORT: A 58-year-old
      female presented in a confused state to the emergency department; she had been
      confused for several days. Laboratory evaluation revealed a high anion gap
      metabolic acidosis and modestly elevated acetaminophen level. Lactic acid was
      only modestly elevated. There was no evidence of ketoacids, salicylate, methanol,
      or ethylene glycol. A urine sample submitted on day 1 of hospitalization revealed
      a markedly elevated level of 5-oxoproline. DISCUSSION: Originally described in
      children with an inherited defect of glutathione synthetase, 5-oxoproline is an
      unusual cause of metabolic acidosis. More recently this disturbance has been
      recognized in critically ill adults without a recognized inherited metabolic
      disorder. In most of these cases there has been the concomitant use of
      acetaminophen. Any causal relationship between acetaminophen and this disturbance
      is speculative. CONCLUSION: In critically ill adults with unexplained metabolic
      acidosis, 5-Oxoproline should be considered in the differential.

PMID- 18072148
TI  - Ethylene glycol ingestion treated only with fomepizole.
AB  - INTRODUCTION: Ethylene glycol is a widely used chemical that is capable of
      causing significant injury if ingested. Treatment for ethylene glycol poisoning
      typically includes basic supportive care, alcohol dehydrogenase inhibition, and
      hemodialysis. Recent data have suggested that hemodialysis may not be necessary
      for cases of ethylene glycol poisoning that can be treated with fomepizole as
      blocking therapy before acidosis or renal dysfunction develops. CASE REPORT: A 33
      year-old man presented to the emergency department 1 hour after drinking
      approximately 1/2 gallon of ethylene glycol antifreeze and an unknown quantity of
      beer. On arrival he was mildly inebriated but otherwise displayed no other
      features of ethylene glycol poisoning. Fomepizole therapy was initiated and
      initial laboratory studies later revealed an osmol gap of 157 mOsm and an
      ethylene glycol concentration of 706 mg/dL. Nephrology and toxicology services
      were consulted. Over the next 3 days, fomepizole therapy was continued while the
      patient's acid-base status and renal function were closely monitored. No evidence
      of acid-base abnormalities or renal impairment was ever observed and the patient
      was discharged to psychiatric care on the fourth hospital day. DISCUSSION: This
      report describes the case of a patient who presented soon after a massive
      ingestion of ethylene glycol with very high serum concentrations. He was
      successfully treated using fomepizole and basic supportive care. Our patient
      developed neither renal insufficiency nor metabolic acidosis. His concomitant
      ethanol consumption, early presentation, and treatment likely contributed to his
      favorable outcome. This case report underscores the effectiveness of supportive
      care and fomepizole in the treatment of ethylene glycol poisoning.

PMID- 18072150
TI  - Medical toxicology and public health--update on research and activities at the
      Centers for Disease Control and Prevention, and the Agency for Toxic Substances
      and Disease Registry.

PMID- 18072149
TI  - Case files of the Children's Hospital of Michigan Regional Poison Control Center:
      the use of carnitine for the management of acute valproic acid toxicity.

PMID- 18072151
TI  - The effect of amifostine, a cytoprotective agent, on paraquat toxicity in mice.
AB  - BACKGROUND: Paraquat (PQ) is a highly poisonous herbicide with a variety of toxic
      effects, most notably pulmonary fibrosis. In alveolar epithelial cells, it is
      converted to a PQ radical and subsequently generates other reactive species
      resulting in lipid peroxidation and cell destruction. Amifostine is a
      thiophosphate prodrug approved by the FDA for the prevention of toxicities
      associated with cisplatin and therapeutic radiation. When amifostine is converted
      to an active metabolite (WR-1065), it functions as an oxygen and DNA radical
      scavenger that has been shown to protect against lipoperoxidation. The aim of
      this study was to determine whether amifostine improves survival or lung injury
      resulting from PQ toxicity. METHODS: Swiss mice (n = 23 per group) were given an
      approximate LD75 dose of PQ intraperitoneal (60 mg/kg). Thirty minutes prior to
      PQ injection, group 1 was pretreated with 200 mg/kg of amifostine subcutaneously
      (s.c.). Subsequent doses of amifostine at 75 mg/kg were administered 4 hours
      after PQ injection, and injections continued every 8 hours for a total of 6 doses
      (cumulative dose: 575 mg/kg). Four hours after PQ injection, group 2 received 200
      mg/kg of amifostine subcutaneously. Subsequent doses of amifostine at 75 mg/kg
      were administered every 8 hours (cumulative dose: 575 mg/kg). Four hours after PQ
      injection, group 3 received 100 mg/kg of amifostine subcutaneously. Subsequent
      doses of amifostine at 30 mg/kg were administered every 8 hours (cumulative dose:
      250 mg/kg). Group 4 received equivolume injections of sterile 0.9% saline s.c. at
      the same time intervals. We removed lungs from all mice for histologic analysis
      and injury scoring. RESULTS: The number of surviving mice in groups 1, 2, 3, and
      4 were 17, 18, 17, and 17 respectively. The Kaplan-Meier with log rank analysis
      showed no differences in survival. Lung injury scores did not differ between
      treatment groups and the control group for either dead or surviving mice.
      CONCLUSION: Amifostine does not appear to improve survival or lung injury due to
      PQ toxicity at the doses administered.

PMID- 18072152
TI  - Designing a gamma hydroxybutyrate (GHB) structured telephone-administered survey
      instrument.
AB  - INTRODUCTION: As part of a larger study assessing the covariates and outcomes of
      GHB use, we developed a telephone-survey instrument for hospitalized GHB exposed
      patients identified through poison control center surveillance and for self
      identified GHB users recruited from the general public. METHODS: We used an
      iterative review process with an interdisciplinary team, including pharmacists, a
      physician, and a medical anthropologist. In designing the structured, telephone
      survey instrument, we prioritized inclusion of validated, drug-specific, and
      generic questionnaire batteries or individual items related to GHB or to other
      drugs of abuse. Only one published survey instrument specific to GHB use was
      identified, which we extensively expanded and modified. We also developed a
      number of GHB-specific items new to this survey. Finally, we included items from
      the National Survey on Drug Use & Health, CAGE questionnaire items on alcohol
      abuse, the SF-12 instrument, and selected National Health Interview items.
      RESULTS: The final questionnaire consisted of 272 content items, the majority of
      which required simple yes or no responses. The bulk of the items (74%) were GHB
      specific. The questionnaire was easily administered using computer-assisted
      telephone interview (CATI) software. A total of 131 interviews were administered
      with a mean administration time of 33+/-10 minutes. The instrument can also be
      used in other interview formats. CONCLUSION: Developing a successful
      questionnaire calls for a multidisciplinary and systematic process. Structured,
      telephone administered surveys are particularly suited to expand and explore the
      basic information obtained by poison centers for case management.

PMID- 18072153
TI  - Evolving epidemiology of drug-induced seizures reported to a Poison Control
      Center System.
AB  - INTRODUCTION: We sought to determine whether or not the causes and consequences
      of drug-induced seizures have changed in the last decade. METHODS: We conducted a
      retrospective review of all calls to the California Poison Control System in 2003
      in which seizures occurred in association with poisoning or drug intoxication. We
      reviewed the poison center chart of each case to determine the drug(s) involved,
      the type of seizures, and the medical outcome. We compared the cause of reported
      seizures to that found in previous investigations. RESULTS: 386 cases were
      evaluated and related to poisoning or drug intoxication. The leading causes of
      seizures were bupropion (89 cases, 23%), diphenhydramine (32 cases, 8.3%),
      tricyclic antidepressants (30 cases, 7.7%), tramadol (29 cases, 7.5%),
      amphetamines (27 cases, 6.9%), isoniazid (23 cases, 5.9%), and venlafaxine (23
      cases, 5.9%). Since 1993, there was a statistically significant increase in
      antidepressant related seizures but a decrease in TCA and cocaine related
      seizures. In 265 patients (68.6%) only a single seizure was reported, while 3.6%
      (14 cases) reported status epilepticus. Two-thirds (65.5%) of the cases involved
      suicide attempts and 14.8% the direct result of drug abuse. There were 7 deaths.
      Of the 7 deaths, 4 people had significant hyperthermia. There was a statistically
      significant increased risk of death associated with stimulant exposure.
      CONCLUSION: While tricyclic antidepressants, antihistamines, stimulants, and
      isoniazid remain common causes of drug induced seizures, bupropion, tramadol, and
      venlafaxine have emerged as common causes of drug-induced seizures for which
      poison center consultation is requested.

PMID- 18072154
TI  - The epidemiology of intentional non-fatal self-harm poisoning in the United
      States: 2001-2004.
AB  - INTRODUCTION: Suicide attempts through intentional poisoning are an important
      public health concern. This investigation sought to determine the different US
      incident rates of poisonings (with intent to do self-harm) by race, sex, and
      gender. METHODS: We used data from the National Electronic Injury Surveillance
      System--All Injury Program (NEISS-AIP) to describe differences in incidence rates
      of non-fatal, self-harm poisonings evaluated in US emergency departments (ED)
      from 2001 to 2004. WISQARS defines self-harm as "either confirmed or suspected
      from injury or poisoning resulting from a deliberate act inflicted on oneself
      with the intent to take one's own life or harm oneself." RESULTS: From 2001 to
      2004, there were 976,974 (95% Confidence Interval (CI) 772,884 - 1,181,065) non
      fatal self-harm poisonings reported in US Emergency Departments. Young white
      females between 15 to 19 years of age were at highest risk with an incidence rate
      of 248 per 100,000 (95% CI 180 - 315). Females had higher rates of self-harm
      poisonings than males: the rate for females was 101 per 100,000 (95% CI 81 -
      123); the rate for males was 66 per 100,000 (95% CI 51 - 81), p < 0.001. Whites
      had slightly higher rates than blacks, and significantly higher rates than
      Hispanics: whites rates were 71 per 100,000 (95% 51 - 91); black rates were 65
      per 100,000 (95% CI 35 - 96), and Hispanic rates were 23 per 100,000 (95% 10 -
      37). There was a significant increase in the incidence rate from 2002 to 2003 (p
      < 0.001). Incident rates decreased for females and males older than 19 years of
      age (p < 0.001 for males and females). CONCLUSION: Recently, the incidence of
      self-harm poisoning has risen considerably. It rose from 75 (CI 53-98) per
      100,000 in 2002 to 94 (CI 74-115) per 100,000 in 2003; incidence remained
      relatively steady in 2004. Whites have higher incidence rates than blacks and
      significantly higher incidence rates than Hispanics. Females are at higher risk
      than males, and adolescent white females are at highest risk. An understanding of
      the demographic factors associated with self-harm poisoning may provide useful
      information to improve prevention and treatment strategies.

PMID- 18072155
TI  - Electrometric measurement of plasma, erythrocyte, and whole blood cholinesterase
      activities in healthy human volunteers.
AB  - INTRODUCTION: The measurement of blood cholinesterase activity is a useful tool
      for monitoring exposure to organophosphate and carbamate insecticides. Blood
      cholinesterase activity is measured colorimetrically or electrometrically.
      Recently, a simple and practical electrometric method has been described and
      validated for measuring blood cholinesterase activity in people and animals. The
      purpose of the present report was to use the modified electrometric technique for
      measuring blood (plasma, erythrocyte and whole blood) cholinesterase activities
      in apparently healthy human volunteers in Mosul, Iraq. METHOD: Cholinesterase
      activities in the plasma, erythrocytes, and whole blood of healthy male (n = 72)
      and female (n = 31) volunteers were measured by an electrometric method; the
      method involved the addition of 0.2 ml of blood sample to 3 ml of distilled water
      followed by 3 ml of barbital-phosphate buffer solution (pH 8.1). The pH (pH1) of
      the mixture was measured, and then 0.1 ml of 7.5% of acetylcholine iodide, as a
      substrate, was added. The reaction mixture was incubated at 37 degrees C for 20
      minutes. The pH (pH2) of the reaction mixture was measured after the end of the
      incubation period. Enzyme activity was expressed as DeltapH/20 min = pH1- pH2 -
      (DeltapH of the blank). The blank was without the blood sample. Following in
      vitro inhibition of pseudo cholinesterase by quinidine sulfate, true
      cholinesterase activity was estimated in the plasma of the subjects. After in
      vitro addition of the organophosphate (chlorpyrifos and methidathion, 0.5 and 1
      microM) and carbamate (carbaryl, 5 and 10 microM) insecticides to the reaction
      mixtures, inhibitions of blood cholinesterases were measured. RESULTS: Mean
      reference cholinesterase activities (DeltapH/20 min) in the plasma, erythrocytes,
      and whole blood of male subjects were 0.98, 1.39, and 1.41, respectively. Females
      were 0.85, 1.22, and 1.23, respectively. Ten minutes after in vitro addition of
      quinidine sulfate to inhibit pseudo cholinesterase activity in the plasma, the
      estimated true cholinesterase activities in males and females were 0.08 and 0.07
      DeltapH/20 min, respectively. The percentage of true cholinesterase in the plasma
      of males and females was 8.2. Using the modified electrometric method, various
      percentages of cholinesterase inhibitions in the plasma, erythrocytes, and whole
      blood were detected after in vitro addition of the organophosphate insecticides
      (chlorpyrifos and methidathion) and the carbamate insecticide (carbaryl) to the
      reaction mixtures. CONCLUSIONS: These findings are the first collective report of
      human plasma, erythrocyte, and whole blood cholinesterase activities as
      determined by the modified electrometric method, and they could serve as
      reference points for future studies that involve human exposure to
      anticholinesterase pesticides.

PMID- 18072156
TI  - Case files of the toxikon medical toxicology fellowship in Chicago: the poisoned
      anesthesiologist.

PMID- 18072157
TI  - Captive subjects: pharmaceutical testing and prisoners.

PMID- 18072158
TI  - Washington teleconferencing program.

PMID- 18072159
TI  - Limited efficacy of calcium and magnesium in a porcine model of hydrofluoric acid
      ingestion.
AB  - OBJECTIVE: This investigation evaluated the effectiveness of calcium and
      magnesium in treating oral hydrofluoric acid (HF) poisoning. METHODS: The
      controlled laboratory investigation used anesthetized pigs. Subjects received HF
      via NG tube, titrated to abolish electrocardiographic abnormalities. The
      untreated group received saline infusion. The treatment group received serial
      injections of calcium chloride (CaCl2) and magnesium chloride (MgCl2). A third
      group received oral infusions of Calcium fluoride (CaF2). We measured heart rate,
      QRS interval, pH, bicarbonate, calcium, magnesium, and potassium. The Wilcoxon
      Rank Sum test was used to compare intra- and inter-subject differences. RESULTS:
      Fatality occurred in all pigs receiving HF. Compared to the untreated group,
      trends for the treatment group were toward a larger amount of HF to produce
      fatality (83.1 +/- 17.5 grams vs. 37.7 +/- 16.1 grams, p = 0.08), to cause QRS
      prolongation (72.5 +/- 25.8vs. 33.8 +/- 14.9 grams, p = 0.08), and to lower
      potassium at mortality (4.9 +/- 0.7 vs. 8.7 +/- 2.7 mEq/L, p = 0.08). No major
      changes in calcium (-1.0 +/- 0.7 mEq/L) or magnesium (0.4 +/- 0.6 mEq/L) occurred
      in the untreated group. Tachycardia developed in all pigs and ventricular
      arrhythmias occurred in 2 of 3 pigs of both groups [CaF2 administration caused no
      QRS prolongation or ventricular arrhythmias and had no effect on laboratory
      parameters]. CONCLUSION: CaCl2 and MgCl2 replacement delayed but did not prevent
      fatality and QRS prolongation. Although this result suggests Ca++ and Mg++ may be
      beneficial in the treatment of systemic HF toxicity, factors other than
      hypocalcemia and hypomagnesemia play a role in toxicity.

PMID- 18072160
TI  - A report of two deaths from massive ibuprofen ingestion.
AB  - INTRODUCTION: Ibuprofen is a commonly used non-steroidal anti-inflammatory drug.
      While the vast majority of exposures to the drug do not result in significant
      morbidity, we are reporting 2 fatalities that resulted from massive ibuprofen
      ingestion. CASE 1: A 17-year-old girl presented to the emergency department (ED)
      following an ibuprofen overdose; she was unresponsive with a metabolic acidosis
      and hypothermic. Her serum ibuprofen concentration was 352 microg/mL: the
      therapeutic range is 10-50 microg/mL. Despite intensive supportive care and
      continuous veno-venous hemofiltration, she expired. CASE 2: A 49-year-old man
      presents to the ED with a history of divalproex sodium and ibuprofen ingestion.
      He was unresponsive, hypotensive, and had a significant metabolic acidosis. His
      serum ibuprofen concentration was 260 microg/mL and serum valproate concentration
      was 560 microg/mL: the therapeutic range is 50-100 microg/mL. In spite of
      supportive care and hemodialysis, he expired. DISCUSSION: We will describe 2
      cases of ibuprofen overdose characterized by cardiovascular collapse, acidosis,
      and hypothermia despite the use of vasopressors and renal replacement therapy.
      Although rarely reported, massive ibuprofen overdose may result in refractory
      multisystem organ failure and death.

PMID- 18072162
TI  - Lithium toxicity from an Internet dietary supplement.
AB  - INTRODUCTION: The widespread availability of medications and herbal products on
      the Internet has increased the potential for poisonings. We are reporting a case
      of mild, acute lithium toxicity occurring after the intentional misuse of a
      lithium-containing "dietary supplement" (Find Serenity Now) obtained over the
      Internet. CASE REPORT: An 18-year-old woman presented to our emergency department
      (ED) after ingesting 18 tablets of Find Serenity Now; each tablet contained,
      according to the listing, 120 mg of lithium orotate [3.83 mg of elemental lithium
      per 100 mg of (organic) lithium orotate compared to 18.8 mg of elemental lithium
      per 100 mg of (inorganic) lithium carbonate]. The patient complained of nausea
      and reported one episode of emesis. Her examination revealed normal vital signs.
      The only finding was a mild tremor without rigidity. Almost 90 minutes after the
      ingestion, her serum lithium level was 0.31 mEq/L, a urine drug screen was
      negative, and an electrocardiogram (ECG) showed a normal sinus rhythm. The
      patient received intravenous fluids and an anti-emetic; one hour later, her
      repeat serum lithium level was 0.40 mEq/L. After 3 hours of observation, nausea
      and tremor were resolved, and she was subsequently transferred to a psychiatric
      hospital for further care. Prior human and animal data have shown similar
      pharmacokinetics and shared clinical effects of these lithium salts. DISCUSSION:
      Over-the-Internet dietary supplements may contain ingredients capable of causing
      toxicity in overdose. Chronic lithium toxicity from ingestion of this product is
      also of theoretical concern.

PMID- 18072161
TI  - Acute clenbuterol overdose resulting in supraventricular tachycardia and atrial
      fibrillation.
AB  - OBJECTIVE: We are presenting a case illustrating the complex metabolic and rhythm
      disturbances associated with acute clenbuterol intoxication. BACKGROUND:
      Clenbuterol is a long-acting beta2-adrenergic agonist primarily used in
      veterinary medicine in the United States. It has become a common drug of abuse by
      body builders because of its reported anabolic and lipolytic properties. In this
      case report, a body builder using veterinary clenbuterol developed significant
      electrolyte and cardiac manifestations. CASE REPORT: A 31-year-old man presented
      to the emergency department approximately 30 minutes after ingesting 1.5 ml (a
      tenfold dosing error) of Ventipulmin syrup (72.5 mcg/ml clenbuterol HCl). The
      product was brought to the emergency department (ED) by the patient. He reported
      no current use of anabolic steroids. He presented in an anxious state with
      complaints of palpitations and shortness of breath. Vital signs upon examination
      were as follows: BP, 122/77 mmHg (16.3/10.3 kPa); HR 254 bpm; RR, 22 bpm;
      Temperature, 97.1 degrees F (36 degrees C); and oxygen saturation, 100% on
      ambient air. His electrocardiogram (ECG) demonstrated supraventricular
      tachycardia with a ventricular rate of 254 bpm. Esmolol was recommended for rate
      control after the unsuccessful use of adenosine and diltiazem. Laboratory studies
      showed potassium, 2.1 mmol/L; magnesium, 1.3 mg/dL (0.54 mmol/L); phosphorus, 1.0
      mg/dL (0.32 mmol/L); serum glucose, 209 mg/dL (11.6 mmol/L); creatinine, 0.8
      mg/dL (70.7 micromol/L); AST, 20 U/L; ALT, 55 U/L; hemoglobin, 12.6 g/dL (126
      g/L); CPK total, 87 U/L; and troponin I, 0.23 mug/L. The patient's urine was
      negative for any drugs of abuse. Clenbuterol levels were not obtained. A second
      ECG, 16 hours post ingestion, reflected atrial fibrillation with a ventricular
      rate of 125 to 147 bpm. On hospital day 3, he was electively cardioverted to
      sinus rhythm; heart rate and rhythm returned to normal, and he was discharged
      with oral metoprolol. DISCUSSION: Clenbuterol is approved for use in countries
      outside the U.S. as a bronchodilator for the treatment of acute asthma
      exacerbations in humans. Although clenbuterol is not a steroid hormone, it
      possesses anabolic properties that increase muscle mass. Its longer duration of
      action compared to other beta2-agonists (such as albuterol) make it a desired
      agent for body-building because of its high and prolonged serum level. The
      mechanism for the short and long-term cardiovascular complications of clenbuterol
      is complex. The anabolic effects of clenbuterol are associated with its beta2
      adrenoreceptor agonist activity on striated skeletal muscles. In addition,
      clenbuterol promotes lipolysis through adipocyte beta3-adrenoreceptors.
      CONCLUSION: Considering the significant number of body-building enthusiasts,
      physicians will continue to encounter clenbuterol abuse in their clinical
      practices.

PMID- 18072163
TI  - The clinical significance of variations in ethanol toxicokinetics.
AB  - INTRODUCTION: Many variables affect the interpretation of an isolated ethanol
      level in an acutely intoxicated patient. This review demonstrates the significant
      variability in metabolism and elimination of ethanol, how it can differ between
      individuals, and the clinical importance of these variables. DISCUSSION: Isolated
      ethanol values in a clinical scenario are only a snapshot of a dynamic process.
      The individual pharmacokinetic differences of people make it extremely difficult
      to estimate ethanol elimination rates or calculate previous ethanol
      concentrations at the time of an accident because of medical-legal reasons. Not
      only are the techniques used in measuring ethanol concentrations in bodily fluids
      (blood, serum, breath, and urine) not equivalent, but also the units used to
      report ethanol concentrations are often misinterpreted. Acute and chronic
      tolerance and social adaptive changes make interpreting this isolated ethanol
      level extremely difficult. The purpose of this review is to enable the clinician
      to appropriately interpret ethanol concentrations. CONCLUSION: The clinical
      evaluation of a patient's inebriation is always more reliable than an isolated
      ethanol level for determining disposition. Only an estimation of a current serum
      ethanol level can be made if the blood draw was performed hours earlier. This
      review is clinically important because it shows the clinically significant
      variability in metabolism and elimination of ethanol and how it can differ
      between individuals. It will also describe different ways to measure ethanol
      concentrations and how to compare them. Finally, the interpretation of isolated
      ethanol levels will be discussed.

PMID- 18072165
TI  - Polonium 210, exposed.

PMID- 18072166
TI  - A review of the review process.

PMID- 18072164
TI  - Case files of the University of Cincinnati fellowship in medical toxicology: two
      patients with acute lethal occupational exposure to hydrogen sulfide.

PMID- 18072167
TI  - Effect of oral administration of aqueous whole extract of cassytha filiformis on
      haematograms and plasma biochemical parameters in rats.
AB  - INTRODUCTION: We evaluated the sub-chronic toxicity of the aqueous herbal extract
      prepared from Cassytha filiformis and administered daily for 28 days at dose
      levels (250, 500, and 1000 mg/kg bw) in male wistar albino rats. The LD50 of the
      aqueous extract was determined. METHODS: The effects on body weights, organ
      weights, and certain haematological and plasma biochemical parameters were
      measured as indices of organ toxicity. RESULTS: The aqueous extract did not
      affect plasma glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate
      transaminase (GPT); however, a significant reduction in alkaline phosphatase
      (ALP) level occurred in all the treated groups. It also did not affect the
      electrolytes (Na , Cl and K ), total and direct bilirubin, creatinine, and
      glucose level. The aqueous extract elicited hypercholesterolaemic effects, but it
      did not affect the Hb, WBC, RBC, PVC, platelets, MCH, MCHC, MCV levels and
      differential counts (lympocytes, neutrophils, monocytes, eosinophils and
      basophils). It also reduced the body weight gain and absolute weight of the
      kidneys. The relative weights of the heart and lungs in some animal groups were
      equally reduced. The acute toxicological evaluation of the plant extract revealed
      an oral LD50 value greater than 500 mg/kg bw. CONCLUSION: This study suggests
      that aqueous extract of C. filiformis administered at normal therapeutic doses is
      not likely to produce severe toxic effects on some organs or haematological and
      biochemical indices in rats.

PMID- 18072168
TI  - Antiemetic use in acetaminophen poisoning: how does the route of N-acetylcysteine
      administration affect utilization?
AB  - INTRODUCTION: We sought to compare antiemetic use after acetaminophen poisoning
      in patients treated with oral or intravenous (IV) N-acetylcysteine (NAC).
      METHODS: Our retrospective chart review identified 20 orally treated patients and
      17 IV-treated patients. For both groups, we calculated the total number of
      antiemetic doses given, their associated cost, and also determined parameters
      that correlated with antiemetic use. RESULTS: IV-treated patients received fewer
      total antiemetic doses than those receiving oral NAC (1.1 0.2 vs. 2.8 0.7; P
      0.04). Antiemetic cost correlated with doses received for both groups; however,
      because the regression lines differed (P 0.02), antiemetic therapy cost was less
      in IV-treated patients. In addition, serum acetaminophen concentration correlated
      with total antiemetic doses in oral NAC patients (P 0.002) but not with IV
      treatment patients (P 0.78). CONCLUSIONS: Intravenous NAC reduced antiemetic
      utilization, and it costs less than oral therapy. Furthermore, antiemetic use
      appeared to be determined by a combination of acetaminophen concentration and NAC
      administration route.

PMID- 18072169
TI  - Valsartan ingestions among adults reported to Texas poison control centers, 2000
      to 2005.
AB  - INTRODUCTION: Little data exist on potentially adverse valsartan ingestions
      reported to poison control centers. METHODS: Using adult ingestions of valsartan
      reported to Texas poison control centers during 2000-2005, I determined the
      proportion of cases involving serious outcomes for selected variables and
      evaluated for statistical significance by calculating the rate ratio (RR) and 95%
      confidence interval (CI). RESULTS: Thirteen (7%) of 185 total cases involved
      serious outcomes. Serious outcomes were significantly more likely to occur with a
      maximum dose 320 mg (RR 9.06, CI 1.30-100.14) or 4 tablets (RR 9.00, CI 2.07
      39.11) or where the circumstances of the exposures involved self-harm or
      malicious intent (RR 17.28, CI 4.98-67.13). CONCLUSIONS: The severity of the
      medical outcome associated with adult valsartan ingestions depended on the dose
      and the circumstances of the ingestion. Such information is useful for creating
      triage guidelines for the management of adult valsartan ingestions.

PMID- 18072170
TI  - Epidemiology of snakebites based on field survey in Chitwan and Nawalparasi
      districts, Nepal.
AB  - INTRODUCTION: Snake envenomation is a major public health issue in the rural
      tropics, but there is no accurate figure of incidence of snakebite. Few studies
      have looked at the epidemiology of venomous snakebite in Nepal. METHODS: Using
      data collection sheets, enumerators randomly sampled, visited, and interrogated
      20% of the population from each district. RESULTS: Of the 2,186 snakebite cases
      studied in two districts from April to September 2005, 66% were from Nawalparasi
      and 34% from Chitwan. 54% were males. 56% of patients consulted traditional
      healers. Most bites occurred in those 10-20 years of age and in those engaged in
      outdoor and agricultural (farmers) activities, but I should note that 15%
      occurred during sleep. Extremity bites accounted for 94%, with 66% in the lower
      extremities and 28% in the upper extremities. Of the total cases, 58% were
      nonenvenomations and 42% were envenomations. Of the total venomous cases, 27%
      died; which is 12% of the total snakebites (2,186). The majority of bites
      occurred in the summer. CONCLUSIONS: This epidemiological study vividly depicted
      the health hazards of snakebites in two areas of rural Nepal.

PMID- 18072171
TI  - Death temporally related to the use of a Beta adrenergic receptor antagonist in
      cocaine associated myocardial infarction.
AB  - INTRODUCTION: Although it is commonly stated that the use of beta adrenergic
      receptor antagonists is contraindicated in patients with cocaine toxicity, actual
      clinical evidence of harm is lacking. This case helps to highlight the risks of
      beta adrenergic receptor antagonists in patients with chest pain associated with
      cocaine use. CASE REPORT: A 54-year-old man was brought to the emergency
      department (ED) complaining of chest pain after using approximately 1 gram of
      intranasal cocaine. Aspirin and nitroglycerin spray relieved his pain. Although
      he remained pain free, tachycardia persisted despite 15 mg of diazepam
      intravenously. Nearly two hours after presentation, a total of 5 mg of metoprolol
      was given for persistent tachycardia (115/minute) and an elevated troponin.
      Shortly thereafter, the patient complained of crushing substernal chest pain,
      developed pulseless electrical activity, and could not be resuscitated.
      DISCUSSION: The administration of beta adrenergic receptor antagonists
      exacerbates cocaine-induced lethality in animals. In humans given smaller doses
      of cocaine, beta adrenergic receptor antagonists exacerbate coronary
      vasoconstriction. Both effects are presumed to occur through unopposed alpha
      adrenergic receptor agonism. Despite these data, actual cases describing adverse
      effects in cocaine users given beta adrenergic receptor antagonists are uncommon.
      This case supports the potential lethality of a cocaine-beta adrenergic receptor
      antagonist interaction.

PMID- 18072172
TI  - Successful outcome after intravenous gasoline injection.
AB  - INTRODUCTION: Gasoline, ingested intentionally or accidentally, is toxic. The
      majority of reported cases of gasoline intoxication involve oral ingestion or
      inhalation. Data are scarce on complications and outcomes following hydrocarbon
      poisoning by intravenous injection. CASE REPORT: Following a suicide attempt by
      intravenous self-injection of 10 ml of gasoline, a 26-year-old medical student
      was admitted to the intensive care unit (ICU) with hemoptysis, symptoms of acute
      respiratory failure, chest pain, and severe abdominal cramps. Gas exchange was
      severely impaired and a chest x-ray indicated chemical pneumonitis. Initial
      treatment consisted of mechanical ventilation, supportive hyperventilation,
      administration of nitrogen oxide (NO), and prednisone. Unfortunately, the patient
      developed multi-organ dysfunction syndrome (MODS) complicated by life-threatening
      severe vasoplegia within 24 hours after gasoline injection. High doses of
      vasopressors along with massive amounts of parenteral fluids were necessary.
      Despite fluid replacement, renal function worsened and required hemofiltration on
      5 sequential days. After 12 days of intensive care management, the patient
      recovered completely and was discharged to a psychiatric care facility.
      DISCUSSION: Intravenous gasoline injection causes major injury to the lungs, the
      organ bearing the first capillary bed encountered. Treatment of gasoline
      poisoning is symptomatic because no specific antidote is available. Early and
      aggressive supportive care may be conducive to a favorable outcome with minimal
      residual pulmonary sequelae.

PMID- 18072173
TI  - QT prolongation and Torsades de Pointes following overdose of ziprasidone and
      amantadine.

PMID- 18072174
TI  - Fetal poisoning after maternal paraquat ingestion during third trimester of
      pregnancy: case report and literature review.
AB  - INTRODUCTION: Paraquat remains one of the common substances involved in
      intentional ingestions in Thailand. However, data on outcomes of paraquat
      ingestion during pregnancy is rarely available and the management is
      controversial. CASE REPORT: A 17-year-old female in 36 weeks of gestation
      attempted suicide by ingesting 1/2 a glass of Gramozonetrade mark (paraquat 27.6
      % w/v) 5 hours prior to arrival to the hospital. Gastric aspiration and lavage
      was performed and she was given 50 g of activated charcoal and 150 g of Fuller's
      Earth suspension. A male infant, weighing 2,390 g with an Apgar score of 71 1010,
      was delivered via emergency caesarean section 7 hours after ingestion. Due to
      presence of paraquat in the gastric lavage fluid, the mother was placed on
      dexamethasone/cyclophosphamide therapy. She developed mild renal insufficiency 63
      hours after the ingestion. The infant developed tachypnea immediately after birth
      that self-resolved. The infant developed tachypnea again on day 6 of life. A
      chest x-ray revealed right lower lobe infiltration that progressed to diffuse
      interstitial pattern; subsequent chest x-rays showed evidence of fibrosis. Both
      mother and infant survived and the infant was discharged and sent home with
      oxygen 0.5 LPM. Upon follow up at 10 months of age, he still had evidence of
      chronic lung disease clinically and on chest x-ray. CONCLUSION: Paraquat
      ingestion during the third trimester of pregnancy usually carries a very poor
      prognosis. Review of reported literature suggests that this case report
      represents only the second survival of mother and child.

PMID- 18072175
TI  - Reversible cardiomyopathy complicating intrathecal baclofen withdrawal: a case
      report.
AB  - This case report is about reversible cardiomyopathy associated with intrathecal
      baclofen withdrawal. Previous literature has reported that enteral baclofen does
      not adequately control intrathecal baclofen withdrawal. In our case, coronary
      atherosclerosis did not play a role in the development of the cardiomyopathy.
      However, reinstitution of intrathecal baclofen promptly resulted in improvement.
      One could hypothesize that myocardial stunning from sympathetic hyperactivity led
      to a similar cardiomyopathy reported with catecholamine excess or acute
      sympathomimetic poisoning.

PMID- 18072176
TI  - Case files of the Drexel University Medical Toxicology Fellowship: methadone
      induced QTc prolongation.

PMID- 18072177
TI  - The implementation of a fast and accurate QM/MM potential method in Amber.
AB  - Version 9 of the Amber simulation programs includes a new semi-empirical hybrid
      QM/MM functionality. This includes support for implicit solvent (generalized
      Born) and for periodic explicit solvent simulations using a newly developed QM/MM
      implementation of the particle mesh Ewald (PME) method. The code provides
      sufficiently accurate gradients to run constant energy QM/MM MD simulations for
      many nanoseconds. The link atom approach used for treating the QM/MM boundary
      shows improved performance, and the user interface has been rewritten to bring
      the format into line with classical MD simulations. Support is provided for the
      PM3, PDDG/PM3, PM3CARB1, AM1, MNDO, and PDDG/MNDO semi-empirical Hamiltonians as
      well as the self-consistent charge density functional tight binding (SCC-DFTB)
      method. Performance has been improved to the point where using QM/MM, for a QM
      system of 71 atoms within an explicitly solvated protein using periodic
      boundaries and PME requires less than twice the cpu time of the corresponding
      classical simulation.

PMID- 18072178
TI  - Carbon nanotube, graphene, nanowire, and molecule-based electron and spin
      transport phenomena using the nonequilibrium Green's function method at the level
      of first principles theory.
AB  - Based on density functional theory, we have developed a program code to
      investigate the electron transport characteristics for a variety of nanometer
      scaled devices in the presence of an external bias voltage. We employed basis
      sets comprised of linear combinations of numerical type atomic orbitals,
      particularly focusing on k-point sampling for the realistic modeling of the bulk
      electrode. The scheme coupled with the matrix version of the nonequilibrium
      Green's function method enables calculation of the transmission coefficients at a
      given energy and voltage in a self-consistent manner as well as the corresponding
      current-voltage (I-V) characteristics. This scheme has advantages because it is
      applicable to large systems, easily transportable to different types of quantum
      chemistry packages, and extendable to time-dependent phenomena or inelastic
      scatterings. It has been applied to diverse types of practical electronic devices
      such as carbon nanotubes, graphene nanoribbons, metallic nanowires, and molecular
      electronic devices. The quantum conductance phenomena for systems involving
      quantum point contacts and I-V curves for a single molecule in contact with metal
      electrodes using the k-point sampling method are described.

PMID- 18072179
TI  - Reactive force fields for proton transfer dynamics.
AB  - A force field-inspired method based on fitted, high-quality multidimensional
      potential energy surfaces to follow proton transfer (PT) reactions in molecular
      dynamics simulations is presented. In molecular mechanics with proton transfer
      (MMPT) a system is partitioned into a region where proton transfer takes place
      and the remaining degrees of freedom which are treated with a conventional force
      field. The implementation of the method and applications to specific chemically
      and biologically relevant scenarios are presented. MMPT is developed in view of
      two primary areas in mind: to follow the molecular dynamics of proton transfer in
      the condensed phase on realistic time scales and to adapt the shape (morphing) of
      the potential energy surface for specific applications. MMPT is applied to PT in
      protonated ammonia dimer, double proton transfer in 2-pyridone-2-hydroxypyridine,
      and the first step of PT from a protein side-chain towards a buried [3Fe4S]
      cluster in ferredoxin I. Specific findings of the work include the fundamental
      role of the N-N vibration as the gating mode for PT in NH4+...NH3 and the
      qualitative understanding of PT from the protein to a metastable active-site
      water molecule in Ferredoxin I.

PMID- 18072180
TI  - Morphology and phase separation of hydrophobic clusters of soy globular protein
      polymers.
AB  - Protein hydrophobic interaction has been considered the most important factor
      dominating protein folding, aggregation, gelling, self-assembly, adhesion, and
      cohesion properties. In this paper, morphology and phase separation of
      hydrophobic clusters, networks, and aggregates of soy globular protein polymers,
      induced by using a reducing agent (NaHSO3), are studied using microscopic
      instruments. The morphology and phase separation of these hydrophobic clusters
      are sensitive to protein structure and composition, pH, and ionic-strength
      (I(m)). Most of the clusters are in spherical-shape architecture and mainly
      consist of hydrophobic polypeptides. Rod-shape clusters were also observed at
      higher ionic strength, and mainly consist of hydrophilic polypeptides. The ratio
      of hydrophobic/hydrophilic (HB/HL) polypeptides is important to facilitate the
      formation of clusters in an environment with a certain pH value and ionic
      strength. At HB/HL 0.8, uniform spherical clusters were observed and diameters
      ranged from 30 to 70 nm. At HB/HL <0.8, large spherical clusters were formed with
      diameters ranging from 100 to 1,000 nm, and at HB/HL >or=1.8, large hydrophobic
      aggregates formed, and size of aggregates can be up to 2 500 nm. When solid
      content increased from 3% to 38%, at I(m) <or= 0.058 mol x L(-1), pH = 4.8, HB/HL
      ratio <0.8, the networks turned into a continuous substance that has strong
      adhesion to various surfaces; at I(m) >or= 0.115 mol x L(-1), HB/HL ratio
      >or=1.8, the large aggregates became very cohesive and viscoelastic. Clear phase
      separation was observed during curing between hydrophobic and hydrophilic protein
      polymers. Phase-separation degree increased as HB/HL ratio increased.

PMID- 18072181
TI  - Loading and in vitro controlled release of indomethacin using amphiphilic
      cholesteryl-bearing carboxymethylcellulose derivatives.
AB  - Amphiphilic CCMCs were synthesized under mild conditions and their chemical
      structures were characterized by FT-IR and 1H NMR spectroscopy. Fluorescence
      analysis showed that CCMCs could self-associate to form polymeric micelles in
      aqueous solution. IND was encapsulated during the formation of CCMC micelles and
      its in vitro release properties were investigated. The loading capacity was more
      than 50% and the loaded IND was slowly and steadily released into the medium over
      a period of 8 h. The CCMC micelles showed pH-responsive behavior during the drug
      loading and release processes. CCMC is promising as a potential delivery system
      for the controlled release of IND with a pH-responsive property.

PMID- 18072182
TI  - Composite nano-titanium oxide-chitosan artificial skin exhibits strong wound
      healing effect-an approach with anti-inflammatory and bactericidal kinetics.
AB  - A composite nano-TiO2-chitosan with collagen artificial skin (NTCAS) showed
      promising characteristics of moderate water absorptivity (110 wt.-%), fine
      thickness (0.34 mm), low density (0.33 mg x mm(-3)), moderate biodegradability
      (<3.0%), and favorable time-dependent biodegradability (0.0521 mg x mL(-1) x h(
      1) on Day 0; 0.0006 mg x mL(-1) x h(-1)on Day 3 post covering). More importantly,
      it showed uniquely potent bactericidal (sterilization) property with relatively
      large values of pseudo first-order kinetic coefficients (0.1736-0.0360 min(-1))
      for TiO2 contents ranging from 2.63 x 10(-5) to 2.11 x 10(-4) mg x cm(-2). In
      wounded subjects, NTCAS showed a steady level of TNF-alpha, while the IL-6 level
      reached a peak on Day 7, although significantly lower than in the control and
      Duoderm groups. In the animal model, NTCAS showed better and faster recovery than
      the other groups, which can be attributed to the unique bactericidal effect of
      nano-TiO2 and immune-enhancing effect of chitosan. NTCAS is a promising
      artificial skin substitute and is superior to any other market product currently
      in use.

PMID- 18072183
TI  - PAM-microfabricated polyurethane scaffolds: in vivo and in vitro preliminary
      studies.
AB  - Polymeric scaffolds were realised with linear degradable PU in the form of
      square, hexagonal and octagonal grids. They were characterised in terms of their
      mechanical properties. Analysis shows that the mechanical properties of the
      scaffolds depend on their geometries which are easily modulated using PAM. In
      vitro biological assays showed that PU promotes the adhesion and proliferation of
      fibroblast cells and that cell activities are better on PU scaffolds than on PU
      films. In vivo implantation of PU and PLGA scaffolds and PU films demonstrated
      that the scaffolds are completely resorbed after three months with a slight
      inflammatory response, while the PU film was still present after six months with
      an intense granulomatous reaction.

PMID- 18072184
TI  - Assembly of the inner kinetochore proteins CENP-A and CENP-B in living human
      cells.
AB  - DNA segregation in mammalian cells during mitosis is an essential cellular
      process that is mediated by a specific subchromosomal protein complex, the
      kinetochore. Malfunction of this complex results in aneuploidy and can cause
      cancer. A subkinetochore complex, the "inner kinetochore", is present at the
      centromere during the entire cell cycle. Its location seems to be defined by the
      settlement of CENP-A (CENH3), which replaces histone H3 in centromeric
      nucleosomes. This suggests that CENP-A can recruit further inner kinetochore
      proteins by direct binding. Surprisingly, intense in vitro studies could not
      identify an interaction of CENP-A with any other inner kinetochore protein.
      Instead, centromere identity seems to be maintained by a unique nucleosome, which
      might have a modified structure or epigenetic state that serves to distinguish
      the centromere from the rest of the chromosome. We investigated the association
      of CENP-A and CENP-B by fluorescence intensity and lifetime-based FRET
      measurements in living human HEp-2 cells. We observed Forster resonance energy
      transfer (FRET) between CENP-A and CENP-B at centromere locations; this indicates
      that these proteins are in the molecular vicinity (<10 nm) of each other. In
      addition, we analysed protein-protein interactions within the centromeric
      nucleosome. We could detect energy transfer between CENP-A and histone H4 as well
      as between CENP-A molecules themselves. On the other hand, no FRET was detected
      between CENP-A and H2A.1 or H3.1. Our data support the view that two CENP-A
      molecules are packed with H4, but not with H3, in a single centromeric
      nucleosome.

PMID- 18072185
TI  - Quenching of fluorescent nucleobases by neighboring DNA: the "insulator" concept.
AB  - Fluorescent nucleosides are widely used as probes of biomolecular structure and
      mechanism in the context of DNA, but they often exhibit low quantum yields
      because of quenching by neighboring DNA bases. Here we characterize the quenching
      by DNA of fluorescent nucleosides that have pyrene (Y), perylene (E), benzopyrene
      (B), or 2-aminopurine (2AP) as nucleobase replacements, and we investigate the
      effect of inserting varied nucleosides as potential "insulators" between the
      fluorescent nucleosides and other nearby DNA bases as a strategy for increasing
      quantum yields. The data show that the hydrocarbons are quenched by adjacent
      pyrimidines, with thymine being the strongest quencher. The quantum yield of
      pyrene is quenched 120-fold by a single adjacent T, that of benzopyrene tenfold,
      and that of perylene by a factor of 2.5. Quenching of excimer and exciplex
      dinucleoside labels (Y-Y, Y-E, E-E, etc.) was considerably lessened, but was
      strongest with neighboring thymine. 2-Aminopurine (2AP) is most strongly quenched
      (15-fold) by neighboring G. We tested four different insulator candidates for
      reducing this quenching by measuring the fluorescence of short oligonucleotides
      containing insulators placed between a fluorescent base and a quenching base. The
      insulators tested were a C(3) abasic spacer (S), dihydrothymidine nucleoside
      (DHT), terphenyl nucleoside (TP), and adenine deoxynucleoside (dA). Results
      showed that the abasic spacer had little effect on quenching, while the other
      three had substantial effects. DHT and terphenyl enhanced fluorescence of the
      fluorophores by factors of 5 to 70. Adenine base reduced the quenching of pyrene
      40-fold. The results underscore the importance of the nearest neighbors in DNA
      quenching mechanisms, and establish simple strategies for enhancing fluorescence
      in labeled DNAs.

PMID- 18072186
TI  - Conformational analysis of a dermatan sulfate-derived tetrasaccharide by NMR,
      molecular modeling, and residual dipolar couplings.
AB  - The solution conformation behavior of a dermatan-derived tetrasaccharide--Delta
      HexA-(1-->3)-GalNAc4S-beta-(1-->4)-IdoA-alpha-(1-->3)-red-GalNAc4S (S is a
      sulfate group)--has been explored by means of NMR spectroscopy, especially by NOE
      based conformational analysis. The tetrasaccharide was present as four species,
      two of which are chemically different in the anomeric orientation of the reducing
      2-deoxy-2-acetamido-galactose (red-GalNAc) residue, while the other two are the
      result of different conformations of the iduronic acid (IdoA) unit. The two alpha
      beta-interconverting anomers were present in a 0.6:1 ratio. Ring conformations
      have been defined by analysis of (3)J(H,H) coupling constants and interresidual
      NOE contacts. Both 2-deoxy-2-acetamido-galactose (GalNAc) residues were found in
      the (4)C(1) chair conformation, the unsaturated uronic acid (Delta-Hex A) adopts
      a strongly predominant half-chair (1)H(2) conformation, while the IdoA residue
      exists either in the (1)C(4) chair or in the (2)S(0) skewed boat geometries, in a
      4:1 ratio. There is a moderate flexibility of Phi and Psi torsions as suggested
      by nuclear Overhauser effects (NOEs), molecular modeling (MM), and molecular
      dynamics (MD) studies. This was further investigated by residual dipolar
      couplings (RDCs). One-bond C--H RDCs ((1)D(C,H)) and long-range H-H ((3)D(H,H))
      RDCs were measured for the tetrasaccharide in a phage solution and interpreted in
      combination with restrained MD simulation. The RDC-derived data substantially
      confirmed the validity of the conformer distribution resulting from the NOE
      derived simulations, but allowed an improved definition of the conformational
      behavior of the oligosaccharides in solution. In summary, the data show a
      moderate flexibility of the four tetrasaccharide species at the central
      glycosidic linkage. Differences in the shapes of species with the IdoA in skew
      and in chair conformations and in the distribution of the sulfate groups have
      also been highlighted.

PMID- 18072187
TI  - The structure of the plutonium oxide nanocluster [Pu38O56Cl54(H2O)8]14-.

PMID- 18072188
TI  - Examination of the mixed-valence state of the doubly boron-bridged diferrocene
      cation [(FeCp)2{mu-C10H6(BPh)2}]+.
AB  - A series of mixed-valent (MV) complexes [(FeCp)2(mu-C10H6(BPh)2)]+X ([1+]X; X=I
      5, PF6, SbF6, B(C6F5)4) were prepared by oxidation of diboradiferrocene
      [(FeCp)2(mu-C10H6(BPh)2)] (1) with I 2, AgPF6, and AgSbF6, respectively, and
      through anion exchange of the I 5(-) salt with [Li(Et2O)x][B(C6F5)4] in the case
      of X=B(C6F5)4. The MV state of the cation was investigated in solution by
      multinuclear NMR spectroscopy, CV, and UV/Vis-NIR absorption spectroscopy, and in
      the solid state by IR spectroscopy, single-crystal X-ray crystallography, and
      Mossbauer spectroscopy. The cyclic voltammogram of 1 shows two distinct redox
      waves with a large redox splitting of Delta E=510 mV in CH2Cl2 and the NIR
      spectrum for the mono-oxidized species displays an intervalence charge-transfer
      band at around 1500 to 1700 nm depending on the specific counterion present. The
      X-ray crystal structures of [1+]X show inversion-symmetric cations with X=I 5 and
      B(C6F5)4 and unsymmetric valence-trapped structures composed of one ferrocene and
      one ferrocenium moiety with X=PF6 and SbF6. Mossbauer data for X=PF6 are
      consistent with valence trapping at all temperatures between 90 and 343 K. In
      comparison, fast electron transfer is evident on the Mossbauer timescale for X=I
      5 and temperature-dependent behavior is observed for X=B(C6F5)4. The anion
      dependence of the X-ray structural and Mossbauer data is discussed in the context
      of crystal symmetry and the possibility of static and dynamic disorder effects is
      considered.

PMID- 18072189
TI  - Deracemization of secondary alcohols through a concurrent tandem biocatalytic
      oxidation and reduction.

PMID- 18072190
TI  - Thiol-catalyzed stereoselective transfer hydroamination of olefins with N
      aminated dihydropyridines.

PMID- 18072191
TI  - Photobleaching in two-photon scanning fluorescence correlation spectroscopy.
AB  - Two-photon excitation in fluorescence correlation spectroscopy (FCS) is often
      preferred to one-photon excitation because of reduced bulk photobleaching and
      photodamage, and deeper penetration into scattering media, such as thick
      biological specimens. Two-photon FCS, however, suffers from lower signal-to-noise
      ratios which are directly related to the lower molecular brightness achieved. We
      compare standard FCS with a fixed measurement volume with scanning FCS, where the
      measurement volume is scanned along a circular path. The experimental results
      show that photobleaching is the dominant cause of the effects observed at the
      high excitation powers necessary for good signal-to-noise ratios. Theoretical
      calculations assuming a nonuniform excitation intensity profile, and using the
      concept of generalized volume contrast, provide an explanation for the
      photobleaching effects commonly observed in two-photon FCS at high excitation
      intensities, without having to assume optical saturation. Scanning alleviates
      these effects by spreading the photobleaching dose over a larger area, thereby
      reducing the depletion of fluorescent molecules in the measurement volume. These
      results, which facilitate understanding of the photobleaching in FCS and of the
      positive effects of scanning, are particularly important in studies involving the
      autocorrelation amplitude g(0), such as concentration measurements or binding
      studies using fluorescence cross-correlation between two labeled species.

PMID- 18072192
TI  - Rapid screening of anthocyanins in berry samples by surfactant-mediated matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Surfactant-mediated matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS) has been used for the identification of
      flavonoids from three berry extracts: lowbush blueberry (Vaccinium
      angustifolium), lingonberry (Vaccinium vitis-idaea), and blackberry (Rubus
      armeniacus). The addition of the surfactant led to suppression of matrix ions
      from both alpha-cyano-4-hydroxycinnamic acid (CHCA) and 2',4',6'
      trihydroxyacetophenone (THAP). This is the first case of this method being
      successfully employed with a matrix other than CHCA. It was observed that CHCA
      led to a great deal of fragmentation of the sugar moiety from glycosides, whereas
      THAP produced more intact glycoside molecules, and thus leads to better
      characterization of the flavonoids in a berry sample. The flavonoids were
      characterized and quantified by liquid chromatography/electrospray ionization
      mass spectrometry (LC/ESI-MS) with UV detection. Although MALDI-TOF-MS did not
      lead to the identification of as many flavonoids, it did enable us to identify
      many anthocyanin glycosides. Quantification was achieved and demonstrated that
      use of the THAP matrix can enable quantification of the intact glycosides with
      relative standard deviation (RSD) values of less than 10% with surfactant
      addition. These results are comparable with LC results. MALDI-TOF-MS with THAP
      matrix thus provided a rapid method for the qualitative screening of these
      compounds. It took only a few minutes, greatly reducing the analysis time from
      that in traditional LC/MS methods.

PMID- 18072193
TI  - Transient expression of LIM-domain transcription factors is coincident with
      delayed maturation of photoreceptors in the chicken retina.
AB  - In the retina of warm-blooded vertebrates, photoreceptors are specified many days
      before the onset of synaptogenesis and the expression of photopigments. The
      factors that regulate the maturation of photoreceptors in the developing retina
      remain unknown. We report here that photoreceptors transiently express LIM-domain
      transcription factors during the development of the chicken retina. We examined
      the differentiation of photoreceptors through the normal course of embryonic
      development and at the far periphery of the postnatal retina, where the
      differentiation of photoreceptors is slowed and persists across a spatial
      gradient. In the embryonic retina, we find visinin-positive photoreceptors that
      transiently express Islet2 and Lim3 starting at E8 and ending around E15, but
      persisting in far peripheral regions of the retina through the first 2 weeks of
      postnatal development. During early stages of photoreceptor maturation, there is
      coincident and transient expression of the LIM-domain factors with axonin1, a
      cell surface glycoprotein that is a member of the immunoglobulin superfamily.
      Coincident with the downregulation of Islet2 and Lim3, we find the upregulation
      of calbindin, red/green opsin, rhodopsin, and a synaptic marker in the outer
      plexiform layer (OPL; dystrophin). In the periphery of the postnatal retina,
      photoreceptors that express Islet2, Lim3, and axonin1 do not overlap with
      photoreceptors that express calbindin, red/green opsin, rhodopsin, and
      dystrophin. We propose that Islet2 and Lim3 may promote the expression of genes
      that are involved in the early stages of differentiation but may suppress the
      expression of genes that are required in the mature photoreceptors.

PMID- 18072195
TI  - Candidate biomarkers in renal cell carcinoma.
AB  - Although the human genome has been decoded, the knowledge about the pathogenesis
      of diseases including cancer is still limited. By focusing on renal cell
      carcinoma (RCC) we here summarize the data of various research groups analyzing
      the protein/peptide expression profiles of tumor lesions/cell lines or serum
      obtained from patients and respective controls. Different powerful approaches
      such as 2-DE, PROTEOMEX/SERPA/SPEARS, and T cell epitope discovery upon elution
      of MHC class I-bound peptides in combination with MS/LC-MS/MS revealed 500
      differentially expressed proteins. The overlap in target recognition limits the
      pool to 299 unique protein identities, but only few thereof (12%) have been
      validated. The management, analysis, and interpretation of the distinct data sets
      derived from 27 publications required bioinformatic restructuring of the results.
      However, the comprehensive analysis of the results expands the knowledge about
      the pathophysiology of RCC in particular of the most prominent clear cell subtype
      by providing information on the differentially expressed proteins, their
      regulation status in RCC compared to normal kidney epithelium next to additional
      information on MHC-presented T cell epitopes and on serological targets. Despite
      the low number of validated differentially expressed proteins some of them might
      serve as candidate biomarkers for the diagnosis and/or as therapeutic targets.

PMID- 18072194
TI  - Myocardial ischemia/reperfusion causes VDAC phosphorylation which is reduced by
      cardioprotection with a p38 MAP kinase inhibitor.
AB  - Myocardial ischemia (MI) and reperfusion (R) results in activation of the p38 MAP
      kinase pathway. This pathway phosphorylates transcription factors and cytoplasmic
      proteins leading to expression of adhesion molecules and cytokines, increased
      neutrophil activation, and finally, myocardial necrosis and apoptosis. We studied
      the effects of a p38 MAP kinase inhibitor, PD169316, on cardioprotection, protein
      expression, and tyrosine phosphorylation, in a rabbit model of 1 h of (MI) and 3
      h of (R). PD169316 administered just before (R) significantly reduced myocardial
      neutrophil accumulation, necrosis area (28.4 +/- 7.9% vs. 56.4 +/- 7.9%
      necrosis/AAR), and CK release compared to a vehicle treated group (p<0.05). We
      found several proteins altered in expression following MI + R alone or with p38
      inhibition including myofilament proteins, energetics proteins, heat shock
      proteins, and the mitochondrial porin VDAC-1. p38 MAPK inhibition significantly
      reduced the phosphorylation of VDAC-1 which is a known mitochondrial regulator of
      cell survival. Thus, p38 MAP kinase inhibition with PD169316 is cardioprotective,
      reduces neutrophil activation, and controls protein expression and
      phosphorylation in MI and reperfusion.

PMID- 18072201
TI  - Chorea-ballism associated with familial amyotrophic lateral sclerosis. A
      clinical, genetic, and neuropathological study.
AB  - Hyperkinetic movements in amyotrophic lateral sclerosis (ALS) are extremely rare.
      We present clinical, neuropathological, and genetic data for a 53-year-old woman
      with spinal onset ALS presenting chorea affecting the face, mouth, neck, and
      hands, and ballism in both arms 31 months after leg weakness onset. Her father
      and older sister had ALS, but had no movement disorders. As well as the typical
      neuropathological findings of ALS (marked upper and lower motor neuron loss),
      post-mortem examination showed prominent neuronal loss and gliosis in the
      subthalamus, and in the internal globus pallidus, substantia nigra pars compacta,
      and red nucleus. No abnormalities were found in the caudate, putamen, and
      thalamus. No defects were found in the SOD1, HD, and DRPLA genes. These data
      support the idea that choreo-ballism in ALS Plus may be the result of pallido
      luyso-rubro-nigral atrophy, despite not being the result of concomitant DRPLA
      based on neuropathological and genetic criteria.

PMID- 18072203
TI  - Expression of proteins containing disulfide bonds in an insect cell-free system
      and confirmation of their arrangements by MALDI-TOF MS.
AB  - Escherichia coli alkaline phosphatase (AP) and human lysozyme (h-LYZ), which
      contain two and four disulfide bonds, respectively, were expressed in a cell-free
      protein synthesis system constructed from Spodoptera frugiperda 21 (Sf21) cells.
      AP was expressed in a soluble and active form using the insect cell-free system
      under non-reducing conditions, and h-LYZ was expressed in a soluble and active
      form under non-reducing conditions after addition of reduced glutathione (GSH),
      oxidized glutathione (GSSG), and protein disulfide isomerase (PDI). The in vitro
      synthesized proteins were purified by means of a Strep-tag attached to their C
      termini. Approximately 41 microg AP and 30 microg h-LYZ were obtained from 1 mL
      each of the reaction mixture. The efficiency of protein synthesis approached that
      measured under reducing conditions. Analysis of the disulfide bond arrangements
      by MALDI-TOF MS showed that disulfide linkages identical to those observed in the
      wild-type proteins were formed.

PMID- 18072204
TI  - "Glyco-peakfinder"--de novo composition analysis of glycoconjugates.
AB  - Mass spectrometric techniques are the key technology for rapid and reliable
      glycan analysis. However, the lack of robust, dependable, and freely available
      software for the (semi-) automatic annotation of mass spectra is still a severe
      bottleneck that hampers their rapid interpretation. In this article the "Glyco
      Peakfinder" web-service is described allowing de novo determination of glycan
      compositions from their mass signals. Starting from a basic set of mandatory
      masses of glycan components, the calculation can be performed without any
      knowledge concerning the biological background of the sample or the fragmentation
      technique used. "Glyco-Peakfinder" assigns all types of fragment ions including
      monosaccharide cross-ring cleavage products and multiply charged ions. It
      provides full user control to handle modified glycans (persubstituted molecules,
      reducing-end modifications, glycoconjugates) and ion types. The formula applied
      to calculate the fragment masses and an outline of the implemented algorithm are
      discussed. A systematic evaluation of the dependence of all factors influencing
      the computation time revealed strikingly different impact of the individual
      calculation steps. To provide access to known carbohydrate structures a
      "composition search" in the open access database GLYCOSCIENCES.de can be
      performed. The service is available at the URL:
      www.eurocarbdb.org/applications/ms-tools.

PMID- 18072205
TI  - The significance of biochemical and molecular sample integrity in brain
      proteomics and peptidomics: stathmin 2-20 and peptides as sample quality
      indicators.
AB  - Comparisons of transcriptional and translational expression in normal and
      abnormal states are important to reach an understanding of pathogenesis and
      pathophysiology. Maintaining the biochemical, molecular, and structural sample
      integrity is essential for correct sample comparisons. We demonstrate that both
      proteins and neuropeptides, including their PTMs, are subjected to massive
      degradation in the brain already 1 min postmortem. Further, markers for
      determining the integrity and status of a biological sample were identified. The
      protein fragment stathmin 2-20 correlated well with the general level of
      postmortem degradation and may serve as a sample quality indicator for future
      work, both in animal and human postmortem brains. Finally, a novel method for
      preventing degradation of proteins and peptides in postmortem tissue is presented
      using rapid and uniform conductive heat transfer on tissue prior to the actual
      sample preparation procedures, which enables the relatively low-abundant
      neuropeptides to remain intact, minimizes degradation of proteins by proteolysis,
      and conserves the PTMs of the neuropeptides.

PMID- 18072206
TI  - Phosphorylation-regulated cleavage of the reticulon protein Nogo-B by caspase-7
      at a noncanonical recognition site.
AB  - Reticulons (RTNs) are a large family of transmembrane proteins present throughout
      the eukaryotic domain in virtually every cell type. Despite their wide
      distribution, their function is still mostly unknown. RTN4, also termed Nogo,
      comes in three isoforms, Nogo-A, -B, and -C. While Nogo-A has been described as
      potent inhibitor of nerve growth, Nogo-B has been implicated in vascular
      remodeling and regulation of apoptosis. We show here that Nogo-B gets cleaved by
      caspase-7, but not caspase-3, during apoptosis at a caspase nonconsensus site. By
      a combination of MS and site-directed mutagenesis we demonstrate that proteolytic
      processing of Nogo-B is regulated by phosphorylation of Ser(16) within the
      cleavage site. We present cyclin-dependent kinase (Cdk)1 and Cdk2 as kinases that
      phosphorylate Nogo-B at Ser(16) in vitro. In vivo, cleavage of Nogo-B is markedly
      increased in Schwann cells in a lesion model of the rat sciatic nerve. Taken
      together, we identified an RTN protein as one out of a selected number of caspase
      targets during apoptosis and as a novel substrate for Cdk1 and 2. Furthermore,
      our data support a functionality of caspase-7 that is distinct from closely
      related caspase-3.

PMID- 18072207
TI  - Role of group A Streptococcus HtrA in the maturation of SpeB protease.
AB  - The serine protease high-temperature requirement A (HtrA) (DegP) of the human
      pathogen Streptococcus pyogenes (group A Streptococcus; GAS) is localized to the
      ExPortal secretory microdomain and is reportedly essential for the maturation of
      cysteine protease streptococcal pyrogenic exotoxin B (SpeB). Here, we utilize
      HSC5 (M5 serotype) and the in-frame isogenic mutant HSC5DeltahtrA to determine
      whether HtrA contributes to the maturation of other GAS virulence determinants.
      Mutanolysin cell wall extracts and secreted proteins were arrayed by 2-DE and
      identified by MALDI-TOF PMF analysis. HSC5DeltahtrA had elevated levels of cell
      wall-associated M protein, whilst the supernatant had higher concentrations of M
      protein fragments and a reduced amount of mature SpeB protease, compared to wild
      type (WT). Western blot analysis and protease assays revealed a delay in the
      maturation of SpeB in the HSC5DeltahtrA supernatant. HtrA was unable to directly
      process SpeB zymogen (proSpeB) to the active form in vitro. We therefore conclude
      that HtrA plays an indirect role in the maturation of cysteine protease SpeB.

PMID- 18072209
TI  - Proteomic identification of tyrosine nitration targets in kidney of spontaneously
      hypertensive rats.
AB  - Nitrosative and oxidative stress are implicated in the development of
      hypertension. Events in the renal medulla may play a key role in the development
      and progression of hypertension. This may arise through disruption of nitric
      oxide signalling in the medulla and be accompanied by enhanced nitrosative and
      oxidative stress as indicated by the presence of proteins containing 3
      nitrotyrosine. Here we demonstrate enhanced protein nitration in the medulla of
      spontaneously hypertensive rats. We have identified several nitrated proteins
      with both varied subcellular location and functional roles. These proteins are
      involved in nitric oxide signalling, antioxidant defense and energy metabolism.
      Moreover, increased nitration was observed in conjunction with enhanced oxidative
      damage as evidenced by the presence of protein carbonyl oxidative stress
      biomarkers. Our results suggest that kidney medulla is subject to enhanced
      nitrosative and oxidative stress, and that resulting protein modifications may
      contribute to the progression of hypertension.

PMID- 18072208
TI  - The HcaR regulatory protein of Photorhabdus luminescens affects the production of
      proteins involved in oxidative stress and toxemia.
AB  - Comparison of the proteomes of wild-type Photorhabdus luminescens and its hcaR
      derivative, grown in insect hemolymph, showed that hcaR disruption decreased the
      production of toxins (tcdA1, mcf, and pirAB) and proteins involved in oxidative
      stress response (SodA, AhpC, Gor). The disruption of hcaR did not affect growth
      rate in insects, but did delay the virulence of P. luminescens in Bombyx mori and
      Spodoptera littoralis larvae. This delayed virulence was associated with a lower
      toxemia rather than delay in bacteremia. The disruption of hcaR also increased
      bacterial sensitivity to hydrogen peroxide. A sodA mutant and an hcaR mutant had
      similar phenotypes in terms of sensitivity to hydrogen peroxide, virulence, toxin
      gene expression, and growth rate in insects. Thus, the two processes affected by
      hcaR disruption - toxemia and oxidative stress response - appear to be related.
      Besides, expression of toxin genes tcdA1, mcf, and pirAB was decreased by
      paraquat challenge. We provide here the first demonstration of the importance of
      toxemia for P. luminescens virulence. Our results also highlight the power of
      proteomic analysis for detecting unexpected links between different, concomitant
      processes in bacteria.

PMID- 18072212
TI  - Microfluidic platform with mass spectrometry detection for the analysis of
      phosphoproteins.
AB  - The development of novel and reliable technologies for the analysis of proteins
      and their post-translational modifications, in particular, has recently received
      much attention and interest. The implementation of a fully integrated
      microfluidic device interfaced with MS detection for the analysis of
      phosphoproteins is presented in this paper. The microfluidic platform (3''x1.5'')
      comprises two individual sample processing systems: one for performing direct
      sample infusion and one for performing microfluidic LC separations. Various MS
      detection strategies, specific for the study of post-translational modifications,
      were conducted using alpha-casein as a model protein. Neutral loss ion mapping,
      data-dependent triple-play and neutral loss analysis, and in situ
      dephosphorylation followed by LC separation and MS detection were performed.
      Consistent results in identifying phosphopeptides with conventional and
      microfluidic instrumentation have been obtained. Unlike with conventional
      instrumentation, however, the microfluidic device enabled the completion of each
      analysis from only a few microliters of sample, in approximately 10-15 min, and
      on a bioanalytical platform that facilitates multiplexing and disposability, and
      thus high-throughput, contamination-free analysis.

PMID- 18072213
TI  - Detection of single-base mutations using 1-D microfluidic beads array.
AB  - The application of a 1-D microfluidic beads array that is composed of
      individually addressable functionalized SiO2 beads has been demonstrated for
      detection of single-base mutations based on "sandwich" hybridization assay
      without additional sample labeling and PCR amplification. We concentrated on
      detection of mutations in the human p53 tumor suppressor gene with more than 50%
      mutation frequency in the known human cancers. Using a microinjection system,
      functionalized beads could be selectively and linearly arrayed in a single
      microfluidic channel comprising many periodic chambers. This 1-D microfluidic
      beads array was sufficiently sensitive to identify single-nucleotide mutations in
      40 pM quantities of DNA targets and could discriminate the mutated alleles in an
      excess of nonmutated alleles at a level of one mutant in 100 wild-type sequences.
      The surface of beads was regenerated and rehybridized up to six times without
      obvious loss of signal. The entire reaction process was done at room temperature
      within minutes, and only 2-10 microL sample solution was needed to complete the
      whole detection process. The p53 genotypes of A549, CNE2, and SKBr-3 cell lines
      were also correctly evaluated by using mRNA extracts as target without need for
      sample labeling and amplification. Thus, this platform enabled rapid and exact
      discrimination of gene mutations with the advantages of reusability, simple
      handling of liquid, low cost, and little reagent consumption.

PMID- 18072214
TI  - Real-time monitoring of intracellular calcium dynamic mobilization of a single
      cardiomyocyte in a microfluidic chip pertaining to drug discovery.
AB  - A microfluidic method for real-time quantitative measurement of cellular response
      pertaining to drug discovery is reported. This method is capable of multiple-step
      liquid delivery for measuring the drug response of a single cardiomyocyte, due to
      the improved cell retention by a newly designed chip. The chip, which consists of
      a cell-retention chamber with a weir structure, was fabricated just by a one
      photomask microfabrication procedure followed by on-chip etching. This method
      differs from the conventional method, which uses two-mask photolithography to
      fabricate the microchannel (deep etch) and the weir structure (shallow etch). The
      dimensions of the weir structure have been predicted by a mathematical model, and
      confirmed by confocal microscopy. Using this microfluidic method, the dynamic
      [Ca2+]i mobilization in a single cardiomyocyte during its spontaneous contraction
      was quantified. Furthermore, we measured the cellular response of a cardiomyocyte
      on (i) a known cardiotonic agent (caffeine), (ii) a cardiotoxic chemotherapeutic
      drug (daunorubicin), and (iii) an herbal anticancer drug candidate -
      isoliquiritigenin (IQ) based on the fluorescent calcium measurement. It was found
      that IQ had produced a less pronounced effect on calcium mobilization( )of the
      cardiomyocytes whereas caffeine and daunorubicin had much stronger effects on the
      cells. These three experiments on cardiomyocytes pertaining to drug discovery
      were only possible after the improved cell retention provided by the new chip
      design (MV2) required for multiple-step real-time cellular analysis on a
      microchip, as compared with our old chip design (MV1).

PMID- 18072215
TI  - Microfluidic chip-based cell electrophoresis with multipoint laser-induced
      fluorescence detection system.
AB  - In this work, the electrophoretic mobility (EPM) measurement of individual cells
      was investigated by a simple on-chip electrophoresis system with LIF multipoint
      detection. The system enabled the characterization of cell electrophoresis
      behavior as well as the fluorescence signal from individual cells simultaneously.
      The measurement yielded the electropherograms of a large number of cells labeled
      with dye, in which the migration time and migration distance could be obtained
      easily. The EPM has been demonstrated to be different between the K562 cells and
      K562 cells treated with anticancer drug arsenic trioxide (As2O3). The K562 cells
      were found to exhibit a lower EPM compared to the cells after drug addition with
      different concentration. In this preliminary study, over 300 cells could be
      analyzed within 2 h, demonstrated a much higher analysis throughput compared with
      traditional methods. The established system is simple and fast, which is expected
      to be a promising method for evaluating cell surface properties and to be useful
      in clinical and pharmaceutical applications.

PMID- 18072216
TI  - Faster and improved microchip electrophoresis using a capillary bundle.
AB  - Joule heating generated in CE microchips is known to affect temperature gradient,
      electrophoretic mobility, diffusion of analytes, and ultimately the efficiency
      and reproducibility of the separation. One way of reducing the effect of Joule
      heating is to decrease the cross-section area of microchannels. Currently, due to
      the limit of fabrication technique and detection apparatus, the typical
      dimensions of CE microchannels are in the range of 50-200 microm. In this paper,
      we propose a novel approach of performing microchip CE in a bundle of extremely
      narrow channels by using photonic crystal fiber (PCF) as separation column. The
      PCF was simply encapsulated in a poly(methyl methacrylate) (PMMA) microchannel
      right after a T-shaped injector. CE was simultaneously but independently carried
      out in 54 narrow capillaries, each capillary with diameter of 3.7 microm. The
      capillary bundle could sustain high electric field strength up to 1000 V/cm due
      to efficient heat dissipation, thus faster and enhanced separation was attained.

PMID- 18072217
TI  - Further improvement of hydrostatic pressure sample injection for microchip
      electrophoresis.
AB  - Hydrostatic pressure sample injection method is able to minimize the number of
      electrodes needed for a microchip electrophoresis process; however, it neither
      can be applied for electrophoretic DNA sizing, nor can be implemented on the
      widely used single-cross microchip. This paper presents an injector design that
      makes the hydrostatic pressure sample injection method suitable for DNA sizing.
      By introducing an assistant channel into the normal double-cross injector, a
      rugged DNA sample plug suitable for sizing can be successfully formed within the
      cross area during the sample loading. This paper also demonstrates that the
      hydrostatic pressure sample injection can be performed in the single-cross
      microchip by controlling the radial position of the detection point in the
      separation channel. Rhodamine 123 and its derivative as model sample were
      successfully separated.

PMID- 18072220
TI  - Dielectrophoresis for the manipulation of nanobioparticles.
AB  - Dielectrophoresis (DEP) is a nondestructive electrokinetic mechanism with great
      potential for the manipulation of bioparticles. DEP is the movement of particles
      induced by polarization effects in nonuniform electric fields. Since the 1960s,
      this technique has been successfully used for the manipulation of
      microbioparticles, such as microorganisms. Moreover, due to the advances in
      microfabrication techniques, that allowed progressively smaller microstructures
      to be constructed, DEP can now be used for the manipulation of nanobioparticles.
      The first research studies on the DEP of nanobioparticles started in the 1990s.
      Since then, many research groups have carried out outstanding work with DEP of
      nanobioparticles such as macromolecules, virus, and spores. However, the need of
      a critical report that integrates these findings is evident. The aim of the
      present review is to depict the state-of-the-art on the use of DEP for the
      separation of nanobioparticles and the potential trends of novel applications of
      this technique. This review compiles and analyzes the significant findings
      obtained by many researchers. This publication is intended to provide the reader
      with state-of-the-art information on many research studies focused on DEP to
      handle nanobioparticles.

PMID- 18072221
TI  - SU-8 as a structural material for labs-on-chips and microelectromechanical
      systems.
AB  - Since its introduction in the nineties, the negative resist SU-8 has been
      increasingly used in micro- and nanotechnologies. SU-8 has made the fabrication
      of high-aspect ratio structures accessible to labs with no high-end facilities
      such as X-ray lithography systems or deep reactive ion etching systems. These low
      cost techniques have been applied not only in the fabrication of metallic parts
      or molds, but also in numerous other micromachining processes. Its ease of use
      has made SU-8 to be used in many applications, even when high-aspect ratios are
      not required. Beyond these pattern transfer applications, SU-8 has been used
      directly as a structural material for microelectromechanical systems and
      microfluidics due to its properties such as its excellent chemical resistance or
      the low Young modulus. In contrast to conventional resists, which are used
      temporally, SU-8 has been used as a permanent building material to fabricate
      microcomponents such as cantilevers, membranes, and microchannels. SU-8-based
      techniques have led to new low-temperature processes suitable for the fabrication
      of a wide range of objects, from the single component to the complete lab-on
      chip. First, this article aims to review the different techniques and provides
      guidelines to the use of SU-8 as a structural material. Second, practical
      examples from our respective labs are presented.

PMID- 18072222
TI  - Transport of charged samples in fluidic channels with large zeta potentials.
AB  - In this article, we present an analysis on the transport of charged samples
      through micro- and nanofluidic channels with large zeta potentials (|zeta| >
      (kBT)/e). Using the Method of Moments formulation, the diffusion-convection
      equation has been solved to evaluate the mean velocity and the dispersion of
      analyte bands in a parallel-plate device under electrokinetically- and pressure
      driven flow conditions. The effect of electromigration induced by the lateral
      electric field within the Debye layer has been quantified in our work using a
      Peclet number (Pe t) based on the characteristic electrophoretic velocity of the
      solute molecules in the transverse direction. It has been shown that while the
      effects of transverse electromigration on analyte transport only depends on the
      product Pe t zeta* for |zeta*| = (ezeta)/kBT << 1, both these parameters
      independently affect the flow of charged species in large zeta potential systems.
      For a given value of Pe t zeta*, the mean velocity and the slug dispersivity can
      vary by as much as an order of magnitude in going from a small zeta potential
      system (|zeta*| << 1) to a channel with |zeta*| = 4.

PMID- 18072223
TI  - Electrodeless direct current dielectrophoresis using reconfigurable field-shaping
      oil barriers.
AB  - We demonstrate dielectrophoretic (DEP) potential wells using pairs of insulating
      oil menisci to shape the DC electric field. These oil menisci are arranged in a
      configuration similar to the quadrupolar electrodes, typically used in DEP, and
      are shown to produce similar field gradients. While the one-pair well produces a
      focusing effect on particles in flow, the two-pair well results in creating
      spatial traps against crossflows. Uncharged polystyrene particles were used to
      map the DEP force fields and the experimental observations were compared against
      the field profiles obtained by numerically solving Maxwell's equations. We
      demonstrate trapping of a single particle due to negative DEP against a pressure
      driven crossflow. This can be easily extended to trap and hold cells and other
      objects against flow for a longer time. We also show the results of particle
      trapping experiments performed to observe the effect of adjusting the oil menisci
      and the gap between two pairs of menisci in a four-menisci configuration on the
      nature of the DEP well formed at the center. A design parameter, Theta, capturing
      the dimensions of the DEP energy well, is defined and simulations exploring the
      effects of different geometric features on Theta are presented.

PMID- 18072224
TI  - Channel wall coating on a poly-(methyl methacrylate) CE microchip by thermal
      immobilization of a cellulose derivative for size-based protein separation.
AB  - We demonstrate channel wall coating using a cellulose derivative on a poly
      (methyl methacrylate) (PMMA) CE microchip to eliminate EOF disturbing protein
      separation. The channel walls were modified by preconditioning with a solution
      containing the cellulose derivative and then thermally evaporating the solution
      to produce hydrophilic channel walls which prevent adsorption of analytes via a
      hydrophobic interaction. When the PMMA substrate was coated with the cellulose
      derivative hydroxypropylmethylcellulose (HPMC) 90SH, the water contact angle on
      the coated substrate was decreased (up to 15 degrees ) and EOF was significantly
      suppressed (up to 4.0 x 10(-6) cm2.V(-1)s(-1)). Three proteins (20.5, 68.0, and
      114.6 kDa) were successfully separated on the 0.15% HPMC 90SH-coated channel
      walls with good reproducibility of migration time (RSD <1.75%) and high
      efficiency (theoretical plate number per meter: 2.62 x 10(5)).

PMID- 18072225
TI  - Ionic liquid-assisted PDMS microchannel modification for efficiently resolving
      fluorescent dye and protein adsorption.
AB  - Herein, a hybrid system consisting of ionic liquid (IL) and nonionic surfactant
      has been successfully developed for dynamic modification of PDMS microchips and
      analyte adsorption such as fluoresent dyes and proteins has been efficiently
      suppressed. Mutual authentication between microchip electrophoresis and confocal
      laser scanning microscope was carried out to characterize the multiple novel
      functions of the IL-containing system and a possible mechanism was raised.
      Soluble IL used herein not only played the role as supporting electrolyte, but
      also provided increased EOF in the PDMS microchannel compared with common
      electrolytes such as phosphate buffer. Due to the high ionic conductivity of IL,
      on-column field-amplified sample stacking effect was four-fold higher than that
      without IL. Furthermore, an excellent synergistic effect existed between IL and
      nonionic surfactant, which enhanced the ability of resolving analyte adsorption
      to PDMS surface, and was demonstrated in the sensitive and efficient
      determination of rhodamine B (with detection limit of 8 nM) and a well separated
      mixture of proteins.

PMID- 18072226
TI  - Floating resistivity detector for microchip electrophoresis.
AB  - A newly developed conductivity detector, the floating resistivity detector (FRD),
      for microchip electrophoresis was introduced in this work. The detector design
      permits decoupling of the detection circuit from the high separation voltage
      without compromising separation efficiency. This greatly simplifies the
      integration of microchip electrophoresis systems. Its method of detection relies
      on platinum electrodes being dipped in two buffer-filled branched detection probe
      reservoirs on the microchip device. In this way, analytes passing through the
      detection window will not pass through and subsequently adsorb onto the
      electrodes, alleviating problems of electrode fouling due to analyte
      contamination and surface reactions. A customized microchip design was proposed
      and optimized stepwise for the new FRD system. Each branched detection probe was
      determined to be 4.50 mm long with a 0.075 mm detection window gap between them.
      The distance between the detection window and buffer waste reservoir was
      determined to be 1.50 mm. The optimized microchip design was subsequently used in
      the analysis of four groups of analytes - inorganic cations, amino acids,
      aminoglycosides antibiotics, and biomarkers. Based on the preliminary results
      obtained, the detection limits were in the range of 0.4-0.7 mg/L for the
      inorganic cations and 1.5-15 mg/L for the amino compounds.

PMID- 18072227
TI  - Conformational consequences of regio- and stereoselective disulfide bridge
      oxidation in a cyclic peptide.

PMID- 18072228
TI  - MR measurement of blood flow in the parotid gland without contrast medium: a
      functional study before and after gustatory stimulation.
AB  - PURPOSE: To investigate the feasibility of blood flow imaging in the parotid
      gland using the arterial spin labeling (ASL) technique for assessment of
      functional changes in the parotid gland after gustatory stimulation. MATERIALS
      AND METHODS: Anatomical and ASL imaging of the parotid gland was performed in
      eight healthy volunteers before and after gustatory stimulation over a period of
      17 min. All measurements were carried out in a 1.5 T whole-body MR unit. ASL and
      data recording were performed with an adapted FAIR TrueFISP (flow-sensitive
      alternating inversion-recovery true fast imaging with steady precession)
      technique. Maps of estimated tissue blood inflow in both parotid glands were
      derived using a simplified model and the extended Bloch equations. RESULTS:
      Delineation of the parotid glands was possible on FAIR TrueFISP images in all
      cases. In the 160 s period immediately after stimulation, a significant (P <
      0.01) mean increase of 62% in the estimated parotid blood flow was observed.
      Estimated baseline blood flow before gustatory stimulation ranged from 226 to 500
      mL/min/100 g (mean +/- SD 335 +/- 86). These rates increased in the 160 s
      immediately after stimulation to 404-772 mL/min/100 g (mean 542 +/- 108). In all
      volunteers, blood flow returned to near baseline values within the observation
      period. No statistically significant difference between the right and left
      parotid was observed in baseline and peak blood flow. CONCLUSION: ASL FAIR
      TrueFISP is feasible for functional characterization of the parotid glands.
      Assessment of changes in blood flow in the parotid gland could serve as a
      diagnostic tool in patients suffering from xerostomia.

PMID- 18072229
TI  - Disulfide symmetric dimers as stable pre-hapten forms for bioconjugation: a
      strategy to prepare immunoreagents for the detection of sulfophenyl carboxylate
      residues in environmental samples.
AB  - A convenient, generic synthesis of bioconjugates from haptens with a thiol group
      has been established. The corresponding haptens are synthesized as stable
      symmetric dimmers through a disulfide bond that is reduced immediately before
      conjugation with the aid of a di(n-butyl)phenylphosphine polystyrene (DBPP)
      resin. This strategy was used to prepare haptenized biomolecules and to raise
      antibodies against short-alkyl-chain sulfophenyl carboxylates (X-C(z)-SPCs; X is
      the position of the benzylic group and z is the alkyl-chain length) formed after
      degradation of the widely used domestic and industrial linear alkylbenzene
      sulfonates (LASs) surfactants. Because of the complexity of the LASs technical
      mixture, homologous and pseudo-heterologous immunization strategies have been
      studied with the aim of broadening antibody recognition of the SPC family. With
      this purpose, two types of immunizing haptens have been synthesized and used to
      prepare bioconjugates and raise antibodies. Type-A bioconjugates (SPC(A)-protein)
      were prepared by synthesizing type-A haptens as stable symmetric dimers,
      generically 2,2'-dithiobis[5-{4-(N-ethylsulfamoyl)}phenylalkanoic acids] (X-C(z)
      S-SPC). On the other hand, type-B bioconjugates (SPC(B)-protein) were prepared by
      treating the carboxylic groups of the corresponding 4-sulfophenylalkanoic acids
      (X-C(z)-SPC) with the amino groups of the lysine residues by using classical
      carbodiimide procedures. Type-A haptens produced antibodies with a much higher
      avidity for the target analyte. Under competitive immunochemical configurations
      (As112/2-C(5)-ovalbumin), these antibodies can reach a limit of detection (LOD)
      of 40 ng L(-1) with an IC(50) value of 200 ng L(-1) for 3-C(6)-SPC, which opens
      up the possibility of trace contamination of edible waters by surfactants with 3
      C(6)-SPC as a marker of LAS pollution. A comparative study of the properties of
      the three families of polyclonal antibodies produced revealed that antibodies
      raised through pseudo-heterologous immunization strategies produced antibodies
      with a broader specificity versus the SPC family. These results indicate that
      this approach could be useful in avoiding synthetic difficulties associated with
      preparing haptens that preserve all the most important chemical functionalities
      of the molecule.

PMID- 18072230
TI  - Multiple aromatic amination mediated by a diiron complex.

PMID- 18072231
TI  - Two-photon absorption cross-sections of reference dyes: a critical examination.
AB  - The electronic structure and one- and two-photon absorption spectra of four
      fluorophores, p-bis(o-methoxystyryl)benzene (Bis-MSB), coumarin 307, fluorescein
      and rhodamine B, commonly used as reference compounds for two-photon absorption
      spectra, have been theoretically calculated and compared with available
      experimental data. The possible reasons for the wide discrepancies in two-photon
      absorption cross-sections reported in the literature are discussed on the basis
      of the theoretical findings. The role of a solvent environment on the electronic
      one- and two-photon absorption spectra is also studied. We highlight some
      necessary precautions that one needs to take when comparing literature results of
      two-photon absorption cross-sections.

PMID- 18072232
TI  - Photoelectrochemical manifestation of photoelectron transport properties of
      vertically aligned nanotubular TiO2 photoanodes.
AB  - A simple photoelectrochemical method was proposed to quantitatively evaluate the
      electron transport process of photoelectrocatalytic oxidation of water at
      vertically aligned nanotubular TiO2 photoanodes. The photoelectrocatalysis
      reaction resistance (R=k/J(sph)+R(0)=R(I)+R(0)) was measured and used to express
      the electron transport characteristics of a nanotubular TiO(2) electrode. The
      overall resistance was found to consist of a variant (R(I)) and an invariant
      component (R(0)). R(I) was found to be inversely proportional to the saturation
      photocurrent and it depends on the experimental conditions. The proportional
      constant, k, represents the minimum applied potential bias required to remove 100
      % of the photogenerated electrons from the photocatalyst layer and was found to
      be independent of the anodization time. The invariant component of the resistance
      (R(0)) is an inherent property of the semiconductor photocatalyst that represents
      the sum of Ohmic contact impedance at the conducting substrate/TiO2 interface and
      crystalline boundary impedance. The magnitude of R(0) linearly increased with
      anodization time. The real saturated photocurrent density (J(real-sphd)) was
      found to be independent of R(0) indicating that the electron collection
      efficiency is independent of the nanotube length.

PMID- 18072233
TI  - Predicting response and resistance to endocrine therapy: profiling patients on
      aromatase inhibitors.
AB  - Selection for endocrine therapy requires the identification of markers that
      accurately predict response/resistance. In this report, the authors review their
      published work and abstract results from an unpublished study to illustrate the
      potential of RNA microarrays from sequential tumor biopsies from patients who
      were offered neoadjuvant endocrine therapy treatment to identify the molecular
      signatures associated with tumor sensitivity/resistance. Clinical response was
      assessed by serial ultrasound measurements in postmenopausal women with large,
      primary, estrogen receptor-rich breast cancers who received neoadjuvant treatment
      with letrozole for 3 months. Tumor RNA from biopsies that were taken before and
      after 14 days of treatment was hybridized on Affymetrix U133A chips to determine
      expression profiles. Classic estrogen-dependent genes and markers of
      proliferation were changed with treatment in most tumors but were poorly
      associated with clinical response (they frequently were changed in letrozole
      resistant tumors). Differential expression patterns could be used to identify
      heterogeneity in clinically resistant tumors. The results indicated that
      molecular profiling of early changes with letrozole treatment offers the
      opportunity to distinguish between clinically responsive and nonresponsive tumors
      and provides important information about the heterogeneity of endocrine
      resistance.

PMID- 18072234
TI  - Pharmacogenomics of tamoxifen and aromatase inhibitors.
AB  - In selection of therapy for women with breast cancer, the focus has been almost
      exclusively on the characteristics of the tumor, eg, estrogen receptor (ER) and
      HER-2. Until recently, essentially no attention has been paid to the host and her
      genetic makeup as it relates to the metabolism of different drugs. The first real
      clinical application of pharmacogenetics in breast cancer management relates to
      tamoxifen's biotransformation to active anticancer metabolites. New information
      has arisen on the metabolism of tamoxifen to the active metabolite, 4 hydroxy-N
      desmethyl-tamoxifen (endoxifen). Endoxifen is a metabolite with antitumor
      activity and affinity for the ER that is similar to 4-hydroxy-tamoxifen, but 1
      that is normally present in substantially higher concentrations. CYP2D6 plays a
      central role in the metabolism to endoxifen and 1 published study shows that
      genotypic differences in CYP2D6 and use of CYP2D6 inhibitors has an impact on
      outcomes of women treated with tamoxifen. The aromatase inhibitors represent a
      major class of drugs in the armamentarium against breast cancer. The aromatase
      gene has been resequenced and functional genomics have been performed on the
      identified nonsynonymous coding single nucleotide polymorphisms showing
      significant decreases in levels of activity. These findings are consistent with a
      hypothesis that genetic variation in the CYP19 gene might be important in the
      activity of aromatase inhibitors. Currently, the emphasis is on examining
      multiple genes (thus pharmacogenomics) in pharmacodynamic and pharmacokinetic
      pathways in women receiving aromatase inhibitors for breast cancer.

PMID- 18072235
TI  - Enhancing endocrine response with novel targeted therapies: why have the clinical
      trials to date failed to deliver on the preclinical promise?
AB  - Acquired resistance to endocrine therapies has severely limited their long-term
      effectiveness in breast cancer. In recent years a clear rationale has developed
      for combining signal transduction inhibitors (STIs) with endocrine therapies to
      delay the emergence of acquired resistance and enhance endocrine responsiveness.
      A variety of biologic agents have been developed to target key proteins along the
      EGFR, HER2, MAPK, and P13K/Akt signal transduction cascades. While several of
      these agents have shown early promise in selected breast cancer models,
      translating these data into convincing clinical results has been generally
      disappointing to date. By applying more rigorous trial design and tumor selection
      criteria to future trials, it is much more likely that adding the new generation
      of targeted therapies can fulfill its promise in enhancing endocrine
      responsiveness and our ability to treat breast cancer patients.

PMID- 18072236
TI  - Functional neuroimaging of belief, disbelief, and uncertainty.
AB  - OBJECTIVE: The difference between believing and disbelieving a proposition is one
      of the most potent regulators of human behavior and emotion. When one accepts a
      statement as true, it becomes the basis for further thought and action; rejected
      as false, it remains a string of words. The purpose of this study was to
      differentiate belief, disbelief, and uncertainty at the level of the brain.
      METHODS: We used functional magnetic resonance imaging (fMRI) to study the brains
      of 14 adults while they judged written statements to be "true" (belief), "false"
      (disbelief), or "undecidable" (uncertainty). To characterize belief, disbelief,
      and uncertainty in a content-independent manner, we included statements from a
      wide range of categories: autobiographical, mathematical, geographical,
      religious, ethical, semantic, and factual. RESULTS: The states of belief,
      disbelief, and uncertainty differentially activated distinct regions of the
      prefrontal and parietal cortices, as well as the basal ganglia. INTERPRETATION:
      Belief and disbelief differ from uncertainty in that both provide information
      that can subsequently inform behavior and emotion. The mechanism underlying this
      difference appears to involve the anterior cingulate cortex and the caudate.
      Although many areas of higher cognition are likely involved in assessing the
      truth-value of linguistic propositions, the final acceptance of a statement as
      "true" or its rejection as "false" appears to rely on more primitive, hedonic
      processing in the medial prefrontal cortex and the anterior insula. Truth may be
      beauty, and beauty truth, in more than a metaphorical sense, and false
      propositions may actually disgust us.

PMID- 18072237
TI  - Small-world properties of nonlinear brain activity in schizophrenia.
AB  - A disturbance in the interactions between distributed cortical regions may
      underlie the cognitive and perceptual dysfunction associated with schizophrenia.
      In this article, nonlinear measures of cortical interactions and graph
      theoretical metrics of network topography are combined to investigate this
      schizophrenia "disconnection hypothesis." This is achieved by analyzing the
      spatiotemporal structure of resting state scalp EEG data previously acquired from
      40 young subjects with a recent first episode of schizophrenia and 40 healthy
      matched controls. In each subject, a method of mapping the topography of
      nonlinear interactions between cortical regions was applied to a widely
      distributed array of these data. The resulting nonlinear correlation matrices
      were converted to weighted graphs. The path length (a measure of large-scale
      network integration), clustering coefficient (a measure of "cliquishness"), and
      hub structure of these graphs were used as metrics of the underlying brain
      network activity. The graphs of both groups exhibited high levels of local
      clustering combined with comparatively short path lengths--features consistent
      with a "small-world" topology--as well as the presence of strong, central hubs.
      The graphs in the schizophrenia group displayed lower clustering and shorter path
      lengths in comparison to the healthy group. Whilst still "small-world," these
      effects are consistent with a subtle randomization in the underlying network
      architecture--likely associated with a greater number of links connecting
      disparate clusters. This randomization may underlie the cognitive disturbances
      characteristic of schizophrenia.

PMID- 18072238
TI  - Roles of larger conductance mechanosensitive channels (MscL) in sporulation and
      Act secretion in Streptomyces coelicolor.
AB  - Larger conductance mechanosensitive channels (MscL) is a conserved channel
      existing in eukarya, bacteria and archaea. The gene SCO3190 in Streptomyces
      coelicolor encodes an MscL homolog of Escherichia coli. To elucidate the
      physiological roles of MscL in S. coelicolor (Sc-MscL), deletion mutant was
      constructed. The Sc-MscL deletion brought sporulation ahead, and had no
      significant influence to antibiotic synthesis in S. coelicolor. When Sc-MscL was
      overexpressed in S. coelicolor, the colony of S. coelicolor was small and sleek
      with abundant blue pigment corresponding to actinorhodin (Act). Furthermore,
      abundant blue pigment displayed on hypoosmotic LB plates comparing to
      hyperosmotic R5 plates. These results suggested that Sc-MscL was involved into
      Act secretion and sporulation relating to osmotic stress response in S.
      coelicolor. Moreover, Sc-MscL showed possible functional pentamer by cross
      linking in vitro. It is first report about biochemical and functional
      characterization of MscL in S. coelicolor.

PMID- 18072239
TI  - Microbial diversity analysis of former salterns in southern Taiwan by 16S rRNA
      based methods.
AB  - The microbiota diversity of the former salterns in southern Taiwan was
      investigated by denaturing gradient gel electrophoresis (DGGE) and fluorescence
      in situ hybridization (FISH). Soil samples from three salterns were analyzed
      using DGGE and 16S rRNA from 502 colonies representing 5 archaea and 18 bacteria
      taxonomic groups. Each representative taxonomic group was further identified,
      whereas 8.7% of clones were unclassified microorganisms. Chromohalobacter,
      Halomonas and Virgibacillus are dominant in the Biemen saltern, Chiguensis
      saltern and Szutsau saltern, respectively. During FISH analysis, several
      taxonomic-specific probes were used. The DAPI-stained-cell count in the Szutsao
      saltern had a higher number of microorganisms (4.58 x 10(7) cell/cm(3)) than the
      other salterns. Archaea occupied 2.7-6.6% whereas bacteria accounted for 37.2
      52.9% of total microbial population at the three sites. Among these three
      sampling sites, the Szutsao saltern had the highest diversity in halophilic
      microbial composition, as indicated by DGGE and FISH.

PMID- 18072240
TI  - Hydrocarbon degradation by thermophilic Nocardia otitidiscaviarum strain TSH1:
      physiological aspects.
AB  - Indigenous thermophilic hydrocarbon degraders are of special significance for the
      bioremediation of oil-contaminated desert soils with ambient temperature of 45-50
      degrees C. The first objective of this study was to demonstrate the hydrocarbon
      degrading capability of Nocardia otitidiscaviarum TSH1 (DSM 45,036) which grows
      optimally at 50 degrees C. Analysis of the metabolic profile of the strain TSH1
      showed that it could metabolize phenol, intermediate-chain-length n -alkanes and
      some polycyclic aromatic hydrocarbons (PAHs) ranging in size from two to four
      fused rings efficiently, but not toluene and xylene. N. otitidiscaviarum TSH1 was
      able to survive and grow at phenol concentrations up to 875 mg l(-1). For the
      first time, the physiological response of a thermophilic Nocardia strain to
      poorly available hydrophobic compounds was also investigated. When grown on a
      mineral salt medium with hexadecane, N. otitidiscaviarum TSH1 showed very high
      affinity for the organic phase. Additionally, PAH-grown cells were considerably
      hydrophobic. The capacity of PAH-utilizing N. otitidiscaviarum TSH1 isolate to
      produce biosurfactants was also investigated. Fatty acids (C(14)-C(18)) were
      detected by GC-MS analysis during bacterial growth in PAH supplemented mineral
      media. High cell surface hydrophobicity and capability of N. otitidiscaviarum
      TSH1 to degrade different hydrocarbons at 50 degrees C may make it an ideal
      candidate to treat oil-contaminated desert soils.

PMID- 18072241
TI  - Synthesis and antibacterial activity of quinolone-based compounds containing a
      coumarin moiety.
AB  - A new series of quinolone-based compounds containing a coumarin moiety have been
      synthesized and studied for their antibacterial activity against a panel of gram
      positive and gram-negative bacteria, including methicillin-resistant
      Staphylococcus aureus (MRSA). The results of the antibacterial evaluation of N-[2
      (coumarin-3-yl)ethyl]piperazinyl quinolone derivatives in comparison with parent
      quinolones (norfloxacin, ciprofloxacin, and enoxacin) indicated that N-[2
      (coumarin-3-yl)-2-oxoethyl]ciprofloxacin derivative (compound 8b) showed
      comparable or more potent antibacterial activity with respect to the reference
      drugs against the test strains. Generally, in both gram-positive and gram
      negative bacteria, better results are obtained with cyclopropyl at the N-1
      position of the quinolone ring and 2-oxo- on the ethyl spacer of coumarin and
      piperazine rings.

PMID- 18072242
TI  - Syntheses and biological activities of benzimidazolo[2,1-b] benzo[e]thiazepin
      5(10H)-ones.
AB  - Substituted benzimidazolo[2,1-b]benzo[e]thiazepin-5(10H)-one derivatives were
      prepared in moderate to good yield by reaction of mercapto benzimidazole
      derivatives with 2-chloromethylbenzoyl chloride as a coupling component. Their
      structures were confirmed by elemental analysis, IR, NMR, and MS. Their
      antioxidant properties were evaluated by several methods: scavenging effect on
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, reducing power assay, and
      inhibition of lipid peroxidation. In DPPH assay, 3h exhibited an activity
      stronger than trolox. In the reducing power assay and inhibition of lipid
      peroxidation, compound 3a was more active than 3h and similar to trolox. The
      antidiabetic effect was also determined, and the antidiabetic activities were
      correlated with their antioxidant properties, compound 3a was the most active
      compound in the in-vivo experiments.

PMID- 18072243
TI  - Synthesis, antimycobacterial and antifungal evaluation of 3-arylaminopyrazine-2,5
      dicarbonitriles.
AB  - This paper describes preparation and biological evaluation of pyrazinamide
      analogues. Pyrazinamide with its simple structure gives a good opportunity for
      further modification regarding an increase of its antimycobacterial activity. We
      prepared a series of compounds derived from pyrazine-2,5-dicarbonitrile with
      arylamino substitution in position 3. All compounds were assayed in vitro against
      major Mycobacterium and various Fungi species. The best activity was found in 3
      {[3-(trifluoromethyl)phenyl]amino}pyrazine-2,5-dicarbonitrile 11 with the value
      of 6.25 micromol(-1) against M. tuberculosis H(37)Rv and moderate activity
      against minor Mycobacterium pathogens.

PMID- 18072244
TI  - Synthesis and in-vitro pharmacological evaluation of new 5-HT1A receptor ligands
      containing a benzotriazinone nucleus.
AB  - This paper reports the microwave-assisted synthesis and the binding assays on the
      5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors of new benzotriazinone derivatives, in
      order to identify selective ligands for the 5-HT(1A) subtype receptor.
      Conventional and microwave heating of the reactions were compared. Good yields
      and short reaction times are the main advantages of our synthetic route. More
      active compounds were selected and further evaluated for their binding affinities
      on D(1), D(2) dopaminergic and alpha(1), alpha(2) adrenergic receptors. The 3-(2
      (4-(naphthalen-1-yl)piperazin-1-yl)ethyl)benzo[d][1,2,3]triazin-4(3H)-one 5 with
      K(i)= 0.000178 nM was the most active and selective derivative for the 5
      HT(1A)receptor with respect to other serotonin receptors and the most selective
      derivative compared to dopaminergic and adrenergic receptors.

PMID- 18072246
TI  - Microbes and metals: interactions in the environment.
AB  - Research on the behaviour of microorganisms in geogenic or anthropogenic
      metallomorphic environments is an integral part of geomicrobiology. The
      investigation of microbial impact on the fate of minerals and geologically
      significant compounds of mining areas can lead to an understanding of
      biogeochemical cycles. Metabolic processes of microorganisms are the cause for
      the dissolution of minerals, and especially pyrite oxidation results in the
      generation of acid mine drainage which, in turn, leads to heavy metal
      contamination as a result of mining activities. On the other hand, microbial
      metabolism can also contribute to the formation of certain ore deposits over
      geological time. The adaptation to heavy metal rich environments is resulting in
      microorgansims which show activities for biosorption, bioprecipitation,
      extracellular sequestration, transport mechanisms, and/or chelation. Such
      resistance mechanisms are the basis for the use of microorganisms in
      bioremediation approaches. As only a small part of the worldwide occurring
      prokaryotes has been described yet, the understanding of the role bacteria play
      in a geogenic and pedogenic context is very likely to change deeply as soon as
      more habitat relevant microbial functions can be described. Examples for the
      identification of microbial processes from case studies may help to advance this
      field. The strongly interdisciplinary field of bio-geo-interactions spanning from
      the microorganism to the mineral holds much promise for future developments in
      both basic research as well as applied sciences.

PMID- 18072247
TI  - Temperature and pH effect on lindane removal by Streptomyces sp. M7 in soil
      extract.
AB  - This work was conducted to study the removal of gamma-hexachlorocyclohexane
      (lindane) in a soil extract liquid medium (SE) by Streptomyces sp. M7 and to
      determine the influence of pH and temperature on bacterial growth and pesticide
      removal in this medium. When Streptomyces sp. M7 was cultured in SE supplemented
      with lindane 100 microg l(-1 )at different initial pH, the maximum growth was
      observed at pH 7 and the microorganism was not able to grow at pH 5 and 9; the
      highest pesticide removal (70.4%) by Streptomyces sp. M7 was noted at an initial
      pH of 7 at 4 weeks of incubation. The maximum removal (70% approximately) was
      observed when the microorganism was incubated in SE at 30 degrees C; although the
      optimal temperature for Streptomyces sp. M7 growth, with and without lindane, was
      25 degrees C, and for the pesticide removal was 30 degrees C. The results of this
      study suggest that this actinomycete strain appears as an effective alternative
      in the remediation of lindane polluted sites.

PMID- 18072248
TI  - Biosorption of metal and salt tolerant microbial isolates from a former uranium
      mining area. Their impact on changes in rare earth element patterns in acid mine
      drainage.
AB  - The concentration of metals in microbial habitats influenced by mining operations
      can reach enormous values. Worldwide, much emphasis is placed on the research of
      resistance and biosorptive capacities of microorganisms suitable for
      bioremediation purposes. Using a collection of isolates from a former uranium
      mining area in Eastern Thuringia, Germany, this study presents three Gram
      positive bacterial strains with distinct metal tolerances. These strains were
      identified as members of the genera Bacillus, Micrococcus and Streptomyces. Acid
      mine drainage (AMD) originating from the same mining area is characterized by
      high metal concentrations of a broad range of elements and a very low pH. AMD was
      analyzed and used as incubation solution. The sorption of rare earth elements
      (REE), aluminum, cobalt, copper, manganese, nickel, strontium, and uranium
      through selected strains was studied during a time course of four weeks.
      Biosorption was investigated after one hour, one week and four weeks by analyzing
      the concentrations of metals in supernatant and biomass. Additionally, dead
      biomass was investigated after four weeks of incubation. The maximum of metal
      removal was reached after one week. Up to 80% of both Al and Cu, and more than
      60% of U was shown to be removed from the solution. High concentrations of metals
      could be bound to the biomass, as for example 2.2 mg/g U. The strains could
      survive four weeks of incubation. Distinct and different patterns of rare earth
      elements of the inoculated and non-inoculated AMD water were observed. Changes in
      REE patterns hint at different binding types of heavy metals regarding incubation
      time and metabolic activity of the cells.

PMID- 18072249
TI  - Microbial diversity of mine water at Zhong Tiaoshan copper mine, China.
AB  - Microbial diversity of mine water at Zhong Tiaoshan copper mine, Shanxi province,
      China, was analyzed using a culture-independent 16S rRNA gene (rDNA) based on
      cloning approach. A total of 59 Operational Taxonomic Units (OTUs) were obtained
      from 226 clones from all three samples (8 OTUs from sample SX1, 25 from SX2 and
      26 from SX3). 46 of them were representative OTUs and were sequenced. 93.5% of
      the total clones had sequences that were less than 5% difference from those in
      the nucleic acids database. The percentage of overlapping OTUs among samples was
      from 12.1% to 35.3%. Phylogenetic analysis indicated that 60.62% of the clones
      were affiliated with members of the Proteobacteria (alpha -3.10%, beta -24.78%,
      gamma -31.41%, delta -1.33%), whereas 29.20% of the clones were closely related
      to the Nitrospira (Leptospirillum ferrooxidans 20.80%, Leptospirillum ferriphilum
      0.88% and Leptospirillum group III 7.52%, respectively). The rest clones were
      affiliated with the Firmicutes (2.65%) and the Bacteroidetes (7.52%). The results
      of Principal Component Analysis (PCA) based on the percentages of OTUs and
      biogeochemical data revealed that biogeochemical properties affected the
      diversity of microbial communities in mine water. Especially, the pH value,
      temperature and different concentrations of elements such as lead, zinc, sulfur,
      iron and copper seemed to be key factors affecting the composition and structure
      of microbial communities in this study.

PMID- 18072250
TI  - Characterization of Antarctic psychrotrophic bacteria with antibacterial
      activities against terrestrial microorganisms.
AB  - Five-hundreds and eighty bacterial strains, isolated from various Antarctic
      marine sources and locations, were screened for antimicrobial activity against
      terrestrial microorganisms. Twenty-two Antarctic isolates (3.8%), mainly
      retrieved from the water column at Terra Nova Bay (Ross Sea), expressed
      antagonistic activity against one to three indicator organisms. Escherichia coli
      and Proteus mirabilis resulted as the more susceptible, followed by Micrococcus
      luteus and Bacillus subtilis. None of the isolates inhibited the growth of
      Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella enterica and the
      eukaryotic fungus Candida albicans. Active Antarctic isolates, identified by 16S
      rDNA sequencing and phenotypically characterized by classical methods, were
      phylogenetically affiliated to the Actinobacteria (16 strains) and the gamma
      Proteobacteria (6 strains). Inhibition patterns, as well as phenotypic
      characteristics, highly vary for different isolates, even though they were
      affiliated to the same genus or closely related to the identical microorganism
      retrieved from the database, suggesting that these features were more likely
      strain-rather than species-specific.Results obtained from the present study
      confirm previous observations and highlight the potentiality of Antarctic marine
      bacteria as novel source of antibacterial substances.

PMID- 18072251
TI  - The effect of superoxide dismutase deficiency on zinc toxicity in
      Schizosaccharomyces pombe.
AB  - Zinc is a metal which is a cofactor in many enzymes and a structural element in
      zinc finger motifs those are important in relation between DNA and regulator
      proteins. Little is known about uptake, distribution, toxicity and detoxification
      of zinc ions in cells. In this study, zinc toxicity and detoxification levels
      have been compared in wild type and Cu/Zn superoxide dismutase mutant (sod1Delta)
      cells of the fission yeast Schizosaccharomyces pombe. We evaluated the toxic
      levels of zinc, total zinc content, lipid peroxidation levels and catalase
      activities for both strains which were grown in medium containing different
      concentrations of zinc. sod1Delta mutant showed important growth retardation and
      has higher lipid peroxidation and catalase activities than wild type. Cu/Zn
      superoxide dismutase (SOD1) activity of wild type cells was markedly increased
      when they were treated with elevated levels of zinc. SOD1 mRNA level also
      significantly increased when the cells treated with higher concentrations of
      zinc. These results indicate that the mutant cells were more sensitive to zinc
      stress and seemed to have more oxidative intracellular environment than wild type
      cells. Our results support the idea that superoxide dismutase is an important
      factor for zinc detoxification in eukaryotes.

PMID- 18072252
TI  - Chromate reducing and plant growth promoting activities of psychrotrophic
      Rhodococcus erythropolis MtCC 7,905.
AB  - A psychrotrophic bacterial strain resistant to 300 mg l(-1) of Cr(6+) was
      isolated from metal contaminated soil samples from a site situated in the Indian
      Himalayan Region. Based on 16 S rRNA analysis the isolate showed maximum
      similarity to Rhodococcus erythropolis. Rhodococcus erythropolis MTCC 7,905
      reduced substantial amounts of Cr(6+) to Cr(3+) at 10 degrees C and showed plant
      growth promotion. The isolate offer promise as inoculant to promote plant growth
      of pea (Pisum sativum) in the presence of toxic Cr(6+) concentration. To the best
      of our knowledge this is the first report on a psychrotrophic strain belonging to
      species R. erythropolis and its functional characterization to reduce Cr(6+ )and
      promote plant growth at low temperature.

PMID- 18072253
TI  - Leukaemia in young children living in the vicinity of nuclear power plants.

PMID- 18072254
TI  - Endocrine and targeted manipulation of breast cancer: summary statement for the
      Sixth Cambridge Conference.
AB  - The Sixth Cambridge Conference on Endocrine and Targeted Manipulation of Breast
      Cancer was convened in Cambridge, Massachusetts on April 30 and May 1, 2007. The
      purpose of this multidisciplinary meeting of leaders in clinical and basic
      research and patient treatment was to assess the most recent data in the field,
      articulate current best practices, and identify the next steps to advance both
      patient care and research. Topics included a review of data from major recent and
      ongoing trials of endocrine treatment in patients with early breast cancer and
      from studies combining endocrine therapy with other treatment. The current status
      of breast cancer prevention efforts was examined. Preclinical models of response
      and resistance, initial efforts to profile tumor response and resistance during
      endocrine therapy in patients, and new developments in pharmacogenomics were also
      highlighted. In this article, a synopsis of the key issues discussed,
      conclusions, and recommendations are summarized; these are presented at greater
      length in the individual articles and accompanying Open Discussions that comprise
      the full conference proceedings. In the 2 years since the Fifth Conference, we
      have gained valuable follow-up data from key trials in early breast cancer, which
      have helped to clarify both the efficacy and safety and tolerability of the
      available strategies for endocrine therapy. Observations using endocrine agents
      in combination with other treatment have been similarly extended. More detailed
      analysis of preclinical models has improved our understanding of resistance to
      endocrine therapy, and efforts to explore these and other mechanisms in the
      clinic are now underway. All of this has and continues to contribute to a growing
      understanding of how to optimize the use of endocrine agents in both treating and
      preventing breast cancer.

PMID- 18072255
TI  - Preclinical modeling of endocrine response and resistance: focus on aromatase
      inhibitors.
AB  - The authors developed a breast cancer intratumoral aromatase model system to
      compare the antitumor efficacy of several aromatase inhibitors (AIs) and
      antiestrogens (AEs). Although the AI letrozole caused sustained growth
      inhibition, tumors eventually began to grow, even when treatment was maintained.
      For the current study, the mechanisms of resistance to letrozole during the
      course of treatment were investigated. Estrogen receptor alpha (ER-alpha) levels
      decreased below control levels in letrozole-resistant tumors. The decrease was
      simultaneous to an increase in phosphorylation of ER-alpha and an unaltered
      expression of progesterone receptor (PgR). Expression levels of HER-2, activated
      (phosphorylated) SHC-adaptor protein (p-Shc), growth factor receptor-bound
      protein 2 (Grb-2), p-Raf, phosphorylated mitogen-activated protein kinase kinase
      1/2 (p-Mekl/2), and phosphorylated mitogen-activated protein kinase (p-MAPK) were
      increased. When cells isolated from letrozole-resistant tumors (LTLTCa cells)
      were treated with inhibitors of the HER-2 signaling pathway, ER-alpha expression
      and estradiol-stimulated transactivation was restored. The HER-2 blocker
      trastuzumab also restored the sensitivity of LTLTCa cells to AIs and AEs. These
      findings suggested that there is crosstalk between ER and HER-2 signaling. To
      prevent activation of the HER-2 pathway and resistance to AIs, mice were treated
      with a combination of AIs and the ER down-regulator fulvestrant. There was no
      increase in HER-2 or p-MAPK expression, and tumor growth was inhibited
      significantly. When trastuzumab was added to unresponsive tumors under letrozole
      treatment, it significantly inhibited tumors growth compared with switching to
      trastuzumab alone. However, the trastuzumab plus letrozole combination was more
      effective than letrozole alone only in refractory breast tumors. These results
      suggested that blocking both ER and HER-2 signaling may delay the development of
      resistance to AIs in patients with recurrent breast cancer.

PMID- 18072256
TI  - Summary of aromatase inhibitor clinical trials in postmenopausal women with early
      breast cancer.
AB  - Five years of adjuvant therapy with tamoxifen was considered the gold-standard
      treatment for postmenopausal women with estrogen receptor-positive breast cancer
      for many years. Data from a core group of clinical trials investigating the
      safety and efficacy of aromatase inhibitors (AIs) have challenged this
      perception. These studies were designed to evaluate the safety and efficacy of
      AIs in the following clinical settings: 1) as initial adjuvant therapy (the
      Arimidex, Tamoxifen, Alone or in Combination trial, Breast International Group
      Trial 1-98), 2) in a "switched setting" after 2 to 3 years of treatment with
      tamoxifen (Arimidex-Nolvadex 95, the Austrian Breast and Colorectal Cancer Study
      Group 8 [ABCSG 8] trial, the Italian Tamoxifen Anastrozole study, the Intergroup
      Exemestane Study), and 3) in extended settings (National Cancer Institute of
      Canada Trial MA.17, ABCSG 6a, National Surgical Adjuvant Breast and Bowel Project
      33). The efficacy data from these studies suggested that AIs have added
      substantial benefit in terms of disease outcome. AIs were tolerated well, and
      patients who received them experienced fewer thrombolic events and less
      endometrial cancer, hot flashes, night sweats, and vaginal bleeding compared with
      patients who receive tamoxifen. However, patients who received tamoxifen had less
      skeletal events and accelerated bone resorption compared with women who received
      AIs. AIs should be considered when planning a patient's endocrine therapy, taking
      into account the differences in tolerability and end-organ effects of the classes
      of endocrine therapy. Outstanding issues to optimize AI therapy include
      identifying the optimal duration, agent, and patients for these therapies.

PMID- 18072257
TI  - Combining endocrine agents with chemotherapy: which patients and what sequence?
AB  - In metastatic breast cancer, attempts to improve response to therapy by combining
      hormones and chemotherapy began in the 1970s. Since then, several randomized
      trials comparing single-agent hormone therapy or chemotherapy versus sequential
      combinations of these agents have been performed. In the majority of those
      studies, an increased response rate or an increased time to progression was
      observed when chemotherapy was added to hormone therapy or when hormone therapy
      was added to chemotherapy. However, in few of those trials was the increased
      response rate statistically significant or the response duration significantly
      prolonged, and no studies reported an improvement in overall survival.
      Furthermore, the studies did not make the correct comparisons of 1) hormone
      therapy alone followed by chemotherapy alone versus hormone therapy and
      chemotherapy given concurrently or 2) chemotherapy alone followed by hormone
      therapy versus concurrent chemotherapy and hormone therapy. To truly be
      advantageous, concurrent treatment should provide an increased response rate and
      response duration compared with the added or overall response rate and response
      duration of the same agents used sequentially. In the adjuvant setting, the
      timing and sequencing of hormone therapy and chemotherapy also has not been
      studied well. However, it has been accepted widely that adjuvant chemotherapy
      should be completed before beginning tamoxifen. No trials examining concurrent
      versus sequential treatment have been performed with hormone therapy and
      chemotherapy in the premenopausal setting or with aromatase inhibitors and
      chemotherapy in postmenopausal women. Considering the demonstrated importance of
      the timing of chemotherapy and tamoxifen in the postmenopausal setting, these
      questions should be explored further.

PMID- 18072258
TI  - Mammography screening of women in their 40s: impact of changes in screening
      guidelines.
AB  - BACKGROUND: : In March 1997, the American Cancer Society (ACS) updated its
      recommended mammography screening interval for women ages 40-49 years from once
      every 1 to 2 years to once every year. At the same time, the National Cancer
      Institute (NCI), which had previously not recommended routine screening of women
      in their 40s, began recommending screening at 1 to 2-year intervals. These events
      occurred during the data collection phase of a prospective study of mammography
      screening and, thereby, provided an unexpected opportunity to examine the
      potential influences of changing guidelines on women's beliefs about how
      frequently they should obtain screening exams. METHODS: : This analysis included
      1451 African American and white women ages 40-79 years, who obtained an "index"
      screening exam between October 1996 and January 1998. In baseline and 2-year
      follow-up telephone interviews, respondents provided information on demographic,
      socioeconomic, health history, medical care, behavioral and psychosocial factors,
      and on how frequently they believed women of their age should obtain screening
      mammograms. RESULTS: : After the ACS and NCI announcements of new screening
      guidelines for women in their 40s, a significant increase in endorsement of
      annual screening among women ages 40-49 years was observed, consistent with the
      ACS recommendation for annual screening in that age group. No increase in
      endorsement of annual screening among women ages 50 years and older was evident
      during the same time period. CONCLUSIONS: : Women's beliefs about how frequently
      they should obtain mammography screenings appear to change in response to changes
      in recommendations of high-profile health organizations, particularly when those
      recommendations call for an increase in screening.

PMID- 18072259
TI  - Twenty-year disease and treatment-associated mortality rates of patients with
      Hodgkin lymphoma of clinical stages IIIB and IV prospectively treated with 3
      month anthracycline-based chemotherapy followed by extended high-dose radiation.
AB  - BACKGROUND: In 1981, the authors developed an original strategy combining 3
      cycles of doxorubicin (adriamycin), bleomycin, vinblastine, and dacarbazine
      (ABVD) or ABVD-like chemotherapy and extended high-dose radiation for treating
      patients with clinical stages IIIB and IV Hodgkin lymphoma (HL). In the current
      study, the authors analyzed the 20-year results of this treatment as applied to
      213 patients according to 2 successive trials. METHODS: All patients who
      responded to chemotherapy received extended high-dose radiation. The rates of
      complete remission (CR), freedom from disease progression (FFP), HL-specific
      survival (HLSS), second tumors and cardiac events, freedom from treatment
      associated mortality (FFTM), overall survival (OS), and event-free survival were
      calculated. RESULTS: In December 2006, the median follow-up of the surviving
      patients exceeded 13 years; 102 patients (48%) achieved a CR after chemotherapy
      and 178 patients (84%) did so after radiotherapy. The rates of FFP (61%, quasi
      stable after 6 years) and HLSS (81.6%, stable after 12 years) were found to be
      significantly higher in patients who achieved a CR after chemotherapy. The
      incidence of hematologic malignancies was 10.9% (with 10 of 12 events occurring
      within the first 7 years). The rates of solid tumors (32.4%), cardiac events
      (33.4%), and FFTM (65.6%) did not reach any plateau by 20 years and were found to
      be significantly associated with patient age. The 20-year OS rate was 48%.
      CONCLUSIONS: This combined modality treatment gave long-term results similar to
      those obtained using 6 to 8 cycles of ABVD. Response to the initial brief
      chemotherapy administration was found to be predictive of the FFP and HLSS rates.
      The low rate of FFTM was the result of extended high-dose radiation. The results
      of the current study should help to design future trials for treating patients
      with advanced stages of HL.

PMID- 18072260
TI  - A prospective pilot study of curative-intent stereotactic body radiation therapy
      in patients with 5 or fewer oligometastatic lesions.
AB  - BACKGROUND: It is hypothesized that oligometastatic disease represents a state of
      potentially curable, limited metastases. Stereotactic body radiation therapy
      (SBRT) is an option for patients who are not amenable to or do not want
      resection. METHODS: From 2001 to 2006, 121 patients with < or =5 detectable
      metastases were enrolled in 2 prospective studies that used curative-intent SBRT.
      Most patients were treated with 10 fractions of 5 Gray. Stereotactic radiosurgery
      was offered to patients with brain metastases. RESULTS: The 2-year overall
      survival (OS), progression-free survival (PFS), local control (LC), and distant
      control (DC) rates were 50%, 26%, 67%, and 34%, respectively; and the respective
      4-year rates values were 28%, 20%, 60%, and 25%. A greater net tumor volume
      predicted significantly worse OS, PFS, LC, and DC. Patients with breast cancer
      fared significantly better with respect to OS, PFS, LC, and DC; and patients with
      adrenal metastases had significantly worse OS, PFS, and DC despite the small
      number of such patients enrolled. Neither the number of metastatic lesions nor
      the number of organs involved was a significant predictor of outcome. Among 45
      patients who remained alive at the last follow-up, 29 patients had no evidence of
      disease, including 23 patients with > or =2 years of follow-up. CONCLUSIONS:
      Oligometastatic disease is a potentially curable state of distant cancer spread.
      In this hypothesis-generating analysis, patients with less volume burden of their
      metastatic disease and those with primary breast cancer fared better. SBRT
      delivered with curative intent in patients with limited metastases should be
      investigated further. The Southwest Oncology Group is developing a prospective
      protocol to treat women who have limited breast cancer metastases with SBRT.

PMID- 18072261
TI  - Strong immunohistochemical expression of fibroblast growth factor receptor 3,
      superficial staining pattern of cytokeratin 20, and low proliferative activity
      define those papillary urothelial neoplasms of low malignant potential that do
      not recur.
AB  - BACKGROUND: Papillary urothelial neoplasm of low malignant potential (PUNLMP) is
      a clinically significant lesion because recurrence occurs in approximately 35% of
      patients. To date, it is not possible to identify those cases that will recur
      based on conventional histopathologic assessment. The objective of the current
      study was to evaluate immunohistochemically tissue expression of fibroblast
      growth factor receptor 3 (FGFR3), cytokeratin 20 (CK20), and MIB-1 in
      nonrecurrent and recurrent PUNLMP. METHODS: FGFR3, CK20, and MIB-1 were
      investigated by immunohistochemistry (IHC) in 80 PUNLMP cases (41 nonrecurrent
      and 39 recurrent), in 4 cases of normal urothelium (NU), and in 5 cases of muscle
      invasive pT2 urothelial carcinoma (UC). Statistics included discriminant
      analysis. RESULTS: NU demonstrated a weak to moderate FRFG3 staining intensity, a
      superficial pattern of CK20 staining, and low proliferative activity. UC was
      found to have FGFR3 staining similar to NU, an abnormal CK20 expression, and high
      proliferative activity. The nonrecurrent PUNLMP group demonstrated strong FGFR3
      intensity in 80.5% of the cases (vs 56.4% of the recurrent cases), a superficial
      CK20 staining pattern in 53.7% of the cases (vs 28.2% of the recurrent cases),
      and a percentage of MIB-1-positive nuclei below the median value of all the
      PUNLMP cases in 61% of the cases (35.9% in the recurrent cases). The differences
      were statistically significant. Discriminant analysis based on these 3 features
      demonstrated that 67.5% of cross-validated grouped PUNLMP cases were correctly
      allocated, with 73.2% of the nonrecurrent and 61.5% of the nonrecurrent cases
      being correctly classified. The specificity and sensitivity were 73.1% and 61.5%,
      respectively. CONCLUSIONS: Strong immunohistochemical expression of FGFR3, a
      superficial staining pattern of CK20, and a low proliferative activity define
      those papillary urothelial neoplasms of low malignant potential that do not
      recur.

PMID- 18072262
TI  - Editorial for "Mammography screening of women in their forties : the impact of
      changes in screening guidelines".

PMID- 18072263
TI  - Renal and cardiovascular morbidity after partial or radical nephrectomy.
AB  - BACKGROUND: To clarify the benefits of nephron-sparing surgery among patients
      with early-stage kidney cancer, the authors compared the frequency of renal and
      cardiovascular morbidity after partial or radical nephrectomy. METHODS: This
      retrospective cohort study was based on linked Surveillance, Epidemiology, and
      End Results-Medicare data. The authors identified 10,886 patients who underwent
      partial or radical nephrectomy between 1991 and 2002. Medical claims were
      examined for the occurrence of adverse renal and/or cardiovascular outcomes, and
      multivariate survival models were fit to estimate the association between type of
      surgery and each clinical outcome, using propensity scores to balance the
      treatment cohorts with respect to measured patient and disease characteristics.
      To control for secular trends in the indications for partial nephrectomy,
      separate analyses were performed based on treatment era (1991-1999 or 2000-2002).
      RESULTS: During the study interval, 10,123 patients (93%) and 763 patients (7%)
      underwent radical or partial nephrectomy, respectively. During 2000 to 2002,
      patients who underwent partial nephrectomy experienced fewer adverse renal
      outcomes (16.4% vs 21.8%; adjusted hazard ratio, 0.74; 95% confidence interval,
      0.58-0.94), including a trend toward less frequent receipt of dialysis services,
      dialysis access surgery, or renal transplantation. The likelihood of adverse
      cardiovascular outcomes did not differ by treatment. CONCLUSIONS: Among
      contemporary patients, partial nephrectomy was associated with less clinically
      apparent renal morbidity than radical nephrectomy. This finding motivates
      expanded use of partial nephrectomy among patients with early-stage kidney
      cancer. Given the potential for selection bias and residual confounding in this
      observational cohort, additional prospective studies will be necessary to
      validate the current findings.

PMID- 18072264
TI  - Value of endoscopic ultrasound staging in conjunction with the evaluation of
      lymphovascular invasion in identifying low-risk esophageal carcinoma.
AB  - BACKGROUND: With increasing emphasis on endoscopic therapy (ET) for T1 esophageal
      carcinoma, the identification of low-risk patients is critical. It was
      hypothesized that endoscopic ultrasonography (EUS) in concert with detailed
      histopathologic evaluation would identify low-risk cancers for an appropriate but
      organ-preserving strategy. METHODS: All patients who had pretreatment EUS and
      underwent esophagectomy as primary therapy for esophageal cancer between 1999 and
      2006 were analyzed retrospectively. The accuracy of EUS in predicting the correct
      pathologic stage was assessed along with a histopathologic reevaluation including
      lymphovascular invasion (LVI). Pathologic stage and various features were
      incorporated into a multivariate logistic regression model. RESULTS: A total of
      consecutive 87 esophageal cancer patients (81 with adenocarcinoma) were evaluable
      for this analysis. EUS correctly diagnosed 59 T1 cancers and 20 T2-4 cancers but
      understaged cancers in 2 patients and overstaged cancers in 6 patients. EUS
      correctly identified 8 patients with lymph node metastases but not 13 other
      patients. The accuracy, sensitivity, and specificity of EUS for T1 cancers were
      91%, 91%, and 91%, respectively; for T1a (intramucosal) cancers, the accuracy,
      sensitivity, and specificity were: 82%, 67%, and 93%, respectively, and for lymph
      node involvement these same values were 81%, 38%, and 94%, respectively. LVI was
      found to be an independent predictor of lymph node metastases on the multivariate
      analysis (P = .02). CONCLUSIONS: Data from the current study demonstrate that EUS
      has excellent accuracy, sensitivity, and specificity (91% each) for identifying
      T1 esophageal cancers and LVI is an independent predictor of lymph node
      metastases. A strategy for preservation of the esophagus may be possible in
      patients who have EUS-designated T1 cancer without LVI after successful ET.

PMID- 18072265
TI  - The chiral pyrethroid cycloprothrin: stereoisomer synthesis and separation and
      stereoselective insecticidal activity.
AB  - The synthesis and separation of the isomers of the pesticide cycloprothrin have
      been realized for the first time. Complete separation was achieved on a DAICEL
      CHIRALCEL OJ-H column (25 x 0.46 cm) for (1R, alpha*)-cycloprothrin isomers and
      on a DAICEL CHIRALCEL OD-H column (25 x 0.46 cm()) for (1S, alpha*)-cycloprothrin
      isomers. The insecticidal activity of (1R, alphaR)-cycloprothrin for the larvae
      of Mythimaseparata and Aphismedicagini was found to be about six times and four
      times higher, respectively, than that of racemic cycloprothrin.

PMID- 18072266
TI  - Stereochemical comparison of nebivolol with other beta-blockers.
AB  - beta-Blockers are widely used in the treatment of cardiovascular disease and act
      by antagonizing the effects of adrenaline (epinephrine) and noradrenaline
      (norepinephrine) on beta-adrenergic receptors. All beta-blockers currently used
      in the treatment of cardiovascular disease contain at least one chiral center
      and, while most are marketed as racemates, their cardiac antihypertensive
      activity generally resides in the S-enantiomer. Nebivolol is a third generation
      beta-blocker that is highly selective for the beta(1)-adrenoceptor. The nebivolol
      molecule contains four chiral centers and is marketed as a racemate of (+)
      nebivolol (SRRR-configuration) and (-)-nebivolol (RSSS-configuration). Nebivolol
      differs from all other beta-blockers with a hydroxypropanolamine substructure in
      that its cardiac antihypertensive activity resides in the R-enantiomer at the
      hydroxy group, whereas all other beta-blockers have antihypertensive activity in
      the S-enantiomer. Two of the four chiral centers in nebivolol are part of a ring
      structure and the increased rigidity of this structure may be related to
      nebivolol's divergence from the standard pharmacophore model of beta-blockers.

PMID- 18072267
TI  - Tongue cancer patients have a high frequency of allelic loss at the von Hippel
      Lindau gene and other loci on 3p.
AB  - BACKGROUND: Although genetic abnormalities on 3p have been suggested to be linked
      to the development of squamous cell carcinoma of the head and neck, to the
      authors' knowledge no study to date has examined such genetic abnormalities in
      patients with squamous cell carcinoma of the tongue. In the current study, loss
      of heterozygosity (LOH) was evaluated at several loci within 3p, including the
      von Hippel-Lindau gene (VHL), in samples of tongue squamous cell carcinoma. In
      addition, the coding region of the intact VHL allele was screened for sequence
      mutations. METHODS: DNA was extracted from tumor and nontumor tissues collected
      from 28 patients with tongue squamous cell carcinoma. LOH was investigated by
      analysis of single nucleotide polymorphisms within exon 3 of VHL and by
      microsatellite analysis within another 10 loci. Mutation analysis of the VHL gene
      was performed by polymerase chain reaction (PCR) amplification and sequencing of
      the coding region of the gene. RESULTS: LOH within VHL was found at a high
      frequency (45.5%) within the tumor. However, mutations of the VHL gene were not
      detected in all tumor samples. LOH of other microsatellite markers on 3p was
      observed in 27.3% to 50% of tumor samples. Eleven (58%) of 19 samples that were
      informative at more than 2 loci exhibited LOH of at least 1 locus; 10 of these 11
      cases exhibited LOH at multiple loci. CONCLUSIONS: A wide range of deletions in
      3p, including at the VHL gene, may play a role in the development of tongue
      cancer.

PMID- 18072268
TI  - Intraarterial chemotherapy and osmotic blood-brain barrier disruption for
      patients with embryonal and germ cell tumors of the central nervous system.
AB  - BACKGROUND: The rate of durable responses in embryonal and certain germ cell
      tumors of the central nervous system (CNS) is unsatisfactory. Intraarterial
      chemotherapy and osmotic blood-brain barrier disruption (IA/BBBD) increases drug
      delivery to the CNS. METHODS: Data of patients treated with carboplatin or
      methotrexate-based IA/BBBD on prospective phase 2 trials conducted at 3 centers
      were collected. Study outcomes included overall survival (OS), time to
      progression (TTP), and toxicity. RESULTS: Fifty-four patients were treated.
      Twenty-seven patients received IA/BBBD as salvage treatment. The median OS was
      2.8 years for all patients, 2.5 years for supratentorial and disseminated
      primitive neuroectodermal tumors (PNETs, n = 29), 1.7 years for medulloblastomas
      (n = 12), and 5.4 years for germ cell tumors (n = 13). OS and TTP for all
      patients were better with a Karnofsky Performance Status > or =70% (P = .0013 and
      .0070) and IA/BBBD as first-line treatment (P = .0059 and .029). In PNETs, OS was
      higher with pineal location (P = .045) and IA/BBBD as first-line treatment (P =
      .0036), and TTP was improved with radiotherapy before IA/BBBD (P = .036) and
      IA/BBBD as first-line treatment (P = .0079). Seventeen of 54 patients (31%) are
      alive, and 16 are alive at 4+ to 18+ years. Three survivors were not treated with
      radiotherapy and 4 were treated with focal radiotherapy only. The patients who
      were not irradiated did not develop dementia. CONCLUSIONS: Survival and toxicity
      data appear promising, considering the cohort's adverse prognostic profile. A
      plateau in survival curves suggests a cure for some patients. Long-term survival
      may be achieved with focal or reduced-dose radiotherapy in some IA/BBBD patients.

PMID- 18072270
TI  - Evidence of a four-hit mechanism involving SMARCB1 and NF2 in schwannomatosis
      associated schwannomas.
AB  - Schwannomatosis is characterized by the onset of multiple intracranial, spinal,
      or peripheral schwannomas, without involvement of the vestibular nerve, which is
      instead pathognomonic of neurofibromatosis type 2 (NF2). Recently, a
      schwannomatosis family with a germline mutation of the SMARCB1 gene on chromosome
      22 has been described. We report on the molecular analysis of the SMARCB1 and NF2
      genes in a series of 21 patients with schwannomatosis and in eight
      schwannomatosis-associated tumors from four different patients. A novel germline
      SMARCB1 mutation was found in one patient; inactivating somatic mutations of NF2,
      associated with loss of heterozygosity (LOH) of 22q, were found in two
      schwannomas of this patient. This is the second report of a germline SMARCB1
      mutation in patients affected by schwannomatosis and the first report of SMARCB1
      mutations associated with somatic NF2 mutations in schwannomatosis-associated
      tumors. The latter observation suggests that a four-hit mechanism involving the
      SMARCB1 and NF2 genes may be implicated in schwannomatosis-related tumorigenesis.

PMID- 18072271
TI  - Aging and the interaction of sensory cortical function and structure.
AB  - Even the healthiest older adults experience changes in cognitive and sensory
      function. Studies show that older adults have reduced neural responses to sensory
      information. However, it is well known that sensory systems do not act in
      isolation but function cooperatively to either enhance or suppress neural
      responses to individual environmental stimuli. Very little research has been
      dedicated to understanding how aging affects the interactions between sensory
      systems, especially cross-modal deactivations or the ability of one sensory
      system (e.g., audition) to suppress the neural responses in another sensory
      system cortex (e.g., vision). Such cross-modal interactions have been implicated
      in attentional shifts between sensory modalities and could account for increased
      distractibility in older adults. To assess age-related changes in cross-modal
      deactivations, functional MRI studies were performed in 61 adults between 18 and
      80 years old during simple auditory and visual discrimination tasks. Results
      within visual cortex confirmed previous findings of decreased responses to visual
      stimuli for older adults. Age-related changes in the visual cortical response to
      auditory stimuli were, however, much more complex and suggested an alteration
      with age in the functional interactions between the senses. Ventral visual
      cortical regions exhibited cross-modal deactivations in younger but not older
      adults, whereas more dorsal aspects of visual cortex were suppressed in older but
      not younger adults. These differences in deactivation also remained after
      adjusting for age-related reductions in brain volume of sensory cortex. Thus,
      functional differences in cortical activity between older and younger adults
      cannot solely be accounted for by differences in gray matter volume.

PMID- 18072272
TI  - Family history of cancer: is it an accurate indicator of cancer risk in the
      immigrant population?
AB  - BACKGROUND: Patients' self-reports of family history of cancer influence
      physician cancer screening recommendations. Little is known about rates of
      reporting a family history of cancer in the immigrant population. METHODS: The
      study used a nationally representative probability sample of adults, 18 years of
      age and older, living in the United States (N=5010) who had responded to the 2005
      Health Information Trends Survey (HINTS). Likelihood of reporting a family
      history of cancer was examined as a function of nativity status (foreign-born vs
      US-born) and control variables. RESULTS: Immigrants were approximately one-third
      as likely as nonimmigrants to report a family history of cancer (odds ratio [OR],
      0.35; 95% confidence index [95% CI], 0.25-0.48) after controlling for
      sociodemographic and cancer knowledge variables. CONCLUSIONS: When healthcare
      providers are assessing cancer risk and making screening recommendations, they
      should take into account that among foreign-born patients, and especially
      nonwhite foreign-born patients, self-reported family history of cancer (FHC) may
      misrepresent their cancer risk. Failure to account for low rates of reporting FHC
      among immigrants could inadvertently contribute to existing disparities in cancer
      screening and use of genetic testing by immigrants and ethnic minorities.

PMID- 18072273
TI  - Underuse of colorectal cancer screening in a cohort of Medicare beneficiaries.
AB  - BACKGROUND: To the authors' knowledge, few population-based studies to date have
      considered the serial use of colorectal cancer screening tests, which are usually
      recommended at specific intervals. METHODS: The study included a cohort of cancer
      free Medicare beneficiaries aged >or= 70 years who were identified in 1998.
      Inpatient, physician, and outpatient Medicare claims for colorectal screening
      procedures from 1991 through 1997 and 1998 through 2004 were used to categorize
      patients as receiving previous and subsequent complete screening, respectively.
      Codes were also used to identify patients at increased neoplasia risk. Cox
      proportional hazards models were used to measure time to receipt of complete
      screening in follow-up. RESULTS: The cohort consisted of 153,469 Medicare
      beneficiaries. Previous complete screening was performed in 29.2% of the cohort,
      including 76.7% of the increased risk group and 22.9% of other patients (P<
      .001). In the entire study cohort, the criteria for complete screening during the
      follow-up period were met in only 25.4% of patients, and included colonoscopy
      (17.6%), flexible sigmoidoscopy (2.9%), yearly fecal occult blood testing (0.8%),
      barium enema (0.1%), and >1 method (4.1%). Subsequent screening was strongly
      associated with receipt of previous screening (35.7% vs 21.2% of others; P<
      .001), and was also more frequent in younger and white patients. The differences
      were maintained in multivariate analysis. CONCLUSIONS: In a population-based
      cohort of Medicare beneficiaries, despite insurance reimbursement, there is
      significant underuse of colorectal testing. Given the ability of screening tests
      to reduce cancer incidence and mortality, continued efforts to promote screening
      are clearly warranted.

PMID- 18072274
TI  - Childhood cancer epidemiology in low-income countries.
AB  - Global studies of childhood cancer provide clues to cancer etiology, facilitate
      prevention and early diagnosis, identify biologic differences, improve survival
      rates in low-income countries (LIC) by facilitating quality improvement
      initiatives, and improve outcomes in high-income countries (HIC) through studies
      of tumor biology and collaborative clinical trials. Incidence rates of cancer
      differ between various ethnic groups within a single country and between various
      countries with similar ethnic compositions. Such differences may be the result of
      genetic predisposition, early or delayed exposure to infectious diseases, and
      other environmental factors. The reported incidence of childhood leukemia is
      lower in LIC than in more prosperous countries. Registration of childhood
      leukemia requires recognition of symptoms, rapid access to primary and tertiary
      medical care (a pediatric cancer unit), a correct diagnosis, and a data
      management infrastructure. In LIC, where these services are lacking, some
      children with leukemia may die before diagnosis and registration. In this
      environment, epidemiologic studies would seem to be an unaffordable luxury, but
      in reality represent a key element for progress. Hospital-based registries are
      both feasible and essential in LIC, and can be developed using available training
      programs for data managers and the free online Pediatric Oncology Networked Data
      Base (www.POND4kids.org), which allows collection, analysis, and sharing of data.

PMID- 18072275
TI  - Gremlin localization and expression levels partially differentiate idiopathic
      interstitial pneumonia severity and subtype.
AB  - Idiopathic pulmonary fibrosis (IPF) (histopathology of usual interstitial
      pneumonia, UIP) and non-specific interstitial pneumonia (NSIP) are diseases
      characterized by loss of normal lung architecture and function. The differential
      diagnosis between IPF/UIP and NSIP may be difficult. The levels of bone
      morphogenetic protein (BMP)-4 antagonist gremlin are up-regulated in IPF/UIP. The
      present study was performed to clarify whether the localization or the mRNA
      expression of gremlin or BMP-4 could be used in the differential diagnosis or
      assessment of severity of IPF/UIP and NSIP. Gremlin and BMP-4 immunoreactivities
      were quantitated from 24 UIP and 12 NSIP lung specimens. Quantitative real-time
      polymerase chain reaction analyses were performed to compare gremlin and BMP-4
      expression between UIP (n = 8) and NSIP (n = 5) biopsies. Immunohistochemical
      positivity and mRNA levels were correlated to lung function parameters. In
      IPF/UIP biopsies, gremlin was detected mainly in the thickened lung parenchyma,
      whereas in NSIP it was observed in the alveolar epithelium. BMP-4-positive (BMP
      4+) cells were detected solely in the alveolar wall. The percentage of gremlin
      positive area was higher in IPF/UIP (5.1 +/- 0.6) than in NSIP (1.8 +/- 0.7) (n =
      36, p < 0.0001). Gremlin mRNA levels were higher in advanced UIP (p = 0.008) and
      NSIP (p = 0.007) biopsies than in the normal control lung. A negative correlation
      was found between the specific diffusion capacity corrected for alveolar volume
      (DLCO/VA) and gremlin mRNA levels (r = - 0.69, p = 0.007). The highest numbers of
      BMP-4+ cells were found in NSIP biopsies. BMP-4 mRNA levels correlated positively
      with forced vital capacity (r = 0.801, p < 0.0001) and diffusion capacity.
      Parenchymal gremlin immunoreactivity is thus suggestive of a UIP-type
      interstitial pneumonia. Gremlin expression levels correlating negatively and BMP
      4 levels positively with disease severity support recent observations of a
      fibroprotective role for the BMPs.

PMID- 18072276
TI  - Current NCI-sponsored Cooperative Group trials of endocrine therapies in breast
      cancer.
AB  - Over several decades, investigators working through National Cancer Institute
      sponsored Cooperative Groups have contributed to major advances in the endocrine
      treatment of breast cancer. Accomplishments include the benefit of tamoxifen
      therapy for early stage invasive and noninvasive breast cancer, the benefit of
      raloxifene and tamoxifen for prevention of breast cancer, the improved efficacy
      of tamoxifen after chemotherapy as opposed to concurrent administration, and the
      ability of letrozole administered after 5 years of tamoxifen to improve disease
      free survival. Most recently, Cooperative Group studies have contributed to the
      development of a molecular profiling test, Oncotype Dx, which identifies women
      who have an excellent prognosis with hormonal therapy alone. Ongoing phase 3
      clinical trials address the following questions: Is prolonged duration of
      aromatase inhibitor (AI) therapy beneficial? What is the efficacy and toxicity of
      steroidal versus nonsteroidal AIs in adjuvant treatment? Is combination hormonal
      therapy with an estrogen receptor down-regulator (fulvestrant) and an AI superior
      to an AI alone in the treatment of metastatic breast cancer? Does ovarian
      suppression offer superior benefit to standard therapy in the treatment of
      premenopausal breast cancer? What is the role of chemotherapy for early stage
      breast cancer selected via molecular profiling analysis? How can targeted
      therapies be used effectively in combination? Studies in subsets of patients
      defined by molecular profiling will be necessary to fully define breast cancer
      subtypes and realize the promise of personalized medicine. Close research
      partnerships that promote large-scale translational research are essential to the
      continuation of rapid achievements in this field.

PMID- 18072277
TI  - Selective neurophysiologic responses to music in instrumentalists with different
      listening biographies.
AB  - To appropriately adapt to constant sensory stimulation, neurons in the auditory
      system are tuned to various acoustic characteristics, such as center frequencies,
      frequency modulations, and their combinations, particularly those combinations
      that carry species-specific communicative functions. The present study asks
      whether such tunings extend beyond acoustic and communicative functions to
      auditory self-relevance and expertise. More specifically, we examined the role of
      the listening biography--an individual's long term experience with a particular
      type of auditory input--on perceptual-neural plasticity. Two groups of expert
      instrumentalists (violinists and flutists) listened to matched musical excerpts
      played on the two instruments (J.S. Bach Partitas for solo violin and flute)
      while their cerebral hemodynamic responses were measured using fMRI. Our
      experimental design allowed for a comprehensive investigation of the
      neurophysiology (cerebral hemodynamic responses as measured by fMRI) of auditory
      expertise (i.e., when violinists listened to violin music and when flutists
      listened to flute music) and nonexpertise (i.e., when subjects listened to music
      played on the other instrument). We found an extensive cerebral network of
      expertise, which implicates increased sensitivity to musical syntax (BA 44),
      timbre (auditory association cortex), and sound-motor interactions (precentral
      gyrus) when listening to music played on the instrument of expertise (the
      instrument for which subjects had a unique listening biography). These findings
      highlight auditory self-relevance and expertise as a mechanism of perceptual
      neural plasticity, and implicate neural tuning that includes and extends beyond
      acoustic and communication-relevant structures.

PMID- 18072278
TI  - Abnormal diffusion of cerebral white matter in early blindness.
AB  - Early visual deprivation may lead to both abnormal and plastic changes in the
      visual and other systems of the brain. Such secondary changes in the gray matter
      of the early blind have been well studied, but not so well in the cerebral white
      matter whose subtle changes may be revealed by diffusion tensor imaging. The
      first purpose of this study is to explore the possible changed white matter
      regions of the early blind in whole brain manners, using voxel-based analysis
      (VBA) and tract-based spatial statistics (TBSS) methods. The second purpose is to
      investigate the changes of diffusion eigenvalues in the abnormal white matter
      fiber tracts using tractography based group mapping analysis. From VBA of
      fractional anisotropy (FA) images, the significant changed white matter regions
      were the geniculocalcarine tract (GCT) and its adjacent regions. This finding was
      validated by TBSS method. Then we studied the changes of mean diffusivity (MD),
      FA, primary (lambda(1)) and transverse diffusivities (lambda(23)) in the GCT
      using tractography based group mapping analysis. We found the early blind had
      significantly lower FA (P < 0.0001), higher MD (P = 0.001) and lambda(23) (P <
      0.0001) in the GCT. This pattern of diffusion changes is similar to findings seen
      in immaturity or axonal degeneration. Thus, we suggest that transneuronal
      degeneration and/or immaturity may account for the abnormal diffusion changes in
      the GCT of the early blind.

PMID- 18072280
TI  - Neural activations at the junction of the inferior frontal sulcus and the
      inferior precentral sulcus: interindividual variability, reliability, and
      association with sulcal morphology.
AB  - The sulcal morphology of the human frontal lobe is highly variable. Although the
      structural images usually acquired in functional magnetic resonance imaging
      studies provide information about this interindividual variability, this
      information is only rarely used to relate structure and function. Here, we
      investigated the spatial relationship between posterior frontolateral activations
      in a task-switching paradigm and the junction of the inferior frontal sulcus and
      the inferior precentral sulcus (inferior frontal junction, IFJ) on an individual
      subject basis. Results show that, although variable in terms of stereotaxic
      coordinates, the posterior frontolateral activations observed in task-switching
      are consistently and reliably located at the IFJ in the brains of individual
      participants. The IFJ shares such consistent localization with other nonprimary
      areas as motion-sensitive area V5/MT and the frontal eye field. Building on
      tension-based models of morphogenesis, this structure-function correspondence
      might indicate that the cytoarchitectonic area underlying activations of the IFJ
      develops at early stages of cortical folding.

PMID- 18072281
TI  - Preceding attention and the dorsomedial prefrontal cortex: process specificity
      versus domain dependence.
AB  - The dorsomedial prefrontal cortex (DMPFC) has been shown to be involved in
      attending different states, all including a strong emotional component. It
      remains unclear, though, whether neural activity in the DMPFC is predominantly
      determined by either a particular domain, as emotional stimuli, or by a specific
      process, as attention. Here, we used functional magnetic resonance imaging to
      test the alternative hypotheses of domain- versus process-specificity in DMPFC.
      Subjects had to perceive pictures from three different domains, sexual,
      emotional, and neutral stimuli, in both a nonattended, i.e., unexpected, and
      attended, i.e., expected mode. Our results show DMPFC activation during attended,
      i.e., expected stimulus perception when compared with nonattended, i.e.,
      unexpected stimuli perception. DMPFC activation and corresponding behavioral
      changes (reaction time, subjective ratings) were observed in all three domains,
      sexual, emotional, and neutral stimuli. As opposed to those process-specific
      effects that were found predominantly in posterior DMPFC, a process by domain
      interaction was found to be characteristic for more anterior parts of the DMPFC.
      Taken together, our findings favour the hypothesis that neural activity in the
      posterior DMPFC is determined by a specific process, i.e., attending stimuli, and
      thus characterized by process-specificity rather than by a particular domain,
      i.e., sexual, emotional, or neutral stimuli, reflecting domain-specificity. This
      suggests that the anterior and posterior DMPFC is involved in the process of
      attending mental states while remaining more (posterior DMPFC) or less (anterior
      DMPFC) independent of the type or domain of the respective stimulus.

PMID- 18072279
TI  - Combining fMRI and SNP data to investigate connections between brain function and
      genetics using parallel ICA.
AB  - There is current interest in understanding genetic influences on both healthy and
      disordered brain function. We assessed brain function with functional magnetic
      resonance imaging (fMRI) data collected during an auditory oddball task-
      detecting an infrequent sound within a series of frequent sounds. Then, task
      related imaging findings were utilized as potential intermediate phenotypes
      (endophenotypes) to investigate genomic factors derived from a single nucleotide
      polymorphism (SNP) array. Our target is the linkage of these genomic factors to
      normal/abnormal brain functionality. We explored parallel independent component
      analysis (paraICA) as a new method for analyzing multimodal data. The method was
      aimed to identify simultaneously independent components of each modality and the
      relationships between them. When 43 healthy controls and 20 schizophrenia
      patients, all Caucasian, were studied, we found a correlation of 0.38 between one
      fMRI component and one SNP component. This fMRI component consisted mainly of
      parietal lobe activations. The relevant SNP component was contributed to
      significantly by 10 SNPs located in genes, including those coding for the
      nicotinic alpha-7 cholinergic receptor, aromatic amino acid decarboxylase,
      disrupted in schizophrenia 1, among others. Both fMRI and SNP components showed
      significant differences in loading parameters between the schizophrenia and
      control groups (P = 0.0006 for the fMRI component; P = 0.001 for the SNP
      component). In summary, we constructed a framework to identify interactions
      between brain functional and genetic information; our findings provide a proof-of
      concept that genomic SNP factors can be investigated by using endophenotypic
      imaging findings in a multivariate format.

PMID- 18072282
TI  - Colocalization of MCM8 and MCM7 with proteins involved in distinct aspects of DNA
      replication.
AB  - Minichromosome maintenance (MCM) proteins are essential for DNA replication in
      eukaryotes. A subcomplex of the MCM2-7 family members, initially characterized in
      yeast, is thought to serve as a eukaryotic DNA replicative helicase. MCM8 is a
      new family member, not present in yeast, which may function alone or with other
      family members in aspects of DNA metabolism, including replication initiation and
      elongation. Through the use of chromatin immunoprecipitation, we find that MCM8,
      like MCM7, colocalizes on a specific DNA segment of the c-MYC replication
      initiation zone (c-MYC replicator) with Cdc6, a protein potentially involved in
      loading MCM proteins onto DNA. The association between MCM8 and MCM7 peaks in mid
      G1, at the time of assembly of the prereplication complex. The association of
      both MCM proteins with Cdc6, however, continues even after DNA replication is
      complete. We also find that MCM8 colocalizes at the c-MYC replicator with
      chromatin-bound Cdk2. Our data indicate that any role MCM8 may play in elongation
      is likely to be discontinuous, in its association with DNA, from a potential role
      in initiation. Using immunogold electron microscopy we show that MCM8 and MCM7
      differ in spatial relation to RPA70 during S phase. Our data strongly suggest
      that MCM8 functions with other known replication proteins in processes which
      accompany DNA replication, especially initiation, and which are specifically
      adapted to suit higher eukaryotes.

PMID- 18072283
TI  - Practical considerations in the use of polarized light microscopy in the analysis
      of the collagen network in articular cartilage.
AB  - Polarized light microscopy is a traditional method for visualizing the collagen
      network architecture of articular cartilage. Articular cartilage repair and
      tissue engineering studies have raised new demands for techniques capable of
      quantitative characterization of the scar and repair tissues, including
      properties of the collagen network. Modern polarized light microscopy can be used
      to measure collagen fibril orientation, parallelism, and birefringence. New
      commercial instruments are computer controlled and the measurements are easy to
      perform. However, often the interpretation of results causes difficulties, even
      errors, because the theoretical aspects of the technique are demanding. The aim
      of this study was to describe the instrumentation and properties of a modern
      polarized light microscope, to point out some sources of error in the
      interpretation of the results, and to recall the theoretical background of the
      polarized light microscopy.

PMID- 18072284
TI  - Preservation and fluorescence of the microfossils from Neoproterozoic Doushantuo
      formation.
AB  - The phosphatized microfossils from Doushantuo Formation, Southeast China show us
      the biodiversity about 600 million years ago, which is a unique window for the
      evolution of the early life on earth. However, the process of phosphatic
      fossilization in detail still remains unknown. Here we report our study on the
      preservation state of the fossils by using confocal laser scanning microscopy. We
      found that fluorescent signal of the fossil could reflect the preservation state
      when compared with the transmission light microscopy. First, we found the
      fluorescent signal of the decayed cells of the fossil was weaker than that of the
      nondecayed part. Second, we found that the three-dimensional reconstruction of
      the fluorescent signals could help to judge the degree of mineralization of the
      fossil cells, compared with the observation by transmission light microscope.
      Third, we found that almost all of the fossil specimens we observed could
      fluoresce more or less when excited by laser light. Therefore, the fluorescent
      microscopy provides a useful method for the study of the preservation state of
      the phosphatic fossil cells.

PMID- 18072285
TI  - Mastoparan effects in skeletal muscle damage: An ultrastructural view until now
      concealed.
AB  - Animal venoms have been valuable sources for development of new drugs and
      important tools to understand cellular functioning in health and disease. The
      venom of Polybia paulista, a neotropical social wasp belonging to the subfamily
      Polistinae, has been sampled by headspace solid phase microextraction and
      analyzed by gas chromatography-mass spectrometry. Recent study has shown that
      mastoparan, a major basic peptide isolated from the venom, reproduces the
      myotoxic effect of the whole venom. In this study, Polybia-MPII mastoparan was
      synthesized and studies using transmission electron microscopy were carried out
      in mice tibial anterior muscle to identify the subcellular targets of its
      myotoxic action. The effects were followed at 3 and 24 h, 3, 7, and 21 days after
      mastoparan (0.25 mug/muL) intramuscular injection. The peptide caused disruption
      of the sarcolemma and collapse of myofibril arrangement in myofibers. As a
      consequence, fibers presented heteromorphic amorphous masses of agglutinated
      myofilaments very often intermingled with denuded sarcoplasmic areas sometimes
      only surrounded by a persistent basal lamina. To a lesser extent, a number of
      fibers apparently did not present sarcolemma rupture but instead appeared with
      multiple small vacuoles. The results showed that sarcolemma, sarcoplasmic
      reticulum (SR), and mitochondria were the main targets for mastoparan. In
      addition, a number of fibers showed apoptotic-like nuclei suggesting that the
      peptide causes death both by necrosis and apoptosis. This study presents a
      hitherto unexplored view of the effects of mastoparan in skeletal muscle and
      contributes to discuss how the known pharmacology of the peptide is reflected in
      the sarcolemma, SR, mitochondria, and nucleus of muscle fibers, apparently its
      subcellular targets.

PMID- 18072286
TI  - Functional characterization of P2Y1 versus P2X receptors in RBA-2 astrocytes:
      elucidate the roles of ATP release and protein kinase C.
AB  - A physiological concentration of extracellular ATP stimulated biphasic Ca(2+)
      signal, and the Ca(2+) transient was decreased and the Ca(2+) sustain was
      eliminated immediately after removal of ATP and Ca(2+) in RBA-2 astrocytes.
      Reintroduction of Ca(2+) induced Ca(2+) sustain. Stimulation of P2Y(1) receptors
      with 2-methylthioadenosine 5'-diphosphate (2MeSADP) also induced a biphasic
      Ca(2+) signaling and the Ca(2+) sustains were eliminated using Ca(2+)-free
      buffer. The 2MeSADP-mediated biphasic Ca(2+) signals were inhibited by
      phospholipase C (PLC) inhibitor U73122, and completely blocked by P2Y(1)
      selective antagonist MRS2179 and protein kinase C (PKC) activator phorbol 12
      myristate 13-acetate (PMA) whereas enhanced by PKC inhibitors GF109203X and
      Go6979. Inhibition of capacitative Ca(2+) entry (CCE) decreased the Ca(2+)
      induced Ca(2+) entry; nevertheless, ATP further enhanced the Ca(2+)-induced
      Ca(2+) entry in the intracellular Ca(2+) store-emptied and CCE-inhibited cells
      indicating that ATP stimulated Ca(2+) entry via CCE and ionotropic P2X receptors.
      Furthermore, the 2MeSADP-induced Ca(2+) sustain was eliminated by apyrase but
      potentiated by P2X(4) allosteric effector ivermectin (IVM). The agonist ADPbetaS
      stimulated a lesser P2Y(1)-mediated Ca(2+) signal and caused a two-fold increase
      in ATP release but that were not affected by IVM whereas inhibited by PMA, PLC
      inhibitor ET-18-OCH(3) and phospholipase D (PLD) inhibitor D609, and enhanced by
      removal of intra- or extracellular Ca(2+). Taken together, the P2Y(1)-mediated
      Ca(2+) sustain was at least in part via P2X receptors activated by the P2Y(1)
      induced ATP release, and PKC played a pivotal role in desensitization of P2Y(1)
      receptors in RBA-2 astrocytes.

PMID- 18072287
TI  - Maintenance of mitochondrial DNA copy number and expression are essential for
      preservation of mitochondrial function and cell growth.
AB  - To examine whether a reduction in the mtDNA level will compromise mitochondrial
      biogenesis and mitochondrial function, we created a cell model with depleted
      mtDNA. Stable transfection of small interfering (si)RNA of mitochondrial
      transcription factor A (Tfam) was used to interfere with Tfam gene expression.
      Selected stable clones showed 60-95% reduction in Tfam gene expression and 50-90%
      reduction in cytochrome b (Cyt b) gene expression. Tfam gene knockdown clones
      also showed decreased mtDNA-encoded cytochrome c oxidase subunit I (COX I)
      protein expression. However, no significant differences in protein expression
      were observed in nuclear DNA (nDNA)-encoded mitochondrial respiratory enzyme
      subunits. The cell morphology changed from a rhombus-like to a spindle-like form
      as determined in clones with decreased expressions of Tfam, mtRNA, and
      mitochondrial proteins. The mitochondrial respiratory enzyme activities and ATP
      production in such clones were significantly lower. The proportions of mtDNA
      mutations including 8-hydroxy-2'-deoxyguanosine (8-OHdG), a 4,977-bp deletion,
      and a 3,243-point mutation were also examined in these clones. No obvious
      increase in mtDNA mutations was observed in mitochondrial dysfunctional cell
      clones. The mitochondrial respiratory activity and ATP production ability
      recovered in cells with increased mtDNA levels after removal of the specific
      siRNA treatment. These experimental results provide direct evidence to
      substantiate that downregulation of mtDNA copy number and expression may
      compromise mitochondrial function and subsequent cell growth and morphology.

PMID- 18072288
TI  - BMP-6 over-expression in prostate cancer is associated with increased Id-1
      protein and a more invasive phenotype.
AB  - Bone morphogenetic protein-6 (BMP-6) has been strongly implicated in prostate
      cancer development and bone metastasis. Our previous data showed that BMP-6 mRNA
      was absent in patients with benign prostatic hyperplasia, but evident in primary
      tumours with established secondary skeletal metastases. To examine the role of
      BMP-6 in prostate cancer progression, we have developed a BMP-6-regulatable,
      doxycycline-inducible gene expression system. BMP-6 induction by doxycycline
      addition led to increased levels of BMP-6 RNA and protein, associated with
      nuclear translocation of SMADs and activation of the downstream target gene Id-1.
      BMP-6 protein did not enhance the proliferation rate of PC3M cells but did
      significantly increase the rate of migration and invasion in both PC3M and DU145
      cells. Increased metalloproteinase (MMP-1 and MMP-9) mRNA levels were also
      observed following BMP-6 induction. Luciferase reporter assays confirmed BMP-6
      mediated activation of MMP-1 and MMP-9 promoters, indicating direct
      transcriptional activation of MMPs by BMP-6. BMP-6 stimulation also led to an
      increase in phosphorylation levels of MAPK proteins. We next examined the effects
      of BMP-6 on the downstream gene Id-1 in a cohort of prostate cancer patients. A
      tissue microarray (TMA) was constructed and samples stained for BMP-6 and Id-1
      expression. We observed a significant increase in the intensity of staining of
      epithelial BMP-6 in the cancer cases compared to the benign cases (Mann-Whitney U
      test, p < 0.0005) and in the intensity of staining of epithelial Id-1 in the
      cancer cases compared to the benign cases (Mann-Whitney U test, p = 0.015). We
      further observed a significant positive correlation between epithelial staining
      for Id-1 and BMP-6 (p = 0.001) across all samples for both benign and cancer
      cases. These data demonstrate that BMP-6 promotes migration and invasion of
      prostate cancer cells, potentially through activation of Id-1 and MMP activation.

PMID- 18072289
TI  - Blood glucose monitoring. When to check and why.

PMID- 18072290
TI  - New tools 2007.

PMID- 18072291
TI  - National Diabetes Month. Do's and don't's for saving money.

PMID- 18072292
TI  - Fall harvest recipes.

PMID- 18072293
TI  - Diabetes quiz. How much do you know about fish?

PMID- 18072295
TI  - Supermarket smarts. Navigating the salad bar.

PMID- 18072294
TI  - Exercising the aging body. Part I: resistance and endurance.

PMID- 18072296
TI  - Is going organic the way to go?

PMID- 18072297
TI  - The food pyramid: what's in it for diabetes?

PMID- 18072298
TI  - For parents. When your teen just quits.

PMID- 18072299
TI  - [Babesiosis, a little known zoonosis].
AB  - Babesiosis is an emerging tick borne zoonotic disease caused by intraerythrocytic
      parasites of the genus Babesia. Babesiosis is one of the most common infections
      of free-living animals worldwide but is perhaps most prevalent in rodents,
      carnivores, and cattle. This fact increases the concern about the emerging
      zoonosis. Like the malaria agent Plasmodium, the parasite Babesia attacks and
      damages the host's red cells. Babesia microti and Babesia divergens cause human
      infections. In the USA, an endemic region of this infection, most human cases are
      due to Babesia microti. In Europe, babesiosis is considerably rare and is caused
      by Babesia divergens, with splenectomized patients being at highest risk. The
      spectrum of disease is broad, ranging from an apparently silent infection to a
      fulminant, malaria-like disease. Symptoms include fever, chills and icterus. The
      treatment of choice is clindamycin and quinine. The laboratory diagnosis is based
      on direct detection of the parasite from blood smears. Due to increasing
      international travel, even relatively uncommon parasitic infections can be found
      in the Czech Republic and babesiosis is just one of them.

PMID- 18072300
TI  - [The 43rd autumn meeting of the Japan Radiological Society. Nagoya, Japan.
      October 25-27, 2007. Abstracts].

PMID- 18072301
TI  - Retraction: Zheng Z, Chen B. Effects of Pravastatin on neuroprotection and
      neurogenesis after cerebral ischemia in rats. Neuroscience Bulletin
      2007,23(4):189-197.

PMID- 18072302
TI  - Solubilization and insertion into reverse micelles of the major myelin
      transmembrane proteolipid.
AB  - The Folch-Pi proteolipid has been isolated from bovine white matter and
      characterized with respect to phospholipid and glycolipid composition. The
      protein-lipid complex has been solubilized in aqueous reverse micelles of di(2
      ethylhexyl) sodium sulfosuccinate and isooctane. Solubilization of this otherwise
      water-insoluble proteolipid requires small amounts of water, the percent of
      solubility being maximum for a low molar ratio of water to surfactant (Wo = 5.6).
      Unlike hydrophilic proteins, the extent of incorporation into the micellar system
      is negligible at 50 mM surfactant and reaches 90Vo only at 300 mM. However, the
      conformation of the proteolipid in reverse micelles as studied by fluorescence
      emission spectroscopy and circular dichroism was not affected by variations of
      the surfactant concentration. These results are consistent with the peculiar
      properties of the aqueous environment of the proteolipid within the reverse
      micelles and may reflect the membrane-like character of these bio-assemblies.

PMID- 18072304
TI  - [Abstracts of the 182 Meeting of the Rheinisch-Westfalischen Society of Internal
      Medicine, 22-24 November 2007, Essen].

PMID- 18072303
TI  - Abstracts of the Global Congress of Minimally Invasive Gynecology, 36th Annual
      Meeting of the AAGL, November 13-17, 2007, Washington, DC, USA.

PMID- 18072305
TI  - Angry sentinels and businesslike women: identity and marital status in 1950s
      English library career novels.

PMID- 18072306
TI  - Race in British eugenics.

PMID- 18072307
TI  - Reading South Pacific: colonialism and anthropology in an Australian journal.

PMID- 18072308
TI  - Gender economics in action: rural women's economic citizenship in Finland during
      the twentieth century.

PMID- 18072310
TI  - Reflections on the health social sciences--then and now.
AB  - After its beginnings in the United States, medical sociology started to take hold
      in Germany in 1958 with a conference that resulted in the first book on medical
      sociology published in Germany. From uneasy marginality, the field has grown to
      include disciplines other than sociology--anthropology, economics, and political
      economy. Today, the field might best be called the "health social sciences." The
      main body of work employs the consensual perspective, but work done using a class
      conflict perspective is increasingly significant.

PMID- 18072309
TI  - Race, gender, and national identity in the American and British telephone
      industries.

PMID- 18072311
TI  - Shooting the messenger: the vilification of Irving J. Selikoff.
AB  - Dr. Irving J. Selikoff (1915-1992), a New York physician based at Mount Sinai
      Hospital, was the leading American medical expert on asbestos-related diseases
      between the 1960s and early 1990s. In a country that had been the world's
      greatest consumer of asbestos, he was also at the center of the key controversies
      connected with the mineral. In these controversies, Selikoff was consistently
      demonized as a media zealot who exaggerated the risks of asbestos on the back of
      bogus medical qualifications and flawed science. Since his death, the criticism
      has become even more vituperative and claims have persisted that he was malicious
      or a medical fraud. However, most of the attacks on Selikoff were inspired by the
      asbestos industry or its sympathizers, and for much of his career he was the
      victim of a sustained and orchestrated campaign to discredit him. The most
      serious criticisms usually more accurately describe his detractors than Selikoff
      himself.

PMID- 18072312
TI  - Trends in preterm-related infant mortality by race and ethnicity, United States,
      1999-2004.
AB  - Trends in preterm-related causes of death were examined by maternal race and
      ethnicity. A grouping of preterm-related causes of infant death was created by
      identifying causes that were a direct cause or consequence of preterm birth.
      Cause-of-death categories were considered to be preterm-related when 75 percent
      or more of total infant deaths attributed to that cause were deaths of infants
      born preterm, and the cause was considered to be a direct consequence of preterm
      birth based on a clinical evaluation and review of the literature. In 2004, 36.5
      percent of all infant deaths in the United States were preterm-related, up from
      35.4 percent in 1999. The preterm-related infant mortality rate for non-Hispanic
      black mothers was 3.5 times higher and the rate for Puerto Rican mothers was 75
      percent higher than for non-Hispanic white mothers. The preterm-related infant
      mortality rate for non-Hispanic black mothers was higher than the total infant
      mortality rate for non-Hispanic white, Mexican, and Asian or Pacific Islander
      mothers. The leveling off of the U.S. infant mortality decline since 2000 has
      been attributed in part to an increase in preterm and low-birthweight births.
      Continued tracking of preterm-related causes of infant death will improve our
      understanding of trends in infant mortality in the United States.

PMID- 18072313
TI  - U.S. medical students' knowledge about the military draft, the Geneva
      Conventions, and military medical ethics.
AB  - The objective of this study was to ascertain how much U.S. medical students are
      taught about and know about military medical ethics, the Geneva Conventions, and
      the laws governing conscription of medical personnel. The authors developed an
      Internet-based questionnaire on these matters, and e-mail invitations to
      participate were sent to approximately 5,000 medical students at eight U.S.
      medical schools. Thirty-five percent of e-mail recipients participated in the
      survey. Of those, 94 percent had received less than one hour of instruction about
      military medical ethics and only 3.5 percent were aware of legislation already
      passed making a "doctor's draft" possible; 37 percent knew the conditions under
      which the Geneva Conventions apply; 33.8 percent did not know that the Geneva
      Conventions state that physicians should "treat the sickest first, regardless of
      nationality;" 37 percent did not know that the Geneva Conventions prohibit ever
      threatening or demeaning prisoners or depriving them of food or water; and 33.9
      percent could not state when they would be required to disobey an unethical
      order.

PMID- 18072314
TI  - From Chinese model to U.S. symptoms: the paradox of China's health system.
AB  - This article explains the paradox of China's recent failure to secure significant
      improvements in the health of its people despite once being the envy of the
      developing world for its successful health policies and its huge sustained
      increases in both economic growth and expenditure on health care. The authors
      begin with an outline of the organization and financing of China's health
      services, then track the recent upward trend in health spending and examine its
      structural features in conjunction with those of spending in other, comparable
      countries. The main discussion consists of an evaluation of health service system
      performance in China during the reform era and an explanation of its health
      paradox. The key elements in this account are the waste of resources, the neglect
      of proven health interventions, and the lack of fairness in allocation of medical
      resources--all of which are underpinned by the neoliberal orientation of policy
      in the reform era. The authors conclude with some policy proposals centering on
      the restoration of social justice in the health system. The article draws on
      material previously unavailable in English.

PMID- 18072315
TI  - Post-apartheid challenges: household access and use of health care in South
      Africa.
AB  - Since 1994 the South African government has placed equity at the heart of its
      health policy goals. However, there has as yet been surprisingly little
      assessment of the success of policies in reducing inequity. This article provides
      insights on these issues by applying the Affordability Ladder conceptual
      framework in synthesizing evidence drawn from a series of household surveys and
      studies undertaken between 1992 and 2003. These data suggest that, despite policy
      efforts, inequities in access and utilization between socioeconomic groups
      remain. Underlying challenges include worsening community perceptions of the
      quality of publicly provided care and the influence of insurance status on
      utilization patterns. Further and more detailed evaluation of household-level
      policy impacts requires both improvements in the quality of South African survey
      data, particularly in enhancing consistency in survey design over time, and more
      detailed, focused studies.

PMID- 18072316
TI  - Equity impacts of neoliberal reforms: what should the policy responses be?
AB  - The final article in this special section draws together the lessons learned from
      the ALPS analyses and considers a range of potential policy responses. The
      country case studies highlight that health systems in many low- and middle-income
      countries are failing not only the poor but also other income groups, who are
      faced with wide-ranging barriers to accessing the health care they need. A key
      policy intervention to address these health system failures is that of
      challenging the status quo in relation to the public-private health care mix.
      There is an urgent need to strengthen public health services that have been
      systematically neglected over the past few decades while also regulating the
      worst excesses of the private health sector. Promoting a greater reliance on
      financing mechanisms that are progressive and that strengthen cross-subsidies in
      the overall health system is critical, as is ensuring that available financial
      and human resources are equitably allocated among geographic areas and groups.
      Finally, health system interventions of this nature should be supported by
      broader poverty-reduction strategies. Such interventions to fundamentally change
      ailing health systems are essential to break the vicious cycle of poverty, ill
      health, and (further) impoverishment.

PMID- 18072317
TI  - Corporate colonization of health activism? Irish health advocacy organizations'
      modes of engagement with pharmaceutical corporations.
AB  - This article is based on a study that aimed to shed light on the "cultures of
      action" of Irish health advocacy organizations, and particularly their modes of
      engagement with pharmaceutical corporations. Debates about what some interpret as
      the "corporate colonization" of health activism provide the backdrop for the
      analysis. The empirical dimension of the study involved a survey of 112
      organizations and in-depth study of a small number of organizations that manifest
      diverse modes of engagement with the pharmaceutical industry. The varying modes
      of interaction are plotted along a continuum and characterized as corporatist,
      cautious cooperation, and confrontational. Evidence is presented of a strong and
      growing cultural tendency in Irish health advocacy organizations to frame
      pharmaceutical corporations as allies in their quests for better health. The
      analysis of four constitutive dimensions of organizations' cultures of action can
      reveal the legitimating logics underlying their diverging positions around
      pharmaceutical industry sponsorship. While the research shows that pharmaceutical
      corporations have largely succeeded in defining themselves as a philanthropic
      force and rightful players in Irish health activism, it cautions against a
      simplistic conclusion that this is evidence of corporate colonization.

PMID- 18072318
TI  - Is Australia's national medicines policy failing? The case of COX-2 inhibitors.
AB  - Australia has a National Medicines Policy with aims that include quality use of
      medicines, but policy stakeholders failed to protect Australia from the COX-2
      (cyclo-oxygenase-2) inhibitor disaster. Drug regulators did not warn prescribers
      appropriately about potential cardiovascular risks. The Pharmaceutical Benefits
      Scheme did not limit unjustified drug expenditures on COX-2 inhibitors. Drug
      companies ran intense and misleading promotional campaigns on COX-2 inhibitors
      without adequate controls. Independent drug information was insufficient to
      counter the effects of the millions of dollars spent on advertising. Core
      elements of the National Medicines Policy--in particular the drug approval
      process, the post-marketing surveillance system, the control of drug promotion,
      and the quality of independent drug information--require major reappraisal if we
      want to avoid similar disasters in the future.

PMID- 18072319
TI  - The role of international migration in infectious diseases: the HIV epidemic and
      its trends in Japan.
AB  - Globalization and its associated international migrations facilitate the spread
      of infectious diseases. This article reports trends in and discusses the relation
      between international migration and HIV infection in Japan. The authors analyze
      relevant literature, drawing on government and other sources. Among foreigners in
      Japan, there were 27.0 reported HIV and 9.3 reported AIDS cases per million in
      1990, and 52.9 HIV and 38.8 AIDS cases per million in 2000. These rates were
      initially 45 to 90 times the population prevalence of HIV and AIDS among
      Japanese, but are now only 10 to 20 times the prevalence among Japanese, as HIV
      becomes an increasing problem for the Japanese population. HIV-infected
      foreigners who are uninsured are at a disadvantage for diagnosis, counseling, and
      treatment compared with insured persons, and at a significantly higher risk for
      low CD4 counts. For all sections of Japan's population, counseling and testing
      are inadequate, and surveillance of behavioral risk, infection, and disease is
      limited. International migrants are at increased risk for HIV transmission and at
      a disadvantage for care and treatment. Japan needs both to develop policies that
      assist migrants and to respond to the growing threat among its nonmigrant
      population.

PMID- 18072320
TI  - Cuba's international cooperation in health: an overview.
AB  - In the first years after Cuba's 1959 revolution, the island's new government
      provided international medical assistance to countries affected by natural
      disasters or armed conflicts. Step by step, a more structural complementary
      program for international collaboration was put in place. The relief operations
      after Hurricane Mitch, which struck Central America in 1998, were pivotal. From
      November 1998 onward, the "Integrated Health Program" was the cornerstone of
      Cuba's international cooperation. The intense cooperation with Hugo Chavez's
      Venezuela became another cornerstone. Complementary to the health programs
      abroad, Cuba also set up international programs at home, benefiting tens of
      thousands of foreign patients and disaster victims. In a parallel program,
      medical training is offered to international students in the Latin American
      Medical School in Cuba and, increasingly, also in their home countries. The
      importance and impact of these initiatives, however, cannot and should not be
      analyzed solely in public health terms.

PMID- 18072321
TI  - "Let us live and let them die".
AB  - A WHO staff member's parting salvo to the international health agency and its
      neoliberal approach to health.

PMID- 18072322
TI  - Press report: WHO criticized for neglecting evidence.
AB  - A study published in The Lancet reveals that when developing "evidence-based"
      guidelines, the World Health Organization routinely forgets one key ingredient:
      evidence. The study is based on interviews with senior WHO officials and analyses
      of various guidelines to determine how they were produced. The authors found a
      distinctly non-transparent process.

PMID- 18072323
TI  - Cardiac rehabilitation in Portugal--developments between 1998 and 2004.
AB  - INTRODUCTION: Cardiac rehabilitation (CR) has recognized value in cardiovascular
      disease. However, according to the 1998 survey of the Portuguese Study Group on
      Exercise Pathophysiology and Cardiac Rehabilitation, it was still underused in
      Portugal, with much lower referral rates than other European countries. The aim
      of the present work was to assess developments in CR in Portugal between 1998 and
      2004. METHODS: A form requesting information on general characteristics,
      technical staff, program phases and components, and funding, was sent to all CR
      centers. The rate of referral to CR was calculated by comparing these data with
      official data from hospital discharges for acute coronary syndromes in 2004.
      RESULTS: There was a twofold increase in the number of CR centers, mainly because
      of new public hospitals. The programs are well organized and have actually been
      improved in recent years. The overall admission rate in 2004 was 1.5%, which,
      despite representing an increase compared to 1998, is still much lower than the
      rates of other European countries. Most of the problems previously reported,
      including the size and location of centers, training, funding and educational and
      cultural issues, have not been overcome. CONCLUSION: Although there have been
      some improvements, the number of patients who are referred to CR in Portugal is
      still too low. It is essential to address and to resolve most of the issues that
      are limiting patients' access to this treatment.

PMID- 18072324
TI  - Cardiac involveent in type 1 myotonic dystrophy.
AB  - Myotonic dystrophy is a multisystem disorder in which cardiac involvement is
      common, particularly in conduction tissue. Its severity and symptoms vary, and so
      careful monitoring is required and a permanent pacemaker may need to be
      implanted. The aim of the study was to evaluate cardiac alterations and to
      correlate them with genetic (CTG expansion) and neurological data. Of the 46
      patients studied, 80.4% presented asymptomatic cardiac conduction abnormalities
      but only one had impaired global systolic function, despite 32.6% having changes
      in left ventricular segmental contractility. Left ventricular noncompaction was
      found in 8 patients. Patients with greater CTG expansion had more severe
      neurological involvement and conduction abnormalities, and those with greater
      neurological disability had also more significant conduction tissue involvement.

PMID- 18072325
TI  - Apical ballooning syndrome--a review of five cases.
AB  - INTRODUCTION: Takotsubo syndrome (apical ballooning syndrome) was described for
      the first time in Japan, at the beginning of the 1990s. It is characterized by
      the acute onset of extensive but transient akinesia of the apical and mid
      portions of the left ventricle, in the absence of significant coronary disease.
      OBJECTIVE: We describe five patients who were admitted to our hospital with this
      new syndrome between June 2004 and December 2005. These patients represented 0.8%
      of a total of 613 patients admitted for acute myocardial infarction in that
      period. RESULTS: All the patients were female, with a mean age of 60.2+/-10.3
      years. Chest pain was the most frequent clinical presentation (n=5). A possible
      triggering factor, intense emotional stress, was identified in two patients. At
      admission, the electrocardiogram showed ST elevation in two patients and Q waves
      in the precordial leads in one. All cases had negative T waves in the precordial
      leads at some point. All patients had increased troponin levels but only two had
      elevated cardiac enzymes. The echocardiogram revealed extensive akinesia of the
      apical and mid portions of the left ventricle, and a thrombus was observed in one
      patient. Coronary angiography showed no significant lesions. Currently, all five
      patients are virtually asymptomatic, with regression of left ventricular wall
      motion abnormalities on echocardiography. CONCLUSION: This is the first series of
      apical ballooning syndrome described in Portugal. Although rare, it should be
      considered in the differential diagnosis of acute myocardial infarction. Despite
      its transient nature, in the acute phase it can be a serious condition. More
      research is needed to better characterize this new entity.

PMID- 18072326
TI  - Post-percutaneous coronary angioplasty atheroembolization--a feared iatrogenic
      complication.
AB  - Atheroembolic disease is a rarely recognized clinical entity. The growing use of
      antiplatelet and thrombolytic therapy and of invasive cardiovascular procedures
      in acute coronary syndromes has nevertheless transformed this feared iatrogenic
      complication into an increasingly frequent diagnosis. The authors review this
      entity through the case of a 71-year-old man who, fifteen days after undergoing
      thrombolysis for acute myocardial infarction with ST-segment elevation, followed
      by elective percutaneous coronary revascularization under triple antiplatelet
      therapy, came to the emergency department with a clinical setting of mental
      confusion, gastrointestinal bleeding, oliguria and cutaneous eruptions on the
      lower limbs; laboratory tests revealed severe azotemia and hyperkalemia. With a
      diagnostic hypothesis of systemic atheroembolization, a cutaneous lesion biopsy
      was performed, which confirmed the diagnosis. Supportive treatment led to
      neurological and cutaneous recovery, but the patient developed chronic renal
      failure. The pathophysiology, forms of presentation, treatment and prognosis of
      atheroembolic disease are discussed, highlighting the importance of a high degree
      of clinical suspicion for diagnosis.

PMID- 18072327
TI  - Heart disease in pregnancy.

PMID- 18072328
TI  - [ACC/AHA/ESC 2006 guidelines for the management of patients with ventricular
      arrhythmias and the prevention of sudden cardiac death--executive summary].

PMID- 18072329
TI  - Right ventricular dilatation during exercise. A new sign?

PMID- 18072330
TI  - [Echocardiography and the Portugueses: the euroecho 11 and the European
      accreditation test].

PMID- 18072331
TI  - ["Utilization of antihypertensive agents in Continental Portugal"].

PMID- 18072332
TI  - Nonlinear analysis of brain magnetoencephalographic activity in alzheimer disease
      patients.

PMID- 18072333
TI  - Microglia in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is a neurodegenerative disorder that results in the
      selective death of motor neurons in the central nervous system. This progressive
      motor neuron degeneration leads to death of the patient on average three to five
      years after onset of the disease. To date, no therapy is available. Many
      hypotheses have been formulated to explain the selective degeneration of motor
      neurons. One of the most studied hypotheses is the putative role of the
      inflammatory response that accompanies motor neuron death. The proliferation of
      microglia and astrocytes has been considered to be a secondary phenomenon, but
      recently, evidence is accumulating in favour of a contributory role of the non
      neuronal cell populations to the pathogenesis of the disease. In this review, we
      will introduce the characteristics of microglial cells in the central nervous
      system. We will summarize the evidence of the expansion and the activation of the
      microglial cell population that accompanies motor neuron degeneration. Finally,
      an overview will be given of the different therapeutic strategies that targeted
      the inflammatory process in amyotrophic lateral sclerosis.

PMID- 18072334
TI  - EEG source localization of the epileptogenic focus in patients with refractory
      temporal lobe epilepsy, dipole modelling revisited.
AB  - EEG source localization of epileptic brain activity is of diagnostic importance
      in the presurgical evaluation in patients with refractory epilepsy. Localization
      of the epileptogenic foci by visual inspection of the scalp EEG only is a
      qualitative and subjective procedure and may be difficult. Techniques such as
      dipole modelling allow to analyse the characteristics of the generators of the
      electric activity inside the brain in a quantitative and objective way.
      Interictal and ictal dipole modelling reveal different types of spike voltage
      fields and dipole sources. The published literature shows conflicting evidence in
      different study populations in terms of results and reliability of localization.
      The reliability of dipole models has been questioned, especially in case of deep
      mesial temporal lobe sources. In order to validate dipole modelling, comparisons
      between dipole localizations and intracerebral fields, recorded with depth
      electrodes, were made. When interpreting results of dipole modelling, the
      intrinsic limitations of this technique should be taken into account.

PMID- 18072336
TI  - The prevalence and characteristics of migraine among the Belgian working
      population.
AB  - INTRODUCTION: Migraine is a very common disease. For the first time in Belgium, a
      study has been set up to assess some characteristics of the migraine problem like
      occurrence, frequency, duration, in a convenience sample of employees. METHODS
      AND STUDY POPULATION: A total of 1660 persons participated in the study.
      Employees completed a short international validated self-administered
      questionnaire (ID-Migraine Screener) in which migraine-related characteristics
      have been assessed. RESULTS AND DISCUSSION: Lifetime prevalence of migraine in
      this study was 20.2% (95% CI: 18.3-22.2%), was significantly higher for women
      than for men and was the highest in the age group 35-44 years. On average 10.6
      lost working days due to migraine were reported per absentee and per year, or per
      migraineur on average 2.3 days, and per employee 0.4 days. Migraine is estimated
      to account for about 1,154,336 lost working days each year in Flanders and
      Brussels. However underreporting of symptoms, attacks and sick leave days was
      estimated at about 50%, depending on the time frame. Sixty-nine percent of the
      migraine sufferers use medication regularly. Only minor differences have been
      detected in migraine prevalence according to the recorded occupational risks.
      Finally, the limitations of the study are discussed.

PMID- 18072335
TI  - The aerobic forearm exercise test, a non-invasive tool to screen for
      mitochondrial disorders.
AB  - The diagnosis of a mitochondrial disorder is often difficult. Therefore, new
      approaches and diagnostic criteria are being developed. One of these tests is the
      aerobic forearm exercise test, a screening tool that can contribute to assess
      whether or not the patient suffers from a mitochondrial myopathy. With this
      simple, non-invasive test, the oxidative metabolism of muscle can be evaluated in
      rest and during exercise. We performed the aerobic forearm exercise test in
      patients with a mitochondrial disorder and an identified pathogenic gene
      mutation, in patients with a suspected mitochondrial disorder based on their
      clinical presentation and biochemical results, but without a molecular diagnosis,
      and in patients with atypical fatigue and no characteristics of a mitochondrial
      myopathy. In the first two groups, abnormal oxygen extraction from the blood
      during exercise was observed in four out of twelve patients. In the third group
      no abnormalities were found. The number of patients that we could test so far was
      limited, but all the patients experienced the aerobic forearm exercise as an easy
      test. We would like to stimulate clinicians to perform this test whenever a
      mitochondrial myopathy is suspected, as it can be a valuable diagnostic screening
      tool.

PMID- 18072337
TI  - A carotid artery dissection presenting with dysphagia due to a dilation of upper
      oesophagus.
AB  - Carotid and vertebral artery dissection is one of the major causes of ischemic
      stroke in young patients and diagnosing it remains a challenge for the clinician
      due to its variable clinical presentation. We report the case of a 57-years old
      man admitted to the emergency department complaining of dysphagia and a hoarse
      voice. Physical examination revealed a left deviation of his tong and some
      weakness of the left side of his soft palate. A gastroscopy and a cervical
      tomodensitometry revealed the presence of an important dilation of his upper
      oesophagus. A cerebral magnetic resonance was performed, showing en excentric
      high signal intensity on the left carotid artery, and the MR angiography
      confirmed the presence of an acute dissection on the left internal carotid
      artery. Our patient suffered of a left carotid artery dissection presenting with
      ipsilateral Xth and XIIth nerve palsies. His main symptom was a dysphagia due to
      a dilation of his upper oesophagus; the pneumogastric nerve being responsible for
      the parasympathic innervation of the upper muscles of the oesophagus.

PMID- 18072338
TI  - Obsessive-compulsive disorder secondary to a right parietal lobe haemorrhage: a
      case report.
AB  - This case report presents a 39-year-old previously healthy man, who presented
      with typical obsessive-compulsive disorder and neurological symptoms and was
      found to have a right parietal lobe haemorrhage. His psychiatric and neurological
      recovery was associated with a complete radiological resolution. This report is
      consistent with recent imaging studies implicating the parietal lobe in the
      pathogenesis of obsessive-compulsive disorder and adds haemorrhage to the list of
      organic cerebral lesions causally associated with this disorder.

PMID- 18072339
TI  - A massive extradural cerebrospinal fluid collection.

PMID- 18072340
TI  - [Drug-induced liver disease].

PMID- 18072341
TI  - [Drug-induced disturbances in endocrine, metabolism, and water and electrolyte
      metabolism].

PMID- 18072342
TI  - [Side effects and proper usage of anxiolytics].

PMID- 18072343
TI  - [Adverse effects of leukotriene-antagonists].

PMID- 18072344
TI  - [Adverse effects of thromboxane receptor antagonists and synthase inhibitors].

PMID- 18072345
TI  - [Stevens-Johnson syndrome/toxic epidermal necrolysis].

PMID- 18072346
TI  - [Drug-induced parkinsonism].

PMID- 18072347
TI  - [Drug-induced pulmonary edema].

PMID- 18072348
TI  - [Drug-induced rhabdomyolysis].

PMID- 18072350
TI  - [The 25th Hokkaido Conference of Thyroid Disease].

PMID- 18072349
TI  - [The 32th meeting of the Hokkaido Society for Rheumatology].

PMID- 18072351
TI  - From trees to wood and back: perspective on clinical data analysis in thoracic
      surgery.
AB  - General thoracic surgery has been slow to embrace advanced statistical techniques
      to assess outcome and direct future therapy to individual patients (the "trees")
      based on aggregating data and discovering informative patterns in them (the
      "wood"). This is due in part to the nature and complexity of the practice.
      However, methods exist that deal with problems of small numbers, variable case
      volume, and heterogeneity of patients, diseases, and therapies. For effective
      analysis of these multiple variables, modern strategies must be used and pitfalls
      avoided. For generating new knowledge about appropriateness of therapy, the focus
      of analyses must include long-term outcome. Quality improvement efforts may be
      assisted by in-depth analysis of short-term outcome from a select number of
      centers to inform future universal efforts. Ultimately, these results need to
      feed back to improved management of the individual patient.

PMID- 18072352
TI  - Predictive ability of preoperative indices for major pulmonary surgery.
AB  - In the last years a number of significant improvements have been achieved in risk
      stratification for lung cancer patients who undergo lung resection. Nevertheless,
      future improvements should be based in prospective cooperative studies including
      a large number of comparable cases. First limitations of available published
      evidence come from the fact that FEV1 and ppo-FEV1 are pivotal in patient
      classification. Besides, ppoFEV1 is not a reliable predictor of complications in
      patients with COPD, since their functional behavior is different compared with
      non-COPD patients after lung resection and, although current calculation methods
      may be accurate in estimating the residual definitive FEVI at 3 to 6 months after
      surgery, they tend to overestimate the actual FEV1 in the first postoperative
      days, when most of the complications occur. The assumption that FEV1 and DLCO are
      highly correlated is the reason why ppoDLCO estimation is not recommended in all
      patients, limiting the predictive ability of this test. Finally, the predictive
      ability of exercise testing has not been proven since it is not systematically
      recommended in all patients before lung resection.

PMID- 18072353
TI  - Predictive ability of preoperative indices for esophagectomy.
AB  - Esophageal resection remains the mainstay of treatment for early-stage cancer. In
      spite of recent advances, these mortality rates remain significant when compared
      with other major surgical procedures. Several risk scores have been reported, but
      few have been put to the test with adequate and objective validation studies in
      high volume centers. Others already in use have poor discriminatory power.

PMID- 18072354
TI  - The rationale for developing scoring systems for clinical practice.
AB  - Risk scoring systems are used infrequently in thoracic surgery. Current systems
      accurately predict infrequent complications such as operative mortality, but most
      systems have not been evaluated adequately for prediction of nonfatal
      complications. The extant systems are well suited to risk stratification in large
      patient populations. However, they have not yet reached the degree of refinement
      that enables accurate prediction for individual patients. Efforts at improving
      clinical and biological predictive systems for postoperative complications are
      important in improving patient selection for surgery, enhancing informed consent
      processes, stratifying patient groups for research and internal audit, and
      appropriately assigning resources for postoperative management.

PMID- 18072355
TI  - The European societies subjective and objective scores.
AB  - This article explores the issue of risk modeling for patients undergoing lung
      resection. The development of risk stratification in thoracic surgery is
      discussed together with its application in patient populations and in individual
      patients. The European Societies Risk Scores (Objective and Subjective) Version 1
      are discussed in detail. The development of Version 2 of the risk score is
      described, and the future role of risk scoring on thoracic surgical practice is
      considered.

PMID- 18072356
TI  - Neural networks and artificial intelligence in thoracic surgery.
AB  - The human brain has billions of neurons and connections that cannot be emulated
      by computers. This structure could explain the anatomical basis of typically
      human psychological activities like intuition or artistic creation. On the other
      hand, the computer-organized way of "reasoning" binary problems through
      systematic comparison of a large number of data-as AIM does--is impossible to be
      emulated by humans. At the same time, AIM, through the use of different methods
      like ANN or DM systems, is able to give individualized answers to otherwise
      probabilistic population problems. Hence, that is the reason for its application
      in the assessment of surgical risk in lung resection candidates. With regard to
      AIM methodology, many issues could be addressed and argued, especially on the
      data collection because of the retrospective nature of the data on which the
      available contributions from the literature are based. In the larger studies,
      patients from different centers treated by different surgical teams were
      included. Both circumstances could have caused heterogeneity of the study groups,
      which, in turn, can lead to less-reliable conclusions. Even if limited, our
      experience became an appealing one because AIM seems to be a potentially useful
      complementary tool to the nonreplaceable clinical judgment.

PMID- 18072357
TI  - Clinical and nonclinical indicators of performance in thoracic surgery.
AB  - One of the most important steps in the entire process of monitoring and improving
      quality of care is to identify the proper quality measures. This may be
      challenging from the outset since no single indicator can fully comprehend the
      entire concept of quality of care, which is multidimensional by nature. Ideally,
      multiple indicators should be used at the same time to obtain a more precise
      assessment of the quality of care. The quality of care can be measured by
      observing its structure, its processes, and its outcomes. Each indicator may
      reflect different aspects of quality and may be of particular interest to
      different audiences (providers, consumers, regulators, purchasers). The selection
      of one or the other may depend on the objectives of the analysis and the target
      audience. Although outcomes represent the ultimate product of health care, if the
      focus is on identifying and remedying apparent variations in performance, it is
      often preferable to measure not only outcomes but also the desirable processes of
      care. From a performance management perspective, the key issue is that a
      desirable process should be unambiguously associated with improved patient health
      outcomes. Monitoring the process can then be a substitute for measuring the
      outcome. Unlike outcome indicators, process measures have the potential to
      identify for clinicians exactly which processes they followed or did not follow
      that had the potential to affect patient outcomes. Process indicators provide
      information that is actionable. Finally, thoracic surgeons should take the lead
      in the managerial approach to the evaluation of performance, preventing
      administrative personnel unfamiliar with our multifaceted clinical world from
      judging our practice through imprecise instruments. We, as physicians, must
      absolutely improve our skill and confidence in risk analysis, outcome-evaluation
      methods, and process-based assessment of our practice.

PMID- 18072358
TI  - Audit, quality control, and performance in thoracic surgery: a North American
      perspective.
AB  - Although difficult to precisely define, health care quality is often measured by
      components of structure, outcomes, and process. One way for thoracic surgeons to
      evaluate their practices is to compare themselves with evidence-based national
      guidelines. Outcomes data are often generated from entries into large patient
      databases. The largest examples of these databases include the STS National
      Databases and the VA/ACS NSQIP programs. Each of these has unique features, but
      there is the common goal of enabling participants to examine their surgical
      outcomes and results relative to others. The data integrity of these databases is
      high. The new STS composite quality score for CABG combines providers' outcome
      and practice data into a calculated index for comparison with national averages.
      In addition to providing meaningful information regarding surgical outcomes and
      quality, these databases are used as the basis for risk-adjusted models to
      accurately predict surgical morbidity and mortality. These models can be used as
      auditing tools against which surgeon- and site-specific morbidity and mortality
      can be compared with predicted values. As practices and methods continue to
      evolve, measures of quality--and therefore quality itself--will continue to
      improve, resulting in better patient care.

PMID- 18072359
TI  - Audit, quality control, and performance in thoracic surgery--a European
      perspective.
AB  - The internal audit process is preparatory to independent, external quality
      control assessment. The current status of quality control implementation in
      European thoracic surgery comprises existing and functioning but uncoordinated
      resources. There is a need to coordinate these resources to achieve a consistent
      external audit process.

PMID- 18072360
TI  - Thoracic surgery certification in the United States of America.
AB  - As we enter the 21st century, thoracic surgeons can look back with pride and
      gratitude to their predecessors who placed a high premium on clinical practice
      and certification. Thoracic surgery, however, is dynamic, not static. So, too,
      should be thoracic surgery recertification. In recent years, considerable effort
      has been expended to move thoracic surgery recertification from a 10-year
      reexamination cycle to a dynamic, multiyear cycle in an effort to ensure the
      public that board-certified thoracic surgeons remain current with evolving
      knowledge and technology. It is in this milieu that Maintenance of Certification
      (American Board of Medical Specialties, Evanston, Illinois) has evolved.

PMID- 18072361
TI  - Towards establishing standards of practice in general thoracic surgery: the
      European perspective.
AB  - The European situation makes it not easy to establish uniform conditions for
      quality assurance in GTS. However, by setting up the necessary tools in the form
      of the European Board, the European Cardiovascular and Thoracic Surgery Institute
      of Accreditation, and the European Registry, the two major scientific societies
      of Europe have prepared the necessary requirements for that quality assurance
      [6]. All these instruments and the application of the suggested mechanisms
      currently are still voluntary; nevertheless, it is important that regulations are
      defined within the concerned scientific societies and not imposed from an outside
      legal body. It lies in the interest and in the discretion the individual
      departments and surgeons to use and to comply with these existing possibilities
      to perform GTS at a uniform European quality level.

PMID- 18072362
TI  - Toward public disclosure of surgical results: experience of cardiac surgery in
      the United Kingdom.
AB  - Public disclosure of surgical results has been implemented in recent years. This
      article discusses the disclosure of cardiac surgery results in the United
      Kingdom.

PMID- 18072363
TI  - The comparison of performance between thoracic surgical units.
AB  - Managed care systems demand an increased effort in quality monitoring and
      improvement processes through the analysis of performance of health care
      providers. The performance can be assessed by analyzing the outcomes or the
      clinical processes. To date, outcome indicators are still the most widely used
      quality end points in our specialty. However, because patients are not randomly
      allocated to different physicians or hospitals, different case-mixes at different
      institutions may make the comparison of crude outcome rates misleading.
      Therefore, the selection of quality end points must account for the differences
      in the prevalence of risk factors, and clinical risk modeling must become the
      logical and necessary approach for provider profiling to prevent inappropriate
      clinical and administrative decisions and unethical risk-averse behaviors.
      Regression analyses are the analytic techniques most commonly used for risk
      modeling. However, the resultant models are useful only if they reliably predict
      outcomes for patients by determining significant risk factors associated with the
      outcome of interest. Recent evidence has shown that bootstrap resampling analysis
      can formalize the development of model building, removing much of the human
      biases associated with regression analysis, providing a balance between selecting
      risk factors that are not reliable (type I error) and overlooking variables that
      are reliable (type II error), and introducing a concrete measure of reliability
      of the risk factors. Regardless of the type of end point that will be used in the
      future for quality management purposes. data collection will always be of
      paramount importance. The costs for implementing and managing international
      multicentric databases (such as the European Thoracic Surgery Database or the STS
      Thoracic database) seem, therefore, justified by the benefits that could be
      derived from the quality improvement processes, which will be based on them.

PMID- 18072364
TI  - Performance-related pay for hospital consultants.
AB  - In the United Kingdom there about 300,000 people who earn at least pounds 100,000
      per year. These people represent just 1% of U.K. workers. Hospital consultants
      are in this exclusive earning group, and so they should be. Following a new pay
      deal in 2003, which enabled consultants to achieve a record average NHS salary of
      pounds 110,000 in 2006, there is growing momentum to introduce a system of
      performance-related pay. Such a system could work. Many believe this would create
      the necessary leverage to get the consultant body to work with the managers to
      create a robust NHS that is fit for purpose and can compete healthily against
      alternative providers in an open marketplace. The resolve to achieve this has
      never been stronger. The NHS has always been dogged by status and power divides
      between the different groups of workers. The time has come to make some headway
      with breaking down these divides and get on with running a business. Let's hope
      the NHS can transform into a place where managers and doctors trust each other
      and work better together. This would give the 1.3 million people that work in the
      NHS the best chance of creating a successful business that cares for ill people.
      The financial and professional rewards will follow.

PMID- 18072365
TI  - Pay for performance in thoracic surgery.
AB  - In the context of improving the quality of the medical practice, PFP programs
      have been developed to reward best medical practice. Early studies showed little
      gain in quality after implementing PFP family practice programs and some
      unintended consequences, like excluding high-risk patients from medical services
      when good outcomes were linked to payment. To date, no PFP programs have been
      implemented in surgical practice, but it is expected that value-based purchasing
      philosophy will be extended to surgical specialties in the near future. Quality
      initiatives in surgery can be based on outcome or process measures. Outcomes
      focused quality approaches rely on accurate information obtained from
      multiinstitutional clinical databases for calculation of risk-adjusted models.
      Primary outcomes such surgical mortality are uncommon in modern thoracic surgery
      and outcome measures should rely on more prevalent intermediate outcomes such as
      specific postoperative morbidities or emergency readmission. Process-based
      quality approaches need to be based on scientific evidence linking process to
      outcomes. It is our responsibility to develop practice guidelines or
      international practice consensus to facilitate the parameters to be evaluated in
      the near future.

PMID- 18072366
TI  - Lifestyle risk factors for chronic disease in a multiethnic population: an
      analysis of two prospective studies over a 20-year period.
AB  - OBJECTIVE: This study investigated changes in risk factors in Hawaii over 20
      years and compared health behaviors among ethnic groups with well-documented
      differences in disease risk. DESIGN: Comparison of scores of a Chronic Disease
      Risk Index (CDRI) in the population of two large population-based cohorts.
      PARTICIPANTS: The respective sample sizes for the two cohorts were 19,319 and
      97,746 persons ages > or = 40 years of White, Chinese, Filipino, Japanese, and
      Native Hawaiian ancestry. MAIN OUTCOME MEASURES: The CDRI included smoking
      status, alcohol use, meat intake, fruit and vegetable consumption, and body mass
      index. Mean total and component scores were compared over time and by ethnic
      group after adjustment for age and education. RESULTS: We found a reduction in
      overall CDRI scores, ie, improved health profiles, for both men and women over
      time. Men, Native Hawaiians, and Whites had higher CDRI scores than women and
      Japanese, Chinese, and Filipinos due to their higher scores for smoking, alcohol
      use, and overweight, whereas nutritional intakes were similar in all ethnic
      categories. Smoking, alcohol use, and overweight increased over time in both men
      and women, whereas dietary composition appeared to improve. CONCLUSIONS: This
      analysis suggests an overall reduction in modifiable dietary and lifestyle risk
      factors in Hawaii over time. Persistent differences by sex and ethnic category
      indicate that interventions to modify lifestyle factors need to tailor messages
      to the groups at highest risk.

PMID- 18072367
TI  - Characteristics of insufficiently active hypertensive Black women who volunteer
      to be in a physical activity promotion intervention: an application of social
      cognitive theory and the transtheoretical model.
AB  - BACKGROUND: Hypertension is a significant public health problem for Black
      American women. Increasing physical activity is an effective way to manage
      hypertension. However, Black women are among the least physically active
      racial/ethnic/gender group. In this paper we identify the positive resources and
      areas of need among insufficiently active Black hypertensive women who presented
      to a study to increase their level of physical activity. METHODS: Women completed
      questionnaires to assess self-efficacy to overcome barriers to physical activity,
      confidence to use self-motivation to engage in behaviors supportive of a
      physically active lifestyle, friend and family social support for physical
      activity, and behavioral and cognitive strategies associated with physical
      activity. RESULTS: Sixty-one insufficiently active Black hypertensive women
      participated in the study. The mean age of the sample was 50.48+/-4.2 years. The
      mean body mass index was 35.97+/-6.88 kg/m2. Resting blood pressure was
      133.28/78.21+/-16.41/8.96 mm Hg. According to the Transtheoretical Model stages
      of change, 88.52% of the sample was in contemplation. Women reported a moderate
      level of confidence to overcome barriers, a moderate level of confidence to use
      self-motivation, and reported that barriers rarely interfered with their ability
      to be physically active. However, women had little friend or family support for
      physical activity and only rarely used behavioral strategies to encourage their
      activity. CONCLUSION: To further support this population, physical activity
      interventions should focus on developing social support networks and teaching a
      variety of behavioral strategies important to the adoption of an active
      lifestyle.

PMID- 18072368
TI  - A pilot study of self-management in African Americans with common chronic
      conditions.
AB  - OBJECTIVE: Self-management as a tool to manage chronic conditions has been well
      described for majority populations. Limited studies exist on the potential
      benefit of self-management programs for African Americans with chronic
      conditions. The purpose was to demonstrate the feasibility, effectiveness and
      acceptability of a structured self-management program in African Americans with
      one or more chronic conditions. METHODS: This pilot study involved an
      intervention-only arm of a six-week peer-led program aimed at improving important
      self-management skills, including self-efficacy and physical activity.
      Participants were recruited from local churches and independent living senior
      centers, and trained lay leaders served as facilitators of the self-management
      program. RESULTS: A total of 46 people participated in this program. Participants
      were mostly African American (96%), female (91%), with a mean age of 65 (11), and
      2.7 (1.5) chronic conditions. We found significant increases in pre- to
      postintervention self-efficacy (P<.01) and self-reported walking for exercise
      (P<0.05). Self-rated health also had significant improvement (P<.01). Qualitative
      feedback revealed a desire for more support with transforming traditional foods
      and creative exercise strategies. CONCLUSIONS: A standardized peer-led self
      management course was effective at improving self-efficacy, walking for exercise
      and self-rated health in African Americans with a variety of common chronic
      conditions. Future self-management interventions should focus more on cultural
      interests and strengths such as spirituality, existing support networks for
      behavioral change, and retention strategies to achieve long-term lifestyle
      changes.

PMID- 18072369
TI  - Concordance between self-reported heights and weights and current and ideal body
      images in young adult African American men and women.
AB  - Satisfaction with overweight and obesity purportedly contribute to greater weight
      gain in African American women than men, yet relatively little data on perceived
      (PBI) and ideal body image (IBI) are available for young adult African Americans.
      In this survey, 509 self-identified African American freshmen in 2003 and 669 in
      2006 at a historically Black university completed a survey that included self
      reported height, weight and IBI. In 2003 and 2006, 42.2%-48.8% of men and women
      were overweight (body mass index [BMI] 25.0-29.9 kg/m2) or obese (BMI > or = 30).
      In both surveys, >75% of overweight women and >90% obese women selected a smaller
      IBI. In contrast, a greater proportion of overweight men was satisfied
      (approximately 50%) than the proportion who had larger than IBI (<40%). Among
      students with a normal BMI (<25), men were more likely than women to report being
      smaller than ideal (>45% vs <26%). However, overweight women were more likely
      than overweight men to select a normal PBI (48.5% vs 36.0%). The data in African
      American college freshman do not suggest that greater weight gain in women than
      men is driven by a desire to be heavier. The high proportion of overweight women
      with a normal PBI may contribute to greater weight gain. Of concern, nearly half
      of men with normal BMI want to be heavier, while approximately 5/8 of overweight
      men are satisfied with being overweight or want to be heavier.

PMID- 18072370
TI  - Self identity through Ho'oponopono as adjunctive therapy for hypertension
      management.
AB  - OBJECTIVE: Self Identity through Ho'oponopono is a step-by-step problem-solving
      approach to identify and relieve stress. The objective of this study was to
      determine if Self Identity through Ho'oponopono along with standard medical
      therapy might better control hypertension than standard therapy alone. DESIGN,
      SETTING, PARTICIPANTS: Twenty-three Asian, Hawaiian, and other Pacific Islanders
      from a local community in Hawaii participated in a longitudinal design comparing
      pre- and post-intervention measures of blood pressure. INTERVENTION: Participants
      attended a half-day class on Self Identity through Ho'oponopono to learn ways to
      create balance and correct stress through an understanding of their own self
      identity. Participants learned processes to care for themselves through
      repentance, forgiveness, and transmutation and how to apply the processes in
      their daily lives. MAIN OUTCOME MEASURES: Repeated blood pressure measurements
      were compared before and after the intervention using generalized estimating
      equations; two spirituality questionnaires were administered before and after the
      intervention and analyzed with paired RESULTS: Systolic blood pressure decreased
      after the intervention, averaging 11.86 mm Hg below pre-intervention levels.
      Diastolic blood pressure decreased by 5.44 mm Hg. Spirituality scores
      significantly increased after the intervention. CONCLUSIONS: Self Identity
      through Ho'oponopono was associated with a statistically and clinically
      significant reduction in mean blood pressure. Spirituality scores increased after
      the intervention. We conclude that Self Identity through Ho'oponopono may be an
      effective adjunctive therapy for hypertension. Further research is needed to
      validate these preliminary findings.

PMID- 18072371
TI  - Racial differences in physical activity associations among primary care patients.
AB  - OBJECTIVES: To examine the contributions of self-efficacy, outcome expectations,
      barriers, and demographic/health factors to physical activity behavior in primary
      care outpatients and to determine differences in these associations for African
      American versus Caucasian patients. DESIGN: Cross-sectional, structured
      interview. PARTICIPANTS AND SETTING: Adult internal medicine outpatients (n=393,
      response rate 88.5%) were enrolled. Most were female (70%) and Caucasian (62%)
      with a yearly household income <$20,000 (54%) and history of arthritis (57%).
      Mean age was 48.9+/-11.8 years and BMI was 30.9+/-8.16 kg/m2. MEASUREMENTS: A 30
      minute structured interview assessed self-reported leisure-time physical
      activity, self-efficacy, outcome expectations, perceived barriers, and
      demographic/ health covariates. RESULTS: Based on path analysis, social cognitive
      constructs accounted for 28% of the variance in physical activity in African
      American patients and 25% in Caucasian patients. After controlling for selected
      covariates, path analysis showed a direct association between self-efficacy and
      physical activity for African American (beta=.45, P<.01) and Caucasian patients
      (beta=.34, P<.01). Although higher self-efficacy was associated with higher
      outcome expectations for both groups (beta=.25, P<.05, beta=.21, P<.05,
      respectively), no direct association was found for outcome expectations with
      activity. Self-efficacy demonstrated an indirect association with activity
      through perceived barriers for Caucasian patients only. CONCLUSIONS: Self
      efficacy and perceived barriers were the most important independent correlates of
      physical activity with potential racial differences warranting further study
      noted.

PMID- 18072372
TI  - Health-promoting behaviors and health locus of control from a multicultural
      perspective.
AB  - OBJECTIVES: To assess the relationships between health-promoting behaviors and
      health locus of control (HLC) in the context of cultural differences between
      Jewish and Arab Israelis. METHODS: A random, population-based sample of 358 Jews
      and 162 Arabs, aged 50-75 years, participated in a telephone survey.
      Questionnaires included demographic variables and details on three health
      behaviors, namely balanced nutrition, physical activity and regular checkups, and
      HLC. RESULTS: Arab respondents, especially Arab women, reported lower internal
      HLC and lower engagement in physical activity, while external HLC, balanced
      nutrition, and attending regular checkups varied by ethnicity only. According to
      multiple regression analyses, Jewish ethnicity and male sex were significantly
      related to internal HLC, while Arab ethnicity, older age and lower education were
      significantly related to external HLC. Although internal and external HLC were
      significantly correlated with balanced nutrition and regular physical activity,
      the regression analysis revealed that only higher internal HLC explained the
      variance of balanced nutrition. The variance of all health-promoting behaviors
      was explained by ethnicity, while physical activity was also explained by sex,
      and balanced nutrition was explained by higher economic status and higher
      religiosity. Regular medical checkups were also explained by higher economic
      status. CONCLUSIONS: Health-promoting behaviors and HLC were each mainly related
      to ethnicity and sex. Messages to enhance health-promoting behaviors should be
      adjusted culturally, especially for women.

PMID- 18072373
TI  - Acculturation, weight, and weight-related behaviors among Mexican Americans in
      the United States.
AB  - OBJECTIVE: This analysis explores the association between acculturation and body
      weight, self-perceptions of weight, and attempt to lose weight among Mexican
      Americans. METHODS: Data were analyzed from the National Health and Nutrition
      Examination Survey (NHANES) for 2001-2002. Indicator of acculturation used was
      language assimilation. Factor analysis was used to construct the acculturation
      measure, and descriptive and multivariable analyses were conducted using SUDAAN.
      RESULTS: The acculturation measure differentiated body weight, weight-related
      behavior, and self-perceptions about weight. Those lower on the acculturation
      scale were less likely to have a high BMI (> or =30) (24% vs 32%), and their
      perceptions of their own weight, desired weight, and recent history of trying to
      lose weight differed significantly from those persons high on the acculturation
      scale and these varied by sex. Among Mexican Americans with a BMI > or =25, those
      lower on the acculturation measure were significantly less likely to perceive
      themselves as overweight (60% vs 73%). They were also less likely to have
      attempted to lose weight in the past year than those who were high on the
      acculturation measure (OR = 0.49; 95% CI: 0.31-0.79). CONCLUSIONS: Less
      acculturated Mexican Americans with BMI > or =25 were less likely to perceive
      themselves as overweight and to have tried to lose weight. The acculturation
      measure provides insights into Mexican Americans' perceptions of their own weight
      and their recent attempt of trying to lose weight.

PMID- 18072374
TI  - Healthcare attitudes and behaviors of immigrant and US-born women in Hamtramck,
      Michigan: a MetroNet study.
AB  - OBJECTIVE: Recognizing recent immigrant migration into Hamtramck, Michigan, our
      objective was to conduct a survey focused on female patients seeking health care
      in an ethically diverse primary care clinic. DESIGN: Cross-sectional exploratory
      questionnaire survey study. SETTING: A family medicine center (FMC) in Hamtramck,
      Michigan. PARTICIPANTS: A convenience sample of women patients, age > or =18
      years of age who understood English and/or written or spoken Bangla. MAIN OUTCOME
      MEASURES: Health-seeking behaviors and satisfaction with the US healthcare
      system. RESULTS: 156 women patients participated. Sixty-seven (43%) were
      immigrants, primarily representing three ethnicities: Bangladeshi (61%), Yemeni
      (19%) and Bosnian (13%). The mean length of residence in the United States was
      eight years. Compared with US-born, the immigrants were more likely to report a
      household income of less than $15,000; however they had similar rates of health
      insurance. US-born women reported less satisfaction with our healthcare system.
      Immigrants were more likely to visit their physician when feeling ill, and to
      bring a friend or relative to help alleviate communication problems. Immigrant
      women were also more likely to express a desire for a physician who was female
      and/ or from a similar cultural background. CONCLUSIONS: The study findings
      suggest the need for physicians to be culturally sensitive to the particular
      needs of the immigrant female population they serve and to treat each patient
      within the context of her environment.

PMID- 18072375
TI  - Lifestyle risk factors for chronic disease across family origin among adults in
      multiethnic, low-income, urban neighborhoods.
AB  - OBJECTIVES: To describe the prevalence and co-occurrence of lifestyle risk
      factors for chronic disease by family origin. DESIGN: Cross-sectional analysis.
      SETTING: Multiethnic, low-income, urban neighborhoods in Montreal, Canada.
      PARTICIPANTS: 2033 adults (42.2% male), mean age 39.7 (standard deviation 6.4)
      years OUTCOME MEASURES: Smoking, level of physical activity, dietary habits, body
      mass index. METHODS: Subjects completed self-report questionnaires on
      sociodemographic characteristics, height, weight, and lifestyle behaviors. We
      tested family origin (based on language first learned in childhood and country of
      birth) as an independent correlate of co-occurrence (having at least two
      lifestyle risk factors) in multivariate logistic regression analyses. RESULTS:
      The prevalence of smoking and poor diet was highest among participants of French
      Canadian family origin. Although physical inactivity was uniformly high across
      family origins, it was highest among participants of Portuguese, Italian, and
      Haitian family origin. Obesity was highest among Europeans. The prevalence of
      smoking was lowest among Haitians; poor diet was lowest among South Asians; and
      physical inactivity was lowest among Eastern Europeans. Obesity was lowest among
      Asians, with the exception that 55.9% of South Asians were overweight or obese.
      Relative to French Canadians, adults in all other family-origin groups had a
      lower risk of co-occurrence of lifestyle risk factors. Adults of Asian family
      origin had the lowest prevalence of co-occurrence of lifestyle risk factors.
      CONCLUSION: Variation in the distribution of lifestyle risk factors may explain
      in part differences in chronic disease morbidity and mortality across ethnic
      groups. Prevention programs should take differential distribution of lifestyle
      risk factors by ethnicity into account.

PMID- 18072377
TI  - Peripheral arterial disease in a multiethnic national sample: the role of
      conventional risk factors and allostatic load.
AB  - BACKGROUND: Limited data exist on the prevalence of peripheral arterial disease
      (PAD) among ethnically diverse populations. Our objectives were to assess the
      prevalence of PAD in a multiethnic national sample and examine risk factor
      control and allostatic load (a marker of dysregulation of the inflammatory,
      metabolic, and cardiovascular systems) by race/ethnicity among individuals with
      PAD. METHODS: We analyzed data from the 1999-2002 National Health and Nutrition
      Examination Survey for individuals aged > or =40 with a measured ankle brachial
      index (N=5,083). PAD was defined as an ankle brachial index <0.9. We performed
      bivariate and multivariate analyses to describe the association of race/ethnicity
      with PAD, controlling for sociodemographic factors, clinical risk factors and
      allostatic load. RESULTS: Rates of PAD were higher among African Americans (7.8%)
      than Whites (3.4%) or Mexican Americans (5.1%) (P<.001). African Americans with
      PAD were more likely to be taking antihypertensive medications, were less likely
      to report vigorous physical activity, and had higher allostatic load scores than
      Whites. Although 95% of individuals with PAD report a routine place for care,
      almost half had a measured blood pressure >140/90 mm Hg, 28% were smokers, and
      61% had a cholesterol value > or =200 mg/dL. CONCLUSIONS: Within this nationally
      representative sample, African Americans had the highest rates of PAD. Although
      conventional risk factor control, including control of hypertension and
      hyperlipidemia, were similar between racial groups, African Americans with PAD
      had higher allostatic load scores. Among all individuals with PAD, evidence
      showed suboptimal cardiovascular risk factor control.

PMID- 18072376
TI  - Acute exercise and postexercise blood pressure in African American women.
AB  - BACKGROUND: Limited data suggest that physical activity increases postexercise
      blood pressure in African-American women. The purpose of this study was to
      evaluate the postexercise blood pressure response to acute exercise in
      normotensive young adult African-American women. METHODS: Eight healthy women
      (age 22.5+/-.9 years) performed a cycle ergometer bout of 30 minutes at 60% of
      peak ventilatory oxygen uptake (VO2 peak). Control arterial blood pressure, heart
      rate, lower leg blood flow, cardiac output, spectral analysis of blood pressure,
      heart rate variability, and baroreceptor sensitivity were measured for 5 minutes
      before exercise and were compared to postexercise measurements performed at rest
      intervals of 15-20, 35-40 and 55-60 minutes after exercise. RESULTS: Exercise
      performed at 60% VO2 peak produced an arterial pressure of 172+/-10/ 70.1+/-4.0
      mm Hg. Postexercise recovery values were not significantly different than the
      baseline control values. CONCLUSION: These results do not support the hypothesis
      that acute physical activity exerts an adverse effect on postexercise blood
      pressure in African American women.

PMID- 18072378
TI  - A comparison of uric acid levels in Black African vs Caucasian women from South
      Africa: the POWIRS study.
AB  - OBJECTIVES: Elevated levels of uric acid are often associated with
      cardiometabolic risk factors. The aim of this study was to determine whether uric
      acid levels differ between African and Caucasian women and whether uric acid is
      associated with cardiometabolic risk factors within the two ethnic groups.
      METHODS: Women from African (N=102) and Caucasian (N=115) descent were recruited
      and their uric acid levels measured. Anthropometric measurements included height
      (stature), weight, and waist circumference. Correlations between uric acid and
      cardiometabolic variables within each ethnic group were also determined. RESULTS:
      African women had significantly lower levels of uric acid (P<.01) and
      significantly higher levels of blood pressure (P=.05) compared to the Caucasian
      women. There was a significant increase in blood pressure from the lower to
      higher uric acid tertiles in the African women. Uric acid strongly correlated
      with waist circumference in both ethnic groups. CONCLUSIONS: Despite their higher
      blood pressure, the African women had lower uric acid levels, yet they showed a
      significant increase in blood pressure from a low uric acid tertile to high uric
      acid tertile, which was not noticeable in the Caucasian women. A possible
      explanation is a lower waist circumference in African women compared to Caucasian
      women.

PMID- 18072379
TI  - Reduced cardiovascular fitness and ambulatory function in Black and White stroke
      survivors.
AB  - OBJECTIVES: To test the hypothesis that quantitative measures of cardiovascular
      fitness and ambulatory function differ in Black and White hemiparetic stroke
      survivors. DESIGN: Cross-sectional analysis. SETTING: Outpatient academic medical
      center. PARTICIPANTS: Total of 118 hemiparetic stroke survivors. MAIN OUTCOME
      MEASURES: Cardiovascular fitness was measured as VO2 peak and ambulatory function
      using the six-minute walk distance and 30-foot walking velocity in medically
      screened, community-dwelling stroke survivors. RESULTS: In 118 subjects (56%
      Black and 44% White), no differences were seen in 1) VO2 peak between Black or
      White men (15.0+/-4.3 vs. 15.1+/-3.9 mL/kg/minute) or women (11.5+/-2.7 vs.
      12.3+/-3.7 mL/kg/minute); 2) six-minute walk distance between Black or White men
      (223+/-112 m vs 226+/-132 m) or women (198+/-100 vs 157+/-93 m); or 3) 30-foot
      walking velocity between Black or White men (0.60+/-0.27 m/second vs 0.61+/-0.31
      m/ second) or women (0.50+/-0.21 m/second vs 0.41+/-0.23 m/second). CONCLUSION:
      No racial differences were seen in the degree of physical deconditioning in a
      selected population of community dwelling hemiparetic stroke survivors.

PMID- 18072380
TI  - Disability among older American Indians and Alaska Natives: disparities in
      prevalence, health-risk behaviors, obesity, and chronic conditions.
AB  - OBJECTIVES: To estimate the prevalence of disabilities among older American
      Indians and Alaska Natives (AIANs) and compare these estimates with those of
      other major racial/ ethnic groups. To estimate, within the population with
      disabilities, the health-risk behaviors, obesity, and chronic conditions of older
      AIANs and compare them with estimates for other racial/ethnic groups. DESIGN:
      State-based surveillance system that collects data on a monthly basis using an
      independent probability sample of households with telephones among the
      noninstitutionalized population aged > or =18 years. METHODS: We analyzed data on
      434,972 noninstitutionalized adults aged > or =50 years from the 2003-2005
      Behavioral Risk Factor Surveillance System. RESULTS: Among older AIAN adults, the
      unadjusted prevalence of disability (38.4%) was higher than among Whites (29.7%),
      Blacks (33.5%), Asians (15.6%), and Hispanics (26.9%). Among older adults with
      disabilities, AIANs were younger than their counterparts in other groups and were
      as likely to be male as female. After adjustment for age and self-rated health,
      both AIAN men and women with disabilities had the highest prevalence of current
      smoking, heart disease, and asthma. CONCLUSIONS: Efforts to prevent, delay, and
      reduce disabilities and associated secondary conditions in persons with
      disabilities must be culturally sensitive and targeted toward reducing
      racial/ethnic disparities in health-risk behaviors and chronic conditions.

PMID- 18072381
TI  - Continuity of care and hypertension control in a university-based practice.
AB  - OBJECTIVES: We describe the relationship between continuity of care and control
      of hypertension. DESIGN: Retrospective longitudinal cohort study of adults with
      hypertension. SETTING: University of North Carolina Family Medicine Center.
      PATIENTS: Hypertensive patients making at least four visits to the Center during
      a two-year period, 1999-2001. MAIN OUTCOME MEASURES: Longitudinal blood pressure
      level and dichotomous (<140 systolic and <90 systolic) blood pressure control.
      Independent variables include continuity of care, race and other demographic
      information, type of primary provider, and insurance type. RESULTS: Both systolic
      and diastolic BP fell over the two years (systolic 2.2 mm Hg/year and diastolic
      2.8 mm Hg/year). Lower systolic blood pressure was not associated with continuity
      of care, sex or provider type (faculty vs. resident). Lower diastolic blood
      pressure had a borderline association with continuity of care (2.2 mm Hg/year,
      95% CI -4.7, 0.4). Higher vs. lower continuity of care showed a trend toward
      better BP control, but the results were not significant (OR 0.84, 95% CI 0.65,
      1.09). Lower blood pressures were associated with Caucasian race (vs African
      American race). CONCLUSIONS: Continuity of care was not related to control of
      hypertension at our center. The factors related to hypertension control need
      further research.

PMID- 18072382
TI  - The association of language with prevalence of undiagnosed hypertension among
      older Mexican Americans.
AB  - OBJECTIVE: Language barriers have been shown to negatively impact health care for
      immigrants. We evaluated the association between language use and the diagnosis
      of hypertension among elderly Mexican Americans. STUDY POPULATION: We studied
      subjects from the Hispanic Established Populations for Epidemiologic Studies of
      the Elderly, a cohort of 3050 Mexican American subjects age > or =65. PREDICTORS:
      Measures of language included Spanish and/or English language read/spoken,
      language used in social situations, and language of mass media use. OUTCOME
      MEASURE: Undiagnosed hypertension on physical exam was defined as systolic blood
      pressure > or =140 mm Hg and/or diastolic blood pressure > or =90 mm Hg in
      persons who did not report previous hypertension diagnosis or were not current
      users of anti-hypertensive medications. RESULTS: The age- and sex-adjusted
      prevalence of diagnosed hypertension and undiagnosed hypertension were 50.5% and
      19.3%, respectively. Among 1347 older adults without previous diagnosis of
      hypertension that were included in the primary analysis, the mean age was 72
      years and 43% were immigrants. After adjusting for age, gender, and education,
      Spanish use more often than English use in mass media was significantly
      associated with undiagnosed hypertension (adjusted OR 2.2 [1.3-3.6]). Other
      measures of acculturation were not independently associated with undiagnosed
      hypertension. In analyses restricted to persons with hypertension, similar
      language factors distinguished those who had been diagnosed from those whose
      hypertension was undiagnosed. CONCLUSIONS: Mexican American elders who reported
      using Spanish more often than English use in mass media were more likely to have
      undiagnosed hypertension compared to those using English language in mass media.
      Further studies are needed to elucidate the role of mass media language in
      hypertension awareness and management among Hispanic elders.

PMID- 18072383
TI  - BMI tracking in Mexican American children in relation to maternal BMI.
AB  - OBJECTIVE: To assess body mass index (BMI [kg/m2]) tracking over a four-year
      period in 4- to 8-year-old Mexican American (MA) children and to explore
      associations between mother and child's BMI. DESIGN: A longitudinal study design
      was used to assess 138 subjects (69 MA children and 69 MA mothers). Children were
      classified as normal weight if age- and sex-specific BMI was < 85th percentile
      and overweight or at-risk for overweight if BMI was > or = 85th percentile.
      Mothers with a BMI < 25 kg/m2 were classified as normal weight and overweight if
      BMI was > or = 25 kg/m2. RESULTS: The percentages of children overweight or at
      risk for overweight were 34.8%, 36.2%, 40.6% and 39.1% for years 1-4,
      respectively. A positive correlation was found between the children's BMI status
      across the four years of the study (r=.90 to .95, P<.001). Furthermore, at-risk
      for overweight or overweight children in year 1 were highly likely to be
      overweight or at-risk for overweight in year 4 (adjusted OR: 67.7, 95% CI: 11.7
      386.4, P<.001). The correlation coefficients between mothers and daughters' BMIs
      during the four years were significant (P<.01), but not between mothers and sons'
      BMIs. CONCLUSION: Overweight or at-risk for overweight status tracks well during
      childhood and early adolescence among low-income MA children. Sex differences
      were found concerning associations between mother and their child's BMI.

PMID- 18072384
TI  - Relationship of diabetes with cardiovascular disease-related hospitalization
      rates, length of stay, and charges: analysis by race/ethnicity, age, and sex.
AB  - OBJECTIVE: Determine relationship of diabetes with risk of cardiovascular disease
      hospitalizations and the effect on hospital length of stay and charges. DESIGN: A
      cross-sectional analysis of Georgia hospital discharge data for 1998 through
      2001. PATIENTS: Patients hospitalized principally with one of six cardiovascular
      disease (CVD) conditions (myocardial infarction, ischemic heart disease, cardiac
      dysrhythmia, heart failure, cerebrovascular events, peripheral vascular disease)
      were identified in the hospital discharge data. MAIN OUTCOME MEASURES: Aggregated
      CVD-related hospitalization rates, length of stay, and charges were compared by
      presence of diabetes. Analyses were adjusted for age, sex, and race/ethnicity.
      RESULTS: A total of 3,900,337 discharges were recorded between 1998 to 2001. Of
      these, 468,957 discharges (12%) had one of the six selected CVD diagnoses
      (average age 67 years, average length of stay 4.7 days, average total charge
      $15,702, 48% women, 76% non-Hispanic Whites, 22% non-Hispanic Blacks, and 1%
      Hispanics). Diabetes was a concurrent diagnosis in 30% of these CVD-related
      discharges. CVD hospitalization rates were significantly higher and length of
      stay and total charges were significantly greater among non-Hispanic Whites and
      Blacks-but not in Hispanics-with diabetes compared to persons without diabetes.
      Diabetes had a similar effect on CVD hospitalizations among men and women, but
      the effect of diabetes was lessened with increasing age. CONCLUSION: These data
      suggests that aggressive outpatient modification of metabolic abnormalities in
      diabetes patients should be attempted to decrease risk of CVD-related
      hospitalization and lower the economic impact of these combined conditions.

PMID- 18072385
TI  - Prognostic indices of diabetes mortality.
AB  - INTRODUCTION: Diabetes mellitus is an important cause of morbidity and mortality
      worldwide and the burden associated with it is felt more in developing countries.
      Communicable diseases, as opposed to non-communicable diseases, remain a top
      priority in developing countries like Nigeria. This report sets out to highlight
      the current status of diabetes-related hospitalizations in Nigeria and also to
      make comparisons with past reports. This goal will be achieved primarily by
      determining the prognostic factors associated with diabetes mortality and also
      noting the duration of hospital stay for the major causes of diabetes deaths.
      METHOD: From January through December 2006, subjects with diabetes mellitus (DM)
      in a tertiary hospital in Nigeria were prospectively studied after admission to
      assess their shortterm outcome which was defined as death. The total mortality,
      causes of death, associated complications and duration of hospital stay were
      noted. The predictive factors for DM morbidity were evaluated using chi test,
      logistic regression. Students t test was computed for quantitative data. RESULTS:
      A total of 1,327 subjects were admitted to the Medical wards for the duration of
      the study and the crude death rate was 11%. DM related admissions made up 206
      (15%) of all the medical admissions and the case fatality rate was 33 (16%). The
      most common reasons for DM admission were hyperglycaemic emergencies (HE), 88
      (40%) and hypertension, 44 (21%). The most common causes of deaths were HE, 15
      (46%) and DM foot ulcers (DFU), 10 (30%) while DFU and cerebrovascular accident
      (CVA) had the highest case fatality rates of 28% and 25% respectively. DFU had
      the most prolonged duration of admission ranging from 15-122 days. DFU, CVD and
      having type 2 DM were highly predictive of fatal outcomes. The odds ratio and 95%
      CI for these factors were 4.5 (1.5-12.7), 3.0 (0.9-9.92 and 3.1 (0.7-14)
      respectively. CONCLUSION: DFU and HE are potentially remediable causes of
      mortality in DM. DFU as seen by the prolonged hospital stay imposes a huge burden
      on health resources. Better and early intervention of DFU is necessary to reduce
      the resultant disease burden.

PMID- 18072386
TI  - Prevalence and predictors of microalbuminuria in patients with diabetes mellitus:
      a cross-sectional observational study in Kumasi, Ghana.
AB  - OBJECTIVE: To evaluate the prevalence and predictors of microalbuminuria in
      diabetics in Kumasi, Ghana. DESIGN: Prospective, cross-sectional study of
      diabetic patients. SUBJECTS: Patients with diabetes, 20 to 78 years of age. MAIN
      OUTCOME MEASURES: Microalbuminuria METHODS: All patients (109) attending an
      outpatient diabetic clinic at the Komfo Anokye Teaching Hospital Diabetes Centre
      in Kumasi, Ghana from January to July 2005 were enrolled in the study. RESULTS:
      The mean overall age of the cohort was 54.1 +/- 10.9 years, and 28% were male.
      The proportion of subjects who had microalbuminuria was 43.1% (n=47). The median
      duration of diabetes before development of microalbuminuria was 10 years.
      Duration of diabetes, blood urea nitrogen, serum concentration of creatinine, and
      triglyceride were significantly higher in patients with microalbuminuria (P<.05).
      Urinary potassium concentration and fractional excretion of potassium were also
      significantly higher in the patients with microalbuminuria. CONCLUSIONS: The
      prevalence of microalbuminuria in patients with diabetes in this study was 43%.
      Significant predictors of microalbuminuria included duration of diabetes and
      serum concentration of creatinine. To reduce renal failure among these patients,
      strategies to mitigate its occurrence are needed. This includes strict glycemic
      control, control of hypertension, and the early blockade of the renin-angiotensin
      system.

PMID- 18072387
TI  - Internalized racism is associated with elevated fasting glucose in a sample of
      adult women but not men in Zimbabwe.
AB  - OBJECTIVES: Internalized racism (INR) is associated with metabolic abnormalities
      among African Caribbean women. The current study was conducted to determine if
      similar associations exist among Black women living in Africa. METHODS: In 2003,
      a stratified random sample of Black adults ages > or =18 years was drawn from
      four high-density suburbs of the city of Bulawayo, Zimbabwe. A total of 318
      persons (90% of those recruited) participated. Face-to-face interviews were used
      to gather information on demographic variables, health history, internalized
      racism, anthropometric measurements and blood pressure. Internalized racism, the
      extent to which individuals agree with racist stereotypes about their race, was
      measured with a standardized questionnaire. A fasting blood sugar level was also
      measured for each participant. Persons with diagnosed diabetes or incomplete data
      (n=44) were excluded from analyses. RESULTS: Women (n=188) and men (n=86) did not
      differ significantly by age, INR score, waist circumference or fasting glucose
      level. The mean body mass index of women (23.6 kg/m2) was higher (P<.05) than
      that of men (22.3 kg/m2). INR was significantly correlated with waist
      circumference, diastolic blood pressure and fasting glucose among women but not
      among men. In multiple logistic regression analyses using the data for women, a
      high INR remained independently associated with abnormal fasting glucose (odds
      ratio=2.74, P=.0085) after adjusting for potential confounders including
      adiposity. CONCLUSIONS: These findings show the consistency of the association of
      high INR with metabolic abnormalities among Black women in the Diaspora.

PMID- 18072388
TI  - Descriptive and clinical epidemiology of preeclampsia and eclampsia in Florida.
AB  - OBJECTIVE: To calculate preeclampsia/eclampsia rates for Florida and identify
      risk factors for prolonged length of stay (PLOS) among women hospitalized
      throughout Florida for preeclampsia/eclampsia and discharged in 2001. DESIGN:
      Analyses were performed using a statewide hospital discharge dataset from
      Florida. Hospital discharge rates per Florida female population and risk per 100
      deliveries were calculated for women hospitalized for preeclampsia. Binomial
      regression was used to calculate relative risks (RR) of PLOS among 5495 women.
      Generalized estimating equations were used to account for nesting by facility.
      RESULTS: Non-Whites had higher preeclampsia discharge rates per 10,000 population
      than Whites in every age group. The overall risk of preeclampsia was 3.9 per 100
      deliveries, with the highest risks in the youngest and oldest age groups. The
      strongest risk factor for PLOS was having a diagnosis of preeclampsia/eclampsia
      superimposed on pre-existing hypertension. These patients had 2.64 times the risk
      of PLOS than patients who had mild or unspecified preeclampsia (P value <.0001).
      Diabetics were also at a higher risk of PLOS (adjusted RR=1.26, P=.003). Women
      who were admitted from the emergency department were 26% less likely than women
      admitted from other sources to have PLOS (adjusted RR=.74, P=.01). For every 10
      year increase in maternal age, there was a 23% increase in the risk of PLOS
      (adjusted RR=1.23, P<.0001). CONCLUSIONS: Advancing maternal age, Black race,
      diabetes, severe preeclampsia, and preeclampsia (or eclampsia) superimposed on
      existing hypertension increased the risk of PLOS, while being admitted from the
      emergency department was associated with a decreased risk of PLOS.

PMID- 18072389
TI  - Leave no asthmatic child behind: the cultural competency of asthma educational
      materials.
AB  - OBJECTIVE: Cultural competency leads to higher quality care for asthmatic
      children, yet it is not known whether asthma educational materials targeting
      minority children and families are culturally competent. The study objective was
      to evaluate the cultural competency of printed asthma educational materials
      targeting minorities in Wisconsin. PATIENTS AND METHODS: The Wisconsin Asthma
      Coalition Disparities Workgroup held a series of meetings to develop, test, and
      apply a tool for evaluating the cultural competency of asthma educational
      materials targeting minorities in Wisconsin. The tool consists of seven domains:
      language, normative cultural values, folk illnesses, parent/patient beliefs,
      provider practices, visuals, and an overall assessment. Asthma educational
      materials were obtained from healthcare organizations and clinics. All seven
      domains were scored using a 5-point Likert scale. RESULTS: Only 17 asthma
      educational materials targeting minorities exist in Wisconsin: 16 for Latinos,
      one for Native Americans, none for African Americans, and none for Asians/Pacific
      Islanders. Overall assessment scores for each material ranged from 1-2 (poor
      fair), with a mean+/-SD=1.4+/-0.5. The highest mean domain scores were for
      language (3.5+/-1.2) and illustrations (3.4+/-1.4); the lowest score was for folk
      illnesses (1.1+/-0.2), with weaknesses identified for parent/patient beliefs
      (1.8+/-0.7); provider practices (1.8+/-0.7); and normative cultural values (2.5+/
      0.7). CONCLUSIONS: The few asthma educational materials targeting minorities that
      exist in Wisconsin are not culturally competent. More culturally competent asthma
      educational materials for minorities are needed.

PMID- 18072390
TI  - Strategies for health promotion: facing the challenge in South Africa.
AB  - Many health promotion intervention studies have been conducted with the goal of
      encouraging people to change their lifestyles. These include interventions in the
      community, at worksites, in a medical setting, and on patients at high risk of
      disease. These interventions have had, in general, a limited impact (eg, risk of
      heart disease is lowered by 5%-15%). These interventions were carried out in
      developed countries, and little is known as to their effectiveness in developing
      countries such as South Africa. Numerous barriers impede the success of health
      promotion interventions, including the cost of healthy food, advertising for
      unhealthy food, and food labels that are confusing. Policy measures are proposed,
      including government interventions using taxes and subsidies so as to manipulate
      prices and bring about desirable changes in eating patterns and other aspects of
      lifestyle. A new type of healthcare professional is suggested with a
      specialization in health promotion.

PMID- 18072391
TI  - For the patient. Views on US health care by immigrant women in Michigan.

PMID- 18072392
TI  - For the patient. Spiritual program proven to reduce high blood pressure.

PMID- 18072393
TI  - For the patient. How health disabilities affect American Indians and Alaska
      Natives.

PMID- 18072394
TI  - For the patient. Exercise can improve your health.

PMID- 18072396
TI  - The profession in the 21st century.

PMID- 18072395
TI  - For the patient. Diabetes-related deaths in Lagos, Nigeria.

PMID- 18072397
TI  - Chicken collagen type II reduces articular cartilage destruction in a model of
      osteoarthritis in rats.
AB  - AIM: To evaluate the therapeutic effects of domestic chicken collagen type II
      (CCII) on rat osteoarthritis (OA) and analyze concomitant changes in the level of
      Matrix metalloproteinase (MMP)-13, MMP-9, Cathepsin K and their mRNA as well as
      the tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA in articular
      cartilage of osteoarthritic rats. METHODS: Osteoarthritis models were surgically
      induced. Morphology of articular cartilage was done by haematoxylin and eosin
      staining and Mankin score was calculated, immunohistochemistry of MMP-13, MMP-9
      and Cathepsin K was done by ABC method while the mRNA level for MMP-13, MMP-9,
      cathepsin K as well as TIMP-1 was evaluated by RT-PCR method. RESULTS: Oral
      administration of CCII reduced the morphological changes of osteoarthritic
      cartilage (shown by Mankin score), decreased levels of MMP-13, MMP-9, cathepsin K
      as well as their mRNA in articular cartilage from osteoarthritic rats while it
      exhibited no effect on TIMP-1 mRNA. CONCLUSION: Oral CCII reduced articular
      cartilage degradation of osteoarthritic rats and may probably be a potent drug
      candidate for OA treatment.

PMID- 18072398
TI  - Ethics, liabilities and licensing to practice.
AB  - Medical Councils or Boards are the de facto gatekeepers of the work of medical
      doctors and their interaction with the public. This article examines some of the
      ethical and medico-legal issues that may arise when biomedical doctors are not
      licensed in a particular year to practice medicine. It scrutinizes pertinent
      sections of the Medical Act of Jamaica and considers the ethical implications of
      the particular predicament for patients and pharmacists who are requested to fill
      prescriptions written by doctors who are not in receipt of a practising
      certificate at the time.

PMID- 18072399
TI  - Gender, acculturative stress and Caribbean immigrants' health in the United
      States of America: an exploratory study.
AB  - Given that the health of many immigrants declines after increasing years in their
      host countries and that there may be gender differences in these experiences,
      this exploratory study's main objective was twofold: a) assess the relationship
      between acculturative stress and negative health (ie both mental and physical)
      and b) determine if there were any gender differences in these stress-health
      relationships. Gender-stratified analyses were conducted on a sample of 418
      (males = 158, females = 260) English-speaking immigrants (the majority of whom
      were Jamaicans--males = 81%, females = 86%) that lived in the District of
      Columbia, Virginia, and Maryland (DC Metropolitan Area, United States of America
      (USA). Mail-order surveys were used to collect the data over a six-month period
      in 2002. Data for the main independent variable, acculturative stress, were
      collected using five indices (ie personal problems, group affiliations,
      adjustment to life in the USA, lonely feelings and feeling socially satisfied).
      Data for the major dependent variable, health, were collected using four indices
      (ie symptoms of depression, physical health conditions, the rating of one's
      health and the feeling of control one had over one's health). After controlling
      for selected covariates, both males (r = 0.42, p < 0.001) and females (r = 0.19,
      p < 0.05) reported a positive relationship between personal problems and
      depression. In other cases, female immigrants, with increasing personal problems,
      reported more physical health problems (r = 0.20, p < 0.05). Male immigrants who
      had more group affiliations (r = 0.22, p < 0.05), and who reported more
      loneliness (r = .26, p < 0.05) had less symptoms of depression. These exploratory
      results suggest the potential importance of selected variables (eg personal
      problems and depression) in efforts at improving the health of Caribbean
      immigrants.

PMID- 18072400
TI  - The aetiology of head injury in admitted patients in Jamaica.
AB  - This cross-sectional, descriptive study identified 857 head-injured patients who
      were admitted to the University Hospital of the West Indies (UHWI) over a four
      year period. Their median age (IQR) was 28 (16, 45) years and 629 (73.5%) were
      males. Median length of hospital stay (IQR) was 2 (1, 6) days. Median ICU stay in
      the intensive care unit (IQR) was 6 (2, 12) days for the 59 (6.9%) patients
      admitted there. Most patients (73.3%) were admitted with unintentional injuries
      resulting from road traffic accidents (48.9%), of which passengers were the most
      commonly affected, and from falls which occurred in 24.4%. Intentional injuries
      accounted for 26.7% of those admitted, consisting mainly of assaults with blunt
      objects in 18.0% (154/857). Penetrating injuries were less common, accounting for
      67 (7.8%) injuries. Among these, there were 23 gunshot wounds of the head (2.7%).
      Head injury in admitted patients is mainly due to road traffic accidents, falls
      and interpersonal violence. Prevention and interventional strategies including
      education, law enforcement, physical and social engineering must focus on these
      aetiologies. Current measures are clearly insufficient and more effective
      strategies are urgently warranted.

PMID- 18072401
TI  - Unnecessary admissions of head-injured patients at the University Hospital of the
      West Indies.
AB  - The prospectively collected data in the Jamaica National Trauma Registry operated
      by the Section of Surgery identified 88 patients who were admitted with head
      injury to the University Hospital of the West Indies over a one-year period.
      There were 67 males (76.1%), the mean (SD) age of the entire group being 35.02
      (+/- 18.45) years. Intentional injuries occurred in 47.2%. The Injury Severity
      Score was greater than 15 in 19.3%, severe head injuries occurred in 19% and
      overall mortality was 16%. Care in the Intensive Care Unit (ICU) was extended to
      only half of those with the severe injuries. The Scottish Intercollegiate
      Guidelines Network (SIGN) method was used to assess the appropriateness of
      admission to hospital. Sixteen (18%) of the 88 patients were inappropriately
      admitted according to SIGN guidelines. Increased efficiency may result from
      standardization of admission criteria for head-injured patients and consistent
      implementation of the SIGN guidelines for admission without increased risk to
      patients. This may be expected to minimize unnecessary admissions and result in
      considerable cost savings.

PMID- 18072402
TI  - Surgical and intensive care needs of head-injured patients transferred to the
      University Hospital of the West Indies.
AB  - A cross-sectional, descriptive study utilizing data collected in the 'Trauma
      Registry' of the Department of Surgery, Radiology, Anaesthesia and Intensive Care
      at the University Hospital of the West Indies (UHWI) was undertaken to document
      injury severity, surgical requirements and intensive care needs of head-injured
      patients transferred to the UHWI over a three-year period Of 144 patients
      studied, the majority (71%) were young males. Overall, injury tended to be mild
      Twenty-three patients (16.0%) had severe head injury and 27 patients (18.8%) were
      admitted to the intensive care unit. Concussion with (33%) or without (36%) skull
      fracture was the commonest neurological admission diagnosis. Associated non
      neurological injuries in 33% were primarily fractures. Fifty-six patients (39%)
      required surgical intervention. Craniotomies and open reduction and internal
      fixation of fractures were the commonest procedures. The majority of patients
      (79.2%) were discharged home; 56 (39%) made a good Glasgow outcome score
      recovery. Seventeen patients (11.8%) died in hospital. As most of the transferred
      patients with head injuries in this study had only mild injury, most commonly
      concussions, and their prognosis was good, we recommend that appropriate
      educational and training programmes and transfer policies be implemented to
      minimize inappropriate transfers.

PMID- 18072403
TI  - Trinidad motorists' understanding of safety belt issues.

PMID- 18072404
TI  - Association between exposure/non-exposure to the mandatory seat belt law with
      regards to compliance in vehicle accident victims--a hospital review.
AB  - OBJECTIVE: Injuries sustained in motor vehicle accidents (MVAs) are a major
      challenge to the Jamaican healthcare system. In November 1999, Jamaica enacted
      legislation to make seat belt usage in motor vehicles compulsory. The effect of
      this policy change on seat belt usage is unclear. This study therefore sought to
      determine the prevalence of seat belt usage and to determine the association
      between exposure/non-exposure to the mandatory seat belt law and seat belt use in
      subjects who presented to the Accident and Emergency Department (A&E) of the
      University Hospital of the West Indies (UHWI) as a result of motor vehicle
      accidents. METHODS: Subjects were recruited from June to November 2003, post-seat
      belt law (POBL) period, and May to October 1999, pre-seat belt law (PRBL) period.
      Data collected included demographic variables, seat belt use and position of the
      occupants in the vehicle. RESULTS: Of the 277 patients who were eligible for
      inclusion, data were complete in 258 subjects, 87 in the PRBL period and 171 in
      the POBL period. The prevalence of seat belt use was 47% (PRBL) and 63% (POBL)
      respectively. There was no significant gender difference at each period. The odds
      of wearing seat belt in the rear of a motor vehicle were significantly lower than
      that of a driver (Table 3, OR 0.19, 95% CI 0.07, 0.48). Adjusting for age, gender
      and position in vehicle exposure, there was about 100% increase in the odds of
      seat belt use during the post seat belt law era (OR = 2.09, 95% CI 1.21, 3.61).
      CONCLUSION: It is concluded from this hospital-based study that the mandatory
      seat belt law legislature was associated with increased seat belt use in motor
      vehicle accident victims. However, current data from the Road Traffic Agency
      indicate that there is still an alarming number of fatalities. This clearly
      suggests that additional public health measures are needed to address the
      epidemic of motor vehicle trauma in Jamaica.

PMID- 18072405
TI  - Risk-adjusted outcome evaluation in a multidisciplinary intensive care unit.
AB  - OBJECTIVE: To evaluate the outcome of a multidisciplinary Intensive Care Unit
      (ICU) by applying the Acute Physiology and Chronic Health Evaluation (APACHE II)
      and Paediatric Index of Mortality (PIM)--version-2 scoring systems. SUBJECTS AND
      METHODS: Two-hundred and seventeen patients admitted consecutively to the ICU
      during a period of one year were included for prospective data collection. Data
      recorded were demographics, diagnoses at admission, APACHE II score for adults
      and PIM -2 score for children, the duration of ICU stay and hospital outcome.
      Predicted mortality and standardized mortality ratios were calculated.
      Calibration and discriminant function of the systems were done by Hosmer-Lemeshow
      analysis and Receiver Operating Characteristic (ROC) curves. RESULTS: In adults,
      the mean APACHE II score was 14.3 +/- 8.3; in survivors, it was 8.7 +/- 5.9 (SD)
      when compared to 21.2 +/- 5.9 (SD) in non-survivors (p < 0.0001). The predicted
      mortality in adults by APACHE II was 16.5%, the observed mortality being 19.8%.
      The predicted mortality by the PIM-2 in children was 34.8% with the observed
      mortality rate being 30%. The overall mean duration of stay was 5.2 +/- 7.5 days.
      The goodness-of-fit for APACHE II and PIM-2 systems were fair (HL chi-square, p =
      0.71, 0.69, respectively). The area under the ROC curve was 0.88 for APACHE II
      and 0.62 for PIM-2. CONCLUSION: Evaluation of risk-adjusted outcome in
      multidisciplinary ICUs is challenging because of the need to apply more than one
      prognostic scoring system.

PMID- 18072406
TI  - The Illizarov method in infected non-union of long bones.
AB  - OBJECTIVE: To review the results of the management of infected non-union of long
      bones using the Illizarov fixator. METHODS: Eight patients with non-union of long
      bones associated with current or prior infection were treated between 1998 and
      2006. Seven patients were treated between 2004 and 2006. There were seven males
      and one female with an average age of 32 years (range 17-53 years). Four non
      unions were located in the tibia, two were present in the humerus, one was
      present in the femur and one was intraarticular. Five non-unions were treated
      with acute compression, two were treated with bone transport and the frame was
      used in a static mode in one. RESULTS: There was one excellent, three good, one
      fair and three poor results. CONCLUSION: The Illizarov technique is an important
      treatment method for surgeons performing posttraumatic reconstructive surgery.
      Non-union, infection, shortening and deformity are all addressed simultaneously.

PMID- 18072407
TI  - Role of obesity in low back pain related disability.

PMID- 18072408
TI  - Do the unmet needs affect the quality of life in breast cancer patients?
AB  - OBJECTIVE: Breast cancer is an important disease and one where healthcare
      services have the potential to improve the quality of life. The aim of this study
      was to assess the relationship between unmet needs and the quality of life (QoL)
      of breast cancer patients. SUBJECTS AND METHODS: This study comprised one hundred
      breast cancer patients who attended the Oncology Outpatient Clinic in Cukurova
      University between April and June 2001. Three questionnaires were used:
      questionnaires for demographic details, unmet needs and Functional Assessment of
      Cancer Therapy-General Questionnaire QoL. RESULTS: There was significant
      correlation between QoL score and unmet needs score (r = 0.263, p = 0.008) and
      between QoL score and Napier logarithm (monthly income) (r = 0.257, p = 0.011).
      There was a significant difference in QoL score by occupation (p = 0.007).
      CONCLUSION: It is important to assess patients psychologically so as to make
      interventions about their psychosocial needs which affect QoL. This will require
      the re-evaluation of doctor-patient communication and interventions for
      improvement of this relationship.

PMID- 18072409
TI  - Prospective evaluation and characteristics of patients with suspected primary
      hyperaldosteronism.
AB  - Primary hyperaldosteronism (PH), resulting in hypokalaemic hypertension, may be
      due to an aldosterone-producing adenoma (APA) or bilateral zona glomerulosa
      hyperplasia. Six patients with suspected PH were identified at the University
      Hospital of the West Indies and standardized screening was carried out. Plasma
      renin activity (PRA) and serum aldosterone concentrations (SAC) were measured,
      followed by confirmatory intravenous saline suppression test. The patients were
      all women, of median age 48 years (interquartile range, IQR: 41-51.7 years). They
      tended to be overweight with suboptimal blood pressure control. Median serum
      potassium was 3.1 mmol/L (IQR 2.7 - 3.3 mmol/l) and kaliuresis was elevated or
      inappropriately normal. All individuals had suppressed PRA (< 0.6 ng/ml/hr) and
      elevated SAC (> 30 ng/dl), with SAC/PRA ratios > 50. Five patients had confirmed
      PH (ie post-saline SAC > 10 ng/dl); PH could not be definitely excluded in the
      sixth patient (ie post-saline SAC 5 - 10 ng/dl). Imaging studies revealed normal
      adrenal glands in one patient, unilateral adrenal enlargement in three patients,
      and unilateral adrenal masses in two patients. Only one of these latter two
      patients was shown to have an adrenal adenoma on histological examination. In
      this series, there appears to be fewer cases of the APA subtype of PH than
      expected. It remains to be seen whether the distribution of PH subtypes in
      Jamaica is actually different from elsewhere. This, and the cost-effectiveness of
      different approaches to screening, identification and management of patients
      suspected of having PH in Jamaica are areas for further study.

PMID- 18072410
TI  - Trends in the incidence of type I diabetes mellitus worldwide.
AB  - The incidence of Type I diabetes mellitus in children has increased worldwide
      over the past 50 years. This increase has occurred in rich and poor countries in
      Europe, Asia, the Americas and Oceania. Rapid increases in incidence in
      genetically stable populations eg Finland and Sardinia imply that environmental
      factors are of paramount importance as driving forces in this changing trend. The
      significance of these trends and putative aetiological factors are reviewed.

PMID- 18072412
TI  - Beyond cholecystectomy: advanced laparoscopic surgery in practice and training in
      the Caribbean.

PMID- 18072411
TI  - The mean levels of adherence and factors contributing to non-adherence in
      patients on highly active antiretroviral therapy.
AB  - OBJECTIVE: To determine the mean level of adherence and factors contributing to
      non-adherence in patients on Highly Active Antiretroviral Therapy (HAART).
      METHODS: An observational study was done on 101 HIV/AIDS patients attending the
      Centre for HIV/ AIDS Research, Education and Services (CHARES) - University
      Hospital of the West Indies, between May 2006 and August 2006. A questionnaire
      was administered asking questions re: prescribed and actual dosing frequency and
      number of antiretroviral tablets for the previous week, reasons for nonadherence,
      duration of Highly Active Antiretroviral Therapy, age, employment status and
      level of education. Mean levels of adherence were calculated using self and
      social worker/nurse reported dosing frequency and number of tablets. Good
      adherence was defined as 95% or greater. Multiple regression analysis was used to
      determine factors impacting on adherence. RESULTS: Ninety-six patients were
      included for final analysis. Mean levels of adherence were as follows: 87.66%-
      self-report for tablets; 88.70%--self-report for dosing frequency; 87.02%--social
      worker/ nurse report for tablets; 88.10%--social worker/nurse report for dosing
      frequency. There were significant positive correlations between self and social
      worker/nurse reports using dosing frequency (Spearman Rho correlation coefficient
      0.943, p = 0.01) or number of tablets (Spearman Rho correlation coefficient
      0.955, p = 0.01). Adherence to self-reported number of tablets and dosing
      frequency were 58.4% and 56.4% respectively. Duration of HAART was found to have
      a significant negative correlation with the level of self-reported adherence to
      tablets (p = 0.002). CONCLUSION: Adherence to HAART is sub-optimum in patients at
      the CHARES. This must be urgently addressed to prevent the development of
      resistant HIV strains and treatment failure.

PMID- 18072413
TI  - Six years experience of angioedema at the University Hospital of the West Indies.
AB  - Angioedema (AE) is a problem that all doctors inclusive of emergency room
      physicians and the otolaryngologists are often asked to treat. We present a six
      year experience with this disorder. In this series, angiotensin-converting enzyme
      inhibitors (ACEIs) were related to 60% of admissions for angioedema. Lip and
      tongue swelling was the most common manifestation. The discontinuation of ACEI
      therapy and supportive management are the recommended approaches to treatment and
      prevention of unfavourable outcomes. The authors strongly recommend medic alert
      bracelets for all patients with this disorder. The use and side effects of ACEI
      therapy in our population which is predominantly of African descent warrants
      further investigations.

PMID- 18072414
TI  - Moyamoya disease associated with positive findings for rheumatoid factor and
      myeloperoxidase-anti-neutrophil cytoplasmic antibody.
AB  - A 39-year old female suddenly fell into a state of unconsciousness. She had no
      significantpast medical history. A computed tomography scan of the head
      demonstrated a massive left putaminal haemorrhage with a ventricular perforation,
      low density areas in the right frontal lobe, corona radiata and occipital lobe. A
      single emergency burr hole drainage of the haematoma was performed. Bilateral
      common carotid arteriograms showed stenosis of the right internal carotid artery
      and a complete obstruction of left internal carotid artery which were both
      accompanied by moyamoya vessels. The biochemical studies indicated serological
      positive findings for RF and MPO-ANCA. She was transferred to another hospital
      for nursing care in a vegetative state on the 163nd hospital day. This case
      indicates that immunological factors, inflammation or vasculitis might have
      possibly been associated with the development of either an obstruction or
      stenosis of the intracranial internal carotid arteries.

PMID- 18072415
TI  - Obstruction of the duodenum by a preduodenal portal vein in situs inversus.
AB  - Mirror image transposition of abdominal and thoracic viscera is termed situs
      inversus. Duodenal obstruction in situs inversus is rare. A preduodenal portal
      vein, though not uncommon in situs inversus, rarely causes duodenal obstruction.
      Where obstruction by a preduodenal portal vein is diagnosed, a duodeno
      duodenostomy is the recommended treatment. A duodenal diaphragm and other more
      common causes of duodenal obstruction should also be excluded in these patients.

PMID- 18072416
TI  - Penetrating neck trauma and the aberrant subclavian artery.
AB  - Vascular injuries from penetrating trauma to the base of the neck are accompanied
      by significant morbidity and potential mortality. These injuries require several
      diagnostic adjuncts in order to facilitate early diagnosis and appropriate
      treatment. Herein reported is the case of a patient who sustained penetrating
      injury to the thoracic inlet but had a fortuitous anomaly that prevented vascular
      injury and its attendant complications.

PMID- 18072417
TI  - Treatment of congenital pseudarthrosis of the tibia with the Ilizarov technique.
      Case report and review of the literature.
AB  - Congenital pseudarthrosis of the tibia continues to pose one of the most
      difficult problems in paediatric orthopaedic surgery. The surgical procedures
      most used for treating congenital pseudarthrosis of the tibia are intramedullary
      nailing associated with bone grafting, vascularized fibular graft and the
      Ilizarov external circular fixator. Even when union is achieved, the residual
      deformities in the affected limb often result in significant disability. These
      deformities include leg-length discrepancy, angular tibial deformities, ankle
      mortise valgus and fibular non-union. The Ilizarov method allows simultaneous
      excision of the pseudarthrosis site, correction of the deformity and lengthening.
      However, refractures, ankle joint stiffness, fibular non-union with progressive
      ankle valgus are frequent sequelae with the Ilizarov technique. The surgeon
      should know when to abandon reconstructive procedures and create a more
      functional patient with an amputation. The authors discuss the indications and
      results of the Ilizarov external fixator in two patients with this complex
      problem. In addition, a critical review of the current literature is undertaken.

PMID- 18072418
TI  - Acute renal failure post coronary artery bypass grafting at the University
      Hospital of the West Indies.
AB  - OBJECTIVES: The purpose of the study was to determine the period prevalence of
      acute renal failure (ARF) after coronary bypass surgery (CABG) at the University
      Hospital of the West Indies and to identify risk factors. METHOD: A retrospective
      analysis of patients who underwent CABG during the period 1994-2004 was done.
      Data collected included; age, gender, weight, the presence of hypertension (HTN),
      diabetes mellitus (DM), hypercholesterolaemia, previous myocardial infarction
      (MI), blood pressure on admission, urea and creatinine one year prior to surgery,
      on admission for surgery and post-surgery, duration of intra-operative
      hypotension, duration of cardiopulmonary bypass, perfusion pressure and the
      perioperative medications. RESULTS: The case notes of 62 patients (68.9%) were
      obtained for analysis. There were 47 (75.8%) males and 15 females (24.2%)--a 3:1
      ratio. The prevalence of HTN and DM in the study sample was 78% and 72%
      respectively, hypercholesterolaemia was 31% and a previous MI was 29%. There were
      no differences based on gender. Post CABG complications were: persistent
      postoperative hypotension (6.8%), congestive cardiac failure (CCF) (6.8%),
      arrhythmia (6.8%), sepsis (6.8%), lower respiratory tract infection (LRTI) and
      pleural effusion (5.1%), heart block (3.4%), pulmonary embolism (1.7%),
      cellulitis and haematoma formation were 1.7%. Three patients had increases in
      postoperative creatinine values > 89 micromol/L over the postoperative value
      resulting in a prevalence of ARF of 5%. One of the three patients died and none
      received dialysis. There were no statistical difference in pre-operative clinical
      and biochemical characteristics based on the presence or absence of ARE. The
      presence of diabetes and increased length of stay were significant predictors of
      increasing postoperative creatinine values adjusting for pre-operative creatinine
      values. In addition, the presence of diabetes mellitus and male gender were
      significant predictors of increasing postoperative urea values. CONCLUSION: DM is
      a significant risk factor for the development of ARF post CABG.

PMID- 18072419
TI  - Cardiac disease in dialysis patients in a Jamaican hospital: echocardiographic
      findings that predict mortality.
AB  - The aim of the study was to assess, by echocardiography, the cardiac
      abnormalities in a group of patients with chronic renal failure and to determine
      the cardiovascular predictors of mortality. The study comprised forty-five
      patients from the Renal Unit, University Hospital of the West Indies, Kingston,
      Jamaica, and was undertaken between October 1, 1998 and July 31, 2000. All
      echocardiography was done by a single operator. The parameters assessed were
      systolic dysfunction, diastolic dysfunction, ejection fraction, regional wall
      motion abnormalities and valvular disease. Left ventricular cavity size, septal
      and posterior wall thickness were measured and left ventricular mass calculated.
      Demographic data were obtained directly from each patient by interview. The
      patients were mainly of African/mixed-African origin. Their mean age was 43.2 +/-
      16.0 years. The average body mass index was 23.7 +/- 6.9. Twenty-eight (60.9%)
      patients were male and seventeen (39.1%) female. Hypertension, chronic
      glomerulonephritis and diabetes mellitus were the leading causes of chronic renal
      failure. Blood pressure was controlled at a mean value of 145/90 mm Hg pre
      dialysis and 140/90 mm Hg postdialysis. The mean duration of renal failure was
      2.8 years. Echocardiographic M-mode and two dimensional apical, four chamber view
      measurements indicated that mean left ventricular internal diameter (LVID)
      diastole was 55.7 +/- 7.9 mm (normal 38-56 mm) and LVID systole was 38.9 +/- 9.8
      mm (normal 24-45 mm); the mean thickness of the chamber walls was 10.3 +/- 2.8 mm
      and 10.6 +/- 2.4 mm for the interventricular septum (normal 6-11 mm) and left
      ventricular posterior wall (normal 6-11 mm) respectively. Diastolic dysfunction
      was seen in 15 (34%) patients and systolic dysfunction in 12 (23%) patients who
      had ejection fractions less than 50%. The mean left ventricular ejection fraction
      was 56.3% +/- 16% (normal 65-85%), mean stroke volume was 82.9 +/- 27.2 mls
      (normal 51-96 ml). After 21 months enrolment in the study, Kaplan Meier analysis
      revealed a two-year mortality of 28.3%. Cox regression analysis indicated that a
      history of smoking current or past, low haemoglobin level, high aorta flow
      velocities, severity of mitral regurgitation and a negative association with
      serum creatinine were independent predictors of mortality. The correction of
      anaemia and control of other factors that impact negatively on cardiac function
      in dialysis patients is vital to enhance survival.

PMID- 18072420
TI  - Analysis of pre-suicide signs: implications for suicide prevention.

PMID- 18072421
TI  - Escherichia coli and amoxicillin/clavulanate resistance at the University
      Hospital of the West Indies 1994 versus 2003.

PMID- 18072422
TI  - [Endoscopic changes in the stomach and duodenal mucosa caused by microdose
      acetylsalicylic acid therapy and their prevention--editorial].

PMID- 18072423
TI  - [Rituximab (antiCD20 monoclonal antibody) and molecular-biological negativity in
      the treatment of patients with follicular lymphoma--a way to a cure?--Editorial].

PMID- 18072424
TI  - [Pulmonary alveolar proteinosis--the past and the present--editorial].

PMID- 18072425
TI  - [Drug-eluting stents--for all, for some or for none?--Editorial].

PMID- 18072426
TI  - [Changes in lipid metabolism in patients in the active phase of Crohn's disease].
AB  - INTRODUCTION: Crohn's disease (CD) in its active period is accompanied by a
      decreased food intake and deterioration in water, mineral and metabolic balance.
      Lipid metabolism is known to be altered in many acute diseases, and
      hypocholesterolemia is a serious negative prognostic indicator. The causes of
      decreased serum cholesterol concentration are multiple. Simultaneous affection of
      both cholesterol synthesis and absorption has been reported in many sources. The
      changes in both the above processes can be quantified with the use of specific
      indicators of synthesis (cholesterol level) and absorption (sitosterol and
      campesterol levels). OBJECTIVE: The objective of the study was to demonstrate
      changes in lipid metabolism in patients with active Crohn's disease, and to find
      out to what extent the above phenomenon is influenced by the affection of the
      process of cholesterol synthesis and/or absorption in the case of detected
      hypocholesterolemia. MATERIAL AND METHODS: Total serum cholesterol, LDL- and HDL
      cholesterol and triglyceride levels were measured on the 3rd, 14th and 28th day
      from admission in addition to admission analyses in 24 patients with acute
      manifestation of CD (CDAI - Cohn's disease activity index - over 150). Also
      measured were the concentrations ofsqualene, lathosterol, sitosterol and
      campesterol. The results were compared with a control sample of 100 voluntary
      blood donors. The obtained data was processed using the Sigma-stat 3.1
      statistical software. RESULTS: Decreased levels of all basic lipid metabolism
      parameters were detected. At the same time, a statistically significant decrease
      in the levels of lathosterol and camposterol was recorded. The decrease in
      sitosterol levels was insignificant and the level of squalene was higher than in
      the controls. CONCLUSION: Significant changes in lipid metabolism were
      demonstrated in the study in patients in active phase of Crohn's disease. Also
      detected was statistically significant hypocholesterolemia, with altered process
      of cholesterol synthesis and absorption.

PMID- 18072427
TI  - [Cortisol levels are more closely associated with depressiveness and other
      psychopathologies than catecholamine levels].
AB  - OBJECTIVE: Quantification of changes in the levels of the above hormones, i.e.
      cortisol, adrenalin, noradrenalin and dopamine depending on the presence of
      depressive symptoms and other psychopathological symptoms. SAMPLE: 259 randomly
      selected individuals from the population of the city of Pilsen. METHOD: Zung self
      assessment scale and SCL-90 questionnaire were used to assess depressiveness and
      other psychopathologies. Serum cortisol levels were measured, as well as the
      levels ofcortisol and catecholamine (adrenalin, noradrenalin and dopamine) in a
      24-hour urine sample. The studied sample was divided, by an arbitrarily defined
      limit, into a group with a higher and a group with a lower excretion of the
      monitored hormones. RESULTS: The group with cortisol excretion higher than 300
      nmol/24 h had a significantly higher score in terms of the SCL-90 questionnaire
      interpersonal sensitiveness, depression, anxiety, phobia, paranoidism and
      psychoticism as compared with the group with cortisol excretion below 300 nmol/24
      h (p < 0.05). The group with cortisol excretion above 300 nmol/24 h had also a
      significantly higher score on Zung's self-assessment depression scale as compared
      with the group with cortisol excretion below 300 nmol/24 h (p < 0.05). Division
      of the sample according to the score on Zung's self-assessment depression scale
      (SDS index > or = 50) has shown that women with a record of depressive symptoms
      had a statistically significant higher of urinary cortisol excretion in 24 hours
      (average 219.40 as compared with 191.64 nmol/24 h, respectively, p = 0.02). The
      group of men with depressive symptoms according to the score obtained on Zung
      self-assessment scale only showed a trend towards higher urinary noradrenalin
      excretion in 24 hours (average of 69.77 as compared with 63.84 microg/24 h, p =
      0.17). CONCLUSION: As shown by the above results, there is a link between 24-hour
      urinary cortisol excretion levels and the monitored parameters of psychic
      condition.

PMID- 18072428
TI  - [Our experience in continuous administration of insulin using infusion dispenser
      at a metabolic intensive care unit (MICU)].
AB  - INTRODUCTION: The article summarises the experience of the authors in the
      administration of insulin using an infusion dispenser at a metabolic intensive
      care unit (MICU) both to patients with decompensated diabetes mellitus and to
      patients admitted with a sepsis or other life-threatening condition of internal
      nature. PATIENTS AND RESULTS: Insulin was administered with the use of a
      dispenser to a total of 50 patients during 6 months of 2005. 13 of those patients
      showed signs of ketoacidotic or hyperosmolar coma in the course of diabetes
      mellitus. All of these patients were compensated within 24 hours and transferred
      to a standard ward for further treatment within 48 hours. 37 patients were
      admitted in a critical condition, the cause ofwhich was sepsis and a serious
      internal disease in 29 and 8 patients, respectively. 12 of the patients died
      during their hospitalisation at MICU, of which 8 in the first 3 days after
      admission. No significant correlation between the age, diabetes mellitus
      diagnosis or an associated cardiovascular morbidity and the death at MICU was
      discovered, but there was a very close ling between the mortality at the
      intensive care unit and the baseline blood level of C-reactive protein (160 mg/l;
      32-352 in the patients who died, and 111 mg/l 15-168 in the patients who
      survived), p < 0.01. Glycaemia at admission did not differ significantly for the
      patients who dies and those who survived, but average glycaemia for all three
      measurements at MICU was significantly higher in the patients who died (10.4
      mmol/l; 6.2-22.4) as compared with those who survived (7.8 mmol/l; 5.8-16.6), p <
      0.01. The time of insulin administration was significantly shorter in patients
      who died (3.3 days; 1-6) as compared with those who survived (5.2 days; 3-10), p
      < 0.01. There was no significant difference between hourly insulin dose in the
      patients who died (2.8 j/hour; 0.6-8.6) and in those who survived (2.6 j/hour;
      0.8-7.6). A trend towards lower mortality was recorded for the group of patients
      with average glycaemia below 8 mmol/l and/or those in whom glycaemia mostly
      ranged between 4.4 and 8.0 mmol/l, but the difference was not statistically
      significant. A significantly lower consumption of insulin was recorded for the
      patients with average glycaemia below 8 mmol/l and/or those whose glycaemia
      measurements mostly ranged between 4.4 and 8.0 mmol/l. Hypoglycaemia defined as
      glycaemia below 4.4 mmol/l was present in 2% of all measurements, in 11 patients
      on the total, and their results were not significantly associated with mortality
      at MICU. CONCLUSION: Mortality of patients admitted with sepsis or other life
      threatening condition of internal nature was significantly higher in the group of
      patients with higher average glycaemia among all the measurements performed at
      MICU. In patients who died, the total time of insulin administration was
      significantly shorter, but there was no difference between the average hourly
      insulin dose in the group of the patients who died and those who survived.

PMID- 18072429
TI  - [Endoscopic changes in the stomach and duodenal mucosa caused by minidose
      acetylsalicylic acid therapy and their prevention].
AB  - Minidose acetylsalicylic acid (ASA) administration is a significant risk factor
      for changes in the stomach and duodenal mucosa also in persons whose anamnesis
      does not indicate any previous symptoms of stomach disease or any other risk
      factor. One month ASA minidose therapy provoked changes in the stomach and
      duodenal mucosa in 43.7% of persons receiving the therapy for cardiologic or
      neurologic indications. The changes primarily involved erosion and were mainly
      located on the stomach mucosa, without signs of active bleeding. If ASA minidose
      therapy was administered for 1 month together with the proton pump inhibitor
      omeprazole, the rate of incidence of changes detected in the mucosa was
      statistically significantly lower, i.e. only 27.6 %, again without signs of fresh
      bleeding. The presence of Heliobacter pylori probably does not play a critical
      role; Heliobacter pylori was only detected in 34.1% of patients with changes in
      the mucosa. The persons who need ASA minidose therapy and especially those with
      risk factors must be secured by drugs with protective effect on the stomach and
      duodenal mucosa during ASA therapy, specifically in the form of proton pump
      inhibitors. Considering the benefit and complications of low-dose ASA therapy, it
      should not be indicated to persons with a low risk of cardiovascular or
      cerebrovascular complications and should be reserved for the treatment of high
      risk patients.

PMID- 18072430
TI  - [Achieving Bcl-2/IgH negativity in peripheral blood/bone marrow after therapy
      implies better prognosis for patients with follicular lymphoma].
AB  - Bcl-2/IgH rearrangement is a characteristic molecular rearrangement in patients
      with follicular lymphoma (FL), yet its prognostic significance is still unclear.
      OBJECTIVE: Evaluation of the implications of achieving Bcl-2/IgH negativity for
      the prognosis of FL patients. Twenty seven patients (54%) were receiving only
      chemotherapy (CHT), 23 patients (46%) were receiving chemotherapy combined with
      monoclonal antibody anti/CD20, rituximab (R-CHT). RESULTS: Molecular genetic
      remission was achieved in 7 out of 11 patients (64%) after R-CHT, and only in 2
      out of 14 patients (14%) after CHT- this difference was statistically significant
      (p = 0.037). 4 weekly doses of rituximab were administered in a sequence to 17
      out of 27 patients who had received only chemotherapy and failed to achieve
      complete remission. 12 out of 17 patients (71%) on this therapy were Bcl-2/IgH
      positive prior to treatment. 7 out of 12 (58 %) patients were no longer Bcl-2/IgH
      positive in a check performed after one month; the remaining 2 out of 5 patients
      had a negative Bcl-2/IgH record for the interval of 3 months (1 patient) or 6 (1
      patient) months, respectively. The following factors were associated with the
      achievement of Bcl-2/IgH negativity at any point during the treatment: age < 65
      years (p = 0.02) and performance status 0 + 1 according to WHO at baseline (p =
      0.02). Patients who were Bcl-2/IgH negative after treatment had a lower
      recurrence/progression risk rate than the Bcl-2/IgH positive group of patients,
      i.e. 27% vs. 75% (p = 0.03), and a higher chance for progression-free survival,
      i.e. 81% vs. 38% (p = 0.004), event-free survival, i.e. 74% vs. 38% (p = 0.01),
      and overall survival, i.e. 87% vs. 74% (p = 0.05) at 2 years. CONCLUSION: In our
      experience, achieving Bcl-2/IgH negativity after follicular lymphoma therapy
      implies a better prognosis.

PMID- 18072431
TI  - [The impact of statin therapy on bone density changes in postmenopausal women].
AB  - Generalised use of statins in primary and secondary prevention of ischemic heart
      disease has led in recent years to the discovery ofa number of other
      "pleiotropic" effects ofstatins. One of them is the effect ofstatins on bone
      metabolism. The objective of the study was to monitor bone density, bone turnover
      markers and basic biochemical parameters in a group of postmenopausal women at
      regular intervals for a period of 2 years. The monitoring allowed for an
      assessment of the effect of statin therapy on those parameters. Statin therapy
      safety was also monitored. According to expectations, the group receiving active
      treatment recorded a decrease in the levels of total cholesterol, as well as LDL
      cholesterol, and a mild decrease in the level of triacylglycerols. However, no
      significant difference in bone density in any of the measured regions (NECK,
      TROCH, SHAFT) was found when the trends in bone density parameters were compared
      for the two groups, nor there was a significant change in the respective T
      scores. There was no significant difference with respect to the markers of bone
      formation or the markers of bone resorption between the group with active
      treatment and the control group. The results correspond to inconsistent data from
      the performed and quoted retrospective and prospective studies.

PMID- 18072432
TI  - [Analysis of the effect of circadian rhythm on the heart rate turbulence in
      patients without evidence of organic heart disease].
AB  - Some studies have demonstrated circadian incidence of sudden cardiac death (SCD),
      ventricular ectopies, acute coronary syndromes and heart rate variability. One of
      new parameters applied in non-invasive stratification of sudden cardiac death is
      heart rate turbulence (HRT). Detection of circadian oscillations in HRT and
      optimised measurement of HRT can increase the positive predictive value of HRT as
      a sign of SCD risk. The set consisted of 48 patients in a sequence order aged 45
      +/- 12 years (of which 23 men and 25 women), indicated for Holter monitoring
      ofventricular ectopies who had good left ventricular function with LV EF 0.53 +/-
      0.11. HRT was measured in two-hour intervals within a 24 hour period, followed by
      an analysis of circadian dependence of HRT. A significant circadian oscillation
      in the TS (turbulence slope) parameter was recorded. No circadian signs were
      detected for the TO (turbulence onset) parameter. The project is supported by
      grant no. NR/8478-3.

PMID- 18072433
TI  - [Pulmonary alveolar proteinosis].
AB  - Pulmonary alveolar proteinosis is a rare disease characterised by excessive
      accumulation of surfactant components in the alveoli and the distal airways with
      minimum inflammatory reaction and fibrosis of pulmonary interstitium. Three
      clinical forms of pulmonary alveolar proteinosis are distinguished - congenital,
      primary and secondary. Results of ultrastructural, biochemical and functional
      analyses and studies performed on genetically modified mice support the
      presumption that accumulation of surfactant in pulmonary alveolar proteinosis is
      a result of a degradation disorder and of diminished clearance of the surfactant
      from the alveolar space rather than of excessive synthesis of surfactant
      components. Over the last 15 years, significant discoveries have been made which
      have helped to clarify the etiology and pathogenesis of the disease. A number of
      gene mutations have been discovered which lead to the development of congenital
      pulmonary proteinosis. Apart from impaired surfactant protein function, a key
      role in the development of pulmonary alveolar proteinosis is played by the signal
      pathway of granulocyte and macrophage colonies stimulating growth factor (GM-CSF)
      which is necessary for the functioning of alveolar macrophages and for surfactant
      homeostasis. The role of GM-CSF has been proven especially in primary pulmonary
      alveolar proteinosis which is currently considered an auto-immune disease
      involving the development of GM-CSF neutralising autoantibodies. In most cases,
      the prognosis for the disease in adult patients is good, even though there is a
      10 to 15% rate of patients who develop respiratory failure. Total pulmonary
      lavage is considered to be the standard method of treatment. In recent years,
      recombinant human GM-CSF has been studied as a prospective therapy for the
      treatment of pulmonary alveolar proteinosis.

PMID- 18072434
TI  - [Late coronary stent thrombosis and clopidogrel].
AB  - The existence of late coronary stent thrombosis is a topical issue in cardiology
      today. The synoptic article discusses current definition of the above phenomenon,
      its delimitation in time and actual incidence. Based on data from available
      observation and randomised studies, long-term safety of conventional bare metal
      and drug-eluting stents is evaluated, as well as the safety profile following
      implantation. The length of thienopyridin treatment after percutaneous coronary
      intervention (PCI) varies according to the type of stent used. While a
      conventional bare metal stent (BMS) implant provides long-term safety with one
      month treatment, the implantation of a drug-eluting stent (DES) should be
      complemented with a 12-month period of clopidogrel administration. This approach
      may be in the future influenced by further progress in drug-eluting stents
      development and by prospectively acquired information on long-term administration
      of clopidogrel to such patients.

PMID- 18072435
TI  - [The MIAC (malnutrition, inflammation, atherosclerosis, calcification) syndrome].
AB  - The number of patients with chronic renal failure is on the rise; these patients
      have a 10 to 20 times higher risk of development and progression of
      cardiovascular diseases. Higher cardiovascular risk in such patients cannot be
      satisfactorily explained by traditional risk factors defined in the Framingham
      study. On the contrary, a concept of reverse epidemiology has been brought
      forward, designating a situation in which the incidence of obesity and
      hyperlipoproteinemia is associated with a higher survival rate of the patients
      concerned. Higher risk is today explained by the "MIAC (malnutrition,
      inflammation, atherosclerosis, calcification) syndrome", which is present in
      patients with chronic kidney disease. New evidence has been recently obtained of
      different circulating molecules associated with atherosclerosis, the plasmatic
      levels of which are decreased or increased in such patients and which are in a
      way linked with the MIAC syndrome and the progression of atherosclerosis.
      Clinical management of the syndrome could increase survival in the future, and
      reduce morbidity and the number of hospitalisations. Circulating molecules could
      serve as markers evidencing the presence of the syndrome and its severity, as
      well as the success of treatment.

PMID- 18072436
TI  - [Pseudomembranous colitis].
AB  - For some thirty years it has been known that pathologic proliferation oftoxigenic
      Clostridium difficile may lead to inflammation of colonic mucosa which, in its
      fully developed form, manifests as pseudomembranous colitis. CDAD (Clostridium
      difficile - Associated Disease or Diarrhoea) is the term which is generally and
      quite aptly used for the disease in literature on the subject. In most cases, the
      disease develops after the administration of broad-spectrum antibiotics, yet
      there are also other important pathogenetic factors involved which should not be
      ignored. The disease has grown in significance over recent years due to the
      occurrence of serious epidemics in a number of advanced countries provoked by a
      highly virulent strain characterised as ribotype 027, toxinotype III, pulsovar
      NAP1. CDAD is a potentially fatal disease, yet it can be effectively cured if
      diagnosed on time. Stool toxin testing plays a crucial role in the diagnostics of
      the disease, and the use of endoscopy has been on the rise. Administration of
      targeted antibiotics is of critical importance for successful therapy,
      metronidazol or orally administered vankomycine being considered the most
      reliable, and there are also other drugs with promising effects. However, the
      rate of recurrence of the disease is as high as 25%. In view of the realistic
      threat of propagation of the highly virulent strain in the territory of the Czech
      Republic, preparations have started for the setting up of a national reference
      laboratory for Clostridium difficile typification.

PMID- 18072437
TI  - [Incretin strategy in the treatment of type 2 diabetes mellitus--the DPP-IV
      inhibitor sitagliptin].
AB  - Sitagliptin, distributed under the brand name of Januvia, has been the first and
      so far the only dipeptidyl peptidase IV (DPP-IV) inhibitor introduced in clinical
      practice. The results of published clinical studies clearly demonstrate its
      effectiveness and safety as an oral antidiabetic. Apart from increasing the
      insulin level, Sitagliptin reduces the level ofglucagon. The principal advantages
      of Sitagliptin from the clinical point of view are: a) the ability to reduce both
      fasting and non-fasting glycaemia and improve the HbA(1c) values, b) the fact
      that it does not provoke weight increase, c) the fact that the risk of
      hypoglycaemia is significantly lower as compared with sulfonylurea derivatives,
      d) good tolerability.

PMID- 18072438
TI  - [The benefit from ibandronate in the treatment of postmenopausal osteoporosis].
AB  - Apart from other factors, the treatment of osteoporosis is limited by a narrow
      range of applicable drugs. Ibandronate, forming part of the aminobisphosphonate
      group, which was launched in clinical practice in 2005, has extended the range of
      treatment options. It allows for intermittent dosage in 1-month (oral form) or 3
      month (intravenous form) intervals, whilst the high efficiency of treatment and
      good safety profile are preserved. Intermittent dosage significantly improves the
      adherence of patients to treatment, which has, apart from other advantages, a
      positive effect on cost efficiency of treatment. In addition, oscillation in bone
      remodelation in the course of intermittent ibandronate treatment might have a
      positive effect on the physiology of bone tissue, thus reducing some risks
      associated with bisphosphonate treatment.

PMID- 18072439
TI  - [Chronic benign exsudative pericarditis--a case of familiar incidence].
AB  - Pericarditis is a common disease caused by a number of factors. Chronic
      pericarditis is defined as the presence of pericardial effusion for more than 3
      or 6 months. The case study reports a case of familiar incidence of chronic
      exsudative pericarditis in a young woman, her sister and her mother, with an
      analysis of diagnostic and therapeutic options. According to available
      literature, this is the second case described of such form of familiar incidence.

PMID- 18072440
TI  - [Results of the ADVANCE study].

PMID- 18072441
TI  - Management of adult incisional hernias at the University of Maiduguri Teaching
      Hospital.
AB  - BACKGROUND: Incisional hernias (IH) represent a breakdown or loss of continuity
      of a fascial closure. They are thus unique as the only external wall hernias that
      are iatrogenic in aetiology. Incisional hernias are not uncommon complications of
      laparotomy closure with reported incidence of 2 to 11%. OBJECTIVES: To review our
      experience,with incisional hernaia identify possible risk factors and proffer
      preventable strategies. PATIENTS AND METHODS: All case records of adult patients
      managed with IH at the University of Maiduguri Teaching Hospital between January
      1995 and December 2004 were retrieved from the Medical Records Department.
      Relevant data on age, sex, type and institution of index surgery (General
      Hospital or Private Hospital), premorbid factors, type of repair, post-operative
      complications were extracted. Case records with inadequate information were
      excluded. RESULTS: Between January 1995 and December 2004 a total of 440 patients
      with external abdominal hernias were treated at UMTH. Out of these: 38 (11.6%)
      were Incisional hernias and form the basis of this study. Their ages ranged
      between 18 and 80 years, with peak age range of 40-49 years. There were 6 males
      and 32 females giving a male to female ratio of 1:5.3. The commonest index
      surgeries were caesarean section in 12 patients (31.6%) and appendicectomy 10
      patients (26.3%). Of the index surgeries 26 (68.4) and 10 (26.3) were performed
      in general and private hospitals respectively. Only 2(5.3%) were done at UMTH.
      Wound sepsis, in 18 patients (47.4%), postoperative cough, 8 (21.1%) and obesity
      6 (15.8%) were the commonest risk factors. Poor surgical technique was found in
      36 patients (94.7%) Most of the patients presented late; 8(21.1%) with recurrence
      and 6(15.8%) were giant in size. All but one were successfully repaired. Only one
      (2.3%) had recurrence. There was no mortality. CONCLUSIONS: Incisional hernias
      are not uncommon constituting 11.6% of all adult external abdominal wall hernias
      repaired at UMTH. Most of the causes are preventable with 94.7% of the index
      surgery done at peripheral hospitals where poor surgical technique was common to
      all. There is urgent need to re-train our general duty doctors on proper surgical
      techniques of abdominal wound closure.

PMID- 18072442
TI  - An audit of perioperative cardiac arrest at Lagos University Teaching Hospital.
AB  - OBJECTIVE: Intraoperative cardiac arrests are not uncommon and are related to
      both surgical and anaesthetic factors. This study aimed to examine the factors
      which predispose to a periopeartive cardiac arrest, to assess the appropriateness
      of therapy and the outcome. MATERIALS AND METHODS: All perioperative cardiac
      arrests in adults that occurred in a one year period(January 2003 to December
      2003) at the Lagos University Teaching Hospital were prospectively studied. All
      patients less than 16 years and cardiac arrests occurring outside the direct
      supervision of the anaesthetists were excluded. Study variables included
      demographic data, ASA score, urgency of surgery, surgical procedure, aetiology,
      time and duration of arrest, cardiac arrest rhythm, management as well as
      immediate outcome and survival to hospital discharge. RESULTS: Thirteen cardiac
      arrests occurred in 2147 cases (incidence of 6 per 1000). The mean age of
      patients was 30.23 +/- 11.06 years. Ten patients had anASA score greater than 3.
      Hypovolaemia was responsible for arrests in 9 patients. Two arrests occurred at
      induction, 7 intraoperatively and 4 postoperatively. Seven patients had non-VF/VT
      rhythms. Cardiopulmonary resuscitation was instituted immediately. The mean
      duration of arrest was 25.66 +/- 13.34 minutes. Drug and defibrillator therapy
      were inadequate. Immediate survival occurred in 5 patients (38.46%). Factors
      associated with significant difference in recovery from a cardiac arrest were
      type of surgery (p=0.043) and duration of resuscitation (p=0.022) CONCLUSION:
      Majority of cardiac arrests were due to hypovolaemia from massive blood loss.
      There is a need for the provision of adequate banked blood as well as improvement
      in training in the management of in-hospital cardiac arrest to ensure a better
      outcome.

PMID- 18072443
TI  - Infant feeding practices among mothers delivered at the Jos University Teaching
      Hospital intending to breastfeed exclusively for six months.
AB  - OBJECTIVE: The practicability of excusive breastfeeding (EBFing) for 6 months by
      mothers, especially the employed ones, in this country has been a big question to
      answer considering the short duration of their maternity leave of 3 months around
      their delivery. Using WHO recommendation as a point of reference, the present
      study assessed the infant feeding practices of mothers delivered at Jos
      University Teaching Hospital, (JUTH). Emphasis was moved on the employed ones.
      METHOD: Infant feeding practices was studied prospectively among 461 mothers who
      delivered in JUTH and who initially intended to breastfeed exclusively for 6
      months. RESULT: Four hundred and twenty two (91.5%) of the recruited mothers
      continued EBFing practice for 6 months, while 25 (5.4%) dropped out from the
      practice before 6 months. Formular feed was introduced by 5 (1.1%), water by
      13(2.8%), while 7 (1.5%) babies were started on solid and semi-solid feeds before
      6 months. Seventy six of the eight-two (92.7%) employed mothers continued EBFing
      practice for up to 6 months. Government employed counterpart (96.6%vs 64.0%), so
      also was primigravidae more than the grand-multigravidae (97.4% vs 80.0%). EBFing
      was also practiced most by house wives (98.1%) and petty traders (93.9%), and
      least practiced by business women and students mothers (67.9%) and (51.9%). No
      significant difference was observed in EBFing practice among mothers from
      different socio-economic background (92.9%,95.4% and 94.4%) for upper, middle and
      lower socio-economic class (SEC), and between male and female infants (50.4% Vs
      49.6%), P > 0.05.

PMID- 18072444
TI  - Discharge of hospitalized under-fives against medical advice in Benin City,
      Nigeria.
AB  - OBJECTIVE: To determine the incidence of discharge against medical advice (DAMA)
      among under-fives in Benin City, document reasons for these discharges and
      suggest ways of reducing its occurrence. METHODS: The admissions and discharges
      registers as well as the case-notes of all children aged between one and fifty
      nine months admitted over a two-year period were retrospectively examined. The
      data obtained included sex, age, main diagnosis, signatories to the discharge
      documents and reasons/circumstances for DAMA. RESULTS: Of the 1017 under-fives
      admitted, 58 (5.7%) were DAMA with a higher prevalence in girls (7.4%) than in
      boys (4.2%) p>0.05. The incidence of DAMA (9.7%) was highest among children aged
      24-35 months. About half (51.7%) of the parents of children DAMA either did not
      have formal education or failed to complete primary education. Thirty seven
      (63.8%) of parents of children DAMA belonged to social classes IV and V. The
      fathers were the signatories to the discharge documents in 65.5% and the mothers
      in only 5.2% of cases. Within 24-48 hours after DAMA, 20.7% of cases were re
      admitted. Parental fear of accumulation of hospital bills was the commonest
      reason for DAMA. Mean duration of hospital stay was 3.1 days. CONCLUSION:
      Discharge of hospitalised under-fives against medical advice is a common social
      paediatric problem with gender differentials in its incidence. We believe that
      with improvement in the socio-economic status of our parents the incidence of
      DAMA will be greatly reduced.

PMID- 18072445
TI  - Contraceptive choices among women in Zaria, Nigeria.
AB  - AIMS/OBJECTIVE: To study the choice of contraceptive usage and the factors
      responsible for such choices in northern Nigeria. DESIGN: A cross-sectional
      study. SETTING: Ahmadu Bello University Teaching Hospital, Zaria, Nigeria.
      SUBJECTS: New clients attending the reproductive health centre. MAIN OUTCOME
      MEASURES: Choice of contraceptive, reason for choice, knowledge and source of
      knowledge about contraceptives. RESULTS: Four hundred and eighteen clients were
      interviewed. Three hundred and seventy two (89%) knew at least one method of
      contraception; 50.7% used injectable contraceptives, 22.5% intrauterine
      contraceptive devices, 13.9% Norplant and 10.3% oral contraceptive pills. One
      hundred and forty four (34.5%) were referred by midwives and 25.6% by other
      nurses. CONCLUSIONS: The most commonly used contraceptive in our environment is
      the injectable method.

PMID- 18072446
TI  - Awareness of high blood pressure status, treatment and control in a rural
      community in Edo State.
AB  - A cross-sectional study was carried out in Udo, a rural community in Ovia South
      west LGA of Edo State to assess the level of awareness of high blood pressure
      status, treatment and control. Cluster sampling method was used to select
      participants and data collection was by researcher administered questionnaire.
      Blood pressure measurement was by standardized method. A total of 590 respondents
      with mean age 30.7 +/- 14.6 years participated in the study. The prevalence of
      hypertension was 20.2% using the WHO/ISH criteria of SBP > or = 140 mmHg and/or
      DBP > or = 90 mmHg. Twenty two (18.5%) of the hypertensives were aware of their
      high blood pressure status. Awareness was higher in females, increased with age
      and decreased with higher educational status. Of those aware of their condition,
      77.3% were on treatment and ofthese, 29.4% had adequate blood pressure control.
      This study has revealed a low level of awareness of high blood pressure status
      and control in this rural community. Therefore, there is urgent need for regular
      community-based hypertension screening programmes.

PMID- 18072447
TI  - Serum antiphospholipid antibodies among healthy adults in northeastern Nigeria.
AB  - BACKGROUND: Antiphospholipid antibodies have been associated with variety of
      conditions. There is no standard health associated reference values required for
      the interpretation of antiphospholipid antibodies result available among adults
      in North- eastern Nigeria and Nigeria in general. The aim of this study is to
      determine the normal serum level (cutoffpoint) in healthy adult Nigerians. The
      need or otherwise for stratification of the reference values by sex would also be
      determined. METHODS: Seventy-six healthy adults' medical students and health
      workers were enrolled in the study over the period of twelve consecutive months.
      Blood samples were taken for quantification of antiphopholipid antibodies using
      Enzyme Linked Immunosorbent Assay (ELISA) technique. Apparently healthy adults
      age between 16-50 years who are neither human immunodeficiency virus positive nor
      VDRL positive were included in the study. Reference values were calculated by
      parametric method. RESULTS: The mean serum concentration of IgG Antia2GP1 for the
      sample population was 21.43 +/- 9.43 U/ml. The mean serum concentration of IgG
      Antia2GP1 for males was 18.6 +/- 7.6 U/ml while for the female sample population
      was 22.7+/-10.2 U/ml. There is no gender variation (P > 0.05). CONCLUSION: The
      reference value for serum antiphospholipid antibodies in healthy adults in
      Northeastern Nigeria was 21.43 +/- 9.43 U/ml. The reference values should be used
      in this environment for both sexes. Extension of the scope of the study to cover
      the entire homogenous society of Northern Nigeria is recommended.

PMID- 18072448
TI  - Some characteristics of paediatric admissions at the University of Nigeria
      Teaching Hospital Enugu-Nigeria.
AB  - BACKGROUND: In spite of its limitations, documentation of health facility
      utilization is an aspect of planning for patient care. Information obtained from
      such studies is usually useful in evaluating existing facilities, documenting
      trends in patients needs and improving facilities for patients care. OBJECTIVES:
      To assess the characteristics of children who utilize the services of the
      University Teaching Hospital(UNTH) Enugu for admission and treatment. DESIGN: A
      prospective study of the characteristics of children admitted consecutively over
      an eight month period into the Paediatric medical wards of UNTH was determined
      with the use of a structured questionnaire. RESULTS: Of the three hundred and
      thirty seven children admitted into the wards, aged 5 weeks to 18 years, two
      hundred and five(61%), 78(23%) and 54(16%) belonged to the lower, middle and
      upper social classes respectively. There was a male preponderance (1.3:1) and
      60.5% of the children were less than 5 years of age. The children emergency room
      (CHER) was the route of admission of 214(63.5%) of the children and was
      statistically significant for all social classes (p=0.006). The difference in
      duration of symptoms before presentation in hospital between upper (landII)and
      lower social (IV and V)classes was statistically significant (p=0.005).
      CONCLUSION: The services of this hospital are used mainly by the lower socio
      economic class of the society. There is a delay in presentation of patients even
      to emergency room. The delay in presentation of children to hospital for
      treatment could be due to lack of education or knowledge, economic hardships, and
      absence of health insurance.

PMID- 18072449
TI  - Hypertension among dental patients attending tertiary health institution in Edo
      State, Nigeria.
AB  - INTRODUCTION: Hypertension is one of the cardiovascular diseases which has been
      reported as one of the common causes of death worldwide. Some medical conditions
      including hypertension could alter the course of oral disease; modify dental
      treatment and response to such treatment. OBJECTIVE: This was to determine the
      prevalence of hypertension among dental patients and their common presenting oral
      complaint. METHOD: Measurement of the blood pressure of all the patients aged 18
      77years who were attending the dental clinic was carried out using
      sphygmomanometer and stethoscope. RESULTS: The overall prevalence of hypertension
      among dental patients was 19.7% while that for unknown hypertension (hypertension
      detected at the dental clinic) was 10.3%. Acute periapical periodontitis and
      chronic marginal gingivitis were common clinical presentations. CONCLUSION: Some
      dental patients were unaware of their blood pressure levels. It is important for
      all dental patients to be screened for hypertension to avoid the complications
      that may arise therefrom.

PMID- 18072450
TI  - Patients' perception of obstetric practice in Calabar, Nigeria.
AB  - OBJECTIVE: To determine the influence of patients' perception of obstetric
      practice in Calabar on the low utilization of health facilities for delivery.
      METHODS: The University of Calabar Teaching Hospital, the general hospital and
      eight private clinics in Calabar were visited daily for a period of one month to
      interview postnatal mothers. This was to ascertain the mothers' perception of
      obstetric care in these facilities and their attitude towards some selected birth
      practices. RESULTS: All the interviewed mothers had some formal education, and
      133 (92.4%) were aged 20 years and above. One hundred and forty (97.2%) of the
      mothers were satisfied with at least one aspect of care received. Areas of
      satisfaction mentioned by the mothers include attitude of health staff 114
      (81.4%), clinical care received 85 (60.7%), sanitation of the facility 61
      (43.6%), and basic amenities 47 (33.6%), poor sanitary condition of the health
      facility and lack of basic amenities were the major causes of dissatisfaction.
      Few mothers, 31 (22%) disagreed with dorsal position during second stage of
      labor. Most mothers, 92 (63.9%) would want pain relief in labor; 19 (13.2%) did
      not appreciate shaving of pubic hair and 50 (34.7%) felt episiotomy was not
      necessary for safe delivery. CONCLUSION: To improve the utilization of obstetric
      services in Calabar, basic amenities such as water and sanitation should be
      provided; and there should be restriction of routine birth practices that have no
      evidence of effectiveness.

PMID- 18072451
TI  - A review of preterm admissions into special care baby unit, in University of
      Maiduguri Teaching Hospital: a four year experience.
AB  - There is little or no report of preterm (babies born less than 37 completed weeks
      of gestation) admission from this part of Sahel Savannah of Nigeria. This study
      of four-year period is presented to identify areas that require improvement, such
      as in the Labour ward and neonatal care. The case files of the 428 preterm
      newborns admitted into Special Care Baby Unit (SCBU) of the University of
      Maiduguri Teaching Hospital were reviewed. Preterms constituted 54.9% of the
      overall admissions, 53.4% being Low birth weight newborns (=2500 gm). Premature
      rupture of membrane, previous preterm deliveries, twin gestation and pregnancy
      induced hypertension were some of the common maternal factors that were
      associated with preterm deliveries. Birth asphyxia, Apnoea, Small for gestation
      age 9weight less than 10th centile), respiratatory distress were the main problem
      observed among the preterm newborns. Neonatal mortality rate was 349/1000 live
      birth; 62.1% of the death were preterm infants. Mortalities were common among
      babies weighing 1000 gm or less and also of babies of lower gestational age. We
      can improve on this, by implementing simple common measures such as educating our
      mothers on the need for good antenatal care and hospital deliveries, so that
      those with pregnancy induced hypertension, premature rupture of membrane,
      previous preterm delivery can be detected early and institute proper management.

PMID- 18072452
TI  - Misoprostol use for cervical ripening and induction of labour in a Nigerian
      teaching hospital.
AB  - CONTEXT: Induction of labor is always a challenge to many an obstetrician more so
      when the cervix is unfavorable. OBJECTIVES: To determine the efficacy and safety
      ofmisoprostol in cervical ripening and labour induction. MATERIALS AND METHOD:
      Aprospective study spanning 2 years and involving 151 patients admitted for
      cervical ripening and induction of labor at Usmanu Danfodiyo University Teaching
      Hospital, Sokoto, Nigeria. 50 microgram (mcg) ofmisoprostol was inserted
      vaginally every 4 hours until cervix became favorable or onset of labor. RESULTS:
      Main indications for induction of labour were prolonged pregnancy and
      hypertensive diseases of pregnancy. An average of 2 insertions of 50 mcg tablet
      was used to achieve cervical ripening in 107 patients (71%) and 80% (120) had
      spontaneous labor within 10 hours of insertion. The mean insertion-labor interval
      was 7.86 hours (SD +/- 2.5). The average duration of labour was 9.36 hours (SD +/
      2.9). Vaginal delivery was achieved in 96% of the patients. Uterine
      hyperstimulation occurred in 9 patients but there was no case of uterine rupture.
      CONCLUSION: Misoprostol was effective and safe in cervical ripening and induction
      of labor with a vaginal delivery rate of 96%. It should be an essential drug in
      obstetric practice especially in low resource settings.

PMID- 18072453
TI  - A correlation of symptomatology with nasal smear eosinophilia in non-infectious
      chronic rhinitis preliminary report.
AB  - OBJECTIVE: To correlate subjective and objective clinical features with nasal
      smear cytology findings in noninfectious chronic rhinitis. DESIGN: An analysis of
      prospectively collected data of consecutive patients with non-infectious seasonal
      and perennial rhinosinusitis seen at a tertiary health institution. METHODOLOGY:
      Clinical assessments including Visual Analog Scale (VAS) scoring of presenting
      symptoms of 45 patients suffering from non-infectious chronic rhinosinusitis are
      measured. Subjects had a medical questionnaire regarding presence and duration of
      symptoms, family history of atopy or allergy, occupational exposure to allergens,
      provocative agents, and medication usages. Subjects had detail Ear, Nose, and
      Throat assessment, and nasal secretions were analyzed for eosinophils counts and
      statistically correlated with clinical parameter. RESULT: A total of 45 patients
      were recruited. Age range was 13 to 71 years (SD 11.516). 73% (n=33) were females
      while 27% (n=12) were males. The modal occupation was homemaking (24%, n=11). 38%
      (n=17) had family history of atopy, while 13% (n=6) had family history of
      allergy. Symptoms were perennial in 62% (n=28) and seasonal in 38% (n=17). 9%
      (n=4) of the subjects keep pets at home, while 40% (n=18) grow flowers or trees
      around the house. All subjects gave a history of identifiable provocative agents.
      There is positive correlation of itchy nose with total symptom score. There was
      negative history of occupational exposure to allergens in all subjects. The
      average subjective symptom score are Sneezing (6.3), Itchy nose (6.1), Nasal
      obstruction (6.2) and Runny nose (6.7). There is a high positive correlation of
      sneezing with runny nose (r = 0.51), but poor correlation with nasal obstruction
      (r = 0.15). There is negative correlation of total individual symptom score with
      keeping of pets (r = -0.24) or growing of flowers or trees around house (r = 
      0.039). There is also low correlation of total symptom score with family history
      of atopy (r = 0.06). There is positive correlation of total symptom score with
      number of provocative agents identified (r = 0.34). There is low positive
      correlation of nasal smear eosinophilia with total symptom score (r = 0.030) and
      itchy nose score (r = 0.038). Nasal smear eosinophilia show negative correlation
      with sneezing score (r= -0.076). CONCLUSION: The best predictors of nasal smear
      eosinophilia in non-infectious chronic rhinosinusitis are itchy nose score and
      Individual Total Symptom (ITS) score.

PMID- 18072454
TI  - Aneurysmal bone cyst: a primary or secondary lesion?
AB  - OBJECTIVES: To emphasize the origin of aneurysmal bone cyst as "primary" or
      "secondary" to other lesions of the jaws and 2. Report two cases of the cyst that
      illustrate its controversial origin in the hope that it will add to the
      literature on the subject in Africa. REPORT: Two cases of aneurysmal bone cyst
      occurring in the mandible and maxilla are reported. One of the cysts that
      occurred in a 13-year-old was a primary lesion while the other in a 5-year-old
      was associated with a cementifying fibroma. METHOD: The diagnoses of both lesions
      were confirmed by biopsy. The lesion that occurred in the 13-year-old was treated
      by curettage while the other in the 5-year-old was treated by excision under
      general anaesthesia respectively. RESULT: While the lesion in the 13-year-old was
      haemorrhagic with 'welling up' of blood, the second lesion though haemorrhagic
      was not associated with this phenomenon. Both patients were transfused with 2
      pints and 1 pint of blood respectively. There has not been recurrence of the
      lesions after two years post operatively. CONCLUSION: Aneurysmal bone cyst can
      arise as a primary lesion or associated with a fibro-osseous lesion as
      demonstrated by these two cases. There is a need to serially section biopsy
      specimens of the cyst to detect coexisting lesions.

PMID- 18072455
TI  - Current views on ultrasonography in the management of pyogenic liver abscess
      challenge to practitioners in sub-Saharan Africa.
AB  - The aim of this review of the recent literature on the current practice in the
      management of pyogenic liver abscess (PLA) is to highlight the important roles
      radiological procedures, particularly ultrasonography (US) now play in it. US
      equipment is now widely available in many African nations, yet not much is being
      done to embrace this current line of management. This is evidenced by the dearth
      of published work in this area from especially sub-Saharan Africa. It is being
      suggested that general surgeons and radiologists in this region collaborate more
      to reduce the cost of treating all cases by operations.

PMID- 18072456
TI  - Full-term pregnancy in an incisional hernia--a case report.
AB  - We report a case of full-term pregnancy in a 40 year old woman who presented with
      her fifth pregnancy with the uterus in the incisional hernia sac hanging below
      the groin. She has had previous abdominal operation through a midline scar.
      Complication of the previous operation led to the incisional hernia into which
      she carried a full term pregnancy. Caesarian section and bilateral tubal ligation
      were done with repair of the incisional hernia with nonabsorbable suture with
      uneventful postoperative recovery. It is advised that surgeons carrying out
      abdominal operations for whatever reason, the operations should be done on fit
      patient as much as possible, proper incisions should be made and the fascia
      should be closed with non-absorbable sutures (mass closure) in order to avoid
      occurrence of incisional hernias. Emergency operations in the abdomen including
      caesarian section, surgical principles should always be observed.

PMID- 18072457
TI  - Complex Ebstein's anomaly in a 80 year old Nigerian woman.
AB  - There is a gradually growing interest in the subject of congenital heart diseases
      as many children born with them are now growing into adulthood. The reasons are
      twofold: increasing awareness among clinicians as well as major advances in the
      diagnosis and treatment of congenital heart diseases in children. A case of
      Ebstein's anomaly (EA), one of the most important congenital diseases of the
      tricuspid valve, in an 80 year old woman referred to the cardiology clinic of the
      University of Benin Teaching Hospital in Benin City, Nigeria, is hereby reported.
      It is a rare condition. The features demonstrated in this case report tend to
      suggest that there may be several adult survivors of congenital heart diseases.
      These may coexist with other systemic illnesses such as systemic hypertension.

PMID- 18072458
TI  - Fibular hemimelia: a case report.
AB  - Fibular hemimelia is the congenital absence of the fibula and it is the most
      common congenital absence of long bone of the extremities. Shortening of the
      extremity is obvious at birth with leg-length discrepancy. On plain radiograph of
      the leg and foot, significant fibular deficiency (hypoplasia) or absence of the
      fibula can be seen. In this case report, a 6-month-old baby boy with fibular
      hemimelia is presented. The radiological diagnosis and differential diagnosis are
      discussed. The treatments which include repeated corrective osteotomies and leg
      lengthening surgery are costly and associated with residual deformity.

PMID- 18072459
TI  - Multiple intracranial tuberculomas in an HIV-negative 28 year old male--a case
      report.
AB  - Intracranial tuberculomas are uncommon complications of tuberculosis, especially
      in immuno-competent individuals with no evidence of extra-cranial foci. We report
      a case of an HIV- negative young male who presented with presumed cerebral and
      cerebellar tuberculomas without identifiable extra-cranial focus. The CT scan
      revealed multiple intracranial ring-enhanced lesions. The remarkable response to
      antituberculous drugs and steroid (prednisolone) with near complete resolution of
      clinical and radiological signs was highly suggestive of diagnosis. In the
      differential diagnosis of intracranial mass lesions in sub-Saharan Africa, a high
      index of clinical suspicion is needed to avoid misdiagnosis of intracranial
      tuberculoma.

PMID- 18072460
TI  - Telephone use for surgical follow up in a developing country.

PMID- 18072461
TI  - Awareness, acceptability, and use of male condoms for contraception and
      prevention of sexually transmitted infection among female students in a tertiary
      institution in South Eastern Nigeria.

PMID- 18072462
TI  - Neurological and neuropsychiatry presentation of system lupus erythematosus in
      Black Nigerians.

PMID- 18072464
TI  - [The Er:YAG laser in dentoalveolar surgery].
AB  - In contrast to many currently employed osteotomy techniques like saws or drills
      the use of short-pulsed laser light offers the possibility of non-contact and
      vibration-free bone cutting. With a wavelength of 2.94 microm the Er:YAG laser
      displays a consummate absorption in water and thus is particularly suitable for
      bone ablation. To examine the benefits of laser osteotomy in oral surgery a short
      pulsed Er:YAG laser was used for different surgical procedures in 30 patients.
      Preliminary clinical findings revealed satisfactory cut efficiency and no
      carbonisation. No serious complications were encountered in the postoperative
      wound healing process. However, the surgical procedures were time-consuming.

PMID- 18072463
TI  - Antimicrobial activity of Mahonia aquifolium and two of its alkaloids against
      oral bacteria.
AB  - Extracts or alkaloids isolated from Mahonia aquifolium exhibit antimicrobial
      activity against Gram-positive and Gram-negative bacteria, fungi, and protozoa.
      In this study the bacteriostatic and bacteriocidal activities of a M. aquifolium
      extract and two of its major alkaloids, berberine chloride and oxyacanthine
      sulphate, were tested in vitro against nine different oral bacteria. Minimum
      inhibitory concentrations were in the range from < or = 0.0031% to 0.1993% for
      the M. aquifolium extract, from 0.002% to > 0.125% for berberine chloride, and
      from 0.0156% to > 0.0625% for oxyacanthine sulphate. The values for the minimum
      bactericidal concentrations were in the same range, indicating that the test
      substances most probably acted in a bactericidal manner. The most susceptible
      bacterium against all three test substances was Porphyromonas gingivalis.

PMID- 18072465
TI  - The whole story.

PMID- 18072466
TI  - Bamboozled by biostatistics.

PMID- 18072467
TI  - Decisions, decisions.

PMID- 18072468
TI  - Figures head.

PMID- 18072469
TI  - Number crunchers.

PMID- 18072470
TI  - Antibiotics, por favor.

PMID- 18072471
TI  - Teaching numeracy to physicians-in-training. Quantitative analysis for evidence
      based medicine.
AB  - Many physicians admit to having some degree of innumeracy--difficulty
      understanding and working with numbers. Yet, increasingly, physicians in all
      specialties are committing to practicing evidence-based medicine (EBM) and, as a
      result, must learn to discern quantitative differences and address statistical
      significance. Although no one expects a practicing physician to be able to
      evaluate a statistician's choice of methods or conduct an independent rendering
      of a clinical study's analysis, practitioners of EBM must learn how to assess the
      importance of results found in a clinical study. Since 2001, Mayo Clinic has been
      teaching its residents in pediatric and adolescent medicine the skills required
      for EBM. This article describes the 5 steps involved in practicing EBM, focusing
      on the interpretation of study results.

PMID- 18072472
TI  - The increase of type 2 diabetes mellitus in children.
AB  - Communities around the world have seen a dramatic rise in the incidence of
      childhood obesity and pediatric type 2 diabetes mellitus (T2DM). Although
      significant advancement has been made in our understanding of the pathogenesis
      and risk factors for T2DM in children during the past 15 years, we have yet to
      find the safest and most effective ways to prevent and treat this disease. This
      review highlights our understanding of T2DM in children and outlines treatment
      strategies.

PMID- 18072473
TI  - Keep your eye on the patient.

PMID- 18072474
TI  - Point/counterpoint. Medical physicists should seek employment elsewhere when
      resources are insufficient for quality patient care.

PMID- 18072475
TI  - Reduction of a grid moire pattern by integrating a carbon-interspaced high
      precision x-ray grid with a digital radiographic detector.
AB  - The stationary grid commonly used with a digital x-ray detector causes a moire
      interference pattern due to the inadequate sampling of the grid shadows by the
      detector pixels. There are limitations with the previous methods used to remove
      the moire such as imperfect electromagnetic interference shielding and the loss
      of image information. A new method is proposed for removing the moire pattern by
      integrating a carbon-interspaced high precision x-ray grid with high grid line
      uniformity with the detector for frequency matching. The grid was aligned to the
      detector by translating and rotating the x-ray grid with respect to the detector
      using microcontrolled alignment mechanism. The gap between the grid and the
      detector surface was adjusted with micrometer precision to precisely match the
      projected grid line pitch to the detector pixel pitch. Considering the
      magnification of the grid shadows on the detector plane, the grids were
      manufactured such that the grid line frequency was slightly higher than the
      detector sampling frequency. This study examined the factors that affect the
      moire pattern, particularly the line frequency and displacement. The frequency of
      the moire pattern was found to be sensitive to the angular displacement of the
      grid with respect to the detector while the horizontal translation alters the
      phase but not the moire frequency. The frequency of the moire pattern also
      decreased with decreasing difference in frequency between the grid and the
      detector, and a moire-free image was produced after complete matching for a given
      source to detector distance. The image quality factors including the contrast,
      signal-to-noise ratio and uniformity in the images with and without the moire
      pattern were investigated.

PMID- 18072476
TI  - A rigidity penalty term for nonrigid registration.
AB  - Medical images that are to be registered for clinical application often contain
      both structures that deform and ones that remain rigid. Nonrigid registration
      algorithms that do not model properties of different tissue types may result in
      deformations of rigid structures. In this article a local rigidity penalty term
      is proposed which is included in the registration function in order to penalize
      the deformation of rigid objects. This term can be used for any representation of
      the deformation field capable of modelling locally rigid transformations. By
      using a B-spline representation of the deformation field, a fast algorithm can be
      devised. The proposed method is compared with an unconstrained nonrigid
      registration algorithm. It is evaluated on clinical three-dimensional CT follow
      up data of the thorax and on two-dimensional DSA image sequences. The results
      show that nonrigid registration using the proposed rigidity penalty term is
      capable of nonrigidly aligning images, while keeping user-defined structures
      locally rigid.

PMID- 18072477
TI  - Fast prostate segmentation in 3D TRUS images based on continuity constraint using
      an autoregressive model.
AB  - In this article a new slice-based 3D prostate segmentation method based on a
      continuity constraint, implemented as an autoregressive (AR) model is described.
      In order to decrease the propagated segmentation error produced by the slice
      based 3D segmentation method, a continuity constraint was imposed in the prostate
      segmentation algorithm. A 3D ultrasound image was segmented using the slice-based
      segmentation method. Then, a cross-sectional profile of the resulting contours
      was obtained by intersecting the 2D segmented contours with a coronal plane
      passing through the midpoint of the manually identified rotational axis, which is
      considered to be the approximate center of the prostate. On the coronal cross
      sectional plane, these intersections form a set of radial lines directed from the
      center of the prostate. The lengths of these radial lines were smoothed using an
      AR model. Slice-based 3D segmentations were performed in the clockwise and in the
      anticlockwise directions, where clockwise and anticlockwise are defined with
      respect to the propagation directions on the coronal view. This resulted in two
      different segmentations for each 2D slice. For each pair of unmatched segments,
      in which the distance between the contour generated clockwise and that generated
      anticlockwise was greater than 4 mm, a method was used to select the optimal
      contour. Experiments performed using 3D prostate ultrasound images of nine
      patients demonstrated that the proposed method produced accurate 3D prostate
      boundaries without manual editing. The average distance between the proposed
      method and manual segmentation was 1.29 mm. The average intraobserver coefficient
      of variation (i.e., the standard deviation divided by the average volume) of the
      boundaries segmented by the proposed method was 1.6%. The average segmentation
      time of a 352 x 379 x 704 image on a Pentium IV 2.8 GHz PC was 10 s.

PMID- 18072478
TI  - Dose calculation formalisms and consensus dosimetry parameters for intravascular
      brachytherapy dosimetry: recommendations of the AAPM Therapy Physics Committee
      Task Group No. 149.
AB  - Since the publication of AAPM Task Group 60 report in 1999, a considerable amount
      of dosimetry data for the three coronary brachytherapy systems in use in the
      United States has been reported. A subgroup, Task Group 149, of the AAPM working
      group on Special Brachytherapy Modalities (Bruce Thomadsen, Chair) was charged to
      develop recommendations for dose calculation formalisms and the related consensus
      dosimetry parameters. The recommendations of this group are presented here. For
      the Cordis 192Ir and Novoste 90Sr/90Y systems, the original TG-43 formalism in
      spherical coordinates should be used along with the consensus values of the dose
      rate constant, geometry function, radial dose function, and anisotropy function
      for the single seeds. Contributions from the single seeds should be added
      linearly for the calculation of dose distributions from a source train. For the
      Guidant 32P wire system, the modified TG-43 formalism in cylindrical coordinates
      along with the recommended data for the 20 and 27 mm wires should be used. Data
      tables for the 6, 10, 14, 18, and 22 seed trains of the Cordis system, 30, 40,
      and 60 mm seed trains of the Novoste system, and the 20 and 27 mm wires of the
      Guidant system are presented along with our rationale and methodology for
      selecting the consensus data. Briefly, all available datasets were compared with
      each other and the consensus dataset was either an average of available data or
      the one obtained from the most densely populated study; in most cases this was a
      Monte Carlo calculation.

PMID- 18072479
TI  - The American Board of Radiology Perspective on Maintenance of Certification: Part
      IV: Practice quality improvement in radiologic physics.
AB  - Recent initiatives of the American Board of Medical Specialties (ABMS) in the
      area of maintenance of certification (MOC) have been reflective of the response
      of the medical community to address public concerns regarding quality of care,
      medical error reduction, and patient safety. In March 2000, the 24 member boards
      of the ABMS representing all medical subspecialties in the USA agreed to initiate
      specialty-specific maintenance of certification (MOC) programs. The American
      Board of Radiology (ABR) MOC program for diagnostic radiology, radiation
      oncology, and radiologic physics has been developed, approved by the ABMS, and
      initiated with full implementation for all three disciplines beginning in 2007.
      The overriding objective of MOC is to improve the quality of health care through
      diplomate-initiated learning and quality improvement. The four component parts to
      the MOC process are: Part I: Professional standing, Part II: Evidence of life
      long learning and periodic self-assessment, Part III: Cognitive expertise, and
      Part IV: Evaluation of performance in practice (with the latter being the focus
      of this paper). The key components of Part IV require a physicist-based response
      to demonstrate commitment to practice quality improvement (PQI) and progress in
      continuing individual competence in practice. Diplomates of radiologic physics
      must select a project to be completed over the ten-year cycle that potentially
      can improve the quality of the diplomate's individual or systems practice and
      enhance the quality of care. Five categories have been created from which an
      individual radiologic physics diplomate can select one required PQI project: (1)
      Safety for patients, employees, and the public, (2) accuracy of analyses and
      calculations, (3) report turnaround time and communication issues, (4) practice
      guidelines and technical standards, and (5) surveys (including peer review of
      self-assessment reports). Each diplomate may select a project appropriate for an
      individual, participate in a project within a clinical department, participate in
      a peer review of a self-assessment report, or choose a qualified national project
      sponsored by a society. Once a project has been selected, the steps are: (1)
      Collect baseline data relevant to the chosen project, (2) review and analyze the
      data, (3) create and implement an improvement plan, (4) remeasure and track, and
      (5) report participation to the ABR, using the template provided by the ABR.
      These steps begin in Year 2, following training in Year 1. Specific examples of
      individual PQI projects for each of the three disciplines of radiologic physics
      are provided. Now, through the MOC programs, the relationship between the
      radiologic physicist and the ABR will be continuous through the diplomate's
      professional career. The ABR is committed to providing an effective
      infrastructure that will promote and assist the process of continuing
      professional development including the enhancement of practice quality
      improvement for radiologic physicists.

PMID- 18072480
TI  - The prediction of breast cancer biopsy outcomes using two CAD approaches that
      both emphasize an intelligible decision process.
AB  - Mammography is the most effective method for breast cancer screening available
      today. However, the low positive predictive value of breast biopsy resulting from
      mammogram interpretation leads to approximately 70% unnecessary biopsies with
      benign outcomes. To reduce the high number of unnecessary breast biopsies,
      several computer-aided diagnosis (CAD) systems have been proposed in the last
      several years. These systems help physicians in their decision to perform a
      breast biopsy on a suspicious lesion seen in a mammogram or to perform a short
      term follow-up examination instead. We present two novel CAD approaches that both
      emphasize an intelligible decision process to predict breast biopsy outcomes from
      BI-RADS findings. An intelligible reasoning process is an important requirement
      for the acceptance of CAD systems by physicians. The first approach induces a
      global model based on decison-tree learning. The second approach is based on case
      based reasoning and applies an entropic similarity measure. We have evaluated the
      performance of both CAD approaches on two large publicly available mammography
      reference databases using receiver operating characteristic (ROC) analysis,
      bootstrap sampling, and the ANOVA statistical significance test. Both approaches
      outperform the diagnosis decisions of the physicians. Hence, both systems have
      the potential to reduce the number of unnecessary breast biopsies in clinical
      practice. A comparison of the performance of the proposed decision tree and CBR
      approaches with a state of the art approach based on artificial neural networks
      (ANN) shows that the CBR approach performs slightly better than the ANN approach,
      which in turn results in slightly better performance than the decision-tree
      approach. The differences are statistically significant (p value < 0.001). On
      2100 masses extracted from the DDSM database, the CRB approach for example
      resulted in an area under the ROC curve of A(z) = 0.89 +/- 0.01, the decision
      tree approach in A(z) = 0.87 +/- 0.01, and the ANN approach in A(z) = 0.88 +/-
      0.01.

PMID- 18072481
TI  - Radiological interpretation 2020: toward quantitative image assessment.
AB  - The interpretation of medical images by radiologists is primarily and
      fundamentally a subjective activity, but there are a number of clinical
      applications such as tumor imaging where quantitative imaging (QI) metrics (such
      as tumor growth rate) would be valuable to the patient's care. It is predicted
      that the subjective interpretive environment of the past will, over the next
      decade, evolve toward the increased use of quantitative metrics for evaluating
      patient health from images. The increasing sophistication and resolution of
      modern tomographic scanners promote the development of meaningful quantitative
      end points, determined from images which are in turn produced using well
      controlled imaging protocols. For the QI environment to expand, medical
      physicists, physicians, other researchers and equipment vendors need to work
      collaboratively to develop the quantitative protocols for imaging, scanner
      calibrations, and robust analytical software that will lead to the routine
      inclusion of quantitative parameters in the diagnosis and therapeutic assessment
      of human health. Most importantly, quantitative metrics need to be developed
      which have genuine impact on patient diagnosis and welfare, and only then will QI
      techniques become integrated into the clinical environment.

PMID- 18072482
TI  - A dual-stage method for lesion segmentation on digital mammograms.
AB  - Mass lesion segmentation on mammograms is a challenging task since mass lesions
      are usually embedded and hidden in varying densities of parenchymal tissue
      structures. In this article, we present a method for automatic delineation of
      lesion boundaries on digital mammograms. This method utilizes a geometric active
      contour model that minimizes an energy function based on the homogeneities inside
      and outside of the evolving contour. Prior to the application of the active
      contour model, a radial gradient index (RGI)-based segmentation method is applied
      to yield an initial contour closer to the lesion boundary location in a
      computationally efficient manner. Based on the initial segmentation, an automatic
      background estimation method is applied to identify the effective circumstance of
      the lesion, and a dynamic stopping criterion is implemented to terminate the
      contour evolution when it reaches the lesion boundary. By using a full-field
      digital mammography database with 739 images, we quantitatively compare the
      proposed algorithm with a conventional region-growing method and an RGI-based
      algorithm by use of the area overlap ratio between computer segmentation and
      manual segmentation by an expert radiologist. At an overlap threshold of 0.4, 85%
      of the images are correctly segmented with the proposed method, while only 69%
      and 73% of the images are correctly delineated by our previous developed region
      growing and RGI methods, respectively. This resulting improvement in segmentation
      is statistically significant.

PMID- 18072483
TI  - A method based on moving least squares for XRII image distortion correction.
AB  - This paper presents a novel integrated method to correct geometric distortions of
      XRII (x-ray image intensifier) images. The method has been compared, in terms of
      mean-squared residual error measured at control and intermediate points, with two
      traditional local methods and a traditional global methods. The proposed method
      is based on the methods of moving least squares (MLS) and polynomial fitting.
      Extensive experiments were performed on simulated and real XRII images. In
      simulation, the effect of pincushion distortion, sigmoidal distortion, local
      distortion, noise, and the number of control points was tested. The traditional
      local methods were sensitive to pincushion and sigmoidal distortion. The
      traditional global method was only sensitive to sigmoidal distortion. The
      proposed method was found neither sensitive to pincushion distortion nor
      sensitive to sigmoidal distortion. The sensitivity of the proposed method to
      local distortion was lower than or comparable with that of the traditional global
      method. The sensitivity of the proposed method to noise was higher than that of
      all three traditional methods. Nevertheless, provided the standard deviation of
      noise was not greater than 0.1 pixels, accuracy of the proposed method is still
      higher than the traditional methods. The sensitivity of the proposed method to
      the number of control points was greatly lower than that of the traditional
      methods. Provided that a proper cutoff radius is chosen, accuracy of the proposed
      method is higher than that of the traditional methods. Experiments on real
      images, carried out by using a 9 in. XRII, showed that residual error of the
      proposed method (0.2544 +/- 0.2479 pixels) is lower than that of the traditional
      global method (0.4223 +/- 0.3879 pixels) and local methods (0.4555 +/- 0.3518
      pixels and 0.3696 +/- 0.4019 pixels, respectively).

PMID- 18072484
TI  - High sensitivity radiochromic film dosimetry using an optical common-mode
      rejection and a reflective-mode flatbed color scanner.
AB  - A novel method that can greatly improve the dosimetric sensitivity limit of a
      radiochromic film (RCF) through use of a set of color components, e.g., red and
      green, outputs from a RGB color scanner has been developed. RCFs are known to
      have microscopic and macroscopic nonuniformities, which come from the thickness
      variations in the film's active radiochromic layer and coating. These variations
      in the response make the optical signal-to-noise ratio lower, resulting in lower
      film sensitivity. To mitigate the effects of RCF nonuniform response, an optical
      common-mode rejection (CMR) was developed. The CMR compensates nonuniform
      response by creating a ratio of the two signals where the factors common to both
      numerator and denominator cancel out. The CMR scheme was applied to the
      mathematical operation of creating a ratio using two components, red and green
      outputs from a scanner. The two light component lights are neighboring wavebands
      about 100 nm apart and suffer a common fate, with the exception of wavelength
      dependent events, having passed together along common attenuation paths. Two
      types of dose-response curves as a function of delivered dose ranging from 3.7
      mGy to 8.1 Gy for 100 kV x-ray beams were obtained with the optical CMR scheme
      and the conventional analysis method using red component, respectively. In the
      range of 3.7 mGy to 81 mGy, the optical densities obtained with the optical CMR
      showed a good consistency among eight measured samples and an improved
      consistency with a linear fit within 1 standard deviation of each measured
      optical densities, while those with the conventional analysis exhibited a large
      discrepancy among eight samples and did not show a consistency with a linear fit.

PMID- 18072485
TI  - Initial beam size study for passive scatter proton therapy. I. Monte Carlo
      verification.
AB  - The purpose of this work was to provide an initial validation of a Monte Carlo
      (MC) model of the passive scattering treatment nozzle at the University of Texas
      M. D. Anderson Cancer Center Proton Therapy Center. The MC model included a
      detailed definition of each beam-modifying element in the nozzle, and
      calculations accounted for interactions of the beam with the rotating modulator
      wheel used to create the spread out Bragg peak. In this work we show comparisons
      of calculated dose and fluence profiles with measured data from the nozzle for
      the 250 and 180 MeV beam energies used for patient treatments. Agreement to
      within 1.5 mm of measured data was observed for all MC calculations. The high
      level of agreement between the measurements and the MC model for the two beam
      energies studied provides validation for use of the model in a study of the
      dosimetric effects of the proton beam size and shape at the nozzle entrance.

PMID- 18072486
TI  - Initial beam size study for passive scatter proton therapy. II. Changes in
      delivered depth dose profiles.
AB  - In passively scattered proton radiotherapy, a clinically useful treatment beam is
      produced by spreading a small proton "pencil beam" extracted from the accelerator
      to create both a uniform dose profile laterally and a uniform spread-out Bragg
      peak (SOBP) in depth. Lateral spreading and range modulation of the beam are
      accomplished using specially designed components within the treatment delivery
      nozzle. The purpose of this study was to determine how changes in the size of the
      initial proton pencil beam affect the delivery of dose with a passive scatter
      treatment nozzle. Monte Carlo calculations were used to study changes of the
      beam's in-air energy distribution at the exit of the nozzle and the central axis
      depth dose profiles in water resulting from changes in the incident beam size.
      Our results indicate that the width of the delivered SOBP decreases as the size
      of the initial beam increases.

PMID- 18072487
TI  - A Gaussian mixture model for definition of lung tumor volumes in positron
      emission tomography.
AB  - The increased interest in 18F-fluorodeoxyglucose (FDG) positron emission
      tomography (PET) in radiation treatment planning in the past five years
      necessitated the independent and accurate segmentation of gross tumor volume
      (GTV) from FDG-PET scans. In some studies the radiation oncologist contours the
      GTV based on a computed tomography scan, while incorporating pertinent data from
      the PET images. Alternatively, a simple threshold, typically 40% of the maximum
      intensity, has been employed to differentiate tumor from normal tissue, while
      other researchers have developed algorithms to aid the PET based GTV definition.
      None of these methods, however, results in reliable PET tumor segmentation that
      can be used for more sophisticated treatment plans. For this reason, we developed
      a Gaussian mixture model (GMM) based segmentation technique on selected PET tumor
      regions from non-small cell lung cancer patients. The purpose of this study was
      to investigate the feasibility of using a GMM-based tumor volume definition in a
      robust, reliable and reproducible way. A GMM relies on the idea that any
      distribution, in our case a distribution of image intensities, can be expressed
      as a mixture of Gaussian densities representing different classes. According to
      our implementation, each class belongs to one of three regions in the image; the
      background (B), the uncertain (U) and the target (T), and from these regions we
      can obtain the tumor volume. User interaction in the implementation is required,
      but is limited to the initialization of the model parameters and the selection of
      an "analysis region" to which the modeling is restricted. The segmentation was
      developed on three and tested on another four clinical cases to ensure robustness
      against differences observed in the clinic. It also compared favorably with
      thresholding at 40% of the maximum intensity and a threshold determination
      function based on tumor to background image intensities proposed in a recent
      paper. The parts of the method that are user dependent were evaluated and
      resulted in initial estimates of the method's precision, which is in the order of
      +/-10% of the average tumor volume estimate. With this work we have established
      the applicability of the GMM-based segmentation on clinical studies and we have
      made an initial assessment of the method's precision with respect to tumor volume
      segmentation.

PMID- 18072488
TI  - Dual-energy approach to contrast-enhanced mammography using the balanced filter
      method: spectral optimization and preliminary phantom measurement.
AB  - Dual-energy contrast agent-enhanced mammography is a technique of demonstrating
      breast cancers obscured by a cluttered background resulting from the contrast
      between soft tissues in the breast. The technique has usually been implemented by
      exploiting two exposures to different x-ray tube voltages. In this article,
      another dual-energy approach using the balanced filter method without switching
      the tube voltages is described. For the spectral optimization of dual-energy
      mammography using the balanced filters, we applied a theoretical framework
      reported by Lemacks et al. [Med. Phys. 29, 1739-1751 (2002)] to calculate the
      signal-to-noise ratio (SNR) in an iodinated contrast agent subtraction image.
      This permits the selection of beam parameters such as tube voltage and balanced
      filter material, and the optimization of the latter's thickness with respect to
      some critical quantity-in this case, mean glandular dose. For an imaging system
      with a 0.1 mm thick CsI:T1 scintillator, we predict that the optimal tube voltage
      would be 45 kVp for a tungsten anode using zirconium, iodine, and neodymium
      balanced filters. A mean glandular dose of 1.0 mGy is required to obtain an SNR
      of 5 in order to detect 1.0 mg/cm2 iodine in the resulting clutter-free image of
      a 5 cm thick breast composed of 50% adipose and 50% glandular tissue. In addition
      to spectral optimization, we carried out phantom measurements to demonstrate the
      present dual-energy approach for obtaining a clutter-free image, which
      preferentially shows iodine, of a breast phantom comprising three major
      components-acrylic spheres, olive oil, and an iodinated contrast agent. The
      detection of iodine details on the cluttered background originating from the
      contrast between acrylic spheres and olive oil is analogous to the task of
      distinguishing contrast agents in a mixture of glandular and adipose tissues.

PMID- 18072489
TI  - Determination of prospective displacement-based gate threshold for respiratory
      gated radiation delivery from retrospective phase-based gate threshold selected
      at 4D CT simulation.
AB  - Four-dimensional (4D) computed tomography (CT) imaging has found increasing
      importance in the localization of tumor and surrounding normal structures
      throughout the respiratory cycle. Based on such tumor motion information, it is
      possible to identify the appropriate phase interval for respiratory gated
      treatment planning and delivery. Such a gating phase interval is determined
      retrospectively based on tumor motion from internal tumor displacement. However,
      respiratory-gated treatment is delivered prospectively based on motion determined
      predominantly from an external monitor. Therefore, the simulation gate threshold
      determined from the retrospective phase interval selected for gating at 4D CT
      simulation may not correspond to the delivery gate threshold that is determined
      from the prospective external monitor displacement at treatment delivery. The
      purpose of the present work is to establish a relationship between the thresholds
      for respiratory gating determined at CT simulation and treatment delivery,
      respectively. One hundred fifty external respiratory motion traces, from 90
      patients, with and without audio-visual biofeedback, are analyzed. Two
      respiratory phase intervals, 40%-60% and 30%-70%, are chosen for respiratory
      gating from the 4D CT-derived tumor motion trajectory. From residual tumor
      displacements within each such gating phase interval, a simulation gate threshold
      is defined based on (a) the average and (b) the maximum respiratory displacement
      within the phase interval. The duty cycle for prospective gated delivery is
      estimated from the proportion of external monitor displacement data points within
      both the selected phase interval and the simulation gate threshold. The delivery
      gate threshold is then determined iteratively to match the above determined duty
      cycle. The magnitude of the difference between such gate thresholds determined at
      simulation and treatment delivery is quantified in each case. Phantom motion
      tests yielded coincidence of simulation and delivery gate thresholds to within
      0.3%. For patient data analysis, differences between simulation and delivery gate
      thresholds are reported as a fraction of the total respiratory motion range. For
      the smaller phase interval, the differences between simulation and delivery gate
      thresholds are 8 +/- 11% and 14 +/- 21% with and without audio-visual
      biofeedback, respectively, when the simulation gate threshold is determined based
      on the mean respiratory displacement within the 40%-60% gating phase interval.
      For the longer phase interval, corresponding differences are 4 +/- 7% and 8 +/-
      15% with and without audiovisual biofeedback, respectively. Alternatively, when
      the simulation gate threshold is determined based on the maximum average
      respiratory displacement within the gating phase interval, greater differences
      between simulation and delivery gate thresholds are observed. A relationship
      between retrospective simulation gate threshold and prospective delivery gate
      threshold for respiratory gating is established and validated for regular and
      nonregular respiratory motion. Using this relationship, the delivery gate
      threshold can be reliably estimated at the time of 4D CT simulation, thereby
      improving the accuracy and efficiency of respiratory-gated radiation delivery.

PMID- 18072490
TI  - Improved dynamic-programming-based algorithms for segmentation of masses in
      mammograms.
AB  - In this paper, two new boundary tracing algorithms for segmentation of breast
      masses are presented. These new algorithms are based on the dynamic programming
      based boundary tracing (DPBT) algorithm proposed in Timp and Karssemeijer, [S.
      Timp and N. Karssemeijer, Med. Phys. 31, 958-971 (2004)] The DPBT algorithm
      contains two main steps: (1) construction of a local cost function, and (2)
      application of dynamic programming to the selection of the optimal boundary based
      on the local cost function. The validity of some assumptions used in the design
      of the DPBT algorithm is tested in this paper using a set of 349 mammographic
      images. Based on the results of the tests, modifications to the computation of
      the local cost function have been designed and have resulted in the Improved-DPBT
      (IDPBT) algorithm. A procedure for the dynamic selection of the strength of the
      components of the local cost function is presented that makes these parameters
      independent of the image dataset. Incorporation of this dynamic selection
      procedure has produced another new algorithm which we have called ID2PBT. Methods
      for the determination of some other parameters of the DPBT algorithm that were
      not covered in the original paper are presented as well. The merits of the new
      IDPBT and ID2PBT algorithms are demonstrated experimentally by comparison against
      the DPBT algorithm. The segmentation results are evaluated with base on the area
      overlap measure and other segmentation metrics. Both of the new algorithms
      outperform the original DPBT; the improvements in the algorithms performance are
      more noticeable around the values of the segmentation metrics corresponding to
      the highest segmentation accuracy, i.e., the new algorithms produce more
      optimally segmented regions, rather than a pronounced increase in the average
      quality of all the segmented regions.

PMID- 18072491
TI  - Shielding properties of lead-free protective clothing and their impact on
      radiation doses.
AB  - The shielding properties of two different lead-free materials-tin and a compound
      of 80% tin and 20% bismuth-for protective clothing are compared with those of
      lead for three typical x-ray spectra generated at tube voltages of 60, 75, and
      120 kV. Three different quantities were used to compare the shielding capability
      of the different materials: (1) Air-kerma attenuation factors in narrow-beam
      geometry, (2) air-kerma attenuation factors in broad-beam geometry, and (3)
      ratios of organ and effective doses in the human body for a whole-body
      irradiation with a parallel beam directed frontally at the body. The thicknesses
      of tin (0.45 mm) and the tin/bismuth compound (0.41 mm) to be compared against
      lead correspond to a lead equivalence value of 0.35 mm for the 75 kV spectrum.
      The narrow-beam attenuation factors for 0.45 mm tin are 54% and 32% lower than
      those for 0.35 mm lead for 60 and 120 kV; those for 0.41 mm tin/bismuth are 12%
      and 32% lower, respectively. The decrease of the broad-beam air-kerma attenuation
      factors compared to lead is 74%, 46%, and 41% for tin and 42%, 26%, and 33% for
      tin/bismuth and the spectra at 60, 75, and 120 kV, respectively. Therefore, it is
      recommended that the characterization of the shielding potential of a material
      should be done by measurements in broad-beam geometry. Since the secondary
      radiation that is mainly responsible for the shielding reduction in broad-beam
      geometry is of low penetrability, only more superficially located organs receive
      significantly enhanced doses. The increase for the dose to the glandular breast
      tissue (female) compared to being shielded by lead is 143%, 37%, and 45% when
      shielded by tin, and 35%, 15%, and 39% when shielded by tin/bismuth for 60, 75,
      and 120 kV, respectively. The effective dose rises by 60%, 6%, and 38% for tin,
      and 14%, 3% and, 35% for tin/bismuth shielding, respectively.

PMID- 18072492
TI  - Uniform attenuation correction using the frequency-distance principle.
AB  - The frequency-distance principle (FDP) is a well-known relationship that relates
      the distance between the object and the detector to the slope in the two
      dimensional Fourier transform of the projection sinogram. This relationship has
      been previously applied to compensation of the distance dependent collimator
      blurring in SPECT (single photon emission computed tomography) in the literature.
      This paper makes an attempt to use the FDP to correct for uniform attenuation in
      SPECT. Computer simulations reveal that this technique works well for objects
      consisting of point sources but does not work well for distributed objects.

PMID- 18072493
TI  - Choosing the optimal fit function: comparison of the Akaike information criterion
      and the F-test.
AB  - In many circumstances of data fitting one has to choose the optimal fitting
      function or model among several alternatives. Criteria or tests on which this
      decision is based are necessary and have to be well selected. In this preliminary
      analysis the application of the corrected Akaike information criterion is
      demonstrated considering the example of determining pharmacokinetic parameters
      for the blood serum time activity curves of 111In-labeled anti-CD66 antibody.
      Another model selection criterion, the F-test, is used for comparison. For the
      investigated data the corrected Akaike information criterion has proved to be an
      effective and efficient approach, applicable to nested and non-nested models.

PMID- 18072494
TI  - Hybrid photoacoustic fluorescence molecular tomography using finite-element-based
      inversion.
AB  - Improvements in fluorescence reconstruction when utilizing a hybrid photoacoustic
      (PAT) fluorescence molecular tomography (FMT) method to image optically
      heterogeneous media are studied and showcased. Quantitative optical absorption
      maps are retrieved using a normalized backprojection algorithm for PAT
      reconstruction. Consecutively, the reconstructed absorption distribution is
      employed into computing a diffusion-equation-based forward model for FMT using a
      finite-element solution. The potential promise of the suggested method is
      experimentally verified on tissue-mimicking fluorescent phantoms, where
      improvements in the quality of FMT reconstructions are observed when imaging at
      the presence of a large absorber.

PMID- 18072495
TI  - Fast DRR splat rendering using common consumer graphics hardware.
AB  - Digitally rendered radiographs (DRR) are a vital part of various medical image
      processing applications such as 2D/3D registration for patient pose determination
      in image-guided radiotherapy procedures. This paper presents a technique to
      accelerate DRR creation by using conventional graphics hardware for the rendering
      process. DRR computation itself is done by an efficient volume rendering method
      named wobbled splatting. For programming the graphics hardware, NVIDIAs C for
      Graphics (Cg) is used. The description of an algorithm used for rendering DRRs on
      the graphics hardware is presented, together with a benchmark comparing this
      technique to a CPU-based wobbled splatting program. Results show a reduction of
      rendering time by about 70%-90% depending on the amount of data. For instance,
      rendering a volume of 2 x 10(6) voxels is feasible at an update rate of 38 Hz
      compared to 6 Hz on a common Intel-based PC using the graphics processing unit
      (GPU) of a conventional graphics adapter. In addition, wobbled splatting using
      graphics hardware for DRR computation provides higher resolution DRRs with
      comparable image quality due to special processing characteristics of the GPU. We
      conclude that DRR generation on common graphics hardware using the freely
      available Cg environment is a major step toward 2D/3D registration in clinical
      routine.

PMID- 18072496
TI  - Realtime light dosimetry software tools for interstitial photodynamic therapy of
      the human prostate.
AB  - Photodynamic therapy (PDT) for the treatment of prostate cancer has been
      demonstrated to be a safe treatment option capable of inducing tissue destruction
      and decreasing prostate specific antigen (PSA) levels. However, prostate-PDT
      results in large intra- and interpatient variations in treatment response,
      possibly due to biological variations in tissue composition and short-term
      response to the therapeutic irradiation. Within our group, an instrument for
      interstitial PDT on prostate tissue has been developed that combines therapeutic
      light delivery and monitoring of light transmission via numerous bare-ended
      optical fibers. Here, we present algorithms that utilize data on the light
      distribution within the target tissue to provide realtime treatment feedback
      based on a light dose threshold model for PDT. This realtime dosimetry module is
      implemented to individualize the light dose and compensate for any treatment
      induced variations in light attenuation. More specifically, based on the light
      transmission signals between treatment fibers, spatially resolved spectroscopy is
      utilized to assess the effective attenuation coefficient of the tissue. These
      data constitute input to a block-Cimmino optimization algorithm, employed to
      calculate individual fiber irradiation times provided the requirement to deliver
      a predetermined light dose to the target tissue while sparing surrounding
      sensitive organs. By repeatedly monitoring the light transmission signals during
      the entire treatment session, optical properties and individual fiber irradiation
      times are updated in realtime. The functionality of the algorithms is tested on
      diffuse light distribution data simulated by means of the finite element method
      (FEM). The feasibility of utilizing spatially resolved spectroscopy within
      heterogeneous media such as the prostate gland is discussed. Furthermore, we
      demonstrate the ability of the block-Cimmino algorithm to discriminate between
      target tissue and organs at risk (OAR). Finally, the realtime dosimetry module is
      evaluated for treatment scenarios displaying spatially and temporally varying
      light attenuation levels within the target tissue. We conclude that the realtime
      dosimetry module makes it possible to deliver a certain light dose to the target
      tissue despite spatial and temporal variations of the target tissue optical
      properties at the therapeutic wavelength.

PMID- 18072497
TI  - The GEANT4 toolkit for microdosimetry calculations: application to microbeam
      radiation therapy (MRT).
AB  - Theoretical dose distributions for microbeam radiation therapy (MRT) are computed
      in this paper using the GEANT4 Monte Carlo (MC) simulation toolkit. MRT is an
      innovative experimental radiotherapy technique carried out using an array of
      parallel microbeams of synchrotron-wiggler-generated x rays. Although the
      biological mechanisms underlying the effects of microbeams are still largely
      unknown, the effectiveness of MRT can be traced back to the natural ability of
      normal tissues to rapidly repair small damages to the vasculature, and on the
      lack of a similar healing process in tumoral tissues. Contrary to conventional
      therapy, in which each beam is at least several millimeters wide, the narrowness
      of the microbeams allows a rapid regeneration of the blood vessels along the
      beams' trajectories. For this reason the calculation of the "valley" dose is of
      crucial importance and the correct use of MC codes for such purposes must be
      understood. GEANT4 offers, in addition to the standard libraries, a specialized
      package specifically designed to deal with electromagnetic interactions of
      particles with matter for energies down to 250 eV. This package implements two
      different approaches for electron and photon transport, one based on evaluated
      data libraries, the other adopting analytical models. These features are
      exploited to cross-check theoretical computations for MRT. The lateral and depth
      dose profiles are studied for the irradiation of a 20 cm diameter, 20 cm long
      cylindrical phantom, with cylindrical sources of different size and energy.
      Microbeam arrays are simulated with the aid of superposition algorithms, and the
      ratios of peak-to-valley doses are computed for typical cases used in preclinical
      assays. Dose profiles obtained using the GEANT4 evaluated data libraries and
      analytical models are compared with simulation results previously obtained using
      the PENELOPE code. The results show that dose profiles computed with GEANT4's
      analytical model are almost indistinguishable from those obtained with the
      PENELOPE code, but some noticeable differences appear when the evaluated data
      libraries are used.

PMID- 18072498
TI  - Optimization of reference library used in content-based medical image retrieval
      scheme.
AB  - Building an optimal image reference library is a critical step in developing the
      interactive computer-aided detection and diagnosis (I-CAD) systems of medical
      images using content-based image retrieval (CBIR) schemes. In this study, the
      authors conducted two experiments to investigate (1) the relationship between I
      CAD performance and size of reference library and (2) a new reference selection
      strategy to optimize the library and improve I-CAD performance. The authors
      assembled a reference library that includes 3153 regions of interest (ROI)
      depicting either malignant masses (1592) or CAD-cued false-positive regions
      (1561) and an independent testing data set including 200 masses and 200 false
      positive regions. A CBIR scheme using a distance-weighted K-nearest neighbor
      algorithm is applied to retrieve references that are considered similar to the
      testing sample from the library. The area under receiver operating characteristic
      curve (Az) is used as an index to evaluate the I-CAD performance. In the first
      experiment, the authors systematically increased reference library size and
      tested I-CAD performance. The result indicates that scheme performance improves
      initially from Az= 0.715 to 0.874 and then plateaus when the library size reaches
      approximately half of its maximum capacity. In the second experiment, based on
      the hypothesis that a ROI should be removed if it performs poorly compared to a
      group of similar ROIs in a large and diverse reference library, the authors
      applied a new strategy to identify "poorly effective" references. By removing 174
      identified ROIs from the reference library, I-CAD performance significantly
      increases to Az = 0.914 (p < 0.01). The study demonstrates that increasing
      reference library size and removing poorly effective references can significantly
      improve I-CAD performance.

PMID- 18072499
TI  - A strategy to objectively evaluate the necessity of correcting detected target
      deviations in image guided radiotherapy.
AB  - Image guided radiotherapy technologies are being increasingly utilized in the
      treatment of various cancers. These technologies have enhanced the ability to
      detect temporal and spatial deviations of the target volume relative to planned
      radiation beams. Correcting these detected deviations may, in principle, improve
      the accuracy of dose delivery to the target. However, in many situations, a
      clinical decision has to be made as to whether it is necessary to correct some of
      the deviations since the relevant dosimetric impact may or may not be
      significant, and the corresponding corrective action may be either impractical or
      time consuming. Ideally this decision should be based on objective and
      reproducible criteria rather than subjective judgment. In this study, a strategy
      is proposed for the objective evaluation of the necessity of deviation correction
      during the treatment verification process. At the treatment stage, without any
      alteration from the planned beams, the treatment beams should provide the desired
      dose coverage to the geometric volume identical to the planning target volume
      (PTV). Given this fact, the planned dose distribution and PTV geometry were used
      to compute the dose coverage and PTV enclosure of the clinical target volume
      (CTV) that was detected from imaging during the treatment setup verification. The
      spatial differences between the detected CTV and the planning CTV are essentially
      the target deviations. The extent of the PTV enclosure of the detected CTV as
      well as its dose coverage were used as criteria to evaluate the necessity of
      correcting any of the target deviations. This strategy, in principle, should be
      applicable to any type of target deviations, including both target deformable and
      positional changes and should be independent of how the deviations are detected.
      The proposed strategy was used on two clinical prostate cancer cases. In both
      cases, gold markers were implanted inside the prostate for the purpose of
      treatment setup verification and were used to determine potential target
      deviations. To derive the detected CTV geometry from the planning CTV based on
      the locations of the gold markers, the CTV was approximated with an elastic
      semirigid body model. The derived CTV geometry and shape were confirmed with CBCT
      imaging. The evaluation results and the related mathematical equations and
      computational algorithm are presented. It is concluded that the proposed strategy
      is potentially useful in establishing objective criteria for the necessity of
      correction of the target deviations.

PMID- 18072500
TI  - Stereotactic mammography imaging combined with 3D US imaging for image guided
      breast biopsy.
AB  - Stereotactic X-ray mammography (SM) and ultrasound (US) guidance are both
      commonly used for breast biopsy. While SM provides three-dimensional (3D)
      targeting information and US provides real-time guidance, both have limitations.
      SM is a long and uncomfortable procedure and the US guided procedure is
      inherently two dimensional (2D), requiring a skilled physician for both safety
      and accuracy. The authors developed a 3D US-guided biopsy system to be integrated
      with, and to supplement SM imaging. Their goal is to be able to biopsy a larger
      percentage of suspicious masses using US, by clarifying ambiguous structures with
      SM imaging. Features from SM and US guided biopsy were combined, including breast
      stabilization, a confined needle trajectory, and dual modality imaging. The 3D US
      guided biopsy system uses a 7.5 MHz breast probe and is mounted on an upright SM
      machine for preprocedural imaging. Intraprocedural targeting and guidance was
      achieved with real-time 2D and near real-time 3D US imaging. Postbiopsy 3D US
      imaging allowed for confirmation that the needle was penetrating the target. The
      authors evaluated 3D US-guided biopsy accuracy of their system using test
      phantoms. To use mammographic imaging information, they registered the SM and 3D
      US coordinate systems. The 3D positions of targets identified in the SM images
      were determined with a target localization error (TLE) of 0.49 mm. The z
      component (x-ray tube to image) of the TLE dominated with a TLEz of 0.47 mm. The
      SM system was then registered to 3D US, with a fiducial registration error (FRE)
      and target registration error (TRE) of 0.82 and 0.92 mm, respectively. Analysis
      of the FRE and TRE components showed that these errors were dominated by
      inaccuracies in the z component with a FREz of 0.76 mm and a TREz of 0.85 mm. A
      stereotactic mammography and 3D US guided breast biopsy system should include
      breast compression for stability and safety and dual modality imaging for target
      localization. The system will provide preprocedural x-ray mammography information
      in the form of SM imaging along with real-time US imaging for needle guidance to
      a target. 3D US imaging will also be available for targeting, guidance, and
      biopsy verification immediately postbiopsy.

PMID- 18072501
TI  - Design and evaluation of a variable aperture collimator for conformal
      radiotherapy of small animals using a microCT scanner.
AB  - Treatment of small animals with radiation has in general been limited to planar
      fields shaped with lead blocks, complicating spatial localization of dose and
      treatment of deep-seated targets. In order to advance laboratory radiotherapy
      toward what is accomplished in the clinic, we have constructed a variable
      aperture collimator for use in shaping the beam of microCT scanner. This unit can
      image small animal subjects at high resolution, and is capable of delivering
      therapeutic doses in reasonable exposure times. The proposed collimator consists
      of two stages, each containing six trapezoidal brass blocks that move along a
      frame in a manner similar to a camera iris producing a hexagonal aperture of
      variable size. The two stages are offset by 30 degrees and adjusted for the
      divergence of the x-ray beam so as to produce a dodecagonal profile at isocenter.
      Slotted rotating driving plates are used to apply force to pins in the collimator
      blocks and effect collimator motion. This device has been investigated through
      both simulation and measurement. The collimator aperture size varied from 0 to
      8.5 cm as the driving plate angle increased from 0 to 41 degrees. The torque
      required to adjust the collimator varied from 0.5 to 5 N x m, increasing with
      increasing driving plate angle. The transmission profiles produced by the scanner
      at isocenter exhibited a penumbra of approximately 10% of the collimator aperture
      width. Misalignment between the collimator assembly and the x-ray source could be
      identified on the transmission images and corrected by adjustment of the
      collimator location. This variable aperture collimator technology is therefore a
      feasible and flexible solution for adjustable shaping of radiation beams for use
      in small animal radiotherapy as well as other applications in which beam shaping
      is desired.

PMID- 18072502
TI  - Monte Carlo study of correction factors for the use of plastic phantoms in
      clinical electron dosimetry.
AB  - In some recent dosimetry protocols, plastic is allowed as a phantom material for
      the determination of an absorbed dose to water in electron beams, especially for
      low energy with beam qualities R50 < 4 g/cm2. In electron dosimetry with plastic,
      a depth-scaling factor, cpl, and a chamber-dependent fluence correction factor,
      h(pl), are needed to convert the dose measured at a water-equivalent reference
      depth in plastic to a dose at a reference depth in water. The purpose of this
      study is to calculate correction factors for the use of plastic phantoms for
      clinical electron dosimetry using the EGSnrc Monte Carlo code system. RMI-457 and
      WE-211 were investigated as phantom materials. First the c(pl) values for plastic
      materials were calculated as a function of a half-value depth of maximum
      ionization, I50, in plastic. The c(pl) values for RMI-457 and WE-211 varied from
      0.992 to 1.002 and from 0.971 to 0.979, respectively, in a range of nominal
      energies from 4 MeV to 18 MeV, and varied slightly as a function of I50 in
      plastic. Since h(pl) values depend on the wall correction factor, P(wall), of the
      chamber used, they are evaluated using a pure electron fluence correction factor,
      phi(pl)w, and P(wall)w and P(wall)pl, for a combination of water or plastic
      phantoms and plane-parallel ionization chambers (NACP-02, Markus and Roos). The
      phi(pl)w and P(wall) (P(wall)w and P(wall)pl) values were calculated as a
      function of the water-equivalent depth in plastic materials and at a reference
      depth as a function of R50 in water, respectively. The phi(pl)w values varied
      from 1.024 at 4 MeV to 1.013 at 18 MeV for RMI-457, and from 1.025 to 1.016 for
      WE-211. P(wall)w values for plane-parallel chambers showed values in the order of
      1.5% to 2% larger than unity at 4 MeV, consistent with earlier results. The
      P(wall)pl values of RMI-457 and WE-211 were close to unity for all the energy
      beams. Finally, calculated h(pl) values of RMI-457 ranged from 1.009 to 1.005,
      from 1.010 to 1.003 and from 1.011 to 1.007 for NACP-02, Markus and Roos
      chambers, respectively, in the range of 4 MeV to 18 MeV, and the values of WE-211
      were 1.010 to 1.004, 1.010 to 1.004 and 1.012 to 1.008, respectively. The
      calculated h(pl), values for the Markus chamber agreed within their combined
      uncertainty with the measured data.

PMID- 18072503
TI  - Development of a fully automatic scheme for detection of masses in whole breast
      ultrasound images.
AB  - Ultrasonography has been used for breast cancer screening in Japan. Screening
      using a conventional hand-held probe is operator dependent and thus it is
      possible that some areas of the breast may not be scanned. To overcome such
      problems, a mechanical whole breast ultrasound (US) scanner has been proposed and
      developed for screening purposes. However, another issue is that radiologists
      might tire while interpreting all images in a large-volume screening; this
      increases the likelihood that masses may remain undetected. Therefore, the aim of
      this study is to develop a fully automatic scheme for the detection of masses in
      whole breast US images in order to assist the interpretations of radiologists and
      potentially improve the screening accuracy. The authors database comprised 109
      whole breast US imagoes, which include 36 masses (16 malignant masses, 5
      fibroadenomas, and 15 cysts). A whole breast US image with 84 slice images
      (interval between two slice images: 2 mm) was obtained by the ASU-1004 US scanner
      (ALOKA Co., Ltd., Japan). The feature based on the edge directions in each slice
      and a method for subtracting between the slice images were used for the detection
      of masses in the authors proposed scheme. The Canny edge detector was applied to
      detect edges in US images; these edges were classified as near-vertical edges or
      near-horizontal edges using a morphological method. The positions of mass
      candidates were located using the near-vertical edges as a cue. Then, the located
      positions were segmented by the watershed algorithm and mass candidate regions
      were detected using the segmented regions and the low-density regions extracted
      by the slice subtraction method. For the removal of false positives (FPs), rule
      based schemes and a quadratic discriminant analysis were applied for the
      distribution between masses and FPs. As a result, the sensitivity of the authors
      scheme for the detection of masses was 80.6% (29/36) with 3.8 FPs per whole
      breast image. The authors scheme for a computer-aided detection may be useful in
      improving the screening performance and efficiency.

PMID- 18072504
TI  - Experimental investigation of the response of an amorphous silicon EPID to
      intensity modulated radiotherapy beams.
AB  - The aim of this work was to experimentally determine the difference in response
      of an amorphous silicon (a-Si) electronic portal imaging device (EPID) to the
      open and multileaf collimator (MLC) transmitted beam components of intensity
      modulated radiation therapy (IMRT) beams. EPID dose response curves were measured
      for open and MLC transmitted (MLCtr) 10 x 10 cm2 beams at central axis and with
      off axis distance using a shifting field technique. The EPID signal was obtained
      by replacing the flood-field correction with a pixel sensitivity variation matrix
      correction. This signal, which includes energy-dependent response, was then
      compared to ion-chamber measurements. An EPID calibration method to remove the
      effect of beam energy variations on EPID response was developed for IMRT beams.
      This method uses the component of open and MLCtr fluence to an EPID pixel
      calculated from the MLC delivery file and applies separate radially dependent
      calibration factors for each component. The calibration procedure does not
      correct for scatter differences between ion chamber in water measurements and
      EPID response; these must be accounted for separately with a kernel-based
      approach or similar method. The EPID response at central axis for the open beam
      was found to be 1.28 +/- 0.03 of the response for the MLCtr beam, with the ratio
      increasing to 1.39 at 12.5 cm off axis. The EPID response to MLCtr radiation did
      not change with off-axis distance. Filtering the beam with copper plates to
      reduce the beam energy difference between open and MLCtr beams was investigated;
      however, these were not effective at reducing EPID response differences. The
      change in EPID response for uniform sliding window IMRT beams with MLCtr dose
      components from 0.3% to 69% was predicted to within 2.3% using the separate EPID
      response calibration factors for each dose component. A clinical IMRT image
      calibrated with this method differed by nearly 30% in high MLCtr regions from an
      image calibrated with an open beam calibration factor only. Accounting for the
      difference in EPID response to open and MLCtr radiation should improve IMRT
      dosimetry with a-Si EPIDs.

PMID- 18072505
TI  - Automated volume analysis of head and neck lesions on CT scans using 3D level set
      segmentation.
AB  - The authors have developed a semiautomatic system for segmentation of a diverse
      set of lesions in head and neck CT scans. The system takes as input an
      approximate bounding box, and uses a multistage level set to perform the final
      segmentation. A data set consisting of 69 lesions marked on 33 scans from 23
      patients was used to evaluate the performance of the system. The contours from
      automatic segmentation were compared to both 2D and 3D gold standard contours
      manually drawn by three experienced radiologists. Three performance metric
      measures were used for the comparison. In addition, a radiologist provided
      quality ratings on a 1 to 10 scale for all of the automatic segmentations. For
      this pilot study, the authors observed that the differences between the automatic
      and gold standard contours were larger than the interobserver differences.
      However, the system performed comparably to the radiologists, achieving an
      average area intersection ratio of 85.4% compared to an average of 91.2% between
      two radiologists. The average absolute area error was 21.1% compared to 10.8%,
      and the average 2D distance was 1.38 mm compared to 0.84 mm between the
      radiologists. In addition, the quality rating data showed that, despite the very
      lax assumptions made on the lesion characteristics in designing the system, the
      automatic contours approximated many of the lesions very well.

PMID- 18072506
TI  - Quantification of accuracy of the automated nonlinear image matching and
      anatomical labeling (ANIMAL) nonlinear registration algorithm for 4D CT images of
      lung.
AB  - The performance of the ANIMAL (Automated Nonlinear Image Matching and Anatomical
      Labeling) nonlinear registration algorithm for registration of thoracic 4D CT
      images was investigated. The algorithm was modified to minimize the incidence of
      deformation vector discontinuities that occur during the registration of lung
      images. Registrations were performed between the inhale and exhale phases for
      five patients. The registration accuracy was quantified by the cross-correlation
      of transformed and target images and distance to agreement (DTA) measured based
      on anatomical landmarks and triangulated surfaces constructed from manual
      contours. On average, the vector DTA between transformed and target landmarks was
      1.6 mm. Comparing transformed and target 3D triangulated surfaces derived from
      planning contours, the average target volume (GTV) center-of-mass shift was 2.0
      mm and the 3D DTA was 1.6 mm. An average DTA of 1.8 mm was obtained for all
      planning structures. All DTA metrics were comparable to inter observer
      uncertainties established for landmark identification and manual contouring.

PMID- 18072507
TI  - A short-scan reconstruction for cone-beam CT using shift-invariant FBP and equal
      weighting.
AB  - A 3D reconstruction formula has been derived for a circular cone-beam (CB) short
      scan using ID shift-invariant filtering, CB backprojection, and equal weighting.
      By first converting the divergent projections to parallel projections, we analyze
      the circular CB data using the classic central slice theorem. The sampling
      density in Fourier space is investigated and 1D shift-invariant filtering before
      backprojection can be used to compensate for the nonuniformity. The final formula
      consists of a conventional FDK reconstruction and a correction term using
      differential backprojection and the 1D Hilbert transform in the image domain. On
      a full scan, the approach reduces to the FDK algorithm, while for a short scan,
      the CB artifacts are suppressed by the second term. This algorithm outperforms
      the modified FDK algorithm with Parker's weighting, as illustrated by computer
      simulations and experimental results. Due to its shift-invariant filtered
      backprojection structure, the proposed algorithm is implemented efficiently, and
      requires a simple adaptation of the FDK algorithm.

PMID- 18072508
TI  - Development of a mechanical testing assay for fibrotic murine liver.
AB  - In this article, a novel protocol for mechanical testing, combined with finite
      element modeling, is presented that allows the determination of the elastic
      modulus of normal and fibrotic murine livers and is compared to an independent
      mechanical testing method. The novel protocol employs suspending a portion of
      murine liver tissue in a cylindrical polyacrylamide gel, imaging with a microCT,
      conducting mechanical testing, and concluding with a mechanical property
      determination via a finite element method analysis. More specifically, the finite
      element model is built from the computerized tomography (CT) images, and boundary
      conditions are imposed in order to simulate the mechanical testing conditions.
      The resulting model surface stress is compared to that obtained during mechanical
      testing, which subsequently allows for direct evaluation of the liver modulus.
      The second comparison method involves a mechanical indentation test performed on
      a remaining liver lobe for comparison. In addition, this lobe is used for
      histological analysis to determine relationships between elasticity measurements
      and tissue health. This complete system was used to study 14 fibrotic livers
      displaying advanced fibrosis (injections with irritant), three control livers
      (injections without irritant), and three normal livers (no injections). The
      moduli evaluations for nondiseased livers were estimated as 0.62 +/- 0.09 kPa and
      0.59 +/- 0.1 kPa for indenter and model-gel-tissue (MGT) assay tests,
      respectively. Moduli estimates for diseased liver ranged from 0.6-1.64 kPa and
      0.96-1.88 kPa for indenter and MGT assay tests, respectively. The MGT modulus,
      though not equivalent to the modulus determined by indentation, demonstrates a
      high correlation, thus indicating a relationship between the two testing methods.
      The results also showed a clear difference between nondiseased and diseased
      livers. The developed MGT assay system is quite compact and could easily be
      utilized for controlled evaluation of soft-tissue moduli as shown here. In
      addition, future work will add the correlative method of elastography such that
      direct controlled validation of measurement on tissue can be determined.

PMID- 18072509
TI  - Image-guided high dose rate endorectal brachytherapy.
AB  - Fractionated high dose rate endorectal brachytherapy (HDR-EBT) using CT-based
      treatment planning is an alternative method for preoperative down-sizing and down
      staging of advanced rectal adeno-carcinomas. The authors present an image
      guidance procedure that was developed to ensure daily dose reproducibility for
      the four brachytherapy treatment fractions. Since the applicator might not be
      placed before each treatment fraction inside the rectal lumen in the same manner
      as it was placed during the 3D CT volume acquisition used for treatment planning,
      there is a shift along the catheter axis that may have to be performed. The
      required shift is determined by comparison of a daily radiograph with the
      treatment planning digitally-reconstructed radiograph (DRR). A procedure is
      developed for DRR reconstruction from the 3D data set used for the treatment
      planning, and two possible daily longitudinal shifts are illustrated: above and
      below the planning dose distribution. The authors also describe the procedure for
      rotational alignment illustrated on a clinical case. Reproduction of the
      treatment planned dose distribution on a daily basis is crucial for the success
      of fractionated 3D based brachytherapy treatments. Due to the cylindrical
      symmetry of the applicator used for preoperative HDR-EBT, two types of
      adjustments are necessary: applicator rotation and dwell position shift along the
      applicator's longitudinal axis. The impact of the longitudinal applicator shift
      prior to treatment delivery for 62 patients treated in our institution is also
      assessed.

PMID- 18072510
TI  - Soft-tissue detectability in cone-beam CT: evaluation by 2AFC tests in relation
      to physical performance metrics.
AB  - Soft-tissue detectability in cone-beam computed tomography (CBCT) was evaluated
      via two-alternative forced-choice (2AFC) tests. Investigations included the
      dependence of detectability on radiation dose, the influence of the asymmetric
      three-dimensional (3D) noise-power spectrum (NPS) in axial and sagittal or
      coronal planes, and the effect of prior knowledge on detectability. Custom-built
      phantoms (approximately 15 cm diameter cylinders) containing soft-tissue
      simulating spheres of variable contrast and diameter were imaged on an
      experimental CBCT bench. The proportion of correct responses (Pcorr) in 2AFC
      tests was analyzed as a figure of merit, ideally equal to the area under the
      receiver operating characteristic curve. Pcorr was evaluated as a function of the
      sphere diameter (1.6-12.7 mm), contrast (20-165 HU), dose (1-7 mGy), plane of
      visualization (axial/sagittal), apodization filter (Hanning and Ram-Lak), and
      prior knowledge provided to the observer [ranging from stimulus known exactly
      (SKE) to stimulus unknown (SUK)]. Detectability limits were characterized in
      terms of the dose required to achieve a given level of Pcorr (e.g., 70%). For
      example, a 20 HU stimulus of diameter down to approximately 6 mm was detected
      with Pcorr 70% at dose > or =2 mGy. Detectability tended to be greater in axial
      than in sagittal planes, an effect amplified by sharper apodization filters in a
      manner consistent with 3D NPS asymmetry. Prior knowledge had a marked influence
      on detectability--e.g., Pcorr for a approximately 6 mm (20 HU) sphere was
      approximately 55%-65% under SUK conditions, compared to approximately 70%-85% for
      SKE conditions. Human observer tests suggest practical implications for
      implementation of CBCT: (i) Detectability limits help to define minimum-dose
      imaging techniques for specific imaging tasks; (ii) detectability of a given
      structure can vary between axial and sagittal/coronal planes, owing to the
      spatial-frequency content of the 3D NPS in relation to the imaging task; and
      (iii) performance under SKE conditions (e.g., image guidance tasks in which
      lesion characteristics are known) is maintained at a lower dose than in SUK
      conditions (e.g., diagnostic tasks in which lesion characteristics are unknown).

PMID- 18072511
TI  - A method for synchronizing an external respiratory signal with a list-mode PET
      acquisition.
AB  - A method is proposed to synchronize positron emission tomography (PET) list-mode
      data with an externally recorded respiratory signal in the absence of a master
      clock. When the respiratory signal reaches a user-defined threshold, a trigger
      mark is stored in the list-mode file. After the acquisition, synchronization is
      achieved when the stored trigger marks are superimposed on the respiratory curve
      to form a horizontal line over time at the user-defined threshold.
      Synchronization was possible and unequivocal for ten out of ten clinical studies.
      The list-mode acquisition actually started approximately 40 and 4 s after
      acquisition initiation at the user interface of the Philips Gemini and the GE DLS
      PET-CT systems, respectively.

PMID- 18072512
TI  - Sparseness prior based iterative image reconstruction for retrospectively gated
      cardiac micro-CT.
AB  - Recent advances in murine cardiac studies with three-dimensional (3D) cone beam
      micro-CT used a retrospective gating technique. However, this sampling technique
      results in a limited number of projections with an irregular angular distribution
      due to the temporal resolution requirements and radiation dose restrictions. Both
      angular irregularity and undersampling complicate the reconstruction process,
      since they cause significant streaking artifacts. This work provides an iterative
      reconstruction solution to address this particular challenge. A sparseness prior
      regularized weighted l2 norm optimization is proposed to mitigate streaking
      artifacts based on the fact that most medical images are compressible. Total
      variation is implemented in this work as the regularizer for its simplicity.
      Comparison studies are conducted on a 3D cardiac mouse phantom generated with
      experimental data. After optimization, the method is applied to in vivo cardiac
      micro-CT data.

PMID- 18072513
TI  - Effects of residual target motion for image-tracked spine radiosurgery.
AB  - A quality assurance method was developed to investigate the effects of residual
      target motion for hypofractionated spine radiosurgery. The residual target motion
      (target movement between successive image-guided corrections) was measured on
      line via dual x-ray imagers for patients treated with CyberKnife (Accuray, Inc.,
      Sunnyvale, CA), a robotic linear accelerator with intrafractional image-tracking
      capability. The six degree-of-freedom characteristics of the residual target
      motion were analyzed, the effects of such motion on patient treatment delivery
      were investigated by incorporating the probability distribution of the residual
      motion into the treatment planning dose calculations, and deviations of the doses
      from those originally planned were calculated. Measurements using a programmable
      motion phantom were also carried out and compared with the static treatment plan
      calculations. It was found that the residual target motions were patient specific
      and typically on the order of 2 mm. The measured dose distributions incorporating
      the residual target motion also exhibited 2.0 mm discrepancy at the prescription
      isodose level when compared with the static treatment plan calculations. For
      certain patients, residual errors introduced significant uncertainties (-1 Gy)
      for the dose delivered to the spinal cord, especially at the high dose levels
      covering a small volume of the spinal cord (e.g., 0.1 cc). In such cases,
      stringent cord constraints and frequent monitoring of the target position should
      be implemented.

PMID- 18072514
TI  - A new method for quantitative analysis of mammographic density.
AB  - Women with mammographic percent density >50% have a approximately three-fold
      increased risk of developing breast cancer, potentially making them screening
      candidates for breast MRI scanning. The purpose of this work is to introduce a
      new method to quantify mammographic percent density (MPD), and to compare the
      results with the current standard of care for breast density assessment.
      Craniocaudal (CC) and mediolateral oblique (MLO) mammograms for 104 patients were
      digitized and analyzed using an interactive computer-assisted segmentation
      routine implemented for two purposes: (1) to segment the breast area from
      background and radiographic markers, and (2) to segment dense from fatty portions
      of the breast. Our technique was evaluated by comparing the results to
      qualitative estimates determined by a certified breast radiologist using the BI
      RADS Categorical Assessment (1 (fatty) to 4 (dense) scale). Statistically
      significant correlations (two-tailed, p < 0.01) were observed between calculated
      MPD and BI-RADS for both CC (Spearman rho = 0.67) and MLO views (Spearman rho =
      0.71). For the CC view, statistically significant differences were revealed
      between the mean MPD for each BI-RADS category except between fatty (BI-RADS 1)
      and scattered (BI-RADS 2). Finally, for the MLO views, statistically significant
      differences in the mean MPD between all BI-RADS categories were observed.
      Comparing the CC and MLO views revealed a strong positive correlation (Pearson r
      = 0.8) in calculated MPD. In addition, an evaluation of the reproducibility of
      our segmentation demonstrated the average standard deviation of MPD for a
      subsample of eight patients, measured five times, was 1.9% (range: 0.03%-9.9%).
      Eliminating one misassignment reduced the average standard deviation to 0.75%
      (range: 0.03%-3.16%). Further analysis of approximately 10% of the patient sample
      revealed strong agreement (ICC = 0.80-0.85) in the reliability of MPD estimates
      for both mammographic views. Overall, these results demonstrate the feasibility
      of utilizing our approach for quantitative breast density segmentation, which may
      be useful for detecting small changes in MPD introduced through chemoprevention,
      diet, or other interventions.

PMID- 18072515
TI  - Improvement of the cine-CT based 4D-CT imaging.
AB  - An improved 4D-CT utility has been developed on the GE LightSpeed multislice CT
      (MSCT) and Discovery PET/CT scanners, which have the cine CT scan capability. Two
      new features have been added in this 4D-CT over the commercial Advantage 4D-CT
      from GE. One feature was a new tool for disabling parts of the respiratory signal
      with irregular respiration and improving the accuracy of phase determination for
      the respiratory signal from the Varian real-time positioning and monitoring (RPM)
      system before sorting of the cine CT images into the 4D-CT images. The second
      feature was to allow generation of the maximum-intensity-projection (MIP),
      average (AVG) and minimum-intensity-projection (mip) CT images from the cine CT
      images without a respiratory signal. The implementation enables the assessment of
      tumor motion in treatment planning with the MIP, AVG, and mip CT images on the GE
      MSCT and PET/CT scanners without the RPM and the Advantage 4D-CT with a GE
      Advantage windows workstation. Several clinical examples are included to
      illustrate this new application.

PMID- 18072516
TI  - Radioimmunotherapy with radioactive nanoparticles: first results of dosimetry for
      vascularized and necrosed solid tumors.
AB  - Radioimmunotherapy uses monoclonal antibodies that are still labeled with only
      one radioactive atom. The aim of this paper is to assess, by means of MCNPX
      simulations, the doses delivered around and throughout a solid tumor when the
      radioactive atom linked to each antibody is replaced by a 5 nm diameter
      nanoparticle composed of numerous radionuclides. A new model for a spherical
      vascularized tumor has been developed in which the antibody distributions inside
      the tumor can be uniform or heterogeneous. It is also possible to simulate a
      central necrotic core inside the tumor where the concentration of radiolabeled
      antibodies is assumed to be zero. Dosimetry calculations have been performed for
      the beta-emitting radionuclide (90)Y2O3. Preliminary results show that the
      irregularity of vasculature and the presence of a necrotic core have a noticeable
      influence on the deposited dose profiles. Moreover, with a total activity of 5
      and 34 MBq for tumor radii of 0.5 and 1.0 cm, respectively, viable tumor cells
      can receive doses of up to 50 Gy, even if high nonuniformity of the total
      activity is observed in the tumor. These simulations still require accurate
      information about antibody characteristics and necrosis sizes but clearly confirm
      that the use of monoclonal antibodies conjugated to nanoparticles could lead to a
      considerable enhancement of treatment efficacy against cancer.

PMID- 18072517
TI  - Guiding curve based on the normal breathing as monitored by thermocouple for
      regular breathing.
AB  - Adapting radiation fields to a moving target requires information continuously on
      the location of internal target by detecting it directly or indirectly. The aim
      of this study is to make the breathing regular effectively with minimizing stress
      to the patient. A system for regulating patient's breath consists of a
      respiratory monitoring mask (ReMM), a thermocouple module, a screen, inner
      earphones, and a personal computer. A ReMM with thermocouple was developed
      previously to measure the patient's respiration. A software was written in
      LabView 7.0 (National Instruments, TX), which acquires respiration signal and
      displays its pattern. Two curves are displayed on the screen: One is a curve
      indicating the patient's current breathing pattern; the other is a guiding curve,
      which is iterated with one period of the patient's normal breathing curve. The
      guiding curves were acquired for each volunteer before they breathed with
      guidance. Ten volunteers participated in this study to evaluate this system. A
      cycle of the representative guiding curve was acquired by monitoring each
      volunteer's free breathing with ReMM and was then generated iteratively. The
      regularity was compared between a free breath curve and a guided breath curve by
      measuring standard deviations of amplitudes and periods of two groups of
      breathing. When the breathing was guided, the standard deviation of amplitudes
      and periods on average were reduced from 0.0029 to 0.00139 (arbitrary units) and
      from 0.359 s to 0.202 s, respectively. And the correlation coefficients between
      breathing curves and guiding curves were greater than 0.99 for all volunteers.
      The regularity was improved statistically when the guiding curve was used.

PMID- 18072518
TI  - Improved arterial spin labeling method: applications for measurements of cerebral
      blood flow in human brain at high magnetic field MRI.
AB  - Measurements of cerebral blood flow (CBF) with arterial spin labeling (ASL) MRI
      are challenging primarily due to a poor signal-to-noise (SNR) ratio. Therefore,
      methods that improve SNR and minimize measurement errors can play a significant
      role for better estimations of CBF. The purpose of this work was to develop an
      ASL method for measurements of CBF at high magnetic field strength. In the
      proposed multislice ASL method, using in-plane double inversion for labeling,
      stationary spins are kept at equilibrium to avoid T1 relaxation effects, while
      blood water is labeled using a lower magnetic field gradient. Improvement for CBF
      measurements is demonstrated on subjects and by comparison with other multislice
      ASL MRI methods at 1.5 Tesla. Furthermore, echo-planar imaging (EPI) and Turbo
      FLASH (TFL) at 4 T MRI are compared for mapping CBF in human brain using various
      postlabeling delay times. CBF maps were obtained and analyzed within region-of
      interests encompassing either gray matter or white matter. Elimination of T1
      dependence of stationary spins in conjunction with avoidance of magnetization
      transfer mismatch between labeling and control scans lead to improved CBF
      measurements. Although measurements of CBF in brain tissue are feasible at 4 T
      using either EPI or TFL, TFL reduced contaminations from an intravascular signal
      and susceptibility-related artifacts, providing overall more robust CBF
      measurements than EPI. Therefore, the proposed ASL method in combination with TFL
      should be used for measuring CBF of human brain at 4T.

PMID- 18072519
TI  - A three-dimensional statistical approach to improved image quality for multislice
      helical CT.
AB  - Multislice helical computed tomography scanning offers the advantages of faster
      acquisition and wide organ coverage for routine clinical diagnostic purposes.
      However, image reconstruction is faced with the challenges of three-dimensional
      cone-beam geometry, data completeness issues, and low dosage. Of all available
      reconstruction methods, statistical iterative reconstruction (IR) techniques
      appear particularly promising since they provide the flexibility of accurate
      physical noise modeling and geometric system description. In this paper, we
      present the application of Bayesian iterative algorithms to real 3D multislice
      helical data to demonstrate significant image quality improvement over
      conventional techniques. We also introduce a novel prior distribution designed to
      provide flexibility in its parameters to fine-tune image quality. Specifically,
      enhanced image resolution and lower noise have been achieved, concurrently with
      the reduction of helical cone-beam artifacts, as demonstrated by phantom studies.
      Clinical results also illustrate the capabilities of the algorithm on real
      patient data. Although computational load remains a significant challenge for
      practical development, superior image quality combined with advancements in
      computing technology make IR techniques a legitimate candidate for future
      clinical applications.

PMID- 18072521
TI  - Are the five new nurse career pathways the solution?

PMID- 18072520
TI  - A boundary element approach for image-guided near-infrared absorption and scatter
      estimation.
AB  - Multimodality NIR spectroscopy systems offer the possibility of region-based
      vascular and molecular characterization of tissue in vivo. However,
      computationally efficient 3D image reconstruction algorithms specific to these
      image-guided systems currently do not exist. Image reconstruction is often based
      on finite-element methods (FEMs), which require volume discretization. Here, a
      boundary element method (BEM) is presented using only surface discretization to
      recover the optical properties in an image-guided setting. The reconstruction of
      optical properties using BEM was evaluated in a domain containing a 30 mm
      inclusion embedded in two layer media with different noise levels and initial
      estimates. For 5% noise in measurements, and background starting values for
      reconstruction, the optical properties were recovered to within a mean error of
      6.8%. When compared with FEM for this case, BEM showed a 28% improvement in
      computational time. BEM was also applied to experimental data collected from a
      gelatin phantom with a 25 mm inclusion and could recover the true absorption to
      within 6% of expected values using less time for computation compared with FEM.
      When applied to a patient-specific breast mesh generated using MRI, with a 2 cm
      ductal carcinoma, BEM showed successful recovery of optical properties with less
      than 5% error in absorption and 1% error in scattering, using measurements with
      1% noise. With simpler and faster meshing schemes required for surface grids as
      compared with volume grids, BEM offers a powerful and potentially more feasible
      alternative for high-resolution 3D image-guided NIR spectroscopy.

PMID- 18072522
TI  - Duplication fears cloud the latest essence of care benchmark.

PMID- 18072523
TI  - Under the skin of cosmetic nursing.

PMID- 18072524
TI  - Identifying liver disease in children.

PMID- 18072525
TI  - Helping patients to cope with seasonal affective disorder.

PMID- 18072526
TI  - Bowel care. Part 5--a practical guide to digital rectal examination.

PMID- 18072527
TI  - Understanding Meniere's disease 2: treatment options.
AB  - This is the second part of a two-part unit on Meniere's disease and tinnitus.
      Part 1 explored the incidence, causes, risk factors and diagnosis of Meniere's.
      This part examines the treatments available, including medication, surgery,
      lifestyle changes and psychological support. It also highlights the
      unpredictability of the disease and the difficulties healthcare professionals
      face in trying to understand and treat the condition.

PMID- 18072528
TI  - Extra pulmonary tuberculosis.

PMID- 18072529
TI  - Evaluation of an intermittent six-month regimen in new pulmonary tuberculosis
      patients with diabetes mellitus.
AB  - BACKGROUND: The treatment of tuberculosis (TB) with category I regimen of the
      Revised National Tuberculosis Control Programme (RNTCP) for patients with
      diabetes mellitus (DM) needs evaluation. OBJECTIVE: To assess the cure and
      relapse rates in 3 years, among the new smear-positive TB patients with Type-2 DM
      (DMTB) treated with CAT-I regimen (2E3H3R3Z3/4R3H3) of RNTCP. METHODOLOGY: TB
      suspects attending the diabetology units and the TB research centre (TRC)
      Chennai, were investigated. Eligible DMTB cases were enrolled. Baseline
      estimation of cardiac, renal, liver function tests and glycosylated-HBA1c were
      undertaken. All patients received 2E3H3R3Z3/4R3H3 under supervision at TRC.
      Clinical and sputum (smear and culture) examinations and monitoring of diabetic
      status were undertaken every month up to 24 months, then once in 3 months up to
      36 months. RESULTS: Of 100 patients admitted, 7 were excluded for various reasons
      from analysis. Of 93 patients, 87 (94%) had a favourable response at the end of
      treatment. Pre and post treatment mean glycosylated-HBA1c were 9.7% and 8.4% (>7%
      poor control). During follow-up period, 6 died and one lost to follow-up. Of the
      remaining, four relapsed. CONCLUSION: Category-I regimen, recommended for all the
      new smear-positive patients in the Indian TB programme, is effective in the
      treatment of DMTB patients, despite poor control of diabetes.

PMID- 18072531
TI  - Simple direct drug susceptibility tests on sputum samples for early detection of
      resistance in tubercle bacilli.
AB  - BACKGROUND: Direct sensitivity test either by sputum concentrate (DS) or swab
      method (DSM) set up along with the primary culture would avoid the delay of four
      or more weeks required for the indirect test. A comparison of these two methods
      against the standard indirect sensitivity method under routine laboratory
      conditions is necessary to prove their merit. METHOD: Smear positive sputum
      samples were aliquoted and sensitivity tests were set up by both the direct
      methods as also an indirect test set up from the primary culture of the same
      sample. RESULTS: The agreement with the indirect test results for isoniazid (INH)
      ranged from 97-98% for the DS method and 93-97% for the DSM method. The
      corresponding figures were 96-98% by the DS and 94-99% by the DSM method for
      rifampicin (R). The agreement was less satisfactory for ethambutol (Emb).
      CONCLUSION: This study showed that direct sensitivity tests such as DS and DSM
      methods can detect most of the cultures resistant to INH and R (MDR) from the
      time growth appears on the primary culture, even as early as the second week of
      setting up the tests.

PMID- 18072530
TI  - Annual risk of tuberculous infection in Andhra Pradesh, India.
AB  - BACKGROUND: There is paucity of information on epidemiological situation of
      Tuberculosis (TB) in Andhra Pradesh. The DOTS strategy under the Revised National
      Tuberculosis Control Programme (RNTCP) was introduced in the year 2000 to cover
      the entire State by 2005. OBJECTIVES: To estimate the prevalence of tuberculous
      infection among children 5-9 years of age and to compute the average Annual Risk
      of Tuberculosis Infection (ARTI) from the estimated prevalence. METHODS: A
      cluster-sample house-based tuberculin survey was carried out in a representative
      sample of children between 5-9 years of age. The clusters were selected by a two
      stage sampling procedure. At first stage, five districts were selected by
      probability proportional to population size (PPS) method. Depending upon child
      population ratio, 32 clusters allocated to each district were further sub-divided
      into rural and urban clusters selected by simple random sampling. A total of 3636
      children, irrespective of their BCG scar status, were tuberculin tested using one
      TU PPD RT23 with Tween 80 and the maximum transverse diameter of induration was
      measured about 72 hours later. RESULTS: The prevalence of infection estimated by
      mirror-image technique using observed mode of reactions attributable to infection
      with tubercle bacilli at 20mm was 9.6% (95% CI: 8.0-11.2). The ARTI was computed
      at 1.4% (95% CI: 1.1-1.6). CONCLUSION: Survey findings indicate a fairly high
      rate of transmission of tubercle bacilli.

PMID- 18072532
TI  - Status report on RNTCP.

PMID- 18072533
TI  - Tuberculosis presenting as osteolytic soft tissue swellings of skull in HIV
      positive patient: a case report.
AB  - We present a clinical case report of a 40-year old HIV positive male patient
      presenting with fever, cough with expectoration and osteolytic, cystic, multiple
      soft tissue swellings of skull (aspirate showing AFB). The various clinical
      possibilities are discussed along with interpretation of subsequent
      investigations.

PMID- 18072534
TI  - Tuberculous brain abscess in a patient with HIV infection.
AB  - Tuberculous Brain Abscess (TBA) is a rare manifestation of CNS tuberculosis. Only
      a few cases have been reported in literature. A twenty six year old male
      presented with high grade fever, throbbing headache and altered sensorium.
      Examination revealed neck stiffness and papilloedema. His chest X-ray showed
      evidence of healed pulmonary tuberculosis. MRI Brain showed a well circumscribed
      hyper intense lesion in the left parietal region with perilesional edema and mass
      effects. Stereotactic aspiration of the abscess yielded frank creamy pus. PCR for
      Mycobacterium tuberculosis MPB 64 was positive which confirmed the lesion to be
      of tuberculous etiology. Patient responded well to four-drug regimen of
      antitubercular treatment.

PMID- 18072535
TI  - Status of smear-positive TB patients at 2-3 years after initiation of treatment
      under a DOTS programme.
AB  - OBJECTIVE: To describe the status of cases 2-3 years after the initiation of
      treatment under DOTS. SETTING: After DOTS implementation in Tiruvallur district,
      south India, we followed up a cohort of smear-positive TB patients registered
      during 2002-03 after initiation of treatment. RESULTS: The overall mortality rate
      was 15.0% and among the remaining 18.6% had active disease. In multivariate
      analysis, a higher mortality rate was independently associated with age, sex,
      occupation, treatment outcome and initial body weight of patients. CONCLUSION:
      The mortality and morbidity rates are still high during follow-up and needs to be
      curtailed by addressing these issues effectively in TB control programme.

PMID- 18072536
TI  - Pathophysiology and genetics of obesity.
AB  - Obesity, a global problem, is a multifactorial disorder. The factors are
      environmental, metabolic and genetic and their interaction with each other
      regulates the body weight. Imbalance in either of the factors may be responsible
      for weight gain. With advancement of research techniques in the last decade,
      genetic studies have been undertaken for several different causative mutations
      involving obesity loci on different chromosomes. Monogenic and polygenic obesity
      has been observed however, polygenic forms are more common. So far more than 200
      genes in mouse and more than 100 genes in humans have been identified which
      result in phenotypes that affect body weight regulation. In spite of this
      knowledge, the field of obesity has still not been explored extensively. There
      remain a lot of lacuna regarding causes and treatment of obesity. Challenges are
      still there to identify the exact cause of weight gain and the use of current
      knowledge for development of anti-obesity drugs targeted for body weight
      regulation. In this review, we have explained neuropathophysiologic regulation of
      feeding behaviour and some aspects of obesity-genetics especially with single
      nucleotide polymorphism of selected candidate genes and their functional aspects
      mainly in monogenic obesity.

PMID- 18072537
TI  - Cloning of medicinal plants through tissue culture--a review.
AB  - In order to have standardized formulations, the chemical constituents from plants
      and their parts are required to be uniform both qualitatively and quantitatively.
      Furthermore, an ever increasing demand of uniform medicinal plants based
      medicines warrants their mass cloning through plant tissue culture strategy. A
      good number of medicinal plants have been reported to regenerate in vitro from
      their various parts, but a critical evaluation of such reports reveals that only
      a few complete medicinal plants have been regenerated and still fewer have
      actually been grown in soil, while their micropropagation on a mass scale has
      rarely been achieved, particularly in those medicinal plants where conventional
      propagation is inadequate, like, the mass clonal propagation of Dioscorea
      floribunda leading to its successful field trials. Such facts make it imperative
      to document the factual position of micropropagation of medicinal plants bringing
      out the advancements made along with the short falls, in this important area. The
      present review deals with the futuristic view on the said subject restricted to
      higher plants.

PMID- 18072538
TI  - Aprotinin reverses ECG abnormalities induced by Mesobuthus tamulus concanesis,
      Pocock venom in adult rats.
AB  - The kinins are implicated in the pathogenesis of scorpion envenomation.
      Therefore, this study was carried out to examine the involvement of kinins for
      the ECG abnormalities induced by M. tamulus concanesis, (BT) venom in
      anaesthetized rats. ECG was recorded using needle electrodes with limb lead II
      configuration. The PR interval, QRS wave pattern, QRS duration, ST segment and
      heart rate were examined in saline only, venom alone, and venom after aprotinin
      groups. BT venom (5 mg/kg) produced heart block of varying degree and ischemia
      like changes in ECG wave pattern and the animals died within 30 min after
      exposure to venom. In aprotinin pretreated animals, the initial ECG changes
      produced by venom persisted, but after 15 min the ECG pattern improved and the
      animals survived for the entire period of observation (120 min). The results
      indicate that aprotinin protected the rats against the cardiotoxicity induced by
      BT venom.

PMID- 18072539
TI  - Neuroprotective effects of zinc on antioxidant defense system in lithium treated
      rat brain.
AB  - With a view to find out whether zinc affords protection against lithium toxicity
      the activities of antioxidant enzymes and lipid peroxidation profile were
      determined in the cerebrum and cerebellum of lithium treated female Sprague
      Dawley rats. Lipid peroxidation was significantly increased in both the cerebrum
      and the cerebellum of animals administered with lithium for a total duration of 4
      months as compared to the normal control group. On the contrary, the activities
      of catalase and glutathione-s-transferase (GST) were significantly reduced after
      4 months of lithium treatment. The activity of superoxide dismutase (SOD) was
      significantly increased in the cerebrum after 4 months lithium administration,
      whereas in the cerebellum the enzyme activity was unaffected. No significant
      change in the levels of reduced glutathione (GSH) was found in either cerebrum or
      cerebellum after 2 months of lithium treatment. However, 4 months lithium
      treatment did produce significant changes in GSH levels in the cerebrum and in
      the cerebellum. Zinc supplementation for 4 months in lithium-treated rats
      significantly increased the activities of catalase and GST in the cerebellum,
      showing that the treatment with zinc reversed the lithium induced depression in
      these enzyme activities. Though, zinc treatment tended to normalize the SOD
      activity in the cerebrum yet it was still significantly higher in comparison to
      normal levels. From the present study, it can be concluded that the
      antiperoxidative property of zinc is effective in reversing the oxidative stress
      induced by lithium toxicity in the rat brain.

PMID- 18072540
TI  - Free radical induced damages to rat liver subcellular organelles: inhibition by
      Andrographis paniculata extract.
AB  - Aqueous extract of Andrographis paniculata was examined for antioxidant activity
      using rat liver subcellular organelles as model systems. The study deals with two
      important biological oxidative agents, ascorbate-Fe(+2) and AAPH generating
      hydroxyl and peroxyl radical, respectively. Oxidative damage was examined against
      the inhibition of membrane peroxidation, protein oxidation and restoration in
      decreased SOD and catalase activity. The antimutagenic activity of Ap was
      examined following inhibition in AAPH induced strand breaks in plasmid pBR322
      DNA. Extract was a potent scavenger of DPPH, ABTS radicals, exemplified by ESR
      signals, O2-*, *OH and H2O2, displayed excellent reducing power, FRAP potentials
      to reduce Fe (III) --> Fe (II) and had considerable amount of phenolics/
      flavonoids contents, an effective antioxidant index. The observed antioxidant
      effect might be primarily due to its high scavenging ability for ROS. Effect was
      confirmed ex vivo following inhibition in peroxidation, restoration in SOD
      enzyme, SOD band intensity and protein degradation in Ap fed liver homogenate.
      Based on these results, it was concluded that the aqueous extract of Andrographis
      paniculata might emerge as a potent antiradical agent against various
      pathophysiological oxidants.

PMID- 18072541
TI  - Scavenging effect of Indian grape polyphenols on 2,2'-diphenyl-1
      picrylhydrazyl(DPPH) radical by electron spin resonance spectrometry.
AB  - Antioxidant potency of Indian grape cultivars varying in their skin color, seed
      and polyphenol content (Bangalore blue, Pandhari sahebi, Sharad seedless and
      Thompson seedless) and their components (whole grapes, pulp with skin and seeds)
      was examined as 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity
      using electron spin resonance spectrometry. The total polyphenols in Indian
      grapes ranged between 3-51%. Extracted polyphenols caused a concentration
      dependent and significant loss in DPPH radical signal, similar to known
      antioxidants-Vitamin C, catechin and procyanidin B3 used as references. Among
      seedless cultivars, polyphenols from Sharad was more potent as antioxidant than
      Thompson, showing IC50 values of 1250 +/- 30 and 2650 +/- 125 microg/ml,
      respectively. The inhibitory effect of polyphenols from seedless grape cultivars
      was as effective as that of seeded variety. The results indicate that polyphenols
      extracted from Indian grapes/ components (with /without seeds) exhibited free
      radical scavenging activity and their chemopreventive properties need to be
      exploited by in vivo model system.

PMID- 18072542
TI  - Anti-stress and anti-oxidant effects of roots of Chlorophytum borivilianum (Santa
      Pau & Fernandes).
AB  - The aqueous extract of C. borivilianum (250 mg/kg for 7 days) significantly
      reverted the elevated levels of plasma glucose, triglycerides, cholesterol and
      serum corticosterone and also reduced the ulcer index, adrenal gland weight more
      as effectively as the standard drug (diazepam) in rats. At 125 mg/kg po, it
      showed a mild anti-stress activity. Under in vitro 1,1-diphenyl-2-picrylhydrazyl
      (DPPH*) free radical scavenging assay and lipid peroxidation assay the extract
      considerably inhibited, in a dose-dependent manner, the levels of DPPH* free
      radicals and thiobarbituric acid reactive substances, respectively thus showing
      significant antioxidant property. The results suggested that it could be used for
      the treatment of oxidative stress-induced disorders.

PMID- 18072543
TI  - Antioxidant modulation in response to heavy metal induced oxidative stress in
      Cladophora glomerata.
AB  - The present investigation was carried out to study the induction of oxidative
      stress subjected to heavy metal environment. Lipoperoxides showed positive
      correlation at heavy metal accumulation sites indicating the tissue damage
      resulting from the reactive oxygen species and resulted in unbalance to cellular
      redox status. The high activities of ascorbate peroxidase and superoxide
      dismutase probably counter balance this oxidative stress. Glutathione and soluble
      phenols decreased, whereas dehydroascorbate content increased in the algae from
      polluted sites. The results suggested that alga responded to heavy metals
      effectively by antioxidant compounds and scavenging enzymes.

PMID- 18072544
TI  - Alpha1 and alpha2 adrenoceptor mediated melanosome aggregatory responses in vitro
      in Oreochromis mossambica (Peters) melanophores.
AB  - Effects of specific and non-specific adrenoceptor agonists and antagonists were
      examined on the isolated scale melanophores of O. mossambica in physiological
      Ringer solution. The responses were recorded as melanophore size index. It was
      observed that adrenaline, nor-adrenaline, phenylpropanolamine, clonidine and
      phenylepherine induced melanosome aggregation in a dose-dependent manner.
      Denervation of the fish melanophores increased the sensitivity of the
      melanophores to adrenaline but not to nor-adrenaline. Phentolamine (3.55 x 10(-5)
      M), prazosin (2.38 x 10(-5) M) and yohimbine (2.821 x 10(-5) M) significantly
      inhibited the aggregatory responses of the fish melanophores to adrenaline, nor
      adrenaline, clonidine and phenylepherine. The blocking effect of yohimbine was
      significantly higher than that of prazosin. It is concluded that the effect of
      adrenaline is directly mediated through the receptors and alpha2 adrenoceptors
      are predominantly involved in the aggregatory responses of this fish
      melanophores, while alpha1 adrenoceptors presence has been indicated.

PMID- 18072545
TI  - A non-invasive technique for rapid extraction of DNA from fish scales.
AB  - DNA markers are being increasingly used in studies related to population genetics
      and conservation biology of endangered species. DNA isolation for such studies
      requires a source of biological material that is easy to collect, non-bulky and
      reliable. Further, the sampling strategies based on non-invasive procedures are
      desirable, especially for the endangered fish species. In view of above, a rapid
      DNA extraction method from fish scales has been developed with the use of a
      modified lysis buffer that require about 2 hr duration. This methodology is non
      invasive, less expensive and reproducible with high efficiency of DNA recovery.
      The DNA extracted by this technique, have been found suitable for performing
      restriction enzyme digestion and PCR amplification. Therefore, the present DNA
      extraction procedure can be used as an alternative technique in population
      genetic studies pertaining to endangered fish species. The technique was also
      found equally effective for DNA isolation from fresh, dried and ethanol preserved
      scales.

PMID- 18072546
TI  - Purification of elastase-like chymotrypsin from cardamom shoot and Capsule borer
      [corrected].
AB  - An elastase-like chymotrypsin was purified by aprotinin-agarose affinity
      chromatography from the midgut extract of cardamom shoot and capsule borer,
      Conogethes punctiferalis. The purified enzyme had a Vmax of 687.6 +/- 22.1 nmole
      pNA released/min/mg protein, Km of 0.168 +/- 0.012 mM with SAAPLpNA as substrate
      and gave a single band on SDS-PAGE with a molecular mass of 72.1 kDa. Casein
      zymogram revealed one clear zone of proteolytic activity, which corresponded to
      the band obtained with SDS-PAGE indicating that this could be a single
      polypeptide enzyme.

PMID- 18072547
TI  - Angiotensin converting enzyme from sheep mammary, lingual and other tissues.
AB  - Occurrence of angiotensin converting enzyme (ACE) in mammary gland and tongue
      taste epithelium was demonstrated for the first time. Six times higher ACE
      activity in lactating mammary gland, than non-lactating mammary gland, suggested
      pregnancy and lactation hormonal dependent expression of ACE in female mammals.
      ACE activity was highest in choroid plexus, less in spinal cord and moderate in
      cerebrum, medulla, cerebellum and pons. Distribution of ACE in different regions
      of skin, kidney and among other tissues was different. Presence of ACE in adrenal
      glands, pancreas, bone marrow and thyroid gland indicated functions other than
      blood pressure homeostasis for this enzyme.

PMID- 18072548
TI  - [Ultrasonic techniques for removing broken instruments from root canal].
AB  - Instruments broken in root canal is one of the frequent complications of
      endodontic therapy and fortunately, as the rapid development of microscope using
      in the root canal treatment, most of the broken instruments can be removed with
      the assistance of ultrasonic appliances. In the present study, we talked about
      the causes, the removing methods of broken instruments and troubles during the
      procedures. We put much emphasis on the creation of a straight pathway along the
      canal as well as some concerns in using the ultrasonic appliances, such as the
      water spray, the rotating actions and the assistance of microscope, all of which
      are supposed to offer great benefits for clinically avoiding as well as dealing
      with broken instruments.

PMID- 18072549
TI  - [Early effects of the cyclic uniaxial compressive stress on Actin and Vimentin of
      the rat condylar chondrocytes].
AB  - OBJECTIVE: To investigate the early effects of the cyclic uniaxial compressive
      stress on Actin and Vimentin of the rat condylar chondrocyte. METHODS: The third
      passage chondrocyte were harvested from the mandibular condyles of 2-day-old
      rats, and a cellular compressive stress device was used to apply stress on cells
      at 4 000 microstrain for 15, 30, 60, 120, 240 min. The early effects of the
      cyclic uniaxial compressive stress on Actin and Vimentin of the rat mandibular
      condylar chondrocytes were examined by laser scanning confocal microscope (LSCM),
      immunofluorescence technique and Western blot. RESULTS: The expression of
      fluorescent light of cys-toskeleton protein changed obviously with 4000
      microstrain compressive stress loading. The expression of Actin significantly
      decreased in 60 min, and the expression of Vimentin decreased in 30 min. Then the
      expression of these two protein recovered in 120 min. CONCLUSION: There are time
      responsiveness between the 4000 microstrain compressive stress stimulate and
      Actin, Vimentin. It shows the expression of Actin and Vimentin down-regulated at
      first under the compressive stress, then increased by feedback. It hints that
      there are "self-regulate" mechanisms in the cell response to mechanics stimulate.

PMID- 18072550
TI  - [Wear behavior of enamel and veneering ceramics].
AB  - OBJECTIVE: To compare the wear between the enamel and two types of dental
      decoration porcelains for all-ceramic restorations (Vita-alpha, Vintage AL).
      METHODS: Friction coefficients, wear scar width, element concentrations and wear
      surface evolution were considered relatively to the tribology of that in vivo
      situation. The wear scars of the samples were characterized by means of dynamic
      atomic force microscopy (DFM). The different element concentrations of the
      surface before/after the wear test were determined with energy dispersion
      spectrometry (EDS). RESULTS: The friction coefficient varied from time in each
      kind of material. The statistical differences between materials were observed in
      wear scar width and properties of materials (P<0.05). DFM results showed wear
      surface of natural tooth full of abrasive particles and denaturation of dental
      texture. Wear surface of veneering ceramics consisted mainly of abrasive
      particles, plough and microcracking. EDS results showed that the element
      concentration of Fe was obviously found on the samples after wear. CONCLUSION:
      The main underlying mechanisms of natural teeth wear are abrasive, and
      denaturation of dental texture. Abrasive wear, adhesion and fatigue of veneering
      ceramics characterize the wear patterns which plays different role in Vita-alpha
      and Vintage AL. The wear patterns of veneering ceramics can be described as mild
      wear.

PMID- 18072552
TI  - [Effect of astragalus polysaccharides on the proliferation and ultrastructure of
      dog bone marrow stem cells induced into osteoblasts in vitro].
AB  - OBJECTIVE: To observe the growth and osteogenic property of cultured dog bone
      marrow stem cells (BMSCs) by investigating the effects of astragalus
      polysaccharides (APS) on the proliferation and ultrastructure of BMSCs into
      osteoblasts in vitro. METHODS: BMSCs osteogenic property was detected by improved
      Wright-Giemsa, Gomori and alizarin dyeing method. The proliferation and
      differentiation of the induced BMSCs with APS in different concentration and time
      were detected by MTT assay and the morphologic change of the induced BMSCs was
      observed by transmission electron microscope (TEM). RESULTS: BMSCs osteogenic
      property was detected with Wright-Giemsa deep-bluing, Gomori method blacking and
      with more mineral nodules alizarin dyeing method carmining. APS with
      concentration of 0.005 mg/mL can promote the proliferation of the induced BMSCs
      in short-term culture (1th, 3th day) and 50 mg/mL can decrease the effect through
      long-term culture (5th day). Observed by TEM (5th day), the number of
      mitochondria, rough endoplasmic reticulum increased and the extracellular matrix
      was excreted more in the induced BMSCs by APS with concentration of 0.005 mg/mL.
      However, not only the number of mitochondria, rough endoplasmic reticulum reduced
      but also the structure was swollen, degenerative, membrance damaged in the
      induced BMSCs by APS with concentration of 50 mg/mL. CONCLUSION: APS with lower
      concentration in short-term culture may promote BMSCs proliferation and
      differentiation.

PMID- 18072551
TI  - [Histopathology research of Cinnamaldehyde as pulp-cap of pulpotomy in rats].
AB  - OBJECTIVE: To investigate the stimulation of Cinnamaldehyde to the pulp tissue
      and the periapical tissue of rats' teeth, to provide evidence for developing
      Cinnamaldehyde as a pulp-cap of pulpotomy in primary teeth. METHODS: Using
      Cinnamaldehyde as pulp-cap in pulpotomy of rats' teeth, set up Cinnamaldehyde
      group, formaldehyde cresol formocresol group and blank group. After different
      treatment according to the empirical procedure, rats were killed in the 4th week
      and on the 12th week. Then the experiment teeth and the periodontal tissue were
      made into HE slides and observed using light microscope. RESULTS: The 4" week,
      internal absorption, external absorption, and calcification were of no
      significance among all the groups. Inflammation in blank group was far more
      severe than that in other two groups (P<0.05), while the latter two were of no
      significance. The 12th week, internal absorption, external absorption, and
      inflammation between the former two groups were of no differences, but the
      indexes were significantly different from them of the blank group (P<0.005).
      Calcify was not obvious in all the slides. CONCLUSION: As a pulp-cap,
      Cinnamaldehyde stimulates the pulp tissue and the periapical tissue at a very low
      level. The research provides histopathology rationale for Cinnamaldehyde as pulp
      cap of pulpotomy in primary teeth.

PMID- 18072553
TI  - [Effects of simulating static magnetic fields of magnetic attachments on
      osteoblasts proliferation, cell cycle distribution and apoptosis ratio].
AB  - OBJECTIVE: To investigate the effects of the static magnetic field (SMF)
      generated by dental magnetic attachments on osteoblastic proliferations, cell
      cycle distribution, and apoptosis ratio. METHODS: By simulating those of the
      closed-field, the closure process and the open-field Magnedisc 800 magnetic
      attachments respectively, the in vitro cultured rat osteoblasts were exposed
      continuously to 12.5, 125, 250 mT SMF. The effects of the SMF on the
      proliferation of the cells were examined. MTT colorimetry test was performed to
      detect the effect of the SMF on the vitalities of cells. Flow cytometry was
      utilized to analyze the cell cycles and cell apoptosis rates. RESULTS: The SMF
      exposure didn't change the vital osteoblasts number, the cell cycle distribution
      and proliferation activities of osteoblasts. The cell apoptosis situation were
      not observed statistical differences. CONCLUSION: No matter the closed-field, the
      closure process and the open-field magnetic attachments respectively, continuous
      simulating SMF-stimulation of magnetic attachments couldn't change osteoblasts
      proliferation activity, cell cycle distribution, and apoptosis ratio.

PMID- 18072554
TI  - [Influence of thermochemotherapy on the activity of cytotoxic T lymphocyte in
      oral maxillofacial cancer patients].
AB  - OBJECTIVE: To study the influence of thermochemotherapy on the activity of
      cytotoxic T lymphocyte (CTL) in peripheral blood of patients with oral
      maxillofacial cancer. METHODS: Twenty-one subjects with oral maxillofacial cancer
      were treated by thermochemotherapy, and the activity of CTL in peripheral blood
      was analyzed. RESULTS: Thermochemotherapy can obviously enhance the activity of
      CTL (P<0.01). CONCLUSION: Thermochemotherapy can enhance the activity of CTL,
      thus enhance the patient's immune function. Therefore, it can enhance the
      antitumor response in whole body.

PMID- 18072555
TI  - [Expression of CIC-5 in rat tooth germ development].
AB  - OBJECTIVE: To determine the expression and possible function of CIC-5 during the
      rat tooth germ development. METHODS: Isolated total mRNA and protein from the rat
      tooth germs which were at different stages of development. RT-PCR and Western
      blot were used to investigate the mRNA and protein expression of the CIC-5 in the
      rat tooth germ. RESULTS: The mRNA and protein of CIC-5 expressed in the late bell
      stage, but undetected inThe mRNA and protein of CIC-5 expressed in the late bell
      stage, but undetected in the early or middle bell stage. CONCLUSION: These
      results showed the spatial temporal distribution of expression of CIC-5 during
      the different stages of the rat tooth germ development and suggested that it
      might contribute to the rat tooth germ development.

PMID- 18072556
TI  - [Application of all-ceramic laminates veneer with Vita VM9 in clinic].
AB  - OBJECTIVE: To evaluate the effects of all-ceramic veneers in clinic fabricated by
      computer aided design/computer aided manufacturing (CAD/CAM) system and veneered
      with Vita VM9. METHODS: 54 all-ceramic veneers were made for 12 patients. The
      patients were divided into three groups: Tetracycline staining group, fluorosis
      group and devitalization group. The color of patients' teeth was checked before
      and after laminates with Shade Eye. All-ceramic veneers was checked on the white
      background and abutment background. The value of L*, a* and b* were calculated to
      compare the color difference among 3 groups. The color, fitness and fracture of
      all-ceramic veneers were checked in clinic after restoration every 3 months.
      RESULTS: All-ceramic veneers as a replacement for discolored teeth showed good
      appearance. The substructures and veneers showed significant color difference
      between white background and abutment background in tetracycline staining group
      and devitalization group, but there was no significant color difference in
      fluorosis group. All veneers had good esthetic effect, excellent marginal fit,
      good gingival and adjacent condition. The fracture was not found in clinic.
      CONCLUSION: The effects of all-ceramic veneers were perfect in color, fitness and
      stability to fracture. Fluorosis teeth is the best indication for all-ceramic
      veneers. To tetracycline teeth and devital teeth, the fundic porcelain with deep
      color should be chosen, or an opaquing material be applied as fundus in all
      ceramic veneers repairing.

PMID- 18072557
TI  - [Influence of different types of posts and cores on color of IPS-Empress 2
      crown].
AB  - OBJECTIVE: To evaluate the influence of different types of posts and cores on the
      final color of the IPS-Emperss 2 crown. METHODS: Five types of posts and cores
      (Cerapost with Empress cosmo, Cerapost with composite resin, gilded Ni-Cr alloy,
      gold alloy and Ni-Cr alloy) were made. The shifts in color of three points of IPS
      Empress 2 crown surface (cervical, middle and incisal) with different posts and
      cores was measured with a spectroradiometer (PR-650). RESULTS: The L* a* b*
      values of zirconium oxide and gilded Ni-Cr alloy posts and cores with ceramic
      crown were the highest. The L* a* values of zirconium oxide posts composite cores
      were higher while the b* values were lower. The L* a* b* values of Ni-Cr alloy
      were lower than that of gold alloy and were the lowest. CONCLUSION: In
      combination with IPS-Empress 2 crown, zirconium oxide posts are suitable for
      routine use in the anterior dentition, and gilded Ni-Cr alloy and gold alloy
      posts and cores can be recommended for clinical practice. Ni-Cr alloy posts and
      cores can not be recommended for clinical practice.

PMID- 18072558
TI  - [Quantification of Tannerella forsythensis in chronic periodontitis patients].
AB  - OBJECTIVE: To compare the number of the Tannerella forsythensis (T.
      forsythensis), total bacteria, and proportion of T. forsythensis in subgingival
      specimens in diseased sites of chronic periodontitis patients and in healthy
      sites of periodontally healthy subjects, and clarify the relationship between
      bacterial load and periodontal status. METHODS: Subgingival plaque samples from
      61 chronic periodontitis patients and 12 healthy controls (positive for T.
      forsythensis by conventional PCR) were analyzed with TaqMan real-time polymerase
      chain reaction assay for T. forsythensis and total bacteria. Quantification was
      performed with species-specific primer/probe, universal primer/ probe and serial
      dilution of plasmid standards. RESULTS: Numbers of T. forsythensis and total
      bacteria(P<0.001) , the proportion of T. forsythensis in subgingival specimens
      (P<0.05) were significant higher in diseased sites of chronic periodontitis
      patients than in healthy sites of healthy subjects. In addition, a significant
      correlation was found between the number of bacteria and various probing depth
      (P<0.001). There was no significantly difference between the proportion of T.
      forsythensis in subgingival plaque and probing depth. CONCLUSION: Number of T.
      forsythensis are closely associated with periodontal status, and demonstrate the
      broad potential of real-time polymerase chain reaction application on
      periodontology.

PMID- 18072559
TI  - [Early treatment of middle ear disease in cleft palate infants].
AB  - OBJECTIVE: To explore the effect of myringotomy with insertion of tube and
      tympanocentesis on alleviating secretory otitis media (SOM) and hearing loss in
      cleft palate infants. METHODS: Nineteen cleft lip and palate infants with SOM and
      hearing loss (38 ears) were treated with myringotomy with insertion of
      ventilation tube at the same time of repair of the cleft lip, who were performed
      averagely at 6.9 months of age. Fifteen cleft lip and palate infants with SOM (30
      ears) were treated with tympanocentesis at the same time of repair of the cleft
      lip averagely at 6.6 months of age. All cases were followed up from 1 week to 12
      months and estimated by auditory brainstem response (ABR) and acoustic immitance
      audiometry. RESULTS: The average wave V reacting thresholds of ABR were
      separately 55.41 dBnHL and 28.48 dBnHL, and 79.17% tympanogram B changed to
      tympanogram A in cleft palate infants with insertion of tube before and after
      operation. The average wave V reacting thresholds of ABR were separately 40.63
      dBnHL and 26.50 dBnHL, and 40.91% tympanogram B changed to tympanogram A in cleft
      palate infants with tympanocentesis preoperatively and in 1 week postoperatively,
      in whom the average hearing thresholds and tympanograms had no significant
      difference preoperatively and in 1 or 3 months postoperatively (P>0.05).
      CONCLUSION: The early myringotomy with insertion of tube is effective to restore
      the function of the middle ear in cleft palate infants with SOM, so to suggest to
      be performed at the same time of the repair of cleft lip within the first 1-year
      of life. The tympanocentesis should not be used as a regular management in the
      cleft palate infants with SOM.

PMID- 18072560
TI  - [Effects of non-surgical treatment on temporomandibular joint of adult low-angle
      subjects with severe skeletal class III deformity].
AB  - OBJECTIVE: To investigate effects of non-surgical treatment on temporal
      mandibular joint(TMJ) of adult low-angle subjects with severe skeletal Class III
      deformity. METHODS: Thirteen low-angle patients with severe skeletal Class III
      malocclusion (male 5, female 8) were included in the study. The average age was
      21.3 years old. They were treated with OPA-K straight wire technique. Helkimo
      index evaluation was made before and after treatment. Lateral cephalometric films
      and corrected TMJ lateral cephalometric radiograghs were taken before and after
      treatment, and linear and area measurement were observed. All data were analyzed
      with SPSS 12.0 software. RESULTS: After non-surgical treatment, Helkimo indexes
      of all patients redistributed. The line distance and area of anterior space in
      TMJ increased while the posterior space decreased. Linear percent decreased from
      20.81% to 8.04%, and area proportion decreased from 1.62 to 1.01. Anterior space
      was the same as the posterior. Condyles and mandibles were retruded. CONCLUSION:
      After non-surgical therapy in adult low-angle subjects with severe skeletal Class
      III malocclusion, condyles remove posteriorly from more anterior position to
      normal concentric position, and temporo-mandibular disorders symptom is relieved
      and cured effectively.

PMID- 18072561
TI  - [Study on the relationship between function of blood and tumor recurrence in oral
      squamous cell carcinomas].
AB  - OBJECTIVE: To explore the coagulation indexes and offer a valuable reference for
      clinic therapy and prognosis in patients with oral squamous cell carcinomas
      (OSCCs). METHODS: The indexes of prothrombin time (PT), activated partial
      thromboplastin time (APTT), thrombin time (TT) and fibrinogen (Fib) were detected
      by using automatic blood coagulation testing machine in 65 healthy people and 351
      patients with OSCCs. All patients with OSCCs were divided into three groups
      included primary tumor, neck metastasis of lymph nodes and recurrence. The data
      were analysed by SPSS 11.0. RESULTS: The index of PT in patients with OSCCs was
      longer than that of healthy people. There was a significance between the control
      group and the group with the neck metastasis of lymph node or the recurrence
      group (P<0.01). The time of APTT was shortened. Except for the group with the
      neck metastasis of lymph node and the recurrence group the distinctive difference
      existed in other groups(P<0.05). There was no significance between two groups in
      the indexes of TT and Fib (P>0.05). CONCLUSION: PT and APTT may be the useful
      indexes for clinic therapy and prognosis in patients with oral squamous cell
      carcinomas.

PMID- 18072562
TI  - [Distribution of five periodontal pathogens in subgingival plaque in chronic
      periodontitis].
AB  - OBJECTIVE: To investigate the distribution of H. actinomycetemcomitans, P.
      gingivalis, P. intermedia, T. forsythensis and T. denticola in the subgingival
      plaque in the patients with chronic periodontitis. METHODS: 27 patients with
      chronic periodontitis were included. Two of the deepest pockets of each patient
      were selected as the study sites. Semi-quantification of subgingival
      microorganism samples was analyzed by multiplex polymerase chain reaction and
      reverse hybridization assay. RESULTS: P. gingivalis, P. intermedia, T.
      forsythensis and T. denticola were detected in a high proportion of examined
      sites(corresponding values were 98.15%, 92.59%, 100% and 98.15%), however, the
      proportion of H. actinomycetemcomitans was low (20.37%). The levels of P.
      gingivalis and T. forsythensis were higher than the other three microorganisms
      with statistical significance. CONCLUSION: The simultaneous infection of P.
      gingivalis, T. forsythensis, P. intermedia and T. denticola is found in the
      patients with chronic periodontitis, in which the levels of P. gingivalis and T.
      forsythensis are higher than the other two microorganisms.

PMID- 18072563
TI  - [Study on color matching of equal volume in dental ceramic prothesis materials].
AB  - OBJECTIVE: To study the color changes on brightness and hue in dental ceramic
      prothesis materials. METHODS: The different color mark of VINTAGE series was
      sintered on 15 pieces Ni-Cr alloy denture materials. The sample group and control
      group was given the sintering of color blending with equivalent volume. The order
      of color mark was of A1 and A2, A2 and A3, A3 and A4, B1 and B2, B2 and B3, B3
      and B4 in sample group, and A1, A2, A3, A3.5, A4, B1, B2, B3 and B4 orderly in
      control group. The chromatic analysis on samples of VITA had been taken through
      applying PR 650 spectrum detector and adopted the statistic software of Photo
      Research and SPSS 12.0 for analysis. RESULTS: The statistical difference (P<0.05)
      of L*a*b* value was found in the different color mark of the same color serials.
      A non-linearity relation had been found in the chromatic parameters a*b*. It
      means the change of color was visible. CONCLUSION: Set A has a bigger grading
      change of brightness than Set B. The change of red-green is obviously in Set A,
      as well as yellow-blue in Set B.

PMID- 18072564
TI  - [Influence of ambient light and adjacent tooth in anterior tooth color
      measurement].
AB  - OBJECTIVE: To investigate the influence of different intensity and directions of
      ambient light and adjacent tooth in anterior tooth color measurement by using
      colorimeter. METHODS: Fiber lite MI-150 was used as ambient illuminant and it
      irradiated from three or twelve o'clock direction through 45 degrees angle above.
      The light magnitude 0, 50, 75, 100, 125, 150 W were applied in this experiment.
      The values of CIE L* a* b* were measured by Minolta Chroma meter CR-321
      colorimeter on the center labial surface of ten extracted human maxillary central
      incisors with or without adjacent teeth, then those data were analyzed
      statistically by using SPSS 11.5. RESULTS: Neither different intensities nor
      different directions of ambient light could influence the results of color
      measurement by using Minolta Chroma meter CR-321 colorimeter, so did the adjacent
      teeth whether those were exist or not. CONCLUSION: There is no influence of
      ambient light and adjacent teeth in the color measurement of anterior teeth under
      this experiment condition, and Minolta Chroma meter CR-321 colorimeter can be
      used to measure the color directly aside the chair with light.

PMID- 18072565
TI  - [Study on the matching of the shade between beverage and modifying porcelain
      shade guide].
AB  - OBJECTIVE: To evaluate the matching of the shade between beverage and modifying
      porcelain shade guide according to Munsell color order system, thus to provide
      the reference basis for selecting modifying porcelain to mimic the stain of
      natural tooth by technician. METHODS: The shade of Vita Akzent, Vita Interno,
      Shofu Vintage & Unibond and Noritake Super Porcelain EX-3 shade tabs as well as
      15 kinds of beverage were measured according to Munsell color order system on
      Color-Eye 7000A spectrophotometer. The difference of the frequency of approximate
      hue, value, and chroma between shade tabs and beverage were compared by
      calculating the Fisher exact probabilities. RESULTS: The frequency of approximate
      hue between 4 kinds of shade tabs and 15 kinds of bev-erage was significant
      different (P<0.05), while the frequency of approximate value, and chroma was not
      significant different (P>0.05). CONCLUSION: Except the hue, the color
      distribution of 4 kinds of shade tabs was similar to that of 15 kinds of
      beverage. But the color of beverage also can be approximately matched by any kind
      of modifying porcelain by mixing porcelain powder of appropriate hue, value, and
      chroma.

PMID- 18072566
TI  - [Clinical evaluation of two types of fixed partial denture impressions].
AB  - OBJECTIVE: To evaluate the clinic effects of alginate impression and
      agar/alginate combined impression. METHODS: 237 patients of fixed partial denture
      were collected and divided into group A and group B. Group A was taken impression
      by aglinate impression, including 81 patients (207 abutments). Group B was taken
      impression by agar/alginate combined impression, include 156 patients (392
      abutments). The impressions were observed by megaloscope, and the number of
      abutment, the types and number of defect were recorded. RESULTS: In the aglinate
      impressions, 57.0 percent of abutment had some defect. But in the agar/alginate
      combined impressions, 36.0 percent of abutment had some defect. There were
      significant difference between group A and group B in the abutment, air bubbles
      in cervical margin, unsharpness of the gingival sulcus and shoulders (P<0.05).
      There were no significant difference between group A and group B in the split and
      defect of the impressions on the cervical margin. CONCLUSION: There were less
      defects in the agar/alginate combined impression than in the alginate impression.

PMID- 18072567
TI  - [Cloning of human bone morphogenetic protein-2 gene and the construction of its
      eukaryotic expression vector].
AB  - OBJECTIVE: To clone human bone morphogenetic protein-2 (hBMP2) gene and construct
      its eukaryotic expression vector pcDNA3.1 -hBMP2. METHODS: Human BMP2 gene was
      amplified by RT-PCR method from human osteosarcoma cells and constructed into
      eukaryotic expression vector pcDNA3.1-hBMP2. The gene in the vector pcDNA3.1
      hBMP2 was identified by PCR amplification, enzyme digestion and DNA sequencing.
      RESULTS: The cloned DNA was confirmed to be hBMP-2 gene. CONCLUSION: In this
      study, hBMP2 gene is successfully cloned and its eukaryotic expression vector
      pcDNA3.1-hBMP2 is constructed, which provides the foundation of using BMP2 gene
      therapy to accelerate new bone formation in distraction osteogenesis.

PMID- 18072568
TI  - [Effect of oral carcinoma-associated fibroblasts on extracellular signal
      regulated kinases pathway in the lingual carcinoma cell line].
AB  - OBJECTIVE: To investigate the effects of oral carcinoma-associated fibroblasts
      (CAFs) on extracellular signal-regulated kinases (ERK) pathway in a lingual
      carcinoma cell line. METHODS: The lingual carcinoma cell line, Tca8113 was
      stimulated by conditioned medium from oral CAFs, or cocultured with oral CAFs for
      definite time. Total ERK and pERK in Tca8113 lysate were detected by Western
      blotting, and the ratio between pERK and ERK were calculated. RESULTS: Both
      stimulation by conditioned medium and coculture induced prompt phosphorylation of
      ERK, and increased the ratio between pERK and ERK. CONCLUSION: Oral CAFs can
      activate ERK pathway of carcinoma cells.

PMID- 18072569
TI  - [Photoelastic analysis of movement tendency of lower teeth using multiloop
      edgewise archwire with vertical elastics in anterior teeth area].
AB  - OBJECTIVE: To investigate the movement tendency of lower teeth using multiloop
      edgewise archwire (MEAW) with vertical elastics in anterior teeth area by three
      dimensions photoelastic analysis. METHODS: The photoelastical model of full teeth
      as human body on physical parameter and dimension was established and loaded by
      MEAW with vertical elastics in anterior teeth area similar with clinic. Every
      freezing model-tooth was bladed by anteroposterior axes and vertical axes, the
      stress of every point of alveolar bone was calculated by three-dimensions shear
      equation method. The stress distribution regularity of per-tooth was analyzed to
      describe their move tendency. RESULTS: The lower second molar was intrused and
      rotated to distal and inclined as negative torque. The lower first molar moved
      and rotated to distal, the mesial rotate to buccally and the distal rotate to
      lingually. The lower second pre-molar was extruded and inclined as crown to
      mesial and root to distal, inclined as negative torque. The lower canine was
      intrused slightly and inclined as positive torque. The lower lateral incisor was
      extruded and moved and inclined as positive torque. CONCLUSION: Using MEAW with
      several "L" loop can control the movement of every tooth in three dimension.

PMID- 18072570
TI  - [Influence of orthodontic force on osteoprotegerin and osteoprotegerin ligand
      mRNA expression in the inflammatory periodontal tissues].
AB  - OBJECTIVE: To explore certain principle of how osteoprotegerin (OPG) and
      osteoprotegerin ligand (OPGL) take part in the periodontal tissues remodeling
      under the combined influence of inflammation and orthodontic force. METHODS: The
      positive signals of OPG and OPGL mRNA were measured with in situ hybridzation
      after orthodontic tooth movement in the experimental periodontitis groups and
      control ones. RESULTS: The OPG and OPGL mRNA expression intensity in the
      experimental group showed difference from control. All their optical density
      index reached a peak in day 2, respectively. CONCLUSION: OPG and OPGL play
      important roles in the periodontal reconstruction induced by inflammation
      irritation and orthodontic force, and complex interaction could exist between the
      two factors.

PMID- 18072571
TI  - [Analyses of differential expression of Homeobox genes between lingual squamaous
      cell carcinoma and normal mucosa].
AB  - OBJECTIVE: To investigate the differently expressed Homeobox genes between
      lingual squmaous cell carcinoma and normal mucosa. METHODS: Seven paired
      specimens including lingual squmaous cell carcinoma and its surrounding normal
      tissue were obtained from 7 patients. Customized Oligo microarray which contains
      numerous probes of 232 human Homeobox genes was used to analyse the results. All
      datas were scanned by Agilent scanner and differentiately expressed genes were
      sorted out. RESULTS: Homeobox gene NANOG was found up-regulated in 5 samples.
      PHTF2 was found down-regulated in 7 samples, and CRX, PITX1, OTEX was found down
      regulated in 5 samples. CONCLUSION: As the key gene to cellular proliferation and
      differentiation, Homeobox genes is closely releverant to the oncogenesis of
      lingual squmaous cell carcinoma.

PMID- 18072572
TI  - [Ectopic bone induction in vivo after transplantation of skeletal satellite cells
      from green fluorescence protein transgenic mouse transfected by adenoviral
      vectors encoding bone morphogenetic protein-2].
AB  - OBJECTIVE: To observe the ability of induced ectopic bone using skeletal muscles
      satellite cells (SMSCs) from newborn green fluorescence protein (GFP) transgenic
      mice mediated by Ad-BMP2. METHODS: Transplantation of SMSCs transduced with Ad
      BMP2 into back lamb muscles of subfascia in wildtype 129sv mice with a complex of
      collagen scaffords, then the tissue histologic examination, X ray plain film,
      fluorescence microscopy were used. RESULTS: Transplantation of SMSCs transfected
      with Ad-BMP2 into back lamb muscles of subfascia generated ectopic bone formation
      involving GFP-positive osteoblasts and osteocytes 2 weeks and mature bone
      formation 4 weeks after transplantation. SMSCs non-transfected with Ad-BMP2
      failed to induce ectopic bone formation. CONCLUSION: SMSCs retain differentiation
      potentitality into osteoblasts in response to Ad-BMP2. They are useful tools for
      analyzing the process of osteoblast differentiation in vivo after
      transplantation.

PMID- 18072573
TI  - [Effect on induction of differentiation of Tca8113 cells affected by abscisic
      acid in vitro].
AB  - OBJECTIVE: To approach the effects on induction of differentiation of Tca8113
      cells affected by abscisic acid. METHODS: The changes of surface differentiation
      markers, cell configuration, restrain of cell growth and the expression of
      Caspase-3 mRNA were examined by using inverted-phase contrast microscope,
      immunohistochemistry (IHC) and in situ hybridization in vitro. The dependablity
      between the surface differentiation markers and Caspase-3 mRNA was analysed.
      RESULTS: The restraint of cell growth in ABA groups was higher than that of the
      control group (P<0.05). There was a trend that the tumor cell had transformed the
      normal cell. Furthermore, the time-dosage dependent relationship existed in the
      inhibition rate of tumor cells. The results showed that the expressions of
      Involucrin protein, retinoic acid receptor beta (RARbeta) and Caspase-3 mRNA in
      experimental group had been higher than that of control group. There was a
      significance between the different concentration experimental groups at 24 h
      (P<0.05). Moreover, the positive correlation existed among the Involucrin,
      RARbeta and Caspase-3 mRNA at the time of 12 hour and 24 hour (P<0.05).
      CONCLUSION: The possible mechanism is that abscisic acid acted on the tumor cell
      and raised the level of RARbeta gene through combining the correlative receptors
      so that increased the expression of Involucrin protein and promoted the activity
      of Caspase-3 and resulted in apoptosis of tumor cell.

PMID- 18072574
TI  - [Effect of vacuum deposition technology on the metal-porcelain bond strength of a
      new type of CO-CR ceramic and framework dental alloy].
AB  - OBJECTIVE: To investigate the effect of a new engineering technique of vacuum
      deposition-plasma magnetron reactive sputter deposition technique on the metal
      porcelain bond strength of a new type of Co-Cr ceramic and framework dental
      alloy. METHODS: Before porcelain painted on the specimens, the standardized metal
      strips made from DA9-4 dental alloy were coated with a thin Al2O3 ceramic film by
      plasma magnetron reactive sputter deposition technique. The conformation,
      structure and thickness of the ceramic film were analyzed. The specimens for
      three-point bending test made from DA9-4 alloy and VMK95 porcelain were used for
      metal-porcelain bond strength measurement, in the same time the interface of
      metal-porcelain and element distribution were also observed. RESULTS: The
      flexural bonding strength of metal-porcelain of sputtering group and control
      group were (180.55+/-16.45) MPa and (143.80+/-24.49) MPa. The flexural bonding
      strength of metal-porcelain of sputtering group was higher than control group
      significantly through statistical analysis (P<0.01). CONCLUSION: The plasma
      magnetron reactive sputter deposition technique has a positive effect in
      improving the bonding strength of DA9-4 dental alloy and ceramic.

PMID- 18072575
TI  - [Clinical and pathologic features of Letterer-Siwe disease: a case report and
      review].
AB  - Letterer-Siwe disease (LSD) is a kind of a histiocytosis, rarely seen in clinic.
      However, its prognosis is poor. A case of LSD which complaints of the oral ulcer
      is reported in this article. The patient of the case was a boy, came to hospital
      on July 5, 2003 because of oral ulcers, teeth loosing and falling off for a
      month, and pus running over from both antra auris for two weeks. No familial
      history of genetic diseases and special infections were found. The case consisted
      of the following features after exam: Erythematous papules and petechia dotted in
      the skin, primarily on scalp and trunk, two ears suffering otitis media, oral
      proliferative ulcers appearing in palate and lower gingival accompanying with the
      lower teeth loosing in the lesion area, in the meantime, the destruction of
      madibula on the left side also found out by X-ray, hepatic dysfunction and poor
      cellular immunity coming along with pertinacious candidosis. The pathologic exam
      showed histioid cell infiltration, and the immunohistochemical exam showed
      CDla(+), S-100(+). Diagnosis defined it LSD. According to the case's character
      and literature review, the clinical features, diagnosis and therapy of LSD were
      discussed.

PMID- 18072576
TI  - [Two sides of sublingual glands swelled following the ill fitting prosthesis
      used: a case report].
AB  - The patient visited for swell and ache of sublingual region. The patient's two
      sides of sublingual glands were swelled. The mandibular central incisors were
      repaired by the ill fitting prosthesis, and there was an irregular oral ulcer
      under it. The area of the ulcer was about 2 mm x 2 mm. The sublingual glands
      recovered in two days after the ill fitting prosthesis of mandibular central
      incisors was removed away, iodoglycerin was applied on the oral ulcer, vitamin
      B1, vitamin B2, prednisone and amoxicillin was taken.

PMID- 18072577
TI  - [Hemoptysis. Clinical picture].

PMID- 18072578
TI  - [What is your diagnosis? Pityriasis rosea Gibert].

PMID- 18072579
TI  - [Diagnosis: meanders and shortcuts].
AB  - Diagnosis is knowing about the probability of an illness in a particular patient.
      Relevant steps in establishing a diagnosis are: gathering of information (history
      and results of physical examination), defining attributes, to mentally represent
      the clinical problem and to compare it with memorized illness scripts. From this
      follows a list of potential illnesses which could explain the clinical signs and
      symptoms. The next step is to distill the most likely diagnosis by gathering
      further information about the patient. Most diagnostic errors occur during the
      information gathering and by interpreting the information.

PMID- 18072580
TI  - [Severity of COPD--a broader prognostic assessment is necessary].
AB  - Clinical manifestations of chronic obstructive pulmonary disease (COPD) and
      progress of disease are heterogeneous. A single parameter such as lung function
      is insufficient to capture manifestations of COPD and to estimate the prognosis
      of patients. A number of additional parameters such as level of physical
      activity, cardiovascular co-morbidity or history of exacerbations should be
      considered. If a validated assessment including the most important prognostic
      parameters becomes available, COPD management could become more individualized
      and patient-centered than it currently is.

PMID- 18072581
TI  - [Psychogeriatric emergency house call].

PMID- 18072582
TI  - [Weight loss and night sweats with unexpected tumor localization].
AB  - A 52-year-old patient presented himself with weight loss and night sweats.
      Laboratory analyses revealed a high sedimentation rate, elevated immunoglobulines
      and anaemia with sludge phenomenon. Differential diagnoses included Multiple
      Myeloma and Lymphoma. Having a risk constellation for HIV infection and just
      having recovered from oral thrush also made this diagnosis possible. Urinary
      analysis and chest x-ray were normal; however, CT-scan detected renal cell cancer
      with pulmonary metastases. Renal cell cancer is heterogeneous in presentation,
      symptoms are unspecific, therefore they are often discovered late when they have
      already metastasized. Paraneoplastic syndromes, e.g. hypercalcaemia or
      hypertension are not infrequent in renal cell cancer.

PMID- 18072583
TI  - Things that go 'bump' in the house.

PMID- 18072584
TI  - Tissue engineering.

PMID- 18072585
TI  - MudPIT: multidimensional protein identification technology.
AB  - Large-scale biology emerged out of the efforts to sequence genomes of important
      organisms. Based on resources created by whole genome sequencing, large-scale
      analyses of messenger RNA (mRNA) and protein expression are now possible. With
      the availability of large amounts of genomic sequence information, a convenient
      method for the identification and analysis of proteins based on proteolytic
      digestion into peptides emerged. Processes to fragment peptides using collision
      activated dissociation (CAD) in tandem mass spectrometers and computer algorithms
      to match the tandem mass spectra of peptides to sequences in databases enable
      rapid identification of amino acid sequences, and hence proteins, present in
      mixtures. The inherent complexity of the peptide mixtures has necessitated
      improvements in methodology for mass spectrometry (MS) analysis of peptides.

PMID- 18072586
TI  - The costs of using unauthenticated, over-passaged cell lines: how much more data
      do we need?
AB  - Increasing data demonstrate that cellular cross-contamination, misidentified cell
      lines, and the use of cultures at high-passage levels contribute to the
      generation of erroneous and misleading results as well as wasted research funds.
      Contamination of cell lines by other lines has been recognized and documented
      back to the 1950s. Based on submissions to major cell repositories in the last
      decade, it is estimated that between 18% and 36% of cell lines may be
      contaminated or misidentified. More recently, problems surrounding practices of
      over-subculturing cells are being identified. As a result of selective pressures
      and genetic drift, cell lines, when kept in culture too long, exhibit reduced or
      altered key functions and often no longer represent reliable models of their
      original source material. A review of papers showing significant experimental
      variances between low- and high-passage cell culture numbers, as well as
      contaminated lines, makes a strong case for using verified, tested cell lines at
      low- or defined passage numbers. In the absence of cell culture guidelines,
      mandates from the National Institutes of Health (NIH) and other funding agencies
      or journal requirements, it becomes the responsibility of the scientific
      community to perform due diligence to ensure the integrity of cell cultures used
      in research.

PMID- 18072587
TI  - Optimization of HIV-1 infectivity assays.
AB  - HIV-1 reporter cell lines are the backbone of diagnostic assays, vaccine and drug
      development efforts. Performing HIV-1 infection experiments in a T cell
      background is desirable for many reasons. However, a low susceptibility to
      infection with primary patient isolates in available reporter T cell lines has
      limited such efforts. We here demonstrate that optimization of HIV-1 receptor
      expression and the utilization of serum free medium compositions can increase
      susceptibility of reporter T cell lines to HIV-1 infection by up to two orders of
      magnitude.

PMID- 18072588
TI  - Cognate putative nuclear localization signal effects strong nuclear localization
      of a GFP reporter and facilitates gene expression studies in Caenorhabditis
      elegans.
AB  - Targeting a gene expression reporter, usually the green fluorescent protein
      (GFP), to the nucleus via a translationally fused nuclear localization signal
      (NLS) greatly facilitates recognition and identification of the reporter
      expressing cells in Caenorhabditis elegans. Presently circulating nematode
      transcriptional gene expression vectors use the viral NLS from simian virus 40
      (SV40) large T antigen. This NLS, however fails to ensure sufficient localization
      of the GFP peptide to the nucleus. We modified the common transcriptional
      reporter SV40 NLS-GFP by adding to its C terminus a cognate putative NLS from the
      transcription factor egl-13. The EGL-13 NLS effected clear contrast in
      fluorescence intensity between the nucleus and the cytoplasm in cells with strong
      reporter signal and efficiently highlighted the nucleus in tissues with weak
      reporter expression in a wide range of tested tissues. The SV40 NLS-GFP-EGL-13
      NLS vector should become a valuable tool for gene expression studies in C.
      elegans.

PMID- 18072590
TI  - Method for isolation of PCR-ready genomic DNA from zebrafish tissues.
AB  - Here we describe a method for the isolation of PCR-ready genomic DNA from various
      zebrafish tissues that is based on a previously published murine protocol. The
      DNA solutions are of sufficient quality to allow PCR detection of transgenes from
      all commonly used zebrafish tissues. In sperm, transgene amplification was
      successful even when diluted 1000-fold, allowing easy identification of
      transgenic founders. Given its speed and low cost, we anticipate that the
      adoption of this method will streamline DNA isolation for zebrafish research.

PMID- 18072589
TI  - Continuous enzymatic assay for histone lysine methyltransferases.
AB  - We describe a continuous peptide methylation assay using the Neurospora crassa
      Dim-5 histone H3 lysine 9 (H3K9) methyltransferase as a model system. The assay
      uses streptavidin FlashPlates coated with target peptide. Since no washing and
      pipeting steps were required after the addition of the enzyme/S-adenosyl-L
      methionine (AdoMet) mixture to the microplate, a continuous readout of the
      reaction progress was possible. We show that this assay is highly reproducible
      (with errors in the order of +/- 3%). The continuous assay is well suited for the
      simultaneous analysis of up to 384 samples, thus allowing for a rapid screening
      of methylation rates of different substrates under different conditions or in the
      presence of inhibitors.

PMID- 18072591
TI  - Nucleobase analogs for degenerate hybridization devised through conformational
      pairing analysis.
AB  - A conformational pairing analysis was used to devise nucleobase analogs capable
      of forming nonselective and energetically favorable base pairs opposite either
      the purine or the pyrimidine constituents of nucleic acids. 5-methylisocytosine
      and isoguanine were conceived as a degenerate pyrimidine and a degenerate purine,
      respectively. Data from previous DNA duplex melting experiments verified that the
      analogs can act as degenerate nucleobases as hypothesized. Isoguanine also formed
      unusually stable base pairs with guanine. A quantitative PCR assay yielding
      equivalent results across hepatitis C virus (HCV) subtypes was created with this
      system, despite the use of a single probe targeted to a polymorphic region.
      Amplification curves using probes with 5-methylisocytosine or isoguanine opposite
      appropriate ambiguous target positions exhibited more signal than curves from
      similar probes containing common degenerate nucleobase hypoxanthine.

PMID- 18072592
TI  - Measurement of quantity of iron in magnetically labeled cells: comparison among
      different UV/VIS spectrometric methods.
AB  - Cell labeling with superparamagnetic iron oxides (SPIO) is becoming a routine
      procedure in cellular magnetic resonance imaging (MRI). Quantifying the
      intracellular iron in labeled cells is a prerequisite for determining the number
      of accumulated cells by quantitative MRI studies. To establish the most sensitive
      and reproducible method for measuring iron concentration in magnetically labeled
      cells, we investigated and compared four different methods using an ultraviolet
      visible (UV/VIS) spectrophotometer. Background spectra were obtained for 5 and 10
      M hydrochloric acids, a mixture of 100 mM citric acid plus ascorbic acid and
      bathophenanthroline sulphonate (BPS), and a mixture of 5 M hydrochloric acid plus
      5% ferrocyanide. Spectra of the same solutions containing either 10 or 5
      microg/mL iron oxides were also created to determine the peak absorbance
      wavelengths for the dissolved iron. In addition, different known iron
      concentrations were used to obtain calibration lines for each method. Based on
      the calibration factors, iron was measured in samples with a known amount of iron
      and in labeled cells. Methods based on the use of 10 M hydrochloric acid
      underestimated iron concentration in all experiments; for this method to give an
      accurate measurement, iron concentration in sample needs to be at least 3
      microg/mL.

PMID- 18072593
TI  - Expression profiling of archival renal tumors by quantitative PCR to validate
      prognostic markers.
AB  - Formalin-fixed paraffin-embedded (FFPE) tissues are routinely stored by most
      pathology departments and are a widely available resource for discovery of
      clinically useful biomarkers. We describe our method for optimizing quantitative
      reverse transcription PCR (RT-PCR) for expression analysis using frozen and
      archival tissue. Commonly used reference genes were evaluated for stability of
      expression in normal kidney and clear cell renal cell carcinoma (RCC). Optimal
      reference genes for calculating normalization factors for RT-PCR were ACTB,
      RPL13A, GUS, RPLP0, HPRT1, and SDHA when using FFPE RCC. The optimal reference
      genes when using frozen RCC were ACTB, RPL13A, and GUS, confirming that use of
      multiple reference genes improves accuracy when intact RNA from frozen renal
      tumors are used. Expression of 16 markers previously reported to have prognostic
      significance in RCC was determined in 23 matching frozen and FFPE renal tumors,
      representing a range of tumor grades and stages; correlation coefficient for
      expression measured in frozen and FFPE tumors was 0.921 (P < 0.001). All markers
      predicted survival when frozen tumors were used and 14 of the 16 markers
      predicted survival when FFPE tumors were used as the source of RNA. An optimized
      RT-PCR assay can accurately measure expression of most prognostic tumor markers.

PMID- 18072594
TI  - High-efficiency thermal asymmetric interlaced PCR for amplification of unknown
      flanking sequences.
AB  - Isolation of unknown DNA sequences flanked by known sequences is an important
      task in molecular biology research. Thermal asymmetric interlaced PCR (TAIL-PCR)
      is an effective method for this purpose. However the success rate of the original
      TAIL-PCR needs to be increased, and it is more desirable to obtain target
      products with larger sizes. Here we present a substantially improved TAIL-PCR
      procedure with special primer design and optimized thermal conditions. This high
      efficiency TAIL-PCR (hiTAIL-PCR) combines the advantages of the TAIL-cycling and
      suppression-PCR, thus it can block the amplification of nontarget products and
      suppress small target ones, but allow efficient amplification of large target
      sequences. Using this method, we isolated genomic flanking sequences of T-DNA
      insertions from transgenic rice lines. In our tests, the success rates of the
      reactions were higher than 90%, and in most cases the obtained major products had
      sizes of 1-3 kb.

PMID- 18072596
TI  - Applications of a microplate reader in yeast physiology research.
AB  - Microplate readers have been useful assistants of researchers for several
      decades. This work is focused on the applications of a simple absorbance
      microplate reader in yeast physiology research, and its advantages and
      limitations in comparison with alternative methods are discussed. The two main
      procedures involved are measuring growth curves and monitoring the pH changes of
      medium using two different pH indicators. We suggest mathematical formulas for
      converting absorbance data into pH values. With a microplate reader as many as 96
      samples can be simultaneously analyzed, while medium consumption is minimized to
      100 microL per sample. The results can be observed in 24-48 h (for growth curves)
      or in 1-3 h (for pH changes) with minimal hands-on time required.

PMID- 18072595
TI  - PhiC31-mediated cassette exchange into a bacterial artificial chromosome.
AB  - The use of bacterial artificial chromosomes (BACs) modified via homologous
      recombination in Escherichia coli has become a powerful tool in the transgenic
      field. Homologous recombination allows the manipulation of BACs in very different
      ways. However this process can be cumbersome and problematic when using large
      targeting constructs containing several repeated elements. In order to address
      this problem, we have established a phiC31 integrase-mediated cassette exchange
      into a BAC. As an example of this technique, we have exchanged a cassette
      previously recombined into a BAC containing the Rosa 26 locus, by a 16.5-kb
      incoming construct containing several repeated elements. The combination of
      homologous recombination in E. coli and cassette exchange should expand the tools
      for manipulating BACs, thus facilitating the generation of constructs with higher
      complexity.

PMID- 18072597
TI  - Long-term storage of DNA-free RNA for use in vaccine studies.
AB  - RNA replicons represent potential vaccine delivery vehicles, but are considered
      too unstable for such use. This study examined the recovery, integrity and
      function of in vitro transcribed replicon RNA encoding hepatitis C virus (HCV)
      proteins. To remove residual template DNA, the RNA was digested with TURBO DNase
      followed by RNeasy DNase set and purified through an RNeasy column. The RNA was
      freeze-dried in distilled water or trehalose, stored under nitrogen gas for up to
      10 months and analyzed at different time points. The recovery of RNA stored at <
      or = 4 degrees C that was freeze-dried in distilled water varied between 66% to
      zero of that recovered from RNA freeze-dried in 10% trehalose, a figure that
      depended on the duration of storage. In contrast, the recovery of the RNA stored
      in trehalose was consistently high for all time points. After recovery, both RNAs
      were translationally competent and expressed high levels of proteins after
      transfection, although the level of expression from the trehalose-stored RNA was
      consistently higher. Thus the addition of trehalose permitted stable storage of
      functional RNA at 4 degrees C for up to 10 months and this permits the
      development of RNA vaccines, even in developing countries where only minimum
      storage conditions (e.g., 4 degrees C) can be achieved.

PMID- 18072599
TI  - [Rationing in the Swiss health system and the elderly: time for action!].

PMID- 18072598
TI  - MethylScreen: DNA methylation density monitoring using quantitative PCR.
AB  - Aberrant gene silencing of genes through cytosine methylation has been
      demonstrated during the development of many types of cancers including prostate
      cancer Several genes including GSTP1 have been shown to be methylated in prostate
      cancer leading to the suggestion and demonstration that methylation status of
      such genes could be used as cancer diagnosis markers alone or in support of
      histology. We developed a bisulfite-free alternative, MethylScreen technology, an
      assay for DNA methylation detection utilizing combined restriction from both
      methylation-sensitive restriction enzymes (MSRE) and methylation-dependent
      restriction enzymes (MDRE). MethylScreen was used to analyze the 5' region of
      GSTP1 in cell lines, in vitro methylated DNA populations, and flash-frozen tissue
      samples in an effort to characterize the output and analytical performance
      characteristics of the assay. The output from the quantitative PCR assay
      suggested that it could not only detect fully methylated molecules in a mixed
      population below the 1% level, but it could also quantify the abundance of
      intermediately methylated molecules. Interestingly, the interpreted output from
      the four quantitative PCRs closely resembled the molecular population as
      described by clone-based bisulfite genomic sequencing.

PMID- 18072600
TI  - [Management of elderly patients with delirium or dementia in Swiss nursing
      homes].
AB  - Management of elderly patients with delirium or dementia in Swiss nursing homes
      Dementia and delirium are among the most frequent medical conditions in older
      nursing home residents. Their management require a coordinated interdisciplinary
      approach, including for drug prescription. Using a systematic literature review
      of published meta-analyses and guidelines, prescription algorithms were developed
      adressing the pharmacological management of cognitive symptoms of dementia and
      delirium in older nursing home residents in the canton of Fribourg.

PMID- 18072601
TI  - [Post-fall syndrome: how to recognize and treat it?].
AB  - The post-fall syndrome is commonly observed in geriatric medicine, affecting near
      one out of five fallers. Left untreated, this condition can lead to a regressive
      syndrome, with physical, psychological and social consequences. To avoid such an
      evolution, specific physical therapy must be proposed as soon as possible. In
      this paper, clinical presentation and management of the post-fall syndrome are
      discussed.

PMID- 18072602
TI  - [Insomnia in the elderly].
AB  - In older persons, insomnia is a frequent problem with significant functional and
      psychological consequences. Use of over-the-counter medications is frequent and
      increases the risk of adverse events. Management of insomnia is based on a
      systematic evaluation that leads to targeted etiologic treatment when feasible.
      Non-pharmacological approach, including sleep hygiene and cognitive-behavioral
      therapy, remains effective in older persons. Hypnotics use remains nevertheless
      highly prevalent among elderly patients and withdrawal should be attempted after
      informing these patients of these drugs numerous side-effects.

PMID- 18072603
TI  - [How to increase the necropsy rate in hospital?].
AB  - The autopsy serves to identify the causes of a patient's death. For some years it
      is undergoing an important decline but nevertheless the post-mortem examination
      remains one of the basic tools for the assessment of medical care. The aim of
      this paper is to detect the reasons for the decline of this practice, to review
      the contribution of autopsy to medicine and to analyze the effects of physicians
      training at the request of autopsy to boost this practice.

PMID- 18072604
TI  - [Population health profile at the age of 65-70].
AB  - Despite the promise of a large number of baby-boomers soon reaching the age of
      65, little is known regarding the population health in the 65-70 years age group.
      Baseline data from the Lausanne cohort Lc65+, representative of the community
      dwelling population born before the first world war, indicate that most
      individuals aged 65-70 have medical diagnoses of chronic diseases; many present
      comorbidities and geriatric syndromes are already present in a sizable
      proportion. However, the prevalence of dependence in basic activities of daily
      living is still low. This health profile points to the appropriateness of
      geriatric assessments from the age of 65 and to a potential for prevention of
      unfavourable outcomes in later life.

PMID- 18072605
TI  - [Paced right bundle branch block: what to do?].
AB  - Left bundle branch block (LBBB) is the assumed presentation of right ventricular
      pacing. Paced right bundle branch block (RBBB) raises the suspicion of lead
      malposition. In a well placed right ventricular lead an atypical conduction
      pattern must be evoked. It is important to differentiate malposition from well
      placed ventricular lead because malposition is associated with embolic
      complications and may require therapeutic interventions including anticoagulation
      or radical lead replacement. We report the case of two patients with a paced RBBB
      pattern despite a well-placed right ventricular lead, as confirmed by chest X-ray
      and echocardiography. We discuss the etiologies and attitude to adopt when
      electrocardiogram (ECG) shows a paced RBBB.

PMID- 18072606
TI  - [Assisted suicide: elements of considerations for medical practitioners].

PMID- 18072607
TI  - [The brain as an open book].

PMID- 18072608
TI  - [Blue tongue disease: mystery and hope (I)].

PMID- 18072609
TI  - [When art and science reason in resonance].

PMID- 18072610
TI  - [The examination of DNA and ethnic registration].

PMID- 18072611
TI  - [Andropause does not exist... but take care of yourself].

PMID- 18072612
TI  - [Preliminary version of the National Board of Health and Welfare's new guidelines
      for cardiac health care. Reliable knowledge material gives basis for better
      care].

PMID- 18072613
TI  - [Nephropathia epidemica: high risk in Norrland during winter].

PMID- 18072614
TI  - [Female urinary incontinence is investigated and treated in primary health care.
      Specialist care in complicated cases--without long waiting time].

PMID- 18072615
TI  - [Prostate-specific antigen--the most important cancer marker. Diagnostics and
      follow up of prostatic cancer have changed].

PMID- 18072616
TI  - [Funnel anus--a malformation requiring individualized management. The care should
      also be centralized].

PMID- 18072617
TI  - [It's healthy to have a cold! Apoteket wants to earn money on a normal
      inconvenience].

PMID- 18072618
TI  - [Psychiatric care--a constant punching bag?].

PMID- 18072619
TI  - [Low dosage CT better than conventional radiography in the diagnosis of
      rhinosinusitis--a comment from the Medical Products Agency and Strama].

PMID- 18072620
TI  - [Burnout syndrome--a societal phenomenon at a group level].

PMID- 18072621
TI  - [The principle of public access and integrity protection of research subjects-
      final comments].

PMID- 18072622
TI  - [The evolution after Erasmus and Charles Darwin not only progress].

PMID- 18072623
TI  - [Detection of common fusion transcript levels in untreated leukemia patients by
      real-time quantitative RT-PCR technique].
AB  - OBJECTIVE: To evaluate levels of common specific fusion transcripts M-bcr-abl, m
      bcr-abl, TEL-AML1, AML1-ETO, PML-RAR alpha, CBF beta-MYH11 in untreated leukemia
      patients. METHODS: Specific fusion transcript levels were detected by TaqMan
      based real-time quantitative RT-PCR technique in a total of 208 samples,
      including 195 bone marrow samples from 50 M-bcr-abl(+) chronic phase-chronic
      myeloid leukemia (CML-CP), 10 M-bcr-abl(+) acute lymphoblastic leukemia (ALL), 19
      m-bcr-abl(+) ALL, 11 TEL-AML1(+) ALL, 30 AML1-ETO(+) acute myeloid leukemia
      (AML), 58 PML-RAR alpha(+) acute promyelocytic leukemia (APL) and 17 CBF beta
      MYH11(+) AML patients and 13 peripheral blood samples from 13 M-bcr-abl(+) CML-CP
      patients. abl was chosen as internal control gene. Fusion transcript level was
      calculated as fusion transcript copies/abl transcript copies in percentage.
      RESULTS: Bone marrow and peripheral blood samples of CML-CP patients had similar
      M-bcr-abl fusion transcript levels (median 30% vs 35%, P > 0.05). M- and m-bcr
      abl (median 64% vs 54%) levels were similar in ALL patients (P > 0.05), M-bcr-abl
      level was significantly higher in ALL than CML-CP patients(P < 0.001). Median TEL
      AML1 level was 228% in ALL patients. Among AML patients, AML1-ETO level was
      significantly higher than CBF beta-MYH11 and PML-RAR alpha levels (median 388% vs
      145%, 388% vs 47%, all P < 0.001), CBF beta-MYH11 level was significantly higher
      than PML-RAR alpha level (P < 0.001). Fusion transcript levels of L-, V- and S
      type PML-RAR alpha were 45%, 44% and 55%, respectively. L-type was significantly
      lower than S-type (P = 0.04). CONCLUSIONS: Fusion transcript levels in untreated
      leukemia patients were different and patient-to-patient variations did exist.
      Detection of fusion transcript levels in untreated leukemia patients not only
      provides baseline for minimal residual disease monitoring and treatment
      evaluation but also enable the comparison in inter-laboratory data.

PMID- 18072624
TI  - [The effect of arsenic trioxide (As2O3) combined with BSO on K562/ADM cell and
      its mechanisms].
AB  - OBJECTIVE: To investigate the apoptosis-induction, P-glycoprotein (P-gp) and mdr1
      mRNA inhibition effects of arsenic trioxide (As2O3) and buthionine sulfoximine
      (BSO) on multidrug-resistant cell line K562/ADM cells, and to determine the
      relationship between intracellular GSH content and arsenic effect. METHODS:
      K562/ADM cells were treated with arsenic (0.5, 2.0, 5.0 micromol/L) alone or
      combined with BSO (100 micromol/L). The cell proliferating capacity was assessed
      with MTT assay, and cell apoptosis by Annexin V and propidium iodide (PI)
      staining. Intracellular GSH contents were measured using a glutathione assay kit
      by spectrophotometry. P-gp expression was determined by flow cytometry, and mdr1
      mRNA expression by semi-quantitative RT-PCR. RESULTS: The GSH contents in
      K562/ADM cell was (81.13 +/- 3.91) mg/g protein. After the GSH contents were
      degraded by BSO, the K562/ADM cell proliferating capacity was obviously inhibited
      and the cells were induced apoptosis in 24 hours by the combination of clinic
      dose arsenic group (0.5, 2.0 micromol/L) and BSO (100 micromol/L). The cell
      apoptosis rates at 48 hours in arsenic alone group and combination group were
      (59.29 +/- 6.01)% and (65.06 +/- 8.29)%, and at 72 hours were (82.15 +/- 9.28)%
      and (92.72 +/- 9.41)% retrospectively. At 48 hours, the mdr1 mRNA inhibition
      effect of the combination group was obviously stronger than that of high dose
      arsenic alone group. At 72 hours, the P-gp inhibition effect of the combination
      group (clinic dose arsenic group, 0.5, 2.0 micromol/L) was obviously stronger
      than that of high dose arsenic alone group (5.0 micromol/L). CONCLUSION: The
      intracellular GSH contents are closely correlated with the arsenic effect. The
      combination of conventional dose arsenic and BSO significantly induces K562/ADM
      cell apoptosis and inhibits P-gp and mdr1 mRNA expression in the cells.

PMID- 18072625
TI  - [Clinical study of 572 adult acute leukemia patients in Shanghai according to WHO
      classification].
AB  - OBJECTIVE: To evaluate WHO classification of acute leukemia (AL) in Shanghai and
      compare the difference between WHO and FAB classification. METHODS: Successive
      and unselected leukemia patients were referred to Sino-US Leukemia Cooperative
      Group of Shanghai from 2003 to 2006. A total of 572 adult AL cases were diagnosed
      and classified according to WHO and FAB classification. RESULTS: Of the 572 AL
      patients, 436 (76.2%) were diagnosed as acute myeloid leukemia (AML), 119 (20.8%)
      acute lymphoblastic leukemia (ALL). The AML and ALL percentage ratio was 3.66: 1.
      AML with recurrent cytogenetic abnormalities accounted for 35.3%, and with
      multilineage dysplasia for 13.1%, therapy-related AML accounted for 0.9%, and AML
      not otherwise categorized for 50.7%. The percentage of therapy-related AML in
      Shanghai was lower than that in the Western. B-ALL was the majority (84.9%) in
      ALL. According to FAB classification, AML-M4 was the most (38.5%) common subtype.
      The percentage of AML-M3 and M4 in Shanghai were higher than that in the Western,
      but that of AML-M, was lower. The incidence of karyotypic abnormalities in AML
      was 60.8%. The incidence of AML with t (15;17) was higher than that in the
      Western. Favorable cytogenetic risk group accounted for 30.6%, intermediate group
      for 51.5%, unfavorable group for 17.9% of AML. B-ALL with t (9;22) was 33.7%.
      CONCLUSIONS: The percentages of AML with t (15;17) and AML-M4 in Shanghai and the
      incidence of cytogenetic favorable group were higher than that in the Western. It
      was different in WHO classification and karyotypic abnormalities of AML between
      Shanghai and the Western. Comparing to the AL data of Shanghai Leukemia Group
      between 1984 and 1994, the percentage of AML-M4 was increased, but that of AML-M1
      and M5 were decreased.

PMID- 18072626
TI  - [Retrospective analysis of 41 childhood hemophagocytic syndrome].
AB  - OBJECTIVE: To investigate the clinical features of hemophagocytic syndrome (HPS)
      and to improve its recognition, early diagnosis and to reduce misdiagnosis.
      METHODS: A retrospective study was carried out to analyze the underlying
      diseases, clinical characteristics, laboratory findings and outcomes in 41
      patients with HPS. RESULTS: HPS was clinically characterized by prolonged fever
      (100%), hepatomegaly (97.6%), splenomegaly (95.1%), and other features including
      lymph adenopathy (65.9%), respiratory symptoms (53.7%), hydrops of multiple
      serous cavity (26.8%), jaundice (26.8%), central nervous system involvement
      (14.6%), alimentary tract hemorrhage (12.2%) and skin rash (12.2%). Laboratory
      data indicated that liver dysfunction was the most prominent feature (100%)
      mainly manifested with elevated liver enzymes and hypoalbuminemia, and the others
      were hemophagocytosis in bone marrow (92.7%), pancytopenia 70.7%), coagulation
      abnormalities (52.4%), DIC, hypertriglyceridemia and refractory hyponatremia. The
      underlying disease of infection (IAHS) was most common (63.4%), in which EBV-AHS
      was predominant, making up to 69.2%. Fourteen patients died, 11 of them with IAHS
      (nine were EBV-AHS) and the other 3 non-IAHS (one of them was malignant
      lymphoma). The case-fatality rate was increased with the elevated levels of LDH
      and AST, the correlation coefficient was 0.486 and 0.516 (P < 0.05),
      respectively. Logistic regression analysis showed that age < 3 years old, levels
      of LDH > 2000 U/L and AST level > 200 U/L were independent prognostic factors (P
      value was 0.031, 0.002 and 0.001, respectively). CONCLUSION: There are various
      underlying diseases and clinical manifestations for HPS. EBV-AHS is the extremely
      dangerous situation with high mortality. Age, levels of LDH and AST are the death
      associated risk factors. Repeat bone marrow examinations are helpful for
      diagnosis in time.

PMID- 18072627
TI  - [Retrospective analysis of 54 patients with high risk aggressive T-cell non
      Hodgkin lymphomas].
AB  - OBJECTIVE: To analyse the clinical characteristics, treatments and prognosis of
      patients with T-cell non-Hodgkins lymphoma (NHL) in intermediate-high and high
      risk. METHODS: Fifty-four patients with T-cell NHL classified intermediate-high
      and high risk were retrospectively analyzed. RESULTS: According to WHO
      classification criteria, there were 12 cases of T-lymphoblastic lymphoma (TLBL),
      31 peripheral T-cell lymphoma unspecified (PTCL-U), and 11 hepatosplenic T-cell
      lymphoma (HSTCL). The IPI were 12 cases of intermediate-high risk and 42 high
      risk. Of them, 49 cases were bone marrow affected and 7 CNS affected. The
      response rate (RR) for the whole group was 86.5%, complete remission (CR) rate
      67.3%, and 3-year survival rate 16.0%. The 3-year survival rates for
      haematopoietic stem cell transplantation and chemotherapy groups were 44.4% and
      8.3%, respectively. Multi-factor analysis showed that choice of therapy modality,
      and achievement of remission were significant factors for overall survival.
      CONCLUSION: T-NHL is a group of heterogeneous malignancies. The response rate of
      intermediate-high and high risk T- NHL, especially PTCL-U and LTBL, is not low,
      but its long-term outcome is poor. New treatment modality needs to be explored
      for these patients, and autologous HSCT is perhaps a good choice.

PMID- 18072628
TI  - [Multiplex fluorescence in situ hybridization for detecting complex chromosomal
      aberrations in chronic myeloid leukemia in blast crisis].
AB  - OBJECTIVE: To investigate the value of multiplex fluorescence in situ
      hybridization (M-FISH) for the detection of complex chromosomal abnormalities
      (CCA) of chronic myeloid leukemia in blast crisis (CML-BC). METHODS: M-FISH was
      used to study 26 cases of CML-BC with CCA assayed by conventional cytogenetics
      (CC). RESULTS: Sixty-nine kinds of structural rearrangements were detected by M
      FISH besides typical t (9;22) translocation, among them only 10 were balanced
      ones and 59 unbalanced ones including 1 insertion, 6 deletions, 52 translocations
      and derivative chromosomes. In addition, 23 numerical abnormalities were
      detected. All chromosomes were involved in CML-BC, and chromosomes 17, 2, 8, 16
      involvements were the most frequent. M-FISH failed to find out the abnormal clone
      in 1 case, discovered CCA clones that were missed CC in 6 cases. Clarified 16
      kinds of aberrations which could not be identified CC and corrected 5 aberrations
      made wrong description by CC. Thirty-five kinds of translocations were found by M
      FISH which were missed by CC. The aberrations of der (9) t (16; 6; 9; 22) and der
      (18) t (16; 18; 19) we found were reported in the literature for the first time.
      CONCLUSIONS: M-FISH can refine CCA in CML-BC, find out or correct the missed or
      misidentified abnormalities by CC. The frequent secondary chromosomal
      abnormalities in CML-BC with CCA are different from that in CML.

PMID- 18072629
TI  - [Development of Sweet syndrome in an acute promyelocyte leukemia patient during
      treatment with all-trans retinoic acid--case report and literature review].
AB  - OBJECTIVE: To identify the side effect of all-trans retinoic acid (ATRA), and
      improve early therapeutic response in patients with acute promyelocytic leukemia
      (APL). METHOD: The first case of Sweet's syndrome (SS) developed in a APL patient
      treated with ATRA was reported in mainland of China, and reviewed correlative
      literature. RESULTS: Only 14 cases of SS associated with ATRA therapy in APL have
      been reported in the literature, including the present case. The median age was
      49.5 years (9 -84) and 10 were women and 4 men. Of them, SS was restricted to the
      skin in 10 case, the other 4 muscle, fascia, kidney, and lung were involved. SS
      appeared after a median of 18 days of ATRA therapy (6 - 34 days). The median WBC
      count was 7.05 (0.80 - 23.00) x 10(9)/L. Four patients continued with the ATRA
      therapy without interruption, 13 patients treated with steroids and 12 responded.
      One patient improved without any treatment. Two cases of SS developed retinoic
      acid syndromes after ATRA therapy. CONCLUSION: Sweet's syndrome is a rare adverse
      effect of ATRA, and has similar features with inflammatory or infective
      dermatosis. The corticosteroids treatment could improve the systemic and
      cutaneous symptoms. When ATRA therapy was restarted after SS subsided, no
      recurrence of rashes was observed.

PMID- 18072630
TI  - [Role of Bid protein in the mitochondria and Endoplasmic Reticulum associated
      apoptotic pathway].
AB  - OBJECTIVE: To explore the role of Bid protein in the mitochondria and endoplasmic
      reticulum (ER) associated apoptotic pathway. METHODS: Apoptosis of MUTZ-1 cells
      induced by homoharringtonine (HHT) was measured by FACS. Mitochondria and ER
      associated apoptotic pathway was detected by RT-PCR and Western blotting. And the
      translocation of Bid protein was measured by laser scanning confocal microscope
      (LSCM). RESULTS: After exposure of MUTZ-1 to HHT at 0.05 microg/ml for 24 h,
      typical ER-stress phenomenon induced apoptotic cells and release of Ca2+ from the
      cytosolic Ca2+ storage and the loss of mitochondrial membrane potential were
      observed. RT-PCR analysis revealed that mRNAs for ER stress-associated
      proapoptotic factor were markedly increased at 4 h after 0.05 microg/ml HHT
      treatment and peaked at 12 h, then decreased steady. Activation of caspase
      protein was also observed at 8 h. The translocation of Bid protein from ER to
      mitochondria was observed at 12 h after HHT treatment. CONCLUSION: HHT can induce
      MUTZ-1 cells apoptosis. The cell death may be likely mediated by the ER stress
      pathway as well as mitochondrial pathway and Bid protein may be the cross talk of
      the two apoptotic pathways.

PMID- 18072631
TI  - [The correlation study of PTEN gene expression and Akt phosphorylation in
      myelodysplastic syndrome].
AB  - OBJECTIVE: To investigate the relationship between PTEN gene expression and Akt
      phosphorylation (p-Akt) in myelodysplastic syndrome (MDS) and to explore the
      progression of MDS and the mechanism of high risk transformation to acute myeloid
      leukemia. METHODS: RT-PCR was used to detect the PTEN mRNA expression in leukemia
      cell lines K562 (as negative control) and Jurkat (as positive control) and 65 MDS
      and MDS/AML patients. Flow cytometry was used to detect p-Akt in HL-60 and Jurkat
      cells and 30 MDS patients. RESULTS: (1) K562 cells present PTEN gene expression
      while Jurkat cells did not. Of 65 MDS and MDS/AML patients, 27 (41.5%) expressed
      PTEN mRNA, being significantly lower than that in normal group (85.7%) (P <
      0.01). (2) Jurkat cell showed high expression (86.9%) of p-Akt, while HL-60 cell
      as negative control did not express. P-Akt levels of 30 MDS patients were
      increased (1.35% - 58.23%), being much higher as compared with that of the normal
      contrast group (0.54% - 2.34%) (P < 0.01). Moreover, with the rate of blast cells
      increasing, the p-Akt level was rising up. There is a positive correlation (r =
      0.93, P < 0.01) between the low expression rate of PTEN and the positive rate of
      p-Akt. CONCLUSION: The loss of PTEN gene expression is one of the important
      factors of p-Akt high expression in MDS patients, moreover, it may speed up the
      progress of the MDS or transformation to acute myeloid leukemia.

PMID- 18072632
TI  - [The quantity, subsets and expression of costimulatory molecules of circulating
      dendritic cells in the patients with myelodysplastic syndromes].
AB  - OBJECTIVE: To investigate the quantity, subset of dendritic cells (DC) and their
      costimulatory molecule expression in peripheral blood (PB) of the patients with
      myelodysplastic syndromes (MDS). METHODS: Total DC (Lin1(+) HLA-DR(+)), myeloid
      DC (mDC) (Lin1(-) HLA-DR(+) CD11c(+)) and plasma DC (pDC) (Lin1(-) HLA-DR(+)
      CD123(+)) in fresh PB samples of 38 MDS patients and 19 normal controls were
      assayed by flow cytometry with the monoclonal antibodies. The expressions of
      costimulatory molecules CD80, CD86 and CD40 on these DCs were also assayed in the
      same way. RESULTS: The number of total DC in PB of low-risk and high-risk MDS
      patients was significantly higher than that in normal controls [(33.7 +/- 7.0) x
      10(6)/L, (56.3 +/- 29.0) x 10(6)/L vs (12.1 +/- 1.4) x 10(6)/L, respectively] (P
      < 0.05), that of mDC in PB of low-risk and high-risk MDS patients was higher than
      that of normal controls too [(16.7 +/- 6.3) x 10(6)/L, (28.7 +/- 17.6) x 10(6)/L
      vs (5.5 +/- 0.9) x 10(6)/L] (P < 0.05), but pDC in low-risk and high-risk MDS
      patients was not significantly higher than that in normal controls (P > 0.05).
      The percentage of total DC in PB mononuclear cells (PBMNC) of low-risk and high
      risk MDS patients [(2.37 +/- 0.53)% and (3.58 +/- 1.39)% respectively and that of
      mDC (0.90 +/- 0.35)%, (1.51 +/- 0.70)% respectively] were higher than that of
      normal controls [(0.68 +/- 0.08)%, and (0.32 +/- 0.05)% respectively] (P < 0.05),
      but that of pDC in MDS cases was not higher than that of normal controls (P >
      0.05). The expressions of CD80 and CD86 between MDS patients and normal controls
      had significant difference (P < 0.05). CONCLUSIONS: Total DC and mDC were
      increased significantly in MDS, but pDC did not. The costimulatory molecules
      (CD80 and CD86) except CD40 expressed higher on the DC of MDS patients. It
      suggested that the inflammatory injury related APC increased in MDS, but the
      antitumour immunity related APC did not . What found here might be one of the
      mechanisms involved in the pathogenesis of MDS.

PMID- 18072634
TI  - Shisha smoking--an imminent health hazard.

PMID- 18072633
TI  - [Preliminary study of biological characteristics of myelodysplastic syndromes
      clonal cells].
AB  - OBJECTIVE: To investigate the biological difference of clonal cells between
      myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). METHOD: Bone
      marrow (BM) clonal cells (which had cytogenetic markers detected by FISH assay)
      and blasts were quantitatively analysed in 51 MDS and 11 AML patients. The clonal
      cell percentage in orthochromatic normoblasts, granulocytes and megakaryocytes
      were assayed. The biological functions for phagocytosis and oxidation of MDS
      peripheral blood (PB) neutrophils were compared with that of normal controls.
      RESULTS: Almost all MDS patients BM had a higher clonal cell percentage (mean
      48.2%) than blasts percentage (mean 6.7%) (P < 0.01), but with the subtype of MDS
      advancing this percentage gap was closing up, and in 11 AML patients no such gap
      was observed. This gap in MDS patients with + 8 abnormality was smaller than in
      those with 5q -. In MDS BM, clonal cells were detected in segmented granulocytes
      (mean 45.9%), orthochromatic normoblasts (mean 46.0%) and mature megakaryocytes
      (mean 38.0%). In Addition, an approximate amount of clonal cells with the same
      karyotype abnormality in BM were detected in MDS PB (mean 37.3% in blood vs 48.6%
      in marrow). Functional analysis showed that the neutrophils in MDS PB could exert
      nearly normal physiological functions (P > 0.05), but those from AML could not as
      compared to healthy donors (P < 0.01). CONCLUSION: There is a significant
      difference in the biological features between MDS and AML clonal cells.

PMID- 18072635
TI  - Frequency of raised serum IgE level in childhood atopic dermatitis.
AB  - OBJECTIVE: To see the frequency of raised serum IgE level in children with atopic
      dermatitis. METHODS: The study was conducted in the out patient department of
      Dermatology, "Ziauddin University", KDLB Campus Karachi, from 1st October 2005,
      till 30th September 2006. Patients belonging to both sexes, aged upto 15 years,
      clinically diagnosed as atopic dermatitis were enrolled. The clinical severity
      was graded as mild, moderate and severe forms. Sera of all these patients were
      tested for IgE levels by ELISA. RESULTS: The study comprised of 124 patients,
      including 73 males (59%) and 51 females (41%). A total of 86 patients (70%) had a
      raised serum IgE level from a cut off value of 87 IU/ml. A large number of
      patients suffered from moderate disease (47%), followed by mild form (33%) and
      severe disease (20%). Serum IgE levels were divided into 3 groups i.e. upto cut
      off value (87 IU/ml) accounting for 31%, followed by 88 to 1000 IU/ml (41%) and
      1001 to 3000 IU/ml (28%). Of the severely affected 25 patients (20%), 20 (57%)
      had values ranging from 1001 to 3000 IU/ml while another 3 (6%) ranged less then
      1000 IU/ml (P < 0.001). Of those with moderate disease (47%), 13 patients (37%)
      had serum IgE levels ranging from 1001 to 3000 IU/ml, while 25 (49%) had levels
      less then 1000 IU/ml (P = 0.24). Of those affected mildly (33%), 23 (45%) had
      values ranging from 88 upto 1000 IU/ml and 2 patients (6%) had levels from 1001
      to 3000 IU/ml (P < 0.001). CONCLUSION: Majority of children suffering from atopic
      dermatitis have a raised serum level of IgE, which in turn correlates well with
      severity of the disease.

PMID- 18072636
TI  - Management of acute myeloid leukaemia--5 years experience at Armed Forces Bone
      Marrow Transplant Centre, Rawalpindi.
AB  - OBJECTIVE: To evaluate the outcome in denovo AML patients treated with different
      remission induction and consolidation chemotherapy regimens in our population.
      METHODS: A retrospective study on acute myeloid leukaemia (AML) patients was
      carried out at Armed Forces Bone Marrow Transplant Centre Rawalpindi Pakistan
      between July 2001 and June 2006. During 5 years period 46 patients received
      treatment for AML at our centre. Twenty nine patients were males and 17 were
      females. Median age of patients was 21 years (range: 7-56 years). These 46
      patients were categorized into two groups on the basis of type of leukaemia and
      chemotherapy given. In group-I 40 patients (group Ia: 23 patients of M1-M6, less
      M3 group Ib: 17 patients of AML M3) received anthracycline and cytarabin based
      chemotherapy. In group-II, six patients (AML- M3) received all trans retinoic
      acid (ATRA) based chemotherapy. RESULTS: In group Ia, out of 23 patients, 14
      patients (60.8%) achieved complete remission (CR) after remission induction
      chemotherapy, 10 patients remained in CR after 3rd and 4th consolidation. Eleven
      patients died and five patients relapsed during treatment and follow up. In this
      group overall CR, relapse rate (RR) and mortality was 30.4% (7/23), 21.7% (5/23)
      & 48% (11/23) respectively. In group Ib out of 17 patients, 9 patients (53%)
      achieved CR after remission induction. Eleven patients died during treatment
      while one patient relapsed in this group. Overall CR, RR & mortality was 29.4%
      (5/17), 6% (1/17) & 55% (11/17) respectively. In group II all patients achieved
      CR (100%) after 1st course of chemotherapy. Two of these patients unfortunately
      died of uncontrolled sepsis during 1st consolidation, while remaining 4 patients
      66.6% are on maintenance chemotherapy and are still in CR. CONCLUSION: Overall
      CR, RR and mortality in all groups was 35% (16/46), 13% (6/46) and 52% (24/46)
      respectively at a median follow-up of 36 + 8 months. Survival in AML-M3 patients
      treated with ATRA based chemotherapy is significantly superior than anthracycline
      based chemotherapy (66.6% vs. 29.4%). Infection and chemotherapy toxicity being
      major causes of mortality.

PMID- 18072637
TI  - Treatment of ureteric calculi--use of Holmium: YAG laser lithotripsy versus
      pneumatic lithoclast.
AB  - OBJECTIVE: To compare the efficacy of Holmium: YAG laser and pneumatic lithoclast
      in treating ureteric calculi. METHODS: The study included total of 100 patients
      divided into two equal groups of laser lithotripsy (LL) and pneumatic lithoclast
      (PL). Study was conducted between September 2006 and February 2007. Inclusion
      criteria were patients with a ureteric stone of size 1-2 cm and negative urine
      culture. An x-ray KUB was mandatory. IVU and CT pyelogram were also done when
      required. Procedures were done under general anaesthesia after a single dose of
      pre-operative antibiotic. A 7.5 Fr semi rigid ureteroscope was used for
      ureteroscopy in all cases. Holmium: YAG laser with 365 microm wide probe was
      employed in laser group and frequency was set between 5 and 10 Hz at a power of
      10 to 15 W. Swiss lithoclast with single or multiple fire technique was used
      accordingly in PL group. Postoperatively patients underwent radiography and
      helical CT as required at 4th week of follow up to asses stone clearance.
      RESULTS: The mean patient age in LL and PL group was 38 +/- 10 and 40 +/- 10
      years respectively. The male to female ratio and stone size were similar between
      the groups. Stone migration up in pelvicalyceal system occurred in two patients
      of LL group while in eight patients of PL group. JJ Stent was placed in 5(10%)
      patients in laser group where as 13 (26%) patients required it in pneumatic
      lithoclast group. Stone free rate at 4 weeks was 92% in laser group as compared
      to 82% in pneumatic lithoclast group. Hospital stay was more than 24 hours in 2
      patients of laser group as compared to 5 patients of pneumatic lithoclast group.
      Complication rate was 4% in LL group whereas it was 14% in PL group. CONCLUSION:
      Holmium: YAG laser lithotripsy is a superior technology compared to pneumatic
      lithoclast in terms of rate of stone clearance and complications, especially in
      upper ureteric stones.

PMID- 18072638
TI  - Accurate record keeping in referral hospitals in Pakistan's north west frontier
      province and Punjab: a crucial step needed to improve maternal health.
AB  - OBJECTIVE: To assess record keeping practices in referral hospitals in the North
      West Frontier Province (NWFP) and Punjab province, focusing specifically on
      United Nation's Emergency Obstetric Care (UN EmOC) indicators of maternal
      morbidity and mortality. METHODS: This cross-sectional survey collected
      information at the health facility level, using UN process indicators to assess
      EmOC services. The study enrolled 170 health facilities from 19 randomly selected
      districts in Punjab and NWFP. RESULTS: The study found poor record keeping
      practices in the health care facilities of both provinces. A few facilities had
      no records at all; information on obstetric complications was inconsistent. Many
      facilities' records were marked by duplications, inaccuracies, and data was
      deficient. CONCLUSION: Health policies and planning in any country depend heavily
      on having correct and timely information on health parameters. In Pakistan, many
      recording and data collection problems can be solved by having well-designed and
      accurately maintained data registers. Proper and regular supervision and staff
      training are invaluable components of data collection. Efforts to improve record
      keeping may provide a low-cost, low-technology way to document progress towards
      improving maternal health.

PMID- 18072639
TI  - Arterial to end-tidal carbon dioxide difference in neurosurgical patients
      undergoing craniotomy: a review of practice.
AB  - OBJECTIVE: To see if PETCO2 reflects PaCO2 with acceptable accuracy. METHODS: In
      this audit the.anaesthetic chart of fifty consecutive patients, age 12 years and
      above undergoing craniotomy for intracranial pathology, were reviewed. RESULTS:
      The difference between end tidal carbon dioxide (ETCO2) value corresponding to
      the time of taking the arterial sample and the PaCO2 was calculated. The mean end
      tidal CO2 was 29.3 +/- 2.8 and the mean PaCO2 was 32.63 +/- 4.5. The mean
      difference between the two values was calculated as 4.09 +/- 3.0. The regression
      coefficient was 0.496, which showed a moderate association. A wide variability
      was observed in the results. CONCLUSION: Based on our results we recommend that
      arterial samples should be taken to determine PaCO2 in neurosurgical patients
      where maintenance of cerebral blood flow is crucial e.g. cerebral aneurysm
      surgery

PMID- 18072640
TI  - Safety of cytotoxic chemotherapy during pregnancy.
AB  - OBJECTIVE: To To present an experience and results of treatment of pregnant
      cancer patients with cytotoxic chemotherapy from second trimester of pregnancy.
      METHODS: Eighteen consecutive pregnant patients treated at Khyber Teaching
      Hospital, Peshawar between December 2000 and August 2006 for different types of
      malignancies are reported. Six patients (33%) had breast cancer, four (22%) had
      chronic myeloid leukaemia, two (11%) had Hodgkin's disease, two (11%) had acute
      myeloid leukaemia and one each had recurrent ovarian carcinoma (5.7%), soft
      tissue sarcoma (5.7%), acute lymphoblastic leukaemia (5.7%) and non-Hodgkin's
      lymphoma (5.7%). Various chemotherapeutic protocols were administered from second
      trimester of pregnancy onwards. Detailed obstetrical examinations and high risk
      foetal ultrasound monitoring were performed regularly. RESULTS: Two patients were
      lost to follow-up after one course of chemotherapy while two patients chose to
      have therapeutic abortion. Out of the remaining 14 patients, one patient had
      spontaneous abortion while one patient had an intra-uterine death of foetus
      during chemotherapy. Remaining 12/14 (86%) patients gave birth to live, healthy
      babies and no foetal malformations were observed. Six out of 140 breast cancer
      patients (4.3%) during the study period had concomitant pregnancy. Four patients
      with breast cancer had modified radical mastectomy with axillary dissection
      during pregnancy (median gestational age 22 weeks) and no operative or post
      operative complications were noted. Three out of four breast cancer patients
      (75%) had hormone receptor negative tumours. CONCLUSION: Chemotherapy during the
      second and third trimester of pregnancy can be safe if proper obstetric and
      radiologic monitoring is performed. Long term side-effects in these children need
      to be studied with extended periods of follow-up.

PMID- 18072641
TI  - Psychiatry in Pakistan: 1947-2006: a new balance sheet.
AB  - This review deals with the evolution of psychiatry in Pakistan since its
      inception in 1947. It describes the situation of psychiatric services, education
      and research through the years 1947-2006, presenting a picture of existing mental
      health scenario, suggesting the ways for improvement and comment on possible
      future developments. It concludes with the prediction of a revolutionary change
      in the current shape of psychiatry throughout the world and especially in
      Pakistan whereby psychiatry will change to organic-based discipline of a wider
      "Neurosciences".

PMID- 18072642
TI  - Severe anaphylactic reaction at induction of anaesthesia.
AB  - Anaphylaxis is an IgE mediated severe allergic reaction causing release of
      vasoactive substances from mast cells and basophils after re-exposure to an
      antigen. Signs and symptoms include flushing, urticaria, hypotension,
      tachycardia, bronchospasm, cardio-respiratory arrest etc. It can occur at
      induction of anaesthesia when multiple drugs are being administered, but prompt
      diagnosis with correct management is the key to a successful outcome. This case
      report describes a patient who developed severe bronchospasm with difficulty in
      inflating the lungs and dropping oxygen saturations, alongwith hypotension,
      tachycardia and widespread flushing, at induction of anaesthesia for elective
      breast surgery. She was promptly managed and her hypotension was corrected, but
      the bronchospasm was more resistant to treatment. The patient also developed ST
      segment elevation, which was successfully managed with intravenous
      glyceryltrinitrate. The bronchospasm responded slowly to salbutamol and
      aminophylline. The patient underwent surgery and was discharged home on the third
      postoperative day.

PMID- 18072643
TI  - Subcutaneous facial mycosis in a child due to Madurella mycetomatis.
AB  - Mycetoma is a chronic, granulomatous, subcutaneous, inflammatory disease caused
      by true fungi (eumycetoma) or filamentous bacteria (actinomycetoma). Eumycetoma
      usually affects adult males involving limbs and other exposed body parts.
      Children represent the least commonly encountered age group with this disease. A
      case of subcutaneous facial mycosis due to Madurella mycetomatis in a three year
      old child was diagnosed at the Microbiology department Armed Forces Institute of
      Pathology Rawalpindi, which to our knowledge is the first case reported of its
      kind. Early diagnosis and timely medical therapy lead to favourable outcome
      without any surgical intervention.

PMID- 18072644
TI  - Posterior reversible leukoencephalopathy.
AB  - Posterior Leukoencephalopathy is a rare, though reversible complication of
      eclampsia. We report two cases, in which patients with eclampsia presented with
      seizures, visual disturbances and focal neurological signs with high intensity
      areas predominantly in parieto-occipital white matter on cranial MRI, where
      successful control of blood pressures led to complete resolution of neurological
      deficits as well as radiological abnormalities. It is an infrequently recognized
      neurological disorder, not known to many physicians, which has almost complete
      recovery with early diagnosis and treatment. The purpose of presenting this case
      series is to highlight the importance of early recognition and treatment of this
      potentially reversible disorder.

PMID- 18072645
TI  - Role of Stellate ganglion block in post CABG sympathetically mediated chest pain.
AB  - Acute chest pain is a common presentation in emergency. After clinical assessment
      undiagnosed chest pain can become a difficult problem. Sympathetically mediated
      chest pain is a rare presentation, as it is similar to that of secondary
      hyperalgesia in the intact skin surrounding an injury site. We are reporting a
      case of a 62 years old man who presented with atypical chest pain four months
      after coronary artery bypass grafting (CABG). On investigation no new change was
      noticed than previous evaluation. On chronic pain assessment he was having
      hyperalgesia to light touch in addition to the spontaneous chest pain. He was
      treated as a case of sympathetically mediated chest pain, pain modulators,
      analgesics and Stellate ganglion block. Patient responded dramatically to
      Stellate ganglion block and returned to work within two weeks time. This case
      illustrated the importance of early diagnosis of sympathetically mediated chest
      pain and role of Stellate ganglion block.

PMID- 18072646
TI  - A structured and standardized national postgraduate medical trading policy: need
      of the time.

PMID- 18072647
TI  - Spontaneous infectious spondylodiscitis [corrected] (SIS) or pseudo-Pott's
      disease.

PMID- 18072648
TI  - Utility of MRI in assessment of pituitary iron overload.
AB  - Beta thalassemia is highly prevalent in Pakistan with a carrier rate of 5-8%. The
      main complication of beta thalassemia major is iron overload, especially in
      reticuloendothelial system, heart, joints and endocrine glands. Pituitary
      siderosis leads to hypogonadotropic hypogonadism and growth hormone deficiency.
      Measures of plasma ferritin levels and hepatic iron level are used for assessing
      body iron overload but these are limited for various reasons particularly in case
      of pituitary siderosis. Magnetic Resonance Imaging (MRI) is a reliable, non
      invasive and easily available utility for assessing tissue siderosis. We assessed
      a 20 year old female beta thalassemic diagnosed with hypogonadotropic
      hypogonadism and pituitary siderosis using routine spin echo (SE) T1 and T2
      weighted sequences of MRI and special Gradient Recalled Echo (GRE) sequence of
      MRI. We found MRI signal intensity to be decreased on all three sequences but
      most so on GRE suggesting its greatest sensitivity to pituitary iron deposition.
      MRI signal hypo-intensity due to paramagnetic effects of iron has been validated
      for liver siderosis but is still under investigation for pituitary siderosis. Our
      findings suggest that MRI especially GRE sequence can be used in conjunction with
      laboratory data to evaluate pituitary siderosis and to prevent further pituitary
      dysfunction.

PMID- 18072649
TI  - [Vascular dysfunction in metabolic disorders: evaluation of some therapeutic
      interventions].
AB  - Cardiovascular diseases continue to be the main cause of death in most
      industrialized countries. Endothelial dysfunction, a systemic process, is the
      earliest known marker of atherosclerosis and has become a major focus in acute
      ischemic disorders. We are investigating the hypothesis that, in these diseases,
      microvascular and endothelial dysfunctions occur simultaneously and precede the
      onset of macrovascular disease. We studied, to our knowledge for the first time
      in the same subjects, microvascular and endothelial functions in 11 patients with
      type 2 diabetes. 36 metabolic syndrome patients (NCEP-ATPIII criteria) and 25
      young obese women matched with healthy controls. Micro vascular morphology and
      hemodynamics were evaluated non-invasively by means of nailfold
      videocapillaroscopy. Red blood cell velocity (RBCV, mm/s) was measured at rest
      and after release from 60 s of arterial occlusion (RBCVmax, mm/s) at the finger
      base, along with the time to reach RBCVmax (TRBCVmax, s), by video analysis with
      Cap Image software. Venous occlusion plethysmography was performed after intra
      arterial infusions of acetylcholine and sodium nitroprusside to assess endo
      thelial-dependent and -independent vasodilation, respectively. We found similar
      results in the three groups of subjects, namely a significant decrease in
      RBCVmax, an increase in TRBCVmax, and a decrease in endothelial-dependent
      vasodilation. These findings clearly demonstrate that the two dysfunctions occur
      simultaneously in these groups of patients. Several mechanisms which could impair
      micro vascular and endothelial functions are associated with insulin resistance,
      and drugs that act on insulin resistance might thus be beneficial. Metformin,
      given to 16 first-degree relatives of patients with type 2 diabetes mellitus, who
      had the metabolic syndrome and normal glucose tolerance (ADA criteria), improved
      endothelial-dependent vasodilation and microcirculatory function. Rosiglitazone,
      given to 18 patients with the metabolic syndrome, enhanced vascular responses by
      improving endothelial function and increasing adiponectin levels. Increased
      triglyceride storage is often associated with insulin resistance, contributing to
      free fatty acid (FFA) overexposure. The two drugs tested here stimulate AMP
      activated protein kinase, which promotes FFA oxidation and thus reduces oxidative
      stress, and might therefore attenuate endothelial lipotoxicity. The results
      strongly suggest that targeting micro vascular and endothelial dysfunctions in
      patients with metabolic disorders might help to prevent cardiovascular events,
      and warrant long-term clinical trials.

PMID- 18072650
TI  - [Whole-body ultrasound in the ICU. A visual approach to the critically ill].
AB  - Sonography is a non invasive method allowing prompt diagnosis at the bedside,
      especially when sophisticated diagnostic tools are unavailable, as in the
      critical care setting. In particular, the lung, a vital organ, is fully
      accessible, and the signs are simple and standardized. Accurate diagnosis is
      possible in extreme emergencies, as in patients with pleural effusion, alveolar
      consolidation, interstitial syndrome or pneumothorax. The clinical relevance of
      these diagnoses, and especially the interstitial syndrome, is discussed.
      Sonography also allows cost savings and avoids unnecessary irradiation.

PMID- 18072651
TI  - [Vascular complications of essential thrombocythemia].
AB  - Vascular manifestations are the main clinical complication of essential
      thrombocythemia (ET). They include arterial thrombosis (30-40% of patients),
      venous thrombosis (5%), and ischemia due to microcirculatory disorders. Their
      incidence is highest at disease onset and diminishes gradually thereafter. The
      pathophysiology of ET involves dysmegakaryocytopoiesis, leading to platelet,
      leukocyte and vascular endothelial cell activation. The recent discovery of the
      V617F mutation of the JAK2 tyrosine kinase in 50-60% of patients with ET defined
      a new subgroup resembling polycythemia vera. This review examines biological
      findings and their correlation with the risk of thrombosis. Until now,
      stratification of the vascular risk has relied on a clinical case-control study
      showing that thrombotic and vascular complications are more frequent in patients
      over 60 and those with a history of thrombosis. These criteria, along with a
      rapid increase in thrombocytosis (>1500 G/L) leading to an increase in the
      bleeding risk, define a high-vascular-risk subgroup of patients warranting
      cytoreductive therapy. Although many biological markers of
      dysmegakaryocytopoiesis and cellular hyperactivation have been linked to an
      increase in the thrombotic risk, none is available for large-scale prediction of
      an intermediate vascular risk. The role of the JAK2 V617F mutation itself is
      controversial. Whatever the ET subgroup, antiplatelet therapy is largely used,
      based on the results of the ECLAP prospective controlled trial that showed a
      statistically significant reduction in thrombotic complications in patients
      receiving aspirin for polycythemia vera, a very similar myeloproliferative
      disorder.

PMID- 18072652
TI  - [Essential thrombocythemia. Contribution of the V617F JAK2 mutation to the
      pathophysiology, diagnosis and outcome].
AB  - An increased platelet number in blood depends on a limited spectrum of causes,
      which aren't always simple to identify. Secondary thrombocytosis is a reactive
      process in relation with acute or chronic inflammatory diseases, or asplenia. The
      infrequent inherited thrombocytoses disorders are suspected when similar cases
      are observed in the same family. However, the most frequent causes of chronic
      thrombocytosis in adults are the so-called chronic myeloproliferative syndromes
      (chronic myelocytic leukaemia, polycythemia vera, primary myelofibrosis,
      essential thrombocytemia), and to a lesser extent, myelodysplastic syndromes. In
      the course of these disorders, thrombocytosis is often the first recognized
      abnormality. Chronic myelocytic leukaemia is easily diagnosed owing to the
      presence of either the Philadelphia chromosome or the BCR-ABL fusion gene
      product. The next step still relies upon a distinction according to the PVSG or
      the WHO criteria of Polycythemia Vera (PV) and Idiopathic myelo fibrosis (IMF) to
      finally confirm genuine Essential Thrombocythemia (ET). The recent description of
      the V617F mutation of JAK2 in 90% of PV patients, 43 to 67% with IMF and 50% of
      ET diagnosed according to either the PVSG or the WHO criteria is a definite
      characteristic of clonality now accessible in haematology practice. However, this
      mutation is neither specific nor constant in any of the Philadelphia negative
      myeloproliferative disorders, which outlines the importance of the WHO criteria
      of megakaryocytic abnormalities on bone marrow biopsy as the hallmark of Ph
      negative MPDs. The exclusion of PV and of IMF, including pre fibrotic and early
      fibrotic forms is still required for the diagnosis of "true" ET. Disease
      stratification and treatment strategy are targeted on the evaluation and
      prevention of vascular complications. Acute leukaemia or myelodysplasia, and
      other clonal progressions like myelofibrotic transformation, are infrequent and
      delayed events. However, according to the present data, the risk of fibrotic
      progression or of leukaemic transformation is not related to the mutation status
      of ET patients.

PMID- 18072653
TI  - [Renal and aortic involvement in Takayasu's disease].
AB  - From 1972 to 2003, we surgically treated 25 patients (17 females) for aortic and
      renal complications of Takayasu's disease. Their mean age was 18.5 +/- 11.2
      years. Despite heavy medical treatment, all had severe uncontrollable
      hypertension. Nineteen patients had associated lesions of the aorta and renal
      arteries, 6 had isolated lesions of a renal artery, and 10 had lesions of the
      mesenteric arteries. Percutaneous transluminal angioplasty of the renal artery or
      arteries was attempted in four cases and was always unsuccessful. Thirteen
      patients with bilateral lesions underwent nephrectomy (three cases) and renal
      artery repair (35 cases). Aortic bypass was performed in 7 patients and
      revascularization of other visceral arteries in 4 patients. Follow-up ranges from
      1 to 20 years (mean 5 years). There were no deaths. Three thromboses occurred
      post-operatively, two in a renal artery and one in the superior mesenteric
      artery. Immediately after the operation blood pressure normalized in 18 patients
      (72%), was improved in 4 (16%) and remained unchanged in 3 (12%). The disease
      progressed in 11 patients (44%), with four recurrent stenoses of renal arteries,
      3 aggravations of aortic lesions (requiring an aortic bypass in one patient at
      three years), 3 aggravations of supraaortic artery involvement, and one case of
      coronary insufficiency requiring bypass at 8.5 years. Long term blood pressure
      normalized in 14 patients (56%), was improved in 5 patients (20%) and remained
      unchanged in 6 patients (24%), owing mainly to secondary or late anatomical
      deterioration.

PMID- 18072654
TI  - [Renal transplantation in children with lower urinary tract dysfunction].
AB  - Lower urinary tract dysfunction can lead to renal failure, owing to chronic
      infection and hypertension resulting from incomplete bladder drainage. These
      complications can recur after grafting. We compared the outcome of renal
      transplantation between patients with lower urinary tract dysfunction (group A)
      and upper urinary tract dysfunction (group B). One hundred twenty-seven kidney
      transplants were performed in 118 children in our institution between November
      1988 and October 2005. Thirty-four patients had urinary tract anomalies (17 in
      group A, 17 in group B). The disorders in group A included posterior urethral
      valves (11 cases), neurogenic bladder (4 cases), bladder extrophy (1 case), and
      the Prune-Belly syndrome (1 case). We reviewed infectious and surgical
      complications, patient and graft survival, and graft function based on serum
      creatinine levels at 1, 5 and 10 years. Statistical analysis was based on the
      Mann-Whitney test. In group A, 5 patients had augmented bladder, 2 had
      incontinent urinary conduit, and 1 was transplanted on a pre-existing cutaneous
      ureterostomy. In nine cases, transplantation was performed on the native bladder,
      with no preparation. Seven complications were noted in group A, consisting of
      recurrent pyelonephritis (2 cases), renal abscess (1 case), upper urinary tract
      dilation (3 cases), lithiasis (1 case) and urinary tract incrustation by
      Corynebacterium in the ureterocutaneous conduit (1 case). Three complications
      occurred in group B, consisting of acute pyelonephritis (2 cases) and urinary
      tract infection with prostatitis and epididymitis (1 case). Complications tended
      to be more frequent in group A, but the difference was not significant (p=0.246).
      Mean graft survival is 5.29 years in group A and 5.97 years in group B (p=0.76).
      There was no difference between the two groups as regards the serum creatinine
      level at 1 year (p=0.77 ; Mann-Whitney test), 5 years (p=0.81) or at the end of
      follow-up (p=0.75). These results suggest that renal transplantation is similarly
      feasible in children with upper and lower urinary tract dysfunction. Indeed, we
      found no significant difference between the groups in terms of patient survival
      or graft survival and function.

PMID- 18072655
TI  - [Clinical and benign aspects of human papillomavirus-associated lesions].
AB  - Human papillomaviruses (HPV) are found in most human epithelia and some tumors.
      Most HPV strains associated with cutaneous lesions belong to three types, named
      alpha, beta and gamma. Although the causal link between genital human
      papillomavirus infection and cervical neoplasia is well established, the role of
      beta-HPV in non melanoma skin cancers is unclear. HPV mainly causes benign
      cutaneous lesions on the hands and soles. Genital HPV infection is the most
      common sexually transmitted infection. It is generally asymptomatic. The genitals
      can be infected by two low-risk HPV types (6 and 11), which are responsible for
      benign anogenital warts (condylomata acuminata). The implications of anogenital
      warts in children are highly controversial as regards sexual abuse. Treatments
      (chemical, physical or immunological) are lengthy, expensive, inconvenient and
      often painful. Recurrence is frequent because of HPV persistence in perilesional
      skin.

PMID- 18072656
TI  - [Intraepithelial lesions and neoplasia associated with human papillomavirus
      infection].
AB  - Anogenital lesions induced by human papillomaviruses (HPV) are due to both high
      risk HPV types involved in carcinogenesis of the cervix (and also, to a lesser
      extent, of the vulva, anus and vagina) and to low-risk HPV types that cause
      external genital warts in the perianal region, perineum, vulva and vagina (less
      often the cervix). Cervical cancer is thus virus-induced, and there is a
      continuum from intraepithelial lesions to invasive cancer. This offers the
      opportunity to screen cervical smears for cytological abnormalities or to detect
      high-risk HPV infection by molecular methods. Although the causal link between
      human genital papillomavirus infection and cervical neoplasia is well
      established, the role of beta-HPV in non melanoma skin cancers is unclear.

PMID- 18072657
TI  - [Virological and carcinogenic aspects of HPV].
AB  - Human papillomaviruses are small viruses belonging to the Papillomaviridae. More
      than 100 genotypes have been identified, causing benign (low-risk HPV) or
      malignant (high-risk HPV) cutaneous or mucosal lesions. The low-risk HPV6 and
      HPV11 provoke genital warts, while the high-risk HPV16 and HPV18 can cause
      cervical cancer. The HPVgenome includes several open reading frames that encode
      proteins involved in viral DNA replication (E1 and E2), viral gene expression
      regulation (E2), virus assembly (E4) and the immortalisation and transformation
      of infected epithelial cells (E5, E6 and E7; high-risk HPV only). The open
      reading frames L1 and L2 encode the two capsid proteins. HPV target stem cells of
      the squamous epithelium. The complete life cycle involves three phases, with
      sequential expression of viral genes leading to viral DNA replication and to the
      production of highly infectious virions. Viral DNA integration occurs with high
      risk types and leads to the overexpression of two viral oncoproteins, E6 and E7.
      These proteins, in combination with E5, promote the immortalisation and
      transformation of infected cells.

PMID- 18072658
TI  - [Professor Joseph Grancher (1843-1907). 100th anniversary of the death of a
      convinced follower of Pasteur].

PMID- 18072659
TI  - How social work can influence hospital management of fatal illness.

PMID- 18072660
TI  - Zelda's life: attention must be paid.

PMID- 18072661
TI  - The development of palliative care programs in the Veterans Administration: Zelda
      Foster's legacy.
AB  - The U.S. Department of Veterans Affairs (VA) has been a leader in program
      development and service delivery in the areas of geriatrics, hospice and
      palliative care for decades. Zelda Foster, MSW, serving as the Chief of Social
      Work Services at the Brooklyn VA Hospital for almost 20 years, was a force in the
      early days of the palliative care and hospice movement in the United States,
      publishing a seminal article in 1965, and contributing through educational
      initiatives, program development, information dissemination and mentorship of
      countless social workers. With an early recognition of the demographic imperative
      of aging veterans, the VA established a number of innovative programs which have
      been widely replicated outside of the VA. Zelda Foster was a central figure in
      the evolution of these programs and a strong and effective advocate for the
      inclusion of social workers. She deserves much credit for the fact that social
      workers are now centrally involved in an array of leadership activities in
      palliative and end-of-life care both within and outside of VA.

PMID- 18072662
TI  - Zelda Foster: a social work mentor's legacy.

PMID- 18072663
TI  - Zelda Foster and her contributions to social work in end-of-life care.
AB  - This article is both a memoir of one social worker's professional collaboration
      with Zelda Foster and a tribute to Zelda's legacy in the form of an educational
      resource on end-of-life care. It reviews achievements of Zelda Foster in social
      work practice and teaching related to death and dying. Resources presented in
      this article were supported by the Soros Foundation's Project on Death in
      America, a funded grant project to which Zelda contributed. The end-of-life care
      education, training and informational tools discussed in this article are
      examples of ongoing efforts in the social work profession to improve the lives of
      the dying and bereaved.

PMID- 18072664
TI  - The fight to eradicate hunger and poverty.

PMID- 18072665
TI  - Poverty--what's your role?

PMID- 18072666
TI  - A mission of mercy.

PMID- 18072667
TI  - Antibiotic therapy for pulmonary exacerbations in adults with cystic fibrosis.
AB  - Individuals with CF are living longer but often with chronic lung infections.
      Effective antibiotic therapy is necessary to treat life-threatening infectious
      exacerbations. Knowledge of the particular requirements of antibiotic therapy for
      the patient with CF allows the nurse to anticipate management plans, prepare for
      inpatient and outpatient care, and assess response to treatment.

PMID- 18072668
TI  - Clinical assessment and management of psychiatric patients' violent and
      aggressive behaviors in general hospital.
AB  - Patients with co-morbid psychiatric disorders exhibiting violent and aggressive
      behaviors can be a challenge for nurses in medical-surgical units. They can
      deliver effective, safe care by assessing risk and building a rapport with the
      patient during the admission process; utilizing crisis prevention strategies,
      including appropriate medication administration, environmental, psychobiological,
      counseling, and health teaching interventions; and employing conflict resolution
      technique. Utilizing the nursing process, the nurse can provide effective
      therapeutic interventions to promote safety for both the patient and the nurse.

PMID- 18072669
TI  - Comparison of job satisfaction between experienced medical-surgical nurses and
      experienced critical care nurses.
AB  - Hospitals continue to experience high nurse turnover rates. Based on the need to
      retain skilled nurses, differences in job satisfaction of experienced medical
      surgical and critical care nurses were examined.

PMID- 18072670
TI  - Sociodemographic variables predicting poor post-discharge outcomes for
      hospitalized elders with heart failure.
AB  - Elders with heart failure are at high risk for poor postdischarge outcomes such
      as rehospitalizations, emergency department use, and unscheduled physician
      visits. This study was conducted to determine if sociodemographic characteristics
      would aid in identifying high-risk individuals.

PMID- 18072671
TI  - The medical-surgical nurse's guide to ovarian cancer: Part II.

PMID- 18072672
TI  - Update on pain management: new methods of opiate delivery.

PMID- 18072673
TI  - Immunization for older adults.

PMID- 18072674
TI  - Understanding benign prostatic hyperplasia (BPH).

PMID- 18072676
TI  - More POCT on CBG.

PMID- 18072675
TI  - Nursing and the art of stewardship.

PMID- 18072677
TI  - Solving the puzzle of laboratory preparedness: the National Response Plan.

PMID- 18072678
TI  - A New Orleans hospital weathers the storm.

PMID- 18072679
TI  - Metabolic syndrome: an up prevalence, criteria, and laboratory testing.

PMID- 18072680
TI  - One lab's path to a quality-management system.

PMID- 18072681
TI  - Robotics in the laboratory: where we have been and where we are going.

PMID- 18072682
TI  - The Dark Report's Robert Michel extrapolates industry trends.

PMID- 18072683
TI  - Get it in writing.

PMID- 18072684
TI  - Competitive bidding: where do clinical laboratories stand?

PMID- 18072685
TI  - How can we fight to protect our professionalism?

PMID- 18072686
TI  - Happy holidays? Hope and help for stressed-out doctors.

PMID- 18072687
TI  - Enough blame to go around.

PMID- 18072688
TI  - PHP: rescuing the wounded healer--pt. III.

PMID- 18072689
TI  - Udom undone: Tennessee enacts new law regarding physician non-compete agreements.

PMID- 18072691
TI  - Use of telemedicine supports doctor-patient interaction between office visits.

PMID- 18072690
TI  - Just click or call for medical library services.

PMID- 18072692
TI  - Emerging drug therapies for the management of acute decompensated heart failure.
AB  - The mortality and morbidity of patients with heart failure (HF) remains
      unacceptably high despite current advances in medical therapies. In recent years,
      rapid growth in understanding the pathophysiology of heart failure has allowed
      for insights into many potential new therapeutic strategies. Yet until now,
      despite sound biological basis for efficacy and success in early-phase studies,
      novel agents have not stood up to the scrutiny of late-phase clinical trials.
      This review will examine the key emerging therapies for acute decompensated heart
      failure (ADHF), in light of available pathophysiological and clinical evidence.
      Several new agents for ADHF use novel mechanisms of action that focus on new
      treatment targets, such as those providing anti-ischemic and anti-stunning
      effects, blocking vasopressin receptors, blocking endothelin-1 receptors, or
      endogenous cardiac neurohormones and B-type natriuretic peptide (BNP).

PMID- 18072693
TI  - Consequence of physician disruptive behavior.

PMID- 18072695
TI  - Predictors of good adherence of adolescents with diabetes (insulin-dependent
      diabetes mellitus).
AB  - OBJECTIVES: The purpose of this study was to identify the factors that predict
      good adherence to health regimens by adolescents with diabetes (insulin-dependent
      diabetes mellitus). METHODS: Altogether, 300 individuals aged 13-17 years were
      randomly selected from the Finnish Social Insurance Institution's register.
      Ninety-seven per cent (N=289) of the selected adolescents returned the
      questionnaire. The data were analysed using the SPSS (Statistical Package for
      Social Sciences) for Windows software package. Logistic regression was used to
      find the factors that predict good adherence to health regimens. RESULTS: About
      one-fifth (19%) of the respondents with diabetes felt that they complied fully
      with the health regimens, while 75% placed themselves in the category of
      satisfactory adherence, and the remaining 6% reported poor adherence. The most
      powerful predictor was the threat to mental wellbeing. The likelihood that
      adolescents who felt the disease to be a threat to their mental wellbeing would
      comply with health regimens was 7.68-fold as compared to those who did not regard
      the disease as a threat to their mental wellbeing. The next most powerful
      predictor was support from physician. The support from nurses, and the
      motivation, energy and willpower to take care of themselves and the threat to
      physical wellbeing, also predicted good adherence. The logistic regression model
      explained 82% of the variance, and the model predicted correctly 88% of the
      adolescents with good adherence. DISCUSSION: This paper shows that adolescents
      with diabetes show quite good adherence. It also indicates the factors that
      predict good adherence to health regimens. To improve adherence, these factors
      should be given special attention in the care of adolescents.

PMID- 18072694
TI  - Differences in the prevalence of metabolic syndrome in urban and rural India: a
      problem of urbanization.

PMID- 18072696
TI  - Understanding the diversity and dynamics of living with diabetes: a feasibility
      study focusing on the case.
AB  - Despite growing evidence about treatments, many people living with diabetes have
      poor diabetes control even when healthcare is available. One difficult issue is
      how to apply medical evidence to individuals. This feasibility study explores
      change over time and the diversity of pathways to similar health outcomes, to
      understand how evidence can be tailored to the individual. Six people living with
      diabetes (two with type 1, and four with type 2) agreed to a series of interviews
      and diary-keeping. Reading the dataset for each individual reveals a person
      changing over time through interactions with people and their context.
      Identifying time as a theme is difficult, as it is ubiquitous. Outcome means
      little to those living with diabetes: they are living on through time. We
      developed attributes for each participant relevant to diabetes outcome,
      describing how they related to others and their environment, capturing emergent
      properties rather than detail. A similar health outcome could be achieved very
      differently. Comparison of patterns of attributes may be useful. However, the
      dynamic, relational nature of the attributes is easily lost from view. How people
      function in terms of time, change and interaction may be most important for
      tailoring interventions for improved health outcome.

PMID- 18072697
TI  - Identifying the patient perspective of the quality of mental healthcare for
      common chronic problems: a qualitative study.
AB  - OBJECTIVES: To identify which aspects of quality are important to individual
      patients with common chronic mild-to-moderate mental health problems presenting
      to general practice and the best method of involving patients with chronic mental
      health problems in the research process, and to contrast the relevance of a
      generic questionnaire developed previously with these individual patient
      narratives. METHODS: Qualitative interviews with 16 patients in Chester and
      Manchester were subjected to thematic analysis. RESULTS: Six key themes were
      identified in relation to the individual patient experience set against a generic
      patient experience: (1) the healthcare system provides a generic 'one size fits
      all' service, which is incompatible with an individual patient's experience and
      sense of being as an individual and that privileges medical over social care; (2)
      patients with mild-to-moderate mental health problems often have feelings of
      powerlessness and of being 'lost' in a system that is more responsive to severe
      and acute episodes of illness than to chronic morbidity; (3) patients often have
      unmet needs in relation to the distress of living with mild-to-moderate mental
      health problems; (4) there are substantial quality deficits in primary care for
      people with mild-to-moderate chronic mental health problems; (5) general
      practitioners are rated highly, and the attributes of a good general practitioner
      can be identified; patients also value continuity of care; (6) engaging people
      with common chronic mental health problems in the research/policy process
      requires generic assessment of quality using questionnaires supplemented with
      more in-depth methods, such as interviews and focus groups. Interviewees
      highlighted substantial quality deficits in service provision for people with
      chronic mental health problems. Involving patients with chronic mild-to-moderate
      mental health problems in the research/policy process requires multiple user
      involvement strategies, including questionnaires but supplemented with interviews
      and discussion groups. CONCLUSION: Patients with common chronic mental health
      problems have a clear view about what constitutes quality general
      practice/practitioner care but highlighted quality deficits for people with
      chronic mental health conditions.

PMID- 18072699
TI  - To measure or not to measure? Reviewing the assessment of spirituality and
      religion in health-related quality of life.
AB  - Measures of quality of life have not conventionally or routinely included
      concepts of spirituality, religion, or existential wellbeing. Although
      spirituality has been seen as irrelevant, or difficult to measure, a growing body
      of peer-reviewed articles point to a positive and important relationship between
      spiritual beliefs and other domains of quality of life in health. Following a
      discussion of current theoretical issues surrounding the inclusion of these
      generic concepts, we select and review seven quality-of-life assessments in
      health that provide a spiritual and/or religious dimension, and evaluate each in
      psychometric terms. Such information could be useful to clinicians working in
      chronic illness, surgery and terminal care, who seek concept clarification before
      using an assessment that includes a spiritual domain.

PMID- 18072700
TI  - Accountability for patient self-management of chronic conditions; ethical
      analysis and a proposal.
AB  - Patient self-management (PSM) of varying portions of therapy for chronic illness
      is expanding. However, several current conditions of practice are ethically
      problematic. Standards remain process-oriented, and accountability for patient
      outcomes and quality of practice of both patient and provider is diffuse. PSM
      carries important benefits but largely unmonitored potential harms. Also, access
      to preparation for safe PSM appears to be skewed in favour of high socio-economic
      classes. This condition persists even though available evidence supports the
      conclusion that less advantaged patients with poor disease outcomes can be taught
      to self-manage, albeit they require more intensive and prolonged interventions.
      Routine clinical use of well-validated measurement instruments could serve to
      develop evidence-based standards of PSM, quality improvement and effective public
      policy. Development of a standard dataset would facilitate description of the
      effectiveness of existing programmes and comparison across programmes. Such
      reform will require investment in the development of instruments that measure
      patient ability to make sound clinical judgements and sustain PSM over changed
      disease and social conditions. It will take advantage of modem psychometric
      theory, which is increasingly necessary for building the empirical base for
      evidence-based healthcare.

PMID- 18072698
TI  - The impact of angina and cardiac history on health-related quality of life and
      depression in coronary heart disease patients.
AB  - OBJECTIVE: To prospectively examine the contribution of angina and cardiac
      history to health-related quality of life (HRQoL) and depression in cardiac
      patients, over 6 months post-hospitalization. METHODS: Participants were
      myocardial infarction (MI), percutaneous coronary intervention (PCI) or coronary
      artery bypass graft (CABG) outpatients under the age of 70 years. One hundred and
      seventy-one patients consented to participate, with 121 patients being retained 6
      months later (71% response rate). The impact of the patient's cardiac history and
      the presence of angina on physical, social and emotional HRQoL and depression was
      examined. RESULTS: At baseline, cardiac history was not significantly related to
      any of the dimensions of HRQoL or depression. At 6-month follow-up, cardiac
      history significantly predicted a higher level of depression, and angina was
      predictive of a significantly worse emotional, physical and social HRQoL and a
      higher level of depression. DISCUSSION: The presence of a cardiac history is
      associated with depression 6 months post-cardiac event, and angina is associated
      with both an adverse HRQoL and higher levels of depression. As past research has
      demonstrated that depression is a risk factor for mortality in patients with
      established heart disease, it is important from both a clinical and a research
      perspective to address these issues.

PMID- 18072701
TI  - Hospital activity and hospital profits.
AB  - The paper uses data from a cross section of southeastern hospitals to examine
      which activities are profitable for hospitals. The analysis suggests that
      hospitals may operate at less than profit-maximizing levels of output. In
      addition, contrary to popular belief emergency rooms are shown to be profit
      generating centers for hospitals.

PMID- 18072702
TI  - Why do patients select a hospital? A conjoint analysis in two German hospitals.
AB  - Patients decide on where to consume hospital services in Germany. Thus, the
      understanding of the exact hospital selection criteria and their weights is
      important. This research reviews the antecedents of hospital selection utilizing
      the conjoint methodology with regard to six questions. (1) Which are the relevant
      choice criteria, and (2) what are their weights? (3) Which criteria receive an
      increased importance in the absence of experience? (4) Do differences between
      compulsory and privately insured patients, (5) between hospitals with regard to
      their size, and (6) between female and male patients exist? The relevance and
      importance of nine pre-selected criteria are determined through two conjoint
      analyses. Experience is found to be most important followed by referral by
      general practitioner, certified quality management system, positive press
      coverage, recommendation by relatives and acquaintances and distance to the
      hospital. Reception area design and the personnel's friendliness, the website
      quality and the published quality report are less relevant. Without experience,
      reception area design, personnel's friendliness and distance to the hospital
      receive an increased importance. In addition, for some criteria notable
      discrepancies between female and male patients and between patients with
      different insurance policies are found.

PMID- 18072703
TI  - The power of creative medical education: how one retirement community is learning
      how to manage diabetes.
AB  - Although the NIH announced that it would launch a systematic campaign to fight
      obesity, which now affects nearly two-thirds of the U.S. population, one of the
      primary complications of obesity is diabetes, which has been a serious clinical
      issue for many years. While an array of pharmacotherapeutic interventions for
      diabetes treatment emerged over the last twenty years, the ongoing management of
      diabetes often depends upon the quality and accessibility of provider services
      offered by one's health plan. This article examines one retirement community's
      response to the educational needs of its diabetic residents. Through a series of
      ongoing, semi-structured and voluntary meetings, this community appears to
      effectively address the behavioral, social and interpersonal concerns of
      diabetics in a manner that can serve as a model for other and larger communities
      of its kind. Since diabetes has fast become a serious concern among various
      demographic groups, this manuscript will also review another educational
      initiative and make recommendations for implementing successful elements
      elsewhere.

PMID- 18072704
TI  - "When doing good is just the start to being good": a possible tool to improve the
      organizational effectiveness of non-profit health care organizations.
AB  - Health care is an area where many non-profit organizations do good work,
      relieving governments and for-profit providers of workload. They contribute often
      specific knowledge and competence or provide better access to patients through
      their cultural and ethnic affiliations. Non-profit organizations, NPOs, are often
      dependent on one or more significant donors, sometimes governments, sometimes for
      profit health providers and mostly private/corporate donors with an interest in
      specific medical areas, such as Alzheimers, or in unique communities, such as the
      Laotian neighborhoods in Southern California. In the media, high profile scandals
      involving financial irresponsibility have caused shock waves around the world.
      Concerns among some donors over the lack of a transparent performance measurement
      of non-profit entities have increased with the greater call for transparency and
      good governance in the corporate world. Not all the scandals have been in the
      commercial sector; some Not for Profit Organizations (NPOs) have been identified
      as having less than credible governance structures (Thomson, 2003). The watchdog
      organization SustainAbility reported that accountability and transparency are
      issues on which several NPOs are found wanting (Anon., 2003) and the New York
      Times reports that until recently NPOs were thought to be exempt from traditional
      oversight; their do-good nature and the commitment of their participants were
      thought to be sufficient to produce positive results (Christensen, 2004).

PMID- 18072705
TI  - Category Captain Management: a new approach for healthcare suppliers to partner
      with their hospital customers.
AB  - Hospitals represent a substantial market for pharmaceutical and medical device
      companies. The typical approach by healthcare manufacturers and suppliers to
      hospitals is to send representatives or detailers to hospitals and meet with
      representatives of hospital formularies and purchasing officials. Classic
      channels systems, and specifically, Category Captain Management ("CCM") may
      provide more of a sustainable competitive advantage than traditional hospital
      detailing. The purpose of this article is to discuss how CCM might apply as an
      approach for healthcare suppliers to truly partner with their hospital customers.

PMID- 18072706
TI  - U.S. health care, a different perspective.
AB  - The provision of health care in the United States has been misunderstood and
      misrepresented by many. Americans have the best health care in the world
      available to them on demand. What other country can provide such a privilege to
      its citizens? Americans are an insured people.

PMID- 18072707
TI  - How a rural general surgeon remains competitive.

PMID- 18072708
TI  - Surgery in a disaster: assessing the lessons of the Katrina event.

PMID- 18072709
TI  - Access: the key concept for the ACSPA-SurgeonsPAC.

PMID- 18072710
TI  - Do barrier drapes reduce surgical site infections?

PMID- 18072711
TI  - SDIF: one year later.

PMID- 18072712
TI  - Surgical lifestyles: surgeon doctors cars.

PMID- 18072713
TI  - Ovarian cancer is GCF's focus for gynecologic cancer awareness month.

PMID- 18072714
TI  - NTDB data points: the "university of injury".

PMID- 18072715
TI  - Flurbiprofen derivatives in Alzheimer's disease: synthesis, pharmacokinetic and
      biological assessment of lipoamino acid prodrugs.
AB  - Flurbiprofen (FLU) lipophilic prodrugs with lipoamino acids (LAA) 6a- e were
      synthesized for brain delivery. Chemical and plasmatic stability of prodrugs 6a-
      e as well as pharmacokinetic distribution studies for the prodrugs 6b and 6d were
      carried out. FLU prodrugs 6a- e were compared to the parent drug for their
      ability to inhibit binding of [F-18]FDDNP to in vitro formed beta-amyloid protein
      (Abeta fibrils). FLU-LAA conjugates showed a typical prodrug stability profile,
      being stable in PBS at pH 7.4 and releasing the active drug in plasma. Compound
      6d yielded a slow accumulation of FLU in the brain. In the in vitro inhibition
      assay, all prodrugs except for the prodrug with the longest alkyl side chain (
      6e) were effective as inhibitors of [F-18]FDDNP binding to Abeta fibrils with
      EC50 values in the 10-300 nM range. The different brain accumulation kinetics
      shown by FLU and its LAA conjugate 6d suggested a possible slow-releasing
      activity of FLU by these prodrugs in the brain or a differential pharmacological
      effect deserving further, detailed studies on their biodistribution and
      pharmacological profile.

PMID- 18072717
TI  - The synthesis and chelation chemistry of DOTA-peptide conjugates.
AB  - Metal complexes of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
      acid)-peptide conjugates are increasingly used as targeted imaging and
      therapeutic radiopharmaceuticals and MRI contrast agents. This review covers the
      bifunctional derivatives of DOTA, the solution and solid-phase synthesis of DOTA
      peptide conjugates, their coordination and chelation chemistry, and the
      biomedical applications of various DOTA-peptide conjugate metal complexes.

PMID- 18072716
TI  - Amino acid analysis of peptide loading ratios in conjugate vaccines: a comparison
      of direct electrochemical detection and 6-aminoquinolyl-N-hydroxysuccinimidyl
      carbamate pre-column derivatization methods.
AB  - Amino acid analysis using direct electrochemical detection was compared with
      precolumn fluorescent derivatization using 6-aminoquinolyl- N-hydroxysuccinimidyl
      carbamate (AQC) for evaluation of the degree of covalent coupling of peptides to
      a carrier-protein complex derived from the bacteria Neisseria meningitidis. AQC
      derivatization was found to give superior sensitivity compared to electrochemical
      detection, with less interference from sample components such as carbohydrates or
      buffer salts. Hydrolysis time and temperature were optimized for maximal
      recoveries of the marker amino acid 6-aminohexanoic acid (epsilon-Ahx) and the
      unique amino acids S-dicarboxyethyl cysteine (SDCEC) and S-carboxymethyl
      homocysteine (SCHMC), which are generated upon the hydrolysis of the covalent
      linkage between the peptide and the carrier protein. Quantitation of these amino
      acids enabled the determination of the ratio of peptide to protein in the
      conjugate samples.

PMID- 18072718
TI  - Design, synthesis, and anti-inflammatory properties of orally active 4
      (phenylamino)-pyrrolo[2,1-f][1,2,4]triazine p38alpha mitogen-activated protein
      kinase inhibitors.
AB  - A novel structural class of p38 mitogen-activated protein (MAP) kinase inhibitors
      consisting of substituted 4-(phenylamino)-pyrrolo[2,1- f][1,2,4]triazines has
      been discovered. An initial subdeck screen revealed that the oxindole-pyrrolo[2,1
      f][1,2,4]triazine lead 2a displayed potent enzyme inhibition (IC 50 60 nM) and
      was active in a cell-based TNFalpha biosynthesis inhibition assay (IC 50 210 nM).
      Replacement of the C4 oxindole with 2-methyl-5- N-methoxybenzamide aniline 9 gave
      a compound with superior p38 kinase inhibition (IC 50 10 nM) and moderately
      improved functional inhibition in THP-1 cells. Further replacement of the C6
      ester of the pyrrolo[2,1- f][1,2,4]triazine with amides afforded compounds with
      increased potency, excellent oral bioavailability, and robust efficacy in a
      murine model of acute inflammation (murine LPS-TNFalpha). In rodent disease
      models of chronic inflammation, multiple compounds demonstrated significant
      inhibition of disease progression leading to the advancement of 2 compounds 11b
      and 11j into further preclinical and toxicological studies.

PMID- 18072719
TI  - Synthesis and characterization of platinum(II) oxadiazoline complexes and their
      in vitro antitumor activity in platinum-sensitive and -resistant cancer cell
      lines.
AB  - A series of platinum(II) complexes bearing Delta (4)-1,2,4-oxadiazoline ligands
      have been synthesized and characterized. Their in vitro antitumor activity has
      been assessed in platinum-sensitive and -resistant human ovarian cancer cell
      lines (PEO1, PEOCisR, PEOCarboR, and SK-OV3), as well as in colon cancer (SW948)
      and testicular cancer cell lines (N-TERA). All compounds tested showed potent
      cytotoxicity in the platinum-sensitive cell lines and retained activity in the
      cisplatin- and carboplatin-resistant lines, with IC 50 values similar to the
      parental drug sensitive counterpart. We propose, therefore, that platinum(II)
      oxadiazoline complexes may possess a novel mechanism of action, which render them
      active in tumor cells, with resistance to currently used platinum anticancer
      agents.

PMID- 18072720
TI  - Stereospecific high-affinity TRPV1 antagonists: chiral N-(2-benzyl-3
      pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues.
AB  - Previously, we reported the thiourea antagonists 2a and 2b as potent and high
      affinity TRPV1 antagonists. For further optimization of the lead compounds, a
      series of their amide and alpha-substituted amide surrogates were investigated
      and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4
      (methylsulfonylamino)phenyl]propionamide analogues were characterized as potent
      and stereospecific rTRPV1 antagonists. In particular, compounds 72 and 73
      displayed high binding affinities, with K i values of 4.12 and 1.83 nM and potent
      antagonism with K i values of 0.58 and 5.2 nM, respectively, in rTRPV1/CHO cells.
      These values are comparable or more potent than those of 5-iodoRTX under the same
      assay conditions. A distinctive binding model that includes two hydrophobic
      pockets is proposed for this series of compounds based on docking studies of 57
      and 72 with a homology model of the TM3/4 region of TRPV1.

PMID- 18072721
TI  - Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: discovery
      of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H
      pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the
      treatment of hypercholesterolemia.
AB  - In light of accumulating evidence that aggressive LDL-lowering therapy may offer
      increased protection against coronary heart disease, we undertook the design and
      synthesis of a novel series of HMG-CoA reductase inhibitors based upon a
      substituted pyrazole template. Optimizing this series using both structure-based
      design and molecular property considerations afforded a class of highly
      efficacious and hepatoselective inhibitors resulting in the identification of (3
      R,5 R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2 H
      pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the
      treatment of hypercholesterolemia.

PMID- 18072722
TI  - Synthesis, conformational analysis, and biological evaluation of 1
      hexylindolactam-V10 as a selective activator for novel protein kinase C isozymes.
AB  - Conventional and novel protein kinase C (PKC) isozymes are the main targets of
      tumor promoters. We developed 1-hexylindolactam-V10 ( 5) as a selective activator
      for novel PKC isozymes that play important roles in various cellular processes
      related to tumor promotion, ischemia--reperfusion injury in the heart, and
      Alzheimer's disease. The compound existed as a mixture of three conformers. The
      trans-amide restricted analogues of 5 ( 14 and 15) hardly bound to PKC isozymes,
      suggesting that the active conformation of 5 could be that with a cis-amide.
      Compound 5 selectively translocated novel PKC isozymes over conventional PKC
      isozymes in HeLa cells at 0.1-1 microM. These results suggest that 5 could be
      useful for the functional analysis of novel PKC isozymes.

PMID- 18072723
TI  - Nonalcoholic fatty liver disease: pathogenesis and potential for nuclear
      receptors as therapeutic targets.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a consequence of insulin resistance
      encompassing a spectrum that extends from simple hepatic steatosis through to
      nonalcoholic steatohepatitis (NASH), a condition that may progress to cirrhosis
      with its associated complications. A subset of nuclear receptors act as
      intracellular sensors for cholesterol metabolites, free fatty acids, and a range
      of other lipophilic molecules with pivotal roles in energy homeostasis and
      inflammation. These receptors represent attractive drug targets for the
      management of NAFLD and NASH as well as related conditions such as type 2
      diabetes and the broader metabolic syndrome. To date, human studies have
      concentrated on peroxisome proliferator-activated receptor (PPAR) agonists,
      particularly those directed at PPARgamma. However, these drugs have significant
      limitations, so alternate approaches to nuclear receptor targeting are being
      explored.

PMID- 18072724
TI  - BRET-based method for detection of specific RNA species.
AB  - RNA detection and quantitation is a common necessity in modern molecular biology
      research. Most methods, however, are complex and/or time-intensive. Presented
      here is a BRET (bioluminescene resonance energy transfer)-based method that can
      accomplish the task of RNA identification quickly and easily. By conjugating BRET
      enzymes to two different oligonucleotides that are complementary to the same
      target sequence, probes were developed that could detect RNA using a solution
      based assay. This assay was optimized for spacer length between the binding sites
      (found to be 10 nucleotides), and sensitivity was determined to be 1 microg for a
      specific species of RNA within a mixed population. Specificity of the assay was
      assessed using in vitro transcribed cRNA and found to be statistically
      siginificant ( p = 3.11 x 10 (-6), ANOVA, multiple range test). This assay
      represents a possibility for a less technically demanding, streamlined
      alternative to canonical RNA assays.

PMID- 18072726
TI  - New celecoxib derivatives as anti-inflammatory agents.
AB  - A series of 1,5-diarylpyrazoles with a substituted benzenesulfonamide moiety was
      synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities.
      Some compounds, for example, (+/-)-2-[4-(5- p-tolyl-3-trifluoromethyl-pyrazole-1
      yl)-benzenesulfonylaminooxy]-propionic acid 16 and its disodium salt 21, had a
      higher in vivo anti-inflammatory activity compared to celecoxib, despite having
      no in vitro COX-1 or COX-2 inhibitory activity. Their gastrointestinal side
      effect profile is essentially more favorable than that of celecoxib.

PMID- 18072725
TI  - Streptavidin in antibody pretargeting. 5. chemical modification of recombinant
      streptavidin for labeling with the alpha-particle-emitting radionuclides 213Bi
      and 211At.
AB  - We are investigating the use of recombinant streptavidin (rSAv) as a carrier
      molecule for the short-lived alpha-particle-emitting radionuclides 213Bi ( t 1/2
      = 45.6 min) and 211At ( t 1/2 = 7.21 h) in cancer therapy. To utilize rSAv as a
      carrier, it must be modified in a manner that permits rapid chelation or bonding
      with these short-lived radionuclides and also modified in a manner that
      diminishes its natural propensity for localization in the kidney. Modification
      for labeling with (213)Bi was accomplished by conjugation of rSAv with the DTPA
      derivative p-isothiocyanato-benzyl-CHX-A'' (CHX-A''), 3a. Modification for direct
      labeling with 211At was accomplished by conjugation of rSAv with an
      isothiocyanatophenyl derivative of a nido-carborane (nCB), 3b, or an
      isothiocyanatophenyl-dPEG/decaborate(2-) derivative, 3c. After conjugation of the
      chelating or bonding moiety, rSAv was further modified by reaction with an excess
      (50-100 equivalents) of succinic anhydride. Succinylation of the lysine amines
      has previously been shown to greatly diminish kidney localization. rSAv modified
      by conjugation with 3a and succinylated rapidly radiolabeled with 213Bi (<5 min),
      providing a 72% isolated yield. 211At labeling of modified rSAv was accomplished
      in aqueous solution using chloramine-T as the oxidant. Astatination of rSAv
      conjugated with 3b and succinylated occurred very rapidly (<1 min), providing a
      50% isolated radiochemical yield. Astatination of rSAv conjugated with 3c and
      succinylated was also very rapid (<1 min) providing 66-71% isolated radiochemical
      yields. Astatination of succinylated rSAv, 2a, which did not have conjugated
      borane cage moieties, resulted in a much lower radiolabeling yield (18%). The
      213Bi or 211At-labeled modified rSAv preparations were mixed with the
      corresponding 125 I-labeled rSAv, and dual-label in vivo distributions were
      obtained in athymic mice. The in vivo data show that 213Bi-labeled succinylated
      rSAv [ 213Bi] 6a has tissue concentrations similar to those of 125 I-labeled
      modified rSAv [ 125 I] 6b, suggesting that (213)Bi is quite stable toward release
      from the chelate in vivo. In vivo data also indicate that the (211)At-labeled
      rSAv conjugated with 3b or 3c and succinylated are stable to in vivo
      deastatination, whereas succinylated rSAv lacking a boron cage moiety is subject
      to some deastatination. The modified rSAv conjugated with nido-carborane
      derivative 3b has a higher retention in many tissues than rSAv without the
      carborane conjugated. Interestingly, the rSAv conjugated with 3c, which also
      contains an m-dPEG 12 moiety, has significantly decreased concentrations in blood
      and other tissues when compared with those of direct-labeled rSAv, suggesting
      that it may be a good candidate for further study. In conclusion, rSAv that has
      been modified with CHX-A'' and succinylated (i.e., 5a) may be useful as a carrier
      of 213Bi. The encouraging results obtained with the PEGylated decaborate(2-)
      derivative 3c and succinylated (i.e., 5c) suggests that its further study as a
      carrier of 211At in pretargeting protocols is warranted.

PMID- 18072727
TI  - Design, synthesis, and biological evaluation of classical and nonclassical 2
      amino-4-oxo-5-substituted-6-methylpyrrolo[3,2-d]pyrimidines as dual thymidylate
      synthase and dihydrofolate reductase inhibitors.
AB  - We designed and synthesized a classical antifolate N-{4-[(2-amino-6-methyl-4-oxo
      3,4-dihydro-5 H-pyrrolo[3,2- d]pyrimidin-5-yl)methyl]benzoyl}- l-glutamic acid 4
      and 11 nonclassical analogues 5- 15 as potential dual thymidylate synthase (TS)
      and dihydrofolate reductase (DHFR) inhibitors. The key intermediate in the
      synthesis was N-(4-chloro-6-methyl-5 H-pyrrolo[3,2- d]pyrimidin-2-yl)-2,2
      dimethylpropanamide, 29, to which various 5-benzyl substituents were attached.
      For the classical analogue 4, the ester obtained from the N-benzylation reaction
      was deprotected and coupled with diethyl l-glutamate followed by saponification.
      Compound 4 was a potent dual inhibitor of human TS (IC 50 = 46 nM, about 206-fold
      more potent than pemetrexed) and DHFR (IC 50 = 120 nM, about 55-fold more potent
      than pemetrexed). The nonclassical analogues were marginal inhibitors of human
      TS, but four analogues showed potent T. gondii DHFR inhibition along with >100
      fold selectivity compared to human DHFR.

PMID- 18072728
TI  - Structure-activity relationship of a series of synthetic lipopeptide self
      adjuvanting group a streptococcal vaccine candidates.
AB  - The development of 16 self-adjuvanting group A streptococcal vaccine candidates,
      composed of (i) a universal helper T-cell epitope (P25), (ii) a target GAS B-cell
      epitope (J14), and (iii) a lipid moiety, is described. Systemic J14-specific IgG
      antibodies were detected following subcutaneous immunization of BALB/c (H-2 (d))
      mice with each construct without the need for an additional adjuvant. The effect
      of changing the order of P25, J14, and lipid moiety attachment or incorporation
      of P25 and J14 into a lipid-core peptide system on antibody titers was assessed.
      The point of lipid moiety attachment had the greatest influence on systemic J14
      specific IgG antibody titers. Overall, the best vaccines featured a C-terminal
      lipid moiety, conjugated through a lysine residue to P25 at the N-terminus, and
      J14 on the lysine side chain.

PMID- 18072730
TI  - Further structure-activity relationships study of hybrid 7-{[2-(4-phenylpiperazin
      1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol analogues:
      identification of a high-affinity D3-preferring agonist with potent in vivo
      activity with long duration of action.
AB  - This paper describes an extended structure-activity relationships study of
      aminotetralin-piperazine-based hybrid molecules developed earlier for dopamine
      D2/D3 receptors. Various analogues as positional isomers have been developed
      where location of the phenolic hydroxyl group has been varied on the aromatic
      ring. Between two catechol derivatives, compound 6e with a two methylene linker
      length exhibited higher affinity and selectivity for D3 over D2 receptors over
      compound 6f with four methylene linkers (D2/D3 = 50.6 vs 7.51 for 6e and 6f,
      respectively). In general, the (-)-isomer was more potent than the (+)-isomeric
      counterpart. Binding results indicated highest selectivity for D3 receptors in
      compound (-)- 10 ( K i = 0.35 nM; D2/D3 = 71). In the 5-hydroxy series, highest
      selectivity for D3 receptors was exhibited by compound (-)- 25 ( K i = 0.82 nM;
      D2/D3 = 31.5). Most potent compounds exhibited binding and functional affinities
      at the sub-nanomolar level for the D3 receptor. Binding assays were carried out
      with HEK-293 cells expressing either D2 or D3 receptors by using tritiated
      spiperone as radioligand for competition studies to evaluate inhibition constants
      ( K i). A functional assay of selected compounds for stimulating GTPgammaS
      binding was carried out with CHO cells expressing human D2 receptors and AtT-20
      cells expressing human D3 receptors. The functional assay results indicated
      partial to full agonist characteristics of test compounds. Compound (-)- 25 was
      selected further for in vivo study to evaluate its potency in producing
      contralateral rotations in rats with unilateral lesion in the nigrostriatal
      region induced by neurotoxin 6-OHDA, a Parkinsonian animal model. Compound (-)-
      25 at 5 micromol/kg exhibited rotational activity that lasted beyond 12 h,
      whereas at a 1 micromol/kg dose the rotations lasted beyond 8 h.

PMID- 18072731
TI  - Antiviral phagocytosis is regulated by a novel Rab-dependent complex in shrimp
      penaeus japonicus.
AB  - Rab GTPases are involved in phagosome formation and maturation. However, the role
      of Rab GTPases in phagocytosis against virus infection remains unknown. In this
      study, it was found that a Rab gene ( PjRab) from marine shrimp was upregulated
      in virus-resistant shrimp, suggesting that Rab GTPase was involved in the innate
      response to virus. The RNAi and mRNA assays revealed that the PjRab protein could
      regulate shrimp hemocytic phagocytosis through a protein complex consisting of
      the PjRab, beta-actin, tropomyosin, and envelope protein VP466 of shrimp white
      spot syndrome virus (WSSV). It was further demonstrated that the PjRab gene
      silencing by RNAi caused the increase in the number of WSSV copies, indicating
      that the PjRab might be an intracellular virus recognition protein employed by a
      host to increase the phagocytic activity. Therefore, our study presents a novel
      Rab-dependent signaling complex, in which the Rab GTPase might detect virus
      infection as an intracellular virus recognition protein and trigger downstream
      phagocytic defense against virus in crustacean for the first time. This discovery
      would improve our understanding of the still poorly understood molecular events
      involved in innate immune response against virus infection of invertebrates.

PMID- 18072734
TI  - Effect of bentonite characteristics on the elemental composition of wine.
AB  - Physical, chemical, and mineralogical characteristics of six bentonites were
      assessed and related to their elemental release to wine. Extraction essays of
      bentonites in wine at three pH levels were carried out. The multielemental
      analysis of bentonites and wines was performed by atomic absorption spectrometry
      (AAS) and inductively coupled plasma mass spectrometry (ICP-MS). Bentonite
      addition resulted in significantly higher concentrations of Li, Be, Na, Mg, Al,
      Ca, Sc, V, Mn, Fe, Co, Ni, Ga, Ge, As, Sr, Y, Zr, Nb, Mo, Cd, Sn, Sb, Ba, W, Tl,
      Bi, and W. In contrast, the concentrations of B, K, Cu, Zn, and Rb significantly
      decreased. A strong correlation between Na concentrations of treated wines and
      its content in bentonite exchange complex was observed. Al and Fe contents
      reflected bentonite extractable aluminous and ferruginous constituents, while Be,
      Mg, Ca, V, Mn, Ni, Ge, Zr, Nb, Mo, Sn, Sb, Tl, Pb, and U concentrations reflected
      the elemental composition of bentonites. Several nonconformances with OIV
      specifications demonstrated the need for an effective control.

PMID- 18072732
TI  - Identification and characterization of disulfide bonds in proteins and peptides
      from tandem MS data by use of the MassMatrix MS/MS search engine.
AB  - A new database search algorithm has been developed to identify disulfide-linked
      peptides in tandem MS data sets. The algorithm is included in the newly developed
      tandem MS database search program, MassMatrix. The algorithm exploits the
      probabilistic scoring model in MassMatrix to achieve identification of disulfide
      bonds in proteins and peptides. Proteins and peptides with disulfide bonds can be
      identified with high confidence without chemical reduction or other
      derivatization. The approach was tested on peptide and protein standards with
      known disulfide bonds. All disulfide bonds in the standard set were identified by
      MassMatrix. The algorithm was further tested on bovine pancreatic ribonuclease A
      (RNaseA). The 4 native disulfide bonds in RNaseA were detected by MassMatrix with
      multiple validated peptide matches for each disulfide bond with high statistical
      scores. Fifteen nonnative disulfide bonds were also observed in the protein
      digest under basic conditions (pH = 8.0) due to disulfide bond interchange. After
      minimizing the disulfide bond interchange (pH = 6.0) during digestion, only one
      nonnative disulfide bond was observed. The MassMatrix algorithm offers an
      additional approach for the discovery of disulfide bond from tandem mass
      spectrometry data.

PMID- 18072735
TI  - Yield and oil composition of 38 basil (Ocimum basilicum L.) accessions grown in
      Mississippi.
AB  - A field experiment was conducted to assess yield, oil content, and composition of
      38 genotypes of sweet basil ( Ocimum basilicum L.). Overall, biomass yields were
      high and comparable to those reported in the literature. However, basil genotypes
      differed significantly with respect to oil content and composition. Oil content
      of the tested accessions varied from 0.07% to 1.92% in dry herbage. On the basis
      of the oil composition, basil accessions were divided into seven groups: (1) high
      linalool chemotype [19-73% (-)-linalool], (2) linalool-eugenol chemotype [six
      chemotypes with 28-66% (-)-linalool and 5-29% eugenol], (3) methyl chavicol
      chemotype [six accessions with 20-72% methyl chavicol and no (-)-linalool], (4)
      methyl chavicol-linalool chemotype [six accessions with 8-29% methyl chavicol and
      8-53% (-)-linalool], (5) methyl eugenol-linalool chemotype [two accessions with
      37% and 91% methyl eugenol and 60% and 15% (-)-linalool], (6) methyl cinnamate
      linalool chemotype [one accession with 9.7% methyl cinnamate and 31% (-)
      linalool], and (7) bergamotene chemotype [one accession with bergamotene as major
      constituent, 5% eucalyptol, and <1% (-)-linalool]. Our results demonstrated that
      basil could be a viable essential oil crop in Mississippi. The availability of
      various chemotypes offers the opportunity for production of basil to meet the
      market requirements of specific basil oils or individual compounds such as (-)
      linalool, eugenol, methyl chavicol, methyl cinnamate, or methyl eugenol.

PMID- 18072736
TI  - Antioxidant activity of tartary (Fagopyrum tataricum (L.) Gaertn.) and common
      (Fagopyrum esculentum moench) buckwheat sprouts.
AB  - This study compared the differences of two types of buckwheat sprouts, namely,
      common buckwheat ( Fagopyrum esculentum Moench) and tartary buckwheat ( Fagopyrum
      tataricum (L.) Gaertn.), in general composition, functional components, and
      antioxidant capacity. The ethanol extracts of tartary buckwheat sprouts (TBS) had
      higher reducing power, free radical scavenging activity, and superoxide anion
      scavenging activity than those of common buckwheat sprouts (CBS). As for
      chelating effects on ferrous ions, CBS had higher values than TBS. Rutin was the
      major flavonoid found in these two types of buckwheat sprouts, and TBS was 5 fold
      higher in rutin than CBS. The antioxidant effects of buckwheat sprouts on human
      hepatoma HepG2 cells revealed that both of TBS and CBS could decrease the
      production of intracellular peroxide and remove the intracellular superoxide
      anions in HepG2 cells, but TBS reduced the cellular oxidative stress more
      effectively than CBS, possibly because of its higher rutin (and quercetin)
      content.

PMID- 18072737
TI  - Enzymatic synthesis and properties of highly branched rice starch amylose and
      amylopectin cluster.
AB  - We enzymatically modified rice starch to produce highly branched amylopectin and
      amylose and analyzed the resulting structural changes. To prepare the highly
      branched amylopectin cluster (HBAPC), we first treated waxy rice starch with
      Thermus scotoductus alpha-glucanotransferase (TSalphaGT), followed by treatment
      with Bacillus stearothermophilus maltogenic amylase (BSMA). Highly branched
      amylose (HBA) was prepared by incubating amylose with Bacillus subtilis 168
      branching enzyme (BBE) and subsequently treating it with BSMA. The molecular
      weight of TSalphaGT-treated waxy rice starch was reduced from 8.9 x 10(8) to 1.2
      x 10(5) Da, indicating that the alpha-1,4 glucosidic linkage of the segment
      between amylopectin clusters was hydrolyzed. Analysis of the amylopectin cluster
      side chains revealed that a rearrangement in the side-chain length distribution
      occurred. Furthermore, HBAPC and HBA were found to contain significant numbers of
      branched maltooligosaccharide side chains. In short, amylopectin molecules of
      waxy rice starch were hydrolyzed into amylopectin clusters by TSalphaGT in the
      enzymatic modification process, and then further branched by transglycosylation
      using BSMA. HBAPC and HBA showed higher water solubility and stability against
      retrogradation than amylopectin clusters or branched amylose. The hydrolysis
      rates of HBAPC and HBA by glucoamylase and alpha-amylase greatly decreased. The k
      cat/ K m value of glucoamylase acting on the amylopectin cluster was 45.94 s(
      1)(mg/mL)(-1) and that for glucoamylase acting on HBAPC was 11.10 s(-1)(mg/mL)(
      1), indicating that HBAPC was 4-fold less susceptible to glucoamylase. The k cat/
      K m value for HBA was 15.90 s(-1)(mg/mL)(-1), or about three times less than that
      for branched amylose. The k cat/ K m values of porcine pancreatic alpha-amylase
      for HBAPC and HBA were 496 and 588 s(-1)(mg/mL)(-1), respectively, indicating
      that HBA and HBAPC are less susceptible to hydrolysis by glucoamylase and alpha
      amylase. HBAPC and HBA show potential as novel glucan polymers with low
      digestibility and high water solubility.

PMID- 18072738
TI  - Two new Monascus metabolites with strong blue fluorescence isolated from red
      yeast rice.
AB  - Red yeast rice obtained as cultures of Monascus AS3.4444 on rice was extracted
      and analyzed by high-performance liquid chromatography (HPLC). Two new Monascus
      metabolites with similar fluorescence spectra (lambda ex = 396 nm, lambda em =
      460 nm) and UV absorption spectra (lambda max = 386 nm) were detected. They were
      isolated by rechromatography on a silica gel column and semipreparative HPLC, and
      two strong blue fluorescent compounds were obtained. Their structures were
      elucidated by electrospray ionization mass spectrometry (ESI-MS), electrospray
      ionization tandem mass spectrometry (ESI-MS/MS), intensive ESI-MS, and nuclear
      magnetic resonance spectroscopy ( (1)H NMR, (13)C NMR, COSY, and HMBC) studies.
      High-resolution mass spectrometry indicated the molecular formulas C 21H 24O 5
      and C 23H 28O 5. The two new compounds, named monasfluore A and monasfluore B,
      respectively, contain a alkyl side chain, gamma-lactone, and propenyl group,
      whereas the more lipophilic compound, monasfluore B, is a higher homologue of
      monasfluore A, with the more lipophilic octanoyl instead of the hexanoyl side
      chain.

PMID- 18072739
TI  - Purification and characterization of a cysteine protease inhibitor from chum
      salmon (Oncorhynchus keta) plasma.
AB  - A cysteine protease inhibitor (CPI) in chum salmon ( Oncorhynchus keta) plasma
      (CSP) was detected after performing inhibitory activity staining against papain
      under nonreducing condition. The CPI was purified from CSP by affinity
      chromatography with a yield and purification ratio of 0.94% and 30.36-fold,
      respectively. CSP CPI had a molecular mass of 70 kDa based on the results of SDS
      PAGE and Sephacryl S-100 gel filtration. CSP CPI was a glycoprotein based on the
      periodic acid-Schiff (PAS) staining of the SDS-PAGE gel and classified as a
      kininogen. CSP CPI was stable in the pH range of 6.0-9.0 with maximal stability
      at pH 7.0. CSP CPI presented thermal stability at temperatures below 50 degrees C
      and exhibited maximal activity at temperatures of 20-40 degrees C. CSP CPI was
      determined to be a noncompetitive inhibitor against papain, with an inhibitor
      constant (Ki) of 105 nM.

PMID- 18072740
TI  - Concentrations of metals (zinc, copper, cadmium, and mercury) in three domestic
      ducks in France: Pekin, Muscovy, and Mule ducks.
AB  - The role of different factors such as biological material (tissues, organs) and
      trophic condition (overfeeding or not) in the metal accumulation was studied in
      three genotypes of ducks (Pekin, Muscovy, and Mule) under breeding conditions.
      Results showed that overfeeding decreased the concentration in Cd, Cu, and Zn
      through the dilution process. In contrast, mercury concentration increased with
      this method. A relation between lipidic metabolism of genotypes and the
      distribution of this metal in biological material was found. Domestic ducks were
      little contaminated, but a low chronic contamination in Cd was observed, probably
      coming from the food. Due to the low levels of contamination observed in these
      breeding ducks, they can be considered as a good control for further
      contamination studies and comparison with accumulation levels recorded in the
      field. The impact of feeding condition on accumulation showed the importance of
      taking into account the life cycle of birds before studying their contamination
      and the impact of pollutants.

PMID- 18072741
TI  - Analysis of anthocyanin variation in wild populations of bilberry (Vaccinium
      myrtillus L.) in Finland.
AB  - The berries of Vaccinium myrtillus L. are characterized by 15 anthocyanins. To
      study the variation in the anthocyanins on a south-north axis of about 1000 km in
      Finland, the berries from 179 individual bilberry plants in 20 populations were
      analyzed using an optimized RP-HPLC-DAD method. The mean content of the total
      anthocyanins was 2878 mg/100 g dry weight. There was extensive variation in the
      anthocyanin contents within and between the populations, suggesting differences
      in berry raw material. A significantly lower content of the total anthocyanins
      was observed in the berries of the southern region compared to those in the
      central and northern regions. Differences in the proportions of anthocyanins were
      also observed. The delphinidin glycosides dominated in the northern berries
      whereas the cyanidin glycosides were most common in the southern ones.
      Exceptional bilberry individuals were found mainly from eastern Finland with very
      low amounts of anthocyanidin glucosides. This is the first systematic study to
      reveal the extremely high variation in the content and distribution of
      anthocyanins in wild bilberries.

PMID- 18072742
TI  - Survey results of benzene in soft drinks and other beverages by headspace gas
      chromatography/mass spectrometry.
AB  - Benzene, a carcinogen that can cause cancer in humans, may form at nanogram per
      gram levels in some beverages containing both benzoate salts and ascorbic or
      erythorbic acids. Through a series of reactions, a hydroxyl radical forms that
      can decarboxylate benzoate to form benzene. Elevated temperatures and light
      stimulate these reactions, while sugar and ethylenediaminetetraacetic acid (EDTA)
      can inhibit them. A headspace gas chromatography/mass spectrometry method for the
      determination of benzene in beverages was developed and validated. The method was
      used to conduct a survey of 199 soft drinks and other beverages. The vast
      majority of beverages sampled contained either no detectable benzene or levels
      below the U.S. Environmental Protection Agency's drinking water limit of 5 ng/g.
      Beverages found to contain 5 ng/g benzene or more were reformulated by the
      manufacturers. The amount of benzene found in the reformulated beverages ranged
      from none detected to 1.1 ng/g.

PMID- 18072743
TI  - Use of near-isogenic wheat lines to determine the glutenin composition and
      functionality requirements for flour tortillas.
AB  - In wheat ( Triticum aestivum L), the synthesis of high molecular weight (HMW)
      glutenins (GS) is controlled by three heterologous genetic loci present on the
      long arms of group 1 wheat chromosomes. The loci Glu-A1, Glu-B1, and Glu-D1 and
      their allelic variants play important roles in the functional properties of wheat
      flour. This study focused on understanding the functionality of these protein
      subunits on tortilla quality. Near-isogenic wheat lines in which one or more of
      these loci were absent or deleted were used. Tortillas were prepared from each
      deletion line and the parent lines. The elimination of certain HMW-GS alleles
      alter distinct but critical aspects of tortilla quality such as diameter, shelf
      stability, and overall quality. Two deletion lines possessing HMW-GS 17 + 18 at
      Glu-B1 and deletions in Glu-A1 and Glu-D1 had significantly larger tortilla
      diameters, yet tortilla shelf life was compromised or unchanged from the parent
      lines used to develop the deletion lines or the commercial tortilla flour used as
      a control. Alternatively, a deletion line possessing Glu-A1 and Glu-D1 (HMW-GS 1,
      5 + 10) and a deletion in Glu-B1 also significantly improved tortilla diameters.
      Whereas the increase in diameter was less than the line possessing only HMW-GS 17
      + 18 at Glu-B1, the stability of the tortillas were, however, maintained and
      improved as compared to the parent lines containing a full compliment of HMW-GS.
      Thus, the presence of subunits 5 + 10 at Glu-D1 alone or in combination with
      subunit 1 at Glu-A1 appears to provide a compromise of improvement in dough
      extensibility for improved tortilla diameters while also providing sufficient
      gluten strength to maintain ideal shelf stability.

PMID- 18072744
TI  - Immunoreactivity and amino acid content of fermented soybean products.
AB  - Food allergy has become a public health problem that continues to challenge both
      the public and the food industry. The objective of this research was the
      detection and quantification of the major human allergenic soy proteins and to
      study the reduction in immunoreactivity and improvement of amino acid content
      after fermentation of soybean flour. Fermentation was carried out in the solid
      state of cracked seeds inoculated with Aspergillus oryzae, Rhizopus oryzae, and
      Bacillus subtilis and in the liquid state of milled soybean flours fermented
      naturally by microorganisms present only in the seeds or by inoculation with
      Lactobacillus plantarum. ELISA and Western blot were used to quantify IgE
      antibody response, and HPLC was used to identify and quantify total amino acids.
      L. plantarum fermented soy flour showed the highest reduction in IgE
      immunoreactivity (96-99%) depending upon the sensitivity of the plasma used.
      Among the solid fermented products, the lowest reduction in immunoreactivity was
      obtained when mold strains, R. oryzae and A. oryzae, were used (66 and 68%,
      respectively, for human plasma 97.5 kUA/L). Among the solid fermented products,
      those inoculated with B. subtilis yielded a 81 and 86% reduction in
      immunoreactivity against both human plasma 97.5 IgE kUA/L and human pooled plasma
      samples, respectively. When soybean was subjected to liquid fermentation, most of
      the total amino acids increased significantly ( p < or = 0.05). In solid
      fermentation with R. oryzae, only Ala and Thr content improved. Fermentation can
      decrease soy immunoreactivity, and there is potential of developing nutritious
      hypoallergenic soy products.

PMID- 18072745
TI  - New cyclic peptides from the seeds of Annona squamosa L. and their anti
      inflammatory activities.
AB  - Two new cyclic peptides, cyclosquamosin H ( 1) and I ( 2), together with six
      known cyclic peptides, squamin A ( 3), squamin B ( 4), cyclosquamosin A ( 6),
      cyclosquamosin D ( 7), cyclosquamosin E ( 8), and cherimolacyclopeptide B ( 9),
      were isolated from the seeds of Annona squamosa. All structures were confirmed by
      2D nuclear magnetic resonance, chemical evidence, and electrospray ionization
      mass spectromotry/mass spectrometry (ESI-MS/MS). Compound 9 was isolated from
      this plant for the first time. In the anti-inflammatory assay, compound 7 showed
      an inhibitory effect on the production of pro-inflammatory cytokines within
      lipopolysaccharide and Pam3Cys-stimulated J774A.1 macrophages.

PMID- 18072746
TI  - Pharmacokinetics of saquinavir after intravenous and oral dosing of saquinavir:
      hydroxybutenyl-beta-cyclodextrin formulations.
AB  - The current research evaluated the ability of hydroxybutenyl-beta-cyclodextrin
      (HBenBCD) to enhance saquinavir in vitro solubility and in vivo oral
      bioavailability; both the base and mesylate salt forms of saquinavir were
      investigated. HBenBCD was effective and significantly improved saquinavir
      solubility in aqueous media. In the presence of 10 wt % HBenBCD, saquinavir base
      solubility in water was increased to ca. 5.5 +/- 0.4 mg/mL and represents a 27
      fold increase from that observed in water (207 +/- 5 microg/mL) in the absence of
      HBenBCD. Saquinavir-HBenBCD formulations were found to have rapid dissolution
      over a wide pH range (1.2-6.8), and saquinavir solubility in these media was
      maintained throughout the experiments. When saquinavir-HBenBCD formulations were
      administered to Wistar-Hannover rats, saquinavir was rapidly absorbed and rapidly
      eliminated. Rapid saquinavir elimination was particularly pronounced when
      saquinavir-HBenBCD formulations were given as an oral aqueous gavage. Saquinavir
      oral bioavailability in rats obtained from saquinavir mesylate capsules (2.0% +/-
      0.7%) was increased (9 +/- 4)-fold (18.6% +/- 7.3%) when dosed with saquinavir
      base-HBenBCD capsules. Clearly, HBenBCD can significantly improve the solubility
      and oral bioavailability of saquinavir; however, further formulation studies are
      required to optimize saquinavir oral delivery using this technology.

PMID- 18072747
TI  - Synthesis and evaluation of novel biodegradable hydrogels based on poly(ethylene
      glycol) and sebacic acid as tissue engineering scaffolds.
AB  - Novel biodegradable poly(ethylene glycol) (PEG) based hydrogels, namely, PEG
      sebacate diacrylate (PEGSDA) were synthesized, and their properties were
      evaluated. Chemical structures of these polymers were confirmed by Fourier
      transform infrared and proton nuclear magnetic resonance (1H NMR) spectroscopy.
      After photopolymerization, the dynamic shear modulus of the hydrogels was up to
      0.2 MPa for 50% PEGSDA hydrogel, significantly higher than conventional hydrogels
      such as PEG diacrylate (PEGDA). The swelling ratios of these macromers were
      significantly lower than PEGDA. The in vitro degradation study demonstrated that
      these hydrogels were biodegradable with weight losses about 66% and 32% for 25%
      and 50% PEGSDA after 8 weeks of incubation in phosphate-buffered saline at 37
      degrees C. In vitro biocompatibility was assessed using cultured rat bone marrow
      stromal cells (MSCs) in the presence of unreacted monomers or degradation
      products. Unlike conventional PEGDA hydrogels, PEGSDA hydrogel without RGD
      peptide modification induced MSC cell adhesion similar to tissue culture
      polystyrene. Finally, complex three-dimensional structures of PEGSDA hydrogels
      using solid free form technique were fabricated and their structure integrity was
      better maintained than PEGDA hydrogels. These hydrogels may find use as scaffolds
      for tissue engineering applications.

PMID- 18072748
TI  - PXR and LXR in hepatic steatosis: a new dog and an old dog with new tricks.
AB  - PXR was isolated as a "xenobiotic receptor" that regulates drug-metabolizing
      enzymes and transporters, whereas LXR is known to promote hepatic lipogenesis by
      activating the lipogenic transcriptional factor sterol regulatory element-binding
      protein (SREBP). We have recently shown that PXR can mediate a SREBP-independent
      lipogenic pathway by activating the free fatty acid (FFA) uptake transporter
      CD36, PPARgamma, and several accessory lipogenic enzymes, such as stearoyl CoA
      desaturase-1 (SCD-1) and long-chain free fatty acid elongase (FAE). More
      recently, we found activation of LXR also induced the expression of CD36.
      Promoter analysis established CD36 as a novel transcriptional target of LXRalpha.
      Moreover, the steatotic effect of LXR agonists was largely abolished in CD36 null
      mice, suggesting an essential role for CD36 and FFA uptake in LXR-mediated
      steatosis. We also showed that PPARgamma, a positive regulator of CD36, is also a
      transcriptional target of PXR. Thus, PXR can regulate CD36 directly or through
      its activation of PPARgamma. Interestingly, PXR- and LXR-mediated CD36 activation
      and PXR-mediated PPARgamma activation are all liver-specific. We conclude that
      CD36 is a shared target of LXR, PXR, and PPARgamma. The network of CD36
      regulation controlled by LXR, PXR, and PPARgamma establishes this FFA transporter
      as a common target of orphan nuclear receptors in their mediation of hepatic
      steatosis. It is hoped that the nuclear receptor-mediated CD36 regulation may
      offer novel targets for the therapeutic management of alcoholic and nonalcoholic
      steatosis.

PMID- 18072749
TI  - Regulation of transporters by nuclear hormone receptors: implications during
      inflammation.
AB  - Membrane transporters play a critical role in the absorption, distribution, and
      elimination of both endogenous substrates and xenobiotics. Defects in transporter
      function can lead to altered drug disposition including toxicity or loss of
      efficacy. Inflammation is one condition during which variable drug response has
      been demonstrated, and this can be attributed, at least in part, to changes in
      the expression of transporter genes. Thus, knowledge of the mechanisms behind
      transporter regulation can significantly contribute to our ability to predict
      variations in drug disposition among individuals and during inflammatory disease.
      The discovery of several xenobiotic-activated nuclear hormone receptors during
      the past decade including the pregnane X receptor, constitutive androstane
      receptor, and farnesoid X receptor has contributed greatly toward this endeavor.
      These receptors regulate the expression of transporters such as P-glycoprotein,
      MRP2, MRP3, BCRP, and OATP2 (Oatp1a1/OATP1B1), all of which undergo altered
      expression during an inflammatory response. Nuclear receptors may therefore play
      an important role in mediating this effect. This review presents what is
      currently known about the role of nuclear receptors in transporter regulation
      during inflammation. The use of this knowledge toward understanding
      interindividual variation in drug response and drug interactions during
      inflammation as well toward the development of therapeutics to treat transporter
      related diseases will also be discussed.

PMID- 18072750
TI  - Significance of prolyl hydroxylase 2 in the interference of aryl hydrocarbon
      receptor and hypoxia-inducible factor-1 alpha signaling.
AB  - Hypoxia-inducible factor-1 alpha (HIF-1 alpha) and the aryl hydrocarbon receptor
      (AhR) work as environmental sensors in human tissues. These proteins are members
      of the helix-loop-helix/Per-ARNT-SIM transcription factor family and form
      heterodimers with the aryl hydrocarbon receptor nuclear translocator. HIF-1 alpha
      can be activated by low oxygen concentrations and hypoxia-inducing agents. The
      AhR is activated by xenobiotica such as dioxins. Here, we analyze the
      interference between the AhR signaling, activated by 10 nM 2,3,7,8
      tetrachlorodibenzo- p-dioxin (TCDD), and the HIF-1 alpha pathway, induced by
      hypoxia (5% O2), in two human cell lines, the breast carcinoma cell line MCF-7
      and the hepatocyte cell line HepG2. In both cell lines, treatment with TCDD and
      hypoxia clearly reduced the stabilization of HIF-1 alpha and HRE-mediated
      promoter activity when compared to the induction under hypoxia alone. Because
      these effects were not observed after alpha-naphthoflavone treatment and HIF-1
      alpha mRNA was not down-regulated, HIF-1 alpha stabilization was revealed to be
      the target by TCDD in an AhR-depended mechanism. Under exposure to TCDD or
      hypoxia, the main regulator of HIF-1 alpha stability, the prolyl hydroxylase
      domain containing protein 2 (PHD2) showed an increase in promoter activity,
      transcript numbers, and protein amount. Therefore, PHD2 expression is regulated
      in an AhR-dependent manner under normoxia. The AhR-dependent regulation of PHD2
      under normoxia, however, is overwritten by the TCDD-mediated destabilization of
      HIF-1 alpha. The destabilization of HIF-1 alpha is the dominant effect causing
      the reduced PHD2 expression after simultaneous exposure to TCDD and hypoxia. We
      conclude that PHD2 does not mediate the TCDD-mediated HIF-1 alpha destabilization
      and does not control the interference of AhR and HIF-1 alpha pathways.

PMID- 18072752
TI  - Robotic hierarchical mixing for the production of combinatorial libraries of
      proteins and small molecules.
AB  - We present a method to automatically plan a robotic process to mix individual
      combinations of reactants in individual reaction vessels (vials or wells in a
      multiwell plate), mixing any number of reactants in any desired stoichiometry,
      and ordering the mixing steps according to an arbitrarily complex treelike
      assembly protocol. This process enables the combinatorial generation of complete
      or partial product libraries in individual reaction vessels from intermediates
      formed in the presence of different sets of reactants. It can produce either
      libraries of chimeric genes constructed by ligation of fragments from different
      parent genes or libraries of chemical compounds constructed by convergent
      synthesis. Given concentrations of the input reactants and desired amounts or
      volumes of the products, our algorithm, RoboMix, computes the required reactant
      volumes and the resulting product concentrations, along with volumes and
      concentrations for all intermediate combinations. It outputs a sequence of
      robotic liquid transfer steps that ensures that each combination is correctly
      mixed even when individualized stoichiometries are employed and with any
      fractional yield for a product. It can also account for waste in robotic liquid
      handling and residual volume needed to ensure accurate aspiration. We demonstrate
      the effectiveness of the method in a test mixing dyes with different UV-vis
      absorption spectra, verifying the desired combinations spectroscopically.

PMID- 18072753
TI  - High-throughput synthesis and screening of hydrogen-storage alloys.
AB  - Libraries of mixed-metal hydride materials are synthesized on a silicon
      microfabricated array of "hot-plate" MEMS devices, which allow high-throughput
      screening using temperature programmed desorption and infrared thermography. The
      heating plate of the MEMS device is a membrane with low heat capacity, allowing
      fast and localized temperature control and the extraction of calorimetric data
      from thermography. The combination of the synthetic method and screening chip
      allows a fast determination of the desorption temperature and hydrogen content of
      the materials. Mixed metal hydrides are synthesized directly. The potential of
      the method is exemplified by presenting results for the sorption properties of Mg
      xNi 1- x hydride thin-film materials. The results are consistent with the
      literature, showing the highest hydrogen capacity and desorption temperature for
      the MgH 2 phase in Mg-rich compositions and the promotion of a lower temperature
      desorption from the Mg 2NiH 4 phase, with a concomitant reduction in hydrogen
      capacity.

PMID- 18072754
TI  - Mechanistic investigation of beta-galactosidase-activated MR contrast agents.
AB  - We report a mechanistic investigation of an isomeric series of beta-galactosidase
      activated magnetic resonance contrast agents. Our strategy focuses on the
      synthesis of macrocyclic caged-complexes that coordinatively saturate a chelated
      lanthanide. Enzyme cleavage of the complex results in an open coordination site
      available for water that creates a detectable MR contrast agent. The complexes
      consist of a DO3A Gd(III) chelator modified with a galactopyranose at the N-10
      position of the macrocycle. We observed significant differences in relaxometric
      properties and coordination geometry that can be correlated to subtle variations
      of the linker between the macrocycle and the galactopyranose. After synthesis and
      purification of the R, S, and racemic mixtures of complexes 1 and 3 and
      measurement of the hydration number, water residence lifetime, and longitudinal
      relaxation rates, we propose mechanisms for water exclusion from the lanthanide
      in the precleavage state. While the stereochemistry of the linker does not
      influence the agents' properties, the mechanism of water exclusion for each
      isomer is significantly influenced by the position of modification. Data for one
      series with a methyl group substituted on the sugar-macrocycle linker at the
      alpha-position suggests a steric mechanism where the galactopyranose sugar blocks
      water from the Gd(III) center. In contrast, our observations for a second series
      with methyl substitution at the beta position of the sugar-macrocycle linker are
      consistent with a mechanism in which a bidentate anion occupies two available
      coordination sites of Gd(III) in the precleavage state.

PMID- 18072756
TI  - Role of Glu312 in binding and positioning of the substrate for the hydride
      transfer reaction in choline oxidase.
AB  - Choline oxidase catalyzes the oxidation of choline to glycine betaine, a
      compatible solute that accumulates in pathogenic bacteria and plants so they can
      withstand osmotic and temperature stresses. The crystal structure of choline
      oxidase was determined and refined to a resolution of 1.86 A with data collected
      at 100 K using synchrotron X-ray radiation. The structure reveals a covalent
      linkage between His99 Nepsilon2 and FAD C8M atoms, and a 123 A3 solvent-excluded
      cavity adjacent to the re face of the flavin. A hypothetical model for choline
      docked into the cavity suggests that several aromatic residues and Glu312 may
      orient the cationic substrate for efficient catalysis. The role of the negative
      charge on Glu312 was investigated by engineering variant enzymes in which Glu312
      was replaced with alanine, glutamine, or aspartate. The Glu312Ala enzyme was
      inactive. The Glu312Gln enzyme exhibited a Kd value for choline at least 500
      times larger than that of the wild-type enzyme. The Glu312Asp enzyme had a
      kcat/KO2 value similar to that of the wild-type enzyme but kcat and kcat/Km
      values that were 230 and 35 times lower, respectively, than in the wild-type
      enzyme. These data are consistent with the spatial location of the negative
      charge on residue 312 being important for the oxidation of the alcohol substrate.
      Solvent viscosity and substrate kinetic isotope effects suggest the presence of
      an internal equilibrium in the Glu312Asp enzyme prior to the hydride transfer
      reaction. Altogether, the crystallographic and mechanistic data suggest that
      Glu312 is important for binding and positioning of the substrate in the active
      site of choline oxidase.

PMID- 18072757
TI  - Dimers of boroglycine and methylamine boronic acid: a computational comparison of
      the relative importance of dative versus hydrogen bonding.
AB  - Boronic acids are widely used in materials science, pharmacology, and the
      synthesis of biologically active compounds. In this Article, geometrical
      structures and relative energies of dimers of boroglycine, H2N-CH2-B(OH)2, and
      its constitutional isomer H3C-NH-B(OH)2, were computed using second-order Moller
      Plesset perturbation theory and density functional theory; Dunning-Woon
      correlation-consistent cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis sets
      were employed for the MP2 calculations, and the Pople 6-311++G(d,p) basis set was
      employed for a majority of the DFT calculations. Effects of an aqueous
      environment were incorporated into the results using PCM and COSMO-RS
      methodology. The lowest-energy conformer of the H2N-CH2-B(OH)2 dimer was a six
      membered ring structure (chair conformation; Ci symmetry) with two intermolecular
      B:N dative-bonds; it was 14.0 kcal/mol lower in energy at the MP2/aug-cc-pVDZ
      computational level than a conformer with the classic eight-centered ring
      structure (Ci symmetry) in which the boroglycine monomers are linked by a pair of
      H-O...H bonds. Compared to the results of MP2 calculations with correlation
      consistent basis sets, DFT calculations using the PBE1PBE and TPSS functionals
      with the 6-311++G(d,p) basis set were significantly better at predicting relative
      conformational energies of the H2N-CH2-B(OH)2 and H3C-NH-B(OH)2 dimers than
      corresponding calculations using the BLYP, B3LYP, OLYP, and O3LYP functionals,
      particularly with respect to dative-bonded structures.

PMID- 18072758
TI  - Vapor-liquid equilibria simulation and an equation of state contribution for
      dipole-quadrupole interactions.
AB  - A systematic investigation on vapor-liquid equilibria (VLEs) of dipolar and
      quadrupolar fluids is carried out by molecular simulation to develop a new
      Helmholtz energy contribution for equations of state (EOSs). Twelve two-center
      Lennard-Jones plus point dipole and point quadrupole model fluids (2CLJDQ) are
      studied for different reduced dipolar moments micro*2=6 or 12, reduced
      quadrupolar moments Q*2=2 or 4 and reduced elongations L*=0, 0.505, or 1.
      Temperatures cover a wide range from about 55% to 95% of the critical temperature
      of each fluid. The NpT+test particle method is used for the calculation of vapor
      pressure, saturated densities, and saturated enthalpies. Critical data and the
      acentric factor are obtained from fits to the simulation data. On the basis of
      this data, an EOS contribution for the dipole-quadrupole cross-interactions of
      nonspherical molecules is developed. The expression is based on a third-order
      perturbation theory, and the model constants are adjusted to the present 2CLJDQ
      simulation results. When applied to mixtures, the model is found to be in
      excellent agreement with results from simulation and experiment. The new EOS
      contribution is also compatible with segment-based EOS, such as the various forms
      of the statistical associating fluid theory EOS.

PMID- 18072759
TI  - Theoretical study of the prohibited mechanism for ethylene/vinyl acetate co
      polymers to the wax crystal growth.
AB  - To understand the effect of pour point depressants (PPD) on the wax growth is
      important for designing PPD additives for use with different oils with high
      efficiency and good economics. In our current study, molecular mechanics,
      molecular dynamics, and quantum mechanics calculations were performed to
      investigate the prohibited mechanism of ethylene/vinyl acetate (EVA) additives on
      the paraffin deposition in oils. On the wax surface, a single C18 molecule and
      clusters were preferably deposited on the wax surface (010) in a parallel
      conformation, which resulted in the formation of large blocks of wax crystal. MD
      simulation indicated that the linear conformation of EVA was more favorable to be
      adsorbed onto the carbon backbone of the wax surface (010) with the polar
      fragments of vinyl acetate staying upside of the surface. Furthermore, four EVA
      molecules can efficiently optimize the inhibition effect for the deposition of
      the solute C18 molecules over 10x8 size wax surface (010). According to the
      simulation results, a simplified rational model was established to estimate the
      minimum dosage of EVA-type PPD for fuels with different paraffin contents. In a
      certain degree, this simplified model has provided an effective route to
      correlate microstructures and the properties of polymer-involving systems, which
      will shed light on the application of theoretical studies in industries.

PMID- 18072760
TI  - NMR studies of the Zn2+ interactions with rat and human beta-amyloid (1-28)
      peptides in water-micelle environment.
AB  - Alzheimer's disease is a fatal neurodegenerative disorder involving the abnormal
      accumulation and deposition of peptides (amyloid-beta, Abeta) derived from the
      amyloid precursor protein. Here, we present the structure and the Zn2+ binding
      sites of human and rat Abeta(1-28) fragments in water/sodium dodecyl sulfate
      (SDS) micelles by using 1H NMR spectroscopy. The chemical shift variations
      measured after Zn2+ addition at T>310 K allowed us to assign the binding donor
      atoms in both rat and human zinc complexes. The Asp-1 amine, His-6 Ndelta, Glu-11
      COO-, and His-13 Nepsilon of rat Abeta28 all enter the metal coordination sphere,
      while His-6 Ndelta, His-13, His-14 Nepsilon, Asp-1 amine, and/or Glu-11 COO- are
      all bound to Zn2+ in the case of human Abeta28. Finally, a comparison between the
      rat and human binding abilities was discussed.

PMID- 18072761
TI  - Molecular dynamics study of the stabilization of the silica hexamer Si6O15(6-) in
      aqueous and methanolic solutions.
AB  - We use molecular dynamics simulations to study the stabilization of the
      hexameric, cagelike silicate with double three-ring structure in aqueous and
      methanolic solutions. We find that in purely aqueous environments its
      stabilization requires the presence of both tetramethylammonium and
      tetraethylammonium (TEA) cations and involves the formation of a stable TMA layer
      which leads to a water-silicate heteronetwork clathrate. We also find that TEA
      alone can facilely stabilize the hexamer when methanol cosolvent is added, in
      accordance with experiment. The mechanism of this stabilization, however, differs
      from that in purely aqueous environments. Because of the unique properties of
      water-methanol mixtures, the organosilicate complex does not participate in
      heteronetwork clathrates but resides in a large solvent cavity; that is, it is
      forced out of true solution.

PMID- 18072751
TI  - Biological properties of single chemical-DNA adducts: a twenty year perspective.
AB  - The genome and its nucleotide precursor pool are under sustained attack by
      radiation, reactive oxygen and nitrogen species, chemical carcinogens, hydrolytic
      reactions, and certain drugs. As a result, a large and heterogeneous population
      of damaged nucleotides forms in all cells. Some of the lesions are repaired, but
      for those that remain, there can be serious biological consequences. For example,
      lesions that form in DNA can lead to altered gene expression, mutation, and
      death. This perspective examines systems developed over the past 20 years to
      study the biological properties of single DNA lesions.

PMID- 18072762
TI  - Epoxidation and 1,2-dihydroxylation of alkenes by a nonheme iron model system -
      DFT supports the mechanism proposed by experiment.
AB  - The FeII complexes of two isomeric pentadentate bispidine ligands in the presence
      of H2O2 are catalytically active for the epoxidation and 1,2-dihydroxylation of
      cyclooctene (bispidine = 3,7-diazabicyclo[3.3.1]nonane; the two isomeric
      pentadentate bispidine ligands discussed here have two tertiary amine and three
      pyridine donors). The published spectroscopic and mechanistic data, which include
      an extensive set of 18O labeling experiments, suggest that the FeIV=O complex is
      the catalytically active species, which produces epoxide as well as cis- and
      trans-1,2-dihydroxylated products. Several observations from the published
      experimental study are addressed with hybrid density functional methods and, in
      general, the calculations support the proposed, for nonheme iron model systems
      novel mechanism, where the formation of a radical intermediate emerges from the
      reaction of the FeIV=O oxidant and cyclooctene. The calculations suggest that the
      S = 1 ground state of the FeIV=O complex reacts with cyclooctene in a stepwise
      reaction, leading to the formation of a carbon-based radical intermediate. This
      radical is captured by O2 from air to produce the majority of the epoxide
      products in an aerobic atmosphere. Under anaerobic conditions, the produced
      epoxide product is due to the cyclization of the radical intermediate. Several
      possible spin states (ST = 3, 2, 1, 0) of the radical intermediate are close in
      energy. As a result of the substantial energy barrier, calculated for the ST = 3
      spin ground state, a spin-crossover during the cyclization step is assumed, and a
      possible two-state scenario is found, where the S = 2 state of the FeIV=O complex
      participates in the catalytic mechanism. The 1,2-dihydroxylation proceeds, as
      suggested by experiment, via an unprecedented pathway, where the radical
      intermediate is captured by a hydroxyl radical, the source of which is FeIII-OOH,
      and this reaction is barrierless. The calculations suggest that dihydroxylation
      can also occur by a direct oxidation pathway from FeIII-OOH. The strikingly
      different reactivities observed with the two isomeric bispidine FeII complexes
      are rationalized on the basis of structural and electronic differences.

PMID- 18072763
TI  - A systematic density functional study of the zero-field splitting in Mn(II)
      coordination compounds.
AB  - This work presents a detailed evaluation of the performance of density functional
      theory (DFT) for the prediction of zero-field splittings (ZFSs) in Mn(II)
      coordination complexes. Eighteen experimentally well characterized four-, five-,
      and six-coordinate complexes of the general formula [Mn(L)nL'2] with L' = Cl, Br,
      I, NCS, or N3 (L = an oligodentate ligand) are considered. Several DFT-based
      approaches for the prediction of the ZFSs are compared. For the estimation of the
      spin-orbit coupling (SOC) part of the ZFS, it was found that the Pederson-Khanna
      (PK) approach is more successful than the previously proposed quasi-restricted
      orbitals (QRO)-based method. In either case, accounting for the spin-spin (SS)
      interaction either with or without the inclusion of the spin-polarization effects
      improves the results. This argues for the physical necessity of accounting for
      this important contribution to the ZFS. On average, the SS contribution
      represents approximately 30% of the axial D parameters. In addition to the SS
      part, the SOC contributions of d-d spin flip (alphabeta) and ligand-to-metal
      charge transfer excited states (betabeta) were found to dominate the SOC part of
      the D parameter; the observed near cancellation between the alphaalpha and
      betaalpha parts is discussed in the framework of the PK model. The calculations
      systematically (correlation coefficient approximately 0.99) overestimate the
      experimental D values by approximately 60%. Comparison of the signs of calculated
      and measured D values shows that the signs of the calculated axial ZFS parameters
      are unreliable once E/D > 0.2. Finally, we find that the calculated D and E/D
      values are highly sensitive to small structural changes. It is observed that the
      use of theoretically optimized geometries leads to a significant deterioration of
      the theoretical predictions relative to the experimental geometries derived from
      X-ray diffraction. The standard deviation of the theoretical predictions for the
      D values almost doubles from approximately 0.1 to approximately 0.2 cm-1 upon
      using quantum chemically optimized structures. We do not find any noticeable
      improvement in considering basis sets larger than standard double- (SVP) or
      triple-zeta (TZVP) basis sets or using functionals other than the BP functional.

PMID- 18072764
TI  - Molybdenum oxo and imido complexes of beta-diketiminate ligands: synthesis and
      structural aspects.
AB  - Treatment of [MoO2(eta2-Pz)2] (Pz = 3,5-di-tert-butylpyrazolate) with the
      diketiminate ligand NacNacH (NacNac = CH[C(Me)NAr]2-, Ar = 2,6-Me2C6H3) at 55
      degrees C leads under reduction of the metal to the formation of the dimeric
      molybdenum(V) compound [{MoO2(NacNac)}2] (1). The compound was characterized by
      spectroscopic means and by X-ray crystal structure analysis. The dimer consists
      of a [Mo2O4]2+ core with a short Mo-Mo bond (2.5591(5) A) and one coordinated
      diketiminate ligand on each metal atom. The reaction of [MoO2(eta2-Pz)2] with
      NacNacH in benzene at room temperature leads to a mixture of 1 and the monomeric
      molybdenum(VI) compound [MoO2(NacNac)(eta2-Pz)] (2). From such solutions, yellow
      crystals of 2 suitable for X-ray structural analysis were obtained revealing the
      coordination of one bidentate NacNac and one eta2-coordinate Pz ligand. This
      renders the two oxo groups inequivalent. Further high oxidation state molybdenum
      compounds containing the NacNac ligand were obtained by the reaction of
      [Mo(NAr)2Cl2(dme)] (Ar = 2,6-Me2C6H3) and [Mo(N-t-Bu)2Cl2(dme)] (dme =
      dimethoxyethane) with 1 equiv of the potassium salt NacNacK forming
      [Mo(NAr)2Cl(NacNac)] (3) and [Mo(N-t-Bu)2Cl(NacNac)] (4), respectively, in good
      yields. The X-ray structure analysis of 3 revealed a penta-coordinate compound
      where the geometry is best described as trigonal-bipyramidal.

PMID- 18072765
TI  - Cobalt coordination induced functionalized molecular clefts: isolation of
      {Co(III)-Zn(II)} heterometallic complexes and their applications in Beckmann
      rearrangement reactions.
AB  - The present work shows that the Co3+ coordination to the deprotonated pyridine
      amide ligands orients the noncoordinated or hanging pyridine rings, thus
      furnishing a cleft in which Zn2+ ions coordinate. The building block approach
      points out a strategy to incorporate a Lewis acidic metal center in the
      periphery. This strategy has been used to synthesize Co3+-centered-Zn2+
      peripheral heterobimetallic complexes. These heterobimetallic complexes have been
      thoroughly characterized including structural studies and have been successfully
      shown to catalyze the Beckmann rearrangement of the aldoximes and ketoxime to
      their respective amides.

PMID- 18072766
TI  - Shorter argentophilic interaction than aurophilic interaction in a pair of
      dimeric {(NHC)MCl}(2) (M = Ag, Au) complexes supported over a N/O-functionalized
      N-heterocyclic carbene (NHC) ligand.
AB  - Synthesis, structure, bonding, and photoluminescence studies of a pair of neutral
      dimeric silver and gold complexes of a N/O-functionalized N-heterocyclic carbene
      ligand exhibiting closed-shell d10...d10 argentophilic and aurophilic
      interactions, are reported. In particular, dimeric complexes of the type {[1
      (benzyl)-3-(N-tert-butylacetamido)imidazol-2-ylidene]MCl}2 [M = Ag (2); Au (3)]
      displayed attractive metallophilic interaction in the form of a close ligand
      unsupported metal...metal contact [3.1970(12) A in 2; 3.2042(2) A in 3] as
      observed from X-ray diffraction study and also was further verified by low
      temperature photoluminescence study at 77 K that showed the characteristic
      emission [527 nm for 2; 529 nm for 3] owing to the metal...metal interaction. The
      nature of the metallophilic interaction in these complexes was further probed
      using computational studies that estimated the metal...metal interaction energy
      to be 12.8 (2) and 8.6 kcal/mol (3). Notably, the argentophilic interaction was
      found to be stronger than the aurophilic interaction in this series of neutral
      dimeric complexes. The complexes 2 and 3 were synthesized sequentially, with the
      silver 2 complex prepared by the reaction of the 1-(benzyl)-3-(N-tert
      butylacetamido)imidazolium chloride with Ag2O in 66% yield, while the gold 3
      complex was obtained by the transmetallation reaction of the silver 2 complex
      with (SMe2)AuCl in 86% yield.

PMID- 18072767
TI  - Specific RNA self-assembly with minimal paranemic motifs.
AB  - The paranemic crossover (PX) is a motif for assembling two nucleic acid molecules
      using Watson-Crick (WC) basepairing without unfolding preformed secondary
      structure in the individual molecules. Once formed, the paranemic assembly motif
      comprises adjacent parallel double helices that crossover at every possible point
      over the length of the motif. The interaction is reversible as it does not
      require denaturation of basepairs internal to each interacting molecular unit.
      Paranemic assembly has been demonstrated for DNA but not for RNA and only for
      motifs with four or more crossover points and lengths of five or more helical
      half-turns. Here we report the design of RNA molecules that paranemically
      assemble with the minimum number of two crossovers spanning the major groove to
      form paranemic motifs with a length of three half turns (3HT). Dissociation
      constants (Kd's) were measured for a series of molecules in which the number of
      basepairs between the crossover points was varied from five to eight basepairs.
      The paranemic 3HT complex with six basepairs (3HT_6M) was found to be the most
      stable with Kd = 1 x 10-8 M. The half-time for kinetic exchange of the 3HT_6M
      complex was determined to be approximately 100 min, from which we calculated
      association and dissociation rate constants ka = 5.11 x 103 M-1s-1 and kd = 5.11
      x 10-5 s-1. RNA paranemic assembly of 3HT and 5HT complexes is blocked by single
      base substitutions that disrupt individual intermolecular Watson-Crick basepairs
      and is restored by compensatory substitutions that restore those basepairs. The
      3HT motif appears suitable for specific, programmable, and reversible tecto-RNA
      self-assembly for constructing artificial RNA molecular machines.

PMID- 18072768
TI  - Rationally designed ligands that inhibit the aggregation of large gold
      nanoparticles in solution.
AB  - Hexadecanethiol (n-C16), 2,2-dimethylhexadecane-1-thiol (DMC16), and the
      multidentate thiol-based ligands 2-tetradecylpropane-1,3-dithiol (C16C2), 2
      methyl-2-tetradecylpropane-1,3-dithiol (C16C3), and 1,1,1
      tris(mercaptomethyl)pentadecane (t-C16) were evaluated for their ability to
      stabilize large gold nanoparticles (>15 nm) in organic solution. Citrate
      stabilized gold nanoparticles (20-50 nm) treated with the ligands were extracted
      from aqueous solution and dispersed into toluene. The degree of aggregation of
      the gold nanoparticles was monitored visually and further confirmed by UV-vis
      spectroscopy and dynamic light scattering (DLS). The bidentate ligands (C16C2 and
      C16C3) and particularly the tridentate ligand (t-C16) showed enhanced abilities
      to inhibit the aggregation of large gold nanoparticles in organic solution. For
      gold nanoparticles modified with these multidentate ligands, bound thiolate
      (S2p3/2 binding energy of 162 eV) was the predominant sulfur species (>85%) as
      evaluated by X-ray photoelectron spectroscopy (XPS). Although an entropy-based
      resistance to ordering of the loosely packed surfactant layers was initially
      considered to be a plausible mechanism for the enhanced stabilization afforded by
      the multidentate ligands, when taken as a whole, the data presented here support
      a model in which the enhanced stabilization arises largely (if not solely) from
      the multidentate chelate effect.

PMID- 18072769
TI  - Design of molecularly ordered framework of mesoporous silica with squared one
      dimensional channels.
AB  - Mesoporous silica with squared one-dimensional channels (KSW-2-type mesoporous
      silica), possessing a molecularly ordered framework arising from a starting
      layered polysilicate kanemite, was obtained through silylation of a surfactant
      (hexadecyltrimethylammonium, C16TMA)-containing mesostructured precursor with
      octoxytrichlorosilane (C8H17OSiCl3) and octylmethyldichlorosilane
      (C8H17(CH3)SiCl2). The presence of the molecular ordering in the silicate
      framework was confirmed by XRD and TEM. Octoxy groups grafted on KSW-2 can be
      eliminated by subsequent hydrolysis under very mild condition, and pure
      mesoporous silica was obtained with the retention of the kanemite-based
      framework. The framework is structurally stabilized by the attachment of
      additional SiO4 units to the framework, and the mesostructural ordering hardly
      changed under the presence of water vapor. A large number of silanol groups
      remained at the mesopore surfaces because C16TMA ions and octoxy groups can be
      removed without calcination. Octylmethylsilyl groups are regularly arranged at
      the mesopore surface due to the molecular ordering in the silicate framework. The
      molecularly ordered structural periodicity originating from kanemite is retained
      even after calcination at 550 degrees C, while that in the precursor without
      silylation disappeared. The synthetic strategy is quite useful for the design of
      the silicate framework of mesostructured and mesoporous materials with and
      without surface functional organic groups.

PMID- 18072770
TI  - Synthesis and magnetic investigation of ordered mesoporous two-line ferrihydrite.
AB  - We report here for the first time on the synthesis and characterization of
      ordered mesoporous two-line ferrihydrite. Ordered mesoporous ferrihydrite has
      been prepared via the nanocasting route. Two types of ordered mesoporous silica,
      two-dimensional hexagonal SBA-15 and three-dimensional cubic KIT-6, were employed
      as hard templates. The magnetic behavior of ferrihydrite replicas with an average
      diameter of about 7 nm was investigated by direct current magnetometry. The
      temperature dependence of magnetization shows a superparamagnetic transition
      around 70 K. Field-induced changes in the low-field behavior of the magnetization
      were observed below 30 K. The results are explained assuming a spin-glass-like
      state of the surface spins. The 2D hexagonal two-line ferrihydrite showed very
      large coercivity up to 1.6 kOe at 5 K.

PMID- 18072771
TI  - Ruthenium complexes with vinyl, styryl, and vinylpyrenyl ligands: a case of non
      innocence in organometallic chemistry.
AB  - We herein describe a systematic account of mononuclear ruthenium vinyl complexes
      L-{Ru}-CH=CH-R where the phosphine ligands at the (PR'3)2Ru(CO)Cl={Ru} moiety,
      the coordination number at the metal (L = 4-ethylisonicotinate or a vacant
      coordination site) and the substituent R (R = nbutyl, phenyl, 1-pyrenyl) have
      been varied. Structures of the enynyl complex Ru(CO)Cl(PPh3)2(eta1:eta2
      nBuHC=CHCCnBu), which results from the coupling of the hexenyl ligand of complex
      1a with another molecule of 1-hexyne, of the hexenyl complexes
      (nBuCH=CH)Ru(CO)Cl(PiPr3)2 (1c) and (nBuCH=CH)Ru(CO)Cl(PPh3)2(NC5H4COOEt-4) (1b),
      and of the pyrenyl complexes (1-Pyr-CH=CH)Ru(CO)Cl(PiPr3)2 (3c) and (1-Pyr
      CH=CH)Ru(CO)Cl(PPh3)3 (3a-P) have been established by X-ray crystallography. All
      vinyl complexes undergo a one-electron oxidation at fairly low potentials and a
      second oxidation at more positive potentials. Anodic half-wave or peak potentials
      show a progressive shift to lower values as pi-conjugation within the vinyl
      ligand increases. Carbonyl band shifts of the metal-bonded CO ligand upon
      monooxidation are significantly smaller than is expected of a metal-centered
      oxidation process and are further diminished as the vinyl CH=CH entity is
      incorporated into a more extended pi-system. ESR spectra of the electrogenerated
      radical cations display negligible g-value anisotropies and small deviations of
      the average g-value from that of the free electron. The vinyl ligands thus
      strongly contribute to or even dominate the anodic oxidation processes. This
      renders them a class of truly "non-innocent" ligands in organometallic ruthenium
      chemistry. Experimental findings are fully supported by quantum chemical
      calculations: The contribution of the vinyl ligand to the HOMO increases from 46%
      (Ru-vinyl delocalized) to 84% (vinyl dominated) as R changes from nbutyl to 1
      pyrenyl.

PMID- 18072772
TI  - Effect of ortho-SR groups on O-H bond strength and H-atom donating ability of
      phenols: a possible role for the Tyr-Cys link in galactose oxidase active site?
AB  - Rotation about the Ar-S bond in ortho-(alkylthio)phenols strongly affects the
      bond dissociation enthalpy (BDE) and the reactivity of the OH group. Newly
      synthesized sulfur containing heterocycles 3 and 4, where the -SR group is almost
      coplanar with the phenolic ring, are characterized by unusually low BDE(O-H)
      values (79.6 and 79.2 kcal/mol, respectively) and by much higher reactivities
      toward peroxyl radicals than the ortho-methylthio derivative 1 (82.0 kcal/mol).
      The importance of the intramolecular hydrogen bond (IHB) in determining the BDE(O
      H) was demonstrated by FT-IR experiments, which showed that in heterocycles 3 and
      4 the IHB between the phenolic OH group and the S atom is much weaker than that
      present in 1. Since the IHB can be formed only if the -SR group adopts an out-of
      plane geometry, this interaction is possible only in the methylthio derivative 1
      and not in 3 and 4. The additive contribution to the phenolic BDE(O-H) of the -SR
      substituent therefore varies from -3.1 to +2.8 kcal/mol for the in-plane and out
      of-plane conformations, respectively. These results may be relevant to
      understanding the role of the tyrosine-cysteine link in the active site of
      galactose oxidase, an important enzyme that catalyzes the two-electron aerobic
      oxidation of primary alcohols to aldehydes. The switching of the ortho -SR
      substituent between perpendicular and planar conformations may account for the
      catalytic efficiency of this enzyme.

PMID- 18072773
TI  - Size-dependent charge collection in junctions containing single-size and multi
      size arrays of colloidal CdSe quantum dots.
AB  - This paper describes the electrical characteristics of junctions composed of
      three-dimensional arrays of colloidal CdSe quantum dots (QDs) with tin-doped
      indium oxide (ITO)/poly(3,4-ethylenedioxy-thiophene):poly(styrenesulfonate)
      (PEDOT:PSS) and eutectic Ga-In (EGaIn) electrodes. It focuses on a comparison of
      junctions containing QDs of one size to those of arrays containing QDs of
      multiple sizes. This comparison makes it possible to estimate the relative
      contributions of transport across various interfaces (e.g., between the QDs and
      between the QDs and the electrodes) to the observed electrical characteristics of
      the junction and to evaluate the dependence of these contributions on the
      locations of various sizes of QDs within the junction. The junctions were diodes,
      and their turn-on voltage depended on the size of the QDs next to the PEDOT:PSS.
      We describe this dependence using a Marcus model to estimate the barrier for
      charge transfer induced by the difference in energies between the orbitals of the
      QDs and the valence band of PEDOT:PSS.

PMID- 18072774
TI  - The use of size-selective excitation to study photocurrent through junctions
      containing single-size and multi-size arrays of colloidal CdSe quantum dots.
AB  - This paper describes a study of the generation and flow of photocurrent through
      junctions containing three-dimensional arrays of colloidal CdSe quantum dots
      (QDs) of either a single size or multiple sizes. The electrodes were indium tin
      oxide (ITO) covered with a thin layer of poly(3,4-ethylenedioxy
      thiophene):poly(styrenesulfonate) (PEDOT:PSS) and a eutectic alloy of Ga and In
      (EGaIn). We measured the current-voltage characteristics of the junctions in the
      dark and under illumination, with various sources and wavelengths of excitation,
      and their photocurrent action spectra. Size-selective photoexcitation of the
      arrays of multiple sizes of QDs helped to determine (i) the location of the
      interface at which photoinduced separation of charge occurred, (ii) whether the
      energy absorbed by the QDs was redistributed before separation of charge, and
      (iii) the dependence of the photovoltage on the locations of various sizes of QDs
      within the junction. This research is a step toward the use of QDs for harvesting
      light and for transporting energy and charge in devices-for example, solar cells
      and photodetectors-that operate at zero bias.

PMID- 18072775
TI  - Toward a synthetically useful stereoselective C-H amination of hydrocarbons.
AB  - Reaction between a sulfur(VI) compound and an iodine(III) oxidant in the presence
      of a catalytic quantity (<=3 mol %) of a rhodium(II) catalyst leads to the
      formation of a chiral metallanitrene of unprecedented reactivity. The latter
      allows intermolecular C-H amination to proceed in very high yields up to 92% and
      excellent diastereoselectivities up to 99% with C-H bond containing starting
      materials as the limiting component. The scope of this C-H functionalization
      includes benzylic and allylic substrates as well as alkanes. Secondary positions
      react preferentially, but insertion into activated primary C-H bonds or
      sterically accessible tertiary sites is also possible. Cooperative effects
      between the nitrene precursor and the chiral catalyst at the origin of these good
      results have also been applied to kinetic resolution of racemic sulfonimidamide.
      This methodology paves the way to the use of Csp3-H bonds as synthetic precursors
      for the introduction of a nitrogen functionality into selected positions.

PMID- 18072776
TI  - Dipolar chemical shift correlation spectroscopy for homonuclear carbon distance
      measurements in proteins in the solid state: application to structure
      determination and refinement.
AB  - High-resolution solid-state NMR spectroscopy has become a promising tool for
      protein structure determination. Here, we describe a new dipolar-chemical shift
      correlation experiment for the measurement of homonuclear 13C-13C distances in
      uniformly 13C,15N-labeled proteins and demonstrate its suitability for protein
      structure determination and refinement. The experiments were carried out on the
      beta1 immunoglobulin binding domain of protein G (GB1). Both intraresidue and
      interresidue distances between carbonyl atoms and atoms in the aliphatic side
      chains were collected using a three-dimensional chemical shift correlation
      spectroscopy experiment that uses homogeneously broadened rotational resonance
      recoupling for carbon mixing. A steady-state approximation for the polarization
      transfer function was employed in data analysis, and a total of 100
      intramolecular distances were determined, all in the range 2.5-5.5 A. An
      additional 41 dipolar contacts were detected, but the corresponding distances
      could not be accurately quantified. Additional distance and torsional restraints
      were derived from the proton-driven spin diffusion measurements and from the
      chemical shift analysis, respectively. Using all these restraints, it was
      possible to refine the structure of GB1 to a root-mean square deviation of 0.8 A.
      The approach is of general applicability for peptides and small proteins and can
      be easily incorporated into a structure determination and refinement protocol.

PMID- 18072777
TI  - Two-dimensional supramolecular nanopatterns formed by the coadsorption of guanine
      and uracil at the liquid/solid interface.
AB  - A novel supramolecular nanostructure formed by the coadsorption of the
      complementary nucleobases guanine (G) and uracil (U) at the liquid (1-octanol
      solvent)/solid (graphite) interface is revealed by scanning tunneling microscopy
      (STM). The GU supramolecular structure is distinctly different from the
      structures observed by STM when the individual nucleobases (NB) are adsorbed on
      graphite in the control experiments. Using a systematic methodology and ab initio
      density functional theory (DFT), an atomistic structural model is proposed for
      the supramolecular coadsorbed GU structure, which consists of a periodic
      repetition of cyclic units based on the strongest GU base pairing.

PMID- 18072778
TI  - Tunable aptamer capillary electrophoresis and its application to protein
      analysis.
AB  - A tunable aptamer electrophoretic assay enables highly sensitive fluorescence
      detection of multiple proteins and protein isomers. The electrophoretic mobility
      of proteins is tuned with DNA aptamers binding to the target proteins.
      Fluorescently labeled aptamers of varying nucleotide lengths serve as both charge
      modulators for capillary electrophoresis separation and as fluorescent affinity
      probes for ultrasensitive laser-induced fluorescence detection. Simultaneous
      determination of pM levels of human immunodeficiency virus reverse transcriptase,
      thrombin, human immunoglobulin E, and two isomers of platelet-derived growth
      factor in dilute human serum demonstrates the potential applications of this
      assay to biomarker development.

PMID- 18072779
TI  - Redirecting the cyclization steps of fungal polyketide synthase.
AB  - Regiospecific cyclizations of the nascent poly-beta-ketone backbones dictate the
      structures of polyketide natural products. The fungal iterative megasynthases use
      terminal thioesterase/claisen cyclase (TE/CLC) domains to direct the fate of the
      polyketide chains. In this work, we present two strategies toward redirecting the
      cyclization steps of fungal PKSs using the Gibberella fujikuroi PKS4. First,
      inactivation or removal of the TE/CLC domain resulted in the synthesis of the new
      polyketide SMA93 2. Complementation of the mutant PKS4 with a standalone TE/CLC
      domain restored the regioselective cyclization steps of PKS4 and led to the
      synthesis of SMA76 1, demonstrating that cyclization enzymes can interact with
      the megasynthase in trans. This led to the second approach in which various
      dissociated, bacterial tailoring enzymes were added to the megasynthase in trans.
      Addition of the act KR led to the synthesis of mutactin 3, while the addition of
      first ring and second ring cyclases yielded anthraquinone compounds DMAC 5 and
      SEK26 6. The cooperative activities of fungal and bacterial PKS components are
      especially important and enable synthesis of polyketides utilizing enzymes from
      two distinct families of PKSs.

PMID- 18072780
TI  - Stepwise self-assembly of DNA tile lattices using dsDNA bridges.
AB  - The simple helical motif of double-strand DNA (dsDNA) has typically been judged
      to be uninteresting for assembly in DNA-based nanotechnology applications. In
      this letter, we demonstrate construction of superstructures consisting of
      heterogeneous DNA motifs using dsDNA in conjunction with more complex, cross-tile
      building blocks. Incorporation of dsDNA bridges in stepwise assembly processes
      can be used for controlling length and directionality of superstructures and is
      analogous to the "reprogramming" of sticky-ends displayed on the DNA tiles. Two
      distinct self-assembled DNA lattices, fixed-size nanoarrays, and extended 2D
      crystals of nanotracks with nanobridges, are constructed and visualized by high
      resolution, liquid-phase atomic force microscopy.

PMID- 18072781
TI  - Aligned carbon nanotube/polymer composite films with robust flexibility, high
      transparency, and excellent conductivity.
AB  - This work reports a novel and general synthesis of aligned carbon
      nanotube/polymer composite films with high optical transparency, robust
      flexibility, and excellent conductivity. These composite films show many
      potential applications such as flexible conductors for optoelectronic devices.

PMID- 18072782
TI  - Inherent photoluminescence properties of poly(propyl ether imine) dendrimers.
AB  - Hydroxyl group terminated poly(propyl ether imine) dendrimers of 1 to 5
      generations absorb in the region of 260-340 nm, in MeOH and aqueous solutions.
      Excitation of a solution of the dendrimers at 330 nm led to an emission at
      approximately 390 nm. The emission intensities increased under acidic pH and in
      more viscous solvents. The presence of air did not affect the emission profiles,
      as also aging of a dendrimer solution for prolonged periods. Lifetime
      measurements show at least two species responsible for the emission. Anions
      perchlorate, periodate, nitrite, and pyridinium methyliodide quenched the
      fluorescence efficiently, among several anions tested.

PMID- 18072783
TI  - Oxidative coupling of arylboronic acids with arenes via Rh-catalyzed direct C-H
      arylation.
AB  - Oxidative coupling of three different arenes and a thiophene derivative with
      various arylboronic acids was achieved with a [RhCl(C2H4)2]2/P[p-(CF3)C6H4]3
      catalyst system. Commercially available 2,2,6,6-tetramethylpiperidine-N-oxyl
      radical (TEMPO) was used as a stoichiometric oxidant. A 2-pyridyl group and an
      imine functional group served as ortho-directing groups to mediate the direct C-H
      arylation by a Rh complex. Moderate to excellent yields were obtained for the
      coupling reactions.

PMID- 18072784
TI  - Indium(III) acetate-catalyzed intermolecular radical addition of organic iodides
      to electron-deficient alkenes.
AB  - In the presence of phenylsilane and a catalytic amount of indium(III) acetate,
      organic iodides added to electron-deficient alkenes in ethanol at room
      temperature. Both simple and functionalized organic iodides were applicable to
      this reaction. A plausible reaction mechanism involves the formation of indium
      hydride species by hydride transfer from silicon to indium and an indium hydride
      mediated radical chain process.

PMID- 18072785
TI  - Biomimetic synthesis of the shimalactones.
AB  - A biomimetic synthesis of shimalactone A and B is described. Its key features are
      an unprecedented acid-catalyzed cyclization of a dienyl beta-ketolactone and a
      Stille coupling/8pi-6pi electrocyclization cascade to create the
      oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene, respectively. The synthesis
      is convergent and void of protecting groups.

PMID- 18072786
TI  - Quantification of the (anti)aromaticity of fulvalenes subjected to pi-electron
      cross-delocalization.
AB  - Fulvalenes 3-12 were theoretically studied at the ab initio level of theory. For
      the global minima structures, the occupation of the bonding (pi)C=C orbital of
      the interring C=C double bond obtained by NBO analysis quantitatively proves pi
      electron cross-delocalization resulting in, at least partially, 2- or 6pi
      electron aromaticity and 8pi-electron antiaromaticity for appropriate moieties.
      The cross-conjugation was quantified by the corresponding occupation numbers and
      lengths of the interring C=C double bonds, while the aromaticity or
      antiaromaticity due to cross-delocalization of the pi-electrons was visualized
      and quantified by through-space NMR shielding surfaces.

PMID- 18072787
TI  - Rhodium fluorapatite catalyst for the synthesis of trisubstituted olefins via
      cross coupling of Baylis-Hillman adducts and arylboronic acids.
AB  - Treatment of fluorapatite (prepared by incorporating basic species F(-) in
      apatite in situ by coprecipitation) with an aqueous solution of RhCl(3) resulted
      in rhodium-exchanged fluorapatite catalyst (RhFAP), which successfully promoted
      cross coupling of Baylis-Hillman adducts with arylboronic acids to yield
      trisubstituted olefins. A variety of arylboronic acids and Baylis-Hillman adducts
      were converted to the corresponding trisubstituted olefins, demonstrating the
      versatility of the reaction. The reaction is highly stereoselective. RhFAP was
      recovered quantitatively by simple filtration and reused with almost consistent
      activity.

PMID- 18072789
TI  - Oxa-ene reaction of enols of amides with 4-phenyl-1,2,4-triazoline-3,5-dione.
AB  - The reaction of 16 enols of amides with 4-phenyl-1,2,4-triazoline-1,3-dione gave
      open chain adducts rather than the [2 + 2] cycloadducts with a hemiaminal moiety,
      both in solid state and in solution. This assignment is based on X-ray
      crystallography, (1)H and (13)C NMR data, and IR spectra. The suggested mechanism
      involves hydroxyl proton loss in a formal oxa-ene reaction. Mechanistic details
      and a possible alternative are discussed.

PMID- 18072788
TI  - Optically switchable chelates: optical control and sensing of metal ions.
AB  - This study introduces new concepts in the design, synthesis, and in vitro and in
      vivo characterization, manipulation, and imaging of organic chelates whose
      association with metal ions is rapidly and reversibly controlled by using light.
      Di- and tricarboxylic group bearing photochromes, nitrobenzospiropyran
      (nitroBIPS), undergo rapid and reversible, optically driven transitions between
      their spiro (SP) and fluorescent merocyanine (MC) states. The MC state of
      nitroBIPS-8-DA binds tightly to various metal ions resulting in specific shifts
      in absorption and fluorescence, and the dissociation constant for its Gadolinium
      complex in water is measured at approximately 5 microM. The metal-bound MC state
      is converted to the weaker-binding SP state with use of 543 nm light, while the
      SP to MC transition is complete with use of 365 or 720 nm (2-photon) light within
      several microseconds. Fluorescence imaging of the MC state of nitroBIPS-8-TriA
      was used to quantify the rate and efficiency of optical switching and to provide
      a real-time readout of the state of the optically switchable chelate within
      living cells.

PMID- 18072790
TI  - Bis(heterocumulenes) derived from the 1,4-diphenyl-1,3-butadiyne framework.
      Synthesis of three new classes of axially chiral biheteroaryls.
AB  - Bis(ketenimines) and bis(carbodiimides) derived from 1,4-bis(2-aminophenyl)-1,3
      butadiynes via two independent biradical cyclizations provided, respectively,
      axially chiral bis(benzocarbazoles) and bis(quinindolines). Mixed biheteroaryls,
      consisting of benzocarbazole and quinindoline units, have been also prepared by a
      slightly modified strategy.

PMID- 18072792
TI  - Thermal properties of the gel made by low molecular weight gelator 1,2-O-(1
      ethylpropylidene)-alpha-D-glucofuranose with toluene and molecular dynamics of
      solvent.
AB  - The studies of the gel-to-sol phase transition by the Raman, FT-IR, and 1H NMR
      methods of the gel made by low molecular weight organogelator 1,2-O-(1
      ethylpropylidene)-alpha-D-glucofuranose with toluene as the solvent are reported.
      The FT-IR spectra revealed the existence of a hydrogen bond network formed by
      gelator molecules in the crystalline and gel phase. In both phases, the network
      formation is dominated by the gelator self-interaction. Upon gelation, only one
      stretching band of infrared absorption modes nualpha, assigned to the O(6)H
      hydroxyl protons of gelator, is shifted by Deltaupsilonalpha = 25 cm-1, which
      indicates the involvement of this proton in the interaction with the solvent
      molecules. The phase transition measurements performed as a function of gelator
      concentration allowed the calculation of the energy correlated with the
      transition from gel to solution phase. The obtained value of 72 kJ/mol is the
      largest one reported up until now for monosaccharide-based gels. The analysis of
      the temperature measurements of the toluene 1H NMR spectra provides evidence for
      a different chemical environment of toluene molecules in the gel. The toluene
      spin-lattice relaxation in bulk and gel indicate that the viscosity is most
      likely the main factor that influences the dynamics of toluene.

PMID- 18072791
TI  - Characterization of insulin adsorption in the presence of albumin by time-of
      flight secondary ion mass spectrometry and X-ray photoelectron spectroscopy.
AB  - With a view to develop an encapsulation membrane for a bioartificial pancreas, we
      have studied the adsorption of insulin and human serum albumin (HSA) on it. The
      aim of this study was to determine the possibility of insulin detection on a
      polycarbonate membrane surface in the presence of HSA, an abundant blood protein.
      The first step of the work consisted in the identification of time-of-flight
      secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy
      (XPS) specific signals for insulin and albumin. For this purpose, adsorption
      isotherms in physiological conditions (pH = 7.2, T = 37 degrees ) were
      established for the two proteins by looking at the SIMS intensity variations of
      the characteristic protein and substrate fragments when increasing the protein
      concentration in the solution. The CHS+ ToF-SIMS fragment and the S2p XPS peak
      were identified as representative insulin signals. The second step of the work
      consisted in performing simultaneous adsorption of the two proteins with
      increasing insulin concentration. We observed an increase of the insulin signal
      in ToF-SIMS and XPS for insulin concentration beyond 5 microg/mL. Principal
      component analysis (PCA) of the ToF-SIMS results permits us to obtain information
      about the protein layer composition. The results show that at low relative
      insulin concentration in solution, the mixed adsorbed layers are enriched in
      insulin compared to the solution.

PMID- 18072793
TI  - Adsorption of poly(amido amine) (PAMAM) dendrimers on silica: importance of
      electrostatic three-body attraction.
AB  - Adsorption of poly(amido amine) (PAMAM) dendrimers to silicon oxide surfaces was
      studied as a function of pH, ionic strength, and dendrimer generation. By
      combining optical reflectometry and atomic force microscopy (AFM), the adsorbed
      layers can be fully characterized and an unequivocal determination of the
      adsorbed mass becomes possible. For early stages, the adsorption process is
      transport limited and of first order with respect to the dendrimer solution
      concentration. For later stages, the surface saturates and the adsorbed
      dendrimers form loose but correlated liquidlike surface structures. This
      correlation is evidenced by a peak in the pair correlation function determined by
      AFM. The maximum adsorbed amount increases with increasing ionic strength and pH.
      The increase with the ionic strength is explained by the random sequential
      adsorption (RSA) model and electrostatic repulsion between the dendrimers. The
      adsorbing dendrimers interact by the repulsive screened Coulomb potential, whose
      range decreases with increasing ionic strength and thus leads to increasing
      adsorbed densities. The pH increase is interpreted as an effect of the substrate
      and is quantitatively explained by the extended three-body RSA model. This model
      stipulates the importance of a three-body interaction acting between two
      adsorbing dendrimers and the charged substrate. The presence of the charged
      substrate weakens the repulsion between the adsorbing dendrimers and thus leads
      to higher surface densities. This effect can be interpreted as an additional
      attractive three-body interaction, which acts in addition to the usual two-body
      repulsion and originates from the additional screening of the Coulomb repulsion
      by the counterions accumulating in the diffuse layer.

PMID- 18072794
TI  - Patterned nonadhesive surfaces: superhydrophobicity and wetting regime
      transitions.
AB  - Nonadhesive and water-repellent surfaces are required for many tribological
      applications. We study mechanisms of wetting of patterned superhydrophobic Si
      surfaces, including the transition between various wetting regimes during
      microdroplet evaporation in environmental scanning electron microscopy (ESEM) and
      for contact angle and contact angle hysteresis measurements. Wetting involves
      interactions at different scale levels: macroscale (water droplet size),
      microscale (surface texture size), and nanoscale (molecular size). We propose a
      generalized formulation of the Wenzel and Cassie equations that is consistent
      with the broad range of experimental data. We show that the contact angle
      hysteresis involves two different mechanisms and how the transition from the
      metastable partially wetted (Cassie) state to the homogeneously wetted (Wenzel)
      state depends upon droplet size and surface pattern parameters.

PMID- 18072795
TI  - Curvature coupling dependence of membrane protein diffusion coefficients.
AB  - We consider the lateral diffusion of a protein interacting with the curvature of
      the membrane. The interaction energy is minimized if the particle is at a
      membrane position with a certain curvature that agrees with the spontaneous
      curvature of the particle. We employ stochastic simulations that take into
      account both the thermal fluctuations of the membrane and the diffusive behavior
      of the particle. In this study, we neglect the influence of the particle on the
      membrane dynamics, thus the membrane dynamics agrees with that of a freely
      fluctuating membrane. Overall, we find that this curvature coupling substantially
      enhances the diffusion coefficient. We compare the ratio of the projected or
      measured diffusion coefficient and the free intramembrane diffusion coefficient,
      which is a parameter of the simulations, with analytical results that rely on
      several approximations. We find that the simulations always lead to a somewhat
      smaller diffusion coefficient than that from our analytical approach. A detailed
      study of the correlations of the forces acting on the particle indicates that the
      diffusing inclusion tries to follow favorable positions on the membrane such that
      forces along the trajectory are on average smaller than they would be for random
      particle positions.

PMID- 18072796
TI  - A novel drug carrier: lipophilic drug-loaded polyglutamate/polyelectrolyte
      nanocontainers.
AB  - A novel lipophilic drug carrier, "oil-in-water" multifunctional composite
      nanocontainers, is developed by combining ultrasonic technique and layer-by-layer
      assembly. Polyglutamate/polyethyleneimine/poly(acrylic acid) nanocontainers
      loaded with the lipophilic drug, rifampicin, dissolved in soybean oil were
      fabricated. Raman confocal microscopy and scanning electron microscopy proved the
      successful incorporation of rifampicin into composite water-dispersible
      polyglutamate/polyelectrolyte nanocontainers. Transmission electron microscopy
      and confocal laser scanning microscopy indicated that the drug can be released by
      changing the pH value of the media due to the pH-responsive properties of the
      polyglutamate/polyelectrolyte shell.

PMID- 18072797
TI  - Odd-even effects in self-assembled monolayers of omega-(biphenyl-4
      yl)alkanethiols: a first-principles study.
AB  - Conjugated molecules with a saturated alkyl linker between a thiol docking group
      and the pi-conjugated core have been shown to form self-assembled monolayers
      (SAMs) with a high degree of long-range order and uniformity. Additionally,
      pronounced odd-even effects have been observed in a number of properties
      characterizing these SAMs. We focus on omega-(biphenyl-4-yl)alkanethiols with n =
      0-6 -(CH2)n- units deposited on Au(111) and investigate the microscopic origin of
      these odd-even effects in terms of the local sulfur-gold bonding geometry by
      employing first-principles calculations. An additional structural parameter, the
      torsion angle between the two phenyl rings in the biphenyl moiety, is identified
      and its relation to the experimentally observed odd-even effects is discussed.
      More importantly, we address relevant quantities for the application of these
      SAMs in molecular electronic devices, in particular, the modification of the work
      function of the underlying metal substrate and the energetic alignment of the
      molecular orbitals in the SAM with the Fermi level. While no clear trend emerges
      for the former, we find pronounced odd-even effects for the latter. Furthermore,
      the insertion of a single methylene unit between the biphenyl core and the thiol
      appears to largely decouple the valence electronic systems of the pi-conjugated
      segment and the gold substrate. Our results thus provide a solid theoretical
      basis for the interface energetics in this important class of systems.

PMID- 18072798
TI  - Molecular scale buckling mechanics in individual aligned single-wall carbon
      nanotubes on elastomeric substrates.
AB  - We have studied the scaling of controlled nonlinear buckling processes in
      materials with dimensions in the molecular range (i.e., approximately 1 nm)
      through experimental and theoretical studies of buckling in individual single
      wall carbon nanotubes on substrates of poly(dimethylsiloxane). The results show
      not only the ability to create and manipulate patterns of buckling at these
      molecular scales, but also, that analytical continuum mechanics theory can
      explain, quantitatively, all measurable aspects of this system. Inverse
      calculation applied to measurements of diameter-dependent buckling wavelengths
      yields accurate values of the Young's moduli of individual SWNTs. As an example
      of the value of this system beyond its use in this type of molecular scale
      metrology, we implement parallel arrays of buckled SWNTs as a class of
      mechanically stretchable conductor.

PMID- 18072799
TI  - Mesoporous Co3O4 nanowire arrays for lithium ion batteries with high capacity and
      rate capability.
AB  - We report the high capacity and rate capability of mesoporous Co3O4 nanowire (NW)
      arrays as anodes in Li ion batteries. At a current of 1C, the NW arrays maintain
      a capacity of 700 mAh/g after 20 discharge/charge cycles. When the current is
      increased to 50C, 50% of the capacity can be retained. With their ease of large
      area synthesis and superior electrochemical properties, these Co3O4 NW arrays
      will be interesting for practical Li ion batteries.

PMID- 18072800
TI  - Single-step coating of mesoporous silica on cetyltrimethyl ammonium bromide
      capped nanoparticles.
AB  - A generalized, single-step synthesis procedure to coat individual cetyltrimethyl
      ammonium bromide- (CTAB) capped nanoparticles with a thin layer of mesoporous
      silica is outlined. This coating method was demonstrated on CTAB-capped Au
      nanorods and CTAB-transferred CdSe/ZnS quantum dots with silica coatings
      approximately 15 nm thick containing pores approximately 4 nm in diameter. This
      porous silica coating can serve as a platform for further surface modification to
      facilitate the rapid translation of nanoparticles to a wide range of end
      applications.

PMID- 18072802
TI  - Iminium catalysis.

PMID- 18072803
TI  - Asymmetric enamine catalysis.

PMID- 18072804
TI  - Chiral dialkylaminopyridine catalysts in asymmetric synthesis.

PMID- 18072805
TI  - Recent developments in the use of catalytic asymmetric ammonium enolates in
      chemical synthesis.

PMID- 18072806
TI  - Recent development and application of chiral phase-transfer catalysts.

PMID- 18072807
TI  - Stereoselective anhydride openings.

PMID- 18072808
TI  - Small-molecule H-bond donors in asymmetric catalysis.

PMID- 18072809
TI  - Asymmetric catalysis mediated by synthetic peptides.

PMID- 18072810
TI  - Chalcogenides as organocatalysts.

PMID- 18072811
TI  - The role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in
      Alzheimer's disease: therapeutic implications.
AB  - Alzheimer's disease is a complex neurodegenerative disorder, with aging, genetic
      and environmental factors contributing to its development and progression. The
      complexity of Alzheimer's disease presents substantial challenges for the
      development of new therapeutic agents. Alzheimer's disease is typified by
      pathological depositions of beta-amyloid peptides and neurofibrillary tangles
      within the diseased brain. It has also been demonstrated to be associated with a
      significant microglia-mediated inflammatory component, dysregulated lipid
      homeostasis and regional deficits in glucose metabolism within the brain. The
      peroxisome proliferator-activated receptor-gamma (PPARgamma) is a prototypical
      ligand-activated nuclear receptor that coordinates lipid, glucose and energy
      metabolism, and is found in elevated levels in the brains of individuals with
      Alzheimer's disease. A recently appreciated physiological function of this type
      of receptor is its ability to modulate inflammatory responses. In animal models
      of Alzheimer's disease, PPARgamma agonist treatment results in the reduction of
      amyloid plaque burden, reduced inflammation and reversal of disease-related
      behavioural impairment. In a recent phase II clinical trial, the use of the
      PPARgamma agonist rosiglitazone was associated with improved cognition and memory
      in patients with mild to moderate Alzheimer's disease. Thus, PPARgamma may act to
      modulate multiple pathophysiological mechanisms that contribute to Alzheimer's
      disease, and represents an attractive therapeutic target for the treatment of the
      disease.

PMID- 18072812
TI  - Neurobiological and clinical effects of the antidepressant tianeptine.
AB  - The precise neurobiological processes involved in depression are not clear, but
      it is recognized that numerous factors are involved, including changes in
      neurotransmitter systems and brain plasticity. Neuroplasticity refers to the
      ability of the brain to adapt functionally and structurally to stimuli.
      Impairment of neuroplasticity in the hippocampus, amygdala and cortex is
      hypothesized to be the mechanism by which cognitive function, learning, memory
      and emotions are altered in depression. The mechanisms underlying alterations in
      neuroplasticity are believed to relate to changes in neurotransmitters, hormones
      and growth factors. Structural changes in the hippocampus that have been proposed
      to be associated with depression include dendritic atrophy, reduced levels of
      cerebral metabolites, decreased adult neurogenesis (generation of new nerve
      cells) and reduced volume. Increased dendritic branching occurs in the
      basolateral nucleus of the amygdala. Reduced neuronal size and glial cell density
      occur in the prefrontal cortex. Clinically, tianeptine is an antidepressant
      effective in reducing symptoms of depression in mild to moderate-to-severe major
      depression, including over the long term. Tianeptine is also effective in
      alleviating the symptoms of depression-associated anxiety. It is generally well
      tolerated, with little sedation or cognitive impairment. The efficacy profile of
      tianeptine could be explained by its neurobiological properties observed in
      animal models. Tianeptine prevents or reverses stress-associated structural and
      cellular changes in the brain and normalizes disrupted glutamatergic
      neurotransmission. In particular, in the hippocampus, it prevents stress-induced
      dendritic atrophy, improves neurogenesis, reduces apoptosis and normalizes
      metabolite levels and hippocampal volume. Tianeptine also has beneficial effects
      in the amygdala and cortex and can reverse the effects of stress on neuronal and
      synaptic functioning. The neurobiological properties of tianeptine may provide an
      explanation not only for its antidepressant activity, but also for its anxiolytic
      effects in depressed patients and its lack of adverse effects on cognitive
      function and memory.

PMID- 18072813
TI  - Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of
      action and clinical efficacy.
AB  - Antiepileptic drugs (AEDs) are used extensively to treat multiple non-epilepsy
      disorders, both in neurology and psychiatry. This article provides a review of
      the clinical efficacy of AEDs in non-epilepsy disorders based on recently
      published preclinical and clinical studies, and attempts to relate this efficacy
      to the mechanism of action of AEDs and pathophysiological processes associated
      with the disorders. Some newer indications for AEDs have been established, while
      others are under investigation. The disorders where AEDs have been demonstrated
      to be of clinical importance include neurological disorders, such as essential
      tremor, neuropathic pain and migraine, and psychiatric disorders, including
      anxiety, schizophrenia and bipolar disorder. Many of the AEDs have various
      targets of action in the synapse and have several proposed relevant mechanisms of
      action in epilepsy and in other disorders. Pathophysiological processes disturb
      neuronal excitability by modulating ion channels, receptors and intracellular
      signalling pathways, and these are targets for the pharmacological action of
      various AEDs. Attention is focused on the glutamatergic and GABAergic synapses.
      In psychiatric conditions such as schizophrenia and bipolar disorder, AEDs such
      as valproate, carbamazepine and lamotrigine appear to have clear roles based on
      their effect on intracellular pathways. On the other hand, some AEDs, e.g.
      topiramate, have efficacy for nonpsychiatric disorders including migraine,
      possibly by enhancing GABAergic and reducing glutamatergic neurotransmission.
      AEDs that seem to enhance GABAergic neurotransmission, e.g. tiagabine, valproate,
      gabapentin and possibly levetiracetam, may have a role in treating neurological
      disorders such as essential tremor, or anxiety disorders. AEDs with effects on
      voltage-gated sodium or calcium channels may be advantageous in treating
      neuropathic pain, e.g. gabapentin, pregabalin, carbamazepine, oxcarbazepine,
      lamotrigine and valproate. Co-morbid conditions associated with epilepsy, such as
      mood disorders and migraine, may often respond to treatment with AEDs. Other
      possible disorders where AEDs may be of clinical importance include cancer, HIV
      infection, drug and alcohol abuse, and also in neuroprotection. A future
      challenge is to evaluate the second-generation AEDs in non-epilepsy disorders and
      to design clinical trials to study their effects in such disorders in paediatric
      patients. Differentiation between the main mechanisms of action of the AEDs needs
      more consideration in drug selection for tailored treatment of the various non
      epilepsy disorders.

PMID- 18072816
TI  - National use of thrombolysis with alteplase for acute ischaemic stroke via
      telemedicine in Denmark: a model of budgetary impact and cost effectiveness.
AB  - AIM: The purpose of this analysis was to assess the budgetary impact and cost
      effectiveness of the national use of thrombolysis with alteplase (recombinant
      tissue plasminogen activator; rt-PA) for acute ischaemic stroke via telemedicine
      in Denmark. METHODS: Computations were based on a Danish health economic model of
      thrombolysis treatment of acute ischaemic stroke via telemedicine. Cost data for
      stroke units and satellite clinics were taken from the first practical
      experiences in Denmark with implementing thrombolysis via telemedical linkage to
      the Stroke Department at Aarhus University Hospital. Effectiveness data were
      taken from a published pooled analysis of results from randomized controlled
      trials of alteplase. RESULTS: The calculations showed that the additional total
      costs to the hospitals of implementing thrombolysis with alteplase for acute
      ischaemic stroke via telemedicine were approximately $US3.0 (range 2.0-5.8)
      million per year in the case of five centres and five satellite clinics, or
      $US3.6 (range 2.4-7.0) million per year based on seven centres and seven
      satellite clinics. The incremental cost-effectiveness ratio was calculated to be
      approximately $US50,000 when taking a short time perspective (1 year), but
      thrombolysis was dominant (both cheaper and more effective) after as little as 2
      years and cost effectiveness improved over longer time scales. CONCLUSION: The
      budgetary impact of using thrombolysis with alteplase for acute ischaemic stroke
      via telemedicine depends on the existing capacity and organizational conditions
      at the local hospitals. The health economic model computations suggest that the
      macroeconomic costs may balance with savings in care and rehabilitation after as
      little as 2 years, and that potentially large long-term savings are associated
      with thrombolysis with alteplase delivered by telemedicine, although the long
      term calculations are uncertain.

PMID- 18072814
TI  - Quetiapine: dose-response relationship in schizophrenia.
AB  - Quetiapine is a widely used second-generation antipsychotic that is effective in
      the treatment of schizophrenia and bipolar mania. In recent years, various
      publications have suggested the possibility that, in some patients, higher than
      licensed dosages are necessary for full therapeutic effect. A 'high-dose' theory
      of quetiapine activity has developed, leading many prescribers to disregard the
      formal upper limit of the quetiapine dosage range (750 or 800 mg/day, depending
      on local labelling). In this review, we examine the clinical and neuroimaging
      data relating to the use of quetiapine in acute exacerbations of schizophrenia.
      Fixed-dose efficacy studies of immediate-release (IR) quetiapine suggest dosages
      of quetiapine of 150-450 mg/day are more effective than placebo and no less
      effective than dosages of 600 or 750 mg/day. A fixed-dose study of extended
      release quetiapine indicated that dosages of 600 and 800 mg/day were equally
      efficacious and numerically superior to 400 mg/day. Dosages of IR quetiapine
      averaging between 254 and 525 mg/day have been shown to be equivalent in efficacy
      to standard dosages of conventional and other atypical antipsychotics. Pooled
      data support these findings. Effectiveness studies using quetiapine in daily
      doses averaging between 565 and 653 mg revealed quetiapine to be somewhat less
      effective than some comparator drugs. Support for the use of high-dosage
      quetiapine (>800 mg/day) is very limited: case reports, albeit numerous, describe
      quetiapine as showing therapeutic effects only at dosages above the licensed
      range; some data suggest widespread use of higher dosages in practice; and
      neuroimaging data suggest inadequate dopamine receptor occupancy at standard
      dosages (although these findings may reflect the low affinity of quetiapine for
      dopamine receptors). Overall, robust controlled data strongly suggest that the
      standard dosage range for quetiapine is appropriate for clinical use. The balance
      of evidence does not support the belief that higher dosages are required for full
      therapeutic effect, although higher dosage trials are ultimately required to
      confirm or refute this hypothesis.

PMID- 18072817
TI  - Spotlight on rasagiline in Parkinson's disease.
AB  - Rasagiline (Azilect) is a novel, selective, irreversible second-generation
      inhibitor of monoamine oxidase type B (MAO-B). It is administered orally once
      daily and is approved in the US, Canada, Mexico, Israel and the EU for use as
      monotherapy and as adjunct therapy in the treatment of Parkinson's disease.
      Results of well designed clinical studies indicate that rasagiline is effective
      as initial monotherapy and improves Parkinson's symptomatology in patients with
      early Parkinson's disease. In addition, when administered in conjunction with
      levodopa, in patients with moderate to advanced disease and motor fluctuations,
      rasagiline reduces mean daily 'off' time and increases daily 'on' time without
      troublesome dyskinesias, compared with controls. Rasagiline is generally well
      tolerated as monotherapy and adjunctive therapy and is administered once daily.
      Thus, rasagiline, administered as a simple and convenient dosage regimen, is a
      well tolerated and effective option for monotherapy in patients with early
      Parkinson's disease and for adjunctive therapy in patients with moderate to
      advanced disease.

PMID- 18072818
TI  - Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and
      structural-functional synergies with cell membrane phospholipids.
AB  - The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid
      (EPA) are orthomolecular, conditionally essential nutrients that enhance quality
      of life and lower the risk of premature death. They function exclusively via cell
      membranes, in which they are anchored by phospholipid molecules. DHA is proven
      essential to pre- and postnatal brain development, whereas EPA seems more
      influential on behavior and mood. Both DHA and EPA generate neuroprotective
      metabolites. In double-blind, randomized, controlled trials, DHA and EPA
      combinations have been shown to benefit attention deficit/hyperactivity disorder
      (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective
      disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and
      bipolar disorder, with promising results in schizophrenia and initial benefit for
      borderline personality disorder. Accelerated cognitive decline and mild cognitive
      impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and
      supplementation has improved cognitive function. Huntington disease has responded
      to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids
      into the same molecule have shown marked promise in early clinical trials.
      Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate
      AD/HD symptoms. Krill omega-3 phospholipids, containing mostly
      phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed
      conventional fish oil DHA/EPA triglycerides in double-blind trials for
      premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles.
      Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C
      reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA
      together with phospholipids and membrane antioxidants to achieve a triple cell
      membrane synergy may further diversify their currently wide range of clinical
      applications.

PMID- 18072819
TI  - An examination of the evidence supporting the association of dietary cholesterol
      and saturated fats with serum cholesterol and development of coronary heart
      disease.
AB  - The lipid hypothesis is the basis for much of the contemporary diet advice and
      drug therapy aimed at preventing coronary heart disease (CHD), and was developed
      from a sequential association of dietary lipids, cholesterol, and CHD nearly 100
      years ago. The lipid hypothesis considers pathological changes that relate to the
      end stage of the complex chronic condition summarized as CHD, not to its genesis.
      Ongoing research provides only inconclusive evidence of the effects of
      modification of total, saturated, monounsaturated, or polyunsaturated fats on
      cardiovascular morbidity and mortality. 3-Hydroxy-3-methyl-glutaryl coenzyme A
      (HMG-CoA) reductase inhibitors or statins, the highest selling drugs in medical
      history, may provide evidence that the lipid hypothesis is based on erroneous
      assumptions, since some of the mechanisms of action of statins seem to be
      independent of cholesterol reduction. This article assesses the methodology and
      assumptions underlying the early studies that gave rise to the current assumption
      of a causal relationship between dietary fat consumption and CHD. It argues that
      flaws in methodology have led to inaccurate and highly debatable conclusions. It
      assesses research supporting criticism of these early studies and considers other
      factors that may influence CHD. It offers alternative interpretations of the use
      of statins in controlling CHD. Finally, it provides an historical context
      suggesting different causes of CHD that have no relation to fat intake.

PMID- 18072820
TI  - Emerging therapies to treat frailty syndrome in the elderly.
AB  - Frailty syndrome (FS) has become increasingly recognized as a major predictor of
      co-morbidities and mortality in older individuals. Interventions with the
      potential to benefit frail elders include nutritional supplementation (vitamins
      D, carotenoids, creatine, dehydroepiandrosterone (DHEA), and beta-hydroxy-beta
      methylbutyrate) and exercise modalities (tai chi and cobblestone walking). While
      these have not been explicitly tested for their impact on FS, vitamin D
      supplementation appears to offer significant promise in enhancing long-term
      health of the elderly. Exercise modalities such as tai chi and cobblestone
      walking, because of probable low risk and ease of participation, may also confer
      benefit. Additional studies are needed to investigate interventions that directly
      prevent, delay, and/or ameliorate frailty. Successful therapies may well involve
      multi-component approaches utilizing a combination of medication, nutritional
      supplementation, and exercise.

PMID- 18072821
TI  - D-Limonene: safety and clinical applications.
AB  - D-limonene is one of the most common terpenes in nature. It is a major
      constituent in several citrus oils (orange, lemon, mandarin, lime, and
      grapefruit). D-limonene is listed in the Code of Federal Regulations as generally
      recognized as safe (GRAS) for a flavoring agent and can be found in common food
      items such as fruit juices, soft drinks, baked goods, ice cream, and pudding. D
      limonene is considered to have fairly low toxicity. It has been tested for
      carcinogenicity in mice and rats. Although initial results showed d-limonene
      increased the incidence of renal tubular tumors in male rats, female rats and
      mice in both genders showed no evidence of any tumor. Subsequent studies have
      determined how these tumors occur and established that d-limonene does not pose a
      mutagenic, carcinogenic, or nephrotoxic risk to humans. In humans, d-limonene has
      demonstrated low toxicity after single and repeated dosing for up to one year.
      Being a solvent of cholesterol, d-limonene has been used clinically to dissolve
      cholesterol-containing gallstones. Because of its gastric acid neutralizing
      effect and its support of normal peristalsis, it has also been used for relief of
      heartburn and gastroesophageal reflux (GERD). D-limonene has well-established
      chemopreventive activity against many types of cancer. Evidence from a phase I
      clinical trial demonstrated a partial response in a patient with breast cancer
      and stable disease for more than six months in three patients with colorectal
      cancer.

PMID- 18072822
TI  - Efficacy and safety of chitosan HEP-40 in the management of hypercholesterolemia:
      a randomized, multicenter, placebo-controlled trial.
AB  - Hypercholesterolemia is an important risk factor for cardiovascular disease
      (CVD). OBJECTIVE: To compare the efficacy of a 12-week treatment regimen with HEP
      40 low-molecular weight chitosan given at daily doses of 1,200 mg, 1,600 mg, and
      2,400 mg in reducing serum low-density lipoprotein cholesterol (LDL-C) in
      patients with low-to-moderate hypercholesterolemia. DESIGN: The study was a 16
      week, multicenter, placebo-controlled, randomized study. Eligible patients were
      treatment-naive for lipid-lowering medications. Patients were randomly assigned
      to HEP-40 at the following doses: 400 mg three times daily, 800 mg twice daily,
      800 mg three times daily, 2,400 mg once daily, or placebo for 12 weeks. The main
      outcome measure was the percent change in LDL-C after four weeks of treatment.
      RESULTS: Out of 283 patients screened, 105 (37.1%) fulfilled the inclusion
      criteria and 95 (90.4%) completed the study. The mean (SD) age was 53 (11) years
      and 62.3 percent were male. The majority of patients (82.9%) were at low 10-year
      risk for CVD. The results showed an overall treatment effect (p=0.040) with the
      highest difference from the placebo group observed for the HEP-40 2,400-mg once
      daily group (-16.9%, p=0.002), followed by 400 mg three times daily (-11.1%,
      p=0.054), 800 mg three times daily (-9.7%, p=0.065), and 800 mg twice daily (
      8.7%, p=0.101). There were 29 predominantly mild adverse events reported by 24
      (23%) patients related to the study treatment, most frequently constipation
      (3.0%) and diarrhea (3.0%). CONCLUSION: HEP-40 low-molecular weight chitosan,
      although not as effective as statins, is efficacious and safe in lowering LDL-C
      concentrations in treatment-naive patients with low-to-moderate
      hypercholesterolemia.

PMID- 18072823
TI  - Gamma-aminobutyric acid (GABA), Monograph.

PMID- 18072824
TI  - Urtica dioica; Urtica urens (nettle). Monograph.

PMID- 18072825
TI  - Gambling, health and age: data from the National Epidemiologic Survey on Alcohol
      and Related Conditions.
AB  - The health effects of recreational gambling are presently unclear, particularly
      across age groups. Theories of healthy aging suggest that social activities,
      including gambling, may be beneficial to the health of older adults. Using cross
      sectional data from the National Epidemiologic Survey on Alcohol and Related
      Conditions (N=43,093), the authors examined associations between gambling
      (categorized as nongambling, recreational gambling, or problem/pathological
      gambling) and health and functioning measures stratified by age (40-64 years and
      >/=65). Problem/pathological gambling was uniformly associated with poorer health
      measures among both younger and older adults. Among younger respondents, poorer
      health measures were also found among recreational gamblers. However, among older
      respondents, recreational gambling was associated not only with some negative
      measures (e.g., obesity) but also with some positive measures (e.g., better
      physical and mental functioning). Longitudinal studies are needed to clarify the
      relationship between gambling and health in older adults in the context of
      healthy aging.

PMID- 18072826
TI  - Inference in regression models of heavily skewed alcohol use data: a comparison
      of ordinary least squares, generalized linear models, and bootstrap resampling.
AB  - Analysis of alcohol use data and other low base rate risk behaviors using
      ordinary least squares regression models can be problematic. This article
      presents 2 alternative statistical approaches, generalized linear models and
      bootstrapping, that may be more appropriate for such data. First, the basic
      theory behind the approaches is presented. Then, using a data set of alcohol use
      behaviors and consequences, results based on these approaches are contrasted with
      the results from ordinary least squares regression. The less traditional
      approaches consistently demonstrated better fit with model assumptions, as
      demonstrated by graphical analysis of residuals, and identified more significant
      variables potentially resulting in theoretically different interpretations of the
      models of alcohol use. In conclusion, these models show significant promise for
      furthering the understanding of alcohol-related behaviors.

PMID- 18072828
TI  - Social dominance mediates the association of testosterone and neurobehavioral
      disinhibition with risk for substance use disorder.
AB  - This investigation determined the influence of testosterone and neurobehavioral
      disinhibition (ND) on risk for substance use disorder (SUD). Testosterone level
      during puberty was hypothesized to promote social dominance associated with norm
      violating behavior that, in turn, predisposes individuals to use of illicit drugs
      and, subsequently, SUD. Using a prospective paradigm, the authors recruited 179
      boys (mean age=11.62 years, SD=0.88) and followed up when participants were ages
      12-14, 16, 19, and 22. Results indicated that social dominance/norm-violating
      behavior (SD/NVB) at age 16 mediated the association between testosterone level
      (ages 12-14) and SUD (age 22). In addition, SD/NVB mediated the association
      between ND and SUD. These findings suggest that development of SUD is influenced
      by androgen-dependent and neurobehavioral processes via a social motivational
      style characterized by SD/NVB.

PMID- 18072827
TI  - Examination of the mediational influences of peer norms, environmental
      influences, and parent communications on heavy drinking in athletes and
      nonathletes.
AB  - The present study used perspectives from the general literature on college
      alcohol consumption to examine mediational influences of peer, environmental, and
      parental variables on heavy drinking for student athlete and nonathlete samples.
      Eight hundred thirty-five freshmen who differed in organized sports involvement
      were compared on heavy drinking outcomes, peer norms, environmental influences,
      and parental communication. College athletes reported significantly more heavy
      drinking experiences than nonathletes. Peer norms, environmental influences, and
      parental communication were all significant mediators of the athlete-heavy
      drinking relationship. Athletes reported a higher perception of peer drinking,
      peer approval of drinking, higher alcohol availability, and direct drink offers,
      which, in turn, were related to higher rates of heavy drinking. Parental
      communication mediated the athlete-heavy drinking relationship differently,
      depending on the specific topic of conversation. Discussion surrounding the
      importance of incorporating a variety of interventions aimed at reducing
      collegiate athlete drinking on the basis of the peer, environmental, and parental
      influences observed in the present analyses are presented. Limitations and
      directions for future research are also noted.

PMID- 18072829
TI  - Measurement of smoking outcome expectancies in children: the Smoking Consequences
      Questionnaire-Child.
AB  - A measure of smoking outcome expectancies was developed for children ages 7-12
      years. Confirmatory factor analysis (CFA) was used to determine whether a 1-, 2-,
      3-, or 4-factor solution was most appropriate for the data set. CFA revealed that
      the 3-factor model produced the most adequate fit (Positive Reinforcement,
      Negative Consequences, and Weight Control). The resulting 15-item measure was
      named the Smoking Consequences Questionnaire-Child (SCQ-C). The fit of the 3
      dimensional structure was then examined separately for 3 age groups representing
      young (7- to 8-year-old), middle (9- to 10-year-old), and old (11- to 13-year
      old) children. Overall, the 3-factor structure fit the data well for the 3
      groups. As such, we examined the relations of the 3 scales with antecedent
      variables for the entire sample. The Positive Reinforcement scale was associated
      with children's smoking behavior and having a family member or peers who smoked.
      The Negative Consequences scale was inversely related to having a family member
      or peer who smoked.

PMID- 18072830
TI  - Spatial working memory performance and fMRI activation interaction in abstinent
      adolescent marijuana users.
AB  - Previous studies have suggested neural disruption and reorganization in adult
      marijuana users. However, it remains unclear whether these effects persist in
      adolescents after 28 days of abstinence and, if they do, what Performance x Brain
      Response interactions occur. Adolescent marijuana users (n=17) and controls
      (n=17) aged 16-18 years were recruited from local schools. Functional magnetic
      resonance imaging data were collected after 28 days' monitored abstinence as
      participants performed a spatial working memory task. Marijuana users show
      Performance x Brain Response interactions in the bilateral temporal lobes, left
      anterior cingulate, left parahippocampal gyrus, and right thalamus (clusters
      >/=1358 microl; p<.05), although groups do not differ on behavioral measures of
      task performance. Marijuana users show differences in brain response to a spatial
      working memory task despite adequate performance, suggesting a different approach
      to the task via altered neural pathways.

PMID- 18072831
TI  - The impact of continuing care adherence on environmental risks, substance use,
      and substance-related problems following adolescent residential treatment.
AB  - The effectiveness of adolescent treatment to reduce substance use has been
      demonstrated by a number of different literature reviews, yet longer term outcome
      studies have suggested that continued alcohol and other drug use is common.
      Participation in continuing care services and reductions in environmental risk
      factors (e.g., peer substance use or alcohol or drug use in the home) have both
      been found to be associated with improved posttreatment substance use. The
      authors conducted Path analysis to examine the experimental direct effect of the
      Assertive Continuing Care Protocol (S. H. Godley, M. D. Godley, & M. L. Dennis,
      2001) on general continuing care adherence following residential treatment and
      the protocol's indirect effect (via general continuing care adherence) on social
      and environmental risk factors, as well as subsequent substance use and substance
      related problems. Supporting previous findings, the final model indicates that
      greater adherence to continuing care is associated with reductions in
      environmental risk, which in turn is associated with reduced adolescent substance
      use and substance-related problems 9 months after discharge from residential
      treatment.

PMID- 18072832
TI  - The theory of planned behavior as a model of heavy episodic drinking among
      college students.
AB  - This study provided a simultaneous confirmatory test of the theory of planned
      behavior (TPB) in predicting heavy episodic drinking (HED) among college
      students. It was hypothesized that past HED, drinking attitudes, subjective
      norms, and drinking refusal self-efficacy would predict intention, which would,
      in turn, predict future HED. Participants consisted of 131 college drinkers (63%
      women) who reported having engaged in HED in the previous 2 weeks. Participants
      were recruited and completed questionnaires within the context of a larger
      intervention study (see Collins & Carey, 2005). Latent factor structural equation
      modeling was used to test the ability of the TPB to predict HED. Chi-square tests
      and fit indices indicated good fit for the final structural models. Self-efficacy
      and attitudes but not subjective norms significantly predicted baseline
      intention, and intention and past HED predicted future HED. Contrary to
      hypotheses, however, a structural model excluding past HED provided a better fit
      than a model including it. Although further studies must be conducted before a
      definitive conclusion is reached, a TPB model excluding past behavior, which is
      arguably more parsimonious and theory driven, may predict HED among college
      drinkers better than a model including past behavior.

PMID- 18072833
TI  - Assessment of risk for substance use disorder consequent to consumption of
      illegal drugs: psychometric validation of the neurobehavior disinhibition trait.
AB  - Previous research has shown that the trait neurobehavior disinhibition (ND),
      which consists of affect, behavior, and cognitive indicators of self-regulation,
      is a significant predictor of substance use disorder (SUD) between childhood and
      young adulthood. The authors evaluated the psychometric properties of the ND
      trait in 278 boys evaluated at ages 10-12 and 16 years. ND score significantly
      predicted SUD and outcomes that commonly manifest in tandem with SUD by age 19,
      such as violence, arrests, committing crime while intoxicated, and concussion
      injury. In addition to predictive validity, the ND trait was found to have good
      construct, discriminative, and concurrent validity, as well as good test-retest
      and internal reliability. The ND trait may be useful for detecting youths at high
      risk for developing SUD and related outcomes.

PMID- 18072834
TI  - Overcoming adolescents' resistance to anti-inhalant appeals.
AB  - This research was concerned with factors that affect adolescents' evaluations of
      persuasive anti-inhalant messages and the association of these evaluations with
      usage intentions. Sixth and 7th graders (N=894) received anti-inhalant messages
      that varied as a result of the factorial combination of message source (doctor or
      peer), suggested harm (social or physical), and target (message was addressed
      directly or indirectly to receivers). Manipulated variables were crossed with
      inhalant-user status (resolute nonuser, vulnerable nonuser, and user).
      Significant (p<.01) target and status effects on message evaluation were found.
      Significant interactions of status with each of the manipulated variables also
      emerged. Users were resistant to threatened physical harms, but suggested harms
      did not differentially affect resolute nonusers or vulnerable nonusers. Users and
      vulnerable nonusers evaluated the message more positively when targeted
      indirectly (p<.05). Vulnerable nonusers were more receptive to peer sources,
      whereas users preferred adult sources. Message evaluation was significantly
      associated with inhalant usage intentions (r=-.22), and this association held
      even after the contributions of sex, sensation seeking, acculturation, prior use,
      familism, and assumed peer usage were accounted for in a multiple regression
      analysis (overall R(2)=.24).

PMID- 18072835
TI  - Children's beliefs about substance use: an examination of age differences in
      implicit and explicit cognitive precursors of substance use initiation.
AB  - Cognitive models conceptualize attitudes and beliefs about substance use (SU) as
      proximal mediators of a variety of risk and protective factors for SU.
      Researchers have distinguished implicit and explicit cognition, but limited
      research has examined this distinction in the early stages of SU. The authors'
      goal was to examine age differences in implicit and explicit SU cognitions to
      clarify proximal cognitive processes that may be involved in early SU. Alcohol-
      and cigarette-naive children (N=76; 69.7% male; M age=11.8 years) completed the
      laboratory-based experiment. Likelihood ratings of costs and benefits of use
      assessed explicit cognitions, and a priming task assessed implicit cognitions.
      Regardless of age, children perceived costs of drinking alcohol and smoking as
      more likely than benefits. This discrepancy was smaller for older children,
      although this age difference was weaker for costs and benefits of cigarette use.
      Strong positive implicit alcohol use cognitions were apparent regardless of age.
      However, age differences were found for implicit cigarette use cognition. Older
      children were more positive about cigarette use. Findings suggest the importance
      of distinguishing explicit and implicit cognition for etiological models of early
      SU.

PMID- 18072836
TI  - Comparing gain- and loss-framed messages for smoking cessation with sustained
      release bupropion: a randomized controlled trial.
AB  - Prospect theory suggests that because smoking cessation is a prevention behavior
      with a fairly certain outcome, gain-framed messages will be more persuasive than
      loss-framed messages when attempting to encourage smoking cessation. To test this
      hypothesis, the authors randomly assigned participants (N=258) in a clinical
      trial to either a gain- or loss-framed condition, in which they received
      factually equivalent video and printed messages encouraging smoking cessation
      that emphasized either the benefits of quitting (gains) or the costs of
      continuing to smoke (losses), respectively. All participants received open label
      sustained-release bupropion (300 mg/day) for 7 weeks. In the intent-to-treat
      analysis, the difference between the experimental groups by either point
      prevalence or continuous abstinence was not statistically significant. Among 170
      treatment completers, however, a significantly higher proportion of participants
      were continuously abstinent in the gain-framed condition as compared with the
      loss-framed condition. These data suggest that gain-framed messages may be more
      persuasive than loss-framed messages in promoting early success in smoking
      cessation for participants who are engaged in treatment.

PMID- 18072837
TI  - Evaluations and expectancies of alcohol and marijuana problems among college
      students.
AB  - Two studies examined the associations between evaluations (good-bad) and expected
      likelihood (likely-unlikely) of alcohol- and marijuana-related problems and
      hazardous consumption and problems among college students. Participants provided
      data on alcohol use, alcohol-related problems, and expectancies and evaluations
      of alcohol problems; marijuana use indices, marijuana-related problems, marijuana
      effect expectancies, and likelihood and evaluations of marijuana problems.
      Evaluations of alcohol problems were positively related to the number of binge
      drinking occasions and alcohol-related problems. The interaction between
      evaluations and expectancies was significant in predicting the number of binge
      drinking occasions. Expectancies demonstrated a curvilinear relationship with
      binge drinking and alcohol-related problems. Marijuana users evaluated marijuana
      related problems as less negative and less likely to occur than did nonusers.
      Expectancies, but not evaluations, of negative consequences were significantly
      associated with marijuana use intensity. Expectancies of problems demonstrated a
      curvilinear relationship with marijuana-use intensity and marijuana problems. Men
      evaluated alcohol and marijuana problems less negatively than did women. In
      summary, the expected likelihood of alcohol-marijuana problems and the evaluation
      of such problems represent a vulnerability factor associated with increased
      liability for hazardous alcohol and marijuana use.

PMID- 18072838
TI  - Effects of alcohol sensitivity on P3 event-related potential reactivity to
      alcohol cues.
AB  - Although alcoholics and individuals at risk for alcoholism often show smaller
      amplitude of the P3 event-related brain potential (ERP), recent data (K.
      Namkoong, E. Lee, C. H. Lee, B. O. Lee, & S. K. An, 2004) indicate that alcohol
      related cues elicit larger P3 amplitude in alcoholics than in controls. Little is
      known concerning the ERP profiles or alcohol cue reactivity of social drinkers at
      risk for alcoholism due to low sensitivity to alcohol's effects. Participants
      differing in alcohol sensitivity viewed images of alcoholic and nonalcoholic
      beverages while ERPs were recorded and provided information about their alcohol
      use patterns at baseline and 4 months later. Compared to high-sensitivity
      participants, those low in sensitivity showed larger P3s to alcohol cues, even
      when recent alcohol use was statistically controlled for. Moreover, the P3
      elicited by alcohol cues predicted alcohol use at follow-up, a finding supporting
      the idea that P3 amplitude reflects the motivational significance of substance
      related cues. These findings point to risk status, not consumption history, as an
      important predictor of cue reactivity effects.

PMID- 18072839
TI  - The role of experience in liking "read-to-drink" alcoholic beverages.
AB  - Ready-to-drinks (RTDs) are composed of an alcoholic component and a soft-drink
      base and are primarily consumed by a youth market. The authors explored whether
      liking and experience with an RTD soft-drink base predicts liking for the RTD.
      Participants (N=350) from ages 12 to 30 years sampled 3 RTDs and their respective
      soft-drink and alcoholic components. For milk- and fruit-based RTDs, liking for
      and familiarity with their soft-drink base was the best predictor of liking for
      and familiarity with the RTD itself. For the Coke-based RTD, familiarity with and
      liking for bourbon best predicted familiarity with and liking for the RTD. All of
      these effects were consistent across blind and nonblind testing. The authors'
      results suggest that where there is perceptual similarity between the RTD and its
      soft-drink base, these beverages may provide an easy transition into alcohol
      consumption for novice drinkers.

PMID- 18072840
TI  - Concurrent brief versus intensive smoking intervention during alcohol dependence
      treatment.
AB  - Alcohol dependent smokers (N=118) enrolled in an intensive outpatient substance
      abuse treatment program were randomized to a concurrent brief or intensive
      smoking cessation intervention. Brief treatment consisted of a 15-min counseling
      session with 5 min of follow-up. Intensive intervention consisted of three 1-hr
      counseling sessions plus 8 weeks of nicotine patch therapy. The cigarette
      abstinence rate, verified by breath carbon monoxide, was significantly higher for
      the intensive treatment group (27.5%) versus the rate for the brief treatment
      group (6.6%) at 1 month after the quit date but not at 6 months, when abstinence
      rates fell to 9.1% for the intensive treatment group and 2.1% for the brief
      treatment group. Smoking treatment assignment did not significantly impact
      alcohol outcomes. Although intensive smoking treatment was associated with higher
      rates of short-term tobacco abstinence, other, perhaps more intensive, smoking
      interventions are needed to produce lasting smoking cessation in alcohol
      dependent smokers.

PMID- 18072841
TI  - Mediators of the association between narcissism and compulsive buying: the roles
      of materialism and impulse control.
AB  - Building upon past research about the guiding values and self-regulation
      difficulties of people with narcissistic personalities, this study tested a model
      of the association between narcissism and compulsive consumption. In data
      obtained from a sample of undergraduate consumers (N=238) with varying degrees of
      spending problems, positive associations emerged between narcissism, materialism,
      and compulsive buying. Impulse control was negatively correlated with each of
      these variables. Mediation tests revealed that both impulse control and
      materialism accounted for significant portions of the shared variance between
      narcissism and compulsive consumption. These findings highlight the importance of
      both personal values and impulse control as correlates of addictive buying. They
      also add to growing evidence that people who are relatively narcissistic are poor
      self-regulators who may be at risk of developing a variety of addictive
      behaviors.

PMID- 18072842
TI  - Brief motivational intervention with homeless adolescents: evaluating effects on
      substance use and service utilization.
AB  - A brief motivational intervention with 117 homeless adolescents was evaluated
      using a randomized design and 3-month follow-up. The intervention was designed to
      raise youths' concerns about their substance use, support harm reduction, and
      encourage greater service utilization at a collaborating agency. The study was
      designed to strengthen initial promising results of an earlier study (P. L.
      Peterson, J. S. Baer, E. A. Wells, J. A. Ginzler, & S. B. Garrett, 2006). Several
      modifications in the clinical protocol were included to enhance engagement with
      the intervention. Analyses revealed no significant benefits for intervention
      participants when homeless youths' substance use rates were compared with those
      of control participants. Service utilization during the intervention period
      increased for those receiving the intervention but returned to baseline levels at
      follow-up. Participants reported overall reductions in substance use over time.
      Differences between sampling methods for the current and previous study are
      discussed, as are the limitations of brief interventions with this population.
      Future research needs to elucidate mechanisms of change and service engagement
      for highly vulnerable youth.

PMID- 18072843
TI  - Apples and oranges? Comparing indirect measures of alcohol-related cognition
      predicting alcohol use in at-risk adolescents.
AB  - Recently, there has been increased interest in the role of implicit cognitive
      processes in the development of addictive behaviors. In this study, the authors
      compared 3 indirect measures of alcohol-related cognitions in the prospective
      prediction of alcohol use in at-risk adolescents. Implicit alcohol-related
      cognitions were assessed in 88 Dutch at-risk adolescents ranging in age from 14
      to 20 years (51 males, 37 females) by means of varieties of word association
      tasks, Implicit Association Tests, and Extrinsic Affective Simon Tasks adapted
      for alcohol use. Alcohol use and alcohol-related problems were measured with self
      report questionnaires at baseline and after 1 month. Results showed that the
      indirect measures predicted unique variance in prospective alcohol use after
      controlling for the direct measure of alcohol-related cognitions and background
      variables. The results indicate that the word association tasks were the best
      indirect measure of alcohol-related cognitions. These indirect measures appear to
      assess cognitive motivational processes that affect behavior in ways not
      reflected by direct measures of alcohol-related cognitions.

PMID- 18072844
TI  - Pilot test of Project CHOICE: a voluntary afterschool intervention for middle
      school youth.
AB  - The current study reports findings from a pilot evaluation of a voluntary alcohol
      and marijuana intervention for young teens. Students at 2 middle schools
      completed 4 surveys over 2 years. During Year 2, an intervention, Project CHOICE
      (PC), was implemented at 1 school and was voluntarily attended by 13% of
      adolescents. Participants ranged from 10 to 15 years of age and were
      approximately 45% male, 45% White, 30% Latino, and 15% of mixed ethnic origin.
      Outcomes included assessments of self use and perceptions of friends' and
      schoolmates' past-month use of alcohol and marijuana. Analyses that compared PC
      participants (n=64) with a matched control sample of students (n=264) revealed
      that PC participants reported lower rates of alcohol use and lower perceptions of
      friends' marijuana use and of schoolmates' use of these substances. Random
      effects growth models indicated that self use and perceptions of friends' use of
      alcohol and marijuana increased more sharply among control school students
      (n=178) relative to students from the PC school (n=270), regardless of
      participation. Results suggest that a brief voluntary intervention attended by a
      small proportion of students can impact both individual and schoolwide substance
      related outcomes.

PMID- 18072845
TI  - Relative versus absolute measures of explicit attitudes: Implications for
      predicting diverse attitude-relevant criteria.
AB  - The authors report 4 studies exploring a self-report strategy for measuring
      explicit attitudes that uses "relative" ratings, in which respondents indicate
      how favorable or unfavorable they are compared with other people. Results
      consistently showed that attitudes measured with relative scales predicted
      relevant criterion variables (self-report of behavior, measures of knowledge,
      peer ratings of attitudes, peer ratings of behavior) better than did attitudes
      measured with more traditional "absolute" scales. The obtained pattern of
      differences in prediction by relative versus absolute measures of attitudes did
      not appear to be attributable to differential variability, social desirability
      effects, the clarity of scale-point meanings, the number of scale points, or
      overlap with subjective norms. The final study indicated that relative measures
      induce respondents to consider social comparison information and behavioral
      information when making their responses more than do absolute measures, which may
      explain the higher correlations between relative measures of attitudes and
      relevant criteria.

PMID- 18072846
TI  - The effects of nonconsciously priming emotion concepts on behavior.
AB  - Current empirical evidence regarding nonconsciously priming emotion concepts is
      limited to positively versus negatively valenced affect. This article
      demonstrates that specific, equally valenced emotion concepts can be
      nonconsciously activated, remain inaccessible to conscious awareness, and still
      affect behavior in an emotion-specific fashion. In Experiment 1A, participants
      subliminally primed with guilty emotion adjectives showed lower indulgence than
      did participants subliminally primed with sad emotion adjectives; even after the
      addition of a 5-min time delay, these results were replicated in Experiment 1B.
      Participants in the different priming conditions showed no differences in their
      subjective emotion ratings and were unaware of the emotion prime or concept
      activation. Experiments 2A and 2B replicated these findings using a helping
      measure, demonstrating that individuals primed with guilt adjectives show more
      helping than do individuals primed with sadness adjectives. In all studies,
      effects were moderated by individuals' specific emotion-response habits and
      characteristics.

PMID- 18072847
TI  - Priming us and them: automatic assimilation and contrast in group attitudes.
AB  - Social judgment theory holds that a person's own attitudes function as reference
      points, influencing the perception of others' attitudes. The authors argue that
      attitudes themselves are influenced by reference points, namely, the presumed
      attitudes of others. Whereas exposure to a group that acts as a contextual
      reference should cause attitude assimilation, exposure to a group that acts as a
      comparative reference should cause attitude contrast. In Study 1, participants
      subliminally primed with their political ingroup or outgroup endorsed more
      extreme political positions than did controls. Study 2 demonstrated that prime
      types known to uniquely facilitate assimilation and contrast enhanced the
      polarization effect in the ingroup and outgroup conditions, respectively. Study 3
      established an important boundary condition for whether group salience produces
      attitude assimilation or contrast by showing that perceived closeness to the
      elderly moderates the direction and strength of the group priming effect. The
      results suggest that the transition from assimilation to contrast occurs when a
      group ceases to function as a context and becomes a comparison point.
      Implications for social judgment theory, assimilation and contrast research, and
      conflict escalation are discussed.

PMID- 18072848
TI  - (Why) do I think what you think? Epistemic social tuning and implicit prejudice.
AB  - This research examines whether people who experience epistemic motivation (i.e.,
      a desire to acquire knowledge) came to have implicit attitudes consistent with
      the apparent beliefs of another person. People had lower implicit prejudice when
      they experienced epistemic motivation and interacted with a person who ostensibly
      held egalitarian beliefs (Experiments 1 and 2). Implicit prejudice was not
      affected when people did not experience epistemic motivation. Further evidence
      shows that this tuning of implicit attitudes occurs when beliefs are endorsed by
      another person, but not when they are brought to mind via means that do not imply
      that person's endorsement (Experiment 3). Results suggest that implicit attitudes
      of epistemically motivated people tune to the apparent beliefs of others to
      achieve shared reality.

PMID- 18072849
TI  - Motivation gains of inferior group members: a meta-analytical review.
AB  - In recent years, a growing number of studies have demonstrated that individuals
      can exert higher motivation when working in a group compared to working
      individually. This is particularly true for less capable, inferior group members.
      To aggregate these findings and to examine preconditions as well as moderating
      influences on motivation gains of inferior group members, the authors conducted a
      meta-analysis (17 studies, N=2,240). Results indicated that the overall
      motivation gain effect of inferior group members observed is moderate and
      significant (g=.60). Moderator analyses revealed substantial influences of task
      structure, performance information, physical presence, gender, and task type.

PMID- 18072850
TI  - Conflicting social motives in negotiating groups.
AB  - Negotiators' social motives (cooperative vs. individualistic) influence their
      strategic behaviors. In this study, the authors used multilevel modeling and
      analyses of strategy sequences to test hypotheses regarding how negotiators'
      social motives and the composition of the group influence group members'
      negotiation strategies. Four-person groups negotiating a 5-issue mixed-motive
      decision-making task were videotaped, and the tapes were transcribed and coded.
      Group composition included 2 homogeneous conditions (all cooperators and all
      individualists) and 3 heterogeneous conditions (3 cooperators and 1
      individualist, 2 cooperators and 2 individualists, 1 cooperator and 3
      individualists). Results showed that cooperative negotiators adjusted their use
      of integrative and distributive strategies in response to the social-motive
      composition of the group, but individualistic negotiators did not. Results from
      analyses of strategy sequences showed that cooperators responded more
      systematically to others' behaviors than did individualists. They also redirected
      the negotiation depending on group composition.

PMID- 18072851
TI  - Identity-based motivation and health.
AB  - People do not always take action to promote health, engaging instead in unhealthy
      habits and reporting fatalism about health. One important mechanism underlying
      these patterns involves identity-based motivation (D. Oyserman, 2007), the
      process by which content of social identities influences beliefs about in-group
      goals and strategies. Seven studies show the effect of identity-based motivation
      on health. Racial-ethnic minority participants view health promotion behaviors as
      White middle class and unhealthy behaviors as in-group defining (Studies 1 and
      2). Priming race-ethnicity (and low socioeconomic status) increases health
      fatalism and reduces access to health knowledge (Studies 3 and 4). Perceived
      efficacy of health-promoting activities is undermined when racial-ethnic minority
      participants who identify unhealthy behavior as in-group defining are asked to
      consider their similarities to (middle-class) Whites (Studies 5-7).

PMID- 18072852
TI  - Stereotypes help people connect with others in the community: a situated
      functional analysis of the stereotype consistency bias in communication.
AB  - Communicators tend to share more stereotype-consistent than stereotype
      inconsistent information. The authors propose and test a situated functional
      model of this stereotype consistency bias: stereotype-consistent and inconsistent
      information differentially serve 2 central functions of communication--sharing
      information and regulating relationships; depending on the communication context,
      information seen to serve these different functions better is more likely
      communicated. Results showed that stereotype-consistent information is perceived
      as more socially connective but less informative than inconsistent information,
      and when the stereotype is perceived to be highly shared in the community, more
      stereotype-consistent than inconsistent information is communicated due to its
      greater social connectivity function. These results highlight the need to examine
      communication as a dynamic and situated social activity.

PMID- 18072853
TI  - The effects of message recipients' power before and after persuasion: a self
      validation analysis.
AB  - In the present research, the authors examined the effect of a message recipient's
      power on attitude change and introduced a new mechanism by which power can affect
      social judgment. In line with prior research that suggested a link between power
      and approach tendencies, the authors hypothesized that having power increases
      confidence relative to being powerless. After demonstrating this link in
      Experiment 1, in 4 additional studies, they examined the role of power in
      persuasion as a function of when power is infused into the persuasion process. On
      the basis of the idea that power validates whatever mental content is accessible,
      they hypothesized that power would have different effects on persuasion depending
      on when power was induced. Specifically, the authors predicted that making people
      feel powerful prior to a message would validate their existing views and thus
      reduce the perceived need to attend to subsequent information. However, it was
      hypothesized that inducing power after a message has been processed would
      validate one's recently generated thoughts and thus influence the extent to which
      people rely upon their thoughts in determining their attitudes.

PMID- 18072854
TI  - Early positive emotionality as a heterogeneous trait: implications for children's
      self-regulation.
AB  - Young children's positive affect in scripted laboratory procedures and in free
      flowing social interactions may reflect the activation of related but distinct
      aspects of positive emotionality (PE), with different implications for self
      regulation. The authors observed children's PE in scripted laboratory procedures
      and in naturalistic interactions with mothers in 2 studies: at 9, 14, 22, 33, and
      45 months (the Parent-Child Study, N=112) and at 7, 15, 25, 38, and 52 months
      (the Family Study, N=102). Measures of self-regulation included effortful control
      (observed in the Parent-Child Study at 22, 33, and 45 months and in the Family
      Study at 25, 38, and 52 months) and rule-compatible conduct (observed in the
      Parent-Child Study at 56 and 73 months and in the Family Study at 38 and 52
      months). In both studies, 2 PE measures had distinct implications: PE in scripted
      procedures related negatively, whereas PE in mother-child interactions related
      positively to self-regulation. In both studies, those differential effects were
      particularly clear for children's effortful control. A view of early PE as having
      a heterogeneous nature may inform researchers' understanding of its role in the
      developing personality.

PMID- 18072855
TI  - Intuition and the correspondence between implicit and explicit self-esteem.
AB  - Four studies tested whether the perceived validity of intuition increases the
      correspondence between implicit and explicit self-esteem. Studies 1 and 2 found,
      with 2 different measures of implicit self-esteem, that people who chronically
      view their intuition as valid have more consistent implicit and explicit self
      esteem. In contrast, people with relatively low faith in their intuition had a
      negative relation between implicit and explicit self-esteem, suggesting that they
      may overcorrect their explicit self-views for the potential bias posed by
      implicit self-esteem. In Studies 3 and 4, participants who were induced to view
      their intuition as valid reported explicit self-views (self-evaluations made
      under time pressure, or state self-esteem) that were more consistent with their
      implicit self-esteem. These results suggest that people experience implicit self
      esteem as intuitive evaluations. The correspondence between implicit and explicit
      self-esteem among individuals who view their intuition as valid may suggest that
      these individuals incorporate implicit self-esteem into their explicit self
      views.

PMID- 18072856
TI  - Relations between personality and coping: a meta-analysis.
AB  - Personality may directly facilitate or constrain coping, but relations of
      personality to coping have been inconsistent across studies, suggesting a need
      for greater attention to methods and samples. This meta-analysis tested
      moderators of relations between Big Five personality traits and coping using
      2,653 effect sizes drawn from 165 samples and 33,094 participants. Personality
      was weakly related to broad coping (e.g., Engagement or Disengagement), but all 5
      traits predicted specific strategies. Extraversion and Conscientiousness
      predicted more problem-solving and cognitive restructuring, Neuroticism less.
      Neuroticism predicted problematic strategies like wishful thinking, withdrawal,
      and emotion-focused coping but, like Extraversion, also predicted support
      seeking. Personality more strongly predicted coping in young samples, stressed
      samples, and samples reporting dispositional rather than situation-specific
      coping. Daily versus retrospective coping reports and self-selected versus
      researcher-selected stressors also moderated relations between personality and
      coping. Cross-cultural differences were present, and ethnically diverse samples
      showed more protective effects of personality. Richer understanding of the role
      of personality in the coping process requires assessment of personality facets
      and specific coping strategies, use of laboratory and daily report studies, and
      multivariate analyses.

PMID- 18072857
TI  - Gender and sexual orientation differences in sexual response to sexual activities
      versus gender of actors in sexual films.
AB  - In this study, the authors investigated the hypothesis that women's sexual
      orientation and sexual responses in the laboratory correlate less highly than do
      men's because women respond primarily to the sexual activities performed by
      actors, whereas men respond primarily to the gender of the actors. The
      participants were 20 homosexual women, 27 heterosexual women, 17 homosexual men,
      and 27 heterosexual men. The videotaped stimuli included men and women engaging
      in same-sex intercourse, solitary masturbation, or nude exercise (no sexual
      activity); human male-female copulation; and animal (bonobo chimpanzee or Pan
      paniscus) copulation. Genital and subjective sexual arousal were continuously
      recorded. The genital responses of both sexes were weakest to nude exercise and
      strongest to intercourse. As predicted, however, actor gender was more important
      for men than for women, and the level of sexual activity was more important for
      women than for men. Consistent with this result, women responded genitally to
      bonobo copulation, whereas men did not. An unexpected result was that homosexual
      women responded more to nude female targets exercising and masturbating than to
      nude male targets, whereas heterosexual women responded about the same to both
      sexes at each activity level.

PMID- 18072858
TI  - Recombinant adeno-associated virus-mediated global anterograde delivery of glial
      cell line-derived neurotrophic factor to the spinal cord: comparison of
      rubrospinal and corticospinal tracts in the rat.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of
      spinal lower motoneurons. Gene delivery is a promising strategy to deliver
      therapeutic molecules to these vulnerable cells. However, definition of an
      optimal route of delivery capable of accessing neurons over a considerable extent
      of the neuraxis represents a significant logistical problem. Intramuscular vector
      injections are not ideal as this approach would involve hundreds of injections to
      completely treat an ALS patient and also would be dependent on retrograde
      transport of the viral platform of choice. Alternatively, upper motoneurons could
      deliver trophic factors over considerable distances by anterograde transport
      after a relatively localized intracerebral injection. To test this approach, the
      present study was designed to compare the corticospinal (CST) and rubrospinal
      (RST) tracts for their ability to transport recombinant adeno-associated virus
      serotype 5 (rAAV5)-derived green fluorescent protein (GFP) or glial cell line
      derived neurotrophic factor (GDNF) to the spinal cord. Unilateral injections of
      rAAV5-GFP into the red nucleus (RN) or motor cortex of normal rats produced GFP
      positive fibers in the appropriate descending tracts extending to the lumbar
      spinal cord. For both tracts, GFP-positive axonal projections into the spinal
      gray matter were consistently observed. GDNF immunohistochemistry demonstrated
      that confirmed RN injections resulted in GDNF-positive fibers projecting into
      spinal gray matter as seen in the GFP group. In contrast, confirmed cortical
      rAAV5-GDNF injections resulted in less evident staining in spinal cord. Spinal
      cord GDNF levels were elevated at distances up to 72 mm from the injection sites,
      and confirmed that RST-related GDNF transport to spinal cord surpassed CST
      associated delivery.

PMID- 18072859
TI  - Characterization of conserved viral leader RNA sequences that stimulate innate
      immunity through TLRs.
AB  - Viruses of the order Mononegavirales encompass life-threatening pathogens with
      single-stranded segmented or nonsegmented negative-strand RNA genomes. The RNA
      genomes are characterized by highly conserved sequences at the extreme
      untranslated 3' and 5' termini that are most important for virus infection and
      viral RNA synthetic processes. The 3' terminal genome regions of negative-strand
      viruses such as vesicular stomatitis virus, Sendai virus, or influenza virus
      contain a high number of conserved U and G nucleotides, and synthetic
      oligoribonucleotides encoding such sequences stimulate sequence-dependent
      cytokine responses via TLR7 and TLR8. Immune cells responding to such sequences
      include NK cells, NK/T cells, plasmacytoid, and myeloid dendritic cells, as well
      as monocytes and B cells. Strong Th1 and pro-inflammatory cytokine responses are
      also induced upon in vivo application of oligoribonucleotides. It appears
      possible that the presence of highly conserved untranslated terminal regions in
      the viral genome fulfilling fundamental functions for the viral replication may
      enable the host to induce directed innate immune defense mechanisms, by allowing
      pathogen detection through essential RNA regions that the virus cannot readily
      mutate.

PMID- 18072860
TI  - Quantification and characterization of autotransduction in retroviral vector
      producer cells.
AB  - Gene therapy has evolved into a tempting strategy for the management of cancer
      and other life-threatening diseases. Various approaches employ retroviral vectors
      to deliver the therapeutic gene. The profound knowledge about retrovirus biology
      allows the generation of increasingly advanced vector systems as well as an
      accurate assessment and management of potential safety risks. This study focuses
      on the genetic stability of retrovirus producer cells as a basic safety
      requirement and its compromise by autotransduction. It has been shown previously
      that protection of retroviral packaging systems by superinfection interference is
      not guaranteed. The current study provides insight into the extent of
      autotransduction and the time point at which it occurs, and examines strategies
      to antagonize it. Therefore, a reconstituting vector system was used that
      obviates transgene expression in virus producer cells by physically separating
      transgene and promoter. Just on infection two functional expression cassettes are
      reconstituted, causing highly efficient transgene expression in transduced cells.
      Equipped with an enhanced green fluorescent protein-encoding gene, this vector
      allowed accurate quantification of autotransduced cells, which were then isolated
      by fluorescence-activated cell sorting and further characterized. Sequencing of
      recloned integrated vector copies demonstrated that high transgene expression
      levels were strictly associated with the presence of reverse-transcribed vector
      copies. Envelope protein expression levels, however, were found to be equal in
      autotransduced and noninfected virus producer cells. Finally, the occurrence of
      autotransduction could be assigned to an early time point after transfection and
      was successfully blocked by azidothymidine treatment, yielding a stable and
      homogeneous population of noninfected retrovirus producer cells.

PMID- 18072861
TI  - Using a general model of personality to understand sex differences in the
      personality disorders.
AB  - In the present study, a general model of personality was used to evaluate sex
      bias in the personality disorders (PD). This present study compared observed sex
      differences among the personality disorders (PD) with differences expected based
      on the Five Factor Model of personality functioning (FFM). Observed sex
      differences were obtained by metaanalyzing over 30 reports. Expected sex
      differences were computed using what is known about sex differences in the FFM
      traits and how these traits relate to the PDs. Agreement between observed and
      expected sex differences was quite good for eight of ten PDs. For histrionic PD,
      the obtained sex difference was larger than expected; for schizotypal personality
      disorder, an expected sex difference was not obtained. Implications of
      understanding sex differences in terms of the FFM are discussed and suggestions
      for future research are provided.

PMID- 18072862
TI  - The role of affective instability and impulsivity in predicting future BPD
      features.
AB  - Models of borderline personality disorder (BPD) suggest that extreme levels of
      affective instability/emotional dysregulation, impulsivity, or the combination of
      these two traits account for the symptoms characteristic of BPD. The present
      study utilized longitudinal data to evaluate the ability of Personality
      Assessment Inventory-Borderline Features (PAI-BOR; Morey, 1991) subscale scores
      to predict BPD features two years later as a test of these models of BPD.
      Participants were 156 male and 194 female young adults who completed the PAI-BOR
      at age 18 and again two years later. Three models were compared: (a) Wave 1
      affective instability scores predicting Wave 2 BPD features (AI model); (b) Wave
      1 self-harm/impulsivity scores predicting Wave 2 BPD features (IMP model); and
      (c) both Wave 1 affective instability and self-harm/impulsivity scores predicting
      Wave 2 BPD features (AI-IMP model), all controlling for stabilities and within
      time covariances. Results indicated that the AI model provided the best fit to
      the data, and improved model fit over a baseline stabilities model and the other
      models tested. These results are consistent with Linehan's theory (1993) that
      emotional dysregulation drives the other BPD symptoms.

PMID- 18072863
TI  - Heterogeneity of borderline personality disorder: do the number of criteria met
      make a difference?
AB  - Many studies have compared the demographic and clinical characteristics of
      patients with and without borderline personality disorder (BPD), but there is
      limited knowledge on differences within the population of borderline patients.
      One potential index of heterogeneity is disorder severity. In the present report
      from the Rhode Island Methods to Improve Diagnostic Assessment and Services
      (MIDAS) project, we examined whether the severity of borderline personality
      disorder, as measured by the number of criteria present, is associated with co
      morbidity of Axis I and Axis II diagnoses, as well as demographic factors and
      psychosocial functioning. Two thousand three hundred psychiatric outpatients were
      interviewed with the Structured Interview for DSM-IV Personality (SIDP-IV).
      Approximately ten percent (n = 237) of the patients were diagnosed with BPD, and
      they were divided into four groups based on the number of DSM-IV criteria met, 5
      (n = 89), 6 (n = 70), 7 (n = 46), and 8 or 9 (n = 32). There were greater rates
      of drug use disorders and comorbid Axis II disorders, as well as a greater number
      of suicidal gestures, in patients meeting seven or more BPD criteria. There were
      no significant differences between the groups in the number and specific rates of
      other co-morbid Axis I disorders, other measures of psychosocial functioning, or
      demographic correlates. Sub-typing of borderline patients by the number of
      criteria met provides a limited explanation for heterogeneity within BPD
      patients.

PMID- 18072864
TI  - Evaluation of the SCID-II personality disorder traits for DSM-IV: coherence,
      discrimination, relations with general personality traits, and functional
      impairment.
AB  - The utility of the DSM personality disorder (PD) system remains a concern. The
      strategy employed represents one approach designed to evaluate and improve the
      diagnostic efficiency of the SCID-II PDs. Using a sample of 203 patients, SCID-II
      PD items-based on the criterion sets of the 10 DSM-IV PDs-were evaluated with
      respect to (a) convergent validity; (b) divergent validity; (c) relation to
      general personality traits; and (d) association with functional impairment. Only
      Borderline PD items were satisfactory on all four evaluation criteria. Histrionic
      and Obsessive-Compulsive PD items met criteria for convergent and divergent
      validity and relation to personality dimensions of the Five-Factor Model of
      Personality (FFM) but were not related to functional impairment, suggesting they
      might be reconsidered as disorders. Schizotypal PD items met three of the four
      criteria but showed no relation to FFM dimensions, suggesting that it may be a
      candidate for reassignment to Axis I.

PMID- 18072865
TI  - Using the FFM to conceptualize psychopathy: a test using a drug abusing sample.
AB  - The present study examined whether psychopathy can be understood as a
      constellation of traits from the Five Factor Model (FFM) of personality. Using a
      prototype matching approach, we examined the ability of the Revised NEO
      Personality Inventory (NEO PI-R; Costa & McCrae, 1992) to represent psychopathy
      in a sample of 297 male and female known crack cocaine abusers. Importantly, we
      examined the convergence and divergence between FFM psychopathy and other
      personality disorders assessed using the FFM. FFM psychopathy was correlated with
      self-reports of antisocial behavior, drug use, risky sex, and externalizing and
      internalizing disorder symptoms. As expected, there was overlap in the relations
      between psychopathy and several Cluster B personality disorders, but there were
      also important points of divergence. These results further extend the nomological
      network of FFM psychopathy and provide additional support for considering
      psychopathy a constellation of personality traits from a general model.

PMID- 18072866
TI  - Dimensions of DSM-IV personality disorders and life-success.
AB  - This study examined associations between dimensional representations of DSM-IV
      personality disorders and life-success in a community sample of 304 men at age
      48. Measures included a standardized social interview and the SCID-II for
      assessment of personality disorders. The identified indicators of life-success
      were factor-analyzed resulting in two moderately correlated components
      representing "status and wealth" and "successful intimate relationships."
      Avoidant, obsessivecompulsive, and narcissistic dimensional scores were
      positively associated with "status and wealth." Inverse relationships were found
      between dependent, schizotypal, schizoid, and adult antisocial personality
      disorder dimensions and this domain of life-success. Avoidant, schizoid, and
      borderline personality disorder dimensions were negatively associated with
      "successful intimate relationships." The findings suggest that although most
      personality disorders are associated with impaired psychosocial functioning and
      life-failure, some personality disorder traits (even if considered as
      pathological) can contribute positively to one important aspect of life-success:
      status and wealth.

PMID- 18072867
TI  - A five-year follow-up of patients with borderline pathology of childhood.
AB  - Borderline pathology of childhood (BPC) may be a precursor of personality
      disorders. There is a lack of data concerning outcome in adolescence. A group of
      59 adolescents, who had been treated as children in a Child Psychiatry Day
      Hospital five to seven years earlier, was evaluated. Using the child version of
      the Retrospective Diagnostic Interview for Borderlines, 28 participants had been
      diagnosed with BPC while the remaining 31 participants who did not have a history
      of BPC served as the comparison group. The youth and their parents were given a
      battery of measures assessing current psychopathology and functional status. The
      group with a history of BPC was more likely than the comparison group to exhibit
      a combination of internalizing and externalizing behavior problems. Adolescents
      with a history of BPC were more impaired than the comparison group on a global
      measure of functional status. Compared to children with no history of BPC,
      children diagnosed with BPC are more likely to display poorer functioning as
      adolescents and continue to be at risk for psychopathology during adolescence.
      Future directions for research are discussed.

PMID- 18072868
TI  - Dimensional assessment of personality pathology in female and male juvenile
      delinquents.
AB  - A developmental perspective implies similar personality pathology dimensions for
      adolescents and adults. The present study examined the applicability of a
      dimensional approach in incarcerated delinquent female and male juveniles using
      the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP
      BQ). A sample of detained adolescents (n = 146) was compared to adolescent
      students (n = 98) and a healthy control group of adults (n = 82). Additionally,
      psychopathology was assessed in the incarcerated juveniles using the Youth Self
      Report (YSR). Analyses of variance revealed higher scores on personality disorder
      traits for juveniles compared to adult controls; the highest scores were observed
      in criminal juveniles. Hypothesized relationships could be confirmed within the
      criminal sample between the DAPP factor Emotional Dysregulation and the YSR
      Internalization syndrome scale, and between the DAPP factor Dissocial Behavior
      and the YSR Externalization syndrome scale. Moreover, gender differences in the
      criminal sample are discussed. Results indicate that the DAPP-BQ can assess
      personality disorder traits in delinquent and nondetained juveniles with
      sufficient group and criterion validity.

PMID- 18072869
TI  - Social consequences of personality disorders: probability and timing of marriage
      and probability of marital disruption.
AB  - The associations between DSM-IV personality disorders and probability of
      marriage, early marriage, and marital disruption were evaluated among people that
      participated in the National Epidemiologic Survey on Alcohol and Related
      Conditions, which is a nationally representative face-to-face survey of 43,093
      respondents, 18 years and older. Participants completed a structured interview
      for the diagnosis of seven personality disorders, and provided information about
      the occurrence and timing of marriage and marital disruption. Results suggest
      that personality disorders were associated with decreased probability of
      marriage, increased probability of early marriage, and increased probability of
      marital disruption. These findings suggest that personality disorders have
      substantial consequences for the probability and timing of marriage and
      probability of marital disruption.

PMID- 18072871
TI  - Effects of epidural administration of dexmedetomidine on the minimum alveolar
      concentration of isoflurane in dogs.
AB  - Objective-To evaluate the effects of epidural administration of 3 doses of
      dexmedetomidine on isoflurane minimum alveolar concentration (MAC) and
      characterize changes in bispectral index (BIS) induced by nociceptive stimulation
      used for MAC determination in dogs. Animals-6 adult dogs. Procedures-Isoflurane
      anesthetized dogs received physiologic saline (0.9% NaCl) solution (control
      treatment) or dexmedetomidine (1.5 [DEX1.5], 3.0 [DEX3], or 6.0 [DEX6] mug/kg)
      epidurally in a crossover study. Isoflurane MAC (determined by use of electrical
      nociceptive stimulation of the hind limb) was targeted to be accomplished at 2
      and 4.5 hours. Changes in BIS attributable to nociceptive stimulation and
      cardiopulmonary data were recorded at each MAC determination. Results-With the
      control treatment, mean +/- SD MAC values did not change over time (1.57 +/-
      0.23% and 1.55 +/- 0.25% at 2 and 4.5 hours, respectively). Compared with the
      control treatment, MAC was significantly lower at 2 hours (13% reduction) but not
      at 4.5 hours (7% reduction) in DEX1.5-treated dogs and significantly lower at 2
      hours (29% reduction) and 4.5 hours (13% reduction) in DEX3-treated dogs. The
      DEX6 treatment yielded the greatest MAC reduction (31% and 22% at 2 and 4.5
      hours, respectively). During all treatments, noxious stimulation increased BIS;
      but changes in BIS were correlated with increases in electromyographic activity.
      Conclusions and Clinical Relevance-In dogs, epidural administration of
      dexmedetomidine resulted in dose-dependent decreases in isoflurane MAC and that
      effect decreased over time. Changes in BIS during MAC determinations may not
      represent increased awareness because of the possible interference of
      electromyographic activity.

PMID- 18072872
TI  - Site specificity of fracture prediction in children.

PMID- 18072873
TI  - Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr
      results of a randomized, double-blind, placebo-, and active-controlled study.
AB  - Osteoporosis is an increasingly common health concern in postmenopausal women. In
      a 2-yr phase III study, bazedoxifene prevented bone loss, reduced bone turnover,
      and was well tolerated in early postmenopausal women with normal or low BMD.
      INTRODUCTION: Bazedoxifene is a novel selective estrogen receptor modulator that
      has increased BMD and bone strength in experimental models, without stimulating
      breast or uterus. This 24-mo, randomized, double-blind study assessed the
      efficacy and safety of three doses of bazedoxifene compared with placebo and
      raloxifene in the prevention of postmenopausal osteoporosis. MATERIALS AND
      METHODS: Healthy postmenopausal women with a BMD T-score at the lumbar spine or
      femoral neck between -1.0 and -2.5 or clinical risk factors for osteoporosis were
      randomly assigned to one of five groups: bazedoxifene 10, 20, or 40 mg/d,
      placebo, or raloxifene 60 mg/d. All women received elemental calcium. Efficacy
      outcomes included changes from baseline through 24 mo in BMD of the lumbar spine,
      hip, femoral neck, and femoral trochanter and biomarkers of bone metabolism.
      RESULTS: The intent-to-treat population included 1434 women (mean age, 58 yr;
      mean time from last menstrual period, 11 yr). All doses of bazedoxifene and
      raloxifene prevented bone loss, whereas in the placebo group, there was
      significant loss of BMD at all skeletal sites. Mean differences in percent change
      in lumbar spine BMD from baseline to 24 mo relative to placebo were 1.08 +/-
      0.28%, 1.41 +/- 0.28%, 1.49 +/- 0.28%, and 1.49 +/- 0.28% for 10, 20, and 40 mg
      bazedoxifene and 60 mg raloxifene, respectively (p < 0.001 for all comparisons).
      Comparable BMD responses were observed at other body sites. Significant and
      comparable decreases in serum osteocalcin and C-telopeptide levels from baseline
      and relative to placebo with active treatment were observed as early as 3 mo and
      were sustained through study conclusion (p < 0.001). Overall incidences of
      adverse events, serious adverse events, and discontinuations caused by adverse
      events were similar between groups. The most common adverse events included
      headache, infection, arthralgia, pain, hot flush, and back pain. CONCLUSIONS:
      Treatment with bazedoxifene prevented bone loss and reduced bone turnover equally
      as well as raloxifene and was generally well tolerated in postmenopausal women
      with normal/low BMD.

PMID- 18072874
TI  - Impact exercise increases BMC during growth: an 8-year longitudinal study.
AB  - Our aim was to assess BMC of the hip over 8 yr in prepubertal children who
      participated in a 7-mo jumping intervention compared with controls who
      participated in a stretching program of equal duration. We hypothesized that
      jumpers would gain more BMC than control subjects. The data reported come from
      two cohorts of children who participated in separate, but identical, randomized,
      controlled, school-based impact exercise interventions and reflect those subjects
      who agreed to long-term follow-up (N = 57; jumpers = 33, controls = 24; 47% of
      the original participants). BMC was assessed by DXA at baseline, 7 and 19 mo
      after intervention, and annually thereafter for 5 yr (eight visits over 8 yr).
      Multilevel random effects models were constructed and used to predict change in
      BMC from baseline at each measurement occasion. After 7 mo, those children that
      completed high-impact jumping exercises had 3.6% more BMC at the hip than control
      subjects whom completed nonimpact stretching activities (p < 0.05) and 1.4% more
      BMC at the hip after nearly 8 yr (BMC adjusted for change in age, height, weight,
      and physical activity; p < 0.05). This provides the first evidence of a sustained
      effect on total hip BMC from short-term high-impact exercise undertaken in early
      childhood. If the benefits are sustained into young adulthood, effectively
      increasing peak bone mass, fracture risk in the later years could be reduced.

PMID- 18072875
TI  - BMD decreases over the course of a year in competitive male cyclists.
AB  - Male cyclists have been found to have low BMD in cross-sectional studies. Changes
      in BMD values over 1 yr of training and competition were studied in 14 male
      cyclists. BMD decreased significantly at the total hip, neck, trochanter, and
      shaft regions but not the lumbar spine. This first prospective study of cyclists
      showed a decrease in BMD over the course of 1 yr. INTRODUCTION: Cross-sectional
      studies have shown that some endurance athletes, and cyclists in particular, have
      low BMD. Whether vigorous cycle training is causally related with low BMD remains
      unknown. MATERIALS AND METHODS: Changes in BMD values over 1 yr of training and
      competition were studied in 14 male road cyclists, 27-44 yr of age. Subjects were
      randomized to receive 1500 (500 mg with meals) or 250 mg of supplemental calcium
      citrate daily. BMD measurements were obtained at pre-, mid-, post-, and off
      season time points over 1 yr. Dermal calcium loss during exercise was estimated
      using a patch collection technique to examine calcium loss as a potential
      mediator of changes in BMD. RESULTS: Using paired t-tests, BMD was found to
      decrease significantly from pre- to off-season at the total hip, neck, shaft, and
      trochanter regions (relative changes of -1.5 +/- 2.1%, -0.7 +/- 2.1%, -0.9 +/-
      2.1%, and -1.0 +/- 1.2%, respectively, all p < 0.05). The 1.0 +/- 1.2% decrease
      in BMD at the lumbar spine failed to reach statistical significance (p = 0.079).
      There were no differences in changes in BMD between the calcium supplementation
      groups. The 2-h dermal calcium loss was estimated at 136.5 +/- 60.5 mg. Higher
      dermal calcium losses were associated with lower baseline BMD values at the total
      hip, neck, and shaft (all p < 0.05), but were not significantly associated with
      changes in BMD. CONCLUSIONS: This study suggests that high intensity cycle
      training may adversely affect BMD. Excessive dermal calcium loss during exercise
      may be a contributing factor, but mechanisms remain to be elucidated.

PMID- 18072876
TI  - Genetic and environmental influence on structural strength of weight-bearing and
      non-weight-bearing bone: a twin study.
AB  - A bivariate genetic analysis among 217 older female twin pairs showed that,
      although the structural strength of tibia and radius are mainly regulated by same
      genetic and environmental factors, the tibia is more affected by environment.
      INTRODUCTION: The habitual loading environment of the bone may modulate the
      relative contribution of genetic and environmental factors to bone structure. The
      purpose of this study was to estimate the contribution of the common and site
      specific genetic and environmental factors to interindividual variation in
      compressive structural strength of the weight-bearing tibia and non-weight
      bearing radius. MATERIALS AND METHODS: pQCT scans were obtained from both members
      of 103 monozygotic (MZ) and 114 dizygotic (DZ) 63- to 76-yr-old female twin pairs
      to estimate the compressive strength of the distal tibia and distal radius.
      Quantitative genetic models were used to decompose the phenotypic variance into
      additive genetic, shared environmental, and individual environmental effects at
      each bone site and to study whether these bone sites share genetic or
      environmental effects. RESULTS: The MZ and DZ twins did not differ in mean age,
      height, weight, or bone structural strength. The age-adjusted Cholesky model
      showed that additive genetic factors accounted for 83% (95% CI, 77-88%) of the
      variance in radial strength and 61% (95% CI, 52-69%) of the variance in tibial
      strength, and these were fully correlated. A shared environmental factor
      accounted for 15% (95% CI, 10-20%) of tibial strength. An individual
      environmental factor accounted for 17% (95% CI, 12-23%) of the variance in radial
      strength and 10% (95% CI, 5-17%) of the variance in tibial strength. The relative
      contribution of an individual environmental factor specific to tibial strength
      was 14% (95% CI, 11-18%). CONCLUSIONS: The results suggest that, in older women,
      the majority of the individual differences in the compressive structural strength
      of the forearm and leg are regulated by genetic and environmental factors that
      are common to both bone sites. However, the relative importance of environmental
      factors was greater for the weight-bearing tibia than for the non-weight-bearing
      radius. Thus, the heritability of bone strength seems to vary between skeletal
      sites according to differences in the typical loading environment.

PMID- 18072878
TI  - Long-term protective effects of zoledronic acid on cancellous and cortical bone
      in the ovariectomized rat.
AB  - Current bisphosphonate therapies effectively prevent bone loss in postmenopausal
      women. We studied the effect of a single intravenous dose of ZOL in
      ovariectomized rats. Protection from bone loss was dose dependent, lasting for up
      to 32 weeks, supporting the rationale for an annual intravenous dosing regimen of
      ZOL for treatment of postmenopausal osteoporosis. INTRODUCTION: Once-yearly
      dosing with zoledronic acid (ZOL) 5 mg can increase BMD and reduce fracture rate
      in postmenopausal women with low BMD. The primary objective of this study was to
      determine the duration of bone protective effects of a single dose of ZOL in
      ovariectomized rats, an animal model of postmenopausal osteopenia. Secondary
      objectives were to determine the effects on bone turnover and mechanical
      properties. MATERIALS AND METHODS: Female Wistar rats (10 per group) received
      single intravenous doses of ZOL 0.8, 4, 20, 100, or 500 microg/kg, alendronate
      200 microg/kg, or isotonic saline 4 days before bilateral ovariectomy. Sham
      operated controls were pretreated with saline. Mass and density of cancellous and
      cortical bone (pQCT) were measured at 4-wk intervals for 32 wk. Bone architecture
      (microCT), bone formation dynamics (fluorochrome label-based histomorphometry),
      and biomechanical strength in compression testing were also assessed at 32 wk.
      RESULTS: Ovariectomy-associated BMD loss was significantly attenuated for 32 wk
      by ZOL >or=4 microg/kg for total BMD, ZOL >or=20 microg/kg for cortical BMD, and
      ZOL >or=4 microg/kg for cancellous BMD (p < 0.01 versus ovariectomized controls).
      Alendronate 200 microg/kg was of equivalent potency to ZOL 20 microg/kg.
      Ovariectomy-associated decreases in trabecular architectural parameters were dose
      dependently attenuated by ZOL. Alendronate 200 microg/kg was equivalent to ZOL 20
      microg/kg. The bone resorption marker TRACP5b indicated transient suppression of
      elevated osteoclast activity by ZOL relative to OVX-rats even at the lowest dose
      of 0.8 microg/kg, whereas at 100-500 microg/kg, the effect was significant
      relative to the OVX control for the entire duration of the study of 32 wk. Bone
      formation parameters were not significantly affected by ZOL 20 microg/kg but were
      significantly reduced by ZOL 100-500 microg/kg. Alendronate 200 microg/kg was
      equivalent to ZOL 100 microg/kg. ZOL produced dose-related improvements in bone
      strength parameters after ovariectomy. Alendronate 200 microg/kg was of similar
      potency to ZOL 20 microg/kg. CONCLUSIONS: The duration and magnitude of the bone
      protecting effect of a single intravenous dose of ZOL in ovariectomized rats is
      dose dependent and lasts for up to 32 wk. Compared with alendronate, ZOL shows 10
      fold higher potency in preventing bone loss. These data support the use of an
      annual intravenous ZOL dosing regimen for the treatment of osteoporosis.

PMID- 18072879
TI  - Notochordal inclusions in the vertebral bone marrow.
AB  - Nontumoral notochordal inclusions in vertebral bone marrow give rise to MRI
      detectable lesion without osteolysis, and their detection may cause concern or
      overtreatment. These lesions likely arise from dislocation of notochordal cells
      from the nucleus pulposus early in life, followed by growth in a permissive bone
      marrow microenvironment. We present a case of nontumoral notochordal inclusions
      in vertebral bone marrow, giving rise to an MRI detectable lesion without
      osteolysis. MRI detection of such lesions may cause concern or overtreatment.
      Quite distinct from chordomas, these lesions likely arise from dislocation of
      notochordal cells from the nucleus pulposus early in life, followed by growth in
      a permissive bone marrow microenvironment.

PMID- 18072883
TI  - Can I have volunteers to die tomorrow?

PMID- 18072882
TI  - Fusion and regenerative therapies: is immortality really recessive?
AB  - Harnessing cellular fusion as a potential tool for regenerative therapy has been
      under tentative investigation for decades. A look back the history of fusion
      experiments in gerontology reveals that whereas some studies indicate that aging
      related changes are conserved in fused cells, others have demonstrated that
      fusion can be used as a tool to revoke cellular senescence and induce tissue
      regeneration. Recent findings about the role of fusion processes in tissue
      homeostasis, replenishment, and repair link insights from fusion studies of
      previous decades with modern developments in stem cell biology and regenerative
      medicine. We suggest that age-associated loss of regenerative capacity is
      associated with a decline of effectiveness in stem cell fusion. We project how
      studies into the fusion of stem cells with tissue cells, or the fusion between
      activator stem cells and patient cells might help in the development of
      applications that "rejuvenate" certain target cells, thereby strategically
      reinstating a regeneration cascade. The outlook is concluded with a discussion of
      the next research milestones and the potential hazards of fusion therapies.

PMID- 18072880
TI  - Impact of glucose-dependent insulinotropic peptide on age-induced bone loss.
AB  - GIP is an important hormonal link between nutrition and bone formation. We show
      for the first time that BMSCs express functional GIP receptors, that expression
      decreases with aging, and that elevations in GIP can prevent age-associated bone
      loss. INTRODUCTION: We previously showed that C57BL/6 mice lose bone mass as they
      age, particularly between 18 and 24 mo of age. The mechanisms involved in this
      age-dependent induced bone loss are probably multifactorial, but adequate
      nutrition and nutritional signals seem to be important. Glucose-dependent
      insulinotropic peptide (GIP) is an enteric hormone whose receptors are present in
      osteoblasts, and GIP is known to stimulate osteoblastic activity in vitro. In
      vivo, GIP-overexpressing C57BL/6 transgenic (GIP Tg(+)) mice have increased bone
      mass compared with controls. Bone histomorphometric data suggest that GIP
      increases osteoblast number, possibly by preventing osteoblastic apoptosis.
      However, potential GIP effects on osteoblastic precursors, bone marrow stromal
      cells (BMSCs), had not previously been examined. In addition, effects of GIP on
      age-induced bone loss were not known. MATERIALS AND METHODS: Changes in BMD,
      biomechanics, biomarkers of bone turnover, and bone histology were assessed in
      C57BL/6 GIP Tg(+) versus Tg(-) (littermate) mice between the ages of 1 and 24 mo
      of age. In addition, age-related changes in GIP receptor (GIPR) expression and
      GIP effects on differentiation of BMSCs were also assessed as potential causal
      factors in aging-induced bone loss. RESULTS: We report that bone mass and bone
      strength in GIP Tg(+) mice did not drop in a similar age-dependent fashion as in
      controls. In addition, biomarker measurements showed that GIP Tg(+) mice had
      increased osteoblastic activity compared with wildtype control mice. Finally, we
      report for the first time that BMSCs express GIPR, that the expression decreases
      in an age-dependent manner, and that stimulation of BMSCs with GIP led to
      increased osteoblastic differentiation. CONCLUSIONS: Our data show that elevated
      GIP levels prevent age-related loss of bone mass and bone strength and suggest
      that age-related decreases in GIP receptor expression in BMSCs may play a
      pathophysiological role in this bone loss. We conclude that elevations in GIP may
      be an effective countermeasure to age-induced bone loss.

PMID- 18072885
TI  - Validated supercentenarian cases aged 114 and above.

PMID- 18072884
TI  - Theoretical paper: exploring overlooked natural mitochondria-rejuvenative
      intervention: the puzzle of bowhead whales and naked mole rats.
AB  - There is an imperative need for exploring and implementing mitochondria
      rejuvenative interventions that can bridge the current gap toward the step-by
      step realization of strategies for engineered negligible senescence (SENS)
      agenda. Recently discovered in mammals, natural mechanism mitoptosis-a selective
      "suicide" of mutated mitochondria-can facilitate continuous purification of
      mitochondrial pool in an organism from the most reactive oxygen species (ROS)
      producing mitochondria. Mitoptosis, which is considered to be the first stage of
      ROS-induced apoptosis, underlies follicular atresia (a "quality control"
      mechanism in female germline cells that eliminates most germinal follicles in
      female embryos). Mitoptosis can be also activated in adult postmitotic somatic
      cells by evolutionary conserved phenotypic adaptations to intermittent oxygen
      restriction (IOR) and synergistically acting intermittent caloric restriction
      (ICR). IOR and ICR are common in mammals and seem to underlie extraordinary
      longevity and augmented cancer resistance in bowhead whales (Balena mysticetus)
      and naked mole rats (Heterocephalus glaber). Furthermore, in mammals IOR can
      facilitate continuous stromal stem cells-de-pendent tissue repair. A comparative
      analysis of IOR and ICR mechanisms in both mammals, in conjunction with the
      experience of decades of biomedical and clinical research on emerging
      preventative, therapeutic, and rehabilitative modality-the intermittent hypoxic
      training/therapy (IHT)-indicates that the notable clinical efficiency of IHT is
      based on the universal adaptational mechanisms that are common in mammals.
      Further exploration of natural mitochondria-preserving and -rejuvenating
      strategies can help refinement of IOR- and ICR-based synergistic protocols,
      having value in clinical human rejuvenation.

PMID- 18072886
TI  - It's time for change and resolve.

PMID- 18072887
TI  - The first 100 days: an open letter to the new Minister for Health.

PMID- 18072888
TI  - 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and
      Prevention.

PMID- 18072889
TI  - The Northern Territory emergency response: a chance to heal Australia's worst
      sore.

PMID- 18072890
TI  - The Aboriginal Medical Services Alliance Northern Territory: engaging with the
      intervention to improve primary health care.

PMID- 18072891
TI  - Protecting little children's health--or not?

PMID- 18072893
TI  - Emergency department overcrowding: dying to get in?

PMID- 18072892
TI  - The Northern Territory intervention: voices from the centre of the fringe.

PMID- 18072894
TI  - Characteristics and outcomes of patients who "did not wait" after attending Perth
      public hospital emergency departments, 2000-2003.
AB  - OBJECTIVE: To determine characteristics and outcomes of patients who did not wait
      to see a doctor in emergency departments (EDs). DESIGN AND SETTING: Population
      based outcome study using probabilistically linked ED and Western Australian
      death records, with ED records from all seven Perth public hospitals that have
      EDs from 1 July 2000 to 30 June 2003. MAIN OUTCOME MEASURES: Rates of "did not
      wait" (DNW) presentations, overall and for individual hospitals; characteristics
      of DNW patients; mortality rates among DNW patients at 2, 7 and 30 days. RESULTS:
      DNW rates varied from 2.6% to 6.3% (average, 4.1%) and were generally lower in
      tertiary teaching hospitals. DNW patients had conditions of lower urgency,
      predominantly Australasian Triage Scale category 4 (67.1%) and 5 (23.4%). The DNW
      rates in these categories were 5.8% and 10.6%, respectively (P < 0.001). Patients
      referred by health care providers had lower DNW rates (0.5%; P < 0.001). DNW
      patients were more frequently male (4.4% v 3.8%; P < 0.001), and young to middle
      aged adults (15-44 years; 5.8%; P < 0.001). Patients with a higher than average
      DNW rate were more likely to arrive by private transport (5.0%; P < 0.001) or
      with police (5.8%; P < 0.001), re-present for review (8.6%; P < 0.001) or have
      social or behavioural problems (7.7%; P < 0.001). Most patients (91.9%) did not
      wait on only one occasion. The 30-day mortality rate among DNW patients was
      significantly lower than for patients seen by a doctor and discharged (0.14 v
      0.20%; P = 0.026), and for all patients seen in the ED (1.28%; P < 0.001).
      CONCLUSIONS: Patients who did not wait for medical assessment in Perth EDs had
      conditions of lower acuity and had lower mortality rates than those who waited
      for assessment.

PMID- 18072895
TI  - The colonoscope strikes back: a diverticular Darth Vader.

PMID- 18072896
TI  - Deck the halls with rows of trolleys...emergency departments are busiest over the
      Christmas holiday period.
AB  - OBJECTIVES: To assess changes in emergency department (ED) activity and visits to
      EDs that could have been managed by general practitioners (GP-type visits) in the
      Christmas and New Year holiday period compared with the rest of the year. DESIGN
      AND SETTING: Retrospective descriptive and analytical comparison of New South
      Wales ED visits in the holiday period and the rest of the year; data were
      obtained from the NSW Emergency Department Data Collection database for the
      period 2001 to early 2006. More detailed information in 2005-2006 allowed GP-type
      visits to be assessed in this period only. MAIN OUTCOME MEASURES: The change in
      the number and percentage of weekly ED visits during the holiday period. RESULTS:
      Between 2001 and 2006, average weekly counts of ED visits increased by 9% (95%
      CI, 7%-11%) during the holiday period. The holiday increase was largely accounted
      for by visits that were less urgent, and for patients who were not admitted, did
      not arrive by ambulance, had a shorter treatment time and arrived between 08:00
      and midnight. In 2005-2006, average weekly counts of GP-type visits increased by
      21% (95% CI, 15%-28%) compared with 8% (95% CI, 4%-12%) for ED visits overall.
      However, GP-type visits accounted for only 39% of the additional holiday visits.
      GP-type visits increased mainly for adults and more in urban than rural areas.
      CONCLUSIONS: The Christmas and New Year period is the busiest time of year for
      NSW EDs. However, only some of the additional holiday visits can be attributed to
      GP-type visits. Improving access to GPs, but also to broader hospital and
      community-based health care services over the holiday period, should be
      considered for managing the excess demand.

PMID- 18072897
TI  - Inside the emergency department.

PMID- 18072898
TI  - Cardiac arrest and chewing gum--an unfortunate combination.

PMID- 18072899
TI  - Health care down the drain.

PMID- 18072900
TI  - Sharing the secrets of success: conversations with the Medical Journal of
      Australia/Wyeth Research Award winners, 1995-2006.

PMID- 18072901
TI  - "Australian" lymphoma.

PMID- 18072902
TI  - The forgotten successes and sacrifices of Charles Kellaway, director of the
      Walter and Eliza Hall Institute, 1923-1944.
AB  - Charles Halliley Kellaway (1889-1952) was one of the first Australians to make a
      full-time career of medical research. He built his scientific reputation on
      studies of snake venoms and anaphylaxis. Under Kellaway's directorship, the
      Walter and Eliza Hall Institute gained worldwide acclaim, and he played a
      critical role in its success between the world wars. His administrative and
      financial strategies in the era before the National Health and Medical Research
      Council (NHMRC) helped local medical research weather the Depression and gain a
      strong foothold by World War II.

PMID- 18072903
TI  - A beginner's guide to criticism.

PMID- 18072904
TI  - On the breeding of coauthors: just call me Al.

PMID- 18072906
TI  - The Oxford Health Alliance: a risky business?

PMID- 18072907
TI  - What are governments for?

PMID- 18072908
TI  - Is caffeine in soft drinks really necessary?

PMID- 18072909
TI  - Can food and beverage companies help improve population health? Some insights
      from PepsiCo.

PMID- 18072910
TI  - The way we live in our cities.
AB  - During 2007, the human species became predominantly urban. Australia is highly
      urbanised, and health varies within Australian cities. Australian urban life is
      characterised by sedentariness, excess food intake, reliance on cars for
      transport, a high level of exposure to media and marketing messages, and a
      consumer culture. These characteristics are linked to obesity, diabetes, heart
      disease, some cancers, chronic respiratory disease, injury, depression and
      anxiety. The evolution of cities has been characterised as a four-stage process:
      poverty, industrial, consumption and eco-city. Each stage but the last has
      defining health disorders. Transition to healthy and sustainable cities requires
      infrastructure investment in new urban areas (including mass transit, education
      and health services), better conditions for walking and cycling, access to
      healthy food and encouragement of suburban economic development. There is a role
      for everyone in the transition to healthy and sustainable cities.

PMID- 18072911
TI  - Morbidity and mortality during heatwaves in metropolitan Adelaide.
AB  - OBJECTIVE: To investigate morbidity and mortality associated with heatwaves in
      metropolitan Adelaide using ambulance, hospital admission, and mortality data.
      DESIGN, PARTICIPANTS AND SETTING: Case-series study comparing health risks in the
      Adelaide metropolitan population during heatwaves and non-heatwave periods. MAIN
      OUTCOME MEASURES: Daily observations for ambulance transports (1993-2006),
      hospital admissions (1993-2006), and mortality (1993-2004), categorised using
      International classification of diseases (ninth and tenth revisions) codes for
      the relevant disease groups. RESULTS: During heatwaves, total ambulance transport
      increased by 4% (95% CI, 1%-7%), including significant assault-related increases
      for people aged 15-64 years. Reductions were observed in relation to cardiac,
      sports- and falls-related events. Total hospital admissions increased by 7% (95%
      CI, - 1% to 16%). Total mental health admissions increased by 7% (95% CI, 1%
      13%), and total renal admissions by 13% (95% CI, 3%-25%). Ischaemic heart disease
      admissions increased by 8% (95% CI, 1%-15%) among people aged 65-74 years. Total
      mortality, disease- and age-specific mortality did not increase, apart from a
      small increase in mental health-related mortality in people aged 65-74 years.
      Significant decreases were observed in cardiovascular-related mortality.
      CONCLUSION: In contrast to evidence from extreme heatwaves in the northern
      hemisphere, we found no excess mortality during heatwaves in metropolitan
      Adelaide, perhaps because of adaptive behaviour to regular hot weather spells.
      Projected temperature increases and evidence of modest increases in morbidity
      during heatwaves indicate the need for a heatwave response plan for Adelaide.

PMID- 18072912
TI  - Arthroplasty tourism.
AB  - The practice of "medical tourism" is gaining popularity. Lower costs and shorter
      waiting times are compelling motivating factors. There are also increasing
      commercial interests promoting medical tourism. There are very limited clinical
      data to support or refute this practice. However, medical tourism breaks
      important elements in the traditional health care model, including patient
      selection, continuity of care, and practice auditing. When complications arise,
      challenges specific to medical tourism patients may be encountered.

PMID- 18072913
TI  - Personal carbon trading: a potential "stealth intervention" for obesity
      reduction?

PMID- 18072914
TI  - Ingredient and nutrition information labelling of alcoholic beverages: do
      consumers want it?

PMID- 18072915
TI  - Mitigating the health impacts of a natural disaster--the June 2007 long-weekend
      storm in the Hunter region of New South Wales.
AB  - A severe storm that began on Thursday, 7 June 2007 brought heavy rains and gale
      force winds to Newcastle, Gosford, Wyong, Sydney, and the Hunter Valley region of
      New South Wales. The storm caused widespread flooding and damage to houses,
      businesses, schools and health care facilities, and damaged critical
      infrastructure. Ten people died as a result of the storm, and approximately 6000
      residents were evacuated. A natural disaster was declared in 19 local government
      areas, with damage expected to reach $1.5 billion. Additional demands were made
      on clinical health services, and interruption of the electricity supply to over
      200,000 homes and businesses, interruption of water and gas supplies, and
      sewerage system pump failures presented substantial public health threats. A
      public health emergency operations centre was established by the Hunter New
      England Area Health Service to coordinate surveillance activities, respond to
      acute public health issues and prevent disease outbreaks. Public health
      activities focused on providing advice, cooperating with emergency service
      agencies, monitoring water quality and availability, preventing illness from
      sewage-contaminated flood water, assessing environmental health risks,
      coordinating the local government public health response, and surveillance for
      storm-related illness and disease outbreaks, including gastroenteritis. The local
      ABC (Australian Broadcasting Corporation) radio station played a key role in
      disseminating public health advice. A household survey conducted within a
      fortnight of the storm established that household preparedness and storm warning
      systems could be improved.

PMID- 18072916
TI  - A food "lifeboat": food and nutrition considerations in the event of a pandemic
      or other catastrophe.
AB  - Influenza pandemics are a real risk and are best managed by self-isolation and
      social distancing to reduce the risk of infection and spread. Such isolation
      depends on availability of food of adequate quantity and quality. Australia has
      one of the most concentrated food supplies of any country, making rapid food
      depletion more likely in a crisis. Food stockpiling by both authorities and
      citizens is an important safety precaution that should be given greater media
      coverage. Food and nutrition guidelines are provided for survival rations in the
      event of a pandemic or other catastrophe.

PMID- 18072917
TI  - Hospital pandemic preparedness: health care workers' opinions on working during a
      pandemic.

PMID- 18072918
TI  - The deaf and doctors: a Shepherd's two flocks.

PMID- 18072919
TI  - Reaching out with a hand of help.

PMID- 18072920
TI  - Peer review: where science meets the arts of war, politics and ancient history.

PMID- 18072921
TI  - Education programs at the new Australian School of Advanced Medicine at Macquarie
      University.
AB  - The Australian School of Advanced Medicine at Macquarie University, Sydney, will
      provide competency-based university medical specialist training in a private
      hospital environment, Australia. The rationale is the need for additional and
      innovative programs to meet emerging demands, and alternative training programs
      to increase the opportunities for doctors to achieve their career goals. The
      programs will focus on learning (not teaching), on developing a comprehensive set
      of professional competencies, on teamwork, and on research. Special features of
      the programs include: the potential for scholars to progress at a variable pace;
      the use of facilities for simulation and practice; and rigorous evaluation. The
      school is developing strong linkages with other institutions, nationally and
      internationally. Challenges include the recruitment of fee-paying trainees; the
      time commitment required of faculty members; a reliable and bias-free assessment
      system; and ethical concerns about undertaking training activities on private
      patients.

PMID- 18072922
TI  - Medical specialist education and training in Australia.

PMID- 18072923
TI  - Patient privacy and Latin.

PMID- 18072924
TI  - Snow--at Christmas.

PMID- 18072926
TI  - An outbreak of illness in poultry and humans in 16th century Indonesia.

PMID- 18072925
TI  - Clinical examination is still good: suck it and see.

PMID- 18072927
TI  - Recently in the emergency department: chest x-ray of a repeatedly resuscitated
      object.

PMID- 18072928
TI  - Doctors in satirical prints and cartoons.

PMID- 18072929
TI  - We three kings and Christmas trees: pharmacotherapy from presents and diseases
      from decorations.

PMID- 18072930
TI  - Teaching Tamil tigers.

PMID- 18072931
TI  - The fight for a life-saving drug: a personal perspective.

PMID- 18072932
TI  - A starry sky in the brain.

PMID- 18072933
TI  - From the diary of a novice physician.

PMID- 18072934
TI  - Matrix metalloproteinase-3 induction in rat brain astrocytes: focus on the role
      of two AP-1 elements.
AB  - Many brain cells secrete MMPs (matrix metalloproteinases), and increased or
      misregulated MMP levels are found in neurodegenerative disorders. Here we report
      that MMP-3 transcription and protein secretion were increased in rat brain
      astrocytes stimulated with lipopolysaccharide, gangliosides or interferon-gamma.
      Sequential deletion of the MMP-3 promoter revealed that sequences between -0.5 kb
      and the start codon were crucial for the transcriptional induction of MMP-3. In
      addition, experiments using pharmacological inhibitors of individual mitogen
      activated protein kinases revealed that MMP-3 induction and promoter activity
      involved Jun N-terminal kinase, a representative upstream signal of AP-1
      (activator protein-1). Sequence analyses of the region of the MMP-3 promoter 500
      bp from the start codon indicated the presence of three AP-1 binding sequences.
      Among them, electrophoretic-mobility-shift assays as well as site-directed
      mutagenesis of individual AP-1 sequences revealed that distal and middle, but not
      proximal, sequences largely mediated its induction. Together, these results
      indicate that AP-1 could control MMP-3 induction in brain astrocytes and that its
      regulation through specific AP-1 elements could be exploited in the treatment of
      brain pathologies in which increased expression of MMP-3 plays crucial roles.

PMID- 18072935
TI  - A conserved hydrogen-bond network in the catalytic centre of animal glutaminyl
      cyclases is critical for catalysis.
AB  - QCs (glutaminyl cyclases; glutaminyl-peptide cyclotransferases, EC 2.3.2.5)
      catalyse N-terminal pyroglutamate formation in numerous bioactive peptides and
      proteins. The enzymes were reported to be involved in several pathological
      conditions such as amyloidotic disease, osteoporosis, rheumatoid arthritis and
      melanoma. The crystal structure of human QC revealed an unusual H-bond (hydrogen
      bond) network in the active site, formed by several highly conserved residues
      (Ser(160), Glu(201), Asp(248), Asp(305) and His(319)), within which Glu(201) and
      Asp(248) were found to bind to substrate. In the present study we combined steady
      state enzyme kinetic and X-ray structural analyses of 11 single-mutation human
      QCs to investigate the roles of the H-bond network in catalysis. Our results
      showed that disrupting one or both of the central H-bonds, i.e.,
      Glu(201)...Asp(305) and Asp(248)...Asp(305), reduced the steady-state catalysis
      dramatically. The roles of these two COOH...COOH bonds on catalysis could be
      partly replaced by COOH...water bonds, but not by COOH...CONH(2) bonds,
      reminiscent of the low-barrier Asp...Asp H-bond in the active site of pepsin-like
      aspartic peptidases. Mutations on Asp(305), a residue located at the centre of
      the H-bond network, raised the K(m) value of the enzyme by 4.4-19-fold, but
      decreased the k(cat) value by 79-2842-fold, indicating that Asp(305) primarily
      plays a catalytic role. In addition, results from mutational studies on Ser(160)
      and His(319) suggest that these two residues might help to stabilize the
      conformations of Asp(248) and Asp(305) respectively. These data allow us to
      propose an essential proton transfer between Glu(201), Asp(305) and Asp(248)
      during the catalysis by animal QCs.

PMID- 18072936
TI  - A xyloglucan-specific family 12 glycosyl hydrolase from Aspergillus niger:
      recombinant expression, purification and characterization.
AB  - A new GH12 (glycosyl hydrolase 12) family XEG [xyloglucan-specific endo-beta-1,4
      glucanase (EC 3.2.1.151)] from Aspergillus niger, AnXEG12A, was overexpressed,
      purified and characterized. Whereas seven xyloglucanases from GH74 and two
      xyloglucanases from GH5 have been characterized previously, this is only the
      third characterized example of a GH12 family xyloglucanase. GH12 enzymes are
      structurally and mechanistically distinct from GH74 enzymes. Although over 100
      GH12 sequences are now available, little is known about the structural and
      biochemical bases of xyloglucan binding and hydrolysis by GH12 enzymes.
      Comparison of the AnXEG12A cDNA sequence with the genome sequence of A. niger
      showed the presence of two introns, one in the coding region and the second one
      in the 333-nt-long 3'-untranslated region of the transcript. The enzyme was
      expressed recombinantly in A. niger and was readily purified from the culture
      supernatant. The isolated enzyme appeared to have been processed by a kexin-type
      protease, which removed a short prosequence. The substrate specificity was
      restricted to xyloglucan, with cleavage at unbranched glucose in the backbone.
      The apparent kinetic parameters were similar to those reported for other
      xyloglucan-degrading endoglucanases. The pH optimum (5.0) and temperature
      resulting in highest enzyme activity (50-60 degrees C) were higher than those
      reported for a GH12 family xyloglucanase from Aspergillus aculeatus, but similar
      to those of cellulose-specific endoglucanases from the GH12 family. Phylogenetic,
      sequence and structural comparisons of GH12 family endoglucanases helped to
      delineate features that appear to be correlated to xyloglucan specificity.

PMID- 18072937
TI  - Negative regulation of cell-cycle progression by RINGO/Speedy E.
AB  - Cell-cycle transitions are controlled by CDKs (cyclin-dependent kinases), whose
      activation is usually associated with the binding of cyclins. RINGO/Speedy
      proteins can also bind to and activate CDKs, although they do not have amino acid
      sequence homology with cyclins. The RINGO/Speedy family members studied so far
      positively regulate cell-cycle progression. In the present paper, we report the
      biochemical and functional characterization of RINGO/Speedy E. We show that
      RINGO/Speedy E is a functionally distant member of this protein family that
      negatively affects cell-cycle progression. RINGO/Speedy E overexpression inhibits
      the meiotic progression in Xenopus oocytes as well as the proliferation of
      mammalian cells. RINGO/Speedy E can bind to endogenous CDK1 and CDK2 in both
      cellular systems. However, the RINGO/Speedy E-activated CDKs have different
      substrate specificity than the CDKs activated by other RINGO/Speedy proteins,
      which may account for their different effects on the cell cycle. Our results
      indicate that, although all RINGO/Speedy family members can activate CDKs, they
      may differently regulate cell-cycle progression.

PMID- 18072938
TI  - Sequential regulation of ferroportin expression after erythrophagocytosis in
      murine macrophages: early mRNA induction by haem, followed by iron-dependent
      protein expression.
AB  - Tissue macrophages play an essential role in iron recycling through the
      phagocytosis of senescent RBCs (red blood cells). Following haem catabolism by
      HO1 (haem oxygenase 1), they recycle iron back into the plasma through the iron
      exporter Fpn (ferroportin). We previously described a cellular model of EP
      (erythrophagocytosis), based on primary cultures of mouse BMDMs (bone-marrow
      derived macrophages) and aged murine RBCs, and showed that EP induces changes in
      the expression profiles of Fpn and HO1. In the present paper, we demonstrate that
      haem derived from human or murine RBCs or from an exogenous source of haem led to
      marked transcriptional activation of the Fpn and HO1 genes. Iron released from
      haem catabolism subsequently stimulated the Fpn mRNA and protein expression
      associated with localization of the transporter at the cell surface, which
      probably promotes the export of iron into the plasma. These findings highlight a
      dual mechanism of Fpn regulation in BMDMs, characterized by early induction of
      the gene transcription predominantly mediated by haem, followed by iron-mediated
      post-transcriptional regulation of the exporter.

PMID- 18072939
TI  - Exploring the complex world of RNA regulation.

PMID- 18072940
TI  - Purine sensing by riboswitches.
AB  - Structured mRNA elements called riboswitches control gene expression by binding
      to small metabolites. Over a dozen riboswitch classes have been characterized
      that target a broad range of molecules and vary widely in size and secondary
      structure. Four of the known riboswitch classes recognize purines or modified
      purines. Three of these classes are closely related in conserved sequence and
      secondary structure, but members of these classes selectively recognize guanine,
      adenine or 2'-deoxyguanosine. Members of the fourth riboswitch class adopt a
      distinct structure to form a selective binding pocket for the guanine analogue
      preQ(1) (7-aminomethyl-7-deazaguanine). All four classes of purine-sensing
      riboswitches are most likely to recognize their respective metabolites by
      utilizing a riboswitch residue to make a canonical Watson-Crick base-pair with
      the ligand. This review will provide a summary of the purine-sensing
      riboswitches, as well as discuss the complex functions and applications of these
      RNAs.

PMID- 18072941
TI  - RNA silencing movement in plants.
AB  - Higher eukaryotes have developed a mechanism of sequence-specific RNA degradation
      which is known as RNA silencing. In plants and some animals, similar to the
      nematode Caenorhabditis elegans, RNA silencing is a non-cell-autonomous event.
      Hence, silencing initiation in one or a few cells leads progressively to the
      sequence-specific suppression of homologous sequences in neighbouring cells in an
      RNA-mediated fashion. Spreading of silencing in plants occurs through
      plasmodesmata and results from a cell-to-cell movement of a short-range silencing
      signal, most probably 21-nt siRNAs (short interfering RNAs) that are produced by
      one of the plant Dicer enzymes. In addition, silencing spreads systemically
      through the phloem system of the plants, which also translocates metabolites from
      source to sink tissues. Unlike the short-range silencing signal, there is little
      known about the mediators of systemic silencing. Recent studies have revealed
      various and sometimes surprising genetic elements of the short-range silencing
      spread pathway, elucidating several aspects of the processes involved. In this
      review we attempt to clarify commonalities and differences between the individual
      silencing pathways of RNA silencing spread in plants.

PMID- 18072942
TI  - Re-programming of translation following cell stress allows IRES-mediated
      translation to predominate.
AB  - There is now an overwhelming body of evidence to suggest that internal ribosome
      entry is required to maintain the expression of specific proteins during patho
      physiological situations when cap-dependent translation is compromised, for
      example, following heat shock or during mitosis, hypoxia, differentiation and
      apoptosis. Translational profiling has been used by several groups to assess the
      extent to which alternative mechanisms of translation initiation selectively
      recruit mRNAs to polysomes during cell stress. The data from these studies have
      shown that under each condition 3-5% of coding mRNAs remain associated with the
      polysomes. Importantly, the genes identified in each of these studies do not show
      a significant amount of overlap, suggesting that 10-15% of all mRNAs have the
      capability for their initiation to occur via alternative mechanism(s).

PMID- 18072943
TI  - Building up the inactive X chromosome.
AB  - The compensation of the different level of transcripts of X-linked genes in male
      and female mammals is achieved through X chromosome inactivation, a complex
      process that differentially regulates the sex chromosomes of female cells. This
      mechanism has been dissected at evolutionary, genetic and molecular levels: here,
      we discuss some of the latest examples that illustrate better these intricate
      connections, focusing particularly on the emerging role of spatial and three
      dimensional chromatin arrangements in the building of this special chromosome,
      the inactive X chromosome.

PMID- 18072944
TI  - Structural and functional consequences of the replacement of proximal residues
      Cys(172) and Cys(192) in the large subunit of ribulose-1,5-bisphosphate
      carboxylase/oxygenase from Chlamydomonas reinhardtii.
AB  - Proximal Cys(172) and Cys(192) in the large subunit of the photosynthetic enzyme
      Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase; EC 4.1.1.39) are
      evolutionarily conserved among cyanobacteria, algae and higher plants. Mutation
      of Cys(172) has been shown to affect the redox properties of Rubisco in vitro and
      to delay the degradation of the enzyme in vivo under stress conditions. Here, we
      report the effect of the replacement of Cys(172) and Cys(192) by serine on the
      catalytic properties, thermostability and three-dimensional structure of
      Chlamydomonas reinhardtii Rubisco. The most striking effect of the C172S
      substitution was an 11% increase in the specificity factor when compared with the
      wild-type enzyme. The specificity factor of C192S Rubisco was not altered. The
      V(c) (V(max) for carboxylation) was similar to that of wild-type Rubisco in the
      case of the C172S enzyme, but approx. 30% lower for the C192S Rubisco. In
      contrast, the K(m) for CO(2) and O(2) was similar for C192S and wild-type
      enzymes, but distinctly higher (approximately double) for the C172S enzyme. C172S
      Rubisco showed a critical denaturation temperature approx. 2 degrees C lower than
      wild-type Rubisco and a distinctly higher denaturation rate at 55 degrees C,
      whereas C192S Rubisco was only slightly more sensitive to temperature
      denaturation than the wild-type enzyme. X-ray crystal structures reveal that the
      C172S mutation causes a shift of the main-chain backbone atoms of beta-strand 1
      of the alpha/beta-barrel affecting a number of amino acid side chains. This may
      cause the exceptional catalytic features of C172S. In contrast, the C192S
      mutation does not produce similar structural perturbations.

PMID- 18072945
TI  - Post-translational modification and proteolytic processing of urinary
      osteopontin.
AB  - OPN (osteopontin) is a highly phosphorylated glycoprotein present in many tissues
      and body fluids. In urine, OPN is a potent inhibitor of nucleation, growth and
      aggregation of calcium oxalate crystals, suggesting that it has a role in the
      prevention of renal stone formation. The role of OPN in nephrolithiasis is,
      however, somewhat unclear, as it may also be involved in urinary stone formation,
      and it has been identified among the major protein components of renal calculi.
      Most likely, the function of OPN in urine is dependent on the highly anionic
      character of the protein. Besides a very high content of aspartic and glutamic
      residues, OPN is subjected to significant PTM (post-translational modification),
      such as phosphorylation, sulfation and glycosylation, which may function as
      regulatory switches in promotion or inhibition of mineralization. In the present
      study, we have characterized the PTMs of intact human urinary OPN and N-terminal
      fragments thereof. MS analysis showed a mass of 37.7 kDa for the intact protein.
      Enzymatic dephosphorylation and peptide mass analyses demonstrated that the
      protein contains approximately eight phosphate groups distributed over 30
      potential phosphorylation sites. In addition, one sulfated tyrosine and five O
      linked glycosylations were identified in OPN, whereas no N-linked glycans were
      detected. Peptide mapping and immunoblotting using different monoclonal
      antibodies showed that the N-terminal fragments present in urine are generated by
      proteolytic cleavage at Arg(228)-Leu(229) and Tyr(230)-Lys(231).

PMID- 18072960
TI  - Agreement between physicians and parents in rating functional ability of children
      with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate concordance between physicians and parents in rating
      the degree of functional ability of children with juvenile idiopathic arthritis
      (JIA). METHODS: The attending physician and a parent were asked to rate
      independently the level of physical functioning of 155 patients with disease
      duration >/= 5 years on a 6-point scale ranging from 1 = no disability (i.e. the
      child can do without difficulty all activities that children of his/her age can
      do) to 6 = severe disability (i.e. all activities are difficult for the child).
      At study visit, measures of JIA activity and damage were assessed. Agreement was
      evaluated with weighted kappa (<0.40 = poor agreement; 0.41-0.60 = moderate
      agreement; 0.61-0.80 = substantial agreement; >0.80 excellent agreement).
      Physician/parent evaluations were divided in 3 groups: 1) concordance; 2) parent
      over-rating = parent assessment over-rated relative to physician assessment; 3)
      physician over-rating = physician assessment over-rated relative to parent
      assessment. Factors affecting concordance/discordance were evaluated by means of
      Kruskal-Wallis or Chi-square/Fisher exact test. RESULTS: Concordance, parent over
      rating and physician over-rating were observed in 107 (69%), 29 (18.7%) and 19
      (12.3%) evaluations, respectively. Kappa value was 0.69. Parent over-rating was
      associated with greater intensity of pain (p = 0.01) and higher Childhood Health
      Assessment Questionnaire (C-HAQ) score (p = 0.004), whereas physician over-rating
      was associated with more severe joint disease (p = 0.04 to <0.001), higher C
      reactive protein (p = 0.03) higher frequency of Steinbrocker functional class =
      II (p < 0.001), and greater articular damage, as measured with the Juvenile
      Arthritis Damage Index (p < 0.001). CONCLUSION: Physicians and parents revealed
      fair concordance in rating functional ability of children with JIA. Parent over
      rating was associated with greater child's pain and worse C-HAQ score, whereas
      physician over-rating was associated with greater severity of joint inflammation
      and damage.

PMID- 18072961
TI  - Measuring cognitive insight in schizophrenia and bipolar disorder: a comparative
      study.
AB  - BACKGROUND: Beck Cognitive Insight Scale (BCIS) has been designed for assessment
      of self-reflection on patients' anomalous experiences and interpretations of own
      beliefs. The scale has been developed and validated for patients with
      schizophrenia. We wanted to study the utility of the scale for patients with
      bipolar disorder. The relationship between the BCIS as a measure of cognitive
      insight and established methods for assessment of insight of illness was explored
      in both diagnostic groups. METHODS: The BCIS self-report inventory was
      administered to patients with schizophrenia (n = 143), bipolar disorder (n = 92)
      and controls (n = 64). The 15 items of the inventory form two subscales, self
      reflectiveness and self-certainty. RESULTS: The internal consistency of the
      subscales was good for the patient groups and the controls. The mean subscale
      scores were not significantly different for the three groups. Four items in
      subscale self-reflectiveness referring to psychotic experiences gave, however,
      different results in the control subjects. Self-certainty and scores on insight
      item PANSS correlated significantly in the schizophrenia, but not in the bipolar
      group. CONCLUSION: BCIS with its two subscales seems applicable for patients with
      bipolar disorder as well as for patients with schizophrenia. The self-report
      inventory can also be applied to control subjects if the items referring to
      psychotic experiences are omitted. In schizophrenia high scores on self-certainty
      is possibly associated with poor insight of illness. For the bipolar group the
      subscales are largely independent of traditional insight measures.

PMID- 18072962
TI  - Challenges for vaccination in the elderly.
AB  - The increased susceptibility of the elderly to infection presents a major
      challenge to public health services. An aging immune system is well documented as
      the cause of increased infection rates in elderly people. Such immunosenescence
      is multi-factorial and incompletely understood. Immunosenescent changes include
      malfunctioning of innate immune system cellular receptors; involution of the
      thymus, with consequent reduction of the naive T cell population; alteration of
      the T cell population composition; modified phenotypes of individual T cells; and
      replicative senescence of memory cells expressing naive markers. Unfortunately,
      immunosenescence also renders vaccination less effective in the elderly. It is
      therefore important that the vaccines used against common but preventable
      diseases, such as influenza, are specifically enhanced to overcome the reduced
      immune responsiveness of this vulnerable population.

PMID- 18072963
TI  - How useful is the assessment of lymphatic vascular density in oral carcinoma
      prognosis?
AB  - BACKGROUND: Lymphatic vessels are major routes for metastasis in head and neck
      squamous cell carcinoma (HNSCC), but lymphatic endothelial cells (LECs) are
      difficult to recognize in tumor histological sections. D2-40 stains podoplanin, a
      molecule expressed in LECs, however, the potential prognostic usefulness of this
      molecule is not completely understood in HNSCC. We aimed to investigate the value
      of assessing peritumoral and intratumoral lymphatic vessel density (LVD) as
      prognostic marker for HNSCC. METHODS: Thirty-one cases of HNSCC were stained for
      D2-40 and CD31. LVD and blood vessel density (BVD) were assessed by counting
      positive reactions in 10 hotspot areas at x200 magnification. RESULTS: D2-40 was
      specific for lymphatic vessels and did not stain blood vascular endothelial
      cells. LECs showed more tortuous and disorganized structure in intratumoral
      lymphatic vessels than in peritumoral ones. No statistical differences were
      observed between peritumoral-LVD and intratumoral-LVD or between peritumoral-BVD
      and intratumoral-BVD. Tumor D2-40 staining was positively associated with
      lymphatic vessel invasion (p = 0.011). CONCLUSION: LVD is a powerful marker for
      HNSCC prognosis. We found significant differences in peritumoral and intratumoral
      D2-40 immunoreactivity, which could have important implications in future
      therapeutic strategies and outcome evaluation.

PMID- 18072964
TI  - No evidence for association between tau gene haplotypic variants and
      susceptibility to Creutzfeldt-Jakob disease.
AB  - BACKGROUND: A polymorphism at codon 129 of the prion protein gene (PRNP) is the
      only well-known genetic risk factor for Creutzfeldt-Jakob disease (CJD). However,
      there is increasing evidence that other loci outside the PRNP open reading frame
      might play a role in CJD aetiology as well. METHODS: We studied tau protein gene
      (MAPT) haplotypic variations in a population of sporadic and variant CJD
      patients. We tested 6 MAPT haplotype tagging SNPs (htSNPs) in a Dutch population
      based sample of sporadic CJD (sCJD) patients and a cognitively normal control
      group of similar age distribution. We genotyped the same polymorphisms in two
      other sample groups of sCJD cases from Italy and the UK. In addition, we compared
      MAPT haplotypes between sCJD and variant CJD (vCJD) patients. RESULTS: Single
      locus and haplotype analyses did not detect any significant difference between
      sCJD cases and controls. When we compared MAPT haplotypes between sCJD and
      variant CJD (vCJD) patients, we found that two of them were represented
      differently (H1f: 8% in sCJD versus 2% in vCJD; H1j:1% in sCJD versus 7% in
      vCJD). However, these two haplotypes were rare in both groups of patients, and
      taking the small sample sizes into account, we cannot exclude that the
      differences are due to chance. None of the p-values remained statistically
      significant after applying a multiple testing correction. CONCLUSION: Our study
      shows no evidence for an association between MAPT gene variations and sCJD, and
      some weak evidence for an association to vCJD.

PMID- 18072965
TI  - Penalized likelihood for sparse contingency tables with an application to full
      length cDNA libraries.
AB  - BACKGROUND: The joint analysis of several categorical variables is a common task
      in many areas of biology, and is becoming central to systems biology
      investigations whose goal is to identify potentially complex interaction among
      variables belonging to a network. Interactions of arbitrary complexity are
      traditionally modeled in statistics by log-linear models. It is challenging to
      extend these to the high dimensional and potentially sparse data arising in
      computational biology. An important example, which provides the motivation for
      this article, is the analysis of so-called full-length cDNA libraries of
      alternatively spliced genes, where we investigate relationships among the
      presence of various exons in transcript species. RESULTS: We develop methods to
      perform model selection and parameter estimation in log-linear models for the
      analysis of sparse contingency tables, to study the interaction of two or more
      factors. Maximum Likelihood estimation of log-linear model coefficients might not
      be appropriate because of the presence of zeros in the table's cells, and new
      methods are required. We propose a computationally efficient l1-penalization
      approach extending the Lasso algorithm to this context, and compare it to other
      procedures in a simulation study. We then illustrate these algorithms on
      contingency tables arising from full-length cDNA libraries. CONCLUSION: We
      propose regularization methods that can be used successfully to detect complex
      interaction patterns among categorical variables in a broad range of biological
      problems involving categorical variables.

PMID- 18072966
TI  - Diacylglycerol oil for the metabolic syndrome.
AB  - Excess adiposity has been shown to play a crucial role in the development of the
      metabolic syndrome. The elevated fasting and postprandial triglyceride-rich
      lipoprotein levels is the central lipid abnormality observed in the metabolic
      syndrome. Recent studies have indicated that diacylglycerol (DAG) is effective
      for fasting and postprandial hyperlipidemia and preventing excess adiposity by
      increasing postprandial energy expenditure. We will here discuss the mechanisms
      of DAG-mediated improvements in hyperlipidemia and in postprandial energy
      expenditure, and effects of DAG oil on lipid/glucose metabolism and on body fat.
      Further, the therapeutic application of DAG for the metabolic syndrome will be
      considered.

PMID- 18072967
TI  - Synpolydactyly and HOXD13 polyalanine repeat: addition of 2 alanine residues is
      without clinical consequences.
AB  - BACKGROUND: Type II syndactyly or synpolydactyly (SPD) is clinically very
      heterogeneous, and genetically three distinct SPD conditions are known and have
      been designated as SPD1, SPD2 and SPD3, respectively. SPD1 type is associated
      with expansion mutations in HOXD13, resulting in an addition of > or = 7 alanine
      residues to the polyalanine repeat. It has been suggested that expansions < or =
      6 alanine residues go without medical attention, as no such expansion has ever
      been reported with the SPD1 phenotype. METHODS: We describe a large Pakistani and
      an Indian family with SPD. We perform detailed clinical and molecular analyses to
      identify the genetic basis of this malformation. RESULTS: We have identified four
      distinct clinical categories for the SPD1 phenotype observed in the affected
      subjects in both families. Next, we show that a milder foot phenotype, previously
      described as a separate entity, is in fact a part of the SPD1 phenotypic
      spectrum. Then, we demonstrate that the phenotype in both families segregates
      with an identical expansion mutation of 21 bp in HOXD13. Finally, we show that
      the HOXD13 polyalanine repeat is polymorphic, and the expansion of 2 alanine
      residues, evident in unaffected subjects of both families, is without clinical
      consequences. CONCLUSION: It is the first molecular evidence supporting the
      hypothesis that expansion of < or = 6 alanine residues in the HOXD13 polyalanine
      repeat is not associated with the SPD1 phenotype.

PMID- 18072969
TI  - Determining promoter location based on DNA structure first-principles
      calculations.
AB  - A new method for the prediction of promoter regions based on atomic molecular
      dynamics simulations of small oligonucleotides has been developed. The method
      works independently of gene structure conservation and orthology and of the
      presence of detectable sequence features. Results obtained with our method
      confirm the existence of a hidden physical code that modulates genome expression.

PMID- 18072968
TI  - Leptospirosis vaccines.
AB  - Leptospirosis is a serious infection disease caused by pathogenic strains of the
      Leptospira spirochetes, which affects not only humans but also animals. It has
      long been expected to find an effective vaccine to prevent leptospirosis through
      immunization of high risk humans or animals. Although some leptospirosis vaccines
      have been obtained, the vaccination is relatively unsuccessful in clinical
      application despite decades of research and millions of dollars spent. In this
      review, the recent advancements of recombinant outer membrane protein (OMP)
      vaccines, lipopolysaccharide (LPS) vaccines, inactivated vaccines, attenuated
      vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of
      these vaccines may lead to development of new potential methods to combat
      leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a
      vaccine ontology database was built for the scientists working on the
      leptospirosis vaccines as a starting tool.

PMID- 18072971
TI  - The impact of citrate introduction at UK syringe exchange programmes: a
      retrospective cohort study in Cheshire and Merseyside, UK.
AB  - BACKGROUND: In 2003, it became legal in the UK for syringe exchange programmes
      (SEPs) to provide citrate to injecting drug users to solubilise heroin. Little
      work has been undertaken on the effect of policy change on SEP function. Here, we
      examine whether the introduction of citrate in Cheshire and Merseyside SEPs has
      altered the number of heroin/crack injectors accessing SEPs, the frequency at
      which heroin/crack injectors visited SEPs and the number of syringes dispensed.
      METHODS: Eleven SEPs in Cheshire and Merseyside commenced citrate provision in
      2003. SEP-specific data for the six months before and six months after citrate
      was introduced were extracted from routine monitoring systems relating to heroin
      and crack injectors. Analyses compared all individuals attending pre and post
      citrate and matched analyses only those individuals attending in both periods
      (defined as 'longitudinal attenders'). Non-parametric tests were used throughout.
      RESULTS: Neither new (first seen in either six months period) nor established
      clients visited SEPs more frequently post citrate. New clients collected
      significantly less syringes per visit post citrate, than pre citrate (14.5,10.0;
      z = 1.992, P < 0.05). Matched pair analysis showed that the median number of
      visits for 'longitudinal attenders' (i.e. those who attended in both pre and post
      citrate periods) increased from four pre citrate to five post citrate (z = 2.187,
      P < 0.05) but the number of syringes collected remained unchanged. These changes
      were not due to seasonal variation or other changes in service configuration.
      CONCLUSION: The introduction of citrate did not negatively affect SEP attendance.
      'Longitudinal attenders' visited SEPs more frequently post citrate, providing
      staff with greater opportunity for intervention and referral. As the number of
      syringes they collected each visit remained unchanged the total number of clean
      syringes made available to this group of injectors increased very slightly
      between the pre and post citrate periods. However, new clients collected
      significantly less syringes post citrate than pre citrate, possibly due to staff
      concerns regarding the amount of citrate (and thus syringes) to dispense safely
      to new clients. These concerns should not be allowed to negatively impact on the
      number of syringes dispensed.

PMID- 18072970
TI  - Methionine aminopeptidase-2 blockade reduces chronic collagen-induced arthritis:
      potential role for angiogenesis inhibition.
AB  - The enzyme methionine aminopeptidase-2 (MetAP-2) is thought to play an important
      function in human endothelial cell proliferation, and as such provides a valuable
      target in both inflammation and cancer. Rheumatoid arthritis (RA) is a chronic
      inflammatory disease associated with increased synovial vascularity, and hence is
      a potential therapeutic target for angiogenesis inhibitors. We examined the use
      of PPI-2458, a selective non-reversible inhibitor of MetAP-2, in disease models
      of RA, namely acute and chronic collagen-induced arthritis (CIA) in mice. Whilst
      acute CIA is a monophasic disease, CIA induced with murine collagen type II
      manifests as a chronic relapsing arthritis and mimics more closely the disease
      course of RA. Our study showed PPI-2458 was able to reduce clinical signs of
      arthritis in both acute and chronic CIA models. This reduction in arthritis was
      paralleled by decreased joint inflammation and destruction. Detailed mechanism of
      action studies demonstrated that PPI-2458 inhibited human endothelial cell
      proliferation and angiogenesis in vitro, without affecting production of
      inflammatory cytokines. Furthermore, we also investigated release of inflammatory
      cytokines and chemokines from human RA synovial cell cultures, and observed no
      effect of PPI-2458 on spontaneous expression of cytokines and chemokines, or
      indeed on the angiogenic molecule vascular endothelial growth factor (VEGF).
      These results highlight MetAP-2 as a good candidate for therapeutic intervention
      in RA.

PMID- 18072972
TI  - Laparoscopic cholecystectomy for melanoma metastatic to the gallbladder: is it an
      adequate surgical procedure? Report of a case and review of the literature.
AB  - BACKGROUND: Only 2% to 4% of patients with melanoma will be diagnosed with
      gastrointestinal metastasis during the course of their disease. The most common
      sites of gastrointestinal metastases from melanoma include the small bowel (35%
      67%), colon (9%-15%) and stomach (5%-7%), with a median survival of 6-10 months
      after surgery, and 18% survival at five years. Metastatic melanoma to the
      gallbladder is extremely rare and it is associated with a very poor prognosis.
      CASE PRESENTATION: We report a case of a 54-year old man presented to observation
      with diagnosis of 6.1 mm thick, Clark's level IV, ulcerated melanoma of the
      trunk, developing in the course of the disease metastatic involvement of the
      gallbladder as first site of recurrence, treated by laparoscopic cholecystectomy.
      To date only few cases of patients with metastatic melanoma of the gallbladder
      treated by this surgical procedure have been reported in literature. CONCLUSION:
      Gallbladder metastasis represents a rare event as a first site of recurrence. It
      must be considered a possible expression of systemic disease also despite
      radiological absence of other metastatic lesions. Laparoscopic approach has a
      possible therapeutic role, but open surgery has also a concomitant diagnostic
      purpose because gives the possibility of manual exploration of abdominal cavity,
      useful particularly to reveal bowel metastatic lesions, not easily identifiable
      by preoperative imaging examinations.

PMID- 18072973
TI  - Efficient and accurate P-value computation for Position Weight Matrices.
AB  - BACKGROUND: Position Weight Matrices (PWMs) are probabilistic representations of
      signals in sequences. They are widely used to model approximate patterns in DNA
      or in protein sequences. The usage of PWMs needs as a prerequisite to knowing the
      statistical significance of a word according to its score. This is done by
      defining the P-value of a score, which is the probability that the background
      model can achieve a score larger than or equal to the observed value. This gives
      rise to the following problem: Given a P-value, find the corresponding score
      threshold. Existing methods rely on dynamic programming or probability generating
      functions. For many examples of PWMs, they fail to give accurate results in a
      reasonable amount of time. RESULTS: The contribution of this paper is two fold.
      First, we study the theoretical complexity of the problem, and we prove that it
      is NP-hard. Then, we describe a novel algorithm that solves the P-value problem
      efficiently. The main idea is to use a series of discretized score distributions
      that improves the final result step by step until some convergence criterion is
      met. Moreover, the algorithm is capable of calculating the exact P-value without
      any error, even for matrices with non-integer coefficient values. The same
      approach is also used to devise an accurate algorithm for the reverse problem:
      finding the P-value for a given score. Both methods are implemented in a software
      called TFM-PVALUE, that is freely available. CONCLUSION: We have tested TFM
      PVALUE on a large set of PWMs representing transcription factor binding sites.
      Experimental results show that it achieves better performance in terms of
      computational time and precision than existing tools.

PMID- 18072975
TI  - Comments on the nonpharmaceutical interventions in New York City and Chicago
      during the 1918 flu pandemic.
AB  - This commentary was originally published in CIDRAP News and it is here reported
      almost verbatim to allow divulgation through open access. The Editorial
      summarizes John Barry's concerns about the value of accurate historical reporting
      and its implications in public policy determination. This short abstract was
      written by the Editor-in-Chief of the Journal of Translational Medicine to
      introduce the Editorial.

PMID- 18072974
TI  - Promotion of couples' voluntary counselling and testing for HIV through
      influential networks in two African capital cities.
AB  - BACKGROUND: Most new HIV infections in Africa are acquired from cohabiting
      heterosexual partners. Couples' Voluntary Counselling and Testing (CVCT) is an
      effective prevention strategy for this group. We present our experience with a
      community-based program for the promotion of CVCT in Kigali, Rwanda and Lusaka,
      Zambia. METHODS: Influence Network Agents (INAs) from the health, religious, non
      governmental, and private sectors were trained to invite couples for CVCT.
      Predictors of successful promotion were identified using a multi-level
      hierarchical analysis. RESULTS: In 4 months, 9,900 invitations were distributed
      by 61 INAs, with 1,411 (14.3%) couples requesting CVCT. INAs in Rwanda
      distributed fewer invitations (2,680 vs. 7,220) and had higher response rates
      (26.9% vs. 9.6%), than INAs in Zambia. Context of the invitation event, including
      a discreet location such as the INA's home (OR 3.3-3.4), delivery of the
      invitation to both partners in the couple (OR 1.6-1.7) or to someone known to the
      INA (OR 1.7-1.8), and use of public endorsement (OR 1.7-1.8) were stronger
      predictors of success than INA or couple-level characteristics. CONCLUSION:
      Predictors of successful CVCT promotion included strategies that can be easily
      implemented in Africa. As new resources become available for Africans with HIV,
      CVCT should be broadly implemented as a point of entry for prevention, care and
      support.

PMID- 18072976
TI  - Information for decision making from imperfect national data: tracking major
      changes in health care use in Kenya using geostatistics.
AB  - BACKGROUND: Most Ministries of Health across Africa invest substantial resources
      in some form of health management information system (HMIS) to coordinate the
      routine acquisition and compilation of monthly treatment and attendance records
      from health facilities nationwide. Despite the expense of these systems, poor
      data coverage means they are rarely, if ever, used to generate reliable evidence
      for decision makers. One critical weakness across Africa is the current lack of
      capacity to effectively monitor patterns of service use through time so that the
      impacts of changes in policy or service delivery can be evaluated. Here, we
      present a new approach that, for the first time, allows national changes in
      health service use during a time of major health policy change to be tracked
      reliably using imperfect data from a national HMIS. METHODS: Monthly attendance
      records were obtained from the Kenyan HMIS for 1 271 government-run and 402 faith
      based outpatient facilities nationwide between 1996 and 2004. A space-time
      geostatistical model was used to compensate for the large proportion of missing
      records caused by non-reporting health facilities, allowing robust estimation of
      monthly and annual use of services by outpatients during this period. RESULTS: We
      were able to reconstruct robust time series of mean levels of outpatient
      utilisation of health facilities at the national level and for all six major
      provinces in Kenya. These plots revealed reliably for the first time a period of
      steady nationwide decline in the use of health facilities in Kenya between 1996
      and 2002, followed by a dramatic increase from 2003. This pattern was consistent
      across different causes of attendance and was observed independently in each
      province. CONCLUSION: The methodological approach presented can compensate for
      missing records in health information systems to provide robust estimates of
      national patterns of outpatient service use. This represents the first such use
      of HMIS data and contributes to the resurrection of these hugely expensive but
      underused systems as national monitoring tools. Applying this approach to Kenya
      has yielded output with immediate potential to enhance the capacity of decision
      makers in monitoring nationwide patterns of service use and assessing the impact
      of changes in health policy and service delivery.

PMID- 18072977
TI  - The urologic epithelial stem cell database (UESC) - a web tool for cell type
      specific gene expression and immunohistochemistry images of the prostate and
      bladder.
AB  - BACKGROUND: Public databases are crucial for analysis of high-dimensional gene
      and protein expression data. The Urologic Epithelial Stem Cells (UESC) database
      http://scgap.systemsbiology.net/ is a public database that contains gene and
      protein information for the major cell types of the prostate, prostate cancer
      cell lines, and a cancer cell type isolated from a primary tumor. Similarly, such
      information is available for urinary bladder cell types. DESCRIPTION: Two major
      data types were archived in the database, protein abundance localization data
      from immunohistochemistry images, and transcript abundance data principally from
      DNA microarray analysis. Data results were organized in modules that were made to
      operate independently but built upon a core functionality. Gene array data and
      immunostaining images for human and mouse prostate and bladder were made
      available for interrogation. Data analysis capabilities include: (1) CD (cluster
      designation) cell surface protein data. For each cluster designation molecule, a
      data summary allows easy retrieval of images (at multiple magnifications). (2)
      Microarray data. Single gene or batch search can be initiated with Affymetrix
      Probeset ID, Gene Name, or Accession Number together with options of coalescing
      probesets and/or replicates. CONCLUSION: Databases are invaluable for biomedical
      research, and their utility depends on data quality and user friendliness. UESC
      provides for database queries and tools to examine cell type-specific gene
      expression (normal vs. cancer), whereas most other databases contain only whole
      tissue expression datasets. The UESC database provides a valuable tool in the
      analysis of differential gene expression in prostate cancer genes in cancer
      progression.

PMID- 18072978
TI  - A long-term follow-up study investigating health-related quality of life and
      resource use in survivors of severe sepsis: comparison of recombinant human
      activated protein C with standard care.
AB  - INTRODUCTION: Recombinant human activated protein C (APC) therapy has been shown
      to reduce short-term mortality in patients with severe sepsis. However, survivors
      of sepsis may have long-term complications affecting health-related quality of
      life (HRQoL) and resource utilization. The objective of this study was to
      evaluate prospectively the effect of APC on long-term HRQoL and resource
      utilization compared with a nonrandomized control group that received standard
      care. METHODS: This was an observational cohort study at nine Canadian intensive
      care units. Patients with severe sepsis who survived to 28 days were recruited.
      Patients who received APC formed the treatment group and those that did not
      formed the standard care group. Patients who did not receive APC because of
      central nervous system bleeding risk were excluded from the standard care group.
      HRQoL (determined using the 36-item Short Form) and resource use were recorded at
      28 days, and 3, 5 and 7 months. RESULTS: One hundred patients were enrolled (64
      in the standard care group and 36 in the APC group), with 70 patients completing
      all follow-up visits. Over the 6 months of follow up, APC-treated patients
      exhibited statistically significantly better scores for the physical component
      score (P = 0.04) and trends toward improvements in physical functioning (P =
      0.12), role physical (P = 0.10) and bodily pain (P = 0.14) as compared with
      standard care patients. Shorter hospital length of stay was observed for the APC
      group (36 days versus 48 days; P = 0.05). CONCLUSION: These findings challenge
      earlier assumptions suggesting equivalent HRQoL and resource use in APC-treated
      and standard care patients who survive severe sepsis.

PMID- 18072979
TI  - The tert-amino effect in heterocyclic chemistry: synthesis of new fused
      pyrazolinoquinolizine and 1,4-oxazinopyrazoline derivatives.
AB  - The synthesis of novel fused heterocycles is based on reactions proceeding by the
      mechanism of the tert-amino effect, which generalizes cyclization of certain
      derivatives of 3-methyl-1-phenyl-2-pyrazolin-5-ones. Using this strategy a
      variety of fused heterocycles is obtained by the Knoevenagel condensation of 5
      tert-amino-3-methyl-1-phenylpyrazolone-4-carboxal-dehyde 3 with active methylene
      compounds such as malononitrile and cyanoacetamide followed by cyclisation using
      anhydrous zinc chloride.

PMID- 18072980
TI  - Housing, income support and mental health: points of disconnection.
AB  - There exists a disconnection between evolving policies in the policy arenas of
      mental health, housing, and income support in Canada. One of the complexities
      associated with analysing the intersection of these policies is that federal,
      provincial, and municipal level policies are involved. Canada is one of the few
      developed countries without a national mental health policy and because of the
      federal policy reforms of the 1970s, the provincial governments now oversee the
      process of deinstitutionalization from the hospital to the community level.
      During this same period the availability of affordable housing has decreased as
      responsibility for social housing has been transfered from the federal government
      to the provincial and/or municipal levels of government. Canada also stands alone
      in terms of being a developed nation without national housing policy instead what
      is considered "affordable" housing is partially dependant upon individuals'
      personal economic resources. As well, over the past decade rates of income
      supports have also been reduced. Psychiatric survivors have long been identified
      as being at risk for homelessness, with the disconnection existing between
      housing, income and mental health policies and the lack of a national policy in
      any of these policies areas further contributing to this risk.

PMID- 18072981
TI  - Current evidence for subjective cognitive impairment (SCI) as the pre-mild
      cognitive impairment (MCI) stage of subsequently manifest Alzheimer's disease.

PMID- 18072982
TI  - Clinical features of MCI: motor changes.
AB  - Mild cognitive impairment (MCI) is a classification reserved for nondemented
      elderly individuals at increased risk for future decline to dementia, compared to
      those with normal cognition. Cognitive tests, particularly those assessing verbal
      recall, have been found to be useful in the identification of elderly people with
      MCI. We argue that a variety of motor/psychomotor evaluations are also sensitive
      to MCI. Motor assessments described as complex correctly categorize normal versus
      MCI elderly with comparable accuracies to those obtained by cognitive tests.
      Unlike performance on verbally based cognitive measures, motor-test scores appear
      to be relatively independent of educational attainment, indicating that the use
      of certain motor tests may be particularly valuable in the identification of MCI
      among elderly with widely varying educational backgrounds.

PMID- 18072983
TI  - Hormonal treatment, mild cognitive impairment and Alzheimer's disease.
AB  - A plethora of in vitro and in vivo studies have supported the neuroprotective
      role of estrogens and their impact on the neurotransmitter systems implicated in
      cognition. Recent hormonal replacement therapy (HRT) trials in non-demented
      postmenopausal women suggest a temporary positive effect (notably on verbal
      memory), and four meta-analyses converge to suggest a possible protective effect
      in relation to Alzheimer's disease (reducing risk by 29 to 44%). However, data
      from the only large randomized controlled trial published to date, the Women's
      Health Initiative Memory Study, did not confirm these observations and have even
      suggested an increase in dementia risk for women using HRT compared to controls.
      Apart from methodological differences, one key shortcoming of this trial has
      probably been the focus on late-onset (postmenopausal) hormonal changes, i.e. at
      a time when the neurodegenerative process has already begun and without taking
      into account individual lifetime exposure to hormone variability. Multifactorial
      models based on an exhaustive view of all hormonal events throughout the
      reproductive life (rather than on a specific exposure to a given steroid)
      together with other risk factors (notably genetic risk factors related to
      estrogen receptor polymorphisms) should be explored to clarify the role of
      hormonal risk factors, or protective factors for cognitive dysfunction and
      dementia.

PMID- 18072984
TI  - Quantitative studies of ribosome conformational dynamics.
AB  - The ribosome is a dynamic machine that undergoes many conformational
      rearrangements during the initiation of protein synthesis. Significant
      differences exist between the process of protein synthesis initiation in
      eubacteria and eukaryotes. In particular, the initiation of eukaryotic protein
      synthesis requires roughly an order of magnitude more initiation factors to
      promote efficient mRNA recruitment and ribosomal recognition of the start codon
      than are needed for eubacterial initiation. The mechanisms by which these
      initiation factors promote ribosome conformational changes during stages of
      initiation have been studied using cross-linking, footprinting, site-directed
      probing, cryo-electron microscopy, X-ray crystallography, fluorescence
      spectroscopy and single-molecule techniques. Here, we review how the results of
      these different approaches have begun to converge to yield a detailed molecular
      understanding of the dynamic motions that the eukaryotic ribosome cycles through
      during the initiation of protein synthesis.

PMID- 18072985
TI  - Sertraline-induced hyponatremia in the elderly.

PMID- 18072987
TI  - Efficacy, safety and patient satisfaction of propofol for procedural sedation and
      analgesia in the emergency department: a prospective study.
AB  - OBJECTIVE: We evaluated the efficacy, safety and patient satisfaction with the
      use of propofol for procedural sedation and analgesia in the emergency department
      (ED). METHODS: All patients receiving propofol for procedural sedation and
      analgesia in the ED between December 1, 2003, and November 30, 2005, were
      prospectively assessed. Propofol was administered using a standardized protocol,
      which included an initial dose of 0.25-0.5 mg/kg followed by 10-20 mg/minute
      until sedated. Efficacy was evaluated using procedural success rate, recovery
      time and physician satisfaction. Adverse respiratory effects were defined as
      apnea for more than 30 seconds or an oxygen saturation of less than 90%.
      Hypotension was defined as systolic blood pressure < 90 mm Hg or > 20% decrease
      from baseline. Patient and physician satisfaction were determined using 5-point
      Likert scales. RESULTS: Our study included 113 patients with a mean age of 50
      (standard deviation [SD] 19) years; 62% were male. The most common procedures
      were orthopedic manipulation (44%), cardioversion (37%), and abscess incision and
      drainage (13%). The mean total propofol dose required was 1.6 (SD 0.9) mg/kg.
      Procedural success was achieved in 90% of cases and the mean patient recovery
      time was 7.6 (SD 3.4) minutes. No patient (0%, 95% confidence interval [CI] 0%
      3%) experienced apnea; however, 1 patient (1%, 95% CI 0%-5%) experienced emesis,
      which resulted in an oxygen saturation < 90%. Nine patients (8%, 95% CI 4%-15%)
      experienced hypotension and 7 (6%, 95% CI 3%-12%) experienced pain on injection.
      All patients were very satisfied (92%, 95% CI 85%-96%) or satisfied (8%, 95% CI
      4%-15%), and 94% (95% CI 88%-98%) reported no recollection of the procedure. The
      majority of physicians were very satisfied (85%, 95% CI 77%-91%) or satisfied
      (6%, 95% CI 3%-12%) with the sedation and the conditions achieved. CONCLUSION:
      When administered as part of a standardized protocol, propofol appears to be a
      safe and effective agent for performing procedural sedation and analgesia in the
      ED, and is associated with high patient and physician satisfaction.

PMID- 18072988
TI  - Patients presenting to the emergency department: the use of other health care
      services and reasons for presentation.
AB  - OBJECTIVE: Some low-acuity emergency department (ED) presentations are considered
      convenience visits and potentially avoidable with improved access to primary care
      services. This study assessed the frequency and determinants of patients' efforts
      to access alternative care before ED presentation. METHODS: Patients aged 17
      years and older were randomly selected from 2 urban ED sites in Edmonton. Survey
      data were collected on use and characteristics of alternative care before the ED
      visit. Information was also collected on patient demographics and factors
      influencing their perception of whether the ED was the best care option. RESULTS:
      Of the 1,389 patients approached, 905 (65%) completed the survey and data from
      894 participants were analyzed. Sixty-one percent reported that they sought
      alternative care before visiting the ED. Eighty-nine of the patients who
      attempted alternative access before the ED visit felt that the ED was their best
      care option. Results of the multivariate logistic regression analysis showed that
      injury presentation, living arrangements, smoking status and whether or not
      patients had a family practitioner were predictors for seeking alternative care
      before visiting the ED. CONCLUSION: Most ambulatory patients attempt to look for
      other sources of care before presenting to the ED. Despite this attempted access
      to alternative care, while patients wait for ED care, they perceive that the ED
      is their best care option at that point in time.

PMID- 18072989
TI  - Emergency department patient compliance with follow-up for outpatient exercise
      stress testing: a randomized controlled trial.
AB  - INTRODUCTION: Numerous patients are assessed in the emergency department (ED) for
      chest pain suggestive of acute coronary syndrome (ACS) and subsequently
      discharged if found to be at low risk. Exercise stress testing is frequently
      advised as a follow-up investigation for low-risk patients; however, compliance
      with such recommendations is poorly understood. We sought to determine if
      compliance with follow-up for exercise stress testing is higher in patients for
      whom the investigation is ordered at the time of ED discharge, compared with
      patients who are advised to arrange testing through their family physician (FP).
      METHODS: Low-risk chest pain patients being discharged from the ED for outpatient
      exercise stress test and FP follow-up were randomized into 2 groups. ED staff
      ordered an exercise stress test for the intervention group, and the control group
      was advised to contact their FP to arrange testing. The primary outcome was
      completion of an exercise stress test at 30 days, confirmed through both patient
      contact and stress test results. Patients were unaware that our primary interest
      was their compliance with the exercise stress testing recommendations. RESULTS:
      Two-hundred and thirty-one patients were enrolled and baseline characteristics
      were similar between the 2 groups. Completion of an exercise stress test at 30
      days occurred in 87 out of 120 (72.5%) patients in the intervention group and 60
      out of 107 (56.1%) patients in the control group. The difference in compliance
      rates (16.4%) between the 2 groups was statistically significant (Chi(2) = 6.69,
      p < 0.001) with a relative risk of 1.29 (95% confidence interval 1.18-1.40), and
      the results remained significant after a "worst case" sensitivity analysis
      involving 4 control group cases lost to follow-up. When subjects were contacted
      by telephone 30 days after the ED visit, 60% of those who were noncompliant
      patients felt they did not have a heart problem and that further testing was
      unnecessary. CONCLUSION: When ED staff order an outpatient exercise stress test
      following investigation for potential ACS, patients are more likely to complete
      the test if it is booked for them before ED discharge. After discharge, many low
      risk chest pain patients feel they are not at risk and do not return to their FP
      for further testing in a timely manner as advised. Changing to a strategy of ED
      booking of exercise stress testing may help earlier identification of patients
      with coronary heart disease.

PMID- 18072990
TI  - Factors associated with delay to emergency department presentation, antibiotic
      usage and admission for human bite injuries.
AB  - OBJECTIVES: Evidence and consensus on best practices on the management of human
      bite injuries is lacking. Our objective was to identify factors that are
      associated with delay to emergency department (ED) presentation, antibiotic usage
      and patient admission. METHODS: We present a retrospective chart review of adults
      treated for human bites. Multivariable logistic regression models used
      demographic characteristics and bite circumstances and characteristics as factors
      associated with ED presentation more than 24 hours after the bite, antibiotic
      usage and hospital admission. RESULTS: Of the 388 patients evaluated for a human
      bite, 66.5% were bitten during an altercation; 23.8% presented more than 24 hours
      after the bite; 50.3% were bitten on the hands or fingers, 23.5% on an extremity
      and 17.8% on the head or neck. Only 7.7% of all patients sustained closed-fist
      injuries; the majority had occlusional or other kinds of bites. The majority of
      patients (77.3%) received antibiotics and 11.1% were admitted to hospital.
      Patients who had greater odds of presenting more than 24 hours after the bite
      were black (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.02-3.13),
      Hispanic (OR 2.68, 95% CI 1.22-5.89) and those who had a non-occupational bite
      (OR 3.87, 95% CI, 1.68-8.90). Patients had a greater chance of receiving
      antibiotics if they were bitten during an altercation (OR 1.87, 95% CI, 1.09
      3.20) and were bitten on the hands or fingers (OR 2.23, 95% CI 1.31-3.80).
      Patients had a greater chance of being admitted to the hospital if they were
      bitten during an altercation (OR 4.91, 95% CI 1.65-14.64), bitten on the hands or
      fingers (OR 5.26, 95% CI, 1.74-15.87) and if they presented >or= 24 hours after
      the bite. CONCLUSION: Most patients presented to the ED within 24 hours of their
      injury and received antibiotics. The circumstances surrounding the bite appeared
      to be associated with delay to ED presentation, receipt of antibiotics and
      admission to the hospital. There are ethnic background differences in delay to ED
      presentation. ED clinicians in our study favour antibiotic usage and admission
      based on the body location of the bite, despite little evidence to support these
      practices.

PMID- 18072991
TI  - Emergency medicine training demographics of physicians working in rural and
      regional southwestern Ontario emergency departments.
AB  - OBJECTIVES: We sought to determine the emergency medicine training demographics
      of physicians working in rural and regional emergency departments (EDs) in
      southwestern Ontario. METHODS: A confidential 8-item survey was mailed to ED
      chiefs in 32 community EDs in southwestern Ontario during the month of March
      2005. This study was limited to nonacademic centres. RESULTS: Responses were
      received from 25 (78.1%) of the surveyed EDs, and demographic information on 256
      physicians working in those EDs was obtained. Of this total, 181 (70.1%)
      physicians had no formal emergency medicine (EM) training. Most were members of
      the College of Family Physicians of Canada (CCFPs). The minimum qualification to
      work in the surveyed EDs was a CCFP in 8 EDs (32.0%) and a CCFP with Advanced
      Cardiac and Trauma Resuscitation Courses (ACLS and ATLS) in 17 EDs (68.0%). None
      of the surveyed EDs required a CCFP(EM) or FRCP(EM) certification, even in
      population centres larger than 50 000. CONCLUSION: The majority of physicians
      working in southwestern Ontario community EDs graduated from family medicine
      residencies, and most have no formal EM training or certification. This
      information is of relevance to both family medicine and emergency medicine
      residency training programs. It should be considered in the determination of
      curriculum content and the appropriate number of residency positions.

PMID- 18072992
TI  - Pediatric emergency medicine: a world of potential.

PMID- 18072993
TI  - Do fluoroquinolones commonly cause arthropathy in children?
AB  - OBJECTIVE: The objective of this paper was to review the relation between
      fluoroquinolone (FQ) use and arthropathy in children. METHODS: The biomedical
      literature from January 1980 to February 2007 was searched using PubMed. Key
      search terms included fluoroquinolones, arthropathy, tendinopathy and children.
      Literature was included if it was a clinical trial or meta-analysis examining the
      use of 1 or more FQs in a pediatric human population and if it had a primary
      outcome measure of reported incidence of arthropathy or tendinopathy. Articles
      were excluded if the primary outcome measure was efficacy of an FQ in a
      particular pediatric disease state, and evaluated safety was a secondary end
      point. RESULTS: Data was reviewed from 4 large retrospective studies. Three of
      the 4 studies failed to find a significant link between musculoskeletal injury
      and FQ treatment. One study reported a correlation between use of pefloxacin and
      arthropathy, but the authors' conclusions supported the use of FQs in select
      pediatric cases. CONCLUSION: Arthropathy that occurs as a result of FQ use in
      children has not been adequately supported by published data from safety trials
      in human children. Concerns about arthropathy with FQs should not preclude their
      use by emergency physicians when appropriate and necessary in pediatric patients.

PMID- 18072994
TI  - Myth: nephrolithiasis and medical expulsive therapy.
AB  - There is a medical myth that ureteral stones larger than 5 mm will not pass
      spontaneously and require urological intervention for removal. Recent findings
      indicate that medical expulsive therapy can facilitate spontaneous passage for
      stones up to 10 mm. For the management of ureteral stones, we recommend
      administering tamsulosin and a corticosteroid (deflazacort or prednisone) along
      with the standard therapy of analgesics, antibiotics and hydration.

PMID- 18072995
TI  - Teenagers with Jimson weed (Datura stramonium) poisoning.
AB  - We report 2 cases of teenagers who were poisoned with Jimson weed (Datura
      stramonium) and presented to the emergency department with a severe acute
      anticholinergic toxidrome after ingestion of several hundred seeds. The patients
      presented with visual hallucinations, disorientation, incomprehensible and
      nonsensical speech, and dilated sluggish pupils. Both patients required
      restraints for combativeness until adequate sedation with lorazepam and
      haloperidol was achieved. Jimson weed is found in southern Canada and the United
      States and can cause acute anticholinergic poisoning and death in humans and
      animals. The treatment of choice for anticholinergic poisoning is mainly
      supportive care and gastrointestinal decontamination with activated charcoal.
      Jimson weed intoxication should be considered in cases of patients presenting
      with unexplained peripheral and central anticholinergic symptoms including
      delirium, agitation and seizures, especially among younger patients and
      partygoers. It is important that health care professionals recognize that Jimson
      weed is a toxic, indigenous, "wild" growing plant, subject to misuse and
      potentially serious intoxication requiring hospitalization.

PMID- 18072996
TI  - Airbag pneumonitis: a report and discussion of a new clinical entity.
AB  - This report describes the occurrence of pneumonitis in a young male immediately
      after inhalation of aerosolized chemicals subsequent to motor vehicle airbag
      deployment. The clinical presentation was one of mild shortness of breath
      associated with bilateral alveolar infiltrates on chest radiology. Not previously
      described, this diagnosis should be considered in the differential of pulmonary
      infiltrates in motor vehicle crash patients.

PMID- 18073000
TI  - Development of a nutrition counselling care map for dyslipidemia.
AB  - PURPOSE: Care maps or clinical pathways for nutrition therapy of dyslipidemia
      could add to current practice guidelines, by providing templates for feasible and
      recommended diet counselling processes. A care map was therefore developed by
      engaging expert and generalist dietitians and external experts from across Canada
      in a multi-stage consensus process. METHODS: First, a qualitative study was
      undertaken with a convenience sample of 12 practitioners to identify possible
      diet care options, using hypothetical client scenarios and cognitive analysis.
      Second, these care options were rated for five case scenarios considered typical
      (overweight clients, with or without clinical cardiovascular disease and other
      comorbidities, potentially motivated to change, consuming high-fat diets, and
      facing various major barriers to eating behaviour change). The rating was
      conducted through a survey of participants. Highly appropriate, recommended, and
      feasible options for counselling were ranked through a two-round modified Delphi
      process, with teleconference discussions between rounds. RESULTS: Forty-nine
      professionals started the consensus process; 39 (80%) completed all aspects.
      Numerous care processes were appropriate for all clients, with additional focus
      on barriers for low-income clients, sodium intake for clients with hypertension,
      and smoking cessation in smokers. CONCLUSIONS: The resulting care map,
      "Dietitians' Quick Reference Guide for Clinical Nutrition Therapy for Overweight
      Clients with Dyslipidemia," provides a basis for current practice and new
      effectiveness studies.

PMID- 18073001
TI  - Barriers to breastfeeding in a Vietnamese community: a qualitative exploration.
AB  - PURPOSE: Vietnamese women's breastfeeding experience and challenges were
      explored, as were their families' needs for prenatal and postpartum health
      professional programs and services. METHODS: A qualitative study was conducted in
      Middlesex-London, Ontario, using in-depth, semi-structured interviews in a
      heterogeneous sample of 11 Vietnamese mothers of children younger than two years.
      Diverse subject characteristics were sought in terms of parity, maternal age,
      infant age, marital status, education, employment, and breastfeeding initiation
      and duration. The 45- to 60-minute interviews were audiotaped and transcribed
      verbatim. Research team members independently reviewed interview transcripts at
      several stages during data collection. Qualitative analysis was sequential, and
      involved a combination of editing and template organizing styles. RESULTS: Lack
      of knowledge and misinformation were major barriers to breastfeeding. Inability
      to communicate in English and a lack of effective transportation were key
      obstacles to the women's ability to access mainstream prenatal and postpartum
      health programs and services. Standard nursing prenatal and postpartum services
      appear not to have reached this group of mothers effectively. CONCLUSIONS:
      Culturally and linguistically sensitive breastfeeding promotion and postpartum
      support services are needed for this Vietnamese community.

PMID- 18073002
TI  - Nutrition and physical activity interventions for low-income populations.
AB  - A systematic review was conducted of community-based nutrition and physical
      activity strategies for chronic disease prevention targeting low-income
      populations. A computer search of the relevant published literature from 1996 to
      2004 was done using Medline, EMBASE, ERIC, CINAHL, PubMed, and HealthSTAR
      databases. The primary objective was to develop an inventory of intervention
      strategies. The interventions ranged in approach from traditional group sessions
      taught by allied health professionals, peer-led workshops, one-on-one counselling
      print material, and home-based telephone and mail interventions to multimedia
      strategies and experiential activities such as food demonstrations and group
      exercise. The results suggest that nutrition and physical activity interventions
      aimed at low-income audiences tend to be delivered in an interactive visual
      format, to be culturally appropriate, to be administered in accessible primary
      care settings, and to provide incentives.

PMID- 18073003
TI  - Dietetic prior learning assessment: student and faculty experiences.
AB  - Prior learning assessment (PLA) is a process for documenting competence gained
      through formal and informal opportunities. It has been endorsed by adult
      educators but is not widely used in dietetic education. Graduate students at a
      Canadian university, who have prior learning relevant to dietetics, are given the
      opportunity to develop a portfolio documenting competence in lieu of portions of
      formal internship experience. An exploratory descriptive methodology is used to
      describe the experiences of graduate students (n=6) and faculty (n=3) who
      participated in this innovative program from 2000 to 2005. All students
      successfully completed portfolios for one-third or more of their internship.
      After completing the documentation process, students participated in semi
      structured interviews consisting of 16 open-ended questions. Faculty completed a
      five-item survey designed to capture their experiences with the PLA process.
      Student and faculty data were thematically analyzed and several risks and
      benefits were documented. Results indicate that, overall, both students and
      faculty viewed the PLA as a positive experience. Because of the limited
      placements available for practical internship experiences, PLA can be a useful
      process for the confirmation of dietetic competence.

PMID- 18073004
TI  - Food preferences and meal satisfaction of meals on wheels recipients.
AB  - PURPOSE: To investigate Edmonton Meals on Wheels (MOW) recipients' food
      preferences and meal satisfaction. METHODS: A preliminary study of 13 lunch club
      participants divided into two focus groups was conducted to determine overall
      themes in clients' menu preferences and suggestions. A questionnaire was
      developed, based on previous MOW client comments, and delivered to all clients
      (n=271) receiving hot meal service from the Edmonton MOW program; 140 surveys
      (52% response rate) were returned. RESULTS: The majority (72% to 88%) of hot meal
      clients were satisfied with the taste, texture, value, variety, and portion size
      of their meals. Popular menu items were barbecued chicken, perogies, and
      desserts. Up to 25% of participants indicated that meats were too tough and
      vegetables were too firm. Vegetables such as broccoli and Brussels sprouts were
      the most commonly disliked items. CONCLUSIONS: Overall, clients find the Edmonton
      MOW menu foods appealing and enjoyable. MOW programs should advertise the
      availability of texture-modified foods and offer a variety of vegetables. Meal
      services for the elderly must continue to monitor meal acceptance as client needs
      change with our aging population.

PMID- 18073005
TI  - Folate intake of older adults before and after fortification of grain products.
AB  - PURPOSE: To determine whether fortification allowed older adults in the Kingston,
      Frontenac, and Lennox & Addington (KFL&A) Public Health area to obtain adequate
      amounts of food folate, and the proportion at risk of consuming more than the
      upper limit (UL) of folic acid (1,000 mcg). METHODS: Dietary intake of a
      convenience sample of 103 healthy, active older adults (age range: 65 to 95
      years) was measured using three 24-hour recalls. Dietary folate pre- and post
      fortification was estimated. RESULTS: Mean dietary folate increased from pre- to
      post-fortification, but 43.4% of women and 20% of men still consumed less than
      the Estimated Average Requirement of 320 mcg dietary folate equivalent. No
      intakes exceeded the UL. Participants whose diet met grain products and vegetable
      and fruit recommendations of Canada's Food Guide to Healthy Eating consumed
      significantly more folate. CONCLUSIONS: Despite fortification, some older adults
      in the KFL&A area may not be obtaining enough folate to meet their nutritional
      needs, and may be at risk for health problems associated with folate deficiency.
      However, without concomitant serum folate measurements, the proportion is not
      known. Dietitians need to continue promoting foods naturally rich in folate,
      along with folic acid-fortified foods. While none of the older adults consumed
      more than the UL, some could exceed this amount if folic acid supplements were
      added to a folic acid-rich diet.

PMID- 18073006
TI  - Iron deficiency anemia following prenatal nutrition interventions.
AB  - PURPOSE: Iron deficiency anemia (IDA) during pregnancy and infancy is still
      common in developed countries, especially in low-income groups. We examined the
      prevalence of anemia and IDA in healthy low-income pregnant women participating
      in the Early Childhood Initiatives (ECI) program, and in their infants when they
      reached six months of age. METHODS: Pregnant women were recruited by
      nutritionists. In mothers, hemoglobin (Hb), mean corpuscular volume, and serum
      ferritin (SF) were measured at 36 +/- 2 weeks of gestation. In infants, Hb, mean
      corpuscular volume, SF, serum iron, total iron binding capacity (TIBC), and
      transferrin saturation (TS) were measured at six months of age. Thirty-one mother
      infant pairs participated. RESULTS: Among the 31 pregnant women participating in
      the ECI program, six (19.4%) were anemic (Hb <110 g/L) and five (16.1%) suffered
      from IDA (Hb <110 g/L and SF <10 microg/L). Among infants, seven of 23 (30.4%)
      were anemic (Hb <110 g/L) and five of 23 (21.7%) suffered from IDA (Hb <110 g/L
      plus two of the following: TIBC >60 micromol/L, SF <10 microg/L, serum iron <5.3
      micromol/L, TS < or = 15%). CONCLUSIONS: The prevalence of anemia in this group
      of low-income pregnant women is comparable to that in privileged women. The
      prevalence of IDA in infants is comparable to that observed in other high-risk
      groups. Effective strategies are needed to prevent IDA in vulnerable groups.

PMID- 18073007
TI  - The effect of senofilcon A contact lenses compared to habitual contact lenses on
      ocular discomfort during exposure to a controlled adverse environment.
AB  - OBJECTIVE: Contact lens wear is often associated with signs and symptoms of
      ocular dryness. These drying effects can be exacerbated by certain environmental
      factors such as low humidity, wind, and visual tasks. The objective of the study
      was to compare the ability of senofilcon A contact lenses to subjects' habitual
      contact lenses to provide relief from the subjects' perceived ocular discomfort
      during contact lens wear in adverse environmental conditions. RESEARCH DESIGN AND
      METHODS: Eleven subjects completed a single-center, double-masked, randomized,
      cross-over, pilot clinical trial. At the qualification visit, and subsequently
      wearing senofilcon A study lenses (ACUVUE OASYS Brand Contact Lenses with
      HYDRACLEAR Plus) and control (habitual) lenses at the following visits, subjects
      underwent a total of three 75-min Controlled Adverse Environment (CAE) exposures.
      The primary efficacy variable measured during the 2-week, 3-visit trial was
      subject-reported ocular discomfort during CAE exposure measured on a five-point
      scale from 0 (none) to 4 (worst). The endpoint of ocular discomfort was evaluated
      using a two-sided t-test based on a longitudinal linear mixed model. Lenses were
      also evaluated for safety, and all adverse events were monitored. RESULTS:
      Subjects reported a significantly better mean comfort score when wearing
      senofilcon A contact lenses (1.62 +/- 0.71 units) compared to the mean comfort
      score reported when wearing habitual lenses (2.21 +/- 0.80 units) over the course
      of an entire CAE exposure (p = 0.0068). During exposure, senofilcon A lenses also
      yielded significantly better mean overall discomfort scores versus no lenses
      (2.73 +/- 0.79 points, p < 0.0001). CONCLUSIONS: Senofilcon A contact lenses
      provided greater relief of subjective ocular discomfort associated with lens wear
      in adverse environmental conditions than that afforded by both the habitual
      lenses of contact lens wearers as well as with no contact lens wear. These
      results should be verified in a larger, appropriately-powered study.

PMID- 18073008
TI  - Safety of prolonged sacral neuromodulation tined lead testing.
AB  - OBJECTIVE: Prolonged sacral neuromodulation (SNM) testing is more reliable for
      accurate patient selection than the usual test period of 4-7 days. However,
      prolonged testing was suspected to result in a higher complication rate due to
      infection via the percutaneous passage of the extension wire. Therefore, we
      prospectively assessed the complications associated with prolonged tined lead
      testing. PATIENTS AND METHODS: A consecutive series of 44 patients who underwent
      prolonged tined lead testing for at least 14 days between May 2002 and April 2007
      were evaluated. Complications during prolonged tined lead testing, during and
      after tined lead explantation and during follow-up after implantation of the
      implantable pulse generator (IPG) were registered prospectively. RESULTS: Four
      patients suffered from urgency-frequency syndrome, 13 from urge incontinence, 18
      from non-obstructive chronic urinary retention and nine from chronic pelvic pain
      syndrome. The median test phase was 30 days (interquartile range [IQR] 21-36).
      Thirty-two of the 44 patients (73%) had successful prolonged tined lead testing
      and 31 of these (97%) underwent the implantation of the IPG. The median follow-up
      of the IPG implanted patients was 31 months (IQR 20-41). The complication rate
      was 5% (2/44) during prolonged tined lead testing and 16% (5/31) during follow-up
      of the IPG implanted patients, respectively. None of the complications could be
      attributed to prolonged testing. No infections were observed during the study
      period. CONCLUSIONS: This prospective, observational non-randomised study
      suggests prolonged SNM tined lead testing is a safe procedure. Based on the low
      complication rate and the increased reliability for accurate patient selection,
      this method is proposed as a possible standard test procedure, subject to
      confirmation by further randomised, controlled clinical studies.

PMID- 18073009
TI  - Genital ulcerative disease and sexually transmitted urethritis and circumcision:
      a meta-analysis.
AB  - The objective of the study was to determine the relationship of circumcision
      status to the risk for genital ulcerative disease (GUD) and sexually transmitted
      urethritis. A MEDLINE search and a review of references in published articles
      identified studies addressing the risk of sexually transmitted urethritis or GUD
      based on circumcision status. Meta-analyses, sensitivity analysis, and
      exploration for publication bias were performed. Thirty articles fulfilled the
      inclusion criteria. The data from one study were published twice. GUD showed a
      trend towards being more common in genitally intact men (random-effects summary
      odds ratio [OR] = 1.34, 95% confidence interval [CI] = 0.98-1.82). When comparing
      men with GUD to men with 'genital discharge syndrome' (GDS), genitally intact men
      were more likely to have GUD (OR = 2.31, 95% CI = 1.70-3.15). There was no
      difference in the risk for chancroid based on circumcision status (OR = 0.91, 95%
      CI = 0.40-2.05), gonorrhoea (OR = 1.03, 95% CI = 0.82-1.29), or Chlamydia
      trachomatis infections (OR = 0.62, 95% CI = 0.32-1.19). Genitally intact men were
      less likely to be diagnosed with 'GDS' (OR = 0.83, 95% CI = 0.67-1.01) or non
      specific urethritis (OR = 0.80, 95% CI = 0.64-1.01). Adjustment for publication
      bias in the literature that applies to chlamydial infections gave a summary OR of
      0.46 (95% CI = 0.22-0.97). Significant between-study heterogeneity was a
      consistent finding. In conclusion, genitally intact men may be at greater risk
      for GUD, whereas circumcised men may be at greater risk for acquiring sexually
      transmitted urethritis in general, but there is no statistically significant
      difference in risk of gonococcal infection. Significant between-study
      heterogeneity and evidence of publication bias exclude the possibility of
      reaching a definitive conclusion regarding the association of circumcision status
      and these sexually transmitted infections.

PMID- 18073010
TI  - Binge drinking, sexual behaviour and sexually transmitted infection in the UK.
AB  - Associations between sexual risk and alcohol consumption may be self-evident but
      have eluded detailed examination in the UK. A cohort of 520 genitourinary (GU)
      medicine clinic attenders in the south of England were given a detailed
      questionnaire and compared with a matched cohort from the General Household
      Survey (GHS). Clinic attenders binged heavily--a median of 13 units on a usual
      night and 26 on a 'heavy' night, compared with six units in the GHS cohort. In
      all, 86% of clinic attenders exceeded the UK government 'binge drinking' level of
      six units, and 32% of subjects thought that alcohol played a role in their clinic
      attendance. A total of 77% had been drinking before sex with a new partner; of
      these, 65% were usually or occasionally very drunk. Binge drinking was increased
      in the 29% diagnosed with a bacterial sexually transmitted infection (P < 0.003).
      Of the women, 19% reported an unwanted pregnancy, with 28% drinking beforehand.

PMID- 18073011
TI  - The outcome of treatment of early latent syphilis and syphilis with undetermined
      duration in HIV-infected and HIV-uninfected patients.
AB  - The aim of the study was to compare the outcome of syphilis treatment in HIV
      infected and -uninfected patients. An observational study on patients diagnosed
      with early syphilis in three genitourinary clinics in the UK between January 2003
      and June 2005 was conducted. Failure of the initial Venereal Disease Research
      Laboratory (test) (VDRL) titre to decrease four-fold within 12 months in the
      absence of history of re-infection was considered as treatment failure. During
      the study period, 190 HIV-uninfected and 129 HIV-infected patients were
      diagnosed, and 161 (84%) HIV-uninfected and 100 (77.5%) HIV-positive patients
      with diagnosis of syphilis who had 24 months follow-up syphilis serology results
      were included in the study (P = 0.10). There were 381 and 508 follow-up episodes
      for HIV-infected and -uninfected patients, respectively, within 24 months. One
      HIV-infected patient was diagnosed with neuro-syphilis. After 12 months, 102
      (63%) HIV-uninfected and 76 (70%) HIV-infected patients were treated (P = 0.04).
      On Cox proportional hazard model, successful treatment after 12 months was
      associated with having VDRL titre more than 1:6 (hazard ratio [HR] 1.011; 95%
      confidence interval [CI], 1.004-1.019; P = 0.002). Those with negative
      immunoglobulin M enzyme immunoassay were less likely to have been successfully
      treated after 12 months (HR 0.676 [95% CI 0.518-0.883]; P = 0.004). HIV sero
      status, age, sex group and treatment regimen were not associated with success of
      treatment. In conclusion, HIV sero-status did not play a role in the outcome of
      syphilis treatment. Treatment failure in a proportion of HIV-infected patients is
      due to a slower decline in VDRL titre rather than lack of response to treatment.

PMID- 18073012
TI  - Factors affecting time to treatment following diagnosis of genital Chlamydia
      trachomatis infection in Scottish genitourinary medicine clinics.
AB  - Early treatment of genital Chlamydia trachomatis can reduce complications and
      transmission. Guidelines have proposed standards for how soon people should be
      treated following a test. Data from an audit of Scottish genitourinary (GU)
      medicine clinics was analysed to identify factors associated with a short
      interval to treatment of chlamydia. A sample of 538 cases of chlamydia diagnosed
      at 12 Scottish GU medicine clinics between 1 April 2005 and 30 June 2005 was
      studied. Variables assessed included: age, sex, sexuality, whether a contact,
      symptoms, whether microscopy was performed, time to lab result and how the result
      was given. Earlier treatment was associated with: being a contact, having
      symptoms, being male, performing microscopy (male patients only) and giving the
      result at a follow-up appointment. Most of these variables (sex, symptoms, etc.)
      are without the influence of clinic policies and the ones which can be influenced
      (microscopy and follow-up appointments) are becoming less common. Time to
      treatment of genital chlamydia might therefore increase in the future.

PMID- 18073013
TI  - Commandos do not use condoms.
AB  - The aim of this study was to determine private soldiers' knowledge and attitudes
      about the use of condoms. This study includes privates discharged from the
      Zincidere 1st Commando Brigade, Kayseri, Turkiye. This study was composed of
      volunteers (n = 481) who were present at their Brigade at the time of the
      research. Data were collected with a questionnaire. It was found that 44.7% of
      the privates had not used a condom. Reasons for not using a condom included the
      following: lack of enjoyment and feeling of discomfort, belief in its
      unreliability and the difficulty of obtaining one. Privates stated that they had
      knowledge regarding protection against sexually transmitted diseases (95.8%), the
      importance of always using condoms (84.8%) and the importance of having a single
      partner (60.7%). The results of this study show that although knowledge of
      condoms is relatively good, they are not widely used.

PMID- 18073014
TI  - Notification of syphilis test results by telephone: acceptability ratings in a
      community-based sample of Scottish gay men.
AB  - Notifying patients of the results of syphilis testing by telephone can be cost
      effective for clinic staff. This study compared the acceptability ratings among
      potential patients of three methods of learning of syphilis test results: with a
      call to a mobile phone; with a call to a home phone; and with the patient phoning
      in for results. A questionnaire was distributed to male clients of gay venues in
      Glasgow, Scotland, during 2005 (n = 150). Phoning in for results was rated as
      significantly more acceptable than either learning of results with a call to a
      mobile phone, or receiving a phone call at home (both P < 0.001). Further,
      receiving a call on a mobile phone was rated as significantly more acceptable
      than receiving a call at home (P < 0.001). It is recommended that patients be
      given the option of initiating the communication of test results.

PMID- 18073015
TI  - Patient-delivered partner medication in the UK: an unlawful but popular choice.
AB  - Current methods of contact tracing are only partially effective. Patient
      delivered partner medication (PDPM), in which patients are dispensed antibiotics
      for their sexual partner(s), has been shown to reduce persistent and recurrent
      infections. We performed a questionnaire to canvass opinions of UK staff and
      patients about PDPM. The response rate was 72% (88/122) for staff and 90%
      (473/525) for patients. The majority of staff (81%) thought that PDPM would be
      acceptable to patients, and should be combined with written information and a
      recommendation to attend a clinic. Patients were mostly (59%) in favour of PDPM,
      87% thought it would make it easier to abstain from sex during treatment, and 94%
      indicated that after being given antibiotics by a partner, they would attend a
      clinic for tests. Concerns expressed by staff and patients included drug
      allergies, potential lack of information provided to partners, management of
      complicated infection, pregnancy and medicolegal implications.

PMID- 18073016
TI  - HIV-1 genotype after interruption of non-nucleoside reverse transcriptase
      inhibitor-based antiretroviral therapy and virological response after resumption
      of the same regimen.
AB  - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have a longer half-life
      than nucleoside reverse transcriptase inhibitor (NRTIs). Simultaneous
      interruption of all drugs exposes the patients to NNRTI monotherapy. This study
      evaluated HIV-1 genotype after treatment interruption (TI) of NNRTI-based
      antiretroviral therapy (ART) and virological response after resumption of the
      same ART regimen. A prospective study was conducted in HIV-1-infected patients
      who enrolled into a CD4-guided TI study. All patients continued dual NRTIs for a
      further 7-10 days at NNRTI TI. HIV-1 genotypic assay was performed prior to
      resumption of the same ART regimen. Forty-three patients required ART resumption
      after TI from NNRTI-based regimens. Mean age was 42.7 years; 44% were men. Median
      CD4 and HIV-1 RNA at the time of ART resumption were 178 cell/mm(3) and 5.78 log
      copies/mL, respectively. HIV-1 genotype revealed no mutations contributed to NRTI
      or NNRTI resistance. Of all, 56% and 100% patients achieved undetectable HIV-1
      RNA at three and six months, respectively. Median CD4 were 386 and 419
      cells/mm(3) at the corresponding periods. In conclusion, continuation of dual
      NRTIs for 7-10 days after TI of NNRTI-based regimens can minimize the risk of
      acquired NNRTI resistance. With this strategy, the same regimen can be used for
      resumption and also yield good virological and immunological outcomes.

PMID- 18073017
TI  - Leucocyte esterase testing of first-voided urine and urethral and cervical smears
      to identify Mycoplasma genitalium-infected men and women.
AB  - Leucocyte esterase (LE) in first-voided urine (FVU) and presence of leucocytes in
      urethral and cervical smears were evaluated to identify Mycoplasma genitalium
      infection in 416 men and 417 women attending Department of Genitourinary
      Medicine. M. genitalium was diagnosed in FVU specimens by realtime polymerase
      chain reaction. The prevalence of M. genitalium was 6.5% in women and 6.7% in
      men. In total, 88.5% (23/26) of M. genitalium-infected men were identified by a
      combination of urethral smear and the LE test. In women, the combination of
      urethral and/or cervical smears and/or a positive LE test identified 91.3%
      (21/23) of M. genitalium-infected patients. Organism load in FVU correlated
      significantly with presence of urethritis (> or =4 leucocytes per high-power
      field) in men. A combination of LE testing of urine and urethral and/or cervical
      smears can be used as screening tests to select patients for specific M.
      genitalium testing. By this strategy, about 10% of infected individuals will
      remain undetected.

PMID- 18073018
TI  - Repeated human papillomavirus DNA findings among female university students.
AB  - In a previous study, we found a high (33%) human papillomavirus (HPV) DNA
      prevalence among first year university students in the Helsinki metropolitan
      area. We have now performed HPV rescreening among first-round HPV-positive
      students using a liquid-based hybridization assay. A total of 212 students
      participated in rescreening, and 82 (38.7%) of 212 were found to be positive for
      HPV DNA. Low-risk (lr) HPV DNA was repeatedly found in 16.8% of the patients who
      had been lr positive in the first screening round. High-risk (hr) HPV DNA was
      repeatedly found in 33.3% of the patients. Although HPV typing in these samples
      has not been carried out yet, we conclude that repeatedly positive HPV DNA
      findings were strikingly common. hrHPV DNA was repeatedly found twice as often as
      lrHPV DNA. HPV DNA prevalence was higher among oral contraceptive users than
      among patients using other contraception.

PMID- 18073019
TI  - Detection of Treponema pallidum sp pallidum DNA in latent syphilis.
AB  - In this study, polymerase chain reaction (PCR) techniques were used to detect
      Treponema pallidum DNA in samples from patients with latent syphilis. Sixty-nine
      patients with latent syphilis and 18 with treated syphilis were included. Whole
      blood, plasma, sera and ear scrapings, totalling 235 samples from patients with
      latent syphilis, were obtained. Three PCR assays (47-PCR, polA-PCR and M-PCR
      assays) were performed. The 47-PCR yielded the highest number of positive samples
      -92/235 (39.1%), followed by M-PCR -90/235 (38.3%) and polA-PCR -73/235 (31.1%).
      Ear scrapings presented the highest number of positives (47/84 -56%), followed by
      plasma samples (36/84 -42.9%), whole blood (32/84 -38.1%) and sera (21/84 -25%).
      In conclusion, we have confirmed that T. pallidum can be found in blood of
      patients with latent syphilis. The 47-PCR technique was found to be the most
      sensitive, whereas ear lobe scrapings seem to be the best specimen for detection
      of T. pallidum DNA in latent syphilis.

PMID- 18073020
TI  - Process, efficacy and sample demographics of three approaches to behavioural
      surveillance for gonorrhoea: case interviews, place surveys, and network studies.
AB  - We investigated the process and time required to collect 450 interviews in a
      project to determine the most efficacious behavioural surveillance approaches to
      detect changes in gonorrhoea prevalence. In total, 150 respondents were recruited
      in each method. For each of place surveys (bars), gonorrhoea case interviews, and
      network studies based on seeds from the case and place interviews, we determined
      the recruitment rate and process. Urine testing for gonorrhoea and chlamydia took
      place in the place interviews. We present data from Houston, Texas that
      illustrate the sample characteristics, recruitment rates, and, where appropriate,
      infection rates. Data indicate that there was high uptake and a rapid recruitment
      rate from the place surveys, an intermediate rate from the network studies, and
      that the gonorrhoea case interviews were the most inefficient accrual method for
      behavioural surveillance. Sample characteristics and biases in each method are
      described, and conclusions drawn for the relative efficacy of each method for
      gonorrhoea behavioural surveillance.

PMID- 18073021
TI  - A comparison of the effectiveness of lipid-lowering therapy between HIV- and non
      HIV-infected subjects with hyperlipidaemia.
AB  - This retrospective cohort study conducted at the Durham Veterans Affairs Medical
      Center evaluated the effectiveness and safety of lipid-lowering therapy (LLT) in
      a HIV-infected population as compared with a general population with
      hyperlipidaemia. Fifty-three HIV-infected subjects who developed dyslipidaemia
      and 53 age-matched non-HIV-infected subjects receiving LLT were selected.
      Efficacy of LLT was assessed after three and six months. Non-HIV-infected
      subjects were more likely to achieve total cholesterol (TC) goals at three and
      six months (P = 0.045, P = 0.005) and triglyceride (TG) goals at six months (P =
      0.017). Less than 45% of HIV-infected subjects met National Cholesterol Education
      Program Adult Treatment Panel III (NCEP ATP III) goals at three or six months.
      While non-HIV-infected subjects were more likely to achieve TC and TG goals than
      HIV-infected subjects, overall achievement of NCEP III goals was poor. This
      result was likely due to treatment with inappropriately low doses of statins.

PMID- 18073022
TI  - Early detection of subclinical HIV sensory polyneuropathy using intraepidermal
      nerve fibre density quantification: association with HIV stage and surrogate
      markers.
AB  - The linear intraepidermal nerve fibre density (IENFD) and secondary branching
      were evaluated from skin biopsy of both the distal calf and the proximal thigh
      after staining with protein gene product 9.5 in 94 individuals of an HIV
      outpatient cohort. Possible correlations with clinical and electrophysiological
      evidence of distal sensory polyneuropathy (DSP), patients' demographics,
      antiretroviral history and HIV surrogate markers were analysed. Reduced IENFD was
      recognized in the majority of this population (mean +/- standard deviation [SD]
      IENFD in the calf and the thigh was 3.19 +/- 1.91 and 7.07 +/- 3.5 fibres/mm,
      respectively). One-third of the patients with low IENFD had no clinical or
      electrophysiological evidence of DSP. The level of prior immunosuppression as
      expressed by lower nadir CD4 count, more advanced HIV stage and prior exposure to
      combinations of neurotoxic antiretrovirals was associated with more decreased
      IENFD. Increased SB was associated with symptomatic DSP.

PMID- 18073023
TI  - Chlamydia screening or prophylaxis before laparoscopy and dye hydrotubation: no
      readmissions, no worry, or is that so?
AB  - We present a retrospective analysis of 120 laparoscopy and dye hydrotubation
      procedures. Our aim was to assess chlamydia screening or prophylaxis before, and
      the rate of readmission after, such procedures. We found evidence of a chlamydia
      screening test performed in 109 cases. Of the 37 women where antibiotic cover
      should have been considered, only 18 were treated. There were no readmissions for
      suspected pelvic inflammatory disease or for other complications. Our study may
      not have demonstrated any acute clinical recurrences, but there is a potential
      for subclinical reactivation or for delayed clinical recurrence leading to tubal
      damage in the untreated women.

PMID- 18073024
TI  - Neonatal herpes in herpes simplex virus type 2 and HIV-seropositive pregnant
      patients; the role of preventive measures in the absence of clinical disease of
      herpes.
AB  - There is very little knowledge about how herpes simplex virus (HSV)
      seropositivity of HIV-positive mothers could complicate the occurrence of
      neonatal herpetic disease, in the absence of genital ulcers, in this group of
      patients. We present a case of fatal disseminated neonatal herpes infection in a
      baby, born to a HIV-positive patient, and wish to discuss the potential need for
      changes in the management of this group of patients during pregnancy.
      Disseminated HSV disease is a rare, yet serious condition in newborns of HSV
      infected mothers, and women with HIV infection have shown to frequently shed more
      HSV DNA in their genital secretions, even in the absence of active herpetic
      ulcers. This is the first case report of this rare association and, as a result,
      the evidence in support of our hypothesis has been extrapolated from other
      studies.

PMID- 18073025
TI  - Papular acantholytic dyskeratosis presenting as genital warts.
AB  - A 24-year-old woman presented with genital warts which did not respond to
      treatment. Biopsy confirmed changes in keeping with a diagnosis of Darier's
      disease. The patient, however, had no other manifestations of Darier's disease,
      i.e. family history of skin disease, nail changes or other skin site involvement.
      We propose that this patient has a form of Darier's disease called genital
      papular acantholytic dyskeratosis.

PMID- 18073026
TI  - Things that go bump on the right.
AB  - Groin masses are common and the differential diagnosis is wide. It is important
      to distinguish surgical and medical causes. A rare surgical cause--that may be
      associated with cryptorchidism--is presented here.

PMID- 18073027
TI  - Comparison of APTIMA COMBO 2 assay with polymerase chain reaction Roche assay for
      detection of Chlamydia trachomatis in endocervical swabs.

PMID- 18073043
TI  - Art as a scientific object: toward a visual science of art.

PMID- 18073044
TI  - Some principles of spatial organization in art.
AB  - Rules of composition in paintings form a rich probe into the principles of
      perceptual processing that have been discussed for centuries. These principles
      can be studied by controlled scientific experiments, but an alternative approach
      is to use the art works themselves as a database for direct analysis. This paper
      focuses on the analysis of composition in relation to the canvas frame. An
      underlying principle is the compositional pyramid rising from the bottom of the
      frame to a center of consciousness high on the midline, which also finds its
      expression in the configuration of portrait paintings. The analyses presented
      reveal a dominant positioning principle for one eye in a portrait to lie on the
      vertical axis with an unbiased accuracy of the order of +/-5%. Analysis of the
      vertical location shows that the dominant height is at or above the Golden
      Section level on the vertical axis. In general, the layout of the portrait
      follows the principle of the compositional pyramid, with a center of
      consciousness at its apex, but there are many other compositional principles at
      work in the corpus of portraits in general. Analysis of the portraits of
      particular artists reveals that special features of their work must be considered
      in order to identify those that do and do not conform to the eye-centering
      principle.

PMID- 18073045
TI  - The origins of entasis: illusion, aesthetics or engineering?
AB  - A typical characteristic of columns in Doric temples is entasis; a slight
      convexity in the body of a column. Often, and particularly in guide-books, it is
      suggested that entasis is intended to compensate for an illusion of concavity in
      columns with truly straight sides. We have investigated whether any such visual
      illusion exists, both in parallel sided and in tapering columns in a series of
      experiments, finding little evidence to support any illusion-compensation theory.
      Further, we explored the possibility that entasis was employed for purely
      aesthetic reasons, but the results do not support this conclusion. Finally,
      evidence supporting an engineering role for entasis is presented.

PMID- 18073046
TI  - Designing visually rich, nearly random textures.
AB  - Camouflaging textures containing as in real life edges at all orientations, were
      designed by computer, then manually, for use in stereoscopic vision studies. In
      the manual procedure, the starting point is either a set of photographs (for
      instance, of barks) or a manually produced first-generation texture. Then patches
      are cut zigzagging and assembled into successive generations of textures. The
      absence of extended edges--straight or curved--and the local heterogeneity of the
      texture are important camouflaging factors, allowing curved surfaces to be
      covered with these textures without visible join. Small areas of a texture often
      suggest a scene, but when the areas are assembled, the suggestive power is lost,
      and the statistical properties of the texture then dominate. However, when
      symmetry is introduced (as in the Rorschach test), meaningful scenes emerge
      again.

PMID- 18073048
TI  - Piranesi and the infinite prisons.
AB  - Piranesi was an extraordinarily talented artist who came to be considered the
      best known engraver and etcher of the 18th century. He spent his lifetime
      recording the magnificent buildings and ruins of ancient Rome. In his earlier
      work, he developed architectural fantasies and dark visions of imaginary prisons,
      the Carceri d'Invenzione (Imaginary Prisons), which have fascinated people ever
      since they first appeared. They also made an impact in later artistic and
      literary contexts. Today they are considered the best expression of bewilderment,
      of the world's massive oppression of man. How did Piranesi generate such a
      powerful source of meaning? I have reviewed a number of contributions by art
      essayists in the search for what lies behind the fascination of the 'Carceri'.
      Analysis of these texts provides a rich set of aesthetic and psychological
      attributes as well as detailed indications of where to seek the source of the
      meanings. I suggest here a fruitful integration of this analysis, developed by
      considering various particular perceptual and geometric cues. I discuss three
      possible sources of meaning: the combination of architectural elements out of
      proportion; the difficulty of building a unitary space; and the 'bottom
      perspective' that gives rise to a sensation of floating.

PMID- 18073049
TI  - Gender's effect on the hemispheric laterality of Rembrandt's portraits.
AB  - In 64% of Rembrandt's female portraits the poser's left-cheek faces the viewer.
      However, this occurs in only 33% of his male portraits. This asymmetry is
      consistent with viewers rating Rembrandt's left-cheeked male portraits as likely
      to be avoided, which may reflect that aggressive displays of dominance are
      governed by the contralateral right-hemisphere, while rating left-cheeked female
      faces as likely to be approached may indicate sexual attractiveness. Rembrandt's
      exposed-cheek gender difference paints both sexual selection and dominance as
      being governed by the right cerebral hemisphere.

PMID- 18073050
TI  - Artful visions.
AB  - Visual artists and visual scientists are often concerned with examining the same
      spatial phenomena, but the methods they adopt differ radically. Scientists try to
      discover new facts regarding old phenomena; they rarely discover new phenomena
      but different conditions under which the old ones operate (perhaps using some
      novel apparatus for generating stimuli). Artists are concerned with arranging
      phenomena in a manner that has not been seen before, or perhaps to increase the
      spectators' awareness of the phenomena. This typically involves complicating the
      effects rather than simplifying pattern elements. Thus, scientists rarefy and
      isolate phenomena to control them in the laboratory, whereas artists embrace
      complexity and manipulate phenomena intuitively. The differences in method have
      resulted in divergent vocabularies for describing similar effects, and the two
      approaches can appear more disparate than their phenomenal commonality would
      suggest. It could be argued that for spatial vision, prior to the advent of
      computer graphics, visual scientists have not represented adequately the subject
      matter of their own enquiry; this want was supplied by visual artists. Not only
      have artists provided more engaging examples of spatial phenomena, but they have
      also enhanced their range in ways that are scientifically novel. The opposite
      argument applies to motion perception, where scientists developed techniques that
      were eagerly adopted in the arts. The interactions between art and both spatial
      and motion vision were influenced by instruments invented in the early nineteenth
      century for manipulating the representation of space and time - the stereoscope
      and the stroboscopic disc.

PMID- 18073051
TI  - Visual interest in pictorial art during an aesthetic experience.
AB  - Two experiments were performed during which adults untrained in the visual arts
      were shown digital versions of eight paintings by renowned artists. In Experiment
      1 participants' written reactions following a single 100 ms glance at each work
      were found to overwhelmingly reflect an initial holistic impression (i.e. gist)
      of the structural arrangement and semantic meaning of the paintings. In the
      second experiment participants' eye movements and verbal reactions were recorded
      as they evaluated each reproduction for pleasingness. Analyses reveal the
      relationships between the content and structural organization of the art stimuli
      and the way viewers select, process and think about information contained in
      paintings across the time course of an aesthetic experience. The results are
      interpreted in terms of an information-processing stage model of visual
      aesthetics according to which perceptual-cognitive processing of an art stimulus
      begins with the rapid generation of a gist reaction followed by scrutiny of
      pictorial features directed in a top-down fashion by cognitively-based evaluative
      processes.

PMID- 18073052
TI  - Art pieces that 'move' in our minds--an explanation of illusory motion based on
      depth reversal.
AB  - Certain art forms, such as Patrick Hughes's 'reverspectives', Dick Termes's
      'Termespheres', intaglios, and hollow masks, appear to move vividly as viewers
      move in front of them, even though they are stationary. This illusory motion is
      accompanied by a perceived reversal of depth, where physical convex and concave
      surfaces are falsely seen as concave and convex, respectively. A geometric
      explanation is presented that considers this illusory motion as a result of the
      perceived depth reversal. The main argument is that the visual system constructs
      a three-dimensional representation of the surfaces, and that this representation
      is one of the sources that contribute to the illusory motion, together with
      vestibular signals of self-motion and signals of eye movements. This explanation
      is extended to stereograms that are also known to appear to move as viewers move
      in front of them. A quantitative model can be developed around this geometric
      explanation to examine the extent to which the visual system tolerates large
      distortions in size and shape and still maintains the illusion.

PMID- 18073053
TI  - A universal model of esthetic perception based on the sensory coding of natural
      stimuli.
AB  - Philosophers have pointed out that there is a close relation between the
      esthetics of art and the beauty of natural scenes. Supporting this similarity at
      the experimental level, we have recently shown that visual art and natural scenes
      share fractal-like, scale-invariant statistical properties. Moreover, evidence
      from neurophysiological experiments shows that the visual system uses an
      efficient (sparse) code to process optimally the statistical properties of
      natural stimuli. In the present work, a hypothetical model of esthetic perception
      is described that combines both lines of evidence. Specifically, it is proposed
      that an artist creates a work of art so that it induces a specific resonant state
      in the visual system. This resonant state is thought to be based on the
      adaptation of the visual system to natural scenes. The proposed model is
      universal and predicts that all human beings share the same general concept of
      esthetic judgment. The model implies that esthetic perception, like the coding of
      natural stimuli, depends on stimulus form rather than content, depends on higher
      order statistics of the stimuli, and is non-intuitive to cognitive introspection.
      The model accommodates the central tenet of neuroesthetic theory that esthetic
      perception reflects fundamental functional properties of the nervous system.

PMID- 18073054
TI  - Portraits and perception: configural information in creating and recognizing face
      images.
AB  - Configural information has long been considered important for face recognition.
      However, traditional portraiture instruction encourages the artist to use a
      'generic' configuration for faces rather than attempting to replicate precise
      feature positions. We examine this intriguing paradox with two tasks designed to
      test the extent to which configural information is incorporated into face
      representations. In Experiment 1, we use a simplified face production task to
      examine how accurately feature configuration can be incorporated in the generated
      likenesses. In Experiment 2, we ask if the 'portraits' created in Experiment 1
      are discriminable from veridical images. The production and recognition results
      from these experiments show a consistent pattern. Subjects are quite poor at
      arranging facial features (eyes, nose and mouth) in their correct locations, and
      at distinguishing erroneous configurations from correct ones. This seeming
      insensitivity to configural relations is consistent with artists' practice of
      creating portraits based on a generic geometric template. Interestingly, the
      frame of reference artists implicitly use for this generic template - the
      external face contour - emerges as a significant modulator of performance in our
      experimental results. Production errors are reduced and recognition performance
      is enhanced in the presence of outer contours. We discuss the implications of
      these results for face recognition models, as well as some possible perceptual
      reasons why portraits are so difficult to create.

PMID- 18073055
TI  - Fractal-like image statistics in visual art: similarity to natural scenes.
AB  - Both natural scenes and visual art are often perceived as esthetically pleasing.
      It is therefore conceivable that the two types of visual stimuli share
      statistical properties. For example, natural scenes display a Fourier power
      spectrum that tends to fall with spatial frequency according to a power-law. This
      result indicates that natural scenes have fractal-like, scale-invariant
      properties. In the present study, we asked whether visual art displays similar
      statistical properties by measuring their Fourier power spectra. Our analysis was
      restricted to graphic art from the Western hemisphere. For comparison, we also
      analyzed images, which generally display relatively low or no esthetic quality
      (household and laboratory objects, parts of plants, and scientific
      illustrations). Graphic art, but not the other image categories, resembles
      natural scenes in showing fractal-like, scale-invariant statistics. This property
      is universal in our sample of graphic art; it is independent of cultural
      variables, such as century and country of origin, techniques used or subject
      matter. We speculate that both graphic art and natural scenes share statistical
      properties because visual art is adapted to the structure of the visual system
      which, in turn, is adapted to process optimally the image statistics of natural
      scenes.

PMID- 18073056
TI  - Statistical regularities of art images and natural scenes: spectra, sparseness
      and nonlinearities.
AB  - Paintings are the product of a process that begins with ordinary vision in the
      natural world and ends with manipulation of pigments on canvas. Because artists
      must produce images that can be seen by a visual system that is thought to take
      advantage of statistical regularities in natural scenes, artists are likely to
      replicate many of these regularities in their painted art. We have tested this
      notion by computing basic statistical properties and modeled cell response
      properties for a large set of digitized paintings and natural scenes. We find
      that both representational and non-representational (abstract) paintings from our
      sample (124 images) show basic similarities to a sample of natural scenes in
      terms of their spatial frequency amplitude spectra, but the paintings and natural
      scenes show significantly different mean amplitude spectrum slopes. We also find
      that the intensity distributions of paintings show a lower skewness and
      sparseness than natural scenes. We account for this by considering the range of
      luminances found in the environment compared to the range available in the medium
      of paint. A painting's range is limited by the reflective properties of its
      materials. We argue that artists do not simply scale the intensity range down but
      use a compressive nonlinearity. In our studies, modeled retinal and cortical
      filter responses to the images were less sparse for the paintings than for the
      natural scenes. But when a compressive nonlinearity was applied to the images,
      both the paintings' sparseness and the modeled responses to the paintings showed
      the same or greater sparseness compared to the natural scenes. This suggests that
      artists achieve some degree of nonlinear compression in their paintings. Because
      paintings have captivated humans for millennia, finding basic statistical
      regularities in paintings' spatial structure could grant insights into the range
      of spatial patterns that humans find compelling.

PMID- 18073057
TI  - Examining art: dissociating pattern and perceptual influences on oculomotor
      behaviour.
AB  - When observing art the viewer's understanding results from the interplay between
      the marks made on the surface by the artist and the viewer's perception and
      knowledge of it. Here we use a novel set of stimuli to dissociate the influences
      of the marks on the surface and the viewer's perceptual experience upon the
      manner in which the viewer inspects art. Our stimuli provide the opportunity to
      study situations in which (1) the same visual stimulus can give rise to two
      different perceptual experiences in the viewer, and (2) the visual stimuli differ
      but give rise to the same perceptual experience in the viewer. We find that
      oculomotor behaviour changes when the perceptual experience changes. Oculomotor
      behaviour also differs when the viewer's perceptual experience is the same but
      the visual stimulus is different. The methodology used and insights gained from
      this study offer a first step toward an experimental exploration of the relative
      influences of the artist's creation and viewer's perception when viewing art and
      also toward a better understanding of the principles of composition in
      portraiture.

PMID- 18073058
TI  - The science and craft of autostereograms.
AB  - Autostereograms or SIRDS (Single Image Random-Dot Stereograms) are camouflaged
      stereograms which combine the Julesz random-dot stereogram principle with the
      wallpaper effect. They can represent any 3D shape on a single image having a
      quasi-periodic appearance. Rather large SIRDS can be interpreted in depth with
      unaided eyes. In the hands of computer graphic designers, SIRDS spread all over
      the world in 1992-1994, and these images, it was claimed, opened a new era of
      stereoscopic art. Some scientific, algorithmic and artistic aspects of these
      images are reviewed here. Scientifically, these images provide interesting cues
      on stereoscopic memory, and on the roles of monocular regions and texture
      boundaries in stereopsis. Algorithmically, problems arising with early SIRDS,
      such as internal texture repeats or ghost images are evoked. Algorithmic
      recommendations are made for gaining a better control on the construction of
      SIRDS. Problems of graphic quality (smoothness of the represented surfaces, or
      elimination of internal texture repeats) are discussed and possible solutions are
      proposed. Artistically, it is proposed that SIRDS should become less anecdotal,
      and more oriented towards simple geometric effects, which could be implemented on
      large panels in natural surrounds.

PMID- 18073059
TI  - [Interferons 50 years and liver diseases].

PMID- 18073060
TI  - [Liver transplantation for chronic hepatitis B patients with lamivudine
      monotherapy or lamivudine combined with individualized low-dose hepatitis B
      immunoglobulin treatment].
AB  - OBJECTIVE: The aim of this study was designed to evaluate the outcomes of liver
      transplant recipients with chronic hepatitis B (CHB) receiving either lamivudine
      monotherapy or lamivudine combined with individualized low-dose hepatitis B
      immunoglobulin (HBIG) therapy. METHODS: A total of 111 liver transplant
      recipients with CHB were divided not randomly into two groups according to the
      availability of HBIG before liver transplantation (LT). Thirty-two patients
      received lamivudine monotherapy (100 mg/d) and 79 patients received lamivudine
      (100 mg/d) combined with individualized low-dose HBIG (intramuscular
      administration) to maintain the titer of antibody to hepatitis B virus (HBV)
      surface antigen (anti-HBs) not less than 100 U/L. The patients were followed-up
      for a median time of 32 months (1 to 88 months). RESULTS: In the lamivudine
      monotherapy group, 5 patients hepatitis B relapsed (3/5 developed YMDD mutants of
      HBV), with 1-, 2-, and 3-year cumulative recurrence rates of 7.1%, 14.3% and
      17.9% and survival rates of 87.5%, 84.4% and 74.6%. In the lamivudine and HBIG
      combination therapy group, 2 patients hepatitis B relapsed (2/2 developed YMDD
      mutants of HBV), with 1-, 2-, and 3-year cumulative recurrence rates of 0, 1.8%
      and 5.7% (P < 0.01) and survival rates of 83.5%, 80.9% and 77.6% (P > 0.05).
      CONCLUSIONS: Compared with lamivudine monotherapy, lamivudine combined with
      individualized low-dose HBIG can further reduce the recurrence risk of hepatitis
      B in liver transplant recipients. This combined therapy could be used as a
      rational strategy for prophylaxis of hepatitis B recurrence in such patients.

PMID- 18073061
TI  - [A clinical analysis of HBV reactivation in patients with malignant tumors].
AB  - OBJECTIVE: To observe the anti-viral therapy effect on HBV reactivation in
      malignant tumor patients and hepatitis B virus carriers after their cancer
      chemotherapy. METHODS: Thirteen cancer patients but also chronic hepatitis B
      virus carriers were enrolled in this study. They were randomly put into two
      groups. Eight patients were put in the therapeutic group. They all had abnormal
      liver functions induced by the reactivation of HBV after their cancer
      chemotherapy. Then they were treated with lamivudine. The other 5 cases were
      treated with lamivudine before their cancer chemotherapy when their serum HBV DNA
      levels were less than 10(3) copies/ml (preventive therapeutic group). The two
      groups were followed-up with liver function tests and serum HBV DNA level
      measurements. RESULTS: Among the 8 cases of the therapeutic group, 5 cases died
      of liver failure; cancer chemotherapy was postponed or even terminated in 3
      patients due to liver function abnormality and anti-virus treatment was started.
      In the preventive therapy group, no HBV reactivation was observed in any of the 5
      cases. CONCLUSION: For HBV carrier cancer patients, an anti-viral therapy before
      their cancer chemotherapy seems to be very important.

PMID- 18073062
TI  - [Serum level of HMGB1 in patients with hepatitis B and its clinical
      significance].
AB  - OBJECTIVE: To investigate whether there is a possible role of pro-inflammatory
      cytokine high mobility group box protein 1 (HMGB1) causing liver failure in
      severe hepatitis B patients. METHODS: Serum HMGB1 levels of chronic hepatitis B
      (CHB) patients with different clinical conditions were measured and the
      correlations between HMGB1 and TBil or PTA were analyzed. (1) 54 chronic
      hepatitis B patients in different clinical conditions were enrolled in our study.
      Their serum TBil and PTA levels were detected by routine methods. (2) Their serum
      HMGB1 levels were also detected. 100 KD super-filtration columns were used to get
      rid of large proteins in the serum and 10 KD columns were used to condense the
      protein. Western blot was used to determine HMGB1 levels, and correlations
      between HMGB1 and TBil or PTA were analyzed. RESULTS: The detection rates of
      serum HMGB1 were 100% (23/23), 90% (9/10), and 55% (6/11) in 23 patients with
      hepatic failure, 10 patients with chronic severe hepatitis B, and 11 patients
      with chronic moderate hepatitis B respectively. The concentration of serum HMGB1
      levels in these three groups was (83.4+/-21.3), (78.1+/-19.5) and (60.3+/-14.3)
      microg/L respectively. Serum HMGB1 was not detected in normal healthy controls
      and hardly detected in convalescent and mild hepatitis patients. There were
      positive correlations between HMGB1 and TBil and negative correlations between
      HMGB1 and PTA. CONCLUSION: HMGB1 levels in serum were closely associated with
      disease severity in chronic hepatitis B patients. HMGB1 may play a key role in
      the pathogenesis of chronic severe hepatitis B and liver failure.

PMID- 18073063
TI  - [Preparation and application of oligo microarrays for hepatitis virus detection
      and genotyping].
AB  - OBJECTIVE: To prepare oligo microarrays for hepatitis virus detection and
      genotyping. METHODS: By analyzing the DNA or cDNA of HBV, HDV and 4 different
      genotypes of HCV with the BLAST program, a group of specific sequences for the
      candidate probes was specified. Array Designer 3.0 software was applied to
      analyze the candidates to select probes with high specificity, identical length
      and similar melting temperature (Tm). Altogether 16, 8 and 68 oligonucleotide
      probes were designed for diagnosis of HBV, HDV, and genotyping HCV. Following the
      synthesizing and purification, oligo probes were deposited on oligonucleotide
      chips as microarrays for hepatitis virus detection and genotyping. The samples
      were labeled by RD-PCR method. Hybridization results were analyzed to cross out
      those probes with low specificity and sensitivity, and those with signal to noise
      ratios (SNR) less than 4.0. RESULTS: Two types of gene chips were successfully
      developed: microarrays for HBV and HDV simultaneous detection and for HCV
      genotyping. CONCLUSION: Using oligo probes to construct gene chips for clinical
      diagnosis of hepatitis virus is a simple and effective method. It may be widely
      used in detecting hepatitis viruses and their genotyping in clinical settings.

PMID- 18073064
TI  - [A clinical study of adefovir dipivoxil treatment for chronic hepatitis patients
      with cirrhosis in their decompensation period].
AB  - OBJECTIVE: To evaluate the efficacy and safety of 48 weeks adefovir dipivoxil
      (ADV) treatment for chronic hepatitis patients with cirrhosis in their
      decompensation period. METHODS: Sixty-two chronic hepatitis patients with
      cirrhosis in their decompensation period were randomly put into two groups. An
      adefovir dipivoxil (ADV) group: 32 patients treated with 10 mg of ADV a day; and
      a lamivudine (LMV) group: 30 patients treated with 100 mg of LMV a day. The
      course of treatment lasted 48 weeks. Serum levels of alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), Alb, TBil, HBeAg, HBV DNA, PCIII, IVC,
      LN, and HA, renal function, Child-Pugh scores and drug adverse reactions during
      the treatment of the two groups were checked, compared and analyzed. RESULTS: The
      ratios of recovery for liver functions and the negativity rate of HBV DNA, HBeAg,
      including sero-conversion rate of HBeAg/HBeAb, were increased with prolongation
      of the treatment period; however, the differences between the two groups were not
      statistically significant (P > 0.05). Two patients treated with lamivudine
      suffered from YMDD variation at the 48th week; the ratio of variation was 6.7%.
      No YMDD variation happened in the ADV group. On the 24th week of the treatment,
      the levels of the serum markers of hepatic fibrosis declined obviously, compared
      with those prior to the treatment (P < 0.01). There were no significant
      statistical differences of those levels between the two groups (P > 0.05). No
      significant differences of Child-Pugh scores were noticed between the two groups
      (P > 0.05). No drug related renal function impairment was found during the
      treatment. Two patients of each group had adverse drug reactions but all were
      mild. CONCLUSION: The efficacy and safety of adefovir dipivoxil and lamivudine
      treatment for the above patients were similar, but the ratio of emerging virus
      resistant strains was lower in the adefovir dipivoxil treatment group.

PMID- 18073065
TI  - [Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma
      and their significance in clinical settings].
AB  - OBJECTIVES: To identify serologic markers that may indicate the early presence of
      hepatocellular carcinoma (HCC), and analyze their significance in the
      pathogenesis of chronic hepatitis B. METHODS: Hepatitis B x antigen (HBxAg)
      positive and negative HepG2 cells were subjected to PCR select cDNA subtraction
      to identify differentially expressed genes that may precede the development of
      HCC. These included the up-regulated genes URG4, URG7, URG11, and VEGFR3, and the
      down-regulated gene, Sui1. Specific ELISAs were constructed to measure
      differentially expressed antigens and their corresponding antibodies to determine
      whether they had prognostic and/or diagnostic value. The study population
      consisted of 730 people. Among them, 416 were HBsAg(-) and 298 were HBV carriers
      with chronic liver disease and/or HCC. In addition, 16 patients had non-viral
      hepatitis. Among these, serial serum samples from 53 HBsAg(+) patients with
      cirrhosis were collected and studied. RESULTS: Antibodies to multiple
      differentially regulated genes were detectable in serum samples from patients
      with HBV associated cirrhosis and HCC, but not in serum samples from uninfected
      individuals (P < 0.01). Antibodies were undetectable in serum samples from HBV
      patients without liver disease and in serum samples from patients with other
      tumor types, and among those with non viral hepatitis. Among patients at high
      risk of developing HCC, these antibodies were found to be independent of
      nationality and ethnicity. Statistical analysis of the 28 HBsAg(+) patients with
      HCC showed that anti-URG11 and anti-VEGFR3 were the most frequently detected
      antibodies. These antibodies were found to coexist in 16 (P < 0.05). In contrast,
      among the 25 HBsAg(+) patients without HCC, anti-Sui1 and anti-URG7 were the most
      prevalent antibodies. These antibodies coexisted in 11 (P < 0.05). In addition,
      HCC patients with four or more antibodies detected before the appearance of HCC
      had a poorer survival outcome. CONCLUSION: These antibodies can be detected in
      serum samples several months to several years before the appearance of HCC. This
      suggests that they may be preneoplastic markers that may help to distinguish
      which HBV carriers with cirrhosis are most likely to progress and develop HCC.

PMID- 18073066
TI  - [Pulmonary infection and its risk factors after orthotopic liver
      transplantation].
AB  - OBJECTIVES: To investigate the characteristics of pulmonary infection and its
      risk factors after orthotopic liver transplantation (OLT). METHODS: Clinical data
      of 250 cases having liver transplantations from April 2001 to August 2005 were
      retrospectively studied in order to analyse the differences between patients with
      and without pulmonary infection. RESULTS: Fifty-seven (57/250, 22.8%) recipients
      had 72 episodes of pulmonary infection after liver transplantation. Bacterial
      infection was the most common followed by fungal infection (13/72, 18.1%), and
      cytomegalovirus infection (12/72, 16.7%). There were 36 episodes of pulmonary
      infection caused by one kind of bacteria, 5 episodes by two kinds of bacteria and
      6 episodes by multiple kinds of bacteria. Seven episodes of fungal infection were
      accompanied with bacterial infection, and three episodes of cytomegalovirus
      infection were accompanied with bacterial infection simultaneously. The 1-, 2-
      and 3- year survival rates were 71.9%, 61.4%, and 53.4% of the patients with
      pulmonary infection and 93.1%, 75.8%, and 67.2% of those without the infection.
      Logistic regression analysis suggested that preoperative infection, mechanical
      ventilation > 12 hours, a long duration of the operation, total volume of blood
      transfusion during operation >1000 ml, reoperation after OLT, postoperative
      pleural effusion and the duration of stay in the intensive care unit were
      independent risk factors of pulmonary infection after OLT. CONCLUSION: Bacterial
      infections were the main pulmonary infection after OLT and the infections caused
      by multiple pathogens or multiple-antibiotic-resistant bacteria were seen more
      frequently. The risk factors of pulmonary infection should be controlled to
      decrease the infection rate after OLT. It is important to make a correct
      diagnosis for pulmonary infection after OLT and use appropriate antibiotics as
      soon as possible.

PMID- 18073067
TI  - [The relationship between the opening of mitochondrial permeability transition
      pores of cultured hepatocytes with their apoptoses in a non-alcoholic fatty liver
      disease model].
AB  - OBJECTIVE: To investigate the opening of the mitochondrial permeability
      transition pores of the cultured hepatocytes in a non-alcoholic fatty liver
      disease model and its relationship with apoptosis of the cells. METHODS: Oleic
      acid was used to induce cultured L02 hepatocyte steatotic in making a model of
      NAFLD. The steatotic hepatocytes were detected with oil red O staining; the
      opening of the mitochondrial permeability transition pores was observed under a
      fluorescence microscope. The apoptosis of the cells was detected with a flow
      cytometer. RESULTS: After adding oleic acid to the cultured hepatocytes, a model
      of steatosis of human hepatocytes was established after 24 hours. Oleic acid
      opened the mitochondrial permeability transition pores of the L02 hepatocytes
      (72.58%+/-2.78%) more than that in the control group (8.28%+/-4.98%) and the
      difference was statistically significant (P < 0.01). Apoptosis index of the
      steatotic hepatocytes at 24 hours and 48 hours were 11.09%+/-4.95% and 15.24%+/
      2.45%. They were also higher than those of the control group (4.56%+/-1.25%) (P <
      0.05, P < 0.01). CONCLUSION: Opening the mitochondrial permeability transition
      pores may be the basis of the apoptosis of steatotic hepatocytes in vitro, and it
      also may be related to the steatosis of NAFLD in human beings.

PMID- 18073068
TI  - [Molecular mechanism of ciglitazone inhibiting the expression of extracellular
      matrix in human hepatic stellate cells].
AB  - OBJECTIVE: We tested a hypothesis that PPARgamma inhibits TGFbeta1-activation of
      TGFbeta receptor (TGFbetaR)-1 signaling in quiescent stellate cells, thereby
      abrogating Smad3 phosphorylation and inhibiting PAI-1 and collagen expressions.
      METHODS: Human stellate cells (HSC) were cultured in a medium containing
      isobutylmethylxanthine, dexamethasone and insulin (MDI) to induce a quiescent
      adipocytic phenotype one, and then they were treated with TGFbeta1 with or
      without SB431542, a TGFbetaR1 kinase inhibitor, or the PPARgamma agonist
      ciglitazone. Effects on Smad 3 phosphorylation, TGFbeta-responsive
      transcriptional activity, and expressions of collagen and PAI-1 were assessed.
      RESULTS: Culturing HSC in MDI induced an adipocytic phenotype characterized by
      lipid accumulation and increased PPARgamma expression and transcriptional
      activity. TGFbeta1 treatment caused dose- and time-dependent increases in ECM
      gene expression, increasing collagen and PAI-1 mRNAs by 3 fold within 3 h and
      increasing PAI-1 protein levels by 8 fold within 6 h. Treatment with the
      TGFbetaR1 kinase inhibitor, SB431542, inhibited all of these responses. The
      PPARbeta agonist ciglitazone also caused a dose-dependent inhibition of
      TGFbeta1's fibrogenic actions. 1 mmol/L ciglitazone blocked TGFbeta1
      transcriptional activity and abolished TGFbeta-mediated induction of collagen and
      PAI-1 expressions. CONCLUSION: The anti-fibrotic ability of PPARgamma agonist
      ciglitazone may be related to its ability to inhibit TGFbeta1-TGFbetaR1 signaling
      and blocking pSmad3-dependent induction of PAI-1 and collagen expression.

PMID- 18073069
TI  - [Mechanisms of the actions of interferons].

PMID- 18073070
TI  - [Interferons and chronic hepatitis C treatment].

PMID- 18073071
TI  - [Interferons for treating chronic hepatitis B].

PMID- 18073072
TI  - [The value of interferon-a in the management of hepatocellular carcinoma].

PMID- 18073073
TI  - [Detection of titers and replications of HBV DNA in peripheral blood mononuclear
      cells and bone marrow CD34+ cells in liver transplant recipients receiving
      prophylactic combined lamivudine and hepatitis B immunoglobulin treatments].

PMID- 18073074
TI  - [Effect and mechanism of reduced glutathione treatment on liver functional
      impairments in experimental severe acute pancreatitis in rats].

PMID- 18073075
TI  - [Treatment of hepatic cysts with percutaneous injections of acetic acid].

PMID- 18073076
TI  - [OKT3 for recipients with steroid-resistant acute rejection after liver
      transplantation].

PMID- 18073077
TI  - [Expression of PPAR-gamma in rat liver fibrosis and the effect of Dan-shao-hua
      xian capsule on its expression pattern].

PMID- 18073078
TI  - [17beta-estradiol inhibits the development of rat liver fibrosis by enhancing
      expression of hepatocyte growth factor].

PMID- 18073079
TI  - [Correlations between intrahepatic CD4+, CD8+, and virus-specific CD8+ T cells
      and liver injury in chronic severe hepatitis].

PMID- 18073080
TI  - [Effect of TIMP-1 siRNA on liver fibrosis in rats under ultrasound microbubble
      and ultrasound irradiation].

PMID- 18073081
TI  - [Preparation and characterization of a murine monoclonal antibody against human
      ALDH1A1].

PMID- 18073082
TI  - [Effects of rhein on nonalcoholic steatohepatitis in rats].

PMID- 18073083
TI  - [Dynamic characteristics of PDGF-C during liver lipoid degeneration and
      fibrogenesis processes in rats].

PMID- 18073084
TI  - [Effects of Chinese herb compound hanfangji on rat liver fibrosis].

PMID- 18073085
TI  - [A case report of successful reestablishment of immunity to HBV after liver
      transplantation].

PMID- 18073086
TI  - [Report of an international workshop: roadmap for management of patients
      receiving oral therapy for chronic hepatitis B].

PMID- 18073087
TI  - [Progress in the study of proteasome inhibitor inducing hepatic stellate cell
      apoptosis].

PMID- 18073089
TI  - Descriptive spatial epidemiology of subclinical Salmonella infection in finisher
      pig herds: application of a novel method of spatially adaptive smoothing.
AB  - We describe the spatial epidemiological features of the 6.8 million meat-juice
      serological tests that were conducted between 1995 and 2004 as part of the Danish
      swine Salmonella control programme. We investigated pig and farm density using
      edge-corrected kernel estimations. Pigs were aggregated at the county level to
      assess county-level risk, and then we investigated farm-level risk by giving
      farms a case or non-case label using a cut-off of 40% of pigs positive.
      Conditional probability surfaces, correcting for the underlying population at
      risk, were produced for each year of the study period using a novel kernel
      estimator with a spatially adaptive smoothing bandwidth. This approach improves
      on previous methods by allowing focussed estimation of risk in areas of high
      population density while maintaining stable estimates in regions where the data
      are sparse. Two spatial trends in the conditional probability of a farm being a
      case were evident: (1) over the whole country, with the highest risk in the west
      compared to the east; and (2) on the Jutland peninsula with the highest risk in
      the north and south. At the farm-level a consistent area of risk was the south
      west of Jutland. Case farms tended to aggregate indicating spatial dependency in
      the data. We found no association between pig or farm density and Salmonella
      risk. We generated hypotheses for this spatial pattern of risk and we conclude
      that this spatial pattern should be considered in the development of surveillance
      strategies and as a basis for further, more detailed analyses of the data.

PMID- 18073088
TI  - Foodborne zoonoses due to meat: a quantitative approach for a comparative risk
      assessment applied to pig slaughtering in Europe.
AB  - Foodborne zoonoses have a major health impact in industrialised countries. New
      European food safety regulations were issued to apply risk analysis to the food
      chain. The severity of foodborne zoonoses and the exposure of humans to
      biological hazards transmitted by food must be assessed. For meat, inspection at
      the slaughterhouse is historically the main means of control to protect
      consumers. However, the levels of detection of biological hazards during meat
      inspection have not been established in quantitative terms yet. Pork is the most
      frequently consumed meat in Europe. The aim of this study was to provide elements
      for quantifying levels of risk for pork consumers and lack of detection by meat
      inspection. Information concerning hazard identification and characterisation was
      obtained by the compilation and statistical analysis of data from 440 literature
      references. The incidence and severity of human cases due to pork consumption in
      Europe were assessed in order to calculate risk scores. A ratio of non-control
      was calculated for each biological hazard identified as currently established in
      Europe, i.e. the incidence of human cases divided by the prevalence of hazards on
      pork. Salmonella enterica, Yersinia enterocolitica and Campylobacter spp. were
      characterised by high incidence rates. Listeria monocytogenes, Clostridium
      botulinum and Mycobacterium spp. showed the highest severity scores. The three
      main high risk hazards involved in foodborne infections, Y. enterocolitica, S.
      enterica and Campylobacter spp. are characterised by high non-control ratios and
      cannot be detected by macroscopic examination of carcasses. New means of hazard
      control are needed to complement the classical macroscopic examination.

PMID- 18073090
TI  - Farm practices to control E. coli O157 in young cattle--a randomised controlled
      trial.
AB  - A randomised controlled trial was used to investigate the effect of three complex
      management intervention packages to reduce the burden of E. coli O157 in groups
      of young-stock on cattle farms in England and Wales. All intervention farms were
      assigned measures to avoid buying in new animals and having direct contact or
      sharing water sources with other cattle. Furthermore, package A (7 farms) aimed
      to keep a clean environment and closed groups of young-stock; package B (14
      farms) aimed for improved water and feed hygiene, whilst package C was assigned
      both A and B. The control farms (26 farms) were asked not to alter their
      practices. Farms, which were assigned intervention package A, exhibited a 48%
      reduction in E. coli O157 burden over the 4.5 months (average) of observation,
      compared to 18% on the control farms. The effect of package A compared to the
      control farms in a crude intention-to-treat model was RR = 0.26 (p=0.122). When
      the risk ratio was adjusted for actual application of the different measures, the
      effect of intervention package A became stronger and statistically significant
      (RR = 0.14 p=0.032). Statistical evidence (p< 0.05) showed that dry bedding and
      maintaining animals in the same groups were the most important measures within
      the package and weak evidence (p< 0.1) showed that a closed herd policy and no
      contact with other cattle may also be of importance. Compliance with the other
      measures in package A had no influence on the effect of the package. No evidence
      of effect of the other two intervention packages was found.

PMID- 18073091
TI  - Examination of animal and zoonotic pathogens using microarrays.
AB  - The advancement in functional genomics, such as DNA microarrays along with the
      genome availability of important pathogens as well as of human and livestock
      species has allowed scientists to study the expression of thousands of genes in a
      single step. In the past decade, DNA arrays have been employed to study
      infectious processes of pathogens, in diagnostics, and to study host-pathogen
      interactions. The generation of enormous data sets by microarray experiments also
      stimulated the growth of a new generation of analytical software. The information
      provided by microarray experiments has been useful in generating new hypotheses
      for future research. The concept of DNA array technology has been utilized in the
      development of novel diagnostic methods. This review highlights the application
      of microarrays in the field of veterinary research.

PMID- 18073092
TI  - The toll-like receptor-4 (TLR-4) pathway and its possible role in the
      pathogenesis of Escherichia coli mastitis in dairy cattle.
AB  - Mastitis is one of the most costly production diseases in the dairy industry that
      is caused by a wide array of microorganisms. In this review, we focus on the Gram
      negative Escherichia coli infections that often occur at periods when the innate
      immune defence mechanisms are impaired (i.e., parturition through the first 60
      days of lactation). There is substantial evidence demonstrating that at these
      periods, the expected influx of polymorphonuclear neutrophil leukocytes (PMN)
      into the mammary gland is delayed during inflammation after intramammary
      infection with E. coli. Here, we provide some hypotheses on the potential
      mechanisms of action on how the disease may develop under circumstances of
      immunosuppression, and describe the potential involvement of the toll-like
      receptor-4 signal transduction pathway in the pathogenesis of E. coli mastitis.
      In addition, some ideas are proposed to help prevent E. coli mastitis and
      potentially other diseases caused by Gram-negative infections in general.

PMID- 18073093
TI  - Bovine IgG1 antibodies against Mycobacterium avium subsp. paratuberculosis
      protein p34-cx improve association of bacteria and macrophages.
AB  - Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (Map), is
      a chronic granulomatous enteric disease in cattle. Among molecular components of
      Map, protein p34 was identified as specific and immunodominant for bovine B
      cells. In order to determine if specific antibodies could influence the course of
      Map pathogenesis, the interaction between bacteria and bovine macrophages was
      studied. Bovine polyclonal antibodies from 3 calves vaccinated with protein p34
      cx, 6 calves vaccinated with heat-killed Map, 8 naturally infected, and 3 healthy
      calves -as negative controls- were used. Specific anti-Map, -p34-cx and -PPA-3
      antibodies were evaluated and isotype characterized. Infected and Map vaccinated
      animals showed similar IgG1 and IgG2 response against Map whole bacteria. When
      p34-cx was used as the antigen, mainly IgG1 and IgG3 were detected in infected
      and only IgG1 in p34-cx vaccinated animals. Bovine polyclonal antibodies from
      three animals of each category were isolated and affinity purified through Map
      and p34-cx columns. The effect of these antibodies in association with Map and a
      transformed bovine peritoneal macrophage's cell line (Bov-Mac) as well as
      activation of NF-kappaB transcription factor was studied. Our results show that
      association of Map significantly increased in vitro after pretreatment with
      bovine anti-Map or anti-p34-cx antibodies obtained from vaccinated or infected
      cattle when compared with those of controls. Improved activation of NF-kappaB was
      detected in macrophages that ingested Map opsonized with either anti-Map or anti
      p34-cx specific antibodies of infected or vaccinated calves, suggesting that both
      anti-Map and IgG1 anti-p34-cx antibodies support Map-macrophage interactions.

PMID- 18073094
TI  - Classical swine fever virus induces activation of plasmacytoid and conventional
      dendritic cells in tonsil, blood, and spleen of infected pigs.
AB  - Classical swine fever virus (CSFV) compromises the host immune system, causing
      indirect leucopoenia and disruption of in vitro T cell stimulation capacity. In
      order to explore the potential role of dendritic cells (DC) in such phenomena,
      the activation of conventional DC (cDC) and plasmacytoid DC (pDC) in blood and
      secondary lymphoid organs of infected pigs was investigated in the early time
      course post-inoculation (pi), together with viral components dissemination and
      cytokine production in serum. Whereas CD11R1+CD172a+ cDC frequencies were
      markedly reduced in blood and spleen, analysis of CD4+CD172a+ pDC numbers
      revealed a rapid turn-over of this DC subset in tissues pi. Both subsets matured
      and were activated after infection, as demonstrated by down-regulation of CD1a,
      up-regulation of the co-stimulation molecule CD80/86 and expression of cytokines.
      cDC essentially expressed tumor necrosis factor alpha (TNF-alpha) and interleukin
      (IL)-10, whereas pDC produced alpha interferon (IFN-alpha) and IL-12. IFN-alpha
      and TNF-alpha productions revealed an enhancement of innate anti-viral immune
      responses. Detection of antigen activated B lymphocytes in tonsil T-cell areas at
      72 h pi, subsequently to the transient translocation of the viral E2 protein
      within germinal centres at 48 h pi, indicates the initiation of humoral response.
      This response was also evidenced by an important IL-10 production in serum one
      week pi. IL-12 expression in organs, as well as transient detection of IL-18 and
      IFN-gamma in serum, reflected the initiation of cellular immune responses.
      However, the uncommonly high levels of TNF-alpha and IFN-alpha produced by DC and
      measured in serum early post-infection, together with IL-10 expression in spleen,
      could play a role in the disruption of immune system cells, either inducing
      apoptosis or impairing DC functionalities themselves.

PMID- 18073095
TI  - Analysis of cellular responses to Mycoplasma mycoides subsp. mycoides small
      colony biotype associated with control of contagious bovine pleuropneumonia.
AB  - A better understanding of protective immune memory against contagious bovine
      pleuropneumonia (CBPP) is needed in order to facilitate the development of safer
      vaccines based on selected components of the pathogen. For this purpose, cells
      collected from lymph nodes draining the lungs of Mycoplasma mycoides subsp.
      mycoides small colony biotype (MmmSC)-infected cattle were stimulated with the
      pathogen in vitro and evaluated concurrently for proliferation (CFSE based
      method), expression of activation, memory markers and cytokine production. Direct
      evidence is presented for a major contribution of CD4+ T cells to the vigorous
      proliferative and T1 biased cytokine recall responses observed in cattle that
      have recovered from infection but not in animals developing the acute form of the
      disease. Two different phenotypes of MmmSC-specific memory CD4 were observed
      based on CD62L expression and proliferative capacities. Furthermore, recall
      proliferation of B cells also occurred but was strictly dependent on the presence
      of CD4. The information provided in this study will facilitate the search for
      MmmSC antigens that have potential for the development of subunit vaccines
      against CBPP.

PMID- 18073096
TI  - Physiological role of the cellular prion protein.
AB  - The prion protein (PrP) plays a key role in the pathogenesis of prion diseases.
      However, the normal function of the protein remains unclear. The cellular isoform
      (PrP(C)) is expressed most abundantly in the brain, but has also been detected in
      other non-neuronal tissues as diverse as lymphoid cells, lung, heart, kidney,
      gastrointestinal tract, muscle, and mammary glands. Cell biological studies of
      PrP contribute to our understanding of PrP(C) function. Like other membrane
      proteins, PrP(C) is post-translationally processed in the endoplasmic reticulum
      and Golgi on its way to the cell surface after synthesis. Cell surface PrP(C)
      constitutively cycles between the plasma membrane and early endosomes via a
      clathrin-dependent mechanism, a pathway consistent with a suggested role for
      PrP(C) in cellular trafficking of copper ions. Although PrP(-/-) mice have been
      reported to have only minor alterations in immune function, PrP(C) is up
      regulated in T cell activation and may be expressed at higher levels by
      specialized classes of lymphocytes. Furthermore, antibody cross-linking of
      surface PrP(C) modulates T cell activation and leads to rearrangements of lipid
      raft constituents and increased phosphorylation of signaling proteins. These
      findings appear to indicate an important but, as yet, ill-defined role in T cell
      function. Recent work has suggested that PrP(C) is required for self-renewal of
      haematopoietic stem cells. PrP(C) is highly expressed in the central nervous
      system, and since this is the major site of prion pathology, most interest has
      focused on defining the role of PrP(C) in neurones. Although PrP(-/-) mice have a
      grossly normal neurological phenotype, even when neuronal PrP(C) is knocked out
      postnatally, they do have subtle abnormalities in synaptic transmission,
      hippocampal morphology, circadian rhythms, and cognition and seizure threshold.
      Other postulated neuronal roles for PrP(C) include copper-binding, as an anti-
      and conversely, pro-apoptotic protein, as a signaling molecule, and in supporting
      neuronal morphology and adhesion. The prion protein may also function as a metal
      binding protein such as copper, yielding cellular antioxidant capacity suggesting
      a role in the oxidative stress homeostasis. Finally, recent observations on the
      role of PrP(C) in long-term memory open a challenging field.

PMID- 18073097
TI  - Cell models of prion infection.
AB  - Due to recent renewal of interest and concerns in prion diseases, a number of
      cell systems permissive to prion multiplication have been generated in the last
      years. These include established cell lines, neuronal stem cells and primary
      neuronal cultures. While most of these models are permissive to experimental,
      mouse-adapted strains of prions, the propagation of natural field isolates from
      sheep scrapie and chronic wasting disease has been recently achieved. These
      models have improved our knowledge on the molecular and cellular events
      controlling the conversion of the PrP(C) protein into abnormal isoforms and on
      the cell-to-cell spreading of prions. Infected cultured cells will also
      facilitate investigations on the molecular basis of strain identity and on the
      mechanisms that lead to neurodegeneration. The ongoing development of new cell
      models with improved characteristics will certainly be useful for a number of
      unanswered critical issues in the prion field.

PMID- 18073098
TI  - Generation of protein structures for the 21(st) century.

PMID- 18073099
TI  - Update on the protein structure initiative.

PMID- 18073100
TI  - Collecting butterflies and the protein structure initiative: the right questions?

PMID- 18073101
TI  - A future for the protein structure initiative.

PMID- 18073102
TI  - Some ill considered comments on the protein structure initiative.

PMID- 18073103
TI  - Impact of structures from the protein structure initiative.

PMID- 18073104
TI  - Observation of decreased radiation damage at higher dose rates in room
      temperature protein crystallography.
AB  - Radiation damage can be a problem when utilizing ionizing X-radiation in
      macromolecular crystallography. The dose dependence of radiation damage to eight
      lysozyme crystals at room temperature (292 K) was investigated in order to
      provide an accurate comparison with cryotemperature (100 K) results and to allow
      researchers to calculate expected maximum room-temperature-crystal lifetimes
      prior to data collection. Results of intensity-loss analysis unexpectedly showed
      that the dose tolerated by a crystal is dependent on the dose rate according to a
      positive linear relationship (99% correlation coefficient); a 60% increase in
      dose rate gave a 4-fold increase in crystal lifetime over the range studied.
      Alternative metrics of damage were also assessed from room temperature data. In
      the dose-rate range tested (6 Gy s(-1) to 10 Gy s(-1)), data collection at 100 K
      appears to offer a 26-113 times increase in the lifetime of the crystal.

PMID- 18073105
TI  - Feast/famine regulation by transcription factor FL11 for the survival of the
      hyperthermophilic archaeon Pyrococcus OT3.
AB  - Transcriptional repressor FL11 from the hyperthermophilic archaeon, Pyrococcus
      OT3, was crystallized in its dimer form in complex with a DNA duplex,
      TGAAAWWWTTTCA. Chemical contacting of FL11 to the terminal 5 bps, and DNA bending
      by propeller twisting at WWW confirmed specificity of the interaction. Dimer
      binding sites were identified in promoters of approximately 200 transcription
      units coding, for example, H+-ATPase and NAD(P)H dehydrogenase. In the presence
      of lysine, four FL11 dimers were shown to assemble into an octamer, thereby
      covering the fl11 promoter. In the "feast" mode, when P. OT3 grows on amino
      acids, the FL11 octamer will terminate transcription of fl11, as was shown in
      vitro, thereby derepressing transcription of many metabolic genes. In the
      "famine" mode in the absence of lysine, approximately 6000 FL11 dimers present
      per cell will arrest growth. This regulation resembles global regulation by
      Escherichia coli leucine-responsive regulatory protein, and hints at a prototype
      of transcription regulations now highly diverged.

PMID- 18073106
TI  - Quaternary structure change as a mechanism for the regulation of thymidine kinase
      1-like enzymes.
AB  - The human cytosolic thymidine kinase (TK) and structurally related TKs in
      prokaryotes play a crucial role in the synthesis and regulation of the cellular
      thymidine triphosphate pool. We report the crystal structures of the TK
      homotetramer from Thermotoga maritima in four different states: its apo-form, a
      binary complex with thymidine, as well as the ternary structures with the two
      substrates (thymidine/AppNHp) and the reaction products (TMP/ADP). In combination
      with fluorescence spectroscopy and mutagenesis experiments, our results
      demonstrate that ATP binding is linked to a substantial reorganization of the
      enzyme quaternary structure, leading to a transition from a closed, inactive
      conformation to an open, catalytic state. We hypothesize that these structural
      changes are relevant to enzyme function in situ as part of the catalytic cycle
      and serve an important role in regulating enzyme activity by amplifying the
      effects of feedback inhibitor binding.

PMID- 18073107
TI  - Modeling backbone flexibility improves protein stability estimation.
AB  - In designing mutagenesis experiments, it is often crucial to know how certain
      mutations will affect the structure and thermodynamic stability of the protein.
      Here, we present a methodology, Eris, to efficiently and accurately compute the
      stability changes of proteins upon mutations using our protein-modeling suite,
      Medusa. We evaluate the stability changes upon mutations for 595 mutants from
      five structurally unrelated proteins, and find significant correlations between
      the predicted and experimental results. For cases when the high-resolution
      protein structure is not available, we find that better predictions are obtained
      by backbone structure prerelaxation. The advantage of our approach is that it is
      based on physical descriptions of atomic interactions, and does not rely on
      parameter training with available experimental protein stability data. Unlike
      other methods, Eris also models the backbone flexibility, thereby allowing for
      determination of the mutation-induced backbone conformational changes. Eris is
      freely available via the web server at http://eris.dokhlab.org.

PMID- 18073108
TI  - A CTP-dependent archaeal riboflavin kinase forms a bridge in the evolution of
      cradle-loop barrels.
AB  - Proteins of the cradle-loop barrel metafold are formed by duplication of a
      conserved betaalphabeta-element, suggesting a common evolutionary origin from an
      ancestral group of nucleic acid-binding proteins. The basal fold within this
      metafold, the RIFT barrel, is also found in a wide range of enzymes, whose
      homologous relationship with the nucleic acid-binding group is unclear. We have
      characterized a protein family that is intermediate in sequence and structure
      between the basal group of cradle-loop barrels and one family of RIFT-barrel
      enzymes, the riboflavin kinases. We report the structure, substrate-binding mode,
      and catalytic activity for one of these proteins, Methanocaldococcus jannaschii
      Mj0056, which is an archaeal riboflavin kinase. Mj0056 is unusual in utilizing
      CTP rather than ATP as the donor nucleotide, and sequence conservation in the
      relevant residues suggests that this is a general feature of archaeal riboflavin
      kinases.

PMID- 18073109
TI  - Phosphorylation-induced conformational switching of CPI-17 produces a potent
      myosin phosphatase inhibitor.
AB  - Phosphorylation of endogenous inhibitor proteins for type-1 Ser/Thr phosphatase
      (PP1) provides a mechanism for reciprocal coordination of kinase and phosphatase
      activities. A myosin phosphatase inhibitor protein CPI-17 is phosphorylated at
      Thr38 through G-protein-mediated signals, resulting in a >1000-fold increase in
      inhibitory potency. We show here the solution NMR structure of phospho-T38-CPI-17
      with rmsd of 0.36 +/- 0.06 A for the backbone secondary structure, which reveals
      how phosphorylation triggers a conformational change and exposes an inhibitory
      surface. This active conformation is stabilized by the formation of a hydrophobic
      core of intercalated side chains, which is not formed in a phospho-mimetic D38
      form of CPI-17. Thus, the profound increase in potency of CPI-17 arises from
      phosphorylation, conformational change, and hydrophobic stabilization of a rigid
      structure that poses the phosphorylated residue on the protein surface and
      restricts its hydrolysis by myosin phosphatase. Our results provide structural
      insights into transduction of kinase signals by PP1 inhibitor proteins.

PMID- 18073110
TI  - The NMDA receptor NR1 C1 region bound to calmodulin: structural insights into
      functional differences between homologous domains.
AB  - Calmodulin (CaM) regulates tetrameric N-methyl-D-aspartate receptors (NMDARs) by
      binding tightly to the C0 and C1 regions of its NR1 subunit. A crystal structure
      (2HQW; 1.96 A) of calcium-saturated CaM bound to NR1C1 (peptide spanning 875-898)
      showed that NR1 S890, whose phosphorylation regulates membrane localization, was
      solvent protected, whereas the endoplasmic reticulum retention motif was solvent
      exposed. NR1 F880 filled the CaM C-domain pocket, whereas T886 was closest to the
      N-domain pocket. This 1-7 pattern was most similar to that in the CaM-MARCKS
      complex. Comparison of CaM-ligand wrap-around conformations identified a core
      tetrad of CaM C-domain residues (FLMM(C)) that contacted all ligands
      consistently. An identical tetrad of N-domain residues (FLMM(N)) made variable
      sets of contacts with ligands. This CaM-NR1C1 structure provides a foundation for
      designing mutants to test the role of CaM in NR1 trafficking as well as insights
      into how the homologous CaM domains have different roles in molecular
      recognition.

PMID- 18073112
TI  - Combining efficient conformational sampling with a deformable elastic network
      model facilitates structure refinement at low resolution.
AB  - Structural studies of large proteins and protein assemblies are a difficult and
      pressing challenge in molecular biology. Experiments often yield only low
      resolution or sparse data that are not sufficient to fully determine atomistic
      structures. We have developed a general geometry-based algorithm that efficiently
      samples conformational space under constraints imposed by low-resolution density
      maps obtained from electron microscopy or X-ray crystallography experiments. A
      deformable elastic network (DEN) is used to restrain the sampling to prior
      knowledge of an approximate structure. The DEN restraints dramatically reduce
      over-fitting, especially at low resolution. Cross-validation is used to optimally
      weight the structural information and experimental data. Our algorithm is robust
      even for noise-added density maps and has a large radius of convergence for our
      test case. The DEN restraints can also be used to enhance reciprocal space
      simulated annealing refinement.

PMID- 18073111
TI  - Transformation efficiency of RasQ61 mutants linked to structural features of the
      switch regions in the presence of Raf.
AB  - Transformation efficiencies of Ras mutants at residue 61 range over three orders
      of magnitude, but the in vitro GTPase activity decreases 10-fold for all mutants.
      We show that Raf impairs the GTPase activity of RasQ61L, suggesting that the
      Ras/Raf complex differentially modulates transformation. Our crystal structures
      show that, in transforming mutants, switch II takes part in a network of
      hydrophobic interactions burying the nucleotide and precatalytic water molecule.
      Our results suggest that Y32 and a water molecule bridging it to the gamma
      phosphate in the wild-type structure play a role in GTP hydrolysis in lieu of the
      Arg finger in the absence of GAP. The bridging water molecule is absent in the
      transforming mutants, contributing to the burying of the nucleotide. We propose a
      mechanism for intrinsic hydrolysis in Raf-bound Ras and elucidate structural
      features in the Q61 mutants that correlate with their potency to transform cells.

PMID- 18073113
TI  - Structural basis of the initial binding of tRNA(Ile) lysidine synthetase TilS
      with ATP and L-lysine.
AB  - In the bacterial genetic-code system, the codon AUA is decoded as isoleucine by
      tRNA(Ile)(2) with the lysidine residue at the wobble position. Lysidine is
      derived from cytidine, with ATP and L-lysine, by tRNA(Ile) lysidine synthetase
      (TilS), which is an N-type ATP pyrophosphatase. In this study, we determined the
      crystal structure of Aquifex aeolicus TilS, complexed with ATP, Mg2+, and L
      lysine, at 2.5 A resolution. The presence of the TilS-specific subdomain causes
      the active site to have two separate gateways, a large hole and a narrow tunnel
      on the opposite side. ATP is bound inside the hole, and L-lysine is bound at the
      entrance of the tunnel. The conserved Asp36 in the PP-motif coordinates Mg2+. In
      these initial binding modes, the ATP, Mg2+, and L-lysine are held far apart from
      each other, but they seem to be brought together for the reaction upon cytidine
      binding, with putative structural changes of the complex.

PMID- 18073114
TI  - Open-state conformation of the KcsA K+ channel: Monte Carlo normal mode following
      simulations.
AB  - Potassium channels fluctuate between closed and open states. The detailed
      mechanism of the conformational changes opening the intracellular pore in the K+
      channel from Streptomyces lividans (KcsA) is unknown. Applying Monte Carlo normal
      mode following, we find that gating involves rotation and unwinding of the TM2
      bundle, lateral movement of the TM2 helices away from the channel axis, and
      disappearance of the TM2 bundle. The open-state conformation of KcsA exhibits a
      very wide inner vestibule, with a radius approximately 5-7 A and inner helices
      bent at the A98-G99 hinge. Computed conformational changes demonstrate that spin
      labeling and X-ray experiments illuminate different stages in gating: transition
      begins with clockwise rotation of the TM2 helices ending at a final state with
      the TM2 bend hinged near residues A98-G99. The concordance between the
      computational and experimental results provides atomic-level insights into the
      structural rearrangements of the channel's inner pore.

PMID- 18073115
TI  - Crystal structure of AcrB in complex with a single transmembrane subunit reveals
      another twist.
AB  - Bacterial drug resistance is a serious concern for human health. Multidrug efflux
      pumps export a broad variety of substrates out of the cell and thereby convey
      resistance to the host. In Escherichia coli, the AcrB:AcrA:TolC efflux complex
      forms a principal transporter for which structures of the individual component
      proteins have been determined in isolation. Here, we present the X-ray structure
      of AcrB in complex with a single transmembrane protein, assigned by mass
      spectrometry as YajC. A specific rotation of the periplasmic porter domain of
      AcrB is also revealed, consistent with the hypothesized "twist-to-open" mechanism
      for TolC activation. Growth experiments with yajc-deleted E. coli reveal a modest
      increase in the organism's susceptibility to beta-lactam antibiotics, but this
      effect could not conclusively be attributed to the loss of interactions between
      YajC and AcrB.

PMID- 18073116
TI  - Structural basis for the PufX-mediated dimerization of bacterial photosynthetic
      core complexes.
AB  - In Rhodobacter (Rba.) sphaeroides, the subunit PufX is involved in the dimeric
      organization of the core complex. Here, we report the 3D reconstruction at 12 A
      by cryoelectron microscopy of the core complex of Rba. veldkampii, a complex of
      approximately 300 kDa without symmetry. The core complex is monomeric and
      constituted by a light-harvesting complex 1 (LH1) ring surrounding a uniquely
      oriented reaction center (RC). The LH1 consists of 15 resolved alpha/beta
      heterodimers and is interrupted. Within the opening, PufX polypeptide is assigned
      at a position facing the Q(B) site of the RC. This core complex is different from
      a dissociated dimer of the core complex of Rba. sphaeroides revealing that PufX
      in Rba. veldkampii is unable to dimerize. The absence in PufX of Rba. veldkampii
      of a G(31)XXXG(35) dimerization motif highlights the transmembrane interactions
      between PufX subunits involved in the dimerization of the core complexes of
      Rhodobacter species.

PMID- 18073119
TI  - Epithelium dysfunction in asthma.
AB  - Although asthma is an inflammatory disorder of the conducting airways involving
      T(H)2-type T cells, there is increasing evidence for an important role played by
      the epithelium in orchestrating the inflammatory response by interacting with
      multiple environmental factors to produce a chronic wound scenario involving
      tissue injury and aberrant repair. Part of this abnormal response is the
      consequence of impaired barrier function caused by a primary disruption of
      epithelial tight junctions that allows inhaled substances to pass more easily
      into the airway wall to interact with immune and inflammatory cells. Aberrant
      communication between the damaged and stressed epithelium leads to the generation
      of growth factors that interact with the underlying mesenchyme to promote airway
      remodeling responses and a more chronic and persistent inflammatory phenotype.
      Disordered epithelial function with reduced antioxidant defense and impaired
      capacity to produce primary IFNs may also account for asthmatic susceptibility to
      air pollution and respiratory virus infection, respectively. Considering asthma
      as a disease of impaired barrier function opens new opportunities for therapeutic
      intervention or prevention by agents that could increase the airways resistance
      to the inhaled environment rather than suppressing the immune or inflammatory
      response.

PMID- 18073117
TI  - Assembling NMR structures for the intracellular loops of the human thromboxane A2
      receptor: implication of the G protein-coupling pocket.
AB  - It has been reported that the multiple intracellular loops (iLPs) of the
      thromboxane A(2) receptor (TP) are involved in the receptor G protein coupling.
      In this study, a high-resolution 2D NMR technique was used to determine the 3D
      structures of the first, second, and third iLPs of the TP using synthetic
      peptides constrained into the loop structures. 2D (1)H NMR spectra, TOCSY and
      NOESY were obtained for the two peptides from proton NMR experiments. The NMR
      data was processed and assigned through the Felix 2000 program. Standard methods
      were used to acquire sequence-specific assignments. Structure calculations were
      processed through DGII and NMR refinement programs within the Insight II program.
      We were able to calculate and use the NOE constraints to obtain the superimposed
      structure of 10 structures for each iLP peptide. The NMR-determined structures of
      the iLP peptides were used to refine a homology model of the TP. A 3D G-protein
      binding cavity, formed by the three intracellular loops, was predicted by the
      docking of the C-terminal domain of the Galphaq. Based on the structural model
      and the previous mutagenesis studies, the residues, R130, R60, C223, F138, L360,
      V361, E358 and Y359, which are important for interaction with the G protein, were
      further highlighted. These results reveal the possibly important molecular
      mechanisms in TP signaling and provide structural information to characterize
      other prostanoid receptor signalings.

PMID- 18073120
TI  - Glucocorticoid actions on airway epithelial responses in immunity: functional
      outcomes and molecular targets.
AB  - Research on the biology of airway epithelium in the last decades has
      progressively uncovered the many roles of this cell type during the immune
      response. Far from the early view of the epithelial layer simply as a passive
      barrier, the airway epithelium is now considered a central player in mucosal
      immunity, providing innate mechanisms of first-line host defense as well as
      facilitating adaptive immune responses. Alterations of the epithelial phenotype
      are primarily involved in the pathogenesis of allergic airways disease,
      particularly in severe asthma. Appreciation of the epithelium as target of
      glucocorticoid therapy has also grown, because of studies defining the pathways
      and mediators affected by glucocorticoids, and studies illustrating the relevance
      of the control of the response from epithelium in the overall efficacy of topical
      and systemic therapy with glucocorticoids. Studies of the mechanism of action of
      glucocorticoids within the biology of the immune response of the epithelium have
      uncovered mechanisms of gene regulation involving both transcriptional and
      posttranscriptional events. The view of epithelium as therapeutic target
      therefore has plenty of room to evolve, as new knowledge on the role of
      epithelium in immunity is established and novel pathways mediating glucocorticoid
      regulation are elucidated.

PMID- 18073121
TI  - Gene-environment interaction in allergic disease: more questions, more answers?

PMID- 18073122
TI  - Time for a paradigm shift in asthma treatment: from relieving bronchospasm to
      controlling systemic inflammation.
AB  - Inflammation is a key pathology in asthma. In the central airways local
      inflammation leads to irreversible remodeling and airway dysfunction. Complex
      inflammatory changes also occur in the nose, sinuses, and small airways. In
      particular, rhinitis and asthma are linked by a common pathogenic process with
      common inflammatory cells, mediators, and cytokines. Cross-communication between
      the airways and bone marrow through inflammatory mediators in the circulation
      leads to systemic propagation of airway inflammation. Treatment of asthma has
      traditionally focused on relieving bronchospasm with beta(2)-agonists, which do
      not affect inflammation. Treatment of eosinophilic inflammation in the central
      airways with inhaled corticosteroids reduces local inflammation and improves
      pulmonary function but does not improve the systemic manifestations of asthma. If
      asthma is a systemic disease, the underlying systemic pathology should be
      targeted by identifying common disease mediators, mechanisms, or both that are
      triggered only during active disease. Of currently available therapies,
      leukotriene receptor antagonists block the action of cysteinyl leukotrienes and
      thus improve both asthma and rhinitis and other conditions systemically linked
      with asthma. Other potential treatments include receptor-blocking molecules and
      synthesis inhibitors related to eicosanoid inflammation. Treatment of asthma as a
      systemic disease requires clinical trials that evaluate the effects of new
      treatments on both lung function and the wider systemic pathology.

PMID- 18073123
TI  - Clinical manifestations of airway malacia in young children.
AB  - A case of recurrent respiratory distress, wheezing, and "noisy" breathing in a 6
      month-old infant with a normal birth history and chest radiographic evaluation is
      presented. The distinction between primary and secondary tracheomalacia is
      outlined. This report emphasizes the importance of clinical history in the
      evaluation of primary tracheomalacia.

PMID- 18073124
TI  - IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and
      reversibility with glucocorticoids.
AB  - BACKGROUND: Eosinophilic esophagitis (EE) is an emerging worldwide disease that
      mimics gastroesophageal reflux disease. Early studies have established that
      esophageal eosinophilia occurs in association with T(H)2 allergic responses, and
      we recently identified an EE-specific esophageal transcriptome that included
      eotaxin-3. OBJECTIVE: We sought to determine the mechanism by which this T(H)2
      response leads to EE. METHODS: Real-time PCR and microarray analysis were
      performed on RNA extracted from esophageal biopsy specimens and primary
      esophageal epithelial cell cultures stimulated with IL-13 (0-100 ng/mL).
      Transient transfections in esophageal cell lines were performed with plasmids
      containing the luciferase gene driven by eotaxin-3 promoter fragments and
      modified forms of signal transducer and activator of transcription 6. RESULTS:
      The IL-13 mRNA level was markedly increased (16-fold) in esophageal biopsy
      specimens from patients with EE compared with those from healthy individuals.
      Furthermore, IL-13 treatment of primary esophageal epithelial cells was
      sufficient to induce a global-expression transcript profile that remarkably
      overlapped with the EE-specific esophageal transcriptome. In addition, esophageal
      epithelial cells markedly produce eotaxin-3 after IL-13 stimulation through a
      transcriptional mechanism dependent on signal transducer and activator of
      transcription 6. Lastly, increased IL-13 mRNA levels and the EE transcriptome
      were largely reversible with glucocorticoid treatment in vivo. CONCLUSIONS: Taken
      together, we propose that the pathogenesis of EE is mediated by an IL-13
      stimulated keratinocyte-derived transcriptome that is largely reversible with
      corticosteroid treatment. Furthermore, we identify an in vivo IL-13-induced
      transcriptome that has potential utility for target assessment after anti-IL-13
      therapeutics. CLINICAL IMPLICATIONS: IL-13-induced pathways and genes are
      fundamental processes in the cause and manifestations of EE; as such, therapeutic
      agents that interfere with IL-13 might be particularly useful for disease
      treatment.

PMID- 18073125
TI  - Filaggrin mutations confer susceptibility to atopic dermatitis but not to asthma.
AB  - BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) have been
      strongly associated with atopic dermatitis and allergic phenotypes in multiple
      populations. The role of these mutations in the development of asthma is less
      clear, particularly in patients who do not have coincident atopic dermatitis.
      OBJECTIVE: To determine whether FLG mutations are associated with asthma or
      asthma-related intermediate phenotypes. METHODS: We genotyped 2 loss-of-function
      FLG mutations (R501X and 2282del4) in white children (age 5-12 years) with mild
      to moderate asthma in the Childhood Asthma Management Program. We assessed the
      relationship of these mutations to asthma and allergy-related phenotypes in
      children with and without atopic dermatitis using both population-based and
      family-based tests of association. RESULTS: Nearly 1/3 (185/646) of the
      participating children had atopic dermatitis. Although strong associations were
      observed between FLG mutations and atopic dermatitis (odds ratio, 2.4; P = 7.6 x
      10(-5)) and between the mutations and total serum IgE level (P = .009 in the
      atopic dermatitis cohort), no association was noted with either asthma or asthma
      related phenotypes, including FEV(1), FEV(1)/forced vital capacity, and
      methacholine PC(20) (P > .1 for all tests). CONCLUSION: Although FLG loss-of
      function mutations are consistently associated with atopic dermatitis and other
      allergic phenotypes, these mutations do not appear to influence either
      susceptibility to asthma or asthma severity phenotypes. CLINICAL IMPLICATIONS:
      Filaggrin mutations that predispose to atopic dermatitis do not modulate the
      asthma phenotype.

PMID- 18073126
TI  - The natural history of egg allergy.
AB  - BACKGROUND: Egg allergy is very common, affecting 1% to 2% of children. It is
      generally thought that the majority of children with egg allergy develop
      tolerance in early childhood; however, this has not been examined in a large
      cohort with egg allergy. OBJECTIVE: The purpose of the study was to estimate the
      proportion of children with egg allergy who develop egg tolerance and to identify
      predictors of tolerance development. METHODS: Retrospective chart review of
      patients with egg allergy seen in a tertiary referral clinic. Patients were
      considered to have developed egg tolerance if they tolerated concentrated egg.
      RESULTS: Kaplan-Meier analysis predicted resolution in 4% of patients with egg
      allergy by age 4 years, 12% by age 6 years, 37% by age 10 years, and 68% by age
      16 years. Patients with persistent egg allergy had higher egg IgE levels at all
      ages to age 18 years. A patient's highest recorded egg IgE, presence of other
      atopic disease, and presence of other food allergy were significantly related to
      egg allergy persistence. CONCLUSION: A majority of patients with egg allergy will
      develop egg tolerance, although the rate of tolerance development is slower than
      described previously. Egg IgE is predictive of allergy outcome and should be used
      in counseling patients on prognosis. CLINICAL IMPLICATIONS: Most patients with
      egg allergy are likely to develop egg tolerance by late childhood, with the
      exception of patients with an egg IgE greater than 50 kU/L, who are unlikely to
      develop egg tolerance.

PMID- 18073130
TI  - Lysophosphatidic acid (LPA) promotes E-cadherin ectodomain shedding and OVCA429
      cell invasion in an uPA-dependent manner.
AB  - OBJECTIVES: To evaluate the role of LPA in regulating E-cadherin cell surface
      expression, adhesion, and invasion in epithelial ovarian carcinoma (EOC) cells.
      METHODS: E-cadherin mRNA expression in OVCA429 and IOSE-29 cells was evaluated by
      real-time RT-PCR. Immunofluorescence and Western blot analysis were performed to
      determine cell surface expression and shedding of E-cadherin 80-kDa soluble
      fragment by LPA. Kinetics of LPA-induced uPA activity was followed with a
      colorimetric enzymatic assay. Invasion assays were performed in a modified Boyden
      chamber where cells were allowed to migrate to the bottom compartment through a
      porous filter coated with collagen. Additionally we measured the 80-kDa form from
      the ascites of women with stage III/IV EOC. RESULTS: LPA induces E-cadherin
      shedding of a soluble 80-kDa fragment. We found that this process is mediated by
      the uPA proteolytic cascade. High levels of soluble E-cadherin were found in the
      ascites from women with advanced stage EOC. LPA and a soluble recombinant E
      cadherin-Fc chimera promotes invasion of OVCA429 cells. CONCLUSIONS: LPA induces
      shedding of an 80-kDa E-cadherin-soluble fragment in an uPA-dependent manner and
      promotes in vitro invasion. High levels of soluble E-cadherin in malignant
      ascites may also affect ovarian metastasis.

PMID- 18073128
TI  - Motor coordination deficits in mice lacking RGS9.
AB  - RGS9-2 is a striatum-enriched protein that negatively modulates dopamine and
      opioid receptor signaling. We examined the role of RGS9-2 in modulating complex
      behavior. Genetic deletion of RGS9-2 does not lead to global impairments, but
      results in selective abnormalities in certain behavioral domains. RGS9 knockout
      (KO) mice have decreased motor coordination on the accelerating rotarod and
      deficits in working memory as measured in the delayed-match-to-place version of
      the water maze. In contrast, RGS9 KO mice exhibit normal locomotor activity,
      anxiety-like behavior, cue and contextual fear conditioning, startle threshold,
      and pre-pulse inhibition. These studies are the first to describe a role for RGS9
      2 in motor coordination and working memory and implicate RGS9-2 as a potential
      therapeutic target for motor and cognitive dysfunction.

PMID- 18073129
TI  - Stem cell antigen-1 regulates the tempo of muscle repair through effects on
      proliferation of alpha7 integrin-expressing myoblasts.
AB  - Skeletal muscle repair occurs through a programmed series of events including
      myogenic precursor activation, myoblast proliferation, and differentiation into
      new myofibers. We previously identified a role for Stem cell antigen-1 (Sca-1) in
      myoblast proliferation and differentiation in vitro. We demonstrated that
      blocking Sca-1 expression resulted in sustained myoblast cell division. Others
      have since demonstrated that Sca-1-null myoblasts display a similar phenotype
      when cultured ex vivo. To test the importance of Sca-1 during myogenesis in vivo,
      we employed a myonecrotic injury model in Sca-1(-/-) and Sca-1(+/+) mice. Our
      results demonstrate that Sca-1(-/-) myoblasts exhibit a hyperproliferative
      response consisting of prolonged and accelerated cell division in response to
      injury. This leads to delayed myogenic differentiation and muscle repair. These
      data provide the first in vivo evidence for Sca-1 as a regulator of myoblast
      proliferation during muscle regeneration. These studies also suggest that the
      balance between myogenic precursor proliferation and differentiation is critical
      to normal muscle repair.

PMID- 18073131
TI  - Comments on neoadjuvant chemotherapy in cervical cancer.

PMID- 18073132
TI  - Effects of root dentin surface coating with all-in-one adhesive materials on
      biofilm adherence.
AB  - OBJECTIVES: Sealing of exposed root dentinal surfaces with adhesive materials is
      expected to be a promising approach for preventing root dentin caries. The aim of
      this study was to evaluate the effects of surface coating with all-in-one
      adhesives on inhibiting Streptococcus mutans biofilm attachment. MATERIALS AND
      METHODS: Bovine root dentin was cut and ground with #600-grit SiC paper. Each of
      the three all-in-one adhesives, Hybrid Bond (HB), Reactmer Bond (RB) or Shake One
      (SO) was single-coated on the dentin surfaces according to the manufacturers'
      instructions. The dentin surface without coating served as the control. The
      surface roughness of the coated and non-coated dentin surfaces was recorded by
      means of laser microscope measurements. S. mutans artificial biofilms were then
      grown on the surface of each specimen in a microcosm for 20h. The amounts of
      bacteria and water insoluble glucan in the retained biofilm on the surface of the
      specimens were measured. All numerical data were statistically analyzed using one
      way ANOVA & Tukey's HSD (p<0.05). RESULTS: All of the coated groups showed
      significantly lower susceptibility to biofilm attachment compared with the non
      coated root dentin (p<0.05). Among the coated groups, SO showed the lowest
      susceptibility for biofilm formation. CONCLUSIONS: Three all-in-one adhesive
      materials could be effective for root surface coating. A fluoride-releasing
      adhesive, SO demonstrated the strongest potentiality in resisting biofilm
      formation.

PMID- 18073133
TI  - Effects of random subject rotation on optimised diffusion gradient sampling
      schemes in diffusion tensor MRI.
AB  - The choice of the number (N) and orientation of diffusion sampling gradients
      required to measure accurately the water diffusion tensor remains contentious.
      Monte Carlo studies have suggested that between 20 and 30 uniformly distributed
      sampling orientations are required to provide robust estimates of water
      diffusions parameters. These simulations have not, however, taken into account
      what effect random subject motion, specifically rotation, might have on optimised
      gradient schemes, a problem which is especially relevant to clinical diffusion
      tensor MRI (DT-MRI). Here this question is investigated using Monte Carlo
      simulations of icosahedral sampling schemes and in vivo data. These polyhedra
      based schemes, which have the advantage that large N can be created from
      optimised subsets of smaller N, appear to be ideal for the study of restless
      subjects since if scanning needs to be prematurely terminated it should be
      possible to identify a subset of images that have been acquired with a near
      optimised sampling scheme. The simulations and in vivo data show that as N
      increases, the rotational variance of fractional anisotropy (FA) estimates
      becomes progressively less dependent on the magnitude of subject rotation
      (alpha), while higher FA values are progressively underestimated as alpha
      increases. These data indicate that for large subject rotations the B-matrix
      should be recalculated to provide accurate diffusion anisotropy information.

PMID- 18073134
TI  - Ischemia deteriorates the spike encoding of rat cerebellar Purkinje cells by
      raising intracellular Ca2+.
AB  - Ischemia-induced excitotoxicity at cerebellar Purkinje cells is presumably due to
      a persistent glutamate action. To the fact that they are more vulnerable to
      ischemia than other glutamate-innervated neurons, we studied whether additional
      mechanisms are present and whether cytoplasm Ca(2+) plays a key role in their
      ischemic excitotoxicity. Ischemic changes in the excitability of Purkinje cells
      were measured by whole-cell recording in cerebellar slices of rats with less
      glutamate action. The role of cytoplasm Ca(2+) was examined by two-photon
      cellular imaging and BAPTA infusion in Purkinje cells. Lowering perfusion rate to
      cerebellar slices deteriorated spike timing and raised spike capacity of Purkinje
      cells. These changes were associated with the reduction of spike refractory
      periods and threshold potentials, as well as the loss of their control to spike
      encoding. Ischemia-induced functional deterioration at Purkinje neurons was
      accompanied by cytoplasm Ca(2+) rise and prevented by BAPTA infusion. Therefore,
      the ischemia destabilizes the spike encoding of Purkinje cells via raising
      cytoplasm Ca(2+) without a need for glutamate, which subsequently causes their
      excitotoxic death.

PMID- 18073135
TI  - Phosphorylation of focal adhesion kinase promotes extravasation of breast cancer
      cells.
AB  - Inhibition of focal adhesion kinase (FAK) delays transendothelial migration of
      breast cancer cells. Here we investigate whether phosphorylation of specific
      tyrosine residues of FAK (397, 861, and 925) known to control aspects of cell
      migration on extracellular matrix (ECM), are also involved in transendothelial
      migration. AU-565 and MDA-MB-231 cells expressing Phe397 FAK show delayed or
      decreased transendothelial migration, demonstrating the involvement of the FAK
      autophosphorylation site. Only MDA-MB-231 cells expressing Phe861 FAK exhibit
      delayed transendothelial migration. Neither MDA-MB-231 nor AU-565 cells
      expressing Phe925 FAK show a change in transendothelial migration compared to
      untreated cancer cells. These findings suggest that modified signaling mechanisms
      regulate cancer cell migration through an endothelial monolayer versus those
      involved in cell migration on or through ECM.

PMID- 18073136
TI  - Characters of very ancient proteins.
AB  - Tracing the characters of very ancient proteins represents one of the biggest
      challenges in the study of origin of life. Although there are no primitive
      protein fossils remaining, the characters of very ancient proteins can be traced
      by molecular fossils embedded in modern proteins. In this paper, first the prior
      findings in this area are outlined and then a new strategy is proposed to address
      the intriguing issue. It is interesting to find that various molecular fossils
      and different protein datasets lead to similar conclusions on the features of
      very ancient proteins, which can be summarized as follows: (i) the architectures
      of very ancient proteins belong to the following folds: P-loop containing
      nucleoside triphosphate hydrolases (c.37), TIM beta/alpha-barrel (c.1), NAD(P)
      binding Rossmann-fold domains (c.2), Ferredoxin-like (d.58), Flavodoxin-like
      (c.23) and Ribonuclease H-like motif (c.55); (ii) the functions of very ancient
      proteins are related to the metabolisms of purine, pyrimidine, porphyrin,
      chlorophyll and carbohydrates; (iii) a certain part of very ancient proteins need
      cofactors (such as ATP, NADH or NADPH) to work normally.

PMID- 18073137
TI  - Activin A stimulates IgA expression in mouse B cells.
AB  - In this study, a potential role for activin A in mouse immunoglobulin (Ig)
      regulation was investigated. We observed that activin A increased IgA secretion
      in B lymphoma cells. In contrast, little effect was observed on IgM and IgG2b
      secretion. Activin A also significantly increased surface IgA expression and Ig
      germ-line alpha transcript (GLT(alpha)) levels. In parallel, activin A increased
      GLT(alpha) and post-switch transcripts alpha (PST(alpha)) expression in normal B
      cells, which was augmented by IL-5. An increase in IgA production by surface IgA
      negative B cells by activin A was apparent. Finally, the increase of IgA
      secretion by activin A was blocked by an activin receptor inhibitor (SB431542).
      The increase of GLT(alpha) by activin A was augmented by Smad3/4 overexpression
      and abolished by Smad3 dominant negative overexpression. These results suggest
      that activin A induces IgA isotype switching via Smad3/4-mediated germ line alpha
      transcription.

PMID- 18073138
TI  - Adipose expression of catalase is regulated via a novel remote PPARgamma
      responsive region.
AB  - In adipose tissue of obese mice, the expression of catalase, an anti-oxidant
      enzyme, significantly decreases, which may cause insufficient elimination of
      hydrogen peroxide, but it does not in liver or skeletal muscle. However, the
      precise regulatory mechanism of catalase expression in adipocytes has not been
      fully defined. Here, we demonstrated that adipose tissues highly expressed
      catalase on the level comparable to liver and kidney, and treatment of mice with
      PPARgamma agonist significantly enhanced catalase expression in adipose tissue
      but not in liver. In 3T3-L1 cells, mRNA expression of catalase was up-regulated
      by the induction for adipose differentiation, and down-regulated by TNFalpha, in
      parallel with alterations in PPARgamma expression. PPARgamma agonist
      significantly enhanced catalase mRNA and activity. Furthermore, we newly
      identified a remote enhancer region containing two functional PPARgamma binding
      sites in mouse catalase gene. Collectively, our findings suggest that PPARgamma
      plays a crucial role in the expression of catalase in adipocytes.

PMID- 18073139
TI  - Reactive oxygen species regulate Pseudomonas aeruginosa lipopolysaccharide
      induced MUC5AC mucin expression via PKC-NADPH oxidase-ROS-TGF-alpha signaling
      pathways in human airway epithelial cells.
AB  - Mucin overproduction is a hallmark of chronic inflammatory airway diseases, such
      as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Excessive
      production of mucin leads to airway mucus obstruction and contributes to
      morbidity and mortality in these diseases. The molecular mechanisms underlying
      mucin overproduction, however, still remain largely unknown. Here, we report that
      the bacterium P. aeruginosa, an important human respiratory pathogen causing
      cystic fibrosis, utilizes reactive oxygen species (ROS) to up-regulate MUC5AC
      mucin expression. Pseudomonas aeruginosa lipopolysaccharide (PA-LPS) induces
      production of ROS through protein kinase C (PKC)-NADPH oxidase signaling pathway
      in human epithelial cells. Subsequently, ROS generation by PA-LPS releases
      transforming growth factor-alpha (TGF-alpha), which in turn, leads to up-regulate
      MUC5AC expression. These findings may bring new insights into the molecular
      pathogenesis of P. aeruginosa infections and lead to novel therapeutic
      intervention for inhibiting mucin overproduction in patients with P. aeruginosa
      infections.

PMID- 18073140
TI  - Identification of poly(ADP-ribose) polymerase-1 as the OXPHOS-generated ATP
      sensor of nuclei of animal cells.
AB  - Our results show that in the intact normal animal cell mitochondrial ATP is
      directly connected to nuclear PARP-1 by way of a specific adenylate kinase
      enzymatic path. This mechanism is demonstrated in two models: (a) by its
      inhibition with a specific inhibitor of adenylate kinase, and (b) by disruption
      of ATP synthesis through uncoupling of OXPHOS. In each instance the de-inhibited
      PARP-1 is quantitatively determined by enzyme kinetics. The nuclear binding site
      of PARP-1 is Topo I, and is identified as a critical "switchpoint" indicating the
      nuclear element that connects OXPHOS with mRNA synthesis in real time. The
      mitochondrial-nuclear PARP-1 pathway is not operative in cancer cells.

PMID- 18073141
TI  - Expression analysis of the epithelial Na+ channel delta subunit in human melanoma
      G-361 cells.
AB  - Malignant melanoma is the most deadly form of skin cancer and its incidence is
      steadily increasing worldwide. The plasma membrane in melanoma cells possesses a
      variety of ion channels, so its profile is thought to lead to a novel target for
      medical treatment for malignant melanoma. Here we showed that human melanoma G
      361 cells expressed the epithelial Na(+) channel delta subunit (ENaC delta),
      which is largely unknown in physiological and pathological functions in non
      neuronal tissues. Expression analyses at the level of mRNA clearly revealed that
      ENaC delta transcript was strongly expressed in human melanoma cells using
      reverse transcription-polymerase chain reaction and cell-based in situ
      hybridization techniques. Other ENaC subunits (alpha, beta, and gamma) were also
      distributed in human melanoma cells. In addition, human melanoma cells possessed
      an abundant expression of ENaC delta protein by immunocytochemistry. These
      results provide an attractive target for drug development of malignant melanoma.

PMID- 18073142
TI  - Transcriptional regulation of FHL1 by TLX1/HOX11 is dosage, cell-type and
      promoter context-dependent.
AB  - TLX1/HOX11 encodes an NK-like homeodomain transcription factor that is both
      normally required for embryonic development and aberrantly expressed in T-cell
      acute lymphoblastic leukemia. Previous studies have shown that TLX1 can regulate
      target genes including ALDH1A1 and FHL1. However, whereas ALDH1A1 is consistently
      regulated by TLX1, endogenous FHL1 is only induced in a proportion of fibroblast
      or T-cell clones stably expressing TLX1. Here, we provide an explanation for
      these findings by demonstrating that the induction of FHL1, but not ALDH1A1,
      requires a high level of TLX1 expression in NIH 3T3 cells. In luciferase reporter
      assays, TLX1-mediated repression rather than activation of the FHL1 gene promoter
      and the magnitude of this effect was strongly influenced by the cellular
      background. Together, these results characterize TLX1 as a dual function
      regulator whose activity in respect to FHL1 is critically dependent upon its
      cellular concentration, as well as cell type and promoter context.

PMID- 18073143
TI  - Involvement of microtubule-associated protein 2 (MAP2) in oral cancer cell
      motility: a novel biological function of MAP2 in non-neuronal cells.
AB  - Microtubule-associated protein 2 (MAP2) has been better known for its well
      defined role primarily in neurite outgrowth during neuronal development. However,
      the biological functions of MAP2 in non-neuronal cells, such as epithelial cells,
      remain largely unknown. In the present study, we sought to investigate the
      cellular functions of MAP2 by separately establishing stable expression of two
      MAP2 isoforms, MAP2A and MAP2C, in oral squamous cell carcinoma, Ca9-22. Ectopic
      expression of MAP2A or MAP2C results in microtubule bundling predominantly at the
      cell periphery. Remarkably, overexpression of MAP2A but not MAP2C significantly
      promotes migration of Ca9-22 cells, whereas knockdown of MAP2A expression by
      specific siRNA oligos dramatically decreases cell migration of HaCaT, an
      immortalized keratinocyte cell line with abundant endogenous MAP2A. Furthermore,
      by immunohistochemical studies, MAP2A was shown to highly and selectively express
      in invasive oral cancer tissues, consistent with its motility-promoting cellular
      function revealed through in vitro assays. Thus, our findings have not only
      identified a novel role of MAP2 in non-neuronal cells, but also provided the
      first implication of MAP2 in malignant oral cancer tissues.

PMID- 18073144
TI  - Regulatory elements in the KlHEM1 promoter.
AB  - In Kluyveromyces lactis the gene encoding 5-aminolevulinate synthase, KlHEM1, is
      regulated at the transcriptional level by carbon source and oxygen availability.
      The KlHEM1 promoter, fused to the reporter lacZ gene, has been analysed by
      deletion and direct mutagenesis techniques in order to find regulatory elements
      functionally relevant in this transcriptional regulation. Two regulatory regions
      which contain the consensuses for KlGcr1p and KlMig1p binding are functional in
      the promoter. Regulation by carbon source is oppositely dependent on KlGcr1p and
      KlMig1p, as also confirmed by the use of mutants in these regulatory factors. A
      pyrimidine-rich element is necessary for full expression of KlHEM1 both in
      aerobic and hypoxic conditions. Deletion analyses show that a regulatory sequence
      included in the region -656 to -558 is also necessary to reach high KlHEM1
      expression in hypoxia. Hypoxic expression and repression caused in this condition
      by externally added deuteroporphyrin IX is independent of the consensuses for
      KlHap1p and KlBuf1p binding. Effects caused by disruption of the genes coding for
      the regulatory factors KlHap1p, KlRox1p and KlMot3p on KlHEM1 aerobic
      transcription do not fully explain the differences observed between normoxic and
      hypoxic expression.

PMID- 18073145
TI  - Emergence and trends of penicillin non-susceptible Streptococcus pneumoniae in
      Saudi Arabia and Kuwait - perspective and outstanding issues.
AB  - For many years in the past Streptococcus pneumoniae was uniformly susceptible to
      penicillin until the sudden and unexpected emergence of clinical infections
      caused by penicillin-resistant S. pneumoniae (PRSP) in 1967. Within the following
      decade, reports of nosocomial and community outbreaks of infections due to PRSP
      became widespread all over the world. Recent reports suggest that the incidence
      of resistance rates is rising in many countries although there are geographical
      variations in the prevalence and patterns of resistance between countries. The
      problem of antibiotic resistance is further compounded by the emergence of
      resistance to many beta-lactam antibiotics. The first report of PRSP in Saudi
      Arabia was in 1991. Barely a year after, PRSP infection was reported in Kuwait in
      1992. Since then, studies from various parts of these countries have recorded
      prevalence rates ranging from 6.2% in Riyadh to 34% in Jeddah and 20% to 56% in
      neighboring Kuwait. These suggest considerable variation in the prevalence of
      PRSP in different cities in the Saudi Kingdom and Kuwait. The mechanism of
      resistance is due to chromosomally mediated alteration of penicillin-binding
      proteins (PBPs), which are target sites for beta-lactam antibiotics. It would
      appear that the spread of PRSP strains in Saudi Arabia is driven by the selective
      pressure created by excessive use and misuse of antimicrobial agents made
      possible by the easy availability of these agents, often frequently obtainable
      over the counter. In Kuwait, irrational and misguided use of antibiotics may be
      the major driving force favoring the spread of PRSP. The serotypes of strains
      encountered in Saudi Arabia and Kuwait are almost identical, with serotypes 19,
      6, 15, 14 and 23 being the most common; together they constitute about 70% of the
      isolates circulating in these countries. In general, almost 90% of the serotypes
      included in the 23-polyvalent vaccine are present in the general population.
      However, a much lower percentage of these serotypes is found in the conjugated
      vaccines, which are more relevant to our communities. This paper reviews the
      emergence and the steady increase in the prevalence of penicillin-resistant
      pneumococcal strains in Saudi Arabia and Kuwait during the last 10 years. It
      discusses the trends, mechanisms of resistance and factors associated with the
      emergence, dissemination, and colonization of resistant organisms and suggests
      options available to clinicians for management of infections due to PRSP.

PMID- 18073146
TI  - Characterization of fluoroquinolone resistance mechanisms and their correlation
      with the degree of resistance to clinically used fluoroquinolones among
      Escherichia coli isolates.
AB  - DNA sequencing and real-time PCR were used to evaluate the gyrA and parC
      mutations, AcrAB efflux pump over-expression, and their correlation with high
      level resistance to fluoroquinolones in 74 fluoroquinolone-resistant clinical
      Escherichia coli isolates recently collected in Taiwan. RAPD analysis revealed
      high clonal diversity. Isolates with four to five mutations (especially Ser83Leu,
      Asp87Asn [or Asp87Tyr], and Ala93Thr in gyrA and Ser80Ile and Glu84Gly in parC)
      had increased resistance levels. The acrA gene was over-expressed in 51% of 74
      resistant isolates. The trend was towards increased fluoroquinolone MICs in
      isolates with both multiple mutations in the quinolone-resistance determining
      region (QRDR) and over-expression of the AcrAB efflux pump. Furthermore, acrA
      gene over-expression was significantly correlated with cross-resistance to beta
      lactams including piperacillin, amoxicillin, clavulanic acid, and cefazolin. In
      conclusion, mutations in the QRDR are the primary mechanism for increasing
      fluoroquinolone resistance, and in combination with efflux pump over-expression,
      contribute to high-level resistance.

PMID- 18073147
TI  - Antimicrobial susceptibility and beta-lactamase production of anaerobic and
      aerobic bacteria isolated from pus specimens from orofacial infections.
AB  - Most suppurative orofacial infections are polymicrobial. Information regarding
      the antimicrobial susceptibility of the microorganisms involved can be useful in
      the choice of an effective antibiotic therapy. In this study we determined the
      antimicrobial susceptibility of a total 235 anaerobic and aerobic bacteria
      recently isolated from pus specimens of orofacial infections. All the viridans
      streptococci were susceptible to penicillin, cefotaxime, cefoxitin, imipenem and
      levofloxacin. Imipenem and levofloxacin were active against 100% of the anaerobic
      Gram-positive organisms isolated. Among the anaerobic Gram-negative rods beta
      lactamase production was detected in all species except Campylobacter rectus.
      Amoxicillin-clavulanate, cefoxitin, imipenem and metronidazole were active
      against all the isolates of anaerobic Gram-negative species. Isolates resistant
      to erythromycin were found in all the species tested, however, resistance to
      clindamycin was only detected in Porphyromonas gingivalis and Bacteroides
      ureolyticus. Isolates resistant to levofloxacin were detected in P. gingivalis
      and Prevotella sp.

PMID- 18073148
TI  - Susceptibilities of Streptococcus pyogenes and Streptococcus pneumoniae to
      macrolides and telithromycin: data from an Italian multicenter study.
AB  - 687 isolates of Streptococcus pyogenes and 600 isolates of Streptococcus
      pneumoniae , isolated over the period 2002-2003 from specimens of different human
      origin obtained in 16 different Italian centres, were assayed for their
      susceptibilities to different macrolides and to telithromycin, and were
      investigated by PCR to detect their different erythromycin resistance genes.
      25.5% of the S. pyogenes isolates proved resistant to erythromycin, as well as to
      clarithromycin and azithromycin. 6.6% of the isolates proved non-susceptible to
      clindamycin. 4.9% of the isolates were non-susceptible to telithromycin. 22.3% of
      all erythromycin-resistant isolates exhibited cMLS B resistance, 50.3% iMLS B
      resistance, and 27.4% Mtype resistance. All cMLS B strains had the erm(B) gene,
      all M strains had the mef (A) gene, and no resistance genes were found in the
      erythromycin-susceptible strains. Roughly one quarter of the iMLS(B) strains had
      erm(A) and roughly three quarters erm(B). 35.2% of the S. pneumoniae isolates
      proved resistant to erythromycin, and virtually all of them also proved resistant
      to clarithromycin and azithromycin, too. Only 6.0% of the pneumococcal isolates
      were resistant to penicillin and a further 11.0% were intermediate. Only 0.2% of
      the isolates were nonsusceptible to telithromycin. 65.9% of all erythromycin
      resistant S. pneumoniae isolates had cMLS B resistance, 18.0% had iMLS B
      resistance, and 16.1% had M-type resistance. All the MLS B-resistant isolates had
      an erm(B) gene, and all the M-type isolates had a mef gene. We conclude that
      macrolide resistance of streptococci still persists in Italy with incidences as
      high as 40%, more often than not being characterised by the MLS B phenotype. The
      ketolide telithromycin, structurally related to macrolides and most likely to
      substitute for them in a number of clinical uses, is confirmed as being extremely
      active even against recent clinical streptococcal isolates.

PMID- 18073149
TI  - In vitro activity (MIC and MFC) of voriconazole, amphotericin B, and itraconazole
      against 192 filamentous fungi: the GISIA-2 study.
AB  - We evaluated the in vitro activity of voriconazole, amphotericin B, and
      itraconazole against 192 clinical mould isolates recovered in twenty Italian
      microbiology laboratories. The vast majority of isolates belonged to the genus
      Aspergillus (94.2%) with A. fumigatus (58.3%) being the most frequently isolated
      species. Antifungal susceptibility testing was performed using the broth
      microdilution method defined by the CLSI M38-A standard, and results were
      compared to those obtained with Sensititre panels. Aspergillus flavus ATCC 204304
      was employed as reference strain and results were within all expected ranges.
      Voriconazole's activity against the 192 mould isolates was comparable to that of
      amphotericin B and itraconazole: voriconazole MIC90 (CLSI 1 microg/ml, Sensititre
      1 microg/ml), itraconazole MIC90 (CLSI 0.5 microg/ml, Sensititre 0.5 microg/ml),
      amphotericin B MIC90 (CLSI 1 microg/ml, Sensititre 1 microg/ml). In conclusion,
      these in vitro data highlight voriconazole's broad spectrum activity against
      filamentous fungi and support its use as a first line agent for the treatment of
      fungal diseases.

PMID- 18073150
TI  - In-vitro activity of the synthetic protegrin IB-367 alone and in combination with
      antifungal agents against clinical isolates of Candida spp.
AB  - The in vitro activity of the peptide IB-367, alone or combined with either
      fluconazole (FLU) or amphotericin B (AMB), was investigated against 25 Candida
      isolates belonging to five species. IB-367 minimum inhibitory concentrations
      (MICs) ranged from 2.0 to 32 microg/ml and it was active against both FLU
      susceptible and - resistant isolates. A rapid fungicidal activity was observed.
      Synergism was documented in 41.6% and 44% of IB-367/FLU and IB-367/AMB
      interactions, respectively. Antagonism was never observed. The broad antifungal
      activity and the positive interactions with AMB and FLU suggest that IB-367
      represents a promising candidate against infections due to Candida spp.

PMID- 18073151
TI  - An 8-year evaluation of antibiotic consumption and antibiotic resistance among
      Streptococcus pneumoniae from in- and out-patients in Szeged, Hungary.
AB  - At the beginning of the 1990s, the prevalence of penicillin resistance of
      Streptococcus pneumoniae strains in Hungary was found to be extremely high (up to
      58% non-susceptible) in some studies, while in other publications the percentage
      of penicillin highly resistant strains was 0-2%. To see whether this was due to
      differences in methodology or the composition of the patient population studied,
      a retrospective evaluation was carried out of the penicillin, amoxicillin,
      ceftriaxone and macrolide resistance of all S. pneumoniae strains isolated from
      in- and outpatients in our laboratory between 1998 and 2005. Of the 2670 S.
      pneumoniae isolates only 5.58% was found to exhibit high-level resistance to
      penicillin, while resistance to amoxicillin, ceftriaxone and erythromycin was
      2.62%, 1.12% and 42.06%, respectively. During this period 6 (3.8%) of 155 S.
      pneumoniae strains isolated from invasive samples displayed high-level resistance
      to penicillin. Earlier surveillance data on penicillin resistance of S.
      pneumoniae may have been biased by the age groups affected by the infection, by
      whether the strain was isolated from an out-patient or an in-patient, and by
      whether the isolates were obtained from invasive samples. Our 8-year study using
      the NCCLS/CLSI methodology consequently revealed a low prevalence of high-level
      resistance to penicillin in S. pneumoniae strains obtained both from adults and
      children.

PMID- 18073152
TI  - Prevalence of antiretroviral drug resistance in treated HIV-1 infected patients:
      under the initiative of access to the NNRTI-based regimen in Thailand.
AB  - To determine the prevalence of antiretroviral resistance in treatment-failure HIV
      1 infected individuals, under the initiative of the non-nucleoside reverse
      transcriptase inhibitor (NNRTI)-based regimen in Thailand, plasma samples were
      collected from 1,376 HIV-1 infected patients, who were failing in their current
      HAART therapy during 2000-2004. They were stratified into 2 intervals: group one
      (1), 558 HIV-1 infected patients (2000-2002; before the initiative of access to
      HAART), and group two (2), 818 HIV-1 infected patients (2003-2004; after the
      initiative of access to HAART). Genotypic resistance testing was performed. The
      frequency of antiretroviral drug resistance in treatment-failure HIV-1 infected
      patients has significantly increased over time from 68.5% (382/558) during 2000
      2002 to 74.9% (613/818) during 2003-2004 (P<0.01). Resistance to NNRTI during
      2003-2004 (59.2%) was much higher than that during 2000-2002 (36.9%; P<0.001).
      However, the frequency of nucleoside reverse transcriptase inhibitor (NRTI) drug
      resistance was not significantly higher (P=0.153). We showed that this correlated
      with an increase in the NNRTI-based regimen prescribed during 2003-2004,
      especially the Thai-produced combination pill, GPO-VIR. Our finding also showed
      that a high level of genotypic drug resistance is associated with GPO-VIR (40.8%
      lamivudine, 40.6% stavudine, 43.8% nevirapine). In order to avoid the rapid
      emergence of resistant viruses in a resource-poor setting, a close surveillance
      of antiretroviral drug resistance is feasible and should be considered.

PMID- 18073153
TI  - A case series of macrolide treatment failures in community acquired pneumonia.
AB  - This was a retrospective, multi-center study of patients admitted to hospital
      with community-acquired pneumonia, caused by Streptococcus pneumoniae, after
      failing to respond to >2 days of outpatient macrolide therapy. 122 cases, treated
      between 2000-2004, were enrolled from 31 North American sites between January
      2004 - March 2005. Non-susceptible isolates (predominately low-level resistance:
      erythromycin MICs of 1-16 mcg/ml) were recovered from 87 patients (71%).
      Bacteremia was present in 63 patients (52%). The in-hospital mortality rate was
      5.7 %; all 7 patients who died were bacteremic, 6 had a non-susceptible isolate.
      We report here the largest series of macrolide failures published to date. The
      patients were notable for their high rates of macrolide resistance, bacteremia,
      and mortality. High-level macrolide resistance remains rare among US patients
      failing outpatient macrolides. The majority of cases and virtually all of the
      mortality occurred in patients with low-level resistant strains.

PMID- 18073154
TI  - Comparative cytotoxicity of C-1311 in colon cancer in vitro and in vivo using the
      hollow fiber assay.
AB  - The aim of this study was to investigate the antiproliferative effects of C-1311
      (Symadex), a member of the imidazoacridinone family, in human colorectal cancer
      cells. In the in vitro screen, C-1311 led to the most prominent growth inhibition
      in HT29, HCT116, and COLO205 cell lines when compared to oxaliplatin, CPT-11,
      DFUR, 5-FU and capecitabine. The GI(50)values for C-1311 ranged from 0.12 to 0.83
      microM and the TGI concentrations (resulting in total growth inhibition) were 6-
      to 13-fold lower than those of other agents. In the hollow fiber assay in vivo, C
      1311 caused 77% growth inhibition of HT29 in the intraperitoneal site as compared
      to paclitaxel (17% growth inhibition). In the subcutaneous site, C-1311 produced
      57% growth inhibition while paclitaxel showed no cell growth inhibition effects.
      This unique cytotoxicity profile of C-1311 warrants further investigation and
      supports its clinical development in colon cancer patients. Symadex (C-1311) is
      currently in phase 2 clinical trials.

PMID- 18073155
TI  - Inhibition of osteosarcoma cell proliferation by the Hedgehog-inhibitor
      cyclopamine.
AB  - Osteosarcomas (OS) are the most frequent primary malignant bone tumors in humans.
      Even though OS are chemosensitive, about 30% of patients must be considered poor
      responders and consequently have a dismal long term prognosis. The Hedgehog (Hh)
      gene is crucial in the signalling pathways of proliferation and differentiation
      during embryonic development. There is evidence that uncontrolled activation of
      this pathway results in specific types of cancer and that inhibition of Hh
      signalling is able to suppress tumour growth and to induce apoptosis of
      neoplastic cells. This study investigates the impact of the steroidal alkaloid
      and Hh-inhibitor cyclopamine on osteosarcoma cells. Thus we demonstrate the
      drug's impact on cellular proliferation, cell cycle cell death as well as the
      cells' metabolism. We here demonstrate that cyclopamine exhibits a high efficacy
      against the osteosarcoma cell lines HOS, SaOS and OS-KA, a self-established
      primary osteosarcoma cell line. In particular, cyclopamine is able to inhibit
      proliferation and to promote cell death. Our results provide evidence for the
      potency of the Hh-inhibitor cyclopamine as a future treatment of osteosarcomas.

PMID- 18073156
TI  - IL-2 induces and altered CD4/CD8 ratio of splenic T lymphocytes from transgenic
      mice overexpressing the glucocorticoid-induced protein GILZ.
AB  - We used transgenic mice to investigate the effect of IL-2 stimulation on T
      lymphocyte functions of GILZ-overexpressing splenic T cells. When compared to
      their controls, T cells from transgenic mice underwent normal activation after
      stimulation with anti-CD3 plus anti-CD28 monoclonal antibodies, as evaluated by
      CD25 expression, CD2 up-regulation and proliferation. IL-10, IL-13 and IFN-gamma
      increased more consistently in CD3/CD28-triggered TG compared to WT splenic
      CD4(+)cells. Analysis of the CD4(+)and CD8(+)T cells demonstrated a decreased
      CD4(+)/CD8(+)T-cell ratio (1:1 instead of 1:2) in response to IL-2 stimulation,
      possibly due to an unresponsiveness of IL-2 receptor beta and/or gamma chains.
      Finally, the total number of T cells was significantly increased in aged mice and
      this was due to the augmentation of CD4(+)T cells. These results support the
      hypothesis that GILZ regulates, at least in part, peripheral T-cell functions by
      influencing their responsiveness to IL-2.

PMID- 18073157
TI  - Phase II trial of a biweekly regimen of fluorouracil and leucovorin plus
      irinotecan in patients with previously untreated advanced gastric cancer.
AB  - To investigate the therapeutic value and safety of the biweekly regimen of 5
      fluorouracil (5-FU) and leucovorin (LV) plus irinotecan (CPT-11) in patients with
      previously untreated advanced gastric cancer (AGC). A total of 50 patients (M/F
      35/15; median age = 65) with AGC, none of whom had received chemotherapy for
      advanced disease, were accrued in this trial. Fifteen patients (30%) were 70
      years old or older. At the time of their accrual, cytotoxic chemotherapy,
      consisting of LV 100 mg/m(2) (2-hour i.v. infusion) followed by 5-FU 400 mg/m(2)
      (bolus) and 5-FU 600 mg/m(2) (22-hour continuous infusion) on therapeutic days 1
      and 2 plus CPT-11 180 mg/m(2) (1-hour infusion) on day 1, was initiated.
      Treatment courses were repeated every 2 weeks until evidence of progressive
      disease, unacceptable toxicity or withdrawal of consent. All patients were
      assessable for toxicity and 48 of 50 for response evaluation, having completed at
      least four courses of chemotherapy. Complete response was achieved in 2 patients
      (4%, intent to treat) and partial response in 16 (32%) (overall response rate,
      36%; 95% confidence interval [CI]: 22%-50%). Twenty-four patients (48%) had
      stable disease and 6 patients (16%) progressed. The median time to progression
      was 8 months (95% CI: 6-10 months) and median overall survival 14 months (95% CI:
      6-22 months). Between the subgroups of patients <70 years old and 70 or older,
      there were no significant differences in efficacy. One toxic death occurred.
      Treatment tolerance was generally mild to moderate and easy to treat. The main
      grade 3/4 toxicities were neutropenia (32%), diarrhea (16%), and anemia (8%).
      Grade 3-4 neutropenia was the only treatment-related serious adverse event
      significantly more common in patients older than those aged <70 (53.3% vs 22.8%,
      respectively; P = 0.03). Our data suggest that the biweekly regimen of LV and 5
      FU plus CPT-11 in untreated patients with AGC is active and has an acceptable
      safety profile. Further evaluation of this regimen seems to be warranted in a
      phase III trial.

PMID- 18073158
TI  - Gemcitabine combined with oxaliplatin (GEMOX) as salvage treatment in elderly
      patients with advanced ovarian cancer refractory or resistant to platinum: a
      single institution experience.
AB  - Both oxaliplatin (OXA) and gemcitabine (GEM) have shown single agent activity in
      patients with recurrent ovarian cancer. Response rates to second-line therapies
      remain low and there is a need to develop more effective regimens. In view of the
      synergistic effect of using GEM followed by OXA, we studied these agents in
      elderly patients with recurrent ovarian cancer refractory or resistant to first
      line chemotherapy using platinum with or without paclitaxel. The aim of the study
      was to evaluate the efficacy and toxicity of combination GEM 1000 mg/m(2) Day 1
      i.v. and OXA 100 mg/m(2) in 2h infusion Day 2; treatment was repeated every 2
      weeks for 6 courses or until progression of disease or intolerable toxicity. The
      study was monoinstitutional and started in November 2002. 21 patients, median age
      68.6 years (range 65-82) have been treated. Median Performance Status was 0-1,
      all had at least 1 prior platinum based chemotherapy and 11 had received also a
      taxane. Patients received a median of 6 cycles of treatment (range 4-11). There
      were 2 patient (9%) with complete response, 3 patients (14%) achieved a partial
      response. Low profile toxicity (grade 1-2, WHO criteria) was observed:
      nausea/vomiting 52%, thrombocytopenia 13%, neuropathy 28%. The GEMOX combination
      is well tolerated and even in this small group of patients, encouraging responses
      were documented.

PMID- 18073159
TI  - Mitoxantrone plus vinorelbine in pretreated patients with metastatic breast
      cancer.
AB  - Vinorelbine and mitoxantrone have both been demonstrated to have significant
      antitumor activity in patients with breast cancer. The aim of this study was to
      evaluate the efficacy and safety of the combination as second or third line
      treatment in patients with metastatic breast cancer (MBC). Fifty-one previously
      treated patients with MBC were enrolled from October 2001 to May 2004 and 48 were
      eligible for evaluation. Median age was 59 years (range 33-82) and ECOG
      performance status was < or =2. Distant sites of metastasis were as follows:
      liver 64%, bone 49%, lung 36%, lymph nodes 6%, skin 4%, brain 2% and other sites
      6%. All patients received vinorelbine 20 mg/m(2), D1+8 and mitoxantrone 10
      mg/m(2) D8 every 21 days for 6 cycles. All eligible patients were analyzed for
      toxicity and response. Two patients (4%) achieved complete response and 12
      (25.5%) partial response. The objective overall response rate was 29.5% (95%
      confidence interval [CI] 17 - 45), 9 (19%) patients had stable disease, 17 (36%)
      had progressive disease and 7 (15%) were non-evaluable. After a median follow up
      of 18 months, overall survival was 13 months (range 0.8 - 38+) and median time to
      disease progression was 5 months (range 1 - 32). A total of 280 cycles was
      delivered. The relative dose intensities of mitoxantrone and vinorelbine were 79%
      and 77%, respectively. Toxicities (grade III-IV) were as follows: leukopenia 18
      (38%), neutropenia 21 (45%), thrombocytopenia 1 (2%), anemia 4 (8.5%), alopecia 2
      (4%) and constipation 1 (2%). Febrile neutropenia was recorded in one patient.
      There were no treatment related deaths. The combination of mitoxantrone and
      vinorelbine is an effective regimen with manageable toxicity in pretreated
      patients with advanced breast cancer.

PMID- 18073160
TI  - The impact of the introduction of irinotecan and oxaliplatin on the outcome of
      patients with advanced colorectal cancer.
AB  - The effectiveness of oxaliplatin and irinotecan in advanced colorectal cancer
      therapy has been shown by many randomized clinical trials. We developed a
      retrospective study on patients treated in the clinical practice. The main
      inclusion criteria were: diagnosis of unresectable colorectal adenocarcinoma and
      having undergone chemotherapy. Univariate and multivariate analyses were
      performed to identify the prognostic factors of survival. The study included 286
      consecutive patients. Three factors were associated with worse survival: high
      CA19-9 levels (p=0.003), schedules without new regimens (p=0.031) and weight loss
      (p=0.070). The use of new regimens was associated with a significant improvement
      in median survival (15 to 10 months, p<0.001). Although the new regimens improved
      survival in clinical practice, the median gain is smaller than that reported in
      randomized trials. The palliative intent of these therapies should not be
      forgotten in order to improve quality of life rather than absolute survival.

PMID- 18073161
TI  - Mutant prevention concentrations of tetracycline, rifampicin and ciprofloxacin
      for Brucellae melitensis.

PMID- 18073162
TI  - Generation of resistant mutants of Mycobacterium chelonae and Mycobacterium
      fortuitum after exposure to subinhibitory concentrations of clarithromycin and
      moxifloxacin.

PMID- 18073164
TI  - Executive summary of the Gulf Cooperation Council practice guidelines for the
      management of community-acquired pneumonia.

PMID- 18073165
TI  - Rationale for producing evidence-based guidelines for community-acquired
      pneumonia in the Gulf Corporation Council.
AB  - World-wide community-acquired pneumonia (CAP) is a common respiratory tract
      infection and is now a growing public health concern in the GCC region. Practice
      guidelines are derived statements which lead to informed clinical decision
      making. National and regional guidelines have been developed in North America,
      South America, South Africa and Western Europe to assist practitioners managing
      patients with CAP and have demonstrated to improve patients outcome. Four years
      have elapsed since the publication of the Saudi Arabian CAP guideline and notable
      changes in the area of CAP demand revision of this earlier document. We expanded
      previous guidelines to a regional level in a number of ways: by incorporating
      changes in antimicrobial resistance profiles in the region, by considering the
      regional availability of antibiotics and diagnostic procedures, by including
      emerging data on new advancements in diagnosis and treatment of CAP and, finally,
      by adopting an evidence-based approach in grading relevant data. The current
      document seeks to target primary care physicians who manage most patients with
      CAP in the GCC region. All available and relevant peer reviewed studies published
      until June 2007 were considered in the literature review. Based on the strength
      of the evidence, we graded our recommendations to high-level (Level I), moderate
      level (Level II), and low-level (Level III) evidence.

PMID- 18073167
TI  - Clinical presentation and diagnostic workup for community-acquired pneumonia: the
      Gulf Corporation Council CAP Working Group consensus statement.
AB  - Community-acquired pneumonia (CAP) is diagnosed on the basis of a suggestive
      history and compatible physical findings and new infiltrates on a chest
      radiograph. No criteria or combination of criteria based on history and physical
      examination have been found to be gold standard. With the rise in elderly Gulf
      Cooperation Council (GCC) residents, CAP is likely to present with non-classical
      manifestations such as somnolence, new anorexia, and confusion and carries a
      worse outcome than CAP in their younger counterparts. Tuberculosis should be
      considered in the differential diagnosis of unresolving CAP in the GCC region.
      Diagnostic work up depends on severity of CAP, clinical course and underlying
      risk factors.

PMID- 18073166
TI  - Microbiology of community-acquired pneumonia in the Gulf Corporation Council
      states.
AB  - In spite of advances in microbiological and serological investigations over the
      last two decades, etiological attribution remains difficult in community-acquired
      pneumonia (CAP). Even after exhaustive investigation, the etiology of CAP remains
      unknown in up to 50% of patients. Common pathogens include Streptococcus
      pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In addition,
      several investigators document the importance of atypical pathogens including
      Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila in the
      etiology of CAP in the GCC region. Increasingly, other etiologies, particularly
      influenza viruses, varicella zoster virus and Mycobacterium tuberculosis, have
      been recognized as causative pathogens of CAP within the region. Rates of
      antimicrobial resistance of S. pneumoniae and other pathogens are rising in the
      Gulf Corporation Council (GCC) region and susceptibility profiles of antibiotics
      against intracellular pathogens such as Chlamydophila pneumoniae and Mycoplasma
      pneumoniae are not routinely performed. Injudicious prescribing and over-use of
      antibiotics drive much resistance. The GCC CAPWG calls for urgent governmental
      regulations to limit and monitor antibiotic prescription in the GCC region.

PMID- 18073168
TI  - Management and prevention strategies for community-acquired pneumonia in the Gulf
      Corporation Council.
AB  - Risk factors identify likelihood and severity of community-acquired pneumonia
      (CAP) and may allow prognostication. Prognostic factors can focus resources and
      efforts on those who may need special observation. Several risk assessment tools
      are used to estimate the severity of CAP and whether these tools can be used to
      predict outcomes, to determine disposition or even used to determine ICU level of
      care is hotly under debate. Treating CAP depends on age and comorbidities, as
      well as local epidemiology and disease severity. The current guidelines for
      managing CAP categorize patients with CAP into the healthy outpatient, the
      outpatient with modifying factors or comorbidities, the inpatient with CAP and
      patients requiring intensive care unit admission. These guidelines took into
      account regional bacteriology, antibiotic resistance data and available
      antibiotics to formulate recommendations. Preventive strategies for CAP include
      the administration of pneumococcal and influenza vaccine in selected populations
      at risk.

PMID- 18073169
TI  - Bronchiolitis today.

PMID- 18073170
TI  - Respiratory syncytial virus infection and recurrent wheezing: what next?
AB  - Recent literature has provided evidence of a link between early RSV infection and
      chronic respiratory morbidity (recurrent wheezing, reactive airway disease and
      asthma). The mechanism of this association is not well understood but both
      genetic and environmental factors are involved. The classical studies from
      Sweden, Tucson and Finland are briefly summarized. Moreover new data concerning a
      recent multi-center international study on this topic are presented. The study,
      which enrolled 191 preterm infants (<or=35 wGA) who had received pelivizumab
      before 6 months of age and 230 who had never received pelivizumab, suggests that
      prevention of respiratory syncytial virus (RSV) lower respiratory tract
      infections (LRTIs) with pelivizumab may reduce subsequent recurrent wheezing in
      premature infants. The INDEX study, a prospective study, will provide a useful
      contribution to the definition of epidemiological data on respiratory infection
      in preterm infants in Italy. Additional research is required to more fully
      understand the mechanism by which RSV leads to wheezing.

PMID- 18073171
TI  - Bronchiolitis: the new American Academy of Pediatrics guidelines.
AB  - Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization for
      lower respiratory tract infections (LRTI) in young children worldwide. RSV is an
      important cause of LRTI in infants and a variety of factors, such as gender, age
      at admission, gestational age, birth weight, and exposure to tobacco smoke and
      breast feeding may affect the prevalence of RSV-related disease and, possibly,
      the risk of developing asthma-like symptoms during the school years. AAP in 2006
      formulated the new guidelines on diagnosis and management of bronchiolitis,
      giving recommendations on different conditions requesting clinical decisions also
      in terms of prevention.

PMID- 18073172
TI  - Elements of pharmacoeconomics.

PMID- 18073173
TI  - Chorioamnionitis.
AB  - Chorioamnionitis is an inflammation of the placental membranes induced by
      microorganisms which reach the endometrial cavity from the vagina and uterine
      cervix. Premature labor frequently depends on infections. In patients with
      premature rupture of membranes (PROM) antibiotic treatment can prevent intra
      amniotic inflammation if it is absent at admission. In spite of antibiotic
      treatment started immediately after the PROM in 218 patients, the
      chorioamnionitis did not prevent delivery in 41 patients within 48 hours of PROM.
      In the presence of a previous chorioamnionitis, antibiotic treatment cannot
      prevent premature labor, whereas it can prevent infection and lead to a longer
      duration of pregnancy if PROM does not depend on previous infection.

PMID- 18073174
TI  - Epidemiology of neonatal infections.
AB  - The World Health Organization estimates that more than 4 million neonates die
      each year and 98% of these deaths occur in developing countries. Infections are
      among the main causes of neonatal mortality. The neonatal health is intrinsically
      linked to the mother's health and the care she receives before, during and
      immediately after delivery. If in resource-rich countries improvements in
      perinatal conditions, prevention and management of fetal-neonatal infections have
      reduced the burden of neonatal morbidity and mortality, in resource-limited areas
      they have only just improved and many barriers remain still to be overcome.
      Prematurity is often due to fetal infections and represents a significant risk
      factor for nosocomial infections.

PMID- 18073175
TI  - Group B streptococcus: early- and late-onset infections.
AB  - Group B streptococcus has emerged as a prominent neonatal pathogen in developed
      countries since the late 1960s. The incidence of disease remained fairly constant
      until the 1990 s, when prevention efforts increased. American consensus
      guidelines were endorsed in the mid 1990 s; since then a decrease in disease
      incidence has been reported in the United States. This review summarizes the main
      issues regarding the prevention of neonatal infection and presents aspects of
      group B streptococcal disease with the first population data recently obtained in
      a northern region of Italy.

PMID- 18073176
TI  - Bacterial sepsis.
AB  - Bacterial sepsis remain a major cause of mortality and morbidity in the newborn.
      The severe outcome of neonatal sepsis, despite the advances in perinatal and
      neonatal care and use of potent antibiotics, is related to the neonatal reduced
      immune defenses and the complex interactions between the infecting microorganism
      and the host responses. An early diagnosis, based on the clinical picture, the
      isolation of microorganisms and the positivity of inflammatory indexed, is
      mandatory. A timely treatment should be aimed to the elimination of pathogens
      with antimicrobials. Intravenous immunoglobulin and hematopoietic growth factors
      may be considered to improve the disturbed immune homeostases.

PMID- 18073177
TI  - New diagnostic tools for neonatal sepsis: the role of a real-time polymerase
      chain reaction for the early detection and identification of bacterial and fungal
      species in blood samples.
AB  - Early diagnosis and treatment of neonatal sepsis are essential to prevent severe
      and life threatening complications. Consequently, rapid diagnostic tests capable
      to differentiate infected from non-infected newborns have the potential to make a
      significant impact on neonatal care. A new real-time polymerase chain reaction
      (PCR; LightCycler SeptiFast test M GRADE) has been proposed in the routine
      assessment of neonatal sepsis for the detection and identification of bacterial
      and fungal DNA from microorganisms which cause approximately 90% of all blood
      stream infections. The LightCycler SeptiFast test can detect and identify
      simultaneously the 25 most important bacterial and fungal species causing
      bloodstream infections within few hours by using a small volume of a single whole
      blood sample. Real-time PCR can be easily incorporated into the hospital setting
      for term or near-term infants admitted to the neonatal intensive care unit for
      sepsis evaluation.

PMID- 18073178
TI  - Biochemical markers for the early assessment of neonatal sepsis: the role of
      procalcitonin.
AB  - Procalcitonin (PCT) is the precursor of calcitonin, normally synthesized in the C
      cells of the thyroid gland. Systemic inflammation and sepsis induce PCT
      production by various cell types, including hepatocytes, nephrons, monocytes. PCT
      begins to rise four hours after exposure to bacterial endotoxins, peaking at six
      to eight hours, and remaining raised for at least 24 hours with a half-life of 25
      30 hours. Serum PCT levels significantly increase in systemic bacterial
      infection, necrotizing enterocolitis, and during both early and late onset
      neonatal sepsis. By using a cut-off limit of 0,5 microg/L, the PCT positive
      likelihoud ratio was found of 12.5. PCT has a theoretical advantage as a marker
      of systemic induction in sepsis and its half-life suitable for daily monitoring
      of disease progress. PCT may be useful in assessing the severity of infection,
      following the progress of treatment, and predicting outcomes.

PMID- 18073179
TI  - Therapeutic drug monitoring of gentamicin in neonatal intensive care unit:
      experience in 68 newborns.
AB  - A proper dosing regimen is fundamental when antibiotics with a low therapeutic
      index, as aminoglycosides (AMG), are used. AMG pharmacokinetics present a strong
      interindividual and intraindividual variability in neonates; in the premature
      neonate AMG clearance is reduced and the half-life is longer, leading to higher
      serum trough concentrations. Neonates may require therapeutic drug monitoring
      (TDM) and a "tailored" therapeutic regimen. The aim of this work is to present
      our personal experience wtih TDM of gentamicin in 68 newborns and to compare it
      with data available in the literature.

PMID- 18073180
TI  - Neonatal fungal infections: the state of the art.
AB  - Candida spp is the 3rd most frequent cause of sepsis in preterm infants, with
      high attributable mortality and poor outcome. Neonatal fugal infections include
      bloodstream, urine, cerebrospinal and peritoneal infections. Preterm infants
      display specific, often unavoidable, risk factors for SFI, with fungal
      colonization being the most significant one. Prompt treatment does not prevent
      poor long-term neurodevelopmental outcomes. Thus, prevention is the milestone,
      and should mainly rely on the administration of targeted prophylactic fluconazole
      to high-risk infants, as recently demonstrated by a large Italian multicenter
      study. As prevention is key in pediatrics, finally we can deliver this to this
      vulnerable population.

PMID- 18073181
TI  - Cytomegalovirus infection: the state of the art.
AB  - Cytomegalovirus (CMV) is the leading cause of congenital infection in humans and
      constitutes a major public health problem. Congenitally infected infants, both
      symptomatic and asymptomatic at birth, may develop sequelae, particularly
      sensorineural hearing loss (SNHL) and brain damage. Transmission of the virus
      from mother to fetus can occur during either primary or recurrent maternal
      infection; however it is much higher in primary infected mothers than in mothers
      with preconceptional immunity. Routine CMV screening for primary infection during
      pregnancy constitutes a controversial issue, because of the lack of prenatal
      recommended therapy for congenital CMV infection. Ganciclovir may be used to
      treat neonates with symptoms at birth. Despite advances in antiviral therapy,
      congenitally infected infants, both symptomatic and asymptomatic at birth, need a
      follow up evaluation to detect sequelae. Congenital CMV infection cna be
      diagnosed at birth by using a test based on detection of viral DNA by PCR in
      dried blood spots (Guthrie card) collected on filter paper in the first days of
      life. Therefore, universal newborn screening for CMV by using DBS test should be
      recommended to detect sequelae as early as possible, so that infants can receive
      intervention promptly.

PMID- 18073182
TI  - Breastfeeding and cytomegalovirus infections.
AB  - Perinatal cytomegalovirus (CMV) infection has recently become a matter of some
      debate. It is acquired by the newborn mainly via breast milk and though this has
      practically no consequences in term newborns, it may cause severe symptomatic
      disease in preterm newborns. Almost all CMV-seropositive women eliminate the
      virus via their milk; freezing breast milk at -20 degrees C and pasteurization
      may respectively reduce or eliminate the viral load. No evidence has yet been
      found in preterm neonates for sequelae related to CMV infection acquired via
      breast milk. The administration of fresh breast milk to very premature neonates
      who constitute a population at risk is controversial.

PMID- 18073183
TI  - Antibiotics in neonatal intensive care units (NICUs).
AB  - Antibiotics, the most effective tools against pathogens, are overused in neonatal
      intensive care units (NICUs). Prolonged and unnecessary empirical use of broad
      spectrum antibiotics selects resistant bacteria and increases the risk of sever
      fungal infections. Judicious use of antibiotics and development of appropriate
      intervention strategies and policies in order to reduce antibiotic use should be
      a primary objective in all NICUs. The choice of the best empirical antibiotic
      regiment should be base on the age of the infant, on the clinical signs and on
      the pharmacokinetics of the drug, but the narrowest spectrum antibiotics should
      be used.

PMID- 18073184
TI  - Rapid control of two outbreaks of Serratia marcescens in a Northern Italian
      neonatal intensive care unit.
AB  - Serratia marcescens is a recognized cause of outbreaks in neonatal intensive care
      units (NICUs). The aim of the present study was to investigate two nosocomial
      outbreaks of S. marcescens that occurred in an NICU in Northern Italy. In order
      to determine the origin of the outbreaks and the associated morbidity and
      mortality of S. marcescens infections and epidemiological investigation was
      established including molecular typing of the isolates. Containment of the
      outbreaks was achieved by means of strict hygienic measure and cohort nursing of
      the infected and/or colonized infants. We experimented with the use of probiotics
      as an infection control measure.

PMID- 18073185
TI  - A structural basis for enhancement of long-term associative memory in single
      dendritic spines regulated by PKC.
AB  - Using both scanning confocal and electron microscopic morphometric measurements,
      we analyzed single dendritic spines of CA1 pyramidal cells in the hippocampi of
      water maze-trained rats vs. controls. Two days after completion of all training,
      we observed a memory-specific increase in the number of mushroom spines-all of
      which make synaptic contacts-but not in the numbers of filopodia or stubby or
      thin spines, as quantified with double-blind protocols in both scanning confocal
      and electron microscopic images. This memory-specific increase of mushroom spine
      number was enhanced by the PKC activator and candidate Alzheimer's disease
      therapeutic bryostatin, blocked by the PKCalpha-isozyme blocker Ro 31-8220, and
      accompanied by increases in the number of "perforated" postsynaptic densities,
      increased numbers of presynaptic vesicles, and the increased occurrence of double
      synapse presynaptic boutons associated with the mushroom spines. These and other
      confocally imaged immunohistochemical results described here involving PKC
      substrates indicate that individual mushroom spines provide structural storage
      sites for long-term associative memory and sites for memory-specific
      synaptogenesis that involve PKC-regulated changes of spine shape, as well as PKC
      regulated changes of pre- and postsynaptic ultrastructure.

PMID- 18073186
TI  - Statin-induced heme oxygenase-1 increases NF-kappaB activation and oxygen radical
      production in cultured neuronal cells exposed to lipopolysaccharide.
AB  - With potentially neuroprotective properties, heme oxygenase-1 (HO-1) has been
      suggested to be the main mediator of cholesterol-independent anti-inflammatory
      and antioxidant actions of statins. However, we had demonstrated that simvastatin
      induced HO-1 increased apoptosis of Neuro 2A cells in glucose deprivation, and
      iron production from HO-1 activity may be responsible for the toxicity. This
      study was designed to explore the effect of simvastatin-induced HO-1 on cultured
      Neuro 2A and C6 cells exposed to lipopolysaccharide (LPS). We found that the HO-1
      upregulation was significantly associated with increased nuclear factor kappa B
      (NF-kappaB) activation, manifested as IkappaBalpha phosphorylation and p65
      nuclear translocation, as well as increased production of superoxides. Inhibition
      of the induced HO-1 by zinc protoporphyrin reduced the increased NF-kappaB
      activation and superoxides production. RNA interference with HO-1 siRNA reduced
      the expression of HO-1 transcripts and protein as well as oxygen radical
      production. Addition of the iron chelator desferrioxamine to reduce the
      accumulation of ferric iron from heme by HO-1 resulted in blockade of the
      aggravated oxygen radical production. There was no significant effect on
      production of oxygen radicals under these conditions in the presence of a CO
      donor (RuCO) or a CO scavenger (hemoglobin). In addition, the viable cells were
      significantly decreased in 48 h in those cells receiving simvastatin pretreatment
      plus LPS compared to those in control or exposed to simvastatin or LPS alone.
      This study revealed that simvastatin-induced HO-1 led to increased NF-kappaB
      activation and superoxides production in the neuronal cells when exposed to LPS,
      and iron production may play a role in such a response.

PMID- 18073187
TI  - Modelling the results of health promotion activities in Switzerland: development
      of the Swiss Model for Outcome Classification in Health Promotion and Prevention.
AB  - This paper describes the Model for Outcome Classification in Health Promotion and
      Prevention adopted by Health Promotion Switzerland (SMOC, Swiss Model for Outcome
      Classification) and the process of its development. The context and method of
      model development, and the aim and objectives of the model are outlined.
      Preliminary experience with application of the model in evaluation planning and
      situation analysis is reported. On the basis of an extensive literature search,
      the model is situated within the wider international context of similar efforts
      to meet the challenge of developing tools to assess systematically the activities
      of health promotion and prevention.

PMID- 18073188
TI  - DBD--taxonomically broad transcription factor predictions: new content and
      functionality.
AB  - DNA-binding domain (DBD) is a database of predicted sequence-specific DNA-binding
      transcription factors (TFs) for all publicly available proteomes. The proteomes
      have increased from 150 in the initial version of DBD to over 700 in the current
      version. All predicted TFs must contain a significant match to a hidden Markov
      model representing a sequence-specific DNA-binding domain family. Access to TF
      predictions is provided through http://transcriptionfactor.org, where new search
      options are now provided such as searching by gene names in model organisms,
      searching for all proteins in a particular DBD family and specific organism. We
      illustrate the application of this type of search facility by contrasting trends
      of DBD family occurrence throughout the tree of life, highlighting the clear
      partition between eukaryotic and prokaryotic DBD expansions. The website content
      has been expanded to include dedicated pages for each TF containing domain
      assignment details, gene names, links to external databases and links to TFs with
      similar domain arrangements. We compare the increase in number of predicted TFs
      with proteome size in eukaryotes and prokaryotes. Eukaryotes follow a slower rate
      of increase in TFs than prokaryotes, which could be due to the presence of splice
      variants or an increase in combinatorial control.

PMID- 18073189
TI  - Remediation of the protein data bank archive.
AB  - The Worldwide Protein Data Bank (wwPDB; wwpdb.org) is the international
      collaboration that manages the deposition, processing and distribution of the PDB
      archive. The online PDB archive at ftp://ftp.wwpdb.org is the repository for the
      coordinates and related information for more than 47 000 structures, including
      proteins, nucleic acids and large macromolecular complexes that have been
      determined using X-ray crystallography, NMR and electron microscopy techniques.
      The members of the wwPDB-RCSB PDB (USA), MSD-EBI (Europe), PDBj (Japan) and BMRB
      (USA)-have remediated this archive to address inconsistencies that have been
      introduced over the years. The scope and methods used in this project are
      presented.

PMID- 18073190
TI  - GenBank.
AB  - GenBank (R) is a comprehensive database that contains publicly available
      nucleotide sequences for more than 260 000 named organisms, obtained primarily
      through submissions from individual laboratories and batch submissions from large
      scale sequencing projects. Most submissions are made using the web-based BankIt
      or standalone Sequin programs and accession numbers are assigned by GenBank staff
      upon receipt. Daily data exchange with the European Molecular Biology Laboratory
      Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures
      worldwide coverage. GenBank is accessible through NCBI's retrieval system,
      Entrez, which integrates data from the major DNA and protein sequence databases
      along with taxonomy, genome, mapping, protein structure and domain information,
      and the biomedical journal literature via PubMed. BLAST provides sequence
      similarity searches of GenBank and other sequence databases. Complete bimonthly
      releases and daily updates of the GenBank database are available by FTP. To
      access GenBank and its related retrieval and analysis services, begin at the NCBI
      Homepage: www.ncbi.nlm.nih.gov.

PMID- 18073191
TI  - The telomerase database.
AB  - Telomerase is a ribonucleoprotein enzyme that extends DNA at the chromosome ends
      in most eukaryotes. Since 1985, telomerase has been studied intensively and
      components of the telomerase complex have been identified from over 160
      eukaryotic species. In the last two decades, there has been a growing interest in
      studying telomerase owing to its vital role in chromosome stability and cellular
      immortality. To keep up with the remarkable explosion of knowledge about
      telomerase, we compiled information related to telomerase in an exhaustive
      database called the Telomerase Database (http://telomerase.asu.edu/). The
      Telomerase Database provides comprehensive information about (i) sequences of the
      RNA and protein subunits of telomerase, (ii) sequence alignments based on the
      phylogenetic relationship and structure, (iii) secondary structures of the RNA
      component and tertiary structures of various subunits of telomerase, (iv)
      mutations of telomerase components found in human patients and (v) active
      researchers who contributed to the wealth of current knowledge on telomerase. The
      information is hierarchically organized by the components, i.e. the telomerase
      reverse transcriptase (TERT), telomerase RNA (TR) and other telomerase-associated
      proteins. The Telomerase Database is a useful resource especially for researchers
      who are interested in investigating the structure, function, evolution and
      medical relevance of the telomerase enzyme.

PMID- 18073192
TI  - Protein evolution by hypermutation and selection in the B cell line DT40.
AB  - Genome-wide mutations and selection within a population are the basis of natural
      evolution. A similar process occurs during antibody affinity maturation when
      immunoglobulin genes are hypermutated and only those B cells which express
      antibodies of improved antigen-binding specificity are expanded. Protein
      evolution might be simulated in cell culture, if transgene-specific hypermutation
      can be combined with the selection of cells carrying beneficial mutations. Here,
      we describe the optimization of a GFP transgene in the B cell line DT40 by
      hypermutation and iterative fluorescence activated cell sorting. Artificial
      evolution in DT40 offers unique advantages and may be easily adapted to other
      transgenes, if the selection for desirable mutations is feasible.

PMID- 18073193
TI  - Small-scale extracts for the study of nucleotide excision repair and non
      homologous end joining.
AB  - The repair of DNA by nucleotide excision repair (NER) and non-homologous end
      joining (NHEJ) is essential for maintenance of genomic integrity and cell
      viability. Examination of NHEJ and NER in vitro using cell-free extracts has led
      to a deeper understanding of the biochemical mechanisms that underlie these
      processes. Current methods for production of whole-cell extracts (WCEs) to
      investigate NER and NHEJ start with one or more liters of culture containing 1-5
      x 10(9) cells. Here, we describe a small-scale method for production of WCE that
      can be used to study NER. We also describe a rapid, small-scale method for the
      preparation of WCE that can be used in the study of NHEJ. These methods require
      less time, 20- to 1000-fold fewer cells than large-scale extracts, facilitate
      examination of numerous samples and are ideal for such applications as the study
      of host-virus interactions and analysis of mutant cell lines.

PMID- 18073194
TI  - PlantTribes: a gene and gene family resource for comparative genomics in plants.
AB  - The PlantTribes database (http://fgp.huck.psu.edu/tribe.html) is a plant gene
      family database based on the inferred proteomes of five sequenced plant species:
      Arabidopsis thaliana, Carica papaya, Medicago truncatula, Oryza sativa and
      Populus trichocarpa. We used the graph-based clustering algorithm MCL [Van Dongen
      (Technical Report INS-R0010 2000) and Enright et al. (Nucleic Acids Res. 2002;
      30: 1575-1584)] to classify all of these species' protein-coding genes into
      putative gene families, called tribes, using three clustering stringencies (low,
      medium and high). For all tribes, we have generated protein and DNA alignments
      and maximum-likelihood phylogenetic trees. A parallel database of microarray
      experimental results is linked to the genes, which lets researchers identify
      groups of related genes and their expression patterns. Unified nomenclatures were
      developed, and tribes can be related to traditional gene families and conserved
      domain identifiers. SuperTribes, constructed through a second iteration of MCL
      clustering, connect distant, but potentially related gene clusters. The global
      classification of nearly 200 000 plant proteins was used as a scaffold for
      sorting approximately 4 million additional cDNA sequences from over 200 plant
      species. All data and analyses are accessible through a flexible interface
      allowing users to explore the classification, to place query sequences within the
      classification, and to download results for further study.

PMID- 18073195
TI  - Efficient siRNA selection using hybridization thermodynamics.
AB  - Small interfering RNA (siRNA) are widely used to infer gene function. Here,
      insights in the equilibrium of siRNA-target hybridization are used for selection
      of efficient siRNA. The accessibilities of siRNA and target mRNA for
      hybridization, as measured by folding free energy change, are shown to be
      significantly correlated with efficacy. For this study, a partition function
      calculation that considers all possible secondary structures is used to predict
      target site accessibility; a significant improvement over calculations that
      consider only the predicted lowest free energy structure or a set of low free
      energy structures. The predicted thermodynamic features, in addition to siRNA
      sequence features, are used as input for a support vector machine that selects
      functional siRNA. The method works well for predicting efficient siRNA (efficacy
      >70%) in a large siRNA data set from Novartis. The positive predictive value
      (percentage of sites predicted to be efficient for silencing that are) is as high
      as 87.6%. The sensitivity and specificity are 22.7 and 96.5%, respectively. When
      tested on data from different sources, the positive predictive value increased
      8.1% by adding equilibrium terms to 25 local sequence features. Prediction of
      hybridization affinity using partition functions is now available in the
      RNAstructure software package.

PMID- 18073196
TI  - Structure-function analysis of the RNA polymerase cleft loops elucidates initial
      transcription, DNA unwinding and RNA displacement.
AB  - The active center clefts of RNA polymerase (RNAP) from the archaeon Pyrococcus
      furiosus (Pfu) and of yeast RNAP II are nearly identical, including four
      protruding loops, the lid, rudder, fork 1 and fork 2. Here we present a structure
      function analysis of recombinant Pfu RNAP variants lacking these cleft loops, and
      analyze the function of each loop at different stages of the transcription cycle.
      All cleft loops except fork 1 were required for promoter-directed transcription
      and efficient elongation. Unprimed de novo transcription required fork 2, the lid
      was necessary for primed initial transcription. Analysis of templates containing
      a pre-melted bubble showed that rewinding of upstream DNA drives RNA separation
      from the template. During elongation, downstream DNA strand separation required
      template strand binding to an invariant arginine in switch 2, and apparently
      interaction of an invariant arginine in fork 2 with the non-template strand.

PMID- 18073197
TI  - Epstein-Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA
      polymerase BALF5.
AB  - MicroRNAs (miRNAs) have been implicated in sequence-specific cleavage,
      translational repression or deadenylation of specific target mRNAs resulting in
      post-transcriptional gene silencing. Epstein-Barr virus (EBV) encodes 23 miRNAs
      of unknown function. Here we show that the EBV-encoded miRNA miR-BART2 down
      regulates the viral DNA polymerase BALF5. MiR-BART2 guides cleavage within the 3'
      untranslated region (3'UTR) of BALF5 by virtue of its complete complementarity to
      its target. Induction of the lytic viral replication cycle results in a reduction
      of the level of miR-BART2 with a strong concomitant decrease of cleavage of the
      BALF5 3'UTR. Expression of miR-BART2 down-regulates the activity of a luciferase
      reporter gene containing the BALF5 3'UTR. Forced expression of miR-BART2 during
      lytic replication resulted in a 40-50% reduction of the level of BALF5 protein
      and a 20% reduction of the amount of virus released from EBV-infected cells. Our
      results are compatible with the notion that EBV-miR-BART2 inhibits transition
      from latent to lytic viral replication.

PMID- 18073198
TI  - Polony analysis of gene expression in ES cells and blastocysts.
AB  - Expression profiling of stem cells is challenging due to their small numbers and
      heterogeneity. The PCR colony (polony) approach has theoretical advantages as an
      assay for stem cells but has not been applied to small numbers of cells. An assay
      has been developed that is sensitive enough to detect mRNAs from small numbers of
      ES cells and from fractions of a single mouse blastocyst. Genes assayed include
      Oct3, Rex1, Nanog, Cdx2 and GLUT-1. The assay is highly sensitive so that
      multiple mRNAs from a single blastocyst were easily detected in the same assay.
      In its present version, the assay is an attractive alternative to conventional RT
      PCR for profiling small populations of stem cells. The assay is also amenable to
      improvements that will increase its sensitivity and ability to analyze many cDNAs
      simultaneously.

PMID- 18073199
TI  - Quantitative telomeric overhang determination using a double-strand specific
      nuclease.
AB  - Telomeres terminate in 3' overhangs that function in end protection and the
      formation of t-loops. Determining the steps and factors involved in overhang
      processing is compromised by the inability to easily and accurately determine
      overhang size in the presence of many kilobases of double-stranded telomeric DNA.
      We here describe the use of a double-strand specific nuclease (DSN) that entirely
      digests double-stranded DNA including telomeres, leaving the overhangs intact so
      that they can be measured.

PMID- 18073201
TI  - The oligomeric state of the active BM2 ion channel protein of influenza B virus.
AB  - Influenza A virus and influenza B virus particles both contain small integral
      membrane proteins (A/M2 and BM2, respectively) that function as a pH-sensitive
      proton channel and are essential for virus replication. The mechanism of action
      of the M2 channels is a subject of scientific interest particularly as A/M2
      channel was shown to be a target for the action of the antiviral drug amantadine.
      Unfortunately, an inhibitor of the BM2 channel activity is not known. Thus,
      knowledge of the structural and functional properties of the BM2 channel is
      essential for the development of potent antiviral drugs. The characterization of
      the oligomeric state of the BM2 channel is an essential first step in the
      understanding of channel function. Here we describe determination of the
      stoichiometry of the BM2 proton channel by utilizing three different approaches.
      1) We demonstrated that BM2 monomers can be chemically cross-linked to yield
      species consistent with dimers, trimers, and tetramers. 2) We studied
      electrophysiological and biochemical properties of mixed oligomers consisting of
      wild-type and mutated BM2 subunits and related these data to predicted binomial
      distribution models. 3) We used fluorescence resonance energy transfer (FRET) in
      combination with biochemical measurements to estimate the relationships between
      BM2 channel subunits expressed in the plasma membrane. Our experimental data are
      consistent with a tetrameric structure of the BM2 channel. Finally, we
      demonstrated that BM2 transmembrane domain is responsible for the channel
      oligomerization.

PMID- 18073200
TI  - Functional endogenous LINE-1 retrotransposons are expressed and mobilized in rat
      chloroleukemia cells.
AB  - LINE-1 (L1) is a highly successful autonomous non-LTR retrotransposon and a major
      force shaping mammalian genomes. Although there are about 600 000 L1 copies
      covering 23% of the rat genome, full-length rat L1s (L1Rn) with intact open
      reading frames (ORFs) representing functional master copies for
      retrotransposition have not been identified yet. In conjunction with studies to
      elucidate the role of L1 retrotransposons in tumorigenesis, we isolated and
      characterized 10 different cDNAs from transcribed full-length L1Rn elements in
      rat chloroleukemia (RCL) cells, each encoding intact ORF1 proteins (ORF1p). We
      identified the first functional L1Rn retrotransposon from this pool of cDNAs,
      determined its activity in HeLa cells and in the RCL cell line the cDNAs
      originated from and demonstrate that it is mobilized in the tumor cell line in
      which it is expressed. Furthermore, we generated monoclonal antibodies directed
      against L1Rn ORF1 and ORF2-encoded recombinant proteins, analyzed the expression
      of L1-encoded proteins and found ORF1p predominantly in the nucleus. Our results
      support the hypothesis that the reported explosive amplification of genomic L1Rn
      sequences after their transcriptional activation in RCL cells is based on L1
      retrotransposition. Therefore, L1 activity might be one cause for genomic
      instability observed during the progression of leukemia.

PMID- 18073202
TI  - Zinc deficiency-induced iron accumulation, a consequence of alterations in iron
      regulatory protein-binding activity, iron transporters, and iron storage
      proteins.
AB  - One consequence of zinc deficiency is an elevation in cell and tissue iron
      concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3
      cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S,
      50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture,
      cells in the D group were characterized by a 50% decrease in intracellular zinc
      and a 35% increase in intracellular iron relative to cells in the S and C groups.
      The increase in cellular iron was associated with increased transferrin receptor
      1 protein and mRNA levels and increased ferritin light chain expression. The
      divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased
      during zinc deficiency-induced iron accumulation. Examination of zinc-deficient
      cells revealed increased binding of iron regulatory protein 2 (IRP2) and
      decreased binding of IRP1 to a consensus iron-responsive element. The increased
      IRP2-binding activity in zinc-deficient cells coincided with an increased level
      of IRP2 protein. The accumulation of IRP2 protein was independent of zinc
      deficiency-induced intracellular nitric oxide production but was attenuated by
      the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium.
      These data support the concept that zinc deficiency can result in alterations in
      iron transporter, storage, and regulatory proteins, which facilitate iron
      accumulation.

PMID- 18073203
TI  - Cell surface-expressed cation-independent mannose 6-phosphate receptor (CD222)
      binds enzymatically active heparanase independently of mannose 6-phosphate to
      promote extracellular matrix degradation.
AB  - Heparanase is a beta-D-endoglucuronidase that cleaves heparan sulfate, an
      important structural component of the extracellular matrix (ECM) and vascular
      basement membrane (BM). The cleavage of heparan sulfate by heparanase-expressing
      cells, such as activated leukocytes, metastatic tumor cells, and proliferating
      endothelial cells, facilitates degradation of the ECM/BM to promote cell invasion
      associated with inflammation, tumor metastasis, and angiogenesis. In addition to
      its enzymatic function, heparanase has also recently been shown to act as a cell
      adhesion and/or signaling molecule upon interaction with cell surfaces. Despite
      the obvious importance of the mechanisms for the binding of heparanase to cell
      surfaces, the receptor(s) for heparanase remain poorly defined. In this study, we
      identify the 300-kDa cation-independent mannose 6-phosphate receptor (CIMPR) as a
      cell surface receptor for heparanase. Purified platelet heparanase was shown to
      bind the human CIMPR expressed on the surface of a transfected mouse L cell line.
      Optimal binding was determined to be at a slightly acidic pH (6.5-7.0) with
      heparanase remaining on the cell surface for up to 10 min at 37 degrees C. In
      contrast, mouse L cells or Chinese hamster ovary cells expressing the cation
      dependent mannose 6-phosphate receptor (CDMPR) showed no binding of heparanase.
      Interestingly, the binding of heparanase to CIMPR was independent of Man-6-P
      moieties. Significantly, primary human T cells upon activation were shown to
      dramatically up-regulate levels of cell surface-expressed CIMPR, which showed a
      concomitant increase in their capacity to bind heparanase. Furthermore, the
      tethering of heparanase to the surface of cells via CIMPR was found to increase
      their capacity to degrade an ECM or a reconstituted BM. These data suggest an
      important role for CIMPR in the cell surface presentation of enzymatically active
      heparanase for the efficient passage of T cells into an inflammatory site and
      have implications for the use of this mechanism by other cell types to enhance
      cell invasion.

PMID- 18073204
TI  - The tyrosine binding pocket in the adaptor protein 1 (AP-1) mu1 subunit is
      necessary for Nef to recruit AP-1 to the major histocompatibility complex class I
      cytoplasmic tail.
AB  - To evade the anti-human immunodeficiency virus (HIV) immune response, the HIV Nef
      protein disrupts major histocompatibility complex class I (MHC-I) trafficking by
      recruiting the clathrin adaptor protein 1 (AP-1) to the MHC-I cytoplasmic tail.
      Under normal conditions AP-1 binds dileucine and tyrosine signals (YXX phi
      motifs) via physically separate binding sites. In the case of the Nef-MHC-I
      complex, a tyrosine in the human leukocyte antigen (HLA)-A2 cytoplasmic tail
      ((320)YSQA) and a methionine in Nef (Met(20)) are absolutely required for AP-1
      binding. Also present in Nef is a dileucine motif, which does not normally affect
      MHC-I trafficking and is not needed to recruit AP-1 to the Nef-MHC-I-complex.
      However, evidence is presented here that this dileucine motif can be activated by
      fusing Nef to the HLA-A2 tail in cis. Thus, the inability of this motif to
      function in trans likely results from a structural change that occurs when Nef
      binds to the MHC-I cytoplasmic tail. The physiologically relevant tyrosine
      dependent recruitment of AP-1 to MHC-I, which occurs whether Nef is present in
      cis or trans, was stabilized by the acidic and polyproline domains within Nef.
      Additionally, amino acids Ala(324) and Asp(327) in the cytoplasmic tails of HLA-A
      and (but not HLA-C and HLA-E) molecules also stabilized AP-1 binding. Finally,
      mutation of the tyrosine binding pocket in the mu subunit of AP-1 created a
      dominant negative inhibitor of Nef-induced down-modulation of HLA-A2 that
      disrupted binding of wild type AP-1 to the Nef-MHC-I complex. Thus, these data
      provide evidence that Nef binding to the MHC-I cytoplasmic tail stabilizes the
      interaction of a tyrosine in the MHC-I cytoplasmic tail with the natural tyrosine
      binding pocket in AP-1.

PMID- 18073205
TI  - Structure-function analysis of the THAP zinc finger of THAP1, a large C2CH DNA
      binding module linked to Rb/E2F pathways.
AB  - THAP1, the founding member of a previously uncharacterized large family of
      cellular proteins (THAP proteins), is a sequence-specific DNA-binding factor that
      has recently been shown to regulate cell proliferation through modulation of
      pRb/E2F cell cycle target genes. THAP1 shares its DNA-binding THAP zinc finger
      domain with Drosophila P element transposase, zebrafish E2F6, and several
      nematode proteins interacting genetically with the retinoblastoma protein pRb. In
      this study, we report the three-dimensional structure and structure-function
      relationships of the THAP zinc finger of human THAP1. Deletion mutagenesis and
      multidimensional NMR spectroscopy revealed that the THAP domain of THAP1 is an
      atypical zinc finger of approximately 80 residues, distinguished by the presence
      between the C2CH zinc coordinating residues of a short antiparallel beta-sheet
      interspersed by a long loop-helix-loop insertion. Alanine scanning mutagenesis of
      this loop-helix-loop motif resulted in the identification of a number of critical
      residues for DNA recognition. NMR chemical shift perturbation analysis was used
      to further characterize the residues involved in DNA binding. The combination of
      the mutagenesis and NMR data allowed the mapping of the DNA binding interface of
      the THAP zinc finger to a highly positively charged area harboring multiple
      lysine and arginine residues. Together, these data represent the first structure
      function analysis of a functional THAP domain, with demonstrated sequence
      specific DNA binding activity. They also provide a structural framework for
      understanding DNA recognition by this atypical zinc finger, which defines a novel
      family of cellular factors linked to cell proliferation and pRb/E2F cell cycle
      pathways in humans, fish, and nematodes.

PMID- 18073206
TI  - Proximity and branch migration mechanisms in HIV-1 minus strand strong stop DNA
      transfer.
AB  - Human immunodeficiency virus type 1 minus strand transfer was measured using a
      genomic donor-acceptor template system in vitro. Donor RNA D199, having the
      minimum region required for minus strong stop DNA synthesis, was previously shown
      to transfer with 35% efficiency to an acceptor RNA representing the 3' repeat
      region. Donor D520, having an additional 321-nucleotide segment extending into
      gag, transferred at 75% efficiency. In this study each transfer step was analyzed
      to account for the difference. Measurement of terminal transfer indicated that
      the 3' terminus of the cDNA generated using D520 is more accessible for transfer
      than that of D199. Nevertheless, acceptor competition experiments demonstrated
      that D520 has a greater preference for invasion-driven versus terminal transfer
      than D199. Competition mapping showed that the base of the transactivation
      response element is the primary invasion site for D520, important for efficient
      acceptor invasion. Acceptors complementary to the invasion and terminal transfer
      sites, but not the region between, allowed assessment of the significance of
      hybrid propagation by branch migration. These bipartite acceptors showed that
      with D520, invasion raises the local concentration of the acceptor for efficient
      terminal transfer by a proximity effect. However, with D199, invasion is
      relatively inefficient, and the cDNA 3' terminus is not very accessible. For most
      transfers that occurred, the acceptor accessed the cDNA 3' end by branch
      migration. Results suggest that both proximity and branch migration mechanisms
      contribute to transfers, with the proportion determined by donor-cDNA structure.
      D520 transfers better because it has greater accessibility for both invasion and
      terminus transfer.

PMID- 18073207
TI  - c-Met must translocate to the nucleus to initiate calcium signals.
AB  - Hepatocyte growth factor (HGF) is important for cell proliferation,
      differentiation, and related activities. HGF acts through its receptor c-Met,
      which activates downstream signaling pathways. HGF binds to c-Met at the plasma
      membrane, where it is generally believed that c-Met signaling is initiated. Here
      we report that c-Met rapidly translocates to the nucleus upon stimulation with
      HGF. Ca(2+) signals that are induced by HGF result from phosphatidylinositol 4,5
      bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the
      nucleus rather than within the cytoplasm. Translocation of c-Met to the nucleus
      depends upon the adaptor protein Gab1 and importin beta1, and formation of Ca(2+)
      signals in turn depends upon this translocation. HGF may exert its particular
      effects on cells because it bypasses signaling pathways in the cytoplasm to
      directly activate signaling pathways in the nucleus.

PMID- 18073209
TI  - Structural heterogeneity of type I collagen triple helix and its role in
      osteogenesis imperfecta.
AB  - We investigated regions of different helical stability within human type I
      collagen and discussed their role in intermolecular interactions and osteogenesis
      imperfecta (OI). By differential scanning calorimetry and circular dichroism, we
      measured and mapped changes in the collagen melting temperature (DeltaTm) for 41
      different Gly substitutions from 47 OI patients. In contrast to peptides, we
      found no correlations of DeltaTm with the identity of the substituting residue.
      Instead, we observed regular variations in DeltaTm with the substitution location
      in different triple helix regions. To relate the DeltaTm map to peptide-based
      stability predictions, we extracted the activation energy of local helix
      unfolding (DeltaG) from the reported peptide data. We constructed the DeltaG map
      and tested it by measuring the H-D exchange rate for glycine NH residues involved
      in interchain hydrogen bonds. Based on the DeltaTm and DeltaG maps, we delineated
      regional variations in the collagen triple helix stability. Two large, flexible
      regions deduced from the DeltaTm map aligned with the regions important for
      collagen fibril assembly and ligand binding. One of these regions also aligned
      with a lethal region for Gly substitutions in the alpha1(I) chain.

PMID- 18073208
TI  - Structural requirements for multimerization of the pathogen receptor dendritic
      cell-specific ICAM3-grabbing non-integrin (CD209) on the cell surface.
AB  - The myeloid C-type lectin dendritic cell-specific ICAM3-grabbing non-integrin (DC
      SIGN, CD209) recognizes oligosaccharide ligands on clinically relevant pathogens
      (HIV, Mycobacterium, and Aspergillus). Alternative splicing and genomic
      polymorphism generate DC-SIGN mRNA variants, which have been detected at sites of
      pathogen entrance and transmission. We present evidence that DC-SIGN neck
      variants are expressed on dendritic and myeloid cells at the RNA and protein
      levels. Structural analysis revealed that multimerization of DC-SIGN within a
      cellular context depends on the lectin domain and the number and arrangement of
      the repeats within the neck region, whose glycosylation negatively affects
      oligomer formation. Naturally occurring DC-SIGN neck variants differ in
      multimerization competence in the cell membrane, exhibit altered sugar binding
      ability, and retain pathogen-interacting capacity, implying that pathogen-induced
      cluster formation predominates over the basal multimerization capability.
      Analysis of DC-SIGN neck polymorphisms indicated that the number of allelic
      variants is higher than previously thought and that multimerization of the
      prototypic molecule is modulated in the presence of allelic variants with a
      different neck structure. Our results demonstrate that the presence of allelic
      variants or a high level of expression of neck domain splicing isoforms might
      influence the presence and stability of DC-SIGN multimers on the cell surface,
      thus providing a molecular explanation for the correlation between DC-SIGN
      polymorphisms and altered susceptibility to HIV-1 and other pathogens.

PMID- 18073210
TI  - Differential coupling of M1 muscarinic and alpha7 nicotinic receptors to
      inhibition of pemphigus acantholysis.
AB  - The mechanisms mediating and regulating assembly and disassembly of intercellular
      junctions is a subject of intensive research. The IgG autoantibodies produced in
      patients with the immunoblistering skin disease pemphigus vulgaris (PV) can
      induce keratinocyte (KC) dyshesion (acantholysis) via mechanisms that involve
      signaling kinases targeting intercellular adhesion molecules, thus providing a
      useful model to study the physiologic regulation of KC cohesion. Previous studies
      showed that activation of Src and protein kinase C are the earliest events in the
      PV IgG-induced intracellular phosphorylation cascades and that cholinergic
      agonists are effective for treating patients with pemphigus. In this study, we
      sought to elucidate the molecular mechanisms allowing cholinergic agonists to
      inhibit PV IgG-induced acantholysis and phosphorylation of KC adhesion molecules.
      The extent of acantholysis in KC monolayers correlated closely with the degree of
      PV IgG-induced phosphorylation of p120- and beta-catenins, with classic isoforms
      of protein kinase C mediating serine phosphorylation of beta-catenin and Src
      tyrosine phosphorylation of p120-catenin. The M(1) muscarinic agonist pilocarpine
      blocked phosphorylation of both catenins, which could be abolised by the M(1)
      antagonist MT7. The alpha7 nicotinic agonist AR-R17779 inhibited phosphorylation
      of P120-cateinin. The alpha7 antagonist methyllycaconitine abolished the effect
      of AR-R17779. Okadaic acid abrogated protective effects of agonists on
      phosphorylation of beta-catenin, and pervanadate, on that of p120-catenin.
      Stimulation of KCs with pilocarpine significantly (p < 0.05) elevated both
      serine/threonine and tyrosine phosphatase activities in KCs. AR-R17779 both
      stimulated tyrosine phosphatase and decreased PV IgG-induced Src activity.
      Methyllycaconitine released Src activity in intact KCs and caused acantholysis.
      Thus, downstream signaling from M(1) abolished PV IgG-dependent catenin
      phosphorylation due to activation of both serine/threonine and tyrosine
      phosphatases, whereas alpha7 action involved both activation of tyrosine
      phosphatase and inhibition of Src. These findings identified novel paradigm of
      regulation of signaling kinases associated with cholinergic receptors and
      provided mechanistic explanation of therapeutic activity of cholinomimetics in PV
      patients.

PMID- 18073211
TI  - Conserved dimeric subunit stoichiometry of SLC26 multifunctional anion
      exchangers.
AB  - The SLC26 gene family encodes multifunctional transport proteins in numerous
      tissues and organs. Some paralogs function as anion exchangers, others as anion
      channels, and one, prestin (SLC26A5), represents a membrane-bound motor protein
      in outer hair cells of the inner ear. At present, little is known about the
      molecular basis of this functional diversity. We studied the subunit
      stoichiometry of one bacterial, one teleost, and two mammalian SLC26 isoforms
      expressed in Xenopus laevis oocytes or in mammalian cells using blue native PAGE
      and chemical cross-linking. All tested SLC26s are assembled as dimers composed of
      two identical subunits. Co-expression of two mutant prestins with distinct
      voltage-dependent capacitances results in motor proteins with novel electrical
      properties, indicating that the two subunits do not function independently. Our
      results indicate that an evolutionarily conserved dimeric quaternary structure
      represents the native and functional state of SLC26 transporters.

PMID- 18073212
TI  - Structural and biophysical analysis of the DNA binding properties of myelin
      transcription factor 1.
AB  - Zinc binding domains, or zinc fingers (ZnFs), form one of the most numerous and
      most diverse superclasses of protein structural motifs in eukaryotes. Although
      our understanding of the functions of several classes of these domains is
      relatively well developed, we know much less about the molecular mechanisms of
      action of many others. Myelin transcription factor 1 (MyT1) type ZnFs are found
      in organisms as diverse as nematodes and mammals and are found in a range of
      sequence contexts. MyT1, one of the early transcription factors expressed in the
      developing central nervous system, contains seven MyT1 ZnFs that are very highly
      conserved both within the protein and between species. We have used a range of
      biophysical techniques, including NMR spectroscopy and data-driven macromolecular
      docking, to investigate the structural basis for the interaction between MyT1
      ZnFs and DNA. Our data indicate that MyT1 ZnFs recognize the major groove of DNA
      in a way that appears to differ from other known zinc binding domains.

PMID- 18073213
TI  - A plant Ca2+ pump, ACA2, relieves salt hypersensitivity in yeast. Modulation of
      cytosolic calcium signature and activation of adaptive Na+ homeostasis.
AB  - Stress responses in both plants and yeast utilize calcium-mediated signaling. A
      yeast strain, K616, which lacks Ca(2+) pumps, requires micromolar Ca(2+) for
      growth. In medium containing 100 microM Ca(2+), K616 can withstand osmotic stress
      (750 mM sorbitol) and ionic stress (300 mM KCl) but not hypersodic stress (300 mM
      NaCl). Heterologous expression of the endoplasmic reticulum-located Arabidopsis
      thaliana Ca(2+)-ATPase, ACA2, permits K616 to grow under NaCl stress even in
      Ca(2+)-depleted medium. All stresses tested generated transient elevation of
      cytosolic Ca(2+) in wild type yeast, K601, whereas NaCl alone induced prolonged
      elevation of cytosolic Ca(2+) in K616. Both the Ca(2+) transient and survival of
      cultures subjected to NaCl stress was similar for the ACA2 transformant and K601.
      However, whereas K601 maintained low cytosolic Na(+) predominantly by pumping it
      out across the plasma membrane, the transformant sequestered Na(+) in internal
      organelles. This sequestration requires the presence of an endomembrane
      Na(+)/H(+)-antiporter, NHX1, which does not play a significant role in salt
      tolerance of wild type yeast except at acidic pH. Transcript levels of the plasma
      membrane Na(+)-ATPase, ENA1, were strongly induced only in K601, whereas NHX1 was
      strongly induced in both K601 and the ACA2 transformant. The calmodulin kinase
      inhibitor KN62 significantly reduced the salt tolerance of the ACA2 transformant
      and the transcriptional induction of NHX1. Thus, the heterologous expression of a
      plant endomembrane Ca(2+) pump results in the rapid depletion of cytosolic Ca(2+)
      and the activation of an alternate mechanism for surviving saline stress.

PMID- 18073214
TI  - ICER-1gamma overexpression drives palmitate-mediated connexin36 down-regulation
      in insulin-secreting cells.
AB  - Channels formed by the gap junction protein connexin36 (Cx36) contribute to the
      proper control of insulin secretion. We investigated the impact of chronic
      hyperlipidemia on Cx36 expression in pancreatic beta-cells. Prolonged exposure to
      the saturated free fatty acid palmitate reduced the expression of Cx36 in several
      insulin-secreting cell lines and isolated mouse islets. The effect of palmitate
      was fully blocked upon protein kinase A (PKA) inhibition by H89 and (Rp)-cAMP,
      indicating that the cAMP/PKA pathway is involved in the control of Cx36
      expression. Palmitate treatment led to overexpression of the inducible cAMP early
      repressor (ICER-1gamma), which bound to a functional cAMP-response element
      located in the promoter of the CX36 gene. Inhibition of ICER-1gamma
      overexpression prevented the Cx36 decrease, as well as the palmitate-induced beta
      cell secretory dysfunction. Finally, freshly isolated islets from mice undergoing
      a long term high fat diet expressed reduced Cx36 levels and increased ICER-1gamma
      levels. Taken together, these data demonstrate that chronic exposure to palmitate
      inhibits the Cx36 expression through PKA-mediated ICER-1gamma overexpression.
      This Cx36 down-regulation may contribute to the reduced glucose sensitivity and
      altered insulin secretion observed during the pre-diabetic stage and in the
      metabolic syndrome.

PMID- 18073216
TI  - Beta-2-glycoprotein 1-dependent macrophage uptake of apoptotic cells. Binding to
      lipoprotein receptor-related protein receptor family members.
AB  - The recognition and removal of apoptotic cells is critical to development, tissue
      homeostasis, and the resolution of inflammation. Many studies have shown that
      phagocytosis is regulated by signaling mechanisms that involve distinct ligand
      receptor interactions that drive the engulfment of apoptotic cells. Studies from
      our laboratory have shown that the plasma protein beta-2-glycoprotein 1
      (beta2GP1), a member of the short consensus repeat superfamily, binds
      phosphatidylserine-containing vesicles and apoptotic cells and promotes their
      bridging and subsequent engulfment by phagocytes. The phagocyte receptor for the
      protein/apoptotic cell complex, however, is unknown. Here we report that a member
      of the low density lipoprotein receptor-related protein family on phagocytes
      binds and facilitates engulfment of beta2GP1-phosphatidylserine and beta2GP1
      apoptotic cell complexes. Using recombinant beta2GP1, we also show that beta2GP1
      dependent uptake is mediated by bridging of the target cell to the phagocyte
      through the protein C- and N-terminal domains, respectively.

PMID- 18073215
TI  - Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the
      death stimulus.
AB  - Macroautophagy has been implicated as a mechanism of cell death. However, the
      relationship between this degradative pathway and cell death is unclear as
      macroautophagy has been shown recently to protect against apoptosis. To better
      define the interplay between these two critical cellular processes, we determined
      whether inhibition of macroautophagy could have both pro-apoptotic and anti
      apoptotic effects in the same cell. Embryonic fibroblasts from mice with a knock
      out of the essential macroautophagy gene atg5 were treated with activators of the
      extrinsic and intrinsic death pathways. Loss of macroautophagy sensitized these
      cells to caspase-dependent apoptosis from the death receptor ligands Fas and
      tumor necrosis factor-alpha (TNF-alpha). Atg5-/- mouse embryonic fibroblasts had
      increased activation of the mitochondrial death pathway in response to Fas/TNF
      alpha in concert with decreased ATP levels. Fas/TNF-alpha treatment failed to up
      regulate macroautophagy, and in fact, decreased activity at late time points. In
      contrast to their sensitization to Fas/TNF-alpha, Atg5-/- cells were resistant to
      death from menadione and UV light. In the absence of macroautophagy, an up
      regulation of chaperone-mediated autophagy induced resistance to these stressors.
      These results demonstrate that inhibition of macroautophagy can promote or
      prevent apoptosis in the same cell and that the response is governed by the
      nature of the death stimulus and compensatory changes in other forms of
      autophagy. Experimental findings that an inhibition of macroautophagy blocks
      apoptosis do not prove that autophagy mediates cell death as this effect may
      result from the protective up-regulation of other autophagic pathways such as
      chaperone-mediated autophagy.

PMID- 18073217
TI  - Phosphoinositide lipid phosphatases: natural regulators of phosphoinositide 3
      kinase signaling in T lymphocytes.
AB  - The phosphoinositide 3-kinase signaling pathway has been implicated in a range of
      T lymphocyte cellular functions, particularly growth, proliferation, cytokine
      secretion, and survival. Dysregulation of phosphoinositide 3-kinase-dependent
      signaling and function in leukocytes, including B and T lymphocytes, has been
      implicated in many inflammatory and autoimmune diseases. As befits a pivotal
      signaling cascade, several mechanisms exist to ensure that the pathway is tightly
      regulated. This minireview focuses on two lipid phosphatases, viz. the 3'
      phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10) and
      SHIP (Src homology 2 domain-containing inositol-5-phosphatase). We discuss their
      role in regulating T lymphocyte signaling as well their potential as future
      therapeutic targets.

PMID- 18073220
TI  - Opioids, pain, and fear.

PMID- 18073219
TI  - Chlamydia-psittaci-eradicating antibiotic therapy in patients with advanced-stage
      ocular adnexal MALT lymphoma.

PMID- 18073218
TI  - Myocyte enhancer factor 2A is transcriptionally autoregulated.
AB  - MEF2 (myocyte enhancer factor 2) proteins are a small family of transcription
      factors that play pivotal roles in striated muscle differentiation, development,
      and metabolism, in neuron survival and synaptic formation, and in lymphocyte
      selection and activation. Products of the four mammalian MEF2 genes, MEF2A,
      MEF2B, MEF2C, and MEF2D, are expressed with overlapping but distinct
      temporospatial patterns. Toward analysis of MEF2A functions and the determinants
      of its regulated expression, we have mapped and begun studies of the
      transcriptional control regions of this gene. Heterogeneous 5'-untranslated
      regions of MEF2A mRNAs result from use of alternative promoters and splicing
      patterns. The two closely approximated TATA-less promoters are approximately 65
      kb upstream of the exon containing the sole initiation codon. Ribonuclease
      protection and primer extension assays show that each promoter is active in
      various adult tissues. A canonical MEF2 site overlies the major promoter 1
      transcription start site. This element specifically binds MEF2 factors, including
      endogenous nuclear MEF2A according to chromatin immunoprecipitation studies, and
      is critical to MEF2A transcription in myocytes. The site exerts reciprocal
      control of the alternative promoters, silencing promoter 1 and activating
      promoter 2 under some conditions. Erk5 and p38 MAPK signaling stimulate MEF2A
      expression by activating both promoters from the MEF2 element. MEF2A
      transcription is therefore subject to positive or negative regulation by its
      protein products, depending on signaling activities that influence MEF2 factor
      trans-activity. The sole MEF2 gene of the cephalochordate amphioxus has a similar
      regulatory region structure, suggesting that this mode of autoregulatory control
      is conserved among higher metazoan MEF2 genes.

PMID- 18073221
TI  - First-line single-agent cetuximab in patients with advanced colorectal cancer.
AB  - BACKGROUND: The anti-epidermal growth factor receptor (EGFR) antibody cetuximab
      is active in heavily pretreated patients with metastatic colorectal cancer (mCRC)
      both in monotherapy and in combination with chemotherapy (CT). This study
      assesses the antitumor activity of single-agent cetuximab in CT-naive patients.
      PATIENTS AND METHODS: Phase II clinical trial was used. Patients were EGFR
      positive by immunohistochemistry and were not candidate for radical surgery, even
      in the case of substantial tumor shrinkage. Cetuximab was administered weekly.
      RESULTS: Thirty-nine patients were treated and evaluated. The most common adverse
      event was skin toxicity (89% any grade; 48% grade 1; 31% grade 2; 10% grade 3).
      One patient had a complete response and three obtained partial responses (10%
      overall response rate). Thirteen patients had stable disease (34%). Twenty-two
      patients experienced progressive disease (56%). Overall median time to
      progression (TTP) was 2 months, and the responders individual TTP was 12, 9, 9,
      and 6 months. CONCLUSIONS: Even in chemo-naive patients, cetuximab as single
      agent is active only in a small fraction of mCRC, similarly to what has been
      reported for heavily pretreated patients. The extent of benefit when response
      occurs is, however, such that it is mandatory to intensify the search for the
      predictive markers of response to cetuximab therapy.

PMID- 18073222
TI  - Opioid analgesics for cancer pain: symptom control for the living or comfort for
      the dying? A qualitative study to investigate the factors influencing the
      decision to accept morphine for pain caused by cancer.
AB  - BACKGROUND: Morphine and other opioids are the mainstay of cancer pain
      management, yet considerable fears surrounding them present barriers to pain
      control. Research in groups already using opioids has examined their concerns,
      but there is little evidence about how patients react when first offered opioids.
      We explored the factors influencing the decision to accept or reject morphine
      when first offered to patients with cancer. PATIENTS AND METHODS: A qualitative
      in-depth interview study nested within a cancer pain management trial. Interviews
      were conducted with 18 patients (nine females), aged 42-88 years. RESULTS: The
      categories that surrounded decisions about commencement of opioids were:
      anticipation of death; morphine as a last resort; the role of the professional;
      and 'no choice' but to commence. Participants rejected morphine as a medical
      intervention to control pain and promote quality of life because they saw it only
      as a comfort measure for the dying. However, opioids were more acceptable if
      health care providers had confidence in opioids and side-effects were well
      managed. CONCLUSION: Among cancer patients the idea that opioids represent a
      comfort measure for the dying and not legitimate analgesics may represent a
      greater barrier to their uptake than concerns about tolerance or addiction.

PMID- 18073223
TI  - Isolation and characterization of anti-FcgammaRIII (CD16) llama single-domain
      antibodies that activate natural killer cells.
AB  - FcgammaRIII (CD16) plays an important role in the anti-tumor effects of
      therapeutic antibodies. Bi-specific antibodies (bsAbs) targeting FcgammaRIII
      represent a powerful alternative to the recruitment of the receptor via the Fc
      fragment, but are not efficiently produced. Single-domain antibodies (sdAbs)
      endowed with many valuable structural features might help to bypass this problem.
      In the present work, we have isolated anti-FcgammaRIII sdAbs (C21 and C28) from a
      phage library generated from a llama immunized with FcgammaRIIIB extra-cellular
      domains. These sdAbs bind FcgammaRIIIA+ NK cells and FcgammaRIIIB+
      polymorphonuclear cells, but not FcgammaRI+ or FcgammaRII+ cells, as detected by
      indirect immunofluorescence. Competition experiments showed that C21 and C28
      sdAbs bind different FcgammaRIII epitopes, with C21 recognizing a linear and C28
      a conformational epitope of the receptor. Surface plasmon resonance experiments
      showed that C21 and C28 sdAbs bind FcgammaRIII with a K(D) in the 10 and 80 nM
      range, respectively. Importantly, the engagement by both molecules of
      FcgammaRIIIA expressed by transfected Jurkat T cells or by NK cells derived from
      peripheral blood induced a strong IL-2 and IFN-gamma production, respectively.
      These anti-FcgammaRIII sdAbs represent versatile tools for generating bsAbs under
      various formats, able to recruit FcgammaRIII killer cells to target and destroy
      tumor cells.

PMID- 18073224
TI  - Expression and enzymatic characterization of the soluble recombinant plasmepsin I
      from Plasmodium falciparum.
AB  - The plasmepsins are involved in the degradation of host cell hemoglobin during
      malaria infection. Plasmepsin I (PM I) initiates the degradative process, and has
      been suggested as an attractive target for the treatment of malaria. The
      production of active recombinant PM I, however, has been challenging. We report
      for the first time, the expression and partial characterization of soluble
      recombinant PM I from Plasmodium falciparum in which a truncated form of PM I
      (Lys77P-Leu329) (P indicates a propart residues) was fused to thioredoxin in the
      pET32b(+) vector, Trx-tPM I and expressed in Escherichia coli Rosetta-gami B
      (DE3)pLysS. The soluble fusion protein was purified from cell culture using a
      combination of Ni(2+) affinity and gel filtration chromatography and was capable
      of autocatalytic activation at pH 4.0-5.5, which occurred at Leu116P-Ser117P,
      seven residues upstream of the native cleavage site (Gly123P-Asn1). The mature
      tPM I (mtPM I) was capable of hydrolyzing both human hemoglobin with a pH optimum
      of pH 2.8-4.0 and the synthetic fluorogenic peptide EDANS-CO-CH(2)-CH(2)-CO
      ALERMFLSFP-Dap(DABCYL)-OH with a dual pH optima of pH 2.5-3.0 and pH 4.5-5.5.
      Using the synthetic substrate, mtPM I exhibited kinetic parameters comparable to
      native PM I.

PMID- 18073225
TI  - The state of regional health information organizations: current activities and
      financing.
AB  - Electronic clinical data exchange promises substantial financial and societal
      benefits, but it is unclear whether and when it will become widespread. In early
      2007 we surveyed 145 regional health information organizations (RHIOs), the U.S.
      entities working to establish data exchange. Nearly one in four was likely
      defunct. Only twenty efforts were of at least modest size and exchanging clinical
      data. Most early successes involved the exchange of test results. To support
      themselves, thirteen RHIOs received regular fees from participating
      organizations, and eight were heavily dependent on grants. Our findings raise
      concerns about the ability of the current approach to achieve widespread
      electronic clinical data exchange.

PMID- 18073226
TI  - A placebo controlled, dose-ranging, safety study of allogenic mesenchymal stem
      cells injected by endomyocardial delivery after an acute myocardial infarction.
AB  - AIMS: Although mesenchymal stem cells (MSCs) show promising signs in reducing
      myocardial infarct (MI) size, the safety of endomyocardial delivery and the most
      efficacious dose is unknown. METHODS AND RESULTS: Three days after MI, female
      Yorkshire swine (25-32 kg, age 2 months, n = 32) were randomized to
      endomyocardial delivery of one of three MSC doses (2.4 x 10(7), 2.4 x 10(8), 4.4
      x 10(8) cells) or vehicle control. Animals were sacrificed at 12 weeks. There
      were no safety issues related to cell delivery and all animals tolerated the
      procedure. By magnetic resonance imaging infarct size (g) was decreased in the
      experimental groups and increased in the control group; 2.4 x 10(7): Delta -2.5
      +/- 2.5 g, 2.4 x 10(8): -0.9 +/- 2.71 g, 4.4 x 10(8): -1.6 +/- 5.8 g, and control
      +3.6 +/- 3.4 g (P = 0.002, P = 0.016, and P = 0.055 compared with control,
      respectively). There was no effect on ejection fraction or left ventricular
      volumes. By histology there were no toxic effects of MSC delivery, however, few
      engrafted MSCs were observed. CONCLUSION: Direct MSC delivery into infarcted
      myocardium was safe and produced a local but not a functional effect. There was
      no dose-dependent effect. The effect of MSCs on infarct reduction may result from
      transient residence and subsequent paracrine effects.

PMID- 18073227
TI  - Arterial aneurysm in tuberous sclerosis.

PMID- 18073228
TI  - Bronchopericardial fistula, an unusual complication of oxytetracycline sclerosis
      therapy.
AB  - Here we report a rare case of bronchopericardial fistula following
      intrapericardial instillation of oxytetracycline. A 63-year-old female patient
      was admitted for management of malignant pericardial effusion secondary to right
      sided bronchogenic carcinoma. Medical therapy and recurrent percutaneous catheter
      drainage failed in resolving the problem, so subxiphoid pericardiostomy and
      drainage tube insertion was performed. There was no decrease in the drainage so
      we decided to perform pericardial sclerosis by intrapericardial tetracycline
      instillation. After the second time oxytetracycline instillation, the patient
      developed respiratory arrest with hemodynamic instability. A huge amount of
      yellow frothy secretion aspirated through the endotracheal tube. The presence of
      tetracycline in the bronchial secretion was proved by microbiological methods.
      The hemodynamic status of the patient deteriorated rapidly and despite all
      resuscitation measures we lost the patient within a few hours.

PMID- 18073229
TI  - Tuberculous tracheobronchial stricture causing post-pneumonectomy-like syndrome
      corrected by insertion of a bespoke Dumon stent.
AB  - Post-pneumonectomy syndrome is a well-recognised but uncommon late complication
      of pneumonectomy. Usually occurring after right-sided surgery, the mediastinal
      contents are rotated and displaced into the right hemithorax, producing airways
      or oesophageal compression. We report a case in which the radiological features
      and symptoms of post-pneumonectomy syndrome appeared to be precipitated by the
      development of a complex tuberculous tracheobronchial stenosis that resolved
      after the insertion of a bespoke Dumon stent.

PMID- 18073230
TI  - CABAS: a freely available PC program for fitting calibration curves in chromosome
      aberration dosimetry.
AB  - The aim of biological dosimetry is to estimate the dose and the associated
      uncertainty to which an accident victim was exposed. This process requires the
      use of the maximum-likelihood method for fitting a calibration curve, a procedure
      that is not implemented in most statistical computer programs. Several
      laboratories have produced their own programs, but these are frequently not user
      friendly and not available to outside users. We developed a software for fitting
      a linear-quadratic dose-response relationship by the method of maximum-likelihood
      and for estimating a dose from the number of aberrations observed. The program
      called as CABAS consists of the main curve-fitting and dose estimating module and
      modules for calculating the dose in cases of partial body exposure, for
      estimating the minimum number of cells necessary to detect a given dose of
      radiation and for calculating the dose in the case of a protracted exposure. The
      program is freely available at http://www.pu.kielce.pl/ibiol/cabas.

PMID- 18073231
TI  - Symptoms of sleep apnea and polysomnography as predictors of poor quality of life
      in overweight children and adolescents.
AB  - OBJECTIVE: The goal of this study was to examine the relationship between quality
      of life (QOL) and symptoms of obstructive sleep apnea (OSA) as well as
      objectively measured severity of OSA using polysomnography (PSG) in a cohort of
      overweight and at risk for overweight children and adolescents. METHODS: One
      hundred and fifty-one overweight subjects [90 males, average ages of 12.52, mean
      body mass index (BMI) Z-score of 2.27) and their parent/guardian completed
      surveys assessing QOL and symptoms of OSA syndrome. The subjects also underwent
      overnight PSG. RESULTS: Overweight patients reported poor QOL. Polysomnographic
      variables did not correlate with QOL. However, symptoms of OSA as reported on the
      Pediatric Sleep Questionnaire significantly correlated with QOL from both the
      parent and the subject. CONCLUSIONS: Overweight youth with symptoms of OSA have a
      lower QOL both by their report and parental report. Interestingly, objective
      measures of OSA did not correlate with QOL.

PMID- 18073232
TI  - Brief report: weight dissatisfaction, weight status, and weight loss in Mexican
      American children.
AB  - OBJECTIVE: To assess the association between weight dissatisfaction, weight
      status, and weight loss in Mexican-American children participating in a weight
      management program. METHODS: Participants included 265 Mexican American children
      recruited for a school-based weight management program. All children completed
      baseline assessments and changes in standardized body mass index (zBMI) were
      monitored in at-risk for overweight and overweight children (i.e., > 85th BMI
      percentile) who had been randomized to receive the weight loss intervention (n =
      101). RESULTS: Participants classified as at-risk for overweight or overweight
      reported greater weight dissatisfaction than normal weight children. Lower weight
      dissatisfaction at baseline was associated with greater changes in zBMI at 6
      months. Weight dissatisfaction did not change across the course of treatment.
      CONCLUSIONS: Mexican-American children whose weight status is greater than normal
      have greater weight dissatisfaction. Children with greater weight dissatisfaction
      are less likely to lose weight in a weight management program and weight
      dissatisfaction remains stable over the course of treatment.

PMID- 18073233
TI  - Identifying the classics: an examination of articles published in the Journal of
      Pediatric Psychology from 1976-2006.
AB  - OBJECTIVES: The purpose of the present investigation was to identify the top 100
      most highly cited "classic" articles in the Journal of Pediatric Psychology, from
      1976 to 2006. METHODS: The Cited Reference search option of the Web of Science(R)
      was used, which allows for identification of variations in citations. RESULTS:
      One-hundred and four classic articles ranging in citations from 46 to 192 (M =
      71.66, SD = 31.15) were identified. These articles were found to be mostly
      applied research that focused predominantly on children across several age groups
      with chronic illness. Citation trends among the classics revealed an inverted-u
      shape relationship between year since publication and citations per year, which
      peaked around seven years after publication. CONCLUSIONS: The current findings
      highlight some of the influential works in the field, which have contributed to
      important advances not only the field of pediatric psychology but other fields as
      well.

PMID- 18073234
TI  - Polysomnography and self-reported sleep, pain, fatigue, and anxiety in children
      with active and inactive juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To compare polysomnography (PSG) and self-reported sleep, symptoms
      (pain and fatigue), and anxiety between children with active and inactive
      juvenile rheumatoid arthritis (JRA) and examine relations among sleep, symptoms,
      and anxiety. METHODS: Two consecutive nights of PSG, self-reported sleep, and
      symptoms were obtained in 70 children 6-11 years of age with active (n = 35) or
      inactive (n = 35) JRA. RESULTS: On the second (study) night, PSG and self
      reported sleep variables were not different, but pain and fatigue were
      significantly higher (both p <.02) in children with active compared to inactive
      disease. In a stepwise regression, age, medications, disease status, anxiety,
      evening pain, total sleep time, and arousals explained 36% of the variance in
      fatigue and age, disease status, and evening pain were significant (all p <.04)
      predictors of fatigue. All children showed longer sleep latency and reduced sleep
      efficiency on the first night in the laboratory. CONCLUSIONS: Sleep was not
      altered in children with active JRA, however, the "first night effect" suggests
      that valid laboratory sleep assessments require an adaptation night.

PMID- 18073236
TI  - Journal of Pediatric Psychology (JPP), 2003 2007: Editor's Vale Dictum.

PMID- 18073237
TI  - "Quantal" Ca2+ release at the cytoplasmic aspect of the Ins(1,4,5)P3R channel in
      smooth muscle.
AB  - Smooth muscle responds to activation of the inositol (1,4,5)-trisphosphate
      receptor [Ins(1,4,5)P(3)R] with a graded concentration-dependent ("quantal") Ca2+
      release from the sarcoplasmic reticulum (SR) store. Graded release seems
      incompatible both with the finite capacity of the store and the Ca2+-induced Ca2+
      release (CICR)-like facility, at Ins(1,4,5)P3Rs, that, once activated, should
      release the entire content of SR Ca2+. The structural organization of the SR and
      the regulation of Ins(1,4,5)P3R activity by inositol (1,4,5)-trisphosphate
      [Ins(1,4,5)P3] and Ca2+ have each been proposed to explain ;quantal' Ca2+
      release. Here, we propose that regulation of Ins(1,4,5)P3R activity by lumenal
      Ca2+ acting at the cytoplasmic aspect of the receptor might explain ;quantal'
      Ca2+ release in smooth muscle. The entire SR store was found to be lumenally
      continuous and Ca2+ could diffuse freely throughout: peculiarities of SR
      structure are unlikely to account for ;quantal' release. While Ca2+ release was
      regulated by [Ca2+] within the SR, the velocity of release increased
      (accelerated) during the release process. The extent of acceleration of release
      determined the peak cytoplasmic [Ca2+] and was attenuated by a reduction in SR
      [Ca2+] or an increase in cytoplasmic Ca2+ buffering. Positive feedback by
      released Ca2+ acting at the cytoplasmic aspect of Ins(1,4,5)P3Rs (i.e. CICR-like)
      might (a) account for the acceleration, (b) provide the regulation of release by
      SR [Ca2+] and (c) explain the ;quantal' release process itself. During Ca2+
      release, SR [Ca2+] and thus unitary Ins(1,4,5)P3R currents decline, CICR reduces
      and stops. With increasing [Ins(1,4,5)P3], coincidental activation of several
      neighbouring Ins(1,4,5)P3Rs offsets the reduced Ins(1,4,5)P3R current to renew
      CICR and Ca2+ release.

PMID- 18073235
TI  - Symptoms of posttraumatic stress in parents of children with cancer: are they
      elevated relative to parents of healthy children?
AB  - OBJECTIVE: To examine posttraumatic stress symptoms (PTSS) in parents of children
      with cancer as a function of time since diagnosis, treatment status, and relapse
      history, and as compared to parents of healthy children. METHOD: Participants
      included parents of 199 children with cancer, comprising a cross-sectional sample
      of diagnoses and treatment phases, ranging from currently on therapy to long-term
      survivors, and 108 parents of healthy children obtained via acquaintance control
      methods. Parents completed a standardized self-report measure of PTSS. RESULTS:
      Within the cancer group, parental report of PTSS differed as a function of
      treatment status and time since diagnosis. Parents of children on active
      treatment endorsed similar levels of PTSS as control parents, whereas parents of
      children off treatment reported significantly lower levels of PTSS than did
      controls. Similarly, parents of long-term survivors reported significantly lower
      levels of PTSS than did controls, while parents of recently diagnosed children
      did not differ from controls on PTSS. In contrast, parents of children who had
      suffered a relapse reported significantly higher levels of PTSS, and were much
      more likely to be identified as a posttraumatic stress disorder (PTSD) case.
      CONCLUSIONS: As a group, parents of children with cancer did not demonstrate any
      evidence of increased PTSS relative to parents of healthy children. Time since
      diagnosis, child treatment status, and relapse history are significant
      determinants of parent PTSS. Only parents of children who experienced a relapse
      appear to be at increased risk of PTSD. The current results appear discrepant
      from the existing literature, and possible explanations for these discrepancies
      are examined.

PMID- 18073238
TI  - The role of cGMP and the rear of the cell in Dictyostelium chemotaxis and cell
      streaming.
AB  - During chemotaxis, pseudopod extensions lead the cell towards the source of
      attractant. The role of actin-filled pseudopodia at the front of the cell is well
      recognized, whereas the function of the rear of the cell in chemotaxis and cell
      cell interactions is less well known. Dictyostelium cell aggregation is mediated
      by outwardly propagating waves of extracellular cAMP that induce chemotaxis and
      cell-cell contacts, resulting in streams of cells moving towards the aggregation
      centre. Wild-type cells efficiently retract pseudopodia in the rear of the cell
      during the rising flank of the cAMP wave and have a quiescent cell posterior.
      This polarization largely remains during the declining flank, which causes cells
      to continue their chemotactic movement towards the aggregation centre and to form
      stable streams of moving cells. The dominance of the leading-edge pseudopod
      rescues chemotaxis during the rising flank of the wave, but the cells move in
      random directions after the peak of the wave has passed. As a consequence, cell
      cell contacts cannot be maintained, and the cell streams break up. The results
      show that a quiescent rear of the cell increases the efficiency of directional
      movement and is essential to maintain stable cell-cell contacts.

PMID- 18073239
TI  - The mitochondrial membrane potential and Ca2+ oscillations in smooth muscle.
AB  - Ca2+ uptake by mitochondria might both modulate the cytosolic Ca2+ concentration
      ([Ca2+]c) and depolarize the mitochondrial membrane potential (delta Psi m) to
      limit ATP production. To investigate how physiological Ca2+ signaling might
      affect energy production, delta Psi m was examined during Ca2+ oscillations in
      smooth muscle cells. In single, voltage-clamped smooth muscle cells, inhibition
      of mitochondrial Ca2+ accumulation inhibited inositol (1,4,5)-trisphosphate
      [Ins(1,4,5)P3]-evoked Ca2+ release and prolonged the time required for
      restoration of [Ca2+]c following activation of plasmalemmal Ca2+ currents (ICa).
      Ca2+ could be released from mitochondria immediately (within 15 seconds) after a
      [Ca2+]c rise evoked by Ins(1,4,5)P3 or ICa. Despite this evidence of
      mitochondrial Ca2+ accumulation, no change in delta Psi m was observed during
      single or repetitive [Ca2+]c oscillations evoked by these conditions.
      Occasionally, spontaneous, repetitive, persistent Ca 2+ oscillations were
      observed. In these cases, mitochondria displayed stochastic delta Psi m
      depolarizations, which were independent both of events in neighboring
      mitochondria and of the timing of the [Ca 2+]c oscillations themselves. Such
      delta Psi m depolarizations could be mimicked by increased exposure to either
      fluorescence excitation light or the delta Psi m-sensitive dye
      tetramethylrhodamine ethyl ester (TMRE) and were inhibited by antioxidants
      (ascorbic acid, catalase, Trolox and TEMPO) or the mitochondrial permeability
      transition pore (mPTP)-inhibitor cyclosporin A (CsA). Individual mitochondria
      within smooth muscle cells might depolarize during repetitive Ca2+ oscillations
      or during oxidative stress but not during the course of single [Ca2+]c transients
      evoked by Ca2+ influx or store release.

PMID- 18073240
TI  - Conservation of the pro-apoptotic nuclease activity of endonuclease G in
      unicellular trypanosomatid parasites.
AB  - Endonuclease G is a mitochondrial protein implicated in DNA fragmentation during
      apoptosis in cell types ranging from fungi to mammals. Features of programmed
      cell death have been reported in a number of single-celled organisms, including
      the human trypanosomatid parasites Leishmania and Trypanosoma. However, the
      protozoan cell death pathways and the effector molecules involved in such
      processes remain to be identified. In this report, we describe the pro-apoptotic
      function of endonuclease G in trypanosomatid parasites. Similar to metazoans,
      trypanosome endoG showed intrinsic nuclease activity, is localized in
      mitochondria and is released from this organelle when cell death is triggered.
      Overexpression of endoG strongly promoted apoptotic cell death under oxidant or
      differentiation-related stress in Leishmania and, conversely, loss of endoG
      expression conferred robust resistance to oxidant-induced cell death in T.
      brucei. These data demonstrate the conservation of the pro-apoptotic endonuclease
      activity of endoG in these evolutionarily ancient eukaryotic organisms.
      Furthermore, nuclear DNA degradation by endoG upon release from mitochondria
      might represent a caspase-independent cell death mechanism in trypanosomatid
      parasites as genes encoding caspase-like proteins have not been identified in
      their genomes.

PMID- 18073241
TI  - A model for the self-organization of exit sites in the endoplasmic reticulum.
AB  - Exit sites (ES) are specialized domains of the endoplasmic reticulum (ER) at
      which cargo proteins of the secretory pathway are packaged into COPII-coated
      vesicles. Although the essential COPII proteins (Sar1p, Sec23p-Sec24p, Sec13p
      Sec31p) have been characterized in detail and their sequential binding kinetics
      at ER membranes have been quantified, the basic processes that govern the self
      assembly and spatial organization of ERES have remained elusive. Here, we have
      formulated a generic computational model that describes the process of formation
      of ERES on a mesoscopic scale. The model predicts that ERES are arranged in a
      quasi-crystalline pattern, while their size strongly depends on the cargo
      modulated kinetics of COPII turnover - that is, a lack of cargo leads to smaller
      and more mobile ERES. These predictions are in favorable agreement with
      experimental data obtained by fluorescence microscopy. The model further suggests
      that cooperative binding of COPII components, for example mediated by regulatory
      proteins, is a key factor for the experimentally observed organism-specific ERES
      pattern. Moreover, the anterograde secretory flux is predicted to grow when the
      average size of ERES is increased, whereas an increase in the number of (small)
      ERES only slightly alters the flux.

PMID- 18073242
TI  - Spectrin-anchored phosphodiesterase 4D4 restricts cAMP from disrupting
      microtubules and inducing endothelial cell gap formation.
AB  - Dynamic cAMP fluctuations that are restricted to a sub-plasma-membrane domain
      strengthen endothelial barrier integrity. Phosphodiesterases (PDEs) localize
      within this domain where they limit cAMP diffusion into the bulk cytosolic
      compartment; however, the molecular identity of PDEs responsible for endothelial
      cell membrane cAMP compartmentation remain poorly understood. Our present
      findings reveal that the D4 splice variant of the PDE4 phosphodiesterase family -
      PDE4D4 - is expressed in pulmonary microvascular endothelial cells, and is found
      in plasma membrane fractions. PDE4D4 interacts with alpha II spectrin within this
      membrane domain. Although constitutive PDE4D4 activity limits cAMP access to the
      bulk cytosol, inhibiting its activity permits cAMP to access a cytosolic domain
      that is rich in microtubules, where it promotes protein kinase A (PKA)
      phosphorylation of tau at Ser214. Such phosphorylation reorganizes microtubules
      and induces interendothelial cell gap formation. Thus, spectrin-anchored PDE4D4
      shapes the physiological response to cAMP by directing it to barrier-enhancing
      effectors while limiting PKA-mediated microtubule reorganization.

PMID- 18073244
TI  - Menopause and the virtuous woman: the importance of the moral order in accounting
      for medical decision making.
AB  - Whether or not to use hormone replacement therapy (HRT) around the time of
      menopause is seen as an important decision for many mid-aged women. Recent
      studies of information provided to women to assist them in making a medical
      decision about the use of HRT have highlighted the importance of understanding
      the broader social context of the decision. In this article we examine one
      important aspect of western mid-aged women's social world: the moral order and
      the imperative of virtue. Qualitative data from a survey, focus group
      discussions, and interviews with mid-aged women about HRT use are used to provide
      examples of the importance of the local moral order in women's talk about
      menopause and HRT use. The implications of these data will be discussed in terms
      of the different narrative resources available to construct menopause and HRT,
      the role of morality, and the demonstration of virtue in daily social life,
      including medical decision making.

PMID- 18073245
TI  - Disciplining death: hypertension management and the production of mortal
      subjectivities.
AB  - Medicine powerfully mediates the relationship between life and death. This
      article argues that in the name of health, modern medicine constitutes a
      pathological mortal subjectivity, encouraging individuals to experience death as
      disease, to understand mortality as morbidity, and to approach living
      instrumentally as a means to longevity. This article uses the example of
      hypertension management to illustrate how this vision of death is transformed
      into a form of life. Through the analysis of a number of disciplinary
      technologies--from technical definitions of health to blood pressure monitoring-
      it illustrates how individuals are incited to relate to death in an antagonistic,
      impersonal, and technical fashion. While contemporary forms of capital
      accumulation in the health field require an intensification of such relations,
      this article suggests that there much to be gained from exploring visions of
      health that are not at odds with death.

PMID- 18073246
TI  - Constructing health news: possibilities for a civic-oriented journalism.
AB  - Health is a very prominent news category. However, we know little about the
      production processes of journalists leading to the health stories we encounter on
      a daily basis. Such knowledge is crucial for ensuring a vibrant public sphere for
      health. This article draws on interviews with eight health journalists in New
      Zealand to document what they consider to constitute a health story, their
      professional norms and practices, their perceptions of audiences, and the need
      for increased civic deliberations regarding health. Journalists privilege
      biomedical stories involving lifestyle and individual responsibility, and have
      limited frames for presenting stories that involve socio-political concerns.
      Stories are strongly shaped by journalists' considerations of their target
      audience, the sources they draw on, their professional norms, and institutional
      practices. This results in the omission of stories that have relevance for
      minority and disadvantaged groups and limits the nature of the stories told to
      ones that reflect the views of the majority. However, journalists are also
      reflective about these issues and receptive to ways to overcome them. This raises
      possibilities for health researchers to engage with journalists in order to
      repoliticise health and promote a more civic-oriented form of health journalism.

PMID- 18073247
TI  - 'I'd rather not take Prozac': stigma and commodification in antidepressant
      consumer narratives.
AB  - This article explores the idea that narrative is the primary vehicle through
      which antidepressant consumers negotiate their sense of identity and reality.
      Antidepressant consumers represent a unique consumer culture because of the
      stigma that society attaches to mental illness. Recent media attention, including
      direct to consumer (DTC) advertising, appears to decrease the stigma surrounding
      antidepressant use while at the same time commodifying and branding them for mass
      consumption. Antidepressant consumers must negotiate the threat of stigma and the
      threat of commodification through the process of constructing narratives.
      Exploring the narrative process of identity negotiation reveals how the
      interconnected cultural processes of stigma and commodification are undergoing
      historical shifts. Among these shifts are the intensification of branding and an
      expansion of consumer culture. Implications for health promotion and further
      research are discussed.

PMID- 18073249
TI  - News media coverage of direct-to-consumer pharmaceutical advertising:
      implications for countervailing powers theory.
AB  - Since a 1997 regulatory shift on the part of the US Food and Drug Administration
      (FDA), there has been an explosion of televised direct-to-consumer (DTC)
      pharmaceutical advertising in the United States. The introduction and growth of
      this form of advertising, as well as other recent evolutions in the health care
      arena, have altered relationships among key countervailing powers in the health
      care system, suggesting the need to recast countervailing powers theory so as to
      account for these changes. Coming from the perspective that the news media play
      an important role in reflecting the balance of power among the various
      countervailing powers, the paper advances this theoretical framework through an
      empirical assessment of the relative prominence of those entities in print news
      media coverage of the DTC advertising phenomenon. The study finds that ;corporate
      sellers' (pharmaceutical industry) are accorded more prominence in news coverage
      than are providers, consumers, corporate purchasers, or state players and that
      DTC critics, in particular, have minimal representation. In addition, the
      findings point toward two modifications for countervailing powers theory: (1) an
      incorporation of the role of academic/research organizations, and (2) a
      consideration of the universe of possibilities with respect to each of the
      countervailing powers.

PMID- 18073248
TI  - Redefining accountability in health care: managing the plurality of medical
      interests.
AB  - Conflict in health service delivery is common. It is often attributed to disputes
      between clinicians and patients or their families about treatment decisions and
      is particularly common in intensive care units (ICUs), in the form of ;futility
      disputes' between families and medical clinicians about decisions to terminate
      the active treatment of a dying family member. More common, but less prominent in
      the literature, is conflict within the medical profession about patient care
      goals and treatment. We contend that managing the plurality of medical interests
      is essential in achieving a more managed and positive experience for patients and
      families of the care they receive, and for achieving standards of quality and
      resource use. From an ethnographic study undertaken in a large ICU in Sydney,
      Australia, we found that the knowledge and practice differences of multiple
      medical decision-makers generated conflict, inconsistency of practice and
      subjectivity of decision-making that impeded coherent clinical decision-making
      and integrated patient care planning, coordination and care review. Improving
      patients' and families' experience of care requires medical clinicians and
      medical managers to accept responsibility for institutionalizing effective
      communication and decision-making processes within clinical networks and between
      clinical and managerial domains. Thus, strategies to improve patient care will
      need to extend beyond the medical profession to incorporate administrative
      management. We conclude that restructuring communication and decision-making
      processes is imperative to achieve clinical accountability in the workplace and
      systems accountability in the organization.

PMID- 18073250
TI  - Sustained response to anakinra in ankylosing spondylitis.

PMID- 18073251
TI  - Supportive and palliative care research collaboratives in the United Kingdom: an
      unnatural experiment?

PMID- 18073252
TI  - Flecainide for the treatment of chronic neuropathic pain: a Phase II trial.
AB  - BACKGROUND: Management of neuropathic pain is challenging. Medications that
      interfere with sodium channel transport, such as lidocaine, mexilitene and
      flecainide, are promising as analgesics. OBJECTIVE: In a general population of
      patients with a working diagnosis of neuropathic pain, whether if flecainide
      produces enough of an improvement in pain to warrant further clinical study is
      determined. DESIGN: Phase I/II prospective exploratory clinical trial. Eligible
      patients were observed for week 1, then 50 mg flecainide was administered twice
      daily for week 2 and then administered 100 mg twice daily for week 3. SETTING/
      SUBJECTS: Multi-institutional members of the Eastern Co-operative Oncology Group.
      Patients had neuropathic pain diagnosed by their oncologists as defined by the
      International Association for the Study of Pain and a diagnosis of cancer or
      AIDS. MEASUREMENTS: The Wisconsin Brief Pain Inventory was used. The primary
      endpoint was a decrease of 3 points (0-10 numerical scale) or a decrease of 50%
      in the worst pain rating at either day 15 or day 22 relative to the average of
      days 1 and 8 ratings. RESULTS: Nineteen patients were registered for the study.
      Four patients were ineligible. Of the remaining 15, one was unevaluable due to
      incomplete pain rating. Four out of 14 patients had an average drop of 5 points
      or 53% in their worst pain ratings on a 0-10 numerical scale of pain. No patients
      withdrew from study because of toxicity. There were no life-threatening or lethal
      toxicities. All patients were alive at the time of the analysis. CONCLUSIONS:
      Flecainide produced a 30% response rate. Response in this study was defined to be
      highly relevant and clinically significant reduction in pain. The drug merits
      study in a randomized placebo-controlled trial.

PMID- 18073253
TI  - Assessing physical functioning: a systematic review of quality of life measures
      developed for use in palliative care.
AB  - BACKGROUND: Physical decline is experienced by all palliative care patients and
      affects most aspects of life. Physical functioning (PF) is therefore a crucial
      domain for quality of life (Qol) assessments. The purpose of this study was to
      review how PF assessments are performed in Qol instruments developed for
      palliative care METHODS: For identification of instruments, Medline searches up
      to April 2005 were performed using the terms (palliative care OR end of life care
      OR terminal care) AND quality of life AND (assessment OR instrument OR
      questionnaire). A total of 1326 hits were screened. Named QoL instruments were
      extracted from 240 abstracts and 46 relevant reports. Items assessing PF were
      then identified and classified according to activity domains as described by the
      WHO International Classification of Functioning Disability and Health. RESULTS:
      Of 224 different instruments detected, 39 were identified as developed for
      palliative care. Of these, 11 included original PF assessments. Two were
      comprehensive performance status measures made for staff assessment, 9 were
      multidimensional tools including 2-7 PF items. The content and phrasing of items
      varied considerably. All instruments included some aspects of self-care, whereas
      the coverage of mobility, domestic, work--and leisure activities was
      inconsistent. INTERPRETATION: Despite its importance, PF assessment seems to be a
      minor part of palliative care QoL instruments. Clear definitions and
      conceptualization of PF are needed, as well as a consensus on relevant aspects to
      include in improved instruments. Performance scales already developed should be
      further explored with regard to content, validity and psychometric properties.

PMID- 18073254
TI  - Official certification of doctors working in palliative medicine in Europe: data
      from an EAPC study in 52 European countries.
AB  - There is an increasing move to recognize palliative medicine as an area of
      certificated specialization. Drawing on a survey of palliative care provision in
      the World Health Organization European region, an overview of palliative care
      specialization and accreditation practices was presented. Within an international
      survey to key experts in palliative care carried out in 2005, conducted in 52
      countries, a question about the certification for palliative care professionals
      was included. Information was obtained for 43 of the 52 countries surveyed and
      all 43 countries (83%) provided data on certification. Palliative medicine has
      specialty status in just two European countries: Ireland and the UK. In five
      countries it is considered as a sub-specialty, for which a second certification
      is required: Poland, Romania, Slovakia and Germany and, recently, France. Some 10
      other countries have started the process of certification for palliative
      medicine, in all cases opting for sub-specialty status that follows full
      recognition in an established specialty. Across countries there is disparity in
      the certification criteria followed and considerable variability in the demands
      that are made in order to achieve certification. Further studies are needed to
      focus in depth on palliative medicine certification and accreditation across
      Europe. Establishing uniform approaches to certification for palliative medicine
      in different European countries will contribute to wider take-up of specialty
      status and the improved recognition of palliative care as a discipline.

PMID- 18073255
TI  - Supportive and palliative care needs of families of children with life
      threatening illnesses in Western Australia: evidence to guide the development of
      a palliative care service.
AB  - OBJECTIVE: To obtain feedback from families of children receiving palliative and
      supportive care about their care needs in hospital and in community settings.
      DESIGN: A two-phase combined quantitative and qualitative study. SETTING: Western
      Australia. PARTICIPANTS: 134 parents and 20 service providers. RESULTS: Analysis
      indicated the concept of palliative care is poorly understood by health
      professionals and by parents. Many families are affected emotionally, financially
      and physically by the burden of caring for children with life threatening or
      chronic conditions requiring complex care at home. Parents indicated the need for
      clear and honest information about their child's condition and prognosis
      throughout the trajectory of illness and perceived this had been lacking.
      Families required financial and practical assistance with providing care from
      their children at home. Parents also wanted more practical resources and
      information to assist with the management of their child's nutrition and pain, as
      well as support for their other children. The level of respite (in home and
      residential) was perceived to be insufficient and inequitable. Parents also
      required access to, and advice from, multidisciplinary health professionals when
      caring for their child at home. There was a perceived lack of coordination
      between community services and the hospital. CONCLUSION: Education of health
      professionals and parents regarding the concepts and introduction of palliative
      and supportive care is required. Care for children and their families should be
      coordinated by a multidisciplinary team in consultation with children and their
      families, and linked and integrated with the treating hospital in collaboration
      with community services. More inclusive criteria are required for community
      services including practical aids and respite care.

PMID- 18073256
TI  - Obstacles to the delivery of primary palliative care as perceived by GPs.
AB  - INTRODUCTION: In order to facilitate GPs in their work and increase the
      possibilities for patients to remain at home, it is important to identify the
      obstacles which hinder the delivery of primary palliative care. From previous
      research we learned about some of the problems experienced by GPs. In this survey
      we aimed to identify the prevalence of such problems in providing palliative care
      and its determinants. METHODS: The prevalence of obstacles and its determinants
      were identified by a questionnaire to 320 GPs in three regions of the
      Netherlands. Obstacles were grouped as follows: communication, organisation & co
      ordination of care, knowledge & expertise, integrated care, time for relatives.
      The potential determinants were GP characteristics and expertise development
      activities. RESULTS: The response rate was 62.3%. GPs experienced considerable
      obstacles in all aspects of palliative care. The most prevalent were: problems
      with bureaucratic procedures (83.9%), the time necessary to arrange home care
      technology (61.1%) and the difficulties accompanied with the wish or necessity to
      obtain extra care (56.3%). In general, more years of GP experience and the
      participation in (multidisciplinary) case discussions were associated with less
      perceived obstacles. DISCUSSION: Based on the results of our survey policymakers
      and practitioners can plan and set priorities in handling the obstacles. There is
      a high necessity of firstly overcoming the barriers within organisation and
      coordination of care. Furthermore, our study can help in choosing the
      (additional) expertise needed in the future and in the realisation of the
      preferred expertise advancement activities.

PMID- 18073257
TI  - Urbanization and place of death for the elderly: a 10-year population-based
      study.
AB  - OBJECTIVES: To explore the association between the place of death and the level
      of urbanization within the communities where the elderly were residing at the
      time of their death. METHODS: A retrospective, population-based, cross-sectional
      study set in Taiwan, involving a total of 697,814 eligible deaths occurred
      between 1995 and 2004, among elderly people (aged 65 years or above). RESULTS:
      After adjusting for other factors, the multilevel logistic regression analyses
      showed that home death was associated with lower levels of urbanization; as
      compared with participants living in the highest urbanization level (level 1),
      the respective adjusted odds of dying at home were 1.600, 2.769, 3.774, 4.481,
      4.003 and 4.717 times for those living in the areas from the second highest to
      the lowest urbanization levels (levels 2-7). CONCLUSIONS: After adjusting for
      other socio-demographic, clinical and healthcare factors, the place of death has
      a significant association with the level of urbanization among the elderly.

PMID- 18073258
TI  - Akathisia and an unusual symptomatic treatment: a case report.
AB  - We present a case of medication-induced akathisia in a 47-year-old woman with
      metastatic carcinoma of the ovary. Severe pacing and restlessness started after
      commencing a subcutaneous infusion with cyclizine 150 mg, haloperidol 2.5 mg and
      oxycodone 20 mg. She was also taking levomepromazine and fluoxetine orally at the
      time. By making changes to her medication, her symptoms resolved gradually.
      During the time of convalescence, she gained great symptomatic relief from using
      exercise pedals and it allowed her to go about usual everyday activities, such as
      eating and reading, while continuously treading the pedals.

PMID- 18073259
TI  - Akathisia and an unusual symptomatic treatment.

PMID- 18073260
TI  - Does pamidronate enhance the analgesic effect of radiotherapy? A randomized
      trial.

PMID- 18073261
TI  - Knowledge of attitudes to opioids in palliative care patients.

PMID- 18073262
TI  - Use of nebulised adrenaline in the management of steroid-resistant stridor.

PMID- 18073263
TI  - Intractable nausea and vomiting successfully related with granisetron 5
      hydroxytryptamine type 3 receptor antagonists in Palliative Medicine.

PMID- 18073264
TI  - A functional polymorphism of TIR-domain-containing adaptor protein is not
      associated with axial spondyloarthritis.
AB  - OBJECTIVE: A genetic variant of the toll-like receptor (TLR)2/4 adaptor protein
      TIRAP (single nucleotide polymorphism (SNP) C539T) was identified in a UK and in
      several African populations. The heterozygous genotype of this SNP has been
      associated with protection from severe infections. This allele results in an
      attenuated response to bacterial pathogens. As an exaggerated innate immune
      response to pathogens has been implicated in spondyloarthritis (SpA)
      pathogenesis, we analysed if the heterozygous C/T genotype was underrepresented
      in axial SpA compared with healthy controls. METHODS: 204 patients with axial SpA
      and 175 population-matched controls were included. SNP C539T was determined with
      a sequence-specific polymerase chain reaction and direct sequencing. RESULTS: The
      frequency of the haplotypes was similar in cases and controls (87% for C and 13%
      for T in both groups). The C/T genotype, which attenuates TLR signalling, was not
      underrepresented in cases versus controls (19% in controls vs 24% in cases, p =
      0.44). The T/T genotype, was slightly lower in cases than in controls, although
      this was not significant (3.4% in controls vs 1% in cases, p = 0.15). Within the
      cases, there were no differences in disease phenotype or activity between
      patients with the C/C or C/T genotype. CONCLUSIONS: This study did not show
      significant associations of SNP S180L of the TLR2/4 adaptor protein TIRAP with
      axial SpA.

PMID- 18073265
TI  - Gaze control and foot kinematics during stair climbing: characteristics leading
      to fall risk in progressive supranuclear palsy.
AB  - BACKGROUND AND PURPOSE: Does gaze control influence lower-extremity motor
      coordination in people with neurological deficits? The purpose of this study was
      to determine whether foot kinematics during stair climbing are influenced by gaze
      shifts prior to stair step initiation. SUBJECTS AND METHODS: Twelve subjects with
      gaze palsy (mild versus severe) secondary to progressive supranuclear palsy were
      evaluated during a stair-climbing task in a cross-sectional study of mechanisms
      influencing eye-foot coordination. Infrared oculography and electromagnetic
      tracking sensors measured eye and foot kinematics, respectively. The primary
      outcome measures were vertical gaze fixation scores, foot lift asymmetries, and
      sagittal-plane foot trajectories. RESULTS: The subjects with severe gaze palsy
      had significantly lower lag foot lift relative to lead foot lift than those with
      a mild form of gaze palsy. The lag foot trajectory for the subjects with severe
      gaze palsy tended to be low, with a heading toward contact with the edge of the
      stair. SUBJECTS: with severe gaze palsy were 28 times more likely to experience
      "fixation intrusion" (high vertical gaze fixation score) during an attempted
      shift of gaze downward than those with mild ocular motor deficits (odds ratio
      [OR]=28.3, 95% confidence interval [CI]=6.4-124.8). Subjects with severe gaze
      shift deficits also were 4 times more likely to have lower lag foot lift with
      respect to lead foot lift than those with mild ocular motor dysfunction (OR=4.0,
      95% CI=1.7-9.7). DISCUSSION AND CONCLUSION: The small number of subjects and the
      variation in symptom profiles make the generalization of findings preliminary.
      Deficits in gaze control may influence stepping behaviors and increase the risk
      of trips or falls during stair climbing. Neural and kinematic hypotheses are
      discussed as possible contributing mechanisms.

PMID- 18073266
TI  - Interrater reliability of the Movement Assessment Battery for Children.
AB  - BACKGROUND AND PURPOSE: The Movement Assessment Battery for Children (M-ABC) is a
      widely used, standardized assessment of motor performance in children. The total
      score obtained on this test often is used to identify children who are either
      definitely impaired or at risk for motor impairment. The purpose of this study
      was to determine the interrater reliability of data for the M-ABC when scored by
      pediatric physical therapists working in routine clinical settings. SUBJECTS AND
      METHODS: For 9 children who were referred to clinical settings for an assessment
      of possible movement difficulties, performance on the appropriate age band of the
      M-ABC was videotaped. The 9 children, one at each age from 4 through 12 years,
      represented all ages covered by the test. The videotaped performances were rated
      according to the test instructions by 131 pediatric physical therapists with a
      range of experience and by an expert rater who developed the Dutch version of the
      test. RESULTS: The average agreement between therapists in their classification
      of the children was very high. The kappa coefficients for the 9 videos ranged
      from .95 to 1.00. DISCUSSION AND CONCLUSION: Errors made by the therapists could
      be classified as those that might be common to all tests and those that are
      specific to the M-ABC.

PMID- 18073267
TI  - Scales to assess the quality of randomized controlled trials: a systematic
      review.
AB  - BACKGROUND AND PURPOSE: The methodological quality of randomized controlled
      trials (RCTs) is commonly evaluated in order to assess the risk of biased
      estimates of treatment effects. The purpose of this systematic review was to
      identify scales used to evaluate the methodological quality of RCTs in health
      care research and summarize the content, construction, development, and
      psychometric properties of these scales. METHODS: Extensive electronic database
      searches, along with a manual search, were performed. RESULTS: One hundred five
      relevant studies were identified. They accounted for 21 scales and their
      modifications. The majority of scales had not been rigorously developed or tested
      for validity and reliability. The Jadad Scale presented the best validity and
      reliability evidence; however, its validity for physical therapy trials has not
      been supported. DISCUSSION AND CONCLUSION: Many scales are used to evaluate the
      methodological quality of RCTs, but most of these scales have not been adequately
      developed and have not been adequately tested for validity and reliability. A
      valid and reliable scale for the assessment of the methodological quality of
      physical therapy trials needs to be developed.

PMID- 18073268
TI  - Awareness during anesthesia.

PMID- 18073269
TI  - Development of medical checklists for improved quality of patient care.
AB  - BACKGROUND: Checklists are used in both medical and non-medical industries as
      cognitive aids to guide users through accurate task completion. Their development
      requires a systematic and comprehensive approach, particularly when implemented
      in high intensity fields such as medicine. OBJECTIVE: A narrative review of the
      literature was conducted to outline the methodology to designing and implementing
      clear and effective medical checklists. METHODS: We systematically searched for
      relevant English-language medical and non-medical literature both to describe
      where checklists have been demonstrated to improve delivery of care and also, how
      to develop valid checklists. RESULTS: The MEDLINE search yielded 8303 citations
      of which 1042 abstracts were reviewed. On the basis of criteria for inclusion and
      subsequent full-manuscript review, 178 sources, including 17 non-medical
      publications, were included in the narrative review. This information was further
      supplemented by expert opinion in the area of checklist development and
      implementation. A small number of strategies for designing effective checklists
      were referenced in the literature, including utilization of pre-published
      guidelines, formation of expert panels and repeat pilot-testing of preliminary
      checklists. CONCLUSION: Despite currently available evidence, a highly effective,
      standardized methodology for the development and design of medical-specific
      checklists has not previously been developed and validated, which has likely
      contributed to their inconsistent use in several key fields of medicine, despite
      evidence of their fundamental role in error management.

PMID- 18073270
TI  - Comparing patient reports about hospital care across a Canadian-US border.
AB  - OBJECTIVE: To compare patient reports about hospital care between western New
      York State and southern Ontario using a random intercept model. METHOD: Cross
      sectional survey of 3923 patients who received medical or surgical care between
      August and October 2004 at 28 hospitals (14 hospitals per jurisdiction). Thirty
      five questions were combined to calculate eight indicators with scores ranging
      from 0 to 100 (best care experience). For each indicator, a model was built where
      the region (western New York vs. southern Ontario) was included as a fixed effect
      with hospital as random within region. A number of patient characteristics were
      also included as fixed effects. RESULTS: The effect of the region was
      statistically significant (P < 0.05) only for the models predicting the
      'continuity and transition', 'involvement of family' and 'physical comfort'
      indicator scores. The differences were 10.66, 4.05 and -3.23 points,
      respectively. In all three models, the random intercepts were not statistically
      significant, indicating that the differences above did not vary by hospitals. The
      model predicting 'overall impression' scores, however, showed a random intercept
      statistically significant (P = 0.026). The individual-level explained proportion
      of variance ranged from 5.68 to 11.22%, and the hospital-within-region-level
      explained proportion of variance ranged from 2.19 to 52.28%. CONCLUSION: The
      difference observed on the 'continuity and transition' indicator might be the
      only one somewhat meaningful, and might be explained by health maintenance
      organization reimbursements' mechanisms and hospital quality improvement
      initiatives available in western New York, as well as by the fact that occupancy
      rates in western New York border the 60% compared with the 95% in southern
      Ontario.

PMID- 18073271
TI  - Aging alters gene expression of growth and remodeling factors in human skeletal
      muscle both at rest and in response to acute resistance exercise.
AB  - The purpose of this investigation was to compare expression of genes that
      function in inflammation and stress, cell structure and signaling, or remodeling
      and growth in skeletal muscle of young (32 +/- 7 yr, n = 15) and elderly (72 +/-
      5 yr, n = 16) healthy subjects before and after a bout of resistance leg
      exercises. A real-time RT-PCR method was used to screen 100 transcripts in v.
      lateralis biopsies obtained before and 72 h postexercise. The screen identified
      15 candidates for differential expression due to aging and/or exercise that were
      measured quantitatively. The median levels of four mRNAs (insulin-like growth
      factor-1 and its binding protein IGFBP5, ciliary neurotrophic factor, and the
      metallopeptidase MMP2) were significantly affected by aging and were greater (1.6
      to 2.3-fold, P </= 0.05) in the young than elderly muscle at both time points.
      The median levels of three mRNAs were significantly (P </= 0.05) affected by
      exercise in the young. The metallopeptidase inhibitor TIMP1 and alpha-cardiac
      actin mRNAs increased 2-fold and 6.5-fold, respectively, and GDF8 (myostatin)
      mRNA decreased by 50%. However, elderly muscle did not display any significant
      changes in gene expression postexercise. Thus, aging muscle shows decreased
      levels at rest and an impaired response to exercise for a number of mRNAs for
      factors potentially involved in muscle growth and remodeling. Future studies must
      determine the functional importance of these gene expression changes to protein
      synthesis, satellite cell activity, and other processes that are directly
      involved in the mechanisms of muscle hypertrophy.

PMID- 18073272
TI  - Effects of short-term growth hormone treatment on liver and muscle transcriptomes
      in rainbow trout (Oncorhynchus mykiss).
AB  - Although studies have established that exogenous growth hormone (GH) treatment
      stimulates growth in fish, its effects on target tissue gene expression are not
      well characterized. We assessed the effects of Posilac (Monsanto, St. Louis, MO),
      a recombinant bovine GH, on tissue transcript levels in rainbow trout selected
      from two high-growth rate and two low-growth rate families. Transcript abundance
      was measured in liver and muscle with the Genome Research in Atlantic Salmon
      Project (GRASP) 16K cDNA microarray. A selection of the genes identified as
      altered by the microarray and transcripts for insulin-like growth factors, growth
      hormone receptors (GHRs), and myostatins were measured by real-time PCR in the
      liver, muscle, brain, kidney, intestine, stomach, gill, and heart. In general,
      transcripts identified as differentially regulated in the muscle on the
      microarray showed similar directional changes of expression in the other
      nonhepatic tissues. A total of 114 and 66 transcripts were identified by
      microarray as differentially expressed with GH treatment across growth rate for
      muscle and liver, respectively. The largest proportion of these transcripts
      represented novel transcripts, followed by immune and metabolism-related genes.
      We have identified a number of genes related to lipid metabolism, supporting a
      modulation in lipid metabolism following GH treatment. Most notable among the
      growth-axis genes measured by real-time PCR were increases in GHR1 and -2
      transcripts in liver and muscle. Our results indicate that short-term GH
      treatment activates the immune system, shifts the metabolic sectors, and
      modulates growth-regulating genes.

PMID- 18073273
TI  - Suppression of 11beta-hydroxysteroid dehydrogenase type 1 with RNA interference
      substantially attenuates 3T3-L1 adipogenesis.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which regulates the
      local level of glucocorticoids, has been suggested to be involved in the
      development of obesity. A definitive functional role for 11beta-HSD1 in
      adipogenesis, however, remains to be established. We developed 3T3-L1 cell lines
      stably transfected with a small hairpin RNA (shRNA) targeting 11beta-HSD1. A
      shRNA containing two nucleotide substitutions was used as a control. Silencing of
      11beta-HSD1 substantially attenuated the accumulation of lipid droplets and the
      expression of adipogenesis marker genes, which was induced by a mixture
      containing either corticosterone or dexamethasone. Silencing of 11beta-HSD1
      increased the concentration of 11-dehydrocorticosterone in the culture
      supernatant but did not significantly affect the levels of corticosterone or
      dexamethasone. Translocation of glucocorticoid receptors to the nucleus in
      response to glucocorticoids was significantly attenuated by silencing 11beta
      HSD1. The number of cells entering the S phase of the cell cycle following the
      induction of adipogenesis was significantly reduced by silencing 11beta-HSD1.
      11beta-HSD1 shRNA delivered by lentiviral vectors after the induction of
      differentiation, however, did not affect the progression of adipogenesis. These
      results indicate that 11beta-HSD1 plays a significant functional role in the
      initiation of 3T3-L1 adipogenesis and provide new mechanistic insights into the
      role of 11beta-HSD1 in the development of obesity and related diseases.

PMID- 18073274
TI  - Cell-based and biochemical structure-activity analyses of analogs of the
      microtubule stabilizer dictyostatin.
AB  - Compounds that bind to microtubules (MTs) and alter their dynamics are highly
      sought as a result of the clinical success of paclitaxel and docetaxel. The
      naturally occurring compound (-)-dictyostatin binds to MTs, causes cell cycle
      arrest in G(2)/M at nanomolar concentrations, and retains antiproliferative
      activity in paclitaxel-resistant cell lines, making dictyostatin an attractive
      candidate for development as an antineoplastic agent. In this study, we examined
      a series of dictyostatin analogs to probe biological and biochemical structure
      activity relationships. We used a high-content multiparameter fluorescence-based
      cellular assay for MT morphology, chromatin condensation, mitotic arrest, and
      cellular toxicity to identify regions of dictyostatin that were essential for
      biological activity. Four analogs (6-epi-dictyostatin, 7-epi-dictyostatin, 16
      normethyldictyostatin, and 15Z,16-normethyldictyostatin) retained low nanomolar
      activity in the cell-based assay and were chosen for analyses with isolated
      tubulin. All four compounds were potent inducers of MT assembly. Equilibrium
      binding constant (K(i)) determinations using [(14)C]epothilone B, which has a 3
      fold higher affinity for the taxoid binding site than paclitaxel, indicated that
      6-epi-dictyostatin and 7-epi-dictyostatin displaced [(14)C]epothilone B with K(i)
      values of 480 and 930 nM, respectively. 16-Normethyldictyostatin and 15Z,16
      normethyldictyostatin had reduced affinity (K(i) values of 4.55 and 4.47 muM,
      respectively), consistent with previous reports showing that C16
      normethyldictyostatin loses potency in paclitaxel-resistant cell lines that have
      a Phe270-to-Val mutation in the taxoid binding site of beta-tubulin. Finally, we
      developed a set of quantitative structure-activity relationship equations
      correlating structures with antiproliferative activity. The equations accurately
      predicted biological activity and will help in the design of future analogs.

PMID- 18073275
TI  - Targeted deletion of cannabinoid receptors CB1 and CB2 produced enhanced
      inflammatory responses to influenza A/PR/8/34 in the absence and presence of
      Delta9-tetrahydrocannabinol.
AB  - We have previously reported that Delta-9-tetrahydrocannabinol (Delta(9)-THC)
      treated mice challenged with influenza virus A/PR/8/34 (PR8) developed increased
      viral hemagglutinin 1 (H1) mRNA levels and decreased monocyte and lymphocyte
      recruitment to the pulmonary airways when compared with mice challenged with PR8
      alone. The objective of the present study was to examine the role of cannabinoid
      (CB(1)/CB(2)) receptors in mediating the effects of Delta(9)-THC on immune and
      epithelial cell responses to PR8. In the current study, Delta(9)-THC-treated
      CB(1)/CB(2) receptor null (CB(1)-/-/CB(2)-/-) and wild-type mice infected with
      PR8 had marked increases in viral H1 mRNA when compared with CB(1)-/-/CB(2)-/-
      and wild-type mice challenged with PR8 alone. However, the magnitude of the H1
      mRNA levels was greatly reduced in CB(1)-/-/CB(2)-/- mice as compared with wild
      type mice. In addition, Delta(9)-THC-treated CB(1)-/-/CB(2)-/- mice infected with
      PR8 had increased CD4+ T cells and IFN-gamma in bronchoalveolar lavage fluid with
      greater pulmonary inflammation when compared with Delta(9)-THC-treated wild-type
      mice infected with PR8. Delta(9)-THC treatment of CB(1)-/-/CB(2)-/- mice in the
      presence or absence of PR8 challenge also developed greater amounts of mucous
      cell metaplasia in the affected bronchiolar epithelium. Collectively, the immune
      and airway epithelial cell responses to PR8 challenge in Delta(9)-THC-treated
      CB(1)-/-/CB(2)-/- and wild-type mice indicated the involvement of CB(1)/CB(2)
      receptor-dependent and -independent mechanisms.

PMID- 18073276
TI  - Allocating forage to fall-calving cow-calf pairs strip-grazing stockpiled tall
      fescue.
AB  - In a 2-yr study, we evaluated the effect of different forage allocations on the
      performance of lactating beef cows and their calves grazing stockpiled tall
      fescue. Allocations of stockpiled tall fescue at 2.25, 3.00, 3.75, and 4.50% of
      cow-calf pair BW/d were set as experimental treatments. Conventional hay-feeding
      was also evaluated as a comparison to grazing stockpiled tall fescue. The
      experiment had a randomized complete block design with 3 replications and was
      divided into 3 phases each year. From early December to late February (phase 1)
      of each year, cows and calves grazed stockpiled tall fescue or were fed hay in
      the treatments described above. Immediately after phase 1, cows and calves were
      commingled and managed as a single group until weaning in April (phase 2) so that
      residual effects could be documented. Residual effects on cows were measured
      after the calves were weaned in April until mid-July (phase 3). During phase 1 of
      both years, apparent DMI of cow-calf pairs allocated stockpiled tall fescue at
      4.50% of BW/d was 31% greater (P < 0.01) than those allocated 2.25% of BW/d. As
      allocation of stockpiled tall fescue increased from 2.25 to 4.50% of cow-calf
      BW/d, pasture utilization fell (P < 0.01) from 84 +/- 7% to 59 +/- 7%. During
      phase 1 of both years, cow BW losses increased linearly (P < 0.02) as forage
      allocations decreased, although the losses in yr 1 were almost double (P < 0.01)
      those in yr 2. During phases 2 and 3, few differences were noted across treatment
      groups, such that by the end of phase 3, cow BW in all treatments did not differ
      either year (P > 0.40). Calf ADG in phase 1 increased linearly (P < 0.01) with
      forage allocation (y = 0.063x + 0.513; R(2) = 0.91). However, calf gain per
      hectare decreased linearly (P < 0.01) as stockpiled tall fescue allocations
      increased (y = -26.5x + 212; R(2) = 0.97) such that gain per hectare for cow-calf
      pairs allocated stockpiled tall fescue at 4.50% BW/d was nearly 40% less (P <
      0.01) than for those allocated 2.25% of BW/d. Allocating cow-calf pairs
      stockpiled tall fescue at 2.25% of BW/d likely optimizes its use; because cow
      body condition is easily regained in the subsequent spring and summer months,
      less forage is used during winter, and calf gain per hectare is maximized.

PMID- 18073277
TI  - Use of phytogenic products as feed additives for swine and poultry.
AB  - This article summarizes the experimental knowledge on efficacy, possible modes of
      action, and aspects of application of phytogenic products as feed additives for
      swine and poultry. Phytogenic feed additives comprise a wide variety of herbs,
      spices, and products derived thereof, and are mainly essential oils. The
      assumption that phytogenic compounds might improve the palatability of feed has
      not yet been confirmed by choice-feeding studies. Although numerous studies have
      demonstrated antioxidative and antimicrobial efficacy in vitro, respective
      experimental in vivo evidence is still quite limited. The same applies to the
      supposition that phytogenic compounds may specifically enhance activities of
      digestive enzymes and nutrient absorption. Nevertheless, a limited number of
      experimental comparisons of phytogenic feed additives with antibiotics and
      organic acids have suggested similar effects on the gut, such as reduced
      bacterial colony counts, fewer fermentation products (including ammonia and
      biogenic amines), less activity of the gut-associated lymphatic system, and a
      greater prececal nutrient digestion, probably reflecting an overall improved gut
      equilibrium. In addition, some phytogenic compounds seem to promote intestinal
      mucus production. Such effects may explain a considerable number of practical
      studies with swine and poultry reporting improved production performance after
      providing phytogenic feed additives. In total, available evidence indicates that
      phytogenic feed additives may add to the set of nonantibiotic growth promoters
      for use in livestock, such as organic acids and probiotics. However, a systematic
      approach toward the efficacy and safety of phytogenic compounds used as feed
      additives for swine and poultry is still missing.

PMID- 18073278
TI  - Influence of dry-rolling and tempering agent addition during the steam-flaking of
      sorghum grain on its feeding value for feedlot cattle.
AB  - Two experiments were conducted to evaluate the influence of dry-rolling (DRS) and
      tempering agent (TA) addition during the steam-flaking of grain sorghum (SFS) for
      feedlot cattle. Five dietary treatments were compared: 1) DRS; 2) SFS, no TA; 3)
      SFS, 0.275 mg/kg of TA; 4) SFS, 1.375 mg/kg of TA; and 5) SFS, 2.750 mg/kg of TA.
      Bulk densities of DRS and SFS were 0.48 and 0.36 kg/L, respectively. Diets
      contained 70.6% grain sorghum (DM basis). One hundred fifty crossbred steers (336
      kg of BW) were used in a 115-d finishing experiment to evaluate treatment effects
      on feedlot performance. Body weight gain averaged 1.49 kg/d and was not affected
      (P = 0.47) by treatments. The SFS reduced (P < 0.01) DMI (9%) and enhanced (P <
      0.01) G:F (13%) and the NE(m) and NE(g) value of the diet (9 and 11%,
      respectively). Use of a TA before flaking sorghum did not influence (P > 0.20)
      cattle growth performance or NE(m) or NE(g) value of the diet. Given that the
      NE(m) and NE(g) values of DRS are 2.00 and 1.35 Mcal/kg, respectively (NRC,
      1996), the corresponding values for SFS were 2.28 and 1.59 Mcal/kg. Five steers
      (397 kg of BW) with ruminal and duodenal cannulas were used in a 5 x 5 Latin
      square design to evaluate treatment effects on digestive function. Ruminal
      digestion of OM and starch was greater (14 and 16%, respectively; P < 0.01) for
      SFS vs. DRS. Steam-flaking sorghum increased (P < 0.01) postruminal digestion of
      OM (11%), N (10%), and starch (25%) and total tract digestion (P < 0.01) of OM
      (8.3%), N (8.2%), and starch (8.9%). Grain processing did not affect (P > 0.20)
      ruminal pH or VFA molar proportions. There was a cubic component (P < 0.10) to
      level of TA on ruminal pH and VFA molar proportions, with values being optimal at
      1.375 mg/kg of tempering agent. It is concluded that steam-flaking grain sorghum
      will increase its NE value for maintenance and gain (14 and 18%, respectively)
      and enhance the MP value of the diet due to greater intestinal N digestion. The
      use of a TA to enhance the mechanical efficiency of the flaking process may not
      otherwise benefit the feeding value of sorghum.

PMID- 18073279
TI  - Learned appetites for calcium, phosphorus, and sodium in sheep.
AB  - If supplemental minerals are needed to promote optimal animal performance, what
      is the best way of providing them: free choice or in the diet? We hypothesized
      that herbivores discriminate among feeds containing Na, P, and Ca and modify
      their choices as a function of need. One group of lambs was fed a basal diet low
      in P and high in Ca (low P-high Ca), whereas another group was fed a basal diet
      high in P and low in Ca (high P-low Ca). After 73 d of exposure to the unbalanced
      diets, the lambs were conditioned by offering flavored grape pomace containing
      NaCl, CaCO(3), or NaH(2)PO(4). Preference for pomace + minerals was determined
      when all lambs were fed a basal diet of alfalfa pellets and barley grain (initial
      preference) and during 4 phases. Phases 1 and 2 occurred after 40 and 67 d of
      feeding the unbalanced basal diets, phase 3 occurred after conditioning with
      NaCl, CaCO(3), or NaH(2)PO(4), and phase 4 occurred 22 d after the groups were
      moved to 2 new (separate) locations so the animals in the different groups could
      not eat dirt, urine, or feces from the other pen. Preference for pomace did not
      differ between the groups during the initial preference tests (P = 0.62); both
      groups preferred NaCl > CaCO(3) = NaH(2)PO(4) (P < 0.001). As the study
      progressed, and lambs fed low P-high Ca had lower P and greater Ca concentrations
      in serum than lambs fed high P-low Ca (P < 0.001), the preference between groups
      diverged. In phase 2, lambs in high P-low Ca continued to prefer NaCl (P <
      0.001), but lambs in low P-high Ca preferred NaH(2)PO(4) (P < 0.05). After
      conditioning, both groups preferred NaCl = NaH(2)PO(4) > CaCO(3) (P < 0.01 to
      0.11). After the groups were moved to different locations, lambs fed low P-high
      Ca showed the lowest concentration (3.7 mg/dL) of inorganic P in serum for all
      phases (P < 0.001), and they preferred NaH(2)PO(4) > NaCl = CaCO(3) (P < 0.001).
      In contrast, lambs in high P-low Ca avoided NaH(2)PO(4) (P < 0.05). Lambs offered
      high P-low Ca showed a greater preference for CaCO(3) (P = 0.12) and NaCl (P <
      0.05) and a lower preference for NaH(2)PO(4) compared with lambs fed low P-high
      Ca (P < 0.001). In summary, lambs discriminated among different flavored feeds
      containing NaCl, CaCO(3), and NaH(2)PO(4) and displayed preferences as a function
      of the mineral imbalance in their basal diets. Thus, it may be possible to feed
      Ca and P supplements free choice, such that individual animals within a group can
      manifest preferences based on their specific needs.

PMID- 18073280
TI  - Frequency of the HAL-1843 mutation of the ryanodine receptor gene in dead and
      nonambulatory-noninjured pigs on arrival at the packing plant.
AB  - Four Midwestern packing plants (designated as plants A, B, C, and D) were visited
      on 53 occasions, and tissue samples were collected postmortem from a total of
      2,019 pigs to determine the frequency of the HAL-1843 mutation of the ryanodine
      receptor gene in dead (DOA), nonambulatory-noninjured (NANI), and normal animals.
      The sampled pigs came from approximately 130,000 animals from 454 farms and were
      transported on 861 trailer loads, with an average of 152 pigs/load and an average
      pig live BW/load of 125 (SD 7.02) kg/pig. Frequency of animals with the HAL-1843
      mutation was low, with only 2.7% of the pigs being either homozygous recessives
      (nn, 0.45%) or carriers (Nn, 2.3%) for the mutation and 97.3% of the pigs being
      homozygous for the normal allele (NN). The mutation was present in all 3 classes
      of pig, with 1.8% of normal, 1.8% of NANI, and 4.7% of DOA animals having at
      least 1 copy. Two of the plants (A and C) had a greater frequency (P < 0.05) of
      carrier (3.7 and 3.5 vs. 1.1 and 1.0 for plants A and C vs. B and D,
      respectively) and homozygous recessive (1.0 and 0.9 vs. 0.0 and 0.0,
      respectively) animals than the others (plants B and D). There was a greater
      frequency (P < 0.05) of carriers in DOA animals than in the normal or NANI pigs
      (3.7 vs. 1.7 and 1.5 for DOA vs. normal and NANI, respectively). The 55 pigs that
      had at least 1 copy of the mutation came from 53 farms; therefore, the mutation
      was relatively widespread, being present in approximately 11% of the farms
      sampled. Although the HAL-1843 mutation is still present in commercial pig
      populations in the United States, its low frequency in DOA and NANI pigs suggests
      that it is not a major cause of these transport losses.

PMID- 18073281
TI  - Assessing genetic gain, inbreeding, and bias attributable to different flock
      genetic means in alternative sheep sire referencing schemes.
AB  - Flocks participating in sire referencing schemes can achieve greater genetic
      gains than those achievable by within-flock selection. However, requirements for
      joining these schemes can be prohibitive to some producers. The objectives of
      this study were to determine whether less restrictive schemes or schemes of
      shorter duration could achieve rates of gain and reduce inbreeding as efficiently
      as continuous sire referencing schemes (SRS) and to investigate whether bias from
      different genetic means could be reduced by these alternative schemes. Pedigree
      and performance data for a single trait with a within-flock heritability of 0.25
      were simulated (50 replications) for 15 flocks with 40 to 140 ewes per flock.
      Founder genetic means for each flock were sampled from a normal distribution with
      mean 0 and SD equal to the trait's genetic SD. After 10 yr of random mating,
      flocks had the opportunity to join an SRS and begin selection for the simulated
      trait. Yearling rams were chosen as reference sires randomly from the top one
      sixth of the population ranked on BLUP EBV. Every year, in each flock, 3
      reference sires were mated to 10 ewes. Six sire referencing scenarios were
      considered, in which all flocks participated in a SRS for 1) 15 yr; 2) 5 yr
      before discontinuing the scheme; 3) 10 yr before discontinuing the scheme; 4) 2
      out of every 3 yr; 5) 15 yr with reference sire mating by natural service; and 6)
      no years (no use of SRS). Ewes not mated to reference sires were mated either to
      their own home-bred sires exclusively or to a mixture of homebred and unrelated
      purchased rams of unknown merit. Genetic gain was equivalent whether the SRS used
      AI or natural service matings, although inbreeding was lower with natural
      service. Across all scenarios, genetic gain and inbreeding were greater when
      excess ewes were mated exclusively to homebred sires. Genetic gains without SRS
      were 80 to 82% lower than when the scheme operated for 15 yr, whereas inbreeding
      was considerably greater. Other scenarios were intermediate in both gain and
      inbreeding levels. In all SRS scenarios, bias in EBV attributable to differing
      flock genetic means rapidly decreased in the first 5 yr of sire referencing.
      Levels of bias did not substantially increase when flocks discontinued SRS after
      5 or 10 yr, suggesting that further participation in an SRS may not be necessary
      to manage risk. Natural service and noncontinuous SRS are viable options to
      continuous AI SRS in terms of genetic gain, inbreeding, and bias reduction.

PMID- 18073282
TI  - Nitrogen transactions along the gastrointestinal tract of cattle: A meta
      analytical approach.
AB  - In ruminant animals, endogenous N (EN) secretions contribute to meeting the N
      requirement of the ruminal microflora. The EN also constitutes a sizable portion
      of the duodenal N flow, which might be available to the host animal. Most
      measures of EN have been accomplished with highly invasive techniques or unusual
      semisynthetic diets. By utilizing a statistical approach and data obtained from
      studies reporting duodenal, ileal, and fecal N flows in cattle, the EN losses and
      true digestibility of N were estimated for different segments of the
      gastrointestinal tract of cattle. A simulation for a reference diet (24.2 g of
      N/kg of OM, 32% NDF and carbohydrates of medium fermentation rate) consumed at 2%
      of BW daily estimated that the minimal contribution of EN to the N available in
      the rumen was 39%. The free EN represented 13% of the duodenal N flow, and when
      bacterial N of EN origin was considered, EN contributed 35% of the total N flow.
      The minimal entry of EN into various segments of the gastrointestinal tract was
      also estimated as: foregut, 10.54; small intestine, 3.10; and hindgut, 5.0 g/kg
      of OMI. Rumen dietary N degradability was 0.68, and true N digestibilities in the
      small intestine and hindgut were 0.75 and 0.49, respectively. A better
      understanding of the factors involved in EN losses will allow for a more accurate
      estimation of both N supply and N requirements. This will translate into improved
      accuracy of diet formulation and less N excreted into the environment.

PMID- 18073283
TI  - The correlation of chemical and physical corn kernel traits with growth
      performance and carcass characteristics in pigs.
AB  - Corn kernel composition may affect its nutritive value and, thus, pig growth
      performance and carcass characteristics. The objective of this study was to
      determine the influence of the chemical and physical traits of corn kernels from
      different hybrids on the growth performance and carcass characteristics of pigs.
      A total of 288 crossbred pigs were grown in a 3-phase program from 21 kg of BW
      until slaughter at 113 kg of BW with 12 pens (4 pigs/pen) per dietary treatment.
      Target BW for each phase were 20 to 40 kg (grower 1), 40 to 80 kg (grower 2), and
      80 to 120 kg (finisher). In each phase, diets were formulated to be marginally
      deficient in Lys, TSAA, Ca, Na, and nonphytate P to improve the likelihood of
      detecting differences in performance due to corn hybrid. Each of 6 corn hybrids
      represented a wide range of kernel chemical and physical traits and was
      substituted for corn in a common diet formulation on an equal weight basis to
      make the 6 dietary treatments. Physical and chemical composition of the kernels
      were analyzed and correlated with performance measures by multivariate ANOVA.
      Kernel density was correlated with i.m. fat (IMF) content in LM (r = -.35, P <
      0.05). Stenvert grinding time was correlated (P < 0.05) with ADG during the
      grower 1 phase (r = 0.26), ADFI during the grower 2 phase (r = 0.27), final BW (r
      = 0.27), and IMF (r = -0.36). The amylose content of the cornstarch was
      correlated (P < 0.05) with ADG during the grower 2 phase (r = -0.28) and with BW
      at the end of the grower 2 phase (r = -0.27). The NDF content of the kernels was
      correlated (P < 0.05) with ADG during the finisher phase (r = -0.30), final BW (r
      = -0.33), and number of days to market (r = 0.31). The ADF content of the kernels
      was correlated (P < 0.05) with ADG during the grower 1 phase (r = -0.26), final
      BW (r = -0.26), and IMF (r = 0.31). The correlations of performance measure
      variation with individual kernel hybrid physical and chemical traits were
      statistically significant yet not large enough to base corn hybrid selection for
      feeding pigs on any single kernel chemical or physical trait.

PMID- 18073284
TI  - Digestible and metabolizable energy of crude glycerol for growing pigs.
AB  - The apparent DE and ME values of crude glycerol for growing pigs were determined
      in 5 experiments using crude glycerol (86.95% glycerol) from a biodiesel
      production facility, which used soybean oil as the initial feedstock. Dietary
      treatments were 0, 5, or 10% glycerol addition to basal diets in Exp. 1; 0, 5,
      10, or 20% glycerol addition to basal diets in Exp. 2; and 0 and 10% crude
      glycerol addition to the basal diets in Exp. 3, 4, and 5. Each diet was fed twice
      daily to pigs in individual metabolism crates. After a 10-d adjustment period, a
      5-d balance trial was conducted. During the collection period, feces and urine
      were collected separately after each meal and stored at 0 degrees C until
      analyses. The GE of each dietary treatment and samples of urine and feces from
      each pig were determined by isoperibol bomb calorimetry. Digestible energy of the
      diet was calculated by subtracting fecal energy from the GE in the feed, whereas
      ME was calculated by subtracting the urinary energy from DE. The DE and ME values
      of crude glycerol were estimated as the slope of the linear relationship between
      either DE or ME intake from the experimental diet and feed intake. Among all
      experiments, the crude glycerol (86.95% glycerol) examined in this study was
      shown to have a DE of 3,344 +/- 8 kcal/kg and an ME of 3,207 +/- 10 kcal/kg,
      thereby providing a highly available energy source for growing pigs.

PMID- 18073285
TI  - Genetic variability in Colombian Creole cattle populations estimated by pedigree
      information.
AB  - The genetic structure of 4 Colombian Creole cattle breeds, namely, Costeno con
      Cuernos, Blanco Orejinegro (BON), Romosinuano (ROMO), and Sanmartinero (SM), was
      studied with an analysis of the available pedigree data. The comparison between
      the effective number of founders (f(e)) and the effective number of ancestors
      (f(a)) revealed a decrease in the genetic variation that was rather important for
      the ROMO and San Martinero breeds, which had the lowest f(a)/f(e) ratios (0.34
      and 0.53, respectively). All breeds showed similar values for the number of
      equivalent generations traced, ranging from 3.1 in BON to 4.8 in ROMO. These 2
      populations also had the lowest and the highest population sizes, respectively.
      The lowest average inbreeding coefficient considering the whole pedigree was
      obtained by BON (0.18%), whereas the highest was attained by ROMO (1.22%).
      Finally, the percentage of individuals with an inbreeding level greater than
      6.25% in the reference population was high, indicating that the existing
      conservation management strategies could be improved to successfully maintain the
      genetic variability of these populations.

PMID- 18073286
TI  - Nonruminant nutrition symposium: understanding protein synthesis and degradation
      and their pathway regulations.

PMID- 18073287
TI  - Nonruminant nutrition symposium on natural phytobiotics for health of young
      animals and poultry: mechanisms and application.

PMID- 18073288
TI  - Effect of rumen-degradable protein balance deficit on voluntary intake, microbial
      protein synthesis, and nitrogen metabolism in growing double-muscled Belgian Blue
      bulls fed corn silage-based diet.
AB  - Two trials were conducted to evaluate the effect of rumen-degradable protein
      balance (OEB) deficit on voluntary intake (trial 1), microbial protein synthesis,
      and N metabolism (trial 2) in growing double-muscled Belgian Blue bulls. In trial
      1, six bulls (339 +/- 26 kg of initial BW) were used in a replicated 3 x 3 Latin
      square and received a diet of 60% corn silage and 40% concentrate with ad libitum
      intake (DM basis). Three concentrates were formulated by adding urea at the
      expense of barley to give similar dietary contents of intestinal digestible
      proteins, NE for fattening, and fermentable OM, but with different levels of OEB.
      Thus, 2 levels of OEB deficit (-23.7 and -9.2 g of OEB/kg of DM) were compared
      with a diet providing a slight OEB surplus (5.3 g of OEB/kg of DM). Voluntary DMI
      decreased linearly (P = 0.02) with decreasing rumen-degradable protein balance.
      This decrease in intake could explain the linear decrease in ADG observed when
      negative OEB diets were fed. In trial 2, six bulls (304 +/- 12 kg of initial BW)
      with cannulas in the rumen and proximal duodenum were used in a replicated 3 x 3
      Latin square and fed diets similar to those used in trial 1 at an intake level of
      85 g of DM/kg of BW(0.75). Diurnal variations of ruminal NH(3)-N and plasma urea
      N concentrations were greatly influenced by the level of OEB in the diet. No
      differences in NDF and starch degradation in the rumen, microbial N flow at the
      duodenum, or efficiency of microbial protein synthesis in the rumen were noted
      among the levels of OEB in diets. The reductions of the OEB value from 5.3 g/kg
      of DM to -9.2 g/ kg of DM and -23.7 g/kg of DM were associated with reductions of
      26.5 and 48.8% in urinary N output. Absolute amounts of N retained by the bulls
      increased significantly with the level of OEB in diets. Indeed, 51.4% of the
      incremental supply of N was excreted between -23.7 and -9.2 g of OEB/kg of DM
      diets, and 74.6% of the incremental supply of N was excreted between -9.2 and 5.3
      g of OEB/kg of DM diets. Feeding diets characterized by an adequate intestinal
      digestible protein supply and a OEB close to -10 g of OEB/kg of DM could be a
      feeding strategy to reduce N losses from the farm with little effect on the
      animal performance and voluntary intake. Reduced OEB may reduce N excretion in
      the environment but may also result in decreased N retention.

PMID- 18073289
TI  - Changes in rumen microbial fermentation are due to a combined effect of type of
      diet and pH.
AB  - Low ruminal pH may occur when feeding high-concentrate diets. However, because
      the reduction in pH occurs at the same time as the amount of concentrate fed
      increases, the changes observed in rumen fermentation may be attributed to pH or
      the type of substrate being fermented. Our objective was to determine the
      contribution of pH and type of substrate being fermented to the changes observed
      in rumen fermentation after supplying a high-concentrate diet. Eight dual-flow,
      continuous culture fermenters (1,400 mL) were used in 4 periods to study the
      effect of pH and type of diet being fermented on rumen microbial fermentation.
      Temperature (39 degrees C), solid (5%/h), and liquid (10%/h) dilution rates, and
      feeding schedule were maintained constant. Treatments were the type of diet (FOR
      = 60% ryegrass and alfalfa hays and 40% concentrate; CON = 10% straw and 90%
      concentrate) and pH (4.9, 5.2, 5.5, 5.8, 6.1, 6.4, 6.7, and 7.0). Diets were
      formulated to have similar CP and ruminally undegradable protein levels. Data
      were analyzed as a mixed-effects model considering the linear, quadratic, and
      cubic effects of pH, the effects of diet, and their interactions. Semipartial
      correlations of each independent variable were calculated to estimate the
      contribution of each factor to the overall relationship. True digestion of OM and
      NDF were affected by pH, but not by type of diet. Total VFA were reduced by pH
      and were greater in CON than in FOR. Acetate and butyrate concentrations were
      reduced by pH but were not affected by diet. Propionate concentration increased
      as the pH decreased and was greater in CON than in FOR. Ammonia-N concentration
      decreased with decreasing pH and was lower in CON than in FOR. Microbial N flow
      was affected by pH, diet, and their interaction. Dietary N flow increased as pH
      decreased and was greater in CON than in FOR. The degradation of CP followed the
      opposite pattern, increasing as pH increased, and was less in CON than in FOR.
      The efficiency of microbial protein synthesis (g of N/kg of OM truly digested)
      was slightly reduced by pH and was less in CON than in FOR. These results
      indicate that the effects of feeding a high-concentrate diet on rumen
      fermentation are due to a combination of pH and substrate. Furthermore, the
      digestion of OM in high-concentrate diets is likely limited by the pH-induced
      effects on the microbial population activity.

PMID- 18073290
TI  - Feeding distillers grains supplements to improve amino acid nutriture of lambs
      consuming moderate-quality forages.
AB  - We hypothesized that providing dried distillers grains with solubles (DDGS) would
      improve the N retention and use of nutrients by wethers fed a moderate-quality
      bromegrass hay. Additionally, we hypothesized that treatment effects on nutrient
      fluxes would be similar after 3, 6, or 9 wk on treatment. Chronic indwelling
      catheters were surgically implanted in a mesenteric artery, mesenteric vein,
      hepatic vein, and portal vein of 9 Suffolk x Dorset wethers (initial BW +/- SD =
      57.4 +/- 6.1 kg). Wethers had ad libitum access to moderate-quality bromegrass
      hay (8.44% CP, DM basis) and received 100 g/d of either a corn-based (Corn, n =
      4) or a DDGS-based (n = 5) supplement. There was no difference in DMI (P = 0.85)
      or DM digestibility (P = 0.46) between the 2 groups. There was a numerically
      greater N intake (21.5 vs. 18.4 g/d; P = 0.14) and N retention (4.4 vs. 2.5 g/d;
      P = 0.15) when wethers were supplemented with DDGS instead of Corn. Wethers fed
      DDGS had a greater (P = 0.008) release of alpha-amino N from the portal-drained
      viscera (PDV, 37.9 mmol/h) than those fed Corn (14.1 mmol/h). Similarly, there
      was a shift (P = 0.004) from a net splanchnic uptake to a net release of alpha
      amino N in wethers fed DDGS (9.1 mmol/h) compared with those fed Corn (-9.6
      mmol/h). However, there was no difference in ammonia release from the PDV (P =
      0.49) or hepatic release of urea-N (P = 0.19) between the 2 treatments. There
      were very limited interactions between nutrient fluxes and the length of time
      after the initiation of treatments. However, there was a tendency (interaction, P
      = 0.07) for the PDV release of alpha-amino N to be greater at 6 and 9 wk after
      the initiation of the treatments than after 3 wk on treatment for wethers fed
      DDGS, although there was no difference over time for wethers fed the Corn
      supplement. Additionally, there were changes in numerous nutrient fluxes between
      3 and 6 wk after the initiation of treatments regardless of treatment. These data
      indicate that DDGS is a viable supplement to enhance the nutriture of ruminants
      consuming moderate-quality forages. Additionally, these data indicate that the
      effects are discernible after 3 wk on treatment, with modest alterations in
      nutrient flux after additional time on treatment.

PMID- 18073291
TI  - Effects of dry cow treatment of beef cows on pathogenic organisms, milk somatic
      cell counts, and calf growth during the subsequent lactation.
AB  - Spring calving Angus and Angus x Hereford multiparous cows were utilized to
      determine the effects of intramammary treatment with penicillin G procaine
      (200,000 IU) and novobiocin (400 mg) at the time of weaning on udder health and
      calf growth after the subsequent calving. Cows were stratified by age and breed
      and assigned randomly to receive intramammary treatment (n = 99) at weaning or as
      untreated controls (n = 97). Quarter milk samples were collected at weaning and
      at 8 to 14 d after calving. Milk samples were analyzed for somatic cell counts
      (SCC) and mastitis-causing bacteria. Dry cow treatment decreased (P = 0.005) the
      number of cows infected after calving. Treatment decreased (P = 0.04) the number
      of cows that developed new infections and reduced (P = 0.03) the number of
      quarters with mastitis-causing bacteria after calving that were infected at
      weaning. Somatic cell counts after calving were greatest (P = 0.008) for cows
      infected with Staphylococcus aureus. Treatment did not alter (P = 0.19) SCC of
      quarters after calving that were infected with S. aureus at weaning but reduced
      (P = 0.002) SCC after calving of quarters that were infected with coagulase
      negative staphylococci at weaning. Body weight of calves during early lactation
      was increased (P = 0.006) if cows with intramammary infection were treated at
      weaning. Treatment of noninfected cows at weaning increased (P = 0.008) adjusted
      205-d weaning weights of calves after the subsequent lactation when compared with
      untreated noninfected cows. We conclude that treatment of beef cows at weaning
      with intramammary antibiotics decreased intramammary infections after calving,
      improved udder health during the subsequent lactation, and increased BW gain of
      the calves.

PMID- 18073292
TI  - Changes in connectedness over time in alternative sheep sire referencing schemes.
AB  - A statistic to measure the level of connectedness achieved among flocks would
      help producers to assess the risk of comparing EBV of animals from different
      flocks. The objectives of this research were to evaluate the pattern of change
      over time in selected connectedness measures and to determine how effectively
      these measures quantify the level of risk due to potential bias in EBV
      comparisons across production units. Connectedness was evaluated using simulated
      sheep populations, with connections established using sire referencing schemes
      (SRS). Pedigree and performance data for a single trait with a within-flock
      heritability of 0.25 were simulated (50 replications) for 15 flocks with 40 to
      140 ewes per flock. Genetic means for each flock were sampled from a normal
      distribution with mean 0 and SD equal to the trait's genetic SD. After 10 yr of
      random mating, flocks had opportunity to join a SRS and selection began for the
      simulated trait. Yearling rams were chosen as reference sires randomly from the
      top one-sixth of the population ranked on BLUP EBV. Every year, in each flock, 3
      reference sires were mated to 10 ewes each. Six sire referencing scenarios
      (including no SRS) and 2 sources of nonreference sires were simulated.
      Connectedness was measured in 2 ways: (i) as the average prediction error
      correlation (r(ij)) of the flock genetic means (flock r(ij)) or the EBV for the
      current crop of ram lambs (lamb r(ij)) or (ii) as the average scaled prediction
      error variance of differences (PEVD) in flock genetic means (flock PEVD) or in
      lamb EBV in the current crop of ram lambs (lamb PEVD). Flock r(ij) increased
      linearly in all scenarios while SRS was underway and leveled off if the flocks
      discontinued SRS. Lamb r(ij) increased rapidly as soon as SRS began but decreased
      substantially if the flocks discontinued SRS. Behavior of flock PEVD and lamb
      PEVD measures were similar but in the opposite direction (i.e., PEVD decreased
      with increasing r(ij)). Within scenarios, both flock r(ij) and flock PEVD had a
      nonlinear relationship with bias in comparing animals across flocks. However,
      only flock r(ij) exhibited a consistent relationship across simulation scenarios.
      When flock r(ij) reached 0.05 and 0.10, approximately 20 and 10%, respectively,
      of the bias due to initial differences in flock genetic means remained. These
      levels of flock r(ij) are suggested as benchmark levels for minimizing the risk
      of comparing animal EBV among units.

PMID- 18073293
TI  - Starting and advancing insulin for type 2 diabetes: algorithms and individualized
      methods are both necessary.

PMID- 18073294
TI  - Evaluation of [18F]fluoro-L-DOPA positron emission tomography-computed tomography
      for surgery in focal congenital hyperinsulinism.
AB  - CONTEXT: In congenital hyperinsulinism (CHI), the identification and precise
      localization of a focal lesion is essential for successful surgery. OBJECTIVE:
      Our objective was to evaluate the predictive value and accuracy of integrated
      [18F]fluoro-L-DOPA ([18F]FDOPA) positron emission tomography (PET)-computed
      tomography (CT) for the surgical therapy of CHI. DESIGN: This was an
      observational study. SETTING: The study was performed in the Department of
      Pediatric Surgery at a university hospital. PATIENTS: From February 2005 to
      September 2007, 10 children with the clinical signs of CHI and an increased
      radiotracer uptake in a circumscribed area of the pancreas in the [18F]FDOPA PET
      CT were evaluated. INTERVENTIONS: Guided by the [18F]FDOPA PET-CT report, all
      children underwent partial pancreatic resection, in two cases twice. MAIN OUTCOME
      MEASURES: Correlation of the anatomical findings at surgery with the report of
      the [18F]FDOPA PET-CT, and the results of surgery and clinical outcome were
      determined. RESULTS: In nine children the intraoperative situation corresponded
      exactly to the description of the [18F]FDOPA PET-CT. A limited resection of the
      pancreas was curative in eight cases at the first surgery, in one case at the
      second intervention. We observed no diabetes mellitus or exocrine insufficiency
      in the follow up so far. In one child, hypoglycemia persisted even after two
      partial resections of the pancreatic head. Histological analysis finally revealed
      an atypical intermediate form of CHI. CONCLUSIONS: The integrated [18F]FDOPA PET
      CT is accurate to localize the lesion in focal CHI and is a valuable tool to
      guide the surgeon in limited pancreatic resection.

PMID- 18073295
TI  - Growth hormone (GH) insensitivity and insulin-like growth factor-I deficiency in
      Inuit subjects and an Ecuadorian cohort: functional studies of two codon 180 GH
      receptor gene mutations.
AB  - CONTEXT: Among more than 250 cases of GH insensitivity syndrome (GHIS) reported
      to date, the largest cohort was identified in southern Ecuador. In the Ecuadorian
      GHIS cohort, a sense mutation (GAA>GAG) at codon E180 of GH receptor [GHR
      (E180sp)] results in deletion of codons 181-188. No functional studies of this
      mutation have been performed, nor have different mutations at codon 180 been
      reported. OBJECTIVE: We now report identification of a novel GHR mutation, also
      within codon E180, in two distantly related GHIS subjects of Inuit origin and
      provide mechanistic insights into the defects caused by the Inuit and Ecuadorian
      GHR mutations. PATIENTS: The two Inuit subjects, with heights of -5 sd score and 
      7 sd score, respectively, had elevated circulating levels of GH but low levels of
      GH-binding protein, IGF-I, and IGF-binding protein-3. RESULTS: Both Inuit
      subjects carry the same novel nonsense homozygous GHR mutation at codon E180 (GAA
      >TAA, E180X). In vitro reconstitution experiments demonstrated that GHR (E180sp),
      but not GHR (E180X), could be stably expressed. GHR (E180sp), however, could not
      bind GH and could neither activate signal transducer and activator of
      transcription-5b nor induce -5b-dependent gene expression on GH treatment.
      Furthermore, the GHR (E180sp), which has a deletion of eight amino acid residues
      within the GHR dimerization domain, although retaining the ability to
      homodimerize, was defective in trafficking to the cell surface. CONCLUSIONS: The
      E180X mutation identified in two Inuit patients resulted in a truncated, unstably
      expressed GHR variant, whereas the E180 splicing mutation previously identified
      in the Ecuadorian cohort, affected both GH binding and GHR trafficking and
      rendered the abnormal GHR nonfunctional.

PMID- 18073296
TI  - The increasing prevalence of metabolic syndrome among Finnish men and women over
      a decade.
AB  - OBJECTIVE: Our objective was to assess a 10-yr change in the prevalence of the
      metabolic syndrome defined by the National Cholesterol Education Program (NCEP)
      and the International Diabetes Federation (IDF) among Finnish men and women.
      DESIGN AND SUBJECTS: Two cross-sectional population surveys were performed in
      Finland in 1992 and 2002. A total of 3495 participants aged 45-64 yr were
      included in the analysis. RESULTS: In both years the metabolic syndrome was more
      common among men than women. In men the prevalence of the metabolic syndrome
      tended to increase slightly between 1992 and 2002, from 48.8-52.6% (P=0.139)
      based on the NCEP definition, and from 51.4-55.6% based on the IDF definition
      (P=0.102). In women the prevalence of the metabolic syndrome increased
      significantly from 32.2-39.1% based on the NCEP definition (P=0.003), and from
      38.0-45.3% based on the IDF definition (P=0.002). In both sexes the prevalence of
      high blood pressure decreased, but the abnormalities in glucose metabolism
      increased between 1992 and 2002. The prevalence of central obesity increased in
      women between 1992 and 2002. CONCLUSIONS: In Finland the prevalence of the
      metabolic syndrome, based both on the NCEP and IDF definitions, is higher in men
      than women. However, the increase in the prevalence of the metabolic syndrome,
      from 1992-2002, was significant only among women.

PMID- 18073298
TI  - The association between hyperglycemia and fracture risk in middle age. A
      prospective, population-based study of 22,444 men and 10,902 women.
AB  - AIMS: Type 1 diabetes mellitus is associated with increased fracture risk,
      whereas the risk associated with type 2 diabetes is less obvious. Elevated
      fasting blood glucose and high 2-h glucose during an oral glucose tolerance test
      indicate impaired glucose tolerance or diabetes. The associations among fasting
      blood glucose, 2-h glucose, and the risk of fracture were investigated. METHODS:
      The Malmo Preventive Project consists of 22,444 men (44+/-6.6 yr) and 10,902
      women (50+/-7.4 yr), with a follow-up of 19 yr (+/-3.9) and 15 yr (+/-4.5) for
      incident fractures. Baseline assessment included multiple examinations and
      lifestyle information. A logistic regression model was used. Adjustments were
      made for age, body mass index (BMI), and smoking. RESULTS: Low-energy fractures
      were recorded in 1246 men and 1236 women. A 2-h glucose measurement between 4.3
      and 6.2 mmol/liter in men (second and third quartile), and above 6.5 mmol/liter
      in women (third and fourth quartile), adjusted for age, BMI, and smoking, was
      significantly associated with a decreased risk of multiple fractures, in men
      [odds ratios (ORs) 0.57-0.71] and women (ORs 0.38-0.66). In women, a 2-h glucose
      measurement above 7.5 mmol/liter was associated with a decreased risk of
      osteoporotic fractures (OR 0.57, 95% confidence interval 0.44-0.74). CONCLUSIONS:
      In middle-aged men and women, elevated 2-h glucose levels were associated with
      decreased risks of multiple and osteoporotic fractures, independent of age, BMI,
      and smoking. A high 2-h glucose level is characterized by peripheral insulin
      resistance with a high insulin level. Our findings indirectly suggest a positive
      effect on bone from hyperglycemia.

PMID- 18073297
TI  - The G53D mutation in Kir6.2 (KCNJ11) is associated with neonatal diabetes and
      motor dysfunction in adulthood that is improved with sulfonylurea therapy.
AB  - CONTEXT: Mutations in the Kir6.2 subunit (KCNJ11) of the ATP-sensitive potassium
      channel (KATP) underlie neonatal diabetes mellitus. In severe cases, Kir6.2
      mutations underlie developmental delay, epilepsy, and neonatal diabetes (DEND).
      All Kir6.2 mutations examined decrease the ATP inhibition of KATP, which is
      predicted to suppress electrical activity in neurons (peripheral and central),
      muscle, and pancreas. Inhibitory sulfonylureas (SUs) have been used successfully
      to treat diabetes in patients with activating Kir6.2 mutations. There are two
      reports of improved neurological features in SU-treated DEND patients but no
      report of such improvement in adulthood. OBJECTIVE: The objective of the study
      was to determine the molecular basis of intermediate DEND in a 27-yr-old patient
      with a KCNJ11 mutation (G53D) and the patient's response to SU therapy. DESIGN:
      The G53D patient was transferred from insulin to gliclazide and then to
      glibenclamide over a 160-d period. Motor function was assessed throughout.
      Electrophysiology assessed the effect of the G53D mutation on KATP activity.
      RESULTS: The G53D patient demonstrated improved glycemic control and motor
      coordination with SU treatment, although glibenclamide was more effective than
      gliclazide. Reconstituted G53D channels exhibit reduced ATP sensitivity, which is
      predicted to suppress electrical activity in vivo. G53D channels coexpressed with
      SUR1 (the pancreatic and neuronal isoform) exhibit high-affinity block by
      gliclazide but are insensitive to block when coexpressed with SUR2A (the skeletal
      muscle isoform). High-affinity block by glibenclamide is present in G53D channels
      coexpressed with either SUR1 or SUR2A. CONCLUSION: The results demonstrate that
      SUs can resolve motor dysfunction in an adult with intermediate DEND and that
      this improvement is due to inhibition of the neuronal but not skeletal muscle
      KATP.

PMID- 18073299
TI  - Protein kinase A-independent inhibition of proliferation and induction of
      apoptosis in human thyroid cancer cells by 8-Cl-adenosine.
AB  - PURPOSE: Protein kinase A (PKA) affects cell proliferation in many cell types and
      is a potential target for cancer treatment. PKA activity is stimulated by cAMP
      and cAMP analogs. One such substance, 8-Cl-cAMP, and its metabolite 8-Cl
      adenosine (8-Cl-ADO) are known inhibitors of cancer cell proliferation; however,
      their mechanism of action is controversial. We have investigated the
      antiproliferative effects of 8-Cl-cAMP and 8-CL-ADO on human thyroid cancer cells
      and determined PKA's involvement. EXPERIMENTAL DESIGN: We employed proliferation
      and apoptosis assays and PKA activity and cell cycle analysis to understand the
      effect of 8-Cl-ADO and 8-Cl-cAMP on human thyroid cancer and HeLa cell lines.
      RESULTS: 8-Cl-ADO inhibited proliferation of all cells, an effect that lasted for
      at least 4 d. Proliferation was also inhibited by 8-Cl-cAMP, but this inhibition
      was reduced by 3-isobutyl-1-methylxanthine; both drugs stimulated apoptosis, and
      3-isobutyl-1-methylxanthine drastically reduced 8-Cl-cAMP-induced cell death. 8
      Cl-ADO induced cell accumulation in G1/S or G2/M cell cycle phases and
      differentially altered PKA activity and subunit levels. PKA stimulation or
      inhibition and adenosine receptor agonists or antagonists did not significantly
      affect proliferation. CONCLUSIONS: 8-Cl-ADO and 8-Cl-cAMP inhibit proliferation,
      induce cell cycle phase accumulation, and stimulate apoptosis in thyroid cancer
      cells. The effect of 8-Cl-cAMP is likely due to its metabolite 8-Cl-ADO, and PKA
      does not appear to have direct involvement in the inhibition of proliferation by
      8-Cl-ADO. 8-Cl-ADO may be a useful therapeutic agent to be explored in aggressive
      thyroid cancer.

PMID- 18073300
TI  - Interleukin (IL)-23 receptor is a major susceptibility gene for Graves'
      ophthalmopathy: the IL-23/T-helper 17 axis extends to thyroid autoimmunity.
AB  - CONTEXT: IL-23 and its receptor (IL-23R) guide T cells toward the T-helper 17
      phenotype. IL-23R single nucleotide polymorphisms (SNPs) have been associated
      with several autoimmune diseases, including Crohn's disease and rheumatoid
      arthritis. OBJECTIVE: Our objective was to determine whether variants in the IL
      23R gene are associated with Graves' disease (GD) and Graves' ophthalmopathy
      (GO). DESIGN AND PARTICIPANTS: A total of 216 North American Caucasian GD
      patients and 368 healthy controls were genotyped for four SNPs spanning the IL
      23R gene. SNPs rs11209026 and rs7530511 were genotyped using the TaqMan allelic
      discrimination assays (Applied Biosystems, Foster City, CA), and SNPs rs2201841
      and rs10889677 were genotyped using a fluorescent-based restriction fragment
      length polymorphism method. RESULTS: The A allele of rs2201841 was present in
      78.8% of GD patients with GO and 64.7% of controls [P=1.1x10(-4); odds ratio
      (OR)=2.04]; the AA genotype was also significantly increased in GO patients
      compared with controls (62.5 and 41%, respectively; P=1.0x10(-4); OR=2.4). The C
      allele of rs10889677 was present in 78.6% of GO patients and 64.5% of controls
      (P=1.3x10(-4); OR=2.03), and the CC genotype was also significantly increased in
      GO patients vs. controls (62.1 and 41.0%, respectively; P=1.4x10(-4); OR=2.36).
      The TT genotype of rs7530511 was significantly associated with GD, but not
      specifically with GO; it was present in 2.5% of GD patients and 0.3% of controls
      (P=0.02; OR=9.4). The rs11209026 SNP, which is the most strongly associated with
      Crohn's disease, was not associated with GD or GO in our data set. CONCLUSIONS:
      Variants in the IL-23R gene are strongly associated with GO. These variants may
      predispose to GO by changing the expression and/or function of IL-23R, thereby
      promoting a proinflammatory signaling cascade.

PMID- 18073301
TI  - Inhibition of luteinizing hormone secretion by testosterone in men requires
      aromatization for its pituitary but not its hypothalamic effects: evidence from
      the tandem study of normal and gonadotropin-releasing hormone-deficient men.
AB  - CONTEXT: Studies on the regulation of LH secretion by sex steroids in men are
      conflicting. OBJECTIVE: Our aims were to determine the relative contributions of
      testosterone (T) and estradiol (E2) to LH regulation and localize their sites of
      negative feedback. DESIGN: This was a prospective study with three arms. SETTING:
      The study was conducted at a General Clinical Research Center. PATIENTS OR OTHER
      PARTICIPANTS: Twenty-two normal (NL) men and 11 men with GnRH deficiency due to
      idiopathic hypogonadotropic hypogonadism (IHH) participated. INTERVENTION:
      Medical castration and inhibition of aromatase were achieved using high-dose
      ketoconazole (KC) for 7 d with 1) no sex steroid add-back; 2) T enanthate 125 mg
      im starting on d 4; or 3) E2 patch 37.5 microg/d starting on d 4. Blood sampling
      was performed every 10 min for 12 h at baseline, overnight on d 3-4 and d 6-7.
      MAIN OUTCOME MEASURES: Mean LH levels, LH pulse amplitude, and GnRH pulse
      frequency were assessed at baseline, d 3-4, and d 6-7. RESULTS: In NL men, KC
      caused a 3-fold increase in mean LH on d 3-4, which was stable on d 6-7 with no
      add-back. Addition of T reduced LH levels (34.6+/-3.9 to 17.4+/-3.6 IU/liter,
      P<0.05) by slowing GnRH pulse frequency (13.3+/-0.4 to 6.7+/-1.0 pulses/12 h,
      P<0.005). LH amplitude increased (6.9+/-1.0 to 12.1+/-1.4 IU/liter, P<0.005). E2
      add-back suppressed LH levels (36.4+/-5.6 to 19.0+/-2.4 IU/liter, P<0.005), by
      slowing GnRH pulse frequency (11.4+/-0.2 to 8.6+/-0.4 pulses/12 h, P<0.05) and
      had no impact on LH pulse amplitude. In IHH men, restoring normal T levels caused
      no suppression of mean LH levels or LH amplitude. E2 add-back normalized mean LH
      levels and decreased LH amplitude from 14.7+/-1.7 to 12+/-1.5 IU/liter (P<0.05).
      CONCLUSIONS: 1) T and E2 have independent effects on LH. 2) Inhibition of LH by T
      requires aromatization for its pituitary, but not hypothalamic effects. 3) E2
      negative feedback on LH occurs at the hypothalamus.

PMID- 18073302
TI  - Dehydroepiandrosterone sulfate levels are associated with more favorable
      cognitive function in women.
AB  - CONTEXT: It has been proposed that dehydroepiandrosterone and
      dehydroepiandrosterone sulfate (DHEAS) exert neuroprotective effects in the
      brain, yet evidence of associations between the endogenous levels of these
      steroids and measures of cognitive function is lacking. OBJECTIVE: The objective
      of the study was to investigate whether circulating levels of DHEAS independently
      contribute to aspects of cognitive function in women in the community. DESIGN:
      This was a community-based, cross-sectional study. SETTING AND PARTICIPANTS: Two
      hundred ninety-five women, aged 21-77 yr, were recruited from a community-based
      data set and participated between September 2003 and December 2004. Women were
      excluded if they reported any health condition that might potentially adversely
      affect cognitive function. MAIN OUTCOME MEASURES: The individual scores of a
      comprehensive battery of tests of cognitive function and the serum level of DHEAS
      (square root transformed) were measured. RESULTS: In the multiple linear
      regression analysis, the DHEAS term made a significant independent positive
      contribution to the Controlled Oral Word Association Test score, a measure of
      executive function. In addition, women with a DHEAS level in the highest tertile
      who also had more than 12 yr of education performed better on both Digit Span
      Forward and Digit Span Backward tests, which are tests of simple concentration
      and working memory, respectively. CONCLUSIONS: Higher endogenous DHEAS levels are
      independently and favorably associated with executive function, concentration,
      and working memory.

PMID- 18073303
TI  - Antithyroperoxidase antibody-dependent cytotoxicity in autoimmune thyroid
      disease.
AB  - CONTEXT: Thyroid antibody-dependent cytotoxicity has been reported in autoimmune
      thyroid disease (AITD). Indeed, the role of thyroperoxidase (TPO) autoantibodies
      (aAbs) in complement-mediated damage by binding to TPO expressed on the surface
      of human thyroid cells was demonstrated, whereas their activity in antibody
      dependent cell cytotoxicity (ADCC) is not well established. OBJECTIVE: The aim of
      this study was to define the partners involved in antibody and complement
      dependent cytotoxicity (CDC) in AITD and characterize which effector cells are
      involved in cytotoxicity mediated by anti-TPO aAbs using a chromium release
      assay. RESULTS: The relative capability of anti-TPO aAbs to mediate ADCC using
      human thyroid cells in culture varies from 11 to 74.5%, depending on the
      effectors cells used. The human monocyte cell line HL60 gives a better lysis than
      the THP-1 cell line as effector cells. It seems obvious that the mechanism of
      ADCC is mediated quite exclusively by FcgammaRI. Indeed, the two effector cell
      lines differ by the level of the FcgammaRI expression (91.83% for HL-60 cells and
      22.55%t for the THP-1). In addition to ADCC, the anti-TPO aAbs mediate the
      destruction of thyrocytes by CDC (56%). CONCLUSIONS: These results demonstrate
      that anti-TPO aAbs can damage cultured thyroid cells by ADCC and CDC mechanisms.
      The monocytes, via their FcgammaRI, are important effector cells in ADCC mediated
      by anti-TPO aAbs and may contribute with T cells to the destruction of thyroid
      gland in AITD.

PMID- 18073304
TI  - The leucine-rich repeat-containing G protein-coupled receptor 8 gene T222P
      mutation does not cause cryptorchidism.
AB  - CONTEXT: Insulin-like 3 and its receptor, leucine-rich repeat-containing G
      protein-coupled receptor 8 (LGR8), are essential for the first phase of
      testicular descent. Homozygous loss of either of the two genes in mice leads to
      cryptorchidism. Although mutations in both homologous human genes are not a
      common cause of cryptorchidism. To date, only one missense mutation at codon 222
      (T222P) of the LGR8 gene has been proposed as a causative mutation for
      cryptorchidism. This conclusion was based on both functional in vitro studies and
      the lack of mutation in a large group of controls. The geographical origin of the
      mutation carriers suggested a founder effect in the Mediterranean area.
      OBJECTIVES: We sought to define the frequency of the T222P mutation in four
      different countries to assess whether the screening for this mutation could be of
      use as a diagnostic genetic test. MATERIALS AND METHODS: A total of 822 subjects
      (359 with a history of cryptorchidism and 463 controls) from Italy, Spain,
      Hungary, and Egypt were genotyped for the T222P mutation by direct sequencing.
      RESULTS: The phenotypical expression of the mutation also included normal
      testicular descent. The mutation frequency was not significantly different in
      cryptorchid patients vs. noncryptorchid controls (3.6 vs. 1.7%, respectively). No
      significant geographical differences were observed in mutation frequencies. The
      haplotype analysis allowed us to predict three distinct haplotypes, i.e. three
      possible mutation events. CONCLUSIONS: Our results suggest that the T222P
      mutation cannot be considered either causative or a susceptibility factor for
      cryptorchidism. A true causative mutation in the LGR8 gene still remains to be
      identified.

PMID- 18073305
TI  - Thyroid function and lipid subparticle sizes in patients with short-term
      hypothyroidism and a population-based cohort.
AB  - CONTEXT: Relations between thyroid function and lipids remain incompletely
      understood. OBJECTIVE: Our objective was to determine whether lipoprotein
      subparticle concentrations are associated with thyroid status. DESIGN AND
      SETTING: We conducted a prospective clinical study and cross-sectional cohort
      analysis at a university endocrine clinic and the Framingham Heart Study.
      SUBJECTS: Subjects included 28 thyroidectomized patients with short-term overt
      hypothyroidism and 2944 Framingham Offspring cohort participants. MAIN OUTCOME
      MEASURES: Fasting subclass concentrations of very-low-density lipoprotein (VLDL),
      intermediate-density lipoprotein, low-density lipoprotein cholesterol (LDL-C),
      and high-density lipoprotein cholesterol (HDL-C) particles were measured by
      nuclear magnetic resonance spectroscopy. TSH values were also measured. RESULTS:
      Total cholesterol and LDL-C were increased during short-term overt
      hypothyroidism. Large LDL subparticle concentrations increased during
      hypothyroidism (917+/-294 vs. 491+/-183 nmol/liter; P<0.001), but more
      atherogenic small LDL was unchanged. Triglycerides marginally increased during
      hypothyroidism, small VLDL particles significantly increased (P<0.001), whereas
      more atherogenic large VLDL was unchanged. Total HDL-C increased during
      hypothyroidism (76+/-13 mg/dl vs. 58+/-15 mg/dl; P<0.001). There was no change in
      large HDL-C particle concentrations, whereas small (P<0.001) and medium (P=0.002)
      HDL-C particle concentrations decreased. Among Framingham women, adjusted total
      cholesterol and LDL-C were positively related to TSH categories (P<or=0.003).
      This was due to a positive correlation between adjusted large LDL subparticle
      concentrations and log-TSH (P<0.0001); log small LDL subparticle concentrations
      decreased slightly as log-TSH increased (P=0.045). Among Framingham men, the only
      significant association was a positive association between log-TSH and log large
      HDL subparticle concentrations (P=0.04). CONCLUSIONS: There is a shift toward
      less atherogenic large LDL, small VLDL, and large HDL subparticle sizes in
      hypothyroid women.

PMID- 18073306
TI  - Ultrasound measurement of median and ulnar nerve cross-sectional area in
      acromegaly.
AB  - CONTEXT: Acromegalic patients may complain of sensory disturbances in their
      hands. OBJECTIVE: Our objective was to examine median (MN) and ulnar nerves (UN)
      of acromegalic patients with ultrasound (US) and to determine whether nerve
      abnormalities correlate with clinical parameters and nerve conduction studies
      (NCS). PATIENTS: We prospectively examined the MN and UN in 34 nondiabetic,
      acromegalic patients (18 females and 16 males; age range 18-79 yr) and 34 sex-,
      age-, and body mass index-matched controls with 17-5 MHz US. INTERVENTION: The MN
      was examined at the carpal tunnel (MN-Ct) and at mid-forearm (MN-f) levels; the
      UN at the mid-forearm (UN-f) and distal arm (UN-a). A total of 272 nerve cross
      sectional areas (CSA) were recorded from both patients and controls. In addition,
      22 patients underwent NCS. RESULTS: Nerves of acromegalic patients (MN-Ct=16.5+/
      4.4 mm2; MN-f=10.5+/-2.4 mm2; UN-f=9.5+/-3.0 mm2; UN-a=13.1+/-3.7 mm2) had
      significantly (P<0.0001) greater CSA compared with controls (MN-Ct=7.4+/-1.7 mm2;
      MN-f=5.5+/-1.4 mm2; UN-f=5.3+/-1.4 mm2; UN-a=6.6+/-1.7 mm2). NCS displayed at
      least one abnormality in 59% of patients. Acromegalic patients, grouped according
      to disease activity (14 controlled, 8 partially controlled, 12 uncontrolled), had
      significantly (P<0.0001) greater CSA compared with controls. Nerve CSA were
      significantly greater in uncontrolled patients compared to controlled, both at MN
      Ct and at UN-f levels (P<0.01). Abnormal NCS were observed in five of seven
      uncontrolled patients and four of nine controlled patients. IGF-I levels, but not
      GH levels, were correlated with CSA (r=0.34), whereas disease duration correlated
      with both nerve CSA and NCS (r=0.33 and r=0.31). CONCLUSION: US identified a
      significantly increased volume of MN and UN in acromegalic patients. Peripheral
      nerve enlargement in acromegaly seems to be an intrinsic feature of the disease
      related to clinical control, disease duration, and IGF-I levels.

PMID- 18073307
TI  - Prognostic significance of somatic RET oncogene mutations in sporadic medullary
      thyroid cancer: a 10-year follow-up study.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) is a well-differentiated thyroid
      tumor that maintains the typical features of C cells. An advanced stage and the
      presence of lymph node metastases at diagnosis have been demonstrated to be the
      most important bad prognostic factors. Somatic RET mutations have been found in
      40-50% of MTCs. Although a relationship between somatic mutations and bad
      prognosis has been described, data are controversial and have been performed in
      small series with short-term follow ups. The aim of this study was to verify the
      prognostic value of somatic RET mutations in a large series of MTCs with a long
      follow up. METHODS: We studied 100 sporadic MTC patients with a 10.2 yr mean
      follow-up. RET gene exons 10-11 and 13-16 were analyzed. The correlation between
      the presence/absence of a somatic RET mutation, clinical/pathological features,
      and outcome of MTC patients was evaluated. RESULTS: A somatic RET mutation was
      found in 43 of 100 (43%) sporadic MTCs. The most frequent mutation (34 of 43,
      79%) was M918T. RET mutation occurrence was more frequent in larger tumors
      (P=0.03), and in MTC with node and distant metastases (P<0.0001 and P=0.02,
      respectively), thus, a significant correlation was found with a more advanced
      stage at diagnosis (P=0.004). A worse outcome was also significantly correlated
      with the presence of a somatic RET mutation (P=0.002). Among all prognostic
      factors found to be correlated with a worse outcome, at multivariate analysis
      only the advanced stage at diagnosis and the presence of a RET mutation showed an
      independent correlation (P<0.0001 and P=0.01, respectively). Finally, the
      survival curves of MTC patients showed a significantly lower percentage of
      surviving patients in the group with RET mutations (P=0.006). CONCLUSIONS: We
      demonstrated that the presence of a somatic RET mutation correlates with a worse
      outcome of MTC patients, not only for the highest probability to have persistence
      of the disease, but also for a lower survival rate in a long-term follow up. More
      interestingly, the presence of a somatic RET mutation correlates with the
      presence of lymph node metastases at diagnosis, which is a known bad prognostic
      factor for the definitive cure of MTC patients.

PMID- 18073308
TI  - Granulosa cell survival and proliferation are altered in polycystic ovary
      syndrome.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) represents the most common endocrine
      abnormality in women of reproductive age. The cause of PCOS remains largely
      unknown, but studies suggest an intrinsic ovarian abnormality. OBJECTIVE: The
      objective of the study was to test our hypothesis that differences in granulosa
      cell proliferation and apoptosis may underlie abnormalities that affect
      follicular development. DESIGN: Granulosa cells were prepared from follicular
      fluid aspirated from 4- to 8-mm follicles of unstimulated ovaries during routine
      laparoscopy or laparotomy from women with anovulatory PCOS and those with regular
      ovulatory cycles. SETTING: The study was conducted at a university hospital.
      PATIENTS: Fourteen women with anovulatory PCOS and nine women with regular
      ovulatory cycles participated in the study. MAIN OUTCOME MEASURES:
      Immunocytochemistry on granulosa cells to investigate apoptotic and proliferation
      rates, together with real-time RT-PCR to analyze gene expression profiles of
      apoptotic regulators, was measured. RESULTS: Significantly lower apoptotic rates
      were found in granulosa cells from patients with PCOS, compared with women with
      regular ovulatory cycles (P=0.004). Lower apoptotic rates were associated with
      decreased levels of the apoptotic effector caspase-3 (P=0.001) and increased
      levels of the anti-apoptotic survival factor cellular inhibitor of apoptosis
      proteins-2 in the PCOS group that were coupled to higher proliferation rates
      (P=0.032). Gene expression profiling confirmed the immunocytochemical findings.
      CONCLUSIONS: Our findings indicate that there are significant differences in the
      rate of cell death and proliferation in granulosa cell populations in PCOS
      patients. These are associated with decreased expression of apoptotic effectors
      and increased expression of a cell survival factor. These results provide new
      insights that may be useful in developing specific therapeutic intervention
      strategies in PCOS.

PMID- 18073309
TI  - The role of the receptor activator of nuclear factor-kappaB
      ligand/osteoprotegerin cytokine system in primary hyperparathyroidism.
AB  - CONTEXT: The mechanisms of action of PTH on bone in vivo remain incompletely
      understood. The objective of this investigation was to examine changes in serum
      levels of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin
      (OPG) in primary hyperparathyroidism and their relationship to bone loss.
      PATIENTS AND METHODS: Twenty-nine patients with primary hyperparathyroidism had
      baseline circulating soluble receptor activator of nuclear factor-kappaB ligand
      (sRANKL) and OPG measured. The relationship to biochemical markers of bone
      turnover and changes in bone mineral density over 2 yr was examined. RESULTS:
      Baseline sRANKL levels were elevated (1.7+/-0.1 pmol/liter), whereas OPG remained
      in the normal range (5.6+/-0.4 pmol/liter). Circulating sRANKL did not correlate
      with PTH but did correlate with markers of bone resorption (urine
      deoxypyridinoline cross-links: r=0.51, P<0.01; serum N-telopeptide of type I
      collagen: r=0.37, P<0.05). Furthermore, sRANKL correlated with both IL-6 and IL-6
      soluble receptor (IL-6sR) (r=0.47, P<0.05 and r=0.55, P<0.005, respectively).
      Serum sRANKL levels also correlated with bone loss at the total femur (r=-0.53,
      P<0.01). Lastly, a high value of sRANKL in combination with values of IL-6 and IL
      6sR in the upper quartile (sRANKL>or=1.81 pg/ml, IL -6>or=11.8 pg/ml, and IL
      6sR>or=45.6 ng/ml) defined a group of four women with significantly greater rates
      of bone loss at the total femur than the remaining patients (-2.7+/-1.7% vs.
      +0.5+/-0.3%; n=4 vs. n=19, P<0.05). CONCLUSION: Determination of circulating
      levels of sRANKL may be useful in identifying patients with mild primary
      hyperparathyroidism at greater risk for bone loss. The fact that circulating
      sRANKL did not correlate with PTH but did correlate with markers of bone
      resorption suggests that skeletal responsiveness to PTH may differ in this
      disease.

PMID- 18073310
TI  - Serological evidence of thyroid autoimmunity among schoolchildren in two
      different socioeconomic environments.
AB  - CONTEXT: The mechanisms leading to thyroid autoimmunity are largely unknown.
      OBJECTIVE: Our objective was to assess the role of environment in the development
      of thyroid autoimmunity. DESIGN: Prevalence of thyroid autoantibodies in two
      neighboring populations living in completely different socioeconomic
      circumstances (Russian Karelia and Finland) was studied. SETTING: We studied two
      population-based cohorts partly sharing the same ancestry. PATIENTS OR OTHER
      PARTICIPANTS: A total of 532 schoolchildren from Russian Karelia and 532
      schoolchildren in Finland matched for age, gender, and season of the blood
      sampling were included. INTERVENTIONS: There were no interventions. MAIN OUTCOME
      MEASURES: The prevalence of thyroid peroxidase antibodies (TPOAb), thyroglobulin
      antibodies (TGAb) and HLA-DQ alleles was measured. RESULTS: The prevalence of
      TPOAb was significantly lower in Russian Karelian than in Finnish children (0.4
      vs. 2.6%, P=0.006). A similar difference was observed for TGAb (0.6 vs. 3.4%,
      P=0.002). Finnish girls tested positive for both TPOAb (4.3 vs. 0.4%, P=0.01) and
      TGAb (5.3 vs. 0.9%, P=0.01) more frequently than Finnish boys. Seven of the 23
      tested subjects with signs of thyroid autoimmunity (30%) had increased serum TSH
      concentrations as a sign of subclinical hypothyroidism. The frequency of HLA
      genotypes did not differ between the two countries or between autoantibody
      positive and -negative subjects. CONCLUSIONS: The prevalence of thyroid
      autoimmunity is lower in Russian Karelia than in Finland. This difference was not
      related to ethnic background or HLA-DQ alleles. The results support the idea that
      the Russian Karelian environment, which is characterized by inferior prosperity
      and standard of hygiene, may provide protection against thyroid autoimmunity.

PMID- 18073311
TI  - Three novel missense mutations within the LHX4 gene are associated with variable
      pituitary hormone deficiencies.
AB  - CONTEXT: The LHX4 LIM-homeodomain transcription factor has essential roles in
      pituitary gland and nervous system development. Heterozygous mutations in LHX4
      are associated with combined pituitary hormone deficiency. OBJECTIVES: Our
      objectives were to determine the nature and frequency of LHX4 mutations in
      patients with pituitary hormone deficiency and to examine the functional outcomes
      of observed mutations. DESIGN: The LHX4 gene sequence was determined from patient
      DNA. The biochemical and gene regulatory properties of aberrant LHX4 proteins
      were characterized using structural predictions, pituitary gene transcription
      assays, and DNA binding experiments. PATIENTS: A total of 253 patients from 245
      pedigrees with GH deficiency and deficiency of at least one additional pituitary
      hormone was included in the study. RESULTS: In five patients, three types of
      heterozygous missense mutations in LHX4 that result in substitution of conserved
      amino acids were identified. One substitution is between the LIM domains (R84C);
      the others are in the homeodomain (L190R; A210P). The patients have GH
      deficiency; some also display reductions in TSH, LH, FSH, or ACTH, and aberrant
      pituitary morphology. Structural models predict that the aberrant L190R and A210P
      LHX4 proteins would have impaired DNA binding and gene activation properties.
      Consistent with these models, EMSAs and transfection experiments using pituitary
      gene promoters demonstrate that whereas the R84C form has reduced activity, the
      L190R and A210P proteins are inactive. CONCLUSIONS: LHX4 mutations are a
      relatively rare cause of combined pituitary hormone deficiency. This report
      extends the range of phenotypes associated with LHX4 gene mutations and describes
      three novel exonic mutations in the gene.

PMID- 18073312
TI  - Short-term aerobic exercise training in obese humans with type 2 diabetes
      mellitus improves whole-body insulin sensitivity through gains in peripheral, not
      hepatic insulin sensitivity.
AB  - CONTEXT: Short-term aerobic exercise training can improve whole-body insulin
      sensitivity in humans with type 2 diabetes mellitus; however, the contributions
      of peripheral and hepatic tissues to these improvements are not known. OBJECTIVE:
      Our objective was to determine the effect of 7-d aerobic exercise training on
      peripheral and hepatic insulin sensitivity during isoglycemic/hyperinsulinemic
      clamp conditions. DESIGN: Subjects were randomly assigned to one of two groups.
      The energy balance group consumed an isocaloric diet consisting of 50%
      carbohydrate, 30% fat, and 20% protein for 15 d. The energy balance plus exercise
      group consumed a similar diet over the 15 d and performed 50-min of treadmill
      walking at 70% of maximum oxygen consumption maximum during the second 7 d of the
      15-d study period. Each subject underwent an initial isoglycemic/hyperinsulinemic
      clamp after 1-wk dietary control and a second clamp after completing the study.
      SETTING: The study was performed at Ohio State University's General Clinical
      Research Center. PARTICIPANTS: There were 18 obese, mildly diabetic humans
      included in the study. INTERVENTION: Aerobic exercise training was performed for
      7 d. MAIN OUTCOME MEASURES: Whole-body, peripheral, and hepatic insulin
      sensitivity were measured. RESULTS: Exercise training did not have an impact on
      peripheral glucose uptake or endogenous glucose production during the basal state
      or low-dose insulin. Likewise, it did not alter endogenous glucose production
      during high-dose insulin. However, 1-wk of exercise training increased both whole
      body (P<0.05) and peripheral insulin sensitivity (P<0.0001) during high-dose
      insulin. CONCLUSION: Improvements to whole body insulin sensitivity after short
      term aerobic exercise training are due to gains in peripheral, not heptic insulin
      sensitivity.

PMID- 18073313
TI  - Gonadal status and body mass index jointly determine growth hormone (GH)
      releasing hormone/GH-releasing peptide synergy in healthy men.
AB  - CONTEXT: Sex steroid hormones potentiate whereas increased body mass index (BMI)
      represses GH secretion. Whether sex steroids modify the negative effect of BMI on
      secretagogue-induced GH secretion in men is not known. The issue is important in
      designing GH-stimulation regimens that are relatively insensitive to both gonadal
      status and adiposity. OBJECTIVE: Our objective was to compare the relationships
      between BMI and peptide-stimulated GH secretion in men with normal and reduced
      testosterone and estradiol availability. SETTING: The study was performed at an
      academic medical center. SUBJECTS: Healthy young men were included in the study.
      INTERVENTIONS: Randomized separate-day iv infusion of saline and/or maximally
      effective doses of L-arginine/GHRH, L-arginine/GH-releasing peptide (GHRP)-2, and
      GHRH/GHRP-2 in eugonadal (n=12) and experimentally hypogonadal (n=10) men was
      performed. OUTCOMES: Regression of paired secretagogue-induced GH responses on
      BMI was determined. RESULTS: In eugonadal men, peak GH concentrations correlated
      negatively with BMI. In particular, BMI accounted for only 38% of the response
      variability after L-arginine/GHRH (P=0.0165), but 62% after GHRH/GHRP-2
      (P=0.0012) and 65% after L-arginine/GHRP-2 (P=0.00075). In contrast, in
      hypogonadal men, GH responses were uncorrelated with BMI. The negative effects of
      BMI on peak GH responses in eugonadal and hypogonadal states differed most
      markedly after stimulation with GHRH/GHRP-2 (P=0.0019). This contrast was
      corroborated using integrated GH responses (P=0.0007). CONCLUSIONS: Short-term
      experimental gonadal sex hormone depletion attenuates dual secretagogue
      stimulated GH secretion in lean young men. The inhibitory effect of relative
      adiposity on GH secretion appears to predominate over that of acute sex steroid
      withdrawal.

PMID- 18073314
TI  - Type 2 deiodinase polymorphism (threonine 92 alanine) predicts L-thyroxine dose
      to achieve target thyrotropin levels in thyroidectomized patients.
AB  - CONTEXT: Type 2 deiodinase (D2) converts T4 in T3 in several human tissues,
      including hypothalamus and pituitary, and, therefore, plays a pivotal role in the
      negative feedback regulation of TSH secretion. A common variant of the gene,
      threonine (Thr) 92 alanine (Ala), has been identified and associated with
      decreased D2 enzymatic activity. OBJECTIVE: Our objective was to investigate
      whether this polymorphism predicts the T4 dosage needed to obtain target TSH
      levels in thyroidectomized patients. SETTING: Ambulatory patients were included
      in the study. PATIENTS: A total of 191 consecutive thyroid cancer patients,
      previously treated by near total thyroidectomy and radioiodine ablation, were
      studied. They were on stable T4 dose treatment aimed at obtaining either
      suppressed (supp) (n=117, <0.1 mU/liter) or near-supp (n=74, >or=0.1<0.5
      mU/liter) serum TSH levels. MAIN OUTCOME MEASURES: DNA genotyping for D2 Thr92Ala
      variant and evaluation of T4 dose (microg/kg) needed to obtain target TSH levels
      were determined. RESULTS: Ala/Ala homozygous patients needed a higher T4 dose as
      compared with patients carrying the Thr92 variant (X/Thr patients) according to a
      recessive genetic model (2.08+/-0.43 vs. 1.90+/-0.35 microg/kg; P<0.05). This
      difference was observable in the near-supp group (P=0.002), but not in the supp
      group (P=0.4). CONCLUSIONS: D2 Thr92Ala polymorphism seems to predict the need
      for higher T4 intake in thyroidectomized patients. If this finding is confirmed
      in additional studies, it may predict the T4 requirement to suppress TSH on the
      basis of the individual genetic background.

PMID- 18073315
TI  - Gene expression of purified beta-cell tissue obtained from human pancreas with
      laser capture microdissection.
AB  - CONTEXT: Human beta-cell gene profiling is a powerful tool for understanding beta
      cell biology in normal and pathological conditions. Assessment is complicated
      when isolated islets are studied because of contamination by non-beta-cells and
      the trauma of the isolation procedure. OBJECTIVE: The objective was to use laser
      capture microdissection (LCM) of human beta-cells from pancreases of cadaver
      donors and compare their gene expression with that of handpicked isolated islets.
      DESIGN: Endogenous autofluorescence of beta-cells facilitated procurement of
      purified beta-cell tissue from frozen pancreatic sections with LCM. Gene
      expression profiles of three microdissected beta-cell samples and three isolated
      islet preparations were obtained. The array data were normalized using DNA-Chip
      Analyzer software (Harvard School of Public Health, Boston, MA), and the lower
      confidence bound evaluated differentially expressed genes. Real-time PCR was
      performed on selected acinar genes and on the duct cell markers, carbonic
      anhydrase II and keratin 19. RESULTS: Endogenous autofluorescence facilitates the
      microdissection of beta-cell rich tissue in human pancreas. When compared with
      array profiles of purified beta-cell tissue, with lower confidence bound set at
      1.2, there were 4560 genes up-regulated and 1226 genes down-regulated in the
      isolated islets. Among the genes up-regulated in isolated islets were pancreatic
      acinar and duct genes, chemokine genes, and genes associated with hypoxia,
      apoptosis, and stress. Quantitative RT-PCR confirmed the differential expression
      of acinar gene transcripts and the duct marker carbonic anhydrase II in isolated
      islets. CONCLUSION: LCM makes it possible to obtain beta-cell enriched tissue
      from human pancreas sections without the trauma and ischemia of islet isolation.

PMID- 18073316
TI  - The relationship between alcohol consumption and cortisol secretion in an aging
      cohort.
AB  - CONTEXT: Evidence for an association between alcohol consumption and activity of
      the hypothalamic-pituitary-adrenal (HPA) axis is inconclusive. OBJECTIVE: Our
      objective was to assess the relationship between indices of alcohol consumption
      and salivary cortisol concentration. DESIGN: This was a cross-sectional study of
      alcohol consumption and cortisol secretion from phase 7 (2002-2004) of the
      Whitehall II study. SETTING: An occupational cohort originally recruited in 1985
      1987 was included in the study. PARTICIPANTS: A total of 2693 men and 977 women
      had information on cortisol levels and alcohol consumption. OUTCOME MEASURES:
      Saliva samples were taken on waking, waking+0.5, 2.5, 8, and 12 h, and bedtime
      for the assessment of cortisol. RESULTS: In men there was a positive association
      between cortisol and units of alcohol intake per week (3% increase in cortisol
      per unit of alcohol consumed; P=0.010). The slope of cortisol decline over the
      day in heavy drinkers was reduced (heavy drinkers beta=-0.155, moderate drinkers
      beta=-0.151), indicating reduced control of the HPA axis in heavy drinkers. In
      women the cortisol awakening response was greater in heavy drinkers 14.15
      nmol/liter (9.12-19.17) compared with moderate drinkers 8.69 nmol/liter (7.72
      9.67) (P=0.037). CONCLUSIONS: This study suggests that alcohol consumption is
      associated with activation of the HPA axis. These results are not due to alcohol
      consumption on the day, suggesting chronic changes of the HPA axis in heavy
      drinking groups.

PMID- 18073317
TI  - Testosterone exacerbates obstructive renal injury by stimulating TNF-alpha
      production and increasing proapoptotic and profibrotic signaling.
AB  - Upper urinary tract obstruction is a common cause of renal dysfunction in
      children and adults. While there is clinical evidence of an increased male
      incidence and mortality rate with acute renal failure, the effect of gender and
      testosterone on obstructive renal injury has not previously been evaluated. We
      hypothesized that testosterone exacerbates proinflammatory TNF-alpha production
      and proapoptotic and profibrotic signaling during renal obstruction, resulting in
      increased apoptotic cell death and tubulointerstitial fibrosis. To study this,
      male, female, castrated male, and testosterone-treated oophorectomized female
      rats were subjected to sham operation or 3 days of unilateral ureteral
      obstruction (UUO). Renal cortical tissue was then analyzed for TNF-alpha
      production; proapoptotic caspase-8, -9, and -3 activity; apoptotic cell death;
      profibrotic transforming growth factor-beta1 production; and alpha-smooth muscle
      actin expression. In a separate arm, glomerular filtration rate (inulin
      clearance) was measured in rats pre- and post-UUO. Male and testosterone-treated
      oophorectomized female rats demonstrated a significant increase in TNF-alpha
      production, caspase activity, apoptotic cell death, tubulointerstitial fibrosis,
      and renal dysfunction during UUO compared with castrated males and normal female
      rats subjected to the same time course of obstruction. These results demonstrate
      that endogenous testosterone production in normal male rats and testosterone
      exogenously administered to oophorectomized females significantly increases TNF
      production and proapoptotic and profibrotic signaling during renal obstruction,
      resulting in increased apoptotic cell death, tubulointerstitial fibrosis, and
      renal dysfunction.

PMID- 18073318
TI  - Sexual dimorphism in the acute effects of secondhand smoke on thyroid hormone
      secretion, inflammatory markers and vascular function.
AB  - Experimental evidence for the physiological effects of secondhand smoke (SHS) is
      limited, although it affects millions of people globally and its prevalence is
      increasing, despite currently adopted antismoking measures. Also, scarce evidence
      suggests that the effects of SHS may be more pronounced in men. We conducted a
      randomized single-blind crossover study to investigate the sex-specific SHS
      effects in a controlled simulated bar/restaurant environment on gonadal and
      thyroid hormones, inflammatory cytokines, and vascular function. Twenty-eight
      (women = 14) nonsmoking adults underwent a 1-h exposure to moderate SHS and a 1-h
      control trial. Serum and urine cotinine, gonadal and thyroid hormones,
      inflammatory cytokines, heart rate, and arterial blood pressure were assessed
      before exposure and immediately after in both trials. Results showed that
      testosterone (P = 0.019) and progesterone (P < 0.001) in men and 17beta-estradiol
      (P = 0.001) and progesterone (P < 0.001) in women were significantly decreased
      after SHS. In men, SHS was accompanied by increased free thyroxine (P < 0.001),
      triiodothyronine (P = 0.020), and decreased the triiodothyronine-to-free
      thyroxine ratio (P = 0.033). In women, significant SHS-induced change was
      observed only in free thyroxine (P = 0.010), with considerable sex variation in
      free thyroxine and triiodothyronine and a decrease in luteinizing hormone (P =
      0.026) and follicle-stimulating hormone (P < 0.001). After SHS, IL-1beta (P =
      0.001) and systolic blood pressure (P = 0.040) were increased in men but not
      women. We concluded that a 1-h SHS exposure at bar/restaurant levels is
      accompanied by decrements in gonadal hormones in both sexes and marked increases
      in thyroid hormone secretion, IL-1beta production, and systolic blood pressure in
      men.

PMID- 18073319
TI  - PGC-1alpha is not mandatory for exercise- and training-induced adaptive gene
      responses in mouse skeletal muscle.
AB  - The aim of the present study was to test the hypothesis that peroxisome
      proliferator activated receptor-gamma coactivator (PGC) 1alpha is required for
      exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC
      1alpha knockout (KO) and littermate wild-type (WT) mice performed a single
      treadmill-running exercise bout. Soleus and white gastrocnemius (WG) were
      obtained immediately, 2 h, or 6 h after exercise. Another group of PGC-1alpha KO
      and WT mice performed 5-wk exercise training. Soleus, WG, and quadriceps were
      obtained approximately 37 h after the last training session. Resting muscles of
      the PGC-1alpha KO mice had lower ( approximately 20%) cytochrome c (cyt c),
      cytochrome oxidase (COX) I, and aminolevulinate synthase (ALAS) 1 mRNA and
      protein levels than WT, but similar levels of AMP-activated protein kinase (AMPK)
      alpha1, AMPKalpha2, and hexokinase (HK) II compared with WT mice. A single
      exercise bout increased phosphorylation of AMPK and acetyl-CoA carboxylase-beta
      and the level of HKII mRNA similarly in WG of KO and WT. In contrast, cyt c mRNA
      in soleus was upregulated in WT muscles only. Exercise training increased cyt c,
      COXI, ALAS1, and HKII mRNA and protein levels equally in WT and KO animals, but
      cyt c, COXI, and ALAS1 expression remained approximately 20% lower in KO animals.
      In conclusion, lack of PGC-1alpha reduced resting expression of cyt c, COXI, and
      ALAS1 and exercise-induced cyt c mRNA expression. However, PGC-1alpha is not
      mandatory for training-induced increases in ALAS1, COXI, and cyt c expression,
      showing that factors other than PGC-1alpha can exert these adaptations.

PMID- 18073320
TI  - Accretion of visceral fat and hepatic insulin resistance in pregnant rats.
AB  - Insulin resistance (IR) is a hallmark of pregnancy. Because increased visceral
      fat (VF) is associated with IR in nonpregnant states, we reasoned that fat
      accretion might be important in the development of IR during pregnancy. To
      determine whether VF depots increase in pregnancy and whether VF contributes to
      IR, we studied three groups of 6-mo-old female Sprague-Dawley rats: 1)
      nonpregnant sham-operated rats (Nonpreg; n = 6), 2) pregnant sham-operated rats
      (Preg; n = 6), and 3) pregnant rats in which VF was surgically removed 1 mo
      before mating (PVF-; n = 6). VF doubled by day 19 of pregnancy (Nonpreg 5.1 +/-
      0.3, Preg 10.0 +/- 1.0 g, P < 0.01), and PVF- had similar amounts of VF compared
      with Nonpreg (PVF- 4.6 +/- 0.8 g). Insulin sensitivity was measured by
      hyperinsulinemic-euglycemic clamp in late gestation in chronically catheterized
      unstressed rats. Glucose IR (mg.kg(-1).min(-1)) was highest in Nonpreg (19.4 +/-
      2.0), lowest in Preg (11.1 +/- 1.4), and intermediate in PVF- (14.7 +/- 0.6; P <
      0.001 between all groups). During the clamp, Nonpreg had greater hepatic insulin
      sensitivity than Preg [hepatic glucose production (HGP): Nonpreg 4.5 +/- 1.3,
      Preg 9.3 +/- 0.5 mg.kg(-1).min(-1); P < 0.001]. With decreased VF, hepatic
      insulin sensitivity was similar to nonpregnant levels in PVF- (HGP 4.9 +/- 0.8
      mg.kg(-1).min(-1)). Both pregnant groups had lower peripheral glucose uptake
      compared with Nonpreg. In parallel with hepatic insulin sensitivity, hepatic
      triglyceride content was increased in pregnancy (Nonpreg 1.9 +/- 0.4 vs. Preg 3.2
      +/- 0.3 mg/g) and decreased with removal of VF (PVF- 1.3 +/- 0.4 mg/g; P < 0.05).
      Accretion of visceral fat is an important component in the development of hepatic
      IR in pregnancy, and accumulation of hepatic triglycerides is a mechanism by
      which visceral fat may modulate insulin action in pregnancy.

PMID- 18073321
TI  - Angiotensin II-induced skeletal muscle insulin resistance mediated by NF-kappaB
      activation via NADPH oxidase.
AB  - Reduced insulin sensitivity is a key factor in the pathogenesis of type 2
      diabetes and hypertension. Skeletal muscle insulin resistance is particularly
      important for its major role in insulin-mediated glucose disposal. Angiotensin II
      (ANG II) is integral in regulating blood pressure and plays a role in the
      pathogenesis of hypertension. In addition, we have documented that ANG II-induced
      skeletal muscle insulin resistance is associated with generation of reactive
      oxygen species (ROS). However, the linkage between ROS and insulin resistance in
      skeletal muscle remains unclear. To explore potential mechanisms, we employed the
      transgenic TG(mRen2)27 (Ren-2) hypertensive rat, which harbors the mouse renin
      transgene and exhibits elevated tissue ANG II levels, and skeletal muscle cell
      culture. Compared with Sprague-Dawley normotensive control rats, Ren-2 skeletal
      muscle exhibited significantly increased oxidative stress, NF-kappaB activation,
      and TNF-alpha expression, which were attenuated by in vivo treatment with an
      angiotensin type 1 receptor blocker (valsartan) or SOD/catalase mimetic (tempol).
      Moreover, ANG II treatment of L6 myotubes induced NF-kappaB activation and TNF
      alpha production and decreased insulin-stimulated Akt activation and GLUT-4
      glucose transporter translocation to plasma membranes. These effects were
      markedly diminished by treatment of myotubes with valsartan, the antioxidant N
      acetylcysteine, NADPH oxidase-inhibiting peptide (gp91 ds-tat), or NF-kappaB
      inhibitor (MG-132). Similarly, NF-kappaB p65 small interfering RNA reduced NF
      kappaB p65 subunit expression and nuclear translocation and TNF-alpha production
      but improved insulin-stimulated phosphorylation (Ser(473)) of Akt and
      translocation of GLUT-4. These findings suggest that NF-kappaB plays an important
      role in ANG II/ROS-induced skeletal muscle insulin resistance.

PMID- 18073322
TI  - Maternal supply of omega-3 polyunsaturated fatty acids alter mechanisms involved
      in oocyte and early embryo development in the mouse.
AB  - Despite the well-known benefits of omega-3 (n-3) polyunsaturated fatty acid
      (PUFA) supplementation on human health, relatively little is known about the
      effect of n-3 PUFA intake on fertility. More specifically, the aim of this study
      was to determine how oocyte and preimplantation embryo development might be
      influenced by n-3 PUFA supply and to understand the possible mechanisms
      underlying these effects. Adult female mice were fed a control diet or a diet
      relatively high in the long-chain n-3 PUFAs for 4 wk, and ovulated oocytes or
      zygotes were collected after gonadotropin stimulation. Oocytes were examined for
      mitochondrial parameters (active mitochondrial distribution, mitochondrial
      calcium and membrane potential) and oxidative stress, and embryo developmental
      ability was assessed at the blastocyst stage following 1) in vitro fertilization
      (IVF) or 2) culture of in vivo-derived zygotes. This study demonstrated that
      exposure of the oocyte during maturation in the ovary to an environment high in n
      3 PUFA resulted in altered mitochondrial distribution and calcium levels and
      increased production of reactive oxygen species. Despite normal fertilization and
      development in vitro following IVF, the exposure of oocytes to an environment
      high in n-3 PUFA during in vivo fertilization adversely affected the
      morphological appearance of the embryo and decreased developmental ability to the
      blastocyst stage. This study suggests that high maternal dietary n-3 PUFA
      exposure periconception reduces normal embryo development in the mouse and is
      associated with perturbed mitochondrial metabolism, raising questions regarding
      supplementation with n-3 PUFAs during this period of time.

PMID- 18073323
TI  - A central role for hepatocyte growth factor in adipose tissue angiogenesis.
AB  - Hepatocyte growth factor (HGF) is a potent mitogenic and angiogenic factor
      produced in human adipose tissue. In this study, we use 3T3-F442A preadipocytes
      to study the contribution of HGF to angiogenesis in an in vivo fat pad
      development model. As observed for human adipocytes, HGF is synthesized and
      secreted by 3T3-F442A preadipocytes and mature adipocytes. HGF knockdown with
      small-interfering RNA reduced HGF mRNA expression 82.3 +/- 4.2% and protein
      secretion 82.9 +/- 1.4% from 3T3-F442A preadipocytes. Silencing of HGF resulted
      in a 70.5 +/- 19.0% reduction in endothelial progenitor cell migration to 3T3
      F442A-conditioned medium in vitro. 3T3-F442A preadipocytes injected under the
      skin of mice form a fat pad containing mature, lipid-filled adipocytes and a
      functional vasculature. At 72 h postinjection, expression of the endothelial cell
      genes TIE-1 and platelet endothelial cell adhesion molecule (PECAM)-1 was
      decreased 94.4 +/- 2.2 and 91.5 +/- 2.5%, respectively, in 3T3-F442A fat pads
      with HGF silencing. Knockdown of HGF had no effect on differentiation of 3T3
      F442A preadipocytes to mature adipocytes in vitro or in vivo. In developing fat
      pads under the skin of HGF overexpressing transgenic mice, TIE-1 and PECAM-1 mRNA
      was increased 16.5- and 21.4-fold, respectively, at 72 h postinjection. The
      increase in gene expression correlated with immunohistochemical evidence of
      endothelial cell migration in the developing fat pad. These data suggest that HGF
      has a central role in regulating angiogenesis in adipose tissue.

PMID- 18073325
TI  - An accelerometry-based comparison of 2 robotic assistive devices for treadmill
      training of gait.
AB  - OBJECTIVE: Two commercial robotic devices, the Gait Trainer (GT) and the Lokomat
      (LOKO), assist task-oriented practice of walking. The gait patterns induced by
      these motor-driven devices have not been characterized and compared. METHODS: A
      healthy participant chose the most comfortable gait pattern on each device and
      for treadmill (TM) walking at 1, 2 (maximum for the GT), and 3 km/h and over
      ground at similar speeds. A system of accelerometers on the thighs and feet
      allowed the calculation of spatiotemporal features and accelerations during the
      gait cycle. RESULTS: At the 1 and 2 km/h speed settings, single-limb stance times
      were prolonged on the devices compared with overground walking. Differences on
      the LOKO were decreased by adjusting the hip and knee angles and step length. At
      the 3 km/h setting, the LOKO approximated the participant's overground
      parameters. Irregular accelerations and decelerations from toe-off to heel
      contact were induced by the devices, especially at slower speeds. CONCLUSIONS:
      The LOKO and GT impose mechanical constraints that may alter leg accelerations
      decelerations during stance and swing phases, as well as stance duration,
      especially at their slower speed settings, that are not found during TM and
      overground walking. The potential impact of these perturbations on training to
      improve gait needs further study.

PMID- 18073327
TI  - Tilting at windmills: a response to a recent critique of terminal restriction
      fragment length polymorphism data.

PMID- 18073324
TI  - Motor skill training, but not voluntary exercise, improves skilled reaching after
      unilateral ischemic lesions of the sensorimotor cortex in rats.
AB  - BACKGROUND AND PURPOSE: Exercise and rehabilitative training each have been
      implicated in the promotion of restorative neural plasticity after cerebral
      injury. Because motor skill training induces synaptic plasticity and exercise
      increases plasticity-related proteins, we asked if exercise could improve the
      efficacy of training on a skilled motor task after focal cortical lesions.
      METHODS: Female young and middle-aged rats were trained on the single-pellet
      retrieval task and received unilateral ischemic sensorimotor cortex lesions
      contralateral to the trained limb. Rats then received both, either, or neither
      voluntary running and/or rehabilitative training for 5 weeks beginning 5 days
      postlesion. Motor skill training consisted of daily practice of the impaired
      forelimb in a tray-reaching task. Exercised rats had free access to running
      wheels for 6 h/day. Reaching function was periodically probed using the single
      pellet retrieval task. RESULTS: In young adults, motor skill training
      significantly enhanced skilled reaching recovery compared to controls. However,
      exercise did not significantly enhance performance when administered alone or in
      combination with skill training. There was also no major benefit of exercise in
      older rats. Additionally, there were no effects of exercise in a measure of
      coordinated forelimb placement (the foot-fault test) or in immunocytochemical
      measures of several plasticity-related proteins in the motor cortex. CONCLUSIONS:
      In young and middle-aged animals, exercise did not improve motor skill training
      efficacy following ischemic lesions. Practicing motor skills more effectively
      improved recovery of these skills than did exercise. It remains possible that an
      alternative manner of administering exercise would be more effective.

PMID- 18073328
TI  - Beliefs about medicines and adherence among Swedish migraineurs.
AB  - BACKGROUND: The problem of low adherence to drug therapy is as prevalent in
      migraine as in any other disorder, with important consequences for the patient,
      such as impaired quality of life and absence from work. Beliefs about medicines
      have been identified as one of the most significant factors for adherence.
      OBJECTIVE: To analyze whether beliefs about medicines and medication-related
      factors are associated with adherence to prophylactic drug therapy among
      migraineurs at a Swedish tertiary care clinic. METHODS: A questionnaire was
      distributed to migraineurs visiting a tertiary care clinic in Sweden. All
      participants had recently been prescribed prophylactic medicine. The
      questionnaire was comprised of background questions, questions about disease
      characteristics, perceived effects, and adverse effects of migraine medications
      used, the Beliefs about Medicines questionnaire, and the Medication Adherence
      Report Scale. Medication-related variables, collected from patients' records with
      consent, were also included. Logistic regression analysis was performed to
      analyze the association between beliefs about medicines, medication-related
      variables, and adherence to prophylactic drugs. RESULTS: Of the 174 participants
      in the study, 64% were considered to be adherent to their prescribed prophylactic
      medicine. Users of beta-blockers were significantly more adherent compared with
      patients using other drugs (eg, tricyclic antidepressants [TCAs] or
      antiepileptics); the reverse was true for patients taking TCAs. Respondents with
      the lowest level of education (<or=9 y) expressed less concern about drugs and
      had a higher necessity-concerns differential compared with respondents with a
      higher educational level. In the final regression model, no variable was
      significantly associated with adherence. CONCLUSIONS: About one-third of the
      migraineurs did not adhere to their prophylactic drugs. Beliefs about medicines
      and medication-related factors could not predict nonadherence. We recommend
      further research on medication-related variables in relation to adherence among
      migraineurs.

PMID- 18073329
TI  - Simultaneous erythema nodosum and erythema multiforme after local lidocaine
      injection.
AB  - OBJECTIVE: To report a case of simultaneous erythema nodosum and erythema
      multiforme after local lidocaine injection. CASE SUMMARY: A 33-year-old female
      experienced coexisting erythema nodosum and erythema multiforme after lidocaine
      spray was used for upper gastrointestinal endoscopy. The reaction was exacerbated
      after localized injection of 2% lidocaine for a skin biopsy. An objective
      causality assessment revealed that an adverse drug reaction was highly probable.
      DISCUSSION: Lidocaine is the most frequently used local anesthetic agent. The
      coexistence of erythema nodosum and erythema multiforme has been reported in
      lepromatous leprosy, Yersinia enterocolitica and Yersinia pseudotuberculosis
      gastrointestinal infection (both with diarrhea), histoplasmosis, hepatitis C, and
      milkers nodule, but not with lidocaine. CONCLUSIONS: If clinicians observe
      similar lesions after lidocaine exposure, they should suspect an adverse drug
      reaction and exercise caution in the administration of amide anesthetics to
      patients with a documented history of adverse reaction to lidocaine.

PMID- 18073330
TI  - NF-kappaB-dependent expression of the antiapoptotic factor c-FLIP is regulated by
      calpain 3, the protein involved in limb-girdle muscular dystrophy type 2A.
AB  - Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder
      caused by mutations in the cysteine protease calpain 3 (CAPN3) that leads to
      selective muscle wasting. We previously showed that CAPN3 deficiency is
      associated with a profound perturbation of the NF-kappaB/IkappaB alpha survival
      pathway. In this study, the consequences of altered NF-kappaB/IkappaB alpha
      pathway were investigated using biological materials from LGMD2A patients. We
      first show that the antiapoptotic factor cellular-FLICE inhibitory protein (c
      FLIP), which is dependent on the NF-kappaB pathway in normal muscle cells, is
      down-regulated in LGMD2A biopsies. In muscle cells isolated from LGMD2A patients,
      NF-kappaB is readily activated on cytokine induction as shown by an increase in
      its DNA binding activity. However, we observed discrepant transcriptional
      responses depending on the NF-kappaB target genes. IkappaB alpha is expressed
      following NF-kappaB activation independent of the CAPN3 status, whereas
      expression of c-FLIP is obtained only when CAPN3 is present. These data lead us
      to postulate that CAPN3 intervenes in the regulation of the expression of NF
      kappaB-dependent survival genes to prevent apoptosis in skeletal muscle.
      Deregulations in the NF-kappaB pathway could be part of the mechanism responsible
      for the muscle wasting resulting from CAPN3 deficiency.

PMID- 18073331
TI  - Evolutionary determinants of divergent calcium selectivity of TRPM channels.
AB  - The mammalian TRPM gene family can be subdivided into distinct categories of
      cation channels that are either highly permeable for Ca(2+) (TRPM3/6/7),
      nonselective (TRPM2/8), or even Ca(2+) impermeable (TRPM4/5). TRPM6/7 are fused
      to alpha-kinase domains, whereas TRPM2 is linked to an ADP-ribose
      phosphohydrolase (Nudix domain). At a molecular level, the evolutionary steps
      that gave rise to the structural and functional TRPM channel diversity remain
      elusive. Here, we provide phylogenetic evidence that Nudix-linked channels
      represent an ancestral type of TRPMs that is present in various phyla, ranging
      from protists to humans. Surprisingly, the pore-forming segments of invertebrate
      TRPM2-like proteins display high sequence similarity to those of Ca(2+)-selective
      TRPMs, while human TRPM2 is characterized by a loss of several conserved
      residues. Using the patch-clamp technique, Ca(2+) imaging, and site-directed
      mutagenesis, we demonstrate that restoration of only two "ancient" pore residues
      in human TRPM2 (Q981E/P983Y) significantly increased (approximately 4-fold) its
      permeability for Ca(2+). Conversely, introduction of a "modern" sequence motif
      into mouse TRPM7 (E1047Q/Y1049P) resulted in the loss of Ca(2+) permeation and a
      linear TRPM2-like current-voltage relationship. Overall, our findings provide an
      integrative view on the evolution of the domain architecture and the structural
      basis of the distinct ion permeation profiles of TRPM channels.

PMID- 18073332
TI  - Laminin deposition is dispensable for vasculogenesis but regulates blood vessel
      diameter independent of flow.
AB  - Basement membranes (BMs) consisting of laminins, collagens, and heparan sulfate
      proteoglycans (HSPGs) are vital for proper endothelial cell function, but many
      aspects of their role in vascular development remain unknown. Here, we
      demonstrate that vascular structures within differentiating embryoid bodies are
      wrapped in a BM composed of alpha4- and alpha5-chain laminins, fibronectin,
      collagen IV, and HSPGs. In sprouting angiogenesis, laminins were produced by
      stalk cells, as well as the leading tip cell, and deposited along the sprout
      length, including tip cell filopodia. In embryonic stem cells deficient in
      laminins, due to lamc1 (laminin gamma1) deletion, vascular development and
      organization were largely unaffected. However, the frequency of vessels with wide
      lumens was increased 4-fold. Laminin-deficient vessels were moreover
      characterized by increased fibronectin levels and enhanced endothelial cell
      proliferation. We conclude that laminins are dispensable for vascular development
      but that they regulate lumen formation in the absence of flow and vascular tone.

PMID- 18073333
TI  - Cholecystokinin-A receptors regulate photic input pathways to the circadian
      clock.
AB  - Daily behaviors are strongly dominated by internally generated circadian rhythms,
      but the underlying mechanisms remain unclear. In mammals, photoentrainment of
      behaviors to light-dark cycles involves signaling from both intrinsically
      photosensitive retinal ganglion cells and classic photoreceptor pathways to the
      suprachiasmatic nucleus (SCN). How classic photoreceptor pathways work with the
      photosensitive ganglion cells, however, is not fully understood. Although
      cholecystokinin (CCK) peptide has been shown to be present in a variety of
      vertebrate retinas, its function at a systems level is also unknown. In the
      present study we examined a possible role of CCK-A receptors in photoentrainment
      using CCK-A receptor knockout mice. The lacZ reporter gene within a gene-knockout
      cassette revealed precise localization of CCK-A receptors in the circadian clock
      system. We demonstrated that CCK-A receptors were located predominately on
      glycinergic amacrine cells but were rarely found on SCN neurons. Moreover, Ca(2+)
      imaging analysis demonstrated that the CCK-A agonist, CCK-8 sulfate (CCK-8s),
      mobilized intracellular Ca(2+) in amacrine cells but not glutamate-receptive SCN
      neurons. Furthermore, light pulse-induced mPer1/mPer2 gene expression in SCN,
      behavioral phase shifts, and the pupillary reflex were significantly reduced in
      CCK-A receptor knockout mice. These data indicate a novel function of CCK-A
      receptors in the nonimage-forming photoreception presumably via amacrine cell
      mediated signal transduction pathways.

PMID- 18073334
TI  - Hypoxia-mediated Na-K-ATPase degradation requires von Hippel Lindau protein.
AB  - Hypoxia inhibits Na-K-ATPase activity and leads to its degradation in mammalian
      cells. Von Hippel Lindau protein (pVHL) and hypoxia inducible factor (HIF) are
      key mediators in cellular adaptation to hypoxia; thus, we set out to investigate
      whether pVHL and HIF participate in the hypoxia-mediated degradation of plasma
      membrane Na-K-ATPase. We found that in the presence of pVHL hypoxia decreased Na
      K-ATPase activity and promoted the degradation of plasma membrane Na-K-ATPase. In
      pVHL-deficient cells, hypoxia did not decrease the Na-K-ATPase activity and the
      degradation of plasma membrane Na-K-ATPase was prevented. pVHL-mediated
      degradation of Na-K-ATPase required the functional pVHL E3 ligase and Ubc5 since
      pVHL mutants and dominant-negative Ubc5 prevented Na-K-ATPase from degradation.
      The generation of reactive oxygen species was necessary for pVHL-mediated Na-K
      ATPase degradation during hypoxia. Desferrioxamine, which stabilizes HIF1/2alpha,
      did not affect the half-life of plasma membrane Na-K-ATPase. In addition,
      stabilizing HIF1/2alpha by infecting mammalian cells with adenoviruses containing
      the oxygen-dependent degradation domain of HIF1alpha did not affect the plasma
      membrane Na-K-ATPase degradation. In cells with suppression of pVHL by short
      hairpin RNA, the Na-K-ATPase was not degraded during hypoxia, whereas cells with
      knockdown of HIF1/2alpha retained the ability to degrade plasma membrane Na-K
      ATPase. These findings suggest that pVHL participates in the hypoxia-mediated
      degradation of plasma membrane Na-K-ATPase in a HIF-independent manner.

PMID- 18073335
TI  - Mechanism for ubiquitylation of the leukemia fusion proteins AML1-ETO and PML
      RARalpha.
AB  - The chromosomal translocation products AML1-ETO and PML-RARalpha contribute to
      the pathogenesis of leukemias. Here, we demonstrate that both AML1-ETO and PML
      RARalpha are degraded by the ubiquitin-proteasome system and that their turnover
      critically depends on the E2-conjugase UbcH8 and the E3-ligase SIAH-1. Contrary
      to its role in HDAC2 degradation, the E3-ligase RLIM does not target AML1-ETO and
      PML-RARalpha for ubiquitin-dependent elimination. RLIM rather is a substrate of
      SIAH-1, which indicates that these E3-ligases operate in a hierarchical order.
      Remarkably, proteasomal degradation of leukemia fusion proteins, in addition to
      the block of histone deacetylase (HDAC) enzymatic activity is a consequence of
      HDAC-inhibitor treatment. The former requires the induction of UbcH8 expression
      and each of these processes might be beneficial for leukemia treatment. Our
      observations shed light on the mechanism determining the interplay between E2
      conjugases, E3-ligases, and their substrates and suggest a strategy for utilizing
      the ubiquitylation machinery in a therapeutic setting.

PMID- 18073336
TI  - Introduction and overview of worksite studies.

PMID- 18073337
TI  - Worksite study promoting activity and changes in eating (PACE): design and
      baseline results.
AB  - OBJECTIVE: Based on previous worksite-wide intervention studies and an ecological
      framework, we created a behavioral intervention program to maintain or reduce
      weight through healthy eating and physical activity. The design and evaluation
      plan of the group-randomized trial and the recruitment of worksites are
      described. Preliminary results regarding the dietary and physical activity
      behaviors associated with BMI are discussed. RESEARCH METHODS AND PROCEDURES: The
      intervention used an ecological framework modified by qualitative methods that
      identified salient barriers and facilitators of behavioral change. Approximately
      30 transportation, manufacturing, utilities, personal, household, and
      miscellaneous service companies in the greater Seattle area are being recruited
      to the trial. The study population for the present analysis consists of 18
      worksites from the first two randomization waves. Dietary behavior was assessed,
      not by calories, but by behavioral measures related to BMI. Physical activity
      behaviors were surveyed. BMI is derived from reported height and weight at
      baseline. RESULTS: The intervention has been developed with a specified minimum
      suite of strategies within the defined framework. Response rates to the baseline
      survey among the 18 worksites are 81% on average. After adjusting for age,
      gender, race, and education, BMI was associated with frequency of intensity
      adjusted physical activity, sweat-inducing exercise, fast food meals, soft
      drinks, eating while doing another activity, and fruit and vegetable intake.
      DISCUSSION: Worksite-wide intervention strategies can be adapted to target
      obesity prevention. Employees are willing to participate in surveys at high
      rates. Several measures of physical activity and eating choices are associated
      with baseline BMI.

PMID- 18073338
TI  - Work, Weight, and Wellness: the 3W Program: a worksite obesity prevention and
      intervention trial.
AB  - OBJECTIVE: In this paper, we describe the aims, intervention, and design of the
      Work, Weight, and Wellness program, a group-randomized worksite obesity
      prevention and intervention trial being conducted at 31 hotels with 11,559
      employees on the island of Oahu in Hawaii. We report baseline prevalence of
      overweight and obesity, and the distribution of BMI (kilograms per meter squared)
      across sex, race, and job categories. We also describe factors that have
      influenced intervention adoption and employee participation. RESEARCH METHODS AND
      PROCEDURES: The study's primary outcome is change in BMI among hotel employees
      over a 2-year intervention period. The intervention includes environmental and
      group components that target diet, physical activity, and weight management.
      RESULTS: Men, Pacific Islanders, and individuals employed in managerial or
      facility maintenance roles had higher prevalence of obesity and higher mean BMI
      than women and individuals from other races or in other occupational categories.
      DISCUSSION: These results may be helpful in guiding choices about the adoption or
      design of future worksite and community interventions addressing at-risk
      ethnically diverse populations and are especially relevant to the hotel industry
      and similar industries.

PMID- 18073339
TI  - Keeping a Step Ahead: formative phase of a workplace intervention trial to
      prevent obesity.
AB  - OBJECTIVE: Ecological interventions hold promise for promoting overweight and
      obesity prevention in worksites. Given the paucity of evaluative research in the
      hospital worksite setting, considerable formative work is required for successful
      implementation and evaluation. This paper describes the formative phases of Step
      Ahead, a site-randomized controlled trial of a multilevel intervention that
      promotes physical activity and healthy eating in six hospitals in central
      Massachusetts. The purpose of the formative research phase was to increase the
      feasibility, effectiveness, and likelihood of sustainability of the intervention.
      RESEARCH METHODS AND PROCEDURES: The Step Ahead ecological intervention approach
      targets change at the organization, interpersonal work environment, and
      individual levels. The intervention was developed using fundamental steps of
      intervention mapping and important tenets of participatory research. Formative
      research methods were used to engage leadership support and assistance and to
      develop an intervention plan that is both theoretically and practically grounded.
      This report uses observational data, program minutes and reports, and process
      tracking data. RESULTS: Leadership involvement (key informant interviews and
      advisory boards), employee focus groups and advisory boards, and quantitative
      environmental assessments cultivated participation and support. Determining
      multiple foci of change and designing measurable objectives and generic
      assessment tools to document progress are complex challenges encountered in
      planning phases. DISCUSSION: Multilevel trials in diverse organizations require
      flexibility and balance of theory application and practice-based perspectives to
      affect impact and outcome objectives. Formative research is an essential
      component.

PMID- 18073341
TI  - Development of ACTION! Wellness Program for Elementary School Personnel.
AB  - OBJECTIVE: The prevalence of overweight and obesity has increased dramatically in
      the adult population over the past 2 decades. Almost two-thirds of the adult
      population works outside the home; thus, interventions implemented at the
      worksite are viable for obesity reduction. Elementary schools are worksites that
      have a number of resources that can encourage a healthy lifestyle. The purpose of
      this paper is to describe the formative research activities and how these were
      used to design the ACTION! Wellness Program for Elementary School Personnel.
      RESEARCH METHODS AND PROCEDURES: Formative data were collected using focus
      groups, a school survey, and an environmental audit. Focus groups were conducted
      in three elementary schools, whereas the school survey and environmental audit
      were collected in 24 elementary schools. The intervention was then tested as a
      pilot study in one school to determine feasibility and receptivity and refine its
      components. RESULTS: Participants in the focus groups indicated that most had
      experience with trying to lose weight, some had positive social support, and most
      had little free time at school; however, most were very receptive to having a
      weight control intervention program at their school. Eighteen (75%) of the
      schools had snack vending machines on the school site, and all had cold drink
      machines. All 24 schools had at least one indoor site that could be used for
      physical activity programs. All schools were in neighborhoods conducive for
      walking. DISCUSSION: ACTION! will take advantage of the school resources in
      implementing an environmental intervention to reduce overweight and obesity. This
      paper describes the progression of events that led to the final trial.

PMID- 18073340
TI  - Using formative research to develop environmental and ecological interventions to
      address overweight and obesity.
AB  - OBJECTIVE: This paper presents the formative research phase of a large multi-site
      intervention study conducted to inform the feasibility of introducing
      environmental and ecological interventions. RESEARCH METHODS AND PROCEDURES:
      Using mixed methods that included an environmental assessment, climate survey,
      leadership focus groups and interviews, and archival data, information was
      collected on employee health and job factors, the physical environment, social
      organizational environment, and current health programs. RESULTS: Results show
      that 83% of employees at the study sites were overweight or obese. Leadership was
      very supportive of health initiatives and felt integrating the strategies into
      organizational operations would increase their likelihood of success.
      Environmental assessment scores ranged from 47 to 19 on a 100-point scale. Health
      services personnel tended to view the organizational climate for health more
      positively than site leadership (mean of 3.6 vs. 3.0, respectively). DISCUSSION:
      Intervention strategies chosen included increasing healthy food choices in
      vending, cafeterias, and company meetings, providing a walking path, targeting
      messages, developing site goals, training leaders, and establishing leaders at
      the work group level.

PMID- 18073342
TI  - "Pizza is cheaper than salad": assessing workers' views for an environmental food
      intervention.
AB  - OBJECTIVE: "Images of a Healthy Worksite" aims to provide easy access to
      healthful foods and to reduce sedentarism at the worksite-to prevent weight gain.
      Formative research for the nutrition intervention component was aimed at gaining
      a broad understanding of the sociocultural role of food and eating among workers
      and worker perspectives on socially feasible and culturally acceptable
      environmental intervention strategies. RESEARCH METHODS AND PROCEDURES: Using an
      adapted PRECEDE health planning model, we conducted ecological, educational,
      environmental, and administrative assessments at the worksite. Through 15 in
      depth interviews, five focus groups, and community mapping at two sites with 79
      administrators, managers, workers, and food service personnel (51% men, 82%
      white), we assessed workers' perspectives on physical, sociocultural, economic,
      and policy environments. Data were coded for predisposing, enabling, and
      reinforcing factors related to intervention strategies in vending, cafeteria,
      catering, and informal food environments. After classification for reach,
      intensity, and sustainability, objectives and evaluation plans were developed for
      each highly ranked strategy. RESULTS: Key sociocultural factors affecting food
      and eating included: stress-related eating in a downsizing workplace, enthusiasm
      for employer-sponsored weight gain prevention efforts that respect personal
      privacy, and the consequences of organizational culture on worker access to the
      food and eating environment. Workers supported healthier cafeteria and catering
      options, bringing healthful foods closer, and labeling of healthful options.
      DISCUSSION: We provide a practical and systematic approach to formative research
      and assess the interrelatedness of the physical, policy, economic, and
      sociocultural factors that affect environmental worksite interventions to prevent
      weight gain among employees.

PMID- 18073343
TI  - The role of the coordinating center in the obesity prevention at the worksite
      consortium.
AB  - This paper describes the role of the Coordinating Center for a seven-project
      consortium funded through a common request for applications. The seven studies
      are focusing on prevention and treatment of obesity at worksites. These projects
      are being conducted at different types of work sites that have diverse employee
      populations. The Center's functions include identifying opportunities for
      collaboration, encouraging communication among the project investigators,
      facilitating the adoption of common measures, combining data from two or more
      projects to achieve greater statistical power, and pooling data on measures such
      as physical activity, work productivity, health care use, and return on
      investment. To these ends, the Coordinating Center helped to develop a committee
      structure within the consortium, established a communications and data
      transmission web site, and arranged conference calls, committee meetings, and
      paper writing groups. The development and implementation of these functions are
      described in this paper.

PMID- 18073344
TI  - miR-122 targeting with LNA/2'-O-methyl oligonucleotide mixmers, peptide nucleic
      acids (PNA), and PNA-peptide conjugates.
AB  - MicroRNAs are small noncoding RNAs that regulate many cellular processes in a
      post-transcriptional mode. MicroRNA knockdown by antisense oligonucleotides is a
      useful strategy to explore microRNA functionality and as potential therapeutics.
      MicroRNA-122 (miR-122) is a liver-specific microRNA, the main function of which
      has been linked with lipid metabolism and liver homeostasis. Here, we show that
      lipofection of an antisense oligonucleotide based on a Locked Nucleic Acids
      (LNA)/2'-O-methyl mixmer or electroporation of a Peptide Nucleic Acid (PNA)
      oligomer is effective at blocking miR-122 activity in human and rat liver cells.
      These oligonucleotide analogs, evaluated for the first time in microRNA
      inhibition, are more effective than standard 2'-O-methyl oligonucleotides in
      binding and inhibiting microRNA action. We also show that microRNA inhibition can
      be achieved without the need for transfection or electroporation of the human or
      rat cell lines, by conjugation of an antisense PNA to the cell-penetrating
      peptide R6-Penetratin, or merely by linkage to just four Lys residues,
      highlighting the potential of PNA for future therapeutic applications as well as
      for studying microRNA function.

PMID- 18073345
TI  - Diverse roles of hnRNP L in mammalian mRNA processing: a combined microarray and
      RNAi analysis.
AB  - Alternative mRNA splicing patterns are determined by the combinatorial control of
      regulator proteins and their target RNA sequences. We have recently characterized
      human hnRNP L as a global regulator of alternative splicing, binding to diverse
      C/A-rich elements. To systematically identify hnRNP L target genes on a genome
      wide level, we have combined splice-sensitive microarray analysis and an RNAi
      knockdown approach. As a result, we describe 11 target genes of hnRNP L that were
      validated by RT-PCR and that represent several new modes of hnRNP L-dependent
      splicing regulation, involving both activator and repressor functions: first,
      intron retention; second, inclusion or skipping of cassette-type exons; third,
      suppression of multiple exons; and fourth, alternative poly(A) site selection. In
      sum, this approach revealed a surprising diversity of splicing-regulatory
      processes as well as poly(A) site selection in which hnRNP L is involved.

PMID- 18073346
TI  - Autocrine formation of hepcidin induces iron retention in human monocytes.
AB  - Hepcidin, a master regulator of iron homeostasis, is produced in small amounts by
      inflammatory monocytes/macrophages. Chronic immune activation leads to iron
      retention within monocytes/macrophages and the development of anemia of chronic
      disease (ACD). We questioned whether monocyte-derived hepcidin exerts autocrine
      regulation toward cellular iron metabolism. Monocyte hepcidin mRNA expression was
      significantly induced within 3 hours after stimulation with LPS or IL-6, and
      hepcidin mRNA expression was significantly higher in monocytes of ACD patients
      than in controls. In ACD patients, monocyte hepcidin mRNA levels were
      significantly correlated to serum IL-6 concentrations, and increased monocyte
      hepcidin mRNA levels were associated with decreased expression of the iron
      exporter ferroportin and iron retention in these cells. Transient transfection
      experiments using a ferroportin/EmGFP fusion protein construct demonstrated that
      LPS inducible hepcidin expression in THP-1 monocytes resulted in internalization
      and degradation of ferroportin. Transfection of monocytes with siRNA directed
      against hepcidin almost fully reversed this lipopolysaccharide-mediated effect.
      Using ferroportin mutation constructs, we found that ferroportin is mainly
      targeted by hepcidin when expressed on the cell surface. Our results suggest that
      ferroportin expression in inflammatory monocytes is negatively affected by
      autocrine formation of hepcidin, thus contributing to iron sequestration within
      monocytes as found in ACD.

PMID- 18073347
TI  - PI5KI-dependent signals are critical regulators of the cytolytic secretory
      pathway.
AB  - Although membrane phospholipid phosphatidylinositol-4,5bisphosphate (PIP2) plays
      a key role as signaling intermediate and coordinator of actin dynamics and
      vesicle trafficking, it remains completely unknown its involvement in the
      activation of cytolytic machinery. By live confocal imaging of primary human
      natural killer (NK) cells expressing the chimeric protein GFP-PH, we observed,
      during effector-target cell interaction, the consumption of a preexisting PIP2
      pool, which is critically required for the activation of cytolytic machinery. We
      identified type I phosphatidylinositol-4-phosphate-5-kinase (PI5KI) alpha and
      gamma isoforms as the enzymes responsible for PIP2 synthesis in NK cells. By hRNA
      driven gene silencing, we observed that both enzymes are required for the proper
      activation of NK cytotoxicity and for inositol-1,4,5-trisphosphate (IP3)
      generation on receptor stimulation. In an attempt to elucidate the specific step
      controlled by PI5KIs, we found that lytic granule secretion but not polarization
      resulted in impaired PI5KIalpha- and PI5KIgamma-silenced cells. Our findings
      delineate a novel mechanism implicating PI5KIalpha and PI5KIgamma isoforms in the
      synthesis of PIP2 pools critically required for IP3-dependent Ca(2+) response and
      lytic granule release.

PMID- 18073348
TI  - Haploinsufficiency of CDKN1B contributes to leukemogenesis in T-cell
      prolymphocytic leukemia.
AB  - T-cell prolymphocytic leukemia (T-PLL) is consistently associated with
      inactivation of the ATM gene and chromosomal re-arrangements leading to an
      overexpression of MTCP1/TCL1 oncoproteins. These alterations are present at the
      earliest stage of malignant transformation, suggesting that additional events are
      required for overt malignancy. In this study, we pursued the investigation of the
      12p13 deletion, previously shown to occur in approximately half of T-PLLs. We
      refined the minimal region of deletion by single nucleotide and microsatellite
      polymorphism allelotyping. We defined a 216-kb region containing the CDKN1B gene
      that encodes the cyclin-dependent kinase inhibitory protein p27(KIP1). Sequencing
      this gene in 47 T-PLL patient samples revealed a nonsense mutation in one case
      without 12p13 deletion. The absence of biallelic inactivation of CDKN1B for most
      patients suggested a haploinsufficiency mechanism for tumor suppression, which
      was investigated in an animal model of the disease. In a Cdkn1b(+/-) background,
      MTCP1 transgenics had consistent and multiple emergences of preleukemic clones
      not observed in control cohorts. The second Cdkn1b allele was maintained and
      expressed in these preleukemic clones. Altogether, these data strongly implicate
      CDKN1B haploinsufficiency in the pathogenesis of T-PLL.

PMID- 18073349
TI  - Alternative mRNA is favored by the A3 haplotype of the EPCR gene PROCR and
      generates a novel soluble form of EPCR in plasma.
AB  - The endothelial cell protein C receptor also exists in soluble form in plasma
      (sEPCR), resulting from ADAM17 cleavage. Elevated sEPCR levels are observed in
      subjects carrying the A3 haplotype, which is characterized by a Ser219Gly
      substitution in the transmembrane domain, rendering the receptor more sensitive
      to cleavage. Because sEPCR production is not completely blocked by
      metalloprotease inhibition, we looked for another mechanism. Comparing mRNA
      expression patterns and levels in A3 and non-A3 cells from 32 human umbilical
      cord veins, we detected a truncated mRNA in addition to the full-length mRNA.
      This truncated mRNA was 16 times more abundant in A3 human umbilical vein
      endothelial cells than in non-A3 human umbilical vein endothelial cells and
      encoded a protein lacking the transmembrane domain. We stably expressed a
      recombinant form of this protein (rEPCRisoform) and a protein mimicking the
      plasma sEPCR (rEPCRsol). Functional studies of the purified recombinant proteins
      revealed that the rEPCRisoform bound to recombinant protein C with similar
      affinity than rEPCRsol and that it also inhibited the anticoagulant activity of
      APC. Trace amounts of the EPCR isoform were found in the plasma of A3 subjects.
      These results suggest that the sEPCRisoform could contribute to the regulatory
      effect of sEPCR in plasma.

PMID- 18073350
TI  - Complete molecular response of e6a2 BCR-ABL-positive acute myeloid leukemia to
      imatinib then dasatinib.
AB  - De novo presentation of acute myeloid leukemia (AML) expressing the Philadelphia
      (Ph) chromosomal abnormality is rare and is associated with a dismal prognosis.
      To date, reported cases of Ph(+) AML have expressed either the e13a2 or e14a2 BCR
      ABL fusion transcripts. We report a unique case of de novo AML expressing the
      e6a2 fusion transcript and describe disease sensitivity to both imatinib before
      allogeneic stem-cell transplantation and dasatinib for AML relapse after
      allogeneic stem-cell transplantation. Furthermore, we report that sustained
      molecular remission has been achieved despite withdrawal of tyrosine kinase
      inhibitor (TKI) therapy.

PMID- 18073351
TI  - The cover. The Musicians.

PMID- 18073352
TI  - Education key to treating airway disease: focus on inhaler users, rescue workers,
      athletes.

PMID- 18073353
TI  - Aiding emergency research aim of report on exceptions to informed consent.

PMID- 18073354
TI  - Reports help identify and manage autism.

PMID- 18073355
TI  - Use of amiodarone.

PMID- 18073356
TI  - Use of amiodarone.

PMID- 18073357
TI  - Clinical magnetic resonance imaging of ancient dry human mummies without
      rehydration.

PMID- 18073358
TI  - Geriatric care management for low-income seniors: a randomized controlled trial.
AB  - CONTEXT: Low-income seniors frequently have multiple chronic medical conditions
      for which they often fail to receive the recommended standard of care.
      OBJECTIVES: To test the effectiveness of a geriatric care management model on
      improving the quality of care for low-income seniors in primary care. DESIGN,
      SETTING, AND PATIENTS: Controlled clinical trial of 951 adults 65 years or older
      with an annual income less than 200% of the federal poverty level, whose primary
      care physicians were randomized from January 2002 through August 2004 to
      participate in the intervention (474 patients) or usual care (477 patients) in
      community-based health centers. INTERVENTION: Patients received 2 years of home
      based care management by a nurse practitioner and social worker who collaborated
      with the primary care physician and a geriatrics interdisciplinary team and were
      guided by 12 care protocols for common geriatric conditions. MAIN OUTCOME
      MEASURES: The Medical Outcomes 36-Item Short-Form (SF-36) scales and summary
      measures; instrumental and basic activities of daily living (ADLs); and emergency
      department (ED) visits not resulting in hospitalization and hospitalizations.
      RESULTS: Intention-to-treat analysis revealed significant improvements for
      intervention patients compared with usual care at 24 months in 4 of 8 SF-36
      scales: general health (0.2 vs -2.3, P = .045), vitality (2.6 vs -2.6, P < .001),
      social functioning (3.0 vs -2.3, P = .008), and mental health (3.6 vs -0.3, P =
      .001); and in the Mental Component Summary (2.1 vs -0.3, P < .001). No group
      differences were found for ADLs or death. The cumulative 2-year ED visit rate per
      1000 was lower in the intervention group (1445 [n = 474] vs 1748 [n = 477], P =
      .03) but hospital admission rates per 1000 were not significantly different
      between groups (700 [n = 474] vs 740 [n = 477], P = .66). In a predefined group
      at high risk of hospitalization (comprising 112 intervention and 114 usual-care
      patients), ED visit and hospital admission rates were lower for intervention
      patients in the second year (848 [n = 106] vs 1314 [n = 105]; P = .03 and 396 [n
      = 106] vs 705 [n = 105]; P = .03, respectively). CONCLUSIONS: Integrated and home
      based geriatric care management resulted in improved quality of care and reduced
      acute care utilization among a high-risk group. Improvements in health-related
      quality of life were mixed and physical function outcomes did not differ between
      groups. Future studies are needed to determine whether more specific targeting
      will improve the program's effectiveness and whether reductions in acute care
      utilization will offset program costs. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00182962.

PMID- 18073359
TI  - Thiazolidinediones and cardiovascular outcomes in older patients with diabetes.
AB  - CONTEXT: Thiazolidinediones (TZDs), used to treat type 2 diabetes, are associated
      with an excess risk of congestive heart failure and possibly acute myocardial
      infarction. However, the association between TZD use and cardiovascular events
      has not been adequately evaluated on a population level. OBJECTIVE: To explore
      the association between TZD therapy and congestive heart failure, acute
      myocardial infarction, and mortality compared with treatment with other oral
      hypoglycemic agents. DESIGN, SETTING, AND PATIENTS: Nested case-control analysis
      of a retrospective cohort study using health care databases in Ontario. We
      included diabetes patients aged 66 years or older treated with at least 1 oral
      hypoglycemic agent between 2002 and 2005 (N = 159 026) and followed them up until
      March 31, 2006. MAIN OUTCOME MEASURES: The primary outcome consisted of an
      emergency department visit or hospitalization for congestive heart failure;
      secondary outcomes were an emergency department visit or hospitalization for
      acute myocardial infarction and all-cause mortality. The risks of these events
      were compared between persons treated with TZDs (rosiglitazone and pioglitazone)
      and other oral hypoglycemic agent combinations, after matching and adjusting for
      prognostic factors. RESULTS: During a median follow-up of 3.8 years, 12 491
      patients (7.9%) had a hospital visit for congestive heart failure, 12,578 (7.9%)
      had a visit for acute myocardial infarction, and 30 265 (19%) died. Current
      treatment with TZD monotherapy was associated with a significantly increased risk
      of congestive heart failure (78 cases; adjusted rate ratio [RR], 1.60; 95%
      confidence interval [CI], 1.21-2.10; P < .001), acute myocardial infarction (65
      cases; RR, 1.40; 95% CI, 1.05-1.86; P = .02), and death (102 cases; RR, 1.29; 95%
      CI, 1.02-1.62; P = .03) compared with other oral hypoglycemic agent combination
      therapies (3478 congestive heart failure cases, 3695 acute myocardial infarction
      cases, and 5529 deaths). The increased risk of congestive heart failure, acute
      myocardial infarction, and mortality associated with TZD use appeared limited to
      rosiglitazone. CONCLUSION: In this population-based study of older patients with
      diabetes, TZD treatment, primarily with rosiglitazone, was associated with an
      increased risk of congestive heart failure, acute myocardial infarction, and
      mortality when compared with other combination oral hypoglycemic agent
      treatments.

PMID- 18073360
TI  - Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction
      in mechanically ventilated patients: the MENDS randomized controlled trial.
AB  - CONTEXT: Lorazepam is currently recommended for sustained sedation of
      mechanically ventilated intensive care unit (ICU) patients, but this and other
      benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and
      coma, associated with prolonged hospital stays, costs, and increased mortality.
      Dexmedetomidine induces sedation via different central nervous system receptors
      than the benzodiazepine drugs and may lower the risk of acute brain dysfunction.
      OBJECTIVE: To determine whether dexmedetomidine reduces the duration of delirium
      and coma in mechanically ventilated ICU patients while providing adequate
      sedation as compared with lorazepam. DESIGN, SETTING, PATIENTS, AND INTERVENTION:
      Double-blind, randomized controlled trial of 106 adult mechanically ventilated
      medical and surgical ICU patients at 2 tertiary care centers between August 2004
      and April 2006. Patients were sedated with dexmedetomidine or lorazepam for as
      many as 120 hours. Study drugs were titrated to achieve the desired level of
      sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients
      were monitored twice daily for delirium using the Confusion Assessment Method for
      the ICU (CAM-ICU). MAIN OUTCOME MEASURES: Days alive without delirium or coma and
      percentage of days spent within 1 RASS point of the sedation goal. RESULTS:
      Sedation with dexmedetomidine resulted in more days alive without delirium or
      coma (median days, 7.0 vs 3.0; P = .01) and a lower prevalence of coma (63% vs
      92%; P < .001) than sedation with lorazepam. Patients sedated with
      dexmedetomidine spent more time within 1 RASS point of their sedation goal
      compared with patients sedated with lorazepam (median percentage of days, 80% vs
      67%; P = .04). The 28-day mortality in the dexmedetomidine group was 17% vs 27%
      in the lorazepam group (P = .18) and cost of care was similar between groups.
      More patients in the dexmedetomidine group (42% vs 31%; P = .61) were able to
      complete post-ICU neuropsychological testing, with similar scores in the tests
      evaluating global cognitive, motor speed, and attention functions. The 12-month
      time to death was 363 days in the dexmedetomidine group vs 188 days in the
      lorazepam group (P = .48). CONCLUSION: In mechanically ventilated ICU patients
      managed with individualized targeted sedation, use of a dexmedetomidine infusion
      resulted in more days alive without delirium or coma and more time at the
      targeted level of sedation than with a lorazepam infusion. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00095251.

PMID- 18073361
TI  - Active smoking and the risk of type 2 diabetes: a systematic review and meta
      analysis.
AB  - CONTEXT: Observational studies have suggested an association between active
      smoking and the incidence of type 2 diabetes. OBJECTIVE: To conduct a systematic
      review with meta-analysis of studies assessing the association between active
      smoking and incidence of type 2 diabetes. DATA SOURCES: A search of MEDLINE (1966
      to May 2007) and EMBASE (1980 to May 2007) databases was supplemented by manual
      searches of bibliographies of key retrieved articles, reviews of abstracts from
      scientific meetings, and contact with experts. STUDY SELECTION: Studies were
      included if they reported risk of impaired fasting glucose, impaired glucose
      tolerance, or type 2 diabetes in relationship to smoking status at baseline; had
      a cohort design; and excluded persons with diabetes at baseline. DATA EXTRACTION
      AND DATA SYNTHESIS: Two authors independently extracted the data, including the
      presence or absence of active smoking at baseline, the risk of diabetes, methods
      used to detect diabetes, and key criteria of study quality. Relative risks (RRs)
      were pooled using a random-effects model. Associations were tested in subgroups
      representing different patient characteristics and study quality criteria.
      RESULTS: The search yielded 25 prospective cohort studies (N = 1.2 million
      participants) that reported 45 844 incident cases of diabetes during a study
      follow-up period ranging from 5 to 30 years. Of the 25 studies, 24 reported
      adjusted RRs greater than 1 (range for all studies, 0.82-3.74). The pooled
      adjusted RR was 1.44 (95% confidence interval [CI], 1.31-1.58). Results were
      consistent and statistically significant in all subgroups. The risk of diabetes
      was greater for heavy smokers (> or =20 cigarettes/day; RR, 1.61; 95% CI, 1.43
      1.80) than for lighter smokers (RR,1.29; 95% CI, 1.13-1.48) and lower for former
      smokers (RR, 1.23; 95% CI, 1.14-1.33) compared with active smokers, consistent
      with a dose-response phenomenon. CONCLUSION: Active smoking is associated with an
      increased risk of type 2 diabetes. Future research should attempt to establish
      whether this association is causal and to clarify its mechanisms.

PMID- 18073362
TI  - Preoperative chemotherapy for breast cancer: miracle or mirage?

PMID- 18073363
TI  - Medical professionalism in a commercialized health care market.

PMID- 18073364
TI  - Health care in the age of genetic medicine.

PMID- 18073365
TI  - Better care for older people with chronic diseases: an emerging vision.

PMID- 18073366
TI  - Smoking and type 2 diabetes: underrecognized risks and disease burden.

PMID- 18073367
TI  - JAMA patient page. Smoking cessation.

PMID- 18073368
TI  - So far, victories are few as breast cancer patients sue Wyeth over hormone
      therapy.

PMID- 18073369
TI  - Lung cancer may be different for men and women, but researchers ponder what to
      do?

PMID- 18073370
TI  - Finding clinical meaning in cancer data.

PMID- 18073371
TI  - Stat bite: Lung cancer incidence by sex.

PMID- 18073372
TI  - Extended adjuvant therapy for breast cancer--how much is enough?

PMID- 18073373
TI  - Genetic and biologic evidence that implicates a gene in aggressive prostate
      cancer.

PMID- 18073374
TI  - Cancer risk of heterozygotes with the NBN founder mutation.
AB  - BACKGROUND: The autosomal recessive chromosomal instability disorder Nijmegen
      breakage syndrome (NBS) is associated with increased risk of lymphoid
      malignancies and other cancers. Cells from NBS patients contain many double
      stranded DNA breaks. More than 90% of NBS patients are homozygous for a founder
      mutation, 657del5, in the NBN gene. We investigated the 657del5 carrier status of
      cancer patients among blood relatives (i.e., first-, through fourth-degree
      relatives) of NBS patients in the Czech Republic and Slovakia to test the
      hypothesis that NBN heterozygotes have an increased cancer risk. METHODS: Medical
      information was compiled from 344 blood relatives of NBS patients in 24 different
      NBS families from January 1, 1998, through December 31, 2003. The 657del5 carrier
      status of subjects was unknown at the time of their recruitment but was later
      determined from blood samples collected at the time of the interview. Medical
      records and death certificates were used to confirm a diagnosis of cancer. For
      the relatives with cancer who are not obligate heterozygotes (such as parents and
      two grandparents in consanguineous families), the observed and expected number of
      mutation carriers were compared by use of the index-test method, which estimated
      the risk of cancer associated with carrying the mutation. All P values were two
      sided. RESULTS: Thirteen of the 344 blood relatives had confirmed cases of any
      type of cancer; 11 of these 13 cancer patients carried the NBN 657del5 mutation,
      compared with 6.0 expected (P = .005). Among the 56 grandparents with complete
      data from 14 NBS families, 10 of the 28 carriers of 657del5, but only one of the
      28 noncarriers, developed cancer (odds ratio = 10.7, 95% CI = 1.4 to 81.5;
      P<.004). CONCLUSIONS: The NBN 657del5 mutation appears to be associated with an
      elevated risk of cancer in heterozygotes.

PMID- 18073375
TI  - Two genome-wide association studies of aggressive prostate cancer implicate
      putative prostate tumor suppressor gene DAB2IP.
AB  - BACKGROUND: The consistent finding of a genetic susceptibility to prostate cancer
      suggests that there are germline sequence variants predisposing individuals to
      this disease. These variants could be useful in screening and treatment. METHODS:
      We performed an exploratory genome-wide association scan in 498 men with
      aggressive prostate cancer and 494 control subjects selected from a population
      based case-control study in Sweden. We combined the results of this scan with
      those for aggressive prostate cancer from the publicly available Cancer Genetic
      Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs)
      that showed statistically significant associations with the risk of aggressive
      prostate cancer based on two-sided allele tests were tested for their association
      with aggressive prostate cancer in two independent study populations composed of
      individuals of European or African American descent using one-sided tests and the
      genetic model (dominant or additive) associated with the lowest value in the
      exploratory study. RESULTS: Among the approximately 60,000 SNPs that were common
      to our study and CGEMS, we identified seven that had a similar (positive or
      negative) and statistically significant (P<.01) association with the risk of
      aggressive prostate cancer in both studies. Analysis of the distribution of these
      SNPs among 1032 prostate cancer patients and 571 control subjects of European
      descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes
      a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was
      associated with aggressive prostate cancer (one-sided P value = .004). The
      association was also statistically significant in an African American study
      population that included 210 prostate cancer patients and 346 control subjects
      (one-sided P value = .02). CONCLUSION: A genetic variant in DAB2IP may be
      associated with the risk of aggressive prostate cancer and should be evaluated
      further.

PMID- 18073376
TI  - Interpreting trends in prostate cancer incidence and mortality in the five Nordic
      countries.
AB  - Trends in incidence and mortality rates of prostate cancer were analyzed using
      data from the national cancer registries of Denmark, Finland, Iceland, Norway,
      and Sweden. Joinpoint regression models were used to quantify temporal trends for
      the period from 1980 to 2004. Incidence rates were increasing and similar in the
      Nordic countries during the 1980s. Around 1990, a more rapid incidence increase
      began in all Nordic countries except Denmark, where an increase was seen 5 years
      later. In 2001, incidence rates in Denmark were half of those seen in the other
      Nordic countries, but mortality rates varied only marginally among countries.
      Mean annual declines in prostate cancer mortality of 1.9% (95% CI = 0.4% to 3.3%)
      and 1.8% (95% CI = 0.5% to 3.0%) were observed from 1996 to 2004 in Finland and
      Norway, respectively. During the same period, mortality rates leveled off in
      Iceland and Sweden but continued to increase in Denmark. The rapid increase in
      incidence during the early 1990s coincided with the introduction of the prostate
      specific antigen (PSA) test and conveys little information about the occurrence
      of potentially lethal disease. Mortality rates, however, have recently stabilized
      or declined in countries where PSA testing and curative treatment have been
      commonly practiced since the late 1980s. Although other explanatory factors may
      be in operation, these trends are consistent with a moderate effect of increased
      curative treatment of early diagnosed prostate cancer and improved treatment of
      more advanced disease.

PMID- 18073377
TI  - Cancer incidence in blood transfusion recipients.
AB  - BACKGROUND: Blood transfusions may influence the recipients' cancer risks both
      through transmission of biologic agents and by modulation of the immune system.
      However, cancer occurrence in transfusion recipients remains poorly
      characterized. METHODS: We used computerized files from Scandinavian blood banks
      to identify a cohort of 888,843 cancer-free recipients transfused after 1968. The
      recipients were followed from first registered transfusion until the date of
      death, emigration, cancer diagnosis, or December 31, 2002, whichever came first.
      Relative risks were expressed as ratios of the observed to the expected numbers
      of cancers, that is, standardized incidence ratios (SIRs), using incidence rates
      for the general Danish and Swedish populations as a reference. All statistical
      tests were two-sided. RESULTS: During 5,652,918 person-years of follow-up, 80,990
      cancers occurred in the transfusion recipients, corresponding to a SIR of 1.45
      (95% confidence interval [CI] = 1.44 to 1.46). The SIR for cancer overall
      decreased from 5.36 (95% CI = 5.29 to 5.43) during the first 6 months after
      transfusion to 1.10 or less for follow-up periods more than 2 years after the
      transfusion. However, the standardized incidence ratios for cancers of the
      tongue, mouth, pharynx, esophagus, liver, and respiratory and urinary tracts and
      for squamous cell skin carcinoma remained elevated beyond 10 years after the
      transfusion. CONCLUSIONS: The marked increase in cancer risk shortly after a
      blood transfusion may reflect the presence of undiagnosed occult cancers with
      symptoms that necessitated the blood transfusion. The continued increased risk of
      tobacco- and alcohol-related cancers suggests that lifestyle and other risk
      factors related to conditions prompting transfusion rather than transfusion
      related exposures per se are important to the observed cancer occurrence in the
      recipients.

PMID- 18073378
TI  - Extended adjuvant therapy with anastrozole among postmenopausal breast cancer
      patients: results from the randomized Austrian Breast and Colorectal Cancer Study
      Group Trial 6a.
AB  - BACKGROUND: Clinical trial data have shown that among breast cancer patients who
      were disease free after 5 years of adjuvant treatment with tamoxifen, further
      extended treatment with the nonsteroidal aromatase inhibitor letrozole reduces
      breast cancer recurrence. We examined the efficacy and tolerability of extended
      adjuvant therapy with another aromatase inhibitor, anastrozole, for 3 years among
      women who had completed 5 years of adjuvant therapy. METHODS: Austrian Breast and
      Colorectal Cancer Study Group (ABCSG) Trial 6a is an extension of ABCSG Trial 6,
      in which hormone receptor-positive postmenopausal patients received 5 years of
      adjuvant tamoxifen, with or without the aromatase inhibitor aminoglutethimide,
      for the first 2 years of therapy. For ABCSG Trial 6a, patients who were disease
      free at the end of Trial 6 were randomly assigned to receive either 3 years of
      anastrozole or no further treatment. Efficacy data were analyzed with the use of
      a Cox proportional hazards regression model with two-sided P values and Kaplan
      Meier curves, and tolerability data were estimated using logistic regression
      analysis with odds ratios and 95% confidence intervals (CIs). RESULTS: ABCSG
      Trial 6a included 856 patients. At a median follow-up of 62.3 months, women who
      received anastrozole (n = 387) had a statistically significantly reduced risk of
      recurrence (locoregional recurrence, contralateral breast cancer, or distant
      metastasis) compared with women who received no further treatment (n = 469;
      hazard ratio = 0.62; 95% CI = 0.40 to 0.96, P = .031). Anastrozole was well
      tolerated, and no unexpected adverse events were reported. CONCLUSIONS: These
      data confirm the benefit of extending adjuvant tamoxifen therapy beyond 5 years
      with anastrozole compared with no further treatment. Further research is required
      to define the optimum length of extended adjuvant therapy and to investigate the
      possibility of tailoring this period to suit different disease types.

PMID- 18073379
TI  - Radiologist characteristics associated with interpretive performance of
      diagnostic mammography.
AB  - BACKGROUND: Extensive variability has been noted in the interpretive performance
      of screening mammography; however, less is known about variability in diagnostic
      mammography performance. METHODS: We examined the performance of 123 radiologists
      who interpreted 35895 diagnostic mammography examinations that were obtained to
      evaluate a breast problem from January 1, 1996, through December 31, 2003, at 72
      facilities that contribute data to the Breast Cancer Surveillance Consortium. We
      modeled the influence of radiologist characteristics on the sensitivity and false
      positive rate of diagnostic mammography, adjusting for patient characteristics by
      use of a Bayesian hierarchical logistic regression model. RESULTS: The median
      sensitivity was 79% (range = 27%-100%) and the median false-positive rate was
      4.3% (range = 0%-16%). Radiologists in academic medical centers, compared with
      other radiologists, had higher sensitivity (88%, 95% confidence interval [CI] =
      77% to 94%, versus 76%, 95% CI = 72% to 79%; odds ratio [OR] = 5.41, 95% Bayesian
      posterior credible interval [BPCI] = 1.55 to 21.51) with a smaller increase in
      their false-positive rates (7.8%, 95% CI = 4.8% to 12.7%, versus 4.2%, 95% CI =
      3.8% to 4.7%; OR = 1.73, 95% BPCI = 1.05 to 2.67) and a borderline statistically
      significant improvement in accuracy (OR = 3.01, 95% BPCI = 0.97 to 12.15).
      Radiologists spending 20% or more of their time on breast imaging had
      statistically significantly higher sensitivity than those spending less time on
      breast imaging (80%, 95% CI = 76% to 83%, versus 70%, 95% CI = 64% to 75%; OR =
      1.60, 95% BPCI = 1.05 to 2.44) with non-statistically significant increased false
      positive rates (4.6%, 95% CI = 4.0% to 5.3%, versus 3.9%, 95% CI = 3.3% to 4.6%;
      OR = 1.17, 95% BPCI = 0.92 to 1.51). More recent training in mammography and more
      experience performing breast biopsy examinations were associated with a decreased
      threshold for recalling patients, resulting in similar statistically significant
      increases in both sensitivity and false-positive rates. CONCLUSIONS: We found
      considerable variation in the interpretive performance of diagnostic mammography
      across radiologists that was not explained by the characteristics of the patients
      whose mammograms were interpreted. This variability is concerning and likely
      affects many women with and without breast cancer.

PMID- 18073380
TI  - Wolbachia genome integrated in an insect chromosome: evolution and fate of
      laterally transferred endosymbiont genes.
AB  - Recent accumulation of microbial genome data has demonstrated that lateral gene
      transfers constitute an important and universal evolutionary process in
      prokaryotes, while those in multicellular eukaryotes are still regarded as
      unusual, except for endosymbiotic gene transfers from mitochondria and plastids.
      Here we thoroughly investigated the bacterial genes derived from a Wolbachia
      endosymbiont on the nuclear genome of the beetle Callosobruchus chinensis.
      Exhaustive PCR detection and Southern blot analysis suggested that approximately
      30% of Wolbachia genes, in terms of the gene repertoire of wMel, are present on
      the insect nuclear genome. Fluorescent in situ hybridization located the
      transferred genes on the proximal region of the basal short arm of the X
      chromosome. Molecular evolutionary and other lines of evidence indicated that the
      transferred genes are probably derived from a single lateral transfer event. The
      transferred genes were, for the length examined, structurally disrupted, freed
      from functional constraints, and transcriptionally inactive. Hence, most, if not
      all, of the transferred genes have been pseudogenized. Notwithstanding this, the
      transferred genes were ubiquitously detected from Japanese and Taiwanese
      populations of C. chinensis, while the number of the transferred genes detected
      differed between the populations. The transferred genes were not detected from
      congenic beetle species, indicating that the transfer event occurred after
      speciation of C. chinensis, which was estimated to be one or several million
      years ago. These features of the laterally transferred endosymbiont genes are
      compared with the evolutionary patterns of mitochondrial and plastid genome
      fragments acquired by nuclear genomes through recent endosymbiotic gene
      transfers.

PMID- 18073381
TI  - Uncertainty in homology inferences: assessing and improving genomic sequence
      alignment.
AB  - Sequence alignment underpins all of comparative genomics, yet it remains an
      incompletely solved problem. In particular, the statistical uncertainty within
      inferred alignments is often disregarded, while parametric or phylogenetic
      inferences are considered meaningless without confidence estimates. Here, we
      report on a theoretical and simulation study of pairwise alignments of genomic
      DNA at human-mouse divergence. We find that >15% of aligned bases are incorrect
      in existing whole-genome alignments, and we identify three types of alignment
      error, each leading to systematic biases in all algorithms considered. Careful
      modeling of the evolutionary process improves alignment quality; however, these
      improvements are modest compared with the remaining alignment errors, even with
      exact knowledge of the evolutionary model, emphasizing the need for statistical
      approaches to account for uncertainty. We develop a new algorithm, Marginalized
      Posterior Decoding (MPD), which explicitly accounts for uncertainties, is less
      biased and more accurate than other algorithms we consider, and reduces the
      proportion of misaligned bases by a third compared with the best existing
      algorithm. To our knowledge, this is the first nonheuristic algorithm for DNA
      sequence alignment to show robust improvements over the classic Needleman-Wunsch
      algorithm. Despite this, considerable uncertainty remains even in the improved
      alignments. We conclude that a probabilistic treatment is essential, both to
      improve alignment quality and to quantify the remaining uncertainty. This is
      becoming increasingly relevant with the growing appreciation of the importance of
      noncoding DNA, whose study relies heavily on alignments. Alignment errors are
      inevitable, and should be considered when drawing conclusions from alignments.
      Software and alignments to assist researchers in doing this are provided at
      http://genserv.anat.ox.ac.uk/grape/.

PMID- 18073382
TI  - Type I interferons as anti-inflammatory mediators.
AB  - The type I interferons (IFNs), IFN-alpha and IFN-beta, are cytokines that have
      antiviral, antiproliferative, and immunomodulatory activities. Data are now
      emerging that suggest that type I IFNs are also important mediators of anti
      inflammatory responses. These findings, largely driven by studies to explain the
      beneficial effects of IFN-beta in the treatment of multiple sclerosis, an
      autoimmune disease of the central nervous system, offer a number of mechanisms
      for the anti-inflammatory properties of type I IFNs. Type I IFNs, through their
      ability to induce the immunosuppressive cytokine interleukin-10 (IL-10), mediate
      the inhibition of proinflammatory gene products. In addition, type I IFNs induce
      other immunosuppressive mediators such as suppressor of cytokine signaling-1
      (SOCS-1) and tristetrapolin (TTP), which act by divergent mechanisms to restore
      homeostasis to the immune system. Furthermore, type I IFNs mediate anti
      inflammatory and protective effects in a variety of autoimmune disease models
      such as experimental colitis, experimental allergic encephalomyelitis,
      experimental arthritis, and neonatal inflammation. Here, we discuss the molecular
      basis for the anti-inflammatory properties of type I IFNs and their therapeutic
      potential in autoimmune and inflammatory diseases.

PMID- 18073383
TI  - Putting on the RITz.
AB  - Neurons develop two types of processes, axons and dendrites, whose growth must be
      independently controlled. Recent research has identified the small guanosine
      triphosphatase Rit as a differential regulator of neurite growth. Activation of
      Rit enhances axonal growth, whereas inhibition of Rit promotes dendritic growth.
      These results imply that the reciprocal regulation of a single molecule in the
      same cell can achieve simultaneous regulation of axonal and dendritic growth.

PMID- 18073384
TI  - A discrete signaling function for an inositol pyrophosphate.
AB  - Inositol pyrophosphates were, until recently, without clearly defined functions.
      Two recent papers in Science have now clearly defined a function for an IP(7)
      pyrophosphate (inositol hexaphosphate with one pyrophosphate) that is the product
      of the enzyme encoded by the Vip1 gene in Saccharomyces cerevisiae. This IP(7)
      with a pyrophosphate tentatively assigned to be on either the 4 or 6 position is
      a cofactor that is required for inactivating the cyclin-cyclin-dependent kinase
      complex of Pho80, Pho81, and Pho85. Inhibition of the kinase results in the
      nuclear translocation of Pho4, which is a transcription factor that promotes
      expression of genes required for phosphate assimilation under conditions of low
      phosphate. When grown in low-phosphate media, IP(7) accumulates, which leads to
      the expression of genes involved in the acquisition of phosphate.

PMID- 18073385
TI  - Mitochondrial complexes in Trypanosoma brucei: a novel complex and a unique
      oxidoreductase complex.
AB  - African trypanosomes, early diverged eukaryotes and the agents of sleeping
      sickness, have several basic cellular processes that are remarkably divergent
      from those in their mammalian hosts. They have large mitochondria and switch
      between oxidative phosphorylation and glycolysis as the major pathways for energy
      generation during their life cycle. We report here the identification and
      characterization of several multiprotein mitochondrial complexes from procyclic
      form Trypanosoma brucei. These were identified and purified using a panel of
      monoclonal antibodies that were generated against a submitochondrial protein
      fraction and using tandem affinity purification (TAP) tag affinity chromatography
      and localized within the cells by immunofluorescence. Protein composition
      analyses by mass spectrometry revealed substantial divergence of oxidoreductase
      complex from that of other organisms and identified a novel complex that may have
      a function associated with nucleic acids. The relationship to divergent
      physiological processes in these pathogens is discussed.

PMID- 18073386
TI  - Exacerbation-free COPD: a goal too far?
AB  - The seventh Lund COPD workshop focused on exacerbations. As chronic obstructive
      pulmonary disease (COPD) progresses, exacerbations, events characterized by acute
      worsening of symptoms, increase in frequency and severity. Patients fear their
      occurrence, as they compromise function and quality of life, may require
      admission to the hospital, and can be fatal. There are therapies that improve
      outcome of exacerbations, such as antibiotics and corticosteroids. More
      importantly, some treatments, such as regular inhaled bronchodilator therapy
      (particularly with long-acting agents), inhaled corticosteroids, and vaccination
      against influenza virus, can partially prevent attacks. However, exacerbations
      remain a challenge, as no therapy effectively banishes them. The current
      symposium, "Exacerbation-free COPD, a goal too far?", was designed to address
      this problem. The challenge addressed by the participants was whether more
      effective treatments could be developed that could further eliminate COPD
      exacerbations.

PMID- 18073387
TI  - Exacerbations in chronic obstructive pulmonary disease: do they contribute to
      disease progression?
AB  - The impact of chronic obstructive pulmonary disease (COPD) exacerbations on
      decline in FEV(1) has been a controversial topic for decades. We will review some
      of the key studies in this area and discuss potential contributors to
      inconsistent results of these studies. Dissecting the heterogeneous COPD syndrome
      into meaningful subtypes and assessing the genetic and environmental influences
      on COPD-related phenotypes such as exacerbation frequency could clarify the
      impact of exacerbations on the natural history of COPD.

PMID- 18073388
TI  - The similarities and differences of epidemic cycles of chronic obstructive
      pulmonary disease and asthma exacerbations.
AB  - The majority of chronic obstructive pulmonary disease (COPD) and asthma
      exacerbations in both children and adults are associated with respiratory viral
      infections and are cyclic in nature. Some variation in these cycles is associated
      with the timing of the appearance of respiratory viruses, particularly influenza
      and respiratory syncytial virus. Much more, however, is associated with signal
      events that are of either fixed or predictable timing. In children, asthma
      exacerbations reach epidemic levels following school return after the summer
      vacation and these are predominantly associated with rhinovirus infections.
      Although younger adults experience a rise in asthma exacerbations at this time,
      these are secondary to the epidemic in children. Older adults with either COPD or
      asthma experience only a slightly elevated risk of exacerbations after school
      return, and hospital presentations for pneumonia in any age group show only
      marginal increases at that time. Exacerbations of both COPD and adult asthma,
      with increasing risk with age, are at their highest average annual levels during
      the Christmas period. This effect appears to be independent of the timing of
      above average levels of influenza, RSV, parainfluenza, or adenovirus detections;
      however, hospitalization for respiratory tract infections in all age groups
      reaches high levels at the same time. Both the post-summer vacation asthma
      epidemic and the Christmas epidemic of COPD, asthma, and pneumonia are
      synchronous with the timing of signal events, the day of school return for the
      former and Christmas Day for the latter, and have been for several years. The
      agents responsible for the Christmas epidemic of respiratory diseases have not
      yet been identified. The differences between age and disease exacerbation
      patterns after school return and at Christmas suggest that either different
      agents are involved or that the response to a common agent is different between
      the two signal events.

PMID- 18073389
TI  - Quantifying of severity of exacerbations in chronic obstructive pulmonary
      disease: adaptations to the definition to allow quantification.
AB  - Exacerbations of chronic obstructive pulmonary disease (COPD) offer a
      considerable clinical challenge for clinical practice and drug development. The
      underlying pathobiology of these characteristic events is unclear. We are far
      behind other disease areas, such as cardiology, where there are effective
      approaches for diagnosing and managing acute and potentially fatal events. A
      joint initiative has begun between the pharmaceutical industry, academia, and the
      Food and Drug Administration to produce a valid diary card measure of
      exacerbation severity: the EXAcerbations of Chronic pulmonary disease Test
      Patient-Reported Outcome (EXACT-PRO). This article describes the background to
      this initiative, using the consensus definition of a COPD exacerbation as the
      starting point from which to propose a new method for quantifying the severity of
      the event. This approach takes into account the relationships between the
      symptoms that make up an exacerbation and shows that they can be used in a single
      continuous severity scale. Methods for defining exacerbation onset and cessation
      are also proposed.

PMID- 18073390
TI  - Structural and functional co-conspirators in chronic obstructive pulmonary
      disease exacerbations.
AB  - Chronic obstructive pulmonary disease (COPD) exacerbations have a major impact on
      patients with COPD, yet they are complex events that are associated with a number
      of triggers and affected by the underlying disease process. A number of
      conditions can mimic the symptoms of an exacerbation and require evaluation.
      Airway and systemic inflammatory changes at exacerbation are modulated by
      infective factors (viruses and bacteria) and lead to the pathophysiologic effects
      seen at exacerbations with increase in airflow obstruction. Although bacteria or
      viruses can be isolated at exacerbation, often these organisms act in combination
      and lead to greater inflammatory changes and more severe exacerbation. Underlying
      structural changes such as radiologic changes of bronchiectasis that can be found
      in COPD can also modulate exacerbation severity and contribute to morbidity
      associated with exacerbations.

PMID- 18073391
TI  - Practical and conceptual models of chronic obstructive pulmonary disease.
AB  - The challenges of chronic obstructive pulmonary disease and the difficulties in
      modeling its pathology in vitro and in vivo are substantial. Integration of
      innate- and adaptive-type responses with processes of scarring and healing do not
      fit comfortably with some definitions of the immune system, and, instead, this
      disease is an exemplar of a network-based system that we have named "contiguous
      immunity." The complicated and highly interconnected networks underpinning many
      biological processes show features of scale-free networks. Consideration of
      chronic obstructive pulmonary disease pathology as a scale-free network showing
      features of contiguous immunity might, in the future, aid identification and
      targeting of potential key "hubs"-these being principal components of the disease
      network-manipulation of which may yield successful new therapies.

PMID- 18073392
TI  - The interaction of host and pathogen factors in chronic obstructive pulmonary
      disease exacerbations and their role in tissue damage.
AB  - Inflammation plays a central role in the development and progression of chronic
      obstructive pulmonary disease (COPD). Host factors, such as proteinases and
      oxidants, have been implicated in causing tissue damage and amplifying the
      inflammatory process. During exacerbations of COPD, inflammation, oxidant stress,
      and many of these proteinases are increased. The role of bacteria in exacerbation
      remains unclear; however, many bacterial factors, such as proteases, surface
      proteins, lipopoly(oligo)saccharide, and pyocyanin, may also damage lung tissue
      either directly or by promoting the host inflammatory response. The interaction
      between host and bacterial factors is complex and both can cause similar damage,
      making it difficult to dissect the relative contribution of each factor. There
      have been few relevant studies in man; however, most of the available evidence
      relates to the importance of the host response. To resolve this issue, several
      steps are required. Lung secretions need to be collected from patients in the
      stable clinical state as well as during well defined exacerbations involving
      bacteria. The appropriate factors need to be identified in the secretions and
      require evidence that they are functionally active. Specific abrogation should
      then change the overall balance within the local environment, after which the
      administration of specific inhibitors/antagonists can be used to confirm that the
      factor being studied is central to the inflammatory cascade and subsequent tissue
      damage in patients. Finally, controlled clinical trials will be required to
      demonstrate that modifying inflammation influences long-term progression.

PMID- 18073394
TI  - Systemic inflammation in chronic obstructive pulmonary disease: the role of
      exacerbations.
AB  - The systemic manifestations of chronic obstructive pulmonary disease (COPD)
      exacerbations are recognized, but our understanding of their etiology and
      importance is lacking largely due to the small number of systematic and
      longitudinal studies. Most of the systemic manifestations are likely the result
      of inflammatory processes. Serum biomarkers, such as various cytokines,
      adipokines, C-reactive protein, and coagulation factors, are elevated during
      exacerbations. Our understanding of the systemic manifestations can be greatly
      enhanced if we integrate what is known about the basic science of systemic
      mediators with the translational science of their role in COPD exacerbations.
      Many overlapping connections and promising avenues of future research come to
      light with such a viewpoint.

PMID- 18073393
TI  - Respiratory infections: do we ever recover?
AB  - Although the outcome of respiratory infection alters with age, nutritional
      status, and immunologic competence, there is a growing body of evidence that we
      all develop a unique but subtle inflammatory profile. This uniqueness is
      determined by the sequence of infections or antigenic insults encountered that
      permanently mold our lungs through experience. This experience and learning
      process forms the basis of immunologic memory that is attributed to the acquired
      immune system. But what happens if the pathogen is not homologous to any
      preceding it? In the absence of cross-specific acquired immunity, one would
      expect a response similar to that of a subject who had never been infected with
      anything before. It is now clear that this is not the case. Prior inflammation in
      the respiratory tract alters immunity and pathology to subsequent infections even
      when they are antigenically distinct. Furthermore, the influence of the first
      infection is long lasting, not dependent on the presence of T and B cells, and
      effective against disparate pathogen combinations. We have used the term "innate
      imprinting" to explain this phenomenon, although innate education may be a closer
      description. This educational process, by sequential waves of infection, may be
      beneficial, as shown for successive viral infections, or significantly worse, as
      illustrated by the increased susceptibly to life-threatening bacterial pneumonia
      in patients infected with seasonal and pandemic influenza. We now examine what
      these long-term changes involve, the likely cell populations affected, and what
      this means to those studying inflammatory disorders in the lung.

PMID- 18073395
TI  - Toll-like receptors, Notch ligands, and cytokines drive the chronicity of lung
      inflammation.
AB  - Current dogma supports the concept that the expression of a disease-inducing
      signature cytokine phenotype is important to the maintenance stage of chronic
      lung disorders. This cytokine phenotype has been characterized as a polarization
      toward type 2 cytokines, which are profibrotic and immunoregulatory. The biology
      of this latter activity could mechanistically explain pathogen-induced
      exacerbation of chronic lung inflammation, as a skewed cytokine profile in the
      lung alters dendritic cell function, activates fibroblasts, and facilitates a
      subsequent "second hit" by an infectious pathogen. In this setting, cytokine
      biology is also linked to Toll-like receptors (TLRs) in the maintenance of lung
      immunity, as the activity of this receptor-ligand system by both leukocytes and
      stromal cells is likely an important component of disease chronicity. The
      participation of dendritic cells via TLRs in chronic lung disease could
      facilitate communication circuits established between antigen-presenting cells
      and lymphocytes. Data suggest that TLR activation via myeloid differentiation
      factor 88 adaptor protein leads to the induction of a Notch ligand known as Delta
      like-4 on dendritic cells that activate the Notch receptor on T cells, promoting
      a helper T-cell type 1 cytokine response. It is likely that the evolution of host
      defense signals designed to recognize patterns emitted from a hostile microbial
      environment may now be superimposed on adaptive immunity and provide the
      underpinning to support the maintenance of chronic lung disease.

PMID- 18073396
TI  - Diagnosis of pathogens in exacerbations of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is increasing in prevalence. Acute
      exacerbations of COPD are the major cause worldwide of morbidity, mortality, and
      health care costs as well as decreased quality of life for the individual. The
      majority of exacerbations are infectious in etiology. Bacteria are detected in
      50% of exacerbations and polymerase chain reaction techniques have established
      that, in half to two-thirds of exacerbations, viruses are causative pathogens.
      Combined bacterial and viral infection can be identified in 25% of exacerbations
      and these dual infections are often more severe. Despite occurring frequently,
      the mechanisms by which infection with these pathogens causes exacerbations are
      incompletely understood. This highlights the need for continued research, because
      a greater understanding of the mechanism of COPD exacerbations may lead to
      identification of potential targets for the development of therapeutic options
      for this increasingly common condition.

PMID- 18073398
TI  - Future treatment to lessen exacerbations of chronic obstructive pulmonary
      disease.
AB  - Therapies currently used to reduce exacerbations of chronic obstructive pulmonary
      disease (COPD) are compounds used almost entirely for asthma therapy. A notable
      exception is tiotropium, a long-acting parasympatholytic agent. This compound and
      its precursor, iprotropium, are only occasionally used for asthma therapy.
      Likewise, leukotriene-modifying drugs are used occasionally for the treatment of
      COPD. In neither circumstance is there agency-approved indication for these
      particular cross-over therapies, but the use of long-acting beta(2)-adrenergic
      compounds and high-solubility inhaled steroids is a mainstay for therapy in both
      asthma and COPD. Similarly, theophylline, although less often used for either
      process, is therapeutically applicable to both asthma and COPD. Although overlap
      syndromes point to the occurrence of a common pathway in some cases, the
      inflammatory process for asthma and chronic obstructive pulmonary disease (COPD)
      differs substantially in most cases. Hence, the application of therapies designed
      to relax airway smooth muscle and ameliorate asthmatic inflammation lacks a
      therapeutic rationale for a disease characterized by predominant neutrophilic
      inflammation occurring in the small airways and alveoli. By definition, COPD is
      poorly reversible airflow obstruction; hence, the use of drugs designed to relax
      airway smooth muscle is somewhat counterintuitive and does not address the
      pathophysiological process of the disease.

PMID- 18073399
TI  - The tip of the "ICEBERGS": a National Conference to Combat the Growing Global
      Epidemic of COPD in women.

PMID- 18073397
TI  - Pathogen-directed therapy in acute exacerbations of chronic obstructive pulmonary
      disease.
AB  - Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important
      events in the natural history of this chronic lung disorder. These events can be
      caused by a large number of infectious and noninfectious agents and are
      associated with an increased local and systemic inflammatory response. Their
      frequency and severity have been linked to progressive deterioration in lung
      function and health status. Infectious pathogens ranging from viral to atypical
      and typical bacteria have been implicated in the majority of episodes. Most
      therapeutic regimens to date have emphasized broad, nonspecific approaches to
      bronchoconstriction and pulmonary inflammation. Increasingly, therapy that
      targets specific etiologic pathogens has been advocated. These include clinical
      and laboratory-based methods to identify bacterial infections. Further additional
      investigation has suggested specific pathogens within this broad class. As
      specific antiviral therapies become available, better diagnostic approaches to
      identify specific pathogens will be required. Furthermore, prophylactic therapy
      for at-risk individuals during high-risk times may become a standard therapeutic
      approach. As such, the future will likely include aggressive diagnostic
      algorithms based on the combination of clinical syndromes and rapid laboratory
      modalities to identify specific causative bacteria or viruses.

PMID- 18073400
TI  - Understanding the biological differences in susceptibility to chronic obstructive
      pulmonary disease between men and women.
AB  - There is a worldwide epidemic of chronic obstructive pulmonary disease (COPD) in
      women. Some large epidemiologic studies suggest that female smokers may have
      increased susceptibility to COPD. The biological mechanisms to explain these
      observations are far from certain. However, the susceptibility to the effects of
      cigarette smoke in women could be due to a greater deposition of toxic substances
      in the lung, impaired clearance of the toxins that are deposited, and/or an
      exaggerated biologic response to these toxins. The latter effect could be due to
      an increased ability to convert certain xenobiotics to more toxic metabolites or
      to a decreased ability to conjugate and excrete metabolites of these toxins.
      Female hormones, in particular estrogen, can up-regulate certain cytochrome P450
      enzymes without altering detoxifying enzymes, leading to a disturbance in the
      balance between metabolism and conjugation. This article reviews this and other
      potential mechanisms that may confer increased susceptibility of COPD to female
      smokers.

PMID- 18073401
TI  - Tobacco use, women, gender, and chronic obstructive pulmonary disease: are the
      connections being adequately made?
AB  - This article reflects on a multidisciplinary workshop addressing the evidence
      pertaining to tobacco use, sex, gender, and chronic obstructive pulmonary disease
      (COPD). In preparation, a literature review was conducted that examined the
      academic and gray literature on tobacco, COPD, and gender and women, with a view
      to assessing if and how these literatures spoke to each other. These materials
      were discussed in a sponsored workshop (Toward a Research Agenda on Gender and
      Chronic Obstructive Pulmonary Disease) held in Vancouver, Canada, in 2007,
      engaging a variety of scientists and stakeholders in assessing the issues and
      emergent questions. The goal of this workshop was to foster the advancement of a
      research agenda that more tightly links tobacco, COPD, and lung health and that
      reflects and investigates sex and gender issues, especially in reference to the
      growing rates of COPD among women. A research agenda for consideration by
      researchers in the fields of women's health, medicine, tobacco use, COPD, and
      related fields is offered.

PMID- 18073402
TI  - Understanding the social consequences of chronic obstructive pulmonary disease:
      the effects of stigma and gender.
AB  - Stigma is a social construction that defines people in terms of a distinguishing
      characteristic or mark, and devalues them as a consequence. Stigma occurs when
      society labels someone as tainted, less desirable, or handicapped. There is
      emerging evidence that chronic obstructive pulmonary disease (COPD) is a physical
      condition with social consequences. The valuing, and devaluing, of individuals
      within society are social judgments that have roots in sociocultural values and
      beliefs. Cultural norms and values dictate the distinct roles and behaviors that
      are expected of men and women in a given culture. Social reactions to individuals
      with COPD can have an effect on their illness experience. This article explores
      the relationships between COPD and stigma and gender, particularly how these key
      elements may interact to affect experiences of individuals with COPD within their
      social milieu. The aim of this article is to begin to set out questions and
      issues that require further empirical exploration. The stigma of COPD arises
      because people are held responsible for their disease, are noted to have engaged
      in a stigmatized behavior (smoking), are marked with oxygen equipment and bodily
      changes, and experience a disruption in their social interactions.

PMID- 18073403
TI  - Reflecting the changing face of chronic obstructive pulmonary disease: sex and
      gender in public education materials on COPD.
AB  - Emerging evidence suggests that sex and gender differences exist in the
      prevalence, susceptibility to, severity of, and response to treatment and
      management of, chronic obstructive pulmonary disease (COPD). However, the
      identification of knowledge gaps regarding sex, gender, and COPD involves not
      only pinpointing what areas of etiology, epidemiology, and management need to be
      examined from a sex and gender perspective (as discussed in other articles of
      this issue), but also must include discussion of how such new and emerging
      findings are translated to health care professionals, policy makers, and the
      general population. How emerging knowledge is reflected in educational, awareness
      raising, and policy materials made available to the public through community
      based organizations, lung health advocacy organizations, the government, and
      clinicians is not known. A preliminary examination of such documents from around
      the world suggests that many materials continue to present COPD as a disease that
      primarily afflicts men. This gap in the translation of research knowledge may be
      specifically problematic for women-for example, because they may not be
      adequately informed of the symptoms of COPD, be appropriately screened for the
      disease, or receive appropriate interventions and treatment.

PMID- 18073404
TI  - Gender and the diagnosis, management, and surveillance of chronic obstructive
      pulmonary disease.
AB  - Following in the footsteps of cardiovascular researchers and clinicians, the
      pulmonary scientific community is beginning to explore how gender may impact the
      diagnosis, treatment, and surveillance of chronic obstructive pulmonary disease
      (COPD). Investigators and clinicians in this field are tackling the complex
      questions surrounding how differences in male/female biology may interact with
      gender differences in environmental, societal, cultural, and behavioral
      determinants of health to influence outcomes in COPD. In this article, issues
      such as gender differences in symptoms, gender diagnostic bias, differential
      impact of therapies, including smoking cessation and pharmacologic management, as
      well as the impact of these issues on COPD surveillance, are discussed. Current
      knowledge from the literature coupled with discussions from a 1-day symposium on
      gender and COPD diagnosis, management, and surveillance are detailed, including
      recommendations on where future research endeavors may be targeted.

PMID- 18073405
TI  - Environmental and occupational exposures: do they affect chronic obstructive
      pulmonary disease differently in women and men?
AB  - This workshop summary examines current research that addresses the question: Are
      women more susceptible than men to the effects of inhaled pollutants, namely
      those found in work or residential environments? A systematic literature review
      was performed in preparation for the workshop. A total of 73 recent (since 2000)
      articles were retrieved reporting on occupational and environmental exposures and
      their impact on chronic obstructive pulmonary disease, of which only nine
      provided gender-stratified results. In two mortality studies, results were
      contrary (one finding increased chronic obstructive pulmonary disease mortality
      in relation to traffic among elderly women compared with men, the other finding
      no gender difference). Two other environmental studies suggested small gender
      differences with slightly greater effect of biomass or traffic-related pollution
      among women. Four of five occupational studies also found increased effects of
      workplace pollutant exposure on measures of chronic airflow obstruction or
      bronchitis symptoms in women; again the differences were small. Preliminary
      findings from analysis of pooled data from six cross-sectional occupational
      surveys by our team also indicated increased relative risk for airflow
      obstruction in relation to work in industrial or service jobs among women
      compared with men, but only when airflow obstruction was measured using a gender
      specific approach to determining the lower limit of normal. Workshop participants
      identified five key gaps and research needs, including the development of gender
      sensitive tools for conducting future research in this area.

PMID- 18073406
TI  - Ceramide synthesis in the endoplasmic reticulum can permeabilize mitochondria to
      proapoptotic proteins.
AB  - Increased mitochondrial ceramide levels are associated with the initiation of
      apoptosis. There is evidence that ceramide is causal. Thus, the conversion of the
      precursor, dihydroceramide, to ceramide by the enzyme dihydroceramide desaturase
      may be important in preparing the cell for apoptosis. Ceramide can initiate
      apoptosis by permeabilizing the mitochondrial outer membrane to apoptosis
      inducing proteins. However, the mitochondrion's ability to produce ceramide may
      be limited by its proteome. Here, we show that ceramide synthesized in isolated
      mammalian endoplasmic reticulum (ER) vesicles from either C8-dihydroceramide or
      sphingosine to produce long-chain ceramide can transfer to isolated mitochondria.
      The rate of transfer is consistent with a simple collision model. The transfer of
      the long-chain ceramide is faster than expected for an uncatalyzed process.
      Sufficient ceramide is transferred to permeabilize the outer membrane to
      cytochrome c and adenylate kinase. The mitochondria-associated membranes, ER-like
      membranes that are tightly associated with isolated mitochondria, can produce
      enough ceramide to permeabilize the outer membrane transiently. Thus, this
      ceramide exchange obviates the need for a complete ceramide de novo pathway in
      mitochondria to increase ceramide levels to the critical value required for
      functional changes, such as ceramide channel self-assembly followed by protein
      release.

PMID- 18073407
TI  - The International Union of Physiological Sciences IUPS Editorial IV.

PMID- 18073408
TI  - In vivo calcium imaging of neural network function.
AB  - Spatiotemporal activity patterns in local neural networks are fundamental to
      brain function. Network activity can now be measured in vivo using two-photon
      imaging of cell populations that are labeled with fluorescent calcium indicators.
      In this review, we discuss basic aspects of in vivo calcium imaging and highlight
      recent developments that will help to uncover operating principles of neural
      circuits.

PMID- 18073409
TI  - Fusion, fission, and secretion during phagocytosis.
AB  - Phagocytosis is essential for the elimination of pathogens and for clearance of
      apoptotic bodies. The ingestion process entails extensive remodeling of the
      cellular membranes, particularly when large and/or multiple particles are
      engulfed. The membrane fusion and fission events that accompany phagocytosis are
      described. The coordinated sequence of membrane trafficking events required for
      phagocytosis involves multiple organelles and also serves other cellular
      functions, such as cytokine secretion.

PMID- 18073410
TI  - Metabolic control of proteasome function.
AB  - Proteasomes are major cellular proteases that are important for protein turnover
      and cell survival. Dysregulation of proteasome is related to many major human
      diseases. Regulation of the proteasome is beginning to be understood by the
      recent findings that proteasomes are modified and regulated by metabolic factors
      O-GlcNAcylation and PKA phosphorylation.

PMID- 18073411
TI  - The role of shear stress on ET-1, KLF2, and NOS-3 expression in the developing
      cardiovascular system of chicken embryos in a venous ligation model.
AB  - In this review, the role of wall shear stress in the chicken embryonic heart is
      analyzed to determine its effect on cardiac development through regulating gene
      expression. Therefore, background information is provided for fluid dynamics,
      normal chicken and human heart development, cardiac malformations, cardiac and
      vitelline blood flow, and a chicken model to induce cardiovascular anomalies. A
      set of endothelial shear stress-responsive genes coding for endothelin-1 (ET-1),
      lung Kruppel-like factor (LKLF/KLF2), and endothelial nitric oxide synthase
      (eNOS/NOS-3) are active in development and are specifically addressed.

PMID- 18073412
TI  - Tandem mass spectrometry in physiology.
AB  - Tandem mass spectrometry coupled to liquid chromatography (LC-MS/MS) allows
      identification of proteins in a complex mixture without need for protein
      purification ("shotgun" proteomics). Recent progress in LC-MS/MS-based
      quantification, phosphoproteomic analysis, and targeted LC-MS/MS using multiple
      reaction monitoring (MRM) has made LC-MS/MS a powerful tool for the study of cell
      physiology.

PMID- 18073413
TI  - The role of matrix metalloproteinases in stromal/epithelial interactions in the
      gut.
AB  - The gastrointestinal mucosa is an extremely soft, highly vascularised tissue,
      with a single layer of epithelium separating the gut lumen from the host.
      Epithelial cells adhere to a thin basement membrane that is produced by both
      epithelial cells and the underlying stromal cells. Signals passing between
      epithelial cells and stromal cells are needed for normal gut structure. In gut
      diseases, however, epithelial cells and stromal cells produce large amounts of
      matrix degrading enzymes (matrix metalloproteinases), the function of which is
      only beginning to be elucidated. Here, we review the role of matrix
      metalloproteonases (MMPs) in the gut in health, in gut inflammation, and in
      cancer.

PMID- 18073416
TI  - The historical discovery of the nine species in the Drosophila melanogaster
      species subgroup.

PMID- 18073417
TI  - Large-scale survey of cytosine methylation of retrotransposons and the impact of
      readout transcription from long terminal repeats on expression of adjacent rice
      genes.
AB  - Transposable elements (TEs) represent approximately 45% of the human genome and
      50-90% of some grass genomes. While most elements contain inactivating mutations,
      others are reversibly inactivated (silenced) by epigenetic mechanisms, including
      cytosine methylation. Previous studies have shown that retrotransposons can
      influence the expression of adjacent host genes. In this study, the methylation
      patterns of TEs and their flanking sequences in different tissues were undertaken
      using a novel technique called transposon methylation display (TMD). TMD was
      successfully applied on a highly copied (approximately 1000 copies), newly
      amplified LTR retrotransposon family in rice called Dasheng. We determined that
      the methylation status of a subset of LTRs varies in leaves vs. roots. In
      addition, we determined that tissue-specific LTR methylation correlated with
      tissue-specific expression of the flanking rice gene. Genes showing tissue
      specific expression were in opposite orientation relative to the LTR. Antisense
      transcripts were detected in the tissue where the sense transcripts from that
      gene were not detected. Comparative analysis of Dasheng LTR methylation in the
      two subspecies, japonica vs. indica revealed LTR-mediated differences in
      subspecies gene expression. Subspecies-specific expression was due either to
      polymorphic Dasheng insertion sites between the two subspecies or to subspecies
      specific methylation of LTRs at the same locus accounted for observed differences
      in the expression of adjacent genes.

PMID- 18073418
TI  - Extensive allelic variation in gene expression in populus F1 hybrids.
AB  - Hybridization between plant species can induce speciation as well as phenotypic
      novelty and heterosis. Hybrids also can show genome rearrangements and gene
      expression changes compared with their parents. Here we determined the allelic
      variation in gene expression in Populus trichocarpa x Populus deltoides F(1)
      hybrids. Among 30 genes analyzed in four independently formed hybrids, 17 showed
      >1.5-fold expression biases for one of the two alleles, and there was monoallelic
      expression of one gene. Expression ratios of the alleles differed between leaves
      and stems for 10 genes. The results suggest differential regulation of the two
      parental alleles in the hybrids. To determine if the allelic expression biases
      were caused by hybridization we compared the ratios of species-specific
      transcripts between an F(1) hybrid and its parents. Thirteen of 19 genes showed
      allelic expression ratios in the hybrid that were significantly different from
      the ratios of the parental species. The P. deltoides allele of one gene was
      silenced in the hybrid. Modes of gene regulation were inferred from the hybrid
      parent comparisons. Cis-regulation was inferred for 6 genes, trans-regulation for
      1 gene, and combined cis- and trans-regulation for 9 genes. The results from this
      study indicate that hybridization between plant species can have extensive
      effects on allelic expression patterns, some of which might lead to phenotypic
      changes.

PMID- 18073419
TI  - Two zinc-cluster transcription factors control induction of alternative oxidase
      in Neurospora crassa.
AB  - The alternative oxidase transfers electrons from ubiquinol to molecular oxygen,
      providing a mechanism for bypassing the later steps of the standard cytochrome
      mediated electron transport chain. The enzyme is found in an array of organisms
      and in many cases is known to be produced in response to perturbations of the
      standard chain. Alternative oxidase is encoded in the nucleus but functions in
      the inner mitochondrial membrane. This implies the existence of a retrograde
      regulation pathway for communicating from the mitochondrion to the nucleus to
      induce alternative oxidase expression. Previous studies on alternative oxidase in
      fungi and plants have shown that a number of genes are required for expression of
      the enzyme, but the identity of these genes has remained elusive. By gene rescue
      we have now shown that the aod-2 and aod-5 genes of Neurospora crassa encode
      transcription factors of the zinc-cluster family. Electrophoretic mobility shift
      assays show that the DNA-binding domains of the AOD2 and AOD5 proteins act in
      tandem to bind a sequence element in the alternative oxidase gene promoter that
      is required for expression. Both proteins contain potential PAS domains near
      their C terminus, which are found primarily in proteins involved in signal
      transduction.

PMID- 18073420
TI  - Characterization of new Spt3 and TATA-binding protein mutants of Saccharomyces
      cerevisiae: Spt3 TBP allele-specific interactions and bypass of Spt8.
AB  - The Spt-Ada-Gcn5-acetyltransferase (SAGA) complex of Saccharomyces cerevisiae is
      a multifunctional coactivator complex that has been shown to regulate
      transcription by distinct mechanisms. Previous results have shown that the Spt3
      and Spt8 components of SAGA regulate initiation of transcription of particular
      genes by controlling the level of TATA-binding protein (TBP/Spt15) associated
      with the TATA box. While biochemical evidence exists for direct Spt8-TBP
      interactions, similar evidence for Spt3-TBP interactions has been lacking. To
      learn more about Spt3-TBP interactions in vivo, we have isolated a new class of
      spt3 mutations that cause a dominant-negative phenotype when overexpressed. These
      mutations all cluster within a conserved region of Spt3. The isolation of
      extragenic suppressors of one of these spt3 mutations has identified two new
      spt15 mutations that show allele-specific interactions with spt3 mutations with
      respect to transcription and the recruitment of TBP to particular promoters. In
      addition, these new spt15 mutations partially bypass an spt8 null mutation.
      Finally, we have examined the level of SAGA-TBP physical interaction in these
      mutants. While most spt3, spt8, and spt15 mutations do not alter SAGA-TBP
      interactions, one spt3 mutation, spt3-401, causes a greatly increased level of
      SAGA-TBP physical association. These results, taken together, suggest that a
      direct Spt3-TBP interaction is required for normal TBP levels at Spt3-dependent
      promoters in vivo.

PMID- 18073421
TI  - Differential nuclear localization does not determine the silencing status of
      Saccharomyces cerevisiae telomeres.
AB  - In Saccharomyces cerevisiae, genes near telomeres are transcriptionally
      repressed, a phenomenon termed telomere position effect (TPE). Yeast telomeres
      cluster near the nuclear periphery, as do foci of proteins essential for TPE:
      Rap1p, Sir2-4p, and yKu70p/yKu80p. However, it is not clear if localization of
      telomeres to the periphery actually contributes to TPE. We examined the
      localization patterns of two telomeres with different levels of TPE: truncated
      VII-L and native VI-R. For both telomeres, localization to the nuclear periphery
      or to the silencing foci was neither necessary nor sufficient for TPE. Moreover,
      there was no correlation between TPE levels and the extent of localization.
      Tethering the truncated VII-L telomere to the nuclear periphery resulted in a
      modest increase in TPE. However, tethering did not bypass the roles of yKu70p,
      Sir4p, or Esc1p in TPE. Using mutations in RIF genes that bypass the role of Ku
      in TPE, a correlation between the level of silencing and the number of Rap1p foci
      present in the nucleus was observed, suggesting that Sir protein levels at
      telomeres determine both the level of TPE and the number of foci.

PMID- 18073422
TI  - Deletion-mutant mtDNA increases in somatic tissues but decreases in female germ
      cells with age.
AB  - The proportions of mutant and wild-type mtDNA are crucial in determining the
      severity of mitochondrial diseases. It has been generally considered that
      deletion-mutant mtDNA has replication advantages and accumulates with time. Here,
      we examine the tissue-by-tissue proportions of mutant mtDNA with a 4696-bp
      deletion (DeltamtDNA) and wild-type mtDNA in mitochondrial disease model mice
      (mito-mice). Comparison of the proportions of DeltamtDNA in each tissue at
      various ages showed that the rate of accumulation of DeltamtDNA differed among
      tissues. The heart, skeletal muscles, kidney, liver, testis, and ovary showed
      increases in the proportion of DeltamtDNA with age, but the pancreas, spleen,
      brain, and blood showed only a slight or no increase in proportion. In contrast
      to the somatic tissues, however, the germ cells of female mito-mice and resultant
      offspring showed a strong decrease in DeltamtDNA with maternal age. The decrease
      was so acute that some offspring showed complete disappearance of DeltamtDNA,
      even though their elder brothers and sisters had high proportions of DeltamtDNA.
      Female germ cells have a machinery that prevents the inheritance of defective
      mtDNA to the following generation since germ cells are kept for a long time until
      they are ovulated.

PMID- 18073423
TI  - Multiple functions and dynamic activation of MPK-1 extracellular signal-regulated
      kinase signaling in Caenorhabditis elegans germline development.
AB  - The raison d'etre of the germline is to produce oocytes and sperm that pass
      genetic material and cytoplasmic constituents to the next generation. To achieve
      this goal, many developmental processes must be executed and coordinated. ERK,
      the terminal MAP kinase of a number of signaling pathways, controls many aspects
      of development. Here we present a comprehensive analysis of MPK-1 ERK in
      Caenorhabditis elegans germline development. MPK-1 functions in four
      developmental switches: progression through pachytene, oocyte meiotic
      maturation/ovulation, male germ cell fate specification, and a nonessential
      function of promoting the proliferative fate. MPK-1 also regulates multiple
      aspects of cell biology during oogenesis, including membrane organization and
      morphogenesis: organization of pachytene cells on the surface of the gonadal
      tube, oocyte organization and differentiation, oocyte growth control, and oocyte
      nuclear migration. MPK-1 activation is temporally/spatially dynamic and most
      processes appear to be controlled through sustained activation. MPK-1 thus may
      act not only in the control of individual processes but also in the coordination
      of contemporaneous processes and the integration of sequential processes.
      Knowledge of the dynamic activation and diverse functions of MPK-1 provides the
      foundation for identification of upstream signaling cascades responsible for
      region-specific activation and the downstream substrates that mediate the various
      processes.

PMID- 18073424
TI  - A Measurable increase in oxidative damage due to reduction in superoxide
      detoxification fails to shorten the life span of long-lived mitochondrial mutants
      of Caenorhabditis elegans.
AB  - SOD-1 and SOD-2 detoxify superoxide in the cytoplasm and mitochondria. We find
      that, although several long-lived mutants of Caenorhabditis elegans have
      increased SOD levels, this phenomenon does not correlate with life span or growth
      rate. Furthermore, although disruption of sod-1 or -2 expression produces
      numerous phenotypes, including increased sensitivity to paraquat and increased
      oxidative damage to proteins (except in daf-2 mutants), this fails to shorten the
      life span of these long-lived mutants. In fact, sod-1(RNAi) increases the life
      span of daf-2 mutants and sod-2(RNAi) that of clk-1 mutants. Our results suggest
      that increased superoxide detoxification and low oxidative damage are not crucial
      for the longevity of the mutants examined, with the possible exception of daf-2,
      where our results are inconclusive. These results are surprising because several
      of the long-lived mutants that we examined specifically affect mitochondrial
      electron transport, a process whose involvement in life-span determination is
      believed to be related to superoxide generation. We discuss the significance of
      our findings in light of the oxidative stress theory of aging.

PMID- 18073425
TI  - Genomewide spatial correspondence between nonsynonymous divergence and neutral
      polymorphism reveals extensive adaptation in Drosophila.
AB  - The effect of recurrent selective sweeps is a spatially heterogeneous reduction
      in neutral polymorphism throughout the genome. The pattern of reduction depends
      on the selective advantage and recurrence rate of the sweeps. Because many
      adaptive substitutions responsible for these sweeps also contribute to
      nonsynonymous divergence, the spatial distribution of nonsynonymous divergence
      also reflects the distribution of adaptive substitutions. Thus, the spatial
      correspondence between neutral polymorphism and nonsynonymous divergence may be
      especially informative about the process of adaptation. Here we study this
      correspondence using genomewide polymorphism data from Drosophila simulans and
      the divergence between D. simulans and D. melanogaster. Focusing on highly
      recombining portions of the autosomes, at a spatial scale appropriate to the
      study of selective sweeps, we find that neutral polymorphism is both lower and,
      as measured by a new statistic Q(S), less homogeneous where nonsynonymous
      divergence is higher and that the spatial structure of this correlation is best
      explained by the action of strong recurrent selective sweeps. We introduce a
      method to infer, from the spatial correspondence between polymorphism and
      divergence, the rate and selective strength of adaptation. Our results
      independently confirm a high rate of adaptive substitution (approximately 1/3000
      generations) and newly suggest that many adaptations are of surprisingly great
      selective effect (approximately 1%), reducing the effective population size by
      approximately 15% even in highly recombining regions of the genome.

PMID- 18073427
TI  - Inferring human population sizes, divergence times and rates of gene flow from
      mitochondrial, X and Y chromosome resequencing data.
AB  - We estimate parameters of a general isolation-with-migration model using
      resequence data from mitochondrial DNA (mtDNA), the Y chromosome, and two loci on
      the X chromosome in samples of 25-50 individuals from each of 10 human
      populations. Application of a coalescent-based Markov chain Monte Carlo technique
      allows simultaneous inference of divergence times, rates of gene flow, as well as
      changes in effective population size. Results from comparisons between sub
      Saharan African and Eurasian populations estimate that 1500 individuals founded
      the ancestral Eurasian population approximately 40 thousand years ago (KYA).
      Furthermore, these small Eurasian founding populations appear to have grown much
      more dramatically than either African or Oceanian populations. Analyses of sub
      Saharan African populations provide little evidence for a history of population
      bottlenecks and suggest that they began diverging from one another upward of 50
      KYA. We surmise that ancestral African populations had already been
      geographically structured prior to the founding of ancestral Eurasian
      populations. African populations are shown to experience low levels of
      mitochondrial DNA gene flow, but high levels of Y chromosome gene flow. In
      particular, Y chromosome gene flow appears to be asymmetric, i.e., from the Bantu
      speaking population into other African populations. Conversely, mitochondrial
      gene flow is more extensive between non-African populations, but appears to be
      absent between European and Asian populations.

PMID- 18073428
TI  - The evolution of two mutations during clonal expansion.
AB  - Knudson's two-hit hypothesis proposes that two genetic changes in the RB1 gene
      are the rate-limiting steps of retinoblastoma. In the inherited form of this
      childhood eye cancer, only one mutation emerges during somatic cell divisions
      while in sporadic cases, both alleles of RB1 are inactivated in the growing
      retina. Sporadic retinoblastoma serves as an example of a situation in which two
      mutations are accumulated during clonal expansion of a cell population. Other
      examples include evolution of resistance against anticancer combination therapy
      and inactivation of both alleles of a metastasis-suppressor gene during tumor
      growth. In this article, we consider an exponentially growing population of cells
      that must evolve two mutations to (i) evade treatment, (ii) make a step toward
      (invasive) cancer, or (iii) display a disease phenotype. We calculate the
      probability that the population has evolved both mutations before it reaches a
      certain size. This probability depends on the rates at which the two mutations
      arise; the growth and death rates of cells carrying none, one, or both mutations;
      and the size the cell population reaches. Further, we develop a formula for the
      expected number of cells carrying both mutations when the final population size
      is reached. Our theory establishes an understanding of the dynamics of two
      mutations during clonal expansion.

PMID- 18073429
TI  - Diversification rates increase with population size and resource concentration in
      an unstructured habitat.
AB  - Understanding the mechanisms controlling the generation and maintenance of
      biodiversity provides some of the planet's greatest and most pressing challenges.
      Variation in resource concentration, which varies widely at multiple scales, may
      cause biodiversity to increase, decrease, or exhibit a unimodal response and
      underlying mechanisms remain obscure. We established experimental cultures of
      long-term stationary phase (LTSP) Escherichia coli to test whether per capita
      heterozygosity varies with resource concentration, and, if so, whether population
      sizes associated with different resource concentrations contributed to these
      patterns. Our results provide the clearest example to date of increasing per
      capita heterozygosity with increasing resource concentration. Further, our
      experimental manipulations of population size, independent of resource
      concentration, provide the first unequivocal evidence that population size is one
      of the underlying factors controlling per capita heterozygosity along such
      resource gradients. Specifically, we show that cultures with higher maximum
      population sizes, associated with higher resource concentrations, have higher per
      capita heterozygosity. These experiments provide the first experimental evidence
      for an underappreciated factor controlling biodiversity along resource gradients-
      population size. This direct evidence of population size influencing
      diversification rates has implications for regional and global scale patterns of
      biodiversity.

PMID- 18073426
TI  - Investigation of the demographic and selective forces shaping the nucleotide
      diversity of genes involved in nod factor signaling in Medicago truncatula.
AB  - Symbiotic nitrogen-fixing rhizobia are able to trigger root deformation in their
      Fabaceae host plants, allowing their intracellular accommodation. They do so by
      delivering molecules called Nod factors. We analyzed the patterns of nucleotide
      polymorphism of five genes controlling early Nod factor perception and signaling
      in the Fabaceae Medicago truncatula to understand the selective forces shaping
      the evolution of these genes. We used 30 M. truncatula genotypes sampled in a
      genetically homogeneous region of the species distribution range. We first
      sequenced 24 independent loci and detected a genomewide departure from the
      hypothesis of neutrality and demographic equilibrium that suggests a population
      expansion. These data were used to estimate parameters of a simple demographic
      model incorporating population expansion. The selective neutrality of genes
      controlling Nod factor perception was then examined using a combination of two
      complementary neutrality tests, Tajima's D and Fay and Wu's standardized H. The
      joint distribution of D and H expected under neutrality was obtained under the
      fitted population expansion model. Only the gene DMI1, which is expected to
      regulate the downstream signal, shows a pattern consistent with a putative
      selective event. In contrast, the receptor-encoding genes NFP and NORK show no
      significant signatures of selection. Among the genes that we analyzed, only DMI1
      should be viewed as a candidate for adaptation in the recent history of M.
      truncatula.

PMID- 18073430
TI  - Joint inference of the distribution of fitness effects of deleterious mutations
      and population demography based on nucleotide polymorphism frequencies.
AB  - The distribution of fitness effects of new mutations (DFE) is important for
      addressing several questions in genetics, including the nature of quantitative
      variation and the evolutionary fate of small populations. Properties of the DFE
      can be inferred by comparing the distributions of the frequencies of segregating
      nucleotide polymorphisms at selected and neutral sites in a population sample,
      but demographic changes alter the spectrum of allele frequencies at both neutral
      and selected sites, so can bias estimates of the DFE if not accounted for. We
      have developed a maximum-likelihood approach, based on the expected allele
      frequency distribution generated by transition matrix methods, to estimate
      parameters of the DFE while simultaneously estimating parameters of a demographic
      model that allows a population size change at some time in the past. We tested
      the method using simulations and found that it accurately recovers simulated
      parameter values, even if the simulated demography differs substantially from
      that assumed in our analysis. We use our method to estimate parameters of the DFE
      for amino acid-changing mutations in humans and Drosophila melanogaster. For a
      model of unconditionally deleterious mutations, with effects sampled from a gamma
      distribution, the mean estimate for the distribution shape parameter is
      approximately 0.2 for human populations, which implies that the DFE is strongly
      leptokurtic. For Drosophila populations, we estimate that the shape parameter is
      approximately 0.35. Differences in the shape of the distribution and the mean
      selection coefficient between humans and Drosophila result in significantly more
      strongly deleterious mutations in Drosophila than in humans, and, conversely,
      nearly neutral mutations are significantly less frequent.

PMID- 18073433
TI  - The reacquisition of biotin prototrophy in Saccharomyces cerevisiae involved
      horizontal gene transfer, gene duplication and gene clustering.
AB  - The synthesis of biotin, a vitamin required for many carboxylation reactions, is
      a variable trait in Saccharomyces cerevisiae. Many S. cerevisiae strains,
      including common laboratory strains, contain only a partial biotin synthesis
      pathway. We here report the identification of the first step necessary for the
      biotin synthesis pathway in S. cerevisiae. The biotin auxotroph strain S288c was
      able to grow on media lacking biotin when BIO1 and the known biotin synthesis
      gene BIO6 were introduced together on a plasmid vector. BIO1 is a paralog of
      YJR154W, a gene of unknown function and adjacent to BIO6. The nature of BIO1
      illuminates the remarkable evolutionary history of the biotin biosynthesis
      pathway in S. cerevisiae. This pathway appears to have been lost in an ancestor
      of S. cerevisiae and subsequently rebuilt by a combination of horizontal gene
      transfer and gene duplication followed by neofunctionalization. Unusually, for S.
      cerevisiae, most of the genes required for biotin synthesis in S. cerevisiae are
      grouped in two subtelomeric gene clusters. The BIO1-BIO6 functional cluster is an
      example of a cluster of genes of "dispensable function," one of the few
      categories of genes in S. cerevisiae that are positionally clustered.

PMID- 18073432
TI  - Nucleotide variation in wild and inbred mice.
AB  - The house mouse is a well-established model organism, particularly for studying
      the genetics of complex traits. However, most studies of mice use classical
      inbred strains, whose genomes derive from multiple species. Relatively little is
      known about the distribution of genetic variation among these species or how
      variation among strains relates to variation in the wild. We sequenced intronic
      regions of five X-linked loci in large samples of wild Mus domesticus and M.
      musculus, and we found low levels of nucleotide diversity in both species. We
      compared these data to published data from short portions of six X-linked and 18
      autosomal loci in wild mice. We estimate that M. domesticus and M. musculus
      diverged <500,000 years ago. Consistent with this recent divergence, some gene
      genealogies were reciprocally monophyletic between these species, while others
      were paraphyletic or polyphyletic. In general, the X chromosome was more
      differentiated than the autosomes. We resequenced classical inbred strains for
      all 29 loci and found that inbred strains contain only a small amount of the
      genetic variation seen in wild mice. Notably, the X chromosome contains
      proportionately less variation among inbred strains than do the autosomes.
      Moreover, variation among inbred strains derives from differences between species
      as well as from differences within species, and these proportions differ in
      different genomic regions. Wild mice thus provide a reservoir of additional
      genetic variation that may be useful for mapping studies. Together these results
      suggest that wild mice will be a valuable complement to laboratory strains for
      studying the genetics of complex traits.

PMID- 18073434
TI  - Mapping quantitative trait loci from a single-tail sample of the phenotype
      distribution including survival data.
AB  - A new effective Bayesian quantitative trait locus (QTL) mapping approach for the
      analysis of single-tail selected samples of the phenotype distribution is
      presented. The approach extends the affected-only tests to single-tail sampling
      with quantitative traits such as the log-normal survival time or
      censored/selected traits. A great benefit of the approach is that it enables the
      utilization of multiple-QTL models, is easy to incorporate into different data
      designs (experimental and outbred populations), and can potentially be extended
      to epistatic models. In inbred lines, the method exploits the fact that the
      parental mating type and the linkage phases (haplotypes) are known by definition.
      In outbred populations, two-generation data are needed, for example, selected
      offspring and one of the parents (the sires) in breeding material. The idea is to
      statistically (computationally) generate a fully complementary, maximally
      dissimilar, observation for each offspring in the sample. Bayesian data
      augmentation is then used to sample the space of possible trait values for the
      pseudoobservations. The benefits of the approach are illustrated using simulated
      data sets and a real data set on the survival of F(2) mice following infection
      with Listeria monocytogenes.

PMID- 18073431
TI  - Gene-based sequence diversity analysis of field pea (Pisum).
AB  - Sequence diversity of 39 dispersed gene loci was analyzed in 48 diverse
      individuals representative of the genus Pisum. The different genes show large
      variation in diversity parameters, suggesting widely differing levels of
      selection and a high overall diversity level for the species. The data set yields
      a genetic diversity tree whose deep branches, involving wild samples, are
      preserved in a tree derived from a polymorphic retrotransposon insertions in an
      identical sample set. Thus, gene regions and intergenic "junk DNA" share a
      consistent picture for the genomic diversity of Pisum, despite low linkage
      disequilibrium in wild and landrace germplasm, which might be expected to allow
      independent evolution of these very different DNA classes. Additional lines of
      evidence indicate that recombination has shuffled gene haplotypes efficiently
      within Pisum, despite its high level of inbreeding and widespread geographic
      distribution. Trees derived from individual gene loci show marked differences
      from each other, and genetic distance values between sample pairs show high
      standard deviations. Sequence mosaic analysis of aligned sequences identifies
      nine loci showing evidence for intragenic recombination. Lastly, phylogenetic
      network analysis confirms the non-treelike structure of Pisum diversity and
      indicates the major germplasm classes involved. Overall, these data emphasize the
      artificiality of simple tree structures for representing genomic sequence
      variation within Pisum and emphasize the need for fine structure haplotype
      analysis to accurately define the genetic structure of the species.

PMID- 18073435
TI  - Genetic analysis of craniofacial traits in the medaka.
AB  - Family and twin studies suggest that a substantial genetic component underlies
      individual differences in craniofacial morphology. In the current study, we
      quantified 444 craniofacial traits in 100 individuals from two inbred medaka
      (Oryzias latipes) strains, HNI and Hd-rR. Relative distances between defined
      landmarks were measured in digital images of the medaka head region. A total of
      379 traits differed significantly between the two strains, indicating that many
      craniofacial traits are controlled by genetic factors. Of these, 89 traits were
      analyzed via interval mapping of 184 F(2) progeny from an intercross between HNI
      and Hd-rR. We identified quantitative trait loci for 66 craniofacial traits. The
      highest logarithm of the odds score was 6.2 for linkage group (LG) 9 and 11.
      Trait L33, which corresponds to the ratio of head length to head height at eye
      level, mapped to LG9; trait V15, which corresponds to the ratio of snout length
      to head width measured behind the eyes, mapped to LG11. Our initial results
      confirm the potential of the medaka as a model system for the genetic analysis of
      complex traits such as craniofacial morphology.

PMID- 18073436
TI  - The impact of genetic relationship information on genome-assisted breeding
      values.
AB  - The success of genomic selection depends on the potential to predict genome
      assisted breeding values (GEBVs) with high accuracy over several generations
      without additional phenotyping after estimating marker effects. Results from both
      simulations and practical applications have to be evaluated for this potential,
      which requires linkage disequilibrium (LD) between markers and QTL. This study
      shows that markers can capture genetic relationships among genotyped animals,
      thereby affecting accuracies of GEBVs. Strategies to validate the accuracy of
      GEBVs due to LD are given. Simulations were used to show that accuracies of GEBVs
      obtained by fixed regression-least squares (FR-LS), random regression-best linear
      unbiased prediction (RR-BLUP), and Bayes-B are nonzero even without LD. When LD
      was present, accuracies decrease rapidly in generations after estimation due to
      the decay of genetic relationships. However, there is a persistent accuracy due
      to LD, which can be estimated by modeling the decay of genetic relationships and
      the decay of LD. The impact of genetic relationships was greatest for RR-BLUP.
      The accuracy of GEBVs can result entirely from genetic relationships captured by
      markers, and to validate the potential of genomic selection, several generations
      have to be analyzed to estimate the accuracy due to LD. The method of choice was
      Bayes-B; FR-LS should be investigated further, whereas RR-BLUP cannot be
      recommended.

PMID- 18073437
TI  - Quantifying evidence for candidate gene polymorphisms: Bayesian analysis
      combining sequence-specific and quantitative trait loci colocation information.
AB  - We calculate posterior probabilities for candidate genes as a function of genomic
      location. Posterior probabilities for quantitative trait loci (QTL) presence in a
      small interval are calculated using a Bayesian model-selection approach based on
      the Bayesian information criterion (BIC) and used to combine QTL colocation
      information with sequence-specific evidence, e.g., from differential expression
      and/or association studies. Our method takes into account uncertainty in
      estimation of number and locations of QTL and estimated map position. Posterior
      probabilities for QTL presence were calculated for simulated data with n = 100,
      300, and 1200 QTL progeny and compared with interval mapping and composite
      interval mapping. Candidate genes that mapped to QTL regions had substantially
      larger posterior probabilities. Among candidates with a given Bayes factor, those
      that map near a QTL are more promising for further investigation with association
      studies and functional testing or for use in marker-aided selection. The BIC is
      shown to correspond very closely to Bayes factors for linear models with a nearly
      noninformative Zellner prior for the simulated QTL data with n > or = 100. It is
      shown how to modify the BIC to use a subjective prior for the QTL effects.

PMID- 18073438
TI  - Mapping quantitative trait loci affecting susceptibility to Marek's disease virus
      in a backcross population of layer chickens.
AB  - Marek's disease (MD), caused by the oncogenic MD avian herpes virus (MDV), is a
      major source of economic losses to the poultry industry. A reciprocal backcross
      (BC) population (total 2052 individuals) was generated by crossing two partially
      inbred commercial Leghorn layer lines known to differ in MDV resistance, measured
      as survival time after challenge with a (vv+) MDV. QTL affecting resistance were
      identified by selective DNA pooling using a panel of 198 microsatellite markers
      covering two-thirds of the chicken genome. Data for each BC were analyzed
      separately, and as a combined data set. Markers showing significant association
      with resistance generally appeared in blocks of two or three, separated by blocks
      of nonsignificant markers. Defined this way, 15 chromosomal regions (QTLR)
      affecting MDV resistance, distributed among 10 chromosomes (GGA 1, 2, 3, 4, 5, 7,
      8, 9, 15, and Z), were identified. The identified QTLR include one gene and three
      QTL associated with resistance in previous studies of other lines, and three
      additional QTL associated with resistance in previous studies of the present
      lines. These QTL could be used in marker-assisted selection (MAS) programs for
      MDV resistance and as a platform for high-resolution mapping and positional
      cloning of the resistance genes.

PMID- 18073439
TI  - Flowering time quantitative trait Loci analysis of oilseed brassica in multiple
      environments and genomewide alignment with Arabidopsis.
AB  - Most agronomical traits exhibit quantitative variation, which is controlled by
      multiple genes and are environmentally dependent. To study the genetic variation
      of flowering time in Brassica napus, a DH population and its derived
      reconstructed F(2) population were planted in 11 field environments. The
      flowering time varied greatly with environments; 60% of the phenotypic variation
      was attributed to genetic effects. Five to 18 QTL at a statistically significant
      level (SL-QTL) were detected in each environment and, on average, two new SL-QTL
      were discovered with each added environment. Another type of QTL, micro-real QTL
      (MR-QTL), was detected repeatedly from at least 2 of the 11 environments;
      resulting in a total of 36 SL-QTL and 6 MR-QTL. Sixty-three interacting pairs of
      loci were found; 50% of them were involved in QTL. Hundreds of floral transition
      genes in Arabidopsis were aligned with the linkage map of B. napus by in silico
      mapping; 28% of them aligned with QTL regions and 9% were consistent with
      interacting loci. One locus, BnFLC10, in N10 and a QTL cluster in N16 were
      specific to spring- and winter-cropped environments respectively. The number of
      QTL, interacting loci, and aligned functional genes revealed a complex genetic
      network controlling flowering time in B. napus.

PMID- 18073440
TI  - A microsatellite genetic map of the turbot (Scophthalmus maximus).
AB  - A consensus microsatellite-based linkage map of the turbot (Scophthalmus maximus)
      was constructed from two unrelated families. The mapping panel was derived from a
      gynogenetic family of 96 haploid embryos and a biparental diploid family of 85
      full-sib progeny with known linkage phase. A total of 242 microsatellites were
      mapped in 26 linkage groups, six markers remaining unlinked. The consensus map
      length was 1343.2 cM, with an average distance between markers of 6.5 +/- 0.5 cM.
      Similar length of female and male maps was evidenced. However, the mean
      recombination at common intervals throughout the genome revealed significant
      differences between sexes, approximately 1.6 times higher in the female than in
      the male. The comparison of turbot microsatellite flanking sequences against the
      Tetraodon nigroviridis genome revealed 55 significant matches, with a mean length
      of 102 bp and high sequence similarity (81-100%). The comparative mapping
      revealed significant syntenic regions among fish species. This study represents
      the first linkage map in the turbot, one of the most important flatfish in
      European aquaculture. This map will be suitable for QTL identification of
      productive traits in this species and for further evolutionary studies in fish
      and vertebrate species.

PMID- 18073441
TI  - Zinc regulates the stability of repetitive minisatellite DNA tracts during
      stationary phase.
AB  - Repetitive minisatellite DNA tracts are stable in mitotic cells but unstable in
      meiosis, altering in repeat number and repeat composition. As relatively little
      is known about the factors that influence minisatellite stability, we isolated
      mutations that destabilize a minisatellite repeat tract in the ADE2 gene of
      Saccharomyces cerevisiae. One mutant class exhibited a novel color segregation
      phenotype, "blebbing," characterized by minisatellite instability during
      stationary phase. Minisatellite tract alterations in blebbing strains consist
      exclusively of the loss of one 20-bp repeat. Timing experiments suggest that
      these tract alterations occur only after cells have entered stationary phase. Two
      complementation groups identified in this screen have mutations in either the
      high-affinity zinc transporter ZRT1 or its zinc-dependent transcriptional
      regulator ZAP1. The Deltazrt1 mutant specifically affects the stability of
      minisatellite tracts; microsatellites or simple insertions in the ADE2 reading
      frame are not destabilized by loss of ZRT1. The Deltazrt1 blebbing phenotype is
      partially dependent on a functional RAD50. Zinc is known for its role as an
      essential cofactor in many DNA-binding proteins. We describe possible models by
      which zinc can influence minisatellite stability. Our findings directly implicate
      zinc homeostasis in the maintenance of genomic stability during stationary phase.

PMID- 18073442
TI  - Investigating the genetic circuitry of mastermind in Drosophila, a notch signal
      effector.
AB  - Notch signaling regulates multiple developmental processes and is implicated in
      various human diseases. Through use of the Notch transcriptional co-activator
      mastermind, we conducted a screen for Notch signal modifiers using the Exelixis
      collection of insertional mutations, which affects approximately 50% of the
      Drosophila genome, recovering 160 genes never before associated with Notch,
      extending the previous roster of genes that interact functionally with the Notch
      pathway and mastermind. As the molecular identity for most recovered genes is
      known, gene ontology (GO) analysis was applied, grouping genes according to
      functional classifications. We identify novel Notch-associated GO categories,
      uncover nodes of integration between Notch and other signaling pathways, and
      unveil groups of modifiers that suggest the existence of Notch-independent
      mastermind functions, including a conserved ability to regulate Wnt signaling.

PMID- 18073443
TI  - Genomic instability within centromeres of interspecific marsupial hybrids.
AB  - Several lines of evidence suggest that, within a lineage, particular genomic
      regions are subject to instability that can lead to specific types of chromosome
      rearrangements important in species incompatibility. Within family Macropodidae
      (kangaroos, wallabies, bettongs, and potoroos), which exhibit recent and
      extensive karyotypic evolution, rearrangements involve chiefly the centromere. We
      propose that centromeres are the primary target for destabilization in cases of
      genomic instability, such as interspecific hybridization, and participate in the
      formation of novel chromosome rearrangements. Here we use standard cytological
      staining, cross-species chromosome painting, DNA probe analyses, and scanning
      electron microscopy to examine four interspecific macropodid hybrids (Macropus
      rufogriseus x Macropus agilis). The parental complements share the same centric
      fusions relative to the presumed macropodid ancestral karyotype, but can be
      differentiated on the basis of heterochromatic content, M. rufogriseus having
      larger centromeres with large C-banding positive regions. All hybrids exhibited
      the same pattern of chromosomal instability and remodeling specifically within
      the centromeres derived from the maternal (M. rufogriseus) complement. This
      instability included amplification of a satellite repeat and a transposable
      element, changes in chromatin structure, and de novo whole-arm rearrangements. We
      discuss possible reasons and mechanisms for the centromeric instability and
      remodeling observed in all four macropodid hybrids.

PMID- 18073445
TI  - The tetrad-pollen model fails to explain the bias in Mendel's pea (Pisum sativum)
      experiments.
AB  - For >40 years, geneticists and science historians have appealed to the tetrad
      pollen model as an explanation of the bias toward expectation in Mendel's data,
      albeit without experimental support. Our experiments demonstrate that pollen
      sampling during self-pollination in pea conforms to the binomial distribution
      with no evidence of a tetrad-pollen effect.

PMID- 18073444
TI  - Synthetic lethal interactions identify phenotypic "interologs" of the spindle
      assembly checkpoint components.
AB  - Here, we report genetic interactions with mdf-1(gk2)/MAD1 in Caenorhabditis
      elegans. Nine are evolutionarily conserved or phenotypic "interologs" and two are
      novel enhancers, hcp-1 and bub-3. We show that HCP-1 and HCP-2, the two CENP-F
      related proteins, recently implicated in the spindle assembly checkpoint (SAC)
      function, do not have identical functions, since hcp-1(RNAi), but not hcp
      2(RNAi), enhances the lethality of the SAC mutants.

PMID- 18073446
TI  - The role of double-stranded break repair in the creation of phenotypic diversity
      at cereal VRN1 loci.
AB  - Nonhomologous repair of double-stranded breaks, although fundamental to the
      maintenance of genomic integrity in all eukaryotes, has received little attention
      as to its evolutionary consequences in the generation and selection of phenotypic
      diversity. Here we document the role of illegitimate recombination in the
      creation of novel alleles in VRN1 orthologs selected to confer adaptation to
      annual cropping systems in barley and wheat.

PMID- 18073447
TI  - Subtelomeric elements influence but do not determine silencing levels at
      Saccharomyces cerevisiae telomeres.
AB  - In Saccharomyces cerevisiae, genes placed near telomeres are transcriptionally
      repressed (telomere position effect, TPE). Although telomeric DNA sequence is the
      same at all chromosome ends, the subtelomeric elements (STEs) and level of TPE
      vary from telomere to telomere. We tested whether STEs determine TPE levels. STEs
      contributed to TPE, as deleting the X element from the VI-R telomere modestly
      decreased silencing at this telomere. However, STEs were not the major
      determinant of TPE levels, as inserting the VI-R X element at the truncated VII-L
      telomere did not increase TPE. These data suggest that the TPE levels of
      individual telomeres are dependent on some aspect of chromosome context.

PMID- 18073448
TI  - Cell cycle arrest of stamen initials in maize sex determination.
AB  - The maize sex determination pathway results in the arrest of stamen in ear
      spikelets and the abortion of pistils in both the tassel spikelets and in the
      secondary florets of ear spikelets. Arrested stamen cells showed no signs of DNA
      fragmentation, an absence of CYCLIN B expression, and an accumulation of the
      negative cell cycle regulator WEE1 RNA.

PMID- 18073449
TI  - Sustaining HIV prevention: HIV testing in health care settings.
AB  - The Centers for Disease Control and Prevention (CDC) recently issued revised HIV
      testing recommendations, including a recommendation for routine, voluntary
      screening for all persons aged 13 years to 64 years in health care settings.
      Screening is not based on risk, and prevention counseling in conjunction with HIV
      testing in health care settings is not required. The revisions were motivated in
      part by concerns regarding the substantial undiagnosed fraction of prevalent HIV
      infections in the United States and evidence awareness of HIV infection leads to
      substantial reductions in high-risk sexual behavior. It is hoped that
      implementation of these recommendations, which will require coordination and
      education initiatives, will increase identification of the large number of HIV
      infected individuals unaware of their infection status and facilitate their
      linkage to care. This article summarizes a presentation on HIV prevention and HIV
      testing in health care settings made by Kevin A. Fenton, MD, PhD, at the 10th
      Annual Ryan White HIV/AIDS Program Clinical Update in June 2007 in Phoenix, AZ.

PMID- 18073450
TI  - HIV resistance: frequency, testing, mechanisms.
AB  - Recent data suggest that the prevalence of drug-resistant HIV in newly diagnosed
      patients may have leveled off at approximately 10% over the past several years.
      Further, there is some indication that the rates of emergence of resistance
      during long-term treatment have decreased in recent years with optimization of
      antiretroviral therapy. The importance of initial resistance testing is
      emphasized by findings indicating markedly increased risk of treatment failure in
      patients with resistance mutations at baseline. Genotypic and phenotypic testing
      are each associated with advantages and disadvantages in initial and subsequent
      resistance testing. Data on resistance patterns for new drugs and new drug
      classes are beginning to emerge. This article summarizes a presentation on HIV
      resistance made by Daniel R. Kuritzkes, MD, at an International AIDS Society-USA
      Continuing Medical Education course in San Francisco in May 2007.

PMID- 18073451
TI  - Cardiovascular risk and risk management in HIV-infected patients.
AB  - Patients with HIV infection are at risk of cardiovascular disease from the same
      factors posing risk in the general population--eg, smoking, dyslipidemia,
      hypertension, obesity, and diabetes. HIV infection itself and antiretroviral
      therapy pose additional risk, but available data indicate that the relative rate
      of myocardial infarction is low and declining in the HIV-infected population.
      Cardiovascular risk should be addressed before initiation of antiretroviral
      therapy and frequently during follow-up, and decisions to alter therapy on the
      basis of adverse changes in metabolic risk factors should be made on an
      individual basis. Virologic control is the primary goal for HIV-infected persons
      with cardiovascular risk, and is the primary consideration in determining when to
      start antiretroviral therapy and when to change regimens. This article summarizes
      a presentation on cardiovascular risk and risk management in HIV-infected persons
      made by Oluwatoyin Adeyemi, MD, at an International AIDS Society-USA Continuing
      Medical Education course in Chicago in May 2007.

PMID- 18073452
TI  - Diagnosis and management of hepatitis B virus and HIV coinfection.
AB  - HIV and hepatitis B virus (HBV) coinfection increases HIV and HBV replication,
      hepatitis flares, and risk of progression to chronic HBV infection, cirrhosis,
      and hepatocellular carcinoma. HIV and HBV coinfection decreases frequency of
      hepatitis Be antibody (anti-HBe) and hepatitis B surface antibody (anti-HBs)
      seroconversion, increases risk of antiretroviral therapy-related hepatotoxicity,
      and reduces efficacy of HBV therapy. All newly diagnosed HIV patients should be
      screened for hepatitis A, B, and C viruses and vaccinated if not immune to
      hepatitis A or B viruses. HBV serology often is atypical in coinfection.
      Diagnosis of HBV coinfection in HIV infection is made on the basis of hepatitis B
      surface antigen (HBsAg)-positive, hepatitis B core antibody (anti-HBc total)
      positive, anti-HBs-positive status. Alanine aminotransferase levels in coinfected
      patients often are not reliable markers of liver inflammation. HBV infection
      should always be treated if coinfected patients are receiving antiretroviral
      therapy, since immune reconstitution under antiretroviral therapy poses risk for
      immune-associated liver damage in these patients. This article summarizes a
      presentation on HIV and HBV coinfection made by Marion G. Peters, MD, at an
      International AIDS Society-USA Continuing Medical Education course in San
      Francisco in May 2007.

PMID- 18073453
TI  - Downregulation of angiopoietin-1 and Tie2 in chronic hypoxic pulmonary
      hypertension.
AB  - BACKGROUND: Angiopoietins, newly discovered vascular-specific growth factors, and
      vascular endothelial growth factors (VEGF) play distinct and complementary roles
      in angiogenesis and vascular maturation. However, the exact roles of angiogenic
      factors in the adult pulmonary vasculature remain unclear. OBJECTIVE: To
      elucidate possible roles of angiopoietins and VEGF in the development of hypoxic
      pulmonary hypertension (PH), changes in the expression of angiogenic factors were
      examined. METHODS: The cellular distribution and expression of angiopoietins and
      their receptor Tie2 and VEGF were investigated by RT-PCR, immunoblot, and
      immunohistochemical methods in rat lung under normal and hypoxic conditions.
      RESULTS: During the development of PH with vascular remodeling characterized by a
      decrease in vessel density of intrapulmonary arteries, protein expression of
      angiopoietin-1 (Ang-1), Tie2, and VEGF significantly decreased in the pulmonary
      arteries, and Tie2 receptor was inactivated in the lung. The expression of
      angiopoietin-3 (Ang-3), an endogenous antagonist of Ang-1, significantly
      increased in the intima under hypoxic conditions. CONCLUSIONS: Since both Ang
      1/Tie2 and VEGF promote angiogenesis and vascular survival, and play protective
      roles in the adaptation of microvascular changes during the onset of PH, the
      downregulation of both Ang-1/Tie2 and VEGF and upregulation of Ang-3 appear to be
      associated with vascular rarefaction and the development of hypoxic PH.

PMID- 18073454
TI  - Effect of serum leptin levels on hypercapnic ventilatory response in obstructive
      sleep apnea.
AB  - BACKGROUND: Leptin levels have been reported to be higher in patients with
      obstructive sleep apnea (OSA) than in control subjects with matching age and body
      mass index (BMI). Although animal studies have shown that leptin augments
      hypercapnic ventilatory response (HCVR), the effect of leptin on HCVR has not
      been clarified in OSA. OBJECTIVES: To investigate whether leptin could augment
      HCVR during wakefulness in patients with OSA. METHODS: Of 134 consecutive
      patients with OSA, 13 eucapnic and 16 hypercapnic patients with OSA, and 12
      control subjects matched for sex, age, and BMI were selected. Fasting serum
      leptin levels were collected, and HCVR during wakefulness assessed by the slope
      between minute ventilation and end-tidal PCO(2). RESULTS: There was a significant
      positive relationship between serum leptin levels and HCVR in the group including
      control subjects and eucapnic patients with OSA (r = 0.42, p < 0.05). Subgroup
      analyses suggest that serum leptin levels and HCVR were significantly higher in
      eucapnic patients with OSA than in control subjects. On the other hand,
      hypercapnic patients had lower HCVR than eucapnic patients (p < 0.05), whereas
      serum leptin levels were similar between the two OSA subgroups. CONCLUSION:
      Leptin levels and HCVR are correlated as long as the eucapnic condition is
      maintained. We speculate that a stimulating effect of leptin on HCVR may be
      masked by the hypoventilation state.

PMID- 18073455
TI  - Streptococcus pneumoniae adherence in rats under different degrees and durations
      of cigarette smoke.
AB  - BACKGROUND: Bacterial adherence to buccal epithelial cells in chronic smokers has
      been reported to increase in vitro. However, it is unclear whether such adherence
      increases in hosts without epithelial changes linked to chronic smoking.
      OBJECTIVE: This was an in vivo investigation of whether or not there was a change
      in the Streptococcus pneumoniae adherence to buccal epithelial cells of rats
      exposed to different periods and degrees of environmental cigarette smoke.
      METHOD: Eighteen rats were divided into acute and chronic exposure groups, each
      containing 9 rats. Both groups were further divided into 3 subgroups each, which
      were exposed to low or high levels of cigarette smoke, or none at all. After the
      administration of smoke, S. pneumoniae (ATCC 49619) was inoculated into the
      buccal mucosa. One hour later, buccal epithelial cell samples were taken and the
      number of bacteria adhering to 40 buccal epithelial cells was counted. Pre- and
      postinoculation values and the groups administered smoke and the control groups
      were then compared. RESULTS: A significant increase in gram-positive diplococci
      adherence was determined in all groups after S. pneumoniae inoculation. S.
      pneumoniae was observed to adhere to buccal epithelial cells in all the control
      group rats and in those in the groups exposed to cigarette smoke. Pneumococcal
      adherence in the chronic exposure subgroups increased approximately 4-fold with
      low smoke exposure (p < 0.004) and approximately 7-fold with high smoke exposure
      (p < 0.0005). CONCLUSION: S. pneumoniae adherence was significantly high in rats
      chronically exposed to a high level of cigarette smoke, but not in the acute
      exposure groups.

PMID- 18073456
TI  - Parenchymal and vascular interactions in the pathogenesis of nonspecific
      interstitial pneumonia in systemic sclerosis and idiopathic interstitial
      pneumonia.
AB  - BACKGROUND: Interstitial lung disease is a well-recognized prognostic factor in
      systemic sclerosis (SSc). As the prognosis in nonspecific interstitial pneumonia
      (NSIP) has been described to be better in collagen vascular disorders compared to
      the idiopathic forms, we hypothesize that the mechanisms of repair and remodeling
      are different between these 2 forms of the disease. OBJECTIVES: To compare the
      mechanisms of repair and remodeling between SSc-associated NSIP and the
      idiopathic form, its impact on pulmonary function tests and survival rates.
      METHODS: We analyzed 18 biopsies from patients with NSIP associated with SSc and
      22 with idiopathic NSIP and compared the epithelial and vascular densities as
      well as vascular activity. RESULTS: Epithelial cell density was lower in SSc-NSIP
      when compared with idiopathic NSIP (p < 0.0001). Type II pneumocytes and Clara
      cells were reduced in idiopathic NSIP (p = 0.02). A decrease in microvessel
      density was found in SSc-NSIP compared to idiopathic NSIP (p < 0.0001). The
      vascular activity measured by VCAM expression was higher in NSIP-SSc when
      compared to the idiopathic group (p < 0.0001). The DLCO/VA in SSc-NSIP was more
      compromised. A direct association between vascular density and DLCO/VA was found
      (p = 0.02). There was no difference in the survival rate between the 2 groups
      after a follow-up of 36 months. CONCLUSIONS: Alterations in the epithelium and
      vasculature seem to differ in the pathogenesis of SSc-NSIP when compared to the
      idiopathic form of the disease. Further studies may be required to assess the
      significance of these findings and explore if they can provide prognostic and/or
      treatment information.

PMID- 18073457
TI  - Photoperiod influences the central effects of ghrelin on food intake, GH and LH
      secretion in sheep.
AB  - Ghrelin is a circulating peptide, primarily secreted by the gut, that has
      reported actions within the hypothalamo-pituitary axis to stimulate food intake,
      inhibit GnRH/LH secretion and stimulate GH secretion in monogastric species.
      Here, we examine responses to centrally administered ghrelin in a seasonal
      ruminant. Estradiol-implanted castrated male sheep with indwelling
      intracerebroventricular (i.c.v.) cannulae were kept with unrestricted food for 16
      weeks in long day photoperiod (LD, 16 h light/day) then 16 weeks in short days
      (SD, 8 h light/day). In week 16 of each photoperiod they were given a control
      (saline) i.c.v. injection on day 1 and ghrelin i.c.v. injection on day 2. Mean
      circulating endogenous plasma ghrelin concentrations showed no diurnal pattern
      and were similar between the photoperiods. Central ghrelin injection increased
      voluntary food intake 2-fold in the first hour after administration in LD but not
      in SD, decreased LH pulse frequency and amplitude in SD but not in LD, and
      stimulated GH release in both photoperiods, although there was a 1.5-fold larger
      response in LD. Therefore, central injection of ghrelin to sheep acutely
      stimulated food intake in LD, suppressed reproductive neuroendocrine output in
      SD, and stimulated GH secretion irrespective of photoperiod, although more
      pronounced in LD. These data indicate that photoperiod can influence hypothalamic
      appetite and reproductive neuroendocrine responses to ghrelin in seasonal
      species.

PMID- 18073458
TI  - Modulation of network-driven, GABA-mediated giant depolarizing potentials by SDF
      1alpha in the developing hippocampus.
AB  - Chemokine stromal cell-derived factor-1 (SDF-1, or CXCL12) plays an important
      role in brain development and functioning. Whole-cell patch clamp recordings were
      conducted on CA3 neurons in hippocampal slices prepared from neonatal rats
      between postnatal days 2 and 6 to study the modulatory effects of SDF-1alpha on
      network-driven, gamma-aminobutyric-acid-mediated giant depolarizing potentials
      (GDPs), a hallmark of the developing hippocampus. We found that SDF-1alpha, the
      only natural ligand for chemokine CXC motif receptor 4 (CXCR4), decreased GDP
      firing without significant effects on neuronal passive membrane properties in
      neonatal hippocampal neurons. The SDF-1alpha-mediated decrease in GDP firing was
      blocked by T140, a CXCR4 receptor antagonist, suggesting that SDF-1alpha
      modulates GDP firing via CXCR4. We also showed that endogenous SDF-1 exerts a
      tonic inhibitory action on GDPs in the developing hippocampus. As SDF-1/CXCR4 are
      highly expressed in the developing brain and GDPs are involved in activity
      dependent synapse formation and functioning, the inhibitory action of SDF-1alpha
      on GDPs may reflect a potential mechanism for chemokine regulation of neural
      development in early neonatal life.

PMID- 18073459
TI  - Fibroblast growth factor receptor 2 plays an essential role in telencephalic
      progenitors.
AB  - We used loss-of-function analysis to determine the role of fibroblast growth
      factor receptor 2 (FGFR2) in telencephalic progenitors, and also to examine
      interactions between FGFR and Notch signaling. While the telencephalon of FGFR2
      mutants appears grossly normal, mutant telencephalic progenitors exhibit altered
      proliferative behavior in vivo and in vitro. Based upon our prior finding that
      Notch1 activation increased neurosphere frequency in FGF2, we tested whether this
      effect is mediated by FGFR1 or FGFR2. We found that Notch1 activation increased
      neurosphere frequency in cells mutant for either FGFR1 or FGFR2, but had no
      effect on the reduced size of neurospheres mutant for those receptors. Additional
      analyses revealed biochemical changes in the adult neocortex mutant for the IIIc
      isoform of FGFR2, and essential roles for FGFR2 in nasopharynx, eyelid, and
      cornea development.

PMID- 18073460
TI  - Unusual manifestations of myelofibrosis in a patient with congenital asplenia.

PMID- 18073461
TI  - Rationale for combination angiotensin receptor blocker and angiotensin-converting
      enzyme inhibitor treatment and end-organ protection in patients with chronic
      kidney disease.
AB  - Chronic kidney disease (CKD) is a major public health problem that has received
      increasing attention because of the high rate of associated cardiovascular
      morbidity and mortality. Mounting evidence indicates that angiotensin-converting
      enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), drugs that
      inhibit the renin-angiotensin-aldosterone system (RAAS) safely slow down
      progression of CKD. There is also growing evidence supporting combination
      treatment of nephropathies with an ACE inhibitor plus an ARB to more completely
      block the RAAS and provide greater renoprotection than either an ACE inhibitor
      based or ARB-based regimen. The National Kidney Foundation suggests that ACE
      inhibitors and ARBs may be used in combination to reduce proteinuria in patients
      with kidney disease; however, larger outcomes trials are needed.

PMID- 18073462
TI  - A high glycemic meal suppresses the postprandial leptin response in normal
      healthy adults.
AB  - BACKGROUND/AIMS: To evaluate the metabolic effects of meals with varying glycemic
      index (GI). METHODS: We measured the glucose, insulin and leptin responses to two
      contrasting breakfast cereals in a group of 10 young healthy volunteers. Meals
      were provided on two separate occasions in random order after a 12-hour overnight
      fast, and consisted of 50 g of available carbohydrate from either Corn Flakes
      (Kellogg's), or Fiber One (General Mills). Blood samples were obtained at rest,
      and 30, 60, 90 and 120 min after eating. The GI was calculated from the glucose
      response to the test meal normalized against a 50 g oral glucose load. RESULTS:
      The GI for Corn Flakes was 125 +/- 17 units and 49 +/- 8 units for Fiber One(R).
      These meals were classified as high GI and low GI, respectively, and were
      significantly different from each other (p < 0.0003). The area under the insulin
      response curve (AUC) following the low glycemic meal was significantly attenuated
      compared to the high glycemic meal (14,064 +/- 2,694 vs. 6,828 +/- 1,182
      pmol/l.min, p < 0.02). The leptin AUC revealed that circulating leptin was
      suppressed by the high glycemic meal compared to the low (3.1 +/- 1.5 vs. 9.6 +/-
      3.6 ng/ml.min, p < 0.04). CONCLUSIONS: Lower insulin and higher leptin suggests
      that low glycemic meals promote a postprandial metabolic milieu that is favorable
      for reduced food consumption; this may be advantageous in the control of obesity
      and related disorders including insulin resistance and type 2 diabetes.

PMID- 18073463
TI  - Can a peripheral artery be used to detect venous to arterial circulation shunts?
AB  - BACKGROUND: Transcranial Doppler is a sensitive test for patent foramen ovale
      (PFO), but an absent temporal window precludes this in 12-15% of patients. We
      investigated whether the brachial (BrA), common carotid (CCA) or common femoral
      (CFA) artery provided reliable alternatives. METHODS: Patients underwent
      simultaneous insonation of a middle cerebral artery (MCA, n = 66) and either (a)
      the BrA (n = 22), (b) CCA (n = 20) or (c) CFA (n = 24) with a 2-MHz transcranial
      Doppler probe. RESULTS: The correlation between microbubble emboli counts in the
      MCA and the peripheral arteries was (a) r = 0.67 (95% CI 0.53-0.77) for the BrA,
      (b) r = 0.80 (95% CI 0.71-0.87) for the CCA and (c) r = 0.92 (95% CI 0.89-0.95)
      for the CFA. The agreement for detection of PFO was best using the CFA with a
      kappa of 0.95 (95% CI 0.66-1.0). CONCLUSION: The CFA is a simple and reliable
      alternative to the MCA, but the criteria for diagnosis of a PFO are different.

PMID- 18073464
TI  - Chronic stroke longitudinal motor improvements: cumulative learning evidence
      found in the upper extremity.
AB  - BACKGROUND: The purpose was to determine the cumulative longitudinal effects of
      upper extremity distributed practice with variable treatment protocols involving
      EMG-triggered neuromuscular stimulation and coupled bilateral movements. METHODS:
      Sixteen chronic stroke subjects were randomly selected to complete 5 effective
      upper extremity treatment protocols over 12 months. The subjects were randomly
      assigned to 1 of 2 treatment orders. Consistent across the orders and protocols,
      the participants completed 90 min of training per day for 4 days during separate
      2-week rehabilitation periods. RESULTS: Data for the 5 primary outcome measures
      were analyzed in separate mixed design ANOVAs (treatment order x test session: 2
      x 6). The analyses revealed distinct cumulative treatment evidence later in
      training in comparison to the baseline motor capabilities: (1) higher number of
      blocks moved; (2) higher percentage of blocks moved by the impaired hand; (3)
      faster motor reaction time (peripheral component), and (4) faster total reaction
      time. CONCLUSIONS: These chronic stroke patients displayed robust cumulative
      motor improvement effects from the longitudinally distributed practice of active
      neuromuscular stimulation and coupled bilateral movements.

PMID- 18073465
TI  - Association between human paraoxonase 1 activity and intima-media thickness in
      subjects under 55 years of age with carotid artery disease.
AB  - BACKGROUND: Human serum paraoxonase (PON1) protects lipoproteins against
      oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein
      (oxLDL); therefore, it may protect against atherosclerosis. PON1 activity and
      polymorphisms have been inconsistently associated with carotid artery disease.
      The goal of this study was to clarify the role of PON1 activity and phenotype on
      carotid artery disease and its correlation with some inflammatory and immune
      markers in subjects under 55 years with early-onset carotid atherosclerosis.
      METHODS: Sixty patients with occlusive carotid artery disease and 30 healthy
      controls were enrolled. Intima-media thickness (IMT) was measured by high
      resolution ultrasound of both common carotid arteries. Anti-oxLDL antibody levels
      were determined by ELISA. RESULTS: In the whole study population we found a
      negative correlation between PON1 activity and IMT (r = -0.27, p = 0.011), and
      between salt-stimulated PON1 activity and IMT (r = -0.24, p = 0.02). Both PON1
      activity and salt-stimulated PON1 activity negatively correlated with anti-oxLDL
      levels (r = -0.28, p = 0.008; r = -0.26, p = 0.01). PON1 activity was lower in
      patients compared to controls; however, the difference was not significant.PON1
      phenotype distribution of patients and controls did not differ significantly.
      CONCLUSION: The importance of PON1 activity as a predictive risk factor for early
      onset occlusive carotid artery disease should be assessed in future studies.

PMID- 18073466
TI  - Intravenous thrombolysis with rt-PA in acute ischemic stroke patients aged older
      than 80 years in Italy.
AB  - BACKGROUND: Intravenous (i.v.) thrombolysis with rt-PA within 3 h from symptom
      onset is the only approved treatment of pharmacological revascularization in
      acute ischemic stroke. However, little information exists on its use in elderly
      patients, in particular those aged >80 years, who at present are excluded from
      treatment. METHODS: In a multicenter Italian study on i.v. thrombolysis, patients
      aged >80 years (n = 41) were compared with those aged <or=80 years (n = 207)
      regarding the percentage of symptomatic (nonfatal and fatal) intracerebral
      hemorrhage (SICH), favorable 3-month functional outcome (modified Rankin Scale
      score 0-2) and poor outcome (death or dependence, i.e. modified Rankin Scale
      score 3-5). RESULTS: The percentage of SICH (nonfatal and fatal) was comparable
      between older (2.4%, 2.4%) and younger (2.4%, 2.4%) patient groups (p = 1.0). At
      3 months, favorable outcome occurred in 44% and dependence in 22% of the older,
      and respectively in 58.5 and in 30.9% of the younger patients (p = 0.897).
      Patients aged >80 years had a higher mortality (34.1%) as compared to those aged
      <or=80 years (10.6%) (p < 0.001). Baseline National Institute of Health Stroke
      Scale score was the only statistically significant predictor of both mortality
      (OR = 1.26; 95% CI = 1.07-1.50) and poor outcome (OR = 1.39; 95% CI = 1.14-1.68)
      in the >80-year-old group. CONCLUSIONS: Acute ischemic stroke patients aged >80
      years treated with i.v. rt-PA have a higher mortality than younger patients, but
      there are no differences for SICH nor for favorable outcome. Our data suggest
      that thrombolytic therapy should not be a priori denied for appropriately
      selected >80-year-old patients but randomized controlled clinical trials are
      necessary before definite recommendations can be given.

PMID- 18073467
TI  - Effect of age and glycaemic control on the association between fibrinogen and
      risk of acute coronary events after transient ischaemic attack or stroke.
AB  - BACKGROUND: Fibrinogen is an independent risk factor for acute vascular events,
      but there is uncertainty as to whether it is causal. One potential causal
      mechanism is the formation of low permeability fibrin clot in association with
      raised fibrinogen. We hypothesised that if this effect of fibrinogen were
      causally related to risk of vascular events, the risk relationship would be
      affected by the two other factors that affect fibrin clot permeability - age and
      glycaemic control. METHODS: We studied the relationship between fibrinogen and
      risk of incident coronary events by age and baseline glucose levels in pooled
      data from three cohorts of patients with known cerebrovascular disease (UK-TIA
      Aspirin trial; Dutch TIA trial; Oxford TIA Study) during 23,272 patient-years of
      follow-up. RESULTS: Risk of coronary events increased linearly with fibrinogen,
      but there was a significant interaction with age (p = 0.01 across tertiles of
      age), with the association being strongest for individuals aged <60 years (upper
      fibrinogen quintile hazard ratio = 3.95, 95% CI = 2.67-5.85, p < 0.0001). The
      risk relation was diminished in individuals with impaired glucose tolerance or
      diabetes. The effects of age and glycaemic control were independent, such that
      there was an almost fivefold increase in risk across quintiles of fibrinogen in
      patients aged <60 years with below median normal glucose levels (upper quintile
      hazard ratio = 4.90, 95% CI = 2.79-8.58, p < 0.0001). CONCLUSIONS: The effect of
      age and glycaemic control on the relationship between fibrinogen and risk of
      acute coronary events supports the hypothesis of a causal effect of fibrinogen
      mediated via the permeability of fibrin clot.

PMID- 18073468
TI  - Prospective evaluation of multidetector-row CT angiography for the diagnosis of
      vasospasm following subarachnoid hemorrhage: a comparison with digital
      subtraction angiography.
AB  - PURPOSE: To evaluate the accuracy of multidetector-row CT angiography (CTA) for
      the diagnosis of large-vessel vasospasm following subarachnoid hemorrhage by
      comparison to digital subtraction angiography (DSA). METHODS: Thirty-three
      patients with acute subarachnoid hemorrhage were enrolled in a prospective study
      and underwent a total of 40 CTA and DSA examinations within 24 h of each other.
      Two neuroradiologists reviewed the CTA examinations independently. A third
      neuroradiologist blinded to the CTA results reviewed the DSA examinations. In
      each patient, for both techniques, 23 arterial segments were evaluated for their
      degree of narrowing; the reviewers were asked to attribute every narrowing to
      'vasospasm' or 'hypoplasia'. Agreement between CTA and DSA for the degree of
      narrowing, and agreement between the two CTA readers, were calculated using
      weighted kappa-coefficients. Sensitivity, specificity, accuracy, positive and
      negative predictive value (NPV) of CTA to detect large-vessel vasospasm were
      calculated considering DSA as the gold standard. RESULTS: Substantial correlation
      (kappa = 0.638) was found between CTA and DSA for the detection of arterial
      narrowing. Interobserver agreement between the two CTA reviewers for the degree
      of luminal narrowing was substantial (kappa = 0.712).CTA was 87% accurate for the
      diagnosis of large-vessel vasospasm; the NPV of CTA was 95%. CTA was more
      accurate, and interobserver agreement higher, for the proximal arterial segments
      (basilar and vertebral arteries) than for the distal ones (P2 segments). Using
      CTA as a screening modality, 83% of unnecessary DSA would have been avoided.
      CONCLUSION: Compared to the gold standard of DSA, CTA is accurate for the
      detection of large-vessel vasospasm, and has a very high NPV.

PMID- 18073470
TI  - Tigecycline in vitro activity against gram-negative and gram-positive pathogens
      collected in Italy.
AB  - BACKGROUND: In this study (part of the global TEST program), the in vitro
      activity of tigecycline, a member of a new class of antimicrobial agents, the
      glycylcyclines, against clinical isolates collected in Italy was evaluated.
      METHODS: A total of 200 clinical isolates were collected and identified in our
      institution during 2005. Minimum inhibitory concentrations (MICs) of the
      antimicrobial agents were determined by the broth microdilution method
      recommended by the CLSI in 2005. RESULTS: Globally, 135 Gram-negative and 65 Gram
      positive pathogens were evaluated. Tigecycline demonstrated excellent inhibitory
      activity against Acinetobacter spp., Haemophilus influenzae, Escherichia coli,
      Enterococcus spp., Staphylococcus aureus, Streptococcus agalactiae and
      Streptococcus pneumoniae with MIC(90) <or=1 mg/l. CONCLUSION: Tigecycline
      exhibited potent in vitro antibacterial activity (comparable to or greater than
      most commonly employed antimicrobials) against both Gram-positive and Gram
      negative clinical pathogens. These data suggest that tigecycline, with an
      expanded broad-spectrum antimicrobial activity, may be an effective empiric
      therapeutic option for the treatment of serious infections caused by clinically
      relevant pathogens.

PMID- 18073469
TI  - Activity of caspofungin and voriconazole against clinical isolates of Candida and
      other medically important yeasts by the CLSI M-44A disk diffusion method with Neo
      Sensitabs tablets.
AB  - In vitro activity of caspofungin and voriconazole against 184 clinical isolates
      of Candida and other medically important yeasts in comparison with that of
      fluconazole, ketoconazole, itraconazole and amphotericin B was determined by
      using a disk diffusion method (Neo-Sensitabs) standardized according to the
      recommendations of the CLSI documents M44-A and M44-S1 (same medium: Mueller
      Hinton plus methylene blue; inoculum and minimal inhibitory concentration/zone
      breakpoints). Seventy-two percent of clinical isolates were susceptible to
      caspofungin, 23.6% showed an intermediate susceptibility (most of them were
      Candida parapsilosis) and 4.3% were resistant (values for Candida spp. were 71.2,
      23.8 and 5%, respectively). For voriconazole, 96.7% of clinical isolates were
      susceptible and 3.3% were resistant (Candida spp.: 96 and 3.8%, respectively).
      Both caspofungin and voriconazole showed high activity against a wide variety of
      clinically important yeasts.

PMID- 18073471
TI  - Levofloxacin-resistant Helicobacter pylori in Hong Kong.
AB  - BACKGROUND: Fluoroquinolone-resistant Helicobacter pylori emerged in 1995 and the
      resistance was due to point mutation in the gyrA gene. In this study we
      investigate the resistance mechanism and the antimicrobial susceptibilities of
      clarithromycin, metronidazole, amoxicillin, tetracycline and telithromycin
      against levofloxacin-resistant H. pylori in Hong Kong. METHODS: One hundred and
      ninety-one nonduplicate H. pylori isolates were collected during 2004 and 2005,
      and 25 isolates with levofloxacin zone sizes less than 30 mm were selected for
      minimal inhibitory concentration determination by agar dilution, gyrA gene
      amplication and sequencing the amplified gyrA gene. RESULTS: The prevalence of
      levofloxacin-resistant H. pylori was 11.5% (22/191). Among these levofloxacin
      resistant strains, 7 (31.8%) and 10 (45.5%) were resistant to clarithromycin and
      metronidazole, respectively, 17 (77.3%) had point mutations in gyrA gene at amino
      acids 87, 91 and 130 and the most frequent mutation point was at position 91.
      CONCLUSIONS: Amoxicillin, tetracycline and telithromycin were active against
      levofloxacin-resistant H. pylori and levofloxacin resistance was mainly due to
      point mutation in the gyrA gene, especially at amino acid position 91.

PMID- 18073472
TI  - Fixed dose rate infusion of gemcitabine with oral doxifluridine and leucovorin
      for advanced unresectable pancreatic cancer: a phase II study.
AB  - The standard beneficial chemotherapy proven for patients with advanced pancreatic
      cancer is a regimen containing gemcitabine. In the pregemcitabine era, 5
      fluorouracil (5-FU) was the standard agent. Oral 5-FU can be added to gemcitabine
      to improve the efficacy of chemotherapy and to provide better patient
      convenience. The possibility to improve efficacy of gemcitabine by fixed dose
      rate infusion (FDRI) was proposed in addition to combining it with 5-FU. We tried
      a new chemotherapy combining FDRI of gemcitabine with doxifluridine and
      leucovorin. Eligibility criteria were pathologically proven, chemotherapy-naive,
      and metastatic or nonoperable advanced pancreatic cancer. Gemcitabine 1,000
      mg/m(2) was infused over 100 min (days 1, 8 and 15). Doxifluridine 200 mg/m(2)
      t.i.d. and leucovorin 15 mg b.i.d. were given orally (days 1-21). Chemotherapy
      was repeated every 28 days until a patient had received 6 cycles or progression
      was found. Twenty-nine patients were enrolled from October 2002 to December 2004.
      A total of 78 cycles were given at a mean of 2.7 cycles per patient. Response
      could be evaluated in 26 patients. Responses were partial remission in 4/26
      patients (15.4%), stable disease in 8/26 (30.8%) and progression in 14/26
      (53.8%). All patients progressed except for 2 in partial remission and 2 in
      stable disease. Toxicities could be assessed in 23 patients. Maximal
      hematological toxicities greater than grade 2 were leucopenia in 3 patients
      (11.5%), neutropenia in 2 (7.7%), anemia in 2 (7.7%), thrombocytopenia in 1
      (3.8%) and febrile neutropenia in 3 (11.5%). Maximal nonhematological grade 3 or
      4 toxicities were asthenia in 1 patient (3.8%), anorexia in 1 (3.8%), vomiting in
      1 (3.8%), diarrhea in 2 (7.7%), allergic reaction in 1 (3.8%), hand-foot syndrome
      in 1 (3.8%) and hyperbilirubinemia in 1 (3.8%). All 29 patients were dead on last
      follow-up. Median progression-free survival was 3.91 months in 26 evaluable
      patients and median overall survival was 5.59 months in all patients. Combination
      chemotherapy including FDRI of gemcitabine seems minimally active for patients
      with advanced, nonoperable pancreatic cancer. Further research to improve
      effectiveness of chemotherapy for advanced pancreatic cancer is mandatory.

PMID- 18073473
TI  - Cervical actinomycosis with spinal cord compression. Case report and literature
      review.
AB  - Cervical actinomycosis with spinal cord compression is extremely rare. The
      clinical presentation of spinal actinomycosis may be nonspecific and back pain is
      the most consistent early symptom. Here, we present such a case with fever, pain
      in the neck and upper back, progressive weakness and numbness in all 4 limbs with
      difficulty ambulating, constipation and uroschesis. Correct diagnosis is
      difficult because the clinical and radiological findings of actinomycosis closely
      resemble metastatic tumors and other infectious processes. Timely surgical
      debridement and decompression contributed to the prompt improvement of the
      patient's conditions, and histopathological demonstration of the inflammatory
      granulation tissue and Gram-positive sulfur-containing filamentous bacteria led
      to the correct diagnosis of actinomycosis. The diagnosis must be made promptly
      because delayed treatment can result in irreversible neurologic damage or death.
      Timely and long-term antibacterial therapy is essential for the complete recovery
      of the patient with actinomycosis.

PMID- 18073474
TI  - Role of triptolide as an adjunct chemotherapy for ovarian cancer.
AB  - BACKGROUND: Triptolide (TPL) has been identified as the active component of the
      Tripterygium wilfordii hook F plant and demonstrated to possess antitumor
      properties and induce apoptosis in a variety of tumor cell lines. Since TPL
      actions are associated with changes in the activities of both p53 and NF kappaB,
      which are implicated in the chemoresistance of ovarian cancer, the ability of TPL
      to be a potential chemotherapeutic for ovarian cancer was considered. METHODS:
      TPL actions on human ovarian cancer cells were investigated in vitro and in vivo
      with a nude mouse model to monitor tumor burden both in the absence or presence
      of other chemotherapy agents. RESULTS: TPL was effective as a single agent in
      inducing apoptosis of ovarian cancer cells in vitro, but not in vivo. TPL
      enhanced the cytotoxicity of carboplatin in culture and enhanced carboplatin
      mediated reduction of tumor burden in nude mice inoculated with human ovarian
      cancer cells. Previously, a phosphatidylinositol 3-kinase (PI3 kinase) inhibitor
      was found to enhance carboplatin actions on ovarian cancer. Interestingly, the
      combined treatment of TPL, PI3 kinase inhibitor LY294002 and carboplatin was
      found to dramatically reduce ovarian tumor progression and burden in nude mice.
      CONCLUSION: In 44% of the animals tested the combined treatment caused complete
      regression of ovarian cancer. Combined observations indicate TPL may be an
      effective adjunct chemotherapy for ovarian cancer.

PMID- 18073475
TI  - Prognostic value of natriuretic peptides in Chagas' disease: a 3-year follow-up
      investigation.
AB  - BACKGROUND: Chagas' disease (CD) affects around 18 million people in Latin
      America. To determine the diagnostic and prognostic value of natriuretic peptides
      in patients with CD, we measured atrial (ANP) and brain natriuretic peptide
      (BNP), and compared the findings with other dilated cardiomyopathies (DCM).
      METHODS: Blood samples were obtained from 111 CD patients, 62 patients with DCM
      due to other causes, and 43 gender- and age-matched healthy subjects. The CD and
      DCM patients were subdivided according to their NYHA classification. Natriuretic
      peptide concentrations were determined by immunoradiometric assays. RESULTS: ANP
      and more pronounced BNP levels were increased in CD and DCM patients in relation
      to the NYHA class. Circulating BNP concentrations were higher in CD patients in
      NYHA classes I-II than in the corresponding DCM patients (p = 0.020).
      Importantly, ANP and BNP were already significantly elevated in CD patients
      without systolic ventricular dysfunction (p < or = 0.001). In CD patients, both
      peptides were highly correlated with echocardiographic parameters (p < 10(-14)).
      Both ANP and BNP had comparable ability to predict death or the necessity for
      heart transplant (p < 0.0001). CONCLUSION: Natriuretic peptide levels can be used
      as a marker of asymptomatic CD without ventricular dysfunction and thus could be
      an ideal tool to identify these patients for early therapy.

PMID- 18073476
TI  - Extremely late pacemaker-infective endocarditis due to Stenotrophomonas
      maltophilia.
AB  - This case report describes a patient with an intravascular infection of a
      pacemaker system with Stenotrophomonas maltophilia, which occurred 17 years after
      the implantation. The patient was treated with appropriate antibiotics and
      debridement of the infectious tissue in the pocket, and the entire pacemaker
      system was removed by open heart surgery. She was discharged from our center
      after a 6-week course of antibiotics and implantation of a new pacemaker.

PMID- 18073477
TI  - Effects of chronic therapy with cardiac contractility modulation electrical
      signals on cytoskeletal proteins and matrix metalloproteinases in dogs with heart
      failure.
AB  - OBJECTIVES: Therapy with cardiac contractility modulation (CCM) electrical
      signals delivered to left ventricular (LV) muscle during the absolute refractory
      period improves LV systolic and diastolic function in dogs with heart failure
      (HF). This study examined the effects of CCM therapy on mRNA and protein
      expression of cytoskeletal proteins, matrix metalloproteinases (MMPs) and tissue
      inhibitors of MMPs (TIMPs) in the LV myocardium of dogs with HF. METHODS: HF was
      produced in 14 dogs by coronary microembolizations. Dogs were randomized to 3
      months of CCM therapy (n = 7) or to sham-operated controls (n = 7). LV tissue
      from 6 normal (NL) dogs was used for comparison. mRNA expression was measured
      using reverse-transcriptase polymerase chain reaction and protein expression
      using Western blots. RESULTS: Compared with NL dogs, controls showed upregulation
      of mRNA and protein expression of the cytoskeletal proteins tubulin and
      fibronectin and MMP-1, MMP-2 and MMP-9, and downregulation of the cytoskeletal
      protein titin. Normalized expression of all these genes and proteins was seen
      after CCM therapy. No differences in expression of TIMP-1 and TIMP-2 were
      observed among groups. CONCLUSIONS: CCM therapy normalizes expression of key
      cytoskeletal proteins and MMPs and may partly explain the improvement in LV
      function seen in HF following CCM therapy.

PMID- 18073478
TI  - Progressive mitral valve thickening and progressive muscle cramps as
      manifestations of glycogenosis VII (Tarui's Disease).
AB  - Progressive heart valve thickening and shrinkage, and progressive muscle cramps
      have not been reported as manifestations of glycogenosis type VII (Tarui's
      disease). In a 72-year-old female, Tarui's disease was diagnosed in 1997,
      initially manifesting as simple partial seizures since 1977, anginal chest pain
      since 1982 and muscle cramps since 1983. During the following years, low voltage
      ECG, ectopic supraventricular tachycardia, thickening of the mitral valve, mitral
      valve insufficiency, enlarged left atrium, left ventricular hypertrophy and
      diastolic dysfunction also developed. Neurological manifestations progressed to
      complex partial seizures, double vision, reduced tendon reflexes, central facial
      palsy, bradydiadochokinesia, distal weakness of the upper extremities and
      worsening muscle cramps. Thickening and shrinkage of the heart valves had further
      increased at 72 years of age. Progression of Tarui's disease may manifest as
      progressive thickening of the heart valves due to glycogen storage. Valve
      thickening may consecutively lead to valve insufficiency, enlargement of the
      atrium and atrial fibrillation. Progression of neurological manifestations may
      manifest as worsening muscle cramps.

PMID- 18073479
TI  - Is there a relation between non-calcifying coronary plaques and acute coronary
      syndromes? A retrospective study using multislice computed tomography.
AB  - OBJECTIVES: The purpose of this study was to assess whether different coronary
      plaque types as classified by multislice computed tomography (CT) are
      retrospectively correlated with acute coronary syndromes (ACS) in an unselected
      study population. METHODS: Sixty-three consecutive patients were examined with 16
      slice CT coronary angiography. Coronary plaque types were classified as
      calcifying type 1, mixed (calcifying > non-calcifying) type 2, mixed (non
      calcifying > calcifying) type 3, and non-calcifying type 4. Patients who had an
      ACS within 17 days were included. All patients underwent invasive coronary
      angiography. RESULTS: Fifty-eight patients (92%) had coronary plaques evaluated
      by CT: 18 type 1 (31%), 10 type 2 (17%), 16 type 3 (28%) and 14 type 4 (24%). The
      presence of a non-calcifying plaque component (types 2-4; 40 of 63 patients, 63%)
      was correlated with ACS (n = 15; 24%) (p < 0.001). Only type 3 was significantly
      correlated with ACS (p = 0.01), but plaque types 2 and 4 were not. The diagnostic
      accuracy of CT for detection of stenosis >50% in proximal segments was:
      sensitivity 98%, specificity 90%, negative predictive value 97%, positive
      predictive value 97% per patient. CONCLUSIONS: Mixed calcifying/non-calcifying
      plaques with a predominantly non-calcifying component (type 3) as classified by
      multislice CT are retrospectively correlated with ACS.

PMID- 18073480
TI  - Pulmonary artery aneurysm as a cause for chest pain in a patient with Noonan's
      syndrome: a case report.
AB  - A pulmonary artery aneurysm is defined as pulmonary artery dilatation >4 cm.
      Pulmonary artery aneurysms are rare findings and are usually not associated with
      chest pain. This is the first report of a case of pulmonary artery aneurysm
      causing chest pain in a patient with Noonan's syndrome. Chest X-ray showed
      cardiomegaly and a prominent main pulmonary artery segment and CT confirmed a
      pulmonary artery aneurysm with a pulmonary artery root measuring 5.6 cm. The
      patient underwent pulmonary valvuloplasty as well as pulmonary arterioplasty to
      repair the pulmonary artery aneurysm, and experienced subsequent relief of chest
      pain. In conclusion, pulmonary artery aneurysm is a rare complication in patients
      with Noonan's syndrome and can be the cause of chest pain in such patients.

PMID- 18073482
TI  - Association of connexin 37 gene polymorphisms with risk of coronary artery
      disease in northern Han Chinese.
AB  - BACKGROUND: Recently, the C1019T polymorphism in the human gene encoding connexin
      37 (CX37, encoded by GJA4) has been reported to be associated with coronary
      artery disease (CAD)/myocardial infarction in different racial groups, but no
      data are currently available in northern Han Chinese. The aim of our study is to
      investigate the association between 3 GJA4 gene polymorphisms (-1930C/T, C1019T
      and I1297D) and the susceptibility to CAD in northern Han Chinese. METHODS: 502
      CAD patients and 410 controls confirmed by coronary angiography were genotyped by
      polymerase chain reaction restriction fragment length polymorphism analysis in an
      independent case-control study. RESULTS: The overall distribution of GJA4 C1019T
      genotypes among CAD patients and healthy controls was significantly different (p
      < 0.01). Frequencies of C1019T CC homozygote and C allele were significantly
      higher in the patient group than those in the control group. Stratification
      analysis showed that the C1019T C allele significantly increased the risk of CAD
      only among male subjects (p = 0.006; OR 1.38; 95% CI 1.09-1.74). After adjustment
      for conventional risk factors, binary logistic regression analysis showed that
      the C allele carrier (CC + CT) of C1019T was an independent risk factor for CAD
      (p < 0.05). Further linkage disequilibrium tests and haplotype analysis revealed
      that the C-C-D haplotype conferred an increased risk of CAD. CONCLUSIONS: Our
      study suggests that GJA4 gene C1019T polymorphism and/or its related C-C-D
      haplotype might contribute to an increased risk of CAD and potentially play an
      important role in the development of coronary atherosclerosis in northern Han
      Chinese.

PMID- 18073481
TI  - Oxidized low-density lipoproteins, autoantibodies against oxidized low-density
      lipoproteins and carotid intima media thickness in a clinically healthy
      population.
AB  - BACKGROUND: Oxidized low-density lipoproteins (oxLDLs) play an important role in
      the progress of atherosclerosis. Autoantibodies (oxLDL Ab) against oxLDLs may
      reflect the extent of LDL oxidation in vivo. Our aim was to investigate the
      correlation between oxLDLs, oxLDL Ab and intima media thickness of the common
      carotid arteries (CCA-IMT) in a clinically healthy population. METHODS: Two
      hundred subjects were recruited, and demographic and clinical characteristics of
      the subjects were recorded. By use of tertile classification of plasma oxLDLs and
      oxLDL Ab, 9 groups including 4 extreme subject groups were generated. CCA-IMT was
      measured as an indicator of carotid atherosclerosis. RESULTS: Age and plasma LDL
      concentration contributed significantly to CCA-IMT (p < 0.05). Body mass index,
      smoking index and plasma LDL concentration were significantly positively related
      to the plasma oxLDLs concentration; by contrast, plasma oxLDL Ab were
      significantly negatively related to the plasma oxLDL concentration (p < 0.05).
      Subjects in the group with low oxLDL Ab/high oxLDLs had the greatest CCA-IMT and
      the highest level of LDL; by contrast, subjects in the group with high oxLDL
      Ab/low oxLDLs had the least CCA-IMT and the lowest level of LDL. CONCLUSIONS:
      Both plasma oxLDLs and oxLDL Ab contribute, although in opposite ways, to the LDL
      metabolism and development of atherosclerosis. Immune response to oxLDLs may
      exert a protective role at an early stage of atherosclerosis.

PMID- 18073483
TI  - Brain natriuretic peptide levels predict perioperative events in cardiac patients
      undergoing noncardiac surgery: a prospective study.
AB  - OBJECTIVES: Brain natriuretic peptide (BNP) levels correlate with prognosis in
      patients with cardiac disease and may be useful in the risk stratification of
      cardiac patients undergoing noncardiac surgery (NCS). The objective of this study
      was to examine whether BNP levels predict perioperative events in cardiac
      patients undergoing NCS. METHODS: Patients undergoing NCS with at least 1 of the
      following criteria were included: a clinical history of congestive heart failure
      (CHF), ejection fraction <40%, or severe aortic stenosis. All patients underwent
      echocardiography and measurement of BNP performed using the ADVIA-Centaur BNP
      assay (Bayer HealthCare). Clinical endpoints were death, myocardial infarction or
      pulmonary congestion requiring intravenous diuretics at 30 days of follow-up.
      RESULTS: Forty-four patients were entered into the study; 15 patients (34%)
      developed cardiac postoperative complications. The mean BNP level was 1,366 +/-
      1,420 pg/ml in patients with events and 167 +/- 194 pg/ml in patients without
      events, indicating a highly significant difference (p < 0.001). The ROC area
      under the curve was 0.91 (95% CI 0.83-0.99) with an optimal cutoff of >165 pg/ml
      (100% sensitivity, 70% specificity). CONCLUSIONS: BNP levels may predict
      perioperative complications in cardiac patients undergoing NCS, and the
      measurement of BNP should be considered to assess the preoperative cardiac risk.

PMID- 18073484
TI  - An apolipoprotein A-I gene promoter polymorphism associated with cognitive
      decline, but not with Alzheimer's disease.
AB  - BACKGROUND/AIMS: Accumulating biological and epidemiological evidence suggests a
      close link between cholesterol metabolism and the pathophysiology of Alzheimer's
      disease (AD). The observation that the use of statins reduces the risk of AD
      sustains this hypothesis. Apolipoprotein A-I (APOA1) is the major component of
      the high-density lipoproteins, particles involved in reverse cholesterol
      transport. Therefore, genetic polymorphisms in the gene encoding APOA1 might
      influence cholesterol metabolism and be a risk factor for AD. A previous study
      suggested an impact of a G-->A polymorphism at position -75 bp in the APOA1 gene
      on the risk for early-onset AD and on the age at onset of the disease. We studied
      this polymorphism in 3 independent European population samples. METHODS:
      Genotyping was conducted asdescribed in the previous study. RESULTS: We were
      unable to show any impact of this polymorphism on the risk of AD. Conversely,
      subjects bearing the A allele of this polymorphism were at risk of cognitive
      decline. CONCLUSION: Our resultssuggest an impact of the G-->A polymorphism at
      position -75 bp in the APOA1 gene on cognitive impairment, but not on the risk of
      AD.

PMID- 18073485
TI  - Obstetric characteristics for a prolonged third stage of labor and risk for
      postpartum hemorrhage.
AB  - AIM: To determine the obstetric characteristics associated with a prolonged third
      stage of labor and risk factors for a postpartum hemorrhage (PPH) in women
      undergoing vaginal delivery. METHOD: Secondary analysis of a prospective
      randomized investigation comparing placental removal at 20 versus 30 min to
      prevent PPH. RESULTS: Between 1 March 2004 and 1 March 2005, 1,607 women were
      recruited. Eighty-nine percent of the placentas had delivered by 10 min (n =
      1,430) and 10.5% (n = 168) had delivered between 10 and 20 min, leaving 8
      retained placentas (0.5%) >20 min. Simultaneous factors predictive of longer
      duration of third stage of labor included maternal age > or =35 years (hazard
      ratio HR = 0.990, 95% CI 0.981-0.999, p = 0.030) and duration of second stage of
      labor >2 h (HR = 0.745, 95% CI 0.628-0.883, p = 0.001) relative to second stage
      of labor <1 h. Significant risk factors for PPH included chorioamnionitis (odds
      ratio OR = 6.45, 95% CI 2.37-17.64, p < 0.001), nulliparity (OR = 2.38, 95% CI
      1.19-4.77, p = 0.014), overdistended uterus (OR = 2.81, 95% CI 1.02-7.76, p =
      0.047) and third stage of labor >10 min (OR = 6.45 95%, CI 2.73-22.84, p < 0.001
      compared with third stage < or =5 min). CONCLUSIONS: Prolonged third stage of
      labor is correlated with an older maternal age and a prolonged second stage of
      labor. Significant risk factors for PPH include chorioamnionitis, an
      overdistended uterus and a third stage of labor >10 min.

PMID- 18073486
TI  - Spontaneous regression of a breast carcinoma: a case report.
AB  - Spontaneous regression of malignant tumors is a rare event. It is defined as
      partial or total disappearance of a proven malignant tumor without adequate
      medical treatment. The causes of this phenomenon are various. Nevertheless,
      malignant tumors do regress occasionally for no apparent reason, as evidenced by
      many clinical observations. We report a case of a 68-year-old woman, who was
      presented with a several-month history of a painless firm lump, initially of 1 cm
      in diameter and growing to a large solid regular tumor of 2.5 x 2.5 cm in size,
      in the upper outer quadrant of her right breast. Preoperative histopathological
      diagnosis revealed ductal invasive carcinoma. Later on, while awaiting surgical
      treatment, she suffered an arm injury requiring a 1-month delay of surgery. After
      recovery, on the date of surgery the tumor disappeared, and, in addition, it was
      not found in tissue specimens obtained from quadrantectomy. After 78 months of
      follow-up there was no evidence of relapse. In this report, we discuss clinical
      and histopathological findings, patient management and possible mechanisms of
      cancer regression.

PMID- 18073487
TI  - In vitro fertilization in normoresponder patients with endometriomas: comparison
      with basal simple ovarian cysts.
AB  - OBJECTIVE: To investigate whether the space-occupying effect of an endometrioma,
      rather than endometriosis itself, affects results in in vitro fertilization (IVF)
      using women with simple ovarian cysts as the control group. METHODS: 85
      normoresponder patients with endometriomas of 10-50 mm who underwent IVF
      treatment directly without initial removal were compared with 83 normoresponder
      patients with simple ovarian cysts of 10-35 mm detected at the beginning of
      stimulation and initiated treatment without aspiration. RESULTS: Gonadotropin
      consumption was higher in the endometrioma group (3,013 vs. 2,451 IU; p = 0.001),
      although significantly fewer numbers of oocytes were retrieved (13.9 vs. 16.4; p
      = 0.03). However, oocyte maturation rates were similar. The transferred grade I
      embryos ratio was evaluated and found to be better in the cyst group (79.7 vs.
      70.7%; p = 0.03). Consequently, the implantation rate was found to be
      significantly higher in the cyst group (28 vs. 19%; p = 0.02), although pregnancy
      and ongoing pregnancy rates were similar. CONCLUSION: The presence of an
      endometriotic cyst during the IVF cycle was demonstrated to be associated with a
      lower embryo quality and implantation rate, although pregnancy success was
      unaffected. This adverse effect is suggested to be the result of the disease
      itself, not the presence of a cystic mass.

PMID- 18073488
TI  - Universal false discovery rate estimation methodology for genome-wide association
      studies.
AB  - Genome-wide case-control association studies aim at identifying significant
      differential markers between sick and healthy populations. With the development
      of large-scale technologies allowing the genotyping of thousands of single
      nucleotide polymorphisms (SNPs) comes the multiple testing problem and the
      practical issue of selecting the most probable set of associated markers. Several
      False Discovery Rate (FDR) estimation methods have been developed and tuned
      mainly for differential gene expression studies. However they are based on
      hypotheses and designs that are not necessarily relevant in genetic association
      studies. In this article we present a universal methodology to estimate the FDR
      of genome-wide association results. It uses a single global probability value per
      SNP and is applicable in practice for any study design, using any statistic. We
      have benchmarked this algorithm on simulated data and shown that it outperforms
      previous methods in cases requiring non-parametric estimation. We exemplified the
      usefulness of the method by applying it to the analysis of experimental
      genotyping data of three Multiple Sclerosis case-control association studies.

PMID- 18073489
TI  - Genetics and gene-environment interactions in atopic diseases. The Norwegian
      Mother and Child Cohort Study.
AB  - OBJECTIVES: The Norwegian Mother and Child Cohort Study (MoBa) aims to provide
      new insights in a broad variety of diseases. The goal of the study is to
      understand pathways in disease development, and identify preventive measures.
      Several designs are suitable for studying genetics in complex diseases like
      asthma and allergy, in MoBa. METHODS: MoBa is a prospective population based
      cohort of 100 000 pregnancies, following offspring into adulthood. Enrollment
      started in 1999, and will be completed in 2008. A biobank with samples from the
      mother, father and child, together with detailed questionnaires from early
      pregnancy and childhood constitute the basis of the study. When studying complex
      diseases like asthma, a design with case-parent triads is useful. Parental
      effects and interactions between maternal and fetal genes can be detected.
      Stratifying triads by environmental exposure enables assessment of gene
      environment interactions. RESULTS: By July 2006, more than 73,000 pregnancies
      have been included, with nearly 7,000 siblings and 1,300 pairs of twins enrolled.
      Biological samples are processed and stored at the biobank. The first children
      are reaching age seven in 2006. CONCLUSION: The MoBa cohort provides an excellent
      basis for studying genetic, epigenetic and environmental influences on complex
      diseases.

PMID- 18073490
TI  - Ignoring intermarker linkage disequilibrium induces false-positive evidence of
      linkage for consanguineous pedigrees when genotype data is missing for any
      pedigree member.
AB  - Missing genotype data can increase false-positive evidence for linkage when
      either parametric or nonparametric analysis is carried out ignoring intermarker
      linkage disequilibrium (LD). Previously it was demonstrated by Huang et al. [1]
      that no bias occurs in this situation for affected sib-pairs with unrelated
      parents when either both parents are genotyped or genotype data is available for
      two additional unaffected siblings when parental genotypes are missing. However,
      this is not the case for autosomal recessive consanguineous pedigrees, where
      missing genotype data for any pedigree member within a consanguinity loop can
      increase false-positive evidence of linkage. False-positive evidence for linkage
      is further increased when cryptic consanguinity is present. The amount of false
      positive evidence for linkage, and which family members aid in its reduction, is
      highly dependent on which family members are genotyped. When parental genotype
      data is available, the false-positive evidence for linkage is usually not as
      strong as when parental genotype data is unavailable. For a pedigree with an
      affected proband whose first-cousin parents have been genotyped, further
      reduction in the false-positive evidence of linkage can be obtained by including
      genotype data from additional affected siblings of the proband or genotype data
      from the proband's sibling-grandparents. For the situation, when parental
      genotypes are unavailable, false-positive evidence for linkage can be reduced by
      including genotype data from either unaffected siblings of the proband or the
      proband's married-in-grandparents in the analysis.

PMID- 18073491
TI  - Utah family-based analysis: past, present and future.
AB  - A unique genealogical resource linked to phenotype data was created in Utah over
      30 years ago. Here we review the history and content of this resource. In
      addition, we review three current methodologies used in conjunction with this
      resource to define the heritable contribution to phenotypes and to identify
      predisposition genes responsible for these phenotypes. Example analyses and high
      risk pedigrees are presented. Finally we briefly review ways this resource, or
      others like it, may expand in future.

PMID- 18073492
TI  - Adjusting for founder relatedness in a linkage analysis using prior information.
AB  - In genetic linkage studies, while the pedigrees are generally known, background
      relatedness between the founding individuals, assumed by definition to be
      unrelated, can seriously affect the results of the analysis. Likelihood
      approaches to relationship estimation from genetic marker data can all be
      expressed in terms of finding the most likely pedigree connecting the individuals
      of interest. When the true relationship is the main focus, the set of all
      possible alternative pedigrees can be too large to consider. However, prior
      information is often available which, when incorporated in a formal and
      structured way, can restrict this set to a manageable size thus enabling the
      calculation of a posterior distribution from which inferences can be drawn. Here,
      the unknown relationships are more of a nuisance factor than of interest in their
      own right, so the focus is on adjusting the results of the analysis rather than
      on direct estimation. In this paper, we show how prior information on founder
      relationships can be exploited in some applications to generate a set of
      candidate extended pedigrees. We then weight the relevant pedigree-specific
      likelihoods by their posterior probabilities to adjust the lod score statistics.

PMID- 18073493
TI  - Association of low-density lipoprotein receptor-related protein 5 (LRP5) promoter
      SNP with peak bone mineral density in Chinese women.
AB  - OBJECTIVE: Low-density lipoprotein receptor-related protein 5 (LRP5) is important
      for osteoblast differentiation and mutations of the gene are associated with both
      low and high bone mass syndromes. Our study aimed to evaluate the importance of
      LRP5 in the determination of peak bone mass acquisition in Chinese females in the
      general population. METHODS: A total of 286 young southern Chinese females (aged
      22-44 years) with low bone mineral density (BMD) (defined by a BMD Z score < or =
      1.28 at either the hip or spine) or high BMD (Z score > or =+1) were studied. The
      LRP5 gene was sequenced for single nucleotide polymorphisms (SNPs) and 4 SNPs
      were tagged from 8 genotyped SNPs for this study. RESULTS: Single locus allele
      association tests revealed significant associations of rs682429 and rs686921 with
      BMD variation (p < 0.05). Omnibus test (likelihood ratio test) revealed overall
      significant association between LRP5 gene locus and total hip BMD, with rs682429
      being most predictive. rs682429 is located in 5'UTR, 2 bases adjacent to a
      consensus recognition site for the Elk-1 binding element. CONCLUSION: Common
      variations of the LRP5 promoter are associated with BMD in young women. These
      significant associations appear to be driven by rs682429. Functional studies are
      necessary to elucidate the role of this SNP on the effect of Elk-1 binding
      element transcriptional activity of LRP5 gene.

PMID- 18073494
TI  - Reported hearing impairment in essential tremor: a population-based case-control
      study.
AB  - In a population-based sample, we determined whether a larger proportion of
      essential tremor (ET) cases reported hearing impairment compared with controls.
      Ninety-six (38.7%) of 248 ET cases versus 1,371 (29.4%) of 4,669 controls (p =
      0.002) reported hearing impairment. In a logistic regression analysis adjusted
      for age, gender, educational level, depressive symptoms, and dementia,
      participants who reported hearing impairment were 30% more likely to suffer from
      ET than were controls (odds ratio 1.3; 95% confidence interval 1.01-1.7; p =
      0.04). ET seemed to be associated with reported hearing impairment. The basis for
      this finding, which has been noted in several studies, deserves further
      exploration.

PMID- 18073495
TI  - Mortality in individuals with mild cognitive impairment. Results of the Leipzig
      Longitudinal Study of the Aged (LEILA75+).
AB  - OBJECTIVE: This study aimed to investigate whether mortality is higher for
      individuals suffering from Mild Cognitive Impairment (MCI). METHODS: A community
      sample of 1,045 dementia-free individuals aged 75 years and over was examined
      using neuropsychological tests over a 4.5-year period. Data were analyzed with
      the Cox proportional hazards model after having been adjusted for age, gender,
      and incident dementia. RESULTS: Association between MCI and mortality was
      examined subject to varied diagnostic criteria of MCI. We found an increased risk
      of death that was about 1.5 times higher for individuals with MCI when a
      cognitive performance of more than 1.5 standard deviation below the mean of age-
      and education-matched controls was required and the criterion of a cognitive
      complaint was excluded. Males were at about a 40% increased risk of death. Risk
      also increased with age by about 8% per year. Incident dementia showed a
      significant influence on mortality only if it became manifest by 1.5 years after
      the baseline measurement (follow-up 1). CONCLUSION: MCI is associated with
      increased mortality when certain diagnostic criteria are applied.

PMID- 18073496
TI  - Pain-related activation of leukocyte cellular adhesion molecules: preliminary
      findings.
AB  - BACKGROUND/AIMS: Acute adrenergic stressors have been found to activate
      neuroendocrine pathways that can alter leukocyte migration and activity.
      Leukocyte migration is known to affect the pathophysiology of inflammatory
      disease processes. This study examined the effects of acute experimental pain on
      catecholamine and cortisol levels and leukocyte expression of cellular adhesion
      molecules. METHODS: Healthy subjects (n = 10) underwent 45 min of acute
      experimental pain using earlobe electrical stimulation. Measures included sensory
      and affective pain responses, perceived stress, circulating levels of
      catecholamines, cortisol, and expression of integrin (CD11a+) cellular adhesion
      molecules on leukocyte subsets. Data were collected at baseline, after 22.5 and
      45 min of pain, and 180 min after pain cessation. RESULTS: Experimental pain
      acutely increased circulating levels of epinephrine, along with increases in the
      number of CD8+CD11a+ leukocytes and the density of CD11a molecules on CD8+ cells.
      Positive correlations were found between pain and stress scores, and the number
      of CD8+CD11a+ leukocytes. CONCLUSION: Acute pain induces elevated cellular
      adhesion molecule expression on leukocytes, which has possible implications for
      increasing leukocyte infiltration and disease exacerbation in patient populations
      with inflammatory syndromes.

PMID- 18073497
TI  - Stress/aggressiveness-induced immune changes are altered in adult rats submitted
      to neonatal malnutrition.
AB  - BACKGROUND/AIMS: Neonatal malnutrition induces metabolic and endocrine changes
      that have beneficial effects on the neonatal in the short term but, in the longer
      term, these alterations lead to maladaptations. We investigated the effect of
      neonatal malnutrition on immune responses in adult rats submitted or not to an
      aggressiveness test. METHODS: Male Wistar rats were distributed to one of two
      groups according to their mothers' diet during lactation: the well-nourished
      group (group C, n = 42, receiving 23% of protein) and the malnourished group
      (group MN, n = 42, receiving 8% of protein). After weaning, all rats received
      normoproteic diet. Ninety days after birth, each group was subdivided into three
      subgroups: control rats (n = 14, respectively), aggressive rats (n = 14,
      respectively) and rats receiving foot shock (FS; n = 14, respectively). Plasma
      corticosterone concentration was measured after FS sessions. Leukocyte counts and
      humoral immunity were evaluated. RESULTS: In neonatal malnourished animals, FS
      induced stress reduced plasma corticosterone concentration. Intraspecific
      aggressiveness induced alterations in leukocyte counts and antibody titers 7 and
      15 days after immunization. Neonatal malnourished animals showed no changes in
      the immune parameters evaluated. CONCLUSIONS: Expression of intraspecific
      aggressiveness activates the immune system. Neonatal malnutrition seems to have a
      long-lasting effect on components of both neuroendocrine and immune functions.

PMID- 18073498
TI  - Alexithymia and interleukin variations in somatoform disorder.
AB  - OBJECTIVE: The aim of the present study was to investigate if somatoform
      disorders (SFD) are associated with changes in the normal serum levels of
      important interleukins, and further, to establish if these changes are related to
      the presence and severity of alexithymia in patients with SFD. METHODS: Twenty
      four unmedicated patients who met the International Classification of Diseases
      (ICD-10) diagnostic criteria for SFD completed the psychological questionnaire to
      assess alexithymia (Toronto Alexithymia Scale), symptom reporting (SCL-90-R) and
      diagnostic criteria for SFD (Screening for Somatoform Symptoms scale). Serum
      concentrations of soluble interleukin 2 receptor alpha (sIL-2 Ralpha), IL-4, IL
      6, IL-10 and IL-12 were determined in patients with SFD and in 9 healthy
      subjects. RESULTS: In patients with SFD, serum levels of IL-6 (p < 0.001), IL-10
      (p = 0.047) and immunoglobulin E (p = 0.045) were significantly increased in
      comparison with healthy controls. Additionally, a negative correlation was
      observed between the level of alexithymia ('total' Toronto Alexithymia Scale
      score) and the serum levels of sIL-2 Ralpha (r = -0.538) in SFD. CONCLUSIONS:
      Taken together, these results suggest that SFD, with clinically significant
      alexithymia, are associated with a reduction in Th1-mediated immune function and
      an increase in the activation of the Th2 immune function, indicated by the
      augmented serum levels of IL-6 and IL-10 and elevated immunoglobulin E.

PMID- 18073499
TI  - Thyroid function changes and cytokine alterations following major surgery.
AB  - To establish whether cytokine release is implicated in thyroid hormone changes
      during surgical stress we studied 36 adult patients (20 men; mean age +/- SD:
      68.5 +/- 10.5 years) undergoing elective major abdominal operations. We measured
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8 and IL-10 and
      thyrotropin (TSH), free thyroxine (FT(4)) and triiodothyronine (T(3)) before
      scheduled non-emergency surgery, immediately postoperatively, on the 1st
      postoperative day (post-1) and on the 2nd postoperative day (post-2). TNF-alpha,
      IL-6 and IL-8 peaked on day post-1 whereas IL-10 peaked immediately
      postoperatively. Fourteen of 36 patients had low T(3) levels after surgery,
      indicating non-thyroidal illness (NTI). Significant negative correlations were
      noted among TNF-alpha, IL-6 and IL-8 against T(3) and FT(4). Cytokines are
      responsible, at least in part, for NTI following major operations.

PMID- 18073500
TI  - Disturbance of serum interleukin-2 and interleukin-8 levels in posttraumatic and
      non-posttraumatic stress disorder earthquake survivors in northern China.
AB  - OBJECTIVE: It is evident that immune cytokines are involved in the
      pathophysiology of posttraumatic stress disorder (PTSD), but results of different
      studies are still inconsistent. Here, serum interleukin (IL)-2, IL-6 and IL-8
      levels were compared between earthquake survivors with PTSD, those with non-PTSD
      and normal controls to investigate whether there is any relationship between
      cytokine levels and PTSD. In addition, the relationship of these cytokines with
      psychological parameters of the disorder was examined as well. METHODS: Thirty
      four earthquake survivors with PTSD (according to DSM-IV criteria), 30 earthquake
      survivors with non-PTSD and 34 controls were recruited in northern China using
      the Composite International Diagnostic Interview instrument. Serum IL-2, IL-6 and
      IL-8 levels were compared. IL-2 levels were measured by radioimmunometric assay,
      while serum IL-6 and IL-8 levels were measured using sandwich enzyme-linked
      immunosorbent assay. Psychological symptoms were assessed using 3 subscales of
      the Symptoms Checklist (SCL-90-R), including depression, anxiety and
      somatization. RESULTS: Only earthquake survivors diagnosed with PTSD had
      significantly lower serum IL-8 levels. Also, we found that earthquake survivors
      (either with PTSD or non-PTSD) had significantly lower serum IL-2 levels and more
      severe psychological symptoms. The severity of depressive and anxiety symptoms in
      earthquake survivors was positively related to serum IL-6 levels. CONCLUSIONS:
      PTSD may be associated with a reduced level of serum IL-8, and traumatic
      survivors may be associated with a lower level of serum IL-2.

PMID- 18073502
TI  - From Neuroendocrinology to Neuroimmunomodulation - a tribute to Prof. Dr. Samuel
      McCann.
AB  - One of the leading experts in the field of Neuroendocrinology and
      Neuroimmunmodulation, Samuel Mac Donald McCann, known by all his friends as
      'Don', passed away in 2007. This article pays tribute to his outstanding
      scientific contribution and a glimpse on his fascinating personality. A member of
      the National Academy of Sciences of the United States and pioneer in the field of
      neuroendocrine regulation, he identified numerous hormones and peptides and set
      the stage for basic concepts in physiology and clinical medicine.

PMID- 18073503
TI  - The immune-pineal axis: a shuttle between endocrine and paracrine melatonin
      sources.
AB  - The time course of the innate immunological response involves a pro-inflammatory
      phase followed by an anti-inflammatory phase. Pro-inflammatory responses serve as
      a defense against several stressor conditions, and sequential processes that shut
      down these responses are necessary to avoid exacerbation or the development of
      chronic diseases. In the present review, we put together recent data that show
      that the pineal gland is a player in bidirectional control of the inflammatory
      response. Healthy organisms stay in standby mode, ready to react. The nocturnal
      melatonin surge impairs the rolling and adherence of leukocytes to endothelial
      layers, limiting cell migration, and stimulates nocturnal production of IL-2 by T
      helper lymphocytes, exerting an immunostimulatory effect. Otherwise, the release
      of TNF-alpha from activated macrophages suppresses the nocturnal melatonin surge,
      allowing a full cell migration and inhibiting IL-2 production. In sequence,
      activated mononuclear and polymorphonuclear cells produce melatonin in a
      paracrine manner at the site of injury, which scavenges free radicals and
      collaborates to resolve the inflammatory response. The sequential diminution of
      TNF-alpha production is followed by the recovery of the nocturnal melatonin surge
      and IL-2 production. In summary, the immune-pineal axis, implicated in the
      sequential involvement of the melatonin produced by the pineal gland and immune
      competent cells, is an integral participant of the innate immune response.

PMID- 18073504
TI  - Vasoactive intestinal peptide regulates Th17 function in autoimmune inflammation.
AB  - An imbalance of pro-inflammatory and anti-inflammatory cytokines, autoreactive
      and inflammatory T helper 1 (Th1) cells, and regulatory T (Treg) cells results in
      the loss of immune tolerance and the subsequent appearance of inflammatory
      autoimmune diseases. On the other hand, hormones and neuropeptides are endogenous
      factors controlling the immune homeostasis that have been proposed as therapeutic
      agents in different autoimmune disorders. Among them, the vasoactive intestinal
      peptide (VIP) has been shown to downregulate the inflammatory response and to
      alter the Th1/Th2 balance in favor of anti-inflammatory Th2 immune responses.
      Recent studies have revealed a greater diversification of the T cell effector
      repertoire with the identification of Th17 cells. This subpopulation has been
      shown to be pathogenic in several autoimmune diseases previously attributed to
      the Th1 lineage. Arising new data and a critical revision of already published
      studies indicate that VIP is an immunomodulatory therapeutic agent targeting the
      Th17/Treg pathway.

PMID- 18073505
TI  - Analysis of the cerebral transcriptome in mice subjected to traumatic brain
      injury: importance of IL-6.
AB  - Traumatic brain injury is one of the leading causes of incapacity and death among
      young people. Injury to the brain elicits a potent inflammatory response,
      comprising recruitment of inflammatory cells, reactive astrogliosis and
      activation of brain macrophages. Under the influence of presumably several
      cytokines and growth factors, a cascade of events is activated that result
      ultimately in increased oxidative stress and tissue damage, but also in
      activation of counterregulatory factors and tissue regeneration. The complexity
      of this response is being unraveled by high-throughput methodologies such as
      microarrays. The combination of these modern techniques with the comparison of
      normal and genetically modified mice boosts the significance of the results
      obtained. With this approach, we have demonstrated that a cytokine such as
      interleukin-6 is one of the key players in the response of the brain to injury.

PMID- 18073506
TI  - Matrix metalloproteinase-9 is involved in the development and plasticity of
      retinotectal projections in rats.
AB  - OBJECTIVE: During postnatal development, retinotectal projections undergo a
      process of misplaced axon elimination, leading to a topographical matching
      between the retinal surface and the superior colliculus. Matrix
      metalloproteinases (MMPs) have been implicated in the development and plasticity
      of the nervous system. We studied the expression and role of MMPs during normal
      development of retinotectal projections and after monocular enucleation-induced
      plasticity. MATERIAL AND METHODS: Lister hooded rats at different postnatal ages
      received subpial ethylene vinyl acetate 40W implants to deliver an MMP inhibitor
      or vehicle to the superior colliculus. Animals received intraocular injections of
      horseradish peroxidase for anterograde tracing of ipsilateral projections. For
      immunoblotting and zymography, colliculi were removed without fixation. RESULTS:
      We observed the highest MMP activity in the first postnatal week, with decreasing
      activity thereafter. Monocular enucleation at postnatal day 10 yielded a rapid
      increase in MMP activity, 24 h following denervation of the contralateral
      colliculus. Importantly, inhibition of MMP activity in vivo induced a marked
      delay of axonal clustering along the medial aspect of colliculus. CONCLUSIONS:
      Our data indicate that MMPs are crucial in retinotectal development concurring to
      the fine tuning of topographical order and synaptic specificity of these
      connections.

PMID- 18073507
TI  - Central blockade of IL-1 does not impair taste-LPS associative learning.
AB  - After saccharin intake is associated with the consequences of peripheral
      lipopolysaccharide (LPS) administration, rats develop a strong conditioned
      avoidance behavior against this gustatory stimulus. To investigate the role of
      central interleukin-1 (IL-1) as a key signal during taste-LPS engram formation,
      rats were chronically infused with IL-1 receptor antagonist into the lateral
      ventricle of the brain before, during and after a single association trial. The
      results indicate that a stable taste-LPS engram can be formed even under the
      chronic blockade of central IL-1 signaling during engram formation and
      consolidation. More importantly, our data show that animals which did not
      experience a fever response during association phase (due to the LPS encounter)
      were unable to elicit hyperthermia as part of the conditioned response. These
      data indicate that pairing a relevant taste stimulus with an immune challenge,
      such as LPS, might result in the formation of multiple engrams, specifically
      codifying independent information.

PMID- 18073508
TI  - A model of premature aging in mice based on altered stress-related behavioral
      response and immunosenescence.
AB  - The intensity of behavioral and neuroendocrine responses to stressful stimuli in
      rodent strains seems to be inversely related to their life span. We have
      previously shown that interindividual differences in members of outbred Swiss and
      inbred BALB/c mouse populations, both male and female, may be related to their
      behavior in a simple T-maze test. The animals that explore the maze slowly show
      impaired neuromuscular vigor and coordination, decreased locomotor activity,
      increased level of emotionality/anxiety, decreased levels of brain biogenic
      amines as well as immunosenescence and decreased life span, when compared to
      their control counterparts, which quickly explore the maze. These traits are
      similar to some of the alterations previously observed in aging animals and
      therefore we proposed that those 'slow mice' are biologically older than the fast
      animals and may be a model of prematurely aging mice (PAM). Although most of our
      work on this model has been performed on chronologically adult-mature animals, we
      have also shown that certain characteristics of PAM, such as increased anxiety
      and deficient immune response, are already present in chronologically young
      animals. Thus, it is tempting to hypothesize that chronic hyperreactivity to
      stress (trait anxiety) leading to immune dysfunction may have a causal
      relationship with impaired health and premature aging. In view of the link
      between oxidative stress and the aging process, the redox state of peritoneal
      leukocytes from PAM has been studied, showing an oxidative stress situation. In
      the present work we have determined the levels of a key antioxidant, reduced
      glutathione (GSH), and the oxidant malondialdehyde (MDA), a marker of lipid
      peroxidation, both in the spleen and brain of male and female PAM and non-PAM
      (NPAM). We found that GSH and MDA are decreased and increased, respectively, in
      PAM with respect to NPAM. Moreover, diet supplementation with antioxidants showed
      to be an effective strategy for protection against early immune and behavioral
      decline, altered redox state of leukocytes and premature mortality in PAM, which
      supports the validity of this model of premature aging as well as its link with
      oxidative stress.

PMID- 18073509
TI  - Plasma aminothiol compounds, but not serum tumor necrosis factor receptor II and
      soluble receptor for advanced glycation end products, are related to the
      cognitive impairment in Alzheimer's disease and mild cognitive impairment
      patients.
AB  - Increasing evidence indicates that factors such as oxidative stress, plasma
      homocysteine increase and glutathione depletion, elevated pro-inflammatory
      cytokines and advanced glycation end products can play a role in Alzheimer's
      disease (AD) pathogenesis. The receptor for advanced glycation end products
      (RAGE) is a cell surface receptor that has been implicated in neurodegeneration,
      and a soluble isoform of RAGE (sRAGE) has the ability to prevent the adverse
      effects of RAGE signaling by acting as a decoy. Twenty-five patients with AD, 26
      with mild cognitive impairment (MCI) and 44 age-matched control subjects were
      studied. All subjects were classified according to their clinical, cognitive and
      positron emission tomography study. Serum levels of sRAGE and TNF-alpha receptor
      II were not significantly different in AD or MCI patients compared to controls.
      Total plasma levels of glutathione and its metabolite cysteinglycine were
      decreased in AD and MCI patients compared to the control group. In addition, AD
      patients presented significantly increased plasma homocysteine compared to those
      in MCI patients and controls. We found significant positive correlations between
      sRAGE and glutathione, cysteinglycine and cysteine levels. Moreover, a
      significant negative correlation between the total score of cognitive impairment
      and homocysteine levels, and significant positive correlations with glutathione,
      cysteinglycine and cysteine levels were observed. These findings indicate that
      plasma aminothiol compounds are associated with AD and MCI patients and with
      their cognitive status.

PMID- 18073510
TI  - Modulation by astrocytes of microglial cell-mediated neuroinflammation: effect on
      the activation of microglial signaling pathways.
AB  - The strong inflammatory response observed in neurodegenerative diseases can
      depend on the impairment of the endogenous control of microglial activation,
      triggering the release of potentially detrimental factors such as cytokines,
      nitric oxide (NO) and superoxide anion (O(2)(-)). Our aim was to study the
      activation of microglial cells and the transduction pathways involved in their
      modulation by IL-1beta and TNF-alpha. Microglial and mixed glial cell cultures
      from neonatal rats were exposed to IFN-gamma and/or IL-1beta and TNF-alpha. We
      analyzed NO secretion and the activation of ERK and STAT1. We found that
      astrocytes modulated microglial cell activation, decreasing production of NO. IFN
      gamma induced an 18- to 25-fold increase in NO, associated to a 3- to 5-fold
      increase in ERK phosphorylation in microglial cultures. IL-1beta, but not TNF
      alpha, inhibited IFN-gamma-induced production of NO in microglia by 87%. It also
      reduced IFN-gamma-induced phosphoERK (pERK) by 40%, without affecting
      phosphoSTAT1 (pSTAT1). In contrast, in microglial cultures exposed to media
      conditioned by astrocytes, IL-1beta did not inhibit pERK, whereas it reduced
      activation of STAT1. Inducible NO synthase expression induced by IFN-gamma in
      microglial cultures was reduced when the activation of ERK was prevented. We
      propose that IL-1beta modulates IFN-gamma-induced production of oxidative
      molecules through cross talk between STAT1 and MAPK pathways, regulating the
      amplitude and duration of microglial activation. Modulation of ERK was observed
      at 30 min, whereas inhibition of pSTAT was observed later (at 4 h), indicating
      that it was an early and transient phenomenon.

PMID- 18073511
TI  - NOD mice exocrinopathy: towards a neuroimmune link.
AB  - Sjogren's syndrome (SS) is a chronic autoimmune disorder of exocrine glands
      characterized as an autoimmune exocrinopathy and more specifically as an
      autoimmune epithelitis. An impaired balance of neuroimmune interactions mediated
      by vasoactive intestinal peptide (VIP) in the target organ at early stages of
      disease is explored by means of the nonobese diabetic (NOD) mouse model of SS. We
      have previously described a reduced salivary secretion and signaling upon VIP
      stimulation. The effect reflected a differential regulation of the neural isoform
      of nitric oxide synthase by calcium calmodulin kinase II and occurred prior to
      the appearance of detectable levels of cytokines in NOD glands. VIP acting on NOD
      macrophages treated with lipopolysaccharide promoted anti-inflammatory effects by
      inhibiting nitric oxide synthase induction as well as IL-12 and TNF-alpha
      production, while stimulating IL-10. Here we present evidence on the ability of
      apoptotic acinar cells from submandibular glands of NOD mice to stimulate nitric
      oxide in both peritoneal and glandular macrophage pools to a similar extent as
      lipopolysaccharide + IFN-gamma. VIP was not effective to prevent nitrite
      accumulation and modestly increased IL-10 levels in macrophages coincubated with
      acinar cells. An enhanced nitrite response of NOD glandular macrophages in basal
      and stimulated conditions compared to peritoneal cells is also shown.

PMID- 18073512
TI  - Cannabinoid system and neuroinflammation: implications for multiple sclerosis.
AB  - There is a growing amount of evidence suggesting that cannabinoids may be
      neuroprotective in central nervous system inflammatory conditions. Advances in
      the understanding of the physiology and pharmacology of the cannabinoid system
      have potentiated the interest in cannabinoids as potential therapeutic targets.
      Here our aim was to update the actions of cannabinoids on immune system and glial
      cells and their implications on multiple sclerosis. We also show our results on
      the modulation of cytokines of the IL-12 family by cannabinoids in macrophages
      and brain microglia. We used murine primary cultures of macrophage and microglia
      activated by lipopolysaccharide/IFN-gamma and Theiler's virus to study the
      effects of cannabinoids on the regulation of IL-12 and IL-23 mRNA and protein IL
      12p40, evaluated by RT-PCR and ELISA, respectively. Cannabinoids negatively
      regulate the production of these cytokines by microglial cells in part due to the
      activation of CB(2) receptors. The effects of cannabinoids on cytokine brain work
      and on the regulation of neuroinflammatory processes may affect chronic
      inflammatory demyelinating diseases such as multiple sclerosis.

PMID- 18073513
TI  - Endocannabinoids in TNF-alpha and ethanol actions.
AB  - During marijuana and alcohol consumption as well as during inflammation the
      reproductive axis is inhibited, mainly through the inhibition of luteinizing
      hormone-releasing hormone release. In male rats, this inhibitory effect is
      mediated, at least in part, by the activation of hypothalamic cannabinoid type 1
      receptors (CB1). During inflammation, this activation of the endocannabinoid
      system seems to be mediated by an increase in TNF-alpha production followed by
      anandamide augmentations, similarly the effect of intragastric administration of
      ethanol (3 g/kg) seems to be due to an increase in anandamide. On the other hand,
      a number of different actions mediated by the endocannabinoid system in various
      organs and tissues have been described. Both cannabinoid receptors, CB1 and CB2,
      are localized in the submandibular gland where they mediate the inhibitory effect
      of intrasubmandibular injections of the endocannabinoid anandamide (6 x 10(-5)M)
      on salivary secretion. Lipopolysaccharide (5 mg/kg/3 h) injected
      intraperitoneally and ethanol (3 g/kg/1 h) injected intragastrically inhibited
      the salivary secretion induced by the sialogogue metacholine; this inhibitory
      effect was blocked by CB1 and/or CB2 receptor antagonists. Similar to the
      hypothalamus, these effects seem to be mediated by increased anandamide. In
      summary, similar mechanisms mediate the inhibitory actions of endocannabinoids
      and cannabinoids in both hypothalamus and submandibular gland during drug
      consumption and inflammation.

PMID- 18073514
TI  - Impaired immune responses in tuberculosis patients are related to weight loss
      that coexists with an immunoendocrine imbalance.
AB  - The study's objective was to examine whether factors related to the host status
      may bear some relation with the profile of the immune response displayed by
      tuberculosis (TB) patients. The in vitro immune response (antigen-driven
      lymphoproliferation and cytokine production) and the presence of alcoholism or
      disease-related factors, like heart and respiratory rates, and weight loss (body
      mass index, BMI) were investigated in 31 males with active, untreated TB.
      Compared to 16 age-matched healthy males, TB patients presented depressed
      lymphoproliferation and increased IL-10 and TGF-beta production. Multivariate
      analysis indicated that most differences were no longer significant when
      controlling for the BMI. Immune and endocrine changes coexisting with weight
      loss, such as circulating levels of TNF-alpha, IFN-gamma, IL-6, cortisol,
      dehydroepiandrosterone and thyroid hormones, were also analyzed. While pairwise
      correlations between serum levels of IFN-gamma, T3 or T4 and BMI were not
      significant, BMI was negatively correlated with IL-6 levels (p < 0.025). In turn,
      levels of IL-6 correlated positively with cortisol concentrations (p <0.001).
      Stepwise regression analysis demonstrated that BMI was only associated with IL-6
      (r = -0.423, R(2) = 0.18), with the difference remaining significant following
      adjustment for the other variables. As regards IL-6, BMI, cortisol and IFN-gamma
      could explain 74% of variability in IL-6 concentrations (R(2) = 0.74). No
      evidence for effect modification was shown when performing adjusted calculations.
      To conclude, the relation between weight loss and abnormal immune response of TB
      patients is partly associated with the immunoendocrine imbalance observed in
      parallel.

PMID- 18073515
TI  - Effects of moderate consumption of distilled and fermented alcohol on some
      aspects of neuroimmunomodulation.
AB  - Alcoholic beverages are characterized by their fermented versus distilled origin
      and also by their degree of alcohol. The toxic effects of chronic alcohol
      consumption have been widely studied. However, there is less evidence about
      possible beneficial effects of moderate alcohol intake. This work was aimed at
      evaluating the effects of moderate alcohol consumption (beer or ethanol) on
      plasma hormone concentrations, blood and thymus lymphocyte phenotypes and brain
      neurotransmitter levels. For this purpose, 40 adult Wistar male rats were
      administered ethanol or beer for 4 weeks (experimental groups). Age-matched rats
      were administered beer without alcohol or water to be used as controls. Rats were
      killed by decapitation and plasma from the trunk blood was collected to measure
      plasma prolactin, growth hormone and ACTH concentrations by homologous specific
      double antibody radioimmunoassays. Thymus and blood lymphocyte subsets were
      measured by flow cytometry. Neurotransmitter concentrations [dopamine, gamma
      aminobutyric acid (GABA) and taurine] were measured by high pressure liquid
      chromatography in the median eminence and the pituitary. Blood and thymus
      lymphocyte subsets were not significantly changed by either ethanol or beer
      consumption, compared to controls. Plasma prolactin levels significantly
      decreased in ethanol-administered groups (p < 0.05) compared to control animals
      drinking water, although plasma levels of growth hormone and ACTH were not
      modified by either alcohol used. Dopamine and GABA concentrations in the median
      eminence or in the adenohypophysis remained unmodified by moderate beer or
      ethanol consumption. However, taurine concentration was significantly increased
      in the pituitary (p < 0.05) in the group drinking ethanol compared to those
      groups drinking beer with or without alcohol. These data suggest that moderate
      alcohol consumption may change the regulatory mechanism of prolactin secretion.
      Whether these modifications have a physiological significance deserves further
      research.

PMID- 18073516
TI  - Neuroimmunomodulation during exercise: role of catecholamines as 'stress
      mediator' and/or 'danger signal' for the innate immune response.
AB  - Exercise-induced neuroimmunomodulation is clearly accepted today. The present
      article reviews the main literature concerning the immunomodulatory capacity of
      catecholamines on the innate immune response during physical exercise, and
      presents our laboratory's latest results on this topic. It is well known that the
      effects of exercise on the immune system are mediated by the 'stress hormones and
      mediators'. Although catecholamines have usually been regarded as
      immunosuppressors, they may stimulate innate immune response mechanisms (such as
      phagocytic function) during exercise-induced stress, even without previous
      antigenic stimulation. The exercise-induced stimulation of the phagocytic
      response in particular and the innate responses in general have been considered
      as a prevention strategy of the athlete's organism in order to prevent the entry
      and/or maintenance of antigens in a situation where the adaptive immune response
      seems to be depressed, and thus it has been suggested that catecholamines
      participate as a 'stress mediator' of these effects. Given this hypothesis, it is
      also suggested here that catecholamines may be the first 'danger signal' to the
      immune system during exercise-induced stress.

PMID- 18073517
TI  - Is there a role for cellular prion protein in intrathymic T cell differentiation
      and migration?
AB  - The cellular prion protein (PrP(C)) is expressed in the nervous and immune
      systems. Functionally, PrP(C) has been suggested to participate in neuron
      survival, neuritogenesis and T lymphocyte activation. Moreover, PrP(C)
      interaction with laminin influences neuronal adhesion and neurite extension.
      Nevertheless, so far the physiological role of PrP(C) has not been completely
      elucidated, particularly in the immune system. The aim of the study was to
      evaluate the possible participation of PrP(C) in intrathymic T cell development.
      We evaluated T cell differentiation markers in thymocytes and peripheral
      lymphocytes, as well as thymocyte death in PrP(C)-null or PrP(C)-overexpressing
      (Tga20) mice, compared to wild-type controls. In these same animals, we
      ascertained laminin-driven thymocyte migration. Compared to controls, only
      marginal differences were found in PrP(C)-null animals. However, Tga20 mice
      exhibited a severe thymic hypoplasia, with 10-20% lymphocytes compared to wild
      type counterparts. In particular, the frequency of CD4+CD8+ cells was largely
      reduced, and this was accompanied by a dramatic increase in the frequency of CD4
      CD8- thymocytes, which could be as high as 60-65% of the whole-cell suspensions.
      Moreover, Tga20 mice exhibited an increase in thymocyte death, comprising the
      CD4+CD8+, as well as CD4+ and CD8+ single-positive cells. Additionally, laminin
      driven migration was largely impaired in Tga20 mice, in which we also found a
      significant decrease in total T lymphocytes in the spleen and lymph nodes. Our
      results show that PrP(C) overexpression alters intrathymic T cell development, a
      defect that likely has a negative impact in the formation of the T cell
      peripheral pool.

PMID- 18073518
TI  - Targeted spinal cord therapeutics delivery: stabilized platform and
      microelectrode recording guidance validation.
AB  - BACKGROUND/AIMS: No validated delivery technique exists for accurate,
      reproducible delivery of biological therapies to discrete spinal cord targets. To
      address this unmet need, we have constructed a stabilized platform capable of
      supporting physiologic mapping, through microelectrode recording, and cellular or
      viral payload delivery to the ventral horn. METHODS: A porcine animal model (n =
      7) has been chosen based upon the inherent morphologic similarities between the
      human and porcine spine. Animals underwent physiologic mapping and subsequent
      microinjection of a green-fluorescent-protein-labeled cell suspension. Sacrifice
      (t = 3 h) was performed immediately following behavioral assessment. RESULTS:
      Histologic analysis has supported our ability to achieve localization to the
      ipsilateral ventral horn in the spinal cord. Complications included death due to
      malignant hyperthermia (n = 1), hindlimb dysfunction attributable to epidural
      hematoma (n = 1), and hindlimb dysfunction attributable to cord penetration (n =
      2). CONCLUSIONS: These results indicate an ability to achieve accurate targeting,
      but the elevated incidence of neurologic morbidity will require further studies
      with longer follow-ups that incorporate procedural and equipment modifications
      that will allow for a reduced number of cord penetrations and will account for
      observed cardiorespiratory-associated cord movement. These initial results
      reinforce the challenges of translating biological restorative therapies from
      small to large animal models and ultimately to humans.

PMID- 18073519
TI  - Intracranial hypotension from intrathecal baclofen pump insertion. A case report
      and review of the literature.
AB  - Intracranial hypotension is a syndrome of low cerebrospinal fluid pressure with a
      variable clinical presentation ranging from postural headaches to coma. A number
      of neuroradiologic techniques are now available to aid in the diagnosis of this
      syndrome (CT, MRI, radioisotope cisternography and CT myelography), each showing
      specific radiographic abnormalities. In this report, we present a case of
      intracranial hypotension secondary to baclofen pump placement. We review the
      major clinical findings, neuroimaging abnormalities, key diagnostic features as
      well as treatment options.

PMID- 18073520
TI  - Successful bilateral subthalamic nucleus stimulation for segmental dystonia after
      unilateral pallidotomy.
AB  - BACKGROUND: Several subcortical structures have been targeted for surgical
      treatment of dystonia, including motor thalamus, internal segment of globus
      pallidus (GPi), and more recently, the subthalamic nucleus (STN). Deep brain
      stimulation of GPi is currently the preferred surgical treatment, but it is
      unclear if targeting other structures would yield better results. Patients who
      have already had a pallidotomy yet continue to experience dystonic symptoms may
      be limited in further treatment options. METHODS: A patient with medically
      intractable, segmental, early-onset, primary torsion dystonia presented for
      surgical consultation after exhausting nearly all treatment options. Medications,
      botulinum toxin injections, cervical denervation surgery, and left-sided
      pallidotomy failed to give adequate relief. The patient was implanted with STN
      stimulating leads bilaterally according to standard procedures. RESULTS: The
      patient received a 36% improvement in dystonic symptoms as measured by several
      dystonia rating scales. These benefits persisted for 2 years after surgery
      despite several hardware-related complications, and the patient reported being
      very satisfied with the outcome. CONCLUSION: This result supports the efficacy of
      STN deep brain stimulation in dystonia patients, even those with prior
      pallidotomy.

PMID- 18073521
TI  - Microelectrode-guided deep brain stimulation for Tourette syndrome: within
      subject comparison of different stimulation sites.
AB  - BACKGROUND: As medical therapy for Tourette syndrome (TS) is ineffective in a
      small subset of patients, surgical interventions, including deep brain
      stimulation at various sites, have been developed in recent years. CASE
      DESCRIPTION: We present the case of a 40-year-old woman with TS whose severe tics
      had caused unilateral blindness. Despite trials of more than 40 medications, her
      symptoms improved significantly only after placement of bilateral deep brain
      stimulators in the anterior inferior internal capsule. However, symptomatic
      improvement was not complete, and her electrode connections eventually became
      permanently damaged by the remaining retrocollic jerks. She underwent removal of
      the internal capsule electrodes and placement of centromedian nucleus thalamic
      stimulators with significantly improved tic control. CONCLUSION: Whereas the
      anterior internal capsule site had also produced psychiatric side effects such as
      altered mood and impulse control, the thalamic site has not done so to date.
      Thus, distinct surgical targets for TS may be appropriate for patients with
      specific comorbidities.

PMID- 18073522
TI  - Magnetic resonance imaging of implanted deep brain stimulators: experience in a
      large series.
AB  - Magnetic resonance imaging (MRI) is a commonly used and important imaging
      modality to evaluate lead location and rule out complications after deep brain
      stimulation (DBS) surgery. Recent safety concerns have prompted new safety
      recommendations for the use of MRI in these patients, including a new
      recommendation to limit the specific absorption rate (SAR) of the MRI sequences
      used to less than 0.1 W/kg. Following SAR recommendations in real-world
      situations is problematic for a variety of reasons. We review our experience
      scanning patients with implanted DBS systems over a 7-year period using a variety
      of scanning techniques and four scanning platforms. 405 patients with 746
      implanted DBS systems were imaged using 1.5-tesla MRI with an SAR of up to 3
      W/kg. Many of the DBS systems were imaged multiple times, for a total of 1,071
      MRI events in this group of patients with no adverse events. This series strongly
      suggests that the 0.1 W/kg recommendation for SAR may be unnecessarily low for
      the prevention of MRI-related adverse events.

PMID- 18073523
TI  - Catheter placement for Ommaya reservoirs with frameless surgical navigation:
      technical note.
AB  - OBJECTIVE: Infusion of intraventricular chemotherapy requires precise ventricular
      catheter placement in oncology patients to avoid intraparenchymal infusion. We
      assessed the safety and precision of using frameless surgical navigation for the
      placement of Ommaya reservoir catheters. METHODS: In 20 consecutive patients who
      required Ommaya reservoirs for the administration of intrathecal chemotherapy,
      the catheters were positioned with the guidance of frameless stereotaxy.
      Precision of catheter placement, operative time, operative complications, and
      postoperative complications were assessed. RESULTS: All catheters were completely
      within cerebrospinal fluid and 90% were within 5 mm of the intended target, the
      ipsilateral foramen of Monro. The average operative time was 47 min, and there
      were no intraoperative complications. There were no reports of
      leukoencephalopathy, and 3 patients had minor delayed complications. CONCLUSION:
      Frameless surgical navigation is a useful and efficient method for ensuring
      accurate catheter placement during Ommaya reservoir implantation, and it reduces
      the risk of potential parenchymal toxicity.

PMID- 18073524
TI  - Upregulation of stress-response genes with cell cycle arrest induced by carbon
      ion irradiation in multiple murine tumors models.
AB  - OBJECTIVE: To elucidate the in vivo biological effects induced by carbon-ion
      irradiation using comprehensive expression analysis. RESULTS: In all tumors, the
      level of expression of several tens of genes, including Ccl3, Ccng1, Cd80,
      Cdkn1a, Cxcl2, IL7r, Lrdd, Mgmt, Mmp8 and Polk, was significantly altered 6 h and
      day 1 following C-ion irradiation. At day 3, several hundred genes, many of which
      are also classified as stress-response or cell-communication genes, including
      Tnfrsf5, Ikbke and Icam1, were upregulated following C-ion irradiation. The
      expression level of the majority of these genes was similar following gamma-ray
      treatment, although the change was not as extensive and intertumor variance was
      apparent. Several genes, including Ikbke, Serpina3n and Saa3, responded
      differentially following C-ion irradiation than after gamma-ray irradiation.
      Pathological investigation and immunohistochemical analysis of Cdkn1a revealed
      cell cycle arrest with mitotic catastrophe in tumors irradiated by C-ions.
      MATERIALS AND METHODS: We examined gene expression changes after carbon-ion (C
      ion) irradiation (290 MeV/m, SOBP 6 cm middle, 50 kev/microm) with a single dose
      of 30 Gy in four mouse tumors (NR-S1, SCCVII, NFSa and #8520) transplanted into
      the hind legs of C3H/HeNrs mice, using 44K single-color oligo-microarrays at six
      hours (h), one day and three days after irradiation. Gamma rays of 30 Gy and 50
      Gy were used as a reference beam. Identification of C-ion-responsive genes was
      based on a false discovery rate of <5% using the Wilcoxon test (p < 0.001) and
      the Benjamini-Hochberg correction. CONCLUSIONS: This study revealed significant C
      ion induced upregulation of stress-responsive and cell-communication genes common
      to different tumor types. These findings provide evidence for the efficacy of
      this modality for the treatment of local tumors.

PMID- 18073525
TI  - Intratumor injection of oncolytic adenovirus expressing HSP70 prolonged survival
      in melanoma B16 bearing mice by enhanced immune response.
AB  - Heat shock proteins (HSPs) possess potent antitumor ability to stimulate immune
      response. We postulated that intratumor injection of oncolytic adenovirus over
      expressing HSPs might be able to exert antitumor activity by inducing antitumor
      immune response in immunocompetent hosts in addition to the oncolytic activity.
      In this study, two recombinant oncolytic adenoviruses, Ad.CMV.HSP.IRES.E1a and
      Ad.CMV.IRES.E1a, were constructed with or without the HSP expression cassette.
      The HSP expression and cytopathic killing effect in mouse B16 melanoma and human
      PLC/PRF/5 hepatoma cells were measured after in vitro infection of adenoviruses.
      Survival rate of immunocompetent C57/BL mice was observed following intratumor
      injection of recombinant adenoviruses in B16 melanoma xenograft models. To detect
      the evidence of immune responses, hematoxylin and eosin staining and RT-PCR for
      IFN-gamma expression in tumor tissues were performed. The Ad.CMV.HSP.IRES.E1a
      induced significantly higher HSP expression level than Ad.CMV.IRES.E1a in both
      B16 and PLC/ PRF/5 cells. The cytocidal efficacy of Ad.CMV.HSP.IRES.E1a and
      Ad.CMV.IRES.E1a in PLC/PRF/5 cells was much higher than that in B16 cells, where
      the two adenoviruses showed similarly very weak oncolytic effect in vitro.
      However, Ad.CMV.HSP.IRES. E1a improved animal survival rate and exhibited more
      potent anti-tumor efficiency than Ad.CMV.IRES.E1a in B16 xenograft models. The
      enhanced efficacy might be mainly attributed to the HSP-mediated immune activity,
      as evidenced by the up-regulated expression of IFN-gamma and local heavier
      intratumor inflammatory cell infiltration. These results indicated that the
      recombinant oncolytic adenovirus over-expressing HSPs possessed powerful in vivo
      anti-tumor efficacy and might be a valuable approach for cancer immune gene
      therapy.

PMID- 18073526
TI  - Cytostatic and cytotoxic properties of Amphinase: a novel cytotoxic ribonuclease
      from Rana pipiens oocytes.
AB  - Onconase (Onc), is a novel amphibian cytotoxic ribonuclease with antitumor
      activity, and is currently in a confirmatory phase III clinical trial for the
      treatment of malignant mesothelioma. It was recently reported that Rana pipiens
      oocytes contain still another ribonuclease, named Amphinase (Amph). Amph shows 38
      40% amino acid sequence identity with onconase, presents as four variants varying
      between themselves from 87-99% in amino acid sequence identity and has a
      molecular mass approximately 13,000. In the present study we describe the effects
      of Amph on growth of several tumor cell lines. All four variants demonstrated
      cytostatic and cytotoxic activity against human promyelocytic HL-60-, Jurkat T
      cell- and U-937 monocytic leukemia cells. The pattern of Amph activity to certain
      extent resembled that of Onc. Thus, cell proliferation was suppressed at 0.5-10.0
      mug/ml (40-80 nM) Amph concentration with distinct accumulation of cells in G(1)
      phase of the cell cycle. In addition, the cells were undergoing apoptosis, which
      manifested by DNA fragmentation (presence of "sub-G1" cells, TUNEL-positivity),
      caspases and serine proteases activation as well as activation of
      transglutaminase. The cytostatic and cytotoxic effects of Amph required its
      ribonuclease activity: the enzymatically inactive Amph-2 having histidine at the
      active site alkylated was ineffective. The effectiveness and cell cycle
      specificity was generally similar for all four Amph variants and at the equimolar
      concentrations was somewhat more pronounced than that of Onc. The observed
      cytostatic and cytotoxic activity of Amph against tumor cell lines suggests that
      similar to Onc this cytotoxic ribonuclease may have antitumor activity and find
      an application in clinical oncology.

PMID- 18073527
TI  - Staurosporine sensitizes T lymphoma cells to glucocorticoid-induced apoptosis:
      role of Nur77 and Bcl-2.
AB  - Glucocorticoids (GCs) are used for treatment of various hematopoietic
      malignancies owing to their ability to induce apoptosis. A major obstacle in
      leukemia therapy is the emergence of GC-resistant cells. Hence, combinatory
      treatment protocols should be developed that convert GC-resistant leukemia cells
      into sensitive ones. Here we demonstrate that the broad-acting kinase inhibitor
      staurosporine (STS) confers GC-sensitivity on GC-resistant T lymphoma cells
      expressing elevated levels of either Bcl-2 or Bcl-XL, but not on GC-resistant
      myelogenic leukemia cells expressing Mcl-1 in addition to Bcl-2 and/or Bcl-XL. In
      T lymphoma cells, STS induces the expression of the pro-apoptotic orphan receptor
      Nur77 that overcomes the anti-apoptotic effect of Bcl-2, thus enabling GCinduced
      apoptosis. However, in the myelogenic leukemia cells, STS does not upregulate
      Nur77. In these cells, the glucocorticoid receptor (GR) is rapidly downregulated
      by GC and the anti-apoptotic Mcl-1 protein is upregulated by STS, thereby leading
      to an even more resistant phenotype. Altogether, our data provide a molecular
      basis for the differential apoptotic response of T lymphoma versus myelogenic
      leukemia cells to STS and GC. The former being sensitized to GC-induced apoptosis
      by STS, whereas in the latter, STS intensifies GC resistance. The cell type
      specific responses should be taken into consideration when combinatory therapy is
      used for treating hematopoietic malignancies.

PMID- 18073528
TI  - High NaCl promotes cellular senescence.
AB  - High extracellular NaCl was previously shown to increase the number of DNA breaks
      in mammalian cells in tissue culture, renal medullary cells in vivo, C. elegans
      and marine invertebrates. It was also shown to increase reactive oxygen species
      in renal cells, resulting in oxidation of proteins and DNA. Cellular senescence
      is a common response to such damage. Therefore, in the present studies we looked
      for signs of senescence in cells exposed to high NaCl. We find that (1) the rate
      of proliferation of HeLa cells exposed to high NaCl decreases gradually to the
      point of arrest, and the cells display signs of senescence, including hypertrophy
      and increased auto fluorescence. (2) High NaCl accelerates the appearance of
      senescence in primary mouse embryonic fibroblasts, as measured by senescence
      associated beta-galactosidase activity (SA-beta-gal). (3) High NaCl retards
      growth and markedly decreases the life span of C. elegans, accompanied by
      features of accelerated aging, such as decreased locomotion and increased number
      of SA-beta-gal positive cells. (4) Mouse renal medullary cells, which are
      normally continuously exposed to high NaCl, express increased p16(INK4) (another
      indicator of senescence) much earlier than do cells in the renal cortex, which
      has the same level of NaCl as peripheral blood. We conclude that high NaCl
      accelerates cellular senescence and aging, most likely secondary to the DNA
      breaks and oxidative damage that it causes.

PMID- 18073529
TI  - All roads lead to mTOR: integrating inflammation and tumor angiogenesis.
AB  - Mammalian target of rapamycin (mTOR) is a crucial molecule in the control of cell
      size and proliferation; dysregulation of the mTOR pathway is commonly found in
      human cancers. Many cancer-promoting kinases have been identified as regulators
      of mTOR activity through phosphorylation and inactivation of the TSC1-TSC2
      complex. Tumorassociated macrophages (TAMs) are tumor-promoting factors in
      inflammation-mediated tumor development, and the signaling molecules involved in
      TAMs-mediated tumor angiogenesis are not well understood. Therefore, it is urgent
      to elucidate the cross-talk between inflammatory cells and cancers and to explore
      the precise pathways involved in TAMsinduced tumor angiogenesis. Recently IKKbeta
      was found to activate the mTOR pathway and to promote tumor angiogenesis through
      inactivation of the TSC1-TSC2 complex by phosphorylating TSC1. This finding
      provides critical insights into and suggests one mechanism behind inflammation
      mediated tumor angiogenesis. In this extra-view, we briefly discuss the possible
      influence of TAMs-released proangiogenic factors on mTOR activation and propose a
      model of the cross-talk between tumors and TAMs in tumor angiogenesis.

PMID- 18073530
TI  - Does caspase inhibition promote clonogenic tumor growth?
AB  - Defects in the control of cell death are a major cause of resistance to tumor
      therapy. Until recently, components of the intrinsic apoptotic pathway that act
      downstream of mitochondria, such as the caspases, have been apportioned only a
      minor share in this business. Thus, defects in mitochondrial caspase activation
      were suggested to cause apoptosis inhibition but not to confer clonogenic
      survival. This assumption was based on the finding that chemotherapeutic agents
      provoke mitochondrial damage even in the absence of caspases, resulting in the
      release of various toxic mediators and a subsequent caspase-independent cell
      death. In contrast to these earlier observations, we recently showed that in the
      absence of active caspases tumor cells do not necessarily undergo caspase
      independent cell death but may even survive a chemotherapeutic insult. Our
      findings suggest that caspase inhibition can indeed promote clonogenic tumor
      growth which might be not only relevant for tumor therapy but should be also
      considered when evaluating the safety of therapeutic caspase inhibitors.

PMID- 18073531
TI  - Apaf-1 Deficiency Causes Chromosomal Instability.
AB  - Apaf-1 is an essential component of the apoptosome, the molecular complex
      assembled in response to mitochondrial cytochrome c release that promotes caspase
      activation. Apaf-1 expression is suppressed in some malignant tumors, in
      particular melanoma as well as cervical and colorectal carcinoma, in which the
      loss of Apaf-1 expression marks tumor progression and poor prognosis. Recent
      results from our laboratory demonstrate that Apaf-1 has an apoptosis-unrelated
      function that may well account for its role as a tumor suppressor. The knockout
      of apaf-1 (in mice), the knockdown of Apaf-1 (in human cells) and loss of
      function mutations of ced-4 (the Caenorhabditis elegans ortholog of Apaf-1)
      compromise the arrest of DNA synthesis in response to DNA damage, in a context in
      which apoptosis does not occur. Here, we show that the depletion of Apaf-1 also
      sensitizes cells to chromosomal instability induced by different types of DNA
      damage such as cisplatin, UVC light and gamma-irradiation. These results unravel
      a hitherto unsuspected role for Apaf-1 in the maintenance of genomic stability,
      independently from its function in the cell death machinery.

PMID- 18073532
TI  - The E3 ubiquitin ligase EDD regulates S-phase and G(2)/M DNA damage checkpoints.
AB  - The cellular response to DNA damage is critical for maintenance of genomic
      integrity and inhibition of tumorigenesis. Mutations or aberrant expression of
      the E3 ubiquitin ligase EDD have been observed in a number of carcinomas and we
      recently reported that EDD modulates activity of the DNA damage checkpoint
      kinase, CHK2. Here, we demonstrate that EDD is necessary for G(1)/S and intra S
      phase DNA damage checkpoint activation and for the maintenance of G(2)/M arrest
      after double strand DNA breaks. Defective checkpoint activation in EDD-depleted
      cells led to radio-resistant DNA synthesis, premature entry into mitosis,
      accumulation of polyploid cells, and cell death via mitotic catastrophe. In
      addition to decreased CHK2 activation in EDD-depleted cells, the expression of
      several key cell cycle mediators including Cdc25A/C and E2F1 was altered,
      suggesting that these checkpoint defects may be both CHK2-dependent and 
      independent. These data support a role for EDD in the maintenance of genomic
      stability, emphasising the potential importance of dysregulated EDD expression
      and/or function in the evolution of cancer.

PMID- 18073533
TI  - Bilirubin inhibits tumor cell growth via activation of ERK.
AB  - Bilirubin for decades was considered a potentially toxic waste product of heme
      degradation until the discovery that it is a potent antioxidant. Accumulating
      data from observations in humans and experimental studies indicate that the bile
      pigment may be protective against certain diseases. Based on our own observations
      that bilirubin induces cell cycle arrest in abnormally proliferating vascular
      smooth muscle cells and clinical observations describing a lesser incidence of
      cancer in healthy individuals with high normal or slightly elevated serum
      bilirubin levels, we hypothesized that bilirubin might suppress tumor cell
      proliferation in vitro and in vivo. As possible effectors we analyzed key
      proteins that are involved in cell cycle progression and apoptosis. In vivo,
      tumor growth was assessed in BALB/c nude mice bearing HRT-18 colon cancer
      xenografts that were treated with bilirubin. In vitro, we investigated the effect
      of bilirubin on various cell lines and the signaling pathways involved in
      bilirubin action on tumor cell proliferation in HRT-18 cells using western blots.
      Bilirubin potently inhibited tumor cell proliferation in vivo and acted
      cytostatic and pro-apoptotic in vitro. The signaling cascades responsible for
      this action involved induction of p53, p27, hypophosphorylation of the
      retinoblastoma tumor suppressor protein as well as caspase activation. These
      effects were dependent on ERK 1/2. Our study demonstrates that bilirubin may play
      a role in the defense against cancer by interfering with pro-cancerogenic
      signaling pathways.

PMID- 18073534
TI  - Regulation of mitochondrial morphological dynamics during apoptosis by Bcl-2
      family proteins: a key in Bak?
AB  - Early during apoptosis, the mitochondrial network collapses into short punctuate
      fragments. The seemingly morphological change, called mitochondrial
      fragmentation, contributes to mitochondrial injury. Mitochondrial morphology is
      dictated by two opposing processes, fission and fusion. It is unclear how the
      fission-fusion balance is tilted during apoptosis, resulting in mitochondrial
      fragmentation. Emerging evidence has now suggested a regulation of mitochondrial
      morphological dynamics by Bcl-2 family proteins. In this regulation, Bak appears
      to be a key. Through interaction with mitofusins, Bak may block mitochondrial
      fusion to induce fragmentation. By this function, Bak may collaborate with Bax to
      permeabilize mitochondrial outer membrane, leading to the release of apoptogenic
      factors.

PMID- 18073535
TI  - Nitric oxide coordinates cell proliferation and cell movements during early
      development of Xenopus.
AB  - The establishment of a vertebrate body plan during embryogenesis is achieved
      through precise coordination of cell proliferation and morphogenetic cell
      movements. Here we show that nitric oxide (NO) suppresses cell division and
      facilitates cell movements during early development of Xenopus, such that
      inhibition of NO synthase (NOS) increases proliferation in the neuroectoderm and
      suppresses convergent extension in the axial mesoderm and neuroectoderm. NO
      controls cell division and cell movement through two separate signaling pathways.
      Both rely on RhoA-ROCK signaling but can be distinguished by the involvement of
      either guanylate cyclase or the planar cell polarity regulator Dishevelled.
      Through the cGMP-dependent pathway, NO suppresses cell division by negatively
      regulating RhoA and controlling the nuclear distribution of ROCK and p21WAF1.
      Through the cGMP-independent pathway, NO facilitates cell movement by regulating
      the intracellular distribution and level of Dishevelled and the activity of RhoA,
      thereby controlling the activity of ROCK and regulating actin cytoskeleton
      remodeling and cell polarization. Concurrent control by NO helps ensure that the
      crucial processes of cell proliferation and morphogenetic movements are
      coordinated during early development.

PMID- 18073536
TI  - CDC25A levels determine the balance of proliferation and checkpoint response.
AB  - Current evidence suggests that CDC25A is not only a major regulator of both
      G(1)/S and G(2)/M transition during unperturbed cell cycle progression, but also
      a critical checkpoint mediator. While CDC25A is overexpressed in a variety of
      human cancers, a key question remained unanswered whether such overexpression of
      this CDK-activating phosphatase was a mechanism or consequence of accelerated
      proliferation and other malignant phenotypes. Recent studies on the tumor
      suppressive roles of checkpoint proteins suggest that overriding checkpoint
      response leads normal or pre-cancerous cells to genomic instability and
      cumulative malignant changes. Here we provide our views on the role of CDC25A in
      cancer development and genomic stability, discussing insights from our recent
      studies on Cdc25A knockout mice and MMTV-CDC25A transgenic mice.

PMID- 18073537
TI  - Chemosensitizing anti-cancer activity of LFM-A13, a leflunomide metabolite analog
      targeting polo-like kinases.
AB  - LFM-A13 (alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)propenamide)
      has recently been identified as an inhibitor of Polo-like kinases (Plk). LFM-A13
      does not inhibit other serine/threonine kinases including CDK, CHK, RAF, DAPK,
      IKK, IRAK, JNK, MAPK, PKC and SAPK. LFM-A13-treated human cancer cells develop
      abnormal mitotic spindles and G(2)/M-arrest during cell cycle progression. LFM
      A13 was not toxic to rodents or dogs at daily dose levels as high as 100 mg/kg.
      Notably, at a low dose level of 10 mg/kg, which does not result in delayed tumor
      progression in the MMTV/neu transgenic mouse model of HER2 positive breast
      cancer, LFM-A13 markedly enhanced the anti-cancer activity of the mitotic spindle
      poison paclitaxel. These results indicate that LFM-A13 may be useful in the
      treatment of cancer patients.

PMID- 18073538
TI  - CDK2 is dispensable for adult hippocampal neurogenesis.
AB  - Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous
      renewal throughout life. Among cell cycle regulators, cyclin-dependent kinase 2
      (Cdk2) is considered as a major regulator of S-phase entry. We used Cdk2
      deficient mice to decipher the requirement of Cdk2 for the generation of new
      neurons in the adult hippocampus. The quantification of cell cycle markers first
      revealed that the lack of Cdk2 activity does not influence spontaneous or seizure
      induced proliferation of neural progenitor cells (NPC) in the adult DG. Using
      bromodeoxyuridine incorporation assays, we showed that the number of mature
      newborn granule neurons generated de novo was similar in both wild-type (WT) and
      Cdk2-deficient adult mice. Moreover, the apparent lack of cell output reduction
      in Cdk2(-/-) mice DG did not result from a reduction in apoptosis of newborn
      granule cells as analyzed by TUNEL assays. Our results therefore suggest that
      Cdk2 is dispensable for NPC proliferation, differentiation and survival of adult
      born DG granule neurons in vivo. These data emphasize that functional
      redundancies between Cdks also occur in the adult brain at the level of neural
      progenitor cell cycle regulation during hippocampal neurogenesis.

PMID- 18073540
TI  - Hypertonic saline for craniotomy?

PMID- 18073541
TI  - Experience not equal expertise: can simulation be used to tell the difference?

PMID- 18073542
TI  - Noble meets nouveau: a shared anesthetic binding site for xenon and isoflurane on
      a glutamate receptor.

PMID- 18073543
TI  - Effect of equiosmolar solutions of mannitol versus hypertonic saline on
      intraoperative brain relaxation and electrolyte balance.
AB  - BACKGROUND: The purpose of the study was to compare the effect of equiosmolar
      solutions of mannitol and hypertonic saline (HS) on brain relaxation and
      electrolyte balance. METHODS: After institutional review board approval and
      informed consent, patients with American Society of Anesthesiologists physical
      status II-IV, scheduled to undergo craniotomy for various brain pathologies, were
      enrolled into this prospective, randomized, double-blind study. Patients received
      5 ml/kg 20% mannitol (n = 20) or 3% HS (n = 20). Partial pressure of carbon
      dioxide in arterial blood was maintained at 35-40 mmHg, and central venous
      pressure was maintained at 5 mmHg or greater. Hemodynamic variables, fluid
      balance, blood gases, electrolytes, lactate, and osmolality (blood, cerebrospinal
      fluid, urine) were measured at 0, 15, 30, and 60 min and 6 h after infusion;
      arteriovenous difference of oxygen, glucose, and lactate were calculated. The
      surgeon assessed brain relaxation on a four-point scale (1 = relaxed, 2 =
      satisfactory, 3 = firm, 4 = bulging). Appropriate statistical tests were used for
      comparison; P < 0.05 was considered significant. RESULTS: There was no difference
      in brain relaxation (mannitol = 2, HS = 2 points; P = 0.8) or cerebral
      arteriovenous oxygen and lactate difference between HS and mannitol groups. Urine
      output with mannitol was higher than with HS (P < 0.03) and was associated with
      higher blood lactate over time (P < 0.001, compared with HS). Cerebrospinal fluid
      osmolality increased at 6 h in both groups (P < 0.05, compared with baseline). HS
      caused an increase in sodium in cerebrospinal fluid over time (P < 0.001,
      compared with mannitol). CONCLUSION: Mannitol and HS cause an increase in
      cerebrospinal fluid osmolality, and are associated with similar brain relaxation
      scores and arteriovenous oxygen and lactate difference during craniotomy.

PMID- 18073544
TI  - Performance of residents and anesthesiologists in a simulation-based skill
      assessment.
AB  - BACKGROUND: Anesthesiologists and anesthesia residents are expected to acquire
      and maintain skills to manage a wide range of acute intraoperative anesthetic
      events. The purpose of this study was to determine whether an inventory of
      simulated intraoperative scenarios provided a reliable and valid measure of
      anesthesia residents' and anesthesiologists' skill. METHODS: Twelve simulated
      acute intraoperative scenarios were designed to assess the performance of 64
      residents and 35 anesthesiologists. The participants were divided into four
      groups based on their training and experience. There were 31 new CA-1, 12
      advanced CA-1, and 22 CA-2/CA-3 residents as well as a group of 35 experienced
      anesthesiologists who participated in the assessment. Each participant managed a
      set of simulated events. The advanced CA-1 residents, CA-2/CA-3 residents, and 35
      anesthesiologists managed 8 of 12 intraoperative simulation exercises. The 31 CA
      1 residents each managed 3 intraoperative scenarios. RESULTS: The new CA-1
      residents received lower scores on the simulated intraoperative events than the
      other groups of participants. The advanced CA-1 residents, CA-2/CA-3 residents,
      and anesthesiologists performed similarly on the overall assessment. There was a
      wide range of scores obtained by individuals in each group. A number of the
      exercises were difficult for the majority of participants to recognize and treat,
      but most events effectively discriminated among participants who achieved higher
      and lower overall scores. CONCLUSION: This simulation-based assessment provided a
      valid method to distinguish the skills of more experienced anesthesia residents
      and anesthesiologists from residents in early training. The overall score
      provided a reliable measure of a participant's ability to recognize and manage
      simulated acute intraoperative events. Additional studies are needed to determine
      whether these simulation-based assessments are valid measures of clinical
      performance.

PMID- 18073545
TI  - Laryngeal mask airway is associated with an increased incidence of adverse
      respiratory events in children with recent upper respiratory tract infections.
AB  - BACKGROUND: The laryngeal mask airway (LMA) has been advocated as an alternative
      technique to tracheal intubation for airway management of children with recent
      upper respiratory tract infections (URIs). The authors determined the occurrence
      of adverse respiratory events and identified the associated risk factors to
      assess the safety of LMA in children. METHODS: During a period of 5 months,
      parents of children scheduled to undergo general anesthesia with an LMA were
      asked to fill out a questionnaire regarding their child's medical history and
      potential symptoms of URI. In addition, all episodes of adverse respiratory
      events in the perioperative period (laryngospasm, bronchospasm, coughing, airway
      obstruction, and oxygen desaturation) as well as details of anesthesia management
      were recorded. RESULTS: Among the 831 children included in the study, 27%
      presented with a history of a recent URI within the last 2 weeks before
      anesthesia. The presence of a recent URI doubled the incidence of laryngospasm
      (odds ratio, 2.6; 95% confidence interval, 1.3-5.0), coughing (odds ratio, 2.7;
      95% confidence interval, 1.7-4.3), and oxygen desaturation (odds ratio, 1.9; 95%
      confidence interval, 1.2-2.8). This incidence was even higher in young children;
      in those undergoing ear, nose, and throat surgery; and when there were multiple
      attempts to insert the LMA. CONCLUSION: An LMA used in children with recent URIs
      was associated with a higher incidence of laryngospasm, cough, and oxygen
      desaturation compared with healthy children. However, the overall incidence of
      adverse respiratory events was low, suggesting that if anesthesiologists allow at
      least a 2-week interval after a URI, they can safely proceed with anesthesia
      using an LMA.

PMID- 18073546
TI  - A randomized trial of ultrasound image-based skin surface marking versus real
      time ultrasound-guided internal jugular vein catheterization in infants.
AB  - BACKGROUND: Ultrasound-guided central venous catheterization has been recommended
      to increase the procedural success rate and enhance patient safety. However, few
      studies have examined the potential advantages of one ultrasound technique with
      another, specifically in small infants. METHODS: The authors randomly assigned 60
      neonates and infants weighing less than 7.5 kg to an ultrasound-guided skin
      marking method (n = 27) versus real-time ultrasound-assisted internal jugular
      venous catheterization (n = 33). The times to successful puncture of the internal
      jugular vein and to catheterization were measured. Attempts at needle punctures
      for successful catheterization were counted. Procedural complications were
      recorded. RESULTS: In the real-time group, compared with the skin- marking group,
      venous puncture was completed faster (P = 0.03), the time required to catheterize
      was shorter (P < 0.01), and fewer needle passes were needed. Specifically, fewer
      than three attempts at puncture were made in 100% of patients in the real-time
      group, versus 74% of patients in the skin-marking group (P < 0.01). A hematoma
      and an arterial puncture occurred in one patient each in the skin-marking group.
      CONCLUSIONS: The real-time ultrasound guidance method could enhance procedural
      efficacy and safety of internal jugular catheterization in neonates and infants.

PMID- 18073547
TI  - Effects of the beach chair position, positive end-expiratory pressure, and
      pneumoperitoneum on respiratory function in morbidly obese patients during
      anesthesia and paralysis.
AB  - BACKGROUND: The authors studied the effects of the beach chair (BC) position, 10
      cm H2O positive end-expiratory pressure (PEEP), and pneumoperitoneum on
      respiratory function in morbidly obese patients undergoing laparoscopic gastric
      banding. METHODS: The authors studied 20 patients (body mass index 42 +/- 5
      kg/m2) during the supine and BC positions, before and after pneumoperitoneum was
      instituted (13.6 +/- 1.2 mmHg). PEEP was applied during each combination of
      position and pneumoperitoneum. The authors measured elastance (E,rs) of the
      respiratory system, end-expiratory lung volume (helium technique), and arterial
      oxygen tension. Pressure-volume curves were also taken (occlusion technique).
      Patients were paralyzed during total intravenous anesthesia. Tidal volume (10.5
      +/- 1 ml/kg ideal body weight) and respiratory rate (11 +/- 1 breaths/min) were
      kept constant throughout. RESULTS: In the supine position, respiratory function
      was abnormal: E,rs was 21.71 +/- 5.26 cm H2O/l, and end-expiratory lung volume
      was 0.46 +/- 0.1 l. Both the BC position and PEEP improved E,rs (P < 0.01). End
      expiratory lung volume almost doubled (0.83 +/- 0.3 and 0.85 +/- 0.3 l, BC and
      PEEP, respectively; P < 0.01 vs. supine zero end-expiratory pressure), with no
      evidence of lung recruitment (0.04 +/- 0.1 l in the supine and 0.07 +/- 0.2 in
      the BC position). PEEP was associated with higher airway pressures than the BC
      position (22.1 +/- 2.01 vs. 13.8 +/- 1.8 cm H2O; P < 0.01). Pneumoperitoneum
      further worsened E,rs (31.59 +/- 6.73; P < 0.01) and end-expiratory lung volume
      (0.35 +/- 0.1 l; P < 0.01). Changes of lung volume correlated with changes of
      oxygenation (linear regression, R2 = 0.524, P < 0.001) so that during
      pneumoperitoneum, only the combination of the BC position and PEEP improved
      oxygenation. CONCLUSIONS: The BC position and PEEP counteracted the major
      derangements of respiratory function produced by anesthesia and paralysis. During
      pneumoperitoneum, only the combination of the two maneuvers improved oxygenation.

PMID- 18073548
TI  - A single dose of propofol at the end of surgery for the prevention of emergence
      agitation in children undergoing strabismus surgery during sevoflurane
      anesthesia.
AB  - BACKGROUND: Emergence agitation in children after sevoflurane is common.
      Different drugs have been used to decrease its occurrence with variable efficacy.
      The authors compared the incidence and severity of emergence agitation in
      children who received a single dose of propofol at the end of strabismus surgery
      versus children who received saline. METHODS: In this prospective, randomized,
      double-blind study, the authors enrolled 80 healthy children aged 2-6 yr. The
      children were randomly allocated to the propofol group (n = 41), which received 1
      mg/kg propofol at the end of surgery, or to the saline group (n = 39), which
      received saline. RESULTS: The mean scores on the Pediatric Anesthesia Emergence
      Delirium scale were significantly lower in the propofol group compared with the
      saline group (8.6 +/- 3.9 vs. 11.5 +/- 4.5; P = 0.004). Also, the incidence of
      agitation was significantly lower in the propofol group compared with the saline
      group (19.5% vs. 47.2%; P = 0.01). A threshold score greater than 10 on the
      Pediatric Anesthesia Emergence Delirium scale was the best discriminator between
      presence and absence of emergence agitation. Times to removal of the laryngeal
      mask airway (10.6 +/- 1.5 vs. 9.4 +/- 1.9 min; P = 0.004) and emergence times
      (23.4 +/- 5.7 vs. 19.7 +/- 5 min; P = 0.004) were significantly longer in the
      propofol group. However, discharge times were similar between the two groups
      (propofol: 34.1 +/- 8.4 min; saline: 34.9 +/- 8.6 min). More parents in the
      propofol group were satisfied. CONCLUSIONS: In children undergoing strabismus
      surgery, 1 mg/kg propofol at the end of surgery after discontinuation of
      sevoflurane decreases the incidence of agitation and improves parents'
      satisfaction without delaying discharge from the postanesthesia care unit.

PMID- 18073549
TI  - Deterioration of regional wall motion immediately after coronary artery bypass
      graft surgery is associated with long-term major adverse cardiac events.
AB  - BACKGROUND: Patients undergoing coronary artery bypass graft (CABG) surgery
      frequently develop wall motion abnormalities diagnosed by intraoperative
      transesophageal echocardiography. However, the relation between deterioration in
      wall motion and postoperative morbidity or mortality is unclear. Therefore, the
      authors hypothesized that deterioration in intraoperative left ventricular
      regional wall motion immediately after CABG surgery is associated with a higher
      risk of adverse cardiac events. METHODS: With institutional review board
      approval, data were gathered from 1,412 CABG surgery patients. Echocardiographic
      wall motion score (WMS) was derived using a 16-segment model. Outcomes data were
      gathered for up to 2 yr after surgery. The primary outcome, major adverse cardiac
      event, was a composite index of myocardial infarction, need for subsequent
      coronary revascularization, or all-cause mortality during the follow-up period.
      RESULTS: Two hundred twenty-one patients (16%) had 254 primary outcome events
      during follow-up. Postbypass WMS did not change in 812 patients (58%),
      deteriorated in 219 patients (16%), and improved in 368 patients (26%). Kaplan
      Meier analysis showed that patients with deterioration in WMS after CABG
      experienced significantly lower major adverse cardiac event-free survival than
      patients with either no change or improvement in WMS (P = 0.004). Cox
      proportional hazards regression modeling revealed a significant association
      between deterioration in WMS and the composite adverse outcome (hazard ratio,
      1.47 [1.06-2.03]; P = 0.02). CONCLUSIONS: The authors confirmed their hypothesis
      that deterioration in wall motion detected by intraoperative echocardiography
      after CABG surgery is associated with increased risk of long-term adverse cardiac
      morbidity. Worsening wall motion after CABG surgery should be considered a
      prognostic indicator of adverse cardiovascular outcome.

PMID- 18073550
TI  - Cerebral cortex activation during experimentally induced ventilator fighting in
      normal humans receiving noninvasive mechanical ventilation.
AB  - BACKGROUND: Mechanical ventilation is delivered to sedated patients during
      anesthesia, but also to nonsedated patients (ventilator weaning, noninvasive
      ventilation). In these circumstances, patient-ventilator asynchrony may occur,
      provoking discomfort and unduly increasing work of breathing. In certain cases,
      it is associated with an increased inspiratory load. Inspiratory loading in awake
      humans activates the premotor cortical regions, as illustrated by the occurrence
      of electroencephalographic premotor potentials. In normal humans during
      noninvasive ventilation, the authors used an experimental model of patient
      ventilator asynchrony to determine whether premotor cortical activation occurs in
      this setting. METHODS: Noninvasive pressure support ventilation was administered
      to seven healthy volunteers aged 22-27 yr with continuous electroencephalographic
      recordings in Cz. The ventilator settings were first adjusted to make the
      subjects feel comfortable ("comfort"), and then modified to induce respiratory
      "discomfort" (evaluated on a 10-cm visual analog scale). This was achieved by
      setting the ventilator to a higher trigger level, reducing the slope of the
      pressure support rise, and reducing the level of pressure support. The settings
      were finally brought back to their initial values. To identify a respiratory
      related premotor activity, a minimum of 80 preinspiratory electroencephalographic
      epochs were averaged. RESULTS: Altering ventilator settings induced respiratory
      discomfort (average visual scale 4 [1.5-6.0] vs. 0 [0-1.0] cm during "comfort"; P
      < 0.0001). This was associated with premotor potentials in all cases, which
      disappeared upon return to "comfort." CONCLUSIONS: This study indicates that
      "ventilator fighting" in healthy humans is associated with an activation of
      higher cerebral areas. Premotor potentials could thus be markers of patient
      ventilator asynchrony at the brain level. Both corroboration in patients and the
      elucidation of the causative or reactive nature of the association are needed
      before determining clinical implications.

PMID- 18073551
TI  - Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor
      by the anesthetics xenon and isoflurane: evidence from molecular modeling and
      electrophysiology.
AB  - BACKGROUND: Inhibition of N-methyl-D-aspartate (NMDA) receptors by anesthetic
      gases and vapors may play an important role in anesthesia and neuroprotection.
      However, the site of action of these agents on the NMDA receptor is unknown. The
      authors show that xenon and isoflurane compete for the binding of the coagonist
      glycine on the NMDA receptor NR1 subunit. METHODS: Using a novel application of
      grand canonical Monte Carlo simulations, the authors predict the binding site of
      xenon on NMDA receptors. They test this prediction using electrophysiology on
      recombinant NMDA receptors. RESULTS: The authors' modeling predicts that xenon
      binds at the glycine site of the NMDA receptor. The authors show that inhibition
      of NMDA receptors by xenon and isoflurane increases as glycine concentration is
      decreased, consistent with the prediction of competitive inhibition at the
      glycine site. Lineweaver-Burk analysis shows that isoflurane inhibition seems
      purely competitive with glycine, but for xenon, there is an additional component
      of noncompetitive inhibition. The loss of inhibitory effect of xenon and
      isoflurane in mutant NR1(F639A)/NR2A receptors is explained by increased glycine
      affinity of the mutant receptors, and inhibition is restored at low glycine
      concentrations. CONCLUSIONS: Xenon and isoflurane inhibit NMDA receptors by
      binding at the same site as the coagonist glycine. This finding may have
      important implications for general anesthesia and neuroprotection.
      Neuroprotectants that act at the glycine site of the NMDA receptor antagonists
      are well tolerated in patients, being devoid of psychotomimetic side effects, and
      the mechanism of inhibition may play a role in their clinical profile.

PMID- 18073552
TI  - Cerebral air emboli differentially alter outcome after cardiopulmonary bypass in
      rats compared with normal circulation.
AB  - BACKGROUND: Cerebral air emboli (CAE) are thought to contribute to adverse
      cerebral outcomes following cardiac surgery with cardiopulmonary bypass (CPB).
      This study was designed to investigate the effect of escalating volumes of CAE on
      survival and neurologic and histologic outcomes. In addition, the effect of xenon
      administration during CAE on these outcomes was determined. METHODS: With
      institutional review board approval, four groups were studied (n = 15). In two
      CPB-CAE groups, rats were subjected to 90 min CPB with 10 repetitively
      administered CAE. Rats in two sham-CAE groups were also exposed to CAE but not to
      CPB. Rats were randomly assigned to sequential dose cohorts receiving CAE ranging
      from 0.2 to 10 microl in a dose-escalating fashion. Groups were further
      subdivided into xenon (56%) and nitrogen groups. Rats with severe neurologic
      damage were killed; others were neurologically tested until postoperative day 7,
      when infarct volumes were determined. Survival and neurologic and histologic
      outcomes were tested with logistic regression analyses (P < 0.05). RESULTS: This
      study demonstrates a dose-dependent relation between CAE volumes and survival,
      neurologic outcome, and histologic outcome. For all outcomes, CPB adversely
      affected the dose-effect curves compared with sham-CAE groups (P < 0.05). Xenon
      demonstrated no impact on either outcome. CONCLUSIONS: This study describes the
      successful incorporation of CAE in a rodent CPB model and allows identifying
      suitable CAE volumes for subsequent studies. CAE exhibit a differential effect on
      outcome in rats undergoing CPB versus those not exposed to CPB. Perioperative
      administration of xenon remained without any effect on outcome.

PMID- 18073553
TI  - Hydrocortisone preserves the vascular barrier by protecting the endothelial
      glycocalyx.
AB  - BACKGROUND: Hydrocortisone protects against ischemia-reperfusion injury, reduces
      paracellular permeability for macromolecules, and is routinely applied in the
      prevention of interstitial edema. Healthy vascular endothelium is coated by the
      endothelial glycocalyx, diminution of which increases capillary permeability,
      suggesting that the glycocalyx is a target for hydrocortisone action. METHODS:
      Isolated guinea pig hearts were perfused with Krebs-Henseleit buffer.
      Hydrocortisone was applied in a stress dose (10 microg/ml) before inducing 20 min
      of ischemia (37 degrees C). Hearts were reperfused for 20 min at constant flow
      (baseline perfusion pressure, 70 cm H2O) with Krebs-Henseleit buffer or Krebs
      Henseleit buffer plus 2 g% hydroxyethyl starch (130 kd). Coronary net fluid
      filtration was assessed directly by measuring transudate formation on the
      epicardial surface. Hearts were perfusion fixed to visualize the glycocalyx.
      RESULTS: Ischemia-induced degradation of the glycocalyx enhanced coronary
      perfusion pressure (118.8 +/- 17.3 cm H2O) and increased vascular permeability (8
      +/- 0.2 microl x min(-1) x cm H2O(-1) at baseline vs. 34 +/- 3.3 microl x min(-1)
      x cm H2O(-1) after reperfusion). Enzymatic digestion of the glycocalyx
      (heparinase) elicited similar effects. Hydrocortisone reduced postischemic
      oxidative stress, perfusion pressure (86.3 +/- 6.4 cm H2O), and transudate
      formation (11 +/- 0.6 microl x min(-1) x cm H2O(-1)). Applying colloid augmented
      this (70.6 +/- 5.6 cm H2O and 9 +/- 0.5 microl x min(-1) x cm H2O(-1)).
      Postischemic shedding of syndecan-1, heparan sulfate, and hyaluronan was
      inhibited by hydrocortisone, as was release of histamine from resident mast
      cells. Electron microscopy revealed a mostly intact glycocalyx after
      hydrocortisone treatment, but not after heparinase treatment. CONCLUSIONS:
      Hydrocortisone preserves the endothelial glycocalyx, sustaining the vascular
      barrier and reducing interstitial edema. The effect of colloids suggests that
      prevention of postischemic rise in coronary resistance by hydrocortisone could
      also be based on alleviation of endothelial swelling. Stabilization of myocardial
      mast cells by hydrocortisone may account for the mitigated inflammatory affect of
      ischemia-reperfusion.

PMID- 18073554
TI  - Dose-dependent effects of smoked cannabis on capsaicin-induced pain and
      hyperalgesia in healthy volunteers.
AB  - BACKGROUND: Although the preclinical literature suggests that cannabinoids
      produce antinociception and antihyperalgesic effects, efficacy in the human pain
      state remains unclear. Using a human experimental pain model, the authors
      hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced
      by intradermal capsaicin. METHODS: In a randomized, double-blinded, placebo
      controlled, crossover trial in 15 healthy volunteers, the authors evaluated
      concentration-response effects of low-, medium-, and high-dose smoked cannabis
      (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannabinol by weight) on pain and
      cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected
      into opposite forearms 5 and 45 min after drug exposure, and pain, hyperalgesia,
      tetrahydrocannabinol plasma levels, and side effects were assessed. RESULTS: Five
      minutes after cannabis exposure, there was no effect on capsaicin-induced pain at
      any dose. By 45 min after cannabis exposure, however, there was a significant
      decrease in capsaicin-induced pain with the medium dose and a significant
      increase in capsaicin-induced pain with the high dose. There was no effect seen
      with the low dose, nor was there an effect on the area of hyperalgesia at any
      dose. Significant negative correlations between pain perception and plasma delta
      9-tetrahydrocannabinol levels were found after adjusting for the overall dose
      effects. There was no significant difference in performance on the
      neuropsychological tests. CONCLUSIONS: This study suggests that there is a window
      of modest analgesia for smoked cannabis, with lower doses decreasing pain and
      higher doses increasing pain.

PMID- 18073555
TI  - Adenosine A1 but not A2a receptor agonist reduces hyperalgesia caused by a
      surgical incision in rats: a pertussis toxin-sensitive G protein-dependent
      process.
AB  - BACKGROUND: Activation of A1 adenosine receptors (A1Rs) causes antinociception
      after nerve injury and inflammation. However, the role of A2a adenosine receptors
      (A2aRs) for pain processing is less clear. In the current study, the authors
      investigated the role of spinal adenosine A1Rs and A2aRs for the maintenance of
      mechanical hyperalgesia in an animal model for postoperative pain. METHODS: Rats
      with intrathecal catheters were anesthetized and underwent plantar incision.
      Spontaneous pain behavior and withdrawal threshold to punctuate stimulation were
      measured before and after administration of intrathecal R-phenylisopropyl
      adenosine (R-PIA; A1R agonist), 2-w p-2-carbonyl-ethyl-phenylethylaminox-5X-N
      ethylcarboxami-doadenosine (CGS21680; A2aR agonist), or vehicle. In separate
      groups of animals, the effects of pertussis toxin, forskolin, glibenclamide, 4
      aminopyridine, tetraethylammonium, apamin, charybdotoxin, or margatoxin on R-PIA
      induced antinociception were examined. RESULTS: Intrathecal administration of 5
      nmol R-PIA but not 10 nmol CGS21680 decreased nonevoked spontaneous pain
      behavior. Furthermore, intrathecal administration of R-PIA but not of CGS21680
      increased withdrawal thresholds after incision. Pretreatment with pertussis toxin
      and administration of forskolin, glibenclamide, 4-aminopyridine, and
      tetraethylammonium inhibited R-PIA-induced antinociception. In addition,
      intrathecal administration of apamin, charybdotoxin, or margatoxin did not modify
      mechanical hypoalgesia mediated by R-PIA. CONCLUSIONS: Spinal A1Rs but not A2aRs
      play an important role in the maintenance of nonevoked and evoked pain behaviors
      after an incision. Furthermore, A1R-induced spinal antinociception is mediated by
      interactions with pertussis toxin-sensitive G proteins. In addition, the opening
      of adenosine triphosphate-sensitive K channels but not of calcium-activated
      potassium channels and voltage-gated Kv1.3 or Kv1.6 channels contribute to the
      antinociceptive effect of A1R agonists.

PMID- 18073556
TI  - Differential presynaptic effects of opioid agonists on Adelta- and C-afferent
      glutamatergic transmission to the spinal dorsal horn.
AB  - BACKGROUND: Although intrathecal administration of opioids produces
      antinociceptive effects in the spinal cord, it has not been established whether
      intrathecal opioid application more effectively terminates C fiber-mediated pain
      than A fiber-mediated pain. Here, the authors focus on the differences in opioid
      actions on Adelta- and C-afferent responses. METHODS: Using the whole cell patch
      clamp technique, the authors investigated the presynaptic inhibitory actions of
      micro-, delta-, and kappa-opioid receptor agonists on primary afferent-evoked
      excitatory postsynaptic currents (EPSCs) in substantia gelatinosa neurons of
      adult rat spinal cord slices. RESULTS: The micro agonist DAMGO (0.1, 1 microM)
      reduced the amplitude of glutamatergic monosynaptic Adelta- or C fiber-evoked
      EPSCs. C fiber-evoked EPSCs were inhibited to a greater extent than Adelta fiber
      evoked EPSCs. The delta agonist DPDPE (1, 10 microM) produced modest inhibition
      of Adelta- or C fiber-evoked EPSCs. In contrast, the kappa agonist U69593 (1
      microM) did not affect the amplitude of either Adelta or C fiber-evoked EPSCs.
      CONCLUSIONS: These results indicate that opioids suppress excitatory synaptic
      transmission mainly through activation of micro receptors on primary afferent C
      fibers. Given that the substantia gelatinosa is the main termination of Adelta
      and C fibers transmitting nociceptive information, the current findings may
      partially explain the different potency of opioid agonists.

PMID- 18073557
TI  - Persistent low-frequency spontaneous discharge in A-fiber and C-fiber primary
      afferent neurons during an inflammatory pain condition.
AB  - BACKGROUND: Primary afferent nociceptor sensitization and its accompanying
      spontaneous discharge are believed to be the proximate cause of the spontaneous
      pain and hypersensitivity that follow an acute tissue injury. Evidence for this
      comes almost entirely from studies limited to the first few minutes to an hour or
      two after injury, when the inflammatory reaction to injury has just begun.
      However, there is evidence that inflammatory pain mechanisms differ from acute
      pain mechanisms and that the mechanisms that drive and modulate inflammatory pain
      may evolve over time. METHODS: The authors surveyed spontaneous afferent
      discharge in rats with hind paw inflammation evoked by complete Freund adjuvant
      over the entire 14 days of the inflammatory pain condition, as determined in
      parallel experiments assessing allodynia and hyperalgesia. RESULTS: Inflammation
      evoked heat hyperalgesia, mechanoallodynia, and mechanohyperalgesia began within
      hours, persisted until at least day 7, and resolved by day 14. A large percentage
      (23%) of A fibers had spontaneous discharge 2 days after inflammation, but the
      incidence was much reduced (to 7-9%) by 7 and 14 days. At all times, the A-fiber
      discharge frequency was low (<3.0 Hz) or very low (<0.3 Hz). A large percentage
      (24%) of C fibers had spontaneous discharge 2 and 7 days after inflammation, but
      this also declined to near control levels by day 14; C-fiber discharge frequency
      was also always low (most at 0.3-1.0 Hz). CONCLUSIONS: The pain, allodynia, and
      hyperalgesia associated with an established inflammatory condition are associated
      with a persistent low-frequency spontaneous discharge in both A-fiber and C-fiber
      sensory afferents.

PMID- 18073558
TI  - Nitric oxide: involvement in the effects of anesthetic agents.
AB  - There has been an explosive increase in the amount of interesting information
      about the physiologic and pathophysiologic roles of nitric oxide in
      cardiovascular, nervous, and immune systems. The possible involvement of the
      nitric oxide-cyclic guanosine monophosphate pathway in the effects of anesthetic
      agents has been the focus of many investigators. Relaxations of cerebral and
      peripheral arterial smooth muscle as well as increases in cerebral and other
      regional blood flows induced by anesthetic agents are mediated mainly via nitric
      oxide released from the endothelium and/or the nitrergic nerve and also via
      prostaglandin I2 or endothelium-derived hyperpolarizing factor. Preconditioning
      with volatile anesthetics protects against ischemia-reperfusion-induced
      myocardial dysfunction and cell death or neurotoxicity, possibly through nitric
      oxide release. Inhibition of nitric oxide synthase decreases the anesthetic
      requirement. Involvement of nitric oxide in the effects of volatile, intravenous,
      and local anesthetics differs. This review article includes a summary of
      information about the sites and mechanisms by which various anesthetic agents
      interact with the nitric oxide-cyclic guanosine monophosphate system.

PMID- 18073559
TI  - Hepatotoxicity after desflurane anesthesia in a 15-month-old child with Mobius
      syndrome after previous exposure to isoflurane.

PMID- 18073560
TI  - Subacute spinal subarachnoid hematoma after spinal anesthesia that causes mild
      neurologic deterioration.

PMID- 18073562
TI  - Cognitive impairment due to surgery or postoperative complications?

PMID- 18073563
TI  - Gas embolisms revisited.

PMID- 18073564
TI  - Prevention of vascular air embolism.

PMID- 18073565
TI  - Externally pressurizing salvaged blood reinfusion bags: predictable, preventable
      cause of fatal air embolism.

PMID- 18073566
TI  - Hair splitting, air embolism, and transesophageal echocardiography.

PMID- 18073568
TI  - Vascular air embolism: lung injury and its pathophysiology also need to be
      considered.

PMID- 18073569
TI  - Sevoflurane and epileptiform extrapolation?

PMID- 18073570
TI  - Nasotracheal intubation in children.

PMID- 18073573
TI  - More about telescoping for nasotracheal intubation in children.

PMID- 18073575
TI  - Electroconvulsive therapy: compassion in care and risk-benefits of discomfort.

PMID- 18073576
TI  - A prospective study of pain at rest: incidence and characteristics of an
      unrecognized symptom in surgical and trauma versus medical intensive care unit
      patients.

PMID- 18073577
TI  - A post hoc analysis of research study staffing: budgetary effects of the Health
      Insurance Portability and Accountability Act on research staff work hours during
      a prospective, randomized clinical trial.

PMID- 18073579
TI  - The continuum of translation research in genomic medicine: how can we accelerate
      the appropriate integration of human genome discoveries into health care and
      disease prevention?
AB  - Advances in genomics have led to mounting expectations in regard to their impact
      on health care and disease prevention. In light of this fact, a comprehensive
      research agenda is needed to move human genome discoveries into health practice
      in a way that maximizes health benefits and minimizes harm to individuals and
      populations. We present a framework for the continuum of multidisciplinary
      translation research that builds on previous characterization efforts in genomics
      and other areas in health care and prevention. The continuum includes four phases
      of translation research that revolve around the development of evidence-based
      guidelines. Phase 1 translation (T1) research seeks to move a basic genome-based
      discovery into a candidate health application (e.g., genetic test/intervention).
      Phase 2 translation (T2) research assesses the value of a genomic application for
      health practice leading to the development of evidence-based guidelines. Phase 3
      translation (T3) research attempts to move evidence-based guidelines into health
      practice, through delivery, dissemination, and diffusion research. Phase 4
      translation (T4) research seeks to evaluate the "real world" health outcomes of a
      genomic application in practice. Because the development of evidence-based
      guidelines is a moving target, the types of translation research can overlap and
      provide feedback loops to allow integration of new knowledge. Although it is
      difficult to quantify how much of genomics research is T1, we estimate that no
      more than 3% of published research focuses on T2 and beyond. Indeed, evidence
      based guidelines and T3 and T4 research currently are rare. With continued
      advances in genomic applications, however, the full continuum of translation
      research needs adequate support to realize the promise of genomics for human
      health.

PMID- 18073580
TI  - Defining purpose: a key step in genetic test evaluation.

PMID- 18073581
TI  - Five common gene variants identify elevated genetic risk for coronary heart
      disease.
AB  - PURPOSE: Because multiple genetic variants influence risk for coronary heart
      disease, we combined multiple variants that had been associated with coronary
      heart disease in several studies into a genetic risk score and asked whether a
      high genetic risk score would be significantly associated with coronary heart
      disease after accounting for traditional risk factors. METHODS: We considered
      five variants that were associated with coronary heart disease in two studies and
      confirmed in the Atherosclerosis Risk in Communities study: rs20455 (KIF6),
      rs3900940 (MYH15), rs7439293 (PALLD), rs2298566 (SNX19), and rs1010 (VAMP8). We
      calculated a genetic risk score for each Atherosclerosis Risk in Communities
      study participant and estimated the hazard ratio for incident coronary heart
      disease of a high genetic risk score (compared with not-high) in Cox models that
      adjusted for traditional risk factors during a median of 13 years of follow-up.
      RESULTS: For white participants with a high genetic risk score (4% of the 9129
      whites), compared with those without a high genetic risk score, the hazard ratio
      for incident coronary heart disease was 1.57 (95% confidence interval 1.21-2.04;
      P = 0.001). Internal validation using bootstrap samples estimated that a hazard
      ratio of 1.43 could be expected in external populations. CONCLUSIONS: After
      adjusting for traditional risk factors, those with a high genetic risk score had
      a 57% increased risk of incident coronary heart disease in the Atherosclerosis
      Risk in Communities study.

PMID- 18073582
TI  - Molecular analysis of the CHD7 gene in CHARGE syndrome: identification of 22
      novel mutations and evidence for a low contribution of large CHD7 deletions.
AB  - PURPOSE: Autosomal dominant CHARGE syndrome (OMIM no. 214800) is characterized by
      choanal atresia or cleft lip or palate, ocular colobomas, cardiovascular
      malformations, retardation of growth, ear anomalies, and deafness, and is caused
      by mutations in the CHD7 gene. Here, we describe the outcome of a molecular
      genetic analysis in 18 Finnish and 56 German patients referred for molecular
      confirmation of the clinical diagnosis of suspected CHARGE syndrome. METHODS:
      Quantitative real-time polymerase chain reaction or multiplex ligation-dependent
      probe amplification assays did not reveal deletions in mutation negative cases,
      suggesting that larger CHD7 deletions are not a major cause of CHARGE syndrome.
      RESULTS: In this group of 74 patients, we found mutations in 30 cases. 22
      mutations were novel, including 11 frameshift, 5 nonsense, 3 splice-site, and 3
      missense mutations. One de novo frameshift mutation was found in the last exon
      and is expected to result in a minimally shortened CHD7 polypeptide. Because the
      mutation is associated with a typical CHARGE syndrome phenotype, it may indicate
      the presence of an as yet unknown functional domain in the very carboxyterminal
      end of CHD7. CONCLUSIONS: Our mutation detection rate of 40.5% is reflective of
      screening an unselected sample population referred for CHD7 testing based on
      suspected clinical diagnosis of CHARGE syndrome and not for having met strict
      clinical criteria for this disorder.

PMID- 18073583
TI  - Pharmacogenomic testing to prevent aminoglycoside-induced hearing loss in cystic
      fibrosis patients: potential impact on clinical, patient, and economic outcomes.
AB  - BACKGROUND: Aminoglycosides are commonly used in cystic fibrosis patients to
      treat Pseudomonas aeruginosa respiratory infections. Aminoglycoside-induced
      hearing loss may occur in 1%-15% of patients with cystic fibrosis, ranging from
      mild to severe. Recently, a genetic test to identify patients with a
      mitochondrial mutation (A1555G) that may predispose patients to this adverse
      event has become available. Although the A1555G variant is very rare, it seems to
      confer a high risk of severe hearing loss in patients exposed to aminoglycosides.
      OBJECTIVE: The objective was to evaluate the potential clinical, patient, and
      economic outcomes associated with the use of A1555G testing in a cystic fibrosis
      population, and explore data gaps and uncertainty in its clinical implementation.
      METHODS: We developed a decision-analytic model to evaluate a hypothetical cohort
      of patients with cystic fibrosis from a societal perspective. Clinical and
      economic data were derived primarily from a critical literature review. The
      incidence of aminoglycoside-induced severe hearing loss, quality-adjusted life
      years, and total health care costs were evaluated. Sensitivity analyses were
      conducted to evaluate uncertainty in our results. RESULTS: In the base-case
      analysis, A1555G testing decreased the risk of severe aminoglycoside-induced
      hearing loss by 0.12% in the cystic fibrosis population. The discounted
      incremental cost per quality-adjusted life-years gained was $79,300, but varied
      widely from $33,000 to testing being dominated by the no testing strategy (higher
      costs and lower quality-adjusted life-years with testing) in sensitivity
      analyses. If avoidance of aminoglycosides in patients testing positive leads to
      an absolute increase in the lifetime risk of death from Pseudomonas infection of
      0.8% or greater, A1555G testing would lead to a decrease in quality-adjusted life
      years. CONCLUSIONS: The results of our analysis suggest that there are
      significant data gaps and uncertainty in the outcomes with A1555G testing, but it
      is not likely cost-effective, and could lead to worse patient outcomes due to
      avoidance of first-line therapy in the >95% of patients who are false-positives.
      Additional research is needed before pharmacogenetic testing for the A1555G
      mitochondrial mutation can be recommended, even in a population with a high
      likelihood of exposure to aminoglycosides.

PMID- 18073584
TI  - Health-related quality of life in a racially diverse population screened for
      hemochromatosis: results from the Hemochromatosis and Iron Overload Screening
      (HEIRS) study.
AB  - PURPOSE: The HEIRS Study screened 101,168 primary care participants for iron
      overload with serum transferrin saturation (TS), serum ferritin (SF), and C282Y
      and H63D mutations of the HFE gene. The objective of this study was to evaluate
      the impact of screening on participants' well-being. METHODS: All C282Y
      homozygotes, participants with an elevated TS and SF concentration, and a control
      group of phenotype-genotype negative persons, with neither C282Y nor H63D
      mutations in the HFE gene were recalled for a clinical evaluation. Health-related
      quality of life was assessed before screening and approximately 1 week after
      receipt of the results. Health worries were assessed only at follow-up. RESULTS:
      Participants (N = 1478) completed both initial and follow-up surveys. After
      adjusting for model covariates, phenotype and genotype combinations were
      statistically significant predictors of changes in psychological well-being (P =
      0.0001) and general health (P = 0.0014). C282Y homozygotes with transient
      elevations in TS or SF were significantly more likely to worry about their health
      compared to study controls. Race, ethnicity, and preferred language subgroups
      differed on psychological well-being, general health, and health worry.
      CONCLUSION: Iron phenotype and HFE genotype are associated with health-related
      quality of life. Health worry was greatest among those considered genetically "at
      risk. " This may have important implications for multi-ethnic population-based
      screening studies in which genotype and phenotype are communicated.

PMID- 18073585
TI  - Utilization trends of genetic clinics excluding prenatal services in Washington
      State, 1995-2004.
AB  - PURPOSE: To analyze genetic clinic utilization in Washington State and to explore
      factors associated with utilization. METHODS: Our analysis included data from the
      9 of 15 genetic clinics that consistently reported to the Washington State
      Minimum Data Set between 1995 and 2004. Prenatal genetics services were excluded.
      We described utilization with yearly counts of patients and analyze patient
      volume according to age, sex, and residence. RESULTS: The total number of
      patients at nine genetic clinics in Washington increased from 1804 patients in
      1995 to 3536 patients in 2004 with growth increasing at an average 8% each year.
      Although adults aged 35 years and over comprised 14% of all patients in 1995,
      they comprised almost 28% in 2004. The number of females aged 35 years and older
      increased markedly during this time frame. CONCLUSION: Nine genetic clinics in
      Washington experienced growth in utilization and changes in the mix of patients
      served between 1995 and 2004. We suggest further study of how test availability,
      public awareness of genetics, supply of genetics providers, and changing
      regulations and insurance policies influence utilization of genetics clinics.

PMID- 18073586
TI  - Development of genomic reference materials for Huntington disease genetic
      testing.
AB  - PURPOSE: Diagnostic and predictive testing for Huntington disease requires an
      accurate measurement of CAG repeats in the HD (IT15) gene. However, precise
      repeat sizing can be technically challenging, and is complicated by the lack of
      quality control and reference materials (RM). The aim of this study was to
      characterize genomic DNA from 14 Huntington cell lines available from the
      National Institute of General Medical Sciences Human Genetic Cell Repository at
      the Coriell Cell Repositories for use as reference materials for CAG repeat
      sizing. METHODS: Fourteen Huntington cell lines were selected for study. The
      alleles in these materials represent a large range of sizes that include
      important diagnostic cutoffs and allele combinations. The allele measurement
      study was conducted by ten volunteer laboratories using a variety of polymerase
      chain reaction-based in-house developed methods and by DNA sequence analysis.
      RESULTS: The Huntington alleles in the 14 genomic DNA samples range in size from
      15 to 100 CAG repeats. There was good agreement among the ten laboratories, and
      thus, the 95% confidence interval was small for each measurement. The allele size
      determined by DNA sequence analysis agreed with the laboratory developed tests.
      CONCLUSION: These DNA materials, which are available from Coriell Cell
      Repositories, will facilitate accurate and reliable Huntington genetic testing.

PMID- 18073587
TI  - New at GeneTests.

PMID- 18073588
TI  - Complete absence of the pericardium in a patient with multiple injuries.

PMID- 18073589
TI  - Post-traumatic myocardial infarction complicated with left ventricular aneurysm
      and pericardial effusion.

PMID- 18073590
TI  - Thyroid storm after blunt thyroid injury: a case report.

PMID- 18073591
TI  - Early hyperglycemia predicts multiple organ failure and mortality but not
      infection.
AB  - BACKGROUND: Previous studies attempting to characterize the association between
      early hyperglycemia (EH) and subsequent outcome have been performed without
      utilization of a strict glycemic control protocol. We sought to characterize the
      clinical outcomes associated with EH in a cohort of severely injured trauma
      patients, when a strict glycemic control protocol was used. METHODS: Data were
      obtained from a multicenter prospective cohort study evaluating clinical outcomes
      in blunt injured adults with hemorrhagic shock. Known diabetics and patients with
      isolated traumatic brain injury were excluded from the analysis. A strict
      glycemic protocol (target glucose, 80-110 mg/dL) was employed. Cox proportional
      hazard regression was used to evaluate the effects of EH on multiple organ
      failure (MOF), nosocomial infection (NI), and mortality, after adjusting for the
      effects of early death on subsequent infection rates. RESULTS: Overall mortality,
      MOF, and NI rates for the entire cohort were 19.6%, 37.5%, and 42.2%,
      respectively, with a mean Injury Severity Score of 31.6 +/- 14. Cox proportional
      hazard regression confirmed that EH was independently associated with almost a
      twofold higher mortality rate and a 30% higher incidence of MOF, but was not an
      independent risk factor for NI, after controlling for all important confounders.
      There continued to be no independent association between EH and NI, even when
      stratified by infection type (pneumonia, catheter-related blood stream infection,
      or urinary tract infection). CONCLUSION: These results suggest that EH is a
      marker of severe physiologic insult after injury, and that strict glycemic
      control may reduce or prevent the infectious complications previously shown to be
      associated with hyperglycemia early after injury.

PMID- 18073592
TI  - Intensivist bedside ultrasound (INBU) for volume assessment in the intensive care
      unit: a pilot study.
AB  - BACKGROUND: Estimation of volume status in the high-acuity surgical population
      can be challenging. The use of intensivist bedside ultrasound (INBU) to rapidly
      assess volume status in the surgical intensive care unit (SICU) was hypothesized
      to be feasible and as accurate as invasive measures. METHODS: Clinician
      sonographers (CSs) were trained to perform basic cardiac ultrasound and
      sonographic assessment of the inferior vena cava (IVC). A convenience sample of
      general surgery and trauma patients was enrolled in the SICU. The CS interpreted
      IVC and cardiac parameters and then categorized the subject as hypovolemic or not
      hypovolemic. Intensivists caring for the patients were blinded to the INBU
      findings and made a real-time expert clinical judgment (ECJ) of the patient's
      volume status (hypovolemic vs. not hypovolemic) using all available traditional
      data. RESULTS: A total of nine CSs performed 70 studies; three of the CSs
      performed the majority of the studies (86%). Adequate ultrasound (US) views for
      cardiac and IVC assessment were obtained in 96% and 89% of studies, respectively.
      The ECJ was considered to be the standard to which comparisons were made. The
      concordance rate between ECJ and central venous pressure was 62%. ECJ concordance
      with sonographic measures were similar (cardiac US = 75%, IVC US = 67%, and IVC
      collapse index = 65%). All pairwise comparisons against the ECJ/CVP agreement
      were not significantly different. CONCLUSIONS: INBU is feasible in the SICU and
      is equivalent to central venous pressure in assessing volume status. Noninvasive
      methods to assess volume status may decrease the need for invasive procedures.

PMID- 18073593
TI  - Beta-blocker exposure in patients with severe traumatic brain injury (TBI) and
      cardiac uncoupling.
AB  - BACKGROUND: Cardiac uncoupling and reduced heart rate (HR) variability are
      associated with increased mortality after severe traumatic brain injury (TBI).
      Recent data has shown beta-blocker (betaB) exposure is associated with improved
      survival in this patient population. The purpose of the present study was to
      evaluate the effect of betaB exposure on the mortality risk of patients with
      severe TBI and early cardiac uncoupling. METHODS: From December 2000 to October
      2005, 4,116 patients were admitted to the trauma intensive care unit. Four
      hundred forty-six patients (12%) had head Abbreviated Injury Scale score >/= 5
      without neck injury and had continuous HR data for the first 24 hours. One
      hundred forty-one patients (29%) received betaB. Cardiac uncoupling was
      calculated as the percent of time that 5-minute HR standard deviation was between
      0.3 bpm and 0.6 bpm on postinjury day 1. RESULTS: A relationship between betaB
      and survival was observed when the population was considered irrespective of
      length of stay or betaB start time (p < 0.001). Cardiac uncoupling appears to
      stratify patients into groups who might receive additional benefit from betaB,
      and identifies patients with increasing mortality. However, the association of
      betaB with survival was attenuated when analyses accounted for selection bias in
      betaB administration. CONCLUSIONS: betaB exposure was associated with reduced
      mortality among patients with severe TBI. Though loss of HR variability has
      previously been associated with an increase in mortality, betaB exposure appears
      to be associated with increased survival across all stratifications of cardiac
      uncoupling.

PMID- 18073594
TI  - Prehospital loss of R-to-R interval complexity is associated with mortality in
      trauma patients.
AB  - BACKGROUND: To improve our ability to identify physiologic deterioration caused
      by critical injury, we applied nonlinear analysis to the R-to-R interval (RRI) of
      the electrocardiogram of prehospital trauma patients. METHODS: Ectopy-free, 800
      beat sections of electrocardiogram from 31 patients were identified. Twenty
      patients survived (S) and 11 died (NonS) after hospital admission. Demographic
      data, heart rate, blood pressure, field Glasgow Coma Scale (GCS) score, and
      survival times were recorded. RRI complexity was assessed via nonlinear
      statistics, which quantify entropy or fractal properties. RESULTS: Age and field
      heart rate and blood pressure were not different between groups. Mean survival
      time (NonS) was 129 hours +/- 62 hours. NonS had a lower GCS score (8.6 +/- 1.7
      vs. 13.2 +/- 0.8, p < 0.05). RRI approximate entropy (ApEn; 0.87 +/- 0.06 vs.
      1.09 +/- 0.07, p < 0.01), sample entropy (SampEn; 0.80 +/- 0.08 vs. 1.10 +/-
      0.05, p < 0.01) and fractal dimension by dispersion analysis (1.08 +/- 0.02 vs.
      1.13 +/- 0.01, p < 0.05) were lower in NonS. Distribution of symbol 2 (Dis_2), a
      symbol-dynamics measure of RRI distribution, was higher in NonS (292.6 +/- 34.4
      vs. 222 +/- 21.3, p < 0.10). For RRI data, logistic regression analysis revealed
      ApEn and Dis_2 as independent predictors of mortality (area under the receiver
      operating characteristic curve = 0.96). When GCSMOTOR was considered, it replaced
      Dis_2 whereas ApEn was retained (area under curve = 0.92). When Injury Severity
      Score was considered, it replaced GCSMOTOR; ApEn was retained. CONCLUSIONS:
      Prehospital loss of RRI complexity, as evidenced by decreased entropy, was
      associated with mortality in trauma patients independent of GCS score or Injury
      Severity Score.

PMID- 18073595
TI  - Use of long-term anticoagulation is associated with traumatic intracranial
      hemorrhage and subsequent mortality in elderly patients hospitalized after falls:
      analysis of the New York State Administrative Database.
AB  - BACKGROUND: Previous studies addressing the relationship between anticoagulation
      and risk of traumatic intracranial hemorrhage (ICH) have provided conflicting
      results, and have examined infrequently elderly patients after falls. We used a
      statewide hospital discharge database to test the hypothesis that long-term
      anticoagulation (LTA) increases the likelihood of traumatic ICH and subsequent
      mortality in this patient population. METHODS: Patients aged 65 years or older
      and hospitalized as the result of a fall were extracted from the New York State
      Statewide Planning and Cooperative Systems Database for the year 2004. LTA, ICH,
      and additional injuries including skull fracture, vertebral fracture, rib
      fracture, lower extremity fracture, thoracic visceral injury, and abdominal
      visceral injury were defined using corresponding International Classification for
      Disease, Ninth Edition coding. Covariates included age, gender, and comorbidity.
      Additional outcomes included length of stay and mortality. Multivariable logistic
      regression was used to identify independent predictors of traumatic ICH and
      subsequent mortality. RESULTS: A total of 47,717 patients met the inclusion
      criteria. Falls were associated with a traumatic ICH in 2,517 patients (5.1%),
      and the mortality rate of patients with a fall-related, traumatic ICH was 15.5%
      (n = 394). A total of 1,511 (3.2%) patients hospitalized after a fall used LTA.
      Based on univariate analysis, ICH was the only injury that occurred more commonly
      in patients who used LTA, when compared with those who did not (8.0% vs. 5.3%,
      respectively, p < 0.0001). Furthermore, although overall mortality did not differ
      by use of LTA, mortality after ICH was significantly higher in patients who used
      LTA when compared with those who did not (21.9% vs. 15.2%, respectively, p =
      0.04). Controlling for age, gender, and comorbidity, patients on LTA were 50%
      more likely to sustain a traumatic ICH after a fall (odds ratio = 1.50; 95%
      confidence interval, 1.23-1.81; p < 0.0001). Furthermore, among patients who
      sustained an ICH, mortality was 1.57-fold greater in patients on LTA (odds ratio
      = 1.57; 95% confidence interval, 1.02-2.45; p = 0.04). CONCLUSIONS: These data
      indicate that use of LTA is independently associated with traumatic ICH and
      subsequent mortality in elderly patients hospitalized after a fall.

PMID- 18073597
TI  - The scourge of methamphetamine: impact on a level I trauma center.
AB  - BACKGROUND: Methamphetamine (METH) use is associated with high-risk behavior and
      serious injury. The aim of this study was to assess the impact of METH use in
      trauma patients on a Level I trauma center to guide prevention efforts. METHODS:
      A retrospective registry-based review of 4,932 consecutive trauma patients who
      underwent toxicology screening at our center during a 3-year period (2003-2005).
      This sample represented 76% of all trauma patients seen during this interval.
      RESULTS: From the first half of 2003 to the second half of 2005, overall use of
      METH increased 70% (p < 0.001), surpassing marijuana as the most common illicit
      drug used by the trauma population. Other illicit drug use did not significantly
      change during this interval. METH-positive patients were more likely to have a
      violent mechanism of injury (47.3% vs. 26.3%, p < 0.001), with 33% more assaults
      (p < 0.01), 96% more gunshot wounds (p < 0.001), and 158% more stab wounds (p <
      0.001). They were more likely to have attempted suicide (4.8% vs. 2.6%, p <
      0.01), to have had an altercation with law enforcement (1.8% vs. 0.3%, p <
      0.001), or been the victim of domestic violence (4.4% vs. 2.1%, p < 0.001). METH
      users had a higher mean Injury Severity Score (11.2 vs. 10.0, p < 0.01), were 62%
      more likely to receive mechanical ventilation (p < 0.001), and 53% more likely to
      undergo an operation (p < 0.001). They were more prone to leave against medical
      advice (4.9% vs. 2.1%, p < 0.001) and 113% more likely to die from their injuries
      (6.4% vs. 3.0%, p < 0.001). The average cost of care per METH user was 9% higher
      than that for nonusers, and METH users were more likely to be unfunded than
      nonusers (47.6% vs. 23.1%, p < 0.001). The annual uncompensated cost of care of
      METH users increased 70% during the study period to $1,477,108 in 2005.
      CONCLUSION: METH use in trauma patients increased significantly and was
      associated with adverse outcomes and a significant financial burden on our trauma
      center. Evidence-based prevention efforts must be a priority for trauma centers
      to help stop the scourge of METH.

PMID- 18073596
TI  - Degree of anticoagulation, but not warfarin use itself, predicts adverse outcomes
      after traumatic brain injury in elderly trauma patients.
AB  - BACKGROUND: The relationship between preinjury warfarin use and outcomes after
      traumatic brain injury in elderly trauma patients remains controversial. We
      hypothesized that, among elderly warfarin users, the degree of anticoagulation,
      rather than warfarin therapy itself, would predict the severity of traumatic
      brain injury. METHODS: Retrospective study (2004-2006) of all elderly trauma
      patients (age >/=65 years) who were evaluated by the trauma service at a Level I
      trauma center and underwent computed tomography of the head for suspicion of an
      intracranial injury was performed. Three cohorts were grouped: (1) warfarin users
      with an admission International Normalized Ratio >/=2 (therapeutic group), (2)
      warfarin users with an admission International Normalized Ratio <2
      (nontherapeutic group), and (3) warfarin nonusers. Main outcome variables were
      presenting with a Glasgow Coma Scale (GCS) score </=13 points, intracranial
      hemorrhage (ICH), overall mortality, and mortality after ICH. RESULTS: A total of
      225 trauma patients were studied, including 40 warfarin users (17.3%), of whom 22
      (55.0%) were in the therapeutic group. Age, gender, and mechanism of injury were
      similar among groups. Likelihood of Glasgow Coma Scale score </=13 (odds ratio
      [OR] = 5.13, 95% confidence interval [CI] 1.97-13.39, p = 0.001), ICH (OR = 2.59,
      95% CI 0.92-7.32, p = 0.07), overall mortality (OR = 4.48, 95% CI 1.60-12.50, p =
      0.004), and mortality after ICH (OR = 3.42, 95% CI 1.09-10.76, p = 0.03) was
      increased in the therapeutic as compared with the nonuser group. There was no
      difference in any measured outcome between the nonuser and nontherapeutic groups.
      CONCLUSIONS: Therapeutic anticoagulation with warfarin, rather than warfarin use
      itself, is associated with adverse outcomes after traumatic brain injury in
      elderly patients.

PMID- 18073598
TI  - Accuracy of computed tomography (CT) scan in the detection of penetrating
      diaphragm injury.
AB  - BACKGROUND: The use of computed tomography (CT) to identify injury after
      penetrating torso trauma has become routine in the hemodynamically stable
      patient. The diaphragm has been a historically difficult structure to evaluate,
      however, and missed injuries to the diaphragm may result in significant
      morbidity. With the increasing use of multidetector row CT (MDCT), we
      hypothesized that CT would be an accurate detection modality to identify patients
      with diaphragm injuries. METHODS: We retrospectively reviewed the admission CT of
      consecutive patients admitted for penetrating injury to the torso during a 4-year
      period. The CT scans were reviewed and classified into three categories: positive
      (P), negative (N), or equivocal (Eq). Data from the medical records of these
      patients were abstracted to identify demographics, injury-specific data, length
      of stay, length of follow-up (LOFU), and operative findings. RESULTS: There were
      803 patients who met inclusion criteria. Mechanism of injury was gunshot wound in
      36% and stab wound in 64%. Mean length of stay was 4 days (+/-6.6) and mean
      length of follow-up was 43 days (+/-184). CT was read as P in 57, N in 710, and
      Eq in 36 patients. Diaphragm injury was detected in 67 patients overall and was
      excluded in 736. For the entire study population, sensitivity and specificity
      were calculated as 94.0% (95% CI = 88.4-99.7) and 95.9% (94.5-97.4) with an
      overall accuracy of 95.8% (94.4-97.2) if the CT scan was used to exclude
      diaphragm injury ([P and Eq] vs. N). Sensitivity and specificity were 82.1% (72.9
      91.3) and 99.7% (99.4-100) if CT was used to detect diaphragm injury (P vs. [N
      and Eq]). One hundred and forty-eight patients underwent operative procedures in
      which the diaphragm was evaluated. Diaphragm injury was identified in 50 (38 P, 4
      N, 8 Eq) and was surgically excluded in 104 patients (2 P, 93 N, 9 Eq). Three
      hundred and eighty-four patients were lost to follow-up; including 348 who had
      negative finding on CT. There were no known missed diaphragm injuries during the
      study period or in follow-up. CONCLUSIONS: Injuries to the diaphragm occur
      commonly after penetrating torso trauma. MDCT scan is an accurate test to detect
      diaphragm injury. When MDCT is equivocal, further investigation is required to
      evaluate the diaphragm.

PMID- 18073599
TI  - Is magnetic resonance imaging essential in clearing the cervical spine in
      obtunded patients with blunt trauma?
AB  - BACKGROUND: The optimal method of clearing the cervical spine (CS) in obtunded
      blunt trauma patients (OBTPs) remains unclear. Computed tomography (CT)
      identifies most injuries but may fail to detect ligamentous and spinal cord
      injuries. Magnetic resonance (MR) imaging has been widely used to exclude these.
      The purpose of this study was to evaluate whether CT of the CS (CT-CS) alone is
      adequate to clear the CS in OBTPs. Our hypothesis was that MR imaging of the CS
      (MR-CS) does not contribute relevant information and is not necessary in this
      patient population. METHODS: A prospective evaluation of OBTPs with a CT-CS
      negative for acute trauma and an MR-CS obtained for clearance was performed at a
      Level I trauma center between July 1, 2004, and June 30, 2006. Data gathered
      included demographics, results of CT-CS and MR-CS, timing of MR-CS, Glasgow Coma
      Scale score at time of MR-CS, adverse events occurring while obtaining MR-CS, and
      cervical collar complications. RESULTS: One hundred and fifteen patients were
      identified. There were 90 male patients. The mean age was 43.9 years +/- 1.9
      years, mean Injury Severity Score was 24.4 +/- 1.0, and mean length of stay was
      23.4 days +/- 1.2 days. The MR-CS was performed on hospital day 7.5 +/- 0.6 and
      the mean Glasgow Coma Scale score at the time of MR-CS was 8.3 +/- 0.3. Six MR-CS
      (5.2%) subsequently identified acute injuries. Findings included microtrabecular
      injuries, intraspinous ligament injuries, a cord signal abnormality, and a
      cervical epidural hematoma. None of these findings changed management and none
      required continued cervical collar usage. Six cervical collar complications were
      identified (5.2%). No adverse events related to transport or obtaining MR-CS
      occurred. Eliminating MR-CS would have decreased health care costs by over
      $250,000 during this period. CONCLUSIONS: MR-CS may be unnecessary in the OBTP if
      the CT-CS is negative. Elimination of MR-CS in this population will lead to
      earlier removal of cervical collars, decreased cervical collar complications,
      protection of the patient from exposure to potential risks inherent to obtaining
      this study, and decreased health care costs.

PMID- 18073600
TI  - Pregnancy is not a sufficient indicator for trauma team activation.
AB  - BACKGROUND: Trauma complicates 6% to 7% of all pregnancies. Adverse outcomes are
      rare when monitoring is normal and early warning signs absent. Trauma systems
      often use pregnancy as the sole criterion (PSC) for partial trauma team
      activation. This study compares outcomes of pregnant patients presenting with PSC
      versus other physiologic, mechanistic, or anatomic (OPMA) activation criteria.
      METHODS: Three hundred fifty-two consecutive obstetric partial trauma team
      activation patients (2000-2005) were grouped by length of gestation and evaluated
      for activation criteria and early maternal and fetal outcomes. Data were analyzed
      using descriptive statistics and analysis of variance. RESULTS: Patients ranged
      in age from 16 to 44 (mean age, 28 +/- 6.4) and in weeks gestation between 1 and
      40 weeks (mean, 25 +/- 8 weeks). Eighty-two percent had been in vehicle crashes.
      One hundred eighty-eight (58%) were activated based on PSC and 137 on OPMA. No
      PSC patient had injuries sufficient to warrant trauma service admission. Ninety
      four percent of all PSCs of <20 weeks were discharged home from the emergency
      department. There were no maternal mortalities. There were four fetal
      mortalities; two pregnancies were terminally compromised before the trauma event.
      No patient in the PSC group required admission to the trauma service. There were
      seven cases of abruption (2%) and 18 cases of vaginal bleeding or discharge (6%).
      No case of vaginal bleeding or abruption in the first 20 weeks was hypotensive at
      the scene or on arrival. CONCLUSION: In this study, pregnancy was not an
      independent predictor of the need for trauma team activation. Standard OPMA
      trauma activation criteria apply equally to pregnant and nonpregnant patients.
      These data provide support for more judicious allocation of scarce trauma systems
      resources.

PMID- 18073601
TI  - The use of "war games" to evaluate performance of students and residents in basic
      clinical scenarios: a disturbing analysis.
AB  - BACKGROUND: "Failure to Rescue" is a term applied to clinical issues that, if
      unrecognized or improperly treated, lead to adverse outcomes. We examined the
      cognitive components of rescue through the use of a "War Games" simulator format.
      Our hypothesis was that junior and senior medical students would be less able
      than interns and residents to detail the actions needed to assess, intervene, and
      stabilize patients. METHODS: Medical students and residents rotating on the
      trauma and surgical intensive care unit service participated. Twelve scenarios
      were created to focus on basic floor emergencies. Scores were assigned for
      clinical actions ordered. The scenarios were validated by two critical care
      attending physicians, and these scores were used as the expert group. Scores were
      assigned by two examiners, and the average of the grades in each area was used.
      The scores are a ratio of actual to possible correct responses in each section,
      and in the entire exercise. RESULTS: Subjects were divided into third-year
      medical students (MS3), fourth-year students (MS4), first-year residents (PGY1),
      residents beyond their first year (PGY2+), and experts. There were 20 subjects
      and 5 experts (n = 85) in each group for a total of 140 simulated cases examined.
      On initial evaluation, MS4 and PGY2+ performed significantly worse than expert,
      and MS3 and PGY1 performed similarly to experts. On secondary evaluation, all
      groups performed significantly worse than the expert group. In determining the
      diagnosis, only MS3 differed significantly from the experts. On follow-up, and in
      total score, all performed significantly worse than the experts. DISCUSSION: All
      groups had significant deficits in cognitive performance compared with experts in
      the areas of secondary evaluation, follow-up of the presenting problem, and total
      performance in simple clinical scenarios. We must design educational systems that
      rapidly enhance the cognitive performance of students and residents before they
      are left to independently diagnose and intervene in life-threatening clinical
      situations.

PMID- 18073602
TI  - Histidine inhibits the degradation of cells suspended in Ringer's lactate.
AB  - BACKGROUND: We previously demonstrated that the degradation of a suspension of
      Jurkat cells in Ringer's lactate (RL) was inhibited by the addition of a 4-(2
      hydroxyethyl)-1-piperazineethanesulfonic acid/Tris buffer. Given the ability of
      histidine to buffer protons in the physiologic range (pKa = 6.0), we hypothesized
      that this amino acid would have the same effect. METHODS: RL was made in our
      laboratory using sodium l-lactate. Jurkat cells were suspended in RL alone or RL
      with various concentrations of histidine or other test reagents at 37 degrees C
      for 4 hours or 24 hours in an atmosphere of 95% air and 5% CO2. Using flow
      cytometry, we measured cell shrinkage, phosphatidylserine translocation,
      propidium iodide uptake, and intracellular oxygen free radical production.
      RESULTS: Cell shrinkage was induced by suspension in RL after 4 hours incubation.
      At 4 hours, cell shrinkage was inhibited by all concentrations of histidine
      tested, 7.8 mumol/L to 10 mmol/L. There was no statistical difference between
      cells suspended in medium and cells suspended in 1 mmol/L or 10 mmol/L histidine.
      After 24 hours incubation, 100% of the cells in RL had undergone cell shrinkage
      whereas in 10 mmol/L histidine only a mean of 20% of the cells had undergone cell
      shrinkage. The inhibitory effect of 1 mmol/L histidine at pH 7.4 was compared
      with that at pH 6.8. After 4 hours incubation, there was no difference. After 24
      hours incubation, the inhibitory effect at pH 7.4 was significantly greater that
      that at pH 6.8. Histidine at 1 mmol/L to 10 mmol/L significantly reduced the
      percentage of cells that underwent phosphatidylserine translocation and propidium
      iodide uptake. The effect of the dipeptide buffer, glycylglycine, and the two
      other positively charged amino acids, arginine and lysine, after 4 hours
      incubation was compared with histidine at 1 mmol/L. At 1 mmol/L, histidine was
      superior to arginine and lysine and indistinguishable from glycylglycine.
      Intracellular free radical production was measured at 0.5 mmol/L, 1.0 mmol/L, and
      10 mmol/L histidine concentrations. There was significant inhibition only at 10
      mmol/L. CONCLUSIONS: Characteristics of apoptotic cell death that occur in cells
      suspended in RL are inhibited by the addition of histidine, arginine, and lysine
      as well as the dipeptide glycylglycine, which, with a pKa of 8.25, also buffers
      in the physiologic range. Histidine is superior to lysine and arginine at 1
      mmol/L. The salutary effect of histidine at 0.5 mmol/L and 1 mmol/L is caused by
      a mechanism other than the inhibition of oxygen free radicals. Moreover, the
      buffering of protons may play a role at 24 hours but made no difference at 4
      hours.

PMID- 18073603
TI  - Thresholded area over the curve of spectrometric tissue oxygen saturation as an
      indicator of volume resuscitability in porcine hemorrhagic shock.
AB  - BACKGROUND: A rapid, reliable, and noninvasive functional measure of
      responsiveness to resuscitation in posttraumatic hemorrhagic shock could prove
      useful in guiding therapy, especially under circumstances such as the battlefield
      and civilian mass casualties. Tissue oxygen saturation (Sto2) is a promising
      candidate for this application. We therefore explored the value of peripheral
      muscle Sto2 in predicting systemic responsiveness to colloid volume resuscitation
      in a porcine model of hemorrhagic shock. METHODS: Fourteen isoflurane
      anesthetized piglets were subjected to a standardized hemorrhage protocol that
      maintained mean arterial pressure (MAP) between 30 and 40 mm Hg. Asanguineous
      resuscitation with a volume of Hextend equal to the total volume bled was
      initiated when compensation was exhausted (MAP <30 mm Hg). We recorded continuous
      MAP and Sto2 values, and calculated the contiguous area over the Sto2 curve yet
      below a given threshold of Sto2 (TAOC) as a function of this threshold before the
      selected timepoint for timepoints up to 30 minutes before resuscitation. RESULTS:
      Hemorrhage resulted in significant fluctuations of MAP and high interindividual
      variability of disease dynamics and outcome: 4 nonsurvivors and 10 survivors at 2
      hours postresuscitation. Sto2 measurements reflected hemodynamic conditions in
      most animals, with a pronounced drop preceding final decompensation in 7 of 14
      animals. TAOC discriminated three of four nonresuscitable (nonsurvivor) animals
      from the survivors, with group differences reaching significance even for the
      earliest examined timepoint (30 minutes before resuscitation), depending on the
      choice of TAOC threshold. CONCLUSIONS: Sto2 may serve as a marker of
      decompensation, whereas TAOC, a physiologically motivated correlate of perfusion
      debt and cumulative hypoperfusion injury, may be a useful early indicator of
      responsiveness to volume resuscitation in hemorrhagic shock.

PMID- 18073604
TI  - Acute effects of TASER X26 discharges in a swine model.
AB  - BACKGROUND: Very little objective laboratory data are available describing the
      physiologic effects of stun guns or electromuscular incapacitation devices
      (EIDs). Unfortunately, there have been several hundred in-custody deaths, which
      have been temporally associated with the deployment of these devices. Most of the
      deaths have been attributed to specific cardiac and metabolic effects. We
      hypothesized that prolonged EID exposure in a model animal system would induce
      clinically significant metabolic acidosis and cardiovascular disturbances.
      METHODS: Using an Institutional Animal Care and Use Committee-approved protocol,
      11 standard pigs (6 experimentals and 5 sham controls) were anesthetized with
      ketamine and xylazine. The experimentals were exposed to two 40-second discharges
      from an EID (TASER X26, TASER Intl., Scottsdale, AZ) across the torso.
      Electrocardiograms, blood pressure, troponin I, blood gases, and electrolyte
      levels were obtained pre-exposure and at 5, 15, 30, and 60 minutes and 24, 48,
      and 72 hours postdischarge. p values <0.05 were considered significant. RESULTS:
      Two deaths were observed immediately after TASER exposure from acute onset
      ventricular fibrillation (VF). In surviving animals, heart rate was significantly
      increased and significant hypotension was noted. Acid-base status was
      dramatically affected by the TASER discharge at the 5-minute time point and
      throughout the 60-minute monitoring period. Five minutes postdischarge, central
      venous blood pH (6.86 +/- 0.07) decreased from baseline (7.45 +/- 0.02; p =
      0.0004). Pco2 (94.5 mm Hg +/- 14.8 mm Hg) was significantly increased from
      baseline (45.3 mm Hg +/- 2.6 mm Hg) and bicarbonate levels significantly
      decreased (15.7 mmol/L +/- 1.04 mmol/L) from baseline (30.4 mmol/L +/- 0.7
      mmol/L). A large, significant increase in lactate occurred postdischarge (22.1
      mmol/L +/- 1.5 mmol/L) from baseline (1.5 mmol/L +/- 0.3 mmol/L). All values
      returned to normal by 24 hours postdischarge in surviving animals. A minor,
      nonsignificant increase in troponin I was seen at 24 hours postdischarge (0.052
      ng/mL +/- 0.030 ng/mL, mean +/- SEM). CONCLUSIONS: Immediately after the
      discharge, two deaths occurred because of ventricular fibrillation. In this model
      of prolonged EID exposure, clinically significant acid-base and cardiovascular
      disturbances were clearly seen. The severe metabolic and respiratory acidosis
      seen here suggests the involvement of a primary cardiovascular mechanism.

PMID- 18073605
TI  - The protective effect of the blood brain barrier from systemic cytokines in an
      animal femur fracture model.
AB  - BACKGROUND: Previous studies of head trauma have shown profound release of
      cytokines in the brain. These changes were not expressed in peripheral tissues.
      The intent of this study was to take an animal model of femur fracture, monitor
      the expression of biochemical markers in the periphery, and compare this to their
      expression in the brain. METHODS: Rats were subjected to a weight-drop, femur
      fracture model, and then killed at various times. Samples of muscle, liver,
      serum, and brain were analyzed for concentrations of cytokines, and compared with
      controls. RESULTS: Statistically significant (p < 0.05) results from the study
      were found in the liver. Interleukin (IL)-2, IL-10, IL-11, and other acute phase
      reactants were elevated at 24 hours after injury, compared with in controls.
      Analysis of these cytokines in the brain showed no significant increase when
      compared with those of controls. Further analysis also demonstrated an increase
      in plasma C-reactive protein and leptin in the fracture group. These results
      differ from our previous brain trauma study, which demonstrated no increased
      expression of cytokines in liver or plasma. CONCLUSIONS: This animal model of
      peripheral injury demonstrates that there is a significant rise in acute phase
      reactants in liver tissue and plasma within 24 hours after injury, without a
      corresponding rise in cytokine concentration in the brain. These results suggest
      that although the brain is potentially exposed to the biochemical response to
      injury, the brain parenchyma itself is protected from up-regulation of
      proinflammatory cytokines. Interestingly, this is the opposite effect seen in our
      isolated brain injury study.

PMID- 18073606
TI  - Hematopoietic progenitor cells mobilize to the site of injury after trauma and
      hemorrhagic shock in rats.
AB  - BACKGROUND: Trauma and hemorrhagic shock (T/HS) has been demonstrated to result
      in bone marrow (BM) suppression and the release of hematopoietic progenitor cells
      (HPC) into the peripheral blood in both human beings and experimental animals.
      HPC have also been identified in numerous end organs after T/HS and the ongoing
      loss of progenitor cells from the BM may play a role in posttraumatic BM
      suppression. We investigated the hypothesis that HPC will specifically migrate to
      sites of tissue trauma and that this process is exacerbated by hemorrhagic shock
      (HS). METHODS: Sprague-Dawley rats (250-400 g) sustaining a unilateral lung
      contusion (LC) secondary to a blast wave of a percussive nail gun, were subjected
      to either HS (MAP 40-45 mm Hg for 45 minutes) or sham shock (SS). Animals were
      killed at 3 hours, 3 days, and 7 days after resuscitation and the right and left
      lungs from each animal were processed separately and the uninjured left lung
      served as a control for comparison with the contused right lung. BM mononuclear
      cells from each individual lung and the femurs were isolated and plated (2 x 10)
      in duplicate for granulocyte-macrophage colony-forming units (CFU-GM), erythroid
      colony-forming units (CFU-E), and erythroid burst-forming units (BFU-E) colony
      growth. RESULTS: At 3 hours, LC resulted in a significant increase in progenitor
      colonies able to be grown from the injured lung compared with from the uninjured
      lung (CFU-GM: 11 +/- 1 vs. 5 +/- 2, CFU-E: 12 +/- 7 vs. 5 +/- 3, BFU-E: 7 +/- 1
      vs. 3 +/- 1 colonies per 10 BM mononuclear cells; all p < 0.05). HS resulted in a
      significant increase of the number of colonies of all three cell types in both
      the uninjured and the contused lung (all p < 0.05). At day 3 after HS, BM
      progenitor growth remained suppressed whereas the number of cells recoverable
      from the lung returned toward baseline. By day 7, hematopoietic progenitor cell
      growth in the BM and the number of those cells able to be grown from the lung
      returned to levels observed in unmanipulated rats. CONCLUSION: Unilateral LC
      results in the rapid mobilization of a significant number of HPC from the BM to
      the site of injury. BM function is maintained under this condition. The addition
      of HS increases HPC mobilization from the BM and sequestration at the site of
      injury as well as decreasing BM HPC growth. We postulate that the accumulation of
      progenitor cells in the injured tissue combined with an alteration of normal BM
      homing, as exemplified by the decrease in progenitor cells from the lung without
      restoration of BM function, plays a role in posttraumatic BM suppression. The
      mechanism of shock-mediated mobilization from the BM and the exact role and fate
      of these cells at the site of injury requires further investigation.

PMID- 18073607
TI  - Inhibition of inducible nitric oxide synthase ameliorates lung injury in rats
      after gut ischemia-reperfusion.
AB  - BACKGROUND: Gut hypoperfusion is considered to be a critical event for organ
      failure during severe surgical insults. The mechanism of remote organ injury
      after intestinal ischemia-reperfusion (I/R) may involve the excessive nitric
      oxide (NO) production; however, its role has been controversial. We sought to
      determine whether a selective inducible NO synthase inhibitor, aminoguanidine
      (AG), ameliorates pulmonary microvascular injury after superior mesenteric artery
      occlusion. METHODS: Anesthetized rats underwent superior mesenteric artery
      occlusion for 30 minutes and reperfusion for 6 hours (I/R) or sham operation
      (control). Another set of animals undergoing I/R received an AG at the end of the
      ischemia. Pulmonary vascular permeability was assessed by measuring tissue
      retention of Evans Blue dye that binds albumin. The plasma was harvested and
      NO2/NO3 (end products of NO) was measured. The bacterial cultures of the
      mesenteric lymph node of animals were performed to estimate the gut bacterial
      translocation after injury. RESULTS: The concentration of NO2/NO3 of plasma in
      the I/R group was higher than that of the control (p < 0.05). The lung-to-plasma
      Evans Blue dye ratio in the I/R group was also higher than that of the control (p
      < 0.01). Treatment with the AG prevented this lung injury induced by the gut I/R.
      The incidences of gut translocation were not significantly different between the
      I/R and AG groups. CONCLUSIONS: Increased lung vascular permeability elicited by
      gut I/R was significantly attenuated with inhibition of an inducible NO release
      by AG. Control of bacterial translocation was not needed to prevent lung injury
      in this model.

PMID- 18073608
TI  - Pediatric blunt abdominal injury: age is irrelevant and delayed operation is not
      detrimental.
AB  - BACKGROUND: During the past 40 years, management of solid organ injury in
      pediatric trauma patients has shifted to highly successful nonoperative
      management. Our purpose was to characterize children requiring operative
      intervention. We hypothesized that older children would be more likely to require
      operative intervention. In particular, we wanted to examine potential outcome
      disparities between children who were operated upon immediately and those in whom
      attempted nonoperative management failed. Additionally, we asked whether
      attempted nonoperative management, when failed, put children at higher risk for
      mortality or morbidities such as increased blood product transfusions or lengths
      of stays. METHODS: Retrospective cohorts from seven Level I pediatric trauma
      centers were identified. Blunt splenic, hepatic, renal, or pancreatic injuries
      were documented in 2,944 children <1 to 19 years of age from January 1993 to
      December 2002. Data collected included demographics, hemodynamics, blood
      transfusions, Glasgow Coma Scale score, Injury Severity Score, hospital length of
      stay (LOS), intensive care unit (ICU) LOS, and mortality. Analysis involved 140
      (4.8%) of 2,944 patients requiring operation. Two cohorts were characterized: (1)
      immediate operation (IO), defined as laparotomy </=3 hours after arrival (n = 81;
      58%) and (2) failed nonoperative management (F-NOM), defined as laparotomy >3
      hours after arrival (n = 59; 42%). RESULTS: Comparing the two cohorts, no age
      differences were found. Compared with F-NOM, IO had significantly worse
      hemodynamics, Injury Severity Score, and Glasgow Coma Scale score and was
      associated with liver injuries. Pancreatic injuries were significantly associated
      with F-NOM. While controlling for injury severity to compare IO versus F-NOM,
      linear regression revealed equivalent blood transfusions, ICU LOS, hospital LOS,
      and mortality rates. CONCLUSION: IO and F-NOM are rare events and independent of
      age. When operated upon for appropriate physiology, the timing of operation in
      pediatric solid organ injury is irrelevant and not detrimental with respect to
      blood transfusion, mortality, ICU and hospital LOS, and resource utilization.

PMID- 18073609
TI  - Experience with splenic main coil embolization and significance of new or
      persistent pseudoaneurym: reembolize, operate, or observe.
AB  - BACKGROUND: To determine the need for further therapy in patients with persistent
      or new pseudoaneurysms (PSAs) after splenic main coil embolization. METHODS: The
      institutional review board approved the study. The study group consisted of 400
      hemodynamically stable patients (261 men, 139 women; mean age, 38.5 years) with
      blunt splenic injury. Abdominal computed tomography (ACT) images were assessed
      for grade of splenic injury, volume of hemoperitoneum, and evidence of splenic
      vascular injury including splenic vascular lesions and active bleeding. Splenic
      arteriography was performed for high-grade splenic injury and for ACT evidence of
      vascular injury. Follow-up ACT was reviewed for evidence of new or persistent
      PSAs after main coil embolization of the splenic artery. Medical records were
      reviewed to determine final outcome and any additional therapies used. RESULTS:
      Thirty-two patients had persistent (27) or new PSAs (5) after main coil
      embolization. Of these patients, two required splenectomy and one splenorrhaphy.
      The nonoperative salvage rate was 91% and the splenic salvage rate was 94%; this
      was comparable to the overall salvage rate of 95%. CONCLUSION: Splenic
      embolization remains a valuable adjunct in splenic salvage. Patients with
      persistent or new splenic PSAs after main coil embolization have similar splenic
      salvage rates to the overall cohort without additional therapies.

PMID- 18073610
TI  - Incidence of early pulmonary embolism after injury.
AB  - BACKGROUND: Pulmonary embolism (PE) is a well-recognized potentially fatal
      complication after trauma. PE is generally thought to occur days after the acute
      injury. Hypoxia early after injury is often ascribed to other causes. We
      hypothesized that PE often occurs early after injury and we sought to elucidate
      the timing of PE after trauma. METHODS: The trauma registry was used to identify
      all patients diagnosed with an acute PE between June 1999 and December 2004.
      Medical records were reviewed and demographics, injury specific data, length of
      stay, comorbidities, and mortality were recorded. Time from injury to diagnosis
      was recorded as was diagnostic modality and treatment. RESULTS: In total, 35,424
      patients were treated in our trauma center during the study period. Ninety-four
      patients with PE were identified (0.27%). Mean age was 45 (+/-18.5) years and
      mean Injury Severity Score was 23 (+/-11.4). Of the total patients, 82% were male
      and 91.6% sustained blunt trauma. Mean length of stay was 25 (+/-32.1) days.
      Anatomic areas injured included thorax (37%), lower leg/femur (38%),
      pelvis/acetabulum (22%), and spine (30%). The diagnosis was confirmed
      radiographically in 91 patients; two pulmonary emboli were confirmed at autopsy
      and one, despite a negative CT scan, was treated based on clinical suspicion. Of
      these 94 patients diagnosed with a PE, the PE was detected by angiogram in 5
      (5%), ventilation/perfusion scan in 10 (11%), and computed tomography scan in 76
      (81%). PE was diagnosed on day 1 to 4 in 35 patients (37%), on day 5 to 7 in 17
      patients (18%), on day 8 to 14 in 22 patients (23%), and after 14 days in 20
      patients (21%). Eleven percent died, but only two deaths were attributed to PE.
      CONCLUSION: PE remains relatively common after trauma and occurs in the absence
      of lower extremity or spinal fractures. Although PE is usually thought to occur
      between days 5 and 7 after injury, our data suggest that as many as 37% of
      pulmonary emboli occur early. Clinicians should consider PE in the differential
      for patients with unexplained hypoxia, even early after injury.

PMID- 18073611
TI  - The sensitivity of computed tomography (CT) scans in detecting trauma: are CT
      scans reliable enough for courtroom testimony?
AB  - BACKGROUND: Rapid and accurate recognition of traumatic injuries is extremely
      important in emergency room and surgical settings. Emergency departments depend
      on computed tomography (CT) scans to provide rapid, accurate injury assessment.
      We conducted an analysis of all traumatic deaths autopsied at the Bexar County
      Medical Examiner's Office in which perimortem medical imaging (CT scan) was
      performed to assess the reliability of the CT scan in detecting trauma with
      sufficient accuracy for courtroom testimony. METHODS: Cases were included in the
      study if an autopsy was conducted, a CT scan was performed within 24 hours before
      death, and there was no surgical intervention. Analysis was performed to assess
      the correlation between the autopsy and CT scan results. Sensitivity,
      specificity, positive predictive value, and negative predictive value were
      defined for the CT scan based on the autopsy results. RESULTS: The sensitivity of
      the CT scan ranged from 0% for cerebral lacerations, cervical vertebral body
      fractures, cardiac injury, and hollow viscus injury to 75% for liver injury.
      CONCLUSIONS: This study reveals that CT scans are an inadequate detection tool
      for forensic pathologists, where a definitive diagnosis is required, because they
      have a low level of accuracy in detecting traumatic injuries. CT scans may be
      adequate for clinicians in the emergency room setting, but are inadequate for
      courtroom testimony. If the evidence of trauma is based solely on CT scan
      reports, there is a high possibility of erroneous accusations, indictments, and
      convictions.

PMID- 18073612
TI  - Computed tomography for early and safe discontinuation of cervical spine
      immobilization in obtunded multiply injured patients.
AB  - BACKGROUND: Evaluation of the cervical spine (c-spine) in obtunded severely
      injured trauma patients is controversial, and spine immobilization is frequently
      prolonged. We examined the effect of two different c-spine evaluation protocols
      on c-spine immobilization and clinical outcomes. METHODS: We prospectively
      evaluated consecutive intubated and mechanically ventilated patients admitted to
      the surgical intensive care unit (ICU) of a Level I academic trauma center with a
      diagnosis of multiple blunt injuries who had normal findings on high-resolution
      helical computed tomogram of C1 to T1 with reconstructions (HCTrecon). From July
      1, 2003 to June 30, 2005 (n = 140), the findings of HCTrecon and either clinical
      examination or magnetic resonance imaging (MRI) were required to be normal to
      discontinue c-spine immobilization (clinical/MRI protocol). From July 1, 2005 to
      June 30, 2006 (n = 75), the policy was changed to require normal finding only on
      HCTrecon to discontinue c-spine immobilization (HCTrecon protocol). RESULTS:
      Patients evaluated by the clinical/MRI and HCTrecon protocols had similar
      baseline characteristics. Compared with clinical/MRI patients, HCTrecon patients
      had their c-spines immobilized for fewer days (median, 6 days vs. 2 days; p <
      0.001), were less likely to experience a complication of c-spine immobilization
      (64% vs. 37%, p = 0.010), required shorter periods of mechanical ventilation
      (median, 4 days vs. 3 days; p = 0.011), and had shorter stays in the ICU (median,
      6 days vs. 4 days; p = 0.028) and hospital (median, 16 days vs. 14 days; p =
      0.043). There was no difference in hospital mortality (13% vs. 16%, p = 0.920)
      and no missed c-spine injuries in either group. CONCLUSION: Discontinuation of c
      spine precautions based on the normal findings of HCTrecon decreases the duration
      of c-spine immobilization in obtunded severely injured patients and is associated
      with fewer complications, fewer days of mechanical ventilation, and shorter stays
      in the ICU and hospital.

PMID- 18073613
TI  - Magnetic resonance imaging is a useful adjunct in the evaluation of the cervical
      spine of injured patients.
AB  - BACKGROUND: Recognition of cervical spine (c-spine) injury is important to
      minimize the risk of disability. Yet the ideal method to detect injury remains
      controversial, especially in unexaminable patients. The purpose of this study was
      to evaluate the incidence of c-spine injury detected by magnetic resonance
      imaging (MRI) in patients with no abnormalities detected by computerized
      tomography (CT) scan and to determine whether the treatment plan was altered.
      MATERIALS: A retrospective study was performed on all patients who underwent both
      CT and MRI scanning of the c-spine in 2004 to 2005. Unexaminable patients formed
      a separate subgroup of the overall cohort. Patients were deemed to be
      unexaminable by the attending surgeon if their mental status remained depressed
      after intoxicants were judged to have been metabolized. CT and MRI scan findings
      were defined as normal if they were without any radiographic abnormality and
      showed only chronic degenerative changes. RESULTS: A total of 254 adult patients
      were included. Of these, 53 patients were unexaminable. Ninety patients showed
      abnormality on CT scan and were excluded from further analysis. MRI detected an
      injury in 42 of the remaining 164 patients whose CT scan disclosed nothing
      abnormal, 27 of which were ligamentous or cord injuries. The findings of the MRI
      resulted in surgery in 9, maintenance of the rigid cervical collar in 22, and
      discontinuance of the collar in 11 patients. In the unexaminable cohort, MRI
      detected an injury in 5 of 46 patients whose CT scan disclosed nothing abnormal,
      four of which were ligamentous and were treated by cervical collar
      immobilization. CONCLUSION: This study supports the practice of obtaining c-spine
      MRI in patients who are either unexaminable or symptomatic with the CT scan
      findings normal.

PMID- 18073614
TI  - Technical considerations in the operative management of femoral neck fractures in
      elderly patients: a multinational survey.
AB  - OBJECTIVE: To identify current opinions among orthopedic traumatologists relating
      to technical aspects of internal fixation and arthroplasty for patients with
      femoral neck fractures. METHODS: We developed and administered a survey to
      orthopedic surgeons who were members of the Orthopedic Trauma Association and
      European clinics affiliated with AO International (Davos, Switzerland). Surgeons
      reported preferences in specific aspects of the surgical technique for internal
      fixation as well as arthroplasty. Each surgeon received either a mailed package
      (7-page survey, a personalized cover letter, and a stamped return envelope) or an
      email with a link to the same survey on the Internet with an identification code.
      At 6 weeks, 12 weeks, and 18 weeks after the initial mailing, we remailed the
      questionnaire to all nonresponders. RESULTS: Of the 442 surgeons who were sent
      the questionnaire, 298 (68%) responded. The typical respondent was a North
      American aged more than 40 years, in academic practice, supervised residents, had
      fellowship training in trauma, and worked in a low-volume center. Among surgeons
      who treated displaced femoral neck fractures with arthroplasty, significant
      disparities existed in terms of the type of anesthesia (51% preferring general
      anesthesia), surgical approach (47% used posterior approach), and placement of
      unipolar implants (50%). Surgeons tended to agree on the use of cement fixation
      (69%), repairing the capsule (80%), and not using a drain postoperatively (68%).
      Surgeons who preferentially treated hip fractures with internal fixation tended
      to have a lack of consensus in terms of what constituted acceptable surgical
      delays (43% allowing greater than 48 hours) and which screw configuration to use,
      with more than half using a triangle with base inferior construct. Surgeons
      tended to agree on the use of closed fracture reduction techniques (69%), three
      cannulated screws (73%), and did not routinely perform a capsulotomy (80%) or
      aspirate the fracture hematoma (90%). Within both treatment groups (internal
      fixation and arthroplasty), surgeons tended to agree on the use of perioperative
      antibiotics (>92%), thromboprophylaxis (98%), and postoperative weight bearing
      status (>87%). CONCLUSIONS: A general lack of consensus exists among orthopedic
      trauma surgeons in the management of displaced femoral neck fractures. With an
      ever-growing emphasis upon the practice of evidence-based medicine, we have
      demonstrated several disparities in the technical aspects of fixation and
      perioperative care likely caused by a general lack of available evidence. We
      recommend the need for future research and large collaborative efforts.

PMID- 18073615
TI  - Resorbable fillers reduce stress risers from empty screw holes.
AB  - BACKGROUND: Empty screw holes after hardware removal are stress risers that
      weaken bone and can lead to refracture in an active individual. We sought to
      reduce these stress risers. We hypothesize that resorbable screws used as hole
      fillers would (1) provide immediate strength and (2) maintain this strength
      during resorption. METHODS: Randomized, prospective controlled animal laboratory
      study with 75 live New Zealand white rabbits' paired femurs. Single mid
      diaphyseal holes were filled with a metal or resorbable screw; contralateral
      femurs were paired empty hole controls. Main outcome measurements included
      histologic analysis, torsion to failure, peak torque, energy to failure, and
      stiffness at baseline, 1 week, and 13 weeks postimplantation. RESULTS: At time
      baseline, resorbable fillers produced an immediate 30% increase in the peak
      torque (p = 0.01) and 73% increase in peak energy (p = 0.006). Metal screws
      produced a 17% increase in peak torque (p = 0.038), and a 58% increase in the
      amount of energy to failure (p = 0.009). At 1 week, although the resorbable (p =
      0.01) but not the metal (p = 0.82) screws increased the peak torque, both metal
      (p = 0.003) and resorbable (p = 0.050) screws increased the peak energy compared
      with contralateral empty controls. At 13 weeks, metal and resorbable screw-filled
      bones were as strong as the healed contralateral femurs. Partial screw resorption
      and new bone formation without lysis was demonstrated histologically. Resorbable
      screw hole fillers immediately increase the strength of bones without weakening
      during early resorption. CONCLUSIONS: Placing resorbable fillers in bone defects
      after hardware removal could reduce the likelihood of refracture.

PMID- 18073616
TI  - Early experience and results of bone graft enriched with autologous platelet gel
      for recalcitrant nonunions of lower extremity.
AB  - BACKGROUND: Refractory nonunions of the tibia or femur are physically and
      mentally devastating conditions for the patients, and the treatment is
      challenging for orthopedic surgeons. The goal of this study was to assess the
      feasibility and outcome of surgical treatment in recalcitrant nonunions of a
      lower extremity with bone graft enriched with autologous platelet gel (APG).
      METHODS: Twelve patients with four femoral and eight tibial atrophic nonunions
      after multiple prior procedures were included. All of them were treated with the
      bone grafting procedures with autograft complex enriched with APG. They were
      evaluated with radiographs, bone mineral density for bony healing process, and
      the Short-Form 36 Health Survey for functional outcome. RESULTS: Of the 12
      patients, 11 healed at an average of 19.7 weeks after the first attempt and 1
      healed after the second attempt at 21 weeks. The bone mineral density continued
      to increase steadily from early healing to the remodeling phase. Functional
      status was greatly improved at an average follow-up of 32.4 months. CONCLUSIONS:
      The results of this preliminary study implied the possible potential of bone
      graft enriched with APG in the treatment of recalcitrant nonunions of the lower
      extremity. More research is necessary to clarify its role in augmentation of bone
      graft to enhance healing of nonunion.

PMID- 18073617
TI  - Androstenetriol immunomodulation improves survival in a severe trauma hemorrhage
      shock model.
AB  - BACKGROUND: Traumatic shock activates the hypothalamic-pituitary-adrenal axis
      (HPA) to mediate a cascade of defensive mechanisms that often include
      overwhelming inflammatory response and immunosuppression, which may lead to
      multiple organ failure. Androstenetriol (5 androstene, 3beta, 7beta, 17beta triol
      AET) is a metabolite of dehydroepiandrosterone that markedly up regulates host
      immune response, prevents immune suppression, modulates inflammation and improves
      survival after lethal infections by pathogens and lethal radiation. HYPOTHESIS:
      AET-induced immune modulation will improve survival in a conscious rodent model
      of traumatic shock. METHODS: A relevant traumatic shock rodent model that applies
      to both combat and civilian sectors was used. After creation of a midline
      laparotomy (soft tissue trauma), animals were hemorrhaged to a mean arterial
      pressure of 35-40 mm Hg. Resuscitation was initiated sixty minutes later with
      crystalloid fluid and packed red blood cells and animals were observed for two
      days. In a randomized and blinded fashion, AET or vehicle was administered
      subcutaneously at the beginning of resuscitation. RESULTS: In the vehicle group 5
      out of 16 animals survived, (31%). In contrast, 9 out of 13 animals who received
      AET survived (69%), (Fisher Exact Test p < 0.05). Survival in the AET treatment
      group was associated with reduced levels of IL-6, IL-10, and IL-18, and enhanced
      IFN-gamma and IL-2 levels. CONCLUSION: : The results indicate that AET provides a
      significant protective effect and improves survival in a clinically relevant
      model of traumatic hemorrhagic shock. AET protective effects are associated with
      an elevation of Th1 and reduction of Th2 cytokines.

PMID- 18073619
TI  - Availability of trauma specialists in level I and II trauma centers: a national
      survey.
AB  - BACKGROUND: Despite American College of Surgeons Committee on Trauma's criteria,
      little data exists about the variability of practices in both the composition of
      trauma teams and timing of specialist availability across trauma centers. The
      purpose of the study was to determine the availability of trauma team personnel
      in Level I and II trauma centers across the United States. METHODS: Two surveys
      were developed and mailed to trauma directors and coordinators in 450 centers.
      Responses were received from 254 directors (56%) and 218 coordinators (48%). The
      director survey was designed to collect data on trauma team composition and
      timeliness in response to a hypothetical scenario. The coordinator survey was
      designed to collect data on trauma center characteristics and general
      availability of trauma specialists. RESULTS: Eighty-two percent of Level I and II
      centers had trauma surgeons available within 15 minutes of and 37% at patient
      admission. The in-house (IH) centers (60%) had a trauma surgeon at patient
      admission significantly more than on-call centers did (22%). The specialty
      surgeons, such as neurosurgeons (73%) and orthopedic surgeons (75%), were mostly
      available through the on-call system. An IH system, high volumes of trauma
      patients, and designation by American College of Surgeons were significantly
      associated with higher likelihood of trauma surgeons physically present at the
      bedside within 15 minutes. CONCLUSIONS: There was a large variation in the
      availability of expertise at or shortly after a trauma admission. For centers
      with low patient volume, early triage, better notification systems based on
      advanced telecommunication technology, and compensation for IH call may be a
      solution to better use the trauma surgical specialties.

PMID- 18073618
TI  - Two cohorts of severely injured trauma patients, nearly two decades apart:
      unchanged mortality but improved quality of life despite higher age.
AB  - BACKGROUND: The care for trauma patients has undergone major changes during the
      last decades. Additionally, many injury prevention measures have been
      established. The objective of these efforts was to reduce the number of traumatic
      incidents and to reduce mortality and morbidity in injured patients. The aim of
      our study was to assess how these measures and improved care have altered trauma
      mechanisms, occurrence of injuries, treatment, and outcome in the trauma
      population treated at our trauma center. METHODS: Two cohorts of trauma patients
      with an Injury Severity Score >15, treated at the University Medical Center
      Groningen were compared. The first cohort was treated from 1985 to 1990, the
      second cohort from September 2002 to January 2005. RESULTS: The annual mean
      number of severely injured patients increased by 76%. Fourteen percent more
      patients had sustained an injury at home. The mean age increased from 33 +/- 22
      years to 41 +/- 23 years. The presence of severe head and neck injuries in the
      patients increased from 62% to 73%. Inhospital mortality remained unchanged at
      25%. The outcome of survivors improved; 67% of patients made a moderate or good
      recovery versus 40% almost 20 years ago. CONCLUSIONS: Striking are the
      consequences of the aging of the Dutch population: an almost 10-year increase in
      mean age and a rise in severe head and neck injuries in the population treated at
      our trauma center. The unchanged mortality and improved outcome of survivors
      represented the enhanced trauma care.

PMID- 18073620
TI  - Takotsubo syndrome in an elderly woman with blunt trauma.

PMID- 18073621
TI  - Neurogenic pulmonary edema caused by a medulla oblongata lesion after head
      trauma.

PMID- 18073622
TI  - Inflammation and the host response to injury, a large-scale collaborative
      project: patient-oriented research core-standard operating procedures for
      clinical care: VI. Blood glucose control in the critically ill trauma patient.

PMID- 18073623
TI  - Practice management guidelines for the screening of thoracolumbar spine fracture.
AB  - BACKGROUND: Fractures to the thoracolumbar spine (TLS) commonly occur because of
      major trauma mechanisms. In one series, 4.4% of all patients arriving at a Level
      I trauma center were diagnosed as having TLS fracture. Approximately 19% to 50%
      of these fractures in the TLS region will be associated with neurologic damage to
      the spinal cord. To date there are no randomized studies and only a few
      prospective studies specifically addressing the subject. The Eastern Association
      for the Surgery of Trauma organization Practice Management Guidelines committee
      set out to develop an EBM guideline for the diagnosis of TLS fractures. METHODS:
      A computerized search of the National Library of Medicine and the National
      Institutes of Health MEDLINE database was undertaken using the PubMed Entrez
      (www.pubmed.gov) interface. The primary search strategy was developed to retrieve
      English language articles focusing on diagnostic examination of potential TLS
      injury published between 1995 and March 2005. Articles were screened based on the
      following questions. (1) Does a patient who is awake, nonintoxicated, without
      distracting injuries require radiographic workup or a clinical examination only?
      (2) Does a patient with a distracting injury, altered mental status, or pain
      require radiographic examination? (3) Does the obtunded patient require
      radiographic examination? RESULTS: Sixty-nine articles were identified after the
      initial screening process, all of which dealt with blunt injury to the TLS, along
      with clinical, radiographic, fluoroscopic, and magnetic resonance imaging
      evaluation. From this group, 32 articles were selected. The reviewers identified
      27 articles that dealt with the initial evaluation of TLS injury after trauma.
      CONCLUSION: Computed tomography (CT) scan imaging of the bony spine has advanced
      with helical and currently multidetector images to allow reformatted axial
      collimation of images into two-dimensional and three-dimensional images. As a
      result, bony injuries to the TLS are commonly being identified. Most blunt trauma
      patients require CT to screen for other injuries. This has allowed the single
      admitting series of CT scans to also include screening for bony spine injuries.
      However, all of the publications fail to clearly define the criteria used to
      decide who gets radiographs or CT scans. No study has carefully conducted long
      term follow-up on all of their trauma patients to identify all cases of TLS
      injury missed in the acute setting.

PMID- 18073624
TI  - Emphysematous pyelonephritis.

PMID- 18073625
TI  - The treatment of refractory intracranial hypertension and its control by means of
      external lumbar drainage (ELD).

PMID- 18073626
TI  - Pyloric exclusion leads to a trend toward more complications, a higher pancreatic
      fistula rate, and a longer hospital length of stay.

PMID- 18073627
TI  - We recently received a 27-year-old female zoo worker who was attacked by a jaguar
      (Panthera onca) while cleaning its cage..

PMID- 18073628
TI  - Report on changes in thoracolumbar computed tomography (CT) and radiography use
      for trauma patients after deployment of multidetector CT in emergency rooms.

PMID- 18073633
TI  - Malnutrition: supplements and food fortification in the older population.
AB  - There is an important relationship between positive nutritional status, dietary
      intake and a healthy population. Lifelong adoption of healthy eating patterns is
      essential for life and can help reduce the risk of development of many illnesses.
      Malnutrition remains very prevalent in both developed and developing countries
      despite ongoing awareness campaigns. The consequences of malnutrition are broad
      ranging and ultimately impact on quality of life, increase length of stay in
      hospital and overall; increase the risk of unsuccessful outcomes of treatment.
      The management of malnutrition requires using appropriate screening tools to
      identify malnutrition and access to a registered dietician-who are the experts in
      nutrition-who will provide dietary advice to improve dietary intake through
      conventional dietary means and if unsuccessful through artificial
      supplementation. Failure to acknowledge the risks of malnutrition can seriously
      impact on morbidity and mortality rates.

PMID- 18073634
TI  - Older people who fall: why they matter and what you can do.
AB  - The population is ageing in all developing nations. As treatments and survival
      rates improve for conditions affecting younger people, age-related problems
      linked to frailty, functional impairment and long term conditions will pose an
      ever larger challenge to health and social care systems. Falls and associated
      injuries or loss of function are such a problem. Effective falls intervention
      strategies mean that primary care and community nursing must play a central role,
      as many patients will never present to hospital services, nor could hospital
      services cope--for instance one in three people over 65 will fall in a given year
      and one in two women will sustain a fracture during their lifetime. Fall and
      fracture prevention has, until the past few years, been a low priority in service
      delivery, training and research. However, its importance as a public health
      challenge has been increasingly recognized in government policy and in clinical
      guidelines, though we are still a long way off delivering evidence-based
      interventions and assessments to those who would benefit. There is plenty that
      clinicians can do to reduce the chance of further falls and injuries, to optimize
      patients' confidence and ability to cope and to use falls as a 'case-finding'
      trigger to address a host of other, often unrecognized problems. There is plenty
      community nurses can do in initial assessment, intervention and monitoring. This
      article sets out the key practice points and in particular the key sources of
      evidence for practice development.

PMID- 18073636
TI  - The complexities of managing breast oedema.
AB  - This article looks at the problems surrounding breast oedema and the complexities
      that surround this condition: the psychological impact, the distress that it
      causes, and the absolute need for appropriate referral to a specialist centre
      when it is diagnosed. There is a case study within this article which clearly
      identifies how painful the condition is, and how after conservative intervention,
      the patient feels relief and can resume living again.

PMID- 18073635
TI  - Managing diarrhoea in the home to prevent admission.
AB  - Many people with long term conditions wish to receive care at home or in the
      nursing home where they live. Sometimes if a person develops diarrhoea the
      clinician's first instinct is to transfer the person to hospital. The person who
      has severe diarrhoea may need hospitalisation, however many people, especially
      those who have indicated that their preferred place of care is home rather than
      hospital, can be managed effectively at home. Enabling the person to remain at
      home whenever possible empowers the person and enables carers, community nursing
      staff and nursing home staff to provide the best possible level of care.

PMID- 18073637
TI  - PCT Commissioning: how community nurse involvement can be encouraged.
AB  - Commissioning is the process by which PCTs identify the health needs of their
      population and make prioritized decisions to secure care to meet those needs
      within available resources. It includes longer term strategic planning, medium
      term planning (three year Local delivery Plans) and the shorter term agreement
      and performance management of service level agreements. The process should
      involve the public, engage clinicians, and be conducted on a whole system basis,
      informed by health equity audits, and carried through with the full participation
      of other stakeholders including NHS Trusts, local authority(s) and the voluntary
      sector (NHS Modernization Agency, 2004).

PMID- 18073638
TI  - Part 2: Defining the unique role of the specialist district nurse practitioner.
AB  - This is the second of a series of articles exploring the unique role of the
      district nurse. Case scenarios demonstrate the value of high quality care
      provided when delivering, home IV therapy, Catheterization, Medicine reviews,
      risk assessments, referrals and acting as the patients advocate.

PMID- 18073639
TI  - The new challenge: lifetime neighbourhoods.
AB  - Communities as we have known them are disintegrating, and traditional services
      are becoming dispersed or closed altogether. But rather than cry over spilt milk,
      local citizens must seize the opportunity (now offered by all parties) to
      seriously engage with all the public authorities and reshape the neighbourhoods
      in which they live.

PMID- 18073640
TI  - Understanding confidentiality and disclosure of patient information.
AB  - The need to share information about patients is vital to effective care and
      protection, especially where it relates to children or vulnerable adults.
      District nurses in common with other health professionals are often reluctant to
      share information because of a misunderstanding over the extent of their duty of
      confidence to patients. This has resulted in the needs of patients being unmet
      and in some cases tragic deaths have occurred. In this article Richard Griffith
      outlines the extent of the district nurses duty of confidence and considers when
      sharing patient information is lawful.

PMID- 18073641
TI  - Lessons from the Maidstone and Tunbridge tragedy.

PMID- 18073643
TI  - Defining the unique role of the specialist district nurse practitioner.
AB  - Due to the reorganization of primary care trusts across the country, certain
      trusts proposed a reduction in the specialist district nurse practitioner numbers
      in favour of less qualified community nurses and health care assistants. Such
      proposals in one PCT were blocked, partly in response to documentation compiled
      by practitioners at the sharp end of nursing practice. With the new agenda of
      practice based commissioning, it is imperative that commissioners and management
      alike are aware of the scope of specialist district nurse practitioners. This is
      the first of a series of articles looking at specific case histories where the
      role of the district nurse is highlighted. It is the intention to stress the
      importance of the clinical expertise and confidence required by the district
      nurse to care for patients with complex needs in the community.

PMID- 18073644
TI  - Constipation and flatulence management for stoma patients.
AB  - The ostomate (person with a stoma) has many issues to overcome when coming to
      terms with their new stoma. Some of the problems that can be associated with a
      colostomy are constipation and flatus. The ileostomate may also be troubled with
      flatulence. Causal factors for flatus may be ingested air or gut bacteria.
      Constipation may be a result of many factors, including diet and medication. The
      community nurse is in an ideal position to assist this patient group and this
      article offers a number of potential treatments or advice that the community
      nurse can provide for the ostomate. Many of the tips provided in this article are
      simple but may be potentially effective.

PMID- 18073645
TI  - Community matrons improve health: patients' perspectives.
AB  - Community matrons are integral to the government's plans to reduce hospital bed
      use by people with long-term conditions. Community matrons have been given the
      role of case managing the very high intensity users in an attempt to reduce
      emergency bed days through preventing admissions and early discharge and through
      working closely with their patients to develop personalized plans of care and to
      support and encourage patients to take more control of their condition. To date
      there has been little research from the patients' perspective into whether
      community matrons are achieving their aim. This series of two articles reports on
      an evaluation of a community matron service, which was initiated over two years
      ago, from the perspective of the patient. This second article reports on the
      patients' perspective on how the community matron's involvement has improved
      their health and what patients' perceived to be important about the community
      matron service. The findings indicate that patients' value the community matrons
      understanding of their individual experiences of long-term conditions; the
      clinical skills to address and give patients confidence that their conditions
      could be managed; and the availability of the community matrons to the patients.
      These aspects of the community matron's role seemed to help the patients to feel
      safe and secure, improved their quality of life and ultimately increased the
      confidence and control they felt over their long-term conditions.

PMID- 18073646
TI  - Delivering expert cardiac support in the community.
AB  - This article outlines how cardiac problems can be assessed in the primary care
      environment, improving patient care and helping alleviate some of the operational
      and financial burdens on secondary and emergency care providers. It examines the
      approach that Bridgwater Community Hospital took in monitoring and managing
      cardiac conditions within primary care. By opting for a cardiac telemedicine
      service, clinicians get fast, expert interpretation of ECG results, enabling them
      to deliver timely and more effective, preventative care, as well as delivering
      clear cost benefits across the trust, and ensuring healthcare resources are
      optimized.

PMID- 18073647
TI  - Will health trainers reduce inequalities in health?
AB  - The Health Trainer initiative was a public policy initiative designed to tackle
      health inequalities. Despite considerable improvements in the health of the
      population in the United Kingdom, there continues to be a gap between the rich
      and the poor in terms of deaths from cancer, stroke and coronary heart disease.
      There is a relationship between these health problems and lifestyle behaviours
      such as smoking, physical inactivity and poor diet. The Health Trainer initiative
      was created as part of the white paper Choosing Health. Following initial
      implementation across targeted Primary Care Trusts (The Spearhead Group), a
      rigorous evaluation of the initiative is taking place prior to a national roll
      out. This paper uses Whitehead's framework to examine the decision to implement
      health trainers as a stated aim of tackling health inequalities. The four
      purposes of health policy as identified by Whitehead (1995) and the categories of
      healthy living initiatives (Visram and Drinkwater 2005) are examined and applied
      to the health trainer initiative and its potential for reducing health
      inequality.

PMID- 18073648
TI  - Evaluation of the NMC community specialist practitioner award.
AB  - This paper discusses the evaluation of the NMC community specialist practitioner
      (CSP) programme over a period of four years. The purpose of the evaluation was to
      assess if the programme produced practitioners who were fit for purpose and fit
      for practice as well as assessing whether they were supported in their new roles.
      The evaluation took place eight months after qualification at a workshop where
      the practitioners discussed their experiences in focus groups. The evaluation is
      presented using Kirkpatrick's model and the results indicate the importance of
      collaboration between HEI's and their sponsors in meeting students' needs. Issues
      about support and work life balance are also highlighted as areas that were
      addressed as a result of the evaluation. Continued development of the programme
      through collaboration is desirable to produce effective practitioners who are
      able to function in the changing primary care arena.

PMID- 18073650
TI  - Legal requirements for the prescribing and administration of medicines.
AB  - On the 15th anniversary of the introduction of the Medicinal Products:
      Prescription by Nurses etc. Act 1992, Richard Griffith reflects on the
      development of nurse prescribing since the Acts implementation and outlines the
      current procedures by which district nurses may prescribe, supply or administer
      medicines to patients and the requirements that must be met in order to do so
      lawfully.

PMID- 18073649
TI  - Give consideration to financial abuse among the older population.
AB  - This article, brought to you in association with Help the Aged, considers
      financial exclusion, low levels of financial capability, and cognitive impairment
      among older people, which can lead to them becoming reliant on significant others
      to manage their finances.

PMID- 18073651
TI  - Where is the evidence?

PMID- 18073652
TI  - Childhood obesity--the 21st century epidemic.

PMID- 18073654
TI  - Requirements of the 'would be' nurse.

PMID- 18073653
TI  - A global perspective on cancer prevention.

PMID- 18073655
TI  - Under diagnosis of alcohol misuse in the older adult population.
AB  - Alcohol abuse in older adults is common, yet it is often under detected and
      misdiagnosed, and as a result associated with considerable morbidity. There is
      growing concern that as the population ages, there will be a substantial increase
      in the number of older adults needing treatment for alcohol misuse and currently,
      little is done to identify and address this situation. Factors contributing to
      under diagnosis include, but are not limited to, depression, dementia, physical
      changes associated with age, life events, late onset of alcoholism and lack of
      screening. A case report is presented and existing research findings are
      discussed. The importance of assessment, the use of screening tools, treatment
      issues and identification of other comorbidities are presented. The focus on
      increased awareness among clinicians as well as their role in identifying and
      addressing alcohol abuse issues in the older adult population is explored.

PMID- 18073656
TI  - High expressed emotion, severe mental illness and substance use disorder.
AB  - This article discusses the behavioural attitudes of high expressed emotion as a
      major contributor to relapse in patients dually diagnosed with severe mental
      illness and substance use disorder. There are a number of research studies and
      authoritative texts on this particular problem and discussions identify the role
      expressed emotion plays in this condition. However, the majority of literature
      concentrates on how high expressed emotion affects the person's mental illness
      causing relapse rather than any effect on their substance misuse. This article
      outlines severe mental illness and substance use disorder; identifies the
      components of expressed emotion and how this may contribute to relapse;
      management and care in this condition; the treatment and avoidance of expressed
      emotion by the family and the professional; and issues of nurse education,
      training and support.

PMID- 18073657
TI  - Altered living: coping, hope and quality of life after stroke.
AB  - This care study assesses how individuals who have had a stroke negotiate loss of
      functional abilities and disruption to life in order to achieve quality of life.
      Focusing on a particular individual in a rehabilitation ward, the article
      discusses how continued problem-solving and goal-setting is imperative to life
      satisfaction. However, this process is only possible when individuals feel that
      they have autonomy and mastery over their own existence, and so healthcare
      professionals must encourage them to make decisions about their care. By
      empowering individuals to do this they can achieve satisfaction by altering the
      values they ascribe to different areas of their lives.

PMID- 18073658
TI  - Section 5(4) of the Mental Health Act 1983: the art of applying the Act.
AB  - Section 5(4) of the Mental Health Act 1983 allows patients to be detained by
      nurses of the 'prescribed class' for a maximum of 6 hours. There is a paucity of
      research on the subject of Section 5(4); however, the little research that has
      been conducted has shown that there are gaps in the knowledge of registered
      nurses and nursing students due to be registered with regard to the following
      areas of Section 5(4): duration of the holding power; whether the client can be
      treated against their will; eligibility for detention; and criteria for
      implementation. This article will seek to clarify these gaps and provide nurses
      with a comprehensive systematic guide to follow should they have to invoke the
      section.

PMID- 18073659
TI  - Nursing attitudes towards recording of religious and spiritual data.
AB  - Poor recording of patients' religious and spiritual information is known
      anecdotally and occasionally referred to in publications. Chaplains in particular
      encounter lack of data entries or errors in records on a routine basis. While
      novel forms of spiritual assessment have been discussed, the only previously
      published United Kingdom research on nurses' responses to patients' spiritual
      needs uses the approach of critical incident analysis. This article reports on
      the findings of a nurse focus group used to generate issues likely to resonate
      with staff as to why poor assessment and recording occurs. Apart from clinical
      factors, nurses cited the intrusiveness of questions about spirituality and the
      feeling that assessment was 'unnecessary' as major reasons for non-recording. The
      most significant finding was the correlation between clinical area and the
      incidence of assessment. Nurses who admitted patients and always asked for
      religious and spiritual information were three times more likely to work in
      complex clinical areas. Further training is indicated as most likely to enhance
      accurate recording. More research is needed to establish whether these findings
      are matched in practice, and to identify whether the results found in one
      teaching hospital are equally true for other types of hospital in the UK.

PMID- 18073660
TI  - The Mental Capacity Act 2005: lasting power of attorney.
AB  - This article continues the series in analysing the implications of the Mental
      Capacity Act 2005 by looking at how a person (donor) is able to appoint another
      person (donee) to have the power to act on his or her behalf in relation to care
      and treatment decisions. Section 9 of the Act explicates that a donee has the
      authority to make decisions about the donor's personal welfare or specific
      matters concerning the donor's personal welfare, as well as the donor's property
      or affairs or specific matters concerning his or her property or affairs. This
      article examines the details regarding these new provisions as well as the impact
      this new legislation is likely to have on healthcare professionals.

PMID- 18073662
TI  - The role and responsibilities of matron: BJN over 100 years ago.

PMID- 18073661
TI  - An audit of nutritional care in a health board in Scotland.
AB  - This article's aim is to describe the processes used and results found when
      conducting an audit of nutritional care within a health board area in Scotland.
      Nutritional standards and an audit tool were developed by a multidisciplinary
      team and all in-patient clinical areas took part. The results demonstrate that
      there is still a considerable amount of work that needs to be undertaken to
      ensure that patients are getting the most effective and efficient nutritional
      care and this article denotes some of the initiatives instilled to address areas
      of identified challenges.

PMID- 18073663
TI  - Assessment is the key!

PMID- 18073664
TI  - Condemned or curious? Don't believe the hype.

PMID- 18073665
TI  - Death by denomination: a Jehovah's right to die.

PMID- 18073666
TI  - The management of venous thromboembolism in cancer patients.
AB  - Venous thromboembolism (VTE), encompassing deep venous thrombosis and pulmonary
      embolism (PE), is a common complication of cancer and an important cause of
      preventable mortality in people with cancer. Because VTE can be clinically
      silent, fatal PE generally occurs without warning, and preventive measures are,
      therefore, necessary in high-risk patients. Clinical guidelines recommend the use
      of low-molecular-weight heparins in the treatment and prevention of VTE in
      patients with cancer, in addition to non-pharmacological interventions aimed at
      reducing thrombotic risk. Nurses have an important role in helping to identify
      patients at risk of developing VTE, and in the implementation of preventive or
      therapeutic regimens, and monitoring the development of complications.
      Furthermore, nurses are in an ideal position to educate patients on the
      importance of preventive measures and to help ensure compliance with
      thromboprophylactic interventions.

PMID- 18073667
TI  - Temperature measurement in children with cancer: an evaluation.
AB  - There is little agreement as to the most appropriate thermometer, the anatomical
      site to carry out temperature measurement in children with cancer, or the type of
      thermometer preferred by the patients. The authors carried out this study to
      assess temperature measurement in children with cancer who were admitted for
      febrile episodes. The body temperatures of children with cancer who were admitted
      consecutively between January and October 2005 to the paediatric department
      because of febrile episodes were measured on admission and over the next 24-36
      hours using an electronic thermometer sublingually as the standard reference
      site. These measurements were compared with those obtained with two ear-based
      thermometers, a forehead thermometer, and from the axilla (representing current
      practice). The parents were asked about the type of thermometer they used at home
      and the children were asked about the type of thermometer they preferred. There
      were 34 admissions during this period, of which 19 (56%) were confirmed as
      febrile. Altogether, 108 sets of temperature measurements were obtained,
      producing a total of 540 measurements from these admissions. Measurements with
      the two ear-based thermometers in febrile children achieved higher sensitivity
      than that with axillary and the forehead measurements. The ear-based thermometer
      was the most common type used at home while the forehead thermometer was the one
      preferred by the children. In conclusion, ear-based temperature measurements in
      febrile children were more accurate than axillary and forehead temperature
      measurements. The current practice of axillary temperature measurement needs to
      be re-considered.

PMID- 18073668
TI  - The safe and responsible disposal of unused controlled drugs.
AB  - There are well-defined legal requirements for the safe storage, handling and
      disposal of controlled drugs (CDs): The Misuse of Drugs Act 1971, and Safer
      Management of Controlled Drugs (Department of Health, 2007). Clinical staff
      involved in the prescription and administration of CDs to patients are
      responsible and accountable for the appropriate disposal of these drugs because
      of the risk of substance abuse. A review of current practice, as followed by
      staff involved in the use and disposal of CDs, has been evaluated in a multi
      centre audit. This audit showed that a wide variation in attitude towards
      disposal of CDs exists among medical and non-medical staff, and that the sample
      hospitals are falling short of meeting proposed standards.

PMID- 18073669
TI  - A comprehensive audit of nursing record keeping practice.
AB  - Good quality record keeping is essential to safe and effective patient care. To
      ensure that high standards of record keeping are maintained, regular clinical
      audit should be undertaken. This article describes an audit and re-audit of
      nursing record keeping at Sheffield Teaching Hospital NHS Foundation Trust. The
      article demonstrates improving audit data in 2005 and 2006 and describes how
      audit and the resulting recommendations and action plans can result in real
      improvements in the quality of record keeping. The keys to success in this
      ongoing audit programme are identified as stakeholder involvement, support from
      the senior nurses in the organization and the use of the data for both local and
      trust-wide purposes.

PMID- 18073670
TI  - The Mental Capacity Act 2005: the new Court of Protection.
AB  - The new Court of Protection is now considered in the series of articles on the
      Mental Capacity Act 2005. The Court of Protection was established on the 1
      October 2007 and has a much wider jurisdiction than its predecessor. It can now
      hear cases concerned with the personal welfare of those who lack the mental
      capacity to make their own decisions, as well as issues relating to property and
      finance which were the sole concern of its predecessor. This article considers
      the powers, procedure, practice, rules and directions of the Court and its power
      to appoint deputies and their role. It also considers the new Office of Public
      Guardian and its role in keeping a register of Deputies and Lasting Powers of
      Attorney. It also considers the appointment of Special and General Visitors. The
      implications of these new institutions are reviewed in the light of a common
      situation involving healthcare practitioners.

PMID- 18073671
TI  - Driving confidence in tomorrow's nurses.

PMID- 18073672
TI  - Pulse oximetry knowledge and its effects on clinical practice.
AB  - AIM: to explore literature pertaining to registered nurses' and/or doctors'
      knowledge in relation to the pulse oximetry in clinical practice. BACKGROUND:
      pulse oximeters provide non-invasive readings of both pulse rate and peripheral
      oxygen saturation, leading to quick identification of potential/actual problems.
      Because of this, clinicians, like nurses, may become too dependent on it,
      neglecting other aspects of the holistic assessment process. METHODS: a
      literature search was carried out between 1980 and 2006, with much of the data
      skewed towards 1994-2006. As the central focus was to be on pulse oximetry
      knowledge of nurses and/or doctors, articles included had to contain a central
      theme addressing this. Other criteria for inclusion were links between pulse
      oximetry and knowledge in clinical practice, nurses and/or doctors as
      participants in studies addressing this, as well as the clinical competency in
      relation to the device. CONCLUSION: improving knowledge may not necessarily be
      the answer in improving clinical competency. Future research will need to be
      carried out to measure the connection between knowledge and competency and to use
      that as a basis for education and training.

PMID- 18073673
TI  - Manners and the administration of fluid into the rectum: BJN 100 years ago.

PMID- 18073674
TI  - Emollients: application of topical treatments to the skin.
AB  - Nurses working in various clinical settings can make a real difference to the
      clinical effectiveness of topical applications to the skin by increasing their
      knowledge of the choice and mechanisms involved. This is particularly the case
      for nurses who are non-medical prescribers when considering first-line therapies
      for patients with eczema. It is important for all nurses to acknowledge that
      topical treatments, however simple, are a form of drug therapy and must be given
      the same considerations for their specific actions whether you are prescribing,
      applying or reviewing their effect. Emollients have an as important part to play
      in the treatment of all dry skin conditions. This article focuses on increasing
      the reader's knowledge of the application of topical emollient therapy, as well
      as highlighting some practical tips to consider.

PMID- 18073675
TI  - Nutritional support for patients with infected wounds.
AB  - Many factors affect wound healing, including nutritional status and recent
      nutritional intake. Patients with infected wounds have increased requirements for
      nutrients and often have a reduced food intake. It is therefore important that
      nutritional status is carefully considered, and all patients should be screened
      for malnutrition using a nutrition screening tool. Nutrition plans should aim to
      provide sufficient energy while maintaining good glycaemic control, adequate
      protein and hydration, and a minimum of 100% reference nutrient intake for
      micronutrients. Measures required to achieve this will vary, as all patients
      should be assessed on an individual basis.

PMID- 18073676
TI  - Exploring inclusion and challenging policy in mainstream education.
AB  - Education is both a human right in itself and an indispensable mean of a better
      future. Removing Barriers to Achievement, published by the Department for
      Education and Skills (DfES, 2004a), highlights its vision for giving children
      with special educational needs and disabilities the opportunity to achieve their
      full potential. Chapter two in particular focuses on removing barriers to
      learning and it is here where the Government focuses, emphasises and justifies
      the issue of inclusion of children with learning difficulties into mainstream
      education (DfES, 2004a). The aim of this article is to explore inclusion and
      simply challenge whether the policy is effective in its purpose by considering
      educational practice today. It is important that nurses from all fields have some
      level of understanding regarding the education of children in the community. This
      is vital to fulfil our role and provide the necessary support to users and
      families of the service.

PMID- 18073677
TI  - Getting us to work together.

PMID- 18073678
TI  - Smoking ban causes less smoke in bars 'shocker'.

PMID- 18073679
TI  - Making a difference with a telehealth service.

PMID- 18073680
TI  - A clinical overview of endometriosis: a misunderstood disease.
AB  - Endometriosis is the presence of endometrial glands and stroma outside the
      endometrial cavity and is the most common known cause of pelvic pain. The number
      of women being diagnosed with the disease is increasing, but this may be
      reflective of improved diagnostic techniques. The aetiology is unknown, although
      the theory of retrograde menstruation remains dominant. Although pain around
      menstruation is the most frequently experienced symptom, dyspareunia, dyschezia,
      cyclical dysuria and extreme fatigue are all common. The 'gold standard'
      diagnostic technique is laparoscopic visualization, and the Royal College of
      Obstetricians and Gynaecologists (2006) recommends that surgical removal of all
      endometriotic lesions is the ideal. The experience of endometriosis can
      negatively affect all aspects of a woman's life and relationships, and this is
      consistently reported in research studies. This article discusses the aetiology
      and clinical aspects of endometriosis as well as giving an overview of empirical
      literature surrounding the experience of the disease. It provides nurses with the
      knowledge to be alert to the possibility of endometriosis as a diagnosis in women
      with a certain set of symptoms, in whatever healthcare setting they work.

PMID- 18073681
TI  - Polycystic ovary syndrome and female reproduction.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women
      of reproductive age. The presentation is diverse. There is no single, unified
      definition of PCOS, no single diagnostic test and no consensus on the diagnostic
      criteria. Currently, PCOS is most commonly defined by the 2003 Rotterdam
      criteria, which requires at least two of three features for diagnosis--chronic
      anovulation, clinical and/or biochemical signs of hyperandrogenism, or polycystic
      ovaries. The aetiology is unknown, but the principal underlying disorder is
      thought to be reduced insulin sensitivity in peripheral tissue, and hence
      hyperinsulinaemia (high levels of insulin in the blood). Some affected women may
      have hyperandrogenism and polycystic ovaries with normal ovulatory function;
      however, like women with classic PCOS, they still have an increased risk of type
      2 diabetes and cardiovascular events. Some women with PCOS have no symptoms or
      signs and live a normal life with normal childbearing status, but it is very
      difficult to predict which cases will follow this pattern. It is important to
      investigate women with menstrual irregularity when they first present, because
      they might have mild PCOS, which could otherwise be missed. It is therefore
      essential to educate the public, nurses and other healthcare professionals to
      identify affected women, so that strategies can be put in place to avoid or
      minimize the complications and consequences of PCOS.

PMID- 18073682
TI  - Change management in cancer care: a one-stop gynaecology clinic.
AB  - 'Creating a Patient-Led NHS' (Department of Health, 2005b) advises us to develop
      services with the patient at the centre of all that we do. In today's current
      agenda for reform and improvement, with the additional pressure on organizations
      to achieve Government performance targets where there is increasing demand and
      limited resources, it is sometimes difficult to provide the optimum patient
      experience. This article describes how a district general hospital used
      continuous quality improvement methodology to improve quality of care when
      developing a one-stop diagnostic clinic for patients urgently referred with
      suspected gynaecological cancer. As well as increasing clinic capacity and
      meeting access targets, redesigning the patient care pathway to improve services
      also provides the opportunity to build in patient choice and convenience. The
      article also discusses how clinical teams can involve patients when planning and
      evaluating services, and explores user involvement as a core component of
      continuous quality improvement methodology.

PMID- 18073683
TI  - Researching the management of constipation in long-term care: Part 1.
AB  - The management of constipation is a problem in any healthcare setting, for a
      variety of reasons. These include the lack of a unified definition of
      constipation, differences in bowel habit between individuals, the lack of
      literature on assessment of constipation and nursing research into the condition,
      and the numerous risk factors. A good knowledge and understanding of these
      factors, which can help not only in dealing with constipation, but also in
      preventing it and maintaining the individual's comfort and health, is essential.
      This two-part article describes a research study carried out in nine care homes,
      among patients of various ages with a variety of chronic conditions. The aim of
      the study was to investigate and improve bowel care in long-term care settings.
      Part 1 presents the background to the study, including the definition, causes,
      risk assessment and management of constipation, which focuses on the role of
      health education and the use of laxatives. The main part of the study and
      implications for practice will be presented in part 2.

PMID- 18073684
TI  - An audit of oxygen therapy on a respiratory ward.
AB  - Oxygen therapy can be a life-saving intervention, which is widely available and
      commonly prescribed by medical staff. Patients often receive oxygen therapy in
      hospital but, like any other drug, oxygen can be dangerous when given in the
      wrong concentration. AIMS: To review the current literature. To examine current
      prescribing practice plus methods of oxygen delivery on a respiratory ward.
      METHOD: A prospective audit was conducted on patients receiving oxygen therapy
      over a 4-week period. The ward was audited pre- and post-education sessions.
      Education was on oxygen prescribing and oxygen therapy. RESULTS: The literature
      revealed that oxygen was often poorly prescribed by doctors and at times poorly
      administered by nurses. Of the 55 patients audited pre-education, only 5% of
      patients had a prescription. This increased to 20% post-education (P=0.042). The
      initial audit uncovered 14 issues surrounding oxygen delivery. This fell to one
      post-education (P<0.001). Reassuringly, all patients had arterial oxygen
      saturation recorded. CONCLUSION: Current rates of oxygen prescribing remain
      unsatisfactory despite doctors being made aware of the audit findings. Education
      on oxygen therapy improved the delivery of oxygen therapy to patients on a
      respiratory ward.

PMID- 18073685
TI  - Mental capacity and decision making: defining capacity.
AB  - The Mental Capacity Act 2005 came fully into force on 1st October 2007 (some
      sections came into force on 1 April 2007). This series of articles considers some
      of the key features of the Act, including the concepts of best interests, the
      lasting power of attorney, the role of the new Court of Protection, the Office of
      Public Guardian and the deputies of the Court, to name but a few. This first
      article looks at the central feature of the Act: how mental capacity is
      determined.

PMID- 18073686
TI  - Using 'cling film' to protect lower limb plaster casts in babies with club foot.
AB  - Clubfoot or congenital talipes equinovarus is a common condition affecting babies
      and non-surgical treatment involves serial manipulation and plaster casting for
      many weeks. The casts are susceptible to soiling during this time, which makes
      management and child care even more challenging. The authors report initial
      experience in a typical district general hospital clubfoot clinic where the
      parents of a baby used conventional cling film to cover the casts and provide a
      low-cost, effective and well-tolerated method of protection. Informal reports
      received from these parents were very positive and encouraging throughout the
      duration of treatment. The authors believe parents with babies undergoing such
      treatment for clubfoot could be advised of the benefits of using cling film to
      protect plaster casts. More formal analysis of feedback from parents and
      collaborative experience with other hospitals is required before widespread use
      is recommended. There may also be scope for using cling film to protect lower
      limb casts used in managing developmental dysplasia of the hip or fractures in
      children and potentially adults.

PMID- 18073687
TI  - Balancing recognition and bureaucracy.

PMID- 18073688
TI  - Erasing the word 'lift' from nurses' vocabulary when handling patients.
AB  - The incidence of back injuries is catastrophic to the nursing profession. It is
      paramount that individual practitioners attempt to significantly reduce the
      number of back injuries in nursing teams. Erasing the word 'lift' from nurses'
      vocabulary when handling patients can empower patients and promote good safe
      practice. This article offers a literature-based discussion of patient handling
      in relation to safety for both patients and nurses. Nurses' handling practice is
      governed by legislation and NHS Trust policies. This article suggests ways of
      developing safe practice that is empowering for both nurses and patients,
      advocating team working and safeguarding the interests of the patient and
      handler.

PMID- 18073689
TI  - The value of curds and whey: BJN over 100 years ago.

PMID- 18073690
TI  - Abuse by care professionals. Part 4: an exploration of available resources.
AB  - This fourth article will explore the resources available to those who are abused
      and also the measures available to prevent abuse by healthcare professionals. It
      was found that, despite good intentions, available measures, which include
      training and supervision of those likely to abuse, changes in environment,
      relying on the victim's own support network and generalist professional support
      networks, are far from adequate. There are a number of measures available to
      prevent abuse by care professionals from happening. These include clinical
      supervision, continuing professional development and training, current research
      awareness and implementation and vastly improved communication between care
      providers. The only organization that appears to be working in the field of abuse
      by healthcare professionals is the London-based voluntary sector organization
      WITNESS.

PMID- 18073691
TI  - Health facilitation in primary care seen from practice and education.
AB  - 'Valuing People: A New Strategy for Learning Disability for the 21st Century'
      (Department of Health, 2001a,b) aimed to introduce 'health facilitation' to
      improve the identification of health needs and access to appropriate care for
      people with learning disabilities. One London Borough took a leading role in
      implementing this new function, in the form of dedicated, full-time health
      facilitators. The authors examined the implementation and its impact, employing
      an innovative collaboration between professionals from practice, education and
      research. The clinical nurse involved was observed during her first year of
      health facilitation. The authors evaluated her impact on professionals, people
      with learning disabilities and the wider system of health. In some areas (for
      example, information technology) the health facilitator could make little
      progress in one year. However, she connected with a widening circle of local
      people and services, for example, in introducing health action plans for adults
      with a learning disability. Across the Borough some professionals became more
      aware of specific health issues in their local population.

PMID- 18073692
TI  - Is health care a right?

PMID- 18073693
TI  - Chronic wound audit: evaluation of a tissue viability service.
AB  - A chronic wound audit was carried out at the Conquest Hospital, East Sussex, to
      establish the prevalence of chronic wounds within the Trust, in light of
      evaluation of the tissue viability service. At the time of audit the Trust
      employed two specialist nurses on a part time basis (3 days a week) with 2 days
      clinical work on the wards. A total of 372 patients were included in the audit,
      56 patients had a total of 82 chronic wounds. These wounds were subdivided into
      wound types. The highest numbers of chronic wounds were pressure ulcers grade 1
      4, including the new category of moisture lesions totalling 47.5%. Surgical
      wounds followed at 20.7%. There was a marked reduction in grade 3-4 pressure
      ulcers consistent with the pressure ulcer prevalence report from August 2006 that
      saw an overall reduction of hospital acquired pressure ulcers of 3.9%. This was
      attributed to the purchase of pressure relieving equipment, the development of a
      pressure ulcer help line and focused education on pressure ulcer prevention
      throughout the wards. The mean bed stay for both medical and surgical patients
      was 28.5 bed days but with surgical patients alone median bed stay was a
      staggering 45.5 days.

PMID- 18073694
TI  - The role of the pathologist in wound management.
AB  - Skin wounds result from a wide variety of physical insults, traumas and
      idiopathic causes. All are prone to infection and vulnerable to dehydration,
      contamination and further damage from environmental insult. Appropriate therapy
      depends upon correct diagnosis of the lesion, wound bed preparation with
      antimicrobial measures as required, and selection and application of suitable
      dressings. Whereas tissue viability clinicians and nurses will routinely assess
      levels of tissue damage and infection through observation of the colour, depth
      and size of wounds, backed up by microbiological assessment, a range of
      laboratory pathological services are available to give a wider picture of
      clinical wounds and possible causes of indolence and non-healing. This review
      identifies the contribution that specialist pathologists can make to identifying
      immunological changes in patients and toxic events resulting from the use of
      xenobiotic materials in wound management, and unravelling the mechanistic action
      of wound care products. Emphasis is placed on the central role of research in
      furthering the study of wound healing and mechanisms of chronicity.

PMID- 18073695
TI  - Don't give me evidence, give me reality!

PMID- 18073696
TI  - Performance indicators--a quest to improve patient care.
AB  - Nurses working in the field of tissue viability constantly strive to improve
      pressure ulcer prevention and management in their clinical areas, knowing that
      pressure ulcers cause pain and suffering to patients while costing the NHS
      millions of pounds to treat. The aim of this initiative was for the tissue
      viability team to develop an audit tool based on recently devised performance
      indicators. The purpose of the audit was to provide the mechanism for reviewing
      the quality of everyday care. The tool utilizes the 'traffic light' system to
      categorize the results. The initiative has improved clinical outcomes for
      patients and increased the awareness, education, knowledge and confidence of
      nurses in pressure ulcer prevention and management across a combined primary and
      secondary care Trust.

PMID- 18073697
TI  - Adherence to a 2-layer compression system for chronic venous ulceration.
AB  - Adherence to compression therapy is fundamental for healing venous leg ulcers
      (Moffatt, 2004). The aim of this study was to investigate adherence and comfort
      associated with using a 2-layer compression system over a 6-week period for the
      management of chronic venous leg ulceration in patients with a history of non
      adherence to other compression systems. Self-report rating scales were completed
      each week by the patients to record adherence and comfort of the compression
      system, while condition and ease of use of the system were recorded each week by
      the nurses involved in their care. The majority of the patients reported wearing
      the compression system for 75% of the time and were considered by the nurses to
      be 'fully adherent' for 80% of the time. Comfort and ease of use were rated
      highly by the majority of patients and nurses respectively.

PMID- 18073698
TI  - Remembrance Day: lest we forget.

PMID- 18073699
TI  - Parental perspectives of initial end-of-life care communication.
AB  - SIGNIFICANCE: an important research priority is to explore parents' perspectives
      of the introduction of end-of-life care (EOL) options for a dying child by their
      health care provider. AIMS: to examine parents' perspectives of: (1) the timing
      and method used by health care providers to introduce EOL options for their child
      and (2) what their preference would have been regarding the selected time and
      method to introduce EOL options. DESIGN: retrospective, descriptive study.
      ANALYSIS: qualitative method, content analysis. RESULTS: the retrospective study
      design gave parents the ability to reflect on what was helpful or harmful when
      health care providers introduce or discuss palliative and end-of-life care
      options for the dying child. Important suggestions were shared regarding when
      this information should be discussed with the parents of a child with a life
      threatening illness.

PMID- 18073700
TI  - Developing a pain and palliative care programme at a US children's hospital.
AB  - Although a number of successful adult combined pain and palliative care
      programmes exist worldwide, integrated paediatric pain and palliative care
      services are rare. This article reviews epidemiology, definition, symptom
      prevalence and myths in paediatric palliative care. It then describes the
      development of the Pediatric Pain and Palliative Care Programme at the Children's
      Hospitals and Clinics of Minnesota, USA. This paediatric service aims to control
      acute, chronic and recurrent pain in all in- and outpatients at the hospitals,
      with follow-up at home. The team also provides holistic, interdisciplinary care
      for children and teens with life-limiting or terminal diseases, and their
      families. It is the only paediatric hospice provider in the state of Minnesota.
      One of the advantages of an integrated Pain and Palliative Care Programme such as
      the one described in this article, may be the provision of care in a continuum
      from acute, chronic or recurrent pain to palliative care and hospice care. This
      example shows, that integrated paediatric pain medicine and palliative care
      programmes can be successfully implemented in a children's hospital setting.

PMID- 18073701
TI  - An audit of the use of the Barthel Index in palliative care.
AB  - The Barthel Index (Mahoney and Barthel, 1965) is an objective tool which assesses
      an individual's ability to perform activities of daily living; for example,
      personal care, mobility, transfers, bathing and feeding. The purpose of this
      study was to investigate whether the Index could be used with patients with life
      threatening illnesses who are admitted to the inpatient intermediate care unit,
      to aid clinical practice, establish patients' current level of function, and
      highlight any progress or deterioration in abilities. The overall aim was to
      facilitate discharge planning and ensure that patients were managed in their
      preferred place of care. This was a clearly defined group of patients in a
      specific clinical area. The authors recognise that to improve consistency of
      findings, the study may need to be applied to a larger cohort of patients with a
      greater research emphasis. The article presents the results of an audit of 50
      patients. The findings suggest that those patients with a low Barthel score on
      admission, or those with a score dropping by ten or more per week, are
      significant predictors of a short prognosis. It concludes that the Barthel Index
      would be a useful tool in the community to prevent inappropriate admission for
      those with a low score where the patient wishes to die at home. It could also be
      used as a monitoring tool to help discharge planning and fast-tracking to the
      preferred place of care in inpatient settings, and may also assist in community
      health care (CHC) planning.

PMID- 18073702
TI  - Watch with me: a chaplain's perspective.
AB  - This article is a reflection of the importance and the difficulty of being
      present to, and with, terminally ill patients within a palliative care setting.
      It is offered as a reflective and interpretive piece on the work of a chaplain
      within the palliative care team. It includes an examination of the way in which
      the death of a patient reminds us of our own mortality and of the often
      unacknowledged terror of death. Questions are asked about the distinctive role of
      the chaplain and what is it that the chaplain and other professionals within the
      palliative care team share. The article is written from a Christian perspective.

PMID- 18073703
TI  - Introducing guided group reflective practice in an Irish palliative care unit.
AB  - This paper describes the processes involved over one year in introducing,
      facilitating and evaluating a project of guided reflective practice for a group
      of eight palliative care nurses in Milford Care Centre, Republic of Ireland.
      While literature has tended to concentrate on critical discussion relating to
      reflection, less attention has been directed towards the organisation and
      facilitation of reflective processes in practice. In addressing this deficit, a
      detailed account of the collaborative processes and challenges involved in this
      project are presented. Group evaluation of the project is discussed under the
      following themes: understanding the process of reflective practice; the value of
      keeping a reflective diary; guided group reflection and moving forward. The
      introduction of guided reflection for palliative care nurses has afforded both
      the facilitators and the participants an opportunity to meet away from the
      clinical environment, and to work together, finding fresh insights to inform
      practice. The valuing and promotion of reflective processes by an organisation
      arguably provides a fundamental strategy to support nurses in a quality
      palliative care setting.

PMID- 18073705
TI  - Intercultural palliative care: do we need cultural competence?
AB  - Recognition of the importance of 'cultural competence' is now central to health
      care policy and to nurse education and training across the international
      spectrum. Detailed engagement with models of cultural competence is comparatively
      recent in palliative care nursing. This article presents the findings from a
      development project on elders and carers from 'minority ethnic' groups, funded by
      the Department of Health, to increase awareness of palliative care and to improve
      understanding of the needs of these groups of service users. The article
      describes the experiences of nurses involved in the delivery of palliative care
      who were interviewed in focus groups as a part of the project. It draws attention
      to the complicated relationships between cultural knowledge and practice and to
      the non-rational and visceral dimensions of intercultural care. These aspects of
      nursing are marginalised in current approaches to cultural competence, which
      emphasise the rational acquisition and application of cultural knowledge and
      skills by practitioners. It is suggested that recognition of these marginalised
      experiences can contribute to the development of new approaches to intercultural
      nursing that are also more attuned to the ethos and values of palliative care.

PMID- 18073706
TI  - Children's needs when facing the death of a parent from cancer: part one.
AB  - A small exploratory study was conducted to identify the psychosocial needs of
      children facing the death and subsequent bereavement of a parent from cancer. The
      focus was on the palliative phase of care through the bereavement period with the
      aim of identifying the best way forward in further developing a community-based
      service for children in Fife. This paper selectively reviews the literature
      related to children's and families' needs when facing and dealing with the death
      of a parent, bringing into focus some of the work available to inform thinking
      and planning in this area. It then describes the methods used to conduct this
      exploratory study and reports the issues which will be considered as a basis for
      future service development.

PMID- 18073707
TI  - Treatment options in end-of-life care: the role of palliative chemotherapy.
AB  - Advances in medical science and technology, combined with the primary goal of
      medical care to restore or maintain health as far as possible, often result in
      the transition from active to palliative care being blurred. Treatment choices
      are limited in advanced disease; but paradoxically, which therapy to choose is
      becoming an increasingly complex decision (Weissman, 2004). The role of
      chemotherapy in this phase remains a controversial subject, but data are emerging
      to show that an increasing number of patients nearing the end of life are
      receiving chemotherapy (Matsuyama et al, 2006), and there is a mounting body of
      evidence for its use in symptom palliation (Cullen, 2003; Bowcock et al, 2004;
      Davis, 2005). Therefore, the traditional view that medical oncology and
      palliative care are two distinct disciplines may need to be modified.

PMID- 18073708
TI  - Thinking about nursing practice and culture: syringe drivers.
AB  - We recently set up a new inpatient unit and this involved making various
      decisions about our philosophy and approach to nursing practice (Shaw et al,
      2007). One of the clinical issues we had to deal with was how to manage syringe
      drivers. Syringe drivers had been used within the community for many years, and
      local guidelines about their use along with various policies and procedures
      existed. We considered all of this information and asked some critical questions
      about it. One of the most practical issues we explored was the volume (or length)
      of infusions. This single issue and our response to it caused a significant
      amount of reaction among colleagues. We have written this article in an attempt
      to explain some of the issues relating to nursing practice and culture as we
      perceive them and to raise questions about why and how professionals sometimes
      respond to changes in practice.

PMID- 18073709
TI  - Sleep disturbance in family caregivers of patients with advanced cancer.
AB  - Sleep is a complex process known to be essential for health, well-being, and
      optimal physical and psychological functioning. Therefore, sleep disturbance may
      lead to serious consequences. Advanced cancer patients are known to experience a
      complex constellation of symptoms requiring round-the-clock care. This reality,
      coupled with the current demographic, social, economic and health policy trends
      which are shifting palliative care from the hospital to the community setting,
      will see family members increasingly assuming responsibility for the provision of
      this care at home. Despite the positive aspects of caregiving, studies report
      that families experience stress and exhaustion. Given that patient and family
      constitute the unit of care in palliative care, this area warrants our attention.
      This article reviews the literature related to family caregivers' disturbed sleep
      while caring for someone with advanced cancer. What is known and directions for
      future research will be addressed.

PMID- 18073710
TI  - Interprofessional working: communication, collaboration... perspiration!
AB  - Palliative care is rarely delivered by one provider; for most patients their care
      will be managed by community and one or more hospital teams at the least. This
      can be problematic for patients, their family and friends, and health
      professionals. Evidence suggests that, in general, providers work in isolation
      from each other. Although formal processes are in place for transfer of
      information between the sectors on discharge between acute and community sectors,
      there is a de facto lack of communication and therefore a lack of appreciation of
      the working practices within each environment. This resulting lack of
      collaboration between teams can lead to disruptive care that detracts from the
      holistic philosophy purported to be the basis of supportive and palliative care
      (National Institute for Health and Clinical Excellence (NICE) 2004; Department of
      Health (DH) 2000). In October 2005, 20% of a clinical nurse specialist's (CNS)
      full-time post was dedicated to working between the palliative care teams of
      Central Manchester and Manchester Children's NHS Trust (CMMC) and Central
      Manchester PCT (CMPCT). The aim was to improve communication and dialogue to
      promote more effective integrated working between the two sites and develop
      effective interprofessional working. This article will evaluate the impact of
      this new post, after 18 months, on collaboration between the teams, their
      practices and their patients. Finally, it will offer recommendations for future
      development.

PMID- 18073711
TI  - Hospice: the heart of end-of-life-care.

PMID- 18073712
TI  - Can a pulsatile left ventricular assist device provide destination therapy for
      patients with severe heart failure?

PMID- 18073714
TI  - The total artificial heart in refractory cardiogenic shock: saving the patient
      versus saving the heart.

PMID- 18073713
TI  - The role of salt in hypertension: the complexity seems to become clearer.

PMID- 18073715
TI  - Does genetic screening increase detection of familial medullary thyroid cancer in
      apparently sporadic cases?

PMID- 18073716
TI  - Does treatment with 17 alpha-hydroxyprogesterone caproate increase the risk of
      gestational diabetes mellitus?

PMID- 18073717
TI  - How effective is natalizumab induction therapy in patients with Crohn's disease?

PMID- 18073718
TI  - Is the inhibitory control test as accurate as standard psychometric testing for
      diagnosing hepatic encephalopathy?

PMID- 18073719
TI  - How useful is combined chromoendoscopy and endomicroscopy in patients with
      ulcerative colitis?

PMID- 18073720
TI  - Are children with lesser-risk B-lineage acute lymphoblastic leukemia curable with
      antimetabolite therapy?

PMID- 18073721
TI  - Are women with breast cancer receiving sufficient education and information about
      their treatment?

PMID- 18073722
TI  - Subclinical renal allograft rejection and protocol biopsies: quo vadis?

PMID- 18073723
TI  - How can the safety and diagnostic yield of percutaneous renal biopsies be
      optimized?

PMID- 18073724
TI  - Does patient age affect the stone-free rate in patients with urinary calculi
      treated with extracorporeal SWL?

PMID- 18073725
TI  - Is high-dose chemotherapy effective in patients with relapsed or refractory germ
      cell tumors?

PMID- 18073726
TI  - Cytokines and joint erosion in arthritis.

PMID- 18073727
TI  - The importance of the heart in cluster headache treatment.

PMID- 18073728
TI  - Which MRI sequences are best suited to the evaluation of patients with
      neurocysticercosis?

PMID- 18073770
TI  - Argonaute proteins: key players in RNA silencing.
AB  - During the past decade, small non-coding RNAs have rapidly emerged as important
      contributors to gene regulation. To carry out their biological functions, these
      small RNAs require a unique class of proteins called Argonautes. The discovery
      and our comprehension of this highly conserved protein family is closely linked
      to the study of RNA-based gene silencing mechanisms. With their functional
      domains, Argonaute proteins can bind small non-coding RNAs and control protein
      synthesis, affect messenger RNA stability and even participate in the production
      of a new class of small RNAs, Piwi-interacting RNAs.

PMID- 18073771
TI  - Apoptosis: controlled demolition at the cellular level.
AB  - Apoptosis is characterized by a series of dramatic perturbations to the cellular
      architecture that contribute not only to cell death, but also prepare cells for
      removal by phagocytes and prevent unwanted immune responses. Much of what happens
      during the demolition phase of apoptosis is orchestrated by members of the
      caspase family of cysteine proteases. These proteases target several hundred
      proteins for restricted proteolysis in a controlled manner that minimizes damage
      and disruption to neighbouring cells and avoids the release of immunostimulatory
      molecules.

PMID- 18073772
TI  - Spared caudal brainstem SERT binding in early Parkinson's disease.
AB  - Postmortem data indicate loss of serotoninergic neurons in Parkinson's disease
      (PD). We used the serotonin transporter (SERT) radioligand 3-amino-4-(2
      dimethylaminomethyl-phenylsulfaryl)-benzonitril (DASB) and positron emission
      tomography to examine SERT distribution and changes in early PD subjects. We
      studied five PD subjects (H&Y 1 to 2.5) and eight normal controls. There is
      reduced SERT binding in PD. The magnitude of DASB binding reductions was greater
      in the forebrain than in the brainstem regions. There was no asymmetry of
      diminished SERT binding. DASB binding in the medulla was relatively spared,
      inconsistent with the description of early prominent pathologic study in these
      caudal brainstem nuclei.

PMID- 18073773
TI  - Mechanistic role of calpains in postischemic neurodegeneration.
AB  - The calpain family of proteases is causally linked to postischemic
      neurodegeneration. However, the precise mechanisms by which calpains contribute
      to postischemic neuronal death have not been fully elucidated. This review
      outlines the key features of the calpain system, and the evidence for its causal
      role in postischemic neuronal pathology. Furthermore, the consequences of
      specific calpain substrate cleavage at various subcellular locations are
      explored. Calpain substrates within synapses, plasma membrane, endoplasmic
      reticulum, lysosomes, mitochondria, and the nucleus, as well as the overall
      effect of postischemic calpain activity on calcium regulation and cell death
      signaling are considered. Finally, potential pathways for calpain-mediated
      neurodegeneration are outlined in an effort to guide future studies aimed at
      understanding the downstream pathology of postischemic calpain activity and
      identifying optimal therapeutic strategies.

PMID- 18073774
TI  - A modified mini-stroke model with region-directed reperfusion in rat cortex.
AB  - Mini-ischemia localized into a specific brain area has promoted understanding of
      the mechanisms underlying brain recovery in stroke. However, the conventional
      mini-stroke model adopted permanent arterial ligations but lacked controllable
      reperfusion, which is crucial for the outcome of delayed functional recovery. In
      this study, we devised a new rat mini-stroke model in which the vascular
      ligations can be easily reversed to induce targeted reperfusion. Specifically, a
      flexible ring was incorporated into the conventional small arterial ligations to
      tighten the ligating loops and facilitate cutting the ligatures for sufficient
      reperfusion afterwards. The distribution of cerebral blood flow was explored
      directly through a cranial window using laser speckle contrast imaging. A
      distinct ischemic core, which well fits the profile of the ligated ring, was
      bordered by a penumbral zone and then together surrounded by nonischemic tissue
      immediately after the arterial ligations involving the ring. After cutting the
      ligatures, post-recanalization hyperperfusion occurred in the previous ischemic
      core and to a greater extent at 24 h after reperfusion. In contrast,
      recirculation of common carotid artery in the conventional mini-stroke model
      hardly altered hypoperfusion status within the ischemic core. Evidence from two
      kinds of control groups indicated that the ring might produce a compression
      effect on the underlying cortex and then contribute to the more highly localized
      infarct that was identified by triphenyltetrazolium chloride staining. Our data
      suggest that this model provides opportunities for investigating the
      neurovascular dynamics in acute stroke and rehabilitation, especially with
      emerging optical imaging techniques.

PMID- 18073776
TI  - The expectant brain: adapting for motherhood.
AB  - A successful pregnancy requires multiple adaptations of the mother's physiology
      to optimize fetal growth and development, to protect the fetus from adverse
      programming, to provide impetus for timely parturition and to ensure that
      adequate maternal care is provided after parturition. Many of these adaptations
      are organized by the mother's brain, predominantly through changes in
      neuroendocrine systems, and these changes are primarily driven by the hormones of
      pregnancy. By contrast, adaptations in the mother's brain during lactation are
      maintained by external stimuli from the young. The changes in pregnancy are not
      necessarily innocuous: they may predispose the mother to post-partum mood
      disorders.

PMID- 18073775
TI  - From inflammation to sickness and depression: when the immune system subjugates
      the brain.
AB  - In response to a peripheral infection, innate immune cells produce pro
      inflammatory cytokines that act on the brain to cause sickness behaviour. When
      activation of the peripheral immune system continues unabated, such as during
      systemic infections, cancer or autoimmune diseases, the ensuing immune signalling
      to the brain can lead to an exacerbation of sickness and the development of
      symptoms of depression in vulnerable individuals. These phenomena might account
      for the increased prevalence of clinical depression in physically ill people.
      Inflammation is therefore an important biological event that might increase the
      risk of major depressive episodes, much like the more traditional psychosocial
      factors.

PMID- 18073777
TI  - Drug safety in pregnant women and their babies: ignorance not bliss.
AB  - Although clinical trials address questions regarding drug safety for most
      segments of the population, pregnant women constitute one special group that is
      "orphaned" with respect to this issue. The lack of adequate pregnancy safety
      information for the vast majority of medications, combined with a need to make
      appropriate treatment decisions and to communicate risk information to a
      potentially vulnerable population, are some of the most challenging and critical
      women's health issues.

PMID- 18073778
TI  - Cathepsin K inhibitors: a novel target for osteoporosis therapy.
AB  - Osteoporosis is characterized by low bone mass with skeletal fragility and an
      increased risk of fracture. This bone loss is brought about by an imbalance
      between bone resorption and formation. Cathepsin K is the most abundant cysteine
      protease expressed in the osteoclast and is believed to be instrumental in bone
      matrix degradation necessary for bone resorption. Cathepsin K inhibitors
      represent a novel target for developing agents to treat osteoporosis and other
      disorders characterized by increased bone resorption.

PMID- 18073779
TI  - Baseline plasma plant sterol concentrations do not predict changes in serum
      lipids, C-reactive protein (CRP) and plasma plant sterols following intake of a
      plant sterol-enriched food.
AB  - BACKGROUND/OBJECTIVES: Plant sterol (PS) consumption lowers serum cholesterol
      levels, while modestly increasing plasma PS concentrations. Plasma PS
      concentrations may reflect sterol absorption, thus individuals with high plasma
      plant sterol (HPS) concentrations may show greater changes in circulating
      cholesterol and PS than individuals with low plasma plant sterol (LPS)
      concentrations. The objective of this study was to examine whether HPS and LPS
      concentrations are related to subsequent changes in plasma PS, serum lipid and C
      reactive protein (CRP) concentrations, following dietary PS intake in otherwise
      healthy hypercholesterolemic men. SUBJECTS/METHODS: This single-blinded,
      randomized, diet-controlled study consisted of two 4-week phases, separated by a
      4-week washout, where a diet with a placebo or the 2.0 g per day PS-enriched
      spread was consumed during the phases. RESULTS: At baseline, men with HPS
      possessed higher (P<0.01) mean serum cholesterol concentration, while those with
      LPS had higher (P<0.05) body mass index. Following PS intake, plasma sum of
      campesterol plus sitosterol concentrations were elevated from 34.6+/-4.2 to
      46.2+/-3.3 micromol l(-1) (mean+/-SE) and 16.5+/-0.9 to 20.8+/-1.2 micromol l(-1)
      after PS intake in men with HPS and LPS, respectively. Changes in plasma PS
      concentrations, however, were not different between individuals with either HPS
      or LPS baseline concentrations. Total cholesterol and low-density lipoprotein
      cholesterol levels were decreased (P<0.0001) by 6.3 and 7.8%, respectively, with
      PS consumption for all individuals. Changes in lipid parameters were not
      different between individuals with HPS or LPS baseline concentrations. No changes
      in CRP were apparent subsequent to PS intervention. CONCLUSIONS: Baseline plasma
      PS concentrations are not associated or predictive of changes in serum
      cholesterol or plasma PS concentrations after PS intervention. Thus, individuals
      with HPS show similar increases in PS concentrations as individuals with LPS
      following PS supplementation. Plasma PS remained in the range of previously
      reported concentrations.

PMID- 18073780
TI  - Seasonal variations in the relationship between mid-upper arm circumference and
      maximum voluntary contraction among Ethiopian farmers.
AB  - OBJECTIVES: To determine the nature of the relationship between mid-upper arm
      circumference (MUAC) and maximum voluntary contraction (MVC) in pre- and post
      harvest seasons among adult Ethiopian farmers. SUBJECTS/METHODS: A total of 491
      healthy adult men aged 18-60 years were recruited at pre-harvest season and
      followed up at post-harvest season. Anthropometric measurements (weight, MUAC,
      biceps/triceps skinfold thickness and forearm circumference) were obtained using
      standard techniques and arm muscle circumference (AMC)/arm muscle area (AMA) was
      calculated. MVC of both arms was measured using a handgrip dynamometer. Paired t
      test was used to compare means, and linear regression to investigate the
      relationship between MUAC and MVC. RESULTS: Maximum voluntary contraction showed
      statistically significant correlation with MUAC. Grip strength (MVC) demonstrated
      a linear increase from under-nourished to normal subjects across MUAC classes.
      Paradoxically, mean MVC of both arms declined significantly during the post
      harvest season. However, the relationship between MUAC and MVC held tight in the
      post-harvest season as seen in the pre-harvest period. CONCLUSIONS: This study
      has highlighted that under-nourished adult men have reduced functional ability
      (strength) in all seasons. In addition, strength increases in a linear fashion as
      MUAC increases during both seasons. More work examining the relationship between
      functional ability and anthropometric indices in adults from different developing
      countries is needed to address use and cutoffs for grip strength.

PMID- 18073781
TI  - Genetic structure of the invasive pest Bemisia tabaci: evidence of limited but
      persistent genetic differentiation in glasshouse populations.
AB  - The geographic range of plant pests can be modified by the use of glasshouses.
      Bemisia tabaci, originating from warm to hot climates, has been shown to be a
      complex of distinct genetic groups with very limited gene flow. The genetic
      structure of this pest was studied in glasshouses in southern France, a region
      beyond the northern limit of its open-field development area in Europe. Seven
      microsatellite loci were scored in 22 populations sampled from various regions
      over 3 years. Two genetic groups were distinguished using a Bayesian clustering
      method and were assigned to the so-called biotypes B and Q using the gene
      sequence of cytochrome oxidase 1 (CO1). All but one population corresponded to
      biotype Q, even though only biotype B was previously reported. Despite the
      enclosed environment of glasshouses and their expected isolation due to low
      outdoor survival during the winter, only limited differentiation among biotype Q
      glasshouses was observed. A single sample site was notable for a decrease in
      expected heterozygosity and the mean number of alleles over the years. The lack
      of spatial genetic structure among biotype Q populations was indicative of a
      recent colonization event combined with large dispersal at all spatial scales.
      This migration pattern of biotype Q populations was further supported by
      additional CO1 sequences, since individuals from France, Asia and America
      exhibited 100% nucleotide identity. The evolution of genetic diversity observed
      in glasshouses in France is part of the worldwide invasion of biotype Q, which is
      discussed in light of human activities.

PMID- 18073782
TI  - Hakuna Nematoda: genetic and phenotypic diversity in African isolates of
      Caenorhabditis elegans and C. briggsae.
AB  - Caenorhabditis elegans and C. briggsae have many parallels in terms of
      morphology, life history and breeding system. Both species also share similar low
      levels of molecular diversity, although the global sampling of natural
      populations has been limited and geographically biased. In this study, we
      describe the first cultured isolates of C. elegans and C. briggsae from sub
      Saharan Africa. We characterize these samples for patterns of nucleotide
      polymorphism and vulva precursor cell lineage, and conduct a series of hybrid
      crosses in C. briggsae to test for genetic incompatibilities. The distribution of
      genetic diversity confirms a lack of geographic structure to C. elegans sequences
      but shows genetic differentiation of C. briggsae into three distinct clades that
      may correspond to three latitudinal ranges. Despite low levels of molecular
      diversity, we find considerable variation in cell division frequency in African
      C. elegans for the P3.p vulva precursor cell, and in African C. briggsae for
      P4.p, a variation that was not previously observed in this species. Hybrid
      crosses did not reveal major incompatibilities between C. briggsae strains from
      Africa and elsewhere, and there was some evidence of inbreeding depression. These
      new African isolates suggest that important ecological factors may be shaping the
      patterns of diversity in C. briggsae, and that despite many similarities between
      C. elegans and C. briggsae, there may be more subtle differences in their natural
      histories than previously appreciated.

PMID- 18073783
TI  - The spread of a beneficial mutation in experimental bacterial populations: the
      influence of the environment and genotype on the fixation of rpoS mutations.
AB  - The spread of beneficial mutations through populations is at the core of
      evolutionary change. A long-standing hindrance to understanding mutational sweeps
      was that beneficial mutations have been slow to be identified, even in commonly
      studied experimental populations. The lack of information on what constitutes a
      beneficial mutation has led to many uncertainties about the frequency, fitness
      benefit and fixation of beneficial mutations. A more complete picture is
      currently emerging for a limited set of identified mutations in bacterial
      populations. In turn, this will allow quantitation of several features of
      mutational sweeps. Most importantly, the 'benefit' of beneficial mutations can
      now be explained in terms of physiological function and how variations in the
      environment change the selectability of mutations. Here, the sweep of rpoS
      mutations in Escherichia coli, in both experimental and natural populations, is
      described in detail. These studies reveal the subtleties of physiology and
      regulation that strongly influence the benefit of a mutation and explain
      differences in sweeps between strains and between various environments.

PMID- 18073784
TI  - Using principle component analysis to compare genetic diversity across polyploidy
      levels within plant complexes: an example from British Restharrows (Ononis
      spinosa and Ononis repens).
AB  - The investigation of genetic diversity between related plant populations which
      differ in ploidy levels is problematic, with common statistical methods developed
      for diploids being inappropriate for polyploid species. Studies into gene flow in
      such complexes are critical and can shed light on the mechanisms that generate
      and maintain populations of different polyploidy levels. We have investigated the
      use of principle component (PCO) analysis as one approach to elucidate population
      structure within British Restharrows (Leguminsoae, Ononis spp). Restharrows were
      common agricultural weed species until the advent of mechanical ploughing and
      both diploid (2n=2x=30; O. spinosa and O. intermedia) and tetraploid (2n=4x=60;
      O. repens and O. maritima) taxa exist. Patterns of genetic diversity were
      investigated among British Restharrows using 10 microsatellite loci with 21
      Restharrow populations analysed (411 individual plants) from Central and Eastern
      Britain. PCO analysis revealed clear genetic differentiation of the sampled
      plants into two groups, corresponding to O. spinosa/O. intermedia (diploid) and
      O. repens/O. maritima (tetraploid) plants. Evidence of genetic differentiation by
      distance was also revealed for O. repens/O. maritima, but not for O. spinosa/O.
      intermedia. The data suggest the presence of strong reproductive barriers between
      diploid and tetraploid Restharrows in Britain, but not within ploidy levels. This
      genetic isolation between ploidy levels is confirmed by a detailed analysis of a
      sympatric site (Harton Down Hill). These results demonstrate that PCA analysis is
      a suitable general tool for comparing related species of different ploidy levels.

PMID- 18073787
TI  - Digital speckle-pattern interferometry as a full-field fluid-velocimetry
      technique.
AB  - We present a novel fluid-velocimetry technique based on speckle interferometry.
      The light scattered from an illuminated plane is recorded with a CCD camera at
      the same time as a speckled reference beam. Substraction of two nonsimultaneous
      frames provides information about the velocity field for an out-of-plane
      component. An application to a Rayleigh-Benard convective flow is given.

PMID- 18073788
TI  - Excitable wave patterns in a spatially extended nonlinear optical cavity.
AB  - We show that finite external excitation can lead to a traveling wave in an
      excitable passive optical system with one-dimensional space geometry. We have
      studied the excitable behavior of this system in parallel with that of its
      diffusive counterpart and show the effects of optical phase on the traveling-wave
      solution and its velocity. In two-dimensional space we observe numerically
      rotating optical spiral waves evolving from a truncated planar wave front.

PMID- 18073786
TI  - Biologically based modeling of multimedia, multipathway, multiroute population
      exposures to arsenic.
AB  - This article presents an integrated, biologically based, source-to-dose
      assessment framework for modeling multimedia/multipathway/multiroute exposures to
      arsenic. Case studies demonstrating this framework are presented for three US
      counties (Hunderton County, NJ; Pima County, AZ; and Franklin County, OH),
      representing substantially different conditions of exposure. The approach taken
      utilizes the Modeling ENvironment for TOtal Risk studies (MENTOR) in an
      implementation that incorporates and extends the approach pioneered by Stochastic
      Human Exposure and Dose Simulation (SHEDS), in conjunction with a number of
      available databases, including NATA, NHEXAS, CSFII, and CHAD, and extends
      modeling techniques that have been developed in recent years. Model results
      indicate that, in most cases, the food intake pathway is the dominant contributor
      to total exposure and dose to arsenic. Model predictions are evaluated
      qualitatively by comparing distributions of predicted total arsenic amounts in
      urine with those derived using biomarker measurements from the NHEXAS--Region V
      study: the population distributions of urinary total arsenic levels calculated
      through MENTOR and from the NHEXAS measurements are in general qualitative
      agreement. Observed differences are due to various factors, such as
      interindividual variation in arsenic metabolism in humans, that are not fully
      accounted for in the current model implementation but can be incorporated in the
      future, in the open framework of MENTOR. The present study demonstrates that
      integrated source-to-dose modeling for arsenic can not only provide estimates of
      the relative contributions of multipathway exposure routes to the total exposure
      estimates, but can also estimate internal target tissue doses for speciated
      organic and inorganic arsenic, which can eventually be used to improve evaluation
      of health risks associated with exposures to arsenic from multiple sources,
      routes, and pathways.

PMID- 18073789
TI  - A single molecule as a probe of optical intensity distribution.
AB  - Single terrylene molecules embedded in microscopic p-terphenyl crystals are
      identified with the technique of fluorescence excitation spectroscopy. By use of
      the architecture of a scanning-probe microscope at T = 1.4 K , a single molecule
      is scanned through an excitation laser beam while the fluorescence signal is
      recorded. In this manner we have mapped the intensity distribution in a one
      dimensional optical standing wave, demonstrating the potential of a single
      molecule as a nanometric probe. We discuss future experiments aimed at combining
      the high spatial and spectral sensitivity of a single molecule.

PMID- 18073790
TI  - Measuring Stokes parameters by means of a polarization grating.
AB  - Ordinary gratings act on the amplitude and (or) the phase of a wave front.
      Polarization gratings produce instead a periodic modulation of the state of
      polarization. A simple grating of the latter type is constituted by a linear
      polarizer whose orientation varies periodically along a line. It is shown that,
      for a generic polarization state of the incident field, such a grating gives rise
      to first-order diffracted beams with counterrotating circular polarizations. It
      is also shown that such a grating can be used for measuring the Stokes parameters
      of a light beam in an achromatic manner. Several extensions are briefly
      discussed.

PMID- 18073791
TI  - Deflection and diffraction of x rays bound to curved surfaces.
AB  - We present two new x-ray optical effects observed on a whispering-gallery
      waveguide. The first is a gradual in-surface deflection of guided waves caused by
      the non-Euclidean intrinsic curvature of the waveguide surface. The second is the
      excitation of in-surface dynamical diffraction modes that reflects the strong
      influence of the surface photonic band structure of a crystalline waveguide. Both
      phenomena portend a rich array of basic and applied x-ray optical potentialities.

PMID- 18073792
TI  - Ultraviolet filtered Rayleigh scattering temperature measurements with a mercury
      filter.
AB  - We report the development of ultraviolet filtered Rayleigh scattering as a
      diagnostic tool for measurements of gas properties. A frequency-tripled narrow
      linewidth Ti:sapphire laser illuminates a sample, and Rayleigh scattered light is
      imaged through a mercury-vapor absorption filter. Working in the ultraviolet
      improves the signal-to-noise ratio compared with that previously obtained in the
      visible as the result of an enhanced scattering cross section as well as the
      nearly ideal properties of the mercury filter. Tuning the laser through the
      absorption notch of the filter is a means of probing the scattering line shape,
      which contains temperature information. Temperature measurements of air are shown
      to have uncertainties of less than 3%.

PMID- 18073793
TI  - Multiwave coupling in a high-gain photorefractive polymer.
AB  - The characteristics of a new high-gain photorefractive polymer composite with a
      PNP chromophore are investigated. Competition between beam fanning and two-wave
      coupling (TWC) is predicted and verified experimentally. The intensity dependence
      of TWC gain is studied. Higher diffraction order and forward phase conjugation in
      a TWC geometry are observed and explained.

PMID- 18073794
TI  - Optical fiber nanometer-scale Fabry-Perot interferometer formed by the ionic self
      assembly monolayer process.
AB  - The ionic self-assembly monolayer process is a novel technique that has already
      been used to deposit ultrathin films on glass, polymer, and silicon substrates of
      different sizes and shapes. This technique is presented as a new tool with which
      to apply coatings on optical fibers. A nanometer-scale interferometric cavity was
      built up at the end of an optical fiber with discrete thickness increments of
      4.75 nm for a total thickness of 1 mum . Theoretical and experimental aspects of
      the nanometer-scale Fabry-Perot cavity are described, and both theoretical and
      experimental results show good agreement.

PMID- 18073795
TI  - Fiber-optic extrinsic Fabry-Perot interferometer sensors with three-wavelength
      digital phase demodulation.
AB  - A three-wavelength-based passive quadrature digital phase-demodulation scheme has
      been developed for readout of fiber-optic extrinsic Fabry-Perot interferometer
      vibration, acoustic, and strain sensors. This scheme uses a superluminescent
      diode light source with interference filters in front of the photodiodes and real
      time arctan calculation. Quasi-static strain and dynamic vibration sensing with
      up to an 80-kHz sampling rate is demonstrated. Periodic nonlinearities owing to
      dephasing with increasing fringe number are corrected for with a suitable
      algorithm, resulting in significant improvement of the linearity of the sensor
      characteristics.

PMID- 18073796
TI  - Fabrication of high-spatial-frequency gratings through computer-generated near
      field holography.
AB  - We demonstrate an innovative method for fabrication of high-spatial-frequency
      grating structures. This technique makes use of the near-field diffraction
      patterns from computer-generated phase holograms for lithographic fabrication of
      grating structures with periods that are one half that of the phase hologram
      mask. Linear, rectilinear, and circular gratings were fabricated with this
      technique. Experimental results from gratings with periods to 0.5 mum and feature
      sizes to ~0.2 mum are presented.

PMID- 18073797
TI  - Pupil-plane filtering for improved signal detection in an optical data-storage
      system incorporating a solid immersion lens.
AB  - A pupil-plane filtering technique is applied to data-signal detection in an
      optical data-storage system that uses a solid immersion lens (SIL) and a four
      layered phase-change recording medium. We have confirmed by numerical
      calculations and experiment that the technique improves signal contrast and makes
      the contrast less sensitive to the gap width between the bottom surface of the
      SIL and the top surface of the recording medium. Light that is incident upon the
      objective lens that is used with the SIL is linearly polarized, and the full
      vectorial feature of the light is considered in the calculations.

PMID- 18073798
TI  - Optical particle trapping with computer-generated holograms written on a liquid
      crystal display.
AB  - Computer-generated holograms written on a liquid-crystal display can be used to
      generate dynamic light fields of arbitrary shape. This method was used to
      simultaneously trap polystyrene particles laterally and to displace them
      independently of one another.

PMID- 18073799
TI  - Pupil-plane speckle imaging with a referenced polarization technique.
AB  - Pupil-plane speckle imaging is demonstrated by use of a polarimeter to estimate
      the complex wave front from an actively illuminated target. An experimental
      technique, referenced polarization imaging (RPI), closely parallels optical
      heterodyne imaging but is easier to perform in a laboratory. Further, RPI is less
      sensitive to target motions than the heterodyne method. The RPI technique is
      described, along with experimental results.

PMID- 18073800
TI  - Stable and widely tunable all-fiber Pr(3+)-doped cw laser system using fiber
      Bragg gratings.
AB  - A simple and strictly all-fiber 1300-nm cw laser is presented. It is tunable over
      16 nm with 0.5-nm linewidth and several milliwatts of output power in the whole
      tuning range from 1292 to 1308 nm. The setup uses a fiber Bragg grating as a
      combined tuning element and narrow-band output mirror. The simplicity and
      stability of this system are due to the following two characteristics: First,
      polarization control is not necessary anywhere in the system, and second, a
      wavelength-selective system and a narrow-band mirror are combined into one novel
      fiber-optic element.

PMID- 18073801
TI  - Stability of an Er-Yb-doped fiber distributed-feedback laser with external
      reflections.
AB  - The maximum tolerable amplitude backreflection coefficient r(ext,c) into a fiber
      distributed-feedback laser before the onset of instability has been investigated.
      r(ext,c) was found to decrease with increasing external cavity lengths up to ~320
      m and to be proportional to the relative linewidth of the relaxation oscillation
      resonance. The tolerable length of Rayleigh backscattering standard telecom fiber
      was found to be 135-200 m. An observed degradation in the laser stability and
      slope efficiency at low pump powers is believed to be due to UV-induced saturable
      absorbers.

PMID- 18073802
TI  - Diffraction-limited laser beam shaping by use of computer-generated holograms
      with dislocations.
AB  - A new method that reshapes a Gaussian laser beam into a polygon of diffraction
      limited size with a flat or a pyramidal top is presented. The technique is based
      on the use of computer-generated holograms with phase dislocations
      (singularities).

PMID- 18073803
TI  - Differential phase contrast in optical coherence tomography.
AB  - We report on a modification of optical coherence tomography (OCT) that allows one
      to measure small phase differences between beams traversing adjacent areas of a
      specimen. The sample beam of a polarization-sensitive low-coherence
      interferometer is split by a Wollaston prism into two components that traverse
      the object along closely spaced paths. After reflection at the various sample
      surfaces, the beams are recombined at the Wollaston prism. Any phase difference
      encountered between the two beams is converted into a change of polarization
      state of the recombined beam. This change is measured, and the resulting signals
      are converted to differential phase-contrast OCT images. The first images
      obtained from simple test objects allowed us to determine path-difference
      gradients with a resolution of the order of 5 x 10(-5) .

PMID- 18073804
TI  - Efficient gas-phase generation of coherent vacuum ultraviolet radiation.
AB  - We report the demonstration of a pulsed atomic lead (Pb) vapor-based vacuum
      ultraviolet frequency converter from 233 to 186 nm with unity photon-conversion
      efficiency. This conversion is attained without phase matching.

PMID- 18073805
TI  - Programmable axial apodizing and hyperresolving amplitude filters with a liquid
      crystal spatial light modulator.
AB  - Amplitude-transmitting filters for apodizing and hyperresolving applications can
      be easily implemented by use of a two-dimensional programmable liquid-crystal
      spatial light modulator operating in a transmission-only mode. Experimental
      results are in excellent agreement with theoretical predictions. This approach
      can permit the analysis of various filter designs and can allow the filters to be
      changed rapidly to modify the response of an optical system.

PMID- 18073806
TI  - Semiconductor saturable-absorber mirror assisted Kerr-lens mode-locked
      Ti:sapphire laser producing pulses in the two-cycle regime.
AB  - Pulses of sub-6-fs duration have been obtained from a Kerr-lens mode-locked
      Ti:sapphire laser at a repetition rate of 100 MHz and an average power of 300 mW.
      Fitting an ideal sech(2) to the autocorrelation data yields a 4.8-fs pulse
      duration, whereas reconstruction of the pulse amplitude profile gives 5.8 fs. The
      pulse spectrum covers wavelengths from above 950 nm to below 630 nm, extending
      into the yellow beyond the gain bandwidth of Ti:sapphire. This improvement in
      bandwidth has been made possible by three key ingredients: carefully designed
      spectral shaping of the output coupling, better suppression of the dispersion
      oscillation of the double-chirped mirrors, and a novel broadband semiconductor
      saturable-absorber mirror.

PMID- 18073807
TI  - Experimental validation of a technique to measure tilt from a laser guide star.
AB  - We have experimentally demonstrated for what is believed to be the first time a
      method for sensing wave-front tilt with a laser guide star (LGS). The tilt
      components of wave fronts were measured synchronously from the LGS by use of a
      telescope with a 0.75-m effective aperture and from the star Polaris by use of a
      1.5-m telescope. The Rayleigh guide star was formed at an altitude of 6 km and at
      a corresponding range of 10.5 km by projection of a focused beam at Polaris from
      the full aperture at the 1.5-m telescope. Both telescope mounts were unpowered
      and bolted in place, allowing us to reduce substantially the telescope vibration.
      The maximum value of the measured cross-correlation coefficient between the tilt
      for Polaris and the LGS is 0.71. The variations of the measured cross-correlation
      coefficient in the range from 0.22 to 0.71 are caused by turbulence at altitudes
      above 6 km, which was not sampled by the laser beacon but affected tilt for
      Polaris, the cone effect for turbulence below 6 km, residual mount jitter of the
      telescopes, and variations of the signal/noise ratio. The results support our
      concept of sensing atmospheric tilt by observing a LGS with an auxiliary
      telescope and indicate that this method is a possible solution for the tip-tilt
      problem.

PMID- 18073808
TI  - Beam-propagation factor and mode-coherence coefficients of hyperbolic-cosine
      Gaussian beams.
AB  - Analytical expressions for the M(2) factor and the mode-coherence coefficients of
      hyperbolic-cosine- (cosh-) Gaussian beams have been derived, and a simple method
      of producing cosh-Gaussian beams in an experiment, superposition of two
      decentered Gaussian beams, has been proposed. Our results will be useful for
      studying more-general Hermite-sinusoidal-Gaussian beams.

PMID- 18073809
TI  - Observation of a modulation effect caused by a microsphere resonator strongly
      coupled to a dielectric substrate.
AB  - The effect of modulation caused by a microsphere resonator is experimentally
      investigated with a model system consisting of a microsphere resonator and a
      plane substrate. We used total internal reflection microscopy (TIRM), which is a
      combination of conventional optical microscopy and the total internal reflection
      method, and observed the intensity distribution under the resonator in the
      evanescent-wave incidence condition. The TIRM patterns drastically change when
      the wavelength of the incident beam is scanned across a resonance. The response
      of the system is discussed on the basis of a recent proposal of traveling-wave
      resonance.

PMID- 18073810
TI  - Fabrication of long-period fiber gratings by focused irradiation of infrared
      femtosecond laser pulses.
AB  - We have fabricated long-period fiber gratings by use of a novel technique using
      focused irradiation of infrared femtosecond laser pulses. We investigate the
      thermal stability of the fabricated fiber gratings. The values of the loss peak
      wavelength and the transmittance of the fiber gratings after heat treatment below
      500 degrees C are the same as initial values before heat treatment. The fiber
      gratings that were fabricated by this technique have a high resistance to thermal
      decay. We propose that this technique will be useful for fabrication of fiber
      gratings with a superior aging characteristic.

PMID- 18073811
TI  - Polarization recording and reconstruction in Disperse Red 1 -doped cellulose
      acetate.
AB  - Cellulose acetate films doped with the azo dye Disperse Red 1 were prepared by
      dip coating. This matrix provides holograms of comparable efficiency for gratings
      recorded by intensity and polarization modulations. We used this matrix to store
      and successfully reconstruct the polarization state of an elliptically polarized
      object beam. A single plane-polarized reference beam was used for both recording
      and reconstruction.

PMID- 18073812
TI  - Multiplexing holograms in LiNbO3:Fe:Mn crystals.
AB  - Persistent holograms are recorded with red light in lithium niobate crystals
      doped with manganese and iron. Different erasure mechanisms are investigated, and
      a recording schedule for multiplexing holograms with equal diffraction
      efficiencies is proposed. To test the recording schedule experimentally, we
      multiplex 50 plane-wave holograms with the proposed recording schedule.

PMID- 18073813
TI  - Waveguide grating coupler with a tailored spectral response based on a computer
      generated waveguide hologram.
AB  - We propose a novel method that, for the first time to our knowledge, makes it
      possible to tailor the spectral response of an input grating coupler. This method
      is based on the idea of computer-generated waveguide holography. Grating couplers
      with different spectral responses have been designed and fabricated, and
      experimental results are presented that demonstrate the effectiveness of the
      proposed method.

PMID- 18073814
TI  - Photopolymer-filled nanoporous glass as a dimensionally stable holographic
      recording medium.
AB  - The holographic recording characteristics of a photopolymer-nanoporous-glass
      composite are reported. An M/# of 3.2 is measured in this medium by angle
      multiplexing of a series of plane-wave holograms. In addition, the dimensional
      stability of the material is demonstrated by the negligible Bragg detuning of a
      set of angle-multiplexed holograms recorded with varying grating tilt angles and
      by the relative insensitivity of the detuning to changes in temperature.

PMID- 18073815
TI  - Color-image generation by use of binary-phase holograms.
AB  - A novel, simple scheme for producing full-color images by use of binary-phase
      holograms and red (632.8-nm), green (543.5-nm), and blue (488-nm), lasers is
      reported. The theory and experimental results of the system are also presented.

PMID- 18073816
TI  - Two-dimensional multispecies imaging of a supersonic nozzle flow.
AB  - Raman imaging is shown to be a very suitable technique for simultaneous density
      mapping of different species in dry air and N(2) supersonic nozzle flows. The
      salient features of Raman scattering are its molecular sensitivity and the fact
      that it can be spectrally separated from strong reflections and Mie scattering.
      We collected Raman images of both N(2) and O(2) concurrently by imaging the flow
      through an imaging spectrograph with a broad entrance slit onto a CCD camera. The
      main advantage of this method is that different species can be imaged under
      exactly the same flow conditions.

PMID- 18073817
TI  - High-sensitivity detection of CH radicals in flames by use of a diode-laser-based
      near-ultraviolet light source.
AB  - CH radical distributions in ethylene-air and methane-air diffusion flames are
      mapped by wavelength-modulation absorption spectroscopy (WMS). Tunable,
      wavelength-modulated 426-nm light is generated by frequency doubling of a
      modulated 852-nm distributed Bragg reflector diode laser. Absorbances of 5 x 10(
      5) are measured with second-harmonic (2f) WMS with a signal-to-noise ratio of 3:1
      in a 3-Hz measurement bandwidth. The feasibility of simultaneous line-of-sight
      absorption and spatially resolved laser-induced-fluorescence detection with a
      single excitation beam is also demonstrated. This near-UV source is suitable for
      microgravity drop-tower experiments and other applications in which compact,
      rugged, energy-efficient instrumentation is required.

PMID- 18073818
TI  - Interferometry with optical pickups.
AB  - We describe an interferometer that makes use of an optical pickup. This
      widespread consumer electronics component has a high degree of technological
      content. A typical head contains a remarkable, highly integrated sample of
      optoelectronic laboratory equipment. The application that we report is a
      significant and novel example of the potential exploitation of the unique
      features of such a device for scientific aims. Many interferometric
      configurations can be envisaged, depending on the specific pickup design. We
      present a Fizeau multiphase homodyne interferometer that makes use of an
      astigmatic-focus-detection pickup. Its quadrant detector provides four
      photocurrent signals whose phase delays can be easily controlled. This allows us
      to apply phase-shifting interferometry algorithms for data reduction.

PMID- 18073819
TI  - Highly efficient 4-W Yb-doped fiber amplifier pumped by a broad-stripe laser
      diode.
AB  - A Yb-doped double-cladding fiber amplifier is v-groove side pumped by a 100
      microm -wide, broad-stripe, 975-nm laser diode. The amplifier exhibits,
      separately, 39% electrical-to-optical conversion efficiency, 89% internal optical
      to-optical conversion efficiency, 4-W output power at 1060 nm, and a small-signal
      gain of 53 dB.

PMID- 18073820
TI  - Widely tunable, narrow-linewidth, subnanosecond pulse generation in an
      electronically tuned Ti:sapphire laser.
AB  - Widely tunable subnanosecond Ti:sapphire laser radiation pumped with a cw Q 
      switched laser-diode-pumped Nd:YAG laser has been demonstrated in a simple laser
      system with a configuration of variable cavity length. Laser wavelengths can be
      continuously tuned by adjustment of the rf of an intracavity acousto-optic
      tunable filter with a computer through the whole range of the laser gain. During
      tuning of the whole spectral range, there is no need to realign any optics in the
      laser, except for moving the mirror to track the change of the rf. The peak
      powers of the output pulses at a pump level of 300 mW are comparable with those
      of conventional tunable picosecond Ti:sapphire lasers at a cw pump level of
      almost 10 W.

PMID- 18073821
TI  - 208-W TEM00 operation of a diode-pumped Nd:YAG rod laser.
AB  - 208-W average-power TEM(00) -mode operation from a diode-pumped Nd:YAG rod laser
      was demonstrated. The side-pumping method of generating a high-gain aberration
      free rod, the bifocusing-compensation technique with two identically pumped rods,
      and a suitable choice of beam spot size were employed in the design of this
      laser. At the maximum pump power of 1.1 kW the fundamental transverse-mode
      operation (M(2)<1.1) was characterized by 7.6% electrical efficiency. The
      extraction efficiency was almost 60% of full multimode operation. Stable
      operation was obtained within a pump-power range of 15% of the maximum pump
      power.

PMID- 18073822
TI  - Chemical silver coating of fiber tips in near-field scanning optical microscopy.
AB  - We report what is believed to be the first experimental demonstration of silver
      coating by a wet chemical process on tapered fiber tips used in near-field
      scanning optical microscopy. The process occurs at room temperature and pressure
      and takes only a few minutes to complete. Many tips can be coated simultaneously.

PMID- 18073823
TI  - Nonlinear propagation effects in an AlGaAs Bragg grating filter.
AB  - We present experimental observations of nonlinear propagation effects in an
      integrated AlGaAs waveguide filter. We demonstrate pulse shaping, pulse
      compression, and the production of gap solitons within the stop band of the
      grating for switching powers of approximately 130 W . This nonlinear behavior is
      associated with the counterbalancing effects of self-phase modulation and the
      large dispersion effects introduced by the grating itself.

PMID- 18073824
TI  - Infrared laser spectroscopic imaging based on degenerate four-wave-mixing
      spectroscopy combined with frequency-upconversion detection.
AB  - Frequency-upconversion detection of an infrared degenerate four-wave-mixing image
      was proposed for infrared laser spectroscopic imaging of species in the gas
      phase. The operation of the imaging system has been demonstrated by observation
      of an expanding Cs plume generated by laser ablation.

PMID- 18073825
TI  - 1 W of blue 465-nm radiation generated by frequency doubling of the output of a
      high-power diode laser in critically phase-matched LiB3O5.
AB  - Blue 465-nm radiation is generated by frequency doubling of the output of an
      InGaAs diode-laser oscillator-amplifier system in critically phase-matched
      LiB(3)O(5) (LBO). The diode-laser system emitted 4 W of single-frequency 930-nm
      radiation in a near-diffraction-limited beam (M(2)<1.2) . The laser power is
      enhanced to values of up to 150 W in a resonant external ring cavity. The LBO
      crystal is placed at a resonator internal focus. The frequency doubling in the
      LBO crystal generates blue radiation at 465 nm with a power of 1 W. The spectral
      width of the blue radiation is less than 3 MHz, and the value of the M(2) beam
      parameter is less than 1.2.

PMID- 18073826
TI  - Polarization controller using nematic liquid crystals.
AB  - In this Letter we demonstrate a polarization controller capable of changing any
      state of polarization of light from one arbitrary state to another. The
      controller consists of a stack of three homogeneous nematic liquid-crystal cells.
      The polarization state is controlled by proper adjustment of the voltages applied
      across each of the cells. The mathematical algorithm and principles of this
      polarization controller are developed in the framework of the Stokes parameters,
      allowing easy visualization by use of a Poincare sphere representation. The
      transformation functions are given for conversion of an arbitrary input state to
      any output state. Experiments are carried out to demonstrate arbitrary
      polarization transformation.

PMID- 18073828
TI  - Observation of satellite peaks and dips in the scattering of light in a double
      pass geometry.
AB  - We report the experimental observation of enhanced backscattering and satellite
      peaks and dips in light scattered by a system that involves double passage of
      waves through a random-phase screen and a birefringent crystal.

PMID- 18073827
TI  - Intense 8-fs pulse generation in the deep ultraviolet.
AB  - By use of the recently developed technique of guided-wave frequency conversion,
      the generation of sub-10-fs light pulses in the UV has been demonstrated for what
      is believed to be the first time. Cross-phase modulation of the light in a hollow
      waveguide produced a bandwidth of 16 nm, with a center frequency of 270 nm, at 1
      kHz. A simple grating pair was used to compress the pulses to a duration of 8 fs,
      as measured by self-diffraction frequency-resolved optical gating. In the
      experiment the compressed energy was greater than 1 muJ , with a peak power of
      >100 MW ; the technique can be scaled to higher energy. Further improvements
      should make it possible to generate pulses as short as approximately 3 fs with
      this technique.

PMID- 18073829
TI  - Nearly isotropic photonic bandgap structures in two dimensions.
AB  - It is suggested that a material with a novel spatial dielectric distribution can
      exhibit a bandgap that is approximately independent of propagation angle. This
      independence is accomplished by development of the dielectric constant from
      reflection vectors of equal strength that are ideally equispaced in angle.

PMID- 18073830
TI  - Coupled-resonator optical waveguide: a proposal and analysis.
AB  - We propose a new type of optical waveguide that consists of a sequence of coupled
      high-Q resonators. Unlike other types of optical waveguide, waveguiding in the
      coupled-resonator optical waveguide (CROW) is achieved through weak coupling
      between otherwise localized high-Q optical cavities. Employing a formalism
      similar to the tight-binding method in solid-state physics, we obtain the
      relations for the dispersion and the group velocity of the photonic band of the
      CROW's and find that they are solely characterized by coupling factor k(1) . We
      also demonstrate the possibility of highly efficient nonlinear optical frequency
      conversion and perfect transmission through bends in CROW's.

PMID- 18073831
TI  - Enhanced thermal and magnetic actuations for broad-range tuning of fiber Bragg
      grating based reconfigurable add drop devices.
AB  - We demonstrate two new approaches to broad-range tuning of fiber Bragg grating
      devices: amplified thermal tuning and programmable magnetic tuning. The thermal
      strain tuning approach employs a novel configuration to amplify thermally induced
      wavelength shifts by use of a negative thermal-expansion component. The magnetic
      strain tuning approach allows programmable and latchable wavelength shifts
      through magnetic interactions that induce controlled strain on the fiber grating.
      The advantages and disadvantages of these two techniques are contrasted.

PMID- 18073832
TI  - Optical clock repetition-rate multiplier for high-speed digital optical logic
      circuits.
AB  - Repetition-rate multiplication has been shown by use of a fiber ring oscillator
      with a semiconductor optical amplifier as the gain medium and by use of fast
      saturation and recovery of the amplifier from an external optical pulse train.
      Repetition-frequency multiplication up to 6 times and up to 34.68-GHz frequency
      have been achieved.

PMID- 18073833
TI  - Feasibility of 1-Tbit/s (25 x 40 Gbit/s) transoceanic optically regenerated
      systems.
AB  - The feasibility of 1-Tbit/s transoceanic systems based on in-line optical
      regeneration of 40-Gbit/s channels is numerically investigated. The roles of
      fiber dispersion, fiber mode area, and channel and regenerator spacings are
      analyzed, and the corresponding operating ranges for error-free transmission are
      determined. The results represent a first step in designing multi-terabit-per
      second global transmission systems based on realistic components and parameters.

PMID- 18073834
TI  - Pigtailing the high-Q microsphere cavity: a simple fiber coupler for optical
      whispering-gallery modes.
AB  - We demonstrate a simple method for efficient coupling of standard single-mode
      optical fibers to a high- Q optical microsphere cavity. Phase-matched excitation
      of whispering-gallery modes is provided by an angle-polished fiber tip in which
      the core-guided wave undergoes total internal reflection. In the experimental
      setup, which included a microsphere with both an input and an output coupler, the
      total fiber-to-fiber transmission at resonance reached 23% (total insertion loss,
      6.3 dB), with loaded quality factor Q> or =3 x 10(7) and unloaded Q approximately
      1.2 x 10(8) at 1550 nm. A simple pigtailing method for microspheres permits their
      wider use in fiber optics and photonics devices.

PMID- 18073835
TI  - Polarization-insensitive nonlinear optical loop mirror demultiplexer with twisted
      fiber.
AB  - We experimentally demonstrate reduction of the polarization sensitivity of a
      nonlinear optical loop mirror (NOLM) from 5 to 0.5 dB by use of 550 m of twisted
      dispersion-shifted fiber with a twist rate of 8 turns/m (24 turns/beat length).
      The twisting of the fiber induces circular birefringence and equates the parallel
      and the orthogonal-polarization nonlinear phase-shift terms. Experimental results
      show that the polarization sensitivity monotonically decreases from 5 dB for
      nontwisted fiber to 0.5 dB for fiber that is twisted at a rate of 8 turns/m, and
      the twist rate should be more than 4 turns/m (>10 turns/beat length) for
      emulation of circularly polarized fiber. The minimum polarization sensitivity
      occurs when the control-pulse polarization is aligned with one of the eigenmodes
      of the twisted fiber. With the fiber twisted at a rate of 8 turns/m in the NOLM,
      the nonlinear transmission is 23% at a switching energy of 4 pJ/pulse.
      Simulations confirm the observed behavior and show that the remaining
      polarization sensitivity results from energy transfer between orthogonal modes of
      the signal pulse.

PMID- 18073836
TI  - Photochemical reaction of hydrogen with germanosilicate glass initiated by 3.4
      5.4-eV ultraviolet light.
AB  - By measuring the photosensitivity of Ge-doped silica fibers over the 3.4-5.4-eV
      spectral range and from T=95 K to T=375 K , we demonstrate that different
      physical mechanisms take place depending on whether H(2) is present. Without H(2)
      the principal photosensitivity pathway involves excitation of a germanium oxygen
      deficient center to its triplet state. In H(2) -loaded fibers the UV light
      excites the regular Ge-O bond, which then reacts with H(2) to produce Si-OH or Ge
      OH and a GeE(') center.

PMID- 18073837
TI  - Soliton optical phase control by use of in-line filters.
AB  - We address the problem of soliton phase jitter caused by fiber amplifier noise in
      a communication channel. An analytical expression for phase jitter is derived by
      use of perturbation theory. In the absence of filters the variance of the phase
      is found to be proportional to the cube of the propagation distance, but it
      increases only linearly if in-line filters are used. We verify with simulations
      that in-line filters maintain the phase jitter at a level that is tolerable for
      transoceanic links.

PMID- 18073838
TI  - Solitarylike Raman states in massive wavelength-division-multiplexed systems.
AB  - We show that solitarylike stimulated Raman excitations are possible in massive
      wavelength-division-multiplexed fiber-optic systems. These self-similar states
      can propagate across channels at a constant rate that depends on the total power
      launched in the system and the wave's spectral width. The evolution of these
      excitations under the action of noise and during collisions is investigated in
      detail.

PMID- 18073839
TI  - Nondispersive wavelength-division sampling.
AB  - We propose and demonstrate a new wavelength-division-sampling technique with high
      temporal resolution. A discrete-time true-time delay generates multiwavelength
      near-transform-limited pulses from a supercontinuum source. Pulses sample the
      analog signal in an electro-optic modulator and are subsequently demultiplexed in
      a wavelength-division-multiplexing filter. A 100-Gsample/s experimental
      demonstration of this concept is presented.

PMID- 18073840
TI  - Effective point-spread function for fast image modeling and processing in
      microscopic imaging through turbid media.
AB  - An effective point-spread function (EPSF) for microscopic imaging through turbid
      media is proposed and calculated. The EPSF incorporates the property of a
      microscope system as well as the scattering property of a turbid medium. We prove
      that the image of a thin object embedded in a turbid medium can be expressed by
      the convolution of the EPSF with an object function. With the help of the
      convolution relation, image modeling for 5, 000, 000 incident photons can be
      approximately 15 times faster than the direct Monte Carlo simulation method for a
      one-dimensional object and can be at least 2 orders of magnitude faster for a two
      dimensional object.

PMID- 18073841
TI  - Laser optical feedback tomography.
AB  - We describe a new method for imaging in three-dimensional turbid media, laser
      optical feedback tomography. This technique is based on the resonant sensitivity
      of a short-cavity laser to frequency-shifted optical feedback from ballistic
      photons retrodiffused from the medium. The advantage of the method is that the
      detector is the laser source itself, which provides optical amplification with
      self-aligned spatial and temporal coherent detection.

PMID- 18073842
TI  - Near-field imaging of the interference pattern of counterpropagating evanescent
      waves.
AB  - It is generally accepted that measurement of the contrast of the intensity
      interference pattern formed by two counterpropagating evanescent waves can be
      used to characterize the resolving power of a collection near-field microscope.
      We argue that, if the light collected by a fiber probe propagates toward a
      detector in the form of guided fiber modes, then this perception is wrong. Using
      symmetry arguments and simple calculations, we show that, if an extended fiber
      probe is axially symmetric and oriented perpendicular to the propagation
      direction, then the measured contrast should always be equal to the contrast of
      the interference pattern.

PMID- 18073843
TI  - Laser operation with nearly diffraction-limited output from a Yb:YAG multimode
      channel waveguide.
AB  - We report laser action of a crystal channel-waveguide laser consisting of a
      diffusion-bonded Yb:YAG-YAG core-cladding structure. By use of diode bars a side
      pumped arrangement adapted to the channel-waveguide geometry was realized,
      resulting in up to 1-W output power and a low threshold. With a rectangular core
      with a 100-mum cross section, nearly diffraction-limited performance is
      demonstrated. The influence of the guiding properties of the channel waveguide on
      the resonator mode was studied with a nearly concentric resonator.

PMID- 18073844
TI  - Self-starting Nd:YAG holographic laser oscillator with a thermal grating.
AB  - Self-starting operation of a self-conjugating loop oscillator is achieved, for
      the first time to our knowledge, by use of an optically induced thermal hologram
      in a nonsaturable absorbing medium. Self-Q-switched single-longitudinal-mode
      pulses of 12-ns duration are obtained in a near-diffraction-limited spatial mode
      and with an output energy of >250 mJ . Good correction of intracavity phase
      distortions is obtained, as well as good extraction efficiency in the laser mode
      volume. It is shown that one has to set an additional nonreciprocal phase-shift
      element in the loop to ensure resonant operation of the system.

PMID- 18073845
TI  - Two-photon absorption-induced self-phase modulation in GaAs-AlGaAs waveguides for
      surface-emitted second-harmonic generation.
AB  - Performance-limiting asymmetric distortion is observed in the spectra of
      fundamental pulses transmitted through GaAs-Al(0.9)Ga(0.1)As multilayer
      waveguides designed for surface-emitted second-harmonic generation. This behavior
      is attributed to refractive-index changes resulting from the accumulation of free
      carriers created by two-photon absorption in the GaAs layers. Numerical
      simulations of the intensity-dependent spectra by use of the separately measured
      two-photon absorption coefficient are shown to be in good agreement with the
      observed spectra.

PMID- 18073846
TI  - Spatial optical solitons resulting from multistep cascading.
AB  - We introduce a novel class of parametric optical solitons supported
      simultaneously by two second-order nonlinear cascading processes, second-harmonic
      generation and sum-frequency mixing. We obtain analytical and numerical solutions
      for three-wave spatial solitons and show that the presence of an additional
      cascading mechanism can change dramatically the properties and stability of two
      wave quadratic solitary waves.

PMID- 18073847
TI  - Encrypted optical memory system using three-dimensional keys in the Fresnel
      domain.
AB  - An encrypted optical memory system using double random phase codes in the Fresnel
      domain is proposed. In this system, two random phase codes and their positions
      form three-dimensional keys for encryption of images and are used as keys to
      recover the original data. The third dimension is the positions of the codes,
      which can have as many as three degrees of freedom. Original images encrypted by
      use of the two phase codes located in the Fresnel domain are stored
      holographically in a photorefractive material. We demonstrate in preliminary
      experiments encryption and decryption of optical memory in a LiNbO(3) :Fe
      photorefractive crystal by use of angular multiplexing.

PMID- 18073848
TI  - High-density wavelength switching obtained from a tunable multisection laser
      diode.
AB  - We describe a method based on multistability in wavelength for obtaining high
      density wavelength switching for application to signal routing. The method relies
      on the use of a 1550-nm wavelength-tunable multielectrode laser diode that is fed
      back electrically. The system operates as a multistable device that exhibits
      multiple steady states in wavelength. The device can be used to convert time
      multiplexed packets into wavelength-multiplexed signals.

PMID- 18073849
TI  - Stable single-mode vertical-cavity surface-emitting laser with a photoresistive
      aperture.
AB  - It is numerically demonstrated that on-axis current channeling through the use of
      a photoactive layer or layers in vertical-cavity surface-emitting laser cavities
      counteracts hole burning and allows single-mode operation at high currents. The
      photoactive layers act as a variable-resistivity screen whose radial aperture is
      controlled by the light itself. Absorption of a small fraction of the light
      intensity suffices for significant on-axis current peaking with minimum
      efficiency loss and optical mode distortion.

PMID- 18073850
TI  - Microcavities combining a semiconductor with a fused-silica microsphere.
AB  - We report studies of a novel microcavity system that combines a semiconductor
      quantum well with a fused-silica microsphere. We show that excitonic
      photoluminescence from the quantum well couples efficiently into whispering
      gallery modes. Using a resonant light-scattering technique, we demonstrate that
      the Q factor of the combined system exceeds 10(5) . Our studies also point to the
      necessity of using semiconductor nanostructures with a capping layer no more than
      a few nanometers thick.

PMID- 18073851
TI  - Photon-number squeezing in the normal-dispersion regime.
AB  - We experimentally demonstrate the generation of amplitude-squeezed light in the
      normal-dispersion regime and measure by direct detection 1.7+/-0.1 dB (33%) and,
      with correction for linear losses, 2.5+/-0.2 dB (47%) of noise reduction below
      the shot-noise level. The dependence of the noise behavior on dispersion is
      investigated both experimentally and theoretically.

PMID- 18073852
TI  - Characterization of sub-10-fs pulse focusing with high-numerical-aperture
      microscope objectives.
AB  - Dispersion precompensation with a prism sequence and a third-order dispersion
      mirror resulted in negligible broadening of sub-10-fs pulses at subwavelength
      spot sizes when the pulses were focused with microscope objectives and moderate
      apertures. At larger apertures, lens chromaticity and spherical aberration led to
      an effective pulse broadening of up to 1.3x , depending on the aperture size and
      the detector position. The data suggest that intensities exceeding 10(14) W/cm(2)
      can be produced directly from femtosecond pulse oscillators.

PMID- 18073853
TI  - Generation of 12-fs pulses from a diode-pumped Kerr-lens mode-locked Cr:LiSAF
      laser.
AB  - We demonstrate 12-fs-pulse generation from a diode-pumped Kerr-lens mode-locked
      Cr:LiSAF laser. This is to our knowledge the shortest pulse ever produced from a
      mode-locked Cr:LiSAF laser. Based on an improved estimation of the intracavity
      dispersions, we utilized BK7 glass for the Brewster-prism-pair material.

PMID- 18073854
TI  - Upconversion time microscope demonstrating 103 x magnification of femtosecond
      waveforms.
AB  - We present the operational principles and results of a temporal imaging system,
      configured as a time microscope, that achieves 103 x magnification of waveforms
      with 300-fs resolution and a 5.7-ps field of view. The quadratic-phase time-lens
      element is realized by upconversion of the dispersed input waveform with a
      linearly chirped 5-THz bandwidth pump. The system allows expansion of ultrafast
      optical waveforms to a time scale that is directly accessible with slower
      conventional technology, in real time, on a single-shot basis.

PMID- 18073855
TI  - Infrared femtosecond laser pulse induced permanent reduction of Eu3+ to Eu2+ in a
      fluorozirconate glass.
AB  - We report what is believed to be the first observation of permanent
      photoreduction of Eu(3+) to Eu(2+) in transparent and colorless Eu(3+) -doped
      fluorozirconate glass at room temperature, using an infrared femtosecond laser.
      Difference absorption and electron-spin-resonance spectra of the glass before and
      after laser irradiation showed that a portion of the Eu(3+) ions in the focused
      part of the laser inside the glass were reduced to Eu(2+) ions after laser
      irradiation. It is suggested that Eu(3+) ions act as electron-trapping centers,
      whereas active sites in the glass matrix act as hole-trapping centers, leading to
      the formation of Eu(2+) ions. The observed phenomenon is inferred to be useful in
      the fabrication of optical memory devices with high storage density and waveguide
      type micro-optical devices.

PMID- 18073856
TI  - Enhancement of second-harmonic generation with femtosecond laser pulses near the
      photonic band edge for different polarizations of incident light.
AB  - We present experimental evidence of enhancement of second-harmonic generation as
      a result of an increase of the fundamental-field energy density within a
      multilayer structure near the photonic band edge.

PMID- 18073857
TI  - Reflection and transmission coefficients for diffuse photon density waves.
AB  - Diffuse photon density waves are proposed for use in characterizing diffuse
      media, similar to the use of electromagnetic waves to characterize reflection
      from materials. To this end basic expressions for the reflection and transmission
      coefficients at interfaces are put forward. Effects such as the existence of
      modes analogous with Brewster modes are shown. Also, we illustrate through
      numerical simulations how the diffusion optical parameters are estimated both
      with and without noise in the data.

PMID- 18073858
TI  - High-speed soliton transmission in dense periodic fibers.
AB  - An 80-Gbit/s soliton can be transmitted over a cross-Pacific distance in a dense
      periodic fiber, even in the presence of higher-order effects. Such a dense
      dispersion-managed soliton is generally more stable and faces fewer mutual
      interactions than a conventional dispersion-managed soliton.

PMID- 18073859
TI  - 10-Gbit/s dispersion-managed soliton transmission over 16,500 km in standard
      fiber by reduction of soliton interactions.
AB  - We show experimentally and numerically that in high-speed strongly dispersion
      managed standard fiber soliton systems nonlinear interactions limit the
      propagation distance. We present results that show that the effect of these
      interactions can be significantly reduced by appropriate location of the
      amplifier within the dispersion map. Using this technique, we have been able to
      extend the propagation distance of 10-Gbit/s 2(31)-1pseudorandom binary sequence
      soliton data to 16, 500 km over standard fiber by use of dispersion compensation.
      To our knowledge this distance is the farthest transmission over standard fiber
      without active control ever reported, and it was achieved with the amplifier
      placed after the dispersion-compensating fiber in a recirculating loop.

PMID- 18073860
TI  - Single and double distributed optical amplifier fiber bus networks with
      wavelength-division multiplexing for photonic sensors.
AB  - Two different optical fiber bus networks are compared and demonstrated
      experimentally as means of gathering information from four wavelength-division
      multiplexed photonic sensors. Both topologies include distributed amplification,
      which allows one to overcome the limitation in the maximum number of sensors that
      can be multiplexed in a single structure. Results obtained with a dual-bus
      topology are compared with those achieved with a single-bus network.

PMID- 18073861
TI  - Influence of the Raman effect on dispersion-managed solitons and their
      interchannel collisions.
AB  - We calculate the self-frequency shift experienced by a soliton in a dispersion
      managed fiber that is due to the Raman effect, as well as the energy and
      frequency shifts that result from a collision of such solitons with different
      wavelengths. We find that dispersion management suppresses both types of
      frequency shift but does not significantly affect the energy shift that is
      accumulated over a large propagation distance. The latter shift may represent a
      potential problem for wavelength-division-multiplexed systems with several
      gigabits per second in a single channel.

PMID- 18073862
TI  - Confocal microscopy with a volume holographic filter.
AB  - We describe a modified confocal microscope in which depth discrimination results
      from matched filtering by a volume hologram instead of a pinhole filter. The
      depth resolution depends on the numerical aperture of the objective lens and the
      thickness of the hologram, and the dynamic range is determined by the diffraction
      efficiency. We calculate the depth response of the volume holographic confocal
      microscope, verify it experimentally, and present the scanned image of a silicon
      wafer with microfabricated surface structures.

PMID- 18073863
TI  - Snake-based method for the segmentation of objects in multichannel images
      degraded by speckle.
AB  - We recently proposed a new approach for the segmentation of speckled images based
      on active contours (snakes) [e.g., Opt. Commun. 137, 382 (1997)]. We propose an
      extension of this approach to multichannel data. Two solutions are compared based
      on hypotheses on the possible mean intensity variation between the channels. Each
      solution is optimal for a certain class of input images, but one solution shows
      better or equivalent performance for both input image classes. This result opens
      new perspectives for the segmentation of multichannel images with the snake-based
      approach.

PMID- 18073864
TI  - Two-dimensional colloidal crystal corrugated waveguides.
AB  - We demonstrate, for what is to our knowledge the first time, two-dimensional (2D)
      corrugated waveguides at optical wavelengths obtained by use of 2D colloidal
      crystals. We report experimental studies of light coupling into and out of the
      waveguide structure. The diffracted light shows interesting optical properties
      that exist only in such 2D grating structures. Field distribution of the
      fundamental mode in the structure is studied by use of a simplified model in our
      analysis. Potential applications of this type of structure are discussed.

PMID- 18073865
TI  - Simple method for reducing the depolarization loss resulting from thermally
      induced birefringence in solid-state lasers.
AB  - A simple technique for reducing the loss that is due to depolarization resulting
      from thermally induced stress birefringence in solid-state lasers is reported.
      The technique uses a single intracavity quarter-wave plate with its fast or slow
      axis aligned parallel to the preferred plane of polarization, defined by an
      intracavity polarizer. This technique has been applied to a diode-bar-pumped
      Nd:YAG laser operating at 946 nm, resulting in a measured reduction in
      depolarization loss from approximately 1.7% to approximately 0.0006% and yielding
      a diffraction-limited, TEM(00) , linearly polarized output power of 2.9 W for an
      incident pump power of 14.3 W.

PMID- 18073866
TI  - High-power 390-nm laser source based on efficient frequency doubling of a tapered
      diode laser in an external resonant cavity.
AB  - We frequency doubled the single-frequency beam from an external-cavity tapered
      laser diode operating at 780 nm in a resonant cavity containing a beta -barium
      borate crystal to generate an output at 390 nm with high efficiency. Output
      powers as great as 233 mW were obtained, corresponding to an efficiency of 65%/W
      . The resonant-cavity design was a low-loss three-mirror configuration that
      provided compensation for astigmatism and coma. The laser diode frequency was
      locked to the doubling-cavity resonance by use of the Hansch-Couillaud
      discrimination technique.

PMID- 18073867
TI  - High-sensitivity intracavity laser absorption spectroscopy with vertical-external
      cavity surface-emitting semiconductor lasers.
AB  - We report the demonstration of high-sensitivity intracavity laser absorption
      spectroscopy with multiple-quantum-well vertical-external-cavity surface-emitting
      semiconductor lasers (VECSEL's). A detection limit of 3 x 10(-10) cm (-1) has
      been achieved. The spectrotemporal dynamics of a VECSEL in the 1030-nm wavelength
      region has been studied. The laser was operating cw at room temperature, with a
      baseline signal-to-noise ratio as high as 400. The laser was optically pumped
      with a threshold as low as 80 mW and was broadly tunable over a spectral range of
      approximately 75 nm .

PMID- 18073868
TI  - Noninvasive optical method of measuring tissue and arterial saturation: an
      application to absolute pulse oximetry of the brain.
AB  - We present a frequency-domain optical method for real-time noninvasive
      measurement of absolute tissue and arterial saturation. This method is based on
      quantitative measurement of the tissue absorption spectrum (for tissue
      saturation) and of the amplitude of the arterial-pulsation-induced absorption
      oscillations (for arterial saturation) at eight wavelengths in the range 633-841
      nm. We report results obtained from readings taken from the forehead of a healthy
      volunteer, showing baseline saturation values of 74.7+/-0.2% (tissue) and 96.9+/
      0.5% (arterial). These values dropped to minimum values of 71.6+/-0.2% and 90.0+/
      0.2% , respectively, after 1 min of reduced inspired oxygen concentration [10%
      (by volume) O(2) from a baseline value of 21% O(2) ].

PMID- 18073869
TI  - Polarization self-modulation of the nonstationary speckle field in a
      photorefractive crystal.
AB  - We have observed the nonstationary polarization modulation of a speckle pattern
      transmitted through a photorefractive crystal under the alternating electric
      field of a square-wave form. A simple model based on Gaussian-beam propagation in
      the crystal with the diffusion type of nonlinearity is proposed to explain the
      main features of the experiment. Application of the phenomenon to noncontact and
      highly sensitive measurements of a rough surface movement is suggested.

PMID- 18073870
TI  - Quadratic solitary waves in a counterpropagating quasi-phase-matched
      configuration.
AB  - We demonstrate the possibility of self-trapping of optical beams by use of quasi
      phase matching in a counterpropagating configuration in quadratic media. We also
      show the predominant stability of these beams and estimate the power level
      required for their observation.

PMID- 18073871
TI  - Converting Eu3+ between defect sites in BaFCl for persistent spectral hole
      burning.
AB  - Persistent spectral hole burning (PSHB) is demonstrated in the (7)F(0)-->(5)D(0)
      optical transition of Eu(3+) doped into crystals of BaFCl. For Eu(3+) ions at two
      different lattice sites, persistent holes can be burned at temperatures below 77
      K. The characteristics of the hole-burning process suggest that the observed PSHB
      effect is due to laser-excitation-induced site-to-site conversion. One type of
      Eu(3+) site is converted into another type of defect site. This process is not
      optically reversible, and holes can be erased only when the temperature increases
      to 150 K.

PMID- 18073872
TI  - Spatial light modulation with an azobenzene-doped polymer by use of biphotonic
      holography.
AB  - Spatial light modulation by use of a biphotonic holographic grating has been
      demonstrated in an azobenzene-doped polymer film. The mechanism of incoherent-to
      coherent optical conversion originates from the photoinduced trans <--> cis
      isomerization of azobenzene molecules by two color lights. It is also found that
      when the intensity of the blue beam is varied the output replica of the input
      information changes sign.

PMID- 18073873
TI  - Enhanced all-optical switching by use of a nonlinear fiber ring resonator.
AB  - We predict dramatically reduced switching thresholds for nonlinear optical
      devices incorporating fiber ring resonators. The circulating power in such a
      resonator is much larger than the incident power; also, the phase of the
      transmitted light varies rapidly with the single-pass phase shift. The combined
      action of these effects leads to a finesse-squared reduction in the switching
      threshold, allowing for photonic switching devices that operate at milliwatt
      power levels in ordinary optical fibers.

PMID- 18073874
TI  - Femtosecond time-resolved optical polarigraphy: imaging of the propagation
      dynamics of intense light in a medium.
AB  - A time-resolved imaging technique for visualizing ultrafast propagation dynamics
      of intense light pulses in a medium has been demonstrated. The method probes the
      instantaneous birefringence induced by a pulse in the medium. Through consecutive
      femtosecond snapshot images of intense femtosecond laser pulses propagating in
      air, ultrafast temporal changes in the two-dimensional spatial distribution of
      the optical pulse intensity were clearly seen.

PMID- 18073875
TI  - Femtosecond optical packet generation by a direct space-to-time pulse shaper.
AB  - We demonstrate femtosecond operation of a direct space-to-time pulse shaper in
      which there is direct mapping (no Fourier transform) between the spatial position
      of the masking function and the temporal position in the output waveform. We use
      this apparatus to generate trains of 20 pulses as an ultrafast optical data
      packet over an approximately 40-ps temporal window.

PMID- 18073877
TI  - Photochemical processes induced by 157-nm light in H(2)-impregnated glassy
      SiO(2):OH.
AB  - F(2) excimer-laser irradiation induces two major changes in SiO(2): OH glass
      impregnated with H(2) molecules. First, the vacuum-UV optical absorption edge is
      bleached, and the absorption at 157 nm decreases from 0.95 to 0.68 cm(-1) .
      Second, preexisting free SiOH groups and interstitial H(2) are photochemically
      converted to hydrogen-bonded hydroxyl groups. It is suggested that the bleaching
      of the UV-absorption edge is caused by a change of OH groups from a free to a
      hydrogen-bonded state and by photolysis of distorted Si-O bonds that are
      absorbing in the edge region.

PMID- 18073878
TI  - Polarized light-scattering measurements of dielectric spheres upon a silicon
      surface.
AB  - The polarization of light scattered into directions out of the plane of incidence
      by polystyrene latex spheres upon a silicon substrate was measured for p 
      polarized incident light. The experimental data show good agreement with
      theoretical predictions for three sizes of spheres. These results demonstrate
      that the polarization of light scattered by particles can be used to determine
      the size of particulate contaminants on silicon wafers. Theoretical models, based
      on successive degrees of approximation, indicate that the mean distance of a
      particle from the surface is the primary determinant of the scattered light
      polarization for small out-of-plane scattering angles.

PMID- 18073879
TI  - Reduced-power optical solitons in fiber lines with short-scale dispersion
      management.
AB  - We examine the properties of dispersion-managed (DM) solitons in fiber lines with
      dispersion-compensation period L much shorter than amplification distance Z(a) .
      DM solitons in systems with short-scale dispersion compensation have reduced
      power compared with DM solitons in previously studied regimes with L>/=Z(a) power
      (for the same local and average dispersion and the same pulse width). As a
      result, chirped DM soliton transmission with reasonably low power can be realized
      with shorter pulses when DM solitons in systems with large L/Z(a) ratios have
      energies that are too high to be used in practice.

PMID- 18073880
TI  - Mode-profile dependence of the electrostrictive response in fibers.
AB  - The transverse optical intensity profile in fibers affects the efficiency of
      acoustic mode excitation by the optical field and the subsequent response of the
      field to the excited acoustic modes. The magnitude of the electrostrictive
      nonlinear coefficient for a square-top intensity profile will exceed that of a
      Gaussian profile by a fact of 2. For current fiber designs the range of values
      for n(2str) at zero frequency is expected to vary from 0.43 to 0.71x10(
      16)cm(2)W(-1) based on mode profile alone. The relative contribution of
      electrostriction to the total nonlinear response (electrostrictive+Kerr) in
      fibers increases proportionately as the mode profile flattens.

PMID- 18073881
TI  - Jones matrix of polarization mode dispersion.
AB  - We describe how to calculate the Jones matrix transfer function of a fiber if its
      principal states of polarization and its differential group delay as functions of
      frequency are known. Using two counterexamples related to second-order
      polarization mode dispersion (PMD), we also show that a previous method used for
      the same purpose induces overestimation of second-order PMD effects by a factor
      of 2. Our new method is used to solve the problem for both counterexamples.

PMID- 18073882
TI  - Smear correction for frame transfer charge-coupled-device cameras.
AB  - A simple algorithm is described and demonstrated for the removal of smear from
      images obtained with a frame transfer CCD camera. The algorithm requires
      specification of only a single parameter, which is related to the ratio of the
      single-pixel charge-transfer time of the CCD and the image integration time. The
      smear parameter is determined experimentally by the requirement that smear
      corrected images of a focused laser spot be symmetric.

PMID- 18073883
TI  - Accurate measurement of large optical frequency differences with a mode-locked
      laser.
AB  - We have used the comb of optical frequencies emitted by a mode-locked laser as a
      ruler to measure differences of as much as 20 THz between laser frequencies. This
      is to our knowledge the largest gap measured with a frequency comb, with high
      potential for further improvements. To check the accuracy of this approach we
      show that the modes are distributed uniformly in frequency space within the
      experimental limit of 3.0 parts in 10(17) . By comparison with an optical
      frequency comb generator we have verified that the mode separation equals the
      pulse repetition rate within the experimental limit of 6.0 parts in 10(16).

PMID- 18073884
TI  - Tunable visible solid-state lasers based on intracavity frequency doubling of
      Cr:forsterite in KTP.
AB  - Broadband tunability in the yellow-red region is obtained by use of intracavity
      type II second-harmonic generation of gain-switched Cr:forsterite lasers in
      KTiOPO(4) . An operating wavelength range of 67 nm, from 587 to 654 nm, is
      obtained. Second-harmonic energy of almost 1 mJ is achieved at a peak wavelength
      of 620 nm. A measured factor-of-34 enhancement in acceptance angle is obtained
      with broadband harmonic generation. Frequency doubling is optimized with respect
      to the Cr:forsterite pump and laser parameters.

PMID- 18073885
TI  - Laser-diode-pumped phosphosilicate-fiber Raman laser with an output power of 1 W
      at 1.48 mum.
AB  - An all-fiber 1.48-mum generator based on a laser-diode-pumped Yb-doped double
      clad laser and a cascaded Raman wavelength converter has been developed. Second
      order Raman Stokes radiation was generated in a phosphosilicate-fiber resonator
      formed by two pairs of Bragg gratings. A slope efficiency of the Raman converter
      of 48% with respect to the power emitted by the double-clad Yb laser has been
      achieved. We obtained an output power of 1 W at a slope efficiency of 34% with
      respect to the laser-diode array power, with a total optical-to-optical
      efficiency of 23%.

PMID- 18073886
TI  - Experiments on chaos synchronization in two separate microchip lasers.
AB  - Synchronization of chaos generated in two Nd:YVO(4) microchip lasers is
      experimentally demonstrated with master-slave coupling schemes. For
      synchronization of chaos, precise locking of the sustained relaxation-oscillation
      frequency is required, as is optical frequency locking. One needs to match both
      the pump-modulation parameters for chaos generation and the laser parameters of
      the two lasers to generate perfectly synchronized chaotic spectra in the master
      slave type I coupling scheme.

PMID- 18073887
TI  - Spatial distribution of the intensity noise of a vertical-cavity surface-emitting
      semiconductor laser.
AB  - We studied anticorrelated quantum fluctuations between the TEM(00) and the
      TEM(01) transverse modes of a vertical-cavity surface-emitting semiconductor
      laser by measuring the transverse spatial distribution of the laser beam
      intensity noise. Our experimental results are found to be in good agreement with
      the predictions of a phenomenological model that accounts for quantum
      correlations between transverse modes in a light beam.

PMID- 18073888
TI  - Quasi-phase-matched difference-frequency generation in periodically poled
      Ti:LiNbO(3) channel waveguides.
AB  - Mid-infrared radiation near 2.8 mum was generated by difference-frequency
      generation in an 80-mm-long periodically poled Ti:LiNbO(3) channel waveguide by
      pump radiation near 1.55 mum (tunable external-cavity laser) and a signal
      radiation of 3.391 mum (HeNe laser). We obtained a normalized conversion
      efficiency of 105% W(-1) , which is to our knowledge the highest value ever
      reported.

PMID- 18073889
TI  - Vortex streets in walking parametric wave mixing.
AB  - The combined effects of diffraction and Poynting vector walk-off in second
      harmonic generation with pump beams that contain screw phase dislocations is
      addressed for what is believed to be the first time. We predict the spontaneous
      nucleation of multiple vortex twins whose subsequent explosion can yield quasi
      aligned patterns of single-charge vortices.

PMID- 18073890
TI  - 90 degrees phase-matched third-harmonic generation of CO(2) laser frequencies in
      AgGa(1-x)In(x)Se(2).
AB  - AgGa(1-x) In(x)Se(2) with x=0.474 was found to be 90 degrees phase matchable for
      third-harmonic generation of CO(2) laser wavelengths 9.2714-10.5910 mum by means
      of temperature tuning. Sellmeier equations and the thermo-optic constant for this
      crystal are presented.

PMID- 18073891
TI  - Determination of interferometer phase distributions by use of wavelets.
AB  - A new technique for directly extracting phase gradients from two-dimensional (2
      D) interferometer fringe data is presented. One finds the gradients by tracking
      the maximum modulus of the continuous wavelet transform of the fringe data and
      the phase distribution that is obtained, with a small error, by integration.
      Problems associated with phase unwrapping are thereby avoided. The technique is
      compared with standard methods, and excellent agreement is found. In common with
      Fourier-transform methods, the technique is capable of extracting the full 2-D
      phase distribution from a single image.

PMID- 18073892
TI  - Persistent light-induced absorption in oxidized iron-doped barium titanate
      crystals.
AB  - Illumination of oxidized iron-doped BaTiO(3) crystals with visible or ultraviolet
      light yields absorption changes of as much as 1300 m(-1) that are stable at room
      temperature. These photochromic effects cannot be erased by light, but heating
      the crystal to a moderate temperature (100 degrees C) can switch it back to its
      initial state. These effects, in particular the optical irreversibility, might be
      of interest, e.g., for optical control of charge-transport properties and for
      persistent data storage.

PMID- 18073893
TI  - Optically encoded second-harmonic generation in germanosilicate glass by a
      femtosecond laser.
AB  - Second-harmonic generation in germanosilicate glasses was encoded by coherent
      superposition of the 810-nm fundamental and the 405-nm second-harmonic light of a
      femtosecond laser. The difference spectra between the absorption spectra of the
      glasses before and after preparation were measured. An evident correlation
      between the induced second-order nonlinearity and the creation of a Ge electron
      center was observed, suggesting that a band-to-band transition by multiphoton
      absorption is probably responsible for the photoinduced second-harmonic
      generation.

PMID- 18073894
TI  - Nanostructuring with spatially localized femtosecond laser pulses.
AB  - Spatially localized femtosecond pulses have been produced by a combination of
      scanning near-field optical microscopy with ultrashort pulse lasers. With these
      pulses direct ablative writing on metal surfaces is demonstrated. Possible
      applications of this technique for nanostructuring, repair, and production of
      lithographic masks are discussed.

PMID- 18073895
TI  - Directly diode-pumped millijoule subpicosecond Yb:glass regenerative amplifier.
AB  - An Yb:glass regenerative amplifier directly side pumped by four 20-W diodes is
      demonstrated. By use of a novel pumping scheme and introduction of cylindrical
      optics into the cavity, a free-running average output power as great as 4 W with
      a TEM(00) -like mode was achieved from the bare cavity, with a 0.56 pump duty
      cycle. When the regenerative amplifier injected, 1-mJ 200-fs FWHM pulses were
      obtained following compression by use of 2-ms pump pulses and up to a 150-Hz
      repetition rate.

PMID- 18073896
TI  - Sub-two-cycle pulses from a Kerr-lens mode-locked Ti:sapphire laser: addenda.

PMID- 18073897
TI  - Determination of the optimum absorption coefficient in Cr(4+)*forsterite lasers
      under thermal loading: errata.

PMID- 18073898
TI  - Time-domain Fresnel-to-Fraunhofer diffraction with photon echoes.
AB  - A photon echo experiment in Tm(3+):YAG is reported that shows, for the first time
      to the authors' knowledge, the time-domain equivalent of the transition from near
      to far-field diffraction, including Talbot self-imaging effects. The experiment
      demonstrates the huge dispersion capability of photon echoes and opens the way to
      further exploration of space-time duality.

PMID- 18073899
TI  - High-precision frequency-domain measurements of the optical properties of turbid
      media.
AB  - We report high-precision measurements of the absorption and the reduced
      scattering coefficients for turbid media. Using a frequency-domain measurement
      technique for a point-source infinite-medium geometry, we find that the standard
      deviations of multiple measurements of the absorption coefficient mu(a) and the
      reduced scattering coefficient mu(s)(?) are less than 0.6%, and three
      independently derived values for mu(a) and mu(s)(?) agree to better than 1%.
      Measurements of mu(a) agree with measurements of a nonscattering medium to within
      1.2%. To obtain high precision requires attention to proper conditions for the
      spherical photon-density wave model, the detection linearity, and the ratio of
      the absorption rate to the source modulation rate. Frequency-domain amplitude and
      phase measurements deviate from fitted curves by 0.1% and 0.06 degrees rms,
      respectively.

PMID- 18073900
TI  - Variant fractional Fourier transformer for optical pulses.
AB  - We demonstrate that it is possible to perform a fractional Fourier transform of
      an incident pulse with a continuously variable degree of fractionality, using a
      dispersive and nonlinear Kerr medium. This medium acts as a linear waveguide for
      the optical pulse if its intensity is small and if the refractive index is
      nonlinearly time-dependently modified by a simultaneously launched bright
      soliton. For optical pulses the dispersive and nonlinear medium is perfectly
      equivalent to a graded-index refractive medium for optical beams.

PMID- 18073901
TI  - Optical forces on microparticles in an evanescent laser field.
AB  - We present a theory based on an exact calculation of the radiation forces on a
      microsized particle illuminated by evanescent waves created under total internal
      reflection in a flat substrate. The influence of the proximity of this interface
      to the particle is analyzed by a numerical simulation that addresses multiple
      scattering of light between the particle and the dielectric flat surface. We thus
      give an interpretation of the experimental results of Kawata and Sugiura [Opt.
      Lett. 17, 772 (1992)] and put forward a method that is capable of predicting new
      effects.

PMID- 18073902
TI  - Autocorrelation function of the polarization-mode dispersion vector.
AB  - We derive, for what is believed to be the first time, the autocorrelation
      function (ACF) of the polarization-mode dispersion (PMD) vector, which gives
      information on the bandwidths of the principal states of polarization. We compare
      the ACF with measured data and find good agreement. Finally, we apply the derived
      ACF to calculate the average pulse broadening that is due to PMD.

PMID- 18073903
TI  - All-fiber wavemeter and Fourier-transform spectrometer.
AB  - An all-fiber Fourier-transform spectrometer is proposed and demonstrated, based
      on the diffraction of light through the side of a standard optical fiber by a UV
      induced fiber grating. The interference pattern, whose Fourier transform yields
      the optical spectrum, is formed by light diffracted from counterpropagating modes
      in the fiber. The device is simple and compact and functions as a wavemeter, a
      fiber-optic network monitor, or a tool for fabrication and testing of long fiber
      Bragg gratings.

PMID- 18073904
TI  - High-power femtosecond-pulse reshaping near the zero-dispersion wavelength of an
      optical fiber.
AB  - Nonlinear propagation of high-power femtosecond pulses close to the zero
      dispersion wavelength of a singlemode optical fiber is studied experimentally and
      numerically. The roles of four-photon mixing, stimulated Raman scattering, and
      self-steepening in this process are represented through different extensions of
      the nonlinear Schrodinger equation.

PMID- 18073905
TI  - Use of two-photon excitation for erasable-rewritable three-dimensional bit
      optical data storage in a photorefractive polymer.
AB  - We report what is believed to be the first use of a photorefractive polymer in
      erasable-rewritable three-dimensional bit optical data storage under two-photon
      excitation. We successfully demonstrate writing, erasing, and rewriting of
      multilayered information in a photorefractive polymer consisting of 2,5-dimethyl
      4-(p-nitrophenylazo)anisole, 2,4,7-trinitro-9-fluorenone, 9-ethylcarbazole, and
      poly(N-vinylcarbazole). A three-dimensional bit density of 5 Gbits/cm(3) is
      achieved by two-photon absorption under pulsed beam illumination at an infrared
      wavelength of 800 nm in the recording process. Complete erasing of the recording
      information is achieved by use of ultraviolet illumination.

PMID- 18073906
TI  - Laser ray-tracing method for optical testing.
AB  - We have developed a novel laser ray-tracing method to measure aberrations in
      optical systems. It consists of delivering narrow laser pencils (by a laser
      scanner), recording the spots that are formed on the image plane (with a CCD
      camera), and computing the position of each centroid. This approach could be
      considered an experimental (approximate) implementation of standard numerical ray
      tracing. Several tests and experiments, including a direct comparison with a
      Hartmann-Shack wave-front sensor, provided highly satisfactory results that
      confirmed the validity of the method and revealed potential advantages.

PMID- 18073907
TI  - Subdiffraction resolution in far-field fluorescence microscopy.
AB  - We overcame the resolution limit of scanning far-field fluorescence microscopy by
      disabling the fluorescence from the outer part of the focal spot. Whereas a near
      UV pulse generates a diffraction-limited distribution of excited molecules, a
      spatially offset pulse quenches the excited molecules from the outer part of the
      focus through stimulated emission. This results in a subdiffraction-sized
      effective point-spread function. For a 1.4 aperture and a 388-nm excitation
      wavelength spatial resolution is increased from 150 +/- 8 nm to 106 +/- 8 nm with
      a single offset beam. Superior lateral resolution is demonstrated by separation
      of adjacent Pyridine 2 nanocrystals that are otherwise indiscernible.

PMID- 18073908
TI  - High-power Nd:YAG laser picosecond pulse delivery by a polymer-coated silver
      hollow-glass waveguide.
AB  - An oscillator-amplifier high-power Nd:YAG laser system was used for transmission
      of a single 50-ps-long pulse or a train of pulses through a cyclic olefin polymer
      coated silver hollow-glass waveguide. The maximum energy that was transmitted was
      150 mJ for the train of pulses and 40 mJ for the single pulse, from which
      followed a delivered power of 100 GW/cm(2) . The characteristics that were
      obtained make these waveguides promising for the delivery of high-power laser
      pulses in medical as well as other applications.

PMID- 18073909
TI  - Cr(2+):ZnSe and Co(2+):ZnSe saturable-absorber Q switches for 1.54-mum Er:glass
      lasers.
AB  - Passive Q switching of Er:glass lasers has been demonstrated with Cr(2+):ZnSe and
      Co(2+):ZnSe saturable absorbers. A pulse duration of ~50ns and an output pulse
      energy of 5 mJ were obtained with both Co:ZnSe and Cr:ZnSe passive shutters. A Q
      switched conversion efficiency of as much as 26% was obtained for Cr:ZnSe.
      Theoretical modeling exhibits satisfactory agreement with experimental data.

PMID- 18073910
TI  - Suppression of parasitic lasing in large-aperture Ti:sapphire laser amplifiers.
AB  - Transverse, parasitic lasing has been observed in several large Ti:sapphire disk
      amplifiers. It severely limits the signal gain and the pulse energy that can be
      extracted from the amplifier. We have developed a technique for suppressing these
      parasitic lasing modes based on index matching the crystal edges with an
      absorbing doped polymer thermoplastic. The parasitics are completely suppressed
      for the range of aperture sizes and pump fluences studied here. A comparison of
      the amplifier performance before and after edge cladding is presented for several
      Ti:sapphire crystals.

PMID- 18073911
TI  - Continuous-wave room-temperature laser oscillation of Cr(3+):MgO.
AB  - Continuous-wave laser oscillation of Cr(3+):MgO at room temperature was realized
      under argon-ion laser pumping at 476 and 514 nm. The free-running laser
      wavelength was 840 nm, and with different mirror sets laser oscillation at 824,
      830, 870, and 878 nm was also realized. With different crystals a maximum output
      power of 48 mW and a lowest threshold with respect to the absorbed pump power of
      80 mW were realized. The slope efficiencies with respect to the absorbed pump
      power were as high as 2.3%. No thermal effects were observed for absorbed pump
      powers as great as 2.7 W.

PMID- 18073912
TI  - Combined scanning optical coherence and two-photon-excited fluorescence
      microscopy.
AB  - We demonstrate simultaneous imaging by optical coherence microscopy (OCM) and two
      photon-excited (TPE) fluorescence microscopy. A mode-locked Ti:sapphire laser is
      focused and scanned in three dimensions through a fixed sample, generating both
      backscattered light and fluorescence light, which are independently detected.
      Both imaging modes provide rapid en-face imaging with submicrometer resolution.
      High-power delivery into the sample yields an OCM sensitivity in excess of 130 dB
      at 100-kHz pixel rates. Simultaneous imaging of cell nuclei with OCM and TPE is
      demonstrated in live drosophila embryos.

PMID- 18073913
TI  - High-phase-conjugate reflectivity (<800%) obtained by degenerate four-wave mixing
      in a continuous-wave diode-side-pumped Nd:YVO(4) amplifier.
AB  - High-phase-conjugate reflectivities of >800% have been achieved through
      degenerate four-wave mixing in a cw diode-side-pumped Nd:YVO(4) amplifier.
      Reflectivity curves are shown as a function of input pump-beam intensity for
      three values of small-signal amplifier gain, and comparison is made with a
      numerical simulation.

PMID- 18073914
TI  - Parametric oscillator directly pumped by a 1.55-mum erbium-fiber laser.
AB  - We report what is believed to be the first demonstration of an optical parametric
      oscillator directly pumped by the 1.55-mum output of an erbium-doped fiber laser.
      The oscillator, based on periodically poled lithium niobate, produced 8-muJ idler
      output near 3.8 mum at a 500-Hz repetition rate when it was pumped with 100-muJ
      60-ns pulses at 1.55 mum . Temperature tuning of the 50-mm-long PPLN crystal gave
      signal and idler ranges of 2.55 to 2.7 mum and 3.65 to 3.96 mum , respectively,
      limited by mirror reflectivity. A signal-tuning range of 40 nm was observed for
      13.5 nm of pump tuning with a fixed grating period and temperature. The optical
      parameter oscillator could be operated at low temperature with no sign of
      photorefractive damage.

PMID- 18073915
TI  - First-order type II quasi-phase-matched UV generation in periodically poled KTP.
AB  - Type II quasi-phase matching was employed for first-order frequency doubling of a
      single-longitudinal-mode Ti:sapphire laser in periodically poled KTP with a
      domain-inverted period of 9.01 mum . In a single-pass configuration, 0.44 mW of
      UV power at 398.8 nm was generated for an input of 780 mW, corresponding to a
      normalized conversion efficiency of 0.09%W(-1) cm(-1) . The nonlinear coefficient
      d(24) = 2.82 pm/V was deduced from the measurements. The larger grating period
      for the type II quasi-phase-matched second-harmonic-generation process than for
      type I quasi-phase matching, lowers the fabrication constrains in the short
      wavelength region and increases the acceptance bandwidth.

PMID- 18073916
TI  - Light-controlled electro-optic power limiter with a Bi(12)SiO(20) crystal.
AB  - An optical power limiter is a self-actuating nonlinear optical device that
      transmits low-intensity light and blocks high-intensity light. A light-controlled
      electro-optic power limiter that uses a Bi(12)SiO(20) crystal has been
      demonstrated. The threshold light intensity is determined by the control light
      and can be set to any desired level. The response time of the light-controlled
      electro-optic power limiter is of the order of 1 ms.

PMID- 18073917
TI  - Amplitude squeezing of light by means of a phase-sensitive fiber parametric
      amplifier.
AB  - We experimentally demonstrate generation of bright sub-Poissonian light by means
      of parametric deamplification in a phase-sensitive fiber amplifier that is based
      on a balanced nonlinear Sagnac interferometer. On direct detection, the
      photocurrent noise falls below the shot-noise limit by (0.6 +/- 0.2) dB (1.4 dB
      when corrected for detection losses). To observe the noise reduction we employed
      a scheme that used two orthogonally polarized pulses to cancel the noise that
      arises from the predominantly polarized guided-acoustic-wave Brillouin scattering
      in the fiber. We also present a simplified semiclassical theory of quantum-noise
      suppression by this amplifier, which is found to be in good agreement with the
      experimental results.

PMID- 18073918
TI  - Quantum-noise measurements in high-efficiency single-pass second-harmonic
      generation with femtosecond pulses.
AB  - The quantum-noise properties of single-pass second-harmonic blue-light generation
      with femtosecond pulses have been measured. A conversion efficiency of as much as
      63.5% of second-harmonic generation at 428.8 nm was observed in a KNbO(3) crystal
      with femtosecond (130-fs) pulses with wavelengths centered at 857.6 nm. The
      quantum noise on the generated blue light was measured to be 1.0 dB (1.4 dB of
      squeezing inferred) below the shot-noise limit. The noise reduction was found to
      be sensitive to the average power and the center wavelength of the input
      fundamental pulses under the condition of strong pump depletion.

PMID- 18073919
TI  - Probing nonequilibrium electron distributions in gold by use of second-harmonic
      generation.
AB  - Second-harmonic radiation is generated at a gold surface by use of a laser pulse
      that is varied in duration from 14 to 29 fs and in intensity from 10(9) to
      10(11)W/cm(2) . At laser intensities below 10(10)W/cm(2) , the second-harmonic
      signal has the expected quadratic dependence on pump-laser intensity; however, at
      higher intensities, the dependence is supraquadratic. This difference arises
      because the leading edge of the laser pulse interacts significantly with the gold
      electrons to create a nonequilibrium, photoexcited distribution. The second
      harmonic generation process occurs before electron-electron or electron-phonon
      collisions can equilibrate the distribution and therefore serves as a probe of
      the nonequilibrium distribution.

PMID- 18073920
TI  - Measurement of the electron-density profile in a discharge-ablated capillary
      waveguide.
AB  - We present the results of time-resolved interferometric measurements of the
      electron-density profile in a discharge-ablated capillary waveguide. We observe
      the development of a pronounced axial minimum in the electron-density profile
      with a relative depth of as much as 60% of the axial electron density. Such a
      profile is suitable for channeling high-intensity laser pulses.

PMID- 18073921
TI  - Femtosecond Ti:sapphire ring laser with a 2-GHz repetition rate and its
      application in time-resolved spectroscopy.
AB  - A Kerr-lens mode-locked femtosecond Ti:sapphire laser operating at a repetition
      rate of 2 GHz is demonstrated. A mirror-dispersion-controlled unidirectional ring
      cavity delivers nearly bandwidth-limited pulses of 23-fs length. Mode locking is
      self-starting without a hard aperture in the cavity. The advantages of this high
      repetition-rate oscillator in optical time-resolved spectroscopy are
      demonstrated.

PMID- 18073922
TI  - Observation of nanometer-scale optical property discrimination by use of a near
      field scanning apertureless microscope.
AB  - We examine fundamental issues related to discriminating structural and optical
      features in near-field scanning apertureless microscopy. We report a series of
      controlled experiments with nanosphere-sized standard spheres in which we
      observed significant differences in resolution and structure between an atomic
      force microscope image and a simultaneously acquired near-field optical (NFO)
      image. Further, in experiments that employed a mix of dyed and undyed nanospheres
      we found that we can observe differences in the same NFO image for adjacent
      nanospheres. Therefore we conclude that near-field scanning apertureless
      microscopy not only meets the criteria for a NFO image but also is capable of
      measuring optical properties below the diffraction limit. The two-point
      resolution was at least 200 nm when we were detecting optical phase and 50 nm
      when we were detecting optical intensity. The edge response was typically 15 nm,
      and the minimum observable features were of the order of 3 nm.

PMID- 18073923
TI  - Measuring the power-law exponent of an atmospheric turbulence phase power
      spectrum with a Shack Hartmann wave-front sensor.
AB  - For non-Kolmogorov turbulence we develop a differential angle-of-arrival
      fluctuation coefficient, which is the ratio between the transverse and
      longitudinal differential angle-of-arrival variances, and a slope structure
      correlation coefficient, which is the ratio between the transverse and
      longitudinal differences of the slope correlation function and the slope
      structure function, to measure the power-law exponent of a phase power spectrum
      with a Shack-Hartmann wave-front sensor: The differential arrival-of-angle
      fluctuation coefficient and the slope structure-correlation coefficient are both
      related to power-law exponent beta and are independent of strength parameter
      rho(0) of the turbulence. We compare the methods developed and use them to
      evaluate beta in recently completed horizontal atmospheric experiments for 1000-m
      laser beam propagation.

PMID- 18073924
TI  - Plasmon polariton modes guided by a metal film of finite width.
AB  - The properties of purely bound plasmon-polariton modes guided by a symmetric thin
      metal film of finite width are described for what is believed to be the first
      time, and a suitable mode nomenclature for identifying them is proposed. The
      dispersion characteristics of the modes as a function of film thickness are
      presented. It has been found that long-range plasmon-polariton modes exist in a
      symmetric film structure and that one of them may be suitable for optical signal
      transmission.

PMID- 18073925
TI  - Arm cavity resonant sideband control for laser interferometric gravitational wave
      detectors.
AB  - We present a new optical control scheme for a laser interferometric gravitational
      wave detector that has a high degree of tolerance to interferometer spatial
      distortions and noise on the input light. The scheme involves resonating the rf
      sidebands in an interferometer arm cavity.

PMID- 18073926
TI  - Measurement of the wavelength dependence of beam divergence for photonic crystal
      fiber.
AB  - We report measurements of the wavelength dependence of beam divergence for single
      mode photonic crystal fiber. These measurements confirm predictions of strongly
      wavelength-dependent beam divergence, consistent with the effective-index model
      for the photonic crystal cladding material.

PMID- 18073927
TI  - Measuring the group delay of fiber Bragg gratings by use of end-reflection
      interference.
AB  - A new, simple method for characterization of fiber Bragg gratings is proposed.
      The group delay of the grating is obtained from measurement of the spectral
      reflectivity response of a grating that is interfering with a bare-fiber end
      reflection.

PMID- 18073928
TI  - Enhanced photosensitivity in germanosilicate fibers exposed to CO2 laser
      radiation.
AB  - We report a novel method to increase the UV photosensitivity of GeO(2): SiO(2)
      optical fibers based on exposure to CO(2) laser irradiation before grating
      writing. Fibers treated with a CO(2) laser can produce gratings with refractive
      index modulation two times greater and a Bragg wavelength that can be 2 nm longer
      than those of untreated fibers. Experiments on GeO(2): SiO(2) preform samples
      treated with a CO(2) laser in a way similar to the fibers showed a marked
      increase of the 242-nm absorption band, which is associated with an increase of
      germanium oxygen-deficient centers and is believed to be responsible for the
      higher photorefractive response.

PMID- 18073929
TI  - Optical multilayer detection array for fast ultrasonic field mapping.
AB  - An optical multilayer detection array for ultrasonic measurements is presented.
      The probe comprises a dielectric interference filter structure that is evaporated
      onto a glass plate. An incident acoustic pressure signal deforms the layer
      system, and the induced modulation of the optical reflectance is determined by a
      simple optical detection scheme. The principle of measurement is demonstrated by
      a line scan through the focus of a broadband transducer and can be applied to
      rapid two-dimensional characterization of ultrasonic fields. The high temporal
      and spatial resolution of the measurements is combined with high sensitivity and
      durability of the probe, and, in contrast with fiber-tip multilayer hydrophones,
      the multilayer detection array provides signals that are not influenced by
      acoustic resonances and diffraction phenomena.

PMID- 18073930
TI  - Stabilization of actively mode-locked Er-doped fiber lasers in the rational
      harmonic frequency-doubling mode-locking regime.
AB  - Stabilization of an actively mode-locked fiber laser in the frequency-doubling
      rational-harmonic mode-locking regime is demonstrated experimentally for the
      first time to the authors' knowledge. The stabilization is achieved by a method
      based on minimization of the average optical power at the second output of a dual
      output Mach-Zehnder modulator used as a mode locker. This method produces long
      term stable operation of the laser with ~35-dB suppression of the pulse-to-pulse
      amplitude fluctuation caused by rational-harmonic frequency doubling.

PMID- 18073931
TI  - High-power diode-pumped Q-switched intracavity frequency-doubled Nd:YVO4 laser
      with a sandwich-type resonator.
AB  - A compact and efficient diode-pumped acousto-optically Q -switched intracavity
      frequency-doubled Nd:Y VO(4)/KTP green laser is demonstrated. With 0.5-at. % Nd:Y
      VO(4), greater than 4.6 W of 532-nm average power at a repetition rate of 50 kHz
      was generated with 17-W pump power, corresponding to a conversion efficiency of
      27%. At 10-30 kHz the pulse width is shorter than 10 ns, and the peak power is
      higher than 13 kW.

PMID- 18073932
TI  - Temporal criterion for single-frequency operation of passively Q-switched lasers.
AB  - An analytical expression for the difference in buildup time between two
      longitudinal modes in a passively Q -switched laser resonator is developed and
      compared with experimental laser data. The results support the following temporal
      criterion for single-frequency, passively Q -switched operation: The difference
      in buildup time between any two longitudinal modes of the laser resonator should
      be comparable with or greater than the laser pulse duration to ensure single
      frequency operation.

PMID- 18073933
TI  - Programmable frequency reference for subkilohertz laser stabilization by use of
      persistent spectral hole burning.
AB  - We report what is believed to be the first demonstration of laser frequency
      stabilization directly to persistent spectral holes in a solid-state material.
      The frequency reference material was deuterated CaF(2): Tm(3+) prepared with 25
      MHz-wide persistent spectral holes on the H(6)(3)?H(4)(3) transition at 798 nm.
      The beat frequency between two lasers that were independently locked to
      persistent spectral holes in separate crystal samples showed typical root Allan
      variances of 780+/-120Hz for 20-50-ms integration times.

PMID- 18073934
TI  - Laser cooling of a solid by 65K starting from room temperature.
AB  - In vacuo laser cooling of a solid from 301 to 236 K has been demonstrated. The
      sample consists of a cladded, multimode optical fiber fabricated from the
      fluorozirconate glass ZBLANP; the fiber's waveguiding core is doped with 1 wt. %
      Yb(3+) ions. Cooling of the host glass results from anti-Stokes fluorescence of
      Yb(3+) following optical pumping in the long-wavelength tail of the ion's
      absorption spectrum (lambda=1015nm) . Measurement of the time constant for
      equilibration of the sample temperature is in excellent agreement with an
      analytic calculation of this quantity.

PMID- 18073935
TI  - Comparison of polarized-light propagation in biological tissue and phantoms.
AB  - We demonstrate significant differences in the propagation of polarized light
      through biological tissue compared with two common tissue phantoms.
      Depolarization of linearly and circularly polarized light was measured versus
      propagation distance by use of two independent measurement techniques. The
      measurements were performed on adipose and myocardial tissues and on tissue
      phantoms that consisted of polystyrene microsphere suspensions and Intralipid.
      The results indicate that, in contrast with results obtained in tissue phantoms,
      linearly polarized light survives through longer propagation distances than
      circularly polarized light in biological tissue.

PMID- 18073936
TI  - Two-dimensional time-resolved direct imaging through thick biological tissues: a
      new step toward noninvasive medical imaging.
AB  - We report an original two-dimensional time-resolved direct imaging method for
      transillumination optical tomography that combines the time-gating and forward
      phase-conjugation properties of type II degenerate parametric amplification. An
      object with subcentimeter resolution embedded in 4-cm-thick chicken breast tissue
      was imaged with a signal-to-noise ratio of 2.

PMID- 18073937
TI  - Imager that combines near-infrared diffusive light and ultrasound.
AB  - We introduce an imaging technique that combines complementary features of
      ultrasound and near-infrared diffusive light imaging. We achieve the combined
      technology experimentally by mounting an ultrasound array together with multiple
      laser source and optical detector fibers upon a hand-held probe. The technique is
      demonstrated with tissue phantoms wherein both acoustic and optical sensors image
      the volume underneath the probe. Coregistration of acoustic and optical images is
      achieved with an accuracy of 0.27+/-0.20cm, approximately half of the image pixel
      size of our prototype. Accurate determination of target optical absorption is
      also achieved by use of image segmentation on the ultrasound reconstruction. The
      combined technique may provide improved breast-cancer detection sensitivity and
      specificity.

PMID- 18073938
TI  - Noncollinear second-harmonic generation in periodically poled KTiOPO4 excited by
      the Bessel beam.
AB  - Frequency doubling in periodically poled KTiOPO(4) excited by the Bessel-like
      distribution of the fundamental radiation has been investigated. Theoretical
      analysis and experiments show that the use of noncollinear geometry provides new
      possibilities for engineering nonlinear interactions in periodically poled
      crystals. We demonstrate conversion of the ring-shaped fundamental mode to the
      axial second-harmonic beam with 30% efficiency for 220-muJ Q -switched Nd:YAG
      pulses.

PMID- 18073939
TI  - Interaction of cavity solitons in degenerate optical parametric oscillators.
AB  - Numerical studies, together with asymptotic and spectral analysis, establish
      regimes in which soliton pairs in degenerate optical parametric oscillators fuse,
      repel, or form bound states. A novel bound state that is stabilized by coupled
      internal oscillations is predicted.

PMID- 18073940
TI  - Measurement of the vector character of electric fields by optical second-harmonic
      generation.
AB  - We present a scheme for the determination of the vector nature of an electric
      field by optical second-harmonic generation. We demonstrate the technique by
      mapping the two-dimensional electric-field vector of a biased transmission line
      structure on silicon with a spatial resolution of ~10mum .

PMID- 18073941
TI  - Fast optical recording in dye-doped liquid crystals.
AB  - Light-induced director reorientation in dye-doped nematic liquid crystals was
      recently reported to be an efficient method of writing permanent holographic
      gratings with high sensitivity [Phys. Rev. Lett. 82, 1855 (1999)]. We report the
      achievement of stable director reorientation in the same materials by means of a
      single 4-ns pulse of the second harmonic of a Nd:YAG laser. Fast recording of
      high-resolution holographic gratings (more than 500 lines/mm) can be obtained
      with an energy density as low as 7x10(-3)J /cm(2) .

PMID- 18073942
TI  - Difference-frequency terahertz-wave generation from 4-dimethylamino-N-methyl-4
      stilbazolium-tosylate by use of an electronically tuned Ti:sapphire laser.
AB  - Among nonlinear materials, the organic ionic salt crystal 4-dimethylamino- N 
      methyl-4-stilbazolium-tosylate (DAST) is known for its large nonlinearity. We
      generated a coherent terahertz (THz) wave, using DAST, from the difference
      frequency between two oscillating wavelengths of an electronically tuned
      Ti:sapphire laser. In LiNbO(3), LiTaO(3), KTiOPO(4), and GaP crystals, THz-wave
      generation was not observed under the same experimental conditions. This result
      proves the high efficiency of DAST crystals for generation of difference
      frequency THz waves.

PMID- 18073943
TI  - Dynamic Franz-Keldysh effect: excitonic versus free-carrier excitation schemes.
AB  - We theoretically investigate the dynamic Franz-Keldysh effect for subpicosecond
      optical pulses on quantum wells as a function of detuning from the bandgap. For
      specific spectral excitation regimes we find dramatic nonlinear enhancement
      effects that are due to the preferential creation of terahertz- (THz-) field
      driven propagating excitons and free electron-hole pairs in the THz and the
      optical domains, respectively. Our results explain why previous measurements of
      THz sidebands in the optical domain were so weak; we suggest and demonstrate a
      remarkably better experiment.

PMID- 18073944
TI  - Simultaneous femtosecond-pulse compression and second-harmonic generation in
      aperiodically poled KTiOPO(4).
AB  - We report both extracavity and intracavity simultaneous second-harmonic
      generation and compression of pulses at 1.25 mum from a synchronously pumped
      RbTiOAsO(4) -based optical parametric oscillator, using an aperiodically poled
      crystal of KTiOPO(4) . The 290-fs input pulses were temporally compressed to 120
      fs, with average output powers as great as 120 mW. The experimental results are
      compared with a numerical model that uses data obtained by characterization of
      the input pulses by use of the frequency-resolved optical gating technique.

PMID- 18073945
TI  - Nonlinearly limited saturable-absorber mode locking of an erbium fiber laser.
AB  - We describe an erbium fiber laser that is passively mode locked by a novel,
      precision antireflection-coated semiconductor saturable-absorber mirror that
      incorporates an additional two-photon absorber. It is shown that passive mode
      locking evolves from a Q-switching instability. The results are achieved by use
      of saturable absorbers that provide a large (15%) nonlinear (saturable) loss.
      Exploiting two-photon absorption can substantially reduce the peak power of the Q
      switched pulses, which results in improved reliability of the laser. Moreover,
      two-photon absorption can be used to produce an optimal stability range for
      saturable-absorber mode locking.

PMID- 18073946
TI  - Adiabatic shaping of quadratic solitons: errata.

PMID- 18073947
TI  - Clarifying the concepts of wave propagation through intermittent media.
AB  - A unified exposition of the concepts of wave propagation through an intermittent
      atmosphere is set forth. By use of the simple example of the mutual coherence
      function, consistent definitions with experimental ramifications are introduced.
      I show that (a) the long-range limit of propagation through intermittency
      involves an effective medium that is distinct from the nonintermittent
      propagation case, (b) there is no evidence that coherence always improves in the
      presence of intermittency, and (c) the estimation procedures of the parameters of
      turbulence by the current algorithms should be changed.

PMID- 18073948
TI  - Vision through semireflecting media: polarization analysis.
AB  - We present an approach to recovering scenes deteriorated by reflections off a
      semi-reflecting medium. The approach is based on imaging through a polarizer at
      two different orientations. We analyze the image-formation process, taking into
      account changes in reflection and polarization properties owing to internal
      reflections within the medium. Reconstruction by inverting this process requires
      estimation of the incidence angle (the inclination of the transparent medium). We
      estimate this angle by seeking the value that leads to decorrelation of the
      estimated scenes that are automatically and uniquely labeled reflected
      transmitted.

PMID- 18073949
TI  - Transverse load sensing by use of pi-phase-shifted fiber Bragg gratings.
AB  - The birefringence of a pi -phase-shifted fiber Bragg grating can be determined
      with high accuracy by measurement of the polarization-induced spectral splitting
      of its narrow central transmission window. The use of this feature for sensing of
      a load applied in the direction transverse to the optical fiber is demonstrated.
      A distributed force resolution of 1.4x10(-3) N/mm was obtained, which corresponds
      to a difference in the principal strains of the fiber core of 0.5mu? . We also
      show that the transverse load response of the sensor is insensitive to
      temperature.

PMID- 18073950
TI  - Dense periodic fibers with ultralow four-wave mixing over a broad wavelength
      range.
AB  - Four-wave mixing in dense periodic fiber is much less than in conventional
      dispersion management and constant-dispersion systems over a wide wavelength
      range, including the resonant wavelength.

PMID- 18073951
TI  - Frequency-division-multiplexed polarimetric fiber laser current-sensor array.
AB  - We demonstrate a novel frequency-domain-multiplexing technique for implementing
      polarimetric fiber laser current sensors. Each sensor operates at a different
      polarization-mode beat frequency that is modulated in response to applied
      electric current. A bank of bandpass filters can be used to separate signals from
      different sensors. A simple frequency-demodulation technique based on a phase
      locked loop is used for signal processing.

PMID- 18073952
TI  - Soliton wavelength-division multiplexing system with channel-isolating notch
      filters.
AB  - We propose a wavelength-division multiplexing system in which transmission of
      solitons is stabilized by fixed- or sliding-frequency notch filters (a soliton
      rail), providing channel isolation. We demonstrate analytically and numerically
      that a soliton trapped in a channel between two notches is very robust. We also
      predict an optimum ratio between the channel separation and the soliton's
      spectral width. The effects of interchannel collisions are considered, and it is
      demonstrated that these effects can be largely eliminated by notch filters, which
      require a compensatory gain that is comparable with the basic gain balancing the
      fiber loss.

PMID- 18073953
TI  - Measurement of the nonlinear optical response of optical fiber materials by use
      of spectrally resolved two-beam coupling.
AB  - We present measurements of the femtosecond nonlinear response of fiber waveguide
      materials, obtained with spectrally resolved two-beam coupling. This simple but
      sensitive technique provides all the parameters that characterize the third-order
      nonlinear optical response, including the dynamics. Measurements are made with
      nanojoule-energy pulses from a mode-locked Ti:sapphire laser and a few
      millimeters of waveguide preform, without the need for drawing fiber.

PMID- 18073954
TI  - Optical low-coherence reflectometry characterization of cladding modes excited by
      long-period fiber gratings.
AB  - The group refractive-index difference of cladding modes excited by a long-period
      fiber grating is characterized by use of the technique of optical low-coherence
      reflectometry, with a precision of <10(-4) . Very good agreement between
      theoretical and experimental results is demonstrated.

PMID- 18073955
TI  - Lock-in holography using optically addressed multiple-quantum-well spatial light
      modulators.
AB  - Perpendicular-field multiple-quantum-well optically addressed spatial light
      modulators have a response that saturates at high writing intensity. This limits
      the diffraction efficiency of low-fringe-visibility holograms. This effect is
      suppressed by use of the ability of these structures to subtract images rapidly.
      The modulator is exposed to a hologram with a spatially uniform beam, which is
      incoherent with the hologram, superimposed on top of it. Pulsing the hologram
      synchronously with the device drive voltage but leaving the uniform beam constant
      in time can build up the diffraction to large values even when the fringe
      visibility is low.

PMID- 18073956
TI  - Polarization Sagnac interferometer with postmodulation for gravitational-wave
      detection.
AB  - We describe a polarization Sagnac interferometer with an in-loop half-wave plate
      that allows signal detection at the reciprocal port of the beam splitter while
      maintaining the ability to detect the signal at a dark fringe. Postmodulation and
      balanced heterodyne detection are used to recover the signal. This topology is
      simple to control because of its common-path characteristics and its collinear
      signal and local oscillator. The robustness of this scheme to amplitude and
      frequency fluctuations of the laser is demonstrated. Intraloop birefringence in
      this interferometer acts as a loss, reducing the power on the detector. The
      magnitude of this loss is discussed and experimentally verified.

PMID- 18073957
TI  - Generation of millijoule-level soft-x-ray laser pulses at a 4-Hz repetition rate
      in a highly saturated tabletop capillary discharge amplifier.
AB  - Laser pulses with energies of as much as 1 mJ were generated at a wavelength of
      46.9 nm by single-pass amplification in a 34.5 cm-long Ne-like Ar capillary
      discharge plasma. The large gain-length product of this plasma column allows for
      soft-x-ray amplification in a highly saturated regime, resulting in efficient
      energy extraction. Average laser output pulse energy of 0.88 mJ and peak power of
      0.6 MW were obtained at a repetition rate of 4 Hz. With an estimated peak
      spectral brightness of approximately 1x10(23)photons /(s mm(2)mrad> (2)0.01%
      bandwidth) this tabletop laser is one of the brightest soft-x-ray sources to
      date.

PMID- 18073958
TI  - Selecting optical patterns with spatial phase modulation.
AB  - Optical pattern selection by use of spatial phase modulation is investigated
      experimentally in a photorefractive feedback system. A feedback mirror with
      spatially periodic phase modulation is used for selection of different spatial
      patterns. Local phase modulation is used to create patterns with coexisting
      spatial symmetries. The experimental results are consistent with numerical
      simulations based on a model with a cubicly nonlinear medium.

PMID- 18073959
TI  - Mechanisms of polarization switching in single-transverse-mode vertical-cavity
      surface-emitting lasers: thermal shift and nonlinear semiconductor dynamics.
AB  - We analyze polarization switching in vertical-cavity surface-emitting lasers,
      taking into account a proper semiconductor frequency-dependent complex
      susceptibility and spin-flip processes. Thermal effects are included as a varying
      detuning, and gain differences arise from birefringence splitting. We find that,
      for large birefringence, gain differences between the two linearly polarized
      modes are preponderant, and switching occurs owing to thermal shift. For small
      birefringence polarization switching from the high- to the low-gain mode occurs
      owing to the combined effect of birefringence and semiconductor phase-amplitude
      coupled dynamics for a finite value of the carrier spin-flip rate.

PMID- 18073960
TI  - Laser beam combining and cleanup by stimulated Brillouin scattering in a
      multimode optical fiber.
AB  - A new technique for combining low-power laser beams has been demonstrated by use
      of semiconductor diode lasers. The technique, which is appropriate for any single
      longitudinal-mode laser, is based on stimulated Brillouin scattering (SBS) in
      long multimode optical fibers. It produces a clean Gaussian-like beam that
      corresponds to the fundamental fiber mode, irrespective of the profile of the
      pump. Coherent as well as incoherent combining was demonstrated, and conversion
      slope efficiencies as high as 67% and 83% were shown to be achievable for the
      single-pass and ring-cavity SBS geometries, respectively.

PMID- 18073961
TI  - Intracavity frequency doubling of a diode-pumped external-cavity surface-emitting
      semiconductor laser.
AB  - We present a compact, robust, solid-state blue-light (490-nm) source capable of
      greater than 5 mW of output in a TEM(00) mode. This device is an optically
      pumped, vertical external-cavity surface-emitting laser with an intracavity
      frequency-doubling crystal.

PMID- 18073962
TI  - Diode-pumped nonresonant continuous-wave Raman laser in H2 with resonant optical
      feedback stabilization.
AB  - We demonstrate a nonresonant cw Raman laser pumped by an optically locked diode
      laser at 790 nm that produces cw Stokes (1178-nm) and coherent anti-Stokes (595
      nm) emission. Considering the modest pump powers, relative low cost, and
      predicted spectral purity, we expect that frequency downconversion of tunable
      diode lasers through stimulated Raman scattering will provide an attractive
      source for remote sensing, spectroscopic, and atomic physics applications. The
      Stokes laser threshold is 240+/-19muW pump power, and emission is observed over a
      roughly 10-nm range by adjustment of the optical locking feedback phase. Photon
      conversion efficiency rises throughout the pump-power region, with a peak value
      of 15+/-2% .

PMID- 18073963
TI  - Diode-pumped 1.7-W erbium 3-mum fiber laser.
AB  - We report what is to our knowledge the first 3-mu;m fiber laser of the 1-W class.
      1.7 W of output power and 17.3% slope efficiency (with respect to the launched
      pump power) at a wavelength of 2.71mum are demonstrated from a double-clad erbium
      doped ZBLAN fiber diode pumped at 790 nm. Energy transfer from the Er(3+) lower
      laser level to a Pr(3+) codopant decreases ground-state bleaching and excited
      state absorption, thus avoiding output-power saturation. This result represents
      more than an order-of-magnitude improvement over previous work of which we are
      aware. Advantages over current crystal-laser designs include nearly transverse
      fundamental-mode operation, reduced thermal effects, and ease of use, e.g., in
      medical endoscopy.

PMID- 18073964
TI  - Composition dependence of the photoinduced refractive-index change in lead
      silicate glasses.
AB  - A large photoinduced refractive-index change (as great as Dn=0.21+/-0.04) is
      obtained in lead silicate glasses by irradiation with the frequency-quadrupled
      output of a Q -switched YAG laser (266 nm). An approximately exponential
      relationship is found between the photoinduced refractive-index change and the
      lead cation mole fraction over the composition range from 18.7% to 57%. The
      induced refractive-index change is permanent and shows no decay after heating to
      360 degrees C during 1 h. Dispersion of the refractive-index change suggests that
      the photosensitivity is associated with changes in the intrinsic glass absorption
      edge.

PMID- 18073965
TI  - Cavityless oscillation through backward quasi-phase-matched second-harmonic
      generation.
AB  - In an amplifier, nonlinear feedback from mismatched backward second-harmonic
      generation leads to strong enhancement of parametric conversion. With reference
      to LiNbO(3) quasi-phase-matched waveguides, we propose a parametric bistable
      device that operates simultaneously in two colors and in the cw or the self
      pulsed regime.

PMID- 18073966
TI  - Singly resonant continuous-wave optical parametric oscillator pumped by a diode
      laser.
AB  - We report on what is believed to be the first singly resonant cw optical
      parametric oscillator (SRO) that is directly pumped by a diode laser. The SRO
      consists of a 38-mm-long periodically poled LiNbO(3) crystal in a four-mirror
      signal-resonant ring cavity. Pumped by 2.5 W of 925-nm diode-laser radiation, the
      SRO generates 480 mW of single-frequency idler radiation at 2.1mum . The
      wavelengths of the signal and the idler output are tuned in the ranges of 1.55 to
      1.70mum and 2.03 to 2.29mum, respectively, by tuning the wavelength of the diode
      laser from 924.0 to 925.4 nm.

PMID- 18073967
TI  - Second-harmonic generation in waveguides induced by photorefractive spatial
      solitons.
AB  - We demonstrate experimentally second-harmonic generation in waveguides induced by
      photorefractive solitons and show that the conversion efficiency is improved
      considerably. These induced waveguides are flexible and can be generated in any
      crystalline direction that allows soliton formation, and thus offer broad
      tunability (by rotation of the crystal), which cannot exist in fabricated
      waveguides.

PMID- 18073968
TI  - Generation of ultraviolet (335-nm) light by intracavity frequency doubling from
      active mode-locking action of an external-cavity AlGaInP diode laser.
AB  - An intracavity frequency-doubling scheme was merged with an actively mode-locked
      AlGaInP laser diode with an external cavity to provide efficient generation of
      335-nm ultraviolet light. Intense pulses of <16ps were successfully generated
      inside the cavity at subgigahertz repetition frequencies. We applied those pulses
      to intracavity second-harmonic generation from a 5-mm-long LiIO(3) crystal, which
      resulted in average ultraviolet power of 70muW for an average fundamental power
      of 73 mW.

PMID- 18073969
TI  - Near-field probing of nanoscale nonlinear optical processes.
AB  - We report a study of two nonlinear optical processes at the nanoscale level,
      using a near-field probe: (i) two-photon-pumped upconversion from ZnS:Mn
      nanoparticles encapsulated with 2-[{(?) -2-[4 -(ethylsulfonyl) phenyl]- 1
      ethenyl} (methyl)anilino]- 1-ethanethiol and (ii) second-harmonic generation
      (SHG) from N -(4-nitrophenyl)- (L) -prolinol crystallites. The use of highly
      efficient nonlinear organic chromophores together with special processing on the
      nanometer scale made it possible to observe and characterize what are believed to
      be the smallest topographically distinguishable objects reported so far, using
      nonlinear optical techniques. Issues pertaining to the study of two-photon
      excited emission and SHG by use of a near-field probe are discussed.

PMID- 18073970
TI  - Periodically poled potassium niobate for second-harmonic generation at 463 nm.
AB  - We report on the fabrication and characterization of quasi-phase-matched
      potassium niobate crystals for second-harmonic generation. Periodic 30-mum -pitch
      antiparallel ferroelectric domains are fabricated by means of poling in an
      electrical field. Both birefrigence and periodic phase shift of the generated
      second harmonic contribute to phase matching when the d(31) nonlinear optical
      tensor element is used. 3.8 mW of second-harmonic radiation at 463 nm is
      generated by frequency doubling of the output of master-oscillator power
      amplifier diode laser in a 5-mm-long crystal. The measured effective nonlinear
      coefficient is 3.7pm/V. The measured spectral acceptance bandwidth of 0.25 nm
      corresponds to the theoretical value.

PMID- 18073971
TI  - Multiple-channel wavelength conversion by use of engineered quasi-phase-matching
      structures in LiNbO(3) waveguides.
AB  - We report difference frequency generation-based wavelength converters with
      multiple phase-matching wavelengths that use engineered quasi-phase-matching
      structures in LiNbO(3) waveguides. Multiple-channel wavelength conversion is
      demonstrated within the 1.5-mum band and between the 1.3- and 1.5-mum bands. With
      simultaneous use of M pump wavelengths, these devices can also be used to perform
      wavelength broadcasting, in which each of N input signals is converted into M
      output wavelengths.

PMID- 18073972
TI  - Waveguides formed by incoherent dark solitons.
AB  - We demonstrate experimentally optical guidance of coherent light beams, using
      incoherent light. Such guidance is made possible by generation of partially
      spatially incoherent self-trapped dark beams (dark incoherent solitons) in a
      noninstantaneous nonlinear medium. In the one-dimensional case, the incoherent
      solitons induce single and Y-junction planar waveguides, whereas in the two
      dimensional case, they form circular waveguides. These experiments introduce the
      possibility of controlling high-power laser beams with low-power incoherent light
      sources such as LED's or lightbulbs.

PMID- 18073973
TI  - Critical slowing down of space-charge field relaxation in photorefractive
      sillenites.
AB  - We propose a theoretical model for the recently reported anomalously long decay
      of a space-charge field that was resonantly excited in a photorefractive
      sillenite crystal [Phys. Rev. Lett. 79, 67 (1997)]. The model is based on the
      conventional concept of charge transfer and does not require excessively large
      values of the quality factor for space-charge waves. The effect in question is
      qualified as a critical slowing of the relaxation process as the threshold of
      optical oscillation is approached.

PMID- 18073974
TI  - Parameter optimization for a reflective bistable twisted nematic display by use
      of the Poincar spheree method.
AB  - Although reflective bistable twisted nematic (RBTN) displays have potential in
      low-power-consumption applications, to achieve the optimum conditions for both
      bistable states simultaneously remains a challenge. We use a geometrical method
      based on the Poincare sphere representation to obtain the optimum conditions that
      can simultaneously satisfy both bistable states for a RBTN structure. With this
      method, the optimum conditions can be obtained analytically and the operation
      modes can be clearly visualized and better understood.

PMID- 18073975
TI  - 40-Gbits transmission in dispersion-management links with step-index fiber and
      linear compensation.
AB  - The dynamic behavior of single-channel transmission in standard fibers with
      strong dispersion management and linear compensating devices was theoretically
      and numerically analyzed. We compared a single pulse and a pseudorandom sequence
      to highlight the relevant roles played by nonlinearity-induced spectrum
      distortion and pulse interaction. As a result, 40/Gbit/s transmission on an 1800
      km dispersion-management link with 100-km spans of standard fiber was obtained.

PMID- 18073976
TI  - High-quality sub-100-fs optical pulse generation by fiber-optic soliton
      compression of gain-switched distributed-feedback laser-diode pulses in
      conjunction with nonlinear optical fiber loops.
AB  - We report our investigations of a new and simpler femtosecond fiber-optic soliton
      compressor for chirp-compensated gain-switched diode-laser pulses and of pedestal
      suppression by a compound fiber loop mirror (CFLM) and nonlinear-optical loop
      mirrors (NOLM's), both of which are designed for sub-100-fs pulse generation of
      high quality. The soliton compressor, composed of a 21.1-m-long steplike
      dispersion profiled fiber, exhibited 44-fs pulses and a compression ratio of
      approximately 60. Pedestals of 100-fs soliton pulses were suppressed successfully
      (>20 dB) by the CFLM and the NOLM's. In particular, 63-fs pedestal-free sech(2)
      pulses were obtained by NOLM propagation.

PMID- 18073977
TI  - Autocorrelation measurement of femtosecond laser pulses by use of a ZnSe two
      photon detector array.
AB  - We demonstrate autocorrelation measurements of 85-fs Ti:sapphire laser pulses,
      using a 32-pixel ZnSe detector array in a single-shot geometry. The two-photon
      photoconductor is fabricated by deposition of an array of interdigitated gold
      fingers on a single-crystal ZnSe substrate.

PMID- 18073978
TI  - Two-dimensional angular optical scattering patterns as droplets evolve into
      clusters.
AB  - Remarkable changes in the two-dimensional angular optical scattering (TAOS)
      pattern are observed when an acoustically levitated water droplet with inclusions
      evolves into a dry aggregate. The emergence of polystyrene latex sphere
      inclusions near the droplet surface has a clear effect on the TAOS. A speckle
      pattern in the TAOS replaces the continuous contours associated with Mie
      scattering from a smooth droplet. Once the contours break up, this speckle
      pattern persists as the levitated droplet evaporates, making the transition from
      a droplet with inclusions to a dried aggregate. The initial emergence of the
      speckle pattern is observed for an inclusion volume fraction near 8%.

PMID- 18073979
TI  - Optical phase-space distributions for low-coherence light.
AB  - Using a novel heterodyne technique, we measure optical phase-space distributions
      in momentum and position for low-coherence light. Quantitative information is
      obtained simultaneously about the longitudinal and the transverse coherence
      properties as well as the wave-front curvature of the light field. This method
      can be used to monitor these optical parameters directly for signal fields
      scattered from samples of interest, for tomographic imaging.

PMID- 18073980
TI  - Observation of the breakup of a prechirped N-soliton in an optical fiber.
AB  - We present what is believed to be the first experimental evidence showing the
      breakup of a chirped N-soliton pulse into an ordered train of fundamental
      solitons, as predicted by theory. We also present numerical experiments that
      confirm this phenomenon. Implications for optical communications systems that use
      chirped pulses are discussed.

PMID- 18073981
TI  - Second-harmonic generation in Langmuir Blodgett waveguide overlays on single-mode
      optical fiber.
AB  - Second-harmonic radiation has been obtained from Langmuir-Blodgett films of E-N 
      octadecyl-4-[2-(4-dibutylaminophenyl)ethenyl]quinolinium octadecylsulfate,
      deposited as a waveguide overlay upon optical fiber that is single mode at the
      pump wavelength (lambda=1064 nm) . A quadratic relationship between the pump
      power and second-harmonic intensity was observed.

PMID- 18073982
TI  - Time-domain Fourier optics for polarization-mode dispersion compensation.
AB  - We report on a novel technique to compensate for all-order polarization-mode
      dispersion. By means of this technique, based on a suitable combination of phase
      modulation and group-velocity dispersion, we compensated for as much as 60 ps of
      differential group delay that affected a 10-Gbit/s return-to-zero data stream.

PMID- 18073983
TI  - Signal masking for chaotic optical communication using external-cavity diode
      lasers.
AB  - Amplitude modulation is used to encode a message into the output of a chaotic
      laser-diode optical transmitter, and decoding of the message by use of a
      synchronized chaotic laser-diode receiver is demonstrated experimentally. The
      chaotic carrier is shown to effectively mask the transmitted message.

PMID- 18073985
TI  - Mode analysis in optics through fractional transforms.
AB  - The relationship between the mode content and the fractional Fourier and
      fractional Hankel transforms of a function is established. It is shown that the
      Laguerre-Gauss spectrum of a rotationally symmetric wave front can be determined
      from the wave front's fractional Hankel transforms taken at the optical axis.

PMID- 18073984
TI  - Toward practical holey fiber technology: fabrication, splicing, modeling, and
      characterization.
AB  - We report the fabrication of long lengths of mechanically robust holey fiber and
      what is believed to be the first demonstration of their splicing. These practical
      advances have permitted what is to our knowledge the first detailed
      characterization of a holey fiber near 1.5mum . We compare dispersion
      measurements with our numerical predictions and confirm that our model can be
      used to predict accurately holey fiber properties.

PMID- 18073986
TI  - 20-GHz broadly tunable and stable mode-locked semiconductor amplifier fiber ring
      laser.
AB  - We present an actively mode-locked fiber ring laser that uses a single active
      semiconductor optical amplifier device to provide both gain and gain modulation
      from an external optical pulse train. The laser source generated 4.3-ps pulses at
      20 GHz over a 16-nm tuning range and is stable against environmental changes and
      simple to build.

PMID- 18073987
TI  - Mid-infrared microlenses fabricated by the melting method.
AB  - It is shown that by using the melting method it is possible to fabricate
      microlenses that work with mid-IR radiation. The fabrication method is described,
      and the characteristics of the polymeric material and the fabricated lenses are
      shown.

PMID- 18073988
TI  - Room-temperature laser action at 4.34.4 mum in CaGa(2)S(4):Dy(3+).
AB  - We report room-temperature mid-IR laser operation in a new low-phonon-frequency
      nonhygroscopic host crystal, calcium thiogallate (CaGa(2)S(4)) . Laser action at
      4.314.38 mum on the Dy(3+)H(11/2)(6)?H(13/2)(6) transition occurred with a
      maximum slope efficiency of 1.6%.

PMID- 18073989
TI  - Suppression of low-frequency fluctuations and stabilization of a semiconductor
      laser subjected to optical feedback from a double cavity: theoretical results.
AB  - We demonstrate numerically that low-frequency fluctuations (LFF's) observed in a
      laser diode subjected to a first optical feedback with a short delay are
      suppressed by means of an adequate second optical feedback. The general idea of
      this technique is based on the observation that second feedback can suppress the
      antimodes that are responsible for the crises in the LFF regime. Furthermore, we
      observe that the second optical feedback can steer an unstable laser that is
      biased near threshold into a stable regime.

PMID- 18073990
TI  - In vivo ultrahigh-resolution optical coherence tomography.
AB  - Ultrahigh-resolution optical coherence tomography (OCT) by use of state of the
      art broad-bandwidth femtosecond laser technology is demonstrated and applied to
      in vivo subcellular imaging. Imaging is performed with a Kerr-lens mode-locked
      Ti:sapphire laser with double-chirped mirrors that emits sub-two-cycle pulses
      with bandwidths of up to 350 nm, centered at 800 nm. Longitudinal resolutions of
      ~1mum and transverse resolution of 3mum, with a 110-dB dynamic range, are
      achieved in biological tissue. To overcome depth-of-field limitations we perform
      zone focusing and image fusion to construct a tomogram with high transverse
      resolution throughout the image depth. To our knowledge this is the highest
      longitudinal resolution demonstrated to date for in vivo OCT imaging.

PMID- 18073991
TI  - Nonlinear optical catastrophe from a smooth initial beam.
AB  - We observed an optical cusp diffraction catastrophe with an initially smooth but
      elongated Gaussian beam with an aspect ratio of 2:1. Nonlinear and linear
      diffraction regimes account for the near-field elliptical annulus and the far
      field spatially complex astroid.

PMID- 18073992
TI  - Periodically poled lithium niobate monolithic nanosecond optical parametric
      oscillators and generators.
AB  - We fabricated and characterized periodically poled lithium niobate monolithic
      optical parametric oscillators (OPO's) and generators. The compact monolithic
      devices were trivial to align and operate and provided widely tunable, nearly
      diffraction-limited, stable output pulses. Low thresholds and high conversion
      efficiencies were obtained when the devices were pumped with 3.5-ns 1.064-mum
      pulses. In addition, the monolithic OPO devices exhibited broad tuning by crystal
      rotation through noncollinear phase matching. The bandwidth-broadening effects
      exhibited in the noncollinear phase-matching geometry were measured and
      explained.

PMID- 18073993
TI  - Attaining 186-nm light generation in cooled beta-BaB(2)O(4) crystal.
AB  - The transparency range of beta-BaB(2)O(4) (BBO) was expanded by means of cooling,
      and the resulting absorption coefficient at 193.4 nm was reduced to 0.29cm(-1) at
      91 K from 1.39cm(-1) at 295 K. Further, generation of light at 186.0 nm (the
      measurement limit in air) by type I sum-frequency generation (SFG) based on
      fundamental (744-nm) and third-harmonic (248-nm) light from a Ti:sapphire laser
      was confirmed for cooled BBO. Calculations based on observed data for SFG
      wavelengths and phase-matching angles indicate a potential for cooled BBO to
      generate wavelengths as low as 181.7 nm.

PMID- 18073994
TI  - Efficient nanosecond optical parametric oscillators based on periodically poled
      KTP emitting in the 1.8-2.5-mum spectral region.
AB  - The use of periodically poled KTiOPO(4) as a gain medium in efficient nanosecond
      optical parametric oscillators pumped by a flash-lamp-pumped Q-switched Nd:YAG
      laser is demonstrated. Parametric radiation in the 1.8-2.5-mu m spectral region
      was achieved when the crystal temperature was tuned from 10 to 100 degrees C. A
      maximum total output energy of 1.8 mJ was obtained at a pump level of 3.5 mJ.
      Stable operation was achieved, with conversion efficiencies reaching 50%. No gray
      tracking or laser damage was observed, even for pump intensities of 450MW/cm(2).

PMID- 18073995
TI  - Efficient quasi-phase-matched frequency doubling with phase compensation by a
      wedged crystal in a standing-wave external cavity.
AB  - In standing-wave enhancement cavities for frequency doubling, second-harmonic
      fields are generated in both directions of propagation. To add the fields
      coherently, one should compensate for the phase shifts introduced by dispersive
      elements in the cavity. We experimentally demonstrate phase compensation in a
      compact standing-wave frequency-doubling cavity by use of a wedged periodically
      poled KTP crystal. The highest conversion efficiency and second-harmonic power
      obtained by pumping with a 1064-nm cw Nd:YAG laser were 69.4% and 268 mW,
      respectively.

PMID- 18073996
TI  - Electro-optic Michelson Gires Tournois modulator for optical information
      processing and optical fiber communications.
AB  - We propose and demonstrate an electro-optic modulator based on a Michelson
      interferometer with a Gires-Tournois etalon (GTE, or asymmetric Fabry-Perot
      etalon) in one of the two arms. The insertion of a GTE significantly reduces the
      required interaction length or the operation voltage. Our experimental and
      theoretical results agree well. An extension of our setup to a waveguide
      configuration can lead to practical modulators and switches with greater
      compactness and reduced operation voltage for optical fiber communications.

PMID- 18073997
TI  - Tunable terahertz emission through multiple Rabi flopping in a dc-biased quantum
      well: a new strategy.
AB  - By exploiting the Rabi-flopping-induced coherent density oscillations in a weakly
      dc-biased quantum well, we describe a new method for producing very intense
      (roughly kilovolts per centimeter), tunable terahertz transients. We achieved
      tunability by simply varying the area of the input optical pulse.

PMID- 18073998
TI  - Terahertz pulse measurement with an optical streak camera.
AB  - Incorporating an electro-optic modulator with a conventional optical streak
      camera extends the spectral range of the streak camera from the optical region
      (UV, visible, and near-IR) to the terahertz region (far-IR and millimeter-wave)
      with a minimum modification. We demonstrate the temporal measurement of freely
      propagating terahertz pulses with single-shot capability.

PMID- 18073999
TI  - Subfemtosecond compression of periodic laser pulses.
AB  - It is shown that a recently proposed technique of molecular modulation can be
      used to compress mode-locked laser pulses into the subfemtosecond domain. The
      method relies on driving a molecular oscillation with a periodic pulse train. The
      coherent molecular motion, in turn, modulates the laser frequency and allows
      pulse compression by group-velocity dispersion of the same molecular medium.

PMID- 18074000
TI  - The 'broken heart' syndrome: What can be learned from the tears and distress?

PMID- 18074001
TI  - OX40-OX40L interactions: a promising therapeutic target for allergic diseases?
AB  - Recent advances in understanding the cellular and molecular mechanisms of atopy
      have shed light on potential targets for the development of new therapies for
      allergic diseases. In this issue of the JCI, Seshasayee et al. provide direct in
      vivo evidence that OX40 has critical roles in allergic inflammation mediated by
      thymic stromal lymphopoietin (TSLP) (see the related article beginning on page
      3868). Blockade of interactions between OX40 on Th2 cells and OX40 ligand (OX40L)
      on TSLP-activated DCs using an OX40L-specific monoclonal antibody, inhibited Th2
      cell-mediated immune responses in both mouse and nonhuman primate models of
      allergic inflammation. The results point to potential therapeutic approaches to
      targeting the cellular and molecular mechanism underlying TSLP-mediated allergic
      inflammation.

PMID- 18074002
TI  - Ethnic differences in low-density lipoprotein particle size in hypertensive
      adults.
AB  - BACKGROUND: Hypertensive African Americans have higher rates of coronary heart
      disease (CHD) than their non-Hispanic white counterparts despite having higher
      HDL cholesterol (HDL-C) levels and lower triglyceride levels. OBJECTIVE: The goal
      of the present study was to assess whether low-density lipoprotein (LDL) particle
      size, a correlate of the above lipid traits and a risk factor for CHD, differs
      between hypertensive African Americans and whites. METHODS: Participants included
      1177 hypertensive African Americans from Jackson MS (60+/-7 years, 72.4% women)
      and 860 hypertensive whites from Rochester MN (58+/-7 years, 56.7% women). LDL
      particle size was measured by polyacrylamide gradient gel electrophoresis. Within
      each sex, we assessed whether ethnicity was significantly associated with
      differences in LDL particle size after adjustment for CHD risk factors (age,
      total cholesterol, HDL-C, triglycerides, systolic BP, diabetes, history of
      smoking, body mass index), statin use, and estrogen use (in women), and
      "lifestyle" variables (physical activity and alcohol intake). RESULTS: Although
      HDL-C levels were higher and triglyceride levels lower in African Americans, LDL
      particle size (adjusted for CHD risk factors) was lower (P < 0.0001) in African
      American men and women than in their white counterparts (mean +/- SD; men,
      267.6+/-5.2 A vs. 270.2+/-4.8 A; women 268.7+/-5.1 A vs. 271.3+/-5.1 A). In both
      sexes, African American ethnicity was associated with lower LDL particle size
      after adjustment for CHD risk factors, statin use and estrogen use (in women), as
      well as physical activity and alcohol intake. CONCLUSION: Hypertensive African
      American men and women have lower LDL particle size than their white counterparts
      despite having higher HDL-C and lower triglycerides.

PMID- 18074003
TI  - Depressive symptoms, depression proneness, and outcome expectancies for cigarette
      smoking.
AB  - The high rates of cigarette smoking among depressed persons may be partially
      explained by increased positive expectancies for cigarette smoking among this
      population. In view of theoretical and empirical work on depressed people's
      negative views of the future, though, it would be expected that depressed smokers
      would hold particularly negative expectancies about the effects of cigarette
      smoking. The two current studies examined the relations between depression and
      smoking outcome expectancies in (a) a general population of adult regular smokers
      and (b) adult smokers seeking to quit smoking. Depressive symptoms and depression
      proneness both showed significant positive correlations with positive
      expectancies for cigarette smoking. Several positive correlations with negative
      expectancies also emerged. Thus, experiencing depressive symptoms may serve to
      amplify both favorable and unfavorable expectancies about the effects of smoking.

PMID- 18074005
TI  - The relation between syntactic and morphological recovery in agrammatic aphasia:
      A case study.
AB  - BACKGROUND: Production of grammatical morphology is typically impaired in
      agrammatic aphasic individuals, as is their capacity to produce the syntactic
      structure responsible for licensing that morphology. Whether these two
      impairments are causally related has been an issue of long-standing debate. If
      morphological deficits are a side-effect of underlying syntactic ones, as has
      been claimed (Friedmann & Grodzinsky, 1997; Izvorski & Ullman, 1999), therapy
      which improves the syntactic deficit should remediate the morphological deficit
      as well. This paper reports a case study of one individual with such co-occurring
      impairments and describes their recovery in response to linguistically-motivated
      treatment targeting his syntactic deficits.  METHODS #ENTITYSTARTX00026;
      PROCEDURES: MD is a 56 year-old male diagnosed with non-fluent Broca's aphasia
      subsequent to a left-hemisphere CVA, with limited capacity to produce
      syntactically complex utterances and grammatical morphology. He was enrolled in
      therapy using Treatment of Underlying Forms (TUF; Thompson & Shapiro, 2005),
      targeting production of sentences involving Wh-movement (object relative
      clauses). MD participated in twice-weekly treatment sessions for approximately
      two months, with daily probes assessing his production of treated and untreated
      sentence types. In addition, probes assessing his grammatical morphology and
      sentence production were administered pre- and post-treatment.  OUTCOMES
      #ENTITYSTARTX00026; RESULTS: Pre-treatment scores in tests of grammatical
      morphology and sentence production indicated deficits in both domains. During
      treatment, MD successfully acquired production of a variety of sentence with Wh
      movement, though this did not generalize to sentences involving a grammatically
      distinct movement operation (NP-movement). Post-treatment scores also indicated a
      lack of improvement in production of grammatical morphology.  CONCLUSIONS: The
      dissociation between MD's morphological and syntactic recovery indicates that the
      recovery of syntactic and morphological processes in aphasia may occur
      independently. This result is thus surprising under approaches in which
      morphological and syntactic impairments are strongly and causally related in
      aphasia, such as the Tree-Pruning Hypothesis (Friedmann, 2001; Friedmann &
      Grodzinsky, 1997). Further, these results reinforce the conclusion that aphasia
      treatment can lead to generalization, but only to linguistic material which is in
      a subset relation to trained structures (Thompson, Shapiro, Kiran & Sobecks,
      2003).

PMID- 18074004
TI  - 5S rRNA: Structure and Function from Head to Toe.
AB  - 5S rRNA is uniquely positioned so as to link together all of the functional
      centers of the ribosome. Previous studies have supported the hypothesis that 5S
      rRNA acts as a physical transducer of information, facilitating communication
      between the different functional centers and coordinating of the multiple events
      catalyzed by the ribosome. Here, we present a synthesis of both structural and
      genetic information to construct a more detailed picture of how 5S rRNA may act
      to transmit and coordinate all of the functional centers of the ribosome.

PMID- 18074006
TI  - The Two-Person Construction of Defenses: Disorganized Attachment Strategies,
      Unintegrated Mental States, and Hostjle/Helpless Relational Processes.

PMID- 18074007
TI  - Validation of an instrument to measure inter-organisational linkages in general
      practice.
AB  - PURPOSE: Linkages between general medical practices and external services are
      important for high quality chronic disease care. The purpose of this research is
      to describe the development, evaluation and use of a brief tool that measures the
      comprehensiveness and quality of a general practice's linkages with external
      providers for the management of patients with chronic disease. In this study,
      clinical linkages are defined as the communication, support, and referral
      arrangements between services for the care and assistance of patients with
      chronic disease. METHODS: An interview to measure surgery-level (rather than
      individual clinician-level) clinical linkages was developed, piloted, reviewed,
      and evaluated with 97 Australian general practices. Two validated survey
      instruments were posted to patients, and a survey of locally available services
      was developed and posted to participating Divisions of General Practice (support
      organisations). Hypotheses regarding internal validity, association with local
      services, and patient satisfaction were tested using factor analysis, logistic
      regression and multilevel regression models. RESULTS: The resulting General
      Practice Clinical Linkages Interview (GP-CLI) is a nine-item tool with three
      underlying factors: referral and advice linkages, shared care and care planning
      linkages, and community access and awareness linkages. Local availability of
      chronic disease services has no affect on the comprehensiveness of services with
      which practices link, however, comprehensiveness of clinical linkages has an
      association with patient assessment of access, receptionist services, and of
      continuity of care in their general practice. CONCLUSIONS: The GP-CLI may be
      useful to researchers examining comparable health care systems for measuring the
      comprehensiveness and quality of linkages at a general practice-level with
      related services, possessing both internal and external validity. The tool can be
      used with large samples exploring the impact, outcomes, and facilitators of high
      quality clinical linkages in general practice.

PMID- 18074008
TI  - Geometric triangular chiral hexagon crystal-like complexes organization in
      pathological tissues biological collision order.
AB  - The present study describes and documents self-assembly of geometric triangular
      chiral hexagon crystal like complex organizations (GTCHC) in human pathological
      tissues. The authors have found this architectural geometric expression at
      macroscopic and microscopic levels mainly in cancer processes. This study is
      based essentially on macroscopic and histopathologic analyses of 3000 surgical
      specimens: 2600 inflammatory lesions and 400 malignant tumours. Geometric
      complexes identified photographically at macroscopic level were located in the
      gross surgical specimen, and these areas were carefully dissected. Samples were
      taken to carry out histologic analysis. Based on the hypothesis of a collision
      genesis mechanism and because it is difficult to carry out an appropriate
      methodological observation in biological systems, the authors designed a model
      base on other dynamic systems to obtain indirect information in which a strong
      white flash wave light discharge, generated by an electronic device, hits over
      the lines of electrical conductance structured in helicoidal pattern. In their
      experimental model, the authors were able to reproduce and to predict polarity,
      chirality, helicoid geometry, triangular and hexagonal clusters through
      electromagnetic sequential collisions. They determined that similar events among
      constituents of extracelular matrix which drive and produce piezoelectric
      activity are responsible for the genesis of GTCHC complexes in pathological
      tissues. This research suggests that molecular crystals represented by triangular
      chiral hexagons derived from a collision-attraction event against collagen type I
      fibrils emerge at microscopic and macroscopic scales presenting a lateral
      assembly of each side of hypertrophy helicoid fibers, that represent energy flow
      in cooperative hierarchically chiral electromagnetic interaction in pathological
      tissues and arises as a geometry of the equilibrium in perturbed biological
      systems. Further interdisciplinary studies must be carried out to reproduce,
      manipulate and amplify their activity and probably use them as a base to develop
      new therapeutic strategies in cancer.

PMID- 18074009
TI  - Sexual risk behaviors for HIV/AIDS in Chuuk State, Micronesia: the case for HIV
      prevention in vulnerable remote populations.
AB  - BACKGROUND: After the first two cases of locally-acquired HIV infection were
      recognized in Chuuk State, Federated States of Micronesia (FSM), a public health
      response was initiated. The purpose of the response was to assess the need for
      HIV education and prevention services, to develop recommendations for controlling
      further spread of HIV in Chuuk, and to initiate some of the prevention measures.
      METHODOLOGY/PRINCIPAL FINDINGS: A public health team conducted a survey and rapid
      HIV testing among a sample of residents on the outer islands in Chuuk. Local
      public health officials conducted contact tracing and testing of sex partners of
      the two locally-acquired cases of HIV infection. A total of 333 persons completed
      the survey. The majority knew that HIV is transmitted through unprotected sexual
      contact (81%), injection drug use (61%), or blood transfusion (64%). Sexual
      activity in the past 12 months was reported among 159 participants, including 90
      females and 69 males. Compared to women, men were more likely to have had
      multiple sex partners, to have been drunk during sex, but less likely to have
      used a condom in the past 12 months. The two men with locally acquired HIV
      infection had unprotected anal sex with a third Chuukese man who likely
      contracted HIV while outside of Chuuk. All 370 persons who received voluntary,
      confidential HIV counseling and testing had HIV negative test results.
      CONCLUSIONS/SIGNIFICANCE: Despite the low HIV seroprevalence, risky sexual
      behaviors in this small isolated population raise concerns about the potential
      for rapid spread of HIV. The lack of knowledge about risks, along with
      stigmatizing attitudes towards persons infected with HIV and high risk sexual
      behaviors indicate the need for resources to be directed toward HIV prevention in
      Chuuk and on other Pacific Islands.

PMID- 18074010
TI  - Early detection of tuberculosis outbreaks among the San Francisco homeless: trade
      offs between spatial resolution and temporal scale.
AB  - BACKGROUND: San Francisco has the highest rate of tuberculosis (TB) in the U.S.
      with recurrent outbreaks among the homeless and marginally housed. It has been
      shown for syndromic data that when exact geographic coordinates of individual
      patients are used as the spatial base for outbreak detection, higher detection
      rates and accuracy are achieved compared to when data are aggregated into
      administrative regions such as zip codes and census tracts. We examine the effect
      of varying the spatial resolution in the TB data within the San Francisco
      homeless population on detection sensitivity, timeliness, and the amount of
      historical data needed to achieve better performance measures. METHODS AND
      FINDINGS: We apply a variation of space-time permutation scan statistic to the TB
      data in which a patient's location is either represented by its exact coordinates
      or by the centroid of its census tract. We show that the detection sensitivity
      and timeliness of the method generally improve when exact locations are used to
      identify real TB outbreaks. When outbreaks are simulated, while the detection
      timeliness is consistently improved when exact coordinates are used, the
      detection sensitivity varies depending on the size of the spatial scanning window
      and the number of tracts in which cases are simulated. Finally, we show that when
      exact locations are used, smaller amount of historical data is required for
      training the model. CONCLUSION: Systematic characterization of the spatio
      temporal distribution of TB cases can widely benefit real time surveillance and
      guide public health investigations of TB outbreaks as to what level of spatial
      resolution results in improved detection sensitivity and timeliness. Trading
      higher spatial resolution for better performance is ultimately a tradeoff between
      maintaining patient confidentiality and improving public health when sharing
      data. Understanding such tradeoffs is critical to managing the complex interplay
      between public policy and public health. This study is a step forward in this
      direction.

PMID- 18074011
TI  - Genetic impact of a severe El Nino event on Galapagos marine iguanas
      (Amblyrhynchus cristatus).
AB  - The El Nino-Southern Oscillation (ENSO) is a major source of climatic
      disturbance, impacting the dynamics of ecosystems worldwide. Recent models
      predict that human-generated rises in green-house gas levels will cause an
      increase in the strength and frequency of El Nino warming events in the next
      several decades, highlighting the need to understand the potential biological
      consequences of increased ENSO activity. Studies have focused on the ecological
      and demographic implications of El Nino in a range of organisms, but there have
      been few systematic attempts to measure the impact of these processes on genetic
      diversity in populations. Here, we evaluate whether the 1997-1998 El Nino altered
      the genetic composition of Galapagos marine iguana populations from eleven
      islands, some of which experienced mortality rates of up to 90% as a result of El
      Nino warming. Specifically, we measured the temporal variation in microsatellite
      allele frequencies and mitochondrial DNA diversity (mtDNA) in samples collected
      before (1991/1993) and after (2004) the El Nino event. Based on microsatellite
      data, only one island (Marchena) showed signatures of a genetic bottleneck, where
      the harmonic mean of the effective population size (N(e)) was estimated to be
      less than 50 individuals during the period between samplings. Substantial
      decreases in mtDNA variation between time points were observed in populations
      from just two islands (Marchena and Genovesa). Our results suggests that, for the
      majority of islands, a single, intense El Nino event did not reduce marine iguana
      populations to the point where substantial neutral genetic diversity was lost. In
      the case of Marchena, simultaneous changes to both nuclear and mitochondrial DNA
      variation may also be the result of a volcanic eruption on the island in 1991.
      Therefore, studies that seek to evaluate the genetic impact of El Nino must also
      consider the confounding or potentially synergistic effect of other environmental
      and biological forces shaping populations.

PMID- 18074012
TI  - A novel interhemispheric interaction: modulation of neuronal cooperativity in the
      visual areas.
AB  - BACKGROUND: The cortical representation of the visual field is split along the
      vertical midline, with the left and the right hemi-fields projecting to separate
      hemispheres. Connections between the visual areas of the two hemispheres are
      abundant near the representation of the visual midline. It was suggested that
      they re-establish the functional continuity of the visual field by controlling
      the dynamics of the responses in the two hemispheres. METHODS/PRINCIPAL FINDINGS:
      To understand if and how the interactions between the two hemispheres participate
      in processing visual stimuli, the synchronization of responses to identical or
      different moving gratings in the two hemi-fields were studied in anesthetized
      ferrets. The responses were recorded by multiple electrodes in the primary visual
      areas and the synchronization of local field potentials across the electrodes
      were analyzed with a recent method derived from dynamical system theory.
      Inactivating the visual areas of one hemisphere modulated the synchronization of
      the stimulus-driven activity in the other hemisphere. The modulation was stimulus
      specific and was consistent with the fine morphology of callosal axons in
      particular with the spatio-temporal pattern of activity that axonal geometry can
      generate. CONCLUSIONS/SIGNIFICANCE: These findings describe a new kind of
      interaction between the cerebral hemispheres and highlight the role of axonal
      geometry in modulating aspects of cortical dynamics responsible for stimulus
      detection and/or categorization.

PMID- 18074013
TI  - Loss of sugar detection by GLUT2 affects glucose homeostasis in mice.
AB  - BACKGROUND: Mammals must sense the amount of sugar available to them and respond
      appropriately. For many years attention has focused on intracellular glucose
      sensing derived from glucose metabolism. Here, we studied the detection of
      extracellular glucose concentrations in vivo by invalidating the transduction
      pathway downstream from the transporter-detector GLUT2 and measured the
      physiological impact of this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We produced
      mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking
      glucose-mediated gene expression in vitro without affecting glucose metabolism.
      Impairment of GLUT2-mediated sugar detection transiently protected transgenic
      mice against starvation and streptozotocin-induced diabetes, suggesting that both
      low- and high-glucose concentrations were not detected. Transgenic mice favored
      lipid oxidation, and oral glucose was slowly cleared from blood due to low
      insulin production, despite massive urinary glucose excretion. Kidney adaptation
      was characterized by a lower rate of glucose reabsorption, whereas pancreatic
      adaptation was associated with a larger number of small islets.
      CONCLUSIONS/SIGNIFICANCE: Molecular invalidation of sugar sensing in GLUT2-loop
      transgenic mice changed multiple aspects of glucose homeostasis, highlighting by
      a top-down approach, the role of membrane glucose receptors as potential
      therapeutic targets.

PMID- 18074014
TI  - Widespread epigenetic abnormalities suggest a broad DNA methylation erasure
      defect in abnormal human sperm.
AB  - BACKGROUND: Male-factor infertility is a common condition, and etiology is
      unknown for a high proportion of cases. Abnormal epigenetic programming of the
      germline is proposed as a possible mechanism compromising spermatogenesis of some
      men currently diagnosed with idiopathic infertility. During germ cell maturation
      and gametogenesis, cells of the germ line undergo extensive epigenetic
      reprogramming. This process involves widespread erasure of somatic-like patterns
      of DNA methylation followed by establishment of sex-specific patterns by de novo
      DNA methylation. Incomplete reprogramming of the male germ line could, in theory,
      result in both altered sperm DNA methylation and compromised spermatogenesis.
      METHODOLOGY/PRINCIPAL FINDING: We determined concentration, motility and
      morphology of sperm in semen samples collected by male members of couples
      attending an infertility clinic. Using MethyLight and Illumina assays we measured
      methylation of DNA isolated from purified sperm from the same samples.
      Methylation at numerous sequences was elevated in DNA from poor quality sperm.
      CONCLUSIONS: This is the first report of a broad epigenetic defect associated
      with abnormal semen parameters. Our results suggest that the underlying mechanism
      for these epigenetic changes may be improper erasure of DNA methylation during
      epigenetic reprogramming of the male germ line.

PMID- 18074015
TI  - Experience of violence and socioeconomic position in South Africa: a national
      study.
AB  - BACKGROUND: Violence is a leading cause of morbidity and mortality in South
      Africa and needs to be researched from a public health perspective. Typically in
      violence research, socioeconomic position is used in the analysis to control for
      confounding. Social epidemiology approaches this variable as a primary
      determinant of interest and is used in this research to better understand the
      aetiology of violence in South Africa. We hypothesised that measures of
      socioeconomic position (employment, education and household wealth) would be
      inversely related to violence at the individual and household levels.
      METHODOLOGY/PRINCIPAL FINDINGS: Data came from the 1998 South African Demographic
      and Health Survey (SADHS). Measures of socioeconomic position used were
      employment, education and household wealth. Eighty-eight people (0.2%) received
      treatment for a violent injury in the previous 30 days and 103 households (0.9%)
      experienced a violent death in the previous year. Risk factors for violence at
      the individual level included employment (41% of those who experienced violence
      were employed vs. 27% of those who did not, p = 0.02), and education (those who
      experienced violence had on average, one year more education than those who did
      not, p = 0.04). Belonging to a household in the wealthiest quintile was
      protective against violence (OR: 0.32; 95% CI: 0.12-0.89). In contrast, at the
      household level all three measures of socioeconomic position were protective
      against the experience of a violent death. The only association to persist in the
      multivariate analysis was that between the wealth of the household and violence
      at the individual level. CONCLUSIONS/SIGNIFICANCE: Our hypothesis was supported
      if household wealth was used as the measure of socioeconomic position at the
      individual level. While more research is needed to inform the conflicting results
      observed between the individual and household levels, this analysis has begun to
      identify the disparities across the socioeconomic structure with respect to
      violent outcomes.

PMID- 18074016
TI  - Modulation of bacterial Type III secretion system by a spermidine transporter
      dependent signaling pathway.
AB  - BACKGROUND: Many gram-negative bacterial pathogens employ Type III secretion
      systems (T3SS) to inject effector proteins into host cells in infectious
      processes. METHODOLOGY/PRINCIPAL FINDINGS: By screening a transposon mutant
      library of P. aeruginosa, we found that mutation of spuDEFGH, which encode a
      major spermidine uptake system, abolished the expression of the exsCEBA operon
      that codes for key T3SS regulators under inducing conditions (low calcium). Whole
      genome microarray analysis revealed that inactivation of the spermidine uptake
      system significantly decreased the transcriptional expression of most, if not
      all, T3SS genes. Consistently, the spermidine uptake mutants showed decreased
      expression of the T3SS genes in responding to host cell extract and attenuated
      cytotoxicity. Furthermore, exogenous addition of spermidine to the wild type
      strain PAO1 enhanced the expression of exsCEBA and also the effector protein
      genes. CONCLUSION/SIGNIFICANCE: Cumulatively, these data have depicted a novel
      spermidine transporter-dependent signaling pathway, which appears to play an
      essential role in modulation of T3SS expression in P. aeruginosa.

PMID- 18074017
TI  - Monoallelic expression of multiple genes in the CNS.
AB  - The inheritance pattern of a number of major genetic disorders suggests the
      possible involvement of genes that are expressed from one allele and silent on
      the other, but such genes are difficult to detect. Since DNA methylation in
      regulatory regions is often a mark of gene silencing, we modified existing
      microarray-based assays to detect both methylated and unmethylated DNA sequences
      in the same sample, a variation we term the MAUD assay. We probed a 65 Mb region
      of mouse Chr 7 for gene-associated sequences that show two distinct DNA
      methylation patterns in the mouse CNS. Selected genes were then tested for allele
      specific expression in clonal neural stem cell lines derived from reciprocal F(1)
      (C57BL/6xJF1) hybrid mice. In addition, using a separate approach, we directly
      analyzed allele-specific expression of a group of genes interspersed within
      clusters of OlfR genes, since the latter are subject to allelic exclusion.
      Altogether, of the 500 known genes in the chromosomal region surveyed, five show
      monoallelic expression, four identified by the MAUD assay (Agc1, p (pink-eyed
      dilution), P4ha3 and Thrsp), and one by its proximity to OlfR genes (Trim12).
      Thrsp (thyroid hormone responsive SPOT14 homolog) is expressed in hippocampus,
      but the human protein homolog, S14, has also been implicated in aggressive breast
      cancer. Monoallelic expression of the five genes is not coordinated at a
      chromosome-wide level, but rather regulated at individual loci. Taken together,
      our results suggest that at least 1% of previously untested genes are subject to
      allelic exclusion, and demonstrate a dual approach to expedite their
      identification.

PMID- 18074018
TI  - What causes partial F1 hybrid viability? Incomplete penetrance versus genetic
      variation.
AB  - BACKGROUND: Interspecific hybrid crosses often produce offspring with reduced but
      non-zero survivorship. In this paper we ask why such partial inviability occurs.
      This partial inviability could arise from incomplete penetrance of lethal
      Dobzhansky-Muller incompatibilities (DMIs) shared by all members of a hybrid
      cross. Alternatively, siblings may differ with respect to the presence or number
      of DMIs, leading to genotype-dependent variation in viability and hence non
      Mendelian segregation of parental alleles in surviving F1 hybrids.
      METHODOLOGY/PRINCIPAL FINDINGS: We used amplified fragment length polymorphisms
      (AFLPs) to test for segregation distortion in one hybrid cross between green and
      longear sunfish (Lepomis cyanellus and L. megalotis). Hybrids showed partial
      viability, and twice as much segregation distortion (36.8%) of AFLPs as an
      intraspecific control cross (18.8%). Incomplete penetrance of DMIs, which should
      cause genotype-independent mortality, is insufficient to explain the observed
      segregation distortion. CONCLUSIONS/SIGNIFICANCE: We conclude that F1 hybrid
      sunfish are polymorphic for DMIs, either due to sex-linked DMI loci (causing
      Haldane's Rule), or polymorphic autosomal DMI loci. Because few AFLP markers were
      sex-linked (2%), the most parsimonious conclusion is that parents may have been
      heterozygous for loci causing hybrid inviability.

PMID- 18074019
TI  - Does time really slow down during a frightening event?
AB  - Observers commonly report that time seems to have moved in slow motion during a
      life-threatening event. It is unknown whether this is a function of increased
      time resolution during the event, or instead an illusion of remembering an
      emotionally salient event. Using a hand-held device to measure speed of visual
      perception, participants experienced free fall for 31 m before landing safely in
      a net. We found no evidence of increased temporal resolution, in apparent
      conflict with the fact that participants retrospectively estimated their own fall
      to last 36% longer than others' falls. The duration dilation during a frightening
      event, and the lack of concomitant increase in temporal resolution, indicate that
      subjective time is not a single entity that speeds or slows, but instead is
      composed of separable subcomponents. Our findings suggest that time-slowing is a
      function of recollection, not perception: a richer encoding of memory may cause a
      salient event to appear, retrospectively, as though it lasted longer.

PMID- 18074020
TI  - Global patterns in seasonal activity of influenza A/H3N2, A/H1N1, and B from 1997
      to 2005: viral coexistence and latitudinal gradients.
AB  - Despite a mass of research on the epidemiology of seasonal influenza, overall
      patterns of infection have not been fully described on broad geographic scales
      and for specific types and subtypes of the influenza virus. Here we provide a
      descriptive analysis of laboratory-confirmed influenza surveillance data by type
      and subtype (A/H3N2, A/H1N1, and B) for 19 temperate countries in the Northern
      and Southern hemispheres from 1997 to 2005, compiled from a public database
      maintained by WHO (FluNet). Key findings include patterns of large scale co
      occurrence of influenza type A and B, interhemispheric synchrony for subtype
      A/H3N2, and latitudinal gradients in epidemic timing for type A. These findings
      highlight the need for more countries to conduct year-round viral surveillance
      and report reliable incidence data at the type and subtype level, especially in
      the Tropics.

PMID- 18074022
TI  - High resolution population maps for low income nations: combining land cover and
      census in East Africa.
AB  - BACKGROUND: Between 2005 and 2050, the human population is forecast to grow by
      2.7 billion, with the vast majority of this growth occurring in low income
      countries. This growth is likely to have significant social, economic and
      environmental impacts, and make the achievement of international development
      goals more difficult. The measurement, monitoring and potential mitigation of
      these impacts require high resolution, contemporary data on human population
      distributions. In low income countries, however, where the changes will be
      concentrated, the least information on the distribution of population exists. In
      this paper we investigate whether satellite imagery in combination with land
      cover information and census data can be used to create inexpensive, high
      resolution and easily-updatable settlement and population distribution maps over
      large areas. METHODOLOGY/PRINCIPAL FINDINGS: We examine various approaches for
      the production of maps of the East African region (Kenya, Uganda, Burundi, Rwanda
      and Tanzania) and where fine resolution census data exists, test the accuracies
      of map production approaches and existing population distribution products. The
      results show that combining high resolution census, settlement and land cover
      information is important in producing accurate population distribution maps.
      CONCLUSIONS: We find that this semi-automated population distribution mapping at
      unprecedented spatial resolution produces more accurate results than existing
      products and can be undertaken for as little as $0.01 per km(2). The resulting
      population maps are a product of the Malaria Atlas Project (MAP:
      http://www.map.ox.ac.uk) and are freely available.

PMID- 18074021
TI  - Human RECQ1 is a DNA damage responsive protein required for genotoxic stress
      resistance and suppression of sister chromatid exchanges.
AB  - BACKGROUND: DNA helicases are ubiquitous enzymes that unwind DNA in an ATP
      dependent and directionally specific manner. Unwinding of double-stranded DNA is
      essential for the processes of DNA repair, recombination, transcription, and DNA
      replication. Five human DNA helicases sharing sequence similarity with the E.
      coli RecQ helicase have been identified. Three of the human RecQ helicases are
      implicated in hereditary diseases (Bloom syndrome, Werner syndrome, and Rothmund
      Thomson syndrome) which display clinical symptoms of premature aging and cancer.
      RECQ1 helicase is the most highly expressed of the human RecQ helicases; however,
      a genetic disease has yet not been linked to mutations in the RECQ1 gene, and the
      biological functions of human RECQ1 in cellular DNA metabolism are not known.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we report that RECQ1 becomes
      phosphorylated upon DNA damage and forms irradiation-induced nuclear foci that
      associate with chromatin in human cells. Depletion of RECQ1 renders human cells
      sensitive to DNA damage induced by ionizing radiation or the topoisomerase
      inhibitor camptothecin, and results in spontaneous gamma-H2AX foci and elevated
      sister chromatid exchanges, indicating aberrant repair of DNA breaks. Consistent
      with a role in homologous recombinational repair, endogenous RECQ1 is associated
      with the strand exchange protein Rad51 and the two proteins directly interact
      with high affinity. CONCLUSION/SIGNIFICANCE: Collectively, these results provide
      the first evidence for a role of human RECQ1 in the response to DNA damage and
      chromosomal stability maintenance and point to the vital importance of RECQ1 in
      genome homeostasis.

PMID- 18074023
TI  - Increased litterfall in tropical forests boosts the transfer of soil CO2 to the
      atmosphere.
AB  - Aboveground litter production in forests is likely to increase as a consequence
      of elevated atmospheric carbon dioxide (CO(2)) concentrations, rising
      temperatures, and shifting rainfall patterns. As litterfall represents a major
      flux of carbon from vegetation to soil, changes in litter inputs are likely to
      have wide-reaching consequences for soil carbon dynamics. Such disturbances to
      the carbon balance may be particularly important in the tropics because tropical
      forests store almost 30% of the global soil carbon, making them a critical
      component of the global carbon cycle; nevertheless, the effects of increasing
      aboveground litter production on belowground carbon dynamics are poorly
      understood. We used long-term, large-scale monthly litter removal and addition
      treatments in a lowland tropical forest to assess the consequences of increased
      litterfall on belowground CO(2) production. Over the second to the fifth year of
      treatments, litter addition increased soil respiration more than litter removal
      decreased it; soil respiration was on average 20% lower in the litter removal and
      43% higher in the litter addition treatment compared to the controls but litter
      addition did not change microbial biomass. We predicted a 9% increase in soil
      respiration in the litter addition plots, based on the 20% decrease in the litter
      removal plots and an 11% reduction due to lower fine root biomass in the litter
      addition plots. The 43% measured increase in soil respiration was therefore 34%
      higher than predicted and it is possible that this 'extra' CO(2) was a result of
      priming effects, i.e. stimulation of the decomposition of older soil organic
      matter by the addition of fresh organic matter. Our results show that increases
      in aboveground litter production as a result of global change have the potential
      to cause considerable losses of soil carbon to the atmosphere in tropical
      forests.

PMID- 18074025
TI  - Revisiting estimates of CTL killing rates in vivo.
AB  - Recent experimental advances have allowed the estimation of the in vivo rates of
      killing of infected target cells by cytotoxic T lymphocytes (CTL). We present
      several refinements to a method applied previously to quantify killing of targets
      in the spleen using a dynamical model. We reanalyse data previously used to
      estimate killing rates of CTL specific for two epitopes of lymphocytic
      choriomeningitis virus (LCMV) in mice and show that, contrary to previous
      estimates the "killing rate" of effector CTL is approximately twice that of
      memory CTL. Further, our method allows the fits to be visualized, and reveals one
      potentially interesting discrepancy between fits and data. We discuss extensions
      to the basic CTL killing model to explain this discrepancy and propose
      experimental tests to distinguish between them.

PMID- 18074024
TI  - Recombinant interleukin-24 lacks apoptosis-inducing properties in melanoma cells.
AB  - IL-24, also known as melanoma differentiation antigen 7 (mda-7), is a member of
      the IL-10 family of cytokines and is mainly produced by Th(2) cells as well as by
      activated monocytes. Binding of IL-24 to either of its two possible heterodimeric
      receptors IL-20R1/IL-20R2 and IL-22R/IL-20R2 activates STAT3 and/or STAT1 in
      target tissues such as lung, testis, ovary, keratinocytes and skin. To date, the
      physiological properties of IL-24 are still not well understood but available
      data suggest that IL-24 affects epidermal functions by increasing proliferation
      of dermal cells. In stark contrast to its "normal" and physiological behaviour,
      IL-24 has been reported to selectively and efficiently kill a vast variety of
      cancer cells, especially melanoma cells, independent of receptor expression and
      Jak-STAT signalling. These intriguing properties have led to the development of
      adenovirally-expressed IL-24, which is currently being evaluated in clinical
      trials. Using three different methods, we have analysed a large panel of melanoma
      cell lines with respect to IL-24 and IL-24 receptor expression and found that
      none of the investigated cell lines expressed sufficient amounts of functional
      receptor pairs and therefore did not react to IL-24 stimulation with Jak/STAT
      activation. Results for three cell lines contrasted with previous studies, which
      reported presence of IL-24 receptors and activation of STAT3 following IL-24
      stimulation. Furthermore, evaluating four different sources and modes of IL-24
      administration (commercial recombinant IL-24, bacterially expressed GST-IL-24
      fusion protein, IL-24 produced from transfected Hek cells, transiently over
      expressed IL-24) no induction or increase in cell death was detected when
      compared to appropriate control treatments. Thus, we conclude that the cytokine
      IL-24 itself has no cancer-specific apoptosis-inducing properties in melanoma
      cells.

PMID- 18074026
TI  - Cross-attraction between an exotic and a native pine bark beetle: a novel
      invasion mechanism?
AB  - BACKGROUND: Aside from the ecological impacts, invasive species fascinate
      ecologists because of the unique opportunities that invasives offer in the study
      of community ecology. Some hypotheses have been proposed to illustrate the
      mechanisms that allow exotics to become invasive. However, positive interactions
      between exotic and native insects are rarely utilized to explain invasiveness of
      pests. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present information on a recently
      formed association between a native and an exotic bark beetle on their shared
      host, Pinus tabuliformis, in China. In field examinations, we found that 35-40%
      of P. tabuliformis attacked by an exotic bark beetle, Dendroctonus valens, were
      also attacked by a native pine bark beetle, Hylastes parallelus. In the
      laboratory, we found that the antennal and walking responses of H. parallelus to
      host- and beetle-produced compounds were similar to those of the exotic D. valens
      in China. In addition, D. valens was attracted to volatiles produced by the
      native H. parallelus. CONCLUSIONS/SIGNIFICANCE: We report, for the first time,
      facilitation between an exotic and a native bark beetle seems to involve overlap
      in the use of host attractants and pheromones, which is cross-attraction. The
      concept of this interspecific facilitation could be explored as a novel invasive
      mechanism which helps explain invasiveness of not only exotic bark beetles but
      also other introduced pests in principle. The results reported here also have
      particularly important implications for risk assessments and management
      strategies for invasive species.

PMID- 18074027
TI  - Clustered gene expression changes flank targeted gene loci in knockout mice.
AB  - BACKGROUND: Gene expression profiling using microarrays is a powerful technology
      widely used to study regulatory networks. Profiling of mRNA levels in mutant
      organisms has the potential to identify genes regulated by the mutated protein.
      METHODOLOGY/PRINCIPLE FINDINGS: Using tissues from multiple lines of knockout
      mice we have examined genome-wide changes in gene expression. We report that a
      significant proportion of changed genes were found near the targeted gene.
      CONCLUSIONS/SIGNIFICANCE: The apparent clustering of these genes was explained by
      the presence of flanking DNA from the parental ES cell. We provide
      recommendations for the analysis and reporting of microarray data from knockout
      mice.

PMID- 18074028
TI  - Scrapie-specific pathology of sheep lymphoid tissues.
AB  - Transmissible spongiform encephalopathies (TSEs) or prion diseases often result
      in accumulation of disease-associated PrP (PrP(d)) in the lymphoreticular system
      (LRS), specifically in association with follicular dendritic cells (FDCs) and
      tingible body macrophages (TBMs) of secondary follicles. We studied the effects
      of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and
      electron microscopy. FDCs of sheep were grouped according to morphology as
      immature, mature or regressing. Scrapie was associated with FDC dendrite
      hypertrophy and electron dense deposit or vesicles. PrP(d) was located using
      immunogold labelling at the plasmalemma of FDC dendrites and, infrequently,
      mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were
      identified as immunoglobulins suggesting that excess immune complexes are
      retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph
      nodes, macrophages outside the follicle and a proportion of germinal centre TBMs
      accumulated PrP(d) within endosomes and lysosomes. In addition, TBMs showed
      PrP(d) in association with the cell membrane, non-coated pits and vesicles, and
      also with discrete, large and random endoplasmic reticulum networks, which co
      localised with ubiquitin. These observations suggest that PrP(d) is internalised
      via the caveolin-mediated pathway, and causes an abnormal disease-related
      alteration in endoplasmic reticulum structure. In contrast to current dogma, this
      study shows that sheep scrapie is associated with cytopathology of germinal
      centres, which we attribute to abnormal antigen complex trapping by FDCs and
      abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs
      and TBMs differs from those of scrapie infected neurones and glial cells
      suggesting that different PrP(d)/cell membrane interactions occur in different
      cell types.

PMID- 18074029
TI  - A randomized, crossover study to evaluate the pharmacokinetics of amantadine and
      oseltamivir administered alone and in combination.
AB  - The threat of potential pandemic influenza requires a reevaluation of licensed
      therapies for the prophylaxis or treatment of avian H5N1 infection that may adapt
      to man. Among the therapies considered for use in pandemic influenza is the co
      administration of ion channel and neuraminidase inhibitors, both to potentially
      increase efficacy as well as to decrease the emergence of resistant isolates. To
      better understand the potential for drug interactions, a cross-over, randomized,
      open-label trial was conducted with amantadine, 100 mg po bid, and oseltamivir,
      75 mg po bid, given alone or in combination for 5 days. Each subject (N = 17)
      served as their own control and was administered each drug alone or in
      combination, with appropriate wash-out. Co-administration with oseltamivir had no
      clinically significant effect on the pharmacokinetics (PK) of amantadine [mean
      ratios (90% CI) for AUC(0-12) 0.93 (0.89, 0.98) and C(max) 0.96 (0.90, 1.02)].
      Similarly, amantadine co-administration did not affect oseltamivir PK [AUC(0-12)
      0.92 (0.86, 0.99) and C(max) 0.85 (0.73, 0.99)] or the PK of the metabolite,
      oseltamivir carboxylate [AUC(0-12) 0.98 (0.95, 1.02) and C(max) 0.95 (0.89,
      1.01)]. In this small trial there was no evidence of an increase in adverse
      events. Although many more subjects would need to be studied to rule out a
      synergistic increase in adverse events, the combination in this small human drug
      drug interaction trial appears safe and without pharmacokinetic consequences.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00416962.

PMID- 18074030
TI  - Detection of chromosomal structural alterations in single cells by SNP arrays: a
      systematic survey of amplification bias and optimized workflow.
AB  - BACKGROUND: In single-cell human genome analysis using whole-genome amplified
      product, a strong amplification bias involving allele dropout and preferential
      amplification hampers the quality of results. Using an oligonucleotide single
      nucleotide polymorphism (SNP) array, we systematically examined the nature of
      this amplification bias, including frequency, degree, and preference for genomic
      location, and we assessed the effects of this amplification bias on subsequent
      genotype and chromosomal copy number analyses. METHODOLOGY/PRINCIPAL FINDINGS: We
      found a large variability in amplification bias among the amplified products
      obtained by multiple displacement amplification (MDA), and this bias had a severe
      effect on the genotype and chromosomal copy number analyses. We established
      optimal experimental conditions for pre-screening for high-quality amplified
      products, processing array data, and analyzing chromosomal structural
      alterations. Using this optimized protocol, we successfully detected previously
      unidentified chromosomal structural alterations in single cells from a
      lymphoblastoid cell line. These alterations were subsequently confirmed by
      karyotype analysis. In addition, we successfully obtained reproducible
      chromosomal copy number profiles of single cells from the cell line with a
      complex karyotype, indicating the applicability and potential of our optimized
      workflow. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the quality of
      amplification products should be critically assessed before using them for
      genomic analyses. The method of MDA-based whole-genome amplification followed by
      SNP array analysis described here will be useful for exploring chromosomal
      alterations in single cells.

PMID- 18074031
TI  - Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal
      integrity.
AB  - BACKGROUND: Probiotics are proposed to positively modulate the intestinal
      epithelial barrier formed by intestinal epithelial cells (IECs) and intercellular
      junctions. Disruption of this border alters paracellular permeability and is a
      key mechanism for the development of enteric infections and inflammatory bowel
      diseases (IBDs). METHODOLOGY AND PRINCIPAL FINDINGS: To study the in vivo effect
      of probiotic Escherichia coli Nissle 1917 (EcN) on the stabilization of the
      intestinal barrier under healthy conditions, germfree mice were colonized with
      EcN or K12 E. coli strain MG1655. IECs were isolated and analyzed for gene and
      protein expression of the tight junction molecules ZO-1 and ZO-2. Then, in order
      to analyze beneficial effects of EcN under inflammatory conditions, the probiotic
      was orally administered to BALB/c mice with acute dextran sodium sulfate (DSS)
      induced colitis. Colonization of gnotobiotic mice with EcN resulted in an up
      regulation of ZO-1 in IECs at both mRNA and protein levels. EcN administration to
      DSS-treated mice reduced the loss of body weight and colon shortening. In
      addition, infiltration of the colon with leukocytes was ameliorated in EcN
      inoculated mice. Acute DSS colitis did not result in an anion secretory defect,
      but abrogated the sodium absorptive function of the mucosa. Additionally,
      intestinal barrier function was severely affected as evidenced by a strong
      increase in the mucosal uptake of Evans blue in vivo. Concomitant administration
      of EcN to DSS treated animals resulted in a significant protection against
      intestinal barrier dysfunction and IECs isolated from these mice exhibited a more
      pronounced expression of ZO-1. CONCLUSION AND SIGNIFICANCE: This study
      convincingly demonstrates that probiotic EcN is able to mediate up-regulation of
      ZO-1 expression in murine IECs and confer protection from the DSS colitis
      associated increase in mucosal permeability to luminal substances.

PMID- 18074032
TI  - Impact of resistant starch on body fat patterning and central appetite
      regulation.
AB  - BACKGROUND: Adipose tissue patterning has a major influence on the risk of
      developing chronic disease. Environmental influences on both body fat patterning
      and appetite regulation are not fully understood. This study was performed to
      investigate the impact of resistant starch (RS) on adipose tissue deposition and
      central regulation of appetite in mice. METHODOLOGY AND PRINCIPLE FINDINGS: Forty
      mice were randomised to a diet supplemented with either the high resistant starch
      (HRS), or the readily digestible starch (LRS). Using (1)H magnetic resonance (MR)
      methods, whole body adiposity, intrahepatocellular lipids (IHCL) and
      intramyocellular lipids (IMCL) were measured. Manganese-enhanced MRI (MEMRI) was
      used to investigate neuronal activity in hypothalamic regions involved in
      appetite control when fed ad libitum. At the end of the interventional period,
      adipocytes were isolated from epididymal adipose tissue and fasting plasma
      collected for hormonal and adipokine measurement. Mice on the HRS and LRS diet
      had similar body weights although total body adiposity, subcutaneous and visceral
      fat, IHCL, plasma leptin, plasma adiponectin plasma insulin/glucose ratios was
      significantly greater in the latter group. Adipocytes isolated from the LRS group
      were significantly larger and had lower insulin-stimulated glucose uptake. MEMRI
      data obtained from the ventromedial and paraventricular hypothalamic nuclei
      suggests a satiating effect of the HRS diet despite a lower energy intake.
      CONCLUSION AND SIGNIFICANCE: Dietary RS significantly impacts on adipose tissue
      patterning, adipocyte morphology and metabolism, glucose and insulin metabolism,
      as well as affecting appetite regulation, supported by changes in neuronal
      activity in hypothalamic appetite regulation centres which are suggestive of
      satiation.

PMID- 18074033
TI  - Exchanging murine and human immunoglobulin constant chains affects the kinetics
      and thermodynamics of antigen binding and chimeric antibody autoreactivity.
AB  - Mouse-human chimeric antibodies composed of murine variable (V) and human (C)
      chains are useful therapeutic reagents. Consequently, we investigated whether
      heterologous C-regions from mice and humans affected specificity and affinity,
      and determined the contribution of C(H) glycosylation to antigen binding. The
      interaction of a 12-mer peptide mimetic with monoclonal antibody (mAb) 18B7 to
      Cryptococcus neoformans glucuronoxylomannan, and its chimeric (ch) and
      deglycosylated forms were studied by surface plasmon resonance. The equilibrium
      and rate association constants for the chAb were higher than for mAb 18B7. V
      region affinity was not affected by C(H) region glycosylation whereas
      heterologous C region of the same isotype altered the Ab binding affinity and the
      specificity for self-antigens. Structural models displayed local differences that
      implied changes on the connectivity of residues. These findings suggest that V
      region conformational changes can be dictated by the C(H) domains through an
      allosteric effect involving networks of highly connected amino acids.

PMID- 18074034
TI  - A randomized open-label trial of artesunate- sulfadoxine-pyrimethamine with or
      without primaquine for elimination of sub-microscopic P. falciparum parasitaemia
      and gametocyte carriage in eastern Sudan.
AB  - BACKGROUND: In areas of seasonal malaria transmission, treatment of asymptomatic
      carriers of malaria parasites, whose parasitaemia persists at low densities
      throughout the dry season, could be a useful strategy for malaria control. We
      carried out a randomized trial to compare two drug regimens for clearance of
      parasitaemia in order to identify the optimum regimen for use in mass drug
      administration in the dry season. METHODOLOGY AND PRINCIPAL FINDINGS: A two-arm
      open-label randomized controlled trial was conducted during the dry season in an
      area of distinct seasonal malaria in two villages in Gedarif State in eastern
      Sudan. Participants were asymptomatic adults and children aged over 6 months,
      with low-density P. falciparum infection detected by PCR. Participants were
      randomized to receive artesunate/sulfadoxine-pyrimethamine (AS+SP) combination
      for three days with or without a dose of primaquine (PQ) on the fourth day.
      Parasitaemia detected by PCR on days 3, 7 and 14 after the start of treatment and
      gametocytes detected by RT-PCR on days 7 and 14 were then recorded. 104
      individuals who had low density parasitaemia at screening were randomized and
      treated during the dry season. On day 7, 8.3% were positive by PCR in the
      AS+SP+PQ group and 6.5% in the AS+SP group (risk difference 1.8%, 95%CI -10.3% to
      +13.8%). At enrolment, 12% (12/100) were carrying gametocytes. This was reduced
      to 6.4% and 4.4% by day 14 (Risk difference 1.9% (95%CI -9.3% to +13.2%) in
      AS+SP+PQ and AS+SP groups, respectively. CONCLUSION: Addition of primaquine to
      artemisinin combination treatment did not improve elimination of parasitaemia and
      prevention of gametocyte carriage in carriers with low-density parasitaemia in
      the dry season. TRIAL REGISTRATION: ClinicalTrials.gov NCT00330902.

PMID- 18074050
TI  - Developmental origins of health and disease (DOHaD).
AB  - OBJECTIVE: To present a new branch of scientific knowledge, known as the
      developmental origins of health and disease (DOHaD), covering its concepts, study
      methods and ethical considerations in addition to the prospects for this area of
      knowledge. SOURCES: A non-systematic review of the biomedical literature intended
      to identify historical and current references related to the subject under
      discussion. SUMMARY OF THE FINDINGS: Recent studies demonstrate associations
      between aggressions suffered during the initial phases of somatic development and
      amplified risk of chronic diseases throughout life, such as obesity, diabetes and
      cardiovascular diseases. A variety of models have been proposed in attempts to
      better explain these associations, such as the thrifty phenotype, programming and
      predictive adaptive response theories and the concept of match or mismatch. Some
      of the mechanisms possibly involved in these processes are: effects of the
      environment on gene expression, through epigenetic mechanisms; effects of
      hormonal signals transmitted to the fetus via the placenta or the newborn via
      lactation. CONCLUSIONS: DOHaD draws together information originating from many
      different areas of knowledge, proposing new investigative methodologies to
      elucidate the influence of adverse events that occur during early phases of human
      development on the pattern of health and disease throughout life. This new
      scientific field proposes new models of causality and of the mechanisms involved
      in the emergence and development of chronic diseases. The results of these
      investigations may result in a significant impact on the prevention of chronic
      diseases, and also on health promotion in different phases of life.

PMID- 18074035
TI  - Nitrosylcobalamin potentiates the anti-neoplastic effects of chemotherapeutic
      agents via suppression of survival signaling.
AB  - BACKGROUND: Nitrosylcobalamin (NO-Cbl) is a chemotherapeutic pro-drug derived
      from vitamin B12 that preferentially delivers nitric oxide (NO) to tumor cells,
      based upon increased receptor expression. NO-Cbl induces Apo2L/TRAIL-mediated
      apoptosis and inhibits survival signaling in a variety of malignant cell lines.
      Chemotherapeutic agents often simultaneously induce an apoptotic signal and
      activation of NF-kappaB, which has the undesired effect of promoting cell
      survival. The specific aims of this study were to 1) measure the anti-tumor
      effects of NO-Cbl alone and in combination with conventional chemotherapeutic
      agents, and to 2) examine the mechanism of action of NO-Cbl as a single agent and
      in combination therapy. METHODOLOGY: Using anti-proliferative assays,
      electrophoretic mobility shift assay (EMSA), immunoblot analysis and kinase
      assays, we demonstrate an increase in the effectiveness of chemotherapeutic
      agents in combination with NO-Cbl as a result of suppressed NF-kappaB activation.
      RESULTS: Eighteen chemotherapeutic agents were tested in combination with NO-Cbl,
      in thirteen malignant cell lines, resulting in a synergistic anti-proliferative
      effect in 78% of the combinations tested. NO-Cbl pre-treatment resulted in
      decreased NF-kappaB DNA binding activity, inhibition of IkappaB kinase (IKK)
      enzymatic activity, decreased AKT activation, increased caspase-8 and PARP
      cleavage, and decreased cellular XIAP protein levels. CONCLUSION: The use of NO
      Cbl to inhibit survival signaling may enhance drug efficacy by preventing
      concomitant activation of NF-kappaB or AKT.

PMID- 18074051
TI  - The journal impact factor today.

PMID- 18074052
TI  - Does critical illness and intensive care unit treatment contribute to
      neurocognitive and functional morbidity in pediatric patients?

PMID- 18074053
TI  - Indirect calorimetry: a potential but as yet unrealized technique for guiding
      nutritional management.

PMID- 18074054
TI  - The impact of admission to a pediatric intensive care unit assessed by means of
      global and cognitive performance scales.
AB  - OBJECTIVE: To assess the impact of admission to the pediatric intensive care unit
      (ICU) at the Hospital de Clinicas de Porto Alegre, RS, Brazil on children's
      cognitive and global performance. METHODS: An observational, longitudinal study
      of a sequential sample of critically ill children. The following indicators were
      used: the Pediatric Index of Mortality (PIM), for severity and risk of death at
      admission, the Pediatric Cerebral Performance Category (PCPC), for cognitive
      morbidity and the Pediatric Overall Performance Category (POPC), for global
      morbidity, at admission and at discharge. Morbidity related to the ICU was
      measured according to the difference between classifications at discharge and at
      admission (delta scores). The Kruskal-Wallis test was applied. RESULTS: A total
      of 443 patients were assessed, 54% of whom were male, with a median age of 12
      months (IQ 4-45), and a median ICU stay of 4.24 days (IQ 2.4-8). The mortality
      rate was 6.3%. The median PIM score was 2.36% (IQ 1-7). On admission, 46% of the
      patients had some degree of cognitive morbidity and 66% had some degree of global
      morbidity. At discharge there was 60% cognitive morbidity and 86% global
      morbidity. The assessment of ICU-related morbidity revealed that 25% of the
      patients had undergone cognitive changes while 41% had undergone global
      variations, at discharge compared with admission. CONCLUSIONS: Although affected
      by the elevated degree of morbidity at admission, the impact of the ICU stay was
      more significant in the global than in the cognitive domain. In the same manner,
      both risk of death at admission and length of stay had a significant effect on
      the morbidity of severely ill patients.

PMID- 18074055
TI  - Zinc serum levels and their association with vitamin A deficiency in preschool
      children.
AB  - OBJECTIVES: To identify the prevalence of zinc deficiency in a population with
      high prevalence of vitamin A deficiency; to verify whether zinc deficiency is
      associated with vitamin A deficiency in the population studied; to verify risk
      factors for zinc deficiency (sex, age, diarrhea and fever). METHOD: Cross
      sectional study of 182 healthy children aged > or = 24 months and < 72 months.
      Peripheral blood samples were obtained from fasting children to determine zinc
      serum levels. Information about presence of diarrhea and/or fever during the 15
      days preceding the study was also obtained. Vitamin A deficiency was identified
      by a serum 30-day dose-response test (+S30DR). RESULTS: Of the children studied,
      0.5% (1/182) presented zinc serum levels < 65 microg/dL; however, 74.7% (136/182)
      of them had vitamin A deficiency. Zinc serum levels were not correlated with
      retinol serum levels. Zinc serum levels were not changed by previous diarrhea
      and/or fever. There was no difference in zinc levels between boys and girls.
      Children aged between > or = 48 and < 60 months tended to have lower zinc serum
      levels than children of other ages. CONCLUSION: Zinc deficiency prevalence was
      low and did not represent a risk factor for vitamin A deficiency. Children aged
      between > or = 48 and < 60 months tended to have lower zinc serum levels than
      children of other ages. Zinc serum levels were not changed by previous diarrhea
      and/or fever.

PMID- 18074056
TI  - Incidence of hypotonic-hyporesponsive episodes associated to the combined DTP/Hib
      vaccine used in Brazilian National Immunizations Program.
AB  - OBJECTIVE: To evaluate the safety of a combined diphtheria-tetanus-whole cell
      pertussis-Haemophilus influenzae type b vaccine used on the Brazilian National
      Immunizations Program, chiefly the incidence of hypotonic-hyporesponsive
      episodes. METHOD: Follow-up of a cohort of 21,064 infants (20,925 or 99.7%
      adhered to the study protocol), within 48 hours of vaccination with diphtheria
      tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine in health care
      units in the City of Rio de Janeiro, to ascertain and investigate spontaneous and
      solicited severe adverse events. Each child was followed-up for one dose only.
      RESULTS: The rate of hypotonic-hyporesponsive episodes was 1/1,744 doses
      (confirmed cases) and 1/1,495 doses (confirmed plus suspect cases). The rate of
      convulsions was 1/5,231 doses. No cases of apnea were detected. These results are
      comparable to those found in the literature with diphtheria-tetanus-whole cell
      pertussis vaccine. CONCLUSION: The diphtheria-tetanus-whole cell pertussis
      Haemophilus influenzae type b vaccine under study can be safely used in the
      National Immunizations Program, according to the current precautions and
      contraindications.

PMID- 18074057
TI  - The use of bioelectrical impedance to detect excess visceral and subcutaneous
      fat.
AB  - OBJECTIVE: To analyze bioelectrical impedance performance in detecting the
      presence of excess visceral fat and overweight/obesity in young Brazilians and
      how its values are related with them. METHODS: Study sample consisted of 811
      adolescents of both genders (11 to 17 years of age). Nutritional status was
      determined based on triceps skinfold thickness (TSF), relative body fat
      (bioelectrical impedance), and excess visceral fat as determined by waist
      circumference. Statistical analysis was performed using means, standard
      deviations, linear correlation, Student's t test, and ROC curve. RESULTS:
      Bioelectrical impedance achieved good performance in identifying excess visceral
      fat associated with overweight/obesity in both genders, and was found to be more
      specific (male 92.4% and female 93.8%) than sensitive (male 86.1% and female
      71.8%). CONCLUSION: Our findings support the use of bioelectrical impedance to
      identify the presence of excess visceral and subcutaneous fat in adolescents.

PMID- 18074058
TI  - Gastroesophageal reflux and asthma in childhood: a study on their relationship
      using esophageal PH monitoring.
AB  - OBJECTIVES: This study aims at verifying the prevalence of gastroesophageal
      reflux in asthmatic children, and at determining the sensitivity and specificity
      of the reflux index for the diagnosis of gastroesophageal reflux disease.
      METHODS: Sixty-nine children, aged 1-5 years, with asthma, were studied by 24
      hour pH monitoring. The patients were randomly selected. RESULTS: Ages varied
      from 12.4 to 63.1 months, mean age = 30.79 months, and 62.3% were males.
      Gastroesophageal reflux was observed in 68.1% of the children. The patients were
      divided into two groups, moderate and severe asthma, and gastroesophageal reflux
      was diagnosed in 58.5 and 82.1% of the cases, respectively. Occult
      gastroesophageal reflux occurred in 31.8% of the cases. The reflux index showed
      an sensitivity of 89.4%, specificity of 95.5%, positive predictive value of 97.7%
      and negative predictive value of 80.8%. CONCLUSIONS: The results of this study
      indicate a relationship between gastroesophageal reflux and asthma, and suggest
      that the reflux index as a single parameter of pH monitoring has good sensitivity
      and specificity for the diagnosis of gastroesophageal reflux disease.

PMID- 18074059
TI  - Effect of intervention on the rates of breastfeeding of very low birth weight
      newborns.
AB  - OBJECTIVE: To describe an intervention to provide support and encouragement to
      mothers of preterm newborns and to evaluate its effect on breastfeeding rates in
      the first 6 months after hospital discharge. METHODS: One hundred newborns and
      their mothers were selected consecutively and prospectively according to order of
      birth. The mother-infant dyads were alternately assigned to one of two groups:
      one group received routine care (routine group), and the other group received the
      intervention (intervention group). The intervention consisted of individualized
      support in addition to the routine support provided in the Neonatology Service.
      Before delivery, one of the researchers was introduced to the mother and offered
      her information about the delivery. The researcher was also present at delivery,
      made an early visit to the infant in the intensive care unit, provided constant
      support for the mother to express breast milk and to maintain lactation, gave the
      mother information about maternal and infant hospital discharge, and provided
      outpatient follow-up after discharge. RESULTS: Thirty-six dyads completed the
      study. The characteristics of mothers and infants, as well as causes of
      exclusion, were similar in the two groups. In the routine group, 38.9% of the
      infants were being breastfed at hospital discharge, and median breastfeeding
      duration was 54 days. In the intervention group, 80.5% were being breastfed at
      discharge, and median breastfeeding duration was 91 days (p<0.01). CONCLUSIONS:
      Simple support measures offered to mothers during hospitalization and outpatient
      follow-up had a very positive effect on breastfeeding rates.

PMID- 18074060
TI  - Non-Hodgkin's lymphoma in childhood: clinical and epidemiological characteristics
      and survival analysis at a single center in Northeast Brazil.
AB  - OBJECTIVE: To describe the clinical and demographic characteristics of non
      Hodgkin's lymphoma patients diagnosed at the Pediatric Oncology Unit at the
      Instituto Materno-Infantil Professor Fernando Figueira (IMIP) over a 9-year
      period, and also to describe their survival rates and possible associations
      between the survival rates and the clinical and demographic characteristics
      analyzed in the study. METHODS: This was a cross-sectional study. Data were
      collected by a retrospective review of the charts of all 110 patients admitted to
      our unit during the period of May 1994 through May 2003. Probability of survival
      was calculated in accordance with the techniques of Kaplan-Meier, using log rank
      to evaluate differences between the groups. RESULTS: The average age was 6.1
      years. The male/female ratio was 2.4:1. The most frequent histological subtype
      was Burkitt's lymphoma. The majority of patients had been diagnosed with advanced
      disease (stage III or IV of Murphy's Classification) and was from rural areas.
      Family income per capita was lower than 1/2 minimum wage in 36.4% of cases;
      maternal illiteracy was observed in 12.7% of cases. The 5-year overall survival
      and disease-free survival rates were 70+/-4% and 68.4+/-4%, respectively. None of
      the clinical-demographic characteristics had a significant association with the
      probability of survival (p > 0.05). CONCLUSION: Children admitted to the IMIP
      seemed to be affected by non-Hodgkin lymphoma at a younger age, with a higher
      incidence of Burkitt's lymphoma and with survival rates similar to those
      described in the literature of developed countries. No clinical demographic
      characteristics had a statistically significant association with prognosis

PMID- 18074061
TI  - Prevalence of allergic rhinitis and its impact on the use of emergency care
      services in a group of children and adolescents with moderate to severe
      persistent asthma.
AB  - OBJECTIVE: To assess the prevalence of allergic rhinitis and the factors
      associated with the use of emergency care services by children and adolescents
      with acute asthma submitted to inhaled corticosteroid therapy. METHODS: A cross
      sectional study was conducted with 126 patients treated with beclomethasone
      dipropionate for 3 years. The factors associated with emergency care services in
      the third year of beclomethasone dipropionate treatment were assessed using
      logistic regression models. RESULTS: The prevalence of allergic rhinitis amounted
      to 74.6% (95%CI 65.9-81.7). The presence of allergic rhinitis (OR = 2.98, 95%CI
      1.10-8.06) and asthma severity (OR = 2.09, 95%CI 1.05-4.44) were independent
      factors for emergency care services. CONCLUSION: The prevalence of allergic
      rhinitis was high and that, combined with asthma severity, constituted the major
      risk factor for the necessity of emergency care services. Health professionals
      should attempt to make an early diagnosis of allergic rhinitis in asthmatic
      patients.

PMID- 18074062
TI  - Childhood cancer: maternal perceptions and strategies for coping with diagnosis.
AB  - OBJECTIVE: To investigate maternal perceptions of childhood cancer and strategies
      for coping in a pediatric unit in Recife, Brazil. METHODS: This descriptive
      exploratory study was conducted using qualitative methods. The reports of 10
      patients' mothers were analyzed according to a saturation sampling technique. The
      investigation was conducted in a pediatric oncology unit of the Instituto Materno
      Infantil Professor Fernando Figueira. Fieldwork was carried out from March to May
      2006 using observation techniques and recorded interviews to respond to three
      guiding questions. Content analysis and thematic coding were used, and recurrent
      themes were extracted from the categories identified. RESULTS: Mothers' ages
      ranged from 22 to 39 years, and two had only one child. The following themes
      stood out in the analysis of maternal perceptions of the moment that they were
      living: attitudes and feelings when the disease was diagnosed; information as
      support for coping; and social support. CONCLUSIONS: Maternal perceptions of
      childhood cancer revealed a shocking, painful and despairing experience, as well
      as a sensation of loss that made life meaningless. The sources of family support
      were individual religious beliefs, family members, healthcare team and friends.

PMID- 18074063
TI  - Infectious diseases and daycare and preschool education.

PMID- 18074065
TI  - Efficacy of new microprocessed phototherapy system with five high intensity light
      emitting diodes (Super LED).

PMID- 18074066
TI  - Authors' reply.

PMID- 18074067
TI  - Obstructive voiding symptoms are not predictive of elevated postvoid residual
      urine volumes.
AB  - The aim of this study is to explore the relationship between measured postvoid
      residual urine volumes (PVR) and self-reported bother from obstructive voiding
      symptoms (OS) using a retrospective chart review of patients presenting to our
      clinic from 2004 to 2005. Demographic, primary clinical diagnoses, PVR, and
      responses to the short form of the Pelvic Floor Distress Inventory (PFDI-20) were
      recorded. We considered a PVR > 150 ml to be elevated or consistent with urinary
      retention. We used Spearman's for correlations and Mann-Whitney test for
      independent groups. Six hundred thirty-six patients were included in the study.
      Individual PFDI-20 items, which inquire about obstructive voiding symptoms, had
      poor sensitivity (13-57%) and specificity (18-38%) for elevated PVR. Using
      logistic regression, age (beta = 0.04, p < 0.001) and stage > or = III prolapse
      (beta = 0.78, p < 0.05) were predictive factors for elevated PVR. Obstructive
      voiding symptoms have poor sensitivity and specificity for elevated PVR in women
      with pelvic floor disorders.

PMID- 18074069
TI  - The surgical anatomy of rectocele and anterior rectal wall intussusception.
AB  - The aim of the study was to analyse the dynamic anatomical supports of the
      posterior vaginal wall from the perspective of rectocele and rectal
      intussusception repair. Two groups of patients were studied. Group 1 (n = 24)
      with genuine stress incontinence but no major vault prolapse had
      vagino/proctomyograms and transperineal ultrasound examinations. Group 2 with
      vaginal vault prolapse, clinical rectoceles and obstructive defecation symptoms
      (n = 19 had single-contrast defecating proctography before and after posterior
      sling surgery. The posterior vaginal wall is suspended between perineal body,
      which underlies half its length, and uterosacral ligaments, which also support
      the anterior wall of rectum. Muscle forces stretch the vagina and rectum against
      the perineal body and uterosacral ligaments, creating shape and strength, like a
      suspension bridge. Postoperative proctogram studies indicated that anterior
      rectal wall intussusception has the same etiology as rectocele, deficient recto
      vaginal ligamentous support. Repair to uterosacral ligaments and perineal body
      should be considered with large rectoceles, anterior rectal wall intussusception
      and obstructive defecation disorders.

PMID- 18074070
TI  - Modified vaginal surgical technique for the management of the lateral vesico
      vaginal fistulae.
AB  - Obstetric fistulae vary significantly in size, location and condition of
      surrounding tissues. Traditional description of a genito-urinary fistula repair
      involves a fistula located in the midline of the vaginal wall, with minimal
      scarring or adhesions of the bladder/urethra to the surrounding vagina or pubic
      bone. Obstetric fistulae are often associated with significant scarring, situated
      laterally with adhesions to the pubic bone. This increases the difficulty in
      mobilising the bladder and in securing the lateral angles of the fistula during
      surgery. This paper describes a method to improve access to the laterally
      situated fistulae and thus facilitate surgical closure.

PMID- 18074068
TI  - Short-term outcome after transvaginal mesh repair of pelvic organ prolapse.
AB  - The objective of this study is to report on shortterm outcomes after pelvic organ
      prolapse repair using Prolift transvaginal mesh. A 3-year multicenter prospective
      cohort study was performed in 28 centers. Assessment preoperatively and at 2
      months postoperatively included the condition-specific pelvic organ prolapse
      quantification system (POP-Q) and a macroscopic inflammatory scale. Subjective
      outcome was measured using the urogenital distress inventory (UDI) and the
      incontinence impact questionnaire (IIQ-7). Surgical characteristics and adverse
      events during follow-up were registered in a separate protocol. The evaluation is
      based on the interim safety analysis and includes 2-month evaluations of 123
      cases. Pelvic organ perforation occurred in four cases (3.2%), three bladder
      injuries and one case of rectal perforation. At the 2-month follow-up, there were
      two cases of mesh exposure, an increase of mild-moderate granuloma formation in
      the operated areas (P < 0.003) but no cases of serious adverse tissue reactions
      related to the polypropylene mesh. Postoperative anatomical cure (defined as POP
      Q stage 0-1) was 87% after anterior repair, 91% after posterior repair and 88%
      after total repair. All quality of life aspects measured by the IIQ-7 improved 2
      months after surgery. Pelvic heaviness, vaginal bulging, and vaginal protrusion
      all decreased considerably (P < 0.001). There was also a significant improvement
      in several lower urinary tract symptoms and a decreased need for manually
      assisted defecation. This first report from an ongoing multicenter study suggests
      that transvaginal mesh surgery with the Prolift system is associated with
      satisfactory outcomes 2 months after surgery. There were no severe adverse events
      attributed to the polypropylene mesh.

PMID- 18074071
TI  - Different gene expression patterns in the bone tissue of aging postmenopausal
      osteoporotic and non-osteoporotic women.
AB  - PURPOSE: To identify genes that are differently expressed in osteoporotic and non
      osteoporotic human bone and to describe the relationships between these genes
      using multivariate data analysis. METHODS: Seven bone tissue samples from
      postmenopausal osteoporotic patients and 10 bone tissue samples from
      postmenopausal non-osteoporotic women were examined in our study. Messenger RNA
      was prepared from each sample and reverse transcribed to cDNA. The expression
      differences of 87 selected genes were analyzed in a Taqman probe-based
      quantitative real-time RT-PCR system. RESULTS: A Mann-Whitney U-test indicated
      significant differences in the expression of nine genes (p < or = 0.05). Seven of
      these nine genes-ALPL, COL1A1, MMP2, MMP13, MMP9, PDGFA, NFKB1-were significantly
      downregulated in the bone tissue of osteoporotic women, while CD36 and TWIST2
      were significantly upregulated in osteoporotic patients. Principal components
      analysis was used to evaluate data structure and the relationship between
      osteoporotic and non-osteoporotic phenotypes based on the multiple mRNA
      expression profiles of 78 genes. Canonical variates analysis demonstrated further
      that osteoporotic and non-osteoporotic tissues can be distinguished by expression
      analysis of genes coding growth factors/non-collagen matrix molecules, and genes
      belonging to the canonical TGFB pathway. CONCLUSION: Significant differences
      observed in gene expression profiles of osteoporotic and non-osteoporotic human
      bone tissues provide further insight into the pathogenesis of this disease.
      Characterization of the differences between osteoporotic and non-osteoporotic
      bones by expression profiling will contribute to the development of diagnostic
      tools in the future.

PMID- 18074072
TI  - Three-dimensional reconstructive methods in the visualization of anterolateral
      thigh flap.
AB  - INTRODUCTION: Developments in the field of digitalized technique and three
      dimensional (3D) reconstruction methods allowed a precise description of anatomy
      structures. With the development of computer reconstructive techniques, we could
      get more precise anatomic images. Digitized visible models of these structures
      can be as a useful tool in clinical training. The purpose of this study was to
      observe the anatomy of arteria circumflexa femoris lateralis (ACFL) flap and to
      discuss the methods in the visualization of anterolateral thigh (ATL) flap by
      digitalized technique. METHODS: Six adults volunteer underwent contrast-enhanced
      CT angiography of pelvic and lower limbs utilizing a 64-row multi-slice spiral CT
      after median cubital vein injection with Ultravist (3.5 ml/s). 2D images from
      these data in Dicom format were transformed into computer. Next two adult fresh
      cadaver specimens, one male and one female, were subject to radiographic CT
      scanning before and after perfused with lead oxide-gelatine mixture, whose
      collimation are 0.5 mm (120 kV, 110 mA, 512 x 512 matrix). Through Amira 3.1
      (TGS) software, the 2D images in Dicom format were transformed into the 3D models
      of the entire region. The structures of arteria circumflexa femoris lateralis
      (ACFL) were observed and the digitized visible models of ALT flap were
      established through 3D computerized reconstructions methods from these data using
      Amira 3.1 software. Then merging volume rendering with surface rendered
      reconstruction from lead oxide-gelatine mixture perfusion database. RESULTS: The
      3D reconstructed visible models established from these datasets perfectly
      displayed the characteristic of ACFL and ALT flap anatomy. CONCLUSION: The
      digitized models could offer the anatomy of ALT flap perfectly, and the
      reconstructed methods may be used in other flap reconstruction with 3D
      demonstration.

PMID- 18074073
TI  - Variations of the bilateral testicular veins: embryological and clinical
      considerations.
AB  - Variations of the bilateral testicular veins were observed during routine
      dissection of the posterior abdominal wall in a 77-year-old male Japanese
      cadaver. The right testicular vein consisted of the lateral and medial testicular
      veins. The right lateral testicular vein drained into the right renal vein. The
      right medial testicular vein accompanied the right testicular artery to ascend
      obliquely and drained into the left aspect of the inferior vena cava. The left
      testicular vein was composed of the lateral, middle and medial testicular veins.
      Three left testicular veins accompanied the left testicular artery to course
      cranially and then finally drained into the left renal vein.

PMID- 18074074
TI  - Multifocal central and peripheral demyelination associated with hepatitis C virus
      infection.

PMID- 18074075
TI  - Comparison of interferon beta products and azathioprine in the treatment of
      relapsing-remitting multiple sclerosis.
AB  - We compared the relative efficacy of interferon beta (IFNbeta) products and
      azathioprine (AZA) in the treatment of relapsing- remitting multiple sclerosis
      (RRMS). Ninety-four previously untreated patients of short duration with RRMS
      were randomly allocated to the two treatment groups. The first group received
      IFNbeta products (Betaferon,Avonex or Rebif); the second group received AZA for
      12 months. Response to treatment was assessed at 3, 6, and 12 months after
      starting therapy. The mean number of relapse during one year of the study was
      lower in the AZA group than in the IFNbeta products group (0.28 vs. 0.64, P <
      0.05). After 12 months, 57.4% of patients receiving IFNbeta products remained
      relapse free compared with 76.6% of those given AZA. The Expanded Disability
      Status Scale (EDSS) decreased by 0.30 units in IFNbeta-treated patients (P <
      0.05) and 0.46 in AZAtreated patients (P < 0.001). Treatment with IFNbeta
      products and AZA significantly reduces the relapse rate and EDSS score in
      patients with RRMS, while AZA is more effective than the IFNbeta formulations.

PMID- 18074076
TI  - A brief compound test for assessment of autonomic and sensory-motor dysfunction
      in familial amyloid polyneuropathy.
AB  - BACKGROUND: Familial amyloid polyneuropathies (FAP) patients manifest progressive
      sensory-motor length dependent polyneuropathy and severe autonomic dysfunction.
      In this setting the autonomic manifestations include mainly postural hypotension,
      nausea and vomiting, diarrhea and constipation, sphincter distur- bances and
      erectile dysfunction. Reproducible quantitative evaluation of signs and symptoms
      are necessary for the assessment of treatment efficacy. OBJECTIVE: To determine
      the reliability of a new compound test cumulating evaluation of autonomic and
      sensorymotor dysfunction in FAP. METHODS: Compound Autonomic Dysfunction Test
      (CADT) is a new questionnaire to evaluate the main symptoms of autonomic
      dysfunction observed in FAP. A separate functional questionnaire assesses the
      disability due to the sensorymotor deficit (Modified Norris Test; MNT). The
      compound test takes approximately 10 minutes to perform. In this prospective
      study, we enrolled consecutively 60 FAP patients to test interexaminer
      reliability, i.e., both questionnaires rated independently by 2 examiners. We
      also evaluate the reliability of testing patients face to face and by phone call,
      by the same examiner. RESULTS: Interexaminer reliabilities tested were high
      (ICC=0.92 for the CADT, p < 0.001; and ICC = 0.99 for the MNT, p < 0.001). In
      addition, testing by phone as compared to testing during the initial medical
      visit by the same investigator gave similar results (ICC = 0.91 for the CADT, p <
      0.001; and ICC = 0.98 for the MNT, p < 0.001). CONCLUSION: In FAP, the CADT and
      the MNT have good reliability inter-investigators as well as between face to face
      and by phone call, by the same examiner. This newly designed compound test is a
      simple and reproducible scale which is adapted to evaluate the main neuropathic
      manifestations and will be useful for assessment of future treatments in this
      condition.

PMID- 18074078
TI  - [Gerontologic studies].

PMID- 18074080
TI  - [Study concepts for social work with elderly people and planning of a new
      gerontological master program at the University of Dortmund].
AB  - This article presents previous experiences regarding the study course Social
      Gerontology (bWSG) at the University of Dortmund. After a short historical
      outline the focus will be on a critical examination of the success of the study
      course. Finally, new developments at the University of Dortmund will be
      presented, among others the concept development of a new master programme "Ageing
      Societies" (working title).

PMID- 18074079
TI  - [Status report on gerontological master programmes--Bologna Process, profile and
      peculiarities].
AB  - The article provides an overview of the development stage of gerontological
      university master programmes, under consideration of the ongoing Bologna Process.
      Educational structures in Germany, the universities of which were the first to
      offer gerontological master programmes, developed differently than those in
      Austria and Switzerland, where age-and-ageing-related disciplines were mostly
      offered by (pedagogic and parochial) academies. The article first focuses on an
      analysis of the existing and planned gerontological study courses, in all three
      countries, based on the respective profiles, emphases and specialisations in the
      gerontological master programmes. Special attention is also given to the
      question, whether the demands, placed on gerontological university studies by
      demographic changes and age-related structural changes, are sufficiently met, as
      well as to the compatibility of the gerontological master programmes with basic
      socio-scientific university training, and their professional applicability. It
      seems evident that the efforts made by universities and by technical colleges to
      teach with a strong focus on existing practice, have engendered a great variety
      of adult-education concepts. The future will show which of these educational
      approaches will stand their ground, from the point of view of the students, as
      well as on the side of the labour market.

PMID- 18074081
TI  - [Gerontological master programmes at German universities of applied sciences
      using the example of the master program "Applied Gerontology" in Freiburg].
AB  - In this article, the joint applied gerontology master program of Freiburg's two
      universities of applied sciences is introduced. Its particular profile is
      characterised, but is also reflected critically with regard to its position in
      German academics.

PMID- 18074082
TI  - [Qualifying a broad range of professionals to master the demographic challenge:
      the Master's course of Gerontology at the University of Applied Sciences in
      Cottbus].
AB  - Our new five-semester MA course in gerontology has been designed as a programme
      of continuing education for professionals from various fields being confronted
      with hitherto unknown challenges by "the greying of societies". While many
      services are directed to meet the needs of older clients, the elderly also
      represent a huge potential of various resources indispensable to society. Coming
      from various fields of study and different positions (mainly management or self
      employed), our students engage in an interdisciplinary discourse from the
      beginning which helps them acquire knowledge and competencies to later deal with
      the complex tasks requiring interdisciplinary problem solving skills and
      establish "best practice" models. Universities are expected to engage in
      continuing education, thus being the places of choice for postgraduate studies in
      gerontology, which also offer research opportunities. Universities of Applied
      Sciences, intended to foster regional development, integrate students into
      applied research projects thereby transferring knowledge and skills to reach out
      to the community. During the first four semesters, each student enrolled in the
      MA Gerontology course plans, implements and evaluates a project of his/her own.
      This ensures the integration of gerontological knowledge and research methods and
      helps to extend and improve practical skills. We support students by regular
      coaching and supervision.

PMID- 18074083
TI  - [Academic study programs in gerontology and geriatrics in Austria].
AB  - This article describes the situation of academic study programs in gerontology
      and geriatrics in Austria. University formation in these areas is at the very
      beginning. Due to the lack of institutionalization of gerontology and geriatrics
      at the university level, the study programs were developed by non-university
      institutions. The studies are mostly at the post-gradual level and are practice
      oriented.

PMID- 18074084
TI  - [Interdisciplinary approaches in gerontology--developments in Switzerland].
AB  - Even though a professional approach in Swiss gerontological work was established
      early on in the process, institutional entrenchment of gerontological research
      and education happened very late; this is particularly true for the German
      speaking part of Switzerland. Further development of gerontological research did
      not take place before the 1990s, and it took several years longer before
      gerontological master programmes were institutionalised at the universities. The
      contribution describes and analyses the development and current situation of
      gerontological studies in Switzerland (a comparatively small state, which will
      continue to depend on close cooperation with its neighbouring states in order to
      develop gerontology).

PMID- 18074085
TI  - [Studies in gerontology at Vechta University].
AB  - The University of Vechta has developed and introduced innovative Bachelor and
      Master studies in gerontology in accordance with the Bologna process. The
      Bachelor studies provide first degree courses and place great emphasis on the
      practical and problem-oriented application of knowledge. Therefore, studies in
      social sciences, economics and law are interlinked. The Master studies are
      explicitly research oriented and consecutive and are based on the combination of
      individual, organisational and societal aspects of ageing in the sense of a
      multilevel analysis. The research orientation is strengthened through the co
      operation with the research centre "Ageing and Society" (CAG) at Vechta
      University.

PMID- 18074086
TI  - [Geriatric treatment in hospitals?--medical, legal, and economic aspects].
AB  - Multimorbidity and functional impairment in geriatric patients regularly
      necessitate a combination of acute medical care and functional therapy. In
      Germany, comprehensive geriatric care is usually provided in hospitals, but also
      in clinical rehabilitation units. Different payment systems (diagnosis related
      groups in hospitals, day-to-day charges in rehabilitation centers) have
      precipitated a discussion on the separation of the acute phase from the
      rehabilitative phase of the disease with medical issues prevailing in the former
      and functional training in the latter. In geriatric patients, however, medical
      treatment of acute and chronic diseases should be continuously combined with
      functional therapy from the beginning of the hospital stay (i. e. early
      rehabilitation). Thus, acute hospital treatment followed by rehabilitation in a
      different institution, a method frequently used with younger patients with single
      defined diagnoses, has shown to be disadvantageous in geriatric patients. Some
      federal states in Germany favor the concept of one-step comprehensive hospital
      care including rehabilitation. As discussed in the article in detail, this
      procedure is in full accordance with the German social law.

PMID- 18074087
TI  - [Patient characteristics and factors associated with unfavourable in-hospital
      rehabilitation therapy outcome in very old geriatric patients with first-ever
      ischemic stroke--a retrospective case-control study].
AB  - AIM: A retrospective case-control study was performed to evaluate patient
      characteristics or other factors possibly predicting unfavourable outcome of
      rehabilitation therapy in geriatric stroke patients. A total of 47 patients with
      first-ever ischaemic stroke were included in each group, mean age 81 years, 79%
      females, basic functional competence level </=65 points as assessed by the
      Barthel Index total score on admission. Per definition, the cases did not improve
      in functional competence level or even deteriorated during the hospital stay,
      whereas the patients of the control group increased in Barthel Index total score
      level by at least 10 points. METHODS: Beginning on January 1, 2003, patients were
      recruited from all consecutively admitted patients using the data from the
      hospital information system and information from the Gemidas project (quality
      assurance system). From the complete case notes, information was extracted on
      grade of neurological deficit, particular clinical signs and stroke symptoms,
      relevant comorbidity, medication at the time of patients' death or hospital
      discharge, complications including its therapeutic consequences, and patients'
      discharge destination. We performed uni-variate comparisons and a logistic
      regression analysis. RESULTS: Elderly in-hospital patients with first-ever
      ischaemic stroke and poor therapeutic outcome showed a high prevalence of severe
      neurological deficits and poor functional competence level on admission. During
      the hospital stay, these patients even suffered more often and more severe
      nonneurological and neurological complications. These were associated with high
      mortality and the need of further reference to other hospital clinical
      departments such as the intensive care unit. Hospital acquired infections
      accounted for more than half of the complications. Pneumonia, dementive diseases,
      and incontinence were the factors revealed to be associated with unfavourable
      therapeutic outcome. CONCLUSIONS: The results of this retrospective evaluation
      shows that geriatric patients with first-ever ischaemic stroke with severe
      neurological deficits and poor functional competence level on admission suffered
      frequently from non-neurological and neurological complications. Particularly in
      elderly stroke patients with dysphagia, dementive diseases and/or cognitive
      impairment, there is a need of intensified preventive measures to avoid
      complications.

PMID- 18074088
TI  - [Report of the German Societey for Gerontology and Geriatrics e.V.]].

PMID- 18074089
TI  - [Federal working group for Clinical Geriatric Establishments e.V].

PMID- 18074090
TI  - [Report of the of Dachverband Gerontological and Geriatric Scientific Society of
      Germany e. V. (DVGG) ].

PMID- 18074094
TI  - Tumor necrosis factor alpha is not a pathogenic determinant in acute lethal
      encephalitis induced by a highly neurovirulent strain of mouse hepatitis virus.
AB  - To investigate the role of tumor necrosis factor alpha (TNFalpha) in the
      pathogenesis of acute viral encephalitis, TNFalpha-deficient mice were infected
      with a highly neurovirulent strain of mouse hepatitis virus, JHM, and compared
      with JHM-infected C57BL/6 mice as controls. All the JHM-infected mice had
      succumbed to infection by 6 days postinfection. The virus replication kinetics,
      histopathological changes and mRNA expression levels of proinflammatory cytokines
      in the brain did not differ between TNFalpha-deficient and control C57BL/6 mice.
      These results suggest that TNFalpha is not a pathogenic determinant in JHM
      induced acute lethal encephalitis.

PMID- 18074095
TI  - Hepatitis C virus non-structural protein-2 activates CXCL-8 transcription through
      NF-kappaB.
AB  - Hepatitis C is a devastating disease worldwide. Proteins encoded by the etiologic
      agent, hepatitis C virus (HCV), are believed to play important roles in HCV
      associated pathogenesis. However, the biological functions of the non-structural
      protein-2 (NS2) encoded by HCV are not well characterized. Here, we show that HCV
      NS2 protein activates CXCL-8 (interleukin-8, IL-8) transcription in HepG2 cells
      as measured by reverse transcription-polymerase chain reaction and IL-8 promoter
      luciferase reporter assays. Furthermore, when the kappaB site on the IL-8
      promoter was eliminated by mutagenesis or when intracellular NF-kappaB activity
      was suppressed by an inhibitor, NS2 did not activate the IL-8 promoter,
      suggesting a role of NF-kappaB in this process. These results prompted us to
      hypothesize that HCV NS2 might be able to activate NF-kappaB. This hypothesis was
      tested by determination of NF-kappaB-driven reporter gene expression and NF
      kappaB p65 subunit subcellular localization after HCV NS2 expression. Indeed, NS2
      could up-regulate NF-kappaB-driven luciferase activity and was associated with
      p65 nuclear localization. These results demonstrate that HCV NS2 up-regulates IL
      8 transcription through NF-kappaB. This newly identified function increases our
      understanding of the role of HCV NS2 protein in virus-host interactions.

PMID- 18074096
TI  - Complete nucleotide sequence of a new double-stranded RNA virus from the rice
      blast fungus, Magnaporthe oryzae.

PMID- 18074097
TI  - Lack of alternative coreceptor use by pediatric HIV-1 R5 isolates for infection
      of primary cord or adult peripheral blood mononuclear cells.
AB  - HIV-1 infection of neonates results in an extended acute period of virus
      replication, frequent neurological problems and reduced survival compared to
      adults. In adults, R5 viruses mainly infect CCR5(+) CD4(+) memory T-cells. In
      neonates, CCR5(+) memory T-cells form a substantially smaller fraction of total
      lymphocytes. We therefore tested whether alternative coreceptors confer infection
      of lymphocytes by pediatric isolates. Pediatric HIV-1 R5 isolates failed to
      replicate in Delta32/Delta32 CCR5 PBMCs or in cord PBMCs treated with a CCR5
      inhibitor. These results do not indicate a role for alternative coreceptors and
      provide support for CCR5 inhibitors in the therapy of HIV-1(+) neonates.

PMID- 18074098
TI  - An insufficient anti-inflammatory cytokine response in mouse brain is associated
      with increased tissue pathology and viral load during Japanese encephalitis virus
      infection.
AB  - Infection of the central nervous system with Japanese encephalitis virus (JEV)
      results in fatal encephalitis in humans. No reports exist describing the sequence
      of pathological changes and their correlation to the immune response in the brain
      following infection with JEV. In this report, we analyzed inducible nitric oxide
      synthase (iNOS) mRNA, proinflammatory (IFN-gamma, TNF-alpha) and anti
      inflammatory (IL-4, IL-10) cytokine expression, viral load, and the correlation
      of these factors with the major histopathological changes in brain of JEV
      challenged mice at different time points during infection. We report for the
      first time that in JE, there is a progressive decline in the level of IL-4. The
      extent of progressive decrease in IL-4 and IL-10 level following viral infection
      is inversely correlated to the increased level of proinflammatory cytokines and
      histopathological changes with negative consequences following viral infection.
      In contrast, proinflammatory mediators like IFN-gamma and TNF-alpha were
      significantly upregulated (P < 0.05). A negative correlation between IFN-gamma
      and iNOS indicates their independent actions during JEV infection. To conclude,
      an insufficient anti-inflammatory cytokine response indicated by IL-4 and IL-10
      in the brain is associated with increased tissue pathology and viral load, which
      regulates inflammatory responses driven by IFN-gamma in concert with TNF-alpha to
      cause brain tissue damage.

PMID- 18074099
TI  - Characterization of complete sequences of RNA 1 and RNA 2 of citrus variegation
      virus.

PMID- 18074100
TI  - Understanding the pathophysiology of vasomotor symptoms (hot flushes and night
      sweats) that occur in perimenopause, menopause, and postmenopause life stages.
AB  - Vasomotor symptoms (VMS), commonly called hot flashes or flushes (HFs) and night
      sweats, are the menopausal symptoms for which women seek treatment during
      menopause most often. VMS are a form of temperature dysfunction that occurs due
      to changes in gonadal hormones. Normally, core body temperature (CBT) remains
      within a specific range, oscillating with daily circadian rhythms. Physiological
      processes that conserve and dissipate heat are responsible for maintaining CBT,
      and tight regulation is important for maintenance of optimal internal organ
      function. Disruption of this tightly controlled temperature circuit results in
      exaggerated heat-loss responses and presents as VMS. The mechanistic role related
      to changes in gonadal hormones associated with VMS is not understood. Hormone
      therapy is the most effective treatment for VMS and other menopausal symptoms.
      Estrogens are known potent neuromodulators of numerous neuronal circuits
      throughout the central nervous system. Changing estrogen levels during menopause
      may impact multiple components involved in maintaining temperature homeostasis.
      Understanding the pathways and mechanisms involved in temperature regulation,
      probable causes of thermoregulatory dysfunction, and "brain adaptation" will
      guide drug discovery efforts. This review considers the processes and pathways
      involved in normal temperature regulation and the impact of fluctuating and
      declining hormones that result in VMS during the menopausal transition.

PMID- 18074101
TI  - Gene dosage change of TPTE and BAGE2 and breakpoint analysis in Robertsonian Down
      syndrome.
AB  - Only 4% of Down syndrome (DS) cases have a Robertsonian translocation (ROB). The
      aim of this study was to define the possible breakage area in 21p where ROB
      occurs. We prospectively and consecutively collected ten cases ROB DS from three
      medical centers. Of the ten DS children, six were de novo (60%), and four were
      due to paternal or maternal inheritance (40%). They consisted of four
      der(21q;21q), four der(14q;21q), one der(13q;21q), and one der(21q;22q). The
      origin of the extra chromosome 21q was maternal in five of six de novo ROB and
      paternal in one case. All four der(21;21) ROB DS were an isochromosome. The
      result of gene dosage change by real-time quantitative polymerase chain reaction
      (PCR) was compatible with array-comparative genomic hybridization in one case. We
      further used real-time PCR to detect the copy number of TPTE and BAGE2 located on
      21p11 and SAMSN1 on 21q11. The ratio of copy number in 21p:21q was 1:3 in
      der(21q;21q) but 2:3 in der(13q;21q), der(14q;21q), and der(21q;22q). Our
      preliminary results demonstrated the critical breakpoint of chromosome 21
      involving ROB might lie between BAGE2 and the centromere, located from 10.1 to
      12.3 Mb.

PMID- 18074103
TI  - Headache caused by handling the pesticide Antracol Combi WP 76: a case report.
AB  - We report on headache caused by the pesticide Antracol Combi WP 76. A headache
      caused by handling of pesticides should be distinguishable from migraine and
      headaches from other causes. This 29-year-old woman, who handled pesticides,
      presented with very strong headache with nausea and vomiting. Poisoning by this
      pesticide cannot be proven toxicologically, and there is no antidote. Following
      isolation from the pesticide and abundant hydration, the pain gradually
      decreased. History, clinical signs and neuroradiological examinations excluded
      other possible causes of the headache. In treatment of patients in rural areas,
      attention should also be paid to the pesticide Antracol Combi WP 76 as a possible
      cause of headaches.

PMID- 18074102
TI  - Genome analysis and its significance in four unicellular algae, Cyanidioschyzon
      [corrected] merolae, Ostreococcus tauri, Chlamydomonas reinhardtii, and
      Thalassiosira pseudonana.
AB  - Algae play a more important role than land plants in the maintenance of the
      global environment and productivity. Progress in genome analyses of these
      organisms means that we can now obtain information on algal genomes, global
      annotation and gene expression. The full genome information for several algae has
      already been analyzed. Whole genomes of the red alga Cyanidioschyzon [corrected]
      merolae, the green algae Ostreococcus tauri and Chlamydomonas reinhardtii, and
      the diatom Thalassiosira pseudonana have been sequenced. Genome composition and
      the features of cells among the four algae were compared. Each alga maintains
      basic genes as photosynthetic eukaryotes and possesses additional gene groups to
      represent their particular characteristics. This review discusses and introduces
      the latest research that makes the best use of the particular features of each
      organism and the significance of genome analysis to study biological phenomena.
      In particular, examples of post-genome studies of organelle multiplication in C.
      merolae based on analyzed genome information are presented.

PMID- 18074104
TI  - Validation of a Georgian language headache questionnaire in a population-based
      sample.
AB  - In a pilot phase of a survey of the prevalence of primary headache disorders in
      the Republic of Georgia, we validated a Georgian language questionnaire for
      migraine (MIG), tension-type headache (TTH), MIG+TTH and trigeminal autonomic
      cephalalgias (TAC). A population-based sample of 186 people with headache
      completed the questionnaire and were blindly examined by one of two headache
      experts. The questionnaire diagnoses were: MIG 49, TTH 76, MIG+TTH 45 and TAC 16.
      The physicians' diagnoses were: MIG 59, TTH 77, MIG+TTH 34, TAC 2 and
      "symptomatic headache" in 14 subjects. Sensitivity and specificity for MIG were
      0.75 and 0.96, for TTH 0.79 and 0.86, and for MIG+TTH 0.61 and 0.84 respectively.
      Of 16 TAC diagnoses, the physicians confirmed cluster headache in two patients
      only. The questionnaire can be utilised to investigate the prevalence of MIG and
      of TTH. It offers preliminary screening only for TAC, which should be confirmed
      during a face to face examination.

PMID- 18074105
TI  - Continuous intrathecal treatment with methotrexate via subcutaneous port:
      implication for leptomeningeal dissemination of malignant tumors.
AB  - Use of intrathecal (IT) chemotherapy combined with radiotherapy can extend
      survival of patients with untreated leptomeningeal dissemination of malignant
      tumors from one month to two to six months. The goal of the present study was to
      determine the effect of continuous IT (CIT) via a subcutaneous port that was
      placed using a neuronavigation system. Twenty patients with leptomeningeal
      dissemination (primary disease: 10 cancers, 6 gliomas and 4 lymphomas) were given
      2-7 cycles of continuous IT (CIT) with methotrexate (MTX; 10 mg) administered
      into the lateral ventricle for 5 consecutive days biweekly. The concentration of
      MTX in the lateral ventricle was 7 to 10 x 10(-6 )M from Day 1 to 4. Response to
      this therapy included 6 patients with complete remission, 7 with progressive
      disease, and 7 with stable disease. Kaplan-Meier analysis revealed a median
      overall survival of 8 months while the overall survival rate for leptomeningeal
      specific death or for metastasis from cancer was 13 or 5 months, respectively.
      Complications of CIT with MTX were relatively low (<0.5%), and nausea and
      vomiting did not occur in any of the patients. In conclusion, CIT with 10 mg MTX
      via subcutaneous port for 5 days may improve the therapeutic effect and reduce
      the complications associated with treatment of leptomeningeal dissemination from
      malignant tumors. This would be a safe technique with possible implications that
      bear repeating more patients.

PMID- 18074106
TI  - Giant skull metastasis of Hurthle cell variant of thyroid's papillary carcinoma.
AB  - We report the MRI and pathological findings of a 53-year-old woman with a giant
      skull metastasis from a Hurthle cell variant of thyroid's papillary carcinoma. To
      our knowledge, this is the first case of a skull metastasis from a Hurthle cell
      variant of thyroid's papillary carcinoma.

PMID- 18074107
TI  - Effects of inductive bias on computational evaluations of ligand-based modeling
      and on drug discovery.
AB  - Inductive bias is the set of assumptions that a person or procedure makes in
      making a prediction based on data. Different methods for ligand-based predictive
      modeling have different inductive biases, with a particularly sharp contrast
      between 2D and 3D similarity methods. A unique aspect of ligand design is that
      the data that exist to test methodology have been largely man-made, and that this
      process of design involves prediction. By analyzing the molecular similarities of
      known drugs, we show that the inductive bias of the historic drug discovery
      process has a very strong 2D bias. In studying the performance of ligand-based
      modeling methods, it is critical to account for this issue in dataset
      preparation, use of computational controls, and in the interpretation of results.
      We propose specific strategies to explicitly address the problems posed by
      inductive bias considerations.

PMID- 18074108
TI  - Transplantation of NGF-gene-modified bone marrow stromal cells into a rat model
      of Alzheimer' disease.
AB  - It is well known that bone marrow stromal cells (BMSC) grafted into the
      hippocampus of the rat model of Alzheimer's disease (AD) could survive and
      differentiate into cholinergic neurons as well as contribute towards functional
      restoration. The present study evaluated the effects of BMSC as a seed cell
      modified by nerve growth factor (NGF) gene into the hippocampus of AD rats. The
      beta-amyloid protein was injected bilaterally into the rat hippocampus to
      reproduce the AD model. After the human total RNA was extracted, the NGF gene was
      amplified by reverse transcription-polymerase chain reaction, then cloned into
      the pcDNA3. BMSC derived from a green fluorescence protein transgenic mouse were
      isolated, cultured, identified, and transfected by the NGF recombinant. The NGF
      gene-modified BMSC were then transplanted into the hippocampus of AD rats. The
      results showed that implanted BMSC survived, migrated and expressed NGF as well
      as differentiated into ChAT-positive neurons. A significant improvement in
      learning and memory in AD rats was also seen in NGF-gene-modified BMSC group,
      when compared with the BMSC group. The present findings suggested that BMSC
      provided an effective carrier for delivery of NGF into AD rats, and the
      administration of NGF-gene-modified BMSC may be considered as a potential
      strategy for the development of effective therapies for the treatment of AD.

PMID- 18074109
TI  - Expression of CAPON after spinal cord injury in rats.
AB  - The adaptor protein, carboxy-terminal PDZ ligand of nNOS (CAPON), regulates the
      distribution of neuronal nitric oxide synthase (nNOS) that increased after spinal
      cord injury (SCI) and produces the key signaling molecule nitric oxide (NO). But
      little is known about the role of CAPON in the pathological process of SCI. The
      main objective of the present study was to investigate expression of CAPON and
      nNOS in a spinal cord contusion model in adult rats. Real time-polymerase chain
      reaction (PCR) and Western blot analysis revealed that mRNA and protein for CAPON
      increased at 2 h after SCI and reached the peak at 8 h, gradually recovered to
      the baseline level at 14 days. The expression of nNOS mRNA and protein was
      similar to that of CAPON. During the peak expression, CAPON mRNA was found in the
      ventral horn, mediate zone, dorsal horn, and white matter by in situ
      hybridization. Immunofluorescence showed that CAPON was colocalized with nNOS in
      neurons, oligodendrocytes, and some astrocytes of spinal cord tissues within 5 mm
      from the epicenter. Interaction between CAPON and nNOS was also detected by co
      immunoprecipitation. Thus, the transient expression of high levels of CAPON may
      provide new insight into the secondary response after SCI.

PMID- 18074110
TI  - Trabecular bone microarchitecture in female collegiate gymnasts.
AB  - Using high-resolution magnetic resonance imaging, we observed more developed
      trabecular bone microarchitecture in the proximal tibia of female collegiate
      gymnasts vs. matched controls. This suggests that high-load physical activity may
      have a positive effect on the trabecular microarchitecture in weight-bearing
      bone. INTRODUCTION: Participation in physical activities that overload the
      skeleton, such as artistic gymnastics, is associated with increased areal bone
      mineral density (aBMD); however, the status of trabecular microarchitecture in
      the weight-bearing bone of gymnasts is unknown. METHODS: Eight female collegiate
      artistic gymnasts and eight controls matched for age, height, body mass, gender
      and race were recruited for the study. Apparent trabecular bone volume to total
      volume (appBV/TV), trabecular number (appTb.N), thickness (appTb.Th) and
      trabecular separation (appTb.Sp) were determined using high resolution magnetic
      resonance imaging. Areal bone mineral density, bone mineral content (BMC) and
      bone area in the proximal tibia were determined using dual-energy X-ray
      absorptiometry. Group differences were determined using t-tests. The magnitude of
      group differences was expressed using Cohen's d (d). RESULTS: Gymnasts had higher
      appBV/TV (13.6%, d = 1.22) and appTb.N (8.4%, d = 1.45), and lower appTb.Sp
      (13.7%, d = 1.33) than controls (p < 0.05). Gymnasts had higher aBMD and BMC in
      the proximal tibia, although the differences were smaller in magnitude (d = 0.75
      and 0.74, respectively) and not statistically significant (p > 0.05). CONCLUSION:
      The findings suggest that high-load physical activity, such as performed during
      gymnastics training, may enhance the trabecular microarchitecture of weight
      bearing bone.

PMID- 18074111
TI  - Association of polymorphism in the thermolabile 5, 10-methylene tetrahydrofolate
      reductase gene and hyperhomocysteinemia with coronary artery disease.
AB  - OBJECTIVE: To determine the incidence of methylene tetrahydrofolate reductase
      (MTHFR) gene 677C-->T polymorphism and plasma homocysteine (Hcy) levels in a
      group of subjects who underwent coronary angiography, in an attempt to establish
      a correlation between these parameters and the severity of coronary artery
      disease (CAD) and to investigate the correlation between hyperhomocysteinemia
      (HHcy) and the presence of 677C-->T polymorphism. BACKGROUND: Elevated plasma Hcy
      level is an independent risk factor for CAD. A common mutation (677C-->T) in the
      gene coding for MTHFR has been reported to reduce the enzymatic activity and is
      associated with elevated levels of Hcy, especially in subjects with low folate
      intake. METHODS: The study group comprised of 84 patients with CAD and 100 age
      and-sex matched controls who had no history or clinical evidence of CAD and/or
      MI. DNA was extracted from peripheral blood and genotypes were determined by
      polymerase chain reaction, restriction mapping with Hinf1, and gel
      electrophoresis. Conventional risk factors for CAD were prospectively documented.
      RESULTS: Allele and genotype frequencies in cases and control subjects were
      compatible with Hardy-Weinberg equilibrium. The frequencies of TT, CT, and CC
      genotypes among CAD patients were 4.8, 27.4, and 67.8% and in controls were 1.0,
      19.0, and 80%. Hcy levels were higher in patients with triple-vessel disease
      compared to single and double vessel disease (P = 0.002). Multivariate analyses
      identified HHcy, diabetes mellitus, and hypertension as the independent
      predictors of CAD. CONCLUSIONS: HHcy appears to have a graded effect on the risk
      of CAD as well as the severity and extent of coronary atherosclerosis. Our
      findings support that homozygous genotype of MTHFR is a genetic risk factor for
      CAD. A further study with larger sample size including assessment of vitamin
      status is needed to better clarify the relationship between MTHFR genotypes and
      CAD.

PMID- 18074112
TI  - [Effects of nicotine on neurodevelopment].
AB  - Nicotine exposure during prenatal to adolescent neurodevelopment causes
      morphologic changes in the CNS and persistent alterations of neurotransmission
      systems. Maternal smoking on the one hand and nicotine dependency and attention
      deficit hyperactivity disorder in the offspring on the other are significantly
      associated. There is even evidence that nicotine abuse during adolescence may
      result in deficits of the brain's attentional network. In contrast, any effects
      of nicotine exposure on the development of various psychiatric diseases are still
      unclear. The somatic consequences of smoking and the resulting economic problems
      are already well known, but the effects of nicotine on neurodevelopment are still
      underestimated. More public awareness training and medical education are required
      to avoid nicotine abuse in pregnant women, children, and adolescents.

PMID- 18074113
TI  - [Functional imaging of cognitive processes in Huntington's disease and its
      presymptomatic mutation carriers].
AB  - Cognitive deficits are among the core symptoms of patients with Huntington's
      disease (HD). While impaired attention, visuospatial processing, and memory can
      be observed during early stages of the illness, HD patients exhibit deficits in
      executive function on tests requiring planning, problem solving, and cognitive
      flexibility with progression of the disease. Cognitive dysfunction is already
      present in individuals who carry the HD gene mutation but remain presymptomatic
      for motor and cognitive disturbances. This review provides an overview and a
      discussion of functional neuroimaging findings on cognitive dysfunction in
      patients with HD and presymptomatic HD gene mutation carriers. In HD patients,
      currently available evidence suggests a functional deficit of multiple cortical
      and subcortical regions extending beyond volumetric abnormalities. Early
      dysfunction of lateral prefrontal and cingulate regions has been shown in
      individuals with presymptomatic HD, while compensatory responses of posterior
      brain regions may occur closer to the onset of manifest clinical symptoms. While
      functional neuroimaging techniques may substantially contribute to defining
      neurodegenerative disease phenotypes and to identifying neural biomarkers in
      presymptomatic individuals, the extant data on cognitive function in HD patients
      and HD gene carriers however is sparse and has to be expanded through further
      studies.

PMID- 18074114
TI  - Fine scale genetic and physical mapping using interstitial deletion mutants of
      Lr34 /Yr18: a disease resistance locus effective against multiple pathogens in
      wheat.
AB  - The Lr34/Yr18 locus has contributed to durable, non-race specific resistance
      against leaf rust (Puccinia triticina) and stripe rust (P. striiformis f. sp.
      tritici) in wheat (Triticum aestivum). Lr34/Yr18 also cosegregates with
      resistance to powdery mildew (Pm38) and a leaf tip necrosis phenotype (Ltn1).
      Using a high resolution mapping family from a cross between near-isogenic lines
      in the "Thatcher" background we demonstrated that Lr34/Yr18 also cosegregated
      with stem rust resistance in the field. Lr34/Yr18 probably interacts with
      unlinked genes to provide enhanced stem rust resistance in "Thatcher". In view of
      the relatively low levels of DNA polymorphism reported in the Lr34/Yr18 region,
      gamma irradiation of the single chromosome substitution line,
      Lalbahadur(Parula7D) that carries Lr34/Yr18 was used to generate several mutant
      lines. Characterisation of the mutants revealed a range of highly informative
      genotypes, which included variable size deletions and an overlapping set of
      interstitial deletions. The mutants enabled a large number of wheat EST derived
      markers to be mapped and define a relatively small physical region on chromosome
      7DS that carried Lr34/Yr18. Fine scale genetic mapping confirmed the physical
      mapping and identified a genetic interval of less than 0.5 cM, which contained
      Lr34/Yr18. Both rice and Brachypodium genome sequences provided useful
      information for fine mapping of ESTs in wheat. Gene order was more conserved
      between wheat and Brachypodium than with rice but these smaller grass genomes did
      not reveal sequence information that could be used to identify a candidate gene
      for rust resistance in wheat. We predict that Lr34/Yr18 is located within a large
      insertion in wheat not found at syntenic positions in Brachypodium and rice.

PMID- 18074116
TI  - [Primary osteochondrodysplasias: many forms of manifestation and difficult
      diagnosis].

PMID- 18074115
TI  - A guanylyl cyclase-like gene is associated with Gibberella ear rot resistance in
      maize (Zea mays L.).
AB  - Gibberella ear rot, caused by the fungal pathogen Fusarium graminearum Schwabe,
      is a serious disease of maize (Zea mays L.) grown in northern climates. The
      infected maize grain contains toxins that are very harmful to livestock and
      humans. A maize gene that encodes a putative 267-amino acid guanylyl cyclase-like
      protein (ZmGC1) was characterized and shown to be associated with resistance to
      this disease. The putative ZmGC1 amino acid sequence is 53% identical and 65%
      similar to AtGC1, an Arabidopsis guanylyl cyclase. The Zmgc1 coding sequence is
      nearly identical in a Gibberella ear rot-resistant line (CO387) and a susceptible
      line (CG62) but several nucleotide sequence differences were observed in the UTRs
      and introns of the two alleles. Using a 463 bp probe derived from the CG62 allele
      of Zmgc1 and a recombinant inbred (RI) mapping population developed from a CG62 x
      CO387 cross, six Zmgc1 restriction fragment length polymorphism (RFLP) fragments
      (ER1_1, ER1_2, ER1_3, ER1_4, ER1_5, and ER5_1) were mapped on maize chromosomes
      2, 3, 7, and 8. Markers ER1_1 and ER5_1 on chromosomes 7 and 8, respectively,
      were significantly associated with Gibberella ear rot resistance, each in three
      different environments. The amount of Zmgc1 transcript in ear tissues increased
      more quickly and to a greater extent in the resistant genotype compared to the
      susceptible genotype after inoculation with F. graminearum. Zmgc1 is the first
      guanylyl cyclase gene characterized in maize and the first gene found to be
      associated with Gibberella ear rot resistance in this plant.

PMID- 18074118
TI  - Articular cartilage injury of the posterior lateral tibial plateau associated
      with acute anterior cruciate ligament injury.
AB  - Thirty-nine knees in 39 patients with recent anterior cruciate ligament (ACL)
      rupture (age 14-55 years; with a mean age of 22.8 years) were selected from our
      cases of ACL reconstruction from July 2005 to June 2006, to take part in a study
      on articular cartilage injury of the posterior lateral tibial plateau associated
      with acute ACL injury and on the correlation between bone bruises depicted on MRI
      and cartilage injury of the posterior lateral tibial plateau detected at
      arthroscopic ACL reconstruction. Using preoperative MRI, we evaluated whether
      there were bone bruises or not in the lateral compartment of the knee and divided
      them accordingly into two groups: the bone bruise positive group and the negative
      group. The differences in the proportions of the lateral meniscus (LM) tears and
      the cartilage injuries in the two groups were evaluated using Fisher's exact
      probability test. Thirty-five cases out of 39 arthroscopic ACL reconstructions
      (89.7%) were regarded as bone bruise positive in the lateral compartment and four
      cases (10.3%) were regarded as negative. At arthroscopic ACL reconstruction, 33
      cases (84.6%) had tears in the LM posterior horn, 34 cases (87.2%) had articular
      cartilage injuries in the lateral femoral condyle and 29 cases (74.3%) had
      articular cartilage injuries in the posterior lateral tibial plateau. From 35
      bone bruise positive cases, 32 cases (91.4%) had tears in the LM posterior horn,
      33 cases (94.3%) had articular cartilage injuries in the lateral femoral condyle
      and 28 cases (80%) had articular cartilage injuries in the posterior lateral
      tibial plateau. Of four bone bruise negative cases, one case (25%) had a tear in
      the LM posterior horn, articular cartilage injury of the lateral femoral condyle
      and of the posterior lateral tibial plateau. There was a statistically
      significant correlation between the proportion of bone bruise and cartilage
      injury of the lateral femoral condyle (P = 0.004), that of the posterior lateral
      tibial plateau (P = 0.04) and that of tears in the LM posterior horn (P = 0.008).
      This current study has demonstrated that we need to pay attention to cartilage
      damage of the posterior lateral tibial plateau as well as to posterior horn tears
      in LM, when acute ACL injury is shown. We also have to ensure that we follow the
      long-term progress of cartilage injuries, with the aim of preventing these
      injuries becoming osteoarthritis after ACL reconstruction.

PMID- 18074119
TI  - Diphenyl diselenide supplementation delays the development of N-nitroso-N
      methylurea-induced mammary tumors.
AB  - The effect of dietary diphenyl diselenide (1 ppm) on N-nitroso-N-methylurea (NMU)
      induced mammary carcinogenesis was examined in female Wistar rats. Beginning at 5
      weeks of age, the animals were fed with either control or diphenyl-diselenide
      supplied diets until the end of the study (210 days). At 50 days of age, mammary
      tumor was induced by the administration of three doses of NMU (50 mg/kg body wt,
      intraperitoneally) once a week for 3 weeks. In experimental trials, latency to
      tumor onset was extended in rats fed with diet supplemented with diphenyl
      diselenide (P < 0.05). The incidence and frequency of tumors were significantly
      small in animals supplemented with diphenyl diselenide. However, the multiplicity
      of tumors was not altered by dietary diphenyl diselenide. Diphenyl diselenide
      supplementation also restored superoxide dismutase (SOD) activity and vitamin C
      levels altered in the NMU group (P < 0.05). Our results suggest that diphenyl
      diselenide can be considered a chemopreventive agent, even when supplemented at a
      relatively low concentration.

PMID- 18074120
TI  - Differential modulation of K(+)-evoked (3)H-neurotransmitter release from human
      neocortex by gabapentin and pregabalin.
AB  - Anticonvulsant, analgesic, and anxiolytic effects have been observed both in
      preclinical and clinical studies with gabapentin (GBP) and pregabalin (PGB).
      These drugs appear to act by binding to the alpha(2)delta subunit of voltage
      sensitive Ca(2+) channels (VSCC), resulting in the inhibition of neurotransmitter
      release. In this study, we examined the effects of GBP and PGB (mostly 100
      microM, corresponding to relatively high preclinical/clinical plasma levels) on
      the release of neurotransmitters in human neocortical slices. These slices were
      prelabeled with (3)H-dopamine ((3)H-DA), (3)H-choline (to release (3)H
      acetylcholine ((3)H-ACh)), (3)H-noradrenaline ((3)H-NA), and (3)H-serotonin ((3)H
      5-HT), and stimulated twice in superfusion experiments by elevation of
      extracellular K(+) in the presence and absence of GBP and PGB. The alpha(2)delta
      ligands produced significant inhibitions of K(+)-evoked (3)H-ACh, (3)H-NA, and
      (3)H-5-HT release between 22% and 56% without affecting (3)H-DA release. Neither
      drug reduced (3)H-NA release in the presence of L: -isoleucine, a putative
      alpha(2)delta antagonist. Interestingly, this antagonism did not occur using the
      enantiomer, D: -isoleucine. These results suggest that GBP and PGB are not
      general inhibitors of VSCC and neurotransmitter release. Such alpha(2)delta
      ligands appear to be selective modulators of the release of certain, but not all,
      neurotransmitters. This differential modulation of neurotransmission presumably
      contributes to their clinical profile.

PMID- 18074121
TI  - In vivo characterization of muscarinic receptors in peripheral tissues:
      evaluation of bladder selectivity of anticholinergic agents to treat overactive
      bladder.
AB  - The present study was undertaken to characterize in vivo muscarinic receptors in
      peripheral tissues (urinary bladder, submaxillary gland, colon, stomach, heart)
      of mice, and further to evaluate bladder-selectivity of anticholinergic agents to
      treat overactive bladder. Following i.v. injection of [3H]QNB in mice, the
      radioactivity in peripheral tissues was exclusively detected as the unchanged
      form. The in vivo specific [3H]QNB binding in particulate fraction of tissue
      homogenates of mice showed a pharmacological specificity which characterized
      muscarinic receptors. Binding parameters (Kd and Bmax) for in vivo specific
      [3H]QNB binding differed between mouse tissues. Oral administration of oxybutynin
      attenuated significantly in vivo specific [3H]QNB binding in all tissues of mice.
      From ratios of AUCurinary bladder/AUCother tissues of time-dependent muscarinic
      receptor occupancy, oral oxybutynin has been shown to exert little urinary
      bladder selectivity. Following oral administration of propiverine, there was a
      significant reduction of in vivo specific [3H]QNB binding in the urinary bladder,
      colon and submaxillary gland, but not in the stomach and heart. From the ratios
      of AUCurinary bladder to AUCsubmaxillary gland or AUCheart, it has been shown
      that oral propiverine exerts higher selectivity to muscarinic receptors in the
      urinary bladder than in the submaxillary gland and heart. Similarly, tolterodine
      displayed high selectivity to muscarinic receptors in the urinary bladder than in
      the submaxillary gland. Thus, the present study has demonstrated that [3H]QNB may
      be a useful ligand for in vivo characterization of muscarinic receptor binding of
      anticholinergic agents to treat overactive bladder. Propiverine and tolterodine
      have exhibited in vivo selectivity of muscarinic receptor in the mouse urinary
      bladder rather than in the submaxillary gland, and such receptor binding
      specificity may be the reason of lower incidence of dry mouth.

PMID- 18074123
TI  - Solution to "Doctrine of Signatures" challenge.

PMID- 18074122
TI  - The relationship between core body temperature and 3,4
      methylenedioxymethamphetamine metabolism in rats: implications for neurotoxicity.
AB  - RATIONALE: A close relationship appears to exist between 3,4
      methylenedioxymethamphetamine (MDMA)-induced changes in core body temperature and
      long-term serotonin (5-HT) loss. OBJECTIVE: We investigated whether changes in
      core body temperature affect MDMA metabolism. MATERIALS AND METHODS: Male Wistar
      rats were treated with MDMA at ambient temperatures of 15, 21.5, or 30 degrees C
      to prevent or exacerbate MDMA-induced hyperthermia. Plasma concentrations of MDMA
      and its main metabolites were determined for 6 h. Seven days later, animals were
      killed and brain indole content was measured. RESULTS: The administration of MDMA
      at 15 degrees C blocked the hyperthermic response and long-term 5-HT depletion
      found in rats treated at 21.5 degrees C. At 15 degrees C, plasma concentrations
      of MDMA were significantly increased, whereas those of three of its main
      metabolites were reduced when compared to rats treated at 21.5 degrees C. By
      contrast, hyperthermia and indole deficits were exacerbated in rats treated at 30
      degrees C. Noteworthy, plasma concentrations of MDMA metabolites were greatly
      enhanced in these animals. Instrastriatal perfusion of MDMA (100 microM for 5 h
      at 21 degrees C) did not potentiate the long-term depletion of 5-HT after
      systemic MDMA. Furthermore, interfering in MDMA metabolism using the catechol-O
      methyltransferase inhibitor entacapone potentiated the neurotoxicity of MDMA,
      indicating that metabolites that are substrates for this enzyme may contribute to
      neurotoxicity. CONCLUSIONS: This is the first report showing a direct
      relationship between core body temperature and MDMA metabolism. This finding has
      implications on both the temperature dependence of the mechanism of MDMA
      neurotoxicity and human use, as hyperthermia is often associated with MDMA use in
      humans.

PMID- 18074124
TI  - Reduced intracortical inhibition during the foreperiod of a warned reaction time
      task.
AB  - Reaction time (RT) is shortened when the response signal is preceded by a warning
      signal, a finding that has been attributed to response preparation during the
      foreperiod between the warning and response signals. Research suggests an
      increased excitability of cortical movement representations associated with
      response preparation during the foreperiod of a warned RT task (Davranche et al.
      in Eur J Neurosci 25:3766-3774, 2007). However when the foreperiod duration is
      short and constant, the motor evoked potential (MEP) amplitude elicited by
      transcranial magnetic stimulation (TMS) during the foreperiod is suppressed
      (Touge et al. in Clin Neurophysiol 111:1216-1226, 1998), suggesting a competing
      inhibitory process. Three experiments measured MEP amplitude and intracortical
      inhibition during the foreperiod of a warned RT task in which the response was a
      flexion of the right index finger. Experiments 1 and 2 measured short-interval
      intracortical inhibition (SICI) with paired TMS pulses separated by inter
      stimulus intervals (ISIs) of 3 (SICI(3)) and 1.5 ms (SICI(1.5)), respectively.
      Experiment 3 measured long-interval intracortical inhibition (LICI) with paired
      TMS pulses with an ISI of 100 ms (LICI(100)). In all experiments MEP amplitude
      was smaller in the warned condition than in the unwarned condition. There was
      less SICI(3) in the warned condition than in the unwarned condition (Experiment
      1) whereas SICI(1.5) was similar in both conditions (Experiment 2). There was
      less LICI(100) in the warned condition than in the unwarned condition (Experiment
      3). The intracortical inhibitory processes measured here cannot explain the
      suppression of MEP amplitude in the warned condition. We propose that the
      suppression of MEP amplitude is the result of an inhibitory mechanism, which acts
      on primary motor cortex to prevent premature response during the foreperiod.

PMID- 18074125
TI  - Evaluation of cystine transport in cultured human kidney cells and establishment
      of cystinuria type I phenotype by antisense technology.
AB  - Cystinuria is a rare hereditary disease resulting in recurrent stone formation
      and the need for repeated invasive interventions. So far, two responsible genes
      have been identified which encode the two transporters, rBAT and b(0,+)AT forming
      a heterodimer to transport cystine in proximal tubular cells (PTC) and whose
      defect results in increased excretion of cystine. A human cell line mimicing the
      phenotype of cystinuria in vitro is yet to be developed. Human kidney (HK)-2 is a
      PTC line derived from normal HK. After determining the presence of rBAT gene by
      RT-PCR and Western blot analysis, radioactively labeled cystine (S(35)) was used
      to evaluate the functional presence of the amino acid transport in HK-2 cells
      when cultured in vitro. To achieve a cystinuria type I phenotype in HK-2 cells,
      the rBAT gene was silenced using antisense oligonucleotides complimentary to
      human rBAT mRNA. The reduced transport activity of cystine was then determined by
      radiolabeled cystine uptake measurements. RT-PCR and Western blot confirmed the
      expression of the rBAT gene in HK-2 cells. Considerable transport of the radio
      labeled cystine was observed in HK-2 cells and was linearly dependent on the
      incubation time with the amino acid. The cystine transport in rBAT knockdown
      cells after incubation with antisense oligonucleotides was significantly lower
      compared to control (0.76 vs. 0.98%; P=0.0008), proving a transient knock-down of
      the rBAT gene. This study demonstrates the presence of the b(0,+) amino acid
      transport system in human proximal tubular HK-2 cells when cultured in vitro.
      Inhibition of this transport system is possible by using antisense technology. A
      permanent inhibition of the cystine transport, based on our model, would be
      useful for the development and evaluation gene therapeutic approaches.

PMID- 18074126
TI  - Requirements for accurately diagnosing chronic partial upper urinary tract
      obstruction in children with hydronephrosis.
AB  - Successful management of hydronephrosis in the newborn requires early accurate
      diagnosis to identify or exclude ureteropelvic junction obstruction. However, the
      presence of hydronephrosis does not define obstruction and displays unique
      behavior in the newborn. The hydronephrotic kidney usually has nearly normal
      differential renal function at birth, has not been subjected to progressive
      dilation and except for pelvocaliectasis does not often show signs of high-grade
      obstruction. Furthermore, severe hydronephrosis resolves spontaneously in more
      than 65% of newborns with differential renal function stable or improving. The
      diagnosis of obstruction in newborn hydronephrosis is challenging because the
      currently available diagnostic tests, ultrasonography and diuretic renography
      have demonstrated inaccuracy in diagnosing obstruction and predicting which
      hydronephrotic kidney will undergo deterioration if untreated. Accurate diagnosis
      of obstruction is possible but it requires an understanding of the uniqueness of
      both the pathophysiology of obstruction and the biology of the kidney and renal
      collecting system in this age group. We examine here the requirements for making
      an accurate diagnosis of obstruction in the young child with hydronephrosis.

PMID- 18074127
TI  - Modeling systemic and renal gadolinium chelate transport with MRI.
AB  - The advent of modern MRI scanners and computer equipment permits the rapid
      sequential collection of images of gadolinium chelate (Gd) transit through the
      kidney. The excellent spatial and temporal (0.9 s) resolution permits analyzing
      the shape of the recovered curves with a sophisticated model that includes both
      space and time. The purpose of this manuscript is to present such a mathematical
      model. By building into the model significant physical processes that contribute
      to the shape of the measured curve, quantitative values can be assigned to
      important parameters. In this work, quantitative values are determined for blood
      dispersion through the cardio-pulmonary system, systemic clearance rate of Gd,
      blood flow into each kidney, blood transit time in each kidney, the extraction
      rate of Gd across the capillary membrane, interstitial distribution volume, and
      the GFR for each kidney.

PMID- 18074129
TI  - Real-time PCR determination of rRNA gene copy number: absolute and relative
      quantification assays with Escherichia coli.
AB  - Real-time polymerase chain reaction (PCR)-based methodology for the determination
      of rRNA gene (rrn) copy number was introduced and demonstrated. Both absolute and
      relative quantifications were tested with Escherichia coli. The separate
      detection of rRNA gene and chromosomal DNA was achieved using two primer sets,
      specific for 16S rRNA gene and for D-1-deoxyxylulose 5-phosphate synthase gene
      (dxs), respectively. As dxs is a single-copy gene of E. coli chromosomal DNA, the
      rrn copy number can be determined as the copy ratio of rrn to dxs. This
      methodology was successfully applied to determine the rrn copy number in E. coli
      cells. The results from absolute and relative quantifications were identical and
      highly reproducible with coefficient of variation (CV) values of 1.8-4.6%. The
      estimated rrn copy numbers also corresponded to the previously reported value in
      E. coli (i.e., 7), indicating that the results were reliable. The methodology
      introduced in this study is faster and cost-effective without safety problems
      compared to the traditionally used Southern blot analysis. The fundamentals in
      our methodology would be applicable to any microorganism, as long as having the
      sequence information of the rRNA gene and another chromosomal gene with a known
      copy number.

PMID- 18074130
TI  - The effects of bioprocess parameters on extracellular proteases in a recombinant
      Aspergillus niger B1-D.
AB  - Although host proteases are often considered to have a negative impact upon
      heterologous protein production by filamentous fungi, relatively little is known
      about the pattern of their appearance in recombinant fungal bioprocesses. In the
      present study, we investigated extracellular proteases from a filamentous fungus,
      Aspergillus niger B1-D, genetically modified to secrete hen egg white lysozyme
      (HEWL). Our findings indicate that extracellular protease activity is only
      detected after the carbon source is completely utilised in batch cultures. The
      proteases are predominantly acid proteases and have optimal temperature for
      activity at around 45 degrees C. Their activity could be partially inhibited by
      protease inhibitors, indicating the existence of at least four kinds of proteases
      in these culture fluids, aspartic-, serine-, cysteine-, and metallo-proteases.
      Oxygen enrichment does not have any noticeable effects on extracellular protease
      activity except that the onset of protease activity appears earlier in oxygen
      enrichment runs. Oxygen enrichment stimulates HEWL production substantially, and
      we propose that it is related to fungal morphology. Thermal stress imposed by
      raising process temperature (from 25 to 30 and 35 degrees C) in early exponential
      phase, led to appearance of protease activity in the medium following the heat
      shock. Continued cultivation at high temperatures significantly reduced HEWL
      production, which was associated with increased activity of the extracellular
      proteases in these cultures.

PMID- 18074131
TI  - Simultaneous biodegradation of creosote-polycyclic aromatic hydrocarbons by a
      pyrene-degrading Mycobacterium.
AB  - When incubated with a creosote-polycyclic aromatic hydrocarbons (PAHs) mixture,
      the pyrene-degrading strain Mycobacterium sp. AP1 acted on three- and four-ring
      components, causing the simultaneous depletion of 25% of the total PAHs in 30
      days. The kinetics of disappearance of individual PAHs was consistent with
      differences in aqueous solubility. During the incubation, a number of acid
      metabolites indicative of distinctive reactions carried out by high-molecular
      weight PAH-degrading mycobacteria accumulated in the medium. Most of these
      metabolites were dicarboxylic aromatic acids formed as a result of the
      utilization of growth substrates (phenanthrene, pyrene, or fluoranthene) by
      multibranched pathways including meta- and ortho-ring-cleavage reactions:
      phthalic acid, naphthalene-1,8-dicarboxylic acid, phenanthrene-4,5-dicarboxylic
      acid, diphenic acid, Z-9-carboxymethylenefluorene-1-carboxylic acid, and 6,6'
      dihydroxy-2,2'-biphenyl dicarboxylic acid. Others were dead-end products
      resulting from cometabolic oxidations on nongrowth substrates (fluorene meta
      cleavage product). These results contribute to the general knowledge of the
      biochemical processes that determine the fate of the individual components of PAH
      mixtures in polluted soils. The identification of the partially oxidized
      compounds will facilitate to develop analytical methods to determine their
      potential formation and accumulation in contaminated sites.

PMID- 18074132
TI  - Vinorelbine and gemcitabine as salvage treatment in advanced and very poor
      prognosis non-Hodgkin's lymphoma patients.

PMID- 18074133
TI  - Daunorubicin, cytarabine and fludarabine (DAF) for remission induction in
      relapsed or refractory acute myeloid leukemia. Evaluation of safety, tolerance
      and early outcome--Polish Adult Leukemia Group (PALG) pilot study.
AB  - In 1992-1993, synergistic interaction of ribonucleotide reductase inhibitors
      (fludarabine, cladribine) and cytarabine (Ara-C) increasing Ara-CTP concentration
      in myeloblasts was proved. Based on these findings and encouraging results of the
      addition of cladribine to standard daunorubicin+Ara-C induction regimen (DAC) in
      acute myeloid leukemia (AML), the Polish Adult Leukemia Group (PALG) conducted a
      pilot study on the administration of cytarabine, daunorubicin, and fludarabine
      (DAF) as a reinduction treatment of AML to assess tolerance, toxicity, and early
      outcome. The DAF regimen consisted of daunorubicine 60 mg m(-2) day(-1) iv on
      days 1-3 and fludarabine 25 mg m(-2) day(-1) iv on days 1-5 given before
      cytarabine 200 mg m(-2) day(-1) in ci on days 1-7. Thirty-four AML patients with
      median age 39, 24% relapsed and 76% refractory, were included into the study
      between September 2003 and August 2004. Achieved response rate in the whole study
      population was 56%; n = 16 patients with complete remission (CR), and n = 3
      patients with partial remission (PR). Fifteen of 16 patients achieved CR after
      the first course of therapy. Only 9% of total population died before the
      assessment of remission. All patients developed severe neutropenia. Serious
      infections were observed in 47% of the cases. Severe thrombocytopenia was
      observed in 72% of the patients. All patients required substitution of platelet
      concentrates (median 4), and PRBC (median 5). Severe alopecia, mucositis,
      vomiting were of low frequency. Liver, kidney, or circulatory failure, diarrhea,
      or polyneuropathy were not observed. The probability of overall survival (OS) for
      1 year for the whole study population (34 patients) and the group of 16 patients
      in CR was: 44% (95% confidence interval [CI] 36-52%) and 69% (95% CI 55-83%),
      respectively. The probability of leukemia-free survival (LFS) for 1 year was 38%
      (95% CI 22-54%). Summarizing, DAF regimen used as the induction therapy in
      relapsed/refractory AML was well tolerated with acceptable toxicity and early
      efficacy.

PMID- 18074134
TI  - Antibody to a high-prevalence blood group antigen Ata associated with Sjogren's
      syndrome.

PMID- 18074136
TI  - Epidural hematoma mimicking transverse myelitis in a patient with primary
      antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease, and its most critical
      pathologic process is thrombosis, which may explain most of the clinical
      features. Acute management of thrombosis involves immediate anticoagulation.
      Acute proximal venous thrombosis can be managed with thrombolytic therapy to
      reduce the long-term complications of the postthrombotic syndrome (pain,
      swelling, skin discoloration, or ulceration) and perform recanalization of
      occluded vessels. However, thrombolytic therapies are associated with high risks
      of bleeding. To our knowledge, this is the first report of epidural hematoma
      mimicking transverse myelitis after catheter-directed thrombolysis in a patient
      with primary APS. A 42-year-old male was admitted with sudden onset pain and
      swelling on left lower extremity. Venography demonstrated multiple thrombi on
      superficial femoral vein, common femoral vein, common iliac vein, and external
      iliac vein. Laboratory tests indicated the presence of IgM anticardiolipin
      antibody. He was diagnosed with primary APS with multiple venous thrombi. He was
      treated with urokinase (200,000/h) as thrombolytic therapy. After 1 day, he
      complained both leg weakness and urinary dysfunction. T1- and T2-weighted
      magnetic resonance images of spine showed about 8 cm-sized mass, suggesting
      hematoma on the posterior epidural space at thoracolumbar area. Despite the
      successful evacuation of hematoma, neurologic symptoms persisted and he is now
      receiving aspirin, warfarin, and physical therapy.

PMID- 18074135
TI  - BRCA1 modulates sensitivity to 5F-203 by regulating xenobiotic stress-inducible
      protein levels and EROD activity.
AB  - PURPOSE: We have investigated the effects of BRCA1 over-expression and knockdown
      on 5F-203-induced gene expression and cytotoxicity in human breast cancer cells.
      5F-203 is a chemotherapeutic prodrug that both induces a p450 enzyme, CYP1A1, and
      is metabolically activated by CYP1A1. METHODS: We used several molecular
      biological techniques to confirm our findings. BRCA1 regulates sensitivity to 5F
      203 by regulating the expression of CYP1A1 mRNA and its EROD activity. XRE-Luc
      reporter assays, semi-quantitative RT-PCR, Western blot analysis, EROD activity
      measurements, gene knockdown and MTT cell survival assays were used for this
      study. RESULTS: Our results show that the ability of 5F-203 treatments to
      increase CYP1A1 mRNA level and CYP1A1 enzymatic activity (EROD activity) are
      affected by BRCA1 protein levels. In addition, the ability of 5F-203 treatments
      to induce proteins, P53 and P53 target genes such as P21, is significantly
      decreased in BRCA1 knockdown cells, suggesting that BRCA1-related effects could
      at least partially explain why BRCA1 knockdown increases resistance to 5F-203
      mediated cytotoxicity. We also observed altered expression of the two major
      transcription factors (AhR and ARNT) that affect CYP1A1 expression when BRCA1
      protein levels are altered. CONCLUSION: BRCA1 is an important protein, which
      affects 5F-203-mediated cytotoxicity. Our findings are potentially clinically
      significant; they suggest that those patients most likely to respond to this new
      prodrug will have tumors containing normal amounts of BRCA1.

PMID- 18074137
TI  - Definition of disease duration in ankylosing spondylitis.
AB  - Two definitions of the "disease duration" of ankylosing spondylitis (AS) have
      been used in the literature: (1) duration since first symptoms connected with AS
      and (2) duration since diagnosis of AS. To investigate how useful these
      definitions are for research, we reinvestigated the data of four surveys
      completed by patients with AS in the years since 1996. We found that the majority
      of the patients remembered the age at first symptoms with an accuracy of <or=1
      year, and that the difference between both definitions (the delay in diagnosis)
      was between 9.8 and 10.4 years on average, with extreme values of more than 30
      years being not very seldom. Because the error made using the duration since
      diagnosis as "disease duration" is much larger than the inaccuracy taken into
      account using the duration since first symptoms, only the duration since first
      symptoms connected with AS should be used as definition for the term "disease
      duration" of AS.

PMID- 18074138
TI  - The rice pathogen-related protein 10 (JIOsPR10) is induced by abiotic and biotic
      stresses and exhibits ribonuclease activity.
AB  - We previously reported that rice blast fungus or jasmonic acid induced the
      expression of rice pathogenesis-related class 10 (JIOsPR10) proteins (Kim et al.
      2003, 2004). However, no further studies have been carried out to examine the
      expression, localization, and enzymatic activity of this protein in either
      developmental tissues or in tissues under abiotic stress conditions. In this
      study, rice JIOsPR10 was examined by Western blot analysis, immunolocalization,
      and biochemical assays. Western blots revealed that the JIOsPR10 protein was
      expressed in developmental tissues, including in flower and root. The protein was
      also expressed under abiotic stresses, such as occurs during senescence and
      wounding. Using immunohistochemical techniques, we determined that expression of
      JIOsPR10 was localized to the palea of flower, in the exodermis, and inner part
      of the endodermis of the root. In senescencing tissues of leaf and coleoptiles,
      its expression was localized in vascular bundles. The RNase activity using
      JIOsPR10 recombinant protein was determined and abolished after treatment with
      DTT in a native in-gel assay. To test this, we created JIOsPR10 mutant proteins
      containing serine substitutions of amino acids C81S, C83S, or both and examined
      their RNase activities. The activity of the C83S mutant was decreased in the
      agarose gel assay compared to the wild type. Taken together, we hypothesize that
      the JIOsPR10 protein possesses RNase activity that is sensitive to DTT,
      suggesting the importance of the disulfide bonding between cysteine residues and
      that it might play a role in constitutive self-defense mechanisms in plants
      against biotic and abiotic stresses.

PMID- 18074139
TI  - Analysis of genetic diversity through AFLP, SAMPL, ISSR and RAPD markers in
      Tribulus terrestris, a medicinal herb.
AB  - Tribulus terrestris is well known for its medicinal importance in curing urino
      genital disorders. Amplified fragment length polymorphism (AFLP), selective
      amplification of microsatellite polymorphic loci (SAMPL), inter-simple sequence
      repeat (ISSR) and randomly amplified polymorphic DNA (RAPD) markers were used for
      the first time for the detection of genetic polymorphism in this medicinal herb
      from samples collected from various geographical regions of India. Six assays
      each of AFLP and SAMPL markers and 21 each of ISSR and RAPD markers were
      utilized. AFLP yielded 500 scorable amplified products, of which 82.9% were
      polymorphic. SAMPL primers amplified 488 bands, 462 being polymorphic (94.7%).
      The range of amplified bands was 66 [(TC)(8)G + M-CAG] to 98 [(CA)(6)AG + M-CAC]
      and the percentage polymorphism, 89.9 [from (CT)(4)C (AC)(4)A + M-CTG] to 100
      [from (GACA)(4) + M-CTA]. The ISSR primers amplified 239 bands of 0.4-2.5 kb,
      73.6% showed polymorphism. The amplified products ranged from 5 to 16 and the
      percentage polymorphism 40-100. RAPD assays produced 276 bands, of which 163 were
      polymorphic (59%). Mantel test employed for detection of goodness of fit
      established cophenetic correlation values above 0.9 for all the four marker
      systems. The dendrograms and PCA plots derived from the binary data matrices of
      the four marker systems are highly concordant. High bootstrap values were
      obtained at major nodes of phenograms through WINBOOT software. The relative
      efficiency of the four molecular marker systems calculated on the basis of
      multiplex ratio, marker index and average heterozygosity revealed SAMPL to be the
      best. Distinct DNA fingerprinting profile, unique to every geographical region
      could be obtained with all the four molecular marker systems. Clustering can be a
      good indicator for clear separation of genotypes from different regions in well
      defined groups that are supported by high bootstrap values.

PMID- 18074140
TI  - Johann Anton von Mikulicz-Radecki (1850-1905)--a pioneer of gastroscopy and
      modern surgery: his credit to urology.
AB  - The author presents the life and achievements of Johann von Mikulicz-Radecki and
      his contribution to European and world surgery. Mikulicz was born in Czernowitz,
      then a part of the Austro-Hungarian Empire. He was educated in numerous Austrian
      schools and graduated at Vienna University in 1875. In 1880 he became surgeon and
      lecturer (Docent) in the famous Billroth's School of surgery in Vienna. His
      scientific and clinical activity as assistant in Vienna and full professor in
      Cracow, Koenigsberg and Breslau resulted in 232 publications. He described many
      at that time novel surgical methods. He constructed the esophagogastroscope,
      scoliometer, peritoneal clamp and many other surgical devices. He organized the
      first in the world aseptical operation theatre in Breslau. He adopted hand
      disinfection, cotton and rubber gloves, mask, cup and general and local
      anaesthesia. Besides his many contributions to general, gastrointestinal and
      thoracic surgery Mikulicz devoted himself also to urological surgery. He
      performed ureterointestinal anastomosis and the first ileocystoplasty on a
      patient suffering from extrophy of the bladder. He died prematurely at the age of
      55 in Breslau.

PMID- 18074141
TI  - Influence of sound pressure level on the processing of amplitude modulations by
      auditory neurons of the locust.
AB  - Typical features of natural sounds are amplitude changes at different time
      scales. In many species, amplitude modulations constitute decisive cues to
      recognize communication signals. Since these signals should be recognizable over
      a broad intensity range, we investigated how the encoding of amplitude
      modulations by auditory neurons depends on sound pressure level. Identified
      neurons that represent different processing stages in the locusts' auditory
      pathway were stimulated with sinusoidal modulations of a broad band noise
      carrier, at different intensities, and characteristic parameters of modulation
      transfer functions (MTFs) were determined. The corner frequencies of temporal
      MTFs turned out to be independent of intensity for all neurons except one.
      Furthermore, for none of the neurons investigated corner frequencies were
      significantly correlated with spike rate, indicating a remarkable intensity
      invariance of the upper limits of temporal resolution. The shape of the tMTFs
      changed with increasing intensity from a low-pass to a band-pass for receptors
      and local neurons, while no consistent change was observed for ascending neurons.
      The best modulation frequency depended on intensity and spike rate, especially
      for receptors and local neurons. Remarkably, the adaptation state of some neurons
      turned out to be independent of the spike rate during the modulation part of the
      stimulus.

PMID- 18074142
TI  - Aggregation protects flexible-shelled reptile eggs from severe hydric stress.
AB  - Many reptiles lay eggs with flexible shells that can progressively lose water
      until lethal dehydration under dry soil conditions. The number of eggs that
      develop together may influence the water exchange in the nest. We hypothesise
      that egg aggregation could reduce water lost under dry conditions. We exposed
      aggregated and isolated eggs to severe hydric stress followed by a period of
      rehydration. Hydric stress caused a general loss of water in common chameleon
      eggs. Initial egg mass did not affect survival but eggs that had lost more water
      had higher mortality and produced smaller hatchlings. Mass loss was higher and
      even lethal for isolated Chamaeleo chameleon eggs. However, aggregated eggs lost
      less water and most survived this period. After hydric stress, all surviving eggs
      gained mass via water absorption, and aggregation negatively affected water
      uptake. Isolated eggs hatched at smaller sizes than aggregated eggs. Aggregation
      also favoured hatching synchrony. Large clutches may favour hatching success of
      terrestrial flexible-shelled eggs incubated under severe drought conditions.

PMID- 18074143
TI  - The proximal airway of the bat Tadarida brasiliensis: a minimum entropy
      production design.
AB  - The bronchial tree of most mammalian lungs is a good example of an efficient
      distribution system whose geometry and dimensions of branched structures are
      important factors in determining the efficiency of respiration. Small and flying
      endothermic animals have high-energy requirements, requiring morphological and
      physiological adaptations to reduce energy loss. Here we show that Tadarida
      brasiliensis, a nocturnal small bat whose energy requirements are exacerbated by
      this small size and by their frequent exposure to high altitude, has a different
      morphology in the proximal airway, sustained by a wider trachea and better
      scaling factors, than other non-flying mammals. This design allows a great
      decrease of the volume specific resistance of the proximal airway and in
      consequence a very low entropy production during breathing, approximately 1/18 of
      that expected for a non-flying mammals of similar body size.

PMID- 18074144
TI  - Endoscopic fenestration of the third ventricle in the reverse direction.
AB  - INTRODUCTION: A case of safely treated parasellar cyst by endoscopic fenestration
      of the third ventricular floor from outside of the ventricle to establish
      communications between the cyst and the ventricle is reported. MATERIALS AND
      METHODS: During the endoscopic procedures, the anterior commissure and the
      foramina of Monro could be clearly observed using this approach. CONCLUSION: In
      treating parasellar cysts with thick walls, endoscopic fenestration of the third
      ventricular floor in the reverse direction, i.e., from inside of the cyst, should
      be considered.

PMID- 18074145
TI  - Infantile myofibromatosis.
AB  - Despite being the most common fibrous tumour of infancy, infantile
      myofibromatosis is still sufficiently rare for the diagnosis not to be apparent
      to many clinicians. We present the data from the 12 cases seen in our institute
      over the last 14 years and highlight three cases, the first a "typical" case,
      then a retroperitoneal myofibroma that presented with duodenal obstruction and
      finally one that presented as an isolated scrotal mass. We have also reviewed the
      literature on the subject.

PMID- 18074146
TI  - Comparison of cardiac output determined by different rebreathing methods at rest
      and at peak exercise.
AB  - Several rebreathing methods are available for cardiac output (Q (T)) measurement.
      The aims of this study were threefold: first, to compare values for resting Q (T)
      produced by the equilibrium-CO(2), exponential-CO(2) and inert gas-N(2)O
      rebreathing methods and, second, to evaluate the reproducibility of these three
      methods at rest. The third aim was to assess the agreement between estimates of
      peak exercise Q (T) derived from the exponential and inert gas rebreathing
      methods. A total of 18 healthy subjects visited the exercise laboratory on
      different days. Repeated measures of Q (T), measured in a seated position, were
      separated by a 5 min rest period. Twelve participants performed an incremental
      exercise test to determine peak oxygen consumption. Two more exercise tests were
      used to measure Q (T) at peak exercise using the exponential and inert gas
      rebreathing methods. The exponential method produced significantly higher
      estimates at rest (averaging 10.9 l min(-1)) compared with the equilibrium method
      (averaging 6.6 l min(-1)) and the inert gas rebreathing method (averaging 5.1 l
      min(-1); P < 0.01). All methods were highly reproducible with the exponential
      method having the largest coefficient of variation (5.3%). At peak exercise,
      there were non-significant differences between the exponential and inert gas
      rebreathing methods (P = 0.14). The limits of agreement were -0.49 to 0.79 l min(
      1). Due to the ability to evaluate the degree of gas mixing and to estimate intra
      pulmonary shunt, we believe that the inert gas rebreathing method has the
      potential to measure Q (T) more precisely than either of the CO(2) rebreathing
      methods used in this study. At peak exercise, the exponential and inert gas
      rebreathing methods both showed acceptable limits of agreement.

PMID- 18074147
TI  - Cooperation in self-organizing map networks enhances information transmission in
      the presence of input background activity.
AB  - The self-organizing map (SOM) algorithm produces artificial neural maps by
      simulating competition and cooperation among neurons. We study the consequences
      of input background activity on simulated self-organization, using the SOM, of
      the retinotopic map in the superior colliculus. The colliculus not only
      represents its inputs but also uses them to localize saccadic targets. Using the
      colliculus as a test-bed enables us to quantify the results of self- organization
      both descriptively, in terms of input-output mutual information, and
      functionally, in terms of the probability of error (expected distortion) in
      localizing targets. We find that mutual information is low, and distortion is
      high, when the SOM operates in the presence of input background activity but
      without the cooperative component (no neighbor training). Cooperation (training
      neighbors) greatly increases mutual information and greatly decreases expected
      distortion. Our simulation results extend theoretical work suggesting that
      cooperative mechanisms are needed to increase the information content of neural
      representations. They also identify input background activity as a factor
      affecting the self-organization of information-transmitting channels in the
      nervous system.

PMID- 18074148
TI  - Evolution of follistatin in teleosts revealed through phylogenetic, genomic and
      expression analyses.
AB  - Follistatin (Fst) inhibits transforming growth factor-beta (TGF-B) proteins and
      is a known regulator of amniote myogenesis. Here, we used phylogenetic, genomic
      and experimental approaches to study its evolution in teleosts. Phylogenetic
      analyses suggested that one fst gene (fst1) is common to euteleosts, but a second
      gene (fst2) is conserved specifically within the Ostariophysi. Zebrafish fst1/2
      respectively appear on chromosomes 5 and 10 in two genomic regions, each with
      conserved synteny to a single region in tetrapods. Interestingly, other teleosts
      have two corresponding chromosomal regions with a similar repertoire of
      paralogues. Phylogenetic reconstruction clustered these gene duplicates into two
      sister clades branching from tetrapod sequences. We suggest that an ancestral fst
      containing chromosome was duplicated during the teleost whole genome duplication,
      but that fst2 was lost in lineages external to the Ostariophysi. We show that
      Fst1 of teleosts/mammals has evolved under strong purifying selection, but the N
      terminal of Fst2 may have evolved under positive selection. Furthermore, the
      tissue-specific expression of zebrafish fst2 was restricted to fewer tissues
      compared to its paralogue and the single fst1 orthologue of Atlantic salmon
      (Salmo salar). Zebrafish fst1/2 may have subfunctionalized relative to non
      duplicated vertebrate lineages, as several regions in the fst promoter of
      tetrapods were conserved with one paralogue, but not both. Finally, we examined
      the embryonic expression of fst1 in a teleost outside the Ostariophysi (Atlantic
      salmon). During segmentation, fst1 was expressed in the anterior somite
      compartment but was excluded from muscle progenitors that strongly expressed
      myogenic regulatory factors (MRFs). Later, fst1 was expressed in myogenic
      progenitors of the pectoral fin buds and also within the pax7(+) cell layer
      external to the myotome.

PMID- 18074149
TI  - Randomised trial of oral versus sequential intravenous/oral cephalosporins in
      children with pyelonephritis.
AB  - The hypothesis was tested that oral antibiotic treatment in children with acute
      pyelonephritis and scintigraphy-documented lesions is equally as efficacious as
      sequential intravenous/oral therapy with respect to the incidence of renal
      scarring. A randomised multi-centre trial was conducted in 365 children aged 6
      months to 16 years with bacterial growth in cultures from urine collected by
      catheter. The children were assigned to receive either oral ceftibuten (9 mg/kg
      once daily) for 14 days or intravenous ceftriaxone (50 mg/kg once daily) for 3
      days followed by oral ceftibuten for 11 days. Only patients with lesions detected
      on acute-phase dimercaptosuccinic acid (DMSA) scintigraphy underwent follow-up
      scintigraphy. Efficacy was evaluated by the rate of renal scarring after 6 months
      on follow-up scintigraphy. Of 219 children with lesions on acute-phase
      scintigraphy, 152 completed the study; 80 (72 females, median age 2.2 years) were
      given ceftibuten and 72 (62 females, median age 1.6 years) were given
      ceftriaxone/ceftibuten. Patients in the intravenous/oral group had significantly
      higher C-reactive protein (CRP) concentrations at baseline and larger lesion(s)
      on acute-phase scintigraphy. Follow-up scintigraphy showed renal scarring in
      21/80 children treated with ceftibuten and 33/72 with ceftriaxone/ceftibuten (p =
      0.01). However, after adjustment for the confounding variables (CRP and size of
      acute-phase lesion), no significant difference was observed for renal scarring
      between the two groups (p = 0.2). Renal scarring correlated with the extent of
      the acute-phase lesion (r = 0.60, p < 0.0001) and the grade of vesico-ureteric
      reflux (r = 0.31, p = 0.03), and was more frequent in refluxing renal units (p =
      0.04). The majority of patients, i.e. 44 in the oral group and 47 in the
      intravenous/oral group, were managed as out-patients. Side effects were not
      observed. From this study, we can conclude that once-daily oral ceftibuten for 14
      days yielded comparable results to sequential ceftriaxone/ceftibuten treatment in
      children aged 6 months to 16 years with DMSA-documented acute pyelonephritis and
      it allowed out-patient management in the majority of these children.

PMID- 18074150
TI  - Paclitaxel (Taxol)-induced apoptosis in human epithelioid sarcoma cell lines is
      enhanced by upregulation of CD95 ligand (FasL/Apo-1L).
AB  - PURPOSE: Metastasizing epithelioid sarcoma (ES) is an extremely aggressive tumor,
      because conventional chemotherapy and irradiation are largely ineffective. Here,
      we analyzed the impact of the CD95-mediated drug-induced apoptosis in ES cell
      lines. METHODS: The effects of paclitaxel (Taxol) and 5-FU were determined by MTT
      assay. The extent of apoptosis was analyzed by light microscopy and Annexin V
      staining (flow cytometry). The expression of death receptors and ligands was
      defined by RT-PCR, Western blotting and flow cytometry. RESULTS: All cell lines
      expressed CD95, but not the CD95 ligand. The CD95 activation resulted in
      apoptosis and cell death in all cell lines. Both paclitaxel and 5-FU are able to
      trigger apoptosis, and furthermore, to upregulate CD95, whereas only paclitaxel
      increases CD95 ligand expression. Neutralizing antibodies directed against CD95
      ligand effectively inhibited paclitaxel-induced cell death, thereby providing
      evidence for a direct involvement of the CD95 system in paclitaxel-induced
      apoptosis. CONCLUSIONS: Concomitant upregulation of CD95 receptor and ligand may
      significantly enhance the response of ES to anticancer drugs. As evident from the
      differential response of our clonal ES subpopulations to paclitaxel and 5-FU,
      effective activation of the CD95 system depends on intrinsic properties of both
      the chemotherapeutic agent and target cell population.

PMID- 18074151
TI  - Dracunculiasis--the saddle is virtually ended.
AB  - Dracunculiasis is a preventable parasitic disease that for many years has
      affected poor communities without a safe portable water supply. Transmission is
      basically limited among the nomadic in remote rural settings. Most countries,
      including Asia, are declared free from the Guinea worm disease restraining the
      burden of transmission to Africa especially Sudan, Ghana, Mali, Nigeria and
      Niger. This review focuses mainly on the progress made so far by the Global
      Guinea Worm Eradication Programme championed by the Carter Center, Centers for
      Disease Control and Prevention, World Health Organisation, The United Nations
      Children's Fund and the individual efforts of endemic nations through their
      National Guinea Worm Eradication Programme aimed towards total global Guinea worm
      eradication.

PMID- 18074152
TI  - Ticks biting humans in the urban area of Istanbul.
AB  - A passive surveillance for tick bites in humans was undertaken in the city of
      Istanbul (Turkey) in the summer and autumn of 2006. From 1,054 reported tick
      bites, most were females of Ixodes ricinus (27%) and nymphs of Hyalomma aegyptium
      (50%). A few adults of Hyalomma m. marginatum, Rhipicephalus sanguineus and
      Dermacentor marginatus were also recorded. We investigated potential risk factors
      for I. ricinus and H. aegyptium with spatial statistics. Climate features at 1-km
      resolution (monthly minimum temperatures in late summer and autumn and rainfall)
      and vegetation features at high resolution (density and heterogeneity of forest
      type vegetation as well as distance of reporting site to these vegetation
      features) are useful variables explaining high reporting clusters for both Ixodes
      and Hyalomma. While Ixodes is highly reported in dense highly heterogeneous
      vegetation patches, Hyalomma is commonly found in areas far from forest-type
      features and in the small, relatively dry vegetation patches within the urban
      fabric.

PMID- 18074153
TI  - The life cycle of Stephanoprora aylacostoma n.sp. (Digenea: Echinostomatidae),
      parasite of the threatened snail Aylacostoma chloroticum (Prosobranchia,
      Thiaridae), in Argentina.
AB  - A new species, Stephanoprora aylacostoma is described and its life cycle was
      resolved experimentally. The prosobranch snail Aylacostoma chloroticum Hylton
      Scott, collected in the Yacyreta dam, Province of Misiones, Argentina, was found
      naturally infected with large-tailed cercariae possessing a prepharyngeal body
      and corpuscles in the excretory system but lacking collar spines. Metacercariae,
      which encysted on the gills of experimentally infected fishes Cnesterodon
      decemmaculatus (Jenyns) and Poecilia reticulata (Peters) (Poecilidae), developed
      collar spines after 10 days. Tetragonopterid fishes Moenckhausia dichroura
      (Kner), Astyanax erythropterus (Holmberg) and Hyphesobrycon serpae (Durbin in
      Eigenmann) were found infected naturally. Sexually mature adults were recovered
      from domestic chicks at day 7 post-exposure. Eggs shed in chick faeces developed
      to miracidia within 13-15 days; sporocysts were found on the gills of snails. The
      new species differs from other species of the genus in its larger eggs, in the
      smaller, slender body and smaller collar spines of the adult and in the
      morphological and biological features of the larval stages.

PMID- 18074154
TI  - Preparation of (R)-(-)-mandelic acid and its derivatives from racemates by
      enantioselective degradation with a newly isolated bacterial strain Alcaligenes
      sp. ECU0401.
AB  - An enantioselective mandelate-degrading bacterium, Alcaligenes sp. ECU0401, was
      newly isolated from soil. By fed-batch culture, (R)-(-)-mandelic acid was
      successfully prepared in a 5-L fermenter with 32.8% isolated yield and >99.9%
      enantiomeric excesses (e.e.) from totally 3.04% (w/v) of racemic mandelic acid
      after 99 h of biotransformation. The optimal reaction pH and temperature were 6.5
      and 30 degrees C, respectively. Using the resting cell as a biocatalyst for
      asymmetric degradation of racemic mandelic acid and chloro-substituted
      derivatives thereof, (R)-(-)-mandelic acid, (R)-(-)-o-chloromandelic acid, (S)
      (+)-m-chloromandelic acid and (S)-(+)-p-chloromandelic acid were recovered with
      high analytic yields and excellent enantiomeric excesses (e.e. > 99.9%). (R)-(-)
      Mandelic acid could also be obtained after 12 h of biotransformation with 41.5%
      isolated yield and >99.9% e.e.

PMID- 18074155
TI  - Kinetics of infective juvenile production of the entomopathogenic nematode
      Steinernema carpocapsae in submerged monoxenic culture.
AB  - The effects of culture medium formulations on the kinetics of infective juvenile
      (IJ) production of the entomopathogenic nematode Steinernema carpocapsae in
      submerged monoxenic culture, were studied at the cylindrical-bottle scale using
      six culture media containing agave juice from Agave spp. among other ingredients.
      The IJ production kinetics was well modelled through a re-parameterised 3
      parameter Gompertz model with kinetic parameters: IJ-lag phase lambda (IJ) (day),
      maximum IJ-stage production rate m (max )(day(-1)), and IJ-multiplication factor
      (C (IJ)/C (IJ,0))(max)(-). The variation of lambda (IJ) was not very important
      within fermentations (10.3-16.2 days); nonetheless, important effects were
      observed on m (max) (32.8-241.2 days(-1)) and (C (IJ)/C (IJ,0))(max) (66(-) to
      611.4(-)). Particularly, maximum values of m (max) and (C (IJ)/C (IJ,0))(max)
      were obtained in medium A4 (0.276 l l(-1) agave juice, 17 g l(-1) yeast extract,
      12 g l(-1) dried egg yolk, 0.025 l l(-1) corn oil). Also, the maximum IJ
      concentration (249,444 per ml) was achieved in A4-fermentations.

PMID- 18074156
TI  - Visual exploration of isotope labeling networks in 3D.
AB  - Isotope labeling networks (ILNs) are graphs explaining the flow of isotope
      labeled molecules in a metabolic network. Moreover, they are the structural
      backbone of metabolic flux analysis (MFA) by isotopic tracers which has been
      established as a standard experimental tool in fluxomics. To configure an isotope
      labeling experiment (ILE) for MFA, the structure of the corresponding ILN must be
      understood to a certain extent even by a practitioner. Graph algorithms help to
      analyze the network structure but produce rather abstract results. Here, the
      major obstruction is the high dimension of these networks and the large number of
      network components which, consequently, are hard to figure out manually. At the
      interface between theory and experiment, the three-dimensional interactive
      visualization tool CumoVis has been developed for exploring the network structure
      in a step by step manner. Navigation and orientation within ILNs are supported by
      exploiting the natural 3D structure of an underlying metabolite network with
      stacked labeled particles on top of each metabolite node. Network exploration is
      facilitated by rotating, zooming, forward and backward path tracing and, most
      important, network component reduction. All features of CumoVis are explained
      with an educational example and a realistic network describing carbon flow in the
      citric acid cycle.

PMID- 18074157
TI  - Thermal comfort in naturally ventilated and air-conditioned buildings in humid
      subtropical climate zone in China.
AB  - A thermal comfort field study has been carried out in five cities in the humid
      subtropical climate zone in China. The survey was performed in naturally
      ventilated and air-conditioned buildings during the summer season in 2006. There
      were 229 occupants from 111 buildings who participated in this study and 229
      questionnaire responses were collected. Thermal acceptability assessment reveals
      that the indoor environment in naturally ventilated buildings could not meet the
      80% acceptability criteria prescribed by ASHRAE Standard 55, and people tended to
      feel more comfortable in air-conditioned buildings with the air-conditioned
      occupants voting with higher acceptability (89%) than the naturally ventilated
      occupants (58%). The neutral temperatures in naturally ventilated and air
      conditioned buildings were 28.3 degrees C and 27.7 degrees C, respectively. The
      range of accepted temperature in naturally ventilated buildings (25.0-31.6
      degrees C) was wider than that in air-conditioned buildings (25.1-30.3 degrees
      C), which suggests that occupants in naturally ventilated buildings seemed to be
      more tolerant of higher temperatures. Preferred temperatures were 27.9 degrees C
      and 27.3 degrees C in naturally ventilated and air-conditioned buildings,
      respectively, both of which were 0.4 degrees C cooler than neutral temperatures.
      This result suggests that people of hot climates may use words like "slightly
      cool" to describe their preferred thermal state. The relationship between draught
      sensation and indoor air velocity at different temperature ranges indicates that
      indoor air velocity had a significant influence over the occupants' comfort
      sensation, and air velocities required by occupants increased with the increasing
      of operative temperatures. Thus, an effective way of natural ventilation which
      can create the preferred higher air movement is called for. Finally, the indoor
      set-point temperature of 26 degrees C or even higher in air-conditioned buildings
      was confirmed as making people comfortable, which supports the regulation in
      China that in public and office buildings the set-point temperature of air
      conditioning system should not be lower than 26 degrees C.

PMID- 18074158
TI  - Thionein/metallothionein control Zn(II) availability and the activity of enzymes.
AB  - Fundamental issues in zinc biology are how proteins control the concentrations of
      free Zn(II) ions and how tightly they interact with them. Since, basically, the
      Zn(II) stability constants of only two cytosolic zinc enzymes, carbonic anhydrase
      and superoxide dismutase, have been reported, the affinity for Zn(II) of another
      zinc enzyme, sorbitol dehydrogenase (SDH), was determined. Its log K is 11.2 +/-
      0.1, which is similar to the log K values of carbonic anhydrase and superoxide
      dismutase despite considerable differences in the coordination environments of
      Zn(II) in these enzymes. Protein tyrosine phosphatase 1B (PTP 1B), on the other
      hand, is not classified as a zinc enzyme but is strongly inhibited by Zn(II),
      with log K = 7.8 +/- 0.1. In order to test whether or not metallothionein (MT)
      can serve as a source for Zn(II) ions, it was used to control free Zn(II) ion
      concentrations. MT makes Zn(II) available for both PTP 1B and the apoform of SDH.
      However, whether or not Zn(II) ions are indeed available for interaction with
      these enzymes depends on the thionein (T) to MT ratio and the redox poise. At
      ratios [T/(MT + T) = 0.08-0.31] prevailing in tissues and cells, picomolar
      concentrations of free Zn(II) are available from MT for reconstituting apoenzymes
      with Zn(II). Under conditions of decreased ratios, nanomolar concentrations of
      free Zn(II) become available and affect enzymes that are not zinc metalloenzymes.
      The match between the Zn(II) buffering capacity of MT and the Zn(II) affinity of
      proteins suggests a function of MT in controlling cellular Zn(II) availability.

PMID- 18074159
TI  - A neonatal encephalopathy with seizures in standard poodle dogs with a missense
      mutation in the canine ortholog of ATF2.
AB  - Neonatal encephalopathy with seizures (NEWS) is a previously undescribed
      autosomal recessive disease of standard poodle puppies. Affected puppies are
      small and weak at birth. Many die in their first week of life. Those surviving
      past 1 week develop ataxia, a whole-body tremor, and, by 4 to 6 weeks of age,
      severe generalized clonic-tonic seizures. None have survived to 7 weeks of age.
      Cerebella from affected puppies were reduced in size and often contained
      dysplastic foci consisting of clusters of intermixed granule and Purkinje
      neurons. We used deoxyribonucleic acid samples from related standard poodles to
      map the NEWS locus to a 2.87-Mb segment of CFA36, which contains the canine
      ortholog of ATF2. This gene encodes activating transcription factor 2 (ATF-2),
      which participates in the cellular responses to a wide variety of stimuli. We
      amplified and sequenced all coding regions of canine ATF2 from a NEWS-affected
      puppy and identified a T > G transversion that predicts a methionine-to-arginine
      missense mutation at amino acid position 51. Methionine-51 lies within a
      hydrophobic docking site for mitogen-activated protein kinases that activate ATF
      2 so the arginine substitution is likely to interfere with ATF-2 activation. All
      20 NEWS-affected puppies in the standard poodle family were homozygous for the
      mutant G allele. The 58 clinically normal family members were either G/T
      heterozygotes or homozygous for the ancestral T allele. There are no previous
      reports of spontaneous ATF2 mutations in people or animals; however, atf2
      knockout mice have cerebellar lesions that are similar to those in puppies with
      NEWS.

PMID- 18074160
TI  - SCCmec and spa types of methicillin-resistant Staphylococcus aureus strains in
      Israel. Detection of SCCmec type V.
AB  - Molecular characterization of methicillin-resistant Staphylococcus aureus
      isolates from three hospitals in Israel was the aim of the study presented here.
      We identified 11 distinct genetic clones by pulsed-field gel electrophoresis.
      Molecular typing identified four different SCCmec types-I, II, IV, and V-and nine
      spa types. Spa type t002 was the most common.

PMID- 18074161
TI  - The effects of gender and age on REM-related sleep-disordered breathing.
AB  - Sleep disordered breathing occurring predominantly in rapid eye movement REM
      sleep (rapid-eye-movement-related sleep-disordered breathing, REM SDB) is present
      in 10 to 36% of patients undergoing polysomnography (PSG) for suspected
      obstructive sleep apnea (O'Connor et al. in Am J Respir Crit Care Med 161:1465
      1472, 2000; Resta et al. in J Respir Medicine 99:91-96, 2005; Haba-Rubio et al.
      in Chest 128:3350-3357, 2005; Juvelekian and Golish, American Academy of Sleep
      Medicine, abstract, 2004). We hypothesize that REM SDB is an age-related
      condition in women and, additionally, more prevalent in women than in men.
      Subjects with REM SDB were identified retrospectively among 1,540 obstructive
      sleep apnea (OSA) patients with an apnea-hypopnea index (AHI) >or= 5. Inclusion
      criteria for REM SDB were age >18, AHI >or= 5, NREM AHI < 15, and REM AHI/NREM
      AHI > 2. PSG data included sleep latency, REM latency, total sleep time (TST),
      AHI, REM AHI, NREM AHI, and sleep stage percentages. Demographic data and medical
      and psychiatric histories were also obtained. Statistical comparisons were made
      between men and women and women older and younger than 55 years, a marker for
      menopausal status. Two hundred twenty-one subjects fulfilled the criteria for REM
      SDB, yielding a prevalence of 14.4%. Overall, female apneics had a significantly
      higher prevalence of REM SDB than did men (24.5 vs 7.9%; p < 0.001). Younger
      women had a significantly higher prevalence than did older women (27.2 vs 18.6%;
      p = 0.008); younger men had a significantly higher prevalence of REM SDB than did
      older men (9.9 vs 4.5%; p = 0.002). Women were significantly older and more obese
      than were men. Younger women were more likely to be depressed and were
      significantly more obese than were older women. REM SDB is more prevalent in
      women than in men and more prevalent in men and women younger than 55 than those
      older than 55. In this population, women are more obese and older than men, while
      younger women were more obese than older women. These descriptive distinctions
      suggest differences in mechanism which may depend on gender and age.

PMID- 18074162
TI  - Exhaled breath markers in patients with obstructive sleep apnoea.
AB  - The objectives of the present study were to assess the level of exhaled breath
      markers indicating airway inflammation and oxidative stress in patients with
      obstructive sleep apnoea syndrome (OSAS) in comparison with non-apnoeic (obese
      and non-obese) subjects and investigate whether therapy with continuous positive
      airway pressure (CPAP) can modify them. The design was a retrospective
      observational study, set in Evgeneidio Hospital. Twenty-six OSAS patients and
      nine obese and 10 non-obese non-apnoeic subjects participated in this study. We
      measured nasal nitric oxide (nNO), exhaled nitric oxide (eNO), exhaled carbon
      monoxide (eCO) in exhaled breath, and 8-isoprostane, leukotriene B(4) (LTB(4)),
      nitrates, hydrogen peroxide (H(2)O(2)), and pH in exhaled breath condensate (EBC)
      before and after 1 month of CPAP therapy. The levels of eNO and eCO were higher
      in OSAS patients than in control subjects (p < 0.05). Nasal NO was higher in OSAS
      patients than in obese controls (p < 0.01). The level of H(2)O(2), 8-isoprostane,
      LTB(4), and nitrates were elevated in OSAS patients in comparison with obese
      subjects (p < 0.01). Conversely, pH was lower in OSAS patients than in non
      apnoeic controls (p < 0.01). One month of CPAP therapy increased pH (p < 0.05)
      and reduced eNO (p < 0.001) and nNO (p < 0.05). Apnea/hypopnoea index was
      positively correlated with 8-isoprostane (r = 0.42; p < 0.05), LTB(4) (r = 0.35;
      p < 0.05), nitrates (r = 0.54; p < 0.001), and H(2)O(2) (r = 0.42; p < 0.05).
      Airway inflammation and oxidative stress are present in the airway of OSAS
      patients in contrast to non-apnoeic subjects. Exhaled breath markers are
      positively correlated with the severity of OSAS. One-month administration of CPAP
      improved airway inflammation and oxidative stress.

PMID- 18074163
TI  - [Nobel Price for Medicine 2007. Knockout mice are revolutionizing genetics].

PMID- 18074164
TI  - Shear bond strength of composite bonded to erbium:yttrium-aluminum-garnet laser
      prepared dentin.
AB  - The purpose of this study was to evaluate the dentin bond strength to resin
      composite following erbium:yttrium-aluminum-garnet (Er:YAG) laser preparation
      using different adhesive systems. Seventy dentin specimens prepared from human
      molar teeth were randomly assigned to seven groups of ten. The first five groups
      were prepared with an Er:YAG laser 2940 nm at the manufacturer's recommended
      settings and (1) acid etched, and etch-and-rinse adhesive Excite was applied; (2)
      Excite was applied; (3) two-step self-etching adhesive AdheSE was applied; (4)
      laser etched (120 mJ/10 Hz), and Excite was applied; (5) laser etched, and AdheSE
      was applied. The last two groups were added as controls (prepared with a diamond
      bur): (6) acid etched, and Excite was applied; (7) AdheSE was applied. Nanohybrid
      composite cylinders 4 mm x 2 mm were bonded to the dentin surfaces. After the
      specimens had been stored in distilled water and had undergone thermocycling, the
      shear bond strength was tested and the data were analyzed statistically. The
      Duncan multiple comparison test showed that specimens prepared with a diamond bur
      and with acid and Excite applied showed the highest mean bond strength (13.01 +/-
      2.09 MPa), followed by those prepared with Er:YAG and with AdheSE applied (11.5
      +/- 3.59 MPa) and those prepared with a diamond bur and with AdheSE applied
      (10.75 +/- 1.95 MPa), but there were no significant differences among them (P >
      0.05). Er:YAG-prepared specimens, with acid, Excite (3.28 +/- 0.95 MPa) and
      specimens that were laser etched and with AdheSE applied (3.37 +/- 0.63 MPa)
      showed the lowest mean values for bond strength (P < 0.05). The results suggested
      that dentin surfaces prepared with Er:YAG laser may provide comparable composite
      resin bond strengths depending on the adhesives used.

PMID- 18074165
TI  - Outcome of erbium:yttrium aluminium garnet laser resurfacing treatments.
AB  - Erbium:yttrium aluminium garnet (erbium:YAG) laser treatment was used to
      resurface skin abnormalities in patients suffering from conditions that included
      epidermal naevi, tuberous sclerosis, angiofibromata, neurofibromatosis, and
      scarring caused by acne or other means. Patients completed self-report
      questionnaires before their first laser test patch session, and again
      approximately 4 months after one treatment, so that its success could be
      evaluated from the patient's perspective. Disability and distress were quantified
      with the University of York Health Measurement Questionnaire (HMQ). Satisfaction
      with appearance was measured with a specifically designed Salisbury Appearance
      Scale (SAS) questionnaire. Pretreatment questionnaires were completed by 108
      (HMQ) and 80 (SAS) patients. Thirty-six (HMQ) and 22 (SAS) patients completed a
      full treatment during the study period. Some patients had a test patch only
      during the study period. Others decided against further treatment after the test
      patch. Control SAS questionnaires were completed by 29 subjects on two occasions
      and showed no change over time. There was a significant improvement in patient
      satisfaction with appearance (SAS), but there was no significant difference in
      the disability and distress (HMQ) after erbium:YAG resurfacing.

PMID- 18074166
TI  - Theoretical modelling in bioengineering: 12th Haughton Lecture of the Royal
      Academy of Medicine in Ireland.
AB  - This paper is concerned with the role of theoretical modelling in bioengineering
      research. The subject matter was delivered as the 12th annual Haughton Lecture,
      presented on 28 January 2006 at the Bioengineering in Ireland conference in
      Galway. The title of the lecture was "Telling Stories About Bone". The paper
      begins with some general remarks about what constitutes a scientific theory, and
      it moves on to a discussion about where ideas for theoretical models come from,
      taking examples from my own work on the mechanical strength and fracture of bone.
      I conclude with some advice to budding theoreticians.

PMID- 18074167
TI  - Regulation and function of lysine-substituted Na,K pumps in salt adaptation of
      Artemia franciscana.
AB  - The brine shrimp Artemia thrives at extreme conditions of up to 300 g/l salt in
      hypersaline lakes, but the molecular aspects of this salt adaptation are not
      clarified. To examine the influence of salt on the expression of two isoforms of
      Na,K-ATPase, adult Artemia franciscana were cultured for 39 days with the
      microalga Dunaliella salina as fodder at increasing salt from 30 to 280 g/l.
      Quantitative reverse-transcriptase polymerase chain reaction showed that the
      abundance of mRNA of the lysine-substituted alpha(2)(KK)-subunit was very low at
      30 g/l salt but rose steeply in the range of 70-200 g/l to a level at 200-280 g/l
      salt, similar to the abundance of the mRNA of the alpha(1)(NN)-subunit, which was
      insignificantly affected by increasing salt. Site-directed mutagenesis showed
      that Asn324Lys and Asn776Lys in the alpha(1)-subunit of pig kidney Na,K-ATPase
      reduced the stoichiometry of (204)Tl binding from 2 to about 1 Tl(+)(K(+)) per
      alpha-subunit and Na(+)-dependent phosphorylation from ATP to 25-30%. In
      structure models, the epsilon-amino group of Lys776 is located at cation site 1
      in the E(1)P form and near cation site 2 in the E(2) conformation, while the side
      chain of Lys324 points away from the cation sites. Salt-induced expression of the
      alpha(2)(KK)-subunit Na,K-ATPase in A. franciscana may reduce the Na(+)/ATP ratio
      and enable the Na,K pump to extrude Na(+) against steeper gradients and, thus,
      contribute to salt adaptation.

PMID- 18074168
TI  - Double-outlet left ventricle with a superiorly positioned and hypoplastic left
      ventricle.
AB  - Double outlet left ventricle (DOLV) is a rare congenital cardiac malformation in
      which both the pulmonary artery and the aorta arise exclusively or predominantly
      from the morphologic left ventricle. We describe a case of DOLV with situs
      inversus, L-loop ventricles, d-malposition of the great arteries (I, L, D),
      superior-inferior ventricles, unbalanced complete atrioventricular septal defect,
      pulmonary stenosis, and total anomalous pulmonary venous return in which the left
      ventricle was also severely hypoplastic and superiorly positioned. Many
      morphologic variations of this malformation have been described, but to the best
      of our knowledge DOLV with superiorly positioned and hypoplastic left ventricle
      has not been reported before.

PMID- 18074169
TI  - Comparative mesocosm study of biostimulation efficiency in two different oil
      amended sub-antarctic soils.
AB  - Biological treatment has become increasingly popular as a remediation method for
      soils and groundwater contaminated with petroleum hydrocarbon, chlorinated
      solvents, and pesticides. Bioremediation has been considered for application in
      cold regions such as Arctic and sub-Arctic climates and Antarctica. Studies to
      date suggest that indigenous microbes suitable for bioremediation exist in soils
      in these regions. This paper reports on two case studies at the sub-Antarctic
      Kerguelen Island in which indigenous bacteria were found that were capable of
      mineralizing petroleum hydrocarbons in soil contaminated with crude oil and
      diesel fuel. All results demonstrate a serious influence of the soil properties
      on the biostimulation efficiency. Both temperature elevation and fertilizer
      addition have a more significant impact on the microbial assemblages in the
      mineral soil than in the organic one. Analysis of the hydrocarbons remaining at
      the end of the experiments confirmed the bacterial observations. Optimum
      temperature seems to be around 10 degrees C in organic soil, whereas it was
      higher in mineral soil. The benefit of adding nutrients was much stronger in
      mineral than in the organic soil. Overall, this study suggests that
      biostimulation treatments were driven by soil properties and that ex situ
      bioremediation for treatment of cold contaminated soils will allow greater
      control over soil temperature, a limiting factor in cold climates.

PMID- 18074170
TI  - Perceiving the environment from the lay perspective in desertified areas,
      northern China.
AB  - Investigating local people's environmental perceptions can produce useful
      information that could be incorporated into decision making processes that help
      resolve environmental problems. Although China is undergoing severe
      desertification, the perceptions of the local people toward their degraded
      environment and the related issues have so far not been actively solicited. This
      article, which is a supplement to Lee and Zhang's (2004, 2005) studies, seeks to
      further investigate the lay public's general environmental attitudes, perceptions
      of desertification, interpretations of land-degrading activities, and
      particularly their interrelations in severely desertified areas. Minqin County in
      Gansu Province, northern China, was chosen to be the study area. Data was
      collected via a questionnaire survey (n=1138) administered in December 2002.
      Major findings were: (1) Most respondents had only weak altruistic environmental
      attitudes, with educational level to be a significant determinant. (2)
      Respondents' perceptions of desertification and interpretations of land-degrading
      activities were contingent on personal attributes, general environmental
      attitudes, and other conceptions related to desertification. It is recommended
      that the interrelations between the various aspects of the public's environmental
      perceptions should be thoroughly examined to facilitate their participation in
      environmental management.

PMID- 18074171
TI  - The potential role for xanthine oxidase inhibition in major intra-abdominal
      surgery.
AB  - BACKGROUND: Xanthine oxidase (XO) is a cytosolic metalloflavoprotein that has
      been implicated in the pathogenesis of a wide spectrum of diseases, and is
      thought to be the most important source of oxygen-free radicals and cell damage
      during re-oxygenation of hypoxic tissues. Clinical studies have already shown
      that XO inhibition is safe and effective for the treatment of gout, tumour-lysis
      syndrome, and to reduce complications such as post-operative arrhythmias,
      myocardial infarction and mortality in cardiovascular surgery. Here, we review
      the evidence from two decades of animal studies that have investigated the
      effects of XO inhibition during intra-abdominal surgery. MATERIALS AND METHODS: A
      search of the Ovid MEDLINE database from 1950 through January 2007 was carried
      out using the following search terms: xanthine oxidase, allopurinol, ischemia,
      reperfusion, intestine, bowel, and general surgery. RESULTS: The inhibition of XO
      has been shown to reduce oxidative stress, neutrophil priming, damage to
      intestinal mucosa due to ischemia reperfusion injuries, intestinal anastomotic
      dehiscence, bacterial translocation, adhesion formation, distant organ injury and
      mortality. CONCLUSIONS: Despite this evidence which very strongly suggests a
      likely clinically beneficial role for XO inhibition in the elective and acute
      operative setting, it is surprising that such an approach has not been
      investigated in general surgery. There is now sufficient evidence to justify
      dedicated studies to determine the clinical benefits, dosing and duration of XO
      inhibition before and after gastrointestinal surgery.

PMID- 18074172
TI  - The clinical conundrum of corticotropin-independent autonomous cortisol secretion
      in patients with bilateral adrenal masses.
AB  - BACKGROUND: Management of patients with bilateral adrenal masses and
      corticotropin (ACTH)-independent Cushing syndrome (CS) or subclinical CS is
      problematic. We report our experience with adrenal venous sampling (AVS) in the
      evaluation of 10 patients with bilateral masses who had ACTH-independent CS or
      subclinical CS. PATIENTS AND METHODS: Ten patients (9 women, 1 man, mean age 56.4
      years) with bilateral adrenal masses and ACTH-independent CS (n=3) or subclinical
      CS (n=7) underwent AVS. Autonomous cortisol secretion was documented in all cases
      with suppressed serum ACTH concentrations and lack of cortisol suppression with
      dexamethasone administration. Adrenal venous sampling was performed on the second
      day of dexamethasone administration. Cortisol and epinephrine levels were
      measured from each adrenal vein (AV) and from a peripheral vein (PV). RESULTS:
      Mean (+/-SD) maximal diameter of the adrenal masses on computed tomography was
      3.3+/-1.3 cm (range: 1.2-6.0 cm). Successful catheterization was confirmed with
      AV:PV epinephrine gradients. A cortisol AV:PV gradient>6.5 was consistent with a
      cortisol-secreting adenoma in 11 adrenal glands; 5 patients had clinically
      important bilateral autonomous cortisol hypersecretion, 3 had bilateral cortisol
      secreting adenomas, and 2 had ACTH-independent macronodular adrenal hyperplasia.
      Adrenal venous sampling-guided adrenalectomy was completed in all 10 patients-2
      patients had total bilateral adrenalectomy and 2 others had subtotal bilateral
      adrenalectomy. During a mean follow-up of 36.1 months (range: 0.7-123 months), CS
      or clinically important cortisol secretory autonomy did not recur. CONCLUSIONS:
      Adrenal venous sampling contributed to the localization of autonomous
      hypercortisolism in the setting of ACTH-independent CS or subclinical CS in
      patients with bilateral adrenal masses.

PMID- 18074173
TI  - Outpatient management of postbiopsy pneumothorax with small-caliber chest tubes:
      factors affecting the need for prolonged drainage and additional interventions.
AB  - The aim of this study was to evaluate the efficacy of outpatient management of
      postbiopsy pneumothoraces with small-caliber chest tubes and to assess the
      factors that influence the need for prolonged drainage or additional
      interventions. We evaluated the medical records of patients who were treated with
      small-caliber chest tubes attached to Heimlich valves for pneumothoraces
      resulting from image-guided transthoracic needle biopsy to determine the hospital
      admission rates, the number of days the catheters were left in place, and the
      need for further interventions. We also evaluated the patient, lesion, and biopsy
      technique characteristics to determine their influence on the need for prolonged
      catheter drainage or additional interventions. Of the 191 patients included in
      our study, 178 (93.2%) were treated as outpatients. Ten patients (5.2%) were
      admitted for chest tube-related problems, either for underwater suction (n = 8)
      or for pain control (n = 2). No further interventions were required in 146
      patients (76.4%), with successful removal of the chest tubes the day after the
      biopsy procedure. Prolonged catheter drainage (mean, 4.3 days) was required in 44
      patients (23%). Nineteen patients (9.9%) underwent additional interventions for
      management of pneumothorax. Presence of emphysema was noted more frequently in
      patients who required additional interventions or prolonged chest tube drainage
      than in those who did not (51.1% vs. 24.7%; p = 0.001). We conclude that use of
      the Heimlich valve allows safe and successful outpatient treatment of most
      patients requiring chest tube placement for postbiopsy pneumothorax. Additional
      interventions or prolonged chest tube drainage are needed more frequently in
      patients with emphysema in the needle path.

PMID- 18074174
TI  - Biochemical markers of bone turnover in percutaneous vertebroplasty for
      osteoporotic compression fracture.
AB  - PURPOSE: To evaluate relationships between biochemical markers of bone turnover,
      bone mineral density, and new compression fractures following vertebroplasty.
      METHODS: Initially, we enrolled 30 consecutive patients with vertebral
      compression fractures caused by osteoporosis. Twenty-three of the 30 patients
      visited our hospital for follow-up examinations for more than 4 weeks after
      vertebroplasty. The patients were divided into two groups: patients with new
      fractures (group F) and patients with no new fractures (group N). We analyzed
      differences in the following parameters between these two groups: serum bone
      alkaline phosphatase, urinary crosslinked N-telopeptide of type I collagen,
      urinary deoxypyridinoline, and bone mineral density. Next, the patients were
      divided into another two groups: patients with higher risk (group H: urinary
      crosslinked N-telopeptide of type I collagen >54.3 nmol BCE/mmol Cr or urinary
      deoxypyridinoline >7.6 nmol/mmol Cr, and serum bone alkaline phosphatase <29.0
      U/l) and patients with lower risk (group L). We analyzed the difference in the
      rate of new fractures between these two groups. RESULTS: We identified 9 new
      fractures in 7 patients. There were no significant differences between groups F
      and N. We identified 5 new fractures in 3 of the 4 patients in group H, and 4 new
      fractures in 4 of the 19 patients in group L. There was a significant difference
      in the rate of new fractures between groups H and L. CONCLUSIONS: A combination
      of high levels of bone resorption markers and normal levels of bone formation
      markers may be associated with increased risk of new recurrent fractures after
      percutaneous vertebroplasty.

PMID- 18074175
TI  - Characterization of a homogentisate dioxygenase mutant in Pseudomonas
      chlororaphis O6.
AB  - Transposon mutagenesis of Pseudomonas chlororaphis O6 was performed with the
      transposon Tn5 to investigate genes involved in production of secondary
      metabolites. A mutant, termed Org, produced intense dark-brown pigmentation on
      rich medium. The Tn5-flanking sequence of the Org mutant showed high homology
      with the hmgA gene encoding the enzyme homogentisate dioxygenase, involved in the
      degradation of aromatic amino acids such as tyrosine. Growth of the hmgA mutant
      on L-tyrosine as sole carbon and energy sources was impaired. Growth on L
      tyrosine was restored and production of the brown melanin pigment was eliminated
      when the mutant was complemented with the wild-type hmgA gene. The change in
      aromatic amino acids metabolism caused by the deletion of the hmgA gene function
      did not impair production of phenazines and biological traits connected to these
      secondary compounds: inhibition of fungal growth and inhibition of barley seed
      germination.

PMID- 18074176
TI  - Characterization of two 2[4Fe4S] ferredoxins from Clostridium acetobutylicum.
AB  - In vivo hydrogen production in Clostridium acetobutylicum involves electron
      transfer between ferredoxin and [FeFe]-hydrogenase. Five C. acetobutylicum open
      reading frames were annotated as coding for putative ferredoxins. We focused our
      biophysical and biochemical investigations on CAC0303 and CAC3527, which possess
      the sequence signature and length of classical 2[4Fe4S] clostridial ferredoxins
      but differ significantly in theoretical pI. After cloning, heterologous
      expression in E. coli followed by in vitro Fe-S incorporation and purification,
      CAC0303 was shown to have a regular electron paramagnetic resonance (EPR) signal
      for a classical 2[4Fe4S] clostridial ferredoxin, while CAC3527 displayed an
      unusual EPR signal and a quite low reduction potential. Both ferredoxins were
      reduced in vitro by C. acetobutylicum [FeFe]-hydrogenase, but the CAC3527
      reduction rate was 10-fold lower than that of CAC0303. These results are
      consistent with the efficiency of intermolecular electron transfer being dictated
      by the redox thermodynamics, the contribution of the ferredoxin global charge
      being only minor. The physiological function of CAC3527 is discussed.

PMID- 18074177
TI  - Antagonistic activity of potential probiotic Lactobacilli against the ureolytic
      pathogen Yersinia enterocolitica.
AB  - Strains of Lactobacillus spp., isolated from sourdough and olive brines (seven
      strains), and three human isolates were screened for their antagonistic activity
      in coculture against the ureolytic pathogen Yersinia enterocolitica. A general
      reduction in the pathogen population was observed after 6 h when each
      Lactobacillus strain was cocultured with the pathogen at a ratio of 100:1 cfu ml(
      1), causing an almost complete inhibition of urease activity. Strains were also
      screened for their performances in in vitro tests such as adhesion ability to
      Caco-2 cells, tolerance to low pH, bile salts, and simulated digestion, which
      enabled the differences between strains to be highlighted. Three strains, L.
      paracasei IMPC2.1 and L. plantarum ITM21B and ITM5BG, met the main criteria for
      selecting effective probiotics: the ability to inhibit the pathogen Y.
      enterocolitica and, consequently, its urease activity (ITM21B); survival of
      simulated digestion (ITM21B and IMPC2.1); strong adhesion ability to enterocytes
      and good survival at low pH and in the presence of bile salts (ITM5BG and
      IMPC2.1).

PMID- 18074178
TI  - Isolation and characterization of nonrhizobial plant growth promoting bacteria
      from nodules of Kudzu (Pueraria thunbergiana) and their effect on wheat seedling
      growth.
AB  - The leguminous vine Kudzu (Pueraria thunbergiana) is an introduction into the N.
      W. Himalayan region of India. Despite its value as a fodder and cover crop,
      little is known about the nature of the nodule microflora. In an attempt to study
      the nodule bacteria, we isolated and characterized three nonrhizobial plant
      growth promoting bacteria from surface sterilized nodules of Kudzu. Based on the
      sequencing of the 16 S r RNA gene, the isolates were designated as Bacillus
      thuringiensis KR-1, Enterobacter asburiae KR-3, and Serratia marcescens KR-4.
      Crystalline bodies were detected in the isolate KR-1, confirming its identity as
      B. thuringiensis. Under in vitro conditions, all three isolates were found to
      produce indole acetic acid. Other plant growth promotion attributes such as P
      solubilization, hydrogen cyanide production, and ammonia production varied among
      the isolates. All of the three isolates promoted growth and positively influenced
      nutrient uptake parameters of wheat seedlings.

PMID- 18074179
TI  - Carbon dioxide directly suppresses spontaneous migration, chemotaxis, and free
      radical production of human neutrophils.
AB  - BACKGROUND: Carbon dioxide (CO(2)) insufflation during laparoscopy has been shown
      to dampen the systemic stress response to surgery. This is related to a
      suppression of peritoneal macrophage functions. In vivo data suggest that CO(2)
      can also affect neutrophils (polymorphonuclear cells, PMNs), the most abundant
      cell type in the inflamed peritoneal cavity. Nonetheless, the direct effects of
      CO(2) on PMNs have not yet been investigated. METHOD: PMNs were isolated from
      peripheral blood of healthy volunteers and incubated with (1) CO(2) (100% CO(2),
      pH 6.2), (2) hypoxic control (95% helium/5% CO(2), pH 7.4), and (3) control (95%
      air/5% CO(2), pH 7.4). Spontaneous and IL-8-induced migrations (chemokinesis and
      chemotaxis) during 2 h of exposure to different gases were measured with a
      transwell chamber system. The release of reactive oxygen species (ROS,
      luminometry) was determined after 15-min and 2-h exposures. In other sets of
      experiments, PMNs were exposed for 2 h or 4 h and kept under normal conditions
      for 18 h with lipopolysaccharide (LPS) stimulation thereafter. Final viability
      and apoptosis were assessed with fluorometry. RESULTS: Exposure to 100% CO(2)
      completely blocked spontaneous and IL-8 induced migration of PMNs (p < 0.001 vs.
      controls). Neutrophil migration was slightly diminished in the hypoxic control
      group. PMA-stimulated ROS production was reduced even after short exposure to
      100% CO(2)(p < 0.05). We observed a slight increase of caspase-3/7 activity after
      exposure to 100% CO(2) and/or hypoxia; however, total viability was not affected.
      CONCLUSIONS: CO(2) incubation directly and temporarily suppresses the
      proinflammatory functions of PMNs; this is caused only partially by the
      concomitant hypoxia. This effect will contribute to the dampened inflammatory
      response to laparoscopic surgery. Further studies are needed to investigate
      whether the temporary suppression of neutrophil functions could affect the
      clearance of bacterial contaminations.

PMID- 18074180
TI  - Laparoscopic and endoscopic cooperative surgery for gastrointestinal stromal
      tumor dissection.
AB  - BACKGROUND: Laparoscopic wedge resections are increasingly applied for gastric
      submucosal tumors such as gastrointestinal stromal tumor (GIST). Despite this, no
      defined strategy exists to guide the surgeon in choosing the appropriate
      laparoscopic technique for an individual case on the basis of tumor
      characteristics such as location or size. This study aimed to introduce a
      laparoscopic and endoscopic cooperative surgery (LECS) for gastric wedge
      resection that is applicable for submucosal tumor resection independent of tumor
      location and size. METHODS: Seven patients underwent LECS for the resection of
      gastric submucosal tumors. Both mucosal and submucosal layers around the tumor
      were circumferentially dissected using endoscopic submucosal dissection via
      intraluminal endoscopy. Subsequently, the seromusclar layer was laparoscopically
      dissected on the exact three-fourths cut line around the tumor. The submucosal
      tumor then was exteriorized to the abdominal cavity and dissected with a standard
      endoscopic stapling device. RESULTS: In all cases, the LECS procedure was
      successful for dissecting out the gastric submucosal tumor. In four of seven
      cases, the tumor was located in the upper gastric portion near the
      esophagogastric junction. The remaining three tumors were in the posterior
      gastric wall. In two cases, the tumors were more than 5 cm in diameter, and one
      was a GIST of the remnant stomach. The mean operation time was 169 +/- 17 min,
      and the estimated blood loss was 7 +/- 2 ml. The postoperative course was
      uneventful in all cases. CONCLUSIONS: The LECS procedure for dissection of
      gastric submucosal tumors such as GIST may be performed safely with reasonable
      operation times, less bleeding, and adequate cut lines. In addition, the success
      of the procedure does not depend on the tumor location such as the vicinity of
      the esophagogastric junction or pyloric ring.

PMID- 18074181
TI  - Establishing a simulation center for surgical skills.

PMID- 18074182
TI  - Transumbilical laparoscopically assisted appendectomy in children: high-tech low
      budget surgery.
AB  - BACKGROUND: Two different laparoscopic appendectomy (LA) techniques, one
      performed with staplers (LAS) and the other using loops (LAL), were compared with
      transumbilical laparoscopically assisted appendectomy (TULAA). METHODS: A total
      of 72 children, 55 with a diagnosis of uncomplicated acute appendicitis and 17
      with recurrent right lower abdominal pain, underwent operation during the period
      2003-2006. The procedures used were: 34 LAS, 9 LAL, and 29 TULAA. Measured
      outcomes were operative time, postoperative complications, need for rescue
      analgesics, length of hospital stay, and procedure cost reflected by supplies
      used. The staplers, endoloops, clips, and sutures used to manage appendectomy
      were listed at current prices, summarized as number consumed per case, and
      compared. Data were analyzed by Fisher's exact test and the Mann-Whitney U-test
      where appropriate. Statistical significance was determined as p < 0.05. RESULTS:
      Average price of materials used was 113.5 USD for LAS, 91 USD for LAL, and 14 USD
      for TULAA. Wound infections were recorded in two patients (4.6%) in the LA group
      and in four patients (13.7%) in the TULAA group (p = 0.17). One patient in the
      LAL group developed an abdominal abscess that was managed conservatively. Median
      operating time was 39 (24-66) min in the LA group versus 33 (25-55) min in the
      TULAA group (p < 0.05). Rescue analgesia was administered in 19/43 (44%) of LA
      patients and 9/29 (31%) of TULAA patients (p = 0.19). The length of hospital stay
      was 3.1 days for LA patients and 3.0 days for TULAA patients (p = 0.43). Two
      TULAA procedures (6.4%) were finished with additional port/s. CONCLUSIONS: In
      this study, the cost of TULAA is 7.8 times lower than the cost of LA, 8.1 times
      lower than LAS, and 6.5 times lower than LAL. Higher cost of laparoscopy is
      solely attributable to the purchase price of the supplies used. Overall
      postoperative morbidity, the incidence of wound infection, the length of
      hospitalization, and the need for rescue analgesia did not show a statistical
      difference in comparing LA/TULAA. Operative time was shorter in the TULAA group.
      In terms of limited resources, TULAA could be the most appropriate minimally
      invasive technique for appendectomy in children.

PMID- 18074183
TI  - Long-term quality of life after endoscopic dilation of strictured colorectal or
      colocolonic anastomoses.
AB  - BACKGROUND: Endoscopic balloon dilation is the first-line treatment for benign
      colorectal anastomotic strictures. We aimed to objectively assess its long-term
      results. METHODS: Gastrointestinal symptoms and health-related quality of life
      (HRQoL) were assessed at long-term after balloon dilation of anastomotic
      strictures in 31 consecutive patients (excluding those with inflammatory bowel
      disease) as well as and controls, using the validated Gastrointestinal Quality of
      Life Index (GIQLI). Most colectomies had been performed for benign diseases, with
      anastomoses located at the colorectal junction. RESULTS: Completed surveys were
      collected from 81 subjects, including 27 study patients (response rate 87%), 27
      surgical controls matched for age, gender, and indication of colectomy, and 27
      healthy subjects. At a mean of 3.9 +/- 2.3 years after the first endoscopic
      balloon-dilation, study patients self-reported significantly more
      gastrointestinal symptoms than controls; these included frequent and urgent bowel
      movements, bloating, food restriction (p < or = 0.001, all comparisons),
      diarrhea, excessive passage of gas through the anus (p < 0.01, all comparisons),
      constipation, and abdominal pain (p < 0.05, all comparisons). Health-related
      quality of life was significantly impaired in study patients versus surgical
      controls and healthy subjects (GIQLI scores, 104 +/- 20, 119 +/- 24, and 121 +/-
      16, respectively; p = 0.005). Impaired HRQoL subdimensions included
      gastrointestinal symptoms (p < 0.001), stress by treatment (p < 0.05), and
      emotional status (p = 0.08). HRQoL was independent of the delay between stricture
      dilation and the survey. Follow-up endoscopy (performed in 21/27 [78%] study
      patients, including the 7 patients with the lowest HRQoL, and 19 [70%] surgical
      controls) disclosed anastomoses larger than 13 mm in all cases. CONCLUSIONS:
      Health-related quality of life is significantly impaired at long-term after
      standard balloon-dilation of benign anastomotic colorectal strictures as a result
      of gastrointestinal symptoms and stress by treatment. This impairment might be
      related to the fact that an anastomotic diameter > or = 13 mm, although commonly
      used to define successful endoscopic treatment, is insufficient to provide long
      term symptom relief in some patients, or to other, yet to be identified, factors.

PMID- 18074184
TI  - Improving rates for screening colonoscopy: Analysis of the health information
      national trends survey (HINTS I) data.
AB  - BACKGROUND: Colonoscopy is an effective modality for colorectal cancer screening.
      The objectives of this study were to identify colorectal cancer knowledge and
      barriers to screening colonoscopy in the general US population. METHODS: Data was
      obtained from the health information national trends survey (HINTS I). The
      dataset (n = 6369) examined the influence of age, race, gender, education,
      income, media usage, and interactions with health care providers on knowledge,
      attitudes, and behavior regarding colonoscopic screening for colorectal cancer.
      RESULTS: The term 'colonoscopy' was recognized by 80% of participants (over the
      age of 35), however only 35% of respondents perceived it as a major method for
      colon cancer screening. Hispanics had the least awareness of colonoscopic
      screening (16% versus 39% non-Hispanic). Female gender, education, and income all
      correlated with knowledge and use of colonoscopic screening. There was a positive
      correlation between media usage and having a colonoscopy (r = 0.095, p < 0.01).
      Having a health care provider was strongly correlated with having undergone a
      colonoscopy (r = 0.249, p < 0.01). Reasons for not having a colonoscopy were 'no
      reason' (29%), 'doctor didn't order it' (24%), and 'didn't know I needed the
      test' (15%). Personalized materials were the preferred media for receiving cancer
      related information. CONCLUSIONS: Knowledge of and participation in screening
      colonoscopy is low in the US population, especially among Hispanics. The most
      important immediate action is to increase physician referral for screening
      colonoscopy. Education materials focused on specific sociodemographic segments
      and targeted communication campaigns need to be developed to encourage screening.

PMID- 18074185
TI  - Delayed visceral arterial hemorrhage following Whipple's procedure: minimally
      invasive treatment with covered stents.
AB  - BACKGROUND: Delayed visceral arterial hemorrhage caused by inflammatory vessel
      erosion represents a rare but life-threatening complication after pancreatic head
      resection. Therapeutic options include reoperation or endovascular minimally
      invasive techniques such as embolization or stent graft placement. The present
      article describes our experiences with implantation of newly developed low
      profile stent grafts. METHODS: The findings of four patients with delayed
      visceral arterial hemorrhage are described. All patients were treated with
      placement of low-profile stent grafts. The patients' medical records,
      radiological reports, and images were retrospectively reviewed. Technical success
      was defined as immediate cessation of hemorrhage. Clinical success was defined as
      hemodynamic stability. RESULTS: A total of seven stent grafts were implanted in
      four arteries. In detail, one stent graft was placed in the splenic artery of the
      first and second patients. In the third patient one stent graft was initially
      implanted in the common hepatic artery. The patient developed recurrent
      hemorrhages of the common hepatic artery, treated one time surgically and two
      times by deployment of a second and third stent graft. In the fourth patient two
      stent grafts were placed in the proper hepatic artery. Technical and clinical
      success was achieved at every procedure. Apart from recurrent hemorrhage of
      patient No. 3 there were no major complications. CONCLUSIONS: Minimally invasive
      therapy using low-profile stent grafts is an effective and safe procedure for the
      treatment of delayed visceral arterial hemorrhage following Whipple's procedure.
      The technique is a promising alternative to standard procedures such as surgical
      repair or embolization.

PMID- 18074186
TI  - Intraabdominal schwannomas: a single institution experience.
AB  - INTRODUCTION: Intraabdominal schwannomas are rare, benign tumors. This study
      presents a single institution experience with 12 such tumors. METHODS: Between
      1991 to 2006, 12 patients with a pathologically proven intraabdominal schwannoma
      were identified from a series of 216 mesenchymal tumors and were reviewed
      retrospectively. RESULTS: There were nine females and three male patients with a
      median age of 58 years (range 35-88 years). Eleven patients were symptomatic, and
      the tumors were located in the stomach (n = 8), jejunum, colon, rectum, and
      lesser sac. Multiple preoperative investigations including endoscopies with
      biopsies and computed tomography (CT) scans were performed, but none yielded a
      correct definitive preoperative diagnosis. The median tumor size was 52 mm (range
      18-95 mm). Pathological examination demonstrated the 11 gastrointestinal tract
      (GIT) schwannomas to be solid homogenous tumors, which were highly cellular and
      were composed of spindle cells with positive staining for S100 protein. The
      pathological appearance of the lesser sac schwannoma was distinct as it
      demonstrated cystic degeneration with hemorrhage and Antoni A and B areas on
      microscopy typical of soft tissue schwannomas. All 12 patients were disease-free
      at a median follow-up of 22 months (range 1-120 months). CONCLUSION:
      Intraabdominal schwannomas are rare tumors, which are most frequently located
      within the GIT. GIT schwannomas are difficult if not impossible to diagnose
      preoperatively as endoscopic and radiologic findings are nonspecific. The
      treatment of choice is complete surgical excision because of diagnostic
      uncertainty, and the long-term outcome is excellent as these lesions are
      uniformly benign.

PMID- 18074187
TI  - Decreased surfactant protein B expression in mice derived completely from
      embryonic stem cells.
AB  - ES mice that are derived completely from embryonic stem (ES) cells can be
      obtained by tetraploid embryo complementation. Many neonate ES mice die because
      of respiratory distress, but it is not clear what contributes to the phenomenon.
      Using five microsatellite DNA markers, we confirmed that our ES mice were
      completely derived from ES cells and contained no tetraploid component. The
      neonatal ES mice that exhibited respiratory distress were tested for surfactant
      protein B (SP-B) expression by Western blotting. These mice had no SP-B
      expression, and even apparently healthy adult ES mice had decreased SP-B levels
      and aberrant SP-B phenotypes. These data suggest that the expression of SP-B
      protein is an important factor in the survival of ES mice to term and adulthood.

PMID- 18074188
TI  - Establishment and conditions for growth and differentiation of a myoblast cell
      line derived from the semimembranosus muscle of newborn piglets.
AB  - To establish an adequate model to study the proliferation and differentiation of
      porcine skeletal muscle in response to bioactive compounds, a pool of satellite
      cells was derived from the semimembranosus muscle (SM) of newborn piglets using a
      Percoll gradient centrifugation. The final yield amounted to 4.1 x 10(6) cells/g
      muscle tissue. The percentage of muscle satellite cells has been determined by
      immunostaining for desmin and subsequent fluorescence analysis by flow cytometry,
      which revealed 95% of desmin-positive cells. For proliferation studies, satellite
      cell born myoblasts were seeded in gelatin-coated 96-well microplates at about 5
      x 10(3) cells per well. Cells were grown for 1 day in MEMalpha plus 10% fetal
      bovine serum (FBS) and 10% horse serum (HS), followed by 2 d cultivation in serum
      free growth medium. For differentiation studies, myoblasts were cultured in
      matrigel-coated 24-well plates for 4 d with growth medium containing 10% FBS and
      10% HS. At 80% confluence, cells were grown for 24 h in medium plus 10% FBS and 1
      microM insulin to initiate differentiation. Subsequently, the cells were cultured
      in serum-free differentiation medium (SFDM) for 3 d to form myotubes. Cultures
      reached a maximum fusion rate of approximately 20% after 96 h. By establishing
      this culture system, we provide an advanced and appropriate in vitro model to
      study porcine skeletal muscle cell growth and differentiation including the
      responses to various bioactive compounds.

PMID- 18074189
TI  - Effects of weight loss on bone status after bariatric surgery: association
      between adipokines and bone markers.
AB  - BACKGROUND: The prevalence of overweight and obesity is increasing dramatically
      worldwide. As a consequence, bariatric surgery for morbid obesity is in constant
      development. Although bariatric surgery has proven its efficiency at achieving
      weight loss and correcting comorbidities, it may cause vitamin deficiencies and
      subsequent complications. The goal of this review is to assess the impact of
      obesity surgery on bone metabolism and to analyze the underlying mechanisms and
      relationships with adipokines. Our review focuses on gastric banding, vertical
      banded gastroplasty, and gastric bypass. METHODS: The articles were located via
      PubMed database, using the key words "bariatric surgery," "weight loss," "bone
      loss," and "bone metabolism" and published until May 2006. RESULTS: Five main
      studies were reviewed concerning gastric banding and six concerning Roux-en-Y
      gastric bypass. An early increase in bone markers (formation and resorption) is
      constantly found, prevailing on bone resorption, and resulting in early bone
      loss. CONCLUSION: According to the few studies available, bone loss frequently
      occurs after bariatric surgery and particularly in a more pronounced way after
      gastric bypass, but its clinical significance is still under discussion. In
      addition, the physiopathology of these changes remains unclear, but could
      implicate adipokines such as leptin and adiponectin.

PMID- 18074191
TI  - Using the concept of Chou's pseudo amino acid composition to predict protein
      subcellular localization: an approach by incorporating evolutionary information
      and von Neumann entropies.
AB  - The rapidly increasing number of sequence entering into the genome databank has
      called for the need for developing automated methods to analyze them. Information
      on the subcellular localization of new found protein sequences is important for
      helping to reveal their functions in time and conducting the study of system
      biology at the cellular level. Based on the concept of Chou's pseudo-amino acid
      composition, a series of useful information and techniques, such as residue
      conservation scores, von Neumann entropies, multi-scale energy, and weighted auto
      correlation function were utilized to generate the pseudo-amino acid components
      for representing the protein samples. Based on such an infrastructure, a
      hybridization predictor was developed for identifying uncharacterized proteins
      among the following 12 subcellular localizations: chloroplast, cytoplasm,
      cytoskeleton, endoplasmic reticulum, extracell, Golgi apparatus, lysosome,
      mitochondria, nucleus, peroxisome, plasma membrane, and vacuole. Compared with
      the results reported by the previous investigators, higher success rates were
      obtained, suggesting that the current approach is quite promising, and may become
      a useful high-throughput tool in the relevant areas.

PMID- 18074192
TI  - Real time reading in mammography breast screening.

PMID- 18074193
TI  - Brain perfusion CT: principles, technique and clinical applications.
AB  - The imaging of brain haemodynamics and its applications are generating growing
      interest. By providing quantitative measurements of cerebral blood flow (CBF) and
      cerebral blood volume (CBV), dynamic perfusion computed tomography (p-CT) allows
      visualisation of cerebral autoregulation mechanisms and represents a fast,
      available and reliable imaging option for assessing cerebral perfusion. Thanks to
      its feasibility in emergency settings, p-CT is considered most useful, in
      combination with CT angiography, in acute ischaemic patients, as it is able to
      provide a fast and noninvasive assessment of cerebral perfusion impairment. In
      addition, p-CT can play a diagnostic role in other types of cerebrovascular
      disease to assess functional reserve, and in intracranial neoplasms, where it has
      a role in diagnosis, grading, biopsy guidance, and follow-up during treatment.
      This article illustrates the principles, technique and clinical applications of p
      CT cerebral perfusion studies.

PMID- 18074194
TI  - Contrast-enhanced ultrasonography (voiding urosonography) of vesicoureteral
      reflux: state of the art.
AB  - Three methods are currently used to identify vesicoureteral reflux (VUR) in
      children, namely, radiographic voiding cystourethrography, radionuclide voiding
      cystography and, more recently, echo-enhanced voiding urosonography (VUS). Recent
      advances in tissue-harmonic and contrast-specific imaging techniques, together
      with the development of second-generation contrast agents, have improved the
      potential of ultrasonography both in the diagnosis and grading of VUR in
      children. Today, VUS is able to accurately assess the grade of reflux and the
      state of the urethra, previously considered fundamental limitations to the
      extensive use of this technique. The aim of our paper is to review the role of
      ultrasonography in the diagnosis of VUR, from the initial experiences up to the
      recent use of second-generation microbubbles combined with contrast-specific low
      mechanical-index software. We discuss the advantages and limits of VUS with
      respect to radiographic and radionuclide imaging in the light of an analysis of
      the most recent literature, and we described the new VUS study technique using
      second-generation contrast media. Growing requests by paediatric nephrologists
      and surgeons require that even general radiologists become familiar with this
      technique.

PMID- 18074195
TI  - Diffusion-weighted magnetic resonance imaging in the evaluation of renal
      function: a preliminary study.
AB  - PURPOSE: Magnetic resonance diffusion-weighted imaging (MR-DWI) is useful to
      assess proton motion by the computation of an apparent diffusion coefficient
      (ADC). This property could be used to assess renal damage, with special regard to
      unilateral dysfunction. The aim of this study was to estimate the correlation
      between ADC and the stage of chronic renal failure (CRF) using a spin-echo echo
      planar imaging (SE-EPI) sequence with the sensitivity encoding (SENSE) technique.
      MATERIALS AND METHODS: Fourteen patients (nine men and five women, mean age 49
      years, range 22-66 years) underwent an MR examination on a 1.5-T system. Seven
      patients had a history of hypertension or CRF, one had Takayasu disease and one
      had nephrovascular hypertension. Five subjects without known kidney disease were
      used as controls. The glomerular filtration rate (GFR) assessed by Cockcroft
      Gault's equation was used as a functional marker. The imaging protocol consisted
      of T1- and T2-weighted sequences followed by a SE-EPI acquisition with a
      diffusion gradient of 600 s/mm(2) and SENSE factor 2 and pixel-by-pixel ADC map
      reconstruction. In five patients, the SE-EPI-DWI sequence was repeated after i.v.
      administration of 1 mg of furosemide. RESULTS: ADC was of 2.44+/-0.24 x 10(-3)
      mm(2)/s in patients with normal GFR and of 2.05+/-0.33 x 10(-3) mm(2)/s (p<0.05)
      in subjects with altered GFR; a significant difference was found between stage
      III and IV (p<0.01), whereas no differences were found between stage I and II
      (p=0.27) and between stage II and III (p=0.39). A good correlation was found
      between GFR and ADC (r=0.79; p<0.01), with no significant change after furosemide
      administration (p=0.7). CONCLUSIONS: DWI is a feasible MR technique for assessing
      renal damage. Further studies with scintigraphic correlation are needed to
      confirm these results and to establish reference values for this imaging
      technique.

PMID- 18074196
TI  - Open-source, low-cost, high-reliability solutions for digital imaging systems:
      example of a "dicom router".
AB  - PURPOSE: The purpose of this article is to illustrate a case where acquisition of
      digital imaging know-how by a modern radiotherapy division has helped to solve a
      technical problem while allowing substantial savings through the use of free and
      open-source resources. The problem was related to the necessity to route, with
      complex policies, the images produced by different digital imaging and
      communications in medicine (DICOM) sources within the department or in other
      divisions and/or hospitals. MATERIALS AND METHODS: The problem was solved by
      using completely free, well-tested and stable technologies (PHP, Apache, MySQL,
      DCMTK OFFIS, Red Hat Linux 9A and Linux Fedora Core 4) and low-cost hardware to
      contain costs. In the development, we also considered integration of the routed
      images with the existing electronic clinical records. RESULTS: The system
      developed, called the dicom router, implemented two kinds of routing: manual and
      automatic, both oriented to link the images acquired with the existing electronic
      clinical records. System stability was enhanced in a second phase by using a low
      cost hardware redundancy solution. The system has now been operating for 1 year
      and has proved the value of the technologies used. CONCLUSIONS: The need to
      operate with more than one provider creates a series of integration issues, so
      that it becomes economically appealing to acquire internally the knowledge needed
      to interact more precisely with providers of big information technology (IT)
      solutions. This need is well catered for by open-source technologies, which are
      well documented and available to everyone. By using them, in-house IT technicians
      are able to implement valuable technical solutions for small-to medium-sized
      informatization problems, which would otherwise remain unsolved except with great
      economic efforts.

PMID- 18074197
TI  - CT enteroclysis: multidetector technique (MDCT) versus single-detector technique
      (SDCT) in patients with suspected small-bowel Crohn's disease.
AB  - PURPOSE: This study was done to evaluate the diagnostic role of enteroclysis with
      multidetector computed tomography (MDCT) and single-detector CT (SDCT) in
      patients affected by small-bowel Crohn's disease. MATERIALS AND METHODS: Forty
      five patients underwent abdominal SDCT (n=20) or 16-row MDCT (n=25) after
      administration of methylcellulose by nasojejunal tube. Each examination was
      assessed for small-bowel distension and site and characteristics of the diseased
      loops. The two CT techniques were then compared. Results were compared with
      double-contrast enteroclysis performed in all patients and with ileoscopy
      performed in 28 patients. RESULTS: In comparison with double-contrast
      enteroclysis, sensitivity, specificity and diagnostic accuracy were 90%, 71% and
      89% for SDCT and 92%, 83% and 90% for MDCT. Ileoscopy confirmed the absence of
      disease in five patients and the presence of Crohn's disease in 20. Compared with
      SDCT, MDCT reduced scanning time and respiratory artefacts and permitted better
      multiplanar reconstructions. CONCLUSIONS: MDCT is superior to SDCT because it
      allows a better spatial resolution and improves depiction of the pathological
      patterns of Crohn's disease.

PMID- 18074198
TI  - Accuracy of CT-guided transthoracic needle biopsy of lung lesions: factors
      affecting diagnostic yield.
AB  - PURPOSE: This study was performed to analyse the variables affecting the
      diagnostic accuracy of computed tomography (CT)-guided transthoracic needle
      biopsy of pulmonary lesions. MATERIALS AND METHODS: A retrospective study of 612
      consecutive procedures with confirmed final diagnoses was undertaken. Benign and
      malignant needle biopsy results were compared with final outcomes to determine
      diagnostic accuracy. A statistical analysis of factors related to patient
      characteristics, lung lesions and biopsy technique was performed to determine
      possible influences on diagnostic yield. A p value less than 0.05 was interpreted
      as statistically significant. RESULTS: There were 508 (83%) malignant and 104
      (17%) benign lesions. Sensitivity, specificity, positive predictive value,
      negative predictive value and accuracy for a diagnosis of malignancy were 90.2%,
      99.0%, 99.8%, 67.3% and 91.7%, respectively. Overall diagnostic accuracy was
      83.3%. Variables affecting diagnostic accuracy were the final diagnosis (benign
      67%, malignant 92%; p<0.001) and lesion size (lesions<1.5 cm 68%, lesions 1.5-5.0
      cm 87%, lesions>5 cm 78%; p<0.05). CONCLUSIONS: In CT-guided transthoracic needle
      biopsy, the final diagnosis and lesion size affect diagnostic accuracy: benign
      lung lesions and lesions smaller than 1.5 cm or larger than 5.0 cm in diameter
      provide lower diagnostic yield.

PMID- 18074199
TI  - Uncommon causes of tracheobronchial stenosis and wall thickening: MDCT imaging.
AB  - Some uncommon diseases may involve the central airways focally or diffusely.
      These include Wegener's granulomatosis, relapsing polychondritis,
      tracheobronchopathia osteochondroplastica, amyloidosis, papillomatosis,
      rhinoscleroma, sarcoidosis and tuberculosis. Related computed tomography (CT)
      findings essentially include calcifications, luminal stenosis, wall thickening
      and nodules. The purpose of this paper is to help refine the differential
      diagnosis among these diseases through the use of multidetector CT (MDCT)
      imaging.

PMID- 18074200
TI  - Multidetector CT and coronary artery bypass grafts.
AB  - The aim of this review is to provide--starting from anatomical, surgical and
      pathophysiological data--elements for evaluating the status of coronary artery
      bypass grafts with multidetector computed tomography (CT), taking into
      consideration the most common conduits used (left and right internal mammary
      arteries, saphenous vein, radial artery, gastroepiploic artery) and early and
      late complications (stenosis or obstruction, vasospasm, aneurysms and
      pseudoaneurysms, malposition). Some of the major problems regarding the
      examination technique and image analysis are also discussed. Finally, we offer
      general guidelines for reporting the examination results.

PMID- 18074202
TI  - Increasing the dissolution rate of itraconazole processed by gas antisolvent
      techniques using polyethylene glycol as a carrier.
AB  - PURPOSE: The purpose of this study was to increase the dissolution rate of the
      poorly water soluble, antifungal drug Itraconazole. METHODS: Itraconazole was
      successfully micronized using both the gas antisolvent (GAS) and aerosol solvent
      extraction systems (ASES) using Acetone as the solvent. The affects of operating
      conditions such as temperature, pressure and solvent choice on variables such as
      morphology, particle size and dissolution were investigated. The influence of
      temperature in the range 25 to 40 degrees C and pressure between 90 and 190 bar
      were investigated. RESULTS: Solvent choice was found to have the largest affect
      on particle production, with acetone found to be the optimal solvent choice when
      compared with dimethyl formamide (DMF), tetrahydrofuran (THF) and dichloromethane
      (DCM). Itraconazole particles with an average particle size of 6.9 microm were
      formed at the optimal ASES processing conditions of 40 degrees C and 190 bar.
      More significantly, in the first 100 minutes of dissolution 71.1% of the dense
      gas processed itraconazole was dissolved compared with 52.5% of Sporonox (the
      commercially available formulation) and 14.6% of the unprocessed material.
      Additional studies demonstrated that the formation of an itraconazole/PEG
      composite resulted in a 6-fold increase in dissolution rate in the first 100 min,
      to 89.8%, when compared to the unprocessed material. CONCLUSIONS: Using ASES,
      microparticles of itraconazole were produced with an increased dissolution rate
      compared with raw material and commercially available product.

PMID- 18074204
TI  - A new enhanced oscillating chemiluminescence system with increased
      chemiluminescence intensity and oscillation time.
AB  - Oscillating chemical reactions are complex systems, involving a large number of
      chemical species. In an oscillating chemical reaction, some species, usually a
      reaction intermediate, exhibit fluctuation in its concentration. In this report,
      oscillating chemiluminescence produced by the addition of thiosemicarbazide (TSC)
      to the oscillating system H(2)O(2)-KSCN-CuSO(4)-NaOH was investigated using
      luminometry method. The effects of complexing agents, triethylenetetramine (TETA)
      and D-penicillamine, on the behavior of the oscillating system were investigated.
      Moreover, the influence of non-aqueous solvents, dimethyl sulfoxide (DMSO),
      nitromethane and acetonitrile, was studied. In the presence of solvents with high
      protophility, the chemiluminescence (CL) intensity was increased (sevenfold), the
      light emitting and oscillating time was enhanced by threefold. In addition, the
      effect of presence of non-ionic, cationic, and anionic surfactants was
      investigated. Non-ionic surfactant increased the intensity of the oscillating CL
      reaction by 4.5-fold.

PMID- 18074203
TI  - Synthesis, characterization, DNA-binding properties of the Ln(III) complexes with
      6-hydroxy chromone-3-carbaldehyde-(4'-hydroxy) benzoyl hydrazone.
AB  - 6-Hydroxy chromone-3-carbaldehyde-(4'-hydroxy) benzoyl hydrazone (L) and its Ln
      (III) complexes, [Ln = La, Nd, Eu and Tb] have been prepared and characterized on
      the basis of elemental analyses, molar conductivities, mass spectra, (1)H NMR,
      thermogravimetry/differential thermal analysis (TG-DTA), UV-vis spectra,
      fluorescence spectra and IR spectra. The formula of the complex is [Ln
      L.(NO(3))(2)].NO(3). Spectrometric titration, ethidium bromide displacement
      experiments and viscosity measurements indicate that Eu (III) complex bind with
      calf-thymus DNA, presumably via an intercalation mechanism. The intrinsic binding
      constant of Eu (III) with DNA was 2.48 x 10(5) M(-1) through fluorescence
      titration data.

PMID- 18074201
TI  - RNAi for treating hepatitis B viral infection.
AB  - Chronic hepatitis B virus (HBV) infection is one of the leading causes of liver
      cirrhosis and hepatocellular carcinoma (HCC). Current treatment strategies of HBV
      infection including the use of interferon (IFN)-alpha and nucleotide analogues
      such as lamivudine and adefovir have met with only partial success. Therefore, it
      is necessary to develop more effective antiviral therapies that can clear HBV
      infection with fewer side effects. RNA interference (RNAi), by which a small
      interfering RNA (siRNA) induces the gene silence at a post-transcriptional level,
      has the potential of treating HBV infection. The successful use of chemically
      synthesized siRNA, endogenous expression of small hairpin RNA (shRNA) or microRNA
      (miRNA) to silence the target gene make this technology towards a potentially
      rational therapeutics for HBV infection. However, several challenges including
      poor siRNA stability, inefficient cellular uptake, widespread biodistribution and
      non-specific effects need to be overcome. In this review, we discuss several
      strategies for improving the anti-HBV therapeutic efficacy of siRNAs, while
      avoiding their off-target effects and immunostimulation. There is an in-depth
      discussion on the (1) mechanisms of RNAi, (2) methods for siRNA/shRNA production,
      (3) barriers to RNAi-based therapies, and (4) delivery strategies of siRNA for
      treating HBV infection.

PMID- 18074205
TI  - Application of the Doehlert design to optimize the signal obtained in
      photochemically induced fluorescence for the determination of eight phenylureas.
AB  - This work describes the optimization of a photochemically induced method for the
      detection of eight phenylureas has been developed by response surface methodology
      (RSM). These pesticides do not show native fluorescence but they were photolyzed
      into strongly fluorescent photoproducts under UV irradiation. The effect of the
      main variables affecting the yield of the photoderivatization reaction, and hence
      the fluorescence intensity, such as solvent, UV irradiation time and pH were
      optimized for each pesticide. A Doehlert design was applied in order to obtain
      maximum intensity fluorescence using response surface methodology. In general, a
      maximum was found for all pesticides using MeOH as organic solvent, except for
      diuron, whereas the effect of pH and irradiation time was different, according to
      each pesticide. Finally, the addition of beta-cyclodextrin upon the
      photochemically induced fluorescence intensity was investigate. The fluorescence
      intensity was only improved for monolinuron at a concentration of 4 x 10(-3) M of
      beta-cyclodextrin.

PMID- 18074206
TI  - Dictyostelium extracellular vesicles containing hoechst 33342 transfer the dye
      into the nuclei of living cells: a fluorescence study.
AB  - Cells of the eukaryotic unicellular microorganism Dictyostelium discoideum are
      constitutively resistant to vital staining of their nuclei by the DNA-specific
      dye Hoechst 33342. By studying the mechanisms of this resistance, we evidenced
      that these cells expel vesicles containing the dye for detoxification (Tatischeff
      et al., Cell Mol Life Sci, 54: 476-87, 1998). The question to be addressed in the
      present work is the potential use of these extracellular vesicles as a biological
      drug delivery tool, using Hoechst 33342 as a model of a DNA-targeting drug. After
      cell growth with or without the dye, vesicles were prepared from the cell-free
      growth medium by differential centrifugation, giving rise to two types of
      vesicles. Negative staining electron microscopy showed their large heterogeneity
      in size. Using fluorescence techniques, data were obtained on the dye loading and
      its environment inside the vesicles. By UV video-microscopy, it was demonstrated
      that the dye-containing vesicles were able to deliver it into the nuclei of naive
      Dictyostelium cells, thus overcoming their constitutive resistance to the free
      dye. A vesicle-mediated dye-transfer into the nuclei of living human leukaemia
      multidrug resistant K562r cells was also observed.

PMID- 18074207
TI  - Lost in translation: bibliotherapy and evidence-based medicine.
AB  - Evidence-based medicine's (EBM) quantitative methodologies reflect medical
      science's long-standing mistrust of the imprecision and subjectivity of ordinary
      descriptive language. However, EBM's attempts to replace subjectivity with
      precise empirical methods are problematic when clinicians must negotiate between
      scientific medicine and patients' experience. This problem is evident in the case
      of bibliotherapy (patient reading as treatment modality), a practice widespread
      despite its reliance on anecdotal evidence. While EBM purports to replace such
      flawed practice with reliable evidence-based methods, this essay argues that its
      aversion to subjective language prevents EBM from effectively evaluating
      bibliotherapy or making it amenable to clinical and research governance.

PMID- 18074208
TI  - The relationship of body size to participation and success in a fruits and
      vegetables intervention among low-income women.
AB  - We examined participation and dietary change among women participants in a
      community-based nutrition education program, to determine whether intervention
      results differed by participant body size. Four dietary indicators (daily
      servings of fruits and vegetables, total calories, calories from fat, and Healthy
      Eating Index score) were assessed from 24-h recalls taken before, immediately
      after, and 4 months after a seven-session nutritional education program, from 156
      African-American women age 20-50, in Washington, D.C. public housing. Knowledge,
      attitudes and practices related to nutritional behavior change were collected at
      three time points as well. Random effect models were used to examine dietary
      patterns, and compare change by body size and class attendance. Results showed
      that obese women (BMI > or = 30) had more psychosocial barriers to dietary change
      and poorer baseline diets, but stronger program attendance. Post-intervention,
      both groups consumed approximately 250 fewer calories and 2.5% fewer calories
      from fat. At follow-up, non-obese women consumed significantly fewer calories;
      obese women consumed significantly fewer calories from fat, and showed
      significant improvement in HEI. Given the prevalence of obesity in low resource
      communities, nutritional interventions should tailor strategies to participant
      body size and related psychosocial needs.

PMID- 18074209
TI  - The implementation and utility of fire incident reporting systems: the Delaware
      experience.
AB  - Fires and burns are the fifth most common cause of unintentional injury deaths in
      the United States. To address fires and fire deaths, the National Fire Data
      Center (NFDC) established the National Fire Incident Reporting System (NFIRS) as
      a surveillance system for fires. Delaware implemented NFIRS as the Delaware Fire
      Incident Reporting System (DFIRS), and is currently capturing all fires reported
      in the system. The objectives of this study are to: 1) understand the
      implementation of DFIRS; 2) analyze data from DFIRS to describe fire incidents;
      and 3) inform other states' fire surveillance efforts. We interviewed Delaware
      State Fire Marshal's Office personnel to understand the implementation of DFIRS
      and analyzed DFIRS data from May 2003 to December 2004 to examine data
      completeness, and characteristics of fires, smoke alarms, and fire injuries and
      deaths. DFIRS captures 100% of Delaware fires reported to fire departments. Data
      completeness for the fields examined ranged from 33% to 100%. Fires in which
      smoke alarms alerted occupants were significantly less likely to result in injury
      or death than fires in which smoke alarms did not. DFIRS has the potential to
      serve as a valuable fire prevention and fire analysis tool. For DFIRS to reach
      its full potential as a surveillance system, increased attention to data
      completeness is necessary.

PMID- 18074210
TI  - pH dependence of the isomerase activity of protein disulfide isomerase: insights
      into its functional relevance.
AB  - The isomerase efficacy of the oxidoreductase, protein disulfide isomerase (PDI),
      has been examined by a simple method. Using this technique, the pH-dependence of
      relative efficiency of isomerization reactions by PDI has been evaluated and its
      impact on a key structure-forming step in the oxidative folding pathway of a
      model protein determined. Results reveal that PDI has a greater relative impact
      on thiol-disulfide reshuffling (isomerization) reactions and consequently the
      structure-forming step in oxidative folding at pH 7, as opposed to pH's 8 and 9.
      These results suggest that PDI, which possesses an anomalously low thiol pKa, is
      fine-tuned to catalyze oxidative folding in the lumen of the endoplasmic
      reticulum where the ambient pH of approximately 7 would otherwise retard
      thioldisulfide exchange reactions and hinder acquisition of the native fold. The
      pH-dependent impact on isomerization catalysis has important implications for the
      development of synthetic chaperones for in vivo and in vitro applications.

PMID- 18074211
TI  - Homology modeling of hemagglutinin/protease [HA/P (vibriolysin)] from Vibrio
      cholerae: sequence comparision, residue interactions and molecular mechanism.
AB  - Vibrio cholerae produces a zinc-containing and calcium-stabilized soluble
      hemagglutinin/protease, which has been earlier shown to have the ability to
      cleave several physiologically important substrates including mucin, fibronectin
      and lactoferin. This study presents homology modeling of hemagglutinin/protease
      (vibriolysin) from Vibrio cholerae in the presence of inhibitor HPI [N-(1-carboxy
      3-phenylpropyl)-phenylalanyl-alpha-aspargine]. The 3D structure was predicted
      based on its sequence homology with Pseudomonas aeruginosa elastase (PAE).
      Comparison of the 3D structures of PAE and HA/P reveals a remarkable similarity
      having a conserved alpha + beta domain. The inhibitor shows similar binding
      features as seen in other metalloproteases of M4 peptidase family. The study also
      highlights the key catalytic residues as well as the residues at the S1 and S1'
      binding sub-sites. The similarities between the two proteins provide support for
      the hypothesis that the two enzymes have similar three-dimensional structures and
      a common mechanism of action. The fact that both enzymes are secreted as zinc
      containing proteases, led us to further hypothesize that they may play similar
      role in pathogenesis.

PMID- 18074212
TI  - Evidence for impairments in using static line drawings of eye gaze cues to orient
      visual-spatial attention in children with high functioning autism.
AB  - We examined the ability to use static line drawings of eye gaze cues to orient
      visual-spatial attention in children with high functioning autism (HFA) compared
      to typically developing children (TD). The task was organized such that on valid
      trials, gaze cues were directed toward the same spatial location as the
      appearance of an upcoming target, while on invalid trials gaze cues were directed
      to an opposite location. Unlike TD children, children with HFA showed no
      advantage in reaction time (RT) on valid trials compared to invalid trials (i.e.,
      no significant validity effect). The two stimulus onset asynchronies (200 ms, 700
      ms) did not differentially affect these findings. The results suggest that
      children with HFA show impairments in utilizing static line drawings of gaze cues
      to orient visual-spatial attention.

PMID- 18074213
TI  - Stem pitting and seedling yellows symptoms of Citrus tristeza virus infection may
      be determined by minor sequence variants.
AB  - The isolates of Citrus tristeza virus (CTV), the most destructive viral pathogen
      of citrus, display a high level of variability. As a result of genetic bottleneck
      induced by the bud-inoculation of CTV-infected material, inoculated seedlings of
      Citrus wilsonii Tanaka displayed different symptoms. All successfully grafted
      plants showed severe symptoms of stem pitting and seedling yellows, while plants
      in which inoculated buds died displayed mild symptoms. Since complex CTV
      population structure was detected in the parental host, the aim of this work was
      to investigate how it changed after the virus transmission, and to correlate it
      with observed symptoms. The coat protein gene sequence of the predominant
      genotype was identical in parental and grafted plants and clustered to the
      phylogenetic group 5 encompassing severe reference isolates. In seedlings
      displaying severe symptoms, the low-frequency variants clustering to other
      phylogenetic groups were detected, as well. Indicator plants were inoculated with
      buds taken from unsuccessfully grafted C. wilsonii seedlings. Surprisingly, they
      displayed no severe symptoms despite the presence of phylogenetic group 5 genomic
      variants. The results suggest that the appearance of severe symptoms in this case
      is probably induced by a complex CTV population structure found in seedlings
      displaying severe symptoms, and not directly by the predominant genomic variant.

PMID- 18074214
TI  - Motherhood induces and maintains behavioral and neural plasticity across the
      lifespan in the rat.
AB  - Maternal behavior is multidimensional, encompassing many facets beyond the direct
      care of the young. Formerly unfamiliar activities are required of the mother.
      These include behaviors such as retrieving, grouping, crouching-over, and licking
      young, and protecting them against predators, together with enhancements in other
      behaviors, such as nest building, foraging, and aggression (inter/intra-species,
      predatory, etc.). When caring for young, the mother must strike a seemingly lose
      lose bargain: leave the relative safety of the nest and her helpless offspring to
      forage for food and resources where predators await both mother and her
      vulnerable young, or remain entrenched and safe, thereby ensuring a slow and
      inexorable fate. Two predictions thus arise from this maternal cost-benefit
      ratio: first, there may be enhancements in behaviors on which the female relies,
      for example, predation and spatial ability, used for acquiring food and resources
      and for navigating her environment. Second, there may be reductions in the fear
      and anxiety inherent to the decision to leave the nest and to forage in an
      unforgiving environment where encounters with predators or reluctant/resistant
      prey await. There is overwhelming support for both hypotheses, with improvements
      in learning and memory accompanied by a diminution in stress responses and
      anxiety. The current review will examine the background for the phenomenon that
      is the maternal brain, and recent relevant data. In sum, the data indicate a
      remarkable set of changes that take place in the maternal (and, to a lesser
      extent, the paternal), brain, arguably, for the natural, simple but singular
      experience of reproduction.

PMID- 18074215
TI  - Eye color, hair color, blood type, and the rhesus factor: exploring possible
      genetic links to sexual orientation.
AB  - The present study sought to expand the limited evidence that sexual orientation
      is influenced by genetic factors. This was accomplished by seeking statistical
      differences between heterosexuals and homosexuals for four traits that are known
      to be genetically determined: eye color, natural hair color, blood type, and the
      Rhesus factor. Using a sample of over 7,000 U.S. and Canadian college students
      supplemented with additional homosexual subjects obtained through internet
      contacts, we found no significant differences between heterosexuals and
      homosexuals regarding eye color or hair color. In the case of blood type and the
      Rh factor, however, interesting patterns emerged. Heterosexual males and females
      exhibited statistically identical frequencies of the A blood type, while gay men
      exhibited a relatively low incidence and lesbians had a relatively high incidence
      (p < .05). In the case of the Rh factor, unusually high proportions of
      homosexuals of both sexes were Rh- when compared to heterosexuals (p < .06). The
      findings suggest that a connection may exist between sexual orientation and genes
      both on chromosome 9 (where blood type is determined) and on chromosome 1 (where
      the Rh factor is regulated).

PMID- 18074216
TI  - Genetic and environmental influences on 2D:4D finger length ratios: a study of
      monozygotic and dizygotic male and female twins.
AB  - Recent studies have shown significant sex differences in the pattern of 2D:4D
      finger length ratios in humans and several other mammalian species. In humans,
      these ratios are suggested to be negatively correlated with prenatal exposure to
      testosterone, positively correlated with prenatal estrogen, and exhibit sex
      specific patterns of association with sexually dimorphic clinical phenotypes.
      However, the relative contributions of genetic and environmental influences on
      digit ratios in men and women are currently unknown. Therefore, the purpose of
      the current study was to examine genetic and environmental influences on 2D:4D
      ratios in twins. Participants included 146 monozygotic (MZ) and 154 dizygotic
      (DZ) adult male and female twins participating in the Michigan State University
      Twin Study of Behavioral Adjustment and Development. Overall, biometric model
      fitting analyses indicated significant additive genetic and nonshared
      environmental influences on digit ratios. Findings suggest greater similarity
      between 2D:4D ratios in MZ relative to DZ twins that can be accounted for by
      genetic and nonshared environmental factors.

PMID- 18074217
TI  - Spatial ability and prenatal androgens: meta-analyses of congenital adrenal
      hyperplasia and digit ratio (2D:4D) studies.
AB  - Hormonal manipulations indicate that early androgens organize sex differences in
      spatial ability in laboratory rats. In humans, spatial ability is also sexually
      dimorphic, and information about the effects of prenatal androgens on spatial
      ability can be obtained from studies of congenital adrenal hyperplasia (CAH) and
      the ratio of the second and fourth finger lengths (2D:4D). CAH is characterized
      by prenatal overproduction of adrenal androgens and several lines of evidence
      suggest that 2D:4D reflects prenatal androgen exposure. Some studies have found
      that these proxy measures of prenatal androgens predict spatial ability, others
      have found no significant relationship, and yet others have obtained results in
      the opposite direction. In light of these mixed findings, we conducted meta
      analyses of published literature and unpublished results to determine if, across
      studies, either of these indicators of prenatal androgens predicts performance on
      spatial tasks that show a male advantage. In addition, we applied a trim and fill
      analysis to the data in search of asymmetry that might be an indication of
      publication bias. Results indicated that females with CAH perform better on these
      spatial tasks, and CAH males perform worse, than do controls. Little or no
      relationship exists between 2D:4D and spatial ability. Implications for possible
      hormonal contributions and the developmental timing of sex differences in spatial
      cognition are discussed.

PMID- 18074218
TI  - The brain as the engine of sex differences in the organization of movement in
      rats.
AB  - Sex differences in the kinematic organization of non-reproductive behavior are
      often relegated to byproducts of sex differences in body morphology. We review
      evidence showing not only that male and female rats organize their posture and
      stepping differently during a variety of actions, but that these differences
      arise from sex differences in the organization of movement in the central nervous
      system (CNS). Indeed, the expression and choice of sex-typical patterns of
      movement can be altered by CNS injury. The pattern of hormonal regulation of
      these sex differences is also not organized as commonly held theory would
      predict. As expected, males castrated shortly after birth are female-typical in
      their motor organization. Females ovariectomized at birth, however, are male
      typical in their patterns of movement. Thus, female-typical patterns of movement
      organization are not the default form, but rather are dependent on the effects of
      gonadal steroids to feminize the developing CNS. The implications of these
      findings are discussed with regards to our understanding of the evolution of sex
      differences in CNS anatomy and behavior both for animals and humans.

PMID- 18074219
TI  - Sex differences and sexual orientation differences in personality: findings from
      the BBC Internet survey.
AB  - Analyzing a large international data set generated by a BBC Internet survey, I
      examined sex differences and sexual orientation differences in six personality
      traits: extraversion, agreeableness, neuroticism, disagreeable assertiveness,
      masculine versus feminine occupational preferences (MF-Occ), and self-ascribed
      masculinity-femininity (Self-MF). Consistent with previous research, sex
      differences and sexual orientation differences were largest for MF-Occ and for
      Self-MF. In general, heterosexual-homosexual differences mirrored sex differences
      in personality, with gay men shifted in female-typical and lesbians in male
      typical directions. Bisexual men scored intermediate between heterosexual and gay
      men on MF-Occ; however, they were slightly more feminine than gay men on Self-MF.
      Bisexual women scored intermediate between heterosexual women and lesbians on
      both MF-Occ and Self-MF. Sex differences and sexual orientation differences in MF
      Occ, Self-MF, and other personality traits were consistent across five
      nations/world regions (the UK, USA, Canada, Australia/New Zealand, and Western
      Europe), thereby suggesting a biological component to these differences.

PMID- 18074220
TI  - Neurodevelopmental correlates of paraphilic sexual interests in men.
AB  - The etiology of anomalous, or paraphilic, sexual preferences in men is unclear
      although a growing literature points to their prenatal neurodevelopmental
      ontogenesis. The present study explored whether this was also apparent in a
      community sample of 200 heterosexual men by examining their sexual fantasies
      using the Wilson Sex Fantasy Questionnaire (WSFQ) and several demographic and
      somatic neurodevelopmental markers, including sibling sex composition,
      handedness, maternal and paternal age at birth, second to fourth finger length
      ratios, and fluctuating asymmetry of finger lengths and wrist widths. Responses
      to the WSFQ were used to quantify the extent of paraphilic interest by computing
      a variance-quotient (or VQ) previously shown to differentiate paraphilic from
      conventional heterosexual males. High paraphilic scorers had a significantly
      greater number of older brothers, higher right-hand 2D:4D, and a trend for lower
      Edinburgh Handedness Inventory (EHI) scores compared to low-paraphilic scorers.
      Correlational analysis revealed a significant positive association of VQ scores
      with number of older brothers and significant negative associations with number
      of younger brothers and EHI scores (elevated paraphilic interests were correlated
      with elevated non-right handedness). Correlations between VQ scores and other
      variables were not significant. It is suggested that processes such as
      developmental instability and maternal immunity may play a role in variant sexual
      preferences among otherwise healthy heterosexual men.

PMID- 18074221
TI  - Heritability of self-reported phobic fear.
AB  - Twin studies on fear and phobia suggest moderate genetic effects. However,
      results are inconclusive regarding the presence of dominant genetic effects and
      sex differences. Using an extended twin design, including male and female twins
      (n = 5,465) and their siblings (n = 1,624), we examined the genetic and
      environmental influences on blood-injury, social, and agoraphobic fear and
      investigated their interaction with sex and age. Data of spouses (n = 708) of
      twins were used to evaluate assortative mating for the three fear dimensions.
      Results showed that there was no assortative mating for blood-injury, social and
      agoraphobic fear. Resemblance between biological relatives could be explained by
      additive and non-additive genetic effects for blood-injury and agoraphobic fear
      in all participants, and social fear in participants aged 14-25 years. For social
      fear in participants aged 26-65 only additive genetic effects were detected.
      Broad-sense heritability estimates ranged from 36 to 51% and were similar for men
      and women.

PMID- 18074222
TI  - Genetic and environmental influences on the relation between attention problems
      and attention deficit hyperactivity disorder.
AB  - OBJECTIVE: The assessment of symptoms of ADHD in children is usually based on a
      clinical interview or a behavior checklist. The aim of the present study is to
      investigate the extent to which these instruments measure an underlying construct
      and to estimate the genetic and environmental influences on individual
      differences in ADHD. METHODS: Maternal ratings were collected on 10,916 twins
      from 5,458 families. Child Behavior Checklist (CBCL) ratings were available for
      10,018, 6,565, and 5,780 twins at the ages 7, 10, and 12, respectively. The
      Conners Rating Scale (4,887 twins) and the DSM interview (1,006 twins) were
      completed at age 12. The magnitude of genetic and environmental influences on the
      variance of the three measures of ADHD and the covariance among the three
      measures of ADHD was obtained. RESULTS: Phenotypic correlations range between .45
      and .77. Variances and covariances of the measurements were explained mainly by
      genetic influences. The model that provided the best account of the data included
      an independent pathway for additive and dominant genetic effects. The genetic
      correlations among the measures collected at age 12 varied between .63 and 1.00.
      CONCLUSIONS: The genetic overlap between questionnaire ratings and the DSM-IV
      diagnosis of ADHD is high. Clinical and research implications of these findings
      are presented.

PMID- 18074223
TI  - Comprehensive analysis of oncogenic effects of PIK3CA mutations in human mammary
      epithelial cells.
AB  - More than 20 different PIK3CA gene mutations were identified in breast cancer
      with different frequencies. Whether these breast cancer associated mutations have
      similar biological effects is largely unknown. In this study, we established a
      novel cell model using the lentivirus system to express 10 different PIK3CA genes
      (wild type and mutant) based on the human mammary epithelial cell MCF10A. We
      found that nine different PIK3CA mutants harbor different abilities to promote
      cell proliferation and EGF independent growth. In addition, most PIK3CA mutants
      (except for the wild type PIK3CA, the Q60K and the K111N mutants) had the ability
      to change the morphogenesis of the MCF10A cell in 3D Matrigel assay. Moreover,
      different PIK3CA mutants have different abilities to promote colony formation and
      cell invasion. We further observed that most of the PIK3CA mutants could activate
      p-AKT and p-p70-S6K in the absence of EGF stimulation. Finally, LY294002, a PI3K
      inhibitor, can effectively inhibit cell growth in cell lines with different
      PIK3CAs. Taken together, our results support the notion that different PIK3CA
      mutations differentially contribute to breast cancer transformation, and
      exploration of the therapeutic application of these mutations will benefit breast
      cancer patients with the PIK3CA mutations.

PMID- 18074224
TI  - Concise chemical synthesis of a tetrasaccharide repeating unit of the O-antigen
      of Hafnia alvei 10457.
AB  - Concise chemical synthesis of a tetrasaccharide repeating unit of the O-antigen
      of Hafnia alvei 10457 is reported. Construction of the tetrasaccharide as its 4
      methoxyphenyl glycoside was achieved by condensation of less abundant
      monosaccharide units such as, D-galactofuranose, N-acetyl-D-galactosamine and N
      acetylneuraminic acid. The synthetic strategy consists of the preparation of
      suitably protected required monosaccharide intermediates from the commercially
      available reducing sugars and high yielding glycosylation reactions.

PMID- 18074225
TI  - The detergent-insoluble microdomains, rafts, can be used as an effective
      immunogen.
AB  - Detergent-insoluble microdomains, or rafts, act as a platform to transduce
      signals from the extracellular space into the cytoplasm. In the process of
      developing monoclonal antibodies against raft molecules for the purpose of
      studying the molecular mechanism of raft-mediated signaling, we observed the
      uniqueness and certain advantages of immunization with rafts. Simple subcutaneous
      injection of mice with a phosphate-buffered saline (PBS) suspension of rafts
      without mixing with Freund's adjuvant made it possible to increase the titer of
      antiserum reacting with raft components. Interestingly, injection of rafts
      prepared from certain specific cell lines induced monoglycolipid-specific
      antibodies. Furthermore, antibodies were produced by raft-immunization of even
      syngeneic mice. Our findings suggest that this phenomenon does not represent a
      breakdown of immunological self-tolerance, but typical immune reactions
      accompanying the class switch from IgM antibodies to IgG antibodies.

PMID- 18074227
TI  - Memories of Sam Wieand.

PMID- 18074228
TI  - Therapist attitudes and beliefs relevant to client dropout revisited.
AB  - This study replicates a survey conducted in the 1980s that examined therapist
      attitudes and beliefs relevant to client dropout. A revamped questionnaire
      modelled on the original was completed by 92% of therapists employed in the
      outpatient counselling arm of an alcohol and other drug treatment service. This
      questionnaire sought therapist perceptions of treatment length and client dropout
      as well as their preferred length of treatment engagement. Responses were then
      contrasted with known service attendance norms. As with the previous study, the
      results suggest therapists typically expect and prefer treatment of a
      considerably longer duration than the service mean and underestimate the rate of
      client dropout.

PMID- 18074226
TI  - Noninvasive imaging of apoptosis in cardiovascular disease.
AB  - Recent advances in molecular imaging have permitted the noninvasive imaging of
      apoptosis, a critical process underlying the pathogenesis of many diseases of the
      cardiovascular system including atherosclerotic vascular disease, myocardial
      ischemia and reperfusion injury, chronic heart failure, myocarditis, and cardiac
      allograft rejection. Multiple molecular targets including phosphatidylserine,
      phosphatidylinositol 3-kinase, and caspases have been targeted by a variety of
      imaging agents and modalities such as nuclear scintigraphy, PET, MRI, and
      fluorescent and bioluminescent imaging. Translationally, methods utilizing
      radiolabeled annexin V have proven promising in several clinical trials of
      ischemia-reperfusion injury and cardiac allograft rejection. New approaches using
      novel molecular imaging agents show great potential for the ability to image
      apoptosis in the research and clinical setting. Ultimately the ability to detect
      apoptosis noninvasively would help to identify patients for emerging anti
      apoptotic therapies and guide clinical management with the aim of maximal
      myocardial preservation.

PMID- 18074229
TI  - Effect of high beta-glucan barley on serum cholesterol concentrations and
      visceral fat area in Japanese men--a randomized, double-blinded, placebo
      controlled trial.
AB  - This study investigated whether the consumption of a diet in which high-beta
      glucan barley replaced rice would reduce the visceral fat area as well as the
      serum low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) in
      hypercholesterolemic Japanese men. A randomized, double-blinded, placebo
      controlled intervention study was conducted in 44 hypercholesterolemic Japanese
      men with a body mass index (BMI) >22 kg/m2. The subjects were randomly assigned
      to groups consuming either rice (placebo group) or a mixture of rice and pearl
      barley with a high beta-glucan content (test group, 7.0 g beta-glucan per day)
      for 12 weeks. Blood samples were taken, and CT scan obtained before the trial and
      every four weeks during the trial. The pearl barley intake significantly reduced
      serum concentrations of LDL-C (P = 0.041) and TC (P = 0.037) during the trial.
      Significant differences between the test and placebo groups were found for the
      visceral fat (P = 0.039), BMI (P = 0.015), and waist circumference (P = 0.011) at
      the end point. The consumption of pearl barley with a high beta-glucan content
      reduces not only LDL-C but also visceral fat area.

PMID- 18074230
TI  - Racial and ethnic disparities in the use of mental health services.
AB  - The authors used data from the 1998-1999 Community Tracking Study (CTS) household
      survey to examine variations in predictors of use of mental health services among
      different racial and ethnic groups (white, African American, Hispanic, and
      other). African Americans and Hispanics were less likely to have visited a mental
      health professional (MHP) in the prior year than were whites. Independent of
      health insurance and health status, low- to middle-income African Americans may
      be at particular risk for inadequate use of an MHP compared to higher-income
      African Americans. Similarly, upper-income Hispanics were more likely to have
      visited an MHP than Hispanics in the lowest income range. Adults aged 50 and
      older were less likely to visit an MHP than individuals aged 18-49. Depressed men
      were more likely to visit an MHP than depressed women. Efforts to reduce
      disparities should focus on lower-income racial and ethnic minorities.

PMID- 18074231
TI  - Decolorization of anthraquinone dye intermediate and its accelerating effect on
      reduction of azo acid dyes by Sphingomonas xenophaga in anaerobic-aerobic
      process.
AB  - Decolorization of 1-aminoanthraquinone-2-sulfonic acid (ASA-2) and its
      accelerating effect on the reduction of azo acid dyes by Sphingomonas xenophaga
      QYY were investigated. The study showed that ASA-2 could be efficiently
      decolorized by strain QYY under aerobic conditions according to the analysis of
      total organic carbon removal and UV-VIS spectra changes. Moreover, strain QYY was
      able to reduce azo acid dyes under anaerobic conditions. The effects of various
      operating conditions such as carbon sources, temperature, and pH on the reduction
      rate were studied. It was demonstrated that ASA-2 used as a redox mediator could
      accelerate the reduction process. Consequently the reduction of azo acid dyes
      mediated by ASA-2 and the decolorization of ASA-2 with strain QYY could be
      achieved in an anaerobic-aerobic process.

PMID- 18074232
TI  - Risk of thyroid cancer among Iranian immigrants in Sweden.
AB  - OBJECTIVES: Studies of immigrants are of value to elucidate the role of
      environmental factors in cancer causation, but large cohorts are needed in order
      to study rare cancers. We conducted a register-based study of a cohort of 59,274
      (32,236 men and 27,038 women) Swedish residents born in Iran, with follow-up
      between 1969 and 2004. We identified 50 incident cases of thyroid cancer during
      more than 800 thousands person-years of observation. METHODS: Rate ratios (RR)
      were calculated based on Poisson models estimated by the maximum likelihood
      method, using Swedish born residents with both parents born in Sweden as
      reference population. 95% confidence interval was estimated on the assumption
      that the observed numbers of cancers follow a Poisson distribution. RESULTS: The
      adjusted RR of thyroid cancer among Iranian immigrants was 2.6 (95% CI 2.0-3.5),
      without appreciable sex differences. In both sexes, the excess risk was highest
      among people who were younger than 30 years at immigration. Among women, the
      largest excess risk (adjusted RR = 4.6, 95% CI 2.9-7.4) was observed during the
      first 5 years from immigration, while for men, during the second decade from
      immigration. The rate ratio was higher among subjects who immigrated before 1990
      (adjusted RR = 2.7, 95% CI 2.0-3.8) than among those immigrated thereafter,
      particularly among men. CONCLUSION: The observed excess risk among Iranian
      immigrants compared to Swedish-born residents is compatible with differential
      burden of environmental risk factors, the most likely of which are iodine
      deficiency and high natural levels of ionizing radiation.

PMID- 18074233
TI  - Copper and Zinc in a paddy field and their potential ecological impacts affected
      by wastewater from a lead/zinc mine, P. R. China.
AB  - As well known, at normal levels, copper and zinc are essential micronutrients for
      plants, animals, and humans. However, excessive Cu and Zn are toxic and disturb a
      wide range of biochemical and physiological processes. Using Atomic Absorption
      Spectrophotometer (AAS; Perkin-Elmer 3030, USA), soil and rice plant (Oryza
      sativa L.) samples collected from a paddy field in Lechang lead-zinc mine area,
      Guangdong Province, China were analyzed and their potential ecological impacts to
      local human and livestock were evaluated. The results showed that the paddy soils
      were contaminated with Cu and Zn. Both metals in soils had low bio-available
      fractions for paddy plants, animal and human by three chemically analytical
      techniques. Generally, were concentrations of copper and zinc root >> straw >
      stalk > grain with hull > grain without hull (i.e. unpolished rice) and in the
      normal ranges indicating no ecological risk for local livestock and residents.
      All positive correlation coefficients, however, between heavy metals in rice
      plant and total, exchangeable (step 1 in Tessier's method established in 1979)
      and DTPA-extractable fractions in soils were found in this study indicating that
      elevated heavy metal in soils would increase long-term exposition and possible
      consequence of ecological hazard through food chains.

PMID- 18074234
TI  - Determination of some heavy metal levels and oxidative status in Carassius
      carassius L., 1758 from Eber Lake.
AB  - In this study, the levels of some heavy metals (Al, Cd, Co, Cr, Cu, Fe, Li, Mn,
      Ni, Pb and Zn) in muscle, gill, and liver of Carassius carassius and in the water
      samples from Eber Lake (Afyonkarahisar, Turkey) have been investigated.
      Additionally, one of the lipid peroxidation markers, malondialdehide (MDA) and
      glutathion (GSH) levels were investigated. All the metal analysis was performed
      by using ICP-AES. According to results obtained, it was observed that heavy
      metals were accummulated in liver in the highest degree and lowest one in the
      muscle tissues. MDA and GSH levels varied in the seasons but their winter levels
      were found to be statistically meaningful when compared with other seasons. The
      obtained data of metals from the study were compared with the acceptable levels
      of Turkish governmental regulation and they were found not to be harmful for
      human health. On the other hand, it was suggested that oxidative stress markers
      should be checked regularly in order to get important data for continuous life of
      aquatic organisms.

PMID- 18074235
TI  - Assessment of the potential hazards of nitrate contamination in surface and
      groundwater in a heavily fertilized and intensively cultivated district of India.
AB  - We made an inventory of nitrate (NO3-N) enrichment in surface and groundwater
      systems in the Hooghly district of India owing to intensive farming with high
      fertilizer doses as a function of quantity of fertilizers use, soil
      characteristics, types of crop grown, depth of groundwater sampling and also N
      load in soil profiles. Water samples were collected from different sources at 412
      odd sites spread over in 17 blocks of the district along with representative soil
      profiles. On average, the study area had high clay and NO3-N in soil profiles
      with an increasing and decreasing trends along depth, respectively. The NO3-N
      content both in surface and groundwater varied from 0.01 microg mL(-1) to 4.56
      microg mL(-1), being well below the threshold limit of 10 microg mL(-1) fixed by
      WHO for drinking purpose. The content decreased with increasing depth of wells (r
      = -0.39**) and clay content of soil profiles (r = -0.31**). It, however,
      increased with increasing rate of fertilizer application (r = 0.72**), NO3-N load
      in soil profiles (r = 0.85**) and was higher in areas where shallow--rather than
      deep-rooted crops are grown. Results indicated even under fairly high quantity of
      fertilizer use, groundwater of the study area is safe for drinking purpose.

PMID- 18074236
TI  - Biomonitoring study of heavy metals in biota and sediments in the South Eastern
      coast of Mediterranean sea, Egypt.
AB  - Concentrations of Cd, Cu, Co, Zn, Mn and Fe were determined in biota and sediment
      samples collected from the Eastern Harbour and El-Mex Bay in the Mediterranean
      Sea, Egypt. The levels of Cu, Co, Zn, Mn and Fe in the macroalgae, Ulva lactuca,
      Enteromorpha compressa (green algae) and Jania rubens (red algae), recorded high
      concentrations except for Cd. Moreover, Fe was the most predominant metal in the
      seaweed. The two species of bivalves, Donax trunculus and Paphia textile, showed
      different amounts of metals in their tissue. The abundance of heavy metal
      concentrations in the mussel samples was found in the order Fe> Zn> Mn> Cu> Co>
      Cd and Fe> Zn> Mn> Cu> Cd> Co, respectively for the two species. The metals
      concentrations were generally higher compared with the previous studies in
      mussels from the same area. The levels of metals accumulated in the investigated
      fish samples, Saurida undosquamis, Siganus rivulatus, Lithognathus mormyrus and
      Sphyraena sphyraena, were higher than those of Marmara Sea (Turkey), for Co and
      Cd and lower for Cu, Zn, Mn and Fe. El-Mex Bay having the highest metals
      concentration in sediments as their order of abundance were Fe> Zn> Mn> Cu> Cd>
      Co. Nevertheless, a high variability in the metal levels occurs among the studied
      algae and biota and also between the investigated Harbour. A significant
      correlations (p < 0.05) were found for each of Zn and Fe in P. textile and of Co
      in D. trunculus relative to their concentrations in surficial sediments.

PMID- 18074237
TI  - Distribution, sources, and potential risk of polycyclic aromatic hydrocarbons
      (PAHs) in drinking water resources from Henan Province in middle of China.
AB  - Distribution and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in
      drinking water resources have been carried out for the first time in Henan
      Province, China. Water samples collected from four river systems and their
      tributaries, as well as groundwater resources, were analyzed according to EPA
      method 525.2. Total of 68 water samples were collected in 18 cities in Henan
      province in May, August and November, 2001. Concentrations of sum of 16 priority
      PAHs in water samples ranged from 15 to 844 ng/L with a mean value of 178 +/- 210
      ng/L (n = 68). The spatial and temporal distribution of PAHs showed that the
      Huanghe and the Huaihe river systems had relatively higher concentrations of
      total PAHs. Higher concentrations of total PAHs were observed in August and
      November than in May, with respective mean values of 262, 232 and 33.6 ng/L.
      Ratios of Ant/(Ant + Phe) and Flur/(Flur + Pyr) were calculated to evaluate the
      possible sources of PAH contamination, which indicated that the coal combustion
      sources were the main contributors to PAHs in most drinking water resources. Some
      petrogenic (or pyrolytic) sources of PAHs were also found. The toxic equivalency
      factors (TEFs) were used to calculate benzo[a]pyrene equivalents (BaPE) for water
      samples. The average value of BaPE was 0.6 ng/L. The values in most stations were
      much lower than the guideline values in drinking water of Chinese Environmental
      Protection Agency (CEPA, 2.8 ng/L) and the US Environmental Protection Agency (US
      EPA, 200 ng/L). Overall, the drinking water resources in Henan province showed
      some carcinogenic potential.

PMID- 18074238
TI  - Nonpoint source pollution loading from an undistributed tropic forest area.
AB  - Water quality and unit nonpoint sources (NPS) pollution load from a forest area
      were studied in a mountainous watershed in Taiwan. The flow rates were measured
      with rectangular weirs and samples taken for water quality analysis in both non
      rainy and rainy days for 2 years. The subroutine of the Hydrological Simulation
      Program--FORTRAN was used to simulate runoff for additional 3 years. Total annual
      loads of various water quality parameters were then estimated by a regression
      model. Most of the parameter concentrations are higher during the rainy days;
      their values are typically higher as compared to data from other undisturbed
      forest areas. Nevertheless, the concentration ratio of dissolved inorganic
      nitrogen to TN or PO4(3-) -P to TP shows TN or TP no correlations with the flow
      rates, whereas the concentrations of SS and TP are positively correlated with the
      flow rate. The fluctuation of annual load from this watershed is significant. For
      example, six major events of the entire year, for which the total duration is
      merely 6.4 days, contribute 42% of the annual precipitation and at least 40% of
      the annual NPS loads. The management for controlling the NPS pollution from this
      forest watershed is discussed.

PMID- 18074239
TI  - Genetic evaluation of von Hippel-Lindau disease for early diagnosis and improved
      prognosis.
AB  - von Hippel-Lindau disease (VHL) is a rare autosomal-dominant disorder in which
      affected individuals develop tumors in a number of locations. It occurs at a
      frequency of one per 36,000 population. Metastatic renal cell carcinoma (RCC)
      remains the leading cause of mortality in patients with clear cell RCC arising
      from mutations in the VHL tumor suppressor. RCC is the presenting feature in only
      10% of VHL patients. VHL patients can present with a number of other renal
      lesions, such as hemangiomas and benign adenomas, in addition to simple cysts and
      RCC. We have investigated VHL gene mutations in familial RCC. The study cohort
      consisted of four patients with synchronous VHL and RCC and 31 kindreds. Analysis
      of the chromosomes was performed by the Moorehead method. Although none of the
      kindreds investigated had clinical evidence of VHL disease, 22 were found to have
      a VHL gene mutation consisting of deletions on the short arm of chromosomes 3,
      17, and 19. Detailed clinical examination of the 22 kindreds with a VHL mutation
      revealed cerebellar hemangioblastoma (three kindreds), meningioma (two) and renal
      cell carcinoma (five). No VHL gene mutation was detected in nine kindreds. The
      prevalence of VHL gene mutations was 70.9% in the familial RCC kindreds. As a
      result of this study, the kindreds of patients with synchronous VHL and RCC have
      undergone molecular genetic testing and should be investigated for associated
      disorders.

PMID- 18074240
TI  - Strain and strain rate deformation parameters: from tissue Doppler to 2D speckle
      tracking.
AB  - Strain and strain rate deformation parameters based on Color Doppler Myocardial
      Imaging, and more recently on two-dimensional (2D) gray scale images, have
      evolved as important methods for the quantification of myocardial function.
      Although these parameters are already applicable in the research field, their
      acquisition and analysis involve a number of technical challenges and
      complexities. Accurate knowledge of the basic principles of those techniques, as
      presented in this article, will further enhance their applicability to clinical
      practice.

PMID- 18074241
TI  - Angiographic core laboratory reproducibility analyses: implications for planning
      clinical trials using coronary angiography and left ventriculography end-points.
AB  - OBJECTIVES: To assess reproducibility of core laboratory performance and impact
      on sample size calculations. BACKGROUND: Little information exists about overall
      reproducibility of core laboratories in contradistinction to performance of
      individual technicians. Also, qualitative parameters are being adjudicated
      increasingly as either primary or secondary end-points. The comparative impact of
      using diverse indexes on sample sizes has not been previously reported. METHODS:
      We compared initial and repeat assessments of five quantitative parameters [e.g.,
      minimum lumen diameter (MLD), ejection fraction (EF), etc.] and six qualitative
      parameters [e.g., TIMI myocardial perfusion grade (TMPG) or thrombus grade (TTG),
      etc.], as performed by differing technicians and separated by a year or more.
      Sample sizes were calculated from these results. TMPG and TTG were also
      adjudicated by a second core laboratory. RESULTS: MLD and EF were the most
      reproducible, yielding the smallest sample size calculations, whereas percent
      diameter stenosis and centerline wall motion require substantially larger trials.
      Of the qualitative parameters, all except TIMI flow grade gave reproducibility
      characteristics yielding sample sizes of many 100's of patients. Reproducibility
      of TMPG and TTG was only moderately good both within and between core
      laboratories, underscoring an intrinsic difficulty in assessing these.
      CONCLUSIONS: Core laboratories can be shown to provide reproducibility
      performance that is comparable to performance commonly ascribed to individual
      technicians. The differences in reproducibility yield huge differences in sample
      size when comparing quantitative and qualitative parameters. TMPG and TTG are
      intrinsically difficult to assess and conclusions based on these parameters
      should arise only from very large trials.

PMID- 18074242
TI  - Health-related quality of life of day-case surgery patients: a pre/posttest
      survey using the EuroQoL-5D.
AB  - AIM: This paper describes and compares the perceived health-related quality of
      life (HRQoL) of day-case surgery patients before and after their procedures and
      examines some associated patient-related factors. METHOD: A pre/posttest survey
      design was employed to collect data from Finnish adult day-case surgery patients
      using participant-completed EuroQoL 5-Dimensional Classification Component Scores
      (EQ-5D) questionnaires given 2 weeks presurgery (n = 131) and 2 weeks postsurgery
      (n = 131) in 2004. RESULTS: No noticeable change after minor surgery was found
      using the EQ-5D. Using the EQ-5D index, patients perceived their HRQoL as high
      before and after surgery. Almost one fifth (17%) reported no pain or discomfort
      before the procedure compared with 40% after it. As measured by the EuroQol
      visual analogue scale (EQ(VAS)), those patients who reported chronic illness
      before the operation had a lower perception of their HRQoL compared with those
      who did not. It was also found that self-care and usual activities were more
      disturbed after surgery. CONCLUSIONS: Although there were increases and decreases
      within items of the EQ-5D, overall, there was no improvement on EQ-5D scores.
      More research is needed to explore the sensitivity and responsiveness of the EQ
      5D measure in day-case surgery patients.

PMID- 18074243
TI  - Application of a sensemaking approach to ethics training in the physical sciences
      and engineering.
AB  - Integrity is a critical determinant of the effectiveness of research
      organizations in terms of producing high quality research and educating the new
      generation of scientists. A number of responsible conduct of research (RCR)
      training programs have been developed to address this growing organizational
      concern. However, in spite of a significant body of research in ethics training,
      it is still unknown which approach has the highest potential to enhance
      researchers' integrity. One of the approaches showing some promise in improving
      researchers' integrity has focused on the development of ethical decision-making
      skills. The current effort proposes a novel curriculum that focuses on broad
      metacognitive reasoning strategies researchers use when making sense of day-to
      day social and professional practices that have ethical implications for the
      physical sciences and engineering. This sensemaking training has been implemented
      in a professional sample of scientists conducting research in electrical
      engineering, atmospheric and computer sciences at a large multi-cultural, multi
      disciplinary, and multi-university research center. A pre-post design was used to
      assess training effectiveness using scenario-based ethical decision-making
      measures. The training resulted in enhanced ethical decision-making of
      researchers in relation to four ethical conduct areas, namely data management,
      study conduct, professional practices, and business practices. In addition,
      sensemaking training led to researchers' preference for decisions involving the
      application of the broad metacognitive reasoning strategies. Individual trainee
      and training characteristics were used to explain the study findings. Broad
      implications of the findings for ethics training development, implementation, and
      evaluation in the sciences are discussed.

PMID- 18074244
TI  - Cloning and characterization of a cytosolic glutamine synthetase from Camellia
      sinensis (L.) O. Kuntze that is upregulated by ABA, SA, and H2O2.
AB  - A cDNA encoding glutamine synthetase, one of the enzymes of the GS/GOGAT pathway,
      was cloned from Camellia sinensis (CsGS). The isolated cDNA consists of 1,071
      nucleotides encoding a polypeptide of 356 amino acids with an estimated
      isoelectric point of 6.13. The recombinant protein purified from Escherichia coli
      using Ni-NTA affinity chromatography showed molecular mass of 39.2 kDa. The
      purified protein was confirmed by blotting with anti-His antibodies. Catalytic
      parameters of the protein were determined using glutamate and ATP as substrates.
      The observed Km was 9 mM and Vmax was 93 U/mg protein with glutamate as
      substrate, while with ATP Km and Vmax values were 6 mM and 70 U/mg protein,
      respectively. Purified enzyme showed pH optima at 8. Cations were found to be
      showing enhancing effect on the activity of GS enzyme and Mg2+ ion exhibited
      maximum enhancing effect among the various ions used in this study. This enzyme
      activity increased by 25% in presence of DTT and decreased by 18% when incubated
      with PMSF. Transcript analysis in tea bud, youngest leaf, showed that CsGS gene
      expression is stimulated in response to abscisic acid (ABA), salicylic acid (SA),
      and hydrogen peroxide (H2O2), while gibberellic acid (GA3) has no influence on
      its expression levels.

PMID- 18074245
TI  - Understanding and management of male breast cancer: a critical review.
AB  - Breast cancer is a rare disease in men representing nearly 1% of the total breast
      cancer cases worldwide. While treatments developed for women with breast cancer
      are often applied to treat men with breast cancer, however, lack of awareness of
      this disease leads to its detection at a later stage in men. This review
      discusses male breast cancer and draws comparisons with female breast cancer and
      discusses current treatments available to treat this disease. It is believed that
      this review shall provide concise and relevant information increasing the
      awareness of issues revolving around male breast cancer (MBC).

PMID- 18074248
TI  - Exciting advances in family caregiver research.

PMID- 18074246
TI  - Mesenchymal stem cell preparations--comparing apples and oranges.
AB  - Mesenchymal stem cells (MSC) represent a type of adult stem cells that can easily
      be isolated from various tissues and expanded in vitro. Past reports on their
      pluripotency and possible clinical applications have raised hopes and interest in
      MSC. Multiple designations have been given to different MSC preparations. So far
      MSC are poorly defined by a combination of physical, phenotypical and functional
      properties. As MSC could be derived from different tissues as starting material,
      by diverse isolation protocols, cultured and expanded in different media and
      conditions, the MSC preparations from different laboratories are highly
      heterogeneous. All of these variables might have implications (1) on the
      selection of cell types and the composition of heterogeneous subpopulations; (2)
      they can selectively favor expansion of different cell populations with totally
      different potentials; or (3) they might alter the long term fate of adult stem
      cells upon in vitro culture. The recent controversy on the multilineage
      differentiation potentials of some specific MSC preparations might be attributed
      to this lack of common standards. More precise molecular and cellular markers to
      define subsets of MSC and to standardize the protocols for expansion of MSC are
      urgently needed.

PMID- 18074249
TI  - Modification of dysfunctional thoughts about caregiving in dementia family
      caregivers: description and outcomes of an intervention programme.
AB  - Among the diverse group of interventions developed to help dementia family
      caregivers cognitive-behavioural approaches show especially promising results.
      OBJECTIVES: This study describes a cognitive-behavioural group intervention aimed
      principally at the modification of dysfunctional thoughts associated with
      caregiving (MDTC). The efficacy of the MDTC intervention in reducing caregivers'
      depressive symptomatology, together with the frequency and appraisal of problem
      behaviours, is compared to that of a waiting-list control group (WL).
      Furthermore, the potential mediating role of the dysfunctional thoughts in the
      relationship between this intervention and caregivers' depressive symptomatology
      is analyzed. Of the 74 dementia caregivers who were randomized to one of two
      conditions (MDTC and WL), 39 completed the post-intervention assessment.
      Statistical analyses were performed on an intention-to-treat basis, using last
      observation carried forward. The results reveal that the MDTC intervention is
      successful in reducing caregivers' level of depressive symptomatology and
      dysfunctional thoughts about caregiving, as well as in modifying their appraisal
      of their relative's problem behaviours. Furthermore, a mediating role for
      dysfunctional thoughts was found in the relationship between the MDTC
      intervention and levels of depressive symptomatology. The relevance of addressing
      dysfunctional thoughts and cognitive distortions in group interventions with
      caregivers is highlighted.

PMID- 18074250
TI  - The influence of stressors, appraisal and personal conditions on the burden of
      spousal caregivers of persons with dementia.
AB  - OBJECTIVES: The aim of this study was to explore the main and mediating
      influences of stressors, a caregiver's appraisal, coping, personal conditions and
      social resources on the burden of dementia caregivers. METHOD: The study sample
      consisted of 95 spousal caregivers of non-institutionalized persons with
      dementia. A path-analytic approach was used to test the conceptual model.
      RESULTS: The most important factors that were related to burden were the social
      and behavioural problems of the person with dementia; perceiving the caregiver
      role as a threat; perceived instrumental support; and the caregiver's functional
      health status and self-efficacy. The results showed no support for the mediating
      role of appraisal and coping on the relationship between the demands of the
      caregiving situation and burden. CONCLUSION: Although we found insufficient
      support for the empirical tenability of the hypothesised model, this study
      revealed some new findings of practical interest. The relationships found suggest
      that it might be possible to reduce the caregiving burden by improving the social
      functioning of the person with dementia, the caregiver's perceptions and the
      caregiver's capacity to function in daily life.

PMID- 18074251
TI  - The attenuating effect of personal mastery on the relations between stress and
      Alzheimer caregiver health: a five-year longitudinal analysis.
AB  - The objectives of this study were to evaluate the impact of personal mastery and
      caregiving stress on caregiver depressive symptoms and health over time and to
      examine the moderating effect of mastery on the relations between stress and
      these outcomes. A total of 130 spousal Alzheimer caregivers completed yearly
      assessments of personal mastery, role overload, health symptoms and depressive
      symptoms. Random regression was used to evaluate the relations between time
      varying values for stress and mastery in predicting depressive and health
      symptoms. It was found that variation in depressive symptoms over time was
      significantly related to role overload (p<0.05) and personal mastery (p<0.001). A
      significant overload-by-mastery interaction was found for predicting depressive
      symptoms (p=0.002) and caregiver health (p=0.008), whereby mastery attenuated the
      effect of stress on these outcomes. We conclude that personal mastery appears to
      reduce the effects of stress on depression and health outcomes over time.

PMID- 18074252
TI  - Effects of psychotherapy and other behavioral interventions on clinically
      depressed older adults: a meta-analysis.
AB  - OBJECTIVES: The goal of the present study was to assess the effects of
      psychotherapy and other behavioral interventions on depressive symptoms in
      clinically depressed older patients. METHODS: We used meta-analysis to examine
      the effects of 57 controlled intervention studies. RESULTS: On average, self
      rated depression improved by d=0.84 standard deviation units and clinician-rated
      depression improved by d=0.93. Effect sizes were large for cognitive and
      behavioral therapy (CBT) and reminiscence; and medium for psychodynamic therapy,
      psychoeducation, physical exercise and supportive interventions. Age differences
      in treatment effects were not observed. Weaker effects were found in studies that
      used an active control group and in studies of physically ill or cognitively
      impaired patients. Studies of samples comprised exclusively of patients suffering
      from major depression (versus other mood disorders) also yielded weaker
      intervention effects. On average, 18.9% of participants did not complete the
      intervention, with higher dropout rates reported in group (versus individual)
      interventions and in longer interventions. CONCLUSIONS: We conclude that
      cognitive-behavioral therapy and reminiscence are particularly well-established
      and acceptable forms of depression treatment. Interventions with 7-12 sessions
      may optimize effectiveness while minimizing dropout rates. For physically and
      cognitively impaired patients, modifications in treatment format and/or content
      might be useful, such as combining psychotherapy with social work interventions
      and pharmacotherapy.

PMID- 18074253
TI  - Does sense of coherence affect the relationship between self-rated health and
      health status in a sample of community-dwelling frail elderly people?
AB  - BACKGROUND: The objective of this study was to examine the association between
      self-rated health (SRH) and physical, functional, social and mental health
      measures in community dwelling elderly people needing nursing care. Of special
      interest was how coping resources (SOC) influenced this relationship. Self-rated
      health is a good predictor of future health status as measured by mortality and
      morbidity, decline of functional abilities, use of healthcare, and nursing home
      placement. The high mean age and the relatively high level of care-dependency in
      this sample, make this investigation important. METHODS: A hierarchical
      regression analysis was applied in a cross sectional sample of 242 elderly (mean
      age 84.6 years). RESULTS: Subjective health complaints (SHC) in both sexes, and
      psychological distress (only in men), was associated directly with SRH. Coping
      resources associated with SRH directly, and indirectly through subjective
      perceived health (SHC and GHQ) but only in men. The influence of registered
      illness was mediated through the effects of subjectively perceived health in both
      women and men. Sex differences moderated the effects of SOC on SRH. CONCLUSION:
      Subjectively perceived health was more important in the perception of SRH than
      objective health measures. Men, in contrast to women, tend to convert physical
      illness into emotional distress.

PMID- 18074254
TI  - Self-report measures of anxiety: are they suitable for older adults?
AB  - OBJECTIVES: To assess the performance of four self-report measures of anxiety in
      an older adult population. METHOD: Forty older adults with current or previous
      anxiety symptoms completed four self-report measures of anxiety (Beck Anxiety
      Inventory, State Trait Anxiety Inventory, Hospital Anxiety and Depression Scale
      and Visual Analogue Scale) and received an independent diagnostic assessment and
      rating of anxiety severity. After a minimum of four months, participants were re
      assessed on all measures. RESULTS: The self-report measures most suited for
      anxiety screening and assessing severity when compared to the independent
      assessment were the Beck Anxiety Inventory (BAI), the anxiety scale from the
      Hospital Anxiety and Depression Scale (HADS-A) and State Trait Anxiety Inventory
      Trait form (STAI-T). However, participants made an unacceptably high number of
      errors using the STAI-T, making the BAI and HADS-A the most suitable measures for
      older adults. The Visual Analogue Scale (VAS) performed poorly in both screening
      and measuring severity. All self-report measures were poor at detecting change as
      evaluated by the independent assessment. CONCLUSION: There was no single measure
      that performed adequately in screening, measuring severity and monitoring
      changes, suggesting that measures may need to be adapted if they are to be used
      in an older adult population. The lack of appropriately designed self-report
      measures with adequate normative data for older people presents a barrier to
      future research.

PMID- 18074255
TI  - Reliability generalization of responses by care providers to the Zarit Burden
      Interview.
AB  - The Zarit Burden Interview (ZBI) is believed to be the most commonly used measure
      of caregiver burden. Originally developed more than 20 years ago for use with
      informal caregivers of community dwelling persons with Alzheimer disease, it has
      subsequently been administered to a diverse range of patient populations, formal
      or paid caregivers, and translated into numerous languages. Given that the ZBI is
      now used more broadly than it was initially intended and first validated, the
      current study applies the reliability generalization meta-analytic procedure to
      examine the psychometric properties of responses to the ZBI across populations.
      Multiple regression with categorical variables was performed to identify factors
      associated with error variance in ZBI reliability estimates (N=138 data points).
      Number of items, residence of the care recipient (community) and the Hebrew
      version each contributed significantly to prediction of internal consistency.
      These differences, however, were found to be relatively small and within accepted
      parameters. Generally, responses to the ZBI appear reliable across populations of
      caregivers and patients. Only versions of the ZBI with more or less than 22-items
      (nonstandard formats) reflect both statistical and meaningful differences in
      reliability. Where feasible, it is recommended that the 22-item version of the
      ZBI be used in future research and clinical practice.

PMID- 18074256
TI  - Mapping the maze of terms and definitions in dementia-related wandering.
AB  - PURPOSE: An operational definition of dementia-related wandering is proposed to
      aid in clinical recognition, to promote research precision and validity, and to
      provide a pathway toward standardization of language in wandering science. DESIGN
      AND METHODS: (1) One-hundred-and-eighty-three journal articles from multiple
      databases (Medline, OVID, CSA Journals, OCLC First Search, Google Scholar,
      PubMed, EBSCO) were reviewed to extract alternative terms and definitions for
      wandering or wandering-related behaviours; (2) terms and definitions were ordered
      alphabetically into a glossary; (3) a consensus approach was used to group
      glossary terms with related meanings into possible domains of wandering; (4) four
      domains (locomotion, drive, space and time) were found sufficient to encompass
      all wandering definitions; (5) wandering terms were placed into a conceptual map
      bounded by the four domain concepts and (6) a new provisional definition of
      wandering was formulated. RESULTS: An empirically-based, operational definition
      improves clinical and research approaches to wandering and explicates historical
      inattention to certain beneficial aspects of the behaviour. IMPLICATIONS:
      Adoption of the proposed operational definition of wandering behaviour provides a
      platform upon which dementia care may be improved and standardized language may
      evolve in wandering science.

PMID- 18074257
TI  - Does social participation by the elderly reduce mortality and cognitive
      impairment?
AB  - PURPOSE: This longitudinal study examines the effect of social participation on
      mortality and cognitive impairment for the elderly in Taiwan. METHODS: Data were
      from an elderly population panel in Taiwan 'The Survey of Health and Living
      Status of the Elderly' 1993-1999. Social participation was defined as paid/unpaid
      job and participating in volunteer and social groups. Logistic regression
      analysis was used for predicting the influence of social participation to 6-year
      mortality and cognitive function impairment, by controlling of socioeconomic
      status and health-related variables. RESULTS: The elderly with continuous paid
      work were more likely to participate in social groups. Having paid or unpaid work
      at the baseline year could lower the risk of mortality six years later,
      especially for men. Having unpaid work was associated with a higher risk of
      impaired cognitive function compared to that of non-workers. Participating in a
      religious group reduced the risk of mortality for women and participating in
      political groups reduced the risk of impaired cognitive function for men.
      DISCUSSION: Participating in some types of social activities may reduce mortality
      or cognitive function impairment in the elderly. However, different activities,
      gender roles and uneven opportunities for work and social group participation may
      affect the risk of these endpoints.

PMID- 18074259
TI  - A cognitive intervention to enhance institutionalized older adults' social
      support networks and decrease loneliness.
AB  - Nearly all older adults experience social losses, which can disrupt their social
      support networks and impair their quality of life. Events such as retirement, an
      inability to drive, death of a spouse and/or close life-long friends, or moving
      to an elder care facility may negatively affect the quality of older adults'
      social support networks. Low levels of perceived social support are associated
      with increased depression, impaired immune functioning and reduced life
      expectancy. Moreover, social interactions can be cognitively stimulating and may
      help older adults preserve their cognitive abilities. In the present study,
      institutionalized older adults were exposed to either a cognitive enhancement
      programme designed to enhance social networks or a control group. Measures of
      perceived social support and loneliness were administered before and after a 3
      month, group-based intervention. There was a significant interaction between
      group and time. Those who did not participate in the intervention experienced a
      decrease in perceived social support and an increase in perceived loneliness.
      Participants in the intervention group stayed the same on the above measures.
      Helping older adults increase or maintain the quality of their social networks
      may lead to enhanced cognitive functioning, decreased depression and improved
      quality of life. Recommendations to help assisted living facilities, nursing
      homes, retirement communities and senior centres develop social and cognitive
      interventions are provided.

PMID- 18074258
TI  - The link between depressive symptoms, negative cognitive bias and memory
      complaints in older adults.
AB  - OBJECTIVES: We sought to examine the relationship between depressive symptoms and
      subjective memory problems. We hypothesized that the relationship between
      depressive symptoms and poor subjective memory functioning is mediated by
      negative cognitive bias that is associated with hopelessness, a wish to die and
      low self-esteem. METHODS: Complete data were available for 299 older adults with
      and without significant depressive symptoms who were screened in primary care
      offices and invited to participate, completed a baseline in-home assessment.
      Subjective memory functioning and psychological status was assessed with commonly
      used, validated standard questionnaires. RESULTS: In regression models that
      included terms for age, gender and cognitive measures, depressive symptoms were
      significantly inversely associated with the global self-assessment of memory
      (beta=-0.019; p=0.006). When components of negative cognitive bias were included
      in the model (hopelessness, low self-esteem, a wish to die), the relationship of
      depressive symptoms with subjective memory problems was attenuated, consistent
      with mediation. CONCLUSIONS: Our results suggest that assessment and successful
      interventions for memory complaints in non-demented older adults need to account
      for negative cognitive bias as well as depressive symptoms. Longitudinal research
      is needed to confirm our findings before a mediator relationship can be presumed.

PMID- 18074260
TI  - Development of a nursing home vision-targeted health-related quality of life
      questionnaire for older adults.
AB  - PURPOSE: To develop a questionnaire assessing vision-targeted health-related
      quality of life in older adults residing in nursing homes. METHODS: Using content
      previously identified through structured interviews with nursing home residents,
      the 57-item Nursing Home Vision-Targeted Health-Related Quality of Life
      questionnaire (NHVQoL) was drafted with nine subscales - general vision, reading,
      ocular symptoms, mobility, psychological distress, activities of daily living,
      activities/hobbies, adaptation/coping and social interaction. Construct validity
      and internal consistency and test-retest reliability of subscales were evaluated
      in a sample of adults >or=60 years old residing in nursing homes in Birmingham,
      Alabama, who had Mini Mental State Exam (MMSE) scores of >or=13. RESULTS:
      Participants (n=189) had a mean age of 82 years (SD=7.7), were 84% women and 16%
      men, 24% African-American and 76% Caucasian and had resided in a nursing home for
      two years on average. All NHVQoL subscales were correlated with subscales from
      other vision-targeted and generic health-related quality of life instruments
      (ADVS, 0.43 to 0.85; VF-14, 0.46 to 0.84; SF-36, 0.19 to 0.43). Lower scores were
      associated with increased depressive symptomatology by the Geriatric Depression
      Scale (-0.23 to -0.59), increased mobility problems (-0.17 to -0.54), worse
      distance and near acuity (-0.21 to -0.51) and worse contrast sensitivity (0.20 to
      0.50). All subscales had Cronbach alpha>0.95. Test-retest reliability (two-week
      period) for subscales ranged from 0.57 to 0.84. Subscale scores did not differ as
      a function of MMSE scores. CONCLUSIONS: The NHVQoL has subscales with good
      internal consistency reliability and validity. Test-retest reliability is
      comparable to other questionnaires designed for the nursing home population. This
      questionnaire may ultimately be useful in understanding the personal burden of
      visual impairment and eye disease on quality of life and mental health in older
      nursing home residents and for evaluating the impact of psychosocial and eye care
      interventions on health-related quality of life in this population.

PMID- 18074261
TI  - Self report on quality of life in dementia with modified COOP/WONCA charts.
AB  - This study investigates whether a modified version of the COOP/WONCA charts is
      suitable to assess quality of life (QOL) in persons with dementia in nursing
      homes. A group of 112 institutionalized persons with moderate to severe dementia
      were approached for an interview. Twenty-two were observed not to be
      communicative, leaving 90. Sixty-seven persons were able to answer four out of
      six questions adequately (interviewable). Inter-observer reliability (n=38) was
      excellent (weighted kappa 0.90 to 0.97). Test-retest reliability (n=34; one week
      interval) ranged from poor for Daily and Social Activities and for the QOL
      charts, to moderate for Feelings and Pain, and satisfactory for Physical
      Functioning (weighted kappa 0.23 to 0.67). Interviewability was associated with
      severity of the dementia and communication ability. Support for convergent
      validity was found in medium-sized Spearman correlations between the COOP/WONCA
      charts and related variables. Support for discriminant validity was found in the
      absence of association between the Ccharts and non-related variables. The
      modified COOP/WONCA charts can be used to assess QOL in 60% of people with
      dementia in nursing homes but further modification is needed. Severe cognitive
      impairment and communication disabilities proved limiting factors for the use of
      the instrument. Although the illustrations on the charts appeared not to be
      helpful, the written response options in addition to verbal presentation proved
      useful during the administration of the charts.

PMID- 18074262
TI  - Rural-urban differences in the effects on mental well-being of caring for people
      with stroke or dementia.
AB  - BACKGROUND: Rural and urban differences in the effects of care-giving are not
      well documented. This paper reports data on 122 carers for people with stroke or
      dementia living in rural and urban settings in Wales. METHOD: Carers completed a
      postal questionnaire, including the SF-12v2 Health Survey. Definitions of rural
      and urban were based on the Urban/Rural Indicator from the Office of National
      Statistics (ONS) All Fields Postcode Directory 2004. RESULTS: Carers' mean Mental
      Component Summary (MCS) score (adjusted for age and sex) was one standard
      deviation below the population mean (-12.03). Male carers living in urban areas
      reported better mental health than male carers in rural areas (p<0.05) and female
      carers in both settings (p<0.05). A full model and a parsimonious model were
      developed, using MCS scores as outcome variables. In the full model sitting
      service provision in rural and urban locations was linked to better carer mental
      health, while support from friends and family was linked to better mental health
      for urban carers only. CONCLUSION: Our findings indicate the existence of both
      gender and location differences in carer experiences.

PMID- 18074263
TI  - Activity participation and affect among nursing home residents: support for a
      behavioural model of depression.
AB  - One focus of interventions being developed for depression in nursing homes is
      increasing pleasant events. The conceptual foundation of such interventions
      requires establishing links among activity levels, depressive symptoms and
      positive affect. We observed activity and affect among 28 nursing home residents,
      five-days-a-week for four weeks, and concurrently collected self-reported affect
      and depression data. Inclusion of intra-individual analyses using random effects
      models demonstrated considerable individual variability in the relationship
      between positive affect and activity, although the results broadly supported the
      association. Participants differed with regard to what types of events were
      pleasurable and with regard to the relationships among pleasure, interest and
      activity. Depression levels were related to some of these individual differences.
      Activity was related primarily to interest rather than pleasure and higher
      interest was related to fewer depressive symptoms. Our findings emphasize the
      importance of individually tailoring pleasant events interventions and suggest
      that prescriptive group activities are unlikely to prove effective as means for
      improving positive affect.

PMID- 18074264
TI  - Awareness of memory functioning in early Alzheimer's disease: lessons from a
      comparison with healthy older people and young adults.
AB  - To compare awareness of memory in people with early Alzheimer's disease (AD) with
      older and younger control groups in order to clarify the contributions of disease
      and ageing. Twenty-one individuals with early AD, 32 older people (OP) and 32
      younger people (YP) estimated their performance before and following each of four
      tests of memory. Those with AD significantly overestimated performance prior to
      testing, confirming the presence of unawareness for prediction. Their estimates
      were adjusted for age in a similar way to those of OP, who predicted their
      performance accurately. Younger people significantly underestimated their
      performance. Following memory tests, YP and those with AD significantly adjusted
      their ratings towards greater accuracy but on average those with AD still
      overestimated. There were variations in post-test ratings from over to under
      prediction in all three groups. Heightened awareness post-performance may open
      possibilities of cognitive rehabilitation to consolidate momentary into more long
      term awareness, whilst the operation of possible psychosocial influences suggests
      that emotion oriented interventions to increase acceptance and decrease shame
      might be helpful.

PMID- 18074265
TI  - The history, chemistry and modes of action of carmine and related dyes.
AB  - Carmine has been used in biological staining to demonstrate selectively nuclei,
      chromosomes or mucins, depending on the formulation. Throughout its history in
      science, complaints and frustrations have been expressed about dye quality.
      Inconsistencies in dye quality or identity have prevented thorough understanding
      of staining mechanisms and have caused many stain solutions to behave
      unsatisfactorily. The aim of this review is to (1) detail causes of these
      problems, which are rooted in history, geography and production, (2) offer ways
      to minimize problems and (3) provide modern explanations for stain behavior.
      Carmine is a "semi-synthetic" dye, i.e., a complex of aluminum and the natural
      dye cochineal (carminic acid). Carmine shows considerable batch-to-batch
      variability. Geography, politics, history, agricultural practices and iconography
      all contribute to the variability of cochineal. In addition, widely divergent
      manufacturing methods are used to produce carmine. Also, confusion in terminology
      has led to mislabeling. Pressure from the food industry for a more satisfactory
      colorant for acidic foods led to the introduction of a new dye, aminocarminic
      acid, which could enter the biological market inadvertantly. Improved methods of
      analysis should help the certification process by the Biological Stain
      Commission. Further standardization could be achieved by replacing most of the
      methods of solubilizing carmine. The majority of these methods use heat, which is
      likely to damage the dye molecule. Fortunately, carmine is readily dissolved by
      raising the pH of the aqueous solvent above 12, and a new form of the dye, now
      available commercially, is soluble in water without the need for heat or pH
      adjustment. Chemical structures and physical properties of carminic acid,
      carmine, aminocarminic acid and kermesic acid are reviewed. A new configuration
      for carmine is proposed, as well as possible changes to carminic acid and carmine
      molecules as a result of decomposition caused by heating. Each of the major
      classes of carmine-based stains is described as are possible mechanisms of
      attachment to specific substrates. Glycogen binds carmine through hydrogen
      bonding, and it is here that carmine decomposed by heat could have the greatest
      detrimental impact. Nuclei and chromosomes are stained via coordination bonds,
      perhaps supplemented by hydrogen bonds. Finally, acidic mucins react ionically
      with carmine. Specificity in the latter case may be due to unique polymeric
      carmine molecules that form in the presence of aluminum chloride.

PMID- 18074266
TI  - Modern techniques for protein detection on polyacrylamide gels: problems arising
      from the use of dyes of undisclosed structures for scientific purposes.

PMID- 18074267
TI  - Combined histochemistry and autofluorescence for identifying lignin distribution
      in cell walls.
AB  - Histological staining methods commonly used for detecting cellulose and lignin in
      cell walls were combined with epifluorescence microscopy to visualize differences
      in lignification between and within cellular elements. We tested our approach on
      sections of one-year-old branches of Fraxinus ornus L., Myrtus communis L., Olea
      europaea L., Pistacia lentiscus L. and Rhamnus alaternus L., containing both
      normal and tension wood. Sections were subjected to various staining techniques,
      viz. safranin O, safranin O/fast green FCF, and alcoholic solutions of safranin
      O/astra blue, according to the commonly accepted protocols. Stained and unstained
      sections were compared using both light and epifluorescence microscopy. Safranin
      O with or without counterstaining hid the strong fluorescence of vessel walls,
      cell corners and middle lamellae allowing the secondary wall fibers to fluoresce
      more clearly. Epifluorescence microscopy applied to stained sections showed more
      cell wall details than autofluorescence of unstained sections or white light
      microscopy of counterstained sections. This simple approach proved reliable and
      valuable for detecting differences in lignification in thick sections without the
      need for costly equipment.

PMID- 18074268
TI  - Morphologic complexity of the pericellular matrix in the annulus of the human
      intervertebral disc.
AB  - The pericellular region of the extracellular matrix (ECM) contains collagens,
      proteoglycans and other noncollagenous matrix proteins. Although such specialized
      pericellular ECM has been well studied in articular cartilage, little is known
      about the pericellular matrix in the disc. In the study reported here,
      pericellular matrix was studied in annulus tissue from 52 subjects ranging in age
      from 17-74 years. In aging/degenerating intervertebral discs, cells were
      identified that formed a distinctive cocoon of encircling pericellular ECM.
      Immunohistochemical studies identified types I, II, III and VI collagen in these
      pericellular sites with diverse morphological features. Similar types of changes
      in the pericellular matrix were observed in both surgical specimens and control
      donor discs. Results indicate the need for future studies to address why such
      specialized matrix regions form around certain disc cells and to determine the
      consequences of these unusual matrix regions on annular lamellar organization and
      function.

PMID- 18074269
TI  - Comparison of historic Grubler dyes with modern counterparts using thin layer
      chromatography.
AB  - The aniline dye industry was created in 1856 when William Perkin prepared the
      dye, mauve, from coal tar. Following that discovery, several dye manufacturing
      businesses were formed in Western Europe, most successfully in Germany. It was to
      these companies that early investigators turned to obtain these new dyes for the
      developing field of biology. In 1880, Dr. Georg Grubler started a company in
      Germany to supply the needs of biologists. Grubler dyes developed a reputation
      for excellence. In the study reported here, 29 samples of 12 Grubler dyes were
      compared to modern counterparts using thin layer chromatography. The dyes studied
      were basic fuchsine, acid fuchsine, safranine, pyronine, aniline blue, ponceau,
      gentian violet, methylene blue, orange G, malachite green, and Sudan III and IV.
      I found that these early Grubler dyes closely resembled modern day counterparts;
      however, the use of synonyms was confusing and some of the fat stains were
      mislabeled by modern criteria. The chromatograms of some dyes exhibited smearing,
      probably representing multiple closely related dye species. The study of old dyes
      provides interesting comparisons with modern counterparts as the center of dye
      manufacturing is moving from Europe and the United States to Asia.

PMID- 18074270
TI  - Optimization of heterocyclic 4-hydroxystyryl derivatives for histological
      localization of endogenous and immunobound peroxidase activity.
AB  - Assisted by the development of light excitation and measuring techniques and the
      commercial availability of highly sensitive equipment, luminescent labels are
      sensitive detection tools for life sciences research. By contrast to a wide
      variety of well established chromogenic techniques, fluorescent labels for
      detecting peroxidase (PO) have been confined to only a few substrates. We
      describe here novel fluorescent substrates of PO derived from heterocyclic 4
      hydroxy styrenes as useful tools for detecting endogenous and exogenous targets
      in fixed cells and tissues. Excellent localization, high staining sensitivity,
      outstanding photostability, and exceptionally low background staining were
      achieved by optimizing the substrate through chemical synthesis.
      Structure/staining behavior relationships are discussed. By contrast to tyramine
      fluorochrome conjugates employed in the catalyzed reporter deposition (CARD)
      technique, reporting and anchoring functions are no longer separated.
      Consequently, enzymatic cross-linking of the substrate yields an altered
      fluorochrome with different properties. Spectral properties and anchoring
      capability are interdependent and influenced by environmental effects and pH. We
      screened overall staining capability of 4-hydroxy styryl derivatives using an
      iterative semi-empirical approach, and ascertained optimal substitution patterns
      for high PO staining specificity and high fluorescence response. Reliable
      staining performance was achieved with alkyl chains of short or medium length at
      the positively charged nitrogen, whereas introducing polar groups often impaired
      the staining specificity of PO. Catalytic cross-linking of heterocyclic 4-hydroxy
      styryl derivatives is a promising approach for permanent fluorescent staining of
      PO in fixed cells and tissues, and complements the CARD technique. Histochemical
      and immunohistochemical applications are presented using conventional and
      confocal fluorescence microscopes with different excitation sources. Spectral
      properties of selected stains are discussed. Novel stains also are of potential
      interest as "reactive-tracers" for living cells under multi-photon laser
      excitation conditions, because they exhibit pronounced nonlinear optical
      properties.

PMID- 18074271
TI  - Microchambers for inverted microscopes.
AB  - The designs for two microchambers, non-flow and flow, for inverted microscopes
      are described. These chambers are intended to study dynamic processes in living
      cells. The chambers described are made completely of a glass. An advantage of the
      flow chamber is the possibility of making simple changes in its internal space.
      It is dismantled easily to allow careful cleaning. This is especially important
      when working with toxic substances.

PMID- 18074272
TI  - Mapping cynomolgus monkey MHC class I district on chromosome 6p13 using pooled
      cDNAs.
AB  - The cynomolgus monkey (Macaca fascicularis) is a frequently used animal model for
      studying human diseases, especially immune related ones. For a better
      understanding of its major histocompatibility complex (MHC) class I district
      chromosome location, we selected seven cDNA clones as probes for fluorescence in
      situ hybridization (FISH) from a lymphocyte cell line cDNA library. Expressed
      sequence tags (ESTs) from these clones were assembled into three clusters and
      annotated Mafa-A and Mafa-B genes. Further bioinformatics analysis shows that
      they had multiple duplications spanning approximately 2.8 Mb on the rhesus
      macaque MHC class I district. Using the FISH technique, we mapped the seven
      pooled cDNA clones to the short arm of the cynomolgus monkey chromosome 6 on
      6p13. To our knowledge, this is the first report of the location of cynomolgus
      monkey MHC class I district. Using pooled adjacent cDNAs as probes also allows
      affordable, specific genome region mapping research.

PMID- 18074273
TI  - Immunohistochemical staining of inflammation and an artifact.

PMID- 18074277
TI  - Assessment of Hg contamination and exposure to miners and schoolchildren at a
      small-scale gold mining and recovery operation in Thailand.
AB  - Gold extracted by Hg-amalgamation process, which can cause both health and
      environmental problems, is widespread in South East Asia including Myanmar, Laos,
      Cambodia, and Thailand. Small-scale gold mining operations have been carried out
      since the year 2000 in Phanom Pha District, Phichit Province, Thailand. Since no
      data is available for evaluating Hg exposure, an investigation of mercury (Hg)
      contamination and exposure assessment was carried out at this mine site.
      Environmental monitoring illustrated the total Hg in water was as high as 4
      microg/l while Hg in sediment ranged between 102 to 325 microg/kg dry weight.
      Both Hg deposition from the air (1.28 microg/100 cm(2)/day) and concentration in
      surface soil (20,960 microg/kg dry weight) were elevated in the area of
      amalgamation. The potential of Hg exposure to miners as well as to schoolchildren
      was assessed. The concentrations of Hg in urine of 79 miners who were directly
      (group I) or indirectly (group II) involved in the gold recovery operation were
      32.02 and 20.04 microg/g creatinine, respectively, which did not exceed
      regulatory limits (35 microg/g creatinine). Hair Hg levels in both groups (group
      I and group II) also were not significantly higher than the non-exposed group. In
      terms of risk factors, gender and nature of food preparation and consumption were
      the two significant variables influencing the concentration of Hg in urine of
      miners (P < 0.05). A hazard quotient (HQ) was estimated based on the inorganic Hg
      exposure of individual miners. The HQ values of group I were in a range 16 to 218
      times higher than the safety level set as 1. By comparison the group II HQ index
      was very low (0.03-0.39). The miners in group I who worked and ate food from this
      area experienced potentially high exposure to Hg associated with the mining
      process. In a second Hg exposure assessment, a group of 59 schoolchildren who
      attended an elementary school near the gold mine site was evaluated for Hg
      exposure. A slightly higher Hg urine concentration was detected in group I and
      group II (involved and not involved in gold recovery) at average levels of 15.82
      and 9.95 microg/g creatinine, respectively. The average Hg values for both groups
      were below the established levels indicating no risk from Hg intake. Average Hg
      hair level in all schoolchildren (0.93 microg/g) was not significantly higher
      than reference group. There were two variables (gender and personal hygiene)
      which affected the concentration of Hg in urine of schoolchildren (P < 0.05). The
      result (HQ) also suggested that schoolchildren were not at risk (< 1).
      Schoolchildren involved in gold mining activities showed some indirect exposure
      to Hg from the adults working in mining area.

PMID- 18074278
TI  - Selected elements in Brown Birch Scaber Stalk Leccinum scabrum.
AB  - A survey of 26 metallic elements and metalloids such as Ag, Al, Ba, Ca, Cd, Co,
      Cr, Cs, Cu, Fe, Ga, Hg, K, Mg, Mn, Mo, Na, Ni, Pb, Rb, Sb, Se, Sr, Tl, V and Zn
      was carried out using ICP-MS, ICP-OES, HG-AAS and CV-AAS in the caps and stalks
      of edible mushroom Brown Birch Scaber Stalk collected from two lowland and one
      mountain sites in Poland. Ag, Al, Cd, Cr, Cs, Cu, Fe, Hg, K, Mg, Mo, Pb, Rb, Se,
      V and Zn occurred in greater concentration in the caps than stalks of Brown Birch
      Scaber Stalk, and opposite situation was for Tl and Na. Brown Birch Scaber Stalk
      collected from the site in Sudety Mountains did contain Al, Ba, Cs, Fe, Ga, Ni,
      Pb, Sr and V in significantly greater concentration when compared to specimens
      collected from the lowland sites, and what imply on significance of geological
      origin and/or soil substrate pollution impacting on mineral composition of this
      mushroom species. The results provide useful environmental and nutritional
      baseline level information on mineral composition of Brown Birch Scaber Stalk
      from unpolluted sites.

PMID- 18074279
TI  - Mercury and its bioconcentration factors in King Bolete (Boletus edulis) Bull.
      Fr.
AB  - The total mercury content for a representative number of the carpophores of King
      Bolete from 13 sites across Poland averaged from 1.1 +/- 1.4 to 7.6 +/- 3.1
      microg/g dry matter in the caps (total variation between 0.02 and 14 microg/g
      dm), and from 0.82 +/- 0.71 to 3.8 +/- 1.8 microg/g dm in stalks (total variation
      between 0.03 and 6.7 microg/g dm). A top soil layer (0-10 cm) collected from the
      mushroom sampling sites showed mean mercury content at range from 0.02 +/- 0.01
      to 0.05 +/- 0.02 microg/g dm (total variation between 0.01 and 0.08 microg/g dm).
      King Bolete is effective mercury accumulator in the carpophores and
      bioconcentration factor (BCF) of this element in the caps ranged from 41 +/- 6 to
      130 +/- 39 (total variation between 13 and 170) and in the stalks were from 27 +/
      18 to 72 +/- 22 (total variation between 4.0 and 90). Based on a relatively
      large set of data on the total mercury concentrations obtained in this survey,
      and dataset available for King Bolete from various sites in Europe, it seems
      reasonable to state that the upper food hygienic limit for the total mercury
      content in this species collected from unpolluted (background) sites should not
      exceed 20 microg/g dm in a single cap or a carpophore, while on an average, per
      site or consignment, should not exceed 10 mug/g dm in the caps or the
      carpophores.

PMID- 18074280
TI  - Chemical composition of edible Macadamia nuts (Macadamia integrifolia) and impact
      of soil quality.
AB  - The distribution of eight selected elements (As, Ca, Cr, Cu, Fe, Mg, Mn and Zn)
      in edible Macadamia (Macadamia integrifolia) nuts from eight sampling sites in
      the south east coast region of South Africa is investigated. The levels of the
      elements in all the Macadamia nuts are found to be in the decreasing order of Mg
      > Ca > Fe > Zn > Cu > Cr > As. The exception is Mn, which exhibited large
      variability with concentrations in nuts ranging from 10.21 +/- 0.47 microg g(-1)
      to 216.4 +/- 0.4 microg g(-1). The impact of soil quality parameters: soil pH,
      cation exchange capacity, soil organic matter and elemental concentrations, as
      well as interactions in the soil on the elemental composition in the nuts are
      also studied. At the Ifafa site, south of Durban, typical elemental
      concentrations (in microg g(-1) dry weight) in the (nuts and soil) are Mg (4920
      and 4656), Ca (2169 and 6173), Fe (92 and 20200), Zn (52 and 30), Cu (20 and 49),
      Cr (2.0 and 69.0) and As (0.024 and 0.104). The maximum concentration of Mg in
      the nuts is observed to be 4956.1 +/- 92.8 microg g(-1), while that of As is
      below 0.058 +/- 0.003 microg g(-1). Ca and Mg levels in nuts are antagonistic.
      Further, when bioavailable levels of Fe, Cu and Zn in soil are low, the
      bioaccumulation factor for Fe in nuts is high. Although, the soil quality
      parameters have an influence on the elemental uptake by the Macadamia nut, the
      results show that uptake and distribution of metals in the nuts are primarily
      dependent on the plants inherent controls that ensure the physiological well
      being of the plant. Macadamia nuts prove to have good control on elemental uptake
      and are low in the toxic metals investigated.

PMID- 18074281
TI  - Pentachlorophenol oxidation rates in supercritical water.
AB  - The oxidation rate of pentachlorophenol, [C(6)HCl(5)O] which is used to control
      termites and as a general herbicide and also as the probable human's carcinogen,
      was investigated in an isothermal continuous tubular reactor under supercritical
      water oxidation (SCWO) conditions. The experiments were conducted at a
      temperature of 400-550 degrees C and a fixed pressure of 25 MPa, with a residence
      time that ranged from 6 s to 26 s. The conversion of PCP was monitored by
      analyzing total organic carbon (TOC) on the liquid effluent samples. The initial
      TOC concentrations of PCP were varied from 0.74 mmol/L to 2.91 mmol/L and the
      oxygen concentrations were varied from 0.46 mmol/L to 3.52 mmol/L. By taking into
      account the dependence of the oxidant and TOC concentration on the reaction rate,
      a global PCP oxidation rate was regressed from the data of 48 experiments, to a
      95% confidence level. The resulting activation energy was determined to be 43.56
      +/- 1.47 kJ/mol, and the pre-exponential factor was (1.92 +/- 0.46) x 10(2)
      L(1.16) mmol(-0.16) s(-1). The reaction orders for the PCP (based on TOC) and the
      oxidant were 0.74 +/- 0.02 and 0.42 +/- 0.05, respectively.

PMID- 18074283
TI  - The inflow of polonium (210)Po from Vistula river catchments area.
AB  - The activities of polonium (210)Po in Vistula unfiltered water samples, collected
      from November 2002 to November 2003, were measured using the alpha spectrometry.
      In winter, the highest concentration of (210)Po was in Vistula river water from
      Torun (2.72 +/- 0.04 Bq x m(-3)) and from the Wieprz river (5.46 +/- 0.07 Bq x m(
      3) [Bequerel per cubic metre]), and the lowest was in water from Nida river (0.59
      +/- 0.02 Bq x m(-3)). During spring, the highest concentration of (210)Po was
      observed in Vistula water collected in Deblin (5.98 +/- 0.03 Bq x m(-3)) and the
      lowest in water from the Narew river (1.20 +/- 0.12 Bq x m(-3)). In summer, the
      highest concentration of (210)Po was in Nogat river water collected in Malbork
      (3.18 +/- 0.04 Bq x m(-3)) and the Bzura river (5.30 +/- 0.02 Bq x m(-3)), the
      lowest in Wieprz river (0.49 +/- 0.09 Bq x m(-3)) and Vistula river water from
      Krakow (1.44 +/- 0.05 Bq x m(-3)). In autumn, the highest (210)Po concentration
      was in Bzura river (8.93 +/- 0.03 Bq x m(-3)), the lowest in Vistula water from
      Grudziadz (1.51 +/- 0.04 Bq x m(-3)), and Torun (1.89 +/- 0.05 Bq x m(-3)). The
      highest quantity of (210)Po was transported from Vistula catchments area to the
      Baltic Sea in spring and the lowest in summer. Annually, the southern Baltic Sea
      is enriched by about 73.7 GBq (210)Po (with Leniwka and Nogat rivers), with 71.6
      GBq going to Gdansk Bay and 2.1 GBq to Vistula Lagoon. The highest surface
      (210)Po runoff was observed in spring (to 1370 kBq x km(-2) x quarter(-1) for
      Dunajec catchment's area), the lowest in summer (for Nida catchment's area to 100
      kBq x km(-2) x quarter(-1)).

PMID- 18074282
TI  - Degradation of aromatic compounds and degradative pathway of 4-nitrocatechol by
      Ochrobactrum sp. B2.
AB  - The potential capacity of a soil methyl parathion-degrading bacterium strain,
      Ochrobactrum sp. B2, for degrading various aromatic compounds were investigated.
      The results showed B2 was capable of degrading diverse aromatic compounds, but
      amino-substituted benzene compounds, at a concentration up to 100 mg L(-1) in 4
      days. B2 could use 4-nitrocatechol (4-NC) as a sole carbon and energy source with
      release of nitrite ion. The pathway for 4-NC degradation via 1,2,4-benzenetriol
      (BT) and hydroquinone (HQ) formation in B2 was proposed based on the
      identification and quantification of intermediates by gas chromatography-mass
      spectrometry (GC-MS), and high performance liquid chromatography (HPLC).
      Degradation studies carried out on a plasmid-cured derivative showed that the
      genes for 4-NC degradative pathway was plasmid-borne in B2, suggesting that B2
      degrades both p-nitrophenol and 4-NC by enzymes encoded by genes on the same
      plasmid.

PMID- 18074284
TI  - Biodegradation of methyl tert-butyl ether by Methylibium petroleiphilum PM1 in
      poor nutrition solution.
AB  - In this study, degradation of methyl tert-butyl ether (MTBE) by resting cells of
      Methylibium petroleiphilum PM1 was performed in poor nutrition solution, major
      component of which was MTBE. It was found that the biomass was hard to increase
      in poor nutrition, and the MTBE degradation activity was enhanced by 4.65-fold
      when 1 mM of Ba(2+) was added into deionized water. It was also found that the
      MTBE degradation could be significantly improved by the dissolved oxygen level.
      All of 50 mg L(-1) MTBE could be degraded under aerobic condition, while only 5%
      was degraded under anaerobic condition by resting cells in poor nutrition
      solution after 12 h. In the above solution, the degradation of tert-butyl alcohol
      (TBA) was found to be faster than that of MTBE, which suggested that TBA
      degradation might not be the limiting step in MTBE metabolism. While in the poor
      nutrition solution with the mixture of MTBE and TBA, the addition of TBA did not
      affect MTBE degradation while MTBE inhibited TBA degradation weakly, which
      suggested that different and independent enzymes were responsible for degrading
      such compounds. The success of MTBE degradation by PM1 cells in real contaminated
      groundwater demonstrated its feasibility to biodegrade MTBE under poor
      environment, and it also indicated the great potential of MTBE bioremediation by
      entrapped cells in future application.

PMID- 18074285
TI  - Degradation of acid blue 40 dye solution and dye house wastewater from textile
      industry by photo-assisted electrochemical process.
AB  - In this paper, electrochemical and photo-assisted electrochemical processes are
      used for color, total organic carbon (TOC) and chemical oxygen demand (COD)
      degradation of one of the most abundant and strongly colored industrial
      wastewaters, which results from the dyeing of fibers and fabrics in the textile
      industry. The experiments were carried out in an 18 L pilot-scale tubular flow
      reactor with 70%TiO(2)/30%RuO(2) DSA. A synthetic acid blue 40 solution and real
      dye house wastewater, containing the same dye, were used for the experiments. By
      using current density of 80 mA cm(-2) electrochemical process has the capability
      to remove 80% of color, 46% of TOC and 69% of COD. When used the photochemical
      process with 4.6 mW cm(-2) of 254 nm UV-C radiation to assist the electrolysis,
      has been obtained 90% of color, 64% of TOC and 60% of COD removal in 90 minutes
      of processing; furthermore, 70% of initial color was degraded within the first 15
      minutes. Experimental runs using dye house wastewater resulted in 78% of color,
      26% of TOC and 49% of COD in electrolysis at 80 mA cm(-2) and 90 min;
      additionally, when photo-assisted, electrolysis resulted in removals of 85% of
      color, 42% of TOC and 58% of COD. For the operational conditions used in this
      study, color, TOC and COD showed pseudo-first-order decaying profiles. Apparent
      rate constants for degradation of TOC and COD were improved by one order of
      magnitude when the photo-electrochemical process was used.

PMID- 18074286
TI  - Heavy metal removal from industrial wastewater by clinoptilolite.
AB  - Clinoptilolite- a natural zeolite has been investigated for the removal of heavy
      metals from the wastewaters. A pyrex-glass column of 30 mm diameter and 600 mm
      height was used. The column was filled with the conditioned clinoptilolite of 0.5
      1 mm. In the first stage of the research, synthetic wastewater containing single
      cation 0.02 N and 0.04 N Cu and 0.02 N Fe and Zn solutions were passed through
      the column. Two liter of 0.02 N Cu and 750 ml of the 0.04 N Cu solution was
      treated with 100 percent removal efficiency. Clinoptilolite column was
      regenerated for the reuse when the removal efficiency decreased. The cation
      exchange capacities were calculated as 1.0663 and 1.5342 meq/g clinoptilolite for
      0.02 N and 0.04 N Cu solutions, respectively. In the second stage of this
      research, the same procedure was repeated with the actual wastewater samples of
      the equalization and the neutralization tanks of the Telka-Rabak Electrolytic
      Copper Industry. A volume of 1811 ml of the wastewater of the equalization tank
      and 180 ml of the neutralization tank wastewater, which had high concentrations
      of Ni, Zn, Cu and Fe, was treated with 100 percent efficiency. The cation
      exchange capacities of clinoptilolite for the wastewater of the equalization and
      the neutralization tanks for Cu were 0.4483 and 0.4274, respectively. It was
      observed that only one third of the single copper ion solutions were obtained
      with the actual wastewater having competing ions such as Zn, Fe and Ni. The
      experimental results also indicate that the clinoptilolite is an effective cation
      exchanger for the removal of the metals from the wastewater and the removal
      efficiency is higher when there is not ant competing ions.

PMID- 18074287
TI  - Effects of pressure drop and superficial velocity on the bubbling fluidized bed
      incinerator.
AB  - Since performance and operational conditions, such as superficial velocity,
      pressure drop, particles viodage, and terminal velocity, are difficult to measure
      on an incinerator, this study used computational fluid dynamics (CFD) to
      determine numerical solutions. The effects of pressure drop and superficial
      velocity on a bubbling fluidized bed incinerator (BFBI) were evaluated.
      Analytical results indicated that simulation models were able to effectively
      predict the relationship between superficial velocity and pressure drop over bed
      height in the BFBI. Second, the models in BFBI were simplified to simulate scale
      up beds without excessive computation time. Moreover, simulation and experimental
      results showed that minimum fluidization velocity of the BFBI must be controlled
      in at 0.188-3.684 m/s and pressure drop was mainly caused by bed particles.

PMID- 18074288
TI  - Substrate storage concepts in modeling activated sludge systems for tannery
      wastewaters.
AB  - In spite of a variety of model structures proposed for activated sludge systems,
      calibration of these models for industrial wastewaters still stands untouched. In
      the scope of this study, a conceptual framework for the application of ASM1, ASM3
      and 3 models, involving simultaneous growth and storage under dynamic conditions
      is presented and these models have been used for simulating
      biodegradation/tannery wastewaters. A comparative representation of the modeling
      results obtained with 5 different models is provided. The comparison of the
      simulation results showed that the possibility of describing the real case
      increases as the model gets more detailed. Although structured models are
      supposed to provide a better description of the dynamic behavior observed for
      tannery effluents, the insufficiency experienced in the experimental
      determination of all the storage products when complex substrate compositions are
      concerned, hindered the accurate determination of model coefficients.
      Furthermore, modeling results for different F/M ratios clearly emphasized the
      challenge in the definition of readily biodegradable COD. Process stoichiometry
      and wastewater fractionation should be defined cautiously with additional data in
      order to provide substantial basis for the evaluation of the respirometric
      response in batch tests for model calibration.

PMID- 18074289
TI  - Influence of mineral and organic components on copper, lead, and zinc sorption by
      acid soils.
AB  - Sorption isotherms were constructed for the sorption of Cu, Pb and Zn by the
      surface horizons of three soils [a Humic Cambisol (G1), a Haplic Podzol (G2) and
      an Umbric Gleysol (G3)] and by fractions obtained by sequential removal of
      organic matter and oxides. All were of L-type except the H-type isotherms
      recorded for sorption of lead by whole G2, and all were fitted well by the
      Langmuir model, with determination coefficients > 0.91. Langmuir equation
      parameter beta correlated well (r(2) = 0.985) with experimentally maximum
      sorption capacity. For all soils, metal sorption capacities decreased in the
      order Zn > Cu > Pb. Sorption by organic matter was one of the main contributions
      to total sorption. Sorption by oxides was generally most substantial in G1, which
      had the largest total oxides content, while the sorption of lead by G3 was
      attributable to its high Mn oxides content. The clayey residue contributed
      significantly to sorption of zinc by G1, and G3 (due to their respective
      vermiculite and gibbsite contents) and to sorption of copper by G1 due to its
      vermiculite content.

PMID- 18074291
TI  - The use of immunochemical and biosensor methods for occupational and
      environmental monitoring. Part I: introduction to immunoassays.

PMID- 18074293
TI  - Continuous measurement of peak hydrogen fluoride exposures in aluminum smelter
      potrooms: instrument development and in-plant evaluation.
AB  - The aluminum smelting process continuously evolves both sulfur dioxide (SO2) and
      hydrogen fluoride (HF) gases. The vast majority of these evolved gases are
      captured by local exhaust ventilation systems and transported to fume treatment
      centers. Any gas escaping the ventilation systems could create the potential for
      workplace exposures. Currently, there are no commercially available sensors that
      are capable of selectively measuring peak concentrations (< 10 sec) of HF in the
      presence of SO2. This measurement capability is critical for facilitating a
      better understanding of the etiology of respiratory health effects. This article
      presents the development and in-plant testing of a portable, tunable diode-based
      HF sensor that shows equivalent or improved performance relative to NIOSH Method
      7902 and is capable of measuring short-term personal peak HF exposure potentials
      in operating aluminum smelters.

PMID- 18074294
TI  - The use of immunochemical and biosensor methods for occupational and
      environmental monitoring. Part II: Immunoassay data analysis and
      immunobiosensors.

PMID- 18074295
TI  - Abstracts of the 2007 BASES (British Association of Sport and Exercise Sciences)
      Annual Conference. September 12-14, 2007. Bath, United Kingdom.

PMID- 18074296
TI  - Carbohydrate and carbohydrate + protein for cycling time-trial performance.
AB  - Carbohydrate intake during endurance exercise delays the onset of fatigue and
      improves performance. Two recent cycling studies have reported increased time to
      exhaustion when protein is ingested together with carbohydrate. The purpose of
      the present study was to test the hypothesis that ingestion of a carbohydrate +
      protein beverage will lead to significant improvements in cycling time-trial
      performance relative to placebo and carbohydrate alone. Thirteen cyclists
      completed 120 min of constant-load ergometer cycling. Thereafter, participants
      performed a time-trial in which they completed a set amount of work (7 kJ kg(-1))
      as quickly as possible. Participants completed four experimental trials, the
      first for familiarization and then three randomized, double-blind treatments
      consisting of a placebo, carbohydrate, and carbohydrate + protein. Participants
      received 250 ml of beverage every 15 min during the constant-load ride. Time
      trial performance for carbohydrate (37.1 min, s = 3.8) was significantly (P <
      0.05) faster than placebo (39.7 min, s = 4.6). Time-trial performance for
      carbohydrate + protein (38.8 min, s = 5.5) was not significantly different from
      either placebo or carbohydrate. Ingestion of a carbohydrate beverage during two
      hours of constant-load cycling significantly enhanced subsequent time-trial
      performance compared with placebo. The carbohydrate + protein beverage provided
      no additional performance benefit.

PMID- 18074297
TI  - The public perception of doping in sport in Switzerland, 1995-2004.
AB  - The article reports findings on the perception of doping and anti-doping policies
      from four representative population surveys carried out in 1995, 1998, 2001, and
      2004, as well as from a 2005 - 2006 survey of top-level athletes in Switzerland.
      The results show a growing public awareness for doping issues and increasing
      support for a comprehensive anti-doping strategy in Switzerland. The vast
      majority of the Swiss population and top-level athletes are strongly against
      doping and support a strategy that combines strict prohibition and sanctioning
      with informational and educational efforts. The perception of the doping issue
      and the strategic preferences in fighting doping stated by the public are largely
      in line with the current anti-doping strategy followed by the Swiss authorities.
      The results thus suggest a successful use of information resources by the
      authorities to create public awareness and to communicate its strategy.

PMID- 18074298
TI  - Effect of antioxidants and exercise on bone metabolism.
AB  - We examined the effects of antioxidant supplementation in association with
      progressive aerobic training on the bone metabolism of healthy elderly
      individuals. For 8 weeks, 13 participants (mean age 74 years) received vitamin C
      (500 mg) and vitamin E (100 mg) daily and participated in a supervised
      progressive aerobic training programme. After the 8 weeks, 25-hydroxyvitamin D
      and 1,25-dihydroxyvitamin D concentrations were increased significantly by 42.8%
      (P < 0.001) and 26.8% (P < 0.01) respectively, while parathyroid hormone
      concentration was decreased by 17.5% (p < 0.05). Of the bone markers, only bone
      alkaline phosphatase decreased, by 14.6% (P < 0.05). No variation was observed
      for ionized calcium, insulin-like growth factor-1 or insulin-like growth factor
      binding protein-3. Our findings suggest that 8 weeks of combined antioxidant
      supplementation and aerobic training modified vitamin D metabolism and
      parathyroid hormone concentration. These adaptations might counterbalance the
      unfavourable hormonal profile frequently observed in the elderly that predisposes
      them to accentuated age-related bone loss.

PMID- 18074299
TI  - Mechanical and EMG responses of the vastus lateralis and changes in biochemical
      variables to isokinetic exercise in endurance and power athletes.
AB  - Twelve endurance athletes and six power athletes performed fatiguing isokinetic
      knee flexions/extensions. Isokinetic torque was recorded during the exercise.
      Isometric torque, cortisol and lactate responses, electromyographic (EMG) mean
      power frequency, average rectified value, and conduction velocity were analysed
      before and after the isokinetic exercise to determine correlations between
      electrophysiological variables and mechanical performances and/or blood
      concentrations of biomarkers in the two groups of athletes. The EMG variables
      were estimated from signals recorded from the vastus lateralis in both voluntary
      and electrically elicited isometric contractions. Power athletes recorded higher
      values than endurance athletes for the following variables: pre-exercise
      isometric maximal voluntary contraction (MVC), isokinetic MVC, rate of mechanical
      fatigue during isokinetic contractions, pre - post exercise variations and
      recovery times of conduction velocity and mean power frequency, and lactate
      concentrations. Moreover, conduction velocity overshooting was observed in
      endurance athletes during the recovery phase after exercise. The correlation
      analyses showed that the higher the rate of mechanical fatigue, the higher the
      lactate production and the reduction in conduction velocity due to the exercise.

PMID- 18074300
TI  - Effects of nicotinamide adenine dinucleotide hydride on physical and mental
      performance.
AB  - The aim of this study was to assess the effects of nicotinamide adenine
      dinucleotide hydride (NADH) on maximal oxygen uptake (VO2max), maximal anaerobic
      running time, and mental performance. Eight men were exposed to a supplement
      treatment (30 mg NADH as ENACHI tablets per day) and to a placebo treatment, each
      of 4 weeks' duration, in a balanced, double-blind, and cross-over design. The two
      treatments were separated by a 14-week wash-out period. The results indicated
      that VO2max, maximal anaerobic running time, and the ability to concentrate were
      similar in the NADH and placebo conditions. There were also no differences in
      blood lactate, creatine kinase, reaction time or feelings of fatigue between the
      treatments. A counter-movement jump performed at rest and 2 min after the aerobic
      test differed significantly (P <or= 0.05) between the treatment conditions and
      was higher in the NADH group. In conclusion, the NADH supplementation for 4 weeks
      had no effects on VO2max, maximal anaerobic running time or mental performance.

PMID- 18074301
TI  - Effects of acute exercise on executive processing, short-term and long-term
      memory.
AB  - In the present study, we evaluated the effects of a brief bout of exercise on
      executive function, short-term memory, and long-term memory tests. Eighteen young
      adults (mean age 22.2 years, s = 1.6) performed a set-switching test, a Brown
      Peterson test, and a free-recall memory test before and after 40 min of moderate
      aerobic exercise on a cycle ergometer, and two control conditions. Exercise did
      not facilitate set switching or short-term memory, which suggests that exercise
      induced arousal does not influence executive function processes involved in the
      reconfiguration of information in working memory. Exercise did alter specific
      aspects of delayed long-term memory. Free recall of items in the primacy and
      recency portions of the word list declined following the rest and non-exercise
      conditions, but was maintained after exercise, which suggests that exercise
      induced arousal may facilitate the consolidation of information into long-term
      memory.

PMID- 18074303
TI  - Environmental hazards: evidence for effects on child health.
AB  - The human fetus, child, and adult may experience adverse health outcomes from
      parental or childhood exposures to environmental toxicants. The fetus and infant
      are especially vulnerable to toxicants that disrupt developmental processes
      during relatively narrow time windows. This review summarizes knowledge of
      associations between child health and development outcomes and environmental
      exposures, including lead, methylmercury, polychlorinated biphenyls (PCBs),
      dioxins and related polyhalogenated aromatic hydrocarbons (PHAHs), certain
      pesticides, environmental tobacco smoke (ETS), aeroallergens, ambient air
      toxicants (especially particulate matter [PM] and ozone), chlorination
      disinfection by-products (DBPs), sunlight, power-frequency magnetic fields,
      radiofrequency (RF) radiation, residential proximity to hazardous waste disposal
      sites, and solvents. The adverse health effects linked to such exposures include
      fetal death, birth defects, being small for gestational age (SGA), preterm birth,
      clinically overt cognitive, neurologic, and behavioral abnormalities, subtle
      neuropsychologic deficits, childhood cancer, asthma, other respiratory diseases,
      and acute poisoning. Some environmental toxicants, notably lead, ionizing
      radiation, ETS, and certain ambient air toxicants, produce adverse health effects
      at relatively low exposure levels during fetal or child developmental time
      windows. For the many associations supported by limited or inadequate
      epidemiologic evidence, major sources of uncertainty include the limited number
      of studies conducted on specific exposure-outcome relationships and methodologic
      limitations. The latter include (1) crude exposure indices, (2) limited range of
      exposure levels, (3) small sample sizes, and (4) limited knowledge and control of
      potential confounders. Important knowledge gaps include the role of preconceptual
      paternal exposures, a topic much less studied than maternal or childhood
      exposures. Large longitudinal studies beginning before or during early pregnancy
      are urgently needed to accurately measure and assess the relative importance of
      parental and childhood exposures and evaluate relatively subtle health outcomes
      such as neuropsychologic and other functional deficits. Large case-control
      studies are also needed to assess the role of environmental exposures and their
      interactions with genetic factors in relatively uncommon outcomes such as
      specific types of birth defects and childhood cancers. There is also an urgent
      need to accelerate development and use of biomarkers of exposure and genetic
      susceptibility in epidemiologic studies. This review supports the priority
      assigned by international agencies to relationships between child health and air
      quality (indoor and outdoor), lead, pesticides, water contaminants, and ETS. To
      adequately address such priorities, governments and agencies must strengthen
      environmental health research capacities and adopt policies to reduce parental
      and childhood exposures to proven and emerging environmental threats.

PMID- 18074304
TI  - Pesticide exposures and developmental outcomes: the epidemiological evidence.
AB  - Since the advent of DDT as an insecticide in the late 1930s, billions of
      kilograms of pesticide active ingredient have been sold in North America and
      around the world. In recent years, there has been a heightened public awareness
      of pesticides and child health and a number of epidemiologic studies linked pre-
      and postnatal exposures to pesticides to a number of adverse developmental
      outcomes, including fetal death, intrauterine growth restriction, preterm birth,
      and birth defects. Given this, it was felt prudent to critically appraise the
      evidence for periconceptual pesticide exposures and developmental outcomes. The
      epidemiological evidence for specific pesticide classes, families, and active
      ingredients were examined and summarized and recommendations were made for how to
      improve future studies in order to address the current pitfalls and gaps in the
      studies in this area. Many of the studies suffered from poor exposure estimation,
      relying on job title only and/or the exposure category "any pesticide" as a
      measure of exposure, and there was limited or inadequate evidence to support
      causality for all associations examined.

PMID- 18074305
TI  - Pesticides and childhood cancer: an update of Zahm and Ward's 1998 review.
AB  - Children are exposed to pesticides through a number of sources, including
      residential and agricultural applications. Parental occupational exposure to
      pesticides is also a concern because exposures occurring during pregnancy and
      carry-home residues also contribute to children's cumulative burden. A number of
      epidemiological studies consistently reported increased risks between pesticide
      exposures and childhood leukemia, brain cancer, neuroblastoma, non-Hodgkin's
      lymphoma, Wilms' tumor, and Ewing's sarcoma. An extensive review of these studies
      was published in 1998 (Zahm & Ward, 1998). Fifteen case-control studies, 4 cohort
      studies, and 2 ecological studies have been published since this review, and 15
      of these 21 studies reported statistically significant increased risks between
      either childhood pesticide exposure or parental occupational exposure and
      childhood cancer. Therefore, one can confidently state that there is at least
      some association between pesticide exposure and childhood cancer. However, an
      unambiguous mechanistic cause-and-effect relationship between pesticide exposure
      and childhood cancer was not demonstrated in these studies, and modifying factors
      such as genetic predisposition, rarely considered in the reviewed studies, likely
      play an important role. While the time window of exposure may be a crucial
      determinant for biological effects associated with pesticide exposure on
      children, studies have not contributed definitive information on the most
      vulnerable period. Accurate exposure assessment remains a challenge; future
      epidemiological studies need to assess gene-environment interactions and use
      improved exposure measures, including separate parental interviews, specific
      pesticide exposure questions, and semiquantitative exposure measures that can be
      used to confirm information obtained through questionnaires.

PMID- 18074306
TI  - Parental alcohol consumption and childhood cancers: a review.
AB  - The etiology of childhood cancers remains generally unknown. Given that the
      metabolites of alcohol are likely carcinogens and that leukemia, the most
      frequent childhood cancer, can arise in utero, the study of alcohol consumption
      as a potential risk factor for the development of childhood cancer is justified.
      This article summarizes the epidemiological evidence on the association between
      parental exposure to alcohol and the risk of childhood cancers. To do this, a
      thorough search of the literature from 1960 to 2003 using the PubMed database was
      carried out. It yielded 33 case-control studies published between 1982 and 2003,
      including 13 studies that considered paternal exposure in the preconceptional
      period. In 10 of the 33 studies at least 1 statistically significant risk
      increase was reported in relation with parental alcohol consumption; in 7 of
      these studies the increase was related to maternal consumption, whereas in 3
      studies, it was related to paternal consumption. The cancers most often found
      associated with parental drinking were leukemia, brain tumors, and neuroblastoma.
      A few studies also reported a protective effect with maternal exposure at modest
      levels. Inconsistencies in the results and the low risks reported do not suggest
      an association between childhood cancer and parental consumption of alcohol.
      However, before reaching any definitive conclusions, methodological issues need
      to be addressed in future studies, as well as the role of genetic susceptibility.
      Moreover, subtypes of specific cancers need to be studied separately.

PMID- 18074307
TI  - Toward an economic analysis of the environmental burden of disease among Canadian
      children.
AB  - There have been calls for increased investments in research in Canada to
      determine the extent of exposure and the associated health effects of
      environmental risks to child health. When allocating scare public health
      resources, decision makers often rely on cost-benefit analysis to determine
      whether specific expenditures will yield significant economic benefits by
      reducing adverse health outcomes. This article describes the elements required
      for an economic analysis of the environmental burden of disease among Canadian
      children. Such analysis would require reviewing the strength of the association
      between environmental exposures and specific adverse pregnancy outcomes and
      childhood diseases. Second, it would determine the prevalence of childhood
      diseases and conditions in order to estimate the total economic and social costs
      associated with the overall burden of childhood diseases in Canada. The next step
      is to determine how much of the overall burden of disease among Canadian children
      can be attributed to environmental exposures. Recent environmental burden of
      disease analyses in other jurisdictions have led to advancement in methodologies
      that could support this work in Canada. Finally, the economic and social costs
      attributable to the environmental burden of childhood diseases in Canada could be
      estimated. Estimates of the economic costs of environmentally related diseases
      can then be used to determine the appropriate level of investments in scientific
      research. This article argues for initial investments in establishing a
      biomonitoring program of children's and pregnant women's exposure to
      environmental chemicals, as well as a Canadian longitudinal cohort study on the
      environmental influences on child health and development.

PMID- 18074308
TI  - Regulatory and nonregulatory strategies for improving children's environmental
      health in Canada.
AB  - Epidemiological and toxicological studies established positive associations
      between environmental hazards and adverse child health outcomes, including
      cancer, learning disabilities, behavioral problems, developmental effects, low
      birth weight, and birth defects. The economic and societal costs associated with
      children's environmental health disorders were estimated to be substantial. The
      existence of knowledge gaps, lack of capacity, and the jurisdictional overlap of
      children's environmental health issues are some of the barriers that impede
      effective policy decision making. To improve children's environmental health and
      reduce economic and societal costs, current legislative frameworks could
      implement a series of amendments. The main federal, provincial, and municipal
      legislation used to protect children in Canada, either explicitly or implicitly,
      is reviewed. Recommendations for improving the existing framework for protecting
      and strengthening children's environmental health are proposed.

PMID- 18074309
TI  - Sonography of the thyroid--Part 1.

PMID- 18074311
TI  - Is there a seasonal variation in the frequency of gastroschisis?
AB  - PURPOSE: There have been conflicting reports on the incidence of gastroschisis
      and its seasonal variation. Studies have found an increased risk of gastroschisis
      in deliveries occurring in the winter months in the northern hemisphere. Other
      studies have not found a seasonal variation. To evaluate the existence of a
      seasonal variation in the incidence of gastroschisis in our patients, a
      retrospective database analysis was conducted. MATERIALS AND METHODS: Second and
      third trimester pregnancy screening was performed on 8031 patients between
      October 2001 und September 2005. Patients were evaluated throughout the year
      separately for their expected date of delivery and date of conception during the
      summer months (April-September) and the winter months (October-March). RESULTS:
      We diagnosed 17 fetuses having gastroschisis with a mean gestational age at
      diagnosis of 24 weeks (range 11-33). The number of second and third trimester
      screening examinations and the number of patients with an expected date of
      delivery was not different during summer and winter months, 3980 vs. 4051. The
      expected date of birth (corrected for early ultrasound measurement) of fetuses
      with gastroschisis was more common during the winter months (n=11) than during
      summer months (n=6). However, this difference is not statistically significant
      (p=0.21) as was also the case for the date of conception. CONCLUSION: There seems
      to be no seasonal variation in the frequency of gastroschisis depending on the
      estimated date of birth or date of conception.

PMID- 18074312
TI  - The type of arterial anastomosis influences hepatic hemodynamics and overall
      survival in liver graft recipients.
AB  - AIM: Evaluation of the influence of arterial anastomoses on hepatic hemodynamics
      and overall survival in liver graft recipients using color Doppler ultrasound.
      METHOD: 224 patients recruited retrospectively were divided into five groups
      according to arterial anastomoses: (1) common hepatic (CHA)/gastro duodenal, (2)
      CHA/CHA, (3) aorta/celiac trunc, (4) aorta/aorta, (5) more than one anastomosis.
      We compared maximum portal [(P)Vmax], systolic [(A)Vmax] and end diastolic
      [(A)Vmin] arterial velocities, resistance indexes(RI), spleen and liver size
      between the groups. We analyzed further in a multivariate analysis the influence
      of time elapsed since orthotopic liver transplantation, age of recipient and
      donor on significant parameters as well as the overall survival of the patients
      between the groups. RESULTS: Significant differences were found for: (A) Vmax
      between groups 2/4 (p<0.007) and 2/5 (p<0.010), (A) Vmin between groups 1/3
      (p<0.029) and 2/3 (p<0.015) and RI between the groups 1/3 (p<0.018) and 3/4
      (p<0.006). (A)Vmax and RI were only dependent on the type of arterial anastomosis
      (p<0.008 and p<0.014). The overall survival of the patients between the groups
      was significantly different (p<0.047). CONCLUSION: In this study we report the
      natural course of the mean values of portal and arterial velocities in different
      arterial reconstructions for the first time. (A) Vmax of the hepatic artery is
      identified as the most promising candidate prognostic parameter for the
      assessment of hemodynamic alterations after liver transplantation originating in
      the type of arterial anastomosis performed. The group of patients with more than
      one anastomosis had the lowest arterial (A) Vmax and simultaneously the lowest
      overall survival.

PMID- 18074313
TI  - Sonographic measurement of renal pelvis wall thickness as diagnostic criterion
      for acute pyelonephritis in adults.
AB  - PURPOSE: Inflammatory processes may increase the urothelial thickness of the
      renal pyelon. Purpose of the study was to assess sonographic measurement of
      pyelon wall thickness (PWT) in adult patients with acute pyelonephritis, chronic
      urinary tract infection (UTI) and indwelling ureteral stents. MATERIALS AND
      METHODS: Four study groups (acute pyelonephritis n=50, chronic UTI n=10,
      indwelling ureteral stents n=10, controls n=25) underwent renal ultrasonography
      (Acuson Seqouia, Mountain View, CA; 6 MHz Transducer). The renal pyelon was
      imaged in transverse and longitudinal planes. PWT measurements of patients with
      acute pyelonephritis were repeated after successful antibiotic treatment.
      RESULTS: Mean PWT in healthy controls was 1.0 mm+/-0.19. In patients with acute
      pyelonephritis, PWT was significantly increased to 2.9 mm+/-0.89 (p<0.001). PWT
      decreased significantly after antibiotic treatment to 1.4 mm+/-0.47 (p<0.001).
      Kidneys with indwelling stents presented with a PWT of 2.7 mm+/-0.68, kidneys
      with chronic UTI demonstrated a PWT of 2.8 mm+/-0.62. PWT in these patient groups
      was significantly greater than PWT in healthy volunteers (p<0.001). The
      interobserver agreement was excellent (p<0.001). CONCLUSION: PWT is a
      reproducible diagnostic criterion for acute pyelonephritis. Based upon our
      experience, we suggest a cut-off value of 2.0 mm to distinguish healthy kidneys
      from those with urothelium thickened by inflammation. PWT cannot be used to
      distinguish acute pyelonephritis from chronic inflammation of the urothelium.

PMID- 18074314
TI  - Percutaneous ultrasound-guided radiofrequency ablation (RFA) using saline
      perfused (wet) needle electrodes for the treatment of hepatocellular carcinoma-
      long term experience.
AB  - PURPOSE: For many reasons, resection of hepatocellular cancer (HCC) is not
      feasible in most cases. Radiofrequency (RFA) ablation has proven to be an
      effective minimally invasive alternative. It has been shown in ex vivo and animal
      trials that needle applicators perfused with isotonic saline solution could be an
      effective approach to enlarging the coagulation zone. However, long term survival
      data for the treatment of HCC are not yet available. MATERIALS AND METHODS: 37
      patients with a total of 64 histologically proven HCC with a maximum of 3 tumors
      of up to 6 cm and a contraindication to partial liver resection or orthotopic
      liver transplantation were treated with the Integra HiTT106 using wet monopolar
      single, wet bipolar double or wet triple needle electrodes. The mean HCC size was
      37.7 mm (range 15 to 60 mm). Follow-up examinations were performed 2 days and 1,
      3, 6, 9 months after RFA and every 6 months thereafter. The survival rate was
      calculated from the time of the first RFA session. RESULTS: 1, 2 and 5-year
      survival was 24/32 (75%), 14/31 (45%) and 3/21 (14%) overall; 18/19 (95%), 12/18
      (67%) and 3/10 (30%) for HCC Child A; and 6/13 (46%), 2/13 (15%) and 0/11 (0%),
      for HCC Child B. Complete remission was achieved in 86.5 % of the patients
      (total: 32 out of 37, multi-needle 18 / 21, single needle 14 / 16). Distant
      recurrence occurred overall in 20 out of 37 patients (54%), including 9 of 21
      treated with multiple needles (43% of patients) and 11 of the 16 patients treated
      with a single electrode (69%). The overall complication rate was 10.8%. Local
      recurrence was found for tumors measuring 3 cm-5 cm (n=28) in 7 out of 13 cases
      after single electrode RFA and in 1 out of 15 after multiple electrode treatment
      (significant, p=0.009). No significant difference between the single and multi
      needle group was found for tumors >5 cm and <3 cm. CONCLUSION: RFA using multiple
      wet electrodes shows promise as an effective method for treating inoperable HCC
      especially in cases with well-preserved liver function. Multiple electrodes seem
      to be superior to single electrodes with respect to the local recurrence rate for
      tumors between 3 and 5 cm.

PMID- 18074315
TI  - Reversal of P-glycoprotein-mediated drug efflux by eudesmin from Haplophyllum
      perforatum and cytotoxicity pattern versus diphyllin, podophyllotoxin and
      etoposide.
AB  - The present study focuses on eudesmin (bicyclic lignan, 0.15 % of dry leaves) and
      diphyllin (arylnaphthalene lignan, 0.1 % of dry roots), both isolated from H.
      perforatum Kar. et Kir, a Rutaceae species endemic to Uzbekistan. We first
      compared their specificity for cancer cells with those of etoposide and
      podophyllotoxin by screening their cytotoxicity on 3 healthy cell-lines and 7
      sensitive or resistant human solid cancer lines. We then tested their capacity to
      reverse P-glycoprotein-mediated multidrug resistance (MDR) by assaying dye and
      drug uptake in MDR1-transfected Madin-Darby canine kidney (MDCK-MDR1) and
      doxorubicine-resistant human breast carcinoma cells (MCF7/Dox). Eudesmin displays
      IC (50) values > 100 microM on all tested lines. Our data provide the first
      demonstration that this non-toxic lignan reverses Pgp-mediated drug efflux and
      supports the hypothesis that it may inhibit resistance mediated by MDR1 and MRP
      proteins. Even if its reversal activity is insufficient for clinical application,
      its capacity to accumulate [(3)H]-vinblastine in MDCK/MDR1 and MCF7/Dox cells
      suggests that eudesmin may positively affect the bioavailability and, thereby,
      the therapeutic potency of anticancer drugs in Pgp-overexpressing cells.
      Diphyllin exhibits IC (50) values ranging from 10 (- 6) to 10 (- 4) M. It is
      markedly less toxic than podophyllotoxin (IC (50) : 13 - 61 nM), but exhibits
      tumoricidal effects close to those of etoposide. Unfortunatly, it is 65-fold more
      toxic than etoposide on human primary fibroblasts. Consequently, it has no value
      as an anticancer drug. Its value as raw material for the hemisynthesis of
      anticancer drugs is discussed.

PMID- 18074316
TI  - Steroidal alkaloids from Veratrum japonicum with genotoxicity on brain cell DNA
      of the cerebellum and cerebral cortex in mice.
AB  - A new steroidal alkaloid ( 1), together with three known steroidal alkaloids ( 2 
      4), has been isolated from the roots and rhizomes of Veratrum japonicum (Baker)
      Loes. f.., their structures were established as neogermine ( 1), germine ( 2),
      germerine ( 3), and neogermbudine ( 4) by means of physicochemical properties and
      spectroscopic analysis. Compounds 1 - 4 exhibited genotoxicity on brain cells in
      mice by using single-cell gel electrophoresis (Comet assay).

PMID- 18074317
TI  - [Youngsters do research: prevention in childhood. The youngest authors in the
      history of the Deutsche Medizinische Wochenschrift (DMW)].

PMID- 18074318
TI  - [Nutrition and exercise of schoolchildren. Results of a cross-sectional study at
      the Lessing Gymnasium (secondary) school in Mannheim, Germany].
AB  - BACKGROUND AND OBJECTIVES: During the last few years there have been many
      articles in various newspapers about the unhealthy nutrition of children. It was
      the aim of this study to find out about the state of nutrition and exercise among
      the children at our school, a Gymnasium (secondary or grammar school) in
      Mannheim, Germany. METHODS: We distributed questionnaires to 729 fellow pupils at
      the school to get some data/information about their exercise, nutrition and
      leisure activities. We developed a point-based system to record the quality of
      the food eaten; the time spent on sports, playing musical instruments; looking at
      television (TV) etc. or using the computer; and other leisure activities (e.g.
      reading, meeting friends, playing games). RESULTS: 84% of completed
      questionnaires were returned (98% of those sent to pupils in the lower forms).
      Food served at our school was reasonably good, but could have been improved by
      having a proper dining room or cafeteria. The situation regarding exercise tended
      to get worse in the younger pupils, because the school day has been lengthened.
      We found gender-related differences between school marks and other parameters.
      There was a positive relationship between good marks and a low [normal?] body
      mass index (BMI) and a negative effect on nutrition/exercise of hours spent
      watching TV or on the computer (PC). We also found a strong correlation in girls
      between school marks and their leisure. The number of points for wholesome meals,
      how much time the pupils spent on sports and music led to better school marks.
      Pupils of the lower grades exercised much less than older ones. CONCLUSION: Body
      weight index and their TV/computer time had similar effects in girls and boys. A
      low BMI correlated with better school marks, while high TV/PC time worsened them
      At our school relatively few pupils were overweight. Good nutrition and good
      amounts of exercise correlated positively with good marks. The amount of exercise
      taken by the pupils decreased as they advanced to the higher grades.

PMID- 18074319
TI  - [The origins of Christmas].

PMID- 18074320
TI  - [Christian beliefs and medicine: stations of a relationship].

PMID- 18074321
TI  - [Values, truth and good fortune].

PMID- 18074322
TI  - [The province of Homo patiens. Elias Canetti as a "medical author"].

PMID- 18074323
TI  - [The meaning of symptoms in medicine using A. Solschenizyn's "The Cancer Ward" as
      an example].

PMID- 18074324
TI  - [The "Fight over the Protein Minimum". The conflict between scientific nutrition
      teaching and food reform in 19th and 20th century Germany].
AB  - In 1877 the German physiologist and nutritionist Carl von Voit published diet
      parameters which included minimum intakes of carbohydrates, proteins and fats. As
      a minimum daily intake of protein Voit arrived at a figure of 118 g. This figure
      was questioned mainly by supporters of the so-called food reform, because the
      required protein intake would hardly be feasible without substantial meat
      consumption. To disprove this claim and to show that the vegetarian way of life
      was justified, reformers such as Mikkel Hindhede and Carl Rose conducted
      experiments demonstrating that the long-term adherence to diets with a daily
      protein intake of less than 30 g was possible without causing a negative protein
      balance. It was, however, only after the famines of the First World War that the
      concepts of the diet reformers met with greater interest. As they promised a
      better, from imports independent supply of food, the national socialist regime
      after 1933 made it the centre of a new food policy that aimed at autarky. Thus,
      the history of the "protein minimum" provides insights into effects and limits of
      nutrition research under the restrictions of economic requirements, moral
      considerations and prevailing traditions.

PMID- 18074325
TI  - [From skin to pluripotent stem cells: reprogramming of adult somatic cells].

PMID- 18074326
TI  - The patient's account of relapse and recovery in anorexia nervosa: a qualitative
      study.
AB  - OBJECTIVE: The purpose of this study was to explore the subjective accounts of
      weight-recovered female patients, who met DSMIV criteria for anorexia nervosa
      (AN), regarding their views of their illness following weight restoration.
      METHOD: Qualitative semi-structured interviews were administered to 15
      participants to ascertain their perspective of the factors that either
      contributed to their maintaining a healthy weight, or the factors involved in
      their having relapsed over the follow-up period. RESULTS: Qualitative analyses
      revealed six core categories: internal motivation to change, recovery as a work
      in progress, the perceived value of the treatment experience, developing
      supportive relationships, awareness and tolerance of negative emotion and self
      validation. DISCUSSION: This study provides valuable information about the way in
      which AN patients experience their illness and highlight the factors that help or
      hinder recovery. These findings may help enhance relapse prevention programs and
      potentially enhance our ability to identify and target those individuals at the
      greatest risk of relapsing.

PMID- 18074327
TI  - The needs of carers of patients with anorexia and bulimia nervosa.
AB  - OBJECTIVE: This study aims to assess the degree of distress and the need for
      support of carers of patients with anorexia and bulimia nervosa (BN). METHODS:
      Thirty-two carers filled out the General Health Questionnaire (GHQ-12) and the
      Burden Inventory (BI). In addition, they were interviewed with a semi-structured
      research interview, the Carers' Needs Assessment (CNA), to assess relevant
      problem areas as well as the needs for helpful interventions. Patients were
      interviewed with the Eating Disorder Examination (EDE) to assess the severity of
      the eating disorder. All patients met criteria for anorexia (n = 16) or BN (n =
      16) according to DSM-IV criteria. RESULTS: The mean duration of illness was 5.6
      years. The mean age of the carers was 41 years. Most of the carers were mothers
      or partners. In the CNA we found high numbers of problems as well as high numbers
      of needed interventions. The most frequently mentioned problem area was
      'disappointment caused by the chronic course of the illness, concerns about the
      patient's future' and the most frequently reported need for support was
      'counselling and support by a professional'. In three problem areas carers of
      persons suffering from anorexia nervosa (AN) reported significantly higher scores
      than carers of persons suffering from BN. CONCLUSIONS: Our results suggest that
      carers themselves have high levels of needs which are usually not addressed in
      clinical practice.

PMID- 18074328
TI  - Weight curves as predictors of short-term outcome in anorexia nervosa inpatients.
AB  - OBJECTIVE: The aim of the present study was to find factors that predict the
      short-term outcome of inpatients with anorexia nervosa (AN). METHOD: Female
      inpatients with AN (N = 100) were divided into treatment completers (N = 50) and
      drop-outs (N = 50). Using stepwise linear regression the relationship of
      demographic data, illness history and patterns of weight gain to BMI gain up to
      discharge were analysed. RESULTS: Among drop-outs, 69% of the variance in BMI
      gain up to discharge was explained by length of the first half of treatment
      (FHT), average weekly BMI gain and average weight loss during FHT. Among
      completers, 52% of the variance in BMI gain up to discharge was explained by BMI
      at admission and average weekly BMI gain during the second half of treatment
      (SHT). DISCUSSION: Weight curves offer important information about short-term
      outcome for patients with AN.

PMID- 18074329
TI  - Adverse relationship processes: the attempts of women with bulimia nervosa
      symptoms to fit the perceived ideal of intimate partners.
AB  - OBJECTIVE: This study drew together research on anxious attachment, self
      silencing, self-consciousness during sexual activity and bulimic symptoms.
      METHOD: A mixed community/university sample of 225 women aged 18-63 (M = 30.24,
      SD = 10.44) and involved in an intimate relationship completed questionnaires.
      RESULTS: Adverse relationship processes were significantly associated and each
      was also associated with bulimic symptoms. Self-consciousness during sexual
      activity was the best predictor of bulimic symptoms, followed by anxious
      attachment. Self-silencing was redundant when the other relationship processes
      were included in the regression. General psychopathology mediated the association
      between self-silencing and bulimic symptoms, and partially mediated associations
      between bulimic symptoms and both anxious attachment and self-consciousness
      during sexual activity. DISCUSSION: Women with bulimic symptoms attempt to change
      themselves by engaging in adverse processes in intimate relationships to meet the
      perceived expectations of their partners. Targeting these relationship processes
      in therapy might further add to the success of relationship-oriented treatments
      (e.g. interpersonal therapy).

PMID- 18074330
TI  - Thought suppression in obese and non-obese restrained eaters: piece of cake or
      forbidden fruit?
AB  - OBJECTIVE: This article examines thought suppression tendencies in restrained
      eaters. Furthermore, the dynamics between failing thought suppression and thought
      control strategies are explored. METHODS: One hundred and five overweight and
      normal-weight boys and girls (12-18 years) participated in a cross-sectional
      questionnaire-based study. A distinction was made between disinhibited restrained
      eaters (high restraint/high disinhibition), inhibited restrained eaters (high
      restraint/low disinhibition) and unrestrained eaters (low restraint) in both
      weight-groups. The Dutch Eating Behaviour Questionnaire (DEBQ) was used to select
      the different groups of (un)restrained eaters. The White Bear Suppression
      Inventory (WBSI) was employed to measure thought suppression and intrusions. The
      Thought Control Questionnaire (TCQ) was used to measure thought control
      strategies (distraction, punishment, reappraisal, worry, social control).
      RESULTS: The disinhibited restrainers obtained meaningfully higher scores on WBSI
      total, WBSI-thought suppression and WBSI-intrusion than the inhibited restrainers
      and unrestrained eaters in both weight groups. Those who scored high on WBSI
      total, obtained significantly higher scores on the TCQ subscales distraction,
      worry and punishment, than those who scored low on WBSI-total. DISCUSSION: The
      findings suggest that disinhibited restrainers, irrespective of their weight
      status, report a high tendency to suppress thoughts. Given Wegner's theoretical
      account, this may be associated with preoccupations and self-control
      difficulties.

PMID- 18074332
TI  - A two-matrix system for MALDI MS analysis of serine phosphorylated peptides
      concentrated by Fe3O4/Al2O3 magnetic nanoparticles.

PMID- 18074333
TI  - Evaluation of glycosylation and malonylation patterns in flavonoid glycosides
      during LC/MS/MS metabolite profiling.
AB  - Flavonoid conjugates constitute several classes of plant phenolic secondary
      metabolites including many isomeric compounds differing in the hydroxylation
      pattern and substitution of their rings with different groups such as alkyls,
      acyls or sugars. These compounds occur in plant tissues mainly as glycosides and
      in many cases it is necessary to have reliable and detailed information
      concerning the structure of these natural products. Our results were obtained
      using leaf extracts of Arabidopsis thaliana and Lupinus angustifolius in which
      different glycosides of flavones, flavonols and isoflavones are present. Analysis
      of collision-induced dissociation (CID)/MS/MS spectra of protonated [M + H](+),
      sodiated [M + Na](+) or deprotonated [M - H](-) molecules recorded during HPLC
      runs may bring needed information in this respect. However, registration of mass
      spectra of [M + Na](+) ions with a good efficiency is possible only after post
      column addition of a sodium acetate solution to the LC column eluate. The
      retention of sodium cation on the saccharidic parts of the molecule is observed
      after the CID fragmentation. In many cases, the location of this cation on the
      glycan attached to C-3 hydroxyl group of flavonol led to assignment of its
      structure. Additionally, the determination of the structure of the aglycone and
      of the sequence of the glycan part was made possible through the CID data
      obtained from the [M + H](+) and [M - H](-) ions. CID spectra show a different
      order of sugar elimination from hydroxyl groups at C-3 and C-7 in flavonol
      glycosides isolated from A. thaliana leaves and give sufficient information to
      discriminate flavonoid O-diglycosides from flavonoid di-O-glycosides.

PMID- 18074334
TI  - Binding constant determination of high-affinity protein-ligand complexes by
      electrospray ionization mass spectrometry and ligand competition.
AB  - We describe an approach for the determination of binding constants for protein
      ligand complexes with electrospray ionization mass spectrometry, based on the
      observation of unbound ligands competing for binding to a protein target. For the
      first time, dissociation constants lower than picomolar could be determined with
      good accuracy by electrospray ionization mass spectrometry. The presented
      methodology relies only on the determination of signal intensity ratios for free
      ligands in the low mass region. Therefore, all the advantages of measuring low
      masses with mass spectrometry, such as high resolution are preserved. By using a
      reference ligand with known binding affinity, the affinity of a second ligand can
      be determined. Since no noncovalently bound species are observed, assumptions
      about response factors are not necessary. The method is validated with ligands
      binding to avidin and applied to ligands binding to p38 mitogen-activated protein
      kinase.

PMID- 18074335
TI  - Synthesis of a new C(2)-symmetric chiral catalyst and its application in the
      catalytic asymmetric borane reduction of prochiral ketones.
AB  - A new C(2)-symmetric chiral catalyst 3,5-bis[(2S)-(hydroxy-diphenylmethyl)-
      pyrrolidin-1-ylmethyl]-1,3,4-oxadiazole was successfully synthesized by the
      reaction of 2,5-dichloromethyl-1,3,4-oxadiazole with (S)-alpha,alpha-diphenyl-2
      pyrrolidinemethanol, and applied to the catalytic asymmetric reduction of
      prochiral ketones with borane. When the catalyst loading was 1 mol %,
      enantiomeric excesses of up to 86.8% and 94.5% were observed in reduction of
      aromatic and alpha-halo ketones, respectively.

PMID- 18074336
TI  - Comparative studies on pharmacokinetic fates of tetrahydropalmatine enantiomers
      in different chemical environments in rats.
AB  - Tetrahydropalmatine (THP) is the active component in Rhizoma corydalis and the
      medicine Yuanhu-Baizhi (YB), which consists of Rhizoma corydalis and Radix
      angelicae dahuricae. The aim of this work was to compare pharmacokinetic features
      of THP enantiomers in rats dosed with racemic THP (rac-THP), Rhizoma corydalis,
      or YB extracts. A single dose of rac-THP (5 mg kg(-1)) or extracts of Rhizoma
      corydalis and YB (both equivalent to 5 mg kg(-1) of rac-THP) was given orally to
      three groups of Sprague-Dawley rats, respectively. Blood samples were collected
      periodically and plasma concentrations of THP enantiomers were determined using
      an achiral-chiral high-performance liquid chromatographic (HPLC) method
      previously reported, with some modifications. The C(max) ratio (-/+) of THP was
      2.91, 1.38, and 1.19, and the AUC(0 approximately infinity) ratio (-/+) of THP
      was 2.84, 1.50, and 1.35 in rats after dosed with rac-THP, extracts of Rhizoma
      corydalis and YB, respectively. The mean AUC(0 approximately infinity) and C(max)
      of (+)-THP dosed with YB extracts were 0.652 +/- 0.30 microg h ml(-1) and 0.148
      +/- 0.09 microg ml(-1), significantly higher (P < 0.05) than those dosed with rac
      THP and Rhizoma corydalis extracts. The mean AUC(0 approximately infinity) and
      T(max) of rac-THP dosed with YB extracts were 1.500 +/- 0.56 microg h ml(-1) and
      2.12 +/- 1.1 h, significantly higher (P < 0.05) than those dosed with rac-THP or
      Rhizoma corydalis extracts. These findings suggested the stereoselectivity in
      pharmacokinetics of THP enantiomers in rats was decreased when dosed in plant
      form, while the AUC(0 approximately infinity) of rac-THP increased when YB
      extracts were dosed, confirming the compatibility in drug combination of Rhizoma
      corydalis and Radix angelicae dahuricae.

PMID- 18074337
TI  - Candida rugosa lipase-catalysed kinetic resolution of 2-substituted-aryloxyacetic
      esters with dimethylsulfoxide and isopropanol as additives.
AB  - Candida rugosa lipase-catalysed hydrolysis of three different 2-substituted
      aryloxyacetic esters was performed in aqueous buffer containing dimethyl
      sulphoxide and isopropanol from 0 to 80% v/v as additives, in order to obtain an
      enhancement of the enantioselectivity. For 2-(p-chlorophenoxy)acetic acid and 2-n
      butyl-2-(p-chlorophenoxy)acetic acid ethyl esters, DMSO enhanced enzyme
      enantioselectivity more than IPA with an opposite enzymatic enantiopreference.
      The cosolvents moderately improved Candida rugosa lipase enantioselectivity for 2
      phenyl-2-(p-chlorophenoxy)acetic acid ethyl ester.

PMID- 18074338
TI  - Explicit ion, implicit water solvation for molecular dynamics of nucleic acids
      and highly charged molecules.
AB  - An explicit ion, implicit water solvent model for molecular dynamics was
      developed and tested with DNA and RNA simulations. The implicit water model uses
      the finite difference Poisson (FDP) model with the smooth permittivity method
      implemented in the OpenEye ZAP libraries. Explicit counter-ions, co-ions, and
      nucleic acid were treated with a Langevin dynamics molecular dynamics algorithm.
      Ion electrostatics is treated within the FDP model when close to the solute, and
      by the Coulombic model when far from the solute. The two zone model reduces
      computation time, but retains an accurate treatment of the ion atmosphere
      electrostatics near the solute. Ion compositions can be set to reproduce specific
      ionic strengths. The entire ion/water treatment is interfaced with the molecular
      dynamics package CHARMM. Using the CHARMM-ZAPI software combination, the implicit
      solvent model was tested on A and B form duplex DNA, and tetraloop RNA, producing
      stable simulations with structures remaining close to experiment. The model also
      reproduced the A to B duplex DNA transition. The effect of ionic strength, and
      the structure of the counterion atmosphere around B form duplex DNA were also
      examined.

PMID- 18074339
TI  - Thermodynamic and structural properties of methanol-water solutions using
      nonadditive interaction models.
AB  - We study bulk structural and thermodynamic properties of methanol-water solutions
      via molecular dynamics simulations using novel interaction potentials based on
      the charge equilibration (fluctuating charge) formalism to explicitly account for
      molecular polarization at the atomic level. The study uses the TIP4P-FQ potential
      for water-water interactions, and the CHARMM-based (Chemistry at HARvard
      Molecular Mechanics) fluctuating charge potential for methanol-methanol and
      methanol-water interactions. In terms of bulk solution properties, we discuss
      liquid densities, enthalpies of mixing, dielectric constants, self-diffusion
      constants, as well as structural properties related to local hydrogen bonding
      structure as manifested in radial distribution functions and cluster analysis. We
      further explore the electronic response of water and methanol in the differing
      local environments established by the interaction of each species predominantly
      with molecules of the other species. The current force field for the alcohol
      water interaction performs reasonably well for most properties, with the greatest
      deviation from experiment observed for the excess mixing enthalpies, which are
      predicted to be too favorable. This is qualitatively consistent with the
      overestimation of the methanol-water gas-phase interaction energy for the lowest
      energy conformer (methanol as proton donor). Hydration free energies for methanol
      in TIP4P-FQ water are predicted to be -5.6 +/- 0.2 kcal/mol, in respectable
      agreement with the experimental value of -5.1 kcal/mol. With respect to solution
      microstructure, the present cluster analysis suggests that the microscale
      environment for concentrations where select thermodynamic quantities reach
      extremal values is described by a bipercolating network structure.

PMID- 18074340
TI  - An improved pairwise decomposable finite-difference Poisson-Boltzmann method for
      computational protein design.
AB  - Our goal is to develop accurate electrostatic models that can be implemented in
      current computational protein design protocols. To this end, we improve upon a
      previously reported pairwise decomposable, finite difference Poisson-Boltzmann
      (FDPB) model for protein design (Marshall et al., Protein Sci 2005, 14, 1293).
      The improvement involves placing generic sidechains at positions with unknown
      amino acid identity and explicitly capturing two-body perturbations to the
      dielectric environment. We compare the original and improved FDPB methods to
      standard FDPB calculations in which the dielectric environment is completely
      determined by protein atoms. The generic sidechain approach yields a two to
      threefold increase in accuracy per residue or residue pair over the original
      pairwise FDPB implementation, with no additional computational cost. Distance
      dependent dielectric and solvent-exclusion models were also compared with
      standard FDPB energies. The accuracy of the new pairwise FDPB method is shown to
      be superior to these models, even after reparameterization of the solvent
      exclusion model.

PMID- 18074341
TI  - A Gibbs free energy correlation for automated docking of carbohydrates.
AB  - Thermodynamic information can be inferred from static atomic configurations. To
      model the thermodynamics of carbohydrate binding to proteins accurately, a large
      binding data set has been assembled from the literature. The data set contains
      information from 262 unique protein-carbohydrate crystal structures for which
      experimental binding information is known. Hydrogen atoms were added to the
      structures and training conformations were generated with the automated docking
      program AutoDock 3.06, resulting in a training set of 225,920 all-atom
      conformations. In all, 288 formulations of the AutoDock 3.0 free energy model
      were trained against the data set, testing each of four alternate methods of
      computing the van der Waals, solvation, and hydrogen-bonding energetic
      components. The van der Waals parameters from AutoDock 1 produced the lowest
      errors, and an entropic model derived from statistical mechanics produced the
      only models with five physically and statistically significant coefficients.
      Eight models predict the Gibbs free energy of binding with an error of less than
      40% of the error of any similar models previously published.

PMID- 18074342
TI  - Computational studies on the dimers and the thermal dimerization of
      norbornadiene.
AB  - In this study, 14 norbornadiene (NBD) dimers and the thermal dimerization
      mechanism were studied using the hybrid density functional theory (B3LYP) and the
      second-order multiconfigurational perturbation theory (CASPT2). In the process of
      dimerization, the biradical stationary points were located using the
      unrestricted, broken-spin, symmetry approach. The pathways were divided into
      eight parts to aid the analysis of their mechanisms. Our results indicated that
      the process for the formation of the cage-like
      heptacyclo[6.6.0.0.260.3130.411059.01014] tetradecane (HCTD, D14) is highly
      exothermic (92.15 kcal/mol), indicating that D14 is the most stable NBD dimer.
      However, the formation of D14 is very difficult to achieve kinetically because of
      a higher barrier in the thermal dimerization. On the contrary, the formation of
      exo-cis-exo (D5) is kinetically favorable, but thermodynamically unfavorable at
      higher temperature. Therefore, the combination of both thermodynamic and kinetic
      factors indicated that the formation of exo-exo (D9), which resembles the product
      of the pseudo-Diels-Alder addition, is most likely in the NBD dimerization.

PMID- 18074343
TI  - Complete basis set limit of Ab initio binding energies and geometrical parameters
      for various typical types of complexes.
AB  - Using basis-set extrapolation schemes for a given data set, we evaluated the
      binding energies and geometries at the complete basis set (CBS) limit at the
      levels of the second order Moller-Plesset perturbation theory (MP2) and the
      coupled cluster theory with singles, doubles, and perturbative triples
      excitations [CCSD(T)]. The systems include the hydrogen bonding (water dimer),
      aromatic interaction (benzene dimer), pi-H interaction (benzene-water), cation
      water, anion-water, pi-cation interaction (cation-benzene), and pi-anion
      interaction (anion-triazine). One extrapolation method is to exploit both BSSE
      corrected and BSSE-uncorrected binding energies for the aug-cc-pVNZ (N = 2, 3, 4,
      ...) basis set in consideration that both binding energies give the same CBS
      limit (CBS(B)). Another CBS limit (CBS(C)) is to use the commonly known
      extrapolation approach to exploit that the electron correlation energy is
      proportional to N(-3). Since both methods are complementary, they are useful for
      estimating the errors and trend of the asymptotic values. There is no significant
      difference between both methods. Overall, the values of CBS(C) are found to be
      robust because of their consistency. However, for small N (in particular, for N =
      2, 3), CBS(N)(B) is found to be slightly better for water-water interactions and
      cation-water and cation-benzene interactions, whereas CBS(N)(C) is found to be
      more reliable for bezene-water and anion-water interactions. We also note that
      the MP2 CBS limit value based on N = 2 and 3 combined with the difference between
      CCSD(T) and MP2 at N = 2 would be exploited to obtain a CCSD(T)/CBS value for
      aromatic-aromatic interactions and anion-pi interactions, but not for cationic
      complexes.

PMID- 18074344
TI  - Theoretical study on the OH + CH3NHCOOCH3 reaction.
AB  - The multiple-channel reactions OH + CH3NHC(O)OCH3 --> products are investigated
      by direct dynamics method. The optimized geometries, frequencies, and minimum
      energy path are all obtained at the MP2/6-311+G(d,p) level, and energetic
      information is further refined by the BMC-CCSD (single-point) method. The rate
      constants for every reaction channels, R1, R2, R3, and R4, are calculated by
      canonical variational transition state theory with small-curvature tunneling
      correction over the temperature range 200-1000 K. The total rate constants are in
      good agreement with the available experimental data and the two-parameter
      expression k(T) = 3.95 x 10(-12) exp(15.41/T) cm3 molecule(-1) s(-1) over the
      temperature range 200-1000 K is given. Our calculations indicate that hydrogen
      abstraction channels R1 and R2 are the major channels due to the smaller barrier
      height among four channels considered, and the other two channels to yield
      CH3NC(O)OCH3 + H2O and CH3NHC(O)(OH)OCH3 + H2O are minor channels over the whole
      temperature range.

PMID- 18074345
TI  - Time-averaged predictions of folded and misfolded peptides using a reduced
      physicochemical model.
AB  - Energy-based methods for calculating time-averaged peptide structures are
      important for rational peptide design, for defining local structure propensities
      in large protein chains, and for exploring the sequence determinants of amyloid
      formation. High-end methods are currently too slow to be practicable, and will
      remain so for the foreseeable future. The challenge is to create a method that
      runs quickly on limited computer resources and emulates reality sufficiently
      well. We have developed a simplified off-lattice protein model, incorporating
      semi-empirical physicochemical potentials, and combined it with an efficient
      Monte Carlo method for calculating time-averaged peptide structures. Reasonably
      accurate predictions are found for a set of small alpha-helical and beta-hairpin
      peptides, and we demonstrate a potential application in measuring local structure
      propensities in protein chains. Time-averaged structures have also been
      calculated for a set of small peptides known to form beta-amyloid fibrils. The
      simulations were of three interacting peptides, and in each case the time
      averaged structure describes a three-stranded beta-sheet. The performance of our
      method in measuring the propensities of small peptides to self-associate into
      possible prefibrillar species compares favorably with more detailed and CPU
      intensive approaches.

PMID- 18074346
TI  - Parameterization of Ca+2-protein interactions for molecular dynamics simulations.
AB  - Molecular dynamics simulations of Ca+2 ions near protein were performed with
      three force fields: GROMOS96, OPLS-AA, and CHARMM22. The simulations reveal
      major, force-field dependent, inconsistencies in the interaction between the Ca+2
      ions with the protein. The variations are attributed to the nonbonded
      parameterizations of the Ca+2-carboxylates interactions. The simulations results
      were compared to experimental data, using the Ca+2-HCOO- equilibrium as a model.
      The OPLS-AA force field grossly overestimates the binding affinity of the Ca+2
      ions to the carboxylate whereas the GROMOS96 and CHARMM22 force fields
      underestimate the stability of the complex. Optimization of the Lennard-Jones
      parameters for the Ca+2-carboxylate interactions were carried out, yielding new
      parameters which reproduce experimental data.

PMID- 18074347
TI  - Outcomes of breast cancer patients with and without BRCA1/2 mutations.

PMID- 18074348
TI  - Risks of cancer among a cohort of 23,935 men and women with osteoporosis.
AB  - Low hormone levels among persons with osteoporosis may decrease risk of some
      cancers. Other osteoporosis risk factors, such as smoking and alcohol
      consumption, however, may increase risk. As these deleterious factors are more
      often associated with osteoporosis diagnosed prior to age 70 years, cancer risk
      may be higher in these younger persons than in the general population. To examine
      this hypothesis, a cohort study of 23,935 persons with osteoporosis was conducted
      in Denmark. Patients hospitalized with osteoporosis between 1978 and 1993 were
      identified in the Danish Inpatient Register. Linkage to the Danish Cancer
      Registry identified all cancer outcomes through 2003. Standardized incidence
      ratios (SIR) and 95% confidence intervals (95%CI) were calculated to compare
      cancer incidence in the cohort with that in the general population. Persons
      diagnosed prior to age 70 years were at increased cancer risk (women: SIR = 1.11,
      95%CI = 1.04-1.19; men: SIR = 1.31, 95%CI = 1.13-1.50) due, in part, to increased
      risks of cancers of the buccal cavity, esophagus, liver, pancreas and lung.
      Persons diagnosed at ages 70 and older were at decreased risk (women: SIR = 0.91,
      95%CI = 0.87-0.96; men: SIR = 0.89, 0.77-1.01) due, in part, to decreased risks
      of breast, endometrial, colon, rectal and brain cancers in women and prostate
      cancer in men. These results suggest that risk factors associated with earlier
      onset osteoporosis may be associated with increased risk of cancer. Conversely,
      factors associated with later onset osteoporosis may be related to a decreased
      risk of cancer.

PMID- 18074349
TI  - Type IV collagen alpha6 chain-derived noncollagenous domain 1 (alpha6(IV)NC1)
      inhibits angiogenesis and tumor growth.
AB  - Type IV collagen is a major component of vascular basement membranes. The
      noncollagenous (NC1) domains of several alpha-chains of type IV collagen reveal a
      capacity to inhibit angiogenesis and tumor growth. Here, we demonstrate that the
      NC1 domain of the alpha6 chain of type IV collagen (alpha6NC1) is an endogenous
      inhibitor of angiogenesis and tumor growth. Recombinant alpha6NC1 inhibits human
      endothelial cell proliferation and neovascularization of Matrigel plugs in mice.
      The alpha6NC1 suppresses the growth of subcutaneously transplanted Lewis lung
      carcinoma and also spontaneous pancreatic insulinomas that develop in the
      Rip1Tag2 mice. Inhibition of tumor growth is associated with significantly
      diminished microvascular density. Collectively, our results demonstrate that
      alpha6NC1 is an endogenous inhibitor of angiogenesis and tumor growth.

PMID- 18074350
TI  - p38 MAPK, but not ERK1/2, is critically involved in the cytotoxicity of the novel
      vascular disrupting agent combretastatin A4.
AB  - Combretastatin A4 (CA4) is a novel vascular disrupting agent that has promising
      clinical efficacy because of its ability to inhibit microtubule assembly and
      subsequently disrupt tumor blood flow. In this study, we demonstrate that mitogen
      activated protein kinases (MAPKs) are critically involved in the cytotoxicity of
      CA4. CA4 stimulates both extracellular signal-regulated kinases (ERK1/2) and p38
      MAPK in the BEL-7402 hepatocellular carcinoma cell line in a time- and dose
      dependent manner. This stimulation is a result of CA4-induced microtubule
      disassembly, which is a reversible process. Reversibility of microtubule
      disassembly is evidenced by the ability of disassembled microtubules to
      reassemble just a few hours after CA4 treatment. p38 MAPK, but not ERK1/2,
      contributes to this microtubule reassembly following CA4 exposure, and only
      inhibition of p38 MAPK, but not ERK1/2, synergistically enhances CA4-induced
      G(2)/M cell cycle arrest. Consistent with this, p38 MAPK inhibitors such as
      SB203580 and SB202190 also synergistically enhance the cytotoxicity of CA4 in
      cells where p38 MAPK is activated by CA4. This enhancement appears to be specific
      for CA4 because the cytotoxicity of other microtubule-targeted agents such as
      paclitaxel, vinorelbine and colchicine was not affected by p38 MAPK inhibitors.
      These data indicate that p38 MAPK is a potential anticancer target and that the
      combination of CA4 with p38 MAPK inhibitors may be a novel and promising strategy
      for cancer therapy.

PMID- 18074351
TI  - NQO1 and NFE2L2 polymorphisms, fruit and vegetable intake and smoking and the
      risk of colorectal adenomas in an endoscopy-based population.
AB  - Both environment and genetics contribute to the pathogenesis and prevention of
      colorectal neoplasia. NAD(P)H: quinone oxidoreductase (NQO1) is a detoxification
      enzyme that is polymorphic and inducible. We investigated interactions between
      lifestyle factors and polymorphisms in NQO1 and its key regulatory transcription
      factor NFE2L2 in colorectal adenoma risk. The NQO1 c.609C>T and g.-718A>G and
      NFE2L2 g.-650C>A, g.-684G>A and g.-686A>G polymorphisms were determined among 740
      Dutch adenoma cases and 698 endoscopy-based controls. Dietary intake was assessed
      by food frequency questionnaire, other lifestyle information by questionnaire.
      The NQO1 609CT genotype was associated with a higher adenoma risk (OR 1.27, 95%
      CI 1.00-1.62) compared with the 609CC genotype, whereas the 609TT genotype was
      not (OR 1.03, 95% CI 0.56-1.88). The higher risk with the NQO1 609CT-genotype was
      seen among smokers (OR 1.96, 95% CI 1.40-2.76), but not among nonsmokers (OR
      0.91, 95% CI 0.62-1.35; interaction p = 0.030). Fruit and vegetable consumption
      did not protect smokers from adenomas and did not interact with the NQO1 609C>T
      polymorphism or the NFE2L2 polymorphisms. A higher adenoma risk seen with high
      fruit and vegetable consumption among NQO1 -718GG genotypes was absent among 
      718GA genotypes (interaction p = 0.071). Gene-gene interactions were observed
      between the NQO1 609C>T and NFE2L2 -686A>G polymorphisms (interaction p = 0.056)
      and between the NQO1 -718 G>A and NFE2L2 -650C>A polymorphisms (interaction p =
      0.013). IN CONCLUSION: the NQO1 609CT genotype is associated with increased
      adenoma risk among smokers, which is not diminished by high fruit and vegetable
      consumption. The observed gene-gene interactions may point to a role for NFE2L2
      polymorphisms in NQO1-related adenoma formation.

PMID- 18074352
TI  - Histone deacetylase inhibitor Helminthosporium carbonum (HC)-toxin suppresses the
      malignant phenotype of neuroblastoma cells.
AB  - The survival rate of children with advanced neuroblastoma (NB) is dismal despite
      intensive multimodal therapy. The limited efficacy and the frequent and serious
      side effects of currently used therapeutic regimens necessitate the development
      of new, less toxic treatment strategies. This study shows that the histone
      deacetylase inhibitor Helminthosporium carbonum (HC)-toxin suppresses the
      malignant phenotype of both established NB cell lines and primary NB cells with
      and without amplified MYCN at dosages lower than 20 nM. HC-toxin induces cell
      cycle arrest and apoptosis as well as neuronal differentiation and diminishes
      both colony formation and invasive growth. These cellular changes are accompanied
      by the transcriptional repression of cell cycle regulators of the retinoblastoma
      (RB) tumor suppressor network found at high levels in NBs with poor prognosis,
      like E2F-1 and its targets Skp2, N-myc, Mad2 and survivin. The levels of the
      hypophosphorylated active form of RB, and of cyclin-dependent kinase inhibitors
      including p15(INK4b), p16(INK4a), p21(cip1/waf-1) and p27(kip1) are increased. In
      conclusion, nanomolar doses of the HDACI HC-toxin cause a shift to a
      differentiated and benign phenotype of NB cells that is associated with an
      activation of the RB tumor suppressor network.

PMID- 18074353
TI  - Familial clustering of cancer at human papillomavirus-associated sites according
      to the Swedish Family-Cancer Database.
AB  - Familial aggregation of cervical cancer has been demonstrated previously, however
      aggregation of other human papillomavirus-associated anogenital, upper
      aerodigestive tract and skin cancers has not been fully characterized. The
      Swedish Family-Cancer Database, which contains reliable data on cancer incidence
      and nuclear family linkages for all residents of Sweden between 1958 and 2004,
      was used to calculate standardized incidence ratios (SIR) and 95% confidence
      intervals for offspring site-specific cancer risks according to site-specific
      cancer in sibling and parental probands. Offspring cancer risk was significantly
      increased when either a sibling or parent was affected at the same site for
      penile squamous cell carcinoma (SCC, SIR = 7.54), cervical adenocarcinoma (AC,
      SIR = 2.31), vulvar SCC (SIR = 2.27), skin SCC (SIR = 2.14), rectal AC (SIR =
      1.86), in situ cervical SCC (SIR = 1.80), invasive cervical SCC (SIR = 1.77) and
      upper aerodigestive tract SCC (SIR = 1.57). Significant aggregation on the order
      of 2-fold between anogenital cancers at different sites or histologies was also
      observed. In situ cervical SCC risk in offspring was strongly influenced by
      siblings affected with oropharyngeal SCC (SIR = 3.17) and tonsillar SCC (SIR =
      1.84). Familial skin SCC was largely unassociated with anogenital or upper
      aerodigestive tract cancer risk in offspring. These data suggest that common host
      factors exist among individuals affected with anogenital and upper aerodigestive
      tract cancers.

PMID- 18074354
TI  - Multiple end-point analysis reveals cisplatin damage tolerance to be a
      chemoresistance mechanism in a NSCLC model: implications for predictive testing.
AB  - Systemic chemotherapy is extensively used in cancer therapy, however, for many
      treatments' response rates are limited. Furthermore, certain regimens are
      frequently associated with significant morbidity and occasional mortality.
      Consequently, when alternative options exist, it is desirable to reserve a
      particular chemotherapy for those patients whose tumours will respond. Therefore,
      attention is turning to the development of techniques that could provide
      predictive information regarding a tumour's particular chemosensitivity, as a
      means of enhancing patient selection for that specific treatment. One approach
      has been to focus on measures of DNA damage formation and repair as being
      potentially predictive of cancer cell chemosensitivity, the premise being that
      higher levels of induced DNA damage (resulting from the chemotherapeutic agents)
      and/or deficiencies in DNA damage repair are indicative of greater sensitivity.
      In the present study we have investigated the Comet assay response of a panel of
      non-small cell lung cancer cell lines towards cisplatin and found an inverse
      correlation between sensitivity and damage formation resulting from this agent.
      Moreover, an inverse correlation was found between resistance and extent of
      damage repair. Further analysis of multiple alternate cellular end-points
      (including cell cycle analysis, apoptosis and gene expression changes) revealed
      cisplatin damage tolerance to be a chemoresistance mechanism in this model
      system. This study highlights damage tolerance mechanisms as potentially
      confounding factors in attempts to develop predictive tests based on measures of
      genotoxicity. To address this we would argue that a range of multiple end-points
      should be analysed to ascertain the "complete predictive picture".

PMID- 18074355
TI  - Trends in childhood cancer incidence in the U.S. (1992-2004).
AB  - BACKGROUND: The etiology of most pediatric neoplasms remains elusive. Examination
      of population-based incidence data provides insight regarding etiology among
      various demographic groups and may result in new hypotheses. The objective of the
      current study was to present updated information regarding childhood cancer
      incidence and trends in the U.S. overall and among demographic subgroups,
      including Asian/Pacific Islanders and Hispanics, for whom to the authors'
      knowledge trends have not been previously examined. METHODS: Data obtained by 13
      registries of the National Cancer Institute's Surveillance, Epidemiology, and End
      Results (SEER) program were evaluated to assess incidence and trends of common
      primary cancers diagnosed between 1992 and 2004 among children aged birth to 19
      years. Frequencies, age-adjusted incidence rates, and joinpoint regression
      results, including annual percent change (APC) in incidence rates (and 95%
      confidence intervals [95% CI]), were calculated. RESULTS: Between 1992 and 2004,
      a modest, nonsignificant increase in the average annual incidence rate (APC,
      0.4%; 95% CI, -0.1%-0.8%) was observed for all pediatric cancer diagnoses
      combined. There was a suggestion of an increase in leukemia (APC, 0.7%; 95% CI, 
      0.1%-1.5%), and acute lymphoblastic leukemia in particular (APC, 0.8%; 95% CI, 
      0.4%-1.9%), whereas rates for central nervous system tumors overall were stable
      (APC, -0.1%; 95% CI, -1.1%-1.0%); 2 joinpoints were observed for astrocytoma.
      Rate increases were noted for hepatoblastoma (APC, 4.3%; 95% CI, 0.2%-8.7%) and
      melanoma (APC, 2.8%; 95% CI, 0.5%-5.1%). Differences by demographic group (sex,
      age, and race/ethnicity) are also described. CONCLUSIONS: The observed trends
      reinforce an ongoing need for population-based surveillance and further etiologic
      studies.

PMID- 18074356
TI  - Hepatitis B virus precore protein augments genetic immunizations of the truncated
      hepatitis C virus core in BALB/c mice.
AB  - DNA immunization has been used to induce either humoral or cellular immune
      responses against many antigens, including hepatitis C virus (HCV). In addition,
      DNA immunizations can be enhanced or modulated at the nucleotide level. Genetic
      immunizations were examined in BALB/c mice through the use of plasmids and
      chimeric DNA constructs encoding HCV core proteins and hepatitis B virus (HBV)
      precore (preC) regions. Plasmids encoding the truncated HCV core induced potent
      humoral and cellular responses to HCV; pcDNA3.0A-C154 produced a stronger
      antibody response than pcDNA3.0A-C191 (P < 0.01) and pcDNA3.0A-C69 (P < 0.05).
      HBV preC enhanced the humoral and cellular immune responses of BALB/c mice to
      HCV; however, pcDNA3.0A-C69preC resulted in a weak cytotoxic T lymphocyte (CTL)
      response. In addition, the humoral and cellular immune responses to HCV of groups
      immunized with pcDNA3.0A-C154preC and pcDNA3.0A-C191preC plasmids were higher
      than those of groups immunized with pcDNA3.0A-C154 and pcDNA3.0A-C191. In vivo
      CTL responses verified that mice immunized with preC core fused DNAs showed
      significantly high specific lysis compared with mice immunized with HCV cores
      only (P < 0.01). In our study, pcDNA3.0A-C154preC led to the highest immune
      response among all DNA constructs. CONCLUSION: DNA that encodes truncated HCV
      core proteins may lead to increased immune responses in vivo, and these responses
      may be enhanced by HBV preC.

PMID- 18074357
TI  - Oxidized/misfolded superoxide dismutase-1: the cause of all amyotrophic lateral
      sclerosis?
AB  - The identification in 1993 of superoxide dismutase-1 (SOD1) mutations as the
      cause of 10 to 20% of familial amyotrophic lateral sclerosis cases, which
      represents 1 to 2% of all amyotrophic lateral sclerosis (ALS) cases, prompted a
      substantial amount of research into the mechanisms of SOD1-mediated toxicity.
      Recent experiments have demonstrated that oxidation of wild-type SOD1 leads to
      its misfolding, causing it to gain many of the same toxic properties as mutant
      SOD1. In vitro studies of oxidized/misfolded SOD1 and in vivo studies of
      misfolded SOD1 have indicated that these protein species are selectively toxic to
      motor neurons, suggesting that oxidized/misfolded SOD1 could lead to ALS even in
      individuals who do not carry an SOD1 mutation. It has also been reported that
      glial cells secrete oxidized/misfolded mutant SOD1 to the extracellular
      environment, where it can trigger the selective death of motor neurons, offering
      a possible explanation for the noncell autonomous nature of mutant SOD1 toxicity
      and the rapid progression of disease once the first symptoms develop. Therefore,
      considering that sporadic (SALS) and familial ALS (FALS) cases are clinically
      indistinguishable, the toxic properties of mutated SOD1 are similar to that of
      oxidized/misfolded wild-type SOD1 (wtSOD1), and secreted/extracellular misfolded
      SOD1 is selectively toxic to motor neurons, we propose that oxidized/misfolded
      SOD1 is the cause of most forms of classic ALS and should be a prime target for
      the design of ALS treatments.

PMID- 18074358
TI  - In utero exposure to mycophenolate mofetil: a characteristic phenotype?
AB  - Mycophenolate mofetil (MMF) is a widely prescribed immunosuppressive agent after
      solid organ transplantation. Potential teratogenic effects after in utero
      exposure to MMF in experimental studies and clinical observations in humans has
      been postulated in recent literature. However, a specific pattern of malformation
      has not been identified yet. We present a newborn patient, born to a recipient of
      renal transplantation, who became pregnant while taking MMF as immunosuppressive
      therapy. The newborn exhibited cleft lip and palate, bilateral microtia and
      atretic external auditory canals, chorioretinal coloboma, hypertelorism, and
      micrognathia. An extensive review of the literature documented six other cases
      with similar malformations after in utero exposure to MMF. A consistent pattern
      of malformations comprising cleft lip and palate, microtia and external auditory
      canals could be observed in five of the six cases. A different malformative
      pattern observed in one of the patients could be attributed to a different agent
      rather than MMF. The possible teratogenic effects of other immunosuppressive
      drugs, such as tacrolimus and prednisone, to which this patient was also exposed,
      are discussed herein. In addition, the differential diagnosis with other
      dysmorphic syndromes that can present with a similar phenotype, such as CHARGE
      syndrome, 18q deletion and hypertelorism-microtia-clefting (HMC) syndrome, is
      presented. We conclude that in utero exposure to MMF can cause a characteristic
      phenotype and propose the existence of a mycophenolate-associated embryopathy
      whose main features are: cleft lip and palate, microtia with atresia of external
      auditory canal, micrognathia and hypertelorism. Ocular anomalies, corpus callosum
      agenesis, heart defects, kidney malformations, and diaphragmatic hernia may be
      part of the phenotypic spectrum of MMF embryopathy. The human teratogenicity of
      MMF is reinforced by this report, and the current contraceptive recommendations
      about its use in fertile women are stressed.

PMID- 18074360
TI  - Parkinsonism and cognitive impairment following chronic exposure to potassium
      cyanide.

PMID- 18074359
TI  - Familial CHARGE syndrome and the CHD7 gene: a recurrent missense mutation,
      intrafamilial recurrence and variability.
AB  - CHARGE syndrome is an autosomal dominant condition that is caused by mutations in
      the CHD7 gene. Few familial cases of this syndrome have been reported and these
      were characterized by a wide clinical variability. We here report on five CHD7
      mutation positive families and comment on their clinical features. We observed
      somatic and germline mosaicism as well as parent-to-child transmission of non
      mosaic CHD7 mutations as causes of familial CHARGE syndrome. In one family with
      two affected sibs a somatic mutation was identified in lymphocytes of a
      clinically unaffected parent (2520G > A in exon 8). This is the second report of
      somatic CHD7 mosaicism in an unaffected parent. In two further families with
      affected siblings, we could not detect the mutation in parental lymphocytes
      suggesting germline mosaicism. The previously reported clinical variability was
      strikingly present in all five families. We find that alterations in CHD7 can
      result in a very mild phenotype, characterized by only a few minor symptoms of
      the CHARGE syndrome clinical spectrum. Such a mild phenotype was present in two
      families that shared the same 6322G > A missense mutation. These two families
      showed parent-to-child transmission. Phenotypically milder forms of CHARGE
      syndrome have a higher risk of transmission to multiple family members.

PMID- 18074361
TI  - Participation of the subthalamic nucleus in executive functions: An intracerebral
      recording study.
AB  - The objective of our work was to find whether the subthalamic nucleus (STN) is
      directly involved in cognitive activities, specifically in executive functions.
      Ten patients with idiopathic Parkinson's disease had P3 potentials recorded by
      externalized deep brain electrodes that were implanted in the STN or in its
      immediate vicinity. Two contacts of each electrode were positioned inside the STN
      according to clinical effect, perioperative microrecording, and stimulation. The
      P3 waves were recorded following the auditory stimulus in a standard oddball
      paradigm. They were compared with the P3 waves elicited from a protocol modified
      by a dual task with an increased demand on executive functions. The P3 potentials
      with a steep amplitude gradient evoked by the modified protocol were detected by
      the contacts in 8 of the 14 available electrodes, located either inside the STN
      or in its immediate vicinity. The modified protocol led to an increased latency
      of the P3 potential in 8 of 14 electrodes. No local field potentials of the
      standard P3 potentials were recorded. The P3 potentials related to the increased
      demand on executive functions were detected by the STN contacts known to have the
      best effect on Parkinsonian motor signs. This could suggest that the STN takes
      part in the executive function processing.

PMID- 18074362
TI  - Validity of spiral analysis in early Parkinson's disease.
AB  - Spiral analysis is an objective, easy to administer noninvasive test that has
      been proposed to measure motor dysfunction in Parkinson disease (PD). We compared
      overall Unified Parkinson Disease Rating Scale Part III scores to selected
      indices derived from spiral analysis in seventy-four patients with early PD (mean
      duration of disease 2.4 +/- 1.7 years, mean age 61.5 +/- 9.7 years). Of the
      spiral indices, degree of severity, first order zero crossing, second order
      smoothness, and mean speed were best correlated with total motor Unified
      Parkinson's Disease Rating Scale (UPDRS) score (all P < 0.01), and these indices
      showed a gradient across worsening tertiles of UPDRS (P < 0.05). Spiral indices
      also correlated with UPDRS ratings for the worst side and worst arm scores as
      well. The domains of bradykinesia, rigidity, and action tremor were correlated
      with first order crossing, second order smoothness, and mean speed, where as rest
      tremor was most highly correlated with degree of severity. This suggests that the
      spiral analysis may supplement motor assessment in PD, although further analysis
      of spiral metrics, a larger sample and longitudinal data should be evaluated.

PMID- 18074363
TI  - The Mayer-Rokitansky-Kuster-Hauser and gonadal dysgenesis anomaly in a girl with
      45,X/46,X,del(X)(p11.21).

PMID- 18074364
TI  - Acrocentric cryptic translocation associated with nondisjunction of chromosome
      21.
AB  - Down syndrome is the most frequent autosome aneuploidy in live newborns. It was
      recently proposed that pericentromeric cryptic translocations might be a cause of
      chromosome nondisjunction. We describe here a phenotypically normal subject with
      a cryptic translocation involving the short arms of chromosomes 13 or 21 and 22,
      who had a son with Down syndrome. Fluorescent in situ hybridization (FISH) on
      paternal metaphase chromosomes showed a chromosome 22 centromere positive for
      both 13/21 and 14/22 centromeric probes. The same probes hybridized on different
      and contiguous sites of chromatin fibers, eliminating cross-hybridization
      artifacts. This confirmed the presence of a cryptic translocation generating a
      dicentric chromosome 22: fib ish dic(21;22)(21 pter --> 21q10::22q10 --> 22
      qter)(D13/21Z1+;D14/22Z1+). Microsatellite STR segregation analysis confirmed the
      paternal origin of the additional chromosome 21 in the Down syndrome patient. To
      determine whether the father showed a higher-than-normal frequency of chromosome
      21 nondisjunction, FISH analysis of spermatozoa was performed using a sequence
      specific probe (21q22.13-q22.2). The frequency of disomy 21 spermatozoa was
      twofold higher in the cryptic translocation carrier as compared to normal
      subjects (P < 0.014), suggesting that the rearrangement favored the
      nondisjunction of chromosome 21. This is the first report associating a
      pericentromeric cryptic translocation of acrocentric chromosomes with the
      generation of aneuploidy, supporting the hypothesis that this type of
      rearrangement may contribute to abnormal chromosomal segregation.

PMID- 18074365
TI  - Cued task-specific training is better than exercise in improving sit-to-stand in
      patients with Parkinson's disease: A randomized controlled trial.
AB  - We examined whether 4 weeks of audio-visual (AV) cued task-specific training
      could enhance sit-to-stand (STS) and whether the treatment effects could outlast
      the treatment period by 2 weeks. Fifty-two subjects with PD completed the study.
      They were randomly allocated to receive 4 weeks of AV cued task-specific
      training, conventional exercise (Ex), or no treatment (control). Each subject was
      assessed before, at the end of 2 and 4 weeks of treatment, and 2 weeks after
      treatment ended. After 2 weeks of training, the AV group significantly increased
      the peak horizontal velocity (by 13%, P<0.01) when compared with the Ex group.
      After 4 weeks of training, AV group increased both peak horizontal and vertical
      velocities, respectively by 18% and 51%, and reduced the time taken to complete
      STS by 25%. These improvements were greater than those of the Ex group, who
      showed 8% (nonsignificant between-group) and 20% (P<0.05 between-group) increases
      respectively for peak horizontal and vertical velocities, and 10% decrease in
      movement time (P<0.05). Worth-noting is the improvements in AV group could be
      carried over to 2 weeks after treatment ended. These findings provided concrete
      evidence for the use of AV cued task-specific training to reeducate STS in
      patients with PD.

PMID- 18074366
TI  - Medication adherence and associated outcomes in medicare health maintenance
      organization-enrolled older adults with Parkinson's disease.
AB  - Maintenance of symptom control in Parkinson's disease (PD) requires continuous
      titration of medication and addition of multiple therapies over the course of the
      disease. Adherence to medication is vital to symptom control and key to
      maximizing the efficacy of existing therapies. However, adherence is compromised
      by a variety of factors, including motor symptoms, complex dosing regimens,
      multiple medications, and lack of patient/physician awareness of the impact and
      prevalence of suboptimal adherence. This retrospective, longitudinal cohort study
      assessed the prevalence of suboptimal adherence [measured as the medication
      possession ratio (MPR)] to PD medications, and its impact on the worsening of PD
      symptoms (measured as increase in monotherapy dose, augmentation of therapy, PD
      related emergency department visit, or hospitalization), in a Medicare Health
      Maintenance Organization population in the United States. Irrespective of the MPR
      threshold chosen, a high percentage of patients were categorized as suboptimally
      adherent to their PD medications, and patients with suboptimal adherence to their
      PD medications had higher risks of worsening of PD symptoms, compared with those
      who were adherent. Increased awareness of both the magnitude and impact of
      suboptimal adherence to PD medications, coupled with dosage simplification and a
      unified effort by healthcare professionals and patients, may improve adherence to
      PD medications and ultimately improve symptom control.

PMID- 18074367
TI  - Prolonged cortical silent period but normal sensorimotor plasticity in
      spinocerebellar ataxia 6.
AB  - Spinocerebellar ataxia 6 (SCA6) is a hereditary disease characterized by a
      trinucleotide repeat expansion in the CACNA1A gene and late-onset bilateral
      cerebellar atrophy. It is unclear if there is significant pathology outside of
      the cerebellum. We used transcranial magnetic stimulation to assess sensorimotor
      cortical circuits and cortical plasticity in 8 SCA6 patients and 8 age-matched
      controls. Behavioral performance was assessed using a rhythmic tapping task.
      Neurophysiological measures of SCA6 patients showed a prolonged cortical silent
      period (CSP) but normal MEP recruitment curve, short-latency afferent inhibition,
      long-latency afferent inhibition and ipsilateral silent period. Paired
      associative stimulation induction also increased motor-evoked potentials
      normally. SCA6 patients had greater variability with cued rhythmic tapping than
      normals and deteriorated when the cue was removed; in comparison, normal subjects
      had similar variability between cued and uncued rhythmic tapping. Analysis using
      a Wing-Kristofferson timing model indicated that both clock variance and motor
      delay variance were abnormal. Conclusion. In SCA6, the circuits for sensorimotor
      integration and the mechanisms for LTP-like plasticity in the sensorimotor cortex
      are unimpaired. A prolonged CSP in SCA6 just like in other cerebellar atrophies
      would suggest that this neurophysiological change typifies cerebellar
      dysfunction.

PMID- 18074368
TI  - Major gene and multifactorial inheritance of mandibular prognathism.
AB  - Mandibular prognathism typically shows familial aggregation. Various genetic
      models have been described and it is assumed to be a multifactorial and polygenic
      trait, with a threshold for expression. Our goal was to examine specific genetic
      models of the familial transmission of this trait. The study sample comprised of
      2,562 individuals from 55 families. Complete family histories for each proband
      were ascertained and the affection status of relatives were confirmed by lateral
      cephalograms, photographs, and dental models. Pedigrees were drawn using PELICAN
      and complex segregation analysis was performed using POINTER. Parts of some
      pedigrees were excluded to create one founder pedigrees, so the total N was
      2,050. Analysis showed more affected females than males (P = 0.030). The majority
      of the pedigrees suggest autosomal dominant inheritance. Incomplete penetrance
      was demonstrated by the ratio of affected/unaffected parents and siblings. The
      heritability of mandibular prognathism was estimated to be 0.316. We conclude
      that there is a major gene that influences the expression of mandibular
      prognathism with clear signs of Mendelian inheritance and a multifactorial
      component.

PMID- 18074369
TI  - Cytogenetic and array CGH characterization of an intrachromosomal complex
      rearrangement of 4q in a patient with a 4q-phenotype.
AB  - We report on a 3-year-old child who presented a de novo rearrangement of
      chromosome 4, detected on GTG banding and characterized by array CGH and FISH, as
      a complex intrachromosomal rearrangement with three deletions: del(q32.1q32.2),
      del(q33q34.1), del(q35.2), one tandem duplication dup(q34.3q35.1) and short
      normal regions in between. The study of karyotype-phenotype correlations in this
      and other patients with deletions of 4q suggests 4q33q34.1 as a candidate region
      for 4q-syndrome and for craniofacial development.

PMID- 18074370
TI  - Cytogenetic study of spontaneous abortions using semi-direct analysis of
      chorionic villi samples detects the broadest spectrum of chromosome
      abnormalities.
AB  - Conventional tissue culturing and karyotyping of spontaneous abortions has
      limitations such as culture failure, external contamination and selective growth
      of maternal cells. Molecular cytogenetic techniques such as FISH, QF-PCR, and CGH
      allow diagnosis on uncultured cells but are also limited as to the spectrum of
      cytogenetic abnormalities detected. We describe the cytogenetic findings in a
      series of 116 first trimester arrested pregnancies, obtained through chorionic
      villi sampling (CVS) and semi-direct analysis that avoids some of the long
      culture pitfalls such as maternal contamination, and compare our results with
      those that would have been obtained theoretically using molecular cytogenetic
      techniques. Samples were obtained by transcervical CVS from women with a
      diagnosis of missed abortion, most of them referred for cytogenetic prenatal
      diagnosis. Cytogenetic analysis was performed using semi-direct technique. A
      karyotype was obtained in 103 cases. Eighty-two abnormal karyotypes were found
      (80%), including 12 triploidies, 10 monosomies, 61 trisomies, and 9 structural
      abnormalities; a double abnormality being present in 10 cases. Between 10% and
      50% of our abnormal results would have been missed using the most common
      molecular cytogenetic techniques. Semi-direct analysis of CVS may still be
      considered as a comprehensive, reasonably rapid, cost-effective and reliable
      method for detecting the broadest spectrum of chromosome abnormalities in missed
      abortions.

PMID- 18074371
TI  - The treatment of displaced femoral neck fractures with vascularized great
      trochanter periosteal flap transposition in children.
AB  - In this study, we investigated the clinical outcome of the treatment of displaced
      femoral neck fractures with vascularized great trochanter periosteal flap
      transposition in children. There were 23 children with displaced femoral neck
      fractures. Using Delbet classification, there were 2 type I (transepiphyseal), 12
      type II (transcervical), and 9 type III (cervicotrochanteric). All the treatments
      were carried out with vascularized great trochanter periosteal flap
      transposition, and fixed by Kirschner needle or hollow screws. Both methods
      achieved healing and patients were followed from 9 months to 5 years, with
      average follow-up of 3 years. Avascular necrosis (AVN) of the femoral head
      occurred in three children; early closure of epiphysis occurred in one child; and
      restricted movement was seen in three children. According to Ratliff function
      assessment and Harris hip score, the results were: 17 excellent, 3 good, and 3
      poor. The excellent and good rates reached 87.1%. The vascularized greater
      trochanter periosteal flap transposition may accelerate the union of fractures,
      improve blood supply to the femoral head, and reduce the incidence rate of AVN.
      This flap is therefore an effective method for the treatment of displaced femoral
      neck fractures in children.

PMID- 18074372
TI  - Hemihyperplasia and discordant bone age in a patient with trisomy 8 mosaicism.

PMID- 18074373
TI  - Toriello-Carey syndrome phenotype and chromosome anomalies.

PMID- 18074374
TI  - Microanatomy and surgical relevance of the olfactory cistern.
AB  - All surgical approaches to the anterior skull base involve the olfactory cistern
      and have the risk of damaging the olfactory nerve. The purpose of this study was
      to describe the microanatomical features of the olfactory cistern and discuss its
      surgical relevance. In this study, the olfactory cisterns of 15 formalin-fixed
      adult cadaveric heads were dissected using a surgical microscope. The results
      showed that the olfactory cistern was situated in the superficial part of the
      olfactory sulcus, which separated the gyrus retus from the orbital gyrus. In
      coronal section, the cistern was triangular in shape; its anterior part enveloped
      the olfactory bulbs and was high and broad; its posterior part was medial
      superior to internal carotid artery and was also much broader. There were one or
      several openings in the inferior wall of the posterior part in 53.4% of the
      cisterns. The olfactory cistern communicated with the surrounding subarachnoind
      cisterns through these openings. The middle part of the olfactory cistern
      gradually narrowed down posteriorly. Most cisterns were spacious with a few
      fibrous trabeculas and bands between the olfactory nerves and cistern walls.
      However 23% of the cisterns were narrow with the cistern walls tightly encasing
      the olfactory nerve. There were two or three of arterial loops in each olfactory
      sulcus, from which long, fine olfactory arteries originated. The olfactory
      arteries coursed along the olfactory nerve and gave off many terminal branches to
      provide the main blood supply to the olfactory nerve in most cisterns, but the
      blood supply was in segmental style in a few cisterns. Moreover, the veins of the
      cistern appeared to be more segmental than the olfactory arteries in most
      cisterns. These results suggested that most olfactory cisterns are spacious with
      relatively independent blood supply, and it is reasonable to separate the
      olfactory tract with its independent blood supply from the frontal lobe by 1-2 cm
      in the subfrontal approach, the pterional approach, or anterior interhemispheric
      approach. However, in the minority of cases, separation of the olfactory tract is
      not safe because of the anterior origin of the olfactory arteries or segmental
      blood supply. It is difficult to separate the olfactory nerve without any damage
      to the olfactory nerve, even with very skilled hands.

PMID- 18074375
TI  - Focal hand dystonia in a patient with PANK2 mutation.

PMID- 18074376
TI  - A validation study of depressive syndromes in Parkinson's disease.
AB  - The validity, sensitivity, and specificity of depressive symptoms for the
      diagnosis of major depression, minor depression, dysthymic disorder, and
      subsyndromal depression in Parkinson's disease (PD) were examined. A consecutive
      series of 173 patients with PD attending a Movement Disorders Clinic underwent a
      comprehensive psychiatric and neurological assessment. The symptoms of loss of
      interest/pleasure, changes in appetite or weight, changes in sleep, low energy,
      worthlessness or inappropriate guilt, psychomotor retardation/agitation,
      concentration deficits, and suicide ideation were all significantly associated
      with the presence of the DSM-IV depressed mood criterion for major depression.
      The symptoms of changes in appetite, changes in sleep, low energy, low self
      esteem, poor concentration, and hopelessness were all significantly associated
      with the presence of the DSM-IV criterion of sad mood for dysthymic disorder.
      Thirty percent of our sample met DSM-IV diagnostic criteria for major depression,
      20% met diagnostic criteria for dysthymic disorder, 10% met diagnostic criteria
      for minor depression, and 8% met clinical criteria for subsyndromal depression.
      Patients with either major or minor depression had significantly more severe
      deficits in activities of daily living, more severe cognitive impairments, and
      more severe Parkinsonism than patients with either dysthymic disorder or no
      depression. This study provides validation to the DSM-IV diagnostic criteria for
      major depression and dysthymic disorder for use in PD. The categories of minor
      and subsyndromal depression may need further validation.

PMID- 18074377
TI  - Re: Miles & Takahashi paper on RhIg and autism.

PMID- 18074378
TI  - Rhinorrhea is increased in Parkinson's disease.
AB  - We have observed that rhinorrhea is increased in people with Parkinson's disease
      (PD) but only a single publication supports this. We performed two separate case
      control studies to assess the prevalence of rhinorrhea in PD in Rhode Island. One
      was cross-sectional and the other in consecutive de novo patients. We further
      questioned subjects as to whether rhinorrhea might be associated with olfactory
      impairment. We found that rhinorrhea affects about half of PD patients in Rhode
      Island, is an early feature, being present at the time of presentation, was
      significantly more common than in controls and was associated with self-perceived
      reduced olfaction. These observations confirm that rhinorrhea is a common problem
      and raise the questions as to whether some olfactory impairment found in PD could
      be confounded by rhinorrhea and also whether rhinorrhea may be a premotor
      symptom.

PMID- 18074379
TI  - A child with deletion (14)(q24.3q32.13) and auditory neuropathy.
AB  - An interstitial deletion in the middle and distal part of chromosome 14 is a rare
      chromosomal abnormality characterized by a wide spectrum of phenotypic
      manifestations. We present a patient with a nearly 20 Mb interstitial deletion of
      chromosome 14q24.3q32.13 determined by FISH, that is associated with minor
      dysmorphic features, developmental delay, absent speech and auditory neuropathy.
      The deleted region contains 130 known genes, among them 48 with reported function
      or association with human disease. The patient's phenotype is compared with
      interstitial deletions of the distal part of chromosome 14 reported previously.
      We hypothesize, that there is (are) a gene (genes) in the 14q32.11-q32.13 that is
      (are) important for the hearing process and for which haploinsufficiency can
      cause auditory neuropathy. Several genes in the region, among them calmodulin,
      chromogranin A, the goosecoid and FOXN3, can contribute to the observed
      phenotype. Detailed mapping in additional patients with 14q32 deletions and
      hearing loss could further define the candidate region.

PMID- 18074380
TI  - A girl with Down syndrome and partial trisomy for 21pter-q22.13: a clue to narrow
      the Down syndrome critical region.

PMID- 18074381
TI  - Fragile X full mutation alleles composed of few alleles: implications for CGG
      repeat expansion.
AB  - Southern analysis of the FMR1 repeat region has suggested that individuals with
      the full mutation usually carry a heterogeneous array of FMR1 alleles in somatic
      tissue that can range from 200 to more than 1,000 repeats. Our studies indicate
      that this heterogeneity is an artifact generated by ethidium bromide commonly
      used in Southern analysis. When analyzed in the absence of ethidium bromide,
      nearly all full mutation individuals carried only one to four major alleles and
      did not exhibit the heterogeneity often referred to as a "smear" in the
      literature. Full mutations in chorionic villi, however, exhibited much greater
      heterogeneity. Nine transmissions from mothers with full mutation alleles to
      offspring indicated that the full mutations continued to expand in transmission
      to the next generation. In contrast, analysis of leukocyte DNA from three full
      mutation males revealed no change in somatic full mutation alleles over many
      years. Our studies support the hypothesis that the FMR1 CGG repeat instability is
      limited to very early embryogenesis in the soma. These studies also have clinical
      importance because the omission of ethidium bromide will facilitate the diagnosis
      of females with full mutation alleles.

PMID- 18074382
TI  - Clinical characteristics of restless legs syndrome in end-stage renal failure and
      idiopathic RLS patients.
AB  - This study was done to identify the clinical characteristics of uremic restless
      legs syndrome (RLS). Consecutive uremic RLS patients (n = 15) and idiopathic RLS
      patients (iRLS; n = 20) were evaluated. The groups were compared with respect to
      their clinical course, subjective symptoms [using the Pittsburgh Sleep Quality
      Index (PSQI) and the International Restless Legs Syndrome Severity Scale (IRLS)],
      polysomnographic (PSG) variables, the results of the suggested immobilization
      test (SIT), and the drug doses used to treat RLS. The duration of the disorder
      was significantly shorter in the uremic RLS group than in the iRLS group. The
      PSQI and IRLS scores before treatment were higher in the uremic RLS group than in
      the iRLS group. The periodic leg movement index (PLM index) on PSG and the SIT
      index were also higher in the uremic RLS group (P < 0.001, respectively). The
      bromocriptine equivalent dose of dopaminergic agonists used to treat RLS was
      significantly higher in the uremic RLS group (P < 0.001). Uremic RLS appears to
      deteriorate faster and to become more severe than iRLS. Moreover, uremic RLS
      patients appear to have a decreased response to dopaminergic agonists.

PMID- 18074383
TI  - Glucocerebrosidase gene mutations are associated with Parkinson's disease in
      southern Italy.
AB  - Recent studies have reported an association between the glucocerebrosidase (GBA)
      gene and Parkinson's disease (PD). To elucidate the role of this gene in our
      population, we screened 395 PD patients and 483 controls from southern Italy for
      the N370S and the L444P mutations. We found 11 patients (2.8%) carrying a
      heterozygous mutant GBA allele, whereas only one control subject (0.2%) had a
      heterozygous substitution (P = 0.0018). These results strongly suggest that
      Italian carriers of a GBA mutation have an increased risk of developing PD.

PMID- 18074384
TI  - Different factors promote axonal regeneration of adult rat retinal ganglion cells
      after lens injury and intravitreal peripheral nerve grafting.
AB  - We have investigated the differential mediators of the neurotrophic effects of
      intravitreal peripheral nerve grafting and lens injury on adult rat retinal
      ganglion cells (RGC). Lens injury and intravitreal peripheral nerve grafting both
      stimulated RGC neurite growth in vitro and axon regeneration past the optic nerve
      lesion site in vivo concomitant with activation of retinal glia and invasion of
      macrophages into the eye. These observations, together with the results of
      coculture studies using a macrophage-free intact peripheral nerve segment, a
      macrophage-free intact lens, a macrophage-rich peripheral nerve segment, or a
      macrophage-rich injured lens in retinal cultures suggest that the stimulation of
      RGC axon regeneration by lens injury and intravitreal peripheral nerve grafting
      share a common macrophage-derived component overlain by distinct lens-derived and
      peripheral nerve-derived neurotrophic factors, respectively. RGC axon
      regeneration following lens injury and intravitreal peripheral nerve grafting was
      similar in vivo, correlating with similar retinal glia activation whereas, in
      vitro, the level of RGC neurite outgrowth was significantly higher following
      intravitreal peripheral nerve grafting compared with lens injury, concomitant
      with the presence of increased numbers of activated retinal glia. This suggests
      that in vivo RGC axon regeneration induced by lens injury and peripheral nerve
      grafting may be limited, in part, by factors derived from activated retinal glia.

PMID- 18074385
TI  - Neuroprotective effects of prostaglandin A(1) in rat models of permanent focal
      cerebral ischemia are associated with nuclear factor-kappaB inhibition and
      peroxisome proliferator-activated receptor-gamma up-regulation.
AB  - We have previously reported that prostaglandin A(1) (PGA(1)) reduces infarct size
      in rodent models of focal ischemia. This study seeks to elucidate the possible
      molecular mechanisms underlying PGA(1)'s neuroprotective effects against ischemic
      injury. Rats were subjected to permanent middle cerebral artery occlusion (pMCAO)
      by intraluminal suture blockade. PGA(1) was injected intracerebroventricularly
      (icv) immediately after ischemic onset. Western blot analysis was employed to
      determine alterations in IkappaBalpha, pIKKalpha, and peroxisome proliferator
      activated receptor-gamma (PPAR-gamma). Immunohistochemistry was used to confirm
      the nuclear translocation of nuclear factor-kappaB (NF-kappaB) p65 and the
      expression of PPAR-gamma. RT-PCR was used to detect levels of c-Myc mRNA. The
      contribution of PPAR-gamma to PGA(1)'s neuroprotection was evaluated by
      pretreatment with the PPAR-gamma irreversible antagonist GW9662. A brief increase
      in pIKKalpha levels and rapid reduction in IkappaBalpha were observed after
      ischemia. PGA(1) blocked ischemia-induced increases in pIKKalpha levels and
      reversed the decline in IkappaBalpha levels. Ischemia-induced nuclear
      translocation of NF-kappaB p65 was attenuated by PGA(1). PGA(1) also repressed
      the ischemia-induced increase in expression of NF-kappaB target gene c-Myc mRNA.
      Immunohistochemistry demonstrated an increase in PPAR-gamma immunoreactivity in
      the nucleus of striatal cells at 3 hr after pMCAO. Western blot analysis revealed
      that the expression of PPAR-gamma protein significantly increased at 12 hr and
      peaked at 24 hr. PGA(1) enhanced the ischemia-triggered induction of PPAR-gamma
      protein. Pretreatment with the irreversible PPAR-gamma antagonist GW9662
      attenuated PGA(1)'s neuroprotection against ischemia. These findings suggest that
      PGA(1)-mediated neuroprotective effect against ischemia appears to be associated
      with blocking NF-kappaB activation and likely with up-regulating PPAR-gamma
      expression.

PMID- 18074386
TI  - Maternal hyperthyroidism in rats impairs stress coping of adult offspring.
AB  - Given the evidence that maternal hyperthyroidism (MH) compromises expression of
      neuronal cytoskeletal proteins in the late fetal brain by accelerated neuronal
      differentiation, we investigated possible consequences of MH for the emotional
      and cognitive functions of adult offspring during acute and subchronic stress
      coping. Experimental groups consisted of male rat offspring from mothers
      implanted with osmotic minipumps infusing either thyroxine (MH) or vehicle (Ctrl)
      during pregnancy. Body weight and T4 level were monitored during the first 3
      postnatal months, and no differences were found with the controls. We analyzed
      hippocampal CA3 pyramidal neurons and dentate granular cell morphology during
      several postnatal stages and found increased dendritic arborization. On postnatal
      day 90 a modified subchronic mild stress (SCMS) protocol was applied to
      experimental subjects for 10 days. The Morris water maze was used before, during,
      and after application of the SCMS protocol to measure spatial learning. The tail
      suspension test (TST) and forced-swimming test (FST) were used to evaluate
      behavioral despair. The MH rats displayed normal locomotor activity and spatial
      memory prior to SCMS, but impaired spatial learning after acute and chronic
      stress. In both the FST and TST we found that MH rats spent significantly more
      time immobile than did controls. Serum corticosterone level was found to increase
      after 30 min of restraint stress, and corticotropin-releasing factor
      immunoreactivity was found to be increased in the central nucleus of the
      amygdala. Our results suggest that MH in rats leads to the offspring being more
      vulnerable to stress in adulthood.

PMID- 18074387
TI  - Descriptive epidemiology of Cornelia de Lange syndrome in Europe.
AB  - Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental
      retardation syndrome consisting of characteristic dysmorphic features,
      microcephaly, hypertrichosis, upper limb defects, growth retardation,
      developmental delay, and a variety of associated malformations. We present a
      population-based epidemiological study of the classical form of CdLS. The data
      were extracted from the database of European Surveillance of Congenital Anomalies
      (EUROCAT) database, a European network of birth defect registries which follow a
      standard methodology. Based on 23 years of epidemiologic monitoring (8,558,346
      births in the 1980-2002 period), we found the prevalence of the classical form of
      CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS
      prevalence at 1.6-2.2/100,000. Live born children accounted for 91.5% (97/106) of
      cases, fetal deaths 2.8% (3/106), and terminations of pregnancy following
      prenatal diagnosis 5.7% (6/106). The most frequent associated congenital
      malformations were limb defects (73.1%), congenital heart defects (45.6%),
      central nervous system malformations (40.2%), and cleft palate (21.7%). In the
      last 11 years, as much as 68% of cases with major malformations were not detected
      by routine prenatal US. Live born infants with CdLS have a high first week
      survival (91.4%). All patients were sporadic. Maternal and paternal age did not
      seem to be risk factors for CdLS. Almost 70% of patients, born after the 37th
      week of gestation, weighed <or=2,500 g. Low birth weight correlated with a more
      severe phenotype. Severe limb anomalies were significantly more often present in
      males.

PMID- 18074388
TI  - Clade-specific differences in neurotoxicity of human immunodeficiency virus-1 B
      and C Tat of human neurons: significance of dicysteine C30C31 motif.
AB  - OBJECTIVE: Human immunodeficiency virus-1 (HIV-1) causes mild to severe cognitive
      impairment and dementia. The transactivator viral protein, Tat, is implicated in
      neuronal death responsible for neurological deficits. Several clades of HIV-1 are
      unequally distributed globally, of which HIV-1 B and C together account for the
      majority of the viral infections. HIV-1-related neurological deficits appear to
      be most common in clade B, but not clade C prevalent areas. Whether clade
      specific differences translate to varied neuropathogenesis is not known, and this
      uncertainty warrants an immediate investigation into neurotoxicity on human
      neurons of Tat derived from different viral clades METHODS: We used human fetal
      central nervous system progenitor cell-derived astrocytes and neurons to
      investigate effects of B- and C-Tat on neuronal cell death, chemokine secretion,
      oxidative stress, and mitochondrial membrane depolarization by direct and
      indirect damage to human neurons. We used isogenic variants of Tat to gain
      insights into the role of the dicysteine motif (C30C31) for neurotoxic potential
      of Tat RESULTS: Our results suggest clade-specific functional differences in Tat
      induced apoptosis in primary human neurons. This study demonstrates that C-Tat is
      relatively less neurotoxic compared with B-Tat, probably as a result of
      alteration in the dicysteine motif within the neurotoxic region of B-Tat
      INTERPRETATION: This study provides important insights into differential
      neurotoxic properties of B- and C-Tat, and offers a basis for distinct
      differences in degree of HIV-1-associated neurological deficits observed in
      patients in India. Additional studies with patient samples are necessary to
      validate these findings.

PMID- 18074389
TI  - Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient
      with findings of Opitz G/BBB syndrome and Wolf-Hirschhorn syndrome.
AB  - Opitz G/BBB syndrome (OS) is a congenital midline malformation syndrome
      characterized by hypertelorism, hypospadias, cleft lip/palate,
      laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and
      cardiac defects. The X-linked form is caused by mutations in the MID1 gene, while
      no gene has yet been identified for the autosomal dominant form. Here, we report
      on a 15-year-old boy who was referred for MID1 mutation analysis with findings
      typical of OS, including apparent hypertelorism, hypospadias, a history of
      feeding difficulties, dysphagia secondary to esophageal arteria lusoria, growth
      retardation and developmental delay. No MID1 mutation was found, but subsequent
      sub-megabase resolution array CGH unexpectedly documented a 2.34 Mb terminal 4p
      deletion, suggesting a diagnosis of WHS, and a duplication in Xp22.31. Wolf
      Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving
      terminal chromosome 4p deletions, in particular 4p16.3. WHS is characterized by
      typical facial appearance ("Greek helmet facies"), mental retardation, congenital
      hypotonia, and growth retardation. While the severity of developmental delay in
      this patient supports the diagnosis of WHS rather than OS, this case illustrates
      the striking similarities of clinical findings in seemingly unrelated syndromes,
      suggesting common or interacting pathways at the molecular and pathogenetic
      level. This is the first report of arteria lusoria (esophageal vascular ring) in
      a patient with WHS.

PMID- 18074390
TI  - A teenage boy with late onset hemophagocytic lymphohistiocytosis with predominant
      neurologic disease and perforin deficiency.
AB  - Familial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessive
      disorder of cytotoxic cell function that results in abnormal proliferation of
      benign lymphocytes and histiocytes in response to infectious stimuli. FHLH
      generally occurs in very young children, and typically presents with fever,
      cytopenias, coagulopathy, lymphadenopathy, and hepatosplenomegaly. Central
      nervous system involvement occurs frequently and may precede the development of
      systemic symptoms by months to years. We report a case of an 18-year-old male
      with a 2-year history of symptoms attributed to a demyelinating disorder, who
      succumbed to rapidly progressive hemophagocyte lymphohistiocytosis. Post-mortem,
      two distinct perforin mutations were identified. We discuss the central nervous
      system and genetic findings in this unusual presentation of familial
      hemophagocytic lymphohistiocytosis.

PMID- 18074391
TI  - Exacerbation of blepharospasm associated with craniocervical dystonia after
      placement of bilateral globus pallidus internus deep brain stimulator.
AB  - To report a case of exacerbation of blepharospasm after bilateral globus pallidus
      internus (GPi) deep brain stimulator (DBS) placement. A 69-year-old male
      presented after bilateral GPi DBS placement for blepharospasm and craniocervical
      dystonia with worsening eyelid spasms and associated apraxia of lid opening
      (ALO). Numerous attempts to adjust DBS parameters were ineffective. Consequently,
      bilateral upper eyelid myectomy was performed. Myectomy surgery was free of
      complications. The patient had significant improvement of blepharospasm and ALO.
      Although early success has been reported with DBS placement in a small number of
      patients with focal dystonias, further studies and longer follow-up are needed to
      demonstrate whether this will prove to be a useful approach in the treatment of
      blepharospasm. Upper eyelid myectomy can provide an effective means for treating
      blepharospasm and associated ALO.

PMID- 18074392
TI  - Risk factors for sporadic Creutzfeldt-Jakob disease.
AB  - OBJECTIVE: Although surgical transmission of Creutzfeldt-Jakob disease (CJD) has
      been demonstrated, these iatrogenic cases account for only a small proportion of
      all CJD cases. The majority are sporadic CJD (sCJD) cases of unknown cause. This
      study investigated whether some cases classified as sCJD might have an
      unrecognized iatrogenic basis through surgical or other medical procedures
      METHODS: This study compared medical risk factors from 431 sCJD cases referred
      1998 to 2006 with 454 population control subjects. Possible geographic and
      temporal links between neurological and gynecological operations in 857 sCJD
      cases referred from 1990 to 2006 were investigated RESULTS: A reported history of
      ever having undergone surgery was associated with increased risk for sCJD (odds
      ratio, 2.0; 95% confidence interval, 1.3-2.1; p = 0.003). Increased risk was not
      associated with surgical categories chosen a priori but was confined to the
      residual category "other surgery," in which the increase in risk appeared most
      marked for three subcategories: skin stitches, nose/throat operations, and
      removal of growths/cysts/moles. No convincing evidence was found of links (same
      hospital, within 2 years) between cases undergoing neurosurgery or gynecological
      surgery INTERPRETATION: It is unlikely that a high proportion of UK sCJD cases
      are the result of transmission during surgery, but we cannot exclude the
      possibility that such transmission occurs occasionally. A study based on accurate
      surgical histories obtained from medical records is required to determine whether
      the increased risk associated with reported surgical history reflects a causal
      association or recall bias.

PMID- 18074393
TI  - Impaired intracortical inhibition in the primary somatosensory cortex in focal
      hand dystonia.
AB  - Somesthetic temporal discrimination (STD) is impaired in focal hand dystonia
      (FHD). We explored the electrophysiological correlate of the STD deficit to
      assess whether this is due to dysfunction of temporal inhibition in the
      somatosensory inhibitory pathway or due to dysfunction in structures responsible
      for nonmodality-specific timing integration. Eleven FHD patients and 11 healthy
      volunteers were studied. STD threshold was investigated as the time interval
      required for perceiving a pair of stimuli as two separate stimuli in time. We
      also examined the somatosensory-evoked potential (SEP) in a paired-pulse
      paradigm. We compared STD threshold and recovery function of SEP between the
      groups. STD thresholds were significantly greater in FHD than in healthy
      volunteers. The amount of P27 suppression in the 5 ms-ISI condition was
      significantly less in FHD. It was also found that the STD threshold and P27
      suppression were significantly correlated: the greater the STD threshold, the
      less the P27 suppression. Significantly less suppression of P27 with a lack of
      significant change in N20 indicates that the impairment of somatosensory
      information processing in the time domain is due to dysfunction within the
      primary somatosensory cortex, suggesting that that the STD deficit in FHD is more
      attributable to dysfunction in the somatosensory pathway.

PMID- 18074395
TI  - Cleavage of the human thyrotropin receptor by ADAM10 is regulated by thyrotropin.
AB  - The thyrotropin receptor (TSHR) has a unique 50 residue (317-366) ectodomain
      insertion that sets it apart from other glycoprotein hormone receptors (GPHRs).
      Other ancient members of the leucine-rich repeat G protein-coupled receptor
      (GPCR) (LGR) family do exhibit ectodomain insertions of variable lengths and
      sequences. The TSHR-specific insert is digested, apparently spontaneously, to
      release the ectodomain (A-subunit) leaving the balance of the ectodomain attached
      to the serpentine (B-subunit). Despite concerted efforts for the last 12 years by
      many laboratories, the enzyme involved in TSHR cleavage has not been identified
      and a physiologic role for this process remains unclear. Several lines of
      evidence had suggested that the TSHR protease is likely a member of the a
      disintegrin and metalloprotease (ADAM) family of metalloproteases. We show here
      that the expression of ADAM10 was specific to the thyroid by specially designed
      DNA microarrays. We also show that TSH increases TSHR cleavage in a dose
      dependent manner. To prove that ADAM10 is indeed the TSHR cleavage enzyme, we
      investigated the effect of TSH-induced cleavage by a peptide based on a motif
      (TSHR residues 334-349), shared with known ADAM10 substrates. TSH increased dose
      dependently TSHR ectodomain cleavage in the presence of wild-type peptide but not
      a scrambled control peptide. Interestingly, TSH increased the abundance of non
      cleaved single chain receptor, as well higher molecular forms of the A-subunit,
      despite their enhancement of the appearance of the fully digested A-subunit. This
      TSH-related increase in TSHR digested forms was further increased by wild-type
      peptide. We have identified for the first time ADAM10 as the TSHR cleavage enzyme
      and shown that TSH regulates its activation.

PMID- 18074396
TI  - Survey of the year 2006 commercial optical biosensor literature.
AB  - We identified 1219 articles published in 2006 that described work performed using
      commercial optical biosensor platforms. It is interesting to witness how the
      biosensor market is maturing with an increased number of instrument manufacturers
      offering a wider variety of platforms. However, it is clear from a review of the
      results presented that the advances in technology are outpacing the skill level
      of the average biosensor user. While we can track a gradual improvement in the
      quality of the published work, we clearly have a long way to go before we
      capitalize on the full potential of biosensor technology. To illustrate what is
      right with the biosensor literature, we highlight the work of 10 groups who have
      their eye on the ball. To help out the rest of us who have the lights on but
      nobody home, we use the literature to address common myths about biosensor
      technology.

PMID- 18074397
TI  - Functional reconstruction and synthetic mimicry of a conformational epitope using
      CLIPS technology.
AB  - This paper describes immunization studies with CLIPS-constrained peptides
      covering only the major part (beta3-loop) of a structurally complex antigenic
      site on human Follicle Stimulating Hormone beta-subunit (FSH-beta). In cases
      where linear and SS-constrained peptides fail, the CLIPS-constrained peptides
      generate polyclonal antibodies with high neutralizing activity for hFSH. The sera
      were shown to be specific for hFSH over human Luteinizing Hormone (hLH) and human
      Chorionic Gonadotropin (hCG). ELISA-competition studies and circular dichroism
      (CD)-measurements illustrate clearly that activity of the peptides in antibody
      binding and generation relates directly to precise and appropriate fixation of
      the peptide conformation. Design of the CLIPS-peptides was entirely based on
      epitope mapping studies with two neutralizing anti-hFSH mAbs. Both mAbs were
      shown to bind to a conformational epitope located at the top of the beta1-beta3
      loop covering the amino acid sequences Y58-P77 (beta3-loop). The results
      described in this paper show that CLIPS-constrained peptides covering the Y58-P77
      sequence provide the minimally required structural entity necessary to generate
      reproducibly sera with high hFSH-neutralizing activity.

PMID- 18074399
TI  - Hydrodynamics-based delivery of plasmid DNA encoding CTLA4-Ig prolonged cardiac
      allograft survival in rats.
AB  - BACKGROUND: Although gene therapy using plasmid vectors is thought to be safer
      compared with viral vectors, poor efficacy of gene transfer is the obstacle
      preventing wide application of plasmid vectors. However, high levels of foreign
      gene expression have been achieved by rapid tail vein injection of a large volume
      of a plasmid DNA solution into rats. Using this technique, we examined the effect
      of rat CTLA4-Ig gene transfer on prevention of cardiac allograft rejection in
      this animal model. METHODS: Recipient Lewis rats were injected with either
      plasmid pCAGGS-CTLA4-Ig-Glu-tag as a treatment vector or plasmid pCAGGS-signal
      peptide (SP)-Ig as a control vector by hydrodynamics-based delivery technique on
      the day before heart transplantation. Hearts from Brown Norway donors were
      transplanted into the neck of Lewis recipients and graft survival was assessed.
      RESULTS: The plasma level of CTLA4-Ig reached a peak of nearly 5 microg/mL 1 day
      after injection, and then slowly decreased but still remained above 0.9 microg/mL
      until 100 days after injection. The recipient rats treated with the control
      vector and untreated rats rejected cardiac allografts within 7 days. On the other
      hand, the median survival time of the grafts treated with pCAGGS-CTLA4Ig-Glu-tag
      was more than 100 days. Histological examination revealed that long-term survival
      allografts contained fewer infiltrating lymphocytes. The serum from recipients
      with long-term survival allograft suppressed allogenic mixed lymphocyte reaction.
      CONCLUSIONS: CTLA4-Ig gene transfer by means of tail vein injection of plasmid
      DNA into a recipient rat resulted in remarkable prolongation of cardiac allograft
      survival with persistent plasma level of CTLA4-Ig protein.

PMID- 18074400
TI  - Efficient targeted transduction of primary human endothelial cells with dual
      targeted lentiviral vectors.
AB  - Angiogenesis is a rate-limiting factor for numerous human diseases. Angiogenic
      vessels and also the endothelium of certain organs such as the lung display
      molecular addresses that can be exploited for the selective delivery of gene
      therapeutics. Lentiviral vectors (LVs) are powerful tools for stable gene
      delivery but their integration and expression in undesired cell types poses a
      serious safety concern. We have developed a dual-targeted LV that can
      specifically target primary endothelial cells (ECs). Cell selectivity is achieved
      during entry, using a modified Sindbis virus envelope, and during transcription,
      with an EC-specific promoter. We evaluated four surface markers for EC targeting
      and seven promoter sequences from genes preferentially expressed in ECs. The
      efficiency and specificity of the double targeted vector were assayed in a panel
      of human primary cultures and tumor cell lines. A vector targeted to CD146, an
      endothelial adhesion molecule, and carrying a derivative of the EC tyrosine
      kinase Tie2 promoter, increased specificity of transduction up to 50 times and
      was also effective at selectively transducing ECs in a mixed coculture with human
      fibroblasts. The vector presented here is a potentially powerful tool that could
      be used in a variety of human diseases.

PMID- 18074401
TI  - Newly-developed Sendai virus vector for retinal gene transfer: reduction of
      innate immune response via deletion of all envelope-related genes.
AB  - BACKGROUND: Recombinant Sendai virus vectors (rSeV) constitute a new class of
      cytoplasmic RNA vectors that have shown efficient gene transfer in various
      organs, including retinal tissue; however, the related immune responses remain to
      be overcome in view of clinical applications. We recently developed a novel rSeV
      from which all envelope-related genes were deleted (rSeV/dFdMdHN) and, in the
      present study, assess host immune responses following retinal gene transfer.
      METHODS: rSeV/dFdMdHN or conventional F-gene deleted rSeV (rSeV/dF) was injected
      into subretinal space of adult Wistar rats or C57BL/6 mice. The transgene
      expression and histopathological findings were assessed at various time points.
      Immunological assessments, including the expression of proinflammatory cytokines,
      natural killer (NK)-cell activity, as well as SeV-specific cytotoxic T
      lymphocytes (CTLs) and antibodies, were performed following vector injection.
      RESULTS: rSeV/dFdMdHN showed high gene transfer efficiency into the retinal
      pigment epithelium at an equivalent level to that seen with rSeV/dF. In the early
      phase, the upregulation of proinflammatory cytokines, local inflammatory cell
      infiltration and tissue damage that were all prominently seen in rSeV/dF
      injection were dramatically diminished using rSeV/dFdMdHN. NK cell activity was
      also decreased, indicating a reduction of the innate immune response. In the
      later phase, on the other hand, CTL activity and anti-SeV antibodies were
      similarly induced, even using rSeV/dFdMdHN, and resulted in transient transgene
      expression in both vector types. CONCLUSIONS: Deletion of envelope-related genes
      of rSeV dramatically reduces the vector-induced retinal damage and may extend the
      utility for ocular gene transfer; however, further studies regulating the
      acquired immune response are required to achieve long-term transgene expression
      of rSeV.

PMID- 18074402
TI  - Drug-induced readthrough of premature stop codons leads to the stabilization of
      laminin alpha2 chain mRNA in CMD myotubes.
AB  - BACKGROUND: The most common form of congenital muscular dystrophy is caused by a
      deficiency in the alpha2 chain of laminin-211, a protein of the extracellular
      matrix. A wide variety of mutations, including 20 to 30% of nonsense mutations,
      have been identified in the corresponding gene, LAMA2. A promising approach for
      the treatment of genetic disorders due to premature termination codons (PTCs) is
      the use of drugs to force stop codon readthrough. METHODS: Here, we analyzed the
      effects of two compounds on a PTC in the LAMA2 gene that targets the mRNA to
      nonsense-mediated RNA decay, in vitro using a dual reporter assay, as well as ex
      vivo in patient-derived myotubes. RESULTS: We first showed that both gentamicin
      and negamycin promote significant readthrough of this PTC. We then demonstrated
      that the mutant mRNAs were strongly stabilized in patient-derived myotubes after
      administration of negamycin, but not gentamicin. Nevertheless, neither treatment
      allowed re-expression of the laminin alpha2-chain protein, pointing to problems
      that may have arisen at the translational or post-translational levels.
      CONCLUSIONS: Taken together, our results emphasize that achievement of a clinical
      benefit upon treatment with novel readthrough-inducing agents would require
      several favourable conditions including PTC nucleotide context, intrinsic and
      induced stability of mRNA and correct synthesis of a full-length active protein.

PMID- 18074403
TI  - Improved co-oxidation of beta-carotene to beta-ionone using xanthine oxidase
      generated reactive oxygen species in a multiphasic system.
AB  - beta-Ionone, an aroma compound exhibiting flower notes, can be obtained from beta
      carotene in a cooxidation system utilizing xanthine oxidase-generated reactive
      oxygen species (ROS). ROS have to be controlled as, although they can give rise
      to beta-ionone, they may also degrade it. In this work, the biotransformation of
      beta-carotene into beta-ionone was investigated in systems containing variable
      proportions of decane to extract beta-ionone before degradation. The use of 50%
      or 90% decane resulted in increased production yields. Tween 80, which was added
      to further improve the production, slightly decreased the reactivity of the
      medium and the extraction of beta-carotene, but increased the extraction of beta
      ionone. In total, the addition of Tween 80 significantly improved the yields of
      conversion, which reached 34% with 50% decane and 2.5 g/L Tween 80 compared to
      10% without decane and Tween 80. These results show that it is possible to
      control a ROS-mediated reaction by the addition of a solvent phase and by
      modifing the medium composition.

PMID- 18074404
TI  - Statistical methods for efficiency adjusted real-time PCR quantification.
AB  - The statistical treatment for hypothesis testing using real-time PCR data is a
      challenge for quantification of gene expression. One has to consider two key
      factors in precise statistical analysis of real-time PCR data: a well-defined
      statistical model and the integration of amplification efficiency (AE) into the
      model. Previous publications in real-time PCR data analysis often fall short in
      integrating the AE into the model. Novel, user-friendly, and universal AE
      integrated statistical methods were developed for real-time PCR data analysis
      with four goals. First, we addressed the definition of AE, introduced the concept
      of efficiency-adjusted Delta Delta Ct, and developed a general mathematical
      method for its calculation. Second, we developed several linear combination
      approaches for the estimation of efficiency adjusted Delta Delta Ct and
      statistical significance for hypothesis testing based on different mathematical
      formulae and experimental designs. Statistical methods were also adopted to
      estimate the AE and its equivalence among the samples. A weighted Delta Delta Ct
      method was introduced to analyze the data with multiple internal controls. Third,
      we implemented the linear models with SAS programs and analyzed a set of data for
      each model. In order to allow other researchers to use and compare different
      approaches, SAS programs are included in the Supporting Information. Fourth, the
      results from analysis of different statistical models were compared and
      discussed. Our results underline the differences between the efficiency adjusted
      Delta Delta Ct methods and previously published methods, thereby better
      identifying and controlling the source of errors introduced by real-time PCR data
      analysis.

PMID- 18074405
TI  - Assessing horizontal equity in medication treatment among elderly Mexicans: which
      socioeconomic determinants matter most?
AB  - Many low- and middle-income countries are currently undergoing a dramatic
      epidemiological transition, with an increasing disease burden due to degenerative
      noncommunicable diseases. Inexpensive medication treatment often represents a
      cost-effective means to prevent, control or cure many of these health conditions.
      Using micro-data from the 2001 Mexican Health and Aging Study, we assess
      horizontal inequity in medication treatment among older Mexicans before the
      introduction of Popular Health Insurance in Mexico. In doing so, we investigate
      the role of various dimensions of socioeconomic status for obtaining indicated
      medication treatment within a comparatively fragmented health-care system that
      features relatively high out-of-pocket expenditures. Our empirical analysis
      suggests health insurance coverage as a key socioeconomic determinant of
      indicated medication use with large and statistically significant positive
      effects on take-up. The effects of insurance status thereby clearly dominate any
      other possible effects of socioeconomic status on medication treatment. Our
      results thus highlight the importance of access to reliable health care and
      comprehensive coverage for rational medication use in the management of
      degenerative diseases. In light of this evidence, we expect that recent Mexican
      health-care reforms, which expand health insurance coverage to the previously
      uninsured population, will alleviate socioeconomic gradients in medication
      treatment among older people in need.

PMID- 18074406
TI  - Impact of breast cancer diagnosis and treatment on women's sexuality: a survey of
      Japanese patients.
AB  - OBJECTIVE: Research on the impact of breast cancer on Asian women's sexual lives
      is extremely scarce. This study investigated the sexual changes experienced by
      breast cancer patients in Japan following surgery, and their sexuality-related
      information needs. METHODS: An anonymous, cross-sectional survey of breast cancer
      out-patients was conducted in 2005. Data from 85 subjects, who were without
      recurrence and reported being sexually active pre-surgery, were analyzed.
      RESULTS: Subjects were mainly in their 40's and 50's, and the median time since
      surgery was 43 months. Seventy-three (85.9%) had resumed sex after surgery with
      the median time being 3.5 months after surgery. Among 73 who resumed sex, 43
      reported that the frequency of sex decreased, and 72 reported at least one
      sexually related change. The multiple logistic regression analysis revealed that
      those who had perceived the sexual relationship with their partner important
      before surgery (OR, 6.705; 95%CI, 1.320-34.051; p = 0.022) were more likely to
      maintain the same frequency of sex as before surgery. Perceived changes in
      respondents' sexual relationship did not necessarily result in deterioration of
      the couple's overall relationship. Regarding sexuality-related information needs,
      respondents wished to have information on treatment-induced sexual changes as
      well as sexual and general inter-couple communication strategies. CONCLUSION:
      This research revealed that breast cancer patients in Japan experience various
      sexual problems following breast cancer treatment. Sexuality-related information
      should be provided to all patients, regardless of patients age or type of
      surgery, as a part of routine treatment information giving.

PMID- 18074407
TI  - Incorporating feelings related to the uncertainty about future health in utility
      measurement.
AB  - The cost-effectiveness of health-care interventions is often evaluated using
      quality-adjusted life years (QALYs) as a measure of outcome. QALYs are valid
      representations of welfare only under the questionable assumption of additive
      independence of utility of health states across time periods. Therefore, some
      alternatives to QALYs have been proposed, among them healthy-year equivalents
      (HYEs) (Med. Decis. Making 1989; 9(2):142-149) and a semi-separable utility
      function (SSUF) (J. Health Econ. 2005; 24(1):33-54). This paper shows that HYEs
      using a single probability-equivalent standard gamble (SG) question measure the
      same health construct as the SSUF, which uses a series of probability-equivalent
      SG questions. The underlying assumption is that final health states are
      independent of initial health states. In contrast to the SSUF, however, HYEs are
      not bound by this assumption and also avoid propagating bias in the measurement
      of SG utilities from one question to the next. This paper also shows that both
      approaches can incorporate feelings related to the uncertainty about future
      health and capture them by using certainty equivalent questions.

PMID- 18074408
TI  - Dyspnea experience and management strategies in patients with lung cancer.
AB  - OBJECTIVE: The aim of this paper was to describe lung cancer patients' experience
      of dyspnea and their strategies for managing the dyspnea. METHODS: Semi
      structured interviews with two main questions about dyspnea experiences and
      management were conducted with 20 patients with lung cancer, not amenable to
      curative treatment, who had completed life prolonging treatments. Data analysis
      was made with a descriptive, qualitative content analysis. RESULTS: The two
      questions resulted in two domains with 7 categories and subcategories. The
      experience of dyspnea included four categories: 'Triggering factors' included
      circumstances contributing to dyspnea, which comprised physical, psychosocial and
      environmental triggers. Bodily manifestations were considered to be the core of
      the experience. 'Immediate reactions' concerned physical and psychological
      impact. The long-term reactions included limitations, increased dependence and
      existential impact concerning hope, hopelessness and thoughts of death. The
      experience of managing dyspnea included three categories: 'Bodily strategies',
      'psychological strategies' and 'medical strategies'. CONCLUSION: Dyspnea
      experience is a complex experience which influences the life of the patients both
      with immediate reactions and long-term reactions concerning physical, emotional
      and existential issues in life and patients address this experience with managing
      strategies in order to take control of their situation, although they do not seem
      to be able to meet the existential distress they experience.

PMID- 18074409
TI  - Can we fix it? Yes we can! But what? A new test of procedural invariance in TTO
      measurement.
AB  - The TTO-method is often used to value health states, but it is susceptible to
      several biases and methodological difficulties. One of these is a violation of
      procedural invariance, which means that the way a TTO-question is framed, i.e.
      either by fixing the period in imperfect health or that in perfect health, can
      have a substantial effect on the elicited value of a health state. There are four
      important sources of discrepancy of the two procedures: loss aversion, maximum
      endurable time, scale compatibility and discounting. In this article, we present
      the results of a new test of procedural invariance in which we avoided or
      corrected for two of these sources (discounting and maximum endurable time). Our
      results indicate that while correcting for discounting does diminish the
      difference between the two TTO-procedures, a large and significant violation of
      procedural invariance remains. Loss aversion is probably the main determinant of
      the remainder of this difference.

PMID- 18074410
TI  - Overuse injuries in female athletes.
AB  - The last three decades have witnessed a tremendous increase in female sports
      participation at all levels. However, increased sports participation of female
      athletes has also increased the incidence of sport-related injuries, which can be
      either acute trauma or overuse injuries. Overuse injuries may be defined as an
      imbalance caused by overly intensive training and inadequate recovery, which
      subsequently leads to a breakdown in tissue reparative mechanisms. This article
      will review the most frequent overuse injuries in female athletes in the context
      of anatomical, physiological, and psychological differences between genders.

PMID- 18074411
TI  - Threats to the integrity of the Croatian Medical Journal.

PMID- 18074412
TI  - Is content of medical journals related to advertisements? Case-control study.
AB  - AIM: To assess the relatedness of journal content to paid advertisements
      published in the journal. METHODS: The case-control study was performed on a
      convenience sample of 7 journals subscribed by Central Medical Library in Moscow-
      4 international (American Journal of Hypertension, British Journal of General
      Practice, The Lancet, and New England Journal of Medicine) and 3 Russian peer
      reviewed journals (Terapevticheskii Arkhiv, Khirurgiia, and Voeno-Meditsinskii
      Zhurnal). In each issue containing a paid advertisement, classifieds excluded, we
      searched for articles related to the advertised product and compared this issue
      with a control issue - the next or a later issue without this advertisement.
      RESULTS: In American Journal of Hypertension (33 issues from 2002-2004) 94
      placements of advertisements were found, 7 of which were closely related to the
      article topic in the same issue (7/94) vs 2/66 in the control issue. The odds
      ratio (OR) and 95% confidence interval (CI) for advertisements to be accompanied
      by related articles was OR, 2.6; 95%CI, 0.5-13). In British Journal of General
      Practice (27 issues from 2003-2005) there were 7/63 advertisements related to the
      article topic vs 0/28 in the control issue (OR, 7.2; 95% CI, 1.3 to 44). In The
      Lancet (49 issues from 2004) there were 8/162 advertisements related to the
      article topic vs 8/104 in the control issue (OR, 0.6; 95% CI, 0.3-1.5). In New
      England Journal of Medicine (37 issues from 2004) there were 12/81 advertisements
      related to the article topic vs 8/75 in the control issue (OR, 1.5; 95% CI, 0.56
      3.79). In Terapevticheskii Arkhiv (10 issues from 2004) there were 38/93
      advertisements related to the article topic vs 1/83 in the control issue (OR,
      56.66; 95% CI, 4.4-253). In Khirurgiia (25 issues from 2003-2005) there were 3/83
      advertisements related to the article topic vs 0/70 in the control issue (OR,
      2.7; 95% CI, 0.3-26). In Voeno-Meditsinskii Zhurnal (33 issues from 2003-2005)
      there were 17/31 advertisements related to the article topic vs 2/31 in the
      control issue (OR,17.6; 95% CI, 3.6-87). CONCLUSIONS: The strong relatedness
      between the content of the articles and advertisements placed in 3 of 7 journals
      and explicit placement of the advertisements face to face or overleaf the related
      research articles support the hypothesis that journal content is manipulated to
      place more emphasis on the advertisements.

PMID- 18074413
TI  - Effect of rosiglitazone and metformin on insulin resistance in patients infected
      with human immunodeficiency virus receiving highly active antiretroviral therapy
      containing protease inhibitor: randomized prospective controlled clinical trial.
AB  - AIM: To evaluate and compare effects of 48-week treatment with rosiglitazone and
      metformin on insulin resistance in patients infected with Human Immunodeficiency
      Virus (HIV) receiving highly active antiretroviral therapy (HAART), containing a
      protease inhibitor. METHODS: Randomized prospective controlled clinical trial
      enrolled 90 male patients infected with HIV and having impaired glucose tolerance
      and insulin resistance (fasting insulin concentration >20 mIU/L). The patients
      were randomly assigned into three groups; the first group receiving 4 mg
      rosiglitazone once a day, the second group receiving 500 mg metformin two times a
      day, and the third group serving as control without hypoglycemic treatment. The
      primary efficacy parameters were fasting plasma glucose and insulin levels
      compared between baseline and week. Data on insulin resistance and beta cell
      function were analyzed by the Homeostasis Model Assessment (HOMA). RESULTS: After
      48 weeks of treatment, the fasting insulin concentration (+/-standard deviation)
      in rosiglitazone group significantly declined from 39.0+/-3.35 to 19.7+/-3.99
      mIU/L (P<0.001; 49% decrease) and in metformin group from 40.3+/-2.29 to 29.2+/
      2.82 mIU/L (P<0.001; 27% decrease). HOMA indicated that rosiglitazone
      significantly reduced insulin resistance from 11.3+/-1.03 to 4.0+/-0.95
      (P<0.001), compared with metformin which reduced it from 11.9+/-0.73 to 5.7+/
      0.62 (P<0.001). Insulin resistance was significantly lower in the rosiglitazone
      group after 48 weeks (P<0.001). Metformin significantly improved beta cell
      function (from 257.3+/-21.91 to 707.4+/-207.32; P<0.001), as did rosiglitazone as
      well (from 261.3+/-27.98 to 403.3+/-162.50; P<0.001), but the improvement in the
      metformin group was significantly better (P<0.001). However, metformin was more
      efficient in improving beta cell function (from 257.3+/-21.91 to 707.4+/-207.32)
      than rosiglitazone (from 261.3+/-27.98 to 403.3+/-162.50). CONCLUSIONS: Both
      rosiglitazone and metformin were effective and well tolerated in HIV treated with
      protease inhibitor-containing HAART. Rosiglitazone significantly more reduced
      insulin resistance, while beta cell function was significantly better in patients
      on metformin. Both drugs may be considered as an appropriate therapy, with
      rosiglitazone being a better alternative in treating insulin resistance in this
      patient population. ClinicalTrials.gov trial registration number: NCT00483392.

PMID- 18074414
TI  - Polymorphisms of killer cell immunoglobulin-like receptor gene: possible
      association with susceptibility to or clearance of hepatitis B virus infection in
      Chinese Han population.
AB  - AIM: To explore whether killer cell immunoglobulin-like receptors (KIR) gene
      polymorphisms are associated with susceptibility to persistent hepatitis B virus
      (HBV) infection or HBV clearance. METHODS: Fifteen known KIR genes were
      determined in 150 chronic hepatitis B patients, 251 spontaneously recovered
      controls, and 412 healthy controls by the sequence specific primer polymerase
      chain reaction (SSP-PCR) method. KIR genotype frequency (gf) differences were
      tested for significance by two-tailed Fisher exact test or chi(2) test.
      Multifactorial analysis was also performed by logistic analysis (the SAS system).
      RESULTS: Framework genes KIR2DL4, KIR3DL2, KIR3DL3, and KIRZ were present in all
      individuals. The frequencies of KIR2DS2 and KIR2DS3 were higher in chronic
      hepatitis B patients, than in both healthy and spontaneously recovered controls.
      The frequencies of activating KIR2DS1, KIR3DS1, and the inhibitory KIR2DL5 were
      higher in spontaneously recovered controls than in chronic hepatitis B patients
      and healthy controls. CONCLUSION: KIR polymorphisms may be associated with
      susceptibility to HBV infection or HBV clearance. It could be suggested that
      KIR2DS2 and KIR2DS3 were HBV-susceptive genes, which induced a persistent yet
      weak inflammatory reaction that resulted in continuous injury of live tissues and
      chronic hepatitis. KIR2DS1, KIR3DS1, and KIR2DL5, on the other hand, may be
      protective genes that facilitated the clearance of HBV.

PMID- 18074415
TI  - Hla-Cw7 allele as predictor of favorable therapeutic response to interferon-alpha
      in patients with chronic hepatitis C.
AB  - AIM: To evaluate the association between human leukocyte antigens (HLA) class I
      and therapeutic response to interferon-alpha in Croatian patients with chronic
      hepatitis C. METHODS: HLA-A, -B, and -C genotyping was performed in 55 patients
      with sustained virological response and in 57 patients without sustained
      virological response to interferon-alpha therapy. Patients were treated in the
      period from 1998-2001 with interferon-alpha at a dose of 3 million units three
      times a week. Patients who became negative for hepatitis C virus RNA after 12
      weeks of therapy completed 48 weeks of therapy. RESULTS: There was no association
      between therapeutic outcome and frequency of HLA-A, as well as of HLA-B alleles.
      HLA-Cw7 was significantly more frequent in patients with than those without
      sustained virological response (27.0% vs 6.7%; P=0.011). CONCLUSION: In Croatian
      patients with chronic hepatitis C, HLA-Cw7 is the predictor of sustained
      virological response to interferon-alpha therapy.

PMID- 18074416
TI  - Quality of life outcome of critical care survivors eighteen months after
      discharge from intensive care.
AB  - AIM: To assess the changes in health-related quality of life in patients
      discharged from the intensive care unit (ICU). METHODS: At the General University
      ICU, Trauma Hospital in Athens, 242 patients were enrolled prospectively over a
      study period of 18 months. Out of these, 116 participants (47.9%) completed all
      survey components at 6, 12, and 18 months. We used Quality of Life-Spanish (QOL
      SP) to assess the health-related quality of life. Patients or their relatives
      were interviewed on ICU admission and at 6, 12, and 18 months after discharge
      from the ICU. RESULTS: Mean quality of life score of the patients increased from
      2.9+/-4.8 (out of maximum 25 points) on ICU admission to 7.0+/-7.2 points at 6
      months after discharge, and then decreased to 5.6+/-6.9 points at 18 months
      (P<0.001; Friedman Test). Multilinear regression analysis showed that the
      variables which had the strongest association with the quality of life on
      admission were age (P=0.002) and male sex (P=0.001), whereas age (P<0.001),
      length of ICU stay (P<0.001), and male sex (P=0.002) had the strongest
      association 18 months after discharge from the ICU. Survival rate was 66.9% at
      discharge from ICU and 61.6% at hospital discharge. There were 33% deaths in the
      ICU, 5.3% in the hospital, and 6.2% after ICU discharge. There were 7.4% patients
      lost to follow-up. CONCLUSIONS: After discharge from the ICU, patients' quality
      of life was poor and showed an improvement at 18 months after discharge, but was
      still worse than on admission. Age, ICU length of stay, and male sex were the
      factors that had the strongest impact on the quality of life on admission and at
      18 months after discharge from the ICU.

PMID- 18074417
TI  - Assessment of Crohn's disease activity by doppler ultrasound of superior
      mesenteric artery and mural arteries in thickened bowel wall: cross-sectional
      study.
AB  - AIM: To define sensitive and reliable Doppler parameters for measurements in the
      superior mesenteric artery and mural arteries of affected bowel loops used in the
      assessment of Crohn disease activity. METHODS: We performed cross-sectional study
      at a tertiary care setting in Zagreb, Croatia, between January 2001 and March
      2005. We measured arterial flow in the superior mesenteric artery and affected
      bowel wall in 138 patients with Crohn disease (74 with active, 64 with inactive
      disease) and 67 healthy volunteers. The disease activity was determined by the
      clinical examination, Crohn disease activity index, and standard laboratory
      tests. Superior mesenteric artery color and pulsed Doppler parameters were peak
      systolic velocity, end-diastolic velocity, resistance index, mean velocity flow,
      cross-sectional area, and flow volume. When gut mural vessels were identified, we
      performed spectral analysis of mural arteries by pulsed Doppler, with a
      measurement of resistance index. RESULTS: The measurements in the superior
      mesenteric artery showed statistically and clinically significant difference in
      flow volume in active group, compared with inactive and control groups (C+/
      Q=564+/-263 mL/min for active, 421+/-157 for inactive and 416+/-248 for control
      group). Affected bowel loops analysis showed significant difference between
      inactive and active Crohn disease group in wall thickness (3.1+/-1.4 vs 5.0+/-1.8
      mm, P<0.001, Mann-Whitney test) while all participants from control group had
      thickness below 2mm. Intensity of color Doppler signals was different for all
      groups (P<0.001, chi(2) test) with the highest level of hyperemia in the active
      group. Resistance index measurements of mural arteries in bowel wall revealed
      differences between all three groups (0.61+/-0.05 in active group, 0.71+/-0.05 in
      the inactive group and 0.80+/-0.11 in the control group, P<0.001, Kruskal-Wallis
      test). CONCLUSION: Intensity of color Doppler signals and resistance index
      measurements of mural arteries in the thickened bowel wall can be used as
      quantitative diagnostic tool in the assessment of Crohn disease activity.

PMID- 18074418
TI  - Management of diabetes in pregnancy: comparison of guidelines with current
      practice at Austrian and Australian obstetric center.
AB  - AIM: To compare Austrian and Australian national guidelines for gestational and
      pre-gestational diabetes and estimate the level to which physicians comply with
      their country's guidelines. METHODS: Austrian (ODG, Austrian Diabetes Society)
      and Australian guidelines (ADIPS, Australasian Diabetes in Pregnancy Society) for
      the treatment of gestational diabetes and pre-gestational diabetes were
      systematically reviewed. Current practices in two obstetric centers in Austria
      and Australia were assessed by interviewing key stakeholders through
      questionnaires assessing different components of diabetes care. For gestational
      diabetes, these components were screening, abnormal oral glucose tolerance test
      values (mmol/L), abnormal values for diagnosis, further management when abnormal
      values are detected, monitoring/glucose targets (mmol/L), further management and
      indications for insulin therapy, route and timing of delivery, and postpartum
      management and counseling. For pre-gestational diabetes, the components were
      management during the preconceptional period, glucose target values, medical
      surveillance, obstetric surveillance, medication used, route and timing of
      delivery, and postpartum management and counseling. RESULTS: More variation was
      found in the management of gestational than pre-gestational diabetes. There were
      differences in oral glucose tolerance test and cut-off levels for diagnosing
      gestational diabetes in both centers and guidelines. Australian guidelines
      recommended two-stage screening for gestational diabetes, while Austrian
      guidelines recommended one-stage screening. At the Austrian obstetric center,
      amniocentesis was recommended for determining the start of insulin treatment in
      pregnant women with gestational diabetes. This approach was neither used at the
      Australian obstetric center nor recommended by any of the two guidelines.
      CONCLUSION: Our study showed that it was difficult to standardize screening
      criteria and diagnostic methods for gestational and pre-gestational diabetes.
      National and international consensus has yet to be achieved in the management of
      diabetes in pregnancy.

PMID- 18074419
TI  - Role of poultry meat in sporadic Campylobacter infections in Bosnia and
      Herzegovina: laboratory-based study.
AB  - AIM: To investigate genetic diversity and specificity of Campylobacter jejuni and
      Campylobacter coli strains isolated from humans, retail poultry meat, and live
      farm chickens in Zenica-Doboj Canton, Bosnia and Herzegovina, and identify the
      role of poultry meat in sporadic Campylobacter infections. METHODS: We determined
      the type of Campylobacter species using standard microbiological methods and
      multiplex polymerase chain reaction (PCR), and performed pulsed field gel
      electrophoresis (PFGE) and restriction fragment length polymorphism (RFLP) typing
      of the flaA gene to investigate genetic diversity among the isolates. RESULTS: We
      isolated C jejuni and C coli from 75 (5.2%) of 1453 samples of consecutive
      outpatients with sporadic diarrhea; from 51 (34.7%) of 147 samples of poultry
      meat; and from 15 out of 23 farm chicken samples. The proportion of C coli found
      among human (30.1%), poultry meat (56.9%), and farm chicken isolates (53.3%), was
      greater than the proportion of C jejuni. Fourteen and 24 PFGE genotypes were
      identified among 20 C coli and 37 C jejuni isolates, respectively. Identical PFGE
      genotypes were found in two cases of human and poultry meat isolates and two
      cases of poultry meat and farm chicken isolates. CONCLUSION: Only a minority of
      human Campylobacter isolates shared identical PFGE type with poultry meat
      isolates. Although poultry is the source of a certain number of human infections,
      there may be other more important sources. Further research is required to
      identify the environmental reservoir of Campylobacter spp responsible for causing
      human disease and the reason for the high prevalence of C coli human infections
      in this region.

PMID- 18074420
TI  - Preschool children as frequent attenders in primary health care in Croatia:
      retrospective study.
AB  - AIM: To define predictive factors for frequent attenders among preschool children
      in primary health care and investigate the association between socioeconomic
      factors and medical factors, as well as the reasons for child's appointment in
      the physician's office. METHODS: This retrospective study was conducted in 7
      primary health care offices (6 family physician practices and 1 pediatric
      practice) in Zagreb, Croatia. The study included 964 preschool children from 1-6
      years who visited these practices during 2005. Children in the highest quartile
      of consultation frequency (n=255) were defined as frequent attenders, while the
      children in the lowest quartile of consultation frequency (n=302) represented the
      control group (non-frequent attenders). We collected data on consultation rate,
      socioeconomic factors, health care providers, prescriptions and referrals,
      symptoms, and diagnoses. Association of the parameters and the frequency of
      consultations was investigated by logistic regression analysis. RESULTS: Frequent
      attenders sought for consultations 10 times per year (median, range 4-26), and
      they had the following characteristics: had 2-3 years, attended day care center,
      were treated by a pediatrician, and received more prescriptions and referrals.
      Their major complaints were: cough, nasal discharge, rash, fever, difficult
      breathing, earache, digestive problems, throat soreness, and injuries. Logistic
      regression analysis showed significant association between frequent attendance
      and age of 2-3, the symptom of nasal discharge, and diagnoses of infectious and
      parasitic diseases, middle ear diseases, respiratory system diseases, and skin
      and subcutaneous tissue diseases. CONCLUSION: Socioeconomic characteristics,
      symptoms, and diagnoses were important predictors for defining preschool frequent
      attenders in primary health care.

PMID- 18074421
TI  - Diffuse lymphomatous infiltration of kidney presenting as renal tubular acidosis
      and hypokalemic paralysis: case report.
AB  - We report the case of a 22-year-old woman who presented with acute onset flaccid
      quadriparesis. Physical examination showed mild pallor with cervical and axillary
      lymphadenopathy, hepatomegaly, and bilateral smooth enlarged kidneys.
      Neurological examination revealed lower motor neuron muscle weakness in all the
      four limbs with hyporeflexia and normal sensory examination. Laboratory
      investigations showed anemia, severe hypokalemia, and metabolic acidosis.
      Urinalysis showed a specific gravity of 1.010, pH of 7.0, with a positive urine
      anion gap. Ultrasound revealed hepatosplenomegaly with bilateral enlarged smooth
      kidneys. Renal biopsy was consistent with the diagnosis of non-Hodgkin lymphoma
      (B cell type). Metabolic acidosis, alkaline urine, and severe hypokalemia due to
      excessive urinary loss in our patient were suggestive of distal renal tubular
      acidosis. Renal involvement in lymphoma is usually subclinical and clinically
      overt renal disease is rare. Diffuse lymphomatous infiltration of the kidneys may
      cause tubular dysfunction and present with hypokalemic paralysis.

PMID- 18074422
TI  - Decreased androgen levels and improved menstrual pattern after angiotensin II
      receptor antagonist telmisartan treatment in four hypertensive patients with
      polycystic ovary syndrome: case series.
AB  - We describe 4 consecutive hypertensive women with polycystic ovary syndrome,
      classified according to the National Institute of Child Health and Human
      Development (NICHD) criteria, treated with telmisartan 40 mg/d for six months.
      Blood pressure, menstrual pattern, body mass index (BMI), homeostasis model
      assessment of insulin resistance, testosterone, dehydroepiandrosterone sulfate
      (DHEAS), and androstenedione were recorded and measured before and after
      telmisartan treatment. Obese hypertensive polycystic ovary syndrome patients had
      a decrease in systolic blood pressure. Marked drop-off in serum androgen
      concentrations was observed in all four patients. Three patients improved their
      menstrual cyclicity. The improvements were independent of changes in weight. The
      reduction of androgen concentrations and improvement in menstrual pattern was
      achieved despite a non-significant change of fasting insulin levels in patients,
      who were not considered severely insulin resistant at baseline. These findings
      may provide a new basis for a proper choice of the antihypertensive drug in
      hypertensive women with polycystic ovary syndrome.

PMID- 18074423
TI  - Abbreviated clinical study reports with investigational medicinal products for
      human use: current guidelines and recommendations.

PMID- 18074424
TI  - Recommending disorder in health care systems.

PMID- 18074425
TI  - Mortality patterns among adult women in Malawi, 1979-2004.

PMID- 18074426
TI  - Where to go for your winter vacation.

PMID- 18074427
TI  - 47th ICAAC--Chicago conference update.

PMID- 18074428
TI  - Complications in HIV treatment. TB and co-infection news from IAS.

PMID- 18074429
TI  - Update on new antiretroviral drugs. An interview with Harold Kessler, M.D. by
      Matt Sharp.

PMID- 18074430
TI  - Point-of-care HIV testing using rapid HIV test kits: guidance for health-care
      professionals.

PMID- 18074431
TI  - Quality of life after liver transplantation for acute hepatic failure.
AB  - Liver transplantation is now an accepted and successful therapy for both acute
      and cronic liver diseases. Whilst the study of health related quality of life
      (HRQoL) post-transplantation for chronic liver disease (CLD) has been well
      documented, there is little data measuring HRQoL following liver transplantation
      for acute liver failure (ALF), despite super urgent transplantation constituting
      16.6% of al United Kingdom liver transplantation. Therefore, the aim of the
      present study was to document the HRQoL in patients who have received an
      emergency liver transplant for ALF. Data collection employed between method
      triangulation, using the Short Form 36 quality of life health questionnaire for
      both ALF (n=47) and CLD (n=49), and six semi-structured interviews. Only the
      qualitative element of the study is reported here. Phenomenological analysis of
      the semi-structured interviews identified four themes relating to the physical
      changes encountered (inactivity), physical recovery (health transition); changes
      made to the transplant recipients life styles (modification); and outlook. The
      majority of transplanted ALF transplant recipients' stated that they have a good
      quality of life, which was often comparable to their pretransplantation
      lifestyle. However, the initial recovery process was often difficult and was
      related to the physical changes instigated from their multi-organ failure and
      intensive care stay, which can present numerous physical and emotional
      challenges.

PMID- 18074432
TI  - Editorial comment on: Thermotherapy of prostate cancer using magnetic
      nanoparticles: feasibility, imaging, and three-dimensional temperature
      distribution.

PMID- 18074433
TI  - 2007 Guideline for the management of ureteral calculi.

PMID- 18074434
TI  - The US President's Malaria Initiative: 2 years on.

PMID- 18074435
TI  - Africa counts greater successes against malaria.

PMID- 18074436
TI  - Editorial comment on: Prospective evaluation of quality of life in prostate
      cancer patients receiving combined treatment of postoperative radiotherapy plus
      androgen suppression for PT3 or positive resection margin after radical
      prostatectomy.

PMID- 18074437
TI  - Editorial comment on: Prospective evaluation of quality of life in prostate
      cancer patients receiving combined treatment of postoperative radiotherapy plus
      androgen suppression for PT3 or positive resection margin after radical
      prostatectomy.

PMID- 18074438
TI  - Words of wisdom. Re: Efficacy of botulinum toxin-A for treating idiopathic
      detrusor overactivity: results from a single center, randomized, double-blind,
      placebo controlled trial.

PMID- 18074439
TI  - Words of wisdom. Re: Burch colposuspension versus fascial sling to reduce urinary
      stress incontinence.

PMID- 18074440
TI  - Words of wisdom. Re: High-dose chemotherapy and stem-cell rescue for metastatic
      germ-cell tumors.

PMID- 18074441
TI  - Words of wisdom. Re: The relationship between the extent of surgical margin
      positivity and prostate-specific antigen recurrence in radical prostatectomy
      specimens.

PMID- 18074442
TI  - Words of wisdom. Re: Lymphatic invasion is a prognostic factor for bladder cancer
      treated with radical cystectomy.

PMID- 18074443
TI  - Words of wisdom. Re: radical cystectomy with extended lymphadenectomy: evaluating
      separate package versus en bloc submission for node positive bladder cases.

PMID- 18074444
TI  - In-vitro experimental models for the risk assessment of antibiotic-induced QT
      prolongation.
AB  - The prolongation of the ventricular repolarization and proarrhythmic effects
      (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in
      vitro models. 1. Using the patch clamp technique on the human ether-a-gogo
      related gene (HERG) current, the rank order for blockade of the HERG-current
      (IC(50)) was: sparfloxacin (44 microM)>telithromycin=moxifloxacin=erythromycin
      (+/-100 microM). 2. Assessing their effects on action potential duration
      (APD(90)) and incidence of early afterdepolarizations in isolated rabbit Purkinje
      fibers, the rank order was: sparfloxacin>moxifloxacin>telithromycin>erythromycin
      (prolongation of APD(90) at 100 microM: 83%, 48%, 33% and 17% from baseline
      compared to +5% with solvent, P<0.05, respectively). 3. Assessing the drug
      effects on the APD(60), triangulation, reverse use-dependency, and instability in
      isolated Langendorff-perfused rabbit hearts, the rank order was:
      moxifloxacin>erythromycin>sparfloxacin>telithromycin. 4. Assessing their
      torsadogenic potentials (scores of effects on QT-interval, peak of the T wave to
      end of T wave: T(p-e), T(p-e)/QT ratio, R wave on T wave (R on T) and TdP in
      isolated rabbit left ventricular wedge preparations, the rank order for their TdP
      risk score was: sparfloxacin>erythromycin>moxifloxacin>telithromycin. Additional
      experiments with grepafloxacin indicate that the rank order to detect
      grepafloxacin-induced long QT was the wedge preparation>the Purkinje
      fiber>HERG>the isolated heart, where the isolated heart was unable to detect
      grepafloxacin-induced APD prolongation. The present study demonstrates that the
      first three in-vitro models can be used to assess the ability of antibiotic
      compounds to delay ventricular repolarization. However, with respect to their
      known clinical effects on QT and TdP incidence, the wedge preparation appears to
      be more predictive and suitable for detecting torsadogenic action of antibiotics.

PMID- 18074445
TI  - Knowledge Translation in Emergency Medicine: Establishing a Research Agenda and
      Guide Map for Evidence Uptake. Proceedings of the 2007 Academic Emergency
      Medicine Consensus Conference, May 15, 2007. Chicago, Illinois, USA.

PMID- 18074446
TI  - [Idiopathic thrombocytopenic purpura].

PMID- 18074447
TI  - ["Split Personality": appropriate descriptions of complex symptoms].

PMID- 18074448
TI  - Latex allergy--update.

PMID- 18074449
TI  - Dental nurses: valued members of the team?

PMID- 18074450
TI  - Gigamemorable mnemotechny.

PMID- 18074451
TI  - [Osteoarthritis, rheumatoid arthritis, metabolic disease? Overview of arthralgia
      of unknown origin].

PMID- 18074452
TI  - [Infection, adverse drug effect, metabolic disorder or psychological disorder?
      Help, the mouth burns!].

PMID- 18074453
TI  - [Pathologic worry].
AB  - "Pathologic worry" is a new term in the ICD-10 and DSM-IV-classification of
      anxiety disorders. Worry is a common symptom in psychiatric disorders, special in
      depression and specific for GAD. The new scales DANDTE (self-Rating-Inventory)
      and BOEAS (observer Rating Scale) were developed for the clinical routine and
      provide an economic and precise rating also for other anxiety symptoms. In the
      pharmacotherapy SSRI and SNRI are the first line, but also Buspiron, Opipramol
      and Pregabalin are possible agents in the short-term and long-term therapy.
      Cognitive behaviour therapy is a proofed psychotherapeutic alternative approach.

PMID- 18074454
TI  - [Quality management exemplified by diabetes. How thorough are you already?].

PMID- 18074455
TI  - [Classic drug in diabetes therapy. Revise contraindications?].

PMID- 18074456
TI  - [Interview with congress president Prof. Dr. med. Peter Nawroth, Heidelberg.
      Farewell to glucose centered world view (interview by Jochen Aumiller)].

PMID- 18074457
TI  - [Spontaneous deep venous thrombosis. First symptom of a neoplasm?].

PMID- 18074459
TI  - Abstracts of the 18th International Conference on Oral and Maxillofacial Surgery,
      14-18 November 2007, Bangalore, India.

PMID- 18074458
TI  - The National Service Framework--suggestions about priorities for policy
      development welcome.

PMID- 18074460
TI  - The private sector response to AIDS in Botswana.

PMID- 18074462
TI  - Abstracts of the 20th European College of Neuropsychopharmacology (ECNP)
      Congress, 13-17 October 2007, Vienna, Austria.

PMID- 18074461
TI  - Oligopeptidase B from Leishmania amazonensis: molecular cloning, gene expression
      analysis and molecular model.
AB  - Serine oligopeptidases of trypanosomatids are emerging as important virulence
      factors and therapeutic targets in trypanosome infections. A complete open
      reading frame of oligopeptidase B from Leishmania amazonensis was amplified with
      polymerase chain reaction with gradient annealing temperatures using primers
      designed for the oligopeptidase B gene from L. major. The 2,196-bp fragment coded
      for a protein of 731 amino acids with a predicted molecular mass of 83.49 KDa.
      The encoded protein (La_OpB) shares a 90% identity with oligopeptidases of L.
      major and L. infantum, 84% with L. braziliensis, and approximately 62% identity
      with Trypanosoma peptidases. The oligopeptidase B gene is expressed in all cycle
      stages of L. amazonensis. The three dimensional model of La_OpB was obtained by
      homology modeling based on the structure of prolyl oligopeptidases. We mapped a
      La_OpB model that presents a greater negative charge than prolyl oligopeptidases;
      our results suggest a difference in the S2 subsite when compared to
      oligopeptidases B from Trypanosoma and bacterial oligopeptidases B. The La_OpB
      model serves as a starting point for its exploration as a potential target source
      for a rational chemotherapy.

PMID- 18074463
TI  - Abstracts of the 14th Annual Meeting of the Society for Free Radical Biology and
      Medicine (SFRBM), November 14-18, 2007, Washington, DC, USA.

PMID- 18074464
TI  - Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic
      shock.
AB  - OBJECTIVE: There is ongoing debate about the efficacy of polyvalent
      immunoglobulins as adjunctive therapy for sepsis or septic shock. Two meta
      analyses by the Cochrane collaboration calculated a significant reduction in
      mortality. However, data of the largest study were missing in one, and a subset
      of four high-quality studies failed to show an effect in the other. To broaden
      the database, we performed a meta-analysis of all randomized controlled studies
      published so far. DATA SOURCE: MEDLINE, EMBASE, Cochrane Library of randomized
      trials, and personal files. STUDY SELECTION: Meta-analysis of all published
      randomized controlled studies published on polyvalent immunoglobulins (Ig) for
      treatment of sepsis or septic shock in adults, children, or neonates. DATA
      EXTRACTION: Twenty-seven trials with a total of 2,202 patients fulfilled the
      inclusion criteria. DATA SYNTHESIS: As the immunologic state of neonates is
      different than that of adults or older children, data were evaluated separately
      for each group. Fifteen trials on 1,492 adults could be included. The pooled
      effect on mortality was a relative risk of death (RR) of 0.79 (95% confidence
      interval [CI] 0.69-0.90, p <or= .0003). There was a strong trend in favor of an
      immunoglobulin preparation enriched with IgA and IgM (IgGAM) (RR = 0.66, 95% CI
      0.51-0.84, p <or= .0009) compared with preparations containing only IgG (RR =
      0.85, 95% CI 0.73-0.99, p <or= .04). In 12 trials on 710 neonates, the pooled
      effect on mortality was 0.56 (95% CI 0.42-0.74, p <or= .0001). There was also a
      positive although less pronounced trend favoring the effect of IgGAM (RR = 0.50,
      95% CI 0.34-0.73, p <or= .0003) compared with IgG (RR = 0.63, 95% CI 0.42-0.96, p
      <or= .03). A sensitivity analysis selecting eight trials in adults and ten in
      neonates of highest methodological quality confirmed these results. CONCLUSIONS:
      Polyvalent immunoglobulins exert a significant effect on mortality in sepsis and
      septic shock, with a trend in favor of IgGAM.

PMID- 18074465
TI  - Polyclonal intravenous immunoglobulin for the treatment of severe sepsis and
      septic shock in critically ill adults: a systematic review and meta-analysis.
AB  - OBJECTIVES: To systematically review the literature to assess whether adjunctive
      therapy with polyclonal intravenous immunoglobulin (ivIg) reduces mortality among
      critically ill adults with severe sepsis and septic shock. DATA SOURCE: MEDLINE,
      EMBASE, and Cochrane Central Register of Controlled Trials databases; the meta
      register of controlled trials; and the Medical Editors Trial Amnesty register.
      STUDY SELECTION: Prospective randomized clinical trials (RCTs) evaluating ivIg
      treatment in critically ill adults with severe sepsis or septic shock were
      included. Two reviewers conducted assessment of suitability for inclusion. DATA
      EXTRACTION: Two authors independently determined the validity of included studies
      and extracted data. DATA SYNTHESIS: The effect of ivIg on all-cause mortality was
      quantified using a fixed-effect meta-analysis. RESULTS: Fourteen RCTs published
      between 1988 and 2006 were included. Most were small, used relatively low doses
      of ivIg, and included predominantly surgical patients with Gram-negative
      infections. There was a significant reduction in mortality associated with use of
      ivIg treatment with a pooled odds ratio of 0.66 (95% confidence interval 0.53
      0.83; p < .0005). In general, a greater treatment effect was seen among studies
      of lower methodological quality, studies using higher doses of ivIg, and studies
      that did not use albumin as a control. There was evidence of between-study
      heterogeneity (chi-square p = .009), and this was at least moderate as measured
      by the I2 value (I2 = 53.8%). When only high-quality studies were pooled, the
      odds ratio for mortality was 0.96 (95% confidence interval 0.71-1.3; p = .78).
      CONCLUSIONS: This meta-analysis demonstrates an overall reduction in mortality
      with the use of ivIg for the adjunctive treatment of severe sepsis and septic
      shock in adults, although significant heterogeneity exists among the included
      trials and this result was not confirmed when only high-quality studies were
      analyzed. These data warrant a well-designed, adequately powered, and
      transparently reported clinical trial.

PMID- 18074466
TI  - [Diagnosis and antibiotherapy for community acquired bacterial urinary infections
      in infants and children. Recommendations].

PMID- 18074468
TI  - [Abstracts of the 3rd Pharmacoepidemiology Seminar, 24-25 May 2007, Paris,
      France].

PMID- 18074467
TI  - Spotlight: Evelyn Regar, MD, PhD. Interview by Mark Nicholls.

PMID- 18074469
TI  - Long-term follow-up in cardiac surgery. Interview by James Butcher.

PMID- 18074470
TI  - [Diagnosis and antibiotherapy for community acquired bacterial urinary infections
      in infants and children].

PMID- 18074471
TI  - Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study.
AB  - OBJECTIVE: Intravenous immunoglobulin as an adjunctive treatment in sepsis was
      regarded as promising by a Cochrane meta-analysis of smaller trials. In this
      phase III multicenter trial, we assessed whether intravenous immunoglobulin G
      (ivIgG) reduced 28-day mortality and improved morbidity in patients with score
      defined severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled,
      multicenter trial. SETTING: Twenty-three medical and surgical intensive care
      units in university centers and large teaching hospitals. PATIENTS: Patients (n =
      653) with score-defined sepsis (sepsis score 12-27) and score-defined sepsis
      induced severity of disease (Acute Physiology and Chronic Health Evaluation II
      score 20-35). INTERVENTIONS: Patients were assigned to receive either placebo or
      ivIgG (day 0, 0.6 g/kg body weight; day 1, 0.3 g/kg body weight). MEASUREMENTS
      AND MAIN RESULTS: The prospectively defined primary end point was death from any
      cause after 28 days. Prospectively defined secondary end points were 7-day all
      cause mortality, short-term change in morbidity, and pulmonary function at day 4.
      Six hundred fifty-three patients from 23 active centers formed the intention-to
      treat group, 624 patients the per-protocol group (placebo group, n = 303; ivIgG
      group, n = 321). The 28-day mortality rate was 37.3% in the placebo group and
      39.3% in the ivIgG group and thus not significantly different (p = .6695). Seven
      day mortality was not reduced, and 4-day pulmonary function was not improved.
      Drug-related adverse events were rare in both groups. Exploratory findings
      revealed a 3-day shortening of mechanical ventilation in the surviving patients
      and no effect of ivIgG on plasma levels of interleukin-6 and tumor necrosis
      factor receptors I and II. CONCLUSIONS: In patients with score-defined severe
      sepsis, ivIgG with a total dose of 0.9 g/kg body weight does not reduce
      mortality.

PMID- 18074472
TI  - Oxygen consumption of human peripheral blood mononuclear cells in severe human
      sepsis.
AB  - OBJECTIVE: During sepsis, after an initial stimulation immune cells down-regulate
      their functions, leading to a state of immunosuppression. Because the mechanisms
      of such down-regulation are unclear, we investigated the hypothesis of an
      energetic failure of immune cells to participate in immune dysfunction. DESIGN:
      Cohort of septic shock patients to study peripheral blood mononuclear cells
      (PBMCs) biological energy in comparison to healthy volunteer cells. SETTING:
      Critical care unit and laboratory, university hospital. SUBJECTS: Eighteen severe
      sepsis or septic shock patients and 32 healthy volunteers. INTERVENTIONS: Ex vivo
      measurement of oxygen consumption in PBMCs taken from patients. The PBMCs'
      mitochondrial oxidative phosphorylation was investigated using adenosine
      diphosphate stimulation. The plasma factors implication was tested, using healthy
      cells incubated in septic plasma, or septic cells incubated in healthy plasma, at
      different time points of sepsis. The relationship between monocyte human
      leukocyte antigen-DR expression and bioenergetic results was tested. MEASUREMENTS
      AND MAIN RESULTS: Baseline oxygen consumption was higher in septic PBMCs (p <
      .01), with an attenuated response to adenosine diphosphate stimulation (p < .01).
      Oxygen consumption of healthy PBMCs incubated in septic plasma mimicked the
      septic cell response, with amplitude depending on the duration of sepsis (days 0
      28). Septic cells incubated in healthy plasma partially recovered normal
      patterns. Septic plasma incubation increased the fraction of decoupling oxygen
      consumption (p = .021). A relationship between oxygen consumption (baseline or
      adenosine diphosphate stimulated) and human leukocyte antigen-DR expression was
      observed for incubation with plasma sampled at different time points of septic
      shock. CONCLUSION: Energetic failure of PBMCs in sepsis may be a factor
      associated with the modulation of immune response and human leukocyte antigen-DR
      phenotype, partially driven by plasma factors.

PMID- 18074473
TI  - Overture for growth hormone: requiem for interleukin-6?
AB  - BACKGROUND: Music has been used for therapeutic purposes since the beginning of
      cultural history. However, despite numerous descriptions of beneficial effects,
      the precise mechanisms by which music may improve human well-being remain
      unclear. METHODS: We conducted a randomized study in ten critically ill patients
      to identify mechanisms of music-induced relaxation using a special selection of
      slow movements of Mozart's piano sonatas. These sonatas were analyzed for
      compositional elements of relaxation. We measured circulatory variables, brain
      electrical activity, serum levels of stress hormones and cytokines, requirements
      for sedative drugs, and level of sedation before and at the end of a 1-hr
      therapeutic session. RESULTS: Compared with controls, we found that music
      application significantly reduced the amount of sedative drugs needed to achieve
      a comparable degree of sedation. Simultaneously, among those receiving the music
      intervention, plasma concentrations of growth hormone increased, whereas those of
      interleukin-6 and epinephrine decreased. The reduction in systemic stress hormone
      levels was associated with a significantly lower blood pressure and heart rate.
      CONCLUSION: Based on the effects of slow movements of Mozart's piano sonatas, we
      propose a neurohumoral pathway by which music might exert its sedative action.
      This model includes an interaction of the hypothalamic-pituitary axis with the
      adrenal medulla via mediators of the unspecific immune system

PMID- 18074474
TI  - Abdominal X-ray quiz.

PMID- 18074475
TI  - Paresthesia of the left lower limb.

PMID- 18074476
TI  - Patient-initiated device removal in intensive care units: a national prevalence
      study.
AB  - OBJECTIVE: Information is needed about patient-initiated device removal to guide
      quality initiatives addressing regulations aimed at minimizing physical restraint
      use. Research objectives were to determine the prevalence of device removal,
      describe patient contexts, examine unit-level adjusted risk factors, and describe
      consequences. DESIGN: Prospective prevalence. SETTING: Total of 49 adult
      intensive care units (ICUs) from a random sample of 39 hospitals in five states.
      METHODS: Data were collected daily for 49,482 patient-days by trained nurses and
      included unit census, ventilator days, restraint days, and days accounted for by
      men and by elderly. For each device removal episode, data were collected on
      demographic and clinical variables. RESULTS: Patients removed 1,623 devices on
      1,097 occasions: overall rate, 22.1 episodes/1000 patient-days; range, 0-102.4.
      Surgical ICUs had lower rates (16.1 episodes) than general (23.6 episodes) and
      medical (23.4 episodes) ICUs. ICUs with fewer resources had fewer all-type device
      removal relative to ICUs with greater resources (relative risk, 0.76; 95%
      confidence interval, 0.66-0.87) but higher self-extubation rates (relative risk,
      1.27; 95% confidence interval, 1.07-1.52). Men accounted for 57% of the episodes,
      44% were restrained at the time, and 30% had not received any sedation, narcotic,
      or psychotropic drug in the previous 24 hrs. There was no association between
      rates of device removal with restraint rates, proportion of men, or elderly. Self
      extubation rates were inversely associated with ventilator days (rs = -0.31, p =
      .03). Patient harm occurred in 250 (23%) episodes; ten incurred major harm. No
      deaths occurred. Reinsertion rates varied by device: 23.5% of surgical drains to
      88.9% of monitor leads. Additional resources (e.g., radiography) were used in 58%
      of the episodes. CONCLUSION: Device removal by ICU patients is common, resulting
      in harm in one fourth of patients and significant resource expenditure. Further
      examination of patient-, unit-, and practitioner-level variables may help explain
      variation in rates and provide direction for further targeted interventions.

PMID- 18074477
TI  - Use of a validated delirium assessment tool improves the ability of physicians to
      identify delirium in medical intensive care unit patients.
AB  - OBJECTIVE: Although medical intensive care unit nurses at our institution
      routinely use the Intensive Care Delirium Screening Checklist (ICDSC) to identify
      delirium, physicians rely on traditional diagnostic methods. We sought to measure
      the effect of physicians' use of the ICDSC on their ability to detect delirium.
      DESIGN: Before-after study. SETTING: Medical intensive care unit of an academic
      medical center. PATIENTS AND PARTICIPANTS: A total of 25 physicians with >or=1
      month of clinical experience in the medical intensive care unit conducted 300
      delirium assessments in 100 medical intensive care unit patients. MEASUREMENTS
      AND MAIN RESULTS: Physicians sequentially evaluated two patients for delirium
      using whatever diagnostic method preferred. Following standardized education
      regarding ICDSC use, each physician evaluated two different patients for delirium
      using the ICDSC. Each physician assessment was preceded by consecutive, but
      independent, evaluations for delirium by the patient's nurse and then a validated
      judge using the ICDSC. Before (PRE) physician ICDSC use, the validated judge
      identified delirium in five patients; the physicians and nurses identified
      delirium in zero and four of these patients, respectively. The physicians
      incorrectly identified delirium in four additional patients. After (POST)
      physician ICDSC use, the validated judge identified delirium in 11 patients; the
      physicians and nurses identified delirium in eight and ten of these patients,
      respectively. The physicians incorrectly identified delirium in one patient.
      After physician ICDSC use, agreement improved between both the physicians and
      validated judge (PRE kappa = -0.14 [95% confidence interval {CI} = -0.27 to 
      0.02] to POST kappa = 0.67 [95% CI = 0.38 to 0.96]) and physicians and nurses
      (PRE kappa = -0.15 [95% CI = -0.29 to -0.02] to POST kappa = 0.58 [95% CI = 0.25
      to 0.91]). Nurses vs. validated judge agreement was strong in both periods (PRE
      kappa = 0.65 [95% CI = 0.29 to 1.00] and POST kappa = 0.92 [95% CI = 0.76 to
      1.00]). CONCLUSIONS: Use of the ICDSC, along with education supporting its use,
      improves the ability of physicians to detect delirium in the medical intensive
      care unit.

PMID- 18074478
TI  - Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in
      patients with acute lung injury.
AB  - OBJECTIVE: To identify biological and clinical predictors of acute kidney injury
      in subjects with acute lung injury. DESIGN: Secondary data analysis from a
      multicenter, randomized clinical trial. SETTING: Intensive care units in ten
      university medical centers. PATIENTS: A total of 876 patients enrolled in the
      first National Heart, Lung, and Blood Institute Acute Respiratory Distress
      Syndrome Clinical Network trial. INTERVENTIONS: Study subjects were randomized to
      receive a low tidal volume ventilation strategy and pharmacologic therapy with
      ketoconazole or lisofylline in a factorial design. MEASUREMENTS AND MAIN RESULTS:
      We tested the association of baseline levels of interleukin-6, interleukin-8,
      interleukin-10, von Willebrand factor, tumor necrosis factor-[alpha], type I and
      II soluble tumor necrosis factor receptors (sTNFR-I and -II), protein C,
      plasminogen activator inhibitor-1 (PAI-1), surfactant protein-A, surfactant
      protein-D, and intracellular adhesion molecule-1 with subsequent acute kidney
      injury. Of 876 study participants who did not have end-stage renal disease, 209
      (24%) developed acute kidney injury, defined as a rise in serum creatinine of
      >50% from baseline over the first four study days. The 180-day mortality rate for
      subjects with acute kidney injury was 58%, compared with 28% in those without
      acute kidney injury (p < .001). Interleukin-6, sTNFR-I, sTNFR-II, and PAI-1
      levels were independently associated with acute kidney injury after adjustment
      for demographics, interventions, and severity of illness. A combination of
      clinical and biological predictors had the best area under the receiver operating
      characteristic curve, and the contribution of sTNFR-I and PAI-1 to this model was
      highly significant (p = .0003). CONCLUSIONS: Elevations in PAI-1, interleukin-6,
      and the sTNFRs in subjects with acute kidney injury suggest that disordered
      coagulation, inflammation, and neutrophil-endothelial interactions play important
      roles in the pathogenesis of acute kidney injury. The combination of these
      biological and clinical risk factors may have important and additive value in
      predictive models for acute kidney injury.

PMID- 18074479
TI  - Central venous catheter infusions: a laboratory model shows large differences in
      drug delivery dynamics related to catheter dead volume.
AB  - OBJECTIVE: Central venous catheters (CVCs) are conduits for drug infusions. Dead
      volumes of different CVC lumens vary considerably. This study quantitatively
      evaluated drug delivery dynamics of CVCs in a laboratory model of continuous drug
      infusion. DESIGN: CVCs studied included a triple-lumen catheter (16-gauge and 18
      gauge lumens), the proximal infusion port of a pulmonary artery catheter, and a 9
      Fr introducer sheath, with and without a pulmonary artery catheter in the lumen.
      One syringe pump infused a carrier. A second pump infused the model drug
      methylene blue (3 mL/hr), joining the carrier immediately upstream of the CVC.
      Samples were collected every minute for quantitative analysis. SETTING:
      Laboratory model. SUBJECTS: None. INTERVENTIONS: At low fixed flow rates,
      experiments characterized drug delivery kinetics of different CVCs. Data
      collection then assessed effects of increased carrier flow. MEASUREMENT AND MAIN
      RESULTS: The time to steady-state delivery after initiation of methylene blue
      infusion differed between CVCs. At a carrier flow of 10 mL/hr, the fastest
      achievement of steady-state delivery was with the 18-gauge lumen of a triple
      lumen catheter. The 9-Fr introducer had the slowest time to achieve steady-state
      delivery. Other CVCs had intermediate kinetics. Reducing drug delivery from
      steady state to zero after cessation of methylene blue infusion was fastest with
      the 18-gauge lumen and slowest with the 9-Fr introducer. Increasing carrier flow
      rates from 10 to 60 mL/hr hastened the time to target for initiation and
      cessation of methylene blue delivery. CONCLUSIONS: Experiments demonstrate large
      differences between CVCs in the dynamics for delivery of model drug methylene
      blue. Achieving targeted steady-state delivery, and termination of a planned
      continuous drug infusion, may be far slower than typically appreciated. Delivery
      kinetics depend on the dead volume and the rate of carrier flow. Safe and
      effective management of continuous drug infusions depends on understanding the
      dynamics of the delivery system.

PMID- 18074480
TI  - Aerosolized anticoagulants ameliorate acute lung injury in sheep after exposure
      to burn and smoke inhalation.
AB  - OBJECTIVE: Acute lung injury is a detrimental complication for victims of burn
      accidents. Airway obstruction plays an important role in pulmonary dysfunction in
      these patients. In this study, we tested the hypothesis that aerosolized
      anticoagulants will reduce the degree of airway obstruction and improve pulmonary
      function in sheep with severe combined burn and smoke inhalation injury by
      preventing the formation of airway fibrin clots. DESIGN: Prospective, randomized,
      controlled, experimental animal study. SETTING: Investigational intensive care
      unit at a university hospital. SUBJECTS: Adult female sheep. INTERVENTIONS: After
      7 days of surgical recovery, sheep were given a cutaneous burn (40% of total body
      surface, third degree) and insufflated with cotton smoke (48 breaths, <40 degrees
      C) under halothane anesthesia. After injury, sheep were placed on ventilators and
      resuscitated with lactated Ringer's solution. Sheep were randomly divided into
      five groups: sham, noninjured and nontreated (n = 6); control, injured and
      aerosolized with saline (n = 6); recombinant human antithrombin (rhAT) + heparin,
      injured and aerosolized with rhAT (290 units for each) and heparin (10,000 units
      for each) (n = 6); rhAT, injured and aerosolized with rhAT alone (290 units for
      each; n = 5); and heparin, injured and aerosolized with heparin alone (10,000
      units for each; n = 5). rhAT and heparin were aerosolized every 4 hrs, starting
      at 2 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary hemodynamics
      were monitored during a 48-hr experimental time period. Control sheep developed
      multiple signs of acute lung injury. This pathophysiology included decreased
      pulmonary gas exchange and lung compliance, increased pulmonary edema, and
      extensive airway obstruction. These variables were stable in sham animals. The
      aerosolization of rhAT or heparin alone did not significantly improve
      deteriorated pulmonary gas exchange. However, aerosolization of these
      anticoagulants in combination significantly attenuated all the observed pulmonary
      pathophysiology. CONCLUSIONS: The results provide definitive evidence that
      aerosolized rhAT and heparin in combination may be a novel treatment strategy for
      pulmonary pathology in burn victims with smoke inhalation injury.

PMID- 18074481
TI  - Effects of glycogen synthase kinase-3beta inhibition on the development of
      cerulein-induced acute pancreatitis in mice.
AB  - OBJECTIVE: Glycogen synthase kinase (GSK)-3 is a ubiquitous serine-threonine
      protein kinase that participates in a multitude of cellular processes and signal
      transduction pathways. It also plays an important role in the pathophysiology of
      a number of diseases characterized by an enhanced or unregulated inflammatory
      response. Here we investigate the effects of GSK-3beta inhibition on the
      development of experimental acute pancreatitis induced by cerulein in mice.
      DESIGN: Prospective, randomized study. SETTING: University-based research
      laboratory. SUBJECTS: One-hundred and sixty anesthetized male CD mice.
      INTERVENTIONS: Pancreatitis was induced by intraperitoneal injection of cerulein
      (hourly x5, 50 microg/kg). In the treatment group, the potent and selective GSK
      3beta inhibitor 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) was
      administered 1 hr and 6 hrs after the first injection of cerulein (10 mg/kg,
      intraperitoneally). Sham groups were treated with vehicle (0.1 mL of 0.9% NaCl,
      intraperitoneally) and TDZD-8. In another set of experiments, mice were monitored
      for 24 days to determine their mortality rate. MEASUREMENTS AND MAIN RESULTS: The
      injection of cerulein resulted in acute necrotizing pancreatitis. TDZD-8
      significantly reduced the degree of pancreas injury, amylase, and lipase serum
      levels (p < .01); nuclear factor-kappaB activation (p < .01); the production of
      tumor necrosis factor-alpha and interleukin-1beta (p < .01); the expression of
      adhesion molecules and neutrophil accumulation (p < .01); the formation of oxygen
      and nitrogen-derived radicals (p < .01); the degree of lipid peroxidation (p <
      .01); the expression of transforming growth factor-beta and vascular endothelial
      growth factor (p < .01); and-ultimately-the mortality rate (p < .01).
      CONCLUSIONS: Inhibition of GSK-3beta reduces the degree of cerulein-induced acute
      pancreatitis and the associated mortality rate in mice. Blocking protein kinase
      activity may be a novel approach to treatment of this inflammatory condition.

PMID- 18074482
TI  - Caffeic acid phenethyl ester reduces mortality and sepsis-induced lung injury in
      rats.
AB  - OBJECTIVE: Sepsis and ensuing multiorgan failure continue to be the major causes
      of mortality in intensive care units. Nuclear factor (NF)-kappaB activation is
      supposed to be one of the targets in the treatment of sepsis. We studied the
      effectiveness of caffeic phenethyl ester (CAPE), a known NF-kappaB inhibitor, in
      cecal ligation and puncture (CLP)-induced sepsis and lung injury. DESIGN:
      Randomized, controlled animal study. SETTING: Research laboratory of an academic
      institution. SUBJECTS: Female Sprague-Dawley rats. INTERVENTIONS: CLP was
      performed in all rats except the rats in control and sham+CAPE groups. CAPE was
      administered to rats at the time of operation in sham+CAPE and CAPE+sepsis 0
      groups. CAPE was administered to rats in the CAPE+sepsis12 group 12 hrs after
      CLP. Eight rats from each group were killed 24 hrs after CLP. Blood was taken for
      assessment of interleukin-1, interleukin-6, interleukin-10, and tumor necrosis
      factor-alpha; the right lung was removed for histopathologic examination and the
      left lung for biochemical examination. Apoptosis, inducible nitric oxide
      synthase, heat shock protein 70, malondialdehyde, catalase, superoxide dismutase,
      and glutathione peroxidase were studied. The rest of the rats were observed for
      mortality. MEASUREMENTS AND MAIN RESULTS: Mortality was significantly decreased
      in groups that received CAPE compared with the sepsis group. All cytokine levels
      were similar to control levels only in the CAPE+sepsis12 group. Apoptosis,
      inducible nitric oxide synthase, and heat shock protein 70 evaluation were
      significantly changed between all groups in the following order: control <
      sham+CAPE< CAPE+sepsis12 < CAPE+sepsis 0 < sepsis. Malondialdehyde and catalase
      were increased in the sepsis group. CONCLUSIONS: CAPE reduced mortality in sepsis
      and improved histopathologic variables best when it was administered after the
      onset of sepsis.

PMID- 18074483
TI  - Nonconvulsive electrographic seizures after traumatic brain injury result in a
      delayed, prolonged increase in intracranial pressure and metabolic crisis.
AB  - OBJECTIVE: To determine whether nonconvulsive electrographic post-traumatic
      seizures result in increases in intracranial pressure and microdialysis
      lactate/pyruvate ratio. DESIGN: Prospective monitoring with retrospective data
      analysis. SETTING: Single center academic neurologic intensive care unit.
      PATIENTS: Twenty moderate to severe traumatic brain injury patients (Glasgow Coma
      Score 3-13). MEASUREMENTS AND MAIN RESULTS: Continuous electroencephalography and
      cerebral microdialysis were performed for 7 days after injury. Ten patients had
      seizures and were compared with a matched cohort of traumatic brain injury
      patients without seizures. The seizures were repetitive and constituted status
      epilepticus in seven of ten patients. Using a within-subject design, post
      traumatic seizures resulted in episodic increases in intracranial pressure (22.4
      +/- 7 vs. 12.8 +/- 4.3 mm Hg; p < .001) and an episodic increase in
      lactate/pyruvate ratio (49.4 +/- 16 vs. 23.8 +/- 7.6; p < .001) in the seizure
      group. Using a between-subjects comparison, the seizure group demonstrated a
      higher mean intracranial pressure (17.6 +/- 6.5 vs. 12.2 +/- 4.2 mm Hg; p <
      .001), a higher mean lactate/pyruvate ratio (38.6 +/- 18 vs. 27 +/- 9; p < .001)
      compared with nonseizure patients. The intracranial pressure and lactate/pyruvate
      ratio remained elevated beyond postinjury hour 100 in the seizure group but not
      the nonseizure group (p < .02). CONCLUSION: Post-traumatic seizures result in
      episodic as well as long-lasting increases in intracranial pressure and
      microdialysis lactate/pyruvate ratio. These data suggest that post-traumatic
      seizures represent a therapeutic target for patients with traumatic brain injury.

PMID- 18074484
TI  - Impact of passive humidification on clinical outcomes of mechanically ventilated
      patients: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Previous meta-analyses reported advantages of passive (i.e., heat and
      moisture exchangers, or HMEs) compared with active (i.e., heated humidifiers, or
      HHs) humidifiers in reducing the incidence of ventilator-associated pneumonia,
      but they did not examine the effect of these devices on mortality, length of
      intensive care unit stay, and duration of mechanical ventilation. In addition,
      relevant data were recently published. DESIGN: Meta-analysis of randomized
      controlled trials comparing HMEs with HHs for the management of mechanically
      ventilated patients to determine the impact of these devices on clinical outcomes
      of such patients. METHODS: We searched PubMed and the Cochrane Central Register
      of Controlled Trials as well as reference lists from publications, with no
      language restrictions. We estimated pooled odds ratios (ORs) and 95% confidence
      intervals (CIs), using a random effects model. RESULTS: Thirteen randomized
      controlled trials, studying 2,580 patients, were included. There was no
      difference in incidence of ventilator-associated pneumonia among patients managed
      with HMEs and HHs (OR 0.85, 95% CI 0.62-1.16). There was no difference between
      the compared groups regarding mortality (OR 0.98, 95% CI 0.80-1.20), length of
      intensive care unit stay (weighted mean differences, -0.68 days, 95% CI -3.65 to
      2.30), duration of mechanical ventilation (weighted mean differences, 0.11 days,
      95% CI -0.90 to 1.12), or episodes of airway occlusion (OR 2.26, 95% CI 0.55
      9.28). HMEs were cheaper than HHs in each of the randomized controlled trials.
      CONCLUSION: The available evidence does not support the preferential performance
      of either passive or active humidifiers in mechanical ventilation patients in
      terms of ventilator-associated pneumonia incidence, mortality, or morbidity.

PMID- 18074485
TI  - Revisional bariatric surgery for inadequate weight loss.
AB  - When behavioral or anatomic issues are not present, revisional surgery should be
      approached with a goal of treating malnutrition or enhancing excess weight loss.
      Unfortunately, no randomized controlled trials currently exist to help the
      practicing bariatric surgeon choose which revisional procedure to perform. A
      review of the available literature was undertaken and compared with our standard
      practices to see if any guidelines could be devised. At our institution, patients
      who have failed jejunal-ileal bypass are reversed in the setting of malnutrition
      and converted to a sleeve gastrectomy (SG) followed by duodenal switch (DS) as a
      second stage procedure in the setting of inadequate weight loss. After failed
      vertical banded gastroplasty (VBG), patients are converted to a Roux-en-Y gastric
      bypass (RYGBP). After failed adjustable gastric band (AGB) placement, we perform
      RYGBP. In the super-obese, we leave the band in place or convert to a DS with
      band removal. In patients with failed RYGBP, we convert our patients to DS, but
      placement of an AGB may be an acceptable option.

PMID- 18074486
TI  - Regional anesthesia and obesity.
AB  - The potential advantages of regional anesthesia include minimal airway
      intervention, less cardiopulmonary depression, excellent postoperative analgesia,
      less postoperative nausea and vomiting, and shorter recovery room and hospital
      stays. These concerns are particularly important for the obese surgical patient.
      This review discusses the application of regional anesthetic techniques in
      obesity. Further clinical studies are needed to fill the knowledge gap about
      regional anesthesia and outcome in obese and morbidly obese patients.

PMID- 18074487
TI  - Nutritional deficiencies after bariatric surgery.
AB  - A current review of nutritional complications following bariatric procedures is
      presented, focusing on the most common and clinically important deficiencies. A
      brief outline of nutritional supplementation protocol is presented, highlighting
      the need for a standardized, national or international set of guidelines for pre-
      and postoperative nutritional screening and appropriate supplementation.

PMID- 18074488
TI  - Expression of ghrelin in fundus is increased after gastric banding in morbidly
      obese patients.
AB  - BACKGROUND: Ghrelin, a 28 amino-acid acylated orexigenic peptide secreted by the
      stomach, acts on the hypothalamic arcuate nucleus which stimulates feeding
      behavior. Serum ghrelin level increases during fasting and decreases after a
      meal. Serum ghrelin is low in obese patients.Whether ghrelin is implicated in
      weight loss in obese patients after laparoscopic adjustable gastric banding
      (LAGB) is still debated. In this study, we assessed serum ghrelin level and
      gastric fundus expression before and 1 year after LAGB. METHODS: Gastric fundus
      expression of ghrelin was assessed by immunohistochemistry using a rabbit anti
      human ghrelin antibody simultaneously with serum total ghrelin levels (RIA) in 13
      obese patients (2 men and 11 women) after an overnight fast, before LAGB and 1
      year after. Immunostaining was "blindly" analyzed by a single pathologist,
      measuring the density of stained fundic cells near muscularis mucosa. RESULTS:
      Mean age of the 13 patients was 41 years, and mean baseline BMI was 46 kg/m2. Pre
      and post-LAGB gastric expression of ghrelin was analyzable in 11 patients. It
      was always identified, mostly with moderate or intense staining. Mean density of
      stained cells significantly increased 1 year after LAGB: 31/mm2 (21-38) before vs
      38/mm2 (27-57) after surgery (P<0.01). This increase did not correlate with
      changes in BMI, nor did pre- or postoperative gastric expression of ghrelin
      correlate with the corresponding serum values. CONCLUSION: We showed for the
      first time that ghrelin expression assessed by immunohistochemistry was present
      in the fundus of all 11 obese patients and that it was significantly increased 1
      year after LAGB, which would exclude a pathogenetic role of ghrelin in weight
      loss after LAGB.

PMID- 18074489
TI  - Evaluation of the excluded stomach by double-balloon endoscopy after laparoscopic
      Roux-en-Y gastric bypass.
AB  - BACKGROUND: Morbid obesity has become a serious health problem. We have been
      performing laparoscopic Roux-en-Y gastric bypass (LRYGBP) for morbid obesity
      since February 2002. Although LRYGBP ameliorates complications of morbid obesity,
      postoperative investigation of the excluded stomach is difficult. In patients
      with a family history of gastric cancer, resection of the bypassed stomach is
      sometimes added, but this requires longer operating time. There are two problems
      associated with LRYGBP: the high rate of gastric cancer in Japan, and how to
      investigate the excluded stomach. METHODS: To resolve these problems, we
      introduced double-balloon intestinal endoscopy. We report double-balloon
      endoscopy (DBE) in 4 patients. RESULTS: No problems with advancing the endoscope
      were encountered during observation. We used an overtube to insert the scope
      further in order to avoid forming redundant loops in the small intestine, and two
      balloons to grip the intestinal wall. Although performing DBE involves a learning
      curve, there were no major obstacles to passage of the scope into the esophagus,
      small gastric pouch, lifted jejunum, the jejunojejunal anastomosis, Y-loop,
      duodenum and excluded stomach. CONCLUSION: Use of the double-balloon technique
      makes it possible to observe the GI tract after laparoscopic LRYGBP irrespective
      of the length between the gastrojejunostomy and the jejunojejunostomy.

PMID- 18074490
TI  - 30-day readmission rates at a high volume bariatric surgery center: laparoscopic
      adjustable gastric banding, laparoscopic gastric bypass, and vertical banded
      gastroplasty-Roux-en-Y gastric bypass.
AB  - BACKGROUND: Recent studies suggest that weight loss operations may actually
      increase the costs to society due to increased hospital readmission rates. The
      purpose of this study was to determine the 30-day readmission rates following
      bariatric operations at a high volume bariatric surgery program. METHODS: Records
      for all patients undergoing bariatric operations during a 3-year period were
      harvested from the hospital electronic medical database. All hospital
      readmissions within 30 days of surgery were reviewed to determine the cause,
      demographics, and patient characteristics. Logistic regression analysis assessed
      the impact of various factors on the risk of readmission. RESULTS: 2,823
      consecutive patients were identified using the corrected operative log. Of these
      patients, 165 (5.8%) patients required 184 (6.5%) readmissions within 30 days of
      their index bariatric operation. Laparoscopic adjustable gastric banding (LAGB)
      had the lowest patient readmission rate of 3.1%; vertical banded gastroplasty
      Roux-en-Y gastric bypass (VBG-RYGBP) 6.8% and Laparoscopic Roux-en-Y gastric
      bypass (LRYGBP) 7.3%. Technical considerations were the most common cause for
      readmission (41% of readmissions). White race and undergoing LAGB decreased the
      odds for readmission, while total operating-room time >120 minutes, initial
      hospital stay of >3 days and deep venous thrombosis increased the odds for
      readmission. CONCLUSION: This study found an overall 30-day readmission rate of
      6.5% following bariatric operations at a high volume bariatric surgery program.
      This study supports the concept of bariatric surgery Centers of Excellence and
      accreditation of Bariatric Surgery Programs based on hospital volume of bariatric
      operations.

PMID- 18074491
TI  - Gastric tube volume after duodenal switch and its correlation to short-term
      weight loss.
AB  - BACKGROUND: Bariatric operations may have a restrictive and a malabsorptive
      component. The restrictive component is considered key for short-term weight
      loss. However, there are important volume discrepancies between gastric
      reservoirs in different bariatric surgical techniques, which questions the real
      meaning of the restrictive part of the operation. We have investigated the
      relationship between residual gastric volume after sleeve gastrectomy in duodenal
      switch (DS) and weight loss over the first postoperative year. METHODS: 14
      patients submitted to a modified DS and one patient submitted to a sleeve
      gastrectomy were studied. All patients had an abdominal CT performed between the
      third and the ninth postoperative month to measure residual gastric volume.
      Gastric tube volume was correlated to early postoperative weight loss. RESULTS:
      Mean excess BMI loss was 75% at 12 months. Mean gastric tube volume was 208 cc.
      Gastric volume was not related to preoperative weight or BMI; instead, it was
      directly related to patient's height. There was no statistical relation between
      gastric volume and weight loss at 3, 6, 9 or 12 months after the operation.
      CONCLUSION: After DS, gastric tube volume is not directly related to weight
      changes. Other factors could have influence on intake restriction, such as
      gastric tube compliance or different mechanisms of satiety induction, because no
      differences in weight loss were observed between narrow tubes and wider ones,
      despite important variations in volume.

PMID- 18074493
TI  - Abdominal lipectomy and mesh repair of midline periumbilical hernia after
      bariatric surgery: how to spare the umbilicus.
AB  - BACKGROUND: Abdominal lipectomy is becoming an increasingly common surgical
      procedure in patients with esthetic deformities resulting from massive weight
      loss induced by bariatric surgery. Sometimes a midline incisional hernia coexists
      with the pendulus abdomen. Herein presented is a technique to perform a
      retromuscular mesh repair of the incisional hernia while sparing the umbilicus.
      METHODS: The abdominal lipectomy with concomitant retro-muscular mesh repair of a
      midline incisional hernia is done sparing the vascular supply of the umbilicus on
      one side only. RESULTS: 5 consecutive women with pendulus abdomen resulting from
      bariatric surgery-induced massive weight loss and concomitant midline incisional
      hernia underwent abdominal lipectomy and incisional hernia mesh repair. Mean BMI
      was 28.6 kg/m2 (range 26-35), one patient was a smoker, and another had type 2
      diabetes requiring oral hypoglycemic agents. Two patients had had a previous
      incisional hernia repair with intraperitoneal mesh. One patient had partial
      necrosis of the umbilicus and another experienced necrosis of only the epidermis
      that recovered fully. CONCLUSIONS: The umbilicus can be safely spared during
      abdominal lipectomy with concomitant midline incisional hernia mesh repair.
      Recurrent incisional hernia and common risk factors for wound healing such as
      diabetes and obesity increase the risk of umbilical necrosis.

PMID- 18074492
TI  - Comparison of size of proximal gastric pouch and short-term weight loss following
      routine upper gastrointestinal contrast study after laparoscopic Roux-en-Y
      gastric bypass.
AB  - BACKGROUND: The authors investigated whether there is any correlation between
      gastric pouch size measured by routine upper gastrointestinal contrast study
      (UGI) after laparoscopic Roux-en-Y gastric bypass (LRYGBP) and short-term weight
      loss. METHODS: The study group consisted of 82 patients (66F, 16M) who underwent
      LRYGBP. Body mass index before surgery ranged from 35.4 to 71.7 kg/m2, with a
      mean of 47.4 kg/m2. UGI was performed 1 day after LRYGBP in all patients.
      Proximal gastric pouch size was estimated by multiplying maximal transverse and
      longitudinal diameters on AP spot image or film. Percent excess weight loss
      (%EWL) obtained at 3, 6, 12 and 24 months after surgery was used as an indicator
      of short-term results. According to the presence of contrast passage through the
      gastrojejunostomy, each patient was classified into 2 groups: Group A, negative;
      Group B, positive. RESULTS: There was no correlation between proximal gastric
      pouch size and %EWL at any point of time (P>0.05). The correlation coefficients
      calculated for 3, 6, 12 and 24 months after surgery were 0.038, 0.110, 0.015 and
      0.042, respectively (Pearson correlation test). The gastric pouch size of Group A
      was larger than that of Group B (Student t-test, P<0.001). There was no
      difference in %EWL between Groups A and B at 3 and 6 months after surgery
      (P>0.05). CONCLUSION: Pouch size area, measured by routine UGI study on the first
      postoperative day, does not influence short-term postoperative weight loss.

PMID- 18074494
TI  - Biliopancreatic diversion in rats is associated with intestinal hypertrophy and
      with increased GLP-1, GLP-2 and PYY levels.
AB  - BACKGROUND: Factors leading to weight loss and weight stabilization after
      bariatric surgery are not fully understood. The aims of this study were to
      develop an animal model for biliopancreatic diversion (BPD) and to determine
      changes in gut hormones, malabsorption and small bowel histology postoperatively.
      METHODS: 2 groups of Wistar rats underwent sham and BPD surgery. Daily
      postoperative weights and food intake were measured. 24-hour fecal collections
      were performed at Day 6 and 21. Bomb calorimetry was performed to determine the
      fecal calorific values. At day 23, levels of peptide YY (PYY), glucagon-like
      peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2) were determined and small
      bowel biopsies were taken. RESULTS: Animals in the BPD group had significant
      reduction in weight (P<0.001) and in food intake (P<0.001) compared to the sham
      group. Serum levels of PYY, GLP-1 and GLP-2 in the BPD group were significantly
      higher (P<0.005). Animals in the BPD group had significantly higher fecal energy
      content at Day 6 (P<0.001) but not at Day 21 when compared to the sham group.
      Small bowel histology confirmed the presence of significantly increased mitosis
      (P=0.03) and labelled cells (P=0.002) in the BPD animals when compared to sham.
      CONCLUSIONS: In our animal model, the higher levels of PYY, GLP-1 and GLP-2 after
      BPD may be due to gut adaptation and hypertrophy and could be important in
      inducing and maintaining weight loss after bariatric surgery.

PMID- 18074495
TI  - The decrease in serum IL-18 levels after bariatric surgery in morbidly obese
      women is a time-dependent event.
AB  - BACKGROUND: We have evaluated the impact of the reproductive status of morbidly
      obese women, and of the time elapsed since surgery, on the response of the
      proinflammatory serum cardiovascular risk marker interleukin-18 (IL-18) to the
      sustained and marked weight loss achieved after bariatric surgery. METHODS: Serum
      IL-18 levels were measured in 33 morbidly obese women before bariatric surgery
      and after losing at least 15% of the initial weight, irrespective of the time
      needed to achieve this goal (5 to 33 months). RESULTS: Patients lost 30.7 +/-
      7.8% of the initial weight, with a concomitant reduction of serum IL-18
      concentrations (P<0.001). A stepwise multiple regression analysis showed that the
      percentual decrease in serum IL-18 levels was determined by the interaction
      between the time elapsed since surgery and the percentual reduction of waist
      circumference (R2 = 0.333, F = 15.500, beta = 0.577, P<0.001), but not by the
      individual effects of the time elapsed since surgery, percentual body weight
      loss, percentual reduction of waist circumference, menopausal status or type of
      surgical procedure, or by the interaction between the time elapsed since surgery
      with the percentual body weight loss or with menopausal status. CONCLUSION: Serum
      IL-18 levels decrease after bariatric surgery in a time-dependent manner, in
      relation to the reduction in waist circumference. The fact that the amelioration
      of the obesity-associated inflammatory process requires time and not only weight
      loss, might contribute to explain early non-surgical cardiovascular complications
      of bariatric surgery.

PMID- 18074496
TI  - Foot drop as a complication of weight loss after bariatric surgery: is it
      preventable?
AB  - BACKGROUND: Although rare, the relationship between peroneal nerve palsy and
      weight loss has been well documented over the last decades. Of the 160 patients
      operated for persisting foot drop in our institution, weight loss was considered
      to be the major contributing factor for 78 patients (43.5%). METHODS: We compared
      patients who developed a foot drop after bariatric surgery with a control group
      of patients who underwent bariatric surgery (gastric banding) but did not develop
      peroneal neuropathy. RESULTS: 9 patients developed foot drop after bariatric
      surgery. The mean weight loss for these patients was 45 kg. Weight reduction took
      place during a mean period of 8.6 months. Our control group consists of 10
      patients. The mean weight loss of these patients was 43.8 kg, and the weight
      reduction took place during a mean period of 21.7 months. CONCLUSION: In contrast
      to earlier studies, we demonstrated that significant weight loss is correlated
      with a higher risk to develop foot drop and that the time period in which the
      weight loss is achieved is important. A rapid reduction of body weight is
      correlated with a higher risk to develop foot drop.

PMID- 18074497
TI  - Impression management or real change? Reports of depressive symptoms before and
      after the preoperative psychological evaluation for bariatric surgery.
AB  - BACKGROUND: Many bariatric surgery programs require that candidates undergo a
      preoperative mental health evaluation. Candidates may be motivated to suppress or
      exaggerate psychiatric symptoms (i.e., engage in impression management), if they
      believe doing so will enhance their chances of receiving a recommendation to
      proceed with surgery. METHOD: 237 candidates for bariatric surgery completed the
      Beck Depression Inventory-II (BDI-ll) as part of their preoperative psychological
      evaluation (Time 1). They also completed the BDI-II approximately 2-4 weeks
      later, for research purposes, after they had received the mental health
      professional's unconditional recommendation to proceed with surgery (Time 2).
      RESULTS: There was a small but statistically significant increase in mean BDI-II
      scores from Time 1 to Time 2 (11.4 vs 12.7, P<.001). Clinically significant
      changes, defined as a change from one range of symptom severity to another, were
      observed in 31.2% of participants, with significant increases in symptoms
      occurring nearly twice as often as reductions (20.7% vs 10.5%, P<.008).
      Demographic variables were largely unrelated to changes in BDI-II scores from
      Time 1 to Time 2. CONCLUSION: Approximately one-third of bariatric surgery
      candidates reported a clinically significant change in depressive symptoms after
      receiving psychological "clearance" for surgery. Possible explanations for these
      findings include measurement error, impression management, and true changes in
      psychiatric status.

PMID- 18074498
TI  - Long-term outcomes following laparoscopic adjustable gastric banding:
      postoperative psychological sequelae predict outcome at 5-year follow-up.
AB  - BACKGROUND: NICE guidelines state that patients with psychological contra
      indications should not be considered for bariatric surgery, including
      Laparoscopic Adjustable Gastric Banding (LAGB) surgery as treatment of morbid
      obesity, although no consistent correlation between psychiatric illness and long
      term outcome in LAGB has been established. This is to our knowledge the first
      study to evaluate long-term outcomes in LAGB for a full range of DSM-IV defined
      psychiatric and eating disorders, and forms part of a research portfolio
      developed by the authors aimed at defining psychological predictors of bariatric
      surgery in the short-, medium- and long-term. METHODS: Case notes of 37 subjects
      operated on between April 1997 and June 2000, who had undergone structured
      clinical interview during pre-surgical assessment to yield diagnoses of mental
      and eating disorders according to DSM-IV criteria were analyzed according to a
      set of operationally defined criteria. Statistical analysis was carried out to
      compare those with a poor outcome and those considered to have a good outcome in
      terms of psychiatric profile. RESULTS: In this group of mainly female, Caucasian
      subjects, ranging in age from 27 to 60 years, one-third were diagnosed with a
      mental disorder according to DSM-IV criteria. The development of postoperative
      DSM-IV defined binge eating disorder (BED) or depression strongly predicted poor
      surgical outcome, but pre-surgical psychiatric factors alone did not. CONCLUSION:
      Although pre-surgical psychiatric assessment alone cannot predict outcome, an
      absence of preoperative psychiatric illness should not reassure surgeons who
      should be mindful of postoperative psychiatric sequelae, particularly BED. The
      importance of providing an integrated biopsychosocial model of care in bariatric
      teams is highlighted.

PMID- 18074499
TI  - Weight loss and eating behavior following vertical banded gastroplasty.
AB  - BACKGROUND: Bariatric surgery is the treatment of choice for patients with morbid
      obesity. In addition to surgery, postoperative dietary behavior is an important
      mediator of weight loss and, therefore, critical in influencing outcome. Surgical
      treatment of obesity is not an alternative to dieting but a method to enforce
      dieting. METHODS: We evaluated early weight loss and postoperative eating
      behavior over time. Preoperatively as well as 6 months, 1 and 2 years after
      vertical banded gastroplasty (VBG), 91 patients were psychologically assessed
      using a semi-structured interview and a psychological questionnaire focusing on
      eating behavior. RESULTS: Over time, we found significant changes in weight,
      mostly in the 1st postoperative year (EWL= 52.0%); at 2 years, EWL was 61.5%.
      Patients reported substantial changes in feelings of hunger, appetite, satiety,
      and eating behavior; however, most improvements waned over time. In addition,
      there was a wide variability in changes within our patient group, and changes in
      weight loss appeared to be related to changes in restrained eating. CONCLUSION:
      VBG not only leads to considerable weight loss, but also to significant
      improvements in eating behavior, at least within 2 years. However, most
      improvements wane over time and not all patients profit in the same way.

PMID- 18074500
TI  - Prediction of successful weight reduction after bariatric surgery by data mining
      technologies.
AB  - BACKGROUND: Surgery is the only long-lasting effective treatment for morbid
      obesity. Prediction on successful weight loss after surgery by data mining
      technologies is lacking. We analyze the available information during the initial
      evaluation of patients referred to bariatric surgery by data mining methods for
      predictors of successful weight loss. METHODS: 249 patients undergoing
      laparoscopic mini-gastric bypass (LMGB) or adjustable gastric banding (LAGB) were
      enrolled. Logistic Regression and Artificial Neural Network (ANN) technologies
      were used to predict weight loss. Overall classification capability of the
      designed diagnostic models was evaluated by the misclassification costs. RESULTS:
      We studied 249 patients consisting of 72 men and 177 women over 2 years. Mean age
      was 33 +/- 9 years. 208 (83.5%) patients had successful weight reduction while 41
      (16.5%) did not. Logistic Regression revealed that the type of operation had a
      significant prediction effect (P = 0.000). Patients receiving LMGB had a better
      weight loss than those receiving LAGB (78.54% +/- 26.87 vs 43.65% +/- 26.08). ANN
      provided the same predicted factor on the type of operation but it further
      proposed that HbAlc and triglyceride were associated with success. HbAlc is lower
      in the successful than failed group (5.81 +/- 1.06 vs 6.05 +/- 1.49; P = NS), and
      triglyceride in the successful group is higher than in the failed group (171.29
      +/- 112.62 vs 144.07 +/- 89.90; P = NS). CONCLUSION: Artificial neural network is
      a better modeling technique and the overall predictive accuracy is higher on the
      basis of multiple variables related to laboratory tests. LMGB, high preoperative
      triglyceride level, and low HbAlc level can predict successful weight reduction
      at 2 years.

PMID- 18074501
TI  - Behavior of insulin sensitivity and its relation to leptin and tumor necrosis
      factor-alpha in obese women undergoing liposuction: 6-month follow-up.
AB  - BACKGROUND: Metabolic syndrome is a group of pathological processes which involve
      insulin resistance, a biochemical and molecular disorder. Obesity appears to be
      the most frequent clinical component in metabolic syndrome. Subcutaneous fat,
      independent from visceral fat, is still controversial as a marker of the
      pathophysiology of insulin resistance. METHODS: An open parallel-group clinical
      trial was performed of 12 women (age 30-40 years), with BMI from 30-33 kg/m2 and
      fasting glucose < or =110 mg/dl. 6 women were included in the "liposuction plus
      diet" group, and 6 were included in the "diet-only" group. Metabolic profile,
      including insulin tolerance test (ITT), leptin and tumor necrosis factor alpha
      (TNFalpha), was performed at baseline, 1 and 6 months in both groups.
      Subcutaneous and visceral fat was quantified with spiral tomography at baseline
      and after 6 months. Friedman and Wilcoxon test were used for intra-group
      differences, Mann-Whitney U for differences between groups, and Spearman test for
      correlation, with significance set at P<0.05. RESULTS: No difference existed
      between groups regarding clinical characteristics and metabolic profile. In the
      liposuction group, the increase in insulin sensitivity was (3.8+/-0.86, 3.1+/
      0.85, 4.5+/-1.02 %/min, P=0.08. Insulin sensitivity did not correlate with
      subcutaneous fat, leptin, or TNFalpha. Leptin diminished at 1 month (52.7+/-6.04
      vs 31.6+/-11.9), P=0.028, and correlated with the subcutaneous fat (r=0.957). In
      the diet-only group, TNFalpha diminished at 6 months, P=0.046. CONCLUSION:
      Subcutaneous abdominal fat correlates with leptin; nevertheless, it is a weak
      marker for TNFalpha and insulin sensitivity.

PMID- 18074503
TI  - A case study from the advanced bariatric life support initiative: pulmonary
      embolism after laparoscopic gastric bypass.
AB  - Pulmonary embolism is the leading cause of death after bariatric surgery and
      represents one of the many potential life-threatening conditions after bariatric
      surgery. The Advanced Bariatric Life Support (ABLS) initiative was developed to
      teach practising bariatric surgeons, emergency physicians, and allied health
      professionals the need for accurate and timely diagnosis and management of life
      threatening bariatric surgery complications. This case study was derived from the
      ABLS file and discusses the difficulty in differentiating between two major
      complications after gastric bypass--pulmonary embolism vs leak. Accurate
      diagnosis and expeditious treatment are of utmost importance to prevent death
      associated with these serious bariatric surgical complications.

PMID- 18074502
TI  - The comparative effects of bariatric surgery on weight and type 2 diabetes.
AB  - BACKGROUND: Epidemiological evidence confirms that risk of developing type 2
      diabetes is related to weight gain. Weight reduction is beneficial as relative
      risk is reduced to 0.13 for weight loss >20 kg. This raises the question of
      effectiveness of bariatric surgery on 1) weight loss and 2) diabetes-related
      outcomes in morbidly obese patients. METHODS: We reviewed the literature using
      Medline. Only 2 meta-analyses reporting on both outcomes were included, as well
      as 50 systematic reviews or primary studies. RESULTS: Meta-analyses mainly based
      on case series data as well as controlled studies confirm that bariatric surgery
      is highly effective in obtaining weight reduction in morbidly obese patients up
      to 60% of the excess weight, along with resolution of preoperative diabetes in
      more than 75% of cases. Among bariatric surgery techniques, malabsorptive
      procedures (biliopancreatic diversion and gastric bypass) appear to be more
      effective on both outcomes than restrictive procedures (gastroplasty and gastric
      banding). CONCLUSION: Even if more studies are needed to confirm current
      evidence, bariatric surgery is effective for controlling diabetes. It appears as
      an efficient strategy from economic modeling due to savings from reduction in
      diabetes-related costs.

PMID- 18074504
TI  - Endoscopic hemostasis using endoclip in early gastrointestinal hemorrhage after
      gastric bypass surgery.
AB  - Roux-en-Y gastric bypass (RYGBP) is the most commonly performed bariatric
      operation in the USA. In the early postoperative stage, gastrointestinal (GI)
      bleeding is an infrequent but potentially serious complication that usually
      results from bleeding at the gastrojejunostomy staple-line. Observant management
      with transfusion for stable patients and surgical exploration for unstable
      patients is typically recommended for early GI bleeding. We hypothesized that use
      of endoclips, which do not cause thermal injury to the surrounding tissues (or
      anastomosis), may be preferable to thermal approaches which could cause tissue
      injury. We report 2 cases of early GI bleeding after RYGBP that were successfully
      managed with endoclip application to bleeding lesions. Emergent endoscopy was
      performed, and major stigmata such as active spurting vessel and adherent clot
      were noted at the gastrojejunostomy staple-lines. Endoscopic hemostasis using
      endoclips was readily applied to bleeding lesions at staple-lines. Primary
      hemostasis was achieved, and there was no recurrent bleeding or complication. We
      conclude that therapeutic endoscopy can be performed safely for early bleeding
      after RYGBP. In patients with early bleeding after RYGBP, use of endoclips is
      mechanistically preferable to other options.

PMID- 18074505
TI  - Cancer in the bypassed stomach presenting early after gastric bypass.
AB  - Gastric carcinoma in the bypassed stomach after Roux-en-Y gastric bypass (RYGBP)
      is rare but has been reported. The time from RYGBP to the presentation of cancer
      has ranged from 5 to 22 years postoperatively in the literature. A major concern
      with the current technique for RYGBP is the exclusion of the bypassed stomach and
      difficulty in surveillance. Thus, some surgeons recommend routine preoperative
      evaluation via endoscopy. Although most findings are benign, abnormalities are
      frequently discovered during screening endoscopy in bariatric surgery patients.
      We present a 45-year-old woman who was discovered to have disseminated gastric
      cancer involving the excluded bypassed stomach following an open RYGBP.
      Preoperative upper endoscopy was not performed. This case illustrates the
      importance of endoscopic evaluation prior to RYGBP and signifies the need for a
      high index of suspicion in order to recognize this problem at an early stage.

PMID- 18074506
TI  - Appetite suppression and weight loss incidental to spinal cord stimulation for
      pain relief.
AB  - Spinal cord stimulation (SCS) uses electrical stimulation of the dorsal columns
      of the spinal cord to prevent the perception of intractable neuropathic pain
      signals, but its mechanisms and consequences of use are poorly understood. Two
      overweight female patients who were implanted with SCS systems (Precision;
      Advanced Bionics/Boston Scientific, Valencia, CA) reported better than 50% relief
      of their chronic back and leg pain. Unexpectedly, SCS stimulation was also
      associated with a tingling sensation in the viscera and a reduction in appetite.
      Both patients were thus able to reduce food intake at mealtimes and had lost
      about 9 kg in the first 4 months of SCS use, despite denying changes in exercise
      habits. The mechanism by which SCS can reduce the desire for food is unknown, but
      this and similar neuromodulation techniques may hold promise for weight loss in
      patients who fail other treatments or are not healthy enough for surgery.

PMID- 18074507
TI  - Reporting weight loss.

PMID- 18074508
TI  - [Classification and mechanism of adverse drug reaction].
AB  - A response to a drug which is noxious and unintended and which occurs at doses
      normally used in man for prophylaxis, diagnosis or therapy of disease or for
      modification of physiological function. (WHO technical report 498, 1972). All
      noxious and unintended responses to a medicinal product related to any dose
      should be considered adverse drug reactions. The phrase "responses to medicinal
      products" means that a causal relationship between a medicinal product and an
      adverse event is at least a reasonable possibility, i.e. the relationship cannot
      be ruled out. (ICH E2A, 1995).

PMID- 18074509
TI  - [Factors affecting the occurrence of adverse drug reactions].

PMID- 18074510
TI  - [Prediction of adverse drug reactions based on genomic information].

PMID- 18074511
TI  - [Diagnosis of adverse drug reaction].

PMID- 18074512
TI  - [Precautions for use of pharmaceuticals].

PMID- 18074513
TI  - [Precautions in use of drugs for Infants and children].

PMID- 18074514
TI  - [Precautions in use of drugs for pregnancy and lactating women].

PMID- 18074515
TI  - [Precautions in use of drugs for elderly patients].

PMID- 18074517
TI  - [Pharmacokinetics and administration of drugs in patients with hepatic failure].

PMID- 18074516
TI  - [Management of adverse drug reaction in patients with allergic diseases].

PMID- 18074518
TI  - [Safe drug prescribing for patients with renal failure].

PMID- 18074519
TI  - [Reporting system for adverse drug reactions and infections].

PMID- 18074520
TI  - [Classification criteria for severity of adverse drug reactions].

PMID- 18074521
TI  - [Adverse health effect relief services].

PMID- 18074522
TI  - [Drug-induced nephropathy].

PMID- 18074523
TI  - [Drug-induced hematological disorders].

PMID- 18074524
TI  - [Adverse effects of medicinal drugs on the skin].

PMID- 18074525
TI  - [Cardiotoxicity of non-cardiac drugs].

PMID- 18074526
TI  - [Drug-induced respiratory disorders].

PMID- 18074528
TI  - [Psychiatric and neurological side effects of pharmaceutical preparations].

PMID- 18074527
TI  - [Drug-induced gastrointestinal disorder].

PMID- 18074529
TI  - [Deadly drug interactions].

PMID- 18074530
TI  - [Adverse effects of cardiovascular agents].

PMID- 18074531
TI  - [Adverse effects of calcium antagonists and beta-blockers].

PMID- 18074532
TI  - [Adverse effects of ACE inhibitors, ARB, diuretics, and alpha1 blockers].

PMID- 18074533
TI  - [Adverse effects of lipid-lowering medications].

PMID- 18074534
TI  - [Adverse effects of insulin].

PMID- 18074535
TI  - [Adverse effects of sulfonylurea drugs].

PMID- 18074536
TI  - [Adverse effects of alpha-glucosidase inhibitors].

PMID- 18074537
TI  - [Adverse effects of insulin sensitisers and biguanides].

PMID- 18074538
TI  - [Side effects of gastric muco-protective agents].

PMID- 18074539
TI  - [Adverse effects of gastric acid suppressive drugs].

PMID- 18074540
TI  - [Nonsteroidal anti-inflammatory drugs].

PMID- 18074541
TI  - [Adverse effects of conventional DMARDs and biologic DMARDs].

PMID- 18074542
TI  - [Adverse effects of glucocorticoids].

PMID- 18074543
TI  - [Adverse effects of antibiotics].

PMID- 18074544
TI  - [Adverse effects of antiviral agents].

PMID- 18074545
TI  - [Adverse effects of psychotropic agents].

PMID- 18074546
TI  - [Side effects of inhaled corticosteroids].

PMID- 18074547
TI  - [Adverse effects of chemical mediator release inhibitors].

PMID- 18074548
TI  - [Adverse effects of H1-receptor antagonists].

PMID- 18074549
TI  - [Gastrointestinal complication of cancer chemotherapy].

PMID- 18074550
TI  - [Myelosuppression due to antineoplastic agents].

PMID- 18074551
TI  - [Chemotherapy-induced cutaneous complications, alopecia, and edema].

PMID- 18074552
TI  - [Interstitial pneumonia due to adverse effect of antineoplastic agents].

PMID- 18074553
TI  - [Adverse events of drugs for the treatment of osteoporosis].

PMID- 18074554
TI  - [Anaphylaxis due to drugs].

PMID- 18074555
TI  - [Drug-induced shock].

PMID- 18074556
TI  - [Drug-induced lupus erythematosus].

PMID- 18074557
TI  - [Drug-induced malignant hyperthermia].

PMID- 18074558
TI  - [Drug-induced neuroleptic malignant syndrome].

PMID- 18074559
TI  - [Drug-induced hypersensitivity syndrome].

PMID- 18074560
TI  - [Drug-induced urticaria].

PMID- 18074561
TI  - [Drug-induced photosensitivity].

PMID- 18074562
TI  - [Drug-induced Angioedema].

PMID- 18074563
TI  - [Drug dependence syndrome as a side effect of medical drug use].

PMID- 18074564
TI  - [Drug-induced abnormal behaviors].

PMID- 18074565
TI  - [Drug-induced depression].

PMID- 18074566
TI  - [Drug-induced leukoencephalopathy].

PMID- 18074567
TI  - [Drug-induced aseptic meningitis].

PMID- 18074568
TI  - [Drug-induced visual disturbance].

PMID- 18074569
TI  - [Drug-induced myopathies].

PMID- 18074570
TI  - [Drug-induced osteoporosis].

PMID- 18074571
TI  - [Drug-induced interstitial pneumonia].

PMID- 18074572
TI  - [Drug-induced pulmonary infiltration with eosinophilia, eosinophilic pneumonia].

PMID- 18074573
TI  - [Drug-induced asthma].

PMID- 18074574
TI  - [Drug-induced respiratory depression].

PMID- 18074575
TI  - [Drug-induced long QT syndrome].

PMID- 18074576
TI  - [Ventricular proarrhythmia in the rhythm-control therapy for atrial
      fibrillation].

PMID- 18074577
TI  - [Drug-induced myocarditis].

PMID- 18074578
TI  - [Drug-induced cardiomyopathy].

PMID- 18074579
TI  - [Drug-induced heart failure].

PMID- 18074580
TI  - [Thrombosis--adverse effect of drugs].

PMID- 18074581
TI  - [Drug-induced pancytopenia].

PMID- 18074582
TI  - [Drug-induced neutropenia (agranulocytosis)].

PMID- 18074583
TI  - [Drug-induced thrombocytopenia].

PMID- 18074584
TI  - [Drug-induced thrombotic thrombocytopenic purpura].

PMID- 18074585
TI  - [Drug-induced hemolytic anemia].

PMID- 18074586
TI  - [Aplastic anemia associated with drug].

PMID- 18074587
TI  - [Drug-induced megaloblastic anemia].

PMID- 18074588
TI  - [Drug-induced coagulation disorders].

PMID- 18074589
TI  - [Drug-induced disseminated intravascular coagulation (DIC)].

PMID- 18074590
TI  - [Drug-induced taste disorder].

PMID- 18074591
TI  - [Drug-induced esophagitis, esophageal ulcer, gastro-duodenal ulcer, and small
      intestinal ulcer].

PMID- 18074592
TI  - [Drug-induced ileus].

PMID- 18074593
TI  - [Ulcerative colitis].

PMID- 18074594
TI  - [Drug-induced pseudomembranous colitis].

PMID- 18074595
TI  - [Drug-induced pancreatitis].

PMID- 18074596
TI  - [Abnormality of liver functional test in patients with drug-induced liver
      injury].

PMID- 18074597
TI  - [Drug-induced cholestasis].

PMID- 18074598
TI  - [Drug-induced hepatitis].

PMID- 18074599
TI  - [Fulminant hepatitis].

PMID- 18074600
TI  - [Drug-induced nephropathy].

PMID- 18074602
TI  - [Drug-induced renal failure].

PMID- 18074601
TI  - [Tubulointerstitial nephritis associated with drug reactions].

PMID- 18074603
TI  - [Drug-induced nephrotic syndrome].

PMID- 18074604
TI  - [Drug-induced acidosis].

PMID- 18074605
TI  - [Drug-induced hypoglycemia].

PMID- 18074606
TI  - [Drug-induced diabetes].

PMID- 18074607
TI  - [Drug-induced syndrome of inappropriate secretion of ADH].

PMID- 18074608
TI  - [Drug-induced pseudoaldosteronism].

PMID- 18074609
TI  - For the patient. Understanding how lifestyle choices affect chronic disease in
      Montreal.

PMID- 18074610
TI  - For the patient. Obesity, uric acid, and high blood pressure.

PMID- 18074611
TI  - For the patient. Stroke survivors: reduce risk of heart disease by walking and
      treadmill exercise.

PMID- 18074612
TI  - For the patient. Black women with preeclampsia/eclampsia stay longer in Florida
      hospitals than White women do.

PMID- 18074613
TI  - Chest wall abscess due to aspiration of grass inflorescence.

PMID- 18074614
TI  - [Do health services benefit from exchange of preparations in pharmacies?].

PMID- 18074615
TI  - [Personal physician or personal as a physician, what a difference].

PMID- 18074616
TI  - Shift happens.

PMID- 18074617
TI  - Anisotropic imaging performance in breast tomosynthesis.
AB  - We describe the anisotropy in imaging performance caused by oblique x-ray
      incidence in indirect detectors for breast tomosynthesis based on columnar
      scintillator screens. We use MANTIS, a freely available combined x-ray, electron,
      and optical Monte Carlo transport package which models the indirect detection
      processes in columnar screens, interaction by interaction. The code has been
      previously validated against published optical distributions. In this article,
      initial validation results are provided concerning the blur for particular
      designs of phosphor screens for which some details with respect to the columnar
      geometry are available from scanning electron microscopy. The polyenergetic x-ray
      spectrum utilized comes from a database of experimental data for three different
      anode/filter/kVp combinations: Mo/Mo at 28 kVp, Rh/Rh at 28 kVp, and W/Al at 42
      kVp. The x-ray spectra were then filtered with breast tissue (3, 4, and 6 cm
      thickness), compression paddle, and support base, according to the oblique paths
      determined by the incidence angle. The composition of the breast tissue was
      50%/50% adipose/glandular tissue mass ratio. Results are reported on the pulse
      height statistics of the light output and on spatial blur, expressed as the
      response of the detector to a pencil beam with a certain incidence angle. Results
      suggest that the response is nonsymmetrical and that the resolution properties of
      a tomosynthesis system vary significantly with the angle of x-ray incidence. In
      contrast, it is found that the noise due to the variability in the number of
      light photons detected per primary x-ray interaction changes only a few percent.
      The anisotropy in the response is not less in screens with absorptive backings
      while the noise introduced by variations in the depth-dependent light output and
      optical transport is larger. The results suggest that anisotropic imaging
      performance across the detector area can be incorporated into reconstruction
      algorithms for improving the image quality of breast tomosynthesis. This study
      also demonstrates that the assessment of image quality of breast tomosynthesis
      systems requires a more complete description of the detector response beyond
      local, center measurements of resolution and noise that assume some degree of
      symmetry in the detector performance.

PMID- 18074618
TI  - Pheromone binding and inactivation by moth antennae.
AB  - The antennae of male silk moths are extremely sensitive to the female sex
      pheromone such that a male moth can find a female up to 4.5 km away. This
      remarkable sensitivity is due to both the morphological and biochemical design of
      these antennae. Along the branches of the plumose antennae are the sensilla
      trichodea, each consisting of a hollow cuticular hair containing two unbranched
      dendrites bathed in a fluid, the receptor lymph ,3. The dendrites and receptor
      lymph are isolated from the haemolymph by a barrier of epidermal cells which
      secreted the cuticular hair. Pheromone molecules are thought to diffuse down 100
      A-wide pore tubules through the cuticular wall and across the receptor lymph
      space to receptors located in the dendritic membrane. To prevent the accumulation
      of residual stimulant and hence sensory adaptation, the pheromone molecules are
      subsequently inactivated in an apparent two-step process of rapid 'early
      inactivation' followed by much slower enzymatic degradation. The biochemistry
      involved in this sequence of events is largely unknown. We report here the
      identification of three proteins which interact with the pheromone of the wild
      silk moth Antheraea polyphemus: a pheromone-binding protein and a pheromone
      degrading esterase, both uniquely located in the pheromone-sensitive sensilla;
      and a second esterase common to all cuticular tissues except the sensilla.

PMID- 18074619
TI  - [Colonial psychiatry in New Caledonia].

PMID- 18074620
TI  - The principles of the Ponseti method in the treatment of congenital clubfoot.
AB  - We present Ignatio Ponseti's approach to idiopathic clubfoot management and its
      biological basis. The key principles of the Ponseti method of treatment are 1.
      All deformity components are corrected simultaneously except equinus, which is
      corrected last, usually by percutaneous Achilles tenotomy. 2. The correction is
      maintained by external foot rotation around the head of the talus. 3. The
      excavatus is corrected by supination of the first ray of the foot. 4. The
      corrections are performed weekly and after 4-5 weeks of treatment a percutaneous
      Achilles tenotomy is performed in local or general anaesthesia. 5. After another
      3 weeks of plaster cast immobilisation, a Dennis Brown brace is used to keep the
      correction until 4-5 years of life.

PMID- 18074621
TI  - Trip to Haiti changes lives of patients and volunteers.

PMID- 18074622
TI  - Sanity marked by insanity: seeing psychiatry through art.

PMID- 18074623
TI  - Hip fracture and antipsychotics.

PMID- 18074624
TI  - Monoamine oxidase is not in synapse.

PMID- 18074625
TI  - [Great interest at the 'Oncology controversy' Congress].

PMID- 18074626
TI  - Medical toxicology and public health--update on research and activities at the
      Centers for Disease Control and Prevention and the Agency for Toxic Substances
      and Disease Registry.

PMID- 18074627
TI  - Have you recruited nurses without oncology experience?

PMID- 18074628
TI  - Outer mitochondrial membrane protein degradation by the proteasome.
AB  - Protein turnover is used for regulatory processes and to eliminate superfluous,
      denatured or chemically inactivated polypeptides. Mitochondrial proteins may be
      particularly susceptible to damage induced by reactive oxygen species and several
      pathways of mitochondrial proteolysis have been illuminated. However, in contrast
      to matrix and inner mitochondrial membrane protein degradation, little is known
      about the turnover of integral outer mitochondrial membrane (OMM) proteins or the
      mechanisms involved. We have found that pheromone treatment of Saccharomyces
      cerevisiae induces the proteasome-dependent elimination of the OMM spanning
      protein, Fzo1, from the mitochondria and that Fzo1 is ubiquitylated while still
      associated with the membrane. These characteristic processing steps are similar
      to those of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway
      suggesting the term OMMAD, outer mitochondrial membrane-associated degradation,
      to describe the process. ERAD is dependent upon ER membrane spanning RING domain
      E3 ubiquitin ligases suggesting that certain E3 ligases in the OMM may also
      regulate OMMAD. This led us to clone and characterize all 54 predicted human gene
      products that contain both RING domains and predicted membrane spanning domains.
      A surprising number of these localize to mitochondria where some may control
      OMMAD. Some of these mitochondrial RING domain proteins also regulate
      mitochondrial morphology, indicating a critical role of ubiquitin signalling in
      the maintenance of mitochondrial homeostasis.

PMID- 18074629
TI  - PA-GFP: a window into the subcellular adventures of the individual mitochondrion.
AB  - Mitochondrial connectivity is characterized by matrix lumen continuity and by
      dynamic rewiring through fusion and fission events. While these mechanisms
      homogenize the mitochondrial population, a number of studies looking at
      mitochondrial membrane potential have demonstrated that mitochondria exist as a
      heterogeneous population within individual cells. To address the relationship
      between mitochondrial dynamics and heterogeneity, we tagged and tracked
      individual mitochondria over time while monitoring their mitochondrial membrane
      potential (deltapsi(m)). By utilizing photoactivatible-GFP (PA-GFP), targeted to
      the mitochondrial matrix, we determined the boundaries of the individual
      mitochondrion. A single mitochondrion is defined by the continuity of its matrix
      lumen. The boundaries set by luminal continuity matched those set by electrical
      coupling, indicating that the individual mitochondrion is equipotential
      throughout the entire organelle. Similar results were obtained with PA-GFP
      targeted to the inner membrane indicating that matrix continuity parallels inner
      membrane continuity. Sequential photoconversion of matrix PA-GFP in multiple
      locations within the mitochondrial web reveals that each ramified mitochondrial
      structure is composed of juxtaposed but discontinuous units. Moreover, as many as
      half of the events in which mitochondria come into contact, do not result in
      fusion. While all fission events generated two electrically uncoupled
      discontinuous matrices, the two daughter mitochondria frequently remained
      juxtaposed, keeping the tubular appearance unchanged. These morphologically
      invisible fission events illustrate the difference between mitochondrial fission
      and fragmentation; the latter representing the movement and separation of
      disconnected units. Simultaneous monitoring of deltapsi(m) of up to four
      individual mitochondria within the same cell revealed that subcellular
      heterogeneity in deltapsi(m) does not represent multiple unstable mitochondria
      that appear 'heterogeneous' at any given point, but rather multiple stable, but
      heterogeneous units.

PMID- 18074630
TI  - Multiple functions of mitochondria-shaping proteins.
AB  - Mitochondria are complex organelles whose internal structure and cytosolic
      organization is controlled by a growing number of 'mitochondria-shaping'
      proteins. These include mitochondrial proteins such as the large dynamin-related
      GTPases Mitofusin (Mfn) 1 and 2, Optic Atrophy 1 (Opa1); as well as the cytosolic
      dynamin-related protein 1 (Drp1) and its receptor on the outer mitochondrial
      membrane Fis1. These proteins influence not only the shape of mitochondria, but
      also the function of the organelle and eventually integrated cellular signalling
      cascades, including apoptosis. We undertook a genetic approach to elucidate the
      function and regulation of these proteins. Opa1 is involved in the regulation of
      mitochondrial fusion, by co-operating with Mfn1. Moreover, Opa1 independently
      from mitochondrial fusion regulates the crista remodelling pathway of apoptosis.
      Oligomers of a membrane bound and a soluble form of Opa1, produced by Parl, an
      inner membrane rhomboid protease, are disrupted early during apoptosis, leading
      to remodelling of the mitochondrial cristae and redistribution of the
      mitochondrial cytochrome c. The importance of this pathway is substantiated by
      the phenotype of the Parl-/- mouse, which displays excess apoptosis in multiple
      tissues. Cells lacking Parl are more susceptible to apoptotic stimuli and the
      reintroduction of a soluble form of Opa1 rescues their phenotype.

PMID- 18074631
TI  - Transcriptional control of mitochondrial energy metabolism through the PGC1
      coactivators.
AB  - The PGC1 transcriptional coactivators are major regulators of several crucial
      aspects of energy metabolism. PGC1alpha controls many aspects of oxidative
      metabolism, including mitochondrial biogenesis and respiration through the
      coactivation of many nuclear receptors, and factors outside the nuclear receptor
      family. ERRalpha, NRF1 and NRF2 are key targets of the PGC1s in mitochondrial
      biogenesis. We have recently addressed the question of the role of PGC1
      coactivators in the metabolism of reactive oxygen species (ROS). We now show that
      PGC1alpha and beta are induced when cells are given an oxidative stressor, H2O2.
      In fact, experiments with either genetic knockouts or RNAi for the PGC1s show
      that the ability of ROS to induce a ROS scavenging programme depends entirely on
      the PGC1s. This includes genes encoding mitochondrial proteins like SOD2, but
      also includes cytoplasmic proteins such as catalase and GPX1. Cells lacking
      PGC1alpha are hypersensitive to death from oxidative stress caused by H2O2 or
      paraquat. Mice deficient in PGC1alpha get excessive neurodegeneration when given
      kainic acid-induced seizures or MPTP, which causes Parkinsonism. These data show
      that the PGC1s are key modulators of mitochondrial biology and important
      protective molecules against ROS generation and damage. The implications of this
      for diabetes and neurodegenerative diseases are discussed.

PMID- 18074632
TI  - Novel uncoupling proteins.
AB  - Mitochondria are incompletely coupled because of proton leaks that short-circuit
      oxidative phosphorylation. Basal proton leak is unregulated and is associated
      with the presence (but not catalytic activity) of the adenine nucleotide
      translocase. Inducible proton leak is regulated and is catalysed by the adenine
      nucleotide translocase and specific uncoupling proteins (UCPs). UCP1 catalyses
      proton conductance in mammalian brown adipose tissue. It is activated by fatty
      acids, which overcome nucleotide inhibition. UCP2, UCP3 and UCPs from birds, fish
      and plants also catalyse proton conductance that is inhibited by nucleotides.
      However, they require activation by superoxide or other reactive oxygen species
      (ROS). The mechanism of proton transport by the UCPs is unresolved. UCPs may also
      transport fatty acids or fatty acyl peroxides. Several physiological functions of
      UCPs are postulated. (1) UCP1 is specialised for thermogenesis; UCP3 and avian
      UCPs possibly share this function. (2) UCPs may attenuate ROS production and
      protect against oxidative damage, degenerative diseases and ageing. (3) UCP3 may
      catalyse fatty acid transport. (4) UCP2 has a signalling role in pancreatic beta
      cells, where it attenuates insulin secretion. Other roles remain to be
      discovered.

PMID- 18074633
TI  - Mitochondria as generators and targets of nitric oxide.
AB  - Mitochondrial biochemistry is complex, expanding from oxidative phosphorylation,
      lipid catabolism and haem biosynthesis, to apoptosis, calcium homeostasis, and
      production of reactive oxygen and nitrogen species, including nitric oxide (NO).
      This molecule is produced by a mitochondrial nitric-oxide synthase (mtNOS). The
      rates of consumption and production determine the steady-state concentration of
      NO at subcellular levels, leading to the regulation of several mitochondrial
      events. Temporospatial processes tightly regulate the production of NO in
      mitochondria to maximize target effects and minimize deleterious reactions.
      Temporal regulatory mechanisms of mtNOS include activation by calcium and
      transcriptional/translational regulation. Calcium-activated mtNOS inhibits
      mitochondrial respiration. This regulation antagonizes the effects of calcium on
      matrix calcium-dependent dehydrogenases, preventing the formation of anoxic foci.
      Temporal regulation of NO production by intracellular calcium signalling requires
      the understanding of the heterogeneous intracellular calcium response and calcium
      distribution. NO production in mitochondria is spatially regulated by subcellular
      localization of mtNOS (e.g. acylation and protein-protein interactions), in
      addition to transcriptional regulation. Given the short half-life of NO in
      biological systems, organelle localization of mtNOS is crucial for NO to function
      as a signal molecule. These temporospatial processes are biologically important
      to allow NO to act as an effective signal molecule to regulate mitochondrial
      events.

PMID- 18074634
TI  - Calcium signalling and mitochondrial motility.
AB  - Intracellular Ca2+ is able to control numerous cellular responses through complex
      spatial and temporal organization. For the effective handling of intracellular
      Ca2+, endoplasmic reticulum (ER) Ca2+ mobilization and plasma membrane Ca2+ entry
      have to be complemented by strategic and dynamic positioning of an energy source
      that is usually provided by mitochondrial ATP production. Mitochondria also
      participate in the transport of Ca2+. Mitochondria are dynamically distributed in
      cells and utilize cytoskeletal tracks and motor proteins for their movements.
      Recent studies have reported that Ca2+ inhibits mitochondrial motility providing
      a mechanism to retain mitochondria at Ca2+ signalling sites. Here we discuss the
      control of the mitochondrial distribution by cell signalling mechanisms, the
      spatial relationship among individual mitochondria and ER domains, and the
      possible implications of mitochondrial movements in the Ca(2+)-dependent cell
      survival and cell death mechanisms.

PMID- 18074635
TI  - Endoplasmic reticulum/mitochondria calcium cross-talk.
AB  - The interaction of mitochondria with the endoplasmic reticulum (ER) Ca2+ store
      plays a key role in allowing these organelles to rapidly and effectively respond
      to cellular Ca2+ signals. In this contribution, we will briefly discuss: (i) old
      and new concepts of mitochondrial Ca2+ homeostasis; (ii) the relationship between
      mitochondrial 3D structure and Ca2+ homeostasis; (iii) the modulation by
      cytoplasmic signalling pathways; and (iv) new data suggesting that mitochondria
      and ER Ca2+ channels are assembled in a macromolecular complex in which the
      inositol-1,4,5-trisphosphate receptor directly stimulates the mitochondrial Ca2+
      uptake machinery.

PMID- 18074636
TI  - Mitochondrial ion channels in cardiac function and dysfunction.
AB  - The study of mitochondrial physiology continues to provide new and surprising
      insights into how this organelle participates in the integration of cellular
      activities, far beyond the traditional view of the mitochondrion in energy
      transduction. Emerging evidence indicates that mitochondria are a centre of
      organization of numerous signalling pathways and are a cellular target that
      undergoes vast modification during both the acute and chronic phases of disease
      development and ageing. In this context, it is also important to understand the
      spatial and temporal organization of mitochondrial function and how this might
      influence the cell's response to stress. Here, we present evidence supporting the
      hypothesis that mitochondria from heart cells act as a network of coupled
      oscillators, capable of producing frequency- and/or amplitude-encoded reactive
      oxygen species (ROS) signals under physiological conditions. This intrinsic
      property of the mitochondria can lead to a mitochondrial 'critical' state, i.e.
      an emergent macroscopic response manifested as complete collapse or synchronized
      oscillation in the mitochondrial network under stress. The large amplitude
      depolarizations of deltapsi(m) and bursts of ROS have widespread effects on all
      subsystems of the cell including energy-sensitive ion channels in the plasma
      membrane, producing an effect that scales to cause organ level electrical and
      contractile dysfunction. Mitochondrial ion channels appear to play a key role in
      the mechanism of this non-linear network phenomenon and hence are an important
      target for potential therapeutic intervention.

PMID- 18074637
TI  - The mitochondrial permeability transition pore.
AB  - The mitochondrial permeability transition pore (PTP) is a high conductance
      channel of the inner membrane whose opening leads to an increase of permeability
      to solutes with molecular masses up to about 1500Da, the 'permeability
      transition'. This potentially catastrophic event has long been known, yet the
      molecular bases for its occurrence remain unsolved despite its established
      importance in several in vivo models of pathology. Recent studies based on
      inactivation of genes encoding putative pore components (such as the adenine
      nucleotide translocators and the voltage-dependent anion channel) have raised
      major questions about the involvement of these proteins in PTP formation, yet
      they have conclusively demonstrated the role of matrix cyclophilin D as the
      mitochondrial receptor for the desensitizing effects of cyclosporin A. While the
      nature of the components forming the PTP remains controversial, the
      identification of novel inhibitors that can be used as affinity labels is
      offering new perspectives towards the molecular definition of the PTP.

PMID- 18074638
TI  - Mechanisms of mitochondrial outer membrane permeabilization.
AB  - In response to many apoptotic stimuli, Bcl-2 family pro-apoptotic members, such
      as Bax and Bak, are activated. This results in their oligomerization,
      permeabilization of the outer mitochondrial membrane, and release of many
      proteins that are normally confined in the mitochondrial inter-membrane space.
      Among these proteins are cytochrome c, Smac/DIABLO, OMI/HtrA2, AIF and
      endonuclease G. Mitochondrial outer membrane permeabilization (MOMP) is also
      associated with fragmentation of the mitochondrial network. The mechanisms that
      lead to the oligomerization of proapoptotic members of the Bcl-2 family and to
      MOMP are still unclear and the role of mitochondrial fission in these events
      remains elusive.

PMID- 18074639
TI  - Mitochondria and neurodegeneration.
AB  - There is increasing evidence linking mitochondrial dysfunction to
      neurodegenerative diseases. Mitochondria are critical regulators of cell death, a
      key feature of neurodegeneration. Mutations in mitochondrial DNA and oxidative
      stress both contribute to ageing, which is the greatest risk factor for
      neurodegenerative diseases. This is the case in Alzheimer's disease, in which
      there is evidence that both beta-amyloid and the amyloid precursor protein may
      directly interact with mitochondria, leading to increased free radical
      production. In the case of Huntington's disease (HD), recent evidence suggests
      that the coactivator PGC1alpha, a key regulator of mitochondrial biogenesis in
      respiration, is down-regulated in patients with HD and in several animal models
      of this neurodegenerative disorder. In Parkinson's disease, the autosomal
      recessive genes parkin, DJ1 and PINK1 are all linked to either oxidative stress
      or mitochondrial dysfunction. In amyotrophic lateral sclerosis, there is strong
      evidence that mutant superoxide dismutase directly interacts with the outer
      mitochondrial membrane as well as the intermembrane space and matrix. Therefore,
      an impressive number of disease specific proteins interact with mitochondria.
      Therapies that target basic mitochondrial processes such as energy metabolism in
      free radical generation, or specific interactions of disease-related protein with
      mitochondria, hold great promise.

PMID- 18074640
TI  - Mitochondrial dysfunction in mammalian ageing.
AB  - Ageing is likely a multifactorial process caused by accumulated damage to a
      variety of cellular components. Increasing age in mammals correlates with
      increased levels of mitochondrial DNA (mtDNA) mutations and deteriorating
      respiratory chain function. Mosaic respiratory chain deficiency in a subset of
      cells in various tissues, such as heart, skeletal muscle, colonic crypts and
      neurons, is typically found in aged humans. Experimental evidence in the mouse
      has linked increased levels of somatic mtDNA mutations to a variety of ageing
      phenotypes, such as osteoporosis, hair loss, greying of the hair, weight
      reduction and decreased fertility. It has been known for a long time that
      respiratory chain-deficient cells are more prone to undergo apoptosis and
      increased cell loss is therefore likely of importance in age-associated
      mitochondrial dysfunction. There is a tendency to automatically link
      mitochondrial dysfunction to increased production of reactive oxygen species
      (ROS). However, the experimental support for this concept is rather weak. Mouse
      models with respiratory chain deficiency induced by tissue-specific mtDNA
      depletion or by massive increase of point mutations in mtDNA have very minor or
      no increase of oxidative stress. Future studies are needed to address the
      relative importance of mitochondrial dysfunction and ROS in mammalian ageing.

PMID- 18074641
TI  - Mitochondrial mutations: genotype to phenotype.
AB  - Diseases associated with defects of the mitochondrial respiratory chain fall into
      four major categories: (1) those due to mutations in respiratory chain subunits;
      (2) those due to mutations that affect respiratory chain assembly; (3) those due
      to mutations that affect respiratory chain function indirectly, either via
      alterations in the translation of mtDNA-encoded polypeptides or via alterations
      in mtDNA integrity; and (4) those due to mutations in nDNA that affect organellar
      morphology and mobility, in which defects in respiratory chain function can be
      considered to be 'collateral damage'. All four categories will be discussed.

PMID- 18074642
TI  - AIDS wins this round.

PMID- 18074643
TI  - The gender conundrum.

PMID- 18074644
TI  - Congress's bad drug habit.

PMID- 18074645
TI  - Where there's a bill, there's...a way. HCA units are handling bill collecting,
      other services for providers, while Tenet considers getting a piece of the
      action.
AB  - Hospitals are just not in the business of collecting money," says Suzanne
      Lestina, left, of the Healthcare Financial Management Association. "It's not
      their expertise." To tackle that problem, HCA-by way of a subsidiary-is now
      selling itself as a provider of those collection services. While it's too early
      to call this a trend, other organizations say they have pondered employing
      similar strategies.

PMID- 18074647
TI  - ACHE sees dues revenue fall. Revamped membership structure cited for decrease
      shown in Form 9901.

PMID- 18074648
TI  - AHIP's profits down in '06.

PMID- 18074649
TI  - Pennsylvania pacts. Catholic Health East agrees to sell pair of hospitals.

PMID- 18074650
TI  - To the insiders go the spoils. Policy wonks, execs, researchers grow rich from a
      system in need of repair.

PMID- 18074651
TI  - Transparent challenges. Leaders see value in reporting of price, quality data,
      but effects may be marginal.

PMID- 18074652
TI  - Look who's buying retail. Hospitals, health systems, and even physician groups
      are getting involved in the latest wave of 'convenient-care' clinics.

PMID- 18074653
TI  - Consumer-driven, at slow speed. As healthcare costs rise, plans may gain
      traction.

PMID- 18074654
TI  - Second chance. Docs, not-for-profit join forces for Ind. hospital.

PMID- 18074656
TI  - Threats to your genetic privacy.

PMID- 18074655
TI  - A threat to both mom and her baby. Gestational diabetes is on the rise, and
      experts are worried.

PMID- 18074657
TI  - GM's get-well plan. It wants to shift retiree health care to a UAW trust, in what
      could be a template for underfunded states and cites.

PMID- 18074658
TI  - The caffeine habit. Time was, you got your lift from a cup of joe. Now more and
      more products come with a kick.

PMID- 18074659
TI  - What makes us moral.

PMID- 18074660
TI  - The year in medicine from A to Z.

PMID- 18074661
TI  - Facial yoga.

PMID- 18074662
TI  - Objective assessment of temporal bone drilling skills.
AB  - OBJECTIVES: There is great interest in training surgeons in the technical aspects
      of their craft through simulation and laboratory-based exercises. However, there
      are as yet only a few objective tools to assess technical performance in a
      laboratory setting. This study assesses three potential objective assessment
      tools for a traditional otolaryngology laboratory exercise, temporal bone
      drilling. METHODS: We performed a validation study in an academic training
      program. Nineteen otolaryngology residents performed a cortical mastoidectomy on
      a cadaveric temporal bone. The participants were divided into two groups,
      experienced and novice, based on previous temporal bone drilling experience.
      Performance was rated by two independent, blinded experts using four different
      assessments, the Global Rating Scale (GRS), the Task-Based Checklist (TBC), the
      final product analysis (FPA), and expert opinion (EO). RESULTS: The interrater
      reliability for all four assessments was good. Two potential objective
      assessments, the GRS and the TBC, and the traditional assessment tool of EO,
      correlated with trainee experience. The FPA, however, did not correlate with
      trainee experience. A logistic regression analysis of all assessments showed that
      the TBC correlates with EO. CONCLUSIONS: This study validates EO, the GRS, and
      the TBC as measures of temporal bone drilling performance. Of these measures, the
      TBC correlates best with EO according to logistic regression and can be reliably
      used as an objective assessment of temporal bone drilling.

PMID- 18074663
TI  - Prediction of difficult laryngoscopy: does obesity play a role?
AB  - OBJECTIVES: This study was intended to 1) identify preoperative predictors of
      difficult laryngoscopy and 2) determine the role of obesity in difficulty of
      obtaining adequate laryngeal exposure. METHODS: A prospective study was
      undertaken of 63 patients who were undergoing elective direct laryngoscopy.
      Thirty-six patients met the obesity criteria (body mass index of at least 30
      kg/m2). Measurements of height, weight, and neck circumference and Mallampati and
      Cormack-Lehane scores were obtained. The ease of laryngeal exposure was recorded
      by the attending surgeon on a visual analog scale (VAS; 1 to 10). Difficult
      laryngeal exposure (DLE) was defined as a VAS score of at least 3. The candidate
      morphological predictors were investigated. RESULTS: Obesity and Mallampati score
      were found to be predictors of DLE (p < .001). The VAS score was positively
      correlated with body mass index (p = .007), weight (p = .05), Mallampati score (p
      < .001), and Cormack-Lehane score (p < .001). Among obese patients, the VAS score
      was correlated with the Cormack-Lehane score (p = .01), whereas in nonobese
      patients the VAS score showed a significant association with both the Mallampati
      (p = .02) and Cormack-Lehane (p = .01) scores. CONCLUSIONS: Obese patients and
      those with a Mallampati score of at least 2 posed a significantly higher risk of
      DLE. Preoperative identification of a potentially difficult airway may aid
      surgical planning and allow more effective communication with a collaborating
      anesthesiologist.

PMID- 18074664
TI  - Impact of treatment of gastroesophageal reflux on obstructive sleep apnea
      hypopnea syndrome.
AB  - OBJECTIVES: We test the hypothesis that treatment of gastroesophageal reflux
      disease (GERD) can improve obstructive sleep apnea-hypopnea syndrome (OSAHS).
      METHODS: One hundred forty-six patients with OSAHS underwent a complete history
      taking, physical examination, and laboratory testing, including questions related
      to GERD symptoms. Full-night attended polysomnography, 24-hour wireless pH study
      at the upper esophagus, snoring level evaluation, Epworth Sleepiness Scale, and
      quality-of-life surveys were completed for each patient. Patients who tested
      positive for GERD were treated with esomeprazole magnesium 40 mg once daily for 2
      to 12 months. The 24-hour pH study was repeated, and those patients with
      elimination of GERD were reevaluated by polysomnography, snoring level
      evaluation, Epworth Sleepiness Scale, quality-of-life surveys, and subjective
      data collection. RESULTS: Forty-one patients completed single-dose treatment with
      esomeprazole, but the repeat 24-hour pH study showed that 9 patients had
      persistent GERD. In the 29 patients who completed phase 2 with normal pH study
      findings, the snoring level decreased from 9.7 +/- 0.5 to 7.9 +/- 1.3 (p <
      .0001), the Epworth Sleepiness Scale score decreased from 14.2 +/- 2.5 to 11.1 +/
      2.4 (p < .0001), the apnea-hypopnea index decreased from 37.9 +/- 19.1 to 28.8
      +/- 11.5 (p = .006), and the minimum saturation of oxygen increased from 84.1% +/
      7.8% to 86.9% +/- 5.0% (p = .055). CONCLUSIONS: Treatment of GERD had a
      significant impact on the reduction of the apnea-hypopnea index, snoring, and
      daytime sleepiness. Elimination of GERD should be part of a comprehensive
      treatment plan for patients with OSAHS.

PMID- 18074665
TI  - Auditory Skills Checklist: clinical tool for monitoring functional auditory skill
      development in young children with cochlear implants.
AB  - OBJECTIVES: The Auditory Skills Checklist (ASC) was developed to address the need
      for tools to evaluate functional auditory skill progress in very young children
      with sensorineural hearing loss. We describe the development, validation, and
      utility of the ASC for use in young children with cochlear implants. METHODS:
      Using the ASC, we measured auditory skills in 37 subjects who received cochlear
      implants at no more than 36 months of age. Repeated measures analysis was
      conducted to determine expected auditory skill development after implantation.
      Interrater reliability was tested on a small subset. The ASC was compared to the
      Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) to determine its
      validity in measuring functional auditory skills. RESULTS: The ASC had excellent
      internal consistency (Cronbach's alpha, 0.98) and interrater reliability
      (intraclass correlation coefficient, 0.99), and was highly correlated with the IT
      MAIS (r = 0.90). According to the repeated measures analysis, children who
      received a cochlear implant at 36 months of age or earlier were expected to
      increase their ASC score by 8 points every 3 months (beta coefficient, 8.3; p <
      .001). CONCLUSIONS: The ASC is a clinically relevant and easily administered tool
      for assessing the functional auditory skills of young children with a cochlear
      implant. By assessing auditory skill development over time with the ASC, we can
      better realize expectations for a particular child based on his or her age,
      hearing loss level, and management strategies in place.

PMID- 18074666
TI  - Drilling simulated temporal bones with left-handed tools: a left-hander's right?
AB  - OBJECTIVES: Left-handed trainees can be at a disadvantage in the surgical
      environment because of a right-handed bias. The effectiveness of teaching left
      handed trainees to use an otologic drill designed for their dominant hand versus
      the conventional right-handed drill was examined. METHODS: Novice medical
      students were recruited from the university community. Twenty-four subjects were
      left-handed, and 12 were right-handed. Eight left-handed surgeons also
      participated. A randomized controlled trial was conducted to compare the
      performance of left-handed trainees using novel left-handed drills to that of
      left-handed trainees using right-handed tools and to that of right-handed
      trainees using right-handed tools. The evaluation consisted of 3 phases: pretest,
      skill acquisition, and 2 post-tests. The measurement tools included expert
      assessment of performance, and subjective and objective final product analyses.
      RESULTS: An initial construct validity phase was conducted in which validity of
      the assessment tools was ensured. Both the left-handers using left-handed tools
      and the right-handers using right-handed tools significantly outperformed the
      left-handers using right-handed tools at pretest, immediate posttest, and delayed
      posttest. All participants improved their performance as a function of practice.
      CONCLUSIONS: The left-handed trainees learned bone drilling better with tools
      designed for the left hand. These tools may be incorporated into residency
      training programs for the development of surgical technical skills. Future
      studies should assess skill transfer between the left-handed and right-handed
      drills.

PMID- 18074667
TI  - Noninvasive assessment of benign lesions of vocal folds by means of
      ultrasonography.
AB  - OBJECTIVES: Although ultrasonography (US) has been widely used in various parts
      of the body, its application in laryngeal examination has been limited. Our
      objective was to evaluate the significance of US examination in benign lesions of
      the vocal folds. METHODS: Ultrasonographic examination of the vocal folds was
      performed in 14 patients in whom benign lesions of the vocal folds had been
      diagnosed by videolaryngoscopy and microlaryngoscopy. Microlaryngoscopic surgery
      was performed after US examination. Each lesion was analyzed for the following US
      features: shape, size, and echotexture (echogenicity and homogeneity). RESULTS:
      In total, 16 lesions were diagnosed in 14 patients by means of videolaryngoscopy
      and microlaryngoscopy. Ultrasonographic examination was capable of diagnosing 14
      of the 16 lesions (87.25%). Ultrasonography mainly helped in the diagnosis of
      sessile polyps, nodules, and leukoplakia that were larger than 2 mm. The lesions
      were linear hyperechoic, heterogeneous hyperechoic, hypoechoic, and isoechoic if
      they were leukoplakia, nodules, hemorrhagic polyps, and other polypoid lesions,
      respectively. The results are better if the diagnosis follows the corresponding
      US echotexture pattern rather than videolaryngoscopy and microlaryngoscopy.
      CONCLUSIONS: Laryngeal US examination appears to be a useful diagnostic tool for
      supplementing microlaryngoscopy in the assessment of benign lesions of vocal
      folds. In contrast to these currently used imaging techniques, anesthesia is not
      necessary in laryngeal US examination. In addition, US is noninvasive, painless,
      and much less expensive than the other techniques.

PMID- 18074668
TI  - Treatment of early-stage glottic cancer by transoral laser resection.
AB  - OBJECTIVES: We reviewed outcomes of treatment of early glottic carcinoma by
      transoral laser resection. METHODS: We performed a retrospective study of tumor
      stage, type of cordectomy (European Laryngological Society), resection margins,
      local control, and laryngeal preservation. RESULTS: Of 142 patients treated with
      curative intent, 79 (92% male; average age, 63 years) were retained for this
      study, on the basis of availability of information regarding resection margins,
      the absence of adjuvant radiotherapy, and followup of at least 2 years. The
      tumors were classified pTis (n = 21), pT1a (n = 51), or pT1b (n = 7) and were
      treated by cordectomy types I (23%), II (30%), III (27%), IV (6%), and V (14%).
      The average follow-up was 56 months (range, 24 to 150 months). The overall 5-year
      actuarial recurrence-free survival rate was 89%, and the 5-year actuarial disease
      specific survival rate was 97.3%. There were 11 local recurrences (14%); 7 were
      treated by another laser resection, 1 by radiotherapy, 1 by supracricoid partial
      laryngectomy, and 2 by total laryngectomy. The overall rate of final local
      control with the laser alone was 100% for patients with initially positive
      margins, 95% for those with initially suspicious margins, and 94% for those with
      free margins. The overall rate of organ preservation was 100% for patients with
      positive or suspicious margins and 96% for those with free margins. Margin status
      (p = .39), cordectomy type (p = .67), and anterior commissure involvement (p =
      .16) were not statistically related to recurrence (Kaplan-Meier calculations with
      nonparametric univariate analysis). The recurrence rate was significantly higher
      for T1b tumors, however (p = .001). CONCLUSIONS: Laser microresection provides
      high rates of local control and organ preservation for early glottic cancer.
      Positive or suspicious margins were not related to recurrence, nor was anterior
      commissure involvement. This study implies that suspicious margins can be managed
      with a "watch-and-wait" attitude. Re-treatment with laser, external partial
      laryngectomy, and radiotherapy remain therapeutic options for recurrences.

PMID- 18074669
TI  - Dysphagia after chemoradiation: analysis by modified barium swallow.
AB  - OBJECTIVES: We sought to describe the findings of modified barium swallow study
      after chemoradiation in patients with head and neck cancer and to correlate these
      findings with clinical variables, including gastrostomy tube dependence and
      clinical pneumonia. METHODS: We retrospectively reviewed 49 patients at a
      tertiary care center who underwent modified barium swallow study for dysphagia
      after chemoradiation. RESULTS: Patients with nonlaryngeal lesions had increased
      cricopharyngeal impairment (27.8% versus 0.0%; p = .04). Patients who underwent
      concomitant chemotherapy had increased epiglottic changes relative to those who
      had radiotherapy alone (66.7% versus 30.8%; p = .05). Clinical pneumonia
      developed in 31.9% of the patients, and 79.6% required gastrostomy tube placement
      for a mean duration of 18.1 months. CONCLUSIONS: Chemoradiation effects
      deglutition at multiple levels. A large percentage of patients will develop
      pneumonia and feeding tube dependence. This study is among the largest to
      correlate the results of modified barium swallow studies to clinical variables in
      this patient population. This study highlights the significant incidence of
      gastrostomy tube dependence and pneumonia in these patients.

PMID- 18074670
TI  - Prevalence of upper airway tumors and cysts among patients who snore.
AB  - OBJECTIVES: Sleep specialists usually do not pay much attention to the upper
      airway in patients who snore, because they can make the diagnosis of sleep
      disordered breathing without performing nasopharyngeal endoscopy if they have the
      Epworth Sleepiness Scale scores and the results of polysomnography. The purpose
      of this study was to determine the prevalence of benign and malignant tumors and
      cysts in the upper airway in patients who snore. METHODS: A retrospective
      multicenter trial was performed in 4 sleep laboratories. Adult male and female
      patients whose chief complaint on their first visit was witnessed snoring were
      enrolled in this study. All of the patients were evaluated by otolaryngologists
      using nasopharyngeal endoscopy to detect organic diseases in the upper airway.
      RESULTS: Among 2,923 patients, 2 patients had malignant tumors, 5 had benign
      tumors, and 2 had cysts in the upper airway. The prevalence of upper airway
      benign and malignant tumors and cysts among adult male and female patients was
      0.24%. CONCLUSIONS: Routine detailed nasopharyngeal endoscopy should be carried
      out in each institution so as not to overlook organic diseases in the upper
      airway among patients who snore.

PMID- 18074671
TI  - Side population cells in the human vocal fold.
AB  - OBJECTIVES: The regenerative processes of the vocal fold, or the existence of
      stem cells in the folds, are unknown. Side population (SP) cells are defined as
      cells that have the ability to exclude the DNA binding dye, Hoechst 33342. They
      are regarded as a cell population enriched with stem cells and can be isolated
      from non-SP cells by a fluorescence-activated cell sorter. This study was
      designed to determine whether SP cells exist in the human vocal fold, as a first
      step in elucidating the regenerative mechanisms of the vocal fold. METHODS: Seven
      human excised larynges were used in this study. Two were used for fluorescence
      activated cell sorter analysis, and 5 were subjected to immunohistochemical
      analysis with antibodies against an adenosine triphosphate binding cassette
      transporter family member, ABCG2, which is expressed in SP cells. RESULTS: The
      number of SP cells in the human vocal fold was about 0.2% of the total number of
      cells. ABCG2-positive cells were identified in both the epithelium and
      subepithelial tissue throughout the entire vocal fold. CONCLUSIONS: This
      preliminary study demonstrated the existence of SP cells in the human vocal fold.
      Further studies are warranted to clarify how these cells work in the vocal fold,
      particularly in the regenerative process.

PMID- 18074672
TI  - Thermal damage during thulium laser dissection of laryngeal soft tissue is
      reduced with air cooling: ex vivo calf model study.
AB  - OBJECTIVES: The 2-microm-wavelength thulium laser has recently been shown to be
      an effective cutting instrument in endolaryngeal surgery, although there is
      increased thermal trauma as compared with the carbon dioxide laser. This study
      investigated temperature changes and thermal trauma during thulium laser
      dissection of laryngeal tissue, with and without air cooling, in an ex vivo
      model. METHODS: A continuous-wave thulium laser (400-microm fiber, 4-W continuous
      power, 4-second duration) was used to incise 10 calf vocal folds. Paired cooled
      and uncooled cuts were made in each fold with a dermatologic cooling device. A
      thermistor inserted into the glottic subepithelium was used to measure tissue
      temperatures. Thermal damage was analyzed histologically by measuring the depth
      of the zone of lactate dehydrogenase inactivation surrounding the mucosal
      incision. RESULTS: The initial vocal fold temperature averaged 24.3 degrees C
      without cooling and 4.4 degrees C with cooling. The peak temperature during
      cutting averaged 59.1 degrees C without cooling and 28.0 degrees C with cooling.
      The thermal damage zone surrounding the cooled incisions was approximately 27%
      less than that surrounding the uncooled incisions. CONCLUSIONS: Air cooling can
      reduce the extent of thermal trauma associated with thulium laser surgery of the
      vocal folds, and the high-temperature plume generated during laser cutting is
      effectively cleared.

PMID- 18074673
TI  - Dysphagia in the elderly: preliminary evidence of prevalence, risk factors, and
      socioemotional effects.
AB  - OBJECTIVES: Epidemiological studies of dysphagia in the elderly are rare. A non
      treatment-seeking, elderly cohort was surveyed to provide preliminary evidence
      regarding the prevalence, risks, and socioemotional effects of swallowing
      disorders. METHODS: Using a prospective, cross-sectional survey design, we
      interviewed 117 seniors living independently in Utah and Kentucky (39 men and 78
      women; mean age, 76.1 years; SD, 8.5 years; range, 65 to 94 years) regarding 4
      primary areas related to swallowing disorders: lifetime and current prevalence,
      symptoms and signs, risk and protective factors, and socioemotional consequences.
      RESULTS: The lifetime prevalence of a swallowing disorder was 38%, and 33% of the
      participants reported a current problem. Most seniors with dysphagia described a
      sudden onset with chronic problems that had persisted for at least 4 weeks.
      Stepwise logistic regression identified 3 primary symptoms uniquely associated
      with a history of swallowing disorders: taking a longer time to eat (odds ratio
      [OR], 9.5; 95% confidence interval [CI], 2.3 to 40.2); coughing, throat clearing,
      or choking before, during, or after eating (OR, 3.4; 95% CI, 1.1 to 10.2); and a
      sensation of food stuck in the throat (OR, 5.2; 95% CI, 1.8 to 10.0). Stroke (p =
      .02), esophageal reflux (p = .003), chronic obstructive pulmonary disease (p =
      .05), and chronic pain (p = .03) were medical conditions associated with a
      history of dysphagia. Furthermore, dysphagia produced numerous adverse
      socioemotional effects. CONCLUSIONS: This study provides preliminary evidence to
      suggest that chronic swallowing disorders are common among the elderly, and
      highlights the need for larger epidemiological studies of these disorders.

PMID- 18074674
TI  - Ex vivo perfused larynx model of phonation: preliminary study.
AB  - OBJECTIVES: Although excised laryngeal models and physical models of the larynx
      are important in the study of laryngeal dynamics, they cannot be used to study
      the influence of neuromuscular contraction on vocal fold vibration, especially
      with regard to the thyroarytenoid muscle. Our aim was to develop an ex vivo
      larynx model of phonation, and combine the benefits of the in vivo and excised
      laryngeal models to the ex vivo situation. METHODS: Three canine larynges were
      surgically removed and perfused ex vivo with modified Krebs-Henseleit reperfusion
      solution. The laryngeal nerves were stimulated, and an assessment of
      neuromuscular viability, phonation, and vocal fold vibration was made. RESULTS:
      Neuromuscular stimulation, phonation, and experimental manipulation were possible
      for several hours after the onset of ex vivo perfusion. Repeatable periodic
      phonation in short bursts was achieved. Perfusion appears critical to maintain ex
      vivo viability, as adductory force was almost immediately lost upon cessation of
      ex vivo perfusion. CONCLUSIONS: The ex vivo larynx model has the potential to
      facilitate the measurement of glottal variables in a neuromuscularly correct
      model. We propose that the further development of this laryngeal model may be
      useful in the study of laryngeal dynamics, particularly when invasive
      measurements, such as that of glottal exit flow, are required.

PMID- 18074675
TI  - Functional evidence for a nasopharyngeal carcinoma-related gene BCAT1 located at
      12p12.
AB  - Nasopharyngeal carcinoma (NPC) is a malignancy that is prevalent among
      populations from Southeast Asia. The carcinogenesis of NPC is thought to be a
      multistep process involving several genetic changes. Our previous study based on
      distance and branching-tree models for NPC carcinogenesis indicated +12p11-p12
      was an early event and should play an important role in NPC development. To
      understand the role of +12p11-p12 as the tree model predicted and evaluate which
      gene located at 12p11-p12 might be involved in NPC development, semiquantitative
      RT-PCR was applied to examine the expression status of 18 genes selected from
      12p11-p12 in 36 NPC and 8 normal nasopharynx (NP) biopsies. The results revealed
      that BCAT1, KCNJ8, PTX1, and KRAS2 genes were overexpressed in NPC tissues and
      BCAT1 was of particular interest based on its function reported in other tumors.
      To further elucidate the function of BCAT1 gene in NPC, BCAT1 expression was
      specifically suppressed in 5-8F NPC cell line by RNA interference (RNAi),
      confirmed by RT-PCR and Western blotting. As expected, the depletion of BCAT1
      could effectively block the proliferation of NPC cells. The BCAT1 identified in
      the amplified 12p11-p12 region may play a certain role in NPC development.

PMID- 18074676
TI  - Antitumor activity of mannan-methotrexate conjugate in vitro and in vivo.
AB  - Conjugation of anticancer drugs with different carriers has been extensively
      studied recently as a potential method of obtaining improved drug forms. The
      conjugation often results in the increase of the therapeutic effect, alteration
      of a toxicity profile, and/or selective targeting of therapeutic agent to the
      tissue of interest. We have synthesized mannan-methotrexate conjugate by means of
      methotrexate anhydride and studied its antitumor properties both in vitro and in
      vivo in comparison with free methotrexate. Mannan-methotrexate conjugate showed
      significantly improved antitumor activity compared to free methotrexate in the
      model of P388 mouse leukemia disseminated in the peritoneal cavity treated with
      intraperitoneally injected chemotherapy. Conversely, the antitumor effects of
      free methotrexate and mannan-methotrexate conjugate were comparable when leukemia
      was implanted subcutaneously and chemotherapy agents were administered
      intravenously. These results suggest that mannan-methotrexate conjugate should be
      further investigated as a potential therapeutic agent for intraperitoneally
      disseminated tumors.

PMID- 18074677
TI  - The role of GSTM1 and GSTT1 polymorphisms in head and neck cancer risk.
AB  - Head and neck cancer (HNC) is a serious health problem worldwide and tobacco
      smoke is a main causative factor for this malignancy. Interindividual genetic
      differences in enzymes involved in the metabolism of tobacco smoke carcinogens
      are one of the most important risk factors in the development of HNC. GSTM1 and
      GSTT1 enzymes participate in detoxifying of tobacco smoke carcinogens and have
      deletion polymorphisms. We performed a case control study to investigate a
      possible association between GSTM1 and GSTT1 variants and HNC risk. A total of 98
      HNC cases, all of which were squamous cell carcinoma, and 120 healthy controls
      were investigated. GSTM1 and GSTT1 polymorphisms were genotyped using PCR. There
      was a significant association between HNC and GSTM1-null genotype (adjusted OR:
      2.36, 95% CI: 1.303-4.26, p = 0.005). The frequency overall of GSTT1-null
      genotypes was not significant in HNC patients compared with that of GSTT1
      positive genotypes (adjusted OR: 1.16, 95% CI: 0.563-2.397, p = 0.686). No
      combined effect was observed for GSTM1 and GSTT1 genotypes. When data were
      stratified by smoking status, cases having GSTM1-null genotype who were smokers
      conferred the highest risk (adjusted OR: 4.06, 95% CI: 1.3-12.63). Thus, our
      results suggest that GSTM1 polymorphism may significantly increase the risk of
      HNC and there is an additive interaction between GSTM1-null genotype and smoking
      on HNC risk.

PMID- 18074678
TI  - Loss of Hugl-1 expression associates with lymph node metastasis in endometrial
      cancer.
AB  - Mutation of neoplastic tumor suppressor genes, scribble, discs large, and lethal
      giant larvae (lgl), causes disruption of cell polarity and overproliferation of
      Drosophila epithelial cells and neuroblasts. Reduced expression of human
      homologue of lgl, Hugl-1, has been reported to be involved in development and
      progression of human colon cancer and malignant melanoma. To explore the
      association between Hugl-1 expression and clinical character in endometrial
      cancer, we examined the expression of Hugl-1 in primary endometrial cancer
      tissues. The expression of Hugl-1 mRNA in 86 primary endometrial cancer tissues
      was examined using semiquantitative reverse transcription polymerase chain
      reaction (RT-PCR). All samples were categorized into two groups: Hugl-1 positive
      and Hugl-1 negative. Clinical data of each group were analyzed by Fisher's exact
      probability test and survival rates of each group were compared by Kaplan-Meier
      method and Log-rank test. Loss of Hugl-1 expression had correlation with the
      higher incidence of lymph node metastasis, but not to the patient's age at onset,
      distant metastasis, clinical stage, lymph or venous vessel invasion, or
      histopathological grade of differentiation. The Hugl-1-positive group had poorer
      prognosis compared with the Hugl-1-negative group. These results indicate that
      loss of Hugl-1 expression in endometrial cancer may contribute to lymph node
      metastasis and it can be a factor of poor prognosis.

PMID- 18074679
TI  - CYP1A1 Msp1 T/C polymorphism in esophageal cancer: no association and risk
      modulation.
AB  - Phase I enzyme CYP1A1 metabolizes environmental carcinogens and a Msp1 T/C
      functional polymorphism in 3'UTR in its gene has been reported to influence the
      inducibilty of the enzyme. There are controversies regarding association of the
      polymorphism with risk of esophageal cancer in Chinese and Caucasian populations.
      Moreover, no study has been done in Indian populations. The present study was
      aimed to explore the associations of CYP1A1 3'UTR polymorphism with clinical
      phenotypes and environmental interaction in esophageal cancer from North Indian
      population. A total of age- and gender-matched 161 cases and 201 healthy controls
      were used to genotype the CYP1A1 3'UTR polymorphism by PCR-EFLP methodology. None
      of the CYP1A1 genotypes and alleles was significantly associated with risk of
      esophageal cancer, even after adjusting for age and sex. After stratifying the
      genotypes according to disease characteristics such as tumor histology, location,
      and lymph nodes, individuals with TT genotype were at high risk for developing
      tumor in the upper third location (OR: 2.2, 95% CI: 0.81-6.2, p = 0.11).
      Interaction of tobacco usage (smoking or nonsmoking) and presence of occupational
      exposure in esophageal cancer patients did not show significant increase in
      cancer risk with CYP1A1 genotypes. However, in patients with alcohol habits, TT
      genotype showed a higher risk, which was not significant (OR: 2.5, 95% CI: 0.61
      10.6, p = 0.19). In conclusion, CYP1A1 genotype did not influence the
      susceptibility of developing esophageal cancer. The presence of variant CYP1A1
      genotypes together with environmental exposures also did not modulate the cancer
      risk.

PMID- 18074680
TI  - Serum levels of VEGF-C, VEGF-D, and sVEGF-R2 in patients with lung cancer during
      chemotherapy.
AB  - The aim of this study was to assess serum levels of vascular endothelial growth
      factor C and D (VEGF-C, VEGF-D) and soluble VEGF receptor 2 (sVEGFR-2) in
      patients with lung cancer during chemotherapy. The study included 80 patients (64
      men and 16 women; mean age 61.1) diagnosed histologically with lung cancer. Forty
      four (55%) had non-small cell lung cancer (NSCLC) and 36 (45%) had small cell
      lung cancer (SCLC). Squamous cell carcinoma was established in 56% (25 patients)
      of all patients with NSCLC, adenocarcinoma in 20% (9 patients), and non-small
      cell lung cancer in 23% (10 patients). The control group consisted of 20 healthy
      volunteers. Peripheral blood samples were taken before and after four cycles of
      chemotherapy. VEGF-C, VEGF-D, and sVEGFR-2 levels were assessed by ELISA method.
      Serum levels of VEGF-C and VEGF-D were significantly higher in both NSCLC and
      SCLC groups in comparison with controls. VEGF-C concentration decreased after
      chemotherapy, whereas VEGF-D concentration was at the same level. No correlation
      was found between VEGF-C and VEGF-D concentrations and the effect of treatment.
      Patients with lung cancer and progression after chemotherapy (PD) had the higher
      concentration of sVEGFR-2 than patients with partial remission (PR). The levels
      of sVEGFR-2 were lower before and after treatment than in controls. No relation
      was found between VEGF-C, VEGF-D, and sVEGFR-2 concentrations and the
      histological type and staging of lung cancer. Summing up, serum concentrations of
      VEGF-C and VEGF-D were higher in patients with lung cancer both before and after
      chemotherapy than in healthy controls, whereas sVEGFR-2 concentration was lower
      than in healthy controls. An increase in concentration of sVEGFR-2 during
      chemotherapy may suggest progression of the disease. However, it requires further
      examination.

PMID- 18074681
TI  - Degenerative lumbar spinal stenosis: analysis of results in a series of 374
      patients treated with unilateral laminotomy for bilateral microdecompression.
AB  - OBJECT: Surgical decompression is the recommended treatment in patients with
      moderate to severe degenerative lumbar spinal stenosis (DLSS) in whom symptoms do
      not respond to conservative therapy. Multilevel disease, poor patient health, and
      advanced age are generally considered predictors of a poor outcome after surgery,
      essentially because of a surgical technique that has always been considered
      invasive and prone to causing postoperative instability. The authors present a
      minimally invasive surgical technique performed using a unilateral approach for
      lumbar decompression. METHODS: A retrospective study was conducted of data
      obtained in a consecutive series of 473 patients treated with unilateral
      microdecompression for DLSS over a 5-year period (2000-2004). Clinical outcome
      was measured using the Prolo Economic and Functional Scale and the visual analog
      scale (VAS). Radiological follow-up included dynamic x-ray films of the lumbar
      spine and, in some cases, computed tomography scans. RESULTS: Follow-up was
      completed in 374 (79.1%) of 473 patients--183 men and 191 women. A total of 520
      levels were decompressed: 285 patients (76.2%) presented with single-level
      stenosis, 86 (22.9%) with two-level stenosis, and three (0.9%) with three-level
      stenosis. Three hundred twenty-nine patients (87.9%) experienced a clinical
      benefit, which was defined as neurological improvement in VAS and Prolo Scale
      scores. Only three patients (0.8%) reported suffering segmental instability at a
      treated level, but none required surgical stabilization, and all were
      successfully treated conservatively. CONCLUSIONS: Evaluation of the results
      indicates that unilateral microdecompression of the lumbar spine offers a
      significant improvement for patients with DLSS, with a lower rate of
      complications.

PMID- 18074682
TI  - Spinal dumbbell tumors: an analysis of a series of 118 cases.
AB  - OBJECT: The authors analyzed a series of 118 cases of spinal dumbbell tumors to
      elucidate the feature of the tumors. METHODS: Of 674 cases of spinal cord tumors,
      the incidence of dumbbell tumors was studied. The tumors were analyzed, and the
      authors focus on the distribution of age and sex, the pathological diagnoses,
      their locations, Eden classification, and the surgical methods used. RESULTS: The
      incidence of dumbbell tumors was 18%. The mean patient age was 43 years, which
      was younger than that for all spinal cord tumors (mean 50 years). There were 11
      patients younger than 10 years of age. The rate of dumbbell tumors in the
      cervical spine was significantly higher than that of all spinal cord tumors.
      Fifteen (18%) of the 81 schwannomas were observed in the C-2 nerve root, thus
      having a higher incidence than those in the other nerve roots. In 99 cases (84%),
      the tumors were removed through a hemilaminectomy with or without a facetectomy
      and posterior fusion. Of 118 cases, 69% of the tumors were schwannomas, and
      malignant tumors were found in 10 cases (8.5%). Seven (64%) of 11 patients
      younger than 10 years of age had malignant tumors. Three patients older than 10
      years of age had malignant tumors, thus accounting for 2.8% of the 107 older
      patients. CONCLUSIONS: The incidence of dumbbell tumors was 18%, and they are not
      uncommon. Malignant dumbbell tumors were more common in children younger than 10
      years of age than in older patients.

PMID- 18074683
TI  - Basilar impression and osteogenesis imperfecta: a 21-year retrospective review of
      outcomes in 20 patients.
AB  - OBJECT: Basilar impression (BI) secondary to osteogenesis imperfecta (OI) is a
      rare but debilitating condition that is often progressive unless it is halted.
      More recently, ventral decompression surgery has been advocated for this
      condition. This study is a retrospective review of the 21-year experience of
      ventral decompression surgery and dorsal occipitocervical fixation in patients
      with BI secondary to OI and is the largest patient series reported to date.
      METHODS: Twenty patients treated between 1982 and 2003 by the senior author at
      the authors' institution were included in this study. All patients underwent
      ventral decompression surgery followed by dorsal craniocervical stabilization.
      Patients were followed up for a median of 10 years. RESULTS: There were no
      intraoperative or perioperative deaths. Postoperatively, 16 of 20 (80%) patients
      showed objective improvement or maintained their good preoperative level of
      function. After surgery, of the 15 patients admitted with Karnofsky Performance
      Scale (KPS) scores of 70% or less, 11 improved, two remained unchanged, one
      patient's condition deteriorated, and one patient died of an unrelated cause. Of
      five patients admitted with a KPS score of 80% or greater, no patient's condition
      deteriorated in the short- and midterm period, but one patient had recurrence 15
      years after surgery. At the end of follow-up, 25% of the patients had recurrence
      of brainstem compression symptoms or had died, and 15% showed no improvement
      after surgery. All of the remaining patients (60%) had sustained a long-term
      benefit from surgery. CONCLUSIONS: Aggressive ventral decompression surgery and
      dorsal stabilization for patients with BI secondary to OI can not only halt
      disease progression but can also produce a good and sustainable long-term
      functional outcome, even in those patients who present as severely symptomatic.
      Patients who presented early with minor symptoms had good long-term outcomes.

PMID- 18074684
TI  - Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and chiari
      malformation type I in patients with hereditary disorders of connective tissue.
AB  - OBJECT: Chiari malformation Type I (CM-I) is generally regarded as a disorder of
      the paraxial mesoderm. The authors report an association between CM-I and
      hereditary disorders of connective tissue (HDCT) that can present with lower
      brainstem symptoms attributable to occipitoatlantoaxial hypermobility and cranial
      settling. METHODS: The prevalence of HDCT was determined in a prospectively
      accrued cohort of 2813 patients with CM-I. All patients underwent a detailed
      medical and neuroradiological workup that included an assessment of articular
      mobility. Osseous structures composing the craniocervical junction were
      investigated morphometrically using reconstructed 3D computed tomography and
      plain x-ray images in 114 patients with HDCT/CM-I, and the results were compared
      with those obtained in patients with CM-I (55 cases) and healthy control
      individuals (55 cases). RESULTS: The diagnostic criteria for Ehlers-Danlos
      syndrome and related HDCT were met in 357 (12.7%) of the 2813 cases.
      Hereditability was generally compatible with a pattern of autosomal dominant
      transmission with variable expressivity. The diagnostic features of HDCT/CM-I
      were distinguished from those of CM-I by clinical stigmata of connective tissue
      disease, a greater female preponderance (8:1 compared with 3:1, p < 0.001), and a
      greater incidence of lower brainstem symptoms (0.41 compared with 0.11, p <
      0.001), retroodontoid pannus formation (0.71 compared with 0.11, p < 0.001), and
      hypoplasia of the oropharynx (0.44 compared with 0.02, p < 0.001). Measurements
      of the basion-dens interval, basion-atlas interval, atlas-dens interval, dens
      atlas interval, clivus-atlas angle, clivus-axis angle, and atlas-axis angle were
      the same in the supine and upright positions in healthy control individuals and
      patients with CM-I. In patients with HDCT/CM-I, there was a reduction of the
      basion-dens interval (3.6 mm, p < 0.001), an enlargement of the basion-atlas
      interval (3.0 mm, p < 0.001), and a reduction of the clivus-axis angle (10.8
      degrees, p < 0.001), clivus-atlas angle (5.8 degrees, p < 0.001), and atlas-axis
      angle (5.3 degrees, p < 0.001) on assumption of the upright position. These
      changes were reducible by cervical traction or returning to the supine position.
      CONCLUSIONS: The identification of HDCT in 357 patients with CM-I establishes an
      association between two presumably unrelated mesodermal disorders. Morphometric
      evidence in this cohort-cranial settling, posterior gliding of the occipital
      condyles, and reduction of the clivus-axis angle, clivus-atlas angle, and atlas
      axis angle in the upright position-suggests that hypermobility of the
      occipitoatlantal and atlantoaxial joints contributes to retroodontoid pannus
      formation and symptoms referable to basilar impression.

PMID- 18074685
TI  - Cervical malalignment after laminoplasty: relationship to deep extensor
      musculature of the cervical spine and neurological outcome.
AB  - OBJECT: The goal of this study was to investigate the relationship between
      preservation of the insertion of the deep extensor musculature of the cervical
      spine at C-2 and postoperative cervical alignment, especially differences between
      cases involving male and female patients, as well as the relationship between the
      loss of cervical lordosis and neurological outcome after laminoplasty. METHODS:
      The authors reviewed the records of 50 patients who underwent laminoplasty to
      elevate the C-3 lamina with repair of the deep extensor musculature (Group A) and
      31 patients who underwent laminoplasty by C-3 dome laminotomy or laminectomy
      (Group B). They compared the degree of cervical lordosis after laminoplasty with
      preoperative measurements. Neurological function at last follow-up was also
      compared with preoperative assessments. RESULTS: In Group A, the mean values for
      pre- and postoperative cervical lordosis were 14.5 and 10.9 degrees, respectively
      (p > 0.18). In female patients, however, the pre- and postoperative means were
      14.4 and 3.7 degrees, respectively (p < 0.004). In Group B, the overall means for
      pre- and postoperative cervical lordosis were 17.3 and 19.1 degrees, respectively
      (p > 0.48); the corresponding means for female patients were 15.0 and 14.1
      degrees (p > 0.83). The mean percentages of neurological recovery were 54.1% in
      Group A and 54.8% in Group B. CONCLUSIONS: Preservation of the insertion of the
      deep extensor musculature to the C-2 spinous process prevented significant
      changes in cervical alignment after laminoplasty, even among female patients.
      Neurological recovery was not affected by the loss of cervical lordosis.

PMID- 18074686
TI  - Prognostic relevance of the postoperative evolution of intramedullary spinal cord
      changes in signal intensity on magnetic resonance imaging after anterior
      decompression for cervical spondylotic myelopathy.
AB  - OBJECT: Areas of intramedullary signal intensity changes (hypointensity on T1
      weighted magnetic resonance [MR] images and hyperintensity on T2-weighted MR
      images) in patients with cervical spondylotic myelopathy (CSM) have been
      described by several investigators. The role of postoperative evolution of these
      alterations is still not well known. METHODS: A total of 47 patients underwent MR
      imaging before and at the end of the surgical procedure (intraoperative MR
      imaging [iMRI]) for cervical spine decompression and fusion using an anterior
      approach. Imaging was performed with a 1.5-tesla scanner integrated with the
      operative room (BrainSuite). Patients were followed clinically and evaluated
      using the Japanese Orthopaedic Association (JOA) and Nurick scales and also
      underwent MR imaging 3 and 6 months after surgery. RESULTS: Preoperative MR
      imaging showed an alteration (from the normal) of the intramedullary signal in 37
      (78.7%) of 47 cases. In 23 cases, signal changes were altered on both T1- and T2
      weighted images, and in 14 cases only on T2-weighted images. In 12 (52.2%) of the
      23 cases, regression of hyperintensity on T2-weighted imaging was observed
      postoperatively. In 4 (17.4%) of these 23 cases, regression of hyperintensity was
      observed during the iMRI at the end of surgery. Residual compression on
      postoperative iMRI was not detected in any patients. A nonsignificant correlation
      was observed between postoperative expansion of the transverse diameter of the
      spinal cord at the level of maximal compression and the postoperative JOA score
      and Nurick grade. A statistically significant correlation was observed between
      the surgical result and the length of a patient's clinical history. A significant
      correlation was also observed according to the preoperative presence of
      intramedullary signal alteration. The best results were found in patients without
      spinal cord changes of signal, acceptable results were observed in the presence
      of changes on T2-weighted imaging only, and the worst results were observed in
      patients with spinal cord signal changes on both Tl- and T2-weighted imaging.
      Finally, a statistically significant correlation was observed between patients
      with postoperative spinal cord signal change regression and better outcomes.
      CONCLUSIONS: Intramedullary spinal cord changes in signal intensity in patients
      with CSM can be reversible (hyperintensity on T2-weighted imaging) or
      nonreversible (hypointensity on T1-weighted imaging). The regression of areas of
      hyperintensity on T2-weighted imaging is associated with a better prognosis,
      whereas the T1-weighted hypointensity is an expression of irreversible damage
      and, therefore, the worst prognosis. The preliminary experience with this patient
      series appears to exclude a relationship between the time of signal intensity
      recovery and outcome of CSM.

PMID- 18074687
TI  - Association of methylenetetrahydrofolate reductase genetic polymorphisms with
      atlantoaxial dislocation.
AB  - OBJECT: Genetic mechanisms of atlantoaxial dislocation (AAD) have not previously
      been elucidated. The authors studied association of polymorphisms in the
      methylenetetrahydrofolate reductase (MTHFR) gene, which encodes enzymes of the
      folate pathway (implicated in causation of neural tube defects [NTDs]), in
      patients with AAD. METHODS: Molecular analysis of MTHFR polymorphisms (677C-->T,
      cytosine to thymine and, 1298A-->C, adenine to cytosine, substitutions) was
      carried out using polymerase chain reaction and restriction enzyme digestion in
      75 consecutive patients with AAD and in their reducible (nine patients, 12%) and
      irreducible (66 patients, 88%) subgroups. Controls were 60 age- and sex-matched
      patients of the same ethnicity. Comparisons of genotype and allele frequencies
      were performed using a chi-square test (with significance at p < 0.05). RESULTS:
      The CT genotype frequency of MTHFR 677C-->T polymorphism was significantly
      increased in the full group of patients with AAD (odds ratio [OR] 3.00, 95%
      confidence interval [CI] 1.28-7.14, p = 0.005) as well as in the irreducible
      subgroup (OR 2.81, 95% CI 1.17-6.86, p = 0.01). The frequency of T alleles was
      also higher in the AAD group (25.3%) than in controls (15%). The comparison of
      the combined frequency of CT and TT genotypes with the frequency of the CC
      genotype again showed significant association in AAD (OR 2.63, 95% CI 1.98-5.90,
      p = 0.009) and the irreducible (OR 2.5, 95% CI 1.1-5.74, p = 0.016) subgroup.
      There was, however, no significant association of MTHFR 1298A-->C polymorphism
      with AAD. CONCLUSIONS: Both MTHFR 677C-->T polymorphism and higher T allele
      frequency have significant associations with AAD, especially the irreducible
      variety. Perhaps adequate supplementation of periconceptional folic acid to
      circumvent effects of this missense mutation (as is done for prevention of NTDs)
      would reduce the incidence of AAD.

PMID- 18074688
TI  - The effect of ketoprophen on lumbar spinal fusion healing in a rabbit model.
      Laboratory investigation.
AB  - OBJECT: Several reports have shown that nonsteroidal antiinflammatory drugs
      (NSAIDs) have an inhibitory effect in osteogenesis and reduce heterotopic
      ossification in humans. A deleterious effect of NSAIDs in posterolateral
      intertransverse process fusion has also been suggested. The authors used a
      validated rabbit model to try to determine the influence of the NSAID ketoprophen
      on the fusion rate in lumbar spinal arthrodesis. METHODS: Thirty New Zealand male
      rabbits underwent posterolateral (intertransverse process) bilateral spinal
      fusions at a single level, using autologous bone graft obtained from both iliac
      crests. The animals were randomized after the operation, so that 15 rabbits
      received ketoprophen as a postoperative analgesic and the other 15 received the
      postoperative analgesic tramadol. The animals were killed 8 weeks after surgery,
      and fusion status was determined by inspection, palpation, anteroposterior
      radiographs, and histological analysis. RESULTS: A solid fusion was obtained in
      eight rabbits (53%), and pseudarthrosis in seven rabbits (47%) in each group.
      CONCLUSIONS: These findings suggest that the use of ketoprophen after
      intertransverse spinal fusion at a single level does not decrease the fusion
      rate, compared with tramadol.

PMID- 18074689
TI  - Physical limitations to tissue engineering of intervertebral disc cells: effect
      of extracellular osmotic change on glycosaminoglycan production and cell
      metabolism. Laboratory investigation.
AB  - OBJECT: In this study, the authors examined how physiological levels of
      extracellular osmolality influence proteoglycan accumulation in nucleus pulposus
      cells in a 3D culture system. METHODS: Cells were isolated from the nucleus
      pulposus of caudal discs obtained from 18- to 24-month-old bovines. They were
      cultured for 6 days in alginate beads at 4 million cells/ml in Dulbecco modified
      Eagle medium containing 6% fetal bovine serum under 21% O2. Medium osmolality was
      altered by NaCl addition between 270 and 570 mOsm and monitored using a freezing
      point osmometer. The cell viability profile was determined by manual counting
      after trypan blue staining. Profiles across intact beads were determined by
      manual counting by using fluorescent probes and a transmission electron
      microscope. Lactate production was measured enzymatically, and glycosaminoglycan
      (GAG) accumulation was measured using a dimethylmethylene blue assay. Rate of
      sulfate GAG synthesis was measured using a standard [35S]sulfate radioactive
      method. RESULTS: The cell viability was similar for the high- and low-osmolality
      cultures. However, confocal microscopy showed that the cells were the largest at
      270 mOsm and became smaller with increasing osmotic pressure. The GAG production
      was largest at 370 mOsm, the capacity for GAG production and cell metabolism
      (lactate production) was low under hypoosmolality and hyperosmolality, and cell
      death was observed on electron microscopy. CONCLUSIONS: In the authors' model,
      the prevailing osmolality was a powerful regulator of GAG accumulation by
      cultured nucleus cells. Thus, these results indicate that GAG synthesis rates are
      regulated by GAG concentration, with implications both for the cause of
      degeneration and for tissue engineering.

PMID- 18074690
TI  - Neuroprotective potential of erythropoietin and darbepoetin alfa in an
      experimental model of sciatic nerve injury. Laboratory investigation.
AB  - OBJECT: The objectives of this study were to examine whether the systemic
      administration of recombinant human erythropoietin (rHuEPO) and its long-lasting
      derivative darbepoetin alfa expedited functional recovery in a rat model of
      sciatic nerve injury, and to compare the effects of these agents in the model.
      METHODS: Thirty male Sprague-Dawley rats received a crush injury to the left
      sciatic nerve and subsequently underwent either placebo treatment, daily
      injections of rHuEPO, or weekly injections of darbepoetin alfa. RESULTS: Both
      rHuEPO and darbepoetin alfa were effective in reducing neurological impairment
      and improving compound muscle action potentials following nerve injury.
      Darbepoetin alfa, however, shortened the duration of peripheral nerve
      recovery'and facilitated recovery from the neurological and electrophysiological
      impairment following crush injury significantly better than rHuEPO. Examination
      of the footprint length factor data revealed that darbepoetin alfa-treated
      animals recovered preinjury function by postoperative Day 10, 4 days earlier than
      animals treated with rHuEPO and 11 days earlier than animals treated with
      placebo. CONCLUSIONS: These results suggest that recovery of neurological
      function in a model of peripheral nerve injury is more rapid with weekly
      administration of darbepoetin alfa than with daily rHuEPO treatment. Agents that
      facilitate nerve regeneration have the potential to limit the extent of motor
      endplate loss and muscle atrophy. The administration of EPO in its long-lasting
      recombinant forms affords significant neuroprotection in peripheral nerve injury
      models and may hold promise for future clinical applications.

PMID- 18074691
TI  - Acute paraparesis from hemorrhagic spinal ependymoma: diagnostic dilemma and
      surgical management. Report of two cases and review of the literature.
AB  - Spinal ependymomas are a common type of primary spinal cord neoplasm that
      frequently occurs in the lumbar spine. The authors report on two patients who
      presented with acute neurological decline after hemorrhage into ependymomas of
      the filum terminale. Both were transferred to the authors' institution because of
      diagnostic uncertainty and a concern about possible intradural vascular
      abnormalities. Both patients underwent lumbar laminectomies for tumor resection.
      The pathological finding in each case was myxopapillary ependymoma. Both patients
      made a significant recovery and were ambulatory and continent at follow-up
      review. These cases illustrate the rare but clinically significant incidence of
      acute neurological decline caused by hemorrhagic cauda equina ependymomas,
      including the potential for delayed diagnosis and treatment.

PMID- 18074692
TI  - Long-term survival enhanced by cordectomy in a patient with a spinal glioblastoma
      multiforme and paraplegia. Case report.
AB  - Spinal glioblastomas multiforme (GBMs) are rare lesions of the central nervous
      system with a prognosis as poor as that of their intracranial counterpart. The
      authors present a case of a 50-year-old man with a GBM of the spinal cord treated
      with surgical removal of the mass and cordectomy after the onset of paraplegia.
      Six years later, the patient developed hepatitis C and received interferon
      therapy. Six months after the start of interferon therapy, magnetic resonance
      imaging revealed a right cerebellar mass pathologically consistent with a GBM.
      Despite aggressive treatment, the patient died 1 month later. Although
      intracranial dissemination of spinal GBMs has been reported, this case
      illustrates the longest reported interval between the occurrence of a spinal GBM
      and its intracranial dissemination. Thus, cordectomy should be considered as a
      reasonable alternative in patients with complete loss of neurological function at
      and below the level where they harbor a malignant spinal cord astrocytoma.

PMID- 18074693
TI  - Dissecting aneurysm of the radiculomedullary artery originating from extracranial
      vertebral artery dissection in a patient with rheumatoid cervical spine disease:
      an unusual cause of subarachnoid hemorrhage. Case report.
AB  - The authors report the case of a 65-year-old woman with atlantoaxial subluxation
      caused by rheumatoid arthritis. The patient had been hospitalized because of an
      infection after a total-knee replacement, when she suddenly lost consciousness
      and became apneic after an episode of intractable neck pain. Cranial computed
      tomography scanning demonstrated subarachnoid hemorrhage (SAH), and angiography
      revealed a dissecting aneurysm of the radiculomedullary artery that had
      originated from an extracranial vertebral artery dissection at the level of the
      atlantoaxial joint. Although coil embolization for the parent artery, including
      the dissecting aneurysm, was performed successfully, the patient died of
      worsening infection. The authors believe that the SAH occurred because of a
      ruptured dissecting aneurysm in the intradural portion of the radiculomedullary
      artery.

PMID- 18074694
TI  - Iatrogenic pyogenic osteomyelitis of C-1 and C-2 treated with transoral
      decompression and delayed posterior occipitocervical arthrodesis. Case report.
AB  - The authors describe a case of osteomyelitis of the craniocervical junction
      caused by iatrogenic infection of the spine during corticosteroid injection
      therapy. This 58-year-old diabetic man presented with acute exacerbation of neck
      pain that had began 4 months prior to admission. He did not experience the
      associated fever, chills, or sweats, but he did notice transient weakness in the
      right upper extremity. A computed tomography (CT) scan of the cervical spine
      demonstrated a destructive process involving the odontoid and the left
      occipitocervical and atlantoaxial joints that was not present on a CT obtained 2
      months earlier, just before trigger-point and left-sided C1-2 facet joint
      corticosteroid injections. A diagnosis of staphylococcal osteomyelitis was made,
      and initial treatment with external immobilization and appropriate antibiotic
      therapy failed to control radiographically demonstrated and clinical progression.
      The patient was successfully treated using staged anterior decompression and
      posterior instrumented fusion with prolonged antibiotic therapy. To the authors'
      knowledge this case is the first reported instance of iatrogenic pyogenic
      osteomyelitis of the craniocervical junction successfully treated with anterior
      decompression and delayed posterior arthrodesis.

PMID- 18074695
TI  - Anterolateral approach to the cervical spine: major anatomical structures and
      landmarks. Technical note.
AB  - OBJECT: The authors undertook a study to explore the topographic anatomical
      features seen during the anterolateral approach to cervical spine, anatomical
      variations, and certain landmarks related to the surgical procedure. METHODS: The
      study was conducted in 30 fresh cadavers. RESULTS: The common carotid artery
      bifurcation was mostly found at the level of C-4 (78%). The inferior belly of the
      omohyoid muscle was seen to cross the sternocleidomastoid muscle at the C5-6 disc
      level along the entire C-6 vertebral body. To reach the lower cervical region,
      the sacrifice of this muscle makes the procedure easier. The facial vein drained
      into the internal jugular vein mostly at the level of C3-4 (54%). The superior
      ganglion of the cervical sympathetic chain was located at the C-4 vertebra, but
      the location of the intermediate ganglion exhibited some variation. The vertebral
      artery entered the transverse foramen of C-6 in 27 cadavers (90%), the transverse
      foramen of C-7 in two cadavers (7%), and the transverse foramen of C-4 in one
      cadaver (3%). Because the inferior thyroid artery crossed the C6-7 interspace
      obliquely, the course of the inferior thyroid artery may complicate the
      procedure. The C-5 uncinate process was shortest and narrowest and had the
      greatest distance from the medial edge of the process to the anterior tubercle (p
      < 0.001). CONCLUSIONS: Understanding the qualitative anatomy of this region not
      only improves the safety of anterior and anterolateral cervical spine surgery but
      also allows adequate decompression of neural elements and resolution of the other
      pathological processes of this region. In this fresh cadaveric study, our goal
      was to improve the approach and decrease the incidence of complications.

PMID- 18074696
TI  - Anterior lumbar surgery.

PMID- 18074697
TI  - Spatial awareness in synthetic vision systems: using spatial and temporal
      judgments to evaluate texture and field of view.
AB  - OBJECTIVE: This work introduced judgment-based measures of spatial awareness and
      used them to evaluate terrain textures and fields of view (FOVs) in synthetic
      vision system (SVS) displays. BACKGROUND: SVSs are cockpit technologies that
      depict computer-generated views of terrain surrounding an aircraft. In the
      assessment of textures and FOVs for SVSs, no studies have directly measured the
      three levels of spatial awareness with respect to terrain: identification of
      terrain, its relative spatial location, and its relative temporal location.
      METHODS: Eighteen pilots made four judgments (relative azimuth angle, distance,
      height, and abeam time) regarding the location of terrain points displayed in 112
      noninteractive 5-s simulations of an SVS head-down display. There were two
      between-subject variables (texture order and FOV order) and five within-subject
      variables (texture, FOV, and the terrain point's relative azimuth angle,
      distance, and height). RESULTS: Texture produced significant main and interaction
      effects for the magnitude of error in the relative angle, distance, height, and
      abeam time judgments. FOV interaction effects were significant for the
      directional magnitude of error in the relative distance, height, and abeam time
      judgments. CONCLUSION: Spatial awareness was best facilitated by the elevation
      fishnet (EF), photo fishnet (PF), and photo elevation fishnet (PEF) textures.
      APPLICATION: This study supports the recommendation that the EF, PF, and PEF
      textures be further evaluated in future SVS experiments. Additionally, the
      judgment-based spatial awareness measures used in this experiment could be used
      to evaluate other display parameters and depth cues in SVSs.

PMID- 18074698
TI  - Identifying problems and generating recommendations for enhancing complex
      systems: applying the abstraction hierarchy framework as an analytical tool.
AB  - OBJECTIVE: This study adopts J. Rasmussen's (1985) abstraction hierarchy (AH)
      framework as an analytical tool to identify problems and pinpoint opportunities
      to enhance complex systems. BACKGROUND: The process of identifying problems and
      generating recommendations for complex systems using conventional methods is
      usually conducted based on incompletely defined work requirements. As the
      complexity of systems rises, the sheer mass of data generated from these methods
      becomes unwieldy to manage in a coherent, systematic form for analysis. There is
      little known work on adopting a broader perspective to fill these gaps. METHOD:
      AH was used to analyze an aircraft-automation system in order to further identify
      breakdowns in pilot-automation interactions. Four steps follow: developing an AH
      model for the system, mapping the data generated by various methods onto the AH,
      identifying problems based on the mapped data, and presenting recommendations.
      RESULTS: The breakdowns lay primarily with automation operations that were more
      goal directed. Identified root causes include incomplete knowledge content and
      ineffective knowledge structure in pilots' mental models, lack of effective
      higher-order functional domain information displayed in the interface, and lack
      of sufficient automation procedures for pilots to effectively cope with
      unfamiliar situations. CONCLUSION: The AH is a valuable analytical tool to
      systematically identify problems and suggest opportunities for enhancing complex
      systems. It helps further examine the automation awareness problems and identify
      improvement areas from a work domain perspective. APPLICATION: Applications
      include the identification of problems and generation of recommendations for
      complex systems as well as specific recommendations regarding pilot training,
      flight deck interfaces, and automation procedures.

PMID- 18074699
TI  - Acquisition and transfer of attention allocation strategies in a multiple-task
      work environment.
AB  - OBJECTIVE: Payoff effects on strategy development and change were assessed in a
      synthetic work environment, SYNWORK1. BACKGROUND: Many work settings require
      several tasks to be performed concurrently. It is important to know how the
      strategies used in performing the respective tasks vary with payoffs. METHOD:
      Sixty students performed four tasks in SYNWORK1, for which points are received
      for correct responses and lost for incorrect responses. Individual-task payoffs
      were varied between participants and were changed after 8 and 12 sessions to
      examine the effects of a previous strategy on development of a new strategy.
      RESULTS: Participants were sensitive to initial payoffs and modified their
      strategies when payoffs changed. However, residual effects of prior payoffs were
      evident. CONCLUSION: Payoffs for multiple-task environments need to be explicit,
      and practice should be provided for strategy development. When payoffs change,
      strategies adopted reflect current and previous payoffs. APPLICATION: The
      findings can be applied to the design of payoff schedules for multiple-task
      environments.

PMID- 18074700
TI  - Performance enhancement in an uninhabited air vehicle task using
      psychophysiologically determined adaptive aiding.
AB  - OBJECTIVE: We show that psychophysiologically driven real-time adaptive aiding
      significantly enhances performance in a complex aviation task. A further goal was
      to assess the importance of individual operator capabilities when providing
      adaptive aiding. BACKGROUND: Psychophysiological measures are useful for
      monitoring cognitive workload in laboratory and real-world settings. They can be
      recorded without intruding into task performance and can be analyzed in real
      time, making them candidates for providing operator functional state estimates.
      These estimates could be used to determine if and when system intervention should
      be provided to assist the operator to improve system performance. METHODS:
      Adaptive automation was implemented while operators performed an uninhabited
      aerial vehicle task. Psychophysiological data were collected and an artificial
      neural network was used to detect periods of high and low mental workload in real
      time. The high-difficulty task levels used to initiate the adaptive automation
      were determined separately for each operator, and a group-derived mean difficulty
      level was also used. RESULTS: Psychophysiologically determined aiding
      significantly improved performance when compared with the no-aiding conditions.
      Improvement was greater when adaptive aiding was provided based on individualized
      criteria rather than on group-derived criteria. The improvements were
      significantly greater than when the aiding was randomly provided. CONCLUSION:
      These results show that psychophysiologically determined operator functional
      state assessment in real time led to performance improvement when included in
      closed loop adaptive automation with a complex task. APPLICATION: Potential
      future applications of this research include enhanced workstations using adaptive
      aiding that would be driven by operator functional state.

PMID- 18074701
TI  - Ergonomic evaluation of the ambulance interior to reduce paramedic discomfort and
      posture stress.
AB  - OBJECTIVE: This study aims to evaluate safety and accessibility of an advanced
      life support (ALS) ambulance interior. BACKGROUND: The standard ambulance's
      interior design is unsatisfactory based on perceived discomfort and postures that
      constrain paramedics and medical staff, resulting in unsafe treatment of
      patients, mainly when being transported. METHODS: Two procedures were used to
      evaluate performance during a wide range of rescue tasks: a survey, based on
      questionnaires, interviews, and observation of paramedics performing routine
      tasks; and upper body and back posture analysis, based on postural
      considerations. RESULTS: Findings revealed that 74% of the paramedics stated that
      the location of the paramedic's seat is inefficient while they perform clinical
      procedures; 94% found the bench uncomfortable; 77% felt that the vertical
      distance between the bench and the stretcher is too far; and 86% needed to steady
      themselves when the vehicle was moving. Posture analysis showed that paramedics
      undergo several nonneutral back postures, including twisted back (>20 degrees)
      and sitting with back flexion between 20 degrees and 45 degrees. CONCLUSION:
      Because the interior of the ALS ambulance was found to be unsatisfactory both to
      paramedics and patients, alternative design issues are proposed. APPLICATION: The
      suggested practical layout contains four main modifications: (a) replacing the
      bench with two adjustable paramedic seats, (b) redesigning the medical cabinet
      for easy access, (c) adding an adjustable folding seat opposite the two new
      seats, and (d) adding a swiveling base and lifting apparatus that will
      accommodate the stretcher and enable better accessibility to patients by the
      paramedic personnel.

PMID- 18074702
TI  - Thermal comfort and sensation in men wearing a cooling system controlled by skin
      temperature.
AB  - OBJECTIVE: The study was done to determine whether thermal comfort (TC), thermal
      sensation (TS), and subjective factors gauging environmental stress were
      negatively affected with different cooling methods in men exercising in chemical
      protective clothing. BACKGROUND: Previous studies have reported that intermittent
      regional cooling improved the efficacy of cooling as compared with constant
      cooling (CC), but no studies have addressed whether there is any improvement in
      thermal comfort. METHODS: Eight male volunteers exercised at moderate work
      intensity (425 W) in three microclimate cooling tests. The circulating fluid in
      the cooling garment was provided during exercise to the head (6% body surface
      area [BSA]), torso (22% BSA), and thighs (44% BSA) and manipulated under three
      methods: (a) CC, (b) pulsed cooling (PC), and (c) PC activated by mean skin
      temperature (T(sk)) control (PC(skin)). TC and TS ratings were recorded every 20
      min during the 80-min test. RESULTS: TC and TS ratings were not different for
      PC(skin) and CC; thus the participants perceived PC(skin) as being similar to CC.
      TS was significantly warmer with PC than with PC(skin) and CC (p < .001). In
      PC(skin), T(sk) was significantly higher than in PC and CC (p < .001), and
      PC(skin) was rated as being not as warm as PC according to TS. CONCLUSION: This
      indicates that the PC(skin) method was perceived as being as cool as CC and
      cooler than PC. APPLICATION: These findings indicate that the PC(skin) cooling
      method is an acceptable alternative to CC and PC based on human perceptions.

PMID- 18074703
TI  - Effects of speech- and text-based interaction modes in natural language human
      computer dialogue.
AB  - OBJECTIVE: This study examined the effects of user production (speaking and
      typing) and user reception (listening and reading) modes on natural language
      human-computer dialogue. BACKGROUND: Text-based dialogue is often more efficient
      than speech-based dialogue, but the latter is more dynamic and more suitable for
      mobile environments and hands-busy situations. The respective contributions of
      user production and reception modes have not previously been assessed. METHOD:
      Eighteen participants performed several information search tasks using a natural
      language information system in four experimental conditions: phone (speaking and
      listening), Web (typing and reading), and mixed (speaking and reading or typing
      and listening). RESULTS: Mental workload was greater and participants'
      repetitions of commands were more frequent when speech (speaking or listening)
      was used for both the user production and reception modes rather than text
      (typing or reading). Completion times were longer for listening than for reading.
      Satisfaction was lower, utterances were longer, and the interaction error rate
      was higher for speaking than typing. CONCLUSION: The production and reception
      modes both contribute to dialogue and mental workload. They have distinct
      contributions to performance, satisfaction, and the form of the discourse.
      APPLICATION: The most efficient configuration for interacting in natural language
      would appear to be speech for production and system prompts in text, as this
      combination decreases the time on task while improving dialogue involvement.

PMID- 18074704
TI  - Social facilitation effects of virtual humans.
AB  - OBJECTIVE: To investigate whether virtual humans produce social facilitation
      effects. BACKGROUND: When people do an easy task and another person is nearby,
      they tend to do that task better than when they are alone. Conversely, when
      people do a hard task and another person is nearby, they tend to do that task
      less well than when they are alone. This phenomenon is referred to in the social
      psychology literature as social facilitation. The present study investigated
      whether virtual humans can evoke a social facilitation response. METHOD:
      Participants were given different tasks to do that varied in difficulty. The
      tasks involved anagrams, mazes, and modular arithmetic. They did the tasks alone,
      in the company of another person, or in the company of a virtual human on a
      computer screen. RESULTS: For easy tasks, performance in the virtual human
      condition was better than in the alone condition, and for difficult tasks,
      performance in the virtual human condition was worse than in the alone condition.
      CONCLUSION: As with a human, virtual humans can produce social facilitation.
      APPLICATION: The results suggest that designers of virtual humans should be
      mindful about the social nature of virtual humans; a design decision as to when
      and how to present a virtual human should be a deliberate and informed decision.
      An ever-present virtual human might make learning and performance difficult for
      challenging tasks.

PMID- 18074705
TI  - Cough once for danger: icons versus abstract warnings as informative alerts in
      civil aviation.
AB  - OBJECTIVE: An experiment investigated the efficacy of auditory icons as warning
      signals in an aviation context. BACKGROUND: Iconic signals, such as a cough to
      signal dangerous levels of carbon monoxide, convey information about the nature
      of an incident and alert the operator that there is a problem, whereas signals
      that are arbitrarily associated with a critical incident provide relatively less
      information. Warning recognition speed and accuracy are likely to be influenced
      by modality of presentation (visual, auditory, auditory + visual) and task demand
      (low, high). METHODS: The 172 participants completed a computer-based training
      session and test task that involved responding to abstract or iconic auditory (1
      s), visual, or auditory + visual warnings associated with seven critical
      incidents while performing low- and high-demand concurrent tasks. RESULTS:
      Significantly fewer training trials were required to learn iconic warnings than
      abstract warnings. An advantage for iconic warnings persisted into the test
      phase, evident most consistently as greater warning recognition accuracy. The
      effect was observed in both high- and low-demand conditions. Auditory abstract
      warnings, in particular, elicited slow reaction times and poor accuracy.
      CONCLUSION: Associations between a small number of meaningful environmental
      sounds and critical incidents can be learned with ease relative to more abstract
      associations, although training is required and response times are relatively
      slow. APPLICATION: Sets of distinctive auditory iconic warnings can be designed
      to alert and inform pilots about non-time-pressured events. Potential
      applications of language-neutral icons as informative warnings include civil,
      commercial, and defense aircraft.

PMID- 18074706
TI  - The search for complex problem-solving strategies in the presence of stressors.
AB  - OBJECTIVE: The present research tests the effects of time pressure and noise on
      open-mindedness to discover new problem-solving strategies. BACKGROUND: We are
      primarily interested in transfer of skill from one phase to the next. More
      specifically, this study investigates whether the presence of stressors makes
      participants adhere to the sustained use of complex rules. METHOD: Participants
      learned to apply a complex rule in the first phase of a category learning task.
      In the second phase, this rule became dysfunctional and participants had to
      search for a new categorization rule in order to assign the stimuli to the
      correct classes. Two experiments were set up to investigate this issue. RESULTS:
      Participants were found to have difficulty discovering a complex Phase 2 rule in
      the presence of stressors, whereas the discovery of a simple rule was not
      hindered by the presence of stressors. CONCLUSION: In the discussion, it is
      argued that the present results are compatible with previous research on
      stressors showing that time pressure and noise induce the application of simple
      strategies. The innovative finding here is that this simplification also occurs
      in individuals who are accustomed to using complex solutions. APPLICATION: The
      implications of the present results for emergency response training are
      elaborated upon.

PMID- 18074707
TI  - Binocular rivalry and head-worn displays.
AB  - OBJECTIVE: We provide a review and analysis of much of the published literature
      on binocular rivalry that is relevant to the design and use of head-worn displays
      (HWDs). BACKGROUND: This review draws heavily from both the basic vision
      literature and applied HWD literature in order to help provide insight for
      minimizing the effects of binocular rivalry when HWDs are worn. METHOD: Included
      in this review are articles and books found cited in other works as well as
      articles and books obtained from an Internet search. RESULTS: Issues discussed
      and summarized are (a) characteristics of binocular rivalry, (b) stimulus factors
      affecting rivalry, (c) cognitive variables affecting rivalry, and (d) tasks
      affected by rivalry. CONCLUSION: This paper offers a set of recommendations for
      minimizing the effects of binocular rivalry when HWDs are used as well as
      recommendations for future research. APPLICATION: Considerations of the basic
      vision literature on binocular rivalry will provide insight for future design
      solutions for HWDs.

PMID- 18074708
TI  - Effects of single versus multiple warnings on driver performance.
AB  - OBJECTIVE: To explore how a single master alarm system affects drivers' responses
      when compared with multiple, distinct warnings. BACKGROUND: Advanced driver
      warning systems are intended to improve safety, yet inappropriate integration may
      increase the complexity of driving, especially in high workload situations. This
      study investigated the effects of auditory alarm scheme, reliability, and
      collision event type on driver performance. METHOD: Using a 2 x 2 x 4 mixed
      factorial design, we investigated the impact of two alarm schemes (master vs.
      individual) and two levels of alarm reliability (high and low) on distracted
      drivers' performance across four collision event types (frontal collision
      warnings, left and right lane departure warnings, and warnings for a fast
      approaching following vehicle). RESULTS: Participants' reaction times and
      accuracy rates were significantly affected by the type of collision event and
      alarm reliability. The use of individual alarms, rather than a single master
      alarm, did not significantly affect driving performance in terms of reaction time
      or response accuracy. CONCLUSION: Even though a master alarm is a relatively
      uninformative warning, it produced statistically no different reaction times or
      accuracy results when compared with information-rich auditory icons, some of
      which were spatially located. In addition, unreliable alarms negatively impacted
      driver performance, regardless of event type or alarm scheme. APPLICATION: These
      results have important implications for the development and implementation of
      multiple driver warning systems.

PMID- 18074709
TI  - Multisensory in-car warning signals for collision avoidance.
AB  - OBJECTIVE: A driving simulator study was conducted in order to assess the
      relative utility of unimodal auditory, unimodal vibrotactile, and combined
      audiotactile (i.e., multisensory) in-car warning signals to alert and inform
      drivers of likely front-to-rear-end collision events in a situation modeled on
      real-world driving. BACKGROUND: The implementation of nonvisual in-car warning
      signals may have important safety implications in lessening any visual overload
      during driving. Multisensory integration can provide synergistic facilitation
      effects. METHOD: The participants drove along a rural road in a car-following
      scenario in either the presence or absence of a radio program in the background.
      The brake light signals of the lead vehicle were also unpredictably either
      enabled or disabled on a trial-by-trial basis. RESULTS: The results showed that
      the participants initiated their braking responses significantly more rapidly
      following the presentation of audiotactile warning signals than following the
      presentation of either unimodal auditory or unimodal vibrotactile warning
      signals. CONCLUSION: Multisensory warning signals offer a particularly effective
      means of capturing driver attention in demanding situations such as driving.
      APPLICATION: The potential value of such multisensory in-car warning signals is
      explained with reference to recent cognitive neuroscience research.

PMID- 18074710
TI  - Effects of age and illumination on night driving: a road test.
AB  - OBJECTIVE: This study investigated the effects of drivers' age and low light on
      speed, lane keeping, and visual recognition of typical roadway stimuli.
      BACKGROUND: Poor visibility, which is exacerbated by age-related changes in
      vision, is a leading contributor to fatal nighttime crashes. There is little
      evidence, however, concerning the extent to which drivers recognize and
      compensate for their visual limitations at night. METHOD: Young, middle-aged, and
      elder participants drove on a closed road course in day and night conditions at a
      "comfortable" speed without speedometer information. During night tests,
      headlight intensity was varied over a range of 1.5 log units using neutral
      density filters. RESULTS: Average speed and recognition of road signs decreased
      significantly as functions of increased age and reduced illumination. Recognition
      of pedestrians at night was significantly enhanced by retroreflective markings of
      limb joints as compared with markings of the torso, and this benefit was greater
      for middle-aged and elder drivers. Lane keeping showed nonlinear effects of
      lighting, which interacted with task conditions and drivers' lateral bias,
      indicating that older drivers drove more cautiously in low light. CONCLUSION:
      Consistent with the hypothesis that drivers misjudge their visual abilities at
      night, participants of all age groups failed to compensate fully for diminished
      visual recognition abilities in low light, although older drivers behaved more
      cautiously than the younger groups. APPLICATION: These findings highlight the
      importance of educating all road users about the limitations of night vision and
      provide new evidence that retroreflective markings of the limbs can be of great
      benefit to pedestrians' safety at night.

PMID- 18074711
TI  - Collaborative training with a more experienced partner: remediating low
      pretraining self-efficacy in complex skill acquisition.
AB  - OBJECTIVE: This study examined the effectiveness of collaborative training for
      individuals with low pretraining self-efficacy versus individuals with high
      pretraining self-efficacy regarding the acquisition of a complex skill that
      involved strong cognitive and psychomotor demands. BACKGROUND: Despite support
      for collaborative learning from the educational literature and the similarities
      between collaborative learning and interventions designed to remediate low self
      efficacy, no research has addressed how self-efficacy and collaborative learning
      interact in contexts concerning complex skills and human-machine interactions.
      METHOD: One hundred fifty-five young male adults trained either individually or
      collaboratively with a more experienced partner on a complex computer task that
      simulated the demands of a dynamic aviation environment. Participants also
      completed a task-specific measure of self-efficacy before, during, and after
      training. RESULTS: Collaborative training enhanced skill acquisition
      significantly more for individuals with low pretraining self-efficacy than for
      individuals with high pretraining self-efficacy. However, collaborative training
      did not bring the skill acquisition levels of those persons with low pretraining
      self-efficacy to the levels found for persons with high pretraining self
      efficacy. Moreover, tests of mediation suggested that collaborative training may
      have enhanced appropriate skill development strategies without actually raising
      self-efficacy. CONCLUSION: Although collaborative training can facilitate the
      skill acquisition process for trainees with low self-efficacy, future research is
      needed that examines how the negative effects of low pretraining self-efficacy on
      complex skill acquisition can be more fully remediated. APPLICATION: The
      differential effects of collaborative training as a function of self-efficacy
      highlight the importance of person analysis and tailoring training to meet
      differing trainee needs.

PMID- 18074712
TI  - Cardiovascular centers of excellence program: a system approach for improving the
      care and outcomes of cardiovascular patients at HCA hospitals.
AB  - BACKGROUND: A voluntary continuous quality improvement (CQI) effort, the
      cardiovascular Centers of Excellence (COE) program was implemented by HCA, Inc.,
      to improve cardiovascular care in its hospital system. METHODS: The
      cardiovascular COE program targeted 165 hospitals that provide cardiovascular
      services in at least one major service area. Awards (unrestricted grants)
      provided hospitals with an incentive to participate. RESULTS: One hundred fifty
      eight hospitals (95.8%) completed the entire 2005 cardiovascular COE program;
      five were identified as cardiovascular COE. The program developed three key CQI
      activities: (1) an ongoing Web-based survey to inventory, track, and verify
      evidence-based practices across all aspects of patient care, including clinical
      practices, leadership, communications, patient safety, and patient education; (2)
      quarterly benchmark reports tracking risk-adjusted outcomes and evidence-based
      practices; and (3) regularly scheduled educational programs presented by an
      interdisciplinary team in which lessons learned from an institution's successful,
      evidence-based, best-practice implementation were discussed. DISCUSSION: The COE
      program successfully encouraged facilities to proacrively investigate their
      evidence-based clinical standards and outcomes.

PMID- 18074713
TI  - Reducing surgical complications.
AB  - BACKGROUND: One of the 12 interventions that the Institute for Healthcare
      Improvement (IHI) recommends for its 5 Million Lives Campaign is "Reduce Surgical
      Complications...by reliably implementing all the changes in care recommended by
      the Surgical Care Improvement Project (SCIP)." Many surgical patients experience
      complications from surgery, some of which are preventable with the reliable
      application of evidence-based medicine. Despite promotion and dissemination of
      recommendations and practices, overall national compliance remains less than
      optimal. METHODS: IHI's 5 Million Lives Campaign is supporting the recommended
      practices in the SCIP to accelerate adoption for reduction in surgical
      complications by 25% by December 2008. Practices relate to surgical site
      infection prevention, prophylaxis for venousthromboembolism, continuation of beta
      blockers, and prevention of postoperative pneumonia. Strategies used in hospitals
      that have achieved improvement in the recommended SCIP measures include practices
      that increase reliability and minimize practice variation. These changes, along
      with efforts to improve teamwork and communication, are essential to reduce
      surgical complications. CONCLUSION: Organizations that strive for high
      reliability in their processes should see improvement in the associated outcomes
      and a reduction in harm to patients.

PMID- 18074714
TI  - Case study: preventing surgical complications at Baystate Medical Center.
AB  - An academic medical center's experience in a collaborative surgical infection
      prevention project may be instructive for other organizations.

PMID- 18074715
TI  - The influence of care management tools on physician practice change across
      organizational settings.
AB  - BACKGROUND: A study was conducted to assess whether physician reports of practice
      change were associated with the type of health care organization delivering the
      tools and the type or number of tools received. METHODS: A mail survey was sent
      in 2001 to primary care physicians practicing in the 13 largest urban counties in
      California. RESULTS: Physicians were more likely to report a practice change if
      they received care management tools from a medical group (28%) or a group/staff
      model health maintenance organization (HMO; 24%) than if they received tools from
      a health plan (9%; p = .01 and p =.005, respectively). HMO physicians were
      significantly more likely to receive each type of tool than other physicians.
      After adjusting for the type or number of tools, the receipt of care management
      tools from medical groups, but not HMOs, remained a significant predictor of
      practice change. Physicians reported practice change in association with the
      number of tools received from a medical group (adjusted odds ratio [AOR] 1.49;
      95% confidence interval [CI] 1.08-2.06) and the tools received from an
      independent practice association, health plan, or hospital outside a medical
      group (AOR 1.21; 95% CI 1.03-1.42). DISCUSSION: Medical groups have the strongest
      influence on practice change, whereas group/staff model HMOs have the highest
      level of implementation.

PMID- 18074716
TI  - Developing a Spanish-language consumer report for CAHPS health plan surveys.
AB  - BACKGROUND: A Spanish-language consumer report on health plan quality was
      developed for the Consumer Assessments of Healthcare Providers and Systems
      (CAHPS) project. METHODS: Multiple translations, a committee review, and a
      readability assessment were performed to produce a draft Spanish report. The
      report was revised on the basis of a series of cognitive interviews with 24
      Latinos. RESULTS: The median age of participants was 41 years, and the median
      number of years in the United States was 9; 67% were female, and 63% had less
      than a high school education. In general, participants understood the report and
      said they would use it to choose a health plan. Less-educated respondents had
      difficulty understanding the segmented bar graphs that showed the proportion of
      health plan members' responses. A summary chart comparing all health plans on all
      dimensions was easier to comprehend when differences were represented by word
      icons rather than by stars. DISCUSSION: Concepts and terms about health care
      quality translated well from English to Spanish. Simplifying graphical
      information involves losing some detail but makes information more usable.
      Summary charts facilitate comparisons across plans, but differences relative to a
      mean are difficult for both Spanish- and English-speaking consumers to
      understand.

PMID- 18074717
TI  - Attitudes toward medical device use errors and the prevention of adverse events.
AB  - BACKGROUND: The design of a device's user interface often contributes to the
      chance of a user making an error in using the device. However, there is evidence
      that most such errors that occur in practice are attributed solely to the user
      and that the primary method of error prevention is to retrain the user. Yet this
      attitude may decrease the quality of error reports and the use of more effective
      error prevention strategies. A qualitative study was conducted to assess health
      care employees' attitudes toward device use errors and the prevention of adverse
      events. METHODS: Twenty-six health care employees from three hospital systems,
      including 11 device users and 15 nonusers who had participated in infusion pump
      purchasing decisions were given a scenario describing a device use error
      involving an infusion pump. Several open-ended questions assessed what they felt
      led to the event and how they would prevent the event from reccurring. RESULTS:
      The top three reported types of factors leading to the adverse event, in
      decreasing order of frequency, were the user, pump design problems, and lack of
      training. The top three prevention strategies reported by the participants were
      retraining the user, redesigning the device, and telling the user to be careful.
      DISCUSSION: These results suggest that health care employees still put too much
      emphasis on the traditional view of blaming and retraining the user.

PMID- 18074718
TI  - Using the rapid response system to provide better oversight of patient care
      processes.
AB  - The cross-disciplinary nature of patient care and medical emergency teams allows
      for identification of systemwide problems that might otherwise be perceived as
      isolated events.

PMID- 18074719
TI  - A check-up for safety culture in "my patient care area".
AB  - The two-page Culture Check-Up Tool, which takes 30 to 60 minutes to complete as a
      group exercise, can help clinicians recognize and fix culture problems.

PMID- 18074720
TI  - [Granulomatous mastitis: a rare cause of breast swelling].
AB  - Three women, aged 37, 39 and 29 years, presented with unilateral painful swelling
      of the breast. Ultrasound revealed inflammation with abscess formation.
      Histological biopsies contained granulomatous tissue without necrosis.
      Corynebacterium species were cultured in the first two patients. All 3 patients
      were diagnosed with granulomatous mastitis and were successfully treated with
      doxycycline. Granulomatous mastitis is a rare disorder that may mimic breast
      carcinoma. It occurs most frequently in fertile women. Diagnosis is based on
      histological biopsy which shows granulomas without necrosis, while other causes
      of granulomatous inflammation, especially tuberculosis, have been excluded. The
      aetiology is not fully understood. It is hypothesised that the granulomatous
      mastitis is caused by a type IV allergic reaction. Recently an association with
      Corynebacterium species was suggested. Best practice treatment methods are
      unclear. Most patients are treated with surgical intervention and steroids, but
      the rate of recurrence is high (50%). Treatment with doxycycline must be
      considered in patients with cultured Corynebacterium species.

PMID- 18074721
TI  - [Adjusted tobacco legislation and accompanying actions for the benefit of future
      children of women smokers].
AB  - Pregnant women are a population group of special interest as far as smoking is
      concerned. It is not only their own health but also that of their unborn children
      that is implicated. Consequently, achieving short-term abstention is relevant as
      well as long-term cessation. A paper published elsewhere in this issue provides
      empirical evidence on the smoking status of pregnant women and illustrates that
      currently one quarter of them smoke. For approximately 25% of pregnant women,
      their pregnancy is reason to stop smoking and for the majority this then results
      in lasting abstention. However, 11% of pregnant smokers keep on smoking
      throughout their pregnancy. These figures compare favourably with the 28% of
      pregnant women smokers in the Dutch population, but should nevertheless be reason
      for concern for the health of mother and child. One of the reasons for the high
      levels of smokers amongst pregnant women in the Dutch population could well be
      the waning political support for public health actions following tobacco
      legislation that came into effect in 2004. The effectiveness of smoking cessation
      can be enhanced by a combination of individual and public actions. For example,
      partners of smoking pregnant women should also be involved in quitting
      interventions. Moreover, the current and anxiously awaited proposal by the
      Minister of Health to impose a ban on smoking in the public domain of bars and
      restaurants will offer an ideal opportunity for promoting non-smoking on the part
      ofindividuals. Such a development will result in considerable health benefits for
      the unborn children of smoking, pregnant women.

PMID- 18074722
TI  - [Diagnostic and prognostic value of B-type natriuretic peptides in heart failure
      or signs of heart failure].
AB  - Biologically active B-type natriuretic peptide or brain natriuretic peptide (BNP)
      and biologically inactive N-terminal proBNP (NT-proBNP) are secreted into the
      bloodstream by the heart and provide primarily information regarding the filling
      pressures in the heart. The accuracy of plasma BNP levels in the diagnosis of
      heart failure is comparable to that of plasma NT-proBNP levels. Reliable assays
      have been developed for both peptides, some of which can be used for rapid
      diagnosis in the emergency clinic. In both groups of patients with heart failure
      and the general population, there is a relationship between the plasma BNP and NT
      proBNP levels and the risk of cardiovascular death, after correction for the
      traditional risk factors. Screening studies using the determination of BNP or NT
      proBNP levels in order to detect patients with heart failure at an early stage
      cannot be recommended because their specificity is too low: in addition to heart
      failure, the plasma BNP or NT-proBNP level is affected by age, gender, body mass
      index, renal function, and pulmonary capacity. There are indications that the
      introduction ofa rapid BNP determination for patients that present to the
      emergency clinic with acute dyspnoea will lead to more effective diagnosis and
      treatment. Sequential determinations ofthe plasma BNP or NT-proBNP levels in
      inpatients and outpatients with heart failure can help to optimise the treatment,
      thus decreasing the morbidity and mortality that are associated with heart
      failure.

PMID- 18074723
TI  - [Hormonal contraception in men].
AB  - Over the past few decades, female hormonal contraception has been seen to be very
      successful. However, this has still not resulted in a hormonal contraceptive for
      men. Certain injectable combinations ofandrogens and progestagens have been found
      to suppress spermatogenesis. All combinations that have been tested so far suffer
      from a relative lack of efficacy, a long lag time to achieve azoospermia,
      requiring the user to undergo one or more semen analyses, a moderate user
      friendliness, and concerns about the long-term safety and reversibility. It is
      not to be expected that male hormonal contraception will become a serious
      alternative to the already existing female equivalent during the coming 5 years.

PMID- 18074724
TI  - [In favour of performing coronary balloon dilatation in 'smaller' hospitals].
AB  - Until now, the permission to set up a centre for percutaneous coronary
      intervention (PCI) has been governed by Dutch law to ensure the availability and
      quality of PCI procedures. Recently, the Minister of Health proposed abolishing
      this law for PCI procedures. The Dutch Society of Cardiology has issued stringent
      guidelines for PCI centres. Even small hospitals should be able to start a PCI
      programme by following these stringent guidelines.

PMID- 18074725
TI  - [Against coronary balloon dilatation in small hospitals].
AB  - The Dutch Health Council report on 'Invasive cardiac procedures' [Bijzondere
      interventies aan her hart] recommends, for reasons of quality, efficiency and
      patient safety, that cardiac surgery, percutaneous coronary interventions, and
      the invasive treatment of cardiac rhythm disorders be concentrated in a limited
      number of fully equipped cardiac centres. Small hospitals should therefore not
      carry out invasive cardiac procedures.

PMID- 18074726
TI  - [Diagnostic image (350). A woman with a swollen knee. Clear cell sarcoma].
AB  - A 31-year-old woman presented with a slowly growing mass anterior from the right
      patella, due to a clear cell sarcoma.

PMID- 18074727
TI  - [Slight decrease in the prevalence of smoking around pregnancy].
AB  - OBJECTIVE: To establish smoking prevalence of fertile-aged women; before and
      during pregnancy, and 6 months after delivery. DESIGN: Cross-sectional. METHOD:
      Yearly surveys by questionnaires handed out during 2001-2003 to mothers visiting
      a Well Baby Clinic with infants aged 0-6 months. RESULTS: Out ofa total of 14,540
      questionnaires, 9133 (63%) were completed and returned. Before pregnancy 25% of
      all the women concerned smoked, 6% stopped 6 months before getting pregnant; this
      percentage rose between 2001 (5%) and 2003 (7%). During pregnancy, 14% of the
      women smoked. This percentage was significantly lower in 2002 and 2003 (13%)
      compared to 16% in 2001. 11% smoked while pregnant (average 5 cigarettes daily),
      and 3% stopped some time during pregnancy. Of the mothers who quitted smoking
      before or during pregnancy, two thirds did so permanently. Nevertheless 15% of
      all women smoked during the first half year after delivery. This percentage was
      lowest in 2003 (14%) and highest in 2001 (17%). 28% of all mothers with infants
      aged 0-6 months had partners who smoked (daily 10 cigarettes average), these
      women were more likely to start smoking again (RR: 2). CONCLUSION: Minor positive
      changes were observed within the study period. A smoking partner contributed to
      smoking relapse after delivery.

PMID- 18074728
TI  - [Widespread preoperative hair removal in the southwest of The Netherlands despite
      an evidence-based guideline discouraging this practice].
AB  - OBJECTIVE: To determine whether the 1993 guideline from the Dutch Institute for
      Healthcare Improvement (CBO) is followed in the Southwest region of the
      Netherlands. The guideline states that preoperative hair removal serves no
      purpose in preventing wound infection. DESIGN: Inventory. METHOD: All surgical
      short-stay departments in the Southwest region of The Netherlands received a
      structured questionnaire on their management of preoperative hair removal.
      Questions included whether or not they had a hair removing protocol, which
      methods they used for removing hair and the timeframe within which preoperative
      hair removal usually was carried out. RESULTS: The response was 100% (24/24). The
      majority of surgical short-stay departments did practice preoperative hair
      removal (88%). Less than half of the hospitals use a hair removal protocol. Hair
      clippers were used for preoperative hair removal in most hospitals (86%) and in
      71% the procedure was carried out within 2 hours of the planned operation and
      mostly by nursing staff (71%). No difference was found in hair removal management
      in hospitals with or without a protocol. CONCLUSION: Despite the existence of a
      published guideline that states that preoperative hair removal serves no purpose
      in preventing wound infection, the majority of hospitals in the Southwest region
      of the Netherlands do still carry out the practice as a routine action. The
      policy of hair removal management appears to depend on subjective feelings of
      individual surgeons. The existence ofan evidenced-based guideline does not appear
      to have much effect on this management.

PMID- 18074729
TI  - [A patient with vague inguinal complaints due to a leiomyosarcoma of the inferior
      caval vein].
AB  - A 64-year-old male presented with progressive right-sided inguinal pain radiating
      to the right flank and lower back. He had noticed an infrequent altered
      sensibility on frontal parts of his right upper leg. Physical examination
      demonstrated the presence of a process in the lower abdomen. Computer tomography
      showed a retroperitoneal tumor with a 10 cm diameter that probably originated
      from the inferior caval vein (ICV). During an explorative laparotomy a tumor that
      was compressing the right N. genitofemoralis was radically removed together with
      the right kidney and the ventral wall of the ICV. The histological diagnosis was
      a radically removed leiomyosarcoma. Based on the clinical picture, diagnostic
      imaging and pathologic examination the diagnosis leiomyosarcoma ofthe ICV was
      confirmed. A leiomyosarcoma of the ICV is a rare tumor with atypical
      symptomatology and a slow growth rate often leading to a late diagnosis. Surgery
      is the only effective treatment. The prognosis is moderate.

PMID- 18074730
TI  - [Percutaneous implantation of a pulmonary valve in 3 children with surgically
      corrected cardiac anomalies].
AB  - An 11-year-old girl, a 15-year-old boy and a 12-year-old girl all underwent
      percutaneous implantation of a Melody pulmonary valve prosthesis to replace a
      stenotic and insufficient homograft in the pulmonary artery. Preoperatively, 2 of
      the children suffered from fatigue and dyspnoea on exertion The homografts had
      been implanted between the ages of 1-2, to establish surgical continuity between
      the right ventricle and the pulmonary artery. The anomalies were tetralogy of
      Fallot, pulmonary atresia with intact ventricular septum and pulmonary atresia
      with a ventricular septum defect. Percutaneous pulmonary valve replacement was
      successful in all 3 patients. After implantation, right ventricular pressure
      decreased to 30% of systemic pressure and regurgitation was not observed. All
      patients were discharged in a good condition on the day after the implantation.
      Percutaneous pulmonary valve replacement is a promising technique with good short
      term results. In selected patients this percutaneous technique can substitute or
      postpone the surgical replacement ofa stenotic or insufficient homograft.

PMID- 18074731
TI  - [Spontaneous liver haemorrhage during pregnancy: a rare and life-threatening
      situation].

PMID- 18074732
TI  - [Two pneumococcal vaccines: the 7-valent conjugate vaccine (Prevenar) for
      children up to the age of 5 years and the 23-valent polysaccharide vaccine
      (Pneumo 23) for the elderly and specific groups at risk].

PMID- 18074733
TI  - Insulin resistance and metabolic syndrome in patients with NAFLD but without
      diabetes: effect of a 6 month regime intervention.
AB  - BACKGROUND AND STUDY AIMS: Non-alcoholic fatty liver disease (NAFLD) and the
      metabolic syndrome are two intertwined diseases sharing the same factor in their
      pathogenesis; insulin resistance. The aim of the study was to establish a link
      between glucose tolerance and NAFLD. PATIENTS AND METHODS: Fifty-two non-diabetic
      NAFLD patients were included in the study. Inclusion criteria were elevated
      alanine aminotransferase (ALT), hyperechogenic liver detected at ultrasonography,
      and exclusion of other causes of liver disease. Hepatobiliary ultrasonography and
      laboratory tests including biochemical and metabolic profiles were performed;
      HOMA insulin resistance was calculated. RESULTS: The mean age was 43 years, and
      61% were male. More than a two fold increase in alanine aminotransferase levels
      was seen in 37% of the patients. Serum levels of aspartate aminotransferase,
      gamma-glutamyl transferase, alkaline phosphatase (ALP) were elevated in 36%, 46%,
      and 30% of patients respectively. Low HDL-C levels were found in 46% and high LDL
      C levels in 25%. Other results of note were elevated lipoprotein-a levels in 40%,
      impaired fasting glucose in 23%, impaired glucose tolerance in 26%, elevated
      fasting c-peptide levels in 61%, and elevated fasting serum insulin levels in 11%
      of patients. In 30% of patients, body mass index was over 30 kg/m2 and 78% had a
      waist-hip ratio more than 0.9. HOMA insulin resistance was significantly related
      with elevated ALP levels and hepatomegaly. Following a 6 months treatment with a
      standard diet, liver enzymes and metabolic parameters both improved. Only 7
      patients had persistently high liver enzymes. CONCLUSIONS: Basal insulin levels
      and the oral glucose tolerance test should be an integral part of the evaluation
      of patients with NAFLD. The association between NAFLD and metabolic syndrome as
      well as the benefits of dieting on preventing progression of NAFLD should be
      stressed.

PMID- 18074735
TI  - Acute septic cholelithiasic cholecystitis and adenocarcinoma of the gallbladder;
      an interesting association.
AB  - BACKGROUND AND STUDY AIMS: Primary carcinoma of the gallbladder may present as
      acute lithiasic cholecystitis that leads to severe septic complications. The
      correlation between severe sepsis of the gallbladder and primary carcinoma is
      unclear. The goal of the present study is to examine the relation between severe
      septic complications of lithiasic cholecystitis and primary carcinoma of the
      gallbladder. PATIENTS AND METHODS: A group of 72 patients (22 males, 50 females,
      age range: 45-99, mean age: 68.6 years), with severe septic cholelithiasic
      cholecystitis was treated with emergency surgery after failure of conservative
      treatment, and patients found with primary carcinoma of the gallbladder were
      registered. The resectability and operability of the tumor were studied, as well
      as tumor staging and overall patient survival. RESULTS: During urgent surgery for
      severe septic lithiasic cholecystitis, 12 patients (12/72, 16.6%) were found with
      gallbladder carcinoma. Patients with septic acute lithiasic cholecystitis and
      carcinoma had a higher mean age compared to those without carcinoma (74.8 vs.
      67.4 yrs). Eleven of 12 (91.6%) carcinomas were inoperable, despite resectability
      of 8 out of 12 (66.6%), and overall patient survival was limited to a few months
      after surgery. CONCLUSIONS: Severe septic complications in elderly patients with
      a long-standing history of gallbladder stones may co-exist with primary carcinoma
      of the gallbladder. The percentage of a gallbladder carcinoma detected in septic
      patients reaches up to 16.6%. Even if these patients have a poor general health,
      surgical intervention is a solution when they appear with severe septic clinical
      symptoms caused by gallstones or carcinoma, in order to avoid lethal sepsis. The
      possibility of a carcinoma hidden in the gallbladder must be in mind during
      surgery. Imaging studies before surgery may detect the carcinoma; in most cases
      carcinomas are inoperable, although colecystectomy may be performed during
      surgery.

PMID- 18074734
TI  - Association of the prevalence and grade of steatosis in patients with chronic
      hepatitis C with the host and viral factors.
AB  - AIM: The aim of this study was to investigate the prevalence of hepatosteatosis
      in chronic hepatitis C patients, evaluate the potential impact of some host- and
      virus-related factors on its occurrence and possible influence of steatosis on
      the consequences of hepatitis. PATIENTS AND METHODS: The case records of 387
      patients with hepatitis C and cirrhosis were studied. The prevalence and grade of
      steatosis were investigated and evaluated by logistic regression analysis as
      dependent variable to age, gender, alcohol consumption, body mass index,
      hepatitis C virus (HCV) genotypes, liver enzymes activity, histological activity
      index and fibrosis. RESULTS: Steatosis was found in 47.3% of the patients. It was
      more prevalent in males, alcohol abusers, overweight and obese patients, and in
      those with HCV genotypes 3 and 2. Multivariate analysis confirmed body mass index
      as an independent risk factor for steatosis in the overall patient cohort and in
      those with genotypel without any correlation with the steatosis grade. The
      prevalence and grade of steatosis were associated with alcohol consumption and
      higher fibrosis stage. The age of the patients showed converse association.
      CONCLUSIONS: The male gender, body mass index, alcohol consumption, genotype 2
      and 3 were confirmed as risk factors for hepatosteatosis. Older patients had a
      lesser steatosis grade. The correlation of histological activity index and
      fibrosis scores with the prevalence and higher grade of steatosis suggested a
      possibility to worsen the course of hepatitis C and to accelerate disease
      progression.

PMID- 18074736
TI  - Are humoral factors involved in the colonic mucosal lesion in portal hypertensive
      rats?
AB  - AIMS: With a prehepatic portal hypertensive rat model, we explored the
      involvement of humoral factors to the occurrence of portal hypertensive colopathy
      (PHC), another clinical entity besides portal hypertensive gastropathy (PHG) in
      portal hypertension, by investigating the expression of inducible nitric oxide
      synthase (iNOS), endothelial constitutive NOS (ecNOS), endothelin-1 (ET-1),
      tumour necrosis factor alpha (TNF-alpha) and vascular endothelial growth factor
      (VEGF) in the colonic and gastric mucosa. METHODS: Portal hypertension was
      produced by a two-stage ligation of portal vein plus ligation of the left adrenal
      vein in male Sprague-Dawley rats. Two weeks after complete obstruction of the
      portal vein, the portal pressure was measured and the expression of iNOS, ecNOS,
      ET-1, TNF-alpha and VEGF in the colonic and gastric mucosa were detected by RT
      PCR and immunohistochemistry methods. RESULTS: A 1.8 fold (P < 0.01) elevation of
      the portal pressure was detected in the portal hypertensive rats as compared to
      control. Significantly up-regulation of the mRNA levels of iNOS (P < 0.01), ET-1
      (P < 0.05) and TNF-alpha (P < 0.01), but not ecNOS and VEGF, were detected in the
      colonic mucosa of portal hypertensive rats compared with control. The mRNA of
      iNOS, ecNOS, ET-1, TNF-alpha and VEGF were all significantly increased at varied
      levels in the gastric mucosa as compared to control (P all < 0.05). No difference
      of the appearance and localization of immunostaining of iNOS, ecNOS, ET-1, TNF
      alpha and VEGF in the colonic and gastric mucosa were seen between two groups.
      CONCLUSIONS: These data suggest the involvement of the upregulation of iNOS, ET-1
      and TNF-alpha in the colonic mucosal lesion of portal hypertensive rats.

PMID- 18074737
TI  - Clinical, biochemical and histological correlations in a group of non-drinker
      subjects with non-alcoholic fatty liver disease.
AB  - The correlation between biochemistry, imaging-studies and histology is a matter
      of controversy in non-alcoholic fatty liver disease (NAFLD) and the major
      pathophysiology of non-alcoholic steatohepatitis (NASH) is still unknown. We
      aimed to perform a comparative analysis between clinical, biochemical and
      histological variables of NAFLD. One-hundred and five NAFLD patients (F/M:
      51/54), were studied, all with no-alcohol intake. The groups were followed-up for
      six months. Necroinflammation and fibrosis were more severe in patients with
      diabetes (p = 0.002, and p = 0.0001, respectively). In comparing NAFL to NASH,
      plasma nitric-oxide and malondialdehyde levels were significantly higher (p =
      0.05, for-both), and vitamin-E and-C levels were significantly lower in NASH (p =
      0.002, and 0.001, respectively). The serum ferritin levels were higher in NASH
      patients (p = 0.016). While the ultrasonographic grade was significantly higher,
      the liver-spleen density gradient was significantly lower in NASH group (p =
      0.017, and 0.005, respectively). Within a six month period, serum ALT levels
      dropped into the normal range in 23/76 (30.3%) patients and serum ALT in the 6th
      month correlated significantly with the severity of steatosis, inflammation and
      fibrosis in initial biopsy (p = 0.023, 0.035, 0.011, respectively). In
      conclusion, the probability of severe liver disease is higher in patients with
      elevated-ALT in NAFLD. Serum ferritin levels have some prognostic significance in
      liver damage and fibrosis. Overt diabetes is predictive of advanced fibrosis and
      inflammation. However impaired glucose-tolerance is not. The advice on diet and
      exercise for six months after diagnosis may be a good strategy in NAFLD. The
      patients with normal-ALT without hepatomegaly, morbid-obesity and diabetes seem
      to have a good prognosis, however some of these patients may still require liver
      biopsy.

PMID- 18074738
TI  - Expression of Bax protein in gastric carcinomas. A clinicopathological and
      immunohistochemical study.
AB  - BACKGROUND AND STUDY AIMS: Reduced Bax protein expression has been shown to be a
      negative prognostic factor in patients with breast, ovarian, colorectal,
      esophageal and pancreatic cancer. Our aim was to immunohistochemically study Bax
      protein expression in gastric carcinomas and correlate its expression with
      clinicopathological parameters and prognosis. PATIENTS AND METHODS:
      Immunohistochemistry was performed, using a monoclonal antibody against bax, in
      paraffin-embedded tumor specimens from 47 cases of gastric cancer. RESULTS:
      Positive staining for the Bax protein was found in 20/47 (42.4%) adenocarcinomas
      examined. Negative Bax protein expression in tumour cells was correlated with
      lymph node metastasis (P < 0.05), and degree of differentiation (p < 0.05).
      Univariate analysis showed that the variables with a significant negative impact
      on survival were: high TNM tumour stage, depth of penetration in the gastric
      wall, lymph node involvement, and Bax protein expression. Multivariate analysis
      showed that the only variable with an impact on survival was Bax protein
      expression (p < 0.05, Relative Risk: 3.34). Kaplan-Meier curves showed that the 5
      year survival was 36.8% in cases with positive compared with 16% in cases with
      negative Bax protein expression (p = 0.0427). CONCLUSION: Negative Bax expression
      in gastric cancer is associated with de-differentiation, lymph node metastases,
      and poor clinical prognosis. Bax protein expression might play an important role
      in the development and phenotypic differentiation of gastric carcinomas and tumor
      progression.

PMID- 18074739
TI  - Drug-induced pulmonary toxicity in a patient treated with mesalazine and
      azathioprine for ulcerative colitis.
AB  - We report a case of an 18-yr-old male with high-grade persistent fever,
      productive cough, malaise, diarrhea and associated abnormal findings on chest
      radiography. The patient suffered from ulcerative colitis receiving mesalazine
      and azathioprine. After a further and scrutinized work-up the diagnosis of drug
      induced pulmonary toxicity was made. His condition was improved after
      discontinuing both drugs and the administration of corticosteroids. This is a
      rarely reported case of eosinophilic pneumonia. Although it has not been reported
      previously, the possibility of mesalazine and azathioprine synergism cannot be
      excluded. The clinical, aetiological, diagnostic and therapeutic aspects of the
      disease are discussed demonstrating the paramount importance of bronchoalveolar
      lavage in the diagnosis of this disorder. One should be aware of this entity in
      patients with inflammatory bowel disease.

PMID- 18074740
TI  - Severe hepatitis with prolonged cholestasis and bile duct injury due the long
      term use of ornidazole.
AB  - Nitroimidazole derivatives are commonly used in the treatment of protozoal and
      anaerobic infections, and reports of their hepatotoxicity are rare. We report a
      case of severe hepatitis due to the long-term (8 weeks) use of ornidazole. A 27
      year-old woman presented for evaluation of elevated serum transaminase and total
      bilirubin levels. Liver biopsy revealed portal inflammation, hepatocellular and
      canalicular cholestasis, porto-portal and portocentral bridging fibrosis, and a
      tendency to form nodules. No aetiological factors associated with chronic liver
      disease were identified. The abdominal ultrasonographic findings were compatible
      with chronic liver disease. We therefore made the diagnosis of severe hepatitis
      resulting from the long-term use of ornidazole. We conclude that nitroimidazole
      derivatives may lead to serious liver damage, especially in female patients.

PMID- 18074741
TI  - Cytomegalovirus-associated protein losing gastropathy in an immunocompetent
      adult: a case report.
AB  - Cytomegalovirus infection of the gastro-intestinal tract is frequent and may be
      serious in the immunocompromised patient. We report a case of cytomegalovirus
      infection in an immunocompetent young man who presented total food intolerance,
      pleural effusion and oedema as the result of severe protein losing hypertrophic
      gastropathy. Hypertrophic gastropathy with severe mucosal protein loss has been
      described in Menetrier's disease, a condition of unknown cause which involves
      foveolar hyperplasia of the gastric mucosa. Related hypoalbuminemia is
      responsible for a clinical picture of diffuse edema. In adults, the natural
      course of the disease is marked by a chronic course and carries a bad prognosis.
      In our case, the disease ran a protracted disabling course, likely shortened by
      ganciclovir therapy, followed by slow clinical, endoscopic and biochemical
      resolution after several' months course.

PMID- 18074742
TI  - Cystic fibrosis presenting as diabetes insipidus unresponsive to desmopressin.
AB  - The diagnosis of cystic fibrosis (CF) can be confusing when only a part of the
      typical symptoms is present. In children, CF is usually suspected when dealing
      with chronic pulmonary symptoms (chronic productive cough, recurrent pneumonia or
      bronchiolitis). The pediatric gastroenterologist will exclude CF in all children
      with a meconium ileus, rectal prolaps or a poor weight gain. Atypical CF symptoms
      are hypochloremic alkalosis, recurrent pancreatitis and increased appetite to
      compensate for the pancreatic insufficiency. This case report shows how a
      diagnosis can be delayed when you are mislead by atypical symptoms. It shows the
      importance of looking in napkins and argues for the inclusion of CF in the
      differential diagnosis of polyuria in infants.

PMID- 18074743
TI  - Azathioprine induced colitis: a case report and review of the literature.
AB  - We report a case of an allergic hypersensitivity reaction on azathioprine
      presenting with colitis. Allergic reactions on azathioprine are common in patient
      with inflammatory bowel disease. The clinic of the allergic reaction on
      azathioprine in our patient was atypical in the way it mimicked an acute
      exacerbation of inflammatory bowel disease. The pathogenesis of the allergic
      reaction is still unclear. Although re-challenge can be life-threatening and
      should always be done with precautions, it may definitively proof the causal
      association with the drug and decide for definitive cessation In allergic
      reactions there is no link with TPMT activity but other genetically
      predispositions are proposed.

PMID- 18074745
TI  - Ileoileal intussusception due to an inverted Meckel's diverticulum in a child.

PMID- 18074744
TI  - Takayasu's arthritis associated with chronic hepatitis B.

PMID- 18074746
TI  - An unusual complication of percutaneous endoscopic gastrostomy.

PMID- 18074747
TI  - A man with abdominal bloating: Chilaiditi's syndrome.

PMID- 18074748
TI  - Heterotopic gastric mucosa in the proximal esophagus (inlet patch): a clinical
      entity with increased recognition.

PMID- 18074749
TI  - Endoscopic diagnosis and conservative management of an intramural sigmoid
      haematoma complicating anticoagulant therapy.

PMID- 18074750
TI  - [Nutrition and brain functioning: don't forget to eat!].

PMID- 18074751
TI  - [Discrepancies between the IQCODE (Informant Questionnaire on Cognitive Decline
      in the Elderly) and cognitive test performance].
AB  - OBJECTIVES: The IQCODE is an informant-rated scale of estimated cognitive
      decline. This study examined the scalability of the 16-item form of the IQ-CODE
      and its validity to predict performance on a comprehensive cognitive battery.
      METHODS: The medical files of 169 psychogeriatric day care attendants contained
      an IQCODE. Mokken's nonparametric item response model for polytomous items was
      used to assess the unidimensionality of the IQ-CODE. Tests of orientation,
      episodic memory and executive functioning (Behavioral Dyscontrol Scale, Category
      Fluency, and Expanded Mental Control Test) were administered in order to examine
      predictive validity. RESULTS: Hi-coefficients of scalability for the 16 items of
      the IQCODE ranged from 0.33 to 0.50. Loevinger's H was 0.40 for he full scale,
      which makes it a moderately strong, unidimensional scale. A 'strong' scale (H =
      0.54) was found by selecting a subset of seven items, representing the latent
      construct of problem solving ability. The correlations of the total IQCODE score
      with neuropsychological tests differed significantly from zero but the
      coefficients were quite small, ranging from -0.12 to -0.25. A nonparametric
      optimal discriminant analysis (ODA) was used to derive a cutoff score for the
      IQCODE that would maximize the classification accuracy in differentiating
      patients with comparatively high or low levels of cognitive functioning. Given an
      effect strength for sensitivity (ESS) of 21%, the optimal IQCODE cutoff score
      (3.75) did not reliably discriminate between different levels of cognitive
      ability. More than half of the patients (56%) who were predicted to belong to a
      group of low cognitive ability, in fact performed at a higher level. Conversely,
      overestimation of cognitive ability occurred less often (20%). CONCLUSIONS: In
      this sample of psychogeriatric day care attendants the IQCODE tended to
      underestimate the patient's cognitive scores. In order to understand deficits or
      find remaining competencies, direct assessment of cognitive abilities may be
      preferred to informant based measures.

PMID- 18074752
TI  - [Development of memory clinics in The Netherlands].
AB  - AIM: Memory Clinics (MC's) are multidisciplinary teams involved with early
      diagnosis and treatment of people with dementia. In order to attain more insight
      into the development of this kind of services in The Netherlands, we compared the
      data of two inventories, one of 1998 and the other of 2004. RESULTS: The number
      of MC's increased from 12 to 40. The number of referrals per service has also
      increased. Dementia was the most important syndromal diagnosis. The focus is less
      exclusively on academic centres. An growing number of MC's has structural
      collaborations with local service providers for mental health. Differences among
      MC's exist with regard to the number of referrals per week, the intensity and
      duration of the diagnostic procedures and the proportion of people without
      dementia. There is much interest among MC's to participate in a national network
      for harmonisation and quality control. CONCLUSION: MC's are an increasing part of
      standard care for people with early dementia and other cognitive disorders.

PMID- 18074753
TI  - [Do-not-resuscitate policy on acute geriatric wards in Flanders, Belgium].
AB  - This study describes the historical development and status of a do-not
      resuscitate (DNR) policy on acute geriatric wards in Flanders, Belgium. In 2002
      (the year Belgium voted a law on euthanasia), a structured mail questionnaire was
      sent to all head geriatricians of acute geriatric wards in Flanders (N=94).
      Respondents were asked about the existence, development, and implementation of
      the DNR policy (guidelines and order forms). The response was 76.6%. Development
      of DNR policy began in 1985, with a step-up in 1997 and 200l. In 2002, a DNR
      policy was available in 86.1% of geriatric wards, predominantly with
      institutional DNR guidelines and individual, patient-specific DNR order forms.
      The policy was initiated and developed predominantly from an institutional
      perspective by the hospital. The forms were not standardized and generally lacked
      room to document patient involvement in the decision making process.
      Implementation of institutional DNR guidelines and individual DNR order forms on
      geriatric wards in Flanders lagged behind that of other countries and was still
      incomplete in 2002. DNR policies varied in content and scope and were
      predominantly an expression of institutional defensive attitudes rather than a
      tool to promote patient involvement in DNR and other end-of-life decisions.

PMID- 18074754
TI  - [Consulting the nursing home physician; an interesting but less used option].
AB  - OBJECTIVE: To describe the current use of the consultation function of nursing
      home physicians. Setting Descriptive inventory study. METHODS: A questionnaire
      (with 16 questions regarding the consultation function of nursing home
      physicians) was sent to the head of the medical staff of all nursing homes in The
      Netherlands (n=323). RESULTS: The response to the questionnaire was 78%. The use
      of the consultation function appeared to be very low. Only 20% of respondents
      answered that their medical staff was involved in weekly or monthly consultations
      upon request of general practitioners. Respondents mentioned unfamiliarity with
      the expertise of nursing home physicians as the main reason for this low
      consultation frequency. A positive relationship was found between the
      consultation frequency and some organizational parameters. CONCLUSION: Nursing
      home physicians are not often consulted by general practitioners. Compared to 7
      years ago even a decline in the consultation frequency has occurred.
      Paradoxically, the current trend in chronic care to offer care and treatment as
      long as possible in the home situation of patients, leads to a situation in which
      Dutch nursing homes offer more and more complementary nursing and medical support
      to community care for chronically ill and disabled patients, still living at
      home. This trend stresses also the importance of more collaboration between
      general practitioners and nursing home physicians. Further research concerning
      the added value of this collaboration is necessary

PMID- 18074755
TI  - Forty years of antipsychotic Drug research--from haloperidol to paliperidone-
      with Dr. Paul Janssen.
AB  - The authors describe 40 years of antipsychotic drug research with Dr. Paul
      Janssen, which they have witnessed for a large part from first hand experience.
      The article describes the start of the Janssen Research and its early successes
      with antispasmodics and analgesics. The discovery of haloperidol followed from a
      serendipitous transition from analgesics to antipsychotics and culminated with
      the historical International Symposium on Haloperidol that was held in Beerse
      (Belgium) in 1959. The concept of the central role of dopamine receptor binding
      in schizophrenia has played a decisive part in focusing the Janssen Research on
      antipsychotics. Paul Janssen did not rest with haloperidol (CAS 52-68-8), but
      expanded it into the family of butyrophenone antipsychotics, using Haase's
      handwriting test to clinically characterize the analogues. The emerging
      significance of serotonin antagonism in schizophrenia is discussed in the light
      of the discovery of pipamperone (CAS 1893-33-0), a forerunner of the modern so
      called atypical neuroleptics. Continued research produced a novel chemical family
      of neuroleptics, exemplified by pimozide (CAS 2062-78-4) and fluspirilene (CAS
      1841-19-6), and yielded selective serotonin 5HT2-antagonists. This research
      ultimately led to the discovery of risperidone (CAS 106266-06-2) and paliperidone
      (CAS 144598-75-4), compounds with inbuilt dopamine and serotonin antagonism. The
      authors discuss the lack of inhibition as a common trait of stereotyped behaviour
      in schizophrenia and the means of determining it by means of a computerized
      version of Bente's button press test. Finally the appropriate use of
      antipsychotics for optimal therapeutic result with minimal side effects is
      advocated.

PMID- 18074756
TI  - A synopsis on different homologous series of fomocaine derivatives. In vitro
      interactions with the cytochrome P450 system, toxicity, and local anaesthetic
      effects in rats--part II.

PMID- 18074757
TI  - Synthesis and bioactivity of 6-phenyl-4,5-dihydro-3(2H)-pyridazinone derivatives.
AB  - A series of 6-phenyl-4,5-dihydro-3(2H)-pyridazinone derivatives was prepared and
      examined for cardiotonic activity The structures of these new pyridazinone
      derivatives were confirmed by IR, 1H-NMR and mass spectrum. The cardiotonic
      activities of these compounds were studied on isolated perfused toad heart and
      compared with the activity of levosimendan (CAS 141505-33-1). Compound 5a emerged
      as the mostinteresting compound in this series with potential cardiotonic
      activity.

PMID- 18074758
TI  - Clinical study on the effect of simvastatin on paraoxonase activity.
AB  - Human paraoxonase (PON1) is a serum high-density lipoprotein-associated
      phosphotriesterase. High-density lipoprotein (HDL) plays the role of a carrier
      and the site of action of this enzyme. According to a majority of authors, PON1
      acts as an antioxidant, preventing low-density lipoprotein (LDL) peroxidation.
      However, due to the fact that in vivo serum PON1 is predominantly associated with
      HDL, its major physiological role might be to protect HDL, rather than LDL, from
      oxidation. Nevertheless, the physiological substrate of PON1 still remains to be
      discovered. The objective of this study was to determine changes in PON1 activity
      during treatment with simvastatin (CAS 79902-63-9, Lipex) in patients with type
      IIa and/or IIb hyperlipoproteinemia. PON1 activity was assessed in 32 patients
      with hyperlipoproteinemia type IIa or IIb with an LDL cholesterol concentration
      higher than 4.2 mmol/l. Patients received simvastatin in a daily dose of 20 mg.
      The lipid status and PON1 activity were assessed at baseline, as well as 3 and 6
      months after the beginning of treatment. The study demonstrated a statistically
      significant lipid lowering effect of simvastatin on total and LDL cholesterol,
      and an increase in PON1 activity in patients with both types of
      hyperlipoproteinemia. No statistically significant correlation was observed
      either between changes in PON1 activity and HDL, HDL2, HDL3 and LDL cholesterol
      and triglyceride levels, or between their first differences in patients with both
      type IIa and IIb hyperlipoproteinemia. The obtained results suggest that the
      antioxidant properties of simvastatin might be caused by a mechanism independent
      of apoAI-containing lipoprotein concentration. The antioxidant properties of
      simvastatin, which play an important role in HDL protection from oxidation, could
      be the mechanism inducing the increase in PON1 activity.

PMID- 18074759
TI  - Effect of intravenous esomeprazole 40 mg and pantoprazole 40 mg on intragastric
      pH in healthy subjects. A prospective, open, randomised, two-way cross-over
      comparative study.
AB  - OBJECTIVE: The aim of this study was to compare the effect on intragastric
      acidity over 24 h on days 1 and 3 following treatment with intravenous (i.v.)
      esomeprazole 40 mg (CAS for esomeprazole sodium: 161796-78-7) and pantoprazole 40
      mg (CAS for pantoprazole sodium: 138786-67-1). METHODS: In an open, randomised,
      two-way cross-over study, 36 healthy volunteers received esomeprazole (Nexium) 40
      mg or pantoprazole 40 mg, both administered once daily as an i.v. bolus injection
      for 3 consecutive days. Continuous 24-h pH recordings were made under
      standardised conditions at baseline and on days 1 and 3 of each treatment period.
      The primary variable was the percentage of time with intragastric pH > 4 during a
      24-h period. RESULTS: Time with intragastric pH > 4 was significantly greater
      with esomeprazole than with pantoprazole during the first 4 h (47.8% vs. 18.9%),
      as well as for the 24-h period of day 1 and day 3 (day 1: 38.8% vs. 23.7%; day
      3:55.0% vs. 35.2%, p < 0.0001 for all times examined). Mean of median
      intragastric pH with esomeprazole was significantly higher than with pantoprazole
      during the 24-h period (day 1:3.2 vs. 2.2, p < 0.0001; day 3: 4.3 vs. 3.1, p <
      0.00001). CONCLUSION: Esomeprazole administered as a 40 mg i.v. bolus injection
      provided faster and more effective control of intragastric acidity than a 40 mg
      i.v. bolus injection of pantoprazole, and also maintained pH > 4 longer both
      during the first 4 h on day 1 and during the 24-h period of day 1 and day 3 of
      dosing.

PMID- 18074760
TI  - Development of an ultra-performance liquid chromatography technique coupled with
      mass spectrometry for the measurement of tacrolimus in micro-samples of whole
      blood, and its application on a pharmacokiinetic trial.
AB  - OBJECTIVE: The aim was to develop a rapid, specific, sensitive and accurate
      chromatographic technique coupled with mass spectrometry for the measurement of
      tacrolimus (CAS 104987-11-3) in microsamples of whole blood, and its application
      on a pharmacokinetic pilot trial. METHODS: A fast gradient was designed in an
      ultra-performance liquid chromatography, and coupled with a mass spectrometer for
      the quantification of tacrolimus in 100 microl samples of EDTA whole blood.
      Multiple reaction monitoring was used for the measurement of tacrolimus (m/z(+1)
      821.49-->4768.35 Th) and sirolimus as internal standard (m/z(+1) 931.69-->864.39
      Th). The method was validated according to Mexican regulatory guidelines. Twenty
      four young healthy male volunteers with similar hematocrit values participated in
      the pharmacokinetic trial; an oral single dose of one 5 mg tacrolimus capsule was
      administered and kinetic profiles were described since 0 h until 24 h post-dose.
      RESULTS: Method showed to be accurate, precise and linear over the range from 1
      to 80 ng/ml, having an absolute recovery of 94%. Molecule was stable for two
      months at -70 degrees C, and heparin interfered with its quantification. Total
      run-time is around 1.5 min. Mean maximum blood concentration was 32.63 +/- 1.74
      ng/ml, and was reached at 1 h post-dose; elimination half-life was 14.18 +/- 5.71
      h. CONCLUSIONS: Method developed is not time-consuming, inexpensive, and
      sensitive enough for its application during pharmacokinetic trials, and can be
      suitable for therapeutic drug monitoring in transplanted patients.
      Pharmacokinetic data obtained in Mexican population are quite similar to
      previously reported in international literature.

PMID- 18074761
TI  - Prospective controlled cohort studies on long-term therapy of ovairian cancer
      patients with mistletoe (Viscum album L.) extracts iscador.
AB  - BACKGROUND: Mistletoe extracts such as Iscador are commonly used as
      complementary/anthroposophic medications for many cancer indications,
      particularly for solid cancers. The efficacy of this complementary therapy is
      still controversial. OBJECTIVE: Does long-term therapy with mistletoe extracts
      Iscador show any effect on survival and psychosomatic self-regulation of patients
      with ovarian cancer? PATIENTS AND METHODS: Prospective recruitment and long-term
      follow-up in controlled cohort studies. (1) Two randomized matched-pair studies:
      OvarRand (ovarian cancer patients without distant metastases; 21 pairs) and
      OvarMetRand (ovarian cancer patients with distant metastases; 20 pairs); patients
      having no mistletoe therapy were matched for prognostic factors. By paired random
      allocation, one of the patients of each pair was suggested therapy with mistletoe
      extracts Iscador to be applied by her attending physician. (2) Two non-randomized
      matched-pair studies: Ovar (ovarian cancer patients without distant metastases;
      75 pairs) and OvarRand (ovarian cancer patients with distant metastases; 62
      pairs); patients that already received therapy with mistletoe extracts Iscador
      were matched by the same criteria to control patients without therapy with
      mistletoe extracts Iscador. RESULTS: For overall survival in the randomized
      studies, the effect in favor of therapy with mistletoe extracts Iscador was
      significant in OvarMetRand but not in OvarRand; hazard ratio estimate and 95%
      confidence interval: 0.40 (0.15, 1.03) and 0.33 (0.12, 0.92), respectively. In
      the non-randomized studies Ovar and OvarMet, the results adjusted for relevant
      prognostic variables were 0.47 (0.31, 0.69) and 0.62 (0.37, 1.05). Psychosomatic
      self-regulation in the Iscador group increases significantly within 12 months on
      a scale from 1 to 6 compared with the control group in the randomized study
      OvarRand as well as in the non-randomized study Ovar on patients with ovarian
      cancer without distant metastases; estimate of the median difference and 95%
      confidence interval: 0.58 (0.30, 0.90) and 0.30 (0.05, 0.65), respectively.
      CONCLUSION: Mistletoe extracts Iscador might have the effect of prolonging
      overall survival of ovarian cancer patients. In the short term, psychosomatic
      self-regulation increases more markedly under Iscador therapy than under
      conventional therapy alone.

PMID- 18074763
TI  - Positioning nursing and midwifery research for the future: external & internal
      challenges.

PMID- 18074764
TI  - Current issues in mental health service provision in Australia.

PMID- 18074762
TI  - Bioequivalence study of a fixed dose combination of nitazoxanide and ofloxacin in
      Indian healthy volunteers.
AB  - OBJECTIVE: The pharmacokinetics of nitazoxanide (CAS 55981-09-4) and ofloxacin
      (CAS 82419-36-1) has been extensively evaluated in adult human volunteers
      individually after oral administration of tablet formulation. However, no
      published data is available regarding the combined pharmacokinetics and
      bioavailability of this particular fixed dose combination. In light of the above,
      a clinical study was designed to evaluate the bioequivalence of two fixed dose
      combination (FDC) products of two manufacturers containing nitazoxanide 500 mg
      and ofloxacin 200 mg in healthy Indian male volunteers. METHODS: 24 healthy male
      volunteers (age 25 +/- 4.6 years; weight 74.5 +/- 7.87 kg) were enrolled in this
      study. Each subject received a Test fixed dose combination and a Reference fixed
      dose combination formulation in a randomized, single dose, fasting state, two
      period, crossover study design with a 1-week washout period between the doses.
      Extraction of the drugs from the plasma was carried out by precipitation method.
      Analysis of tizoxanide (active metabolite of nitazoxanide) and ofloxacin from
      plasma samples was done by a simple and sensitive HPLC method using UV detection
      developed in our laboratory. An analysis of variance was performed on the
      pharmacokinetic parameters Cmax, AUC(0-t), AUC(0-infinity). using general linear
      model (GLM) procedures in which sources of variation were subject, formulation,
      period. RESULTS: The results of this investigation indicated that there were no
      statistically significant differences between the two products in either the mean
      concentration-time profiles or in the obtained pharmacokinetic parameters. 90 %
      confidence limits for the log-transformed data of Cmax, AUC(0-t), AUC(0-infinity)
      were within the acceptable range of 0.80-1.25. CONCLUSION: Thus, these findings
      clearly indicate that the two products are bioequivalent in terms of rate and
      extent of drug absorption. Both the preparations were well tolerated with no
      adverse reactions seen throughout the study.

PMID- 18074765
TI  - Deconstructing nursing practice: a reflective process.
AB  - The literature tells us that reflection offers a means to evaluate practice and
      to identify learning from our practice experiences. The following description of
      a practice incident will be discussed loosely in the light of Rolfe's 'Model of
      Nursing Praxis' as a means of exploring the theoretical exercise of 'reflection'
      within a proposed theoretical framework. It is hoped that the exercise will help
      to achieve some of the suggested positive endpoints of reflection, and provide
      insight and learning on an incident that was particularly powerful on both a
      personal and a professional level.

PMID- 18074766
TI  - The nocebo effect for women in waiting.
AB  - This paper, drawn from a larger phenomenological study, critiques the effects of
      "waiting" for women when they have an abnormal Pap test result. The hurt and
      injury incurred by women who perceive they have no choice but to become patient
      waiters in a health system that seemingly values the time of the health care
      provider over the health care recipient is discussed. These iatrogenic,
      unintended, harmful consequences are referred to as the nocebo effect. The
      participants provide the principal voices and their stories are dialogued to a
      lesser degree with the literature and the discourse of critical theorists who
      question power relationships in health professional practice. The purpose of this
      paper is served when the women's stories strip away some of the taken-for
      granted, invisible aspects of the health professional's power.

PMID- 18074767
TI  - Yaitya tirka madlanna warratinna: exploring what sexual health nurses need to
      know and do in order to meet the sexual health needs of young Aboriginal women in
      Adelaide.
AB  - Young Aboriginal women are consistently identified as having poorer health
      outcomes and access to sexual health services than non-Indigenous Australians.
      Yet the literature is particularly silent on what sexual health nurses need to
      know and do in order to work well with young urban Aboriginal women. This paper
      reports on a qualitative pilot study undertaken by a non-Indigenous nurse in
      Adelaide. The participatory action research methods used in this study were
      sensitive to the history of problems associated with research in Aboriginal
      communities. A reference group of Elder Aboriginal women and Aboriginal health
      workers guided all aspects of the study. A partnership approach between the
      researcher and the Reference Group ensured that the methods, analysis, and final
      report were culturally safe. Three groups participated in this study: Elders and
      Aboriginal health workers; young Aboriginal women, and sexual health nurses. All
      participants acknowledged the importance of nurses being clinically competent.
      However, the overarching finding was a lack of a clear model of cultural care to
      guide health service delivery. Three interrelated themes emerged from the data to
      support this contention. These were: the structural and personal importance of
      establishing and maintaining trustworthy relationships between nurses, Aboriginal
      health workers and Elders; the recognition that Aboriginal culture does exist,
      and is important in urban areas; and the importance of gender considerations to
      understanding urban women's health business. A partnership approach was
      recommended as a way to use these findings to develop a transparent cultural
      model of care. Further research is currently being undertaken to progress this
      agenda.

PMID- 18074768
TI  - Practical problems for Aboriginal palliative care service provision in rural and
      remote areas: equipment, power and travel issues.
AB  - With regards to end-of-life care, there is scant published research that looks
      specifically at the provision of palliative care services for Indigenous people.
      In addition, for Indigenous people in the rural and remote areas there is only
      limited literature that focuses on the problems associated with geography. To
      address the hiatus in the literature on Aboriginal, rural and remote palliative
      care, the following article provides findings from a two-year research project,
      funded by Australia's National Health and Medical Research Council (NH&MRC),
      which developed an innovative model for Indigenous palliative care. The data was
      collected through a qualitative methodology (descriptive phenomenology) which
      involved open-ended in-depth interviews, audio-recorded, transcribed verbatim and
      thematically analysed. The sub-set of findings from the study presented in this
      paper examine issues in relation to the many practical obstacles in relation to
      palliative care service provision to Indigenous people in the rural and remote
      areas. The findings are a testament to the ingenuity and dedication of those who
      provide end-of-life care for Aboriginal peoples in rural and remote locations.
      The information about the many obstacles associated with equipment, power,
      transport, distance and telephone access provide important insights to inform the
      development of health policy planning and funding. The topic is specifically
      relevant to nurses as further findings from the study indicate that clinic and
      community nurses are key health professionals providing care to Indigenous people
      in the rural and remote areas.

PMID- 18074769
TI  - Culturally diverse Malayan milieu: experiences and perceptions of RAANC nurses
      1955-1960.
AB  - The war exploits of Australian Army nurses have been represented in a number of
      literary sources, but there is a paucity of data about the nurses who served in
      the Malayan Emergency (1948-1960). Using descriptive interpretive historiography,
      with a central focus on oral testimony, this paper aims to highlight the
      culturally rich and diverse environment of Malaya in the 1950s. Semi-structured
      interviews were conducted with four women from the Royal Australian Army Nursing
      Corps to expose their experiences and perceptions of the Malayan environment and
      its people. The information provided by these nurses was subjected to manual
      thematic analysis resulting in the emergence of a number of themes. One prominent
      theme, Malaya's cultural diversity, was chosen for this paper because it
      contained an abundant source of new and rich data. To protect the identities of
      the informants pseudonyms were used in the presentation of the oral narratives.
      This approach led to revelations about how Australian women, with limited
      knowledge or exposure to other cultural groups, engaged in work and leisure time
      pursuits in Malaya's exotic cultural milieu.

PMID- 18074770
TI  - [Cellular aspects of hypertrophic cardiomyopathy pathogenesis: the role of
      cardiomyocyte polyploidy and activation of the proliferating cell nuclear antigen
      in the myocardium].
AB  - Mechanisms of hypertrophy development in hypertrophic obstructive cardiomyopathy
      (HOCM) have not been enough investigated. In our study, there have been examined
      patients with severe HOCM at different ages, including children, and patients
      with essential arterial hypertension (EAH). There was found, that HOCM in
      children compared to adults was characterized by considerable interventricular
      septum (IVS) hypertrophy and it was accompanied by the acceleration of
      cardiomyocyte polyploidy. The average ploidy level of cardiomyocytes in children
      with HOCM was higher than analogous indices in adults. The average ploidy level
      of nuclei, the part of PCNA-positive nuclei and polyploidic nuclei of
      cardiomyocytes in aduls with HOCM were authentically higher than in patients with
      EAH. Activation of the nuclear antigen in stromal cells was detected only in
      patients with HOCM. Our findings provide evidence of an important role of
      cardiomyocyte polyploidy and activation of the proliferating cell nuclear antigen
      in development of the myocardial hypertrophy in patients with HOCM.

PMID- 18074772
TI  - [Endocellular regulation of oxygen consumption in the neurone of isolated
      crawfish stretch receptor].
AB  - Morphological correlations of functional regulation of oxygen consumption have
      been investigated in single of isolated crustacean stretch receptor neuron. The
      increase in oxygen consumption is promoted by: 1) redistribution of mitochondria
      and increase in cytochrome oxidase (CO) activity in mitochondria near to the
      plasmatic membrane; 2) coordination of mitochondria aggregation rhythms with pO2
      rhythms in external environment of a cell; 3) reduction of the area with high CO
      and mitochondria activity, and reduction of the way of oxygen diffusion; 4)
      increase in CO activity gradient from periphery to the center of the neuron body;
      5) carry of oxygen by water current under hydration of the neuron body, and
      cytoplasm dilution under transition of a part of gel in sol; 6) cyclic changes in
      the neuron body and hillock sizes ratio determining carry of oxygen by water
      current into the neuron body, oxygen absorption by mitochondria in the neuron
      body, and transition of the water released from oxygen from the neuron body into
      hillock and further into the external environment.

PMID- 18074771
TI  - [Cytological study of the kidney ischemic lesions in rats].
AB  - The course of reparative regeneration after 5/6 nephrectomy and use of low-dose
      radiation has been studied by means of light and electron microscopy. The
      experiments were performed on 30 male Wistar rats. All animal procedures were
      conducted after approval of the protocol by the animal Studies Ethics Committee
      of the University of Tartu. Renal ablation was then accomplished by right
      nephrectomy and selective ligation of extrarenal branches of the left renal
      artery such that approximately 2/3 of the left kidney was infracted. All together
      30 rats were randomised after the surgery and divided into two groups matched for
      age and body weight at week 0 and studied during 2, 4 and 8 weeks: groups I
      (nephrectomized, n = 15), groups II (nephrectomized and irradiated, n = 15). Left
      kidney of II groups rats was irradiated (60Co) 24 h after surgery in
      anaesthetized (Brietal) animals with 3 Gy in a single dose. As a result of
      experimentally induced ischemia destruction of renal corpuscles, perishing of
      tubular epithelial cells and and proliferation of connective tissue is followed.
      Reparative regeneration is based on aseptic inflammation, duration of its phases
      depends on the extent of organ impairment. In nephrectomized rats parallel to
      reparative regeneration, necrosis and deposition of calcium is found in the
      cortical substance. Calcium plays important role in kidney metabolism and its
      increased content is characteristic to degenerative changes. The experiments
      reveal that use of low-dose radiation does not accelerate process of reparative
      regeneration in rat kidney.

PMID- 18074773
TI  - [Effect of hydrogen peroxide on ability of neutrophils to generate the reactive
      oxygen and chlorine species and secrete myeloperoxidase in vitro].
AB  - The influence of H2O2 at concentrations of 10(-8)--10(-2) mol/l on neutrophil
      ability to generate the reactive oxygen and chlorine species (ROCS) and secrete
      myeloperoxidase (MPO) was studied, and H202 injurious effect on neutrophils was
      also investigated in this work. It was revealed that H2O2 at concentrations of 2
      x 10(-3)--2 x 10(-2) mol/l induced disturbance of the neutrophil membrane barrier
      properties and lactate dehydrogenase release. The incubation of the neutrophils
      with the addition of 10(-4)--10(-7) mol/l H2O2 led to an increase in the cell
      ability to generate ROCS during phagocytosis and decreased neutrophil ability to
      secrete MPO and ROCS in extracellular medium during adhesion. The mechanisms of
      H2O2 effect are coupled with arachidonic acid metabolism. Inhibition of metabolic
      pathways of 5-lipoxygenase or cyclooxygenase increased the destructive effect of
      H2O2 on the cells. Five-lipoxygenase way prohibition led to cancellation of H2O2
      influence on MPO and ROCS secretion and to enhancement of H2O2 effect on
      neutrophil ability to generate ROCS during phagocytosis. The data obtained
      testify to the high neutrophil resistance to destructive effect of H2O2 and
      confirm the regulatory role of H2O2 with respect to the neutrophil functions.

PMID- 18074774
TI  - [Morphometric structure of thyroid and adrenal glands in bulls under different
      modes of adaptive technology].
AB  - This work was carried out to study dynamics of morphometric structure of thyroid
      and adrenal glands in bulls brought up in early postnatal ontogenesis at lowered
      (-4.4-(-)8.0 degree centigrade) and raised (8.7-20.5 degree centigrade)
      environment temperature with further grow and fattening using intensive
      technology with application of new biogenic matters. For the first time it has
      been experimentally proved the expediency of correction of morphometric structure
      of investigated endocrine glands in bulls under condition of joint application of
      Suvar with Polistim or with DAFS-25 during the various periods of postnatal
      ontogenesis. Special features of morphometric structures of the thyroid glands
      (diameter, the area of follicles, thickness of thyroid epithelium, follicles
      index) and the adrenal glands (weight, width of zones of cortical and brain
      substances, the areas of cells and nuclei, and nuclear cytoplasmic ratio) in
      animals maintained under condition of adaptive technology have been investigated.
      It has been established that the endocrine glands morphometric parameters in
      bulls brought up at both lowered and raised temperature are more relief under
      combined effect of Suvar and DAFS-25 than Suvar and Polistim.

PMID- 18074775
TI  - [Determination of quantitative parameters of Escherichia coli phagocytosis by
      mouse peritoneal macrophages].
AB  - The fluorometric method was used to study guantitative parameters of phagocytosis
      of fluorescein-labeled Escherichia coli cells by mouse peritoneal macrophages. E.
      coli cells were conjugated with fluoresceinisothiocyanate (FITC) and then
      incubated with macrophages. At the end of the assay phagocytosis was arrested
      with a lysing solution (0.5% Triton X-100 in 0.01 M phosphate-buffered 0.15 M
      saline, pH 7.4). Trypan blue at a concentration of 0.04% was used as a quenching
      agent to differentiate between attachment and ingestion of E. coli cells. The
      time course analysis within this method showed that phagocytosis of E. coli cells
      was temperature and opsonin dependent. The number of E. coli cells ingested by
      macrophages increased rapidly during the initial 60 min of incubation at 37
      degrees C. E. coli cells required opsonization with 5% native serum to achieve
      their optimal uptake. The uptake of nonopsonized bacteria by macrophages was
      significantly lower that that of opsonized ones (P < 0.05). It was demonstrated
      that sodium azide inhibited phagocytosis of E. coli cells by mouse peritoneal
      macrophages in a dose-dependent manner.

PMID- 18074777
TI  - [Cortical cytoskeletal ring in prophase II leads to correction of abnormalities
      of the first meiotic division and to meiotic restitution of pollen mother cell
      nucleus].
AB  - The deviation of prophase cytoskeletal ring formation was determined during
      meiotic division in 50% of pollen mother cells (PMCs) in maize haploid No 1498
      (Zea mays). At prophase in both meiotic divisions the cytoskeletal ring is formed
      in cortical region of cytoplasm instead of perinuclear. Sometimes formation of
      both perinuclear and cortical rings is observed in the same cell. It has been
      shown that in multinucleate PMCs the cortical ring leads to the consolidation of
      chromosomes into common spindle and to meiotic restitution.

PMID- 18074776
TI  - [The effect of phosphatidylinositol kinase inhibitors on store-dependent Ca2(+)
      transport in macrophages].
AB  - Using Fura-2AM microfluorimetry the role of phosphatidylinositol kinases in the
      regulation of Ca2+ signals induced by purinergic agonist ATP and endoplasmic
      Ca2(+)-ATPase inhibitor thapsigargin in rat peritoneal macrophages was
      investigated. It was shown that two structurally distinct phosphatidylinositol 3-
      and phosphatidylinositol-4-kinases inhibitors wortmannin and LY294002 showed a
      dose- dependent effect on store-dependent Ca2(+)-entry, induced by thapsigargin
      or ATP. The data suggest that phosphatidylinositol 3- and phosphatidylinositol-4
      kinases play an important role in the activation of store-dependent Ca2(+)-entry
      in macrophages and that their effect might be mediated by their influence on
      actin cytoskeleton. The results are compatible with the "secretion-like coupling
      model" for store-dependent Ca2(+)-entry in macrophages based on a reversible
      trafficking and coupling of the Ca2+ store with the plasma membrane which
      suggests the involvement of microfilaments and phosphatidylinositol kinases.

PMID- 18074778
TI  - [Characteristics of the cytomixis in the pollen mother cells of transgenic
      tobacco plants (Nicotiana tabacum L.) with mutant phenotype].
AB  - This paper represents the frequency characteristics and cytological analysis of
      cytomixis in the course of male meiosis in transgenic tobacco plants (Nicotiana
      tabacum L.) with altered flower morphology and male sterility. The influence of
      cytomixis on qualitative composition of the meiotic products is shoron
      (cytoplasts and polyads formation). It was established that doubling of
      chromosomes number increased cytomixis frequency in the investigated plants.

PMID- 18074780
TI  - [Ultrastructural basis of biotrophic relationships between brown rust fungus and
      common wheat].
AB  - The ultrastructural research of relationships between common wheat and brown rust
      fungus Puccinia triticina demonstrated that the biotrophy was based on the
      induction of plant cytoplasmic aggregate organization, nuclear migration to
      haustorium and stimulation of mesophyll cell metabolism. Resistant reactions in
      the form of hypersensitivity and depositions on plant cell walls were suppressed
      up to fungal sporogenesis. Cytoplasmic reorganization and nuclear taxis to
      haustorium were not registered in the epidermal and vascular bundle sheath cells.

PMID- 18074779
TI  - [The role of microtubular cytoskeleton and callose walls in the cytomixis process
      in tobacco (Nicotiana tabacum L.) pollen mother cells].
AB  - We have studied the microtubule cytoskeleton structure and callose walls
      deposition in the course of meiosis at the cytomictic and normal tobacco (N.
      tabacum L.) PMCs. It was ascertained that microtubule cytoskeleton did not play
      an evident part in the process of cytomixis. Increased cytomixis frequency
      probably is determined by irregular callose walls deposition. The possible
      reasons of nuclear material passage between tobacco PMCs at the cellular level
      are discussed.

PMID- 18074781
TI  - [Kinetics of proliferation, differentiation and transcription of genes regulating
      apoptosis in cultured human BCR/ABL+ Ph+-cells].
AB  - Ph+, bcr/abl+ cells arise due to t(9,22) chromosome translocation and Ph+
      chromosome formation in hematopoietic stem cells. The cells show appreciable
      apoptosis suppression but retain their ability to differentiate and maturate. Ph
      chromosome, bcr/abl oncogene and Ph+, bcr/abl+ cells themselves are the hallmark
      of chronic myeloid leukemia. Under leukemia progression differentiating Ph+,
      bcr/abl+ cells transform into leukemic malignant cells with differentiation
      block. It is assumed to be a result of subsequent mutations or activation of
      proliferation of long silent Ph+ cells arisen previously in the stem cells
      because of the translocation. Real mechanism underlying the cell transformation
      remains unknown. This work was performed to develop a proper cell model allowing
      us to study functioning of differentiating Ph+, bcr/abl+ cells and their real
      transformation into malignant cells with block of differentiation. For this
      purpose we have investigated kinetics of Ph+, bcr/abl+ cells proliferation,
      differentiation, cell death and transcription of antiapoptotic genes in cultured
      14-day of Ph+ mononuclear cells isolated from peripheral blood of a patient in
      chronic phase of chronic myeloid leukemia before treatment. The results obtained
      revealed that Ph+ cell differentiation proceeded in accord with characteristic
      scheme of chronic myeloid leukemia in vivo. Myeloid cells of hematopoietic cell
      lineage amounted to 3/4 of live Ph+ mononuclear cells undergoing accumulation and
      subsequent consumption in the course of differentiation. 95% myeloid cells were
      differentiating Ph+ granulocytes. The most deal of differentiating Ph+ cells was
      myelocytes. The rate ratio of myelocyte accumulation to its subsequent
      consumption showed that the rate of transformation into metamyelocytes was
      significantly decreased at this differentiation stage. Ph+ cells cultivation
      curves characterized cell death at different differentiation stages. There were
      observed the cell death of proliferating Ph+ cells and Ph+ myelocytes, and
      intensive death of mature cells as well. P/D index, that is ratio of immature Ph+
      granulocytes differentiated by cell dividing (blasts, promyelocytes and
      myelocytes) to the cells differentiated without dividing (metamyelocytes and
      mature neutrofiles), revealed active of proliferation at the beginning of
      cultivation and unexpected new proliferative activity at the end of cultivation
      in the presence of growth factor. The peaks of antiapoptotic bcr/abl gene
      transcription activity coincided with the observed active proliferation at the
      beginning and at the end of cultivation. Cell proliferation, differentiation and
      apoptosis were noticeably accelerated by growth factor treatment. Thus, the study
      of the Ph+ cells cultivation kinetics is rather informative approach to
      investigation of continuous regulation of cellular and molecular processes in
      vitro in the case of chronic myeloid leukemia and allows more complete
      consideration of Ph+, bcr/abl+ cells hematopoiesis.

PMID- 18074782
TI  - [Seasonal variability of the karyotype structure of Chironomus plumosus (Diptera,
      Chironomidae) from a biotope of Kaliningrad].
AB  - Chironomus plumosus larvae from the polluted Shkolnoe lake, Kaliningrad, have 2n
      = 8 and 2n = 8 + B. In winter season we found 11 types of hetero- and homozygous
      inversions in A, B, C, D, E, and F arms whereas in summer season we registered 7
      types of the same inversions in A, B, C, D, and E arms. All inversions with
      exception of the inversion in arm C correspond to Hardy-Weinberg equilibrium. The
      arm IVG shows homozygous increase of centromeric heterochromatin more frequently
      in summer than in winter (34.4% as compared with 1.8%). The arm E has asynapsis 2
      times less frequently in summer than in winter (21.4% as compared with 44.6%).

PMID- 18074783
TI  - [Localization of human brain areas activated for chaotic and ordered pattern
      perception].
AB  - The aim of our work was to localize cortical areas involved in the processing of
      incomplete figures using functional MRI (fMRI) for 8 healthy volunteers (18-30
      year old) with the did of anatomical and fMRI fast imaging technique: echo planar
      imaging (EPI), whole brain scan (36 slices) matrix 64 x 64, 3.7 second. We used
      1.5 T MR-scanner and BOLD-method (Blood Oxygenation Level Dependent), based on
      distinctions of magnetic properties of hemoglobin. Fast imaging technique on
      modern MR-scanners with > or = 1.5 T provides precise statistical maps of
      oxygenation increase with high spatial resolution. For test stimuli we used
      matrix of Gabor grating. We used two types of 10 x 10 matrices with chaotic and
      ordered orientation of Gabor gratings. The size, brightness and contrast of the
      stimuli were identical. The chaotic and ordered patterns activated different
      brain areas. We establish that ordered patterns activated only primary visual
      cortex - V1 and V2, (BA17-18), wheareas chaotic patterns activated in addition
      primary visual cortex, the V3,V4,V5 (BA19) of the occipital cortex and the area 7
      of parietal area (BA7) classification. Decision making for that task is localized
      in prefrontal and frontal cortex, including (BA 6, 9, 10).

PMID- 18074784
TI  - [Selective disturbance of associative memory reactivation by serotonin or NMDA
      glutamate receptor antagonists in snail].
AB  - Effects of serotonin or glutamate receptors antagonists on reactivation of food
      aversion conditioning were studied in snail Helix lucorum. Metiotepin
      (nonselective serotonin receptor antagonist, 0.1 mg/snail) or MK-801 (NMDA
      glutamate receptor antagonist, 0.005 mg/snail) were injected 24 hours after 3
      days of food aversion conditioning, then reminding stimulus (banana,
      "conditioned" food) was presented and food aversion conditioning was tested. Long
      term impairing (more then 2 weeks) of food aversion conditioning was found 3
      hours after concurrent reminding and inhibitors injection. Injection of receptor
      antagonists without reminding stimulus did not influence on food aversion
      conditioning retrieval. Besides, in snails with amnesia after
      metiotepin/reminder, facilitation of repeated elaboration aversion conditioning
      on banana is revealed. The repeated training of snails with amnesia caused by MK
      801/reminder did not result in food aversion conditioning. It is was suggested
      that 5-HT5,6,7 serotonin receptors are involved in mechanisms of memory "trace"
      extraction of food aversion conditioning, whereas NMDA glutamate receptor - in
      processes of its storage in snail.

PMID- 18074785
TI  - [The role of skin afferent in regulation of locomotion evoked by electrical
      epidural stimulation of spinal cord in decerebrated cats].
AB  - The role of hindpaw skin afferent input in the locomotor pattern formation
      induced by epidural spinal cord stimulation was investigated in decerebrated
      cats. Locomotor activity was evoked by continuous 3-5Hz stimulation of dorsal
      surface of L4-L5 spinal segments. Kinematic and electromyographic activity (EMG)
      of m. Quadriceps, m. Semitendinosus, m. Tibialis anterior an m. Gastrocnemius
      lateralis before and after blocking of skin receptors in one hind limb were
      recorded. In addition, reflex responses in the hind limb muscles to epidural
      stimulation with frequency 0.5 Hz were analysed. Blocking of skin receptors of
      the foot with chlorothane paw irrigation or 2 % lidocaine administrated into the
      hind paw was performed. After blocking of skin receptors of the foot the stepping
      pattern changed. Stepping with dorsal foot placement and dragging during swing
      phase was observed. Duration of stance phase significantly decreased. Inhibition
      of polysynaptic activity of proximal and distal extensor muscles and distal
      flexor muscles of hind paw during locomotion was found. Monosynaptic responses
      after blocking of skin receptors of the foot changed insignificantly.

PMID- 18074786
TI  - [Sequence of ventricular repolarization under body cooling in the frog].
AB  - Lowering the temperature is known to prolong the repolarization of
      cardiomyocytes. However, whether the prolongation of action potentials is uniform
      throughout the myocardium, and whether this prolongation is obvious in ECG,
      remains unclear. Ventricular repolarization sequences and body surface potential
      distributions were studied in 20 frogs Rana temporaria using epicardial and body
      surface potential mapping. An apex-to-base ventricular repolarization sequence
      corresponded to the distribution of local repolarization durations was
      demonstrated at the temperature of 18 degrees C. The body surface potential
      distribution during the ST-T complex was characterized by the cranial negative
      and caudal positive potential areas. Under the body cooling to 10 degrees C,
      repolarization prolonged to a greater extent at the apex that resulted in the
      base-to-apex repolarization sequence, which, in turn, caused an inversion in the
      body surface potential distribution with cranial portion of the body being
      positive and caudal portion being negative.

PMID- 18074787
TI  - [Pharmacological sympatectomy changes heart's inotropic reaction on serotonin in
      postnatal ontogenesis of rats].
AB  - In the present study, the influence of 0.1 microM, 1.0 microM, 10.0 microM
      serotonin (5-HT) on inotropic function (contraction force, time to peak force,
      time to relaxation) of desympathetized rats by guanethidine in postnatal
      ontogenesis was investigated. 5-HT has a positive inotropic effect on atria (178
      %) and ventricles (122%) in 21-day old rats. In 21-day old desympathetized rats,
      serotonin influence on the atrium was depressed by 49 %, while ventricle
      contraction did not change. Atria contraction force in 100-day old rats increased
      by 38 %, while ventricle contraction force was decreased by 5-HT. In the 100-day
      old desympathetized rats, a significant elevation ofinotropic effect of 5-HT in
      atria by 91% and ventricles by 51% was revealed. It was shown that injection of
      guanethidine during three weeks since birth changes reaction on 5-HT in postnatal
      ontogenesis ofrats. In 21-day old desympathetized rats, 5-HT had a negative
      inotropic effect in the early period after pharmacological sympatectomy, while in
      the period of compensation the elevation of the positive inotropic effect of 5-HT
      occurred. Positive inotropic effect of atria in 100-day old desympathetized rats
      was twice as high as in control group. Our data suggest that there exists an
      interaction between adrenergic and 5-HT regulation in postnatal ontogenesis of
      rats.

PMID- 18074788
TI  - [Reloading of rat soleus after hindlimb unloading and serum insulin-like growth
      factor 1].
AB  - The aim of this study was to elucidate the effects of 14- day hindlimb suspension
      (HS) and subsqquent reloading (3 or 7 days) on the m. soleus mass, muscle fiber
      cross-sectional area (CSA), soleus fiber properties and serum IGF-1 in rats. Rats
      were hindlimb suspended for 14 days or kept as controls (C, n = 7). Soleus
      muscles were isolated after HS (HS, n = 7) or after reambulation for either three
      (R3, n = 5) or seven days (R7, n = 6). Frozen serial sections of m. soleus were
      stained by primary monoclonal antibodies against MHCI. For measurement of
      concentration IGF-1 in the blood serum, test-system for IFA DSL-10-2800 Non
      Extraction IGF-1 ELISA was used. Muscle mass was significantly reduced in HS (-35
      %) but subsequently increased with reloading in R3 (-10 % to C) and was recovered
      to control values in R7 (+5 % to C). Fiber CSA was significantly reduced (-43 %)
      in HS and was greater in R7 than in HS and slightly greater than in R3. 14 days
      of HS resulted in a mean maximal tension reduced by 35 %. After 7 days of
      subsequent reloading the mean maximal specific tension was still low (-33 % to C)
      and didn't differ from HS level. The level in blood IGF-1 has obviously decreased
      during 14-day unloading by 48 %, remained at the same level in R3, and increased
      10 fold in R7.

PMID- 18074789
TI  - [Presynaptic 5-HT1A receptors in immunomodulation].
AB  - It is shown that a selective agonist of 5-HT1A receptors 8-OH-DPAT in a low dose
      (0.1 mg/kg), which is known to affect mainly the presynaptic 5-HT1A receptors
      increased the immune response at the peak of reactions (the forth or fifth day
      after immunization with sheep red blood cells - SRBC) in CBA mice and Wistar
      rats. Treatment of the animals with the drug 15 min prior to antigen injection
      raised the number of plaque-forming cells (lgM-PFC) and rosette-forming cells
      (RFC) in the spleen. The preliminary blockade of 5-HT1A receptor with a selective
      antagonist of 5-HT1A receptors WAY-100635 (0.1 mg/kg) prevented the
      immunostimulating effect of 5-HT 1A receptors agonist 8-OH-DPAT, whereas WAY
      100635 administration alone in the same dose didn't change the immune response.
      Activation of 5-HT1A receptors under conditions of electrical lesion of 5-HTergic
      neurons of the nucleus raphe was unable to enhance the immune reactions, as it
      did in sham-operated rats. The data obtained indicate that the somatodendric 5
      HT1A autoreceptors are involved in immunomodulation.

PMID- 18074791
TI  - [Development of hypothermia in rats at increase of [Ca2+] in the blood].
AB  - In rats, data on influence of i. v. administration of calcium chloride on the
      level of [Ca2+] in the blood and on process of oppression ofthermoregulatory and
      respiratory functions in rats in hypothermia. 0.18 or 0.135 mmol Ca2+ on the 3rd
      minute from beginning of the administration increased [Ca2+] in the blood from
      1.01 +/- 0.03 to 2.56 +/- 0.08 mM (or 2.27 +/- 0.06 mM). Then [Ca2+] was reduced
      gradually, in 20 minutes from administration, solution of CaCh [Ca2+] exceeded
      the initial level by 20-30 %. The increase of concentration of ionized calcium in
      the rat blood strengthened the cold oppression of breathing and cold shivering as
      compared with the control (administration of physiological solution). Arrest of
      breathing in rats after administration of CaCl2 solution occurred at higher
      rectal temperatures (21 +/- 0.03 degrees C) as compared with control experiments
      (18 +/- 0.4 degrees C), p < 0.05. It is suggested that increase of [Ca2+] in the
      blood strengthens effects of cold in the form of oppression of thermoregulatory
      and respiratory functions.

PMID- 18074790
TI  - [Alteration of trachea and bronchi smooth muscles constriction under long
      inhalation of dioxide nitrogen by rats].
AB  - On insulated preparation of trachea and bronchi, change of the smooth muscles
      constriction was studied in rats inhaling dioxide nitrogen during 15, 30 and 60
      days. The inhalation enhanced 1.5-fold and bronchi 2.5-fold responses of tracheal
      smooth muscles to stimulation of preganglionic nerve. The delay of the response
      in both events increased 1.3-fold. Long repeated stimulation caused a further
      increase of the constriction of tracheas and bronchi (1.32-fold). Blocking
      receptor with Novocain (1.0 mcg/ml) reduced the amplitude of the constriction and
      enhanced the response delay. After 30 days of inhalation, repeated nerve
      stimulations enhanced the amplitude of the constriction up to 120%, but after 60
      days it reduced the amplitude of the constriction to 71 and 77% in preparations
      of tracheas and bronchi, respectively. In our opinion, long inhalation of dioxide
      nitrogen broke functioning of local lung nervous system controlling activity of
      the smooth muscles. The research results indicate important role of neuron
      functional module in pathology of the respiratory ways caused inhalation of
      dioxide nitrogen.

PMID- 18074792
TI  - [Restoration of contractions of isolated heart arrested in result of progressing
      hypothermia with electrical stimuli and no warming up of the heart].
AB  - In the rat isolated heart, the effect of cooling with the velocity 0.2 degrees
      C/min and its stimulation with rectangle electrical pulses (19 Hz, 100 ms, 1-5 V
      amplitude) on the heart mechanical activity in mcWatt/g was studied as the
      product of heart shortening on contraction strength and heart rate. The heart
      shortening was measured by the Langendorf method. Heart contractions activated
      the recording system with the aid of a hook at the apex. The Ringer-Lokk solution
      served as perfusate pumped with peristaltic pump. After cold arrest of automatic
      contractions (on the average at 9.3 +/- 0.7 degrees C), the heart continued to
      respond with contractions to electrical pulses of 5 V amplitude, the power of the
      heart contractions at 10 degrees C being on the average 35 % of the initial power
      at 20 degrees C. Excitability and contractility of the heart terminate at 5.3 +/-
      0.4 degrees C.

PMID- 18074793
TI  - [Motor responses of the colon to stimulation of the sacral parasympathetic
      nucleus neurons].
AB  - In acute experiments on urethane-anaesthetized cats, motor responses of different
      parts of the colon (the proximal and descending parts as well the rectum) to
      microstimulation of neurons of the sacral parasympathetic nucleus (SPN) were
      investigated. The stimulation was carried out by rectangle pulses of current with
      intensity 100-1000 microA, pulse width 0.5 ms and frequency 10 Hz. It was shown
      that the microstimulation of the SPN neurons located within SI-SIII segments of
      spinal cord induced mainly the excitatory motor responses of all regions of the
      colon. However the most pronounced responses were obtained when the neurons of
      SII segments were stimulated. On the whole, the responses of rectum to
      stimulation were greater than responses of the proximal part of the colon. Our
      results suggest that the SPN neurons located within SII segments play the most
      important role in reflex control of colon motility.

PMID- 18074794
TI  - [Dynamics of food intake and blood level of hormones regulating appetite in
      pregnant and lactating mice].
AB  - Leptin, insulin, corticosterone regulate food intake. Hyperphagia and hormonal
      rearrangement are typical for pregnancy and lactation. The aim of the study is to
      correlate food intake with blood levels of these hormones in pregnant and
      lactating mice. Food intake, body weight, blood glucose, insulin, leptin and
      corticosterone levels were measured in virgin C57B1/6J micc and on the day 7,
      13,17 of pregnancy, and day 1, 7, 14, 30 postpartum. Insulin sensitivity was
      measured at the day 7, 17 of pregnancy. Food intake and body weight increased
      towards the second postpartum week and then decreased. Insulin sensitivity
      decreased towards the end of the pregnancy. Mothers differed from virgin females
      in hormones and glucose levels only during pregnancy. Leptin level was decreased
      at the day 7 of gestation, insulin level - during whole gestation. Glucose fell,
      and leptin and corticosterone increased from the day 7 to 17. Probably, these
      hormones affect food intake only in pregnant females and do not influence
      appetite during lactation.

PMID- 18074795
TI  - [Success in water competition test is influenced with anxiety levels, but not
      with resident status of the rat].

PMID- 18074796
TI  - [Isolated neuron-based biosensor for release of neuroactive substances].

PMID- 18074797
TI  - [Effect of tamoxifen on anxiety in ovariectomized and intact female rats].
AB  - The effect of tamoxifen (estrogen receptor modulator) administered in a daily
      dose of 10 mg/kg (i.p.) over 14 days on the behavioral state of female rats has
      been studied in various phase of the sexual cycle and in the state of estrogen
      deficiency. In the elevated-plus-maze and open-field tests, the administration of
      tamoxifen to intact rats was accompanied by anxiolytic and/or anxiogenic effects,
      depending on the phase of the sexual cycle. The ovaryectomy led to a sharp
      increase in the anxiety. The chronic administration of tamoxifen in
      ovaryectomized female rats produced a stronger anxiolytic effect in comparison to
      17beta3-estradiol. The results show that tamoxifen produces a modulating action
      on the state of anxiety, which depends on the estrogen level in the blood.

PMID- 18074798
TI  - [Radioreceptor study of [3H]-olanzapine specific binding in the rat frontal
      cortex and striatum].
AB  - The direct radioreceptor assay was used to elucidate the interactions of
      clinically employed atypical antipsychotic drug olanzapine with the specific
      binding sites in rat brain membranes. Tritium-labeled olanzapine was obtained by
      isotope exchange method. HPLC and mass spectrometry assays confirmed the identity
      of [3H]-olanzapine to the initial compound. The specific [3H]-olanzapine binding
      sites of the two types were identified in frontal cortex by means of the method
      of Scatchard's plots. High affinity sites showed steady-state dissociation
      binding constant (KD) of 1.7 nM, which is indicative of olanzapine affinity to 5
      HT-2a and histamine receptors. However, according to available literature data,
      the density of these receptors is several times smaller than that determined in
      our study (maximum number of binding sites corresponded to B(max) = 1.4 pmol/mg
      protein), thus allowing an assumption about the existence of yet unknown binding
      sites of the antipsychotic drug under consideration. Moderate affinity binding
      sites of olanzapine in frontal cortex (KD= 68.5 nM, B(max) = 10.8 pmol/mg
      protein) apparently correspond to dopamine, muscarinic, and alpha-1
      adrenoceptors. [3H]olanzapine binding sites of the two types were also determined
      in striatum. The moderate-affinity sites of the receptor interaction had KD =
      18.0 nM and B(max) = 13.0 pmol/mg protein. These values in fact correspond to D2
      receptors, whose density prevails in this cortical region. The low-affinity
      binding sites of olanzapine in striatum had KD = 117.0 nM and B(max) = 32.5
      pmol/mg protein.

PMID- 18074800
TI  - [Chronic administration of serotonin transporter inhibitor (fluoxetine) decreases
      monocrotaline-induced pulmonary hypertension in rats].
AB  - The effect of a chronic fluoxetine treatment on the development of monocrotaline
      induced pulmonary hypertension has been studied in rats. It was found that
      fluoxetine decreased right ventricular hypertrophy and reduces pulmonary vessels
      thickness. These results suggest that chronic fluoxetine treatment can lead to a
      decrease in the manifestation of pulmonary hypertension symptoms.

PMID- 18074799
TI  - [Comparison of neuroprotective properties of nootropes, calcium channel blockers,
      and panangin].
AB  - Neuroprotective properties of a series of drugs including nootropes, calcium
      channel antagonists, and panangin have been studied on a model of craniocerebral
      trauma. It is established that beglimin and nooglutil exhibit a moderate
      antiischemic, antihypoxic, and antiamnesic action in posttraumatic period;
      panangin possesses antiischemic, anticonvulsant, and antiamnesic properties;
      while nimodipin exhibit only antiamnesic action. It is concluded that beglimin,
      nooglutil and panangin are of importance in the pharmacological treatment of
      secondary traumatic brain injury.

PMID- 18074801
TI  - [Experimental evaluation of the antiulcer activity of calcium pectate].
AB  - Both chronic (prophylactic) and single administration of standardized calcium
      pectate considerably increased the resistance of rat stomach mucous membrane with
      respect to ulcerogenic factors of various etiology, including immobilized stress,
      indomethacin, ethanol, prednizolone, and histamine, according to H. Shay's model.
      The gastroprotective effect of this polysaccharide was comparable with or
      exceeded the action of famotidine, sea buckthorn oil, and maalox.

PMID- 18074802
TI  - [The regulatory effect of mexidol on the hemoglobin level under acute stress
      conditions].
AB  - Experiments on a group of 39 Wistar albino male rats showed that, 2 and 5 days
      after a model acute stress procedure, the total amount of erythrocytes is
      increased. This process is accompanied by a hypochromia of red cells and by a
      decrease in the concentration of serum iron. Single administration of mexidol
      (100 mg/kg) before stress induction prevents changes in the amount of blood
      erythrocytes, as well as in their saturation with hemoglobin. Mexidol also
      prevents a decrease in the level of serum iron. The drug does not influence the
      hematological parameters and iron concentration in blood serum of intact animals
      2 and 5 days after injection.

PMID- 18074803
TI  - [Influence of taurine-zinc sulfate composition on the free amino acid level in
      blood plasma and the liver].
AB  - The intraperitoneal injection of taurine--zinc sulfate composition (400 mg/kg
      body weight) led to a considerable increase in the plasma taurine levels,
      activated the hepatic uptake of free amino acids, and modulated the metabolism of
      sulfur-containing amino acids.

PMID- 18074804
TI  - [Suppression of immune response associated with functions of B-cells, Th1- and
      Th2-lymphocytes and interleukins produced by these cells, and pharmacological
      correction of these disturbances upon acute intoxication with methanol].
AB  - Experiments on Wistar rats showed that acute poisoning with methanol (0.75 LD50)
      leads to the suppression of cellular and humoral immune responses and decreases
      the blood concentration of interleukins (IL-2, IL-4) with an increase in the IL
      2/IL-4 ratio. These facts indicate that a decrease in Th2 lymphocyte activity is
      more pronounced in comparison to that of Th1 cells. The immunomodulators
      mielopide and polyoxidon administered in a daily dose of 10 mg/kg for 4 days upon
      acute poisoning with methanol virtually completely restore the cellular and
      humoral immune responses, the activity of natural killers, and the synthesis of
      interleukins.

PMID- 18074805
TI  - [Antiviral action of some antioxidants/antihypoxants and their combinations with
      remantadine against human influenza A(H3N2) virus studied in in vitro models].
AB  - The possible antiviral activity of preparations with antioxidant and/or
      antihypoxant properties was studied on two in vitro models of influenza
      infection: (i) in cultures of chorio-allantoic membranes of chicken embryos and
      (ii) in MDCK cells. Preparations under study were hypoxene, reduced glutathione,
      dihydroquercetin, trolox, coenzyme Q10, and the enzymatic preparation of
      superoxide-dismutase (recsod). Preparations possessing combined
      antioxidant/antihypoxic and detoxicating properties (reduced glutathione and
      hypoxene) produced a significant antiviral effect and enhanced the antiviral
      effect of rimantadine. The antiviral effect of these preparations was manifested
      by a decrease in the production of viral particles and, to a more pronounced
      degree, by the inhibition of cytopathogenic action of virus on cultured cells,
      which was revealed in the tests for the activity of respiratory enzymes. In
      contrast to the compounds containing thio or sulfo groups, the antioxidants of
      "direct action" (free radical scavengers) - coenzyme Q 10, trolox, quercetin and
      the enzymatic preparation recsod did not show any pronounced protective effect
      and in some cases even enhanced the production of viral particles and decreased
      the antiviral action of rimantadine.

PMID- 18074806
TI  - [Effect of taurine on the pool of central neuroactive compounds during ethanol
      withdrawal syndrome].
AB  - Influence of taurine on the pool of central neuroactive compounds during alcohol
      withdrawal syndrome has been investigated. Alcohol withdrawal syndrome was
      accompanied by a pronounced dysbalance in the formation of the pool of
      neuroactive compounds. The most remarkable changes were found in the levels of
      markers related to the central serotoninergic system, as well as dopaminergic
      system. Taurine administration in a dose of 650 mg/kg (i.g.) one hour before
      decapitation during ethanol withdrawal syndrome alleviates disturbances in the
      functioning of serotoninergic and (to a lesser extent) dopaminergic systems and
      improves the ratio of inhibitory and excitatory mediator amino acids.

PMID- 18074807
TI  - [Using carnosine and natural antioxidants for the prophylaxis of acute post
      loading oxidative stress].
AB  - The effects of a submaximum single physical load with a mixed aerobic-anaerobic
      character (combined rowing test) on the intensity of lipid peroxidation (LPO)
      processes, antioxidant state of the organism, and rheological properties of blood
      have been studied in a group of athletes. The administration of natural
      antioxidants significantly decreased the LPO stress induced by the physical load,
      reduced the suppression of the antioxidant system of the organism, and normalized
      the LPO-disturbed hemorheological parameters. Antioxidants such as carnosine,
      cytamine, and apilac can be used as non-doping means for the accelerated recovery
      and increase in the physical work capacity in athletes.

PMID- 18074808
TI  - [Antihypoxant effect of zinc(II) bis(N-acetyl-L-cysteinato)sulfate octahydrate in
      acute normobaric hypoxia].
AB  - Using two models of the acute normobaric hypercapnic hypoxia (ANHH) and acute
      normobaric hypoxia without hypercapnia (ANWH), some parameters of the impulse
      activity of somatosensory cortex neurons were studied in experiments on cats. A
      new antihypoxant drug--aminothiol complex substance composed of zinc(II) and N
      acetyl-L-cysteine (piQ-1104, 50 mg/kg)--was used for the brain protection. The
      substance studied showed a high antihypoxant activity in the brain neurons during
      all stages of both ANHH and AHWH. The average active survival time during hypoxic
      state was increased 2-2.5 times in comparison to the control group. The neuron
      activity dynamics under ANHH and AHWH conditions and after piQ-1104 injection was
      observed.

PMID- 18074809
TI  - [Chronobiological similarity of the specific activity of anxiolytic and
      antidepressant drugs].
AB  - An analysis of the recent achievements in chronobiology shows that the specific
      activity of anxiolytic and antidepressant drugs can be related to identical
      reorganization of the biological rhythms and the function of brain structures,
      which control rhythmical processes.

PMID- 18074810
TI  - [Cardioprotective and antiarrhythmic properties of Rhodiolae roseae
      preparations].
AB  - It is established that the chronic administration of Rhodiola rosea extract (RRE)
      in a single daily dose of 1 ml/kg (p.o.) during 8 days increased the resistance
      of myocardium with respect to the cardiotoxic action of isoproterenol and the
      arrhythmogenic action of epinephrine in rats. Pretreatment with RRE prevented the
      stressor cardiac damages, as measured by 99mTc-pyrophosphate accumulation in the
      heart. The cardioprotective action of RRE was maximum after 5-day administration.
      The antiarrhythmic effect of the adaptogen was maximum after 8-day
      administration. It was found that p-tyrosol also exhibited antiarrhythmic and
      cardioprotective properties. Pretreatment with RRE decreased the infarction
      size/risk area ratio during the coronary artery occlusion and reperfusion in
      vivo. The chronic administration of RRE increased th e tolerance of the isolated
      perfused rat heart to the pathogenic action of global ischemia and reperfusion.
      Pretreatment with RRE not only prevented the occurrence of arrhythmias, but also
      abolished cardiac electrical instability in rats with postinfarction cardiac
      sclerosis. It has been found that the chronic administration of RRE (1 ml/kg,
      p.o., over 8 days) increased the level beta-endorphin in rat blood plasma and the
      content of leu-enkephalin in myocardial tissue. Naloxone (2 mg/kg) abolished
      cardioprotective and antiarrhythmic effect of the adaptogen. It was suggested
      that both RRE effects depend on the occupancy of opioid receptors by endogenous
      opioid peptides. It has been found that the sympathetic nervous system is
      involved in the development of antiarrhythmic effect of RRE, while HSP-70 is not
      involved in the cardioprotective and antiarrhythmic effect of adaptogen. It is
      concluded that the mechanism of cardioprotective and antiarrhythmic action of RRE
      needs further investigation.

PMID- 18074811
TI  - [A. A. Maksimov: on the 100th anniversary of the unitarian theory of
      hematopoiesis].
AB  - The life and scientific activity of the prominent Russian morphologist A. A.
      Maksimov are described. The scientist created the unitarian theory of
      hematopoiesis and wrote a textbook on history which appeared in 12 editions and
      acquired a worldwide popularity. The paper contains some unique materials that
      first appeared in Russia.

PMID- 18074812
TI  - [Current views of the histogenesis and pathogenesis of Hodgkin lymphoma].
AB  - The diagnosis of Hodgkin lymphoma is based on the identification of Beresovsky
      Reed-Sternberg (B-R-S) cells which are surrounded by inflammatory cells. The
      tumor cells are of B-cell origin and their mutations are sometimes observed. T
      cell immunophenotype is recorded in 5% of the observations. Epstein-Barr virus is
      found in one third of the patients.

PMID- 18074813
TI  - [Current approaches to diagnosing and treating primary cutaneous lymphomas on the
      basis of a new WHO-EORTC classification, cutaneous T-cell lymphomas].
AB  - This two-part review addresses the current diagnostic approaches towards primary
      cutaneous lymphomas. In this part, main T and NK-cell lymphomas are described
      with reference to clinical presentation, histological and immunohistochemical
      features, and genetic alterations based on the new WHO-EORTC classification of
      cutaneous lymphomas.

PMID- 18074814
TI  - [Parenchymatous-stromal factors in hemoblastoses].
AB  - The data available in the literature data on the role of neoangiogenesis and
      extracellular matrix factors in the pathogenesis of acute and chronic leukemias
      and lymphoproliferative diseases are presented. Hematopoiesis and endothelial
      cells have a common pluripotential progenitor. Angiogenic and fibroblast growth
      factors are involved chronic leukemia. The phenotype of lymphoid cells determines
      the type of the cellular and extracellular factors.

PMID- 18074815
TI  - [Immunomorphological characteristics and criteria for predicting gastrointestinal
      stromal tumors].
AB  - The study of 36 cases of gastrointestinal stromal tumors (GIST) (n = 26 of the
      stomach and n = 10 of the duodenum, small bowel, and rectum) indicated that among
      the clinical symptoms, there were prevalent abdominal pains and gastrointestinal
      bleeding. Local invasion and metastases were detected in 11 patients. According
      to the risk of aggressiveness, 1 tumor presented a very low risk; 5, a low risk;
      14, a moderate risk; and 16 a high risk. All GISTs with mucosal infiltration were
      in high and moderate risk groups. The expression of p27 did not depend on that of
      other markers, the sizes of a tumor, its histological type, and affinity to this
      or that risk group. There was a statistically significant difference in the
      expression of Ki-67 in the groups of low (1.7%) and high (10.3%) risks.

PMID- 18074816
TI  - [PRP(CJD) reproduction in the cerebral vascular plexus epitheliocytes in a new
      type of Creutzfeldt-Jakob disease].
AB  - The study of brain histological specimens from patients with Creutzfeldt-Jakob
      disease (CJD) revealed the active reproduction and accumulation of pathological
      prions in the epitheliocytes of cerebral vascular brain plexuses in a new variant
      of CJD. There was PrPCD accumulation on the cerebral ventricular ependymal cells
      and in the subpial superficial cortex parts of the cerebellum and brain to give
      rise to diffuse clusters, immature and kuru-plaques. Morphological changes in the
      blood-cerebrospinal fluid and cerebrospinal fluid-brain barriers are described
      and the possible pathways of intracerebral distribution of prions with
      cerebrospinal fluid considered.

PMID- 18074817
TI  - [Endometrial decidualization as a factor that regulates cytothrophoblastic
      invasion during the first trimester of pregnancy].
AB  - Endometrial stromal cell decidualization is a multistage process that starts with
      the late secretory phase of a menstrual cycle and then continues in the first
      months of pregnancy. Under the influence of the hormone progesterone, precursor
      cells undergo a unique structural and functional transformation from the
      adventitional cells of spiral arteries containing a marker of smooth muscles
      (desmin) through pre-decidual cells to the decidual intermediate cells expressing
      a marker of the extraembryonic mesoderm (vimentin), and IGFBR-1 and then to the
      typical epithelioid decidual cells.

PMID- 18074818
TI  - [Small-cell variant of renal oncocytoma].
AB  - Renal oncocytoma is a distinct benign tumor accounting for approximately 3-5% of
      all renal tumors. This neoplasm is easily recognizable in its classic form: there
      are polygonal cells with abundant granular eosinophilic cytoplasm filled with
      mitochondria. The tumor cells are arranged in nests and tubular pattern. Here, 1
      case of renal oncocytoma with a domination of small cells is reported (the so
      called "oncoblasts") arising in elderly woman. These small cells have scant
      cytoplasm, dense hyperchromatic nuclei, and a high nuclear/cytoplasmic ratio. The
      term "small-cell variant of renal oncocytoma" was proposed for these cases. The
      unusual extensive small-cell component of the tumor may represent a potential
      diagnostic pitfall for primary or metastatic malignant small cell tumors.

PMID- 18074819
TI  - [Immunohistochemical study in the diagnosis of tuberculosis].
AB  - The comparative analysis of the immunohistochemical method and Ziehl-Neelsen
      staining was used to search for a new highly sensitivity procedure for diagnosing
      tuberculosis. With both methods, mycobacteria tuberculosis were detected in 10
      cases of fibrocavernous pulmonary tuberculosis, 1 case of general tuberculosis,
      and 10 cases of disseminated lung lesion (sarcoidosis?). The improved
      immunohistochemical option using Mycobacterium tuberculosis antibodies (clone
      1.1/3/1) have shown AEC and appeared to be the most sensitive than the Ziehl
      Neelsen staining and may be therefore recommended for the diagnosis of
      tuberculosis.

PMID- 18074820
TI  - [Outstanding Russian pathologist (on the 120th anniversary of I. V. Davidovsky's
      birth)].

PMID- 18074821
TI  - [Cavernous hemangiomas of the skin of the face and neck and the oral soft
      tissues].
AB  - The structure, clinical manifestations, behavior of cavernous hemangomas of the
      skin of the face and neck, and the oral soft tissues were studied, by using
      biopsy specimens from 229 patients. Three types of cavernous hemagiomas of these
      areas were identified. Their preferred treatments were defined and
      pathogenetically warranted.

PMID- 18074822
TI  - [Chondromas (enchondroma, periosteal chondroma, enchondromatosis)].
AB  - Chondromas combine a group of benign cartilaginous tissue tumors with common
      histological manifestations. The tumors (enchondroma, periosteal chondroma, and
      enchondromatosis) differ in sites and clinical manifestations. Chondromas are
      generally hypocellular, avascular tumors with an abundance of hyaline cartilage
      matrix and chondrocytes located diffusely, in clones or lobules. Small bone
      chondromas, Ollier's disease, and Mafucci's syndrome are characterized by the
      tumor tissue containing a large number of cells and by greater cytological
      atypia. Enchondroma is successfully treated by surgical methods.

PMID- 18074823
TI  - [Meningiomas: anatomical pathology and molecular biology].
AB  - In the past 5-10 years, there has been a considerable progress the understanding
      of the biology of meningioma. The most important advances have been made by
      comprehensive studies of the pathogenesis of meningioma in molecular genetics.
      Several target genes could be identified for mutation or inactivation. Additional
      chromosomal regions that are usually subject to deletion or amplification and
      point to the presence of tumor suppressor genes or proto-oncogenes were found.
      The revised and updated 2000 WHO Classification is a major innovation in the
      histopathology of meningiomas. The new classification system more precisely and
      objectively determines the grade of meningioma, which allows one to more
      logically make a prognosis of the recurrence and aggressive behavior of the
      tumor. The present overview places particular emphasis on recent advances in its
      molecular biology. It summarizes the most important aspects of the classification
      of meningiomas, which makes it possible to include the results of biological
      observations into the respective context, and also considers the mechanisms of
      angiogenesis and edema development and the role of hormonal receptors in
      meningiomas.

PMID- 18074824
TI  - [Clinical and morphological characteristics of gastrointestinal stromal tumors].
AB  - GIST are stromal tumors and the gastrointestinal tract (GIT) and some other
      organs of spindle-cell or epithelioid-cell structure expressing CD117 (C-kit,
      KIT), as well as those at different rates and in different combinations, CD34,
      smooth muscle and/or neurogenic differentiation antigens. It should be taken into
      account that CD117 are also expressed by melanomas, vascular, and some other
      tumors. The c-kit gene mutations leading to the expression and autoactivation of
      the tyrosine kinase receptor KIT underlie the oncogenesis of GIST, which results
      in enhanced proliferative activity and inhibited apoptosis. This is supported by
      successful chemotherapy for GIST with a KIT receptor inhibitor. The histogenesis
      of GIST is associated with GIT somatic stem, the Cajal cell precursors. Many
      GISTs behave like sarcomas and they are characterized by an infiltrating growth,
      hematogenic (mainly into the liver) and implantational (along the peritoneum)
      cancer spread. There are opinions that all such neoplasms are potentially
      malignany and small-sized GISTs are benign and have the minimum mitotic activity.

PMID- 18074825
TI  - [Perinatal stroke--clinical validity of the ET 6-6].
AB  - BACKGROUND: The present study evaluates the role of the clinical use of the ET 6
      6 as a general developmental test in assessing impairments following perinatal
      stroke. METHODS: 32 children aged 36 up to 72 months who had suffered a perinatal
      stroke were matched with a corresponding control group and assessed by means of
      the ET 6-6. A specification of developmental difficulties was evaluated according
      to the localisation of the stroke. Differences in performance were analyzed using
      nonparametric tests. RESULTS: The study group showed a significantly lower level
      of performance in almost every dimension of development. Children with left
      hemispheric stroke displayed greater developmental impairment than did children
      with right-hemispheric or basal ganglia stroke. CONCLUSIONS: These data suggest
      the applicability of the ET 6-6 in assessing developmental risks caused by
      perinatal stroke.

PMID- 18074826
TI  - [Early identification of language delay among two-year-olds--a comparison of
      methods].
AB  - OBJECTIVE: In recent years, several language tests and parent questionnaires
      targeting the early identification of language delay have been developed. The
      present study compares the results from two such language tests administered to
      two-year-old children and those from a parent report measure. METHOD: Thirty-one
      normally developing or late-talking toddlers (aged 24 to 28 months) were included
      in the study. Their language skills were assessed by means of a parent report
      (ELFRA-2, a German version of the MacArthur Communicative Development Inventories
      -CDI, Toddler Form) and two language tests (SETK-2, RDLS III). RESULTS: The
      concordance regarding the level of language skills was high for all three
      measures. The correlations between subtest measures that assess similar language
      dimensions varied between rSp = 0.7 and 0.9. Most children who were classified as
      late talkers based on the parent report measure were also classified as having a
      language delay on the basis of both language tests. However, the language delay
      on the part of the late-talking children usually was not recognized during the
      routine pediatric examination at the age of 24 months. CONCLUSIONS: Parent
      reports and language tests identify late talkers almost equally well. Hence, the
      parent questionnaire ELFRA-2 is recommended as the primary instrument for the
      early identification of late talkers at age two. If the results on the parent
      report are below normal, further assessment of the child's language abilities by
      means of the SETK-2 is advisable. In contrast to language assessment on the basis
      of the parent report, assessment based on the SETK-2 provides information on
      language comprehension and thus enables a more sophisticated assessment of the
      child's language skills. The SETK-2 consists mainly of pictures, however. For
      those children who show little interest in the pictures in a clinical setting,
      use of the RDLS III should be considered.

PMID- 18074827
TI  - [Perception of emotional facial expressions in female adolescents with borderline
      personality disorder].
AB  - OBJECTIVES: Investigation of the perception of emotional and neutral facial
      expressions in female adolescents with borderline personality disorder (BPD).
      METHODS: Emotional and neutral facial expressions from the set of Ekman and
      Friesen were presented to 30 adolescent patients with a diagnosis of BPD, to 29
      adolescent patients with other psychiatric diagnoses, and to a control group of
      30 healthy subjects. All participants in the study were female. The subjects were
      asked to name the displayed emotion and to estimate the perceived intensity,
      negativity and pleasantness by means of a self-developed questionnaire on the
      perception of emotions in facial expressions. RESULTS: Female adolescents with
      BPD demonstrated no deficits in naming the displayed emotions. Nor did they
      differ from the clinical and healthy control groups regarding the subjective
      ratings of the negative and neutral facial expressions. However, female
      adolescents with BPD rated the pleasantness and intensity of positive facial
      expressions lower, and the negativity of positive facial expressions higher than
      did either the clinical or the healthy control group. CONCLUSIONS: The findings
      suggest the need for further research on the processing of positive stimuli and
      its role in the regulation of emotion in adolescents with borderline personality
      disorder. Due to the dysfunctional interpretation of positive emotional stimuli,
      therapeutic efforts should also rely on the possible biases in emotional
      information processing.

PMID- 18074828
TI  - [German version of the math anxiety questionnaire (FRA) for 6- to 9-year-old
      children].
AB  - OBJECTIVES: Is the FRA a reliable and valid instrument? Are there any gender
      differences concerning math anxiety? Are there any developmental changes in this
      regard in the course of the early grades? METHODS: Together with the dyscalculia
      test TEDI-MATH, the FRA was presented to a total of 450 children from the first
      to the third grade of primary school (at least 40 girls and 40 boys per
      semester). RESULTS: The total scale has an internal consistency (Cronbach's
      alpha) between 0.83 and 0.91. Correlations between arithmetic skills and the FRA
      scales were mostly significant. The significantly higher negative scores for
      girls were taken into account by providing standard scores corrected for gender.
      No systematic developmental changes could be observed. CONCLUSIONS: The FRA is
      the first German math anxiety questionnaire for primary school children. High
      reliability, standard scores corrected for gender, and economic handling make it
      an instrument well suited for use in clinical settings (e.g., dyscalculia
      diagnostics and intervention).

PMID- 18074829
TI  - [22q11.2 deletion and schizophrenia in childhood and adolescence].
AB  - 22q11.2 deletion is the most common microdeletion in humans and one of the most
      important risk factors for schizophrenia. Nevertheless, case reports of children
      or adolescents with 22q11.2 deletion and schizophrenia are very rare. After a
      review of the current knowledge about physical, developmental, behavioural and
      psychiatric problems in 22q11.2 deletion, the case of a 12;10-year-old boy with
      schizophrenia and the microdeletion is reported. About three years after the
      first symptoms, and only after medication with several neuroleptics, the patient
      reached his pre-morbid functioning level under treatment with risperidone. Under
      medication with clozapine he had experienced a single event of seizures which
      were due to hypocalcemia. This case report illustrates the importance of serum
      calcium controls at regular intervals for patients with 22q11.2 deletion and
      schizophrenia who are on neuroleptic medication. Ideally, children and
      adolescents with the deletion and co-morbid psychiatric problems should be
      treated in child and adolescent psychiatry units specialized in problems
      associated with the deletion. A good cooperation with other medical services is
      absolutely necessary.

PMID- 18074830
TI  - [Minimal standards of imprisonment].

PMID- 18074831
TI  - [Study on cryopreservation of Pueraria lobata germplasm by vitrification].
AB  - The experiment of the cryopreservation technique on Pueraria lobata showed that:
      At first, the aseptic explants were treated at 4 degrees C for 5 days. Then the
      stems with buds were cut and precultured at 4 degrees C for 1 day in 5% DMSO + 5%
      sucrose media. They were dehydrated with 60% and 100% PVS2 (30% glycerol + 15%
      glycol + 15% dimethyl sulfoxide + 0.4 mol/L sucrose) at 0 degrees C for 30
      minutes respectively. At last the stems were immersed immediately into liquid
      nitrogen directly and conserved for 24 hours. After rapidly thawing in a water
      bath at 40 degrees C for 90 seconds, the stems were washed two times with MS
      media supplemented with 1.2 mol/L sucrose and 10 minutes each time, then
      transferred on the MS media supplemented with BA 2 mg/L and NAA 1 mg/l, in dark
      for 7 days and then in light. The survival rate was up to 57-58% . The
      regenerated plant of Pueraria lobata were the same as the normal in morphology.

PMID- 18074832
TI  - [Selection of the microorganism for dioscin hydrolyze].
AB  - OBJECTIVE: To select the microorganism which can hydrolyze dioscin to diosgenin.
      METHODS: The microorganism were selected from the surface of rhizome, rhizosphere
      soil, the inside of the leaves and rhizome of Dioscorea zingiberensis C. H.
      Wright. Diosgenin was identified by thin-layer chromatography and HPLC. RESULTS:
      The microorganism which could hydrolyze dioscin from the experiment were
      identified as Aspergillus sp and Alternaria sp. Characteristics of enzymes
      production and fermentation technology of Aspergillus No. 1 were also studied
      primarily. CONCLUSION: The Aspergillus strain No. 1 can secret enzyme to
      hydrolyze dioscin into diosgenin effectively.

PMID- 18074833
TI  - [Study of anticoagulant activity of ethanol extracts from leech in vitro].
AB  - OBJECTIVE: To study the anticoagulant activity of different portions of leech
      ethanol extracts (LEEs). METHODS: Anticoagulant activity was determined by
      measuring prothrombin time(PT), thrombin time (TT), activated partial
      throboplstin time (APTT) and fibrinogen coagulation time (FCT). RESULTS: PT, TT,
      APTT and FCT were remarkably prolonged by ethyl acetate portion of LEEs. Portions
      of petroleum ethrer, n-butanol and water extracted from LEEs was much weaker on
      anticoagulant activity. CONCLUSION: The anticoagulant effect of ethyl acetate
      extract portion of LEEs is the strongest among the four portions, and this
      results may be from its inhibitory effect on thrombin-catalyzed fibrinogen
      hydrolysis.

PMID- 18074834
TI  - [Comparison of flavonoids in medicinal plants Melastoma].
AB  - The flavonoids in Melastoma dodecandrum Lour., M. sanguineum Sims, M. normale D.
      Don, M. affine D. Don and M. candidum D. Don were compared by Thin Layer
      Chromatography (TLC). Rutin was detected in all samples, but flavonoids were
      similar in M. affine and M. candidum. It suggests that both M. affine and M.
      candidum can be used for the Herba Melastoma.

PMID- 18074835
TI  - [HPLC fingerprint of Phlomis younghusbandii].
AB  - OBJECTIVE: To establish the characteristic fingerpint from Phlomis
      younghustbandii. METHODS: The different collecting time and county samples of
      Phlomis younghusbandii were determined by HPLC. RESULTS: The HPLC-FPC of Phlomis
      younghusbandii was set up by establishing 14 common peaks. Accuracy, stability
      and repeatability of the method were good. CONCLUSION: The peaks in the spectrum
      were all separated perfectly, which met the regulation of HPLC-FPC.

PMID- 18074836
TI  - [Study on HPLC fingerprint of water-soluble constituents of Carthamus
      tinctorius].
AB  - OBJECTIVE: To establish the HPLC-fingerprint of the water-soluble constituents of
      Carthamus tinctorius. METHODS: 18 samples of Carthamus tinctorius from different
      producing areas were determined by Agilent 1100 DAD-HPLC under the
      chromatographic conditions: column by SinoChrom ODS-BP (250 mm x 4.6 mm, 5
      microm), methanol-0.7% H3PO4 water with gradient elution, column temperature 30
      degrees C, flow rate by 1 ml/min, wavelength 280 nm, and inject volume 20 microl.
      RESULTS: The HPLC-fingerprint of the water-soluble constituents of Cartharnus
      tinctorius was established on the basis of 10 bitch of drugs from Xinjiang
      according to SPSS analysis. CONCLUSION: A reliable method is provided for the
      quality identification of Carthamus tinctorius.

PMID- 18074837
TI  - [Studies on the HPLC fingerprint spectrum of flavonoids in Gynostemma
      pentaphyllum].
AB  - OBJECTIVE: To establish the HPLC fingerprint spectrum of flavonoids from
      Gynostemma pentaphyllum. METHODS: The HPLC conditions with TURNER Kromasil C18
      column (250 x 4. 6 mm, 5 microm) was used, the mobile phase consisted of 0.4%
      phosphoric acid-methanol-acetonitrile with gradient elution at flow rate of 0.5
      ml/min and the detection wavelength was set at 360nm. RESULTS: Ten common
      characteristic peaks were taken as fingerprint peaks the presision and the retest
      are in accordance with the requirement. CONCLUSION: The method is stable,
      reliable, precision and provides a scientific basis for the quality standard of
      Gynostemma pentaphyllum.

PMID- 18074838
TI  - [The HPLC fingerprint analysis of Fructus citri].
AB  - OBJECTIVE: To study and establish the fingerprint of raw Fructus Citri by phased
      high performance liquid chromatography. METHOD: The chromatographic conditions
      were as follows: a Kromasil C18 column was used; the mobile phase was composed of
      methanol and acetic-water(3.1:100, v/v) with gradient elution; the flow rate was
      1.0 ml/min and the UV absorbance detection was set at 284 nm. RESULT: Under the
      selected chromatographic conditions, good HPLC fingerprints of Fructus Citri were
      obtained. CONCLUSION: Quality of raw Fructus Citri can be controlled effectively
      by HPLC fingerprint.

PMID- 18074839
TI  - [Alkaloid metabolites of mangrove endophytic fungus ZZF42 from the South China
      Sea].
AB  - Four compounds, apicidin (1), N-methylharman (2), cylo (Phe-Tyr) (3) and indole-3
      acetic acid (4) were isolated from the mangrove endophytic fungus ZZF42 from the
      South China Sea. Their structures were elucidated by spectral data. Compound 1
      was first isolated from the marine fungus. Compound 2 was firstly isolated from
      marine microorganism. Compound 1 exhibited selective in vitro cytotoxicity
      towards KB ahd KBv200 with IC50 values of less than 0.78 microg/ml.

PMID- 18074840
TI  - [Studies on the chemical constituents of the ethyl acetate portion of Nervilia
      fordii].
AB  - OBJECTIVE: To study the chemical constituents of the ethyl acetate portion in the
      herb of Nervilia fordii from guangxi. METHODS: The constituents were separated
      and purified by using column chromatography with silica gel. These compounds were
      identified by their physical and spectral data. RESULTS: Five compounds were
      isolated and identified as norleucine (crystal I), 24 (S/beta)
      dihydrocycloeucalenol-(E)-p-hydroxy cinnamate (crystal II) , rhamnocitrin
      (crystal III), rhamnazin (crystal IV), daucosterol (crystal V). CONCLUSION:
      Compounds I , II, III, IV, V were isolated from this plant for the first time.

PMID- 18074841
TI  - [Separation and determination of oleanolic acid and ursolic acid from Cornus
      officinalis by capillary electrophoresis].
AB  - A cycledextrin-modified micellar electrokinetic chromatography technique for
      separating and determination oleanolic acid and ursolic acid in the fruit of
      Cornus officinalis was developed. The two bio-active components was completely
      separated using a buffer containing 60 mmol/L SDS, 2.5 mmol/L NaH2PO4, 2.5 mmol/L
      Na2B4O7, 8 mmol/L DM beta-CD,8 mmol/L beta-CD and 30% (v/v) 2-propanol. The
      correlation cofficients of the linear calibration graphs for oleanolic acid and
      ursolic acid are 0. 9996 and 0.9995, respectively. The effects of SDS, 2
      propanol, dimethyl-beta-cyclodextrin, beta-cyclodextrin, NaH2PO4, Na2B4O7 and pH
      on separation were investigated.

PMID- 18074842
TI  - [Separation, purification and spectrum analysis of SHP].
AB  - Crude SHP was obtained from extracting with hot water and precipitating with
      ethyl alcohol. Free proteins were removed by trypsinase combined with Sevage
      method. Different fractions were got by gel filtration chromatography. The
      molecule structure was analyzed by ultraviolet spectrum scanning and KBr infrared
      spectroscope. The results showed that the reaction of phenol-sulfuric acid was
      postiive, reaction of ninhydrin was weak positive and reaction of iodine
      potassium iodide was negative, the extraction was regarded as a non-starch
      polysaccharide. Extraction rate of SHP was 8.56% and the content of
      polysaccharides was 90.96%. Gel filtration chromatography showed that SHP
      composed of furanopolysaccharides, xylose, galactose, arabinose, glucose,
      rhamnose and fructose. Ultraviolet spectrum showed that SHP contained little DNA
      and protein, infrared spectrum showed that SHP was main furanopolysaccharides and
      had beta-glycosidic bouds in its molecule structure, and there was a
      characteristic absorb peak of at-D-galactopyranosyl in it.

PMID- 18074843
TI  - [Studies on the chemical constituents of Gueldenstaedtia stenophylla].
AB  - OBJECTIVE: To study the chemical constituents of Gueldenstaeditia stenophylla.
      METHODS: The constituents were isolated by alcohol extraction, column
      chromatography on silica gel. Their structures were elucidated by chemical and
      spectroscopic methods. RESULTS: Six compounds were obtained, and five of them
      were identified as n-hexadecanioc acid (I), beta-sitosterol (II), daucosterol
      (III), apigenin (IV), D-fructose (VI). Compound V was being determined.
      CONCLUSION: Five compounds are isolated from Gueldenstaedtia stenophylla and
      compounds I, III are extracted from Gueldenstaedtia Fisch for the first time.

PMID- 18074844
TI  - [Chemical study of nucleosides on Cordyceps militaris].
AB  - OBJECTIVE: To investigate the nucleosides of Cordyceps militaris. METHODS: The
      primary extract technique of nucleosides from Cordyceps militaris was founded,
      the nucleosides were isolated by chromatography. RESULTS: Four compounds were
      isolated from the mycelium of Cordyceps militaris. They were identified as
      uridine (1), adenosine (2), guanosine (3) and p-tyrosine (4), respectively.
      CONCLUSION: Compounds 1, 2 and 3 are the main nucleosides in Cordyceps militaris.

PMID- 18074845
TI  - [Studies on chemical constituents of Heterosmilax yunnanensis].
AB  - OBJECTIVE: To study the chemical constituents of Heterosmilax yunianensis.
      METHODS: The compounds were isolated and repeatedly purified with chromatograph
      and the structures were elucidated by physico-chemical properties and spectral
      analysis. RESULTS: Eight compounds were obtained and elucidated as beta
      sitosterol (I), glycerol monopalmitate (II), daucosterol (IIl), hexacosanoic acid
      (IV), 5-hydroxymethyl furaldehyde (V), hergapen (VI), ursolic acid (VII),
      liquiritigenin (VIII). CONCLUSION: They have been isolated from this plant for
      the first time, and IV - VIII are obtained from the plants of Heterosmilax for
      the first time.

PMID- 18074846
TI  - [Influnce of Tinglizi on some neuroendocrine factors and type I and III collagen
      in ventricular remodeling induced by abdominal aortic banding in rats].
AB  - OBJECTIVE: To approach the influnce of Tinglizi on some neuroendocrine factors
      and type I and III collagen in ventricular remodeling induced by Abdominal Aortic
      Banding (AAB) in rats. METHODS: Myocardial hypertrophy ventricular remodeling
      model was induced by abdominal aortic banding (AAB) in rats. After 30 day
      treatment, the systolic blood pressure (SBP) diastolic blood pressure (DBP) were
      measured; Then the ratios of LVW/BW (left ventricle weight/body weight), HW/BW
      (heart weight/body weight) were calculated; The Angiotensin II (Ang II) and
      Endothelin (ET-1) content in heart tissue and the Aldosterone (ALD) concentration
      of blood plasma were determined by radioimmunoassay. The content of type I and
      III collagen in myocardium were determined using immunohistochemical analysis.
      Hydroxy proline content in heart tissue was measured by hydrolysis method.
      RESULTS: The experimental data demonstrated that Tinglizi could decrease SBP, DBP
      and the cardiac indexes of LVW/BW and HW/BW, significantly reduce the content of
      ANg II, ALD and ET, decrease the total collagen content and type I and III
      collagen (P<0.05). CONCLUSION: Tiglizi can significantly attenuate the
      experimental ventricular remodeling; the mechanism is related with its ability to
      inhibit the activation of rennin-angiontensin-aldosterone system (RAAS) and
      systema nervosum sympatheticum (SNS), decrease the content of neuroendocrine
      factors (Ang II , ET, ALD).

PMID- 18074847
TI  - [Influence of FPS on the expression of LDL-R mRNA in the liver tissues of
      hyperlipidemic rats].
AB  - OBJECTIVE: To explore the effect of FPS on low-density lipoprotein acceptor (LDL
      R) mRNA in the liver tissues of hyperlipidemic rats. METHODS: Sixty healthy male
      SD rats were randomly divided into six groups: normal control, model control,
      Gynostemma pentaphyllum, FPS low dosage, FPS moderate dosage, and FPS high dosage
      group. Excepting the rats in the normal control group, the ones in other groups
      were all made rats' hyperlipidemic model by irrigating hyperlipidemic emulsion
      into the stomach and observed the expression of LDL-R mRNA in the liver tissues
      of rats of each group. RESULTS: Relative content of LDL-RmRNA in low and moderate
      dosage groups was notably higher than that inmodel group. The contents's
      difference was not remarkable between FPS moderate dosage group and Gynostemma
      pentaphyllum group. CONCLUSION: FPS can appreciably increase the expression of
      LDL-R mRNA in the liver tissues of hyperlipidemic rats and promote the
      elimination ofLDL-C to reduce serum cholesterol notably.

PMID- 18074848
TI  - [Preparation of puerarin liposome and its oral absorption in rat].
AB  - OBJECTIVE: To prepare puerarin liposome and study its oral absorption in rat.
      METHODS: Liposome was prepared through the way of film dispersion-ultrasonic.
      Free puerarin in liposome suspension was separated from liposome through
      ultrafiltration, and then encapsulation ratio of liposome was determined. Micro
      morphology of liposme particles was observed under electronic transmission
      microscope. Puerarin concentration in blood was determined by HPLC. RESULTS: The
      encapsulation ratio of puerarin in liposome was 53%, and liposome particles were
      global or elliptical. The diameter range of liposome particies was from 50 nm to
      300 nm. The relative availability of puerarin liposme suspension to puerarin
      solution was 168%. CONCLUSION: Liposome as a drug carrier can enhance the oral
      absorption of puerarin in rat.

PMID- 18074849
TI  - [Variances of leptin mRNA in the adipose tissue of NAFLD rats intervened with the
      extracts of Polygonum cuspidatum compound].
AB  - The NAFLD rats were intervened with the extracts of Polygonum cuspidatum compound
      for 4 weeks. The reverse transcription and real-time quantitative polymerase
      chain reaction (RT-qPCR) methods were used to detecte the relative level of
      leptin mRNA in the adipose tissue of intervenient and control groups. Their
      variances of fat and glucose in serum were detected with the biochemical methods.
      The results showed that the level of leptin mRNA of intervenient group was
      significantly increased (P <0.05) and the triglycered and total cholesterol were
      significantly decreased (P <0.05). The extracts of Polygonum cuspidatum compound
      could increase leptin mRNA level in adipose tissue and improve the fat
      metablolism in serum. However, the serum glucose of the intervenient group was a
      little raised (P>0.05).

PMID- 18074850
TI  - [Pharmacological effects of volatile oil of Valeriana amurensis on CNS].
AB  - OBJECTIVE: To study the pharmacological effects of volatile oil of Valeriana
      amurensis on central nervous system. METHODS: The pharmacological effects of
      volatile oil of Valeriana amurensis on the autonomic activities of mice, the
      sleeping synergistic action of mice with pentoharbital sodium at subthreshold and
      hypnotic dosages, the sleep phases of rats, the writhing response of mice caused
      by acetic acid and the convulsion of mice induced by thio-semicarbazide were
      investigated. RESULTS: The autonomic activities of mice were significantly
      inhibited by the volatile oil of Valeriana amurensis. The rate of falling sleep
      and the extension of sleeping time of mice were significantly increased by the
      synergic action of pentobarbital sodium with the volatile oil. The sleep phases
      of SWS2 and REMS of rats were obviously extended by the volatile oil of Valeriana
      amurensis. In addition, the frequency of writhing response of mice caused by
      acetic acid was reduced, and the convulsion of mice induced by thio-semicarbazide
      was antagonized with the administration of the volatile oil. CONCLUSION: The
      volatile oil of Valeriana amurensis has significantly sedative analgesic and anti
      hyperspasmia effects.

PMID- 18074851
TI  - [Studies on antiproliferative effect of flavones compounds isolated from Yao herb
      medicines].
AB  - OBJECTIVE: To detect the cytotoxicity and in vitro antiproliferative effects of
      the flavones compounds isolated from some Yao herbal medicines, and analyze the
      basic structure-activity relationship. METHODS: The cytotoxicity on normal cells
      and antiproliferative effect on tumor cells were tested by MTT reduction assay
      respectively. RESULTS: Among the 6 flavones, the Eriodictyol-7-O-a-D-glucoside,
      Naringenin-7-O-beta-D-glucoside, quercetin and quercetin-3-O-beta-D-glucoside
      showed very low cytotoxicity to the two normal cells, Vero and MC cells, while
      the naringenin was high toxic to both of them. The eriodictyol was no toxic to
      Vero Cell but could affect MC cell at low concentration. The naringenin exhibited
      a wide-spectrum antiproliferative effect on all of the 7 tested cancer cell lines
      especially on the MCF-7 with low IC50 about 50 microg/ml. Among these cancer
      cells, the MCF-7 and HepG2 were more sensitive to the flavones compounds than the
      others. Both of them were inhibited by eriodictyol, quercetin and naringenin even
      at low test concentration. Furthermore, the antiproliferative effects of these
      compounds were concentration-related. CONCLUSION: Some of flavones compounds
      isolated from some Yao herb medicines showed high antiproliferative effect on
      cancer cells with low cytotoxicity on normal cells.

PMID- 18074852
TI  - [The empirical study of Maxingganshi decoction and its compatibility in acute
      lung injury rats].
AB  - OBJECTIVE: To explore the pharmacodyniamic action and the mechanism of action of
      the Maxingganshi decoction in acute lung injury rats in order to supply the
      pharmacology evidence to cure the SIRS-ALI of Maxingganshi decoction. METHODS:
      The study designed by orthogonal design. The SIRS-ALI model were Conseructed by
      the LPS intravenous injection and the effects of Maxingganshi decoction and it's
      different compatibilities to the SIRS-ALI model were observed. The experiments
      results were analvsised in order to reveal the compatibility rules of the
      Maxingganshi decocotion. RESULTS: Maxingganshi decocotion and its different
      compatibilities had good effects of prevention and cure the SIRS-ALI. The
      mechanism maybe concerned with the Maxingganshi decocotion can decrease the TNF
      alpha and increase the IL-10. The experiments results also indicated that the
      action of the full formula was the best. The principal drug was the most
      important in the formula. CONCLUSION: Maxingganshitang has a good effect in anti
      the ALI; the results indicat that the principal drug is the predominant
      therapeutic action in the formula ministerial drug. Adjuvant drug and messenger
      drug can strengthen pharmacodynamic action.

PMID- 18074853
TI  - [The role of apoptosis in herpes simplex virus I type myocarditis of mouse].
AB  - OBJECTIVE: To explore the relation among apoptosis of myocardial cell and the
      expression of TGF-beta1 in VMC. METHODS AND RESULTS: In the experiment, Viral
      myocarditis (VMC) in BALB/C mouse was obtained by inculating herpes simplex virus
      I type into abdominal cavity. The rate of VMC was 91.67% after 3 - 35 days of
      virus infection. The apoptosis (78.33%) and expression of TGF-beta1 (81.76%) were
      found in the myocardium of infected mouse by TUNEL and immunohistochemical method
      and electron microscope. AI of myocardial cell was 34.14+/-11.56 - 26.14+/-10.2.
      CONCLUSION: Apoptosis and expression of TGF-beta1 may participate in occurrence
      and development of VMC.

PMID- 18074854
TI  - [The protective effects of tenuigenin on the PC12 cells injury induced by H2O2].
AB  - OBJECTIVE: To study the protective effects of tenuigenin (TEN) on the PC12 cells
      injury induced by H2O2. METHODS: Oxidative damage PC12 cells model was induced by
      H2O2. The survival rate of the cells was determined by MTT method. The content of
      LDH was determined by ultraviolet spectrophometry and the content of MDA and SOD
      activity was measured respectively by thiobarbituric acid and xanthine oxidese
      method. RESULTS: tenuigenin could reduce obviously cells injury induced by H2O2.
      10 mg L(-1) tenuigenin could improve the cells survival rate, reduce LDH
      releasing and MDA content, increase SOD activity. CONCLUSION: tenuigenin have
      significantly potective effect on the PC12 cells injury induced by H2O2.

PMID- 18074855
TI  - [Study on separation and purification of total alkaloids from Macleaya cordata].
AB  - A method for separation and purification of total alkaloids from Macleaya cordata
      with macroporous resin was studied, with the content and recovery rate of total
      alkaloids as indexes. The results were as follows: The static adsorption capacity
      of AB-8 type resin was 104. 65 mg/g, the static elution ratio were 95.9% , the
      dynamic adsorption capacity of AB-8 type resin was 96.5 mg/g, the recovery rate
      was more than 91.24% and the purity was more than 90%. AB-8 type resin was the
      best for separating and purificating Macleaya cordata in total alkaloids. The
      optimum conditions is: the eluant is 90% alcohol and 2-3 times as the volume of
      the resin, the volume of the resin is 10.4 times of total alkaloids in sample,
      concentration of total alkaloids of sample is 21.57 mg/ml and current velocity of
      2-3 ml/min, pH value of sample is 7-8.

PMID- 18074856
TI  - [Study on purification of total flavonoids from Rosa laevigata with macroporous
      resin column chromatography].
AB  - OBJECTIVE: To Study the technologic conditions of purifying total Rosa laevigata
      by AB-8 pocket. METHODS: Extracting flavonoids from Rosa laevigata with 70%
      alcohol, the thick flavonoid powder were obtained and the content of pure
      flavonoids in it could be determinated using spectrophotometry. Taking the
      adsorption of the AB-8 pocket to Rosa flavonoids as the research object, the
      factors that affected the AB-8 resin static absorption and desorption were
      studied preliminarily. RESULTS: The result showed that the effect was perfect
      when the flavononid concentration in the liquid was 0.3 mg/ml, the loading amount
      was 120 mg with the adsorption-power 1 ml/ min; And the volume of 70% alcohol was
      eluant 5 BV with desorption-power 1 ml/min. The pure flavonoid content in thick
      flavonoid powder was 25.2% and it reached 42.2% after being purified by the AB-8
      pocket adsorption resin. CONCLUSION: It proved AB-8 pocket adsorption resin have
      a better effect on purification of the flavononids of Rosa laevigata.

PMID- 18074857
TI  - [Study on the extracting and dried process of Qinxiangzhixie enteric-coated
      tablet].
AB  - OBJECTIVE: To study the optimum extracting and dried process of Qinxiangzhixie
      enteric-coated tablet. METHODS: With the content of Aesculin and Aescaletin as
      factor, the optimum extraction process was selected with the orthogonal design.
      RESULTS: The optimum extraction process conditions were as: decocting for 2
      times, with water of 8, 6 times of the drug mixture respectively 1.5 h, 1.0 h
      respectively. The optimum decompression dried process conditions was as follows
      :60 degrees C, -0.08 pa. CONCLUSIONS: The experimental results provide the basis
      for the ascertainment of extraction process of Qinxiang enteric-coated tablet.

PMID- 18074858
TI  - [Study on the technique of ultrasonic wave extraction of triterpeneclucoside].
AB  - The extraction technique of ultrasonic wave on increasing the triterpeneclucoside
      was studied. Based on single factor experiments and the orthogonal design
      introduced,the optimized extracting conditions of triterpeneclucoside were
      investigated. The results showed that the best extraction technique conditons are
      65% alcohol-water, the ratio of solid to liquid 1:30,dousing over 30
      minutes,ultrasonic wave lasting for 40 minutes, ultrasonic frequency 26.8 KHZ,
      ultrasonic (output) power 1080 kw and extraction temperature 40 degrees C,
      respectively.

PMID- 18074859
TI  - [Contents mensuration of total alkaloid in Uncaria rhynchophylla by acid dye
      colorimetry].
AB  - OBJECTIVE: To investigate the method of determination of total alkaloids Uncaria
      rhynchophylla. METHODS: The Contents of total Alkaloid were determined by Acid
      dye Colorimetry. RESULTS: Acid dye color conditions: pH3.6 buffer 5.0 ml,
      bromocresol green liquid 5.0 ml; chloroform extraction three times, each time was
      exeracted for 2 minutes, put it aside for at least 5 minutes for the
      determination of the best method. Rhynchophylline 6.018 microg - 108.324 microg
      in the linear range, Recoveriys rate was 97.19%, RSD was 1.34% (n = 6).
      CONCLUSION: The method is simple, highly sensitive and reproducible.

PMID- 18074860
TI  - [Preparation and examination of the vitro releasing of pH-dependent kuijiekang
      tablet for colon-specific delivery].
AB  - OBJECTIVE: To prepare the pH-dependent kuijiekang tablet for colon-specific
      delivery used in treating the ulcerative colitis and to develop the in vitro
      release method of kuijiekang tablets. METHODS: The coating prescription was
      screened by the in vitro delivery of Puerarin and Berberine hydrochloride. The in
      vitro releasing property of the preparation was examined by the method of in
      vitro delivery. RESULTS: The preparation methods of the pH-dependent kuijiekang
      tablet for colon-specific delivery was obtained from the in-vitro delivery,
      Puerarin and Berberine hydrochloride were not detected in the simulated gastric
      fluid after 2 h and the quantitied of Puerarin and Berberine hydrochlo4de were
      less 10% in the simulated intestinal fluid after 4 h. The quantities of Puerarin
      and Berberine hydrochloride were 90.07% and 89.87%. CONCLUSION: It can be
      prepared and the preparation is a promising delivery system for drugs to be
      delivery to the colon.

PMID- 18074861
TI  - Molecular cytogenetic analysis of chromosome aberrations in desmoid tumors.
AB  - To date there are only few reports concerning chromosomal changes in desmoid
      tumors. To extend the knowledge in this field we examined 19 samples from the
      patients diagnosed with desmoid tumors. In the present study formalin-fixed and
      paraffin-embedded desmoid tumors were analyzed using fluorescence in situ
      hybridization (FISH) with a-satellite probes for chromosomes X, Y, 8 and 20.
      Chromosomal abnormalities were found in 6 cases, both abdominal and extra
      abdominal tumors. FISH studies revealed one case of trisomy 8 and trisomy 20. In
      four patients we have identified monosomy 20. Our findings confirm earlier
      reports concerning the diversity of chromosomal changes in desmoid tumors and
      might suggest that both groups of abdominal and extra-abdominal tumors are
      genuine neoplasms.

PMID- 18074862
TI  - Evaluation of retinoblastoma protein expression in endometrial hyperplasia.
AB  - In our study we investigated immunohistochemical expression of retinoblastoma
      protein (pRb) in physiological endometrium (n = 15), hyperplastic endometrium (n
      = 61) and post-hormone replacement therapy (HRT) endometrium (n = 24). METHODS:
      We performed an immunohistochemical analysis of pRb expression in 100 specimens
      of human endometrium. RESULTS: The average pRb immunoexpression index score in
      glandular endometrial cells and stromal endometrial cells were 57,699 and 21,191
      respectively. The less intense pRb immunostaining for the glandular cells was
      displayed in women over 49 years old. The most intense staining effect of
      glandular cells was observed among patients with physiological endometrium, no
      older than 49 years of life. There was no statistically significant correlation
      between the obtained pRb immunoexpression and clinical data of the examined
      patients. CONCLUSIONS: We conclude that immunohistochemistry is not sensitive and
      specific enough to reveal pRb alterations resulting in endometrium pathologies.
      Alternatively, pathological rearrangements of endometrium may be independent from
      the accuracy of the pRb control over restriction point in cell-cycle pathway.

PMID- 18074863
TI  - Relationship of P-cadherin expression to basal phenotype of breast carcinoma.
AB  - BACKGROUND: P-cadherin (P-CD) is a molecule expressed mainly by basal cells
      involved in cell adhesion. We evaluated expression of P-CD in operable breast
      carcinomas and its relationship with immunohistochemical markers of the basal
      like phenotype and with clinical outcome. MATERIAL AND METHODS: Expression of P
      CD was analyzed by immunohistochemistry in 194 tissue specimens of invasive
      operable ductal breast cancer. RESULTS: 112 cases (57.7%) were identified as
      being P-CD-positive. P-CD-positive tumors usually lacked steroid receptors (p =
      0.042), expressed basal type cytokeratins (p = 0.001), and were positive for
      cyclin E (p = 0.039). In a univariate analysis of cancer-specific survival with a
      median follow-up period of 58 months, P-CD expression was not associated with
      prognosis (5-year survival rate for positive vs. negative patients 67.0 vs.
      77.0%, log rank p = 0.121). CONCLUSION: P-CD may be regarded as an additional
      immunohistochemical marker of basal-like breast carcinomas. However, P-CD
      expression is not an adverse prognostic factor.

PMID- 18074864
TI  - The -173 G/C polymorphism of the promoter region macrophage migration inhibitory
      factor gene is not associated with incidence of pulmonary hamartoma.
AB  - Hamartomas are the third most common cause of solitary pulmonary nodule and the
      most common benign tumors of lung. Recent study indicated that hamartoma may be
      associated with a chronic inflammatory diseases. Histochemical analysis of the
      expression profile of growth-relevant was shown the upregulation of macrophage
      migration inhibitory factor (MIF) in hamartomas and surrounding lung parenchyma.
      We investigated polymorphism G/C at position -173 promoter gene of MIF, pro
      inflammatory cytokine in pulmonary hamartoma. This polymorphism of the MIF gene
      are association with increased production of MIF and have been found to confer
      increased risk of susceptibility to chronic inflammatory diseases. DNA samples
      were obtained from hamartoma tissue fixed with formalin, embedded in paraffin,
      from 52 patients and from blood samples of 123 sex and age matched healthy person
      served as control. The G/C polymorphism of MIF gene was determined by PCR-based
      AluI restriction fragment length polimorphism. The frequencies of the C allele
      did not differ significantly between pulmonary hamartoma patients and healthy
      controls (18% vs 15%, OR 1.26 CI95% 0.68-2.40). The obtained results suggest no
      association between G/C polymorphism at promoter gene of MIF and the incidence of
      pulmonary hamartoma, but our study has a preliminary character and should be
      extended on larger population.

PMID- 18074865
TI  - Increased mast cell density in renal interstitium is correlated with relative
      interstitial volume, serum creatinine and urea especially in diabetic nephropathy
      but also in primary glomerulonephritis.
AB  - In primary glomerulonephritis the degree of interstitial fibrosis governs the
      renal function. Mast cells participate in renal interstitial fibrosis, but its
      role remains poorly understood. Some of human mast cells contain chymase and
      chymase may participate in local angiotensin formation. Material consisted of 35
      renal biopsies. The diagnoses included diabetic nephropathy, mesangial
      glomerulopathy, IgA glomerulopathy and membranous glomerulopathy. Chymase and
      tryptase-positive cells were stained by immunohistochemistry and counted.
      Relative interstitial volume (RIV) was measured by point counting method. The
      density of tryptase-positive cells was 5.26 per 10 high power fields; the density
      of chymase-positive cells was 2.72. The counts were higher than in controls and
      highest in diabetic nephropathy. Creatinine serum level was related to density of
      chymase-positive cells (R = 0.57), density of tryptase-positive cells (R = 0.59)
      and RIV (R = 0.77). On multiple regression analysis creatinine level was
      influenced by RIV but also by density of chymase-positive cells. Our findings
      indicate that both types of mast cells are present in renal interstitium in
      diabetes and glomerulonephritis, and may influence the renal function. Chymase
      positive cells may be more important in this regard.

PMID- 18074866
TI  - Incidence of lymphomas in Poland. The national register data for 2006.
AB  - In Poland, data on the incidence and mortality associated with malignancies are
      collected by the National Cancer Register (NCR). The Register is based on the
      International Classification of Diseases (ICD-10), which does not allow for
      assessing the incidence of lymphatic neoplasms classified according to the WHO
      classification system enforced since 2001. Under the National Program of
      Combating Neoplastic Diseases that focuses on detection and diagnosing malignant
      lymphomas in Poland in order to record and precisely classify lymphatic
      neoplasms, in 2006, the Haematopathological Section of the Polish Society of
      Pathologists, acting in collaboration with the Polish Lymphoma Study Group,
      initiated a nationwide register of lymphatic malignancies, a continuation of the
      Register of Lymphomas for the Province of Malopolska. The register not only
      renders epidemiological data more specific, but also allows for a comprehensive
      quality control.

PMID- 18074867
TI  - Gastric solid glomus tumor and multiple glomangiomyomas of the large bowel with
      intravascular spread, multifocal perivascular proliferations and liver
      involvement.
AB  - The authors present a case of multiple glomus tumors (GTs) of the
      gastrointestinal tract, representing the type of a gastric glomus tumor proper
      and large bowel glomangiomyomas with myopericytoma-like features, observed in a
      46-year old female, with multifocal perivascular proliferations of primitive
      cells and hepatic involvement. Histologically, the multilobular gastric tumor and
      hepatic lesions corresponded to a typical glomus tumor, while the tumor situated
      in the transverse colon, up to 7 cm in diameter, presented as a glomangiomyoma
      infiltrative (with myopericytoma-like foci), and satellite tumors in the large
      bowel mucosa, 0.5-0.7 cm in diameter, represented small glomangiomyomas. In
      addition, the patient demonstrated two types of concomitant vascular lesions: 1/
      intravascular spread in the form of neoplastic plugs that obliterated the lumen
      of medium-size veins, and 2/ microscopic perivascular proliferation of primitive,
      small cells seen in the vicinity of the main tumor and in the adjacent adipose
      tissue. The patient has been ill for 2.5 years; she has been subjected to a
      partial colectomy with a resection of the small intestinal loop, greater omentum
      and the right ovary, followed by chemotherapy. At present, she is stable, and the
      infiltration--especially in the epigastric region--has decreased. The picture may
      confirm the theory that multiple GTs develop in association with multifocal
      proliferation of perivascular stem cells, as well as that their ability to
      penetrate into the lumen of large vessels gives origin to satellite tumors, which
      are not necessarily metastatic. It seems that at present, the group of
      perivascular SMA+ tumors may include infantile-type myofibromatosis in adults,
      myopericytoma, glomangio(myo)pericytoma, glomangiomyoma, glomus tumor proper, and
      glomangioma. Most likely, also some tumors previously classified as
      hemangiopericytomas belong to this group. The distinctive feature present in at
      least some of the above listed perivascular tumors is their synchronous or
      metachronous growth in a particular region and their ability to occupy
      intravascular space as nodules or solid bands, which in turn may give origin to
      satellite tumors. Multifocal lesions associated with a short survival in a given
      patient will obviously support the presence of metastatic disease. In the
      remaining cases, determination whether the patient has metastatic disease
      requires deep consideration and caution, also while deciding on treatment to be
      employed.

PMID- 18074868
TI  - Cleanup crew.

PMID- 18074869
TI  - An audit of intermittent pneumatic compression (IPC) in the prophylaxis of
      asymptomatic deep vein thrombosis (DVT).
AB  - This paper reports a prospective audit, against an existing baseline standard,
      for intermittent pneumatic compression (IPC) in the prophylaxis of asymptomatic
      deep vein thrombosis (DVT). This was done via a structured questionnaire, using
      the methodology of total population sampling, encapsulating all theatre staff
      within one NHS trust. With regards to the standard, performance is good, as IPC
      is DVT prophylaxis of choice in the perioperative area and is used frequently on
      most patients. The findings of the audit do, however, highlight the need for
      appropriate local DVT risk assessment guidelines, essential to ensure that
      prophylaxis is administered to the correct at risk groups, as prevention may be
      unjustified in low risk groups and possibly inappropriate for the same regimen to
      be used for all patients.

PMID- 18074870
TI  - The perioperative care of a super morbidly obese pregnant woman: a case study.
AB  - A super morbidly obese woman with a twin pregnancy presented to our hospital in
      Perth, Western Australia, for obstetric care. A caesarean section was planned for
      her, in order to ensure a safe, controlled manner of delivery. This article
      details the processes and procedures which had to be implemented in order to
      safely care for the patient during her perioperative experience.

PMID- 18074871
TI  - Minimally invasive surgery of the knee.
AB  - Minimally invasive knee replacement surgery has been developed in an attempt to
      lessen the impact of operations on the patient's quality of life, in the same way
      as arthroscopy, the forefather of minimally invasive surgery (MIS),
      revolutionised cartilage and ligament surgery three decades earlier. The
      technique is based on minimising soft tissue and muscle trauma, skin incision
      length, and capsular disruption while trying to maintain the ultimate goal of a
      well-aligned, well-fixed knee replacement. Short-term advantages including
      accelerated recovery and reduction in blood loss have been demonstrated, but it
      remains to be investigated whether MIS is able to provide sustainable benefits
      and long-term outcome equivalent to conventional surgery. Successful application
      of MIS techniques have been confirmed in conjunction with unicompartmental knee
      arthroplasty (UKR) implantation, while its use with total knee arthroplasty
      remains experimental. Critics have expressed concern that reduced visibility may
      compromise implant positioning and leg alignment which could have a negative
      effect on prosthetic long-term survival. MIS clearly represents a unique and more
      technically demanding procedure, but the learning curve may perhaps overshadow
      the benefits. Computer navigation may help to avoid such problems but so far
      scientific evidence regarding definitive outcomes is lacking, and some of the MIS
      techniques are still in the early phases of development.

PMID- 18074872
TI  - The soldier and the lady's lamp.

PMID- 18074873
TI  - [More work in the future, less free time].

PMID- 18074874
TI  - [Right time to recognize early warning signals].

PMID- 18074875
TI  - [High risk cases in the hospital: optimizing care and dangers].

PMID- 18074876
TI  - [Recommending early postoperative mobilization].

PMID- 18074877
TI  - [The place where the desire for more nursing education begins].

PMID- 18074878
TI  - [Mobile nursing service for old nd lonely people].

PMID- 18074879
TI  - [Dangerous "entertainments"].

PMID- 18074880
TI  - [From the performance to the interaction].

PMID- 18074881
TI  - [Psychoses and cannabis: a therapeutic approach].

PMID- 18074882
TI  - [Health in schools: a network which enriches the practice].

PMID- 18074884
TI  - [Profession/fire side: who has really changed?].

PMID- 18074883
TI  - [A new project sees the light].

PMID- 18074885
TI  - [Intuition. Tiny with an immense smile].

PMID- 18074886
TI  - [Environment as vision. The life and work of Jakob von Uexkulls (1864-1944)].

PMID- 18074887
TI  - Sustainability or collapse: what can we learn from integrating the history of
      humans and the rest of nature?
AB  - Understanding the history of how humans have interacted with the rest of nature
      can help clarify the options for managing our increasingly interconnected global
      system. Simple, deterministic relationships between environmental stress and
      social change are inadequate. Extreme drought, for instance, triggered both
      social collapse and ingenious management of water through irrigation. Human
      responses to change, in turn, feed into climate and ecological systems, producing
      a complex web of multidirectional connections in time and space. Integrated
      records of the co-evolving human-environment system over millennia are needed to
      provide a basis for a deeper understanding of the present and for forecasting the
      future. This requires the major task of assembling and integrating regional and
      global historical, archaeological, and paleoenvironmental records. Humans cannot
      predict the future. But, if we can adequately understand the past, we can use
      that understanding to influence our decisions and to create a better, more
      sustainable and desirable future.

PMID- 18074888
TI  - Managing climate change impacts to enhance the resilience and sustainability of
      Fennoscandian forests.
AB  - Projected warming in Sweden and other Fennoscandian countries will probably
      increase growth rates of forest trees near their northern limits, increase the
      probability of new pest outbreaks, and foster northerly migration of both native
      and exotic species. The greatest challenges for sustainable forestry are to
      restore and enhance the ecological and socioeconomic diversity of intensively
      managed forested landscapes. With appropriate management, climate warming may
      facilitate the regeneration of this diversity. Experimental transplant gardens
      along latitudinal or altitudinal gradients and high-resolution maps of expected
      future climate could provide a scientific basis for predicting the climate
      response of potential migrant species. Management of corridors and assisted
      migration could speed the movement of appropriate species.

PMID- 18074889
TI  - Ecosystem goods and services from Swedish coastal habitats: identification,
      valuation, and implications of ecosystem shifts.
AB  - Coastal areas are exposed to a variety of threats due to high population
      densities and rapid economic development. How will this affect human welfare and
      our dependence on nature's capacity to provide ecosystem goods and services? This
      paper is original in evaluating this concern for major habitats (macroalgae,
      seagrasses, blue mussel beds, and unvegetated soft bottoms) in a temperate
      coastal setting. More than 40 categories of goods and services are classified
      into provisional, regulating, and cultural services. A wide variety of Swedish
      examples is described for each category, including accounts of economic values
      and the relative importance of different habitats. For example, distinguishing
      characteristics would be the exceptional importance of blue mussels for
      mitigation of eutrophication, sandy soft bottoms for recreational uses, and
      seagrasses and macroalgae for fisheries production and control of wave and
      current energy. Net changes in the provision of goods and services are evaluated
      for three cases of observed coastal ecosystem shifts: i) seagrass beds into
      unvegetated substrate; ii) unvegetated shallow soft bottoms into filamentous
      algal mat dominance; and iii) macroalgae into mussel beds on hard substrate. The
      results are discussed in a management context including accounts of biodiversity,
      interconnectedness of ecosystems, and potential of economic valuation.

PMID- 18074890
TI  - Conflicts between biodiversity conservation and human activities in the central
      and eastern European countries.
AB  - Conflicts between the conservation of biodiversity and other human activities
      have been and continue to be of increasing concern in the European Union, often
      having important political, economic, and environmental repercussions. These
      conflicts have been addressed in the European Union by using a wide array of top
      down and bottom up tools, with varying degrees of success. A new challenge is now
      facing Europe with the integration of 10 new countries in the European Union (EU)
      and an additional range of biodiversity-rich habitats placed under EU
      legislation. The rich biodiversity of the central and eastern European countries
      (CEEC) is likely to be threatened by some aspects of the integration process, and
      conflicts between the conservation of biodiversity and other human activities are
      expected. In this paper, we review certain existing conflicts between
      biodiversity conservation and human activities in the CEEC, expected conflicts
      associated with integration to the EU, particularly in terms of new policy and
      legislation implementation, and, finally, explore possible conflict management
      options.

PMID- 18074891
TI  - Assessment of the potential of ecolabels to promote agrobiodiversity.
AB  - We conducted a study to assess to what extent current ecolabels contain standards
      that stimulate conservation and sustainable use of on-farm biodiversity of
      agricultural landscapes (agrobiodiversity). First, we developed an
      agrobiodiversity management yardstick to assess and compare the labeling schemes
      of ecolabels for arable farming. Key characteristics of the yardstick are the
      five levels linking the abstract notion of agrobiodiversity management to
      concrete measures on a farm and its foundation upon expert judgment regarding the
      effect of farming practices on agrobiodiversity. Several environmental themes,
      among them agrobiodiversity management, are regulated through the standards of
      labeling schemes of ecolabels. With the aid of this yardstick, the labeling
      schemes were scrutinized and the number, average efficacy, and compulsory nature
      of relevant standards was determined for 10 categories of farm management. The
      results show that all examined ecolabels contain at least some standards that
      stimulate conservation and sustainable use of agrobiodiversity, but there are
      large differences between the labels. We consider the results of the five
      ecolabels to be insufficient to warrant their usefulness as a governance strategy
      that the Dutch government could refer to and depend on as part of a national
      agrobiodiversity policy to stimulate agrobiodiversity.

PMID- 18074892
TI  - Environmental and economic evaluation of natural capital appropriation through
      building construction: practical case study in the Italian context.
AB  - This paper focuses on appropriation of natural capital through construction of
      buildings. The ecological footprint and the Costanza natural capital concepts are
      applied. The environmental consequences of human settlement are currently of
      great concern, and a need is felt to reduce the impact of building on the
      environment. The embodied energy of building materials and the "land area"
      required to sustain their production are considered to evaluate the demand on
      nature of this activity. The ecological footprints of 2 typical Italian buildings
      are compared. The paper also focuses on how to reduce the natural capital
      appropriation of building construction by means of environmentally inexpensive
      materials, renewable energy resources, and optimization of the use of
      bioproductive land by construction of multistoried buildings. Finally, to
      allocate an environmental load of buildings, an economic evaluation of natural
      capital appropriation through building construction is proposed.

PMID- 18074893
TI  - Increasing conservation management action by involving local people in natural
      resource monitoring.
AB  - There is a need for a better understanding of the status of the environment. At
      the same time, concerns have been raised regarding alienation of the local
      populace from environmental decisions. One proposed solution is participatory
      environmental monitoring. When evaluating the usefulness of environmental
      monitoring, the focus may be on accuracy, as is usually done by scientists, or on
      efficiency in terms of conservation impact. To test whether investment in
      participatory biodiversity monitoring makes economic sense for obtaining data for
      management decisions, we compared the cost efficiency of participatory and
      conventional biodiversity monitoring methods in Philippine parks. We found that,
      from a government perspective, investment in monitoring that combines scientific
      with participatory methods is strikingly more effective than a similar level of
      investment in conventional scientific methods alone in generating conservation
      management interventions. Moreover, the local populace seemed to benefit from
      more secure de facto user rights over land and other resources. Participatory
      biodiversity monitoring not only represents a cost-effective alternative when
      conventional monitoring is impossible, but it is also an unexpectedly powerful
      complementary approach, capable of generating a much higher level of conservation
      management intervention, where conventional monitoring already takes place.

PMID- 18074894
TI  - Declining populations of freshwater pearl mussels (Margaritifera margaritifera)
      are burdened with heavy metals and DDT/DDE.
AB  - Many aquatic mollusks, such as the freshwater pearl mussel (Margaritifera
      margaritifera), are in decline throughout Europe. The reasons are largely
      unknown; factors that have been suggested to contribute are river bed compaction
      due to agricultural practices, eutrophication, or pollutants of various natures.
      Brittle shells of recently deceased pearl mussels from northern Bavaria with weak
      calcium incrustations point to the possibility that calcium metabolism is
      affected. It is known that certain persistent organic pollutants and some heavy
      metals may induce calcium deficiency in wildlife. Elevated levels of the
      organochlorine insecticide DDT and its metabolite DDE, as well as of cadmium and
      some other heavy metals, have been found in pearl mussels. Both classes of
      environmental pollutants are known to potentially interfere with calcium
      homeostasis.

PMID- 18074895
TI  - An evaluation pattern for antimacrofouling procedures: Limnoperna fortunei larvae
      study in a hydroelectric power plant in South America.
AB  - The effects of global change and globalization of trade on the biosphere spur an
      increase in bioinvasions and their subsequent impact on ecosystems. Continental
      invading bivalves are important because of their impact on artificially
      constructed structures. Limnoperna fortunei was first found in the Neotropical
      region in 1991. Since then it has dispersed upstream in the Plata and Guaiba
      basins at a rate of 240 km y(-1). This species causes macrofouling in a manner
      similar to that caused by Dreissena polymorpha. This paper describes the biology
      of L. fortunei larvae from a hydroelectric power plant in South America. We
      suggest the importance of knowing the biology of the invading species and the
      need to consider the settlement patterns and densities of larvae in each of the
      sectors of the facility in order to achieve a sustainable prevention/control of
      macrofouling. This study acquires a global significance under the assumption that
      L. fortunei will eventually invade North America and Europe.

PMID- 18074896
TI  - Perceived importance of sustainability and ethics related to fish: a consumer
      behavior perspective.
AB  - Although sustainability and ethics are of increasing public importance, little
      research has been conducted to reveal its association with fish consumer
      behavior. Cross-sectional data were collected through a postal self-administered
      survey (June 2005) from a sample of 381 Flemish women aged 20-50 years. Consumers
      attach high perceived importance to sustainability and ethics related to fish.
      However, this perceived importance is neither correlated with fish consumption
      frequency nor with general attitude toward eating fish. Refusing to eat wild fish
      is grounded in sustainability and ethical concerns, whereas the decision not to
      eat farmed fish is associated with a lower expected intrinsic quality rather than
      shaped by importance attached to sustainability and ethical issues.

PMID- 18074897
TI  - Adaptive management of the Great Barrier Reef and the Grand Canyon world heritage
      areas.
AB  - Conventional perceptions of the interactions between people and their environment
      are rapidly transforming. Old paradigms that view humans as separate from nature,
      natural resources as inexhaustible or endlessly substitutable, and the world as
      stable, predictable, and in balance are no longer tenable. New conceptual
      frameworks are rapidly emerging based on an adaptive approach that focuses on
      learning and flexible management in a dynamic social-ecological landscape. Using
      two iconic World Heritage Areas as case studies (the Great Barrier Reef and the
      Grand Canyon) we outline how an improved integration of the scientific and social
      aspects of natural resource management can guide the evolution of multiscale
      systems of governance that confront and cope with uncertainty, risk, and change
      in an increasingly human-dominated world.

PMID- 18074898
TI  - Developing a predictive understanding of landscape importance to the Punan
      Pelancau of East Kalimantan, Borneo.
AB  - In order for local community views to be incorporated into new development
      initiatives, their perceptions need to be clearly understood and documented in a
      format that is readily accessible to planners and developers. The current study
      sought to develop a predictive understanding of how the Punan Pelancau community,
      living in a forested landscape in East Kalimantan, assigns importance to its
      surrounding landscapes and to present these perceptions in the form of maps. The
      approach entailed the iterative use of a combination of participatory community
      evaluation methods and more formal modeling and geographic information system
      techniques. Results suggest that landscape importance is largely dictated by
      potential benefits, such as inputs to production, health, and houses. Neither
      land types nor distance were good predictors of landscape importance. The grid
      cell method, developed as part of the study, appears to offer a simple technique
      to capture and present the knowledge of local communities, even where their
      relationship to the land is highly complex, as was the case for this particular
      community.

PMID- 18074899
TI  - Thirty years of land-cover change in Bolivia.
AB  - Land-cover change in eastern lowland Bolivia was documented using Landsat images
      from five epochs for all landscapes situated below the montane tree line at
      approximately 3000 m, including humid forest, inundated forest, seasonally dry
      forest, and cloud forest, as well as scrublands and grasslands. Deforestation in
      eastern Bolivia in 2004 covered 45,411 km2, representing approximately 9% of the
      original forest cover, with an additional conversion of 9042 km2 of scrub and
      savanna habitats representing 17% of total historical land-cover change. Annual
      rates of land-cover change increased from approximately 400 km2 y(-1) in the
      1960s to approximately 2900 km2 y(-1) in the last epoch spanning 2001 to 2004.
      This study provides Bolivia with a spatially explicit information resource to
      monitor future land-cover change, a prerequisite for proposed mechanisms to
      compensate countries for reducing carbon emissions as a result of deforestation.
      A comparison of the most recent epoch with previous periods shows that policies
      enacted in the late 1990s to promote forest conservation had no observable impact
      on reducing deforestation and that deforestation actually increased in some
      protected areas. The rate of land-cover change continues to increase linearly
      nationwide, but is growing faster in the Santa Cruz department because of the
      expansion of mechanized agriculture and cattle farms.

PMID- 18074900
TI  - Emigration and mortality of Black-necked swans (Cygnus melancoryphus) and
      disappearance of the macrophyte Egeria densa in a Ramsar wetland site of southern
      Chile.

PMID- 18074901
TI  - Environmental degradation in the Yellow River Delta, Shandong Province, China.

PMID- 18074902
TI  - Healing herbs and dangerous doctors: "fruit fever" and community conflicts with
      biomedical care in Northeast Thailand.
AB  - In Northeast Thailand, khai mak mai (fruit fever) is a local, ethnomedical
      category of illness identified by community members as untreatable by biomedical
      health providers. The illness is believed to be incompatible with several
      substances that may induce death, including fruit as well as two forms of
      medication associated with biomedical care: injections and intravenous solution.
      Consequently, fevers suspected of being khai mak mai are treated by herbalists
      while biomedical health services are avoided and feared. In this article, I
      examine local perceptions and treatment of khai mak mai. I also explore the
      context and consequences of concerns about the inadequacy of biomedical care, as
      well as the social meanings associated with the illness and the political
      economic context that shapes both the meanings of, and everyday responses to,
      fevers suspected of being khai mak mai.

PMID- 18074903
TI  - Critical therapeutics: cultural politics and clinical reality in two eating
      disorder treatment centers.
AB  - Recent studies suggest that eating disorders are increasing in Mexico and that
      this seems to correspond with Mexico's push to modernization. In this respect,
      Mexico exemplifies the acculturation hypothesis of eating disorders, namely, that
      anorexia and bulimia are culture-bound syndromes tied to postindustrial
      capitalist development and neoliberalist values, and that their appearance
      elsewhere is indicative of acculturation to those values. Available evidence for
      this claim, however, is often problematic. On the basis of five years of
      comparative fieldwork in eating disorder clinics in Mexico City and a small
      Midwestern city in the United States, I reframe this as an ethnographic question
      by examining how specific clinical practices at each site entangle global
      diagnostic categories with local social realities in ways that problematize
      existing epistemologies about culture and illness. In this regard, debates about
      acculturation and the global rise of eating disorders foreground issues of
      central epistemological and practical importance to contemporary medical
      anthropology more generally.

PMID- 18074904
TI  - Languages of labor: negotiating the "real" and the relational in Indo-Fijian
      women's expressions of physical pain.
AB  - Medical personnel in public clinics in Fiji routinely contend that state-funded
      medical resources are misallocated on patients who complain of, but do not
      actually experience, physical pain. Frequently, these patients are identified as
      being Indo-Fijian women (i.e., women of South Asian origin in Fiji). In this
      article, I examine clinical interactions between medical staff and female Indo
      Fijian patients to demonstrate how "real" and 'unreal' pain are distinguished in
      the clinical setting and to indicate some of the roles clinical encounters play
      in community processes that ascribe alternative meanings to physical pain.
      Focusing on how both physicians and women patients foster certain interpretations
      of physical pain over others, I argue that the category of 'unreal' pain, as
      employed by Fiji's physicians, consists of pain that medical professionals
      consider to be induced by psychological or physical, work-related stresses. I
      then show how Indo-Fijian women engage in a complementary but distinct discourse
      that emphasizes links between physical labor and pain and suggests that, in some
      cases, expressions of physical pain are as much an idiom of pride as an idiom of
      distress.

PMID- 18074905
TI  - The numerus clausus and its consequences.

PMID- 18074906
TI  - Decision making about operability in non-small cell lung cancer.
AB  - With the introduction of combined modality therapy and better staging techniques,
      the role of surgical resection for non-small cell lung cancer is continuously
      redefined. The final aim of surgical treatment for lung cancer is complete
      resection, also after neoadjuvant or induction therapy. Precise criteria for
      complete resection have recently been defined. Definite indications for surgery
      include clinical stages I, II and resectable IIIA. The precise role for surgical
      resection in stage IIIA-N2 lung cancer remains controversial but only downstaged
      patients should be considered. Stage IIIB is mostly treated by chemoradiotherapy.
      Accurate peroperative or surgical staging is necessary, as well regarding the
      tumour as nodal factor, to determine the extent of resection. A systematic nodal
      dissection should be performed including at least three hilar and three
      mediastinal lymph node stations. Post-induction surgical therapy often represents
      a greater technical challenge due to a pronounced hilar and mediastinal fibrosis.
      Downstaging is an important prognostic factor and persisting mediastinal lymph
      node involvement carries a poor prognosis. The optimal restaging method has not
      been established yet, but a pathological proof should be obtained.
      Remediastinoscopy is feasible with an acceptable accuracy but less invasive
      techniques are currently evaluated.

PMID- 18074907
TI  - Cryoplasty--where is the evidence?
AB  - Cryoplasty has been proposed as a more effective alternative to conventional
      percutaneous transluminal angioplasty in the management of peripheral vascular
      disease. In this review, we critically evaluate the current evidence to determine
      both the clinical efficacy and the technical issues with cryoplasty.

PMID- 18074908
TI  - Clinical application of topical sealants in liver surgery: does it work?
AB  - Hepatic resections are considered as a standard intervention in abdominal
      surgery. However there is still a remarkable complication rate. Despite all
      recent developments in surgical techniques during liver surgery, blood loss is
      still one of the main causes for postoperative morbidity and mortality. In
      addition to patient-dependent factors, aspects of the surgical technique play a
      major role, in particular with regard to the occurrence of peri-operative
      bleeding, fluid accumulation and bile leakage. Nowadays, the use of topical
      sealants is often recommended as an additional tool to decrease postoperative
      bleeding and bile fistula. Fibrin sealants are able not only to enhance clot
      formation and wound healing, but possibly work as a sealing device for the small
      biliary branches. In this overview we will try to evaluate the efficacy in terms
      of time to complete haemostasis, the need for blood transfusions and the
      incidence of bile leakage according to recent trials. Furthermore the clinical
      benefit for the liver surgery patient will be discussed.

PMID- 18074909
TI  - Occurrence of peripheral arterial disease in a Belgian cohort of patients with
      cardiovascular history of atherothrombosis.
AB  - RATIONALE: Peripheral arterial disease (PAD) is an underestimated and under
      diagnosed disease with as much as 60% of the patients having at least one other
      vascular bed affected. PURPOSE: The study aimed to evaluate the prevalence of PAD
      defined by different means in high risk Belgian ambulatory patients. METHODS:
      Participating physicians were to include a least six consecutive high risk
      ambulant patients for atherothrombosis. Demographical data and cardiovascular
      risk factors were recorded. The Edinburgh Questionnaire was administered. A
      vascular examination, including palpation and blood pressure measurement of the
      relevant arteries was performed. RESULTS: 275 Belgian physicians included a total
      of 2831 patients with a mean age of 68.0 years. Sixty three point three percent
      (63.3%) of the patients had a history of coronary artery disease whereas 28.0%
      reported a history of cerebrovascular disease. Overall, 1777 patients (62.8%, 95%
      CI: 61-65%) had a PAD diagnosis with an even distribution among males and females
      and increasing with age. PAD, defined as an ABI (Ankle Brachial Index) < 0.9, was
      detected in 28.5% of the population. PAD defined as the presence of intermittent
      claudication with positive Edinburgh Questionnaire or as a history of peripheral
      vascular revascularisation, was detected in 12.4% and 8.1% of the population
      respectively. Sixty six point seven percent (66.7%) of the PAD patients reported
      walking pain. The presence of pulsation of the tibialis posterior and/or dorsalis
      pedis arteries was not predictive of an ABI > 0.9. In contrast, the absence of
      pulse of both arteries was correlated with an odds-ratio of 6.4 to 8.1 to find a
      pathological ABI. CONCLUSION: The prevalence of PAD in ambulant patients with a
      history of coronary artery disease or cerebrovascular disease varied from 62.8%
      (composite of intermittent claudication with Edinburgh Questionnaire positive,
      history of peripheral vascular revascularisation, ABI < 0.9) to 28.5% (ABI <
      0.9). Sixty six point seven percent (66.7%) of the PAD population reported
      walking pain. The absence of pulsation of the tibialis posterior and dorsalis
      pedis arteries was correlated with an ABI < 0.9.

PMID- 18074910
TI  - Sleeve pneumonectomy for lung cancer--survival and complications (single-center
      experience with 42 patients).
AB  - BACKGROUND: Sleeve pneumonectomy is challenging both from the technical and
      oncological standpoint. The benefit of induction treatment is still under
      investigation. MATERIAL AND METHODS: The study included 42 patients with sleeve
      pneumonectomy for non-small cell lung cancer in an eight-year period. Right
      sleeve pneumonectomy was performed in 39 patients. Squamous cell and
      adenocarcinoma were found in 33 (78.5%) and 5 (11.9%) patients, respectively.
      Overall stage was IIIa for 25 (59.5%) and IIIb for 17 (40.5%) patients,
      respectively. RESULTS: Perioperative mortality and morbidity were 16.6% and
      35.7%. Leading cause of death was bronchopleural fistula. Five-year survival was
      35%. The survival difference between patients with NO+N1 versus N2 lesions was
      statistically significant (p = 0.01). There were no two-year survivors among
      patients with N2 lesions. Survival difference between T3 and T4 patients was also
      significant (p = 0.04). In a multivariate analysis, only T and N components were
      found significant in terms of prognosis. CONCLUSION: Sleeve pneumonectomy should
      be avoided in patients with N2 lesions confirmed preoperatively. A safe operation
      can be performed if the surgeon restricts airway resection to a maximum length of
      4 cm.

PMID- 18074911
TI  - Intraoperative high-dose-rate brachytherapy (IBT) for locally unresectable
      intraabdominal malignancy.
AB  - PURPOSE: Intraoperative high-dose-rate brachytherapy (IBT) has been successfully
      used in locally advanced unresectable intraabdominal malignancy. We
      retrospectively evaluated the safety, feasibility, and general outcome of IBT
      following cytoreductive surgery. PATIENTS AND METHODS: After radical resection,
      the target area to be treated by IBT was determined jointly by the surgeon and
      the radiation oncologist. A silicon template was used to position parallel hollow
      catheters spaced 1 cm apart against the area of interest. IBT doses were
      prescribed at 1 cm depth from the template surface and calculated using standard
      plans. Radiation was administered in a dedicated shielded room. RESULTS: Between
      August 2001 and February 2006, 10 patients (colorectal cancer n = 6, cervix
      cancer n = 1, extramedullar plasmocytoma n = 1, liposarcoma n = 1 and
      sacrococcygeal teratocarcinoma n = 1) were treated. The mean delivered IBT dose
      was 8 Gy (range 7.5-20). No postoperative mortality was seen, while major
      complications developed in one (10%) patient with a rectovaginal fistula and
      intraabdominal abscess. Five of the six colorectal cancer patients developed
      local recurrence while 3 also developed distant metastases. The mean disease-free
      and overall survival in this group was 8.5 months (range 4-15) and 25.5 months
      (range 10-48) respectively. Palliation of symptoms was observed in 89 % of cases.
      CONCLUSION: IBT combined with debulking surgery is feasible and can be safely
      performed. While cure is rarely achieved, IBT offers the potential to prolong
      local control and survival in locally unresectable intraabdominal cancer.
      Therefore, IBT can be considered as a valuable adjuvant in the therapeutic and
      palliative armamentarium in these selected patients.

PMID- 18074912
TI  - Routine pathological analysis of appendicectomy specimens--is it justified?
AB  - Appendicectomy for acute appendicitis is one of the most commonly performed
      surgical procedures. Our unit policy has been to conduct pathological examination
      of all resected specimens, however this practice has recently been questioned. We
      therefore sought to analyse the utility of routine histological examination of
      appendicectomy specimens. A consecutive series of 236 patients who underwent open
      appendicectomy for clinically suspected appendicitis was reviewed. Examination of
      the specimens revealed inflammation or necrosis in 175 (74%) of the cases-however
      unexpected histological findings were seen in 10 (4.2%) specimens. In five of
      these cases (2.1%), these findings resulted in a change in medical therapy. We
      conclude that appendicectomy specimens from patients with clinically suspected
      appendicitis show diversity in their histological characteristics; and that
      routine histological examination can yield clinically significant information in
      a significant minority of patients.

PMID- 18074913
TI  - Visualization of the normal appendix in children by non-contrast MDCT.
AB  - OBJECTIVE: We studied the proportion of normal appendices, identified on non
      contrast MDCT scans of the abdomen and pelvis in children with possible renal
      stones. MATERIALS AND METHODS: A total of 105 patients were included in the
      study, comprising 40 girls (38%) and 65 (62%) boys, with a mean age of 7.3 years.
      Non-enhanced abdominal computed tomographies were evaluated retrospectively, and
      the visualization, location, contents, diameter of the appendix, and the amount
      of abdominal fat were recorded. RESULTS: The appendix was clearly distinguished
      in 72 patients (68.5%). The difference in appendix visualization rates between
      patients with low and medium amounts of abdominal fat was statistically
      significant (p < 0.001). Visualization increased with age. The greatest external
      diameter was between 2.8 and 10 mm, with a mean of 5 +/- 1.34 mm. CONCLUSION:
      MDCT without contrast will be more useful when used in patients of 6 years old
      and over, for visualization of the appendix. A better visualization of
      retrocaecal appendix by MDCT provides a greater advantage over US. Prospective
      comparative studies will determine the role of this method in the diagnosis of
      acute appendicitis in pediatric patients.

PMID- 18074914
TI  - Treatment of rectal prolapse with radiofrequency ablation and plication--a new
      surgical technique.
AB  - BACKGROUND: This study was designed to assess the outcome of using a new
      technique of mucosal ablation using a radiofrequency device followed by its
      plication for rectal mucosal prolapse and to compare its results with the
      conventional ligature and excision procedure. MATERIALS AND METHODS: The
      procedure of radiofrequency ablation and mucosal plication (RAMP) is described. A
      Ellman radiofrequency generator was used for the procedure. Out of the 46
      patients with rectal mucosal prolapse, 24 patients were randomized to undergo
      ligature and excision procedure (LEP) and 22 were operated with RAMP. The
      operating time, amount of pain (VAS scale), postoperative analgesic requirement,
      time to return to work, wound healing period and postoperative complications were
      documented. RESULTS: Radiofrequency ablation and mucosal plication procedure on
      average resulted in short operation time (9 vs. 32 minutes, p < 0.05), shorter
      hospitalization (16 vs. 42 hours, p < 0.05) significantly less postoperative
      pain, fewer cumulative requests for analgesia by the patients (21 vs. 54 tablets,
      p < 0.05), earlier return to work (7 vs. 18 days, p < 0.05) and faster wound
      healing (14 vs. 35 days, p < 0.05) The complication rate was 9% with RAMP group
      and 29% with LEP group. CONCLUSION: The procedure of radiofrequency ablation and
      plication of mucosa shows promising results in patients with rectal mucosal
      prolapse. Being safe, effective, and a swift technique, it can be proposed as an
      improved alternative to conventional surgical procedure.

PMID- 18074915
TI  - Twenty years operating experience for popliteal artery aneurysm.
AB  - BACKGROUND: Is it better to treat popliteal aneurysms as elective operations when
      their diameter is above 2 cm? MATERIALS AND METHODS: Between 1985 and 2004, 76
      operations for popliteal artery aneurysm were performed in 67 patients. RESULTS:
      58 operations were elective (76.32%) and 18 were emergencies [13 procedures and 5
      urgent amputations] (23.68%). For reconstruction, autologous saphenous vein was
      used in 53 cases (69.74%), vascular prosthesis in 15 cases (19.74%), and a cryo
      preserved vein allograft in 3 cases (3.95%). In 5 cases (6.58%), amputation for
      advanced lower limb ischaemia was performed without arterial reconstruction. In
      our patient group there were 62 men (92.53%) and 5 women (7.47%). Patient age
      ranged from 49 to 80 years, with a mean age of 69 years. Elective operation was
      indicated in most of the patients with popliteal artery aneurysm, because it was
      associated with a relatively low risk for the patient. In fact, it was a
      preventive operation. In the acute stage, there was a higher risk of
      complications and (potential) amputation. CONCLUSIONS: Popliteal aneurysms should
      be surgically treated as soon as possible after their diagnosis, preferably
      before ischaemic complications occur.

PMID- 18074916
TI  - Mycotic aneurysm of the descending thoracic aorta. Review and case report.
AB  - A 74-year-old male presented with bilateral invalidating claudication. A
      bilateral percutaneous transluminal angioplasty (PTA) with stenting of both
      superficial femoral arteries was performed but complicated by an urosepsis with
      Escherichia coli and a septic phlebitis at the site of an intravenous line. The
      phlebitis was complicated by a local abcedation for which incision and drainage
      were performed. One month after discharge he was readmitted at our hospital with
      septic fever and positive hemocultures for Escherichia coli. Positron emission
      tomography-computed tomographic scan (PET/CT-scan) showed a mycotic aneurysm of
      the thoracic aorta. Because no cryopreserved donor aorta was available and the
      aneurysm size rapidly increased, an open in situ repair was performed with a
      Dacron silver prosthesis soaked in rifampicin. His recovery was further
      complicated by a perforated toxic megacolon for which a subtotal colectomy was
      performed. Further recovery was uncomplicated and 10 months after the aortic
      repair patient is still free from infection.

PMID- 18074917
TI  - Totally retroperitoneal laparoscopic aortobifemoral bypass.
AB  - The classic procedure for aortobifemoral bypass is open surgery. Since the first
      totally laparoscopic aortobifemoral bypass reported in 1997 by Yves-Marie Dion,
      laparoscopy has been accepted by several authors as a possible minimally invasive
      alternative for aorto-iliac occlusive disease. The transperitoneal left
      retrocolic and retrorenal ways are generally used. The totally retroperitoneal
      laparoscopic procedure has been described as an alternative to the
      transperitoneal approach. We report here a totally laparoscopic retroperitoneal
      approach to performing aortobifemoral bypass. This approach was proposed to a 51
      year-old man with aorto-iliac occlusive disease. There was no indication for
      endovascular revascularization. The patient suffered from 10 metres of bilateral
      intermittent claudication and lower limb ulcers. During the surgical procedure
      our patient was placed in a 30-degree right lateral decubitus position. The
      optical system was first placed in an intra-abdominal position to check the
      positioning of the trocars in the left retroperitoneal space. The dissection of
      the retroperitoneal space was performed by CO2 insufflation and by blunt
      dissection using laparoscopic forceps. The infrarenal aorta was exposed and
      clamped by laparoscopic clamps. A bifurcated graft was sutured on the left-hand
      side of the aorta by a running suture. Both prosthetic limbs were tunnelized
      retroperitoneally to the groin under optical control. The femoral anastomoses
      were performed by classic open surgery.

PMID- 18074918
TI  - Unrecognized traumatic bilateral diaphragmatic rupture and aortic rupture.

PMID- 18074919
TI  - Cystic lesions in the liver: benign or malignant?
AB  - A 65-year old patient is presented with an ultrasound showing multiple cysts in
      liver and both kidneys. Computed tomography scan (CT-scan) showed a cyst in the
      right liver lobe with a largest diameter of 12 cm, suspicious for
      cystadenocarcinoma. Further staging showed no extrahepatic metastasis.
      Considering possible malignancy, aspiration of the cyst was not an option because
      of the risk for ent-metastasis. Resection of the tumour was considered as the
      best treatment. Peroperatively the cyst was localized with ultrasound, after
      which an extended right hepatectomy was performed. No peroperative complications
      occurred. Histological diagnosis was a cyst, originating in dilated von Meyenburg
      complexes. No signs of a biliary cystadenoma or malignant deformation were
      observed. A CT-scan 1 year postoperatively showed some other small cysts in the
      left liver lobe, the patient was free of any complaints. The differential
      diagnosis in cases of asymptomatic liver cysts will be discussed.

PMID- 18074920
TI  - Classical operative therapy for Zenker's diverticulum.
AB  - Zenker's diverticulum is a rare disease usually described in elderly patients.
      The "gold standard" is endoscopic treatment. We describe a 77-year-old patient
      treated by classical operative therapy. Patient history showed weight loss of 22
      kilograms within a year. Physical examination showed a swelling in the neck of 7
      by 2 centimeters. Gastroscopic examination demonstrated a Zenker's diverticulum,
      but this could not be passed with the scope. Classical surgical resection was
      performed with excellent results 6 months after surgery.

PMID- 18074921
TI  - Spontaneous gastric rupture in non-neonatal children: a case report.
AB  - This case reports an idiopathic gastric rupture in a 3-year-old girl who had an
      episode of nausea and vomiting after a large meal. Abdominal ultrasound and CT
      scan revealed free air and fluid in the abdominal cavity, leading to the
      diagnosis of gastro-intestinal perforation. During emergency surgery, gastric
      rupture was detected on the anterior wall of the gastric body near the greater
      curvature and treated by performing a sleeve gastrectomy. The intra-operative
      course was complicated by a cardiac arrest. The child survived following
      intensive postoperative care. All articles on spontaneous idiopathic gastric
      rupture in pre-school age children have only been reported in Japanese and
      Chinese literature.

PMID- 18074922
TI  - Bowel perforation from ingested blister-pack.

PMID- 18074923
TI  - Chronic anal fissure from suspected adult sexual abuse in a traumatic anal sex
      practice patient.
AB  - The aetiopathogenesis of chronic anal fissure (CAF) is unclear and is probably
      multifactorial. CAF represents 10-15% of proctological consultations. This case
      report identifies adulthood sexual abuse as a significant risk and a potential
      aetiopathogenic factor of CAF This case history was discovered while carrying out
      administrated interviews during authors' clinical retrospective study on CAF. The
      clinical presentation of this 49-year-old woman is predominated by chronic anal
      lesions (anal tears in the anoderm, anal sphincter hypertrophy), associated
      medical history as a high consumer of healthcare with very poor mental health,
      chronic traumatic anal sex practice history, and especially persistent
      recurrences of gastro-intestinal symptoms after surgery. Surgical history is
      summarized as: 7x spontaneous abortion; 5x fistulectomy and 3x anal abscess; 4x
      Bartholin's gland; 4x hypertrophy papilla ablation; 2x anal manometry, 2x
      fissurectomy and 1x sphincterotomy; 2x haemorrhoid; and 1x hysterectomy. These
      symptoms initially started and the operations in particular took place after she
      was married. After 26 years of sexual abuse within her marriage, the clinical
      diagnosis was made and was consented by this patient. A referral to a
      psychiatrist was evident and a long course of multidisciplinary therapy (medical,
      surgical, physiological and psychological approaches) seemed to be of benefit, in
      terms of improving the clinical symptoms. Authors suggest that physicians should
      suspect sexual abuse in any patient with a medical history as a high consumer of
      healthcare and especially when there is persistent recurrence after the lateral
      subcutaneous internal sphincterotomy. We recognise that the link or causality is
      difficult to prove and further study is probably needed to shed light on the link
      between sexual abuse and CAF: although in the United Kingdom, over 20.83% of the
      population are subject to sexual abuse. 83%.

PMID- 18074924
TI  - Hydatid cyst of the breast.
AB  - Cystic hydatid disease is caused by the Echinococcus granulosus parasite. Most
      frequently, cysts develop in liver and lung. The breast is rarely a primary site
      of the hydatid cyst. A case of hydatid cyst of the breast is presented, the
      diagnosis of which was missed both pre-operatively and intra-operatively.

PMID- 18074925
TI  - Alveolar hydatid disease: imaging findings and surgical approach.
AB  - PURPOSE: We report six cases of Alveolar Hydatid Disease (five in the liver and
      one in the gastrosplenic ligament invading the spleen) in which curative
      resection of the liver (five cases) and splenectomy (one case) were performed.
      MATERIAL AND METHODS: The records of the six patients with AHD were
      retrospectively evaluated. Demographics of the patients, symptoms, laboratory
      findings, including serology were recorded. Imaging studies determined the extent
      of the disease preoperatively. Classification of the lesions was done according
      to the PNM (P = parasitic mass in the liver, N = involvement of neighbouring
      organs, and M = metastasis) staging system designed by the World Health
      Organization. All the surgical procedures were performed as complete resections,
      where negative margins were approved by frozen sections. Chemotherapy with
      albendazole (10 mg/kg/day) was continued postoperatively for two years in five of
      the six patients who were alive. RESULTS: All of the cases were from East
      Anatolia of Turkey, which is an endemic region. The mean age was 39.6 years (15
      54 years). Major complications occurred post-operatively in all patients,
      possibly due to the extensive resection. No recurrence was seen during the 5 year
      follow-up of two cases and 2 year follow-up of three cases. CONCLUSION: The
      treatment of Alveolar Hydatid Disease is curative radical resection. Thus, pre
      operative imaging studies to determine the extent and stage of the disease are of
      crucial importance.

PMID- 18074926
TI  - Ventral hernia repair: a practical point of view.

PMID- 18074927
TI  - Systemic peritoneal cavity lavage: a new strategy for treatment of the open
      septic abdomen.
AB  - INTRODUCTION: Management of the open abdomen is a challenge, certainly when
      fistulisation is present. This paper presents a new treatment modality for this
      specific situation. METHODS: Abdominal sepsis increases the net flow across the
      peritoneum to 300-500 ml/h. This flow was used to clean and flush the abdomen.
      Meropenem was administered, as antibiotic concentration in the peritoneal cavity
      is known to reach therapeutic levels after 8 hours. The abdominal fluid was
      captured using the abdominal VAC system and additional drains. The total amount
      of drained fluid was compensated intravenously. Thus, the concept was named
      "Systemic Peritoneal Cavity Lavage" (SPCL). RESULTS: Four patients with an open
      abdomen and severe abdominal sepsis were treated with SPCL and got out of their
      septic state within two weeks despite fistulisation and ongoing bowel leakage in
      three patients. A partial enterectomy with removal of the fistulas could be
      performed six weeks later. CONCLUSION: SPCL is a promising method to treat
      patients with severe abdominal sepsis. In combination with the fistula isolation
      technique it permits delayed treatment of fistulas in a hostile abdomen where
      immediate removal of the septic focus is impossible.

PMID- 18074928
TI  - The death of Napoleon III. Medical errors at the sickbed of an emperor.

PMID- 18074929
TI  - Get informed consent for risky drugs.

PMID- 18074930
TI  - Keep more of your practice income.

PMID- 18074931
TI  - Coping with tough markets: doctors battle a health plan monopoly.

PMID- 18074932
TI  - Health plan ignorance can cost you.

PMID- 18074933
TI  - Partner or employee: how to decide.

PMID- 18074934
TI  - The doctors' lounge moves online.

PMID- 18074935
TI  - Palatine tonsillar metastasis from lung adenocarcinoma.
AB  - Tonsillar metastasis from lung cancer is an extremely rare event and is usually
      related to metastatic spread of the neoplastic disease to other organs with poor
      prognosis. We present the unusual case of a 71-year-old man who developed a huge
      metastasis to the left palatine tonsil from a lung adenocarcinoma. The tumor was
      exophytic with necrotic and hemorrhagic areas, occupying a large portion of the
      oropharynx and producing airway obstruction, thus necessitating tracheostomy.
      Radiation therapy was delivered in an attempt to reduce the size of the tumor.
      Although a mild decrease of the tonsillar mass was noted, the designed therapy
      had to be discontinued because of a rapid deterioration of the patient's general
      condition. The patient finally died of disseminated disease. This case highlights
      the need for a thorough evaluation of a suspicious tonsillar enlargement, as this
      may be a sign of a primary malignancy elsewhere in the body.

PMID- 18074936
TI  - Update in the treatment of locally advanced breast cancer: a multidisciplinary
      approach.
AB  - Locally advanced breast cancer represents a wide variety of neoplasms and
      constitutes approximately 10%-20% of the newly diagnosed breast cancers. These
      cancers may have widely different clinical and biological characteristics.
      According to the American Joint Committee on Cancer (AJCC) staging system, all of
      stage III disease is considered locally advanced. The clinical treatment of
      locally advanced breast cancer is complex and should be tailored to the
      individual patient. In this paper we discuss the options of management of locally
      advanced breast cancer, focusing on a multidisciplinary approach through a
      combined-modality care involving surgery, radiotherapy and systemic therapy.

PMID- 18074937
TI  - A case-control study comparing methylene blue directed biopsies and random
      biopsies for detecting pre-cancerous lesions in the follow-up of gastric cancer
      patients.
AB  - OBJECTIVES: To compare the accuracy of Methylene Blue (MB) targeted biopsies with
      random biopsies in detecting intestinal metaplasia and dysplasia in the follow-up
      of patients after gastrectomy for gastric cancer. METHODS: Thirty patients (21
      Billroth II, 9 Billroth 1) for cancer, referred to the Gastroenterology Unit for
      an elective esophagogastroduodenoscopy (EGD), were enrolled. All endoscopies were
      performed with a high-resolution videoendoscope with an adjustable image
      magnification: EG-485ZH (Fujinon, Omiya, Japan). During EGD three random biopsies
      were taken in the stomach and, after staining with MB, three targeted biopsies
      were taken from every stained area. RESULTS: In 28 patients traditional endoscopy
      showed hyperemia of the anastomosis, in 2 patients a lesion. After MB in 6/30
      there were stained area (2 lesions seen with traditional endoscopy and 4 blue
      areas in other patients). As regards histology: 24 patients showed inflammation,
      while 2 patients with alterations in traditional endoscopy and with MB showed
      metaplasia and high grade dysplasia. In 4/30 (13.3%) patients MB guided biopsies
      showed significant lesions (3 intestinal metaplasia, 1 low grade dysplasia) while
      random biopsies showed only inflammation. CONCLUSIONS: After partial gastrectomy,
      the mucosa of the residual stomach usually undergoes severe changes, and these
      lesions are known to be pre-cancerous. The diagnostic accuracy of the MB
      technique seems to be superior to random biopsies for identification of
      intestinal metaplasia, dysplasia, and may be helpful in targeting biopsies and
      early endoscopic treatment.

PMID- 18074938
TI  - Thromboembolic risk after knee endoprosthesis.
AB  - Thromboembolic complications are the most frequent associated pathologies after
      knee replacement. The secondary deep vein thrombosis in the knee arthroplasty is
      often low symptomatic or asymptomatic and, sometime, it could lead to fatal
      pulmonary embolism. This is the main purpose recommending an antithrombotic
      prophylaxis. In this study 214 patients operated for knee arthroplasty and
      receiving low molecular heparin therapy were enrolled. They were clinically and
      echo/radiologically monitored for thromboembolic and/or hemorrhagic complications
      on the 2nd, 7th, 14th and 45th day from surgery. Results showed that only 45% of
      the cases developed DVT (deep vein thrombosis) out of which 17% could be
      objectively verified by ultrasonography and phlebography. In only one case
      massive pulmonary embolism with fatal evolution was discovered. It was not found
      any major bleeding except in four cases in which local haematomas were discovered
      (most probably related to anticoagulant treatment). This study concluded that the
      administration of low molecular weight heparin after knee arthroplasty
      significantly reduces the risks of thromboembolism in conditions where the
      increase of hemorrhagic complications doesn't result statistically significant.

PMID- 18074939
TI  - Current recommendations for the pharmacologic therapy in Kawasaki syndrome and
      management of its cardiovascular complications.
AB  - Kawasaki syndrome is a potentially life-threatening disease of early childhood
      that untreated holds a risk of severe coronary involvement. Its diagnosis is made
      via a list of clinical signs because etiology and pathophysiology are still
      unknown and no specific laboratory tool is available. Appropriate therapy with
      intravenous immunoglobulins and aspirin reduces the incidence of coronary
      abnormalities to less than 5%. Immunoglobulins have been shown to be highly
      effective in reducing disease symptoms or their severity and chiefly in reducing
      the rate of coronary artery aneurysm development. Aspirin is firstly used in high
      dose for its anti-inflammatory properties and then in low dose for its anti
      thrombotic effects. Timely diagnosis and precociously administered treatment are
      two crucial points in the definition of prognosis for Kawasaki syndrome. In this
      review heart complications are discussed and therapeutic options stratified
      according to both severity of coronary involvement and grading of cardiovascular
      risk.

PMID- 18074940
TI  - Oxidative stress tests: overview on reliability and use. Part I.
AB  - Monitoring oxidative stress in humans is achieved by assaying products of
      oxidative damage or by investigating the potential of an organism, tissue or body
      fluids to withstand further oxidation. Unfortunately, there is little consensus
      concerning the selection of parameters of oxidative stress or antioxidant state
      to be determined in defined patients or diseases. This is not only due to the
      uncertainty wheter or not a certain parameter is playing a causative role.
      Moreover, the methods of determination described in the literature represent very
      different levels of analytical practicability, costs, and quality. Generally
      accepted reference ranges and interpretations of pathological situations are
      lacking as well as control materials. At present, the situation is changing
      dramatically and sophisticated methods like HPLC (High Performance Liquid
      Chromatography) and immunochemical determinations have become more and more
      common standard.

PMID- 18074941
TI  - Endoscopic management of symptomatic choledocholithiasis in pregnancy without the
      use of radiations.
AB  - We report a case of 26-year-old woman at 10th week of gestation with cholestatic
      jaundice due to a common bile duct (CBD) stone managed by endoscopical retrograde
      cholangiopancreatography (ERCP). The procedure was successfully carried out
      without the use of ionizing radiations and under trans-abdominal
      ultrasonographical (US) control. A few cases are reported in literature in which
      ERCP was performed without fluoroscopy examination. We believe that ERCP with US
      guidance is an effective and safe procedure to treat symptomatic
      choledocholithiasis in pregnant women.

PMID- 18074942
TI  - Randomized, double blind placebo-controlled trial: effects of myo-inositol on
      ovarian function and metabolic factors in women with PCOS.
AB  - Oligomenorrhea and polycystic ovaries in women are one of the most important
      causes of the high incidence of ovulation failure. This is linked, perhaps, to
      insulin resistance and related metabolic features. A small number of reports show
      that myo-inositol improves ovarian function, but in these trials the quality of
      evidence supporting ovulation is suboptimal. Furthermore, few of them have been
      placebo-controlled. The aim of our study was to use a double-blind, placebo
      controlled approach with detailed assessment of ovarian activity (two blood
      samples per week) to assess the validity of this therapeutic approach in this
      group of women. Of the 92 patients randomized, 47 received 400 mcg folic acid as
      placebo, and 45 received myo-inositol plus folic acid (4 g myo-inositol plus 400
      mcg folic acid). The ovulation frequency assessed by the ratio of luteal phase
      weeks to observa-tion weeks was significantly (P < 0.01) higher in the treated
      group (25%) compared with the placebo (15%), and the time to first ovulation was
      significantly (P < 0.05) shorter [24.5 d; 95% confidence interval (CI), 18, 31;
      compared with 40.5 d; 95% CI, 27, 54]. The number of patients failing to ovulate
      during the placebo-treatment period was higher (P < 0.05) in the placebo group,
      and the majority of ovulations were characterized by normal progesterone
      concentrations in both groups. The effect of myo-inositol on follicular
      maturation was rapid, because the E2 circulating concentration increased over the
      first week of treatment only in the myo-inositol group. A significant increase in
      circulating high-density lipoprotein was observed only in the myo-inositol
      treated group. Metabolic risk factor benefits of myo-inositol treatment were not
      observed in the morbidly obese subgroup of patients (body mass index > 37). After
      14-wk myo-inositol or placebo therapy, no change in fasting glucose
      concentrations, fasting insulin, or insulin responses to glucose challenge was
      recorded. There was an inverse relationship between body mass and treatment
      efficacy. In fact a significant weight loss (and leptin reduction) (P < 0.01) was
      recorded in the myo-inositol group, whereas the placebo group actually increased
      weight (P < 0.05). These data support a beneficial effect of myo-inositol in
      women with oligomenorrhea and polycystic ovaries in improving ovarian function.

PMID- 18074943
TI  - Post-endoscopic polypectomy delayed bleeding concomitant with an abdominoperineal
      resection: a case report.
AB  - We describe the case of a delayed bleeding that occurred concomitantly with an
      abdominoperineal resection. The patient underwent endoscopy without apparent
      complications. During surgery, and in the immediate postoperative hours, 4 blood
      units were required to achieve stable conditions even if the surgical technique
      was correct, no major bleeding occurred and no blood was seen inside the lumen at
      bowel transection. On the 7th postoperative day (9th from polypectomy) the
      patient shocked for the first time. Two days later, massive clots appeared from
      the stoma and he shocked again. CT scan found the bleeding occurring from the
      polypectomy site and angiographic embolization finally ended the hemorrhage. The
      increased risk of delayed hemorrhages and their dramatic clinical manifestations
      render the post-polypectomy "window" period worth to be followed-up strictly. We
      believe that further invasive procedures, especially major surgery, should be
      postponed unless emergent and necessary to save the patient's life.

PMID- 18074945
TI  - On a higher plane. Medical center advances with Planetree model.

PMID- 18074946
TI  - Finders keepers. Planning for a hospitalwide RFID system.

PMID- 18074944
TI  - A case of multiple (eight external openings) tubercular anal fistulae. Case
      report.
AB  - We report a case of multiple fistulae in ano [8 external openings] in a 45-yrs
      old man, who had a history of episodes of pain and pus discharge from openings
      around the anus since 4 years. Biopsy from the tract of one of the fistula
      confirmed tubercular infection. He underwent radiofrequency fistulotomy using a
      Ellman radiofrequency device along with anti-tubercular treatment, which resulted
      in complete resolution, and healing.

PMID- 18074947
TI  - Outpatient odyssey. Ambulatory facilities mirror hospital interior trends.

PMID- 18074948
TI  - Hitting the target. Ten steps for developing a successful capital construction
      budget.

PMID- 18074949
TI  - Ready for anything. A look at the Joint Commission's new emergency management
      standards.

PMID- 18074950
TI  - Making do with less. Tools, equipment and products to improve department
      efficiency.

PMID- 18074951
TI  - [Infections of the urinary tract caused by permanent catheterization. Natural
      history, infective mechanisms and prevention strategies. An overall review based
      on our clinical experience and research].
AB  - Permanent drainage of the urinary tract by catheters or tubes causes bacteriuria.
      The potential harmful effects of the indwelling catheter's bacteriuria are
      related to: time since the insertion of the catheter; location of the catheter
      (urethra, bladder, kidney); catheter composition (latex, silicone, etc.); type of
      ineffective bacteria and specific pathogenic mechanisms; health status of the
      urinary tract being drained (prior radiation therapy, tumors, etc.); patient's
      health status (diabetes, immunodeficiency) and mobility; incidents and
      manipulations of the catheter, such as obstruction, irrigation, or retrieval. The
      evaluation of all mentioned factors enables strategies for prevention of septic
      episodes in relation with indwelling catheters, strategies that can be
      individualized for greater efficiency. Despite these preventive measures,
      infections secondary to the indwelling catheter may cause extremely severe septic
      episodes. Today, the indwelling catheter bacteriuria constitutes the greater
      source of nosocomial infection and its prevention and treatment a health care
      action of the highest importance. The study of mechanisms implied in the
      formation of biofilms, their pathogenic potential and preventive measures have
      been an attractive field of clinical and experimental research over the last
      years. The objective of this review is to make a synthesis of the works performed
      by our group.

PMID- 18074952
TI  - APC panel: don't finalize plan for observation packaging.
AB  - As the debate on packaging of observation charges nears a climax, understand your
      facility's patient mix and admission policies in order to predict the likely
      impact and prepare for the changes ahead. If your facility's policy is to admit
      elderly patients with chest pain, then the packaging of observation charges would
      have little impact on your department. If you normally send all chest pain
      patients for observation in a separate unit, increase your efforts to work
      cooperatively with other units to improve throughput. Inpatient admissions could
      increase significantly. If APC panel's recommendations are followed, it should be
      "business as usual" for your ED.

PMID- 18074953
TI  - Despite longer wait times, satisfaction still improves.
AB  - A new survey from Press Ganey Associates shows that ED managers are becoming
      increasingly adept at implementing strategies to improve communications with
      patients, which in turn, increases satisfaction. Here are some approaches
      recommended by ED managers: * Apologize for long waits, and do not get into an
      argument with the patient over the delay. * Use announcements in the waiting room
      and signs in patients' rooms to announce long waits, and keep patients updated. *
      Always overestimate the time it will take to obtain test results.

PMID- 18074954
TI  - Decrease liability risks of sedation in your ED.

PMID- 18074955
TI  - Major liability risk with procedural sedation.

PMID- 18074956
TI  - OIG advisory opinion clarifies some call issues.
AB  - Although the advisory opinion issued by the Department of Health and Human
      Services' Office of Inspector General (OIG) specifically states it only applies
      to the pay-for-call arrangement at one hospital, experts say the ED manager can
      use the opinion to establish bench-marks for their own on-call arrangements. * At
      the very least, the OIG has made it clear that paying for on-call coverage is not
      in and of itself a violation of any statutes. * Any per diem rates paid to ensure
      that specialists agree to take call must be "reasonable" and meet "fair market
      value." * The fact that the specialists also may be paid for the services they
      provide may not necessarily mean your arrangement is improper.

PMID- 18074957
TI  - Practice of rheumatology in Africa: challenges and opportunities.

PMID- 18074958
TI  - Rheumatic diseases in patients attending a clinic at a referral hospital in
      Yaounde, Cameroon.
AB  - BACKGROUND: The spectrum of rheumatic diseases in sub-Saharan Africa remains
      poorly defined. OBJECTIVES: To determine the spectrum of rheumatic diseases in
      Yaounde. DESIGN: Descriptive cross-sectional study. SETTING: Rheumatology clinic
      at the Yaounde General Hospital, Cameroon. SUBJECTS: Twelve thousand four hundred
      and ninety four patients were referred to the outpatient department of the
      Internal Medicine service of the General Hospital of Yaounde over a 12-month
      period. Of these cases, 536 (9.4%) were diagnosed as belonging to the general
      class of rheumatic conditions. There were 334 (62.31%) females and 202 (37.69%)
      males. The mean age was 52.72 +/- 5.3 years. RESULTS: The 536 cases were further
      classified as follows: degenerative disease of the spine 196 (36.5%),
      osteoarthritis of the limbs 110 (20.5%), regional musculo-skeletal disorders 83
      (15.5%), arthritis associated with infections 50 (9.3%), chronic inflammatory and
      connective tissue diseases 44 (8.2%), crystalline arthropathies 32 (5.9%) and
      miscellaneous (unclassified) rheumatic conditions 21 (4.1%). CONCLUSION: From
      these results, we concluded that degenerative disease of the spine and limbs are
      the most common forms of rheumatic disease in this region. Gout is the most
      commnon acute inflammatory arthropathy and rheumatoid arthritis the most
      prevalent arthropathy due to chronic inflammation.

PMID- 18074959
TI  - Psychosocial impact of sickle cell disease on mothers of affected children seen
      at University of Ilorin Teaching Hospital, Ilorin, Nigeria.
AB  - BACKGROUND: Attention paid to psychological disorders of mothers or families of
      children suffering from sickle cell disease (SCD) in Nigeria has been inadequate.
      OBJECTIVE: To assess the psychosocial impact of SCD on mothers of affected
      children and two control samples. DESIGN: A cross-sectional controlled study.
      SETTING: University of Ilorin Teaching Hospital, Ilorin, Nigeria. SUBJECTS: One
      hundred mothers of SCD affected children (SCD children) were the study sample
      while the controls were made of 75 mothers of children with bronchial asthma
      (asthmatics) and 75 mothers of children with some acute medical illness (AMI).
      RESULTS: The mothers of children with SCD (SCD mothers) were significantly likely
      to report burden in the areas of finance, time consumption and hindrance from
      enjoyment of live and were also more likely to over-protect their children. A
      total of 28% of SCD mothers were identified as probable cases with psychological
      problems on SRQ compared to 20% and 25% of mothers of asthmatics and AMI children
      respectively, this differences were, however, not statistically significant.
      CONCLUSION: As a result of the prevalent psychosocial impact of this disease on
      mothers it is strongly suggested that special consideration in terms of routine
      psychosocial assessment and treatment be incorporated into the various levels of
      health care system. There is also the need to encourage the establishment of more
      social organisations like SCD clubs where affected families can interact and
      counsel one another.

PMID- 18074960
TI  - Aetiology and presentation of HIV/AIDS-associated pulmonary infections in
      patients presenting for bronchoscopy at a referral hospital in northern Tanzania.
AB  - OBJECTIVES: To determine the aetiological agents of pulmonary infections in HIV
      infected Tanzanians and to correlate the causative agents with clinical,
      radiographic features, and mortality. DESIGN: A prospective study. SETTING:
      Kilimanjaro Christian Medical Centre (KCMC), Tanzania. SUBJECTS: Bronchoalveolar
      lavage fluid (BAL) were obtained from 120 HIV infected patients with pulmonary
      infections. BAL for causative agents was analysed and correlated with clinical
      and radiographic features, and one-month outcome. RESULTS: Causative agents were
      identified in 71 (59.2%) patients and in 16 of these patients, multiple agents
      were found. Common bacteria were identified in 35 (29.2%) patients, Mycobacterium
      tuberculosis in 28 (23.3%), Human Herpes Virus 8 (HHV8) in 12 (10%), Pneumocystis
      jiroveci in nine (7.5%) and fungi in five (4.2%) patients. Median CD4 T cell
      count of the patients with identified causes was 47 cells/microl (IQR 14-91) and
      in the 49 patients with undetermined aetiology was 100 cells/ microl (IQR 36-188;
      p = 0.01). Micronodular chest radiographic lesions were associated with presence
      of M. tuberculosis (p = 0.002). The one-month mortality was 20 (16.7%). The
      highest mortality was associated with HHV8 (41.7%) and M. tuberculosis (32.1%).
      Mortality in patients with undetermined aetiology was 11.3%. No death occurred in
      patients with PCP. CONCLUSION: In this population of severely immunosuppressed
      HIV-infected patients with pulmonary infection a variety of causative agents was
      identified. Micronodular radiographic lesions were indicative of TB. High
      mortality was associated with M. tuberculosis or HHV8. No death occurred in
      patients with P. jiroveci infection.

PMID- 18074961
TI  - Gastrointestinal perforation following blunt abdominal trauma.
AB  - OBJECTIVE: To highlight the pertinent management problems of bowel perforation
      following blunt abdominal trauma. DESIGN: A prospective descriptive study.
      SETTING: Hospital-based cohort over a nine year period in Jos University Teaching
      Hospital, Jos, Nigeria. SUBJECTS: A total of 23 patients with bowel perforation
      out of 8,970 trauma victims with a mean age of 28.5 years. INTERVENTION:
      Exploratory laparotomy, drainage of septic peritoneal fluid and wound saline
      lavage and closure of perforations were performed in all the 23 patients with
      clinical features and imaging signs suggestive of bowel perforation following
      blunt abdominal trauma. Femoral fractures were splinted and tube thoracostomy
      were carried out in four and two patients respectively. MAIN OUTCOME MEASURES:
      There is an apparent delay in presentation and diagnosis of traumatic bowel
      perforation following blunt abdominal trauma. Signs of peritoneal sepsis remain
      the most consistent findings in our environment. The morbidity and mortality
      following blunt abdominal trauma and bowel perforation are high because of
      established peritonitis. Delayed presentation or large leakage of bowel content
      into the peritoneal cavity and the attendant ease with which peritonitis develops
      in the latter are factors responsible. RESULTS: Delayed presentation (mean 3.05
      days) was observed in seven of 23 patients. Eight patients had concomitant
      injuries; two to the head, four had right femoral fracture and two blunt chest
      injury. Features of peritonitis were present at initial evaluation in 19
      patients. Seventeen patients were victims of motor vehicle accident. Radiological
      evidence of perforation (pneumoperitoneum) was present in only two of four
      patients with difficult diagnosis. Free peritoneal fluid without solid organ
      injury was detected in two patients with ultrasound. Diagnostic peritoneal lavage
      was, therefore, not used in any of our patients. The mean time from admission to
      laparotomy was six hours. Sites of perforations were: stomach (2), jejunum (9),
      ileum (8), jejunum/ileum (2) and colon (2). Sepsis originating from the
      perforated bowel was responsible for mortality in our patients who died in the
      perioperative period with concomitant injury playing significant role in three of
      11 patients with such injuries. CONCLUSION: Peritonitis following a bowel
      perforation after blunt abdominal trauma is often present at the time of
      presentation and diagnosis is usually made. In the few doubtful cases, often in
      patients presenting soon after trauma, X-ray and trans-abdominal ultrasonography
      will assist in making a diagnosis. Delayed presentation still accounts for a high
      mortality in bowel perforation following blunt abdominal trauma.

PMID- 18074962
TI  - Diagnosis, management and outcome of heart disease in Sudanese patients.
AB  - OBJECTIVES: To describe the diagnosis, management and outcome of patients with
      congenital heart disease seen at Sudan Heart Centre. DESIGN: A prospective follow
      up of all patients diagnosed as congenital heart disease. SETTING: Sudan Heart
      Centre. SUBJECTS: All children and adults with congenital heart disease seen at
      Sudan Heart Centre by one paediatric cardiologist from July 2004 to June 2005.
      RESULTS: Five hundred and twenty two patients were evaluated, 435 had abnormal
      hearts. The median age was 48 months (one day to sixty five years). Congenital
      heart disease constituted 87% and acquired heart disease and rhythm disorders
      13%. The frequency of the different cardiac heart disease was described and in
      general did not differ from that reported in the literature except for Ebstein
      anomaly which was noted to be four times more frequent than reported. Cardiac
      catheterisation was done for 81 patients, for diagnosis in 61 (75%) and for
      intervention in 20 (25%) patients. Balloon dilatation, atrial septostomy septal
      defect and patent ductus arteriosus closure with the help of a visiting team, the
      success rate for interventions was 95%. Surgery was done for 125 patients.
      Seventy three operations were done by the local team and 52 by the visiting team.
      The 30 day operative mortality was 8.3%. CONCLUSION: Paediatric cardiac service
      in Sudan in echocardiography and cardiac catheterisation is growing. Cardiac
      surgical results are comparable to the literature.

PMID- 18074963
TI  - Zinc for diarrhoea management in Sub-Saharan Africa: a review.
AB  - OBJECTIVES: To review the evidence supporting the inclusion of zinc for diarrhoea
      management specifically in sub-Saharan Africa where diarrhoea remains a leading
      cause of morbidity and mortality. DATA SOURCES: We searched PubMed for studies
      assessing the efficacy and effectiveness of zinc for the treatment and prevention
      of common childhood morbidities. STUDY SELECTION: We included only studies
      conducted in sub-Saharan Africa. DATA SYNTHESIS: Details of studies conducted in
      sub-Saharan Africa are presented in the context of the global evidence supporting
      the use of zinc for diarrhoea management. CONCLUSIONS: There is a significant
      body of evidence to support the use of zinc for diarrhoea management in sub
      Saharan Africa. The accelerated introduction of zinc into routine community-based
      diarrhoea treatment is critical for the reduction of diarrhoea morbidity and
      mortality.

PMID- 18074964
TI  - Body dysmorphic disorder: case report.
AB  - The desire for self-mutilation in the absence of any discernible psychopathology
      is relatively rare. Self-mutilation is most commonly a manifestation of an
      underlying psychopathology such as depression, schizophrenia, personality
      disorder, transexuality, body dysmorphic disorder and factitious disorder. In
      this article, a case in which a 29-year-old single Kenyan lady of African origin
      demanded a surgical operation to modify and reduce the size of her external
      genitalia is presented. Although female genital mutilation is still widespread in
      the country, this case is of interest in that the woman did not seek the usual
      circumcision but sought to specifically reduce the size of her labia minora so
      that she could feel like a normal woman. The unique challenges in her management
      are discussed. Possible aetiological factors in patients who demand surgical
      removal or modification of parts of their bodies without an obvious cause is
      discussed.

PMID- 18074965
TI  - Controlling the US health care system with policy wedges.
AB  - Two state-space models, one for the US health care system and one for the US
      economy, were developed and estimated for the period 1950-1999. The output from
      the US economy model was then used as a reference input to control the growth of
      the health care system model. The counterfactual history produced by simulating
      the controlled model shows that a reduction in investment and volume-based
      services would have been needed to bring the growth of the health care system in
      line with the US economy. Specifically, a 13% reduction in capital expenditure, a
      15% reduction in drug prices and a 32% reduction in prices for physician's
      services would have been needed over the late twentieth century. The methodology
      also suggests how universal health care programs might be designed using planning
      and economic incentives without either over-engineering plan provisions or using
      centralized, command-and-control approaches.

PMID- 18074966
TI  - Simulation tools for developing policies for complex systems: modeling the health
      and safety of refugee communities.
AB  - The U.S. Committee for Refugees and Immigrants estimated that there were over 33
      million refugees and internally displaced persons (IDPs) in the world at the
      beginning of 2005. IDP/Refugee communities behave in complex ways making it
      difficult to make policy decisions regarding the provision of humanitarian aid
      and health and safety. This paper reports the construction of an agent-based
      model that has been used to study humanitarian assistance policies executed by
      governments and NGOs that provide for the health and safety of refugee
      communities. Agent-based modeling (ABM) was chosen because the more widely used
      alternatives impose unrealistic restrictions and assumptions on the system being
      modeled and primarily apply to aggregate data. We created intelligent agents
      representing institutions, organizations, individuals, infrastructure, and
      governments and analyzed the resulting interactions and emergent behavior using a
      Central Composite Design of Experiments with five factors. The resulting model
      allows policy makers and analysts to create scenarios, to make rapid changes in
      parameters, and provides a test bed for concepts and strategies. Policies can be
      examined to see how refugee communities might respond to alternative courses of
      action and how these actions are likely to affect the health and well-being of
      the community.

PMID- 18074967
TI  - Contact tracing to control infectious disease: when enough is enough.
AB  - Contact tracing (also known as partner notification) is a primary means of
      controlling infectious diseases such as tuberculosis (TB), human immunodeficiency
      virus (HIV), and sexually transmitted diseases (STDs). However, little work has
      been done to determine the optimal level of investment in contact tracing. In
      this paper, we present a methodology for evaluating the appropriate level of
      investment in contact tracing. We develop and apply a simulation model of contact
      tracing and the spread of an infectious disease among a network of individuals in
      order to evaluate the cost and effectiveness of different levels of contact
      tracing. We show that contact tracing is likely to have diminishing returns to
      scale in investment: incremental investments in contact tracing yield diminishing
      reductions in disease prevalence. In conjunction with a cost-effectiveness
      threshold, we then determine the optimal amount that should be invested in
      contact tracing. We first assume that the only incremental disease control is
      contact tracing. We then extend the analysis to consider the optimal allocation
      of a budget between contact tracing and screening for exogenous infection, and
      between contact tracing and screening for endogenous infection. We discuss how a
      simulation model of this type, appropriately tailored, could be used as a policy
      tool for determining the appropriate level of investment in contact tracing for a
      specific disease in a specific population. We present an example application to
      contact tracing for chlamydia control.

PMID- 18074968
TI  - Evaluating hospital design from an operations management perspective.
AB  - This paper describes an evaluation method for the assessment of hospital building
      design from the viewpoint of operations management to assure that the building
      design supports the efficient and effective operating of care processes now and
      in the future. The different steps of the method are illustrated by a case study.
      In the case study an experimental design is applied to assess the effect of used
      logistical concepts, patient mix and technologies. The study shows that the
      evaluation method provides a valuable tool for the assessment of both
      functionality and the ability to meet future developments in operational control
      of a building design.

PMID- 18074969
TI  - Healthcare system design and parttime working doctors.
AB  - More doctors would like to work parttime. Since research on fitting healthcare
      system design with the structure of parttime jobs is lacking, we studied how
      parttime work for medical doctors could be enabled from a system design
      perspective. A theoretical analysis was performed, illustrated by two case
      studies. We conclude that introducing parttime work can provide the opportunity
      for improving system design and, therewith, performance. From the case studies it
      seems that work redesign can enable parttime work, and at the same time improve
      system performance. Better managing variability in the system contributed to
      this. The case studies results also showed that systems characterized by
      different levels of variability fit with different work contracts.

PMID- 18074971
TI  - Safe on arrival. Driving is a prime cause of U.S. occupational deaths. A virtual
      simulator intends to foster safer driving.

PMID- 18074970
TI  - A comprehensive simulation for wait time reduction and capacity planning applied
      in general surgery.
AB  - This paper describes the use of operational research techniques to analyze the
      wait list for the Division of General Surgery at the Capital District Health
      Authority in Halifax, Nova Scotia, Canada. A discrete event simulation model was
      developed to aid capacity planning decisions and to analyze the performance of
      the division. The analysis examined the consequences of redistributing beds
      between sites, and achieving standard patient lengths of stay, while contrasting
      them to current and additional resource options. From the results, multiple
      independent and combined options for stabilizing and decreasing waits for
      elective procedures were proposed.

PMID- 18074972
TI  - Leaders stay on their feet (and help others to, as well). Maintain your balance.

PMID- 18074973
TI  - Attributes of an injury-free culture, Part 4: Employee engagement.

PMID- 18074974
TI  - The ins and outs of voluntary respirator use.

PMID- 18074975
TI  - The NIOSH total inward leakage project.

PMID- 18074976
TI  - Entering unforgiving territory.

PMID- 18074977
TI  - Rescue requirements.

PMID- 18074978
TI  - How do you know your workers are qualified?

PMID- 18074979
TI  - Preventing dust explosions.

PMID- 18074980
TI  - Key to effective programs.

PMID- 18074981
TI  - Sterile emergency eyewash arrives.

PMID- 18074982
TI  - Employment-based retirement plan participation: geographic differences and
      trends, 2006.

PMID- 18074983
TI  - Be a sport (doc).

PMID- 18074984
TI  - A 4-month-old boy with an abdominal mass.

PMID- 18074985
TI  - Sports cardiology in the adolescent athlete: concerns for the pediatrician.

PMID- 18074986
TI  - Back pain in the adolescent athlete.

PMID- 18074987
TI  - Hip injuries in the adolescent athlete.

PMID- 18074988
TI  - The female adolescent athlete: specific concerns.

PMID- 18074989
TI  - The male adolescent athlete: specific concerns.

PMID- 18074990
TI  - Stress fractures in the adolescent athlete.
AB  - Consider stress fracture as a diagnosis in adolescent athletes complaining of
      worsening vague pain without a clear mechanism of injury. Remember that initial
      radiographs may be normal, especially early in the clinical course. If the
      fracture is of low risk for delayed or non-union, conservative management is
      indicated, with repeat radiographs 2 weeks after initiation of treatment. If a
      high-risk fracture is suspected, early diagnosis with MRI, bone scan, and, in
      some cases, CT is important for surgical decision making.

PMID- 18074991
TI  - Return-to-play decisions in the adolescent athlete: how to decide.

PMID- 18074992
TI  - Sports medicine and pediatric residency training: changing the paradigm.

PMID- 18074993
TI  - Trends in influenza vaccination in Canada, 1996/1997 to 2005.
AB  - OBJECTIVES: This article reports recent trends in influenza vaccination rates in
      Canada, provides data on predictors of vaccination in Canada for 2005, and
      examines longer-term effects of Ontario's universal influenza immunization
      program on vaccine uptake. DATA SOURCES: Data are from the 1996/1997 National
      Population Health Survey (NPHS) and the 2000/2001, 2003, and 2005 Canadian
      Community Health Survey (CCHS). ANALYTICAL TECHNIQUES: NPHS and CCHS data were
      used to estimate influenza vaccination rates of the population aged 12 or older.
      The Z test was used to assess differences between surveys, and the chi-squared
      test for trend was used to examine trends over time. Logistic regression was used
      to identify predictors of vaccination and to compare the odds of being vaccinated
      in Ontario versus other provinces. MAIN RESULTS: Nationally, influenza
      vaccination rates rose from 15% in 1996/1997 to 27% in 2000/2001, stabilized
      between 2000/2001 and 2003, and increased further to 34% by 2005. Vaccination
      rates for most high-risk groups still fall short of national targets. Ontarians
      continue to be more likely to be vaccinated than are residents of any other
      province, while residents of two of the territories--Nunavut and the Northwest
      Territories--are even more likely to be vaccinated than are Ontarians.

PMID- 18074994
TI  - Birth outcomes by neighbourhood income and recent immigration in Toronto.
AB  - OBJECTIVES: This article examines differences in birth outcomes by neighbourhood
      income and recent immigration for singleton live births in Toronto, Ontario. DATA
      SOURCES: The birth data were extracted from hospital discharge abstracts compiled
      by the Canadian Institute for Health Information. ANALYTICAL TECHNIQUES: A
      population-based cross-sectional study of 143,030 singleton live births to
      mothers residing in Toronto, Ontario from 1 April 1996 through 31 March 2001 was
      conducted. Neighbourhood income quintiles of births were constructed after
      ranking census tracts according to the proportion of their population below
      Statistics Canada's low-income cutoffs. Logistic regression was used to estimate
      odds ratios for the effects of neighbourhood income quintile and recent
      immigration on preterm birth, low birthweight and full-term low birthweight,
      adjusted for infant sex and maternal age. MAIN RESULTS: Low neighbourhood income
      was associated with a moderately higher risk of preterm birth, low birthweight,
      and full-term low birthweight. The neighbourhood income gradient was less
      pronounced among recent immigrants compared with longer-term residents. Recent
      immigration was associated with a lower risk of preterm birth, but a higher risk
      of low birthweight and full-term low birthweight.

PMID- 18074995
TI  - Work stress among health care providers.

PMID- 18074996
TI  - Hip fracture outcomes in the household population.

PMID- 18074997
TI  - Macroanatomy and microanatomy of the temporal lobe.
AB  - Because of its different functions and organization, the temporal lobe may be
      divided into lateral and medial parts. This separation may be useful for teaching
      purposes, since the medial temporal lobe needs a separated and a more precise
      study because of its complex structure and because it is the substrate where some
      specific types of epilepsy originate. The use of certain magnetic resonance
      imaging (MRI) sequences and protocols has improved the diagnosis of some
      particular epilepsies, but this technical benefit must be accompanied by the
      accurate knowledge of the anatomy of the temporal lobe. With this purpose we have
      prepared this article, which highlights the ultastructural and macroanatomy of
      the temporal lobe seen on MRI.

PMID- 18074998
TI  - Temporal lobe epilepsy: clinical semiology and neurophysiological studies.
AB  - Most partial epilepsy crises originate in the temporal lobe. Two main syndromes
      have been described in temporal lobe epilepsy (TLE): mesial temporal epilepsy and
      neocortical temporal epilepsy. In recent years, the number and types of drugs
      used to control the crises have significantly increased, but almost 30% of
      patients do not have complete control of their epilepsy. In those cases, surgery
      is an efficient therapeutic option, especially in the case of mesial temporal
      sclerosis. Before surgery, wide and complex neurophysiological studies are needed
      to precisely delineate the epileptogenic area. The clinical and
      neurophysiological aspects of TLE that may be useful for understanding this
      pathologic entity are reviewed.

PMID- 18074999
TI  - MR imaging of temporal lobe epilepsy.
AB  - In this article, we explore the expanding role of MRI in the diagnosis and
      management of patients with temporal lobe epilepsy. Both conventional and more
      advanced MRI techniques are capable of exploring a range of physiological
      phenomena not available in other imaging modalities, and thus provide valuable
      insight into the pathophysiology underlying temporal lobe epilepsy. These
      techniques alone and in concert are highly sensitive and specific in detecting
      epileptogenic lesions and identifying patients who would potentially benefit from
      surgical resection.

PMID- 18075000
TI  - Functional imaging in temporal lobe epilepsy.
AB  - This article highlights the importance of functional imaging methods in the
      diagnosis and preoperative planning in temporal lobe epilepsy TLE). It starts
      with a discussion of the role of ictal and interictal single-photon emission
      computed tomography (SPECT) and interictal positron emission tomography (PET) in
      lateralizing TLE. The next section discusses the role of blood oxygen level
      dependent (BOLD) functional magnetic resonance imaging (fMRI) and perfusion MRI,
      particularly for lateralization of language and memory in TLE patients. The final
      section explores the relatively new role that the emerging technique of diffusion
      tensor imaging (DTI) is playing in the evaluation of TLE.

PMID- 18075001
TI  - 3-Tesla MRI and temporal lobe epilepsy.
AB  - Magnetic resonance imagine (MRI) is the essential tool for the diagnosis and
      evaluation of epileptic patients due to the possibility of it identifying the
      epileptogenic substrate and the decisive value for the selection of surgical
      candidates in cases of refractory epilepsy. Because the main role of MRI in
      epilepsy relates to the detection of a structural injury, the quality of the
      image clearly determines the results. In structural studies, it can contribute to
      detecting small hippocampal alterations that may be missed with conventional
      techniques, and it is a more reliable tool for detecting small focal cortical
      dysplasias (FCD), which constitute the most frequent cause of dual injury. 3
      Tesla MRI also provides relevant information in functional studies. Its
      advantages rely on the rise in signal-to-noise ratio and its higher T2 contrast,
      and also, in the case of MR spectroscopy, on its higher chemical shift, which in
      general increases both the quality and the rapidity of acquisition. Finally,
      epilepsy is one of the main indications for obtaining cerebral activation maps,
      usually using the blood oxygen level dependent (BOLD) technique, which is one of
      the techniques that most benefits from the magnetic field increase.

PMID- 18075002
TI  - Sex differences in body fat parameters from the early reproductive to the
      postreproductive period of life: a multivariate analysis.
AB  - Sex diversity has been observed for many body parameters, and special attention
      has been paid to changes during puberty and menopause. In the present study we
      performed a multivariate analysis on several body fat parameters to obtain a
      synthetic overview of sex differences from the early reproductive period to the
      postreproductive period. The sample study is composed of 373 healthy Italian
      adults (294 females and 79 males). We have examined the amount of fat (in
      kilograms, as measured by dual-energy x-ray absorptiometry) in the left arm, left
      leg, left trunk hemisphere, right arm, right leg, and right trunk hemisphere,
      waist to hip ratio, and BMI. The sex differentiation from the early reproductive
      to the postreproductive period of life has been based on differences between the
      position of male and female centroids on the discriminant functions obtained for
      various periods of life. The difference between males and females increases
      suddenly after 20 years, reaching a maximum at 30 years. In the period between 30
      and 40 years the difference decreases quickly, and after 40 years the difference
      is relatively small and remains practically constant. The fact that maximum sex
      differentiation coincides with age of best reproductive efficiency points to a
      relationship between the body parameters investigated and hormone production
      related to human reproduction.

PMID- 18075003
TI  - Factors influencing prereproductive mortality in the isolated and preindustrial
      western Mediterranean population of La Alpujarra, 1900-1950.
AB  - We study the effects of several variables on the prereproductive mortality
      pattern in the isolated and rural population of La Alpujarra, located on the
      western Mediterranean coast (southeast Spain), in the first half of the 20th
      century. The study is a retrospective analysis from a total sample of 2,200
      deliveries, 2,085 of which were born alive and 171 of which did not survive to
      the 20th birthday. The potential influences of birthdate of children, twinning,
      firstborn, parental inbreeding, and sex on Alpujarran mortality were analyzed
      through logistic regression. Parity, family size, and birth interval effects were
      estimated through the difference between observed and expected mortality rates.
      In every case four age groups of mortality were considered because of the large
      influence of child growth: neonatal (less than 1 month of life), postneonatal
      infant (between 1 month and 1 year old), childhood (1-5 years old), and youth (5
      20 years old). The Alpujarran prereproductive mortality pattern can be summarized
      as the result of three main risk factors: biodemographic, biomechanical, and
      social and health determinants. In general, every factor showed a decreased
      effect as children grew. The most significant determinants were birthdate of
      children, which is more related to increased mother's awareness of child care
      than to health improvement, and family size associated with decreasing alimentary
      resources as the sibling number increased. Male mortality was higher than female
      mortality in children older than 1 year but not for infant mortality, possibly as
      a result of a reproductive behavior favorable to males. Although firstborn status
      and twinning appeared associated with high mortality, maternal age and birth
      interval were related to low risk, but these influences always ceased after the
      first month of life. Parental inbreeding did not show any effect on infant,
      childhood, or youth mortality.

PMID- 18075004
TI  - Prevalence and causes of chronic energy deficiency and obesity in Indian women.
AB  - We investigate the nutritional status of women in India and its relation to the
      prevalence of chronic energy deficiency (CED) and obesity. To do this, we have
      used the data from the Indian National Family Health Survey, 1998-1999, on body
      mass index (BMI) of ever-married women, ages 15-49 years, along with several
      socioeconomic factors, such as level of education, religion or caste,
      occupational status, and standard of living index. The study was based on 81,712
      women from 26 states and 6 zones, which were grouped according to geographic
      proximity of the states of India. A multiple linear regression analysis was done
      to see the relation between nutritional status of women and different
      socioeconomic factors. The data reveal that the prevalences of CED, overweight,
      and obesity in India are 31.2%, 9.4%, and 2.6%, respectively. The incidences of
      CED and obesity are negatively related. The prevalence of CED is the lowest in
      Arunachal Pradesh and highest in Orissa. Punjab has the highest prevalence of
      obesity, and Bihar has the lowest. For the zonewise distribution the Northeast
      zone has the lowest degree of prevalence of CED and the East zone is at the
      bottom of the list with the highest degree of malnutrition. We also found that
      the nutritional status of women goes together with the enhancement of their
      educational status, standard of living, and so on. There are also significant
      differences between rural and urban sectors and among castes, religions, and
      occupations. Furthermore, regression analysis shows that all the socioeconomic
      variables considered here significantly affect BMI in Indian women.

PMID- 18075005
TI  - Ancestral consanguinity and mortality among three endogamous populations of
      Chittoor District, Andhra Pradesh, India.
AB  - Consanguineous marriages have been practiced around the globe by many societies
      from time immemorial, particularly in South India. Consanguineous marriages play
      a major role in the health of a population, and diseases leading to mortality of
      the progeny are a consequence of detrimental recessive genes. To evaluate the
      effects of ancestral consanguinity on mortality in relation to consanguineous
      marriage, we have ascertained data from 1,500 women belonging to three endogamous
      communities (Akuthota Reddy, Odde, and Madiga) of Chittoor District, Andhra
      Pradesh, India. There were 500 women from each community. For each marriage we
      drew a family pedigree, extended upward to two earlier generations on either side
      of the spouses, to determine the prevalence and pattern of consanguinity, with
      detailed information on fertility and mortality. We observed a significant
      difference in the mortality rates between consanguineous and nonconsanguineous
      marriages when all the marriages of the women, women's parents, and (women's)
      husband's parents were considered in all three communities. In inbreeding, the
      offspring of earlier generations might have passed on deleterious genes to later
      generations (under unfavorable conditions), which resulted in a negative aspect
      of reproduction (among the offspring of the present couple).

PMID- 18075006
TI  - Genetic polymorphism of six DNA loci in six population groups of India.
AB  - The genetic profile based on autosomal markers, four microsatellite DNA markers
      (D8S315, FES, D8S592, and D2S1328) and two minisatellite DNA markers (TPMT and
      PDGFA), were analyzed in six endogamous populations to examine the effect of
      geographic and linguistic affiliation on the genetic affinities among the groups.
      The six populations are from three different states of India and are
      linguistically different. Marathas from western India speak Marathi, an Indo
      European language. Arayas, Muslims, Ezhavas, and Nairs from Kerala state of South
      India speak Malayalam, and Iyers from Tamil Nadu state speak Tamil. Genomic DNA
      was extracted from peripheral blood samples of random, normal, healthy
      individuals. Locus-specific PCR amplification was carried out, followed by
      electrophoresis of the amplicons and genotyping. All the loci were highly
      polymorphic and followed Hardy-Weinberg equilibrium, except for loci D8S315 and
      PDGFA in Iyers and Marathas, respectively. All six loci had high heterozygosity
      (average heterozygosity ranged from 0.73 to 0.76) and high polymorphism
      information content (0.57-0.90). The extent of gene differentiation among the six
      populations (G(ST) = 0.030) was greater than that for four Kerala populations
      (G(ST) = 0.011), suggesting proximity between the four Kerala populations. This
      result conforms with the cultural and linguistic background of the populations.
      The extent of diversity found among the populations probably resulted from the
      strict endogamous practices that they follow.

PMID- 18075007
TI  - N-acetyltransferase polymorphism among northern Sudanese.
AB  - Interindividual and interethnic differences in allele frequencies of N
      acetyltransferase (NAT2) single nucleotide polymorphisms (SNPs) are responsible
      for phenotypic variability of adverse drug reactions and susceptibility to
      cancer. We genotyped the seven NAT2 common SNPs in 127 randomly selected
      unrelated northern Sudanese subjects using allele-specific and RFLP polymerase
      chain reaction (PCR) based methods. Molecular genotyping was enough to designate
      alleles for 41 individuals unambiguously, whereas 63 individuals' alleles were
      inferred from haplotypes previously described. In the remaining 23 individuals,
      however, the phase of the SNPs could not be decided because of multiple SNP
      heterozygotes. Using computational methods in the HAP and Phase programs, we
      confirmed the inferred alleles of the 62 individuals and predicted the remaining
      23 ambiguous alleles. Twelve NAT2 alleles were identified. Four alleles coded for
      rapid acetylators (18%), and eight alleles coded for slow acetylators (82%). Two
      genotypes coded for rapid acetylation (3.9%), 10 for intermediate acetylation
      (27.6%), and 13 for slow acetylation (68.5%). The G191A African SNP and the G857A
      predominantly Asian SNP were each detected at a low frequency of 3.1%. The
      combination of molecular and computational analysis was useful in resolving
      ambiguous genotypes of NAT2 in multiple SNP heterozygotes. Among the northern
      Sudanese the SNPs associated with slow acetylation are more prevalent than in
      Caucasians and Asians. This and other African studies are suggestive of an
      African origin for NAT2-associated polymorphism.

PMID- 18075008
TI  - Sex-specific effect of the thermolabile C677T mutation in the
      methylenetetrahydrofolate reductase gene on angiographically assessed coronary
      artery disease in Brazilians.
AB  - Hyperhomocysteinemia is associated with increased coronary artery disease (CAD)
      risk. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the
      metabolism of homocysteine and presents a common mutation (C677T) that leads to a
      thermolabile enzyme, mild hyperhomocysteinemia, and increased CAD risk. The C677T
      MTHFR mutation was studied in 772 subjects (480 Caucasian Brazilians and 292
      African Brazilians) who underwent coronary angiography at the hemodynamic center
      of the Santa Izabel Hospital in Salvador, Bahia State, Brazil. The 677T allele
      frequency was increased in Caucasian Brazilians (28.1%) compared to the frequency
      observed in African Brazilians (18.3%; p < 0.001). In Caucasian Brazilians the
      frequency of the 677T homozygous genotype was increased in CAD cases (10.4%)
      compared to control subjects (1.4%; p = 0.014) in males but not in females. In
      African Brazilians the mutation was not associated with CAD in either sex. The
      multivariate logistic regression analysis of all the samples shows that the 677T
      homozygous interaction with sex was a significant CAD predictor, independent of
      other classical risk factors and ethnic group. The odds ratio associated with
      male 677T homozygotes was increased 9.2-fold (p = 0.021) compared to the 677C
      carriers. The present study suggests that the C677T MTHFR mutation is associated
      with increased CAD risk in a sex-dependent manner in Brazilians.

PMID- 18075009
TI  - Geographic structure in Gran Chaco Amerindians based on five X-chromosome STRs.
AB  - We investigated the genetic differentiation of five X-chromosome STR markers
      among five native South American Amerindian populations inhabiting three
      different areas of the Gran Chaco: Mocovi, Chorote, Wichi, Lengua, and Ayoreo.
      The observed genetic structure showed correspondence with geographic distribution
      more clearly than previous information obtained from autosomal STRs for the same
      samples. On the other hand, X-chromosome STR data did not agree with linguistic
      affinities. These markers proved to be informative for the study of the native
      populations of the Gran Chaco region.

PMID- 18075010
TI  - Next steps to reduce agricultural tractor overturn fatal and non-fatal injuries.

PMID- 18075011
TI  - Safety and health perceptions and concerns of custom harvesters.
AB  - This study elicited the perceptions and concerns of custom harvesters regarding
      safety and health issues faced in their operations, self-perceived knowledge of
      selected regulations, and self-perceived ability to train employees on the safe
      operation of equipment. The average age of custom harvesters' (CH) employees was
      22 to 25 years (47.2%). The most common length of the harvest season was 5 to 6
      months (70.9%). The most common responses to length of work day were 9 to 11
      hours (34.5%) and 12 to 14 hours (54.5%). In general, CH ranked combine operation
      experience as most important when hiring employees. The CH felt inexperience was
      the leading contributor to lost-time incidents. They were most concerned about
      DOT regulations and Worker's Compensation rules, but also felt they had a good
      knowledge of those areas.

PMID- 18075012
TI  - Airborne antibiotic concentrations in a swine feeding operation.
AB  - During the past 50 years, it has become common practice in the U.S. to add
      antibiotics to livestock feed to reduce disease and promote growth. Use of
      antibiotics in this manner has become the source of increasing controversy
      because overuse of antibiotics is suspected of leading to resistance in bacteria
      that cause human diseases. The purpose of this study was to measure airborne
      antibiotic concentrations in a swine production facility that routinely included
      antibiotics in feed. Samples were collected in a hog facility that included rooms
      devoted to farrowing, nursery, and growing operations. Analytical methods were
      developed to measure concentrations of the antibiotics tylosin and lincomycin in
      air samples. Tylosin was mixed in the feed in some of the rooms in the facility.
      While lincomycin was not added during this study, it had been used in this
      facility in the past and therefore was included in the analytical testing.
      Inhalable (n = 34), respirable (n = 37), and high-volume (n = 16) dust samples
      were collected on PVC filters over a two-month period. Tylosin concentrations
      were above the limit of quantification (LOQ) in 93% of the samples, while
      lincomycin concentrations were above the LOQ in only 9% of the samples (LOQ =
      0.04 ng/sample). The average tylosin concentrations were 3, 18, and 49 ng/m3 in
      the respirable, inhalable, and high-volume samples, respectively. No occupational
      or environmental worker exposure criteria currently exist for antibiotics in air.
      The results of this study may be used to estimate potential swine production
      worker exposures and to further study the association between these exposures and
      health effects.

PMID- 18075013
TI  - Noise exposures during potato processing and manufacture of animal feed.
AB  - A noise exposure survey was conducted at an agricultural facility to evaluate
      noise exposures during potato processing and during the manufacture of alfalfa
      pellets. Of the 19 employees monitored, five reached or exceeded the National
      Institute for Occupational Safety and Health recommended exposure limit for
      occupational noise. Four of these employees were from the potato processing area,
      and one was from the alfalfa pellet-mill operation. Two of the five (bagger and
      pellet-mill operator) also exceeded the Occupational Safety and Health
      Administration action level. The facility has a well-managed hearing conservation
      program for employees in the potato processing area, but not in the alfalfa
      manufacturing area.

PMID- 18075014
TI  - Interventions to reduce low-back injury risk among youth who perform feed
      handling and scooping tasks on farms.
AB  - Children and adolescents who perform farm chores are exposed to cumulative trauma
      injury risks, particularly to the low back. For example, they may routinely
      handle heavy materials and need to adopt awkward postures during farm chores. Two
      potential interventions aimed at reducing low-back injury risk were examined in
      the laboratory: the use of a rugged cart and proper orienting of feed bags to
      ease feed transport; and the use of a modified feed bin, intended to allow easier
      access to product scooped from the bin at different levels. A lumbar motion
      monitor device was used to quantify trunk movement and determine injury risk
      level. Fourteen male and female youth who regularly perform these farm chores
      participated in the study. The cart significantly reduced low-back injury risk by
      nearly 10%, compared with manual feed bag lifting and carrying. The modified feed
      bin did not significantly reduce low-back injury risk, compared with traditional
      scooping. Regardless of the method used, however, scooping feed from the top of
      the bin reduced lower back disorder risk by 50% or more compared to the two lower
      levels. This study showed that relatively simple and low-cost solutions can be
      applied to farm environments to help protect the low backs of youth who perform
      farm chores.

PMID- 18075015
TI  - Safety performance of animal confinement floors: slip, trip, and fall injuries in
      Finland.
AB  - Slip, trip, and fall (STF) injuries are common in agriculture. The aims of this
      study were to characterize STF injuries and to identify floor-related safety
      problems that can be reduced or eliminated through building design. Our material
      consisted of Finnish agricultural injury claim records for the period 1992-2002.
      The material included 6,414 slip, trip, and fall injuries that occurred in dairy,
      beef and swine production and were caused by floor structures. We examined coded
      information and injury descriptions to identify causes and contributing factors.
      The performance approach (PA) was used as a framework for discussing findings and
      their application to building design. PA provides a logic model for building
      design that considers the needs of workers, animals, and production processes.
      Nearly half (42%) of agricultural injuries occurred in dairy, beef, and swine
      production work. Fourteen percent of these injuries were slips, trips, and falls
      (STF) related to floor structures. More than 450 work years were lost due to
      disability resulting from these injuries. Many STF injuries occurred in milking
      (n = 1135), moving feeds (n = 962), and animal transport and care (n = 880). More
      than half (59%) of STF injuries occurred while carrying or moving a load. STF
      injury causes included floors, door sills, gutters, curbs, steps, ramps, grates,
      and contaminants like water, ice, snow, manure, detergent, forage, and hay. Men
      had a lower STF injury risk compared to women (RR = 0.63, 95% CI: 0.61-0.67). The
      magnitude and nature of STF injuries suggest that there is a need for improving
      the safety performance of floors and related structures. Key areas include slip
      resistant floorings, effective contamination control, macro structures
      (elevations, entrances, access ways), and logistics for materials handling and
      storage spaces.

PMID- 18075016
TI  - Diagnosed skin diseases among migrant farmworkers in North Carolina: prevalence
      and risk factors.
AB  - Skin diseases are common among farmworkers, yet little research documents their
      prevalence and risk factors. This analysis documents the prevalence of skin
      diseases among farmworkers in North Carolina, examines variation in the
      prevalence across the agricultural season, and delineates factors associated with
      skin disease. Data are from a longitudinal surveillance study with assessments at
      approximately three-week intervals from May through October 2005. The sample
      included 304 farmworkers from 45 camps with 1048 data points. Data collection
      included a structured interview and a standard set often digital photographs. A
      board-certified dermatologist reviewed the photographs and made specific
      diagnoses in five categories: inflammatory disease, infection, pigmentary
      disorder, tumor, and trauma. The prevalences of the five skin disease categories
      and specific diagnoses are described with counts and frequencies for the entire
      season and for six time periods. The inflammatory disease and infectious disease
      categories are modeled with an extension of logistic regression that accounts for
      repeated measures and clustering of farmworkers within camps. Farmworkers
      experience high levels of inflammatory skin disease (57.2%) including acne,
      folliculitis, and contact dermatitis; infectious skin disease (73.8%) including
      tinea pedis, onychomycosis, and warts; pigmentary disorders (19.1%); and trauma
      (34.5%). The odds of inflammatory skin disease decreased with age, while those
      for infectious skin disease increased with age. The odds of inflammatory skin
      disease increased with pesticide exposure and decreasing housing quality. Skin
      diseases are highly prevalent among farmworkers. Research is needed to delineate
      specific factors causing high levels of infection and inflammation in this
      population.

PMID- 18075017
TI  - Pay gambit is transparent.

PMID- 18075018
TI  - Pay review evidence sparks debate about whether money is a motivator.

PMID- 18075019
TI  - Save your prayers.
AB  - The ability to be a caring, compassionate nurse is inherent and not the
      prerogative of those with religious beliefs, says Sally Gooch. Respect for
      religious beliefs is different from a moral duty not to discriminate.

PMID- 18075020
TI  - Do-it-yourself delivery.
AB  - More women are opting for an unassisted 'freebirth'. But midwives and doctors are
      concerned about the dangers.

PMID- 18075021
TI  - Verification of expected death.
AB  - This article describes the procedure for the verification of an expected death,
      as it relates to nursing staff.

PMID- 18075022
TI  - Infection risks associated with needleless intravenous access devices.
AB  - Needleless intravenous (i.v.) access devices were initially introduced into
      clinical practice to reduce the rate of i.v. catheter-related needlestick
      injuries. Their efficacy for this purpose has been confirmed in subsequent
      reports. However, since their introduction approximately 15 years ago there have
      been conflicting reports about the risk of i.v. catheter-related bloodstream
      infection. This article reviews the risk of catheter-related bloodstream
      infection associated with needleless i.v. access devices and outlines the types
      of needleless i.v. access devices available.

PMID- 18075023
TI  - Midline catheters: indications, complications and maintenance.
AB  - Midline catheters are commonly inserted by nurses to make short and long-term
      infusion of intravenous fluids and medication easier. This article provides an
      overview of the value of these devices in adult nursing. It also describes the
      history and management of the midline catheter in relation to current research
      and evidence-based practice.

PMID- 18075024
TI  - Patient dignity.

PMID- 18075025
TI  - The art of empathy.

PMID- 18075026
TI  - International record.

PMID- 18075027
TI  - Accurate and robust reconstruction of a surface model of the proximal femur from
      sparse-point data and a dense-point distribution model for surgical navigation.
AB  - Constructing a 3-D surface model from sparse-point data is a nontrivial task.
      Here, we report an accurate and robust approach for reconstructing a surface
      model of the proximal femur from sparse-point data and a dense-point distribution
      model (DPDM). The problem is formulated as a three-stage optimal estimation
      process. The first stage, affine registration, is to iteratively estimate a scale
      and a rigid transformation between the mean surface model of the DPDM and the
      sparse input points. The estimation results of the first stage are used to
      establish point correspondences for the second stage, statistical instantiation,
      which stably instantiates a surface model from the DPDM using a statistical
      approach. This surface model is then fed to the third stage, kernel-based
      deformation, which further refines the surface model. Handling outliers is
      achieved by consistently employing the least trimmed squares (LTS) approach with
      a roughly estimated outlier rate in all three stages. If an optimal value of the
      outlier rate is preferred, we propose a hypothesis testing procedure to
      automatically estimate it. We present here our validations using four
      experiments, which include 1) leave-one-out experiment, 2) experiment on
      evaluating the present approach for handling pathology, 3) experiment on
      evaluating the present approach for handling outliers, and 4) experiment on
      reconstructing surface models of seven dry cadaver femurs using clinically
      relevant data without noise and with noise added. Our validation results
      demonstrate the robust performance of the present approach in handling outliers,
      pathology, and noise. An average 95-percentile error of 1.7-2.3 mm was found when
      the present approach was used to reconstruct surface models of the cadaver femurs
      from sparse-point data with noise added.

PMID- 18075028
TI  - A novel fuzzy pain demand index derived from patient-controlled analgesia for
      postoperative pain.
AB  - A multilayer hierarchical structure for an intelligent analysis system is
      described in this paper. Four levels (patients', measurement, Web-based, and
      interpreting) are used to collect massive amounts from clinical information and
      analyze it with both traditional and artificial intelligent methods. To support
      this, a novel fuzzy pain demand (FPD) index derived from the interval of each
      bolus of patient-controlled analgesia (PCA) is designed and documented in a large
      scale clinical survey. The FPD index is modeled according to a fuzzy modeling
      algorithm to interpret the self-titration of the drug delivery. A total of 255
      patients receiving intravenous PCA using morphine (1 mg/ml) tested this index by
      offline analysis from this system. We found the FPD index modeled from a fuzzy
      modeling algorithm to interpret the self-titration of the drug delivery can show
      the patients' dynamic demand and past efforts to overcome the postoperative pain.
      Moreover, it could become an online system to monitor patients' demand or intent
      to treat their pain so these factors could be entered into a patient's chart
      along with temperature, blood pressure, pulse, and respiration rates when medical
      practitioners check the patients.

PMID- 18075029
TI  - Markov model assessment of subjects' clinical skill using the E-Pelvis physical
      simulator.
AB  - Inherent difficulties evaluating clinical competence of physicians has led to the
      widespread use of subjective skill assessment techniques. Inspired by an analogy
      between spoken language and surgical procedure, a generalized methodology using
      Markov models (MMs), independent of the modality under study, was developed. The
      methodology applied to an endoscopic experiment in "Generalized approach for
      modeling minimally invasive surgery as a stochastic process using a discrete
      Markov model" by J. Rosen et al. (IEEE Trans. Biomed. Eng., Vol. 53, No. 3, pp.
      399-413, Mar. 2006) is modified and applied to data collected with the E-Pelvis
      physical simulator. The simulator incorporates five contact pressure sensors
      located in key anatomical landmarks. Two 32-state fully connected MMs are used,
      one for each skill level. Each state corresponds to a unique five-dimensional
      signature of contact pressures. Statistical distances measured between models
      representing subjects with different skill levels are sensitive enough to provide
      an objective measure of medical skill level. The method was tested with 41 expert
      subjects and 41 novice subjects in addition to the 30 subjects used for training
      the MM. Of the 82 subjects, 76 (92%) were classified correctly. Unique state
      transitions as well as pressure magnitudes for corresponding states were found to
      be skill dependent. The "white box" nature of the model provides insight into the
      examination process performed.

PMID- 18075030
TI  - Time-varying causal coherence function and its application to renal blood
      pressure and blood flow data.
AB  - This paper describes the development of a model-based approach to estimating both
      feedforward and feedback paths of causal time-varying coherence functions (TVCF).
      Theoretical derivations of the coherence bounds of the causal TVCF using the
      proposed approach are also provided. Both theoretical derivations and simulation
      results revealed interesting observations, and they were corroborated using
      experimental renal blood pressure and flow data. Specifically, both theoretical
      derivations and experimental data showed that in certain cases, the calculation
      of the traditional TVCF was inappropriate when the system under investigation was
      a causal system. Moreover, the use of the causal TVCF not only provides
      quantitative assessment of the coupling between the two signals, but it also
      provides valuable insights into the composition of the physical structure of the
      renal autoregulatory system.

PMID- 18075031
TI  - Gaussian process modeling of EEG for the detection of neonatal seizures.
AB  - Gaussian process (GP) probabilistic models have attractive advantages over
      parametric and neural network modeling approaches. They have a small number of
      tuneable parameters, can be trained on relatively small training sets, and
      provide a measure of prediction certainty. In this paper, these properties are
      exploited to develop two methods of highlighting the presence of neonatal
      seizures from electroencephalograph (EEG) signals. In the first method, the
      certainty of the GP model prediction is used to indicate the presence of
      seizures. In the second approach, the hyperparameters of the GP model are used.
      Tests are carried out with a feature set of ten EEG measures developed from
      various signal processing techniques. Features are evaluated using a neural
      network classifier on 51 h of real neonatal EEG. The GP measures, in particular,
      the prediction certainty approach, produce a high level of performance compared
      to other modeling methods and methods currently in clinical use for EEG analysis,
      indicating that they are an important and useful tool for the real-time detection
      of neonatal seizures.

PMID- 18075032
TI  - A genetic algorithm for the resolution of superimposed motor unit action
      potentials.
AB  - This paper presents a novel method, which aims at resolving difficult
      superimpositions of motor unit action potentials (MUAPs) obtained from single
      channel intramuscular electromyographic recordings. Resolution is achieved by
      means of a genetic algorithm (GA) combined with a gradient descent method. This
      dual optimization scheme has been tested by means of simulations of isolated
      superimpositions involving two to six MUAPs, along with simulated extended
      signals of 10-s duration where the density reached 300 MUAPs/s. Of the hundreds
      of isolated superimpositions tested, more than 90% of the MUAPs were positively
      identified. With extended signals, identification rates of better than 85% were
      obtained. The GA alone accounted for up to an 8% improvement over the
      decomposition conducted using only template matching.

PMID- 18075033
TI  - A nonlinear Bayesian filtering framework for ECG denoising.
AB  - In this paper, a nonlinear Bayesian filtering framework is proposed for the
      filtering of single channel noisy electrocardiogram (ECG) recordings. The
      necessary dynamic models of the ECG are based on a modified nonlinear dynamic
      model, previously suggested for the generation of a highly realistic synthetic
      ECG. A modified version of this model is used in several Bayesian filters,
      including the Extended Kalman Filter, Extended Kalman Smoother, and Unscented
      Kalman Filter. An automatic parameter selection method is also introduced, to
      facilitate the adaptation of the model parameters to a vast variety of ECGs. This
      approach is evaluated on several normal ECGs, by artificially adding white and
      colored Gaussian noises to visually inspected clean ECG recordings, and studying
      the SNR and morphology of the filter outputs. The results of the study
      demonstrate superior results compared with conventional ECG denoising approaches
      such as bandpass filtering, adaptive filtering, and wavelet denoising, over a
      wide range of ECG SNRs. The method is also successfully evaluated on real
      nonstationary muscle artifact. This method may therefore serve as an effective
      framework for the model-based filtering of noisy ECG recordings.

PMID- 18075034
TI  - Compression of biomedical signals with mother wavelet optimization and best-basis
      wavelet packet selection.
AB  - We propose a novel scheme for signal compression based on the discrete wavelet
      packet transform (DWPT) decompositon. The mother wavelet and the basis of wavelet
      packets were optimized and the wavelet coefficients were encoded with a modified
      version of the embedded zerotree algorithm. This signal dependant compression
      scheme was designed by a two-step process. The first (internal optimization) was
      the best basis selection that was performed for a given mother wavelet. For this
      purpose, three additive cost functions were applied and compared. The second
      (external optimization) was the selection of the mother wavelet based on the
      minimal distortion of the decoded signal given a fixed compression ratio. The
      mother wavelet was parameterized in the multiresolution analysis framework by the
      scaling filter, which is sufficient to define the entire decomposition in the
      orthogonal case. The method was tested on two sets of ten electromyographic (EMG)
      and ten electrocardiographic (ECG) signals that were compressed with compression
      ratios in the range of 50%-90%. For 90% compression ratio of EMG (ECG) signals,
      the percent residual difference after compression decreased from (mean +/- SD)
      48.6 +/- 9.9% (21.5 +/- 8.4%) with discrete wavelet transform (DWT) using the
      wavelet leading to poorest performance to 28.4 +/- 3.0% (6.7 +/- 1.9%) with DWPT,
      with optimal basis selection and wavelet optimization. In conclusion, best basis
      selection and optimization of the mother wavelet through parameterization led to
      substantial improvement of performance in signal compression with respect to DWT
      and randon selection of the mother wavelet. The method provides an adaptive
      approach for optimal signal representation for compression and can thus be
      applied to any type of biomedical signal.

PMID- 18075035
TI  - Expediting the identification of impaired channels in cochlear implants via
      analysis of speech-based confusion matrices.
AB  - There is significant variability in the benefit provided by cochlear implants to
      severely deafened individuals. The reasons why some subjects exhibit low speech
      recognition scores are unknown; however, underlying physiological or
      psychophysical factors may be involved. Certain phenomena, such as
      indiscriminable electrodes and nonmonotonic pitch rankings, might hint at
      limitations in the ability of individual channels in the cochlear implant and/or
      sensorineural pathway to convey speech information. In this paper, four
      approaches for analyzing the results of a simple listening test using speech
      stimuli are investigated for the purpose of targeting channels of concern in
      order for follow-on psychophysical experiments to correctly identify channels
      performing in an "impaired" or anomalous manner. Listening tests were first
      conducted with normal-hearing subjects and acoustic models simulating channel
      specific anomalies. Results indicate that these proposed analyses perform
      significantly better than chance in providing information about the location of
      anomalous channels. Vowel and consonant confusion matrices from six cochlear
      implant subjects were also analyzed to test the robustness of the proposed
      analyses to variability intrinsic to cochlear implant data. The current study
      suggests that confusion matrix analyses have the potential to expedite the
      identification of impaired channels by providing preliminary information prior to
      exhaustive psychophysical testing.

PMID- 18075036
TI  - System identification from multiple short-time-duration signals.
AB  - System identification problems often arise where the only modeling records
      available consist of multiple short-time-duration signals. This motivates the
      development of a modeling approach that is tailored for this situation. An
      identification algorithm is presented here for parameter estimation based on
      minimizing the simulated prediction error, across multiple signals. The
      additional complexity of estimating the initial states corresponding to each
      signal is removed from the estimation algorithm. A numerical simulation
      demonstrates that the proposed algorithm performs well in comparison to the often
      used least squares method (which leads to biased estimates when identifying
      systems from measurement noise corrupted signals). The approach is applied to the
      identification of the passive oculomotor plant; parameters are estimated that
      describe the dynamics of the plant, which represent the time constants of the
      visco-elastic elements that characterize the plant connective tissue.

PMID- 18075037
TI  - Establishing causality with whitened cross-correlation analysis.
AB  - In many biomedical applications, it is important to determine whether two
      recorded signals have a causal relationship and, if so, what the nature of that
      relationship is. Many advanced techniques have been proposed to characterize this
      relationship, but in practice simple techniques such as cross-correlation
      analysis are used. Unfortunately, the traditional cross-correlation analysis is
      influenced by the autocorrelation of the signals as much as it is by the
      relationship between the signals. Practically, this results in the cross
      correlation suggesting that the signals are correlated over a broad range of
      lags. Prewhitening the signals overcomes this limitation and reveals the
      essentially causal relationship between the signals. This is a simple method that
      can also easily generalize cross-correlation analysis to nonstationary signals,
      which are frequently encountered in biomedical applications. This technique has
      been used in other fields, but remains mostly undiscovered in biomedical
      research. In the case of a purely causal relationship, we show that whitened
      cross-correlation analysis is equivalent to directly estimating the all-pass
      component of the transfer function that relates the signals. We give examples of
      this type of analysis applied to several biomedical applications to demonstrate
      some of the new insights and information that can be produced by this type of
      analysis.

PMID- 18075038
TI  - Assessment of blood coagulation under various flow conditions with ultrasound
      backscattering.
AB  - Several in vitro studies have employed ultrasonic techniques to detect varying
      properties of coagulating blood under static or stirred conditions. Most of those
      studies mainly addressed on the development and feasibility of modalities and
      however were not fully considering the effect of blood flow. To better elucidate
      this issue, ultrasonic backscattering were measured from the coagulating porcine
      blood circulated in a mock flow loop with various steady laminar flows at mean
      shear rates from 10 to 100 s(-1). A 3 ml of 0.5 M CaCl2 solution for inducing
      blood coagulation was added to that of 30 ml blood circulated in the conduit. For
      each measurement carried out with a 10-MHz transducer, backscattered signals
      digitized at 100-MHz sampling frequency were acquired for a total of 20 min at
      temporal resolution of 50 A-lines per s. The integrated backscatter (IB) was
      calculated for assessing backscattering properties of coagulating blood. The
      results show that blood coagulation tended to be increased corresponding to the
      addition of CaCl2 solution: the IB was increased approximately 6.1 +/- 0.6 (mean
      +/- standard deviation), 5.4 +/- 0.9, and 4.5 +/- 1.2 dB at 310 +/- 62, 420 +/-
      88, and 610 +/- 102 s associated with mean shear rates of 10, 40, and 100 s(-1),
      respectively. The rate of increasing IB for evaluating the growth of clot was
      estimated to be 0.075 +/- 0.017, 0.052 +/- 0.027, and 0.038 +/- 0.012 delta dB
      delta s(-1) corresponding to the increase of mean shear rates. These results
      consistently demonstrate that higher shear rate tends to prolong the duration for
      the flowing blood to be coagulated and to decrease the rate of IB. Moreover, the
      laminar flow was changed to turbulent flow during that the blood was clotting
      discerned by spatial variations of ultrasound backscattering in the conduit. All
      these results validate that ultrasound backscattering is feasible to be utilized
      for detecting and assessing blood coagulation under dynamic conditions.

PMID- 18075039
TI  - Ingestible capsule for impedance and pH monitoring in the esophagus.
AB  - Twenty-four-hour ambulatory pH monitoring is an essential tool for diagnosing
      gastroesophageal reflux disease (GERD). Simultaneous impedance and pH monitoring
      of the esophagus improves the detection and characterization of GERD.
      Conventional catheter-based monitoring systems are uncomfortable and interfere
      with the normal activity of the patient. To overcome these disadvantages,
      different wireless esophageal monitoring systems have been proposed. A capsule
      containing sensors for impedance and pH monitoring with wireless communication
      capabilities is presented. A low cost miniature microcontroller was utilized for
      interfacing between the sensors and a wireless transmitter. The microcontroller
      program allowed efficient management of the electric power provided by a 3-V
      battery. Magnetic holding is proposed as an alternative to surgical affixation of
      the monitoring capsule. Permanent neodymium magnets separated by 27 cm
      successfully held the capsule in a test tube. Experimental results demonstrated
      that friction force can aid magnetic holding to overcome peristalsis. The
      proposed design efficiently detected acid and nonacid reflux. More research
      regarding the holding method and capsule packaging are necessary to optimize the
      mechanical performance of the proposed design in order to facilitate clinical
      testing on human subjects.

PMID- 18075040
TI  - Impedance-based ventilation detection during cardiopulmonary resuscitation.
AB  - It has been suggested to develop automated external defibrillators with the
      ability to monitor cardiopulmonary resuscitation (CPR) performance online and
      give corrective feedback in order to improve the resuscitation quality. Thoracic
      impedance changes are closely correlated to lung volume changes and can be used
      to monitor the ventilatory activity. We developed a pattern-recognition-based
      detection system that uses thoracic impedance to accurately detect ventilation
      during ongoing CPR. The detection system was developed and evaluated on
      recordings of real-world resuscitation efforts of cardiac arrest patients where
      ventilations were manually annotated by human experts. The annotated ventilations
      were detected with an overall positive predictive value of 95.5% for a
      sensitivity of 90.4%. During chest compressions, the detection system achieved a
      mean positive predictive value of 94.8% for a sensitivity of 88.7%. The results
      suggest that accurate ventilation detection during CPR based on the proposed
      approach is feasible, and that the performance is not significantly degraded in
      the presence of chest compressions.

PMID- 18075041
TI  - Novel eye gaze tracking techniques under natural head movement.
AB  - Most available remote eye gaze trackers have two characteristics that hinder them
      being widely used as the important computer input devices for human computer
      interaction. First, they have to be calibrated for each user individually;
      second, they have low tolerance for head movement and require the users to hold
      their heads unnaturally still. In this paper, by exploiting the eye anatomy, we
      propose two novel solutions to allow natural head movement and minimize the
      calibration procedure to only one time for a new individual. The first technique
      is proposed to estimate the 3-D eye gaze directly. In this technique, the cornea
      of the eyeball is modeled as a convex mirror. Via the properties of convex
      mirror, a simple method is proposed to estimate the 3-D optic axis of the eye.
      The visual axis, which is the true 3-D gaze direction of the user, can be
      determined subsequently after knowing the angle deviation between the visual axis
      and optic axis by a simple calibration procedure. Therefore, the gaze point on an
      object in the scene can be obtained by simply intersecting the estimated 3-D gaze
      direction with the object. Different from the first technique, our second
      technique does not need to estimate the 3-D eye gaze directly, and the gaze point
      on an object is estimated from a gaze mapping function implicitly. In addition, a
      dynamic computational head compensation model is developed to automatically
      update the gaze mapping function whenever the head moves. Hence, the eye gaze can
      be estimated under natural head movement. Furthermore, it minimizes the
      calibration procedure to only one time for a new individual. The advantage of the
      proposed techniques over the current state of the art eye gaze trackers is that
      it can estimate the eye gaze of the user accurately under natural head movement,
      without need to perform the gaze calibration every time before using it. Our
      proposed methods will improve the usability of the eye gaze tracking technology,
      and we believe that it represents an important step for the eye tracker to be
      accepted as a natural computer input device.

PMID- 18075042
TI  - Tissue damage by pulsed electrical stimulation.
AB  - Repeated pulsed electrical stimulation is used in a multitude of neural
      interfaces; damage resulting from such stimulation was studied as a function of
      pulse duration, electrode size, and number of pulses using a fluorescent assay on
      chick chorioallontoic membrane (CAM) in vivo and chick retina in vitro. Data from
      the chick model were verified by repeating some measurements on porcine retina in
      vitro. The electrode size varied from 100 microm to 1 mm, pulse duration from 6
      micros to 6 ms, and the number of pulses from 1 to 7500. The threshold current
      density for damage was independent of electrode size for diameters greater than
      300 microm, and scaled as 1/r2 for electrodes smaller than 200 microm. Damage
      threshold decreased with the number of pulses, dropping by a factor of 14 on the
      CAM and 7 on the retina as the number of pulses increased from 1 to 50, and
      remained constant for a higher numbers of pulses. The damage threshold current
      density on large electrodes scaled with pulse duration as approximately 1/t0.5,
      characteristic of electroporation. The threshold current density for repeated
      exposure on the retina varied between 0.061 A/cm2 at 6 ms to 1.3 A/cm2 at 6
      micros. The highest ratio of the damage threshold to the stimulation threshold in
      retinal ganglion cells occurred at pulse durations near chronaxie-around 1.3 ms.

PMID- 18075043
TI  - Predicting arterial stiffness from the digital volume pulse waveform.
AB  - Cardiovascular disease (CVD) is currently the biggest single cause of mortality
      in the developed world, hence, the early detection of its onset is vital for
      effective prevention therapies. Aortic stiffness as measured by aortic pulse wave
      velocity (PWV) has been shown to be an independent predictor of CVD, however, the
      measurement of PWV is complex and time consuming. Recent studies have shown that
      pulse contour characteristics depend on arterial properties such as arterial
      stiffness. This paper presents a method for estimating PWV from the digital
      volume pulse (DVP), a waveform that can be rapidly and simply acquired by
      measuring the transmission of infra-red light through the finger pulp. PWV and
      DVP were measured on 461 subjects attending a clinic in South East London.
      Techniques for extracting features from the DVP contour based on physiology and
      information theory were compared. Low and high stiffness were defined according
      to a threshold level of PWV chosen to be 10 m/s. Using a support vector machine
      based classifier, it is possible to achieve high overall classification rates on
      unseen data. Further, the use of support vector regression techniques lead to a
      direct real-valued estimate of PWV which outperforms previous methods based on
      multilinear regression. We, therefore, conclude that support vector machine-based
      classification and regression techniques provide effective prediction of arterial
      stiffness from the simple measurement of the digital volume pulse. This technique
      could be usefully employed as a cheap and effective CVD screening technique for
      use in general practice clinics.

PMID- 18075044
TI  - An electromechanical swing-phase-controlled prosthetic knee joint for conversion
      of physiological energy to electrical energy: feasibility study.
AB  - Microprocessor-controlled prostheses facilitate a more natural and efficient gait
      for individuals with above-knee amputations by continually adjusting the level of
      swing-phase damping. One caveat associated with these technologies is that the
      user must charge the onboard batteries on a daily basis. It is, therefore, the
      aim of this study to examine the feasibility of using an electromechanical system
      to provide prosthetic swing-phase damping and, concomitantly, the function of
      converting physiological energy that is normally dissipated during the swing
      phase, to electrical energy. Gait data from a single subject and data from a
      kinematic simulator were used to develop an empirical model. The findings in this
      study indicate that an electromagnetic system has appropriate characteristics for
      use in swing-phase control and also has the potential to recover energy under
      particular conditions.

PMID- 18075045
TI  - Use of induced acceleration to quantify the (de)stabilization effect of external
      and internal forces on postural responses.
AB  - Due to the mechanical coupling between the body segments, it is impossible to see
      with the naked eye the causes of body movements and understand the interaction
      between movements of different body parts. The goal of this paper is to
      investigate the use of induced acceleration analysis to reveal the causes of body
      movements. We derive the analytical equations to calculate induced accelerations
      and evaluate its potential to study human postural responses to support-surface
      translations. We measured the kinematic and kinetic responses of a subject to
      sudden forward and backward translations of a moving platform. The kinematic and
      kinetics served as input to the induced acceleration analyses. The induced
      accelerations showed explicitly that the platform acceleration and deceleration
      contributed to the destabilization and restabilization of standing balance,
      respectively. Furthermore, the joint torques, coriolis and centrifugal forces
      caused by swinging of the arms, contributed positively to stabilization of the
      Center of Mass. It is concluded that induced acceleration analyses is a valuable
      tool in understanding balance responses to different kinds of perturbations and
      may help to identify the causes of movement in different pathologies.

PMID- 18075046
TI  - Ambulatory monitoring of physical activities in patients with Parkinson's
      disease.
AB  - A new ambulatory method of monitoring physical activities in Parkinson's disease
      (PD) patients is proposed based on a portable data-logger with three body-fixed
      inertial sensors. A group of ten PD patients treated with subthalamic nucleus
      deep brain stimulation (STN-DBS) and ten normal control subjects followed a
      protocol of typical daily activities and the whole period of the measurement was
      recorded by video. Walking periods were recognized using two sensors on shanks
      and lying periods were detected using a sensor on trunk. By calculating
      kinematics features of the trunk movements during the transitions between sitting
      and standing postures and using a statistical classifier, sit-to-stand (SiSt) and
      stand-to-sit (StSi) transitions were detected and separated from other body
      movements. Finally, a fuzzy classifier used this information to detect periods of
      sitting and standing. The proposed method showed a high sensitivity and
      specificity for the detection of basic body postures allocations: sitting,
      standing, lying, and walking periods, both in PD patients and healthy subjects.
      We found significant differences in parameters related to SiSt and StSi
      transitions between PD patients and controls and also between PD patients with
      and without STN-DBS turned on. We concluded that our method provides a simple,
      accurate, and effective means to objectively quantify physical activities in both
      normal and PD patients and may prove useful to assess the level of motor
      functions in the latter.

PMID- 18075048
TI  - [War and the stars: myth or reality in radiotherapy].

PMID- 18075047
TI  - Spectral analysis of motor unit action potentials.
AB  - The statistical processing of electromyographic signal examination performed in
      the time domain ensures mostly correct classification of pathology; however,
      because of an ambiguity of most temporal parameter definitions, a diagnosis can
      include a significant error that strongly depends on the neurologist's
      experience. Then, selected temporal parameters are determined for each run, and
      their mean values are calculated. In the final stage, these mean values are
      compared with a standard and, including additional clinical information, a
      diagnosis is given. An inconvenience of this procedure is high time consumption
      that arises from the necessity of determination of many parameters. Additionally,
      an ambiguity in determination of basic temporal parameters can cause doubts when
      parameters found by the physician are compared with standard parameters
      determined in other research centers. In this paper, we present a definition for
      spectral discriminant that directly enables a unique diagnosis to be made. An
      essential advantage of the suggested discriminant is a precise and
      algorithmically realized definition that enables an objective comparison of
      examination results obtained by physicians with different experiences or working
      in different research centers. A suggestion of the standard for selected muscle
      based on a population of 70 healthy cases is presented in the Results section.

PMID- 18075049
TI  - [The rebuilt face: ethics, techniques and results of the first face allograft].

PMID- 18075050
TI  - Heart failure: an epidemic of the XXIst century?

PMID- 18075051
TI  - [Multiparametric evaluation of cardiac risk in acute coronary syndromes: value of
      biological blood markers].
AB  - Appropriate evaluation of short- and medium-term cardiovascular risk in acute
      coronary syndromes (ACS) patients should allow to individualize and improve
      treatment in the future. Natriuretic peptides can be measured in plasma using
      reliable and fast methods. B-type natriuretic peptide (BNP) is released into the
      circulation by the cardiac ventricle in response to increases in wall stress.
      Both BNP and NT-proBNP have been shown to aid in the diagnosis of heart failure.
      In addition, these peptides correlate with left ventricular dilatation,
      remodelling and dysfunction, and have the capacity of improving significantly the
      early risk stratification in patients with ST- or non-ST-elevation ACS. BNP
      determinations can be associated to cardiac troponins (for example, cTnT) and C
      reactive protein (CRP). Plasma concentrations of these biomarkers are related to
      different physiopathological mechanisms: tissue necrosis (cTnT), neuro-hormonal
      activation (BNP, NT-proBNP) or inflammatory process and plaque instability (CRP).
      Combining two or three of these biomarkers for better risk stratification has the
      potential to improve substantially the outcomes in patients with ACS.

PMID- 18075052
TI  - The Hh signaling pathway in cancer.

PMID- 18075053
TI  - The receptor fingerprint of the human brain and its changes during life.
AB  - With the help of PET one can explore the various neurotransmitter-neuroreceptor
      systems, their interactive balance and their changes during life, i.e., the human
      brain receptor fingerprint: the highly individual composition of, and balance
      among, the various receptor systems can be measured both qualitatively (the
      presence of various receptors in different brain regions) and quantitatively (the
      density of the receptors, their binding potential, occupancy, etc.). The
      understanding of the normal constitution of the primate brain neurotransmitter
      receptor systems and their pathological changes requires multiligand receptor
      mapping, using various PET radioligands. Some major components of our brain
      receptor fingerprint strictly correlate with personality traits, character and
      temperament, and most probably, with "cognitive styles", as well. The brain
      receptor fingerprint is continuously changing during our normal life (maturation,
      ageing) and short term physiological or pharmacological challenges (sensory or
      cognitive processes, drug administration etc.) can also modify it. Social
      interactions, learning, habituation and other lasting interactions with our
      social and physical environment can significantly modify the receptor
      fingerprint. Pathological conditions, including neurological and psychiatric
      diseases strongly affect the normal neuroreceptor-neurotransmitter balance of the
      brain, as do pharmacological treatments or drug abuse.

PMID- 18075054
TI  - Transient receptor potential (TRP) cation channels: rewarding unique proteins.
AB  - The discovery of the Transient Receptor Potential (TRP) superfamily of versatile
      and polymodal cation channels has dramatically extended our molecular
      understanding of cellular sensors. The main surprising properties are their
      diversity in ion selectivity and the polymodal mechanisms of activation, which
      necessarily result in equally diverse cell functions. They are involved in
      sensory functions, e.g. the perception of temperature, smell, taste, pain,
      mechanical signals and respond to many natural compounds used in "traditional
      medicine". TRP channels are main players in Ca2+ signalling, which controls a
      plethora of events ranging from neurotransmitter release to gene transcription
      and cell death. They are also involved in homeostatic functions, e.g. epithelial
      Ca2+ and Mg2+ reabsorption and lysosomal pH regulation. TRP channel dysfunction
      contributes to certain human diseases. Finally, TRP channels will become
      important novel pharmacological targets for the treatment of human diseases and
      for modulation of sensory functions, e.g. the perception of flavor.

PMID- 18075055
TI  - Residents' mistakes can hurt you.

PMID- 18075056
TI  - Prior authorization made easier.

PMID- 18075057
TI  - Avoiding EHR sticker shock.

PMID- 18075058
TI  - CODE your way to better reimbursement.

PMID- 18075059
TI  - Identifying mercury's fingerprint.

PMID- 18075060
TI  - Have public-health research funds been diverted in the U.S.?

PMID- 18075061
TI  - Tamiflu survives sewage treatment.

PMID- 18075062
TI  - Are polar bears too polarizing?

PMID- 18075063
TI  - Biofueling water problems.

PMID- 18075064
TI  - Environmental problems and challenges in China.

PMID- 18075065
TI  - Metal flux and dynamic speciation at (bio)interfaces. Part I: Critical evaluation
      and compilation of physicochemical parameters for complexes with simple ligands
      and fulvic/humic substances.
AB  - In the computation of metal flux in aquatic systems, at consuming surfaces like
      organism membranes, diffusion processes of metal ions, ligands, and complex
      species, as well as the kinetic and thermodynamic aspects of their chemical
      interactions, must be considered. The properties of many natural ligands,
      however, are complicated (formation of successive complexes for simple ligands,
      polyelectrolytic properties and chemical heterogeneity for macromolecular
      ligands, large size distribution and fractal structure for suspended aggregates).
      These properties should be properly modeled to get the correct values of the
      chemical rate constants and diffusion coefficients required for flux
      computations. The selection of the most appropriate models and parameter values
      is far from straightforward. This series of papers discusses the various models
      and compiles the parameters needed for the three most important types of
      complexants found in aquatic systems: the small, simple ligands, the fulvic and
      humic compounds, and the colloidal "particles" or aggregates. In particular, new
      approaches are presented to compute the rate constants of metal complex
      formation, with both fulvics/humics and particles/aggregates. The method to
      include the site distribution of fulvics/humics and the size distribution of
      particles/aggregates in metal flux computation at consuming interfaces is also
      discussed in detail. These models and parameters are discussed critically and
      presented in the same framework, forthe computation of metal flux in presence of
      any of the above complexants or mixtures. Such parameters, largely spread in the
      literature, are gathered here and selected specifically for environmental
      applications. The focus in Part I of the series is on simple ligands and
      fulvic/humic compounds. Part II deals with particulate and aggregate complexants.

PMID- 18075066
TI  - Metal flux and dynamic speciation at (bio)interfaces. Part II: Evaluation and
      compilation of physicochemical parameters for complexes with particles and
      aggregates.
AB  - The computation of metal flux in aquatic systems at consuming surfaces like
      organism membranes must consider the diffusion processes of metal ions, ligands,
      and complex species, as well as the kinetic and thermodynamic aspects of their
      chemical interactions. Many natural ligands, however, have complicated properties
      (formation of successive complexes for simple ligands, polyelectrolytic
      properties and chemical heterogeneity for macromolecular ligands, large size
      distribution and fractal structure for suspended aggregates). These properties
      should be properly modeled to get the correct values of the chemical rate
      constants and diffusion coefficients required for flux computations. The
      selection of the most appropriate models and parameter values is far from
      straightforward. In this series of papers, models and compilations of parameters
      for application to the three most important types of complexants found in aquatic
      systems, the small, simple ligands, the fulvic and humic compounds, and the
      colloidal "particles" or aggregates, are discussed. In particular, new approaches
      are presented to compute the rate constants of metal complex formation for both
      fulvics/humics and particles/aggregates. A method to include the site
      distribution of fulvics/ humics and the size distribution of particles/aggregates
      in metal flux computation at consuming interfaces is also discussed in detail.
      These models and parameters are discussed critically and presented in a single
      consistent framework, applicable to the computation of metal flux in presence of
      any of the above complexants ortheir mixtures. Part I of the series focuses on
      simple ligands and fulvic/ humic compounds. Part II deals with particulate and
      aggregate complexants.

PMID- 18075067
TI  - Atmospheric transport of mercury to the Tibetan Plateau.
AB  - The Tibetan Plateau (including the Himalayas) is one of the most remote and cold
      regions in the world. It has very limited to nonexistent industry but is adjacent
      to the two most populous and rapidly industrializing countries (China and India)
      and thus provides a unique location for studying the atmospheric transport of
      mercury. Here we report the first study on the atmospheric transport of mercury
      to the Tibetan Plateau. The total mercury profiles in four snowpits from glaciers
      above 5700 m asl along a southwest-northeast transect across the central Tibetan
      Plateau were obtained in 2005-2006. In general, the total mercury concentrations
      in the snow samples ranged from < 1 to 9 ng L(-1), increasing northeastward from
      the southernmost site at Mount Everest. Higher total mercury concentrations were
      found in the snow deposited in the nonmonsoon season, as indicated by seasonal
      variation of delta18O values and major ions in the snowpack. The annual
      atmospheric depositional flux of total Hg was estimated to range from 0.74 to
      2.97 microg m(-2) yr(-1) in the region, the majority of which occurred via
      particulate matter deposition.

PMID- 18075068
TI  - Atmospheric atrazine at Canadian IADN sites.
AB  - Atrazine is one of the most widely used herbicides in North America and has been
      primarily applied to corn production in the Great Lakes basin for over 30 years.
      During 1996-2002, atrazine concentrations in the atmospheric gas and particle
      phases were investigated at three Canadian Integrated Atmospheric Deposition
      Network (IADN) sites including two lakeside sites (Burnt Island and Point Petre)
      and a rural inland site (Egbert). Strong seasonality with peak concentrations
      occurring in late April-early July was observed. An atrazine usage map for Canada
      (sum: 870 t) and the United States (sum: 34 500 t) in 2002 was created. Local
      application and regional atmospheric transport both appear to contribute to its
      atmospheric occurrence, while the latter might episodically result in high
      concentrations events. No strong temperature dependence was observed for atrazine
      particle-gas partitioning. Recent measurement results of atrazine in
      precipitation samples collected at Egbert and another agricultural site,
      Vineland, through the Canadian Atmospheric Network for Currently Used Pesticides
      (CANCUP), are also presented, Dry, wet, and gas exchange deposition all
      contribute to atmospheric inputs of atrazine to the Great Lakes. For Lake
      Ontario, gas exchange is estimated to be of similar magnitude to dry and wet
      deposition.

PMID- 18075069
TI  - Watershed sources of disinfection byproduct precursors in the Sacramento and San
      Joaquin Rivers, California.
AB  - High levels of dissolved organic carbon (DOC) and bromide (Br) in the Sacramento
      and San Joaquin River waterways are of concern because DOC and Br are organic and
      inorganic precursors, respectively, of carcinogenic and mutagenic disinfection
      byproducts (DBPs). The Sacramento and San Joaquin Rivers are the two major rivers
      supplying water to the San Francisco Bay Delta, but sources and loads of DBP
      precursors into the Delta are still uncertain. The major objectives of this study
      were to evaluate both the quantity (DOC and Br fluxes) and the quality
      (reactivity in forming DBPs) of DBP precursors from the Sacramento and San
      Joaquin watersheds. Water samples were collected every 2 weeks at up to 35
      locations along the Sacramento and San Joaquin Rivers and selected tributaries
      and analyzed for DOC (4 years), Br (1 year), and ultraviolet absorbance at 254 nm
      (1 year). Selected water samples were also tested for THM formation potential.
      Estimated fluxes for the Sacramento River were 39 000 +/- 12 000 Mg DOC year(-1)
      and 59 Mg of Br year(-1) as compared to 9000 +/- 5000 Mg of DOC year(-1) and 1302
      Mg of Br year(-1) for the San Joaquin River. The THM formation potential was
      higher in the San Joaquin River (441 +/- 49 microg L(-1)) than the Sacramento
      River (176 +/- 20 microg L(-1)) because of higher concentrations of both organic
      (DOC = 3.62 +/- 0.14 vs 1.92 +/- 0.09 mg L(-1)) and inorganic DBP (Br = 0.80 +/-
      0.07 vs < 0.03 +/- 0.01 mg L(-1)) precursors. The Sacramento River's greater DOC
      load despite lower DOC concentrations is due to its discharge being about 5 times
      greater than the San Joaquin River (50 x 10(9) vs 10 x 10(9) L day(-1)). The DOC
      concentration was significantly correlated with several land-cover types,
      including agriculture; however, no relationship was found between DOC quality and
      land-cover at the watershed scale.

PMID- 18075070
TI  - Uranium deposition in a weathered fractured saprolite/shale.
AB  - Chemical analysis and scanning electron microscopy (SEM) microanalysis were
      carried out on cores of contaminated geological material collected around four
      closed waste disposal ponds to examine the extent of nitric acid extractable U
      (U(NA)) association with P, S, and extractable Fe, Al, and Mn oxides within
      deeply weathered fractured shale. The solid phase in many regimes on the site has
      been exposed to highly buffered acidic (< 3.5) groundwater and has been
      aggressively weathered. Higher correlations occur between U(NA) and total P and S
      (r2 = 0.76, 0.69, respectively), citrate bicarbonate dithionite extractable Fe
      (Fed) and Al (Ald) (r2 = 0.87, 0.80, respectively), and acid oxalate extractable
      or amorphous/poorly crystalline Fe (Feo) (r2 = 0.63) in core material from a
      field plot known as Area 1 compared to core material from another field plot
      known as Area 3. In Area 3 core material, linear regression analysis of U(NA) and
      total P and S, and Fed, Ald and Feo gave r2 values of 0.67, 0.4, 0.06, 0.24, and
      0.45, respectively. These results showed similar relationships with SEM
      wavelength dispersive spectroscopy (WDS) mapping of this material. It is
      noteworthy that Area 1 geological material has not been as aggressively weathered
      as Area 3 material due to its physical location from the waste source. In all of
      the cores, most of the Fe and Al oxides were crystalline, while most of the Mn
      oxides were amorphous. The greater adsorption and/or fixation of anion complexes
      of P-U (uranium phosphate) and S onto Fe and Al oxides from Area 1 cores compared
      to Area 3 core material is probably due to a higher amount of crystalline Fe and
      Al oxides compared to amorphous Fe and Al oxides and higher Al substitution in Fe
      oxides in Area 1. This unique study illustrates the relationships between U(NA),
      total P and S, and Al, Fe and Mn oxides in fractured shale under field conditions
      which can be used in planning remediation of this site and other similar sites.

PMID- 18075071
TI  - Nitrogen isotopes as indicators of NO(x) source contributions to atmospheric
      nitrate deposition across the midwestern and northeastern United States.
AB  - Global inputs of NO(x) are dominated by fossil fuel combustion from both
      stationary and vehicular sources and far exceed natural NO(x) sources. However,
      elucidating NO(x) sources to any given location remains a difficult challenge,
      despite the need for this information to develop sound regulatory and mitigation
      strategies. We present results from a regional-scale study of nitrogen isotopes
      (delta15N) in wet nitrate deposition across 33 sites in the midwestern and
      northeastern U.S. We demonstrate that spatial variations in delta15N are strongly
      correlated with NO(x) emissions from surrounding stationary sources and
      additionally that delta15N is more strongly correlated with surrounding
      stationary source NO(x) emissions than pH, SO4(2-), or NO3- concentrations.
      Although emission inventories indicate that vehicle emissions are the dominant
      NO(x) source in the eastern U.S., our results suggest that wet NO3- deposition at
      sites in this study is strongly associated with NO(x) emissions from stationary
      sources. This suggests that large areas of the landscape potentially receive
      atmospheric NO(y) deposition inputs in excess of what one would infer from
      existing monitoring data alone. Moreover, we determined that spatial patterns in
      delta15N values are a robust indicator of stationary NO(x) contributions to wet
      NO3- deposition and hence a valuable complement to existing tools for assessing
      relationships between NO3- deposition, regional emission inventories, and for
      evaluating progress toward NO(x) reduction goals.

PMID- 18075072
TI  - Body loadings and health risk assessment of polychlorinated dibenzo-p-dioxins and
      dibenzofurans at an intensive electronic waste recycling site in China.
AB  - This study is one of the very few investigating the dioxin body burden of a group
      of child-bearing-aged women at an electronic waste (e-waste) recycling site
      (Taizhou, Zhejiang Province) (24 +/- 2.83 years of age, 40% were primiparae) and
      a reference site (Lin'an city, Zhejiang Province, about 245 km away from Taizhou)
      (24 +/- 2.35 years of age, 100% were primiparae) in China. Five sets of samples
      (each set consisted of human milk, placenta, and hair) were collected from each
      site. Body burdens of people from the e-waste processing site (human milk, 21.02
      +/- 13.81 pg WHO-TEQ1998/g fat (World Health Organization toxic equivalency
      1998); placenta, 31.15 +/- 15.67 pg WHO-TEQ1998/g fat; hair, 33.82 +/- 17.74 pg
      WHO-TEQ1998/g dry wt) showed significantly higher levels of polychlorinated
      dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/ Fs) than those from
      the reference site (human milk, 9.35 +/- 7.39 pg WHO-TEQ1998/g fat; placenta,
      11.91 +/- 7.05 pg WHO-TEQ1998/g fat; hair, 5.59 +/- 4.36 pg WHO-TEQ1998/g dry wt)
      and were comparatively higher than other studies. The difference between the two
      sites was due to e-waste recycling operations, for example, open burning, which
      led to high background levels. Moreover, mothers from the e-waste recycling site
      consumed more foods of animal origin. The estimated daily intake of PCDD/Fs
      within 6 months by breastfed infants from the e-waste processing site was 2 times
      higher than that from the reference site. Both values exceeded the WHO tolerable
      daily intake for adults by at least 25 and 11 times, respectively. Our results
      implicated that e-waste recycling operations cause prominent PCDD/F levels in the
      environment and in humans. The elevated body burden may have health implications
      for the next generation.

PMID- 18075073
TI  - Factors influencing mobile source particulate matter emissions-to-exposure
      relationships in the Boston urban area.
AB  - Benefit-cost and regulatory impact analyses often use atmospheric dispersion
      models with coarse resolution to estimate the benefits of proposed mobile source
      emission control regulations. This approach may bias health estimates or miss
      important intra-urban variability for primary air pollutants. In this study, we
      estimate primary fine particulate matter (PM2.5) intake fractions (iF; the
      fraction of a pollutant emitted from a source that is inhaled by the population)
      for each of 23 398 road segments in the Boston Metro Core area to evaluate the
      potential for intra-urban variability in the emissions-to-exposure relationship.
      We estimate iFs using the CAL3QHCR line source model combined with residential
      populations within 5000 m of each road segment. The annual average values for the
      road segments range from 0.8 to 53 per million, with a mean of 12 per million. On
      average, 46% of the total exposure is realized within 200 m of the road segment,
      though this varies from 0 to 93% largely due to variable population patterns. Our
      findings indicate the likelihood of substantial intra-urban variability in mobile
      source primary PM2.5 iF that accounting for population movement with time,
      localized meteorological conditions, and street-canyon configurations would
      likely increase.

PMID- 18075074
TI  - Speciation of selenium in stream insects using X-ray absorption spectroscopy.
AB  - Selenium contamination in the environment is a widespread problem affecting
      insects and other wildlife. Insects occupy a critical middle link and aid in
      trophic transfer of selenium in many terrestrial and freshwater food chains, but
      the mechanisms of selenium uptake through the food chain are poorly understood.
      In particular, biotransformation of selenium by insects into different chemical
      forms will greatly influence how toxic or benign the selenium is to that organism
      or to its predators. We have used X-ray absorption spectroscopy (XAS) to identify
      the chemical form of selenium in insects inhabiting selenium contaminated streams
      near Hinton, Alberta (Canada). Selenium K near-edge spectra indicate a
      variability of selenium speciation among the insects that included mayflies
      (Ephemeroptera), stoneflies (Plecoptera), caddisflies (Trichoptera), and
      craneflies (Diptera). Higher percentages of inorganic selenium were observed in
      primary consumers, detritivores, and filter feeders than in predatory insects.
      Among the organic forms of selenium, organic selenides constituted a major
      fraction in most organisms. A species modeled as trimethylselenonium was observed
      during the pupal stage of caddisflies. These results provide insights into how
      the insects cope with their toxic cargo, including how the selenium is
      biotransformed into less toxic forms and how it can be eliminated from the
      insects. More broadly, this study demonstrates the strengths of XAS to probe the
      effects of heavy elements at trace levels in insects from the field.

PMID- 18075075
TI  - Anthropogenically driven changes in chloride complicate interpretation of base
      cation trends in lakes recovering from acidic deposition.
AB  - Declines in Ca and Mg in low ANC lakes recovering from acidic deposition are
      widespread across the northern hemisphere. We report overall increases between
      1984 and 2004 in the concentrations of Ca + Mg and Cl in lakes representing the
      statistical population of nearly 4000 low ANC lakes in the northeast U.S.
      Increases in Cl occurred in nearly all lakes in urbanized southern New England,
      but only 18% of lakes in more remote Maine had Cl increases. This spatial pattern
      implicates road salt application as the major source of the increased Cl salts.
      Among the 48% of the lake population classified as salt-affected, the median
      changes in Cl (+133 microeq/L) and Ca + Mg (+47 microeq/ L) were large and
      positive in direction over the 20 years. However, in the unaffected lakes, Cl
      remained stable and Ca + Mg decreased (-3 microeq/L), consistent with reported
      long-term trends in base cations of acid-sensitive lakes. This discrepancy
      between the Cl groups suggests that changes in ion exchange processes in salt
      affected watersheds have altered the geochemical cycling of Ca and Mg. One policy
      relevant implication is that waters influenced by Cl salts complicate regional
      assessments of surface water recovery from "acid rain" related to the passage of
      the Clean Air Act.

PMID- 18075076
TI  - Detection of dechlorane plus in residential indoor dust in the city of Ottawa,
      Canada.
AB  - Dechlorane plus (DP), a flame retardant recently identified in the air and
      sediment of the Great Lakes region, has been detected in residential indoor dust
      in the city of Ottawa, Canada using gas chromatography-mass spectrometry under
      negative chemical ionization mode. DP was detected in all dust samples with a
      concentration range of 2.3 to 182 ng g(-1), except for one dust sample (5683 ng
      g(-1)) which was much higher. The levels of DP in indoor dust were several times
      higher than those in the sediment of the Great Lakes. The presence of DP in
      indoor environments could have implications for potential human exposure to this
      chemical. The daily human intake of DP from dust was estimated using dust
      ingestion data from the U.S. Environmental Protection Agency. The large variation
      of the ratio of syn- and anti-DP isomers in the dust samples also suggests a
      complex degradation process of DP in the environment.

PMID- 18075077
TI  - Sorption of mercuric ion by synthetic nanocrystalline mackinawite (FeS).
AB  - Iron sulfides are known to be efficient scavengers of heavy metals. In this
      study, Hg(II) sorption was investigated using synthetic nanocrystalline
      mackinawite (a disordered phase) as a function of initial Hg(II) concentration
      [Hg(II)]0, initial FeS concentration [FeS]0, total chloride concentration CIT,
      and pH. Hg(II) sorption mechanisms are dependent on relative concentrations of
      [Hg(II)]0 and [FeS]0 (the molar ratio of [Hg(II)0/[FeS]0). When the molar ratio
      of [Hg(II)]0/[FeS]o is as low as 0.05, adsorption is mainly responsible for
      Hg(II) removal, with its contribution to the overall sorption increasing at lower
      Cl(T). As the molar ratio increases, the adsorption capacity becomes saturated,
      resulting in precipitation of a sparingly soluble HgS(s). XRD analysis indicates
      formation of metacinnabar (beta-HgS). Concurrently with HgS(s) precipitation, the
      released Fe(II) from FeS(s) is resorbed by adsorption at acidic pH and either
      adsorption or precipitation as Fe (hydr)-oxides at neutral to basic pH.
      Subsequently, the Fe precipitate formed at neutral to basic pH serves as an
      adsorbent for Hg(II). Under the conditions where either adsorption or HgS(s)
      precipitation is dominant, more than 99% of [Hg(II)]0 is immobilized. When the
      molar ratio of [Hg(II)]0/[FeS]0 exceeds 1, the sulfide concentration is no longer
      sufficient for HgS(s) precipitation, and formation of chloride salts (Hg2Cl2 at
      acidic pH and HgCl2 x 3HgO at basic pH) occurs.

PMID- 18075078
TI  - Long-term increase in dissolved organic carbon in streamwaters in Norway is
      response to reduced acid deposition.
AB  - Concentrations of dissolved organic carbon (DOC) in freshwaters have increased
      significantly in Europe and North America, but the driving mechanisms are poorly
      understood. Here, we test if the significant increase in TOC (total organic
      carbon, 90-95% DOC) in three acid-sensitive catchments in Norway of 14 to 36%
      between 1985 and 2003 is related to climate, hydrology, and/or acid deposition.
      Catchment TOC export increased between 10 and 53%, which was significant at one
      site only. The seasonal variation in TOC was primarily climatically controlled,
      while the deposition of SO4 and NO3--negatively related to TOC--explained the
      long-term increase in TOC. We propose increased humic charge and reduced ionic
      strength--both of which increase organic matter solubility--as mechanistic
      explanations for the statistical relation between reduced acid deposition and
      increased TOC. Between 1985 and 2003, ionic strength decreased significantly at
      all sites, while the charge density of TOC increased at two of the sites from 1-2
      meq g(-1) C to about 5 meq g(-1) C and remained constant at the third site at 5
      meq g(-1) C. The solubility of organic matter is discussed in terms of the pH
      dependent deprotonation of carboxylic groups and the ionic strength-dependent
      repulsion of organic molecules.

PMID- 18075079
TI  - Attenuation of fluorocarbons released from foam insulation in landfills.
AB  - Chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), and
      hydrofluorocarbons (HFCs) have been used as blowing agents (BAs) for foam
      insulation in home appliances and building materials, which after the end of
      their useful life are disposed of in landfills. The objective of this project was
      to evaluate the potential for degradation of BAs in landfills, and to develop a
      landfill model, which could simulate the fate of BAs in landfills. The
      investigation was performed by use of anaerobic microcosm studies using different
      types of organic waste and anaerobic digested sludge as inoculum. The BAs studied
      were CFC-11, CFC-12, HCFC-141b, HFC-134a, and HFC-245fa. Experiments considering
      the fate of some of the expected degradations products of CFC-11 and CFC-12 were
      included like HCFC-21, HCFC-22, HCFC-31, HCFC-32, and HFC-41. Degradation of all
      studied CFCs and HCFCs was observed regardless the type of waste used. In
      general, the degradation followed first-order kinetics. CFC-11 was rapidly
      degraded from 590 microg L(-1) to less than 5 microg L(-1) within 15-20 days. The
      degradation pattern indicated a sequential production of HCFC-21, HCFC-31, and
      HFC-41. However, the production of degradation products did not correlate with a
      stoichiometric removal of CFC-11 indicating that other degradation products were
      produced. HCFC-21 and HCFC-31 were further degraded whereas no further
      degradation of HFC-41 was observed. The degradation rate coefficient was directly
      correlated with the number of chlorine atoms attached to the carbon. The highest
      degradation rate coefficient was obtained for CFC-11, whereas lower rates were
      seen for HCFC-21 and HCFC-31. Equivalent results were obtained for CFC-12. HCFC
      141b was also degraded with rates comparable to HCFC-21 and CFC-12. Anaerobic
      degradation of the studied HFCs was not observed in any of the experiments within
      a run time of up to 200 days. The obtained degradation rate coefficients were
      used as input for an extended version of an existing landfill fate model
      incorporating a time dependent BA release from co-disposed foam insulation waste.
      Predictions with the model indicate that the emission of foam released BAs may be
      strongly attenuated by microbial degradation reactions. Sensitivity analysis
      suggests that there is a need for determination of degradation rates under more
      field realistic scenarios.

PMID- 18075080
TI  - Persistent chlordane concentrations in Long Island Sound sediment: implications
      from chlordane, 210Pb, and 137Cs profiles.
AB  - Concentrations of chlordane, a banned termiticide and pesticide, were examined in
      recently collected surficial sediment (10 sites) and sediment cores (4 sites) in
      Long Island Sound (LIS). The highest chlordane concentrations were observed in
      western LIS, near highly urbanized areas. Chlordane concentrations did not
      decrease significantly in the past decade when compared to the data collected in
      1996, consistent with the observation of near-constant chlordane levels in blue
      mussel tissues collected during the same time period. Chlordane concentrations in
      many of the sites exceeded levels above which harmful effects on sediment
      dwelling organisms are expected to frequently occur. Chlordane concentrations in
      two of the four sediment cores showed a peak below the sediment surface,
      suggesting reduced chlordane inputs in recent years. The lack of a chlordane
      concentration maximum below the sediment surface in the other two cores, coupled
      with the lack of a well-defined 137Cs peak, indicated significant sediment
      mixing. Simulations of 137Cs and 210Pb profiles in sediment cores with a simple
      sediment-mixing model were used to constrain both the deposition rate and the
      bioturbation rate of the sediment. Simulations of the chlordane profiles
      indicated continued chlordane input to LIS long after chlordane was phased out in
      the U.S. Continued chlordane input and significant sediment mixing may have
      contributed to the persistent chlordane concentrations in surficial sediment,
      which poses long-term threats to benthic organisms in LIS.

PMID- 18075081
TI  - Kinetics of reductive dissolution of hematite by bioreduced anthraquinone-2,6
      disulfonate.
AB  - The reductive dissolution of hematite (alpha-Fe2O3) was investigated in a flow
      through system using AH2DS, a reduced form of anthraquinone-2,6-disulfonate
      (AQDS), which is often used as a model electron shuttling compound in studies of
      dissimilatory microbial reduction of iron oxides. Influent flow rate, pH, and
      Fe(II) and phosphate concentrations were varied to investigate the redox kinetics
      in a flow-through reactor. The hematite reduction rates decreased with increasing
      pH from 4.5 to 7.6 and decreased with decreasing flow rate. The rates also
      decreased with increasing influent concentration of Fe(II) or phosphate that
      formed surface complexes at the experimental pH. Mineral surface properties,
      Fe(II) complexation reactions, and ADDS sorption on hematite surfaces were
      independently investigated for interpreting hematite reduction kinetics. AH2DS
      sorption to hematite was inferred from the parallel measurements of AQDS and
      AH2DS sorption to alpha-Al2O3, a redox stable analog of alpha-Fe2O3. Decreasing
      Fe(ll) and increasing AH2DS sorption by controlling flow rate, influent pH, and
      Fe(II) and phosphate concentrations increased the rates of reductive dissolution.
      The rates were also affected by the redox reaction free energy when reductive
      dissolution approached equilibrium. This study demonstrated the importance of the
      geochemical variables for the reductive dissolution kinetics of iron oxides.

PMID- 18075082
TI  - Reductive dechlorination pathways of tetrachloroethylene and trichloroethylene
      and subsequent transformation of their dechlorination products by mackinawite
      (FeS) in the presence of metals.
AB  - Because of frequent co-occurrence of metals with chlorinated organic pollutants,
      Fe(II), Co(II), Ni(II), and Hg(II) were evaluated for their impact on the
      dechlorination pathways of PCE and TCE and the subsequent transformation of the
      initial dechlorination products by FeS. PCE transforms to acetylene via beta
      elimination, TCE via hydrogenolysis, and 1,1-DCE via alpha-elimination, while TCE
      transforms to acetylene via beta-elimination and cis-DCE and 1,1-DCE via
      hydrogenolysis. Acetylene subsequently transforms in FeS batches, but little
      transformation of cis-DCE and 1,1-DCE was observed. Branching ratio calculations
      indicate that the added metals decrease the reductive transformation of PCE and
      TCE via beta-elimination relative to hydrogenolysis, resulting in a higher
      production of the toxic DCE byproducts. Nonetheless, acetylene is generally the
      dominant product. Production of highly water-soluble compound(s) is suspected as
      a significant source for incomplete mass recoveries. In the transformation of PCE
      and TCE, the formation of unidentified product(s) is most significant in Co(II)
      added FeS batches. Although nearly complete mass recoveries were observed in the
      other FeS batches, the subsequent transformation of acetylene would lead to the
      formation of unidentified product(s) over long time periods.

PMID- 18075083
TI  - Microbial dehalogenation of trichlorinated dibenzo-p-dioxins by a Dehalococcoides
      containing mixed culture is coupled to carbon isotope fractionation.
AB  - An anaerobic enrichment culture reductively dehalogenated 1,2,4- and 1,2,3
      trichlorodibenzo-p-dioxin (TrCDD) almost exclusively at peripheral positions
      forming the main products 1,3-dichloro-(DiCDD) and 2-monochlorodibenzo-p-dioxin
      (MCDD) from 1,2,4-TrCDD and 2,3-DiCDD from 1,2,3-TrCDD. Dehalococcoides was
      monitored in the mixed culture by quantitative real-time PCR. A yield of 2.5 x
      10(8) to 2.75 x 10(8) copies of 16S rRNA genes per micromole of chloride released
      suggested growth by dehalorespiration with dibenzo-p-dioxins. For the analysis of
      carbon isotope fractionation, the dioxin congeners were isolated by solid-phase
      microextraction (SPME) from the headspace of the cultures. The delta13C
      composition of 1,2,4-TrCDD did not change remarkably during the course of
      reductive dehalogenation; however, the intermediate 1,3-DiCDD became enriched,
      and the final product 2-MCDD significantly depleted in 13C with a discrimination
      of 2.5-3.6 per thousand between 1,3-DiCDD and 2-MCDD. 1,2,3-TrCDD and its main
      product 2,3-DiCDD became slightly enriched in 13C, whereas the formed low
      concentrations of 2-MCDD were depleted in 13C by 5.5-4.8 per thousand. This study
      demonstrates carbon isotope fractionation during sequential reductive
      dehalogenation of chlorinated dibenzo-p-dioxins, whereby isotope fractionation
      upon dehalogenation of the intermediate was substantial. This can provide a basis
      for the development of a new method to monitor the fate of dioxins in the
      environment using compound specific stable isotope analyses.

PMID- 18075084
TI  - Investigating desorption of native pyrene from sediment on minute- to month
      timescales by time-gated fluorescence spectroscopy.
AB  - We investigated desorption of native pyrene from field-aged sediments using time
      gated, laser-induced fluorescence (LIF) spectroscopy. LIF is superior to
      conventional analytical methods for the measurement of quickly changing dissolved
      pyrene because it allows observations at minute-scale resolution, has a low
      detection limit (approximately 1 ng/L), and minimizes sample loss and disturbance
      since it requires no system subsampling and chemical analysis. The efficacy of
      LIF was demonstrated in studies of pyrene desorption from Boston Harbor sediment
      segregated into different size-fractions (38-75, 75-106, and 180-250 microm
      diameter) and used in varying solid-to-water ratios (20, 70, and 280
      mg(solid)/L). The effects of particle size and solid loading on desorption were
      consistent with diffusion physics. For suspension conditions between 20 and 280
      mg(solids)/L, we observed desorption continuing toward an apparent plateau level
      over the course of weeks to months. This implies that the characteristic
      desorption time of pyrene from fine sediments and, by inference, other sediment
      bound hydrophobic organic compounds (HOCs) of similar hydrophobicity, exceeds the
      typical characteristic times for pore water flushing and resuspension events.
      Consequently, the assumption of local sorption equilibrium in modeling efforts
      would be inappropriate.

PMID- 18075085
TI  - Potential for plastics to transport hydrophobic contaminants.
AB  - Plastic debris litters marine and terrestrial habitats worldwide. It is ingested
      by numerous species of animals, causing deleterious physical effects. High
      concentrations of hydrophobic organic contaminants have also been measured on
      plastic debris collected from the environment, but the fate of these contaminants
      is poorly understood. Here, we examine the uptake and subsequent release of
      phenanthrene by three plastics. Equilibrium distribution coefficients for
      sorption of phenanthrene from seawater onto the plastics varied by more than an
      order of magnitude (polyethylene >> polypropylene > polyvinyl chloride (PVC)). In
      all cases, sorption to plastics greatly exceeded sorption to two natural
      sediments. Desorption rates of phenanthrene from the plastics or sediments back
      into solution spanned several orders of magnitude. As expected, desorption
      occurred more rapidly from the sediments than from the plastics. Using the
      equilibrium partitioning method, the effects of adding very small quantities of
      plastic with sorbed phenanthrene to sediment inhabited by the lugworm (Arenicola
      marina) were evaluated. We estimate that the addition of as little as 1 microg of
      contaminated polyethylene to a gram of sediment would give a significant increase
      in phenanthrene accumulation by A. marina. Thus, plastics may be important agents
      in the transport of hydrophobic contaminants to sediment-dwelling organisms.

PMID- 18075086
TI  - Iron-mediated microbial oxidation and abiotic reduction of organic contaminants
      under anoxic conditions.
AB  - In anoxic environments, the oxidation of organic compounds, such as BTEX fuel
      components, by dissimilatory Fe(III) reduction can generate reactive mineral
      bound Fe(II) species, which in turn are able to reduce other classes of organic
      and inorganic groundwater contaminants. In this study, we designed and evaluated
      an anaerobic batch reactor that mimicks iron-reducing conditions to investigate
      the factors that favor the coupling of microbial toluene oxidation and abiotic
      reduction of nitroaromatic contaminants. We investigated the influence of
      different Fe(III)-bearing minerals and combinations thereof on the coupling of
      these two processes. Results from laboratory model systems show that complete
      oxidation of toluene to CO2 by Geobacter metallireducens in the presence of
      Fe(III)-bearing minerals leads to the formation of mineral-bound Fe(II) species
      capable of the reduction of 4-nitroacetophenone. Whereas significant microbial
      toluene oxidation was only observed in the presence of amorphous Fe(III) phases,
      reduction of nitroaromatic compounds only proceeded with Fe(II) species bound to
      crystalline Fe(III) oxides. Our results suggest that in anoxic soils and
      sediments containing amorphous and crystalline iron phases simultaneously,
      coupling of microbial oxidation and abiotic reduction of organic compounds may
      allow for concurrent natural attenuation of different contaminant classes.

PMID- 18075087
TI  - Assessing iron-mediated oxidation of toluene and reduction of nitroaromatic
      contaminants in anoxic environments using compound-specific isotope analysis.
AB  - We evaluated compound-specific isotope analysis (CSIA) as a tool to assess the
      coupling of microbial toluene oxidation by Fe(III)-reducing bacteria and abiotic
      reduction of nitroaromatic contaminants by biogenic mineral-bound Fe(II) species.
      Examination of the two processes in isolated systems revealed a reproducible
      carbon isotope fractionation for toluene oxidation by Geobacter metal-lireducens
      with a solid Fe(III) phase as terminal electron acceptor. We found a carbon
      isotope enrichment factor, epsilonC, of -1.0 +/- 0.1 per thousand, which
      corresponds to an apparent kinetic isotope effect (AKIE(C)) of 1.0073 +/- 0.0009
      for the oxidative cleavage of a C-H bond. Nitrogen isotope fractionation of the
      reduction of nitroaromatic compounds (NAC) by mineral-bound Fe(ll) species
      yielded a nitrogen isotope enrichment factor, epsilonN, of -39.7 +/- 3.4 per
      thousand for the reduction of an aromatic NO2-group (AKIE(N) = 1.0413 +/- 0.0037)
      that was constant for variable experimental conditions. Finally, AKIE values for
      C and N observed in coupled experiments, where reactive Fe(II) was generated
      through microbial activity, were identical to those obtained in the isolated
      experiments. This study provides new evidence on isotope fractionation behavior
      during contaminant transformation and promotes the use of CSIA for the
      elucidation of complex contaminant transformation pathways in the environment.

PMID- 18075088
TI  - Spectroscopic investigation of the uptake of arsenite from solution by synthetic
      mackinawite.
AB  - As(III) uptake from solution by synthetic mackinawite is examined as a function
      of pH and initial As(III) concentration using X-ray absorption spectroscopy (XAS)
      and X-ray diffraction (XRD). XAS data indicate that when mackinawite is reacted
      at pH 5, 7, and 9 with 5 x 10(-4) M As(III), arsenic is reduced from its original
      +3 valence state and is primarily coordinated as As-S (approximately 2.26
      angstroms) and As-As (approximately 2.54 angstroms), which is consistent with the
      formation of a realgar-like phase in agreement with XRD data. At 5 x 10(-5) M
      As(III), samples are markedly different from those collected at an order of
      magnitude higher concentration and differ at each pH value. The XAS analysis of
      mackinawite samples reacted with 5 x 10(-5) M As(III) shows a transition from As
      O coordination to As-S coordination as pH decreases, with the sample reacted at
      pH 5 resembling realgar. Under alkaline conditions, arsenic retains its original
      valence state of +3 and is primarily coordinated to oxygen at a distance of 1.75
      angstroms. This may be attributed to uptake by adsorption as an As(III) oxyanion.
      These results provide the basis for selecting the reactions needed for modeling
      and are beneficial in understanding the mechanisms of arsenite uptake by
      mackinawite under anoxic sulfidic conditions.

PMID- 18075089
TI  - Significance of Chloroflexi in performance of submerged membrane bioreactors
      (MBR) treating municipal wastewater.
AB  - We operated pilot-scale submerged membrane bioreactors (MBR) treating real
      municipal wastewater for over 3 months and observed an interesting phenomenon
      that carbohydrate concentrations in the MBRs rapidly increased, which
      consequently resulted in membrane fouling, when relative abundance of the member
      of uncultured Chloroflexi decreased from over 30% of total Bacteria to less than
      10%. We, therefore, hypothesized that the uncultured Chloroflexi present in the
      MBRs could preferentially degrade carbohydrates and consequently prevent membrane
      fouling. To test this hypothesis, we investigated the phylogenetic identity,
      diversity, and in situ physiology (substrate utilization characteristics) of
      Chloroflexi residing in the MBR by using 16S rRNA gene sequencing analysis and
      microautoradiography combined with fluorescence in situ hybridization (MAR-FISH)
      technique. Most of the clones related to the phylum Chloroflexiwere affiliated
      with the Chloroflexi subphylum 1 containing only a few cultured representatives.
      The MAR-FISH revealed that the members of Chloroflexi were metabolically
      versatile and could preferentially utilize glucose and N-acetyl glucosamine (a
      main substantial constituent of the cell wall peptidoglycan) under oxic and
      anoxic conditions. The utilization of these compounds was low at low pH. These
      findings suggest that the members of Chloroflexi are ecologically significant in
      the MBR treating municipal wastewater and are responsible for degradation of SMP
      including carbohydrates and cellular materials, which consequently reduces
      membrane fouling potential.

PMID- 18075090
TI  - Chemical kinetic and molecular genetic study of selenium oxyanion reduction by
      Enterobacter cloacae SLD1a-1.
AB  - Microbial processes play an important role in the redox transformations of toxic
      selenium oxyanions. In this study, we employed chemical kinetic and molecular
      genetic techniques to investigate the mechanisms of Se(IV) and Se-(VI) reduction
      by the facultative anaerobe Enterobacter cloacae SLD1a-1. The rates of microbial
      selenium oxyanion reduction were measured as a function of initial selenium
      oxyanion concentration (0-1.0 mM) and temperature (10-40 degrees C), and
      mutagenesis studies were performed to identify the genes involved in the selenium
      oxyanion reduction pathway. The results indicate that Se(IV) reduction is
      significantly more rapid than the reduction of Se(VI). The kinetics of the
      reduction reactions were successfully quantified using the Michaelis-Menten
      kinetic equation. Both the rates of Se(VI) and Se(IV) reduction displayed strong
      temperature-dependence with E(a) values of 121 and 71.2 kJ/ mol, respectively. X
      ray absorption near-edge spectra collected for the precipitates formed by Se(VI)
      and Se(IV) reduction confirmed the formation of Se(0). A miniTn5 transposon
      mutant of E. cloacae SLD1a-1 was isolated that had lost the ability to reduce
      Se(VI) but was not affected in Se(IV) reduction activity. Nucleotide sequence
      analysis revealed the transposon was inserted within a tatC gene, which encodes
      for a central protein in the twin arginine translocation system. Complementation
      by the wild-type tatC sequence restored the ability of mutant strains to reduce
      Se(VI). The results suggest that Se(VI) reduction activity is dependent on enzyme
      export across the cytoplasmic membrane and that reduction of Se(VI) and Se(IV)
      are catalyzed by different enzymatic systems.

PMID- 18075091
TI  - Carbon suboxide, a highly reactive intermediate from the abiotic degradation of
      aromatic compounds in soil.
AB  - The formation of volatile compounds during abiotic degradation processes of
      aromatic compounds in soil has been the subject of many experimental studies but
      should be examined further. In this context, the present work investigates the
      natural formation of carbon suboxide using the model compounds catechol and 3,5
      dichlorocatechol and also a soil sample from a peat bog. The measurements were
      performed with a purge and trap GC/ MS system following various optimization
      steps. Under certain conditions, we obtained 16.7 ng of carbon suboxide from a
      250 mg soil sample. We also found that the formation of carbon suboxide requires
      a definite activation energy and that it is rather short-lived in the natural
      environment. A subsequent reaction to malonic acid is expected in the presence of
      water. It is shown that iron-(III), hydrogen peroxide, and chloride are
      prerequisites for its formation. Experimental parameters for the highest yield of
      carbon suboxide depend on the precise molecular structure of the model compound
      or on the individual soil sample, respectively. The presented results point to a
      new degradation process for aromatic compounds in soil.

PMID- 18075092
TI  - The adjoint of CMAQ.
AB  - An adjoint model for the internationally used Community Multiscale Air Quality
      (CMAQ) modeling platform of the U.S. EPA is developed. The adjoint version for
      CMAQ (CMAQ-ADJ) provides the user community with forward (decoupled direct method
      or DDM) and backward (adjoint) sensitivity analysis capabilities. Current
      implementation is for gas-phase processes. Discrete adjoints are implemented for
      all processes with the exception of horizontal advection, for which, because of
      inherent discontinuities in the advection scheme, the continuous approach is
      superior. The adjoint of chemistry is constructed by interfacing CMAQ with the
      kinetic pre-processor, which provides for increased flexibility in the choice of
      chemical solver and facilitates the implementation of new chemical mechanisms.
      The adjoint implementation is evaluated both on a process-by-process basis and
      for the full model. In general, adjoint results show good agreement with brute
      force and DDM sensitivities. As expected for a continuous adjoint implementation
      in a nonlinear scheme, the agreement is not perfect for horizontal transport.
      Sensitivities of various air quality, public health, and environmental metrics
      with respect to emissions are calculated using the adjoint method. In order to
      show applicability to regional climate studies, as an example, the sensitivities
      of these metrics with respect to local temperatures are calculated.

PMID- 18075093
TI  - Improved approaches for modeling the sorption of phenanthrene by a range of plant
      species.
AB  - Equilibrium sorption of phenanthrene and its relationship with plant lipid
      contents were investigated using roots and shoots of alfalfa, ryegrass, tomato,
      potato, carrot, cucumber, zucchini, and pumpkin. Lipid extractions using
      chloroform and hexane were compared, and the influence of dechlorophyllization on
      lipid determinations was evaluated. The sorption isotherms were close to linear
      (R2 > 0.923, P < 0.05) and the plant-water partition coefficients (K(pl)) of
      phenanthrene obtained from the isotherms exhibited significant and positive
      correlations with plantlipid contents (R2 > 0.664, P < 0.05). The correlations
      were more significant (R2 > 0.906, P < 0.001) when dechlorophyllization was
      included in the lipid extraction. The measured sorption was higher than that
      estimated using the octanol-water partition coefficient (K(ow)) but was very
      close to the estimate using the triolein-water partition coefficient (K(tw)).
      This study leads us to conclude that dechlorophyllization is necessary for plant
      lipid determination and that K(tw) is more accurate as a substitute for the lipid
      water partition coefficient (K(lip)) than K(ow). These novel approaches may
      provide substantial improvements in the application of partition-limited models
      for the estimation of plant uptake of organic contaminants.

PMID- 18075094
TI  - Methoxyphenols and levoglucosan ratios in PM2.5 from wheat and Kentucky bluegrass
      stubble burning in eastern Washington and northern Idaho.
AB  - Eastern Washington is compromised by various pollution sources, of which
      agricultural burning is a particular burden. Smoke from field burning is a
      nuisance to nearby communities and is a concern for health. This study evaluates
      levoglucosan (LG) and methoxyphenols (MPs) as potential tracers for apportioning
      field burning smoke. PM2.5 (particulate matter < 2.5 microM m in aerodynamic
      diameter) samples from wheat and Kentucky bluegrass (KBG) stubble smoke were
      collected from chamber and field burns. The samples were analyzed for inorganic
      and organic tracers, including LG and 19 MPs. For the chamber experiments, the
      amount of LG, approximately 23 microg mg(-1) PM2.5, found in wheat and KBG
      stubble smoke was similar, while the total MPs was higher in wheat. Trace
      elements associated with soil were found in smoke samples in the field.
      Syringaldehyde, acetosyringone, and coniferylaldehyde were found to be the most
      prominent particle-phase MPs in wheat smoke, and these compounds were not always
      present in detectable amounts in KBG smoke. The ratio of LG/ syringaldehyde found
      in wheat (78 +/- 27) was higher than the same ratio reported for softwoods (22 +/
      3) and hardwoods (approximately 5). Similarly, the ratio of LG/coniferylaidehyde
      was higher in wheat stubble smoke (180 +/- 39) compared to that in softwoods
      (approximately 7) and hardwoods (approximately 8).

PMID- 18075095
TI  - Characterization of toxic effects of sediment-associated organic pollutants using
      the lambda transgenic medaka.
AB  - A novel sediment-contact assay using embryos of the transgenic medaka was
      developed to fully characterize the toxic effects induced by exposure to a
      mixture of organic pollutants in sediments. Embryos of the lambda transgenic
      medaka were exposed for 10 days to a clean reference sediment spiked with either
      the solvent alone, benzo[a]pyrene (B[a]P), or three concentrations (0.3x, 1x, and
      2x) of an organic extract (OE) of sediments from the Seine estuary. The 1 x OE
      spiked sediment contained concentrations of polycyclic aromatic hydrocarbons
      (PAHs) and polychlorinated biphenyls similar to those in field-collected
      sediment. Exposure to this sediment, but not to the B[a]P-spiked sediment,
      significantly increased embryo-larval mortality and prevalence of spinal
      deformities. Mutant frequency at the cII mutation target gene in the liver of 10
      week-old medaka was significantly increased following exposure to either B[a]P or
      the three doses of OE. The predominant OE-induced liver mutations were G:C to T:A
      transversions, consistent with PAHs being the major contributors to the mutation
      induction. Liver and gonadal tumors were observed in 35-week-old medaka exposed
      to either B[a]P (1/25) or to the 1 x OE (1/24). The benefits of medaka as a fish
      model for toxicological assessment and the benefits of the cII mutation assay for
      mutation detection combine to provide comprehensive assessment of a wide range of
      genotoxic and nongenotoxic effects of aquatic pollutants.

PMID- 18075096
TI  - Measuring simultaneous production and consumption fluxes of methyl chloride and
      methyl bromide in annual temperate grasslands.
AB  - Methyl chloride (CH3Cl) and methyl bromide (CH3Br) are both produced and consumed
      by terrestrial ecosystems, but large uncertainties remain about the magnitude of
      their emission and uptake rates. Most field-based studies report net fluxes, but
      knowledge of gross fluxes is required to assess partial atmospheric lifetimes and
      potential mechanisms. Here, we present the first field results using a stable
      isotope tracer technique to determine gross emission and uptake fluxes of CH3Cl
      and CH3Br at two temperate annual grasslands in California. These grasslands
      generally showed modest emission and uptake rates of CH3Cl and CH3Br, although
      large net emissions were observed at riparian and dry playa sites within these
      grasslands. While gross production rates of the methyl halides are not correlated
      to each other, gross consumption rates of CH3Cl and CH3Br show a molar uptake
      ratio of approximately 40: 1, consistent with results from other biomes. Gross
      consumption rates appear to be strongly affected by soil moisture. Temperate
      grassland soils have been previously identified as a globally significant sink
      for CH3Br, accounting for approximately 25% of the total soil sink, but our
      results suggest that the uptake rate could be much smaller.

PMID- 18075097
TI  - Characterization and quantification of reversible redox sites in humic
      substances.
AB  - Cyclic oxidation and reduction reactions using oxygen and palladium with H2,
      respectively, of dissolved humic and fulvic acids (HA and FA) and model quinone
      compounds were used to structurally characterize and quantify the electron
      carrying capacity (ECC) of reversible redox sites present in humic substances.
      This technique was used to examine 8 quinone compounds and 14 HA and FA samples
      and identified 3 redox sites as a function of their stability against the Pd
      catalyzed hydrogenolysis process. Six highly aliphatic HA and FA isolated from
      landfill leachate did not contain redox sites under any conditions; however, the
      other HA and FA demonstrated reversible redox properties characterized by a
      combination of three redox sites. On the basis of the model compound results, it
      is proposed that one site consists of a non-quinone structure (NQ) and the other
      two sites have quinone structures. The two quinone sites differ in that one group
      (Q1) has electron-withdrawing groups adjacent to the quinone functional group
      while the second group (Q2) contains either no substituents near the quinone or
      has nearby electron-donating groups with additional substitutents hindering
      hydrogenolysis through steric interactions. The reversible ECC of NQ sites ranged
      from 25 to 265 microequiv e- transferred/g HA or FA, representing 21-56% of the
      total ECC of the HA and FA when measured with the mildest reducing method (pH
      8.0, pure Pd). Q1 redox sites resistant to hydrogenolysis at pH 8.0 using
      Pd/Al2O3 accounted for 13-58% of the total ECC and ranged from 40 to 120
      microequiv e-/ g HA or FA. The most sensitive O2 reversible redox sites accounted
      for 8-50% of the total ECC (20-220 microequiv e-/ g HA or FA). These results
      directly demonstrate that HA and FA are capable of acting as reversible electron
      transfer agents using different functional groups, some of which may not be
      quinones.

PMID- 18075098
TI  - Bioaccessibility of metals in dust from the indoor environment: application of a
      physiologically based extraction test.
AB  - A physiologically based extraction test, simulating sequential digestion in the
      stomach and intestine, has been applied to dust samples collected from various
      domestic and working settings to define bioaccessible concentrations of metals
      (Al, Ca, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sn, U, Zn) in the indoor environment.
      With the exception of Ca, Cd, and Zn in the stomach phase, mean
      bioaccessibilities (relative to respective total metal concentrations) were less
      than 50%. For a given metal, bioaccessibility in either phase was variable among
      samples but, in many cases, displayed an inverse dependence on total
      concentration. This suggests that, to a good approximation, variations in both
      metal contamination and accessibility in the indoor environment arise from
      variable proportions of metal-rich particulates of low digestibility. Compared
      with accessibility in the stomach, accessibility in the more alkaline, carbonate
      rich intestine was either lower (Al, Ca, Cd, Mn, Ni, Sn, Pb, Zn), similar (Co,
      Cu, Fe) or greater (Cr, U). We attribute these observations to precipitation
      and/or readsorption in the intestine, stabilization by complexation, or anion
      like adsorption of negatively charged, polyatomic species, respectively.

PMID- 18075099
TI  - MEMS needle-type sensor array for in situ measurements of dissolved oxygen and
      redox potential.
AB  - Microelectrodes are among the most accurate and reliable monitoring devices for
      measuring the dynamics of biofilm processes. This paper describes a novel needle
      type microelectrode array (MEA) for simultaneous in situ measurements of
      dissolved oxygen (DO) and oxidation reduction potential (ORP) fabricated using
      microelectromechanical systems (MEMS) technologies. The MEA exhibits fast
      response times for both DO and ORP measurements and shows a substantial increase
      in DO sensitivity. To demonstrate the versatility of the new sensor, it was
      applied to the measurement of DO and ORP microprofiles in a multispecies biofilm.
      This work demonstrates that the MEA is able to monitor local concentration
      changes with a high spatial resolution and provide the versatility of the
      microelectrode technique needed for biofilm studies as well as the capability for
      repetitive measurements. In addition, the use of MEMS technologies and batch
      fabrication approaches enables integration, high consistency, high yields, and
      mass production. With further development, it may be possible to add additional
      sensors to the MEA (e.g., pH, phosphate) and integrate them with a reference
      electrode.

PMID- 18075100
TI  - Spectromicroscopy mapping of colloidal/particulate organic matter in Lake Brienz,
      Switzerland.
AB  - Transmission electron microscopy (TEM), soft X-ray scanning transmission X-ray
      microscopy (STXM), and mu-FTIR spectromicroscopy were used to map colloidal/
      particulate material in an ultra-oligotrophic lake, Lake Brienz, Switzerland,
      with a special focus on organic functionality. Within the statistical margin of
      error and the uncertainties arising from the representativeness of the results,
      the research reveals that organic material was associated with potassium-rich
      inorganic colloids present in surface and deep water (depths of 1 and 100 m,
      respectively), which indicates a vertical transfer of aggregates by
      sedimentation. Pure organic colloids could only be detected in surface waters. In
      addition, correlation map analysis of synchrotron-based mu-FTIR and carbon K-edge
      STXM spectromicroscopic data using spectra from the Lutschine and Aare Rivers as
      target spectra revealed spectral similarities with organic components from both
      tributary rivers in deeper regions (100 m) of the lake. The results prove that
      STXM and mu-FTIR can characterize colloidal and particulate organic material in
      low organic carbon systems.

PMID- 18075101
TI  - Understanding mercury transformations in coal-fired power plants: evaluation of
      homogeneous Hg oxidation mechanisms.
AB  - Homogeneous mercury oxidation mechanisms described by Niksa and Qiu, and three
      theoretical mercury oxidation reaction rate constants developed by Wilcox were
      evaluated for their predictions of the extent of mercury oxidation under coal
      combustion conditions. Predictions were compared to results from bench-scale
      experiments to determine whether such models were suitable for predicting
      measured levels of homogeneous mercury oxidation. Experiments considered
      different flue gas compositions (O2, Cl, NO, and SO2) and quench rates to provide
      a broad range of conditions for analysis. Regardless of the mechanism chosen,
      most mercury oxidation was predicted to occur at temperatures below 900 K. The
      Niksa mechanism predicted Hg oxidation to occur only in systems that were close
      to isothermal at temperatures above 900 K followed by a rapid gas quench. This
      mechanism provided the best agreement with the experimental data of Sliger. The
      Qiu mechanism predicted Hg oxidation in several experimental systems and
      conditions fairly accurately although it did not provide the best agreement in
      all cases. Qiu mechanism predictions for the experimental system at the
      University of Connecticut operating at an equivalence ratio of 0.9 in the
      presence of HCl/Cl2 and also SO2 were within the bounds of experimental
      uncertainty. Additionally, for an experimental dataset obtained from the
      University of Utah for quench rates of 210 and 440 K/s in the presence of HCI,
      the Qiu model predicted the experimental observations with a high degree of
      accuracy. The effects of flue gas composition and quench on Hg oxidation are
      qualitatively represented by the Qiu mechanism suggesting a relative robustness
      of the model, although there is still need to refine rate constants to achieve
      greater accuracy. The Wilcox rate constants when substituted in the Qiu mechanism
      predicted near-complete oxidation of Hg irrespective of HCl concentrations in
      systems that involve flue gas quench below temperatures of 450 K.

PMID- 18075102
TI  - Solid-state, planar photoelectrocatalytic devices using a nanosized TiO2 layer.
AB  - Solid-state planar photoelectrocatalytic devices using a nanosized Ti02 layer
      have been fabricated and used in the photodegradation of gaseous formaldehyde
      (HCHO). It is discovered for the first time that in the photocatalytic
      degradation of HCHO over TiO2 film, besides a well-known process of exciton
      dissociation expressed as TiO2* --> e(-) + h+ (process A), there exists an HCHO
      involved process of exciton dissociation expressed as TiO2 + HCHO* --> TiO2(-) +
      HCHO+ (process B); these two processes have comparable contributions to the
      electron photogeneration. A biased photocatalytic device is unable to
      photodegrade HCHO under the nitrogen condition, but under the air condition, a
      positive synergic effect of bias on the photodegradation of HCHO over the planar
      photoelectrocatalytic device has been observed, mainly attributed to it that the
      horizontal electric field can displace electrons generated via process B away
      from their counterparts, effectively suppressing hole-electron recombination on
      TiO2 surface and thereby leading to the enhanced formation of O2- species. The
      current research points out that the planar photoelectrocatalytic device can
      provide the in-depth investigations on the mechanisms of the photocatalytic
      degradation over nanosized semiconductor oxide films, and also have potential
      application in decomposing and mineralizing organic gas-phase pollutants.

PMID- 18075103
TI  - Effect of TCE concentration and dissolved groundwater solutes on NZVI-promoted
      TCE dechlorination and H2 evolution.
AB  - Nanoscale zero-valent iron (NZVI) is used to remediate contaminated groundwater
      plumes and contaminant source zones. The target contaminant concentration and
      groundwater solutes (NO3-, Cl-, HCO3-, SO4(2-), and HPO4(2-)) should affect the
      NZVI longevity and reactivity with target contaminants, but these effects are not
      well understood. This study evaluates the effect of trichloroethylene (TCE)
      concentration and common dissolved groundwater solutes on the rates of NZVI
      promoted TCE dechlorination and H2 evolution in batch reactors. Both model
      systems and real groundwater are evaluated. The TCE reaction rate constant was
      unaffected by TCE concentration for [TCE] < or = 0.46 mM and decreased by less
      than a factor of 2 for further increases in TCE concentration up to water
      saturation (8.4 mM). For [TCE] > or = 0.46 mM, acetylene formation increased, and
      the total amount of H2 evolved at the end of the particle reactive lifetime
      decreased with increasing [TCE], indicating a higher Fe0 utilization efficiency
      for TCE dechlorination. Common groundwater anions (5mN) had a minor effect on H2
      evolution but inhibited TCE reduction up to 7-fold in increasing order of Cl- <
      SO4(2-) < HCO3- < HPO4(2). This order is consistent with their affinity to form
      complexes with iron oxide. Nitrate, a NZVI-reducible groundwater solute, present
      at 0.2 and 1 mN did not affect the rate of TCE reduction but increased acetylene
      production and decreased H2 evolution. NO3- present at > 3 mM slowed TCE
      dechlorination due to surface passivation. NO3- present at 5 mM stopped TCE
      dechlorination and H2 evolution after 3 days. Dissolved solutes accounted for the
      observed decrease of NZVI reactivity for TCE dechlorination in natural
      groundwater when the total organic content was small (< 1 mg/L).

PMID- 18075104
TI  - Approaches to mitigate the impact of dissolved organic matter on the adsorption
      of synthetic organic contaminants by porous carbonaceous sorbents.
AB  - Adsorption of trichloroethylene (TCE) and atrazine, two synthetic organic
      contaminants (SOCs) having different optimum adsorption pore regions, by four
      activated carbons and an activated carbon fiber (ACF) was examined. The selected
      adsorbents had a wide range of pore size distributions but similar surface
      acidity and hydrophobicity. Single solute and preloading (with a dissolved
      organic matter (DOM)) isotherms were performed. Single solute adsorption results
      showed that (i) the adsorbents having higher amounts of pores with sizes about
      the dimensions of the adsorbate molecules exhibited higher uptakes, (ii) there
      were some pore structure characteristics, which were not completely captured by
      pore size distribution analysis, that also affected the adsorption, and (iii) the
      BET surface area and total pore volume were not the primary factors controlling
      the adsorption of SOCs. The preloading isotherm results showed that for TCE
      adsorbing primarily in pores < 10 angstroms, the highly microporous ACF and GACs,
      acting like molecular sieves, exhibited the highest uptakes. For atrazine with an
      optimum adsorption pore region of 10-20 angstroms, which overlaps with the
      adsorption region of some DOM components, the GACs with a broad pore size
      distribution and high pore volumes in the 10-20 angstroms region had the least
      impact of DOM on the adsorption.

PMID- 18075105
TI  - Enhanced power from chambered benthic microbial fuel cells.
AB  - We describe a new chamber-based benthic microbial fuel cell (BMFC) that
      incorporates a suspended, high surface area and semi-enclosed anode to improve
      performance. In Yaquina Bay, OR, two chambered BMFC prototypes generated current
      continuously for over 200 days. One BMFC was pumped intermittently, which
      produced power densities more than an order of magnitude greater than those
      achieved by previous BMFCs with single buried graphite-plate anodes. On average,
      the continuous power densities with pumping were 233 mW/m2 (2.3 W/m3); peak
      values were 380 mW/m2 (3.8 W/m3), and performance improved over the time of the
      deployments. Without pumping, high power densities could similarly be achieved
      after either BMFC was allowed to rest at open circuit. A third chambered BMFC
      with a 0.4 m2 footprint was deployed at a cold seep in Monterey Canyon, CA to
      test the new design in an environment with natural advection. The power density
      increased 5-fold (140 mW/m2 vs 28 mW/m2) when low-pressure check valves allowed
      unidirectional flow through the chamber.

PMID- 18075106
TI  - Fe-USY zeolite catalyst for effective decomposition of nitrous oxide.
AB  - Zeolite matrix FAU is applied as an effective support that can be readily
      exchanged with ferric ions simply by wet ion exchange. The high exchange degree
      in this zeolite (USY) probably benefits from its larger channel dimension, which
      makes the diffusion of hydrated ferric ions into the channels easier. The as
      prepared and subsequently calcined Fe-USY samples contain various kinds of iron
      species, which enable Fe-USY to efficiently decompose N2O to N2 and O2. The
      presence of O2 (20%), H2O (2%), or both reduces the N2O conversion only to a
      small extent at the same temperature. To test the feasibility and the catalytic
      activity in a practical situation, we prepared a monolithic Fe-USY/cordierite
      sample and investigated the N2O conversion under similar conditions. Such a
      cordierite-supported Fe-USY catalyst (approximately 9 wt % USY and 0.5 wt % Fe)
      shows the catalytic performance in N20 decomposition similar to the pure Fe-USY
      catalyst. Remarkably, both the pure Fe-USY and Fe-USY/cordierite catalysts
      demonstrate a very good durability because there is no activity lost after 100
      and 144 h tests. Thus, the Fe-USY zeolite shows its potential as a cost-effective
      catalyst for N2O elimination in future applications.

PMID- 18075107
TI  - Photocatalytic reduction of Cr(VI) in the presence of NO3- and Cl- electrolytes
      as influenced by Fe(III).
AB  - Photoreduction of Cr(VI) involving Fe is strongly affected by the presence of
      organic or inorganic compounds in an acidic environment. In this study, we have
      found a new pathway of Cr(VI) photoreduction in the presence of Fe-(III) that is
      influenced by two inorganic electrolytes (i.e., NO3- and Cl-) and the pH. In NO3-
      and Cl- systems without Fe(III), Cr(VI) photoreduction could occur and was
      independent of the Cr(VI) concentration. The zero-order rate constant of the
      photoreduction reaction increased when the solution pH was decreased from 2 to 1;
      the reaction rate was higher in the NO3- system than in the Cl- system. The
      higher reaction rate in the NO3- system was attributed to the photolysis of NO3-,
      which resulted in the formation of NO2- for reduction of Cr(VI). Conversely, the
      effect of Fe-(III) addition on the increase in Cr(VI) photoreduction rate in the
      Cl- system was more significant than that in the NO3- system. The addition of
      Fe(III) to the Cl- system caused the formation of [Fe(OH2)5Cl]2+, the photolysis
      of which subsequently resulted in the formation of Fe(II) for reduction of the
      Cr(VI). This study suggests that the photolysis of NO3- and Fe-Cl complex may
      contribute significantly to Cr(VI) reduction in surface water that receives
      electroplating wastewater containing high levels of NO3-, Cl-, and Fe-(III).
      Therefore, under the acidic conditions that are favorable for Fe-Cl complex
      formation or in the presence of NO3-, the effects of inorganic components on
      Cr(VI) photoreduction cannot be ignored for the precise evaluation of the
      transformation of Cr in the environment.

PMID- 18075108
TI  - Producing bio-based bulk chemicals using industrial biotechnology saves energy
      and combats climate change.
AB  - The production of bulk chemicals from biomass can make a significant contribution
      to solving two of the most urgent environmental problems: climate change and
      depletion of fossil energy. We analyzed current and future technology routes
      leading to 15 bulk chemicals using industrial biotechnology and calculated their
      CO2 emissions and fossil energy use. Savings of more than 100% in non-renewable
      energy use and greenhouse gas emissions are already possible with current state
      of the art biotechnology. Substantial further savings are possible for the future
      by improved fermentation and downstream processing. Worldwide CO2 savings in the
      range of 500-1000 million tons per year are possible using future technology.
      Industrial biotechnology hence offers excellent opportunities for mitigating
      greenhouse gas emissions and decreasing dependence on fossil energy sources and
      therefore has the potential to make inroads into the existing chemical industry.

PMID- 18075109
TI  - Characterization of hydrocarbon emissions from green sand foundry core binders by
      analytical pyrolysis.
AB  - Analytical pyrolysis was conducted to study a relative comparison of the
      hydrocarbon and greenhouse gas emissions of three foundry sand binders as
      follows: (a) conventional phenolic urethane resin, (b) biodiesel phenolic
      urethane resin, and (c) collagen-based binder. These binders are used in the
      metal casting industry for making cores that are used to create internal cavities
      within castings. In this study, the core samples were flash pyrolyzed in a Curie
      point pyrolyzer at 920 degrees C with a heating rate of about 3000 degrees C/sec.
      This simulated some key features of the fast heating conditions that the core
      binders would experience at the metal-core interface when molten metal is poured
      into green sand molds. The core samples were also pyrolyzed in a
      thermogravimetric analyzer (TGA) from ambient temperature to 1000 degrees C with
      a heating rate of 30 degrees C/min, and this simulated key features of the slow
      heating conditions that the core binders would experience at distances that are
      further away from the metal-core interface during casting cooling. Hydrocarbon
      emissions from flash pyrolysis were analyzed with a gas chromatography-flame
      ionization detector, while hydrocarbon and greenhouse gas (CO and CO2) emissions
      from TGA pyrolysis were monitored with mass spectrometry. The prominent hazardous
      air pollutant emissions during pyrolysis of the three binders were phenol,
      cresols, benzene, and toluene for the conventional phenolic urethane resin and
      biodiesel resin, and they were benzene and toluene for the collagen-based binder.
      It was also found that volatile organic compound and polycyclic aromatic
      hydrocarbon emissions considerably decreased in order from conventional phenolic
      urethane resin to biodiesel resin to collagen-based binder. These results have
      shown some similarity with those for stack emission testing conducted at
      demonstration scale and/or full-scale foundries, and the similar trends in the
      two sets of results offered promise that bench-scale analytical pyrolysis
      techniques could be a useful screening tool for the foundries to compare the
      relative emissions of alternative core binders and to choose proper materials in
      order to comply with air-emission regulations.

PMID- 18075110
TI  - Exposure of an adult population to perfluorinated substances using duplicate diet
      portions and biomonitoring data.
AB  - Because dietary intake is supposed to be an important route of human exposure we
      quantified the dietary intake of perfluorooctane sulfonate (PFOS),
      perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), perfluorohexanoate
      (PFHxA), and perfluorooctane sulfonamide (PFOSA) using 214 duplicate diet
      samples. The study was carried out with a study population of 15 female and 16
      male healthy subjects aged 16-45 years. The participants collected daily
      duplicate diet samples over seven consecutive days in 2005. Duplicate samples
      were homogenized and their ultrasonic extracts were cleaned up by SPE and
      subjected to HPLC-ESI-MS/MS. In addition, individual intakes were estimated based
      on blood levels of PFOS and PFOA using a pharmacokinetic model. Blood samples
      were collected once during the sampling period. The median (90th percentile)
      daily dietary intake of PFOS and PFOA was 1.4 ng/kg b.w. (3.8 ng/kg b.w.) and 2.9
      ng/kg b.w. (8.4 ng/kg b.w.), respectively. PFHxS and PFHxA could be detected only
      in some samples above detection limit with median (maximum) daily intakes of 2.0
      ng/kg b.w. (4.0 ng/kg b.w.) and 4.3 ng/kg b.w. (9.2 ng/kg b.w.), respectively.
      Because PFOSA could not be detected above the limit of detection of 0.2 ng/g f.w.
      this indirect route of exposure seems to be of less significance. Overall, the
      results of this study demonstrate that the German population is exposed to PFOS
      and PFOA, but the median dietary intake did not reach the recommended tolerable
      daily intake by far. Biomonitoring data predict an exposure in a comparable
      range. We suppose that, normally, food intake is the main source of exposure of
      the general population to PFOS and PFOA.

PMID- 18075111
TI  - Controlled exposure chamber study of uptake and clearance of airborne polycyclic
      aromatic hydrocarbons by wheat grain.
AB  - Polycyclic aromatic hydrocarbons (PAHs) can partition from the atmosphere into
      agricultural crops, contributing to exposure through the dietary pathway. In this
      study, controlled environmental chamber experiments were conducted to investigate
      the transfer of PAHs from air into wheat grain, which is a major food staple. A
      series of PAHs ranging in size from naphthalene to pyrene were maintained at
      elevated gas-phase concentrations in the chamber housing mature and dry wheat
      grain both on the plant and with the husk removed. The PAHs did not achieve
      equilibrium between the air and grain over the 6.5 month monitoring period used
      in this study. Therefore, PAH uptake under field conditions is expected to be
      kinetically limited. A clearance study conducted for the grain showed the half
      life of clearance was approximately 20 days for all compounds studied. The
      results suggest that atmospheric contaminants that partition into grain may
      remain in the grain long enough to contribute to dietary exposure for humans.
      Mass transfer across the air/grain interface appeared to be limited by grain-side
      resistance. The grain may act as a multicompartment system with rapid exchange at
      the surface followed by slower transfer into the grain. A grain/air concentration
      relationship was derived for the uptake time that is relevant to field
      conditions.

PMID- 18075112
TI  - Combined cadmium and thiuram show synergistic toxicity and induce mitochondrial
      petite mutants.
AB  - A bioassay is a system for monitoring toxicity of chemicals in the environment
      via the biological responses of experimental organisms. These responses can be
      detected by analysis of genome-wide changes in mRNA expression levels using DNA
      microarrays. We applied this system for evaluation of synergistic toxicity by
      cadmium and thiuram, as this combination showed mutual growth inhibition in
      yeast. Hierarchical cluster analysis using mRNA expression profiles suggested the
      response of yeast to this combination is similar to that seen with cadmium
      treatment alone. Functional characterization of genes induced by this
      combinational treatment also suggests that the toxicity of cadmium was enhanced.
      This toxicity was observed as the damage to mitochondrial functions, which were
      not observed with either cadmium or thiuram treatments alone. The potential
      toxicity to mitochondria by this combinational treatment was confirmed as the
      result of deletion of mitochondria with petite colony formation frequency. We
      could evaluate synergistic toxicity by cadmium and thiuram and show the possible
      use of transcriptome bioassay for synergistic toxicity.

PMID- 18075113
TI  - Comment on "1,1,2,2-Tetrachloroethane reactions with OH-, Cr(II), granular iron,
      and a copper-iron bimetal: insights from product formation and associated carbon
      isotope fractionation".

PMID- 18075114
TI  - A short and personal story of Suzanne Tyc-Dumont in the scientific context of the
      time.

PMID- 18075115
TI  - Functional diversity of motoneuron dendrites: by accident or design?
AB  - The distribution and geometry of the dendritic trees of spinal motoneurons obey
      several well-established rules. Some of these rules are based on systematic
      relationships between quantitative geometrical features (e.g. total dendritic
      length) and the three-dimensional trajectory followed by dendrites from their
      origin to their termination. Since dendritic geometry partially determines the
      transmission of current and voltage signals generated by synapses on the
      dendritic tree, our goal was to compare the efficacy of signal transmission by
      dendritic trajectories that followed different directions. To achieve this goal,
      we constructed detailed compartmental models of the dendritic trees of
      intracellularly stained neck motoneurons and calculated the electrotonic
      properties of each soma-to-terminal trajectory. These properties displayed a high
      degree of variability. To determine if this variability was due, in part, to the
      orientation (e.g. rostral, rostral-dorsal-lateral) of the trajectory, each
      trajectory was classified according to its orientation. The attenuation of
      current and voltage signals en route to the soma were strongly related to
      trajectory orientation. Trajectories with similar attenuation factors formed
      functional subunits that were arranged in distinct domains within the ventral
      horn. The difference in the efficacy of signal transmission between subunits was
      increased by activation of neighbouring synapses due to trajectory-related
      differences in non-linear summation. These results indicate that the input-output
      properties of motoneurons depend on the direction of the path taken by dendrites
      from their origin at the cell body to their terminals.

PMID- 18075116
TI  - Real-time closed-loop electrophysiology: towards new frontiers in in vitro
      investigations in the neurosciences.
AB  - Reflected at any level of organization of the central nervous system, most of the
      processes ranging from ion channels to neuronal networks occur in a closed loop,
      where the input to the system depends on its output. In contrast, most in vitro
      preparations and experimental protocols operate autonomously, and do not depend
      on the output of the studied system. Thanks to the progress in digital signal
      processing and real-time computing, it is now possible to artificially close the
      loop and investigate biophysical processes and mechanisms under increased
      realism. In this contribution, we review some of the most relevant examples of a
      new trend in in vitro electrophysiology, ranging from the use of dynamic-clamp to
      multi-electrode distributed feedback stimulation. We are convinced these
      represents the beginning of new frontiers for the in vitro investigation of the
      brain, promising to open the still existing borders between theoretical and
      experimental approaches while taking advantage of cutting edge technologies.

PMID- 18075117
TI  - The electro-dynamics of the dendritic space in Purkinje cells of the cerebellum.
AB  - The functional geometry of the reconstructed dendritic arborization of Purkinje
      neurons is the object of this work. The combined effects of the local geometry of
      the dendritic branches and of the membrane mechanisms are computed in passive
      configuration to obtain the electrotonic structure of the arborization. Steady
      currents applied to the soma and expressed as a function of the path distance
      from the soma form different clusters of profiles in which dendritic branches are
      similar in voltages and current transfer effectiveness. The locations of the
      different clusters are mapped on the dendrograms and 3D representations of the
      arborization. It reveals the presence of different spatial dendritic sectors
      clearly separated in 3D space that shape the arborization in ordered electrical
      domains, each with similar passive charge transfer efficiencies. Further
      simulations are performed in active configuration with a realistic cocktail of
      conductances to find out whether similar spatial domains found in the passive
      model also characterize the active dendritic arborization. During tonic
      activation of excitatory synaptic inputs homogeneously distributed over the whole
      arborization, the Purkinje cell generates regular oscillatory potentials. The
      temporal patterns of the electrical oscillations induce similar spatial sectors
      in the arborization as those observed in the passive electrotonic structure. By
      taking a video of the dendritic maps of the membrane potentials during a single
      oscillation, we demonstrate that the functional dendritic field of a Purkinje
      neuron displays dynamic changes which occur in the spatial distribution of
      membrane potentials in the course of the oscillation. We conclude that the
      branching pattern of the arborization explains such continuous reconfiguration
      and discuss its functional implications.

PMID- 18075118
TI  - On coupling and decoupling of spinal interneuronal networks.
AB  - This review addresses the question of interrelations between spinal interneuronal
      networks. On the basis of electrophysiological, pharmacological, morphological
      and immunohistochemical analysis of interneurones mediating various reflex
      actions from muscle receptors and of reticulospinal neurones a considerable
      degree of interweaving between networks of these neurones has been established.
      The coupling has been found to occur at the level of several sites of these
      networks but the review focuses on two of these sites. The first is between
      dorsal horn interneurones with group II input and their target ipsilaterally and
      contralaterally projecting intermediate zone and commissural interneurones. The
      second is between commissural interneurones with input from reticulospinal
      neurones and their target interneurones. Several ways of both strengthening and
      weakening of coupling between various interneuronal networks are also briefly
      reviewed.

PMID- 18075119
TI  - Input-output transformation in the visuo-oculomotor loop: comparison of real-time
      optical imaging recordings in V1 to ocular following responses upon center
      surround stimulation.
AB  - In psychophysics and physiology, it is well established that lateral interactions
      are crucial mechanisms to constrain response normalization and contextual
      modulations. To study the cortical mechanisms involved in the contextual
      modulation of the behavioral contrast response function, we compared in behaving
      monkeys the Ocular Following Response (OFR) to V1 population activity measured
      using Optical Imaging of Voltage-Sensitive Dyes (VSD). If contrast response
      functions (CRF) to a simple local stimulus are similar in V1 and in the OFR,
      lateral interaction leads however to quite different modulation at those two
      levels. At the behavioural level, contrast response function is strongly
      suppressed by lateral interactions, and this suppression is stronger for higher
      contrasts. In V1, we showed a slow dynamic of facilitation for low contrasts
      integration and a fast suppression operating on high contrasts. These modulatory
      interactions influence differently the contrast response functions, interrupting
      the dynamic increase of contrast sensitivity in OFR, but not in V1 response. The
      temporal properties of those effects lead us to hypothesize that horizontal and
      feedback connectivity have differential effect on low and high contrasts
      integration in V1. V1 provides then an input to MT whose contextual dependency is
      not totally determined and must be refined before affecting the behavioural OFR.

PMID- 18075120
TI  - The locust olfactory system as a case study for modeling dynamics of
      neurobiological networks: from discrete time neurons to continuous time neurons.
AB  - Both chaotic and periodic activities are observed in networks of the central
      nervous systems. We choose the locust olfactory system as a good case study to
      analyze the relationships between networks' structure and the types of dynamics
      involved in coding mechanisms. In our modeling approach, we first build a fully
      connected recurrent network of synchronously updated McCulloch and Pitts neurons
      (MC-P type). In order to measure the use of the temporal dimension in the complex
      spatio-temporal patterns produced by the networks, we have defined an index the
      Normalized Euclidian Distance NED. We find that for appropriate parameters of
      input and connectivity, when adding some strong connections to the initial random
      synaptic matrices, it was easy to get the emergence of both robust oscillations
      and distributed synchrony in the spatiotemporal patterns. Then, in order to
      validate the MC-P model as a tool for analysis for network properties, we examine
      the dynamic behavior of networks of continuous time model neuron (Izhikevitch
      Integrate and Fire model -IFI-), implementing the same network characteristics.
      In both models, similarly to biological PN, the activity of excitatory neurons
      are phase-locked to different cycles of oscillations which remind the ones of the
      local field potential (LFP), and nevertheless exhibit dynamic behavior complex
      enough to be the basis of spatio-temporal codes.

PMID- 18075121
TI  - Plasticity of neuronal excitability: Hebbian rules beyond the synapse.
AB  - Activity-dependent synaptic plasticity is classically though to be the cellular
      substrate for learning and memory. Recent data show that activation of glutamate
      receptors initiates a long-term modification in pre- or post-synaptic neuronal
      excitability. Similarly to synaptic plasticity, intrinsic plasticity is
      bidirectional and input- or cell-specific. In addition to an increase in the
      reliability of the input-output function, temporal precision of the neuronal
      discharge is improved. These forms of plasticity not only share common learning
      rules and induction pathways with the better known synaptic plasticity but may
      also contribute in synergy with these synaptic changes to the formation of a
      coherent mnesic engram.

PMID- 18075122
TI  - MEA-based recording of neuronal activity in vitro.
AB  - Based on the advantages of MEA-based recording, developmental changes of
      spontaneous activity and tetanus-induced modification of evoked activity were
      studied. Rat cortical neurons were cultured on MEAs and the spontaneous activity
      was continuously monitored for two months. The activity started a few days after
      plating. During the second week, the cultures generated periodic synchronized
      bursts, which were the characteristic properties of cortical neurons in vitro. In
      about one month, the cultured networks reached a steady state. Between these two,
      we found a critical period during which only weak activities were generated. This
      critical period might reflect the transition from immature networks to mature
      networks including precisely controlled excitatory and inhibitory synapses. We
      could elicit clear evoked responses with high reproducibility in mature cultures.
      A focal tetanic stimulation was applied to the mature cultures and how the
      tetanus affects 64 kinds of evoked activity was studied. The evoked responses
      showed bi-directional changes in their propagation patterns, potentiation and
      depression. These induced changes reflected the correlation properties with the
      tetanized activity pattern. The next step will be the combination of long-term
      recording and multi-site stimulation. How long does the induced change last, as
      well as how additional strong activity affects the previously induced changes,
      will be studied.

PMID- 18075123
TI  - A computational approach to the study of AMPA receptor clustering at Purkinje
      cell synapses.
AB  - Synapses between parallel fibres and Purkinje cells in the cerebellum exhibit
      unique forms of synaptic plasticity thought to be associated with the refinement
      of motor skills. Since the discovery of Long Term Depression (LTD), more than
      twenty years ago, many molecular signalling pathways potentially underlying LTD
      have been explored. These have revealed a surprisingly diverse array of cellular
      and molecular mechanisms. Foremost has been the now well-established discovery
      that LTD is the electrophysiological manifestation of a reduced density of AMPA
      receptors at the synapse, following induction. Although LTD is primarily an
      electrophysiologically defined phenomenon, recent studies have increasingly
      combined electrophysiological, imaging, proteomic and biochemical approaches to
      probe its mechanisms. The challenge is now to integrate data from different
      modalities into a unified formalism that can deal with the complexity of the
      system, as well as generate experimental predictions. Here, we use particle-based
      stochastic modelling as a prototype to explore the feasibility of building
      realistic model of synaptic plasticity, at the molecular level.

PMID- 18075125
TI  - Understanding motoneurone development explains spinal muscular atrophy.

PMID- 18075124
TI  - Postnatal electrical and morphological abnormalities in lumbar motoneurons from
      transgenic mouse models of amyotrophic lateral sclerosis.
AB  - Antidromically identified lumbar motoneurons intracellularly recorded in the
      entire brainstem/spinal cord preparation isolated from SOD1(G85R) postnatal mice
      (P3-P10) were labelled with neurobiotin and fully reconstructed in 3D from serial
      sections in order to analyse their morphology. This staining procedure revealed
      differences between WT and SOD1(G85R) dendritic trees for most metric and
      topologic parameters analyzed. A highly complex morphology of SOD1(G85R)
      motoneurons dendrites (increased number of branching points and terminations) was
      found and the dendritic trees were longer compared to the WT motoneurons. These
      morphological changes observed in P8-P9 motoneurons mice occurred concomitantly
      with a decrease in the input resistance and gain. During electrophysiological
      recordings, four patterns of discharge were observed in response to ramp
      stimulations, that were equally distributed in WT and SOD1(G85R) motoneurons. In
      slice preparation, whole cell patch-clamp recordings made from developing
      motoneurons in SOD1(G85R) and double transgenic SOD1(G93A)/Hb9-eGFP mice showed
      that Riluzole, a blocker of persistent inward sodium conductance, altered the
      repetitive firing in a similar way for the 2 strains. These results show that the
      SOD1 mutations linked to familial ALS alter the development of the electrical and
      morphological properties of lumbar motoneurons.

PMID- 18075126
TI  - Modification of motoneuron size after partial denervation in neonatal rats.
AB  - Our previous studies have shown that partial denervation of extensor digitorum
      longus muscle (EDL) in the rat at 3 days of age causes an increase in the
      activity of the intact motoneurons. The originally phasic pattern of activity of
      EDL became tonic after partial denervation. These modifications of motoneuron
      activity were associated with the change in the phenotype of the muscle from fast
      to slow contracting and with a conversion of the muscle fibres from a fast to a
      slow type. The present study investigates whether the size of the cell body of
      the active EDL motoneurons change in parallel with the altered muscular activity.
      The study involved partial denervation of rat EDL muscle by section of the L4
      spinal nerve at 3 days of age. Then the remaining motoneurons from L5 spinal
      nerve supplying the EDL muscle were retrogradly labelled with horseradish
      peroxidase two months later. The results show a reduction in motoneuron size in
      parallel with an increase in activity of the motoneurons after partial
      denervation of EDL muscle.

PMID- 18075127
TI  - Cages and chondrocytes: techniques to replace and regenerate the troublesome
      intervertebral disc.
AB  - Techniques for spinal surgery are developing apace, and there are divergent views
      on the merits of facilitating spinal fusion or attempting to replace or
      regenerate the degenerative intervertebral disc. The different strategies and
      preferred materials are described.

PMID- 18075128
TI  - Nanocrystalline material with gigacycle fatigue life.
AB  - A processing technology has been developed that can be applied to many different
      fine wire medical alloys to improve their fatigue properties. This technology has
      been used to process a low inclusion alloy, 35 cobalt-35 nitinol-20 chromium-10
      Molybdenum (ASTM F562 chemistry), hereinafter referred to as System A. After
      processing, this ultra fine microstructure exhibited relatively high yield
      strength, good axial ductility and a fatigue limit of 1 GPa at a fatigue lifetime
      that exceeded 100 million cycles, as reported here.

PMID- 18075129
TI  - Force testing medical tubing.
AB  - Force testing in the design and production of medical tubing is an essential
      ingredient in the delivery of functional and consistently high quality devices.
      This article describes a range of typical tests, how they are performed and the
      benefits they offer.

PMID- 18075130
TI  - Outsourcing to win.
AB  - The decision to outsource the manufacture of an entire device can be difficult,
      yet the advantages of this business strategy are huge. The important elements of
      the process are examined here so that companies can adopt this approach with
      confidence.

PMID- 18075131
TI  - Catheter hole making.
AB  - The science and technology of making good quality holes in tubing is an important
      issue for the success of the application. The process options and their benefits
      and limitations are examined.

PMID- 18075132
TI  - Incorporating human factors in product design and development.
AB  - A malfunctioning device causes problems, as does misuse by users. To reduce the
      risk of developing malfunctioning or misused products, companies are
      incorporating Human Factors Engineering (HFE) methods into the product design and
      development process. By integrating research, HFE and user interface design,
      companies can identify usage errors and differentiate their products from their
      competitors. This article describes several ways in which HFE can be used
      throughout the product development process, and provides some examples of
      products designed using HFE methods.

PMID- 18075133
TI  - Implementing new European vigilance procedures.
AB  - The new European vigilance guidelines come into force on 1 January 2008. In
      addition, the Directive amending the medical devices Directives, which includes
      some aspects of the vigilance system, was recently published. This article
      discusses the amendments concerning vigilance requirements, the new European
      vigilance guidelines and steps that manufacturers should take now to prepare for
      these.

PMID- 18075134
TI  - Contract manufacturers add contract design to their services.
AB  - Increasingly, contract manufacturers are offering design services to the
      industry. The advantages of this to medical device companies are outlined.

PMID- 18075135
TI  - How to achieve high-mix, low-volume manufacturing success.
AB  - Manufacturing an array of complex products in relatively small quantities is
      challenging. Outsourcing can be the answer. Here are some important questions to
      ask when selecting an electronics manufacturing services partner.

PMID- 18075136
TI  - Safety testing of medical devices: IEC 62353 explained.
AB  - The new IEC standard for the in-service and post repair testing of electromedical
      devices introduces new requirements. These and their implications are outlined.

PMID- 18075137
TI  - How to effectively partner with an automation company.
AB  - Essential factors to identifying the right automation company and the benefits
      that can be gained from partnering in the product concept phase.

PMID- 18075138
TI  - The German MedTech industry in 2007.
AB  - As innovation activity remains high on the industry's agenda, it is calling fora
      renewed focus on the economics of health care.

PMID- 18075139
TI  - [The physiology of wound healing].
AB  - Wound healing is a complex biological phenomenon. A variety of cellular and
      biochemical events take place designed to achieve tissue integrity following
      injury. Even though hypoxia caused by the damaged microvasculature is an
      important initial stimulus of the healing cascade, adequate tissue perfusion and
      oxygenation is an absolute pre-requisite for a successful repair since essential
      wound healing mechanisms such as collagen deposition and bactericidal defence are
      oxygen dependent reactions. Based upon these findings, there are several ways to
      overcome the obstacle of tissue hypoxia in clinical practice. Supplemental oxygen
      is capable of increasing tissue oxygen tension. Following surgery, pain, cold and
      to little fluids are the main issues of vasoconstriction, impaired tissue
      perfusion and oxygenation as well. However, all these parameters must be
      corrected at the same time because any one is sufficient to cause maximal
      vasoconstriction. A well hydrated, pain free and warm patient should be the main
      goal of peri- and postoperative surgical care.

PMID- 18075140
TI  - [Principles of wound treatment].
AB  - New techniques and devices have revolutionized the treatment of wounds during the
      last years. For the treatment of wounds we have nowadays a great variety of new
      gadgets, tools and methods. Complex wounds require specific skills, given the
      fact that a great number of different promising methods are on the market to
      enable an optimal wound management. Well educated "wound experts" are required to
      overcome the problems of very complicated and chronic wound problems. The
      importance of an interdisciplinary team increases while facing the problems of
      special wound disorders such as a diabetic food, food ulcers or the problems of
      open abdomen in case of severe peritonitis. In this overview the main principles
      of modern wound treatment are outlined. The aim of this article is to present a
      good summary of wound judgement and treatment for the practioner. Increasingly
      important is it to point out the situation of complexe wounds which should be
      judgded and treated with the help of a "wound expert".

PMID- 18075141
TI  - [The difficult wound].
AB  - Difficult wounds of different origin are a challenge for medical and custodial
      knowledge and capability. They are often characterised by a complex and
      protracted course of disease and cause considerable costs. Critical wounds
      particularly include chronic wounds such as venous stasis ulcers, diabetic foot
      ulcers or pressure ulcers and often lead to physical and psychosocial strain.
      Large-scale and deep wounds, wounds in traumatised tissue, wound complications
      and infections as well as wounds in patients with severe accompanying diseases or
      in patients of old age are often marked by a severe and unpredictable course and
      are therefore a threat for patients. Knowledge of characteristic symptoms and
      particularities of the course of disease are essential for early diagnosis and
      succsessful treatment. Despite many recent advances in wound care the management
      is often compounded by a lack of clearly defined, comprehensive wound care
      standards.

PMID- 18075142
TI  - [Vacuum therapy--basics, indication, contraindication and cost listing].
AB  - Vacuum therapy is an efficient alternative to conservative wound care and creates
      new possibilities for the treatment of a variety of chronic and acute wounds.
      Already more than two thousand years ago vacuum treatment was applied in
      traditional Chinese medicine and also today vacuum therapy is used more and more
      frequently in daily clinical practice. The positive effects of the therapy are
      based on the stimulation of blood flow, formation of granulation tissue,
      angiogenesis, as well as cell proliferation, accelerated secondary wound closure
      and the removal of bacteria from the wound. As can be demonstrated based on a
      clinical picture of the open abdomen, vacuum therapy based on KCI's (Kinetic
      Concepts Inc) VA.C. system (Vacuum Assisted Closure) provides a possibility for
      not only accelerating the healing process, but also significantly lowering
      mortality. Since vacuum therapy in the form of the V.A.C. system represents a
      relatively expensive intervention, a comparison with conventional healing methods
      is demonstrated. Clinical studies with high evidence level show that both
      economic and clinical advantages of the vacuum therapy speak for its application.
      Savings with respect to the faster healing rates, the reduced dressing changes,
      as well as hospital stay and the care requirements, and the reduction of
      subsequent illnesses, compensate for the higher initial costs. Although many
      reports exist on treatment successes with the application of V.A.C. therapy,
      there are several cases for which vacuum therapy is contraindicated. In order to
      make sure that V.A.C. therapy is effective, a range of precautions and
      contraindications are described. The European Wound management Association (EWMA)
      just wrote a position paper on V.A.C. therapy. This is available at www.ewma.org.

PMID- 18075143
TI  - [Burns--from trifle case to mass casualty].
AB  - Burn injuries are very frequent, most being trifle cases. Nevertheless every year
      about 200 patients need to be treated in one of the two specialised Swiss burns
      centres. Admission criteria are burns > 15% body surface or burns to critical
      areas (face neck, hands, genitalia, joints) and electrical injuries. The paper
      reviews the physiophathology of the burn wound which differs depending on the
      thermal or electrical aetiology. The airway may be threatened due to true
      inhalation, but also to burns to the face or neck. In major burns >20% body
      surface in adults, or > 10% in children, fluid resuscitation will be required;
      oral hydration is generally sufficient by smaller burns. Surgical treatment of
      2nd and 3rd degree burns starts within the first 24 days after injury. While
      complex treatment is generally available in peace time, a major accident such as
      a disco-fire that can generate hundreds casualties in a few minutes, can threaten
      our system and force the adoption of triage rules, and simplified treatments.
      Attitudes to adopt in such conditions are discussed.

PMID- 18075144
TI  - [Intestinal stomas--indications, stoma types, surgical technique].
AB  - The formation of an intestinal stoma is one of the most frequent operations in
      visceral surgery. Despite new operative techniques and a more restrictive use of
      the stoma, the stoma formation remains an often necessary surgical procedure,
      which results to a dramatic change in the patients' life. The stoma formation and
      its later closure are associated with a high morbidity. Many complications, such
      as stoma necrosis, stoma retraction or stoma prolapse, are related to surgical
      mistakes made during stoma formation. These complications are therefore largely
      avoidable. The stoma formation needs careful planning together with a
      professional stoma nursing team. Moreover, it is mandatory that the stoma
      formation is made with great care and that it meticulously follows the well
      established surgical principles. A perfectly placed, technically correctly
      fashioned and easy to care for stoma is essential for a good patients'quality of
      life.

PMID- 18075145
TI  - [Metabolic consequences in patients with intestinal stoma].
AB  - In addition to psychological stress, stomas may lead to metabolic consequences.
      Colostomies normally cause only minor physiological problems; however, patients
      with ileostomies are at risk for severe metabolic disturbances. The small
      intestine essentially manages the balance of water and electrolytes and the
      absorption of nutrition. In special circumstances such as or short-bowel
      syndrome, dangerous consequences like kidney disorders may arise. Basic
      therapeutic strategies such as enteral or parenteral substitution are discussed.

PMID- 18075146
TI  - [The complicated stoma--late complications, conservative and surgical
      management].
AB  - Creation of a stoma is related with up to 50% complications. Two main causes are
      recognised: stomacare and positioning of the stoma. During the first few weeks
      the diameter of the stoma may shrink by 1/3. In this phase without the
      professional aid by a stomatherapist the risk of skin problems increases with
      time. Late complications as prolapse, parastomal hernia and stenosis are often
      the result of a too lateral positioning of the stoma or of early complications as
      necrosis, dehiscence, retraction and parastomal abscess. If conservative
      treatment does not solve the problem surgical procedures are warranted. Beside
      local corrections replacement of the stoma may be needed. However this is a major
      operation. Therefore, replacement should be the last option to resolve stoma
      complications.

PMID- 18075147
TI  - [The patient with a stoma].
AB  - After formation of a stoma patients quality of life can be compromised. This
      includes body image, capacity to work, leisure time and sexual activity. After
      leaving the hospital it is essential, that stoma patients are supported by
      professionals on the long run. This can be achieved by a network of stoma-care
      nurses, social workers and psychology professionals.

PMID- 18075148
TI  - [Patient education, perioperative management, patient support groups].
AB  - In our division, highly qualified enterostomal therapists treat approximately 300
      patients each year Patient care consists of extensive preoperative information,
      localization of the ideal stoma position and providing patient-education in stoma
      handling. A regular ambulatory consultation allows early recognition of typical
      stoma related complications and their effective treatment in a timely manner.
      Another important issue of our consulting service includes patients concerns,
      such as social integration and physical independence. The creation of a
      specialized center provides an efficient and continuous care of enterostomy
      patients and their relatives. Thus, initial fears and emotional crisis can be
      addressed and minimalized. It is our goal to provide individual and comprehensive
      service in order to accommodate our patients needs.

PMID- 18075149
TI  - [Historical context of parasitological studies in tropical area, malaria as an
      example].
AB  - Review paper deals with the historical analysis of intellectual activity of some
      famous parasitologists working in tropics on malaria in the XIX/XX century: A.
      Laveran (1845-1922), R. Ross (1857-1932), P. Manson (1844-1922), B. Grassi (1854
      1925), and other Nobelprize researchers: P. H. Muller (1899-1965) and J. W. von
      Jauregg (1857-1940). Those chief investigations are interpreted from the point of
      view of the so-called anthropology of knowledge based on L. Fleck's (1896-1961)
      philosophy and sociology of science. Parasitological investigations, especially
      in the field of malaria, were undertaken in the developed economically countries
      in answer to the social demands. It was connected with development of colonies
      and the needs of stabilization of epidemiological situation in tropics. To mid of
      the eigthies of 19th century the lack of positive effects resulted from the
      theoretical barriers and conservative thinking style of the European academic
      society. It caused that great parasitological discoveries of the etiological
      agents of parasitic diseases (like plasmodia, life cycle in malaria) took place
      behind university circles. They were done by the physicians - general
      practitioners--in the colony areas. Doctors A. Laveran, P. Manson and R. Ross
      were not restricted by traditional standards and the obliging normative concepts
      in the academic naturalism. Those medical men worked out a new impulse for
      parasitology and supported an idea based on the rule that each disease should be
      assigned with the materialistic biological factor (pathogen). In the years 1800
      1900 the old and a new concepts were competed in the natural sciences and
      medicine. Near year 1900 a new way in the context of modern interpretations was
      brought into general use. It was proved experimentally that etiological theory of
      parasitic disease was more practically usuful. It resulted in the formation of
      the effective prophylactic theory as well as the development of research in the
      field of chemotherapy. For that reason this thinking style was accepted by the
      state authorities and armies interested in possessing colonies. The governments
      organized and financed scientific institutes of tropical medicine and the
      hygienic parasitological journals. Also the researchers (A. Laveran, R. Ross, P.
      Manson) were rewarded for their epoch-making investigations in tropical disease
      problems. At the same time the progress in parasitology was prompted and the old
      theories in old thinking style were eliminated as false because of their
      practical uselessness. Their followers lost status of authorities. This analysis
      proved that external factors of science, i.e. social needs in historic periods
      play real role in the promoting of changes of scientific standards in the
      perception of new standards. Social needs form the broad social-cultural context
      of scientific activity and they influence seriously the way of thinking and
      investigations practice.

PMID- 18075150
TI  - [Guidelines for diagnosis and treatment of liver alveococcosis caused by
      Echinococcus multilocularis].
AB  - Recent epidemiological reports have shown an increasing incidence of Echinococcus
      multilocularis infection among red foxes and inhabitants from Pomorskie,
      Warminsko-Mazurskie and Podkarpackie Districts of Poland. The study describes the
      actual recommendations for a proper diagnosis and optimal treatment in patients
      infected with E. multilocularis in order to standardize diagnostic and
      therapeutic procedures for this severe parasitic disease by reference centres.
      Liver lesions caused by the parasite were visualised by ultrasonography and
      computerized tomography scan. The clinical diagnosis based on typical imaging
      findings was completed by Em2plus ELISA and Em16 and Eml18 Western blot
      immunodiagnostic tests using specific antigens, and confirmed by positive
      histopathological and/or molecular examinations. Since 1992, forty-five cases of
      alveolar echinococcosis were registered in Poland. Professions related to
      forestry or picking-up mushrooms and blueberries were potential risk factors for
      an occurrence of the infection, especially in the northern region of the country.
      In the imaging techniques, the liver lesions were characterized by heterogenous,
      irregular masses with necrotic cavities, and clausters of calcifications located
      in the peripheral parts. The final diagnosis of alveococcosis was based on PAS
      positive staining of lesions in histopathology and/or the detection of the
      parasite's DNA in liver sections by PCR. The patients were treated by radical
      surgery with concomitant long-term intensive chemotherapy with albendazole.
      CONCLUSIONS: Collaboration with physicians of various medical specialities is
      crucial for an early and more effective detection of alveococcosis in Poland. E.
      multilocularis infection should always be considered in the differential
      diagnosis of space-occupying lesions in the liver characterized by irregular
      heterogenous masses, suggesting slow tumor growth.

PMID- 18075151
TI  - [The vaccines against toxoplasmosis--current status of the studies].
AB  - The article presents current studies on the development of effective vaccines
      against toxoplasmosis new approaches and strategies to construct prophylactic and
      therapeutic vaccines using recombinant microorganisms expressing protective T.
      gondii antigens, parasite DNA or RNA and recombinant antigens.

PMID- 18075152
TI  - [The investigations of the role of toll-like receptors (TLR) in host response to
      parasitic infection on the current background regarding TLR in mammals and the
      model nematode Caenorhabditis elegans].
AB  - Toll-like receptors (TLRs) are amongst the most highly conserved in the evolution
      of receptor family, being found in both immune and other cells. TLRs were
      observed in vascular endothelial cells, epithelial cells, microglia cells,
      adipocytes, and intestinal and renal cells. TLRs plays a key role in the innate
      immune response to a variety of pathogens. At present, very little is known about
      the role of TLRs in host defense against parasitic pathogen infections. The first
      study shows that TLRs contribute to both innate and adaptive immune responses
      following infection with protozoan parasite Leishmania major. The TLRs
      recognizing PAMPs associated with the parasite L. major are essential for the
      activation of the innate and adaptive immune responses to infection. A study
      concerning recognition of the role of TLRs in the host-parasite relationship
      would be an interesting challenge for future study.

PMID- 18075153
TI  - [Trends of faunistic-ecological researches in the Department of Parasitology in
      Wroclaw University].
AB  - Paper deals with the results of systematic-ecological investigations of host
      parasite relationships in the context of 45 year history of the Parasitological
      Department at the University of Wroclaw. Achievements are concentrated on the
      presentations of new taxonomic units and rearrangement of classification of
      parasitic protozoans and tapeworms (J. Janiszewska), nematodes (A. Okulewicz),
      lice (J. Zlotorzycka, E. Lonc, M. Modrzejewska). Faunistic and biometrical data
      of parasitic commities of fishes, birds and mammals, mainly rodents as well as
      the vector role of ticks and mosquitoes at Wroclaw area are also discussed.
      Localities of those parasites and their hosts, collected mainly from the Lower
      Silesia region are rearranged according to new system of physicogeographic
      differentiation of Poland and its regional position at biogeographical map of
      world.

PMID- 18075154
TI  - [A comparison of soil contamination with Toxocara canis and Toxocara cati eggs in
      rural and urban areas of Wielkopolska district in 2000-2005].
AB  - The aim of the studies was to compare the degree of soil contamination with
      Toxocara canis and T. cati eggs in rural and urban areas depending on time of
      sampling and type of places examined. Material and methods. Over 2000-2005 a
      total of 538 soil samples from 3 villages and 368 from Poznan city (Poland) areas
      were examined for Toxocara spp. eggs. In spring 418 samples in rural areas and
      184 samples in urban areas were collected and in autumn 120 and 184 respectively.
      The samples were examined using flotation technique in saturated sodium nitrate.
      The discrimination of T. canis and T. cati eggs was based on the size of eggs and
      transparency of shell layers. Results. The contamination of soil with Toxocara
      eggs was higher in the urban areas (19.8% positive samples) than in the rural
      ones (15.6% positive samples) and city or village-backyards were most heavily
      contaminated. Both, in the villages and in the city, the degree of soil
      contamination with eggs in spring and autumn was similar (17.6 and 14.8% positive
      samples respectively). T. cati eggs were much more prevalent in urban areas (97%
      of all eggs recovered) while T. canis in rural areas (84% of all recovered eggs).
      The share of T. canis and T. cati eggs in soil contamination did not depend on
      the time of sampling.

PMID- 18075155
TI  - [Contamination of playgrounds in Gdansk city with parasite eggs].
AB  - INTRODUCTION: Nematodes of Toxocara genus are common parasites of dogs and cats.
      These animals are the main source of dangerous zoonoses. The main source of
      toxocarosis among children are sandpits which are contaminated with dog and cat
      faeces. We examined the contamination of playgrounds with parasite eggs in
      Gdatisk city, and frequency of infections of dogs and cats in the area under
      study. MATERIAL AND METHODS: Samples of sand were taken from a surface of
      sandpits (to depth about 3 cm). All samples were collected in amount of 100 g.
      Samples of faeces were taken from various places of the playgrounds. Two methods
      were applied: flotation and decantation by Fulleborn-Willis in modification by
      W6jcik. RESULTS: Out of 162 sand samples examined 21 (13%) were positive. Out of
      54 faeces samples examined 23 (42.6%) were positive. We observed some differences
      in the degree of parasite species occurrence. The most dominated were Toxocara
      spp. (6.2% in sand samples and 11% in faeces samples) and Toxascaris leonina (11%
      in faeces). Eggs of Uncinaria stenocephala and Ancylostoma canimum, as well as
      proglotides of Dipylidium caninum were found sporadically.

PMID- 18075156
TI  - [Significance of red deer (Cervus elaphus) in the ecology of Borrelia burgdorferi
      sensu lato].
AB  - BACKGROUND: Red deer (Cervus elaphus) is one of the most important host of the
      adult tick (Ixodes ricinus) which is the basic vector of the Lyme disease
      causative agent--Borrelia burgdorferi sensu lato in Europe. The aim of the
      present study was to establish the role of red deer in the transmission of B.
      burgdorferi s.1. Material and methods. Tissues from 74 red deers were evaluated
      and the presence of B. burgdorferi s.1 DNA was identified using nested PCR
      technique based on fla gene. The identification of species belonging to B.
      burgdorferi s.1 complex was performed after restriction digestion of nested PCR
      product with Ddel enzyme and sequencing of nested PCR product. The study included
      also 55 isolates of I. ricinus females removed from red deer and 466 ticks (73
      adult and 393 nymphs) collected from the vegetation in the area where the red
      deer lives. RESULTS: There were no DNA of B. burgdorferi s.1 complex in the red
      deer tissues and in ticks removed from deer, however in one tick removed from
      deer the DNA of other Borrelia species--B. miyamotoi was identified. In ticks
      collected from vegetation 3 species belonging to B. burgdorferi s.1. complex were
      identified: B. garinii (3.2% ticks studied), B. afzelii (6.9%) and B. valaisiana
      (3.6%), however DNA of B. miyamotoi was absent. These results confirm inability
      of survival of B. burgdorferi s.1. species in tick I. ricinus feeding on red deer
      blood. However there is a possibility of survival of B. miyamotoi in presence of
      deer blood at least in ticks feeding on red deer. The main role of red deer in
      keeping the constant infection level of B. burgdorferi s.1. in the whole
      population of I. ricinus ticks does not concern B. miyamotoi.

PMID- 18075157
TI  - [Oesophagostomum quadrispinulatum (Marcone, 1901) Alicata, 1935--a new for Poland
      parasite of swine].
AB  - MATERIAL AND METHODS: Large intestines of five slaughtered sows, aging 10 months
      to 3 years and originating from different herds of southern Poland, were examined
      parasitologically according to an agar-gel method. The intestines were uncoiled
      and divided into three sections: section 1--caecum and the first 0-20% part of
      colon, section 2-20--60% of large intestine and section 3--60-100% length of gut.
      Adult worms of Oesophagostomum were differentiated on the basis of species and
      sex, using the shape of buccal capsule and oesophagus, the length of male
      spicules, and the distance from vulva to anus as well as from anus to the tip of
      tail of females. RESULTS: In the case of two sows, in 30% of the contents from
      the section 1 of large intestines a total of 10 specimens of Oesophagostomum
      quadrispinulatum (Marcone, 1901) Alicata, 1935 were found. This is a new nematode
      species in the parasitic fauna of Poland and the present record enlarges its
      geographical range. The infection with O. quadrispinulatum seems to be more
      dangerous from that of O. dentatum--the most common porcine nodular worm.

PMID- 18075158
TI  - Detection of the high risk pyrethroid resistant Varroa destructor mites in
      apiaries of the Warmia-Mazury province in Poland.
AB  - BACKGROUND: The aim of our current study was to investigate the possible
      occurence of pyrethroid (taufluvalinate) resistant Varroa mites infestations in
      24 randomly chosen apiaries of Warmia-Mazury province of northeast Poland.
      METHODS: The methodology used for the analysis of resistant Varroa strains
      strictly followed the protocol described by Milani. RESULTS: We identified 3
      apiaries that were infested with high risk pyrethroid resistance mites and a
      further 9 apiaries that were free from this resitance. The brood samples
      collected from the remaining apiaries did not contain sufficient numbers of
      parasites to enable us to properly perform the assay. CONCLUSIONS: Our finding
      that 25% of the tested brood samples showed a high risk of fully pyrethroid
      resistant Varroa mite contamination indicates that resistant Varroa may become
      wide spread in apiaries in Poland. Interestingly these high risk resistant mites
      were found in honeybee colonies with low levels of Varroa infestation, with an
      average rate of 2.16%. We also discuss the role of amitraz (amidine) in the
      phenomenon of Varroa resistance to pyrethroids.

PMID- 18075159
TI  - [The impact of nematode invasions on the pattern of Cryptosporidium parvum
      infection in wild rodents].
AB  - Fragmentation of the environment by natural barriers (lakes, mountain ranges) and
      human activities (towns, major roads, agriculture) can lead to isolated
      subpopulations of hosts. The study was carried out in Mazury Lake District in
      North-East of Poland, the region rich in forests, lakes, rivers and canals, which
      are able to create passable such barriers. Population of bank voles (Myodes
      glareolus) and yellow-necked mice (Apodemus flavicollis)--dominant woodland
      rodents--showed local differences in helminth communities in fragmented forest
      habitat. The sites were chosen on the basis of the similarity of their habitat
      structure and type, and isolation from one another. The impact of nematode
      (Heligmosomoididae) infections on co-occurrence and dynamic of Cryptosporidium
      parvum infection was studied in both rodent species Myodes glareolus (n=781) and
      Apodemusflavicollis (n=302) from three different habitats. Presented results
      clearly revealed that natural nematode invasion could facilitate the presence of
      chronic infections of Cryptosporidium parvum in wild rodent populations. Also,
      the intrinsic (host sex and year) as well as extrinsic (season and year of study)
      factors have obvious effect on dynamics of infections with both groups of
      parasites. However, there are also some evidences that steroids hormones
      associated with stress and reproduction may mediate trade-offs between physiology
      and immune function and can affect co-occurrence of both groups of parasites.

PMID- 18075160
TI  - A historical perspective of template-based protein structure prediction.
AB  - This chapter presents a broad and a historical overview of the problem of protein
      structure prediction. Different structure prediction methods, including homology
      modeling, fold recognition (FR)/protein threading, ab initio/de novo approaches,
      and hybrid techniques involving multiple types of approaches, are introduced in a
      historical context. The progress of the field as a whole, especially in the
      threading/FR area, as reflected by the CASP/CAFASP contests, is reviewed. At the
      end of the chapter, we discuss the challenging issues ahead in the field of
      protein structure prediction.

PMID- 18075161
TI  - The assessment of methods for protein structure prediction.
AB  - Methods for protein structure prediction are flourishing and becoming widely
      available to both experimentalists and computational biologists. But, how good
      are they? What is their range of applicability and how can we know which method
      is better suited for the task at hand? These are the questions that this chapter
      tries to address, by describing automatic evaluation methods as well as the world
      wide Critical Assessment of Techniques for Protein Structure Prediction (CASP)
      initiative and focusing on the specific problems of assessing the quality of a
      protein 3D model.

PMID- 18075162
TI  - Aligning sequences to structures.
AB  - Most newly sequenced proteins are likely to adopt a similar structure to one
      which has already been experimentally determined. For this reason, the most
      successful approaches to protein structure prediction have been template-based
      methods. Such prediction methods attempt to identify and model the folds of
      unknown structures by aligning the target sequences to a set of representative
      template structures within a fold library. In this chapter, I discuss the
      development of template-based approaches to fold prediction, from the traditional
      techniques to the recent state-of-the-art methods. I also discuss the recent
      development of structural annotation databases, which contain models built by
      aligning the sequences from entire proteomes against known structures. Finally, I
      run through a practical step-by-step guide for aligning target sequences to known
      structures and contemplate the future direction of template-based structure
      prediction.

PMID- 18075163
TI  - Protein structure prediction using threading.
AB  - This chapter discusses the protocol for computational protein structure
      prediction by protein threading. First, we present a general procedure and
      summarize some typical ideas for each step of protein threading. Then, we
      describe the design and implementation of RAPTOR, a protein structure prediction
      program based on threading. The major focuses are three key components of RAPTOR:
      a linear programming approach to protein threading, two machine learning
      approaches (SVM and Gradient Boosting) to fold recognition, and evaluation of the
      statistical significance of the prediction results. The first part of this
      chapter is a brief review of protein threading, and the second part contains
      original research results. Some key ideas and results have been previously
      published.

PMID- 18075164
TI  - Algorithms for multiple protein structure alignment and structure-derived
      multiple sequence alignment.
AB  - Primary amino acid content and the geometry of the folded protein 3D structure
      are major parameters of protein function. During the course of evolution the
      protein 3D structure is more preserved than its primary sequence. Thus, analysis
      of protein structures is expected to lead to a deep insight into protein
      function. Recognition of a structural core common to a set of protein structures
      serves as a basic tool for the studies of protein evolution and classification,
      analysis of similar structural motifs and functional binding sites, and for
      homology modeling and threading. In this chapter, we discuss several biologically
      related computational aspects of the multiple structure alignment and propose a
      method that provides solutions to these problems. Finally, we address the problem
      of structure-based multiple sequence alignment and propose an optimization method
      that unifies primary sequence and 3D structure information.

PMID- 18075165
TI  - Indexing protein structures using suffix trees.
AB  - Approaches for indexing proteins and fast and scalable searching for structures
      similar to a query structure have important applications such as protein
      structure and function prediction, protein classification and drug discovery. In
      this chapter, we describe a new method for extracting the local feature vectors
      of protein structures. Each residue is represented by a triangle, and the
      correlation between a set of residues is described by the distances between
      Calpha atoms and the angles between the normals of planes in which the triangles
      lie. The normalized local feature vectors are indexed using a suffix tree. For
      all query segments, suffix trees can be used effectively to retrieve the maximal
      matches, which are then chained to obtain alignments with database proteins.
      Similar proteins are selected by their alignment score against the query. Our
      results show classification accuracy up to 97.8 and 99.4% at the superfamily and
      class level according to the SCOP classification and show that on average 7.49
      out of 10 proteins from the same superfamily are obtained among the top 10
      matches. These results outperform the best previous methods.

PMID- 18075166
TI  - Hidden Markov Models for prediction of protein features.
AB  - Hidden Markov Models (HMMs) are an extremely versatile statistical representation
      that can be used to model any set of one-dimensional discrete symbol data. HMMs
      can model protein sequences in many ways, depending on what features of the
      protein are represented by the Markov states. For protein structure prediction,
      states have been chosen to represent either homologous sequence positions, local
      or secondary structure types, or transmembrane locality. The resulting models can
      be used to predict common ancestry, secondary or local structure, or membrane
      topology by applying one of the two standard algorithms for comparing a sequence
      to a model. In this chapter, we review those algorithms and discuss how HMMs have
      been constructed and refined for the purpose of protein structure prediction.

PMID- 18075167
TI  - The pros and cons of predicting protein contact maps.
AB  - Is there any reason why we should predict contact maps (CMs)? The question is one
      of the several 'NP-hard' questions that arise when striving for feasible
      solutions of the protein folding problem. At some point, theoreticians started
      thinking that a possible alternative to an unsolvable problem was to predict a
      simplified version of the protein structure: a CM. In this chapter, we will
      clarify that whenever problems are difficult they remain at least as difficult in
      the process of finding approximate solutions or heuristic approaches. However,
      humans rarely give up, as it is stimulating to find solutions in the face of
      difficulties. CMs of proteins are an interesting and useful representation of
      protein structures. These two-dimensional representations capture all the
      important features of a protein fold. We will review the general characteristics
      of CMs and the methods developed to study and predict them, and we will highlight
      some new ideas on how to improve CM predictions.

PMID- 18075168
TI  - Roadmap methods for protein folding.
AB  - Protein folding refers to the process whereby a protein assumes its intricate
      three-dimensional shape. This chapter reviews a class of methods for studying the
      folding process called roadmap methods. The goal of these methods is not to
      predict the folded structure of a protein, but rather to analyze the folding
      kinetics. It is assumed that the folded state is known. Roadmap methods maintain
      a graph representation of sampled conformations. By analyzing this graph one can
      predict structure formation order, the probability of folding, and get a coarse
      view of the energy landscape.

PMID- 18075169
TI  - Scoring functions for de novo protein structure prediction revisited.
AB  - De novo protein structure prediction methods attempt to predict tertiary
      structures from sequences based on general principles that govern protein folding
      energetics and/or statistical tendencies of conformational features that native
      structures acquire, without the use of explicit templates. A general paradigm for
      de novo prediction involves sampling the conformational space, guided by scoring
      functions and other sequence-dependent biases, such that a large set of candidate
      ("decoy") structures are generated, and then selecting native-like conformations
      from those decoys using scoring functions as well as conformer clustering. High
      resolution refinement is sometimes used as a final step to fine-tune native-like
      structures. There are two major classes of scoring functions. Physics-based
      functions are based on mathematical models describing aspects of the known
      physics of molecular interaction. Knowledge-based functions are formed with
      statistical models capturing aspects of the properties of native protein
      conformations. We discuss the implementation and use of some of the scoring
      functions from these two classes for de novo structure prediction in this
      chapter.

PMID- 18075170
TI  - Protein-protein docking: overview and performance analysis.
AB  - Protein-protein docking is the computational prediction of protein complex
      structure given the individually solved component protein structures. It is an
      important means for understanding the physicochemical forces that underlie
      macromolecular interactions and a valuable tool for modeling protein complex
      structures. Here, we report an overview of protein-protein docking with specific
      emphasis on our Fast Fourier Transform-based rigid-body docking program ZDOCK,
      which is consistently rated as one of the most accurate docking programs in the
      Critical Assessment of Predicted Interactions (CAPRI), a series of community-wide
      blind tests. We also investigate ZDOCK's performance on a non-redundant protein
      complex benchmark. Finally, we perform regression analysis to better understand
      the strengths and weaknesses of ZDOCK and to suggest areas of future development
      for protein-docking algorithms in general.

PMID- 18075171
TI  - Molecular dynamics simulations of protein folding.
AB  - I illustrate the use of the replica exchange molecular dynamics (REMD) algorithm
      to study the folding of a small (57 amino acids) protein that folds into a three
      helix bundle, protein A. The REMD is a trivially parallel method that uses
      multiple copies of the system of interest to study the canonical ensemble
      equilibrium properties. Each replica represents a different thermodynamic state,
      usually at different temperatures. This method enhances the configurational
      sampling of proteins and allows us to study folding in simulations that are much
      shorter than the folding timescale for the system at ambient temperature. I show
      that using REMD and the Amber force field, I can obtain stable configurations of
      protein A whose backbone root mean square distance (RMSD) is within 0.17 nm of
      the nuclear magnetic resonance (NMR)-determined structure without biasing the
      system toward the folded structure. The simulations are done in explicit solvent
      and starting from nearly extended configurations. This calculation shows that
      currently available force fields and enhanced sampling methods perform reasonably
      well in describing the folded structure of small proteins.

PMID- 18075173
TI  - Hydraulic and pollutant removal performance of stormwater filters under variable
      wetting and drying regimes.
AB  - Biofiltration systems are an effective stormwater treatment technology. However,
      their robustness is yet to be tested, particularly their performance following
      extended dry periods. The hydraulic and treatment performance of five different
      non-vegetated, soil-based filters under varying periods of inundation and drying
      was assessed. The infiltration capacity of the filters decreased during wet
      periods and increased following dry periods, most probably due to swelling and
      shrinkage of the filter media. Treatment of sediment, heavy metals and phosphorus
      was not influenced by the wetting and drying regime. However, outflow
      concentrations of nitrogen were significantly higher upon re-wetting following
      extended dry periods compared with wet periods. This result has implications for
      current design practices, as these nitrogen pulses could negatively impact the
      ecological health of downstream receiving waters.

PMID- 18075172
TI  - Statistical evaluation and optimisation of stormwater quality monitoring
      programmes.
AB  - This paper reports on a statistical review of a water quality monitoring
      programme aimed at estimating long-term pollutant loads discharged from waterways
      in and around Melbourne, Australia. Performance of the current programme was
      evaluated with respect to the required level of uncertainty to meet management
      objectives. Use of continuously measured turbidity was found to be an effective
      surrogate measure for estimating TSS, with errors in long-term load estimates of
      less than 5%. Where routine grab sampling was used instead, errors increased with
      sampling interval; a 3-day interval was required to maintain errors within 10% of
      the continuously measured load. For storm event sampling, auto-samplers were
      found not to be required, if only long-term load estimates are required. The
      importance of eliminating systematic errors, by ensuring frequent calibration and
      data verification, was demonstrated.

PMID- 18075174
TI  - Characteristics of urban run-off derived sediments captured by proprietary flow
      through stormwater interceptors.
AB  - Sediment entrained in urban run-off is acknowledged as being an important carrier
      of pollutants. The paper reports on the physical and chemical characteristics of
      sediments captured by six installations of a proprietary interceptor device. The
      sites, located in the United Kingdom and the Republic of Ireland, were selected
      to represent a range of urban contexts. Particle D(50) values were found to range
      from 7 to 112 mum, corresponding with ranges reported for stormwater ponds. Heavy
      metal and hydrocarbon concentrations were also found to vary, with the highest
      corresponding to the most established and heavily trafficked sites. Further to
      confirming the ability of the interceptor to remove contaminated sediments,
      useful insights are provided into the interrelation between sediment
      characteristics and site conditions.

PMID- 18075175
TI  - Sewer storage tank performance under climate change.
AB  - This paper describes a study of the potential effects of climate change on the
      design and performance of sewer storage tanks. A long-term synthetic rainfall
      time-series has been derived based on the IPPC medium-high emission scenario for
      a case study in London. Results indicate a 35% increase in the number of storm
      events that cause filling of the tank and a 57% increase in the average volume of
      storage required. A method to estimate the required future storage volume for any
      given return period has been developed and described. Indications are that
      significantly larger storage volumes will be required to maintain the same level
      of flood protection.

PMID- 18075176
TI  - A metamodel for stormwater detention basins design.
AB  - The aim of storm basins is to protect urban areas against some predefined risk of
      exceeding a given value of downstream runoff, or a risk of overflow for a bounded
      storage capacity. This risk results from the combination of a natural hazard and
      hydraulic properties. The correct way to address this issue is to use a
      stochastic rainfall model, but it may require unavailable data and be cumbersome
      to use in the framework of an optimisation procedure. We give the end user a way
      to by-pass this step, by means of a metamodel. The problem is to calculate the
      parameters of the probability density function (pdf) of outputs as a function of
      the pdf of inputs and of the parameters of the dynamic deterministic system
      between inputs and outputs. We propose to apply a metamodel, which is a new way
      of designing approximate but generic derived distribution, based on conditional
      probabilities. For application to dimensioning of basins, the determination of
      the parameter(s) corresponding to an acceptable risk simply consists of solving
      an algebraic equation representing the metamodel. The methodology needs usual
      rainfall statistics and a specific parameter inferred from analysis of storms, or
      supposed to have a regional value.

PMID- 18075177
TI  - Estrogenic personal care products in a greywater reuse system.
AB  - The occurrence and fate of parabens in a greywater system was assessed. The
      potential for removal of residual paraben concentrations in effluent greywater
      with chlorine dioxide was also investigated. The influent to the greywater plant
      was characterised by considerable variation, with concentrations from below the
      detection limit to 40 microg/L and the five commonly used parabens in consumer
      products were frequently detected. After the biological treatment only two
      paraben were detected with concentration from 65-120 ng/L. Chlorine dioxide
      treatment of the biologically treated effluent with dosages down to 0.75 mg/L
      resulted in more than 97% reduction of all parabens. Formation of the by-product
      chloroform was insignificant from the chlorine dioxide treatment.

PMID- 18075179
TI  - Assessment of alkylphenols in wastewater treatment: do we comply with new
      directives?
AB  - The fate of various alkylphenolic compounds during wastewater treatment was
      studied at full scale in thirteen plants, selected in order to cover a wide range
      of treatment processes, sizes and countries. In-depth investigations consisted in
      the analysis of nonylphenols, short chained (n = 1, 2) but also long chained
      polyethoxylates in raw wastewaters, effluents, raw and treated sludges. The
      degradation of long chained polyethoxylates (APnEO) was shown, resulting in
      significant production of alkylphenols that concentrate in the sludges. Results
      show however that the pending Directive on spreading of sludge on land would be
      complied with in all cases. For the effluent, the EQS established within the WFD
      might not be satisfied in very critical situations where the dilution factor of
      the effluent in the river would be too small.

PMID- 18075178
TI  - Development of normal human colon cell cultures to identify priority unregulated
      disinfection by-products with a carcinogenic potential.
AB  - Research was initiated to develop an in vitro system to identify disinfection by
      products with a potential to transform normal human colonocytes into malignant
      cells. Tribromomethane and bromochloroacetic acid, rodent colon carcinogens,
      dibromonitromethane and tribromonitromethane, recently identified in drinking
      water, and azoxymethane, a classic colon carcinogen, were tested for the ability
      to transform NCM460 cells. The chronic toxicity was determined for the series of
      trihalomethanes, haloacetic acids and halonitromethanes as well as NCM460 cell
      enzymatic capabilities. The order of cytotoxicity was halonitromethanes >
      haloacetic acids > trihalomethanes. Cytotoxicity within a series increased with
      the degree of bromination and decreased with the molecular weight. The
      genotoxicity profile was similar to that for cytotoxicity. Enzymatic analysis
      demonstrated that NCM460 cells possess glutathione-S transerase-1-1 and CYP450
      activity similar to that measured in the large intestine. NCM460 cells were
      exposed to 10(-6) M of the test chemicals for three days. While NCM460 cells from
      all treatments had the ability to grow in soft agar to some extent, only cells
      exposed to azoxymethane or tribromomethane were able to grow in media lacking
      serum and growth factors. When sub cultured, NCM460 cells exposed to 10(-9) M
      azoxymethane for three weeks formed colonies with morphology distinct from
      untreated cells.

PMID- 18075180
TI  - Biocides used in building materials and their leaching behavior to sewer systems.
AB  - There is increasing concern about diffuse pollution of aquatic systems by
      biocides used in urban areas. We investigated sources and pathways of biocides
      significant for the pollution of storm water runoff. Main sources seem to be
      building envelopes, i.e. facades (paints, plasters) and roof sealing membranes.
      First results from a defined urban catchment drained by a separated sewer system
      without any agricultural activities reveal a substantial occurrence. Even after
      the first flush, concentrations of terbutryn, carbendazim, mecoprop as well as
      Irgarol 1051 and its metabolite exceeded the Swiss water quality standard of 0.1
      microg/L. In laboratory experiments, leaching of mecoprop used as a root
      protection agent in bitumen sheets for roof waterproofing was determined. The
      concentrations differed in 16 different sheets two orders of magnitude, depending
      on the product composition. Using optimized products, it is expected to be the
      most efficient and sustainable way to reduce the environmental impact. To
      understand transport dynamics and environmental risk, further storm water events
      will be analyzed. Based on the ongoing project URBIC, first measures will be
      proposed to limit the release to surface and ground water.

PMID- 18075181
TI  - Contributing to the sustainable use of stormwater: the role of pervious
      pavements.
AB  - The city of Melbourne, Australia is experiencing a water crisis with potable
      water storage reservoirs at an all time low. With increasing urbanisation there
      is an ever increasing need to research and explore sustainable water management
      initiatives. There is potential to minimise the negative impacts of stormwater
      runoff and augment dwindling supplies of potable water through adoption of
      pervious paving technology. The traditional approach to stormwater management has
      focused on constructing drainage networks to carry stormwater away from developed
      areas as quickly as possible to avoid the risk of flooding. The main aim of this
      research project was to establish relationships between rainfall intensity,
      infiltration rate and pervious pavement runoff and to examine the improvement to
      stormwater quality after infiltrating through pervious pavements. This paper
      describes the laboratory experiment set-up to determine the infiltration patterns
      and stormwater quality improvement for simulated storms precipitating on pervious
      pavements. Next, the scaling-up of the experimental rig to a field-based trial is
      explained. Preliminary results from this work are presented to demonstrate the
      potential benefits of pervious pavements in the Australian landscape.

PMID- 18075182
TI  - An investigation of wash-off controlling parameters at urban and commercial
      monitoring sites.
AB  - The relationship between the parameters of the wash-off function and the
      controlling hydrologic variables are investigated in this paper, assuming that
      the pollutant generation process basically depends on the watershed rainfall
      runoff response characteristics. Data collected during an intense monitoring
      program carried out by the Department of Environmental Engineering of the
      University of Genova (Italy) within a residential area, an auto dismantler
      facility, a tourism terminal and a urban waste truck depot are used to this aim.
      The observed runoff events are classified into different TSS mass delivery
      processes and the occurrence of the first flush phenomenon is also investigated.
      The correlation between the mathematical parameters describing the exponential
      process and the hydrological parameters of the corresponding rainfall-runoff
      event is analysed: runoff parameters and in particular the maximum flow discharge
      over the time of concentration of the drainage network are proposed as the
      controlling factor for the total mass of pollutant that is made available for
      wash-off during each runoff event.

PMID- 18075183
TI  - CSO treatment strategy based on constituent index relationships in a highly
      urbanised catchment.
AB  - In urbanising catchments the variability of particulate matter (solids) and
      oxygen demanding constituents of wet weather and dry weather characteristics
      result in variable treatment effectiveness from physical unit operations and
      biological unit processes. Higher organic concentrations during dry weather flow
      are more amenable to biological unit processes while the higher inorganic loads
      generated largely by urban wet weather constituents and much larger flows can be
      more effectively treated or conditioned by physical unit operations, including
      ideally preceded by hydrologic controls. This study examines the relationships
      between total chemical oxygen demand (COD)(t), dissolved chemical oxygen demand
      (COD)(d), particulate chemical oxygen demand (COD)(p) and solids, measured as
      total suspended solids (TSS). Results also provide an index for selection and
      optimisation of treatment operations for combined sewer overflow (CSO) loads.

PMID- 18075184
TI  - Temporal evolution and spatial distribution of heavy metals in a stormwater
      infiltration basin--estimation of the mass of trapped pollutants.
AB  - Infiltration systems are widely used to manage stormwater in urban areas but
      questions about their long term sustainability need to be addressed. The possible
      pollution of the groundwater and the concentration of pollutant trapped in the
      soil are of major interest. This article focuses on the concentration of heavy
      metals found in the top layer of an infiltration basin. Two sampling campaigns
      have been undertaken 10 months apart and 200 samples were collected and analysed
      for lead (Pb), zinc (Zn) and copper (Cu). High concentrations were measured at
      the surface of the system; pollutant build up over time is clearly evident,
      especially in the lower lying areas, as well as higher concentrations in the
      oldest part of the system. Finally, the total mass of heavy metals trapped in the
      top layer of the systems are evaluated.

PMID- 18075185
TI  - Hindered and compression settling: parameter measurement and modelling.
AB  - The Vesilind settling velocity function forms the basis of flux theory used both
      in state point analysis (for design and capacity rating) and one-dimensional
      dynamic models (for dynamic process modelling). This paper proposes new methods
      to address known shortcomings of these methods, based on an extensive set of
      batch settling tests conducted at different scales. The experimental method to
      determine the Vesilind parameters from a series of bench scale settling tests is
      reviewed. It is confirmed that settling cylinders must be slowly stirred in order
      to represent settling performance of full scale plants for the whole range of
      solids concentrations. Two new methods to extract the Vesilind parameters from
      settling test series are proposed and tested against the traditional manual
      method. Finally, the same data set is used to propose an extension to one
      dimensional (1-D) dynamic settler models to account for compression settling.
      Using the modified empirical function, the model is able to describe the batch
      settling interface independently of the number of layers.

PMID- 18075186
TI  - Reuse of carwash wastewater with hollow fiber membrane aided by enhanced
      coagulation and activated carbon treatments.
AB  - The particles from carwash wastewater were separated by a hollow fiber membrane
      aided by a enhanced coagulation and activated carbon. This study demonstrated
      that the addition of KMnO(4) to coagulant (PAC) could enhance the efficiency of
      coagulation, which helped reduce clogging of the ultrafiltration membrane and
      activated carbon. The existence of LAS can loosen the gel layer on the membrane
      and improve the flux. Adsorption of particles such as organic matter and oil is
      the main reason causing membrane flux decrease. When carwash wastewater was
      pretreated, the permeation flux of membrane showed a higher value. LAS, odour and
      colour are removed by GAC adsorption treatment at last. The COD, BOD, LAS and oil
      of reuse water was 33.4 mg/L, 4.8 mg/L, 0.06 mg/L and 0.95 mg/L, respectively.

PMID- 18075187
TI  - Elimination of micropollutants and hazardous substances at the source in the
      chemical and pharmaceutical industry.
AB  - Industrial wastewater, especially from chemical and pharmaceutical production,
      often contains substances that need to be eliminated before being discharged into
      a biological treatment plant and following water bodies. This can be done within
      the production itself, in selected waste water streams or in a central treatment
      plant. Each of these approaches has certain advantages and disadvantages.
      Furthermore, a variety of wastewater treatment processes exist that can be
      applied at each stage, making it a challenging task to choose the best one in
      economic and ecological terms. In this work a general approach for that and
      examples from practice are discussed.

PMID- 18075188
TI  - N-nitrosodimethylamine formation during treatment with strong oxidants of
      dimethylamine containing water.
AB  - The aim of the paper is the evaluation of the possibility of NDMA formation, as a
      result of strong oxidants reacting with DMA. Summarized results of investigations
      on N-nitrosodimethylamine formation as a result of dimethylamine reactions with
      chlorine dioxide, ozone and hydrogen peroxide are presented. Preliminary results
      of experiments on NDMA formation as a result of DMA reactions with permanganate
      are also shown. The experiments on dimethylamine reactions with chlorine dioxide,
      hydrogen peroxide and permanganate were carried out at room temperature under
      static conditions. Ozonation experiments were carried out at room temperature in
      a semi-continuous mode. Water samples from all experiments described above were
      collected during the experiment itself and subsequently analyzed with HPLC-IE
      with UV-Vis detector at 230 nm. NDMA formation was also confirmed by GC-LRMS.
      NDMA forms as a result of chlorine dioxide, ozone, hydrogen peroxide or
      permanganate reactions with dimethylamine. both in the presence as well as in the
      absence of ammonia ions. The presence of nitrites and nitrates in a post-reaction
      mixture suggests that NDMA are formed as the result of DMA reactions with
      nitrites. Thus the mechanism of NDMA formation with these oxidants is different
      than that described by Mitch et al. and Choi et al. The results also showed a
      conversion ratio of DMA to NDMA of even up to a single percent (with relation to
      amines), a simultaneous decrease of NDMA formation potential with a decrease of
      pH, however, in the case of chlorine dioxide application, a maximum conversion
      ratio was observed, as well the NDMA formation potential is strongly dependent on
      the oxidant/DMA ratio.

PMID- 18075189
TI  - Occurrence of 70 pharmaceutical and personal care products in Tone River basin in
      Japan.
AB  - The occurrence of 70 pharmaceutical and personal care products (PPCPs) was
      investigated in the Tone River. The river has the largest basin in Japan, and the
      water is utilized not only for farming, but also as a source of water supply. One
      day in both January and October 2006, surface waters in the river and its
      tributaries and effluents from sewage treatment plants (STPs) directly
      discharging into the Tone River were collected, the location of which ranged over
      150 km along the river. The 70 PPCPs in the samples were concentrated by solid
      phase cartridge and were measured by LC-MS/MS using three analytical methods.
      Fifty-seven PPCPs were detected in one or more samples. Bezafibrate, caffeine,
      carbamazepine, clarithromycin, crotamiton and sulpiride were frequently detected.
      Mass flow profiles of some PPCPs (e.g., crotamiton) were comparable to cumulative
      inhabitants in the basin, suggesting that these PPCPs could be markers of
      population. Total load of each PPCP into the basin from upstream, the
      tributaries, and the STPs were calculated. The contribution of selected PPCPs
      from the tributaries with lower sewerage system coverage was dominant compared to
      those from upstream and the STPs, suggesting the installation of sewerage systems
      is necessary to reduce the load of PPCPs in the Tone River basin.

PMID- 18075190
TI  - Monitoring, removal and risk assessment of cytostatic drugs in hospital
      wastewater.
AB  - Cytostatic agents are applied in cancer therapy and subsequently excreted into
      hospital wastewater. As these substances are known to be carcinogenic, mutagenic
      and toxic for reproduction, they should be removed from wastewater at their
      source of origin. In this study the fate and effects of the cancerostatic
      platinum compounds (CPC) cisplatin, carboplatin, oxaliplatin, 5-fluorouracil (5
      FU) and the anthracyclines doxorubicin, daunorubicin and epirubicin were
      investigated in hospital wastewater. Wastewater from the in-patient treatment
      ward of a hospital in Vienna was collected and monitored for the occurrence of
      the selected drugs. A calculation model was established to spot the correlation
      between administered dosage and measured concentrations. To investigate the fate
      of the selected substances during wastewater treatment, the oncologic wastewater
      was treated in a pilot membrane bioreactor system (MBR) and in downstream
      advanced wastewater treatment processes (adsorption to activated carbon and UV
      treatment). Genotoxic effects of the oncologic wastewater were assessed before
      and after wastewater treatment followed by a risk assessment. Monitoring
      concentrations of the selected cytostatics in the oncologic wastewater were in
      line with calculated concentrations. Due to different mechanisms (adsorption,
      biodegradation) in the MBR-system 5 - FU and the anthracyclines were removed <
      LOD, whereas CPC were removed by 60%. In parallel, genotoxic effects could be
      reduced significantly by the MBR-system. The risk for humans, the aquatic and
      terrestrial environment by hospital wastewater containing cytostatic drugs was
      classified as small in a preliminary risk assessment.

PMID- 18075191
TI  - Pulmonary inflammation in brown Norway rats: possible association of
      environmental particles in the animal room environment.
AB  - Brown Norway (BN) rats have been found to develop granulomatous pneumonia with
      high spontaneous incidence under normal husbandry conditions. In our laboratory,
      ambient particles from the animal housing environment were suspected to be
      involved in the pathogenesis of these pulmonary lesions. In the present study, we
      correlated the histopathology of spontaneous granulomatous pneumonia with the
      cytology of bronchoalveolar lavage fluid (BALF) analysis and animal room particle
      counts. The results show that the sum of the macroscopic lesion score in the lung
      correlated with the number of eosinophils in the BALF. Microscopically, the
      severity of granulomatous lesions was significantly correlated with both
      pulmonary eosinophils and the number of eosinophils in the BALF, but not with
      those of neutrophils or lymphocytes. In addition, the histological features of
      the lesions were not influenced by housing conditions or sensitization with
      ovalbumin. Ambient particles (0.3-1.0 microm in diameter) in the animal room
      environment were measured and compared with the number of eosinophils in BALF.
      Interestingly, there was a significant correlation between them, suggesting a
      possible relationship between environmental particles and the pathogenesis of
      granulomatous pneumonia in BN rats. However, further study is needed to clarify
      the pathogenic mechanism.

PMID- 18075192
TI  - Histocompatible chicken inbred lines: homogeneities in the major
      histocompatibility complex antigens of the GSP, GSN/1, PNP/DO and BM-C inbred
      lines assessed by hemagglutination, mixed lymphocyte reaction and skin
      transplantation.
AB  - Chicken inbred lines of the GSP, GSN/1, PNP/DO and BM-C have been established by
      selection of a specific allele at the B blood group locus (MHC B-G region) and
      other polymorphic loci through pedigree mating. To extend the potential of these
      inbred lines as experimental animals in Aves, we assessed the antigenic
      homogeneities of the MHC antigens by three immunological methods. Antigenic
      variations of red blood cells (RBCs) were surveyed in the inbred lines and a
      random-bred line (NG) derived from the Nagoya breed by using ten kinds of intact
      antisera produced in the inbred line of chickens against RBCs of a red junglefowl
      and hybrids. In the hemagglutination test, no individual variations were found
      within the inbred line at all, while all the ten antisera detected highly
      heterogeneous reactions in individuals of the NG. The reciprocal one-way mixed
      lymphocyte reactions gave constantly higher stimulation responses (P<0.01)
      between individual pairs from the inbred lines having different B alleles
      compared to pairs within the inbred line, while lower stimulation was observed
      between pairs of the GSP and GSN/1 inbred lines both having the B(21) allele. In
      reciprocal skin transplantation, the transplanted skingrafts within the inbred
      line and between individuals from the GSP and GSN/1 inbred lines survived more
      than 100 days, while all the skingrafts showed signs of rejection within 7 days
      among the inbred lines having different B alleles. The results obtained by the
      three practical methods coincidentally indicated that the individuals in the
      respective four inbred lines were histocompatible, and further, that the GSP and
      GSN/1 individuals were histocompatible.

PMID- 18075194
TI  - Experimental adhesion model: effect of viscosities of fluids put in the
      peritoneal cavity on preventing peritoneal adhesions.
AB  - In this study we assessed the effectiveness of fluid viscosities placed in the
      peritoneal cavity to prevent postoperative peritoneal adhesions. Thirty-six
      Wistar albino female rats (average weight: 160 +/- 30 g, average age: 6.5 months)
      were divided into three groups of equal number. A standard adhesion pattern was
      formed in each group. Then, 3 ml isotonic sodium chloride solution (relative
      viscosity value: 1) was added into the peritoneal cavity of group 1; 3 ml
      standard 6% hydroxy ethyl starch solution (HES) (relative viscosity value: 2.9)
      was added into the peritoneal cavity of group 2; and a standard HES solution that
      was concentrated by dehydration (relative viscosity value: 249.7) was added into
      the peritoneal cavity of group 3. All rats were sacrificed on postoperative day
      10 and the adhesions that formed were graded. In group 1, grade-3 adhesions
      developed in 9 (75%) rats, and grade-2 developed in 3 (25%) rats. In group 2,
      grade-3 adhesions developed in 1 (8.3%) rat, grade-2 developed in 6 (50%) rats,
      and grade-1 developed in 5 (41.6%) rats; in group 3, grade-3 adhesions developed
      in 9 (75%) rats, and grade-2 developed in 3 (25%) rats. The adhesion scores of
      group 3 and group 1 were equal to each other (P=1), while the adhesion score of
      group 2 was significantly less (chi(2): 18.23, P<0.001). Increasing the viscosity
      of fluids that are inserted in the peritoneal cavity may reduce the formation of
      postoperative peritoneal adhesions till a critical value of unknown viscosity is
      achieved. The mechanism behind this process remains unclear.

PMID- 18075193
TI  - Differential cardiovascular effects of endotoxin derived from Escherichia coli or
      Pseudomonas aeruginosa.
AB  - Sepsis is characterized by various symptoms, signs and underlying
      pathophysiology. To investigate possible mechanisms underlying this diversity, we
      compared the cardiovascular effects of lipopolysaccharide (LPS) derived from
      Escherichia coli (E-LPS) with those of LPS from Pseudomonas aeruginosa (P-LPS) in
      rats. We also examined the possible roles of tumor necrosis factor-alpha (TNF
      alpha) and oxidative stress in LPS-induced cardiovascular damage. E-LPS (10 mg/kg
      body weight) or P-LPS (2 mg/kg body weight) was administered intravenously to
      Wistar rats. Echocardiography was serially performed. E-LPS induced an increase
      in left ventricular fractional shortening that persisted for at least 6 h,
      whereas P-LPS elicited an initial increase and a subsequent decrease in this
      parameter. Histological analysis revealed that P-LPS induced interstitial edema,
      congestion, intramyocardial bleeding, myocardial necrosis, infiltration of
      inflammatory cells, and formation of fibrin thrombi in the heart, whereas no
      pathological changes were apparent in the hearts of rats treated with E-LPS.
      Furthermore, the plasma concentration of TNF-alpha in rats treated with P-LPS was
      greater than that in rats treated with E-LPS, but the glutathione redox ratio in
      the heart was not affected by either type of LPS. In conclusion, E-LPS and P-LPS
      induced distinct patterns of functional and structural responses in the
      cardiovascular systems of rats. These differential responses may be attributable
      in part to the difference in the associated increases in the plasma concentration
      of TNF-alpha. The cardiovascular effects of LPS thus depend on the causative
      organisms.

PMID- 18075195
TI  - Effect of insulin therapy on renal changes in spontaneously diabetic Torii rats.
AB  - The spontaneously diabetic Torii (SDT) rat has recently been established as an
      animal model of non-obese type 2 diabetes, in which ocular complications severe
      occur. However, the function and morphological features of the diabetic renal
      lesions in SDT rats have not been reported in detail. Therefore, we evaluated
      changes over time in renal lesions in SDT rats. In addition, SDT rats were
      treated with insulin to observe whether these renal complications are caused by
      hyperglycemia. Renal functional parameters and renal lesions were monitored in
      SDT rats from 8 to 68 weeks of age. Sprague-Dawley (SD) rats of similar age were
      used as control animals. In the insulin-treated group of SDT rats, insulin
      pellets were implanted at 24 weeks of age to compare the development of renal
      lesions. The SDT rats began to develop hyperglycemia at 20 weeks of age. In the
      histopathological examination of the kidney, glycogen deposition of the renal
      tubular epithelium and renal tubular dilation were observed from 24 weeks of age
      in the untreated SDT rats, and the changes in the renal tubules markedly
      progressed with aging. Moreover, thickening of the glomerular basement membrane
      was observed from 32 weeks of age. At 50 weeks of age, the glomeruli showed
      increase of mesangial matrix, with predominantly diffuse lesions showing by 68
      weeks of age. The mesangial proliferation gradually progressed. In the SD rats,
      no renal lesions were present at 50 and 68 weeks of age. SDT rats with insulin
      treatment remained normoglycemic throughout observation and their renal
      functional parameters were normal. Glycemic control in SDT rats prevented the
      development of renal lesions. The features of SDT rats indicate their usefulness
      as an animal model for investigating diabetic nephropathy.

PMID- 18075196
TI  - Evaluation of bedding and nesting materials for laboratory mice by preference
      tests.
AB  - Bedding and nesting materials can improve the health and environmental welfare of
      laboratory mice. This study was carried out to examine which items are actually
      preferred by mice. Two series of studies were performed on four types of floor
      covering materials (Wood-shavings (Clean-chip), Cloth (Agrebe), Recycled-paper
      (Paper-clean), Paper (Care-feeaz), and on four types of nesting materials
      (Recycled-paper (Shepherd-shack), Cloth (Agrebe), Wood (Wood-cylinder), and
      Polycarbonate (Mouse-igloo). Preference of bedding materials was judged by the
      time length of staying in a cage. The results indicate that mice stayed in the
      cloth material (Agrebe) longer than in other bedding materials (light 51.1 +/-
      5.3%, dark 51.5 +/- 2.6%). In the second experiment, the duration of stay in
      Agrebe was significantly longer than that in the other nesting materials in the
      light phase (70.9 +/- 2.4%). In the dark phase, staying time both in Agrebe and
      Shepherd-shack were significantly longer. These data suggest that cloth bedding
      and nesting is recommended for the environmental enrichment of laboratory mice.

PMID- 18075197
TI  - Skin morphology of the Clawn miniature pig.
AB  - Skin morphology of the Clawn miniature pig (CMP) was investigated at the axilla,
      medial thigh, back and loin. The mean thickness of the epidermis (excluding the
      corneal layer), the mean number of layers of keratinocytes comprising the
      epidermis and the mean height of keratinocytes were assessed morphometrically.
      When observed under a light microscope, the skin of the CMP resembled human skin.
      Morphometrically, skin from the back and loin of the CMP most resembles human
      skin. Electron microscopic observations revealed sparse but typical Birbeck
      granules in the epidermal Langerhans cells of the CMP. The results of the present
      study indicate that CMP skin is potentially useful as a model for human skin.

PMID- 18075198
TI  - Characteristics and gender differences concerning pulmonary hemodynamics in Clawn
      miniature pigs.
AB  - The characteristics and gender differences of the pulmonary hemodynamic
      parameters of 16 Clawn miniature pigs were examined and the data were compared
      with reports concerning dogs and other pig species. The pulmonary systolic,
      diastolic and mean arterial blood pressures of the mini-pig were slightly higher
      than those of the dog, respectively, but both the right atrial pressure and
      pulmonary capillary wedge pressure were within the normal physiological ranges of
      the dog. Concerning gender differences in hemodynamic parameters of the mini-pig,
      the female values, except the right atrial pressure, were slightly higher than
      those of the male, but no significant differences were recognized. The present
      study results will help pulmonary researchers understand the differences between
      Clawn miniature pigs and dogs for accurate analysis of experimental results.

PMID- 18075199
TI  - Spontaneous adenocarcinoma immunoreactive to cyclooxygenase-2 and transforming
      growth factor-beta1 in the buccal salivary gland of a Richardson's ground
      squirrel (Spermophilus richardsonii).
AB  - The ground squirrel is used as an experimental animal because of its unique
      biological nature. A 3-year-old female Richardson's ground squirrel developed a
      mass, 1.5 cm in diameter, in the buccal mucosa. The mass consisted of neoplastic
      epithelial cells showing acinar, ductular, intraductal papillary, solid, and
      lobular growth patterns; the cells were immunoreactive to cytokeratin,
      cyclooxygenase-2 (a marker of malignancy) and TGF-beta1. After resection, the
      tumor recurred with increased area having a solid or lobular pattern with little
      differentiation. This tumor was diagnosed as an adenocarcinoma arising from the
      buccal gland, the first case reported in the ground squirrel. A prominent
      desmoplastic reaction was present. The interstitial cells reacted to alpha-smooth
      muscle actin and vimentin, indicating a myofibroblastic nature, presumably
      induced by epithelial TGF-beta1.

PMID- 18075200
TI  - An optimal embryo transfer condition for the effective production of DBA/2J mice.
AB  - The DBA/2J mouse strain is a standard laboratory strain that is widely used for
      biomedical research. This strain, however, suffers from poor reproductive
      performance. In addition, the conditions for reliable embryo transfer (ET) of
      this strain have not been elucidated. The intention of this study was to
      determine the optimal number of embryos for transfer that allow the effective
      production of DBA/2J offspring. In the experiment, 7 to 15 embryos per oviduct
      were transferred into pseudopregnant ICR females. A relatively high success rate
      for pup production was observed when a large number of DBA/2J embryos (30 embryos
      per female) were transferred. This result shows that the ET efficiency of the
      DBA/2J strain can be improved by increasing the number of transferred embryos.

PMID- 18075201
TI  - Mapping of jog locus to the region between D6Mit104 and D6Mit336 on mouse
      chromosome 6.
AB  - The joggle mouse is a recessive ataxic mutant carrying an unknown mutation in a
      C3H/He (C3H)-derived chromosomal segment. Taking advantage of the mouse genome
      database, we selected 127 DNA microsatellite markers showing heterozygosity
      between C3H and C57BL/6J (B6) and a first round of screening for the joggle
      mutation was performed on B6-jog/+ partial congenic mice (N4). We identified 4
      chromosomal regions in which 13 microsatellite markers show heterozygosity
      between C3H and B6. Then, we analyzed the genotype of these 4 chromosomal regions
      in mice that showed the joggle phenotype and mapped the jog locus between markers
      D6Mit104 (111.4 Mb) and D6Mit336 (125.1 Mb) (an interval of 13.7 Mb) on
      chromosome 6. By using a partial congenic strain together with the mouse genome
      database, we successfully mapped the chromosomal localization of the jog locus
      much more efficiently than by conventional linkage analysis.

PMID- 18075202
TI  - Testicular development in growth-retarded mice.
AB  - To assess delayed fertility in male growth-retarded (grt) mice with congenital
      primary hypothyroidism, their testes were chronologically examined. The
      testicular weight in grt mice was significantly lower than age-matched normal
      mice until 8 weeks but was comparable at 13 and 26 weeks. While normal mice had
      mature sperm cells in both testes and epididymides at 5 weeks, age-matched grt
      mice did not. The size of the seminiferous tubules in testes of grt mice was
      smaller than that of normal mice before 13 weeks but was comparable at 26 weeks.
      These findings suggest that male grt mice might need more than 13 weeks to
      develop mature testes.

PMID- 18075203
TI  - Effect of chronic topical exposure to low-dose noxious chemicals and stress on
      skin sensitivity in mice.
AB  - It has been suggested that the recent increase in inflammatory diseases is
      related to an increase in environmental chemicals and psychiatric stress. To
      investigate the effect of chronic topical exposure to chemicals and isolation
      stress, low-dose formalin (a mild contact sensitizer and an irritant), 2,4,6
      trinitrochlorobenzene (TNCB; a potent contact sensitizer) and sodium lauryl
      sulphate (SLS; an irritant) were applied to mouse ears at 7-d intervals under no
      stress or stress conditions. Skin reactions (ear swelling) elicited by formalin
      and TNCB increased time dependently. At the chronic stage, a significant skin
      reaction peaking at 1 h after application was elicited on the formalin-treated
      sites, while a shift from a delayed-type hypersensitivity to an immediate-type
      response was observed on the TNCB-treated sites. At the formalin-treated sites,
      genes related to neurogenic inflammation, i.e., bradykinin (BK) B2 receptor, IL
      6, and membrane metallo endopeptidase (NEP) mRNA were upregulated. In the TNCB
      treated sites, marked upregulation of IFN-gamma, IL-1beta, IL-4, and IL-6 mRNA
      was observed in addition to B2 receptor mRNA. Pretreatment with HOE140, the B2
      receptor antagonist suppressed these skin reactions. Increased skin sensitivity
      to an unrelated chemical, ethanol, and thermal stimuli were elicited in formalin
      and TNCB-treated mice. Cortisol levels in formalin-treated mice and IgE levels in
      TNCB-treated mice were elevated respectively. Stress markedly amplified the skin
      reactions and gene expression related to neurogenic inflammation. SLS did not
      induce any changes. It was concluded that chronic topical exposure to low-dose
      noxious chemicals and stress could easily induce skin sensitivity relating to the
      BK-B2 pathway and nociceptive sensitization reflecting neural sensitization.

PMID- 18075204
TI  - Association of smoking behavior and socio-demographic factors, work, lifestyle
      and mental health of Japanese civil servants.
AB  - Few studies have examined the individual and social impact of smoking behavior in
      the Japanese population. The purpose of this study was to clarify the association
      between smoking behavior and socio-demographic factors, lifestyle, mental health
      and work characteristics of Japanese civil servants. A self-administered
      questionnaire survey of 1,439 employees (821 men and 618 women) aged 20-64 yr was
      conducted in a local government department in 2001. The questionnaire included
      items on socio-demographic factors, education level, grade of employment,
      lifestyle, affect balance scale, and work characteristics. Smoking status was
      divided into current smoker, ex-smoker and never smoked. Multiple logistic
      regression analysis was performed to evaluate the relationship between smoking
      and the other items. Men presented a higher smoking prevalence rate than women
      (53.1% vs. 4.9%). In men, a strong relationship between current smoker and
      advanced age (40 yr or older), low education level, less physical activity,
      irregular breakfast and negative affect balance was found. Among men with a low
      education, the prevalence of smoking cessation was significantly lower in
      comparison to men with a high education. In women, being young (20-29 yr),
      unmarried (single or other), having a hobby, and irregular breakfast were
      associated with smoking behavior. Furthermore, smoking cessation was
      significantly associated with having a hobby and negative affect balance. The
      above results suggest that socio-demographic, lifestyle and mental health
      characteristics are independently associated with current smoking. These factors
      should be considered in smoking cessation policies as program components.

PMID- 18075205
TI  - Development of Japanese version of the checklist individual strength
      questionnaire in a working population.
AB  - The aims of the present study were to develop and validate the Japanese version
      of the checklist individual strength questionnaire (CIS) which is used to measure
      prolonged fatigue not only in the general population but also in the working
      population. We obtained permission to use CIS from its author and translated the
      questionnaire into Japanese. Then, the Japanese version of the questionnaire was
      translated back into English by a bilingual person. The author of the original
      version agreed that the back-translated version was conceptually and
      linguistically equivalent to the original CIS. To validate CIS, 399 workers
      (66.7% were men) from different companies answered the Japanese version of the
      CIS (CIS-J), Maslach burnout inventory-general survey (MBI-GS), Beck Depression
      Inventory-II (BDI-II), visual analogue scale (VAS) questionnaires for subjective
      fatigue, number of overtime hours and number of hours of sleep. Cronbach's alpha
      for the total CIS-J score was 0.91. The test-retest reliability assessed with an
      intra-class correlation coefficient was 0.82. Although confirmatory factor
      analysis did not show an ideal model fit, the correlation coefficients between
      the total CIS score and the MBI-GS exhaustion score, the BDI-II score and the VAS
      score were 0.58 (p<0.01), 0.66 (p<0.01) and 0.63 (p<0.01), respectively. The less
      workers slept and the longer they worked, the higher their total CIS score
      became. CIS-J showed good reliability and acceptable validity in the working
      population. Thus, it could be useful for studying fatigue among Japanese working
      populations.

PMID- 18075206
TI  - Predisposing factors of sleep-disordered breathing in Japanese male workers.
AB  - The aim of this study was to elucidate the usable predisposing factors of sleep
      disordered breathing (SDB) in the workplace. A total of 353 male workers who
      complained of SDB related symptoms such as witnessed snoring, recurrent awakening
      from sleep, urination during the night, morning headache, and excessive daytime
      sleepiness were included in the analysis. We examined hyoid-mental distance
      (HMD), modified Mallampati score (MMS), and the narrowness of the pharynx with
      tonsillar hypertrophy as the predisposing physical findings of SDB. We used the
      number of 3% or more oxygen desaturation events per hour (ODI3) as the indicator
      of SDB. The mean values (S.D.) of all subjects were 44.3 (8.9) yr (19-66 yr) of
      age, and 25.9 (3.8) Kg/m(2) body mass index (BMI). A significant difference in
      ODI3 was found between the HMD classes, and also between the subjects with and
      without tonsillar hypertrophy. Mean ODI3 adjusted for age, BMI, and alcohol
      consumption on the day of monitoring was high in the group of short HMD and the
      group of tonsillar hypertrophy (+). For MMS, though ODI3 did not appear to be
      significantly different, mean ODI3 was high in the MMS-IV. In conclusion, short
      HMD and tonsillar hypertrophy are the important findings predicting SDB
      identified by pulse oximetry. These findings would be beneficial in the workplace
      for selection of subjects who should be encouraged to undergo pulse oximetry for
      detection of SDB.

PMID- 18075207
TI  - Association of work-related factors with psychosocial job stressors and
      psychosomatic symptoms among Japanese pediatricians.
AB  - A cross-sectional study was conducted to explore what work-related factors were
      associated with job stress among pediatricians in Japan, as determined by the
      demand-control-support model and psychosomatic symptoms. We sent an anonymous
      questionnaire to a random sample of 3,000 members selected from the nationwide
      register of the Japan Pediatric Society and received 850 responses (response
      rate, 28%). Data from the 590 respondents who worked more than 35 h per week as a
      pediatrician and had no missing responses in the questionnaire were analyzed. We
      measured workload-related variables (e.g. working hours, work schedule) and
      recovery-related variables (e.g. workdays with no overtime, days off with no work
      in the past month) as exposure variables, and psychosocial job stressors (the
      Brief Job Stress Questionnaire) and psychosomatic symptoms as outcome variables.
      Longer working hours per week was significantly associated with greater job
      demand, lower job control and more psychosomatic symptoms (p<0.05). After
      adjusting for working hours, more workdays with no overtime was significantly
      associated with lower job demand, greater job control and fewer psychosomatic
      symptoms (p<0.05). Our findings suggest that long working hours is a risk factor
      for job stressors and psychosomatic symptoms, and that workdays with no overtime
      is a protective factor which may facilitate recovery. Controlling working hours
      and encouraging non-overtime workdays may be important for reducing job stressors
      and psychosomatic symptoms among pediatricians in Japan.

PMID- 18075208
TI  - Evaluation of the control banding method--comparison with measurement-based
      comprehensive risk assessment.
AB  - The control banding method, or "control banding", is a simplified risk assessment
      system for chemical handling tasks. This system is supposed to provide assessment
      results of reasonable quality without expert involvement. The objective of this
      study was to evaluate the appropriateness of control banding judgment on the
      basis of workplace safety. A common approach for assessing workplace risk, which
      is called "comprehensive risk assessment" in this study, is to measure workers'
      exposure and compare it with relevant occupational exposure limits. Risk
      assessment was performed with control banding (COSHH Essentials, UK) at 12
      workplaces of a petroleum company in Japan, where health risks had already been
      assessed separately through comprehensive risk assessment by experts and control
      technologies implemented accordingly. The obtained control banding judgments were
      then examined with regard to their adequacy by comparing them with existing
      control technologies. There was majority of cases (seven) where judgments by
      control banding were identified as "over-controlled"; there was no judgments
      identified as "under-controlled". Control banding also requested the seeking of
      expert advice in the majority of cases (eight). Thus, it was demonstrated that
      control banding tends to provide safe-sided judgment. A possible interpretation
      of this is that control banding is inherently designed to secure workplace safety
      by compensating for its insufficient exposure information with safe-sided
      judgment criteria and by requiring experts' intervention in high-risk cases.
      Control banding could be widely and effectively utilized in Japan, especially by
      employers in small enterprises, provided that the above characteristics are pre
      acknowledged and health experts are made available. To this aim, it is essential
      to develop new local health experts and establish institutional mechanisms for
      facilitating employers' access to expert advice. It should however be noted that
      the number of workplaces evaluated in this study was small.

PMID- 18075209
TI  - Use of field-portable X-ray fluorescence (FPXRF) analyzer to measure airborne
      lead levels in Korean workplaces.
AB  - We evaluated the possibility of applying field-portable x-ray fluorescence
      (FPXRF) analysis as a rapid, on-site and near real-time method for evaluating
      airborne lead contamination in Korean workplaces. A total of 287 airborne lead
      filter samples were measured in 12 lead-using workplaces during routine
      industrial hygienic monitoring procedures as required by Korean government
      regulations. All filter samples were collected using the standard industrial
      hygiene sampling protocol described in NIOSH Method 7300 using closed-face 37-mm
      cassettes with preloaded cellulose ester membrane filters with a pore size of 0.8
      microm. The samples were first analyzed using the non-destructive, FPXRF
      analytical method (NIOSH method 7702), and then subsequently analyzed using
      inductively coupled plasma atomic emission spectrophotometry (ICP) (NIOSH method
      7300) as a reference analytical method. Pair-wise comparison of filter samples
      using the paired t-test revealed no statistically significant differences between
      the two methods over a wide range of airborne lead levels (0.018-0.201
      microg/m(3)) either over the industries assessed or separately in the 12 lead
      using workplaces. Linear regression of the data between the ICP and FPXRF methods
      produced a slope of 1.03, a y-intercept of 0.13 microg/sample, and a coefficient
      of determinant (r(2)) of 0.975 for all the data. For samples in the range from 0
      to 100 microg, the corresponding values were 1.07, -1.20 microg/sample, and
      0.925, respectively. There were no significant differences in the regression
      analyses of the three industry types (r(2)=0.964-0.982). Our data suggest that
      FPXRF data are highly correlated with those from the laboratory-based ICP method
      in terms of accuracy, precision, and bias. Therefore, FPXRF can be used for the
      rapid, on-site analysis of lead air-filter samples for values up to 26
      microg/sample prior to laboratory confirmation by the ICP method.

PMID- 18075210
TI  - Pilot study of a dissection table for gross anatomy laboratory equipped with a
      photocatalytic device that decomposes formaldehyde.

PMID- 18075211
TI  - Teledermatology--a hitherto underestimated tool in occupational medicine-
      indications and limitations.

PMID- 18075213
TI  - Poor mental health associated with job dissatisfaction among school teachers in
      Japan.
AB  - School teaching is regarded as a stressful occupation. The present study aimed to
      compare the likelihood of having minor psychiatric disorders (MPD) among school
      teachers with that among civil servants, and to investigate what factors were
      specifically associated with MPD in teachers. We conducted a questionnaire-based
      survey of 403 teachers employed at state schools and 611 civil servants as a
      comparison group in a medium-sized city in Japan. The response rate was 59.6% for
      teachers and 62.0% for civil servants. Mental health was assessed using the 28
      item General Health Questionnaire (GHQ-28), according to which those with a score
      of six or higher were considered to have MPD. Logistic regression analysis was
      used to identify the factors associated with MPD. Although the proportion of
      subjects with MPD among teachers was greater than that among civil servants, the
      difference in the proportion was not statistically significant in the multiple
      logistic regression analysis adjusted for potential confounders. In a separate
      analysis of the teachers, reduced job satisfaction and shorter time spent of
      leisure were significantly associated with an increased likelihood of having MPD.
      In the group of civil servants, longer working hours, reduced life satisfaction,
      a history of sick leave, and physical illness were associated with an increased
      likelihood of having MPD. When this analysis was conducted separately for male
      and female teachers, job dissatisfaction alone was associated with MPD only in
      female teachers. Poor mental health of Japanese school teachers, female teachers
      in particular, was found to be associated with job dissatisfaction.

PMID- 18075212
TI  - Biological monitoring of pyrethroid exposure of pest control workers in Japan.
AB  - Synthetic pyrethroids such as cypermethrin, deltamethrin and permethrin, which
      are usually used in pest control operations, are metabolized to 3-phenoxybenzoic
      acid (3-PBA) and excreted in urine. Though 3-PBA can be used to assess exposure
      to pyrethroids, there are few reports describing urinary 3-PBA levels in Japan.
      This study aimed to investigate the seasonal variation of the exposure levels of
      pyrethroids and the concentration of urinary 3-PBA among pest control operators
      (PCOs) in Japan. The study subjects were 78 and 66 PCOs who underwent a health
      examination in December 2004 and in August 2005, respectively. 3-PBA was
      determined using gas chromatography-mass spectrometry. The geometric mean
      concentration of urinary 3-PBA in winter (3.9 microg/g creatinine) was
      significantly lower than in summer (12.2 microg/g creatinine) (p<0.05). Geometric
      mean concentrations of urinary 3-PBA in the spraying workers and the not-spraying
      workers within 2 d before the survey were 5.4 microg/g creatinine and 0.9
      microg/g creatinine for winter with a significant difference between the groups
      (p<0.05), and 12.3 microg/g creatinine and 8.7 microg/g creatinine for summer
      (p>0.05), respectively. A significant association of 3-PBA levels and pyrethroid
      spraying was thus observed only in winter. In conclusion, the results of the
      present study show that the exposure level of pyrethroids among PCOs in Japan
      assessed by monitoring urinary 3-PBA was higher than that reported in the UK but
      comparable to that in Germany. Further research should be accumulated to
      establish an occupational reference value in Japan.

PMID- 18075214
TI  - Associations of excessive sleepiness on duty with sleeping hours and number of
      days of overnight work among medical residents in Japan.
AB  - Despite long-standing concerns regarding the effects of working hours on the
      performance and health of medical residents, and the patients' safety, prior
      studies have not shown an association of excessive sleepiness with the number of
      sleeping hours and days of overnight work among medical residents. In August
      2005, a questionnaire was mailed to 227 eligible participants at 16 teaching
      hospitals. The total number of sleeping hours in the last 30 d was estimated from
      the average number of sleeping hours during regular days and during days with
      overnight work, and the number of days of overnight work. Multiple logistic
      regression analysis was used to adjust for potentially associated variables. A
      total of 149 men and 47 women participated in this study. The participation rate
      was 86.3%. Among the participants, 55 (28.1%) suffered from excessive sleepiness.
      Excessive sleepiness was associated with sleeping for less than 150 h in the last
      30 d (corrected odds ratio [cOR]=1.57; 95% confidence interval [CI], 1.02-2.16).
      The number of days of overnight work in the last 30 d showed no association with
      excessive sleepiness. Excessive sleepiness was also associated with smoking (cOR,
      1.65; 95%CI, 1.01-2.32). Medical residents who slept for less than 150 h in the
      last 30 d and smoked had a significantly higher risk of excessive sleepiness on
      duty.

PMID- 18075215
TI  - Knowledge, attitude and practices related to occupational health problems among
      garment workers in Tamil Nadu, India.
AB  - The garment manufacturing process is a labour intensive task. The workers in this
      are employed in three different sections namely cutting, stitching and finishing.
      As these workers perform repetitive tasks throughout the workday, they face
      several work related problems. The aim of this study was to assess the level of
      awareness of health problems among garment workers and their attitudes and
      practices to prevent the same. In a cross-sectional study (n=216) the workers
      employed in the three sections had high levels of knowledge of the health
      problems, but the knowledge of personal protective equipment differed by section.
      More than one half of the workers in all the sections were aware of the benefits
      of personal protective equipment (PPE), but only a few workers in the cutting
      section were using PPE. There was a wide gap between their knowledge level and
      practice with protective devices.

PMID- 18075217
TI  - Preparations and properties of anti-corrosion additives of water-soluble metal
      working fluids for aluminum alloy materials.
AB  - This short review describes various types of anti-corrosion additives of water
      soluble metal working fluids for aluminum alloy materials. It is concerned with
      synthetic additives classified according to their functional groups; silicone
      compounds, carboxylic acids and dibasic acids, esters, Diels-Alder adducts,
      various polymers, nitrogen compounds, phosphoric esters, phosphonic acids, and
      others. Testing methods for water-soluble metal working fluids for aluminum alloy
      materials are described for a practical application in a laboratory.

PMID- 18075218
TI  - Interaction between alpha-linolenic acid-enriched oil and ACE inhibitor
      concerning the decrease in blood pressure in SHR.
AB  - Alpha-linolenic acid (ALA) has been reported to exhibit an antihypertensive
      effect. Angiotensin-converting enzyme inhibitor (ACEI) is also an
      antihypertensive agent. We evaluated the interaction between ALA-enriched oil
      (test oil) and ACEI concerning the decrease in blood pressure by administering
      test oil, ACEI, or test oil + ACEI to 7-week-old spontaneously hypertensive rats
      (SHR). After administration, the systolic pressure decreased significantly in all
      groups compared with the level before administration, but the diastolic pressure
      decreased significantly only in the test oil + ACEI group. No significant
      difference was noted in systolic or diastolic pressure among the 3 groups. These
      results suggest that the interaction between ALA-enriched oil and ACEI is
      limited. Our study suggested the safety of consuming foods containing a large
      amount of ALA in combination with hypotensive agents.

PMID- 18075219
TI  - Large decrease in acute aquatic toxicity of linear alkylbenzene sulfonate in hard
      water and seawater by adding adsorbent.
AB  - LAS (Linear Alkylbenzene Sulphonate) shows relatively high aquatic toxicity in
      hard freshwater or seawater. In this paper, we studied the effect of adsorbent on
      the aquatic toxicity of LAS in hard freshwater and seawater. Daphnia magna and
      Artemia salina were used for acute aquatic toxicity test in freshwater and
      seawater, respectively. Kaolin was used as a model adsorbent and toxic surface
      tension (gamma(tox)) was used as an indicator of toxic condition. Results showed
      that the values of gamma(tox) of LAS to D. magna and A. salina were about 45-55
      mN/m and 35-40 mN/m, respectively. Surface tension of LAS solution decreased and
      its aquatic toxicity increased with increasing the water hardness or the
      salinity. By adding adsorbent into the solutions, the surface activity and the
      aquatic toxicity were decreased greatly, and the effect of water hardness or
      salinity on surface tension and aquatic toxicity were removed. That is to say,
      the surface tension curve of soft freshwater corresponds with that of hard
      freshwater containing adsorbent and the surface tension curve at low salinity
      corresponds with that obtained for high salinity solutions containing the
      adsorbent. Therefore, our experimental data leads to the conclusion that the
      relatively high aquatic toxicity of LAS in concentrated solution of inorganic
      salts disappears in the presence of adsorbents. This is an important viewpoint in
      conducting environmental risk assessment of surfactants.

PMID- 18075220
TI  - [Minimal effective dose on serum cholesterol concentration and the safety
      evaluation of dressing containing plant sterol in Japanese subjects].
AB  - We examined the minimal effective dose on serum cholesterol concentration and the
      safety of dressing containing plant sterol in humans. EXP.1: Sixty-eight healthy
      Japanese males (total cholesterol (TC) > or = 170 mg/dL) were randomly divided
      into four groups, and were given 0, 400, 800 or 1200 mg/day of plant sterol in 15
      g dressing for 4 weeks followed by the washout period of 4 weeks. Although there
      were no significant differences in serum TC and low-density lipoprotein
      cholesterol (LDL-C) concentrations among all groups after feeding plant sterol
      for 4 weeks, in 36 subjects with TC > or = 220 mg/dL, serum LDL-C concentration
      tended to reduce when received 800 or 1200 mg of plant sterol, and the difference
      between 0 and 1200 mg groups was statistically significant. The difference
      between 0 and 800 mg groups was near significant (p=0.053). Intake of 400 mg of
      plant sterol did not change serum LDL-C concentration. EXP.2: Twenty-one healthy
      Japanese subjects (TC > or = 180 mg/dL, 10 men, 11 women) were given 2400 mg/day
      of plant sterol in 45 g dressing for 4 weeks. Clinical data were all remained
      normal. These results indicated that minimal effective dose of the plant sterol
      on serum cholesterol concentration in healthy male subjects is around 800 mg/day,
      and intake of 2400 mg/day of plant sterol is regarded to be safe.

PMID- 18075221
TI  - [Effects of dressing containing plant sterol on serum cholesterol concentration
      and the safety evaluation in borderline or mildly hypercholesterolemic Japanese
      subjects].
AB  - In a placebo-controlled double-blind study, we examined the effects of dressing
      containing plant sterol (PS) on blood lipids and the safety in Japanese
      borderline or mildly hypercholesterolemic subjects. Fifty-nine subjects [total
      cholesterol (TC) concentration > or = 200 mg/dL] were randomly divided into two
      groups and were given daily 15 g of dressing containing 800 mg of PS [PS(+)
      group] or without PS [PS(-)-group] for 12 weeks. Every 4 weeks, fasting blood was
      examined and subjective symptoms were analyzed. Serum TC, low-density lipoprotein
      cholesterol (LDL-C) and apolipoprotein B (ApoB) concentrations did not change in
      the PS(-)-group, while TC and ApoB significantly decreased in the PS(+)-group at
      8 and 12 weeks and LDL-C at 4, 8 and 12 weeks. Moreover, serum TC, LDL-C and ApoB
      concentrations were significantly lower than those of PS(-)-group at 8 and 12
      weeks. Other laboratory tests were all in normal ranges and no adverse events
      were observed. The results indicated that PS-containing dressing decreased serum
      TC, LDL-C and ApoB concentrations in borderline or mildly hypercholesterolemic
      subjects. It is therefore proved that the dressing containing PS is helpful in
      maintaining blood cholesterol level normal and hence, the health of Japanese.

PMID- 18075222
TI  - Preparation and characterisation of protein hydrolysates from Indian defatted
      rice bran meal.
AB  - Rice bran meal is a very good source of protein along with other micronutrients.
      Rice bran meal has been utilized to produce protein isolates and respective
      protein hydrolysates for potential application in various food products. De-oiled
      rice bran meal, available from Indian rice bran oil extraction plants, was
      initially screened by passing through an 80-mesh sieve (yield about 70%). A
      fraction (yield-30%) rich in fibre and silica was initially discarded from the
      meal. The protein content of the through fraction increased from 20.8% to 24.1%
      whereas silica content reduced from 3.1% to 0.4%. Rice bran protein isolate (RPI)
      was prepared by alkaline extraction followed by acidic precipitation at
      isoelectric point. This protein isolate was hydrolysed by papain at pH 8.0 and at
      37 degrees C for 10, 20, 30, 45 and 60 minutes. The peptides produced by partial
      hydrolysis had been evaluated by determining protein solubility, emulsion
      activity index (EAI), emulsion stability index (ESI), foam capacity and foam
      stability (FS). All protein hydrolysates showed better functional properties than
      the original protein isolate. These improved functional properties of rice bran
      protein hydrolysates would make it useful for various application especially in
      food, pharmaceutical and related industries.

PMID- 18075223
TI  - Dimerization of acetoacetamide leading to 5-carbamoyl-4,6-dimethyl-2-pyridone.
AB  - The dimerization of acetoacetamide easily proceeds at room temperature in a
      dimethyl sulfoxide solution to afford 5-carbamoyl-4,6-dimethyl-2-pyridone.

PMID- 18075224
TI  - Formation of W/O microemulsion based on natural glycolipid biosurfactant,
      mannosylerythritol lipid-a.
AB  - Mannosylerythritol lipid-A (MEL-A) is a glycolipid biosurfactant abundantly
      produced from soybean oil by microorganisms at a yield of up to 100 g/L. In this
      study, the formation of water-in-oil (W/O) microemulsion based on the single
      component of MEL-A was confirmed using dynamic light scattering (DLS) and freeze
      fracture electron microscopy (FF-EM). DLS and FF-EM measurements revealed that
      the diameter of the microemulsion increases with an increase in water-to
      surfactant mole ratio (W(0)) ranging from 20 to 60 nm, and the maximum W(0) value
      was found to be 20, which is as high as that of soybean lecithin. Glycolipid
      biosurfactant has a great potential for the formation of W/O microemulsion
      without using any cosurfactants.

PMID- 18075225
TI  - Individual differences in the radiosensitivity of hematopoietic progenitor cells
      detected in steady-state human peripheral blood.
AB  - The aim of this study is to evaluate the individual differences in
      radiosensitivity of lineage-committed myeloid hematopoietic progenitors, colony
      forming cells (CFC), detected in steady-state human peripheral blood (PB).
      Mononuclear cells were prepared from the buffy-coat of 30 individuals PB, and
      were assayed for CFC by semi-solid culture supplemented with cytokines. X
      irradiation was performed in the range of 0.5-4 Gy at a dose rate of about 80
      cGy/min. The mean number of hematopoietic progenitor cells is 5866 alpha 3408 in
      1 ml of buffy-coat, suggesting that the erythroid progenitor cells are the major
      population. The total CFC radiosensitivity parameter D(0) and n value are 1.18
      alpha 0.24 and 1.89 alpha 0.98, respectively. Using a linear regression analysis,
      a statistically significant correlation is observed between the D(0) value and
      the surviving fraction at 4 Gy (r = 0.611 p < 0.001). Furthermore, we evaluate
      the relationship between individual radiosensitivity and the level of
      antioxidants, plasma uric acid, plasma bilirubin, and intracellular glutathione.
      No statistically significant correlations are observed, however, between the D(0)
      parameter and the level of antioxidants, plasma uric acid, plasma bilirubin, and
      intracellular glutathione. The present study demonstrates that there are large
      individual differences in the radiosensitivity of hematopoietic progenitor cells
      as detected in steady-state human PB. These differences demonstrate almost no
      correlation with plasma or intracellular antioxidants. The prediction of
      individual differences in radiosensitivity of CFC can only be measured by 4 Gy
      irradiation.

PMID- 18075226
TI  - Muscularis mucosae - the forgotten sibling.
AB  - Lamina muscularis mucosae sitting beneath mucosal surface of the digestive tract
      has received little attention to date compared with external smooth muscle
      layers. Motor activity of the muscularis mucosae shows a great regional and
      species difference. Autonomic innervation profile is also different from
      esophagus to colon or between animal species. Intracellular transduction
      mechanisms for motor activity of the muscularis mucosae are also different from
      those of external longitudinal and circular muscles or from vascular and airway
      smooth muscles. Since the submucosal area is a major source for eicosanoid
      production, abnormality of muscularis mucosae motor activity may link with
      abnormality of mucosal absorption and secretion functions. Inflammatory bowel
      diseases such as diarrhea, irritable bowel syndrome and Crohn's disease
      accompanied with altered motor activity of the muscularis mucosae. Much attention
      should be attracted to the human muscularis mucosae as a new therapeutic target
      for inflammatory bowel diseases.

PMID- 18075227
TI  - Improvement of gastric motility by hemodialysis in patients with chronic renal
      failure.
AB  - BACKGROUND: Gastrointestinal (GI) symptoms are common in patients with chronic
      renal failure (CRF). We have previously demonstrated that patients with
      predialysis end-stage renal disease showed a high prevalence of GI symptoms and
      gastric hypomotility, and that gastric hypomotility appears to be an important
      factor in generating GI symptoms. However, it is not clear whether impaired
      gastric motor function would improve after hemodialytic treatment. AIMS: To
      examine the relationship between gastric motor function and GI symptoms in CRF
      patients on hemodialysis. METHODS: The study was performed in 19 patients with
      CRF treated with hemodialysis for more than six months and in 12 matched healthy
      controls. GI symptom severity was quantified in all patients. Gastric motility
      was evaluated with cutaneously recorded electrogastrography (EGG) and gastric
      emptying of semi-solid meals using the (13)C-acetic acid breath test. RESULTS:
      Six patients had no symptoms, and 11 had slight GI symptoms with a total symptom
      score of less than 5. Compared with controls, CRF patients revealed no
      differences in gastric motility parameters, with the exception of a lower
      percentage of normogastria in EGG at fasting state. Eleven patients had normal
      gastric motor function (Group A), and eight showed abnormalities of either
      gastric myoelectrical activity or gastric emptying (Group B). There was no
      difference in symptom score between Group A and Group B. CONCLUSIONS: More than
      half of the patients with CRF on hemodialysis demonstrated normal gastric
      motility, and no or slight GI symptoms. Hemodialytic treatment may improve
      impaired gastric motility and reduce GI symptoms in patients with CRF.

PMID- 18075228
TI  - Alteration of the responses of gastric smooth muscle to endothelin in
      streptozotocin-induced diabetic rats.
AB  - Diabetic gastropathy is suggested to be the result of not only an autonomic
      neuropathy but also to disorder of the spontaneous rhythmic motility of the
      gastric smooth muscle. Attempts were made to investigate the alteration of the
      effects of endothelin-1 (ET-1), which is known to enhance the spontaneous
      activity of gastrointestinal smooth muscle, on gastric activity in streptozotocin
      (STZ)-induced diabetic rats. STZ-induced diabetic rats were prepared by the
      injection of Sprague-Dawley (SD) rats with STZ (i.p.). Isometric mechanical
      responses were recorded in isolated circular smooth muscle strips of the stomach
      antrum, to measure changes in the rhythmicity of the smooth muscle. ET-1 (10 nM)
      significantly elevated the resting tension and the frequency of spontaneous
      contraction, but did not alter the amplitude of the spontaneous oscillatory
      contractions in normal rats. In diabetic rats, ET-1 elevated the resting tension,
      and spontaneous contractions were increased in frequency, however they were
      decreased in amplitude. In normal rats, sarafotoxin S6c (S6c, 10 nM), a selective
      ET(B) receptor agonist, elevated the resting tension slightly and increased both
      the frequency and amplitude of the spontaneous contractions. However, S6c
      significantly elevated the resting tension alone in STZ-induced diabetic rats.
      Selective stimulation of endothelin type A (ET(A)) receptors with ET-1, in the
      presence of a selective antagonist of ET(B) receptors, produced similar responses
      in the gastric muscle of both normal and diabetic rats. These results indicate
      that ET-1 elevates the resting tension and increases the frequency of the
      spontaneous oscillatory contractions in both normal and STZ-induced diabetic
      rats, to a similar extent. However, the specific actions on ET(B) receptors were
      quite different between the two: the elevating actions on the resting tension
      were much greater in STZ-diabetic rats than in normal rats. The results suggested
      the facilitation of ET(B) receptor signaling in the antrum during the
      pathogenesis of diabetic gastropathy.

PMID- 18075229
TI  - Reliability of the time to maximal [13CO2] excretion and the half-[13CO2]
      excretion time as a gastric emptying parameter: assessments using the Wagner
      Nelson method.
AB  - In the [(13)C]-octanoate breath test, two popular parameters have been used to
      quantify gastric emptying rates, namely the time to the maximal [(13)CO(2)]
      excretion (T(max)) and the time to the half-[(13)CO(2)] recovery (T(1/2b)).
      Although each of T(max) and T(1/2b) is closely correlated with the scintigraphic
      half-emptying time, the two parameters occasionally indicate different judgments
      on a gastric emptying rate. In this study, to clarify which of the two parameters
      is more reliable, T(max) and T(1/2b) were compared to the "reference" parameters
      calculated using the Wagner-Nelson method, which allows accurate estimation of a
      time-course of gastric emptying from breath data. Ten healthy male volunteers
      underwent the breath test after ingestion of a muffin meal (320 kcal) containing
      100 mg [(13)C]-octanoate. Breath samples were collected at 15-min intervals for 6
      h. According to the conventional analytical algorithm, T(max) and T(1/2b) were
      mathematically calculated. By applying Wagner-Nelson analysis to the breath test,
      the time-percent gastric retention curve was generated and the half-emptying time
      (T(1/2WN)) was determined. T(1/2WN) was more closely correlated with T(max)
      (r=0.954, P<0.0001) than with T(1/2b) (r=0.782, P=0.008). T(max) was
      significantly correlated with the percent gastric retention value in the early
      (t=0.25 and 0.5 h), the middle (t=1.0 and 1.5 h), and the late (t=2.0 h)
      postprandial phase. T(1/2b) was significantly correlated with the gastric
      retention value in the middle and the late phase, but not with the gastric
      retention value in the early phase. The present results show that T(1/2b) has
      limited capability to reflect gastric emptying in the early postprandial period,
      suggesting that T(max) is more reliable than T(1/2b) as a gastric emptying
      parameter.

PMID- 18075230
TI  - Effect of mental stress on hemoglobin dynamics in trapezius muscles.
AB  - We examined the effect of mental stress on hemoglobin concentrations in the
      trapezius muscles of 20 healthy, non-smoking women. The participants held their
      arms out horizontally (physical stimulus) while standing upright for 1 min with 5
      min intervals of seated rest, or performed Stroop's Color Word Test (mental
      stimulus), or both simultaneously. We measured heart rate, muscle tissue
      hemoglobin (oxy-hemoglobin, OxyHb; deoxy-hemoglobin, DeoHb; total hemoglobin,
      TotHb) concentrations in, and obtained surface electromyograms from the right
      upper trapezius muscle. Changes in the hemoglobin concentration (DeltaOxyHb,
      DeltaDeoHb, DeltaTotHb) induced by physical and/or mental stimuli were
      calculated. Changes with physical stimulus alone were compared with those induced
      by physical plus mental stimuli using repeated measures ANOVA. The DeltaDeoHb
      with physical and mental stimuli was significantly lower (p=0.013) than that with
      the physical stimulus alone, whereas the DeltaOxyHb and the DeltaTotHb values did
      not significantly differ (p=0.281, p=0.230). This finding indicates that mental
      load affects DeltaDeoHb in the trapezius muscle. We think that mental stimulus
      might provoke a reduction in oxygen consumption by the trapezius muscle. Further
      investigations using a longer duration of physical and mental stimuli are
      required.

PMID- 18075231
TI  - Time-dependent changes in serum nitric oxide levels after long bone fracture.
AB  - Nitric oxide (NO) is a free radical of physiological significance. The changes in
      the production of NO during the fracture healing process are not well known. This
      clinical prospective study was planned to determine these changes in patients
      with fractured long bone(s), who underwent surgery in the 3rd week after
      fracture. The patients were divided into two groups: 20 patients with an isolated
      femoral fracture and 20 patients with multiple fractures, including a femoral
      fracture. Venous blood was drawn from the healthy volunteers (n = 20) once, and
      from the patients seven times during 21 days after fracture. NO level was
      measured as nitrite in each serum sample. The serum NO levels at all measurements
      of the patients were significantly higher than those of the control subjects. The
      time-dependent changes in the NO levels were similar in both patient groups. The
      serum NO levels were highest in the first 6 hrs, and then decreased to the lowest
      level on the 3rd day. Subsequently, there was an increasing trend on the 5th, 7th
      and 14th days. At all times of the measurements, the NO levels were higher in
      patients with multiple fractures than in those with the femoral fracture, with
      the significant difference observed at the 6 hrs and on the 7th day. The NO
      levels were decreased on the 21st day after surgery. The present study suggests
      that NO production may be increased in considerable amounts during the first 2
      weeks of fracture healing, particularly in the first 6 hrs.

PMID- 18075232
TI  - Prenatal diagnosis of persistent cloaca associated with VATER (vertebral defects,
      anal atresia, tracheo-esophageal fistula, and renal dysplasia).
AB  - The cloaca is a single canal from which the urinary, genital, and intestinal
      tracts arise around gestational weeks 5-6. Persistent cloaca can result from
      cystic mass formation within the pelvis, which is commonly association with
      multiple developmental defects. VATER association, which is a spectrum of
      anomalies, manifested by vertebral defects, anal atresia, tracheo-esophageal
      fistula with esophageal atresia, and renal dysplasia, arises from abnormalities
      in mesodermal differentiation. Recently, both conditions have been proposed to
      represent a continuous spectrum of anomalies, but the pathophysiology concerning
      the continuity of the development and the clinical condition are still unclear.
      Since renal failure becomes a serious problem after birth, timely infant delivery
      is essential to avoid loss of renal function. We report a patient, in whom the
      overlap between these two conditions was identified, and renal function was lost
      from one kidney. A polycystic mass was found in the fetal abdomen at 26 weeks of
      gestation. By ultrasonography, we detected a polycystic left kidney, a single
      umbilical artery, a ventricular septal defect, an esophageal atresia, ascites, an
      anal atresia, and a cystic mass with debris behind the bladder. The left kidney
      was non-functioning and the right kidney showed signs of hydronephrosis at 30
      weeks of gestation. We measured the size and the blood flow of renal artery
      sequentially, and could deliver the fetus before the function was lost from the
      right kidney. Our observations will help inform future patients where prompt
      intervention can help improve renal function and infant health.

PMID- 18075233
TI  - Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis and Behcet's
      disease.
AB  - Rheumatoid arthritis (RA) is associated with progressive joint destruction and
      disability. Early diagnosis of RA is important, since early and aggressive
      treatments lead to a better outcome. Circulating autoantibodies are a serological
      hallmark of systemic rheumatic diseases. More recently, antibodies directed to a
      cyclic citrullinated peptide, anti-CCP antibodies, have been established as
      specific diagnostic and prognostic tools for RA. The aims of this study were to
      assess the diagnostic and radiological prognostic value of the anti-CCP antibody
      in Turkish patients with RA (n = 97) and those with Behcet's disease (BD) (n =
      46). The study also included 35 healthy controls. Anti-CCP antibodies were
      measured by ELISA, and radiological damage was evaluated by using modified Larsen
      scoring. In the RA group, sensitivity and specificity were 80.4% and 93.5% for
      rheumatoid factor (RF), and 74.2% and 97.8% for anti-CCP antibody, respectively.
      RF was positive in 3 BD patients (6.5%) and in one of the controls (2.9%). In
      contrast, anti-CCP antibodies were detected in one BD patient (2.2%), but not in
      the control subjects. Deformed joint counts and radiographic scores were higher
      in anti-CCP antibody-positive RA patients (n = 72) than those in anti-CCP
      antibody-negative patients (n = 25) (p < 0.05). Moreover, anti-CCP antibody titer
      correlated with deformed joint count (r = 0.224, p < 0.05) and radiographic score
      (r = 0.308, p < 0.05). This study indicates the diagnostic and prognostic utility
      of anti-CCP antibodies in Turkish patients with RA. Importantly, anti-CCP
      antibodies are not associated with BD.

PMID- 18075234
TI  - Procalcitonin as a diagnostic aid in diabetic foot infections.
AB  - The diagnosis of diabetic foot infection (DFI) is usually a challenge to the
      clinician. Procalcitonin (PCT), a 116-amino acid propeptide of calcitonin, is a
      new marker of bacterial infections and sepsis. We evaluated the serum value of
      PCT as a marker of bacterial infection in diabetic patients with foot ulcers.
      Forty-nine diabetic patients with foot ulcers were consecutively enrolled into
      the study. DFI was diagnosed clinically by the presence of purulent secretions or
      at least two of the symptoms of inflammation including redness, warmth, swelling,
      and pain. According to these criteria, DFI was determined in 27 patients (DFI
      group) and not detected in 22 patients (NDFI group). The blood samples were taken
      for biochemical analysis on admission. PCT, white blood cell count (WBC) and
      erythrocyte sedimentation rate (ESR), but not C-reactive protein (CRP), was found
      significantly higher in DFI group compared with NDFI group. The best cut-off
      value, sensitivity and specificity were 0.08 ng/ml, 77% and 100% for PCT, 32.1
      mg/dl, 29% and 100% for CRP, 8.6 10(9)/L, 70% and 72% for WBC and 40.5 mm/h, 77%
      and 77% for ESR, respectively. The area under the receiver operating
      characteristic curve for infection identification was greatest for PCT (0.859; p
      < 0.001), followed by WBC (0.785; p = 0.001), ESR (0.752; p = 0.003), and finally
      CRP (0.625; p = 0.137). These results suggest that PCT may be a useful diagnostic
      marker for DFI. Additional research is needed to better define the role of PCT in
      DFI.

PMID- 18075235
TI  - Exercise improves visual deficits tested by visual evoked potentials in
      streptozotocin-induced diabetic rats.
AB  - Visual evoked potentials (VEP) can be used as an objective non-invasive method to
      study the electrical activity of the visual system. Latency and amplitude
      measurements of VEP demonstrated that diabetes mellitus has been associated with
      increases in the latencies whereas the amplitude measurements revealed
      contradictory results. Although physical exercise has been reported to reduce the
      complications of diabetes mellitus, the effect of exercise on the visual system
      remains unknown. We investigated the effects of long-term moderate physical
      exercise on VEP in streptozotocin (STZ)-diabetic rats. We also measured brain
      thiobarbituric acid-reactive substances (TBARS) to explore the possible
      contribution of lipid peroxidation on the visual system. Animals were divided
      into four groups: control (C), control exercise (CE), diabetic (D) and diabetic
      exercise (DE) groups. Diabetes was induced by a single intraperitoneal injection
      of STZ (60 mg/kg). Three days after the confirmation of diabetes, DE and CE
      groups were trained by running on a motor-driven treadmill with a progressive
      eight-week programme. The animals began running at 10 m/min, 0 degrees slope, 10
      min/day and reached a level of 28 m/min, 6 degrees slope, 60 min/day by week 8.
      TBARS were elevated and VEP latencies were delayed in diabetic rats, indicating
      diabetes-induced defects in the optic pathway. These prolonged latencies were
      restored by exercise training. VEP amplitudes of the DE group were found
      unaltered with the exception of a decrement in P(2)N(2) which represents an early
      component of VEP, suggesting that exercise improves visual system defects in
      diabetic animals at different levels of the optic pathway.

PMID- 18075236
TI  - Soft tissue gas gangrene: a severe complication of emphysematous cholecystitis.
AB  - Soft tissue gas gangrene with myonecrosis is a severe complication of traumatic
      and non-traumatic conditions with a potentially lethal outcome. Emphysematous
      cholecystitis is a complication of acute cholecystitis, which is characterized by
      air accumulation in the gallbladder wall and is reported in the literature as a
      rare causative factor of soft tissue gas gangrene. Here we report 4 patients who
      developed soft tissue gas gangrene as a complication of emphysematous
      cholecystitis. Two patients were female octogenarians (one with a history of
      diabetes mellitus), and underwent percutaneous trans-gallbladder drainage and
      fascia incisions of the affected soft tissue with prompt administration of
      antibiotics. Finally, both of them died. The other two patients were male (32
      years old diabetic and 47 years old with a history of chronic alcoholism). They
      underwent open cholecystectomy. Fascia incisions of the gangrenous areas and
      antibiotic therapy administration were also performed. Both of them were
      discharged from the hospital and are currently in excellent clinical status. We
      also present the ultrasonographic and/or radiologic images of these four
      patients. Soft tissue gas gangrene may complicate emphysematous cholecystitis,
      and clinicians should be aware of the coexistence of these two clinical
      conditions, since immediate management is needed in order to prevent fatal
      outcome.

PMID- 18075237
TI  - Chronological changes of CD4(+) and CD8(+) T cell subsets in the experimental
      autoimmune encephalomyelitis, a mouse model of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory disease of the central nervous system
      (CNS). The etiology of MS remains unclear, but T cells specific for myelin
      components, such as myelin oligodendrocyte glycoprotein (MOG), are thought to
      play a critical role in the onset of MS. Experimental autoimmune
      encephalomyelitis (EAE) has been used as an animal model of MS, and T helper type
      1 (Th1) cells play an essential role for the pathogenesis of EAE through the
      production of Th1 cytokines, interferon-gamma (IFN-gamma) and tumor necrosis
      factor-alpha (TNF-alpha). We examined CD4(+) and CD8(+) T cell responses in the
      spleen and CNS of EAE mice, generated by immunization with a peptide (35-55 amino
      acid residues) of MOG. The number of both CD4(+) and CD8(+) T cells and their MOG
      reactivity in the CNS were associated with increasing disease severity but not
      those in the spleen, suggesting that the MOG-specific CD4(+) and CD8(+) T cells
      in the CNS are involved in the development of EAE. Polymerase chain reaction
      analysis suggested that both CD4(+) and CD8(+) T cells produced IFN-gamma and TNF
      alpha, while CD4(+) T cells also produced interleukin-17 (IL-17), an important
      factor in the development of EAE. Thus, CD4(+) T cells may contribute to the
      induction of EAE by producing IL-17. Furthermore, CD8(+) T cells express higher
      levels of a suppressive cytokine, IL-10. Taking together, our data suggest that
      CD4(+) T cells are involved in the early phase of EAE, whereas CD8(+) T cells
      have a regulatory role in the later stage of EAE.

PMID- 18075238
TI  - Bone marrow-derived cells mobilized by granulocyte-colony stimulating factor
      facilitate vascular regeneration in mouse kidney after ischemia/reperfusion
      injury.
AB  - Bone marrow-derived cells (BMDC) play crucial roles in tissue regeneration.
      Granulocyte-colony stimulating factor (G-CSF) mobilizes BMDC and may facilitate
      the repair of kidney tissues after ischemia/reperfusion (I/R) injury. The tissue
      protective action of resveratrol, an antioxidant, might modify the regenerating
      potential of BMDC in I/R renal injury. This study examined whether G-CSF and/or
      resveratrol affect the recruitment of BMDC into vascular endothelial cells and
      renal tubular cells and the kidney function after I/R injury. I/R renal injury
      was induced in female mice that had been lethally irradiated and transplanted
      with male bone marrow cells. The mice were given saline, resveratrol or G-CSF,
      daily for 7 days. Non-irradiated and non-bone-marrow-transplanted female mice,
      which underwent the same kidney injury, were included as control. White blood
      cell (WBC) count and serum creatinine were monitored. Immunohistologic evaluation
      for renal tubular cells (cytokeratin) and endothelial cells (factor VIII-related
      antigen), and fluorescence in situ hybridization for mouse Y chromosome were
      performed. Although WBC was significantly higher in the G-CSF group, there was no
      significant difference in creatinine levels among all groups. Factor VIII-related
      antigen-positive cells with a Y-chromosome signal were identified in the
      capillary wall between renal tubuli and most frequently seen in the G-CSF group
      (p < 0.0001). Resveratrol did not affect kidney recovery in this model. No
      cytokeratin-positive renal tubular cells having a Y-chromosome signal were
      identified. In conclusion, BMDC are recruited into endothelial cell in I/R renal
      injury without apparent renal tubular cell regeneration, and G-CSF facilitates
      the endothelial cell regeneration.

PMID- 18075239
TI  - Acylcarnitine profiles during carnitine loading and fasting tests in a Japanese
      patient with medium-chain acyl-CoA dehydrogenase deficiency.
AB  - Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is rare among Asian
      individuals, and the clinical course and biochemical findings remain unclear. We
      report herein a 3-year-old Japanese girl with MCADD. The diagnosis was suggested
      by acylcarnitine profiles and confirmed by enzyme activity and genetic analysis
      after clinical presentation. Our described method with high-performance liquid
      chromatography/tandem mass spectrometry allows quantification of levels of n
      octanoylcarnitine (C8-N) and other isomers (e.g. valproylcarnitine). We examined
      the patient's acylcarnitine profiles in serum and urine samples during carnitine
      loading and 14-hr fasting tests with/without carnitine supplementation. Under
      hypocarnitinemia, serum level of C8-N was 0.16 micromol/l and C8
      N/decanoylcarnitine (C10) ratio was 1.8, which did not correspond to the
      diagnostic criteria for MCADD. However, intravenous carnitine loading test (100
      mg/kg/day for 3 days and 50 mg/kg/day for 1 day) led to increased serum C8-N
      levels and urinary excretion was obvious, strongly suggesting MCADD. In the
      fasting test with carnitine supplementation, marked production of acylcarnitines
      (C8-N > C2 >> C6 > C10) was found, compared to the fasting test without carnitine
      supplementation. These results indicate that carnitine supplementation may be
      useful for detoxification of accumulated acylcarnitines even in an asymptomatic
      state. Moreover, the one-point examination for serum C8-N level and/or C8-N/C10
      ratio may make the diagnosis of MCADD difficult, particularly in the presence of
      significant hypocarnitinemia. To avoid this pitfall, attention should be given to
      serum levels of free carnitine, and carnitine loading may be demanded in
      hypocarnitinemia.

PMID- 18075240
TI  - Elevated serum C-reactive protein levels as a predictive indicator for subsequent
      renal impairment in patients with acute heart failure.
AB  - Renal impairment is often observed in acute heart failure (HF), which is an
      independent prognostic factor. It is important to identify high-risk patients,
      who need close follow-up and intensive care for renal protection. This study was
      conducted to identify the factors associated with the subsequent occurrence of HF
      related renal dysfunction in patients, who were admitted to the hospitals due to
      acute HF symptoms. We evaluated 254 consecutive patients with acute HF. HF
      related renal dysfunction was defined when highest serum creatinine level was
      greater than 1.2 mg/dl and the serum creatinine level increased by more than 50%
      compared with the baseline value during the admission. Forty patients with acute
      HF (16%) had subsequent renal dysfunction after admission. Elevated serum C
      reactive protein (CRP) levels (> or = 5 mg/dl, odds ratio 2.51, p = 0.008 by
      univariate analysis, odds ratio 2.43, p = 0.019 by multivariate analysis) during
      the first week after admission and over-reduction of body weight (> or = 4.5 kg,
      odds ratio 2.68, p = 0.005 by univariate analysis, odds ratio 2.53, p = 0.010 by
      multivariate analysis) by acute HF treatment were significantly associated with
      this phenomenon. Patients with high CRP levels (> or = 5 mg/dl) during the first
      week after admission showed a significantly greater elevation of serum creatinine
      levels as compared to the levels before admission than those with low CRP levels
      (< 5 mg/dl). In conclsion, higher serum levels of CRP could predict the
      subsequent renal impairment in patients admitted with the worsening of HF
      symptoms.

PMID- 18075241
TI  - Mood change tendency and fasting plasma glucose levels in a Japanese female
      population.
AB  - Internal stress can modify values in blood examinations such as glucose. Mood
      change releases us from the stress state, and the mood change tendency (MCT) may
      show individual differences. However, little is known about whether individual
      mood change tendencies in daily life affect fasting plasma glucose (FPG) levels.
      We investigated the effects of clinical characteristics including age, body mass
      index (BMI), smoking, alcohol habits and self-reported MCT (an answer to the
      inquiry on their daily MCT: good, average, or poor) on FPG values among 272
      Japanese females (mean age 48.4 +/- 9.3 years). Subjects with normal to impaired
      fasting glucose levels (less than 7.0 mmol/L) were included in this study. The
      mean FPG levels in subjects with good, average and poor MCT were 5.32 +/- 0.48,
      5.36 +/- 0.50 and 5.58 +/- 0.69 mmol/L, respectively. A significant difference
      was noted between subjects with good and poor MCT (p = 0.02). There was no
      significant difference in BMI levels among MCT-based groups. Pearson's rank
      correlation and multiple regression analysis, using FPG levels and other
      variables, demonstrated a significant relationship between FPG levels and MCT (p
      < or =0.01), along with age and BMI. These results suggest slight but significant
      effects of individual MCT on FPG, and that a consideration of MCT may
      occasionally be needed in the interpretation and management of FPG levels in the
      Japanese female population.

PMID- 18075242
TI  - The cerebrospinal fluid level of 5-methylterahydrofolate in a Japanese boy with
      hypomyelination with atrophy of the basal ganglia and cerebellum.

PMID- 18075243
TI  - Diagnostic and prognostic utility of t(14;18) in follicular lymphoma.
AB  - BACKGROUND: Follicular lymphoma (FL) is one of the most common non-Hodgkin's
      lymphomas of B cells, being closely associated with a t(14;18) translocation.
      Detection of t(14;18), which is present in 70-95% of FL, might aid in FL
      diagnosis. OBJECTIVE: To compare the efficacy of routine polymerase chain
      reaction (PCR) and fluorescence in situ hybridization (FISH) techniques in
      detecting t(14;18) in paraffin-embedded tissue samples of FL patients at
      different stages. Combined with other immunophenotypic biological determinants,
      detection of t(14;18) might help to determine patients at increased risk
      according to the FL International Prognostic Index (FLIPI) and therefore
      facilitate appropriate treatment. DESIGN AND METHODS: This study was mainly based
      on a retrospective examination of formalin-fixed, paraffin-embedded lymph nodes.
      We selected fixed tissue samples of 21 FL patients treated at the National Cancer
      Institute Center in the period from 2000 to 2001. RESULTS: FISH techniques could
      detect 14 of 18 FL cases with a sensitivity of 77.8%, while the PCR technique
      could detect only 11 of 18 FL cases with a sensitivity of 61.1%, resulting in a
      statistically significant difference between both techniques (p = 0.004).
      According to the FLIPI index, 9 of the 18 FL patients were categorized into the
      high-risk group (50%), 5 in the intermediated-risk group (27.8%) and 4 in the low
      risk group (22.2%). CONCLUSION: The sensitivity of FISH is superior to that of
      PCR in the detection of the t(14;18) translocation in paraffin-embedded tissue
      samples. There is a statistically significant correlation between both CD10 and
      FISH with FLIPI.

PMID- 18075244
TI  - Myofascial trigger point:a possible way of modulating tinnitus.
AB  - In order to investigate whether myofascial trigger points can modulate tinnitus,
      as well as the association between tinnitus and myofascial trigger points, 94
      individuals with and 94 without tinnitus, matched by age and gender, were
      analyzed by means of bilateral digital pressure of 9 muscles. Temporary
      modulation of tinnitus was frequently observed (55.9%) during digital pressure,
      mainly in the masseter. The rate of tinnitus modulation was significantly higher
      on the same side of the myofascial trigger point subject to examination in 6 out
      of 9 muscles. An association between tinnitus and the presence of myofascial
      trigger points was observed (p < 0.001), as well as a laterality association
      between the ear with the worst tinnitus and the side of the body with more
      myofascial trigger points (p < 0.001). Thus, this relationship could be explained
      not only by somatosensory-auditory system interactions but also by the influence
      of the sympathetic system.

PMID- 18075245
TI  - Electrically evoked auditory steady-state responses in a guinea pig model:
      latency estimates and effects of stimulus parameters.
AB  - Cochlear implant speech processors typically extract envelope information of
      speech signals for presentation to the auditory nerve as modulated trains of
      electric pulses. Recent studies showed the feasibility of recording, at the
      scalp, the electrically evoked auditory steady-state response using amplitude
      modulated electric stimuli. Sinusoidally amplitude-modulated electric stimuli
      were used to elicit such responses from guinea pigs in order to characterize this
      response. Response latencies were derived to provide insight regarding neural
      generator sites. Two distinct sites, one cortical and another more peripheral,
      were indicated by latency estimates of 22 and 2 ms, respectively, with the former
      evoked by lower (13-49 Hz) and the latter by higher (55-320 Hz) modulation
      frequencies. Furthermore, response amplitudes declined with increasing carrier
      frequency, exhibited a compressive growth with increasing modulation depths, and
      were sensitive to modulation depths to as low as 5%.

PMID- 18075246
TI  - Prospective mutation screening of three common deafness genes in a large
      Taiwanese Cohort with idiopathic bilateral sensorineural hearing impairment
      reveals a difference in the results between families from hospitals and those
      from rehabilitation facilities.
AB  - Accurate epidemiological data on common deafness genes are essential to improve
      the efficiency and to reduce the cost of molecular diagnosis. They may depend on
      several factors, including a clear delineation of the source of patients being
      studied. In the present study, we hypothesize that patients with idiopathic
      sensorineural hearing loss recruited from different sources might reveal
      discrepancies in the epidemiological results of genetic screening, because
      patients from different sources might demonstrate distinct clinical or audiologic
      features and thus result in biased selection of subjects. To elucidate the
      relative importance of common deafness genes in Taiwanese and to verify our
      hypothesis, we conducted a prospective project screening mutations in GJB2,
      SLC26A4 and mitochondrial 12S rRNA gene in a total of 420 Taiwanese families with
      idiopathic bilateral sensorineural hearing loss, of which 325 families were
      recruited from hospitals and 95 from hearing rehabilitation facilities. Allele
      frequencies of common mutations in these three genes and distributions of the
      corresponding genotypes were then compared between the two groups. The allele
      frequencies of mutations in SLC26A4, GJB2 and mitochondrial 12S rRNA in the
      probands of the 420 families were 14.4, 21.7 and 3.8%, respectively. The allele
      frequency of SLC26A4 mutations in the hospital group was significantly higher
      than that in the rehabilitation facility group (16.2 vs. 8.4%, chi(2)-test, p <
      0.05), whereas no difference in the frequencies of GJB2 mutations and
      mitochondrial 12S rRNA mutations was found between the two groups. Distributions
      of probands classified by SLC26A4 genotypes were also different between the two
      groups (chi(2)-test, p < 0.05). Accordingly, a discrepancy in the genetic
      screening results might exist between different sources of idiopathic hearing
      impaired patients. Further analysis of audiological results and construction of a
      logistic regression model showed that different audiological features, namely
      hearing levels and hearing loss patterns, might be responsible for the unequal
      distributions of mutations and probands between the hospital and rehabilitation
      facility groups.

PMID- 18075247
TI  - Oxidized low-density lipoprotein biomarkers in patients with end-stage renal
      failure: acute effects of hemodialysis.
AB  - OBJECTIVE: To assess the effect of end-stage renal failure on oxidized low
      density lipoprotein (OxLDL) biomarkers and the acute effects of hemodialysis.
      Oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles
      (OxPL/apoB) have been associated with cardiovascular disease and new
      cardiovascular events. Patients with end-stage renal failure have increased
      oxidative stress and are at significantly increased risk of cardiovascular
      disease. METHODS AND RESULTS: Fifty-two stable patients with end-stage renal
      failure undergoing chronic hemodialysis were included in the study. Pre and post
      hemodialysis blood samples were obtained for measurement of OxLDL biomarkers:
      oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles
      (OxPL/apoB) measured by antibody E06, IgG and IgM autoantibody titers to copper
      oxidized LDL (Cu-OxLDL) and malondialdehyde (MDA)-LDL, IgG and IgM apolipoprotein
      B-100-immune complexes (IC/apoB). Traditional laboratory variables as well as C
      reactive protein (CRP) and lipoprotein(a) [Lp(a)] were also measured. For the
      baseline variables, the distribution of OxPL/apoB and Lp(a) were skewed to lower
      values, and a strong correlation was noted between OxPL/apoB and Lp(a) (r = 0.94,
      p < 0.0001). No major associations were noted between OxLDL biomarkers and age,
      gender or dialytic age. There were also no correlations between OxLDL biomarkers
      and traditional risk factors, CRP, body mass index, serum creatinine,
      hypertension or intravenous iron therapy. Following dialysis, there as a
      significant reduction in OxPL/apoB (-7.5%, p = 0.048) and triglyceride levels (
      10.8%, p = 0.005). All other OxLDL biomarkers, CRP, total cholesterol, LDL-C, HDL
      C and apoB-100 increased significantly (range 6.3-26.9%, p value range 0.005 to
      <0.0001). Total protein plasma levels increased 8.8% (p = 0.014 compared to
      predialysis) following dialysis, consistent with a hemoconcentration effect of
      hemodialysis. CONCLUSION: In end-stage renal failure patients undergoing
      hemodialysis, a reduction in OxPL/apoB levels was noted, despite the
      hemoconcentrating and strong pro-oxidant milieu of hemodialysis. Studies in
      larger populations of end-stage renal failure patients are needed to assess
      whether these findings predict future clinical outcomes.

PMID- 18075248
TI  - Effect of climatic temperature on fluid gain in hemodialysis patients with
      different degrees of overhydration.
AB  - BACKGROUND: To assess the effect of seasonal temperature on the interdialytic
      body weight gain (deltaBW), %deltaBW/dry weight (DW), and pre-dialysis blood
      pressure in chronic hemodialysis (HD) patients with different degrees of
      overhydration. METHOD: Year 2005 was divided into two seasons: 'cold' (the
      coolest 5 months) and 'hot' (the hottest 5 months). A total of 221 end-stage
      renal disease patients treated with HD at our center throughout the year 2005
      were enrolled. RESULTS: DeltaBW showed a reversed trend to the water evaporation
      rate, which paralleled temperature change. Increases of deltaBW and %deltaBW/DW
      in cold weather were more significant in non-diabetes mellitus than diabetes
      mellitus. Only patients in the bottom two quartiles for %deltaBW/DW in hot
      weather (i.e., <5%) showed a cold weather-induced increase in %deltaBW/DW.
      CONCLUSION: A cold weather-induced increase in fluid accumulation occurs in only
      those patients with less hypervolemia during the hot season.

PMID- 18075249
TI  - Perseveration in Alzheimer's disease.
AB  - BACKGROUND/AIMS AND METHODS: Perseveration is common in Alzheimer's disease (AD).
      We document the type and quantitative burden of perseveration as cognitive
      decline progresses from normal aging (n = 30) through mild AD (n = 20) to
      moderate AD (n = 20) by administering a semantic verbal fluency task. RESULTS: We
      found perseveration to increase significantly with increasing severity of AD and
      different types of perseveration that distinguish the subject groups in a
      statistically significant manner. Recurrent and continuous perseverations appear
      early in AD. As the disease progresses in severity into moderate stage, the
      number of recurrent and continuous perseverations increases, and stuck-in-set
      perseverations emerge. CONCLUSION: The different types of perseveration are
      likely to reflect the progressive deterioration of different brain regions in AD.

PMID- 18075250
TI  - Cerebellar granule cell migration and the effects of alcohol.
AB  - In the developing brain the majority of neurons migrate from their birthplace to
      their final destination. This active movement is essential for the formation of
      cortical layers and nuclei. The impairment of migration does not affect the
      viability of neurons but often results in abnormal differentiation. The proper
      migration of neurons requires the orchestrated activities of multiple cellular
      and molecular events, such as pathway selection, the activation of specific
      receptors and channels, and the assembly and disassembly of cytoskeletal
      components. The migration of neurons is very vulnerable to exposure to
      environmental toxins, such as alcohol. In this article, we will focus on recent
      developments in the migration of cerebellar granule cells. First, we will
      describe when, where and how granule cells migrate through different cortical
      layers to reach their final destination. Second, we will present how internal
      programs control the sequential changes in granule cell migration. Third, we will
      review the roles of external guidance cues and transmembrane signals in granule
      cell migration. Finally, we will reveal mechanisms by which alcohol exposure
      impairs granule cell migration.

PMID- 18075251
TI  - Role of intermediate progenitor cells in cerebral cortex development.
AB  - Intermediate progenitor cells (IPCs) are a type of neurogenic transient
      amplifying cells in the developing cerebral cortex. IPCs divide symmetrically at
      basal (abventricular) positions in the neuroepithelium to produce pairs of new
      neurons or, in amplifying divisions, pairs of new IPCs. In contrast, radial unit
      progenitors (neuroepithelial cells and radial glia) divide at the apical
      (ventricular) surface and produce only single neurons or single IPCs by
      asymmetric division, or self-amplify by symmetric division. Histologically, IPCs
      are most prominent during the middle and late stages of neurogenesis, when they
      accumulate in the subventricular zone, a progenitor compartment linked to the
      genesis of upper neocortical layers (II-IV). Nevertheless, IPCs are present
      throughout cortical neurogenesis and produce neurons for all layers. In mice,
      changes in the abundance of IPCs caused by mutations of Pax6, Ngn2, Id4 and other
      genes are associated with parallel changes in cortical thickness but not surface
      area. In gyrencephalic brains, IPCs may play broader roles in determining not
      only laminar thickness, but also cortical surface area and gyral patterns. We
      propose that regulation of IPC genesis and amplification across developmental
      stages and regional subdivisions modulates laminar neurogenesis and contributes
      to the cytoarchitectonic differentiation of cortical areas.

PMID- 18075252
TI  - Migration of neuroblasts from neurogenic placodes.
AB  - Peripheral neurons involved in cephalic sensory systems are born in the ectoderm
      at a distance from the neural tube. The neuroblasts migrate internally, coalesce
      to form ganglia and extend axons to the central nervous system. This process has
      long been evident but little is known about the way it occurs. We have shown that
      coordination of the migration and integration with the hindbrain occurs through
      interaction with neural crest cells.

PMID- 18075253
TI  - Molecular pathways regulating cytoskeletal organization and morphological changes
      in migrating neurons.
AB  - Neuronal migration is a pivotal step for architectural and functional brain
      development. Migrating neurons exhibit various morphological changes, based on
      cytoskeletal organization. In addition to many genetic studies revealing the
      involvement of several cytoskeletal and signaling molecules in cortical neuronal
      migration (e.g. doublecortin, Lis1, Filamin A, cyclin-dependent kinase 5, Reelin
      and Dab1), cell biological studies and recently developed techniques, including
      in utero electroporation, have uncovered detailed functions of these molecules as
      well as novel molecules, such as Rho family GTPases, focal adhesion kinase, c-jun
      N-terminal kinase and p27(kip1). In this review, we introduce the molecular
      pathways underlying cortical neuronal migration and morphological changes, with
      particular focus on recent findings for the regulatory mechanisms of actin
      cytoskeleton and microtubules.

PMID- 18075254
TI  - Functions of Rac GTPases during neuronal development.
AB  - The small GTPases of the Rho family are important regulators of the actin
      cytoskeleton and are critical for several aspects of neuronal development
      including the establishment of neuronal polarity, extension of axon and
      dendrites, neurite branching, axonal navigation and synapse formation. The aim of
      this review is to present evidence supporting the function of Rac and Rac-related
      proteins in different aspects of neuronal maturation, based on work performed
      with organisms including nematodes, Drosophila, Xenopus and mice, and with
      primary cultures of developing neurons. Three of the 4 vertebrate Rac-related
      genes, namely Rac1, Rac3 and RhoG, are expressed in the nervous system, and
      several data support an essential role of all 3 GTPases in distinct aspects of
      neuronal development and function. Two important points emerge from the analysis
      presented: highly homologous Rac-related proteins may perform different functions
      in the developing nervous system; on the other hand, the data also indicate that
      similar GTPases may perform redundant functions in vivo.

PMID- 18075255
TI  - Function of PTEN during the formation and maintenance of neuronal circuits in the
      brain.
AB  - PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor
      suppressor that can inhibit proliferation and migration and controls apoptosis in
      a number of cell types, mainly through inhibition of the phosphoinositide 3
      kinase (PI3K) signaling pathway. Patients carrying inactivating mutations of PTEN
      show a prevalence to develop tumors that can coincide with neurological defects
      such as mental retardation, ataxia and seizures. A number of in vitro and in vivo
      studies were instrumental in uncovering a direct correlation between deregulated
      PI3K/PTEN signaling and changes in neuronal morphogenesis, which is likely to
      have profound bearings upon the pathogenesis of neurological symptoms. This
      review outlines recent work on the function of PTEN during vertebrate brain
      development and the current understanding of the signaling pathways downstream of
      PTEN that control neuronal connectivity in the brain.

PMID- 18075256
TI  - How neuronal migration contributes to the morphogenesis of the CNS: insights from
      the zebrafish.
AB  - We used transgenic zebrafish expressing GFP or YFP in subpopulations of neurons
      to study the migration, homing process and axon extension of groups of CNS
      neurons in different regions of the zebrafish brain. We found that extensive
      migration takes place at all levels of the CNS and gives rise to nuclei or cell
      populations with specific identities. Here, we describe 4 previously unknown or
      only partially characterized migratory events taking place in the zebrafish
      telencephalon and rhombic lip, using 3 different transgenic lines, and identify
      the phenotypes of the cells undertaking these migrations. The migration of a
      subgroup of mitral cell precursors from the dorsocaudal telencephalon to the
      olfactory bulb, visualized in the tg(tbr1:YFP) transgenic line, is coupled with
      morphogenetic transformation of the dorsal telencephalon. The tg(1.4dlx5a-6a:GFP)
      transgenic line provides a means to analyze the migration of GABAergic
      interneurons from the ventral to the dorsal telencephalon, thus extending the
      occurrence of this migration to another vertebrate. The tg(Xeom:GFP) transgenic
      line provides the first demonstration of the dorsoventral migration of
      glutamatergic septal neurons, present in mammals and now described in fish, thus
      reconciling the contrasting evidence of dorsal patterning genes (tbr1, eomes)
      expressed in a ventral cell population. Furthermore, migration studies in the
      tg(1.4dlx5a-6a:GFP) and tg(Xeom:GFP) lines help determine the origin of 2
      important cell populations in the fish cerebellum: projection neurons and
      Purkinje cells. These examples reinforce the concept that migratory events
      contribute to the distribution of cell types with diverse identities through the
      CNS and that zebrafish transgenic lines represent excellent tools to study these
      events.

PMID- 18075258
TI  - The potential role of cyclin-dependent kinase 5 in focal cortical dysplasia.
AB  - Focal cortical dysplasia (FCD) is the most common malformation of cortical
      development found in epilepsy surgical series. Characterised by cortical
      mislamination, dysplastic neurons and, in a subgroup of cases, balloon cells, FCD
      is potently epileptogenic. Despite decades of study, the underlying aetiology of
      FCD remains uncertain and research has been hampered by the lack of a good animal
      model in which to simulate the condition. In this article we review some of the
      potential molecular mechanisms that might underpin human FCD. In particular we
      examine the potential role of cyclin-dependent kinase 5 and its principal
      activator p35 in FCD and estimate the contribution that deregulation of cyclin
      dependent kinase 5 might make to the pathogenesis of this condition.

PMID- 18075257
TI  - Histogenetic processes leading to the laminated neocortex: migration is only a
      part of the story.
AB  - The principal events of neocortical histogenesis were anticipated by work
      published prior to the 20th century. These were neuronal proliferation and
      migration and the complex events of cortical pattern formation leading to a
      laminated architecture where each layer is dominated by a principal neuronal
      class. Work that has followed has extended the knowledge of the workings of the
      proliferative epithelium, cellular mechanisms of migration and events through
      which cells are winnowed and then differentiate once their postmigratory
      positions are established. Work yet ahead will emphasize mechanisms that
      coordinate the molecular events that integrate proliferation and cell class
      specification in relation to the final neocortical neural system map.

PMID- 18075259
TI  - Migratory behavior of presumptive interneurons is affected by AMPA receptor
      activation in slice cultures of embryonic mouse neocortex.
AB  - It has been reported that functional alpha-amino-3-hydroxy-5-methyl-isoxazolpro
      prionic acid (AMPA) receptors permeable to calcium are already expressed by
      tangentially migrating prospective interneurons in the developing rodent cerebral
      cortex. However, the role of these receptors is not yet fully understood. To
      examine the effect of activation of AMPA receptors on tangential migration, we
      exposed migrating prospective interneurons derived from the medial ganglionic
      eminence (MGE) to AMPA in slice cultures and performed time lapse imaging. In the
      neocortex, a subpopulation of MGE-derived cells stopped migration or changed the
      direction of migration in response to AMPA in a dose-dependent manner. In
      contrast, neither MGE-derived cells migrating in the subcortical territory nor
      radially migrating cells in the neocortex were affected by exposure to AMPA.
      Transfection of dominant-negative AMPA receptor subunit GluR1 to the tangentially
      migrating cells prevented the effects of AMPA on migration. This study provides
      evidence that the activation of AMPA receptors can directly affect tangential
      migration in the neocortical part of telencephalic slice cultures.

PMID- 18075260
TI  - Stromal-derived factor 1 signalling regulates radial and tangential migration in
      the developing cerebral cortex.
AB  - Stromal-derived factor 1 (SDF-1), a known chemoattractant, and its receptor CXCR4
      are widely expressed in the developing and adult cerebral cortex. Recent studies
      have highlighted potential roles for SDF-1 during early cortical development. In
      view of the current findings, our histological analysis has revealed a distinct
      pattern of SDF-1 expression in the developing cerebral cortex at a time when cell
      proliferation and migration are at peak. To determine the role of chemokine
      signalling during early cortical development, embryonic rat brain slices were
      exposed to a medium containing secreted SDF-1 to perturb the endogenous levels of
      chemokine. Alternatively, brain slices were treated with 40 muM of T140 or
      AMD3100, known antagonists of CXCR4. Using these experimental approaches, we
      demonstrate that chemokine signalling is imperative for the maintenance of the
      early cortical plate. In addition, we provide evidence that both neurogenesis and
      radial migration are concomitantly regulated by this signalling system.
      Conversely, interneurons, although not dependent on SDF-1 signalling to
      transgress the telencephalic boundary, require the chemokine to maintain their
      tangential migration. Collectively, our results demonstrate that SDF-1 with its
      distinct pattern of expression is essential and uniquely positioned to regulate
      key developmental events that underlie the formation of the cerebral cortex.

PMID- 18075261
TI  - Nocodazole-induced changes in microtubule dynamics impair the morphology and
      directionality of migrating medial ganglionic eminence cells.
AB  - We have shown previously that actomyosin contractility plays an important role in
      controlling nuclear movements in future interneurons born in the medial
      ganglionic eminence (MGE) [Bellion et al.: J Neurosci 2005;25:5691-5699]. Because
      microtubules are known to control the structural and motile properties of
      migrating neurons, we asked whether alterations in the dynamic instability of
      microtubules would impair MGE cell migration. Migration was analyzed in flat
      cocultures in which green-fluorescent-protein-expressing MGE cells migrate on
      cortical cells from their explant of origin. A low (100 nM) concentration of
      nocodazole shortened the leading process of MGE cells that nevertheless continued
      to migrate at the same rate but frequently changed their direction of migration
      relative to control cells. MGE cells treated with a higher (1 muM) concentration
      of nocodazole that strongly destabilized microtubules took on multipolar
      morphology. They extended thin and labile processes. MGE cells no longer
      exhibited directional migration and migration velocity slowed 2-fold. These
      results suggest that microtubule stability is crucial for maintaining polarity
      and controlling the directional migration of MGE cells, whereas additional
      mechanisms are required to control cell motility.

PMID- 18075262
TI  - The role of DCX and LIS1 in migration through the lateral cortical stream of
      developing forebrain.
AB  - During forebrain development the lateral cortical stream (LCS) supplies neurons
      to structures in the ventral telencephalon including the amygdala and piriform
      cortex. In the current study, we used spatially directed in utero electroporation
      and RNAi to investigate mechanisms of migration to the ventral telencephalon.
      Cells labeled by in utero electroporation of the lateral ventricular zone
      migrated into the LCS, and entered the lateral neocortex, piriform cortex and
      amygdala, where they differentiated primarily as pyramidal neurons. RNAi of DCX
      or LIS1 disrupted migration into amygdala and piriform cortex and caused many
      neurons to accumulate in the external and amygdalar capsules. RNAi of LIS1 and
      DCX had similar as well as distinguishable effects on the pattern of altered
      migration. Combinatorial RNAi of LIS1 and DCX further suggested interaction in
      the functions of LIS1 and DCX on the morphology and migration of migrating
      neurons in the LCS. Together, these results confirm that the LCS contributes
      pyramidal neurons to ventral forebrain structures and reveals that DCX and LIS1
      have important functions in this major migratory pathway in the developing
      forebrain.

PMID- 18075264
TI  - Alternative transcripts of Dclk1 and Dclk2 and their expression in doublecortin
      knockout mice.
AB  - The doublecortin (DCX) gene, mutated in X-linked human lissencephaly, has 2 close
      paralogs, doublecortin-like kinase 1 and 2 (Dclk1 and 2). In this study we
      attempted to better understand the dramatic differences between human and mouse
      DCX/Dcx-deficient phenotypes, focusing on the Dclk genes which are likely to
      compensate for Dcx function in the mouse. Using sequence database screens,
      Northern blot analyses and in situ hybridization experiments, we characterized
      the developmental transcripts of Dclk1 and 2, questioning their conservation
      between mouse and human, and their similarity to Dcx. Like Dcx, Dcx-like
      transcripts of the Dclk1 gene are expressed in postmitotic neurons in the
      developing cortex. No changes of expression were observed at the RNA level for
      these transcripts in Dcx knockout mice. However, a minor change in expression at
      the protein level was detected. The Dclk2 gene is less well characterized than
      Dclk1 and we show here that it is expressed both in proliferating cells and
      postmitotic neurons, with a notably strong expression in the ventral
      telencephalon. No major differences in Dclk2 expression at the RNA and protein
      levels were identified comparing Dcx knockout and wild-type brains. We also
      analyzed Dclk1 and 2 expression in the hippocampal CA3 region which, unlike the
      neocortex, is abnormal in Dcx knockout mice. Interestingly, each transcript was
      expressed in CA3 neurons, including in the heterotopic pyramidal layer of Dcx
      knockout animals, but is presumably not able to compensate for a lack of Dcx.
      These results, in addition to characterizing the transcript diversity of an
      important family of genes, should facilitate further studies of compensation in
      Dcx-deficient mice.

PMID- 18075263
TI  - Genetic enhancement of the Lis1+/- phenotype by a heterozygous mutation in the
      adenomatous polyposis coli gene.
AB  - Hemizygous Lis1 mutations cause type 1 lissencephaly, a neuronal migration
      disorder in humans. The Lis1+/- mouse is a model for lissencephaly; mice exhibit
      neuronal migration defects but are viable and fertile. On an inbred genetic
      background, 20% of Lis1+/- mice develop hydrocephalus and die prematurely. Lis1
      functions with the microtubule motor cytoplasmic dynein. Because dynactin, a
      dynein regulator, interacts with end-binding protein 1 (EB1) and beta-catenin,
      two known binding partners of the adenomatous polyposis coli (APC) protein, we
      looked for a genetic interaction between Lis1 and APC. Mice with a heterozygous
      truncating mutation in APC (Min mutation) do not exhibit neuronal migration
      defects or develop hydrocephalus. However, the presence of the APC mutation
      increases the migration deficit and the incidence of hydrocephalus in Lis1+/-
      animals. Lis1 and dynein distribution is altered in cells derived from Min mice,
      and both Lis1 and dynein interact with the C terminus of APC in vitro. Together,
      our findings point to a previously unknown interaction between APC and Lis1
      during mammalian brain development.

PMID- 18075265
TI  - Doublecortin supports the development of dendritic arbors in primary hippocampal
      neurons.
AB  - Doublecortin (DCX) is a microtubule-associated protein necessary for neuronal
      migration. In spite of its ubiquitous distribution in dendrites, its possible
      role in dendrite development has not yet been documented. The present study
      examined the effects of different expression levels of DCX on the arborization of
      dendrites in cultured hippocampal neurons. Reduced expression of DCX following
      RNAi transfection resulted in reduced branch points, total length and complexity
      of the dendrites. Overexpression of DCX resulted in an increase in branch points
      and complexity of the dendrites. In contrast to control green fluorescent protein
      cells, DCX-overexpressing cells maintained highly branched and complex dendritic
      trees when subjected to reduced neuronal activity by blockade of immature GABA(A)
      receptors. These results suggest that DCX supports developing dendrites, in
      addition to its role in neuronal migration.

PMID- 18075266
TI  - Microtubule-associated protein 1B interaction with tubulin tyrosine ligase
      contributes to the control of microtubule tyrosination.
AB  - Microtubule-associated protein 1B (MAP1B) is the first microtubule-associated
      protein to be expressed during nervous system development. MAP1B belongs to a
      large family of proteins that contribute to the stabilization and/or enhancement
      of microtubule polymerization. These functions are related to the control of the
      dynamic properties of microtubules. The C-terminal domain of the neuronal alpha
      tubulin isotype is characterized by the presence of an acidic polypeptide, with
      the last amino acid being tyrosine. This tyrosine residue may be enzymatically
      removed from the protein by an unknown carboxypeptidase activity. Subsequently,
      the tyrosine residue is again incorporated into this tubulin by another enzyme,
      tubulin tyrosine ligase, to yield tyrosinated tubulin. Because neurons lacking
      MAP1B have a reduced proportion of tyrosinated microtubules, we analyzed the
      possible interaction between MAP1B and tubulin tyrosine ligase. Our results show
      that these proteins indeed interact and that the interaction is not affected by
      MAP1B phosphorylation. Additionally, neurons lacking MAP1B, when exposed to drugs
      that reversibly depolymerize microtubules, do not fully recover tyrosinated
      microtubules upon drug removal. These results suggest that MAP1B regulates
      tyrosination of alpha-tubulin in neuronal microtubules. This regulation may be
      important for general processes involved in nervous system development such as
      axonal guidance and neuronal migration.

PMID- 18075267
TI  - Exploring cortical subplate evolution using magnetic resonance imaging of the
      fetal brain.
AB  - The subplate is a transient structure essential for normal development of the
      cortex. We used magnetic resonance imaging of the fetal brain to assess cortical
      subplate evolution between 20 and 35 weeks gestation. Two-dimensional measures of
      diameter were obtained for the cortex, subplate and fetal white matter. The
      subplate was originally seen as a continuous band at early gestations measuring
      up to 4.5 mm. It became magnetic resonance invisible from approximately 28 weeks
      initially from the depths of the sulci and then from the tops of the gyri. The
      disappearance of the subplate was regional, involuting most rapidly in the
      parietal lobe and remaining prominent in the anterior temporal lobe up to 35
      weeks. x

PMID- 18075268
TI  - Therapeutic antibodies in multiple sclerosis.

PMID- 18075269
TI  - Intravenous polyclonal human immunoglobulins in multiple sclerosis.
AB  - Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating
      diseases of the peripheral nervous system. IVIG exerts a number of effects that
      may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have
      been performed in relapsing-remitting MS. A meta-analysis of the four trials has
      shown that IVIG reduces the relapse rate and, possibly, disease progression. In
      patients with a first episode of demyelinating disease, IVIG delays the time to
      the second relapse and thereby to the diagnosis of definite MS. In patients with
      an acute MS relapse, IVIG as add-on therapy to methylprednisolone does not make
      remission of symptoms faster or more complete. IVIG does not seem to be of any
      benefit to chronic visual or motor symptoms in MS. In secondary progressive MS,
      IVIG has not shown any effect on disease progression, relapses or new magnetic
      resonance imaging lesions. Experimental studies in the MS model experimental
      autoimmune encephalomyelitis in rats demonstrate that IVIG has to be administered
      at the time of induction of a relapse in order to be effective. In conclusion,
      IVIG can be considered as a second-line treatment to approved therapies for
      relapsing-remitting MS, but the ideal dosage of IVIG still needs to be
      determined. In order to be a first-line treatment for MS, the beneficial effect
      should be confirmed in a large-scale placebo-controlled survey, or in a study
      comparing the effect with approved therapies for relapsing-remitting MS using
      appropriate clinical and magnetic resonance imaging outcome measures.

PMID- 18075271
TI  - Humanized anti-CD25 antibody treatment with daclizumab in multiple sclerosis.
AB  - Monoclonal antibodies against a variety of receptors and molecules are currently
      being introduced in clinical medicine. One of these targets is the interleukin-2
      receptor alpha-chain CD25. The humanized monoclonal anti-CD25 antibody daclizumab
      (Zenapax) has been approved several years ago for the prevention of
      allotransplant rejection and adult T cell leukemia. Following promising
      observations in uveitis, daclizumab has been tested in a number of small clinical
      trials in multiple sclerosis based on the rationale that blocking CD25 would
      prevent the expansion of autoreactive T lymphocytes. The data from this
      preliminary clinical exploration as well as findings about the mechanism of
      action of anti-CD25 treatment are summarized in this study.

PMID- 18075270
TI  - Natalizumab: targeting alpha4-integrins in multiple sclerosis.
AB  - In 1992, it was shown that monoclonal antibodies blocking alpha(4)-integrins
      prevent the development of experimental autoimmune encephalomyelitis, an animal
      model for multiple sclerosis (MS). As alpha(4)beta(1)-integrin was demonstrated
      to mediate the attachment of immune-competent cells to inflamed brain endothelium
      in experimental autoimmune encephalomyelitis, the therapeutic effect was
      attributed to the inhibition of immune cell extravasation and inflammation in the
      central nervous system. This novel therapeutic approach was rapidly and
      successfully translated into the clinic. The humanized anti-alpha(4)-integrin
      antibody natalizumab demonstrated an unequivocal therapeutic effect in preventing
      relapses and slowing down the pace of neurological deterioration in patients with
      relapsing-remitting MS in phase II and phase III clinical trials. The occurrence
      of 3 cases of progressive multifocal leukoencephalopathy in patients treated with
      natalizumab led to the voluntary withdrawal of the drug from the market. After a
      thorough safety evaluation of all patients receiving this drug in past and
      ongoing studies for MS and Crohn's disease, natalizumab again obtained approval
      in the US and the European Community. A treatment targeting leukocyte trafficking
      in MS has now re-entered the clinic. Further thorough evaluation is necessary for
      a better understanding of the risk-benefit balance of this new treatment option
      for relapsing MS. In this review, we discuss the basic mechanism of action, key
      clinical results of clinical trials and the emerging indication of natalizumab in
      MS.

PMID- 18075272
TI  - Campath-1H treatment of multiple sclerosis.
AB  - Campath-1H is a humanised monoclonal antibody that targets CD52, a cell surface
      protein expressed on lymphocytes, monocytes and eosinophils. A single dose of
      Campath-1H leads to a rapid and profound lymphopenia. Campath-1H has been used in
      Cambridge as an experimental treatment of multiple sclerosis for more than 15
      years. Here, we summarise our clinical and laboratory findings, describing how
      this prototypical 'bench to bedside' therapy continues to inform basic science,
      revealing aspects of the pathogenesis of multiple sclerosis and autoimmunity.

PMID- 18075273
TI  - Positive and negative implications of tumor necrosis factor neutralization for
      the pathogenesis of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a progressive, presumably autoimmune, degenerative
      disease of the central nervous system (CNS). The mechanisms which trigger the
      disease are unknown, but the pathology of MS is caused by the host's own immune
      system, which invades the CNS and attacks the myelin sheath that protects and
      insulates the axons of the nerve cells. Although this inflammatory assault
      selectively destroys myelin, it is believed that the neurological deficits of MS
      are rather the consequence of damage to axons, which occurs secondary to
      inflammation. The inflammatory mediators are generally secreted by myelin
      specific, CD4+ T cells, CD8+ T cells, macrophages and activated glial cells and
      include a large number of cytokines, chemokines and other proinflammatory
      proteins.

PMID- 18075274
TI  - Preclinical assessment of therapeutic antibodies against human CD40 and human
      interleukin-12/23p40 in a nonhuman primate model of multiple sclerosis.
AB  - BACKGROUND: Proinflammatory cytokines, such as interleukin (IL)-12 and IL-23, and
      costimulatory molecules on antigen-presenting cells (APC), such as CD40, are
      critical to autoreactive T cell activation by APC, and hence, are considered
      relevant targets of therapy for immune-mediated inflammatory diseases (IMID).
      OBJECTIVE: The current review discusses the preclinical evaluation of two novel
      immunotherapeutic monoclonal antibodies (mAbs), one directed against human IL
      12/23p40 and the other against CD40. As the antibodies only recognize their
      target molecule in primates, the efficacy could not be tested in rodent models.
      RESULTS: As a preclinical IMID model for the in vivo evaluation of both mAbs, we
      have used the experimental autoimmune/allergic encephalomyelitis (EAE) model in
      common marmoset monkeys (Callithrix jacchus). Both mAbs show beneficial
      activities in the EAE model when administered early in disease development as
      well as after the onset of brain inflammation. The treatment effects were
      evaluated using a combination of quantitative magnetic resonance imaging and a
      series of ex vivo and immunopathological evaluations. CONCLUSION: The promising
      effects during ongoing disease in a relevant preclinical IMID model illustrate
      the potential of these two antibodies as treatment of IMID, in particular for
      multiple sclerosis on which disease EAE has been modeled.

PMID- 18075275
TI  - Familial membranous nephropathy: an X-linked genetic susceptibility?
AB  - BACKGROUND: Membranous nephropathy (MN) is the most common histological diagnosis
      in adults with nephrotic syndrome and a leading cause of end-stage kidney failure
      from glomerulonephritis. Little is known about the underlying aetiology, although
      anti-glomerular antibodies have been implicated. No specific underlying genetic
      defect has yet been identified. METHODS: In a family with four members in three
      generations affected by primary MN, the serum of affected members and their
      mothers were assessed for anti-glomerular antibodies. RESULTS: All four affected
      are male and connected through the maternal line, indicative of X-linked
      inheritance. Age of onset of nephrotic syndrome varied between 1 and 67 years of
      age, suggesting that a potential underlying gene may confer a genetic
      predisposition to MN, but other factors, genetic or environmental, are necessary
      to trigger the disease. Serologic studies revealed antibodies against glomerular
      and peritubular endothelial cells in the mother of the youngest patient.
      CONCLUSIONS: We have identified the largest reported family with a potential X
      linked susceptibility to MN. Foeto-maternal alloimmunization may have triggered
      the disease in the youngest individual. Considering that the majority of patients
      with sporadic MN are male, identification of an X-linked predisposing factor may
      have implications well beyond this family and could provide a target for
      treatment.

PMID- 18075276
TI  - Differences in the glomerular filtration rate calculated by two creatinine-based
      and three cystatin-C-based formulae in hospitalized elderly patients.
AB  - BACKGROUND: Reduced renal function is a health problem in elderly patients.
      Different creatinine- and cystatin-C-based formulae have been used to estimate
      glomerular filtration rate (GFR). AIMS: To investigate individual and group
      differences of GFR estimates derived from five different formulae. METHODS: 60
      patients were randomly assigned to participate in this cross-sectional study.
      Nutrition status was assessed, blood samples were drawn and GFR was calculated
      using two creatinine- and three cystatin-C-based formulae. RESULTS: Four of five
      formulae indicate reduced GFR in >70% of the participants, GFR was significantly
      less in malnourished patients according to one creatinine formula. Estimates from
      the formulae were highly correlated (r = 0.607-0.863, p < 0.001), but individual
      differences were between -36.1 and 79.9 ml/min/1.73 m(2). The formulae grouped
      38.3-60.0% of the subjects differently into the five stages of chronic kidney
      disease. BMI, total cholesterol, age and gender were significant predictors for
      the calculated GFR differences between the formulae. CONCLUSION: The prevalence
      of reduced renal function is high in elderly hospitalized patients. BMI, age
      and/or gender can affect GFR estimates depending on the formula used, and there
      is an association between total cholesterol and calculated GFR differences
      between formulae. Different formulae can result in a different grouping of
      patients into the five stages of chronic renal disease.

PMID- 18075277
TI  - Low CR1 (C3b receptor) level on erythrocytes is associated with poor prognosis in
      hemodialysis patients.
AB  - BACKGROUND: Erythropoietin in patients under dialysis treatment for renal failure
      is low which induces anemia. Treatment with recombinant erythropoietin (rEPO) has
      been used routinely as a supplement treatment for these patients. Immune
      complexes (IC) react with complement and bind to CR1 on erythrocytes (E-CR1), and
      are transported to the liver and/or spleen where IC removal and degradation
      occurs. The erythrocytes then return to circulation where they bind to additional
      IC. There are some patients whose E-CR1 expression is low with chronic anemia in
      spite of rEPO treatment. We hypothesized that in hemodialysis (HD) patients
      altered host defense against infection is associated with low levels of E-CR1. We
      examined if low E-CR1 in dialysis patients constitutes a risk factor for reduced
      host defense and poor outcome. METHODS: In 95 HD patients, E-CR1 was quantified
      using a monoclonal E-CR1 antibody and FACS analysis followed by clinical course
      studies for 5 years. RESULTS: The patients were divided into three groups by E
      CR1 level. Percent survival for the low E-CR1 group (53.3%) was significantly
      lower than the high E-CR1 group (86.4%) (p < 0.01). There were more hepatitis C
      virus-positive patients within the low E-CR1 group (27.3%) than in the high E-CR1
      group (4.7%) (p < 0.05). Furthermore, 10 patients with the lowest E-CR1 levels
      had severe complications, notably infection at an arteriovenous fistula.
      CONCLUSION: A reduced E-CR1 level might be a risk factor for reduced host defense
      and can be used as a predicting factor for poor prognosis in a HD patient.

PMID- 18075278
TI  - Sex-related time-dependent variations in post-stroke survival--evidence of a
      female stroke survival advantage.
AB  - BACKGROUND: Women live longer than men, yet most studies show that gender has no
      influence on survival after stroke. METHODS: A registry was started in 2001, with
      the aim of registering all hospitalized stroke patients in Denmark, and it now
      holds 39,484 patients of which 48% are female. We studied the influence of gender
      on post-stroke mortality, from the time of admission through the subsequent years
      until death or censoring (mean follow-up time: 538 days). All patients underwent
      an evaluation including stroke severity, computed tomography and cardiovascular
      risk factors. Independent predictors of death were identified by means of a
      survival model based on 22,222 individuals with a complete data set. RESULTS:
      Females were older and had severer stroke. Interestingly, the risk of death
      between genders was time dependent. The female/male stroke mortality rate
      favoured women from the first day of stroke and remained so during the first
      month suggesting a female survival advantage. Throughout the second month the
      rate reversed in favour of men suggesting that women in that period are paying a
      'toll' for their initial survival advantage. Hereafter, the rate steadily
      decreased, and after 4 months women continued to have the same low risk as in the
      first week. CONCLUSIONS: Our study suggests a female superiority in stroke
      survival competence.

PMID- 18075279
TI  - Autosomal dominant polycystic kidney disease: recent advances in pathogenesis and
      treatment.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder
      affecting 1 in 1,000 people in the general population and accounts for up to 10%
      of all patients on renal replacement therapy. Numerous fluid-filled epithelial
      cysts arise from different nephron segments as spherical dilatations or small out
      pouchings, enlarge progressively and eventually become disconnected from the rest
      of the renal tubule. The development of cysts is accompanied by destruction of
      the renal parenchyma, interstitial fibrosis, cellular infiltration and loss of
      functional nephrons. ADPKD is not only a kidney disease but also a systemic
      disorder associated with intracranial arterial aneurysms, cardiac valvular
      defects, colonic diverticulosis and cyst formation in other organs such as the
      liver, spleen and pancreas. The identification of PKD1 and PKD2 together with the
      drive to elucidate the functions of their encoded proteins, polycystin-1 (PC1)
      and polycystin-2 (PC2), has led to an explosion of clinical and scientific
      interest in this common disorder. The aim of this review is to highlight recent
      advances in our understanding of ADPKD pathogenesis which are leading to exciting
      new treatment strategies.

PMID- 18075280
TI  - Membrane fluidity and polycystic kidney disease: a hypothesis.

PMID- 18075281
TI  - Growth inhibition of medullary thyroid carcinoma cells by pyrazolo-pyrimidine
      derivates.
AB  - There is no effective treatment for recurrent or metastatic medullary thyroid
      carcinoma (MTC), a tumor arising from thyroid C-cells commonly presenting an
      inherited or acquired RET mutation. In this study we examined the sensitivity of
      two human MTC cell lines to novel pyrazolopyrimidine derivates, able to inhibit
      src-family tyrosine kinase activity. In TT cells [carrying the multiple endocrine
      neoplasia (MEN)2A Ret mutation Cys 634Trp] and MZ-CRC-1 cells (carrying the MEN2B
      RET mutation Met891Thr), one of these compounds, namely Si 34, determined a
      significant growth inhibitory effect (approximately 90% vs control for TT, 80% vs
      control for MZ-CRC-1) mainly due to enhanced cell mortality after a 6-day
      incubation. At concentrations that increased cell mortality, neither biochemical
      or morphological characteristics of apoptosis were detected in TT and MZCRC- 1
      cells treated with Si 34. These results, when confirmed in other in vivo
      preclinical models, suggest that this novel tyrosine kinase inhibitor may be
      useful for the treatment of MTC.

PMID- 18075282
TI  - Plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor
      levels in non-alcoholic steatohepatitis.
AB  - AIM: This study was conducted to demonstrate the plasminogen activator inhibitor-
      1 (PAI-1) and thrombin activatable fibrinolysis inhibitor antigen (TAFI-Ag)
      levels in non-alcoholic steatohepatitis (NASH). MATERIALS AND METHODS: Twenty
      seven patients with biopsy-proven NASH and 18 healthy controls (HC) were
      recruited for the study. Anthropometric data, liver histology (no.=20) and
      laboratory parameters including PAI-1 and TAFI-Ag assessments were recorded.
      RESULTS: When compared with HC, patients with NASH had higher body weight, higher
      waist circumference, elevated blood pressure, higher fasting plasma glucose (FPG)
      levels and higher homeostasis model assessment (HOMA) scores. The mean plasma PAI
      1 levels of patients was found to be higher than HC (87.60 ng/ml vs 30.84 ng/ml
      p=0.000) and mean plasma TAFI-Ag levels of patients was found to be significantly
      lower (8.69 microg/ml vs 12.19 microg/ml p=0.000). PAI-1 levels were correlated
      with systolic blood pressure, age, body weight, transaminases, waist
      circumference, FPG, body mass index, and HOMA score. TAFI-Ag levels were found to
      be negatively correlated with transaminases, waist circumference, and body
      weight. In multiple regression analysis, BMI was the independent variable
      effecting PAI-1 levels. We did not show any association between PAI-1, TAFI-Ag,
      disease activity score and fibrosis score. HOMA was the independent variable
      effecting liver fibrosis in our patients. CONCLUSION: In this study we
      demonstrated that patients with biopsy-proven NASH had higher PAI-1 and lower
      TAFI-Ag expression than HC. Elevated levels of PAI-1 in NASH is the consequence
      of insulin resistance state. Lower TAFI-Ag levels may be related to the
      overactivation of TAFI pathway resulting in TAFI-Ag depletion. Furthermore, liver
      function disturbances may impair TAFI production in NASH. We also showed that
      NASH patients even with slight elevations of transaminases feature marked insulin
      resistance and components of metabolic syndrome.

PMID- 18075283
TI  - Total ghrelin levels during acute insulin infusion in patients with polycystic
      ovary syndrome.
AB  - Controversial data were reported concerning fasting ghrelin (decreased, normal or
      elevated) in polycystic ovary syndrome (PCOS). The aim of our study was to
      clarify ghrelin levels in non-obese, overweight, and obese PCOS patients; to
      investigate the effect of acute insulin infusion on ghrelin in PCOS as a chronic
      insulin-resistant state, with and without the impact of obesity, and to examine
      ghrelin-androgen interaction. In that order, we evaluated 1) ghrelin levels among
      8 nonobese patients with PCOS [body mass index (BMI): 20.52+/-1.31 kg/m2], 8
      overweight and obese patients with PCOS (BMI: 34.36+/-6.53 kg/m2) and their
      respective controls, 2) ghrelin suppression during euglycemic hyperinsulinemic
      clamp, and 3) ghrelin-androgen interrelationship. After overnight fast, 2-h
      euglycemic hyperinsulinemic clamp, was performed in all investigated women.
      Fasting ghrelin was significantly lower in non-obese PCOS than in controls
      (64.74+/-25.69 vs 108.36+/-52.60; p<0.05) as well as in overweight and obese PCOS
      in comparison with controls (38.71+/-14.18 vs 98.77+/-40.49; p<0.05). Insulin
      infusion significantly suppressed ghrelin in all subgroups of investigated women.
      Analysis of variance for repeatable measures confirmed that there was no
      significant difference in pattern of response between PCOS and controls. In
      conclusion, women with PCOS had lower fasting ghrelin and decreased insulin
      sensitivity independently of their BMI, compared to the controls. In addition,
      there were no differences between fasting ghrelin levels among non-obese,
      overweight, and obese women with PCOS. During euglycemic hyperinsulinemic clamp,
      ghrelin decreased in all studied groups to a similar extent, implying that,
      compared to chronic hyperinsulinemia, acute hyperinsulinemia reduces ghrelin
      levels independently of the degree of insulin resistance.

PMID- 18075284
TI  - Evaluation of proopiomelanocortin mRNA in the peripheral blood from patients with
      Cushing's syndrome of different origin.
AB  - ACTH-dependent Cushing's syndrome is due to ACTH overproduction originating from
      a pituitary corticotroph adenoma (Cushing's disease) or from ectopic tumors
      (ectopic ACTH syndrome). Due to difficulties in the differential diagnosis
      between these two forms of hypercortisolism it would be important to have
      molecular tools able to discriminate the two conditions. It is known that
      proopiomelanocortin (POMC) gene transcription can originate messengers of
      different length. ACTHomas show the normal 1072 nucleotides (nt) transcript,
      whereas ectopic tumors seem to be associated with a longer mRNA form (1450 nt).
      In order to analyse the presence of different POMC transcripts, we extracted
      total RNA from peripheral lymphocytes of 10 patients with Cushing's disease, 10
      with ectopic Cushing syndrome, and 20 controls as well as from pituitary tissues
      (2 ACTH-omas and a normal pituitary polyA+ sample). Northern blot analysis
      correctly revealed a 1072 nt mRNA molecule in pituitary ACTH-oma and in the
      normal pituitary polyA+ RNA samples, whereas neither this molecule nor other
      alternative transcripts were detected in blood samples from patients and
      controls. These data were confirmed by the more sensitive RT-PCR technique. This
      study further underlines the need for alternative approaches in the diagnosis of
      ACTH-dependent Cushing's syndrome.

PMID- 18075285
TI  - Physiological dose of lycopene suppressed oxidative stress and enhanced serum
      levels of immunoglobulin M in patients with Type 2 diabetes mellitus: a possible
      role in the prevention of long-term complications.
AB  - OBJECTIVE: This study was undertaken to evaluate the antioxidant effects of
      lycopene in physiological doses and its possible effects on the immune response
      in patients with Type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: A
      total of 35 patients with T2DM of both sexes aged 54+/-9 yr were enrolled in a
      double-blind placebo-controlled clinical trial conducted for 2 months. After a 2
      week lycopene-free diet washout period, patients were allocated to either
      lycopene supplementation group (10 mg/day) (no.=16) or placebo group (no.=19),
      which were age- and sex matched. Patients were instructed to keep their diet and
      physical activity as unchanged as possible. RESULTS: While dietary intake of
      energy and body weight did not change, the ratio of serum total antioxidant
      capacity (TAC) to malondialdehyde (MDA) increased significantly in the lycopene
      group compared to the placebo group (p=0.007). Though a statistically significant
      increase in serum concentrations of lycopene (p<0.001) was not accompanied by
      enhanced delayed-type hypersensitivity response, a significant negative
      correlation was found between serum levels of lycopene and immunoglobulin (Ig)G
      (r=-0.338, p=0.008). Interestingly, variations of serum levels of lycopene
      directly correlated with those of IgM (r=0.466, p=0.005). There was an
      insignificant decrement in serum anti-oxidized LDL IgG levels in the lycopene
      group. CONCLUSIONS: Lycopene, probably by increasing TAC and inhibiting MDA-LDL
      formation, may attenuate T cell-dependent adaptive (pro-atherogenic) immune
      response. Meanwhile, with enhancement of innate immunity and hence prevention of
      ox-LDL uptake by macrophage and foam cell formation, lycopene may be effective in
      prevention of long-term diabetic complications, notably cardiovascular disease.

PMID- 18075286
TI  - Sequencing of the entire coding region of the receptor associated protein (RAP)
      in patients with primary hypothyroidism of unknown origin.
AB  - The LDL receptor-associated protein (RAP) is involved in secretion of
      thyroglobulin (Tg) from the thyrocyte to the colloid. Disruption of the RAP gene
      in mice results in a reduced Tg content within the colloid, leading to
      subclinical hypothyroidism and histological alterations resembling early goiter.
      Here we studied the entire coding sequence of RAP in genomic DNA samples from 18
      patients with primary hypothyroidism not due to thyroid autoimmunity or
      dysgenesis. The control group included 21 subjects with no evidence of thyroid
      alterations. Eleven different polymorphisms with amino-acid substitution and 4
      different missense polymorphisms without amino-acid substitution were found in
      various regions of the RAP gene. Only one polymorphism in exone 7 (V311M) was
      observed exclusively in patients, but it had been previously reported in normal
      subjects as well. The remaining polymorphisms were found either both in patients
      and controls or only in controls and had not been previously reported. The
      frequency of the various polymorphisms did not differ significantly between
      patients and controls. Based on these findings, we conclude that alterations of
      the RAP gene are not a common cause of hypothyroidism, although it cannot be
      excluded that other, rarer alterations with a pathogenic effect exist, and that
      they should be investigated in a larger number of patients.

PMID- 18075287
TI  - Critical assessment of the current guidelines for the management and treatment of
      morbidly obese patients.
AB  - An interdisciplinary panel of specialists met in Mallorca in the first European
      Symposium on Morbid Obesity entitled; "Morbid Obesity, an Interdisciplinary
      Approach". During the two and half days of the meeting, the participants
      discussed several aspects related to pathogenesis, evaluation, and treatment of
      morbid obesity. The expert panel included basic research scientists, dietitians
      and nutritionists, exercise physiologists, endocrinologists, psychiatrists,
      cardiologists, pneumonologists, anesthesiologists, and bariatric surgeons with
      expertise in the different weight loss surgeries. The symposium was sponsored by
      the Balearic Islands Health Department; however, this statement is an independent
      report of the panel and is not a policy statement of any of the sponsors or
      endorsers of the Symposium. The prevalence of morbid obesity, the most severe
      state of the disease, has become epidemic. The current recommendations for the
      therapy of the morbidly obese comes as a result of a National Institutes of
      Health (NIH) Consensus Conference held in 1991 and subsequently reviewed in 2004
      by the American Society for Bariatric Surgery. This document reviews the work-up
      evaluation of the morbidly obese patient, the current status of the indications
      for bariatric surgery and which type of procedure should be recommended; it also
      brings up for discussion some important real-life clinical practice issues, which
      should be taken into consideration when evaluating and treating morbidly obese
      patients. Finally, it also goes through current scientific evidence supporting
      the potential effectiveness of medical therapy as treatment of patients with
      morbid obesity.

PMID- 18075288
TI  - The impact of thyroidectomy on psychiatric symptoms and quality of life.
AB  - INTRODUCTION: Existing trials investigated the impact of medical treatment of
      thyroid disorders on health-related quality of life (QOL) and psychiatric
      symptoms. The aim of this prospective study is to analyze the impact of thyroid
      surgery on QOL and severity of psychiatric symptoms. MATERIALS AND METHODS: Forty
      seven patients undergoing thyroid surgery (TS) were assessed before thyroidectomy
      (T0) and 37 also after surgery, >or=6 months after euthyroidism was achieved
      (T1). QOL and psychiatric symptoms were evaluated at T0 and T1 using the Medical
      Outcomes Study Short Form Survey (SF-36) and the Symptom Checklist-90 (SCL-90-R).
      Scores at T0 were compared with those of patients undergoing surgery for non
      thyroidal disease and the SF-36 scores were also compared with the normative
      Italian sample. Changes in QOL and psychiatric symptoms between T0 and T1 were
      also examined. RESULTS: Health-related QOL in TS patients before surgery was
      poorer than in the comparison group on the SF-36 mental component summary measure
      and social functioning. Mental health improved significantly after surgery but
      social functioning remained markedly impaired. A significant reduction in the
      severity of psychiatric symptoms was observed. DISCUSSION: Our results indicate
      that even long after euthyroidism is achieved after surgery, patients show a
      significant improvement of mental health and a reduction of psychiatric symptoms.
      Nevertheless, patients continue to have a poorer QOL compared to the Italian
      normative sample.

PMID- 18075289
TI  - Association of the +33371 A/G polymorphism in adiponectin receptor 2 gene with
      Type 2 diabetes in the Chinese population.
AB  - PURPOSE: The aim of this study was to investigate the association between the
      +33371 A/G polymorphism of adiponectin receptor 2 gene and the risk of Type 2
      diabetes (T2DM) in the Chinese population. METHODS: A case-control study was
      performed among 594 unrelated Chinese people. All of them underwent a
      standardized assessment on phenotypic characterization including anthropometry,
      75-g oral glucose tolerance test with insulin levels, fasting serum total
      cholesterol, and fasting serum triglyceride. The +33371 A/G polymorphism was
      detected by PCR-restriction fragment length polymorphism. RESULTS: The PCR
      products after digestion displayed 3 genotypes, including AA, AG, and GG. The
      frequencies of AA, AG, and GG genotypes in T2DM group (no.=261) and control group
      (no.=353) were 0.379, 0.414, 0.207 and 0.162, 0.541, 0.297, respectively. There
      was a significant difference in both genotypic and allelic frequencies
      distribution of +33371 A/G polymorphism between T2DM and control subjects
      (p<0.001). Subjects with AA+AG genotypes showed higher levels of fasting plasma
      glucose (p=0.024), fasting serum triglycerides (p=0.036), and body mass index
      (BMI) (p=0.013) than those with GG genotype in the T2DM group but not in the
      control group. Compared with GG genotype, AA (p<0.001) and AA+AG (p=0.002)
      genotype group had a significantly higher risk of T2DM, with odds ratio (OR) for
      2.290 [95% confidence interval: 1.482-3.359] and 1.963 (1.183-2.997). Compared
      with AG+GG genotype group, the risk of T2DM in AA genotype increased slightly
      (p=0.007), with OR for 1.478 (1.025-2.036). CONCLUSION: The present findings
      suggest that +33371 A/G polymorphism is associated with increased risk of T2DM
      and multiple insulin resistance-related phenotypes (including fasting plasma
      glucose, fasting serum triglycerides, and BMI) in the Chinese population.

PMID- 18075290
TI  - Proteomic analysis of human thyroid fine needle aspiration fluid.
AB  - The aim of this study was to determine the protein pattern of human thyroid fine
      needle aspiration fluid (FNA) using a proteomic approach. FNA proteins were
      separated using 2-dimensional gel electrophoresis (2DE), digested and then
      analyzed by peptide mass fingerprinting. For the first time, we provided an image
      of the protein components of the FNA, in which approximately 220 protein spots
      can be identified. The proteome analysis revealed a specific fingerprint of FNA
      with proteins appertaining to various functional systems. Our preliminary results
      of FNA protein pattern could be a starting point in studying the presence of
      potential markers implicated in thyroid diseases.

PMID- 18075291
TI  - An additional child case of an aldosterone-producing adenoma with an atypical
      presentation of peripheral paralysis due to hypokalemia.
AB  - Aldosterone-producing adenoma, which is characterized by hypertension,
      hypokalemia, and elevated aldosterone levels with suppressed plasma renin
      activity, is a rare condition during childhood and is also potentially curable.
      To the best of our knowledge, nearly 25 cases of childhood aldosterone-secreting
      adenoma have been reported in the literature to date. Here we describe a 13-yr
      old girl with primary hyperaldosteronism secondary to aldosterone-secreting
      adenoma. The patient was admitted to our hospital with the neuromuscular
      complaints of muscle weakness and inability to walk due to hypokalemia. She had
      been misdiagnosed as having hypokalemic periodic paralysis 2 months before
      admission and her symptoms had radically improved with potassium supplementation.
      However, her blood pressure levels had increased and her symptoms reappeared 2
      days prior to being observed during hospitalization in our institution.
      Laboratory examinations revealed hypokalemia (2.1 mEq/l), and increased serum
      aldosterone levels with suppressed plasma renin activity. Abdominal
      ultrasonography and abdominal magnetic resonance imaging revealed left adrenal
      mass. Laparoscopic adrenalectomy was performed and histopathological examinations
      showed benign adrenal adenoma. Serum aldosterone levels and blood pressure levels
      returned to normal after surgical intervention. This case demonstrates the
      importance of a systemic evaluation including blood pressure monitorization of
      children with hypokalemia as intermittent hypertension episodes may be seen;
      cases without hypertension may be misdiagnosed as rheumatological or neurological
      disorders such as hypokalemic periodic paralysis, as in our case.

PMID- 18075292
TI  - Gestational diabetes, inflammation, and late vascular disease.
AB  - Physiological changes of pregnancy include insulin resistance and activation of
      the innate immunity with an inflammatory response. The working hypothesis is that
      the sub-clinical inflammation associated with excessive adiposity may favor the
      development of gestational diabetes (GDM) and Type 2 diabetes and other metabolic
      abnormalities related to cardiovascular disease later in life. In this paper we
      review the complex interrelationship among inflammatory markers, metabolic
      syndrome, and endothelium dysfunction in women with GDM and discuss if women with
      previous GDM (pGDM) could be considered at risk for cardiovascular diseases.
      MEDLINE was searched for articles relating GDM and the adipokines (tumor necrosis
      factor-alpha and adiponectin) as well as the acute-phase inflammatory biomarker C
      reactive protein that contribute to the development of diabetic pregnancy and
      vascular complications. However, to date, in pGDM women no prospective study is
      available, to corroborate the hypothesis that inflammatory pattern could be taken
      as predictor of cardiovascular disease later in life. Therefore, our paper should
      provide arguments to perform follow-up programs to prevent cardiovascular events
      in women with pGDM. Control of body weight, regular physical exercise are indeed
      powerful intervention tools able at improving insulin sensitivity and reduce sub
      clinical inflammation, both involved in the pathogenesis of cardiovascular
      disease.

PMID- 18075293
TI  - Which patients with sexual dysfunction are suitable for testosterone replacement
      therapy?
AB  - According to all the consensus and statements of the major societies,
      hypogonadism should be considered a medical problem, termed late onset
      hypogonadism (LOH) or testosterone deficiency syndrome (TDS), only when symptoms
      are present. One of the most common symptoms of LOH/TDS is sexual dysfunction
      (SD). The main purpose of this review is to discuss the role of testosterone (T)
      in men's sexual function, including epidemiology, pathophysiology, diagnostic
      procedures, and treatment efficacy in patients affected by erectile dysfunction
      (ED). The prevalence of hypogonadism in men with ED ranges from 1.7% to 35%. In
      ED patients, hypogonadism is often associated with reduced sexual desire and
      nocturnal penile erections, while association with sex-induced erection is less
      evident. This is because T regulates not only cyclic guanosine monophosphate
      (cGMP) formation, through nitric oxide synthase (NOS) stimulation, but also its
      catabolism, through phosphodiesterase-5 (PDE5) activity. The androgen-dependent
      PDE5 expression could explain the reduced effectiveness of PDE5 inhibitors
      (PDE5i) in the treatment of erectile dysfunction in hypogonadal patients.
      Accordingly, T substitution in these subjects restores responsiveness to PDE5i.
      Recognising hypogonadism in patients with ED is essential in order to
      appropriately treat the disease. However, suspecting LOH/TDS in SD patients is
      not an easy task. Recently published structured inventories, such as ANDROTEST,
      might help physicians to recognize hypogonadism and to further pursue its
      appropriate diagnosis and treatment.

PMID- 18075295
TI  - Upregulation of Beclin 1 in the ischemic penumbra.
AB  - Here we discuss the probable role of autophagy in cerebral ischemia based on our
      own recent data and the literature. We examined the protein level of Beclin 1
      (Bcl-2 interacting protein) and microtubule-associated protein 1 light chain 3
      (LC3) which were previously found to promote autophagy. We found a dramatic
      elevation in Beclin 1 levels and LC3 in the penumbra of rats challenged by
      cerebral ischemia. We found also that a subpopulation of Beclin 1-upregulating
      cells is also expressing the active form of caspase-3, and that all Beclin 1
      upregulating cells display dense staining of LC3. Neuronal cells that overexpress
      Beclin 1 may exhibit damaged DNA but without changes in nuclear morphology, which
      indicates that not all the Beclin 1-upregulating cells are predestined to die. We
      conclude that the cell death in the penumbra bears a resemblance not only to
      necrosis, apoptosis, or a compromise between the two, but exhibits also
      biochemical and morphological characteristics of autophagic cell death. The
      question that constantly arises, however, is whether autophagic activity in
      damaged cells is the cause of death or is actually an attempt to prevent it as a
      part of an endogenous neuroprotective response.

PMID- 18075296
TI  - Controlled internalization of Her-2/ neu receptors by cross-linking for targeted
      delivery.
AB  - Receptor mediated internalization is a crucial step for targeted intracellular
      delivery of therapeutic and imaging agents. It was recently demonstrated that
      trastuzumab, an FDA approved humanized monoclonal antibody against Her-2/ neu
      tyrosine kinase receptor, did not induce endocytosis of the internalization
      resistant Her-2/ neu receptor. Here we report that accelerated internalization of
      trastuzumab can be induced by cross-linking the cell membrane bound antibody
      receptor complex with an avidin/streptavidin-biotin system. We demonstrated that
      internalization was achieved both in vitro and in vivo in Her-2/ neu expressing
      human breast cancer cell lines (BT-474, SK-BR-3 and AU-565) and that repetitive
      labeling cycles further amplified the loading of cargo molecules within the
      targeted cells. No trastuzumab binding and internalization was observed in Her-2/
      neu negative MDA-MB-231 cells, whereas weak membrane binding and negligible
      internalization were detected in MCF-7 cells with low expression level of Her-2/
      neu receptor. The method was used to noninvasively image Her-2/ neu receptors in
      isolated cells and in a preclinical breast cancer model with MRI. The controlled
      internalization of Her-2/ neu receptors can potentially enhance intracellular
      delivery of drugs and imaging probes, and improve imaging sensitivity and
      selectivity as well as therapeutic efficacy, through antibody-directed binding
      and internalization using a pretargeting approach.

PMID- 18075294
TI  - Somatostatin receptor scintigraphy in thoracic diseases.
AB  - Somatostatin (SS) receptor scintigraphy is useful for the diagnosis of lesions
      with high density of SS receptors, and above all neuroendocrine tumors. For
      several years, only indium-labeled octreotide has been applied to visualise in
      vivo tissues with SS receptor overexpression. Radiolabeled octreotide became the
      gold standard for the detection of neuroendocrine tumors. More recently, however,
      several new SS analogues with varying affinity for SS receptor subtypes have been
      developed, and different radionuclides as radiolabels have been introduced.
      Moreover, significant improvements have been made by the introduction of hybrid
      machines, such as single photon emission computed tomography/ computed tomography
      (SPECT/CT) or positron emission tomography (PET)/CT that enable to perform whole
      body imaging quickly and with high anatomical resolution in several body areas,
      including the chest. The development of more specific radiopharmaceuticals,
      together with the modern technique of imaging, may provide excellent quality
      images with high contrast, allowing to depict very small lesions and making them
      easy to interpret. Indeed, in the management of SS receptor-positive lesions, the
      contribution of nuclear medicine is essential in several clinical settings, such
      as initial diagnosis, disease staging, follow-up, treatment planning, and
      treatment monitoring. In addition, the tracer uptake might be used as a
      prognostic parameter and as a predictor of treatment response. In the chest,
      apart in (neuro)endocrine tumors, SS receptors have been demonstrated in
      granulomatous diseases, like sarcoidosis and other immune-mediated disorders,
      such as anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. In
      this paper we review and discuss the role of SS receptor scintigraphy in
      diagnosis, staging or follow- up of thoracic SS receptor-positive lesions.

PMID- 18075297
TI  - PPARgamma-active triterpenoid CDDO enhances ATRA-induced differentiation in APL.
AB  - Acute promyelocytic leukemia (APL) is associated with oncogenic PML-RARalpha that
      acts as a dominant negative transcriptional repressor of retinoic acid (RA)
      receptor target genes by recruiting histone deacetylase (HDAC). The peroxisome
      proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear
      receptor family that forms heterodimers with retinoid X receptor (RXR). In
      addition to RAR targets, PML-RARalpha silence a wide range of nuclear receptor
      target genes including PPARgamma targets. All-trans-retinoic acid (ATRA), a
      ligand for the RA receptor (RAR), restores normal retinoid signaling and induces
      terminal differentiation of APL cells; however, APL cells can develop resistance
      to ATRA. Using ATRA sensitive NB4 and ATRA-resistant derivative MR2 cell lines,
      we demonstrate that PPARgamma ligand 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic
      acid (CDDO) enhances pro-apoptotic and differentiating effects of ATRA in ATRA
      sensitive NB4 cells and partially reverses ATRA resistance in MR2 cells. The
      CDDO/ATRA combination synergistically induces RARbeta2 expression both in ATRA
      sensitive and -resistant APL cells. RARbeta2 MrNA induction by CDDO/ATRA was
      mediated in part by enhanced H3-Lys9 acetylation in the RARbeta2 promoter which
      in turn increased the affinity of RARbeta for betaRARE. PPARgamma specific
      inhibitor T007 and silencing of PPARgamma by siRNA diminished CDDO-induced
      maturation and RARbeta2 mRNA along with PPARgamma induction indicating that
      PPARgamma activation is at least partially responsible for the RARbeta2
      transcription and maturation induction. In an in vivo mouse model of APL, CDDO
      derivative CDDO-methyl ester markedly enhanced ATRA-induced maturation and
      extended the survival of mice. In summary, these results provide rationale for
      the combined targeting of RAR and PPARgamma nuclear receptors in the therapy of
      APL.

PMID- 18075298
TI  - Primary cardiac lymphoma: utility of multimodality imaging in diagnosis and
      management.
AB  - Primary cardiac lymphoma (PCL) is an extremely rare disease defined as a lymphoma
      strictly confined to the heart or pericardium without dissemination. We present
      the case of an 82 yr old male with newly diagnosed PCL and two years of
      subsequent follow up. This report highlights the utility of a multimodality
      imaging approach in the diagnosis and management of PCL.

PMID- 18075299
TI  - Erythropoietin reduces cisplatin-induced apoptosis in renal carcinoma cells via a
      PKC dependent pathway.
AB  - Anaemia which develops as a consequence of malignancies is often treated using
      recombinant human erythropoietin (rhEpo). Epo is now known as an anti-apoptotic
      factor for a wide range of cell types that express Epo receptors (EpoRs) and its
      co-use with cancer therapies can act detrimentally to diminish therapy-induced
      apoptosis. This had not been analyzed for renal cell carcinomas (RCCs). We
      examined the influence of rhEPO on the ability of cisplatin to induce apoptosis
      in RCCs. Two RCC cell lines (SN12K1 and ACHN) were compared with a non-RCC renal
      epithelial cell line (HK2). Cells were treated with 50 microM cisplatin with and
      without 200 IU/mL rhEpo and were compared for apoptosis, mitosis and protein
      expression of EpoR, nuclear factor-kappaB (NFkappaB), protein kinase C (PKC), Bcl
      2, Bax and cyclin-D1. Experiments were repeated with PKC promotion (PMA, 20 nM)
      or inhibition (H7, 10 microM). rhEpo reduced cisplatin-induced apoptosis in RCCs
      (p < 0.01), compared with HK-2s. EpoR expression was increased only in SN12K1
      with rhEpo, with and without cisplatin. NFkappaB, Bax and Bcl-2 expression was
      unchanged. PKC protein expression was significantly reduced in cisplatin-treated
      RCCs with rhEpo, correlating with reduced apoptosis. When the PKC pathway was
      inhibited in these cells, levels o apoptosis returned to normal for cisplatin
      treatment, indicating activation of the PKC pathway by rhEpo. PMA promotion
      increased mitosis only in the RCCs, with and without rhEpo (p < 0.05). In
      summary, rhEPO reduced cisplatin-induced apoptosis of RCCs and promoted their
      mitosis via PKC-dependent pathways. This information indicates caution for use of
      rhEpo in RCC patients for anemias.

PMID- 18075300
TI  - SEPT9_V1 protein expression is associated with human cancer cell resistance to
      microtubule-disrupting agents.
AB  - SEPT9 is a mammalian septin family member. There is growing evidence that SEPT9
      plays a role in cancer. The protein product, SEPT9_V1, associates with
      microtubules and interacts with hypoxia-inducible factor (HIF)-1alpha, the
      regulated subunit of the key transcription factor HIF-1. HIF-1 transcriptional
      activity is thoroughly dependent on intact microtubules. We tested the hypothesis
      that SEPT9_V1 confers resistance to microtubule-mediated HIF-1 inhibitors.
      SEPT9_V1 protein expression was strongly correlated with susceptibility of a wide
      range of cancer cells to 2-methoxyestradiol and paclitaxel. Our results revealed
      that SEPT9_V1 could serve as a biomarker for therapeutic resistance to
      microtubule disrupting agents.

PMID- 18075301
TI  - 1E10 anti-idiotype vaccine in non-small cell lung cancer: experience in stage
      IIIb/IV patients.
AB  - Conventional treatment of non-small cell lung cancer (NSCLC) has apparently
      reached a plateau of effectiveness in improving the survival of the patients. For
      that reason the search for new therapeutic strategies in this type of tumor is
      justified. 1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific
      to P3 Ab1 MAb, which reacts with NeuGc-containing gangliosides, sulfatides and
      with antigens expressed in some tumors, including those from the lung. We report
      the treatment with aluminum hydroxide-precipitated 1E10 MAb of 34 stage IIIb and
      37 stage IV NSCLC patients. These patients were treated with the anti-idiotype
      vaccine, after received standard chemotherapy and radiotherapy, in a
      compassionate-use basis study. Patients received five bi-weekly injections of 1
      mg of 1E10/Alum, other 10 doses at 28-day intervals and later the patients who
      maintained a good performance status continued to be immunized at this same time
      interval. No evidence of unexpected or serious adverse effects was reported. The
      median survival time of the 56 patients who entered the study with partial
      response or disease stabilization and with a PS 1 after the first line of
      chemo/radiotherapy, was 11.50 months from starting vaccination. In contrast, the
      median survival time calculated for patients who started vaccination with
      progressive disease and/or a PS2 was 6.50 months.

PMID- 18075302
TI  - PDGF BB induces VEGF secretion in ovarian cancer.
AB  - We identified the platelet derived growth factor receptor (PDGFR) as a potential
      target in epithelial ovarian carcinoma (EOC). This led us to test whether
      inhibition of the PDGFR affects ovarian cancer cell proliferation and survival
      and regulates other processes critical to tumor growth and metastasis. We
      postulated that there is a correlation between the PDGF-PDGFR axis and the
      secretion of VEGF in EOC. VEGF secretion in ovarian tumors, cancer cells, serum
      and ascites fluid was measured by IHC, Western Blot and ELISA. We found increased
      VEGF expression and secretion in most ovarian tumors (by IHC), in EOC malignant
      ascites and in the conditioned media of primary ovarian cancer cells (quantified
      by ELISA). In malignant ascites, the levels of secreted PDGF BB and VEGF were
      strongly correlated (Pearson coefficient of correlation R = 0.728), suggesting
      that the two pathways interconnect. In PDGFR expressing immortalized ovarian
      cancer cells, PDGF potently induced VEGF secretion, while imatinib mesylate
      (Gleevec), a partially selective PDGFR inhibitor, reduced PDGF stimulated VEGF
      production to basal state. In ovarian cancer cells overexpressing constitutively
      active Akt, imatinib inhibited partially VEGF secretion, suggesting that the
      PI3K/Akt pathway is implicated in PDGF-stimulated VEGF secretion. In summary,
      these results suggest a correlation between the PDGF and VEGF networks in ovarian
      cancer cells and tumors. The effects of imatinib on VEGF secretion in tumor cells
      may affect the tumor microenvironment in a manner detrimental to tumor
      progression.

PMID- 18075303
TI  - Cellular differentiation in three-dimensional lung cell cultures.
AB  - INTRODUCTION: Aspects of human biology that are not sufficiently addressed by
      current cell culture models are cellular differentiation and three-dimensional (3
      D) structural organization. A model that more closely associates the presence and
      biology of organelles to molecular expressions relevant to these organelles may
      provide evidence of cellular differentiation and the beginning steps in the
      construction of a 3-D architecture. The development of a new model--3-D cell
      cultures--may ultimately provide a better understanding of lung biology and
      pathobiology. PURPOSE: The purpose of this study was to develop both traditional
      monolayer and 3-D cell cultures of a known and well documented normal lung cell
      line and then to determine similarities and differences between these cultures in
      terms of differentiation and molecular marker expression. RESULTS: Electron
      microscopy identified presence of lipid inclusion, microvilli, extra cellular
      matrix, and tight junctions in the 3-D cultures; differentiation not seen in ML
      cultures. The degree of differentiation determined by immunohistochemistry when
      the cell line was grown as ML or 3-D cultures shows that ultra-structure and
      marker expressions were more representative of control tissue than when cells
      were grown in 3-D than as MLs. METHODS: An immortalized cell line was grown as a
      traditional monolayer (ML) in culture flasks and as 3-D cultures in rotating
      walled vessels and incubated under identical conditions. Comparison for presence
      of differentiation and marker expression between these cultures and control
      tissue collected from surgical patient specimens was studied. Electron microscopy
      for identification of ultra structures, and immunohistochemistry (ZO-1, EMA, ICAM
      1, villin, tubulin, CK 18, VWF, Collagen IV and human mucin) for phenotypic
      comparisons between cells in ML and 3-D cell cultures was conducted. SUMMARY: The
      development of 3-D cell cultures will provide for a new and more powerful tool in
      the study of lung biology and pathobiology.

PMID- 18075304
TI  - Differential response of human glioblastoma cell lines to combined camptothecin
      and ionizing radiation treatment.
AB  - In order to enhance the cytotoxicity of radiation, camptothecin (CPT), an
      inhibitor of DNA topoisomerase I, was added to the cultured glioma cell lines
      before irradiation (IR). Radiation responses of five glioblastoma cell lines (U87
      MG, U373-MG, GHE, GaMG and SNB-19) treated with CPT were analyzed in terms of
      cell and colony counts, cell cycle progression, expression of histone gamma H2AX,
      DNA repair protein Rad50, survivin, cleaved caspase 3, p53 and of topoisomerase
      I. CPT enhanced the radiotoxicity in U87-MG and SNB-19 cell lines if cell and
      colony counts were used as the end-points. In contrast, pre-treatment with CPT of
      U373-MG, GHE and GaMG cell lines did not enhance cytotoxicity of IR in terms of
      cell and colony counts but accelerated DNA damage repair assessed by Rad50 foci.
      CPT treated glioma cells revealed at least two subpopulations with respect to the
      expression of histone gamma H2AX, a marker of DNA double-strand breaks. The cell
      lines tested also differed in the expression of survivin, cleaved caspase 3, p53
      and of topoisomerase I. The failure of CPT to enhance the radiotoxicity of glioma
      U373-MG, GHE and GaMG cell lines in terms of cell and colony counts was found to
      correlate with accelerated DNA damage repair, and with low expression of
      topoisomerase I, a target of CPT.

PMID- 18075305
TI  - Synergistic effect of mTOR inhibitor rapamycin and fluorouracil in inducing
      apoptosis and cell senescence in hepatocarcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide
      with an annual occurrence of one million new cases. At present there is no
      effective treatment for HCC individuals that not amenable to curative therapies.
      Recent studies show the PI3K/Akt/mTOR signal pathway is involved in multiple
      cellular functions including proliferation, differentiation, tumorigenesis, and
      apoptosis. Rapamycin (a specific Mtor inhibitor) could lead to G(1) arrest of
      many malignant cell lines, and currently analogs of rapamycin are being
      investigated as a cancer chemotherapeutic adjuvant. This study investigated
      rapamycin and chemotherapeutic agent 5-fluorouracil (5-Fu) in combination
      treatment induced apoptosis and cell senescence in hepatocarcinoma cell line SMMC
      7721 cells. Treating SMMC-7721 cells with rapamycin plus 5-Fu led to not only
      apoptosis but also cell senescence, and the senescent cells exhibited
      significantly less clonogenic potential than 5-Fu individually treated cells.
      Further study showed rapamycin plus 5-Fu-induced senescence-like growth arrest
      was accompanied by down-regulation of AP-1 and NF kappa B transcription activity.
      These results suggest that inhibitors of mTOR may have anticancer potential when
      used together with some other chemotherapeutic agents, and that down-regulation
      of AP-1 and NF kappa B transcription activity might take part in a senescence
      like growth arrest program induced by rapamycin plus 5-Fu.

PMID- 18075306
TI  - Antibacterial, antifungal, and anticancer activities of volatile oils and
      extracts from stems, leaves, and flowers of Eucalyptus sideroxylon and Eucalyptus
      torquata.
AB  - Eucalyptus species leaves have been traditionally used to heal wounds and fungal
      infections. Essential oils and extracts of some Eucalyptus species possess
      antimicrobial and antitumor properties. We sought to determine antimicrobial and
      cytotoxic activities of oils and extracts of leaves, stems, and flowers of
      Eucalyptus sideroxylon and Eucalyptus torquata grown in Egypt. An agar diffusion
      method was used to analyze antimicrobial activities of essential oils and
      extracts of Eucalyptus against medically important gram-positive and gram
      negative bacteria. A sulphorhodamine B assay was used to analyze the in vitro
      cytotoxic activities of oils and extracts against Human hepatocellular carcinoma
      cell line (HEPG2), and Human breast adenocarcinoma cell line (MCF7). Gram
      positive bacteria were highly susceptible to oils and extracts of both Eucalyptus
      species. With the exception of Escherichia coli, gram-negative bacteria were
      resistant to extracts, but susceptible to the oil obtained from at least one
      organ of E sideroxylon and E torquata. Although Aspergillus flavus and
      Aspergillus niger were resistant to the extracts, essential oils of E sideroxylon
      and E torquata generally exhibited moderate to high antifungal activities against
      Candida albicans, A flavus and A niger. Oils of E torquata stems exhibited
      cytotoxic activities on MCF7 cells followed by oils of E torquata leaves and E
      sideroxylon leaves. However, oils from both species failed to exert cytotoxic
      effects on HEPG2 cells. This is the first report of antimicrobial and antitumor
      properties of E sideroxylon and E torquata. Results suggest a wider use of
      Eucalyptus species products in pharmaceutical, cosmetic, and food preparations.

PMID- 18075307
TI  - Synergy of Pancratistatin and Tamoxifen on breast cancer cells in inducing
      apoptosis by targeting mitochondria.
AB  - Pancratistatin (PST), a natural compound obtained from the Hawaiian spider lily,
      is known to be specific and selective in inducing apoptosis in multiple cancer
      cell lines while sparing noncancerous cells and cell lines. Here we report the
      ability of PST to induce apoptosis specifically in human breast cancer cell lines
      MCF-7 and Hs-578-T compared to their non cancerous counterparts. In cancer cells
      PST caused increased levels of reactive oxygen species (ROS), decreased ATP and
      mitochondrial membrane permeabilization indicating the activation of the
      mitochondrial pathway of apoptosis. In combination with the anti-estrogen
      Tamoxifen, PST had a synergic effect. Both compounds caused increased production
      of ROS when applied to isolated mitochondria from these cancer cell lines
      supporting the observation that Tamoxifen might work through mechanisms distinct
      from the canonical estrogen receptor antagonism.

PMID- 18075308
TI  - Sensitive and quantitative detection of KRAS2 gene mutations  in pancreatic duct
      juice differentiates patients with pancreatic cancer  from chronic pancreatitis,
      potential for early detection.
AB  - KRAS2 gene mutations are found in 75-90% of infiltrating pancreatic ductal
      adenocarcinomas but can also be present with other nonneoplastic pancreatic
      diseases. We recently developed a novel sensitive assay for point mutation
      detection, called "LigAmp", which can detect one mutant molecule in the presence
      of 10,000 wild-type molecules and can quantify mutant DNA over a wide dynamic
      range. We analyzed KRAS2 mutations in surgically-collected pancreatic duct juice
      samples from patients with pancreatic adenocarcinoma (n = 27) and chronic
      pancreatitis(n = 9). DNA sequencing demonstrated that 17 of the 27 pancreatic
      cancers harbored KRAS2 mutations at codon 12, including G12D (GGT-->GAT), G12V
      (GTT), and G12R (CGT). We determined the relative amounts of each KRAS2 mutant by
      simultaneously quantifying wild-type and mutant KRAS2 DNA. For all pancreatic
      adenocarcinoma patients, the dominant KRAS2 mutation detected in the pancreatic
      juice corresponded to that found in the primary cancer. Mutation levels were
      substantially higher in patients with pancreatic cancer (0.05 to 82% of total
      KRAS2 molecules) compared to those with chronic pancreatitis (0 to 0.7%). Among
      patients with mutant KRAS2 positive cancers, all but one (94%) had mutant KRAS2
      DNA concentrations of more than 0.5% in their pancreatic juice samples, whereas
      only 1 of 9(11%) pancreatic juice samples from patients with chronic pancreatitis
      had more than 0.5% mutant KRAS2 DNA, corresponding to a sensitivity of 94% and a
      specificity of 89%. LigAmp quantification of mutant KRAS2 in pancreatic juice
      differentiates pancreatic adenocarcinoma from chronic pancreatitis, and may be a
      useful early detection tool for pancreatic cancer.

PMID- 18075310
TI  - Prostaglandin E2: making more of your marrow.
AB  - We have recently demonstrated through a chemical screen in the zebrafish embryo
      that prostaglandin E2 (PGE2) is an evolutionarily conserved regulator of
      hematopoietic stem cell (HSC) number. These results have further been confirmed
      by in vitro and in vivo studies in the murine model. Bioactive PGE2 derivatives
      have potential clinical application to accelerate recovery of the hematopoietic
      system following chemotherapy or irradiation. Ex vivo expansion of HSCs prior to
      stem cell transplantation may improve reconstitution of hematopoiesis and immune
      function. This article aims to summarize current knowledge of PGE2-mediated
      regulation of blood cell homeostasis as well as to discuss the proposed use of
      PGE2 to expand hematopoietic stem cells for transplantation in the clinical
      setting.

PMID- 18075309
TI  - Multiple kinases and system robustness: a link between Cdc37 and genome
      integrity.
AB  - We identified 38 genes as having a genetic interaction with a mutant form of the
      kinase specific chaperone, Cdc37, using a genome-wide synthetic screening
      approach. The identified genes included a sub-network of highly interacting genes
      enriched for functions in genome integrity and comprising multiple components of
      several discrete molecular machines. A network analysis approach related these
      machines to a small group of cell cycle checkpoint kinases.

PMID- 18075311
TI  - Revealing a role of microRNAs in the regulation of the biological clock.
AB  - In the last decade numerous studies have unveiled the pervasive role of microRNAs
      (miRNAs), a class of small, non-coding transcripts, in post-transcriptional gene
      regulation in biological processes ranging from development to cancer. Until
      recently, the circadian clock has been modeled as simple, interlocking,
      transcriptional feedback loops that drive rhythmic gene expression of a few core
      'clock' determinants. The biological implications of miRNAs are extended further
      by our recent discovery that miRNAs are expressed in the suprachiasmatic nuclei
      (SCN), the master circadian clock in mammals, in a rhythmic and inducible
      fashion, and modulate the intrinsic pacemaker activity and resetting capacity of
      the SCN. In this review, we will discuss the specific roles of miRNA-(miR-)132
      and miR-219 in the SCN, as well as a more general outlook on this newly
      elucidated layer of circadian clock regulation: inducible translation control via
      miRNAs.

PMID- 18075312
TI  - A Cul3-based E3 ligase regulates mitosis and is required to maintain the spindle
      assembly checkpoint in human cells.
AB  - The spindle assembly checkpoint (SAC) is a mechanism that prevents premature
      chromosome segregation in anaphase before all chromosomes are correctly attached
      to the mitotic spindle. Errors in chromosome segregation lead to aneuploidy,
      which may be causally involved in tumorgenesis. Kinetochore complexes are the
      structural components of the SAC, which are tightly regulated by various
      mechanisms including phosphorylation and ubiquitin-dependent proteolysis. Recent
      studies shed new light on the regulatory pathways of the ubiquitin proteasome
      system involved in SAC signaling. Here we present evidence that a Cul3-based E3
      ubiquitin-ligase is required to maintain SAC signaling in human cells.
      Inactivation of the Cul3/KLHL9/KLHL13 ligase leads to premature degradation of
      Cyclin B and exit from the mitotic state in the presence of microtubule poisons.
      We discuss possible mechanisms how Cul3 may be required to maintain SAC activity
      by ubiquitination of the chromosomal passenger protein Aurora B.

PMID- 18075313
TI  - Multiple mechanisms for p27(Kip1) translocation and degradation.
AB  - The nuclear export and rapid degradation of p27(Kip1) at the G(0)-G(1) transition
      are critical events for effective progression of the cell cycle. Several pathways
      have been proposed at the molecular level for the export of this cyclin-dependent
      kinase inhibitor from the nucleus. However, the addition of each new pathway
      renders the situation more complicated. We recently showed that cyclin D2 links
      growth signals to the cytoplasmic translocation and degradation of p27 at the
      G(0)-G(1) transition. Here we describe our findings and discuss how the multiple
      potential mechanisms for p27 translocation that precedes its degradation might be
      integrated in the context of growth stimulation and G(1) progression.

PMID- 18075314
TI  - Phosphatases, DNA damage checkpoints and checkpoint deactivation.
AB  - Cells have evolved intricate and specialized responses to DNA damage, central to
      which are the DNA damage checkpoints that arrest cell cycle progression and
      facilitate the repair process. Activation of these damage checkpoints relies
      heavily on the activity of Ser/Thr kinases, such as Chk1 and Chk2 (Saccharomyces
      cerevisiae Rad53), which are themselves activated by phosphorylation. Only more
      recently have we begun to understand how cells disengage the checkpoints to
      reenter the cell cycle. Here, we review progress toward understanding the
      functions of phosphatases in checkpoint deactivation in S. cerevisiae, focusing
      on the non-redundant roles of the type 2A phosphatase Pph3 and the PP2C
      phosphatases Ptc2 and Ptc3 in the deactivation of Rad53. We discuss how these
      phosphatases may specifically recognize different phosphorylated forms of Rad53
      and how each may independently regulate different facets of the checkpoint
      response. In conjunction with the independent dephosphorylation of other
      checkpoint proteins, such regulation may allow a more tailored response to DNA
      damage that is coordinated with the repair process, ultimately resulting in the
      resumption of growth.

PMID- 18075315
TI  - The cyclin-dependent kinase inhibitor seliciclib (R-roscovitine; CYC202)
      decreases the expression of mitotic control genes and prevents entry into
      mitosis.
AB  - The cyclin-dependent kinase (CDK) inhibitor seliciclib (R-roscovitine, CYC202)
      shows promising antitumor activity in preclinical models and is currently
      undergoing phase II clinical trials. Inhibition of the CDKs by seliciclib could
      contribute to cell cycle arrest and apoptosis seen with the drug. However, it is
      common for drugs to exert multiple effects on gene expression and biochemical
      pathways. To further our understanding of the molecular pharmacology of
      seliciclib, we employed cDNA microarrays to determine changes in gene expression
      profiles induced by the drug in HT29 human colon cancer cells. Concentrations of
      seliciclib were used that inhibited RB phosphorylation and cell proliferation. An
      increase in the mRNA expression for CJUN and EGR1 was confirmed by Western
      blotting, consistent with activation of the ERK1/2 MAPK pathway by seliciclib.
      Transcripts of key genes required for the progression through mitosis showed
      markedly reduced expression, including Aurora-A/B (AURK-A/B), Polo-like kinase
      (PLK), cyclin B2 (CCNB2), WEE1 and CDC25C. Reduced expression of these mitotic
      genes was also seen at the protein level. siRNA-mediated depletion of Aurora-A
      protein led to an arrest of cells in the G(2)/M phase, consistent with the
      effects of seliciclib treatment. Inhibition of mitotic entry following seliciclib
      treatment was indicated by a reduction of histone H3 phosphorylation, which is
      catalyzed by Aurora-B, and by decreased expression of mitotic markers, including
      phospho-protein phosphatase 1 alpha. The results indicate a potential mechanism
      through which seliciclib prevents entry into mitosis. Gene expression profiling
      has generated hypotheses that led to an increase in our knowledge of the cellular
      effects of seliciclib and could provide potential pharmacodynamic or response
      biomarkers for use in animal models and clinical trials.

PMID- 18075316
TI  - MeCP2 deficiency in the brain decreases BDNF levels by REST/CoREST-mediated
      repression and increases TRKB production.
AB  - Disruptions in the expression of the BDNF gene that encodes a neurotrophic factor
      involved in neuronal survival, differentiation and synaptic plasticity has been
      proposed to contribute to the molecular pathogenesis of Rett syndrome. Rett
      syndrome (RTT) is a neurodevelopmental disorder, caused by mutations in the X
      linked methyl CpG binding protein 2 gene (MeCP2). MeCP2 deficiency in the brain
      has been shown to decrease overall expression of BDNF in spite of an observed
      increase in the activity of promoter III that appears to be controlled directly
      by MeCP2. Therefore, how MeCP2 deficiency causes an overall downregulation of
      BDNF expression was an enigma. Here we report that MeCP2 deficiency in human and
      mouse brain causes an increase in expression of two neuronal gene transcriptional
      repressors REST (RE1 silencing transcription factor), and CoREST. MeCP2 binds to
      and is involved in repression of Rest and CoRest promoters despite their
      unmethylated state. MeCP2 depletion is associated with a change in the histone
      modification profile to a more active conformation. The elevated levels of REST
      and CoREST in the brain of RTT patients and MeCP2 deficient mice result in
      downregulation of BDNF, apparently by their binding to the RE1 (element) located
      between the first two promoters of the BDNF gene. Interestingly, the NTRK2 gene
      that encodes the BDNF receptor, TRKB, was overexpressed in MeCP2 deficient human
      and mouse brains either directly or as an attempt to compensate for BDNF
      deficiency.

PMID- 18075317
TI  - Toward a paucity of poverty.

PMID- 18075318
TI  - Charity. Nurses have always worked to help the poor. Right?

PMID- 18075336
TI  - A fistula clinic repairs lives in Uganda.

PMID- 18075337
TI  - The Governor's Wellmobile program.

PMID- 18075338
TI  - 'We're not poor...' A rural doctor's lens on the Adirondacks.

PMID- 18075340
TI  - How to try this: predicting pressure ulcer risk. Using the Braden scale with
      hospitalized older adults: the evidence supports it.

PMID- 18075342
TI  - How to try this: predicting patient falls. Using the Hendrich II Fall Risk Model
      in clinical practice.

PMID- 18075344
TI  - The Nurse-Family Partnership.

PMID- 18075347
TI  - Colorado nurses and the FFP.

PMID- 18075359
TI  - The Nurse-Family Partnership: a policy priority. In-home nurse visits are cost
      effective and evidence based.

PMID- 18075363
TI  - We aren't in orientation anymore.

PMID- 18075365
TI  - Continuing Medical Education Questions.

PMID- 18075364
TI  - The other cheek.

PMID- 18075366
TI  - Barriers to implementing protocol-based sepsis resuscitation in the emergency
      department--results of a national survey.
AB  - OBJECTIVE: To identify barriers to implementation of a written protocol for early
      goal-directed therapy for severe sepsis in the busiest emergency departments in
      the United States. DESIGN: Telephone survey with both quantitative and
      qualitative analysis. SETTING: Two busiest teaching and two busiest nonteaching
      emergency departments in each of the 25 most densely populated combined
      statistical areas in the United States. SUBJECTS: Twenty-four physician directors
      and 40 nursing managers representing 53% of the 100 emergency departments
      surveyed. INTERVENTIONS: Survey questionnaire. MEASUREMENTS AND MAIN RESULTS:
      Respondents identified lack of available nursing staff to perform the procedure,
      the inability to monitor central venous pressure in the emergency department, and
      challenges in identifying septic patients as the most frequent barriers. Although
      nurse managers and physicians identified similar barriers, nurses were more
      likely than physicians to list central venous catheter insertion as an important
      barrier (38% vs. 5%; p = .01), and physicians were more likely to endorse lack of
      agreement with the early goal-directed therapy resuscitation protocol (16% vs.
      0%; p = .03). There were no statistically significant differences in the rankings
      assigned by clinicians from teaching and nonteaching hospitals. Qualitative
      analysis of open-ended questions identified barriers in a number of areas,
      including barriers to initiating the protocol process and factors that
      distinguish sepsis from other time-sensitive diseases in the emergency
      department. CONCLUSIONS: Nurse managers and physician directors of busy emergency
      departments representing the largest urban areas in the United States identify
      multiple barriers to implementing time-sensitive resuscitation to patients with
      severe sepsis. More than half of all respondents recognized a critical shortage
      of nursing staff, problems in obtaining central venous pressure monitoring, and
      challenges in identification of patients with sepsis as the largest roadblocks to
      overcome in implementing early goal-directed therapy.

PMID- 18075367
TI  - No margin, no mission: R.I.P.

PMID- 18075368
TI  - Biomarkers of cardiac injury in acute respiratory distress syndrome: getting to
      the heart of the matter.

PMID- 18075369
TI  - Weaning the "unweanable": liberating patients from prolonged mechanical
      ventilation.

PMID- 18075370
TI  - Correctly scoring infections: CSI in the ICU.

PMID- 18075371
TI  - Barriers to the optimal resuscitation of patients with severe sepsis? Transfer to
      a level I critical care center!

PMID- 18075372
TI  - Less confusion and greater clarity regarding delirium.

PMID- 18075373
TI  - Expanding the global epidemiology of sepsis.

PMID- 18075374
TI  - High cycling-off criteria during pressure support in chronic obstructive
      pulmonary disease patients: give them time to get their breath back!

PMID- 18075375
TI  - Who's on first?

PMID- 18075376
TI  - Recognizing shock: who cares, and when?

PMID- 18075377
TI  - Sympathetic blockade for pulmonary embolus: novel therapy or novelty?

PMID- 18075378
TI  - Stem cell delivery to the heart: clarifying methodology and mechanism.

PMID- 18075379
TI  - Activated protein C in sepsis: tightening pulmonary endothelial cells?

PMID- 18075380
TI  - Inadequate mechanical ventilation as the first or the second hit in a two-hit
      model: is there any difference in the injurious impact?

PMID- 18075381
TI  - Rare window: functional magnetic resonance imaging and mild traumatic brain
      injury.

PMID- 18075382
TI  - Covering massive burn injuries: integra-ting and interpreting the data.

PMID- 18075383
TI  - Near-fatal pediatric asthma managed with pumpless arteriovenous carbon dioxide
      removal: help at the margin.

PMID- 18075384
TI  - Industry support and sepsis guidelines.

PMID- 18075385
TI  - Industry support and sepsis guidelines.

PMID- 18075386
TI  - Organ donation after cardiac death: A reexamination of healthcare provider
      attitudes.

PMID- 18075387
TI  - Organ donation after cardiac death: a reexamination of healthcare provider
      attitudes.

PMID- 18075388
TI  - Mono versus combination antibiotic therapy: who is right?

PMID- 18075390
TI  - Mono versus combination antibiotic therapy: Who is right?

PMID- 18075389
TI  - Acute lung injury after severe brain injury--a plea for hypothermia?

PMID- 18075391
TI  - The RIFLE criteria: Are the foundations robust?

PMID- 18075392
TI  - The RIFLE criteria: are the foundations robust?

PMID- 18075393
TI  - The Pancreatitis Outcome Prediction (POP) score: how about hematocrit and
      leukopenia?

PMID- 18075394
TI  - Avoiding the cross-talk phenomenon when assessing cardiac output using the
      transpulmonary thermodilution technique via the femoral vein access.

PMID- 18075395
TI  - Avoiding the cross-talk phenomenon when assessing cardiac output using the
      transpulmonary thermodilution technique via the femoral vein access.

PMID- 18075397
TI  - Upcoming Critical Care Meetings.

PMID- 18075396
TI  - The Pancreatitis Outcome Prediction (POP) score: How about hematocrit and
      leukopenia?

PMID- 18075398
TI  - An investigation into the effect of electrode placement of transcutaneous
      electrical nerve stimulation (TENS) on experimentally induced ischemic pain in
      healthy human participants.
AB  - INTRODUCTION: It is claimed that transcutaneous electrical nerve stimulation
      (TENS) operates via a segmental mechanism by reducing ongoing transmission and
      sensitization of nociceptive dorsal horn neurons. Hence, TENS electrodes are
      usually placed at the site of pain. OBJECTIVE: This study compared TENS
      administered at the site of experimentally induced ischemic pain (ipsilateral
      forearm) with TENS administered at a location not related to pain (contralateral
      lower leg). METHODS: Ten healthy, pain free volunteers took part in a cross-over
      study during which ischemic pain was induced in the nondominant arm using a
      modified version of submaximal effort tourniquet technique. Pain intensity was
      taken at 1-minute interval/s for 5 minutes while receiving TENS either at the
      ipsilateral arm or contralateral leg. RESULTS: There were no statistically
      significant differences in pain intensity or McGill Pain Questionnaire ratings
      between TENS given at the arm compared with the leg. DISCUSSION: Taken at face
      value, the findings suggest that TENS effects were nonspecific and that electrode
      location does not affect outcome. However, this study should be seen as a call
      for further research rather than a definitive conclusion.

PMID- 18075399
TI  - Complementary and alternative medicine use for arthritis pain in 2 Chicago
      community areas.
AB  - OBJECTIVE: To compare the use of complementary and alternative medicine (CAM) for
      arthritis between 2 ethnically distinct metropolitan Chicago community areas.
      METHODS: A telephone interview survey of adults age 45 years or above living in
      North (88.9% white) or South (79.7% African American) areas. Of 763 respondents,
      405 reported arthritis or chronic joint symptoms and were asked about use and
      satisfaction with 7 CAM therapies. Differences between areas were compared with
      population-weighted tests; multiple logistic regression was used to analyze the
      likelihood of CAM use controlled for demographics, behavioral risk factors, and
      arthritis severity. RESULTS: South Chicago respondents had a higher prevalence
      and more severe arthritis symptoms such as mean joint pain and more functional
      limitations. Use of CAM therapy by South Chicago respondents, most commonly
      massage and relaxation techniques, was 10% greater than North Chicago respondents
      (61.5% to 51%) but this was not significantly different. Among CAM users, South
      Chicago respondents reported higher satisfaction with 6 of the 7 CAM therapies
      and greater future interest in CAM therapies. Poor overall health status
      (P=0.03), arthritis pain (P=0.005), and concomitant use of prescription
      medications (P=0.03) were the only significant predictors of CAM use. DISCUSSION:
      Although there were only small differences in overall CAM use by area, older
      residents of largely African American communities were enthusiastic users of
      relaxation, massage, and nutritional and dietary techniques. CAM modalities could
      be important adjuncts to traditional medical treatment of arthritis pain for
      minority communities.

PMID- 18075400
TI  - beta-Endorphin modulates adenosine provoked chest pain in men, but not in women-a
      comparison between patients with ischemic heart disease and healthy volunteers.
AB  - INTRODUCTION: Increasing evidence suggests the existence of sex differences in
      pain perception. Adenosine, an early messenger for myocardial ischemia induces
      angina pectorislike symptoms in healthy volunteers and in patients with ischemic
      heart disease. AIMS: To study whether sex influences adenosine-provoked chest
      pain and the analgesic effect of the opioid receptor agonist beta-endorphin.
      MATERIALS AND METHODS: Twenty patients (10 male and 10 female) with significant
      coronary artery disease and 20 healthy volunteers (10 male and 10 female) were
      studied. Both the hand algometer and Borg CR-10 scale were used to estimate chest
      pain. Chest pain was provoked double-blind by injections of placebo, 1/3, 2/3,
      3/3 of maximal tolerable dose of adenosine twice in randomized order. This
      procedure was repeated after bolus injection of beta-endorphin followed by
      infusion and repeated a third time after bolus injection of naloxone 0.8 mg.
      Central chest pain and physiologic responses were quantified using hemodynamic
      and psychophysical methods. RESULTS: Pain estimate by hand algometer and the Borg
      CR-10 scale was correlated (r=0.77, P<0.001). Both sexes reported a dose
      dependent increase of adenosine-provoked chest pain with no differences for
      maximum tolerable dose of adenosine per kilogram. beta-Endorphin administration
      lowered adenosine-provoked pain in both male patients and male healthy volunteers
      (P=0.02) but not in women. Naloxone tended to increase the pain perception in
      male patients (P=0.052) and male healthy volunteers (P=0.054), but did not have
      any significant effect on pain modalities in female. CONCLUSIONS: In conclusion,
      women were resistant to beta-endorphin modulation of adenosine-provoked chest
      pain. In male patients, beta-endorphin induced analgesia.

PMID- 18075401
TI  - Effect of eutectic mixture of local anesthetics (EMLA) for pain relief during
      suprapubic aspiration in young infants: a randomized, controlled trial.
AB  - OBJECTIVES: The purpose of this study was to determine whether a eutectic mixture
      of local anesthetics (EMLA) cream reduce the pain experienced by newborns and
      young infants undergoing suprapubic aspiration (SPA). METHODS: A single-center,
      randomized, placebo-controlled, double-blind, prospective study including 52
      infants 1 to 60 days of age undergoing SPA to obtain urine for culture. Twenty
      four infants were randomly assigned to receive 1-g EMLA cream 1 hour before the
      procedure, whereas 28 were randomly assigned to receive placebo cream 1 hour
      before the planned procedure. Pain symptoms were measured using the Premature
      Infant Pain Profile (PIPP). RESULTS: The mean PIPP scores were significantly
      lower in the EMLA group compared with the placebo group (8.90+/-3.04 vs. 10.46+/
      2.29; P=0.038). There were significantly fewer patients in the EMLA group who
      were scored as having some degree of pain (defined as PIPP score >6) in
      comparison with the placebo group (70% vs. 96%; P=0.025). DISCUSSION: Newborns
      and infants undergoing SPA experience pain during the procedure. Application of
      EMLA cream 1 hour before SPA is effective in reducing the pain associated with
      SPA. In situations in which an SPA is not emergent, strong consideration should
      be given to the use of EMLA.

PMID- 18075402
TI  - Interrater reliability of algometry in measuring pressure pain thresholds in
      healthy humans, using multiple raters.
AB  - OBJECTIVE: To evaluate interrater reliability using 5 newly trained observers in
      the assessment of pressure pain threshold (PPT) using a fixed-angle algometer.
      METHODS: The study design comprised 2 phases. Phase 1: 5 undergraduate physical
      therapists were trained in algometry at a predefined angle, at a rate of 5
      Newtons (N)/s, to the first dorsal interosseous muscle. Each observer then
      underwent a competency test of the application speed. The aim was to achieve
      repeated applications at 5 N/s without visual feedback from the algometer. Phase
      2: the 5 observers measured PPT of 13 healthy volunteers, at the first dorsal
      interosseous muscle. The sequence of observer measurements for each participant
      was randomized. Mean PPT values for each observer were analyzed using repeated
      measures analysis of variance, intraclass correlation coefficient (ICC2,1), and
      standard error of measurement, with 95% confidence intervals (CIs). RESULTS: No
      significant differences between observers' mean values were found (P=0.094),
      suggesting no bias. The ICC was 0.91 (95% CI 0.82, 0.97). The standard error of
      measurement value was 6.27 N/cm (95% CI 5.35, 7.59). Differences in PPT
      measurements of more than 17.39 N/cm (1.77 kg/cm) are likely to exceed the
      magnitude of measurement error, and could be used to indicate true change. This
      margin of error is, however, somewhat larger than a previously proposed minimum
      clinically important difference in PPT of 14.71 N/cm (1.5 kg/cm). DISCUSSION:
      This study provides new evidence that trained observers can apply an algometer at
      a consistent rate and provide highly reliable measures of PPT in healthy humans,
      when PPT is calculated as the mean of 3 trials.

PMID- 18075403
TI  - Unipedicular vertebroplasty for osteoporotic compression fracture using an
      individualized needle insertion angle.
AB  - OBJECTIVES: In the classic transpedicular vertebroplasty, second needle placement
      is routinely required at the same level. However, each patient requires a
      different needle insertion angle (NIA) at each site. Therefore, precise NIA is
      required for each fractured vertebral body. In this study, we performed a
      unipedicular approach through an individualized NIA that had been evaluated with
      axial magnetic resonance imaging before vertebroplasty. METHODS: We performed
      percutaneous vertebroplasty (PVP) on 103 vertebrae in 63 consecutive patients (50
      women, 13 men; mean age, 70.4 y; range, 56 to 87 y). Before PVP, we measured the
      NIA for each pedicle. If leakage occurred without midline cement crossover, the
      unipedicular approach was stopped and changed to a bipedicular approach. RESULTS:
      PVPs were performed from T7 to L5. We considered a successful outcome of a
      unipedicular approach to be when the center of vertebral body was filled with
      cement. Successful unipedicular PVPs were performed in 93 (90.3%) of 103 cases.
      Fifty-six of 63 patients were included for the pain evaluation. There was a
      statistically significant difference (P<0.0001) between pre-visual analog scale
      (VAS) (84) and post-VAS (postoperatively at 1 d-VAS: 32, postoperatively at 1 mo
      VAS: 34, and postoperatively at 3 mo-VAS: 37). No statistically significant
      difference was found between pre-NIAs and post-NIAs. A positive correlation was
      found between pre-NIAs and post-NIAs. DISCUSSION: Unipedicular PVP can be
      performed safely, provided the operator has a thorough knowledge of the bony
      landmarks and the anatomy of the pedicle. A unipedicular approach could be
      considered first using individualized NIA at each vertebral level.

PMID- 18075404
TI  - Psychometric properties of the Doloplus-2 observational pain assessment scale and
      comparison to self-assessment in hospitalized elderly.
AB  - OBJECTIVES: Self-report is the "gold standard" for pain assessment, however,
      observational pain scales, such as Doloplus-2 must be used for patients who
      cannot communicate. In this follow-up study, we report the psychometric
      properties of the observational Doloplus-2 scale using the visual analog scale
      (VAS) pain score as a gold standard and evaluate its performance. METHOD:
      Prospective clinical study of 180 hospitalized older patients who demonstrated
      good comprehension and reliable use of the VAS: 131 participants with dementia
      and 49 without. All participants assessed their chronic pain using the VAS.
      Doloplus-2 was independently completed by the nursing team. RESULTS: Mean age of
      patients (133 women, 47 men) was 83.7+/-6.5. Median mini-mental state examination
      of patients with diagnosis of dementia was 18.0+/-7.7. Nearly half of the
      patients (49%) reported that they experienced pain in response to a direct
      question. The administration of Doloplus-2 was possible in all 180 patients.
      Doloplus-2 correlated moderately with self-assessment (Spearman coefficient:
      0.46). In a multiple regression model, Doloplus-2 predicted 41% of the
      variability in pain intensity measured by VAS. The somatic dimension alone
      explained 36% of the variance, the psychosocial bloc 5% with no better
      contribution of the psychomotor bloc. To shorten Doloplus-2, we constructed a
      version with only the 5 items that were significantly associated with the VAS
      score in the multiple regression models. DISCUSSION: The observational Doloplus-2
      scale correlates moderately with self-assessment pain score and has adequate
      internal consistency. Our data also suggest that Doloplus-2 could be
      substantially shortened as the brief version performed similarly to the complete
      Doloplus-2.

PMID- 18075405
TI  - Spinal canal size and clinical symptoms among persons diagnosed with lumbar
      spinal stenosis.
AB  - OBJECTIVE: Clinical symptoms associated with lumbar spinal stenosis (LSS) are
      believed to be due to neurogenic claudication caused by narrowing of the central
      and lateral spinal canals. However, there is a paucity of published data on these
      relationships. The purpose of the present study was to examine the relationship
      between clinical symptoms associated with LSS and osseous anterior-posterior (AP)
      spinal canal diameter as measured on axial magnetic resonance imaging. DESIGN:
      Cross-sectional study conducted at a University Spine Program. Fifty persons with
      a clinical diagnosis of LSS were administered measures of clinical pain and
      perceived function. Walking distance in the laboratory and community was also
      assessed. Participants also underwent magnetic resonance imaging of the spine.
      RESULTS: Using recommended upper limits from the literature, patients with
      smaller canals reported greater perceived disability, but no other group
      differences emerged. In the entire sample, AP spinal canal diameter was not
      significantly associated with any of the clinical symptom measures examined. Body
      mass index was found to be significantly related to walking distance, but not
      perceived function or pain. CONCLUSIONS: AP spinal canal diameter is not
      predictive of clinical symptoms associated with LSS. The findings also suggest
      that body mass may play a significant role in functional limitations observed in
      this population.

PMID- 18075406
TI  - The local and referred pain from myofascial trigger points in the temporalis
      muscle contributes to pain profile in chronic tension-type headache.
AB  - OBJECTIVE: To assess the local and referred pain areas and pain characteristics
      evoked from temporalis muscle trigger points (TrPs) in chronic tension-type
      headache (CTTH). METHODS: Thirty CTTH patients and 30 age and sex-matched
      controls were studied. A headache diary was kept for 4 weeks to substantiate the
      diagnosis and record the pain history. Both temporalis muscles were examined for
      the presence of myofascial TrPs in a blinded fashion. The local and referred pain
      intensities, referred pain pattern, and pressure pain threshold were recorded.
      RESULTS: Referred pain was evoked in 87% and 54% on the dominant and nondominant
      sides in CTTH patients, which was significantly higher (P<0.001) than in controls
      (10% vs. 17%, respectively). Referred pain spread to the temple ipsilateral to
      the stimulated muscle in both patients and controls, with additional referral
      behind the eyes in most patients, but none in controls. CTTH patients reported a
      higher local [visual analog scale (VAS): 5.6+/-1.2 right side, 5.3+/-1.4 left
      side] and referred pain (VAS: 4.7+/-2 right side, 3.5+/-2.8 left side) intensity
      than healthy controls (VAS: 0.8+/-0.7 right side, 0.7+/-0.7 left side for local
      pain; and 0.3+/-0.2 right side, 0.4+/-0.3 left side for referred pain) in both
      temporalis muscles (both, P<0.001). The local and referred pain areas were larger
      in patients than in controls (P<0.001). Twenty-three out of 30 CTTH patients
      (77%) had active TrPs in the temporalis muscle leading to their usual headache
      (17 patients on the right side; 12 on the left side, whereas 6 with bilateral
      active TrPs). CTTH patients with active TrPs in either right or left temporalis
      muscle showed longer headache duration than those with latent TrPs (P=0.004).
      CTTH patients showed significantly (P<0.001) lower pressure pain threshold (1.1+/
      0.2 right side, 1.2+/-0.3 left side) as compared with controls (2.5+/-0.5 right
      side, 2.6+/-0.4 left side). CONCLUSIONS: In CTTH patients, the evoked local and
      referred pain from active TrPs in the temporalis muscle and its sensory
      characteristics shared similar patterns as their habitual headache pain. Local
      and referred pain from active TrPs in the temporalis muscles may constitute one
      of the sources contributing to the pain profile of CTTH.

PMID- 18075407
TI  - Intrathecal treatment in cancer patients unresponsive to multiple trials of
      systemic opioids.
AB  - The aim of this study was to evaluate the clinical response to a combination of
      intrathecal morphine and levobupivacaine in advanced cancer patients who were
      highly opioid-tolerant, being previously treated with multiple opioid trials
      unsuccessfully. Initial intrathecal morphine dose was calculated from the
      previous opioid consumption using a morphine oral-intrathecal ratio of 100:1.
      Then, doses of both drugs were modified during the treatment according to the
      clinical needs and balanced with adverse effects. Fifty-five patients were
      assessed during admission, before starting the intrathecal treatment, during the
      titration phase, and followed up to death, by frequent phone contacts or visits,
      as available. Pain and symptom intensities were recorded before starting the
      intrathecal treatment (T0), at time of hospital discharge (T dis), and then at 1
      month (T1), 3 months (T3), 6 months (T6) intervals, and the last observation, at
      least 1 week before death (T death). Fifty-five patients were selected for
      starting an intrathecal treatment. Thirty-two patients were males. The mean age
      was 60 years (95% CI 57-63), and 65.4% of patients were under 65 years. The most
      frequent indication was the presence of adverse effects and poor pain control.
      Complete data with adequate follow-up until death were available in 45 patients.
      Statistical differences in pain intensity were found at the different time
      intervals examined until death. Statistical decreases in the intensity of
      drowsiness and confusion were found until 1 month after starting intrathecal
      therapy. Statistical differences were found in daily intrathecal morphine doses,
      with a 3-fold increase at time of hospital discharge. Subsequently, further
      increases in doses were not significant. Conversely, systemic opioids, expressed
      as oral morphine equivalents, significantly decreased at all the intervals
      examined until death. Early complications included mild bleeding in 2 patients,
      without consequences, headache in 4 patients, bladder catheterization in 6
      patients, reoperation for bleeding or changes of catheter position in 4 patients,
      unrelated death in 1 patient, and stroke in another 1. Late complications
      included local infection in 2 patients, and discontinuation of intrathecal
      therapy due to spinal compression. In patients who had received multiple trial of
      opioids and routes of administration, the intrathecal treatment started with an
      oral-intrathecal morphine conversion ratio of 100:1, and local anesthetics at the
      most convenient clinical doses provided a long-term improvement of analgesia,
      with a decrease in adverse effects and opioid consumption until death.

PMID- 18075408
TI  - Physician attitudes toward opioid prescribing for patients with persistent
      noncancer pain.
AB  - OBJECTIVES: Physicians frequently express dissatisfaction about caring for
      patients with chronic pain and frequently report that inadequate training and
      concern about addiction are impediments to prescribing opioids. Elderly patients
      with chronic pain may be at increased risk of experiencing uncontrolled pain and
      this patient population is increasingly being cared for by geriatricians rather
      than internists. We sought to determine if there is a differential impact on
      internists and geriatricians of the factors that adversely affect attitudes
      toward opioid prescribing. METHODS: Anonymous survey of geriatric and internal
      medicine physicians at a large urban academic medical center about their beliefs
      and behaviors regarding opioid prescribing. RESULTS: One hundred thirty-two of
      187 physicians completed the survey for an overall response rate of 71%.
      Controlling for level of training, internists were more likely to be concerned
      about illegal diversion (adjusted odds ratio=10.0, P=0.004), were more concerned
      about causing addiction (38% vs. 0%, P<0.001), and were more likely to be
      concerned about their inability to prescribe the correct opioid dose (adjusted
      odds ratio=11.1, P=0.020). DISCUSSION: Factors shown to have an adverse affect on
      opioid prescribing disproportionately impact on the attitudes of internists
      compared with geriatricians. Further research is needed to determine if there is
      also a differential impact on how internists care for their elderly patients with
      chronic pain.

PMID- 18075409
TI  - Evaluation of a standardized internet-based and telephone-based patient
      monitoring system for pain therapy with transdermal fentanyl.
AB  - The aim of the present observational 4-week study was to document the feasibility
      and utility of telephone-based or Internet-based pain monitoring in patients with
      chronic cancer or noncancer pain, such as nociceptive or neuropathic pain, using
      transdermal fentanyl. Pain intensity, treatment tolerability, activities of daily
      living, quality of life, and patient and physician satisfaction were evaluated in
      60 (60% women, 42% opioid-naive) chronic pain patients who were switched from
      oral pain therapy to transdermal fentanyl therapy because of persisting severe
      pain. When the total dataset of all patient entries was analyzed, treatment with
      transdermal fentanyl led to decreases in maximal and mean pain scores as reported
      by the patients (-14% and -19%, respectively, last observation carried forward
      vs. baseline). Pain reduction was more pronounced in opioid-naive than in opioid
      experienced patients (-35% and -25% vs. baseline, respectively; P=0.03). Overall,
      impairment of daily activities was reduced by 23% with transdermal fentanyl. No
      effect was observed with regard to quality of life and use of rescue pain
      medication. Transdermal fentanyl was generally well tolerated. Most patients
      (60%) preferred the telephone-based to the Internet-based or Internet combined
      with telephone questionnaires. Patient preference was driven by age, whereby
      younger patients tended to prefer the Internet and older patients the telephone
      (mean age, 45 and 54 y, respectively; difference n.s.). Internet-based and
      telephone-based monitoring of the efficacy and tolerability of opioid treatment
      for chronic pain was feasible in daily practice and generally well accepted by
      patients and physicians. Future research will determine the relative contribution
      of these 2 new options for patient-physician interaction and delineate their role
      in improving chronic pain control.

PMID- 18075411
TI  - The laparoscopic approach to control intractable pelvic neuralgia: from
      laparoscopic pelvic neurosurgery to the LION procedure.
AB  - OBJECTIVE: To present different aspects and advantages of the laparoscopic
      approach to the pelvic nerves aimed at treating intractable pelvic neuralgia.
      METHODS: We report on a nonconsecutive series of 7 patients with different types
      and etiologies of chronic pelvic neuralgia, all of whom underwent laparoscopy. In
      all 7 cases, the neuralgia was refractory to medical management and had profound
      socioeconomic consequences for the patients. RESULTS: Techniques of laparoscopic
      transperitoneal neurolysis of several pelvic somatic nerves are described but
      also our technique of laparoscopic implantation of neuroprothesis for
      neuromodulation on somatic pelvic nerves or on autonomic pelvic nerves as the
      superior hypogastric plexus. DISCUSSION: Laparoscopic approach to the pelvic
      nerves opens new possibilities for the diagnosis and treatment of pelvic
      neuralgia, and offers new curative surgical techniques.

PMID- 18075412
TI  - Radiation-induced alarm and failure of an implanted programmable intrathecal
      pump.
AB  - Numerous potential complications are associated with the use of programmable
      intrathecal (IT) drug delivery systems. Radiation is often assumed to cause
      dysfunctions of the programmable IT device. However, radiation-induced failure of
      this device and limits of dose exposure have not clinically documented. Here we
      reported an alarm and failure of an implanted programmable IT pump in a turn-off
      status exposed directly to radiation used for treatment of a retroperitoneal
      sarcoma. The radiation-induced alarm was likely secondary to the electronic
      circuit damage and/or battery depletion. Estimated cumulative doses to the pump
      were in the range of 28.5 to 36 Gy when the alarm occurred after 20 daily
      treatments. The IT pump itself exposed to this high-dose radiation did not pose
      any risk to the patient or the environment. This is the first case description
      about the pump malfunction secondary to clinical radiotherapy, which is very
      useful to physicians who manage the pain and radiotherapy for cancer patients.

PMID- 18075410
TI  - Objective and subjective assessment of sleep in adolescents with chronic pain
      compared to healthy adolescents.
AB  - OBJECTIVES: The purpose of this study was to compare sleep of adolescents with
      chronic pain and healthy adolescents using both subjective and objective sleep
      assessments, and to identify correlates of poor sleep. METHODS: Forty adolescents
      (n=20 with chronic pain and n=20 healthy adolescents), aged 12 to 17 years (72.5%
      female) participated. Adolescents completed self-report measures of pain, sleep
      quality and hygiene, presleep arousal/worry, and depressive symptoms. Sleep
      patterns were assessed over 7 consecutive days using an actigraph, a motion
      monitoring device detecting sleep-wake patterns by measuring activity levels.
      Total sleep time, sleep efficiency, wake time, and wake bouts were derived from
      the actigraph and aggregated for analysis. RESULTS: Compared with healthy peers,
      adolescents with chronic pain demonstrated similar total sleep time as healthy
      adolescents, but significantly poorer sleep. In particular, adolescents with
      chronic pain subjectively reported poorer sleep quality and increased insomnia
      symptoms, and demonstrated lower actigraphic sleep efficiency and more wake bouts
      compared with their healthy peers. Depressive symptoms and worry at bedtime were
      significant predictors of subjectively reported sleep quality but not of
      actigraphic sleep. DISCUSSION: Adolescents with chronic pain evidenced poorer
      sleep quality, increased insomnia symptoms, and less efficient sleep with more
      wake bouts in comparison with healthy adolescents, findings that require
      replication in a larger sample. Assessment and management of sleep disturbances
      is an important aspect of care for children and adolescents with chronic pain.

PMID- 18075413
TI  - Effective surgical relief of complex regional pain syndrome (CRPS) using a PGA
      collagen nerve guide tube, with successful weaning from spinal cord stimulation.

PMID- 18075414
TI  - Reliability of bone scintigraphy for suspected scaphoid fractures.
AB  - PURPOSE: To examine the observer variation for bone scintigraphy in the detection
      of occult scaphoid fractures in daily practice, using only the early bone
      scanning images. METHODS: One hundred bone scans of patients with a suspected
      scaphoid fracture but negative initial radiographs were prospectively included to
      calculate the inter- and intraobserver variation. Three nuclear medicine
      physicians independently evaluated all bone scans at 2 different points in time
      with a 3-month interval. The observers filled out a blinded scoring sheet for
      each patient. They scored if a scaphoid fracture was present or not. In addition,
      they scored the presence or absence of another fracture. The inter- and
      intraobserver variation was analyzed using the kappa statistic. RESULTS: The
      interobserver variation showed substantial agreement for a scaphoid fracture and
      almost perfect agreement for another fracture. The intraobserver variation showed
      almost perfect agreement for both a scaphoid fracture and another fracture.
      CONCLUSIONS: In the present study, early static images of bone scintigraphy for
      suspected scaphoid fractures showed very little inter- and intraobserver
      variation. In addition, expertise does not seem to have a negative influence on
      the results. This enhances the possibility of using bone scintigraphy in daily
      practice.

PMID- 18075415
TI  - Assessment of intra-arterial injected autologous bone marrow mononuclear cell
      distribution by radioactive labeling in acute ischemic stroke.
AB  - OBJECTIVE: To evaluate the feasibility of monitoring the autologous mononuclear
      bone marrow (ABMMN) cells implanted into the brain after acute ischemic stroke by
      the technique of labeling with Tc-99m-HMPAO. CASE REPORT: A 37-year-old man
      presented with aphasia, right-side hypoesthesia, and right homonymous hemianopsia
      after an acute ischemic stroke of the left middle cerebral artery. He was
      included in an autologous bone marrow mononuclear cell-based therapy research
      protocol about the safety of intra-arterial autologous bone marrow mononuclear
      cell transplantation for acute ischemic stroke. Nine days after the stroke he
      received 3.0 x 10(7) ABMMN cells delivered into the left cerebral middle artery
      via a balloon catheter. Approximately 1% of these cells were labeled with 150 MBq
      (4 mCi) Tc-99m by incubation with hexamethylpropylene amine oxime (HMPAO).
      RESULTS: Brain perfusion images with Tc-99m ECD demonstrated hypoperfusion in the
      left temporal and parietal regions. The perfusion brain images were compared with
      tomographic views of the brain obtained 8 hours after ABMMN-labeled cell
      delivery, revealing intense accumulation of the ABMMN-labeled cells in the
      ipsilateral hemisphere. A whole-body scan was done and showed left brain, liver,
      and spleen uptake. CONCLUSIONS: Our results showed that Tc-99m HMPAO can be used
      to label ABMMN cells for in vivo cell visualization, and that brain SPECT imaging
      with labeled ABMMN cells is a feasible noninvasive method for studying the fate
      of transplanted cells in vivo. Additionally, our findings demonstrate the
      localization of these intra-arterially injected cells.

PMID- 18075416
TI  - Sickle cell disease with regional silent cerebral infarction detected by SPECT.
AB  - An 18-year-old boy was admitted to the hospital for a right leg ulcer, which
      appeared 1 year ago. After physical and hematologic examinations, he was referred
      for neurologic and cardiologic examination because his hemoglobin analysis and
      hematologic findings were interpreted as being consistent with sickle cell
      anemia. Although he had no neurologic symptoms, MRI and Tc-99m ethyl cysteinate
      dimer cerebral perfusion single photon emission computer tomography were
      performed to rule out a silent cerebral infarction. Changes secondary to an
      infarct were seen in the region of the caudate nucleus.

PMID- 18075417
TI  - The clinical value of Tc-99m TRODAT-1 SPECT for evaluating disease severity in
      young patients with symptomatic and asymptomatic Wilson disease.
AB  - PURPOSE: The purpose of this study was to determine the clinical value of
      applying Tc-99m TRODAT-1 single photon emission computed tomography (SPECT) of
      the dopamine transporter to evaluate disease severity in young patients with
      symptomatic or asymptomatic Wilson disease (WD). MATERIALS AND METHODS: The
      evaluation of Tc-99m TRODAT-1 SPECT was performed in 18 patients with symptomatic
      WD, 13 patients with asymptomatic WD, and, as controls, 12 normal volunteers
      matched for age and gender. The neurologic symptoms of symptomatic patients were
      evaluated by an experienced neurologist. The ratios of specific striatal Tc-99m
      TRODAT-1 binding [with the cerebellum (CB) as the reference region] were
      calculated as striatum (ST)/CB and compared among the 3 groups. Using correlation
      analysis, the ratios for the WD patients were compared with clinical data on the
      severity of neurologic symptoms. RESULTS: Significant differences of ST/CB ratios
      were found among the 3 groups (Sym vs. Nor, P = 0.000; Asym vs. Nor, P = 0.036;
      Sym vs. Asym, P = 0.011, respectively). In 23 patients (18 with symptomatic WD, 5
      with asymptomatic WD), the posterior putamina showed more remarkable deformation
      and decreased radiotracer uptake. The ST/CB ratios correlated negatively with the
      severity of neurologic symptoms (r = -0.80, P < 0.01). CONCLUSIONS: The decreased
      striatal Tc-99m TRODAT-1 uptake found in young WD patients, including symptomatic
      WD and some asymptomatic WD, as detected with SPECT, seems to indicate
      presynaptic damage of the dopaminergic nerve terminals. The decrease in
      radiotracer uptake was more prominent in the posterior putamina than in the
      caudate heads. The Tc-99m TRODAT-1 SPECT method can be used effectively for
      evaluating disease severity in WD.

PMID- 18075418
TI  - Is early bladder activity in radionuclide cisternography an indirect sign of
      spontaneous intracranial hypotension or sequence of lumbar puncture?
AB  - Spontaneous intracranial hypotension (SIH) is characterized by severe postural
      headache and low cerebrospinal fluid (CSF) pressure. Radionuclide cisternography
      (RC) is of some value in diagnosing CSF leakage causing SIH. However, the
      sensitivity of RC is too low to demonstrate the site of leakage. In these cases,
      the early appearance of the radioactivity in the urinary bladder has also been
      used as an indirect finding in the diagnosis of SIH. The aim of this study was to
      evaluate the diagnostic reliability of early urinary bladder activity as an
      indirect sign of SIH. We investigated early bladder activity in 21 patients with
      suspicion of normal pressure hydrocephalus. Of the 21 subjects, 13 (62%) showed
      early bladder activity. We demonstrated that early bladder activity is observed
      in patients without CSF leakage such as normal pressure hydrocephalus. Therefore,
      this indirect finding of RC is not a reliable finding in diagnosing SIH.

PMID- 18075419
TI  - Correlative imaging in crowned dens syndrome.

PMID- 18075420
TI  - Prostate cancer metastases to shoulder arthroplasty: bone scintigraphy.

PMID- 18075421
TI  - FDG PET/CT for biopsy guidance in Erdheim-Chester disease.

PMID- 18075422
TI  - Paget disease involving the left third metacarpal.

PMID- 18075423
TI  - Primitive neuroectodermal tumor with multiple marrow metastases at presentation.

PMID- 18075424
TI  - Submandibular gland carcinoma with unusual widespread bone marrow metastases
      detected by Tc-99m MDP bone scan and FDG PET.

PMID- 18075425
TI  - Attention deficiency hyperactivity disorder and sphenoid bone fibrous dysplasia
      association in a boy: SPECT/SPECT fusion imaging.

PMID- 18075426
TI  - Incidental finding of prostate cancer and adenomatous colon polyp in a patient
      with lung cancer.

PMID- 18075427
TI  - Delayed epiphyseal closure in a patient with beta-thalassemia major complicated
      by hypogonadotrophic hypogonadism.

PMID- 18075428
TI  - Extramedullary hematopoiesis on F-18 FDG PET/CT in a patient with metastatic
      colon carcinoma.

PMID- 18075429
TI  - Lymphadenopathy due to amyloidosis secondary to Sjogren syndrome and systemic
      lupus erythematosus detected by F-18 FDG PET.

PMID- 18075430
TI  - Urinary leak after renal transplantation proven by SPECT-CT imaging.

PMID- 18075431
TI  - Can I-123-FP-CIT images give us a clue that implies a vascular parkinsonism?

PMID- 18075432
TI  - Usefulness of Tc-99m PMT hepatobiliary scintigraphy in preoperative evaluation of
      flow of biliary drainage in a patient with a biliary-gastric fistula.

PMID- 18075433
TI  - F-18 FDG PET/CT illustrating tumor invasion in the IVC from adrenocortical
      carcinoma.

PMID- 18075434
TI  - FDG PET/CT detection of a gossypiboma in the neck.

PMID- 18075435
TI  - Cutaneous malignant melanoma showing extraosseous accumulation of Tc-99m MDP in a
      metastatic inguinal lymph node on bone scintigraphy.

PMID- 18075436
TI  - FDG PET/CT findings of epithelioid sarcoma in a pediatric patient.

PMID- 18075437
TI  - Current readings in nuclear medicine.

PMID- 18075439
TI  - Evaluating the underlying factors behind variable rate debt.
AB  - BACKGROUND: Recent trends show a greater usage of variable rate debt among health
      care bond issues. In 2004, 63.4% of the total health care bonds issued were
      variable rate compared with 30.6% in 1995 (Fitch Ratings, 2005). PURPOSE: The
      purpose of this study is to gain a better understanding of the underlying
      factors, credit spread, issue characteristics, and issuer factors behind why
      hospitals and health system borrowers select variable rate debt compared with
      fixed rate debt. METHODOLOGY: From 2000 to 2004, this study sampled 230 newly
      issued tax-exempt bonds issued by acute care hospitals and health care systems
      that included both variable and fixed rate debt issues. Using a logistic
      regression model, hospitals with variable rate debt issues were assigned a value
      of 1, whereas hospitals with fixed rate debt issues were assigned a value of 0.
      FINDINGS: This study found a positive association between bond insurance and
      variable rate debt and a negative association between callable feature and
      variable rate debt. Facilities located in certificate-of-need states that
      possessed higher case mix acuity, earned higher profit margins, generated higher
      debt service coverage, and held less debt were more likely to issue variable rate
      debt. PRACTICE IMPLICATIONS: Overall, hospital managers and board members of
      hospitals possessing a strong financial performance have an interest in utilizing
      variable rate debt to lower their cost of capital. In addition, this outcome may
      also reflect that investment bankers are doing a better job in educating senior
      hospital management about the interest rate savings benefit of variable rate
      compared with fixed rate debt.

PMID- 18075440
TI  - Transformational change in health care systems: an organizational model.
AB  - BACKGROUND: The Institute of Medicine's 2001 report Crossing the Quality Chasm
      argued for fundamental redesign of the U.S. health care system. Six years later,
      many health care organizations have embraced the report's goals, but few have
      succeeded in making the substantial transformations needed to achieve those aims.
      PURPOSES: This article offers a model for moving organizations from short-term,
      isolated performance improvements to sustained, reliable, organization-wide, and
      evidence-based improvements in patient care. METHODOLOGY: Longitudinal
      comparative case studies were conducted in 12 health care systems using a mixed
      methods evaluation design based on semistructured interviews and document review.
      Participating health care systems included seven systems funded through the
      Robert Wood Johnson Foundation's Pursuing Perfection Program and five systems
      with long-standing commitments to improvement and high-quality care. FINDINGS:
      Five interactive elements appear critical to successful transformation of patient
      care: (1) Impetus to transform; (2) Leadership commitment to quality; (3)
      Improvement initiatives that actively engage staff in meaningful problem solving;
      (4) Alignment to achieve consistency of organization goals with resource
      allocation and actions at all levels of the organization; and (5) Integration to
      bridge traditional intra-organizational boundaries among individual components.
      These elements drive change by affecting the components of the complex health
      care organization in which they operate: (1) Mission, vision, and strategies that
      set its direction and priorities; (2) Culture that reflects its informal values
      and norms; (3) Operational functions and processes that embody the work done in
      patient care; and (4) Infrastructure such as information technology and human
      resources that support the delivery of patient care. Transformation occurs over
      time with iterative changes being sustained and spread across the organization.
      PRACTICE IMPLICATIONS: The conceptual model holds promise for guiding health care
      organizations in their efforts to pursue the Institute of Medicine aims of
      fundamental system redesign to achieve dramatically improved patient care.

PMID- 18075441
TI  - Country of origin and racio-ethnicity: are there differences in perceived
      organizational cultural competency and job satisfaction among nursing assistants
      in long-term care?
AB  - BACKGROUND: Long-term care facilities nationwide are finding it difficult to
      train and retain sufficient numbers of nursing assistants, resulting in a dire
      staffing situation. Researchers, managers, and practitioners alike have been
      trying to determine the correlates of job satisfaction to address this
      increasingly untenable situation. One factor that has received little empirical
      attention in the long-term care literature is cultural competence. Cultural
      competence is defined as a set of skills, attitudes, behaviors, and policies that
      enable organizations and staff to work effectively in cross-cultural situations.
      PURPOSE: To examine organizational cultural competence as perceived by nursing
      assistants and determine if this was related to differences in job satisfaction
      across countries of origin and racio-ethnic groups. METHODS: Primary data
      collected from a cross-section of 135 nursing assistants at four New England
      nursing homes. Demographics, perceptions of organizational cultural competence,
      and ratings of job satisfaction were collected. A multivariate, generalized
      linear model was used to assess predictors of job satisfaction. A secondary
      analysis was then conducted to identify the most important components of
      organizational cultural competency. RESULTS: Perception of organizational
      cultural competence (p = .0005) and autonomy (p = .001) were the strongest
      predictors of job satisfaction among nursing assistants; as these increase, job
      satisfaction also increases. Neither country of origin nor racio-ethnicity was
      associated with job satisfaction, but racio-ethnicity was associated with
      perceived organizational cultural competence (p = .05). A comfortable work
      environment for employees of different races/cultures emerged as the strongest
      organizational cultural competency factor (p = .04). RECOMMENDATIONS: Developing
      and maintaining organizational cultural competency and employee autonomy are
      important managerial strategies for increasing job satisfaction and improving
      staff retention. Toward this end, creating a comfortable work environment for
      employees of different races/cultures is an integral part of the process.
      Managerial recommendations are discussed.

PMID- 18075442
TI  - Learning from preventable adverse events in health care organizations:
      development of a multilevel model of learning and propositions.
AB  - BACKGROUND: Preventable adverse events represent learning opportunities. Indeed,
      understanding and learning from preventable adverse events are the new
      organizational imperatives in health care. However, health services researchers
      note that there is a dearth of research on learning from failure in health care
      and, in industry, a limited capacity to learn from incidents and failure.
      PURPOSE: We address the gap between awareness of preventable adverse events and
      knowledge that relates to how to respond to them effectively. We develop a
      multilevel model of learning and theorize factors that influence learning from
      preventable adverse events. METHODOLOGY: Drawing upon theories of organizational
      learning and organizational behavior, we develop a multilevel model of learning
      from failure, where perceived characteristics of the events, group composition
      and dynamics, and the behavioral and structural arrangements of health care
      organizations are proposed to play important roles. PRACTICAL IMPLICATIONS: Our
      model highlights factors that facilitate learning from failure and others that
      impede it. Awareness and attention to these factors can help health care managers
      extract learning from failures, like preventable adverse events, and may
      ultimately contribute to reducing the occurrence of preventable adverse events
      and improving quality of care.

PMID- 18075443
TI  - High-performing and low-performing nursing homes: a view from complexity science.
AB  - BACKGROUND: There continues to be concern for the quality of care and quality of
      life for nursing home residents. Some scientists have turned their attention to
      viewing nursing homes as complex adaptive systems to inform our understanding of
      organizational performance. PURPOSE: The purpose of this study was to describe
      the working conditions in four nursing homes-two high performing and two low
      performing-through the lens of complexity science theory. METHODS: A qualitative
      case study approach was used to examine four nursing homes. Extreme case examples
      high- and low-performing nursing homes-were purposefully selected. More than 100
      hr of observation, 70 formal interviews, numerous informal interviews, and
      document review were the primary data collection methods. FINDINGS: Using select
      complexity science principles added richness to the analysis, highlighting the
      stark contrast between the high- and low-performing nursing homes. Leaders in the
      high-performing homes behaved congruently with the nursing home's stated and
      lived mission by fostering connectivity among staff, ample information flow, and
      the use of cognitive diversity. In contrast, leadership in low-performing homes
      behaved disharmoniously with the stated mission, which confused and eroded trust
      and relationships among staff members, contributed to poor communication, and
      fostered role isolation and discontinuity in resident care. PRACTICE
      IMPLICATIONS: The study offers insights into the importance of mission- and
      values-based leadership behaviors, suggesting that an overuse of mechanistic,
      linear command-and-control approaches to improving care, such as punitive
      measures to insist on regulatory compliance, will do little to ultimately improve
      care. Rather, relationship-centered leadership that embraces co-management and
      mutual shaping of resident care complements doing the right thing for residents
      from a values-based shared experience. Examples of practice implications include
      developing a strong, coherent organizational mission; having fewer, more flexible
      rules to foster creativity; and allowing lateral decision making.

PMID- 18075444
TI  - A study of the effects of innovative and efficient practices on the performance
      of hospice care organizations.
AB  - BACKGROUND: Due to changes in social norms, funding initiatives, and other
      environmental factors, the business of hospice care has significantly evolved
      over the past 40 years. There has been an influx of for-profit firms, increased
      consolidation, and significant funding changes. We have witnessed a growth in
      utilization rates, an increase in insurance coverage, and improved governmental
      funding. Hospice care organizations have responded to these pressures by pursuing
      more efficient and innovative business practices. PURPOSE: Drawing upon
      institutional theory, this study seeks to address whether quality of care
      provided to hospice patients is affected as organizations respond to
      environmental pressures for innovative and efficient business practices.
      METHODOLOGY/APPROACH: This study uses hierarchical regression to analyze data
      from 111 hospices in California. FINDINGS: Innovative practices are positively
      related to quality of care. However, efficient practices have no significant
      relationship with quality of care. PRACTICAL IMPLICATIONS: It appears that
      incorporating innovative practices is positively related to quality of care.
      Although cost containment may be necessary for continued survival, efficiency
      improvement efforts do not seem to lead to improved quality of care.

PMID- 18075445
TI  - Organizational and environmental effects on voluntary and involuntary turnover.
AB  - BACKGROUND: There are few studies of voluntary and involuntary turnover in the
      nursing home literature. Previous research in this area has focused mainly on the
      linear effects of individual and organizational characteristics on total
      turnover. PURPOSES: The purpose of this study was to examine both linear and
      nonlinear effects of organizational and environmental conditions on voluntary and
      involuntary nursing home staff turnover. METHODOLOGY/APPROACH: We analyzed both
      primary and secondary data on 854 nursing homes in six states. A negative
      binomial regression model was used to study both linear and curvilinear effects
      of organizational and environmental factors on voluntary and involuntary turnover
      among registered nurses, licensed practical nurses, and nurse aides. FINDINGS:
      Staffing levels and deficiency citations were the organizational characteristics
      most consistently linked with turnover among all nurse types. Links were also
      found between unemployment and type of location (urban or rural) and turnover,
      indicating that the economic environment is influential for retention. PRACTICE
      IMPLICATIONS: The results of this study support the notion that policy makers
      need to consider both the organization and the environment when evaluating the
      nature of nursing home staff turnover. The findings also offer further evidence
      that the antecedents of voluntary and involuntary turnover are not necessarily
      the same.

PMID- 18075446
TI  - Team dynamics and team empowerment in health care organizations.
AB  - BACKGROUND: Despite the growing pervasiveness of team-based job designs in health
      care organizations, there is a degree of uncertainty and ambiguity about the
      process through which teams affect outcomes. PURPOSE: This research adds to our
      understanding of the process by which team dynamics affects team member
      attitudes. It investigates the role of team empowerment as a mediator in the
      relationships between team context, team atmosphere, job satisfaction, and
      organizational commitment. METHODOLOGY: Multiple regression analysis is used to
      test for the mediating effect of team empowerment in the relationships that team
      context and team atmosphere have with job satisfaction and organizational
      commitment. FINDINGS: Team empowerment mediates the relationships of team context
      and team atmosphere with job satisfaction and organizational commitment. PRACTICE
      IMPLICATIONS: Although adopting team-based job designs is an important first
      step, attention must also be paid to the context and atmosphere of such teams.
      Better outcomes will be achieved when team members perceive a supportive team
      atmosphere and an empowering team context with clear and jointly developed goals,
      an appropriate mix of skills and expertise, and rewards linked to team
      performance.

PMID- 18075449
TI  - It's no longer enough to advance the profession.

PMID- 18075447
TI  - Impact of perioperative systemic steroids on surgical outcomes in patients with
      chronic rhinosinusitis with polyposis: evaluation with the novel Perioperative
      Sinus Endoscopy (POSE) scoring system.
AB  - OBJECTIVES/HYPOTHESIS: The objective of this randomized, double-blind, placebo
      controlled study was to assess the effect of perioperative systemic steroids on
      subjective and objective surgical outcomes for patients undergoing endoscopic
      sinus surgery (ESS) for chronic rhinosinusitis with polyposis (CRSwP). The
      secondary objective was to begin validation of the newly developed Perioperative
      Sinus Endoscopy (POSE) scoring system. METHODS: Patients who had failed maximal
      medical therapy and were scheduled to undergo ESS were eligible for the study.
      Participants were randomized to receive either 30 mg of prednisone or placebo for
      5 days preoperatively and 9 days postoperatively. Operative and baseline clinical
      data were collected using the Lund-McKay staging system including its Sinus
      Symptom Questionnaire as well as additional data regarding mucosal health, the
      technical difficulty of surgery, and endoscopic data using the Lund-Kennedy
      Endoscopic Score (LKES) and POSE scale. Data were also collected at 2 weeks, 1
      month, 3 months, and 6 months postoperatively. A sample size of 24 was calculated
      to detect a clinically relevant difference between groups of 40%. Routine
      statistical comparisons were performed as were repeated measures analysis of
      variance with Bonferroni adjustment because of the multiple comparisons
      performed. To address the secondary objective, data were also collected at all
      postoperative time points using the POSE instrument, which was designed with the
      intention of enhancing face validity and responsiveness to change. Comparisons
      were performed between the POSE and LKES, including assessment of sensitivity to
      change, correlation between the two scales, and correlation with symptom scores.
      RESULTS: Twenty-six patients participated in the study. Operative data
      demonstrated a significantly higher percentage of severely inflamed sinonasal
      mucosa in patients not pretreated with systemic steroids, which was associated
      with technically more difficult surgery in the estimation of the operating
      surgeon. In terms of postoperative symptoms, there was no difference between
      treatment groups, with both placebo and prednisone significantly improved over
      baseline up to 4 weeks postoperatively. Endoscopic assessment of patients
      postoperatively demonstrated a treatment effect (P < .05), with clinically
      healthier cavities seen in patients treated with prednisone up to 6 months
      postoperatively as compared with baseline (P < .001), although the strongest
      effect was seen at the 2-week time point. In comparing the two endoscopic scales,
      the POSE and LKES correlated highly (R > 0.70; P < .001) both in terms of
      absolute score and change in score. There is some evidence that the POSE score
      may be more sensitive to change than the LKES, and the POSE scores did correlate
      more strongly with symptom scores than the LKES, although both endoscopic scores
      correlated only weakly with symptom scores. CONCLUSIONS: The data presented in
      this study support the practice of administering preoperative systemic steroids
      to patients undergoing ESS for CRSwP. Furthermore, in the practice of surgeons
      who provide intensive postoperative care post-ESS, including debridement and
      medical therapy based on the endoscopic findings, there is evidence to support
      administering systemic steroids in the postoperative period. The POSE scoring
      system compares favorably with the LKES and may confer advantages in terms of
      face/content validity and responsiveness to change and is worthy of further
      validation.

PMID- 18075450
TI  - One opioid does not fit all.

PMID- 18075451
TI  - Understanding chronic cough.

PMID- 18075455
TI  - COPD: your role in early detection.

PMID- 18075457
TI  - Breaking the ties of nicotine dependence.

PMID- 18075460
TI  - Single nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter mRNA
      expression.
AB  - OBJECTIVES: Epidemiological studies documented associations between single
      nucleotide polymorphisms (SNPs) in the nucleotide excision repair gene XPD/ERCC2
      and cancer risk. Little is known, however, about the underlying mechanisms for
      these associations. We explored a novel mechanism that could further explain the
      reported risk-modifying effect of these SNPs on disease susceptibility. METHODS:
      Using quantitative real-time polymerase chain reaction, we examined the
      relationship between three SNPs in the XPD gene (R156R in exon 6, D312N in exon
      10 and K751Q in exon 23) and mRNA levels as a potential mechanism by which these
      SNPs could alter DNA repair capacity and affect disease risk. To further
      investigate the mechanism(s) by which these SNPs alter mRNA transcription levels,
      we performed a localized Mfold structure analysis on the mRNA sequence
      surrounding the studied SNPs. RESULTS: All three SNPs studied, alone and in
      combination, significantly decreased constitutive XPD mRNA levels (P<0.003) in
      lymphocytes of healthy subjects. The decrease in mRNA levels was significantly
      greater in smokers and was exacerbated by smoking duration and intensity. The
      decrease was more pronounced in older than in younger subjects. The R156R and the
      K751Q polymorphisms were predicted to alter mRNA secondary structure, indicating
      that these SNPs potentially affect local folding and mRNA stability. CONCLUSIONS:
      Our results provide novel mechanistic explanations for epidemiological studies
      linking these SNPs to elevated cancer risk and emphasize the importance of
      comprehensively investigating the effect of both synonymous and nonsynonymous
      SNPs as risk modifiers by considering their potential effects on gene expression,
      protein translation and functions.

PMID- 18075461
TI  - Effects of rifampicin on global gene expression in human small intestine.
AB  - OBJECTIVES: The small intestinal wall serves as an important barrier for the
      entry of foreign substances into the organism. Of particular importance are
      enzymes and transporters that can inactivate or prevent the uptake of many
      xenobiotics including drugs. Some of the genes encoding these proteins are
      transcriptionally activated by xenobiotics, a response well studied in liver but
      less so in the intestine. The effect of the inducer drug rifampicin on intestinal
      cells was therefore evaluated both in vivo and in vitro. METHODS: Seven healthy
      volunteers were treated with rifampicin for 9 days and the global gene expression
      profile was analysed in RNA from duodenal biopsies taken before and after drug
      treatment. The gene expression profile was also assessed in LS174T cells derived
      from a human colon adenocarcinoma after exposure to 10 micromol/l rifampicin for
      24 h. RESULTS: We identified 32 genes that were upregulated and two genes that
      were downregulated by rifampicin treatment in vivo. The list of rifampicin
      regulated transcripts expectedly included drug metabolizing enzymes and drug
      transporters, but also genes involved in lipid and amino acid metabolism as well
      as genes not previously recognized to be part of the adaptation of intestinal
      cells to xenobiotic exposure. Only a limited number of these rifampicin-regulated
      transcripts were however also regulated by rifampicin in LS174T cells.
      CONCLUSION: The similarities and differences of changes in gene expression after
      rifampicin treatment between duodenal biopsies and cell culture provide a new
      assessment of the extent and diversity of systems affected by drug exposure.

PMID- 18075462
TI  - A novel genetic marker for coronary spasm in women from a genome-wide single
      nucleotide polymorphism analysis.
AB  - OBJECTIVE: Coronary spasm plays an important role in the pathogenesis of variant
      angina and also ischemic heart diseases in general, and it is more likely to
      occur in angiographically normal coronary arteries than in stenotic coronary
      arteries. We previously found a -786T/C polymorphism in the 5'-flanking region of
      the endothelial nitric oxide synthase (eNOS) gene and reported that this
      polymorphism is associated with coronary spasm. We report on an investigation of
      the genetic factor(s) associated with coronary spasm utilizing a genome-wide case
      control study. METHODS AND RESULTS: We recruited 411 consecutive Japanese women
      (201 with coronary spasm; 210 controls) who were all underwent an acetylcholine
      provocation test. For single nucleotide polymorphism analysis (SNP), 116,204 SNPs
      were genotyped for 100 women (50 with coronary spasm; 50 controls) utilizing the
      Affymetrix GeneChip 100 K Set. Case-control studies were performed with 311 women
      (151 with coronary spasm; 160 controls) using the 10 lowest permutation P value
      SNPs from the initial SNP analysis. Finally, we discovered SNP rs10498345, a
      genetic marker for coronary spasm in Japanese women (Odds ratio=0.43, P=9.48x10(
      7)). Haplotype analysis showed that haplotype H2, the only haplotype containing
      the protective A allele at SNP rs10498345, was most strongly associated with
      coronary spasm (permutation P value <1x10(-4)). SNP rs10498345 was strongly
      associated with the vasoconstrictor response to acetylcholine. Northern blot
      analysis revealed a novel 4.7 kb RNA transcript, which lacked poly (A), nearby
      SNP rs10498345. CONCLUSIONS: SNP rs10498345 was strongly associated with coronary
      spasm in Japanese women utilizing genome-wide SNP analysis.

PMID- 18075463
TI  - Protein tyrosine kinase 2beta as a candidate gene for hypertension.
AB  - Protein tyrosine kinase 2beta (PTK2B) is a member of the focal adhesion kinase
      family and is activated by angiotensin II through Ca2+-dependent pathways. An
      evidence exists that PTK2B is involved in cell growth, vascular contraction,
      inflammatory responses, and salt and water retention through activation of the
      angiotensin II type 1 receptor. To examine the contribution of PTK2B, we
      sequenced the PTK2B gene using 48 patients with hypertension, identified 62
      genetic polymorphisms, and genotyped six representative single nucleotide
      polymorphisms in population-based case-control samples from 3655 Japanese
      individuals (1520 patients with hypertension and 2135 controls). Multivariate
      logistic regression analysis after adjustments for age, body mass index, present
      illness (hyperlipidemia and diabetes mellitus), and lifestyle (smoking and
      drinking) showed -22A>G to have an association with hypertension in men (AA vs.
      AG+GG: odds ratio=1.27; 95% confidence interval: 1.02-1.57; P=0.030). Another
      polymorphism, 53484A>C (K838T), in linkage disequilibrium with -22A>G showed a
      marginal association with hypertension in men (AA vs. AC+CC: odds ratio=1.25; 95%
      confidence interval: 0.99-1.57; P=0.059). Diastolic blood pressure was 1.6 mmHg
      higher in men with the AC+CC genotype of 53484A>C than those with the AA genotype
      (P=0.003), after adjustments for the same factors. These polymorphisms are in
      linkage disequilibrium with others in a range of 113 kb in PTK2B. The
      intracellular distribution of the recombinant PTK2B protein and that of the
      mutant protein with T838 were indistinguishable even after angiotensin II
      stimulation, both proteins localizing at a focal point in the peripheral area in
      the cells. Thus, a haplotype in PTK2B may play a role in essential hypertension
      in Japanese.

PMID- 18075464
TI  - Arg389Gly-beta1-adrenergic receptors determine improvement in left ventricular
      systolic function in nonischemic cardiomyopathy patients with heart failure after
      chronic treatment with carvedilol.
AB  - OBJECTIVE: Administration of the beta-adrenergic receptor blocker carvedilol to
      patients with chronic heart failure leads to clinically significant benefits,
      including improvement in left ventricular systolic function in some, but not all,
      patients. We sought to determine the basis of the variable effect obtained with
      carvedilol in patients with heart failure. Carvedilol blocks both beta1
      adrenergic and beta2-adrenergic receptors, and both receptors exist as
      polymorphisms. We aimed to determine whether these polymorphisms contribute to
      variability in response to carvedilol in patients with chronic heart failure.
      METHODS: We retrospectively and prospectively investigated 135 patients with
      nonischemic cardiomyopathy and chronic stable heart failure (New York Heart
      Association class II, III) treated with carvedilol. Baseline echocardiography was
      obtained before introduction of carvedilol and repeated after stabilization of a
      maximally tolerated dose of carvedilol (50-100 mg/day) for at least 1 year.
      Polymerase chain reaction and restriction fragment length polymorphism analysis
      were used to genotype beta1-adrenergic and beta2-adrenergic receptor
      polymorphisms. RESULTS: When grouped according to receptor polymorphisms patients
      were well matched for severity of heart failure, comorbidity and treatment. No
      significant difference was observed in baseline left ventricular ejection
      fraction (LVEF) between groups (P>0.05). After 1.5 years of treatment with
      carvedilol patients with Arg389Arg-beta1-adrenergic receptors had a significantly
      greater improvement in LVEF compared with Gly389 carriers (Arg389Arg 18.8%;
      Arg389Gly 9.4%; Gly389Gly 6.0%; P<0.001) whereas there were no differences
      attributable to other beta1-adrenergic and beta2-adrenergic receptor
      polymorphisms (P>0.05). CONCLUSION: In patients with nonischemic dilated
      cardiomyopathy, carvedilol leads to a significantly greater improvement in LVEF
      in patients with the Arg389Arg-beta1 adrenergic receptor phenotype.

PMID- 18075465
TI  - Promoter polymorphisms and allelic imbalance in ABCB1 expression.
AB  - OBJECTIVE: The ABCB1 (MDR1) gene, encoding the transporter P-glycoprotein, is
      known to act on a broad range of prescription medicines. For this reason a large
      number of studies have assessed the functional consequences of variation in this
      gene. Particular attention has focused on the ABCB1_3435C>T polymorphism, an
      exonic variant resulting in a synonymous change. This variant has been associated
      with mRNA, protein and serum levels, and with responses to a number of medicines.
      The results of association studies have, however, been variable and it is not
      currently clear whether this polymorphism is functional or is in linkage
      disequilibrium with functionally distinct alleles. RESULTS: To identify
      functional variation in the ABCB1 gene we assessed allelic imbalance by
      pyrosequencing cDNA from 80 lymphoblastoid B cell lines from the Centre d'Etude
      du Polymorphisme Humain (CEPH) collection, including 74 individuals heterozygous
      for 3435C>T. We found that the degree of ABCB1 allelic imbalance differed among B
      cell lines. In an effort to fine-map variants that influence the proportion of
      the two allelic mRNA species we genotyped representative common variations near
      the 3435C>T polymorphism by using a tagging single nucleotide polymorphism (SNP)
      approach. In one approach, we assessed in segregating families the impact of cis
      acting variants on mRNA levels by using allelic imbalance as the phenotype in a
      regression analysis that distinguishes the coupling arrangements (phase) among
      alleles. In a second approach, we assessed allelic imbalance levels in
      lymphoblastoid B-cell lines from unrelated HapMap individuals, and performed an
      association using tagSNPs in a 5-Mb region surrounding the gene. Two potential
      cis-acting variants, a promoter rs28656907/rs28373093 dinucleotide polymorphism
      (P=0.007) and the rs10245483 SNP (P=0.0003) located 2 Mb upstream from the gene,
      were predictors of ABCB1 expression. CONCLUSIONS: The study outlines a general
      experimental approach for fine mapping gene variants that influence mRNA
      expression by using cultured cell lines.

PMID- 18075466
TI  - Molecular and genetic association of interleukin-6 in tacrine-induced
      hepatotoxicity.
AB  - BACKGROUND: Tacrine, an anticholinesterase used to treat Alzheimer's disease
      (AD), leads to an increase in serum alanine aminotransferase (ALT) levels. The
      factors determining individual susceptibility are largely unknown. The purpose of
      this study was to investigate genetic predisposition. METHODS: Rats were
      administered single dose tacrine (3-40 mg/kg). After 6 and 24 h, hepatic gene
      expression was determined using the affymetrix rat U34A microarray. On the basis
      of the gene expression data, the IL6 gene was identified as a potential candidate
      for tacrine transaminitis susceptibility. Sixty-nine patients with AD on tacrine
      with or without transaminitis were genotyped for 17 IL6 polymorphisms. RESULTS:
      Serum aspartate aminotransferase levels in rats increased after tacrine (40
      mg/kg) administration. Forty-six and 29 genes showed significant upregulation at
      6 and 24 h, respectively, after administration, including the IL-6-regulated
      acute phase response genes alpha2-macroglobulin, fibronectin and haptoglobin.
      Five of the 17 IL6 polymorphisms studied in AD patients showed an association
      (P<0.05) with transaminitis [ALT>2 x upper limit of normal (ULN)]. An association
      existed between maximum ALT and area under curve for ALT over 15 weeks and an
      intronic polymorphism (P<0.01) and a 3'-variable nucleotide tandem repeat
      (P<0.05). Multilocus haplotype analysis showed one haplotype (which included the 
      597A, -572G, -174G and variable nucleotide tandem repeat-D alleles) had a
      frequency of 0.1 in patients with ALT values >2 x ULN, whereas it was absent in
      patients with ALT less than 2 x ULN (P=0.0093, Pcorrected=0.049). CONCLUSION: The
      IL6 genotype may act as a predisposing factor for tacrine transaminitis. This,
      however, requires further confirmatory functional studies. The role of acute
      dosing rodent models in identifying candidate genes associated with drug-induced
      liver injury in man deserves further study.

PMID- 18075467
TI  - Genetic regulation of dihydropyrimidinase and its possible implication in altered
      uracil catabolism.
AB  - OBJECTIVE: Dihydropyrimidine dehydrogenase (DPD) deficiency accounts for
      approximately 43% of grade 3-4 toxicity to 5-fluorouracil. There, however, remain
      a number of patients presenting with 5-fluorouracil-associated toxicity despite
      normal DPD enzyme activity, suggesting possible deficiencies in
      dihydropyrimidinase (DHP), encoded by the DPYS gene, and/or beta-ureidopropionase
      (BUP-1), encoded by the UPB1 gene. This study investigates the role of DPYS
      sequence variations in individuals with unexplained molecular basis of altered
      uracil catabolism. METHODS: This study included 219 asymptomatic healthy
      volunteers with known DPD enzyme activity and [2-13C]-uracil breath test (UraBT)
      profiles. All samples were genotyped for sequence variations in the DPYS gene
      using denaturing high-performance liquid chromatography (DHPLC) and Surveyor
      enzyme digestion with confirmation by direct sequencing. Site-directed
      mutagenesis and expression analysis were performed to determine the effect of the
      identified nonconservative mutations on DHP enzyme activity. RESULTS: Seven
      previously reported and 11 novel sequence variations were identified, including
      three nonconservative mutations; two of which (L7V and 1635delC) demonstrated
      decreased DHP activity when expressed in the RKO cell line (P=0.25). The P values
      were not significant due to the small sample size (n=3); however, a modified [2
      13C]-uracil breath test, the 13C-dihydrouracil breath test, was administered to
      four volunteers to confirm that the 1635delC mutation does in fact reduce in-vivo
      DHP activity. CONCLUSION: Data presented in this study demonstrate that
      alterations of uracil catabolism are not limited to DPD deficiency, and that
      inactivating mutations in DHP might impair uracil catabolism in cases of normal
      DPD activity.

PMID- 18075468
TI  - CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time
      course of prolactin response to perphenazine.
AB  - OBJECTIVES: We observed that CYP2D6 contributes to pharmacodynamic tissue
      sensitivity to perphenazine as measured by the areas under the curve (AUCs)
      expressed as a ratio (prolactin-AUC0-6/perphenazine-AUC0-6) in Chinese Canadians
      [Pharmacogenetics and Genomics 2007; 17:339-347]. As genetic heterogeneity in
      drug targets can influence drug response, we sought to further evaluate the
      contribution of CYP2D6 to pharmacodynamic sensitivity in our previous study
      sample in tandem with DRD2, the primary molecular target for perphenazine.
      METHODS: Genotyping for DRD2 Taq1A, -141C ins/del and Ser311Cys functional
      polymorphisms was performed using PCR-restriction-fragment length polymorphism
      methods. RESULTS: After controlling for DRD2 polymorphisms, CYP2D6 was a
      significant predictor of pituitary pharmacodynamic tissue sensitivity to
      perphenazine (P=0.024; power=80.4%). Taq1A polymorphism significantly influenced
      the time course of prolactin response (P=0.039; power=70%). A1/A1 genotype
      displayed a higher prolactin elevation 2 h after perphenazine administration
      (P=0.02). Patients with -141C ins/ins genotype showed a strong trend toward a 38%
      larger prolactin AUC compared with the -141C ins/del genotypic group (P=0.07).
      CONCLUSIONS: CYP2D6 seems to be an independent contributor to pituitary
      pharmacodynamic tissue sensitivity to perphenazine after accounting for DRD2
      functional polymorphisms. The A1 allele of the Taq1A polymorphism was previously
      shown to decrease D2 receptor density in vitro and in neuroimaging studies in
      vivo. At a given antipsychotic dose, individuals with A1 allele might thus
      achieve a higher DRD2 antipsychotic occupancy, which is consistent with an
      increased prolactin elevation in the A1/A1 genotype in this study. These findings
      provide a basis for further studies on the endogenous substrates of CYP2D6 and
      the rational selection of candidate genes for long-term consequences of
      antipsychotic-induced hyperprolactinemia (e.g. susceptibility to breast and
      prostate cancers).

PMID- 18075469
TI  - Two novel mutations in the BCHE gene in patients with prolonged duration of
      action of mivacurium or succinylcholine during anaesthesia.
AB  - BACKGROUND: Butyrylcholinesterase (BChE) hydrolyses the neuromuscular blocking
      agents, succinylcholine and mivacurium used during general anaesthesia.
      Hereditary low BChE activity may result in an extensively prolonged duration of
      action of these drugs, especially in patients who are homozygous for the atypical
      or silent variants. We present three novel mutations in the butyrylcholinesterase
      gene (BCHE) identified in three families in which a member had experienced
      severely prolonged duration of action of succinylcholine. METHODS: As the
      phenotypes of the three probands could not be established with certainty using
      conventional biochemical tests, DNA samples were collected from two of the
      probands and four relatives. Genotypes were determined using complete nucleotide
      sequencing. RESULTS: Three novel mutations were identified: BCHE*FS126, BCHE*I3E4
      14C and BCHE*328D. The proband in family 1 was genotyped as BCHE*115D*I3E4
      14C/BCHE*FS126, whereas the proband in family 3 was compound heterozygous for
      BCHE*328D and BCHE*142M. In both patients, BChE activity was below detection
      limit, and they experienced an extensively prolonged duration of action of
      succinylcholine. The proband in family 2 was not sequenced, but a relative was
      heterozygous for BCHE*FS126. BCHE*I3E4-14C was in linkage with a known silent
      variant. CONCLUSIONS: Two novel variants of BCHE are silencing the enzyme
      function. BCHE*FS126 results in a truncated protein lacking the active site and
      is therefore inactive. The second variant is BCHE*328D, also resulting in an
      inactive protein, as this change in amino acid is radical and furthermore
      situated in the gorge harbouring the active site. These variants result in
      extensively prolonged duration of action of succinylcholine.

PMID- 18075470
TI  - Association between caffeine intake and risk of Parkinson's disease among fast
      and slow metabolizers.
AB  - INTRODUCTION: Cytochrome P450 1A2 (CYP 1A2) is responsible for more than 90% of
      caffeine clearance. A polymorphic variant of CYP1A2 (-163C>A) (rs762551) is
      associated with high CYP1A2 inducibility. Both caffeine and its main metabolite,
      paraxanthine, may be neuroprotective. The association between caffeine intake and
      risk of Parkinson's disease (PD) in fast and slow caffeine metabolizers has not
      been compared. OBJECTIVE: In a case-control study, we analyzed the relationship
      between caffeine intake and risk of PD in both fast and slow caffeine
      metabolizers. METHODS: All the study participants were recruited prospectively,
      and interviewed for information on the amount and duration of caffeine intake.
      Genotyping of the CYP1A2 variant was carried out using the allelic discrimination
      method. RESULTS: Out of 1000 participants who were initially screened, 886
      consisting of 418 PD and 468 race, sex and age matched controls were included. No
      evidence existed to suggest any association between CYP1A2 and the onset of PD
      (P=0.08). A significant association was seen between caffeine intake and the
      onset of PD (P=2.01x10(-5)), with the odds ratio for moderate and high drinkers
      at 0.71 [95% confidence interval (CI): 0.50-1.00] and 0.47 (95% CI: 0.34-0.65),
      respectively against the low drinkers. Multivariate analysis revealed no evidence
      of any interaction effects of caffeine with CYP1A2 (P=0.956). CONCLUSION: The
      association between caffeine intake and risk of PD was similarly observed in both
      fast and slow caffeine metabolizers, supporting experimental evidence in animal
      models that both caffeine and its major metabolite, paraxanthine, are
      neuroprotective.

PMID- 18075471
TI  - Further evidence for association of GRK3 to bipolar disorder suggests a second
      disease mutation.
AB  - OBJECTIVES: Two genome-wide linkage surveys suggest chromosome 22q12 may contain
      a susceptibility locus for bipolar disorder (BPD) in the immediate region of the
      gene G protein receptor kinase-3 (GRK3). We previously published evidence that a
      single nucleotide polymorphism (SNP) in the promoter region of GRK3, designated
      P5, was associated with BPD. This SNP, however, was too rare (allele frequency
      0.007) to explain the evidence for linkage. METHODS: To identify other SNPs or
      haplotypes associated with illness, we have now sequenced an additional 28-kb
      genomic segment of GRK3 and tested an additional 35 SNPs for association with BPD
      in 181 Caucasian nuclear families. RESULTS: Transmission disequilibrium test
      analyses identified two closely related disease-associated haplotypes defined by
      four SNPs located upstream of the promoter region: transmission to
      nontransmission ratios=54:22 and 20:9, odds ratios=2.50 and 2.36, and P
      values=0.0009 and 0.05. The best P value remained significant after correction
      for multiple testing. These two haplotypes were found on an entirely different
      set of chromosomes from the previously identified SNP P5. They had a combined
      frequency of approximately 0.10 and, therefore, a much greater population
      attributable risk for disease than the previously identified P5 haplotype.
      CONCLUSIONS: These data provide evidence that at least two distinct haplotypes,
      and possibly two or more different underlying mutations, in GRK3 might be
      associated with BPD. These new findings add support for the hypothesis that a
      dysregulation in GRK3 expression alters signaling desensitization and thereby
      predisposes to the development of BPD.

PMID- 18075472
TI  - The MAOA promoter polymorphism, disruptive behavior disorders, and early onset
      substance use disorder: gene-environment interaction.
AB  - OBJECTIVES: Conduct, oppositional defiant, and attention deficit hyperactivity
      disorders, reflecting early antisociality and behavior dysregulation, are
      predictive of substance use disorders. Liabilities to these disorders share
      genetic and environmental variance. Parenting characteristics have been shown to
      influence development of antisociality, moderated by variation at the MAOA gene,
      which has also been associated with the risk for substance use disorders. To
      extend these findings, we tested the relationships between the MAOA promoter
      polymorphism (variable number tandem repeat), indices of child's perception of
      paternal and maternal parenting, and disruptive behavior disorders and substance
      use disorders. METHODS: A sample of 148 European-American males was assessed
      prospectively at ages from 10-12 to 18-19 years and genotyped for the monoamine
      oxidase A variable number tandem repeat. The Diagnostic and statistical manual of
      mental disorder-III-R diagnoses were obtained using standard methodology.
      Parenting was assessed using a scale summarizing the child's evaluation of the
      parenting style (parent's behavior toward him, parental emotional distance and
      involvement). Correlation, logistic regression, and Cox proportional hazard
      regression analysis was used to determine the relationships between the
      variables. RESULTS: The strength of association between parenting index and
      conduct and attention deficit hyperactivity disorders depended on the MAOA
      genotype. Unlike earlier findings, the parenting-risk relationships were observed
      in the 'high-' rather than 'low-activity' genotypes. The strength and direction
      of relationships depended on the parental sex. The MAOA polymorphism's
      association with the risk for substance use disorders was detected when parenting
      was controlled for. CONCLUSIONS: The results are consistent with the contribution
      of the MAOA gene, parenting style and their interactions to variation in the risk
      for early onset behavior disorders and liability to substance use disorders.

PMID- 18075473
TI  - HTF9C gene of 22q11.21 region associates with schizophrenia having deficit
      sustained attention.
AB  - OBJECTIVE: A region at chromosome 22q11.21 has been reported to potentially
      harbor a candidate gene for schizophrenia, ZDHHC8 (zinc finger, DHHC domain
      containing 8; also annotated as KIAA1292) in a number of studies. This finding
      has been replicated in Han Chinese, but not in other ethnicity-specific studies.
      For further support from within the Han Chinese ethnic group, we selected two
      single nucleotide polymorphisms (SNP) located at the distal 5'-end (rs1633445;
      intron 10 of HpaII tiny fragments locus 9C, HTF9C) and the intron 4 (rs175174) of
      ZDHHC8 gene to test if these were associated with schizophrenia in a study sample
      of Taiwan. METHODS: A total of 218 schizophrenia families with at least two
      affected siblings participated in this study. These two SNPs were genotyped using
      matrix-assisted laser desorption/localization ionization time of flight (MALDI
      TOF) mass spectrometry. RESULTS: Significant associations with schizophrenia were
      not shown from these two SNPs. After stratifying schizophrenia according to the
      deficit and the nondeficit of sustained attention assessed by the Continuous
      Performance Test, the rs1633445 showed significant association with schizophrenia
      in the presence of a deficit in sustained attention (P<0.04). CONCLUSION: SNP
      rs1633445 of the HTF9C gene may be associated with a deficit in sustained
      attention within schizophrenia, in a Taiwanese cohort. The deficit of sustained
      attention may be an endophenotype of schizophrenia, and warrants further study.

PMID- 18075474
TI  - Serotonin transporter polymorphism and borderline or antisocial traits among low
      income young adults.
AB  - OBJECTIVES: The short allele of the serotonin transporter linked polymorphic
      region, 5HTTLPR has been associated with anxiety, major depressive disorder and
      suicidality. The impulsive self- and other-damaging behaviors seen in borderline
      personality disorder and antisocial personality disorder also have substantial
      comorbidity with depression but are associated with more severe environmental
      stressors. This study tested the hypothesis of an association between the short
      allele of the 5HTTLPR and borderline or antisocial traits in young adulthood.
      METHODS: The 5HTTLPR was genotyped among 96 young adults from low to moderate
      income families (62 adults without and 34 adults with borderline personality
      disorder or antisocial personality disorder traits). Traits of borderline and
      antisocial personality disorders were assessed with the Structured Clinical
      Interview for Diagnosis-Axis II. RESULTS: The number of short 5HTTLPR alleles
      were significantly related to incidence of borderline personality disorder or
      antisocial personality disorder traits and also to each set of traits
      independently. Male sex and quality of care in infancy were also associated with
      incidence of borderline personality disorder and antisocial personality disorder
      traits but did not account for the association with the short allele. Depressive
      disorders were not associated with the short allele in this sample. CONCLUSIONS:
      Young adults of lower socioeconomic status who carry the short 5HTTLPR allele may
      be especially vulnerable to developing antisocial or borderline traits by young
      adulthood.

PMID- 18075475
TI  - Irritable assault and variation in the COMT gene.
AB  - Aggression is associated with the 'low' activity allele (Met) of the functional
      Val158Met polymorphism among people with schizophrenia spectrum disorders
      relative to the 'high' activity (Val) allele. We examined this polymorphism in a
      sample of 112 people with axis II personality disorders. Participants completed
      the Buss Durkee Hostility Inventory. Two single nucleotide polymorphisms in the
      COMT gene were genotyped in these participants classified as 'white' according to
      US Census Bureau definitions. We failed to observe an association between the
      Val158Met allele and aggression but observed an association between self-reported
      aggression and the G allele of a biallelic polymorphism located in the 3'' UTR
      (rs16559). This allele is less prevalent among schizophrenics and is associated
      with lower COMT expression in the brain. These findings provide limited support
      for a role of COMT in modulating aggressive behavior, and are extended to people
      with personality disorders.

PMID- 18075476
TI  - GPR50 is not associated with childhood-onset mood disorders in a large sample of
      Hungarian families.
AB  - We investigated the relationship of the gene for the X-linked orphan G protein
      coupled receptor (GPR50) to childhood-onset mood disorders in a sample of 384
      families with 468 affected children and adolescents collected in Hungary. Our
      choice of this gene for study was based on a previous report of an association of
      GPR50 with bipolar disorder and major depressive disorder. A significant
      association with the deletion allele of an insertion/deletion polymorphism
      (Delta502-505) located in exon 2 had been reported in a sample of 226 patients
      with major depressive disorder and 264 patients with bipolar disorder. The
      association was more significant in females compared with males in those samples.
      We used for this study a polymorphism in complete linkage disequilibrium with the
      Delta502-505 polymorphism, Thr532Ala (rs561077), and two additional
      polymorphisms, Val606Ile (rs13440581) and an intronic polymorphism (rs2072621).
      We found no evidence for an association for the markers analyzed individually,
      nor for haplotypes of these markers. Further, we found no evidence of association
      when the results were analyzed in girls only (n=215). We, therefore, failed to
      replicate the previous association of this gene with mood disorders.

PMID- 18075477
TI  - Association between serotonin transporter genotype and extraversion.
AB  - Despite the long-standing recognition that extraversion is partially heritable,
      few specific genes have been found to be associated significantly with this
      personality trait. The purpose of this study was to examine the association
      between a functional genetic polymorphism of the serotonin transporter promoter
      region (5-HTTLPR) and extraversion. Caucasian participants (N=183) were genotyped
      for the 5-HTTLPR; extraversion scores for participants homozygous for the short
      allele (s/s) were compared with those participants carrying at least one long
      allele (s/l and l/l). An s/s genotype at 5-HTTLPR was significantly associated
      with self ratings of reduced extraversion (P=0.012); presence versus absence of
      the long allele explained 3.4% of the variance in extraversion. These findings
      provide support for the effect of the 5-HTTLPR, and for the serotonergic system
      more broadly, on behaviors related to extraversion.

PMID- 18075478
TI  - A putative regulatory subunit (NR3A) of the NMDA receptor complex as candidate
      gene for susceptibility to schizophrenia: a case-control study.

PMID- 18075479
TI  - Lack of association between polymorphisms in the 5' upstream region of the DISC1
      gene and mood disorders.

PMID- 18075480
TI  - Association analysis of the metabotropic glutamate receptor type 3 gene (GRM3)
      with schizophrenia.

PMID- 18075481
TI  - Association study between Tourette's syndrome and polymorphisms of noradrenergic
      genes (ADRA2A, ADRA2C).

PMID- 18075483
TI  - Depressed heart rate variability is associated with high IL-6 blood level and
      decline in the blood pressure in septic patients.
AB  - Depressed heart rate variability (HRV) in septic patients is known to be
      associated with poor outcome. However, neither etiology of depression of HRV nor
      its clinical significance has been clearly determined. Because hypercytokinemia
      plays an important role in sepsis, we investigated the relationships between
      depressed HRV and IL-6 blood level. The subjects of this study were 45 septic
      patients treated in our intensive care unit. IL-6 blood level upon admission
      exhibited significant negative correlations with two HRV indices, low-frequency
      power (LF) (r = -0.76; P < 0.01) and high-frequency power (HF) (r = -0.53; P <
      0.01). Multivariate analysis revealed strong correlations between IL-6 blood
      level and LF (P = 0.01) and HF (P = 0.01), respectively, even when the effects of
      patient background factors and therapeutic intervention were taken into account.
      Among the patients who developed septic shock, a high IL-6 blood level and a low
      LF were observed in both the survivor and nonsurvivor groups on the day of
      admission. The HF was lower than normal at the same time points in both groups.
      However, the HF was significantly higher in the nonsurvivor group than in the
      survivor group. By the time of discharge from the intensive care unit, both IL-6
      blood level and HRV indices had become significantly closer to the normal ranges
      in the survivor group, but not in the nonsurvivor group. A significant negative
      correlation was observed between LF upon admission and percent decline in blood
      pressure (r = -0.76, P < 0.01). These findings indicate that reduction in HRV
      indices is associated with hypercytokinemia, indicating that the autonomic
      nervous system and the inflammatory response mediated by the cytokine network
      affect each other. These results also suggest that depression of HRV is closely
      related to rapid changes in blood pressure. Thus, heart rate variability indices
      are associated with both the severity and poor outcome of sepsis.

PMID- 18075484
TI  - Putting a stop to thrombi.
AB  - Learn how anticoagulants and platelet-active drugs protect your patient from
      myocardial infarction, ischemic stroke, and other life-threatening thrombotic
      events.

PMID- 18075485
TI  - Increases in age-group-specific injury mortality--United States, 1999-2004.
AB  - From 1979 to 1999, total injury mortality rates declined overall in the United
      States, despite increases in suicide rates in the late 1980s and in homicide
      rates in the early 1990s (CDC, unpublished data, 2007). From 1999 to 2004,
      however, total injury mortality rates increased 5.5%, from 53.3 to 56.2 per
      100,000 population, the first sustained increase in 25 years. To assess this
      increase, CDC analyzed the most recent data from the National Vital Statistics
      System (NVSS). This report summarizes the results of that analysis, which
      determined that U.S. mortality rates increased from 1999 to 2004 for
      unintentional injuries, suicides, and injuries of undetermined intent; homicide
      rates were stable. Among persons aged 45-54 years, the total injury mortality
      rate increased 24.5%, including an 87.0% increase in the mortality rate from
      unintentional poisoning (most commonly drug poisoning) and a 48.0% increase in
      suicide by hanging/suffocation. Among persons aged 20-29 years, the total injury
      mortality rate increased 7.7%, including a 92.5% increase in the death rate from
      unintentional poisoning and a 31.7% increase in suicide by hanging/suffocation.
      Parallel increases in multiple categories and mechanisms of injuries within these
      two age groups suggest an increase in one or more shared risk factors (e.g., drug
      abuse); prevention programs that focus on shared risk factors might help reduce
      deaths from injuries.

PMID- 18075486
TI  - Outbreak of cutaneous larva migrans at a children's camp--Miami, Florida, 2006.
AB  - On July 19, 2006, the director of a children's aquatic sports day camp notified
      the Miami-Dade County Health Department (MDCHD) of three campers who had received
      a diagnosis of cutaneous larva migrans (CLM), or "creeping eruption," a skin
      condition typically caused by dog or cat hookworm larvae of the genus
      Ancylostoma. MDCHD conducted an investigation to determine the source and
      magnitude of the outbreak and prevent additional illness. This report summarizes
      the results of that investigation, which identified exposure to cat feces in a
      playground sandbox as the likely source of infection. Although CLM outbreaks are
      reported rarely to the Florida Department of Health, evidence indicates that CLM
      is a potential health hazard in Florida. This disease cluster highlights the
      importance of appropriate environmental hygiene practices and education in
      preventing CLM.

PMID- 18075487
TI  - Update: influenza activity--United States, September 30-December 1, 2007.
AB  - During September 30-December 1, 2007, influenza activity remained low in the
      United States. This report summarizes U.S. influenza activity since September 30,
      the start of the 2007-08 influenza season.

PMID- 18075488
TI  - Preconception and interconception health status of women who recently gave birth
      to a live-born infant--Pregnancy Risk Assessment Monitoring System (PRAMS),
      United States, 26 reporting areas, 2004.
AB  - PROBLEM/CONDITION: In 2006, CDC published recommendations to improve health and
      health care for women before pregnancy and between pregnancies (CDC.
      Recommendations to improve preconception health and health care--United States: a
      report of the CDC/ATSDR Preconception Care Work Group and the Select Panel on
      Preconception Care. MMWR 2006;55[No. RR-6]). The Pregnancy Risk Assessment
      Monitoring System (PRAMS) provides data concerning maternal behaviors, health
      conditions, and experiences for women in the United States who have delivered a
      live birth. REPORTING PERIOD COVERED: 2004. DESCRIPTION OF SYSTEM: PRAMS is an
      ongoing, state- and population-based surveillance system designed to monitor
      selected maternal behaviors and experiences that occur before, during, and after
      pregnancy among women who deliver live-born infants in selected states and cities
      in the United States. PRAMS employs a mixed mode data-collection methodology; up
      to three self-administered questionnaires are mailed to a sample of mothers, and
      nonresponders are followed up with telephone interviews. Self-reported survey
      data are linked to selected birth certificate data and weighted for sample
      design, nonresponse, and noncoverage to create annual PRAMS analysis data sets
      that can be used to produce statewide estimates of perinatal health behaviors and
      experiences among women delivering live infants. This report summarizes data from
      26 PRAMS reporting areas that collected data during 2004 and that had achieved
      overall weighted response rates of > or =70% and had weighted data available by
      the time the analysis was conducted in January 2007. Data are reported on
      indicators regarding 18 behaviors and conditions that are relevant to
      preconception (i.e., prepregnancy) health and health care and 10 that are
      relevant to interconception (i.e., postpartum) health and health care. The number
      of questions that were administered varied by site; certain questions were not
      asked for all reporting areas. RESULTS: With respect to preconception maternal
      behaviors and experiences, mean overall prevalence was 23.2% for tobacco use,
      50.1% for alcohol use, 35.1% for multivitamin use at least four times a week,
      53.1% for nonuse of contraception among women who were not trying to become
      pregnant, 77.8% for ever having a dental visit before pregnancy, 30.3% for
      receiving prepregnancy health counseling, 3.6% for experiencing physical abuse,
      and 18.5% for experiencing at least four stressors before pregnancy. With respect
      to preconception maternal health conditions, mean overall prevalence was 13.2%
      for women being underweight (body mass index [BMI]: <19.8), 13.1% for being
      overweight (BMI: 26.0-29.0), and 21.9% for being obese (BMI: > or =29.0). Mean
      overall prevalence was 1.8% for having diabetes, 6.9% for asthma, 2.2% for
      hypertension, 1.2% for heart problems, and 10.2% for anemia. Among women with a
      previous live birth, the mean overall prevalence of having a previous low birth
      weight infant was 11.6% and of having a previous preterm infant was 11.9%. With
      respect to interconception maternal behaviors and experiences, mean overall
      prevalence was 17.9% for tobacco use, 85.1% for contraceptive use, 15.7% for
      having symptoms of depression, and 84.8% for having social support. Mean overall
      prevalence was 7.5% for the most recent infant being born low birth weight, 10.4%
      for having a recent preterm infant, 89.3% for having a check-up, 89.0% for
      receiving contraceptive use counseling, 30.4% for having a dental visit, and
      48.6% for receiving services from the Special Supplemental Nutrition Program for
      Women, Infants, and Children (WIC). Results varied by maternal age,
      race/ethnicity, pregnancy intention, and health insurance status. For certain
      risk behaviors and health conditions, mean overall prevalence was higher among
      women aged <20 years, black women, women whose pregnancies were unintended, and
      women receiving Medicaid; however, no single subgroup was consistently at highest
      risk for all the indicators examined in this report. INTERPRETATION: PRAMS
      results varied among reporting areas. The prevalence estimates in the majority of
      reporting areas and for the majority of indicators suggest that a substantial
      number of women would benefit from preconception interventions to ensure that
      they enter pregnancy in optimal health. The results also demonstrate disparities
      among age and racial/ethnic subpopulations, especially with respect to
      prepregnancy medical conditions and access to health care both before conception
      and postpartum. Differences also exist in health behaviors between women who
      reported intended and unintended pregnancies. PUBLIC HEALTH ACTION: Maternal and
      child health programs can use PRAMS data to monitor improvements in maternal
      preconception and interconception behaviors and health status. The data presented
      in this report, which were collected before publication of CDC's recommendations
      to improve preconception health and health care in the United States, can be used
      as a baseline to monitor progress toward improvements in preconception and
      interconception health following publication of the recommendations. These data
      also can be used to identify specific groups at high risk that would benefit from
      targeted interventions and to plan and evaluate programs aimed at promoting
      positive maternal and infant health behaviors, experiences, and reproductive
      outcomes. In addition, the data can be used to inform policy decisions that
      affect the health of women and infants.

PMID- 18075489
TI  - Contributions of dopamine D1, D2, and D3 receptor subtypes to the disruptive
      effects of cocaine on prepulse inhibition in mice.
AB  - Deficits in prepulse inhibition (PPI) of startle, an operational measure of
      sensorimotor gating, are characteristics of schizophrenia and related
      neuropsychiatric disorders. Previous studies in mice demonstrate a contribution
      of dopamine (DA) D(1)-family receptors in modulating PPI and DA D(2) receptors
      (D2R) in mediating the PPI-disruptive effects of amphetamine. To examine further
      the contributions of DA receptor subtypes in PPI, we used a combined
      pharmacological and genetic approach. In congenic C57BL/6 J wild-type mice, we
      tested whether the D1R antagonist SCH23390 or the D2/3R antagonist raclopride
      would attenuate the effects of the indirect DA agonist cocaine (40 mg/kg). Both
      the D1R and D2/3R antagonists attenuated the cocaine-induced PPI deficit. We also
      tested the effect of cocaine on PPI in wild-type and DA D1R, D2R, or D3R knockout
      mice. The cocaine-induced PPI deficit was influenced differently by the three DA
      receptor subtypes, being absent in D1R knockout mice, partially attenuated in D2R
      knockout mice, and exaggerated in D3R knockout mice. Thus, the D1R is necessary
      for the PPI-disruptive effects of cocaine, while the D2R partially contributes to
      these effects. Conversely, the D3R appears to inhibit the PPI-disruptive effects
      of cocaine. Uncovering neural mechanisms involved in PPI will further our
      understanding of substrates of sensorimotor gating and could lead to better
      therapeutics to treat complex cognitive disorders such as schizophrenia.

PMID- 18075490
TI  - Gray matter changes in late life depression--a structural MRI analysis.
AB  - Multiple brain morphometric changes have been reported in late-life depression
      (LLD), mostly in studies comparing volumes of circumscribed brain areas. The aim
      of our study is to characterize the volumetric changes of multiple gray matter
      regions in relation to age of onset/duration of illness. We predicted that the
      association of gray matter volumes with total duration of illness and age of
      onset would differ depending on whether the region was susceptible to the toxic
      effects of chronic exposure to cortisol or to the vascular/neurodegenerative
      changes accompanying prodromal dementia. Seventy-one elderly depressed subjects
      were studied along with thirty-two comparison subjects. High-resolution T1
      weighted brain MRIs were processed using an automated labeling pathway technique.
      To protect against type-I error, we combined the right and left hemisphere volume
      data. We sampled 24 regions of interest (ROIs). We used the primary visual cortex
      volume to normalize for individual variations in brain size. LLD Subjects had
      smaller volumes than non-depressed subjects in 17 of the 24 examined ROIs.
      Shorter duration of illness and later age of onset was correlated with smaller
      volumes of parahippocampal area and parietal inferior area. A later age of onset
      was also correlated with smaller volumes of several frontal and temporal areas,
      cingulum, and putamen. Our findings support a dementia prodrome model more
      strongly than a toxic stress model in this group of subjects. However, it remains
      likely that both processes as well as other factors contribute to the
      heterogeneity of volumetric brain changes in LLD.

PMID- 18075492
TI  - The promnesic effect of G-protein-coupled 5-HT4 receptors activation is mediated
      by a potentiation of learning-induced spine growth in the mouse hippocampus.
AB  - Pharmacological modulation of synaptic efficacy is a prominent target in the
      identification of promnesic compounds. Here, we report that pretraining
      administration of the serotonin 5-HT(4) receptors (5-HT(4)Rs) partial agonist
      SL65.0155 enhances simultaneous olfactory discrimination performance and
      potentiates learning-induced dendritic spine growth in the mouse hippocampus.
      SL65.0155 does not affect spine density in the pseudo-trained mice and, by
      itself, does not promote spine growth. Injecting the 5-HT(4) antagonist RS39604
      prior to SL65.0155 prevents both the increase in performance and the additional
      formation of spines, thus confirming the 5-HT(4)Rs specificity of the observed
      effects. These findings provide evidence that 5-HT(4)Rs stimulation selectively
      increases experience-dependent structural plasticity in learning-activated
      hippocampal circuits.

PMID- 18075493
TI  - Lower phosphoinositide 3-kinase (PI 3-kinase) activity and differential
      expression levels of selective catalytic and regulatory PI 3-kinase subunit
      isoforms in prefrontal cortex and hippocampus of suicide subjects.
AB  - Phosphoinositide 3 (PI 3)-kinase is one of the key signaling enzymes that
      participates in a myriad of physiological functions in brain and is utilized by
      neurotrophins to mediate neuronal plasticity, cell survival, and inhibition of
      apoptosis for several neuronal subtypes. Our recent demonstration that expression
      of neurotrophic factors and activation of the receptor tyrosine kinase B are
      significantly altered in postmortem brain of suicide subjects led us to examine
      whether suicide brain is associated with alterations in PI 3-kinase signaling. In
      prefrontal cortex (PFC), hippocampus, and cerebellum of suicide (n=28) and
      nonpsychiatric control (n=21) subjects we examined catalytic activation of PI 3
      kinase, and mRNA and protein levels of regulatory (p85alpha, p85beta) and
      catalytic (p110alpha, p110beta) subunits of PI 3-kinase. It was observed that the
      catalytic activity of PI 3-kinase was significantly reduced in PFC and
      hippocampus of suicide subjects compared with nonpsychiatric control subjects.
      Competitive PCR analysis revealed significantly reduced mRNA expression of
      p85beta and p110alpha and increased expression of p85alpha subunit isoforms in
      PFC and hippocampus of suicide subjects. Alterations in these catalytic and
      regulatory subunits were accompanied by changes in their respective protein
      levels. These changes were not present in cerebellum of suicide subjects. Also,
      these changes were present in all suicide subjects irrespective of psychiatric
      diagnosis. Our findings of reduced activation and altered expression of specific
      PI 3-kinase regulatory and catalytic subunit isoforms demonstrate abnormalities
      in this signaling pathway in postmortem brain of suicide subjects and suggest
      possible involvement of aberrant PI 3-kinase signaling in the pathogenic
      mechanisms of suicide.

PMID- 18075491
TI  - Aging exacerbates depressive-like behavior in mice in response to activation of
      the peripheral innate immune system.
AB  - Exposure to peripheral infections may be permissive to cognitive and behavioral
      complications in the elderly. We have reported that peripheral stimulation of the
      innate immune system with lipopolysaccharide (LPS) causes an exaggerated
      neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice.
      Because LPS also causes depressive behavior, the purpose of this study was to
      determine whether aging is associated with an exacerbated depressive-like
      response. We confirmed that LPS (0.33 mg/kg intraperitoneal) induced a protracted
      sickness response in aged mice with reductions in locomotor and feeding
      activities 24 and 48 h postinjection, when young adults had fully recovered. When
      submitted to the forced swim test 24 h post-LPS, both young adult and aged mice
      exhibited an increased duration of immobility. However, when submitted to either
      the forced swim test or the tail suspension test 72 h post-LPS, an increased
      duration of immobility was evident only in aged mice. This prolonged depressive
      like behavior in aged LPS-treated mice was associated with a more pronounced
      induction of peripheral and brain indoleamine 2,3-dioxygenase and a markedly
      higher turnover rate of brain serotonin (as measured by the ratio of 5-hydroxy
      indoleacetic acid over 5-hydroxy-tryptamine) compared to young adult mice at 24
      post-LPS injection. These results provide the first evidence that age-associated
      reactivity of the brain cytokine system could play a pathophysiological role in
      the increased prevalence of depression observed in the elderly.

PMID- 18075494
TI  - Infantile nephropathic cystinosis.

PMID- 18075495
TI  - Semaphorin3a disrupts podocyte foot processes causing acute proteinuria.
AB  - Semaphorin3a was discovered as a secreted guidance protein that acts as a
      chemorepellent to migrating axons and endothelial cells. In the adult mouse
      kidney, it is expressed in podocytes and collecting tubules. Here, we show that
      exogenous semaphorin3a caused acute nephrotic range proteinuria associated with
      podocyte foot process effacement and fusion, endothelial cell damage, decreased
      vascular endothelial growth factor-A receptor expression, and downregulation of
      the slit-diaphragm proteins podocin, nephrin, and CD2-associated protein. When
      vascular endothelial growth factor 165 was administered at the same time as
      Semaphorin3a, no proteinuria or renal ultrastructural abnormalities occurred,
      suggesting that semaphorin3a effects may be mediated, in part, by downregulation
      of vascular endothelial growth factor receptor 2 signaling. Our findings indicate
      that a balance of semaphorin3a to vascular endothelial growth factor-A may be
      important for glomerular filtration barrier homeostasis.

PMID- 18075496
TI  - Overexpression of connective tissue growth factor in podocytes worsens diabetic
      nephropathy in mice.
AB  - Connective tissue growth factor (CTGF) is a potent inducer of extracellular
      matrix accumulation. In diabetic nephropathy, CTGF expression is markedly
      upregulated both in podocytes and mesangial cells, and this may play an important
      role in its pathogenesis. We established podocyte-specific CTGF-transgenic mice,
      which were indistinguishable at baseline from their wild-type littermates. Twelve
      weeks after streptozotocin-induced diabetes, these transgenic mice showed a more
      severe proteinuria, mesangial expansion, and a decrease in matrix
      metalloproteinase-2 activity compared to diabetic wild-type mice. Furthermore,
      diabetic transgenic mice exhibited less podocin expression and a decreased number
      of diffusely vacuolated podocytes compared to diabetic wild-type mice.
      Importantly, induction of diabetes in CTGF-transgenic mice resulted in a further
      elevation of endogenous CTGF mRNA expression and protein in the glomerular
      mesangium. Our findings suggest that overexpression of CTGF in podocytes is
      sufficient to exacerbate proteinuria and mesangial expansion through a functional
      impairment and loss of podocytes.

PMID- 18075497
TI  - Function of connexins in the renal circulation.
AB  - Connexins form intercellular channels that span two plasma membranes and directly
      couple the cytoplasm of adjacent cells. This morphological contact enables the
      exchange of ions, second messengers, and metabolites, which act to regulate
      several biological functions. This review focuses on the significance of
      connexins in the renal circulation. Cells of the renal vasculature are coupled
      and express connexins in a vessel and cell-specific pattern. This finding
      indicates that renal connexins likely play an important role in renal
      autoregulatory mechanisms (Bayliss effect, tubuloglomerular feedback) and in the
      control of vasomotor responses. The described coupling of endothelial and
      vascular smooth muscle cells in the afferent arterioles may also contribute to
      the communication of neighboring nephrons, called 'nephron coupling.'
      Furthermore, deletion of the Cx40 and Cx43 genes results in an altered functional
      behavior of the renin-producing cells, suggesting involvement of these connexin
      isoforms in the regulation of renin secretion and synthesis. In addition, this
      review discusses the role of renal connexin expression in the pathogenesis of
      hypertension or diabetes.

PMID- 18075498
TI  - Y-box protein-1 controls transforming growth factor-beta1 translation in proximal
      tubular cells.
AB  - Transforming growth factor-beta1 (TGF-beta1) mRNA has low basal translational
      efficiency in proximal tubule cells; however, its translation is stimulated by
      profibrotic cytokines. We studied the role of the multifunctional Y-box protein-1
      (YB-1) in regulating proximal tubule cell TGF-beta1 translation. Using RNA
      electrophoretic mobility shift assays and ultraviolet crosslinking, we found two
      protein complexes of 50 and 100 kDa, which bound to the TGF-beta1 mRNA 5'
      untranslated region. Supershift studies using antibodies to YB-1 showed that both
      sites contained YB-1 as did studies with recombinant YB-1, which demonstrated
      that it was sufficient to form both complexes. RNA competition experiments
      confirmed YB-1 binding to the two predicted binding sites; one with high affinity
      and the other with lower affinity. Strong basal YB-1 association with TGF-beta1
      mRNA was found in proximal tubule cells, which decreased when platelet-derived
      growth factor was used to activate TGF-beta1 translation. In contrast, knockdown
      of proximal tubule cell YB-1 expression abrogated TGF-beta1 synthesis. Our
      results suggest that TGF-beta1 translation in proximal tubule cells requires YB-1
      binding to a high-affinity site in the 5'-untranslated region of its mRNA;
      however, binding to a low-affinity site inhibits basal translation.

PMID- 18075499
TI  - Angiotensin mediates renal fibrosis in the nephropathy of glycogen storage
      disease type Ia.
AB  - Patients with glycogen storage disease type Ia (GSD-Ia) develop renal disease of
      unknown etiology despite intensive dietary therapies. This renal disease shares
      many clinical and pathological similarities to diabetic nephropathy. We studied
      the expression of angiotensinogen, angiotensin type 1 receptor, transforming
      growth factor-beta1, and connective tissue growth factor in mice with GSD-Ia and
      found them to be elevated compared to controls. While increased renal expression
      of angiotensinogen was evident in 2-week-old mice with GSD-Ia, the renal
      expression of transforming growth factor-beta and connective tissue growth factor
      did not increase for another week; consistent with upregulation of these factors
      by angiotensin II. The expression of fibronectin and collagens I, III, and IV was
      also elevated in the kidneys of mice with GSD-Ia, compared to controls. Renal
      fibrosis was characterized by a marked increase in the synthesis and deposition
      of extracellular matrix proteins in the renal cortex and histological
      abnormalities including tubular basement membrane thickening, tubular atrophy,
      tubular dilation, and multifocal interstitial fibrosis. Our results suggest that
      activation of the angiotensin system has an important role in the pathophysiology
      of renal disease in patients with GSD-Ia.

PMID- 18075500
TI  - Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor
      kinases, decreases renal fibrosis.
AB  - Progressive kidney fibrosis precedes end-stage renal failure in up to a third of
      patients with diabetes mellitus. Elevated intra-renal transforming growth factor
      beta (TGF-beta) is thought to underlie disease progression by promoting
      deposition of extracellular matrix and epithelial-mesenchymal transition.
      GW788388 is a new TGF-beta type I receptor inhibitor with a much improved
      pharmacokinetic profile compared with SB431542. We studied its effect in vitro
      and found that it inhibited both the TGF-beta type I and type II receptor kinase
      activities, but not that of the related bone morphogenic protein type II
      receptor. Further, it blocked TGF-beta-induced Smad activation and target gene
      expression, while decreasing epithelial-mesenchymal transitions and fibrogenesis.
      Using db/db mice, which develop diabetic nephropathy, we found that GW788388
      given orally for 5 weeks significantly reduced renal fibrosis and decreased the
      mRNA levels of key mediators of extracellular matrix deposition in kidneys. Our
      study shows that GW788388 is a potent and selective inhibitor of TGF-beta
      signalling in vitro and renal fibrosis in vivo.

PMID- 18075501
TI  - Non-traditional risk factors predict coronary calcification in chronic kidney
      disease in a population-based cohort.
AB  - The increased burden of cardiovascular disease in chronic kidney disease cannot
      be explained by traditional risk factors alone. Here, we evaluated the impact of
      non-traditional factors on the association of chronic kidney disease with
      coronary artery calcification using logistic regression among 2672 Dallas Heart
      Study patients of whom 220 had chronic kidney disease. The prevalence of coronary
      calcification significantly increased across all chronic kidney disease stages
      and this remained independently associated with coronary calcification after
      adjusting for traditional factors. The calcium x phosphorus product,
      homocysteine, and osteoprotegerin each diminished the magnitude of association
      between kidney disease and coronary calcification. After adjustment for these,
      the association between kidney disease and coronary calcification was no longer
      significant with the effects most prominent in the stages 3-5 subgroup. Our study
      has identified three non-traditional independent predictors of coronary
      calcification that diminished the association between chronic kidney disease and
      coronary calcification. These factors may represent novel mechanistic links
      warranting further investigation.

PMID- 18075502
TI  - Inhibition of NF-kappaB-dependent Bcl-xL expression by clusterin promotes albumin
      induced tubular cell apoptosis.
AB  - Apoptosis and inflammation, important contributors to the progression of chronic
      kidney disease, can be influenced by clusterin (a secreted glycoprotein that
      regulates apoptosis) and nuclear factor-kappaB (NF-kappaB, a transcription factor
      modifying the expression of inflammatory genes). We studied proteinuria-induced
      renal disease and its influence on clusterin-mediated apoptosis. Exposure of
      cultured mouse proximal tubule epithelial cells to bovine serum albumin (BSA)
      resulted in activation of NF-kappaB and activator protein-1 (AP-1) within hours
      followed by a decline in their activation, decreased activation of extracellular
      signal-regulated kinases (ERK1/2), decreased cell-associated antiapoptotic Bcl-xL
      protein but increased apoptosis. Clusterin progressively increased in the media
      over a 3 day period. Clusterin siRNA blocked protein production, increased NF
      kappaB activation, and significantly increased cellular Bcl-xL protein, thereby
      reducing spontaneous and BSA-induced apoptosis. An siRNA to the NF-kappaB
      inhibitor IkappaBalpha had similar results. BSA-stimulated NF-kappaB activation
      reciprocally decreased AP-1 activity by preventing ERK1/2 phosphorylation. These
      in vitro studies suggest that clusterin inhibits NF-kappaB-mediated antiapoptotic
      effects by the apparent stabilization of IkappaBalpha switching from promoting
      inflammation to apoptosis during proteinuria.

PMID- 18075503
TI  - Crude-oil biodegradation via methanogenesis in subsurface petroleum reservoirs.
AB  - Biodegradation of crude oil in subsurface petroleum reservoirs has adversely
      affected the majority of the world's oil, making recovery and refining of that
      oil more costly. The prevalent occurrence of biodegradation in shallow subsurface
      petroleum reservoirs has been attributed to aerobic bacterial hydrocarbon
      degradation stimulated by surface recharge of oxygen-bearing meteoric waters.
      This hypothesis is empirically supported by the likelihood of encountering
      biodegraded oils at higher levels of degradation in reservoirs near the surface.
      More recent findings, however, suggest that anaerobic degradation processes
      dominate subsurface sedimentary environments, despite slow reaction kinetics and
      uncertainty as to the actual degradation pathways occurring in oil reservoirs.
      Here we use laboratory experiments in microcosms monitoring the hydrocarbon
      composition of degraded oils and generated gases, together with the carbon
      isotopic compositions of gas and oil samples taken at wellheads and a Rayleigh
      isotope fractionation box model, to elucidate the probable mechanisms of
      hydrocarbon degradation in reservoirs. We find that crude-oil hydrocarbon
      degradation under methanogenic conditions in the laboratory mimics the
      characteristic sequential removal of compound classes seen in reservoir-degraded
      petroleum. The initial preferential removal of n-alkanes generates close to
      stoichiometric amounts of methane, principally by hydrogenotrophic
      methanogenesis. Our data imply a common methanogenic biodegradation mechanism in
      subsurface degraded oil reservoirs, resulting in consistent patterns of
      hydrocarbon alteration, and the common association of dry gas with severely
      degraded oils observed worldwide. Energy recovery from oilfields in the form of
      methane, based on accelerating natural methanogenic biodegradation, may offer a
      route to economic production of difficult-to-recover energy from oilfields.

PMID- 18075504
TI  - Popper revisited: GWAS here, last year.

PMID- 18075505
TI  - Diagnostic dilemma's: the congenital disorders of glycosylation are clinical
      chameleons.

PMID- 18075506
TI  - Daily use of phosphodiesterase 5 inhibitors for erectile dysfunction and lower
      urinary tract symptoms.
AB  - Erectile dysfunction is a prevalent disorder that not only affects men with the
      disorder but also their partners. Significant improvements in the sexual health
      of these couples have been achieved with the introduction of phosphodiesterase 5
      (PDE5) inhibitors. Currently PDE5 inhibitors are used on an on-demand basis. New
      evidence regarding the effects of PDE5 inhibitors on the underlying
      pathophysiologic processes that cause erectile dysfunction have sparked interest
      in the continuous dosing of these medications. We will discuss the biological
      background and the available clinical evidence for the continuous use of
      phosphodiesterase inhibitors in erectile dysfunction. Lastly, we will discuss the
      emerging clinical data for the use of daily PDE5 inhibitors in men with lower
      urinary tract symptoms.

PMID- 18075507
TI  - The engineering analysis of bioheat equation and penile hemodynamic relationships
      in the diagnosis of erectile dysfunction: part I-theoretical study and
      mathematical modeling.
AB  - The extent to which skin surface bioheat perfusion predicts penile physiological
      response such as an erection has not been extensively investigated. A
      biomechanical engineering study was performed to compare bioheat distribution on
      penile skin surface resulting from an induced erection at steady state to examine
      the efficacy of such method as an adjunct tool for the diagnosis and
      classification of erectile dysfunction (ED) due to different etiology. We based
      our arguments on the principle that blood vessel activity and perfusion to corpus
      cavernosa at the erect state are almost always higher than that in the flaccid
      state. Our results showed that a difference of 0.1-0.3 degrees C can be observed
      and hence used to develop database of 'smart diagnosis' for ED using the machine
      artificial intelligence. It is anticipated that such basic research into blood
      flow is critical, as blood perfusion into corpus cavernosa is the most
      influential factor determining functional erectile quality contributing to
      successful coitus. Increased understanding of the hemodynamic response profile
      contributes toward optimal treatment and thus enables clinicians to adopt an
      appropriate management scheme for ED.

PMID- 18075508
TI  - The engineering analysis of bioheat equation and penile hemodynamic relationships
      in the diagnosis of erectile dysfunction: part II-model optimization using the
      ANOVA and Taguchi method.
AB  - The authors aimed to study the skin surface bioheat perfusion model described in
      part I numerically. The influence of each constituent in the determination of
      surface temperature profile was statistically examined. The theoretically derived
      data will then be benchmarked with clinically measured data to develop the
      artificial intelligence system for the diagnosis of erectile dysfunction (ED).
      The new approach is based on the hypothesis that there exists a constitutive
      relationship between surface temperature profiles and the etiology of ED. By
      considering the penis model as a group of reservoirs with irregular cavities, we
      built a numerical model, simplified to save computational costs while still
      realistically able to represent the actual for partial differential calculation.
      Incompressible blood flow was assumed coupled with the classical bioheat transfer
      equation which was solved using the finite element method. Isotropic homogeneous
      heat diffusivity was assigned to each tissue layer. The results of simulations
      were tested for sensitivity analysis and further optimized to obtain the 'best'
      signal from the simulations using the Taguchi method. Four important parameters
      were identified and analysis of variance was performed using the 2(n) design
      (n=number of parameters, in this case, 4). The implications of these parameters
      were hypothesized based on physiological observations. Our results show that for
      an optimum signal-to-noise (S/N) ratio, the noise factors (thermal conductivity
      of skin, A and tunica albuginea, B) must be set high and low, respectively.
      Hence, at this setting, the signal will be captured based on the perfusion rate
      of the boundary layer of the sinusoidal space and the blood pressure (perfusion
      of sinusoidal space, C and blood pressure, D) will be optimal as their S/N ratios
      (C (low) and D (low)) are larger than the former.

PMID- 18075509
TI  - Ethical problems with bioidentical hormone therapy.
AB  - The term 'bioidentical' hormone replacement therapy (BHRT) is widely
      misunderstood by the patient population and misrepresented in patient literature.
      Within the clinical community, BHRT is currently being prescribed by some as an
      'innovative therapy' with no published evidence in peer-reviewed journals that it
      is better than the current standard of care; in at least one case, BHRT is being
      used as a study agent in unregulated and unethical research involving very high
      doses of estrogen and progesterone. Additionally, professional ethics problems
      abound within the prescribing population, since those claiming expertise and
      training in BHRT vary widely in competencies, may cross practice boundaries, and
      may have overt conflicts of interest if they are selling or promoting their own
      for-profit recipes of BHRT on commercial forums. Ultimately, BHRT presents
      clinical, research and professional ethics problems that are discussed in depth.

PMID- 18075510
TI  - Measuring developmentally appropriate practice in neonatal intensive care units.
AB  - OBJECTIVE: Neonatal intensive care units (NICUs) impose stressors on development.
      Comparative studies have focused mostly on the units' medical qualities and less
      on their developmental 'ecology'. The aim of the study was to develop a tool for
      measuring the various domains of a developmentally appropriate practice in the
      NICU environment, and to assess its implementation in Israel. STUDY DESIGN: A
      questionnaire, designed for NICU senior staff members, was completed by 76
      respondents representing 24 NICUs in Israel. The tool that measures
      developmentally appropriate practice as applied in the NICU environment includes
      the following three domains: (a) parental and family involvement, (b)
      environmental control and (c) individualized care and assessment. These measures
      jointly produce the developmentally appropriate neonatal intensive-care practice
      (DANIP) index. RESULT: High variability was found in the application of
      procedures and programs considered developmentally appropriate. Units with a
      relatively large multidisciplinary team scored high. Overall, the NICUs in Israel
      did not consistently follow an integrated form of the developmental care as
      provided by the Neonatal Individualized Developmental Care and Assessment
      Program. It was found that individualized care and assessment was significantly
      and positively linked to control of the environment (r=0.53, P<0.01) and to
      parental and family involvement (r=0.76, P<0.01); the latter two scales were not
      associated. Of the three DANIP domains, parental involvement was salient.
      Although the staff highly appreciated the importance of environmental control and
      individualized care, application was limited. CONCLUSION: The DANIP index
      provides a good starting point for comparative studies.

PMID- 18075511
TI  - Global notes: how many babies were ever born in the world? What is the hope for
      future?

PMID- 18075512
TI  - Survivin, cancer networks and pathway-directed drug discovery.
AB  - Although there is no shortage of potential targets for cancer therapeutics, we
      know of only a handful of molecules that are differentially expressed in cancer
      and intersect multiple pathways required for tumour maintenance. Survivin
      embodies these properties, and orchestrates integrated cellular networks that are
      essential for tumour cell proliferation and viability. Pursuing the nodal
      functions of survivin in cancer might lead to the development of global pathway
      inhibitors with unique therapeutic potential.

PMID- 18075513
TI  - Variants in the 5q31 cytokine gene cluster are associated with psoriasis.
AB  - A multitiered genetic association study of 25 215 single-nucleotide polymorphisms
      (SNPs) in three case-control sample sets (1446 patients and 1432 controls)
      identified three IL13-linked SNPs (rs1800925, rs20541 and rs848) associated with
      psoriasis. Although the susceptibility effects at these SNPs were modest (joint
      allelic odds ratios (ORs): 0.76 to 0.78; P(comb): 1.3E-03 to 2.50E-04), the
      association patterns were consistent across the sample sets, with the minor
      alleles being protective. Haplotype analyses identified one common, susceptible
      haplotype CCG (joint allelic OR=1.27; P(comb)=1.88E-04) and a less common,
      protective haplotype TTT (joint allelic OR=0.74; P(comb)=7.05E-04). In
      combination with the other known genetic risk factors, HLA-C, IL12B and IL23R,
      the variants reported here generate an 11-fold psoriasis-risk differential.
      Residing in the 5q31 cytokine gene cluster, IL13 encodes an important T-cell
      derived cytokine that regulates cell-mediated immunity. These results provide the
      foundation for additional studies required to fully dissect the associations
      within this cytokine-rich genomic region, as polymorphisms in closely linked
      candidate genes, such as IRF1, IL5 or IL4, may be driving these results through
      linkage disequilibrium.

PMID- 18075514
TI  - Genetic control of susceptibility to pulmonary infection with Chlamydia
      pneumoniae in the mouse.
AB  - A mouse model was used to study the genetic control of differential host response
      to pulmonary infection with Chlamydia pneumoniae. The A/J and C57BL/6 strains
      show differential response to intranasal infection with respect to their ability
      to clear pulmonary bacterial load and the extent of lung pathology developed by 2
      weeks post infection. The genetic basis of this interstrain difference was
      studied by whole-genome scan in an informative [A/J x C57BL/6J] F2 cross using
      the pulmonary microbial load as a phenotypic readout of host response. We
      detected a highly significant linkage (LOD score=11.5) on chromosome 17 that
      overlaps with the major histocompatibility (MHC) locus. This quantitative trait
      locus (QTL) accounts for approximately 30% of the phenotypic variance with B6
      alleles conferring susceptibility and inherited in a recessive fashion.
      Significant linkage was also detected to chromosome 5 in female mice, while
      chromosome 6 showed suggestive linkage in male mice, pointing to additional
      complexity in the genetic control of the difference in susceptibility observed in
      A/J and C57BL/6J.

PMID- 18075515
TI  - ES cells derived from cloned embryos in monkey--a jump toward human therapeutic
      cloning.

PMID- 18075516
TI  - Kinases meet at TSC.

PMID- 18075517
TI  - RIG-I has guts: identification of a role for RIG-I in colitis development.

PMID- 18075518
TI  - Predictive value of von Willebrand factor for adverse clinical outcome in
      hypertensive patients with mild-to-moderate aortic regurgitation.
AB  - Plasma levels of von Willebrand factor (vWF), a marker of endothelial
      dysfunction/damage, are elevated in high-risk hypertensive patients and in
      patients with severe aortic regurgitation (AR). Patients with mild-to-moderate
      AR, frequently detected in hypertensive elderly, have additional left ventricular
      morphological and functional dysfunctions. We hypothesized that hypertensive
      patients with mild-to-moderate AR may have enhanced endothelial and/or left
      ventricular dysfunctions that may lead to a deteriorated prognosis. We measured
      vWF, prothrombin F1+2 (F 1+2) as a marker of thrombin generation, brain
      natriuretic peptide (BNP) in 104 hypertensive patients with mild-to-moderate AR
      and 66 hypertensive patients without AR. The left ventricular diameter at systole
      (LVDs) and left ventricular posterior wall thickness (LVWT) were determined by
      echocardiography and indexed by body surface area (LVDs/BSA and LVWT/BSA). VWF
      (median, interquartile range (IQR) 154, 120-196%) and BNP (34.7 pg ml(-1), 15
      65%) levels were greater in patients with AR than in those without AR (135, 98
      175% and 20, 10.3-49 pg ml(-1)). All patients were prospectively followed up for
      cardiac events during the period of median 43 months (IQR 31-81). Patients with
      AR had an increased risk of cardiac events (regression ratio (RR) 1.87, 95%
      confidence interval 1.28-2.87) when compared to those without AR. A multivariate
      Cox hazard analysis indicated that log vWF (RR 4.93) and log BNP (RR 1.9) were
      independent predictors in patients with AR. VWF was an independent predictor of
      clinical outcome in hypertensive patients with mild-to-moderate AR.

PMID- 18075520
TI  - Increased ET(A) and ET(B) receptor contraction in the left internal mammary
      artery from patients with hypertension.

PMID- 18075519
TI  - Structural and functional arterial properties in patients with obstructive sleep
      apnoea syndrome and cardiovascular comorbidities.
AB  - The increased severity of obstructive sleep apnoea syndrome (OSAS) is associated
      with a parallel increase in the incidence of cardiovascular events. Whether the
      increased severity of OSAS is in fact associated with impaired arterial
      properties has never been thoroughly studied. In patients with OSAS who carry a
      high burden of cardiovascular risk factors, we investigated whether the severity
      of OSAS is associated with deterioration in the arterial properties, independent
      of classical cardiovascular risk factors. In 74 consecutive patients with OSAS,
      we non-invasively assessed, by means of tonometry and high-resolution ultrasound:
      carotid intima-media thickness (IMT), carotid diameter and plaques, carotid
      femoral pulse wave velocity (PWV), central augmentation index (AI) and central
      blood pressures. The respiratory disturbance index was an independent predictor
      of IMT and PWV but not of carotid plaques, carotid diameter, AI or central blood
      pressures. Several parameters of nocturnal hypoxaemia were independently
      correlated with carotid IMT and PWV. In conclusion, arterial stiffening and
      thickening are modulated by the severity of OSAS, independently from age and
      cardiovascular risk factors.

PMID- 18075521
TI  - Berberine-induced mobilization of circulating endothelial progenitor cells
      improves human small artery elasticity.
AB  - Berberine (BR) has been proved to promote endothelial function. However, the
      exact mechanisms underlying the effect of BR on endothelial function are not
      completely clear. It has been demonstrated that endothelial progenitor cells
      (EPCs) contribute to improvement of endothelial function and C2 small artery
      elasticity index is a surrogate parameter for the clinical evaluation of
      endothelial function. We hypothesized that BR-induced mobilization of circulating
      EPCs is associated with BR-related improvement of endothelial function. To
      address this assumption, 15 healthy volunteers were recruited and received BR 0.4
      g three times per day for 30 days. The number of circulating CD34/KDR double
      positive cells as well as C1 large and C2 small artery elasticity indices were
      evaluated before and after BR therapy. The number of CD34/KDR double-positive
      EPCs increased significantly after BR treatment (0.030+/-0.020% vs 0.017+/
      0.010%, P<0.01). After 30-day BR therapy C2 increased significantly (6.21+/-2.80
      ml per mm Hg x 100 vs 4.06+/-2.67 ml per mm Hg x 100, P<0.01) and C1 remained
      unchanged (10.79+/-3.27 ml per mm Hg x 10 vs 10.06+/-2.08 ml per mm Hg x 10,
      P>0.05). The increment of CD34/KDR double-positive EPCs was positively correlated
      with the increment of C2 (r=0.68, P<0.01). We concluded that BR-induced
      mobilization of circulating EPCs contributes to improvement of small artery
      elasticity in healthy persons.

PMID- 18075522
TI  - Kimberlite ascent and eruption.
AB  - Wilson and Head model kimberlite ascent and eruption by considering the
      propagation of a volatile-rich dyke. Wilson and Head's model has features in
      common with Sparks et al., but it is inconsistent with geological observations
      and constraints on volatile solubility. Here we show that this may be due to
      erroneous physical assumptions.

PMID- 18075527
TI  - Hollow victory.

PMID- 18075528
TI  - Directive action required.

PMID- 18075529
TI  - Venezuela's way ahead.

PMID- 18075532
TI  - Nuclear-reactor closure hits cancer tests.

PMID- 18075533
TI  - London to host ambitious research hub.

PMID- 18075534
TI  - Enigmatic clouds illuminated.

PMID- 18075535
TI  - Showdown for Europe.

PMID- 18075545
TI  - Promise boiling over.

PMID- 18075550
TI  - Gardening: a garden for all climates.

PMID- 18075551
TI  - Archaeology: pieces of the puzzle.

PMID- 18075552
TI  - Abnormal neuroscience: Scanning psychopaths.

PMID- 18075553
TI  - Educational success must start in Pakistan's schools.

PMID- 18075554
TI  - Motivation needed to cure lifestyle diseases.

PMID- 18075555
TI  - Debate over flood-proofing effects of planting forests.

PMID- 18075556
TI  - All fishing nations must unite to cut subsidies.

PMID- 18075565
TI  - Photonics: rogue waves surface in light.

PMID- 18075567
TI  - Malaria: differential parasite drive.

PMID- 18075568
TI  - Astronomy: dim view of past clashes.

PMID- 18075569
TI  - Structural biology: ion pumps made crystal clear.

PMID- 18075570
TI  - Molecular biology: genome under surveillance.

PMID- 18075571
TI  - Materials chemistry: cool conditions for mobile ions.

PMID- 18075573
TI  - Obituary: Gene H. Golub (1932-2007).

PMID- 18075575
TI  - Dynamic personalities of proteins.
AB  - Because proteins are central to cellular function, researchers have sought to
      uncover the secrets of how these complex macromolecules execute such a
      fascinating variety of functions. Although static structures are known for many
      proteins, the functions of proteins are governed ultimately by their dynamic
      character (or 'personality'). The dream is to 'watch' proteins in action in real
      time at atomic resolution. This requires addition of a fourth dimension, time, to
      structural biology so that the positions in space and time of all atoms in a
      protein can be described in detail.

PMID- 18075576
TI  - The molecular sociology of the cell.
AB  - Proteomic studies have yielded detailed lists of the proteins present in a cell.
      Comparatively little is known, however, about how these proteins interact and are
      spatially arranged within the 'functional modules' of the cell: that is, the
      'molecular sociology' of the cell. This gap is now being bridged by using
      emerging experimental techniques, such as mass spectrometry of complexes and
      single-particle cryo-electron microscopy, to complement traditional biochemical
      and biophysical methods. With the development of integrative computational
      methods to exploit the data obtained, such hybrid approaches will uncover the
      molecular architectures, and perhaps even atomic models, of many protein
      complexes. With these structures in hand, researchers will be poised to use cryo
      electron tomography to view protein complexes in action within cells, providing
      unprecedented insights into protein-interaction networks.

PMID- 18075577
TI  - The origin of protein interactions and allostery in colocalization.
AB  - Two fundamental principles can account for how regulated networks of interacting
      proteins originated in cells. These are the law of mass action, which holds that
      the binding of one molecule to another increases with concentration, and the fact
      that the colocalization of molecules vastly increases their local concentrations.
      It follows that colocalization can amplify the effect on one protein of random
      mutations in another protein and can therefore, through natural selection, lead
      to interactions between proteins and to a startling variety of complex allosteric
      controls. It also follows that allostery is common and that homologous proteins
      can have different allosteric mechanisms. Thus, the regulated protein networks of
      organisms seem to be the inevitable consequence of natural selection operating
      under physical laws.

PMID- 18075578
TI  - The biological impact of mass-spectrometry-based proteomics.
AB  - In the past decade, there have been remarkable advances in proteomic
      technologies. Mass spectrometry has emerged as the preferred method for in-depth
      characterization of the protein components of biological systems. Using mass
      spectrometry, key insights into the composition, regulation and function of
      molecular complexes and pathways have been gained. From these studies, it is
      clear that mass-spectrometry-based proteomics is now a powerful 'hypothesis
      generating engine' that, when combined with complementary molecular, cellular and
      pharmacological techniques, provides a framework for translating large data sets
      into an understanding of complex biological processes.

PMID- 18075579
TI  - Reaching for high-hanging fruit in drug discovery at protein-protein interfaces.
AB  - Targeting the interfaces between proteins has huge therapeutic potential, but
      discovering small-molecule drugs that disrupt protein-protein interactions is an
      enormous challenge. Several recent success stories, however, indicate that
      protein-protein interfaces might be more tractable than has been thought. These
      studies discovered small molecules that bind with drug-like potencies to
      'hotspots' on the contact surfaces involved in protein-protein interactions.
      Remarkably, these small molecules bind deeper within the contact surface of the
      target protein, and bind with much higher efficiencies, than do the contact atoms
      of the natural protein partner. Some of these small molecules are now making
      their way through clinical trials, so this high-hanging fruit might not be far
      out of reach.

PMID- 18075580
TI  - Transformation and diversification in early mammal evolution.
AB  - Evolution of the earliest mammals shows successive episodes of diversification.
      Lineage-splitting in Mesozoic mammals is coupled with many independent
      evolutionary experiments and ecological specializations. Classic scenarios of
      mammalian morphological evolution tend to posit an orderly acquisition of key
      evolutionary innovations leading to adaptive diversification, but newly
      discovered fossils show that evolution of such key characters as the middle ear
      and the tribosphenic teeth is far more labile among Mesozoic mammals. Successive
      diversifications of Mesozoic mammal groups multiplied the opportunities for many
      dead-end lineages to iteratively evolve developmental homoplasies and convergent
      ecological specializations, parallel to those in modern mammal groups.

PMID- 18075581
TI  - Two stellar components in the halo of the Milky Way.
AB  - The halo of the Milky Way provides unique elemental abundance and kinematic
      information on the first objects to form in the Universe, and this information
      can be used to tightly constrain models of galaxy formation and evolution.
      Although the halo was once considered a single component, evidence for its
      dichotomy has slowly emerged in recent years from inspection of small samples of
      halo objects. Here we show that the halo is indeed clearly divisible into two
      broadly overlapping structural components--an inner and an outer halo--that
      exhibit different spatial density profiles, stellar orbits and stellar
      metallicities (abundances of elements heavier than helium). The inner halo has a
      modest net prograde rotation, whereas the outer halo exhibits a net retrograde
      rotation and a peak metallicity one-third that of the inner halo. These
      properties indicate that the individual halo components probably formed in
      fundamentally different ways, through successive dissipational (inner) and
      dissipationless (outer) mergers and tidal disruption of proto-Galactic clumps.

PMID- 18075582
TI  - Molecular code for transmembrane-helix recognition by the Sec61 translocon.
AB  - Transmembrane alpha-helices in integral membrane proteins are recognized co
      translationally and inserted into the membrane of the endoplasmic reticulum by
      the Sec61 translocon. A full quantitative description of this phenomenon, linking
      amino acid sequence to membrane insertion efficiency, is still lacking. Here,
      using in vitro translation of a model protein in the presence of dog pancreas
      rough microsomes to analyse a large number of systematically designed hydrophobic
      segments, we present a quantitative analysis of the position-dependent
      contribution of all 20 amino acids to membrane insertion efficiency, as well as
      of the effects of transmembrane segment length and flanking amino acids. The
      emerging picture of translocon-mediated transmembrane helix assembly is simple,
      with the critical sequence characteristics mirroring the physical properties of
      the lipid bilayer.

PMID- 18075583
TI  - Chromatin remodelling at promoters suppresses antisense transcription.
AB  - Chromatin allows the eukaryotic cell to package its DNA efficiently. To
      understand how chromatin structure is controlled across the Saccharomyces
      cerevisiae genome, we have investigated the role of the ATP-dependent chromatin
      remodelling complex Isw2 in positioning nucleosomes. We find that Isw2 functions
      adjacent to promoter regions where it repositions nucleosomes at the interface
      between genic and intergenic sequences. Nucleosome repositioning by Isw2 is
      directional and results in increased nucleosome occupancy of the intergenic
      region. Loss of Isw2 activity leads to inappropriate transcription, resulting in
      the generation of both coding and noncoding transcripts. Here we show that Isw2
      repositions nucleosomes to enforce directionality on transcription by preventing
      transcription initiation from cryptic sites. Our analyses reveal how chromatin is
      organized on a global scale and advance our understanding of how transcription is
      regulated.

PMID- 18075584
TI  - The structural basis of calcium transport by the calcium pump.
AB  - The sarcoplasmic reticulum Ca2+-ATPase, a P-type ATPase, has a critical role in
      muscle function and metabolism. Here we present functional studies and three new
      crystal structures of the rabbit skeletal muscle Ca2+-ATPase, representing the
      phosphoenzyme intermediates associated with Ca2+ binding, Ca2+ translocation and
      dephosphorylation, that are based on complexes with a functional ATP analogue,
      beryllium fluoride and aluminium fluoride, respectively. The structures complete
      the cycle of nucleotide binding and cation transport of Ca2+-ATPase.
      Phosphorylation of the enzyme triggers the onset of a conformational change that
      leads to the opening of a luminal exit pathway defined by the transmembrane
      segments M1 through M6, which represent the canonical membrane domain of P-type
      pumps. Ca2+ release is promoted by translocation of the M4 helix, exposing Glu
      309, Glu 771 and Asn 796 to the lumen. The mechanism explains how P-type ATPases
      are able to form the steep electrochemical gradients required for key functions
      in eukaryotic cells.

PMID- 18075585
TI  - Crystal structure of the sodium-potassium pump.
AB  - The Na+,K+-ATPase generates electrochemical gradients for sodium and potassium
      that are vital to animal cells, exchanging three sodium ions for two potassium
      ions across the plasma membrane during each cycle of ATP hydrolysis. Here we
      present the X-ray crystal structure at 3.5 A resolution of the pig renal Na+,K+
      ATPase with two rubidium ions bound (as potassium congeners) in an occluded state
      in the transmembrane part of the alpha-subunit. Several of the residues forming
      the cavity for rubidium/potassium occlusion in the Na+,K+-ATPase are homologous
      to those binding calcium in the Ca2+-ATPase of sarco(endo)plasmic reticulum. The
      beta- and gamma-subunits specific to the Na+,K+-ATPase are associated with
      transmembrane helices alphaM7/alphaM10 and alphaM9, respectively. The gamma
      subunit corresponds to a fragment of the V-type ATPase c subunit. The carboxy
      terminus of the alpha-subunit is contained within a pocket between transmembrane
      helices and seems to be a novel regulatory element controlling sodium affinity,
      possibly influenced by the membrane potential.

PMID- 18075586
TI  - A dynamic, rotating ring current around Saturn.
AB  - The concept of an electrical current encircling the Earth at high altitudes was
      first proposed in 1917 to explain the depression of the horizontal component of
      the Earth's magnetic field during geomagnetic storms. In situ measurements of the
      extent and composition of this current were made some 50 years later and an image
      was obtained in 2001 (ref. 6). Ring currents of a different nature were observed
      at Jupiter and their presence inferred at Saturn. Here we report images of the
      ring current at Saturn, together with a day-night pressure asymmetry and tilt of
      the planet's plasma sheet, based on measurements using the magnetospheric imaging
      instrument (MIMI) on board Cassini. The ring current can be highly variable with
      strong longitudinal asymmetries that corotate nearly rigidly with the planet.
      This contrasts with the Earth's ring current, where there is no rotational
      modulation and initial asymmetries are organized by local time effects.

PMID- 18075587
TI  - Optical rogue waves.
AB  - Recent observations show that the probability of encountering an extremely large
      rogue wave in the open ocean is much larger than expected from ordinary wave
      amplitude statistics. Although considerable effort has been directed towards
      understanding the physics behind these mysterious and potentially destructive
      events, the complete picture remains uncertain. Furthermore, rogue waves have not
      yet been observed in other physical systems. Here, we introduce the concept of
      optical rogue waves, a counterpart of the infamous rare water waves. Using a new
      real-time detection technique, we study a system that exposes extremely steep,
      large waves as rare outcomes from an almost identically prepared initial
      population of waves. Specifically, we report the observation of rogue waves in an
      optical system, based on a microstructured optical fibre, near the threshold of
      soliton-fission supercontinuum generation--a noise-sensitive nonlinear process in
      which extremely broadband radiation is generated from a narrowband input. We
      model the generation of these rogue waves using the generalized nonlinear
      Schrodinger equation and demonstrate that they arise infrequently from initially
      smooth pulses owing to power transfer seeded by a small noise perturbation.

PMID- 18075588
TI  - A distinct bosonic mode in an electron-doped high-transition-temperature
      superconductor.
AB  - Despite recent advances in understanding high-transition-temperature (high-T(c))
      superconductors, there is no consensus on the origin of the superconducting
      'glue': that is, the mediator that binds electrons into superconducting pairs.
      The main contenders are lattice vibrations (phonons) and spin-excitations, with
      the additional possibility of pairing without mediators. In conventional
      superconductors, phonon-mediated pairing was unequivocally established by data
      from tunnelling experiments. Proponents of phonons as the high-T(c) glue were
      therefore encouraged by the recent scanning tunnelling microscopy experiments on
      hole-doped Bi2Sr2CaCu2O8-delta (BSCCO) that reveal an oxygen lattice vibrational
      mode whose energy is anticorrelated with the superconducting gap energy scale.
      Here we report high-resolution scanning tunnelling microscopy measurements of the
      electron-doped high-T(c) superconductor Pr0.88LaCe0.12CuO4 (PLCCO) (T(c) = 24 K)
      that reveal a bosonic excitation (mode) at energies of 10.5 +/- 2.5 meV. This
      energy is consistent with both spin-excitations in PLCCO measured by inelastic
      neutron scattering (resonance mode) and a low-energy acoustic phonon mode, but
      differs substantially from the oxygen vibrational mode identified in BSCCO. Our
      analysis of the variation of the local mode energy and intensity with the local
      gap energy scale indicates an electronic origin of the mode consistent with spin
      excitations rather than phonons.

PMID- 18075589
TI  - Infinite-layer iron oxide with a square-planar coordination.
AB  - Conventional high-temperature reactions limit the control of coordination
      polyhedra in transition-metal oxides to those obtainable within the bounds of
      known coordination geometries for a given transition metal. For example, iron
      atoms are almost exclusively coordinated by three-dimensional polyhedra such as
      tetrahedra and octahedra. However, recent works have shown that binary metal
      hydrides act as reducing agents at low temperatures, allowing access to
      unprecedented structures. Here we show the reaction of a perovskite SrFeO3 with
      CaH2 to yield SrFeO2, a new compound bearing a square-planar oxygen coordination
      around Fe2+. SrFeO2 is isostructural with 'infinite layer' cupric oxides, and
      exhibits a magnetic order far above room temperature in spite of the two
      dimensional structure, indicating strong in-layer magnetic interactions due to
      strong Fe d to O p hybridization. Surprisingly, SrFeO2 remains free from the
      structural instability that might well be expected at low temperatures owing to
      twofold orbital degeneracy in the Fe2+ ground state with D(4h) point symmetry.
      The reduction and the oxidation between SrFeO2 and SrFeO3 proceed via the
      brownmillerite-type intermediate SrFeO2.5, and start at the relatively low
      temperature of approximately 400 K, making the material appealing for a variety
      of applications, including oxygen ion conduction, oxygen gas absorption and
      catalysis.

PMID- 18075590
TI  - Effect of remote sea surface temperature change on tropical cyclone potential
      intensity.
AB  - The response of tropical cyclone activity to global warming is widely debated. It
      is often assumed that warmer sea surface temperatures provide a more favourable
      environment for the development and intensification of tropical cyclones, but
      cyclone genesis and intensity are also affected by the vertical thermodynamic
      properties of the atmosphere. Here we use climate models and observational
      reconstructions to explore the relationship between changes in sea surface
      temperature and tropical cyclone 'potential intensity'--a measure that provides
      an upper bound on cyclone intensity and can also reflect the likelihood of
      cyclone development. We find that changes in local sea surface temperature are
      inadequate for characterizing even the sign of changes in potential intensity,
      but that long-term changes in potential intensity are closely related to the
      regional structure of warming; regions that warm more than the tropical average
      are characterized by increased potential intensity, and vice versa. We use this
      relationship to reconstruct changes in potential intensity over the twentieth
      century from observational reconstructions of sea surface temperature. We find
      that, even though tropical Atlantic sea surface temperatures are currently at a
      historical high, Atlantic potential intensity probably peaked in the 1930s and
      1950s, and recent values are near the historical average. Our results indicate
      that--per unit local sea surface temperature change--the response of tropical
      cyclone activity to natural climate variations, which tend to involve localized
      changes in sea surface temperature, may be larger than the response to the more
      uniform patterns of greenhouse-gas-induced warming.

PMID- 18075591
TI  - Dynamics of Mid-Palaeocene North Atlantic rifting linked with European intra
      plate deformations.
AB  - The process of continental break-up provides a large-scale experiment that can be
      used to test causal relations between plate tectonics and the dynamics of the
      Earth's deep mantle. Detailed diagnostic information on the timing and dynamics
      of such events, which are not resolved by plate kinematic reconstructions, can be
      obtained from the response of the interior of adjacent continental plates to
      stress changes generated by plate boundary processes. Here we demonstrate a
      causal relationship between North Atlantic continental rifting at approximately
      62 Myr ago and an abrupt change of the intra-plate deformation style in the
      adjacent European continent. The rifting involved a left-lateral displacement
      between the North American-Greenland plate and Eurasia, which initiated the
      observed pause in the relative convergence of Europe and Africa. The associated
      stress change in the European continent was significant and explains the sudden
      termination of a approximately 20-Myr-long contractional intra-plate deformation
      within Europe, during the late Cretaceous period to the earliest Palaeocene
      epoch, which was replaced by low-amplitude intra-plate stress-relaxation
      features. The pre-rupture tectonic stress was large enough to have been
      responsible for precipitating continental break-up, so there is no need to invoke
      a thermal mantle plume as a driving mechanism. The model explains the
      simultaneous timing of several diverse geological events, and shows how the intra
      continental stratigraphic record can reveal the timing and dynamics of stress
      changes, which cannot be resolved by reconstructions based only on plate
      kinematics.

PMID- 18075592
TI  - Fetal load and the evolution of lumbar lordosis in bipedal hominins.
AB  - As predicted by Darwin, bipedal posture and locomotion are key distinguishing
      features of the earliest known hominins. Hominin axial skeletons show many
      derived adaptations for bipedalism, including an elongated lumbar region, both in
      the number of vertebrae and their lengths, as well as a marked posterior
      concavity of wedged lumbar vertebrae, known as a lordosis. The lordosis
      stabilizes the upper body over the lower limbs in bipeds by positioning the
      trunk's centre of mass (COM) above the hips. However, bipedalism poses a unique
      challenge to pregnant females because the changing body shape and the extra mass
      associated with pregnancy shift the trunk's COM anterior to the hips. Here we
      show that human females have evolved a derived curvature and reinforcement of the
      lumbar vertebrae to compensate for this bipedal obstetric load. Similarly
      dimorphic morphologies in fossil vertebrae of Australopithecus suggest that this
      adaptation to fetal load preceded the evolution of Homo.

PMID- 18075593
TI  - CLOCK-mediated acetylation of BMAL1 controls circadian function.
AB  - Regulation of circadian physiology relies on the interplay of interconnected
      transcriptional-translational feedback loops. The CLOCK-BMAL1 complex activates
      clock-controlled genes, including cryptochromes (Crys), the products of which act
      as repressors by interacting directly with CLOCK-BMAL1. We have demonstrated that
      CLOCK possesses intrinsic histone acetyltransferase activity and that this
      enzymatic function contributes to chromatin-remodelling events implicated in
      circadian control of gene expression. Here we show that CLOCK also acetylates a
      non-histone substrate: its own partner, BMAL1, is specifically acetylated on a
      unique, highly conserved Lys 537 residue. BMAL1 undergoes rhythmic acetylation in
      mouse liver, with a timing that parallels the downregulation of circadian
      transcription of clock-controlled genes. BMAL1 acetylation facilitates
      recruitment of CRY1 to CLOCK-BMAL1, thereby promoting transcriptional repression.
      Importantly, ectopic expression of a K537R-mutated BMAL1 is not able to rescue
      circadian rhythmicity in a cellular model of peripheral clock. These findings
      reveal that the enzymatic interplay between two clock core components is crucial
      for the circadian machinery.

PMID- 18075594
TI  - A viral microRNA functions as an orthologue of cellular miR-155.
AB  - All metazoan eukaryotes express microRNAs (miRNAs), roughly 22-nucleotide
      regulatory RNAs that can repress the expression of messenger RNAs bearing
      complementary sequences. Several DNA viruses also express miRNAs in infected
      cells, suggesting a role in viral replication and pathogenesis. Although specific
      viral miRNAs have been shown to autoregulate viral mRNAs or downregulate cellular
      mRNAs, the function of most viral miRNAs remains unknown. Here we report that the
      miR-K12-11 miRNA encoded by Kaposi's-sarcoma-associated herpes virus (KSHV) shows
      significant homology to cellular miR-155, including the entire miRNA 'seed'
      region. Using a range of assays, we show that expression of physiological levels
      of miR-K12-11 or miR-155 results in the downregulation of an extensive set of
      common mRNA targets, including genes with known roles in cell growth regulation.
      Our findings indicate that viral miR-K12-11 functions as an orthologue of
      cellular miR-155 and probably evolved to exploit a pre-existing gene regulatory
      pathway in B cells. Moreover, the known aetiological role of miR-155 in B-cell
      transformation suggests that miR-K12-11 may contribute to the induction of KSHV
      positive B-cell tumours in infected patients.

PMID- 18075595
TI  - Crystal structure of the plasma membrane proton pump.
AB  - A prerequisite for life is the ability to maintain electrochemical imbalances
      across biomembranes. In all eukaryotes the plasma membrane potential and
      secondary transport systems are energized by the activity of P-type ATPase
      membrane proteins: H+-ATPase (the proton pump) in plants and fungi, and Na+,K+
      ATPase (the sodium-potassium pump) in animals. The name P-type derives from the
      fact that these proteins exploit a phosphorylated reaction cycle intermediate of
      ATP hydrolysis. The plasma membrane proton pumps belong to the type III P-type
      ATPase subfamily, whereas Na+,K+-ATPase and Ca2+-ATPase are type II. Electron
      microscopy has revealed the overall shape of proton pumps, however, an atomic
      structure has been lacking. Here we present the first structure of a P-type
      proton pump determined by X-ray crystallography. Ten transmembrane helices and
      three cytoplasmic domains define the functional unit of ATP-coupled proton
      transport across the plasma membrane, and the structure is locked in a functional
      state not previously observed in P-type ATPases. The transmembrane domain reveals
      a large cavity, which is likely to be filled with water, located near the middle
      of the membrane plane where it is lined by conserved hydrophilic and charged
      residues. Proton transport against a high membrane potential is readily explained
      by this structural arrangement.

PMID- 18075597
TI  - Small RNAs: delivering the future.

PMID- 18075603
TI  - A Conversation With AAOS President James H. Beaty, MD.

PMID- 18075604
TI  - Computerized fluoroscopic-based navigation-assisted intramedullary nailing.
AB  - Intramedullary nailing, a fixation method commonly used for most diaphyseal
      fractures, relies heavily on fluoroscopy and delivers a significant amount of
      radiation to both patient and surgical team. Fluoroscopy-based computerized
      navigation enables accuracy in implant placement and minimizes soft-tissue
      dissection while reducing radiation. Navigation facilitates intramedullary
      nailing in determining entry-point location, insertion of locking and blocking
      screws, and nail and screw length measurement. We refer to our preliminary
      experience with 150+ cases to describe the technique of navigation-based
      intramedullary nailing and its various applications.

PMID- 18075605
TI  - Infantile idiopathic scoliosis.
AB  - This review of infantile idiopathic scoliosis highlights the clinical features,
      etiology, epidemiology, and treatment considerations that clearly distinguish
      this entity from the more common diagnosis of juvenile and adolescent idiopathic
      scoliosis. A comprehensive understanding of infantile idiopathic scoliosis
      provides the basis for reliable prediction of those curves that are likely to
      spontaneously resolve and those that will relentlessly progress if left
      untreated.

PMID- 18075606
TI  - Use of fluoroscopically guided intra-articular hip injection in differentiating
      the pain source in concomitant hip and lumbar spine arthritis.
AB  - We retrospectively tested the effectiveness of fluoroscopically guided intra-
      articular hip injection in differentiating the pain generator in patients with
      atypical lower extremity pain and concomitant radiographic hip and spine
      arthritis. After the hip injection, 74 of 83 patients had pain relief (pain score
      improvement, 7.2 to 2.7) and functional improvement (Harris hip score [HHS]
      improvement, 54.3 to 80.4). Of those 74 patients, 50 (mean preoperative HHS,
      60.3) went on to hip arthroplasty (for 48 of these 50, mean HHS increased to
      84.4); the other 24 patients are being treated nonoperatively so far. The 11
      patients who did not experience pain relief (9 after initial injection plus 2
      after total hip arthroplasty) were found to have spinal pathology and were
      treated accordingly. STATISTICS: sensitivity, 100%; specificity, 81%; positive
      predictive value, 97%; negative predictive value, 100%.

PMID- 18075607
TI  - Minimal-incision total shoulder arthroplasty: a cadaveric study.
AB  - Traditional exposure for total shoulder arthroplasty (TSA) is a deltopectoral
      incision of approximately 17 cm. Recent literature suggests that minimally
      invasive surgery for knee and hip arthroplasties may be successful in reducing
      perioperative morbidity and improving patient satisfaction. In the study reported
      here, we evaluated a minimal-incision approach to TSA. Using 10 fresh-frozen
      cadaveric shoulders, we performed TSAs through a 6-cm incision originating at the
      center of the coracoid process and extending distally along the deltopectoral
      interval. Soft-tissue releases, humeral osteotomy, and glenoid resurfacing were
      performed in all 10 cadaver shoulders using standard TSA retractors and guides.
      No skin or soft-tissue complications were observed. We conclude that it is
      technically possible to perform TSA through an appropriately placed minimal (6
      cm) incision.

PMID- 18075608
TI  - Impact of erythropoietin on allogenic blood exposure in orthopedic surgery.
AB  - Joint reconstruction surgery is associated with significant blood loss, and
      patients often require perioperative transfusions. Recombinant human
      erythropoietin (epoetin) can be used in anemic patients scheduled for elective,
      noncardiac, nonvascular surgery to reduce the need for transfusions. In the study
      reported here, patients with a preoperative hemoglobin level of 10 to 13 g/dL
      were treated with epoetin. Our analysis showed that transfusions were given to 3
      (8%) of the 38 patients who received epoetin before surgery and 20 (57%) of the
      35 historical controls (P<.001) and that length of hospital stay did not differ
      significantly between the 2 groups. Our results provide further support for use
      of epoetin as an effective strategy for reducing exposure to allogenic blood in
      orthopedic surgery.

PMID- 18075609
TI  - Acute calcific tendinitis of the hand: 2 case reports involving the abductor
      pollicis brevis.

PMID- 18075610
TI  - Bilateral luxatio erecta humeri and bilateral knee dislocations in the same
      patient.
AB  - Bilateral knee dislocations seldom occur, and fewer than a dozen cases of
      bilateral luxatio erecta humeri (erect dislocation of the shoulder) have been
      reported. Here we present the case of a patient who sustained bilateral knee
      dislocations and bilateral luxatio erecta humeri in a motorcycle accident.
      Transient neurologic compromise resolved with closed reduction of the bilateral
      shoulder and left knee dislocations. To our knowledge, this is the first case
      report of a patient with this combination of injuries.

PMID- 18075611
TI  - Tissue-engineered meniscal constructs.
AB  - The medial and lateral menisci play important roles in knee biomechanics,
      kinematics, and stability. Unfortunately, these structures are prone to damage
      and, because of a tenuous blood supply, have great difficulty healing. Many
      interventions have been proposed for treatment of damaged meniscal tissue, but
      most surgical options are fraught with difficulties, from continued
      osteoarthritic degeneration to potential for disease transmission. The field of
      tissue engineering has made wide inroads into constructing meniscal tissue.
      Investigations involving collagenous tissue, meniscal fibrochondrocytes,
      chondrocytes, synthetic scaffolds, and gene therapy have all been reported in the
      literature. Despite these advances, however, more work needs to be done,
      including incorporating concepts and applications from other engineering
      disciplines, to potentiate the possibility of a tissue-engineered meniscus that
      approximates native tissue. In particular, the histologic, morphologic, and
      biomechanical properties of tissue-engineered meniscal constructs must be better
      understood to facilitate this goal.

PMID- 18075612
TI  - Connecting multiple open wounds to a single negative-pressure dressing.
AB  - We present a new technique for connecting open wounds to a negative-pressure
      device. In this technique, a flexible, small-diameter intravenous tube is used to
      bridge the gap between open wounds on the same extremity. After these connections
      are made, the first layer of plastic is placed, and only 1 fenestrated connection
      is made to the device. This technique allows use of multiple sponges with only 1
      fenestrated cap and 1 connection to the device. The smaller intravenous tube must
      not be placed directly on skin, as it may cause a pressure ulcer underneath.

PMID- 18075613
TI  - Management of pelvic fractures during pregnancy.
AB  - Pelvic or acetabular fractures during pregnancy are rare, and information on
      managing such complex incidents has been limited. Over several years, we have
      gained significant experience in handling such cases. Of the 1345 pelvic and
      acetabular fractures treated at our level I trauma center between 1987 and 2002,
      15 (1.1%) occurred in pregnant women. Eleven women received conservative
      treatment, and 4 were treated surgically. Of the 16 fetuses, 12 survived, and 4
      pregnant women had nonviable pregnancies. One of the 15 pregnant women died. We
      describe our cases and propose treatment guidelines. The dilemma presented in a
      multitrauma situation at various stages of pregnancy necessitates making
      management modifications involving timing of surgery and delivery, use of
      radiation for imaging, and choice of appropriate surgical procedure.

PMID- 18075614
TI  - Orthopedic trauma in pregnancy.
AB  - Trauma sustained during pregnancy can trigger uncertainty and anxiety for patient
      and orthopedic surgeon alike. In particular, orthopedic-related injuries raise
      concerns about preoperative, intraoperative, and postoperative care. In this
      article, we review common concerns about radiation exposure, leukemia, pain
      management, anticoagulation, and anesthesia. One finding is that radiation risk
      is minimal when obtaining x-rays for operative planning, provided that the
      cumulative dose is within 5 rad. We also address safety concerns about patient
      positioning and staff radiation exposure. In addition, we found that most
      anesthetics used in pregnancy are category C (ie, safe). Perioperative opioid use
      for pain management is recommended with little risk. Regarding anticoagulation,
      low-molecular-weight heparin and fondaparinux are the safest choices. Last,
      pregnancy is not a contraindication to operative management of pelvic and
      acetabular fractures.

PMID- 18075615
TI  - Traumatic disruption of pubis symphysis with accompanying posterior pelvic injury
      after natural childbirth.

PMID- 18075616
TI  - GPs and the environment.

PMID- 18075617
TI  - Skin malignancies in general practice.
AB  - The BEACH program, a continuous national study of general practice activity in
      Australia, gives us an overview of consultations involving the management of
      malignant skin neoplasms across the geographic classes of Australia. This
      provides a backdrop against which articles in this issue of Australian Family
      Physician can be further considered.

PMID- 18075618
TI  - Climate change and primary health care.
AB  - BACKGROUND: Climate change and rising average global temperatures threaten to
      disrupt the physical, biological and ecological life support systems on which
      human health depends. OBJECTIVE: This article overviews the evidence for human
      induced climate change, the predicted health impacts, and the role of primary
      health care professionals in managing these impacts. DISCUSSION: Climate change
      has substantial potential health effects. These include heat stress related to
      heatwaves; injuries related to extreme weather events such as storms, fires and
      floods; infectious disease outbreaks due to changing patterns of mosquito borne
      and water borne diseases; poor nutrition from reduced food availability and
      affordability; the psychosocial impact of drought; and the displacement of
      communities. Primary health care has an important role in preparing for and
      responding to these climate change related threats to human health.

PMID- 18075619
TI  - Drought and its effect on mental health--how GPs can help.
AB  - BACKGROUND: Drought has been a major stressor affecting rural New South Wales
      communities since late 2001. While much is known about the effects on mental
      health of acute natural disasters, there is less research available on the effect
      to communities of chronic natural disasters. Of great concern for Australian
      rural communities is that independent of drought, the rate of suicide for some
      groups is higher in rural than urban communities, while access to mental health
      services is less. OBJECTIVE: This article explores how general practitioners can
      identify and respond to the drought related mental health needs of farming
      residents. DISCUSSION: Limited availability of mental health services to rural
      communities increases reliance on GPs for mental health care. Residents of
      farming communities report experiencing substantial distress in relation to the
      drought. The local GP is a key source of consultation, advice and treatment.
      Early intervention is a critical task in improving the mental health of rural
      communities. Early intervention provided by GPs will be enhanced through: working
      closely with other community agencies to promote early effective intervention for
      mental health problems, improve access to advice and initial consultation, and
      facilitate urgent consultation when needed; increasing access to services for
      farmers and responding promptly to needs; and utilising the support of rural
      organisational workers.

PMID- 18075620
TI  - Fighting with fire--how bushfire suppression can impact on fire fighters' health.
AB  - BACKGROUND: Each year bushfire threatens Australia's rural, forest, and urban
      rural areas. Australia's rural fire fighters work to curtail this threat in hot,
      smoky conditions, often at risk to their physical health. General practitioners,
      especially in rural areas, can help preserve the health of fire fighters during
      the fire season by understanding the stressors they face on the fireground.
      OBJECTIVE: This article outlines how the key fireground stressors of work
      intensity and duration, heat (from the weather, the fire, and the fire fighter's
      own exertion) and smoke impact on the health of fire fighters. Practical advice
      for GPs treating Australia's rural fire fighters is also included. DISCUSSION:
      General practitioners can help preserve fire fighters' health during bushfire
      suppression in a number of ways, including: identifying fire fighters at risk of
      cardiac distress during physical labour and educating them about the early
      warning signs; advocating regular exercise; discouraging smoking; and promoting
      the benefits of maintaining fluid, carbohydrate, and electrolyte levels during a
      shift.

PMID- 18075621
TI  - Recycled water and human health effects.
AB  - BACKGROUND: Recent drought conditions and diminishing drinking water storage
      levels in Australian capital cities have led to increasing attention being
      directed to water recycling and the use of alternative water sources for urban
      domestic use. Despite the 'in principle' acceptance by the Australian public for
      water recycling, support for proposed schemes is constrained by public perception
      of possible adverse health effects from exposure to micro-organisms and chemical
      contaminants. OBJECTIVE: This article describes current research investigating
      the health impacts of using recycled water for urban nondrinking purposes.
      DISCUSSION: Two complementary research approaches, quantitative microbial risk
      assessment and epidemiology, may be employed to assess health impacts of using
      recycled water for nondrinking or drinking purposes. The first of these
      approaches involves water quality monitoring and experimental studies. The second
      involves disease surveillance in which genera practitioners may play a part.

PMID- 18075622
TI  - Environmental toxins and health--the health impact of pesticides.
AB  - BACKGROUND: Pesticides, including insecticides, herbicides and fungicides, are
      widely used in Australian agriculture. There is growing public concern about
      their impact on human health. OBJECTIVE: This article reviews the available
      evidence about the potential chronic health effects of pesticides, particularly
      relating to children and breastfeeding women, and discusses the potential role of
      organic food in decreasing risk. DISCUSSION: Exposure to pesticides can occur
      directly from occupational, agricultural and household use, and indirectly
      through the diet. Studies suggest that pesticides may be related to various
      diseases, including cancers, as well as having neurological, mental and
      reproductive effects. Children may be more susceptible to the effects of
      pesticides due to increased exposure via food and breast milk, underdeveloped
      detoxification pathways, and longer life expectancy in which to develop diseases
      with long latency periods. Some studies suggest that organic food consumption may
      lead to reduced pesticide exposure, however, there is a lack of direct evidence
      that organic food is a healthier option. Recommendations to minimise pesticide
      exposure include avoiding the use of pesticides at home or in the garden,
      limiting skin exposure to pesticides through the use of appropriate protective
      gear, and consuming organic food.

PMID- 18075623
TI  - Healthy patients, healthy planet--green recommendations for GP health promotion.
AB  - BACKGROUND: Prevention of illness and early detection of disease are recognised
      as part of the challenge all communities face in their quest to achieve
      sustainability. OBJECTIVE: This article examines how the preventive health
      practices of general practitioners have benefits for the environment, and
      explores opportunities for GPs to encourage patients to maintain their health in
      ways that have a low environmental impact. DISCUSSION: Our environment is
      threatened by the impact of human activity. Ecosystem degradation is in turn, a
      threat to the health and wellbeing of humans. Preventive health practices are
      self evidently beneficial to the health of patients. General practitioners have
      opportunities to modify their health promotion advice so that patients can
      improve their own health in ways that also help the environment.

PMID- 18075624
TI  - 'Detox': science or sales pitch?
AB  - There is no question that the world is becoming increasingly toxic, with
      worldwide dissemination of industrial chemicals, pesticides, heavy metals and
      radioactive elements. Many of these toxins have demonstrated harmful effects
      including cancer, reproductive, metabolic, and mental health effects. It is also
      known that many toxins undergo bioaccumulation through the food chain and that
      synergistic effects can occur whereby combinations of toxins can be more potent
      than the sum of individual toxins.

PMID- 18075625
TI  - Lead--toxicology and assessment in general practice.
AB  - BACKGROUND: Despite a consistent fall in the number of reported cases of
      inorganic lead toxicity, lead remains an important toxicant. While much of the
      pathology caused by lead is known, much remains to be established regarding its
      mutagenicity and teratogenicity. OBJECTIVE: This article briefly outlines aspects
      of lead toxicity relevant to general practice, and provides an outline for taking
      a workplace exposure medical history. DISCUSSION: Recent trends show a continuous
      decline in the number of lead toxicity cases among workers and nonoccupational
      cases in adults and children. The protean manifestations of lead toxicity make it
      difficult for doctors to consider it as a differential diagnosis. A basic
      understanding of lead toxicology is helpful when assessing its clinical
      presentation, ordering laboratory tests, advising patients how to avoid workplace
      exposure, and in understanding why it remains a major concern as a mutagen and
      teratogen.

PMID- 18075626
TI  - Recurring melanoma--a case study.
AB  - BACKGROUND: Melanoma occurs more frequently in Australia then anywhere else in
      the world, and has a notoriously unpredictable prognosis and the potential for
      very late recurrence. OBJECTIVE: This article presents a case study of a patient
      who experienced a local melanoma recurrence 19 years after initial diagnosis and
      treatment, and again 8 years later. DISCUSSION: Definitive treatment, followed by
      a long disease free period and the cessation of specialist follow up, may lull
      one into believing a melanoma is 'cured'. As the main long term medical provider,
      the general practitioner is uniquely placed to detect late recurrence at a stage
      that could allow life saving treatment.

PMID- 18075627
TI  - Exercise based cardiac rehabilitation in chronic heart failure.
AB  - People with chronic heart failure often present to their general practitioner
      with questions about their participation in cardiac rehabilitation programs. This
      article outlines the risks and benefits of such programs.

PMID- 18075628
TI  - Age related macular degeneration--should your patients be taking additional
      supplements?
AB  - BACKGROUND: The use of over-the-counter complementary medicines and supplements
      is growing. Patients with age related macular degeneration (AMD) are likely to
      have heard of, or are possibly already taking, additional supplements that may
      increase their chances of retaining useful eyesight. OBJECTIVE: This article
      looks specifically at evidence regarding the effects of over-the-counter oral
      supplements such as antioxidants and omega-3 fatty acids on AMD. DISCUSSION: Diet
      manipulation and supplementation has a role to play in modifying the risk of
      disease progression in AMD patients. A combination of vitamins C and E, beta
      carotene, zinc oxide and cupric oxide has been shown to reduce the rate of visual
      loss in dry AMD. However, commercially available preparations do not always
      recommend the correct intake that would match levels found in clinical trials.
      Other carotenoids such as lutein and zeaxanthin may also be beneficial, intake of
      these can be increased by altering diet alone. Other useful dietary changes
      include reducing both animal and vegetable fats and increasing the consumption of
      fish and nuts.

PMID- 18075629
TI  - Primary hyperparathyroidism and familial hyperparathyroid syndromes.
AB  - BACKGROUND: Ninety percent of cases of hypercalcaemia are due to primary
      hyperparathyroidism or hypercalcaemia of malignancy. OBJECTIVE: This article
      outlines the diagnostic features of primary hyperparathyroidism and determines
      who would benefit from parathyroidectomy. It also aims to raise awareness of
      familial hyperparathyroid syndromes. DISCUSSION: Diagnosis of primary
      hyperparathyroidism requires hypercalcaemia, elevated or inappropriately normal
      serum parathyroid hormone and a fractional urinary excretion of calcium greater
      than 0.02. Many patients benefit from parathyroidectomy, which has a high rate of
      cure.

PMID- 18075630
TI  - Clinical use of anti-TNF-alpha biological agents--a guide for GPs.
AB  - BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) inhibitors are a new class
      of injectable drugs, under the umbrella term 'biological agents', now available
      for the treatment of rheumatoid arthritis and other chronic inflammatory
      conditions including juvenile idiopathic arthritis, Crohn disease, psoriasis and
      psoriatic arthritis. OBJECTIVE: The aim of this review is to provide an overview
      of TNF-alpha inhibitors and highlight the key practical issues of relevance to
      general practitioners. DISCUSSION: TNF-alpha inhibitors may have a potent effect
      in reducing inflammation and possibly inducing remission where conventional
      disease modifying drugs have failed to do so. These drugs are associated with an
      increased risk of infection as well as other potentially serious side effects.
      Their use is restricted to the relevant specialist prescribing the drug and are
      only available on the Pharmaceutical Benefits Scheme under strict prescribing
      criteria. The role of the GP is critical in identifying patients suitable for
      referral to consider commencing treatment and in monitoring patients on long term
      therapy.

PMID- 18075631
TI  - Fitting disability into practice--focus on spinal cord injury.
AB  - BACKGROUND: People with specialised needs such as spinal cord injury (SCI) may
      not feature prominently in the caseload of the general practitioner. However,
      when people with chronic disabilities are aggregated, they constitute a
      reasonable percentage of consultations. It may be difficult to deliver high
      quality health care for such complex patients. OBJECTIVE: We propose a method for
      integration of health care and prevention activities for patients with SCI in
      general practice, using tools such as a structured questionnaire, general
      practice management plans and team care arrangements. DISCUSSION: Practice
      structures can efficiently and effectively accommodate people with disabilities.
      Tools can serve as clinical prompts, help with planning, save time, and be
      financially rewarding. Importantly, they can anchor a 12 month cycle of
      preventive health care, allowing systematic monitoring and increasing
      intensity/coordination of professional input for those identified with greatest
      needs.

PMID- 18075632
TI  - Clinical teacher training--maximising the 'ad hoc' teaching encounter.
AB  - Classically, the patient is absent when the learner makes an 'ad hoc' corridor
      enquiry of their supervisor. This teaching encounter challenges the supervisor to
      ensure that the educational benefit is not limited by the brevity of the
      encounter. Focusing on some of the critical steps or teaching skills involved in
      the learning process increases the efficiency and effectiveness of this type of
      teaching encounter. Educationalists have provided models to optimise this
      fleeting corridor enquiry. This article presents a range of scripted clinical
      teaching scenarios that demonstrate the sound educational theory and principles
      underlying one such model--the 'one minute preceptor' or 'five step microskills
      model' of clinical teaching.

PMID- 18075633
TI  - Unsafe sharps management.
AB  - Case histories are based on actual medical negligence claims or medicolegal
      referrals. However, certain facts have been omitted or changed by the author to
      ensure the anonymity of the parties involved. This article examines an incident
      involving a patient who sustained a 'needlestick' injury at a general
      practitioner's surgery. Advice on how to manage a 'needlestick' injury and
      strategies to ensure the safe management of sharps are outlined.

PMID- 18075634
TI  - Living with toxic poisioning.
AB  - In 1991 I was working as an administration officer at a school in North
      Queensland. I worked with two other women in a very small office and there were
      three other offices nearby, each with one person in them. The education
      department decided to put down new flooring around these offices, down the
      adjoining stairway and along the adjoining hallway. The new flooring was made up
      of coloured chips spread over the floor coated by a two part resin. At the time
      the flooring was being laid, the weather was very wet and humid. The two part
      coating would not set. It was soft to touch and smelt toxic. After complaints
      from office staff to the education department, the floor was patched up. This
      process happened about three times over a 3 year period.

PMID- 18075635
TI  - Weapons of war--humanitarian and medical impact.
AB  - Most of us have patients who have loved ones living far away, sometimes in
      conflict zones or in other dangerous locations, and we share in the anxiety and
      distress that such situations bring to relatives.

PMID- 18075636
TI  - Inadequate chemoprophylaxis and the risk of malaria.
AB  - BACKGROUND: Malaria is an important disease for Australian travellers,
      particularly to Papua New Guinea. Travellers often seek health advice from their
      general practitioner before travel or if they develop illness after travel.
      METHOD: A retrospective cohort investigation into malaria risk in a group of
      adult Australians that trekked the Kokoda trail in Papua New Guinea. RESULTS: Six
      of 38 group members were diagnosed with malaria on return from Papua New Guinea.
      None of the 12 individuals who took chemoprophylaxis for the recommended period
      post-travel developed malaria compared to 4/24 travellers who terminated
      prophylaxis prematurely or 2/2 who took no chemoprophylaxis. DISCUSSION:
      Chemoprophylaxis is effective if taken for the full recommended period following
      travel to a malaria endemic area; 4 weeks for doxycycline and mefloquine, and 7
      days for atovaquone+proguanil. Malaria is a likely cause of illness in recently
      returned travellers from Papua New Guinea who develop a febrile illness.

PMID- 18075637
TI  - Physical activity promotion in general practice--patient attitudes.
AB  - BACKGROUND: Long term adherence to primary care physical activity intervention is
      poor. This study explored attitudes and subjective experiences of those who
      received such an intervention. METHODS: Nested qualitative study within mixed
      methods approach, involving 15 sedentary adults from urban and rural general
      practices in New Zealand. Semistructured telephone interviews were conducted,
      transcribed, and analysed using an inductive approach to identify themes.
      RESULTS: Four themes emerged including: tailoring of advice given; barriers to
      physical activity such as weather, physical environment, time, health and
      psychological limitations; internal motivators such as immediate or long term
      psychological, health or spiritual benefits, commitment, and guilt; and the role
      of significant others such as health and exercise professionals in initiating
      advice and continuing support, social interaction and commitment or contracts
      made to others. DISCUSSION: This study highlights the need for a personalised
      approach, continued structured external support and the need to focus on barriers
      and facilitators.

PMID- 18075638
TI  - GPs want tailored, user friendly evidence summaries--a cross sectional study in
      New South Wales.
AB  - BACKGROUND: This study aimed to measure the use of, and barriers to, using
      evidence among general practitioners since computerisation of general practice;
      GP preference for patient involvement in health care decisions; and GPs'
      preferred strategies to increase the use of evidence. METHODS: A cross sectional,
      open ended telephone survey was conducted with 107 (out of 155) New South Wales
      GPs randomly selected from the New South Wales Medical Board register. The survey
      sought self report to open ended questions about information sources informing
      decisions, perceived barriers to using evidence, and suggested strategies to
      improve clinical decisions, plus Degner scale for patient involvement. RESULTS:
      Evidence based sources remained the least likely to be used for informing
      decisions about patient care (23.4%). Opinion based sources were most commonly
      used (50.5%), with industry sponsored sources second (27.1%). Rural GPs were more
      likely to use opinion based sources (OR=1.55, 95% CI: 1.00-2.40). The most common
      perceived barriers were 'a lack of time' (22.0%), 'a lack of evidence or
      conflicting evidence' (13.1%), 'not knowing where to look' (10.3%) and 'not being
      able to tailor evidence to individual patients' (9.3%). The majority of GPs
      (72.0%) preferred patients to have some role in decision making. The most common
      suggestions for improving decision making were 'simply formatted evidence
      summaries' (28.0%) and 'mechanisms for tailoring evidence with individual
      patients' (13.1%). DISCUSSION: The use of evidence based sources for clinical
      decision making in general practice remains limited. Potential strategies to
      overcome this should focus on providing more user friendly evidence summaries,
      involving patients in evidence based decision making, and finding mechanisms to
      tailor evidence to individual patients.

PMID- 18075639
TI  - Registrar clinical teaching visits--evaluation of an assessment tool.
AB  - BACKGROUND: External clinical teaching (ECT) visits provide structured feedback
      to general practice registrars concerning their performance during training. This
      study sought to evaluate the acceptability to general practice registrars of a
      quantitative, criterion based, formative assessment tool to be administered
      during ECT visits. METHODS: We used a standardised, validated consultation
      feedback proforma and set the 1-5 rating at the FRACGP exam standard. An
      evaluation questionnaire was given to the registrar and returned separately.
      RESULTS: Twenty-six ECT visits were conducted from September 2005 to March 2006.
      A total of 21 registrar feedback forms were received (response rate 80.1%).
      Twenty (95%) registrars agreed the form provided useful feedback and was a useful
      prompt for discussion with their medical educator. Eighty-six percent felt their
      ratings were fair. DISCUSSION: Quantitative formative assessment was well
      received by the majority of general practice registrars. This tool complements
      other formative assessment tools used in general practitioner training.

PMID- 18075640
TI  - Management of skin cancer in Australia--a comparison of general practice and skin
      cancer clinics.
AB  - BACKGROUND: Skin cancer is common in Australia and its increasing incidence has
      been matched by an increase in specifically focused skin cancer clinics staffed
      by general practitioners. This study compares the management of skin cancer in
      general practice with that of skin cancer clinic networks. METHODS: Analysis of
      billing data relating to management of skin cancer from 1 July 2005 to 30 June
      2006 in three Queensland general practices (metropolitan, provincial, and rural)
      representing 23 100 patients and 23 doctors. As far as possible, methods were
      matched to those used in two published studies of skin cancer clinics. RESULTS:
      Of the 1417 skin cancers: 31 melanomas and 1361 nonmelanoma skin cancers (NMSC)
      were treated by excision, and 25 NMSC were treated nonsurgically. The biopsy to
      treatment ratio in general practice was 0.7 and the number needed to treat (NNT)
      was 39, compared with 3.1 and 29 in one skin cancer clinic network and 0.5 and 24
      in the other. Eighty-seven percent of skin cancer excisions were closed by
      primary repair and 54% of all excised lesions were malignant, compared with 42
      and 60% in one network and 76 and 46% in the other, respectively. DISCUSSION: The
      benign to malignant excision rate was similar in general practice and the skin
      cancer clinic networks, but one network reported very different rates of biopsy
      and complex wound closure. This raises questions as to whether outcomes are
      improved by these measures. These results demonstrate the usefulness of three
      billing data outcome measures in comparing activity in different clinical
      settings. However, the billing based NNT may not be a useful measure.

PMID- 18075642
TI  - Heterogeneous catalysis with nickel-on-graphite (Ni/Cg).
AB  - Impregnation of nickel(II) onto graphite, upon reduction in situ, leads to a
      reagent that catalyzes both C-H and C-C bond formations between aryl halides, or
      aryl pseudo-halides, and various organometallics. Cross-couplings, most notably
      with tosylates, can lead to either reduced aromatics, biaryls, or styrenes as
      products under the influence of Ni/Cg. The catalyst is inexpensive, non
      pyrophoric, and reusable.

PMID- 18075643
TI  - Chiral recognition in noncovalent bonding interactions between helicenes: right
      handed helix favors right-handed helix over left-handed helix.
AB  - Our studies of helicenes are summarized in regard to chiral recognition
      phenomenon in noncovalent bonding interactions. The interactions between helical
      molecules show a tendency for pairs of the same configuration of the helicenes to
      form more stable complexes than pairs of enantiomeric helicenes. The observations
      are made in charge transfer complexation, crystallization, homocoupling reaction,
      layer structure formation, self-aggregation, and double helix formation. The
      interactions between a helicene and a right-handed helical polymer, double strand
      DNA, are also described.

PMID- 18075644
TI  - Molecular rearrangements through thermal [1,3] carbon shifts.
AB  - Molecular rearrangements through thermal [1,3] carbon shifts, such as
      vinylcyclopropane-to-cyclopentene and vinylcyclobutane-to-cyclohexene
      isomerizations, were recognized and exemplified repeatedly from 1960-1964.
      Serious mechanistic studies of these and related rearrangements over the past 40
      years have provided ample grounds for interpreting them as processes taking place
      by way of conformationally flexible but not statistically equilibrated diradical
      intermediates. Orbital symmetry theory fails to account for the stereochemical
      characteristics of [1,3] carbon shifts. For sigmatropic reactions of this class
      the theory can no longer be retained as a valid basis for mechanistic
      interpretations, or even as a serious contender for consideration as a
      mechanistic possibility.

PMID- 18075645
TI  - Phenothiazine as a redox-active DNA base substitute: comparison with
      phenothiazine-modified uridine.
AB  - Phenothiazine can be incorporated as a redox-active probe into DNA in two
      conceptually different ways: the non-nucleosidic DNA base surrogate exhibits
      similar properties to 10-methylphenothiazine but with no preferential base
      pairing properties, whereas the phenothiazine-modified uridine has different
      optical and electrochemical properties, but exhibits preferred Watson-Crick base
      pairing with adenine.

PMID- 18075646
TI  - Remarkable incorporation of the first sulfur containing indole derivative:
      another piece in the biosynthetic puzzle of crucifer phytoalexins.
AB  - The first sulfur labelled compound, [(2)H(4),(34)S]indolyl-3-acetothiohydroxamic
      acid, is incorporated into the phytoalexins cyclobrassinin and spirobrassinin and
      the indole glucosinolate glucobrassicin, indicating that both biosynthetic
      pathways are closely related.

PMID- 18075647
TI  - Cobalt-catalyzed reductive Mannich reactions of 4-acryloylmorpholine with N-tosyl
      aldimines.
AB  - Using cobalt catalysis, diethylzinc promotes the conjugate reduction of 4
      acryloylmorpholine to produce the corresponding ethylzinc enolate, which reacts
      with N-tosyl aldimines to afford beta-aminoamides.

PMID- 18075648
TI  - Synthesis and inhibitory effect on fat accumulation of (-)-ternatin derivatives
      modified in the beta-OH-D-Leu(7) moiety.
AB  - An efficient synthesis of (-)-ternatin derivatives directed toward their SAR at
      the beta-OH-D-Leu(7) moiety and their biological activities against 3T3-L1 murine
      adipocytes are described.

PMID- 18075649
TI  - Development of polysilane-supported palladium/alumina hybrid catalysts and their
      application to hydrogenation.
AB  - Novel immobilized Pd catalysts, polysilane-supported palladium/alumina hybrid
      catalysts, have been developed. The catalysts showed high catalytic activity for
      hydrogenation, and could be used in an organic solvent or under solvent-free
      conditions.

PMID- 18075650
TI  - Dyotropic rearrangement of alpha-lactone to beta-lactone: a computational study
      of small-ring halolactonisation.
AB  - Transition structures have been optimised using the B3LYP/6-31+G* density
      functional level method, in vacuum and in implicit (PCM) and explicit (DFT/MM)
      aqueous solvation, for the degenerate rearrangement of the alpha-lactone derived
      by the formal addition of Cl(+) to acrylate anion and for the dyotropic
      rearrangement of this to the beta-lactone. Despite being lower in energy than the
      alpha-lactone, there is no direct pathway to the beta-lactone from the acrylate
      chloronium zwitterion, which is the transition structure for the degenerate
      rearrangement. This may be rationalised by consideration of the unfavorable angle
      of attack by the carboxylate nucleophile on the beta-position; attack on the
      alpha-position involves a less unfavorable angle. Formation of the beta-lactone
      may occur by means of a dyotropic rearrangement of the alpha-lactone. This
      involves a high energy barrier for the acrylate derived alpha-lactone, but
      dyotropic rearrangement of the beta,beta-dimethyl substituted alpha-lactone to
      the corresponding beta-lactone involves a much lower barrier, estimated at about
      46 kJ mol(-1) in water, and is predicted to be a facile process.

PMID- 18075651
TI  - Metallo-nucleosides: synthesis and biological evaluation of hexacarbonyl dicobalt
      5-alkynyl-2'-deoxyuridines.
AB  - Reactions of 5-alkynyl-2'-deoxyuridines with dicobalt octacarbonyl Co2(CO)8 in
      THF at room temperature gave hexacarbonyl dicobalt nucleoside complexes (77-93%).
      The metallo-nucleosides were characterized, including an X-ray structure of a 1
      cyclohexanol derivative. In crystalline form, the Co-Co bond is perpendicular to
      the plane of the uracil base, which is found in the anti position. The level of
      growth inhibition of MCF-7 and MDA-MB-231 human breast cancer cell lines was
      examined and compared to results obtained with the alkynyl nucleoside precursors.
      The cobalt compounds displayed good antiproliferative activities with IC50 values
      in the range of 5-50 microM. Interestingly, the coordination of the dicobalt
      carbonyl moiety to 5-alkynyl-2'-deoxyuridines led to a significant increase in
      the cytotoxic potency for alkyl/aryl substituents at the non-nucleoside side of
      the alkyne, but in the case of hydrogen (terminal alkyne) or a silyl group, a
      decrease of the cytotoxic effect was observed. As demonstrated using examples for
      an active and a low active target compound, the cytotoxicity was significantly
      influenced by the uptake into the tumor cells and the biodistribution into the
      nuclei.

PMID- 18075652
TI  - Synthetic nucleic acid secondary structures containing the four stereoisomers of
      1,4-bis(thymine-1-yl)butane-2,3-diol.
AB  - The four stereoisomers of the double-headed acyclic nucleoside 1,4-bis(thymine-1
      yl)butane-2,3-diol were incorporated in the central position of four 13-mer
      oligonucleotides. The phosphoramidite building blocks were synthesized in four or
      six steps from either D- or L-2,3-O-isopropylidenethreitol. Two epimeric and
      fully deprotected double-headed nucleosides were analyzed by X-ray
      crystallography. The incorporation into oligonucleotides was hampered by steric
      hindrance and formation of a cyclic phosphate. The use of pyridinium chloride as
      the activator and a kinetic analysis based on 31P NMR of the coupling and
      detritylation processes led to improved yields of the oligonucleotides. In
      comparison with the (S)-GNA monomer, one of the four stereoisomers was found to
      show a similar destabilization of a DNA duplex, indicating that the additional
      base can be introduced without a thermal penalty. Another stereoisomer was found
      to induce a thermal stabilization of a DNA:RNA three-way junction. Thus, the
      stereochemistry of this acyclic double-headed nucleoside motif is important,
      indicating potential for the design of artificial nucleic acid secondary
      structures.

PMID- 18075653
TI  - RNA-selective cross-pairing of backbone-extended pyrrolidine-amide
      oligonucleotide mimics (bePOMs).
AB  - Pyrrolidine-amide oligonucleotide mimics (POMs) can cross-pair strongly with
      complementary parallel and antiparallel DNA and RNA targets in a sequence
      specific fashion. As a result POMs have significant potential for applications
      including in vivo gene silencing, diagnostics and bioanalysis. To further
      modulate the DNA- and RNA-recognition properties and fine-tune the physiochemical
      properties of POMs for nucleic acid targeting, backbone-extended pyrrolidine
      amide oligonucleotide mimics (bePOM I and II) were introduced. The bePOMs differ
      from the original POMs through the insertion of an additional methylene group
      into the backbone units, which increases the flexibility of the oligomers. bePOM
      I and II oligomers were synthesised using solid-phase peptide chemistry.
      Interestingly, UV thermal denaturation and circular dichroism studies reveals
      bePOM I and II can hybridise with complementary RNA, but not DNA.

PMID- 18075654
TI  - Intramolecular direct arylation in an A,C-functionalized calix[4]arene.
AB  - A recently developed efficient method for intramolecular direct arylation is
      employed on a doubly functionalized calix[4]arene fixed in the cone conformation.
      The reaction takes place in high yield leading to meta substituted
      calix[4]arenes. The functionalities are located at two opposite aromatic rings
      and the two possible diastereomers are obtained in a 1:1 ratio. Full sets of data
      including crystal structures for both isomers are presented. The NMR data reveal
      that even at temperatures up to 120 degrees C both isomers are fixed in a
      flattened cone conformation with the substituted aromatic units pointing
      outwards.

PMID- 18075655
TI  - Synthesis of fluorescein-labelled O-mannosylated peptides as components for
      synthetic vaccines: comparison of two synthetic strategies.
AB  - Mannose-binding proteins on the surface of antigen-presenting cells (APCs) are
      capable of recognizing and internalizing foreign agents in the early stages of
      immune response. These receptors offer a potential target for synthetic vaccines,
      especially vaccines designed to stimulate T cells. We set out to synthesize a
      series of fluorescein-labelled O-mannosylated peptides using manual solid phase
      peptide synthesis (SPPS) on pre-loaded Wang resin, in order to test their ability
      to bind mannose receptors on human APCs in vitro. A flexible and reliable method
      for the synthesis of fluorescein-labelled O-mannosylated glycopeptides was
      desired in order to study their lectin-binding properties using flow cell
      cytometry. Two synthetic strategies were investigated: incorporation of a
      fluorescein label into the peptide chain via a lysine side chain epsilon-amino
      group at the final stage of standard Fmoc solid phase peptide synthesis or
      attachment of the fluorescein label to the N(alpha)-amino group of a lysine with
      further incorporation of a mannosylated peptide unit through the side chain
      N(epsilon)-amino group. The latter strategy proved more effective in that it
      facilitated SPPS by positioning the growing mannosylated peptide chain further
      removed from the fluorescein label.

PMID- 18075656
TI  - Kinetic studies on the formation of DNA triplexes containing the nucleoside
      analogue 2'-O-(2-aminoethyl)-5-(3-amino-1-propynyl)uridine.
AB  - We have examined the kinetics of triple helix formation of oligonucleotides that
      contain the nucleotide analogue 2'-O-(2-aminoethyl)-5-(3-amino-1-propynyl)uridine
      (bis-amino-U, BAU), which forms very stable base triplets with AT. Triplex
      stability is determined by both the number and location of the modifications. BAU
      containing oligonucleotides generate triplexes with extremely slow kinetics, as
      evidenced by 14 degrees C hysteresis between annealing and melting profiles even
      when heated at a rate as slow as 0.2 degrees C min(-1). The association kinetics
      were measured by analysis of the hysteresis profiles, temperature-jump relaxation
      and DNase I footprinting. We find that the slow kinetics are largely due to the
      decreased rate of dissociation; BAU modification has little effect on the
      association reaction. The sequence selectivity is also due to the slower
      dissociation of BAU from AT than other base pairs.

PMID- 18075657
TI  - Efficient C2 functionalisation of 2H-2-imidazolines.
AB  - Alkylation and oxidation of 2H-2-imidazolines, followed by regioselective
      deprotection, thionation and microwave-assisted Liebeskind-Srogl reaction,
      efficiently led to 2-aryl-2-imidazolines as new analogues of p53-hdm2 interaction
      inhibitors (Nutlins).

PMID- 18075659
TI  - An improved synthesis of cis-4-phenyl-2-propionamidotetralin (4-P-PDOT): a
      selective MT(2) melatonin receptor antagonist.
AB  - A novel, efficient and diastereoselective procedure was developed for the gram
      scale synthesis of cis-4-phenyl-2-propionamidotetralin (4-P-PDOT), a selective
      MT(2) melatonin receptor antagonist. The synthetic strategy involved the
      conversion of 4-phenyl-2-tetralone to enamide followed by diastereoselective
      reduction affording cis-4-P-PDOT in good yield. The mechanism of the reduction
      step was explored by employing deuterated reagents.

PMID- 18075658
TI  - Synthesis of functionalised aromatic oligamide rods.
AB  - A current goal in synthetic chemistry is the design and synthesis of molecules
      that adopt well defined conformations-so called foldamers. In this manuscript we
      describe a modular approach for construction of rod shaped para-oligobenzamide
      molecules. Our approach permits regiospecific incorporation of side chains
      through a phenolic ether linkage on the scaffold; a feature that partly restricts
      the conformation of the rod through intramolecular hydrogen-bonding.

PMID- 18075660
TI  - Efficient generation of dendritic arrays of cross-linked hemoglobin: symmetry and
      redundancy.
AB  - Chemically connected protein arrays have significant diverse applications
      including the production of red cell substitutes, bioconjugate drug delivery, and
      protein therapies. In order to make materials of defined structure, there is a
      need for efficient and accessible reagents. While chemical cross-linking with a
      multi-subunit protein can be achieved in high yield, connecting proteins to one
      another in a dendritic assembly along with concurrent cross-linking has met with
      limited success. This has now been overcome through the design and implementation
      of a readily prepared reagent with added reaction sites that compensate for
      competing hydrolysis. N,N',N''-Tris[bis(sodium methyl phosphate)isophthalyl]
      1,3,5-benzenetricarboxamide (1), a hexakis(methyl phosphate) isophthalyl
      trimesoyl tris-amide, was designed and synthesized in high yield in three stages
      from a reactive trimesoyl core. This material has three pairs of coplanar cross
      linking reaction sites in a symmetrical array. The presence of three sets of
      sites greatly increases the probability that at least two sets will produce cross
      links within hemoglobin tetramers (in competition with hydrolysis) and thereby
      connect two cross-linked tetramers at the same time. Reaction of 1 with
      deoxyhemoglobin at pH 8.5 gives a material that contains two cross-linked
      hemoglobin tetramers connected to one another and to a constituent alphabeta
      dimer. Products were characterized by SDS-PAGE, MS, enzyme digestion and HPLC.
      The isolated dendritic-hemoglobin with 2.5 tetrameric components has the same
      oxygen affinity as native hemoglobin (P50 = 5.0 torr) and retains cooperativity
      (n50 = 2.0). Analysis of circular dichroism spectra indicates that the assembly
      retains proper folding of the globin chains while the hemes are in an altered
      environment.

PMID- 18075661
TI  - Synthesis of gem-difluorinated nucleoside analogues of the liposidomycins and
      evaluation as MraY inhibitors.
AB  - Two gem-difluoromethylenated nucleoside moieties of liposidomycins, 3 and 4, were
      designed and synthesized. Compound 3 was assembled from lactol 5 and gem
      difluoromethylenated nucleoside 6. In the synthesis of target molecule 4, the
      coupling of the trichloroacetimidate derivative of gem-difluoromethylenated
      furanose 7 with nucleoside 8 in the presence of TMSOTf gave the unexpected
      compound 16 when CH3CN was used as solvent. This results from acetonitrile acting
      as a nucleophile and participating in the glycosylation reaction. This unusual
      process may be correlated with the presence of the electron-withdrawing gem
      difluoro substituents at the C-2 position of furanose. Compound 3 demonstrated
      29% inhibition of MraY at 11.4 mM.

PMID- 18075662
TI  - A cholic acid-based fluorescent chemosenor for the detection of ATP.
AB  - A novel ditopic cholic acid-based fluorescent chemosensor for ATP, 1a, was
      designed and synthesized. Its interactions with phosphates, AMP, ADP, ATP, CTP,
      GTP, and TTP have been investigated. When ATP was added to a 1:1 aqueous CH3CN
      solution of the sensor at pH 7.4, a significant decrease in fluorescence of 1a
      was observed, whereas other guest molecules showed a much smaller effect. The
      complex between 1a and ATP was confirmed through combined UV, 1H, 13C and 31P NMR
      spectroscopic methods. The uniqueness of the new sensor is that it binds with ATP
      33-124 times more selectively than other nucleotides, as evidenced from the
      respective binding constants. 1a is a highly sensitive sensing probe; as little
      as 30 nM ATP can cause 15% fluorescence quenching of the sensor.

PMID- 18075663
TI  - Aryl triflates: useful coupling partners for the direct arylation of heteroaryl
      derivatives via Pd-catalyzed C-H activation-functionalization.
AB  - Aryl triflates were found to be suitable partners for the palladium catalyzed
      direct arylation of heteroaromatics via C-H activation-functionalization. The
      reaction conditions and the catalyst have a determining influence on the yields.
      The system combining PPh3 and Pd(OAc)2 using KOAc as base and DMF as solvent
      promotes the selective 2- or 5-arylations in moderate to high yields. Several
      heteroaromatics such as furan, thiophene, thiazole or oxazole derivatives have
      been employed successfully. The electronic properties of the aryl triflates also
      have a decisive influence on the yields of the coupling products. Electron-rich
      aryl triflates gave satisfactory results, whereas the electron-poor ones led to
      the formation of phenols.

PMID- 18075664
TI  - Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones.
AB  - Cycloaddition of pyridine N-imine with 6-alkyl-4-oxohex-5-ynoates followed by
      condensation with hydrazine provides concise access to pharmacologically active 6
      (pyrazolo[1,5-a]pyridin-3-yl)pyridazinones. For the first time alkynyl
      heterocycles are also shown to be effective dipolarophiles for pyridine N-imine,
      and analogous compounds can be accessed directly in modest yields through the
      reaction of 6-(alkyn-1-yl)pyridazin-3-one derivatives.

PMID- 18075665
TI  - A compact water-soluble porphyrin bearing an iodoacetamido bioconjugatable site.
AB  - A broad range of applications requires access to porphyrins that are compact,
      water-soluble, and bioconjugatable. A symmetrically branched hydrocarbon chain
      ('swallowtail') bearing polar end groups imparts high (>10 mM) aqueous solubility
      upon incorporation at one of the meso positions of a trans-AB-porphyrin. Two such
      swallowtail-porphyrins (1a, 1b) equipped with a conjugatable group (carboxylic
      acid, bromophenyl) have been prepared previously. The synthesis of three new
      water-soluble trans-AB-porphyrins is reported, where each porphyrin bears a
      diphosphonate-terminated swallowtail group and an amino (2a), acetamido (2b), or
      iodoacetamido (2c) group. The amine affords considerable versatility for
      functionalization. The iodoacetamide provides a sulfhydryl-reactive site for
      bioconjugation. Porphyrins were fully characterized in aqueous solution by 1H NMR
      spectroscopy (in D2O), ESI-MS, static absorption spectroscopy, and static and
      time-resolved fluorescence spectroscopy. Porphyrins 2a-2c exhibit characteristic
      porphyrin absorption and emission bands in aqueous solution, with a strong, sharp
      absorption band in the blue region (approximately 401 nm) and emission in the red
      region (approximately 624, 686 nm). Porphyrin 2b in aqueous phosphate buffer or
      phosphate-buffered saline solution exhibits a fluorescence quantum yield of
      approximately 0.04 and an excited singlet-state lifetime of approximately 11 ns.
      Collectively, the facile synthesis, amenability to bioconjugation, large spacing
      between the main absorption and fluorescence features, and long singlet excited
      state lifetime make this molecular design quite attractive for a range of
      biomedical applications.

PMID- 18075666
TI  - Reaction of 1-tert-butyl-3,4-diphenyl-1,2,4-triazol-5-ylidenes with a malonic
      ester.
AB  - Four stable carbenes, 1-tert-butyl-3,4-diaryl-1,2,4-triazol-5-ylidenes 1a-d,
      including new fluorine-containing compounds 1c,d, react with a malonic ester to
      afford heterocyclic zwitterionic compounds 5a-d. The reactions with more acidic
      compounds (ethyl acetoacetate, malononitrile and 1,3-dimethylbarbituric acid)
      proceed with substrate deprotonation to form the respective azolium salts 6a-c.
      The X-ray crystal structure of 5a was also determined.

PMID- 18075670
TI  - Systematic screens for human disease genes, from yeast to human and back.
AB  - Systematic screens for human disease genes have emerged in recent years, due to
      the wealth of information provided by genome sequences and large scale datasets.
      Here we review how integration of genomic data in yeast and human is helping to
      elucidate the genetic basis of mitochondrial diseases. The identification of
      nearly all yeast mitochondrial proteins and many of their functional interactions
      provides insight into the role of mitochondria in cellular processes. This
      information enables prioritization of the candidate genes underlying
      mitochondrial disorders. In an iterative fashion, the link between predicted
      human candidate genes and their disease phenotypes can be experimentally tested
      back in yeast.

PMID- 18075671
TI  - Processing of DNA damage clusters in human cells: current status of knowledge.
AB  - Eukaryotic cells exposed to DNA damaging agents activate important defensive
      pathways by inducing multiple proteins involved in DNA repair, cell cycle
      checkpoint control and potentially apoptosis. After the acceptance of the
      hypothesis that oxidatively generated clustered DNA lesions (OCDL: closely spaced
      DNA lesions) can be induced even by low doses of ionizing radiation or even
      endogenously, and significant advances have been made in the understanding of the
      biochemistry underlying the repair of closely spaced DNA lesions, many questions
      still remain unanswered. The major questions that have to be answered in the near
      future are: 1) how human cells process these types of DNA damage if they repair
      them at all, 2) under what conditions a double strand break (DSB) may be created
      during the processing of two closely spaced DNA lesions and 3) what type of
      repair protein interactions govern the processing of complex DNA damage? The data
      existing so far on human cells and tissues are very limited and in some cases
      contradicting. All of them though agree however on the major importance of
      gaining mechanistic insights on the pathways used by the cell to confront and
      process complex DNA damage located in a small DNA volume and the need of more in
      depth analytical studies. We selectively review recently-obtained data on the
      processing of non-DSB DNA damage clusters in human cells and tissues and discuss
      the current status of knowledge in the field.

PMID- 18075672
TI  - Alterations of some membrane transport proteins in Alzheimer's disease: role of
      amyloid beta-peptide.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease
      characterized clinically by progressive memory loss and decline in cognitive
      abilities and characterized pathologically by the presence of two types of
      abnormal deposits, i.e., senile plaques (SP) and neurofibrillary tangles (NFT),
      and by extensive synapse and neuronal loss. SP are composed of fibrillar amyloid
      beta-peptide (Abeta) surrounded by dystrophic neurites. Recent studies suggest
      two prospective mechanisms for Abeta-associated membrane dysfunction and
      subsequent neurotoxicity. One suggests that Abeta oligomers can form
      heterogeneous ion-channels in the cell membrane leading to cellular degeneration,
      while the second suggests insertion of Abeta oligomers in membrane lipid bilayers
      could induce the dysfunction of ion-channels or pumps by binding to or inducing
      oxidative modification of membrane proteins. In this review, we discuss the
      effects of Abeta on membrane proteins that are involved in cholinergic and
      glutamatergic pathways, and some ion-channels.

PMID- 18075673
TI  - Potential roles of abundant extracellular chaperones in the control of amyloid
      formation and toxicity.
AB  - The in vivo formation of fibrillar proteinaceous deposits called amyloid is
      associated with more than 40 serious human diseases, collectively referred to as
      protein deposition diseases. In many cases the amyloid deposits are extracellular
      and are found associated with newly identified abundant extracellular chaperones
      (ECs). Evidence is presented suggesting an important regulatory role for ECs in
      amyloid formation and disposal in the body. A model is presented which proposes
      that, under normal conditions, ECs stabilize extracellular misfolded proteins by
      binding to them, and then guide them to specific cell receptors for uptake and
      subsequent degradation. Thus ECs and their receptors may be critical parts of a
      quality control system to protect the body against dangerously hydrophobic
      proteins/peptides. However, it also appears possible that in the presence of a
      high molar excess of misfolded protein, such as might occur during disease, the
      limited amounts of ECs available may actually exacerbate pathology. Further
      advances in understanding of the mechanisms that control extracellular protein
      folding are likely to identify new strategies for effective disease therapies.

PMID- 18075674
TI  - Rapid C-carboxylation of nitro[(11)C]methane for the synthesis of ethyl nitro[2
      (11)C]acetate.
AB  - The labelling synthesis of ethyl nitro[2-(11)C]acetate, a synthetic intermediate
      feasible for (11)C-labelled PET tracers, by C-carboxylation of [(11)C]MeNO(2)
      with 1-ethoxycarbonylbenzotriazole, and its simple application are presented.

PMID- 18075675
TI  - Transcription factor logic using chemical complementation.
AB  - Chemical complementation was used to make a transcription factor circuit capable
      of performing complex Boolean logic.

PMID- 18075676
TI  - A general system for evaluating the efficiency of chromophore-assisted light
      inactivation (CALI) of proteins reveals Ru(II) tris-bipyridyl as an unusually
      efficient "warhead".
AB  - Chromophore-assisted light inactivation (CALI) of proteins is a potentially
      powerful tool in biological research for the triggered disruption of protein
      function. It involves the creation of chimeric molecules that can bind
      specifically to the protein target and can also sensitize the photo-generation of
      singlet oxygen, which inactivates the target protein. There remains a need for
      more efficient chromophores for singlet oxygen generation. Here we report a
      general and convenient system with which to evaluate the efficiency of
      chromophores in CALI both in crude extracts and in living cells. We employ this
      system to show that a readily available derivative of ruthenium(II) tris
      bipyridyl dication is an unusually efficient "warhead" for CALI, exhibiting a
      performance markedly superior to the commonly used organic fluorophore,
      fluorescein.

PMID- 18075677
TI  - Multiple calcium binding sites make calmodulin multifunctional.
AB  - Protein-protein or protein-ion interactions with multisite proteins are essential
      to the regulation of intracellular and extracellular events. There is, however,
      limited understanding of how ligand-multisite protein interactions selectively
      regulate the activities of multiple protein targets. In this paper, we focus on
      the important calcium (Ca(2+)) binding protein calmodulin (CaM), which has four
      Ca(2+) ion binding sites and regulates the activity of over 30 other proteins.
      Recent progress in structural studies has led to significant improvements in the
      understanding of Ca(2+)-CaM-dependent regulation mechanisms. However, no
      quantitative model is currently available that can fully explain how the
      structural diversity of protein interaction surfaces leads to selective
      activation of protein targets. In this paper, we analyze the multisite protein
      ligand binding mechanism using mathematical modelling and experimental data for
      Ca(2+)-CaM-dependent protein targets. Our study suggests a potential mechanism
      for selective and differential activation of Ca(2+)-CaM targets by the same CaM
      molecules, which are involved in a variety of intracellular functions. The close
      agreement between model predictions and experimental dose-response curves for CaM
      targets available in the literature suggests that such activation is due to the
      selective activity of CaM conformations in complexes with variable numbers of
      Ca(2+) ions. Although the paper focuses on the Ca(2+)-CaM pair as a particularly
      data rich example, the proposed model predictions are quite general and can
      easily be extended to other multisite proteins. The results of the study may
      therefore be proposed as a general explanation for multifunctional target
      regulation by multisite proteins.

PMID- 18075678
TI  - Proximate parameter tuning for biochemical networks with uncertain kinetic
      parameters.
AB  - It is commonly the case in biochemical modelling that we have knowledge of the
      qualitative 'structure' of a model and some measurements of the time series of
      the variables of interest (concentrations and fluxes), but little or no knowledge
      of the model's parameters. This is, then, a system identification problem, that
      is commonly addressed by running a model with estimated parameters and assessing
      how far the model's behaviour is from the 'target' behaviour of the variables,
      and adjusting parameters iteratively until a good fit is achieved. The issue is
      that most of these problems are grossly underdetermined, such that many
      combinations of parameters can be used to fit a given set of variables. We
      introduce the constraint that the estimated parameters should be within given
      bounds and as close as possible to stated nominal values. This deterministic
      'proximate parameter tuning' algorithm turns out to be exceptionally effective,
      and we illustrate its utility for models of p38 signalling, of yeast glycolysis
      and for a benchmark dataset describing the thermal isomerisation of alpha-pinene.

PMID- 18075680
TI  - "Imaging" combustion chemistry via multiplexed synchrotron-photoionization mass
      spectrometry.
AB  - The combination of multiplexed mass spectrometry with photoionization by tunable
      synchrotron radiation has proved to be a powerful tool to investigate elementary
      reaction kinetics and the chemistry of low-pressure flames. In both of these
      applications, multiple-mass detection and the ease of tunability of synchrotron
      radiation make it possible to acquire full sets of data as a function of mass,
      photon energy, and of the physical dimension of the system, e.g. distance from
      the burner or time after reaction initiation. The data are in essence an indirect
      image of the chemistry. The data can be quantitatively correlated and integrated
      along any of several dimensions to compare to traditional measurements such as
      time or distance profiles of individual chemical species, but it can also be
      directly interpreted in image form. This perspective offers an overview of flame
      chemistry and chemical kinetics measurements that combine tunable photoionization
      with multiple-mass detection, emphasizing the overall insight that can be gained
      from multidimensional data on these systems. The low-pressure flame apparatus is
      capable of providing isomer-resolved mass spectra of stable and radical species
      as a function of position in the flame. The overall chemical structure of the
      flames can be readily seen from images of the evolving mass spectrum as distance
      from the burner increases, with isomer-specific information given in images of
      the photoionization efficiency. Several flames are compared in this manner, with
      a focus on identification of global differences in fuel-decomposition and soot
      formation pathways. Differences in the chemistry of flames of isomeric fuels can
      be discerned. The application of multiplexed synchrotron photoionization to
      elementary reaction kinetics permits identification of time-resolved isomeric
      composition in reacting systems. The power of this technique is illustrated by
      the separation of direct and dissociative ionization signals in the reaction of
      C(2)H(5) with O(2); by the resolution of isomeric products in reactions of the
      ethynyl (C(2)H) radical; and by preliminary observation of branching to methyl +
      propargyl products in the self-reaction of vinyl radicals. Finally, prospects for
      future research using multiplexed photoionization mass spectrometry are explored.

PMID- 18075681
TI  - Dynamic imaging of molecules using high order harmonic generation.
AB  - We review recent progress towards imaging the electronic wavefunctions and
      nuclear dynamics of small molecules using the high order harmonics emitted when a
      molecule experiences an intense laser field. We illustrate that the essence of
      high harmonic emission is contained in the recombination amplitude between the
      continuum portion of the electronic wavefunction, that is formed through field
      ionization and which is accelerated and driven back to recollide in the laser
      field, and the bound electronic state. We review for the non-specialist some
      recent experimental and theoretical work dealing with high harmonic generation
      (HHG) in molecules. Particular attention is paid to two types of experiment
      recently performed in our group. The first of these types of experiment is the
      measurement of signatures of molecular electronic structure using HHG from
      molecules with a fixed orientation in space. The second is the use of HHG to
      track extremely fast proton rearrangement following ionization in light
      molecules, using the intrinsic temporal variation of the recolliding electron
      energy to extract these dynamics from measurements of the high harmonics.

PMID- 18075682
TI  - Physical electrochemistry of nanostructured devices.
AB  - This Perspective reviews recent developments in experimental techniques and
      conceptual methods applied to the electrochemical properties of metal-oxide
      semiconductor nanostructures and organic conductors, such as those used in dye
      sensitized solar cells, high-energy batteries, sensors, and electrochromic
      devices. The aim is to provide a broad view of the interpretation of
      electrochemical and optoelectrical measurements for semiconductor nanostructures
      (sintered colloidal particles, nanorods, arrays of quantum dots, etc.) deposited
      or grown on a conducting substrate. The Fermi level displacement by
      potentiostatic control causes a broad change of physical properties such as the
      hopping conductivity, that can be investigated over a very large variation of
      electron density. In contrast to traditional electrochemistry, we emphasize that
      in nanostructured devices we must deal with systems that depart heavily from the
      ideal, Maxwell-Boltzmann statistics, due to broad distributions of states (energy
      disorder) and interactions of charge carriers, therefore the electrochemical
      analysis must be aided by thermodynamics and statistical mechanics. We discuss in
      detail the most characteristic densities of states, the chemical capacitance, and
      the transport properties, specially the chemical diffusion coefficient, mobility,
      and generalized Einstein relation.

PMID- 18075683
TI  - Evidence of a water layer in solid-contact polymeric ion sensors.
AB  - This paper presents the very first direct structural evidence for the formation
      of a 100 +/- 10 A water layer in coated-wire polymeric-membrane ion-selective
      electrodes (ISEs).

PMID- 18075684
TI  - The structure of protonated acetone and its dimer: infrared photodissociation
      spectroscopy from 800 to 4,000 cm-1.
AB  - The infrared spectra of protonated acetone and the proton bound acetone dimer are
      obtained revealing vibrational resonances associated with the shared proton
      motions, which are in agreement with the predictions from ab initio, MP2,
      harmonic frequency calculations.

PMID- 18075685
TI  - Hydrogen transfer from guest molecule to radical in adjacent hydrate-cages.
AB  - Electron spin resonance measurement of gamma-ray-irradiated propane hydrates
      shows that the normal propyl radical withdraws hydrogen from the adjacent propane
      molecule through the hexagonal planes of the hydrate cage without water molecule
      bridging.

PMID- 18075686
TI  - Experimental and theoretical study of the microsolvation of sodium atoms in
      methanol clusters: differences and similarities to sodium-water and sodium
      ammonia.
AB  - Methanol clusters are generated in a continuous He-seeded supersonic expansion
      and doped with sodium atoms in a pick-up cell. By this method, clusters of the
      type Na(CH(3)OH)(n) are formed and subsequently photoionized by applying a
      tunable dye-laser system. The microsolvation process of the Na 3s electron is
      studied by determining the ionization potentials (IPs) of these clusters size
      selectively for n = 2-40. A decrease is found from n = 2 to 6 and a constant
      value of 3.19 +/- 0.07 eV for n = 6-40. The experimentally-determined ionization
      potentials are compared with ionization potentials derived from quantum-chemical
      calculations, assuming limiting vertical and adiabatic processes. In the first
      case, energy differences are calculated between the neutral and the ionized
      cationic clusters of the same geometry. In the second case, the ionized clusters
      are used in their optimized relaxed geometry. These energy differences and
      relative stabilities of isomeric clusters vary significantly with the applied
      quantum-chemical method (B3LYP or MP2). The comparison with the experiment for n
      = 2-7 reveals strong variations of the ionization potential with the cluster
      structure indicating that structural diversity and non-vertical pathways give
      significant signal contributions at the threshold. Based on these findings, a
      possible explanation for the remarkable difference in IP evolutions of methanol
      or water and ammonia is presented: for methanol and water a rather localized
      surface or semi-internal Na 3s electron is excited to either high Rydberg or more
      localized states below the vertical ionization threshold. This excitation is
      followed by a local structural relaxation that couples to an autoionization
      process. For small clusters with n < 6 for methanol and n < 4 for water the
      addition of solvent molecules leads to larger solvent-metal-ion interaction
      energies, which consequently lead to lower ionization thresholds. For n = 6
      (methanol) and n = 4 (water) this effect comes to a halt, which may be connected
      with the completion of the first cationic solvation shell limiting the release of
      local relaxation energy. For Na(NH(3))(n), a largely delocalized and internal
      electron is excited to autoionizing electronic states, a process that is no
      longer local and consequently may depend on cluster size up to very large n.

PMID- 18075687
TI  - The hydration of glucose: the local configurations in sugar-water hydrogen bonds.
AB  - The hydration of a simple sugar is an essential model for understanding
      interactions between hydrophilic groups and interfacial water molecules. Here I
      perform first-principles molecular dynamics simulations on a glucose-water system
      and investigate how individual hydroxyl groups are locally hydrated. I
      demonstrate that the hydroxyl groups are less hydrated and more incompatible with
      a locally tetrahedral network of hydrogen bonds than previously thought. The
      results suggest that the hydroxyl groups form roughly two hydrogen bonds.
      Further, I find that the local hydration of the hydroxyl groups is sensitively
      affected by seemingly small variations in the local electronic structure and bond
      polarity of the groups. My findings offer insight into an atomic-level
      understanding of sugar-water interactions.

PMID- 18075688
TI  - Coupled-cluster methods with perturbative inclusion of explicitly correlated
      terms: a preliminary investigation.
AB  - We propose to account for the large basis-set error of a conventional coupled
      cluster energy and wave function by a simple perturbative correction. The
      perturbation expansion is constructed by Lowdin partitioning of the similarity
      transformed Hamiltonian in a space that includes explicitly correlated basis
      functions. To test this idea, we investigate the second-order explicitly
      correlated correction to the coupled-cluster singles and doubles (CCSD) energy,
      denoted here as the CCSD(2)(R12) method. The proposed perturbation expansion
      presents a systematic and easy-to-interpret picture of the "interference" between
      the basis-set and correlation hierarchies in the many-body electronic-structure
      theory. The leading-order term in the energy correction is the amplitude
      independent R12 correction from the standard second-order Moller-Plesset R12
      method. The cluster amplitudes appear in the higher-order terms and their effect
      is to decrease the basis-set correction, in accordance with the usual experience.
      In addition to the use of the standard R12 technology which simplifies all matrix
      elements to at most two-electron integrals, we propose several optional
      approximations to select only the most important terms in the energy correction.
      For a limited test set, the valence CCSD energies computed with the approximate
      method, termed , are on average precise to (1.9, 1.4, 0.5 and 0.1%) when computed
      with Dunning's aug-cc-pVXZ basis sets [X = (D, T, Q, 5)] accompanied by a single
      Slater-type correlation factor. This precision is a roughly an order of magnitude
      improvement over the standard CCSD method, whose respective average basis-set
      errors are (28.2, 10.6, 4.4 and 2.1%). Performance of the method is almost
      identical to that of the more complex iterative counterpart, CCSD(R12). The
      proposed approach to explicitly correlated coupled-cluster methods is technically
      appealing since no modification of the coupled-cluster equations is necessary and
      the standard Moller-Plesset R12 machinery can be reused.

PMID- 18075689
TI  - From nanostrips to nanorings: the elastic properties of gold-glued
      polyauronaphthyridines and polyacenes.
AB  - The previously proposed flat 2,6-diauro-1,5-naphthyridine polymers were bent to
      closed rings with up to 12 monomers. Their bending energies and lowest in-plane
      deformation frequencies were calculated at the DFT level using quasirelativistic
      pseudopotentials for gold. The ring-formation energies were compared with those
      for polyacene rings and found to be of the same order of magnitude, suggesting
      sufficient stability for the predicted polyauronaphthyridines. As function of the
      ring radius, r, the frequencies and deformation energies were shown to behave as
      r(-2) and r(-1), respectively. The molecules thus behave as classical elastic
      bodies.

PMID- 18075690
TI  - Dependence of charge transfer reorganization energy on carrier localisation in
      organic molecular crystals.
AB  - Taking the organic molecular material dithiophene-tetrathiafulvalene (DT-TTF) as
      an example of a high mobility organic molecular material, we use density
      functional calculations to calculate the dependency of the reorganization energy
      associated with charge carrier transport on: (i) the geometric and electronic
      responsiveness of the local molecular crystal environment, and, (ii) the local
      spatial extent of the charge carrier. We find that in our most realistic extended
      models the charge transfer reorganization energy is strongly dependent on carrier
      localization. In particular, whereas highly localized carriers are found to be
      highly susceptible to their charge transfer efficiency being affected by changes
      in the local crystal environment, more delocalized carriers are better able to
      maintain their low reorganization energies. Considering that maintaining a
      relatively small charge transfer reorganization energy magnitude is an important
      factor in achieving high carrier mobilities, we suggest that those materials
      better able to sustain carriers with short-range thermally resistant
      intermolecular delocalisation should be sought for device applications.

PMID- 18075692
TI  - Electronic spectra of radicals in a supersonic slit-jet discharge by degenerate
      and two-color four-wave mixing.
AB  - Four-wave mixing techniques have been used for the measurement of electronic
      transitions of cold transient species generated in a supersonic slit-jet
      discharge expansion. The origin band of the d(3)Pi(g)-a(3)Pi(u) system of C(2)
      and A(2)Pi(3/2)-X[combining tilde](2)Pi(3/2) electronic transition of HC(4)S were
      recorded. A signal-to-noise ratio of 10(4) in the spectra was achieved, resulting
      in detection limits of 10(10) cm(-3) for these two molecules. Application of
      selective two-color resonant four-wave mixing is used for the spectral assignment
      utilizing the double-resonance nature of the method. The combination of these
      techniques with a slit source proves to be a sensitive approach for the detection
      of transient molecules in a molecular beam discharge.

PMID- 18075691
TI  - The non-covalent functionalisation of carbon nanotubes studied by density
      functional and semi-empirical molecular orbital methods including dispersion
      corrections.
AB  - Density functional theory (DFT-D) and semi-empirical (PM3-D) methods having an
      added empirical dispersion correction have been used to study the binding of a
      series of small molecules and planar aromatic molecules to single-walled carbon
      nanotubes (CNTs). For the small molecule set, the PM3-D method gives a mean
      unsigned error (MUE) in the binding energies of 1.2 kcal mol(-1) when judged
      against experimental reference data for graphitic carbon. This value is close to
      the MUE for this method compared to high-level ab initio data for biological
      complexes. The PM3-D and DFT-D calculations describing the adsorption of the
      planar organic molecules (benzene, bibenzene, naphthalene, anthracene, TCNQ and
      DDQ) on the outer-walls of both semi-conducting and metallic CNTs give similar
      binding energies for benzene and DDQ, but do not display a stronger adsorption on
      [6,6] compared to [10,0] structures shown by another DFT study.

PMID- 18075693
TI  - Reactive uptake of acetic acid on calcite and nitric acid reacted calcite aerosol
      in an environmental reaction chamber.
AB  - The heterogeneous chemistry of gas-phase acetic acid with CaCO(3)(calcite)
      aerosol was studied under varying conditions of relative humidity (RH) in an
      environmental reaction chamber. Infrared spectroscopy showed the loss of gas
      phase reactant and the appearance of a gaseous product species, CO(2). The acetic
      acid is observed to adsorb onto the calcite aerosol through both a fast and a
      slow uptake channel. While the fast channel is relatively independent of RH, the
      slow channel exhibits enhanced uptake and reaction as the RH is increased. In
      additional experiments, the calcite aerosol was exposed to both nitric and acetic
      acids in the presence of water vapor. The rapid conversion of the particulate
      carbonate to nitrate and subsequent deliquescence significantly enhances the
      uptake and reaction of acetic acid. These results suggest a possible mechanism
      for observed correlations between particulate nitrate and organic acids in the
      atmosphere. Calcium rich mineral dust may be an important sink for simple organic
      acids.

PMID- 18075694
TI  - Photo-induced proton-transfer cycle of 2-naphthol in faujasite zeolitic
      nanocavities.
AB  - The excited-state deprotonation and ground-state reprotonation of a 2-naphthol
      molecule encapsulated in the zeolitic nanocavity of NaX have been studied by
      measuring static and time-resolved spectra of fluorescence and reflectance. The
      excited molecule undergoes enol dissociation within 300 ps to form an isolated
      ion pair, which undergoes geminate recombination in 1200 ps or separation to
      produce the anionic species of 2-naphtholate on the time scale of 2500 ps. Ground
      state reprotonation, controlled by the diffusion rate of a proton, is then
      followed in 0.8 ms with an activation energy of 13 kJ mol(-1).

PMID- 18075695
TI  - Niobium oxide-supported platinum ultra-low amount electrocatalysts for oxygen
      reduction.
AB  - We demonstrate a new approach to synthesizing high-activity electrocatalysts for
      the O(2) reduction reaction with ultra low Pt content. The synthesis involves
      placing a small amount of Pt, the equivalent of a monolayer, on carbon-supported
      niobium oxide nanoparticles (NbO(2) or Nb(2)O(5)). Rotating disk electrode
      measurements show that the Pt/NbO(2)/C electrocatalyst has three times higher Pt
      mass activity for the O(2) reduction reaction than a commercial Pt/C
      electrocatalyst. The observed high activity of the Pt deposit is attributed to
      the reduced OH adsorption caused by lateral repulsion between PtOH and oxide
      surface species. The new electrocatalyst also exhibits improved stability against
      Pt dissolution under a potential cycling regime (30,000 cycles from 0.6 V to 1.1
      V). These findings demonstrate that niobium-oxide (NbO(2)) nanoparticles can be
      adequate supports for Pt and facilitate further reducing the noble metal content
      in electrocatalysts for the oxygen reduction reaction.

PMID- 18075696
TI  - Dependence of surface stress, surface energy and surface tension on potential and
      charge.
AB  - A toy model and simple model functions are used to exemplify the relation between
      surface tension, surface energy and surface stress given by Shuttleworth's
      equation. Variations of the surface tension of charged interfaces must obey
      Lippmann's equation. Variations Deltaf of the surface stress of electrodes would
      be either equal to or proportional to and smaller than those variations
      Deltagamma of the surface tension, if the potential of zero charge (pzc) did not
      depend on the surface strain epsilon. However, since the pzc E(0) is a function
      of strain epsilon, the basic dependence of the surface stress on the charge,
      f(q), is described by a sum of three terms: the first one is the surface stress
      of the uncharged surface. The second one varies linearly with the surface
      tension, gamma(q), as long as the amount of specific adsorption remains constant,
      and is quadratic in E and q for a potential-independent double layer capacitance.
      The third summand that contributes to f(q) is linear in q and is a direct
      consequence of the potential dependence E(0)(epsilon) of the pzc. This result
      should help to resolve the seeming discrepancy between previous work on the
      surface stress changes of electrodes: Most experimental and theoretical results
      supported either the view that the variations of surface stress are identical or
      similar to that of surface tension, i.e. have essentially a quadratic dependence
      on the electrode potential, or that the basic dependence is a linear function of
      the charge. The more comprehensive model description presented here allows an
      explanation of the different results and their seeming discrepancies without
      assuming experimental errors or fundamental thermodynamic problems. Furthermore,
      an estimate of the potential dependence of the surface modulus can be obtained.

PMID- 18075697
TI  - The dynamics and orientation of a lipophilic drug within model membranes
      determined by 13C solid-state NMR.
AB  - Methods for determining how a drug interacts with cellular membranes at the
      molecular level can give valuable insight into the mode of action of the drug and
      its absorption, distribution and metabolism profile. A procedure is described
      here to determine the orientation and location of the lipophilic drug
      trifluoperazine (TFP) intercalated into dimyristoylphosphatidylcholine (DMPC)
      bilayers, by using a novel combination of high-resolution solid-state nuclear
      magnetic resonance (SSNMR) methods to observe signals from (13)C within the drug
      at natural abundance. SSNMR measurements of (1)H-(13)C dipolar couplings for TFP
      and selective broadening of (13)C NMR peaks by paramagnetic Mn(2+) together
      suggest a model for the location, orientation and dynamics of the drug within
      lipid bilayers that offers an explanation for the lysoprotective effect of the
      drug at low concentrations. The experiments described are straightforward to
      implement and can be used for the routine analysis of drug-membrane interactions
      to provide useful information for drug design and structure refinement.

PMID- 18075698
TI  - Investigation of entrance and exit effects on liquid transport through a
      cylindrical nanopore.
AB  - The entrance and exit effects on liquid transport through a nano-sized
      cylindrical pore under different solid wall-liquid interactions were studied by
      comparing molecular dynamics (MD) results of a finite length nanopore in a
      membrane with those of an infinite length one. The liquid transport through a
      finite length nanopore in a membrane was carried out by using a pressure-driven
      non-equilibrium molecular dynamics (NEMD) method proposed by Huang et al. [C.
      Huang, K. Nandakumar, P. Choi and L. W. Kostiuk, J. Chem. Phys., 2006, 124,
      234701]. The fluid motion through an infinite length nanopore, which had the same
      cross-stream dimension as the finite length channel in the membrane, but with
      periodic boundary conditions in the stream-wise direction, was carried out by
      using the external-field driven NEMD approach [J. Koplik, J. R. Bavanar and J. F.
      Willemsen, Phys. Rev. Lett., 1988, 60, 1282]. The NEMD results show that the
      pressure and density distributions averaged over the channel in the radial
      direction in both finite and infinite length channels are similar, but the radial
      distributions of the stream-wise velocity were significantly different when the
      solid wall was repulsive. The entrance and exit effects lead to a decrease in
      flow rate at about 39% for the repulsive wall and 6% for the neutral-like wall.

PMID- 18075699
TI  - Small angle X-ray scattering analysis of the effect of cold compaction of Al/MoO3
      thermite composites.
AB  - Nanothermites composed of aluminum and molybdenum trioxide (MoO(3)) have a high
      energy density and are attractive energetic materials. To enhance the surface
      contact between the spherical Al nanoparticles and the sheet-like MoO(3)
      particles, the mixture can be cold-pressed into a pelleted composite. However, it
      was found that the burn rate of the pellets decreased as the density of the
      pellets increased, contrary to expectation. Ultra-small angle X-ray scattering
      (USAXS) data and scanning electron microscopy (SEM) were used to elucidate the
      internal structure of the Al nanoparticles, and nanoparticle aggregate in the
      composite. Results from both SEM imaging and USAXS analysis indicate that as the
      density of the pellet increased, a fraction of the Al nanoparticles are
      compressed into sintered aggregates. The sintered Al nanoparticles lost contrast
      after forming the larger aggregates and no longer scattered X-rays as individual
      particles. The sintered aggregates hinder the burn rate, since the Al
      nanoparticles that make them up can no longer diffuse freely as individual
      particles during combustion. Results suggest a qualitative relationship for the
      probability that nanoparticles will sinter, based on the particle sizes and the
      initial structure of their respective agglomerates, as characterized by the mass
      fractal dimension.

PMID- 18075700
TI  - Anomalous reactivity of radical cations produced by photosensitized oxidation of
      4-methoxybenzyl alcohol derivatives: role of the sensitizer.
AB  - Steady-state and nanosecond laser flash photolysis measurements of 4
      methoxybenzyl alcohol (1a), 4-methoxy-alpha-methylbenzyl alcohol (1b), 4,4'
      dimethoxydiphenylmethanol (1c) and 4-methoxy-alpha,alpha'-dimethylbenzyl alcohol
      (1d) were carried out in air-equilibrated CH(2)Cl(2) and CH(3)CN solutions, in
      the presence of 9,10-dicyanoanthracene (DCA) and N-methylquinolinium
      tetrafluoroborate (NMQ(+)BF(4)(-)) as sensitizers. In particular, steady-state
      irradiation with DCA produced carbonyl compounds and, with NMQ(+)BF(4)(-),
      carbonyl compounds, ethers (substrates 1a-c ) and styrene (substrate 1d ) while
      time-resolved investigations gave evidence of charged species produced upon
      irradiation. The effect of solvent polarity on the reactivity was investigated;
      in the case of DCA, the reactivity increased with the solvent polarity, while the
      opposite was obtained when NMQ(+)BF(4)(-) was used. Quantum mechanical
      calculations at semiempirical (INDO/1-CI) and DFT (B3LYP/6-311G(d)) levels were
      used to support transient assignments and to obtain the charge and spin density
      distributions, respectively. The different photooxidation mechanisms operative
      with the neutral and charged sensitizer were rationalized in terms of the
      reactivity of free and complexed radical cations, respectively.

PMID- 18075701
TI  - Cold preservation of isolated hepatocytes in UW solution: experimental studies on
      the respiratory activity at 0 degrees C.
AB  - To date, little attention has been paid to the role of the gas milieu in
      preservation solutions and its effect on cell viability. Dissolved O2 in the
      preservation media may be an important parameter to consider. In this study we
      polarographically measured the O2 concentration in air-equilibrated UW solution
      at 0 degrees C, as well as the respiratory activity of isolated hepatocytes cold
      preserved in this solution up to 72 hours. To perform measurements at 0 degrees
      C, it was first necessary to characterize the sensor behavior at low
      temperatures. We verified that the sensor response is still linear at this
      temperature but the rate of response is significantly slower. The O2 solubility
      in UW-air solution at 0 degrees C was determined using a modified physical method
      and it was 410 microM O2, which, as expected, is lower than the solubility in
      water at the same temperature (453 microM O2). Isolated hepatocytes cold-stored
      in UW-air solution retained a measurable respiratory activity during a period of
      72 hours. The O2 consumption rate was 0.48 +/- 0.13 nmol/O2/min/10(6) cells,
      which represents 1% of the control value at 36 degrees C (61.46 +/- 14.61
      nmol/O2/min/10(6) cells). The respiratory activity and cell viability were well
      maintained during the preservation period. At present, preservation conditions
      need to be improved for cells to remain functionally active. Dissolved O2 may be
      required for energy re-synthesis but it also leads to an increment in reactive
      oxygen species. The O2 concentration in the preservation solution should be
      carefully controlled, reaching a compromise between cell requirement and
      toxicity.

PMID- 18075702
TI  - Regeneration of Dioscorea floribunda plants from cryopreserved encapsulated shoot
      tips: effect of plant growth regulators.
AB  - The encapsulation-dehydration protocol for the cryopreservation of in vitro shoot
      tips of Dioscorea floribunda was optimized. Maximum survival of 87% was obtained
      when overnight pretreatment with 0.3 M sucrose was followed by encapsulation,
      preculture in 0.75 M sucrose for 4 d, dehydration in a laminar air flow for 5.5
      h, quenching in liquid nitrogen and thawing at 40 degrees C. During recovery
      growth, 29% shoot formation was obtained when cryopreserved shoot tips were
      initially cultured for 25 d on a medium with 1.5 mg per liter (-1) BAP, 0.2 mg
      per liter(-1) NAA and 0.2 mg per liter(-1) GA3 followed by culturing for 15 d on
      a medium with reduced BAP (1 mg per liter(-1)) but increased NAA (0.5 mg per
      liter(-1)) and GA3 (0.3 mg per liter(-1)). Finally, transfer on to a medium with
      further reduced doses of BAP (0.05 mg per liter(-1)) and NAA (0.15 mg per liter(
      1)) but without GA3 stimulated production of fully grown plantlets. All plants
      regenerated without callus formation. Modification of post-thaw culture media
      with plant growth regulators was essential for regrowth of shoot tips to
      plantlets.

PMID- 18075703
TI  - Investigation of the influence of cell density of human fibroblasts cryopreserved
      inside collagen sponges at various cooling rates.
AB  - The influence of cell density of cells cryopreserved inside a collagen matrix at
      various cooling rates was investigated. Human fibroblasts were three
      dimensionally cultured for 2 days in a collagen sponge (20 mm in diameter and 1
      mm in thickness) as an extracellular matrix to imitate biological tissue
      (artificial tissue). Different cell densities for the artificial tissue were
      used, from 10(5) to 10(7) cells/cm(3). Four artificial tissues were first stacked
      in a test chamber, frozen at a cooling rate of 0.3 to 50 degrees C/min in a
      solution of Dulbecco's Modified Eagle Medium, 20% fetal bovine serum and 10%
      dimethylsulfoxide, kept frozen below -185 degrees C for 2 hours, and then finally
      thawed. Membrane integrity of fibroblasts using a trypan blue exclusion assay was
      evaluated as an index for post-thaw cellular viability. Results show that with
      increasing cell density, the post-thaw membrane integrity decreased. Therefore,
      in the cryopreservation of biological tissue, it seems high cell density is one
      factor which causes a decline in viability.

PMID- 18075704
TI  - Cold tolerance and overwintering of an introduced New Zealand frog, the brown
      tree frog (Litoria ewingii).
AB  - The overwintering strategy of Litoria ewingii in Otago, New Zealand, was studied
      under laboratory and field conditions. Microhabitat temperature measurements
      showed that the frogs were often exposed to subzero temperatures. In the
      laboratory, Litoria ewingii tolerated freezing for up to 6 hrs at -1 degrees C,
      and after the completion of the freezing event (about 1 hr) at -2 degrees C.
      Frogs frozen with insulation survived freezing for 12 hrs at -1 degrees C. Frogs
      supercooled to -1.2 +/- 0.1 degrees C and -1.7 +/- 0.3 degrees C on wet and dry
      substrates respectively. L. Ewingii tolerated up to 47.5% of its body water
      frozen. Plasma glucose levels and osmolality were not increased during freezing.
      It is concluded that l. Ewingii cannot avoid freezing and is sufficiently freeze
      tolerant to survive the subzero temperatures encountered during winter in Otago.

PMID- 18075705
TI  - The use of physical and virtual infrastructures for the validation of algal
      cryopreservation methods in international culture collections.
AB  - Two cryopreservation methods, colligative cryoprotection coupled with controlled
      cooling and vitrification-based, encapsulation-dehydration were validated by five
      members of the EU research infrastructure consortium, COBRA, and two independent
      external validators. The test strain Chlorella vulgaris SAG 211-11b was
      successfully cryopreserved using two-step cooling employing passive (Mr Frosty)
      and Controlled Rate Freezers (CRF) attaining the desired recovery target within
      15% of the median viability level (94%). Significant differences (p < 0.05)
      between cooling regimes were observed where Mr Frosty was more variable (Inter
      Quartile Range being 21.5%, versus 13.0% for CRF samples). Viability assessment
      using fluorescein diacetate gave significantly (P < 0.0001) higher survival than
      growth in agar with median values being 96% and 89%, respectively. On employing
      encapsulation-dehydration, greater variability between some validators was
      observed, with six labs observing recovery in 100% of the beads (84-95% of cells
      surviving) and one lab observing survival in 80% of the treated beads. Bead
      disruption followed by algal growth in agar was considered the most reliable and
      accurate method of assessing cell survival for encapsulation-dehydration.

PMID- 18075706
TI  - Field development of oil palms (Elaeis guineensis jacq) originating from
      cryopreserved stabilized polyembryonic cultures.
AB  - In this paper, the long term observation of plants originating from control and
      cryopreserved stabilized polyembryonic cultures (SPCs) of six elite oil palm
      clones was carried out. Survival of plantlets in the nursery was monitored, then
      a series of vegetative and floral characteristics of over 440 palms were studied
      for up to 12 years after field transfer in Cote D'Ivoire. The six clones tested
      showed an average recovery of 34% after freezing in liquid nitrogen. The average
      survival in the nursery of plantlets originating from pretreated and dehydrated
      and from cryopreserved SPCs was higher than that of control SPCs. Palm trees
      originating from control SPCs were found to flower earlier than those originating
      from pretreated and dehydrated and from cryopreserved SPCs. This delay in
      flowering disappeared progressively and all palms had flowered 3 years after
      planting regardless of the SPC treatment. Abnormal palms were observed in one
      clone only. With this clone, the percentage of abnormal palms originating from
      cryopreserved SPCs was significantly lower (5%) than that measured on palms
      originating from control SPCs (29%).

PMID- 18075707
TI  - Cryopreservation of embryonic axes of selected amaryllid species.
AB  - A study on cryopreservation of excised embryonic axes of fifteen species of the
      amaryllidaceae is reported. Embryonic axes that after flash-drying had a water
      content in the range 0.4 to 0.1 g/g and survival greater than 60% were selected
      for cryopreservation procedures. The highest post-thaw viabilities (roots and
      shoots produced) across all species were recorded for embryonic axes subjected to
      rapid rather than slow cooling. With rapid cooling and no cryoprotection, the
      highest post-thaw viabilities for the fifteen species investigated was 0% in one
      species; ranged between 10 and 35% for nine species; and between 45 and 55% for
      five species. With cryoprotection and rapid cooling the highest post-thaw
      viabilities for these fifteen species was 0% for one species; ranged between 15
      and 35% for six species; and between 40 and 75% for eight species. The highest
      post-thaw survival in ten out of fifteen species was obtained for axes dried to
      between 0.24 +/- 0.06 and 0.14 +/- 0.08 g/g(-1) (and rapidly cooled). With only
      one exception (Strumaria discifera; 45%), post-thaw survival after slow cooling
      ranged between 10 and 30%. Survival after vitrification plus slow cooling was
      achieved for seven species but was never higher than post-thaw survival in non
      cryoprotected, rapidly cooled axes. The results suggest that species within the
      same family can exhibit commonalities in terms of amenability to cryopreservation
      techniques but for maximum success, axis water content and cooling rate
      particularly, must be optimised for each species in the family independently.

PMID- 18075708
TI  - Suicide by charcoal burning in Taiwan: implications for means substitution by a
      case-linkage study.
AB  - OBJECTIVE: This study estimated the incidence of suicide mortality among suicide
      attempters in Taiwan and assessed the extent of means substitution among subjects
      with a non-fatal attempt and a subsequent fatal attempt during the study period.
      METHODS: A total of 5,261 suicide attempters registered in a surveillance system
      of a metropolitan catchment area from 2004 to 2005 were followed through 2005.
      Linkage to the death certification system revealed that 72 died by suicide. The
      association of completed suicide with the suicide method used at index attempt
      was examined using Cox proportional hazards regression. Incidence rate for the
      subsequent lethal suicide was estimated based on life tables. RESULTS: The 1-year
      incidence rate of suicide mortality was 0.017: 0.026 in males and 0.013 in
      females. There was a strong association between burning charcoal as the method
      used at the index attempt (relative hazard = 4.1, P < 0.001) and completed
      suicides. Those who used the method of burning charcoal at the index attempt
      frequently used the same means in a subsequent attempt leading to suicide
      mortality. However, a majority of suicide completers (59.1%) who died by burning
      charcoal had used a different method at their index attempt. CONCLUSIONS: Persons
      who attempt suicide by charcoal burning are a high-risk group for completed
      suicide. Those who burned charcoal in a suicide attempt were likely to use the
      same method in a later lethal attempt, and charcoal burning was a frequent cause
      of death among those who used different methods in earlier attempts. Charcoal
      burning should be a target for suicide prevention efforts.

PMID- 18075709
TI  - Psychopathology in adolescent and young adult criminal offenders (15-21 years) in
      Sweden.
AB  - BACKGROUND: This study examined rates of psychopathology among adolescent and
      young adult serious offenders referred to pre-sentence forensic psychiatric
      services and compared patterns of psychiatric morbidity with adult forensic
      referrals and age-matched general psychiatric inpatients. METHODS: In Sweden,
      criminal offenders can be referred for an extensive court-ordered pre-sentence
      inpatient forensic psychiatric examination (FPE). Data on all 3,058 of these
      offenders (90% male, mean age = 35.3 years) during 1997-2001 were obtained from
      the National Board of Forensic Medicine. We compared DSM-IV psychiatric diagnoses
      across age bands 15-17 years (N = 60), 18-21 years (N = 300) and 22 years and
      older (N = 2,698). Comparative data by age bands were also obtained for inpatient
      diagnoses among individuals admitted to general psychiatric hospitals. RESULTS:
      Compared with the adult forensic psychiatric examinees, those aged 15-17 years
      and 18-21 years had higher rates of depression, and childhood and developmental
      disorders but lower rates of psychosis, bipolar disorder, and substance use
      disorders. Compared with general psychiatric inpatients, offenders aged 15-17
      years had higher prevalences of depression and attention-deficit or disruptive
      disorders and lower ones of alcohol and drug misuse disorders. CONCLUSIONS: There
      are significant differences in patterns of psychiatric morbidity in adolescent
      and young adult offenders that come into contact with psychiatric services
      compared with older offenders and adolescent psychiatric inpatients. This
      suggests that the development of health services addressing the psychiatric needs
      of younger offenders needs to draw on information on their specific mental health
      needs.

PMID- 18075710
TI  - Evidence of increased diversity of methanogenic archaea with plant extract
      supplementation.
AB  - This study evaluated the effects of selected essential oils on archaeal
      communities using the ovine rumen model. Forty weaned Canadian Arcott ewes, fed
      with barley-based diet, were allotted to one of three essential oil
      supplementation treatments or a control (10 ewes per treatment) for 13 weeks. The
      treatments were cinnamaldehyde, garlic oil, juniper berry oil, and a control with
      no additive. Rumen content was sampled after slaughter and grouped by treatment
      by combining subsamples from each animal. DNA was extracted from the pooled
      samples and analyzed for methanogenic archaea using quantitative polymerase chain
      reaction, denaturing gradient gel electrophoresis, cloning, and sequencing. Our
      results suggest that the total copy number of archaeal 16S rRNA was not
      significantly affected by the treatments. The phylogenetic analysis indicated a
      trend toward an increased diversity of methanogenic archaea related to
      Methanosphaera stadtmanae, Methanobrevibacter smithii, and some uncultured groups
      with cinnamaldehyde, garlic, and juniper berry oil supplementation. The trends in
      the diversity of methanogenic archaea observed with the essential oil
      supplementation may have resulted from changes in associated protozoal species.
      Supplementation of ruminant diets with essential oils may alter the diversity of
      rumen methanogens without affecting the methanogenic capacity of the rumen.

PMID- 18075711
TI  - Sex-specific Tyrian purple genesis: precursor and pigment distribution in the
      reproductive system of the marine mollusc, Dicathais orbita.
AB  - Exploitation of Tyrian purple from muricid molluscs, since antiquity, has
      prompted much interest in its chemical composition. Nevertheless, there remains a
      paucity of information on the biosynthetic routes leading to observed sexual
      differences in pigmentation. A liquid chromatography-mass spectrometry (LQ-MS)
      method was developed to simultaneously quantify dye pigments and precursors in
      male and female Dicathais orbita. The prochromogen, tyrindoxyl sulfate, was
      detected for the first time, by using this method in hypobranchial gland extracts
      of both sexes. Intermediates tyrindoxyl, tyrindoleninone, and tyriverdin were
      detected in female hypobranchial glands, along with 6,6'-dibromoindigo, while
      males contained 6-bromoisatin and 6,6'-dibromoindirubin. Multivariate analysis
      revealed statistically significant differences in the dye composition of male and
      female hypobranchial glands (ANOSIM, P = 0.002), thus providing evidence for sex
      specific genesis of Tyrian purple in the Muricidae. Dye precursors were also
      present in male and female gonoduct extracts, establishing a mechanism for the
      incorporation of bioactive intermediates into muricid egg masses. These findings
      provide a model for investigating sex-specific chemical divergences in marine
      invertebrates and support the involvement of Tyrian purple genesis in muricid
      reproduction.

PMID- 18075712
TI  - TNF-alpha blockade induces a reversible but transient effect on endothelial
      dysfunction in patients with long-standing severe rheumatoid arthritis.
AB  - Considerable evidence indicates that patients with rheumatoid arthritis (RA) are
      at greater risk of developing atherosclerosis and cardiovascular disease. Recent
      studies support the predictive ability of endothelial function measures for
      subsequent atherosclerotic events. We have investigated the effects of
      infliximab, a chimeric monoclonal anti-tumor necrosis factor (TNF) antibody, on
      endothelial vasodilation, measured by brachial ultrasonography and on the levels
      of inflammatory biomarkers and adhesion molecules in ten consecutive patients
      with severe long-standing RA, despite methotrexate therapy, during the loading
      phase of infliximab therapy. Flow-mediated dilation (FMD) in RA patients at
      baseline was significantly impaired compared with healthy controls (7.71 +/-
      2.78% vs 14.91 +/- 6.41%; p = 0.008) and improved significantly after infliximab
      infusion (12.63 +/- 1.63% vs 7.71 +/- 2.78%; p = 0.005). At baseline, a
      statistically significant correlation between C-reactive protein levels and FMD
      was found (r = -0.69, p = 0.026). However, this improvement was transitory, as
      FMD values returned to baseline values before each infliximab infusion at weeks
      2, 6 and 14. There were no significant differences in baseline brachial artery
      diameter between visits, although at each time, the diameter was increased.
      According to European League Against Rheumatism response criteria, all ten
      patients were good responders. No significant differences were observed in
      intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1,
      vascular endothelial growth factor and E-selectin plasma levels before and after
      each infusions. This study demonstrates that endothelial dysfunction is a
      reversible phenomenon in RA. The addition of anti-TNFalpha treatment reduces
      inflammatory symptoms in patients with severe RA. The improvement of endothelial
      function during the loading phase of therapy is transitory, suggesting an
      enhanced and persistent TNF-alpha generation within the arterial wall.

PMID- 18075713
TI  - Bias, reporting, and sharing: computational evaluations of docking methods.
AB  - Computational methods for docking ligands to protein binding sites have become
      ubiquitous in drug discovery. Despite the age of the field, no standards have
      been established with respect to methodological evaluation of docking accuracy,
      virtual screening utility, or scoring accuracy. There are critical issues
      relating to data sharing, data set design and preparation, and statistical
      reporting that have an impact on the degree to which a report will translate into
      real-world performance. These issues also have an impact on whether there is a
      transparent relationship between methodological changes and reported performance
      improvements. This paper presents detailed examples of pitfalls in each area and
      makes recommendations as to best practices.

PMID- 18075715
TI  - [Candidate selection in internal medicine regarding the new licensing regulation
      for doctors].
AB  - BACKGROUND AND PURPOSE: Since October 2003, a new licensing regulation for
      doctors exists in Germany. Due to this reform medical students obtain individual
      grades for each clinical subject. At the end of 2006, these grades appeared in
      the students' leaving certificates for the first time. As the significance of
      these grades concerning their influence on selection criteria is still very
      uncertain, the aim of this study was to further investigate criteria for
      residency selection focusing on the evaluation of the new grades. METHODS: The
      importance of selection criteria was assessed by an electronic questionnaire
      based on a five-point Likert scale (1 = unimportant; 5 = critical). The
      questionnaire was sent to 7,766 members of the German Society of Internal
      Medicine in May 2006. 897 questionnaires were returned (11.6%): 133 heads of
      department, 158 senior physicians, 269 specialists, and 337 residents. 43% of the
      respondents were involved in the selection process. RESULTS: Factors ranking as
      most important for respondents involved in residency selection included
      personally knowing an applicant, e.g., after a rotation (mean 4.1; standard
      deviation 1.3), and personal recommendations from colleagues (3.8 +/- 1.2). High
      emphasis was also placed on social commitment and additional skills. Concerning
      the grades given according to the old licensing regulation for doctors, the final
      grade of the Medical Licensing Examination (3.5 +/- 1.1) and the grade of the
      Medical Licensing Examination step 3 (3.4 +/- 1.1) were ranked as important.
      Regarding the new licensing regulation for doctors, 38% of the respondents (3.0
      +/- 1.2) considered the individual grades more important than the results of the
      Medical Licensing Examination step 2. 49% of the respondents stated, that the
      grade D ("sufficient") in internal medicine would be an exclusion criterion when
      selecting residents (3.3 +/- 1.3). CONCLUSION: Whether the results are
      representative of all physicians involved in the selection process has to remain
      open taking a response rate of 11.6% into account. Personal knowledge of
      applicants, personal recommendations and additional skills were considered more
      important than the grades in the Medical Licensing Examination when selecting
      residents. The new individual grades were evaluated heterogeneously, but there is
      a tendency toward ranking the grades of their own clinical subject as important;
      especially minor grades are considered an exclusion criterion.

PMID- 18075714
TI  - A new artificial chaperone for protein refolding: sequential use of detergent and
      alginate.
AB  - A novel artificial chaperone system using a combination of detergents and
      alginate was developed to refold three enzymes with totally different structures.
      Upon dilution of denatured protein 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 gradually remove the detergent molecules. In that
      respect, we used alginate, a linear copolymer of D-mannuronic acid and L
      guluronic acid, to initiate and complete the refolding process. The results
      indicated that the extent of refolding assistance for the proteins was different
      due to detergent structure and also the length of hydrophobic portion of each
      detergent. These observed differences were attributed to the strong electrostatic
      and hydrophobic interactions among the capturing and stripping agents used in
      this investigation. Based on this newly developed method, it is expected that the
      protein refolding operation can be achieved easily, cheaply and efficiently.

PMID- 18075716
TI  - [Antibiotic drug-resistant tuberculosis].
AB  - Tuberculosis remains to be one of the most important infectious diseases
      worldwide. Among the estimated 9 million new cases that are anually recorded,
      antibiotic drug resistance of Mycobacterium tuberculosis has become an increasing
      problem. Cases of multidrug resistance (MDR), by definition resistance against at
      least isoniazid and rifampin, are reported worldwide. Moreover, cases of
      extensively drug-resistant tuberculosis (XDR-TB) with additional resistance to
      fluoroquinolones and aminoglycosides are also emerging. Patients who are infected
      with MDR-TB strains need a carefully selected antibiotic combination therapy
      consisting of four to six alternative drugs according to the results of in vitro
      drug susceptibility testing. The duration of treatment against MDR-TB is cost
      intensive, and is generally recommended for 18 months beyond the first time of
      sustained culture negativity. Patient adherence to the therapy is essential. As
      adverse effects of MDR-TB therapy are common, treatment of these patients should
      be guided by experienced physicians.

PMID- 18075717
TI  - [Psychosocial risk factors for cancer development].
AB  - Cancer is one of the most frequent causes of death in Germany. The reasons of
      various cancer diseases still remain uncertain. There is a long-standing
      discussion about associations between personality, depression, stress, and
      stressful life events, respectively, and the development of malignant neoplasms.
      Evidence for a role of psychosocial factors in development of cancer is not
      unequivocal despite many years of research on the subject. Current prospective
      investigations do not support the conventional wisdom of a direct influence for
      personality in the development of cancer. Much of the research has been impaired
      by methodological flaws such as inadequate sample size, failure to adjust for
      potential confounders, lengths of follow-up, use of a variation of different
      measurements of cancer, and psychosocial variables. Furthermore, specific
      personality traits and various life events are associated with certain health
      related behavior and lifestyle factors, e.g., smoking or an unhealthy nutrition.
      These unhealthy habits can increase cancer risk. Psychological parameters may
      alter immune and endocrine function and it has long been hypothesized that,
      through this pathway, psychosocial factors may affect cancer incidence. In
      conclusion, study results to substantiate the role of psychosocial factors in the
      development of various cancers are inconclusive. Contradictory results may be
      explained by methodological shortcomings. Further studies are required to pursue
      this question further.

PMID- 18075718
TI  - [Non-small cell lung cancer - diagnostics and stage-adapted therapy].
AB  - Non-small cell lung cancer is a common disease. Adeno- and squamous-cell type are
      the most frequent subtypes, the former with rising incidence. The clinical
      picture is nonspecific until late in the course of the disease. The most
      important diagnostic tools are chest X-ray, computed tomogram of the chest, and
      bronchoscopy. Additional tests often used for staging are abdominal ultrasound,
      computed tomography of the abdomen, bone scintigraphy, and magnetic resonance
      imaging of the head. Positron emission tomography is of rising importance.
      Therapy is guided by stage. Stage I disease is a domain of surgery, in stage II
      combined with adjuvant chemotherapy. In stage III, multimodality treatment,
      mostly chemoradiotherapy, is indicated. Stage IV disease is treated with
      palliative chemotherapy. Newer, so-called targeted therapies are more and more
      implemented into therapy. There are three substances approved for second-line
      therapy with response rates of just under 10%.

PMID- 18075719
TI  - [CME activities of medical journals: quality of multiple-choice questions as
      evaluation tool. Using the example of the German medical journals Deutsches
      Arzteblatt, Deutsche Medizinische Wochenschrift, and Der Internist].
AB  - BACKGROUND AND PURPOSE: The participation of doctors in Continuing Medical
      Education (CME) activities provided by medical journals increases. Therefore,
      their quality and efficacy need to be evaluated. METHODS: This study evaluated
      the quality of the multiple-choice questions (MCQs) as evaluation tool of CME
      activities in three German medical journals (Der Internist, Deutsches Arzteblatt,
      Deutsche Medizinische Wochenschrift). In total, 390 MCQs were reviewed using
      evidence-based principles of effective item writing. The content quality of the
      MCQs was not evaluated in this study. RESULTS: 264 (67.7%) of 390 MCQs contained
      flaws with 449 flaws in total. The proportion of flawed items was 60.8% in
      Deutsches Arzteblatt, 63.3% in Der Internist, and 77.9% in Deutsche Medizinische
      Wochenschrift. The most frequent flaws were clues (33.8%, Deutsches Arzteblatt),
      negatively worded stems (29.8%, Der Internist), and unfocused stems (24.7%,
      Deutsche Medizinische Wochenschrift). SCHLUSSFOLGERUNG: The problem of formal
      flaws in MCQs has an extensive relevance, as seen by the large number of studies
      related to this topic. The frequency of flaws (67.7%) was similar to recent
      studies. The distribution of the flaws suggests that with minor editing the
      quality of the MCQs could be substantially improved. PERSPECTIVE: The use of high
      quality evaluation tools is essential to invalidate the accusation of the
      trivialization of CME activities, irrespective of their social context.

PMID- 18075720
TI  - [AV Shunt: a rare cause of cardiac decompensation].
AB  - HISTORY AND PHYSICAL EXAMINATION: A 66-year-old man presented with signs of heart
      failure for the first time. Apart from a history of arterial hypertension for
      several years, no relevant disease was known so far. The initial physical
      examination revealed symptoms of right heart failure and an elevated systolic
      blood pressure. INVESTIGATIONS: X-ray of the chest showed an enlarged heart
      shadow and no definite signs of pulmonary congestion. Echocardiography revealed a
      dilated left ventricle (left ventricular end-diastolic diameter 59 mm) with
      moderately reduced contractility (ejection fraction 35%). Laboratory parameters
      were normal. An invasive investigation of the reduced contractility was prepared.
      DIAGNOSIS, THERAPY, AND COURSE: While measuring blood pressure, a murmur and a
      little scar in the left elbow flexure were discovered. The suspicion of a
      traumatic arteriovenous fistula after a mirror glass injury 8 years ago was
      confirmed by sono- and angiography. The shunt volume was calculated by oxymetry
      as 6.2 l/min. The fistula was surgically dissected and ligated. At follow-up 1
      year later, the patient reported no complaints and showed good exercise capacity.
      Echocardiography revealed normal parameters. CONCLUSION: This case demonstrates
      the reversibility of high-output heart failure after treatment of the underlying
      cause. It stresses the importance of careful interrogation and examination of the
      patient. Apparently obvious causal connections must be thoroughly worked up and
      critically questionned.

PMID- 18075721
TI  - [DRG and coding: sleep-related breathing disorders].

PMID- 18075722
TI  - [Endocarditis Libman-Sacks in case of systemic lupus erythematosus (SLE). A rare
      reason for acquired high-grade aortic valve insufficiency].

PMID- 18075723
TI  - [How to recognize a strong heart - answers from ancient philosophy].

PMID- 18075724
TI  - Awake craniotomy for monitoring of language function: benefits and limits.

PMID- 18075725
TI  - Report of the JRAAC on the situation of the accreditation Training Programmes in
      Europe.

PMID- 18075727
TI  - Identification of defense-related genes in rice responding to challenge by
      Rhizoctonia solani.
AB  - Rice sheath blight, caused by Rhizoctonia solani is one of the major diseases of
      rice. The pathogen infects rice plants directly through stomata or using lobate
      appressoria and hyphal masses called infection cushions. The infection structures
      were normally found at 36 h post-inoculation. During infection, the pathogenesis
      related genes, PR1b and PBZ1 were induced in rice plants. To identify rice genes
      induced early in the defense response, suppression subtractive hybridization
      (SSH) was used to generate a cDNA library enriched for transcripts differentially
      expressed during infection by R. solani. After differential screening by membrane
      based hybridization and subsequent confirmation by reverse Northern blot
      analysis, selected clones were sequenced. Fifty unique cDNA clones were found and
      assigned to five different functional categories. Most of the genes were not
      previously identified as being induced in response to pathogens. We examined
      expression of 100 rice genes induced by infection with Magnaporthe grisea,
      Xanthomonas oryzae pv. oryze (Xoo) and X. oryzae pv. oryzicola (Xooc). Twenty
      five of them were found to be differentially expressed after the sheath blight
      infection, suggesting overlap of defense responses to different fungal and
      bacterial pathogens infection.

PMID- 18075728
TI  - Zero erucic acid trait of rapeseed (Brassica napus L.) results from a deletion of
      four base pairs in the fatty acid elongase 1 gene.
AB  - The fatty acid elongase 1 (FAE1) gene is a key gene in the erucic acid
      biosynthesis in rapeseed. The complete coding sequences of the FAE1 gene were
      isolated separately from eight high and zero erucic acid rapeseed cultivars
      (Brassica napus L.). A four base pair deletion between T1366 and G1369 in the
      FAE1 gene was found in a number of the cultivars, which leads to a frameshift
      mutation and a premature stop of the translation after the 466th amino acid
      residue. This deletion was predominantly found in the C-genome and rarely in the
      A-genome of B. napus. Expression of the gene isoforms with the four base pair
      deletion in a yeast system generated truncated proteins with no enzymatic
      activity and could not produce very long chain fatty acids as the control with an
      intact FAE1 gene did in yeast cells. In the developing rape seeds the FAE1 gene
      isoforms with the four base pair deletion were transcribed normally but failed to
      translate proteins to form a functional complex. The four base pair deletion
      proved to be a mutation responsible for the low erucic acid trait in rapeseed and
      independent from the point mutation reported by Han et al. (Plant Mol Biol 46:229
      239, 2001).

PMID- 18075729
TI  - [Diagnosis and therapy of osteogenesis imperfecta].
AB  - Osteogenesis imperfecta (OI) is a congenital connective tissue disorder with an
      incidence of up to 1:30,000. Patients suffer from deformities and fractures, and
      many of them never reach ambulation. The therapy consists of conservative,
      medicamentous and operative procedures that are described in this article.

PMID- 18075730
TI  - In vitro validation of a novel method for continuous intra-abdominal pressure
      monitoring.
AB  - OBJECTIVE: Intra-abdominal pressure (IAP) measurement is important in daily
      clinical practice. Most measurement techniques vary in automaticity and
      reproducibility. This study tested a new fully automated continuous technique for
      IAP measurement, the CiMON. METHODS: Three IAP measurement catheters (a Foley
      manometer and two balloon-tipped catheters) contained in a 50-ml infusion bag
      were placed on the bottom of a half open 3-l container. To simulate IAH the
      container was filled with water using 5 cmH2O increments (0-30 cmH2O). Pressure
      was estimated by observers using the Foley manometer (IAP(FM)) and simultaneously
      recorded using two IAP monitors: IAP(spie) with Spiegelberg and IAP(CiM) with
      CiMON. Observers were blinded to the reference levels. Fifteen observers (three
      intensivists, four residents, two medical students, and six nurses) conducted
      three pressure readings at each of the seven pressure levels with the FM
      technique, giving 315 readings. These were paired with the automated IAP(spie)
      and IAP(CiM) readings and the height of the H2O column. RESULTS: The intra- and
      interobserver coefficients of variation (COVA) were low for all methods. There
      was no difference in the results between specialists, physicians in training,
      andnurses. Spearman's correlation coefficient (R2) values for all paired
      measurements were greater than 0.9, and Bland-Altman analysis comparing the
      reference H2O column, IAP(FM), and IAP(spie) to IAP(CiM) showed a very good
      agreement at all pressure levels (bias -0.1+/-0.6 cmH2O, 95%CI -0.2 to 0). There
      was a consistent, low underestimation of the reference H2O pressure by the
      Spiegelberg technique and a low overestimation at pressures below 20 cmH2O by
      both other techniques. CONCLUSIONS: All three measurement techniques, IAP(FM),
      IAP(spie), and IAP(CiM) have good agreement with the applied hydrostatic pressure
      in this in vitro model of IAP measurement.

PMID- 18075731
TI  - Considerations about the knee arthrography for detection of meniscal tears.

PMID- 18075732
TI  - To recycle or not to recycle? An intergenerational approach to nuclear fuel
      cycles.
AB  - This paper approaches the choice between the open and closed nuclear fuel cycles
      as a matter of intergenerational justice, by revealing the value conflicts in the
      production of nuclear energy. The closed fuel cycle improve sustainability in
      terms of the supply certainty of uranium and involves less long-term radiological
      risks and proliferation concerns. However, it compromises short-term public
      health and safety and security, due to the separation of plutonium. The trade
      offs in nuclear energy are reducible to a chief trade-off between the present and
      the future. To what extent should we take care of our produced nuclear waste and
      to what extent should we accept additional risks to the present generation, in
      order to diminish the exposure of future generation to those risks? The advocates
      of the open fuel cycle should explain why they are willing to transfer all the
      risks for a very long period of time (200,000 years) to future generations. In
      addition, supporters of the closed fuel cycle should underpin their acceptance of
      additional risks to the present generation and make the actual reduction of risk
      to the future plausible.

PMID- 18075733
TI  - On the relation between 2D:4D and sex-dimorphic personality traits.
AB  - Several personality traits, including aggressiveness and sensation seeking, have
      been hypothesized to be influenced by prenatal androgen exposure, though evidence
      for this proposition is limited. We investigated whether individual differences
      in aggressiveness, sensation seeking, and several prosocial personality traits
      can be predicted from differences in the 2D:4D digit ratio, a putative marker of
      prenatal androgen activity. A total of 164 undergraduates (87 men, 77 women)
      completed self-report measures of physical and verbal aggression, as well as a
      standardized measure of sensation seeking, and five scales to assess empathy,
      nurturance, expressivity/femininity, instrumentality/masculinity, and
      assertiveness. Two sex-dimorphic tests of spatial ability also were included. Men
      had a lower 2D:4D ratio than women, confirming the typical sex difference in
      digit proportions. Significant sex differences were observed on 10 of the 11
      personality scales purported to show sex differences and on both tests of spatial
      ability. The 2D:4D ratio was a significant predictor of scores on three of the
      four aggression subscales, total aggression, thrill and adventure seeking, and
      total sensation-seeking, in the sample as a whole and in women. In men,
      correlations with 2D:4D were significant only for total sensation-seeking and
      verbal aggression. In both sexes, lower 2D:4D ratios were associated with
      increased aggressiveness and sensation seeking. For the spatial tests, there was
      no evidence of any association with 2D:4D in either men or women. The 2D:4D digit
      ratio may be a valid, though weak, predictor of selective sex-dependent traits
      that are sensitive to testosterone.

PMID- 18075734
TI  - Acute treatment with low doses of memantine does not impair aversive, non
      associative and recognition memory in rats.
AB  - Memantine is a non-competitive N-methyl-d-aspartate receptor antagonist, which
      has been employed in the clinic as a neuroprotective agent for the treatment of
      several dementias, particularly Alzheimer's disease. In this study, we evaluated
      pharmacological effects of the acute administration of memantine on memory
      process. Memory retention scores were evaluated in normal adult Wistar rats
      injected with saline and memantine (2, 5, 10, and 20 mg/kg, IP) and then
      subjected to the step-down inhibitory avoidance task, habitation to an open-field
      apparatus, and object recognition task. The treatment with higher doses of
      memantine (10 and 20 mg/kg) injected 60 min before or immediately after training
      session impaired acquisition and retention of aversive memory in the inhibitory
      avoidance task. In addition, higher doses of memantine injected 60 min before the
      first open-field exposure also impaired habituation during the second exposure to
      the apparatus. No significant differences were observed in the performance of
      rats treated with memantine, in all doses tested, compared to saline-treated rats
      in the object recognition task. Notably, we observed that at 5 mg/kg, memantine
      increased spontaneous locomotion and exploration in the rat open-field test. In
      conclusion, present findings support the view that memantine at lower doses did
      not affect memory formation in normal rats, but at high doses memantine, induce
      hyperlocomotion, which could bias the interpretation of the animal behavior
      assessed in memory tests.

PMID- 18075737
TI  - (18)F-FDG uptake at vaccination site.

PMID- 18075736
TI  - Drug-eluting coronary stents: as safe as bare-metal stents, but optimized
      antiplatelet therapy may further improve clinical outcome.

PMID- 18075738
TI  - Bone scintigraphy in electrocution wounds and comparison with FDG-PET images.

PMID- 18075739
TI  - Androgen receptor expression in prostate cancer stem cells: is there a conundrum?
AB  - Androgen deprivation therapy (ADT) is standard frontline therapy for metastatic
      prostate cancer. However, prostate cancer progresses to a castrate-resistant
      state. The response of prostate cancer to androgen deprivation is mediated by the
      androgen receptor (AR). Castrate-resistant disease is marked by a gain-of
      function in AR and AR reactivation. The stem cell hypothesis of cancer would
      therefore predict that AR should be expressed in the prostate cancer stem cell,
      since genetic selection for gain-of-function changes in AR, such as AR gene
      amplification, should occur at the level of the stem cell population. Initial
      reports characterizing prostate cancer stem cells suggest that AR is not
      expressed in this population, which is an apparent conundrum. Here, we examined
      the CD44+/24- LNCaP putative stem cell population by in-cell Western and show
      that AR is expressed at the protein level. Our findings suggest that at least a
      subset of prostate cancers express AR in the putative stem cell population.

PMID- 18075740
TI  - Pretreatment with 5-FU enhances cisplatin cytotoxicity in head and neck squamous
      cell carcinoma cells.
AB  - PURPOSE: In the treatment of head and neck malignancy, cisplatin and 5-FU have
      been used the most as chemotherapeutic agents. The difference in efficacies of
      these is unclear and controversial. To investigate more effective schedule, we
      analyzed the cytotoxicity in different treatment sequence with two agents in
      vitro and the mechanism for different effectiveness. METHODS: UM-SCC-23 and UM
      SCC-81B, head and neck squamous cell carcinoma cell lines, were analyzed for
      cellular killing in alternative sequence treatment with cisplatin and 5-FU. The
      treatment schedule was designed based on the clinical regimen. To determine the
      mechanism for the difference of cytotoxicity with each schedule, cell cycle
      distributions of both cells after 5-FU treatment with various durations were
      analyzed by flow-cytometry and immunostaining with anti-PCNA and anti-BrdU.
      RESULTS: 5-FU pretreatment followed by cisplatin treatment showed higher cell
      killing in both types of cells than the reverse treatment schedule. In the cell
      cycle analysis and immunostaining after the treatment of 5-FU, the rate of PCNA
      positive cells was increased from 24 to 144 h in both cells. The rate of BrdU
      positive cells of UM-SCC-81B in flow-cytometry was also increased, while that of
      UM-SCC-23 was gradually decreased. These data suggested that the cells treated
      with 5-FU for more than 144 h were still in the S-phase with or without DNA
      synthesis. CONCLUSIONS: In head and neck carcinoma cells, we showed 5-FU
      pretreatment enhanced cisplatin cytotoxicity. The result of cell cycle analysis
      and immunostaining showed S-phase arrest by treatment of prolonged 5-FU
      treatment. The very long arrest in S-phase might be a mechanism to enhance
      cisplatin cytotoxicity by 5-FU pretreatment. We thus suggest pretreatment with 5
      FU to enhance the effectiveness of cisplatin-based chemotherapy.

PMID- 18075741
TI  - The imbalance between osteoprotegerin and cathepsin K in the serum of patients
      with longstanding rheumatoid arthritis.
AB  - Osteoprotegerin (OPG) and soluble receptor activator of NF-kappa B ligand
      (sRANKL) together regulate the bone metabolism among other cytokines, whereby
      cathepsin K has a potent collagen-degrading activity. An imbalance of this system
      may be partly responsible for the skeletal complications of RA. Expanding on a
      previous study, we investigated the relationship between OPG, sRANKL and
      cathepsin K levels in the serum of patients with longstanding RA. We measured
      serum levels of OPG, sRANKL and cathepsin K of 100 patients with active,
      longstanding RA. We detected elevated serum levels of cathepsin K (median 54.8
      pmol/l) and OPG (median 4.8 pmol/l), but normal sRANKL levels (median 0.2
      pmol/l). Cathepsin K did not show a correlation with the overexpressed OPG
      (P=0.64) and sRANKL (P=0.81). The radiological destruction correlates
      significantly with cathepsin K (P=0.004) and OPG (P=0.007). We speculate that the
      increased levels of OPG are effective in compensating the action of sRANKL, but
      do not directly prevent bone degradation, as reflected by the elevated serum
      levels of cathepsin K.

PMID- 18075742
TI  - Prospective navigator-echo-based real-time triggering of fetal head movement for
      the reduction of artifacts.
AB  - The purpose of this study was to evaluate the neuroimaging quality and accuracy
      of prospective real-time navigator-echo acquisition correction versus untriggered
      intrauterine magnetic resonance imaging (MRI) techniques. Twenty women in whom
      fetal motion artifacts compromised the neuroimaging quality of fetal MRI taken
      during the 28.7 +/- 4 week of pregnancy below diagnostic levels were additionally
      investigated using a navigator-triggered half-Fourier acquired single-shot turbo
      spin echo (HASTE) sequence. Imaging quality was evaluated by two blinded readers
      applying a rating scale from 1 (not diagnostic) to 5 (excellent). Diagnostic
      criteria included depiction of the germinal matrix, grey and white matter, CSF,
      brain stem and cerebellum. Signal-difference-to-noise ratios (SDNRs) in the white
      matter and germinal zone were quantitatively evaluated. Imaging quality improved
      in 18/20 patients using the navigator echo technique (2.4 +/- 0.58 vs. 3.65 +/-
      0.73 SD, p < 0.01 for all evaluation criteria). In 2/20 patients fetal movement
      severely impaired image quality in conventional and navigated HASTE. Navigator
      echo imaging revealed additional structural brain abnormalities and confirmed
      diagnosis in 8/20 patients. The accuracy improved from 50% to 90%. Average SDNR
      increased from 0.7 +/- 7.27 to 19.83 +/- 15.71 (p < 0.01). Navigator-echo-based
      real-time triggering of fetal head movement is a reliable technique that can
      deliver diagnostic fetal MR image quality despite vigorous fetal movement.

PMID- 18075743
TI  - Immunocytology in the assessment of patients with asymptomatic hematuria.
AB  - Painless hematuria has remained a diagnostic challenge in daily urological
      practice. Key problem in the assessment of these patients is the discrimination
      between malignant and non-malignant conditions. In this prospective study the
      role of immunocytology in the evaluation of patients with hematuria was
      investigated. Ucyt is a commercially available immunocytological assay based upon
      microscopical detection of tumor-associated antigens on the membrane of
      urothelial cells by immunofluorescence. Between October 2000 and July 2007, 301
      consecutive patients with a first episode of painless hematuria without prior
      transitional cell carcinoma were included. Urine samples were obtained from all
      patients and examined cytologically and immunocytologically. Clinical assessment
      by physical examination, laboratory tests, endoscopy and imaging in 228 cases
      with microhematuria and 66 cases with gross hematuria yielded bladder cancer in
      10 (4.6%) and 17 (27%) patients, respectively. Clinical workup demonstrated that
      composition of both groups was entirely different. Sensitivity of cystoscopy and
      immunocytology was similar in both groups. Furthermore, a negative finding in
      cystoscopy and immunocytology virtually excluded the presence of urothelial
      cancer. However, while predictive values of immunocytology were clearly superior
      to cytology in gross hematuria, cytology performed better in the microhematuria
      cohort. Combination of cystoscopy and immunocytology yield 100% sensitivity in
      the assessment of patients with painless hematuria. Based upon performance
      characteristics the authors recommend to replace urine cytology by a more
      sensitive marker like immunocytology in gross hematuria. In patients with
      microhematuria immunocytology could be used to select for patients at risk for
      urothelial cancer and thus spare negative patients from further examinations.

PMID- 18075745
TI  - Comparative evaluation of 5-HIAA (5-hydroxy indoleacetic acid) and HVA
      (homovanillic acid) in infantile hydrocephalus.
AB  - BACKGROUND: Infantile hydrocephalus is a common congenital problem. Functional
      and behavioral disturbances associated with hydrocephalus may be due to altered
      neurotransmitters in the brain. The role of neurotransmitters has been
      established in various psychiatric and neurological conditions. Therefore, we
      decided to study the role of 5-hydroxy indoleacetic acid (5-HIAA) and
      homovanillic acid (HVA) in cerebrospinal fluid (CSF) of hydrocephalic patients as
      diagnostic and prognostic marker. MATERIALS AND METHODS: Ventricular CSF samples
      were taken from hydrocephalic patients peroperatively and at days 7 & 30. Control
      CSF samples were taken from nonhydrocephalic patients operated for other
      conditions. Samples were analyzed for 5-HIAA and HVA, and results were obtained
      accordingly. RESULTS: Values of 5-HIAA and HVA showed a highly significant
      decrease after shunt insertion. No significant difference in values of 5-HIAA and
      HVA were observed in relation to age and duration of disease. The CSF ventriculo
      lumbar gradient for both 5-HIAA and HVA done in six patients was statistically
      significant only in the noncommunicating group. CONCLUSION: Both the
      neurotransmitter metabolites 5-HIAA and HVA are found to be significantly high in
      the hydrocephalus, but 5-HIAA is a more sensitive parameter. These markers levels
      decrease after shunt insertion. Thus, estimation of these metabolites could be
      valuable markers for its diagnosis and follow-up.

PMID- 18075744
TI  - [Lutein and antioxidants in the prevention of age-related macular degeneration].
AB  - Demographic developments in Europe and North America are causing an increase of
      age-related diseases. Age-related macular degeneration (AMD) is one of the
      leading causes of severe central visual acuity loss in elderly people and seems
      to be an economic problem, too. There is evidence that oxidative damage is an
      important factor for exacerbation of AMD. Macular pigment with its antioxidative
      effect may serve as"natural sunglasses" filtering the blue light acting as a
      possible source of photooxidative damage to the neurosensory retina. The macular
      pigment consists mostly of lutein and zeaxanthin. These micronutrients from the
      group of carotenoids, as is the case for vitamins (vitamins C, E, and beta
      carotene), cannot be synthesized in mammals and that is the reason why the role
      of micronutrition or its supplementation and its correlation to AMD progression
      has been discussed for years. The results of currently published studies are
      often contradictory. At present there are no results from randomized controlled
      studies confirming that supplementation of lutein and zeaxanthin can reduce the
      risk for AMD. Several epidemiological studies investigating the impact of
      antioxidants and omega-3 fatty acids on the incidence of AMD provided conflicting
      results.Up to now, AREDS is the largest randomized controlled study investigating
      the effect of supplementation of antioxidants, zinc, and copper on the
      progression of AMD. AREDS showed a significant effect of this supplementation in
      some particular groups of patients with AMD. The supplementation of lutein and
      omega-3 fatty acids is not toxic but a positive effect has not been proven by
      randomized studies.

PMID- 18075746
TI  - Tracing of temporo-entorhinal connections in the human brain: cognitively
      impaired argyrophilic grain disease cases show dendritic alterations but no
      axonal disconnection of temporo-entorhinal association neurons.
AB  - Argyrophilic grain disease (AGD), a neurodegenerative disorder, is often
      associated with mild to moderate Alzheimer's disease (AD)-related pathology. The
      development of dementia in AGD is associated with the extent of coexisting AD
      related pathology. Therefore, the question arises whether the degenerative
      changes in the neuronal network of demented AGD-patients represent a distinct
      pattern or show similar changes of disconnection as considered for AD. We were
      able to apply DiI-tracing in two human autopsy cases with mild AD-related
      pathology (controls), in one AD-patient, in one non-demented patient with
      advanced AD-related pathology, and in three cognitively impaired AGD-patients.
      DiI-crystals were injected into the entorhinal cortex. Pyramidal neurons of
      layers III and V of the adjacent temporal neocortex (area 35) were retrogradely
      marked with the tracer and analyzed. The AD case did not exhibit any retrogradely
      labeled neurons in the temporal neocortex. In the non-demented case with advanced
      AD-related pathology, the number of traced neurons was reduced as compared to
      that in the two controls and in the three AGD cases. In contrast, all three
      cognitively impaired AGD cases exhibited labeled pyramidal neurons in area 35 in
      an almost similar number as in the controls. However, alterations in the
      dendritic tree were observed in the AGD cases. These results show the existence
      of temporo-entorhinal connections in the adult human brain similar to those
      reported in animal models. Furthermore, the present study based on seven cases is
      the first attempt to study changes in the neuronal network in a human tauopathy
      with targeted axonal tracing techniques. Our findings in three cognitively
      impaired AGD cases suggest that AGD-related dementia constitutes a distinct
      disorder with a characteristic pattern of degeneration in the neuronal network.

PMID- 18075747
TI  - Abnormal motoneuron migration, differentiation, and axon outgrowth in spinal
      muscular atrophy.
AB  - The role of heterotopic (migratory) motoneurons (HMN) in the pathogenesis of
      spinal muscular atrophy (SMA) is still controversial. We examined the occurrence
      and amount of HMN in spinal cord tissue from eight children with SMA (six with
      SMA-I and two with SMA-II). All affected subjects were carrying a homozygous
      deletion of exon 7 in the SMN1 gene. Unlike controls, virtually free from HMN,
      all SMA subjects showed a significant number of HMN at all levels of the spinal
      cord. Heterotopic neurons were hyperchromatic, located mostly in the ventral
      white matter and had no axon or dendrites. More than half of the HMN were very
      undifferentiated, as judged from their lack of immunoreactivity for NeuN and MAP2
      proteins. Small numbers of more differentiated heterotopic neurons were also
      found in the dorsal and lateral white matter region. As confirmed by
      ultrastructural analysis, in situ end labeling (ISEL) and CD68 immunoreactivity,
      HMN in the ventral outflow were found to have no synapses, to activate microglial
      cells, and to eventually die by necrosis. An unbiased quantitative analysis
      showed a significant negative correlation between age of SMA subjects (a
      reflection of the clinical severity) and the number of HMN. Subjects who died at
      older ages had increased number of GFAP-positive astrocytes. Complementing our
      previous report on motoneuron apoptosis within the ventral horns in SMA, we now
      propose that abnormal migration, differentiation, and lack of axonal outgrowth
      may induce motoneuron apoptosis predominantly during early stages, whereas a
      slower necrosis-like cell death of displaced motoneurons which "escaped"
      apoptosis characterizes later stages of SMA.

PMID- 18075748
TI  - Tension controlled ligament balanced total knee arthroplasty: 5-year results of a
      soft tissue orientated surgical technique.
AB  - INTRODUCTION: Posterior cruciate ligament (PCL)-retaining prostheses give good
      outcomes and are commonly used. This retrospective study investigated outcomes
      from total knee arthroplasty (TKA) using the ligament balancing technique to
      implant a PCL-retaining knee prosthesis (balanSystrade mark knee system) with
      either a mobile or a fixed bearing polyethylene inlay. MATERIALS AND METHODS: A
      retrospective study was performed on patients treated with TKA at one surgical
      centre between 1997 and 2001. In this period 182 surgeries were performed.
      Clinical assessments of the implant used the Knee Society Score (KSS). Subjective
      assessments used visual analogue scale (VAS) for pain and patient satisfaction.
      The Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) was
      used to assess pain, stiffness and function of the knee. Radiographic analysis
      was performed to determine frontal and sagittal alignment and loosening. RESULTS:
      A total of 109 knee implants in 95 patients (26 men; 69 women) were followed up.
      Seventy-three cases were not available for follow-up due to bad health or death
      of the patient; 74% of 109 reviewed implants had fixed bearings and 26% had
      mobile bearings. The mean age at surgery was 72.9 +/- 7.35 years (range 54.7
      92.4). The mean KSS was 160 +/- 28.3 points. The KSS was greater for men and was
      significantly reduced when another disease was present. The type of bearing,
      surgical approach, and pre-operative alignment for patients affected by varus or
      valgus gonarthrosis had no significant impact on KSS and ROM. According to VAS
      the mean scores for pain and satisfaction were 1.48 (0 = no pain) and 9.2 (10 =
      very satisfied), respectively. The WOMAC mean scores for pain (87.0), stiffness
      (82.3) and function (78.6) were high (best outcome score of 100). There were no
      revisions due to aseptic loosening or wear. CONCLUSION: Total knee arthroplasty
      performed with a PCL-retaining prosthesis implanted by using a soft tissue
      oriented surgical technique is a safe procedure and was associated with good
      results. So far, there were few complications and no need for revision due to
      aseptic loosening. In addition, most of the patients reported little pain and
      were satisfied with the outcome. These good outcomes are comparable with other
      studies reporting on PCL-retaining prostheses.

PMID- 18075749
TI  - Persistent sciatic artery aneurysm associated with the development of
      angiosarcoma: a case report.
AB  - Persistent sciatic artery (PSA) is a very rare, but clinically significant,
      congenital anomaly. PSA is known to undergo aneurysmal formation; however, there
      have been no previous reports of a soft-tissue sarcoma arising from a PSA. We
      describe a 79-year-old woman with a 10 year history of a slowly growing mass on
      her right buttock. Physical examination revealed a painful, firm, pulsatile mass
      with a maximum diameter of 13 cm. Computed tomography angiography revealed that
      the mass arose from the PSA. We successfully excised the mass lesion with no
      postoperative circulatory disturbances. The final pathological diagnosis was
      aneurysmal PSA that focally developed secondary angiosarcoma.

PMID- 18075750
TI  - The Suv39h-HP1 histone methylation pathway is dispensable for enrichment and
      protection of cohesin at centromeres in mammalian cells.
AB  - Sister chromatids are physically connected by cohesin complexes. This sister
      chromatid cohesion is essential for the biorientation of chromosomes on the
      mitotic and meiotic spindle. In many species, cohesion between chromosome arms is
      partly dissolved in prophase of mitosis, whereas cohesion is protected at
      centromeres until the onset of anaphase. In vertebrates, the protein Sgo1,
      protein phosphatase 2A, and several other proteins are required for protection of
      centromeric cohesin in early mitosis. In fission yeast, the recruitment of
      heterochromatin protein Swi6/HP1 to centromeres by the histone-methyltransferase
      Clr4/Suv39h is required for enrichment of cohesin at centromeres already in
      interphase. We have tested if the Suv39h-HP1 histone methylation pathway is also
      required for enrichment and mitotic protection of cohesin at centromeres in
      mammalian cells. We show that cohesin and HP1 proteins partially colocalize at
      mitotic centromeres but that cohesin localization is not detectably altered in
      mouse embryonic fibroblasts that lack Suv39h genes and in which HP1 proteins can,
      therefore, not be properly enriched in pericentric heterochromatin. Our data
      indicate that the Suv39h-HP1 pathway is not essential for enrichment and mitotic
      protection of cohesin at centromeres in mammalian cells.

PMID- 18075751
TI  - Bone marrow-derived progenitor cells promote corneal wound healing following
      alkali injury.
AB  - PURPOSE: To determine whether bone marrow-derived progenitor cells can be
      stimulated by inflammatory mediators and play a role in corneal wound healing
      following alkali injury. METHODS: Sixty rabbits were divided into two groups
      (Group I and Group II). Group I served as a bone marrow-suppression model, and
      received 200 mg/kg cyclophosphamide. Corneal alkali injury was created in one eye
      of each rabbit in each group; the other eye served as control. Three days after
      corneal burn, inflammatory cells in peripheral blood were counted. At the end of
      4 weeks follow-up, corneas of all rabbits were subjected to histochemical
      examination to assess infiltrated CD34 and C-kit positive cells. Clinical outcome
      was determined at the end of 4 weeks. RESULTS: Cyclophosphamide suppressed bone
      marrow function in Group I by reducing cellularity by more than 30% and
      neutrophil distribution by 3.18 +/- 1.83%. The number of bone marrow
      hematopoietic and mesenchymal progenitor cells were all suppressed by
      cyclophophamide, as demonstrated by statistically significant differences between
      Group I and Group II of CD34+ cells (t = -21.62, P < 0.01) and C-Kit cells (t = 
      21.62, P < 0.01). Fewer inflammatory cells were released into circulation in
      Group I (14.42 +/- 5.70%) than in Group II (44.36 +/- 8.64%). Clinical
      observation revealed that Group II rabbits had much greater reepithelization (t =
      6.999, P < 0.01) and clearer corneas (X(2) = 4.417, P < 0.01) than Group I.
      CONCLUSIONS: Corneal alkali injury is a stimulus that induces a rapid bone marrow
      reaction to release not only inflammatory cells but also progenitor cells into
      circulation. Migrated bone marrow-derived progenitor cells can home to local
      sites to promote wound healing.

PMID- 18075754
TI  - Ergonomic comparison of a chem/bio prototype firefighter ensemble and a standard
      ensemble.
AB  - Firefighter turnout gear and equipment protect the wearer against external
      hazards but, unfortunately, restrict mobility. The aim of this study was to
      determine the ease of mobility and comfort while wearing a new prototype
      firefighter ensemble (PE) with additional chemical/biological hazard protection
      compared to a standard ensemble (SE) by measuring static and dynamic range of
      motion (ROM), job-related tasks, and comfort. Eight healthy adults (five males,
      three females), aged 20-40 years, participated in this study. The study consisted
      of two repeated phases, separated by five uses of the ensembles. Subjects
      randomly donned either the SE or PE in either dry or wet conditions on separate
      days. In each phase, five tests were carried out as follows: baseline (non
      ensemble), SE-dry, SE-wet, PE-dry, and PE-wet. There was a significant reduction
      (P < 0.05) of wrist flexion for PE-dry condition compared to the same SE-dry
      condition. Donning the PE took 80 s longer than the SE in phase 1, this
      difference disappeared in phase 2. There was a significant decrease (P < 0.05) in
      post-test comfort wearing the PE compared to the SE. The data collected in this
      study suggest that, in spite of design features to enhance chemical/biological
      hazard protection, the PE design does not decrease the wearer's overall
      functional mobility compared to the SE. However, subjects seem to be more
      comfortable wearing the SE compared to the PE. These overall findings support the
      need for a comprehensive ergonomic evaluation of protective clothing systems to
      ascertain human factors issues.

PMID- 18075755
TI  - Behavior of submicrometer particles in periodic alveolar airflows.
AB  - Here, we report a numerical experiment in which submicrometer particle
      entrainment in a periodic flow that matches those existing in the alveolus in the
      human lung was simulated for both sedentary and light activity. A spherical
      cavity with a prescribed velocity profile at the inlet was used to simulate the
      time-dependent periodical flow of air in the alveolus. Expansion and contraction
      of the alveolus were simulated by setting a conceptual permeable wall as the
      outer surface of the model and adjusting the boundary conditions in order to
      match the continuity of the flow. The simulations were conducted for breathing
      periods of 5 and 3 s, which match sedentary and light activity conditions,
      respectively, and the results were extrapolated to the real lung. It was found
      that, most of the particles mainly followed a straightforward path and reached
      the opposite side of the alveolar wall in both breathing conditions. The
      concentration patterns obtained are consistent with the fact that the flow within
      the alveolus is mainly diffusive and does not greatly depend on the flow
      velocity. It was found that the particles which are heavier than air move out of
      phase with the periodic airflow that crosses the alveolus entrance, and that
      these particles are significantly caught within the alveolus. Particle entrapment
      increases with breathing rate in accordance with experimental values and
      indicates that increase in breathing frequency in environments with high
      concentration of submicrometer particles has the consequence of increasing
      particle entrapment by several times with respect to normal breathing rate.

PMID- 18075753
TI  - Protein quality control: the who's who, the where's and therapeutic escapes.
AB  - In cells the quality of newly synthesized proteins is monitored in regard to
      proper folding and correct assembly in the early secretory pathway, the cytosol
      and the nucleoplasm. Proteins recognized as non-native in the ER will be removed
      and degraded by a process termed ERAD. ERAD of aberrant proteins is accompanied
      by various changes of cellular organelles and results in protein folding
      diseases. This review focuses on how the immunocytochemical labeling and electron
      microscopic analyses have helped to disclose the in situ subcellular distribution
      pattern of some of the key machinery proteins of the cellular protein quality
      control, the organelle changes due to the presence of misfolded proteins, and the
      efficiency of synthetic chaperones to rescue disease-causing trafficking defects
      of aberrant proteins.

PMID- 18075756
TI  - Artificial synaptic modification reveals a dynamical invariant in the pyloric
      CPG.
AB  - The sequential firing of neurons in central pattern generators (CPGs) is
      generally thought to be a result of an interaction between intrinsic cellular and
      synaptic properties of the component neurons. Due to experimental limitations, it
      is usually difficult to address the role of each of these properties separately.
      We have done so by using the crustacean stomatogastric CPG and the dynamic clamp
      technique to measure how the network responds to the selective modification of an
      individual important synapse. Our results show that the burst periods and the
      phase lags between the constrictor (LP) and dilator (PD) neurons across
      preparations showed significant variability during equivalent experimental
      manipulations. Despite this variability, the ratio between the change in the
      burst period and the change in the phase lag between the same neurons was tightly
      preserved in all preparations, revealing a dynamical invariant in the system.
      This dynamical invariant was preserved despite the individual variability in the
      period and phase lag measurements, suggesting a tightly regulated constraint
      between the parameters of the network.

PMID- 18075757
TI  - The interaction domains of the plant Myc-like bHLH transcription factors can
      regulate the transactivation strength.
AB  - The N-terminal region of the plant Myc-like basic helix-loop-helix transcription
      factors (bHLH TFs) contains two domains. Approximately, 190 amino acids at the N
      terminus comprise an interaction domain, a.k.a. Myb-interacting-region (MIR) for
      its primary function of interacting with Myb-like TFs. Following, the interaction
      domain is an activation (or acidic) domain responsible for transactivation. We
      have previously discovered that a lysine to methionine substitution (K157M) in
      the interaction domain of Myc-RP of Perilla frutescens leads to a 50-fold
      increase in transactivation activity. The result suggests that mutations in the
      interaction domain affect transactivation. The highly conserved nature of this
      lysine residue in many Myc-like bHLH TFs prompted us to explore the functional
      importance of this residue within the TF family and the influence of the
      interaction domain on the activation domain in transactivation. We found that the
      replacement of the equivalent lysine with methionine significantly affects the
      transactivation activities of two other Myc-RP homologues, Delila from snapdragon
      and Lc from maize. In addition to methionine, substitution with several other
      amino acids at this position has positive effects on transcriptional activity. A
      neighboring conserved alanine residue (A159 in Myc-RP, A161 in Delila and A172 in
      Lc) also affects transactivation. Substitution of this alanine residue to an
      aspartic acid abolished transactivation of both Myc-RP and Delila and severely
      reduced transactivation of Lc. Ectopic expression of a Myc-RP K157M mutant in
      transgenic tobacco resulted in increased anthocyanin accumulation compared to
      plants expressing the wild-type gene. Our study reveals the potential cooperation
      between functional domains of the bHLH TFs.

PMID- 18075758
TI  - Histopathological assessment of anastrozole and tamoxifen as preoperative
      (neoadjuvant) treatment in postmenopausal Japanese women with hormone receptor
      positive breast cancer in the PROACT trial.
AB  - PURPOSE: The PReOperative 'Arimidex' Compared with Tamoxifen (PROACT) trial
      compared neoadjuvant anastrozole and tamoxifen in postmenopausal women with
      large, operable or potentially operable, locally advanced hormone receptor
      positive breast cancer. Here, we compare objective clinical responses with
      histopathological tumor responses to therapy in a cohort of 97 Japanese patients,
      in order to investigate the consistency of assessment methods and the change in
      estrogen-receptor (ER) and progesterone-receptor (PgR) status. METHODS:
      Histopathological response and the change in ER and PgR status were assessed by
      comparing pathological specimens collected at baseline (via needle biopsy) with
      those collected at 3 months (from excised tumors). The response was evaluated
      using Pathological Response Criteria for Breast Cancer as defined by the Japanese
      Breast Cancer Society. The patients were randomized to receive anastrozole (n =
      48) or tamoxifen (n = 49). RESULTS: A numerically greater histopathological
      response rate was observed when neoadjuvant anastrozole compared with neoadjuvant
      tamoxifen (35.4 and 12.2%, respectively). The histopathological and clinical
      objective response rates agreed in 63/97 patients. The ER status of 5/40 patients
      changed from positive at baseline to negative at 3 months in the anastrozole
      group compared with 20/37 patients in the tamoxifen group. The PgR status of
      16/17 patients in the anastrozole group and of 1/11 patients in the tamoxifen
      group changed from positive to negative. CONCLUSIONS: These data support the
      findings of the main PROACT trial, which confirmed that anastrozole, as compared
      with tamoxifen, is an effective neoadjuvant endocrine treatment in objective
      response rates for postmenopausal women with large operable hormone-receptor
      positive breast cancer. Further follow-up is required to confirm whether
      histopathological responses to therapy correlate with an overall improvement in
      survival.

PMID- 18075759
TI  - Do natural container habitats impede invader dominance? Predator-mediated
      coexistence of invasive and native container-dwelling mosquitoes.
AB  - Predator-mediated coexistence of competitors occurs when a species that is
      superior in competition is also more vulnerable to a shared predator compared to
      a poorer competitor. The invasive mosquito Aedes albopictus is usually
      competitively superior to Ochlerotatus triseriatus. Among second instar larvae,
      A. albopictus show a lesser degree of behavioral modification in response to
      water-borne cues from predation by the larval midge Corethrella appendiculata
      than do O. triseriatus, rendering A. albopictus more vulnerable to predation by
      C. appendiculata than O. triseriatus. The hypothesis that C. appendiculata
      predation favors coexistence of these competitors predicts that C. appendiculata
      abundances will be negatively and positively correlated with A. albopictus and O.
      triseriatus abundances, respectively, and that coexistence will occur where C.
      appendiculata are common. Actual abundances of O. triseriatus, A. albopictus, and
      C. appendiculata in three habitats fit this prediction. In natural container
      habitats like tree holes, C. appendiculata were abundant and competitors co
      existed at similar densities. In cemeteries and tires, which occur primarily in
      non-forested, human-dominated habitats, A. albopictus dominated, with abundances
      twice those found in tree holes, but C. appendiculata and O. triseriatus were
      rare or absent. We also tested for whether antipredatory behavioral responses of
      A. albopictus differed among habitats or populations, or were correlated with
      local C. appendiculata abundances. We could detect no differences in A.
      albopictus antipredatory behavioral responses to water-borne cues from predation.
      Tree hole habitats appear to promote co-existence of O. triseriatus and A.
      albopictus through interactions with predatory C. appendiculata, and this
      predator effect appears to limit invasion success of A. albopictus in tree holes.
      There are many studies on predator-mediated coexistence in natural habitats but
      to our knowledge this is the first study to suggest differential predator
      mediated coexistence between natural and man-made habitats.

PMID- 18075760
TI  - Effectiveness of rodents as local seed dispersers of Holm oaks.
AB  - In this study we assessed the effectiveness of rodents as dispersers of Quercus
      ilex in a patchy landscape in southeastern Spain. We experimentally followed the
      fates of 3,200 marked and weighed acorns from dispersal through the time of
      seedling emergence over three years. Rodents handled about 99% of acorns, and
      dispersed 67% and cached 7.4% of the dispersed acorns. Most caches were recovered
      and consumed, and only 1.3% of the original experimental acorns were found alive
      in caches the following spring. Dispersal distances were short (mean = 356.2 cm,
      median = 157 cm) and strongly right-skewed. Heavier acorns were dispersed further
      and were more likely to be cached and survive than lighter acorns. All caches
      were in litter or soil, and each contained a single acorn. Rodents moved acorns
      nonrandomly, mostly to oaks and pines. Most surviving acorns were either in oaks,
      a poor microhabitat for oak recruitment, or shrubs, a suitable microhabitat for
      oak recruitment. Our results suggest that rodents, by burying a relatively high
      proportion of acorns singly in shrubs and pines, act as moderately effective
      dispersers of Q. ilex. Nonetheless, this dispersal comes at a very heavy cost.

PMID- 18075761
TI  - [Implementation of a standardized perioperative pain management concept in three
      hospitals of a consortium].
AB  - BACKGROUND: Provision of sufficient perioperative pain therapy is an obligation
      in the clinical management of patients suffering from pain. The implementation of
      a standardized pain management concept was planned to be introduced in the
      clinical routine. The results of three hospitals are shown. MATERIAL AND METHODS:
      The concept included tools which gave information about legal aspects and basic
      fundamentals of pain relief, management modules regarding agreements on the
      implementation of perioperative pain therapy, instruments to measure pain
      intensity, assigning accountability and documentation modules. Questionnaires
      were carried out according to Picker. RESULTS: The project revealed that,
      according to the Picker questionnaire, about 50% of the patients treated in the
      hospitals had pain, 30-40% still had intensive pain during the stay in hospital
      and 90% of the patients received pain relief medication within 10 min of the
      request. More than 78% of the patients thought the hospital staff did their best
      to relieve the pain and over 92% found the pain treatment adequate. CONCLUSION:
      It was possible to implement a standardized perioperative pain therapy concept in
      three hospitals of a consortium. Whether an adequate pain relief can be improved
      with the help of standard measurements and documentation, could not be evaluated
      in this study.

PMID- 18075762
TI  - Radiculopathy due to malignant melanoma in the sacrum with unknown primary site.
AB  - Melanoma is an interesting tumor, showing the appearance of metastasis without
      any trace of its primary lesion. To report a very rare case of malignant melanoma
      in the sacrum with unknown primary origin. The authors present a case of a 52
      year-old man who was admitted with increasing lower back, left buttock, and left
      lower extremity pain, and dysuria. Plain radiograph, computed tomography scan,
      and magnetic resonance imaging revealed a destructive lesion in the sacrum and
      left ilium, which infiltrated the spinal canal and sacroiliac joint. The tumor
      cells were immunoreactive for HMB-45. The pathological diagnosis was malignant
      melanoma. No obvious primary malignant melanoma was detected on the skin surface,
      on the oral or anal mucosa, or in the fundus oculi. Following radiotherapy and
      chemotherapy, the severe buttock pain disappeared and the patient was able to
      walk without impediment. However the patient died nine months after initial
      diagnosis. Malignant melanoma in the sacrum with an unknown primary site, showing
      S1 radiculopathy is reported for the first time. The melanoma could have been a
      metastatic tumor of the sacrum, although the primary site was not detected. The
      incidence of primary melanoma is increasing faster than any other cancer. Thus
      treatment of patients with spinal metastasis of melanoma is an important
      challenge for orthopedic surgeons.

PMID- 18075763
TI  - The diagnosis and management of infection following instrumented spinal fusion.
AB  - A 10-year retrospective audit. (1) The incidence of infection; (2) causative
      organisms; (3) whether eradication of infection is achievable with spinal implant
      retention; (4) patient outcome. The reported incidence of infection following
      posterior spinal instrumentation is between 2.6 and 3.8%. Management of infection
      is controversial, with some advocating serial wound debridement while others
      report that infection cannot be eradicated with retention of implants. There are
      no published data demonstrating that propionibacteria are associated with early
      postoperative infection. The management of infected cases at our institution
      includes eventual removal of their implants. Our population was identified by
      studying the case notes of all patients who had undergone removal of spinal
      implants and cross-referencing this population with positive microbiology or
      histology reports. The incidence of infection was 3.7%. Propionibacteria were
      isolated in 45% of cases. The diagnosis of infection was unexpected in 25% of
      patients, following removal of implants for prominence of implants or back pain.
      Sixty per cent of patients with acute postoperative deep wound infection had
      continuing active infection on subsequent removal of implants, despite long-term
      antibiotics and wound debridement. Fourty-six per cent of patients had a stable,
      pain-free spine at the end of their treatment. This is the largest reported
      series of infections following posterior spinal instrumented fusions of which we
      are aware. Propionibacteria are a common cause of infection and successful
      eradication of infection cannot be reliably achieved with antibiotics and wound
      debridement alone.

PMID- 18075764
TI  - Stress biomarkers' associations to pain in the neck, shoulder and back in healthy
      media workers: 12-month prospective follow-up.
AB  - Physiological and psychological mechanisms have been proposed to link stress and
      musculoskeletal pain (MSP), and a number of stress biomarkers in patients with
      chronic pain have shown to be associated with stress-related disorders as well as
      health and recovery. The aim was to study if similar results might be found in a
      working population, in stress and computer intensive occupations with
      mild/moderate pain in neck, shoulder and back. The questions were if there are:
      (1) associations between self rated neck, shoulder and back pain (VAS) on one
      hand and stress-related (catabolic), recovery related (anabolic) variables,
      cardiovascular/lifestyle factors and immune markers on the other hand. (2)
      associations between long term changes in pain and stress marker values (6 month
      period). (3) predictive values in stress biomarkers for pain (12 month period) A
      study group with 121 media workers, 67 males (average 45 years) and 53 females
      (average 43 years), at three news departments of a media company was recruited.
      Pain occurrence and pain level in neck, shoulder, upper and low back were self
      rated at three times with a 6-month interval towards the last month. Stress
      biomarker sampling was performed, at the same intervals. An additional similar
      questionnaire with momentary ratings focusing on "at present" i.e. within the
      same hour as stress biomarker sampling was performed. There were no changes in
      medicine intake or computer working hours during the 12 month study period. The
      total pain level and prevalence of pain decreased between baseline and 12 months
      follow-up. The rate of participation was 95%. Cross-sectional analyses on
      differences in stress biomarkers in groups of "no pain" and "pain" showed less
      beneficial stress biomarker levels (P < 0.05) in the "pain" group after age and
      gender adjustments in: S-DHEA-S and P-endothelin, S-insulin and P-fibrinogen.
      Analyses of each gender separately, adjusted for age, revealed in males
      differences in S-insulin, saliva cortisol 3, and P-endothelin. Furthermore,
      tendencies were seen in BMI, P-fibrinogen, and S-testosterone. In the female
      "pain" group a less beneficial P-BNP level was found. Longitudinal analysis of
      changes in pain levels and stress biomarkers within an interval of 6 months
      showed beneficial changes in the following stress markers: P-NPY, S-albumin, S
      growth hormone and S-HDL when pain decreased, and vice versa when pain increased.
      Linear regression analyses showed statistically significant predicting values at
      the initial test instance for pain 12 months later in lower S-DHEA-S and S
      albumin and higher B-HbA1c and P-fibrinogen. In stepwise regression and after age
      and gender adjustments, the associations with S-DHEA-S remained statistically
      significant. The present study shows that individuals in working life with a high
      level of regenerative/anabolic activity have less pain than other subjects, and
      that decreased regenerative/anabolic activity is associated with increasing pain.
      The levels of NPY, albumin, GH and HDL increased when pain decreased and vice
      versa. Low DHEA-S predicted pain 12 months later. These findings might contribute
      to increased knowledge about strategies to prevent further progression of
      neck/shoulder/back pain in persons who are "not yet in chronic pain".

PMID- 18075765
TI  - Molecular electronegativity distance vector model for the prediction of
      bioconcentration factors in fish.
AB  - Molecular electronegativity distance vector (MEDV) derived directly from the
      molecular topological structures was used to describe the structures of 122
      nonionic organic compounds (NOCs) and a quantitative relationship between the
      MEDV descriptors and the bioconcentration factors (BCF) of NOCs in fish was
      developed using the variable selection and modeling based on prediction (VSMP).
      It was found that some main structural factors influencing the BCFs of NOCs are
      the substructures expressed by four atomic types of nos. 2, 3, 5, and 13, i.e.,
      atom groups -CH(2)- or =CH-, -CH< or =C<, -NH(2), and -Cl or -Br where the former
      two groups exist in the molecular skeleton of NOC and the latter three groups are
      related closely to the substituting groups on a benzene ring. The best 5-variable
      model, with the correlation coefficient (r(2)) of 0.9500 and the leave-one-out
      cross-validation correlation coefficient (q(2)) of 0.9428, was built by multiple
      linear regressions, which shows a good estimation ability and stability. A
      predictive power for the external samples was tested by the model from the
      training set of 80 NOCs and the predictive correlation coefficient (u(2)) for the
      42 external samples in the test set was 0.9028.

PMID- 18075766
TI  - Clinical trial updates and hotline sessions presented at the Scientific Session
      2007 of the American Heart Association.
AB  - This article provides information and commentaries on trials which were presented
      at Clinical Trial Updates and Hotline Sessions presented at the Scientific
      Sessions 2007 of the American Heart Association in Orlando, Florida. The
      comprehensive summaries have been generated from the oral presentations and the
      webcasts of the American Heart Association. Most reports have not been published
      as full papers and therefore have to be considered as preliminary data, as the
      analysis may change in the final publications. The following papers are
      discussed: TRITON TIMI-38, EVA-AMI, BRIEF-PCI, RACE, MASS Stent, HF-ART, STITCH,
      CORONA, ILLUMINATE, CORE-64, OAT Substudy, AFCHF, MASCOT, RETHINQ, MASTER I,
      POISE, COUMA-GEN, HIJ-CREATE, PROVIDENCE I, CAUSMIC, IC-BMC, IC/IM BMCs.

PMID- 18075767
TI  - Ventricular tachycardia and aggravation of Brugada ECG pattern in a patient with
      coronary artery disease and combined amiodarone and betablocker therapy.

PMID- 18075768
TI  - Conflict between a patient's family and the medical team.

PMID- 18075769
TI  - Genetic diagnosis, confidentiality and counseling: an ethics committee's
      potential deliberations about the do's and don'ts.

PMID- 18075770
TI  - Case report: parental request for life-prolonging interventions.

PMID- 18075771
TI  - The complex roles of relatives in end-of-life decision-making: an ethical
      analysis.

PMID- 18075772
TI  - Current problems of clinical ethics: confidentiality and end-of-life decisions-
      is silence always golden?

PMID- 18075773
TI  - The duty to warn and clinical ethics: legal and ethical aspects of
      confidentiality and HIV/AIDS.

PMID- 18075774
TI  - Confidentiality, secrecy and privacy in ethics consultation.

PMID- 18075775
TI  - The role of family in euthanasia decision making.

PMID- 18075776
TI  - Universal risk factors for multifactorial diseases: LifeLines: a three-generation
      population-based study.
AB  - The risk for multifactorial diseases is determined by risk factors that
      frequently apply across disorders (universal risk factors). To investigate
      unresolved issues on etiology of and individual's susceptibility to
      multifactorial diseases, research focus should shift from single determinant
      outcome relations to effect modification of universal risk factors. We present a
      model to investigate universal risk factors of multifactorial diseases, based on
      a single risk factor, a single outcome measure, and several effect modifiers.
      Outcome measures can be disease overriding, such as clustering of disease,
      frailty and quality of life. "Life course epidemiology" can be considered as a
      specific application of the proposed model, since risk factors and effect
      modifiers of multifactorial diseases typically have a chronic aspect. Risk
      factors are categorized into genetic, environmental, or complex factors, the
      latter resulting from interactions between (multiple) genetic and environmental
      factors (an example of a complex factor is overweight). The proposed research
      model of multifactorial diseases assumes that determinant-outcome relations
      differ between individuals because of modifiers, which can be divided into three
      categories. First, risk-factor modifiers that determine the effect of the
      determinant (such as factors that modify gene-expression in case of a genetic
      determinant). Second, outcome modifiers that determine the expression of the
      studied outcome (such as medication use). Third, generic modifiers that determine
      the susceptibility for multifactorial diseases (such as age). A study to assess
      disease risk during life requires phenotype and outcome measurements in multiple
      generations with a long-term follow up. Multiple generations will also enable to
      separate genetic and environmental factors. Traditionally, representative
      individuals (probands) and their first-degree relatives have been included in
      this type of research. We put forward that a three-generation design is the
      optimal approach to investigate multifactorial diseases. This design has
      statistical advantages (precision, multiple-informants, separation of non-genetic
      and genetic familial transmission, direct haplotype assessment, quantify genetic
      effects), enables unique possibilities to study social characteristics
      (socioeconomic mobility, partner preferences, between-generation similarities),
      and offers practical benefits (efficiency, lower non-response). LifeLines is a
      study based on these concepts. It will be carried out in a representative sample
      of 165,000 participants from the northern provinces of the Netherlands. LifeLines
      will contribute to the understanding of how universal risk factors are modified
      to influence the individual susceptibility to multifactorial diseases, not only
      at one stage of life but cumulatively over time: the lifeline.

PMID- 18075777
TI  - An interspecific hybrid as a tool to study phylogenetic relationships in plants
      using the GISH technique.
AB  - We established a new auxiliary phylogenetic approach based on genomic in situ
      hybridization technique (GISH). We used an interspecific hybrid Silene latifolia
      x Silene viscosa to compare two different genomes simultaneously on one slide. By
      using GISH with genomic DNA from another closely related species as a probe, we
      directly compared the level of relatedness between the genomes of the studied
      species and parental species. This experimental design enabled us to
      approximately estimate evolutionary relationships between the genome of tested
      plant species and genomes of both parental species of the hybrid by using the
      ratio of intensities of fluorescence signals. We tested this technique in various
      Silene species and the results were in accordance with the topology of the
      phylogenetic tree we constructed based on rDNA sequences. The results were also
      well correlated with phylogenetic distances between species that we estimated
      from an rDNA-based phylogenetic tree. Our experimental approach could help to
      improve tree topology and serve as a useful complementary tool in molecular
      phylogenetic studies in related species.

PMID- 18075779
TI  - Contamination of nitrate and fluoride in ground water along the Ganges Alluvial
      Plain of Kanpur district, Uttar Pradesh, India.
AB  - Nitrate-N and Fluoride concentrations were analyzed in shallow and unconfined
      ground water aquifers of Kanpur district along the Ganges Alluvial Plain of
      Northern India. Kanpur district was divided into three zones namely, Bithore,
      Kanpur City and Beyond Jajmau and sampling was carried out three seasons (summer,
      monsoon and winter). The data set consisted of the results of water samples from
      around 99 India Mark II hand Pumps, which were analyzed for summer monsoon and
      winter seasons. In Bithore zone, 19% of the samples exceeded the BIS (Bureau of
      India Standards) limit 10.2 mg/l as nitrate-N and as high as 166 mg/l as nitrate
      N was observed. 10% and 7% samples in Kanpur city and beyond Jajmau zone
      respectively, exceeded the BIS limit. The Frequency distribution histogram of
      nitrate-N revealed a skewed (non-normal) distribution. Both point and non-point
      sources contribute to the ground water contamination. Especially in Bithore zone,
      the point sources could be attributed to the animal wastes derived from cows and
      buffaloes and non point sources could be due to the extensive agricultural
      activity prevalent in that area. Fluoride concentration in most samples was
      within the BIS maximum permissible level of 1.5 mg/l. No significant seasonal
      variation in water quality parameters was observed.

PMID- 18075778
TI  - Localization of telomeres and telomere-associated proteins in telomerase-negative
      Saccharomyces cerevisiae.
AB  - Cells lacking telomerase cannot maintain their telomeres and undergo a telomere
      erosion phase leading to senescence and crisis in which most cells become
      nonviable. On rare occasions survivors emerge from these cultures that maintain
      their telomeres in alternative ways. The movement of five marked telomeres in
      Saccharomyces cerevisiae was followed in wild-type cells and through erosion,
      senescence/crisis and eventual survival in telomerase-negative (est2::HYG) yeast
      cells. It was found that during erosion, movements of telomeres in est2::HYG
      cells were indistinguishable from wild-type telomere movements. At
      senescence/crisis, however, most cells were in G(2) arrest and the nucleus and
      telomeres traversed back and forth across the bud neck, presumably until cell
      death. Type I survivors, using subtelomeric Y' amplification for telomere
      maintenance, continued to show this aberrant telomere movement. However, Type II
      survivors, maintaining telomeres by a sudden elongation of the telomere repeats,
      became indistinguishable from wild-type cells, consistent with growth properties
      of the two types of survivors. When telomere-associated proteins Sir2p, Sir3p and
      Rap1p were tagged, the same general trend was seen-Type I survivors retained the
      senescence/crisis state of protein localization, while Type II survivors were
      restored to wild type.

PMID- 18075780
TI  - Evaluation of the water quality related to the acid mine drainage of an abandoned
      mercury mine (Alasehir, Turkey).
AB  - Mobility of metals in water, mine wastes, and stream sediments around the
      abandoned Alasehir mercury mine was investigated to evaluate the environmental
      effects around the area. Mine waters are dominantly acidic with pH values of 2.55
      in arid season and 2.70 in wet season and are sulfate rich. Acidity is caused
      mainly by the oxidation of sulfide minerals. Pyrite is the main acid-producing
      mineral in the Alasehir area. Of the major ions, SO(4) shows a notable increase
      reaching 3981 mg/l, which exceeds the WHO (WHO guidelines for drinking water
      quality, vol. 2. Health criteria and other supporting information, 1993) and TS
      (Sular-Icme ve kullanma sulari. Ankara: Turk Standartlari Enstitusu, 1997)
      drinking water standard of 250 mg/L. Mine waters have As, Fe, Mn, Ni, and Al with
      concentrations higher than drinking water standards. Hg concentrations of adit
      water samples and surface waters draining the mine area are between 0.25 and
      0.274 microg/L and are below the WHO (WHO guidelines for drinking water quality,
      vol. 2. Health criteria and other supporting information, 1993) drinking water
      standard of 1.0 microg/L. However, the concentrations are above the 0.012
      microg/L standard (EPA, Water quality standards. Establishment of numeric
      criteria for priority toxic pollutants, states' compliance, final rule. Fed.
      Reg., 40 CFR, Part 131, 57/246, 60847-60916, 1992) used to protect aquatic life.
      Stream sediment samples have abnormally high values of especially Hg, As, Ni, and
      Cr metals. Geoaccumulation (Igeo) and pollution index (PI) values are
      significantly high and denote heavy contamination in stream sediments. The stream
      sediments derived from the mining area with the surface waters are potentially
      hazardous to the environment adjacent to the abandoned Hg mine and are in need of
      remediation.

PMID- 18075781
TI  - Do microdeletions in the AZF region of the Y chromosome accompany cryptorchidism
      in Turkish children?
AB  - OBJECTIVE: To investigate the presence of Y chromosome microdeletions in children
      with cryptorchidism. MATERIALS AND METHODS: Male patients aged between 1 and 17
      years, who had been diagnosed by physical examination to have cryptorchid testes,
      were included in the study. Microdeletions of 24 gene loci belonging to the AZF
      a, AZF-b and AZF-c regions of the Y chromosome were examined by multiplex
      polymerase chain reaction (PCR) multiplication of the DNA sample extracted from
      peripheral leukocytes. RESULTS: Sixty-four patients with a mean age of 7.82+/
      3.21 (range: 1-17) years were included in the study. There was unilateral
      cryptorchidism in 53.1% (34/64) of the patients and bilateral cryptorchidism in
      46.8% (30/48) of the patients. No microdeletion of gene loci on the AZF-a, AZF-b
      and AZF-c regions of the Y chromosome was determined in any patient. CONCLUSION:
      Studies on Y chromosome microdeletions are important due to a potential for the
      transmission of genetic abnormalities to offspring. Assisted reproduction
      techniques may cause the transmission of genetic abnormalities to offspring
      because the physiological fertilisation mechanism is bypassed. It was found that
      there was probably no aetiologic correlation between microdeletions in gene loci
      on the AZF-a, AZF-b and AZF-c regions of the Y chromosome and cryptorchidism.

PMID- 18075782
TI  - Pigmentation in Black-boned sheep (Ovis aries): association with polymorphism of
      the MC1R gene.
AB  - Variations in vertebrate skin and hair color are due to varied amounts of
      eumelanin (brown/black) and phaeomelanin (red/yellow) produced by the
      melanocytes. The melanocortin 1 receptor (MC1R) is a regulator of eumelanin and
      phaeomelanin production in the melanocytes, and MC1R mutations causing coat color
      changes are known in many vertebrates. We have sequenced the entire coding region
      of the MC1R gene in Black-boned, Nanping indigenous and Romney Marsh sheep
      populations and found two silent mutation sites of A12G and G144C, respectively.
      PCR-RFLP of G144C showed that frequency of allele G in Black-boned, Nanping
      indigenous and Romney Marsh sheep was 0.818, 0.894 and 0, respectively. Sheep
      with GG genotype had significantly higher (P < 0.05) tyrosinase activity than
      sheep with CC genotype in the all investigated samples. Moreover, there was
      significant effect of MC1R genotype on coat color, suggesting that MC1R gene
      could affect coat color but not black traits. There would be merit in further
      studies using molecular techniques to elucidate the cause of black traits in
      these Black-boned sheep.

PMID- 18075783
TI  - Towards the applied: the construction of ethical positions in stem cell
      translational research.
AB  - This paper aims to make an empirically informed analytical contribution to the
      development of a more socially embedded bioethics. Drawing upon 10 interviews
      with cutting edge stem cell researchers (5 scientists and 5 clinicians) it
      explores and illustrates the ways in which the role positions of translational
      researchers are shaped by the [Symbol: see text]normative structures' of science
      and medicine respectively and in combination. The empirical data is used to
      illuminate three overlapping themes of ethical relevance: what matters in stem
      cell research, experimental treatment, and responsible claim making (as
      contrasted with [Symbol: see text]hype'). Finally, we suggest that this kind of
      [Symbol: see text]descriptive' ethical analysis has potential relevance for
      understanding other substantive areas of stem cell ethics in practice, and we
      briefly consider the questions our analysis raises about role positions and
      ethical agency, and the implications for bioethics as a field of scholarship.

PMID- 18075784
TI  - Tooth loss, chewing ability and quality of life.
AB  - OBJECTIVES: Middle-aged and older adults are retaining teeth and avoiding
      dentures, which should impact quality of life. The aims of our study were to
      investigate tooth loss and chewing ability and their association with oral- and
      general-health-related quality of life and life satisfaction. METHODS: A random
      sample of 45- to 54-year-olds from Adelaide, South Australia, was surveyed by
      self-complete questionnaire in 2004-2005 (n = 879, response rate = 43.8%). Health
      related quality of life was measured with the Oral Health Impact Profile 14-item
      version and EuroQol Visual Analogue Scale instruments and life satisfaction by
      the Satisfaction with Life Scale. Functional tooth units were recorded at oral
      examinations performed by calibrated dentists on 709 persons (completion rate =
      80.7%). RESULTS: Number of functional teeth was positively associated with
      chewing ability (beta = 0.31, P < 0.01). In multivariate analyses, controlling
      for number of functional teeth and other explanatory variables spanning dental
      visit pattern, dental behaviour, socio-demographics and socio-economic status,
      chewing ability was negatively associated with oral-health-related impacts (beta
      = -0.37, P < 0.01) and positively associated with general health (beta = 0.10, P
      < 0.05) and well-being (beta = 0.16, P < 0.01). CONCLUSIONS: Chewing ability was
      related to oral-health-related quality of life and general health, possibly
      reflecting the impact of chewing on food choice and enjoyment of meals and diet,
      and also indicated the importance of oral health to general well-being.

PMID- 18075785
TI  - Circulating transforming growth factor-beta-1 and breast cancer prognosis:
      results from the Shanghai Breast Cancer Study.
AB  - INTRODUCTION: Studies investigating the prognostic effect of circulating TGF-beta
      1 in breast cancer have given inconsistent findings. The purpose of this study is
      to evaluate whether circulating transforming growth factor beta 1 (TGF-beta-1) is
      associated with overall and disease-free survival in a cohort of recently
      diagnosed breast cancer patients. METHODS: We measured TGF-beta-1 levels in
      plasma samples of breast cancer patients in the Shanghai Breast Cancer Study, a
      population-based case-control study. We evaluated the relationship between TGF
      beta-1 levels and overall and disease-free survival. The median follow up time
      was 7.2 years. RESULTS: We observed that, compared with the patients with the
      lowest quartile of plasma TGF-beta-1, patients with the highest quartile of
      plasma TGF-beta-1 had significantly worse overall survival with hazards ratio
      (HR) = 2.78, with 95% confidence interval (CI): 1.34-5.79 and disease-free
      survival with HR = 2.49, 95% CI: 1.15-5.41, while the patients with the second
      and third quartiles of plasma TGF-beta-1 did not have significantly different
      overall and disease-free breast cancer survival. The shape of association between
      plasma TGF-beta-1 levels and breast cancer survival appears to be non-linear.
      Stratified analysis by stage of disease did not appreciably change the
      association pattern. CONCLUSIONS: We conclude that the relationship between
      circulating levels of TGF-beta-1 and prognosis in breast cancer is complex and
      non-linear. High levels of TGF-beta-1 are associated with worse survival
      independent of stage of disease.

PMID- 18075786
TI  - Economic evaluation of 21-gene reverse transcriptase-polymerase chain reaction
      assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast
      cancer in Japan.
AB  - The 21-gene reverse transcriptase-polymerase chain reaction assay with a patented
      algorithm is validated as a good predictor of prognosis and potential benefit
      from adjuvant chemotherapy for lymph-node-negative, estrogen-receptor-positive,
      early-stage breast cancer, while its high cost raises concern about how to
      finance it. Cost-effectiveness analysis comparing prevalent National
      Comprehensive Cancer Network (NCCN) guideline/St Gallen recommendation-guided
      treatment with the assay-guided treatment is carried out with budget impact
      estimation in the context of Japan's health care system. Incremental cost
      effectiveness ratios are estimated as 2,997,495 yen/QALY (26,065 US$/QALY) in the
      comparison between NCCN guided-treatment vs. the assay-guided treatment, and as
      1,239,055 yen/QALY (10,774 US$/QALY) in the comparison between St Gallen guided
      treatment vs. the assay-guided treatment. Budget impact is estimated as yen2,638
      million (US$23 million) to yen3,225 million (US$28 million) per year. The routine
      use of the assay is indicated as cost-effective. And the budget impact could be
      judged as within fundable level.

PMID- 18075789
TI  - General aspects of the genetics of SLE.
AB  - The application of genetic techniques to the study of systemic lupus
      erythematosus (SLE) has identified candidate genes with diverse immunological
      function. There is a growing understanding that susceptibility to SLE is due to a
      complex interaction of multiple genes and environmental factors, and that many of
      these may be shared with other autoimmune diseases. In this first of a series of
      review articles we outline our current understanding of SLE genetics, in
      particular summarising the results of recent association studies.

PMID- 18075787
TI  - Does acromegaly enhance mortality?
AB  - The increased mortality associated with acromegaly was first demonstrated in
      early epidemiological studies. Since the seminal paper by Wright et al. in 1970,
      nearly 20 studies have analyzed mortality rates in over 5,000 patients with
      acromegaly. Overall standardized mortality rates are approximately two times
      higher than in the general population, relating to an average reduction in life
      expectancy of around 10 years. The excess deaths are due predominantly to
      cardiovascular, cerebrovascular and respiratory disease. Malignancy deaths have
      been high in some studies but not others; in the largest series looking at cancer
      mortality in acromegaly, overall cancer deaths were not increased, but colon
      cancer mortality was higher than expected. In 1993, Bates et al. first
      demonstrated that outcome was related to the latest measurable growth hormone
      (GH), and treatment to reduce GH levels led to improved outcomes. Other factors
      predicting poor outcome include the presence of hypertension and diabetes. On the
      basis of current evidence, a latest GH of less than 2-2.5 mug/L is a better
      predictor of good outcome than a normal insulin-like growth factor-1 (IGF-1),
      possibly due to discrepancy between GH and IGF-1 at low GH levels. There is some
      evidence to suggest a more stringent GH cut-off (less than 1 mug/L) may yield
      additional benefit but further studies are required to investigate any added risk
      of increased mortality from hypopituitarism. Radiotherapy has been linked
      specifically to cerebrovascular mortality and its use in patients with acromegaly
      must involve a careful risk-benefit analysis in each case.

PMID- 18075790
TI  - Complement deficiencies and systemic lupus erythematosus.
AB  - The complement system involves both the innate and the adaptive immune systems
      and has important roles in the pathogenesis of SLE. Complement deficiencies
      within the classical pathway (C1q, C4 and C2) of activation predispose for
      development of the autoimmune disease SLE. The association between complement
      deficiencies and SLE could be explained by several mechanisms, including impaired
      clearance of immune complexes and impaired handling of apoptotic cells, aberrant
      tolerance induction or changes in cytokine regulation. Also during SLE disease
      flares, the complement system is activated giving rise to partial deficiency or
      dysfunction due to consumption. On the other hand, complement also takes part in
      the inflammatory reaction in the disease that gives rise to the tissue and organ
      damage. In this review various aspects of the relation between complement and SLE
      are discussed.

PMID- 18075791
TI  - Fc receptor genes and the systemic lupus erythematosus diathesis.
AB  - Fc receptors represent a distinct group of hematopoeitic cell surface
      glycoproteins that have a characterized role in affecting the efficiency of the
      mononuclear phagocyte system to clear IgG immune complexes. Functional genetic
      variations in this family of receptors have been identified as heritable
      susceptibility factors for SLE and lupus nephritis across diverse populations. In
      this review, we describe the roles of the classical Fc receptors for IgG (Fc
      gamma) and non-classical Fc-like receptors (FCR1-FCRL6L), Fc receptors for IgE
      (Fc epsilon RI) and IgA and IgM (Fc alpha/mu R) in SLE diathesis. The combined
      effects of these genes on SLE pathogenesis, either via linkage disequilibrium or
      epistasis with additional genetic or environmental factors, provide a challenge
      for future investigations. The pursuit of a polygenic SLE-profile that includes
      longitudinal evaluations of SLE and markers involved in the protean clinical
      manifestations associated with SLE will facilitate our understanding of the
      cascade of inflammatory events associated with the diathesis.

PMID- 18075792
TI  - PTPN22: its role in SLE and autoimmunity.
AB  - A functional variant of protein tyrosine phosphatase nonreceptor 22 (PTPN22) has
      recently been shown to be associated with multiple autoimmune diseases, including
      systemic lupus erythematosus (SLE), rheumatoid arthritis, type 1 diabetes, and
      autoimmune thyroid disease. In this review, we discuss the structure and function
      of this gene and its disease-associated polymorphisms. In addition, we review the
      studies investigating the association between this gene and SLE, along with other
      autoimmune diseases.

PMID- 18075793
TI  - The genetics and biology of Irf5-mediated signaling in lupus.
AB  - Recently much attention was attracted to the importance of the type I interferon
      pathway in the initiation and development of the autoimmune disease systemic
      lupus erythematosus (SLE). Many SLE patients have increased serum levels of IFN
      alpha and display an IFN gene expression "signature" characterized by strong
      overexpression of IFN-responsive genes in leukocytes and target tissues.
      Moreover, about 20% of cancer patients treated with IFN-alpha therapy manifest
      symptoms resembling SLE and some later develop the disease. One of the key genes
      of the IFN-alpha pathway, IRF5, was found to be strongly associated with SLE. Two
      functional SNPs lead to alternative splicing and altered steady-state level of
      IRF5 gene expression. Besides, the gene has a polymorphic inserion/deletion in
      exon 6, which contributes to the diversity in the isoform pattern of IRF5.
      Interestingly, recent studies have not found association of IRF5 with the other
      autoimmune diseases, such as rheumatoid arthritis or psoriasis, suggesting the
      unique role for IRF5 in the development of lupus. Here, we present the current
      knowledge on IRF5 genetics and its biological function and discuss the possible
      ways in which IRF5 contributes to susceptibility to SLE.

PMID- 18075794
TI  - Genetics of clinical expression in SLE.
AB  - Systemic lupus erythematosus (SLE) is the prototype of complex autoimmune
      diseases and is characterized by extreme breakdown of self-tolerance which
      results in a wide range of immunologic abnormalities and immune complex
      formation. Genetic, hormonal and environmental factors are known to contribute to
      the expression of the disease. SLE is very heterogeneous in clinical
      manifestations and different autoantibodies may predict different set of clinical
      outcome, however, despite considerable accumulated knowledge, the detailed
      pathogenesis of SLE still remains unknown. In genetic studies, recent findings in
      gene expression analyses strongly support the direct role of cytokines and
      interferons in various immune dysregulations described in SLE. By recent advances
      in high-throughput SNP genotyping, the association studies of this complex
      disease have become more practical and for the first time new genetic association
      results can be confirmed in different population.

PMID- 18075795
TI  - Gene-environment interactions in the aetiology of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a disease that displays a multitude of
      symptoms and a vast array of autoantibodies. The disease course may vary
      substantially between patients. The current understanding of SLE aetiology
      includes environmental factors acting on a genetically prone individual during an
      undetermined time period resulting in autoimmunity and finally surpassing that
      individual's disease threshold. Genetic differences and environmental factors may
      interact specifically in the pathogenetic processes and may influence disease
      development and modify the disease course. Identification of these factors and
      their interactions in the pathogenesis of SLE is vital in understanding the
      disease and may contribute to identify new treatment targets and perhaps also aid
      in disease prevention. However, there are several problems that need to be
      overcome, such as the protracted time frame of environmental influence, time
      dependent epigenetic alterations and the possibility that different pathogenetic
      pathways may result in a similar disease phenotype. This is mirrored by the
      relatively few studies that suggest specific gene-environment interactions. These
      include an association between SLE diagnosis and glutation S-transferase gene
      variants combined with occupational sun exposure as well as variants of the N
      acetyl transferase gene in combination with either aromatic amine exposure or
      hydralazine. With increased knowledge on SLE pathogenesis, the role of
      environmental factors and their genetic interactions may be further elucidated.

PMID- 18075796
TI  - Expression of clock genes in human peripheral blood mononuclear cells throughout
      the sleep/wake and circadian cycles.
AB  - The rhythmic expression of circadian clock genes in the neurons of the
      suprachiasmatic nucleus (SCN) underlies the manifestation of endogenous circadian
      rhythmicity in behavior and physiology. Recent evidence demonstrating rhythmic
      clock gene expression in non-SCN tissues suggests that functional clocks exist
      outside the central circadian pacemaker of the brain. In this investigation, the
      nature of an oscillator in peripheral blood mononuclear cells (PBMCs) is
      evaluated by assessing clock gene expression throughout both a typical sleep/wake
      cycle (LD) and during a constant routine (CR). Six healthy men and women aged
      (mean+/-SEM) 23.7+/-1.6 yrs participated in this five-day investigation in
      temporal isolation. Core body temperature and plasma melatonin concentration were
      measured as markers of the central circadian pacemaker. The expression of HPER1,
      HPER2, and HBMAL1 was quantified in PBMCs sampled throughout an uninterrupted 72
      h period. The core body temperature minimum and the midpoint of melatonin
      concentration measured during the CR occurred 2:17+/-0:20 and 3:24 +/-0:09 h
      before habitual awakening, respectively, and were well aligned to the sleep/wake
      cycle. HPER1 and HPER2 expression in PBMCs demonstrated significant circadian
      rhythmicity that peaked early after wake-time and was comparable under LD and CR
      conditions. HBMAL1 expression was more variable, and peaked in the middle of the
      wake period under LD conditions and during the habitual sleep period under CR
      conditions. For the first time, bi-hourly sampling over three consecutive days is
      used to compare clock gene expression in a human peripheral oscillator under
      different sleep/wake conditions.

PMID- 18075797
TI  - Fluctuations in the concentration of extracellular ATP synchronized with
      intracellular Ca(2+) oscillatory rhythm in cultured cardiac myocytes.
AB  - Isolated and cultured neonatal cardiac myocytes contract spontaneously and
      cyclically. The intracellular concentration of free Ca(2+) also changes
      rhythmically in association with the rhythmic contraction of myocytes (Ca(2+)
      oscillation). Both the contraction and Ca(2+) oscillatory rhythms are
      synchronized among myocytes, and intercellular communication via gap junctions
      has been considered primarily responsible for the synchronization. However, a
      recent study has demonstrated that intercellular communication via extracellular
      ATP-purinoceptor signaling is also involved in the intercellular synchronization
      of intracellular Ca(2+) oscillation. In this study, we aim to elucidate whether
      the concentration of extracellular ATP changes cyclically and contributes to the
      intercellular synchronization of Ca(2+) oscillation among myocytes. In almost all
      the cultured cardiac myocytes at four days in vitro (4 DIV), intracellular Ca(2+)
      oscillations were synchronized with each other. The simultaneous measurement of
      the concentration of extracellular ATP and intracellular Ca(2+) revealed the
      extracellular concentration of ATP actually oscillated concurrently with the
      intracellular Ca(2+) oscillation. In addition, power spectrum and cross
      correlation analyses suggested that the treatment of cultured cardiac myocytes
      with suramin, a blocker of P2 purinoceptors, resulted in the asynchronization of
      Ca(2+) oscillatory rhythms among cardiac myocytes. Treatment with suramin also
      resulted in a significant decrease in the amplitudes of the cyclic changes in
      both intracellular Ca(2+) and extracellular ATP. Taken together, the present
      study demonstrated the possibility that the concentration of extracellular ATP
      changes cyclically in association with intracellular Ca(2+), contributing to the
      intercellular synchronization of Ca(2+) oscillation among cultured cardiac
      myocytes.

PMID- 18075798
TI  - Exposure to T-cycles of 22 and 23 h during lactation modifies the later
      dissociation of motor activity and temperature circadian rhythms in rats.
AB  - Early environmental conditions may affect the development and manifestation of
      circadian rhythms. This study sought to determine whether the maintenance of rats
      under different T-cycles during lactation influences the subsequent degree of
      dissociation of the circadian rhythms of motor activity and core body
      temperature. Two groups of 22 day-old Wistar rats were kept after weaning under T
      cycles of 22 h (T22) or 23 h (T23) for 70 days. Subsequently, they were kept in
      constant darkness (DD). Half of the animals in each group were born and reared
      under these experimental conditions, while the other half were reared until
      weaning under 24 h LD cycles (T24). Rats transferred from T24 to T22 or T23
      showed two circadian components in motor activity and temperature, one entrained
      by light and the other free-running. In T22, there was also desynchronization
      between temperature and motor activity. Rats submitted to T23 from birth showed
      higher stability of the 23 h component than rats transferred from T24 to T23
      after weaning. However, in comparison to rats born under T24 and subsequently
      changed to T22, animals submitted to T22 from birth showed shorter values of the
      period of the non-light-dependent component during T22, more aftereffects when
      transferred to DD, and a lack of desynchronization between motor activity and
      temperature. The results suggest that T-cycles in the early environment may
      modify overt rhythms by altering the internal coupling of the circadian
      pacemaker.

PMID- 18075799
TI  - An inbred lineage of djungarian hamsters with a strongly attenuated ability to
      synchronize.
AB  - An inbred lineage of Ph. sungorus was established at our institute showing some
      unusual characteristics of the circadian system that appear incompatible with an
      adequate adaptation to the periodic environment. We identified a hamster for
      which activity onset was delayed under light-dark conditions (L:D=14:10 h) by
      about 4 h in relation to the light-dark transition. As the activity offset
      remained synchronized with the time of light-on, the activity period (alpha)
      became compressed to 6 h. By means of a special breeding program, the percentage
      of animals showing such a phenomenon increased, indicating that it has a genetic
      component. Also, it is possible now to breed a larger number of hamsters to
      further investigate the rhythm deviations and the underlying mechanisms. Activity
      rhythms were investigated using passive infrared motion sensors. Whereas some of
      the hamsters showed a rather stable phase delay of activity onset relative to the
      onset of darkness, some animals progressively delayed their activity onset up to
      a critical, minimal length of alpha (3.03+/-0.02 h). Thereafter, the rest
      activity rhythm started to free-run with a remarkably long period (tau=25.02 h)
      or became arrhythmic. Some hamsters showed several consecutive cycles alternating
      between a free-running rhythm and entrainment, with increasing tau and reducing
      the phases of temporary entrainment. Finally, these hamsters became arrhythmic.
      The total amount of activity per day was similar in the wild type and delayed
      activity onset hamsters. The latter did increase the intensity of activity,
      thereby compensating for the shorter alpha. The period length in constant
      darkness was significantly longer in the delayed hamsters compared to wild type
      animals (24.37+/-0.03 h vs. 24.24+/-0.02 h; p<0.001). However, this difference
      seems too small to cause the later activity onset. The phase response following a
      light pulse (100 lux, 15' at CT14 where CT12=activity onset) was similar in
      delayed and wild type hamsters (-1.66+/-0.12 h and -1.82+/-0.16 h). As access to
      running wheels is known to influence the circadian pacemaker, particularly to
      strengthen oscillator coupling, a set of further experiments was conducted. The
      free-running period was significantly shorter when the hamsters were provided
      with running wheels (24.25+/-0.04 h and 24.07+/-0.04 h in wild type and delayed
      hamsters, respectively; p<0.005 and p<0.05). However, the effect on the activity
      onset was not unequivocal. In many hamsters it was still delayed, whereas in
      others the unlocking of the wheels led to an expansion of alpha. The described
      inbred lineage appears to be an excellent model to further investigate the
      properties and the interaction of the two oscillators underlying the daily
      activity pattern.

PMID- 18075800
TI  - The effect of experimental diabetes on the twenty-four-hour pattern of the
      vasodilator responses to acetylcholine and isoprenaline in the rat aorta.
AB  - The aim of this study was to investigate whether time-dependent variations in the
      relaxant effect of acetylcholine, an endothelium-dependent vasorelaxant via
      muscarinic receptors, and isoprenaline, a nonselective beta-adrenoceptor agonist
      in rat aorta, are influenced by streptozotocin (STZ)-induced experimental
      diabetes. Adult male rats were divided randomly into two groups: control and STZ
      induced (STZ, 55 mg/kg, intraperitoneal) diabetes. The animals were synchronized
      to a 12:12 h light-dark cycle (lights on 08:00 h) and sacrificed at six different
      times of day (1, 5, 9, 13, 17, and 21 hours after lights on; HALO) eight weeks
      after STZ injection. The in vitro responsiveness of thoracic aorta rings obtained
      from control and diabetic rats to acetylcholine (10(-9)-10(-5) M) and
      isoprenaline (10(-10)-10(-3) M) was determined in six different times. EC(50)
      (the concentration inducing half of the maximum response) values and maximum
      responses were calculated from cumulative concentration-response curves of the
      agonists and were analyzed with respect to time and STZ treatment. Treatment,
      time, and interactions between treatment and time were tested by two-way analysis
      of variance (ANOVA). To analyze differences due to biological time, one-way ANOVA
      was used. STZ treatment did not significantly change EC(50) values or maximum
      responses for both agonists. There were statistically significant time-dependent
      variations in the EC(50) values for isoprenaline and maximum responses for both
      acetylcholine and isoprenaline in control groups by one-way ANOVA, but
      significant time-dependent variations disappeared in the aortas isolated from STZ
      induced diabetic rats. The vasodilator responses to acetylcholine and
      isoprenaline failed to show any significant interaction (treatmentxtime of study)
      between STZ treatment and time of sacrifice in both EC(50) values and maximum
      responses by two-way ANOVA. These results indicate there is a basic temporal
      pattern in the responses to acetylcholine and isoprenaline in rat aorta which
      continues in diabetes. It is shown for the first time that experimental diabetes
      does not change the 24 h pattern of responses to acetylcholine and isoprenaline,
      and that time-dependent variations in the responses to these agonists disappear
      in diabetic animals. Although further studies are required to define the
      underlying mechanism(s) of these findings, results suggest that experimental
      diabetes can modify the time-dependent vasorelaxant responses of rat aorta. This
      may help to understand the circadian rhythms in cardiovascular physiology and
      pathology or in drug effects in diabetes.

PMID- 18075801
TI  - Seasonal rhythms of body temperature in the free-ranging raccoon dog (Nyctereutes
      procyonoides) with special emphasis on winter sleep.
AB  - The raccoon dog (Nyctereutes procyonoides) is the only canid with passive
      overwintering in areas with cold winters, but the depth and rhythmicity of
      wintertime hypothermia in the wild raccoon dog are unknown. To study the seasonal
      rhythms of body temperature (T(b)), seven free-ranging animals were captured and
      implanted with intra-abdominal T(b) loggers and radio-tracked during years 2004
      2006. The average size of the home ranges was 306+/-26 ha, and the average 24 h
      T(b) was 38.0+/-<0.01 degrees C during the snow-free period (May-November). The
      highest and lowest T(b) were usually recorded around midnight (21:00-02:00 h) and
      between 05:00-11:00 h, respectively, and the range of the 24 h oscillations was
      1.2+/-0.01 degrees C. The animals lost approximately 43+/-6% of body mass in
      winter (December-April), when the average size of the home ranges was 372+/-108
      ha. During the 2-9-wk periods of passivity in January-March, the average 24 h
      T(b) decreased by 1.4-2.1 degrees C compared to the snow-free period. The raccoon
      dogs were hypothermic for 5 h in the morning (06:00-11:00 h), whereas the highest
      T(b) values were recorded between 16:00-23:00 h. The range of the 24 h
      oscillations increased by approximately 0.6 degrees C, and the rhythmicity was
      more pronounced than in the snow-free period. The ambient temperature and depth
      of snow cover were important determinants of the seasonal T(b) rhythms. The
      overwintering strategy of the raccoon dog resembled the patterns of winter sleep
      in bears and badgers, but the wintertime passivity of the species was more
      intermittent and the decrease in the T(b) less pronounced.

PMID- 18075802
TI  - The effects of circadian rhythmicity and time-awake on a simple motor task.
AB  - The aim of the study was to assess if a simple motor task, one that required
      muscle contractions well below maximum, showed evidence of circadian changes and
      time-awake. The task consisted of using a larger counter to flick a number of
      smaller counters to land as near as possible to the center of a target. The
      closer a counter landed next to the center of the target, the higher the score
      obtained. Two distances from the target were used (long and short), and 20
      counters were flicked at each distance. The task was performed by 72 diurnally
      active healthy participants at six test sessions distributed every 4 h throughout
      the day (08:00 h, 12:00 h, ... , 04:00 h), so covering a circadian cycle. When
      performing the sessions, subjects had been awake for about 1, 4, ... , 20 h.
      Before each test session, sublingual temperature was measured, and estimates of
      the individual's fatigue and alertness were made. Clear normally phased circadian
      rhythms (p<0.0001) in oral temperature and alertness with mean peak time (i.e.,
      acrophases of 17.2 h and 15.9 h, respectively) and fatigue (i.e., mean acrophase
      of 3.4 h) were detected. The total scores for both the long and short distances
      also showed circadian rhythms that peaked slightly before the temperature rhythm
      (by 2.31+/-0.91 h and 1.77+/-0.77 h, mean+/-SE, respectively), and the number of
      occasions that the target was missed altogether showed rhythms that were in anti
      phase (mean acrophases=3.8 h and 4.1 h for the long and short distances,
      respectively) to that of total scores (mean acrophases=16.0 h and 15.2 h for the
      long and short distances, respectively). With the long and, particularly, short
      distances, there were generally significant correlations (r<0.0005) between both
      the measures of accuracy (total score and number of misses) and body temperature
      and time-awake. The accuracy of performance at this task seems to show circadian
      and time-awake effects, and so makes it of potential value in protocols where
      repetitive measurements during the course of a day are required.

PMID- 18075803
TI  - Light-induced melatonin suppression in humans with polychromatic and
      monochromatic light.
AB  - The relative contribution of rods, cones, and melanopsin to non-image-forming
      (NIF) responses under light conditions differing in irradiance, duration, and
      spectral composition remains to be determined in humans. NIF responses to a
      polychromatic light source may be very different to that predicted from the
      published human action spectra data, which have utilized narrow band
      monochromatic light and demonstrated short wavelength sensitivity. To test the
      hypothesis that only melanopsin is driving NIF responses in humans, monochromatic
      blue light (lambda(max) 479 nm) was matched with polychromatic white light for
      total melanopsin-stimulating photons at three light intensities. The ability of
      these light conditions to suppress nocturnal melatonin production was assessed. A
      within-subject crossover design was used to investigate the suppressive effect of
      nocturnal light on melatonin production in a group of diurnally active young male
      subjects aged 18-35 yrs (24.9+/-3.8 yrs; mean+/-SD; n=11). A 30 min light pulse,
      individually timed to occur on the rising phase of the melatonin rhythm, was
      administered between 23:30 and 01:30 h. Regularly timed blood samples were taken
      for measurement of plasma melatonin. Repeated measures two-way ANOVA, with
      irradiance and light condition as factors, was used for statistical analysis (n=9
      analyzed). There was a significant effect of both light intensity (p<0.001) and
      light condition (p<0.01). Polychromatic light was more effective at suppressing
      nocturnal melatonin than monochromatic blue light matched for melanopsin
      stimulation, implying that the melatonin suppression response is not solely
      driven by melanopsin. The findings suggest a stimulatory effect of the additional
      wavelengths of light present in the polychromatic light, which could be mediated
      via the stimulation of cone photopigments and/or melanopsin regeneration. The
      results of this study may be relevant to designing the spectral composition of
      polychromatic lights for use in the home and workplace, as well as in the
      treatment of circadian rhythm disorders.

PMID- 18075804
TI  - Impact of hypobaric hypoxia in pressurized cabins of simulated long-distance
      flights on the 24 h patterns of biological variables, fatigue, and clinical
      status.
AB  - Long-distance flights can cause a number of clinical problems in both passengers
      and crewmembers. Jet lag as well as mild hypoxia resulting from incomplete cabin
      pressurization could contribute to these problems. The objective of this study
      was to assess, using a chronobiological approach, the clinical impact of diurnal
      hypobaric, hypoxic exposure on fatigue and other common symptoms encountered
      during high-altitude exposure and to measure changes in blood chemistry (i.e.,
      plasma creatinine, urea, uric acid, sodium, calcium, phosphorus, glycemia, and
      lipids). Fourteen healthy, diurnally active (from 07:00 to 23:00 h) male
      volunteers, aged 23 to 39 yrs, spent 8.5 h in a hypobaric chamber (08:00 to 16:30
      h), at a simulated altitude of 8,000 ft (2,438 m). This was followed by an
      additional 8.5 h of study four weeks later at a simulated altitude of 12,000 ft
      (3,658 m). Clinical data were collected every 2 h between 08:00 and 18:00 h, and
      biological variables were assayed every 2 h over two (control and hypoxic
      exposure) 24 h cycles. Clinical symptoms were more frequent with the 12,000 ft
      exposure. Wide interindividual variability was observed in the clinical tolerance
      to prolonged hypobaric hypoxia. The 24 h profiles of most biochemical variables
      were significantly altered at each altitude, with changes in mean plasma levels
      and a tendency toward phase delay, except for uric acid, which showed a phase
      advance. Changes in appetite mainly occurred with the simulated 12,000 ft
      exposure and may have been associated with changes in the postprandial glycemia
      profile. Finally, though the observed biochemical changes were significant, their
      clinical relevance must be clarified in studies involving actual long-distance
      flights.

PMID- 18075805
TI  - Effect of time-of-day-specific strength training on serum hormone concentrations
      and isometric strength in men.
AB  - A time-of-day influence on the neuromuscular response to strength training has
      been previously reported. However, no scientific study has examined the influence
      of the time of day when strength training is performed on hormonal adaptations.
      Therefore, the primary purpose of this study was to examine the effects of time
      of-day-specific strength training on resting serum concentrations and diurnal
      patterns of testosterone (T) and cortisol (CORT) as well as maximum isometric
      strength of knee extensors. Thirty eight diurnally active healthy, previously
      untrained men (age 20-45 yrs) underwent a ten-week preparatory strength training
      period when sessions were conducted between 17:00-19:00 h. Thereafter, these
      subjects were randomized into either a morning (n=20, training times 07:00-09:00
      h) or afternoon (n=18, 7:00-19:00 h) training group for another ten-week period
      of time-of-day-specific training (TST). Isometric unilateral knee extension peak
      torque (MVC) was measured at 07:00, 12:00, 17:00, and 20:30 h over two
      consecutive days (Day 1 & Day 2) before and after TST. Blood samples were
      obtained before each clock-time measurement to assess resting serum T and CORT
      concentrations. A matched control group (n=11) did not train but participated in
      the tests. Serum T and CORT concentrations significantly declined from 07:00 to
      20:30 h on all test days (Time effect, p<.001). Serum CORT at 07:00 h was
      significantly higher on Day 1 than Day 2 in the control and afternoon group, both
      in Pre and Post conditions (Day x Time interaction, p<.01). In the morning group,
      a similar day-to-day difference was present in the Pre but not Post conditions
      (Time x Group interaction, p<.05). MVC significantly increased after TST in both
      the morning and afternoon groups (Pre to Post effect, p<.001). In both groups, a
      typical diurnal variation in MVC (Time effect, p<.001) was found, especially on
      Day 2 in the Pre condition, and this feature persisted from Pre to Post in the
      afternoon group. In the morning group, however, diurnal variation was reduced
      after TST on both Day 1 and Day 2 (Pre to PostxDay x TimexGroup interaction,
      p<.05). In conclusion, 10 weeks of morning time-of-day-specific strength training
      resulted in reduced morning resting CORT concentrations, presumably as a result
      of decreased masking effects of anticipatory psychological stress prior to the
      morning testing. The typical diurnal pattern of maximum isometric strength was
      blunted by the TST period in the morning but not the afternoon group. However,
      the TST period had no significant effect on the resting total T concentration and
      its diurnal pattern and on the absolute increase in maximum strength.

PMID- 18075806
TI  - Alterations of the characteristics of the circadian rest-activity rhythm of
      cancer in-patients.
AB  - The aim of the present study was to evaluate the characteristics of the circadian
      rest-activity rhythm of cancer patients. Thirty-one in-patients, consisting of 19
      males and 12 females, were randomly selected from the Regional Cancer Center,
      Pandit Jawaharlal Nehru Medical College, Raipur, India. The rest-activity rhythm
      was studied non-invasively by wrist actigraphy, and compared with 35 age-matched
      apparently healthy subjects (22 males and 13 females). All subjects wore an
      Actiwatch (AW64, Mini Mitter Co. Inc., USA) for at least 4-7 consecutive days.
      Fifteen-second epoch length was selected for gathering actigraphy data. In
      addition, several sleep parameters, such as time in bed, assumed sleep, actual
      sleep time, actual wake time, sleep efficiency, sleep latency, sleep bouts, wake
      bouts, and fragmentation index, were also recorded. Data were analyzed using
      several statistical techniques, such as cosinor rhythmometry, spectral analysis,
      ANOVA, Duncan's multiple-range test, and t-test. Dichotomy index (I<O) and
      autocorrelation coefficient (r24) were also computed. The results validated a
      statistically significant circadian rhythm in rest-activity with a prominent
      period of 24 h for most cancer patients and control subjects. Results of this
      study further revealed that cancer patients do experience a drastic alteration in
      the circadian rest-activity rhythm parameters. Both the dichotomy index and r24
      declined in the group of cancer patients. The occurrence of the peak (acrophase,
      O) of the rest-activity rhythm was earlier (p<0.001) in cancer patients than age-
      and gender-matched control subjects. Results of sleep parameters revealed that
      cancer patients spent longer time in bed, had longer assumed and actual sleep
      durations, and a greater number of sleep and wake bouts compared to control
      subjects. Further, nap frequency, total nap duration, average nap, and total nap
      duration per 1 h awake span were statistically significantly higher in cancer
      patients than control subjects. In conclusion, the results of the present study
      document the disruption of the circadian rhythm in rest-activity of cancer in
      patients, with a dampening of amplitude, lowering of mean level of activity, and
      phase advancement. These alterations of the circadian rhythm characteristics
      could be attributed to disease, irrespective of variability due to gender, sites
      of cancer, and timings of therapies. These results might help in designing
      patient-specific chronotherapeutic protocols.

PMID- 18075807
TI  - Seasonal modulation of the 8-and 24-hour rhythms of ondansetron tolerance in
      mice.
AB  - Ondansetron (Zophren((R))) is a serotonin 5HT(3)-receptor antagonist used
      primarily to control nausea and vomiting caused by cytotoxic chemo-and radio
      therapy. Tolerance to this drug shows both 24 and 8 h periodicities. In this
      framework, this study aimed to determine whether these ondansetron tolerance
      rhythms are modulated by season. The chronotoxic effect of a fixed dose (3.5
      mg/kg, i.p.) of the drug was investigated with reference to both time of the day
      and year dependencies. Season-related studies were performed on 560 male Swiss
      mice, 10 to 12 wks old, synchronized with L:D=12:12 for three weeks. During a 1
      yr span (2005), four 24 h studies were performed with a single dosing time at 1,
      7, 13, and 19 hours after light onset (HALO), respectively. Tolerance was
      assessed daily during a 40-day span after acute ondansetron treatment. Both
      chi(2) test and cosinor methods were used to analyze the time series data.
      Statistically significant dosing time-dependent changes were validated in both
      yearly and daily time scales. The 24 h mean survival rate peaked in spring (92%)
      compared to fall (72%), the 20% difference being statistically significant
      (chi(2) test with p<0.05 and cosinor with p<0.0001 for seasonal rhythm detection
      and with a peak time, O,=April 3+/-6.6 days). A 24 h rhythm was also detected in
      each of the seasonal time points. However, the curve pattern was monophasic in
      fall as well as spring. In fall, a large amplitude (A) circadian rhythm was
      detected that peaked at 19 HALO, while in the spring, a small circadian rhythm
      was detected that peaked at 1 HALO. The curve pattern was biphasic in summer
      (with large A) and in winter (with a small A). The existence of two peaks of
      equal magnitude in winter (100% survival rate) and in summer (100% and 90%)
      suggests the presence of both circadian and ultradian rhythms rather than an
      ultradian component of the 24 h period. The seasonal modulation of ondansetron
      circadian chronotolerance seems to involve several rhythm parameters: season
      related changes in the 24 h mean (M), amplitude (A), acrophase location (O), as
      well as bimodal curve patterns including the coexistence of rhythms with
      respectively 24 and 8 h periods in winter and summer. In conclusion, tolerance to
      ondansetron varies not only according to the 24 and 8 h periods but also
      according to seasons, which suggests the complexity of ondansetron toxicity
      rhythms. Seasonal modulation of ondansetron tolerance may also influence the
      strategies of chemo-and chrono-therapy, and it is therefore necessary to take it
      into account in clinical drug-delivery protocols to minimize side effects of
      cytotoxic anticancer and antiemetic agents.

PMID- 18075808
TI  - Consistency and accuracy of the Medical Subject Headings thesaurus for electronic
      indexing and retrieval of chronobiologic references.
AB  - The aim of this study was to investigate the reliability of the National Library
      of Medicine (NLM)'s Medical Subject Headings (MeSH) thesaurus for electronic
      indexing and retrieval of published chronobiologic papers. A sample set of 228
      recent chronobiologic references was downloaded from the MEDLINE's database
      together with all MeSH entries associated with them. The following descriptors
      were analyzed among the headings of obvious chronobiologic relevance:
      chronobiology, chronobiology disorders, biological clocks, circadian rhythm,
      chronotherapy, drug administration schedule, periodicity, seasons, sleep
      disorders/circadian rhythm, and time factors. A comparison was made between the
      number of references identified by each heading and the number of articles
      actually pertinent to the same heading (as ascertained after reading each article
      of the sample set). This made possible an assessment of consistency (retrieved
      number not less than actual number) and accuracy (retrieved number not greater
      than actual number) of the usage of each MeSH entry. By reading each article, it
      was also possible to identify common chronobiologic concepts not yet associated
      with specific MeSH headings. In the preselected set of chronobiologic references,
      seasons identified all articles pertinent to seasonal variations and rhythms.
      However, chronobiology disorders missed 97.6% of its pertinent articles;
      periodicity, 95.2%; chronobiology, 87.7%; chronotherapy, 70%; time factors,
      62.3%; and sleep disorders/circadian rhythm, 47.4%. Drug administration schedule
      missed 40% of the chronotherapeutic articles and identified 15% of the
      chronopharmacologic articles; biological clocks missed 24.1% of its pertinent
      articles and wrongly identified 8.3% of the retrieved articles; and circadian
      rhythm missed 2.7% of all circadian studies and wrongly identified 8.2% of the
      articles it retrieved. When used to search chronobiologic articles in the entire
      MEDLINE database, drug administration schedule, seasons, and time factors
      appeared to lack sufficient specificity to produce accurate results. Some common
      chronobiologic concepts were found not to be associated with any specific MeSH
      heading, namely, chronoepidemiology, chronopharmacology, chronotoxicology,
      chronotype, entrainment, and masking. For common chronobiologic concepts and
      definitions, the use of available MeSH headings appears to often yield
      inconsistent and inaccurate results; moreover, the MeSH thesaurus remains
      incomplete.

PMID- 18075809
TI  - Endothelial nitric oxide is not involved in circadian rhythm generation of blood
      pressure: experiments in wild-type C57 and eNOS knock-out mice under light-dark
      and free-run conditions.
AB  - Endothelial nitric oxide synthase knock out mice (eNOS-/-) are mildly
      hypertensive in comparison to wild-type (WT) mice. Hypertension in eNOS-/- mice
      is partly the result of an increase in peripheral resistance due to the absence
      of the vasodilatory action of NO. No data are available for these animals
      regarding the 24 h blood pressure profile under the 12:12 h light-dark cycle (LD)
      and constant dark (DD) conditions. Therefore, this study aimed to investigate by
      radiotelemetry the circadian rhythms in systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) of six eNOS-/- mice and five wild-type mice under
      LD and DD. Data were collected beginning 3 wks after operation (implantation of
      sensor) for 2 wks under LD and for another 2 wks thereafter under DD. Our results
      show that eNOS-/- mice were hypertensive under all experimental conditions. SBP
      and DBP were significantly higher by about 15% in eNOS-/- mice. No differences
      were found in the pattern of the circadian rhythms, rhythmicity, or period
      lengths during LD or DD. The genetic deletion of eNOS seems to lead to higher SBP
      and DBP, but the circadian blood pressure pattern is still preserved with higher
      values during the night (active phase) and lower values during the daytime (rest
      phase). Thus, endothelial-derived NO plays an important role in the regulation of
      vascular tone and haemodynamics, but it is not important for the circadian
      organization of SBP and DBP.

PMID- 18075810
TI  - Seasonal variation in myocardial infarction is limited to patients with ST
      elevations on admission.
AB  - Previous studies have demonstrated seasonal variation in the incidence of acute
      myocardial infarction (AMI) with an increase in cases during the winter months.
      However, they did not assess whether ST-elevation MI (STEMI) and non-ST-elevation
      MI (NSTEMI) exhibit similar changes. The object of this study was to compare the
      seasonal variation of STEMI and NSTEMI. All patients who presented with AMI and
      underwent coronary angiography within seven days of admission were identified via
      the institutional database. STEMI diagnosis required admission ECG demonstrating
      ST elevation in at least two continguous leads. All AMIs not meeting criteria for
      STEMI were defined as NSTEMI. Patients were divided into monthly and seasonal
      groups based on the date of admission with MI. A total of 784 patients were
      included: 549 patients with STEMI and 235 with NSTEMI. When STEMI patients were
      analyzed by season, there were 170 patients (31%) in the winter months, a
      statistically significant difference of excess MI (p<0.005). When NSTEMI patients
      were analyzed, there were 62 patients (26%) in the winter with no statistically
      significant difference in the seasonal variation. Our findings suggest that the
      previously noted seasonal variation in the incidence of AMI is limited to
      patients presenting with STEMI, and that there are important physiological
      differences between STEMI and NSTEMI, the nature of which remains to be
      elucidated.

PMID- 18075811
TI  - Conscientiousness is a predictor of diurnal preference.
AB  - The relationship between diurnal preference, as measured by the Horne-Ostberg
      questionnaire, and quantifiable personality traits was investigated in 617
      participants. A hierarchical multiple regression analysis demonstrated that out
      of the personality variables, conscientiousness was the single biggest predictor
      of diurnal preference (beta=0.246), after controlling for depression, sleep
      disorders, shift work, age, gender, and demographic characteristics. Morningness
      has previously been associated with physiological parameters of the circadian
      clock and with polymorphisms in circadian clock genes, suggesting the possibility
      that conscientiousness, too, may be linked to the same parameters.

PMID- 18075812
TI  - Circadian disruption in shiftwork is probably carcinogenic to humans.

PMID- 18075813
TI  - Ultrasound assessment of articular cartilage: analysis of the frequency profile
      of reflected signals from naturally and artificially degraded samples.
AB  - This article investigates in vitro the hypothesis that the frequency profile of
      ultrasound reflections may be used to characterize degradation and osteoarthritic
      progression in articular cartilage, irrespective of the effects of transducer
      orientation. To this end, ultrasound echoes were taken in the time domain from
      the articular surface and osteochondral junction of normal, collagen meshwork
      disrupted, proteoglycan-depleted, and osteoarthritic samples, converted to the
      frequency domain by fast Fourier transform and analyzed. Our results show the
      significant effects of specific enzymatic degradation programs on the ultrasound
      frequency profile of reflections from the cartilage surface and osteochondral
      junction, and their manifestation in the tissue surrounding a focal
      osteoarthritic defect. Collagen meshwork disruption was most apparent in the
      profile of reflections from the articular surface, while proteoglycan depletion
      was most clearly observed in the reflections from the osteochondral junction. The
      reflected signals from the osteochondral junction may further contain information
      about the subchondral bone. From these results we proposed that the analysis of
      specific frequencies of reflected ultrasound signals has the potential to
      differentiate normal from degraded articular cartilage-on-bone, when the angle of
      incidence can be controlled within a +/-1.2 degrees limit. This encourages
      further research into the effects of progressive artificial degradation of the
      cartilage matrix and subchondral bone on the spectral profile to quantify the
      relationship between the frequency profile and the level of specific degradation
      in naturally degraded joints.

PMID- 18075814
TI  - Calcific tendonitis : a model.
AB  - Calcific tendonitis is a common clinical condition associated with high rates of
      tendon rupture, prolonged symptoms, and poor response to therapy. Little is known
      about the pathogenesis of calcifications in tendons and consequently few
      effective therapies are available. We hypothesized that tendon calcification,
      like pathologic calcification in other sites, was generated by extracellular
      organelles known as matrix vesicles and that isolated matrix vesicles would
      constitute the basis for a useful model of this process. Tendon matrix vesicles
      were isolated from adult porcine patellar tendons using enzymatic digestion and
      differential centrifugation. Vesicle morphology was examined with electron
      microscopy. Levels of calcium, phosphate, pyrophosphate, ATP, and mineralization
      associated enzymes were measured and compared with articular cartilage vesicles
      from porcine articular cartilage. Vesicles were embedded in agarose gels with or
      without type I collagen or dermatan sulfate and incubated in calcifying salt
      solution trace labeled with (45)calcium. (45)Calcium in the vesicle fraction was
      measured after 5-7 days. The type of mineral formed was determined by micro-x-ray
      diffraction. Matrix vesicles isolated from adult porcine tendon were similar
      morphologically to those obtained from articular cartilage. They contained
      mineralization-related enzymes and formed hydroxyapatite mineral in vitro.
      Mineralization was suppressed by levamisole and modulated by extracellular matrix
      components. Matrix vesicles isolated from tendons mineralize in vitro. This model
      may aid in the study of the pathogenesis of calcific tendonitis as well as serve
      as a means to identify effective therapies for this common disorder.

PMID- 18075815
TI  - Recombinant expression, isolation, and proteolysis of extracellular matrix
      secreted phosphoprotein-24 kDa.
AB  - Secreted phosphoprotein-24 kDa (spp24) is an extracellular matrix protein first
      cloned from bone. Bovine spp24 is transcribed as a 203 amino acid residue protein
      that undergoes cleavage of a secretory peptide to form the mature protein (spp24,
      residues 24 to 203). While not osteogenic itself, spp24 is degraded to a pro
      osteogenic protein, spp18.5, in bone. Both spp18.5 and spp24 contain a cyclic
      TRH1 (TGF-beta receptor II homology-1) domain similar to that found in the
      receptor itself and in fetuin. A synthetic peptide corresponding to the TRH1
      domain of spp18.5 and spp24 specifically binds BMP-2 and enhances the rate and
      magnitude of BMP-2-induced ectopic bone formation in vivo. The parental protein,
      spp24, exhibits a high affinity for bone and mineral complexes, but its abundance
      there is low, suggesting that it is rapidly degraded. The availability of
      recombinant spp24 and its degradation products would facilitate the elucidation
      of their structure:function relationships. We describe here the expression of
      His(6)-tagged bovine spp24 (residues 24 to 203) in E. coli, its purification by
      high-resolution IMAC (immobilized metal affinity chromatography), and the
      characterization of the full-length recombinant 21.5 kDa protein and its two
      major 16 kDa and 14.5 kDa degradation products (spp24, residues 24 to 157, and
      spp24, residues 24 to 143) by mass spectroscopy. The recombinant spp24 protein
      was resistant to proteolysis by MC3T3-E1 osteoblastic cell extracts in the
      absence of calcium; however, in the presence of 4 mM Ca, it can undergo
      essentially complete proteolysis to small peptides, bypassing the 16 kDa and 14.5
      kDa intermediates. This confirms the proteolytic susceptibility of spp24. It also
      suggests that the levels of spp24 in bone may be regulated, in part, by calcium
      dependent proteolysis mediated by osteoblastic cells.

PMID- 18075816
TI  - Gingival fibroblasts inhibit MMP-1 and MMP-3 activities in an ex-vivo artery
      model.
AB  - The main arterial pathologies can be associated with a deregulation of remodeling
      involving matrix metalloproteinases (MMPs), whereas gingival healing is
      characterized by an absence of fibrosis or irreversible elastin/collagen
      degradation. The aim of our study was to evaluate the effect of gingival
      fibroblasts on MMP-1 and MMP-3 secretion in an organotypic artery culture. MMP-1
      and MMP-3 secretions and activities (dot blots, zymography, ELISA) were evaluated
      in coculture of rabbit artery in the presence or not of gingival fibroblasts. MMP
      1/TIMP-1 and MMP-3/TIMP-1 complexes forms were measured by ELISA. Complementary
      studies were performed using human aortic smooth muscle cells cocultured with
      adventitial, dermal, or gingival fibroblasts. Our results indicated that MMP-1
      and MMP-3 free-forms activities were significantly reduced in coculture. This
      inhibition was linked to a significant increase of TIMP-1 leading to formation of
      TIMP-1/MMPs complexes. Due to the presence of gingival fibroblasts, the decrease
      in MMP-1 and MMP-3 efficiency thus contributes to diminish the degradation of
      artery. This cellular therapy strategy could be promising in artery pathologies
      treatment.

PMID- 18075817
TI  - The role of transforming growth factor-beta and bone morphogenetic protein with
      fibrin glue in healing of bone-tendon junction injury.
AB  - Bone-tendon junction injuries have poor healing potential. This study evaluated
      the role of TGF-beta and BMP-2 in a fibrin glue carrier in healing of injuries at
      bone-tendon junction. Seventy-two skeletally mature male rabbits were divided
      into 4 groups. The tendo-Achilles was surgically transected at its insertion and
      reattached with a pullout suture. Group 1 served as a control. In groups 2, 3,
      and 4, fibrin glue, a mixture of TGF-beta and fibrin glue, and a mixture of BMP-2
      and fibrin glue were injected into the bone-tendon junction. The animals were
      sacrificed at 2, 4 and 8 weeks after surgical procedure. The addition of TGF-beta
      to fibrin glue did not significantly improve the biomechanical properties of
      repair tissue. BMP-2 in combination with fibrin glue accelerates healing in a
      bone-tendon injury and also improves the histological and biomechanical
      properties of the repair tissue so formed.

PMID- 18075818
TI  - Analysis of human osteoarthritic connective tissue by laser capture
      microdissection and QRT-PCR.
AB  - Gene expression levels for type II collagen and aggrecan have been determined as
      potential measures and disease markers of human osteoarthritis in patients
      undergoing total knee arthroplasty. In this regard, specimens of affected
      articular cartilage obtained intraoperatively at the time of surgery were placed
      in RNAlater(TM) to maintain RNA integrity and subsequently frozen-sectioned.
      Individual or small numbers of chondrocytes were isolated by laser capture
      microdissection and their total RNA was extracted and analyzed by quantitative
      reverse transcription-polymerase chain reaction. Results indicate that type II
      collagen and aggrecan mRNA expression from specific cells in osteoarthritic
      tissues are detectable and reproducible using these approaches. Our work is the
      first to demonstrate successful isolation of RNA limited to chondrocytes
      comprising small quantities of human osteoarthritic material. The study presents
      a new avenue by which the disease and its progression may be critically assayed.

PMID- 18075819
TI  - Modulation of VEGF expression in rat bone marrow stromal cells by GDF-5.
AB  - Angiogenesis is essential for bone formation and several bone morphogenetic
      proteins (BMPs) have been shown to induce angiogenesis through osteoblast-derived
      vascular endothelial growth factor (VEGF)-A. Growth differentiation factor-5 (GDF
      5) is a member of the BMP family expressed in bone and known to induce
      angiogenesis in vivo. In this study, the effects of GDF-5 on osteogenic
      differentiation and expression of VEGF-related genes were determined using rat
      bone marrow stromal cells. GDF-5 stimulated osteogenic differentiation. It also
      upregulated the expression of VEGF-A after 3 hr, accompanied by a trend of
      decrease in its receptor VEGFR-2 at 6 and 24 hr. VEGF-D and its receptor VEGFR-3
      showed peak expression at later time points. This regulation may be further
      controlled by neuropilin 2 that exhibited a parallel profile to VEGF-D. These
      observations indicate that GDF-5 stimulates osteogenic differentiation and has a
      potential to induce angiogenesis through osteoblast-derived VEGF-A in bone.

PMID- 18075820
TI  - Graded arrangement of collagen fibrils in the equine superficial digital flexor
      tendon.
AB  - By using ultramorphological and biochemical methods, we analyzed the regional
      differences between the three parts of the equine superficial digital flexor
      tendon (SDFT), namely, the myotendinous junction (MTJ), middle metacarpal (mM),
      and osteotendinous junction (OTJ). Cross-sectional images showed unique
      distributions of collagen fibrils of varying diameters in each region. Small
      collagen fibrils (diameter <100 nm) were distributed predominantly in the MTJ
      region, and the OTJ region was relatively rich in large collagen fibrils
      (diameter >200 nm). In the mM region, the collagen fibrils were intermediately
      distributed between the MTJ and OTJ. The results indicate a graded arrangement of
      collagen fibrils in the tendon. Type V collagen was detected preferentially in
      the MTJ region. Since type V collagen is believed to be one of the collagens
      regulating collagen fibril formation, its possible functionality in the MTJ
      region in terms of fibril formation and fibril arrangement in the tendon has been
      discussed here.

PMID- 18075821
TI  - Abstracts of the XXVII Italian Society for the Study of Connective Tissues (SISC)
      Meeting, Bologna, Italy, 8-10 November 2007.

PMID- 18075823
TI  - Innate host defense functions of secretory leucoprotease inhibitor.
AB  - Chronic lung diseases such as cystic fibrosis and emphysema are characterized by
      a protease burden, an infective process and a dominant proinflammatory profile.
      Secretory leucoprotease inhibitor (SLPI) is a prominent innate immune protein of
      the respiratory tract, possessing serine protease inhibitor activity,
      antibacterial activity, and anti-inflammatory/immunomodulatory activity. In the
      course of this review, the authors highlight the findings from a range of studies
      that illustrate the multiple functions of SLPI and its role in the resolution of
      the immune response.

PMID- 18075824
TI  - The role of the macrophage in lung disease mediated by bacteria.
AB  - Respiratory infections are a major cause of human morbidity and a leading cause
      of death. The lower respiratory tract is a sterile environment and host defense
      is well developed to clear bacteria. This response includes both humeral factors
      and resident and recruited cells. The alveolar macrophage is an integral
      component and its long-lifespan aids function. Following low-dose challenge
      alveolar macrophages clear bacteria from the lung, employing an over-lapping set
      of microbicidal strategies. At a higher-dose the phagocytic capacity of alveolar
      macrophages is overwhelmed but alveolar macrophages help orchestrate the
      inflammatory response. In the resolution phase of infection alveolar macrophages
      contribute to apoptosis induction and clearance of recruited cells. This process
      down-regulates pro-inflammatory cytokine production. Macrophage function is
      controlled by induction of apoptosis. Delayed-onset macrophage apoptosis
      contributes both to bacterial clearance and to resolution of the inflammatory
      response. Mcl-1, an anti-apoptotic protein with a very short half-life, is a key
      regulator of macrophage survival and therefore of host responses to common
      bacterial pathogens in the lung. Studies involving Streptococcus pneumoniae and
      other respiratory bacteria are discussed to illustrate these points and ephasise
      that the timing of macrophage apoptosis is important in determining its overall
      effect on the host pathogen interaction.

PMID- 18075825
TI  - Interleukin-17 in pulmonary host defense.
AB  - Interleukin (IL)-17A and IL-17F are produced by a novel class of effector
      alphabeta T cells called Th17 cells as well as gammadelta T cells. alphabeta IL
      17-producing T cells are controlled by the transcription factor RORgammat and
      develop independent of GATA-3, T-bet, Stat 4, and Stat 6. Effector molecules
      produced by these cells include IL-17A, IL-17F, and IL-22. IL-17A and IL-17F bind
      to IL-17 receptor (IL-17R) and receptor signaling is critical for host defense
      against extracellular bacteria by regulating chemokine gradients for neutrophil
      emigration into infected tissue sites as well as via regulation of host
      granulopoiesis. Furthermore, it has recently been shown that IL-17 and IL-22
      regulate the production of antimicrobial proteins in epithelium. Although Th17
      cells are important in mucosal host defense, in the setting of retained antigenic
      stimulation, such as in the setting of asthma or chronic infection, such as in
      cystic fibrosis, or in the setting of autoimmunity, these cells can mediate
      immunopathology.

PMID- 18075826
TI  - Neutrophil apoptosis in infectious disease.
AB  - Apoptosis, or programmed cell death, is a highly conserved cellular suicide
      mechanism. Apoptosis is critical to the effective resolution of inflammation,
      particularly in regulating the lifespan of the inflammatory neutrophil.
      Pathological dysregulation of neutrophil apoptosis prevents resolution of
      inflammation and is implicated in numerous inflammatory conditions. Similarly,
      subversion of this critical host defense mechanism by pathogens can prevent
      resolution of infection. Below, we describe the effects of different bacterial
      pathogens on regulation of neutrophil apoptosis and consider how re-engagement of
      these subverted mechanisms may facilitate the development of new strategies to
      combat infectious diseases.

PMID- 18075827
TI  - Host defenses against respiratory tract infection: implications for anti
      inflammatory drug development and treatment.
AB  - The human respiratory tract is exposed to a constantly changing environment which
      may bring it into contact with a variety of pathogenic organisms. A range of
      innate and acquired defence mechanisms have evolved to counter these threats.
      Several new classes of therapeutic agent which may interfere with these defence
      mechanisms have recently been marketed or are under clinical development; this
      paper reviews some key examples, with the potential implications for disease
      management.

PMID- 18075828
TI  - The role of epithelial beta-defensins and cathelicidins in host defense of the
      lung.
AB  - The continuous exposure of the epithelial surface of the conducting airways to
      inhaled pathogens requires the presence of an efficient innate immune system to
      prevent infections. The innate immune system of the lung provides protection
      against a broad spectrum of microbial threats through a variety of effector
      mechanisms. The antimicrobial peptides and proteins form important elements of
      this defence system in the lung. Defensins and cathelicidins are the main
      families of antimicrobial peptides (AMPs) that are present in airway secretions
      and that are expressed by the airway epithelium. Expression and release of these
      small (3-5 kDa) cationic peptides is regulated by exposure of epithelial cells to
      a wide variety of substances, including microbial products, cytokines and growth
      factors. More recently, also active vitamin D(3) has been implicated as a major
      regulator of AMPs expression. AMPs contribute to host defence through direct
      antimicrobial activity, as well as by modulating innate and adaptive immunity,
      and wound repair. Novel insight into the mechanism of action of these peptides
      and the regulation of their expression may lead to innovative approaches for
      treatment of infectious and inflammatory lung disorders.

PMID- 18075829
TI  - Innate immunity in respiratory syncytial virus bronchiolitis.
AB  - Respiratory syncytial virus (RSV) bronchiolitis is a serious and distressing
      illness, which occurs almost exclusively in infants under one year of age.
      Although the majority of all children will have experienced an infection with RSV
      by the time they reach their second birthday, only a minority develop
      bronchiolitis. It is unclear why some otherwise healthy infants develop this
      severe illness and many studies have investigated whether or not this relates to
      an over-exuberant immunological response to the infection. It is increasingly
      being recognized that the innate immune response may play a key role.

PMID- 18075830
TI  - Modeling inflammation in the zebrafish: how a fish can help us understand lung
      disease.
AB  - Neutrophilic inflammation is responsible for much of the tissue damage seen in
      many lung diseases. For resolution of inflammation to occur, neutrophils must die
      by apoptosis, allowing their recognition and removal by macrophages. The
      molecular events controlling this important regulatory step are poorly
      understood, in large part due to the genetic intractability of the human
      neutrophil granulocyte. The authors have established a model of inflammation in
      the Zebrafish, which shares many features of the innate immune system with those
      of humans. Injury to the Zebrafish tailfin induces a reproducible and
      quantifiable inflammatory response, which resolves with kinetics similar to
      mammalian models of neutrophilic inflammation, including pulmonary inflammation.
      Pharmacological modulation of neutrophil apoptosis can modulate the outcome of
      experimentally induced inflammation. In addition, the authors have generated a
      construct that expresses green fluorescent protein under the myeloperoxidase
      promoter, allowing in vivo visualization of neutrophils during experimentally
      induced inflammation. The authors are also performing an unbiased forward genetic
      screen for mutants with defective resolution of inflammation, and to date have
      identified a number of putative mutants. Further study and characterization of
      these mutants is underway. The authors have thus established an important
      experimental link between apoptosis and resolution of inflammation in an in vivo
      system, and defined an important new model for the study of inflammation
      resolution. The authors hope that these tools will permit detailed study of the
      genetic controls of the resolution of inflammation, and provide insights with
      potential clinical utility.

PMID- 18075831
TI  - Upper limb amelia, facial clefts, holoprosencephaly, and interrupted aortic arch.
AB  - The combination of bilateral brachial amelia, facial clefting, and
      holoprosencephaly is rare. To our knowledge, only 4 patients with this
      combination of malformations have been described so far. We report on a male
      fetus with bilateral brachial amelia, complex facial clefts, frontal
      craniosynostosis and hypoplasia, thoracic kyphoscoliosis, and holoprosencephaly.
      In addition, an interrupted aortic arch, a muscular ventricular septal defect,
      and localized noncompaction of the septal myocardium were present. Although
      fibroblast culture was not successful, fluorescent in situ hybridization of
      paraffin-embedded tissue showed a normal set of chromosomes 13, 18, 21, X and Y.
      Our observation supports the hypothesis that this malformation combination may
      constitute a distinct entity. However, so far, a genetic defect remains to be
      identified.

PMID- 18075832
TI  - Fetal and neonatal neuroblastoma: retrospective review of 271 cases.
AB  - Neuroblastoma is the foremost malignant neoplasm of the fetus and neonate. The
      tumor is unique because of its distinctive biologic behavior and many different
      clinical manifestations. The purpose of this review is to focus on the fetus and
      neonate to determine the various ways perinatal neuroblastomas differ clinically
      and morphologically and in their treatment from those found in the older child to
      show that some forms of the tumor have a better outcome than others. The report
      attempts to evaluate the influence of site, histology, stage, biologic markers,
      and treatment on survival.

PMID- 18075833
TI  - Spinal teratoma with pulmonary differentiation: a report of rare case and review
      of literature.
AB  - The occurrence of intradural spinal teratomas in association with spinal
      dysraphism is uncommon and even rarer is pulmonary differentiation in a teratoma.
      We report a case of spinal dysraphism, duplication of lumbosacral spine, split
      cord malformation (SCM I), and meningomyelocele in an 8-month-old child. Excision
      of meningomyelocele and detethering of cord was done. Pathologic examination
      revealed a mature teratoma with pulmonary differentiation. To the best of our
      knowledge this is the second case of spinal teratoma with pulmonary
      differentiation.

PMID- 18075834
TI  - Immunohistochemical nuclear positivity for WT1 in childhood acute myeloid
      leukemia.
AB  - Several studies have reported previously that acute myeloid leukemia (AML) may
      express WT1 detected by RT-PCR and/or Northern blotting. The diagnostic utility
      of WT1 expression in AML using immunohistochemistry has not been reported
      previously. Paraffin-embedded tissue sections from 55 AML, 12 acute lymphoblastic
      leukemia (ALL), and 10 normal bone marrow specimens were immunostained for WT1
      (anti-N terminus antibody). 22/55 AML cases (40%) demonstrated nuclear
      immunopositivity for WT1, including 20/47 bone marrow trephines and 2/4
      granulocytic sarcomas. All the ALL and normal bone marrow specimens were
      negative. A significant proportion of AML expresses nuclear immunostaining for
      WT1, a finding that has only been described previously in Wilms' tumor and
      desmoplastic small round cell tumor. This finding is important for the correct
      interpretation of immunohistochemical findings in the diagnosis of "small round
      cell" tumors of childhood, especially in cases of extramedullary deposits of AML,
      in which traditional myeloid markers may be negative.

PMID- 18075835
TI  - Sudden infant death syndrome and activating GNAS1 gene mutations.
AB  - GNAS1 gene mutations cause the McCune-Albright syndrome. Some patients may
      develop unusual, severe, nonendocrine manifestations that may lead to death. We
      postulate that some cases of sudden infant death syndrome (SIDS) might be caused
      by GNAS1 gene mutations affecting vital organs. We studied two GNAS1 gene
      mutations (R201H and R201C) by allele specific PCR and enzymatic digestion in
      pulmonary, pancreas, liver, kidney, and heart tissue from 29 infants who suffered
      SIDS. The infants died at age 96 +/- 78 days. At the time of death, children had
      a height Z score of -0,04 +/- 0,95, a weight Z score of 0,04 +/- 0,91, and a
      weight for length Z score of 0,1 +/- 0,83. The molecular study by both techniques
      did not reveal any GNAS1 mutations in the tissues examined. We conclude that
      GNAS1 gene mutations do not appear to be present in tissues of infants with SIDS.

PMID- 18075836
TI  - Retinol and retinoic acid increase MMP-2 activity by different pathways in
      cultured Sertoli cells.
AB  - Diseases such as atherosclerosis, arthritis and cancer have been related with
      imbalance in ROS production and failures in regulation of the MMPs. Authors
      suggested a relationship between MPP activity and ROS. Our research group has
      demonstrated that retinol 7 microM induced changes in Sertoli cell metabolism
      linking retinol treatment and oxidative stress. We verified MMP activity in
      Sertoli cells treated with vitamin A using gelatin zymography. We found that
      retinol (7 microM) and retinoic acid (1 nM) induced MMP-2 activity in Sertoli
      cells. Antioxidants reversed retinol-induced but not retinoic acid-induced MMP-2
      activity. Moreover, retinol but not retinoic acid increased ROS production
      quantified by DCFH-DA oxidation. We found that retinol and retinoic acid induced
      ERK1/2 phosphorylation, but only retinol-increased MMP-2 activity was inhibited
      by UO126, an ERK1/2 phosphorylation inhibitor. Our findings suggested that
      retinol-induced MMP-2 activity, but not retinoic acid-induced MMP-2 activity, was
      related to ERK1/2 phosphorylation and ROS production.

PMID- 18075837
TI  - Signal processes and ROS production in glucose transport regulation by
      thrombopoietin and granulocyte macrophage-colony stimulation factor in a human
      leukaemic cell line.
AB  - In M07e cells, a human megakaryocytic leukaemia line, reactive oxygen species
      (ROS) are generated in response to cytokines acting as intracellular messengers
      to modulate glucose transport. The aim of this work was to study the signal
      cascade involved in the acute glucose transport activation in cells exposed to
      growth factors, such as granulocyte macrophage-colony stimulation factor (GM-CSF)
      and thrombopoietin (TPO), to better understand some aspects of the aberrant
      proliferation in leukaemia. Results confirm ROS involvement in modulation of
      glucose transport in this cell line. Furthermore, GM-CSF and TPO produced changes
      in Glut1 phosphorylation and specific inhibitors employed to identify protein
      kinases involved in Glut activation by these cytokines proved that Akt, PLC
      gamma, Syk and the Src family take part in signal transduction leading to Glut1
      activation.

PMID- 18075838
TI  - Changes of nitric oxide, carbon monoxide and oxidative stress in term infants at
      birth.
AB  - The higher risk of respiratory problem in infants delivered by elective caesarean
      section in comparison with vaginally born infants may be favoured by lower level
      of nitric oxide (NO) and carbon monoxide (CO) and higher oxidative stress in
      infants born by caesarean section. We studied healthy term infants born by
      vaginal delivery or by elective caesarean section. Nitric oxide, CO, guanosine 3
      5 cyclic monophosphate, total hydroperoxide and advanced oxidation protein
      products (AOPP) were measured at birth and 48-72 h of life. Nitric oxide, CO and
      cGMP were lower at birth and at 48-72 h of life in infants born by elective
      caesarean delivery. Total hydroperoxide and AOPP levels were similar in the two
      groups and increased from birth to 48-72 h of life. In conclusion, nitric oxide
      and CO concentrations were higher in term infants vaginally born than in infants
      born by elective caesarean section and decreased from birth to 48-72 h of life.
      The mode of delivery did not affect the oxidative stress which increases from
      birth to 48-72 h of life.

PMID- 18075839
TI  - Microcirculation and oxidative stress.
AB  - The microcirculation is a complex and integrated system, transporting oxygen and
      nutrients to the cells. The key component of this system is the endothelium,
      contributing to the local balance between pro and anti-inflammatory mediators,
      hemostatic balance, as well as vascular permeability and cell proliferation. A
      constant shear stress maintains vascular endothelium homeostasis while perturbed
      shear stress leads to changes in secretion of vasodilator and vasoconstrictor
      agents. Increased oxidative stress is a major pathogenetic mechanism of
      endothelial dysfunction by decreasing NO bioavailability, promoting inflammation
      and participating in activation of intracellular signals cascade, so influencing
      ion channels activation, signal transduction pathways, cytoskeleton remodelling,
      intercellular communication and ultimately gene expression. Targeting the
      microvascular inflammation and oxidative stress is a fascinating approach for
      novel therapies in order to decrease morbidity and mortality of chronic and acute
      diseases.

PMID- 18075840
TI  - Gamma-glutamyltransferase is upregulated after oxidative stress through the Ras
      signal transduction pathway in rat colon carcinoma cells.
AB  - Gamma-glutamyltransferase (GGT) plays a central role in the homeostasis of the
      antioxidant glutathione (GSH). The expression of GGT has been shown to be
      upregulated after oxidative stress, but the signalling pathways implicated remain
      poorly characterized. The results here show that acute exposure of CC531 cells to
      oxidative stress resulted in activation of Ras and augmented GGT enzyme activity,
      both at the transcriptional and at the translation level. Moreover, an
      involvement of the GGT promoter II was detected after RT-PCR and transient
      transfection studies. Ectopic expression of activated Ras, but not dominant
      negative Ras, also resulted in increased GGT promoter II transcriptional
      activity, an effect that was attenuated by over-expression of dominant negative
      mutants of Akt, p38 MAPK and MEK1. Addition of specific inhibitors of these
      kinases during oxidative stress diminished the activation of GGT. In conclusion,
      oxidative stress-induced activation of GGT involves Ras and several downstream
      signalling pathways.

PMID- 18075842
TI  - A comparison of 19th century and current attitudes to female sexuality.
AB  - The 19th century medical attitude to normal female sexuality was cruel, with
      gynecologists and psychiatrists leading the way in designing operations for the
      cure of the serious contemporary disorders of masturbation and nymphomania. The
      gynecologist Isaac Baker Brown (1811-1873) and the distinguished endocrinologist
      Charles Brown-Sequard (1817-1894) advocated clitoridectomy to prevent the
      progression to masturbatory melancholia, paralysis, blindness and even death.
      Even after the public disgrace of Baker Brown in 1866-7, the operation remained
      respectable and widely used in other parts of Europe. This medical contempt for
      normal female sexual development was reflected in public and literary attitudes.
      Or perhaps it led and encouraged public opinion. There is virtually no novel or
      opera in the last half of the 19th century where the heroine with 'a past'
      survives to the end. H. G. Wells's Ann Veronica and Richard Strauss's Der
      Rosenkavalier, both of which appeared in 1909, broke the mould and are important
      milestones. In the last 50 years new research into the sociology, psychology and
      physiology of sexuality has provided an understanding of decreased libido and
      inadequate sexual response in the form of hypoactive sexual desire disorder. This
      is now regarded as a disorder worthy of treatment, either by various forms of
      counseling or by the use of hormones, particularly estrogens and testosterone.

PMID- 18075843
TI  - Menopause: developing a rational treatment plan.
AB  - In recent years, growing importance has been afforded to assisting women in
      coping with the menopausal transition. Menopause is a normal stage of development
      and a woman's attitude toward this transition embodies biological, psychological
      and social influences. An enlarging body of conflicting data concerning
      menopausal hormone therapy (MHT) demands reassessment of established paradigms of
      disease prevention and menopausal health. Currently, a woman's decision to
      participate in or abstain from menopausal HT is personal. It involves not only
      consideration of risk stratification of potential harm and benefit, but also
      involves her expectations and attitudes toward perceived physical and emotional
      changes associated with this change. Through the use of extensive patient
      history, quality-of-life questionnaires and powerful biological profiling, we may
      be able to develop a rational approach to menopausal HT that safely guides our
      patients through this transition.

PMID- 18075844
TI  - Advances in hormone replacement therapy: weight benefits of drospirenone, a
      17alpha-spirolactone-derived progestogen.
AB  - Hormone replacement therapy (HRT) remains the most effective treatment for
      menopausal symptom relief, and may provide cardiovascular benefits in younger
      women initiating treatment soon after menopause. However, large surveys indicate
      that many symptomatic women refuse or discontinue HRT prematurely owing to fear
      of weight gain. A continuous combined HRT containing 17beta-estradiol (E(2)) 1 mg
      plus drospirenone (DRSP) 2 mg is effective in relieving menopausal symptoms and
      preventing postmenopausal osteoporosis. DRSP is a unique synthetic progestogen
      with a pharmacological profile similar to that of natural progesterone, including
      antialdosterone activity, a property not exhibited by other synthetic
      progestogens. DRSP can therefore reduce estrogen-related sodium and water
      retention in postmenopausal women receiving HRT via the renin-angiotensin
      aldosterone system, which regulates sodium and water balance. This may translate
      into weight benefits. Pooled data from two placebo-controlled clinical trials (n
      = 333) indicated statistically significant weight loss of -1.5 kg at 6 and 12
      months in postmenopausal women receiving E(2)/DRSP vs. placebo (p < 0.001). In a
      third randomized controlled trial (n = 1147), women receiving E(2)/DRSP
      maintained or lost weight, whereas weight increases were observed in women
      receiving E(2) monotherapy (p < 0.0125). E(2)/DRSP could help maintain or even
      slightly decrease body weight during treatment, potentially improving HRT
      acceptance and compliance.

PMID- 18075845
TI  - Polycystic ovary syndrome: a follow-up study on diabetes mellitus, cardiovascular
      disease and malignancy 15-25 years after ovarian wedge resection.
AB  - The aim of the present study was to examine the occurrence of possibly associated
      diseases in 149 women with polycystic ovary syndrome (PCOS) 15-25 years after
      ovarian wedge resection. Diabetes mellitus was the only associated disease which
      showed a significantly increased occurrence. No significant change in cancers
      specific for the female gender was seen. Likewise, the relative risk of
      cardiovascular disease was not affected. However, the power of the statistical
      test was low. This long-term study indicates increased risk of diabetes mellitus
      in PCOS patients. The study group is too small to give any conclusions about
      other possibly associated diseases. Family histories, however, revealed that
      associated diseases are related to genetic disposition rather than to PCOS per
      se.

PMID- 18075846
TI  - Metformin decreases circulating acylation-stimulating protein levels in
      polycystic ovary syndrome.
AB  - AIM: There are no studies that examine the circulating acylation-stimulating
      protein (ASP) levels in patients with polycystic ovary syndrome (PCOS). The
      present study was designed to determine the ASP levels in PCOS and to evaluate
      the effect of metformin on plasma fasting ASP concentrations. METHODS: Twenty
      women with PCOS and 20 healthy controls matched for age and body mass index (BMI)
      were included in the study. We determined ASP and other biochemical parameters
      before and after treatment. RESULTS: Baseline levels of plasma ASP, complement 3
      (C3), waist-to-hip ratio (WHR), homeostasis model assessment-insulin resistance
      index (HOMA-IR), fasting insulin, triglycerides (TG) and very-low-density
      lipoprotein cholesterol (VLDL-C) were significantly higher in patients than in
      controls. After 3 months of metformin treatment, BMI, WHR, ASP, C3, fasting
      glucose, fasting insulin, HOMA-IR, total cholesterol, TG, VLDL-C and free
      testosterone decreased significantly, whereas apolipoprotein A-I and high-density
      lipoprotein cholesterol increased significantly. CONCLUSIONS: The major novel
      information of the present study is that ASP and C3 values are markedly increased
      in non-obese patients with PCOS, with a decrease evidenced with metformin
      treatment.

PMID- 18075848
TI  - Effect of Biophytum sensitivum on cell-mediated immune response in mice.
AB  - Effect of Biophytum sensitivum on cell-mediated immune response was studied in
      normal as well as Ehrlich ascites tumor bearing BALB/c mice. Administration of
      Biophytum sensitivum significantly enhanced the proliferation of splenocytes,
      thymocytes and bone marrow cells by stimulating the mitogenic potential of
      various mitogens such as Lipopolysaccharide (LPS), Concanavalin A (Con A),
      Phytohaemagglutinin (PHA) and Poke Weed Mitogen (PWM). Natural killer (NK) cell
      activity was enhanced significantly by Biophytum sensitivum in both the normal
      (43.6% cell lysis on day 5) and the tumor bearing group (48.2% cell lysis on day
      5), and it was found to be earlier than tumor bearing control animals (maximum of
      13.4% cell lysis on day 9). Antibody dependent cellular cytotoxicity (ADCC) was
      also enhanced significantly in both Biophytum treated normal (35% cell lysis on
      day 7) as well as tumor bearing animals (40.2% cell lysis on day 7) compared to
      untreated control tumor bearing animals (maximum of 12.3% cell lysis on day 11).
      An early antibody dependent complement mediated cytotoxicity (ACC) was also
      observed in the Biophytum treated normal (22.6% cell lysis, on day 15) and tumor
      bearing animals (26.4% cell lysis, on day 15). Results of our present study
      suggest the immunomodulatory property of Biophytum sensitivum.

PMID- 18075849
TI  - In vivo immunomodulatory effects of aqueous extracts of Larrea divaricata Cav.
AB  - Several medicinal plants are considered immunomodulatory as they display a
      variety of anti-inflammatory, antimicrobial and antitumoral effects. Larrea
      divaricata Cav. (jarilla) (Zygophyllaceae) is a plant widely used in popular
      medicine to treat tumors, infections, and inflammatory diseases. So far, the
      immunostimulating activities of Larrea divaricata have not been studied in vivo.
      In this work, we used healthy mice to assess the immunomodulatory potential of
      aqueous extracts of Larrea divaricata Cav. We found that Decoction (D) and
      Infusion (I) from Larrea divaricata Cav showed any acute hepatotoxic activity.
      Only D at 0.5 mg/kg increased the carrageenan-induced inflammation. Macrophages
      harvested from treated mice showed no signs of apoptosis. These cells showed a
      significant increase in NO and TNF-alpha release and exhibited the strongest
      expression of iNOS. Decoction also increased the phagocytosis of zymosan and the
      binding of LPS-FITC. The expression of CD14, TLR4 and CR3 was lower in
      macrophages of mice treated than in controls. Thus, Larrea divaricata was able to
      prime Mphi in vivo and to induce full activation in vitro. Our finding contribute
      to characterize the biological activity of Larrea divaricata and to understand
      the ability of these extracts to enhance immune responses.

PMID- 18075850
TI  - Cyclosporin-A augments respiratory burst of whole blood phagocytes in pregnant
      rats.
AB  - Both pregnancy and cyclosporin A (CsA) are known to inhibit T-cell mediated
      immune response and to activate phagocytes against microbial infections as a
      compensatory mechanism. Pregnant women, either with organ transplantation or
      suffering from autoimmune diseases, are commonly managed with CsA therapy. This
      investigation was aimed to study effect of CsA on phagocytic activity of whole
      blood polymorphonuclear leukocytes (PMNs) in pregnant rats. Both pregnant and non
      pregnant Sprague-Dawley rats (4 animals per group) were treated with CsA (40
      mg/kg, oral) for 7 days starting from gestation day 7. Respective control groups
      of non-pregnant and pregnant rats received vehicle only. Luminol-dependent
      chemiluminescence (CL) was used to measure the generation of reactive oxygen
      species (ROS) in respiratory burst of whole blood PMNs stimulated by zymosan. The
      results showed a moderate and insignificant increase in CL response in non
      pregnant rats with CsA treatment or pregnant rats without CsA treatment. Whereas
      the CL response of whole blood PMNs was significantly higher (ANOVA F = 35.66, P
      < 0.001) in pregnant rats treated with CsA. In conclusion, this preliminary study
      demonstrates synergistic effects of pregnancy and CsA on activation of PMNs
      resulting in massive and sustained generation of ROS that could be deleterious to
      both host and fetus.

PMID- 18075851
TI  - Construction and expression of single-chain antibody derived from a new clone of
      monoclonal antibody against human CD14 in CHO cells.
AB  - Our aim was to construct the eukaryotic expressional system of single-chain
      antibody (ScFv(2F9)) derived from a new clone of monoclonal antibody named ZCH-7
      2F9 against human CD14 antigen, and to obtain the ScFv(2F9) protein with a high
      biological activity for further studies on ScFv(2F9) immunotoxin and other kinds
      of genetically engineered antibodies. Primers were synthesized according to the
      gene sequence of ScFv(2F9), 4 tandem glysines and 1 serine (Gly4Ser)3 linker and
      multiple cloning site(MCS) of pSectag2A vector, which included SfiI and EcoRI
      enzyme cleaving site, 6 x His and stop code TGA sequences. ScFv(2F9) gene was
      amplified through splicing by overlap extension (SOE) using the high fidelity Taq
      polymerase. Then the gene was cloned to pGEM-T easy and pSectag2A vectors.
      Positive recombinants (pSectag2A/ScFv(2F9)) were identified through enzyme
      cleaving and sequenced before expression. The recombinant plasmids were
      transfected into Chinese hamster ovary (CHO) cells for expression. The relative
      molecular weight (MW) and the binding activity of the interesting protein were
      determined by SDS-PAGE, Western-blot and flow cytometry (FCM), respectively. The
      scFv(2F9) V(H) is a member of the IgH gene family V(1) subgroup and the scFv(2F9)
      V(L) gene belongs to the Ig(kappa) gene family V(10) subgroup. The recombined
      ScFv(2F9) gene was identified to be functional by sequencing and expressing. The
      interesting protein could be detected in the culture supernatant of transformed
      CHO cells with a MW of 31 kDa. The blocking test showed that the positive cell
      percentages, the mean fluorescence intensity (MFI) and the peak of channel (peak
      Ch) were reduced by 90.02%, 63.3%and 63.38%, respectively after blockage of
      ScFv(2F9). The ScFv(2F9) gene was cloned and the interest protein against human
      CD14 antigen has been successfully expressed in eukaryotic cells with a high
      biological activity, which lays the foundation for further studies on its
      immunotoxin and other kinds of engineered antibodies.

PMID- 18075852
TI  - Cannabinoid CB(2)-selective inverse agonist protects against antigen-induced bone
      loss.
AB  - Work to improve the therapeutic properties of cannabinoid CB(2) receptor
      selective inverse agonists has led to the development of Sch.036, an aryl
      substituted triaryl bis-sulfone with improved oral pharmacokinetic parameters. In
      this report, we show that this compound blocks in vivo trafficking of various
      leukocyte populations, a property consistent with other members of this chemical
      series. This CB(2)-selective compound also shows efficacy in leukocyte
      recruitment models when added in concert with suboptimal doses of selected anti
      inflammatory agents, consistent with its unique function and indicative of its
      potential therapeutic utility. Finally, studies with Sch.036 show that this
      cannabinoid CB(2)-specific inverse agonist can ameliorate bone damage in a rat
      model of relapsing-remitting arthritis. This result suggests that a cannabinoid
      CB(2)-selective inverse agonist may help ameliorate a particularly harmful
      property of this inflammatory joint disease.

PMID- 18075853
TI  - Effects of components derived from diesel exhaust particles on lung physiology
      related to antigen.
AB  - Our previous study has shown that diesel exhaust particles (DEP), main
      constituents in ambient particulate matters (PM), enhance airway
      hyperresponsivness in a murine model of allergic asthma (Takano et al., 1998).
      However, it remains unknown which components in DEP are responsible for the
      enhancement. The present study investigated the effects of repeated pulmonary
      exposure to DEP components (extracted organic chemicals in DEP; DEP-OC,
      carbonaceous nuclei of DEP after extraction; washed DEP) on lung physiology in
      the presence or absence of antigen. ICR mice were divided into six experimental
      groups. Vehicle, DEP components, ovalbumin (OVA), or DEP components plus OVA was
      administered intratrachally for 6 weeks. Twenty-four hr after the last
      instillation, cholinergic lung reactivity was examined. DEP components alone did
      not induce any facilitation of lung function as compared to vehicle alone. The
      values of total respiratory system resistance (R), elastance (E), Newtonian
      resistance (R(n)), tissue damping (G), and tissue elastance (H) were higher and
      the value of compliance (C) was lower in the OVA or the DEP component + OVA
      groups than in the vehicle group. In particular, the hyperreactivity was most
      prominent in the washed DEP + OVA group. The values in the DEP-OC + OVA group
      were not significantly different from those in the OVA group. These data suggest
      that carboneous component in DEP, rather than organic chemical one, can be
      attributable to the enhancement of lung hyperresponsiveness in allergic asthma.

PMID- 18075854
TI  - Repeated peripheral administrations of CpG oligodeoxynucleotides lead to
      sustained CNS immune activation.
AB  - Bacterial DNA containing CpG motifs activates cells of the innate immune system.
      In this study, we examined the effects of multiple peripheral bacterial DNA
      mediated CNS innate immune stimulation. To study this issue, we repeatedly
      peripherally administered synthetic CpG-oligodeoxynucleotides (CpG-ODN) and
      assayed effects on CNS-associated TNF-alpha (TNFalpha) and C1q mRNA levels. We
      for the first time accounted for frequency of CpG-ODN administration and time
      kinetics of mRNA expression. We were able show that multiple intraperitoneal CpG
      ODN administrations have a sustainable effect on immune effectors of the brain
      and stimulate TNFalpha mRNA secretion even up to 7 days after the last CpG-ODN
      application. This could on the one hand indicate a depot effect after multiple
      peripheral CpG-ODN administrations, however, it could also indicate that the cell
      producing TNFalpha mRNA remains activated for the indicated time period.
      Furthermore, elevated mRNA levels of C1q were observed, possibly indicating
      microglial activation after multiple peripheral bacterial DNA administrations. In
      this study, we have correlated frequency of CpG-ODN administrations with CNS
      associated TNFalpha mRNA levels and show that multiple peripheral administrations
      of CpG-ODN lead to a sustained level of a Th1-associated cytokine in the brain.
      These findings indicate that the repeated peripherial administration of CpG
      oligodeoxynucleotides offer a therapeutical possibility for CNS-associated
      infections and tumors.

PMID- 18075855
TI  - Suppression of T lymphocyte proliferation to antigenic and mitogenic stimuli by
      Benzo(alpha)pyrene and 2-aminofluorene metabolites.
AB  - Here, we attempt to reveal how 2-aminofluorene (AF), benzo(alpha)pyrene (BP) and
      their major metabolites affect T-cell responses to antigenic and mitogenic
      stimuli. P-450-related metabolism of these parent compounds to metabolites seems
      to precede the observed immunosuppression; therefore, we investigated the
      influence of alpha-naphthoflavone (P-450 inhibitor) and beta-naphthoflavone (P
      450 inducer) on BP and AF immunosuppression. We used proliferative responses to
      concanavalin A and the allogeneic mixed lymphocyte response as correlates of
      immunosuppression. We also attempted to correlate DNA-adduction to the extent of
      observed immunosuppression for AF and BP metabolites. These data show that the
      pathway to the strongest immunosuppressive agents for polycyclic aromatic
      hydrocarbons and arylamines are divergent and related to metabolism by P450
      enzymes.

PMID- 18075856
TI  - Effect of high molecular weight water-soluble chitosan on the trabecular bone and
      thickness in ovariectomized rats.
AB  - High molecular weight water-soluble chitosan(WSC), having an average molecular
      weight of 300,000 Da and a degree of deacethylation over 90%, can be produced
      using a simple multi-step membrane separation process. In this study, the
      trabecular bone area and thickness in ovariectomized(OVX) rats decreased by
      almost 50% from those in sham-operated rats. WSC was evaluated for inhibition of
      the progress of bone loss induced by OVX rats. We measured bone histomorphometry
      in sham, OVX or WSC-administered OVX rats. From light microscopic analyses, a
      porous or erosive appearances were observed on the surface of trabecular bone of
      tibia in OVX rats, whereas those of the same bone in sham-operated rats were
      composed of fine particles. The trabecular bone area and trabecular thickness in
      OVX rats decreased by 50% from those in sham rats, these decreases were
      completely inhibited by administration of WSC at a concentration of 15
      mg/kg/daily for 7 weeks. In this study, the mechanical strength in femur neck was
      significantly enhanced by the treatment of WSC for 7 weeks. In OVX rats, free
      T(3) was normal in all cases, whereas free T(4) was significantly increased.
      Although there was no difference between OVX and WSC-administered rats in T(3)
      level, we have found significant difference between them in T(4) level. These
      results strongly suggest that WSC is effective in preventing the development of
      bone loss induced by OVX in rats.

PMID- 18075857
TI  - Insulin administration confers diabetes-preventive properties to NOD mice derived
      dendritic cells.
AB  - Administration of autoantigen can be of value for prevention of autoimmune
      diabetes and it has been speculated that the control point of dendritic cells
      (DC) for the induction of peripheral tolerance may be highly relevant. We
      examined the properties of DC associated with immune suppression in NOD mice by
      insulin injection subcutaneously and the ability of which to suppress diabetes
      transfer by diabetogenic effector cells in secondary NOD-SCID recipients. Our
      data showed that the surface expressions of MHC II and CD86 on NOD-derived DC
      were increased after insulin treatment compared with those on PBS controlled
      mice. The dendritic cells with a mature phenotype and increased MLR stimulation
      adoptively transferred immune tolerogenic effects in secondary NOD-SCID mice,
      which were associated with significant greater IL-10, TGF-beta production and
      CD4(+)CD25(+)T differentiation from splenocytes compared with NOD-SCID control
      recipients. Moreover, treatment with DC remarkably decreased the incidence of
      diabetes in secondary recipients. These results suggest that a subtype of DC
      generated by insulin subcutaneous treated NOD mice confers potential protection
      from diabetes through polarizing the immune response towards a Th2 regulatory
      pathway.

PMID- 18075858
TI  - Effect of acute pain on splenic NK cell activity, lymphocyte proliferation and
      cytokine production activities.
AB  - Various types of physical and physiological stress in animals have been shown to
      affect their humoral and cell-mediated immune responses. The present study was
      designed to investigate the possible influence of acute pain on the immune
      system. BALB/c mice were exposed to an increasing number of heat shocks using a
      Tail Flick apparatus; an equal number of control mice received no shock
      treatments. After each of the regimens was completed, the spleen of each mouse
      was recovered and various cell populations isolated to assess: the proliferative
      response to phytohemagglutinin by lymphocytes; cytotoxic activities of natural
      killer (NK) cells; and, the production of select important cytokines by splenic
      lymphocytes. The results indicated that NK cell activity and proliferation of
      lymphocytes were significantly (p < 0.001) increased due to the shock regimens
      after only a single day's rounds of stimulation (i.e., 3 rounds of approximately
      12 equally time-spaced shocks/hr with 30-45 min gap between rounds). After 2 and
      3 days' rounds of stimulations, no significant changes were detected in the
      proliferative response of isolated lymphocytes; conversely, the activity of NK
      cells remained significantly elevated compared to the controls hosts' cells, even
      on the second day of stimulation but not on the third. Regarding effects on
      cytokines, no significant changes were detected in the amount of Interferon-gamma
      (IFNgamma) and Interlukin-10 (IL-10) produced by lymphocytes obtained from the
      spleens of any of the shocked mice. These results could suggest that certain
      acute stressors might actually strengthen a host's immunological reactivity and,
      possibly, result in an enhanced capacity to resist pathogens that might infect
      the body.

PMID- 18075859
TI  - Enhancement of antitumor immunity after propofol treatment in mice.
AB  - Propofol and midazolam are the most widely used sedatives in the intensive care
      setting after surgery. We studied whether these sedatives had any antitumor
      immunity effects in mice. Mice were given intraperitoneal injections of propofol
      or midazolam and subcutaneous inoculation of tumor cells (EL4). Then, spleen
      cells were collected and the in vitro activity of cytotoxic T lymphocytes (CTL)
      was measured using flow cytometry. The in vitro activity of CTL against EL4 was
      significantly greater after propofol injection compared with its vehicle
      (Intralipid) or saline. Midazolam had no effect on CTL activity. We also studied
      whether tumor growth in vivo was affected by the administration of propofol.
      Tumor growth was significantly suppressed in mice that were given propofol,
      compared with tumor growth in mice given saline. Therefore, it is concluded that
      propofol may have a beneficial effect on antitumor immunity in mice.

PMID- 18075860
TI  - Expression of Co-stimulatory molecules on langerhans cells in lesional epidermis
      of human atopic dermatitis.
AB  - Langerhans cells (LC) are immature dendritic cells (DC) present in the skin
      epithelium. To understand the molecular and cellular mechanisms governing the
      inflammatory reaction in atopic dermatitis (AD), the expression of the LC
      specific marker CD1a, a member of major histocompatibility (MHC)-like
      glycoproteins, and the co-stimulatory molecules CD80 and CD86, expressed on
      functionally mature dendritic cells, were counted in lesional biopsies and normal
      epidermis by an immunohistochemical method. CD1a specific staining was observed
      in both normal and AD lesion specimens. CD80 and CD86 positive cells with
      morphological characteristics of the LC were found in lesional AD epidermis,
      suggesting a high level of functional maturity of these cells and their
      involvement in chronic inflammatory disease.

PMID- 18075861
TI  - The Structure of the 18S rRNA, a molecule that might be evolutionarily related to
      some receptors of innate immunity.
AB  - Comparisons between the sequences of insect and vertebrate 18S rRNAs and the
      sequences of mammalian formyl peptide and some vertebrate chemokine receptor
      mRNAs demonstrated non-random structural similarities between these two groups of
      RNAs. It has been proposed that sections of the more ancient and conserved rRNA
      genes could have participated in the building of these more recent genes involved
      in immune responses. Here we analyze the sequence architecture of the 18S rRNA in
      insects (Drosophila simulans) and vertebrates (man), in terms of similarities
      between selected segments within the individual molecules. The insect and
      vertebrate 18S rRNAs are basically similar, but show specific
      insertions/deletions and base changes. In spite of these differences, in both
      sequences a significantly higher-than-expected (by random occurrence) number of 7
      or-more-base oligonucleotide repeats was observed between segments roughly
      corresponding to nt 350-1050 and nt 1150-1850, with mutual between-repeats
      distances comprised in the range 700-900 nt. Based on this result we performed a
      multialignment of segments 317-1035 of Drosophila, 360-1005 of man, 1096-1864 of
      Drosophila, and 1066-1736 of man, the first two segments covering the region of
      first occurrence of the repeats and the last two the region of recurrences. At
      both ends of these segments the four sequences could be aligned with relatively
      minor gaps and the number of base identities in all four sequences was
      significantly higher than expected by random coincidences. These results support
      the hypothesis that an ancestral gene structure, composed of a chain of about 700
      nt, duplicated to form a two-unit tandem repeat which still represents the most
      substantial part of the 18S rRNA molecule in extant insects and vertebrates.

PMID- 18075862
TI  - Evaluation of the immunomodulatory activities of royal jelly components in vitro.
AB  - In this work the effect of different components isolated from royal jelly (RJ)
      was studied using an in vitro rat T-cell proliferation assay. We found that lower
      concentrations of MEL 174 (final water extract of RJ) and MEL 147 (3-10
      dihydroxydecanoic acid) stimulated T-cell proliferation, triggered by
      concanavalin A (Con-A) and the process was followed by an increase in the
      production of interleukin-2 (IL-2). Higher concentrations of MEL 174, MEL 247
      (dry powder of RJ) and MEL 138 (trans-10-hydroxydec-2-enoic acid) inhibited T
      cell proliferation. The inhibition of T-cell proliferation in the presence of MEL
      174 was followed by a decrease in IL-2 production, which was partly abrogated by
      exogenous IL-2, a decrease in nitric oxide (NO) production and increased
      apoptosis. In conclusion, our results showed the complexity of biological
      activity of RJ and suggest that its water extract possesses the most potent
      immunomodulatory activity in vitro.

PMID- 18075863
TI  - Selective effect of mercury on Th2-type cytokine production in humans.
AB  - Mercury induces autoimmune disease and increases IL-4 production and IgE levels
      in certain rodent strains. The object of this study was to determine if mercury
      was capable of inducing Th2 cytokine production in human leucocytes. Human
      peripheral blood mononuclear cells (PBMC) were incubated with PMA/ionomycin or
      Con A in the presence or absence of methyl mercury (CH(3)Hg) or mercuric chloride
      (HgCl(2)). IL-4 and gamma-IFN were measured by ELISA. RESULTS: IL-4 production
      significantly increased at low concentrations of CH(3)Hg (0.5 uM, p < 0.01),
      while gamma-IFN production was suppressed starting at CH(3)Hg 2 uM (p = 0.004).
      Inorganic mercury (HgCl(2)) increased IL-4 only at concentrations 10-20 times
      higher than CH(3)Hg. These findings suggest a mechanism by which mercury could
      trigger or potentiate TH2 cytokine production in humans.

PMID- 18075864
TI  - The immunomodulatory activity of C3 binding glycoprotein (C3bgp) is mediated by
      the complement receptor type III and mitogen-activated protein kinase signal
      transduction pathways.
AB  - C3 binding glycoprotein (C3bgp) is immunomodulating molecule isolated from the
      plant Cuscuta europea. When neutrophils were incubated with C3bgp the subsequent
      binding of anti-CD11b mAb became significantly higher. C3bgp induced moderate TNF
      alpha production in human PBMC and primary monocytes. This production was
      significantly inhibited by the specific inhibitors of JNK and p38 MAPKs. The
      inhibition of JNK reduced PBMC viability. We concluded that: (i) C3bgp utilized
      CD11b polypeptide chain of CR3 and mediated a part of its immunomodulatory
      properties by activation of JNK and p38 and (ii) PBMC viability at in vitro
      conditions depends of JNK signal transduction pathway activation.

PMID- 18075865
TI  - Obtainment of polyclonal antibodies to clenbuterol with the use of colloidal
      gold.
AB  - The effectiveness of an in vivo synthesis of antibodies to clenbuterol with the
      use of gold nanoparticles as a carrier was evaluated. For comparison, conjugates
      of clenbuterol with bovine serum albumin were used in immunization. The serum
      titer was determined by an ELISA. The antibodies were tested by an immunodot
      assay with immunogold markers. With both techniques we obtained specific and
      relatively high-titer antibodies to clenbuterol. It was found that the antibodies
      obtained with the use of gold nanoparticles were not inferior in titer to those
      obtained to the conjugates of clenbuterol with the protein but surpassed them in
      specificity.

PMID- 18075866
TI  - Effect of Punarnavine, an alkaloid from Boerhaavia diffusa, on cell-mediated
      immune responses and TIMP-1 in B16F-10 metastatic melanoma-bearing mice.
AB  - Effect of Punarnavine on the cell-mediated immune (CMI) response in metastatic
      condition was studied using C57BL/6 mice model. Administration of Punarnavine
      enhanced Natural Killer (NK) cell activity, antibody-dependent cellular
      cytotoxicity (ADCC) and antibody-dependent complement mediated cytotoxicity (ACC)
      and the activity was observed in treated group much earlier compared to the
      metastatic tumor-bearing control. Production of cytokines such as IL-2 and IFN
      gamma were significantly enhanced by the administration of Punarnavine compared
      to the untreated metastatic tumor-bearing control. Peaks of pro-inflammatory
      cytokines such as IL-1beta, IL-6 and TNF-alpha were significantly lowered by
      Punarnavine administration compared to metastatic control. The level and
      expression of TIMP-1 was also enhanced by the administration of Punarnavine
      compared to metastatic tumor bearing control. These results indicate Punarnavine
      could enhance the immune response against metastatic progression of B16F-10
      melanoma cells in mice.

PMID- 18075867
TI  - Immunomodulatory effects of erythromycin and its derivatives on human T
      lymphocyte in vitro.
AB  - To elucidate the immunomodulatory mechanisms of macrolides, we investigated here
      the effects of erythromycin (EM) and its derivatives, 1 and 2, which show no
      antibacterial activity, on the proliferation and the activation of the
      transcription factor nuclear factor-kappaB (NF-kappaB) in Jurkat T cells. MTT
      assay revealed that EM, 1 and 2 could inhibit T lymphocyte proliferation
      markedly. Flow cytometry and TUNEL analysis showed EM (30 microg/mL-100
      microg/mL) and 1 (3 microg/mL-30 microg/mL) could induce T lymphocyte apoptosis,
      2 (3 microg/mL-30 microg/mL) induced a cell cycle arrest in G(2)/M. RT-PCR and
      Western blotting analysis conformed that EM and its two derivatives could inhibit
      the expressions of NF-kappaB mRNA and protein. Taken together, these data suggest
      EM and its derivatives, 1 and 2, have immunomodulatory effect, presumably via an
      interaction with the NF-kappaB expression, inhibiting the proliferation of T
      lymphocyte, implicating an approach for the development of new drugs for treating
      inflammatory diseases.

PMID- 18075868
TI  - 17beta-estradiol enhances contact hypersensitivity in a hair cycle-dependent
      manner and retards thymic atrophy with age.
AB  - The effect of 17beta-estradiol (E2) on murine contact hypersensitivity (CHS),
      thymic atrophy, and hair-cycle change related to growth was investigated. Female
      mice were ovariectomized. E2 (3.2 microg) was injected subcutaneously along with
      the sensitizer 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (OXA), and a
      hypersensitive reaction was elicited with OXA on the ear in mice of various ages.
      E2 enhanced allergy only in 3- and 7-week-old mice, just prior to hair regrowth.
      Age-related thymus atrophy was repressed in the E2-treated mice compared with the
      control mice. E2 alone did not cause thymus involution, but it did inhibit thymus
      involution and regeneration after CHS.

PMID- 18075869
TI  - Early effects triggered by Larrea divaricata Cav. on murine macrophages at
      apoptotic concentrations.
AB  - Decoction and infusion of Larrea divaricata were tested at apoptotic
      concentrations (1 and 4 mg/ml) on peritoneal murine macrophages. Consistent
      changes were observed after incubation with 4 mg/ml decoction. Phagocytosis of
      zymosan, lysosomal enzyme activity, nitric oxide production, TNF-alpha release,
      and expression of CD14, TLR4, and CR3 increased significantly. Decoction at 1 and
      4 mg/ml increased the binding of LPS-FITC. Apoptosis triggered by L. divaricata
      decoction is consequence of cell activation. The effects are independent of
      nordihydroguaiaretic acid. This "activation and death" could be the mechanism of
      L. divaricata to exert the antituberculosis effect known in folk medicine.

PMID- 18075870
TI  - Analysis and testing of a hidden stepladder hazard - excessive twist flexibility.
AB  - Accidental falls from stepladders are responsible for tens of thousands of
      injuries in the US each year. This paper augues recent research concerning
      excessive stepladder twist flexibility, which can lead to ladder falls. Such
      falls can easily occur when only three of a ladder's four legs are in contact
      with the ground and an unknowing climber shifts his weight, causing the ladder's
      raised leg to move suddenly downward and the climber to lose his balance. The
      static and dynamic test and analysis results presented show a major cause of this
      hazard, its effect on climbers and the influence of ladder design on the
      likelihood of its occurrence. The inadequacy of existing stepladder safety
      standards to protect against such accidents is noted and a call for a new testing
      standard is outlined. It would be prudent to develop and implement a new racking
      test and stiffer ladder twist requirements to reduce the likelihood of
      inadvertent ladder racking.

PMID- 18075871
TI  - Testing impact attenuation on California playground surfaces made of recycled
      tires.
AB  - This study was conducted to determine whether rubberized playground surfaces made
      of recycled tires comply with state-mandated standards for impact attenuation
      (measured with an accelerometer), and whether their properties change in response
      to temperature or time. The Head Impact Criterion (HIC) standard of 1000 was
      found to be a more sensitive indicator of compliance than the G(max) standard of
      200(g). Of 32 playgrounds tested, 22 (69 percent) failed the HIC standard. As the
      heights of playground structures increased, so did the likelihood that the
      rubberized surface below would fail the HIC standard. Rubberized surfaces gave
      stable readings for the first three months following installation, and higher
      values in response to increasing surface temperature. An excessively high
      percentage of playground surfaces made of recycled tires failed the state
      mandated standards designed to prevent serious head injury from falls. Future
      failures might be prevented by requiring installers to perform post-installation
      testing to verify compliance.

PMID- 18075872
TI  - The pattern of deaths in road traffic crashes in Sindh, Pakistan.
AB  - The objectives of this study were to examine the pattern and magnitude of deaths
      in road traffic crashes (RTCs) in Sindh province of Pakistan. This cross
      sectional study used data obtained from government documents and content analysis
      of daily newspapers' reports on incidents of deaths in RTCs. Results showed that
      the total annual number of RTCs, fatal RTCs and deaths in RTCs were 2272 (+/
      293), 1104 (+/-89) and 1321 (+/-136) respectively. On average, there were four
      deaths per day in RTCs. The victims were 85% male and the majority were between
      15 and 49 years of age. Pedestrians, passengers, motorcyclists and drivers were
      most commonly the victims. Deaths in RTCs were double in rural areas compared to
      urban areas. The most common causes of fatal RTCs were by being hit by a vehicle,
      breakdown and collision of motor vehicles and speeding. The frequent involvement
      of the men of working age in RTCs may have serious social and economic
      implications; therefore, the prevention of RTCs, as far as possible, is
      imperative.

PMID- 18075873
TI  - Uncovering evidence on community-based injury prevention: A review of programme
      effectiveness and factors influencing effectiveness.
AB  - This study examines systematic reviews of community-based injury prevention
      programmes to obtain an overview of the evidence base on the effectiveness of
      these programmes and to analyse how effectiveness is measured and the extent to
      which factors contributing to achieving programme effectiveness are examined in
      these reviews. Thirteen systematic reviews were found, encompassing a total of
      121 programmes. The results reinforced the well-documented point that the
      evidence regarding the effectiveness of community-based injury prevention
      programmes is inconsistent. Some of the programmes targeting specific injury
      categories, e.g. specific injury types and/or age groups, were successful, whilst
      more broadly targeted programmes demonstrated less convincing results.
      Effectiveness was predominantly measured as injury rate reductions. Only one of
      the reviews identified contextual factors that could have impacted on programme
      effectiveness. To advance the field, researchers and systematic reviews need to
      include evidence on factors that may explain how the effects were achieved.

PMID- 18075874
TI  - Safety programmes in the Egyptian construction industry.
AB  - This study is aimed at exploring the nature of the safety programmes applied by
      large-size contractors operating in Egypt. Results revealed that safety
      programmes applied by those contractors were less formal than the programmes
      applied by their American counterparts. Only three contractors out of the
      surveyed sample had accident records broken down by projects, provided workers
      with formal safety orientation, and trained safety personnel on first-aid. The
      study recommended that reforms to the scheme of the employers' contribution to
      social insurance are necessary. This is meant to serve as a strong incentive for
      safety management.

PMID- 18075875
TI  - The epidemiology of head, face and eye injuries to female lacrosse players in
      Australia.

PMID- 18075876
TI  - Childhood injuries in Greek school environment.

PMID- 18075877
TI  - Describing the epidemiology and associated age, gender and handicap comparisons
      of golfing injuries.

PMID- 18075878
TI  - Intrinsic risk factors for falls by community-based seniors: implications for
      prevention.

PMID- 18075879
TI  - The role of public health in injury prevention in the WHO European region.

PMID- 18075880
TI  - Estimating nurses' exposures to ionizing radiation: the elusive gold standard.
AB  - This study assessed ionizing radiation exposure in 58,125 registered nurses in
      British Columbia, Canada, for a cohort study of cancer morbidity and mortality.
      Two methods were used: (1) a survey of nurses in more than 100 acute care
      hospitals and health care centers; (2) and monitoring data reported to the
      National Dose Registry of Health Canada, considered the gold standard. The mean
      exposure of cohort nurses monitored during the study period from 1974 to 2000 was
      0.27 milliSieverts (7028 person-years of monitoring). Of 609,809 person-years in
      the cohort, 554,595 (90.9%) were identified as unexposed by both exposure
      assessment methods. Despite crude agreement of 91% between the methods, weighted
      kappa for agreement beyond chance was only 0.045, and the sensitivity of the
      survey method to capture National Dose Registry monitored person-years was only
      0.085 (specificity = 0.97). The survey missed exposures outside the acute care
      setting. The National Dose Registry also missed potential exposures, especially
      among hospital emergency department and pediatric staff nurses. It was unlikely
      that either method estimated nurses' true exposures to ionizing radiation with
      good sensitivity and specificity. The difficulty in exposure assessment likely
      arises because fewer than 10% of registered nurses are exposed to ionizing
      radiation, yet the settings in which they are exposed vary tremendously. This
      means that careful hazard assessment is required to ensure that monitoring is
      complete where exposures are probable, without incurring the excess costs and
      lack of specificity of including the unexposed.

PMID- 18075881
TI  - Verifying interpretive criteria for bioaerosol data using (bootstrap) Monte Carlo
      techniques.
AB  - A number of interpretive descriptors have been proposed for bioaerosol data due
      to the lack of health-based numerical standards, but very few have been verified
      as to their ability to describe a suspect indoor environment. Culturable and
      nonculturable (spore trap) sampling using the bootstrap version of Monte Carlo
      simulation (BMC) at several sites during 2003-2006 served as a source of indoor
      and outdoor data to test various criteria with regard to their variability in
      characterizing an indoor or outdoor environment. The purpose was to gain some
      insight for the reliability of some of the interpretive criteria in use as well
      as to demonstrate the utility of BMC methods as a generalized technique for
      validation of various interpretive criteria for bioaerosols. The ratio of
      nonphylloplane (NP) fungi (total of Aspergillus and Penicillium) to phylloplane
      (P) fungi (total of Cladosporium, Alternaria, and Epicoccum), or NP/P, is a
      descriptor that has been used to identify "dominance" of nonphylloplane fungi
      (NP/P > 1.0), assumed to be indicative of a problematic indoor environment.
      However, BMC analysis of spore trap and culturable bioaerosol data using the NP/P
      ratio identified frequent dominance by nonphylloplane fungi in outdoor air.
      Similarly, the NP/P descriptor indicated dominance of nonphylloplane fungi in
      buildings with visible mold growth and/or known water intrusion with a frequency
      often in the range of 0.5 Fixed numerical criteria for spore trap data of 900 and
      1300 spores/m(3) for total spores and 750 Aspergillus/Penicillium spores/m(3)
      exhibited similar variability, as did ratios of nonphylloplane to total fungi,
      phylloplane to total fungi, and indoor/outdoor ratios for total fungal spores.
      Analysis of bioaerosol data by BMC indicates that numerical levels or descriptors
      based on dominance of certain fungi are unreliable as criteria for characterizing
      a given environment. The utility of BMC analysis lies in its generalized
      application to test mathematically the validity of any given descriptor or
      criterion for bioaerosols, which can be an important tool in quantifying the
      uncertainty in interpreting bioaerosol data.

PMID- 18075882
TI  - Cleaning efficacy of high-efficiency particulate air-filtered vacuuming and "dry
      steam" cleaning on carpet.
AB  - Previous studies for lead exposure reduction have indicated the difficulty in
      reducing surface contamination of carpets with the use of regular vacuum
      cleaners. To find a solution, a household vacuum cleaner equipped with a high
      efficiency particulate air (HEPA) filter and a dust finder indicator, and a "dry
      steam" cleaner previously reported effective in reducing dust mite allergens in
      carpets and mattresses were tested for effectiveness in reducing lead dust in
      carpets. Fifty homes of lead-exposed children were tested in New Jersey. A
      selected carpet in the living area of each home was tested with two
      interventions: half was cleaned by HEPA vacuuming twice (VAC-VAC) and the other
      half by dry steaming between the two HEPA vacuumings (VAC-DSC-VAC). Wipe and
      vacuum samples, representing surface dust and total dust collections,
      respectively, were taken before and after cleaning. The wipe and vacuum sample
      data indicated that both cleaning methods substantially reduced dust lead levels
      (p < 0.001). The mean percent reductions in lead loading were approximately 29%
      and 40% for the VAC-VAC and VAC-DSC-VAC interventions, respectively. The
      difference between the two postcleaning levels was statistically significant by
      wipe sampling (p = 0.038) but was marginally insignificant by vacuum sampling (p
      = 0.072). A subset of sample data collected before repeat vacuuming (VAC-DSC)
      suggested that repeat vacuuming after dry steam cleaning is unnecessary. In
      summary, slow and steady HEPA vacuuming with the help of a dust finder indicator
      reduces surface and overall lead dust in carpets, and dry steam cleaning further
      reduces surface lead contamination as compared with HEPA vacuuming alone.

PMID- 18075883
TI  - Liposomes from a new chiral cationic lipid based on iridoidic template.
AB  - A new cationic polyhydroxylated lipid, characterized by a chiral template, was
      synthesized. It comes from an iridoid glucoside, as polyhydroxylated moiety. This
      lipid affords liposomes using cholesterol-like co-lipid. The liposomes had a
      spheroidal shape with a small size distribution.

PMID- 18075884
TI  - In vitro antitumor activity of triterpenes from Ceriops tagal.
AB  - The embryo of Ceriops tagal was extracted with 95% ethanol at room temperature,
      and four triterpenes (1-4) were separated from this extract. For the first time
      these triterpenes were the separated from this plant. Compounds (1-4) were tested
      in vitro for antitumor activity against three cell lines (human liver cancer cell
      (H-7402), human B-lymphoblastoid cell (Raji), and human cervical carcinoma cell
      (Hela)). Compounds 1 and 3 were effective to inhibit cell proliferation and
      growth of H-7402 and Hela, the IC(50) of them on H-7402 were 14.42 microg mL(-1)
      and 9.97 microg mL(-1), and the IC(50) of them on Hela were 11.84 microg mL(-1)
      and 11.32 microg mL(-1). All compounds 1-4 were not effective to inhibit cell
      proliferation and growth of Raji. The effects of compound 4 on inhibiting
      proliferation and growth of these three cancer cells was also not obvious.

PMID- 18075885
TI  - Mechanism of anti-inflammatory action of liquorice extract and glycyrrhizin.
AB  - The antiradical activity, protective effect against lipid peroxidation of
      liposomal membrane, and inhibitory effect on whole blood reactive oxygen species
      (ROS) liberation of Glycyrrhiza glabra crude extract and glycyrrhizin, its major
      compound, were assessed. The liquorice extract showed significant activity in all
      the three assay systems used in a dose dependent manner. It displayed remarkable
      reactivity with free stable 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical,
      inhibitory efficacy in peroxidatively damaged unilamellar dioleoyl
      phosphatidylcholine (DOPC) liposomes, and inhibition of ROS chemiluminescence,
      generated by whole blood, induced by both receptor-bypassing stimuli (PMA) and
      receptor operating stimuli (Opz) in the ranking order of stimuli PMA> Opz. These
      activities may be attributed to phenolic antioxidants involving isoflavan
      derivatives, coumarins and chalcones. Nonetheless, triterpene saponin
      glycyrrhizin exhibited no efficacy in the system of DPPH reaction and
      peroxidation of liposomal membrane, and negligible inhibition of
      chemiluminescence generated by inflammatory cells. These results indicate that
      the mechanism of anti-inflammatory effect of glycyrrhizin most probably does not
      involve ROS and this major constituent is not responsible for the inhibition
      effects of liquorice extract on neutrophil functions.

PMID- 18075886
TI  - First isolation of sesquiterpenes and flavonoids from Zingiber spectabile and
      identification of zerumbone as the major cell growth inhibitory component.
AB  - Nine sesquiterpenes and eight flavonoids were isolated from Zingiber spectabile
      for the first time. Structures were determined by spectroscopic methods. The
      major compound zerumbone (1) was found to be the most active (IC(50) 13 microg
      mL(-1)) in cell growth inhibitory assay against colon carcinoma SW480 cells.

PMID- 18075887
TI  - CPT accumulation in the fruit and during early phases of plant development in
      Camptotheca acuminata Decaisne (Nyssaceae).
AB  - We describe the dynamics of camptothecin (CPT) accumulation during the early
      phases of plant development in Camptotheca acuminata. TLC and HPLC analyses were
      performed on the entire mature fruit and all of its parts and on the organs of
      seedlings in different developmental stages. In the mature fruit, the CPT content
      was relatively high (2.83 mg g(-1) DW); it was accumulated especially in the
      endosperm (1.82 mg g(-1) DW) and embryo (1.10 mg g(-1) DW). Regarding seedlings,
      CPT was present in all of the organs, at all developmental stages. In the
      cotyledons, content was greatest in the early developmental stages (4.23 mg g(-1)
      DW) and drastically decreased once the organ reached maturity (0.34 mg g(-1) DW).
      A similar trend was observed for the true leaves. The results suggest that CPT is
      translocated from the organs at an advanced developmental stage to those at an
      early stage.

PMID- 18075888
TI  - A myxobacterium strain Sorangium cellulosum AHB125 producing epothilone B and
      other anticancer substances.
AB  - A myxobacterium strain AHB125 belonging to genus Sorangium cellulosum was
      isolated from Anhui area in China and identified with morphological analysis by
      electron microscopy and phase contrast microscope according to Bergey's manual of
      systematic bacteriology (8th Ed.). Its high-antitumor bioactivity metabolites was
      evaluated by bioassay-directed screening technique with B16 tumor cell line etc.
      Research results showed that it exhibited not only strong antitumor ability
      bioactivities and broad-spectrum antitumor abilities to B16, Bel7402, H446,
      SGC7901 cell lines, but also has selectivity and pertinence to B16 and SGC7901
      cell lines. The compound was confirmed as epothilone B by HPLC and LC/MS
      analysis, compared to the epothilone B standard sample. Bioassay indicated that
      there were other high-bioactive substances in the metabolites.

PMID- 18075889
TI  - Antistress and antiallergic effects of Ficus bengalensis bark in asthma.
AB  - Various extracts of Ficus bengalensis bark was screened for it's antiallergic and
      antistress potential in asthma by milk-induced leucocytosis and milk-induced
      eosinophilia. Aqueous, ethanol, and ethyl acetate extracts showed significant
      decrease in leucocytes and eosinophils in the order given while petroleum ether
      and chloroform extracts were inactive. This shows the application of polar
      constituents of F. bengalensis bark as antistress and antiallergic agents in
      asthma.

PMID- 18075890
TI  - Study on the structure-activity relationships of phoxalone and induction of
      apoptosis in H446 tumor cells.
AB  - A novel macrolide with dioxa and double ring pentadecanone, named as phoxalone,
      isolated from the culture broth of a myxobacterium Sorangium cellulosum WXNXJ-C,
      was well investigated. The chemical structure of Phoxalone was elucidated by
      spectroscopic analysis including UV, IR, (1)H NMR, MALDI-TOF-MS, and LC/MS
      spectra. The results of cytotoxic bioactivities on human non-small lung cancer
      H446, in vitro, showed that not only did phoxalone express higher antitumor
      bioactivity than many antitumor drugs, but it also displayed less cytotoxicity to
      normal human liver L02 cell lines (IC(50), 286 microg mL(-1)). Further cytotoxic
      bioactivity study indicated that phoxalone could induce H446 cell line apoptosis
      in vitro. More investigation results of flow-cytometric analysis suggested that
      phoxalone arrested the mitosis of H446 cell line at G2/M phase. Hence, phoxalone
      and its derivatives or analogs would reveal huge research value and fascinating
      foreground.

PMID- 18075891
TI  - Weed growth inhibitors from Aspergillus fischeri TISTR 3272.
AB  - Chloroform and ethyl acetate extracts of Aspergillus fischeri TISTR 3272 showed
      good growth inhibitory activity on Mimosa pigra and Echinochloa crus-galli.
      Bioassay-directed fractionation of the active extracts led to the isolation of
      five known compounds, (+)-terrein (1), (-)-6-hydroxymellein (2), two
      diketopiperazines (cyclo-(S-Pro-S-Leu) (3) and cyclo-(S-Pro-S-Val) (4)) and
      butyrolactone I (5). Compounds 2-5 were reported for the first time in this
      fungus. Their structural determinations were based on analyses of spectroscopic
      data and their weed growth inhibitory effects were assessed.

PMID- 18075892
TI  - Chemical composition of the essential oil of Thalectrum minus L. of Iran.
AB  - The volatile constituents of the essential oil of Thalictrum minus L. growing
      wild in Kurdistan-Iran were investigated by GC and GC / MS technique. Twelve
      compounds, representing 100% of the total oil were identified. The main
      components were: Thymol (66.63%), para-Cymene (13.05%), gamma-Terpinene (7.32%),
      Carvacrol (3.70%), 1,8-Cineole (2.02%).

PMID- 18075894
TI  - Phytochemical analysis of the essential oil of Thymus serpyllum L. growing wild
      in Estonia.
AB  - Variations in the essential oil composition of Thymus serpyllum L., growing wild
      in Estonia (33 samples) and in some other countries (Russia, Latvia and Armenia,
      seven samples) were determined. The oil were obtained from Estonia (46 samples)
      in yields 0.6-4.4 and 1.9-8.2 mL kg(-1) in other countries. The T. serpyllum herb
      grown in Estonia usually did not confirmed to the EP standard in the aspect of
      the essential oil contents (3.0 mL kg(-1)). Variations in the essential oil
      composition of wild thyme were studied using capillary gas chromatographic
      methods. A total of 94 components were identified. Thymol and carvacrol,
      mentioned in literature as principial components, are not the main components of
      the essential oil of wild thyme growing in Estonia. (E)-nerolidol, caryophyllene
      oxide, myrcene and borneol chemotypes of wild thyme drug are distinguishable. The
      chemical composition of samples from Russia, Latvia and Armenia is very variable.

PMID- 18075893
TI  - Effects on free radicals and inhibition of alpha-amylase of Cardamine battagliae
      (Cruciferae), an apoendemic Calabrian (southern Italy) plant.
AB  - The present study showed for the first time the biological properties of
      different fractions from Cardamine battagliae Cesca & Peruzzi, an apoendemic
      Calabrian (southern Italy) plant that belongs to the Cruciferae family. The
      antioxidant activities of the different fractions of C. battagliae were carried
      out using two different in vitro assays (beta-carotene bleaching test and lipid
      peroxidation of liposomes assay) while radical scavenging activity was carried
      out using DPPH test. AcOEt fraction showed the highest activity on DPPH
      inhibition (IC50 of 0.162 mg mL(-1)) while dichloromethane fraction showed the
      highest activity on beta-carotene bleaching (IC(50) of 0.004 mg mL(-1)). The
      assay for alpha-amylase inhibition showed that n-hexane fraction showed the
      highest activity with an IC50 of 0.055 mg mL(-1).

PMID- 18075896
TI  - Characterization and crystal structure of 2R-(-)-6-hydroxytremetone from
      Xenophyllum poposum (Phil.) V.A. Funk.
AB  - 2R-(-)-6-Hydroxytremetone (C13H14O3) is a bioactive metabolite isolated from
      Xenophyllum poposum (Phil.) V.A. Funk. (ex. Werneria poposa Phil.), a member of
      the Asteraceae. Various pharmacological properties attributed by popular medicine
      to benzofurane derivatives prompted their physical and chemical characterization.
      The obtained substance was characterized by melting point, optic rotation,
      ultraviolet spectrum, 1HRMN, 13CRMN, infrared spectroscopy, and thermo-analytical
      techniques. The molecular structure of 2R-(-)-6-hydroxytremetone was determined
      by single crystal X-rays diffraction methods. The substance crystallizes in the
      monoclinic space group P2(1) with a = 8.767(2) A, b = 5.423(1) A, c = 24.301(4)
      A, beta = 90.52(2) degrees , and two independent but very similar molecules of
      the same handedness per asymmetric unit (Z = 4). Both molecules have the phenyl
      ring and its attached oxydryl and methyl ketone groups nearly co-planar to one
      another and are stabilized by a strong OH ... Oketone intra-molecular bond
      (Ohydroxyl ... Oketone distances of 2.529 and 2.536 A; O-H ... Oketone angles of
      146.4 and 143.9 degrees , respectively).

PMID- 18075895
TI  - Carroll rearrangement to construct the norneolignan skeleton.
AB  - A three-step synthesis of the norneolignan skeleton involving the Carroll
      rearrangement as the key step has been developed and used for synthesis of the
      norneolignan skeleton, 1,3-diphenylpenta-1,4-diene and hinokiresinol.

PMID- 18075897
TI  - Biological screening of some Turkish medicinal plant extracts for antimicrobial
      and toxicity activities.
AB  - Screening of antibacterial activity and toxicity of 22 aqueous plant extracts
      from 17 Turkish plants was conducted. Antibacterial activity was performed with
      six bacteria including Escherichia coli, Pseudomonas aeruginosa, Klebsiella
      pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Staphylococcus
      epidermidis. Extracts of Tussilago farfara leaves, Helichyrsum plicatum flowers,
      Solanum dulcamara aerial parts and Urtica dioica leaves gave the best inhibitory
      activity against S. pyogenes, S. aureus and S. epidermidis. Of the 22 plant
      extracts, 20 extracts displayed toxicity (LC50 was <1000 mg L(-1)) in the brine
      shrimp bioassay. For radish seed bioassay, two different determinations (root
      length and seed germination) were performed with a comparison between two
      concentrations (50,000 mg L(-1) and 10,000 mg L(-1)). At low concentration
      (10,000 mg L(-1)), S. dulcamara aerial parts and Primula vulgaris leaf extracts
      were observed to inhibit the root length more than the other plant extracts.
      Also, the most inhibitive plant extract for seed germination was obtained with S.
      dulcamara aerial parts.

PMID- 18075898
TI  - Steroidal glycoalkaloids from the berries of Solanum distichum.
AB  - Two steroidal glycoalkaloids, Solanidine 3-O-[alpha-L-rhamnopyranosyl-(1'' --> 4)
      [alpha-L-rhamnopyranosyl-(1' --> 2)]-beta-D-glucopyranoside] (1) and Solanidine 3
      O-[alpha-L-rhamnopyranosyl-(1'' --> 4)-beta-D-glucopyranoside] (2) commonly known
      as alpha-chanonine and beta 2-chanonine, were isolated from the berries of
      Solanum distichum. The structures of the isolated compounds were studied by 1D
      and 2D NMR techniques and FAB MS analysis. The 13C NMR signal assignments and
      direct elucidation of the glycoside linkages were established. Glycoalkaloids
      level in the dried berries, determined by a simple colorimetric method, was found
      to be 5.08 +/- 0.18 g%.

PMID- 18075899
TI  - Antifouling and antibacterial compounds from the gorgonians Subergorgia suberosa
      and Scripearia gracillis.
AB  - In this study, we investigated the potential antilarval and antibacterial
      activity of secondary metabolites of the gorgonians Subergorgia suberosa and
      Scripearia gracillis from the South China Sea. Fresh specimens of these two
      gorgonian corals were collected from a shallow reef in Sanya Bay of Hainan Island
      and extracted with different solvents. Antilarval activity of the chemical
      extracts and pure compounds was evaluated in settlement inhibition assays with
      laboratory-reared Balanus amphitrite and Bugula neritina larvae, while
      antibacterial activity was assessed with disc diffusion bioassay on growth
      inhibition of 15 marine bacterial species. Using bioassay-guided procedures, we
      purified and identified nine compounds. The most potent metabolites produced by
      these gorgonian corals were subergorgic acid and pregn-4-ene-3, 20-dione
      extracted from S. suberosa. Our results show that the gorgonian coral S. suberosa
      and S. gracillis can produce potent anti-fouling compounds that deserve further
      exploration.

PMID- 18075900
TI  - Terpenoids and phenolics from Plectranthus strigosus, bioactivity screening.
AB  - Further studies on Plectranthus sp. (Lamiaceae) led to the isolation of terpenes
      and phenol esters from Plectranthus strigosus Benth. ent-16-Kauren-19-ol (1), ent
      16-kauren-19-oic acid (2), xylopic acid (3), xylopinic acid (4), hinokiol (5), 4
      beta,6 beta-dihydroxy-1 alpha,5 beta(H)-guai-9-ene (6) 4 beta,6 beta-dihydroxy-1
      alpha,5 beta(H)-guai-10(14)-ene (7), mixtures of hexacosan-1,26-diol and
      octacosan-1,28-diol ferulate diesters (8), of esters from ferulic acid and fatty
      alcohols (9) and of esters from fatty acids and 2-(4-hydroxyphenyl)-ethanol (10)
      were for the first time isolated from this genus. Supplementary spectral data for
      3,8 and parvifloron D (11) metabolites are also presented. A bioactivity study
      revealed herpetic inhibitory properties for (1) and (2), and antioxidant ability
      for (5) and (8) phenolic constituents.

PMID- 18075902
TI  - Extraction of flavonoids from Rhodiola sachlinesis A. Bor by UPE and the
      antioxidant activity of its extract.
AB  - Rhodiola sachlinesis, A. Bor is one of the most popular traditional Chinese
      medicines and has been proved to have many effective compounds, such as
      flavonoids, anthraglycosides, essential oil with cinnamic aldehyde and citral and
      organic acids. In this article, a new method of ultrahigh pressure extraction
      (UPE) was used to extract flavonoids from R. sachlinesis. Uniform Design was
      employed to get the optimum extraction conditions. The optimum UPE conditions
      were as follows: pressure was 500 MPa; ethanol concentration was 40%;
      solid/liquid ratio (g mL(-1)) was 1 : 70. The optimum extraction yield of
      flavonoids was 52.33 mg g(-1). The antioxidant activity of the crude extract was
      tested with DPPH assay. It showed a higher activity, compared with tertiary
      butyhydroquinone (TBHQ) at the same concentration (1 mg mL(-1)).

PMID- 18075904
TI  - Doppler insonation of vertebral artery blood flow changes associated with
      cervical spine rotation: Implications for manual therapists.
AB  - The controversy related to changes in vertebral artery (VA) blood flow associated
      with rotation of the cervical spine and the implications for professional
      practice is still of concern to manual therapists. The aim of this review of the
      literature is, first, to assess current evidence of altered VA blood flow
      following cervical spine rotation in persons with and without signs and symptoms
      of vertebrobasilar ischemia/insufficiency (VBI). Second, any reported, related
      alterations in blood flow that may have consequences for the individual will be
      discussed to assist manual therapists in pretreatment risk assessment of
      patients. The most commonly used noninvasive, in vivo technique for measuring
      blood flow is Doppler ultrasonography. Of the 88 relevant papers retrieved by a
      systematic literature search covering the past 50 years, 20 studies reported
      measurement of VA blood flow related to cervical spine rotation. A critical
      analysis of these reports revealed that there is no standardization of methods
      used (heterogeneous samples, small sample sizes, various measurement positions
      and instruments, and different parts of the VA measured); no consensus of
      findings (no change, and a significant reduction in contralateral VA blood flow,
      with or without VBI); and no correlations found between rotation, blood flow, and
      VBI. Nevertheless, this review is of value in increasing our knowledge of the
      possible mechanisms and consequences of repeated minor arterial trauma and of
      blood flow changes related to rotational movements used in cervical manual
      therapy. It highlights, too, the need for caution in the interpretation of
      pretreatment risk assessment outcome measures.

PMID- 18075905
TI  - Does stabilization of the tibiofemoral joint affect passive prone hip rotation
      range of motion measures in unimpaired individuals? A preliminary report.
AB  - Use of the tibia as a lever to produce hip rotation for the purpose of measuring
      passive hip rotation range of motion (ROM) could result in inaccurate values if
      motion is allowed at the tibiofemoral joint (TFJ). The purpose of this study was
      to examine the effect of stabilizing the TFJ during measurement of prone hip
      rotation ROM in men and women. Passive hip rotation was measured in 20 unimpaired
      subjects (M = 10, F = 10) in two different stabilization conditions, with the TFJ
      stabilized and without the TFJ stabilized. A 2 x 2 analysis of variance was used
      to test for the effects of stabilization condition and gender on hip rotation
      measures. A significant interaction of gender and stabilization condition was
      obtained. Women displayed more hip rotation when the TFJ was not stabilized (M =
      41.03 degrees , SD = 6.53 degrees ) than when the TFJ was stabilized (M = 35.05
      degrees ; SD = 5.12 degrees ). Men displayed no difference in ROM between the two
      stabilization conditions (not stabilized: M = 39.07 degrees , SD = 4.87 degrees ;
      stabilized: M = 37.60 degrees , SD = 5.12 degrees ). To avoid measurement error
      of hip rotation ROM, use of the tibia as a lever to produce passive hip rotation
      should be used with caution, particularly in women.

PMID- 18075906
TI  - Are elderly pedestrians allowed enough time at pedestrian crossings in Cape Town,
      South Africa?
AB  - A descriptive, cross-sectional analytical study was conducted to determine
      whether the recommended walking speed of 1.2 ms(-1) would allow elderly
      pedestrians to safely clear pedestrian crossings in Cape Town, South Africa. Male
      and female volunteers (n = 47), aged 65-93 years and resident in four homes for
      older persons, were recruited. Pedestrian clearance intervals at 40 traffic
      lights within 5-km radius of the selected homes were measured. The mean walking
      speed required at these traffic lights was 0.86 +/- 0.32 ms(1). The maximal
      walking speed over 12 m was measured without carrying any load and when carrying
      a predetermined weight of an average shopping bag. Participants' emotions
      associated with pedestrian road safety were also assessed through an interview.
      The mean maximal unloaded and loaded walking speeds were 1.36 +/- 0.31 ms(-1)
      (0.73-2.03 ms(-1)), and 1.36 +/- 0.33 ms(-1) (0.58-2.12 ms(-1)), respectively.
      Over 30% of the participants walked slower than the recommended walking speed of
      1.2 ms(-1). Participants felt that traffic lights did not allow for sufficient
      time to cross roads (51.1%) and reported emotions of apprehension (44.7%),
      anxiety (17.0%), and fear (10.6%) when crossing. A review of traffic planning and
      public policy is recommended to ensure older pedestrians safely clear pedestrian
      crossings.

PMID- 18075907
TI  - Rehabilitation of a glenohumeral instability utilizing the body blade.
AB  - Traditional rehabilitation for shoulder dislocation has a success rate of only
      20%. The body blade has been hypothesized to strengthen the muscles stabilizing
      the shoulder girdle by training the contractile tissues directly and also
      indirectly affecting the joint and surrounding noncontractile tissues when
      responding to rapid positional changes and mechanical energy. Shoulder
      dislocation negatively affects both the active (musculature) and passive (joint
      and ligaments) stabilizers of the glenohumeral joint. Therefore, the purpose of
      this case report was to evaluate the efficacy of therapeutic exercise using the
      body blade in the conservative management of an individual with glenohumeral
      instability. The patient, an 18-year-old male, dislocated his left shoulder after
      a wave crashed on top of him. Intervention included therapeutic exercise using
      the body blade. Measures were taken at examination, re-evaluation (6th visit),
      and discharge (11th visit). According to the 11-point numeric pain rating scale,
      worst pain was reduced from 4 to 0. Glenohumeral ROM measures at discharge were
      all within normal range except external rotation (deficit of 10 degrees),
      compared to the initial ROM deficits of 10-35% of noninvolved values. Post
      intervention strength, as assessed by handheld dynamometry, revealed deficits
      only in scapular retraction compared to the uninvolved side (21% compared to an
      initial deficit of 39%). Other muscle groups showing deficits from 20% to 40% at
      initial examination exceeded the comparative strength of the other limb at
      discharge. The SPADI and WOSI scores were reduced from 13 to 0 and 482 to 46,
      from initial examination to discharge, respectively. Furthermore 6 months post
      episode of care the patient reported no recurrent dislocation of the involved
      shoulder. The success rate of an exercise program with individuals who have
      dislocated their glenohumeral joint is poor. After 11 visits of physical therapy
      using the body blade the patient improved in ROM, strength, and function.

PMID- 18075908
TI  - Outcomes following plyometric rehabilitation for the young throwing athlete: a
      case report.
AB  - The current literature offers limited evidence supporting sport-specific
      plyometric rehabilitation for young throwing athletes. The purposes of this case
      report were to 1) describe the focused differential diagnosis of a young throwing
      athlete with shoulder pain and 2) use previously validated, region-specific,
      health-related quality of life measures to describe clinical outcomes for a
      rehabilitation program that included sport-specific, plyometric training. The 13
      year-old male patient presented in this case report experienced a sudden onset of
      right shoulder pain while pitching in a baseball game. On physical examination,
      this patient demonstrated shoulder pain, pain with palpation of the infraspinatus
      and teres minor muscles, decreased strength of the infraspinatus and teres minor
      with resultant impaired rotator cuff performance, and signs consistent with
      anterior shoulder instability. Early rehabilitation consisted of modalities for
      pain relief and therapeutic exercises to improve strength. In the return to sport
      phase of rehabilitation, the patient performed sport-specific plyometric
      exercises that were progressed in difficulty based on the patient's report of
      pain and muscle soreness. Health-related quality of life was assessed by using
      the Shoulder Pain and Disability Index (SPADI) and the sports module of the
      Disability of Arm, Shoulder and Hand (DASH) questionnaires. A standard error of
      measurement (SEM)-based criterion was used to determine if the patient
      demonstrated meaningful changes in outcome measures. The patient did not
      demonstrate meaningful improvement in pain or general disability with the SPADI.
      The patient did demonstrate a meaningful improvement in sport-specific function
      with the DASH. It is possible that sport-specific plyometric rehabilitation may
      have provided additional benefit for this athlete's ability to return to sport,
      but definite conclusions regarding treatment effectiveness are limited by the
      case report design. Properly designed studies investigating the benefits of sport
      specific plyometric rehabilitation are warranted before the effectiveness of
      these techniques can be determined.

PMID- 18075911
TI  - Community-based prevention of alcohol problems: addressing the challenges of
      increasing deregulation of alcohol.
AB  - This article focuses on the erosion of alcohol management policies and the
      implications for local prevention efforts. It draws lessons from three large
      scale multi-year multi-site programs in Canada, e.g., local addiction prevention
      projects, heart health programs, and tobacco control experiences. It explores
      five themes: getting alcohol on the agenda and implementing effective local
      responses to alcohol problems; assessing conceptual frameworks in order to
      identify the essential components of an effective prevention strategy; developing
      a system of local prevention initiatives that give priority to long-lasting
      structural changes; generating accurate information on alcohol-related damage in
      order to set priorities; and developing a prevention action plan in order to
      support local initiatives.

PMID- 18075912
TI  - Community control of alcohol and drug risk environments: the California
      experience.
AB  - This article describes California community (city, county) uses of local powers
      and resources to prevent alcohol and other drug (AOD) problems by managing AOD
      risk environments in retail, public, and social domains. The article presents a
      promising framework used in several counties dedicated to community environment
      approaches to prevention. A case example of its application is provided. The
      framework has developed locally since the mid 1980s through AOD prevention
      demonstration grant research, policy advocacy, and state support for local
      initiatives. Data for this article come from the author's experience observing
      and consulting with California cities and counties over 25 years.

PMID- 18075913
TI  - Aboriginal community alcohol harm reduction policy (ACAHRP) project: a vision for
      the future.
AB  - Four First Nation communities in Ontario, Canada, formulated alcohol management
      policies between 1992 and 1994. An alcohol management policy is a local control
      option to manage alcohol use in recreation and leisure areas. Survey results
      indicate that decreases in alcohol use-related problems related to intoxication,
      nuisance behaviors, criminal activity, liquor license violations, and personal
      harm were perceived to have occurred. Furthermore, having policy regulations in
      place did not have an adverse effect on facility rentals. Band administrators and
      facility staff in each community felt the policy had had a positive effect on
      events at which alcohol was sold or served.

PMID- 18075914
TI  - Community action--challenges and constraints--implementing evidence-based
      approaches within a context of reorienting services.
AB  - Community action on alcohol use-related projects face significant challenges in
      focusing efforts where they are most likely to be effective--on environmental
      strategies for optimum impact and sustainable institutional change. Reorienting
      and enhancing the efforts of existing services is a crucial issue for all
      countries with limited resources. This paper evaluates the use of a public health
      partnerships model to reorient resources and enhance cross sector collaboration
      to reduce alcohol consumption-related harm in a large New Zealand city from 2001
      2004. The evaluation assessed changes in the management practices of
      participating health provider organisations, the reorientation of activities and
      the redeployment of provider resources, in light of evaluation evidence from
      collaborative initiatives undertaken by key stakeholder organisations. Despite
      the considerable challenges inherent in reorienting existing health sector
      resource and encouraging more evidence-based practice, this evaluation found
      encouraging signs of positive systemic changes, both within the health sector and
      with external stakeholders, in the redirection of priorities and resources. The
      focus on collaborative environmental strategies has also contributed to some
      limited, but promising structural changes to reduce harm in the licensed alcohol
      availability, accessibility and promotion environment.

PMID- 18075915
TI  - Effects of a community-based drug use prevention program targeting licensed
      premises.
AB  - This study evaluated the effects of a community-based drug use prevention program
      on the frequency with which doormen at licensed premises intervene in cases of
      obviously drug use-impaired patrons. Doormen were trained in recognizing signs of
      drug use impairment to be able to stop drug use-impaired patrons to enter the
      premises. The study included 28 trendy nightclubs in Stockholm, Sweden, that used
      doormen to screen patrons. Two male actors were instructed to act as if they were
      obviously drug use-impaired (cocaine/amphetamines) while attempting to enter
      nightclubs. Data were collected at pretest when 40 entry attempts were made
      (2003) and posttest (2004) when 48 attempts were made. At follow-up, the doormen
      intervened in 27% of the attempts, a significant improvement compared to the
      intervention rate of 7.5% at baseline. The results indicate that the intervention
      has had effect on doormen's behavior. However, in the majority of the attempted
      visits, the doormen still did not intervene. Limitations of the study were the
      lack of a control group and problems with identifying the training status for the
      individual doormen. Further research is necessary to explore the effectiveness of
      community-based drug use prevention programs targeting licensed premises.

PMID- 18075916
TI  - The use of an evidence-based community action intervention to improve age
      verification practices for alcohol purchase.
AB  - Alcohol purchase surveys were undertaken as part of two New Zealand community
      action projects (one in a large metropolitan area and one in a small town) that
      aimed at reducing alcohol consumption-related harm for young people. Baseline
      surveys in both places indicated poor age verification practices. The two follow
      up surveys in the metropolitan area showed a decrease in sales made without age
      identification between 2002 (60%) and 2003 (46%). However, an increase between
      2003 (46%) and 2004 (55%) occurred. In the metropolitan area, regulatory staff in
      three out of seven jurisdictions increased enforcement due to the 2002 survey and
      follow-up work; this did not happen following the 2003 survey. In the small town,
      results indicated positive changes in verification practices over time. In
      addition, licensee meetings, host responsibility training, and a regional project
      all occurred following the surveys. The surveys have also had important indirect
      effects. Closer monitoring and enforcement activity due to the surveys has
      contributed to the amendment of alcohol legislation in New Zealand.

PMID- 18075917
TI  - School leaver (graduate) celebrations in Margaret River, Western Australia: a
      community approach to management.
AB  - In recent years, an increasing number of young Western Australians have chosen
      the tourist town of Margaret River, about 300 kilometers south of the Perth, as
      the place to celebrate completing school. Typically, the celebrations involve
      intense socializing and considerable binge drinking. In 2001, the community
      developed a comprehensive management strategy to minimize the impact of the
      celebrations, while still facilitating an enjoyable experience for the leavers
      (recent graduates). This incorporated community members providing supervised
      activities for the leavers. Evaluation of the intervention employed a mixed
      methodology, comprising surveys of school leavers, interviews with community
      stakeholders, and participant observation. The findings indicated that the
      leavers generally got what they wanted from the experience and the community felt
      it had maintained control. Providing activities built a relationship between the
      leavers and the community and seemed important in minimizing problems for both
      groups. An added bonus was the community developed greater confidence and
      capacity.

PMID- 18075918
TI  - What next? Sustaining a successful small-scale alcohol consumption harm
      minimization project.
AB  - Engaging communities in alcohol consumption-related action projects requires the
      application of a range of flexible and responsive evidence-based methods. These
      include: establishing collaborative relationships, implementing strategies to
      improve age verification practices, encouraging organizational change, and
      raising awareness of local alcohol issues. The focus of this article is the
      sustainability of an alcohol harm minimization project for young people in Hawera
      (a small New Zealand town) that has produced some encouraging results. The Hawera
      Alcohol and Young People project began in 2000 along with external formative and
      impact evaluation components. This article will draw on the evaluation findings
      to date and the experience of community action projects in New Zealand to explore
      what makes a sustainable community action project and to examine the extent to
      which this has been achieved by the Hawera Alcohol and Young People project. The
      limitations of the study are noted.

PMID- 18075919
TI  - Archival data: collection and use in community alcohol projects.
AB  - Archival data are considered useful for identifying problem areas, assessing
      levels of problems, and evaluation of interventions. However, few publications
      describe the process of collecting them and related potential obstacles. For the
      Safer California Universities study, archival data is expected to play a major
      role in identifying problem settings and the extent of alcohol use-related
      problems on the campuses. The project has experienced a number of obstacles in
      collecting these data. This article discusses strategies for collecting data,
      obstacles related to collecting them, solutions to these obstacles, and
      communication with partners on the campuses. The study's limitations are noted.

PMID- 18075920
TI  - Involving stakeholders in the evaluation of community alcohol projects: finding a
      balance between subjective insight and objective facts.
AB  - The role played by key community representatives in the evaluation of community
      alcohol projects differs according to the evaluation paradigm adopted. In
      evaluations that adopt a positivist, experimental design they are cast in the
      role of independent informants. In post-positivist evaluations they are seen as
      having an interest in the evaluation and accordingly are considered active
      stakeholders. However, the degree to which stakeholders can be actively engaged
      in an evaluation varies considerably along a number of dimensions. Four
      dimensions of the stakeholder role--stakeholder inclusiveness, participation
      mode, participation frequency, and evaluation role--are examined in the context
      of eight evaluation theories. This is integrated into a model that links these
      dimensions to an object-subject continuum of stakeholder involvement. The model
      facilitates systematic consideration of these dimensions and will assist
      evaluators in achieving their desired balance of subjective insight and objective
      fact.

PMID- 18075921
TI  - The organization of a community: community-based prevention of injecting drug use
      related health problems.
AB  - In the 1980s, injection drug users in Australia mobilized and organized as
      communities to prevent the transmission of HIV/AIDS, hepatitis C, and other
      injecting-related harms. This article provides a brief history of the development
      and role of IDU communities in the prevention of drug use-related harms over the
      past 20 years and introduces the genesis of a new program that aims to improve
      peer-based, community-organized prevention and harm reduction initiatives. The
      project's limitations are noted and future needed research is suggested.

PMID- 18075922
TI  - Establishing an Italian general practitioner brief intervention pilot project for
      problem drinkers.
AB  - This national pilot project commenced in 2004. It was promoted by the Istituto
      Superiore di Sanita and financed by the Italian Ministry of Health. The Italian
      Society of General Practitioners supported implementation of the study in general
      medical practitioner settings and coordination was undertaken by the Alcohol
      Centre of the University Hospital of Florence. The objectives of the study are to
      create a brief intervention package, suitable for use within the Italian primary
      health care system for screening and treating "hazardous drinkers"; to survey
      alcohol consumption in a sample of the population aged 18 or over, who the
      general practitioners assessed as suitable for brief intervention using the
      project's instruments; to conduct an experimental trial of brief intervention
      procedures, with "hazardous drinkers" randomly allocated to intervention or
      control conditions; to assess the effectiveness of brief intervention as a
      primary preventive measure. The early stage of this study concentrated on
      creating a strong research partnership to foster the involvement of general
      medical practitioners on a national scale. Subsequently, resources were devoted
      to the creation of the brief intervention package, including support material and
      the training of the general medical practitioners in its implementation.

PMID- 18075923
TI  - Preventing alcohol-related problems in community sports clubs: the good sports
      program.
AB  - Community-based sporting clubs in Australia are often sites of unregulated,
      problematic and unsafe drinking. The Good Sports program, initiated in Victoria
      in 2001, offers such clubs a model of incremental change designed to eliminate
      harmful drinking practices and establish safer norms of alcohol use. The Good
      Sports model was developed in situ over a period of 5 years and is currently
      operating in 1600 sporting clubs across Australia. It has strong face validity
      and is supported by sporting organizations and key stakeholders including public
      health, law enforcement, road safety, and local government. The article outlines
      the model, explains early evaluation results, and identifies challenges for the
      future.

PMID- 18075924
TI  - A system for evaluating local alcohol and drug use prevention initiatives.
AB  - Local alcohol and drug use prevention in Sweden has witnessed a substantial surge
      in recent years, with government funding for local coordinators in every
      municipality. Whether this has contributed to the recent decline in alcohol use
      among young people is unknown. The ESAPP project evaluates local alcohol and drug
      prevention in the 18 municipalities that comprise Stockholm. In order to obtain
      knowledge of prevention activities and their role in outcomes and to stimulate
      sharing of experiences, a Web-based reporting system was developed in
      collaboration with the local coordinators. There has been considerable variation
      in the use of this reporting system and its potential has not been realized.

PMID- 18075925
TI  - A six-community prevention trial to reduce alcohol and drug use-related problems
      in Sweden: planning and early findings.
AB  - The objective of this study was to evaluate a research and development project to
      reduce alcohol and drug use-related problems, conducted during 2003-2005, in six
      urban and rural municipalities in Sweden, Umea, Kramfors, Solna, Kalmar, Laholm,
      and Lund. The development of alcohol and drug use trends and patterns will be
      followed through 2008 in the six targeted intervention communities and in the six
      matched control communities. The evaluation includes archival data, survey data,
      observational data, as well as process measures. The six communities have
      gradually reoriented their thinking about prevention from a single focus on youth
      activities to a broader approach involving the whole population. The project's
      and the study's limitations are noted and future needed research is suggested.

PMID- 18075926
TI  - Preliminary evaluation of the educational strategy of a community alcohol use
      action research project in Scandicci (Italy).
AB  - A community project aiming to promote responsible drinking and to prevent alcohol
      use-related problems in three districts of Scandicci, a town west of Florence,
      was undertaken between 2000 and 2004. The community totaled 21,851 residents.
      Among other initiatives, 8,000 carousels that provided information on different
      levels of alcohol consumption and more than 1,000 prints of nine drawings by
      local school children that promoted moderate consumption were distributed in the
      community, respectively, during February-July 2002 and May-June 2003. These
      formed part of a community educational strategy, spreading messages in keeping
      with the project's aims. Project process and impact evaluation studies documented
      firstly that the carousel was visible, interesting, and retained by the community
      members one year after distribution, while the children's drawing prints were
      visible and also retained some months later. Secondly, both educational tools
      were effective in mobilizing the local population because they were locally
      produced, widely distributed, and displayed in prominent community locations.
      Thirdly, a change in community opinion occurred during the course of the project
      from a more rigid idea in 2000 that only alcoholism is a problem toward a more
      comprehensive understanding in 2003 of community risk from alcohol consumption.

PMID- 18075927
TI  - The Trelleborg project: a process evaluation of a multi-sector community
      intervention to reduce alcohol consumption and related harm.
AB  - The Trelleborg project ran between 1999 and 2002. This article describes and
      analyzes the processes relating to institutionalization and social change, and
      their consequences, within the project. The research, funded by the Swedish
      National Institute of Public Health, was based on qualitative data collected
      during the project, including focused interviews with 12 key individuals, five
      focus group interviews, two evaluation seminars, and a large number of meeting
      minutes. The article concludes that positive interaction between organization
      elites is a prerequisite for institutionalization. However, the elites within an
      organization also have to take external pressures into account when transforming
      an ad hoc initiation into sustained activity.

PMID- 18075928
TI  - YouthAccess to Alcohol: early findings from a community action project to reduce
      the supply of alcohol to teens.
AB  - The Youth Access to Alcohol (YATA) project was implemented in 2002 by the Alcohol
      Advisory Council of New Zealand (ALAC) in thirty communities in New Zealand, with
      the aim of reducing the harm experienced by young people as a result of alcohol
      misuse in New Zealand through reducing the supply of alcohol by adults to young
      people. The communities include a mix of rural and urban from both Islands in New
      Zealand. The project uses a community action approach, which has included setting
      up collaborative partnerships of key agencies, the delivery of key strategies,
      and multimedia awareness raising campaigns. The communities are encouraged to
      identify unique issues in their community regarding alcohol abuse and young
      people and to develop action plans incorporating a range of strategies that
      include tested strategies as well as innovative ideas. Communities are trained to
      implement several tools to monitor changes in their community over time. The
      study's limitations are noted and future needed research is suggested.

PMID- 18075929
TI  - Implementing a national alcohol consumption prevention program at the local
      level: what does early evaluation tell us?
AB  - The current Swedish national plan for preventing alcohol consumption-related
      problems puts greater emphasis on community-level prevention measures. This
      report describes early results from the implementation of this plan in the county
      of Vastra Gotaland, in southwestern Sweden. During 2002-2004 interviews were
      conducted with the main project representative in each of the county's 49
      municipalities. In addition, more extensive data gathering, involving interviews
      with a broad range of stakeholders and systematic examination of project-related
      documentation, was undertaken in four representative municipalities. Findings
      indicated that community* alcohol consumption prevention has been strengthened
      and that the activity level is high in all municipalities, especially in relation
      to youth. However, problematic alcoholic beverage consumption by adults was
      rarely targeted; the limited resources were dispersed over too many projects;
      there was too little collaboration between stakeholding authorities and adherence
      to evidence-based practice still is lacking.

PMID- 18075930
TI  - We do what we think is the best--a content analysis of experiences of alcohol
      problem prevention in Sweden. A short report.
AB  - This short report describes an ongoing project whose aim was to explore how
      respondents from local institutions in a Swedish municipality describe their
      efforts in preventing alcohol consumption and related problems. Data were
      collected in focus group interviews, conducted during 2003 with key informants,
      comprising middle-ranking civil servants from different administrative sectors
      such as school, social welfare, and the public health office, in four Swedish
      municipalities: one city district, one town, and two small municipalities. We
      identified low knowledge of evidence-based methods for prevention of alcohol
      consumption-related problems and a lack of consistent focus on strategies known
      to be effective. The main target group for preventive efforts was identified as
      young people and the most common setting mentioned was the schools. Further, the
      key informants appeared to regard a wide range of activities as being community*
      alcohol and drug use prevention. Generally these activities also lacked
      specification. Increased knowledge of alcohol and drug use prevention methods
      that are effective at the local level is needed within Swedish municipalities, as
      is greater understanding of how to implement those methods.

PMID- 18075931
TI  - Dissemination of prevention: community action targeting alcohol use-related
      problems at licensed premises.
AB  - In 2003, a community action program targeting alcohol use-related problems at
      licensed premises was disseminated to municipalities in Stockholm County. The
      intervention program includes local mobilization, training in responsible
      beverage service, and stricter enforcement of extant alcohol laws. This research
      studies the dissemination process, which was based on Diffusion of Innovations
      Theory. The communities followed a systematic model for dissemination: engaging a
      local coordinator, conducting interviews with owners of licensed premises,
      creating an action group, presenting results from studies to the local media, and
      initiating training in responsible beverage service. Evaluation of uptake is
      based on meeting minutes from local action groups and activity reports.
      Preliminary results indicate that the dissemination strategy has been fairly
      successful. Half of the communities (7 of 14) contacted are implementing the
      model program. Further research is needed to more fully explore the potential of
      the use of the Diffusion of Innovations Theory, taking into consideration
      different stages of community readiness.

PMID- 18075932
TI  - Themes from the symposium.

PMID- 18075934
TI  - A nonparametric method for accommodating and testing across-site rate variation.
AB  - Substitution rates are one of the most fundamental parameters in a phylogenetic
      analysis and are represented in phylogenetic models as the branch lengths on a
      tree. Variation in substitution rates across an alignment of molecular sequences
      is well established and likely caused by variation in functional constraint
      across the genes encoded in the sequences. Rate variation across alignment sites
      is important to accommodate in a phylogenetic analysis; failure to account for
      across-site rate variation can cause biased estimates of phylogeny or other model
      parameters. Traditionally, rate variation across sites has been modeled by
      treating the rate for a site as a random variable drawn from some probability
      distribution (such as the gamma probability distribution) or by partitioning
      sites to different rate classes and estimating the rate for each class
      independently. We consider a different approach, related to site-specific models
      in which sites are partitioned to rate classes. However, instead of treating the
      partitioning scheme in which sites are assigned to rate classes as a fixed
      assumption of the analysis, we treat the rate partitioning as a random variable
      under a Dirichlet process prior. We find that the Dirichlet process prior model
      for across-site rate variation fits alignments of DNA sequence data better than
      commonly used models of across-site rate variation. The method appears to
      identify the underlying codon structure of protein-coding genes; rate partitions
      that were sampled by the Markov chain Monte Carlo procedure were closer to a
      partition in which sites are assigned to rate classes by codon position than to
      randomly permuted partitions but still allow for additional variability across
      sites.

PMID- 18075935
TI  - Psychosocial rehabilitation: approach of choice for those with serious mental
      illnesses.

PMID- 18075936
TI  - Outcome of community-based rehabilitation program for people with mental illness
      who are considered difficult to treat.
AB  - This observational study investigated the outcomes of a community-based
      rehabilitation program that was designed to enhance social functioning, social
      inclusion, and well-being of people with mental illness who were considered
      treatment failures by psychiatric professionals in Italy. Of the 144 patients who
      entered the program, 131 started the program and 109 completed either 12 or 18
      months of treatment. Illness severity was assessed by the Health of the Nation
      Outcome Scales (HoNOS) and social functioning by the Social and Occupational
      Functioning Assessment Scale (SOFAS). On the HoNOS, 33% of patients showed
      reliable change. On the SOFAS, 27% showed reliable change, although the change
      was substantial for few patients. Over time, patients showed moderate but
      significant improvements on the HoNOS and SOFAS. The HoNOS subscales concerning
      interpersonal relationships and social inclusion showed significant change. Very
      isolated people with mental illness gained some advantages from this
      rehabilitation program that was based on a close relationship with a key worker;
      however, the program duration may have been inadequate to produce substantial
      changes. Our findings warrant further research based on controlled studies.

PMID- 18075937
TI  - Effects of participation in consumer-operated service programs on both personal
      and organizationally mediated empowerment: results of multisite study.
AB  - The number of empowerment-oriented consumer-operated service programs (COSPs) in
      mental health has increased dramatically over the past decade; however, little
      empirical evidence exists about the effects of such programs on their intended
      outcomes. This study examined the effects of COSPs on various aspects of
      empowerment within the context of a multisite, federally funded, randomized
      clinical trial of COSPs. Results suggest that the individuals who received the
      consumer-operated services perceived higher levels of personal empowerment than
      those in the control intervention; overall, effect sizes were very modest when
      all sites were examined together in intent-to-treat analyses. However, we noted
      variations in outcomes by intensity of COSP use and also by study site, which
      suggest that specific programs had significant effects, while others did not. The
      implications of these results for the mental health field and for service
      providers and policy makers are discussed.

PMID- 18075938
TI  - Family contact, experience of family relationships, and views about family
      involvement in treatment among VA consumers with serious mental illness.
AB  - Family psychoeducation is a highly effective, but underused, evidence-based
      practice in the treatment of schizophrenia and other serious mental illnesses.
      This study examined views about family relationships and family participation in
      care among a sample of 69 consumers with serious mental illness receiving
      treatment within the Department of Veterans Affairs healthcare system. We found
      that younger consumers and those with higher levels of psychiatric symptoms were
      more likely to report family conflict and distress. Of participating consumers,
      67% wanted family participation in their psychiatric treatment and those with at
      least weekly contact with family were more likely to want family participation.
      Consumers endorsed a number of barriers to family participation in their mental
      health treatment, including their own concerns about privacy and burdening family
      and skepticism that family involvement would be helpful. We discuss implications
      of these findings for the implementation of evidence-based family programs,
      including efforts toward development of a novel intervention that will address
      consumers' concerns and promote effective family participation in care.

PMID- 18075939
TI  - Assertive community treatment--issues from scientific and clinical literature
      with implications for practice.
AB  - This review describes Assertive community treatment (ACT), an integral component
      of the care of persons with severe mental illness. Drawing on research from North
      America, Australasia, and Britain, we summarize the current evidence base for ACT
      and examine the trends and issues that may affect practice. Strong evidence
      supports the fidelity standardization, efficacy, effectiveness, and cost
      effectiveness of ACT models in psychiatry. Yet, significant methodological
      problems and issues affect implementation. The evidence indicates that the ACT
      model is one of the most effective systematic models for organizing clinical and
      functional interventions in psychiatry. Effective systems based on the ACT model
      meet more ACT fidelity criteria; are often noncoercive; do not rely on compulsory
      orders; may rely on a wider range of interventions than just medication
      adherence, including vocational and substance abuse rehabilitation; contain other
      evidence-based interventions and more mobile in vivo interventions; involve
      individual and team case management; may involve consumers as direct service
      providers; and have an interdisciplinary workforce and support structure within
      the team, providing some protection from work-related stress or burnout.

PMID- 18075940
TI  - Is learning potential associated with social skills in schizophrenia?
AB  - Cognitive deficits are a primary factor in the social and functional impairments
      characteristic of schizophrenia and an important predictor of treatment success
      in psychosocial rehabilitation. This study examined the association between
      abstract reasoning and social functioning by assessing whether learning potential
      on the Wisconsin Card Sorting Test (WCST) relates to changes in social competence
      following social skills training (SST). Fifty-six veterans with schizophrenia or
      schizoaffective disorder completed a series of assessments followed by eight SST
      sessions. To evaluate learning potential, we assessed participants with the WCST
      and Category Test (CT), taught them a training protocol for the WCST, and
      retested on both measures. Participants learned the WCST, generalized this
      learning to improve their performance on the CT, and retained these gains for
      several weeks. Participants showed small improvements on the Maryland Assessment
      of Social Competence (MASC), but WCST learning potential and CT generalization
      were unrelated to improvement on the MASC.

PMID- 18075941
TI  - Effects of co-occurring disorders on employment outcomes in a multisite
      randomized study of supported employment for people with severe mental illness.
AB  - Effects of co-occurring disorders on work outcomes were explored among
      individuals with severe mental illness who were participating in a multisite
      randomized study of supported employment. At seven sites, 1,273 people were
      randomly assigned to an experimental supported employment program or a control
      condition and followed for 2 years. Multivariate regression analysis examined
      work outcomes including earnings, hours worked, and competitive employment, as
      well as whether psychiatric disability was disclosed to coworkers and
      supervisors. Individuals with any comorbidity had lower earnings and were less
      likely to work competitively. Those with physical comorbidities had lower
      earnings, worked fewer hours, and were less likely to work competitively.
      Disclosure was more likely among those with both cognitive and physical
      comorbidities, as well as those with learning disabilities. Competitive
      employment was less likely among those with intellectual disability, visual
      impairment, and human immunodeficiency virus/acquired immuno-deficiency syndrome.
      The experimental condition was positively related to all outcomes except
      disclosure. The results suggest that, with some exceptions, comorbidities affect
      employment outcomes, requiring tailored services and supports to promote
      vocational success.

PMID- 18075942
TI  - Adding contingency management intervention to vocational rehabilitation: outcomes
      for dually diagnosed veterans.
AB  - In this random-assignment trial, we evaluated the efficacy of using a contingency
      management (CM) intervention to enhance job acquisition and tenure among
      participants of a vocational rehabilitation (VR) program. The CM intervention
      offered participants cash incentives up to $1,170 for completing tasks related to
      sobriety and job search and maintenance. Participants were 100 veterans with
      comorbid psychiatric disorders and substance dependence who were randomly
      assigned either to VR only or VR + CM. Relative to participants in the VR-only
      group, those in the VR + CM group showed more intense job searches and
      transitioned to competitive employment faster and at higher rates. No significant
      difference was found in job tenure, though this may be due to the limited follow
      up period. Abstinence rates were significantly better in the VR + CM group during
      the first 16 weeks of follow-up but not significantly different in subsequent
      follow-ups. No relationship was found between relapse and employment. These
      results suggest that rehabilitation outcomes may be enhanced by adding CM to
      current programming or by restructuring traditional work-for-pay contingencies to
      include direct financial rewards for achievement of clinical goals.

PMID- 18075943
TI  - Dissemination of supported employment in Department of Veterans Affairs.
AB  - The dissemination of complex innovative practices is one of the major challenges
      of mental health service organizations. Although substantial progress has been
      made in the development of evidence-based practices for people with severe mental
      illness, development of approaches for the large-scale dissemination of such
      practices has lagged. In 2004, the Veterans Health Administration began a
      national dissemination effort of supported employment (SE). Concomitant with the
      clinical initiative, a research project was funded to study the factors that
      promote successful program implementation through an evaluation of the
      effectiveness and cost-effectiveness of two levels of training in the evidence
      based practice of SE. This article reviews the dissemination effort and
      associated research project. This initiative represents the largest dissemination
      effort of any psychosocial rehabilitation model to date in any single healthcare
      system in the United States. We review the dissemination plan, including
      development of a mentor-trainer system at two intensity levels, regular on-site
      and telephone training and supervision, ongoing fidelity evaluation, and national
      outcomes monitoring with a Web-based data collection system.

PMID- 18075944
TI  - Bridging science to service: using Rehabilitation Research and Training Center
      program to ensure that research-based knowledge makes a difference.
AB  - The challenge of bridging science to service is increasingly visible in the
      healthcare field, with emphasis on the influence of evidence-based knowledge on
      both policy and practice. Since its inception more than 40 years ago, the
      Rehabilitation Research and Training Center (RRTC) program has provided grants
      for both research and training activities designed to ensure that research
      knowledge is translated into practice. The RRTC program is unique in that its
      mission and funding have always required that both time and money be invested in
      the translation and dissemination of research-generated knowledge to users in the
      field, i.e., decision makers and practitioners. Boston University's Center for
      Psychiatric Rehabilitation has been an RRTC for more than 25 years and provides
      an example of the effect of the RRTC program in bridging science to service. The
      Center's mission as an RRTC has been to develop and transfer research knowledge
      to decision makers and practitioners who can then inform change and promote
      progress in mental health disability policy and practice. This article reviews
      five basic dissemination and utilization principles for overcoming the most
      common barriers to effective dissemination of evidence-based knowledge and
      provides examples of the Center's activities related to each principle. In
      addition, a knowledge-transfer framework developed by the Center to organize
      dissemination and utilization efforts is described.

PMID- 18075945
TI  - Team approach to diagnosis and management of traumatic brain injury and its
      comorbidities.

PMID- 18075946
TI  - Defense and veterans brain injury center: peacetime and wartime missions.

PMID- 18075947
TI  - Adaptation of life care planning to patients with polytrauma in a VA inpatient
      setting: Implications for seamless care coordination.

PMID- 18075948
TI  - Posttraumatic stress disorder and posttraumatic stress disorder-like symptoms and
      mild traumatic brain injury.
AB  - In this article, we review the literature on posttraumatic stress disorder (PTSD)
      and PTSD-like symptoms that can occur along with mild traumatic brain injury
      (TBI) and concussion, with specific reference to concussive injuries in the
      military. We address four major areas: (1) clinical aspects of TBI and PTSD,
      including diagnostic criteria, incidence, predictive factors, and course; (2)
      biological overlap between PTSD and TBI; (3) comorbidity between PTSD and other
      mental disorders that can occur after mild TBI; and (4) current treatments for
      PTSD, with specific considerations related to treatment for patients with mild
      TBI or concussive injuries.

PMID- 18075949
TI  - Auditory dysfunction in traumatic brain injury.
AB  - Effective communication is essential for successful rehabilitation, especially in
      patients with traumatic brain injury (TBI). The authors examined the prevalence
      and characteristics of auditory dysfunction in patients with TBI who were
      admitted to a Department of Veterans Affairs TBI inpatient unit before and after
      the onset of Operation Iraqi Freedom (OIF). In order to delineate the
      characteristics of the auditory manifestations of patients who had sustained
      blast-related (BR) TBI, we reviewed the medical records of 252 patients with TBI
      and categorized them according to admission date, either before (Group I, n =
      102) or after (Group II, n = 150) the onset of OIF. We subdivided Group II into
      non-blast-related (NBR) and BR TBI; no subjects in Group I had BR TBI. We found
      that admissions for TBI have increased 47% since the onset of OIF. In Group I,
      28% of patients with TBI complained of hearing loss and 11% reported tinnitus. In
      Group II-NBR (n = 108), 44% complained of hearing loss and 18% reported tinnitus.
      In Group II-BR (n = 42), 62% complained of hearing loss and 38% reported
      tinnitus. Sensorineural loss was the most prevalent type of hearing loss in Group
      II-BR patients. In light of the high prevalence of hearing loss and tinnitus in
      this growing population of returning soldiers, we need to develop and implement
      strategies for diagnosis and management of these conditions.

PMID- 18075950
TI  - Visual function in patients of a polytrauma rehabilitation center: A descriptive
      study.
AB  - Little is known about the visual function deficits associated with polytrauma
      injury. In this retrospective descriptive study, we examined the records of a
      clinic established to assess visual function in patients experiencing deployment
      related polytrauma. We describe the clinical findings and present a vision
      examination protocol that may be useful for screening polytrauma patients in
      other settings. Data from our sample suggested that self-reported vision
      complaints were common (74%) and confirmed that visual impairment occurred in 38%
      of all cases. When examining the mechanism of injury, we found that polytrauma
      due to blast injuries appeared to more than double the risk of visual impairment
      compared with all other polytrauma causes (i.e., motor vehicle accidents, gunshot
      and/or shrapnel, assault, falls, or anoxia). The rate of visual impairment in
      blast-related injury was 52% compared with 20% for all other sources of injury.
      Visual complaints and impairments were common in the polytrauma patients studied.
      This finding suggests that comprehensive eye examinations should be routinely
      administered, particularly when the mechanism of injury involves a blast.

PMID- 18075951
TI  - Awareness problems following moderate to severe traumatic brain injury:
      Prevalence, assessment methods, and injury correlates.
AB  - We examined the degree to which individuals with a history of moderate to severe
      traumatic brain injury (TBI) are unaware of their postinjury deficits. We also
      examined correlates between awareness problems and injury acuteness and severity
      and whether awareness problems differed across behavioral domains. Self- and
      significant other (family member) ratings on the Key Behaviors Change Inventory
      (KBCI) were examined in 36 individuals an average of 2 years post-TBI. Family
      members reported greater problems postinjury than patients did, depending on the
      behavior in question and the level of patient awareness overall. Postinjury
      awareness problems were as prevalent as other behavioral problems measured by the
      KBCI but were not universally present. Some patients exhibited no awareness
      problems, others emergent awareness, and a minority poor awareness. Correlations
      revealed that as time postinjury increased, patients showed more accurate self
      awareness than those whose injuries were more recent. Family members and patients
      agreed about preinjury functioning.

PMID- 18075952
TI  - A neuropsychiatric perspective on traumatic brain injury.
AB  - Traumatic brain injury (TBI) due to closed mechanisms causes strain injuries to
      axons that increase in number and severity as injury severity increases. Axons
      that project up from the brain stem are vulnerable, even in milder concussive
      injuries, and include axons that participate in key monoaminergic pathways.
      Although called diffuse axonal injury, the supra-tentorial injury component
      typically shows an anterior preponderance in humans. As the injury forces
      increase, cerebral contusions may be superimposed on the axonal strain injuries,
      and these contusions show an anterior preponderance as well. The chronic
      neuropsychiatric manifestations of TBI reflect this injury distribution. In the
      cognitive sphere, these manifestations almost always include power function
      disturbances marked by difficulties with cognitive processing speed,
      multitasking, and cognitive endurance. These disturbances may then be followed by
      disturbances in executive function and self-awareness as injury severity
      increases. In the behavioral sphere, mood disturbances and disorders of
      behavioral control and regulation are particularly common.

PMID- 18075953
TI  - Review of sports-related concussion: Potential for application in military
      settings.
AB  - This article reviews current issues and practices in the assessment and clinical
      management of sports-related concussion. An estimated 300,000 sports-related
      concussions occur annually in the United States. Much of what has been learned
      about concussion in the sports arena can be applied to the diagnosis and
      management of concussion in military settings. Current military guidelines for
      assessing and managing concussion in war zones incorporate information and
      methods developed through sports-concussion research. We discuss the incidence,
      definition, and diagnosis of concussion; concussion grading scales; sideline
      evaluation tools; neuropsychological assessment; return-to-action criteria; and
      complications of concussion.

PMID- 18075954
TI  - Motor impairment after severe traumatic brain injury: A longitudinal multicenter
      study.
AB  - Neuromotor impairment is a common sequela of severe traumatic brain injury (TBI)
      but has been understudied relative to neurocognitive outcomes. This multicenter
      cohort study describes the longitudinal course of neurological examination-based
      motor abnormalities after severe TBI. Subjects were enrolled from the four lead
      Department of Veterans Affairs and Defense and Veterans Brain Injury Center
      sites. The study cohort consisted of 102 consecutive patients (active duty,
      veteran, or military dependent) with severe TBI who consented during acute
      rehabilitation for data collection and completed all follow-up evaluations.
      Paresis, ataxia, and postural instability measures showed a pattern of
      improvement over time, with the greatest improvement occurring between the
      inpatient (baseline) and 6-month follow-up assessments. Involuntary movement
      disorders were rare at all time points. Two years following acute rehabilitation,
      more than one-third of subjects continued to display a neuromotor abnormality on
      basic neurological examination. Persistence of tandem gait abnormality was
      particularly common.

PMID- 18075955
TI  - Objectively assessing balance deficits after TBI: Role of computerized
      posturography.
AB  - Balance impairment, or postural instability, is a common source of residual
      physical disability after severe traumatic brain injury (TBI). Standardized
      functional measures such as the Functional Independence Measure (FIM) do not
      specifically assess balance. Furthermore, no agreement exists as to the optimal
      way to objectively measure balance problems in the TBI population. Technological
      advances have led to force-plate balance measurement known as computerized
      posturography testing (CPT). Published CPT data for severe TBI are lacking, and
      the feasibility of using CPT during rehabilitation has not been described. This
      study described CPT findings in 21 ambulatory patients with severe TBI who were
      undergoing inpatient rehabilitation at a Defense and Veterans Brain Injury
      Center. Results demonstrated the utility of CPT in detecting and quantifying
      postural instability. Comparisons with the normative database indicate that the
      sample had a high degree of balance impairment despite some participants having
      reached the ceiling of the FIM ambulation scale at discharge from the acute
      rehabilitation setting. The quantitative CPT measures are a promising way to
      characterize postural instability in severe TBI populations.

PMID- 18075956
TI  - Using International Classification of Functioning, Disability and Health to
      understand challenges in community reintegration of injured veterans.
AB  - This pilot study used the framework of the World Health Organization's
      International Classification of Functioning, Disability and Health (ICF) to
      understand the challenges faced by Operation Enduring Freedom (OEF) and Operation
      Iraqi Freedom (OIF) veterans as they reintegrate into the community. We conducted
      semistructured interviews with 14 injured veterans, 12 caregivers, and 14
      clinicians. We used ICF taxonomy to code data and identify issues. We identified
      challenges in the following ICF domains: learning and applying knowledge; general
      tasks and demands; communication; mobility; self-care; domestic life;
      interpersonal interactions, major life areas; and community, social, and civic
      life. We found many similarities between the challenges faced by veterans with
      and without polytraumatic injuries, although veterans with polytraumatic injuries
      faced challenges of greater magnitude. Identifying community reintegration
      challenges early and promoting reintegration are important mandates for the
      Department of Veterans Affairs. The findings of this study are useful in
      understanding the needs of OEF/OIF veterans.

PMID- 18075957
TI  - Community-integrated brain injury rehabilitation: Treatment models and challenges
      for civilian, military, and veteran populations.
AB  - Traumatic brain injury (TBI) is a major health problem in civilian, military, and
      veteran populations. Individuals experiencing moderate to severe TBI require a
      continuum of care involving acute hospitalization and postacute rehabilitation,
      including community reintegration and, one would hope, a return home to function
      as a productive member of the community. In the military, the goal is to help
      individuals with TBI return to active duty or make an optimal return to civilian
      life if the extent of their injuries necessitates a "medical board" discharge.
      Whether civilian, military, or veteran with TBI, individuals who move beyond the
      need to live in a facility must be reintegrated back into the community. This
      article discusses four treatment models for community reintegration, reviews
      treatment standardization and outcome issues, and describes a manualized
      rehabilitation pilot program designed to provide community reintegration and
      return to duty/work for civilians, veterans, and military personnel with TBI.

PMID- 18075958
TI  - Military and VA telemedicine systems for patients with traumatic brain injury.
AB  - Telemedicine plays a critical role within the Department of Veterans Affairs (VA)
      Veterans Health Administration by allowing the surveillance and care of patients
      who are isolated by geography, poverty, and disability. In military settings,
      telemedicine is being widely used to identify injury and illness and aid in the
      treatment, rehabilitation, and recovery of combat-wounded soldiers in theater.
      Rapid advances in both domains are transforming the way clinicians provide care,
      education, and support to patients with traumatic brain injury (TBI) and their
      families. This article discusses the military and VA telemedicine capabilities
      that are supporting the care of service members and veterans with TBI. These
      capabilities include new technologies that enhance the identification of TBI,
      management of symptoms in theater, and application of proven technologies
      (interactive video, Internet, and World Wide Web) to improve overall care
      coordination throughout military and VA systems. The impact of distance learning,
      teleconsultation, telerehabilitation, and home telehealth programs is also
      described within this context.

PMID- 18075959
TI  - Program development and defining characteristics of returning military in a VA
      Polytrauma Network Site.
AB  - The conflicts in Iraq and Afghanistan have resulted in a new generation of combat
      survivors with complex physical injuries and emotional trauma. This article
      reports the initial implementation of the Polytrauma Network Site (PNS) clinic,
      which is a key component of the Department of Veterans Affairs (VA) Polytrauma
      System of Care and serves military personnel returning from combat. The PNS
      clinic in Palo Alto, California, is described to demonstrate the VA healthcare
      system's evolving effort to meet the clinical needs of this population. We
      summarize the following features of this interdisciplinary program: (1)
      sequential assessment, from initial traumatic brain injury screening throughout
      our catchment area to evaluation by the PNS clinic team, and (2) clinical
      evaluation results for the first 62 clinic patients. In summary, this population
      shows a high prevalence of postconcussion symptoms, posttraumatic stress, poor
      cognitive performance, head and back pain, auditory and visual symptoms, and
      problems with dizziness or balance. An anonymous patient feedback survey, which
      we used to fine-tune the clinic process, reflected high satisfaction with this
      new program. We hope that the lessons learned at one site will enhance the
      identification and treatment of veterans with polytrauma across the country.

PMID- 18075960
TI  - A case of retroperitoneal ectopic pregnancy following IVF-ET in a patient with
      previous bilateral salpingectomy.
AB  - The numbers of ectopic pregnancies have increased because of the popularization
      of assisted reproductive techniques. However, the retroperitoneal space is an
      exceptional location for ectopic pregnancy because the entrance to the
      retroperitoneal space is unknown. A woman 31 years of age who had received
      bilateral salpingectomy because of a right tubal ectopic pregnancy and a left
      hydrosalpinx 4 years earlier was treated by in vitro fertilization and embryo
      transfer (IVF-ET). Ultrasonography and magnetic resonance imaging (MRI) revealed
      a gestational sac attached to the inferior vena cava in the midabdomen of the
      retroperitoneal space. Single-dose methotrexate administration was administered
      twice. However, because of sudden upper abdominal pain with a drastic decline of
      hemoglobin, an emergent laparotomy was performed. The hematoma and a gestational
      sac were removed from the aorta and inferior vena cava. Ectopic pregnancy
      following IVF-ET in a patient with bilateral salpingectomy is likely to be the
      cause of implantation at this unusual site. An unusual ectopic pregnancy has a
      high risk of life-threatening massive bleeding. Intensive transabdominal
      ultrasound scanning and whole abdominal MRI should be performed for the early
      diagnosis of unruptured ectopic pregnancy.

PMID- 18075961
TI  - Fetal hydrops associated with tumors.
AB  - Fetuses with tumors associated with hydrops have a high mortality rate.
      Relatively few survivors have this potentially fatal combination. This study
      examined the clinical and pathological findings, pathogenesis, and outcomes of
      fetuses with tumors and hydrops. One hundred and fifty-eight study cases were
      collected from the literature and from personal files. Only patients where
      adequate clinical and pathological data were given and the outcome of pregnancy
      was described were included in the study. Cardiac tumors were the majority found
      in association with fetal hydrops. Leukemia and extracardiac teratomas were next
      in frequency followed by hepatic tumors, neuroblastoma, placental, soft tissue,
      and renal tumors. The main presenting findings along with hydrops were
      hydramnios, a tumor mass, placentomegaly, and stillbirth. Most tumors were
      detected in the third trimester of pregnancy. No fetus with the diagnosis of
      cardiac rhabdomyoma, neuroblastoma, brain tumor, rhabdoid tumor, or histiocytosis
      associated with hydrops survived. Those patients with placental chorangioma,
      pericardial teratoma, and hepatic hemangioma had the best outcome. The overall
      survival rate was low: 30 of 158 (19%).

PMID- 18075962
TI  - Prediction of duration of active labor in nulliparous women at term.
AB  - We have assessed the independent predictors of duration of active labor in
      nulliparous women at term. Using a cohort of 1067 nulliparae in spontaneous labor
      at > 37.0 weeks with singleton fetuses in vertex presentation, multivariate
      analysis was used to identify independent predictors of duration of active labor.
      Duration of active labor was 4.1 +/- 2.4 hours. Stepwise linear regression
      selected 10 independent predictors of duration of active labor: gestational age
      at delivery ( P < 0.001), race ( P = 0.014), obstetric risk factors ( P = 0.022),
      amniotomy ( P < 0.001), fundal height ( P = 0.005), cervical dilation on
      admission ( P < 0.001), frequency of contractions ( P < 0.001), station of
      presenting part ( P < 0.001), oxytocin ( P < 0.001), and epidural use ( P <
      0.001). A prediction formula incorporating the 10 predictors accounted for 51% of
      the total variance of the observed duration of active labor. Ten variables are
      independent predictors of duration of active labor; when incorporated in a
      prediction formula they account for > 50% of the variability of duration of labor
      in nulliparous women.

PMID- 18075963
TI  - Apoptosis in the chorion of fetal membranes in preterm premature rupture of
      membranes.
AB  - We sought to determine if apoptosis in the chorion of fetal membranes was
      increased in patients with preterm premature rupture of membranes (PPROM) with
      histological chorioamnionitis. Using the TUNEL (terminal uridine deoxynucleotidyl
      transferase dUTP nick-end labeling) method (ApopTag Plus kit; Oncor,
      Gaithersburg, MD), apoptosis was quantified. Of the 47 subjects with PPROM, 18
      lacked sufficient chorion for quantification (confirmed by cytokeratin staining).
      In the remaining 30 subjects, fetal membranes with and without chorioamnionitis
      were examined and apoptosis was quantified. There were no differences in maternal
      age, race, insurance, cesarean rate, or gestational age between groups. The
      chorion of fetal membranes from PPROM patients with chorioamnionitis had
      significantly more apoptotic nuclei than those without chorioamnionitis (19.1
      versus 0.8; P= .005). Of the 17 subjects excluded for absence of chorion, 16
      (94%) had at least moderate chorioamnionitis. This investigation suggests that
      apoptosis is accelerated in the chorion of PPROM subjects with chorioamnionitis.
      Absence of the chorion in 37% of subjects is supportive of the hypothesis that
      inflammation accelerates cell death and destruction of the chorion.

PMID- 18075964
TI  - Analyzing retrospective data with time-varying exposure: a cautionary tale of H2
      blockers in ELBW neonates.
AB  - The objective of our study was to alert researchers to potential pitfalls
      involved in analysis of a potential association between risk factors and
      development of disease. We applied three different analytic methods --
      retrospective cohort study analyzed using logistic regression, case-control
      analysis, and survival analysis with time-dependent exposure -- to retrospective
      data showing a correlation between histamine 2 (H(2)) blocker exposure and the
      occurrence of necrotizing enterocolitis in extremely low birthweight neonates.
      Using case-control and survival analysis methods, there was an apparent increase
      in necrotizing enterocolitis following exposure to H(2) blocker treatment. The
      retrospective cohort method led to the opposite conclusion because it failed to
      account appropriately for exposure. We concluded that the choice of the analytic
      methodology used in a retrospective study is critical and should take into
      account the timing and characteristics of the risk factors and condition under
      investigation. Erroneous conclusions may be reached if inappropriate statistical
      methods are used.

PMID- 18075965
TI  - Preterm premature rupture of membrane management--inpatient versus outpatient: a
      retrospective review.
AB  - The purpose of this study was to evaluate the outcome of patients with preterm
      premature rupture of membranes (PPROM) managed as inpatients who would have been
      candidates for outpatient management by prior published criteria. A retrospective
      review of medical records of PPROM subjects enrolled in a prospective cohort
      study was performed. Similar criteria to those established in a randomized trial
      for home management of PPROM by Carlan et al were applied. Assuming local
      residence, 65 subjects met the criteria for outpatient management. Demographic
      and delivery information were collected. Of the 65 subjects, 12 (18%) delivered
      <2 hours from the sentinel event. Adverse outcomes in these 12 subjects could
      have been devastating had they been managed as outpatients. Given the
      susceptibility of these subjects to obstetric emergencies, patients with PPROM at
      a viable gestational age should be considered for management as inpatients in a
      tertiary-care facility.

PMID- 18075966
TI  - [Pneumological aspects of wind instrument performance--physiological,
      pathophysiological and therapeutic considerations].
AB  - Wind instrument performance is a notable feature in pneumology under aspects of
      ventilatory physiology and respiratory diseases. It requires an adequate
      ventilatory function combined with precise control of air flow and the ability to
      generate sufficient mouth pressures. Depending on the type of wind instrument,
      the required rates of airway pressure and air flow differ significantly. The
      cause of respiratory disease in wind instrument players may be related to these
      increased airway pressures in terms of a barotrauma. Wind instrumentalists may
      suffer from hemoptysis, laryngoceles, velopharyngeal insufficiency and
      pneumoparotitis due to their musical performance. Even the development of lung
      cancer has been assumed to be related to wind instrument playing. Controversy
      exists about implicating wind instrument use as the cause of pulmonary emphysema
      or in changes of pulmonary function, which is, however, unlikely under
      physiological aspects. Furthermore, professional wind instrumentalists may be
      impaired in their work by the side effects of anti-obstructive medication and
      respiratory infection. On the other hand, the potential therapeutic effects of
      wind instrument performance have to be considered. For asthmatic teenagers a
      significant improvement of pulmonary function and of physical and emotional
      activities could be related to wind instrument playing. Last but not least,
      didgeridoo playing was shown to be a promising alternative treatment for
      obstructive sleep apnoea syndrome.

PMID- 18075967
TI  - Insulin resistance -- the role of ethnicity: evidence from Caucasian and African
      cohorts.
AB  - The risk for insulin resistance and subsequent type 2 diabetes varies between
      different ethnic populations due to differences in the genetic and environmental
      background. However, obesity and unhealthy lifestyle, crucial determinants of
      insulin resistance, are on the rise throughout all population groups though the
      susceptibility towards those factors may differ. Up to the present day it is not
      clear whether insulin resistance is based on metabolic changes due to lifestyle
      modifications or rather an ethnic and thus genetic grounded phenomenon. Genetic
      variations in secretion products of the active fat tissue (adipokines), a
      different pathophysiology of changes in glucose metabolism and the deep impact of
      urbanization (environmental factors) are discussed as primary determinants for
      differences in manifestation of insulin resistance between Caucasian and African
      populations. These factors may be influenced or modified by a central theme:
      visceral obesity. This mini review will elaborate on these issues illustrated by
      observations from Caucasian and African cohorts.

PMID- 18075968
TI  - The health status of Russian-speaking immigrants in Germany.
AB  - INTRODUCTION: Germany developed today into a country of immigration, which
      creates an additional burden for the social security system and results in a new
      challenge for the healthcare. In the last 17 years more than two million "Russia
      Germans" have been repatriated and about two hundred thousand Jewish refugees
      have resettled in Germany from the former Soviet Union. Nevertheless relevant
      data concerning migration-related public health care are very scare. METHODS:
      Search of PubMed and Journals extracts combined with the own researches,
      analysing the health status indices of the Russian-speaking immigrants in
      Germany. RESULTS: Both repatriates of German origin and Jewish refugees
      demonstrated higher prevalence of impaired lipid metabolism in comparison with
      native population. 42 % of the 503,040 HBsAg (hepatitis B s-Antigen) carriers in
      Germany were migrants. The Jewish refugees demonstrated the highest rates of
      depression and anxiety and the highest levels of awakening cortisol. On the other
      side German resettlers showed lower cardiovascular as well as all-cause death
      rates compared to the native Germans. CONCLUSION: The development of adequate
      health care programmes to address migratory aspects as well as the establishment
      of quality standards will realistically enhance the capability of responding
      rapidly to migrant health aspects and help to tackle inequalities in health.

PMID- 18075969
TI  - Increase of beta-endorphin secretion by syringin, an active principle of
      Eleutherococcus senticosus, to produce antihyperglycemic action in type 1-like
      diabetic rats.
AB  - We employed streptozotocin-induced diabetic rats (STZ-diabetic rats) as type 1
      diabetes-like animal models to investigate the mechanism(s) of antihyperglycemic
      action produced by syringin, an active principle purified from the rhizome and
      root part S of ELEUTHEROCOCCUS SENTICOSUS (Araliaceae). Bolus intravenous (i. v.)
      injection of syringin dose-dependently decreased the plasma glucose of STZ
      diabetic rats in 30 minutes in a way parallel to the increase of plasma beta
      endorphin-like immunoreactivity (BER). Syringin enhanced BER release from the
      isolated adrenal medulla of STZ-diabetic rats in a concentration-dependent manner
      from 0.001 to 10 micromol/l. Bilateral adrenalectomy in STZ-diabetic rats
      eliminated the activities of syringin (1 mg/kg, i. v.) including the plasma
      glucose-lowering effect and the plasma BER-elevating effect. Also, syringin
      failed to lower plasma glucose in the presence of micro-opioid receptor
      antagonists and/or in the micro-opioid receptor knockout diabetic mice. In
      conclusion, the obtained results suggest that syringin can enhance the secretion
      of beta-endorphin from adrenal medulla to stimulate peripheral micro-opioid
      receptors resulting in a decrease of plasma glucose in diabetic rats lacking
      insulin.

PMID- 18075970
TI  - Relationship between leptin concentration and insulin resistance.
AB  - Available evidences suggest that leptin has inhibitory role on insulin secretion.
      The aim of the work was to examine the association between plasma leptin
      concentrations and insulin resistance in patients with gestational diabetes
      mellitus. As a cross-sectional study we recruited 741 pregnant women. The
      universal screening was performed with an oral glucose challenge test-50 g. The
      recruits with plasma glucose levels of > or = 7.2 mmol/l were diagnosed as having
      gestational diabetes mellitus if they had an impaired oral glucose tolerance test
      100 g based on Carpenter and Coustan criteria. In all pregnancies plasma insulin
      and leptin concentrations were measured. Gestational diabetes mellitus developed
      in 7% (52) of pregnancies. Elevated leptin concentrations were positively
      associated with insulin levels, BMI, and HOMA index while it was negatively
      associated with Quicky index. After adjusting for age and BMI before pregnancy,
      gestational diabetes mellitus had independent direct correlation with leptin
      concentration. Indeed, leptin level equal to or more than 20 ng/ml could help to
      predict the developing gestational diabetes mellitus. Measurement of leptin
      together with the assessment of other risk factors could help identifying women
      at risk of developing GDM.

PMID- 18075971
TI  - Effects of spironolactone on glucose transport and interleukin-6 secretion in
      adipose cells of women.
AB  - Adipose tissue inflammation and insulin resistance are central to the
      pathogenesis of the metabolic syndrome. Spironolactone, an antagonist of
      mineralocorticoid receptor, glucocorticoid receptor and androgen receptor, and
      agonist of progesterone receptor, has anti-inflammatory activity. Blockade of the
      renin-angiotensin-aldosterone system has been shown to improve glucose
      metabolism. We have investigated whether spironolactone has direct effects on
      glucose uptake and interleukin-6 secretion in human adipocytes. Spironolactone,
      but not its active metabolite canrenoic acid, significantly increased basal and
      insulin-stimulated glucose uptake in cultured IN VITRO-differentiated adipocytes
      of women, without affecting insulin sensitivity. The effect was not due to
      changes in abundance of glucose transporters 1 or 4 or in degree of cell
      differentiation. Spironolactone, but not canrenoic acid, significantly reduced
      basal interleukin-6 secretion by cultured stromal-vascular cells. These effects
      of spironolactone were not mediated by ligand-dependent antagonism of the
      mineralocorticoid, glucocorticoid, or androgen receptors. Spironolactone may have
      a novel role in increasing glucose uptake into adipose cells and attenuating
      adipose tissue inflammation, with implications for management of metabolic
      syndrome.

PMID- 18075972
TI  - Statistical analysis of effects of testosterone on purine metabolism in rat
      liver.

PMID- 18075981
TI  - [Psychiatry and neurology: clinical neurosciences].

PMID- 18075982
TI  - [The swing of psychiatry].

PMID- 18075983
TI  - [Neurocristopathies: a high incidence of cerebral dysgenesis in patients with
      Hirschsprung's disease].
AB  - INTRODUCTION: Hirschsprung's disease (HD), or aganglionic megacolon, is a
      congenital disorder that is characterised by the absence of ganglion cells in the
      submucosal and myenteric plexuses of the intestine, which is caused by the
      failure of these cells to migrate from the neural crest (neurocristopathy).
      Cerebral dysgenesis and polymalformation syndromes have been reported in
      association with HD, thus suggesting an abnormal morphogenesis. AIM: To study the
      frequency of cerebral malformations in patients with HD in our environment.
      PATIENTS AND METHODS: We conducted a retrospective study of 41,666 live newborn
      infants, over the period 1993-2003, and 17 cases of HD where identified. RESULTS:
      The incidence of HD in the health district of the province of Albacete is 1.68
      per 5,000 live newborn infants. Of the 17 patients with HD who were studied, 10
      were isolated (58.8%) and seven (41.1%) were associated to other structural
      abnormalities and psychomotor retardation. Three of the cases in this latter
      group were due to chromosome pathology (trisomy 21, Down syndrome), two were
      caused by specific polymalformation syndromes (one Mowat-Wilson syndrome and one
      possible FG syndrome), one was due to a pattern of abnormalities that did not fit
      any known syndrome, and one had a normal phenotype and isolated cerebral
      dysgenesis. In all of cases the neuroimaging studies identified cerebral
      dysgenesis that was compatible with neuronal migration disorders. CONCLUSIONS:
      The frequency of association of HD, either isolated or within the context of a
      specific malformation syndrome, with neuronal migration disorders is high
      (23.5%). We suggest a full genetic and neurological evaluation should be carried
      out in patients with HD, together with brain imaging studies in order to rule out
      the possibility of cerebral dysgenesis.

PMID- 18075984
TI  - [Differences between the neuropsychological profiles of Asperger's syndrome and
      non-verbal learning disorder].
AB  - INTRODUCTION: The validity of the Asperger syndrome (AS) diagnose continues to be
      debated due to the lack of consensus on its definition, specially regarding
      higher-functioning autism. Previous research has suggested that the
      neuropsychological profile of the non verbal learning syndrome (NVLS) might be
      utilized to sustain a differential diagnose of the AS with other diseases
      associated with development. AIM: To analyze the neuropsychological profile of
      children diagnosed with AS and compare with those obtained from children with
      NVLS. SUBJECTS AND METHODS: All cognitive domains from 15 children have been
      evaluated with an extensive variety of tests; 5 were diagnosed with AS and 5 with
      NVLS, all of them submitted to the Nino Jesus Children's University Hospital. As
      a control group, another 5 children with no pathology were evaluated. RESULTS:
      Obtained data shows significant differences between the two groups under study.
      Profile from individuals under AS shows deficit in linguistic as well as non
      verbal skills and, when compared to the control group, executive functions seem
      to be generally more altered. CONCLUSIONS: Further investigation is suggested to
      determine that the NVLS could be an explanation model for AS. On the other hand,
      we stress the need to deepen the study of the executive functions and their
      relationship with the mind's theory, as an hypothesis to explain the AS.

PMID- 18075985
TI  - [Clinical epidemiological study of vascular epilepsy].
AB  - INTRODUCTION: Little research has been conducted on vascular epilepsy (VE) in our
      environment, although some authors claim it accounts for 45% of all symptomatic
      epilepsies in persons over 60 year of age. PATIENTS AND METHODS: We obtained a
      cross-sectional sample of the hospital admissions that took place in our health
      area between 1999 and 2005 using the diagnosis-related group coding system with
      numbers 14 (specific cerebrovascular disorders, except transient ischemic attacks
      and intracerebral haemorrhages) and 810 (intracerebral haemorrhages), and
      crossing them with an admission diagnosis of epileptic seizures or symptomatic
      status epilepticus. We recruited 101 patients who had been diagnosed with VE
      (taking into account only those who had seizures two weeks after the acute
      event). This represented 9.14% of all new cases of epilepsy over that period of
      time. RESULTS: After rejecting patients who had had their stroke before 1999 and
      those for whom no accurate record of the event was available, we obtained an
      incidence of VE in ischaemic strokes of 6.5%, with a figure of 11.6% for
      haematomas. Status epilepticus was reported in 27.7% of cases. Early status
      epilepticus was associated with a mortality rate of 77.7%. CONCLUSIONS: Although
      the incidence of VE is higher than in other series that have appeared in the
      literature, our sample is too small to be able to extract data concerning
      demographic characteristics. Nevertheless, its prevalence makes it an important
      health issue that increases the rate at which resources are used and adds further
      insecurity in the case of individuals who already suffer some degree of
      disability.

PMID- 18075986
TI  - [Immune factors or depression? Fatigue correlates in Parkinson's disease].
AB  - INTRODUCTION: Fatigue is a frequent symptom in Parkinson disease (PD), but its
      pathogenesis remains obscure. Fatigue may be influenced by depression and motor
      disability, but immunological factors have been also implicated. The purpose of
      the study was to assess fatigue in PD patients in relation to depression and
      various immunological factors. SUBJECTS AND METHODS: Forty PD patients and 26
      normal matched controls were studied. Fatigue was assessed by the Fatigue
      Severity Scale (FSS). The Beck Depression Inventory (BDI) was employed for
      depression screening. The following immunological factors were estimated: a) T-
      and B-lymphocytes, T-lymphocyte subsets (helper/suppressor cells) as well as
      natural killer cells (NK); b) circulating levels of interleukins IL-1alpha, IL
      1beta, IL-6, IL-1 receptor antagonist (IL-1Ra) and tumor necrosis factor-alpha.
      RESULTS: FSS mean score was higher in PD patients compared to controls (p <
      0.01). Significant differences between patients and controls were found in the
      following immunological parameters. In PD patients: a) mean percentage of NK
      cells was higher, p < 0.01); b) IL-1beta levels were significantly increased (p <
      0.01) and IL-1Ra levels were decreased (p < 0.001). FSS correlated significantly
      to BDI (p < 0.008). Circulating Il-1Ra levels correlated to fatigue severity (p <
      0.01), but after exclusion of depressed PD subjects this correlation significance
      level dropped to p = 0.055. CONCLUSIONS: Our results indicate that fatigue is a
      common non motor symptom in PD. Immunological differences between PD patients and
      controls were observed in percentages of NK cells, IL-1beta and IL-1Ra blood
      levels. Fatigue correlated to depression and IL-Ra levels. However after
      exclusion of depressed subjects IL-1Ra levels showed only a tendency to
      significance, leaving depression as the principle correlate of fatigue.

PMID- 18075987
TI  - [Monitoring cognitive characteristics in a population with hereditary
      cerebrovascular disease (CADASIL) in Colombia].
AB  - INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is a hereditary disease that affects small
      vessels and presents with vascular episodes, neuropsychiatric disorders, migraine
      and cognitive impairment. The cognitive disorder varies according to the time
      elapsed since onset. It is a condition with a subcortical origin related to
      executive dysfunction, slowing, attention-related disorders and memory disorders.
      AIM: To define the cognitive characteristics in two neuropsychological
      evaluations of carriers of Notch3 gene mutations as compared to non-carriers
      belonging to Colombian families with CADASIL. SUBJECTS AND METHODS: The study
      followed a longitudinal, retrospective design with 140 participants, including
      both carriers and non-carriers of the mutation. Cognitive performance was
      analysed by comparing the first and the last neuropsychological evaluation
      carried out on each subject at a four-year interval. RESULTS: There were
      statistically significant differences (p < 0.05) between the two groups in the
      last evaluation, but only in some tests. Carriers and non-carriers did not
      display any significant changes between the first and the last evaluation.
      CONCLUSIONS: No differences were found between both groups in the two
      evaluations. Cognitive impairment is not observed with the passage of time in
      carriers, probably owing to the fact that most of them were young, asymptomatic
      subjects. We believe that four years' follow-up is not enough time to observe a
      significant progression in the alterations affecting the cognitive functions in
      carriers of mutations in the Notch3 gene, which causes CADASIL. We also consider
      that more sensitive cognitive tools are needed to perform the neuropsychological
      evaluation.

PMID- 18075988
TI  - [Leprosy and severe neuropathy in two native Spaniards].
AB  - INTRODUCTION: Leprosy is a widespread infectious disease in humans that is
      endemic to regions with poor sanitary conditions, especially in cases of
      overcrowding, malnutrition and bad hygiene. The disease is characterised by
      dermopathy, which is quite typical, but above all by neuropathy, which often
      becomes the most important element. In most cases, alterations to nerves are
      defined by sensory deficits that are predominantly distal and multiple neuritis
      in areas where nerve entrapment has taken place. CASE REPORTS: Two patients, both
      native Spaniards, presented largely overlapping clinical pictures, that is, a
      history of 'glove and stocking' type paresthesias and dysesthesias going back
      months or even years and functional impotence, which gave rise to a very
      pronounced gait disorder. In the two cases, the immunological situation was
      determined to be borderline lepromatous leprosy. The neurophysiological study
      revealed the presence of severe, diffuse sensory-motor axonal polyneuropathy that
      was predominantly distal, and several entrapped nerves. The dermatological
      illness was greatly improved by the treatment. The same was partially true,
      although to a satisfactory extent, of the neurological disease. CONCLUSION: We
      describe the cases of two Spaniards with borderline lepromatous leprosy with no
      past history of the disease, in whom neuropathy was the predominant symptom. We
      highlight the speed with which the neuropathies progressed, probably due to a
      change in 'polarity', and the severity of the neurological deficits in comparison
      with the dermopathy, in an unusual immunological situation. The growing number of
      native patients in the first world, even when there is no relevant history,
      suggests that we should not think of leprosy as something only occurring in
      immigrant patients from places where it is endemic, although the epidemiological
      relationship has still not been determined.

PMID- 18075989
TI  - [Neurogenesis as a therapeutic strategy to regenerate central nervous system].
AB  - INTRODUCTION: In the past few years, it has been demonstrated that the adult
      mammalian brain maintains the capacity to generate new neurons from neural
      stem/progenitor cells. These new neurons integrate into pre-existing systems
      through a process referred to as 'neurogenesis in the adult brain'. DEVELOPMENT:
      This discovery has modified our understanding of how the central nervous system
      functions in health and disease. Until today, a great effort has been made
      attempting to decipher the mechanisms regulating adult neurogenesis, which might
      help to induce neuronal endogenous cell replacement in various neurological
      diseases. CONCLUSIONS: In this revision, we will attempt to shed some light on
      the neurogenesis process with respect to diseases of the central nervous system
      and we will describe some therapeutic potentials in relation to neurodegenerative
      diseases.

PMID- 18075990
TI  - [On the reunion between neurology and psychiatry. An old neuropsychiatrist's
      reflections].
AB  - What appears in this article is nothing more than a series of reflections on
      psychiatry and neurology based on my own experience as an educator, practitioner
      and scholar of both disciplines. It is not, therefore, a piece of research work
      in the usual sense of the word. Such has been my commitment to Revista de
      Neurologia that I was asked to analyse the current situation of neurology and
      psychiatry and the possible relations between them, and the editors have accepted
      this way of studying the matter.

PMID- 18075992
TI  - [Weber's syndrome in a child following surgery to correct displacement of a
      catheter].

PMID- 18075991
TI  - [Peculiarities of meningoencephalitis caused by Angiostrongylus cantonensis in
      America].
AB  - INTRODUCTION: 25 years ago was first reported in Cuba and in the western
      hemisphere an emergent disease: eosinophilic meningoencephalitis due to
      Angiostrongylus cantonensis larvae. AIM: To collect in a summary form the
      accumulated experience and the findings of the study of this parasitosis during
      the period in the Western hemisphere. DEVELOPMENT AND CONCLUSIONS: There have
      been collected the first evidences, the parasitological and malacological
      findings, the experimental and molecular studies on immunology and
      neuroimmunology, the clinic-pathological findings in children and adults with the
      particularities of this diseases in our environment with special emphasis in the
      never-before scientific findings reported. It has been documented the testimony,
      the main findings among the malacological studies, the role of the immunoglobulin
      E and the mechanism involved in the central nervous system, the intrathecal
      synthesis patterns of immunoglobulins and the clinical elements in children and
      adults.

PMID- 18075993
TI  - [Complex partial seizures secondary to a low-grade lipoastrocytoma].

PMID- 18075994
TI  - [Prevalence of periodic limb movement disorder in infancy].

PMID- 18075996
TI  - The road from The Microbial world to Microbe.
AB  - The year 2007 commemorates the 50th anniversary of the publication of The
      Microbial World, the seminal microbiology textbook that shattered the
      microbiology world and whose first edition was coauthored by Roger Y. Stanier,
      Michael Doudoroff and Edward A. Adelberg. The year 2007 marks also twenty-five
      years of Stanier's passing away. The Spanish Society for Microbiology (SEM) with
      the support of Fundacion Ramon Areces has organized a Symposium, in the frame of
      the 21st national congress of the SEM (Seville, 17-20 September 2007), to
      commemorate those anniversaries, and has invited us (Schaechter, Ingraham and
      Neidhardt) to contribute to this celebration.

PMID- 18075997
TI  - The hidden side of the prokaryotic cell: rediscovering the microbial world.
AB  - How many different forms of life exist and how they are evolutionarily related is
      one of the most challenging problems in biology. In 1962, Roger Y. Stanier and
      Cornelis B. van Niel proposed "the concept of a bacterium" and thus allowed
      (micro)biologists to divide living organisms into two primary groups: prokaryotes
      and eukaryotes. Initially, prokaryotes were believed to be devoid of any internal
      organization or other characteristics typical of eukaryotes, due to their minute
      size and deceptively simple appearance. However, the last few decades have
      demonstrated that the structure and function of the prokaryotic cell are much
      more intricate than initially thought. We will discuss here two characteristics
      of prokaryotic cells that were not known to Stanier and van Niel but which now
      allow us to understand the basis of many characteristics that are fully developed
      in eukaryotic cells: First, it has recently become clear that bacteria contain
      all of the cytoskeletal elements present in eukaryotic cells, demonstrating that
      the cytoskeleton was not a eukaryotic invention; on the contrary, it evolved
      early in evolution. Essential processes of the prokaryotic cell, such as the
      maintenance of cell shape, DNA segregation, and cell division, rely on the
      cytoskeleton. Second, the accumulation of intracellular storage polymers, such as
      polyhydroxyalkanoates (a property studied in detail by Stanier and colleagues),
      provides a clear evolutionary advantage to bacteria. These compounds act as a
      "time-binding" mechanism, one of several prokaryotic strategies to increases
      survival in the Earth's everchanging environments.

PMID- 18075998
TI  - A pyrF auxotrophic mutant of Sinorhizobium fredii HH103 impaired in its symbiotic
      interactions with soybean and other legumes.
AB  - Transposon Tn5-Mob mutagenesis allowed the selection of a Sinorhizobium fredii
      HH103 mutant derivative (SVQ 292) that requires the presence of uracil to grow in
      minimal media. The mutated gene, pyrF, codes for an orotidine-5 - monophosphate
      decarboxylase (EC 4.1.1.23). Mutant SVQ 292 and its parental prototrophic mutant
      HH103 showed similar Nod-factor and lipopolysaccharide profiles. The symbiotic
      properties of mutant SVQ 292 were severely impaired with all legumes tested.
      Mutant SVQ 292 formed small ineffective nodules on Cajanus cajan and abnormal
      nodules (pseudonodules) unable to fix nitrogen on Glycine max (soybean),
      Macroptitlium atropurpureum, Indigofera tinctoria, and Desmodium canadense. It
      also did not induce any macroscopic response in Macrotyloma axillare roots. The
      symbiotic capacity of SVQ 292 with soybean was not enhanced by the addition of
      uracil to the plant nutritive solution.

PMID- 18075999
TI  - Influence of nutrients on enhancing laccase production by Botryosphaeria rhodina
      MAMB-05.
AB  - The physiological requirements needed to enhance the production of laccases by
      the ascomycete Botryosphaeria rhodina MAMB-05 in submerged cultivation were
      examined under non-induced and induced (veratryl alcohol, VA) conditions. Under
      non-induced conditions (-VA), the initial pH, C:N ratio, and inorganic N source
      did not influence laccase production, in contrast to Tween 80, soybean oil, and
      copper, which significantly increased laccase production, and proline and urea,
      which suppressed laccase formation. In addition, Tween 60 could serve as the sole
      carbon source for the production of these enzymes. Under VA-induced conditions of
      fungal growth, factors such as inoculum type, time-point of addition of inducer,
      initial pH, C:N ratio, and type of N source, influenced the production of
      laccases; however, unlike the non-induced conditions, proline and urea did not
      act as suppressors. Each of these physiological conditions exerted different
      effects on biomass production. The nutritional conditions examined for B. rhodina
      MAMB-05 are discussed in relation to their influence on fungal growth and laccase
      production.

PMID- 18076000
TI  - Culture conditions for zinc- and pH-regulated gene expression studies in
      Aspergillus fumigatus.
AB  - In Aspergillus fumigatus, the regulation of zinc homeostasis is strongly
      influenced by environmental pH. Thus, the study of zinc-regulated gene expression
      in A. fumigatus requires controlling variations in culture pH, as this may affect
      zinc availability. However, depending on the nitrogen source, the pH of the
      culture can change dramatically over time. In addition, due to the ubiquitous
      distribution of zinc and that it is an essential micronutrient required in minute
      amounts for optimal fungal growth, neither buffering of the culture media to
      prevent pH variations nor the use of chelating agents is advisable if mycelium is
      to be used for expression analyses. In this work, the growth of A. fumigatus in
      several culture media was examined in order to determine the conditions yielding
      mycelia suitable for gene expression analyses in acid and neutral media,
      regardless of zinc availability. Our results showed that a zinc-limiting
      synthetic basal medium could be readily converted into a zinc-replete one and
      subsequently into acid or neutral medium by using, respectively, ammonium or
      nitrate as nitrogen source.

PMID- 18076001
TI  - Co-occurrence of viral and bacterial pathogens in disease outbreaks affecting
      newly cultured sparid fish.
AB  - Several microbial disease outbreaks in farm stocks of newly cultured sparid fish
      species, such as common seabream, redbanded seabream, and white seabream, were
      recorded from 2004 to 2006. This study describes the isolation and
      characterization of the potential causative agents, either bacteria or viruses,
      of these outbreaks. The isolated bacterial strains were characterized according
      to traditional taxonomical analyses and sequencing of a 16S rDNA fragment. Most
      bacteria were identified as Vibrio spp. and Photobacterium damselae subsp.
      damselae. The development of cytopathic effects (CPE) on different fish cell
      lines, the application of specific nested-PCR tests for infectious pancreatic
      necrosis virus (IPNV), viral nervous necrosis virus (VNNV) and viral hemorrhagic
      septicemia virus (VHSV), and subsequent sequence analyses were used for virus
      detection and identification. VNNV, related to the striped jack neural necrosis
      virus (SJNNV) genotype, and VHSV, related to the genotype Ia, were the only
      viruses detected. VNNV was isolated from the three fish species under study in
      five different outbreaks, whereas VHSV was isolated from common seabream and
      white seabream during two of these outbreaks. IPNV was not detected in any case.

PMID- 18076002
TI  - Identification of signature proteins that are distinctive of the Deinococcus
      Thermus phylum.
AB  - The members of the Deinococcus-Thermus phylum, which include many species that
      are resistant to extreme radiation, as well as several thermophiles, have been
      recognized solely on the basis of their branching patterns in 16S rRNA and other
      phylogenetic trees. No biochemical or physiological characteristic is currently
      known that is unique to this group of species. To identify genes/proteins that
      are exclusive of this group of species, systematic protein basic local alignment
      tool (Blastp) searches were carried out on each open reading frame (ORF) in the
      genome of Deinococcus radiodurans. These studies identified 65 proteins that were
      only found in all three sequenced Deinococcus-Thermus genomes (viz. D.
      radiodurans, D. geothermalis and Thermus thermophilus), but not in any other
      bacteria. In addition, these studies also identified 206 proteins that are
      exclusively found in the two Deinocococci species, and 399 proteins that are
      unique to D. radiodurans. The identified proteins, which represent a genetic
      repertoire distinctive to the Deinococcus-Thermus group, or to Deinococci
      species, provide novel molecular markers for their identification and
      characterization. The cellular functions of most of these proteins are not known
      and their studies should prove useful in identifying novel biochemical and
      physiological characteristics that are exclusive of these groups of bacteria and
      also those responsible for the extreme radiation resistance of Deinococci.

PMID- 18076003
TI  - Analysis of s-triazine-degrading microbial communities in soils using most
      probable-number enumeration and tetrazolium-salt detection.
AB  - A simple and sensitive method for the detection and enumeration of microbial s
      triazine-degrading microorganisms in soil was designed. The procedure is based on
      the ability of some microbes to use s-triazines, such as simazine, atrazine, and
      cyanuric acid, as sole nitrogen source. It employs the respiration indicator
      2,3,5-triphenyl-2H-tetrazolium chloride (TTC) to detect metabolic activity and
      the most-probable-number (MPN) enumeration in microtiter plates. The method was
      used to identify simazine- and cyanuric acid-degrading activities in agricultural
      soils treated with the herbicide simazine. The MPN-TTC method showed that the
      number of simazine- and cyanuric acid-degrading microorganisms increased four
      weeks after the herbicide simazine had been applied.

PMID- 18076004
TI  - Microbiology: a dangerous profession?
AB  - The history of science contains many cases of researchers who have died because
      of their professional activity. In the field of microbiology, some have died or
      have come close to death from infection by agents that were the subject of their
      research (Table 1). Infections that had a lethal outcome were usually accidental.
      Sometimes, however, researchers inoculated themselves with the pathogen or did
      not take preventive measures against the potential pathogen because they wanted
      to prove their hypotheses--or disprove someone else's--regarding the origin of
      the infection. Here is an overview of several episodes in the history of
      microbiology since the mid nineteenth century involving researchers or workers in
      fields related to microbiology who have become infected. They are considered here
      in their historical context to provide insights into some of the pillars of
      modern microbiology--The giants on whose shoulders several generations of
      microbiologists have stood to see further.

PMID- 18076005
TI  - The role of permanent and transitory shocks in explaining international health
      expenditures.
AB  - While there is a growing literature that examines the issue of cointegration (co
      movement over the long run) among health expenditures, there are no studies that
      examine the issue of common cycles (co-movement over the short run) among health
      expenditures. We undertake a multivariate variance decomposition analysis of per
      capita health expenditures of the USA, the UK, Japan, Canada, and Switzerland
      based on a common-trend-common-cycle restriction framework, to examine the
      relative importance of permanent and transitory innovations in explaining
      variations in per capita health expenditures in each of the five countries. Our
      main finding is that transitory shocks are more important in explaining per
      capita health expenditures in the UK, Japan, and Switzerland, while permanent
      shocks dominate variations in per capita health expenditures in the USA and
      Canada over short horizons.

PMID- 18076006
TI  - Chemistry and biology of the aeruginosin family of serine protease inhibitors.
AB  - The aeruginosins have been isolated from marine sponges and cyanobacterial
      waterblooms, sources that are phylogenetically distinct and the bodies of water
      are geographically well-separated. The aeruginosins comprise a central hydroxy-
      (or dihydroxy-) octahydroindole carboxamide core unit, onto which are appended
      unusual amino acids on the carboxy and amino termini as part of the linear
      peptide array. Potent inhibitory activity of serine proteases in vitro is
      exhibited by some of the aeruginosins as a result of the presence and proper
      deployment of three important pharmacophoric subunits: a P1 arginine mimetic, and
      two hydrophobic residues with interaction sites designated as P2 and P3. In this
      article, we provide the first comprehensive review on the chemistry and biology
      of the aeruginosins, with an emphasis on their sources, structural revisions, and
      total syntheses.

PMID- 18076007
TI  - Metal-tunable nanocages as artificial chemosensors.

PMID- 18076008
TI  - Clostridium neurotoxin fragments as potential targeting moieties for liposomal
      gene delivery to the CNS.
AB  - Targeted transfection of the CNS with synthetic, nonviral vectors represents a
      huge technical challenge. The approach explored here attempts to combine self
      assembly ABCD nanoparticles (Kostarelos and Miller, Chem. Soc. Rev. 2005, 34,
      970), with the potential of Clostridium neurotoxin fragments to effect receptor
      mediated transfection of neuronal cells. Cationic liposome-plasmid DNA complexes
      were first modified with a PEG stealth layer, before the addition of C-terminal
      fragments of tetanus toxin (TH(C)), botulinum toxin (BH(C)) or the truncated C
      terminal domain of TH(C) as biological "targeting" ligands. First-generation
      nanoparticles were identified for the transfection of two neuronal cell lines
      (human SH-5YSY and rat/mouse hybrid N18-RE105); control studies were also
      performed with HeLa cells. ABCD nanoparticle transfections of the neuronal cell
      lines were up to 30-fold higher than corresponding control transfections with
      nanoparticles that lacked the protein ligand. We also demonstrate apparent
      receptor-mediated uptake by means of competition-binding and real-time confocal
      experiments. By contrast, nanoparticle transfection of HeLa cells appeared to
      involve alternative nonspecific enhanced cellular uptake mechanism(s). Receptor
      mediated and nonspecific mechanisms appear to be in competition, potentially
      harming the capacity of receptor-mediated delivery to effect proper targeted
      delivery of nucleic acids to cells ex vivo and in vivo.

PMID- 18076010
TI  - Gold-enhanced low-temperature oxidation of silicon nanowires.

PMID- 18076009
TI  - Zinc(II) coordination complexes as membrane-active fluorescent probes and
      antibiotics.
AB  - Molecular probes with zinc(II)-(2,2'-dipicolylamine) coordination complexes
      associate with oxyanions in aqueous solution and target biomembranes that contain
      anionic phospholipids. This study examines a new series of coordination complexes
      with 2,6-bis(zinc(II)-dipicolylamine)phenoxide as the molecular recognition unit.
      Two lipophilic analogues are observed to partition into the membranes of
      zwitterionic and anionic vesicles and induce the transport of phospholipids and
      hydrophilic anions (carboxyfluorescein). These lipophilic zinc complexes are
      moderately toxic to mammalian cells. A more hydrophilic analogue does not exhibit
      mammalian cell toxicity (LD(50) >50 microg mL(-1)), but it is highly active
      against the Gram-positive bacteria Staphylococcus aureus (MIC of 1 microg mL(
      1)). Furthermore, it is active against clinically important S. aureus strains
      that are resistant to various antibiotics, including vancomycin and oxacillin.
      The antibiotic action is attributed to its ability to depolarize the bacterial
      cell membrane. The intense bacterial staining that was exhibited by a fluorescent
      conjugate suggests that this family of zinc coordination complexes can be used as
      molecular probes for the detection and imaging of bacteria.

PMID- 18076011
TI  - Gastroesophageal reflux disease (GERD): is there more to the story?
AB  - Gastroesophageal reflux disease (GERD) affects both men and women worldwide, with
      the most common symptom of GERD being frequent heartburn. If left untreated, more
      serious diseases including esophagitis and/or esophageal cancer may result. GERD
      has been commonly held to be the result of gastric acid refluxing into the
      esophagus. Recent work, however, has shown that there are acid-producing cells in
      the upper aerodigestive tract. In addition, acid-producing bacteria located
      within the upper gastrointestinal tract and oral cavity may also be a
      contributing factor in the onset of GERD. Proton pump inhibitors (PPIs) are
      commonly prescribed for treating GERD; these drugs are designed to stop the
      production of gastric acid by shutting down the H(+)/K(+)-ATPase enzyme located
      in parietal cells. PPI treatment is systemic and therefore significantly
      different than traditional antacids. Although a popular treatment choice, PPIs
      exhibit substantial interpatient variability and commonly fail to provide a
      complete cure to the disease. Recent studies have shown that H(+)/K(+)-ATPases
      are expressed in tissues outside the stomach, and the effects of PPIs in these
      nongastric tissues have not been fully explored. Likewise, acid-producing
      bacteria containing proton pumps are present in both the oral cavity and
      esophagus, and PPI use may also adversely affect these bacteria. The use of PPI
      therapy is further complicated by the two philosophical approaches to treating
      this disease: to treat only symptoms or to treat continuously. The latter
      approach frequently results in unwanted side effects which may be due to the PPIs
      acting on nongastric tissues or the microbes which colonize the upper
      aerodigestive tract.

PMID- 18076012
TI  - Association between standard clinical and pathologic characteristics and the 21
      gene recurrence score in breast cancer patients: a population-based study.
AB  - BACKGROUND: The 21-gene recurrence score (RS) assay has been reported to
      accurately predict the risk of disease recurrence and chemotherapy benefit in
      women with estrogen receptor (ER)-positive, lymph node (LN)-negative breast
      cancer who are treated with tamoxifen. To the authors' knowledge, the association
      between the RS and clinicopathologic characteristics has been studied in
      randomized and case-control trials, but not in the general population. METHODS:
      The authors analyzed the correlation between clinicopathologic breast cancer
      characteristics and RS among 300 consecutive Israeli patients who were referred
      to undergo the test between October 2004 and October 2006. RESULTS: Low,
      intermediate, and high RS were noted in 109 patients (36%), 134 patients (45%),
      and 57 patients (19%), respectively. The median age of the patients was 54 years
      and the median tumor size was 1.6 cm. High tumor grade, low progesterone receptor
      expression, infiltrating ductal histology, and high HER-2 expression were found
      to be associated with a high RS, whereas patient age, tumor size, ER expression,
      and lymph node micrometastasis were found to correlate poorly with the RS. The
      ability of any of these variables, either alone or in combination, to predict the
      RS was limited. Similarly, neither commonly used guidelines nor the Adjuvant!
      Online software were found to be able to predict the RS. CONCLUSIONS: The results
      of the current study suggest that neither standard clinicopathologic features nor
      commonly used assessment tools can reliably predict the RS among referred breast
      cancer patients compared with a clinical trial population. These data also may
      indicate the need for additional studies regarding the role of the RS among
      certain subsets of breast cancer patients, including those with noninfiltrating
      ductal carcinoma histology and the presence of lymph node micrometastasis.

PMID- 18076013
TI  - Multimarker phenotype predicts adverse survival in patients with lymph node
      negative colorectal cancer.
AB  - BACKGROUND: The heterogeneity of stage II colon cancer underlines the need for
      identifying high-risk, lymph node-negative patients. The objective of this study
      was to define a multimarker prognostic model of 5-year survival in patients with
      lymph node-negative, mismatch repair (MMR)-proficient colorectal cancer (CRC).
      METHODS: Immunohistochemistry for 13 tumor markers was performed on 587 lymph
      node-negative, MMR-proficient CRC samples by using a tissue microarray.
      Immunoreactivity was evaluated semiquantitatively. A receiver-operating
      characteristic-based approach was used to detect clinically relevant tumor
      markers and to determine cutoff scores for tumor positivity. Univariate and
      multivariate analyses stratified by pathologic T3 (pT3) or pT4 tumor
      classification were performed. RESULTS: In univariate analysis, the absence of
      CD8+ tumor infiltrating lymphocytes (TILs) (P < .001), loss of p27 (P = .006),
      positive urokinase-type plasminogen activator (uPA) expression (P = .002), and
      positive uPA receptor (uPAR) expression (P = .037) were associated with an
      adverse prognosis. In multivariate analysis, CD8 (P = .001), p27 (P = .031), and
      uPA (P = .014) were independent prognostic factors. The multimarker phenotype of
      negative CD8, loss of p27, and positive uPA expression led to significantly worse
      survival compared with all other combinations of these features. Stratified by
      pT3 or pT4 stage, CD8 (P = .006) and uPA (P = .011) had independent prognostic
      value. Combined CD8 negativity and uPA positivity led to a more adverse prognosis
      in both patients with pT3 tumors and patients with pT4 tumors (P < .001). No
      difference was observed in the length of survival between patients with pT3
      tumors who had CD8 negativity and uPA positivity and patients with pT4 tumors (P
      = .267). CONCLUSIONS: The multimarker phenotype of the absence of CD8+ TILs, loss
      of p27, and positive uPA expression was predictive of an adverse prognosis in
      patients with lymph node-negative, MMR-proficient CRC. The current findings
      suggested that a subgroup of patients with high-risk, lymph node-negative pT3
      tumors should be considered for adjuvant therapy.

PMID- 18076014
TI  - Adjuvant radiotherapy improves overall survival for patients with lymph node
      positive head and neck squamous cell carcinoma.
AB  - BACKGROUND: Although adjuvant radiotherapy (RT) is often recommended for locally
      advanced squamous cell carcinoma of the head and neck (HNSCC), its effect on
      overall or cancer-specific survival has not been clearly demonstrated. In the
      current study, the frequency and effect of adjuvant RT on overall survival was
      investigated in patients with resected lymph node-positive head and neck cancer.
      METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database,
      patients were selected with lymph node-positive HNSCC (American Joint Committee
      on Cancer and SEER stage 3/4) who were treated either with surgery alone or
      surgery and RT and were diagnosed between 1988 and 2001. A total of 8795 patients
      who met the inclusion criteria for analysis comprised the study population, with
      a median follow-up of 4.3 years for patients still alive at the time of last
      follow-up. RESULTS: Adjuvant RT was utilized in 84% of patients. Adjuvant RT
      improved the 5-year overall survival (43.2% [95% confidence interval (95% CI),
      41.9-44.4%] for surgery + RT vs 33.4% [95% CI, 30.7-36.0%] for surgery alone; P <
      .001) and cancer-specific survival (50.9% for surgery + RT vs 42.1% for surgery)
      on univariate analysis. On multivariate analysis, adjuvant RT (hazards ratio [HR]
      of 0.78; 95% CI, 0.71-0.86 [P < .001]) remained a significant predictor of
      improved survival. The significant benefit of radiation on overall survival was
      noted for lymph node-positive patients with both primary tumors localized to the
      involved organ (HR of 0.81; 95% CI, 0.71-0.94 [P = .007]) and more locally
      invasive primary tumors (HR of 0.77; 95% CI, 0.68-0.87 [P < .001]). CONCLUSIONS:
      In what to the authors' knowledge is the largest reported analysis of adjuvant RT
      in patients with locally advanced HNSCC published to date, adjuvant RT resulted
      in an approximately 10% absolute increase in 5-year cancer-specific survival and
      overall survival for patients with lymph node-positive HNSCC compared with
      surgery alone. Despite combined surgery and adjuvant RT, outcomes in this high
      risk population remain suboptimal, emphasizing the need for continued
      investigation of innovative treatment approaches.

PMID- 18076015
TI  - Tumor mitotic rate, size, and location independently predict recurrence after
      resection of primary gastrointestinal stromal tumor (GIST).
AB  - BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most frequent sarcoma of
      the intestinal tract and often shows constitutive activation of either the KIT or
      PDGFRA receptor tyrosine kinases because of gain-of-function mutation. Although
      the efficacy of tyrosine kinase inhibitors in metastatic GIST depends on tumor
      mutation status, there have been conflicting reports on the prognostic importance
      of KIT mutation in primary GIST. METHODS: A total of 127 patients were studied
      who presented to our institution from 1983 to 2002 with localized primary GIST
      and underwent complete gross surgical resection of disease. The majority of
      tumors originated in the stomach (58%) or small intestine (28%). By using
      polymerase chain reaction (PCR) and direct sequencing, a KIT mutation was found
      in 71% of patients and a PDGFRA mutation in 6%. RESULTS: After a median follow-up
      of 4.7 years, recurrence-free survival was 83%, 75%, and 63% at 1, 2, and 5
      years, respectively. On multivariate analysis recurrence was predicted by > or =5
      mitoses/50 high-power fields, tumor size > or =10 cm, and tumor location (with
      patients having small bowel GIST doing the worst). In particular, a high mitotic
      rate conferred a hazard rate of 14.6 (95% confidence interval, 6.5-32.4).
      Specific KIT mutations had prognostic importance by univariate but not
      multivariate analysis. Patients with KIT exon 11 point mutations and insertions
      had a favorable prognosis. Those with KIT exon 9 mutations or KIT exon 11
      deletions involving amino acid W557 and/or K558 had a higher rate of recurrence,
      whereas patients without a tyrosine kinase mutation had intermediate outcome.
      CONCLUSIONS: In the absence of therapy with tyrosine kinase inhibitors,
      recurrence in completely resected primary GIST is independently predicted by
      mitotic rate, tumor size, and tumor location.

PMID- 18076017
TI  - Readability in the British Journal of Surgery.
AB  - BACKGROUND: Readability scores predict the ease with which a document can be read
      and understood. Identification of the factors that affect readability might
      improve the quality of surgical literature. METHODS: Electronic copies of
      submitted, peer reviewed and edited manuscripts of 189 articles published in the
      British Journal of Surgery from March 2006 to April 2007 were studied. Flesch
      reading ease scores were calculated for each version. Type of article (meta
      analysis, review, randomized trial or other original paper), first language of
      principal author, number of peer revisions and editor were recorded. RESULTS:
      Flesch score varied according to type of article (P = 0.004). The mean
      readability score was lower when English was the first language of the principal
      author (P = 0.016). There was no significant difference in mean Flesch score
      between the submitted and accepted (peer reviewed) manuscripts, but a significant
      increase occurred after editing (P < 0.001), which did not vary between editors.
      CONCLUSION: Several factors influence readability. Knowledge of such factors
      might help authors to improve their scientific writing.

PMID- 18076018
TI  - Randomized clinical trial of laparoscopic total (Nissen) versus posterior partial
      (Toupet) fundoplication for gastro-oesophageal reflux disease based on
      preoperative oesophageal manometry.
AB  - BACKGROUND: Laparoscopic fundoplication is an accepted treatment for symptomatic
      gastro-oesophageal reflux disease. The aim of this study was to clarify whether
      total (Nissen) or partial (Toupet) fundoplication is preferable, and whether
      preoperative oesophageal manometry should be used to determine the degree of
      fundoplication performed. METHODS: Preoperative oesophageal manometry was used to
      stratify 127 patients with established gastro-oesophageal reflux disease into
      effective (75) and ineffective (52) oesophageal motility groups. Patients in each
      group were randomized to Nissen (64) or Toupet (63) fundoplication. RESULTS: No
      significant differences between the operative groups were seen in heartburn,
      regurgitation or other reflux-related symptoms up to 1 year after surgery.
      Dysphagia of any degree (27 versus 9 per cent; P = 0.018) and chest pain on
      eating (22 versus 5 per cent; P = 0.018) were more prevalent at 1 year in the
      Nissen group. There were no differences in postoperative symptoms between the
      effective and ineffective motility groups. Surgery failed in eight patients on
      postoperative pH criteria, three in the Nissen group and five in the Toupet
      group. CONCLUSION: Any differences in the symptomatic outcome of laparoscopic
      Nissen and Toupet fundoplication appear minimal. There is no reason to tailor the
      degree of fundoplication to preoperative oesophageal manometry.

PMID- 18076019
TI  - Laparoscopic peritoneal lavage for generalized peritonitis due to perforated
      diverticulitis.
AB  - BACKGROUND: The standard approach to generalized peritonitis due to perforated
      diverticulitis involves open surgery and diversion of faecal content. This study
      assessed the feasibility of laparoscopic peritoneal lavage. METHODS: A
      prospective multi-institutional study of 100 patients was undertaken. All
      consenting patients with perforated diverticulitis causing generalized
      peritonitis underwent attempted laparoscopic peritoneal lavage. The degree of
      peritonitis, according to the Hinchey grading system, was recorded. Primary
      endpoints were operative success and resolution of symptoms. RESULTS: Patients
      had a median age of 62.5 (range 39-94) years, a male : female ratio of 2 : 1 and
      a median American Society of Anesthesiologists grade of III (range II-V). Eight
      patients with grade 4 diverticulitis had conversion to an open Hartmann's
      procedure. The remaining 92 patients were managed by laparoscopic lavage, with
      morbidity and mortality rates of 4 and 3 per cent respectively. Two patients
      required postoperative intervention for a pelvic abscess. Only two patients re
      presented with diverticulitis at a median follow up of 36 (range 12-84) months.
      CONCLUSION: Laparoscopic management of perforated diverticulitis with generalized
      peritonitis is feasible, with a low recurrence risk in the short term.

PMID- 18076020
TI  - Genetic susceptibility in pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: The strongest risk factors for pancreatic adenocarcinoma are tobacco
      smoking and increasing age. However, only a few smokers or elderly individuals
      develop the disease and genetic factors are also likely to be important. METHODS:
      The literature on genetic factors modifying susceptibility to cancer was
      reviewed, with particular regard to the interindividual variation that exists in
      the development of pancreatic adenocarcinoma. RESULTS: Tobacco-derived carcinogen
      metabolizing enzyme gene variants have been the main area of study in stratifying
      the risk of sporadic pancreatic cancer. Inconsistent results have emerged from
      the few molecular epidemiological studies performed. CONCLUSION: There is great
      scope for further investigation of critical pathways and unidentified genetic
      influences may be revealed. This may eventually allow the identification of
      individuals at high risk who might be targeted for screening.

PMID- 18076021
TI  - Tissue expression and enzymologic characterization of human prostate specific
      membrane antigen and its rat and pig orthologs.
AB  - BACKGROUND: Prostate specific membrane antigen (PSMA), also called glutamate
      carboxypeptidase II (GCPII), is a target enzyme for diagnosis and treatment of
      prostate cancer. Moreover, it is upregulated in the vasculature of most solid
      tumors and is therefore a potential target for the generation of novel
      antineoplastics. In this context, we analyze the possibility of using rat and pig
      as animal models for enzymologic and in vivo studies. METHODS: We prepared the
      recombinant extracellular part of human, rat, and pig GCPII in S2 cell media and
      characterized the activity and inhibition profiles of the three orthologs by
      radioenzymatic assay. We performed Western blot analysis of GCPII expression in
      human, rat, and pig tissues using the monoclonal antibody GCP-04 and confirmed
      these findings by activity measurements and immunohistochemistry. RESULTS: The
      three recombinant proteins show similar specific enzymatic activities and
      inhibition profiles. Tissue expression analysis revealed that most of the pig and
      human tissues show at least some GCPII-positivity, while the expression pattern
      in rat is more restricted. Moreover, tissues such as prostate and testes exhibit
      different GCPII expression levels among the species studied. CONCLUSIONS: The rat
      and pig orthologs of GCPII seem to be suitable to approximate human GCPII in
      enzymologic studies. However, the diffuse expression pattern of GCPII in animal
      and human tissues could be a caveat for the potential utilization of GCPII
      targeted anticancer drugs. Furthermore, variations in GCPII tissue distribution
      among the species studied should be considered when using rat or pig as models
      for antineoplastic drug discovery.

PMID- 18076022
TI  - Proteasome inhibition blocks caspase-8 degradation and sensitizes prostate cancer
      cells to death receptor-mediated apoptosis.
AB  - BACKGROUND: Proteasome inhibition through the administration of Velcade is a
      viable chemotherapeutic strategy that is approved to treat multiple myeloma and
      is being evaluated for efficacy against prostate cancer. Currently, the apoptotic
      pathways that contribute to this anticancer response are poorly understood. Our
      goal is to test the extent to which proteasome inhibition modulates apoptosis
      through death receptor pathways. METHODS: Several prostate cancer cell lines and
      primary prostate epithelial cells (PrECs) were used as models. The death receptor
      pathway was activated by the expression of Fas ligand (FasL) or addition of TNF
      related apoptosis-inducing ligand (TRAIL) in the presence or absence of
      proteasome inhibitors. The apoptotic response was quantified by annexin V, TUNEL
      and nuclear condensation assays. Western blot analysis was conducted to quantify
      protein levels and enzyme assays were used to measure caspase activity. RESULTS:
      Proteasome inhibition markedly sensitized prostate cancer cells to apoptosis
      initiated by Fas ligand (FasL) or TRAIL. In the presence of either death ligand,
      procaspase-8 processing occurred, but led to minimal amounts of active caspase-8.
      The addition of Velcade, however, led to robust active caspase-8 protein
      abundance and activity. In the presence of Velcade the caspase-8 p18 subunit half
      life increased from 22 min to over 2 hr. CONCLUSIONS: These findings demonstrate
      that proteasome inhibition can sensitize cells to apoptosis elicited by tumor
      necrosis factor ligands and retarding caspase-8 degradation provides one
      explanation for this activity. This study suggests that the clinical efficacy of
      Velcade may result, at least in part, from the activity of death ligands.

PMID- 18076023
TI  - Altered expression of genes regulating angiogenesis in experimental androgen
      independent prostate cancer.
AB  - BACKGROUND: The aim of this study was to investigate how the expression of genes
      regulating angiogenesis is altered when prostate cancer cells progress into
      androgen-independency. METHODS: A gene array specific for angiogenesis was used
      to compare the human prostate cancer cell line LNCaP (androgen-dependent) with
      its more angiogenic and tumorigenic subline LNCaP-19 (androgen-independent).
      Results were verified with real-time RT-PCR, and further investigations were
      focused on the angiogenesis inhibitor a disintegrin and metalloproteinase with
      thrombospondin motifs 1 (ADAMTS1). Expression of ADAMTS1 was investigated in
      vitro as well as in subcutaneous tumors with real-time RT-PCR and Western
      blotting. Microvessel density (MVD), versican proteolysis and protein levels of
      TIMP-2 and TIMP-3, known as ADAMTS1 inhibitors, were also analyzed in tumor
      xenografts. RESULTS: The gene array revealed decreased expression of ADAMTS1,
      ephrin-A5, fibronectin 1, and neuropilin 1 in LNCaP-19 compared to LNCaP, while
      expression of midkine and VEGF were increased. Further studies showed that mRNA
      and protein levels of ADAMTS1 were significantly lower in LNCaP-19 compared to
      LNCaP, both in vitro and in subcutaneous tumors. The amount of ADAMTS1 correlated
      negatively with MVD, but no relation was found between ADAMTS1 and versican
      proteolysis. CONCLUSIONS: Expression of several genes associated with
      angiogenesis was altered during transition into androgen-independency. Among
      these, a significant decrease was found for ADAMTS1, whose expression inversely
      correlated with MVD. Its role in progression of prostate cancer needs further
      investigation, but this inhibitor of angiogenesis could be an interesting
      candidate for future anti-angiogenic therapy.

PMID- 18076024
TI  - The association of prostate stem cell antigen (PSCA) mRNA expression and
      subsequent prostate cancer risk in men with benign prostatic hyperplasia
      following transurethral resection of the prostate.
AB  - BACKGROUND: Prior data showed prostate stem cell antigen (PSCA) mRNA expression
      in benign prostatic hyperplasia (BPH) tissues. The purpose of the present
      investigation was to determine whether PSCA mRNA expression in resected BPH
      samples was associated with the subsequent presence of cancer following
      transurethral resection of the prostate (TURP). METHODS: PSCA in situ
      hybridization was performed on the TURP-resected tissues from 288 patients, who
      were histopathologically confirmed BPH without cancer. All these patients were
      continuously followed for 9-70 months postoperatively. Univariate and
      multivariate cox regression analyses were used to evaluate the predictive
      performance of PSCA mRNA for subsequent cancer onset following TURP. RESULTS:
      PSCA mRNA was detected in 93/288 (32.3%) of the resected BPH specimens, with a
      mean positive-labeling cells of 23.8%, in which 22 patients (23.7%) were
      identified as having PCa on follow-up. Of 195 patients with negative expression
      for PSCA mRNA 2 (1.0%) were subsequently found with PCa. PSCA mRNA expression
      levels were directly proportional to higher Gleason score and clinical T stage.
      Univariate and multivariate cox regression analyses demonstrated that only PSCA
      mRNA expression was predictive of the subsequent cancer development after TURP,
      however, PSA velocity was an univariately significant but not multivariately
      significant predictor. CONCLUSIONS: This prospective study identifies PSCA mRNA
      in BPH as a significant predictor of cancer development after TURP, suggesting
      that PSCA may be used to identify patients who are at high risk for subsequent
      cancer onset following TURP for BPH and the PSCA test may be useful when applied
      for repeat biopsies.

PMID- 18076025
TI  - Computational prediction of the binding site of proteinase 3 to the plasma
      membrane.
AB  - Proteinase 3 (PR3) is a neutrophil-derived serine proteinase localized within
      cytoplasmic granules which can be released upon activation. PR3 is exposed at the
      neutrophil plasma membrane where it can mediate proinflammatory effects.
      Moreover, PR3 membrane expression is of special relevance in patients with
      Wegener's granulomatosis, a systemic vasculitis presenting anticytoplasmic
      neutrophil autoantibodies (ANCA) against PR3, which can bind to PR3 expressed at
      the surface of neutrophils and amplify their activation state. Therefore, it is
      of special relevance to unravel the molecular mechanisms governing its
      association with the membrane to be able to modulate it. To this end, we
      performed molecular dynamics (MD) simulations of PR3 with the implicit membrane
      model IMM1-GC to identify its interfacial binding site (IBS). Both the energies
      and structures resulting from the MD suggest that PR3 associates strongly with
      anionic membranes. We observe a unique IBS consisting of five basic (R177, R186A,
      R186B, K187, R222) and six hydrophobic (F165, F166, F224, L223, F184, W218) amino
      acids. The basic residues provide the driving force to orient PR3 at the membrane
      surface, so that the hydrophobic residues can anchor into the hydrocarbon region.
      Energy decomposition and in silico mutations show that only a few residues
      account for the membrane association. Similar calculations with HNE suggest a
      different membrane-binding mechanism. Our results agree with previous
      experimental observations and this work predicts, for the first time, the
      structural determinants of the binding of PR3 to membranes.

PMID- 18076026
TI  - Protein classification with imbalanced data.
AB  - Generally, protein classification is a multi-class classification problem and can
      be reduced to a set of binary classification problems, where one classifier is
      designed for each class. The proteins in one class are seen as positive examples
      while those outside the class are seen as negative examples. However, the
      imbalanced problem will arise in this case because the number of proteins in one
      class is usually much smaller than that of the proteins outside the class. As a
      result, the imbalanced data cause classifiers to tend to overfit and to perform
      poorly in particular on the minority class. This article presents a new technique
      for protein classification with imbalanced data. First, we propose a new
      algorithm to overcome the imbalanced problem in protein classification with a new
      sampling technique and a committee of classifiers. Then, classifiers trained in
      different feature spaces are combined together to further improve the accuracy of
      protein classification. The numerical experiments on benchmark datasets show
      promising results, which confirms the effectiveness of the proposed method in
      terms of accuracy. The Matlab code and supplementary materials are available at
      http://eserver2.sat.iis.u-tokyo.ac.jp/ approximately xmzhao/proteins.html.

PMID- 18076027
TI  - Huntingtin interacting protein HYPK is intrinsically unstructured.
AB  - To characterize HYPK, originally identified as a novel huntingtin (Htt)
      interacting partner by yeast two hybrid assay, we used various biophysical and
      biochemical techniques. The molecular weight of the protein, determined by gel
      electrophoresis, was found to be about 1.3-folds ( approximately 22 kDa) higher
      than that obtained from mass spectrometric analysis (16.9 kDa). In size exclusion
      chromatography experiment, HYPK was eluted in three fractions, the hydrodynamic
      radii for which were calculated to be approximately 1.5-folds (23.06 A) higher
      than that expected for globular proteins of equivalent mass (17.3 A). The protein
      exhibited predominantly (63%) random coil characteristics in circular dichroism
      spectroscopy and was highly sensitive to limited proteolysis by trypsin and
      papain, indicating absence of any specific domain. Experimental evidences with
      theoretical analyses of amino acids composition of HYPK and comparison with
      available published data predicts that HYPK is an intrinsically unstructured
      protein (IUP) with premolten globule like conformation. In presence of increasing
      concentration of Ca(2+), HYPK showed conformational alterations as well as
      concomitant reduction of hydrodynamic radius. Even though any link between the
      natively unfolded nature of HYPK, its conformational sensitivity towards Ca(2+)
      and interaction with Htt is yet to be established, its possible involvement in
      Huntington's disease pathogenesis is discussed.

PMID- 18076028
TI  - Predicting protein homocysteinylation targets based on dihedral strain energy and
      pKa of cysteines.
AB  - A multitude of complex diseases have been linked to elevated homocysteine levels;
      however, till date there is no plausible explanation for a single amino acid's
      involvement in so many diseases. Since homocysteine is a reactive thiol amino
      acid and the majority of plasma homocysteine is protein thiol bound, we
      hypothesized that homocysteine might bind to accessible cysteine residues in
      target proteins, thereby modulating its structure or function or both. The
      parameters that dictate homocysteine-protein interaction are not well understood,
      and the few known homocysteine binding proteins were identified by a candidate
      protein approach. In this study, we identified potential homocysteine interacting
      proteins based on cysteine content, solvent accessibility of cysteine residues,
      and dihedral strain energies and pKa of these cysteines. Pathway mapping of the
      cysteine-rich proteins revealed that proteins in the coagulation cascade, notch
      receptor-mediated signaling, LDL endocytosis, programmed cell death, and
      extracellular matrix proteins were significantly over-represented with cysteine
      rich proteins, and we believe that homocysteine has a high probability to bind to
      proteins in these pathways. In fact, several clinical studies have implicated
      high homocysteine levels to be associated with diseases like thrombosis, neural
      tube defects, and so forth, which result from dysfunction of one or more of the
      proteins identified in our study. Further, we successfully validated our
      prediction parameters on the proteins that have already been experimentally shown
      to bind homocysteine, and our structural analysis argues a plausible explanation
      for these prior reported protein interactions with homocysteine that could not be
      previously explained.

PMID- 18076029
TI  - The investigation of interactions of kappa-Hefutoxin1 with the voltage-gated
      potassium channels: a computational simulation.
AB  - Kappa-Hefutoxin1 is a K(+) channel-blocking toxin from the scorpion Heterometrus
      fluvipes. It is a 22-residue protein that adapts a novel fold of two parallel
      helices linked by two disulfide bridges without beta-sheets. Recognition of
      interactions of kappa-Hefutoxin1 with the voltage-gated potassium channels,
      Kv1.1, Kv1.2, and Kv1.3, was studied by 3D-Dock software package. All structures
      of kappa-Hefutoxin1 were considered during the simulations, which indicated that
      even small changes in the structure of kappa-Hefutoxin1 considerably affected
      both the recognition and the binding between kappa-Hefutoxin1 and the Kv1
      channels. kappa-Hefutoxin1 is located around the extracellular part of the Kv1
      channels, making contacts with its helices. Lys 19, Tyr 5, Arg 6, Trp 9, or Arg
      10 in the toxin and residues Asp 402, His 404, Thr 407,Gly 401, and Asp 386 in
      each subunit of the Kv potassium channel are the key residues for the toxin
      channel recognition. Moreover, the simulation result demonstrates that the
      hydrophobic interactions are important in interaction of negatively charged
      toxins with potassium channels. The results of our docking/molecular dynamics
      simulations indicate that our 3D model structure of the kappa-Hefutoxin1-complex
      is both reasonable and acceptable and could be helpful for smarter drug design
      and the blocking agents of Kv1 channels.

PMID- 18076030
TI  - Molecular dynamics of photoreceptor synapse formation in the developing chick
      retina.
AB  - The cellular and molecular mechanisms underlying photoreceptor synaptogenesis are
      poorly understood. Furthermore, a detailed picture of the molecular composition
      of photoreceptor synapses, or their subtypes, is not yet available, nor do we
      know what differences, if any, exist among those subtypes. To address these
      questions, we investigated temporal and spatial patterns of expression and
      assembly of photoreceptor presynaptic components during chick embryo retinal
      development and early posthatched life by using reverse transcriptase polymerase
      chain reaction (RT-PCR), dissociated retinal cells, laser-capture microdissection
      (LCM), immunocytochemistry and confocal microscopy. Immunocytochemistry in tissue
      sections and dissociated cells showed many similarities and few differences in
      the synaptic composition of rods and cone subtypes, which, however, were found to
      project to different strata within the outer plexiform layer. A striking finding
      was the precise timetable of expression of synaptic genes and proteins during
      synaptogenesis. Although mRNAs for some synaptic molecules appeared as early as
      embryonic day (ED) 5-8 (the time of inner retina synaptogenesis), others were
      undetectable before the time of onset of photoreceptor synaptogenesis on ED13,
      including CAST, rim2, synapsin-2, syntaxin-3, synaptotagmin, glutamate receptors 
      1, -4, and -5, homer-1 and -2, and tenascin-R. Most synaptic proteins in
      photoreceptors followed a similar sequence of expression: they were negative or
      weakly positive before ED13, appeared in inner segments between ED13 and ED15,
      became subsequently detectable in perinuclear and axonal regions, and by ED18
      were assembled into synaptic terminals and became undetectable in the inner
      segments. The identity of the signals that regulate the coordinated expression of
      these synaptic components remains to be investigated.

PMID- 18076031
TI  - Overexpression, physicochemical characterization, and modeling of a
      hyperthermophilic pyrococcus furiosus type 2 IPP isomerase.
AB  - In the first step of this study, type 2 isopentenyl diphosphate isomerase (IDI2)
      from Pyrococcus furiosus (pf-IDI2), a hyperthermophilic microorganism, was cloned
      and overexpressed in E. coli. After purification, hyperthermophilic behavior of
      this protein was approached by means of enzymatic assays and thermal denaturation
      studies. Compared with the mesophilic Streptococcus pneumoniae IDI2, which
      unfolds and looses activity above 50 degrees C, pf-IDI2 is still folded and
      active at 80 degrees C. Molecular modeling was applied, in a parallel step, to
      understand the molecular basis of thermal stability. Comparison of IDI2 from S.
      pneumoniae, T. thermophilus, and P. furiosus suggested that additional charged
      residues present in the hyperthermophilic enzyme might contribute to its higher
      thermal stability. This could increase the number of salt bridges between
      monomers of IDI2 in P. furiosus enzyme and, hence, decrease flexibility of loops
      or N-terminal segment, thereby enhancing its thermal stability.

PMID- 18076032
TI  - Using quantum mechanics to improve estimates of amino acid side chain rotamer
      energies.
AB  - Amino acid side chains adopt a discrete set of favorable conformations typically
      referred to as rotamers. The relative energies of rotamers partially determine
      which side chain conformations are more often observed in protein structures and
      accurate estimates of these energies are important for predicting protein
      structure and designing new proteins. Protein modelers typically calculate side
      chain rotamer energies by using molecular mechanics (MM) potentials or by
      converting rotamer probabilities from the protein database (PDB) into relative
      free energies. One limitation of the knowledge-based energies is that rotamer
      preferences observed in the PDB can reflect internal side chain energies as well
      as longer-range interactions with the rest of the protein. Here, we test an
      alternative approach for calculating rotamer energies. We use three different
      quantum mechanics (QM) methods (second order Moller-Plesset (MP2), density
      functional theory (DFT) energy calculation using the B3LYP functional, and
      Hartree-Fock) to calculate the energy of amino acid rotamers in a dipeptide model
      system, and then use these pre-calculated values in side chain placement
      simulations. Energies were calculated for over 36,000 different conformations of
      leucine, isoleucine, and valine dipeptides with backbone torsion angles from the
      helical and strand regions of the Ramachandran plot. In a subset of cases these
      energies differ significantly from those calculated with standard molecular
      mechanics potentials or those derived from PDB statistics. We find that in these
      cases the energies from the QM methods result in more accurate placement of amino
      acid side chains in structure prediction tests.

PMID- 18076033
TI  - Crystal structure of the PH1932 protein, a unique archaeal ArsR type winged-HTH
      transcription factor from Pyrococcus horikoshii OT3.

PMID- 18076034
TI  - A statistical rescoring scheme for protein-ligand docking: Consideration of
      entropic effect.
AB  - Computational prediction of protein-ligand binding modes provides useful
      information on the relationship between structure and activity needed for drug
      design. A statistical rescoring method that incorporates entropic effect is
      proposed to improve the accuracy of binding mode prediction. A probability
      function for two sampled conformations to belong to the same broad basin in the
      potential energy surface is introduced to estimate the contribution of the state
      represented by a sampled conformation to the configurational integral. The
      rescoring function is reduced to the colony energy introduced by Xiang et al.
      (Proc Natl Acad Sci USA 2002;99:7432-7437) when a particular functional form for
      the probability function is used. The scheme is applied to rescore protein-ligand
      complex conformations generated by AutoDock. It is demonstrated that this simple
      rescoring improves prediction accuracy substantially when tested on 163 protein
      ligand complexes with known experimental structures. For example, the percentage
      of complexes for which predicted ligand conformations are within 1 A root-mean
      square deviation from the native conformations is doubled from about 20% to more
      than 40%. Rescoring with 11 different scoring functions including AutoDock
      scoring functions were also tested using the ensemble of conformations generated
      by Wang et al. (J Med Chem 2003;46:2287-2303). Comparison with other methods that
      use clustering and estimation of conformational entropy is provided. Examination
      of the docked poses reveals that the rescoring corrects the predictions in which
      ligands are tightly fit into the binding pockets and have low energies, but have
      too little room for conformational freedom and thus have low entropy.

PMID- 18076035
TI  - In meso crystal structure and docking simulations suggest an alternative
      proteoglycan binding site in the OpcA outer membrane adhesin.
AB  - OpcA is an integral outer membrane adhesin protein from Neisseria meningitidis,
      the causative agent of meningococcal meningitis and septicemia. It binds to
      sialic acid (SA)-containing polysaccharides on the surface of epithelial cells.
      The crystal structure of OpcA showed that the protein adopts a 10-stranded beta
      barrel structure, with five extensive loop regions on the extracellular side of
      the membrane. These form a crevice structure, lined with basic residues, which
      was hypothesized to act as the binding site for polysaccharide ligands. In the
      current study, a distinctly different OpcA structure has been obtained using
      crystals grown from a lipidic mesophase. Comparison of the two structures shows
      that the largest loop (L2), which closes over the end of the beta-barrel in the
      original crystal form, adopts a much more extended structure by reaching outward
      and away from the protein. The difference in conformation may be attributable to
      the absence of zinc ions from the crystallization conditions for the in meso
      crystal form: in the original structure, two zinc ions were bound to the external
      loops. Molecular dynamics (MD) simulations performed on the two OpcA models in a
      lipid bilayer environment demonstrated pronounced loop mobility. These
      observations support the view that the loop regions of OpcA are capable of a high
      degree of conformational flexibility. The original binding site for
      polysaccharide is not present in the in meso crystal form, and is disrupted
      during MD simulations. Docking analysis suggests a putative alternative location
      for the SA ligand in the new crystal form of OpcA.

PMID- 18076036
TI  - Structural basis of octanoic acid recognition by lipoate-protein ligase B.

PMID- 18076037
TI  - Tandem use of X-ray crystallography and mass spectrometry to obtain ab initio the
      complete and exact amino acids sequence of HPBP, a human 38-kDa apolipoprotein.
AB  - The Human Phosphate Binding Protein (HPBP) is a serendipitously discovered
      apolipoprotein from human plasma that binds phosphate. Amino acid sequence
      relates HPBP to an intriguing protein family that seems ubiquitous in eukaryotes.
      These proteins, named DING according to the sequence of their four conserved N
      terminal residues, are systematically absent from eukaryotic genome databases. As
      a consequence, HPBP amino acids sequence had to be first assigned from the
      electronic density map. Then, an original approach combining X-ray
      crystallography and mass spectrometry provides the complete and a priori exact
      sequence of the 38-kDa HPBP. This first complete sequence of a eukaryotic DING
      protein will be helpful to study HPBP and the entire DING protein family.

PMID- 18076038
TI  - Complex assembly mechanism and an RNA-binding mode of the human p14-SF3b155
      spliceosomal protein complex identified by NMR solution structure and functional
      analyses.
AB  - The spliceosomal protein p14, a component of the SF3b complex in the U2 small
      nuclear ribonucleoprotein (snRNP), is essential for the U2 snRNP to recognize the
      branch site adenosine. The elucidation of the dynamic process of the splicing
      machinery rearrangement awaited the solution structural information. We
      identified a suitable complex of human p14 and the SF3b155 fragment for the
      determination of its solution structure by NMR. In addition to the overall
      structure of the complex, which was recently reported in a crystallographic study
      (typical RNA recognition motif fold beta1-alpha1-beta2-beta3-alpha2-beta4 of p14,
      and alphaA-betaA fold of the SF3b155 fragment), we identified three important
      features revealed by the NMR solution structure. First, the C-terminal extension
      and the nuclear localization signal of p14 (alpha3 and alpha4 in the crystal
      structure, respectively) were dispensable for the complex formation. Second, the
      proline-rich segment of SF3b155, following betaA, closely approaches p14. Third,
      interestingly, the beta1-alpha1 loop and the alpha2-beta4 beta-hairpin form a
      positively charged groove. Extensive mutagenesis analyses revealed the functional
      relevance of the residues involved in the protein-protein interactions: two
      aromatic residues of SF3b155 (Phe408 and Tyr412) play crucial roles in the
      complex formation, and two hydrophobic residues (Val414 and Leu415) in SF3b 155
      serve as an anchor for the complex formation, by cooperating with the aromatic
      residues. These findings clearly led to the conclusion that SFb155 binds to p14
      with three contact points, involving Phe408, Tyr412, and Val414/Leu415.
      Furthermore, to dissect the interactions between p14 and the branch site RNA, we
      performed chemical-shift-perturbation experiments, not only for the main-chain
      but also for the side-chain resonances, for several p14-SF3b155 complex
      constructs upon binding to RNA. These analyses identified a positively charged
      groove and the C-terminal extension of p14 as RNA-binding sites. Strikingly, an
      aromatic residue in the beta1-alpha1 loop, Tyr28, and a positively charged
      residue in the alpha2-beta4 beta-hairpin, Agr85, are critical for the RNA-binding
      activity of the positively charged groove. The Tyr28Ala and Arg85Ala point
      mutants and a deletion mutant of the C-terminal extension clearly revealed that
      their RNA binding activities were independent of each other. Collectively, this
      study provides details for the protein-recognition mode of p14 and insight into
      the branch site recognition.

PMID- 18076039
TI  - Exploring the protein G helix free-energy surface by solute tempering
      metadynamics.
AB  - The free-energy landscape of the alpha-helix of protein G is studied by means of
      metadynamics coupled with a solute tempering algorithm. Metadynamics allows to
      overcome large energy barriers, whereas solute tempering improves the sampling
      with an affordable computational effort. From the sampled free-energy surface we
      are able to reproduce a number of experimental observations, such as the fact
      that the lowest minimum corresponds to a globular conformation displaying some
      degree of beta-structure, that the helical state is metastable and involves only
      65% of the chain. The calculations also show that the system populates
      consistently a pi-helix state and that the hydrophobic staple motif is present
      only in the free-energy minimum associated with the helices, and contributes to
      their stabilization. The use of metadynamics coupled with solute tempering
      results then particularly suitable to provide the thermodynamics of a short
      peptide, and its computational efficiency is promising to deal with larger
      proteins.

PMID- 18076040
TI  - Functional and structural features of the oxyanion hole in a thermophilic
      esterase from Alicyclobacillus acidocaldarius.
AB  - Recent mutagenic and molecular modelling studies suggested a role for glycine 84
      in the putative oxyanion loop of the carboxylesterase EST2 from Alicyclobacillus
      acidocaldarius. A 114 times decrease of the esterase catalytic activity of the
      G84S mutant was observed, without changes in the thermal stability. The recently
      solved three-dimensional (3D) structure of EST2 in complex with a HEPES molecule
      permitted to demonstrate that G84 (together with G83 and A156) is involved in the
      stabilization of the oxyanion through a hydrogen bond from its main chain NH
      group. The structural data in this case did not allowed us to rationalize the
      effect of the mutation, since this hydrogen bond was predicted to be unaltered in
      the mutant. Since the mutation could shed light on the role of the oxyanion loop
      in the HSL family, experiments to elucidate at the mechanistic level the reasons
      of the observed drop in k (cat) were devised. In this work, the kinetic and
      structural features of the G84S mutant were investigated in more detail. The
      optimal temperature and pH for the activity of the mutated enzyme were found
      significantly changed (T = 65 degrees C and pH = 5.75). The catalytic constants K
      (M) and V(max) were found considerably altered in the mutant, with ninefold
      increased K (M) and 14-fold decreased V(max), at pH 5.75. At pH 7.1, the decrease
      in k (cat) was much more dramatic. The measurement of kinetic constants for some
      steps of the reaction mechanism and the resolution of the mutant 3D structure
      provided evidences that the observed effects were partly due to the steric
      hindrance of the S84-OH group towards the ester substrate and partly to its
      interference with the nucleophilic attack of a water molecule on the second
      tetrahedral intermediate.

PMID- 18076041
TI  - Serum lipid levels and the risk of biliary tract cancers and biliary stones: A
      population-based study in China.
AB  - Biliary tract cancers, encompassing the gallbladder, extrahepatic bile ducts and
      ampulla of Vater, are rare but highly fatal malignancies. Gallstones, the
      predominant risk factor for biliary cancers, are linked with hyperlipidemia. As
      part of a population-based case-control study conducted in Shanghai, China, we
      examined the associations of serum lipid levels with biliary stones and cancers.
      We included 460 biliary cancer cases (264 gallbladder, 141 extrahepatic bile
      duct, and 55 ampulla of Vater), 981 biliary stone cases and 858 healthy
      individuals randomly selected from the population. Participants completed an in
      person interview and gave overnight fasting blood samples. Participants in the
      highest quintile of triglycerides (>/=160 mg/dl) had a 1.4-fold risk of biliary
      stones (95% CI = 1.1-1.9), a 1.9-fold risk of gallbladder cancer (95% CI = 1.3
      2.8), and a 4.8-fold risk of bile duct cancer (95% CI = 2.8-8.1), compared to the
      reference group (third quintile: 90-124 mg/dl). Participants in the lowest
      quintile of high-density lipoprotein (HDL) (<30 mg/dl) had a 4.2-fold risk of
      biliary stones (95% CI = 3.0-6.0), an 11.6-fold risk of gallbladder cancer (95%
      CI = 7.3-18.5), and a 16.8-fold risk of bile duct cancer (95% CI = 9.1-30.9),
      relative to the reference group (third quintile: 40-49 mg/dl). In addition, total
      cholesterol, low-density lipoprotein (LDL) and apolipoprotein A (apo A) were
      inversely associated with biliary stones; whereas low levels as well as high
      levels of total cholesterol, LDL, apo A and apolipoprotein B (apo B) were
      associated with excess risks of biliary tract cancers. Our findings support a
      role for serum lipids in gallstone development and biliary carcinogenesis.

PMID- 18076042
TI  - Hepatitis B and C virus infection and the risk of biliary tract cancer: a
      population-based study in China.
AB  - Emerging data suggest that chronic hepatitis B virus (HBV) and hepatitis C virus
      (HCV) infections may also play a role in extrahepatic bile duct cancers. To test
      the HBV hypothesis, we examined the relationship of HBV/HCV infection with risks
      of biliary tract cancer and biliary stones in a population-based case-control
      study conducted in Shanghai, China. Standard assays were used to detect HBV
      surface antigen (HBsAg) and antibodies against HBV core antigen (anti-HBc) and
      hepatitis C virus (anti-HCV) in sera from 417 patients with biliary tract
      cancers, 517 with biliary stones, and 762 healthy controls randomly selected from
      the population. Unconditional logistic regression was used to calculate the odds
      ratios (ORs) and 95% confidence intervals (CIs) for each disease type. HBsAg
      seroprevalence was 7.3% among population controls and 14.2% among patients with
      extrahepatic bile duct cancer, resulting in a 2.4-fold risk of extrahepatic bile
      duct cancer (95% CI 1.2-4.5). No association was found for cancers of the
      gallbladder (prevalence 8.2%) or the ampulla of Vater (6.1%), or for stones in
      the gallbladder (10.1%) or bile duct (9.3%). Further adjustment for education,
      smoking, body mass index, diabetes and gallstones did not materially change the
      results. Prevalence of HCV infection in this population was low (2%), limiting
      our ability to detect an association with biliary diseases. In Shanghai, an HBV
      endemic area, chronic HBV infection was associated with a 2.4-fold risk of
      extrahepatic bile duct cancer. These results should be confirmed in other
      populations with varying risks of HBV and HCV infection.

PMID- 18076043
TI  - Family history and the risk of oral and pharyngeal cancer.
AB  - Scanty data are available on familial risk in oral and pharyngeal cancer. The
      relationship between oral and pharyngeal cancer and family history of cancer in
      first-degree relatives was investigated using data from a multicentric case
      control study conducted in Italy and Switzerland between 1992 and 2005 on 956
      cases aged less than 79 years, with histologically confirmed incident oral and
      pharyngeal cancer, and 2362 controls admitted to hospital for acute,
      nonneoplastic conditions. Logistic regression models conditioned on sex, age,
      study centre, and including terms for education, tobacco smoking, alcohol
      drinking, and number of siblings were used to estimate the odds ratios (OR) of
      oral and pharyngeal cancer. The multivariate ORs were similar for a family
      history of oral and pharyngeal cancer (2.6, 95% confidence interval, CI, 1.5-4.5)
      and laryngeal cancer (3.8, 95% CI, 2.0-7.2). The OR was 3.1 (95% CI, 2.0-4.8) for
      oral and pharyngeal cancer and laryngeal cancer combined. The OR was 7.1 (95% CI,
      1.3-37.2) for subjects with 2 or more first-degree relatives with oral and
      pharyngeal/laryngeal cancers. Significant increases in risk were also observed
      for a family history of melanoma (OR = 5.8; 95% CI, 1.3-26.4) and lung cancer (OR
      = 1.4; 95% CI, 1.0-2.0). Compared to subjects without family history, nonsmokers,
      and non or moderate drinkers, the OR was 42.6 for current smokers, heavy drinkers
      with family history. History of oral and pharyngeal cancer and laryngeal cancer
      is a strong determinant of oral and pharyngeal cancer risk, independent from
      tobacco and alcohol.

PMID- 18076044
TI  - Colorectal cancer cells express functional cell surface-bound TGFbeta.
AB  - Disruptions to the TGFbeta signaling pathway have been implicated in most human
      adenocarcinomas. In addition to its role in cancer cell migration and metastasis,
      TGFbeta has been implicated in tumor-mediated immunosuppression. Membrane-bound
      TGFbeta has previously been reported to be expressed on a subset of regulatory T
      cells and was shown to be critical to their immune suppressive function. In the
      present study, we document expression of a signaling competent, endogenously
      derived form of cell surface-bound TGFbeta on colorectal cancer cells. While
      antibodies against only the mature form of TGFbeta failed to label cells, surface
      bound TGFbeta was clearly detected by antibodies specific for both the latent and
      mature forms of the cytokine. Confirming the notion that the surface TGFbeta was
      in latent form, brief acid pulsing of the cells increased the amount of
      detectable membrane-associated TGFbeta. In coculture assays, this cell-bound
      TGFbeta could be activated and utilized in a paracrine fashion both by other
      cancer cells and by CD8+ intraepithelial lymphocytes. This effect was abrogated
      by the use of a furin inhibitor which decreased the membranous expression of
      TGFbeta on the tumor cells. Signaling competent membrane-bound TGFbeta on cancer
      cells is thus likely to be a key player in regulating tumor cell interactions
      with each other as well as with other cells in their microenvironment.

PMID- 18076045
TI  - Long term cannabinoid receptor (CB1) blockade in obesity: implications for the
      development of colorectal cancer.

PMID- 18076046
TI  - Predicting protein interaction interfaces from protein sequences: case studies of
      subtilisin and phycocyanin.
AB  - Identification of protein interaction interfaces is very important for
      understanding the molecular mechanisms underlying biological phenomena. Here, we
      present a novel method for predicting protein interaction interfaces from
      sequences by using PAM matrix (PIFPAM). Sequence alignments for interacting
      proteins were constructed and parsed into segments using sliding windows. By
      calculating distance matrix for each segment, the correlation coefficients
      between segments were estimated. The interaction interfaces were predicted by
      extracting highly correlated segment pairs from the correlation map. The
      predictions achieved an accuracy 0.41-0.71 for eight intraprotein interaction
      examples, and 0.07-0.60 for four interprotein interaction examples. Compared with
      three previously published methods, PIFPAM predicted more contacting site pairs
      for 11 out of the 12 example proteins, and predicted at least 34% more contacting
      site pairs for eight proteins of them. The factors affecting the predictions were
      also analyzed. Since PIFPAM uses only the alignments of the two interacting
      proteins as input, it is especially useful when no three-dimensional protein
      structure data are available.

PMID- 18076047
TI  - Cysteine 10 is critical for the activity of Ochrobactrum anthropi glutathione
      transferase and its mutation to alanine causes the preferential binding of
      glutathione to the H-site.
AB  - The role of the evolutionarily conserved residue Cys10 in Ochrobactrum anthropi
      glutathione transferase (OaGST) has been examined by replacing it with an
      alanine. A double mutant C10A/S11A was also prepared. The effect of the
      replacements on the coniugating and thiotransferase activities, and on the
      thermal and chemical stability of the enzyme was analyzed. Our data support the
      view that in OaGST, in contrast with other beta class GSTs that display
      significant differences in the glutathione-binding site, Cys10 is a key residue
      for glutathione coniugating activity. Furthermore, analysis of the OaGST-Cys10Ala
      structure, crystallized in the presence of glutathione, reveals that this
      mutation causes a switch between the high-affinity G-site and a low-affinity H
      site where hydrophobic cosubstrates bind and where we observe the presence of an
      unexpected glutathione.

PMID- 18076048
TI  - Remote homology detection of integral membrane proteins using conserved sequence
      features.
AB  - Compared with globular proteins, transmembrane proteins are surrounded by a more
      intricate environment and, consequently, amino acid composition varies between
      the different compartments. Existing algorithms for homology detection are
      generally developed with globular proteins in mind and may not be optimal to
      detect distant homology between transmembrane proteins. Here, we introduce a new
      profile-profile based alignment method for remote homology detection of
      transmembrane proteins in a hidden Markov model framework that takes advantage of
      the sequence constraints placed by the hydrophobic interior of the membrane. We
      expect that, for distant membrane protein homologs, even if the sequences have
      diverged too far to be recognized, the hydrophobicity pattern and the
      transmembrane topology are better conserved. By using this information in
      parallel with sequence information, we show that both sensitivity and specificity
      can be substantially improved for remote homology detection in two independent
      test sets. In addition, we show that alignment quality can be improved for the
      most distant homologs in a public dataset of membrane protein structures.
      Applying the method to the Pfam domain database, we are able to suggest new
      putative evolutionary relationships for a few relatively uncharacterized protein
      domain families, of which several are confirmed by other methods. The method is
      called Searcher for Homology Relationships of Integral Membrane Proteins (SHRIMP)
      and is available for download at http://www.sbc.su.se/shrimp/.

PMID- 18076049
TI  - The C-terminal region of thermophilic tRNA (m7G46) methyltransferase (TrmB)
      stabilizes the dimer structure and enhances fidelity of methylation.
AB  - Transfer RNA (m(7)G46) methyltransferase catalyzes methyl-transfer from S
      adenosyl-L-methionine to N(7) atom of the semi-conserved G46 base in tRNA.
      Aquifex aeolicus is a hyper thermophilic eubacterium that grows at close to 95
      degrees C. A. aeolicus tRNA (m(7)G46) methyltransferase [TrmB] has an elongated C
      terminal region as compared with mesophilic counterparts. In this study, the
      authors focused on the functions of this C-terminal region. Analytic gel
      filtration chromatography and amino acid sequencing reveled that the start point
      (Glu202) of the C-terminal region is often cleaved by proteases during
      purification steps and the C-terminal region tightly binds to another subunit
      even in the presence of 6M urea. Because the C-terminal region contains abundant
      basic amino acid residues, the authors assumed that some of these residues might
      be involved in tRNA binding. To address this idea, the authors prepared eight
      alanine substitution mutant proteins. However, measurements of initial velocities
      of these mutant proteins suggested that the basic amino acid residues in the C
      terminal region are not involved in tRNA binding. The authors investigated
      effects of the deletion of the C-terminal region. Deletion mutant protein of the
      C-terminal region (the core protein) was precipitated by incubation at 85 degrees
      C, while the wild type protein was soluble at that temperature, demonstrating
      that the C-terminal region contributes to the protein stability at high
      temperatures. The core protein had a methyl-transfer activity to yeast tRNA(Phe)
      transcript. Furthermore, the core protein slowly methylated tRNA transcripts,
      which did not contain G46 base. Moreover, the modified base was identified as
      m(7)G by two-dimensional thin layer chromatography. Thus, the deletion of the C
      terminal region causes nonspecific methylation of N(7) atom of guanine base(s) in
      tRNA transcripts.

PMID- 18076050
TI  - Distant homology detection using a LEngth and STructure-based sequence Alignment
      Tool (LESTAT).
AB  - A new machine learning algorithm, LESTAT (LEngth and STructure-based sequence
      Alignment Tool) has been developed for detecting protein homologs having low
      sequence identity. LESTAT is an iterative profile-based method that runs without
      reliance on a predefined library and incorporates several novel features that
      enhance its ability to identify remote sequences. To overcome the inherent bias
      associated with a single starting model, LESTAT utilizes three structural
      homologs to create a profile consisting of structurally conserved positions and
      block separation distances. Subsequent profiles are refined iteratively using
      sequence information obtained from previous cycles. Additionally, the refinement
      process incorporates a "lock-in" feature to retain the high-scoring sequences
      involved in previous alignments for subsequent model building and an enhancement
      factor to complement the weighting scheme used to build the position specific
      scoring matrix. A comparison of the performance of LESTAT against PSI-BLAST for
      seven systems reveals that LESTAT exhibits increased sensitivity and specificity
      over PSI-BLAST in six of these systems, based on the number of true homologs
      detected and the number of families these homologs covered. Notably, many of the
      hits identified are unique to each method, presumably resulting from the distinct
      differences in the two approaches. Taken together, these findings suggest that
      LESTAT is a useful complementary method to PSI-BLAST in the detection of distant
      homologs.

PMID- 18076051
TI  - The point mutation A34F causes dimerization of GB1.
AB  - The immunoglobulin-binding domain B1 of streptococcal protein G (GB1), a very
      stable, small, single-domain protein, is one of the most extensively used models
      in the area of protein folding and design. Variants derived from a library of
      randomized hydrophobic core residues previously revealed alternative folds,
      namely a completely intertwined tetramer (Frank et al., Nat Struct Biol
      2002;9:877-885) and a domain-swapped dimer (Byeon et al., J Mol Biol 2003;333:141
      152). Here, we report the NMR structure of the single amino acid mutant Ala-34
      Phe which exists as side-by-side dimer. The dimer dissociation constant is 27 +/-
      4 microM. The dimer interface comprises two structural elements: First, the beta
      sheets of the two monomers pair in an antiparallel arrangement, thereby forming
      an eight-stranded beta-sheet. Second, the alpha-helix is shortened, ending in a
      loop that engages in intermolecular contacts. The largest difference between the
      monomer unit in the A34F dimer and the monomeric wild-type GB1 is the dissolution
      of the C-terminal half of the alpha-helix associated with a pronounced slow
      conformational motion of the interface loop. This involves a large movement of
      the Tyr-33 side chain that swings out from the monomer to engage in dimer
      contacts.

PMID- 18076052
TI  - Pressure-induced changes in the solution structure of the GB1 domain of protein
      G.
AB  - The solution structure of the GB1 domain of protein G at a pressure of 2 kbar is
      presented. The structure was calculated as a change from an energy-minimised low
      pressure structure using (1)H chemical shifts. Two separate changes can be
      characterised: a compression/distortion, which is linear with pressure; and a
      stabilisation of an alternative folded state. On application of pressure, linear
      chemical shift changes reveal that the backbone structure changes by about 0.2 A
      root mean square, and is compressed by about 1% overall. The alpha-helix
      compresses, particularly at the C-terminal end, and moves toward the beta-sheet,
      while the beta-sheet is twisted, with the corners closest to the alpha-helix
      curling up towards it. The largest changes in structure are along the second beta
      strand, which becomes more twisted. This strand is where the protein binds to
      IgG. Curved chemical shift changes with pressure indicate that high pressure also
      populates an alternative structure with a distortion towards the C-terminal end
      of the helix, which is likely to be caused by insertion of a water molecule.

PMID- 18076053
TI  - Probing electrostatic interactions and ligand binding in aspartyl-tRNA synthetase
      through site-directed mutagenesis and computer simulations.
AB  - Faithful genetic code translation requires that each aminoacyl-tRNA synthetase
      recognise its cognate amino acid ligand specifically. Aspartyl-tRNA synthetase
      (AspRS) distinguishes between its negatively-charged Asp substrate and two
      competitors, neutral Asn and di-negative succinate, using a complex network of
      electrostatic interactions. Here, we used molecular dynamics simulations and site
      directed mutagenesis experiments to probe these interactions further. We attempt
      to decrease the Asp/Asn binding free energy difference via single, double and
      triple mutations that reduce the net positive charge in the active site of
      Escherichia coli AspRS. Earlier, Glutamine 199 was changed to a negatively
      charged glutamate, giving a computed reduction in Asp affinity in good agreement
      with experiment. Here, Lysine 198 was changed to a neutral leucine; then, Lys198
      and Gln199 were mutated simultaneously. Both mutants are predicted to have
      reduced Asp binding and improved Asn binding, but the changes are insufficient to
      overcome the initial, high specificity of the native enzyme, which retains a
      preference for Asp. Probing the aminoacyl-adenylation reaction through
      pyrophosphate exchange experiments, we found no detectable activity for the
      mutant enzymes, indicating weaker Asp binding and/or poorer transition state
      stabilization. The simulations show that the mutations' effect is partly offset
      by proton uptake by a nearby histidine. Therefore, we performed additional
      simulations where the nearby Histidines 448 and 449 were mutated to neutral or
      negative residues: (Lys198Leu, His448Gln, His449Gln), and (Lys198Leu, His448Glu,
      His449Gln). This led to unexpected conformational changes and loss of active site
      preorganization, suggesting that the AspRS active site has a limited structural
      tolerance for electrostatic modifications. The data give insights into the
      complex electrostatic network in the AspRS active site and illustrate the
      difficulty in engineering charged-to-neutral changes of the preferred ligand.

PMID- 18076054
TI  - Xenobiotic activity in serum and sperm chromatin integrity in European and inuit
      populations.
AB  - Lipophilic persistent organic pollutants (POPs) are ubiquitous in the environment
      and suspected to interfere with hormone activities and reproduction. In previous
      studies we demonstrated that POP exposure can affect sperm DNA integrity and
      differences between Inuits and Europeans in sperm DNA integrity and xenobiotic
      activity were observed. The aim of this study was to investigate possible
      relations between human sperm chromatin integrity and the xenobiotic serum
      activity of lipophilic POPs assessed as effects on the estrogen (ER), androgen
      (AR), and/or aryl hydrocarbon (AhR) receptors. Human sperm chromatin integrity
      was assessed as DNA fragmentation index (%DFI) and high DNA stainability (%HDS)
      using the flow cytometric sperm chromatin structure assay (SCSA). Xenobiotic
      receptor activities were determined using chemically activated luciferase gene
      expression (CALUX) assay. The study included 53 Greenlandic Inuits and 247
      Europeans (Sweden, Warsaw (Poland) and Kharkiv (Ukraine)). A heterogeneous
      pattern of correlations was found. For Inuits, ER and AhR activities and %DFI
      were inversely correlated, whereas a positive correlation between AR activity and
      %DFI was found for Europeans. In contrast, no correlation between receptor
      activities and %HDS was observed for Inuits but for Europeans positive and
      negative correlations were observed between ER and AR activities and %HDS,
      respectively. We suggest that the different patterns of xenobiotic serum
      activities, in combination with diet associated factors and/or genetics, might be
      connected to the observed differences in sperm chromatin integrity between the
      Inuits and Europeans.

PMID- 18076055
TI  - Tensile tests of polymers at low temperatures in the environmental scanning
      electron microscope: an improved cooling platform.
AB  - The investigation of the fracture behavior of polymers in the environmental
      scanning electron microscope (ESEM) can provide information about the correlation
      between the microstructure of a specimen and the macroscopic stress-strain
      characteristic. As the mechanical properties of polymers change dramatically at
      the glass transition temperature, cooling of the specimens during the tensile
      tests can yield very valuable information about the influence of individual
      components of polymer blends on the fracture behavior of the material. A serious
      problem in this connection is the poor heat conductivity of polymers. A
      commercially available cooling platform, which can be mounted on the tensile
      stage used for the tests was substantially modified to both enhance the heat
      transfer between platform and specimen, and to minimize the temperature gradient
      along the specimen. The first experiments on modified polypropylene specimens
      already delivered some unexpected results. Fibril-like structures appeared at the
      crack tip that would not be expected at temperatures below the glass transition
      temperature of the polymer blend.

PMID- 18076056
TI  - Characterization of lead zirconate titanate--lanthanum ruthenate thin film
      structures prepared by chemical solution deposition.
AB  - In this work, the results of compositional and microstructural analysis of lead
      zirconate titanate--lanthanum ruthenate thin film structures prepared by chemical
      solution deposition are discussed. The cross-section transmission electron
      microscope (TEM) micrographs of the La-Ru-O film deposited on a SiO2/Si substrate
      and annealed at 700 degrees C revealed RuO2 crystals embedded in a glassy
      silicate matrix. When the La-Ru-O film was deposited on a Pt/TiO2/SiO2/Si
      substrate, RuO2 and La4Ru6O19 crystallized after annealing at 700 degrees C.
      After firing at 550 degrees C randomly oriented lead zirconate titanate (PZT)
      thin films crystallized on the La-Ru-O/SiO2/Si substrate, while on La-Ru
      O/Pt/TiO2/SiO2/Si substrates PZT thin films with (111) preferred orientation were
      obtained. No diffusion of the Ru atoms in the PZT film was found. Ferroelectric
      response of PZT thin films on these substrates is shown in comparison with the
      PZT film deposited directly on the Pt/TiO2/SiO2/Si substrate without a La-Ru-O
      layer.

PMID- 18076057
TI  - Identification, developmental expression, and functions of bursicon in the
      tobacco hawkmoth, Manduca sexta.
AB  - During posteclosion, insects undergo sequential processes of wing expansion and
      cuticle tanning. Bursicon, a highly conserved neurohormone implicated in
      regulation of these processes, was characterized recently as a heterodimeric
      cystine knot protein in Drosophila melanogaster. Here we report the predicted
      precursor sequences of bursicon subunits (Masburs and Maspburs) in the moth
      Manduca sexta. Distinct developmental patterns of mRNA transcript and subunit
      specific protein labeling of burs and pburs as well as crustacean cardioactive
      peptide in neurons of the ventral nervous system were observed in pharate larval,
      pupal, and adult stages. A subset of bursicon neurons located in thoracic ganglia
      of larvae expresses ecdysis-triggering hormone (ETH) receptors, suggesting that
      they are direct targets of ETH. Projections of bursicon neurons within the CNS
      and to neurohemal secretory sites are consistent with both central signaling and
      circulatory hormone functions. Intrinsic cells of the corpora cardiaca contain
      pburs transcripts and pburs-like immunoreactivity, whereas burs transcripts and
      burs-like immunoreactivity were absent in these cells. Recombinant bursicon
      induces both wing expansion and tanning, whereas synthetic eclosion hormone
      induces only wing expansion.

PMID- 18076058
TI  - Developmental changes of serotonin 4(a) receptor expression in the rat pre
      Botzinger complex.
AB  - Serotonin receptors (5-HTRs) are known to be involved in the regulation of
      breathing behavior and to mediate neurotrophic actions that exert a significant
      function in network formation during development. We studied neuronal 5-HT(4(a))R
      immunoreactivity (-IR) at developmental ages from E14 to P10. Within the pre
      Botzinger complex (pre-BotC), a part of the respiratory network important for
      rhythmogenesis, 5-HT(4(a))R-IR was most extensive in rats at an age of E18. The 5
      HT(4(a))-IR was found predominantly in the neuropil, whereas somatic staining was
      sporadic at late embryonic (E18-E20) stages. At birth, we observed a dramatic
      change to a predominantly somatic staining, and neuropil staining was greatly
      reduced and disappeared at an age of P4. In all developmental stages, 5-HT(4(a))
      and mu-opioid receptors were strongly coexpressed in neurons of the pre-BotC,
      whereas 5-HT(4(a))R expression was absent in neurons within the dorsal horn.
      Nestin, a marker for CNS progenitor cells, was used to obtain information about
      the degree of pre-BotC differentiation. Nestin-positive cells did not appear
      within the pre-BotC before age E20. At E16, nestin-expressing cells were absent
      in the nucleus ambiguus (NA) and its ventral periphery. The number of nestin
      positive cells increased after birth within and outside the pre-BotC, the
      majority of cells being glial. Coexpression of nestin and 5-HT(4(a))R was
      localized predominantly within the NA and appeared only sporadically within the
      pre-BotC. We conclude that 5-HT(4(a))Rs are important not only for
      neuromodulation of cellular excitability but also for respiratory network
      formation.

PMID- 18076059
TI  - The fovea regulates symmetrical development of the visual cortex.
AB  - The foveal region contains the highest cell density in the human retina;
      consequently a disproportionately large area of the visual cortex is dedicated to
      its representation. In aniridia and albinism the fovea does not develop, and the
      corresponding cortical representation shows a reduction in gray matter volume. In
      albinos there are chiasmatic irregularities in the hemispheric projections, which
      are not found in aniridics. Here, we ask whether the anomalies in central retinal
      development, present in albinism and aniridia, have a wider impact on the
      architecture of the visual cortex. The length, depth, and topology of the
      calcarine fissure is analyzed in albino, aniridic, and normal subjects. These
      measures are compared between groups and between the cortical hemispheres within
      each subject. We show that the calcarine fissure, where the primary visual cortex
      is represented, is abnormally short in those lacking a fovea. Moreover, surface
      reconstructions of the calcarine fissure revealed marked interhemispheric
      asymmetries. The two groups could not be distinguished on the basis of their
      cortical features, and we therefore interpret the abnormalities in cortical
      architecture in terms of the absence of the fovea, the common retinal feature
      found in both groups.

PMID- 18076060
TI  - Decoupled syndecan 1 mRNA and protein expression is differentially regulated by
      angiotensin II in macrophages.
AB  - It has been established that syndecan-1 is an important modulator of events
      relevant to acute tissue repair and chronic injury responses. The current studies
      were designed to examine syndecan-1 expression during atherosclerotic lesion
      formation and whether angiotensin II influences syndecan-1 expression in
      macrophages. ApoE knockout mice maintained on an atherogenic diet were treated
      for 8 weeks with an infusion of angiotensin II to induce atherosclerosis.
      Immunohistochemistry was employed to characterize the expression of syndecan-1 in
      atherosclerotic lesions. Quantitative real-time PCR (QRTPCR) was used to define
      the role of angiotensin II and responsible signaling pathways involved syndecan-1
      expression in RAW264.7 murine macrophages. Protein expression and shedding were
      characterized by fluorescence activated cell sorting (FACS) and slot blot
      analysis. Syndecan-1 was abundantly expressed in macrophages located within early
      atherosclerotic lesions. Accordingly, we hypothesized that angiotensin II
      regulates syndecan-1 expression in macrophages. A time- and dose-dependent study
      was performed in RAW264.7 macrophages. QRTPCR demonstrated maximum syndecan-1
      mRNA up-regulation at 6 h after 500 nM AgII stimulation (threefold; P < 0.05).
      Through administration of specific inhibitors, we established that ERK/MAPK, PI3K
      and JNK signaling pathways mediated this effect. FACS and slot blot analyses
      demonstrated that cAMP induced posttranscriptional syndecan-1 protein expression
      in a dose-dependent manner with or without initial angiotensin II stimulation. In
      particular, angiotensin II induced an increase in cell surface syndecan-1 (mean
      fluorescence intensity: 147 +/- 5.7 vs. 176 +/- 4.8; P < 0.05; n = 3) and
      accelerated syndecan-1 shedding. Angiotensin II is a potent regulator of syndecan
      1 expression in atherosclerotic lesions via a specific effect on macrophages that
      is mediated by ERK/MAPK, PI3K, and JNK signaling pathways.

PMID- 18076061
TI  - The effects of observer presence on the behavior of Cebus capucinus in Costa
      Rica.
AB  - We report on the responses of Cebus capucinus in the Santa Rosa Sector of the
      Area de Conservacion Guanacaste, Costa Rica, to the presence of observers over a
      4-week period. Study groups were habituated to different degrees: (1) Cerco de
      Piedra (CP): continuous observations began in 1984; (2) Exclosure (EX): focus of
      an 18-month study on males from 1998 to 1999; and (3) NBH: never studied/followed
      but the group frequently encounters researchers. We collected three types of
      data: group scans (group state was coded as calm or agitated at observer
      presence), focal animal data (observer-directed behaviors were recorded), and
      fecal cortisol levels. The two less-habituated groups (NBH and EX) differed
      significantly from the habituated group (CP) in their behavioral and cortisol
      responses, and they showed an increase in habituation over the study period
      (agitation and cortisol levels both dropped). Individuals in NBH also decreased
      their responses to observers during focal follows; however, at the end of the
      study the responses of the two less-habituated groups (NBH and EX) remained
      elevated in comparison to the habituated group (CP), suggesting the need for
      further habituation. Unlike capuchin groups that rarely encounter humans, NBH and
      EX never fled from observers and they rarely emitted observer-directed alarm
      calls. We suggest that the permanence of habituation and the ability to habituate
      animals passively through a neutral human presence are both important
      considerations for researchers conducting studies in areas where animal safety
      from poachers, etc. cannot be guaranteed.

PMID- 18076062
TI  - Cyclooxygenase inhibitors induce apoptosis in sinonasal cancer cells by increased
      expression of nonsteroidal anti-inflammatory drug-activated gene.
AB  - Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) has recently been
      shown to be induced by nonsteroidal anti-inflammatory drugs (NSAIDs) and to have
      proapoptotic and antitumorigenic activities. Although sulindac sulfide induced
      apoptosis in sinonasal cancer cells, the relationship between NAG-1 and NSAIDs
      has not been determined. In this study, we investigated the induction of
      apoptosis in sinonasal cancer cells treated by various NSAIDs and the role of NAG
      1 expression in this induction. The effect of NSAIDs on normal human nasal
      epithelial (NHNE) cells was also examined to evaluate their safety on normal
      cells. Finally, the in vivo anti-tumorigenic activity of NSAIDs in mice was
      investigated. In AMC-HN5 human sinonasal carcinoma cells, indomethacin was the
      most potent NAG-1 inducer and caused NAG-1 expression in a time- and dose
      dependent manner. The induction of NAG-1 expression preceded the induction of
      apoptosis. Conditioned medium from NAG-1-overexpressing Drosophila cells
      inhibited proliferation of sinonasal cancer cells and induced apoptosis. In
      addition, in NAG-1 small interfering RNA-transfected cells, apoptosis induced by
      indomethacin was suppressed. In contrast, NAG-1 expression and apoptosis were not
      induced by NSAIDs or conditioned medium in NHNE cells. Furthermore, indomethacin
      induced a dose-dependent in vivo increase in the expression of NAG-1 mRNA in the
      mice tumors and the volume of xenograft tumors of AMC-HN5 cells in indomethacin
      treated nude mice was reduced compared to that in control mice. In conclusion,
      indomethacin exerts proapoptotic and antitumorigenic effects in sinonasal cancer
      cells through the induction of NAG-1 and can be considered a safe and effective
      chemopreventive agent against sinonasal cancer.

PMID- 18076063
TI  - Nox1 downstream of 12-lipoxygenase controls cell proliferation but not cell
      spreading of colon cancer cells.
AB  - The catalytic subunit of the NADPH oxidase complex, Nox1 (homologue of
      gp91phox/Nox2), expressed mainly in intestinal epithelial and vascular smooth
      muscle cells, functions in innate immune defense and cell proliferation. The
      molecular mechanisms underlying these functions, however, are not completely
      understood. We measured Nox1-dependent O2- production during cell spreading on
      Collagen IV (Coll IV) in colon carcinoma cell lines. Knocking down Nox1 by shRNA,
      we showed that Nox1-dependent O2- production is activated during cell spreading
      after 4 hr of adhesion on Collagen IV. Nox1 activation during cell spreading
      relies on Rac1 activation and arachidonic metabolism. Our results showed that
      manoalide (a secreted phospholipase A2 inhibitor) and cinnamyl-3,4-dihydroxy
      alpha-cyanocinnamate (a 12-lipoxygenase inhibitor) inhibit O2- production, cell
      spreading and cell proliferation in these colonic epithelial cells. 12
      Lipoxygenase inhibition of ROS production and cell spreading can be reversed by
      adding 12-HETE, a 12-lipoxygenase product, supporting the specific effect
      observed with cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate. In contrast, Nox1
      shRNA and DPI (NADPH oxidase inhibitor) weakly affect cell spreading while
      inhibiting O2- production and cell proliferation. These results suggest that the
      12-lipoxygenase pathway is upstream of Nox1 activation and controls cell
      spreading and proliferation, while Nox1 specifically affects cell proliferation.

PMID- 18076064
TI  - Vaccine-related HPV genotypes in women with and without cervical cancer in
      Mozambique: burden and potential for prevention.
AB  - Knowledge about the burden of Human Papillomavirus (HPV) infections in Sub
      Saharan Africa is very limited. We collected cervical samples from 262 women from
      the general population and 241 tumor samples from women with invasive cervical
      cancer in Mozambique and tested them for HPV genotyping by the SPF(10)-LiPA(25)
      PCR system. Among the 195 women without cervical abnormalities by cytology HPV
      prevalence was 75.9%. In this group of women, the most frequently identified HPV
      types among HPV-positive women were in descending order of frequency: HPV51
      (23.6%), HPV35 (19.6%), HPV18 (14.2%), HPV31 (13.5%) and HPV52 (12.8%). In women
      with cervical cancer HPV DNA detection was 100%. The type-specific distribution
      of the most frequent types in descending order of frequency was: HPV16 (47.0%),
      HPV18 (31.3%), HPV51 (14.8%), HPV52 (14.3%), HPV45 (12.6%), HPV35 (10.4%), HPV33
      (4.8%) and HPV31 (2.6%). HPVs 16/18 and HPVs 16/18/31/45 were detected in 71.7%
      and 80.9% of cervical cancer tissue, respectively. While HPVs 51 and 35 were the
      two most common types in cytologically normal women in Mozambique, HPVs 16 and 18
      remained the two most frequently identified types in cervical cancer. The
      introduction of an efficacious HPV 16/18 vaccine could potentially prevent the
      occurrence of 72% of cervical cancer cases and up to 81% of the cases if full
      cross-protection against HPVs 31 and 45 is assumed.

PMID- 18076065
TI  - Mismatch repair expression in testicular cancer predicts recurrence and survival.
AB  - We investigated mismatch repair (MMR) gene expression in testicular cancer as a
      molecular marker for clinical outcome (recurrence, response to chemotherapy and
      death) using protein expression and specific genetic alterations associated with
      the presence or absence of MMR activity. One hundred sixty-two cases of paraffin
      embedded testis cancer specimens were subjected to immunohistochemical analysis
      using monoclonal antibody for MLH1 and MSH2 MMR proteins and genetic analysis
      using specific polymorphic markers. The degree of MMR immunoreactivity and
      genetic instability in the form of loss of heterozygosity (LOH) and/or
      microsatellite instability (MSI) were determined by comparing matched normal and
      tumor tissue. The degree of immunohistochemical staining for MMR expression was
      associated with a shorter time to tumor recurrence, resistance to chemotherapy
      and death. Furthermore, clinical relapse and cancer specific death was also
      associated with tumors exhibiting a high degree of MSI, p = 0.01 and 0.04,
      respectively. In contrast, LOH was not associated with recurrence, resistance to
      chemotherapy or death. Therefore, MMR expression defines testis cancers with
      distinct molecular properties and clinical behavior, such that tumors with
      decreased MMR immunostaining and/or increased frequency of MSI have a shorter
      time to recurrence and death despite chemotherapy.

PMID- 18076066
TI  - Elimination of regulatory T cells is essential for an effective vaccination with
      tumor lysate-pulsed dendritic cells in a murine glioma model.
AB  - Both melanoma and glioma cells are of neuroectodermal origin and share common
      tumor associated antigens. In this article, we report that the melanocyte
      differentiation antigen TRP2 (tyrosinase-related protein 2) is not predominantly
      involved in the tumor rejection of a syngeneic murine glioma. Although GL261
      glioma cells endogenously expressed TRP2 and were lysed by TRP2 specific
      cytotoxic T cells (CTLs) in vitro, vaccinations with TRP2 peptide-pulsed
      dendritic cells (DCs) could only induce minor antiglioma responses in a
      prophylactic setting and failed to work in a stringent setting where vaccine and
      tumor were administered on the same day. Further analysis revealed that TRP2 is
      not recognized by bulk CTLs after depletion of regulatory T cells which results
      in tumor rejections in vivo. In contrast to TRP2 peptide-pulsed DC, tumor lysate
      pulsed DCs were more potent as a vaccine and completely protected mice from tumor
      outgrowth in a prophylactic setting. However, the vaccine efficacy of tumor
      lysate-pulsed DC was not sufficient to prevent the tumor outgrowth when tumors
      were inoculated the same day. In this case, Treg depletion before vaccination was
      essential to boost antiglioma immune responses leading to the rejection of 80% of
      the mice and long-term immunity. Therefore, we conclude that counteracting the
      immunosuppressive glioma tumor environment via depletion of regulatory T cells is
      a prerequisite for successful eradication of gliomas after targeting multiple
      tumor antigens by using tumor lysate-pulsed DCs as a vaccine in a more stringent
      setting.

PMID- 18076067
TI  - Temporal trends in the incidence rate of childhood cancer in Germany 1987-2004.
AB  - The German Childhood Cancer Registry regularly presents graphs of childhood
      cancer incidence rates by period, but no systematic analysis. The Automated
      Childhood Cancer Information System-project found an increasing trend in Europe.
      Against this background we present the first detailed trend analysis of childhood
      (aged under 15) malignancies in Germany. We examined incidence rates separately
      in western Germany 1987-2004 and eastern Germany 1991-2004. We analyzed all
      malignancies, all main diagnostic groups and relevant subsets using an age-period
      cohort model. Additionally we fitted fractional polynomials to assess the
      linearity of the drift. All malignancies combined (excluding Central Nervous
      System-tumors and neuroblastoma) show a significant trend: +0.7% in western and
      +1.1% per year in eastern Germany. The overall trend in Germany is mostly due to
      the significant increase in lymphoid leukemia, which increased significantly in
      western Germany (+0.7% per year) and significantly nonlinearly in eastern Germany
      (+3.3% per year until 1998, +0.8% since 1998), catching up from a level 20% below
      western Germany. This could be due to life style changes since the reunification
      in eastern Germany influencing early immune system training. We found no trends
      for acute non-lymphocytic leukemia and non-Hodgkin lymphoma. Hodgkin's disease
      shows a cohort effect in western Germany after reunification. Improved
      registration of CNS tumors led to an increase. Neuroblastoma yielded a period
      effect in western Germany due to screening. With the exception of germ cell
      tumors, further observations for solid tumor entities are in agreement with those
      reported for Europe.

PMID- 18076068
TI  - Hypothyroidism among pediatric cancer patients: a nationwide, registry-based
      study.
AB  - The aim of the study was to determine the incidence and prevalence of
      hypothyroidism (HT) among childhood cancer survivors by means of register
      linkage. Patients extracted from the Finnish Cancer Registry data base (5,180
      patients with cancer diagnosis at the age of 0-15 years, and born after 1970)
      were linked with thyroxin reimbursement data (Drug Reimbursement Register) and
      with thyroxin purchase data (prescription database) maintained by the Social
      Insurance Institution. At the end of follow-up, the prevalence of HT
      (10,509/100,000) was found to exceed that in the general population (240/100,000)
      for those aged <35 years. Diagnostic group (p < 0.0001) and gender (p < 0.0025)
      had significant effect on the risk of developing HT. Males were less prone to the
      development of HT. Cumulative incidence rate of HT was highest in patients with
      thyroid cancer (TC), Hodgkin lymphoma, central nervous system (CNS) tumors and
      neuroblastoma. Except in patients with TC (4.5 months) and CNS tumors (19
      months), the median time for the appearance of HT was quite long, varying between
      2 and 4.5 years. We consider our results valuable in providing new data for the
      planning of thyroid function follow-up in different diagnostic groups of
      childhood cancer survivors.

PMID- 18076069
TI  - BAC array CGH distinguishes mutually exclusive alterations that define
      clinicogenetic subtypes of gliomas.
AB  - The pathological classification of gliomas constitutes a critical step of the
      clinical management of patients, yet it is frequently challenging. To assess the
      relationship between genetic abnormalities and clinicopathological
      characteristics, we have performed a genetic and clinical analysis of a series of
      gliomas. A total of 112 gliomas were analyzed by comparative genomic
      hybridization on a BAC array with a 1 megabase resolution. Altered regions were
      identified and correlation analysis enabled to retrieve significant associations
      and exclusions. Whole chromosomes (chrs) 1p and 19q losses with centromeric
      breakpoints and EGFR high level amplification were found to be mutually
      exclusive, permitting identification of 3 distinct, nonoverlapping groups of
      tumors with striking clinicopathological differences. Type A tumors with chrs 1p
      and 19q co-deletion exhibited an oligodendroglial phenotype and a longer patient
      survival. Type B tumors were characterized by EGFR amplification. They harbored a
      WHO high grade of malignancy and a short patient survival. Finally, type C tumors
      displayed none of the previous patterns but the presence of chr 7 gain, chr 9p
      deletion and/or chr 10 loss. It included astrocytic tumors in patients younger
      than in type B and whose prognosis was highly dependent upon the number of
      alterations. A multivariate analysis based on a Cox model shows that age, WHO
      grade and genomic type provide complementary prognostic informations. Finally,
      our results highlight the potential of a whole-genome analysis as an additional
      diagnostic in cases of unclear conventional genetic findings.

PMID- 18076070
TI  - Gefitinib prevents cancer progression in mice expressing the activated rat
      HER2/neu.
AB  - We tested the efficacy of gefitinib in the prevention of HER2/neu-mediated breast
      cancer development in BALB-NeuT transgenic mice. Oral administration of gefitinib
      to female transgenic mice from 5 to 14 weeks of age reduced tumor multiplicity
      from 9.6 +/- 0.82 to 0.58 +/- 1.1 (83%). We observed a decrease in the number and
      size of lobules and lobular nodules in treated mice with a reduction in the
      overall disease burden per gland. Normal duct development in the mammary glands
      was not affected by gefitinib. The development of acinic cell carcinoma in the
      parotid glands of these animals was also reduced coincident with decreased
      stromal involvement during progression. Gefitinib eliminated phosphorylation of
      HER2 and HER3 and signaling through MAPK and Akt in lobular hyperplasias and
      carcinomas. At the same time MAPK activity and cytokine production in splenocytes
      and lymph nodes was increased in gefitinib-treated animals coincident with an
      increase in lymph node size. Delaying gefitinib treatment until mammary glands
      exhibited atypical lobular hyperplasias reduced efficacy. These studies
      demonstrate the critical role of HER2 signal transduction in the onset and
      progression of HER2/neu-dependent breast cancer and suggest a role for specific
      inhibitors to prevent the outgrowth of early hyperplastic disease.

PMID- 18076071
TI  - Nitroxyl inhibits breast tumor growth and angiogenesis.
AB  - Nitroxyl (HNO) can inhibit the glycolytic enzyme glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH). Because of the importance of glycolysis in many malignant
      cells, we thus propose that HNO can adversely affect tumor growth. This
      hypothesis was tested using in vitro and in vivo models of breast cancer. We
      report here for the first time that HNO suppresses the proliferation of both
      estrogen receptor (ER)-positive and ER-negative human breast cancer cell lines,
      in a dose dependent manner. Mice treated with HNO either injected into the tumor
      itself or via the intraperitoneal approach had smaller xenograft tumor size. In
      addition to significantly decreased blood vessel density in the HNO-treated
      tumors, we observed lower levels of circulating serum vascular endothelial growth
      factor (VEGF). Accordingly, there was a decrease in total HIF-1alpha (hypoxia
      inducible factor) protein in HNO-treated tumor cells. Further studies showed
      inhibition of GAPDH activity in HNO-treated human breast cancer cell lines and in
      HNO-treated tumor tissue derived from xenografts. One explanation for the
      multiplicity of actions observed after HNO treatment could be the effect from the
      initial inhibition of GAPDH, providing a potential therapeutic avenue based upon
      blocking glycolysis resulting in decreased HIF-1alpha, thus leading to
      angiogenesis inhibition. Therefore, HNO appears to act via mechanism(s) different
      from those of existing breast cancer drugs, making it a potential candidate to
      overcome known and emerging drug resistance pathways.

PMID- 18076072
TI  - Birth-related characteristics, congenital malformation, maternal reproductive
      history and neuroblastoma: the ESCALE study (SFCE).
AB  - Since neuroblastoma occurs very early in children's lives, it has been
      hypothesized that pre- and perinatal factors may play a role in its etiology.
      This study investigated the role of birth characteristics, congenital
      malformation and maternal reproductive history in neuroblastoma. The data used
      were generated by the national population-based case-control study, ESCALE,
      conducted in France in 2003-2004. The mothers of 191 neuroblastoma cases and
      1,681 controls, frequency-matched by age and gender, were interviewed by
      telephone, using a standardized questionnaire, on several factors including
      pregnancy, medical history, lifestyle, childhood medical conditions and
      exposures. A positive association between congenital malformation and all
      neuroblastoma cases was observed [Odds ratio (OR) = 2.2, 95% confidence interval
      (95% CI): 1.1-4.5]. Congenital malformations were highly associated to
      neuroblastoma in children aged less than 1 year (OR = 16.8, 95% CI: 3.1-90),
      while no association was observed in children aged 1 year or more (OR = 1.0, 95%
      CI: 0.3-2.9). A negative association with a maternal history of spontaneous
      abortions was also found (OR = 0.6, 95% CI: 0.4-0.9). The results strongly
      support the hypothesis that congenital anomalies may be associated with
      neuroblastoma, particularly in infant (less than 1 year of age).

PMID- 18076073
TI  - Locally generated VGVAPG and VAPG elastin-derived peptides amplify melanoma
      invasion via the galectin-3 receptor.
AB  - Melanomas containing more elastin are associated with higher stages of the
      disease. The interaction between elastin-derived peptides and melanoma cells
      appears to play an important role in the progression of melanomas. The effects of
      the elastin-derived peptides VGVAPG and VAPG have been investigated on the
      migration, invasion, adhesion and angiogenesis of human melanoma cells of
      different invasive potential. Elastin, tropoelastin and VGVAPG peptide were
      demonstrated at the invasion site of melanoma using histochemistry and
      immunohistochemistry. Not only the VGVAPG elastin-derived peptide, which exhibits
      the XGXXPG consensus sequence in its primary structure, but also the shorter VAPG
      bind directly to 3 cell surface receptors: galectin-3, integrin alpha v beta 3
      and elastin-binding protein. Our results suggest that the increased levels of
      elastin-derived peptides facilitate the invasion of melanoma cells: (i) VGVAPG
      and VAPG elastin-derived peptides are chemotactic for melanoma cells; (ii) they
      can increase the migration of melanoma cells and the expression of CXCR-4 and
      CXCL-12 chemokines; (iii) they enhance the expression of the elastin-degrading
      MMP-2 and MMP-3; (iv) they increase the attachment of melanoma cells and the
      expression of different adhesion molecules; (v) they increase the expression of
      the lymphangiogenic VEGF-C and (vi) the galectin-3 receptor can mediate all these
      effects. Clinical and therapeutic aspects are also discussed.

PMID- 18076074
TI  - Effect of surface conjugation chemistry on the sensitivity of microcantilever
      sensors.
AB  - Microcantilever sensors are an offshoot of atomic force microscopy and are useful
      tools for effectively detecting a target biomolecule. The recognition of the
      target molecule on the biosensor is based on the physical bending of the
      microcantilever, which is driven by a specific molecular interaction between the
      target molecule and the sensor surface. In this study, to enhance the sensitivity
      of the microcantilever sensor, the sensor surface was modified through a surface
      conjugation method using self-assembled monolayers (SAMs) and heterobifunctional
      cross-linkers. After the surface modification of the microcantilever sensor, the
      sensitivity for L-cysteine was recorded. The detection of L-cysteine was
      influenced by the active site and the molecular size of the cross-linked compound
      attached onto the surface of the microcantilever.

PMID- 18076075
TI  - Crystal structure of human cyclophilin D in complex with its inhibitor,
      cyclosporin A at 0.96-A resolution.

PMID- 18076076
TI  - Crystal structure of human cellular retinol-binding protein II to 1.2 A
      resolution.

PMID- 18076077
TI  - Solvent-exposed residues located in the beta-sheet modulate the stability of the
      tetramerization domain of p53--a structural and combinatorial approach.
AB  - The role of hydrophobic amino acids in the formation of hydrophobic cores as one
      of the major driving forces in protein folding has been extensively studied.
      However, the implication of neutral solvent-exposed amino acids is less clear and
      available information is scarce. We have used a combinatorial approach to study
      the structural relevance of three solvent-exposed residues (Tyr(327), Thr(329),
      and Gln(331)) located in thebeta-sheet of the tetramerization domain of the tumor
      suppressor p53 (p53TD). A conformationally defined peptide library was designed
      where these three positions were randomized. The library was screened for
      tetramer stability. A set of p53TD mutants containing putative stabilizing or
      destabilizing residue combinations was synthesized for a thermodynamic
      characterization. Unfolding experiments showed a wide range of stabilities, with
      T(m) values between 27 and 83 degrees C. Wild type p53TD and some highly
      destabilized and stabilized mutants were further characterized. Thermodynamic and
      biophysical data indicated that these proteins were folded tetramers, with the
      same overall structure, in equilibrium with unfolded monomers. An NMR study
      confirmed that the main structural features of p53TD are conserved in all the
      mutants analyzed. The thermodynamic stability of the different p53TD mutants
      showed a strong correlation with parameters that favor formation and
      stabilization of the beta-sheet. We propose that stabilization through
      hydrophobic interactions of key secondary structure elements might be the
      underlying mechanism for the strong influence of solvent-exposed residues in the
      stability of p53TD.

PMID- 18076078
TI  - Binding of sulfonium-ion analogues of di-epi-swainsonine and 8-epi-lentiginosine
      to Drosophila Golgi alpha-mannosidase II: the role of water in inhibitor binding.
AB  - Retaining glycosidases operate by a two-step catalytic mechanism in which the
      transition states are characterized by buildup of a partial positive charge at
      the anomeric center. Sulfonium-ion analogues of the naturally occurring
      glycosidase inhibitors, swainsonine and 8-epi-lentiginosine, in which the
      bridgehead nitrogen atom is replaced by a sulfonium-ion, were synthesized in
      order to test the hypothesis that a sulfonium salt carrying a permanent positive
      charge would be an effective glycosidase inhibitor. Initial prediction based on
      computational docking indicated three plausible binding modes to Drosophila Golgi
      alpha-mannosidase II (dGMII), the most likely being close to that of swainsonine.
      Observation of the binding of di-epi-thioswainsonine and 8-epi-thiolentiginosine
      to dGMII from crystallographic data, however, revealed an orientation different
      from swainsonine in the active site. Screening these two compounds against dGMII
      shows that they are inhibitors with IC(50) values of 2.0 and 0.014 mM,
      respectively. This dramatic difference in affinity between the two compounds,
      which differ by only one hydroxyl group, is rationalized in terms of bound water
      molecules and the water molecule substructure in the active site, as identified
      by comparison of high resolution X-ray crystal structures of several dGMII
      inhibitor complexes.

PMID- 18076080
TI  - Early afferent signaling in the outer plexiform layer regulates development of
      horizontal cell morphology.
AB  - The dendritic patterning of retinal horizontal cells has been shown to be
      specified by the cone photoreceptor afferents. The present investigation has
      addressed whether this specification is due to visually dependent synaptic
      transmission in the outer plexiform layer or to some other early, pre-visual,
      neural activity. Individually labeled horizontal cells from dark-reared mice, as
      well as from mice carrying a mutation in the Cacna1f gene, which encodes the pore
      forming calcium channel subunit Ca(v)1.4, were assessed for various morphological
      features. The dark-reared mice showed no alteration in any of these features,
      despite showing a compromised maximal voltage response in the electroretinograms.
      The retinas of Cacna1f mutant mice, by contrast, showed conspicuous morphological
      changes that mimicked the effects observed previously in coneless transgenic
      mice. These changes were present as early as postnatal day 10, when the shape and
      density of the cone pedicles appeared normal. Ultrastructurally, however, the
      pedicles at this early stage, as well as in maturity, lacked synaptic ribbons and
      the invaginations associated with postsynaptic processes. These results suggest a
      role for this calcium channel subunit in ribbon assembly in addition to its role
      in modulating calcium influx and glutamate release. Together, they suggest a
      complex cascade of interactions between developing cone pedicles and horizontal
      cell dendrites involving early spontaneous activity, dendritic attraction, ribbon
      assembly, and pedicle invagination.

PMID- 18076081
TI  - Regenerating motor bridge axons refine connections and synapse on lumbar
      motoneurons to bypass chronic spinal cord injury.
AB  - To restore motor control after spinal cord injury requires reconnecting the brain
      with spinal motor circuits below the lesion. A bridge around the injury is an
      important alternative to promoting axon regeneration through the injury.
      Previously, we reported a novel motor bridge in rats. The thirteenth thoracic
      nerve was detached from the muscle it innervates and the cut end implanted
      caudally into the lumbar gray matter where motor bridge axons regenerate. In this
      study, we first determined that regenerating bridge axons project to spinal motor
      circuits. Stable projections were present in ventral motor laminae of the cord,
      including putative synapses directly on motoneurons, 2 months after insertion in
      the intact cord. At this time, earlier-forming dorsal horn projections were
      mostly eliminated. Regenerating axons were effective in evoking leg motor
      activity as early as 2 weeks. We next determined that bridge axons could
      regenerate caudal to a chronic injury. We hemisected the spinal cord at L2 and
      inserted the bridge nerve 1 month later at L5 and found ventral laminae
      projections similar to those in intact animals, including onto motoneurons
      directly. Finally, we determined that the bridge circuit could be activated by
      neural pathways rostral to its origin. For spinally hemisected animals, we
      electrically stimulated the rostral spinal cord and recorded evoked potentials
      from the bridge and, in turn, motor responses in the sciatic nerve. Our findings
      suggests that bridge motoneurons could be used by descending motor pathways as
      premotor interneurons to transmit neural signals to bypass a chronic spinal
      injury.

PMID- 18076082
TI  - Sexual dimorphism in neuronal number of the posterodorsal medial amygdala is
      independent of circulating androgens and regional volume in adult rats.
AB  - The posterodorsal medial amygdala (MePD) in rodents integrates olfactory and
      pheromonal information, which, coupled with the appropriate hormonal signals, may
      facilitate or repress reproductive behavior in adulthood. MePD volume and
      neuronal soma size are greater in male rats than in females, and these sexual
      dimorphisms are maintained by adult circulating hormone levels. Castration of
      adult males causes these measures to shrink to the size seen in females 4 weeks
      later, whereas testosterone treatment of adult females for 4 weeks enlarges these
      measures to the size of males. We used stereological methods to count the number
      of cells in the MePD and found that, in addition to the sex difference in
      regional volume and soma size, males also have more MePD neurons than do females,
      yet these numbers are unaffected by the presence or absence of androgen in adults
      of either sex. Males also have more glial cells than do females, but, in contrast
      to the effects on neuronal number, the number of glial cells is affected by
      androgen in the right MePD of both sexes and, therefore, may contribute to
      regional volume changes in adulthood in that hemisphere. Thus, regional volume,
      neuronal size, and glial numbers vary in the MePD of adult rats in response to
      circulating androgens, but neuronal number does not. These results suggest that
      the sex difference in neuronal number in the rat MePD may be "organized" by
      androgens prior to adulthood, whereas regional volume, neuronal size, and glial
      numbers can be altered by androgens in adulthood.

PMID- 18076083
TI  - Anatomical and physiological definition of the motor cortex of the marmoset
      monkey.
AB  - We used a combination of anatomical and physiological techniques to define the
      primary motor cortex (M1) of the marmoset monkey and its relationship to adjacent
      cortical fields. Area M1, defined as a region containing a representation of the
      entire body and showing the highest excitability to intracortical
      microstimulation, is architecturally heterogeneous: it encompasses both the
      caudal part of the densely myelinated "gigantopyramidal" cortex (field 4) and a
      lateral region, corresponding to the face representation, which is less
      myelinated and has smaller layer 5 pyramidal cells (field 4c). Rostral to M1 is a
      field that is strongly reminiscent of field 4 in terms of cyto- and
      myeloarchitecture but that in the marmoset is poorly responsive to
      microstimulation. Anatomical tracing experiments revealed that this rostral field
      is interconnected with visual areas of the posterior parietal cortex, whereas M1
      itself has no such connections. For these reasons, we considered this field to be
      best described as part of the dorsal premotor cortex and adopted the designation
      6Dc. Histological criteria were used to define other fields adjacent to M1,
      including medial and ventral subdivisions of the premotor cortex (fields 6M and
      6V) and the rostral somatosensory field (area 3a), as well as a rostral
      subdivision of the dorsal premotor area (field 6Dr). These results suggest a
      basic plan underlying the histological organization of the caudal frontal cortex
      in different simian species, which has been elaborated during the evolution of
      larger species of primate by creation of further morphological and functional
      subdivisions.

PMID- 18076085
TI  - Cellular and subcellular localization of Kir2.1 subunits in neurons and glia in
      piriform cortex with implications for K+ spatial buffering.
AB  - Potassium channels of the Kir2 family are widely expressed in neurons and glia,
      where they form strong inwardly rectifying channels. Existing functional
      hypotheses for these channels in neurons are based on the weak outward
      conductance, whereas the leading hypothesis for glia, that they promote potassium
      spatial buffering, is based on inward conductance. Although the spatial buffering
      hypothesis has been confirmed for Muller glia in retina, many aspects of Kir2
      channels that will be required for understanding their functional roles in
      neurons and other forms of glia have received little or no study. Particularly
      striking is the paucity of data regarding their cellular and subcellular
      localization. We address this gap for Kir2.1-containing channels by using light
      and electron microscopic immunocytochemistry. The analysis was of piriform
      cortex, a highly epileptogenic area of cerebral cortex, where pyramidal cells
      have K(+)-selective strong inward rectification like that observed in Muller
      cells, where Kir2.1 is the dominant Kir2 subunit. Pyramidal cells in adult
      piriform cortex also lack I(h), the mixed Na(+)-K(+) current that mediates a
      slower form of strong inward rectification in large pyramidal cells in neocortex
      and hippocampus. The experiments demonstrated surface expression of Kir2.1
      containing channels in astrocytes and in multiple populations of pyramidal and
      nonpyramidal cells. Findings for astrocytes were not consistent with predictions
      for K(+) spatial buffering over substantial distance. However, findings for
      pyramidal cells suggest that they could be a conduit for spatially buffering K(+)
      when it is highly elevated during seizure.

PMID- 18076086
TI  - Characterization of nitric oxidergic neurons in the alimentary tract of the snail
      Helix pomatia L.: histochemical and physiological study.
AB  - By using NADPH-diaphorase (NADPH-d) histochemistry, nitric oxide synthase (NOS)
      immunohistochemistry, Western blotting, and NO pharmacology, we investigated the
      distribution and possible function of NOS-containing neurons in different units
      of the alimentary tract of the snail, Helix pomatia. Discrete populations of
      neurons in the buccal ganglia displayed NADPH-d reactivity. NADPH-d-reactive and
      NOS-immunoreactive (NOS-IR) neurons were present in the caecum, and labeled
      fibers were found to innervate the circular muscles of the proesophagus and
      caecum and to form axosomatic connections with neurons of the myenteric and
      submucosal plexi of the caecum. A 65-kDa protein was found to be nNOS-IR in the
      caecum protein extract. The majority of the NADPH-d-reactive neurons also
      displayed FMRFamide immunoreactivity, whereas a mutual innervation by NADPH
      diaphorase-reactive and catch-relaxing peptide (CARP)-IR neurons was observed in
      the caecum. Application of NO-donors [glyceryl trinitrate, S-nitroso-N-acetyl-DL
      penicillamine, sodium nitroprusside (SNP)] evoked a dose-dependent increase in
      tension, frequency, and amplitude of the spontaneous muscle contractions of the
      proesophagus and caecum. Contractions could be blocked by applying the NO
      scavenger 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide. FMRFamide
      evoked a response of the caecum similar to that with NO, and its simultaneous
      application was additive. Preincubation with CARP blocked the increase of tension
      evoked by SNP, whereas Mytilus inhibitory peptide (MIP) decreased the rhythmic
      contractions induced by the NO donor. Our findings indicate that NO is an
      important signal molecule in the feeding system of Helix, involved, partially in
      cooperation with different molluscan neuropeptides, in the regulation of both
      neuronal and muscular activities.

PMID- 18076087
TI  - Significance of age in acute myeloid leukemia patients younger than 30 years: a
      common analysis of the pediatric trials AML-BFM 93/98 and the adult trials AMLCG
      92/99 and AMLSG HD93/98A.
AB  - BACKGROUND: Data on the impact of age in acute myeloid leukemia (AML) patients
      <30 years treated in pediatric and adult trials are scarce. METHODS: In all, 891
      patients <18 years were treated in the pediatric trials AML-BFM 93/98 and 290
      adolescents and young adults (>16 to <30 years) in the AMLCG 92/99 and AMLSG
      HD93/98A trials. Treatment schedules and dose intensities were comparable.
      RESULTS: Initial features and risk factors differed considerably between infants
      (<2 years) and older age groups and only slightly between children (2 to <13),
      adolescents (13 to <21) and young adults (21 to <30). Treatment results were most
      favorable in children (5-year event free survival [EFS]: 54% +/- 3%), slightly
      inferior in adolescents (46% +/- 4%, P = .03), and unfavorable in young adults
      (28% +/- 5%, P = .0001). Excluding patients with favorable karyotypes, the
      results were similar in infants and children (EFS: 44% +/- 4% and 46% +/- 3%,
      respectively) and inferior in adolescents (35% +/- 4%) and young adults (23% +/-
      4%). There was an increased, age-related percentage and inferior outcome in
      patients with >5% bone marrow blasts after induction. EFS was especially poor in
      young adults, with blasts >5%. The blast count after induction was of no
      prognostic value in patients with favorable karyotypes, but a significant risk
      factor in patients with other cytogenetics. CONCLUSIONS: Biologic data differed
      mainly between infants and older age groups. When comparing the same age groups,
      outcome was similar between the trial groups, which differed from reports
      concerning acute lymphoblastic leukemia. However, the prognosis decreased after
      childhood independent of other risk factors. This indicates that even in the
      younger cohorts increasing age may be an additional unfavorable factor.

PMID- 18076084
TI  - Predictors of deterioration in health-related quality of life in Parkinson's
      disease: results from the DATATOP trial.
AB  - The aim of this study was to investigate factors associated with decline in
      health-related quality of life in Parkinson's disease, by a retrospective cohort
      study from referral centers in Canada and the United States. Subjects were
      patients with early Parkinson's disease (N = 362) enrolled in a clinical trial of
      deprenyl (selegiline) and tocopherol (DATATOP) and followed prospectively. The
      main outcome measure was change in health-related quality of life using SF-36
      Mental and Physical Component Summary scores. The mean interval between SF-36
      measurements was 1.7 +/- 0.1 years, beginning 5 to 6 years after enrolment into
      the trial. In multivariable analysis, baseline Hamilton Depression Scale scores
      and self-rated cognitive function were associated with subsequent decline in
      Physical Component Summary scores, while older age and Schwab and England
      activities of daily living scores were associated with decline in Mental
      Component Summary scores. The Postural Instability Gait Disorder score was the
      only variable found to decline concurrently with HRQOL. Our results suggest that
      depression, self-rated cognitive function, and one's degree of functional
      independence are predictors of subsequent changes in HRQOL. Our focus in clinical
      care needs to be broadened beyond assessing and treating Parkinsonism,
      recognizing the impact of mood, cognition and function on HRQOL.

PMID- 18076088
TI  - English and Spanish versions of the Body Shape Questionnaire: measurement
      equivalence across ethnicity and clinical status.
AB  - OBJECTIVE: We evaluated the psychometric properties and measurement equivalence
      of various forms of the Body Shape Questionnaire (BSQ) (Cooper et al., Int J Eat
      Disord, 6, 485-494, 1987) in American and Spanish women with and without an
      eating disorder diagnosis. METHOD: Participants included four groups of women:
      Euro-American (n = 505), Hispanic-American (n = 151), and Spanish (n = 445)
      females without an eating disorder and Spanish women being treated for an eating
      disorder (n = 177). RESULTS: Single and multigroup confirmatory factor analyses
      using maximum likelihood estimation with robust standard errors tested the data
      for configural and metric invariance. Goodness-of-fit statistics indicated that
      the original and all alternate forms of the BSQ fit the data well across groups.
      Most factor loadings were similar across groups. We also developed a 10-item
      version that appeared to be invariant across groups. CONCLUSION: Results strongly
      support configural invariance and offer some support for metric invariance.

PMID- 18076089
TI  - A systemic approach toward optimization of the hot embossing of poly-L-lactic
      acid for biomedical applications.
AB  - Poly L-lactic acid (PLLA) is a popular biodegradable polymer that is used
      extensively for many biological applications. A limitation of using PLLA is the
      difficulty in forming the polymer in complex shapes and forms for applications
      that include drug delivery and tissue engineering. This study focuses on PLLA
      replication using hot embossing technology. In this study hot embossing process
      parameters were identified, replication quality was examined, and crystallinity
      of PLLA was analyzed. The replication quality of micropillars and microreservoirs
      was examined using optical microscopy and scanning electron microscopy, with good
      replication obtained using a hot embossing pressure of 18 MPa at a temperature of
      85 degrees C and holding time of 120 s. The material properties were examined
      using differential scanning calorimetry and infrared spectroscopy that indicated
      no substantial crystallinity or structural changes during hot embossing of PLLA.
      The study presented in this article concludes with the assessment that hot
      embossing technology could be used as a viable micromanufacturing process for the
      fabrication of inexpensive PLLA-based microdevices, with possible applications to
      controlled drug delivery, growth factors pathways, or other therapeutic
      applications.

PMID- 18076090
TI  - Sustained release of complexed and naked DNA from polymer films.
AB  - Controlled release studies of DNA from polymers have been limited, with most
      studies concentrating on microsphere formulations. This report details a study
      done on the release and transfection efficiencies of pDNA-lipofectamine complex
      (lipoplex), from selected polymeric films in which it was dispersed; the release
      and transfection efficiency was compared with that of naked pDNA. A biodegradable
      and a biostable polymer were compared. A sustained release profile was obtained
      from both the polymeric films. For the release of pDNA (naked DNA), a burst
      effect was always seen, and was suppressed using additives; for complexed pDNA
      (lipoplex), the release was slow, but could be accelerated using additives. The
      compositions of the released lipoplexes were also quantified in terms of the
      fraction that was complexed. In addition, the transfection efficiency of the
      released complexes and of the naked pDNA was determined in vitro using COS 7
      cells. The results also demonstrated that bioactivity of the released complexed
      pDNA was superior to that of the released naked DNA. Such formulations may be
      useful for local sustained delivery of lipoplexes from implanted films.

PMID- 18076091
TI  - In vitro cytotoxicity of dental alloys and cpTi obtained by casting.
AB  - BACKGROUND: This study aimed to compare the cytotoxicity of base-metal dental
      alloys and to evaluate if the casting method could influence their cytotoxicity.
      METHODS: Disks of base-metal dental alloys were cast by two methods: plasma,
      under argon atmosphere, injected by vacuum-pressure; and oxygen-gas flame,
      injected by centrifugation, except Ti-6Al-4V and commercially pure titanium
      (cpTi), cast only by plasma. SCC9 cells were cultured in culture media D
      MEM/Ham's F12 supplemented, at 37 degrees C in a humidified atmosphere of 5%
      carbon dioxide and 95% air, on the previously prepared disks. At subconfluence in
      wells without disks (control), cell number and viability were evaluated. RESULTS:
      In plasma method, cpTi and Ti-6Al-4V were similar to control and presented higher
      number of cells than all other alloys, followed by Ni-Cr. In oxygen-gas flame
      method, all alloys presented fewer cells than control. Ni-Cr presented more cells
      than any other alloy, followed by Co-Cr-Mo-W which presented more cells than Ni
      Cr-Ti, Co-Cr-Mo, and Ni-Cr-Be. There were no significant differences between
      casting methods related to cell number. Cell viability was not affected by either
      chemical composition or casting methods. CONCLUSION: cpTi and Ti-6Al-4V were not
      cytotoxic while Ni-Cr-Be was the most cytotoxic among tested alloys. The casting
      method did not affect cytotoxicity of the alloys.

PMID- 18076092
TI  - In vitro biostability evaluation of polyurethane composites in acidic, basic,
      oxidative, and neutral solutions.
AB  - New and improved properties can often be achieved by compounding two or more
      different but compatible materials. But, can failure possibility also be
      increased by such a compounding strategy? In this article, we compared the in
      vitro biostability of composites with that of the pure polymer. We tested three
      model composites in oxidative, acidic, basic, and neutral solutions. We found
      that oxidation degradation was much more profound in the composites than in the
      corresponding pure polymer. This degradation seemed to be an intrinsic property
      of composite materials. We also observed the well documented interfacial
      debonding between filler and matrix and its effects on the mechanical
      reinforcement of the hydrated composites. The improvements in acid and base
      resistance were also observed.

PMID- 18076093
TI  - Novel 3D collagen scaffolds fabricated by indirect printing technique for tissue
      engineering.
AB  - This article reports the mechanical properties and in vitro evaluation of a
      collagen scaffold fabricated using an indirect 3D printing technique. Collagen
      scaffolds, featuring predefined internal channels and capillary networks, were
      manufactured using phase change printing. It was observed that the collagen
      scaffolds featured internal channels and a hierarchical structure that varied
      over length scales of 10-400 microm. In vitro evaluation using hMSCs demonstrated
      that the resultant collagen based scaffolds have the ability to support hMSC cell
      attachment and proliferation; cells can migrate and survive deep within the
      structure of the scaffold. The cell numbers increased 2.4 times over 28 days in
      culture for the lysine treated scaffolds. The cells were spread along the
      collagen fibers to form a 3D structure and extracellular matrix was detected on
      the surface of the scaffolds after 4 weeks in culture. The crosslinking treatment
      enhanced the biostability and dynamic properties of the collagen scaffolds
      significantly.

PMID- 18076094
TI  - Tissue-engineered blood vessels with endothelial nitric oxide synthase activity.
AB  - Nondegradable synthetic polymer vascular grafts used in cardiovascular surgery
      have shown serious shortcomings, including thrombosis, calcification, infection,
      and lack of growth potential. Tissue engineering of vascular grafts with
      autologous stem cells and biodegradable polymeric materials could solve these
      problems. The present study is aimed to develop a tissue-engineered vascular
      graft (TEVG) with functional endothelium using autologous bone marrow-derived
      cells (BMCs) and a hybrid biodegradable polymer scaffold. Hybrid biodegradable
      polymer scaffolds were fabricated from poly(lactide-co-epsilon-caprolactone)
      (PLCL) copolymer reinforced with poly(glycolic acid) (PGA) fibers. Canine bone
      marrow mononuclear cells were induced in vitro to differentiate into vascular
      smooth muscle cells and endothelial cells. TEVGs (internal diameter: 10 mm,
      length: 40 mm) were fabricated by seeding vascular cells differentiated from BMCs
      onto PGA/PLCL scaffolds and implanted into the abdominal aorta of bone marrow
      donor dogs (n = 7). Eight weeks after implantation of the TEVGs, the vascular
      grafts remained patent. Histological and immunohistochemical analyses of the
      vascular grafts retrieved at 8 weeks revealed the regeneration of endothelium and
      smooth muscle and the presence of collagen. Western blot analysis showed that
      endothelial nitric oxide synthase (eNOS) was expressed in TEVGs comparable to
      native abdominal aortas. This study demonstrates that vascular grafts with
      significant eNOS activity can be tissue-engineered with autologous BMCs and
      hybrid biodegradable polymer scaffolds.

PMID- 18076095
TI  - Effects of compaction pressure and particle shape on the porosity and compression
      mechanical properties of sintered Ti6Al4V powder compacts for hard tissue
      implantation.
AB  - Sintered Ti6Al4V powder compacts potentially to be used in implant applications
      were prepared using commercially available spherical and angular powders (100-200
      mum) within the porosity range of 34-54%. Cylindrical green powder compacts were
      cold compacted at various pressures and then sintered at 1200 degrees C for 2 h.
      The final percent porosity and mean pore sizes were determined as functions of
      the applied compaction pressure and powder type. The mechanical properties were
      investigated through compression testing. Results have shown that yield strength
      of the powder compacts of 40-42% porosity was comparable with that of human
      cortical bone. As compared with previously investigated Ti powder compacts,
      Ti6Al4V powder compacts showed higher strength at similar porosity range.
      Microscopic observations on the failed compact samples revealed that failure
      occurred primarily by the separation of interparticle bond regions in the planes
      45 degrees to the loading axis.

PMID- 18076096
TI  - Architecture of an in vivo-tissue engineered autologous conduit "Biovalve".
AB  - As a practical concept of regenerative medicine, we have focused on in vivo
      tissue engineering utilizing the foreign body reaction. Plastic substrates for
      valvular leaflet organization, consisting of two pieces assembled with a small
      aperture were inserted into a microporous polyurethane conduit scaffold. The
      assembly was placed in the subcutaneous spaces of Japanese white rabbits for 1
      month. After the substrates were pulled out from the harvested implant, valve
      leaflet-shaped membranous tissue was formed inside the tubular scaffold as
      designed. The valve leaflet was composed of the same collagen-rich tissue, with
      the absence of any elastic fiber, as that which had ingrown or covered the
      scaffold. No abnormal collection or infiltration of inflammatory cells in the
      leaflet and the scaffold could be demonstrated. According to the
      immunohistochemical staining, the leaflet was comprised of numerous vimentin- or
      alpha-SMA-positive cells, corresponding to fibroblasts or myofibroblats, but
      contained no desmin-positive cells. The analysis of the video data of the valve
      movement showed that, in synchronization with the backward flow in the diastolic
      phase, the valve closed rapidly and tightly and, in the transition phase of the
      flow direction, the valve opened smoothly without flapping or hitting the
      scaffold wall. Using mold designs, consisting of two different plastic substrates
      and the tubular scaffold, in conjunction with "in body tissue architecture," the
      complex 3-dimensional autologous conduit-typed Biovalve was developed for the
      first time.

PMID- 18076097
TI  - Effect of low intensity pulsed ultrasound on healing of an ulna defect filled
      with a bone graft substitute.
AB  - A 1.5 cm unilateral rabbit ulna defect model was performed in 18 adult NZ white
      rabbits. The defects were filled with a beta-tricalcium phosphate bone graft
      substitute (JAX TCP). The surgical site in half the animals was treated daily
      with 20 min of low intensity pulsed ultrasound (LIPUS). Animals were sacrificed
      at 4 weeks (n = 3 per group) or 12 weeks (n = 6 per group) following surgery for
      radiographic and histologic endpoints. Radiography revealed some resorption of
      the JAX TCP by 12 weeks in the control and LIPUS treated groups. LIPUS treatment
      did not accelerate this resorption. Some new bone formation was noted in the
      control groups at the defect margins while little bone formed in the center of
      the defect at 4 and 12 weeks. In contrast, radiographs revealed more new bone at
      4 and 12 weeks in the LIPUS treated animals throughout the section. Bone mineral
      density (DEXA) revealed a statistically significant difference at 4 weeks with
      LIPUS while no differences were found at 12 weeks. Histology of the LIPUS treated
      sections demonstrated new woven bone formation on and between the JAX TCP bone
      graft substitute particles across the defect. VEGF expression was increased with
      LIPUS treatment at 4 weeks and remained elevated at 12 weeks compared with
      controls. CBFA-1 expression levels were elevated with LIPUS treatment at both
      time points. LIPUS treatment increased bone formation in ulna defect healing with
      a beta-tricalcium phosphate bone graft substitute.

PMID- 18076098
TI  - Evaluation of the biocompatibility and osteoproductive activity of ostrich
      eggshell powder in experimentally induced calvarial defects in rabbits.
AB  - The purpose of this study was to investigate the beneficial effects of
      particulate ostrich eggshell grafting on the healing of experimentally induced
      skull defects. The clinical, radiological, histological, and histomorphometrical
      findings of this material were compared with the results of commercially
      available demineralized bone matrix (DBM). The study was conducted on 18 adult
      New Zealand rabbits. One defect served as a control and the remaining ones either
      were filled with different sized eggshell particles or DBM, in each animal.
      Clinical and radiological inspections and histologic investigations of the
      animals were done at the 1st, 3rd, and 6th months of postoperative period.
      Radiologically, minimal bone regeneration was observed at the empty, control
      defect sites. The most advanced bone regeneration was in the DBM grafted defects.
      The eggshell particle grafted defect sites displayed weak bone regeneration at
      earlier stages, at 1st and 3rd months after operation when compared with
      demineralized bone matrix. Nevertheless, ossification was satisfactory at 6th
      month after operation when compared with the control defects. Within the
      limitations of this study, it was concluded that Ostrich eggshell powder (OSP) is
      a worth-while bone substitute because it is a safe, cheap, and easily available
      material. Long-term studies will clarify its possible role in maxillofacial
      surgery. Further sophisticated experiments should be undertaken before human
      implantation concerning its osteoproductive activity alone or in combination with
      other materials.

PMID- 18076099
TI  - Cerebroretinal microangiopathy with calcifications and cysts (CRMCC).
AB  - Extensive intracranial calcifications and leukoencephalopathy are seen in both
      Coats plus and leukoencephalopathy with calcifications and cysts (LCC; Labrune
      syndrome). Coats plus syndrome is additionally characterized by the presence of
      bilateral retinal telangiectasia and exudates while LCC shows the progressive
      formation of parenchymal brain cysts. Despite these apparently distinguishing
      features, recent evidence suggests that Coats plus and LCC represent the same
      clinical entity with a common primary pathogenesis involving a small vessel
      obliterative microangiopathy. Here, we describe eight previously unreported
      cases, and present an update on one of the original Coats plus patients to
      highlight the emerging core clinical features of the "cerebroretinal
      microangiopathy with calcification and cysts" (CRMCC) phenotype.

PMID- 18076100
TI  - Acute postnatal cataract formation in Smith-Lemli-Opitz syndrome.
AB  - We report on two patients with severe Smith-Lemli-Opitz syndrome who acutely
      developed postnatal cataracts. These postnatal cataracts appear to be due to a
      different pathological mechanism and have a different clinical course than the
      typical congenital cataracts that occur in SLOS. The rapid development of these
      cataracts suggests that dysfunction or rupture of the lens capsule leading to
      acute osmotic shifts contributes to their formation. In addition, cataract
      formation in these patients was associated with conjunctival injection, fibrotic
      irido-lenticular adhesions, and capsular fibrosis. These findings are suggestive
      an inflammatory component that is consistent with impaired competence of the lens
      capsule.

PMID- 18076101
TI  - Molecular cytogenetic and clinical findings in a patient with a small
      supernumerary r(8) mosaicism.

PMID- 18076102
TI  - Prenatal and postnatal presentation of severe achondroplasia with developmental
      delay and acanthosis nigricans (SADDAN) due to the FGFR3 Lys650Met mutation.
AB  - We present prenatal and postnatal features of a patient with severe
      achondroplasia with developmental delay and acanthosis nigricans (SADDAN).
      Mutation analysis confirmed the clinical diagnosis by detecting the FGFR3
      Lys650Met mutation. This case, one of only six with molecular analysis reported
      in the literature, confirms the severe morbidity and adds to the reports with
      early mortality associated with SADDAN. Clinical-radiological characteristics of
      all reported cases of SADDAN are reviewed and discussed.

PMID- 18076103
TI  - Autosomal dominant transmission of nonsyndromic diastasis recti and weakness of
      the linea alba.

PMID- 18076104
TI  - Multiple hemangiomas in a patient with a t(3q;4p) translocation: an infrequent
      association with Wolf-Hirschhorn syndrome.
AB  - We report on the clinical phenotype of an infant with a duplication of the
      terminal portion of the long arm of chromosome 3(q26.3-qter) and a deletion of
      the terminal portion of the short arm of chromosome 4(p16.3) with multiple
      hemangiomas and a hamartoma. Patients with deletions of distal 4p have the
      characteristic features of Wolf-Hirschhorn syndrome (WHS); whereas those with the
      distal duplication of 3q have a well recognized syndrome with some features
      resembling Cornelia-de Lange syndrome (CdLS). Neither of these recognized
      chromosomal anomalies has been reported previously to be associated with multiple
      hemangiomas or other vascular malformations.

PMID- 18076105
TI  - Phenotype-genotype characterization of alpha-thalassemia mental retardation
      syndrome due to isolated monosomy of 16p13.3.
AB  - An 8-year-old Caucasian girl presented with mild dysmorphic features and
      intellectual disability (ID) affecting multiple spheres. Dysmorphisms included a
      high forehead with up-slanting palpebral fissures, prominent nasal root and
      bridge, flattened maxilla, high-arched palate, and anterior frenulum. Structural
      brain anomalies included reduced periventricular white matter volume and thin
      corpus callosum. The presence of HbH bodies and her clinical presentation raised
      suspicion for autosomal alpha-thalassemia mental retardation syndrome (ATR-16).
      Whole-genome array analysis at 1 Mb resolution was performed, which revealed a
      sub-microscopic loss of 16p involving clones RP11-344L6 at 0.1 Mb, RP1-121I4 at
      0.2 Mb and RP11-334D3 at 1 Mb. FISH confirmed deletion (del) of the terminal
      clone (RP1-121I4) on 16pter, which was de novo in origin. The more proximal clone
      RP11-334D3 (at 1 Mb) showed diminished FISH signal intensity on one of the
      homologues, suggesting that one breakpoint occurred within this clone.
      Quantitative PCR (qPCR) confirmed a de novo deletion encompassing SOX8 (at 0.97
      Mb). ATR-16 is characterized by ID with mild, nonspecific dysmorphic features,
      and is associated with terminal del16p (MIM No. 141750). Cases of isolated
      monosomy for 16p are rarely described; such descriptions help to delineate the
      syndrome in the absence of confounding karyotypic anomalies. We describe detailed
      molecular cytogenetic and clinical findings relating to a subject with ATR-16.

PMID- 18076106
TI  - Mutations in GATA4, NKX2.5, CRELD1, and BMP4 are infrequently found in patients
      with congenital cardiac septal defects.

PMID- 18076107
TI  - Confronting complexity in late-onset Alzheimer disease: application of two-stage
      analysis approach addressing heterogeneity and epistasis.
AB  - Common diseases with a genetic basis are likely to have a very complex etiology,
      in which the mapping between genotype and phenotype is far from straightforward.
      A new comprehensive statistical and computational strategy for identifying the
      missing link between genotype and phenotype has been proposed, which emphasizes
      the need to address heterogeneity in the first stage of any analysis and gene
      gene interactions in the second stage. We applied this two-stage analysis
      strategy to late-onset Alzheimer disease (LOAD) data, which included functional
      and positional candidate genes and markers in a region of interest on chromosome
      10. Bayesian classification found statistically significant clusterings for
      independent family-based and case-control datasets, which used the same five
      markers in leucine-rich repeat transmembrane neuronal 3 (LRRTM3) as the most
      influential in determining cluster assignment. In subsequent analyses to detect
      main effects and gene-gene interactions, markers in three genes--urokinase-type
      plasminogen activator (PLAU), angiotensin 1 converting enzyme (ACE) and cell
      division cycle 2 (CDC2)--were found to be associated with LOAD in particular
      subsets of the data based on their LRRTM3 multilocus genotype. All of these genes
      are viable candidates for LOAD based on their known biological function, even
      though PLAU, CDC2 and LRRTM3 were initially identified as positional candidates.
      Further studies are needed to replicate these statistical findings and to
      elucidate possible biological interaction mechanisms between LRRTM3 and these
      genes.

PMID- 18076108
TI  - Correlation of hemocyte counts with different developmental parameters during the
      last larval instar of the tobacco hornworm, Manduca sexta.
AB  - We determined the changes in hemocyte titer and in the abundance of hemocyte
      types of the tobacco hornworm Manduca sexta during the fourth and fifth larval
      stadium and the beginning of the pupal stadium. As we analyzed the samples of
      individual insects at daily intervals, we were able to correlate phenotypical
      features, body weight, as well as total protein content and lysozyme activity in
      the hemolymph with the observations on hemocytes. In the course of the fifth
      larval stadium, the hemocyte titer decreased slightly and declined further after
      pupation. Using calculated values for total hemocyte numbers, females had about
      five times and males three times more hemocytes in the circulating population at
      the beginning of the wandering stage (in the middle of the fifth larval stadium)
      than immediately after the last larval--larval molt (from the fourth to the fifth
      larval stadium). This sexual difference was mainly due to an increase in the
      number of plasmatocytes, which was more prominent in females than in males.
      Granular cells were dominant in early fifth larval stadium while plasmatocytes
      were the most abundant cells in pupae. Oenocytoids and spherule cells disappeared
      during the wandering stage. Lysozyme activity in the hemolymph rose to a maximum
      during the wandering stage, with females having lysozyme values twice as high as
      those for males. These changes in lysozyme activity, however, did not correlate
      with the increase of total hemolymph protein titer which occurred already at the
      beginning of the wandering stage. We postulate that changes in hemocyte titers
      are under direct hormonal control, which has to be proven in future experiments.

PMID- 18076109
TI  - The DNA puff 4C expresses a salivary secretion protein in Trichosia pubescens
      (Diptera; Sciaridae).
AB  - DNA puffs are genomic regions of polytene chromosomes that undergo
      developmentally controlled DNA amplification and transcription in salivary glands
      of sciarid flies. Here, we tested the hypothesis that DNA puff genes code for
      salivary proteins in Trichosia pubescens. To do that, we generated antibodies
      against saliva and immunoscreened a cDNA library made from salivary glands. We
      isolated clones corresponding to DNA puff regions, including clone D-50 that
      contained the entire coding sequence of the previously isolated C4B1 gene from
      puff 4C. Indeed, we showed that puff 4C is a DNA puff region detecting its local
      transcription and its extra rounds of DNA incorporation compared to neighboring
      regions. We further confirmed D-50 clone identity in Western blots reacted with
      the anti-saliva anitiserum. We detected a recombinant protein expressed by this
      clone that had the expected size for a full-length product of the gene. We end
      with a discussion of the relationship between DNA puff genes and their products.

PMID- 18076110
TI  - Farnesoic acid O-methyl transferase (FAMeT) isoforms: conserved traits and gene
      expression patterns related to caste differentiation in the stingless bee,
      Melipona scutellaris.
AB  - Farnesoic acid O-methyl transferase (FAMeT) is the enzyme that catalyzes the
      formation of methyl farnesoate (MF) from farnesoic acid (FA) in the biosynthetic
      pathway of juvenile hormone (JH). This work reports the cloning, sequencing, and
      expression of FAMeT gene from the stingless bee Melipona scutellaris (MsFAMeT).
      The MsFAMeT in silico analysis showed that greatest sequence similarity is found
      in Apis mellifera and other insects, while relatively less similarity is shown in
      crustaceans. Evidence of alternative splicing of a 27 nucleotide (nt) microexon
      explains the presence of the detected isoforms, 1 and 2. The expression analysis
      of the two isoforms showed a marked difference when castes were compared,
      suggesting that they could be involved differently in the JH metabolism in M.
      scutellaris, providing new insights for the comprehension of female plasticity.

PMID- 18076111
TI  - Functional analysis of four Gloverin-like genes in the silkworm, Bombyx mori.
AB  - To identify genes involved in the innate immunity of the silkworm Bombyx mori, we
      constructed a cDNA library from the fat body of Escherichia coli-challenged B.
      mori larvae. Based on the expressed sequence tag (EST) data and whole genome
      shotgun sequence analysis, we found four Gloverin-like genes, BmGlov1-4, in the
      Bombyx genome. Northern blot and RT-PCR analysis showed that BmGlov1-4 were
      induced in the larval fat body after an immune challenge by the injection of E.
      coli; however, less induction was observed after the injection of a yeast Candida
      albicans. In silico sequence analysis revealed the presence of a motif homologous
      to NF-kappaB binding site in the upstream region of each BmGlov gene. Moreover,
      we expressed recombinant BmGlov1-4 proteins using the baculovirus expression
      system, and found that all the recombinant BmGlov1-4 significantly inhibited the
      growth of E. coli.

PMID- 18076112
TI  - A prospective study of delusional misidentification syndromes in Parkinson's
      disease with dementia.
AB  - Delusional misidentification syndromes (DMS) are a group of neuropsychiatric
      disorders due to disturbances in familiarity. DMS in organic diseases have been
      related to deficits in executive, memory, and visuospatial function. DMS are
      frequently reported in dementia with Lewy bodies (DLB). The presence of DMS in
      Parkinson's disease with dementia (PDD), which shares similar clinical and
      neuropsychological features with DLB, has not been studied. We describe the
      frequency and clinical features of DMS in a cohort of PDD patients, and we
      compare the neuropsychological profile between PDD patients with and without DMS.
      Prospective study of 30 PDD patients recruited from an outpatient setting, who
      received a structured behavioral interview assessing DMS and hallucinations, and
      a neuropsychological battery assessing executive function, memory, language, and
      visuospatial abilities. DMS were found in 16.7% of PDD patients. All DMS subjects
      also exhibited hallucinations that were significantly more severe than in PDD
      without DMS. DMS were responsive to neuroleptic drugs. PDD subjects with DMS
      presented a different neuropsychological profile than PDD subjects without DMS,
      with more severe memory and language deficits, but similar levels of executive
      and visuospatial impairment. DMS is a neuropsychiatric feature associated with
      PDD. Greater impairment in language and memory in PDD with DMS suggests a
      prominent role of the temporal cortex in the genesis of DMS in PDD.

PMID- 18076113
TI  - Neurofibromatosis 1: analysis of the demand for prenatal diagnosis in a French
      cohort of 361 patients.
AB  - The severity of neurofibromatosis 1 and its variable expressivity make prenatal
      diagnosis appealing. We conducted our research to assess patient characteristics
      associated with the desire for prenatal diagnosis. Between 1995 and 2004, 361
      neurofibromatosis 1 adult patients were interviewed about their desire for
      prenatal diagnosis. Answers were classified in three groups: (1) 'no;' (2)
      'uncertain;' (3) 'yes.' Socio-demographical and clinical data were analyzed by
      logistic multinomial regression for their association with the desire for
      prenatal diagnosis. Male-to-female sex ratio was 0.93. Mean age at study +/- SD
      was 33.5 +/- 10. Seven four patients (20.5%) would consider prenatal diagnosis;
      240 (66.5%) did not; and 47 (13.0%) were uncertain. In multivariate analysis,
      compared to the 'no' group, a longer follow-up (OR = 1.25 [1.11-1.41]), a younger
      age at study time (OR = 1.25 [1.11-1.41]), not having child (OR = 2.46 [1.03
      5.97]) and a higher educational level (OR = 5.07 [1.05-24.47]) were independently
      associated with the 'yes' group. Compared to the 'no' group individuals who were
      in the 'uncertain' groups were younger (0.95 [0.90-0.99]), less often married
      (0.11 [0.01-0.89]) and had a longer follow-up (1.26 [1.09-1.46]). There is a
      significant demand for prenatal diagnosis among neurofibromatosis 1 French
      patients. This demand is associated with individuals who are younger, have no
      child, have a longer follow up, and higher level of education.

PMID- 18076114
TI  - Retention of African American women in cancer genetics research.
AB  - Although retention is a critical component of longitudinal cancer genetics
      research, limited empirical data are available on predictors of study retention
      among populations that are difficult to enroll. We evaluated predictors of
      retention in cancer genetics research among African American women at increased
      risk for having a BRCA1 and BRCA2 (BRCA1/2) mutation. Participants were African
      American women (n = 192) at increased risk for hereditary breast-ovarian cancer
      who were enrolled in a longitudinal genetic counseling research study. Retention
      was evaluated separately for the 1- and 6-month follow-ups and in terms of
      overall retention (e.g., completion of both telephone interviews). Seventy-three
      percent of women and 65% of women were retained at the 1- and 6-month follow-ups
      respectively; in terms of overall retention, 60% of women were retained in both
      follow-up telephone interviews. Predictors of retention at 1-month included being
      employed (OR = 2.47, 95% CI = 1.24, 4.93, P = 0.01) whereas predictors of overall
      retention included having a personal history of breast and/or ovarian cancer (OR
      = 2.06, 95% CI = 1.07, 3.95, P = 0.03) and having completed genetic counseling
      (OR = 2.63, 95% CI = 1.39, 4.98, P = 0.003). These data suggest that once
      enrolled in genetic counseling research, the majority of African American women
      will continue to participate, especially if concrete clinical services are
      provided.

PMID- 18076115
TI  - Comparison of the potential for developmental toxicity of prenatal exposure to
      two dietary chromium supplements, chromium picolinate and
      [Cr3O(O2CCH2CH3)(6(H2O)3]+, in mice.
AB  - BACKGROUND: Chromium(III) is generally thought to be an essential trace element
      that allows for proper glucose metabolism. However, chromium(III) picolinate,
      Cr(pic)3, a popular dietary supplement form of chromium, has been shown to be
      capable of generating hydroxyl radicals and oxidative DNA damage in rats. The
      cation [Cr3O(O2CCH2CH3)(6(H2O)3]+, Cr3, has been studied as an alternative
      supplemental source of chromium. It has been shown to increase insulin
      sensitivity and lower glycated hemoglobin levels in rats, making it attractive as
      a potential therapeutic treatment for gestational diabetes. To date, no studies
      have been published regarding the safety of Cr3 supplementation to a developing
      fetus. METHODS: From gestation days (GD) 6-17, mated CD-1 female mice were fed
      diets delivering either 25 mg Cr/kg/day as Cr(pic)(3), 3.3 or 26 mg Cr/kg/day as
      Cr3, or the diet only to determine if Cr3 could cause developmental toxicity.
      Dams were sacrificed on GD 17, and their litters were examined for adverse
      effects. RESULTS: No signs of maternal toxicity were observed. No decrease in
      fetal weight or significantly increased incidence of skeletal defects was
      observed in the Cr3 or Cr(pic)3 exposed fetuses compared to the controls.
      CONCLUSION: Maternal exposure to either Cr(pic)3 or Cr3 at the dosages employed
      did not appear to cause deleterious effects to the developing offspring in mice.

PMID- 18076116
TI  - The rapid estimate of adult literacy in genetics (REAL-G): a means to assess
      literacy deficits in the context of genetics.
AB  - Genetic information presents challenges to all patients, but particularly those
      with low and marginal literacy. The goal of the study was to create a rapid
      estimate of adult literacy in genetics (REAL-G) tool, with established validity,
      for use with patients receiving genetics services. Patterned after the widely
      used rapid estimate of adult literacy in medicine (REALM), a three-stage method
      was used in tool development. This included derivation of terms from transcripts
      of visits conducted by over 150 prenatal and cancer genetic counselors.
      Concurrent validity was estimated by administration of both the REAL-G and the
      REALM to 203 participants. Predictive validity was estimated by relating
      participants' REAL-G scores to scores on a learning task that involved viewing a
      videotaped genetic counseling session and answering related questions. The REAL-G
      measure was strongly correlated with the REALM (Pearson correlation = 0.83; P <
      0.0001), indicating substantial concurrent validity in a population of potential
      genetic counseling patients. Using the REALM as the gold standard, REAL-G scores
      identified readers at the sixth grade level or below (95.4% sensitivity and 88.5%
      specificity). Further analysis identified an eight-item subset of words that has
      strong concurrent validity when compared to longer instruments and even greater
      predictive power in relation to information recall. Subjects scoring below the
      sixth grade level on the eight-item REAL-G scored significantly lower than others
      on knowledge tests after viewing genetic counseling visits. The REAL-G represents
      a screening tool that can be used to quickly identify low literate patients in
      the clinical genetics context or to quantify context-specific literacy within a
      research setting.

PMID- 18076117
TI  - Characterization of interstitial Xp duplications in two families by tiling path
      array CGH.
AB  - Duplications of the short arm of the X chromosome in male patients are rare. We
      report on the clinical features of mentally retarded patients in two families
      with different interstitial duplications of Xp and their characterization by
      tiling path array comparative genomic hybridization (array CGH). In Family A, we
      detected a duplication of 9.3 Mb in Xp11p21 in a male with severe mental
      retardation [karyotype 46,XY,dup(X)(p11.3p21.1)] and his healthy mother. The
      clinical features of this patient--severe mental retardation, obesity,
      macrocephaly--are in accordance with those of a previously reported patient with
      a similar duplication. In Family B, a duplication of 8.5 Mb was diagnosed in Xp22
      in three male patients with mental retardation [karyotype
      46,XY,dup(X)(p22.11p22.2)] and two healthy females. Characterization of the
      duplications by array CGH enabled the identification of the genes within these
      intervals. These comprise known mental retardation genes such as MAOA, NDP,
      TM4SF2, NDP, RSK2, and CDKL5. Duplication of MAOA will be discussed as a possible
      cause of obesity.

PMID- 18076118
TI  - Mowat-Wilson syndrome with craniosynostosis: a case report.

PMID- 18076119
TI  - A patient with the syndrome of megalencephaly, mega corpus callosum and complete
      lack of motor development.
AB  - The syndrome of megalencephaly, mega corpus callosum and complete lack of motor
      development (MCC; OMIM 603387) is an apparently rare condition since only three
      sporadic cases have been reported [Gohlich-Ratmann et al. (1998); Am J Med Genet
      79:161-167]. We describe an additional case that was not diagnosed until age 15
      months. The MRI showed generalized, severe enlargement of the corpus callosum and
      thickening of the cortex. The cause for the MCC syndrome is unknown and both
      autosomal recessive and spontaneous dominant genetic mechanisms are
      possibilities.

PMID- 18076120
TI  - Single molecule polymerization, annealing and bundling dynamics of SipA induced
      actin filaments.
AB  - Salmonella bacteria cause more than three million deaths each year. They hijack
      cells and inject among other proteins SipA via a "molecular syringe" into the
      cell, which can tether actin subunits in opposing strands to form mechanically
      stabilized filaments which rapidly reshape the cells surface into extended
      ruffles, leading to bacterial internalization. Exactly how these ruffles form at
      a single filament level remains unknown. Our real time total internal
      fluorescence microscopy observations show that both bidirectional elongation of
      actin by SipA as well as end-to-end annealing of SipA-actin filaments are rapid
      processes. Complementary electron microscopy investigations demonstrate that
      crowding agents in vitro readily induce stiff bundles of SipA-actin filaments.
      Taken together these three effects, rapid SipA induced actin polymerization,
      filament annealing and bundle formation due to molecular crowding can explain how
      Salmonella invades cells at molecular level.

PMID- 18076121
TI  - Increased forensic efficiency of DNA fingerprints through simultaneous resolution
      of length and nucleotide variability by high-performance mass spectrometry.
AB  - Short tandem repeat (STR) typing is the most powerful method for determining the
      origin of a sample for a number of molecular disciplines such as medical
      genetics, population genetics, tumor analysis, transplantation medicine, or
      forensic crime scene analysis. STR alleles are routinely differentiated based
      upon their fragment size by electrophoresis under denaturing conditions, which
      does not take nucleotide variability into consideration. This simplification
      leads to loss of biological information as the nature of the individual sequence
      motifs that build an STR is not described. An alternative detection platform
      would be mass spectrometry, which captures the underlying sequence variation by
      comparing the molecular masses of DNA fragments. Here, we demonstrate that the
      combination of ion-pair reversed-phase high-performance liquid chromatography and
      electrospray ionization quadrupole time-of-flight mass spectrometry (ICEMS) is
      able to simultaneously detect length and nucleotide variability in STRs. Overall,
      21 forensically relevant STRs that are also used in other scientific fields were
      screened in an Austrian population sample for the occurrence of nucleotide
      variability within or close to the repeat region. A total of 11 of the
      investigated loci (SE33, D2S1338, vWA, D21S11, D3S1358, D16S539, D8S1179, D7S820,
      D13S317, D5S818, and D2S441) brought additional allele (sequence) variants.
      Forensic efficiency, as determined by typical statistical parameters, was
      significantly increased by 20 to 30%. The beauty of ICEMS-STR-analysis is the
      fact that it represents one of the few technological advancements that allows
      direct comparison of newly generated data with existing data such as stored in
      DNA databases, which have a retarding effect on new developments.

PMID- 18076122
TI  - Mutation analysis in nephronophthisis using a combined approach of homozygosity
      mapping, CEL I endonuclease cleavage, and direct sequencing.
AB  - Nephronophthisis (NPHP), an autosomal recessive kidney disease, is the most
      frequent genetic cause of chronic renal failure in the first three decades of
      life. Mutations in eight genes (NPHP1-8) have been identified. We here describe a
      combined approach for mutation screening of NPHP1, NPHP2, NPHP3, NPHP4, and NPHP5
      in a worldwide cohort of 470 unrelated patients with NPHP. First, homozygous
      NPHP1 deletions were detected in 97 patients (21%) by multiplex PCR. Second, 25
      patients with infantile NPHP were screened for mutations in inversin
      (NPHP2/INVS). We detected a novel compound heterozygous frameshift mutation
      (p.[Q485fs]+[R687fs]), and a homozygous nonsense mutation (p.R899X). Third, 37
      patients presenting with NPHP and retinitis pigmentosa (Senior-Loken syndrome
      [SLS]) were screened for NPHP5/IQCB1 mutations by direct sequencing. We
      discovered five different (three novel) homozygous premature termination codon
      (PTC) mutations (p.F142fsX; p.R461X; p.R489X; p.W444X; and c.488-1G>A). The
      remaining 366 patients were further investigated for mutations in NPHP1, NPHP3,
      and NPHP4. We applied a "homozygosity only" strategy and typed three highly
      polymorphic microsatellite markers at the respective loci. A total of 32, eight,
      and 14 patients showed homozygosity, and were screened by heteroduplex crude
      celery extract (CEL I) endonuclease digests. The sensitivity of CEL I was
      established as 92%, as it detected 73 out of 79 different known mutations simply
      on agarose gels. A total of 10 novel PTC mutations were found in NPHP1 (p.P186fs,
      p.R347X, p.V492fs, p.Y509X, and c.1884+1G>A), in NPHP3 (c.3812+2T>C and
      p.R1259X), and in NPHP4 (p.R59X, p.T1004fs, and p.V1091fs). The combined
      homozygosity mapping and CEL I endonuclease mutation analysis approach allowed us
      to identify rare mutations in a large cohort of patients at low cost.

PMID- 18076123
TI  - New case of interstitial deletion 12(q15-q21.2) in a girl with facial dysmorphism
      and mental retardation.
AB  - Interstitial deletions of the long arm of chromosome 12 are rare rearrangements
      with only 15 cases reported in the literature. The phenotype may include facial
      dysmorphism, developmental delay, ectodermal abnormalities, cardiac and renal
      malformations depending on breakpoints' position. Here, we describe a third case
      of 12(q15-q21.2) deletion ascertained through CGH-array analyses and provide a 5
      year follow-up. The patient presented with pre- and postnatal growth retardation,
      congenital heart defect, developmental delay, and facial dysmorphism changing
      with age, underlining the importance of long-term follow-up. We compared this new
      case with previous observations of 12q deletions in order to propose phenotype
      karyotype correlations.

PMID- 18076124
TI  - An efficient method for dephosphorylation of phosphopeptides by cerium oxide.
AB  - In this article, an effective method for dephosphorylation of phosphopeptides by
      cerium oxide is described. The dephosphorylation activity of cerium oxide was
      evaluated by two standard phosphopeptides and the phosphopeptides in digests of
      phosphoprotein alpha-casein and beta-casein. Results showed that the
      dephosphorylation of all the phosphopeptides was completed in 10 min, and
      temperature had little effect on the dephosphorylation, the dephosphorylation
      could be carried out at 0 degrees C, room temperature and 37 degrees C. The
      dephosphorylation mediated by cerium oxide can be attributed to Lewis acid and
      nucleophile activations. Advantages of using cerium oxide as catalyst for the
      dephosphorylation include: safe, simple, high catalytic activity, and no precise
      control of the treatment temperature. The method is valid for the phosphorylation
      of Ser, Thr and Tyr, and can be used for phosphoprotein analysis.

PMID- 18076125
TI  - Prediction of the effects of imperfect construction of a QMS filter.
AB  - Modelling techniques have previously predicted the observed behaviour of
      perfectly manufactured QMS mass filters. These methods are extended to
      examination of the behaviour of imperfect QMS filters; this examination considers
      the behaviour of QMS filters with one rod displaced radially inward as this is a
      simple manufacturing defect that arises when a rod does not fit correctly into
      the mounting. The results demonstrate the well known, but poorly documented
      property, that exchanging the connections of a poorly performing QMS device
      sometimes improves performance. This is shown to arise because only a
      displacement of a y-rod produces a large effect. The results also show that
      displacement of a y-rod may produce a spurious additional peak known as a
      precursor. More detailed investigation suggests that precursors are not separate
      peaks but are formed because a section of the main peak is removed causing an
      apparent double peak. Finally results confirm that adjustment of the voltage
      applied to a displaced rod can be used to significantly improve the QMS
      behaviour. A small change by a fraction alpha in the position of a single rod may
      be compensated by a change of 2 x alpha in the voltage applied to that rod.

PMID- 18076126
TI  - Functional and structural characterization of apidaecin and its N-terminal and C
      terminal fragments.
AB  - Two aspects were studied to elucidate the functional and structural
      characterization of apidaecin and its N-terminal and C-terminal fragments: (i)
      Functions of the N-terminal and C-terminal fragments of apidaecin were first
      studied by measuring their antibacterial activity, their ability to enter
      Escherichia coli cells and their effects on the activities of beta-galactosidase
      and alkaline phosphatase. The results indicate that neither the N-terminal nor
      the C-terminal of apidaecin contains intracellular delivery unit or active
      segment. (ii) The effect of apidaecin on the ATPase activity of DnaK, and the
      interactions of apidaecin with E.coli lidless DnaK and DnaK D-E helix were
      studied. Results showed that apidaecin could interact with the E.coli lidless
      DnaK protein and stimulate its ATPase activity, but not with E.coli DnaK D-E
      helix. This indicated that the antimicrobial activity of apidaecin may be shown
      by stimulating the ATPase activity of DnaK by binding to its conventional
      substrate-binding site, to decrease its cellular concentration of DnaK by
      competing with natural substrates and inhibit the enzymes' activities of E. coli
      cells. It is the first study to suggest that the apidaecin-binding site of DnaK
      is the conventional substrate binging site.

PMID- 18076127
TI  - Hospital discharge among frail elderly people: a pilot study in Sweden.
AB  - A conceptual framework for the hospital discharge process was designed. It was
      intended to measure frail elderly people's experience of their quality of care in
      terms of satisfaction and trustworthiness during their hospital discharge and
      their experience at home. The present pilot study aimed at evaluating the
      viability of an occupational therapy clinical tool. Nine frail elderly Swedish
      individuals reported the quality of their care as mostly satisfactory and
      trustworthy, according to their responses to the Discharged Patients' Enquiry
      Questionnaire (DPEQ). However, the participants were not satisfied with the non
      continuity among the home-helpers, the lack of rehabilitation services and the
      non-availability of professional help, for example occupational therapy for
      increasing social contacts. The participant's responses indicated that
      occupational therapy interventions, that is, assessment of home environment (n =
      6), improvement of housing accessibility (n = 3) and prescription of assistive
      devices (n = 4), contributed to their ability to live at home. The results are
      limited owing to the small number of participants. Future investigations of the
      care that patients discharged from hospitals receive are recommended to explore
      supplementary assessments of spouses' care burden and participants' quality of
      life, and the psychometric functions of the conceptual framework. In summary, the
      conceptual framework described may be a viable tool for evaluating the discharge
      process among frail elderly people discharged from hospitals to their homes.

PMID- 18076128
TI  - Protective vaccination with hepatitis C virus NS3 but not core antigen in a novel
      mouse challenge model.
AB  - BACKGROUND: Efficient vaccines against hepatitis C virus (HCV) infection are
      urgently needed. Vaccine development has been hampered by the lack of suitable
      small animal models to reliably test the protective capacity of immmunization.
      METHODS: We used recombinant murine gammaherpesvirus 68 (MHV-68) as a novel
      challenge virus in mice and tested the efficacy of heterologous candidate human
      vaccines based on modified vaccinia virus Ankara or adenovirus, both delivering
      HCV non-structural NS3 or core proteins. RESULTS: Recombinant MHV-68 expressing
      NS3 (MHV-68-NS3) or core (MHV-68-core) were constructed and characterized in
      vitro and in vivo. Mice immunized with NS3-specific vector vaccines and
      challenged with MHV-68-NS3 were infected but showed significantly reduced viral
      loads in the acute and latent phase of infection. NS3-specific CD8+ T cells were
      amplified in immunized mice after challenge with MHV-68-NS3. By contrast, we did
      neither detect a reduction of viral load nor an induction of core-specific CD8+ T
      cells after core-specific immunization. CONCLUSIONS: Our data suggest that the
      challenge system using recombinant MHV-68 is a highly suitable model to test the
      immunogenicity and protective capacity of HCV candidate vaccine antigens. Using
      this system, we demonstrated the usefulness of NS3-specific immunization. By
      contrast, our analysis rather discarded core as a vaccine antigen.

PMID- 18076129
TI  - Nonparametric inference on the E/O ratio in model validation.
AB  - In preventing diseases such as cancers and osteoporosis, statistical models are
      often used to identify subjects with high risks. The ratio of the expected (or
      predicted) number of cases in the target population and the observed numbers of
      cases (the E/O ratio) is a useful quantity to evaluate the goodness of fit of the
      model. The model is usually evaluated on a sample taken from the target
      population and, in the literature, statistical inferences on the E/O ratio often
      assume that the expected number is a constant and the observed number follows a
      Poisson distribution. In this paper, we introduce a nonparametric method that
      takes into account the variability of the predicted number due to sampling and
      its correlation with the observed number. By estimating the variance of the
      estimated E/O ratio more accurately, this nonparametric approach offers better
      inferences. In addition, we propose to use an F-statistic to test the goodness of
      a model across subgroups defined by certain risk factors.

PMID- 18076131
TI  - Exploring event-related brain dynamics with tests on complex valued time
      frequency representations.
AB  - A question subject to intense debate is whether scalp-recorded event-related
      brain potentials are due to phase resetting of the ongoing electroencephalogram
      (EEG) or rather to the superimposition of time-locked components on background
      activity. The two hypotheses are usually assessed by means of statistics in the
      time-frequency domain, for example, through wavelet transformation of multiple
      EEG trials that yield for each time and frequency a scatter plot of complex
      values coefficients. Currently, intertrial phase correlation (phase locking or
      phase coherence) is taken as evidence for phase resetting at a given frequency
      and latency. Here we present a formal analysis using a complex t-statistic to
      illustrate that such measures are, in effect, tests for the mean vector of the
      repeated trials, and as such on their own are inappropriate measures of phase
      resetting. We also propose simple t-like statistics for testing changes in (i)
      the mean (presence of an event-related potential), (ii) the amplitude variance
      (presence of (de)synchronization) and (iii) the concentration of phases (phase
      locking). The first two statistics are found to be proper measures of the
      presence of a non-zero mean activity and induced activity, respectively. In the
      third case, two different tests are introduced: one based on measuring the
      alignment of coefficients in the complex plane and another derived from the
      argument that phase locking persists when the mean of the coefficients is
      removed. Both statistics gave unambiguous evidence of the presence of phase
      locking suggesting that they constitute promising tools in the analysis of event
      related brain dynamics.

PMID- 18076130
TI  - Co-expression of MGMT(P140K) and alpha-L-iduronidase in primary hepatocytes from
      mucopolysaccharidosis type I mice enables efficient selection with metabolic
      correction.
AB  - BACKGROUND: Systemic in vivo gene therapy has resulted in widespread correction
      in animal models when treated at birth. However, limited improvement was observed
      in postnatally treated animals with mainly targeting to the liver and bone
      marrow. It has been shown that an O(6)-methylguanine-DNA-methyltransferase
      variant (MGMT(P140K)) mediated in vivo selection of transduced hematopoietic stem
      cells (HSC) in animals. METHODS: We investigated the feasibility of MGMT(P140K)
      mediated selection in primary hepatocytes from a mouse model of
      mucopolysaccharidosis type I (MPS I) in vitro using lentiviral vectors. RESULTS:
      We found that multiple cycles of O(6)-benzylguanine (BG)/1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU) treatment at a dosage effective for ex vivo HSC selection led
      to a two-fold increase of MGMT-expressing primary hepatocytes under culture
      conditions with minimum cell expansion. This enrichment level was comparable to
      that obtained after selection at a hepatic maximal tolerated dose of BCNU.
      Similar levels of increase were observed regardless of initial transduction
      frequency, or the position of MGMT (upstream or downstream of internal ribosome
      entry site) in the vector constructs. In addition, we found that elongation
      factor 1alpha promoter was superior to the long-terminal repeat promoter from
      spleen focus-forming virus with regard to transgene expression in primary
      hepatocytes. Moreover, the levels of therapeutic transgene expression in
      transduced, enzyme-deficient hepatocytes directly correlated with the doses of
      BCNU, leading to metabolic correction in transduced hepatocytes and metabolic
      cross-correction in neighbouring non-transduced MPS I cells. CONCLUSIONS: These
      results demonstrate that MGMT(P140K) expression confers successful
      protection/selection in primary hepatocytes, and provide 'proof of concept' to
      the prospect of MGMT(P140K)-mediated co-selection for hepatocytes and HSC using
      BG/BCNU treatment.

PMID- 18076132
TI  - Reconstituting retroviral (ReCon) vectors facilitating delivery of cytotoxic
      genes in cancer gene therapy approaches.
AB  - BACKGROUND: We have previously described the generation of reconstituting
      retroviral (ReCon) vectors designed for cancer gene therapy using cytotoxic gene
      products. The unique vector structure with a promoter physically separated from
      the transgene allows generation of stable virus producer cells irrespective of
      the toxic gene. The mechanism of synthesis of DNA from retroviral RNA dictates
      that infection leads to the reconstitution of functional expression cassettes in
      the target cell. METHODS: To improve vector titres, a cytomegalovirus enhancer
      was inserted upstream of the 5'-long-terminal repeat (LTR); the Woodchuck
      hepatitis virus post-transcriptional regulatory element and an elongated
      attachment site upstream of the 3'-LTR were included. In addition, a bacterial
      origin of replication was deleted and a functional internal polyadenylation
      signal mutated. Transcriptional targeting was attempted by introducing mammary
      tissue-specific promoters such as the U3 region of mouse mammary tumour virus or
      the promoter of the whey acidic protein encoding gene. All modifications were
      analysed in detail with respect to virus production and infectivity. Finally, the
      vector was armed with the lambda-holin encoding gene and transduced cells were
      analysed for cytotoxic effects. RESULTS: Distinct modifications of the vector
      resulted in a titre improvement of more than 560-fold. Compatibility of the
      optimized vector with targeted cellular promoters was demonstrated. When equipped
      with the cytotoxic gene, stable producer cells could be successfully established
      and high titre virus infection resulted in rigorous target cell killing.
      CONCLUSIONS: The ReCon vector in its optimized form is an attractive tool for
      cancer gene therapy approaches.

PMID- 18076133
TI  - Which aspects of cognitive function are best associated with testamentary
      capacity in patients with Alzheimer's disease?

PMID- 18076134
TI  - Kinetic and mechanistic studies of the electrocatalytic reduction of O2 TO H2O
      with mononuclear Cu complexes of substituted 1,10-phenanthrolines.
AB  - Mononuclear Cu complexes with a 1,10-phenanthroline-based ligand adsorbed onto an
      edge-plane graphite electrode act as electrocatalysts for the 4-electron
      reduction of O2 to H2O. A mechanism is proposed for the electrocatalytic O2
      reduction that accounts for the observed redox and kinetic dependences on
      coordinating anions and proton donors in the buffer. Systematic increases of
      ligand electron-withdrawing properties and/or the steric demands near the Cu
      center increase the E0 of the Cu catalysts but decrease the rate of O2 reduction.
      The kinetic rate of O2 reduction at E0, reported as kinetic current divided by
      catalyst redox charge, decreases as E0 increases: from 16 s(-1) measured at E0 in
      air-saturated solutions for adsorbed Cu(phen) to 0.4 s(-1) for Cu(2,9-Et2-phen).
      The maximum value of E for which catalytic activity can be attained is estimated
      to be +350 mV vs NHE. Near E0, the kinetic current deviates from that expected if
      O2 binding were the sole rate-limiting step. This indicates that one or more of
      the electrochemical reduction steps are rate limiting at potentials near E0.

PMID- 18076135
TI  - Local and nonlocal environments around Cis peptides.
AB  - Although the vast majority of peptide bonds in folded proteins are found in the
      trans conformation, a small percentage are found in the less energetically
      favorable cis conformation. Though the mechanism of cis peptide bond formation
      remains unknown, the role of local aromatics has been emphasized in the
      literature. This paper presents results from a comprehensive statistical analysis
      of both the local and nonlocal (i.e., tertiary) environment around cis peptides.
      In addition to an increased frequency of aromatic residues in the local
      environment around cis peptides, a number of nonlocal differences in protein
      secondary and tertiary structure between cis and trans peptides are found: (i)
      coil regions containing cis peptides are almost twice as long as those without
      cis peptides and include more Tyr and Pro residues; (ii) cis peptides occur with
      high frequencies in coil regions near large beta-structures; (iii) there is a
      nonlocal enrichment of Cys, His, Tyr, and Ser in the tertiary environment
      surrounding cis peptides when compared to trans peptides; and (iv) on average,
      cis peptides make fewer medium-range and more long-range contacts than trans
      peptides do. On the basis of these observations, it is concluded that nonlocal
      factors play a significant role in cis peptide formation, which has not been
      fully appreciated previously. An autocatalytic model for cis peptide formation is
      discussed as are consequences for protein folding.

PMID- 18076136
TI  - A proteome resource of ovarian cancer ascites: integrated proteomic and
      bioinformatic analyses to identify putative biomarkers.
AB  - Epithelial ovarian cancer is the most lethal gynecological malignancy, and
      disease-specific biomarkers are urgently needed to improve diagnosis, prognosis,
      and to predict and monitor treatment efficiency. We present an in-depth proteomic
      analysis of selected biochemical fractions of human ovarian cancer ascites,
      resulting in the stringent and confident identification of over 2500 proteins.
      Rigorous filter schemes were applied to objectively minimize the number of false
      positive identifications, and we only report proteins with substantial peptide
      evidence. Integrated computational analysis of the ascites proteome combined with
      several recently published proteomic data sets of human plasma, urine, 59 ovarian
      cancer related microarray data sets, and protein-protein interactions from the
      Interologous Interaction Database I (2)D ( http://ophid.utoronto.ca/i2d) resulted
      in a short-list of 80 putative biomarkers. The presented proteomics analysis
      provides a significant resource for ovarian cancer research, and a framework for
      biomarker discovery.

PMID- 18076137
TI  - A comparative study on computational two-block motif detection: algorithms and
      applications.
AB  - Since the completion of human genome sequencing, cataloging of all genomic
      functional elements has been one of the challenging problems in bioinformatics.
      Deciphering cis-regulatory elements in the human genome still remains elusive
      although much effort has been expended. This paper reviews a suite of methods for
      two-block motif discovery including mathematical modeling, de novo motif-finding
      based on multiple local alignment, and genomic sequence scanning method for
      putative sites. We formulate a general method to address this challenge and
      compare two major existing algorithms (i.e., greedy local search and Gibbs
      sampling) implemented to solve the popular two-block structured motif discovery
      issue. We demonstrate how to use this suite of methods and apply them to human
      nuclear receptor response elements (i.e., protein binding sites of several
      relevant nuclear receptors, HNF4alpha, CAR/RXR, and PXR/RXR).

PMID- 18076138
TI  - Synthesis and characterization of four-arm poly(ethylene glycol)-based gene
      delivery vehicles coupled to integrin and DNA-binding peptides.
AB  - The goal of this study was to develop a gene delivery vehicle that can
      specifically target cell surface receptors with low nonspecific protein
      adsorption and low cytotoxicity. Toward this goal, four-arm poly(ethylene glycol)
      vehicles were functionalized with DNA-binding peptides (DBPs) and integrin
      binding (RGD) peptides. We have previously described a novel PEG-based gene
      delivery vehicle functionalized with DBPs that successfully transfected Chinese
      hamster ovary (CHO) cells with low toxicity and low protein adsorption. This work
      investigated whether incorporating RGD peptides onto PEG-DBP vehicles could
      target specific cell surface receptors and increase transfection efficiency of
      HEPG2 cells. DBP and RGD peptides were coupled onto PEG-tetraacrylate (PEG-TA) in
      three combinations (molar ratios of DBP:RGD of 1:3, 2:2, and 3:1) and
      characterized by measuring particle size, zeta potential, and transfection
      efficiency as a function of charge ratio (peptide amine groups:DNA phosphate).
      Nonspecific protein adsorption and cytotoxicity of PEG-DBP-RGD vehicles were also
      measured. Dynamic light scattering showed that PEG-DBP-RGD vehicles condensed DNA
      into particles having mean diameters of 250-300 nm and zeta potentials ranging
      from -10 to 7 mV. It was found that coupling two RGD peptides to the PEG-DBP 2
      vehicle increased the transfection efficiency at a polymer/DNA charge ratio of
      5:1 (+/-) and 6:1 (+/-) and that these vehicles had transfection efficiencies
      similar to those of polyethylenimine (PEI)/DNA particles. However, coupling one
      or three RGD peptides to PEG-DBP vehicles did not increase the transfection
      efficiency. Additionally, the PEG-DBP-RGD/DNA particles adsorbed less protein
      than PEI particles and were less toxic to HEPG2 cells.

PMID- 18076139
TI  - A real-time QCM-D approach to monitoring mammalian DNA damage using DNA adsorbed
      to a polyelectrolyte surface.
AB  - We have successfully demonstrated that the quartz crystal microbalance with
      dissipation monitoring (QCM-D) can be used to monitor real-time damage to genomic
      mammalian DNA adsorbed to a polyelectrolyte surface. To reveal the capabilities
      of this technique, we exposed DNA surfaces to quercetin, an agent that has been
      implicated in causing DNA strand breaks in a Cu(II)-dependent fashion in vitro.
      We show that the QCM-D frequency and dissipation patterns that result from
      exposure of the DNA surfaces to quercetin-Cu(II) are consistent with the
      induction of DNA strand scission. We use QCM-D to furthermore demonstrate that
      this process is dependent on Cu(II) and that the DNA damage induced by quercetin
      can still be detected if Cu(II) is in situ with the DNA surface and not in
      solution phase.

PMID- 18076140
TI  - Curcumin induces high levels of topoisomerase I- and II-DNA complexes in K562
      leukemia cells.
AB  - Recent data suggest that curcumin, a phytochemical with cancer chemopreventive
      potential, might be useful in the treatment of several solid and hematological
      malignancies. DNA topoisomerases (topos) are the target of several drugs commonly
      used in cancer chemotherapy. These drugs induce topo-DNA complexes with either
      topo I or topo II; then cellular processing converts these complexes into
      permanent DNA strand breaks that trigger cell death. Using the TARDIS in vivo
      assay, this study shows for the first time that curcumin induces topo I and topo
      II (alpha and beta)-DNA complexes in K562 leukemia cells. A comparative analysis
      revealed that the levels of these complexes were higher than those induced by
      several standard topo I and topo II inhibitors at equitoxic doses. Curcumin
      induced topo I and topo II-DNA complexes were prevented by the antioxidant N
      acetylcysteine; this suggests that, unlike the standard topo inhibitors, reactive
      oxygen species may mediate the formation of these complexes. Overall, this work
      shows that curcumin is capable of inducing topo-DNA complexes in cells with both
      topo I and topo II and increases the evidence suggesting that this dietary agent
      has potential to be tested in cancer chemotherapy.

PMID- 18076141
TI  - Diterpenes, sesquiterpenes, and a C15-acetogenin from the marine red alga
      Laurencia mariannensis.
AB  - In addition to 10 known compounds (7- 16), one new brominated diterpene, 10
      hydroxykahukuene B (1), two new sesquiterpenes, 9-deoxyelatol (2) and
      isodactyloxene A (3), one new brominated C 15-acetogenin, laurenmariallene (4),
      and two new naturally occurring halogenated sesquiterpenes (5 and 6) that were
      previously obtained as intermediates in a biomimetic synthetic study of
      rhodolaureol and rhodolauradiol have been isolated and identified from the
      organic extract of the marine red alga Laurencia mariannensis. The structures of
      these compounds were established by spectroscopic methods. The antibacterial and
      antifungal activities of new compounds 1-4 were evaluated.

PMID- 18076142
TI  - Anthraquinones with quinone reductase-inducing activity and benzophenones from
      Morinda citrifolia (noni) roots.
AB  - Two new benzophenones, morintrifolins A ( 1) and B ( 2), together with 14 known
      anthraquinones and four other known compounds, were isolated from a chloroform
      soluble extract of Morinda citrifolia roots. Of the isolated compounds, four
      known anthraquinones, namely, 1,2-dihydroxyanthraquinone ( 3), 1,3-dihydroxy-2
      methylanthraquinone ( 4), 2-hydroxy-3-(hydroxymethyl)anthraquinone ( 5), and
      1,3,6-trihydroxy-2-methylanthraquinone ( 6), exhibited quinone reductase (QR)-
      inducing activity in Hepa lclc7 cells, with concentrations required to double QR
      activity of 12.0, 8.1, 0.94, and 0.56 microM, respectively.

PMID- 18076144
TI  - Synthesis of substituted alkoxy benzene minilibraries, for the discovery of new
      insect olfaction or gustation inhibitors.
AB  - We describe methods for the rapid generation of minilibraries of substituted
      alkoxy benzenes (consisting of 4-5 compounds), for screening as insect olfaction
      or gustation inhibitors. Synthetic or commercially available monoalkoxy benzene
      compounds were mixed and reacted with various alkyl halides to afford a first set
      of minilibraries. A second and third set were generated from allyloxy
      minilibraries via the Claisen rearrangement and subsequent alkylation of the
      ortho-allyl phenols. We have chosen to prepare a collection of small libraries
      (as opposed to one large library) to test the response insects exhibit toward
      blends of compounds. We demonstrate how our minilibraries can be screened, both
      against insect antennae and against expressed pheromone-binding proteins from the
      gypsy moth, Lymantria dispar.

PMID- 18076145
TI  - Effect of first-dimension undersampling on effective peak capacity in
      comprehensive two-dimensional separations.
AB  - The objective of this work is to establish a means of correcting the theoretical
      maximum peak capacity of comprehensive two-dimensional (2D) separations to
      account for the deleterious effect of undersampling first-dimension peaks.
      Simulations of comprehensive 2D separations of hundreds of randomly distributed
      sample constituents were carried out, and 2D statistical overlap theory was used
      to calculate an effective first-dimension peak width based on the number of
      observed peaks in the simulated separations. The distinguishing feature of this
      work is the determination of the effective first-dimension peak width using the
      number of observed peaks in the entire 2D separation as the defining metric of
      performance. We find that the ratio of the average effective first-dimension peak
      width after sampling to its width prior to sampling (defined as <beta>) is a
      simple function of the ratio of the first-dimension sampling time (t(s)) to the
      first-dimension peak standard deviation prior to sampling (1sigma): <beta> =
      square root1+0.21(t /(s)(1) sigma(2) This is valid for 2D separations of
      constituents having either randomly distributed or weakly correlated retention
      times, over the range of 0.2 </= t(s)/1 sigma < or = 16. The dependence of <beta>
      on t(s)/1 sigma from this expression is in qualitative agreement with previous
      work based on the effect of undersampling on the effective width of a single
      first-dimension peak, but predicts up to 35% more broadening of first-dimension
      peaks than is predicted by previous models. This simple expression and accurate
      estimation of the effect of undersampling first-dimension peaks should be very
      useful in making realistic corrections to theoretical 2D peak capacities, and in
      guiding the optimization of 2D separations.

PMID- 18076146
TI  - Loss of the calmodulin-dependent inhibition of the RyR1 calcium release channel
      upon oxidation of methionines in calmodulin.
AB  - The oxidation of methionines in calmodulin (CaM) can affect the activity of
      calcium pumps and channels to modulate the amplitude and duration of calcium
      signals. We have therefore investigated the possible oxidation of CaM in skeletal
      muscle and its effect on the CaM-dependent regulation of the RyR1 calcium release
      channel. Taking advantage of characteristic reductions in electrophoretic
      mobility determined by SDS-PAGE, we find that approximately two methionines are
      oxidized in CaM from skeletal muscle. The functional effect of CaM oxidation on
      the open probability of the RyR1 calcium release channel was assessed through
      measurements of [3H]ryanodine binding using a heavy sarcoplasmic reticulum
      preparation enriched in RyR1. There is a biphasic regulation of RyR1 by
      unoxidized CaM, in which calcium-activated CaM acts to enhance the calcium
      sensitivity of channel closure, while apo-CaM functions to enhance channel
      activity at resting calcium levels. We find that physiological levels of CaM
      oxidation preferentially weaken the CaM-dependent inhibition of the RyR1 calcium
      release channel observed at activating micromolar levels of calcium. In contrast,
      the oxidation of CaM resulted in minimal functional changes in the CaM-dependent
      activation of RyR1 at resting nanomolar calcium levels. Oxidation does not
      significantly affect the high-affinity binding of calcium-activated CaM to the
      CaM-binding sequence of RyR1; rather, methionine oxidation disrupts interdomain
      interactions between the opposing domains of CaM in complex with the CaM-binding
      sequence of RyR1 that normally function as part of a conformational switch
      associated with RyR1 inhibition. These results suggest that the oxidation of CaM
      can contribute to observed elevations in intracellular calcium levels in response
      to conditions of oxidative stress observed during biological aging. We suggest
      that the sensitivity of RyR1 channel activity to CaM oxidation may function as
      part of an adaptive cellular response that enhances the duration of calcium
      transients to promote enhanced contractility.

PMID- 18076143
TI  - The search for endogenous activators of the aryl hydrocarbon receptor.
AB  - The primary design of this perspective is to describe the major ligand classes of
      the aryl hydrocarbon receptor (AHR). A grander objective is to provide models
      that may help define the physiological activator or "endogenous ligand" of the
      AHR. We present evidence supporting a developmental role for the AHR and propose
      mechanisms by which an endogenous ligand and consequent AHR activation might be
      important during normal physiology and development. From this vista, we survey
      the known xenobiotic, endogenous, dietary, and "unconventional" activators of the
      AHR, including, when possible, information about their induction potency,
      receptor binding affinity, and potential for exposure. In light of the essential
      function of the AHR in embryonic development, we discuss the candidacy of each of
      these compounds as physiologically important activators.

PMID- 18076147
TI  - Structures and micelle locations of the nonlipidated and lipidated C-terminal
      membrane anchor of 2',3'-cyclic nucleotide-3'-phosphodiesterase.
AB  - 2,3'-Cyclic nucleotide-3'-phosphodiesterase (CNP) is a myelin-associated protein,
      an enzyme abundantly present in the central nervous system of mammals and some
      vertebrates. In vitro, CNP specifically catalyzes the hydrolysis of 2',3'-cyclic
      nucleotides to produce 2'-nucleotides, but the physiologically relevant in vivo
      substrate is still unknown. Recently, it was found that CNP is a possible linker
      protein between microtubules and the plasma membranes. Since CNP is modified post
      translationally by an isoprenylation process at its C terminus, the prenylation
      is hypothesized to be a requisite process, which permanently anchors CNP to the
      plasma membrane. This study investigates the molecular mechanism of the
      interaction between CNP and the plasma membrane, proposing a general model to
      interpret the structural bases of prenylated proteins binding to the membrane. A
      13 residue, C-terminal CNP fragment, C13, was demonstrated to be directly
      responsible for CNP membrane anchoring. C13 and its lipidated derivative (LIPO
      C13) were subjected to conformational analysis in membrane mimetic environments,
      by means of CD and NMR spectroscopies. The orientation of C13 in relation to the
      membrane was investigated by NMR and EPR spin labeling studies. Our structural
      investigation shows that the presence of the lipidic tail is essential for the
      peptide to be folded and correctly positioned on the membrane surface. A general
      model is proposed in which the post-translational lipidation is an important
      biomolecular trick to enlarge the hydrophobic surface and to enable the contact
      of the protein with membrane.

PMID- 18076148
TI  - Proton affinity of methyl peroxynitrate.
AB  - The equilibrium structures, harmonic vibrational frequencies of methyl
      peroxynitrate, and structures of protonated methyl peroxynitrate have been
      investigated using ab initio methods. The methods include the single- and double
      excitation quadratic configuration (QCISD) methods and the QCISD(T) method, which
      incorporates a perturbational estimate of the effects of corrected triple
      excitation. The lowest-energy gas-phase form of protonated methyl peroxynitrate
      is a complex between CH3OOH and NO2+. The CH3OOH.NO2+ complex is bound by 22 +/-
      2 kcal/mol. The estimated proton affinity of methyl peroxynitrate is 178.8 +/- 3
      kcal/mol. A general trend for the proton affinity of ROO-NO2 (peroxynitrates)
      compounds is discussed.

PMID- 18076149
TI  - Characterizing the properties of the N7,N9-dimethylguaninium chloride ion pairs:
      prospecting for the design of a novel ionic liquid.
AB  - The structures, infrared spectra, and electronic properties of the N7,N9
      dimethylguaninium chloride have been studied. The interaction of one cation with
      one to four Cl anions and one Cl anion with two cations were investigated.
      Fifteen stable conformers are obtained. It is found that there are four acidic
      regions in the vicinity of the guaninium cations. In these regions, the cation
      could H-bond with one to three Cl anions but no more than three nearest anions.
      One Cl anion could H-bond with two cations. Additionally, evidence of a Cl...pi
      interaction between the anion and cation is observed. Among these structures, one
      cation interaction with two anions and two cations interaction with one anion
      have the larger interaction energies than the other series. Natural bond orbital
      analyses and molecular orbitals reveal that the charge transfer from anion(s) to
      the cation(s) occurs mainly through either the Cllp --> sigma C-H, Cllp --> sigma
      N-H, or Cllp --> pi C8-N7 interactions. The interaction between Cl and sigma (C/N
      H) or pi C-N produces a small bond order. This indicates that the Cl...H
      (Cl...pi) interaction exhibits a weak covalent character and suggests a strong
      ionic H-bond (Cl...pi bond). What's more, formation of Cl...H/Cl...pi bond
      decreases the bond order of the associated C/N-H bond or C8-N7 bond. In addition,
      examination of vibrational spectrum of each conformer explains the origin of H
      bonding character.

PMID- 18076150
TI  - Two-dimensional H2O-Cl2 and H2O-Br2 potential surfaces: an ab initio study of
      ground and valence excited electronic states.
AB  - All electron ab initio calculations for the interaction of H2O with Cl2 and Br2
      are reported for the ground state and the lowest triplet and singlet Pi excited
      states as a function of both the X-X and O-X bond lengths (X = Cl or Br). For the
      ground state and lowest triplet state, the calculations are performed with the
      coupled cluster singles, doubles, and perturbative triple excitation level of
      correlation using an augmented triple-zeta basis set. For the 1Pi state the
      multireference average quadratic coupled cluster technique was employed. For
      several points on the potential, the calculations were repeated with the
      augmented quadruple-zeta basis set. The ground-state well depths were found to be
      917 and 1,183 cm-1 for Cl2 and Br2, respectively, with the triple-zeta basis set,
      and they increased to 982 and 1,273 cm-1 for the quadruple-zeta basis set. At the
      geometry of the ground-state minimum, the lowest energy state corresponding to
      the unperturbed 1Pi states of the halogens increases in energy by 637 and 733 cm
      1, respectively, relative to the ground-state dissociation limit of the H2O-X2
      complex. Adding the attractive ground-state interaction energy to that of the
      repulsive excited state predicts a blue-shift, relative to that of the free
      halogen molecules, of approximately 1,600 cm-1 for H2O-Cl2 and approximately
      2,000 cm-1 for H2O-Br2. These vertical blue-shifts for the dimers are greater
      than the shift of the band maximum upon solvation of either halogen in liquid
      water.

PMID- 18076151
TI  - Absolute proton affinity for acetaldehyde.
AB  - Dissociative photoionization mass spectrometry has been used to measure
      appearance energies for the 1-hydroxyethyl cation (CH(3)CH=OH(+)) formed from
      ethanol and 2-propanol. Molecular orbital calculations for these two unimolecular
      fragmentation reactions suggest that only methyl loss from ionized 2-propanol
      does not involve excess energy at the threshold. The experimental appearance
      energy of 10.31 +/- 0.01 eV for this latter process results in a 298 K heat of
      formation of 593.1 +/- 1.2 kJ mol(-1) for CH(3)CH=OH(+) and a corresponding
      absolute proton affinity for acetaldehyde of 770.9 +/- 1.3 kJ mol(-1). This value
      is supported by both high-level ab initio calculations and a proposed upward
      revision of the absolute isobutene proton affinity to 803.3 +/- 0.9 kJ mol(-1). A
      298 K heat of formation of 52.2 +/- 1.9 kJ mol(-1) is derived for the tert-butyl
      radical.

PMID- 18076152
TI  - 3D QSAR and molecular docking studies of benzimidazole derivatives as hepatitis C
      virus NS5B polymerase inhibitors.
AB  - The urgent need for novel HCV antiviral agents has provided an impetus for
      understanding the structural requisites of NS5B polymerase inhibitors at the
      molecular level. Toward this objective, comparative molecular field analysis
      (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of 67 HCV
      NS5B polymerase inhibitors were performed using two methods. First, ligand-based
      3D QSAR studies were performed based on the lowest energy conformations employing
      the atom fit alignment method. Second, receptor-based 3D QSAR models were derived
      from the predicted binding conformations obtained by docking all NS5B inhibitors
      at the allosteric binding site of NS5B (PDB ID: 2dxs). Results generated from the
      ligand-based model were found superior (r2cv values of 0.630 for CoMFA and 0.668
      for CoMSIA) to those obtained by the receptor-based model (r2cv values of 0.536
      and 0.561 for CoMFA and CoMSIA, respectively). The predictive ability of the
      models was validated using a structurally diversified test set of 22 compounds
      that had not been included in a preliminary training set of 45 compounds. The
      predictive r2 values for the ligand-based CoMFA and CoMSIA models were 0.734 and
      0.800, respectively, while the corresponding predictive r2 values for the
      receptor-based CoMFA and CoMSIA models were 0.538 and 0.639, respectively. The
      greater potency of the tryptophan derivatives over that of the tyrosine
      derivatives was interpreted based on CoMFA steric and electrostatic contour maps.
      The CoMSIA results revealed that for a NS5B inhibitor to have appreciable
      inhibitory activity it requires hydrogen bond donor and acceptor groups at the 5
      position of the indole ring and an R substituent at the chiral carbon,
      respectively. Interpretation of the CoMFA and CoMSIA contour maps in context of
      the topology of the allosteric binding site of NS5B provided insight into NS5B
      inhibitor interactions. Taken together, the present 3D QSAR models were found to
      accurately predict the HCV NS5B polymerase inhibitory activity of structurally
      diverse test set compounds and to yield reliable clues for further optimization
      of the benzimidazole derivatives in the data set.

PMID- 18076153
TI  - Probing the complete folding trajectory of a DNA hairpin using dual beam
      fluorescence fluctuation spectroscopy.
AB  - The conformational fluctuations of dye-quencher labeled DNA hairpin molecules in
      aqueous solution were investigated using dual probe beam fluorescence fluctuation
      spectroscopy. The measurements revealed the flow and diffusion times of the DNA
      molecules through two spatially offset optical probe regions, the absolute and
      relative concentrations of each conformational substate of the DNA, and the
      kinetics of the DNA hairpin folding and unfolding reactions in the 1 micros to 10
      ms time range. A DNA hairpin containing a 21-nucleotide polythymine loop and a 4
      base pair stem exhibited double exponential relaxation kinetics, with time
      constants of 84 and 393 micros. This confirms that folding and melting of the DNA
      hairpin structure is not a two state process but proceeds by way of metastable
      intermediate states. The fast time constant corresponds to formation and
      unfolding of an intermediate, and the slow time constant is due to formation and
      disruption of the fully base-paired stem. This is consistent with a previous
      study of a similar DNA hairpin with a 5-base pair stem, in which the fast
      reaction was attributed to the fluctuations of an intermediate DNA conformation
      [J. Am. Chem. Soc. 2006, 128, 1240-1249]. In that case, reactions involving the
      native conformation could not be observed directly due to the limited observation
      time range of the fluorescence correlation spectroscopy experiment. The
      intermediate states of the DNA hairpins are suggested to be due to a collapsed
      ensemble of folded hairpins containing various partially folded or misfolded
      conformations.

PMID- 18076154
TI  - Magnetic field control of electron tunneling pathways in the monolayer of
      (ferrocenylmethyl)dodecyldimethylammonium bromide on a gold electrode.
AB  - The electron-tunneling reaction in the monolayer of
      (ferrocenylmethyl)dodecyldimethylammonium bromide (FDDA) and the mixed monolayer
      of FDDA and 11-mercaptoundecanoic acid (MUA) on gold electrodes was affected by
      homogeneous, steady magnetic fields perpendicular to the monolayer membrane. Both
      the current and peak-to-peak separation potential of the ferrocenyl/ferricenium
      redox couple in cyclic voltammograms increased with increasing magnetic field
      intensity. The electron tunneling reaction of FDDA depended not on the barrier
      thickness of the monolayer but on the electron tunneling pathways. The increase
      in the tilt angle of hydrocarbon chains of FDDA and MUA due to cooperative
      magnetic orientation may bring about change of the electron tunneling pathway of
      the through-bond to through-space. With increasing magnetic fields, the increase
      in the path length and interchain superexchange hops led to an increase in the
      peak-to-peak separation potential and tunneling current. The positive shift of
      the formal potential due to magnetic fields is ascribed to promotion of hydration
      around the redox couple.

PMID- 18076155
TI  - Sequence distribution effects on glass transition temperatures of copolymers: an
      extended Gibbs-DiMarzio equation in view of bond rotation flexibility.
AB  - In view of bond rotation flexibility and the additivity of stiff energy, a new
      equation containing mole fractions of sequences and glass transition temperatures
      (Tg's) of periodic copolymers was proposed. Meanwhile, the effect of
      stereochemical sequences was also taken into account. Even for the case of all
      substitutions on primary (C1), second (C2), and third (C3) carbon atoms adjoining
      to the given bond (triad sequences effect) to be considered, no intractable
      parameters exist in the new equation if the periodic copolymers of poly[AB],
      poly[AAB], and poly[BBA] could be acquired. This may facilitate its convenient
      application in comparison with the Ham equation (Ham, G. E. J. Macromol. Sci.
      Chem. 1975, A9, 461), which also concerned triad contributions. The new equation
      was applied to methyl methacrylate-styrene, ethylene-methyl methacrylate, and
      ethylene-vinyl acetate copolymers, and excellent fittings were obtained. The
      parameters obtained may predict Tg values of periodic copolymers that have not
      been acquired as well as provide useful information on the bond rotation
      flexibility.

PMID- 18076156
TI  - Synthesis and structural and magnetic characterization of cobalt(II) phosphonate
      cage compounds.
AB  - Reaction of cobalt salts with phosphonic acids in the presence of 6-chloro-2
      hydroxypyridine as a co-ligand, normally in its deprotonated form, leads to a
      series of new polymetallic cobalt cages. The most common structural type is a
      {Co(14)} cage which resembles a fragment of cobalt hydroxide. Variation of the
      phosphonate present and the cobalt salt leads to {Co(6)}, {Co(8)}, {Co(10)},
      {Co(11)}, {Co(12)}, {Co(13)}, and {Co(20)} cages, all of which have been
      characterized by X-ray crystallography. Magnetic studies of these cages show a
      general decline in the product chi(m)T with T, but for {Co(6)}, {Co(8)}, and
      {Co(12)} there are maxima at low temperature, which suggests nondiamagnetic
      ground states. Investigation of the dynamic behavior of the magnetization of
      these complexes shows that the octanuclear cage displays slow relaxation of
      magnetization.

PMID- 18076157
TI  - Preparation and characterization of dendrimer-templated Ag-Cu bimetallic
      nanoclusters.
AB  - Ag-Cu bimetallic nanoclusters with different shapes were prepared by a co
      complexation method in the presence of PAMAM dendrimers. Small and evenly sized
      spherical Ag-Cu bimetallic nanoparticles were obtained with N2H4.H2O as the
      reducing agent, and long rod-shaped bimetallic nanoclusters were prepared with
      NaBH4 as the reducing agent. The mechanisms of formation of Ag-Cu bimetallic
      nanolusters with different shapes were discussed. The different shapes of the
      cluster were likely caused by the differences in the reduction rate of metal ions
      with NaBH4 and N2H4.H2O. Structure characterization by TEM, UV-vis spectra, EDX,
      and TGA showed that, in the presence of PAMAM dendrimers, Ag-Cu alloy bimetallic
      nanorods were obtained with NaBH4 reduction, and Ag-Cu bimetallic nanoparticles
      were prepared with N2H4.H2O as the reducing agent.

PMID- 18076158
TI  - Coordination "oligomers" in self-assembly reactions of some "tritopic" picolinic
      dihydrazone ligands-mononuclear, dinuclear, hexanuclear, heptanuclear, and
      nonanuclear examples.
AB  - "Tritopic" picolinic dihydrazone ligands with tridentate coordination pockets are
      designed to produce homoleptic [3 x 3] nonanuclear square grid complexes on
      reaction with transition-metal salts, and many structurally documented examples
      have been obtained with Mn(II), Cu(II), and Zn(II) ions. However, other
      oligomeric complexes with smaller nuclearities have also been discovered and
      identified structurally in some reactions involving Fe(II), Co(II), Ni(II), and
      Cu(II), with certain tritopic ligands. This illustrates the dynamic nature of the
      metal-ligand interaction and the conformationally flexible nature of the ligands
      and points to the possible involvement of some of these species as intermediates
      in the [3 x 3] grid formation process. Examples of mononuclear, dinuclear,
      hexanuclear, heptanuclear, and nonanuclear species involving Fe(II), Co(II),
      Ni(II), and Cu(II) salts with a series of potentially heptadentate picolinic
      dihydrazone ligands with pyrazine, pyrimidine, and pyridine end groups are
      described in the present study. Iron and cobalt complexation reactions are
      complicated by redox processes, which lead to mixed-oxidation-state
      Co(II)/Co(III) systems when starting with Co(II) salts, and reduction of Fe(III)
      to Fe(II) when starting with Fe(III). Magnetic exchange within the polynuclear
      structural frameworks is discussed and related to the structural features.

PMID- 18076159
TI  - Study of neutral Fe(III) complexes of pyridoxal-N-substituted thiosemicarbazone
      with desolvation-induced spin-state transformation above room temperature.
AB  - The preparation and characterization of two new neutral ferric complexes with
      desolvation-induced discontinuous spin-state transformation above room
      temperature are reported. The compounds, [Fe(Hthpy)(thpy)].CH3OH.3H2O (1) and
      [Fe(Hmthpy)(mthpy)].2H2O (2), are low-spin (LS) at room temperature and below,
      whereas their nonsolvated forms are high-spin (HS), exhibiting zero-field
      splitting. In these complexes, Hthpy, Hmthpy, and thpy, mthpy are the
      deprotonated forms of pyridoxal thiosemicarbazone and pyridoxal
      methylthiosemicarbazone, respectively; each is an O,N,S-tridentate ligand. The
      molecular structures have been determined at 100(1) K using single-crystal X-ray
      diffraction techniques and resulted in a triclinic system (space group P1) and
      monoclinic unit cell (space group P21/c) for 1 and 2, respectively. Structures
      were refined to the final error indices, where RF = 0.0560 for 1 and RF = 0.0522
      for 2. The chemical inequivalence of the ligands was clearly established, for the
      "extra" hydrogen atom on the monodeprotonated ligands (Hthpy, Hmthpy) was found
      to be bound to the nitrogen of the pyridine ring. The ligands are all of the
      thiol form; the doubly deprotonated chelates (thpy, mthpy) have C-S bond lengths
      slightly longer than those of the singly deprotonated forms. There is a three
      dimensional network of hydrogen bonds in both compounds. The discontinuous spin
      state transformation is accompanied with liberation of solvate molecules. This is
      evidenced also from DSC analysis. Heat capacity data for the LS and HS phases are
      tabulated at selected temperatures, the values of the enthalpy and entropy
      changes connected with the change of spin state were reckoned at DeltaH = 12.5 +/
      0.3 kJ mol-1 and DeltaS = 33.3 +/- 0.8 J mol-1 K-1, respectively, for 1 and
      DeltaH = 6.5 +/- 0.3 kJ mol-1 and DeltaS = 17.6 +/- 0.8 J mol-1 K-1,
      respectively, for 2.

PMID- 18076160
TI  - High-valent technetium complexes with the [(99)TcO(3)](+) core from in situ
      prepared mixed anhydrides of [(99)TcO(4)](-) and their reactivities.
AB  - The highly reactive mixed anhydrides [TcO3(OCOPh)] and [TcO3(OBF3)]- were
      synthesized by treatment of [TcO4]- with strong Lewis acids benzoyl chloride and
      BF3.OEt2. These mixed anhydrides, prepared in situ, were used as precursors for
      the synthesis of complexes containing the [TcO3]+ core. Subsequent reactions with
      bi- or tridentate ligands resulted in new complexes comprised of the [TcO3]+
      core. As examples with bidentate ligands, the classical complexes [TcO3Cl(bipy)]
      (1) (bipy = 2,2'-bipyridine) and [TcO3Cl(phen)] (2) (phen = 1,10-phenanthroline)
      have been prepared by this strategy and structurally characterized. The new
      compounds [TcO3(bpza)] (3) (bpza = di-1H-pyrazol-1-ylacetate), [TcO3(bpza*)] (4)
      (bpza* = bis(3,5-dimethyl-1H-pyrazol-1-yl)acetate), [TcO3(tpzm*)]+ (6) (tpzm* =
      1,1,1-methanetriyltris(3,5-dimethyl-1H-pyrazole), and [ReO3(tpzm*)][ReO4] (7) are
      examples of complexes with tripod ligands. The complexes have been structurally
      characterized, and their 99Tc NMR spectra have been recorded. As a common
      feature, the X-ray structures show a distinct widening of the O-Tc-O angles,
      almost to a tetrahedral angle. With the perspective of radiopharmaceutical
      applications, water stability and reactivities toward alkenes are described.

PMID- 18076161
TI  - Very large difference in electronic communication of dimetal species with
      heterobiphenylene and heteroanthracene units.
AB  - Two neutral compounds having [Mo2] units linked by squarate dianions,
      [Mo2(DAniF)3]2(mu4-C4O4) (DAniF = N,N'-di(p-anisyl)formamidinate) (1) and
      [Mo2(DmCF3F)3]2(mu4-C4O4) (DmCF3F = N,N'-di(m
      trifluoromethylphenyl)formamidinate) (2), as well as the singly oxidized compound
      {[Mo2(DmCF3F)3]2(mu4-C4O4)}SbF6 (3) and the doubly oxidized species
      {[Mo2(DAniF)3]2(mu4-C4O4)}(TFPB)2 (TFPB = [B(3,5-(CF3)2C6H3)4]-) (4), were
      synthesized and structurally characterized. Electrochemical measurements of the
      two neutral species showed only very weak electronic interactions between the two
      dimolybdenum units linked by the squarate anion in contrast to what was observed
      in dioxolene analogues having C6 instead of C4 rings (J. Am. Chem. Soc. 2006,
      128, 3281) which led to differences in comproportionation constants of over 108.
      In the squarate species, the pi electrons are localized within the carbonyl and
      dimetal units in the heterometallic six-membered Mo2O2C2 rings to minimize the
      antiaromaticity in the central C4 square. The oxidized species 3 and 4 are
      electronically localized in the time scale of the physical measurements.
      Calculations at the DFT level suggested that the energy mismatch of the frontier
      orbitals of the linker and dimetal units contributes to the weak communication
      between the Mo2 units. For the doubly oxidized complex 4, DFT calculations gave a
      J value of -130 cm(-1) which suggests that the two unpaired electrons are only
      weakly antiferromagnetically coupled, as shown by magnetic studies (J = -121 cm(
      1)).

PMID- 18076162
TI  - Regulation mechanism of spin-orbit coupling in charge-transfer-induced
      luminescence of imidazopyrazinone derivatives.
AB  - The spin transition in the reactions of the derivatives of imidazo[1,2-a]pyrazin
      3(7H)-one (1H) with a triplet molecular oxygen (3O2) has been investigated by the
      geometry optimization at the B3LYP/6-31+G(d) level and the evaluation of the
      electronic matrix elements for spin-orbit coupling (SOC) using the full Pauli
      Breit SOC operator. The reductive activation for the 3O2 reaction is affected by
      the proton activity and solvent polarity of a surrounding reaction field. In a
      polar aprotic solvent, a base-prompted anionic substrate may react with 3O2 in a
      stepwise manner through complete electron transfer from the substrate anion to
      3O2, while the irreversible concerted 3O2 addition via intersystem crossing may
      become complete in a less polar solvent. SOC in the thermal decomposition of a
      resulting peroxide adduct can be controlled by the protonation state of the
      substrate. There exists an optimal protonation state for the suppression of SOC
      in the charge-transfer-induced luminescence (CTIL) of the peroxide, which is
      closely related with the ability of a substituent to donate an electron. This
      will constitute a necessary condition for the high efficiency of chemi- and
      bioluminescence.

PMID- 18076163
TI  - Interconvertable modular framework and layered lanthanide(III)-etidronic acid
      coordination polymers.
AB  - Isostructural modular microporous Na2[Y(hedp)(H2O)0.67] and
      Na4[Ln2(hedp)2(H2O)2].nH2O (Ln = La, Ce, Nd, Eu, Gd, Tb, Er) framework-type, and
      layered orthorhombic [Eu(H2hedp)(H2O)2].H2O and Na0.9[Nd0.9Ge0.10(Hhedp)(H2O)2],
      monoclinic [Ln(H2hedp)(H2O)].3H2O (Ln = Y, Tb), and triclinic [Yb(H2hedp)].H2O
      coordination polymers based on etidronic acid (H5hedp) have been prepared by
      hydrothermal synthesis and characterized structurally by (among others) single
      crystal and powder X-ray diffraction and solid-state NMR. The structure of the
      framework materials comprises eight-membered ring channels filled with Na+ and
      both free and lanthanide-coordinated water molecules, which are removed
      reversibly by calcination at 300 degrees C (structural integrity is preserved up
      to ca. 475 degrees C), denoting a clear zeolite-type behavior. Interesting
      photoluminescence properties, sensitive to the hydration degree, are reported for
      Na4[Eu2(hedp)2(H2O)2].H2O and its fully dehydrated form. The 3D framework and
      layered materials are, to a certain extent, interconvertable during the
      hydrothermal synthesis stage via the addition of HCl or NaCl: of the 3D framework
      Na4[Tb2(hedp)2(H2O)2].nH2O, affords layered [Tb(H2hedp) (H2O)].3H2O, whereas
      layered [Tb(H2hedp)(H2O)2].H2O reacts with sodium chloride yielding a material
      similar to Na4[Tb2(hedp)2(H2O)2].nH2O. In layered [Y(H2hedp)(H2O)].3H2O,
      noncoordinated water molecules are engaged in cooperative water-to-water hydrogen
      bonding interactions, leading to the formation of a (H2O)13 cluster, which is the
      basis of an unprecedented two-dimensional water network present in the interlayer
      space.

PMID- 18076164
TI  - Toward efficient nanoporous catalysts: controlling site-isolation and
      concentration of grafted catalytic sites on nanoporous materials with solvents
      and colorimetric elucidation of their site-isolation.
AB  - We report that the polarity and dielectric constants of solvents used for
      grafting organosilanes on mesoporous materials strongly affect the concentration
      of grafted organic groups, the degree of their site-isolation, and the catalytic
      properties of the resulting materials. Polar and nonpolar organosilanes as well
      as polar-protic, dipolar-aprotic, and nonpolar solvents were investigated. Polar
      protic solvents, which have high dielectric constants, resulted in smaller
      concentrations ( approximately 1-2 mmol/g) of polar organic groups such as 3
      aminopropyl groups, higher surface area materials, site-isolated organic groups,
      and more efficient catalytic properties toward the Henry reaction of p
      hydroxybenzaldehyde with nitromethane. On the other hand, dipolar-aprotic and
      nonpolar solvents resulted in larger concentrations ( approximately 2-3 mmol/g)
      of grafted polar functional groups, lower-to-higher surface area materials, more
      densely populated catalytic groups, and poor-to-efficient catalytic properties
      toward the Henry reaction. Both the polar-protic and dipolar-aprotic solvents
      resulted in significantly lower concentration of grafted groups for nonpolar
      organosilanes such as (3-mercaptopropyl)trimethoxysilane compared to
      corresponding grafting of the polar amino-organosilanes. The relationship between
      the solvent properties and the percentage and degree of site-isolation of the
      grafted functional groups was attributed to differences in solvation of the
      organosilanes and silanols in various solvents and possible hydrogen-bonding
      between the organsilanes and the solvents. The degree of site-isolation of the
      amine groups, which affect the material's catalytic properties, was elucidated by
      a new colorimetric method involving probing of the absorption maxima (lambdamax)
      on the d-d electronic spectrum of Cu2+ complexes with the amine-functionalized
      materials and the colors of the samples. The absorption lambdamax and the colors
      of the materials were found to be uniquely dependent on the type of solvents used
      for grafting the organoamines. For instance, the monoamine- and diamine
      functionalized samples grafted in methanol resulted in pale blue and light purple
      colors with lambdamax at approximately 720 and 650 nm, respectively. These
      correspond to CuNO5 and CuN2O4 structures, respectively, which are indicative of
      the presence of site-isolated organoamines in samples grafted in methanol. The
      monoamine and diamine samples grafted in toluene resulted in purple and deep
      purple colors with lambdamax at approximately 590 and 630 nm, respectively. These
      correspond to CuN2O4 and CuN4O2, which are indicative of the presence of closely
      spaced organoamines in samples grafted in toluene. The samples grafted in
      isopropanol gave colors and lambdamax intermediate between those of samples
      grafted in toluene and methanol.

PMID- 18076165
TI  - Quantum dot fluorescence quenching pathways with Cr(III) complexes.
      photosensitized NO production from trans-Cr(cyclam)(ONO)2+.
AB  - Described is the photoluminescence (PL) of water-soluble CdSe/ZnS core/shell
      quantum dots (QDs) as perturbed by salts of the chromium(III) complexes trans
      Cr(cyclam)Cl2+ (1), trans-Cr(cyclam)(ONO)2+ (2), and trans-Cr(cyclam)(CN)2+ (3)
      (cyclam = 1,4,8,11-tetraazacyclo-tetradecane). The purpose is to probe the
      characteristics of such QDs as antennae for photosensitized release of bioactive
      agents (in the present case, the bioregulatory molecule NO) from transition metal
      centers. Addition of 1 or 2 to a QD solution results in concentration-dependent
      quenching of the band edge emission, but 3 has a minimal effect. Added KCl
      strongly attenuates the quenching by 1, and this suggests that the Cr(III)
      cations and the QDs form electrostatic assemblies via ion pairing on the
      negatively charged QD surfaces. Quenching by 2, a known photochemical NO
      precursor, was accompanied by photosensitized NO release. All three, however, do
      quench the broad red emission ( approximately 650-850 nm) attributed to radiative
      decay of surface trapped carriers. The effect of various concentrations of 1 on
      time-resolved PL and absorbance were explored using ultrafast spectroscopic
      methods. These observations are interpreted in terms of the Forster resonance
      energy-transfer mechanism for quenching of the band edge PL by multiple units of
      1 or 2 at the QD surface, whereas quenching of the low-energy trap emission
      occurs via a charge-transfer pathway.

PMID- 18076166
TI  - Enantioselective alpha-arylation of ketones with aryl triflates catalyzed by
      difluorphos complexes of palladium and nickel.
AB  - The asymmetric alpha-arylation of ketones with aryl triflates is described, and
      the use of this electrophile with nickel and palladium catalysts containing a
      segphos derivative increases substantially the scope of highly enantioselective
      arylations of ketone enolates. The combination of aryl triflates as reactant,
      difluorphos as ligand, palladium catalysts for reactions of electron-neutral or
      electron-rich aryl triflates, and nickel catalysts for reactions of electron-poor
      aryl triflates led to a series of alpha-arylations of tetralone, indanone,
      cyclopentanone, and cyclohexanone derivatives. Enantioselectivities ranged from
      70% to 98% with 10 examples over 90%. Systematic studies on these alpha
      arylations have revealed a number of factors that affect enantioselectivity.
      Ligands containing biaryl backbones with smaller dihedral angles generate
      catalysts that react with higher enantioselectivity than related ligands with
      larger dihedral angles. In addition, faster rates for reactions of aryl triflates
      versus those for reactions of aryl bromides allow the alpha-arylations of aryl
      triflates to be conducted at lower temperatures, and this lower temperature
      improves enantioselectivity. Finally, studies that compare the
      enantioselectivities of catalytic reactions to those of stoichiometric reactions
      of isolated [(segphos)Pd(Ar)(Br)], [(segphos)Pd(Ar)(I)], and [(segphos)Ni(C6H4-4
      CN)Br] suggest that catalyst decomposition affects enantioselectivity.

PMID- 18076167
TI  - Two- and three-dimensional smectic ordering of single-handed helical polymers.
AB  - Rodlike polymers with precisely defined architectures are ideal building blocks
      for self-assembled structures leading to novel nanometer-scale devices. We found
      that the living polymerization of a single isocyanide enantiomer bearing an l
      alanine pendant with a long n-decyl chain simultaneously produced diastereomeric
      right- and left-handed helices with different molecular weights and narrow
      molecular weight distributions. Each single-handed, rodlike helical polymer with
      a controlled length and handedness isolated by a facile solvent fractionation
      method with acetone self-assembled to form well-defined two- and three
      dimensional smectic ordering on the nanometer scale on a substrate and in a
      liquid crystalline state as evidenced by direct atomic force microscopic
      observations and X-ray diffraction measurements, respectively.

PMID- 18076168
TI  - Target-specific chemical acylation of lectins by ligand-tethered DMAP catalysts.
AB  - Because sugar-binding proteins, so-called lectins, play important roles in many
      biological phenomena, the lectin-selective labeling should be useful for
      investigating biological processes involving lectins as well as providing
      molecular tools for analysis of saccharides and these derivatives. We describe
      herein a new strategy for lectin-selective labeling based on an acyl transfer
      reaction directed by ligand-tethered DMAP (4-dimethylaminopyridine). DMAP is an
      effective acyl transfer catalyst, which can activate an acyl ester for its
      transfer to a nucleophilic residue. To direct the acyl transfer reaction to a
      lectin of interest, we attached the DMAP to a saccharide ligand specific for the
      target lectin. It was clearly demonstrated by biochemical analyses that the
      target-selective labeling of Congerin II, an animal lectin having selective
      affinity for Lactose/LacNAc (N-acetyllactosamine), was achieved in the presence
      of Lac-tethered DMAPs and acyl donors containing probes such as fluorescent
      molecules or biotin. Conventional peptide mapping experiments using HPLC and
      tandem mass-mass analysis revealed that the acyl transfer reaction site
      specifically occurred at Tyr 51 of Cong II. This strategy was successfully
      extended to other lectins by changing the ligand part of the ligand-tethered
      DMAP. We also demonstrated that this labeling method is applicable not only to
      purified lectin in test tubes, but also to crude mixtures such as E. coli lysates
      or homogenized animal tissue samples expressing Congerin.

PMID- 18076169
TI  - Magnetic and optical bistability driven by thermally and photoinduced
      intramolecular electron transfer in a molecular cobalt-iron prussian blue
      analogue.
AB  - A soluble molecular analogue of photoresponsive Co/Fe Prussian blues is described
      within this report. As judged via a variety of spectroscopic, magnetic, and
      crystallographic methods, electron transfer within the octanuclear complex (below
      250 K) converts paramagnetic red crystals into green diamagnetic ones. The color
      and magnetic changes are associated with the transformation of FeIIILS-CN-CoIIHS
      units into FeIILS-CN-CoIIILS fragments in manner that is identical to that found
      for the An[Co(OH2)(6-6m)][Fe(CN)6]m.xH2O (An = alkali metal cation) family of
      three-dimensional Prussian blues. Moreover, this intramolecular electron transfer
      can be quantitatively circumvented via rapid thermal quenching and reversed via
      simple white light irradiation at low temperatures. Remarkably the data suggests
      that thermally or photoinduced paramagnetic metastable phases are identical and
      exhibit long relaxation times that approach 10 years at 120 K.

PMID- 18076170
TI  - Gold(I)-catalyzed intramolecular [4+2] cycloadditions of arylalkynes or 1,3
      enynes with alkenes: scope and mechanism.
AB  - The cyclizations of enynes substituted at the alkyne gives products of formal
      [4+2] cyclization with Au(I) catalysts. 1,8-Dien-3-ynes cyclize by a 5-exo-dig
      pathway to form hydrindanes. 1,6-Enynes with an aryl ring at the alkyne give
      2,3,9,9a-tetrahydro-1H-cyclopenta[b]naphthalenes by a 5-exo-dig cyclization
      followed by a Friedel-Crafts-type ring expansion. A 6-endo-dig cyclization is
      also observed in some cases as a minor process, although in a few cases, this is
      the major cyclization pathway. In addition to cationic gold complexes bearing
      bulky biphenyl phosphines, a gold complex with tris(2,6-di-tert
      butylphenyl)phosphite is exceptionally reactive as a catalyst for this reaction.
      This cyclization can also be carried out very efficiently with heating under
      microwave irradiation. DFT calculations support a stepwise mechanism for the
      cycloaddition by the initial formation of an anti-cyclopropyl gold(I)-carbene,
      followed by its opening to form a carbocation stabilized by a pi interaction with
      the aryl ring, which undergoes a Friedel-Crafts-type reaction.

PMID- 18076171
TI  - Tuning the structural and physical properties of Cr2Ti3Se8 by lithium
      intercalation: a study of the magnetic properties, investigation of ion mobility
      with NMR spectroscopy and electronic band structure calculations.
AB  - The room temperature intercalation of Cr2Ti3Se8 with butyl lithium yields a phase
      mixture of the starting material and of the new trigonal phase with composition
      Li0.4Cr0.5Ti0.75Se2. The phase pure fully intercalated trigonal phase is obtained
      at elevated temperature (80 degrees C) with the final composition
      Li0.62Cr0.5Ti0.75Se2. The line profile analysis (LPA) of the powder patterns
      shows that pronounced strain occurs in the intercalated material. The
      deintercalation of the material is realized by treatment of the fully
      intercalated sample with distilled water leading to the composition
      Li0.15Cr0.5Ti0.75Se2. The intercalation is accompanied by an electron transfer
      from the guest Li to the host material, and as a consequence significant changes
      of the interatomic distances are observed. The local environment and the dynamics
      of the Li+ ions in the fully intercalated sample were studied with 7Li magic
      angle spinning (MAS) NMR investigations. These reveal different environments of
      transition metal neighbors for the Li sites and a high mobility of the Li ions.
      Magnetic measurements show that in the pristine material antiferromagnetic
      interactions are dominating (theta = -113.5 K) with no long-range order at low
      temperatures. The magnetic ground state is characterized by a spin-glass
      behavior. With increasing Li content the antiferromagnetic character vanishes
      progressively, and the fully intercalated phase exhibits a positive Weiss
      constant (theta = 12 K) indicating dominating ferromagnetic exchange
      interactions; i.e., the magnetic properties can be significantly altered by
      lithiation. The interpretation of our experimental findings is supported by the
      results of accompanying band structure calculations done within the framework of
      local spin density functional theory. These demonstrate in particular the role of
      the charge transfer between the constituents as a function of the Li
      concentration and its impact on the exchange coupling.

PMID- 18076172
TI  - Charge transport in single Au / alkanedithiol / Au junctions: coordination
      geometries and conformational degrees of freedom.
AB  - Recent STM molecular break-junction experiments have revealed multiple series of
      peaks in the conductance histograms of alkanedithiols. To resolve a current
      controversy, we present here an in-depth study of charge transport properties of
      Au|alkanedithiol|Au junctions. Conductance histograms extracted from our STM
      measurements unambiguously confirm features showing more than one set of junction
      configurations. On the basis of quantum chemistry calculations, we propose that
      certain combinations of different sulfur-gold couplings and trans/gauche
      conformations act as the driving agents. The present study may have implications
      for experimental methodology: whenever conductances of different junction
      conformations are not statistically independent, the conductance histogram
      technique can exhibit a single series only, even though a much larger abundance
      of microscopic realizations exists.

PMID- 18076173
TI  - X-ray absorption spectroscopic and theoretical studies on (L)2[Cu2(S2)n]2+
      complexes: disulfide versus disulfide(*1-) bonding.
AB  - Cu K-, Cu L-, and S K-edge X-ray absorption spectroscopic (XAS) data have been
      combined with density functional theory (DFT) calculations on
      [{(TMPA)Cu}2S2](ClO4)2 (1), [{Cu[HB(3,5-Pr(i)2pz)3]}2(S2)] (2), and
      [{(TMEDA)Cu}2(S2)2](OTf)2 (3) to obtain a quantitative description of their
      ground state wavefunctions. The Cu L-edge intensities give 63 and 37% Cu d
      character in the ground state of 1 and 2, respectively, whereas the S K-pre-edge
      intensities reflect 20 and 48% S character in their ground states, respectively.
      These data indicate a more than 2-fold increase in the total disulfide bonding
      character in 2 relative to 1. The increase in the number of Cu-S bonds in 2 (mu
      eta(2):eta(2) S2(2-) bridge) compared to 1 ((mu-eta(1):eta(1) S2(2-) bridge)
      dominantly determines the large increase in covalency and Cu-disulfide bond
      strength in 2. Cu K- and L- and S K-pre-edge energy positions directly
      demonstrate the Cu(II)/(S2(-))2 nature of 3. The two disulfide(*1-)'s in 3
      undergo strong bonding interactions that destabilize the resultant filled
      antibonding pi* orbitals of the (S2(-))2 fragment relative to the Cu 3d levels.
      This leads to an inverted bonding scheme in 3 with dominantly ligand-based holes
      in its ground state, consistent with its description as a dicopper(II)-bis
      disulfide(*1-) complex.

PMID- 18076174
TI  - Cholesterol shows preference for the interior of polyunsaturated lipid membranes.
AB  - Recent neutron scattering experiments showed a striking manifestation of the
      aversion between polyunsaturated fatty acid (PUFA)-containing lipids and
      cholesterol. Selectively deuterated cholesterol/ 1,2
      diarachidonylphosphatidylcholine (DAPC) samples revealed that the hydroxyl of the
      sterol resides at the center of the bilayer. Here we use a recently parametrized
      coarse grain simulation model to shed light on these puzzling experimental
      observations. Using a simulation setup in close correspondence to the
      experimental conditions, we reproduce the experimental neutron scattering
      profiles to a large extent. The simulations allow us to analyze the behavior of
      cholesterol in detail; we show that the interaction of cholesterol with the PUFA
      chains of DAPC leads to a fast flip-flop rate for the sterol and an increased
      preference of the sterol for the unusual location embedded between the monolayer
      leaflets.

PMID- 18076175
TI  - Enantioselective, organocatalytic oxy-michael addition to gamma/delta-hydroxy
      alpha,beta-enones: boronate-amine complexes as chiral hydroxide synthons.
AB  - An organocatalytic, enantioselective oxy-Michael addition to achiral gamma- and
      delta-hydroxy-alpha,beta-enones was developed. The key transformation is an
      unprecedented, asymmetric conjugate addition triggered by complexation between an
      in situ generated boronic acid hemiester and a chiral amine catalyst.
      Functionally, the intermediate amine-boronate complex acts as a chiral hydroxide
      surrogate or synthon. The resultant chiral beta-hydroxy-ketones are obtained in
      good to excellent yields and high ee following mild oxidative removal of the
      cyclic boronate. Natural products (R,12Z,15Z)-2-hydroxy-4-oxohenicosa-12,15
      dienyl acetate and (+)-(S)-streptenol A were synthesized to demonstrate the
      utility of this reaction.

PMID- 18076176
TI  - Synthesis, characterization, and marked polymerization selectivity
      characteristics of binuclear phenoxyiminato organozirconium catalysts.
AB  - The new binuclear phenoxyiminato zirconium complex {1,7-(O)2C10H4-2,7-[CH=N(2,6
      iPr2C6H3)]2}Zr2Cl6(THF)2 (FI2-Zr2) polymerizes ethylene with greater activity
      (approximately 8x) than the mononuclear analogue. Also, this catalyst produces
      high molecular weight ethylene + 1-hexene copolymers, while the mononuclear
      analogue yields only traces of copolymer under identical conditions. This ability
      to produce copolymers suggests cooperativity between the two Zr centers which
      promotes 1-hexene co-enchainment.

PMID- 18076177
TI  - Highly chemoselective metal-free reduction of tertiary amides.
AB  - This communication describes the chemoselective metal-free reduction of tertiary
      amides to the corresponding amines. Hantzsch ester is used as a mild reducing
      agent for the reduction of trifluoromethanesulfonic anhydride activated amides
      providing the tertiary amines with high functional group tolerance.

PMID- 18076178
TI  - Giant coercivity in a one-dimensional cobalt-radical coordination magnet.
AB  - A metal-radical polymer [Co(hfac)2.BPNN] showed a very large coercive field of 52
      kOe (4.1 MA m-1) at 6 K, indicating that it is the hardest magnet ever reported.
      Above 10 K, a soft character appeared, owing to the fast dynamics of
      magnetization reorientation.

PMID- 18076179
TI  - The role of colloid formation in the photoinduced H2 production with a Ru(II)
      Pd(II) supramolecular complex: a study by GC, XPS, and TEM.
AB  - The dinuclear RuII-PdII complex shows efficient H2 production in the presence of
      triethylamine as a sacrificial electron and proton donor under visible light
      irradiation. XPS and TEM analyses reveal that photoreduction of PdII to Pd0
      causes dissociation of Pd from the complex to form colloids that are suggested to
      be the actual catalyst for H2 production.

PMID- 18076180
TI  - Superparamagnetic high-magnetization microspheres with an Fe3O4@SiO2 core and
      perpendicularly aligned mesoporous SiO2 shell for removal of microcystins.
AB  - Superparamagnetic microspheres with an Fe3O4@SiO2 core and a perpendicularly
      aligned mesoporous SiO2 shell were synthesized through a surfactant-templating
      sol-gel approach. The microspheres possess high magnetization (53.3 emu/g), high
      surface area (365 m2/g), large pore volume (0.29 cm3/g), and uniform mesopore
      (2.3 nm). By using the unique core-shell microspheres with accessible large pores
      and excellent magnetic property, a fast removal of microcystins with high
      efficiency (>95%) can be achieved.

PMID- 18076181
TI  - Highly efficient asymmetric synthesis of fluvirucinine A1 via Zr-catalyzed
      asymmetric carboalumination of alkenes (ZACA)-lipase-catalyzed acetylation tandem
      process.
AB  - ZACA-lipase-catalyzed acetylation tandem process has been shown to proceed
      satisfactorily with either TBS-protected 4-penten-1-ol or 3-buten-1-ol to provide
      the corresponding enantiomerically pure (R)-2-ethyl-1-alkanols. Either (R)-5 or
      (R)-6 was converted to 3 in seven steps. The other fragment 4 was synthesized in
      nine steps from (-)-(S)-citronellol. Conversion of 3 and 4 into 99% pure
      fluvirucinine A1 was achieved in four steps via amidation-ring closing
      metathesis, the overall yield in the longest linear sequence being 34% (13
      steps).

PMID- 18076182
TI  - Selective synthesis of secondary and tertiary amines by cp*iridium-catalyzed
      multialkylation of ammonium salts with alcohols.
AB  - The efficient selective synthesis of secondary and tertiary amines has been
      achieved by means of Cp*Ir-catalyzed multialkylation of ammonium salts with
      alcohols without solvent: the reactions of ammonium acetate with alcohols gave
      tertiary amines exclusively, while those of ammonium tetrafluoroborate afforded
      secondary amines selectively. Using this method, secondary 5- and 6-membered
      cyclic amines were synthesized from ammonium tetrafluoroborate and diols in one
      pot.

PMID- 18076183
TI  - Synthesis of modified DNA by PCR with alkyne-bearing purines followed by a click
      reaction.
AB  - Alkyne-bearing deazapurine triphosphates were prepared and successfully
      incorporated into DNA using the polymerase chain reaction (PCR). The obtained
      alkyne-labeled DNA was successfully used in a click reaction with galactose
      azide.

PMID- 18076184
TI  - Total synthesis of (3R,9R,10R)-panaxytriol via tandem metathesis and
      metallotropic [1,3]-shift as a key step.
AB  - Enyne metathesis is unique for its capacity to carry out multiple bond formation
      in tandem fashion. Its combined use with metallotropic [1,3]-shift allowed for
      the development of a novel strategy for the total synthesis of a conjugated 1,3
      diyne-containing natural product (3R,9R,10R)-panaxytriol.

PMID- 18076185
TI  - Regulation of cyclization for the stereoselective synthesis of substituted
      tetrahydrofurans and tetrahydrooxepines.
AB  - Dramatic solvent effect is observed during the cyclization of 1. Synthesis of 2
      is achieved from the reaction of 1 with a hexamethylditin-catalyzed palladium
      complex followed by aldehydes in the presence of TMSOTf in THF, whereas 3 is
      formed in CH2Cl2. The method described herein is successful with various
      substrates 1 in good yields and high levels of diastereoselectivity.

PMID- 18076186
TI  - Synthesis and conformational studies of peptidomimetics containing a new
      bifunctional diketopiperazine scaffold acting as a beta-hairpin inducer.
AB  - A practical synthesis of a new bifunctional diketopiperazine (DKP) scaffold 1,
      formally derived from the cyclization of L-aspartic acid and (S)-2,3
      diaminopropionic acid, is reported. DKP-1 bears a carboxylic acid and an amino
      functionalities in a cis relationship, which have been used to grow peptide
      sequences. Tetra-, penta-, and hexapeptidomimetic sequences were prepared by
      solution-phase peptide synthesis (Boc strategy). Conformational analysis of these
      derivatives was carried out by a combination of 1H NMR spectroscopy, IR
      spectroscopy, CD spectroscopy, and computer modeling, and reveals the formation
      of beta-hairpin mimics involving 10-membered and 18-membered H-bonded rings and a
      reverse turn of the growing peptide chain.

PMID- 18076187
TI  - One-electron oxidation of 2-(4-methoxyphenyl)-2-methylpropanoic and 1-(4
      methoxyphenyl)cyclopropanecarboxylic acids in aqueous solution. the involvement
      of radical cations and the influence of structural effects and pH on the side
      chain fragmentation reactivity.
AB  - A product and time-resolved kinetic study on the one-electron oxidation of 2-(4
      methoxyphenyl)-2-methylpropanoic acid (2), 1-(4
      methoxyphenyl)cyclopropanecarboxylic acid (3), and of the corresponding methyl
      esters (substrates 4 and 5, respectively) has been carried out in aqueous
      solution. With 2, no direct evidence for the formation of an intermediate radical
      cation 2*+ but only of the decarboxylated 4-methoxycumyl radical has been
      obtained, indicating either that 2*+ is not formed or that its decarboxylation is
      too fast to allow detection under the experimental conditions employed (k > 1 x
      10(7) s(-1)). With 3, oxidation leads to the formation of the corresponding
      radical cation 3*+ or radical zwitterion -3*+ depending on pH. At pH 1.0 and 6.7,
      3*+ and -3*+ have been observed to undergo decarboxylation as the exclusive side
      chain fragmentation pathway with rate constants k = 4.6 x 10(3) and 2.3 x 10(4)
      s(-1), respectively. With methyl esters 4 and 5, direct evidence for the
      formation of the corresponding radical cations 4*+ and 5*+ has been obtained.
      Both radical cations have been observed to display a very low reactivity and an
      upper limit for their decay rate constants has been determined as k < 10(3) s(
      1). Comparison between the one-electron oxidation reactions of 2 and 3 shows that
      the replacement of the C(CH3)2 moiety with a cyclopropyl group determines a
      decrease in decarboxylation rate constant of more than 3 orders of magnitude.
      This large difference in reactivity has been qualitatively explained in terms of
      three main contributions: substrate oxidation potential, stability of the carbon
      centered radical formed after decarboxylation, and stereoelectronic effects. In
      basic solution, -3*+ and 5*+ have been observed to react with -OH in a process
      that is assigned to the -OH-induced ring-opening of the cyclopropane ring, and
      the corresponding second-order rate constants (k-OH) have been obtained. With 
      3*+, competition between decarboxylation and -OH-induced cyclopropane ring
      opening is observed at pH >or=10, with the latter process that becomes the major
      fragmentation pathway around pH 12.

PMID- 18076188
TI  - Trimethylsilyl trifluoromethanesulfonate (TMSOTf) assisted facile deprotection of
      N,O-acetonides.
AB  - Employing TMSOTf as an easily available reagent, we have developed a mild and
      efficient method for the deprotection of both terminal and internal N,0-acetonide
      functionalities. Various regularly used protecting groups and common organic
      functional moieties were found to be unaffected by the described reaction
      conditions. In a few representative examples, the present method was also
      extended to deprotect acetonides obtained from 1,2-, and 1,3-terminal diols. The
      acetonide deprotection protocol described herein is expected to be a useful
      addition to the presently available methods for performing the above
      transformation.

PMID- 18076189
TI  - Highly efficient photochemically induced thiyl radical-mediated racemization of
      aliphatic amines at 30 degrees C.
AB  - UV irradiation in the presence of thiol enables the performance of highly
      efficient aliphatic amines racemization, under mild conditions at 30 degrees C.
      The reaction proceeds via the reversible generation of prochiral alpha-aminoalkyl
      radicals. The latter may result either from a redox process between the thiyl
      radical and the amine or from direct hydrogen atom abstraction by thiyl radical.
      As hydrogen atom donor, the thiol plays a crucial role. While the racemization of
      both primary and secondary amines were fast processes, the racemization of
      tertiary amines was sluggish. A tentative rationale is based on the
      photostimulated amine-catalyzed oxidation of the thiol into the corresponding
      disulfide, which makes the hydrogen atom donor concentration in the reaction
      medium drop up to trace amount at a rate that depends on the nature of the amine.

PMID- 18076190
TI  - Synthesis of functionalized furans via gold(I)-catalyzed Claisen-type
      rearrangement.
AB  - Gold(I)-catalyzed cyclization of pentenynyl allyl ethers allows the rapid
      construction of functionalized furans. The concerted oxy-Claisen-type mechanism
      induces a complete selectivity of the process and allows the easy formation of
      quaternary centers.

PMID- 18076191
TI  - Concise assembly of highly substituted furan-fused 1,4-thiazepines and their
      Diels-Alder reactions with benzynes.
AB  - A facile and highly efficient three-component reaction of thiazole or
      benzothiazole carbenes, disubstituted ketenes, and activated alkynes is
      disclosed. With this methodology, a polysubstituted ring system containing
      furo[2,3-c]thiazepine core can be constructed from simple and readily accessible
      starting materials in good yields. The scope and limitation of this
      transformation were investigated in detail by using various thiazole carbene,
      ketene, and alkyne components. Furthermore, the synthetic utilities of these
      unique polyheterocyclic compounds were demonstrated via their Diels-Alder
      reactions with benzynes to furnish thiazepine-fused 7-oxanorbornadiene
      derivatives in excellent yields.

PMID- 18076192
TI  - Rapid and mild synthesis of functionalized naphthalenediimides.
AB  - Core-substituted naphthalenediimides (NDIs) are not often used in functional
      materials despite excellent properties because the harsh conditions used for
      their synthesis are incompatible with structural diversity. Here, we report rapid
      access to blue, red, and yellow NDIs under mild conditions with tolerance toward
      the additional presence of pertinent functional groups.

PMID- 18076193
TI  - Core residue replacements cause coiled-coil orientation switching in vitro and in
      vivo: structure-function correlations for osmosensory transporter ProP.
AB  - Protein ProP acts as an osmosensory transporter in diverse bacteria. C-Terminal
      residues 468-497 of Escherichia coli ProP (ProPEc) form a four-heptad homodimeric
      alpha-helical coiled coil. Arg 488, at a core heptad a position, causes it to
      assume an antiparallel orientation. Arg in the hydrophobic core of coiled coils
      is destabilizing, but Arg 488 forms stabilizing interstrand salt bridges with Asp
      475 and Asp 478. Mutation R488I destabilizes the coiled coil and elevates the
      osmotic pressure at which ProPEc activates. It may switch the coiled-coil
      orientation to parallel by eliminating the salt bridges and increasing the
      hydrophobicity of the core. In this study, mutations D475A and D478A, which
      disrupt the salt bridges without increasing the hydrophobicity of the coiled-coil
      core, had the expected modest impacts on the osmotic activation of ProPEc. The
      five-heptad coiled coil of Agrobacterium tumefaciens ProP (ProPAt) has K498 and
      R505 at a positions. Mutation K498I had little effect on the osmotic activation
      of ProPAt, and ProPAt-R505I was activated only at high osmotic pressure; on the
      other hand, the double mutant was refractory to osmotic activation. Both a
      synthetic peptide corresponding to ProPAt residues 478-516 and its K498I variant
      maintained the antiparallel orientation. The single R505I substitution created an
      unstable coiled coil with little orientation preference. Double mutation
      K498I/R505I switched the alignment, creating a stable parallel coiled coil. In
      vivo cross-linking showed that the C-termini of ProPAt and ProPAt-K498I/R505I
      were antiparallel and parallel, respectively. Thus, the antiparallel orientation
      of the ProP coiled coil is contingent on Arg in the hydrophobic core and
      interchain salt bridges. Two key amino acid replacements can convert it to a
      stable parallel structure, in vitro and in vivo. An intermolecular antiparallel
      coiled coil, present on only some orthologues, lowers the osmotic pressure
      required to activate ProP. Formation of a parallel coiled coil renders ProP
      inactive.

PMID- 18076194
TI  - Bilayer and trilayer crystalline formation by collapsing behenic acid monolayers
      at gas/aqueous interfaces.
AB  - X-ray reflectivities and grazing incidence X-ray diffractions of behenic acid
      (BA) monolayers compressed to the collapse region reveal that the resulting
      structures are reproducible and exhibit a high degree of order. The structures of
      the collapsed monolayers depend on the subphase solution. On pure water, the
      collapsed monolayer forms a stable crystalline trilayer structure. For monolayers
      spread on Ca2+ solutions, we find that an inverted bilayer structure is formed;
      that is, stretched BA-Ca-BA (calcium dibehenate, with calcium ions bridging the
      polar headgroups) forms a monolayer with the hydrophobic tails in contact with
      the water surface.

PMID- 18076195
TI  - Ambiguity in determining the shape of alkali alkyl sulfate micelles from small
      angle scattering data.
AB  - Model fitting to small-angle scattering patterns from a series of dilute sodium-
      and cesium alkyl sulfate micellar solutions results in two significantly
      different sets of best-fit parameters for each solution. One of the sets defines
      nearly monodisperse prolate ellipsoids; the other defines slightly, but
      significantly, polydisperse oblate ellipsoids. In the prolate and oblate minimum
      locations, the mean form and structure factors as well as the mean core volumes
      are equal within the experimental error such that the axial ratios are
      approximately the reciprocals of each other. The experimental finding is
      numerically generalized: it is demonstrated that, in a Q range, the upper limit
      of which depends on the axial ratio, the squared mean and the mean square of the
      scattering amplitude from homogeneous ellipsoids with equatorial radii and axial
      ratios, respectively (r,eta) and (reta2/3,1/eta), are indistinguishable in
      practice. In dilute solutions without added salt, neither the best-fit values of
      the model parameters nor the available thermodynamic models provide direct
      evidence for the conformation, although the prolate ellipsoidal shape is
      indirectly supported by experiment. The elongated conformation of ionic micelles
      in dense and/or salinated systems seems realistic.

PMID- 18076196
TI  - Desorption-limited mechanism of release from polymer nanofibers.
AB  - This work examines the release of a model water-soluble compound from electrospun
      polymer nanofiber assemblies. Such release attracts attention in relation to
      biomedical applications, such as controlled drug delivery. It is also important
      for stem cell attachment and differentiation on biocompatible electrospun
      nanofiber scaffolds containing growth factors, which have been encapsulated by
      means of electrospinning. Typically, the release mechanism has been attributed to
      solid-state diffusion of the encapsulated compound from the fibers into the
      surrounding aqueous bath. Under this assumption, a 100% release of the
      encapsulated compound is expected in a certain (long) time. The present work
      focuses on certain cases where complete release does not happen, which suggests
      that solid-state diffusion may not be the primary mechanism at play. We show that
      in such cases the release rate can be explained by desorption of the embedded
      compound from nanopores in the fibers or from the outer surface of the fibers in
      contact with the water bath. After release, the water-soluble compound rapidly
      diffuses in water, whereas the release rate is determined by the limiting
      desorption stage. A model system of Rhodamine 610 chloride fluorescent dye
      embedded in electrospun monolithic poly(methylmethacrylate) (PMMA) or
      poly(caprolactone) (PCL) nanofibers, in nanofibers electrospun from PMMA/PCL
      blends, or in core-shell PMMA/PCL nanofibers is studied. Both the experimental
      results and theory point at the above mentioned desorption-related mechanism, and
      the predicted characteristic time, release rate, and effective diffusion
      coefficient agree fairly well with the experimental data. A practically important
      outcome of this surface release mechanism is that only the compound on the fiber
      and pore surfaces can be released, whereas the material encapsulated in the bulk
      cannot be freed within the time scales characteristic of the present experiments
      (days to months). Consequently, in such cases, complete release is impossible. We
      also demonstrate how the release rate can be manipulated by the polymer content
      and molecular weight affecting nanoporosity and the desorption enthalpy, as well
      as by the nanofiber structure (monolithic fibers, fibers from polymer blends, and
      core-shell fibers). In particular, it is shown that, by manipulating the above
      parameters, release times from tens of hours to months can be attained.

PMID- 18076197
TI  - Polymeric brushes as functional templates for immobilizing ribonuclease A: study
      of binding kinetics and activity.
AB  - The ability to immobilize proteins with high binding capacities on surfaces while
      maintaining their activity is critical for protein microarrays and other
      biotechnological applications. We employed poly(acrylic acid) (PAA) brushes as
      templates to immobilize ribonuclease A (RNase A), which is commonly used to
      remove RNA from plasmid DNA preparations. The brushes are grown by surface
      anchored atom-transfer radical polymerization (ATRP) initiators. RNase A was
      immobilized by both covalent esterification and a high binding capacity metal-ion
      complexation method to PAA brushes. The polymer brushes immobilized 30 times more
      enzyme compared to self-assembled monolayers. As the thickness of the brush
      increases, the surface density of the RNase A increases monotonically. The
      immobilization was investigated by ellipsometry, X-ray photoelectron spectroscopy
      (XPS), thermogravimetric analysis (TGA), and near-edge X-ray absorption fine
      structure spectroscopy (NEXAFS). The activity of the immobilized RNase A was
      determined using UV absorbance. As much as 11.0 microg/cm(2) of RNase A was bound
      to PAA brushes by metal-ion complexation compared to 5.8 microg/cm(2) by covalent
      immobilization which is 30 and 16 times the estimated mass bound in a monolayer.
      The calculated diffusion coefficient D was 0.63 x 10(-14) cm(2)/s for metal-ion
      complexation and 0.71 x 10(-14) cm(2)/s for covalent immobilization. Similar
      values of D indicate that the binding kinetics is similar, but the thermodynamic
      equilibrium coverage varies with the binding chemistry. Immobilization kinetics
      and thermodynamics were characterized by ellipsometry for both methods. A maximum
      relative activity of 0.70-0.80 was reached between five and nine monolayers of
      the immobilized enzyme. However, the relative activity for covalent
      immobilization was greater than that of metal-ion complexation. Covalent
      esterification resulted in similar temperature dependence as free enzyme, whereas
      metal-ion complexation showed no temperature dependence indicating a significant
      change in conformation.

PMID- 18076198
TI  - Novel photoluminescence properties of surface-modified nanocrystalline zinc
      oxide: toward a reactive scaffold.
AB  - Nanocrystalline zinc oxide has been functionalized with 11-triethoxysilylundecal
      to introduce chemical reactivity for subsequent molecular attachment while
      preserving its unique photoluminescence (PL) properties. Silane bonding is
      confirmed using FTIR and photoelectron spectroscopy, with a total Si
      concentration of 3 to 4 atomic %. PL measurements demonstrate a 2-fold
      enhancement of its UV peak and maintenance of its visible peak compared to
      control samples. Enhancement of the UV peak is likely due to a decrease in the
      surface-dependent nonradiative recombination process. These results lay the
      framework for sensor fabrication, with the aldehyde groups available to bind
      analytes that would alter the PL spectrum.

PMID- 18076199
TI  - Patchy particles by glancing angle deposition.
AB  - The application of glancing angle deposition (GLAD) as a means to produce patchy
      particles is reported. Shadow effects are caused by neighboring particles within
      the particle monolayer. The patch geometry is determined by the angle of
      incidence of the vapor rays and the monolayer orientation. A mathematical model
      is used to study the patch geometry and to calculate the area of the patch. The
      smallest patch produced with GLAD is 3.7% of the particle surface.

PMID- 18076200
TI  - Unprecedented covalently attached ATRP initiator onto OH-functionalized mica
      surfaces.
AB  - Mica substrates were activated by a plasma method leading to OH-functionalized
      surfaces to which an atom transfer radical polymerization (ATRP) radical
      initiator was covalently bound using standard siloxane protocols. The
      unprecedented covalently immobilized initiator underwent radical polymerization
      with tert-butyl acrylate, yielding for the first time end-grafted polymer brushes
      that are covalently linked to mica. The initiator grafting on the mica substrate
      was confirmed by time-of-flight secondary ion mass spectrometry (TOF-SIMS), while
      the change in the water contact angle of the OH-activated mica surface was used
      to follow the change in surface coverage of the initiator on the surface. The
      polymer brush and initiator film thicknesses relative to the virgin mica were
      confirmed by atomic force microscopy (AFM). This was done by comparing the atomic
      step-height difference between a protected area of freshly cleaved mica and a
      zone exposed to plasma activation, initiator immobilization, and then ATRP.

PMID- 18076202
TI  - Nature of sub-band gap luminescent eigenmodes in a ZnO nanowire.
AB  - The emission spectrum of individual high-quality ZnO nanowires consists of a
      series of Fabry-Perot-like eigenmodes that extend far below the band gap of ZnO.
      Spatially resolved luminescence spectroscopy shows that light is emitted
      predominantly at both wire ends, with identical spectra reflecting standing wave
      polariton eigenmodes. The intensity of the modes increases supralinearly with the
      excitation intensity, indicating that the mode population is governed by
      scattering among polaritons. Due to strong light-matter interaction, light
      emission from a ZnO nanowire is not dictated by the electronic band diagram of
      ZnO but depends also on the wire geometry and the excitation intensity.
      Delocalized polaritons provide a natural explanation for the pronounced
      subwavelength guiding in ZnO wires that has been reported previously.

PMID- 18076201
TI  - Smart hydrogel particles: biomarker harvesting: one-step affinity purification,
      size exclusion, and protection against degradation.
AB  - Disease-associated blood biomarkers exist in exceedingly low concentrations
      within complex mixtures of high-abundance proteins such as albumin. We have
      introduced an affinity bait molecule into N-isopropylacrylamide to produce a
      particle that will perform three independent functions within minutes, in one
      step, in solution: (a) molecular size sieving, (b) affinity capture of all
      solution-phase target molecules, and (c) complete protection of harvested
      proteins from enzymatic degradation. The captured analytes can be readily
      electroeluted for analysis.

PMID- 18076203
TI  - Correlated random telegraph signal and low-frequency noise in carbon nanotube
      transistors.
AB  - A correlated random telegraph signal is observed from the interaction of two
      individual defects in a carbon nanotube transistor. It is shown that the
      amplitude fluctuation of one defect significantly depends on the state of the
      other defect. Moreover, statistics of the correlated switchings is shown to
      deviate from the ideal Poisson process. Physics of this random telegraph signal
      correlation is attributed to the fact that the two defects are located closer
      than the sum of their Fermi-Thomas screening lengths. This work brings new
      implications to the source of low frequency noise in nanodevices. Moreover,
      statistic studies provide a new avenue to study correlated effects due to
      particle interactions.

PMID- 18076204
TI  - Reversible switching among three adsorbate configurations in a single
      [2.2]paracyclophane-based molecule.
AB  - Single 4,7,12,15-tetrakis(4'-dimethylaminostyryl)[2.2]paracyclophane molecules
      adsorb on NiAl(110) in different configurations. When the symmetry axes of the
      molecules are properly oriented with respect to the surface lattice, three
      adsorbate states of different conductance can be reversibly induced and directly
      imaged with a scanning tunneling microscope. Couplings between tunneling
      electrons and adsorbate vibrational and electronic states are primarily
      responsible for the transformation. However, change from low to high conductance
      configuration can also be triggered by electric field in the junction.

PMID- 18076206
TI  - The therapeutic potential of VEGF inhibition in diabetic microvascular
      complications.
AB  - During the last few years, the incidence of microvascular complications in
      diabetes mellitus has rapidly increased as a consequence of both an increase in
      incidence of type 2 and type 1 diabetes mellitus. The pathogenesis of diabetic
      microvascular complications is still largely unknown. Among the many hypotheses,
      a dysfunction in angiogenesis has been suggested as a common origin for
      retinopathy, nephropathy, and neuropathy. Based on this hypothesis, inhibition of
      vascular endothelial growth factor (VEGF) has been tested as a potential
      therapeutic approach to prevent and cure diabetic microvascular complications.
      Several VEGF inhibitors are currently under evaluation or are approved for the
      treatment of wet age-related macular degeneration and macular edema. These
      include inhibitors of intracellular transcription of VEGF (e.g. bevasiranib),
      inhibitors of extracellular VEGF (e.g. pegaptanib), inhibitors of VEGF receptor
      expression (e.g. aflibercept [VEGF-TRAP]) and inhibitors of the intracellular
      signaling cascade activating VEGF (e.g. midostaurin). According to the existing
      evidence base, although inhibition of VEGF results in a better outcome in the
      case of diabetic retinopathy and also, despite some discrepant results, in the
      case of diabetic nephropathy, there is no final confirmation that VEGF inhibition
      is a valid approach for diabetic neuropathy. The latter complication actually, in
      line with other chronic neuropathies, seems to improve with stimulation of
      angiogenesis through increased expression of VEGF.

PMID- 18076207
TI  - Current management of syncope : focus on drug therapy.
AB  - Syncope is defined as transient loss of consciousness as a result of inadequate
      cerebral perfusion. The causes of syncope fall into five broad categories:
      neurally mediated, orthostatic (the most frequent causes), cardiac arrhythmias,
      structural cardiovascular (relatively uncommon cause), and cerebrovascular (very
      rare). The initial evaluation of the syncope patient includes a detailed medical
      history and physical exam, and usually an ECG and echocardiogram. Thereafter,
      selected additional testing (e.g. ambulatory ECG recording, autonomic function
      testing, electrophysiologic study) may be needed on a case-by-case basis.
      Neurally mediated and orthostatic syncope should first be treated by conservative
      therapies including hydration/volume expanders and physical counter-maneuvers.
      Various drugs may play a role as second-line of treatment. However, apart from
      midodrine, randomized studies of drug therapy are largely lacking, and most
      agents have not proved to be predictably effective. For syncope due to cardiac
      arrhythmias, treatment options (depending on the specific circumstance) include
      ablation of the arrhythmia origin, antiarrhythmic drugs, and/or implantable
      devices (pacemakers and defibrillators). In the case of syncope due to structural
      cardiovascular defects (e.g. acute myocardial ischemia, pulmonary hypertension,
      obstructive cardiomyopathy), treatment is aimed at ameliorating the underlying
      structural defect. In brief, establishing a specific cause(s) for syncope is
      crucial. Only then can a potentially effective treatment strategy be
      contemplated.

PMID- 18076208
TI  - Fixed-dose combination antihypertensives and reduction in target organ damage:
      are they all the same?
AB  - Hypertension is a multifactorial disorder leading to pathophysiologic changes in
      target organs over time through diverse mechanisms. In addition, hypertension
      frequently resists control with monotherapy, necessitating combination therapy
      with two or more antihypertensive agents. Many currently available fixed-dose
      antihypertensive combinations combine drugs with different, but complementary,
      mechanisms of action to improve overall efficacy and tolerability. In addition,
      it is possible to select drug combinations whereby one drug offsets the negative
      effects of the other drug. Fixed-dose antihypertensive combinations may provide
      significant advantages over high-dose monotherapy, such as improved BP-lowering
      efficacy, reduced adverse event frequency, improved patient compliance,
      potentially lower treatment costs, and shorter time to BP control. Combination
      therapy has been recommended as potential first-line therapy in recent consensus
      guideline statements, especially for higher-risk patients, such as those with
      stage 2 hypertension. The combination of a renin-angiotensin-aldosterone system
      targeting agent, such as an ACE inhibitor or angiotensin II receptor antagonist
      (ARB), and a diuretic or calcium channel antagonist appears to provide synergy
      with regard to BP lowering. In addition, ACE inhibitors and ARBs have
      demonstrated beneficial effects beyond BP reduction, reducing cardiovascular
      morbidity and mortality, inhibiting development and progression of type 2
      diabetes mellitus and the progression of renal disease. Preliminary studies of
      fixed-dose combinations have shown reductions in left ventricular hypertrophy and
      improvements in markers of renal function. Additional studies currently underway
      will compare the effects of available fixed-dose combinations on cardiovascular
      morbidity and mortality, and markers of renal dysfunction.

PMID- 18076209
TI  - ADP receptor antagonism: what's in the pipeline?
AB  - ADP is one of the most important mediators of both physiologic hemostasis and
      thrombosis. Development and utilization of agents that block ADP receptors on the
      platelet membrane, namely thienopyridines, has represented a major advancement
      for treatment of patients undergoing percutaneous coronary interventions and
      those with acute coronary syndromes. Currently, clopidogrel, a second-generation
      thienopyridine that inhibits the ADP P2Y(12) receptor, represents the treatment
      of choice, in addition to aspirin, for the prevention of stent thrombosis.
      Further, long-term adjunctive use of this ADP P2Y(12) receptor antagonist is also
      associated with improved clinical outcomes in high-risk patients, and represents
      the standard of care for these patients. Despite the unambiguous clinical benefit
      associated with clopidogrel, accumulating experience with this drug has also led
      to identification of some of its drawbacks, which are related to inadequate
      platelet inhibition with standard dosage regimens as well as to its irreversible
      antiplatelet effects. This has led to the questioning of currently recommended
      clopidogrel dosage regimens as well as to the development of novel and more
      potent ADP P2Y(12) receptor antagonists, some of which are also reversible
      agents. Numerous studies are currently ongoing with the objective of
      demonstrating how more potent platelet inhibition using higher loading and
      maintenance dose regimens of clopidogrel or novel ADP P2Y(12) receptor
      antagonists - such as prasugrel, ticagrelor (AZD 6140) and cangrelor - will
      affect clinical outcomes. This article reviews the current knowledge of platelet
      ADP P2Y(12) receptor antagonism and the projected developments in this field.

PMID- 18076210
TI  - Expression of platelet surface receptors and early changes in platelet function
      in patients with STEMI treated with abciximab and clopidogrel versus clopidogrel
      alone.
AB  - BACKGROUND: Platelets play a crucial role in the pathogenesis of acute coronary
      syndromes (ACS). The efficacy of antiplatelet treatment is pivotal in the success
      of percutaneous coronary intervention (PCI) performed in patients with ACS.
      OBJECTIVE: The aim of the study was to investigate the effects of clopidogrel
      with or without abciximab on the expression of platelet surface receptors and
      platelet function in patients with ST-segment elevation myocardial infarction
      (STEMI) undergoing PCI. MATERIALS AND METHODS: Thirty patients with STEMI were
      included in the study. During acute primary coronary intervention, patients
      received aspirin (acetylsalicylic acid) and clopidogrel in a loading dose of
      300mg. Clopidogrel was the only antiplatelet therapy used by nine patients (group
      B). Twenty-one patients (group A) received additional abciximab. Blood samples
      were collected and analyzed twice: before and up to 22 hours after administration
      of antiplatelet therapy. The platelet aggregation was established as primary
      platelet-related hemostasis (closure time [CT] assessed using the PFA100 system).
      The absolute number of platelet surface antigens as CD41a, CD42a, CD42b, CD61,
      and CD62P were determined by flow cytometry analysis. RESULTS: The study revealed
      a statistically significant increase in CT induced by adenosine diphosphate and
      adrenaline (epinephrine) +130 seconds (p < 0.0001) and +94 seconds (p < 0.0001),
      respectively, in group A patients post-therapy. While in group B the parameters
      of CT did not change after treatment. In addition, the absolute number of CD41a
      antigens (glycoprotein [GP] IIb/IIIa) increased significantly after treatment in
      group A. No significant changes were observed after treatment in the expression
      of CD62P (P-selectin) antigens in either treatment group. There was a significant
      reduction in the percentage of CD62P-positive platelets in group B after
      antiplatelet therapy. CONCLUSIONS: The absolute number of GP IIb/IIIa receptors
      increases and platelets are not activated up to 12 hours after cessation of
      abciximab therapy. Treatment of STEMI patients undergoing PCI with a loading dose
      of clopidogrel reduces the percentage of active platelets but does not influence
      the CT.

PMID- 18076211
TI  - Estimating the cost effectiveness of ramipril used for specific clinical
      indications: comparing the outcomes in four clinical trials with a common
      economic model.
AB  - BACKGROUND AND OBJECTIVES: Economic analyses of drug therapies are highly
      dependent on the clinical indications for treatment. The cost effectiveness of
      ramipril has been evaluated in numerous studies, usually based on the results of
      one specific clinical trial. We estimated the cost effectiveness of this drug
      across a range of currently accepted therapeutic indications, using a single
      health economic model and adjusted for quality of life, to compare the different
      outcomes observed in four clinical trials. METHODS: The cardiovascular life
      expectancy model, a validated Markov model, was calibrated to accurately forecast
      the results of four trials including AIRE, HOPE, Micro-HOPE, and REIN. We then
      extrapolated these results over the remaining life expectancy of the patients
      enrolled in each study and adjusted for the quality of life associated with the
      observed outcomes. The cost per quality-adjusted life-year (QALY) was then
      calculated from the perspective of the Canadian healthcare system incorporating
      the estimated direct healthcare costs associated with treatments and outcomes.
      RESULTS: After discounting all costs and outcomes 3% annually, the benefits
      associated with ramipril ranged from 0.74 QALYs in the AIRE study to 1.22 QALYs
      in Micro-HOPE. Treatment was estimated to be cost-saving for some patient groups,
      such as those in REIN. The highest cost-effectiveness ratio was observed among
      individuals enrolled in HOPE ($Can20 000 per QALY in 2002). CONCLUSION: Treatment
      with ramipril appears to be economically attractive across a wide range of
      patient groups, including those with increased coronary risk and/or diabetes
      mellitus (HOPE and Micro-HOPE), those with congestive heart failure (AIRE), and
      those with non-diabetic nephropathy (REIN).

PMID- 18076212
TI  - Improving care in resistant hypertension: medication trends and nonpharmacologic
      strategies in a specialty clinic.
AB  - OBJECTIVE: Resistant hypertension is an important clinical problem that is poorly
      studied and not well managed. The objective of this study was to identify factors
      associated with successful treatment of resistant hypertension in a specialty
      clinic. METHODS: This was a retrospective observational study examining the
      medical records of patients seen at a specialty hypertension clinic at the
      University of Rochester, Rochester, New York, USA, in the year 2005. The records
      of 68 patients were reviewed. Those presenting with resistant hypertension
      (defined as BP > or =140/90mm Hg and receiving at least three antihypertensive
      medications, including a diuretic) were identified. Change in medication type and
      dosage, BP reduction, and percentage of patients at Joint National Committee
      (JNC)-7 goal were noted. RESULTS: Twenty-eight patients were included in the
      analysis. Mean age was 62.5 +/- 11.6 years, 54% were women, and mean presenting
      BP was 175.4 +/- 23.5/87.5 +/- 14.6mm Hg. After an average of 6.2 +/- 3.2 visits
      over a mean of 13.9 +/- 13.5 months, mean BP was reduced to 145.3 +/- 27.7/73.9
      +/- 13.6mm Hg (paired t-test: p = 0.001 SBP, p = 0.0001 DBP), and 44.8% of the
      patients were at their JNC-7 goal. Change in the mean number of antihypertensive
      medications was not significantly different between the initial and final clinic
      visits (4.1 +/- 1.2 vs 4.2 +/- 1.0; p = 0.627). Combination pill use increased
      from four patients (14%) at initial visit to 19 (68%) at final visit. Numbers of
      patients treated with diuretics, beta-adrenoceptor antagonists, calcium channel
      antagonists (CCB), and minoxidil increased at the final clinic visit. Significant
      dose-related changes included the up-titration of CCBs to high doses, and the
      initiation of moderate doses of thiazide diuretics; mainly chlorthalidone (67%
      final visit vs 0% at initial visit). CONCLUSIONS: Patients referred to a
      specialty clinic for the control of resistant hypertension achieved significant
      reductions in BP with frequent visits, combination pills, and greater use and
      higher doses of CCBs and thiazide diuretics.

PMID- 18076213
TI  - Colesevelam: a review of its use in hypercholesterolemia.
AB  - Colesevelam hydrochloride (Cholestagel, WelChol is an orally administered, non
      absorbable, polymeric, bile-acid-binding agent with a higher affinity for
      glycocholic acid in vitro and greater capacity for binding bile acids in vivo
      than other bile-acid-binding agents. In randomized controlled trials in patients
      with primary hypercholesterolemia, colesevelam monotherapy reduced mean serum low
      density lipoprotein-cholesterol (LDL-C) levels by 9-19%. In combination with an
      HMG-CoA reductase inhibitor (statin) or fenofibrate, colesevelam induced additive
      reductions in LDL-C 10-16% greater than those achieved by monotherapy with a
      statin (in patients with primary hypercholesterolemia) or fenofibrate (in
      patients with mixed hyperlipidemia). Colesevelam was generally well tolerated,
      with a relatively low incidence of gastrointestinal adverse events and a high
      compliance rate. Thus, colesevelam provides a useful addition to primary therapy
      with statins in the treatment of primary hypercholesterolemia, or fenofibrate in
      the treatment of mixed hyperlipidemia.

PMID- 18076214
TI  - Proton pump inhibitors: do differences in pharmacokinetics translate into
      differences in clinical outcomes?
AB  - Acid-related disorders are common management problems in clinical practice. The
      key to effective management is successful suppression of gastric acid production.
      Proton pump inhibitors (PPIs) are the most potent acid suppressants available and
      are significantly more effective than histamine H(2) receptor antagonists.
      Although PPIs are highly effective as a class, differences in their
      pharmacokinetics, such as bioavailability, elimination half-life and metabolism,
      may translate into differences in clinical outcomes. A new immediate-release
      omeprazole has been introduced, which allows rapid absorption. This has been
      shown to produce significantly better nocturnal gastric acid control than delayed
      release tablets. The bioavailability of rabeprazole on day 1 is greater than with
      other PPIs, and this may translate into faster onset of symptom relief for
      patients with gastro-oesophageal reflux disease. On the other hand, the
      bioavailability of esomeprazole increases 3-fold at day 5, and it has been shown
      that on day 5, esomeprazole provided significantly more effective control of
      gastric acid than other PPIs. The exact clinical significance of these
      observations remains to be determined. There is genetic polymorphism in PPI
      metabolism via cytochrome P450 2C19. In Helicobacter pylori eradication, a
      significantly lower eradication rate was seen in extensive metabolisers with
      omeprazole and lansoprazole but not with rabeprazole. The oesophagitis healing
      rate was lower in extensive metabolisers with lansoprazole but not with
      rabeprazole. The currently available PPIs have short elimination half-lives
      ranging from 1 to 1.5 hours. Tenatoprazole is a new PPI that has a 5- to 7-fold
      longer elimination half-life than current PPIs. It could be potentially more
      useful for the treatment of gastro-esophageal reflux disease and nocturnal acid
      breakthrough than other PPIs.

PMID- 18076215
TI  - Clinical pharmacokinetics and pharmacodynamics of insulin glulisine.
AB  - Insulin glulisine injection [3(B)-Lys, 29(B)-Glu-human insulin] is the newest
      human insulin analogue product for the control of mealtime blood sugar. As with
      insulin aspart and insulin lispro products, the insulin glulisine product
      displays faster absorption and onset of action, with a shorter duration of action
      than that of regular human insulin. The modifications of the amino acid sequence
      at positions 3 and 29 in the B chain of human insulin simultaneously provide
      stability to the molecular structure and render the insulin glulisine molecule
      less likely to self-associate, compared with human insulin, while still allowing
      the formation of dimers at pharmaceutical concentrations. Unlike other insulin
      analogue products, this allows for a viable drug product in the absence of
      hexamer-promoting zinc and, thus, provides immediate availability of insulin
      glulisine molecules at the injection site for absorption. Pharmacokinetic studies
      with insulin glulisine have shown an absorption profile with a peak insulin
      concentration approximately twice that of regular human insulin, which is reached
      in approximately half the time. Dose proportionality in early, maximum and total
      exposure is observed for insulin glulisine over the therapeutic relevant dose
      range up to 0.4 U/kg. The pharmacodynamic profile of insulin glulisine reflects
      the absorption kinetics by demonstrating a greater rate of glucose utilization,
      which is completed earlier and at equipotency on a molar base compared with
      regular human insulin. Dose-proportionality in glucose utilization has been
      established for insulin glulisine in patients with type 1 diabetes mellitus in
      the dose range of 0.075-0.15 U/kg, and a less than dose-proportional increase
      above 0.15 U/kg, indicating saturation of insulin action in general. The rapid
      absorption and action of insulin glulisine show similar low intrasubject
      variability compared with insulin lispro and regular human insulin when given
      repeatedly, and have been confirmed in healthy subjects of different body mass
      indices (BMIs) and ethnic groups, as well as adults and children with type 1 and
      type 2 diabetes. Furthermore, the early insulin exposure and action of insulin
      glulisine were slightly -- but consistently -- greater than those of insulin
      lispro in healthy volunteers across a wide range of BMIs.Meal studies in patients
      with type 1 diabetes show that insulin glulisine provides better postprandial
      blood glucose control than regular human insulin when administered immediately
      pre-meal, and equivalent control when given after the meal. In a study in
      patients with type 2 diabetes, the overall postprandial blood glucose excursions
      were lower with insulin glulisine than with insulin lispro. Therefore, by virtue
      of its primary structure, insulin glulisine demonstrates both low self
      association in solution and stability for a viable insulin product in the absence
      of zinc, thereby maintaining immediate availability for absorption after
      subcutaneous injection. This confers the most rapid onset of glucose-lowering
      activity and adds to the flexibility in postprandial blood glucose control.

PMID- 18076216
TI  - Pharmacokinetics and pharmacodynamics of ceftobiprole, an anti-MRSA cephalosporin
      with broad-spectrum activity.
AB  - Ceftobiprole, a beta-lactam, is the first of a new generation of broad-spectrum
      cephalosporins in late-stage development with activity against methicillin
      resistant Staphylococcus aureus (MRSA) in addition to broad-spectrum bactericidal
      activity against other Gram-positive and Gram-negative pathogens. The prodrug,
      ceftobiprole medocaril, is converted rapidly and almost completely to the active
      drug, ceftobiprole, upon infusion by type A esterases. In humans, ceftobiprole
      binds minimally (16%) to plasma proteins, and binding is independent of the drug
      and protein concentrations. Its steady-state volume of distribution (18.4 L)
      approximates the extracellular fluid volume in humans. Ceftobiprole undergoes
      minimal hepatic metabolism, and the primary metabolite is the beta-lactam ring
      opened hydrolysis product (open-ring metabolite). Systemic exposure of the open
      ring metabolite accounts for 4% of ceftobiprole exposure following single-dose
      administration; approximately 5% of the dose is excreted in the urine as the
      metabolite. Ceftobiprole does not significantly induce or inhibit relevant
      cytochrome P450 enzymes and is neither a substrate nor an inhibitor of P
      glycoprotein. Ceftobiprole is rapidly eliminated, primarily unchanged, by renal
      excretion, with a terminal elimination half-life of 3 hours; the predominant
      mechanism responsible for elimination is glomerular filtration, with
      approximately 89% of the dose being excreted as the prodrug, active drug
      (ceftobiprole) and open-ring metabolite. The pharmacokinetics of ceftobiprole are
      linear following single and multiple infusions of 125-1000 mg. Steady-state drug
      concentrations are attained on the first day of dosing, with no appreciable
      accumulation when administered three times daily (every 8 hours) and twice daily
      (every 12 hours) in subjects with normal renal function. Low intersubject
      variability has been seen across studies. Ceftobiprole exposure is slightly
      higher (~15%) in females than in males; this difference has been attributed to
      bodyweight. However, the pharmacodynamics of ceftobiprole are similar in males
      and females, and dosing adjustments are not required based on gender. In patients
      with moderate to severe renal impairment, systemic clearance of ceftobiprole
      correlated well with creatinine clearance. For these patients, dose adjustments
      for the treatment of infections caused by target pathogens, including MRSA,
      should be based on creatinine clearance. Ceftobiprole is undergoing clinical
      evaluation in phase III trials in patients with complicated skin and skin
      structure infections, patients with nosocomial pneumonia, and community-acquired
      pneumonia in hospitalized patients.

PMID- 18076217
TI  - Predicting oral clearance in humans: how close can we get with allometry?
AB  - BACKGROUND: Oral clearance (CL/F) is an important pharmacokinetic parameter and
      plays an important role in the selection of a safe and tolerable dose for first
      in-human studies. Throughout the pharmaceutical industry, many drugs are
      administered via the oral route; however, there are only a handful of published
      scaling studies for the prediction of oral pharmacokinetic parameters. METHODS:
      We evaluated the predictive performances of four different allometric approaches 
      - simple allometry (SA), the rule of exponents, the unbound CL/F approach, and
      the unbound fraction corrected intercept method (FCIM) -- for the prediction of
      human CL/F and the oral area under the plasma concentration-time curve (AUC).
      Twenty-four compounds developed at Johnson and Johnson Pharmaceutical Research
      and Development, covering a wide range of physicochemical and pharmacokinetic
      properties, were selected. The CL/F was predicted using these approaches, and the
      oral AUC was then estimated using the predicted CL/F. RESULTS: The results of
      this study indicated that the most successful predictions of CL/F and the oral
      AUC were obtained using the unbound CL/F approach in combination with the maximum
      lifespan potential or the brain weight as correction factors based on the rule of
      exponents. We also observed that the unbound CL/F approach gave better
      predictions when the exponent of SA was between 0.5 and 1.2. However, the FCIM
      seemed to be the method of choice when the exponent of SA was <0.50 or >1.2.
      CONCLUSIONS: Overall, we were able to predict CL/F and the oral AUC within 2-fold
      of the observed value for 79% and 83% of the compounds, respectively, by
      selecting the allometric approaches based on the exponents of SA.

PMID- 18076218
TI  - Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor
      dabigatran in healthy elderly subjects.
AB  - OBJECTIVES: To investigate the pharmacokinetic and pharmacodynamic profile of
      dabigatran in healthy elderly subjects; to assess the intra- and interindividual
      variability of dabigatran pharmacokinetics in order to assess possible gender
      differences; and to assess the effect of pantoprazole coadministration on the
      bioavailability of dabigatran. STUDY DESIGN AND SETTING: Open-label, parallel
      group, single-centre study, consisting of a baseline screening visit, 7-day
      treatment period and post-study examination visit. SUBJECTS AND INTERVENTION: 36
      healthy elderly subjects (aged > or =65 years) with a body mass index of 18.5
      29.9 kg/m(2). Subjects were randomized to receive dabigatran etexilate either
      with or without coadministration of pantoprazole. Dabigatran etexilate was
      administered as capsules at 150 mg twice daily over 6 days and once on the
      morning of day 7. Pantoprazole was administered at 40 mg twice daily, starting 2
      days prior to dabigatran etexilate administration and ending on the morning of
      day 7. MAIN OUTCOME MEASURES: The primary pharmacokinetic measurements included
      the area under the plasma concentration-time curve at steady state (AUC(ss)),
      maximum (C(max,ss)) and minimum (C(min,ss)) plasma concentrations at steady
      state, terminal half-life (t((1/2))), time to reach C(max,ss) and renal clearance
      of dabigatran. The secondary pharmacokinetic parameters included the mean
      residence time, total oral clearance and volume of distribution. The
      pharmacodynamic parameters measured were the blood coagulation parameters ecarin
      clotting time (ECT) and activated partial thromboplastin time (aPTT). RESULTS:
      With twice-daily administration of dabigatran etexilate, plasma concentrations of
      dabigatran reached steady state within 2-3 days, which is consistent with a
      t((1/2)) of 12-14 hours. The mean (SD) peak plasma concentrations on day 4 of
      treatment in male and female elderly subjects were 256 ng/mL (21.8) and 255 ng/mL
      (84.0), respectively. The peak plasma concentrations were reached after a median
      of 3 hours (range 2.0-4.0 hours). Coadministration with pantoprazole decreased
      the average bioavailability of dabigatran (the AUC(ss)) by 24% (day 4; 90% CI
      7.4, 37.8) and 20% (day 7; 90% CI 5.2, 33.3). Intra- and interindividual
      pharmacokinetic variability in the overall population was low (<30% coefficient
      of variation), indicating that dabigatran has a predictable pharmacokinetic
      profile. Prolongation of the ECT and aPTT correlated with, and paralleled, the
      plasma concentration-time profile of dabigatran, which demonstrates a rapid onset
      of action without a time delay, and also illustrates the direct mode of action of
      the drug on thrombin in plasma. The ECT increased in direct proportion to the
      plasma concentration, and the aPTT displayed a linear relationship with the
      square root of the plasma concentration. The mean AUC(ss) was 3-19% higher in
      female subjects than in male subjects, which was likely due to gender differences
      in creatinine clearance. The safety profile of dabigatran was good, with and
      without pantoprazole coadministration. CONCLUSIONS: Dabigatran demonstrated
      reproducible and predictable pharmacokinetic and pharmacodynamic characteristics,
      together with a good safety profile, when administered to healthy elderly
      subjects. Minor gender differences were not considered clinically relevant. The
      effects of pantoprazole coadministration on the bioavailability of dabigatran
      were considered acceptable, and dose adjustment is not considered necessary.

PMID- 18076221
TI  - Effect of torso rotational strength on angular hip, angular shoulder, and linear
      bat velocities of high school baseball players.
AB  - This investigation examined the effect of torso rotational strength on angular
      hip (AHV), angular shoulder (ASV), linear bat-end (BEV), and hand velocities (HV)
      and 3 repetition maximum (RM) torso rotational and sequential hip-torso-arm
      rotational strength (medicine ball hitter's throw) in high school baseball
      players (age 15.4 +/- 1.2 y). Participants were randomly assigned to 1 of 2
      training groups. Group 1 (n = 24) and group 2 (n = 25) both performed a stepwise
      periodized resistance exercise program and took 100 swings a day, 3 days a week,
      for 12 weeks with their normal game bat. Group 2 performed additional rotational
      and full-body medicine ball exercises 3 days a week for 12 weeks. A 3RM parallel
      squat and bench press were measured at 0 and after 4, 8, and 12 weeks.
      Participants were pre- and posttested for 3RM dominant and nondominant torso
      rotational strength and medicine ball hitter's throw. Angular hip velocities,
      ASV, BEV, and HV were recorded pre- and posttraining by a motion capture system
      that identified and digitally processed reflective markers attached to each
      participant's bat and body. Groups 1 and 2 increased (p < or = 0.05) BEV (3.6 and
      6.4%), HV (2.6 and 3.6%), 3RM dominant (10.5 and 17.1%) and nondominant (10.2 and
      18.3%) torso rotational strength, and medicine ball hitter's throw (3.0 and
      10.6%) after 12 weeks. Group 2 increased AHV (6.8%) and ASV (8.8%). Group 2
      showed greater improvements in BEV, AHV, ASV, 3RM dominant and nondominant torso
      rotational strength, and medicine ball hitter's throw than group 1. Groups 1 and
      2 increased predicted 1RM parallel squat (29.7 and 26.7%) and bench press (17.2
      and 16.7%) strength after 12 weeks. These data indicate that performing
      additional rotational medicine ball exercises 2 days a week for 12 weeks
      statistically improves baseball performance variables.

PMID- 18076222
TI  - Effect of whole body vibration training on lower limb performance in selected
      high-level ballet students.
AB  - The aim of this study was to examine the effects of 8 weeks of whole body
      vibration (WBV) training on vertical jump ability (CMJ) and knee-extensor
      performance at selected external loads (50, 70, and 100 kg; leg-press exercise)
      in elite ballerinas. Twenty-two (age, 21.25 +/- 1.5 years) full-time ballerinas
      were assigned randomly to the experimental (E, n = 11) and control (C, n = 11)
      groups. The experimental group was submitted to WBV training 3 times per week
      before ballet practice. During the training period, the E and C groups undertook
      the same amount of ballet practice. Posttraining CMJ performance significantly
      increased in E group (6.3 +/- 3.8%, p < 0.001). Furthermore, E group showed
      significant (p < 0.05-0.001) posttraining average leg-press power and velocity
      improvements at all the external loads considered. Consequently, the force
      velocity and power-velocity relationship shifted to the right after WBV training
      in the E group. The results of the present study show that WBV training is an
      effective short-term training methodology for inducing improvements in knee
      extensor explosiveness in elite ballerinas.

PMID- 18076219
TI  - Interaction profile of armodafinil with medications metabolized by cytochrome
      P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects.
AB  - BACKGROUND AND OBJECTIVE: Armodafinil, a wakefulness-promoting agent, is the pure
      R-enantiomer of racemic modafinil. The objective of this article is to summarize
      the results of three clinical drug-interaction studies assessing the potential
      for drug interactions of armodafinil with agents metabolized by cytochrome P450
      (CYP) enzymes 1A2, 3A4 and 2C19. Study 1 evaluated the potential for armodafinil
      to induce the activity of CYP1A2 using oral caffeine as the probe substrate.
      Study 2 evaluated the potential for armodafinil to induce gastrointestinal and
      hepatic CYP3A4 activity using intravenous and oral midazolam as the probe
      substrate. Study 3 evaluated the potential for armodafinil to inhibit the
      activity of CYP2C19 using oral omeprazole as the probe substrate. METHODS:
      Healthy men and nonpregnant women aged 18-45 years with a body mass index of
      </=30 kg/m(2) each participated in one of three open-label studies. Studies 1 and
      2 were sequential design studies in which caffeine (oral 200 mg) or midazolam (2
      mg intravenously followed by 5 mg orally) was administered before initiation of
      oral armodafinil administration and again after at least 22 days of oral
      armodafinil administration at 250 mg/day. Study 3 was a two-way crossover study
      in CYP2C19 extensive metabolizers to whom omeprazole (oral 40 mg) was
      administered alone or with oral administration of armodafinil 400 mg 2 hours
      before the omeprazole dose. Pharmacokinetic samples were obtained for caffeine,
      midazolam and omeprazole for up to 48 hours postdose. The primary pharmacokinetic
      parameters included the area under the plasma concentration-time curve from time
      zero to infinity (AUC(infinity)) and the maximum observed drug plasma
      concentration (C(max)). Safety and tolerability were also assessed. RESULTS: A
      total of 77 healthy subjects participated in the three studies (study 1, n = 29;
      study 2, n = 24; study 3, n = 24). Prolonged armodafinil administration had no
      effect on the C(max) or the AUC of oral caffeine compared with administration of
      caffeine alone. However, prolonged administration of armodafinil reduced the AUC
      of midazolam after intravenous and oral doses by approximately 17% and 32%,
      respectively, and decreased the C(max) of oral midazolam by approximately 19%
      compared with administration of midazolam alone. Armodafinil coadministration
      increased the AUC of oral omeprazole by approximately 38% compared with
      administration of omeprazole alone. Armodafinil alone or in combination with each
      of the three probe substrates was well tolerated, with headache and dizziness
      being the most commonly reported adverse events. CONCLUSIONS: Armodafinil did not
      induce CYP1A2 but was a moderate inducer of CYP3A4 and a moderate inhibitor of
      CYP2C19 in healthy subjects. Armodafinil was generally well tolerated when
      administered with caffeine, midazolam or omeprazole. Dosage adjustments may be
      required for drugs that are substrates of CYP3A4 (e.g. ciclosporin, triazolam)
      and CYP2C19 enzymes (e.g. diazepam, phenytoin) when administered with
      armodafinil.

PMID- 18076223
TI  - Pre-exercise stretching does not impact upon running economy.
AB  - Pre-exercise stretching has been widely reported to reduce performance in tasks
      requiring maximal or near-maximal force or torque. The purpose of this study was
      to compare the effects of 3 different pre-exercise stretching routines on running
      economy. Seven competitive male middle and long-distance runners (mean +/- SD)
      age: 32.5 +/- 7.7 years; height: 175.0 +/- 8.8 cm; mass: 67.8 +/- 8.6 kg; V(.
      )O2max: 66.8 +/- 7.0 ml x kg(-1) x min(-1)) volunteered to participate in this
      study. Each participant completed 4 different pre-exercise conditions: (a) a
      control condition, (b) static stretching, (c) progressive static stretching, and
      (d) dynamic stretching. Each stretching routine consisted of 2 x 30-second
      stretches for each of 5 exercises. Dependent variables measured were sit and
      reach test before and after each pre-exercise routine, running economy (ml x kg(
      1) x km(-1)), and steady-state oxygen uptake (ml x kg(-1) x min(-1)), which were
      measured during the final 3 minutes of a 10-minute run below lactate threshold.
      All 3 stretching routines resulted in an increase in the range of movement (p =
      0.008). There was no change in either running economy (p = 0.915) or steady-state
      V(.-)O2 (p = 0.943). The lack of change in running economy was most likely
      because it was assessed after a period of submaximal running, which may have
      masked any effects from the stretching protocols. Previously reported reductions
      in performance have been attributed to reduced motor unit activation, presumably
      IIX. In this study, these motor units were likely not to have been recruited;
      this may explain the unimpaired performance. This study suggests that pre
      exercise stretching has no impact upon running economy or submaximal exercise
      oxygen cost.

PMID- 18076224
TI  - Early phase strength development: a four-week training comparison of different
      programs.
AB  - The purpose of this study was to explore the effects of various exercise
      sequences in the early weeks of a strength training program. Forty-two untrained
      men were randomly assigned to one of 4 training regimens, which were
      differentiated by the order in which the exercises were performed, and trained 3
      days per week for 4 weeks. Three regimens were multiple-set protocols
      (alternating, blocked, and semiblocked), and the fourth was a single-set
      protocol. The exercises were arm curls, lateral raises, and triceps extensions.
      Results showed that the blocked group improved significantly more on the arm curl
      exercise than the single-set group. No other group comparisons were significant.
      This finding indicates that a blocked multiple-set regimen is superior to a
      single-set regimen for certain upper-body exercises in the early stages of
      strength training.

PMID- 18076225
TI  - The development of trunk muscles in male wrestlers assessed by magnetic resonance
      imaging.
AB  - The purpose of this study was to compare the development of trunk musculature
      among Elite, Sub-elite, and Elite junior wrestlers. The performance level of
      these groups, ordered highest to lowest, is as follows: Elite (n = 20), Sub-elite
      (n = 25), and Elite junior (n = 39). A magnetic resonance imaging device was used
      to measure the cross-sectional area (CSA) of the trunk muscles. The whole trunk
      muscle cross-sectional area (t-MCSA) of the Elite group was significantly larger
      than that of the Elite junior group (p < 0.05). The rectus abdominis muscle CSA
      of the Elite group was significantly larger than that of the Elite junior group
      (p < 0.01). The psoas major muscle CSA of the Elite group was significantly
      larger than that of the Elite junior group (p < 0.05). There were no significant
      differences in the CSA of any of the trunk muscles between the Elite and Sub
      elite groups. In conclusion, compared with Elite junior wrestlers, it is
      conceivable that a greater CSA of trunk flexors of Elite wrestlers is one factor
      which supports increased performance.

PMID- 18076226
TI  - Power performance of soccer referees before, during, and after official matches.
AB  - The study aimed at verifying the effect of soccer refereeing on power
      performances, evaluated by means of countermovement (CMJ) and bounce (BJ) jumps.
      Ten soccer referees (age 23 +/- 3 years; V(.-)O2max 51.8 +/- 3.2 ml x kg(-1) x
      min(-1)) participated in this study. The physical load of refereeing was
      evaluated by means of subject's heart rate (HR), motor activities recorded during
      the match, and blood lactate measured at the end of the 2 halves. Analysis of
      variance and chi-square tested the differences between halves (p < 0.05). During
      the first half, the occurrence of subject's HR >85%HRmax was 62 +/- 31%, and it
      significantly (p < 0.05) decreased to 45 +/- 24% during the second half. Referees
      spent 41 +/- 5% running, 44 +/- 6% walking, and 15 +/- 5% inactivity, with no
      significant differences between halves. Blood lactate was significantly different
      only between warm-up (2.0 +/- 0.4 mM) and first half (4.7 +/- 2.9 mM). No
      significant difference emerged for CMJ and BJ after the 2 halves, demonstrating
      that young referees with acceptable fitness levels are able to maintain their all
      out capabilities during the whole match.

PMID- 18076227
TI  - Effective speed and agility conditioning methodology for random intermittent
      dynamic type sports.
AB  - Different coaching methods are often used to improve performance. This study
      compared the effectiveness of 2 methodologies for speed and agility conditioning
      for random, intermittent, and dynamic activity sports (e.g., soccer, tennis,
      hockey, basketball, rugby, and netball) and the necessity for specialized
      coaching equipment. Two groups were delivered either a programmed method (PC) or
      a random method (RC) of conditioning with a third group receiving no conditioning
      (NC). PC participants used the speed, agility, quickness (SAQ) conditioning
      method, and RC participants played supervised small-sided soccer games. PC was
      also subdivided into 2 groups where participants either used specialized SAQ
      equipment or no equipment. A total of 46 (25 males and 21 females) untrained
      participants received (mean +/- SD) 12.2 +/- 2.1 hours of physical conditioning
      over 6 weeks between a battery of speed and agility parameter field tests. Two
      way analysis of variance results indicated that both conditioning groups showed a
      significant decrease in body mass and body mass index, although PC achieved
      significantly greater improvements on acceleration, deceleration, leg power,
      dynamic balance, and the overall summation of % increases when compared to RC and
      NC (p < 0.05). PC in the form of SAQ exercises appears to be a superior method
      for improving speed and agility parameters; however, this study found that
      specialized SAQ equipment was not a requirement to observe significant
      improvements. Further research is required to establish whether these benefits
      transfer to sport-specific tasks as well as to the underlying mechanisms
      resulting in improved performance.

PMID- 18076228
TI  - Reproducibility of power production during sprint arm ergometry.
AB  - Sprint tests are frequently used to evaluate between-subject differences and can
      provide a valuable insight into performance capacity. The present study
      determined the reproducibility of peak and mean power output during upper-body
      sprints. After familiarization 25 men (mean [+/- SD] age 29 [6] years, body mass
      82.8 [12.7] kg and height 1.76 [0.05] m) completed 2 20-second upper-body sprint
      tests using an adapted cycle ergometer. Mean (+/- SD) values of all power
      (uncorrected and corrected) measurements achieved during the 2 tests were checked
      for systematic bias using separate paired t-tests. Test-retest reproducibility
      was examined using coefficients of variation and single-measure intraclass
      correlation coefficients, as well as an assessment of the typical (random) error
      and the 95% limits of agreement. The value of corrected peak power (628 [167] W)
      was higher (p < 0.05) compared with the uncorrected value (509 [109] W). Values
      of corrected (465 [95] W) and uncorrected (444 [87] W) mean power were similar (p
      > 0.05). The mean bias value for all power parameters equated to less than +/-1%
      of the absolute values of power measured. Intraclass correlation coefficients for
      all data sets ranged from 0.97 to 0.98. Coefficients of variation for uncorrected
      and corrected values of peak power were 2.8 and 4.5%, while corresponding values
      for mean power were 2.9 and 3.2%, respectively. The reproducibility of all power
      indices was below 5%. The results of this study indicate that both uncorrected
      and corrected measurements of peak power output and mean power output can be used
      to assess performance during sprint arm ergometry.

PMID- 18076229
TI  - Effect of pre-performance lower-limb massage on thirty-meter sprint running.
AB  - Massage is a commonly utilized therapy within sports, frequently intended as an
      ergogenic aid prior to performance. However, evidence as to the efficacy of
      massage in this respect is lacking, and massage may in some instances reduce
      force production. The aim of this study was to investigate the effect of massage
      on subsequent 30-m sprint running performance. Male university level repeat
      sprint sports players volunteered for the study (n = 37). After each of 3
      treatment conditions, subjects completed a standardized warm-up followed by three
      30-m sprint trials in a counterbalanced crossover design. Treatment conditions
      were 15 minutes of lower-limb massage (M), 15 minutes of placebo ultrasound (PU),
      and rest (R). Thirty-meter sprint times were recorded (including 10-m split
      times) for the 3 trials under each condition. Best times at 10 m (M: 1.85 +/-
      0.09 seconds, PU: 1.84 +/- 0.11 seconds, R: 1.83 +/- 0.10 seconds) and 30 m (M:
      4.41 +/- 0.27 seconds, PU: 4.39 +/- 0.28 seconds, R: 4.39 +/- 0.28 seconds) were
      not significantly different (p > 0.05). There was no significant treatment,
      trial, or interaction effect for 10- or 30-m sprint times (p > 0.05). No
      difference was seen in the location of subjects' best times across the 3 trials
      (p > 0.05). Relative to placebo or control, the results of this study showed that
      a controlled 15-minute lower-limb massage administered prior to warm-up had no
      significant effect on subsequent 30-m sprint performance. Massage remains
      indicated prior to performance where other benefits, such as reduced muscle spasm
      and psychological stress, might be served to the athlete.

PMID- 18076230
TI  - Effects of saddle height on anaerobic power production in cycling.
AB  - In competitive cycling, setting the proper saddle height is important for both
      performance and injury prevention. This is also true for ergometer use in a
      laboratory. The cycling literature recommends using a 25 to 35 degrees knee angle
      to set saddle height for injury prevention and recommends using 109% of inseam
      length for optimal performance. Prior research has demonstrated that these 2
      methods do not produce similar saddle heights. The purpose of this study was to
      determine if there is a difference in performance between these 2 methods.
      Trained cyclists (n = 9) and noncyclists (n = 18) participated in this study.
      Anaerobic power production was compared using a 30s Wingate protocol at a saddle
      height of 109% of inseam and at 25 and 35 degrees knee angles. Saddle height set
      using 109% of inseam fell outside the recommended 25 to 35 degrees knee angle 63%
      of the time. There were no significant differences (p > 0.05) for peak power and
      mean power in either group between saddle heights. The data when using 109% to
      set saddle height were then divided into those that fell within the recommended
      25 to 35 degrees knee angle and those that fell outside. A 25 degrees knee angle
      produced a significantly higher mean power compared with 109% in those that fell
      outside the recommended range. An increase in power, at a 25 degrees angle, can
      be extrapolated to increased performance. There was no difference in performance
      detected in those individuals who fell within the recommended range. For this
      reason it is recommended that saddle height for cycles and ergometers be set
      using a 25 to 35 degrees knee angle for both trained and untrained cyclists for
      both injury prevention and increased performance.

PMID- 18076231
TI  - Trunk muscle activation during dynamic weight-training exercises and isometric
      instability activities.
AB  - The purpose of this study was to examine the extent of activation in various
      trunk muscles during dynamic weight-training and isometric instability exercises.
      Sixteen subjects performed squats and deadlifts with 80% 1 repetition maximum
      (1RM), as well as with body weight as resistance and 2 unstable calisthenic-type
      exercises (superman and sidebridge). Electromyographic (EMG) activity was
      measured from the lower abdominals (LA), external obliques (EO), upper lumbar
      erector spinae (ULES), and lumbar-sacral erector spinae (LSES) muscle groups.
      Results indicated that the LSES EMG activity during the 80% 1RM squat
      significantly exceeded 80% 1RM deadlift LSES EMG activity by 34.5%. The LSES EMG
      activity of the 80% 1RM squat also exceeded the body weight squat, deadlift,
      superman, and sidebridge by 56, 56.6, 65.5, and 53.1%, respectively. The 80% 1RM
      deadlift ULES EMG activity significantly exceeded the 80% 1RM squat exercise by
      12.9%. In addition, the 80% 1RM deadlift ULES EMG activity also exceeded the body
      weight squat, deadlift, superman, and sidebridge exercises by 66.7, 65.5, 69.3,
      and 68.6%, respectively. There were no significant changes in EO or LA activity.
      Therefore, the augmented activity of the LSES and ULES during 80% 1RM squat and
      deadlift resistance exercises exceeded the activation levels achieved with the
      same exercises performed with body weight and selected instability exercises.
      Individuals performing upright, resisted, dynamic exercises can achieve high
      trunk muscle activation and thus may not need to add instability device exercises
      to augment core stability training.

PMID- 18076232
TI  - Relation between maximal aerobic power and the ability to repeat sprints in young
      basketball players.
AB  - The aim of this study was to examine the effects of maximal aerobic power (V(.
      )O2max peak) level on the ability to repeat sprints (calculated as performance
      decrement and total sprinting time) in young basketball players. Subjects were 18
      junior, well-trained basketball players (age, 16.8 +/- 1.2 years; height, 181.3
      +/- 5.7 cm; body mass, 73 +/- 10 kg; V(.-)O2max peak, 59.6 +/- 6.9 ml x kg(-1) x
      min(-1)). Match analysis and time-motion analysis of competitive basketball games
      was used to devise a basketball-specific repeated-sprint ability protocol
      consisting of ten 15-m shuttle run sprints with 30 s of passive recovery. Pre,
      post, and post plus 3-minute blood lactate concentrations were 2.5 +/- 0.7, 13.6
      +/- 3.1, and 14.2 +/- 3.5 mmol x L(-1), respectively. The mean fatigue index (FI)
      value was 3.4 +/- 2.3% (range, 1.1-9.1%). No significant correlations were found
      between V(.-)O2max peak and either FI or total sprint time. A negative
      correlation (r = -0.75, p = 0.01) was found between first-sprint time and FI. The
      results of this study showed that V(.-)O2max peak is not a predictor of repeated
      sprint ability in young basketball players. The high blood lactate concentrations
      found at the end of the repeated-sprint ability protocol suggest its use for
      building lactate tolerance in conditioned basketball players.

PMID- 18076233
TI  - The relationship between preseason range of motion and muscle strain injury in
      elite soccer players.
AB  - The purpose of the study was to determine the influence of preseason lower
      extremity range of motion (ROM) on the risk of muscle strain injury during a
      competitive season for elite soccer players. Thirty-six elite male soccer players
      (age, 25.6 +/- 4.7 years) had maximum static ROM for 6 movements of the lower
      extremity measured prior to the 2003-2004 English Premier League season. Player
      age, body size, dominant limb, and playing position were documented also. All
      lower-extremity muscle strain injuries were recorded prospectively during the
      competitive season, as was the total amount of time spent in training and games
      for each player. Soccer players sustaining a muscle strain injury in the hip
      flexors or knee flexors had lower preseason ROM (p < 0.05) in these muscle groups
      compared with uninjured players. Similar trends were observed for the remaining
      muscle groups, but all failed to reach statistical significance (p > 0.05). Most
      significantly, soccer players with lower preseason ROM in the hip flexors and
      knee flexors had a statistically higher risk for a muscle strain injury to these
      muscle groups during a competitive season. Age, body size, limb dominance, and
      playing position were not significant intrinsic risk factors for the development
      of muscle strain injuries. Screening of flexibility for soccer players should be
      conducted during preseason, and flexibility training should be prescribed to
      players with reduced ROM to lower the risk of developing a muscle strain injury.

PMID- 18076234
TI  - A comparison of periodization models during nine weeks with equated volume and
      intensity for strength.
AB  - The purpose of the present investigation was to determine if significant
      differences exist among 3 different periodization programs in eliciting changes
      in strength. Twenty-eight recreationally trained college-aged volunteers (mean +/
      SD; 22.29 +/- 3.98) of both genders were tested for bench press, leg press, body
      fat percentage, chest circumference, and thigh circumference during initial
      testing. After initial testing, subjects were randomly assigned to 1 of 3
      training groups: (a) linear periodization (n = 9), (b) daily undulating
      periodization (n = 10), or (c) weekly undulating periodization (n = 9). The
      training regimen for each group consisted of a 9-week, 3-day-per-week program.
      Training loads were assigned as heavy (90%, 4 repetition maximum [4RM]), medium
      (85%, 6RM), or light (80%, 8RM) for bench press and leg press exercises. Subjects
      were familiarized with the CR-10 rated perceived exertion scale and instructed to
      achieve an 8 or 9 on the final repetition of each set for all other exercises.
      Subjects were then retested after 4 weeks of training. Training loads were then
      adjusted according to the new 1RM. Subjects were then retested after 5 more weeks
      of exercise. For all subjects, significant (p < 0.05) increases in bench press
      and leg press strength were demonstrated at all time points (T1-T3). No
      significant differences (p > 0.05) were observed between groups for bench press,
      leg press, body fat percentage, chest circumference, or thigh circumference at
      all time points. These results indicate that no separation based on periodization
      model is seen in early-phase training.

PMID- 18076235
TI  - A kinetic and electromyographic comparison of the standing cable press and bench
      press.
AB  - This study compared the standing cable press (SCP) and the traditional bench
      press (BP) to better understand the biomechanical limitations of pushing from a
      standing position together with the activation amplitudes of trunk and shoulder
      muscles. A static biomechanical model (4D Watbak) was used to assess the forces
      that can be pushed with 2 arms in a standing position. Then, 14 recreationally
      trained men performed 1 repetition maximum (1RM) BP and 1RM single-arm SP
      exercises while superficial electromyography (EMG) of various shoulder and torso
      muscles was measured. The 1RM BP performance resulted in an average load (74.2 +/
      17.6 kg) significantly higher than 1RM single-arm SP (26.0 +/- 4.4 kg). In
      addition, the model predicted that pushing forces from a standing position under
      ideal mechanical conditions are limited to 40.8% of the subject's body weight.
      For the 1RM BP, anterior deltoid and pectoralis major were more activated than
      most of the trunk muscles. In contrast, for the 1RM single-arm SP, the left
      internal oblique and left latissimus dorsi activities were similar to those of
      the anterior deltoid and pectoralis major. The EMG amplitudes of pectoralis major
      and the erector muscles were larger for 1RM BP. Conversely, the activation levels
      of left abdominal muscles and left latissimus dorsi were higher for 1RM right-arm
      SP. The BP emphasizes the activation of the shoulder and chest muscles and
      challenges the capability to develop great shoulder torques. The SCP performance
      also relies on the strength of shoulder and chest musculature; however, it is
      whole-body stability and equilibrium together with joint stability that present
      the major limitation in force generation. Our EMG findings show that SCP
      performance is limited by the activation and neuromuscular coordination of torso
      muscles, not maximal muscle activation of the chest and shoulder muscles. This
      has implications for the utility of these exercise approaches to achieve
      different training goals.

PMID- 18076236
TI  - Comparison of a kayaking ergometer protocol with an arm crank protocol for
      evaluating peak oxygen consumption.
AB  - The purpose of this study was to compare a kayak ergometer protocol with an arm
      crank protocol for determining peak oxygen consumption (V(.-)O2). On separate
      days in random order, 10 men and 5 women (16-24 years old) with kayaking
      experience completed the kayak ergometer protocol and a standardized arm crank
      protocol. The kayak protocol began at 70 strokes per minute and increased by 10
      strokes per minute every 2 minutes until volitional fatigue. The arm crank
      protocol consisted of a crank rate of 70 revolutions per minute, initial loading
      of 35 W and subsequent increases of 35 W every 2 minutes until volitional
      fatigue. The results showed a significant difference (p < 0.01) between the kayak
      ergometer and the arm crank protocols for relative peak V(.-)O2 (47.5 +/- 3.9 ml
      x kg(-1) x min(-1) vs. 44.2 +/- 6.2 ml x kg(-1) x min(-1)) and absolute peak V(.
      )O2 (3.38 L x min(-1) +/- 0.53 vs. 3.14 +/- 0.64 L x min(-1)). The correlation
      between kayak and arm crank protocol was 0.79 and 0.90, for relative and absolute
      V(.-)O2 peak, respectively (both p < 0.01). The higher peak V(.-)O2 on the kayak
      ergometer may be due to the greater muscle mass involved compared to the arm
      crank ergometer. The kayak ergometer protocol may therefore be more specific to
      the sport of kayaking than an arm crank protocol.

PMID- 18076237
TI  - Acute effect of two aerobic exercise modes on maximum strength and strength
      endurance.
AB  - The purpose of this study was to evaluate the effects of 2 modes of aerobic
      exercise (continuous or intermittent) on maximum strength (1 repetition maximum,
      1RM) and strength endurance (maximum repetitions at 80% of 1RM) for lower- and
      upper-body exercises to test the acute hypothesis in concurrent training (CT)
      interference. Eight physically active men (age: 26.9 +/- 4.2 years; body mass:
      82.1 +/- 7.5 kg; height: 178.9 +/- 6.0 cm) were submitted to: (a) a graded
      exercise test to determine V(.-)O2max (39.26 +/- 6.95 ml x kg(-1) x min(-1)) and
      anaerobic threshold velocity (3.5 mmol x L(-1)) (9.3 +/- 1.27 km x h(-1)); (b)
      strength tests in a rested state (control); and (c) 4 experimental sessions, at
      least 7 days apart. The experimental sessions consisted of a 5-kilometer run on a
      treadmill continuously (90% of the anaerobic threshold velocity) or
      intermittently (1:1 minute at V(.-)O2max). Ten minutes after the aerobic
      exercise, either a maximum strength or a strength endurance test was performed
      (leg press and bench press exercises). The order of aerobic and strength
      exercises followed a William's square distribution to avoid carryover effects.
      Results showed that only the intermittent aerobic exercise produced an acute
      interference effect on leg strength endurance, decreasing significantly (p <
      0.05) the number of repetitions from 10.8 +/- 2.5 to 8.1 +/- 2.2. Maximum
      strength was not affected by the aerobic exercise mode. In conclusion, the acute
      interference hypothesis in concurrent training seems to occur when both aerobic
      and strength exercises produce significant peripheral fatigue in the same muscle
      group.

PMID- 18076238
TI  - Acute effects of heavy- and light-load squat exercise on the kinetic measures of
      vertical jumping.
AB  - This study examined the acute performance enhancing effects of a single light
      load, high-velocity or heavy-load, low-velocity squat intervention set (SIS) on
      stimulating activity-dependent postactivation potentiation and thereby increasing
      vertical jumping performance. Jump performance was assessed using 4 dependent
      variables: net impulse, time of ground contact, and normalized peak and
      normalized minimum vertical ground reaction force. Resistance-trained subjects (n
      = 30) attended 3 independent sessions separated by 3 to 7 days. The first session
      served for familiarization and to determine each subject's 1 repetition maximum
      (1RM) in the squat. In the 2 testing sessions, subjects performed 2
      countermovement jump (CMJ) sets, followed by a single SIS and then a final CMJ
      set. A CMJ set consisted of 3 maximal effort jumps. The testing sessions were
      identical except for SIS intensity, which was 40% of 1RM for 1 session and 80% of
      1RM for the other. The order of the 2 testing sessions was counterbalanced within
      subjects. The 4 dependent variables were reduced for every jump. No significant
      changes were observed from pre- to post-testing in either SIS condition, nor were
      there any differences between the heavy and light SIS loading condition. Reasons
      for the lack of performance enhancement can be attributed to postactivation
      potentiation stimulated by the SIS being insufficient in magnitude or dissipating
      before post-testing. This may have been due to a submaximal workload of 50%
      during the SIS, insufficient movement pattern specificity between the squat
      exercise and a CMJ, or rest intervals of excess duration. A single SIS provides
      no benefit to a warm-up protocol under the current conditions.

PMID- 18076239
TI  - Athletes' use of exercise imagery during weight training.
AB  - Imagery is a cognitive process during which people use their minds to create (or
      recreate) experiences that are similar to real-life situations. This study
      examined how college athletes used imagery during weight training. Subjects were
      295 Division I (n = 163) and Division II (n = 132) college student athletes (men:
      n = 138, women: n = 157) who participated in a weight training program as a
      requirement of their sport. They completed a slightly modified version of the
      "Weight Lifting Imagery Questionnaire." Results showed that appearance imagery
      (i.e., images related to the attainment of a fit-looking body) was used and
      considered the most effective followed by technique imagery (i.e., images related
      to performing the skill and techniques correctly with good form) and energy
      imagery (i.e., images related to getting "psyched up" or feeling energized).
      Other variables that effected imagery use were gender, age, time of season, and
      levels of motivation. In addition, gender, previous imagery training, and level
      of motivation had an effect on the perceptions of imagery effectiveness.
      Confidence in the ability to image was associated with both imagery use and
      effectiveness, and imagery use and effectiveness were associated with confidence
      in the weight room. The findings support previous research in exercise imagery
      that appearance imagery is most used followed by technique and energy imagery and
      extend them in such a way that strength coaches have practical advice on how to
      use imagery in a positive way with their athletes. Suggestions about how strength
      coaches can use imagery with their clients are provided.

PMID- 18076240
TI  - Predicting strength in high school women athletes.
AB  - The purpose of this study was to investigate the hypothesis that a repetitions-to
      maximum test is a predicator of a 1 repetition maximum (1RM) performance for
      evaluating upper and lower body strength in women high school athletes. Fifty
      seven high school athletes ages 14-18 participated in this study. All of the
      participants completed a 1RM bench (1RMBP) and leg press (1RMLP) test, as well as
      leg press repetitions-to-fatigue (91 kg; LPRTF91) and bench press repetitions-to
      fatigue (27 kg; BPRTF27) tests. A Pearson product correlation and regression
      analysis was used to determine relationships between 1RM strength and the
      repetitions-to-fatigue for upper and lower body strength. On the basis of the
      data analysis, it was concluded that BPRTF27 had a high correlation with 1RMBP
      strength (r = 0.802) and LPRTF91 had a correlation with 1RMLP strength (r =
      0.793), indicating that these test measures were viable alternatives to 1RM
      testing for strength assessment. A regression analysis further confirmed that
      BPRTF27 was a significant variables in developing the model 1RMBP = 28.88 +
      (0.68)BPRTF27 for predicting upper body strength (p < 0.001). Similar results
      occurred 1RMLP = 106.3 + (2.4)LPRTF91 in developing the lower body model (p <
      0.001). From data analysis, it was concluded that repetitions-to-fatigue testing
      can be used to evaluate upper and lower body strength in women high school
      athletes.

PMID- 18076241
TI  - Physiological adaptations to head-out aquatic exercises with different levels of
      body immersion.
AB  - The purpose of this study was to compare the physiological adaptations to basic
      head-out aquatic exercises with different levels of body immersion. Sixteen young
      and clinically healthy subjects (9 women and 7 men) volunteered to participate in
      this study. Each subject performed 3 repetitions (on land, immersed to the hip,
      and immersed to the breast) of the aquatic exercise "rocking horse" for 6
      minutes. The rating of perceived effort (RPE), the maximal heart rate achieved
      during the exercitation (HRmax), the percentage of the maximal theoretical heart
      rate estimated (%HRmax), the peak of oxygen uptake during the exercise (V(.
      )O2peak), and the energy expenditure (EE) were evaluated. The RPE was
      significantly higher when exercising immersed to the hip than on land (p < 0.01)
      and immersed to the breast (p = 0.03). The HRmax and %HRmax were significantly
      lower when exercising with immersion to the breast than on land (p < 0.01) and
      with immersion to the hip (p < 0.01). The V(.-)O2peak was significantly different
      between all conditions. The lower mean value was verified when exercising
      immersed to the breast, followed by immersion to the hip and on land. The EE was
      significantly higher when performing aquatic exercises on land than when immersed
      to the hip (p = 0.02) and the breast (p < 0.01). So, physiological responses when
      exercising immersed to the hip are higher than when immersed to the breast. The
      physiological responses when exercising on land are higher than when exercising
      with immersion to the hip and to the breast.

PMID- 18076242
TI  - Relationship between physical fitness and playing ability in rugby league
      players.
AB  - This study investigated the physiological, anthropometric, and skill
      characteristics of rugby league players and determined the relationship between
      physical fitness and playing ability in these athletes. Eighty-six rugby league
      players (mean +/- SD age, 22.5 +/- 4.9 years) underwent measurements of standard
      anthropometry (height, body mass, and sum of 4 skinfolds), muscular power
      (vertical jump), speed (10-, 20-, and 40-m sprint), agility (L run), and
      estimated maximal aerobic power (multistage fitness test). In addition, 2 expert
      coaches independently assessed the playing ability of players using standardized
      skill criteria. First-grade players had significantly greater (p < 0.05) basic
      passing and ball-carrying ability and superior skills under fatigue, tackling and
      defensive skills, and evasion skills (i.e., ability to beat a player and 2 verse
      1 skills) than second-grade and third-grade players. While no significant (p >
      0.05) differences were detected among playing levels for body mass; skinfold
      thickness; height; 10-, 20-, or 40-m speed; agility; vertical jump height; or
      estimated maximal aerobic power, all the physiological and anthropometric
      characteristics were significantly (p < 0.05) associated with at least 1 measure
      of playing ability. The results of this study demonstrate that selected skill
      characteristics but not physiological or anthropometric characteristics
      discriminate between successful and less successful rugby league players.
      However, all physiological and anthropometric characteristics were related to
      playing ability. These findings suggest that while physiological and
      anthropometric characteristics do not discriminate between successful and less
      successful rugby league players, a high level of physical fitness contributes to
      effective playing ability in these athletes. A game-specific training program
      that incorporates both physical conditioning and skills training may facilitate a
      greater transfer of physical fitness to competitive performances in rugby league.

PMID- 18076243
TI  - Postactivation potentiation in professional rugby players: optimal recovery.
AB  - Following a bout of high-intensity exercise of short duration (preload stimulus),
      the muscle is in both a fatigued and a potentiated (referred to as postactivation
      potentiation) state. Consequently, subsequent muscle performance depends on the
      balance between these 2 factors. To date, there is no uniform agreement about the
      optimal recovery required between the preload stimulus and subsequent muscle
      performance to gain optimal performance benefits. The aim of the present study
      was to determine the optimal recovery time required to observe enhanced muscle
      performance following the preload stimulus. Twenty-three professional rugby
      players (13 senior international players) performed 7 countermovement jumps
      (CMJs) and 7 ballistic bench throws at the following time points after a preload
      stimulus (3 repetition maximum [3RM]): baseline, approximately 15 seconds, and 4,
      8, 12, 16, and 20 minutes. Their peak power output (PPO) was determined at each
      time point. Statistical analyses revealed a significant decrease in PPO for both
      the upper (856 +/- 121 W vs. 816 +/- 121 W, p < 0.001) and the lower (4,568 +/-
      509 W vs. 4,430 +/- 495 W, p = 0.005) body when the explosive activity was
      performed approximately 15 seconds after the preload stimulus. However, when 12
      minutes was allowed between the preload stimulus and the CMJ and ballistic bench
      throws, PPO was increased by 8.0 +/- 8.0% and 5.3 +/- 4.5%, respectively. Based
      on the above results, we conclude that muscle performance (e.g., power) can be
      significantly enhanced following a bout of heavy exercise (preload stimulus) in
      both the upper and the lower body, provided that adequate recovery (8-12 minutes)
      is given between the preload stimulus and the explosive activity.

PMID- 18076244
TI  - Effect of two different rest period lengths on the number of repetitions
      performed during resistance training.
AB  - The purpose of this study was to compare the effects of 2 different rest period
      lengths during a resistance training session with the number of repetitions
      completed per set of each exercise, the volume completed over 3 sets of each
      exercise, and the total volume during a training session. Fourteen experienced,
      weight-trained men volunteered to participate in the study. All subjects
      completed 2 experimental training sessions. Both sessions consisted of 3 sets of
      8 repetitions with an 8 repetition maximum resistance of 6 upper body exercises
      performed in a set manner (wide grip lat pull-down, close grip pull-down, machine
      seated row, barbell row lying on a bench, dumbbell seated arm curl, and machine
      seated arm curl). The 2 experimental sessions differed only in the length of the
      rest period between sets and exercises: 1 session with a 1-minute and the other
      with a 3-minute rest period. For all exercises, results demonstrate a
      significantly lower total number of repetitions for all 3 sets of an exercise
      when 1-minute rest periods were used (p < or = 0.05). The 3- and 1-minute
      protocols both resulted in a significant decrease from set 1 to set 3 in 4 of the
      6 exercises (p < or = 0.05), whereas the 1-minute protocol also demonstrated a
      significant decrease from set 1 to set 2 in 2 of the 6 exercises (p < or = 0.05).
      The results indicate that, during a resistance training session composed of all
      upper body exercises, 1-minute rest periods result in a decrease in the total
      number of repetitions performed compared with 3-minute rest periods between sets
      and exercises.

PMID- 18076245
TI  - Protection against muscle damage following fifty drop jumps conferred by ten drop
      jumps.
AB  - This study investigated whether 10 drop jumps (DJs) would confer protective
      effect against muscle damage and soreness in a subsequent bout of 50 DJs. Sixteen
      men were randomly placed into either a group performing 1 set of 10 DJs followed
      by 5 sets of 10 DJs (10-50, n = 8) or another group performing 2 bouts of 5 sets
      of 10 DJs (50-50, n = 8) separated by 2 weeks. The DJs were performed from a box
      height of 0.6 m, with a 10-second interval between jumps and a 1-minute rest
      between sets. Jump height, peak vertical ground reaction force, ground contact
      time, and heart rate during DJs were measured, and blood lactate concentration
      was assessed before and immediately after DJs. Changes in maximal isometric (ISO)
      and isokinetic concentric torque (CON), vertical jump, muscle soreness, and
      plasma creatine kinase activity before, immediately after, and at 1, 24, 48, and
      72 hours following exercise were compared between groups for the first and second
      bouts and between the bouts by a 2-way repeated-measures analysis of variance.
      Changes in ISO, CON, vertical jump, and muscle soreness were significantly (p <
      0.05) smaller for 10 DJs compared with 50 DJs; however, no significant
      differences in the measures between groups were evident following the second
      bout. The changes in the measures following 50 DJs in the 10-50 group were
      significantly (p < 0.05) smaller than those following the first bout of the 50-50
      group. These results suggest that 10 DJs and 50 DJs conferred the same magnitude
      of protective effect against muscle damage by 50 DJs.

PMID- 18076246
TI  - Creatine supplementation does not reduce muscle damage or enhance recovery from
      resistance exercise.
AB  - Previous studies have shown that creatine supplementation reduces muscle damage
      and inflammation following running but not following high-force, eccentric
      exercise. Although the mechanical strain placed on muscle fibers during high
      force, eccentric exercise may be too overwhelming for creatine to exert any
      protective effect, creatine supplementation may protect skeletal muscle stressed
      by a resistance training challenge that is more hypoxic in nature. The purpose of
      this study was to examine the effects of short-term creatine supplementation on
      markers of muscle damage (i.e., strength, range of motion, muscle soreness,
      muscle serum protein activity, C-reactive protein) to determine whether creatine
      supplementation offers protective effects on skeletal muscle following a hypoxic
      resistance exercise test. Twenty-two healthy, weight-trained men (19-27 years)
      ingested either creatine or a placebo for 10 days. Following 5 days of
      supplementation, subjects performed a squat exercise protocol (5 sets of 15-20
      repetitions at 50% of 1 repetition maximum [1RM]). Assessments of creatine kinase
      (CK) and lactate dehydrogenase activity, high-sensitivity C-reactive protein,
      maximal strength, range of motion (ROM), and muscle soreness (SOR) with movement
      and palpation were conducted pre-exercise and during a 5-day follow up. Following
      the exercise test, maximal strength and ROM decreased, whereas SOR and CK
      increased. Creatine and placebo-supplemented subjects experienced significant
      decreases in maximal strength (creatine: 13.4 kg, placebo: 17.5 kg) and ROM
      (creatine: 2.4 degrees , placebo: 3.0 degrees ) immediately postexercise, with no
      difference between groups. Following the exercise test, there were significant
      increases in SOR with movement and palpation (p < 0.05 at 24, 48, and 72 hours
      postexercise), and CK activity (p < 0.05 at 24 and 48 hours postexercise), with
      no differences between groups at any time. These data suggest that oral creatine
      supplementation does not reduce skeletal muscle damage or enhance recovery
      following a hypoxic resistance exercise challenge.

PMID- 18076247
TI  - Effects of short vs. long rest period between sets on elbow-flexor muscular
      endurance during resistance training to failure.
AB  - This study aimed to examine short-term resistance training effects of resting
      period length between sets on maximal number of repetitions and mean velocity
      over a moderate-intensity (60% of the maximum voluntary isometric contraction
      [MVIC]) set to failure on elbow-flexor muscles. The MVIC and surface
      electromyographic activity (sEMG) were also measured. Twenty-one untrained
      subjects were divided into 3 groups: short rest between sets (1 minute; SR), long
      rest between sets (4 minutes; LR), and nontraining control group (CG). The SR and
      LR performed 3 sets to failure in an arm-curl machine, 2 days per week for 5
      weeks, with moderate loads (60-75% of the MVIC). The LR completed a significantly
      higher (31.6%, p < 0.05) total training volume than the SR. Both training groups
      enhanced the maximal number of repetitions to failure, with no significant
      differences in the magnitude of gains. The posttraining average velocity achieved
      by the SR at 40, 50, 60, 70, 80, and 90% of the total number of repetitions
      completed was significantly higher (p < 0.05) than the corresponding average
      velocity achieved on pretraining conditions, whereas no significant differences
      were observed in the LR. No significant changes in the MVIC or sEMG were observed
      in any group. We conclude that short-term elbow-flexor resistance training to
      failure, allowing 1 or 4 minutes of rest between sets, induces similar gains
      concerning local muscular endurance. Nevertheless, only the SR training approach
      reduced the rate of decline in the average repetition velocity during a set to
      failure. This can be of some importance in sport modalities in which not only the
      maximal number of repetitions (e.g., muscle endurance), but also a greater
      maintenance of high repetition velocities, may be critical for performance.

PMID- 18076248
TI  - The effects of velocity-spectrum training on the ability to rapidly step.
AB  - Falls may occur because of a deficiency in the ability to rapidly step in the
      desired direction. Previous models developed to predict rapid step ability have
      been based on balance, video analysis, or uniplanar isokinetic performance. The
      purpose of this investigation was to determine the effects of multiplanar
      velocity-spectrum training of the hip. Seven males (23.14 years) and 16 females
      (23.75 years) were tested for peak torque, peak power, and rate of velocity
      development and on rapid step test (RST) measurements. Participants in the
      training group went through 8 training sessions over 4 weeks, consisting of
      unilateral hip flexion/extension and hip abduction/adduction of each leg, while
      the control group maintained regular activity throughout the 4-week span.
      Exercises were performed on a Biodex System 3 isokinetic dynamometer beginning at
      a speed of 60 degrees x sec(-1), gradually increasing in speed every week up to
      180, 300, and 400 degrees x s(-1), respectively. Analysis of the data revealed no
      significant (p < 0.05) differences between groups on any measure. However, the
      data showed a significant improvement in RST time (pre: 50.87 +/- 4.41 seconds;
      post: 49.20 +/- 4.28 seconds) and number of errors (pre: 4.13 +/- 2.87 errors;
      post: 2.75 +/- 1.81 errors), implying that a learning effect took place on the
      RST for all individuals. Additionally, short-term isokinetic training did not
      translate into significant results. It was concluded that 4 weeks of velocity
      spectrum training of the hip did not lead to improvements on the ability to
      rapidly step, as measured by the RST. Therefore, the open-kinetic-chain training
      should not be done for improvements on a functional, closed-kinetic-chain
      activity.

PMID- 18076249
TI  - Bilateral differences in the net joint torques during the squat exercise.
AB  - Bilateral movements are common in human movement, both as exercises and as daily
      activities. Because the movement patterns are similar, it is often assumed that
      there are no bilateral differences (BDs; differences between the left and right
      sides) in the joint torques that are producing these movements. The aim of this
      investigation was to test the assumption that the joint torques are equal between
      the left and right lower extremities by quantifying BDs during the barbell squat.
      Eighteen recreationally trained men (n = 9) and women (n = 9) completed 3 sets of
      3 repetitions of the squat exercise, under 4 loading conditions: 25, 50, 75, and
      100% of their 3 repetition maximum, while instrumented for biomechanical
      analysis. The average net joint moment (ANJM) and maximum flexion angle (MFA) for
      the hip, knee, and ankle as well as the average vertical ground reaction force
      (AVGRF) and the average distance from the ankle joint center to the center of
      pressure (ADCOP) were calculated. Group mean and individual data were analyzed
      (alpha = 0.05). At each joint, there was a significant main effect for side and
      load, no main effect for gender, with few significant interactions. The hip ANJM
      was 12.4% larger on the left side, the knee ANJM was 13.2% larger on the right
      side, and the ankle ANJM was 16.8% larger on the left side. Differences in MFAs
      between sides were less than 2 degrees for all 3 joints (all p > 0.20 except for
      the knee at 75% [p = 0.024] and 100% [p = 0.025]), but the AVGRF and the ADCOP
      were 6% and 11% larger on the left side. Few subjects exhibited the pattern
      identified with the group mean data, and no subject exhibited nonsignificant BDs
      for all 3 joints. These findings suggest that joint torques should not be assumed
      to be equal during the squat and that few individual subjects follow the pattern
      exhibited by group mean data.

PMID- 18076250
TI  - Comparison of cardiorespiratory responses of moderately trained men and women
      using two different treadmill protocols.
AB  - In practice, the Bruce protocol is the most commonly used treadmill protocol to
      assess maximal oxygen consumption (V(.-)O2max). It has been suggested that a
      running protocol (e.g., Astrand) may elicit a comparatively higher V(.-)O2max and
      different cardiorespiratory responses when applied to moderately trained runners.
      Thus, the purpose of this study was to compare V(.-)O2max and other
      cardiorespiratory responses as elicited by the standard Bruce and a modified
      Astrand treadmill protocol in moderately trained runners. Fifteen women (age = 21
      years, height = 171.5 cm, weight = 63 kg, and body fat = 18%) and 15 men (age =
      26 years, height = 177 cm, weight = 72 kg, and body fat = 9%) who were moderately
      trained runners completed a standard Bruce and modified Astrand protocol (random
      order), separated by approximately 7 days. Heart rate, Borg ratings of perceived
      exertion, blood pressure, and pulmonary gas exchange variables were measured
      during the exercise tests using standard laboratory procedures. This study
      revealed V(.-)O2max values between the Bruce protocol (51.3 +/- 11.6 ml x kg(-1)
      x min(-1)) and modified Astrand (51.5 +/- 10.9 ml x kg(-1) x min(-1)) were not
      significantly different in either the men or the women. However, the Bruce
      protocol elicited significantly higher maximum treadmill time in men and maximum
      respiratory exchange ratio (RERmax) and maximum minute ventilation (VEmax) values
      in both genders. Conversely, the modified Astrand elicited a higher HRmax. These
      data suggest that V(.-)O2max in both moderately trained men and women runners is
      independent of treadmill protocol despite differences in HRmax, RERmax, and
      VEmax.

PMID- 18076251
TI  - Effects of exercise order on upper-body muscle activation and exercise
      performance.
AB  - With the purpose of manipulating training stimuli, several techniques have been
      employed to resistance training. Two of the most popular techniques are the pre
      exhaustion (PRE) and priority system (PS). PRE involves exercising the same
      muscle or muscle group to the point of muscular failure using a single-joint
      exercise immediately before a multi-joint exercise (e.g., peck-deck followed by
      chest press). On the other hand, it is often recommended that the complex
      exercises should be performed first in a training session (i.e., chest press
      before peck-deck), a technique known as PS. The purpose of the present study was
      to compare upper-body muscle activation, total repetitions (TR), and total work
      (TW) during PRE and PS. Thirteen men (age 25.08 +/- 2.58 years) with recreational
      weight-training experience performed 1 set of PRE and 1 set of PS in a balanced
      crossover design. The exercises were performed at the load obtained in a 10
      repetition maximum (10RM) test. Therefore, chest press and peck-deck were
      performed with the same load during PRE and PS. Electromyography (EMG) was
      recorded from the triceps brachii (TB), anterior deltoids, and pectoralis major
      during both exercises. According to the results, TW and TR were not significantly
      different (p > 0.05) between PRE and PS. Likewise, during the peck-deck exercise,
      no significant (p > 0.05) EMG change was observed between PRE and PS order.
      However, TB activity was significantly (p < 0.05) higher when chest press was
      performed after the peck-deck exercise (PRE). Our findings suggest that
      performing pre-exhaustion exercise is no more effective in increasing the
      activation of the prefatigued muscles during the multi-joint exercise. Also,
      independent of the exercise order (PRE vs. PS), TW is similar when performing
      exercises for the same muscle group. In summary, if the coach wants to maximize
      the athlete performance in 1 specific resistance exercise, this exercise should
      be placed at the beginning of the training session.

PMID- 18076253
TI  - Kinematics and kinetics of the seated row and implications for conditioning.
AB  - Optimizing transference of gym-based strength and power gains to sporting
      performance necessitates a physiological and biomechanical understanding of the
      weight-training exercise as well as the sporting activity. With this in mind,
      this paper describes the kinematics and kinetics associated with a seated row.
      The maximal strength and concentric power-load spectrum (30- 100% 1 repetition
      maximum [1RM]) for the cable seated row was assessed using Olympic rowers (n =
      8). In terms of temporal characteristics, peak force across all loads occurred
      within the first 25% of movement time. Peak power across loads occurred within 35
      45% of movement time. With regard to position, peak force occurred within 8.3%
      and peak power within 27-35% of the start of the concentric phase. To estimate
      the load that maximized mechanical power output, a quadratic was fitted to each
      subject's power output vs. 1RM. In terms of mean power, an estimated load of
      81.4% (+/- 9.7%) 1RM was found to maximize power output. A 10 and 20% change in
      load each side of this maximum resulted in a 1.8 and 7.3% decrease in power
      output, respectively. The predilection of research to train all subjects at 1
      load is fundamentally flawed due to interindividual maximum power differences
      (range in this study = 69-100% 1RM). Also, the importance of this measure would
      seem questionable, given that loads either side of the load that maximize power
      output do not change power output substantially.

PMID- 18076252
TI  - Metabolic and performance effects of raisins versus sports gel as pre-exercise
      feedings in cyclists.
AB  - Research suggests that pre-exercise sources of dietary carbohydrate with varying
      glycemic indexes may differentially affect metabolism and endurance. This study
      was designed to examine potential differences in metabolism and cycling
      performance after consumption of moderate glycemic raisins vs. a high glycemic
      commercial sports gel. Eight endurance-trained male (n = 4) and female (n = 4)
      cyclists 30 +/- 5 years of age completed 2 trials in random order. Subjects were
      fed 1 g carbohydrate per kilogram body weight from either raisins or sports gel
      45 minutes prior to exercise on a cycle ergometer at 70% V(.-)O2max. After 45
      minutes of submaximal exercise, subjects completed a 15-minute performance trial.
      Blood was collected prior to the exercise bout, as well as after the 45th minute
      of exercise, to determine serum concentrations of glucose, insulin, lactate, free
      fatty acids (FFAs), triglycerides, and beta-hydroxybutyrate. Performance was not
      different (p > 0.05) between the raisin (189.5 +/- 69.9 kJ) and gel (188.0 +/-
      64.8 kJ) trials. Prior to exercise, serum concentrations of glucose and other
      fuel substrates did not differ between trials; however, insulin was higher (p <
      0.05) for the gel (110.0 +/- 70.4 microU x ml(-1)) vs. raisin trial (61.4 +/-
      37.4 microU x ml(-1)). After 45 minutes of exercise, insulin decreased to 14.2 +/
      6.2 microU x ml(-1) and 13.3 +/- 18.9 microU x ml(-1) for gel and raisin trials,
      respectively. The FFA concentration increased (+0.2 +/- 0.1 mmol x L(-1))
      significantly (p < 0.05) during the raisin trial. Overall, minor differences in
      metabolism and no difference in performance were detected between the trials.
      Raisins appear to be a cost-effective source of carbohydrate for pre-exercise
      feeding in comparison to sports gel for short-term exercise bouts.

PMID- 18076254
TI  - Correlates of knee extensor training load used in rehabilitation after knee
      surgery.
AB  - Resistance training is one of the major components of rehabilitation after
      musculoskeletal injury and surgery. Despite the importance of resistance training
      and the frequency of its use in rehabilitation, little is known about factors
      that are related to training load that might be useful in devising and monitoring
      training in a patient and comparing training intensities between individuals and
      groups. We hypothesized that the following would show a statistically significant
      relationship to training load: injury chronicity, self-assessed knee function
      (Hughston Clinic questionnaire), knee swelling (injured-uninjured midpatellar
      knee girth), uninjured knee girth, and body mass. The purpose of this study was
      to evaluate whether factors such as body mass are related to the load used in
      training the knee extensors in rehabilitation after knee surgery. Thirty-six
      individuals undergoing early-phase rehabilitation after knee arthroscopic
      meniscectomy surgery participated in this study. Subjects were tested 5 days
      after surgery, just prior to commencing a 6-week outpatient rehabilitation
      program, and again soon after the end of this rehabilitation program. The
      independent variables evaluated were age, gender, body mass, meniscus injured,
      injury chronicity, knee function self-assessment, knee swelling (injured
      uninjured midpatellar girth), uninjured knee girth, and knee flexion and
      extension passive range of motion (difference between injured and uninjured
      side). The dependent variable was the load used for training the knee extensors
      on the knee extension machine in the final training session prior to the
      posttest. The only variable exhibiting a statistically significant (p = 0.001)
      relationship to knee extensor final training was age (r = -0.529). This finding,
      that age was the only variable to have a significant relationship with training
      load, suggests that clinicians' expectation of training intensity should decrease
      with an increase in the patient's age in the range studied (20-58 years) for
      patients recovering from knee arthroscopic meniscectomy.

PMID- 18076255
TI  - Postactivation potentiation effects after heavy resistance exercise on running
      speed.
AB  - The purpose of this study was to investigate the postactivation potentiation
      effect after a heavy resistance stimulus (HRS) on running speed (RS). Fifteen
      amateur team game players (basketball, volleyball, handball, and soccer players),
      ages 18-23 years running the 30-m dash and the intermediate phase of 0-10 and 0
      30 m sprints, were used to evaluate RS. Resistance training consisted of 10
      single repetitions at 90% of 1 repetition maximum. The running tests were
      performed 3 times--(a) 3 minutes prior the HRS, (b) 3 minutes after the HRS, and
      (c) 5 minutes after the HRS--in separated training sessions. Results showed that
      RS was not affected 3 minutes after the resistance training, but it increased for
      both selected running phases (0-10 and 0-30 m) 5 minutes after the HRS (p <
      0.05). These findings indicate that heavy resistance exercise improves 10- and 30
      m sprint performance when performed 5 minutes after the exercise bout.

PMID- 18076256
TI  - Does hyperbaric oxygen exposure affect high-intensity, short-duration exercise
      performance?
AB  - Hyperbaric oxygen (HBO) exposure involves the breathing of 100% oxygen under
      conditions of elevated atmospheric pressure and is used to increase the oxygen
      content of the plasma fraction of arterial blood. The purpose of this study was
      to determine the effects of acute HBO exposure on selected physiological
      responses and performance in response to maximal lower extremity or upper
      extremity short-term, high-intensity exercise. The study was performed with 2
      separate experiments incorporating double-blinded and randomized protocols. In
      experiment 1, 9 subjects ran on a treadmill at a speed of 268 m x min(-1) with a
      predetermined grade. In experiment 2, 9 different subjects performed a repetitive
      bench press exercise. Both exercise protocols were designed to induce fatigue
      within 1-2 minutes. Within each experiment, subjects received either a 1-hour HBO
      exposure inspiring 100% O2 at 202.6 kPa (2.0 atmospheres absolute pressure [ATA])
      or a 1-hour sham exposure inspiring ambient air at 121.5 kPa (1.2 ATA) before
      exercise. No significant differences (p > or = 0.05) were observed in
      postexercise blood lactate concentrations, peak heart rate, ratings of perceived
      exertion, or performance as determined by treadmill running time or number of
      completed lifts. Unlike other methods that elevate oxygen content of the blood,
      acute HBO exposure appears to have no significant effect on subsequent high
      intensity running or lifting performance.

PMID- 18076257
TI  - Analysis of acute explosive training modalities to improve lower-body power in
      baseball players.
AB  - Complex training is the simultaneous combination of heavy resistance training and
      plyometrics. The objective of this study was to test the effects of complex
      training vs. heavy resistance or plyometric interventions alone on various power
      specific performance measures. Forty-five male division II junior college
      baseball players participated in 3 separate 4-week resistance training
      interventions. Subjects were randomly assigned to one of three groups. In a
      counterbalanced rotation design, each group participated in complex, heavy
      resistance, and plyometric training interventions. Each individual was tested in
      20-yd (SP20), 40-yd (SP40), 60-yd (SP60), vertical jump, standing broad jump, and
      T-agility measures pre- and post-4-week training interventions. There was no
      statistical significant difference (p = 0.11) between groups across all
      performance measures. Review of each distinct training intervention revealed
      greater percent improvements in SP20 (0.55; -0.49; -0.12), SP40 (0.26; -0.72; 
      1.33), SP60 (0.27; 0.15; -0.27), standing broad jump (1.80; 0.67; 1.1), and T
      agility (2.33; 1.23; -0.04) with complex training interventions than with the
      heavy resistance or plyometric training interventions, respectively. Plyometric
      only training showed greater percent changes in vertical jump (1.90) than with
      complex (0.97) or heavy resistance training (0.36). The present results indicate
      that complex training can provide strength and conditioning professionals equal,
      if not slightly greater, improvements in muscular power than traditional heavy
      resistance- and plyometric-only interventions in moderately trained athletes.
      Complex training can be another valuable method for short-term power and speed
      improvements in athletes in isolation or in conjunction with other power
      development methods.

PMID- 18076258
TI  - Power outputs of a machine squat-jump across a spectrum of loads.
AB  - The load that maximizes mechanical power output (Pmax) has received considerable
      research attention owing to its perceived importance to training prescription.
      However, it may be that identifying Pmax is of little importance if the
      difference in power output about Pmax is insubstantial. Additionally, comparing
      the effect of load on power output between studies is problematic due to various
      methodological differences. The purpose of this study therefore was to quantify
      the concentric power output for a machine squat-jump across a spectrum of loads
      (10-100% of 1 repetition maximum [1RM]). To estimate Pmax load and proximate
      loads a quadratic was fitted to the power output (Watts) and load (% of 1RM) of
      18 well-trained rugby athletes. Pmax for peak and mean power output occurred at
      21.6 +/- 7.1% of 1RM (mean +/- SD) and 39.0 +/- 8.6% of 1RM, respectively. A 20%
      change in load either side of the maximum resulted in a mean decrease of only
      9.9% (90% confidence limits +/-2.4%) and 5.4% (+/-0.9%) in peak and mean power
      respectively; standard deviations about these means (representing individual
      differences in the decrease) were 6.0% and 2.1%, respectively (90% confidence
      limits x//1.34). It appears that most athletes have a broad peak in their power
      profile for peak or mean power. The preoccupation of identifying one load for
      maximizing power output would seem less meaningful than many practitioners and
      scientists believe.

PMID- 18076259
TI  - Relationship between optimal lactate removal power output and Olympic triathlon
      performance.
AB  - To investigate the relationships between race performance and parameters at the
      optimal power output for lactate removal, 10 male triathletes were examined.
      Exercise intensities for lactate removal were defined by calculating 50% of
      difference (DeltaT) between running velocity (V(r)) at individual anaerobic
      threshold (IAT) and at individual ventilatory threshold (IVT), then choosing 3
      V(r): at IVT plus 50% DeltaT (IVT(+50%DeltaT)), at IVT, and at IVT minus 50%
      DeltaT (IVT(-50%DeltaT)). After a 6-minute treadmill run at 75% of difference
      between IAT and V(.-)O2max, all triathletes performed a 30-minute active recovery
      run at IVT(+50%DeltaT), IVT, and IVT(-50%DeltaT). Capillary blood lactate was
      determined at 1, 3, 6, 9, 12, 15, 20, 25, and 30 minutes of recovery. The IVT(
      50%DeltaT) recovery was the most efficient V(r) for lactate removal. Running
      velocities at IVT and IVT(-50%DeltaT) were highly (p < 0.01) related to cycle,
      run, and overall race time. V(.-)O2max values at IAT, IVT(+50%DeltaT), and IVT
      were less (p < 0.05) related to split and overall race time. The variable most
      related to overall race time, as determined by stepwise multiple linear
      regression analysis, was the V(r) at IVT(-50%DeltaT) (r = 0.87, p = 0.001). The
      R(2) value of 0.76 indicated that V(r) at IVT(-50%DeltaT) could account for 76%
      of the variance in triathlon race time. This study shows that the race
      performances of triathletes are highly related to the V(r) at which the most
      efficient lactate removal (IVT(-50%DeltaT)) occurs. These findings suggest that
      the assessment of V(r) at IVT and IAT (from which V(r) at IVT(-50%DeltaT) are
      calculated) may be a useful method for monitoring training-induced adaptations
      and performance improvements in athletes who participate in Olympic triathlons.

PMID- 18076260
TI  - Acute effects of dynamic stretching exercise on power output during concentric
      dynamic constant external resistance leg extension.
AB  - The purpose of the present study was to clarify the acute effect of dynamic
      stretching exercise on muscular performance during concentric dynamic constant
      external resistance (DCER, formally called isotonic) muscle actions under various
      loads. Concentric DCER leg extension power outputs were measured in 12 healthy
      male students after 2 types of pretreatment. The pretreatments were: (a) dynamic
      stretching treatment including 2 types of dynamic stretching exercises of leg
      extensors and the other 2 types of dynamic stretching exercises simulating the
      leg extension motion (2 sets of 15 times each with 30-second rest periods between
      sets; total duration: about 8 minutes), and (b) nonstretching treatment by
      resting for 8 minutes in a sitting position. Loads during measurement of the
      power output were set to 5, 30, and 60% of the maximum voluntary contractile
      (MVC) torque with isometric leg extension in each subject. The power output after
      the dynamic stretching treatment was significantly (p < 0.05) greater than that
      after the nonstretching treatment under each load (5% MVC: 468.4 +/- 102.6 W vs.
      430.1 +/- 73.0 W; 30% MVC: 520.4 +/- 108.5 W vs. 491.0 +/- 93.0 W; 60% MVC: 487.1
      +/- 100.6 W vs. 450.8 +/- 83.7 W). The present study demonstrated that dynamic
      stretching routines, such as dynamic stretching exercise of target muscle groups
      and dynamic stretching exercise simulating the actual motion pattern,
      significantly improve power output with concentric DCER muscle actions under
      various loads. These results suggested that dynamic stretching routines in warm
      up protocols enhance power performance because common power activities are
      carried out by DCER muscle actions under various loads.

PMID- 18076261
TI  - Efficacy of prior eccentric exercise in attenuating impaired exercise performance
      after muscle injury in resistance trained men.
AB  - Previous research has demonstrated that prior exercise may reduce the magnitude
      of muscle soreness and impaired function (i.e., repeated bout effect [RBE])
      observed during subsequent eccentric exercise. Previous investigations have
      predominantly used research designs that include single-joint exercise performed
      by untrained individuals. It is unknown how resistance trained individuals
      respond to novel multi-joint eccentric actions of the upper body and whether
      prior exercise offers protection. Thirty-one resistance trained men (23.4 +/- 3.5
      y, 177.2 +/- 5.1 cm, 86.4 +/- 16.5 kg, mean +/- SD) were randomly assigned to
      repeated bout ([RB] N = 15) or single bout ([CON] N = 16) conditions. Both groups
      performed 100 eccentric actions of the bench press ([ECC] at 70% concentric 1
      repetition maximum) to induce muscle injury. Bilateral maximal isometric force,
      dynamic exercise performance (e.g., bench press throws), and muscle soreness were
      measured before, immediately after, and at 24 and 48 hours post-ECC. Total work,
      percent fatigue, and rating of perceived exertion (ECC) data were collected
      during ECC. Those assigned to RB condition exhibited less fatigue (9.5 vs. 22.6%)
      and lower RPE (14.8 vs. 17.1) during ECC. A significant interaction (p < 0.05)
      was found such that RB individuals experienced less soreness at 24 (6.5 vs. 4.9)
      and 48 (6.6 vs. 3.9) hours postexercise than the CON condition. No significant
      group differences (p < 0.05) were found for any measured performance variable.
      Although soreness, fatigue, and RPE suggest a RBE, this was not found in regards
      to exercise performance. It appears that in trained men, performing a strenuous
      high-volume eccentric exercise bout 2 weeks prior to an identical future bout
      offers no additional amelioration of impaired exercise performance.

PMID- 18076262
TI  - Specificity of machine, barbell, and water-filled log bench press resistance
      training on measures of strength.
AB  - The purpose of this study was to compare the effects of 10 weeks of resistance
      training with an isotonic bench press machine and 2 types of free-weight bench
      press exercises on several measures bench press strength. Specificity was
      investigated by comparing the ability to transfer strength gained from a type of
      training that differed from the mode of testing. Forty-nine men participated in
      the study. The subjects completed a pretest on the machine (MB), barbell (BB),
      isokinetic (IB), and log (LB) bench press to determine baseline strength and
      completed 10 weeks of training on the MB, BB, or LB. The 3 groups were tested to
      see whether differential training effects occurred from pre- to posttest scores
      on the BB, MB, LB, and peak force on the IB. By multivariate analysis, the trial
      by-group interaction was not statistically significant. The multivariate and
      subsequent univariate analyses of variance tests indicated statistically
      significant effects from pre- to posttest for peak force on the IB test and the
      BB, MB, and LB. Correlations among the strength tests were high (0.92 > or = r <
      or = 0.97) and moderate between the strength tests and IB peak force (0.62 > or =
      r < pr = 0.83). Mean 3 repetition maximum MB strength was 8% higher than BB
      strength, which was 3% higher than LB strength, indicating differences in the
      amount of stabilization required to control the resistance. The findings of this
      study showed that all 3 training groups significantly improved in strength during
      short-term training on the MB, BB, and LB. These data lend evidence that improved
      strength after training on the MB, BB, and LB equally transfers to strength gains
      on any of the 4 modes of testing. These results should be considered when
      including similar exercises varying in stability into the training program to
      improve strength.

PMID- 18076263
TI  - Effect of active recovery on acute strength deficits induced by passive
      stretching.
AB  - We herein examined whether immediate muscular activity (active recovery) after
      stretching decreased stretch-induced strength deficits in human muscles. Our
      within-subject study included 8 subjects who were used as their own controls. For
      each subject, both legs were subjected to the same warm-up and stretching
      treatments, and then one leg was exposed to active recovery (experimental
      treatment) while the other was allowed to recover passively (control). Unilateral
      maximal voluntary contraction (MVC) of knee extensors was measured at baseline,
      poststretching, and postrecovery to monitor strength evolution. Our results
      revealed that the MVC strength at the baseline time point for control (590.8 +/-
      104.2) and treated (602.2 +/- 112.7) legs decreased poststretching by 8.0 and
      8.9%, respectively, and further decreased postrecovery by 1.3 and 1.2%,
      respectively. Maximal voluntary contraction strength tests demonstrated very good
      reliability, having intraclass coefficients of correlation ranging from 0.92
      0.98. Mixed analysis of variance showed that the stretching program yielded
      significantly increased flexibility (p < 0.01) and significantly decreased MVC (p
      < 0.001) in both legs. The over-time variability between legs was marginal (1%),
      and no significant between-leg differences were observed. Indeed, the improvement
      in strength restoration due to active vs. passive recovery was -0.5 +/- 15 N,
      which was significantly lower (p < 0.01; 1-tailed t-test) than the amount of
      strength inhibition (32.6 N), estimated as 60% of the overall strength deficit
      (54.3 +/- 29.7 N). These results confirm that significant strength is lost
      poststretching but fail to show greater improvement in strength following active
      vs. passive recovery. Collectively, the present findings indicate that, contrary
      to the belief of many coaches, muscular exercises during the poststretching
      period are unlikely to minimize stretch-induced strength deficits.

PMID- 18076264
TI  - Evaluation of jump protocols to assess leg power and predict hockey playing
      potential.
AB  - The purposes of this study were (a) to determine the measurement device and
      jumping protocol most appropriate for testing the leg power of elite hockey
      players and (b) to assess the relationship of leg power measurements to hockey
      playing ability as indicated by draft selection order. Comparisons were made of
      leg power measurements from the top 95 players entering the National Hockey
      League Entry Draft using 2 devices (Vertec and Just Jump) and 2 jump protocols
      (countermovement and squat). Players' leg powers were ranked from highest to
      lowest power using each device and protocol and were correlated with draft
      selection order. Vertec leg power measurements were highest (5,511-5,631 W), but
      there were no significant differences in power between the 2 jumping protocols on
      either device. Vertec squat jump provided the highest correlation (0.47) between
      leg power ranking and selection order and was judged to most closely approximate
      the full-body coordinated movements involved in hockey. The Vertec device using a
      squat jump protocol is most appropriate for coaches and fitness specialists to
      use when evaluating hockey potential based on the off-ice leg power measurements
      of elite hockey players.

PMID- 18076265
TI  - Validity of two alternative systems for measuring vertical jump height.
AB  - Vertical jump height is frequently used by coaches, health care professionals,
      and strength and conditioning professionals to objectively measure function. The
      purpose of this study is to determine the concurrent validity of the jump and
      reach method (Vertec) and the contact mat method (Just Jump) in assessing
      vertical jump height when compared with the criterion reference 3-camera motion
      analysis system. Thirty-nine college students, 25 females and 14 males between
      the ages of 18 and 25 (mean age 20.65 years), were instructed to perform the
      countermovement jump. Reflective markers were placed at the base of the
      individual's sacrum for the 3-camera motion analysis system to measure vertical
      jump height. The subject was then instructed to stand on the Just Jump mat
      beneath the Vertec and perform the jump. Measurements were recorded from each of
      the 3 systems simultaneously for each jump. The Pearson r statistic between the
      video and the jump and reach (Vertec) was 0.906. The Pearson r between the video
      and contact mat (Just Jump) was 0.967. Both correlations were significant at the
      0.01 level. Analysis of variance showed a significant difference among the 3
      means F(2,235) = 5.51, p < 0.05. The post hoc analysis showed a significant
      difference between the criterion reference (M = 0.4369 m) and the Vertec (M =
      0.3937 m, p = 0.005) but not between the criterion reference and the Just Jump
      system (M = 0.4420 m, p = 0.972). The Just Jump method of measuring vertical jump
      height is a valid measure when compared with the 3-camera system. The Vertec was
      found to have a high correlation with the criterion reference, but the mean
      differed significantly. This study indicates that a higher degree of confidence
      is warranted when comparing Just Jump results with a 3-camera system study.

PMID- 18076266
TI  - Core stabilization exercises enhance lactate clearance following high-intensity
      exercise.
AB  - Dynamic activities such as running, cycling, and swimming have been shown to
      effectively reduce lactate in the postexercise period. It is unknown whether core
      stabilization exercises performed following an intense bout would exhibit a
      similar effect. Therefore, this study was designed to assess the extent of the
      lactate response with core stabilization exercises following high-intensity
      anaerobic exercise. Subjects (N = 12) reported twice for testing, and on both
      occasions baseline lactate was obtained after 5 minutes of seated rest. Subjects
      then performed a 30-second Wingate anaerobic cycle test, immediately followed by
      a blood lactate sample. In the 5-minute postexercise period, subjects either
      rested quietly or performed core stabilization exercises. A final blood lactate
      sample was obtained following the 5-minute intervention period. Analysis revealed
      a significant interaction (p = 0.05). Lactate values were similar at rest (core =
      1.4 +/- 0.1, rest = 1.7 +/- 0.2 mmol x L(-1)) and immediately after exercise
      (core = 4.9 +/- 0.6, rest = 5.4 +/- 0.4 mmol x L(-1)). However, core
      stabilization exercises performed during the 5-minute postexercise period reduced
      lactate values when compared to rest (5.9 +/- 0.6 vs. 7.6 +/- 0.8 mmol x L(-1)).
      The results of this study show that performing core stabilization exercises
      during a recovery period significantly reduces lactate values. The reduction in
      lactate may be due to removal via increased blood flow or enhanced uptake into
      the core musculature. Incorporation of core stability exercises into a cool-down
      period following muscular work may result in benefits to both lactate clearance
      as well as enhanced postural control.

PMID- 18076267
TI  - The acute effects of twenty-four hours of sleep loss on the performance of
      national-caliber male collegiate weightlifters.
AB  - Currently, the degree to which sleep loss influences weightlifting performance is
      unknown. This study compared the effects of 24 hours of sleep loss on
      weightlifting performance and subjective ratings of psychological states pre
      exercise and postexercise in national-caliber male collegiate weightlifters. Nine
      males performed a maximal weightlifting protocol following 24 hours of sleep loss
      and a night of normal sleep. The subjects participated in a randomized,
      counterbalanced design with each sleep condition separated by 7 days.
      Testosterone and cortisol levels were quantified prior to, immediately after, and
      1 hour after the resistance training session. Additionally, profile of mood
      states and subjective sleepiness were evaluated at the same time points. The
      resistance training protocol consisted of several sets of snatches, clean and
      jerks, and front squats. Performance was evaluated as individual exercise volume
      load, training intensity and overall workout volume load, and training intensity.
      During each training session the maximum weight lifted for the snatch, clean and
      jerk, and front squat were noted. No significant differences were found for any
      of the performance variables. A significant decrease following the sleep
      condition was noted for cortisol concentration immediately after and 1 hour
      postexercise. Vigor, fatigue, confusion, total mood disturbance, and sleepiness
      were all significantly altered by sleep loss. These data suggest that 24 hours of
      sleep loss has no adverse effects on weightlifting performance. If an athlete is
      in an acute period of sleep loss, as noticed by negative mood disturbances, it
      may be more beneficial to focus on the psychological (motivation) rather than the
      physiological aspect of the sport.

PMID- 18076268
TI  - The influence of body mass on calculation of power during lower-body resistance
      exercises.
AB  - The objective of this investigation was to examine the influence of body mass in
      the calculation of power and the subsequent effect on the load-power relationship
      in the jump squat, squat, and power clean. Twelve Division I male athletes were
      evaluated on their performance across various intensities in all the 3 lifts.
      Power output was calculated using 3 separate techniques: (a) including the
      contribution of body mass in force output (IBM), (b) including the contribution
      of the mass of body less the mass of the shanks and feet in force output (IBMS),
      and (c) excluding the contribution of body mass in force output (EBM). Peak
      power, peak power relative to body mass, and peak force calculated using EBM were
      significantly (p < or = 0.05) lower than outputs calculated with IBM and IBMS.
      The load that maximized power output was unchanged between the 3 techniques in
      the jump squat (0% 1 repetition maximum [1RM]) and power clean (80% 1RM) but was
      shifted from 56% (IBM and IBMS) to 71% 1RM (EBM) in the squat. Across all 3
      movements, the shape of the load-power curve was affected when derived via the
      EBM method as a result of the underrepresentation of power output at light loads.
      This was due to the majority of the load being neglected when the mass of the
      body was removed from the system mass used in the calculation of force. This
      study indicates that not only is the actual power output significantly lower when
      body mass is excluded from the force output of a lower body movement, but the
      load-power relationship is altered as well. Therefore, it is imperative that the
      mass of the individual being tested is incorporated into the calculation of force
      used to determine power output during lower-body movements.

PMID- 18076269
TI  - The combined effects of protein intake and resistance training on serum
      osteocalcin concentrations in strength and power athletes.
AB  - The purpose of the present investigation was to examine the combined effects of
      protein intake and resistance training on a blood marker of bone osteogenesis,
      serum osteocalcin, in Division III football players. Thirty-three resistance
      trained football players (age = 20.4 +/- 1.8 years; height = 180.9 +/- 7.0 cm;
      body mass = 97.2 +/- 12.6 kg) were evaluated on their protein intake and
      subsequently underwent 10 weeks of periodized heavy resistance training during
      the off season. Subjects were then placed into 1 of the following 3 groups based
      on relative protein intake and were instructed to maintain their diets throughout
      the experimental period: (a) low protein intake (<1.2 g per kilogram of body
      mass), (b) moderate protein intake (1.21 to 1.90 g per kilogram of body mass), or
      (c) high protein intake (>1.91 g per kilogram of body mass). Blood sampling
      occurred prior to and following the 10-week resistance training period to
      determine resting serum osteocalcin concentrations. A significant main effect was
      observed following training such that only the group who consumed <1.2 g per
      kilogram of body mass of protein shown significant elevations in serum
      osteocalcin in response to resistance training (26.8 +/- 6.4 to 33.4 +/- 6.6
      ng.ml(-1)). In addition, absolute protein intake was significantly correlated to
      serum osteocalcin concentrations (r = 0.39). The results of the present
      investigation demonstrated relationships between protein intake and serum
      osteocalcin concentrations. In addition, the osteocalcin response to short-term
      resistance training appeared to be affected by protein intake.

PMID- 18076270
TI  - Strength, flexibility, and balance characteristics of highly proficient golfers.
AB  - Despite the emergence of golf-specific training programs and training aids,
      relatively little research has been conducted examining the physical
      characteristics that are important to golf performance. We studied the strength,
      flexibility, and balance characteristics of golfers across 3 proficiency levels
      based on handicap index (HCP) (<0, 1-9, and 10-20) to determine the physical
      characteristics unique to highly proficient golfers. A total of 257 (age: 45.5 +/
      12.8 years, height: 180.6 +/- 6.5 cm, weight: 87.9 +/- 12.6 kg) healthy, male
      golfers participated in the study. Testing included an assessment of strength
      (torso, shoulder, and hip), flexibility (torso, shoulder, and hip), and single
      leg balance. Golfers in the highest proficiency group (HCP < 0) had significantly
      (p < 0.05) greater hip strength, torso strength, shoulder strength, shoulder
      flexibility, hip flexibility, torso flexibility, and balance (eyes open) than
      golfers in the lowest proficiency group (HCP 10-20). The results of this study
      demonstrate that better golfers possess unique physical characteristics that are
      important to greater proficiency. These characteristics have also been
      demonstrated to be modifiable through golf-specific training programs.

PMID- 18076271
TI  - Relationship between cycling mechanics and core stability.
AB  - Core stability has received considerable attention with regards to functional
      training in sports. Core stability provides the foundation from which power is
      generated in cycling. No research has described the relationship between core
      stability and cycling mechanics of the lower extremity. The purpose of this study
      was to determine the relationship between cycling mechanics and core stability.
      Hip, knee, and ankle joint kinematic and pedal force data were collected on 15
      competitive cyclists while cycling untethered on a high-speed treadmill. The
      exhaustive cycling protocol consisted of cycling at 25.8 km x h(-1) while the
      grade was increased 1% every 3 minutes. A core fatigue workout was performed
      before the second treadmill test. Total frontal plane knee motion (test 1: 15.1
      +/- 6.0 degrees ; test 2: 23.3 +/- 12.5 degrees), sagittal plane knee motion
      (test 1: 69.9 +/- 4.9 degrees ; test 2: 79.3 +/- 10.1 degrees), and sagittal
      plane ankle motion (test 1: 29.0 +/- 8.5 degrees ; test 2: 43.0 +/- 22.9 degrees)
      increased after the core fatigue protocol. No significant differences were
      demonstrated for pedaling forces. Core fatigue resulted in altered cycling
      mechanics that might increase the risk of injury because the knee joint is
      potentially exposed to greater stress. Improved core stability and endurance
      could promote greater alignment of the lower extremity when riding for extended
      durations as the core is more resistant to fatigue.

PMID- 18076272
TI  - Aerobic run training improves brachial artery flow-mediated dilation.
AB  - The purpose of this study was to assess the relationship between aerobic exercise
      training and brachial artery flow-mediated dilation (FMD) in healthy subjects.
      Healthy controls (HC) and aerobically-trained (T) subjects were studied with high
      resolution vascular ultrasound at baseline, and during a 5-minute period of
      hyperemia following forearm cuff occlusion. Training was defined by self-reported
      participation in recreational or competitive run training. Forearm cuff occlusion
      was held at 200 mm Hg for 5 minutes. At baseline, both brachial artery flow and
      diameter were greater in T than in HC (p < 0.05). Resting heart rate was lower in
      T than in HC (p < 0.05). Peak hyperemic flow (15 seconds postocclusion) was
      significantly greater in T than in HC (HC; 539 +/- 75 ml x min(-1) vs. T; 832 +/-
      103 ml x min(-1), p < 0.05) and correlated well with V(.-)O2peak (r = 0.67, p =
      0.008). Flow-mediated dilation was significantly greater in T vs. HC throughout
      the 5-minute postocclusion phase (p < 0.05). Maximal brachial artery dilation was
      greater in T than in HC (HC; 3 +/- 1% of baseline vs. T; 8 +/- 3% of baseline; p
      < 0.05) and moderately correlated with V(.-)O2peak (r = 0.55, p < 0.05). These
      data suggest that the greater FMD observed in trained subjects may be due, in
      part, to an augmentation of peak hyperemic flow.

PMID- 18076273
TI  - The effect of single versus multiple sets on strength.
AB  - Research has previously been divided on whether performing resistance training
      with a single set per training session is as effective for increasing strength as
      training with multiple sets. The purpose of this study was to determine the
      effect of single sets versus multiple sets on strength. Forty subjects were
      randomly assigned into 1 of 3 groups: control (C; n = 8), single set (SS; n =
      14), or multiple sets (MS; n = 18) to perform 8 maximal knee extensions at 60
      degrees .s(-1) on a Biodex System 3 isokinetic dynamometer twice a week for 8
      weeks. The SS group performed 1 set while the MS group performed 3 sets. All
      groups were pre-, mid- (4 weeks), and posttested at 60 degrees x s(-1). Strength
      was expressed as peak torque (PT). A 3 x 3 x 2 (time x group x sex) mixed factor
      repeated measures analysis of variance (ANOVA) revealed no interaction involving
      sex, but there was an interaction of group by time. The MS group exhibited a
      significant (p < 0.05) increase in PT (pre = 171.39 +/- 61.98 Nm; mid = 193.08 +/
      66.23 Nm) between the pretest and the midtest while the SS (pre = 163.45 +/-
      56.37 Nm; mid = 172.60 +/- 61.78 Nm) and C groups (pre = 135.997 +/- 54.31 Nm;
      mid = 127.66 +/- 53.12 Nm) did not change. Strength did not change between the
      midtest and the posttest for any group. It was concluded that performing 3 sets
      of isokinetic knee extensions was more effective than performing a single set for
      increasing peak torque. These results seem to indicate that for increasing
      strength of the quadriceps, performing multiple sets is superior to performing a
      single set of resistance exercise.

PMID- 18076274
TI  - Change in power output across a high-repetition set of bench throws and jump
      squats in highly trained athletes.
AB  - Athletes experienced in maximal-power and power-endurance training performed 1
      set of 2 common power training exercises in an effort to determine the effects of
      moderately high repetitions upon power output levels throughout the set. Twenty
      four and 15 athletes, respectively, performed a set of 10 repetitions in both the
      bench throw (BT P60) and jump squat exercise (JS P60) with a resistance of 60 kg.
      For both exercises, power output was highest on either the second (JS P60) or the
      third repetition (BT P60) and was then maintained until the fifth repetition.
      Significant declines in power output occurred from the sixth repetition onwards
      until the 10th repetition (11.2% for BT P60 and 5% for JS P60 by the 10th
      repetition). These findings suggest that athletes attempting to increase maximal
      power limit their repetitions to 2 to 5 when using resistances of 35 to 45% 1RM
      in these exercises.

PMID- 18076275
TI  - Effect of duration and exogenous carbohydrate on gross efficiency during cycling.
AB  - The purpose of this investigation was to determine the effects of 2.5 hours of
      cycling with and without carbohydrate supplementation on gross efficiency (GE).
      Trained cyclists (N = 15) were tested for V(.-)O2max (53.6 + 2.2 ml x kg(-1) x
      min(-1)) and lactate threshold during incremental tests to exhaustion. On 2
      separate visits, cyclists performed 2.5 hours of cycling on an indoor trainer. A
      carbohydrate (C) or placebo (P) beverage was randomly provided and
      counterbalanced for each of the trials. Gross efficiency, cycling economy, power
      output, V(.-)O2, lactate, and blood glucose were measured every 20 minutes during
      the 2.5-hour ride. Muscle glycogen was measured immediately before and after the
      ride from the vastus lateralis. Results indicated that power output and V(.-)O2
      decreased over time (p < 0.05) but were not different between trials. Relative GE
      and cycling economy during C were greater than P at 40 and 150 minutes (p <
      0.05). Blood glucose significantly decreased in P and was lower than C at all
      time points (p < 0.05). Respiratory exchange ratio decreased over time in both
      trials, with a significant treatment effect at 40 and 150 minutes (p < 0.05).
      Muscle glycogen decreased by 65% during both conditions (p < 0.05) but
      demonstrated no treatment effect. We conclude that carbohydrate supplementation
      during 2.5 hours of cycling attenuated the decrease in GE possibly by maintaining
      blood glucose levels. This suggests that the positive effect of carbohydrate
      supplementation on endurance performance may be through the maintenance of
      metabolic efficiency.

PMID- 18076276
TI  - Relationship of jumping and agility performance in female volleyball athletes.
AB  - Court sports often require more frequent changes of direction (COD) than field
      sports. Most court sports require 180 degrees turns over a small distance, so COD
      in such sports might be best evaluated with an agility test involving short
      sprints and sharp turns. The purposes of this study were to (a) quantify vertical
      and horizontal force during a COD task, (b) identify possible predictors of court
      sport-specific agility performance, and (c) examine performance difference
      between National Collegiate Athletic Association Division I, II, and III
      athletes. Twenty-nine collegiate female volleyball players completed a novel
      agility test, countermovement (CM) and drop jump tests, and an isometric leg
      extensor test. The number of athletes by division was as follows: I (n = 9), II
      (n = 11), and III (n = 9). The agility test consisted of 4 5-meter sprints with 3
      180 degrees turns, including 1 on a multiaxial force platform so that the kinetic
      properties of the COD could be identified. One-way analysis of variance revealed
      that Division I athletes had significantly greater countermovement jump heights
      than Division III, and the effect size comparisons (Cohen's d) showed large
      magnitude differences between Division I and both Divisions II and III for jump
      height. No other differences in performance variables were noted between
      divisions, although effect sizes reached moderate values for some comparisons.
      Regression analysis revealed that CM displacement was a significant predictor of
      agility performance, explaining approximately 34% of the variance. Vertical force
      was found to account for much of the total force exerted during the contact phase
      of the COD task, suggesting that performance in the vertical domain may limit the
      COD task used herein. This study indicates that individuals with greater CM
      performance also have quicker agility times and suggests that training
      predominantly in the vertical domain may also yield improvements in certain types
      of agility performance. This may hold true even if such agility performance
      requires a horizontal component.

PMID- 18076277
TI  - Energy expenditure and influence of physiologic factors during marathon running.
AB  - This study examined energy expenditure and physiologic determinants for marathon
      performance in recreational runners. Twenty recreational marathon runners
      participated (10 males aged 41 +/- 11.3 years, 10 females aged 42.7 +/- 11.7
      years). Each subject completed a V(.-)O2max and a 1-hour treadmill run at recent
      marathon pace, and body composition was indirectly determined via dual energy X
      ray absorptiometry. The male runners exhibited higher V(.-)O2max (ml x kg(-1) x
      min(-1)) values (52.6 +/- 5.5) than their female counterparts (41.9 +/- 6.6),
      although ventilatory threshold (T-vent) values were similar between groups
      (males: 76.2 +/- 6.1 % of V(.-)O2max, females: 75.1 +/- 5.1%). The male runners
      expended more energy (2,792 +/- 235 kcal) for their most recent marathon as
      calculated from the 1-hour treadmill run at marathon pace than the female runners
      (2,436 +/- 297 kcal). Body composition parameters correlated moderately to highly
      (r ranging from 0.50 to 0.87) with marathon run time. Also, V(.-)O2max (r = 
      0.73) and ventilatory threshold (r = -0.73) moderately correlated with marathon
      run time. As a group, the participants ran near their ventilatory threshold for
      their most recent marathon (r = 0.74). These results indicate the influence of
      body size on marathon run performance. In general, the larger male and female
      runners ran slower and expended more kilocalories than smaller runners.
      Regardless of marathon finishing time, the runners maintained a pace near their T
      vent, and as T-vent or V(.-)O2max increased, marathon performance time decreased.

PMID- 18076278
TI  - Age-related decline in handgrip strength differs according to gender.
AB  - It is well-established that at old age there is a significant decline in muscle
      strength. Reference values for muscle strength might be useful for assessment of
      muscle impairment and of physiological adaptations. However, it is still unclear
      whether gender affects the rate of decline. Therefore, the aim of this study is
      to investigate the effect of gender and age on handgrip strength and to establish
      reference values for this variable. Reviewing medical charts collected from 1994
      to 2005, a convenience sample of 2,648 subjects (1,787 men and 861 women), aged
      between 18 and 90 years, was obtained. Our results show higher handgrip strength
      for men compared with women (36.8 +/- 0.20 vs. 21.0 +/- 0.18 kg; p < 0.001). The
      regression analysis with a quadratic model shows that aging accounts for 30% of
      the variance in handgrip strength (r(2) = 0.30; p < 0.001) in men and 28% (r(2) =
      0.28; p < 0.001) in women. In addition, the bent linear regression with multiple
      regressors show that a faster decline in handgrip strength occurs at the age of
      30 years for men and 50 years for women. We conclude that handgrip strength
      decline with age differs between genders, making useful the existence of distinct
      male and female normative age group data.

PMID- 18076279
TI  - A prospective study of red and processed meat intake in relation to cancer risk.
AB  - BACKGROUND: Red meat and processed meat have been associated with carcinogenesis
      at several anatomic sites, but no prospective study has examined meat intake in
      relation to a range of malignancies. We investigated whether red or processed
      meat intake increases cancer risk at a variety of sites. METHODS AND FINDINGS:
      The National Institutes of Health (NIH)-AARP (formerly the American Association
      for Retired Persons) Diet and Health Study is a cohort of approximately 500,000
      people aged 50-71 y at baseline (1995-1996). Meat intake was estimated from a
      food frequency questionnaire administered at baseline. Cox proportional hazards
      regression was used to estimate hazard ratios and 95% confidence intervals within
      quintiles of red and processed meat intake. During up to 8.2 y of follow-up,
      53,396 incident cancers were ascertained. Statistically significant elevated
      risks (ranging from 20% to 60%) were evident for esophageal, colorectal, liver,
      and lung cancer, comparing individuals in the highest with those in the lowest
      quintile of red meat intake. Furthermore, individuals in the highest quintile of
      processed meat intake had a 20% elevated risk for colorectal and a 16% elevated
      risk for lung cancer. CONCLUSIONS: Both red and processed meat intakes were
      positively associated with cancers of the colorectum and lung; furthermore, red
      meat intake was associated with an elevated risk for cancers of the esophagus and
      liver.

PMID- 18076280
TI  - The consumption of khat and other drugs in Somali combatants: a cross-sectional
      study.
AB  - BACKGROUND: For more than a decade, most parts of Somalia have not been under the
      control of any type of government. This "failure of state" is complete in the
      central and southern regions and most apparent in Mogadishu, which had been for a
      long period in the hands of warlords deploying their private militias in a battle
      for resources. In contrast, the northern part of Somalia has had relatively
      stable control under regional administrations, which are, however, not
      internationally recognized. The present study provides information about drug
      abuse among active security personnel and militia with an emphasis on regional
      differences in relation to the lack of central governmental control-to our
      knowledge the first account on this topic. METHODS AND FINDINGS: Trained local
      interviewers conducted a total of 8,723 interviews of armed personnel in seven
      convenience samples in different regions of Somalia; 587 (6.3%) respondents
      discontinued the interview and 12 (0.001%) were excluded for other reasons. We
      assessed basic sociodemographic information, self-reported khat use, and how
      respondents perceived the use of khat, cannabis (which includes both hashish and
      marijuana), psychoactive tablets (e.g., benzodiazepines), alcohol, solvents, and
      hemp seeds in their units. The cautious interpretation of our data suggest that
      sociodemographic characteristics and drug use among military personnel differ
      substantially between northern and southern/central Somalia. In total, 36.4% (99%
      confidence interval [CI] 19.3%-57.7%) of respondents reported khat use in the
      week before the interview, whereas in some regions of southern/central Somalia
      khat use, especially excessive use, was reported more frequently. Self-reported
      khat use differed substantially from the perceived use in units. According to the
      perception of respondents, the most frequent form of drug use is khat chewing (on
      average, 70.1% in previous week, 99% CI 63.6%-76.5%), followed by smoking
      cannabis (10.7%, 99% CI 0%-30.4%), ingesting psychoactive tablets (8.5%, 99% CI
      0%-24.4%), drinking alcohol (5.3%, 99% CI 0%-13.8%), inhaling solvents (1.8%, 99%
      CI 0%-5.1%), and eating hemp seeds (0.6%, 99% CI 0%-2.0%). Perceived use of khat
      differs little between northern and southern Somalia, but perceived use of other
      drugs reaches alarmingly high levels in some regions of the south, especially
      related to smoking cannabis and using psychoactive tablets. CONCLUSIONS: Our data
      suggest that drug use has quantitatively and qualitatively changed over the
      course of conflicts in southern Somalia, as current patterns are in contrast to
      traditional use. Although future studies using random sampling methods need to
      confirm our results, we hypothesize that drug-related problems of armed staff and
      other vulnerable groups in southern Somalia has reached proportions formerly
      unknown to the country, especially as we believe that any biases in our data
      would lead to an underestimation of actual drug use. We recommend that future
      disarmament, demobilization, and reintegration (DDR) programs need to be prepared
      to deal with significant drug-related problems in Somalia.

PMID- 18076281
TI  - Meat consumption and cancer risk.

PMID- 18076282
TI  - Clustered environments and randomized genes: a fundamental distinction between
      conventional and genetic epidemiology.
AB  - BACKGROUND: In conventional epidemiology confounding of the exposure of interest
      with lifestyle or socioeconomic factors, and reverse causation whereby disease
      status influences exposure rather than vice versa, may invalidate causal
      interpretations of observed associations. Conversely, genetic variants should not
      be related to the confounding factors that distort associations in conventional
      observational epidemiological studies. Furthermore, disease onset will not
      influence genotype. Therefore, it has been suggested that genetic variants that
      are known to be associated with a modifiable (nongenetic) risk factor can be used
      to help determine the causal effect of this modifiable risk factor on disease
      outcomes. This approach, mendelian randomization, is increasingly being applied
      within epidemiological studies. However, there is debate about the underlying
      premise that associations between genotypes and disease outcomes are not
      confounded by other risk factors. We examined the extent to which genetic
      variants, on the one hand, and nongenetic environmental exposures or phenotypic
      characteristics on the other, tend to be associated with each other, to assess
      the degree of confounding that would exist in conventional epidemiological
      studies compared with mendelian randomization studies. METHODS AND FINDINGS: We
      estimated pairwise correlations between nongenetic baseline variables and genetic
      variables in a cross-sectional study comparing the number of correlations that
      were statistically significant at the 5%, 1%, and 0.01% level (alpha = 0.05,
      0.01, and 0.0001, respectively) with the number expected by chance if all
      variables were in fact uncorrelated, using a two-sided binomial exact test. We
      demonstrate that behavioural, socioeconomic, and physiological factors are
      strongly interrelated, with 45% of all possible pairwise associations between 96
      nongenetic characteristics (n = 4,560 correlations) being significant at the p <
      0.01 level (the ratio of observed to expected significant associations was 45; p
      value for difference between observed and expected < 0.000001). Similar findings
      were observed for other levels of significance. In contrast, genetic variants
      showed no greater association with each other, or with the 96 behavioural,
      socioeconomic, and physiological factors, than would be expected by chance.
      CONCLUSIONS: These data illustrate why observational studies have produced
      misleading claims regarding potentially causal factors for disease. The findings
      demonstrate the potential power of a methodology that utilizes genetic variants
      as indicators of exposure level when studying environmentally modifiable risk
      factors.

PMID- 18076283
TI  - Drug consumption in conflict zones in Somalia.

PMID- 18076284
TI  - Improving science education for sustainable development.

PMID- 18076285
TI  - Mapping meiotic single-strand DNA reveals a new landscape of DNA double-strand
      breaks in Saccharomyces cerevisiae.
AB  - DNA double-strand breaks (DSBs), which are formed by the Spo11 protein, initiate
      meiotic recombination. Previous DSB-mapping studies have used rad50S or sae2Delta
      mutants, which are defective in break processing, to accumulate Spo11-linked
      DSBs, and report large (> or = 50 kb) "DSB-hot" regions that are separated by
      "DSB-cold" domains of similar size. Substantial recombination occurs in some DSB
      cold regions, suggesting that DSB patterns are not normal in rad50S or sae2Delta
      mutants. We therefore developed a novel method to map genome-wide, single-strand
      DNA (ssDNA)-associated DSBs that accumulate in processing-capable, repair
      defective dmc1Delta and dmc1Delta rad51Delta mutants. DSBs were observed at known
      hot spots, but also in most previously identified "DSB-cold" regions, including
      near centromeres and telomeres. Although approximately 40% of the genome is DSB
      cold in rad50S mutants, analysis of meiotic ssDNA from dmc1Delta shows that most
      of these regions have substantial DSB activity. Southern blot assays of DSBs in
      selected regions in dmc1Delta, rad50S, and wild-type cells confirm these
      findings. Thus, DSBs are distributed much more uniformly than was previously
      believed. Comparisons of DSB signals in dmc1, dmc1 rad51, and dmc1 spo11 mutant
      strains identify Dmc1 as a critical strand-exchange activity genome-wide, and
      confirm previous conclusions that Spo11-induced lesions initiate all meiotic
      recombination.

PMID- 18076286
TI  - The foxa2 gene controls the birth and spontaneous degeneration of dopamine
      neurons in old age.
AB  - Parkinson disease affects more than 1% of the population over 60 y old. The
      dominant models for Parkinson disease are based on the use of chemical toxins to
      kill dopamine neurons, but do not address the risk factors that normally increase
      with age. Forkhead transcription factors are critical regulators of survival and
      longevity. The forkhead transcription factor, foxa2, is specifically expressed in
      adult dopamine neurons and their precursors in the medial floor plate. Gain- and
      loss-of-function experiments show this gene, foxa2, is required to generate
      dopamine neurons during fetal development and from embryonic stem cells. Mice
      carrying only one copy of the foxa2 gene show abnormalities in motor behavior in
      old age and an associated progressive loss of dopamine neurons. Manipulating
      forkhead function may regulate both the birth of dopamine neurons and their
      spontaneous death, two major goals of regenerative medicine.

PMID- 18076287
TI  - Dosage compensation in the mouse balances up-regulation and silencing of X-linked
      genes.
AB  - Dosage compensation in mammals involves silencing of one X chromosome in XX
      females and requires expression, in cis, of Xist RNA. The X to be inactivated is
      randomly chosen in cells of the inner cell mass (ICM) at the blastocyst stage of
      development. Embryonic stem (ES) cells derived from the ICM of female mice have
      two active X chromosomes, one of which is inactivated as the cells differentiate
      in culture, providing a powerful model system to study the dynamics of X
      inactivation. Using microarrays to assay expression of X-linked genes in
      undifferentiated female and male mouse ES cells, we detect global up-regulation
      of expression (1.4- to 1.6-fold) from the active X chromosomes, relative to
      autosomes. We show a similar up-regulation in ICM from male blastocysts grown in
      culture. In male ES cells, up-regulation reaches 2-fold after 2-3 weeks of
      differentiation, thereby balancing expression between the single X and the
      diploid autosomes. We show that silencing of X-linked genes in female ES cells
      occurs on a gene-by-gene basis throughout differentiation, with some genes
      inactivating early, others late, and some escaping altogether. Surprisingly, by
      allele-specific analysis in hybrid ES cells, we also identified a subgroup of
      genes that are silenced in undifferentiated cells. We propose that X-linked genes
      are silenced in female ES cells by spreading of Xist RNA through the X chromosome
      territory as the cells differentiate, with silencing times for individual genes
      dependent on their proximity to the Xist locus.

PMID- 18076288
TI  - Painful digital fissures.

PMID- 18076290
TI  - Changes in vitamin status of Indian Antarctic expeditioners during a one-month
      stay in Austral Summer.
AB  - OBJECTIVE: Antarctic expeditioners face extremes of environmental conditions
      along with isolation which affect normal human activity at a polar station. Diets
      of polar expeditioners consist of products that have been kept in storage for
      more than a year. Processing and preservation adversely affect the nutritive
      value of the food products, especially water-soluble vitamins. This study was
      conducted to determine water-soluble vitamin status of Antarctic expeditioners
      consuming processed canned food. METHODS: Twenty-two healthy male volunteers age
      26 to 56 years (39.5+/-8.5, mean+/-SD) participated in the study. The study was
      conducted in 3 phases: at Goa, India (phase I), 48 hours after arriving in
      Antarctica (phase II) and after 1 month in Antarctica (phase III). Water-soluble
      vitamin status in erythrocytes was assessed at each phase with evaluation of
      riboflavin, thiamine, and pyridoxine status. Urinary N-methyl nicotinamide and
      methylmalonic acid (MMA) levels were measured to assess niacin and vitamin B(12)
      status. Blood plasma assays were used to assess ascorbic acid status. RESULTS: No
      significant changes in riboflavin, thiamine, and pyridoxine status in
      erythrocytes and urinary excretion levels were observed after 1 month in
      Antarctica. Vitamin C levels decreased significantly (P<.001) after 1 month in
      Antarctica compared with basal values (1.31+/-0.076 mg/dL during phase I to
      0.81+/-0.063 mg/dL during phase III). However, these levels were still within the
      normal reference range. CONCLUSION: This study found no water-soluble vitamin
      deficiencies in participants consuming processed and canned food after 1 month in
      Antarctica.

PMID- 18076291
TI  - Avalanche safety practices in Utah.
AB  - OBJECTIVE: Avalanche fatalities occur on a yearly basis in Utah. The purpose of
      this study was to assess avalanche safety practices of different backcountry
      users in Utah and to identify groups that can be targeted for avalanche safety
      education. METHODS: We surveyed 353 winter backcountry users to determine the
      percentage of participants in each group who were traveling with one or more
      partners; the percentage who were carrying avalanche transceivers, shovels,
      probes, or AvaLungs; and the percentage who had taken an avalanche safety course.
      A measure of minimum safe practice was defined as 1) traveling with a partner, 2)
      carrying an avalanche transceiver, and 3) carrying a shovel. Participants in this
      study were backcountry skiers, snowboarders, snowshoers, snowmobilers, and out-of
      bounds resort skiers/snowboarders traveling in the Wasatch and Uinta Mountains of
      Utah during the winter of 2005-06. RESULTS: The percentage of backcountry
      recreationists traveling with one or more partners was not significantly
      different (P=.0658) among backcountry skiers, snowboarders, snowshoers,
      snowmobilers, and out-of-bounds resort skiers/snowboarders. These groups did,
      however, differ in the percentage who carried avalanche transceivers (P<.0001),
      shovels (P<.0001), probes (P<.0001), and AvaLungs (P=.0020), as well as in the
      percentage who had taken an avalanche safety course (P<.0001) and the percentage
      who were carrying out minimum safe practices (P<.0001). Backcountry skiers showed
      the highest level of avalanche preparedness, with 98% carrying avalanche
      transceivers, 98% carrying shovels, 77% carrying probes, 86% having taken an
      avalanche safety course, and 88% carrying out minimum safe practices. Out of
      bounds snowboarders were the least prepared with 9% carrying avalanche
      transceivers, 9% carrying shovels, 7% carrying probes, 33% having taken an
      avalanche safety course, and 2% carrying out minimum safe practices. CONCLUSIONS:
      There are significant differences in the avalanche safety practices of the
      various groups of backcountry travelers in Utah. Backcountry skiers and
      snowboarders were the most prepared, while snowmobilers, snowshoers, and out-of
      bounds skiers/snowboarders were relatively less prepared.

PMID- 18076292
TI  - Ginkgo biloba decreases acute mountain sickness in people ascending to high
      altitude at Ollague (3696 m) in northern Chile.
AB  - OBJECTIVE: To determine the prophylactic effect of Ginkgo biloba (doses 80 mg/12
      h, 24 h before high-altitude ascension and with continued treatment) in
      preventing acute mountain sickness (AMS) at 3696 m in participants without high
      altitude experience. METHODS: Thirty-six participants who reside at sea level
      were transported to an altitude of 3696 m (Ollague). The participants were
      divided into 3 groups and received G biloba (n=12) 80 mg/12 h, acetazolamide
      (n=12) 250 mg/12 h, or placebo (n=12) 24 hours before ascending and during their
      3-day stay at high altitude. The Lake Louise Questionnaire constituted the
      primary outcome measurement at sea level and at 3696 m. A Lake Louise Self-Report
      Score greater than 3 was indicative of AMS. Oxygen saturation, heart rate, and
      arterial pressure were taken with each evaluation for AMS. RESULTS: A significant
      reduction in AMS was observed in the group that received G biloba (0%, P<.05)
      comparison with the groups receiving acetazolamide (36%, P<.05) or placebo (54%).
      No difference was observed in arterial oxygen saturation in the G biloba (92+/-2)
      vs the acetazolamide (89+/-2) groups. However, a marked increased saturation in
      arterial oxygen was seen in comparison with the placebo group (84+/-3, P<.05). No
      statistically significant differences were observed in mean arterial pressure or
      heart rate. CONCLUSIONS: This study provides evidence supporting the use of G
      biloba in the prevention of AMS, demonstrating that 24 hours of pretreatment with
      G biloba and subsequent maintenance during exposure to high altitude are
      sufficient to reduce the incidence of AMS in participants with no previous high
      altitude experience.

PMID- 18076293
TI  - Injuries in bouldering: a prospective study.
AB  - OBJECTIVE: Bouldering is a type of rock climbing in which the climber ascends
      small boulders with pads and spotters in lieu of ropes, with an emphasis on
      ascending the most difficult surface possible. We sought to investigate the
      prevalence and incidence of injuries, and we hypothesized boulderers who enlisted
      preventative measures and those who bouldered indoors would have fewer injuries.
      METHODS This cross-sectional cohort study assessed incidence and pattern of
      injury among indoor and outdoor boulderers over 1 year. RESULTS: Spotting other
      boulderers resulted in few injuries, but both climbing and falling were
      associated with diffuse injuries. Finger and ankle injuries were common.
      Traditional preventative measures were ineffective, and there were few
      differences between indoor and outdoor boulderers. CONCLUSIONS: Bouldering
      outdoors has an increased risk of injury to the fingers. Preventative measures
      appear largely ineffective in reducing the number of injuries in both cohorts.

PMID- 18076294
TI  - Snakebite injuries treated in United States emergency departments, 2001-2004.
AB  - OBJECTIVE: Venomous and nonvenomous snakes are found throughout most of the
      United States. While the literature on treatment is robust, there is not a
      current national epidemiologic profile of snakebite injuries in the United
      States. National estimates of such injuries treated in emergency departments
      (EDs) are presented along with characteristics of the affected population.
      METHODS: Data on snakebite injuries were abstracted from the National Electronic
      Injury Surveillance System-All Injury Program (2001-04). Variables included age,
      gender, body part affected, cause, disposition, and treatment date. When
      available, location, intentionality of the interaction, and snake species were
      coded based on narrative comments. Estimates were weighted and analyzed with SPSS
      Complex Samples. RESULTS: An estimated 9873 snakebites were treated in US EDs
      each year between 2001 and 2004. Males were more frequently seen in the ED for
      snakebites than were females (males: 72.0% [95% confidence interval (CI), 68.0
      75.7]; females: 28.0% [95% CI, 24.3-32.0]). Approximately 32% of patients were
      known to be bitten by venomous species. Overall, more than one quarter of
      patients were hospitalized (27.9% [95% CI, 15.9-44.2]), although 58.9% of
      patients with known venomous bites were hospitalized (95% CI, 41.5-74.3).
      CONCLUSIONS: While they are rare events, snakebites cause nearly 10,000 visits to
      EDs for treatment every year. Epidemiologic data regarding snakebites provide
      practicing physicians with an understanding of the population affected and can
      help guide public health practitioners in their prevention efforts.

PMID- 18076295
TI  - Animal-caused fatalities in New Mexico, 1993-2004.
AB  - OBJECTIVE: To evaluate animal-caused fatalities in New Mexico using data
      collected during medicolegal death investigations, including toxicology, survival
      interval, and circumstances. METHODS: A retrospective review of the computerized
      database and hard copies of files from a centralized, statewide medical
      examiner's office, excluding deaths due to zoonotic diseases and motor vehicle
      collisions involving animals. RESULTS: Between 1993 and 2004, 63 deaths caused by
      animals were reported in New Mexico. The majority of decedents were male (46/63,
      73%) and non-Hispanic white (33/63, 52%). Horses were the most commonly
      implicated animals, with 43 (68%) deaths due to a person being thrown from,
      crushed, dragged, or kicked by a horse. Cattle caused 9 deaths (14%), dogs caused
      3 (5%), and venomous animals caused 3, whereas a bear was responsible for 1
      death. Ten decedents (16%) had alcohol present at the time of death, and 8 would
      have been over the legal blood alcohol concentration for driving (0.08%). Ten
      deaths (16%) were work-related and included deaths of jockeys and ranch workers.
      The majority of deaths (42/63, 67%) occurred in remote locations, potentially
      delaying access to treatment. Survival intervals ranged from 1 day to 33 years.
      CONCLUSIONS: Whereas both human and animal behavior can be difficult to predict,
      a review of animal-caused fatalities investigated by a medical examiner revealed
      that in many cases, deaths could have been prevented by either the use of
      protective gear or alterations in human behavior.

PMID- 18076297
TI  - New-onset anxiety disorders at high altitude.
AB  - OBJECTIVE: Studies on the neurologic effects of high-altitude travel have focused
      on psychometric and cognitive testing and the long-term effects of hypoxia on
      memory and cognition. Few authors have discussed overt clinical psychiatric
      illness during high-altitude travel, and those few have focused on patients with
      preexisting psychiatric diagnoses. We describe a series of patients with new
      onset anxiety disorders at high altitude treated at the Himalayan Rescue
      Association (HRA) clinic in Pheriche, Nepal (4240 m) in the spring season of
      2006. METHODS: We report on all 6 cases of anxiety-related illness diagnosed at
      the HRA Pheriche Clinic during the spring season, 2006. Three cases, representing
      the 3 discrete types of illness we encountered, are described in detail. RESULTS:
      Six of 76 foreign patients and none of the 224 Nepalis seen during the season had
      anxiety-related primary diagnoses. None of the 6 patients had a history of
      psychiatric disorders or anxiety-related problems at low altitude. Three of the 6
      patients were seen after hours, and all 6 required multiple visits. We describe 3
      types of anxiety-related disorders: limited-symptom panic attacks induced by
      nocturnal periodic breathing, excessive health-related anxiety, and excessive
      emotionality. CONCLUSIONS: Anxiety-related illness requires significant use of
      medical resources by high-altitude travelers. Further research is needed to
      define the epidemiology of anxiety-related disorders at high altitude, to
      quantify the contributions of various etiologic factors, and to identify safe,
      effective treatments.

PMID- 18076298
TI  - A case of an Alpinist with a patent foramen ovale and high-altitude pulmonary
      edema at moderate altitude.

PMID- 18076299
TI  - A reference correction.

PMID- 18076300
TI  - Cause of death in avalanche fatalities.
AB  - OBJECTIVE: Avalanches pose a life-threatening risk to participants of outdoor
      winter activities. Determining the causes of death in avalanche fatalities can
      aid rescue and resuscitation strategies and hopefully improve survival. METHODS:
      The study population included all avalanche fatalities in Utah from the 1989-90
      to 2005-06 winter seasons. The Utah Avalanche Center and Medical Examiner records
      were reviewed to identify accident circumstances, autopsy findings, and causes of
      death. RESULTS: Fifty-six avalanche deaths were identified during the study
      period. Most deaths occurred while participating in recreational backcountry
      activities; 85.7% of deaths were due to asphyxiation, 8.9% were due to a
      combination of asphyxiation and trauma, and 5.4% were due to trauma alone. Head
      injuries were frequent in those killed solely by trauma. CONCLUSIONS: Most
      avalanche deaths in Utah result from asphyxia. Therefore, most victims are alive
      in the postavalanche period and have the potential for live recovery. Rescue
      strategies that employ rapid recovery as well as techniques that prolong survival
      while buried provide the best means of improving outcome.

PMID- 18076301
TI  - Medical incidents and evacuations on wilderness expeditions.
AB  - OBJECTIVE: Expedition activities such as mountaineering, rock climbing, river
      running, sea kayaking, and canoeing all involve an element of risk. Organizations
      that provide group wilderness and adventure experiences are responsible for
      managing the risk of their courses. The leaders and medical providers of these
      trips must therefore be prepared to anticipate and manage medical problems that
      may arise. The aim of this study is to provide the medical community with a
      better understanding of the specific injuries and illnesses that occur on
      wilderness expeditions. METHODS: A retrospective descriptive study was done
      examining the medical incidents that occurred on wilderness-based courses during
      the 3-year period from September 1, 2002, through August 31, 2005. Participants
      and staff of the National Outdoor Leadership School (NOLS) served as the study
      population. RESULTS: Injuries occurred at a rate of 1.18 per 1000 program days,
      and illnesses at a rate of 1.08 per 1000 program days. There were no fatalities
      during the time period. Athletic injuries (sprains, strains) and gastrointestinal
      illnesses were the most common medical incidents. Hypothermia, seizures,
      appendicitis, heat stroke, and pregnancy occurred but with low frequency.
      Fractures, dental emergencies, tick fever, athletic injuries, and nonspecific
      body pains were the conditions most frequently requiring evacuation. CONCLUSIONS:
      The rate of medical incidents on NOLS courses declined during the 1990s and has
      remained relatively steady apart from a slight increase in 2004 and 2005.
      Athletic injuries continue to be a difficulty, as they frequently result in
      evacuation even though their ultimate outcome is usually benign. Evacuation
      decisions should be made considering both the potential severity of the medical
      condition as well as patient comfort. Wilderness medical personnel must be
      familiar with a diverse range of medical conditions in order to provide optimal
      care.

PMID- 18076302
TI  - Pulmonary artery pressure in healthy subjects at 4250 m measured by Doppler
      echocardiography.
AB  - OBJECTIVE: Acute hypoxia causes vasoconstriction in the pulmonary arteries. This
      hypoxic pulmonary vasoconstriction (HPV) has been reported to be common in
      subjects exposed to high altitude. In the past, it has been difficult to directly
      measure this HPV because of the invasive nature of tests, but the recent
      availability of portable color flow Doppler ultrasound has enabled measurements
      of pulmonary artery systolic pressure (PASP) in the field. We set out to study
      the feasibility of this method to detect changes related to HPV at 4250 m. We
      hypothesized that significant changes in the cardiopulmonary circulation are seen
      at high altitude and are detectable with Doppler echocardiography. In addition,
      we hypothesized that detected changes are related to the syndrome of acute
      mountain sickness (AMS) and could be reversed using 100% oxygen. METHODS: Over a
      10-week period in the spring of 1998, 56 healthy lowlanders not normally residing
      at altitude were studied while visiting 4250 m in Nepal having walked from 2774
      m. This was a cross-sectional observational study conducted by a single
      experienced observer at high altitude, using transthoracic color flow continuous
      wave Doppler echocardiography. Subjects were initially assessed for significant
      tricuspid regurgitation (TR) to measure PASP. After estimating PASP under ambient
      conditions at altitude, oxygen was delivered and PASP remeasured. RESULTS: Of 56
      subjects, 36 had Doppler signals appropriate for estimation of pulmonary artery
      systolic pressure. In these 36, a wide range of PASP was observed (mean 25 mm Hg,
      range 18-36 mm Hg), but none fell outside of the normal range. After oxygen
      administration, PASP was reduced (from mean 25 mm Hg to mean 18 mm Hg, P<.0001)
      suggesting that a degree of hypoxic pulmonary vasoconstriction was present. No
      subjects in the study group reported clinical AMS. CONCLUSIONS: We found PASP at
      4250 m to be within the normal range but higher than would be expected at sea
      level; however, unlike previous reports, we found such increases to be mild and
      reversible with oxygen. In addition, the observed incidence of AMS was low when
      compared with earlier studies, perhaps related to adequate acclimatization.

PMID- 18076303
TI  - Sequence analysis of the regions flanking terminal repeats of the genome of umava
      isolate of murine gammaherpesvirus.
AB  - The umava isolate of murine gammaherpesvirus (MHV-umava) slightly differs from
      Murine gammaherpesvirus 68 (MHV-68) and two other isolates of murine
      gammaherpesvirus (MHV), MHV-76 and MHV-72 in some biological properties. To
      identify the region(s) in the MHV-umava genome responsible for this phenomenon,
      we compared the sequences flanking terminal repeats (TRs) of the MHV-umava genome
      with those of MHV-68, MHV-76 and MHV-72. Restriction and sequence analyses
      revealed in MHV-umava as compared to MHV-68 approximately 9.3 kbp deletion at the
      left end of the genome and approximately 1.5 kbp deletion at the right end of the
      genome. While the approximately 9.3 kbp deletion was similar to that in MHV-76,
      the approximately 1.5 kbp deletion was unique for MHV-umava.

PMID- 18076304
TI  - Spike protein region (aa 636789) of porcine epidemic diarrhea virus is essential
      for induction of neutralizing antibodies.
AB  - To analyze antigenic structure of the spike (S) protein of Porcine epidemic
      diarrhea virus (PEDV), the gene encoding its major immunodominant region S1 was
      amplified by PCR. We prepared four truncated S1 proteins spanning the entire S1
      domain fused to GST protein. To identify the most important antigenic region of
      S1, the truncated S1-GST fusion proteins were examined for their ability to react
      with immune serum against PEDV and to elicit the formation of neutralization
      antibodies in immunized animals. We found that the region of S1 signed as S1D (aa
      636789) was able to react with PEDV antiserum and to elicit formation of
      neutralization antibodies in mice. Moreover, the immune serum against S1D showed
      the binding ability to the native S protein of PEDV.

PMID- 18076305
TI  - Expression of the barley yellow dwarf virus-GAV movement protein and its
      detection in the infected and transgenic plants.
AB  - Movement proteins (MPs) that facilitate virus movement in the plants were
      identified in a number of plant viruses. In this study, full-length MP gene of
      the Chinese isolate Barley yellow dwarf virus-GAV (BYDV-GAV) was cloned and
      expressed in Escherichia coli. About 32% of the expressed MP was soluble
      providing the concentration of isopropyl-beta-D-galactopyranoside (IPTG), time of
      the induction, temperature and shaking speed were optimized. The soluble MP was
      purified using nickel-affinity column. Immune serum prepared against purified MP
      was used for the detection of MP in the BYDV-GAV infected leaves of oat and in
      the leaves of transgenic wheat plants expressing the full-length and truncated MP
      gene.

PMID- 18076306
TI  - DNA priming and killed virus boosting vaccination strategy can augment the immune
      response to pseudorabies virus.
AB  - The immune efficacy of DNA vaccines containing three plasmids encoding gB, gC,
      and gD glycoproteins (Mix DNA) of Pseudorabies virus (PRV) or the plasmid for gC
      only (gC DNA), killed virus (KV) vaccine or combination of gC DNA, Mix DNA and KV
      vaccines was evaluated in mice using primeboost strategy. The mice vaccinated
      twice with Mix DNA, and once with KV generated higher levels of gCspecific and
      virus neutralization (VN) antibodies and a stronger cellular immune response than
      the mice vaccinated three times with the Mix DNA vaccine only. The highest level
      of VN antibodies were detected in mice vaccinated twice with KV vaccines alone or
      with combination of DNA and KV vaccines. The challenge of vaccinated mice with
      the lethal dose of PRV showed that the complete protection against PRV was
      achieved in the group of mice immunized with the DNA and KV vaccines combined.
      The results suggested that DNA priming followed by KV vaccine boosting could
      enhance the antibody response and cellular immunity against PRV infection in
      mice.

PMID- 18076307
TI  - Intratracheal inoculation of severe acute respiratory syndrome coronavirus in
      monkeys Macaca rhesus.
AB  - An animal model for infection with Severe acute respiratory syndrome coronavirus
      (SARSCoV) was evaluated in monkeys Macaca rhesus. The monkeys were inoculated
      into the trachea with NS-I strain of SARS-CoV and the clinical manifestation of
      the illness was monitored. The clinical samples collected from infected monkeys
      were examined by immumnofluorescence assay (IFA), pathological inspection, RTPCR,
      and by virus isolation. The infected animals demonstrated mild clinical symptoms
      including fever. Two of the six infected monkeys developed fever (1.5 above the
      level before challenge) on the day 10 post inoculation (p.i.). Although the
      severe clinical symptoms or mortality were not observed, the virological and
      histopathological evidences of the illness were evident. The specimens collected
      from the infected animals showed the presence of SARS-CoV detected by RT-PCR,
      IFA, and by virus isolation. From the organs examined postmortem, a major
      pathological change was observed in the lungs. The walls of the alveoli were
      thicker, infiltrated with inflammation cells and an exudative fluid was found in
      the alveolar spaces. In addition, some alveolar spaces showed hyaline membrane
      lining. The results showed that the monkeys infected with SARS-CoV developed the
      typical SARS according to clinical, virological, and pathological findings.

PMID- 18076308
TI  - Replication of Japanese encephalitis virus in mouse brain induces alterations in
      lymphocyte response.
AB  - The experimental model using intracerebral (i.c.) challenge was employed in many
      studies evaluating the protection against disease induced by Japanese
      encephalitis virus (JEV). We investigated alterations in peripheral lymphocyte
      response caused by i.c. infection of mice with JEV. Splenocytes from the i.c.
      infected mice showed suppressed proliferative response to concanavalin A (con A)
      and anti-CD3 antibody stimulation. At the same time, the expression of CD25 (IL
      2R) and production of IL-2 was inhibited. Addition of anti-CD28 antibody restored
      the decreased anti-CD3 antibody-mediated proliferation in the splenocytes.
      Moreover, the number of con A-stimulated cells secreting IL-4 was significantly
      reduced in splenocytes from i.c.-infected mice. These studies suggested that the
      i.c. infection with JEV might involve additional immune modulation effects due to
      massive virus replication in the brain.

PMID- 18076309
TI  - Norovirus genotypes involved in the outbreaks of gastroenteritis in Croatia
      during the winter season 2004--2005.
AB  - Seven outbreaks and four sporadic cases of the non-bacterial gastroenteritis
      caused by a norovirus (NoV) were detected in Croatia between November 2004 and
      February 2005. An enzyme immunoassay (EIA) and three different RT-PCRs for the
      viral polymerase (ORF1 RT-PCR) and genogroup I (GI) or II (GII) of capsid gene
      regions (GI-ORF2 RT-PCR; GII-ORF2 RT-PCR) were performed to detect NoV in 21
      stool samples. To characterize NoVs, sequencing of the ORF1 region was performed
      on 12 RT-PCR positive samples, whereas the ORF2 region was sequenced for 5 cases.
      Four outbreaks were caused by the genotype GII.4 (Lordsdale) and one outbreak was
      caused by the genotype GI.1 (Norwalk). One of the outbreaks was characterized as
      potentially mixed GII.4 and GI.1 infection. In the monitored period, genotype
      GII.4 dominated as the cause of noroviral infections in adults.

PMID- 18076310
TI  - Inhibition of expression of rna polymerase with small interfering RNAs targeting
      a conserved motif in the respective viral genes in viruses of the family
      Flaviviridae.
AB  - The RNA-dependent RNA polymerase (RdRp) in viruses of the family Flaviviridae
      plays an important role in the viral replication process and in the forming of a
      replicase complex. We used small interfering RNAs (siRNAs) corresponding to the
      highly conservative Motif V of RdRp gene of different viruses to examine their
      role in modulating the expression of RdRp. Evaluation of the expression of RdRps
      was performed by the fluorescence, flow cytometry, Western blotting, and real
      time PCR. We found that Classical swine fever virus (CSFV) siRNA could completely
      block the transcription and expression of RdRp. Additionally, Hepatitis C virus
      (HCV) siRNA could cause effective inhibition of RdRp, whereas Japanese
      encephalitis virus siRNA did not show significant repression of corresponding
      RdRp. These results demonstrated that siRNAs inhibited the expression of tested
      RdRps at the transcription level or at the posttranscriptional processing to a
      different extent.

PMID- 18076311
TI  - Applicability of the stages of change and Weight Efficacy Lifestyle Questionnaire
      with natives of Sarawak, Malaysia.
AB  - INTRODUCTION: There is an increase in the prevalence of overweight and obesity in
      Malaysia. Besides prevalence studies, not much is known about either overweight
      or obese individuals. The objective of this study was to determine the stages of
      change in losing weight and the self-efficacy in eating control of three
      indigenous groups of overweight and obese adults in Sarawak, Malaysia. METHODS: A
      cross-sectional study was conducted in one rural region in Sarawak using a
      purposive sample. A structured questionnaire, which included two scales: (1)
      Weight: Stages of change (SOC) to assess readiness to change; and (2) Weight
      Efficacy Lifestyle Questionnaire (WEL) (both adopted from the transtheoretical
      model of change); and a set of pre-tested questionnaires on socio-demographic
      data, the presence of health problems and self-assessment of weight
      appropriateness, was used to interview respondents. RESULTS: The stage
      distribution for weight loss of these adults respondents (n = 271) showed that
      60.5% (n = 164) were in the pre-contemplation stage, 20.7% (n = 56) were in the
      contemplation stage, 8.5% (n = 23) were in the preparation stage, and 8.9% (n =
      24) were in the action stage, while only 1.5% (n = 4) were in the maintenance
      stage. Except for education, the stage differences were generally stable across
      age, sex, race, household income, presence or absence of health problem, self
      perceived weight and presence of overweight or obesity. Respondents were least
      able to control their eating under social pressure and food availability,
      according to their WEL score. CONCLUSION: A large proportion of the overweight or
      obese adults was not intending to lose weight. The factor structure of the two
      WEL original subscales enabled partial differentiation between respondents who
      were able or unable to resist eating in situations where there were availability
      of food and experienced physical discomfort. The study results indicate the
      importance of assessing individuals' SOC score in order to implement stage
      matched intervention strategies. More studies should be performed in order to
      validate the WEL questionnaire for use with a Malaysian sample.

PMID- 18076312
TI  - Radiotherapy for pediatric brain tumors: when and how.
AB  - Radiotherapy plays a central role in the treatment of pediatric brain tumors.
      Historically, surgical resection alone was the mainstay of treatment for
      pediatric CNS malignancies. During the past 75 years, radiotherapy has been
      incorporated into the upfront treatment of many pediatric brain tumors either as
      adjuvant therapy for resected tumors, definitive treatment for unresectable
      malignancies or as prophylactic therapy for occult microscopic disease. Many CNS
      malignancies, which were once universally fatal are now curable with
      multimodality approaches that integrate surgery, chemotherapy and radiotherapy.
      Unfortunately, the long-term CNS side effects of radiotherapy remain a major
      obstacle for survivors of childhood tumors. In this article we will discuss these
      issues in detail and summarize the ongoing efforts to reduce the risks of these
      toxicities.

PMID- 18076313
TI  - Low-grade gliomas: management issues.
AB  - Low-grade gliomas are relatively rare tumors. The optimal management of these
      tumors remains to be defined and has some controversies associated with it. In
      this review, we present the data that is available to date and some of the issues
      that exist in treating these tumors.

PMID- 18076314
TI  - Glioblastoma multiforme: evidence-based approach to therapy.
AB  - Glioblastoma multiforme (GBM) is the most aggressive of the infiltrating gliomas.
      Standards of care for treatment continue to evolve. In many westernized countries
      standard treatment of GBM at diagnosis includes surgery, radiotherapy and
      chemotherapy. In other parts of the world, chemotherapy that is considered
      beneficial by many is excluded from standard therapy, in large part due to issues
      of cost; treatment may be completely palliative, even limited to corticosteroid
      treatment alone. This review will focus on the current standard of care in the
      USA for newly diagnosed GBM, focusing on the evidence supporting that care.

PMID- 18076315
TI  - Emerging therapies for malignant glioma.
AB  - The current standard of care for malignant gliomas consists of surgery,
      radiotherapy and conventional (DNA-damaging) chemotherapies. These treatments are
      relatively nonspecific and may be applied to all glioma subtypes. Developments in
      cancer medicine, however, now offer the opportunity to direct therapies to
      specific molecular pathways involved in tumorigenesis. This offers the potential
      to tailor treatments to tumor subtypes--perhaps with greater efficacy and less
      toxicity. Many of the so-called targeted therapies are under investigation in the
      treatment of malignant glioma. In this review, we will focus on the use of agents
      that affect signal transduction. In particular, we will review the potential role
      for inhibitors of: tyrosine kinases, targets of rapamycin, farnesyl transferase
      and histone deacetylase. Inhibitors of angiogenesis will also be discussed. Some
      'targeted' therapies are less specific than others, working on more than one
      pathway or receptor, thus complex interactions are possible.

PMID- 18076316
TI  - Epidemiology of brain tumors.
AB  - After lagging behind other brain tumor disciplines in the 1980s, the epidemiology
      of brain tumors is now making progress on several fronts. The Central Brain Tumor
      Registry in the USA has made a complete description of primary brain tumors
      available to researchers. International data suggest that environmental
      components in the etiology of brain tumors are likely to be widely dispersed by
      geography and demographic subgroups. There are few proven causes of brain tumors:
      high-dose ionizing radiation, inherited genetic syndromes and AIDs-related brain
      lymphomas. Promising avenues of research include the role of immune function,
      genetic components in families, metabolic and DNA-repair pathways and
      neurocarcinogen exposures.

PMID- 18076317
TI  - Photon radiotherapy for the treatment of high-grade gliomas.
AB  - High-grade gliomas are diseases characterized by poor overall survival despite
      aggressive multimodality therapy. Radiation therapy has been unequivocally
      established as the mainstay of therapy after surgical intervention, regardless of
      the extent of surgical resection. Despite theoretical and technological advances
      in the planning and delivery of radiation therapy, overall survival remains grim.
      In this review, we outline the evolution of radiation therapy, report the pivotal
      trials that have shaped this therapy and speculate on the future direction of
      this field.

PMID- 18076318
TI  - Targeting epidermal growth factor receptor variant III: a novel strategy for the
      therapy of malignant glioma.
AB  - Immunotherapy represents an exciting approach for the treatment of glioblastoma
      multiforme. The success of this approach depends on the identification of tumor
      specific antigens that can then be exploited to target the tumor. One such
      antigen, the epidermal growth factor receptor variant III (EGFRvIII) is found in
      up to 50% of malignant gliomas. This molecule is an interesting vaccine candidate
      since its expression is tumor specific. Recent preclinical, as well as clinical,
      studies of EGFRvIII-based vaccines suggest a promising role for immunotherapy of
      malignant gliomas. This review focuses on vaccines that target EGFRvIII. We
      review preclinical and clinical data and emphasize the immunological mechanisms
      involved in its therapeutic effect.

PMID- 18076319
TI  - Spectrum of pediatric gliomas: implications for the development of future
      therapies.
AB  - The therapy of gliomas is still challenging. This is especially true for
      pediatric gliomas because response to conventional cytotoxic chemotherapy agents
      and radiation therapy is currently often poor and because therapy-related
      morbidity is a significant problem in children. Stratification of tumors
      according to biologic characteristics and new more targeted therapies therefore
      hold the promise of better tumor control as well as reduced side effects.
      Significant progress has been made in recent years in understanding the biology
      of gliomas. These new insights into the molecular mechanism driving tumor growth
      uncover new potential molecular targets for future therapies. In addition, they
      start to uncover biologically defined tumor subtypes that may have to be
      considered independently in the search for optimal treatment regimens.

PMID- 18076320
TI  - Surgical management of pediatric brain tumors.
AB  - Brain tumors are the most common cause of cancer-related death and the second
      most common form of cancer in pediatric patients. Many of these tumors are
      treated primarily with surgery, either alone or in combination with radiation or
      chemotherapy. Recent advances have lead to greater survival and decreased
      morbidities in childhood brain tumor patients. A full understanding of the
      biology and primary treatment modalities for the particular tumor are essential
      for any professional treating these patients, including the neurosurgeon. Each
      tumor type has features in common with, and unique from, other tumors that need
      to be understood prior to undertaking a rational treatment plan. This article
      summarizes some of these features.

PMID- 18076321
TI  - Emerging role of new transgenic mouse models in glioma research.
AB  - Our understanding of glioma biology has relied heavily on the use of cell lines
      and xenograft animal models. However, the recent development of transgenic mouse
      models offers a unique opportunity to examine the pathophysiology of these tumors
      in immunocompetent models in vivo. Transgenic models are highly informative for a
      number of reasons. First, the resulting tumors are genetically and histologically
      similar to human gliomas. Second, transgenic models allow the study of causality
      of genetic/pathway alterations reminiscent of human gliomas. Third, new therapies
      can be tested in established tumors to truly evaluate their potential efficacy.
      This review describes the available technologies involved in transgenic and
      knockout mouse modeling, including the generation of cell-type-specific genetic
      alterations. Finally, genetics are discussed with a focus on how transgenic
      murine gliomas recapitulate alterations found in human counterparts.

PMID- 18076322
TI  - Convection-enhanced delivery for treatment of brain tumors.
AB  - Recently, innovative therapies have been developed for the treatment of malignant
      gliomas. Unfortunately, adequate delivery of these therapies has been a major
      obstacle to clinical success. Intravenous administration is restricted by the
      presence of the blood-brain barrier while local delivery, such as with drug
      impregnated wafers, results in limited parenchyma penetration. Convection
      enhanced delivery is a promising method for the delivery of macromolecules to the
      CNS. Convection-enhanced delivery involves the infusion of therapeutic agents via
      surgically implanted catheters and uses a pressure gradient to achieve a greater
      volume of distribution compared with that seen with diffusion alone. This article
      will review the development of convection-enhanced delivery and its use in the
      treatment of malignant gliomas.

PMID- 18076323
TI  - Advances in neuro-oncology: novel therapies and clinical trials.

PMID- 18076324
TI  - The Bacillus and Myxococcus developmental networks and their transcriptional
      regulators.
AB  - Studies of endospore formation by Bacillus subtilis and fruiting body development
      of Myxococcus xanthus have revealed key features of regulatory networks that
      govern temporal and spatial gene expression in bacteria. In B. subtilis, sigma
      factor cascades, modulated by other types of transcription factors, regulate
      genes in two cell types that form and communicate with each other during
      starvation-induced sporulation. In M. xanthus, starving cells also send signals
      that alter gene expression, but the cascade to emerge so far involves
      transcription factors other than sigma factors. A hundred thousand cells
      coordinate their movements to build a fruiting body in which spores form. The two
      regulatory networks are compared, and questions that remain are identified.

PMID- 18076325
TI  - Cell turnover and adult tissue homeostasis: from humans to planarians.
AB  - Many fully developed metazoan tissues remain in a state of flux throughout life.
      During physiological cell turnover, older differentiated cells are typically
      eliminated by apoptosis and replaced by the division progeny of adult stem cells.
      Independently, each of these processes has been researched extensively, yet we
      know very little about how cell death and stem cell division are coordinated in
      adult organs. Freshwater planarians are an attractive model organism for research
      in this area. Not only do they undergo a very high rate of somatic cell turnover
      throughout life, but experimental tools are now available to study this process
      in vivo. Together, these attributes provide an opportunity to investigate the
      mechanisms, functions, and regulation of cell turnover in adult tissues.

PMID- 18076326
TI  - Specificity in two-component signal transduction pathways.
AB  - Two-component signal transduction systems enable bacteria to sense, respond, and
      adapt to a wide range of environments, stressors, and growth conditions. In the
      prototypical two-component system, a sensor histidine kinase catalyzes its
      autophosphorylation and then subsequently transfers the phosphoryl group to a
      response regulator, which can then effect changes in cellular physiology, often
      by regulating gene expression. The utility of these signaling systems is
      underscored by their prevalence throughout the bacterial kingdom and by the fact
      that many bacteria contain dozens, or sometimes hundreds, of these signaling
      proteins. The presence of so many highly related signaling proteins in individual
      cells creates both an opportunity and a challenge. Do cells take advantage of the
      similarity between signaling proteins to integrate signals or diversify
      responses, and thereby enhance their ability to process information? Conversely,
      how do cells prevent unwanted cross-talk and maintain the insulation of distinct
      pathways? Here we address both questions by reviewing the cellular and molecular
      mechanisms that dictate the specificity of two-component signaling pathways.

PMID- 18076327
TI  - MHC, TSP, and the origin of species: from immunogenetics to evolutionary
      genetics.
AB  - The acronym Mhc, major histocompatibility complex, is customarily not allied with
      topics in evolutionary biology. Here, however, we attempt to demonstrate that the
      Mhc has much to offer to this discipline and intimate that evolutionary
      biologists who ignore its contributions miss out on a chance of applying a new
      approach to vexing questions. One aspect of the Mhc in particular affords a fresh
      look at the population processes that transform one species into another: the
      trans-species polymorphism, the passage of allelic lineages from ancestral to
      descendant species. We provide examples of using the Mhc polymorphism in
      estimating the size of the founding population of new species, and of analyzing
      the long-term population demographies of phylogenetic lineages. We then extend
      the concept of trans-species polymorphism to other genes, even those not evolving
      under balancing selection, and argue that the phenomenon is widespread between
      closely related species. On the example of the cichlid fishes of Lake Victoria,
      we demonstrate how the concept changes the interpretation of this so-called
      "species flock." We contend that the conclusions reached regarding the cichlid
      fishes apply also to other examples of adaptive radiation, for example that of
      Darwin's finches, and so provide new insights into the nature of speciation in
      general.

PMID- 18076329
TI  - Mammalian meiotic recombination hot spots.
AB  - Our understanding of the details of mammalian meiotic recombination has recently
      advanced significantly. Sperm typing technologies, linkage studies, and
      computational inferences from population genetic data have together provided
      information in unprecedented detail about the location and activity of the sites
      of crossing-over in mice and humans. The results show that the vast majority of
      meiotic recombination events are localized to narrow DNA regions (hot spots) that
      constitute only a small fraction of the genome. The data also suggest that the
      molecular basis of hot spot activity is unlikely to be strictly determined by
      specific DNA sequence motifs in cis. Further molecular studies are needed to
      understand how hot spots originate, function and evolve.

PMID- 18076330
TI  - Systems biology of Caulobacter.
AB  - The dynamic range of a bacterial species' natural environment is reflected in the
      complexity of its systems that control cell cycle progression and its range of
      adaptive responses. We discuss the genetic network and integrated three
      dimensional sensor/response systems that regulate the cell cycle and asymmetric
      cell division in the bacterium Caulobacter crescentus. The cell cycle control
      circuitry is tied closely to chromosome replication and morphogenesis by multiple
      feedback pathways from the modular functions that implement the cell cycle. The
      sophistication of the genetic regulatory circuits and the elegant integration of
      temporally controlled transcription and protein synthesis with spatially dynamic
      phosphosignaling and proteolysis pathways, and epigenetic regulatory mechanisms,
      form a remarkably robust living system.

PMID- 18076328
TI  - DNA transposons and the evolution of eukaryotic genomes.
AB  - Transposable elements are mobile genetic units that exhibit broad diversity in
      their structure and transposition mechanisms. Transposable elements occupy a
      large fraction of many eukaryotic genomes and their movement and accumulation
      represent a major force shaping the genes and genomes of almost all organisms.
      This review focuses on DNA-mediated or class 2 transposons and emphasizes how
      this class of elements is distinguished from other types of mobile elements in
      terms of their structure, amplification dynamics, and genomic effect. We provide
      an up-to-date outlook on the diversity and taxonomic distribution of all major
      types of DNA transposons in eukaryotes, including Helitrons and Mavericks. We
      discuss some of the evolutionary forces that influence their maintenance and
      diversification in various genomic environments. Finally, we highlight how the
      distinctive biological features of DNA transposons have contributed to shape
      genome architecture and led to the emergence of genetic innovations in different
      eukaryotic lineages.

PMID- 18076331
TI  - Mendelian genetics of apomixis in plants.
AB  - Apomixis, asexual reproduction through seeds, has the potential to revolutionize
      agriculture if its genetic basis can be elucidated. However, the genetic control
      of natural apomixis has remained obscure until quite recently, owing to all the
      complications of Mendelian genetics, such as epistatic gene interactions,
      components that are expressed sporophytically and gametophytically, expression
      modifiers, polyploidy, aneuploidy, segregation distortion, suppressed
      recombination, etc., that seem to have accumulated during the evolution of
      apomixis. In this review we show how molecular markers and superior phenotypic
      methods have been used to clarify the genetics of apomixis in monocots as well as
      dicots during the past 15 years. Many of the complexities in the genetics of
      apomixis are likely secondary and have evolved as a consequence of the
      reproductive process. New mapping techniques, such as comparative mapping,
      linkage disequilibrium mapping, and deletion mapping, and new high-throughput
      sequencing methods, will help to penetrate the core of apomixis chromosomal
      regions. If the evolutionary genetic load can be exposed and removed, the
      apomixis genes may be used in agriculture as a tool to fix elite genotypes.

PMID- 18076332
TI  - Use of y chromosome and mitochondrial DNA population structure in tracing human
      migrations.
AB  - Well-resolved molecular gene trees illustrate the concept of descent with
      modification and exhibit the opposing processes of drift and migration, both of
      which influence population structure. Phylogenies of the maternally inherited
      mtDNA genome and the paternally inherited portion of the nonrecombining Y
      chromosome retain sequential records of the accumulation of genetic diversity.
      Although knowledge regarding the diversity of the entire human genome will be
      needed to completely characterize human genetic evolution, these uniparentally
      inherited loci are unique indicators of gender in modulating the extant
      population structure. We compare and contrast these loci for patterns of
      continuity and discreteness and discuss how their phylogenetic diversity and
      progression provide means to disentangle ancient colonization events by
      pioneering migrants from subsequent overlying migrations. We introduce new
      results concerning Y chromosome founder haplogroups C, DE, and F that resolve
      their previous trifurcation and improve the harmony with the mtDNA recapitulation
      of the out-of-Africa migration.

PMID- 18076333
TI  - A surveillance study of escitalopram treatment of depressed patients.
AB  - AIM: The aim of this surveillance study was to assess the tolerability of, and
      response to, treatment with escitalopram in 525 psychiatric out-patient clinics
      in the Czech Republic. METHODS: Clinical response was evaluated using the Zung
      Depression Rating Scale (ZDRS) and the Clinical Impressions--Improvement (CGI-I)
      scale. The change from baseline in the ZDRS, Clinical Impressions--Severity of
      Illness (CGI-S) and CGI-I scores were analysed for each visit (baseline, weeks 1
      2, 4, 8 and 26). RESULTS: There were 2664 patients included, with 2126 patients
      (79.8%) completing the 6-month treatment. During the course of the study, the
      patients showed an improvement in their severity of depression, with a response
      rate (CGI-I < or = 2) of 86.7% and a remission rate (CGI-S < or = 2) of 80.6% for
      patients completing 6 months of treatment. The most frequent adverse events were
      nausea (5.5%), headache (2.1%) and sweating (2.0%). Discontinuation due to
      adverse events occurred in 170 patients (6.4%) and 3.7% of patients withdrew from
      the study because of non-response and/or worsening of psychopathology. There were
      no significant differences between baseline and final visit in mean body mass
      index for men or women. CONCLUSION: In this large surveillance study,
      escitalopram was well tolerated by a heterogeneous group of patients, whose
      depressive symptoms responded to < or = 6 months of treatment.

PMID- 18076334
TI  - Impact of amiodarone on the ability of anterior fat pad retention to prevent
      postcoronary arterial bypass grafting atrial fibrillation incidence: a substudy
      of the AFIST III (Atrial Fibrillation Suppression Trial III).
AB  - BACKGROUND: In the AFIST III (Atrial Fibrillation Suppressions Trial III),
      anterior fat pad (AFP) retention did not decrease the incidence of postoperative
      atrial fibrillation (POAF), but prophylaxis with amiodarone did. In order to
      examine the inter-relationship between amiodarone with AFP retention on POAF, we
      performed a planned subgroup analysis of AFIST III. METHODS: Coronary artery
      bypass graft (CABG) patients were randomized to AFP maintenance or removal with
      prophylactic amiodarone used via the discretion of the caregiver. Patients were
      categorized into four groups: AFP retention alone, AFP retention plus amiodarone,
      AFP removal alone and AFP removal plus amiodarone. Multivariate logistic
      regression was used to calculate adjusted odds ratios with 95% confidence
      intervals for development of POAF. RESULTS: Amiodarone was used in 28% of the 178
      patients (mean age = 66 +/- 10, 80% male, 5% previous atrial fibrillation)
      undergoing CABG surgery. The overall POAF occurrence rate, regardless of subgroup
      designation was 35.4%. On multivariate logistic regression, amiodarone plus AFP
      retention was associated with an 81% reduction in the odds of the patient
      developing POAF (p = 0.015). Amiodarone prophylaxis without AFP retention was
      associated with a 68% reduction (p = 0.040). CONCLUSION: Amiodarone prophylaxis
      with or without AFP retention is an independent negative predictor of POAF.
      Combining amiodarone with AFP retention may provide a synergistic effect in the
      prevention of POAF. Further studies are needed to validate the results of this
      study.

PMID- 18076335
TI  - An update on therapeutics for tobacco dependence.
AB  - The aim of this review is to consider the clinical trial evidence for the
      efficacy of four classes of pharmacological treatment for nicotine dependence:
      nicotine replacement, antidepressants, nicotine-receptor partial agonists and
      drugs blocking cannabinoid receptors. Despite falls in many developed countries,
      the prevalence of smoking remains high and is increasing in developing countries.
      Stopping smoking before middle age substantially reduces the mortality associated
      with tobacco use. Although many people quit without formal help, both non
      pharmacological and pharmacological interventions can help people to stop
      smoking. Drug therapies target neural pathways to reduce withdrawal symptoms
      associated with psychopharmacological dependence on nicotine. Nicotine
      replacement therapy and some antidepressants aid smoking cessation and are an
      established part of therapy. Newer pharmacological approaches include the use of
      the selective nicotinic partial agonists, varenicline and cytisine, and compounds
      targeting cannabinoid receptors (rimonabant). Recent evidence suggests that the
      nicotine-receptor partial agonist varenicline is at least as effective as
      nicotine replacement therapy and antidepressants.

PMID- 18076336
TI  - Carbapenems: a potent class of antibiotics.
AB  - The purpose of this review is to assess the relative strengths and weaknesses of
      individual members of the carbapenem class of antibiotics. Clinical trials and
      review articles were identified from a Medline search (1979 - July 2006), in
      addition to, reference citations from identified publications, abstracts from the
      Interscience Conferences on Antimicrobial Agents and Chemotherapy and the 12th
      International Congress on Infectious Disease, and package inserts. Articles in
      English were reviewed, with emphasis on those containing efficacy or safety data.
      Carbapenems bind to critical penicillin-binding proteins, disrupting the growth
      and structural integrity of bacterial cell walls. They provide enhanced anaerobic
      and Gram-negative coverage as compared with other beta-lactams and their
      stability against extended-spectrum beta-lactamases (ESBLs) makes them an
      effective treatment option. The most common adverse effects are infusion-site
      complications and gastrointestinal distress. Ertapenem has limited efficacy
      against non-fermenting, Gram-negative bacteria, restricting its use to community
      acquired infections. Imipenem is slightly more effective against Gram-positive
      organisms and meropenem slightly more effective against Gram-negative organisms.
      However, both have broad-spectrum activity, including non-fermenting, Gram
      negative bacteria. Among non-fermenting, Gram-negatives, resistance to imipenem
      in particular is increasing. Doripenem is in late-stage clinical development and
      combines the broad-spectrum coverage of imipenem and meropenem, and more potent
      activity against Pseudomonas aeruginosa. Due to the increasing challenges
      represented by ESBLs and multi-drug resistant organisms, the carbapenems are
      assuming a greater role in the treatment of serious infections. Imipenem and
      meropenem are presently available and have been shown to be effective against
      nosocomial infections. Doripenem is an investigational carbapenem that has
      completed Phase III clinical trials and that has the potential to improve on this
      efficacy and minimize the emergence of resistance to the carbapenem class.

PMID- 18076337
TI  - Treatment options for lipodystrophy in HIV-positive patients.
AB  - The HIV-associated lipodystrophy syndrome is one of the major side effects of HIV
      therapy. Its metabolic abnormalities may harbor a significant risk for
      cardiovascular disease with as yet unknown consequences. Present data indicate a
      rather multifactorial pathogenesis where HIV infection, its therapy and patient
      related factors are major contributors. Therapeutic interventions in patients
      with lipodystrophy have so far been of only limited success in many cases.
      General recommendations include dietary changes and lifestyle modifications,
      altering antiretroviral drug therapy (substitution of stavudine and zidovdine
      with e.g., abacavir or tenofovir or replacement of protease inhibitors with non
      nucleoside reverse-transcriptase inhibitors), and finally, the use of
      metabolically active drugs. Here, the treatment options of the HIV-lipodystrophy
      syndrome are summarized based on the present literature.

PMID- 18076338
TI  - Conservative treatment for Peyronie's disease: an update.
AB  - Many theories have been proposed to explain the cause of Peyronie's disease (PD);
      however, the true pathogenesis of PD remains an enigma. As a result, the
      treatment of PD remains a dilemma and new therapies continue to evolve. The last
      two decades have witnessed a phenomenal advance in the understanding of the
      pathophysiology and natural history of PD. The efficacy of conservative treatment
      for PD is not settled. In this update review the authors provide information of
      the status of conservative therapy for PD. Conservative treatment is always the
      initial treatment in most of the cases. This kind of therapy consists of
      different modalities of treatment such as oral, intralesional or topical therapy.
      Other treatments including iontophoresis, extracorporeal shock wave,
      radiotherapy, ultrasound and laser have also been reported.

PMID- 18076339
TI  - Medical therapy for pulmonary arterial hypertension.
AB  - Recent advances in the understanding of pulmonary arterial hypertension have led
      to new therapeutic options, although the disease remains incurable and continues
      to cause substantial morbidity and mortality. Disease-specific therapies have
      been approved for use in the US, including epoprostenol and its various analogs,
      endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. The use of
      combination therapy with agents from more than one of these drug classes is
      becoming increasingly common, although guidelines establishing optimal
      combinations are lacking. Meanwhile, potential future therapeutic options are
      actively being pursued.

PMID- 18076340
TI  - Clinical management of chronic obstructive pulmonary disease and asthma in an
      obese patient.
AB  - The prevalence of obesity has noticeably increased worldwide. The clinician is
      now frequently facing the challenge of managing patients with concomitant chronic
      obstructive pulmonary disease (COPD) or asthma and obesity. Obesity is often
      associated with a poorer control of these chronic respiratory diseases and the
      optimal management of these conditions in the presence of obesity remains to be
      determined. Herein, the authors review the present understanding of the influence
      of obesity in the development, clinical manifestations and management of asthma
      and COPD. The influence of weight loss, response to present therapies as well as
      new targets for the treatment of COPD and asthma in obese subjects are also
      discussed, in addition to future directions for research.

PMID- 18076341
TI  - Economic evaluation of the use of enoxaparin in non-ST-elevation acute coronary
      syndrome.
AB  - This paper reviews the published literature on the costs and benefits of low
      molecular-weight heparins (LMWHs) compared with unfractionated heparin (UFH), in
      patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS).
      Although LMWH has superior efficacy to UFH in NSTE-ACS, it must also provide cost
      effectiveness or net-cost savings before its wide use can be approved by
      healthcare payers. The drug-acquisition costs of LMWH are higher than those of
      UFH, but economic analyses should also consider the initial medical resource
      consumption and the downstream costs associated with failed treatment and
      subsequent care. Based on published economic analyses, the incremental drug costs
      of LMWH compared with UFH are compensated for by savings in medical-resource
      costs secondary to reducing ischemic events in NSTE-ACS patients.

PMID- 18076342
TI  - Diagnosis and treatment of vitamin D deficiency.
AB  - The recent discovery--in a randomised, controlled trial--that daily ingestion of
      1100 IU of colecalciferol (vitamin D) over a 4-year period dramatically reduced
      the incidence of non-skin cancers makes it difficult to overstate the potential
      medical, social and economic implications of treating vitamin D deficiency. Not
      only are such deficiencies common, probably the rule, vitamin D deficiency stands
      implicated in a host of diseases other than cancer. The metabolic product of
      vitamin D is a potent, pleiotropic, repair and maintenance, secosteroid hormone
      that targets > 200 human genes in a wide variety of tissues, meaning it has as
      many mechanisms of action as genes it targets. A common misconception is that
      government agencies designed present intake recommendations to prevent or treat
      vitamin D deficiency. They did not. Instead, they are guidelines to prevent
      particular metabolic bone diseases. Official recommendations were never designed
      and are not effective in preventing or treating vitamin D deficiency and in no
      way limit the freedom of the physician--or responsibility--to do so. At this
      time, assessing serum 25-hydroxy-vitamin D is the only way to make the diagnosis
      and to assure that treatment is adequate and safe. The authors believe that
      treatment should be sufficient to maintain levels found in humans living
      naturally in a sun-rich environment, that is, > 40 ng/ml, year around. Three
      treatment modalities exist: sunlight, artificial ultraviolet B radiation or
      supplementation. All treatment modalities have their potential risks and
      benefits. Benefits of all treatment modalities outweigh potential risks and
      greatly outweigh the risk of no treatment. As a prolonged 'vitamin D winter',
      centred on the winter solstice, occurs at many temperate latitudes, < or = 5000
      IU (125 microg) of vitamin D/day may be required in obese, aged and/or dark
      skinned patients to maintain adequate levels during the winter, a dose that makes
      many physicians uncomfortable.

PMID- 18076343
TI  - High hopes at high altitudes: pharmacotherapy for acute mountain sickness and
      high-altitude cerebral and pulmonary oedema.
AB  - The pharmacotherapy of prevention and treatment of acute altitude- related
      problems - acute mountain sickness, high-altitude cerebral oedema and high
      altitude pulmonary oedema - is reviewed. Drug therapy is only part of the answer
      to the medical problems of high altitude; prevention should include slow ascent
      and treatment of the more severe illnesses should include appropriate descent.
      Carbonic anhydrase inhibitors, in particular acetazolamide, remain the most
      effective drugs in preventing, to a large extent, the symptoms of acute mountain
      sickness, and can be used in the immediate management of the more severe forms of
      altitude-related illnesses. Glucocorticoids in relatively large doses are also
      effective preventative drugs, but at present are largely reserved for the
      treatment of the more severe acute mountain sickness and acute cerebral oedema.
      Calcium channel blockers and PDE-5 inhibitors are effective in the management of
      acute pulmonary oedema. Further work is required to establish the role of
      antioxidants and anticytokines in these syndromes.

PMID- 18076344
TI  - Olmesartan medoxomil plus hydrochlorothiazide for treating hypertension.
AB  - Although achieving blood pressure (BP) control is critical to improve
      cardiovascular prognosis in hypertensive patients, many of them fail to attain
      the targets. Most patients with hypertension need more than one antihypertensive
      agent to achieve the goals. Combination therapy is required when monotherapy
      fails to attain BP objectives (< 140/90 mmHg in general hypertensive population;
      < 130/80 mmHg in high-risk groups) and as a first-line treatment in certain
      situations, such as markedly elevated BP values, high or very high cardiovascular
      risk patients or when lower targets are warranted. The advantages of combination
      therapy are well documented with the potential for increased antihypertensive
      efficacy as a result of different mechanisms of action, and a lower incidence of
      adverse effects because of the lower doses used and the possible compensatory
      responses. The inhibition of the renin-angiotensin system appears to be very
      beneficial in the treatment of patients with hypertension. Olmesartan medoxomil
      20 mg/hydrochlorothiazide 12.5 mg is the latest combination of an angiotensin
      receptor blocker and a diuretic approved for treatment of hypertension. The aim
      of this manuscript is to update the published data about the efficacy and safety
      of this fixed combination.

PMID- 18076345
TI  - Efficacy and safety of bimatoprost/timolol fixed combination in the treatment of
      glaucoma or ocular hypertension.
AB  - When a single medication does not adequately control intraocular pressure,
      additional intraocular hypotensive agents are often added to the therapeutic
      regime. However, regimen complexity has been associated with reduced patient
      compliance. Treatment with a fixed combination may, therefore, increase
      compliance as a result of simplifying the dosage regimen. Bimatoprost/timolol
      fixed combination (BTFC) combines two clinically effective agents that decrease
      elevated intraocular pressure by independent mechanisms. In two clinical studies,
      BTFC was more effective than its individual components. Furthermore, in a non
      inferiority study BTFC has been shown to be as effective as the association of
      its individual components. BTFC was clinically effective and generally well
      tolerated, with no unexpected adverse reactions reported for the BTFC compared
      with those reported for bimatoprost or timolol monotherapies.

PMID- 18076346
TI  - Is sapropterin treatment suitable for all subjects with phenylketonuria?
AB  - In a Phase I study, 20% of subjects with phenylketonuria (96/485) responded with
      a > or = 30% reduction in blood phenylalanine at day 8 of treatment with
      sapropterin. Subsequently, some of the responders from this study were enrolled
      in a Phase III study. The subjects with phenylketonuria were randomised to
      sapropterin 10 mg/kg/day (n = 41) or placebo (n = 47) for 6 weeks and continued
      their usual diet. The primary end point was the mean change from baseline in
      phenylalanine level after 6 weeks and there was a reduction of 235 micromol/l in
      the sapropterin group compared with 2.9 micromol/l in the placebo group. Thus, in
      the 20% of subjects with phenylketonuria that responded to a trial treatment with
      sapropterin, there were reduced mean blood phenylalanine levels over 6 weeks of
      treatment. In summary, sapropterin effectively reduces blood phenylalanine levels
      in a small proportion of subjects with phenylketonuria.

PMID- 18076347
TI  - Changes in serum fetuin-A and inflammatory markers levels in end-stage renal
      disease (ESRD): effect of a single session haemodialysis.
AB  - BACKGROUND: The aim of the present study was to evaluate the effect of a single
      haemodialysis (HD) session on serum fetuin-A levels, considered a negative acute
      phase response marker; moreover, we evaluated the behaviour of fibrinogen and
      high sensitivity C-reactive protein (hsCRP) as acute phase response and
      chronic/subclinical inflammation markers, respectively, after a single HD
      session. METHODS: Serum fetuin-A, albumin, hsCRP and fibrinogen were measured in
      72 patients before and after a single HD session. RESULTS: After a single HD
      session, we observed a significant increase in fibrinogen levels, while fetuin-A
      levels decreased (p<0.05). Also, hsCRP levels were significantly increased.
      CONCLUSIONS: The significant decrease of fetuin-A levels after a single HD
      session is consistent with the hypothesis of HD-induced inflammation; activated
      acute phase response and fetuin-A deficiency might account for increased
      cardiovascular risk and accelerated atherogenesis in dialysis patients.

PMID- 18076348
TI  - Evaluation of a novel standardized system for collection and quantification of
      oral fluid.
AB  - BACKGROUND: Standardization in collection and testing of oral fluid is lacking.
      METHODS: A novel standardized collection and quantification system for oral fluid
      testing was evaluated. Sample collection volumes were determined. For
      determination of the saliva content in oral fluid samples, tartrazine, which is
      an integral part of the saliva extraction solution serving as an internal
      standard, was used. Results were compared with those obtained by employing
      glucose as a 'supplemental internal standard' for determination. Analytical
      performance of the new system for collection and quantification of oral fluid was
      evaluated. Calcium and magnesium analyte concentrations in oral fluid samples
      were measured with a routine laboratory method and compared to a reference
      method. RESULTS: Volumes of oral fluid samples collected ranged from 4.9 to 10.5
      mL. The mean saliva content in oral fluid samples was found to be 65.5 percent by
      volume (vol.-%) when determined through the tartrazine concentration and 65.0
      vol.-% when determined through the glucose concentration. Evaluation of
      analytical performance revealed interassay imprecision coefficients of variation
      (CVs) ranging from 1.5% to 3.2% and intraassay imprecision CVs from 1.1% to 2.5%.
      When linearity was tested, a quasi-linear curve was observed (R2=0.99).
      Comparison of two different methods for determination of calcium and magnesium
      concentrations showed correlations of R2=0.96 for calcium and R2=0.97 for
      magnesium. CONCLUSIONS: The new system for collection and quantification of oral
      fluid helps to improve standardization of pre-analytics in oral fluid testing and
      to provide reliable and accurate quantification of analytes in oral fluid
      samples.

PMID- 18076349
TI  - Age-related changes of plasma glycosaminoglycans.
AB  - BACKGROUND: This study was undertaken to reveal how the physiological ageing
      process influences plasma glycosaminoglycans (GAGs) content and composition.
      METHODS: GAGs isolated from plasma samples obtained from 105 healthy subjects
      were quantified using a hexuronic acid assay and subjected to electrophoretic
      fractionation. RESULTS: We found that total GAGs decreased gradually with
      advancing age. The electrophoretic analysis allowed identifying chondroitin
      sulfates, dermatan sulfates and heparan sulfates and heparin in plasma of healthy
      individuals. Chondroitin sulfates, predominant plasma GAGs, showed declining
      values with age and displayed higher structural diversity in subjects from the
      first five decades of life compared to older subjects. An age-related increase in
      plasma dermatan sulfates content during the first four decades of life followed
      by a decrease in a later period of life was apparent. Structural heterogeneity of
      these glycans was found in subjects until 10 years of age. Heparan sulfates and
      heparin plasma levels were inversely correlated with age until 25 years of age,
      without age-dependent changes thereafter. These macromolecules displayed higher
      heterogeneity of structure in subjects over 50 years of age than in younger
      subjects. CONCLUSIONS: The obtained results indicate that age should be taken
      into account in all studies investigating blood GAGs alterations during
      pathological conditions.

PMID- 18076350
TI  - A family with multiple mutations and sequence variations in the alpha- and beta
      globin gene clusters.
AB  - BACKGROUND: Usually, laboratory diagnostics of hereditary hemoglobin disorders is
      fairly straightforward. Sometimes, however, correct diagnosis can be difficult.
      In this study, we describe a family with multiple mutations and sequence
      variations in the alpha- and beta-globin gene clusters. METHODS: Hemocytometry
      results were obtained using an automated cell counter. Hemoglobin variant
      analysis was performed by cation-exchange HPLC. PCR and DNA sequence analyses
      were used to identify mutations in the globin genes. RESULTS: The proposita was
      referred to our laboratory for hematological evaluation [hemoglobin 145 g/L (119
      155 g/L) mean corpuscular volume 72 fl (80-97 fl), mean corpuscular hemoglobin 26
      pg (28-36 pg), erythrocytes 5.6 x 10(12)/L (3.7-5.0 10(12)/L)]. Characterization
      and quantification of hemoglobin variants showed 11.3% HbA1, 4.4% HbA2, 58.9% HbC
      and 23.0% HbF. Subsequent analysis revealed, in addition to a heterozygous HbC
      mutation, the presence of a beta-thalassemia causing mutation (-90C>T), a
      heterozygous alpha-thalassemia (-alpha(-3.7)/alpha alpha) and three different
      gamma-globin sequence variations. Additional molecular analysis was performed in
      all family members. CONCLUSIONS: In the family presented in this study, 10
      different mutations were found in the globin genes. Molecular analysis was
      necessary to clarify hemoglobin variant analysis, in particular the low amount of
      HbA1 in the proposita. Knowledge of the molecular background facilitates in the
      understanding of the hematological parameters and proper counseling of the
      patient.

PMID- 18076351
TI  - Evaluation of the GEM Premier 4000: a compact blood gas CO-Oximeter and
      electrolyte analyzer for point-of-care and laboratory testing.
AB  - BACKGROUND: GEM Premier 4000 (Instrumentation Laboratory), a new blood gas/CO
      Oximeter/hematocrit/electrolyte/glucose/lactate analyzer was evaluated. The only
      reagents required were disposable cartridges (GEM Premier 4000 PAK comprise all
      components necessary for analysis, including quality controls). METHODS: The
      evaluation was performed in two laboratories according to the Valtec protocol
      guidelines. Analytical performances (imprecision at three levels, linearity,
      inaccuracy by method comparison using patient samples, interferences) and
      instrument practicability were compared with three routinely used laboratory
      blood gas analyzers (ABL 835 and 725, Radiometer; OMNI S, Roche Diagnostics) and
      the centrifuged microhematocrit method. RESULTS: Within-run and between-run
      imprecision yielded good coefficients of variation values for all parameters.
      Linearity was satisfactory and within the expected ranges provided by the
      manufacturer. Method comparisons demonstrated close agreement (Deming's
      regression correlation coefficients 0.92-1.00). No interferences of lipemia,
      hyperbilirubinemia and hemolysis were found on CO-Oximetry parameters. Fetal
      hemoglobin >35% overestimated carboxyhemoglobin measurements, but the magnitude
      of error was reduced with the fetal hemoglobin correction analysis mode.
      CONCLUSION: The GEM Premier 4000 analytical performance was validated for all
      parameters with the accuracy and the reliability of traditional systems. This
      blood gas analyzer fulfills most of the requirements for both point-of-care and
      laboratory use.

PMID- 18076352
TI  - Evaluation of a new Sebia isoelectrofocusing kit for alpha 1-antitrypsin
      phenotyping with the Hydrasys System.
AB  - BACKGROUND: Laboratory evaluation of alpha 1-antitrypsin (A1AT) deficiency is
      generally performed by determination of A1AT concentrations and identification of
      specific allelic variants by phenotyping. For this purpose, we evaluated a new
      Hydragel 18 A1AT Isofocusing kit on the semi-automatic Hydrasys System (Sebia)
      for the determination of A1AT phenotypes by isoelectrofocusing on ready-to-use
      agarose gels with specific immunological detection. METHODS: Serum samples from
      66 patients were analysed with this new kit in comparison with the conventional
      and manually performed isoelectrofocusing method on polyacrylamide gels with
      Coomassie Blue staining. RESULTS: A1AT phenotypes showed comparable iso
      electrofocusing patterns in both systems. The good within-gel reproducibility of
      this kit was demonstrated using two normal serum samples (M1 and M1M2 phenotypes)
      and six pathological serum samples with different phenotypes (MS, SS, SZ, MZ,
      ZZ). A sensitivity study was undertaken by performing serial dilutions on a serum
      with a ZZ phenotype containing 0.27 g/L A1AT. The detection limit was 0.050 g/L.
      CONCLUSIONS: This new method is highly specific, rapid and simple to perform. It
      improves identification of not only the most common but also various rare A1AT
      phenotypes. It appears to be suitable for routine analysis and screening
      applications in a clinical laboratory setting.

PMID- 18076353
TI  - Probing the redox activity of T-lymphocytes deposited at electrode surfaces with
      voltammetric methods.
AB  - BACKGROUND: Reactive oxygen species and redox signaling play an important role in
      the regulation of many vital biological processes. However, they are also tightly
      connected with many pathological conditions. The detection and evaluation of
      these signaling events are very often accompanied with great difficulties. In
      this article, we describe the development of a novel electrochemically-based
      technique for monitoring the cellular redox state. METHODS AND RESULTS: T-cells
      were attached on the surface of a working electrode, which was modified with 2
      palmitoylhydroquinone as a redox mediator. Using cyclic voltammetry, we were able
      to indirectly (via the redox mediator) monitor an electron transport from the
      cells towards the working electrode, which enabled us to evaluate the redox
      activity of the cells. CONCLUSIONS: This new technique is rather simple and
      sensitive and may be used in the future as a valid diagnostic procedure in
      various branches of biomedical science.

PMID- 18076354
TI  - 'Likelihood-ratio' and 'odds' applied to monitoring of patients as a supplement
      to 'reference change value' (RCV).
AB  - BACKGROUND: Interpretation of serial data in monitoring of patients is usually
      performed by use of the 'reference change value' (RCV). While this tool for
      interpretation of measured differences is simple and clear, there are a number of
      drawbacks attached to the uncritical use of this concept. It is a dichotomised
      interpretation of continuous data using a fixed probability without any counter
      hypothesis. Therefore, a tool for better understanding and interpretation of
      measured differences in monitoring is needed. THEORY: The concept of sensitivity,
      specificity, likelihood ratios and odds used for diagnostic test evaluations is
      applied to monitoring by substituting measured concentrations with measured
      differences. Thus, two frequency distributions of differences are assumed, one
      for a stable, steady-state, situation and one for a certain change. Values
      exceeding a measured difference will thus represent 'false change' for the stable
      and 'true change' for the change and the ratio between these will define the
      likelihood. By making the hypothesis of change variable and equal to the actual
      difference, the distribution corresponding to the true changes for the measured
      difference varies with this. Consequently, the likelihood ratio for change
      increases with growing measured difference and when used together with the pre
      test odds or pre-test probability, the post-test odds and post-test probability,
      related to the clinical situation, can be calculated. RESULTS: One example is
      acute intermittent porphyria, where increasing excretion of porphobilinogen is
      characteristic for an attack. The within-subject biological variation is
      estimated to 25%, which for two measurements gives a variation of 35% for
      measured differences. Three pre-test probabilities are assumed and illustrate
      that post-test odds and probability depends on both the pre-test probability and
      the measured difference. A second example is monitoring women in a follow-up
      after treatment of breast cancer, using the tumour marker CA 15-3. The within
      subject biological variation is estimated to 14.9% and for differences 21%
      (2(1/2) x 14.9 due to two measurements). Here, the monitoring is totally
      scheduled and the frequency of progression depends on the time after treatment.
      Thus, the pre-test probability varies with time so that a certain measured
      difference with a given likelihood ratio will result in varying post-test odds
      depending on time. CONCLUSIONS: The concept presented here expands the earlier
      concept of RCVs by making it possible to have an estimate of the post-test odds
      for a certain difference to occur based on likelihood ratios and pre-test odds.

PMID- 18076355
TI  - A rapid and sensitive method to detect specific human lymphocyte antigen (HLA)
      class II alleles associated with celiac disease.
AB  - BACKGROUND: Celiac disease (CD) is a complex disorder triggered by gluten
      affecting genetically predisposed individuals. More than 90% of patients carry
      human lymphocyte antigen (HLA)-DQ2 (DQA1*05, DQB1*02) and/or HLA-DQ8 (DQA1*03,
      DQB1*0302). We propose the use of the DQ-CD Typing kit that allows identification
      of the HLA class II alleles (DQA1*0201,*03,*05, DQB1*02,*0302, DRB1*03,*04,*07)
      selected to be informative in the CD risk evaluation and of a second kit, namely
      DQ-CD Zygosis, for DQB1*02 homozygosity determination. METHODS: The study was
      performed on a cohort of 100 individuals previously HLA typed with commercial
      kits. Fresh blood or previously extracted DNA was amplified in a unique PCR
      program using allele-specific primers and visualized on agarose gel. RESULTS: DNA
      amplification yielded strong and clear products without non specific signals or
      ghost bands. All the samples showed the expected alleles in accordance with the
      previous HLA typing. CONCLUSIONS: The DQ-CD Typing and Zygosis kits are fast,
      simple, economical and accurate tools that can be used to determinate the HLA
      DQ2/DQ8 status in laboratory practice addressed for the diagnosis of CD.
      Molecular HLA testing is considered a valid support in the confirmation/exclusion
      of CD, especially in high-risk groups, such as CD relatives, or when serological
      and histological data are ambiguous.

PMID- 18076356
TI  - Assay-dependent variability of serum insulin levels during oral glucose tolerance
      test: influence on reference intervals for insulin and on cut-off values for
      insulin sensitivity indices.
AB  - BACKGROUND: The oral glucose tolerance test (oGTT) is the most common method to
      estimate indices of insulin sensitivity in clinical as well as in epidemiological
      studies. The aim of this study was to investigate the variability of insulin
      levels for reference intervals and of insulin sensitivity indices during oGTT by
      three different insulin immunoassays. METHODS: Serum insulin levels were
      determined during oGTT of randomly selected adult subjects (total n=101, with
      n=68 with normal glucose tolerance) by the LIAISON (LIA), the Elecsys (EL) and
      the AutoDELFIA (AD) method. RESULTS: Sensitivity and precision of all three
      insulin assays were comparable. Insulin levels demonstrated a close (p<0.001)
      interassay correlation (LIA vs. EL: r=0.987, LIA vs. AD: r=0.966, EL vs. AD:
      r=0.965). Insulin levels and insulin sensitivity indices (n=68) of the AD method
      were significantly different compared to the LIA or EL assay (p<0.001). Basal
      insulin levels demonstrated an assay-dependent significant body mass index (BMI)
      dependency (LIA: r=0.24, p=0.05; AD: r=0.44, p<0.001; EL: r=0.36, p<0.01) in the
      regression analysis. At 120 min post glucose, gender was the relevant influencing
      factor on insulin levels of the LIA (r=0.40, p<0.001), AD (r=0.37, p<0.01) and EL
      (r=0.40 p<0.001) method. CONCLUSIONS: We conclude that assay-dependent reference
      intervals should be used for the clinical interpretation of insulin levels from
      oGTT and of insulin sensitivity indices. Moreover, BMI and gender have to be
      considered as influencing factors.

PMID- 18076357
TI  - Comparison of creatinine-based estimations of glomerular filtration rate in
      endurance athletes at rest.
AB  - BACKGROUND: Several creatinine-based estimates of the glomerular filtration rate
      (GFR) have been advocated as reliable alternatives to the urinary clearance of
      exogenous filtration markers. The Cockcroft-Gault (C-G) equation requires a body
      weight parameter, which was not included in the Modification of Diet in Renal
      Disease (MDRD) Study and the Mayo Clinic Quadratic Equation (MCQE) formulas.
      However, there is little information on the lifestyle influences on these
      equations, especially the intensity and the type of physical activity. METHODS:
      We evaluated the differences in the GFR, as estimated by the MDRD, MCQE and C-G
      equations, in 60 professional male cyclists at rest and 60 healthy sedentary
      matched controls. RESULTS: Professional cyclists had significantly lower body
      weight, body mass index and serum creatinine concentration than healthy sedentary
      individuals. We also observed a significantly higher MDRD-estimated GFR in
      athletes than in controls (119 mL/min/1.73 m2 vs. 104 mL/min/1.73 m2, p<0.001),
      whereas the GFR values estimated by both the MCQE (137 vs. 135, p=0.128) and C-G
      (127 vs. 127, p=0.490) formulas did not differ significantly. As compared to the
      MDRD values, the mean GFR calculated by the MCQE and C-G formulas was
      overestimated by 29% and 23% in the sedentary population, and by 17% and 7% in
      athletes, respectively. A lower bias was observed when comparing C-G with MCQE
      estimated values in both the sedentary [mean: -5%, 95% confidence interval (CI): 
      32% to 22%] and athlete (mean: -6%, 95% CI: -41% to 29%) populations. The
      correlation among the different equations in healthy sedentary individuals was
      always significant, whereas the only significant association in the athletes was
      that between MCQE and C-G values. CONCLUSIONS: The results of this study attest
      that the three most widely used creatinine-based formulas produce significant
      variations in the estimated GFR in a population of endurance athletes at rest.
      Probably, the use of C-G or MCQE formulas might be more suitable in this context,
      as they globally appear more robust against variations of the training regimen.

PMID- 18076358
TI  - Modeling the variability of creatinine measurements improves estimates of the
      glomerular filtration rate.
AB  - BACKGROUND: The precision of the formulae used to estimate glomerular filtration
      rate (GFR) decreases when the serum creatinine (SCr) assay is biased compared
      with the assay used during the development of the formulae. METHODS: For 100
      children referred for 51Cr-EDTA clearance (CLEDTA), SCr was measured with a JAFFE
      (classic Jaffe colorimetric creatinine assay), a compensated Jaffe (COMP), an
      enzymatic (ENZ) and an HPLC assay. A population pharmacokinetics approach based
      on a non-linear mixed effects model (NONMEM) was used to model the relationships
      between the CLEDTA and physiopathological/analytical variables. RESULTS: Unlike
      JAFFE values, COMP and ENZ SCr gave a high bias using the Schwartz formula for
      the GFR calculation (median +27.0% and +39.1%, respectively). The best equation
      obtained from the analysis of the curves of [51Cr-EDTA]plasma vs. time was
      (n=67): CLEDTA (mL/min)=61.9 x [SCr (microM)/Theta]Psi x [age (years)/13.4]0.522
      x (weight (kg)/44.2)0.233. The SCr assay-related coefficients and exponents were
      Theta=97.4, Psi=-0.757 (-0.922; -0.592) for JAFFE; Theta=85.3, Psi=-0.579 (
      0.681; -0.477) for COMP; and Theta=82.6, Psi=-0.560 (-0.659; -0.460) for ENZ.
      When applied to 33 children, this equation estimated CL(EDTA) without any
      significant bias: +3.1% (-11.8; +11.4) for COMP and +5.3% (-7.2; +16.4) for ENZ.
      CONCLUSIONS: As long as there is no standardization of SCr measurements,
      population pharmacokinetics may be a powerful tool to model inter-assay
      variability.

PMID- 18076359
TI  - Tumor necrosis factor-alpha G(-308)A promoter polymorphism, matrix
      metalloproteinase (MMP)-3 5A/6A gene variation, MMP-9 C(-1562)T promoter
      polymorphism and risk and extent of ischemic heart disease.

PMID- 18076360
TI  - Long-term prognostic value of mid-regional pro-adrenomedullin and C-terminal pro
      endothelin-1 in patients with acute myocardial infarction.
AB  - BACKGROUND: Mid-regional pro-adrenomedullin (MR-proADM) and endothelin-1 have
      been shown to predict mortality of patients with acute myocardial infarction.
      However, the prognostic value of both biomarkers in predicting long-term clinical
      events after acute myocardial infarction remains unclear. METHODS: In a
      prospective study, 30 patients suffering from acute ST elevation myocardial
      infarction or non-ST elevation myocardial infarction were enrolled. Measurements
      of MR-proADM and CT-pro-endothelin-1 (CT-proET-1) were performed at initial
      presentation, 2 or 3 days and 4 months after acute myocardial infarction. Long
      term clinical events (e.g., recurrent myocardial infarction, percutaneous
      transluminal coronary angioplasty, aorto-coronary venous bypass or cardiogenic
      shock) were documented over a period from the 4th until the 10th month. RESULTS:
      Both MR-proADM and CT-proET-1 were able to differentiate patients with subsequent
      long-term clinical events (n=11) from those without (n=19). At the time of acute
      myocardial infarction, median MR-proADM level of the event group was 0.69 nmol/L
      as compared to 0.59 nmol/L of the no-event group (p=0.036). A difference was
      still observed after 3 days (event group median 0.66 nmol/L; no-event group
      median 0.57 nmol/L; p=0.022). Accordingly, median CT-proET-1 level was 72.9
      pmol/L in the event group as compared to a median of 54.4 pmol/L in patients in
      the no-event group (p=0.009) 3 days after acute myocardial infarction. Within the
      acute phase, patients with MR-proADM levels > or =0.67 nmol/L were 3 times more
      likely (relative risk 2.8; 95% confidence interval 1.2-6.9; p=0.042) to suffer
      from a future clinical event. The area under the curve (AUC) was 0.71 (95%
      confidence interval 0.51-0.86; p=0.046). After 3 days, patients with CT-proET-1
      levels > or =57 pmol/L were 6 times more likely (relative risk 5.9; 95%
      confidence interval 0.9-40.4; p=0.036) to suffer from a future clinical event.
      The AUC was 0.76 (95% confidence interval 0.55-0.90; p=0.015). CONCLUSIONS:
      Elevated levels of MR-proADM and CT-proET-1 during the acute phase of myocardial
      infarction may predict an adverse long-term clinical outcome.

PMID- 18076361
TI  - N-terminal proB-type natriuretic peptide (NT-proBNP) concentrations in elite
      rugby players at rest and after active and passive recovery following strenuous
      training sessions.
AB  - BACKGROUND: The serum biomarker N-terminal proB-type natriuretic peptide (NT
      proBNP), a cleaved fragment of the brain natriuretic peptide (BNP) precursor
      (amino acids 1-76), is accepted as a standard marker for evaluating and
      monitoring cardiac injury characterized by myocardial wall stress. Strenuous
      exercise may generate transitory ischemia, myocardial stress and diastolic left
      ventricular dysfunction, possibly inducing increased concentrations of NT-proBNP.
      A purported caveat to prolonged strenuous exercise is based on evidence for
      biochemical and structural signs of heart dysfunction in recreational athletes
      after continuous exertion. METHODS: We compared NT-proBNP levels in three groups
      of physically fit subjects: top-level rugby players, professional soccer players
      and healthy controls. NT-proBNP concentrations were measured at rest and after an
      intensive training session followed by two different recovery strategies (passive
      or active). RESULTS: A comparison of the three samples showed that NT-proBNP
      concentrations in the rugby players were lower than those in controls at rest and
      were similar to those in professional soccer players. Elevated post-training NT
      proBNP levels were unaffected by the type of recovery. The relatively high NT
      proBNP levels after active recovery when psychophysical stress is higher, because
      of cycling and cold water immersion, suggest that not only endurance exercise,
      but also strenuous, stressful short exercise can induce an increase in NT-proBNP
      concentrations. CONCLUSIONS: In this sample of professional athletes, NT-proBNP
      was low at rest, and the increase after physical exercise was physiological.

PMID- 18076362
TI  - Polyethylene glycol interference in the Immulite prolactin assay: treatment of
      the calibrators with polyethylene glycol does not improve diagnostic accuracy.

PMID- 18076363
TI  - CTLA-4 polymorphism 49A-G is associated with placental abruption and preeclampsia
      in Finnish women.
AB  - BACKGROUND: Our aim was to study genetic variability in the gene encoding
      cytotoxic T-lymphocyte antigen (CTLA-4) and individual susceptibility to the
      development of preeclampsia or placental abruption. METHODS: A total of 361 women
      (132 with preeclampsia, 117 with placental abruption and 112 healthy controls)
      were genotyped for 49A-G polymorphism (dbSNP: rs231775) in the CTLA-4 gene.
      RESULTS: The frequency of the G alleles was significantly higher in women with
      preeclampsia than in controls (51.1% vs. 42.0%; OR 1.44, 95% CI 1.01-3.48,
      p<0.043). Women with placental abruption had decreased frequency of AA genotype
      (22.2% vs. 35.7%) and significantly more AG or GG genotypes compared with
      controls (OR 1.94, 95% CI 1.09-2.07, p<0.024). No significant differences were
      detected in the frequencies of genotype GG (29.5%, 21.4% and 19.6%, respectively)
      between the three groups. CONCLUSIONS: Our data suggest that the 49A-G
      polymorphism in the CTLA-4 gene is associated with the development of placental
      abruption and preeclampsia, with women having the G allele being at risk.

PMID- 18076365
TI  - Relationship between thiolactonase activity and hyperhomocysteinemia according to
      MTHFR gene polymorphism in Tunisian Behcet's disease patients.
AB  - BACKGROUND: Behcet's disease (BD) is a multisystemic immuno-inflammatory
      disorder. Inflammatory processes may cause lipid peroxidation, alteration of
      lipid profile and increase the risk of atherosclerosis. The aim of this study was
      to evaluate the association between thiolactonase (HTLase) activity and plasma
      homocysteine levels (tHcy) in a BD population and to investigate their
      association with methylenetetrahydrofolate reductase (MTHFR) 677C-->T genotype.
      METHOD: A total of 35 BD patients were compared to 39 healthy volunteers.
      RESULTS: Significantly higher tHcy levels associated with lower HTLase activities
      were found in BD patients as compared to healthy controls (p<0.001). These
      patients also exhibited lower values of triglycerides and high-density
      lipoprotein cholesterol (HDL-C). Homozygosity for the T allele of the MTHFR gene
      was more frequent in BD patients (14.3% vs. 7.7%). It was associated with
      significantly higher tHcy levels (16.9 micromol/L for n=17 vs. 13.1 micromol/L
      for n=18; p<0.05) and markedly lower HTLase activity (362.6+/-156.7 U/L vs.
      414.2+/-180.2 U/L) for the (TT+CT) and CC genotypes, respectively. Moreover, HDL
      C levels were inversely correlated with tHcy (r=-0.5; p=0.004) but positively
      associated with HTLase activity (r=0.374; p=0.038). These correlations were also
      present in several clinical manifestations, such as ocular, neurological
      involvement or thrombosis. CONCLUSIONS: Homozygosity of the T allele of the MTHFR
      gene is prevalent in BD patients. High levels of tHcy associated with low HTLase
      activities may be one of the causes leading to thrombosis in BD patients.

PMID- 18076366
TI  - Metalloproteases as potential therapeutic targets in arthritis treatment.
AB  - Dysregulated proteolysis of the extracellular matrix of articular cartilage
      represents a unifying hallmark of the arthritides, and has been a target for
      therapeutic intervention for some time, although clinical efficacy has been
      elusive. Members of the 'A disintegrin and metalloprotease with thrombospondin
      motifs' and matrix metalloprotease families are considered to be collectively
      responsible for cartilage catabolism, such that inhibition of these activities is
      theoretically a highly attractive strategy for preventing further proteolytic
      damage. This review outlines the biology of these metalloproteases and what we
      have learnt from inhibition studies and transgenics, and highlights the important
      questions that this information raises for the future development of therapeutics
      directed towards metalloproteases for arthritis treatment.

PMID- 18076367
TI  - Targeting ischemic brain injury with intravenous immunoglobulin.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) is a therapeutic modality approved
      for the treatment of autoimmune disorders. OBJECTIVE: This review discusses how
      IVIG can prevent brain damage following ischemic stroke and discuss the potential
      mechanisms of action. METHODS: Medline and the world wide web were searched and
      the relevant literature was classified under the following categories: IVIG, IVIG
      mechanism of action, and ischemic stroke injury mechanisms. RESULTS/CONCLUSION:
      Brain ischemia induces an inflammatory response that contributes to neuronal cell
      death. Because of its ability to block multiple molecular events, IVIG may have
      particularly strong neuroprotective action against ischemic brain injury. In
      light of the extensive clinical experience with IVIG for other indications,
      development of clinical trials to evaluate the use of IVIG in human stroke
      patients are warranted.

PMID- 18076368
TI  - Superior cervical ganglion-10 protein as a molecular effector of c-Jun N-terminal
      kinase 1: implications for the therapeutic targeting of Jun N-terminal kinase in
      nerve regeneration.
AB  - BACKGROUND: Cell stress and tissue injury lead to c-Jun N-terminal kinase (JNK)
      activation, which is known to contribute to cell death. Paradoxically, strong
      evidence supports an important role for JNK in the regeneration of neuronal
      processes, subsequent to injury. OBJECTIVE: Recent research revealed the growth
      cone-associated protein superior cervical ganglion-10 protein as a candidate
      effector for the regeneration pathway mediated by JNK1. This implies that
      neuroprotective strategies targeting JNK may have negative effects on neuronal
      regeneration, unless JNK1 function is spared, and that the mechanistic
      relationships between JNK1 and neuronal regeneration deserve increased attention.
      RESULTS: This review proposes a model reconciling the microtubule regulatory
      properties of superior cervical ganglion protein 10 with its role as a JNK
      effector of regeneration and highlight remaining issues to be resolved.

PMID- 18076369
TI  - An update on the development of drugs for neuropsychiatric disorders: focusing on
      the sigma 1 receptor ligand.
AB  - The sigma1 receptor is an intracellular molecule that shares no homology with any
      mammalian proteins. sigma1 receptors normally localize at the endoplasmic
      reticulum and regulate a variety of signal transductions including intracellular
      Ca2+ dynamics and neurotrophic factor signaling. In the brain, sigma1 receptors
      are known to regulate the activity of diverse ion channels via protein-protein
      interactions. Accumulated evidences strongly indicate that the
      activation/upregulation of sigma1 receptors promotes the neuronal differentiation
      as well as a robust antiapoptotic action. In animals, sigma1 receptor agonists
      exhibit an antidepressant-like action. Furthermore, the agonists enhanced
      neuronal survival eventhough they were administered several hours after a brain
      ischemia. Thus, primary clinical targets of sigma1 receptor ligands are proposed
      to include stroke, neurodegenerative disorders and depression. Ligands for the
      sigma1 receptor may constitute a new class of therapeutic drugs targeting an
      endoplasmic reticular protein.

PMID- 18076370
TI  - Targeting synuclein-gamma to counteract drug resistance in cancer.
AB  - BACKGROUND: Expression of synuclein-gamma (SNCG) protein is elevated in the
      advanced stages of many types of cancers, including ovarian, lung, liver,
      esophagus, colon, prostate and, in particular, breast. In breast carcinoma, SNCG
      is causatively linked to stimulated proliferation, metastasis and drug
      resistance. OBJECTIVE: To establish SNCG as a potential therapeutic target and to
      discuss clinical use of SNCG inhibiting peptide. METHODS: This review focuses on
      the plausible mechanisms of SNCG activity, SNCG mediated drug resistance and its
      inhibition. RESULTS/CONCLUSION: Evidence based research shows that the aberrant
      expression of SNCG has a strong correlation with breast cancer progression and
      poor clinical outcome. A peptide based inhibitor counters activity of SNCG, which
      may be developed as an adjuvant therapy.

PMID- 18076371
TI  - Aurora kinase inhibitors: identification and preclinical validation of their
      biomarkers.
AB  - Aurora kinases are key regulators of mitosis and inhibitors being developed by a
      wide range of pharmaceutical and biotechnology companies for the treatment of
      cancer. Tumor cells respond differentially on inhibition of different Aurora
      kinase family members and these differences have to be considered in the clinical
      development of small-molecule inhibitors with respect to the chosen indications,
      the schedules or the selection of appropriate end points and they should also
      guide the development of biomarkers. Preclinical validation of potential
      biomarkers for Aurora kinase inhibitors led to a first application in clinical
      trials, as exemplified for the phosphorylation of histone H3 to follow Aurora-B
      inhibition. This review discusses the criteria for translation into the clinic
      and the value of pharmacodynamic biomarkers and their potential, but also their
      limitations to be used as surrogate markers for clinical end points.

PMID- 18076372
TI  - Topiramate and type 2 diabetes: an old wine in a new bottle.
AB  - Topiramate, a marketed antiepileptic drug, has been used to treat seizures and
      allied neurological problems since 1999. Recently, a series of newer findings for
      the use of topiramate have cropped up, which include Type 2 diabetes and obesity.
      In a series of clinical studies, a subset of neurological patients with Type 2
      diabetes mellitus (T2DM) serendipitously showed better glycaemic control when
      treated with topiramate. It has since been demonstrated that topiramate can act
      both as an insulin secretagogue and sensitiser in T2DM animal models.
      Pathogenesis of Type 2 diabetes involves both beta-cell dysfunction and insulin
      resistance. Therefore, an agent that has dual action (insulin secretagougue and
      sensitisation) is preferred for T2DM. Topiramate seems to act through multiple
      mechanisms to ameliorate diabetic symptoms, some of them unknown. Hence, it
      becomes imperative to discuss its probable modes of action. Topiramate raises new
      hope as an antidiabetic agent or a potential new chemotype with a better safety
      profile for the treatment of T2DM.

PMID- 18076373
TI  - AMP activated protein kinase: a next generation target for total metabolic
      control.
AB  - Metabolic syndrome is characterized by a cluster of metabolic disorders, such as
      reduced glucose tolerance, hyperinsulinemia, hypertension, visceral obesity and
      lipid disorders. The benefit of exercise in maintaining total metabolic control
      is well known and recent research indicates that AMP-activated protein kinase
      (AMPK) may play an important role in exercise-related effects. AMPK is considered
      as a master switch in regulating glucose and lipid metabolism. AMPK is an enzyme
      that works as a fuel gauge, being activated in conditions of high phosphate
      depletion. In the liver, activation of AMPK results in decreased production of
      plasma glucose, cholesterol, triglyceride and enhanced fatty acid oxidation. AMPK
      is also robustly activated by skeletal muscle contraction and myocardial
      ischemia, and is involved in the stimulation of glucose transport and fatty acid
      oxidation by these stimuli. In adipose tissue, activated AMPK inhibits deposition
      of fat, but enhances breakdown and burning of stored fat, resulting in reduction
      of body weight. The two leading diabetic drugs, namely metformin and
      rosiglitazone, and adipokines, such as adiponectin and leptin, show their
      metabolic effects partially through AMPK. These data suggest that AMPK may be a
      key player in the development of new treatments for obesity, Type 2 diabetes and
      the metabolic syndrome. In this review, the author provide insight into the role
      of AMPK as a probable target for treatment of metabolic syndrome.

PMID- 18076374
TI  - Privileged scaffolds targeting reverse-turn and helix recognition.
AB  - BACKGROUND: Protein-protein interactions dominate molecular recognition in
      biologic systems. One major challenge for drug discovery arises from the very
      large surfaces that are characteristic of many protein-protein interactions.
      OBJECTIVES: To identify 'drug-like' small molecule leads capable of modulating
      protein-protein interactions based on common protein-recognition motifs, such as
      alpha-helices, beta-strands, reverse-turns and polyproline motifs for example.
      OVERVIEW: Many proteins/peptides are unstructured under physiologic conditions
      and only fold into ordered structures on binding to their cellular targets.
      Therefore, preorganization of an inhibitor into its protein-bound conformation
      reduces the entropy of binding and enhances the relative affinity of the
      inhibitor. Accordingly, this review describes a general strategy to address the
      challenge based on the 'privileged structure hypothesis' [Che, PhD thesis,
      Washington University, 2003] that chemical templates capable of mimicking
      surfaces of protein-recognition motifs are potential privileged scaffolds as
      small-molecule inhibitors of protein-protein interactions. The authors highlight
      recent advances in the design of privileged scaffolds targeting reverse-turn and
      helical recognition. CONCLUSIONS: Privileged scaffolds targeting common protein
      recognition motifs are useful to help elucidate the receptor-bound conformation
      and to provide non-peptidic, bioavailable substructures suitable for optimization
      to modulate protein-protein interactions.

PMID- 18076375
TI  - Applying small RNA molecules to the directed treatment of human diseases:
      realizing the potential.
AB  - Small interfering RNAs (siRNA) and microRNAs (miRNA) are gaining considerable
      attention in the pharmaceutical and biotechnology industries, as research has
      revealed their likely clinical and agricultural applications. The capacity of
      siRNAs to dramatically and specifically reduce the expression of targeted genes
      has spawned multiple clinical trials to establish the therapeutic potential of
      small RNAs targeting viral, cancer and other disease-related genes. The
      successful application of siRNAs will enable the development of therapeutic
      applications based on miRNAs that have been observed to contribute to a variety
      of human diseases. This article reviews advances that have been made to apply
      small RNAs as therapeutics.

PMID- 18076376
TI  - Genetic disruption of calpain correlates with loss of membrane blebbing and
      differential expression of RhoGDI-1, cofilin and tropomyosin.
AB  - Dynamic regulation of the actin cytoskeleton is important for cell motility,
      spreading and the formation of membrane surface extensions such as lamellipodia,
      ruffles and blebs. The ubiquitous calpains contribute to integrin-mediated
      cytoskeletal remodelling during cell migration and spreading, by cleavage of
      focal adhesion components and signalling molecules. In the present study, the
      live-cell morphology of calpain-knockout and wild-type cells was examined by time
      lapse fluorescence microscopy, and a role of calpain in mediating the formation
      of sporadic membrane blebs was established. Membrane blebbing was significantly
      reduced in calpain-knockout cells, and genetic rescue fully restored the wild
      type phenotype in knockout cells. Proteomic comparison of wild-type and knockout
      cells identified decreased levels of RhoGDI-1 (Rho GDP-dissociation inhibitor)
      and cofilin 1, and increased levels of tropomyosin in calpain-knockout cells,
      suggesting a role of calpain in regulating membrane extensions involving these
      proteins. RhoGDI, cofilin and tropomyosin are known regulators of actin filament
      dynamics and membrane extensions. The reduced levels of RhoGDI-1 in calpain
      knockout cells observed by proteome analysis were confirmed by immunoblotting.
      Genetic rescue of the calpain-knockout cells enhanced RhoGDI-1-expression 2-fold
      above that normally present in wild-type cells. These results suggest a
      regulatory connection between calpain and RhoGDI-1 in promoting formation of
      membrane blebs.

PMID- 18076377
TI  - A dominant-negative ESCRT-III protein perturbs cytokinesis and trafficking to
      lysosomes.
AB  - In eukaryotic cells, the completion of cytokinesis is dependent on membrane
      trafficking events to deliver membrane to the site of abscission. Golgi and
      recycling endosomal-derived proteins are required for the terminal stages of
      cytokinesis. Recently, protein subunits of the ESCRT (endosomal sorting complexes
      required for transport) that are normally involved in late endosome to lysosome
      trafficking have also been implicated in abscission. Here, we report that a
      subunit, CHMP3 (charged multivesicular body protein-3), of ESCRT-III localizes at
      the midbody. Deletion of the C-terminal autoinhibitory domain of CHMP3 inhibits
      cytokinesis. At the midbody, CHMP3 does not co-localize with Rab11, suggesting
      that it is not present on recycling endosomes. These results combined provide
      compelling evidence that proteins involved in late endosomal function are
      necessary for the end stages of cytokinesis.

PMID- 18076378
TI  - Metalloprotease-mediated OPA1 processing is modulated by the mitochondrial
      membrane potential.
AB  - BACKGROUND INFORMATION: Human OPA1 (optic atrophy type 1) is a dynamin-related
      protein of the mitochondrial IMS (intermembrane space) involved in membrane
      fusion and remodelling. Similarly to its yeast orthologue Mgm1p that exists in
      two isoforms generated by the serine protease Pcp1p/Rbd1p, OPA1 exists in various
      isoforms generated by alternative splicing and processing. In the present paper,
      we focus on protease processing of OPA1. RESULTS: We find that various mammalian
      cell types display a similar pattern of OPA1 isoforms [two L-OPA1 (long isoforms
      of OPA1) and three S-OPA1 (short isoforms of OPA1)] and that loss of the inner
      membrane potential, but not inhibition of oxidative phosphorylation or
      glycolysis, induces rapid and complete processing of L-OPA1 to S-OPA1. In
      isolated mitochondria, OPA1 processing was inhibited by heavy-metal chelators,
      pointing to processing by a mitochondrial metalloprotease. The pattern of OPA1
      isoforms and its processing kinetics were normal in mitochondria devoid of the
      serine protease PARL (presenilins-associated rhomboid-like protein) - the human
      orthologue of Pcp1/Rbd1 - and in cells from patients carrying homozygous
      mutations in SPG7 (spastic paraplegia type 7), a gene encoding the matrix
      oriented metalloprotease paraplegin. In contrast, OPA1 processing kinetics were
      delayed upon knock-down of YME1L (human yme1-like protein), an IMS-oriented
      metalloprotease. OPA1 processing was also stimulated during apoptosis, but
      inhibition of this processing did not affect apoptotic release of OPA1 and
      cytochrome c. Finally, we show that all OPA1 isoforms interact with Mfn1
      (mitofusin 1) and Mfn2 and that these interactions are not affected by
      dissipation of DeltaPsim (inner mitochondrial membrane potential) or OPA1
      processing. CONCLUSIONS: Metalloprotease-mediated processing of OPA1 is modulated
      by the inner membrane potential and is likely to be mediated by the YME1L
      protease.

PMID- 18076379
TI  - Mutations in a small region of the exportin Crm1p disrupt the daughter cell
      specific nuclear localization of the transcription factor Ace2p in Saccharomyces
      cerevisiae.
AB  - BACKGROUND INFORMATION: The CBK1 gene of Saccharomyces cerevisiae encodes a
      protein kinase that is a member of the NDR (nuclear Dbf2-related) family of
      protein kinases, which are involved in morphogenesis and cell proliferation.
      Previous studies have shown that deletion of CBK1 leads to a loss of polarity and
      the formation of large aggregates of cells. This aggregation phenotype is due to
      the loss of the daughter cell-specific accumulation of the transcription factor
      Ace2p, which is responsible for the transcription of genes whose products are
      necessary for the final separation of the mother and the daughter at the end of
      cell division. RESULTS: We show that the daughter cell-specific localization of
      Ace2p does not occur via a specific localization of the ACE2 mRNA and that, in
      vivo, the transcription of CTS1, one of the principal targets of Ace2p, is
      daughter cell-specific. We have shown that extragenic suppressors of the
      Deltacbk1 aggregation phenotype are located in the nuclear exportin CRM1 and
      ACE2. These mutations disrupt the interaction of Ace2p and Crm1p, thus impairing
      Ace2p export and resulting in the accumulation of the protein in both mother and
      daughter cell nuclei. CONCLUSIONS: We propose that in the daughter cell nucleus
      Cbk1p phosphorylates the Ace2p nuclear export signal, and that this
      phosphorylation blocks the export of Ace2p via Crm1p, thus promoting the daughter
      cell-specific nuclear accumulation of Ace2p.

PMID- 18076380
TI  - Lamellipodin proline rich peptides associated with native plasma
      butyrylcholinesterase tetramers.
AB  - BChE (butyrylcholinesterase) protects the cholinergic nervous system from
      organophosphorus nerve agents by scavenging these toxins. Recombinant human BChE
      produced from transgenic goat to treat nerve agent intoxication is currently
      under development. The therapeutic potential of BChE relies on its ability to
      stay in the circulation for a prolonged period, which in turn depends on
      maintaining tetrameric quaternary configuration. Native human plasma BChE
      consists of 98% tetramers and has a half-life (t((1/2))) of 11-14 days. BChE in
      the neuromuscular junctions and the central nervous system is anchored to
      membranes through interactions with ColQ (AChE-associated collagen tail protein)
      and PRiMA (proline-rich membrane anchor) proteins containing proline-rich
      domains. BChE prepared in cell culture is primarily monomeric, unless expressed
      in the presence of proline-rich peptides. We hypothesized that a poly-proline
      peptide is an intrinsic component of soluble plasma BChE tetramers, just as it is
      for membrane-bound BChE. We found that a series of proline-rich peptides was
      released from denatured human and horse plasma BChE. Eight peptides, with masses
      from 2072 to 2878 Da, were purified by HPLC and sequenced by electrospray
      ionization tandem MS and Edman degradation. All peptides derived from the same
      proline-rich core sequence PSPPLPPPPPPPPPPPPPPPPPPPPLP (mass 2663 Da) but varied
      in length at their N- and C-termini. The source of these peptides was identified
      through database searching as RAPH1 [Ras-associated and PH domains (pleckstrin
      homology domains)-containing protein 1; lamellipodin, gi:82581557]. A proline
      rich peptide of 17 amino acids derived from lamellipodin drove the assembly of
      human BChE secreted from CHO (Chinese-hamster ovary) cells into tetramers. We
      propose that the proline-rich peptides organize the 4 subunits of BChE into a 340
      kDa tetramer, by interacting with the C-terminal BChE tetramerization domain.

PMID- 18076381
TI  - Selective binding of phorbol esters and diacylglycerol by individual C1 domains
      of the PKD family.
AB  - The PKD (protein kinase D) family are novel DAG (diacylglycerol) receptors. The
      twin C1 domains of PKD, designated C1a and C1b, have been shown to bind DAG or
      phorbol esters. However, their ligand-binding activities and selectivities have
      not been fully characterized. Here, binding activities of isolated C1a, C1b and
      intact C1a-C1b domains to DAG and phorbol esters were analysed. The isolated C1b
      domains of PKD isoforms bind [(3)H]PDBu ([20-(3)H]phorbol 12, 13-dibutyrate) with
      similar high affinities, while they exhibit weaker affinities towards a synthetic
      DAG analogue, DOG (1,2-dioctanoyl-sn-glycerol), as compared to the control.
      Mutating a conserved lysine residue at position 22 to tryptophan in C1b of PKD3
      fully restores its affinity to DOG, indicating that this residue accounts for its
      weaker affinity to DOG. In contrast, the non-consensus residues in the isolated
      C1a domain of PKD mainly contribute to maintaining the protein's structural fold,
      since converting these residues in C1a of PKD3 to those in PKD1 or PKD2
      drastically reduces the maximal number of active receptors, while only minimally
      impacting ligand-binding activities. Moreover, ligand-binding activities of C1a
      and C1b are sensitive to the structural context in an intact C1a-C1b domain and
      exhibit unique patterns of ligand selectivity. C1a and C1b in the intact C1a-C1b
      of PKD1 are opposite in selectivity for PDBu and DOG. In contrast, C1a of PKD3
      exhibits 48-fold higher affinity to DOG as compared to C1b, although both domains
      bind PDBu with equivalent affinities. Accordingly, mutating C1a of a full-length
      PKD3-GFP greatly reduces DOG-induced plasma membrane translocation, but does not
      affect that induced by PMA. In summary, individual C1 domains of PKD isoforms
      differ in ligand-binding activity and selectivity, implying isoform-selective
      regulation of PKD by phorbol esters and DAG.

PMID- 18076383
TI  - Rab10 in insulin-stimulated GLUT4 translocation.
AB  - In fat and muscle cells, insulin stimulates the movement to and fusion of
      intracellular vesicles containing GLUT4 with the plasma membrane, a process
      referred to as GLUT4 translocation. Previous studies have indicated that Akt
      [also known as PKB (protein kinase B)] phosphorylation of AS160, a GAP (GTPase
      activating protein) for Rabs, is required for GLUT4 translocation. The results
      suggest that this phosphorylation suppresses the GAP activity and leads to the
      elevation of the GTP form of one or more Rabs required for GLUT4 translocation.
      Based on their presence in GLUT4 vesicles and activity as AS160 GAP substrates,
      Rabs 8A, 8B, 10 and 14 are candidate Rabs. Here, we provide further evidence that
      Rab10 participates in GLUT4 translocation in 3T3-L1 adipocytes. Among Rabs 8A,
      8B, 10 and 14, only the knockdown of Rab10 inhibited GLUT4 translocation. In
      addition, we describe the subcellular distribution of Rab10 and estimate the
      fraction of Rab10 in the active GTP form in vivo. Approx. 5% of the total Rab10
      was present in GLUT4 vesicles isolated from the low-density microsomes. In both
      the basal and the insulin state, 90% of the total Rab10 was in the inactive GDP
      state. Thus, if insulin increases the GTP form of Rab10, the increase is limited
      to a small portion of the total Rab10. Finally, we report that the Rab10 mutant
      considered to be constitutively active (Rab10 Q68L) is a substrate for the AS160
      GAP domain and, hence, cannot be used to deduce rigorously the function of Rab10
      in its GTP form.

PMID- 18076382
TI  - Elevated intracellular calcium increases ferritin H expression through an NFAT
      independent post-transcriptional mechanism involving mRNA stabilization.
AB  - An increase in intracellular Ca2+ is one of the initiating events in T-cell
      activation. A calcium-mediated signalling cascade in T-cells involves activation
      of calcineurin and the dephosphorylation and translocation of NFAT (nuclear
      factor of activated T-cells), resulting in the transcriptional activation of
      target genes such as IL-2 (interleukin-2). In the present study, we found that
      increased intracellular calcium leads to induction of the antioxidant protein
      ferritin H. We previously reported that the ferritin H gene is transcriptionally
      activated under oxidative stress conditions through an ARE (antioxidant
      responsive element). The facts that the ferritin H ARE contains a composite AP-1
      (activator protein 1) site and that NFAT collaborates with AP-1 transcription
      factors led us to test whether calcium-activated NFAT is involved in the ferritin
      H induction through the ARE. Treatment of Jurkat T-cells with the calcium
      ionophore, ionomycin, increased ferritin H mRNA and protein expression. Although
      NFAT translocated to the nucleus and bound a consensus NFAT sequence located in
      the IL-2 promoter after ionomycin treatment, it did not activate ferritin H
      transcription despite the presence of a putative NFAT-binding sequence in the
      ferritin H ARE. In addition, the calcineurin inhibitor cyclosporin A treatment
      blocked ionomycin-mediated NFAT nuclear translocation but failed to abrogate the
      increase in ferritin H mRNA. Analysis of mRNA stability after actinomycin D
      treatment revealed that ionomycin prolongs ferritin H mRNA half-life. Taken
      together, these results suggest that ionomycin-mediated induction of ferritin H
      may occur in an NFAT-independent manner but through post-transcriptional
      stabilization of the ferritin H mRNA.

PMID- 18076384
TI  - Oxidative folding competes with mitochondrial import of the small Tim proteins.
AB  - All small Tim proteins of the mitochondrial intermembrane space contain two
      conserved CX(3)C motifs, which form two intramolecular disulfide bonds essential
      for function, but only the cysteine-reduced, but not oxidized, proteins can be
      imported into mitochondria. We have shown that Tim10 can be oxidized by
      glutathione under cytosolic concentrations. However, it was unknown whether
      oxidative folding of other small Tims can occur under similar conditions and
      whether oxidative folding competes kinetically with mitochondrial import. In the
      present study, the effect of glutathione on the cysteine-redox state of Tim9 was
      investigated, and the standard redox potential of Tim9 was determined to be
      approx. -0.31 V at pH 7.4 and 25 degrees C with both the wild-type and Tim9F43W
      mutant proteins, using reverse-phase HPLC and fluorescence approaches. The
      results show that reduced Tim9 can be oxidized by glutathione under cytosolic
      concentrations. Next, we studied the rate of mitochondrial import and oxidative
      folding of Tim9 under identical conditions. The rate of import was approx. 3-fold
      slower than that of oxidative folding of Tim9, resulting in approx. 20% of the
      precursor protein being imported into an excess amount of mitochondria. A similar
      correlation between import and oxidative folding was obtained for Tim10.
      Therefore we conclude that oxidative folding and mitochondrial import are
      kinetically competitive processes. The efficiency of mitochondrial import of the
      small Tim proteins is controlled, at least partially in vitro, by the rate of
      oxidative folding, suggesting that a cofactor is required to stabilize the
      cysteine residues of the precursors from oxidation in vivo.

PMID- 18076385
TI  - Intergenerational class mobility in contemporary Britain: political concerns and
      empirical findings.
AB  - In Britain in recent years social mobility has become a topic of central
      political concern, primarily as a result of the effort made by New Labour to make
      equality of opportunity rather than equality of condition a focus of policy.
      Questions of the level, pattern and trend of mobility thus bear directly on the
      relevance of New Labour's policy analysis, and in turn are likely be crucial to
      the evaluation of its performance in government. However, politically motivated
      discussion of social mobility often reveals an inadequate grasp of both empirical
      and analytical issues. We provide new evidence relevant to the assessment of
      social mobility - in particular, intergenerational class mobility - in
      contemporary Britain through cross-cohort analyses based on the NCDS and BCS
      datasets which we can relate to earlier cross-sectional analyses based on the
      GHS. We find that, contrary to what seems now widely supposed, there is no
      evidence that absolute mobility rates are falling; but, for men, the balance of
      upward and downward movement is becoming less favourable. This is overwhelmingly
      the result of class structural change. Relative mobility rates, for both men and
      women, remain essentially constant, although there are possible indications of a
      declining propensity for long-range mobility. We conclude that under present day
      structural conditions there can be no return to the generally rising rates of
      upward mobility that characterized the middle decades of the twentieth century -
      unless this is achieved through changing relative rates in the direction of
      greater equality or, that is, of greater fluidity. But this would then produce
      rising rates of downward mobility to exactly the same extent - an outcome
      apparently unappreciated by, and unlikely to be congenial to, politicians
      preoccupied with winning the electoral 'middle ground'.

PMID- 18076386
TI  - Social stratification and attitudes: a comparative analysis of the effects of
      class and education in Europe.
AB  - A classic topic in the sociology of inequality lies in the subjective
      consequences of people's stratification position. Many studies have shown that
      education and occupational class have significant effects on attitudes, but
      little is known about how the magnitude of these effects depends on the societal
      context. There has been debate in the scholarly literature, with some authors
      arguing that effects of class and education are less important when societies are
      more developed, whereas other authors argue that effects are either stable (for
      class) or increasing (for education). We use a meta-analytical design to address
      this debate. More specifically we examine the effects of class and education for
      a broad range of attitudes (21 scales) in 22 European countries using data from
      the 1999 wave of the European Values Study. We pool summary-measures of
      association (Eta-values) into a new dataset and analyse these Eta-values (N =
      453) applying multilevel models with characteristics of countries and
      characteristics of attitudes as the independent variables. Our results show that
      there is no evidence that the effects of class on attitudes are lower when
      countries are more modern, but we do find larger effects of education in more
      modern countries.

PMID- 18076387
TI  - Are clerical workers proletarian? A case study of the Australian Public Service.
AB  - This paper explores whether clerical workers have been proletarianized by using
      the Australian Public Service (APS) as a case study. It shows that before the
      late 1980s the market, work and status situations of APS clerks were
      predominantly proletarian since they were typified by limited career prospects,
      low skill requirements, restricted autonomy; low organizational status and
      estrangement from senior management. This proletarian class situation was
      reflected in an order taker's culture of informality, cynicism, hedonism and
      alienation. Since the late 1980s however technological change and workplace
      restructuring have markedly reduced the number of unskilled and lower paid jobs
      in the APS, thereby belying widespread predictions of deskilling. I conclude that
      proletarianization is more likely to have arisen from a decline in the status of
      clerical work during the course of the twentieth century rather than from a
      process of deskilling. Notwithstanding the fact that their class situations were
      predominantly proletarian, most clerks have identified as middle class. We can
      attribute this not only to the fact that their class situations differ from those
      of manual workers, as noted by Lockwood, but also to a widespread tendency to
      identify as middle class, the tendency of many female clerks to base their class
      identity on their husband's occupation and the fact that popular stereotypes tend
      to equate class with occupation. It is difficult to decide if clerks are
      proletarian since 1. Their class situations display a mixture of proletarian and
      middle-class characteristics 2. They exhibit diverse class identities, social
      origins, marriage partners and cultural attributes and 3. They occupy different
      positions on different aspects of inequality. We are therefore unable to allocate
      them en bloc to a single uniform class. I conclude that while a minority of
      clerks are proletarian most are better described as middle class.

PMID- 18076388
TI  - Religious individualization or secularization? Testing hypotheses of religious
      change--the case of Eastern and Western Germany.
AB  - The individualization thesis advanced by sociologists of religion such as Grace
      Davie, Daniele Hervieu-Leger, Michael Kruggeler, Thomas Luckmann, Hubert
      Knoblauch, Wade Clark Roof, Wayne E. Baker, and others has become increasingly
      widespread especially in Europe within the sociology of religion. In contrast to
      the secularization theory it assumes that processes of modernization will not
      lead to a decline in the social significance of religion, but rather to a change
      in its social forms. According to the individualization theory, traditional and
      institutionalized forms of religiosity will be increasingly replaced by more
      subjective ones detached form church, individually chosen, and syncretistic in
      character. The article examines the empirical applicability of the
      individualization thesis on the basis of how religiosity and church affiliation
      have evolved in Germany over the past 50 years. It comes to the conclusion that
      the rise of individually determined non-church religiosity cannot compensate for
      the losses of institutionalized religiosity, since non-church religiosity remains
      rather marginal and is interwoven with traditional Christian religiosity.
      Religious individualization is only a component of the predominant secularization
      process.

PMID- 18076389
TI  - An investigation into causal links between victimization and offending in
      adolescents.
AB  - There is a considerable body of evidence from earlier research to show that
      offending is associated with an increased risk of victimization, and being a
      victim with an increased risk of offending. There have been few earlier studies
      of the link. These have generally set out to test specific explanations, for
      example, the idea that the same lifestyles or routine activities may be
      associated with both victimization and offending. In a current study of a cohort
      of 4,300 adolescents in Edinburgh we have found a correlation of 0.421 between
      crime victimization and self-reported offending at the age of 15 when offending
      peaks. Variables chosen to test three broad types of theory - life-style and
      routine activities, weak social bonds, aspects of personality - are shown to be
      related both to victimization and to offending in adolescence. The present
      analysis uses latent class growth mixture models to track the dynamic
      relationships over time between adolescent victimization and offending both
      before and after controlling for these explanatory variables. In the short term,
      offending is strongly related to a later rise in victimization, but in the longer
      term to a fall that tends to cancel out the earlier rise. These findings remain
      the same after controlling for the ten explanatory variables. Victimization is
      associated with a later rise in offending in the longer term. The theoretical
      perspectives suggested by earlier researchers are fairly successful in explaining
      this linkage running from victimization to offending. Future research should
      focus on the role of peer influence in linking victimization and offending, and
      should push forward the analysis into the adult years. The implications for
      criminal justice policy could be far-reaching.

PMID- 18076390
TI  - The decline of British national pride.
AB  - This article examines how national pride has changed in Britain since the
      beginning of the 1980s. We show that there have been large declines in pride and
      that this is exclusively generational in nature; with more recent generations
      having substantially lower levels of pride in 'Britishness' than previous
      generations. Confirming the reality of 'Thatcher's Children', we find that this
      process has been arrested to some extent, with generations coming of age in the
      1980s and after having similar levels of pride to their immediate predecessors.
      We also find large regional disparities in these processes, with substantially
      bigger differences between new and old generations in Scotland, compared to
      England and Wales. Although generational differences in England and Wales appear
      to be generalized across a range of different aspects of nationhood that form
      citizens' national identity, generational differences in Scotland are more marked
      for certain types of national pride.

PMID- 18076391
TI  - Beyond class and nation: reframing social inequalities in a globalizing world.
AB  - From the start individualization theory is the investigation of the paradigm
      shift in social inequality. Furthermore it shows, how the transnationalization of
      social inequalities bursts the framework of institutional responses - nation
      state (parties), trade unions, welfare state systems and the national sociologies
      of social classes. In this essay I shall try to conceptually elucidate the
      'cosmopolitan perspective' on relations of social inequality in three cases: (1)
      the inequality of global risk; (2) the Europe-wide dynamic of inequality; and (3)
      transnational inequalities, which emerge from the capacities and resources to
      transcend borders. Before that I take up Will Atkinson's question: 'What exactly
      constitutes individualization and to what extent has it really displaced class?'
      (Atkinson 2007: Abstract).

PMID- 18076409
TI  - Public health training program of school employees--a pilot program.

PMID- 18076410
TI  - Can kindergartners help decrease inappropriate antibiotic use?

PMID- 18076411
TI  - Body mass index measurement in schools.
AB  - BACKGROUND: School-based body mass index (BMI) measurement has attracted much
      attention across the nation from researchers, school officials, legislators, and
      the media as a potential approach to address obesity among youth. METHODS: An
      expert panel, convened by the Centers for Disease Control and Prevention (CDC) in
      2005, reviewed and provided expertise on an earlier version of this article. The
      panel comprised experts in public health, education, school counseling, school
      medical care, and a parent organization. This article describes the purposes of
      BMI measurement programs, examines current practices, reviews existing research,
      summarizes the recommendations of experts, identifies concerns, and provides
      guidance including a list of safeguards and ideas for future research. RESULTS:
      The implementation of school-based BMI measurement for surveillance purposes,
      that is, to identify the percentage of students in a population who are at risk
      for weight-related problems, is widely accepted; however, considerable
      controversy exists over BMI measurement for screening purposes, that is, to
      assess the weight status of individual students and provide this information to
      parents with guidance for action. Although some promising results have been
      reported, more evaluation is needed to determine whether BMI screening programs
      are a promising practice for addressing obesity. CONCLUSIONS: Based on the
      available information, BMI screening meets some but not all of the criteria
      established by the American Academy of Pediatrics for determining whether
      screening for specific health conditions should be implemented in schools.
      Schools that initiate BMI measurement programs should evaluate the effects of the
      program on BMI results and on weight-related knowledge, attitudes, and behaviors
      of youth and their families; they also should adhere to safeguards to reduce the
      risk of harming students, have in place a safe and supportive environment for
      students of all body sizes, and implement science-based strategies to promote
      physical activity and healthy eating.

PMID- 18076412
TI  - Association of overweight with academic performance and social and behavioral
      problems: an update from the early childhood longitudinal study.
AB  - BACKGROUND: Childhood overweight is a condition that is prevalent within our
      society, affecting more and more children each year. The purpose of this study
      was to examine the relationship between child overweight and educational
      outcomes. METHODS: Data are reported for 13,680 children in third grade from the
      Early Childhood Longitudinal Study, a set of data designed and carried out by the
      US Department of Education. Students were individually administered reading and
      math assessments. Teachers reported how often students exhibited certain social
      skills and behaviors. A series of 1-way analyses of covariance and multivariate
      analysis of covariance was used. RESULTS: Overweight children had significantly
      lower math and reading test scores compared with nonoverweight children in third
      grade. However, these differences became insignificant after including
      socioeconomic and maternal education variables. Third grade overweight girls had
      significantly more externalizing and internalizing problems as well as lower self
      control scores than nonoverweight girls even after including socioeconomic and
      maternal education variables. CONCLUSIONS: Findings suggest that how we deal with
      children's overweight may have implications for the future psychological health
      of a considerable proportion of US children.

PMID- 18076413
TI  - Fruit and vegetable distribution program versus a multicomponent program to
      increase fruit and vegetable consumption: which should be recommended for
      implementation?
AB  - BACKGROUND: Two primary school-based interventions were implemented, aimed at
      increasing fruit and vegetable (F&V) consumption by children, both with proven
      effectiveness: (1) a free daily F&V distribution scheme for all primary school
      children and (2) a multicomponent, age-specific program consisting of a classroom
      curriculum, parental involvement, and an environmental component. This article
      describes and compares the implementation, evaluation, and potential for adoption
      of the 2 interventions. METHODS: A total of 48 teachers who worked with either of
      these programs filled out a questionnaire at the end of the intervention period.
      Additionally, 24 of the teachers who worked with the multicomponent program
      filled out periodic monitoring reports during the intervention. RESULTS: Compared
      to the F&V distribution, the multicomponent program was less fully implemented
      and that implementation of activities decreased over time. Both programs were
      evaluated favorably, and about half of the teachers indicated that they were
      willing to use the program again in the following school year. Teachers who used
      the multicomponent program experienced more social pressure to implement the
      program. They rated the program they had used as more complex and risky than the
      other group rated the distribution program. CONCLUSIONS: The free distribution
      program has the greatest potential for being adopted by schoolteachers, but that
      efforts must be made to acquire funding for it. Until these resources are
      available, the multicomponent program seems to be a good alternative if improved
      as suggested.

PMID- 18076414
TI  - Implementation of low-fat, low-sugar, and portion-controlled nutrition guidelines
      in competitive food venues of Maine public high schools.
AB  - BACKGROUND: The prevalence of childhood "overweight" and "at risk for overweight"
      has become a major public health concern. School food environments can affect key
      nutritional risk factors, especially in high schools where foods of poor nutrient
      value are pervasive in a la carte and vending programs. This study examines a la
      carte and vending programs in Maine public high schools at baseline and following
      implementation of low-fat (defined as items<or=30% of total calories from fat),
      low-sugar (defined as items<or=35% of sugar by weight), and portion-controlled
      (LFLS) guidelines. METHODS: Four high schools implemented LFLS guidelines and 3
      made no changes to a la carte and vending programs for a period of 1 school year.
      RESULTS: Findings revealed no significant change in food and beverage offerings
      in control schools. Whereas, in intervention schools, the proportion of items
      meeting the LFLS nutrient criteria increased from 32.8% to 81.8% in a la carte
      items, increased from 22.5% to 84.0% in snack vending, and increased from 48.0%
      to 98.9% in beverage vending from baseline to follow-up. However, these increases
      were mitigated when LFLS portion size criteria were applied. CONCLUSIONS: These
      findings demonstrate the successful implementation of LFLS guidelines similar to
      recommendations recently proposed by numerous organizations. School food service
      personnel were identified as key stakeholders in the successful implementation of
      the LFLS guidelines. Furthermore, these findings emphasize an important role the
      food and beverage industry will have in providing foods and beverages that meet
      proposed nutrient and portion guidelines.

PMID- 18076415
TI  - School food practices of prospective teachers.
AB  - BACKGROUND: Schoolteachers can affect students' eating habits in several ways:
      through nutrition knowledge, positive role modeling, and avoidance of unhealthy
      classroom food practices. In this study, the knowledge, attitudes, and eating
      behaviors of prospective teachers as determinants of intended classroom food
      practices and the school environment and its potential impact on classroom food
      practices were examined and explored. METHODS: One hundred and three students
      (response rate 79%) enrolled in the final year of a bachelor of education program
      with at least 22 weeks of practice teaching completed a self-administered
      questionnaire adapted from the Teens Eating for Energy and Nutrition at School
      teaching staff survey. Indexes related to classroom food practices, school food
      environment, personal health, fat intake, and nutrition knowledge were
      constructed and explored quantitatively using linear modeling techniques and
      contingency table analysis. RESULTS: The majority of respondents reported a high
      fat intake (65%) and had mid-to-low nutrition knowledge (72%). While most
      respondents (93%) believed that a healthy school food environment was important,
      two thirds reported unhealthy classroom food practices. Unhealthy classroom food
      practices were more likely to be used by those intending to teach at the
      secondary level, those who held a high personal health belief, and those who
      demonstrated less support for a healthy school environment. CONCLUSIONS: These
      findings suggest that knowledge, attitudes, and food behaviors of prospective
      teachers may be barriers to promoting healthy food habits to their future
      students. Further, prospective teachers would benefit from policies and programs
      that support healthy classroom practices and from compulsory nutrition education
      in the teacher training curriculum.

PMID- 18076416
TI  - The national school lunch and competitive food offerings and purchasing behaviors
      of high school students.
AB  - BACKGROUND: Across the nation, schools have become actively involved in
      developing obesity prevention strategies both in classrooms and in cafeterias. We
      sought to determine the type of foods being offered during lunch in the cafeteria
      of 3 public high schools in 1 county and if this reflects the purchasing patterns
      of students. By labeling foods based on nutrient density using a stoplight
      approach of green, yellow, and red colors, we were able to categorize all foods
      including the National School Lunch Program (NSLP) and competitive foods
      available in the cafeteria. METHODS: Over a 4-week cycle, daily food purchases
      were gathered and the proportions of green, yellow, and red foods offered and
      purchased was compared. RESULTS: Findings from this study suggest that students
      in these 3 high schools purchased foods in relative proportion to what was
      available in the school cafeteria for the NSLP. Green and yellow foods included
      in the NSLP comprised 77% of the offerings and 73% of the purchases. In contrast,
      61% of the competitive foods were classified as red foods, and the purchasing of
      red foods made up 83% of competitive food sales. These results indicate that
      students purchase foods of minimal nutritional value at greater proportions in
      the school cafeteria. CONCLUSIONS: These results suggest that the nutritional
      policy for the NSLP promotes the offerings of a wide array of foods. Schools
      should consider a nutrition policy that regulates the sale of competitive foods.

PMID- 18076417
TI  - Lessons learned while implementing a legislated school policy: body mass index
      assessments among Arkansas's public school students.
AB  - BACKGROUND: To comprehensively address the childhood and adolescent obesity
      epidemic, Arkansas enacted Act 1220 of 2003. Among a series of community- and
      school-based interventions, the Act requires each public school student to have
      his/her body mass index (BMI) assessed and reported annually to parents. The
      process of implementing this policy on a statewide level and lessons learned are
      described in this article. METHODS: A confidential, standardized protocol to
      measure student BMIs and report results to parents was developed. Affordable,
      reliable, and durable equipment was selected and school personnel who conducted
      BMI assessments were trained to ensure standardization. To enhance the efficiency
      and ease of the measurement and reporting process and promote long-term and
      locally based sustainability, during the first 3 years of implementation, a
      transition from a paper-based system to a Web-based system was made.
      Confidential, individualized Child Health Reports have provided students' parents
      with information about the health of their children. RESULTS: Participation by
      schools and students has been high as a result of collaboration between the
      health and education communities and the students and their families. Childhood
      obesity has not increased since Act 1220 was passed into law. CONCLUSIONS:
      Parents, schools, school districts, and the state are able to better understand
      the obesity epidemic and track progress using detailed annual data. Providing a
      standardized measurement protocol, equipment, and efficient data entry and report
      generation options has enabled Arkansas to institutionalize the BMI assessment
      process in public schools.

PMID- 18076419
TI  - Influence of genital heat stress on semen quality in humans.
AB  - The concept that an elevation of testicular temperature results in impairment of
      spermatogenesis is widely accepted. Here, current knowledge concerning genital
      heat stress and its consequences in men is reviewed. Duration of sitting during
      work positively correlates with daytime scrotal temperatures and daytime scrotal
      temperature negatively correlates with semen quality. However, the assumed
      negative correlation between duration of sitting and semen quality could not be
      shown in the available studies. Fertility parameters of professional drivers with
      long periods of sitting in vehicles were impaired; however, for predominantly
      affected drivers of vans, trucks or industrial heavy machinery potential
      confounders have to be considered. Wearing tight fitting compared with loose
      fitting underwear is associated with significantly higher scrotal temperatures.
      However, available observations suggesting a link between tight-fitting underwear
      or trousers and impaired semen quality are not convincing. Studies addressing
      professional exposure to high temperatures delivered conflicting results
      concerning fertility parameters. The postulated negative impact of sauna visits
      on semen quality is not sufficiently underlined by the available studies.
      Oligozoospermic men with a varicocele have significantly higher scrotal
      temperatures than normozoospermic men, and according to several studies
      varicocelectomy normalises scrotal temperatures. A further link has been reported
      between fever and deteriorated semen quality. Contraception via genital heat
      stress has been demonstrated using hot sitting baths or insulating suspensors.
      However, down-regulation of spermatogenesis is inconsistent and unsafe. On the
      other hand, scrotal and consecutively testicular cooling is able to improve semen
      quality.

PMID- 18076420
TI  - Safety aspects of androgen treatment with 5alpha-dihydrotestosterone.
AB  - 5alpha-Dihydrotestosterone (DHT), the most powerful naturally occurring androgen,
      is commercially available since 1982 as a gel. In view of its considerably higher
      biopotency (three to six times) than of testosterone, side effects, particularly
      on the main target organ of androgens, the prostate, are anticipated. In fact,
      DHT appears to be a prostate-sparing androgen for two reasons. Unlike
      testosterone, it does not undergo any further amplification in biopotency through
      5alpha reduction in the prostate. Secondly, it is likely to lead to less
      aromatisation of testosterone to oestradiol in the prostate, thus reducing local
      oestradiol concentrations. Oestrogens have been implicated in the aetiology of
      benign prostate hyperplasia and prostate cancer. However, aromatisation of
      testosterone has appeared to be essential for the maintenance of bone mineral
      density. Administration of DHT reduces circulating oestradiol levels, but the
      levels remain above the levels critical for the antiresorptive effect of
      oestrogens on bone. Effects of DHT on erythropoiesis and on lipids are very
      similar to those of testosterone. Safety concerns regarding androgen treatment
      with DHT are similar to those of treatment with testosterone, while the effects
      of DHT on the prostate are likely to be less biopotent.

PMID- 18076421
TI  - Lack of association between polymorphisms in p53 gene and spermatogenetic failure
      in a Chinese population.
AB  - Although various genetic factors have been demonstrated in human male
      infertility, many genetic causes involving gene variants for the idiopathic male
      infertility have not yet been elucidated. P53 gene is involved in the meiosis of
      the male rat and mice, which suggested that p53 plays a critical role in
      spermatogenesis. To examine whether the codon72 polymorphism and IVS7+72C>T
      polymorphism of the human p53 gene are associated with spermatogenetic failure in
      Han-Chinese population. A case-control study was conducted with 198 idiopathic
      infertile patients with nonobstructive azoospermia or severe oligozoospermia and
      233 fertile controls. We genotyped the two polymorphisms, codon72 and IVS7+72C>T,
      using polymerase chain reaction-restriction fragment length polymorphism assay.
      The polymorphisms were identified in both infertile patients and fertile
      controls. The allele and genotype frequencies of the two polymorphisms were not
      significantly different between the patients and controls. Further analysis
      showed that there was no statistically significant difference in the haplotype
      distributions between the patients and controls. The results of this study
      suggest that the codon72 and IVS7+72C>T polymorphisms of the p53 gene are
      unlikely to contribute to the pathogenesis of idiopathic male infertility with
      spermatogenetic failure.

PMID- 18076422
TI  - Sperm ultrastructure and meiotic segregation in an infertile 47, XYY man.
AB  - The majority of 47, XYY males are fertile and contribute to produce chromosomally
      normal children. In 47, XYY carriers, most meiotic studies indicated that the
      extra Y chromosomes were lost in the pre-meiotic stages, but in some cases the
      presence of one X and the two Y chromosomes has been detected during prophase I
      as an X univalent plus a YY bivalent. The aim of this study was to describe sperm
      parameters and meiotic segregation in a case of an infertile man with a 47, XYY
      karyotype. Sperm morphology was evaluated for the first time by transmission
      electron microscopy highlighting apoptosis and necrosis as the most frequent
      pathologies. Meiotic segregation was explored by fluorescence in situ
      hybridisation technique, which makes us capable of detecting aneuploidies of sex
      chromosomes. The fact that the frequency of 1818XY diploidy was very high reveals
      an error occurring during first meiotic division. Polymerase chain reaction
      analysis did not show any Y microdeletion. The combination of these two
      techniques led us to clarify the status of the spermatogenic process, showing an
      altered meiotic segregation concomitant with the presence of sperm apoptosis and
      necrosis in a patient 47, XYY.

PMID- 18076423
TI  - Evaluation of antiandrogenic potentials of aqueous extract of Chromolaena
      odoratum (L.) K. R. leaves in male rats.
AB  - The antiandrogenic effect of oral administration of aqueous extract of
      Chromolaena odoratum leaves (250 and 500 mg kg(-1) body weight) for 14 days in
      male albino rats was investigated. Forty-two white albino rats were randomly
      divided into three groups: A, B and C. Group A which served as the control
      received 1 ml of distilled water (the vehicle) twice daily for 14 days, whereas
      groups B and C were treated in the same way like the control except that the
      animals received 250 and 500 mg kg(-1) body weight of the plant extract
      respectively. Compared with the control, extract administration at 250 and 500 mg
      kg(-1) body weight revealed a significant reduction (P<0.05) in testicular body
      weight ratio, acid phosphatase activities, protein, cholesterol, glycogen, sialic
      acid and testosterone concentrations with a significant increase (P<0.05) in
      lactate dehydrogenase and gamma-glutamyl transferase activities. There was no
      significant change (P>0.05) in serum concentrations of follicle stimulating and
      luteinising hormones. Histological examination revealed disruption in the
      arrangement of seminiferous tubules with no distinct basement membrane. These
      changes were accompanied by reduction in the number of spermatozoa. All these
      results indicated that aqueous extract of C. odoratum leaves possesses
      antiandrogenic property by interfering with steroidogenesis at the testicular
      level and this will adversely affect the functional capacity of the testes and
      the fertility of the animal.

PMID- 18076424
TI  - Seminal mast cells in infertile asthenozoospermic males.
AB  - This work aimed to assess the possible association between the presence of
      seminal mast cells and asthenozoospermia. One hundred and seventy-six male
      subjects were investigated: group (Gr)1 (n=46) normozoospermic fertile controls,
      Gr2 (n=62) idiopathic asthenozoospermia, Gr3 (n=32) asthenozoospermia with
      scrotal varicocele and Gr4 (n=36) asthenozoospermia with leucocytospermia. Four
      smear slides were prepared for each semen sample to be stained with toluidine
      blue-pyronin to detect mast cells. A significant increase was shown in mast cell
      positive samples among varicocele-associated and idiopathic asthenozoospermic
      patients in comparison with fertile controls. Seminal mast cells were also
      detected at higher frequency among smokers and in age group over 40 years. It is
      concluded that mast cells and their products may play a pivotal role in the
      pathogenesis of asthenozoospermia, possibly proposing a new goal for medical
      treatment of infertile males to pursue. In addition, this concept may in a way
      detain smoking as a cause of male infertility considering the clear abundance of
      mast cells in semen samples of smokers.

PMID- 18076425
TI  - Psychotherapy and transsexualism.
AB  - We questioned whether transsexuals always require the psychotherapy demanded by
      the health insurance system in Germany. For this purpose, we examined 430
      transsexuals who came to our facility between 1988 and 2006. At the first
      consultation after the history was taken, they filled out standardised
      questionnaires, which are needed for proper diagnosis of psychotherapeutic
      treatment. These questionnaires included the Complaint Questionnaire (BFB), the
      Behaviour Questionnaire (VFB) and the Freiburg Personality Inventory (FPI-A). It
      was found that two-thirds of all transsexuals do not require deeper
      psychotherapy. However, there was evidence of personality deficits in a subgroup
      of transsexuals for whom supportive psychotherapy should be recommended. The
      conditions under which psychotherapy and other forms of support are successful
      are discussed.

PMID- 18076426
TI  - Secretion of testicular steroids and gonadotrophins in hypothyroidism.
AB  - Inconsistent alterations in gonadal steroidogenesis and pituitary functions have
      been reported in hypothyroid males. We have compared the lipid and endocrine
      profiles of the euthyroid and hypothyroid [thyroid-stimulating hormone (TSH) >100
      mIU l(-1)] males. Hypothyroidism was found to be associated with an increase in
      the circulating level of total cholesterol and LDL-cholesterol (LDL-C) and a
      reduction in the levels of progesterone and testosterone, without any change in
      the serum levels of oestradiol and gonadotrophins. The failure of gonadotrophins
      to rise could be accounted by a normal level of serum oestradiol in the
      hypothyroid male. A mild hyperprolactinaemia was also noted in the hypothyroid
      patients. The reduction in serum testosterone level could be explained by (i) a
      reduced uptake of LDL-C by the Leydig cells and thereby a reduction in the
      synthesis of progesterone and consequentially testosterone, (ii) a further
      reduction in the rate of conversion of progesterone to testosterone, (iii) a
      higher rate of conversion of testosterone to oestradiol, (iv) a decrease in serum
      triiodothyronine and (v) hyperprolactinaemia. Rise in TSH needs to be
      investigated as a cause of the suppression of gonadal steroidogenesis.

PMID- 18076427
TI  - A case report on idiopathic recurrent priapism.
AB  - Idiopathic recurrent priapism is a difficult problem to treat and a potentially
      devastating condition that may result in irreversible penile fibrosis. We present
      the case of a patient who, during a period of 10 years, had recurrent episodes of
      idiopathic priapism and we show that therapeutic options do exist for the
      management.

PMID- 18076428
TI  - Psychometric qualities of questionnaires for the assessment of otitis media
      impact.
AB  - BACKGROUND: The assessment of impact and evaluation of treatment effects in
      chronic otitis media (OM) calls for a much broader approach than just examining
      the presence of middle ear effusion or hearing loss. It is increasingly
      recognised that this condition may result in a comprised quality of life. Several
      studies have used proxy completed questionnaires to objectify the illness
      experience associated with chronic OM. OBJECTIVE OF REVIEW: To review
      questionnaires which have been developed to describe the effects of chronic OM on
      the daily functioning of children. Psychometric properties have been evaluated,
      in addition to discriminative and evaluative qualities. TYPE OF REVIEW: A
      systematic review of publications pertaining to developed questionnaires related
      with chronic OM. SEARCH STRATEGY: Systematic literature searches of PubMed (1966
      January 2007) and EMBASE (1989-January 2007) were conducted, supplemented by
      using free text words to identify publications after January 2005. RESULTS: The
      included 15 questionnaires were developed for children with recurrent or
      persistent OM, describing functional health status (FHS), while two
      questionnaires also evaluate the effect of tympanostomy tubes insertion. The
      questionnaires generally cover six impact areas (physical symptoms, child
      development, educational performance, emotional/practical burden and general
      health status) with physical symptoms being the most prominant. CONCLUSIONS: The
      OM8-30, OMO-22 and OM-6 adequately reflect the multidimensional aspects of FHS in
      chronic OM. The OMO-22 and OM8-30 show the best psychometric properties for the
      discrimination of impact severity between children, while the OM-6 was found to
      have the best qualities for the evaluation of clinical change. Clinical
      applicability is crucial for the assessment of FHS in chronic OM, but requires a
      trade-off with necessary psychometric properties.

PMID- 18076429
TI  - Symptoms experienced by patients with peripheral vestibular disorders: evaluation
      of the Vertigo Symptom Scale for clinical application.
AB  - OBJECTIVES: To describe symptoms during an episode of dizziness in a sample of
      patients suffering from peripheral vestibular disorders and to compare them with
      the items in the Vertigo Symptom Scale. DESIGN: A descriptive study from a sample
      of patients with peripheral vestibular disorders. SETTING: Patients visiting a
      department of audiology at a university hospital. PARTICIPANTS: Twenty patients
      with peripheral vestibular disorders. The inclusion criteria were that the
      patient had had at least three spontaneous attacks of vertigo and/or was
      constantly unsteady during the last 3 months for at least 75% of the time when
      awake. MAIN OUTCOME MEASURES: Patients were instructed to complete a diary where
      they recorded symptoms that arose during an episode of dizziness. These symptoms
      were compared with the content of the Vertigo Symptom Scale. RESULTS: The most
      frequent symptoms as mentioned by the patients in their diaries were a feeling
      that things are spinning or moving around, nausea, feeling unsteady/about to lose
      one's balance, fatigue, headache, a feeling as if the ground you walk on is
      distant and ear-related such as tinnitus and a feeling of pressure in the ear.
      Pain in the heart or chest region, a heavy feeling in the arms or legs, pain in
      the lower part of the back and excessive sweating were not mentioned at all or by
      very few patients. Analysis showed that some of the symptoms included in the
      Vertigo Symptom Scale occurred less during an episode of dizziness than others in
      this sample of patients with peripheral vestibular disorders. CONCLUSION: It was
      found that the Vertigo Symptom Scale is an adequate base but may need to be
      developed for use in patients diagnosed with peripheral vestibular symptoms to be
      able to evaluate care and treatment.

PMID- 18076430
TI  - Salvage optic nerve decompression for traumatic blindness under nasal endoscopy:
      risk and benefit analysis.
AB  - OBJECTIVES: Transnasal endoscopic optic nerve decompression was recommended to
      treat traumatic optic neuropathy as an effectively adjunctive procedure. The aim
      of this study was to assess the risks and benefits of salvage surgical
      decompression for complete vision loss (no light detection) after failure of mega
      dose steroid therapy. DESIGN: Retrospective study. SETTING: Two hospitals in
      Guangzhou and Nanjing, China. PARTICIPANTS: Forty-two patients of traumatic optic
      neuropathy with complete vision loss and failed to improve after steroid therapy
      for at least 3 days. MAIN OUTCOME MEASURES: All patients were treated by
      transnasal endoscopic optic nerve decompression and received follow-up for at
      least 6 month. Vision improvement and complications were evaluated. RESULTS:
      Transnasal endoscopic optic nerve decompression was performed successfully in 40
      patients and was incomplete in two patients due to bleeding. Vision improved in
      four of 42 patients (9.5%) of traumatic optic neuropathy with complete vision
      loss and failed steroid therapy. Complications and sequelae included severe
      bleeding (two cases), cerebrospinal fluid rhinorrhea (one case), nasal polyps
      (seven cases), chronic sinusitis (four cases) and nasal synechia (17 cases).
      CONCLUSION: Transnasal endoscopic optic nerve decompression was recommended as a
      minimally invasive, safe procedure, but complications and sequelae of the surgery
      should not be neglected. Based on the risk and benefit analysis, we conclude that
      the very poor surgical outcomes of this series do not support endoscopic optic
      nerve decompression for traumatic blindness.

PMID- 18076431
TI  - Globus sensation as early presentation of hypopharyngeal cancer.
AB  - OBJECTIVES: To identify if patients with early hypopharyngeal carcinoma can
      present with only the single complaint of globus sensation. DESIGN: Retrospective
      case review. SETTING: Teaching Hospital in Scotland. PARTICIPANTS: Cohort of 23
      patients with hypopharyngeal carcinoma. Retrospective review of their case notes
      with regards to their hospital pathway from initial referral from the General
      Practitioner to diagnosis. OUTCOME MEASURES: Symptoms & signs on presentation,
      subsequent investigations and time interval between initial presentation and
      diagnosis. RESULTS: We identified two patients (9%) who presented early with
      globus or other soft symptoms as the only complaint and with normal clinical
      findings. There was a 78%'pick up' rate of abnormalities in the barium swallow
      examination. CONCLUSION: We believe this can have important clinical implications
      in the screening & investigation of globus patients who represent a significant
      outpatient workload. We review the relevant literature.

PMID- 18076432
TI  - Otitis externa.

PMID- 18076435
TI  - Endoscopic dewaxing in the audiology department--the Bristol experience.
AB  - Impacted wax accounts for a considerable proportion of cancelled appointments in
      the audiology department. Current practice usually involves the patient being
      referred back to their General Practitioner (GP) for wax removal. Endoscopic
      dewaxing is a technique that can be used to remove wax under direct vision.
      Having been trained in the technique, an audiologist successfully removed wax
      from 94% of the patients seen with wax preventing the appointment from going
      ahead. Thirty-three appointments and 29 h (1740 min) of appointment time were
      saved over the 6-week period. When introduced with sufficient training of staff,
      endoscopic dewaxing offers a solution to the problem of impacted wax in the
      audiology department.

PMID- 18076436
TI  - Extracorporal septal reconstruction with polydioxanone foil.
AB  - Conventional septoplasty cannot be the answer to all types of septal deviation.
      Indications of extracorporal septal reconstruction with polydioxanone (PDS) foil:
      (i) selected cases of very high septal deviations, (ii) post-traumatic and (iii)
      extremely pronounced congenital septal deviations and/or aesthetic deformities.
      Polydioxanone foil facilitates the incorporation of a newly implanted septal
      graft without significant postoperative complications and is absorbed within 25
      weeks. The surgical technique is described in detail, and the early postoperative
      functional and aesthetic results (mean follow-up: 11 months) on 16 patients (mean
      age: 42 years) are reported. Overall, 88% of the patients responded positively to
      the question of whether they would choose to undergo the same procedure again,
      knowing the postoperative result. The procedure is easy to learn and has already
      proved to be an excellent combination of modern functional and aesthetic nasal
      surgery.

PMID- 18076437
TI  - Results of endoscopic tracheoplasty for treating tracheostomy-related airway
      stenosis.
AB  - Post-tracheostomy 'lambdoid' deformity of the trachea is a specific and uncommon
      variant of adult post-intubation laryngotracheal stenosis, in which airway
      obstruction is caused by inward collapse of over-resected tracheal cartilage as a
      result of post-decannulation stomal contracture. We evaluated the results of
      endoscopic tracheoplasty as an alternative to open tracheal resection in 11
      patients treated for this condition between 2004 and 2006. Patients were treated
      with endoscopic CO(2) laser resection, dilatation and endotracheal mitomycin C
      application. Suspension micro-laryngo-tracheoscopy and high-frequency
      supraglottic jet ventilation were used. Eleven patients with an average age of 56
      years and lesion height and distance from glottis respectively of 11 +/- 5 mm and
      35 +/- 12 mm were treated. The median number of treatments fell from four at the
      start of the series to two at the end (P = 0.08). The average follow-up was 17 +/
      8 months and all patients were cured with no cases of dysphagia or dysphonia.
      Almost all patients achieved and maintained a Medical Research Council Dyspnoea
      Scale of I or II. Endoscopic tracheoplasty is an effective treatment for this
      condition. It achieves a successful outcome while avoiding the operative risks,
      prolonged hospitalisation, and morbidity that is associated with tracheal
      resection. We recommend it as the standard of care for treating patients with
      this injury.

PMID- 18076438
TI  - Objective assessment of surgical competency--ENT trainees.
AB  - The objective assessment of the progression of surgical competence throughout the
      career of a trainee surgeon is complicated. An operative competence assessment
      form was introduced into the RITA process for ENT trainees in 2004 in the Eastern
      Deanery. Analysis of the data has shown that there is a clear improvement in
      their surgical ability with 'minor' procedures being mastered much earlier in
      their career than 'major' procedures. The value of such an assessment tool is
      that it has the potential to identify the trainee that has poor surgical ability
      early and it also provides evidence that senior trainees at the end of their
      training are surgically competent to meet the demands of a consultant post.

PMID- 18076439
TI  - Silicone Foley catheters outperform latex Foley catheters for post-nasal packing:
      an in-vitro study.
AB  - OBJECTIVES: To determine the best Foley catheter and inflation fluid for post
      nasal packing. DESIGN: Experimental study. SETTING: District General Hospital
      (Wexham Park Hospital). MATERIALS: 108 latex and 108 silicone catheters were
      directly compared. OUTCOME MEASURES: Catheters were analysed according to the
      inflation fluid instilled and the use of an umbilical clamp. Analysis occurred at
      24, 36, 48 and 72 h periods after being placed in humidified incubator at 37
      degrees C. The main outcome measure was whether deflation was possible at
      specified times. The secondary outcome measure was an attempt to identify the
      failure point in those catheters that failed to deflate. RESULTS: Air was found
      to be an unsuitable inflation fluid for either silicone or latex catheters due to
      a 100% spontaneous deflation rate within a 24-h period. Silicone catheters were
      found to be 100% reliable when inflated with water or saline, irrespective of the
      use of a clamp. Latex catheters were unreliable with an overall failure rate of
      30%. This high failure rate was related both to the use of an umbilical clamp to
      secure the catheter and to the use of saline as the inflation medium. CONCLUSIONS
      AND RECOMMENDATIONS: Firstly, air should not be used for inflation of catheters
      unless specified in manufacturer's instructions. Secondly, when Foley catheters
      are used for post-nasal packing, silicone should be considered the first choice
      of catheter type. If not available, latex ones may be used but should be inflated
      with water and secured with a non-crushing clamp at the alar rim.

PMID- 18076440
TI  - Comorbidity in nasopharyngeal carcinoma: a preliminary communication on the
      prevalence, descriptive distribution and impact on outcome.
AB  - OBJECTIVES: Comorbidity has been shown to be a determinant in treatment selection
      and survival in squamous cell cancer of the head and neck at various subsites.
      The objective of this study is to analyse the effect of comorbidity burden on
      outcome of nasopharyngeal cancer using the Adult Comorbidity Evaluation-27 (ACE
      27) instrument. DESIGN: Retrospective analysis. SETTING: Tertiary care centres.
      PARTICIPANTS: This study included 59 patients diagnosed with nasopharyngeal
      carcinoma between 1989-2003 in the North-East of England. Exclusion criteria
      included non-squamous neoplasms of the nasopharynx. Comorbidity was assessed
      retrospectively from the notes using standard validated techniques described
      earlier. Tumour, treatment and survival data were obtained from prospective
      databases. Data was analysed using SPSS for Windows. MAIN OUTCOME MEASURES:
      Comorbidity and outcome of treatment. RESULTS: Comorbid burden was evident in 44%
      of patients, with moderate or severe comorbidity in 19%. The cardiovascular
      system was the most commonly affected system (27%). Cox's proportional hazard
      model showed age and stage of tumour to have an impact on disease specific
      survival. Comorbidity was not seen to predict the outcome independent of other
      factors. The sample size of this study is powered to detect only medium to large
      effects. We estimate that 614 subjects will be needed to detect a correlation
      coefficient of 0.1 with 80% power, assuming a type 1 error rate of 5%.
      CONCLUSION: This study shows for the first time that the comorbidity burden seen
      in nasopharyngeal cancer does not affect prognosis independent of the TNM
      staging.

PMID- 18076441
TI  - Comparison between two valsalva techniques for improvement of hypopharyngeal
      nasendoscopy: a preliminary communication.
AB  - OBJECTIVE: To compare the nasal valsalva with the trumpet manoeuvre and anterior
      neck skin traction as aids to nasendoscopic examination of the hypopharynx.
      DESIGN: Randomised, controlled comparison of examination techniques. SETTING:
      Single tertiary referral centre. PARTICIPANTS: Twenty-six adult patients
      requiring hypopharyngeal nasendoscopic examination were recruited. Patients were
      examined with both techniques in a randomised order that was recorded to video
      cassette. MAIN OUTCOME MEASURES: Blinded assessment of the percentage
      visualisation of the pyriform fossae, post-cricoid and upper oesophageal
      sphincter was carried out by three consultant otolaryngologists independently.
      RESULTS: Mean percentage scores (and 95% confidence intervals) for nasal valsalva
      versus trumpet manoeuvre for the three consultants, respectively, were as
      follows: right pyriform fossa: 77(68, 87) versus 80(71, 91), 61(55, 66) versus
      60(54, 66), 46(38, 54) versus 45(37, 54); left pyriform fossa: 76(65, 87) versus
      80(69, 91), 59(53, 64) versus 55(49, 61), 42(35, 49) versus 42(35, 50); post
      cricoid: 55(44, 67) versus 59(47, 71), 53(46, 60) versus 53(46, 60), 32(25, 39)
      versus 32(25, 39); upper oesophageal sphincter: 11(1, 21) versus 21(11, 31),
      15(9, 21) versus 20(14, 26), 4(0, 8) versus 7(3, 11). No significant difference
      was found between the two techniques at any subsite. Individual differences were
      noted in a minority of patients where one or other technique gave a clearly
      improved view. CONCLUSIONS: The nasal valsalva and the trumpet manoeuvre with
      anterior neck skin traction are complementary techniques for improving the view
      of the hypopharynx.

PMID- 18076443
TI  - Indirect laryngoscopy--the cold way.

PMID- 18076444
TI  - Masters degrees for ENT trainees.

PMID- 18076445
TI  - Masters degrees for ENT trainees.

PMID- 18076446
TI  - A pilot randomised controlled trial of coblation tonsillectomy versus dissection
      tonsillectomy with bipolar diathermy.

PMID- 18076447
TI  - A possible age effect influencing epistaxis admissions in Asians versus
      Caucasians.

PMID- 18076448
TI  - Documenting telephone advice.

PMID- 18076449
TI  - Dizziness and anxiety.

PMID- 18076450
TI  - A simple and inexpensive technique of recording operative microscopic and
      endoscopic video directly to your computer.

PMID- 18076451
TI  - Use of image guidance in endoscopic sinus surgery.

PMID- 18076452
TI  - Hands free endoscopic transnasal choanal atresia surgery.

PMID- 18076453
TI  - Nasal fracture manipulation under local anaesthetic without injections.

PMID- 18076454
TI  - A technique for trans-lingual biopsy of the tongue base.

PMID- 18076455
TI  - Otolaryngology bibliometry--is there a regional variation in the United Kingdom?

PMID- 18076456
TI  - The Moffett's mister: a reliable method of topical preparation of the nose.

PMID- 18076457
TI  - Effective visualisation of small and mildly radio-opaque foreign bodies in the
      aero digestive tract--picture archiving and communication systems.

PMID- 18076460
TI  - Carrots, sticks and sermons: is feedback the answer to changing clinicians'
      behavior?

PMID- 18076461
TI  - Incontinence: assessment, diagnosis, and management in two rehabilitation units
      for older people.
AB  - BACKGROUND: Incontinence of both bladder and bowel is a major health care problem
      and adversely affects the lives of many people living at home or in health
      service facilities. The prevalence and severity of incontinence is a global
      concern that has, in recent years, prompted investigation across several
      countries. Current approaches to continence care indicate an emphasis on safety
      and reduction of risk, rather than on detailed individualised assessment and
      management. AIM: To show approaches to assessment, diagnosis, and management of
      urinary and faecal incontinence in two rehabilitation settings for older people
      in Ireland. The study forms part of a larger 2-year case study to identify the
      determinants of practice "context" that enable or hinder proactive approaches to
      promoting continence and the treatment of incontinence in rehabilitation settings
      for older people. METHOD: The Royal College of Physicians Audit Scheme was used
      to record the assessment and management of urinary and faecal incontinence. This
      scheme also includes questions regarding resources available to enable effective
      continence management. Over 6 months, 220 patients who suffered from incontinence
      participated in two study sites: a 78-bed rehabilitation unit in Northern Ireland
      and an 80-bed rehabilitation unit in Southern Ireland. RESULTS: Findings
      indicated that 60% of incontinent patients had urinary incontinence, 3% faecal
      incontinence, and 37% mixed urinary and faecal incontinence; however, a specific
      continence assessment and specific rationale for treatment decisions or
      continuation of care were lacking. The focus was on continence containment rather
      than on proactive management. The examination of resources available for
      continence promotion and management showed that even though guidelines for
      continence management were available to staff in one unit, there was a dearth of
      appropriate education or support for staff in continence care. IMPLICATIONS FOR
      PRACTICE: Because incontinence remains an issue for older people and the clinical
      implications of sustained incontinence are multifaceted, strategies should focus
      on the development of practice towards evidence-based multidisciplinary
      approaches to continence promotion and management.

PMID- 18076462
TI  - Evaluation of an evidence-based practice initiative: outcomes, strengths and
      limitations of a retrospective, conceptually-based approach.
AB  - BACKGROUND AND PURPOSE: Making evidence-based practice (EBP) a sustained reality
      is a difficult endeavor. This relates, among other factors, to lack of sufficient
      research upon which to base implementation efforts. Alternative sources of
      evidence therefore need to be considered, particularly where organizational level
      EBP is the goal. In this article a brief evaluation of a service-based initiative
      with the aim of obtaining insights regarding multiple types and levels of EBP
      related outcomes is described. METHODS: A structured, retrospective improvement
      evaluation was conducted. Semi-structured interviews and available documents were
      chosen to obtain information regarding outcomes, perceived spread of reported
      individual changes, and factors related to the degree of progress. Underlying the
      method is an evaluation model that shows a progressive set of EBP outcomes at
      both individual and group levels. FINDINGS: Evaluative results, although limited
      by several factors, provided credible and sufficient internal evidence for this
      organization's leadership team to build upon past efforts and refine their
      approach to integrating research utilization (RU) throughout the department of
      nursing. For example, the evaluation indicated a set of RU outcomes at the
      individual nurse level not previously considered and also indicated limitations
      and challenges to full achievement of initial project-related goals. DISCUSSION
      AND IMPLICATIONS: The evaluation provided suggestive internal evidence regarding
      potential benefits of one component of a long-term, valued EBP initiative.
      However, the evaluation also raised questions regarding structural aspects of
      this initiative; identified barriers to progress; provided information for
      dialogue and planning; and highlighted future needs for a proactive, systematic
      evaluation and a documented trail of data related to all EBP program goals. For
      those in settings with similar characteristics and aims that have not built in
      such a prospective evaluation for EBP initiatives, this evaluative project can be
      assessed for its applicability.

PMID- 18076463
TI  - Audit and feedback as a clinical practice guideline implementation strategy: a
      model for acute care nurse practitioners.
AB  - BACKGROUND: The transfer of research evidence into practice and changing provider
      behavior is challenging, even when the advantages are strong. Despite the
      availability of supportive care clinical practice guidelines (CPG), consistent
      integration of these principles into practice has not been achieved. The failure
      of dissemination strategies has been identified as a key barrier to successful
      implementation. A potentially effective approach to facilitating the transfer of
      research evidence into practice is audit and feedback. Audit and feedback is a
      summary of provider performance over a specified period of time, with or without
      recommendations to improve practice. RATIONALE: Cancer pain is an optimal symptom
      to examine when studying the effect of an audit and feedback intervention. It is
      a common condition with important consequences, established CPG are available,
      measurable outcomes are defined, and there is potential for improvement in
      current practice. Acute care nurse practitioners (NPs) are often responsible for
      overseeing and directly managing symptoms such as pain and are well positioned to
      implement CPG and study the effects of adherence to guidelines on patients' pain
      outcomes. METHODOLOGY: A systematic review of published articles, MEDLINE, the
      Cumulative Index to Nursing and Allied Health Literature, and the Cochrane
      Library computerized databases was performed to evaluate the state of the science
      on audit and feedback as a professional practice change strategy. A behavior
      change model is proposed for its application to advanced practice nursing.
      IMPLICATIONS FOR PRACTICE: Recognized in medicine as a valuable intervention to
      improve healthcare quality, audit and feedback is a strategy that has not been
      widely studied in nursing. Although cancer pain cannot always be entirely
      eliminated, appropriate use of available therapies can effectively relieve pain
      in a majority of patients. This article is a review of the literature on audit
      and feedback as a professional practice change strategy and indicates a model for
      operationalizing the intervention.

PMID- 18076464
TI  - Factors influencing best-practice guideline implementation: lessons learned from
      administrators, nursing staff, and project leaders.
AB  - BACKGROUND: Clinical practice guidelines are promising tools for closing the
      research evidence-practice gap, yet effective and timely implementation of
      guidelines into practice remains fragmented and inconsistent. Factors influencing
      effective guideline implementation remain poorly understood, particularly in
      nursing. A sound understanding of barriers and facilitators is critical for
      development of effective and targeted guideline implementation strategies. AIM:
      This paper reports the perceptions of administrators, staff, and project leaders
      about factors influencing implementation of nursing best practice guidelines.
      METHODS: Twenty-two organizations, in clusters of two to five, implemented one of
      seven guidelines in acute, community and long-term care settings. The topics were
      client centered care, crisis intervention, healthy adolescent development, pain
      assessment, pressure ulcers, supporting and strengthening families and
      therapeutic relationships. Fifty-nine administrators, 58 staff and 8 project
      leaders participated in post implementation semi-structured telephone interviews.
      Qualitative thematic analysis was conducted. FINDINGS: Factors at individual,
      organizational and environmental levels were identified as influencing guideline
      implementation. Facilitators included learning about the guideline through group
      interaction, positive staff attitudes and beliefs, leadership support, champions,
      teamwork and collaboration, professional association support, and inter
      organizational collaboration and networks. Barriers included negative staff
      attitudes and beliefs, limited integration of guideline recommendations into
      organizational structures and processes, time and resource constraints, and
      organizational and system level change. Similarities and differences in
      perceptions of these factors were found among staff, project leaders and
      administrators. IMPLICATIONS/CONCLUSIONS: Best practice guideline implementation
      strategies should address barriers related to the individual practitioner, social
      context, and organizational and environmental context, and should be tailored to
      different groups of stakeholders (i.e., nursing staff, project leaders and
      administrators). Health care administrators need to recognize the "real" costs
      and complexity associated with successful implementation of guidelines and the
      need to ensure corporate commitment at the onset.

PMID- 18076468
TI  - Genomic selection: marker assisted selection on a genome wide scale.

PMID- 18076469
TI  - Genomic selection.
AB  - Genomic selection is a form of marker-assisted selection in which genetic markers
      covering the whole genome are used so that all quantitative trait loci (QTL) are
      in linkage disequilibrium with at least one marker. This approach has become
      feasible thanks to the large number of single nucleotide polymorphisms (SNP)
      discovered by genome sequencing and new methods to efficiently genotype large
      number of SNP. Simulation results and limited experimental results suggest that
      breeding values can be predicted with high accuracy using genetic markers alone
      but more validation is required especially in samples of the population different
      from that in which the effect of the markers was estimated. The ideal method to
      estimate the breeding value from genomic data is to calculate the conditional
      mean of the breeding value given the genotype of the animal at each QTL. This
      conditional mean can only be calculated by using a prior distribution of QTL
      effects so this should be part of the research carried out to implement genomic
      selection. In practice, this method of estimating breeding values is approximated
      by using the marker genotypes instead of the QTL genotypes but the ideal method
      is likely to be approached more closely as more sequence and SNP data is
      obtained. Implementation of genomic selection is likely to have major
      implications for genetic evaluation systems and for genetic improvement
      programmes generally and these are discussed.

PMID- 18076470
TI  - Prediction of response to marker-assisted and genomic selection using selection
      index theory.
AB  - Selection index methods can be used for deterministic assessment of the potential
      benefit of including marker information in genetic improvement programmes using
      marker-assisted selection (MAS). By specifying estimates of breeding values
      derived from marker information (M-EBV) as a correlated trait with heritability
      equal to 1, it was demonstrated that marker information can be incorporated in
      standard software for selection index predictions of response and rates of
      inbreeding, which requires specifying phenotypic traits and their genetic
      parameters. Path coefficient methods were used to derive genetic and phenotypic
      correlations between M-EBV and the phenotypic data. Methods were extended to
      multi-trait selection and to the case when M-EBV are based on high-density marker
      genotype data, as in genomic selection. Methods were applied to several example
      scenarios, which confirmed previous results that MAS substantially increases
      response to selection but also demonstrated that MAS can result in substantial
      reductions in the rates of inbreeding. Although further validation by stochastic
      simulation is required, the developed methodology provides an easy means of
      deterministically evaluating the potential benefits of MAS and to optimize
      selection strategies with availability of marker data.

PMID- 18076471
TI  - Comparison of genomic and traditional BLUP-estimated breeding value accuracy and
      selection response under alternative trait and genomic parameters.
AB  - Accuracy of prediction of estimated breeding values based on genome-wide markers
      (GEBV) and selection based on GEBV as compared with traditional Best Linear
      Unbiased Prediction (BLUP) was examined for a number of alternatives, including
      low heritability, number of generations of training, marker density, initial
      distributions, and effective population size (Ne). Results show that the more the
      generations of data in which both genotypes and phenotypes were collected, termed
      training generations (TG), the better the accuracy and persistency of accuracy
      based on GEBV. GEBV excelled for traits of low heritability regardless of initial
      equilibrium conditions, as opposed to traditional marker-assisted selection,
      which is not useful for traits of low heritability. Effective population size is
      critical for populations starting in Hardy-Weinberg equilibrium but not for
      populations started from mutation-drift equilibrium. In comparison with
      traditional BLUP, GEBV can exceed the accuracy of BLUP provided enough TG are
      included. Unfortunately selection rapidly reduces the accuracy of GEBV. In all
      cases examined, classic BLUP selection exceeds what was possible for GEBV
      selection. Even still, GEBV could have an advantage over traditional BLUP in
      cases such as sex-limited traits, traits that are expensive to measure, or can
      only be measured on relatives. A combined approach, utilizing a mixed model with
      a second random effect to account for quantitative trait loci in linkage
      equilibrium (the polygenic effect) was suggested as a way to capitalize on both
      methodologies.

PMID- 18076472
TI  - Estimation of genome-wide haplotype effects in half-sib designs.
AB  - Genome-wide estimated breeding values can be computed from the simultaneous
      estimates of the effects of small intervals of DNA throughout the genome on a
      trait or traits of interest. Small intervals or segments of DNA can be created by
      the use of thousands of single nucleotide polymorphisms (SNP) available in panels
      of 10, 25 and 50 thousand SNP. A simulation study was conducted to compare
      factors that could influence the accuracy of genome-wide selection. Factors
      studied were the heritability of the trait, dispersion of quantitative trait loci
      (QTL) across the genome and size of the QTL effects. A 100-cM genome was assumed
      with 100 equally spaced SNP markers and 10 QTL. A granddaughter design was
      constructed with 20 sires and 100 sons per sire. Population-wide linkage
      disequilibrium was assumed to be sufficient after 25 generations of random mating
      starting with 30 sires and 400 dams. Best linear unbiased prediction was used to
      simultaneously estimate the effects of 99 SNP intervals, based on determining the
      SNP haplotype of each son inherited from the sire. Indicator variables were used
      in the model to indicate haplotype transmission. A genome-wide estimated breeding
      value was calculated as the sum of the appropriate haplotype interval estimates
      for each son. Correlations between estimated and true breeding values ranged from
      0.60 to 0.79. Situations with unequally sized QTL effects and randomly dispersed
      QTL gave higher correlations. QTL positions could be estimated to within 2 cM or
      less.

PMID- 18076473
TI  - Accuracy of breeding values when using and ignoring the polygenic effect in
      genomic breeding value estimation with a marker density of one SNP per cM.
AB  - Genomic selection is based on breeding values that are estimated using genome
      wide dense marker maps. The objective of this paper was to investigate the effect
      of including or ignoring the polygenic effect on the accuracy of total genomic
      breeding values, when there is coverage of the genome with approximately one SNP
      per cM. The importance of the polygenic effect might differ for high and low
      heritability traits, and might depend on the design of the reference dataset.
      Hence, different scenarios were evaluated using stochastic simulation. Accuracies
      of the total breeding value of juvenile selection candidates depended on the
      number of animals included in the reference data. When excluding polygenic
      effects, those accuracies ranged from 0.38 to 0.55 and from 0.73 to 0.79 for
      traits with heritabilities of 10 and 50%, respectively. Accuracies were improved
      by including a polygenic effect in the model for the low heritability trait, when
      the LD-measure r2 between adjacent markers became smaller than approximately
      0.10, while for the high heritability trait there was already a small improvement
      at r2 between adjacent markers of 0.14. In all situations, the estimated total
      genetic variance was underestimated, particularly when the polygenic effect was
      excluded from the model. The haplotype variance was less underestimated when more
      animals were added in the reference dataset.

PMID- 18076474
TI  - Inbreeding in genome-wide selection.
AB  - Traditional selection methods, such as sib and best linear unbiased prediction
      (BLUP) selection, which increased genetic gain by increasing accuracy of
      evaluation have also led to an increased rate of inbreeding per generation
      (DeltaFG). This is not necessarily the case with genome-wide selection, which
      also increases genetic gain by increasing accuracy. This paper explains why
      genome-wide selection reduces DeltaFG when compared with sib and BLUP selection.
      Genome-wide selection achieves high accuracies of estimated breeding values
      through better prediction of the Mendelian sampling term component of breeding
      values. This increases differentiation between sibs and reduces coselection of
      sibs and DeltaFG. The high accuracy of genome-wide selection is expected to
      reduce the between family variance and reweigh the emphasis of estimated breeding
      values of individuals towards the Mendelian sampling term. Moreover, estimation
      induced intraclass correlations of sibs are expected to be lower in genome-wide
      selection leading to a further decrease of coselection of sibs when compared with
      BLUP. Genome-wide prediction of breeding values, therefore, enables increased
      genetic gain while at the same time reducing DeltaFG when compared with sib and
      BLUP selection.

PMID- 18076475
TI  - Machine learning classification procedure for selecting SNPs in genomic
      selection: application to early mortality in broilers.
AB  - Genome-wide association studies using single nucleotide polymorphisms (SNPs) can
      identify genetic variants related to complex traits. Typically thousands of SNPs
      are genotyped, whereas the number of phenotypes for which there is genomic
      information may be smaller. When predicting phenotypes, options for statistical
      model building range from incorporating all possible markers into the
      specification to including only sets of relevant SNPs (features). In the latter
      case, an efficient method of selecting influential features is required. A two
      step feature selection method for binary traits was developed, which consisted of
      filtering (using information gain), and wrapping (using naive Bayesian
      classification). The filter reduces the large number of SNPs to a much smaller
      size, to facilitate the wrapper step. As the procedure is tailored for discrete
      outcomes, an approach based on discretization of phenotypic values was developed,
      to enable feature selection in a classification framework. The method was applied
      to chick mortality rates (0-14 days of age) on progeny from 201 sires in a
      commercial broiler line, with the goal of identifying SNPs (over 5000) related to
      progeny mortality. To mimic a case-control study, sires were clustered into two
      groups, low and high, according to two arbitrarily chosen mortality rate cut
      points. By varying these thresholds, 11 different 'case-control' samples were
      formed, and the SNP selection procedure was applied to each sample. To compare
      the 11 sets of chosen SNPs, predicted residual sum of squares (PRESS) from a
      linear model was used. The two-step method improved naive Bayesian classification
      accuracy over the case without feature selection (from around 50 to above 90%
      without and with feature selection in each case-control sample). The best case
      control group (63 sires above or below the thresholds) had the smallest PRESS
      statistic among groups with model p-values below 0.003. The 17 SNPs selected
      using this group accounted for 31% of the variation in raw mortality rates
      between sire families.

PMID- 18076476
TI  - Noradrenaline and angiotensin II modify vascular prostanoid release in fructose
      fed hypertensive rats.
AB  - 1 A fructose-enriched diet induces hypertension, metabolic alterations and
      insulin resistance in rats, resembling human metabolic syndrome. Previously, we
      found that prostanoid production was altered in fructose-fed rats. 2 This study
      analysed the effects of incubation with noradrenaline (NA) and angiotensin II
      (Ang II) on prostanoid release in mesenteric vascular beds from control and
      fructose-fed rats. Animals which received fructose solution (10% w/v) for 22
      weeks showed higher systolic blood pressure and triglyceridaemia. 3 In controls,
      NA increased 6-keto-prostaglandin (PG) F(1)alpha (prostacyclin metabolite) and
      thromboxane (TX) production. Ang II increased only TX release. In fructose-fed
      animals, NA increased 6-keto-PG F(1)alpha and TX. PGF(2)alpha (vasoconstrictor)
      was also elevated. Ang II also increased PGF(2)alpha and PGE(2) levels. 4 In
      conclusion, in fructose rats Ang II in vitro stimulates a vasoconstrictor
      prostanoid not stimulated in controls. This could be related to the observed in
      vivo blood pressure increase. In fructose-fed animals, NA and Ang II also augment
      vasodilator prostanoids, suggesting a compensatory mechanism because of long-term
      hypertension.

PMID- 18076477
TI  - Haemodynamic changes after spinal cord transection are anaesthetic agent
      dependent.
AB  - 1 To evaluate the effect of high spinal cord transection (SCT), between T4 and
      T5, on the mean arterial pressure (MAP) and heart rate in animals anaesthetized
      with different anaesthetic agents: ether (n = 12), 20% urethane, 1.2 g kg(-1) (n
      = 12), 2% tri-bromide-ethanol, 200 mg kg(-1) (n = 12); chloral hydrate and
      urethane, 75 and 525 mg kg(-1) respectively (n = 12). 2 In the animals
      anaesthetized with ether or urethane, SCT caused an immediate major drop in MAP,
      with hypotension and bradycardia throughout the next 10 min. In the animals
      anaesthetized with urethane + chloralose or tri-bromide-ethanol, SCT transiently
      increased MAP with subsequent hypotension and bradycardia. 3 In summary, the
      haemodynamic changes after complete, high SCT are anaesthetic agent dependent.
      Further research about the exact mechanisms responsible for these diverse
      autonomic changes is warranted.

PMID- 18076478
TI  - Effects of sphingosine-1-phosphate and sphingosylphosphorylcholine on
      intracellular Ca2+ and cell death in prostate cancer cell lines.
AB  - The sphingolipid metabolites sphingosine-1-phosphate (S1P) and
      sphingosylphosphorylcholine (SPC) can be involved in cellular growth and
      apoptosis, by both receptor-dependent and -independent mechanisms. We
      investigated the role of S1P and SPC in intracellular Ca2+ elevation, cell
      proliferation and cell death in DU 145 and PC3 hormone-refractory prostate cancer
      cell lines. S1P and SPC increased intracellular Ca2+ levels, most likely in a
      receptor-independent manner. Surprisingly, both S1P and SPC did not stimulate but
      rather reduced cell growth through induction of apoptosis. Therefore, antagonists
      targeted against S1P, SPC and their receptors do not appear to be promising new
      approaches in the treatment of hormone-refractory prostate cancer.

PMID- 18076479
TI  - Effects of genistein and herbimycin, tyrosine kinase inhibitors, on catecholamine
      release in bovine adrenal chromaffin cells.
AB  - 1 The effects of genistein and herbimycin, tyrosine kinase inhibitors, on
      catecholamine (CA) release were examined in bovine adrenal chromaffin cells. 2 In
      intact cells, genistein (10-100 microm) and herbimycin (3-30 microm) inhibited CA
      release induced by acetylcholine (ACh; 100 microm) or the nicotinic receptor
      stimulant 1,1-dimethyl-4-phenyl-piperazinium (DMPP; 10 microm), but did not
      affect CA release induced by high K+ (40 mm). 3 Genistein and herbimycin
      inhibited (45)Ca2+ uptake induced by ACh (100 microm). 4 Neither genistein nor
      herbimycin affected [(3)H]nicotine binding with nicotinic receptors. 5 In beta
      escin-permeabilized cells, neither genistein nor herbimycin affected CA release
      induced by Ca2+ (1 microm). 6 These results suggest that protein tyrosine kinase
      plays the facilitatory role in the regulation of CA release induced by nicotinic
      receptor stimulation in stimulus-secretion coupling of bovine adrenal chromaffin
      cells.

PMID- 18076480
TI  - Regulatory false positives: true, false, or uncertain?
AB  - Hansen et al. (2007) recently assessed the historical performance of the
      precautionary principle in 88 specific cases, concluding that "applying our
      definition of a regulatory false positive, we were able to identify only four
      cases that fit the definition of a false positive." Empirically evaluating how
      prone the precautionary principle is to classify nonproblems as problems ("false
      positives") is an excellent idea. Yet, Hansen et al.'s implementation of this
      idea applies a diverse set of questionable criteria to label many highly
      uncertain risks as "real" even when no real or potential harm has actually been
      demonstrated. Examples include treating each of the following as reasons to
      categorize risks as "real": considering that a company's actions contaminated its
      own product; lack of a known exposure threshold for health effects; occurrence of
      a threat; treating deliberately conservative (upper-bound) regulatory assumptions
      as if they were true values; treating assumed exposures of children to
      contaminated soils (by ingestion) as evidence that feared dioxin risks are real;
      and treating claimed (sometimes ambiguous) epidemiological associations as if
      they were known to be true causal relations. Such criteria can classify even
      nonexistent and unknown risks as "real," providing an alternative possible
      explanation for why the authors failed to find more false positives, even if they
      exist.

PMID- 18076482
TI  - The future of BSE risk assessments. Introduction.

PMID- 18076483
TI  - Analyzing BSE transmission to quantify regional risk.
AB  - As a result of consumer fears and political concerns related to BSE as a risk to
      human health, a need has arisen recently for more sensitive methods to detect BSE
      and more accurate methods to determine BSE incidence. As a part of the
      development of such methods, it is important to be able to identify groups of
      animals with above-average BSE risk. One of the well-known risk factors for BSE
      is age, as very young animals do not develop the disease, and very old animals
      are less likely to develop the disease. Here, we analyze which factors have a
      strong influence on the age distribution of BSE in a population. Building on
      that, we develop a simple set of calculation rules for classifying the BSE risk
      in a given cattle population. Required inputs are data on imports and on the BSE
      control measures in place over the last 10 or 20 years.

PMID- 18076484
TI  - Quantitative risk assessment for bovine spongiform encephalopathy in low- or zero
      prevalence countries: the example of Norway.
AB  - A predictive case-cohort model is applied to Norwegian data to analyze the
      interaction between challenge and stability factors for bovine spongiform
      encephalopathy (BSE) during the period 1980-2010. For each year, the BSE risk in
      cattle is estimated as the expected number of cases. The age distribution of
      expected cases as well as the relative impact of different challenges is
      estimated. The model consists of a simple, transparent, and practical
      deterministic spreadsheet calculation model, in which the following country
      specific inputs are entered: (i) annual imports of live cattle and meat and bone
      meal, (ii) age distribution of native cattle, and (iii) estimated annual basic
      reproduction ratio (R(0)) for BSE. Results for Norway indicate that the highest
      risk of BSE cases was in 1989, when a total BSE risk of 0.13 cases per year was
      expected. After that date, the year-to-year decrease in risk ranged between 3%
      and 47%, except for a secondary peak in 1994 at 0.06 cases per year. The primary
      peak was almost entirely (99%) attributable to the importation of 11 cattle from
      the United Kingdom between 1982 and 1986. The secondary peak, in 1994, originated
      mainly from the recycling of the U.K. imported cattle (92%). In 2006, the
      remaining risk was 0.0003 cases per year, or 0.001 per million cows per year,
      with a maximal age-specific incidence of 0.03 cases per million per year in 10
      year-old cattle. Only 15% of the cases were expected in imported cattle. The
      probability of having zero cases in Norway in 2006 was estimated to be 99.97%.
      The model and results are compared to previous risk assessments of Norway by the
      EU.

PMID- 18076485
TI  - Identification of the characteristics and risk factors of the BSE epidemic in the
      Netherlands.
AB  - It is generally accepted that the bovine spongiform encephalopathy (BSE) epidemic
      is transmitted by feed contamination with meat and bone meal (MBM). Whether in
      some cases substances other than MBM have caused the spread of this disease
      cannot be excluded at present. Detailed knowledge about country-specific
      transmission routes and relevant risk factors is important to perform accurate
      risk analyses and to control BSE. In the present study all possible information
      of Dutch BSE cases was collected. The general epidemiological data were first
      used for a comprehensive descriptive analysis of the Dutch BSE epidemic. A case
      control study was performed to identify the risk factors associated with the
      occurrence of BSE cases in the Netherlands. Sixty-eight of the 76 BSE cases
      enrolled in the case-control study. With an oral questionnaire information was
      collected about cow and farm management. The same questionnaire was used in
      interviews at 128 randomly selected control farms. Detailed analysis of the case
      anamneses showed that all affected cows could have been exposed to MBM from pig
      or poultry feed as a result of cross-contamination. In the case-control study,
      only feed producer appeared to be a relevant risk factor. Differences in log odds
      between feed producers were related to the moment of separation of production
      lines and to the origin of the MBM. The results suggest that there were
      meaningful differences in the level of infectivity in MBM from different origins
      at the time that cross-contamination was still possible. No other risk factors,
      either farm or cow related, were significantly associated with the occurrence of
      BSE.

PMID- 18076486
TI  - BSE risk assessment as a basis for updating French screening policy.
AB  - The current French bovine spongiform encephalopathy (BSE) surveillance system,
      based on rapid testing of all cattle over 24 months of age and on clinical
      diagnosis, detects all clinical cases and some preclinical cases of BSE. Several
      indicators point to a marked shrinkage of the French BSE epidemic in recent
      years, owing to risk reduction measures. Meat and bone meal, the only known
      vector of the BSE agent, was banned in feed for all farmed species in November
      2000. Thus the surveillance system may be relaxed. The objective of this risk
      assessment study was to provide information for decisionmakers on the minimum age
      at which healthy and high-risk cattle now need to be screened with rapid tests.
      For this purpose, we used the back-calculation method to project the course of
      the BSE epidemic. We examined the predicted patterns of the number and age
      distribution of cases of BSE that would be detected by the different existing
      surveillance streams. Various theoretical sensitivities of rapid tests were
      explored. Assuming that feed-borne sources of infection no longer exist, and that
      BSE does not occur spontaneously, our models suggest that it would have been
      possible to raise the minimum age for rapid tests to 66 months in early 2006,
      whereas theoretical reasoning, based on the assumption that the total meat and
      bone meal ban was effective in November 2001, suggests that this age cutoff could
      only be raised to 48 months in early 2006. These results only apply to cattle
      born and bred in France. If the situation remains unchanged, the age cutoff could
      be raised incrementally each year.

PMID- 18076487
TI  - Complementary approach of data analysis and modeling to estimate the pattern of
      the BSE epidemic: the example of France.
AB  - Clinical surveillance was the only way to detect bovine spongiform encephalopathy
      (BSE) until July 2000 in France. From the 103 cases identified as such between
      1991 and June 2000, we used a back-calculation method to reconstruct the
      longitudinal trend of BSE infections. Between July 1987 and June 1997, an
      estimated 51,300 (CI =[24,300-84,700]) cattle were infected in France. The
      comprehensive surveillance of BSE with rapid tests, set up in France since 2001
      at the abattoir and fallen plant, allowed study of the relative exposure of the
      successive birth cohorts with nonconditional logistic regression models adjusted
      for possible confounding variables. The results were in agreement with those of
      the back-calculation model, estimating a decrease of the BSE exposure from the
      birth cohort July 1995-June 1996 that matched with the decrease of the infection
      after June 1996. In view of the long incubation period of BSE, it is not possible
      to precisely assess the impact of any control measure before several years.
      Modeling was therefore used to estimate prospectively the efficiency of the ban
      of meat and bone meal extended to all farm species in November 2000. Using
      parameters about age at infection and incubation time estimated earlier, we
      assessed the minimum time to first detection if infections still occurred. We
      have waited up to June 2007 to know if less than 100 infections occurred among
      French cattle during the 6 months following January 2001.

PMID- 18076488
TI  - Influence of routine slaughtering on the evolution of BSE: example of British and
      French slaughterings.
AB  - The aim of this article is to build a methodology allowing the study and the
      comparison of the potential spread of BSE at the scale of countries under
      different routine slaughtering conditions in order to evaluate the risk of
      nonextinction due to this slaughtering. We first model the evolution in discrete
      time of the proportion of animals in the latent period and that of infectives,
      assuming a very large branching population not necessarily constant in size, two
      age classes, less than 1-year-old animals, and adult animals. We analytically
      derive a bifurcation parameter rho(0) allowing us to predict either endemicity or
      extinction of the disease, which has the meaning of an epidemiological
      reproductive rate. We show that the classical reproductive number R(0) cannot be
      used for prediction if the size of the population, when healthy, does not remain
      stable throughout time. We illustrate the qualitative results by means of
      simulations with either the British routine slaughtering probabilities or the
      French ones, the other conditions being assumed identical in both countries. We
      show that the French probabilities lead to a higher risk of spread of the disease
      than the British ones, this result being mainly due to a smaller value of the
      routine slaughtering probability of the adult animals in France than in Great
      Britain.

PMID- 18076489
TI  - Comparison of the historic recycling risk for BSE in three European countries by
      calculating the basic reproduction ratio R0.
AB  - A deterministic model of BSE transmission is used to calculate the R(0) values
      for specific years of the BSE epidemics in the United Kingdom (UK), the
      Netherlands (NL), and Switzerland (CH). In all three countries, the R(0) values
      decreased below 1 after the introduction of a ban on feeding meat and bone meal
      (MBM) to ruminants around the 1990s. A variety of additional measures against BSE
      led to further decrease of R(0) to about 0.06 in the years around 1998. The
      calculated R(0) values were consistent with the observations made on the
      surveillance results for UK, but were partially conflicting with the surveillance
      results for NL and CH. There was evidence for a dependency of the BSE epidemic in
      NL and CH from an infection source not considered in the deterministic
      transmission model. Imports of MBM and feed components can be an explanation for
      this discrepancy, and the importance of imports for these observations is
      discussed.

PMID- 18076490
TI  - Exposure assessment of TSEs from the landspreading of meat and bone meal.
AB  - Recent changes in European legislation have meant that certain processed abattoir
      waste, which has been appropriately heat treated and ground to a specified
      particle size, can be spread on nonpasture agricultural land. This has opened the
      way for the potential landspreading of mammalian meat and bone meal (mMBM)
      derived from animals slaughtered for human consumption. This article reports on
      two separate case studies (Study 1 carried out in Great Britain (GB) and Study 2
      carried out in Ireland) on the potential exposure to TSE infectivity following
      the spreading of abattoir waste (derived from animals slaughtered for human
      consumption) on nonpasture agricultural land. For Study 1, the average TSE
      infectivity on nonpasture agricultural land per year from sheep with scrapie was
      found to be higher (five orders of magnitude) than that estimated for BSE in
      cattle (3.9 x 10(-3) Ovine Oral ID(50)/ton of soil compared to 3.3 x 10(-8)
      Bovine Oral ID(50)/ton of soil). The mean estimate for BSE in sheep was 8.1 x 10(
      6) Ovine Oral ID(50)/ton of soil. The mean level of infectivity in mMBM was
      assessed to be 1.2 x 10(-5) and 2.36 x 10(-5) ID(50)/ton of mMBM for Study 1 and
      2, respectively. For Study 2 the spreading of mMBM was estimated to result in
      infectivity on nonpasture land of 1.62 x 10(-8) Bovine Oral ID(50)/m(3). The mean
      simulated probability of infection per year per bovine animal was 1.11 x 10(-9).
      Given the low infectivity density and corresponding low risks to bovines the
      spreading of mMBM could be considered a viable alternative for the utilization of
      mMBM.

PMID- 18076491
TI  - Assessment of inhalation exposures and potential health risks to the general
      population that resulted from the collapse of the World Trade Center towers.
AB  - In the days following the collapse of the World Trade Center (WTC) towers on
      September 11, 2001 (9/11), the U.S. Environmental Protection Agency (EPA)
      initiated numerous air monitoring activities to better understand the ongoing
      impact of emissions from that disaster. Using these data, EPA conducted an
      inhalation exposure and human health risk assessment to the general population.
      This assessment does not address exposures and potential impacts that could have
      occurred to rescue workers, firefighters, and other site workers, nor does it
      address exposures that could have occurred in the indoor environment.
      Contaminants evaluated include particulate matter (PM), metals, polychlorinated
      biphenyls, dioxins, asbestos, volatile organic compounds, particle-bound
      polycyclic aromatic hydrocarbons, silica, and synthetic vitreous fibers (SVFs).
      This evaluation yielded three principal findings. (1) Persons exposed to
      extremely high levels of ambient PM and its components, SVFs, and other
      contaminants during the collapse of the WTC towers, and for several hours
      afterward, were likely to be at risk for acute and potentially chronic
      respiratory effects. (2) Available data suggest that contaminant concentrations
      within and near ground zero (GZ) remained significantly elevated above background
      levels for a few days after 9/11. Because only limited data on these critical few
      days were available, exposures and potential health impacts could not be
      evaluated with certainty for this time period. (3) Except for inhalation
      exposures that may have occurred on 9/11 and a few days afterward, the ambient
      air concentration data suggest that persons in the general population were
      unlikely to suffer short-term or long-term adverse health effects caused by
      inhalation exposures. While this analysis by EPA evaluated the potential for
      health impacts based on measured air concentrations, epidemiological studies
      conducted by organizations other than EPA have attempted to identify actual
      impacts. Such studies have identified respiratory effects in worker and general
      populations, and developmental effects in newborns whose mothers were near GZ on
      9/11 or shortly thereafter. While researchers are not able to identify specific
      times and even exactly which contaminants are the cause of these effects, they
      have nonetheless concluded that exposure to WTC contaminants (and/or maternal
      stress, in the case of developmental effects) resulted in these effects, and have
      identified the time period including 9/11 itself and the days and few weeks
      afterward as a period of most concern based on high concentrations of key
      pollutants in the air and dust.

PMID- 18076492
TI  - Development of a screening approach to interpret human biomonitoring data on
      volatile organic compounds: reverse dosimetry on biomonitoring data for
      trichloroethylene.
AB  - A screening approach is developed for volatile organic compounds (VOCs) to
      estimate exposures that correspond to levels measured in fluids and/or tissues in
      human biomonitoring studies. The approach makes use of a generic physiologically
      based pharmacokinetic (PBPK) model coupled with exposure pattern
      characterization, Monte Carlo analysis, and quantitative structure property
      relationships (QSPRs). QSPRs are used for VOCs with minimal data to develop
      chemical-specific parameters needed for the PBPK model. The PBPK model is capable
      of simulating VOC kinetics following multiple routes of exposure, such as oral
      exposure via water ingestion and inhalation exposure during shower events. Using
      published human biomonitoring data of trichloroethylene (TCE), the generic model
      is evaluated to determine how well it estimates TCE concentrations in blood based
      on the known drinking water concentrations. In addition, Monte Carlo analysis is
      conducted to characterize the impact of the following factors: (1) uncertainties
      in the QSPR-estimated chemical-specific parameters; (2) variability in
      physiological parameters; and (3) variability in exposure patterns. The results
      indicate that uncertainty in chemical-specific parameters makes only a minor
      contribution to the overall variability and uncertainty in the predicted TCE
      concentrations in blood. The model is used in a reverse dosimetry approach to
      derive estimates of TCE concentrations in drinking water based on given
      measurements of TCE in blood, for comparison to the U.S. EPA's Maximum
      Contaminant Level in drinking water. This example demonstrates how a reverse
      dosimetry approach can be used to facilitate interpretation of human
      biomonitoring data in a health risk context by deriving external exposures that
      are consistent with a biomonitoring data set, thereby permitting comparison with
      health-based exposure guidelines.

PMID- 18076493
TI  - Uncertainties in the CIIT model for formaldehyde-induced carcinogenicity in the
      rat: a limited sensitivity analysis-I.
AB  - Scientists at the CIIT Centers for Health Research (Conolly et al., 2000, 2003;
      Kimbell et al., 2001a, 2001b) developed a two-stage clonal expansion model of
      formaldehyde-induced nasal cancers in the F344 rat that made extensive use of
      mechanistic information. An inference of their modeling approach was that
      formaldehyde-induced tumorigenicity could be optimally explained without the role
      of formaldehyde's mutagenic action. In this article, we examine the strength of
      this result and modify select features to examine the sensitivity of the
      predicted dose response to select assumptions. We implement solutions to the two
      stage cancer model that are valid for nonhomogeneous models (i.e., models with
      time-dependent parameters), thus accounting for time dependence in variables. In
      this reimplementation, we examine the sensitivity of model predictions to pooling
      historical and concurrent control data, and to lumping sacrificed animals in
      which tumors were discovered incidentally with those in which death was caused by
      the tumors. We found the CIIT model results were not significantly altered with
      the nonhomogeneous solutions. Dose-response predictions below the range of
      exposures where tumors occurred in the bioassays were highly sensitive to the
      choice of control data. In the range of exposures where tumors were observed, the
      model attributed up to 74% of the added tumor probability to formaldehyde's
      mutagenic action when our reanalysis restricted the use of the National
      Toxicology Program (NTP) historical control data to only those obtained from
      inhalation exposures. Model results were insensitive to hourly or daily temporal
      variations in DNA protein cross-link (DPX) concentration, a surrogate for the
      dose-metric linked to formaldehyde-induced mutations, prompting us to utilize
      weekly averages for this quantity. Various other biological and mathematical
      uncertainties in the model have been retained unmodified in this analysis. These
      include model specification of initiated cell division and death rates, and
      uncertainty and variability in the dose response for cell replication rates,
      issues that will be considered in a future paper.

PMID- 18076494
TI  - Predicting severity of foreign body injuries in children in upper airways: an
      approach based on regression trees.
AB  - The entry of a small item into the upper airways is one of the leading causes of
      injuries in children up to 14 years old. The aim of this study is to characterize
      types of objects causing choking along with the features of the children involved
      in the accident and compare results with current standards. The European Survey
      on Foreign Bodies Injuries Study (ESFBI) collected data on foreign body injuries
      from 19 European countries. The data from ESFBI were selected according to the
      ICD-9-CM codes 933 (foreign body in the pharynx and larynx) and 934 (foreign body
      in the trachea, bronchi, and lungs). Both a classification tree and a linear
      discriminant analysis (LDA) have been set up to predict the probability that an
      injured child experiences a hospitalization. The classification tree provides
      flowchart-type decision rules and allows for analyzing the impact of the item
      features, the children characteristics, and the circumstances of the accidents on
      the severity of the foreign body injuries. Results showed that children younger
      than 3.5 who are involved in an accident have a high probability to experience a
      hospitalization.

PMID- 18076495
TI  - Risk analysis for critical asset protection.
AB  - This article proposes a quantitative risk assessment and management framework
      that supports strategic asset-level resource allocation decision making for
      critical infrastructure and key resource protection. The proposed framework
      consists of five phases: scenario identification, consequence and criticality
      assessment, security vulnerability assessment, threat likelihood assessment, and
      benefit-cost analysis. Key innovations in this methodology include its initial
      focus on fundamental asset characteristics to generate an exhaustive set of
      plausible threat scenarios based on a target susceptibility matrix (which we
      refer to as asset-driven analysis) and an approach to threat likelihood
      assessment that captures adversary tendencies to shift their preferences in
      response to security investments based on the expected utilities of alternative
      attack profiles assessed from the adversary perspective. A notional example is
      provided to demonstrate an application of the proposed framework. Extensions of
      this model to support strategic portfolio-level analysis and tactical risk
      analysis are suggested.

PMID- 18076496
TI  - A framework for linking cybersecurity metrics to the modeling of macroeconomic
      interdependencies.
AB  - Hierarchical decision making is a multidimensional process involving management
      of multiple objectives (with associated metrics and tradeoffs in terms of costs,
      benefits, and risks), which span various levels of a large-scale system. The
      nation is a hierarchical system as it consists multiple classes of decisionmakers
      and stakeholders ranging from national policymakers to operators of specific
      critical infrastructure subsystems. Critical infrastructures (e.g.,
      transportation, telecommunications, power, banking, etc.) are highly complex and
      interconnected. These interconnections take the form of flows of information,
      shared security, and physical flows of commodities, among others. In recent
      years, economic and infrastructure sectors have become increasingly dependent on
      networked information systems for efficient operations and timely delivery of
      products and services. In order to ensure the stability, sustainability, and
      operability of our critical economic and infrastructure sectors, it is imperative
      to understand their inherent physical and economic linkages, in addition to their
      cyber interdependencies. An interdependency model based on a transformation of
      the Leontief input-output (I-O) model can be used for modeling: (1) the steady
      state economic effects triggered by a consumption shift in a given sector (or set
      of sectors); and (2) the resulting ripple effects to other sectors. The
      inoperability metric is calculated for each sector; this is achieved by
      converting the economic impact (typically in monetary units) into a percentage
      value relative to the size of the sector. Disruptive events such as terrorist
      attacks, natural disasters, and large-scale accidents have historically shown
      cascading effects on both consumption and production. Hence, a dynamic model
      extension is necessary to demonstrate the interplay between combined demand and
      supply effects. The result is a foundational framework for modeling cybersecurity
      scenarios for the oil and gas sector. A hypothetical case study examines a cyber
      attack that causes a 5-week shortfall in the crude oil supply in the Gulf Coast
      area.

PMID- 18076497
TI  - On determining specifications and selections of alternative technologies for
      airport checked-baggage security screening.
AB  - Federal law mandates that every checked bag at all commercial airports be
      screened by explosive detection systems (EDS), explosive trace detection systems
      (ETD), or alternative technologies. These technologies serve as critical
      components of airport security systems that strive to reduce security risks at
      both national and global levels. To improve the operational efficiency and
      airport security, emerging image-based technologies have been developed, such as
      dual-energy X-ray (DX), backscatter X-ray (BX), and multiview tomography (MVT).
      These technologies differ widely in purchasing cost, maintenance cost, operating
      cost, processing rate, and accuracy. Based on a mathematical framework that takes
      into account all these factors, this article investigates two critical issues for
      operating screening devices: setting specifications for continuous security
      responses by different technologies; and selecting technology or combination of
      technologies for efficient 100% baggage screening. For continuous security
      responses, specifications or thresholds are used for classifying threat items
      from nonthreat items. By investigating the setting of specifications on system
      security responses, this article assesses the risk and cost effectiveness of
      various technologies for both single-device and two-device systems. The findings
      provide the best selection of image-based technologies for both single-device and
      two-device systems. Our study suggests that two-device systems outperform single
      device systems in terms of both cost effectiveness and accuracy. The model can be
      readily extended to evaluate risk and cost effectiveness of multiple-device
      systems for airport checked-baggage security screening.

PMID- 18076498
TI  - Life cycle risks for human health: a comparison of petroleum versus bio-based
      production of five bulk organic chemicals.
AB  - This article describes the development and application of a generic approach to
      the comparative assessment of risks related to the production of organic
      chemicals by petrochemical processes versus white biotechnology. White
      biotechnology, also referred to as industrial biotechnology, typically uses bio
      based feedstocks instead of the fossil raw materials used in the petrochemical
      sector. The purpose of this study was to investigate whether the production of
      chemicals by means of white biotechnology has lower conventional risks than their
      production by petrochemical processes. Conventional risks are the risks of well
      established processes, and not those related to genetically modified
      microorganisms and plants. Our approach combines classical risk assessment
      methods (largely based on toxicology), as developed by the life cycle assessment
      (LCA) community, with statistics on technological disasters, accidents, and work
      related illnesses. Moreover, it covers the total process chain for both
      petrochemical and bio-based products from cradle to grave. The approach was
      applied to five products: the plastics polytrimethylene terephthalate (PTT),
      polyhydroxyalkanoates (PHA), polyethylene terephthalate (PET), polyethylene (PE),
      and ethanol. Our results show that the conventional risks related to the white
      biotechnology products studied are lower than those of the petrochemical
      products. However, considering the uncertainties with respect to the ranges of
      input data, the (incomplete) coverage of emissions by the environmental priority
      strategies (EPS) 2000 method, and the uncertainties of the assumptions made in
      this study (i.e., large to very large), the differences in results between bio
      based and petrochemical products fall into the uncertainty range. Because of
      this, future research is necessary to decrease the uncertainties before we can
      conclude that the conventional risks of biotechnologically produced chemicals are
      lower than those of fossil-fuel-derived chemicals.

PMID- 18076499
TI  - Probabilistic reliability modeling for oil exploration & production (E&P)
      facilities in the tallgrass prairie preserve.
AB  - The aging domestic oil production infrastructure represents a high risk to the
      environment because of the type of fluids being handled (oil and brine) and the
      potential for accidental release of these fluids into sensitive ecosystems.
      Currently, there is not a quantitative risk model directly applicable to onshore
      oil exploration and production (E&P) facilities. We report on a probabilistic
      reliability model created for onshore exploration and production (E&P)
      facilities. Reliability theory, failure modes and effects analysis (FMEA), and
      event trees were used to develop the model estimates of the failure probability
      of typical oil production equipment. Monte Carlo simulation was used to translate
      uncertainty in input parameter values to uncertainty in the model output. The
      predicted failure rates were calibrated to available failure rate information by
      adjusting probability density function parameters used as random variates in the
      Monte Carlo simulations. The mean and standard deviation of normal variate
      distributions from which the Weibull distribution characteristic life was chosen
      were used as adjustable parameters in the model calibration. The model was
      applied to oil production leases in the Tallgrass Prairie Preserve, Oklahoma. We
      present the estimated failure probability due to the combination of the most
      significant failure modes associated with each type of equipment (pumps, tanks,
      and pipes). The results show that the estimated probability of failure for tanks
      is about the same as that for pipes, but that pumps have much lower failure
      probability. The model can provide necessary equipment reliability information
      for proactive risk management at the lease level by providing quantitative
      information to base allocation of maintenance resources to high-risk equipment
      that will minimize both lost production and ecosystem damage.

PMID- 18076500
TI  - Reducing the risk of human extinction.
AB  - In this century a number of events could extinguish humanity. The probability of
      these events may be very low, but the expected value of preventing them could be
      high, as it represents the value of all future human lives. We review the
      challenges to studying human extinction risks and, by way of example, estimate
      the cost effectiveness of preventing extinction-level asteroid impacts.

PMID- 18076501
TI  - Systemic valuation of strategic preparedness through application of the
      inoperability input-output model with lessons learned from Hurricane Katrina.
AB  - The U.S. Department of Homeland Security (DHS) has mandated all regions to
      "carefully weigh the benefit of each homeland security endeavor and only allocate
      resources where the benefit of reducing risk is worth the amount of additional
      cost" (DHS, 2006, p. 64). This mandate illuminates the need to develop methods
      for systemic valuation of preparedness measures that support strategic decision
      making. This article proposes an analysis method that naturally emerges from the
      structure of the inoperability input-output model (IIM) through which various
      regional- and sector-specific impact analyses can be cost-effectively integrated
      for natural and man-made disasters. The IIM is described extensively in a
      companion paper (Lian et al., 2007). Its reliance on data classifications
      structured by the U.S. Census Bureau and its extensive accounting of economic
      interdependencies enables us to decompose a risk analysis activity, perform
      independent assessments, and properly integrate the assessment for a systemic
      valuation of risk and risk management activity. In this article, we account for
      and assess some of the major impacts of Hurricanes Katrina and Rita to
      demonstrate this use of the IIM and illustrate hypothetical, reduced impacts
      resulting from various strategic preparedness decisions. Our results indicate the
      capability of the IIM to guide the decision-making processes involved in
      developing a preparedness strategy.

PMID- 18076502
TI  - The roles of group membership, beliefs, and norms in ecological risk perception.
AB  - Variability in ecological risk perceptions was investigated by surveying members
      of four stakeholder groups commonly involved in environmental policy debates.
      Fifty-six individuals from government, industry, environmental, and general
      public groups completed a risk-perception survey in which they evaluated 34
      environmental hazards on 17 attributes and also evaluated the riskiness and
      acceptability of each hazard. In addition, participants reported their
      environmental beliefs and norms using Dunlap et al.'s revised New Ecological
      Paradigm Scale and modified versions of Schwartz's Awareness of Consequences and
      Personal Norms Scales. Group membership was predictive of participants' scores on
      the belief and norm scales. Factor analysis of attribute ratings (averaged across
      participants) revealed the anticipated three oblique factors: ecological impacts,
      scientific understanding, and aesthetic impacts. Factor patterns were very
      similar for the four stakeholder groups. Factors from the aggregate analysis were
      predictive of individuals' riskiness judgments, but these relationships were
      moderated by participants' group membership, beliefs, and norms. Compared to
      members of other groups, members of the general public placed less emphasis on
      ecological impacts and more emphasis on the other two factors when judging the
      ecological riskiness of hazards. To our knowledge, these results represent the
      first formal tests of interactions between hazard characteristics and participant
      characteristics in determining riskiness judgments, and illustrate how
      traditional psychometric analyses can be successfully coupled with individual
      difference measures to improve the understanding of risk perception.

PMID- 18076503
TI  - Water quality failures in distribution networks-risk analysis using fuzzy logic
      and evidential reasoning.
AB  - The evaluation of the risk of water quality failures in a distribution network is
      a challenging task given that much of the available data are highly uncertain and
      vague, and many of the mechanisms are not fully understood. Consequently, a
      systematic approach is required to handle quantitative-qualitative data as well
      as a means to update existing information when new knowledge and data become
      available. Five general pathways (mechanisms) through which a water quality
      failure can occur in the distribution network are identified in this article.
      These include contaminant intrusion, leaching and corrosion, biofilm formation
      and microbial regrowth, permeation, and water treatment breakthrough (including
      disinfection byproducts formation). The proposed methodology is demonstrated
      using a simplified example for water quality failures in a distribution network.
      This article builds upon the previous developments of aggregative risk analysis
      approach. Each basic risk item in a hierarchical framework is expressed by a
      triangular fuzzy number, which is derived from the composition of the likelihood
      of a failure event and the associated failure consequence. An analytic hierarchy
      process is used to estimate weights required for grouping noncommensurate risk
      sources. The evidential reasoning is proposed to incorporate newly arrived data
      for the updating of existing risk estimates. The exponential ordered weighted
      averaging operators are used for defuzzification to incorporate attitudinal
      dimension for risk management. It is envisaged that the proposed approach could
      serve as a basis to benchmark acceptable risks in water distribution networks.

PMID- 18076504
TI  - Global health law, ethics, and policy.

PMID- 18076505
TI  - The duty of States to assist other States in need: ethics, human rights, and
      international law.
AB  - In this article, Gostin and Archer explore the varied lenses through which
      governments are obligated to address humanitarian needs. States'responsibilities
      to help others derive from domestic law, political commitments, ethical values,
      national interests, and international law. What is needed, however, is clarity
      and detailed standards so that States can operationalize this responsibility,
      making it real for developing countries. Transnational cooperation needs to be
      more effective and consistent to provide assistance for the world's poorest and
      least healthy people.

PMID- 18076506
TI  - The proliferation of human rights in global health governance.
AB  - Human rights play an integral role in the global governance of health. Recently,
      both structural and normative aspects of human rights have proliferated across
      multiple levels and within multiple contexts around the world. Human rights
      proliferation is likely to have a positive impact on the governance of health
      because it can expand the avenues through which a human rights framework or human
      rights norms may be used to address and improve health.

PMID- 18076507
TI  - Advancing health rights in a globalized world: responding to globalization
      through a collective human right to public health.
AB  - The right to health was codified in Article 12 of the International Covenant on
      Economic, Social and Cultural Rights as an individual right, focusing on
      individual health services at the expense of public health systems. This article
      assesses the ways in which the individual human right to health has evolved to
      meet collective threats to the public's health. Despite its repeated expansions,
      the individual right to health remains normatively incapable of addressing the
      injurious societal ramifcations of economic globalization, advancing individual
      rights to alleviate collective inequalities in underlying determinants of health.
      By examining modern changes to underlying determinants of health, this article
      concludes that responding to globalized health threats necessitates a collective
      right to public health.

PMID- 18076508
TI  - Addressing the global tragedy of needless pain: rethinking the United Nations
      single convention on narcotic drugs.
AB  - The lack of medical availability of effective pain medication is an enduring and
      expanding global health calamity. Despite important medical advances, pain
      remains severely under-treated worldwide, particularly in developing countries.
      This article contributes to the discussion of this global health crisis by
      considering international legal and institutional mechanisms to promote wider
      accessibility to critical narcotic drugs for pain relief.

PMID- 18076509
TI  - Mapping the scope and opportunities for public health law in liberal democracies.
AB  - The two questions, "What is public health law?" and "How can law improve the
      public's health?" are perennial ones for public health law scholars. This paper
      proposes a framework for conceptualizing discussion and debate about the scope
      and opportunities for public health law within liberal democracies. Part 2 of the
      paper draws selectively on this framework in order to highlight some areas where
      law's potential role deserves greater acknowledgment and exploration.

PMID- 18076510
TI  - An exploration of conceptual and temporal fallacies in international health law
      and promotion of global public health preparedness.
AB  - In February 2007, Indonesia withheld sharing H5N1 viral samples in order to
      compel the World Health Organization and Member States to guarantee future access
      to vaccines for States disproportionately burdened by infectious diseases. This
      article explores conceptual and temporal fallacies in the International Health
      Regulations (2005) and the Doha Declaration on the TRIPS Agreement and Public
      Health, as relates to global public health preparedness. Recommendations include
      adopting laws to facilitate non-pharmaceutical interventions; securing the rights
      of affected populations; and fostering inter-State collaborations to promote
      intra-State public health capacity building.

PMID- 18076511
TI  - Limited liability and the public's health.
AB  - Corporations, through their products and behaviors, exert a strong effect on the
      well-being of populations. Industries including firearms, motor vehicles,
      tobacco, and alcohol produce and market products negatively impact public health.
      All of these industries are composed of corporations, which are legal fictions
      designed to provide limited exposure to liability, through a variety of
      mechanisms, for their investors and directors. This means that when actions are
      taken on behalf of a corporate entity, the individuals responsible generally will
      not face personal liability for the negative results of those actions. To
      illustrate this point, this article considers corporate products or practices
      that have caused harm in varied settings, and analyzes the role that limited
      liability played in these cases. In addition, the article identifies ways to
      modify or eliminate some of the principles and practices that accompany limited
      liability.

PMID- 18076512
TI  - Detention and the evolving threat of tuberculosis: evidence, ethics, and law.
AB  - The issue of detention as a public health control measure has attracted attention
      recently. This is because the threat of strains of tuberculosis that are
      resistant to a wider range of drugs has been identified, and there is renewed
      concern that public health is threatened. This paper considers whether
      involuntary detention is justified where voluntary measures have failed or where
      a patient poses a danger, albeit uncertain, to the public. We discuss the need
      for strengthening evidence-based assessments of public health risk and suggest
      that we should reflect more profoundly on the philosophical foundations upon
      which our policies and practices are grounded.

PMID- 18076513
TI  - Through the quarantine looking glass: drug-resistant tuberculosis and public
      health governance, law, and ethics.
AB  - The incident in May-June 2007 involving a U.S. citizen traveling internationally
      while infected with drug-resistant tuberculosis involved the U.S. federal
      government's application of its quarantine and isolation powers. The incident and
      the isolation order raised numerous important issues for public health
      governance, law, and ethics. This article explores many of these issues by
      examining how the exercise of quarantine powers provides a powerful lens through
      which to understand how societies respond to and attempt to govern threats posed
      by dangerous, contagious pathogens. The article considers historical aspects of
      governmental power to quarantine and isolate individuals and groups; analyzes the
      current state of quarantine and isolation law in the United States in light of
      the recent incident with drug-resistant tuberculosis; and explores global aspects
      of public health governance and law highlighted by this incident.

PMID- 18076514
TI  - Nanotechnology in global medicine and human biosecurity: private interests,
      policy dilemmas, and the calibration of public health law.
AB  - This paper considers how best to approach dilemmas posed to global health and
      biosecurity policy by increasing advances in practical applications of
      nanotechnology. The type of nano-technology policy dilemmas discussed include:
      (1) expenditure of public funds, (2) public-funded research priorities, (3)
      public confidence in government and science and, finally, (4) public safety. The
      article examines the value in this context of a legal obligation that the
      development of relevant public health law be calibrated against less corporate
      influenced norms issuing from bioethics and international human rights.

PMID- 18076515
TI  - What is fair? Choice, fairness, and transparency in access to prescription
      medicines in the United States and Australia.
AB  - The importance of prescription drugs to modern medical practice, coupled with
      their increasing costs, has strengthened imperatives for national health policies
      that ensure safety and quality, facilitate affordable access, and promote
      rational use. Australia has made universal and affordable prescription drug
      coverage a priority for decades, within a policy framework that emphasizes equity
      and increasing transparency in coverage design and payment decisions. By
      contrast, the U.S. lacks such a national policy. Furthermore, federal Medicare
      reforms aimed at making appropriate drug coverage affordable and accessible
      employs two icons of the U.S. perception of fairness--the right to choose and the
      right to challenge coverage design limits--that mask the limited nature of the
      assistance. As the U.S. seeks to impose its values and priorities on other
      nations through the negotiation of bilateral and regional trade agreements, it
      becomes important to consider the two national experiences, in order to avoid
      trading illusory notions of fairness for true population equity.

PMID- 18076516
TI  - Looking ahead: addressing ethical challenges in public health practice.
AB  - Ethical challenges in public health can have a significant impact on the health
      of communities if they impede efficiencies and best practices. Competing needs
      for resources and a plurality of values can challenge public health policymakers
      and practitioners to make fair and effective decisions for their communities. In
      this paper, the authors offer an analytic framework designed to assist
      policymakers and practitioners in managing the ethical tensions they face in
      daily practice. Their framework is built upon the following set of six
      considerations: determining population-level utility of the proposed action;
      demonstrating evidence of need and effectiveness of actions; establishing
      fairness of goals and proposed implementation strategies; ensuring
      accountability; and, assessing expected efficiencies and costs associated with
      the proposed action. Together, these considerations create a structured guide to
      assist decision-makers in identifying potential ethical challenges and in
      assessing the moral considerations that underlie public health practice - and
      possibly even, if the conditions are met, reduce the creation of ethical tension.
      Although the authors'empirical experiences provide the basis for the framework
      advanced here, their approach remains to be tested and evaluated by public health
      practitioners.

PMID- 18076517
TI  - The ethics of restrictive licensing for handguns: comparing the United States and
      Canadian approaches to handgun regulation.
AB  - The United States and Canada regulate firearms, particularly handguns, quite
      differently. With only a few state and local exceptions, the U.S. approach
      emphasizes the ability of most individuals to purchase, possess, and carry
      handguns. By comparison, Canada has a form of restrictive licensing for handguns
      that places a premium on community safety. The authors first review the potential
      individual and community level harms and benefits associated with these differing
      fre-arm policies. Using this information, they explore the ethical dimensions of
      the U.S. and Canadian approaches through three major themes of autonomy,
      prevention of harms, and social justice. The authors conclude that the Canadian
      approach is consistent with respect for the autonomy of persons, fosters the
      prevention of harms, and more appropriately furthers social justice.

PMID- 18076518
TI  - The ancillary-care responsibilities of researchers: reasonable but not great
      expectations.
AB  - This paper argues that, in a community of rights, the prima facie
      responsibilities of researchers to attend to the ancillary-care needs of their
      participants would be determined by a four-stage test (relating to placement,
      capacity, reasonable imposition, and fair demand). This test, it is suggested,
      sets a standard (and an example) for common law courts that are invited to
      recognize the ancillary-care responsibilities of researchers, whether as a matter
      of contract or tort law.

PMID- 18076519
TI  - Ethical implications of physician involvement in lawsuits on behalf of the
      tobacco industry.
AB  - The statements of physicians who serve as expert witnesses for the tobacco
      industry reveal subtle but significant problems. Some expert testimony obfuscates
      the important issues, and some initially reasonable statements later evolve into
      extreme positions during cross-examination. Such statements fall into a "gray
      area" of professional ethics, potentially misleading juries and adversely
      affecting professional integrity. Medical associations can and should strongly
      enforce professional standards that do not tolerate tobacco industry influence on
      physician expert witnesses.

PMID- 18076520
TI  - Jewish perspectives on the use of preimplantation genetic diagnosis.
AB  - This article presents an analysis of the ethical considerations raised by
      preimplantation genetic diagnosis (PGD) from a Jewish perspective. It weighs the
      Jewish imperatives to pursue good health against a number of harms that may
      follow from the expanded use of PGD technology, including increased medical risk
      to the mother, the destruction of embryos and possible emotional harm to the
      child born from this procedure. It pays special attention to the potential harms
      that may befall those in society who do not have access to PGD or who choose not
      to employ it.

PMID- 18076521
TI  - Luck, genes, and equality.
AB  - This essay considers principles of distributive justice for access to
      reproductive biotechnologies which make it possible to enhance the traits of
      human offspring. The author provides prima facie reason to think that
      redistributive principles apply to genetic goods and proceed to evaluate the way
      in which four distributive patterns--egalitarianism, luck egalitarianism,
      prioritarianism, and suffcientarianism--would implement a just distribution of
      genetic goods. He argues that the currency of genetic redistribution consists in
      natural primary goods like health, vision, and rationality as these goods
      contribute to the biological component of basic capabilities, like being healthy,
      seeing properly, and being able to reason. The author develops a mixed
      sufficiency/priority approach to genetic enhancement, and defends this approach
      against objections.

PMID- 18076522
TI  - Ethics at phase 0: clarifying the issues.
AB  - The Food and Drug Administration (FDA) and the European Agency for the Evaluation
      of Medicinal Products (EMEA) recently issued documents encouraging sponsors to
      consider microdose testing before launching Phase I trials, and many commentators
      predict that such methodologies will be applied more routinely in drug
      development. However, exploratory testing has provoked several ethical
      criticisms. Skeptics question the value and validity of microdose trials, and
      whether they present a reasonable balance of risks and benefits for subjects.
      Another major criticism is that such studies serve mainly commercial ends. The
      present article explores these and other ethical concerns for studies conducted
      in the oncology setting. It concludes that microdosing is not inconsistent with
      prevailing practices in Phase I research, and that in principle, such studies
      could strengthen the ethical basis for Phase I trials by providing them better
      evidentiary justification.

PMID- 18076523
TI  - Currents in contemporary ethics. The tuberculosis scare in retrospect.

PMID- 18076524
TI  - Teaching health law. How well do we engage our students?

PMID- 18076525
TI  - The ethical health lawyer. The ethical health lawyer in the legislature.

PMID- 18076527
TI  - State attempts to expand abortion informed consent requirements: new life after
      Gonzales v. Carhart?

PMID- 18076528
TI  - Magnitude of effect of lithium in short-term efficacy studies of moderate to
      severe manic episode.
AB  - OBJECTIVES: To provide an accurate estimation of the magnitude of effect of
      lithium in short-term efficacy studies conducted in patients with moderate to
      severe manic episode. METHODS: All placebo-controlled randomized studies
      submitted to the Medicines Evaluation Board (MEB) in which lithium was used as
      the third study arm were selected for the meta-analysis. The studies were part of
      registration files submitted to the MEB between the years 1997 and 2005. In
      addition, Medline and EMbase searches were conducted with the key words 'manic'
      ('mania' for the EMbase search) and 'placebo' in order to identify additional
      placebo-controlled studies of lithium. This search was updated until March 1,
      2006. Two effect size indicators were used based on the primary outcome measure
      of each study: Cohen's standardized effect size based on the difference in mean
      change from baseline, and numbers needed to treat (NNT) based on the difference
      in treatment response defined as >or=50% improvement from baseline on day 21.
      RESULTS: Six studies were identified. They involved a combined total of 470
      patients in the lithium groups and 562 in the placebo groups. The overall
      standardized effect size was 0.40 [95% confidence interval (CI): 0.28, 0.53] and
      the overall NNT for response was 6 (95% CI: 4, 13). In the placebo groups
      response rates varied from 21% to 47%. CONCLUSIONS: The results indicate that
      lithium is an effective drug in the treatment of moderate to severe manic
      episode. The variability in placebo response indicates that a placebo control arm
      in efficacy studies among patients with moderate to severe manic episode is
      necessary.

PMID- 18076529
TI  - White matter abnormalities in children with and at risk for bipolar disorder.
AB  - OBJECTIVES: Diffusion tensor magnetic resonance imaging (DT-MRI) assesses the
      integrity of white matter (WM) tracts in the brain. Children with bipolar
      disorder (BPD) may have WM abnormalities that precede illness onset. To more
      fully examine this possibility, we scanned children with DSM-IV BPD and compared
      them to healthy peers and children at risk for BPD (AR-BPD), defined as having a
      first-degree relative with the disorder. METHODS: Ten children with BPD, eight
      healthy controls (HC), and seven AR-BPD, similar in age, had MRI scans on a 1.5
      Tesla GE scanner, including a standard DT-MRI sequence (T2-EPI) with 25 axial
      slices. Fractional anisotropy (FA) values were compared between groups to
      determine regions of significant difference (p < 0.05). RESULTS: Compared to HC,
      children with BPD had decreased FA in right and left superior frontal tracts,
      including the superior longitudinal fasciculus I (SLF I) and the cingulate
      paracingulate WM (CG-PAC(WM)). In addition, the BPD group had reduced FA in left
      orbital frontal WM and the right corpus callosum body. Compared to AR-BPD,
      children with BPD showed reduced FA in the right and left CG-PAC(WM). Both the
      BPD and AR-BPD groups showed reduced FA relative to HC in bilateral SLF I.
      CONCLUSIONS: The bilateral SLF I finding in both the BPD and AR-BPD groups may
      represent a trait-based marker or endophenotype of the disorder. The finding of
      decreased FA in the right and left CG-PAC(WM) in children with BPD compared to
      the other two groups may represent a disease-state related finding.

PMID- 18076530
TI  - Brain systems underlying response flexibility in healthy and bipolar adolescents:
      an event-related fMRI study.
AB  - OBJECTIVES: Previous studies have indicated abnormalities in response flexibility
      in pediatric bipolar disorder (BD). Dysfunction in response flexibility may
      contribute to the pattern of behavioral and emotional dysregulation that is
      characteristic of BD, since depressed and manic patients respond inflexibly to
      emotional stimuli (i.e., anhedonia in the case of depression or inappropriate
      positive affect in the case of mania). The present study was undertaken to
      determine if neuronal responses differed between BD and control subjects on a
      simple motor response flexibility task. METHODS: To elucidate the neural
      substrates mediating response flexibility in pediatric BD, we studied 25 youth
      with BD and 17 age-, gender- and IQ-matched controls (CON) as they performed the
      change task while undergoing event-related functional magnetic resonance imaging
      (fMRI). The change task is a new fMRI task that requires subjects to both inhibit
      and replace a prepotent motor response with another motor response after the
      initial response has been cued. RESULTS: On correctly performed change trials
      relative to correctly performed go trials, BD patients generated significantly
      more activity in the left dorsolateral prefrontal cortex (DLPFC) and in the
      primary motor cortex than did healthy controls, even though performance levels
      did not differ across groups. CONCLUSIONS: These results indicate that functional
      deficits within the left DLPFC may mediate deficits in response flexibility in
      pediatric BD. This deficit may extend beyond the realm of motor control and also
      affect emotion regulation.

PMID- 18076531
TI  - Outcome following a first manic episode: cross-national US and Taiwan comparison.
AB  - OBJECTIVES: Bipolar disorder (BD) is recognized as a significant psychiatric
      condition worldwide, yet little is known about cross-national differences in the
      course of illness. This information might clarify features of the disorder that
      are illness versus culturally specific. Therefore, the aim of this study was to
      identify differential and shared outcome predictors in first-episode manic
      bipolar patients in Cincinnati, OH, USA and Taipei, Taiwan. METHODS: DSM-IV
      bipolar patients were identified at the time of their first manic or mixed
      episode and were prospectively followed in a naturalistic, longitudinal study for
      one year. Patients were recruited from a first psychiatric hospitalization at
      university-affiliated, urban hospitals in Taipei and Cincinnati. The primary
      outcome measures were remission, recovery, recurrence and percent of follow-up
      spent with affective symptoms and syndromes. Treatment adherence was also
      assessed, as were a number of possible mediator variables. RESULTS: The two
      patient groups showed a number of significant differences in index clinical
      presentation on characteristics previously associated with outcome in other
      studies (e.g., substance abuse). The patients in Taipei showed significantly
      better outcome on virtually all measures. Some of these findings reflected
      differences in index (mediator) variables, whereas others persisted after
      controlling for potential baseline confounds. CONCLUSIONS: The early course of BD
      varies between Chinese and American patients. Some of this variance results from
      demographic and clinical cross-national differences in premorbid variables. Other
      sources of variance remain to be identified.

PMID- 18076532
TI  - The early manifestations of bipolar disorder: a longitudinal prospective study of
      the offspring of bipolar parents.
AB  - OBJECTIVE: A major aim of this longitudinal high-risk study is to identify
      reliable early indicators of emerging bipolar disorder (BD) among offspring from
      well-characterized parents. METHODS: High-risk offspring were recruited from
      families in which one parent had BD diagnosed on the basis of the Schedule for
      Affective Disorders and Schizophrenia - Lifetime version (SADS-L) interviews and
      DSM-IV diagnostic criteria and the other parent was well. Bipolar parents were
      further subdivided on the basis of response or non-response to long-term lithium.
      A comparison group of offspring was recruited from well parents diagnosed on the
      basis of either SADS-L interviews or the family history method. All consenting
      offspring from high-risk and control families were assessed longitudinally with
      the Schedule for Affective Disorders and Schizophrenia for School-aged Children -
      Present and Lifetime version (KSADS-PL) interviews and DSM-IV diagnoses were made
      on a blind consensus review. The offspring were reassessed on average annually,
      as well as at any time symptoms developed. RESULTS: Antecedent conditions to BD
      in both high-risk groups included sleep and anxiety disorders, while attention
      deficit hyperactivity disorder and pre-psychotic conditions were antecedents
      among the offspring of lithium non-responders only. Among those offspring
      developing BD, the index mood episode was almost always depressive. CONCLUSIONS:
      Despite a specific genetic risk, BD began with non-specific psychopathology
      and/or depressive disorders in a majority of offspring. Therefore, diagnosis
      based only on cross-sectional assessment of symptoms appears to be insufficient
      for the accurate early detection of emerging BD. Other parameters such as family
      history and associated antecedents should be taken into account.

PMID- 18076533
TI  - Factors associated with mental health service utilization among bipolar youth.
AB  - OBJECTIVES: This study aims to characterize patterns of mental health service
      utilization within a sample of bipolar youth. Demographic variables, youth
      bipolar characteristics, youth comorbid conditions, and parental psychopathology
      were examined as predictors of treatment utilization across different levels of
      care. METHODS: A total of 293 bipolar youth (aged 7-17 years) and their parents
      completed a diagnostic interview, family psychiatric history measures, and an
      assessment of mental health service utilization. Demographic and clinical
      variables were measured at baseline and mental health service use was measured at
      the six-month follow-up. RESULTS: Approximately 80% of bipolar youth attended
      psychosocial treatment services over the span of 6 months. Of those who attended
      treatment, 67% attended only outpatient services, 22% received inpatient/partial
      hospitalization, and 12% received residential/therapeutic school-based services.
      Using multinomial logistic regression, older age, female gender, and bipolar
      characteristics, including greater symptom severity and rapid cycling, were found
      to predict higher levels of care. Youth suicidal and non-suicidal self-injurious
      behavior, comorbid conduct disorder, and parental substance use disorders also
      predicted use of more restrictive treatment settings. CONCLUSIONS: Results
      underscore the importance of assessing for and addressing suicidality, comorbid
      conduct disorder, and parental substance use disorders early in the treatment of
      bipolar youth to potentially reduce the need for more restrictive levels of care.

PMID- 18076534
TI  - Antidepressant-associated switches from depression to mania in severe bipolar
      disorder.
AB  - OBJECTIVES: To determine whether switching from depression to mania is part of
      the natural history of bipolar illness or results from antidepressant (AD)
      treatment by examining bipolar patients with psychosis early in their illness
      course. METHODS: A multi-facility cohort of 123 first-admission inpatients, aged
      15-60 years, with DSM-IV bipolar disorder (BD) with psychotic features, was
      followed for four years, and 76 individuals experienced at least one episode of
      depression. Frequency of and risk factors for switches from depression to mania,
      time to switch, and duration of the subsequent manic episode were examined in
      relation to AD use (with anti-manic and/or antipsychotic medications). RESULTS:
      The 76 respondents experienced 113 depressive episodes. Those prescribed ADs had
      more depressive episodes and spent more time depressed than non-users. A total of
      23 depressive episodes in 17 respondents ended in a manic/hypomanic/mixed episode
      (20%). The time to switch and duration of the subsequent manic episode were not
      significantly different for the seven respondents and nine episodes involving AD
      treatment versus the 10 respondents and 14 episodes without ADs. None of the risk
      factors (age of onset <or=18 years, childhood psychopathology, depressive first
      episode, substance abuse at index admission, bipolar family history, type of AD
      used) was associated with switching. CONCLUSIONS: In this sample with severe BD,
      switching from depression to mania was not associated with AD treatment.
      Respondents who experienced switching appeared to have a more relentless form of
      BD. In only a few did ADs appear to be responsible for the switch.

PMID- 18076535
TI  - Bipolar disorder not otherwise specified in relation to the bipolar spectrum.
AB  - BACKGROUND: The purpose of this study was to determine the clinical
      characteristics of patients who are diagnosed with bipolar disorder not otherwise
      specified (BPD NOS) and who are considered to represent part of the bipolar
      spectrum. The lifetime prevalence of BPD in the general population may be as high
      as 6% when the full spectrum of bipolar disorders is accounted for. Correct
      identification of true bipolar patients in clinical settings may result in more
      appropriate treatment. Our hypothesis was that patients with BPD NOS would be
      more similar to other bipolar patients than major depressive disorder (MDD)
      patients in terms of age of onset, history of suicidal behavior and family
      history of BPD. METHODS: We conducted a retrospective chart review to extract and
      analyze data on the family history, disease course and clinical characteristics
      of 305 bipolar disorder I (BPD I), bipolar disorder II (BPD II), bipolar disorder
      not otherwise specified (BPD NOS) or major depressive disorder (MDD) patients who
      were then grouped by diagnosis for analysis. Nominal variables were compared
      between groups using chi-square tests and ANOVA was used to compare means between
      groups for continuous variables. Significant F values were followed by
      independent-samples t-tests. RESULTS: Patients with BPD I, BPD II and BPD NOS
      were all found to have a significantly earlier mean age of onset of depression
      than MDD patients. A significantly higher incidence of bipolar illness in a first
      degree relative was found in all BPD groups (27-32%) compared with MDD patients
      (11%). Only the BPD I group had a significantly higher rate of suicide attempts
      (42%), compared with the BPD NOS (17%) and MDD recurrent (16%) groups.
      CONCLUSIONS: Our data support the conclusions of others that an early age of
      onset and a positive family history of bipolar illness are associated not only
      with BPD I and II but also with 'softer' forms of bipolar illness, which DSM-IV
      classifies as BPD NOS and the current literature refers to as a category of
      'bipolar spectrum disorder', albeit with varying proposed definitions and
      diagnostic criteria. Suicide attempt history may be more useful in identifying
      the severity of illness than distinguishing the bipolar spectrum from depressive
      disorders. Further research is needed to clearly define the boundaries of the
      bipolar spectrum.

PMID- 18076536
TI  - Cognitive impairment in later life in patients with early-onset bipolar disorder.
AB  - OBJECTIVES: Cognitive impairment may interfere with psychosocial functioning in
      bipolar disorder (BD). There is limited information regarding the cognitive
      function of elderly bipolar patients with onset at a young age. The present study
      aimed to investigate the frequency and the determinants of cognitive impairment
      in elderly early-onset bipolar patients. METHODS: Using the Clock-drawing Test
      (CDT), the Mini Mental State Examination (MMSE), and the Cognitive Abilities
      Screening Instrument (CASI), we examined euthymic patients with bipolar I
      disorder in Taiwan, aged 60 years and older. Clinical data were obtained by
      reviewing medical records and personal interviews with patients and their family
      members. The onset of BD prior to the age of 40 years is defined as 'early
      onset'. RESULTS: Of the 52 early-onset patients, 42.3% were determined to have
      cognitive impairment by exhibiting either abnormal CDT or education-adjusted MMSE
      scores. In a multiple regression model, years of education and the age at the
      last manic/hypomanic (but not depressive) episode accounted for the greatest
      variance in both MMSE and CASI scores. While educational level and the age at the
      last manic/hypomanic episode were not considered in the regression model, onset
      with depressive syndrome and current age explained 21.5% of the variance in MMSE
      scores. Age at the first depressive episode, the first manic episode before the
      age of 40 years, and comorbid diabetes accounted for 16.7% of the variance in
      CASI scores. CONCLUSIONS: There appeared to be a sizable proportion of elderly
      early-onset bipolar patients having cognitive impairment. It is suggested that
      clinical manifestation of first-onset affective episode and impact of medical
      comorbidity affect the cognition of early-onset BD in later life.

PMID- 18076537
TI  - A near-infrared spectroscopy study of prefrontal cortex activation during a
      verbal fluency task and carbon dioxide inhalation in individuals with bipolar
      disorder.
AB  - OBJECTIVES: There is evidence of prefrontal cortex (PFC) dysfunction in patients
      with bipolar disorder (BP). Magnetic resonance and neuropathological studies show
      abnormalities of the brain microvasculature in patients with BP. However, the
      underlying biological mechanisms are not well understood. We investigated the
      relationship between activation of the PFC during a cognitive task and the
      vascular function in response to a physiological task in patients with BP.
      METHODS: Fourteen euthymic patients with BP and 14 control subjects matched for
      age, sex, and education were recruited. We examined the response of the PFC
      during a verbal fluency task and during 5% CO(2) inhalation using a 24-channel
      near-infrared spectroscopy imaging system to measure alteration of oxygenated and
      deoxygenated hemoglobin. RESULTS: The BP patients showed a significantly lower
      level of PFC activation during the cognitive task compared to the healthy
      controls, but the task-performance of the BP patients was not significantly
      different from that of the controls. The vascular response of the BP patients to
      CO(2) was not significantly different from that of controls. CONCLUSIONS: This
      study suggests functional hypoactivation of the PFC during a cognitive load in
      patients with BP while they are in a euthymic state. The mechanism of this
      hypoactivation is different from that of vascular regulation in response to a
      physiological stimulus.

PMID- 18076538
TI  - Rapid tryptophan depletion as a treatment for acute mania: a double-blind, pilot
      controlled study.
AB  - OBJECTIVES: Rapid reduction of up to 80% in plasma tryptophan level can be
      accomplished by administering an oral tryptophan-free amino acid solution, which
      induces hepatic protein synthesis and thereby depletes available plasma
      tryptophan. Rapid tryptophan depletion (RTD) has been shown to induce transient
      depressive symptoms in patients with remitted major depression. The effect of RTD
      in acutely manic patients has not been studied. METHODS: We carried out a double
      blind, placebo-controlled pilot study of RTD in acutely manic patients. Patients
      were randomized to the treatment groups. Sodium valproate treatment was started
      at a dose of 1,000 mg/day and continued throughout the 7-day study. On days 1-7,
      patients received a daily tryptophan-free amino acid drink or a placebo drink.
      The tryptophan-free amino acid drink contained a mix of amino acids without
      tryptophan. The placebo drink contained the additives and constituents of the
      real mixture to provide identical flavor and texture without the amino acids.
      Ratings were administered at baseline and then repeated on days 3, 5, and 7. All
      ratings were carried out by an experienced rater who was blind to the group
      assignment of patients. RESULTS: A total of 23 patients entered the study and 17
      completed the 7-day treatment protocol. The patients who received the amino acid
      drink showed greater improvement in mania ratings. The differences in Young Mania
      Rating Scale (YMRS) and Clinical Global Impression (GCI) scores were significant.
      However, the intolerance rate was high (23%) and the findings in this pilot study
      are based only on results from those patients who were able to tolerate the
      drink. CONCLUSIONS: Rapid tryptophan depletion may have an antimanic effect.

PMID- 18076539
TI  - A prospective open-label treatment trial of ziprasidone monotherapy in children
      and adolescents with bipolar disorder.
AB  - OBJECTIVE: To assess the effectiveness and tolerability of ziprasidone for
      treating pediatric mania. METHODS: This was an eight-week, open-label,
      prospective study of ziprasidone monotherapy (57.3 +/- 33.9 mg/day) in 21 bipolar
      youth [manic, mixed, or bipolar not otherwise specified (NOS); 6-17 years old].
      Assessments included the Young Mania Rating Scale (YMRS), Clinical Global
      Impressions-Improvement scale (CGI-I), and Brief Psychiatric Rating Scale (BPRS).
      Adverse events were assessed through spontaneous self-reports, vital signs,
      weight monitoring, and laboratory analysis. RESULTS: Fourteen of the 21 youth
      (67%) completed the study. Ziprasidone treatment was associated with clinically
      and statistically significant improvement in mean YMRS scores (-10.8 +/- 8.4, p <
      0.0001) and 57% had a CGI-I <or=2 at endpoint. Ziprasidone was well tolerated
      with no statistically significant increase in body weight (0.6 +/- 0.4 kg, p =
      0.2) or QTc interval (-3.7 +/- 4.7, p = 0.5). CONCLUSIONS: Open-label ziprasidone
      treatment was associated with a significant short-term improvement of symptoms of
      pediatric bipolar disorder. Future placebo-controlled, double-blind studies are
      warranted.

PMID- 18076540
TI  - Prevalence of the Child Behavior Checklist-pediatric bipolar disorder phenotype
      in a German general population sample.
AB  - BACKGROUND: In children with pediatric bipolar disorder (PBD), a consistent
      pattern of elevations in inattention/hyperactivity, depression/anxiety, and
      aggression has been identified on the Child Behavior Checklist (CBCL-PBD
      profile). In Germany, no epidemiological study has included PBD to date.
      OBJECTIVES: To estimate the six-month prevalence of the CBCL-PBD profile in
      Germany in a large normative general population sample, and to examine subjects
      with CBCL-PBD profile with regard to symptoms assumed to coexist with PBD (e.g.,
      suicidality, decreased need for sleep, and hypersexuality). METHODS: We studied a
      nationwide representative general population sample of 2,856 children and
      adolescents aged 4-18 years. RESULTS: A total of 21 subjects [0.7% of the sample;
      95% confidence interval (CI) = 0.5-1.1] met the criteria for the CBCL-PBD
      phenotype. CBCL-PBD subjects were more pervasively disturbed than clinical
      controls (n = 118; 4.1% of total sample; 95% CI = 3.4-4.9), demonstrated in
      significantly more social problems and delinquent behavior, and showed
      significantly higher rates of suicidality, decreased need for sleep and
      hypersexual behavior. CONCLUSIONS: The prevalence of CBCL-PBD subjects in the
      general German population compares to rates of PBD in US and Dutch
      epidemiological samples. Regardless of whether these subjects are affected by
      'real' PBD or 'severe, pervasive ADHD' with pronounced emotional dysregulation,
      they constitute a group of seriously disturbed children and adolescents. The high
      rate of suicidality among CBCL-PBD subjects emphasizes the need for the
      identification and adequate treatment of children meeting this profile.

PMID- 18076541
TI  - Psychotic features in bipolar and unipolar depression.
AB  - BACKGROUND: While some prior studies have found higher rates of psychotic
      depression in those with bipolar disorder or a bipolar relative, others have
      failed to confirm these observations. We examined the relationship of psychotic
      depression to polarity in several large familial samples of mood disorder.
      METHODS: A total of 4,724 subjects with major mood disorder in three family
      studies on the genetics of bipolar I disorder (BPI) or recurrent major depressive
      disorder (MDDR) were administered semi-structured interviews by clinicians.
      Determination of psychotic features was based on a report of hallucinations
      and/or delusions during the most severe depressive episode in the Schedule for
      Affective Disorders and Schizophrenia-Lifetime Version or the Diagnostic
      Interview for Genetic Studies interview. Rates of psychotic depression were
      calculated by diagnostic category and comparisons were made between diagnoses
      within and across studies using the generalized estimating equation. RESULTS: A
      diagnosis of BPI disorder was strongly predictive of psychotic features during
      depression compared to MDDR [odds ratio (OR) = 4.61, p < 0.0005]. Having bipolar
      II compared to MDDR was not predictive of psychosis (OR = 1.05, p = 0.260), nor
      was having a family history of BPI in MDDR subjects (OR = 1.20, p = 0.840).
      CONCLUSIONS: Psychotic features during a depressive episode increased the
      likelihood of a BPI diagnosis. Prospective studies are needed to confirm these
      findings. The potential genetic underpinnings of psychotic depression warrant
      further study.

PMID- 18076542
TI  - Phenomenology of mixed states: a principal component analysis study.
AB  - OBJECTIVES: To contribute to the definition of external and internal limits of
      mixed states and study the place of dysphoric symptoms in the psychopathology of
      mixed states. METHODS: One hundred and sixty-five inpatients with major mood
      episodes were diagnosed as presenting with either pure depression, mixed
      depression (depression plus at least three manic symptoms), full mixed state
      (full depression and full mania), mixed mania (mania plus at least three
      depressive symptoms) or pure mania, using an adapted version of the Mini
      International Neuropsychiatric Interview (DSM-IV version). They were evaluated
      using a 33-item inventory of depressive, manic and mixed affective signs and
      symptoms. RESULTS: Principal component analysis without rotation yielded three
      components that together explained 43.6% of the variance. The first component
      (24.3% of the variance) contrasted typical depressive symptoms with typical
      euphoric, manic symptoms. The second component, labeled 'dysphoria', (13.8%) had
      strong positive loadings for irritability, distressing sensitivity to light and
      noise, impulsivity and inner tension. The third component (5.5%) included
      symptoms of insomnia. Median scores for the first component significantly
      decreased from the pure depression group to the pure mania group. For the
      dysphoria component, scores were highest among patients with full mixed states
      and decreased towards both patients with pure depression and those with pure
      mania. CONCLUSIONS: Principal component analysis revealed that dysphoria
      represents an important dimension of mixed states.

PMID- 18076543
TI  - Complicated grief and impaired sleep in patients with bipolar disorder.
AB  - OBJECTIVES: To examine the relationship of sleep disturbance with complicated
      grief (CG) in patients with bipolar disorder (BD). METHODS: Adults with DSM-IV BD
      were asked if they ever experienced significant loss and, if so, completed the
      Inventory of Complicated Grief. Subjective sleep disturbance was assessed with
      the Pittsburgh Sleep Quality Index (PSQI). The association of CG with sleep
      disturbance was assessed in univariate t-tests, and in multivariate analyses
      controlling for the presence of anxiety disorder comorbidity and current bipolar
      recovery status. RESULTS: Individuals with CG had significantly higher mean PSQI
      scores (10.9 versus 7.9, p = 0.003) than those without CG. Further, within the
      group of BD participants who had experienced a significant loss, those with CG
      had significantly poorer sleep (p = 0.01). CG remained significantly associated
      with greater sleep impairment after adjustment for comorbid anxiety disorder and
      bipolar mood state. This additive impairment in sleep with CG comorbidity was
      evident for four of the PSQI component scales: sleep quality, sleep duration,
      sleep efficiency and sleep disturbance. CONCLUSIONS: Our data indicate a
      significant association of CG with poor sleep in individuals with BD. Disturbed
      sleep may be a mechanism by which CG increases the burden of illness in BD.

PMID- 18076544
TI  - Light therapy for bipolar disorder: a case series in women.
AB  - OBJECTIVES: To perform a dose-ranging safety and efficacy study of bright light
      therapy for depression in women with bipolar disorder (BD). METHODS: Nine women
      with DSM-IV BD I or II in the depressed phase were exposed to 50 lux (illuminance
      at the receiving surface) red light for two weeks, after which they received
      7,000 lux light therapy for two-week epochs of 15, 30 and 45 min daily. The
      Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical
      Depression Supplement and the Mania Rating Scale were used to assess mood
      symptoms. Four patients received morning light and five patients received midday
      light. RESULTS: Three of the four subjects treated with morning light developed
      mixed states. The fourth subject achieved a full, sustained response. To decrease
      the risk of inducing mixed episodes, we changed the time of light exposure to
      midday. Of the five women who received midday light therapy, two achieved full
      response and two showed early improvement but required a dose increase to sustain
      response. One woman remained depressed with 45 min of midday light but responded
      fully to a switch to morning light, 30 min daily. CONCLUSIONS: Women with bipolar
      illness are highly sensitive to morning bright light treatment; the induction of
      mixed states is a substantial risk. Initiating treatment with a brief duration
      (15 min) of midday light for bipolar depression is advisable.

PMID- 18076545
TI  - A unique consideration regarding medication compliance for bipolar affective
      disorder: exercise performance.

PMID- 18076547
TI  - Editorial: Dracunculiasis eradication by 2009: will endemic countries meet the
      target?

PMID- 18076548
TI  - Sleeping hearts: the role of the heart in sleeping sickness (human African
      trypanosomiasis).
AB  - OBJECTIVES: To estimate the frequency and evolution of heart involvement in human
      African trypanosomiasis (HAT) using electrocardiogram (ECG) findings; to describe
      these findings and to assess the frequency and clinical relevance of symptoms and
      signs before and after treatment. METHODS: In a prospective cohort study ECG
      findings, signs and symptoms consistent with heart failure and cardiac laboratory
      parameters were studied at baseline, 2 days after the end of treatment and 3
      months later. RESULTS: Major ECG alterations were significantly more frequent in
      HAT patients than in healthy controls (71%vs. 18%; P < 0.001); 31% were low
      voltage changes, 34% were repolarization changes. ECG signs of necrosis and
      conduction problems were rare. Symptoms consistent with heart failure such as
      exertional dyspnoea (19%vs. 1.7%; P = 0.002) or palpitations (18%vs. 5%; P =
      0.28) occurred more frequently in patients than in controls. The median NT-proBNP
      was significantly higher in HAT patients than in controls (85.2 vs. 28 pg/ml; P <
      0.001). Troponin levels were normal. At the end of treatment repolarization
      changes appeared or worsened in 33.4%. Such changes improved or disappeared at
      follow-up in 33.1% of the patients. CONCLUSIONS: Cardiac involvement documented
      by ECG alterations is common in HAT patients, but cardiopathy rarely causes
      severe congestive heart failure and subsides after treatment. ECG alterations
      immediately after treatment and their improvement 3 months later may be the
      result of a treatment-induced inflammatory reaction.

PMID- 18076549
TI  - Macrofilaricidal effect of 4 weeks of treatment with doxycycline on Wuchereria
      bancrofti.
AB  - OBJECTIVE: To evaluate the efficacy of doxycycline as a macrofilaricidal agent
      against Wuchereria bancrofti. METHOD: In the Western Region of Ghana, 18 patients
      infected with W. bancrofti were recruited and treated with 200 mg doxycycline per
      day for 4 weeks. Seven untreated patients served as controls. Four months after
      doxycycline treatment, all patients received 150 mug/kg ivermectin. Patients were
      monitored for Wolbachia and microfilaria loads, antigenaemia and filarial dance
      sign (FDS). RESULTS: Four months after doxycycline treatment, cases had a
      significantly lower Wolbachia load than controls; and 24 months after treatment,
      microfilaraemia, antigenaemia and frequency of FDS were significantly lower in
      cases than controls. Most importantly, 4 weeks of doxycycline killed 80% of
      macrofilariae, which is comparable with the results of a 6-week regimen.
      Circulating filarial antigenaemia and FDS were strongly correlated. CONCLUSION: A
      4-week regimen of doxycycline seems sufficient to kill adult W. bancrofti and
      could be advantageous for the treatment of individual patients, e.g. in
      outpatient clinics.

PMID- 18076550
TI  - Hepatosplenomegaly in Kenyan schoolchildren: exacerbation by concurrent chronic
      exposure to malaria and Schistosoma mansoni infection.
AB  - OBJECTIVES: Chronic exposure to malaria exacerbates Schistosoma mansoni
      associated hepatosplenomegaly in school-aged children. However, residual
      hepatosplenomegaly after treatment of S. mansoni with concurrent mollusciciding
      suggests malaria could be an underlying cause of hepatosplenomegaly. We
      investigated the role of chronic malaria in childhood hepatosplenomegaly in the
      presence and absence of concurrent S. mansoni infection. METHODS: Cross-sectional
      study of children in an study area where transmission of S. mansoni, but not
      malaria, is restricted to the eastern end. Clinical and ultrasound examinations
      were conducted, and parasitological and serological tests used to determine S.
      mansoni infection intensities and comparative exposure levels to malaria.
      RESULTS: Chronic exposure to malaria, as determined by Pfs-IgG3 levels, was
      associated with hepatosplenomegaly even in the absence of S. mansoni infection.
      Children infected with S. mansoni mostly had light to moderate infection
      intensities but greater enlargement of the liver and spleen than children who did
      not have schistosomiasis, and for the left liver lobe this was S. mansoni
      infection intensity dependent. CONCLUSIONS: Children chronically exposed to
      malaria but without S. mansoni infection can have hepatosplenomegaly, which even
      light S. mansoni infections can exacerbate in an intensity-dependent manner.
      Thus, concurrent chronic exposure to S. mansoni and Plasmodium falciparum can
      have an additive or synergistic effect on childhood morbidity.

PMID- 18076551
TI  - Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C
      reactive protein in monitoring leprosy patients during multi-drug treatment and
      reactions.
AB  - OBJECTIVE: To verify the validity of measuring the levels of Mycobacterium leprae
      specific anti-phenolic glycolipid (PGL)-I antibody, neopterin, a product of
      activated macrophages, and C-reactive protein (CRP), an acute phase protein, in
      serial serum samples from patients for monitoring the leprosy spectrum and
      reactions during the course of multi-drug treatment (MDT). METHODS: Twenty-five
      untreated leprosy patients, 15 multi-bacillary (MB) and 10 paucibacillary (PB),
      participated. Eight patients developed reversal reaction and five developed
      erythema nodosum leprosum (ENL) during follow-up. The bacterial index (BI) in
      slit-skin smears was determined at diagnosis and blood samples collected by
      venipuncture at diagnosis and after 2, 4, 6 and 12 months of MDT. PGL-I antibody
      and neopterin were measured by enzyme-linked immunosorbent assay, whereas the CRP
      levels were measured by the latex agglutination method. RESULTS: The levels of
      PGL-I antibodies and neopterin were higher in the sera of MB than PB patients,
      which correlated with the patients' BI. The serum levels of CRP did not differ
      significantly between the MB and PB patients. The serum levels of PGL-I and
      neopterin were no higher in reactional patients than non-reactional patients
      prone to such reactions. However, ENL patients had higher serum CRP levels than
      non-reactional MB patients. The serum PGL-I antibody levels declined
      significantly during MDT, in contrast to neopterin and CRP levels. CONCLUSION:
      Measuring the serum levels of PGL-I antibodies and neopterin appeared to be
      useful in distinguishing MB from PB patients, whereas monitoring the levels of
      PGL-I antibodies appeared to be useful in monitoring MB patients on MDT.
      Measuring serum CRP, although not useful in monitoring the patients, has limited
      significance in detecting ENL reactional patients.

PMID- 18076552
TI  - Same-day smears in the diagnosis of tuberculosis.
AB  - OBJECTIVE: To assess the feasibility of completing the diagnosis of tuberculosis
      (TB) in 1 day by collecting only on-the-spot specimens. METHODS: Individuals with
      suspected TB attending district hospitals in Abuja submitted three sputum samples
      for routine diagnosis (the standard approach). One additional sample was
      collected 1 h after the first sputum (the same-day approach). One sputum sample
      was cultured. Blood samples were tested for HIV. RESULTS: Two hundred and twenty
      four patients with chronic cough had 135/672 (20%) positive on-the-spot smears
      and 47/224 (21%) positive morning smears. The same-day and internationally
      recommended approaches identified 44 and 45 of the 78 patients with positive
      cultures, respectively. 106/194 (55%) patients were HIV positive. Only 9-11% of
      their smears were positive compared with 30-32% for HIV negatives (P < 0.01).
      CONCLUSION: It could be possible to diagnose TB in a single day by examining two
      spot specimens, but the feasibility needs to be confirmed on a larger scale.

PMID- 18076553
TI  - How affordable are tuberculosis diagnosis and treatment in rural China? An
      analysis from community and tuberculosis patient perspectives.
AB  - OBJECTIVES: To assess equity in access to tuberculosis (TB) care by estimating
      and comparing the direct household costs perceived by community residents with
      actual costs experienced by TB patients and to identify the factors influencing
      the financial burden of TB patients. METHODS: Economic study in four provinces of
      China by means of a survey of 889 TB patients and 2560 community residents and in
      depth interviews with key informants. RESULTS: The direct household costs for
      using TB health services perceived by the communities were two to five times
      higher than the actual costs incurred by the TB patients. Patients had to pay a
      substantial proportion of their annual income for TB services (12-40%), despite
      the fact that smear-positive and some severe smear-negative patients received
      free drugs. Repeated outpatient visits before diagnosis, over-prescription of
      drugs and prolonged treatments were common. CONCLUSIONS: The heavy financial
      burden (both perceived and real) on these patients is one of the main reasons
      that some TB patients fail to access and complete treatment. Pressure to generate
      revenue through current incentives in health-care financing and poor competence
      of health workers at the village and township levels cause delay and high
      expenses to TB patients and ultimately impede effective TB control in China.

PMID- 18076554
TI  - Short communication: CD4 counts of HIV-infected pregnant women and their infected
      children--implications for PMTCT and treatment programmes.
AB  - A considerable proportion of pregnant women and their infected children are
      likely to be eligible for anti-retroviral treatment. The antenatal-postnatal
      divide needs to be bridged with respect to the follow-up of both HIV-infected
      women and their exposed infants.

PMID- 18076555
TI  - Determinants of HIV counselling and testing participation in a prevention of
      mother-to-child transmission programme in rural Burkina Faso.
AB  - OBJECTIVES: To analyse the factors associated with the uptake of HIV counselling,
      HIV testing and returning for test results in a rural hospital setting in Nouna,
      Burkina Faso. METHODS: Cross sectional survey of 435 pregnant women who visited
      the district hospital for antenatal care, from July to December 2004. Separate
      multivariate logistic regression analyses including analysis of reported reasons
      were performed to identify the factors associated with accepting HIV counselling
      and testing. RESULTS: HIV testing participation was related to discussing HIV
      screening with the partner (OR 8.36), and the number of antenatal care (ANC)
      visits already accomplished (OR 2.23). The quality of pre-test counselling was
      very poor as 42% did not understand the process. The absence of doctors and
      mismanagement of time for post-test counselling were the main reasons why women
      did not receive test results. Analysis of participants by discussion status,
      counselling and test participation revealed that fewer women dropped out at every
      stage who discussed HIV testing with their partner. CONCLUSION: Communication
      with the partner plays a vital role in the uptake of HIV testing. Encouraging
      women to engage in a discussion about testing with their partners may be a viable
      intervention to improve participation. Quality of service needs to be better.

PMID- 18076556
TI  - Missed opportunities to address reproductive health care needs among HIV-infected
      women in antiretroviral therapy programmes.
AB  - OBJECTIVES: To investigate the delivery of reproductive health care services in
      an antiretroviral therapy (ART) programme in Cape Town, South Africa. METHODS: A
      cross-sectional survey was conducted among 227 consecutive women attending a
      hospital-based ART outpatient service who had been on ART for at least one month.
      Semi-structured interviews investigating reproductive health issues and services
      received were conducted in participants' home language by a trained interviewer.
      RESULTS: Sixty-seven per cent of the women were younger than 30 years and 75%
      were sexually active. The use of both condoms (70%) and hormonal contraceptives
      (31%) decreased with age, while the prevalence of sterilization (13%) increased
      with age. Few women knew about emergency contraception (EC) (7%) or termination
      of pregnancy (TOP) (13%). Approximately 45% of women had had a Papanicolau smear,
      and this was constant across all age groups. One in 10 women had experienced
      verbal or physical abuse by an intimate partner since their HIV diagnosis. More
      than 80% of women had discussed the use of condoms and other forms of
      contraception with a health care provider since their HIV diagnosis, but less
      than 5% had discussed EC or TOP, and no woman had discussed issues of partner
      violence. Discussion These data delineate the large unmet need for reproductive
      health services among HIV-infected women receiving ART in this setting. While
      issues related to condom and contraceptive use are relatively well addressed,
      reproductive health services related to unintended pregnancy and partner violence
      appear to be neglected. The integration of a broad range of reproductive health
      services into ART programmes requires urgent attention in both research and
      policy-making circles.

PMID- 18076557
TI  - Midwifery provision and uptake of maternity care in Indonesia.
AB  - OBJECTIVES: To examine the association between midwife density, other
      characteristics of midwifery provision and village contextual factors, and the
      percentage of births attended by a health professional and deliveries via
      caesarean section in two districts in West Java, Indonesia. METHODS: Analysis of:
      (i) a census of midwives; (ii) a population-based survey of women who had
      delivered over a 2-year period; (iii) a census of all caesareans in the four
      hospitals serving the two districts; and (iv) data from National Statistical
      Office. RESULTS: At an average density of 2.2 midwives per 10 000 population, 33%
      of births are with a health professional, and 1% by caesarean section. Having at
      least six midwives per 10 000 population was associated with a fourfold increase
      in caesareans [adjusted risk ratio (RR) 4.3: 95% confidence interval (CI): 3.3
      5.5] and a threefold increase in the odds of having a health professional attend
      the delivery [adjusted odds ratio (OR) 2.88: 95% CI: 0.96-8.70]. The assigned
      midwife's professional status and the duration of her service in the village were
      also associated with higher rates of health professionals' attendance of delivery
      and caesareans. Regardless of the provision of services, women's education and
      wealth were strong predictors of delivery with a health professional.
      CONCLUSIONS: Promoting a stable workforce of midwives, better financial access
      for the poor and expanding female education are important for the achievement of
      the fifth Millennium Development Goal (MDG-5).

PMID- 18076558
TI  - Risk factors and consequences of congenital Chagas disease in Yacuiba, south
      Bolivia.
AB  - OBJECTIVE: To determine the risk factors of congenital Chagas disease and the
      consequences of the disease in newborns. METHODS: Study of 2712 pregnant women
      and 2742 newborns in Yacuiba, south Bolivia. Chagas infection was determined
      serologically in mothers and parasitologically in newborns. Consequences of
      congenital Chagas disease were assessed clinically. RESULTS: The prevalence of
      Chagas disease in pregnant women was 42.2%. Congenital transmission was estimated
      at 6% of infected mothers leading to an incidence rate of 2.6% among newborns.
      Main risk factors of congenital transmission were mothers' seropositivity and
      maternal Trypanosoma cruzi parasitaemia. Parity was higher in infected than in
      non-infected mothers, but it was not associated with the risk of congenital
      transmission. The rate of congenital infection was significantly higher in
      newborns from multiple pregnancies than in singletons. However, we did not
      observe statistically significant consequences of Chagas disease in newborns from
      single pregnancies or among twins. CONCLUSIONS: The main risk factors for
      congenital transmission were infection and parasitaemia of mothers. Consequences
      of the disease seemed mild in newborns from single pregnancies and perhaps more
      important in multiple births.

PMID- 18076559
TI  - Infant mortality among twins and triplets in rural Bangladesh in 1975-2002.
AB  - To examine trends in incidence of multiple births (MB) and their survival in
      infancy, we used population-based, longitudinal data derived from the Health and
      Demographic Surveillance System in Matlab, Bangladesh, from 1975 to 2002.
      Logistic regression was applied to determine the impact of a number of variables
      on mortality among MB in the first year of life. MB averaged 2% of all live
      births, but contributed 10% to all infant deaths. Infant mortality among MB was
      more than five times higher than among singletons. Mortality among MB declined by
      27% in 1975-2002, considerably less than the 51% mortality decline among
      singletons in the same period. Infant mortality among twins and triplets was
      particularly high among children who were born to young mothers (<20 years), who
      were the first live birth, who were born after a short birth interval (<24
      months) and whose mothers were unschooled. Mortality of MB was lower in the area
      with easy access to high-quality maternal and child-care services. Thus, good
      maternity and newborn care will improve the survival of MB.

PMID- 18076560
TI  - Malaria and anaemia among pregnant women at first antenatal clinic visit in
      Kisumu, western Kenya.
AB  - OBJECTIVE: To determine the prevalence of malaria and anaemia among urban and
      peri-urban women attending their first antenatal clinic (ANC) in an area of
      perennial malaria transmission. METHODS: Between November 2003 and May 2004 we
      screened first ANC attenders for malaria and anaemia in a large urban hospital in
      Kisumu (western Kenya) and interviewed them to obtain demographic and medical
      information. RESULTS: Among the 685 study participants, prevalence of malaria
      parasitaemia was 18.0%, prevalence of any anaemia (haemoglobin < 11 g/dl) was
      69.1% and prevalence of moderate anaemia was (haemoglobin < 8 g/dl) 11.8%.
      Sixteen women were hospitalized during pregnancy, eight because of malaria. In
      multivariate analysis, young age, living in a house with mud walls, a visit to
      rural area, peri-urban residence, second trimester of pregnancy and Luo ethnicity
      were significant risk factors for malaria parasitaemia. Malaria was an important
      risk factor for any and moderate anaemia; use of an insecticide-treated net (ITN)
      was a protective factor for any anaemia. Married women with a higher level of
      education, better-quality housing and full-time employment were more likely to
      use an ITN. CONCLUSION: Malaria and anaemia are established problems by the time
      of the first ANC visit. Mechanisms to deliver ITNs to women of child-bearing age
      before they become pregnant need to be explored. Early ANC visits are warranted
      in order for women to benefit from policies aimed at reducing the burden of
      malaria and anaemia.

PMID- 18076561
TI  - Viewpoint: evaluating the impact of malaria control efforts on mortality in sub
      Saharan Africa.
AB  - OBJECTIVE: To describe an approach for evaluating the impact of malaria control
      efforts on malaria-associated mortality in sub-Saharan Africa, where disease
      specific mortality trends usually cannot be measured directly and most malaria
      deaths occur among young children. METHODS: Methods for evaluating changes in
      malaria-associated mortality are examined; advantages and disadvantages are
      presented. RESULTS: All methods require a plausibility argument-i.e., an
      assumption that mortality reductions can be attributed to programmatic efforts if
      improvements are found in steps of the causal pathway between intervention scale
      up and mortality trends. As different methods provide complementary information,
      they can be used together. We recommend following trends in the coverage of
      malaria control interventions, other factors influencing childhood mortality,
      malaria-associated morbidity (especially anaemia), and all-cause childhood
      mortality. This approach reflects decreases in malaria's direct and indirect
      mortality burden and can be examined in nearly all countries. Adding other
      information can strengthen the plausibility argument: trends in indicators of
      malaria transmission, information from demographic surveillance systems and
      sentinel sites where malaria diagnostics are systematically used, and verbal
      autopsies linked to representative household surveys. Health facility data on
      malaria deaths have well-recognized limitations; however, in specific
      circumstances, they could produce reliable trends. Model-based predictions can
      help describe changes in malaria-specific burden and assist with program
      management and advocacy. CONCLUSIONS: Despite challenges, efforts to reduce
      malaria-associated mortality in Africa can be evaluated with trends in malaria
      intervention coverage and all-cause childhood mortality. Where there are
      resources and interest, complementary data on malaria morbidity and malaria
      specific mortality could be added.

PMID- 18076562
TI  - Short communication: The cost-effectiveness of cutaneous leishmaniasis patient
      management during an epidemic in Chaparral, Colombia in 2004.
AB  - We calculated ranges for the cost per disability adjusted life year (DALY)
      averted for cutaneous leishmaniasis (CL) treatment during an ongoing epidemic of
      CL in Chaparral, Colombia. Using operational clinical and cost data, we
      calculated that the cost of treating leishmaniasis patients with standard
      pentavalent antimony was US$345 (95% CI 277-488) per patient treated and cured.
      The cost per DALY averted per patient cured with antimony was estimated to be
      approximately US$15 000 (95% CI 12 226-21 532).

PMID- 18076563
TI  - The relative contribution of case management and inadequate care-seeking
      behaviour to childhood deaths from diarrhoea and acute respiratory infections in
      Hidalgo, Mexico.
AB  - Objective To investigate the contribution of poor case management and care
      seeking behaviour to childhood deaths from acute respiratory infections (ARI) and
      diarrhoeal diseases in rural Mexico. Methods Eighty-nine deaths from ARI and
      diarrhoea in under-fives from Hidalgo over a 7-month period were identified from
      registered death certificates. We interviewed the carers of 75 of these children,
      eliciting what happened before death, including signs and symptoms, contact with
      health services, details on treatments and details of doctors. These death
      narratives were used to assess the contributions of care seeking and case
      management to the childhood deaths. We conducted an independent investigation of
      the clinical competence of doctors mentioned in the death narratives using
      standard case scenarios and compared this with results obtained from
      neighbourhood control doctors. Results Late care seeking and/or poor case
      management contributed to 68% of deaths. The estimated contribution of care
      seeking alone was 32%, of case management alone 17% and of both care seeking and
      case management 18% of deaths. Doctors implicated as having contributed to a
      child's death had significantly lower clinical competence scores than those who
      were not. Private doctors accounted for 1.4 times more consultations prior to
      death than public doctors, but were implicated in 1.8 times the number of deaths.
      Conclusion Efforts to reduce child mortality need to improve both care seeking
      for childhood illnesses and quality of case management. It is essential that
      doctors in the private sector be included, as in Mexico and many other countries
      they provide a large proportion of care, often with adverse outcomes.

PMID- 18076564
TI  - Incidence of primary dengue virus infections in Southern Vietnamese children and
      reactivity against other flaviviruses.
AB  - OBJECTIVE: To study the incidence of asymptomatic primary dengue infections among
      children and reactivity against other flaviviruses. METHODS: A total of 216
      children, who had no dengue-specific IgG antibodies during a serosurvey in 2003
      were re-examined 23 months later to determine if seroconversion had occurred.
      Dengue-specific IgG was demonstrated with enzyme-linked immunosorbent assay
      (ELISA) and reactivity patterns against other flaviviruses were assessed by using
      immunofluorescence assay (IFA). RESULTS: Sixty-six children had seroconverted for
      dengue virus-specific IgG; the true annual incidence of primary dengue was thus
      17.3% (95% CI: 13.8-21.4). Japanese Encephalitis virus (JEV)-specific IgG
      antibodies were detected by IFA among three (4.6%) samples that showed
      seroconversion in the dengue ELISA, because of cross-reactivity. CONCLUSION: Our
      findings highlight the high incidence of dengue among Vietnamese children; JEV
      infections are rare. The true annual incidence of dengue can be estimated with a
      single cross-sectional seroprevalence survey.

PMID- 18076565
TI  - Anne McLaren (1927-2007).

PMID- 18076567
TI  - Tel2: a common partner of PIK-related kinases and a link between DNA checkpoint
      and nutritional response?
AB  - A recent paper (Hayashi et al. 2007) in this issue of Genes to Cells shows that
      the fission yeast Schizosaccharomyces pombe Tel2, a homologue of mammalian/worm
      CLK2/Clk-2/Rad-5, physically interacts with all the phosphoinositide 3-kinase
      related kinases (PIKKs) that include Rad3/Tel1 (ATR/ATM homologues), Tor1/Tor2
      (TOR kinases) and Tra1/Tra2 (TRRAP homologues), raising the possibility that Tel2
      family proteins link various PIKK-related cellular processes by interacting with
      PIKK family proteins. In this minireview, implications and impact of the
      findings, and a possibility that PIKKs are functionally related through Tel2, are
      discussed.

PMID- 18076568
TI  - A new class of tissue-specifically methylated regions involving entire CpG
      islands in the mouse.
AB  - CpG islands, which have higher GC content and CpG frequencies compared to the
      genome as a whole, are generally believed to be unmethylated in tissues except at
      promoters of genes undergoing X chromosome inactivation or genomic imprinting.
      Recent studies, however, have shown that CpG islands at promoters of a number of
      genes contain tissue-dependent, differentially methylated regions (T-DMRs). In
      general, the tissue-specific methylation is restricted to a part of the promoter
      CpG island, with hypomethylation of the remaining sequence. In the current study,
      using comparison between Restriction Landmark Genomic Scanning (RLGS) and in
      silico RLGS, we identified ten sperm-specific unmethylated NotI sites, T-DMRs
      located in CpG islands that were hypomethylated in sperm but near-completely
      methylated in the kidney and brain. Unusually, these T-DMRs involve the whole CpG
      island at each of these loci. We characterized one of these genes, adenine
      nucleotide translocator 4 (Ant4), which is expressed in germ cells. Using a
      promoter assay, we demonstrated that expression of Ant4 gene is controlled by DNA
      methylation at the CpG island sequences within the promoter region. Ant4 and
      other sperm-specific hypomethylated loci represent a new class of CpG islands
      that become completely methylated in different cell lineages. T-DMRs at CpG
      islands are functionally important gene regulatory elements that may now be
      categorized into two classes: T-DMRs involving a subregion of the CpG island and
      those that occupy the whole CpG island.

PMID- 18076569
TI  - Regulation of the interaction of Disabled-1 with CIN85 by phosphorylation with
      Cyclin-dependent kinase 5.
AB  - Disabled-1 (Dab1) is an adaptor protein mediating Reelin signaling in neuronal
      migration during brain development. Cyclin-dependent kinase 5 (Cdk5)-p35 is a
      proline-directed Ser/Thr kinase also involved in neuronal migration. The
      interaction between Dab1 and Cdk5 is in need of investigation. Dab1 was
      phosphorylated at Ser400 and Ser491 by Cdk5 in vivo. We search for proteins that
      interact with Dab1 in a phosphorylation-dependent manner at these sites, and
      identified CIN85, an SH3-containing adaptor protein involved in endocytosis, and
      CPalpha/CPbeta, which are subunits of barbed end F-actin-capping proteins (CP),
      as proteins bound to unphosphorylated Dab1 by mass spectrometric analysis. It was
      shown that the PTPAPR sequence of Dab1, conforming to the PxxxPR atypical SH3
      binding motif, was the binding site for SH3 domains of CIN85. The results that
      phosphorylation at Ser491 close to the PTPAPR sequence inhibited association with
      CIN85 may provide a mechanism regulating the interaction between the PxxxPR motif
      proteins and SH3 domains of CIN85 family proteins. Together with previous results
      that CIN85 regulates actin assembly, present results raise the possibility that
      Cdk5 modulates actin dynamics through regulation of CIN85-Dab1 interaction by the
      Dab1 phosphorylation.

PMID- 18076570
TI  - Structural basis of PSGL-1 binding to ERM proteins.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1), an adhesion molecule with O
      glycosylated extracellular sialomucins, is involved in leukocyte inflammatory
      responses. On activation, ezrin-radixin-moesin (ERM) proteins mediate the
      redistribution of PSGL-1 on polarized cell surfaces to facilitate binding to
      target molecules. ERM proteins recognize a short binding motif, Motif-1,
      conserved in cytoplasmic tails of adhesion molecules, whereas PSGL-1 lacks Motif
      1 residues important for binding to ERM proteins. The crystal structure of the
      complex between the radixin FERM domain and a PSGL-1 juxtamembrane peptide
      reveals that the peptide binds the groove of FERM subdomain C by forming a beta
      strand associated with strand beta5C, followed by a loop flipped out towards the
      solvent. The Motif-1 3(10) helix present in the FERM-ICAM-2 complex is absent in
      PSGL-1 given the absence of a critical Motif-1 alanine residue, and PSGL-1
      reduces its contact area with subdomain C. Non-conserved positions are occupied
      by large residues Met9 and His8, which stabilize peptide conformation and enhance
      groove binding. Non-conserved residues play an important role in compensating for
      loss of binding energy resulting from the absence of conserved residues important
      for binding.

PMID- 18076571
TI  - Putative tumor suppressor EDD interacts with and up-regulates APC.
AB  - Adenomatous polyposis coli (APC), whose mutation causes colorectal cancers, is a
      key player in the Wnt signaling pathway. While the role of APC in inhibition of
      beta-catenin/LEF1-dependent activation of transformation-inducing genes has been
      intensively studied and well established, regulation of APC expression at the
      protein level is only partially understood. Here we report that APC is up
      regulated by EDD, the mammalian orthologue of Drosophila
      melanogaster"hyperplastic discs" gene (hyd) that is considered to be a putative
      tumor suppressor. Screening of APC immunocomplexes by mass spectrometry
      identified EDD as a putative APC-interacting protein. Exogenously expressed and
      endogenous APC interacted with EDD in vivo. Indirect immunofluorescent analyses
      demonstrated that APC and EDD co-localized in the cytoplasm of the cell. Over
      expression of EDD enhanced the protein expression level of APC and its binding
      partner Axin, resulting in inhibition of Wnt signaling downstream of beta
      catenin. Conversely, siRNA knock-down of EDD down-regulated APC at the protein
      level without altering its mRNA level, causing enhanced protein expression of
      beta-catenin. Thus, through protein-protein interaction, EDD stabilizes APC and
      up-regulates APC's function to inhibit beta-catenin, suggesting that EDD could
      act as a colorectal tumor suppressor.

PMID- 18076572
TI  - DNA supercoiling factor positively regulates expression of the homeotic gene
      Abdominal-B in Drosophila melanogaster.
AB  - DNA supercoiling factor (SCF) generates unconstrained negative supercoils of DNA
      in conjunction with eukaryotic topoisomerase II. In Drosophila melanogaster, SCF
      localizes to puffs on polytene chromosomes and is required for dosage
      compensation via hypertranscripton of genes on the male X chromosome. The present
      study investigated the role of SCF on autosomes. Although RNAi knockdown of scf
      results in male lethality, some escapers showed anterior homeotic transformation
      of the male sixth abdominal segment, similar to that arising from reduced
      expression of Abdominal-B (Abd-B). Heterozygotes for an scf mutant allele
      (scf(1)) displayed suppression of Pc mutation-dependent posterior transformation
      and enhancement of anterior transformation caused by trxG mutations. The level of
      Abd-B mRNA decreased in scf(1) embryos compared with wild-type. Tiling array
      experiments showed the presence of significant SCF signals in an Abd-B promoter
      region. Expression from the basal Abd-B promoter on a transgene was reduced in
      scf(1) embryos compared with wild-type. Collectively, these results demonstrate
      that SCF occupies the promoter region of Abd-B and activates expression for the
      proper formation of abdominal segments. Furthermore, preferential occupancy of
      SCF around transcription start sites of many active genes suggests a role for the
      factor in positive regulation of promoters.

PMID- 18076573
TI  - Rapamycin sensitivity of the Schizosaccharomyces pombe tor2 mutant and
      organization of two highly phosphorylated TOR complexes by specific and common
      subunits.
AB  - Nutrients are essential for cell growth and division. Screening of
      Schizosaccharomyces pombe temperature-sensitive strains led to the isolation of a
      nutrient-insensitive mutant, tor2-287. This mutant produces a nitrogen starvation
      induced arrest phenotype in rich media, fails to recover from the arrest, and is
      hypersensitive to rapamycin. The L2048S substitution mutation in the catalytic
      domain in close proximity to the adenine base of ATP is unique as it is the sole
      known genetic cause of rapamycin hypersensitivity. Localization of Tor2 was
      speckled in the vegetative cytoplasm, and both speckled and membranous in the
      arrested cell cytoplasm. Using mass spectroscopic analysis, we identified six
      subunits (Tco89, Bit61, Toc1, Tel2, Tti1 and Cka1) that, in addition to the six
      previously identified subunits (Tor1, Tor2, Mip1/Raptor, Ste20/Rictor, Sin1/Avo1
      and Wat1/Lst8), comprise the TOR complexes (TORCs). All of the subunits so far
      examined are multiply phosphorylated. Tel2 bound to Tti1 interacts with various
      phosphatidyl inositol kinase (PIK)-related kinases including Tra1, Tra2 and Rad3,
      as well as Tor1 and Tor2. Schizosaccharomyces pombe TORCs should thus be
      functionally redundant and might be broadly regulated through different subunits
      that are either common or specific to the two TORCs, or even common to various
      PIK-related kinases. Functional redundancy of the TORCs may explain the rapamycin
      hypersensitivity of tor2-287.

PMID- 18076574
TI  - Polycomb complexes regulate cellular senescence by repression of ARF in
      cooperation with E2F3.
AB  - Cellular senescence is a program in normal cells triggered in response to various
      types of stress that cells experience when they are explanted into culture. In
      this study, functional analyses on the role of the class II polycomb complex in
      cellular senescence were performed using mouse embryo fibroblasts (MEFs) with a
      genetically deleted member of the complex, Mel18. Mel18-null MEFs undergo typical
      premature senescence accompanied by the up-regulation of ARF/p53/p16(INK4a) and
      decrease of Ring1b/Bmi1. Our results demonstrated that ARF or p53 deletion
      cancels the senescence in Mel18-null MEFs, and the fact that p16(INK4a) is up
      regulated in double-null MEFs suggests that the ARF/p53 pathway plays a central
      role in stress-induced senescence. The in vivo binding of Ring1b and E2F3b to the
      ARF promoter decreased progressively in senescence, and Mel18 inactivation
      accelerated the exfoliation of Ring1b/E2F3b from the promoter sequence,
      indicating the cooperation of polycombs/E2F3b on ARF expression and cellular
      senescence. Taken together, it seems that class II polycomb proteins and E2F3b
      dually control cellular senescence via the ARF/p53 pathway.

PMID- 18076578
TI  - Determination of the minimum inhibitory concentration of four medicaments used as
      intracanal medication.
AB  - The aim of this study was to determine the minimum inhibitory concentration (MIC)
      of iodoform, calcium hydroxide, IKI (iodine potassium iodine) and CFC
      (ciprofloxacin, Flagyl (metronidazole) and calcium hydroxide) required to kill S.
      aureus, Pseudomonas aeruginosa, Enterococcus faecalis and B. fragilis. In the
      experiment, medicaments were added to bacterial species into test tubes, in 10
      different concentrations. The MIC was the lowest concentration of the drug at
      which bacterial growth could not be observed. In this investigation, CFC was the
      most effective medicament against all bacteria. All drugs were able to eliminate
      E. faecalis and B. fragilis, while IKI was not effective against S. aureus. IKI
      and calcium hydroxide were not able to eliminate P. aeruginosa as well.

PMID- 18076577
TI  - Comparative in vivo analysis of the sealing ability of three endodontic sealers
      in dog teeth after post-space preparation.
AB  - This study compared the sealing ability of RoekoSeal, AH Plus and EndoRez in dog
      premolars after post-space preparation and exposure to the oral environment.
      Seventy-four root canals were cleaned, shaped and filled with gutta-percha and
      one of the sealers. Post spaces were prepared with about 4-mm root canal filling
      remaining in the apex. Teeth were sealed for 24 h for sealer setting. Teeth were
      exposed to the oral environment for 45 days. The dogs were killed and root canals
      were soaked in India ink and sealed for 96 h. The teeth were cleared, and leakage
      was measured under stereoscopy. The Kruskal-Wallis test was used for analysis. A
      significant difference was found between EndoRez and RoekoSeal groups (P < 0.05).
      EndoRez had lower leakage values than RoekoSeal after 45-day exposure to the oral
      environment. No statistic difference was found in the comparison of AH Plus with
      the other sealers under study.

PMID- 18076579
TI  - Contemporary management of lateral root perforation diagnosed with the aid of
      dental computed tomography.
AB  - Lateral root perforation unnoticed during post-space preparation, and followed by
      post cementation, can subsequently be challenging to diagnose in the labio
      lingual plane due to the two-dimensional nature of conventional radiography. This
      paper demonstrates the application of a recently developed three-dimensional
      imaging system, cone beam computed tomography, in the diagnosis of iatrogenic
      root perforation. A clinical case is reported where labial post perforation in a
      maxillary central incisor occurring 15 years previously presented with a sinus
      tract and radiolucent lesion. Non-surgical retreatment and perforation repair
      using mineral trioxide aggregate was performed with the aid of an operating
      microscope. The sinus tract resolved with radiographic evidence of healing at 1
      year recall.

PMID- 18076580
TI  - Flare-ups in endodontics and their relationship to various medicaments.
AB  - The purpose of this research is to investigate the frequency of endodontic flare
      ups using a visual analogue scale. Definitions of flare-ups vary widely as does
      their reported frequency. A flare-up was defined as an increase of 20 or more
      points on the visual analogue scale for a given tooth, within the periods of 4 h
      and 24 h after the initial treatment appointment. The data from a previous study
      were used to determine the incidence of flare-ups after using three modalities
      (Ledermix, calcium hydroxide and no medication) to manage patients presenting for
      relief of pain of endodontic origin. A statistical analysis showed that there
      were no significant differences in flare-up rates at both the 4-h and 24-h
      periods between the three modalities. Further research is required using the
      above definition of a flare-up and standardising treatment protocols.

PMID- 18076581
TI  - Conservative treatment of patients with periapical lesions associated with
      extraoral sinus tracts.
AB  - This paper describes the clinical courses of three cases with extra-oral sinus
      tract formation, from diagnosis and treatment to short-term follow-up and
      evaluation. All teeth involved had periradicular radiolucent areas noted on
      radiographic examination and extra-oral sinus tracts appearing on the chin with
      exudation and unpleasant aesthetic appearance. The adopted treatment protocol
      included treating the sinus tract surface simultaneously with the root canal
      therapy. After root canal shaping using 5.25% sodium hypochlorite solution,
      calcium hydroxide-based pastes associated with different vehicles were inserted
      into the root canal for 4 months, and were changed monthly. All the sinus tracts
      healed in 7 to 10 days. The apical lesions were completely repaired in a maximum
      period of 24 months. The treatment adopted provided a complete healing of the
      periapical lesions in a short follow-up period. Surgical repair of the cutaneous
      sinus tract was therefore unnecessary.

PMID- 18076582
TI  - Healing of large periapical lesion: a non-surgical endodontic treatment approach.
AB  - A patient with a large periapical lesion around the apices of her mandibular
      incisors is presented. During the conservative non-surgical endodontic treatment,
      sodium hypochlorite was used for irrigation, and calcium hydroxide was used for
      the intra-canal dressing. Periapical healing was observed 1 month after
      obturation and continued in the 12-month recall. This report confirms that the
      large size of a periapical lesion does not mandate its surgical removal, and that
      even cyst-like periapical lesions heal following a conservative endodontic
      therapy.

PMID- 18076584
TI  - Dental Instrument Sterilization and Creutzfeldt-Jakob Disease.

PMID- 18076588
TI  - Novel, single-dose, topical treatment of tinea pedis using terbinafine: results
      of a dose-finding clinical trial.
AB  - Tinea pedis is the most common dermatophytosis requiring topical antifungals for
      at least 1-4 weeks. To determine the effectiveness of a novel topical single dose
      formulation of terbinafine (film forming solution-FFS) in the treatment of tinea
      pedis, 344 outpatients from 43 dermatological centres in France and Bulgaria
      suffering from tinea pedis with possible extension to soles confirmed by
      mycological examination (direct and culture) were evaluated for efficacy of
      terbinafine 1%, 5%, 10% FFS in a randomised double blind vehicle controlled
      parallel group dose finding study. Evaluations were carried out at baseline, 1
      and 6 weeks after a single application of FFS. Effective treatment rate based on
      negative mycology (direct and culture) and minimal signs and symptoms (two or
      less with only mild recorded) was measured at week 6. Effective treatment rates
      at week 6 with terbinafine 1%, 5% and 10% FFS were 66%, 70%, 61% compared with
      18% with placebo. All three active preparations were shown to be significantly
      superior to placebo (P < 0.001). Terbinafine 1% and 5% FFS were shown to be non
      inferior to terbinafine 10% FFS. Terbinafine 1% FFS is an effective, safe dose
      for the treatment of tinea pedis. This novel product represents a significant
      advance with the enhanced compliance and convenience that it offers.

PMID- 18076589
TI  - Usefulness and pharmacokinetic study of oral terbinafine for hyperkeratotic type
      tinea pedis.
AB  - To study and establish an optimal administration method of oral antifungal,
      terbinafine (TBF), for hyperkeratotic type tinea pedis, from the pharmacokinetic
      point of view, 20 patients with hyperkeratotic type tinea pedis were given TBF
      125 mg once daily for 4 weeks and observed over time for improvement in
      dermatological symptoms and mycological efficacy. Targeting five of the patients,
      TBF concentration in the stratum corneum was measured using the liquid
      chromatography/tandem mass spectrometry (LC-MS/MS) method. TBF was detected in
      the stratum corneum of the sole 1 week after beginning the treatment in some
      cases and reached its peak 1 week after the completion of the treatment with a
      concentration of 247.8 ng g(-1), which was approximately more than 50 times
      higher than its minimal inhibitory concentration against dermatophytes. TBF was
      not detected at 8 weeks post-treatment, although its concentration was 50.73 ng
      g(-1) at 6 weeks post-treatment. Its effectiveness rate (effective + markedly
      effective) was 95% (19/20) with no adverse reactions, including abnormal changes
      in the laboratory test values, in any patient. These results suggest that TBF is
      a useful drug to treat hyperkeratotic tinea pedis from the pharmacokinetic point
      of view.

PMID- 18076590
TI  - Naildex: pilot evaluation of an onychodystrophy severity instrument.
AB  - A valid and reliable measure that captures onychodystrophy disease severity is
      important for both clinical and research applications. Three hundred and twenty
      two patients at two Veterans Affairs Medical Centers with clinical evidence of
      onychodystrophy suggesting onychomycosis (at least 25% in a distal subungual
      pattern) were examined using Naildex parameters. Naildex scores were calculated
      by a combination of: per cent of each nail infected, area of each nail and number
      of infected nails. Patients also completed a nail-specific quality of life
      questionnaire (NailQoL) and nail samples were collected and examined
      mycologically. Data was analysed for all enrolled patients (n = 322) and patients
      with mycologically-confirmed onychomycosis (n = 243). Inter-rater reliability was
      calculated from two examiners who each evaluated 17 patients with mycologically
      confirmed onychomycosis. Significant correlations (P < 0.01) between Naildex and
      NailQoL as well as proxy measures (duration of infection) indicated construct
      validity of the instrument for all patients as well as mycologically-confirmed
      cases. Strong correlation (r = 0.754, P < 0.01, n = 17) indicated high inter-rate
      reliability. This pilot evaluation suggests that Naildex is a valid and reliable
      measure of onychomycosis severity.

PMID- 18076591
TI  - An ex-vivo oral mucosa infection model for the evaluation of the topical activity
      of antifungal agents.
AB  - Although Nystatin has been used since 1950s as a non-absorbable antifungal agent,
      there is still no reliable in-vivo data available stating a dose-effect
      relationship of Nystatin-suspension in the treatment of oropharyngeal infection
      with Candida albicans. Here, we studied the efficacy of a commercially available
      topical Nystatin suspension in a new ex-vivo model of candidiasis using porcine
      oral mucosa. After 48 and 96 h of C. albicans infection, 230 IU Nystatin
      (standard dosage), 100 IU and 20 IU proved to be equally efficacious. Multiple
      applications of Nystatin were not superior compared with single application. In
      dosages of 10 and 0.1 IU the activity of Nystatin suspension against C. albicans
      was no longer confirmed. In an agar diffusion model, the minimal biocidal
      concentration of Nystatin proved to be 0.25 IU. Our results suggest that the
      proposed porcine ex-vivo model is much closer to the in-vivo situation compared
      with other established in-vitro models of the treatment of muco-cutaneous
      candidiasis and may provide a substitute for animal models in the investigation
      of antifungal agents. Additionally, it seems to be a valuable tool for further
      investigations of the pathogenesis of C. albicans infections.

PMID- 18076592
TI  - Potent anti-microbial activity of traditional Chinese medicine herbs against
      Candida species.
AB  - Anti-candidial activities of eight traditional Chinese medicinal (TCM) herbs were
      evaluated against six different Candida species. TCM preparations were screened
      for antifungal activity using a standard agar diffusion assay. Following
      identification of potential candidate herbs, their minimum inhibitory
      concentration (MIC) values were determined using the standardised NCCLS M-27A
      broth microdilution assay. Among TCM herbs, Rhizoma Coptidis had potent
      antifungal activity against Candida glabrata, Candida krusei and Candida
      tropicalis, but not against Candida albicans, Candida dubliniensis and Candida
      parapsolosis. The MIC values of the Rhizoma Coptidis against C. glabrata, C.
      krusei and C. tropicalis were 50, 50 and 100 microg ml(-1) respectively. We
      report here, for the first time, the potent antifungal activity of Rhizoma
      Coptidis and Cortex phellodendri Chinesis on three different non-albicans Candida
      species, C. glabrata, C. krusei and C. tropicalis and hence their possible use as
      therapeutic agents.

PMID- 18076593
TI  - Study on the effect of neem (Azadirachta indica A. juss) leaf extract on the
      growth of Aspergillus parasiticus and production of aflatoxin by it at different
      incubation times.
AB  - Aflatoxins are secondary metabolites that are produced by toxigenic strains of
      some Aspergillus species on foods. Neem plant is a known inhibitor of aflatoxin
      production. We studied the effects of different concentrations of aqueous neem
      leaf extract on fungal growth and aflatoxin production by Aspergillus parasiticus
      (NRRL 2999) at different incubation times. The toxigenic fungus was cultured on
      sucrose low salts medium in the presence of various concentrations of extracts
      (0.2, 0.8, 3.12, 12.5 and 50% v/v). After shaking incubation of cultures for 2,
      4, 6, 8, 10 and 12 days at 28 degrees C, the fungal mycelia was collected and
      processed for determination of dry weight. Mycelia and culture media were assayed
      by TLC method to detect aflatoxin B(1) (AFB(1)). The extracts did not have any
      obvious effect on fungal growth. AFB(1) production in the control samples
      increased to the maximum level on the 8th day. The inhibition of aflatoxin
      synthesis by plant extracts was found to be time- and dose-dependent. The maximum
      inhibitory effect was 80-90% in the presence of 50% concentration that when
      compared with control samples was significant (P < 0.05). AFB(1)
      secretion/production ratio in all of control and treated samples, other than 2nd
      day, approximately stayed and neem had no effect on it.

PMID- 18076594
TI  - Molecular epidemiology of Candida species isolated from clinical specimens of
      intensive care unit patients.
AB  - Epidemiological analysis of nosocomial Candida infections has gained importance
      due to an increase in these infections during the recent years. This study
      investigated the prevalence of clinical infections of Candida in anesthesiology
      intensive care unit patients, and ascertains the level of genetic diversity in
      the Candida species. A total of 70 Candida isolates, consisting of 42 Candida
      albicans, 16 Candida glabrata and 12 Candida tropicalis strains isolated from
      various clinical sites of infection of anesthesiology intensive care unit
      patients, were analysed. The susceptibility of the isolates against amphotericin
      B and fluconazole was determined by microdilution method according to Clinical
      and Laboratory Standards Institute M27-A2 standards. The strains were typed by
      random amplified polymorphic DNA (RAPD)-PCR using OPE-03, OPE-18, RP4-2 and AP50
      1 primers. In the patients with Candida infections, most isolates exhibited
      different RAPD patterns. Only three C. albicans pairs isolated within a short
      time period had the same RAPD pattern. Most of the Candida infections in the
      anesthesiology intensive care unit of our hospital seem to be caused by
      endogenous strains. Exogenous spread of C. albicans infections occurred less
      frequently.

PMID- 18076595
TI  - Fungal skin infections among prison inmates in Abakaliki, Nigeria.
AB  - Of 402 prison inmates screened for fungal skin lesions, 79 (19.7%) showed skin
      lesions, which proved mycologically positive by microscopy and culture.
      Dermatophytes were responsible for skin lesions in 61 (77.2%) of the inmates,
      while non-dermatophytes accounted for 18 (22.8%) of the lesions. The
      dermatophytes recovered were mostly anthropophilic and included Trichophyton
      rubrum 33 (41.8%); T. mentagrophytes var. interdigitale 3 (3.8%); T. tonsurans 3
      (3.8%); T. violaceum 2 (2.5%); Epidermophyton floccosum 10 (12.7%). A zoophilic
      dermatophyte, Microsporum canis, was recovered from 10 (12.7%) cases. The non
      dermatophytes were Candida albicans 15 (19%) and Candida spp. 3 (3.8%).
      Trichophyton rubrum was the most frequently recovered dermatophyte (41.8%) and
      caused infections in a variety of sites. The groin was the most common site of
      infection being infected in 50% of the cases by both the dermatophytes and non
      dermatophytes. Younger inmates (17-24 years) recorded the highest prevalence of
      infection (45.6%). Newer inmates (>2 years) were found to be more infected than
      older ones.

PMID- 18076596
TI  - The genetic epidemiology of tinea versicolor in China.
AB  - To study the clinical and epidemiological profile of Pityriasis versicolor (PV)
      and to determine the possible genetic model for PV in Chinese Han, we
      investigated 503 patients with PV who were recruited by a questionnaire method.
      Statistical analysis, heritability and complex segregation analysis were
      performed using EPI INFO 6.0, SPSS 10.0, the Falconer method and the SAGE-REGTL
      programs. In the total 503 PV patients, the mean age of onset was 22.85 +/- 10.36
      years. For male and female patients, the peak ages of initial onset were both 20
      29 years. A total of 106 (21.1%) patients were reported to have a positive family
      history of PV. The mean age of onset in males with positive family history was
      earlier than those with negative family history (t = 3.58, P < 0.01). Higher rate
      of recurrence and longer duration were seen in the patients with positive family
      history than those with negative family history. The heritability of PV in first
      , second- and third-degree relatives was 48.13%, 40.11% and 27.20% respectively.
      Based on the REGTL results, the best model was a polygenic additive model for PV.

PMID- 18076597
TI  - Prevalence of Candida on the tongue and intertriginous areas of psoriatic and
      atopic dermatitis patients.
AB  - Data in the literature regarding the prevalence of Candida in psoriatic and
      atopic dermatitis patients are controversial. We conducted a prospective study to
      determine the prevalence of Candida on the tongue, axillae and groin of psoriatic
      patients when compared with atopic dermatitis patients and normal controls.
      During the period 2003-2005, data were collected from 100 psoriatic patients, 100
      patients with atopic dermatitis and 100 normal controls. Fungal test specimens
      for Candida were collected from the axillae, groin and tongue of each patient.
      There was no increase in the prevalence of Candida in intertriginous area of
      either psoriatic or atopic dermatitis patients. However, the prevalence of
      Candida on the tongue was significantly higher in psoriatic patients (32%)
      compared with atopic dermatitis (18%) (P = 0.024) and higher, although not
      significantly, than in normal controls (21%) (P = 0.08). Our study did not reveal
      higher prevalence of Candida in the axillae and groin of either psoriatic or
      atopic dermatitis patients. There was a higher prevalence of Candida on the
      tongue of psoriatic patients. The Candida of the tongue was asymptomatic and did
      not correlate with age, gender, type of psoriasis or severity of the disease,
      therefore we conclude that this is clinically irrelevant.

PMID- 18076598
TI  - Otomycosis in western Nigeria.
AB  - Otomycosis is a recognized clinical entity in the tropical regions of the world.
      However, there is scanty information on this disease in some parts of Sub-Saharan
      Africa. The aim of this study was to determine the prevalence and pattern of
      etiological agents of otomycosis in western Nigeria. Medical records of patients
      with otomycosis seen in the Otorhinolaryngology Department of the University
      College Hospital, Ibadan from 1996-2005 were reviewed for all essential clinical
      data. Of the 5784 patients with ear diseases, 378 (6.54%) had otomycosis which
      consisted of 145 (38.36%) males and 233 (61.64%) females. Seventeen patients
      (4.50%) had recurrence within six months of treatment, 4 (1.06%) had poorly
      controlled plasma glucose. A significant number of our patients, 52 (13.76%), had
      prior topical aural antibiotic treatment following misdiagnosis. The predominant
      etiological agents in our series were Aspergillus niger (48.35%) and Aspergillus
      fumigatus (33.96%).

PMID- 18076599
TI  - Pimecrolimus induced tinea incognito masquerading as intertriginous psoriasis.
AB  - A 58-year-old, obese, male, army officer was presented with tinea incognito of
      the groin masking intertriginous psoriasis. According to his history, he had
      pruritic, symmetrical erythematous eruption of the groin of 2-month duration that
      he treated himself by using topical pimecrolimus 1%. This medication had been
      prescribed for his 8-year son's atopic dermatitis by the paediatrician. Direct
      examination with potassium hydroxide preparation showed fungal hyphae and
      Trichophyton rubrum was isolated in culture. This is the second case of topical
      pimecrolimus induced tinea incognito. We also review the cutaneous disorders that
      tinea incognito may mimic.

PMID- 18076600
TI  - Successful multimodal therapy of invasive pulmonary and central nervous system
      aspergillosis in a neutropenic surgical patient: case report and review of the
      literature.
AB  - Invasive aspergillosis predominantly occurs in patients with impaired host
      defence and is often resistant to different therapeutically strategies. However,
      mortality significantly increases if the central nervous system is affected. In
      this report, we describe a case of successful treatment of invasive aspergillosis
      with cerebral involvement. The treatment consists of a medication of voriconazole
      and lipid-associated amphotericin B as well as a stereotactic neurosurgical
      procedure to drain an intracranial abscess.

PMID- 18076601
TI  - Subcutaneous phaeohyphomycosis caused by Cladosporium sphaerospermum.

PMID- 18076602
TI  - Amphotericin B-induced cutaneous leucocytoclastic vasculitis: case report.
AB  - A 37-year-old female patient was diagnosed with ulcerative colitis 8 months ago
      and medical treatment with oral azathioprine, low-dose corticosteroids and 5-ASA
      was started. Following 3 months without any symptoms, the patient had total
      colectomy and ileostomy. After this period, liposomal amphotericin B (3 mg kg(-1)
      day(-1)) was given with the diagnosis of probable fungal infection. Palpable
      purpuric skin lesions on the anterior surface of both legs appeared on the 55th
      day of amphotericin B treatment. Histological examination of a skin biopsy was
      consistent with leucocytoclastic vasculitis. We present a case of cutaneous
      leucocytoclastic vasculitis in which amphotericin B might presumably be the
      aetiological factor.

PMID- 18076603
TI  - Allergic bronchopulmonary aspergillosis complicating chronic obstructive
      pulmonary disease.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a well recognised entity which
      complicates the course of 1-2% of patients with asthma and 2-15% of cystic
      fibrosis. Also, current criteria generally require the presence of asthma or
      cystic fibrosis for recognition of ABPA. The occurrence of ABPA in conditions
      other than cystic fibrosis or bronchial asthma is rare. Patients with chronic
      obstructive pulmonary disease (COPD) have mucus hypersecretion and impaired
      mucociliary clearance but are not reported to develop ABPA. Herein, we report a
      50-year-old male who presented with an exacerbation of COPD due to co-existent
      ABPA. To our knowledge, this is the first report of such an association. We also
      speculate on mechanisms of causality and impact of ABPA on disease progression in
      COPD.

PMID- 18076604
TI  - Chronic necrotizing pulmonary aspergillosis successfully diagnosed, treated, and
      followed by ultrathin bronchoscope.
AB  - We present a case of chronic necrotising pulmonary aspergillosis (CNPA)
      successfully diagnosed, treated and followed by ultrathin bronchoscope. A 68-year
      old man was admitted to the hospital because of a cough and low-grade fever. A
      chest computerized tomography (CT) showed cavitary infiltrates in the superior
      segment of the left upper lobe. Bronchoscopic examination was performed using a
      2.8-mm ultrathin bronchoscope, which could be inserted into the cavity lesion
      under direct vision. Biopsy specimens from a whitish intracavity lesion showed
      septate-branching hyphae and cultures of the cavital washing grew Aspergillus
      fumigatus. Using the ultrathin bronchoscope, we instilled amphotericin B into the
      cavity before oral itraconazole therapy. The patient showed clinical improvement
      with resolution of the cavitary infiltrates on CT findings. The whitish
      intracavity lesion had prominently disappeared after 18 months of therapy. An
      ultrathin bronchoscope is useful for treating and assessing cavity lesions as
      well as establishing a diagnosis for CNPA patients.

PMID- 18076605
TI  - Characteristics of Mohs practices in the United States: a recall survey of ACMS
      surgeons.
AB  - OBJECTIVE: The purpose of this study is to better characterize the typical Mohs
      practice in the United States and to generate data that may be useful in future
      practice models. METHODS: A survey was mailed in 2004 to all 599 members of the
      American College of Mohs Surgery with United States addresses listed in the 2003
      directory. RESULTS: Most respondents were part of a single speciality group, in a
      suburban or urban setting, performed between 501-1,000 cases per year, and had
      been in practice from 0-5 years. The vast majority of Mohs excisions are for
      basal cell cancers and squamous cell cancers, followed by melanoma. Primary
      closure is the most common method of repair, followed by the use of flaps. Only
      6% of cases were referred to other specialties for closure. Many surgeons augment
      their practice with non-Mohs cosmetic procedures. CONCLUSION: The characteristics
      of current Mohs surgery practices in the United States provides useful data for
      training programs, potential trainees, workforce issues, statistical modeling
      systems, and Mohs surgeons in the evaluation of their own practices.

PMID- 18076606
TI  - Does imiquimod histologically rejuvenate ultraviolet radiation-damaged skin?
AB  - BACKGROUND: Imiquimod (IMI) 5% is believed by some to result in an improved
      cosmetic appearance of chronically ultraviolet radiation (UV)-damaged skin.
      OBJECTIVE: The objective was to determine what histologic and immunohistologic
      changes were present in actinically damaged skin after treatment with IMI.
      METHODS AND MATERIALS: Pre- and posttherapy biopsies of 12 patients with
      histories of actinic keratoses were evaluated with routine histology and
      immunohistochemical stains including p53, p63, proliferating cell nuclear antigen
      (PCNA), c-kit, and Factor XIIIa. RESULTS: After IMI therapy there was less
      compact hyperkeratosis, a more uniform rete ridge pattern with a more ordered
      proliferation of the epidermis, and a decrease in sun-damaged melanocytes. The
      papillary dermis showed a more uniform cellularity, and there was increased
      cellularity within the area of solar elastosis. After therapy, staining for p53,
      p63, and PCNA was decreased within the epidermis; staining for c-kit was
      decreased but more uniform in the basal cell; and Factor XIIIa expression was
      increased within the papillary dermis with a more ordered pattern of staining.
      CONCLUSION: These morphologic and immunohistochemical patterns may explain some
      of the improvement in overall skin appearance after IMI therapy and may be
      related to the spectrum of signaling pathways induced by the imidazoquinolines.

PMID- 18076607
TI  - Hydrophilic polymers with potassium salt and microporous polysaccharides for use
      as hemostatic agents.
AB  - BACKGROUND: Postoperative bleeding can lead to complications such as hematoma,
      infection, dehiscence, and an unscheduled office visit. Topical hemostatic agents
      can be used to aid in hemostasis. OBJECTIVE: The objective is to familiarize
      physicians with topical hemostatic agents--hydrophilic polymers with potassium
      salts (Urgent QR powder) and microporous polysaccharide hemispheres (Bleed-X).
      METHODS: Two hemostatic agents, microporous polysaccharide hemospheres and
      hydrophilic polymers with potassium salt, are discussed. The literature is
      reviewed. RESULTS: Numerous types of hemostatic agents exist. Topical hemostatic
      agents are safe, cost-effective, and efficient. CONCLUSION: Microporous
      polysaccharide hemospheres and hydrophilic polymers with potassium salts can be
      an adjunct to hemostasis after cautery and ligation. Patients can apply
      hemostatic agents if they experience any bleeding leading to decreased office
      visits. Hemostatic agents used intraoperatively shorten bleeding time and enable
      the physician to use less cautery. Using hemostatic agents can lead to fewer
      hematomas, infections, and office visits.

PMID- 18076608
TI  - Margin involvement after the excision of melanoma in situ: the need for complete
      en face examination of the surgical margins.
AB  - BACKGROUND: The standard treatment for cutaneous melanoma in situ is surgical
      excision followed by standard pathologic evaluation. Serial cross-sectioning
      (bread-loafing) may result in false negative margin examination and higher local
      recurrence rates than Mohs micrographic surgery, which histologically evaluates
      the entire surgical margin. OBJECTIVE: To estimate the sensitivity of bread
      loafing in detecting residual melanoma in situ at surgical margins. METHODS: A
      retrospective study was performed including 36 cases of melanoma in situ treated
      with Mohs surgery with positive margins after initial excision with 5 mm margins.
      The length of the margin involved with melanoma was measured. The ability of
      bread-loafing to detect residual tumor was calculated. RESULTS: The average
      linear extent of tumor at the surgical margin was 1.4 mm. Bread-loafing at 1, 2,
      4, and 10 mm intervals would have a 58, 37, 19, and 7% chance of detecting
      positive margins, respectively. In order to detect 100% of positive margins,
      bread-loafing would have to be performed every 0.1 mm. CONCLUSION: Bread-loaf
      cross-sections through excised melanoma specimens are inherently unreliable for
      detecting residual melanoma at the surgical margins. We recommend complete
      histologic margin control of the entire surgical margin using en-face tissue
      orientation (Mohs technique) to reduce the risk of recurrence.

PMID- 18076609
TI  - Reverse-flow retroauricular island flap in facial reconstruction.
AB  - BACKGROUND: Reconstruction of facial skin defects requires good-quality skin
      cover to satisfy aesthetic expectations of patient, especially when the skin
      defect is on the uncovered area of the face. Limitations in the available local
      tissue and donor-site morbidity restrict the options. OBJECTIVE: In an effort to
      solve these problems, we have begun to use a subcutaneous pedicled retroauricular
      reverse-flow flap. METHODS: Between January 1997 and December 2005, reverse-flow
      subcutaneous pedicled retroauricular island flap was used to cover facial defects
      in 12 patients who underwent surgical excision of skin tumor. The patients ranged
      in age from 44 to 81 years with a mean age of 58 years. RESULTS: Only one case
      experienced a superficial necrosis in the distal one-quarter part of the flap.
      The functional and aesthetic results were satisfactory for both patients and
      surgeons, and no tumor recurrence was observed during the 12 to 28 months (mean,
      18.8 months) follow-up period. CONCLUSIONS: This flap can be used reliably for
      the reconstruction of facial skin defects of small and medium size. The
      preference of frontal branch pedicled flap enables more distal facial area
      defects to be covered, such as dorsal nasal, nasolabial, and upper lip, than
      flaps based on parietal branch.

PMID- 18076610
TI  - Evaluation of the sclerotherapeutic efficacy of ethanol, polidocanol, and OK-432
      using an in vitro model.
AB  - BACKGROUND: Sclerosants are used to treat vascular malformations. Owing to
      variations in the flow, the injected concentrations and the duration of exposure
      of these sclerosants are altered. Therefore, the clinical effectiveness of
      sclerotherapy is variable. OBJECTIVE: The objective was to evaluate the
      differences in clinical response, usually observed among ethanol, polidocanol,
      and OK-432, using an in vitro sclerotherapy model. METHODS: Endothelial cells
      were cultured and exposed to different concentrations of the sclerosants for 5
      seconds and the remaining viable cells were counted using a MTT assay kit. Dyes
      were used to visualize the morphologic changes. Precipitant formation in blood
      was also evaluated. Finally, the degree of ICAM-1 expression, after exposure to
      lower concentrations of these sclerosants, was studied using immunocytochemistry.
      RESULTS: Only ethanol causes precipitant formation and kills almost all cells
      from 30% concentration. Polidocanol begins to disrupt the cell membrane from
      0.0125% onward. Only OK-432 induces ICAM-1 expression. CONCLUSION: Ethanol's
      strong precipitant-forming effect may induce thromboembolism, thus enhancing
      sclerosis. Polidocanol's endothelial cell-lysing effect was clearly documented.
      OK-432 may mediate its effect by inducing inflammatory response of the
      endothelium via ICAM-1 expression. This in vitro model may be useful in
      evaluating other sclerosants as well.

PMID- 18076611
TI  - The influence of 3% hydrogen peroxide on the survival rate of hair grafts when
      used as an antiseptic solution for surgical wound care: experience with five
      patients.
AB  - BACKGROUND: A solution of 3% hydrogen peroxide is one of the most widely used
      antiseptics to decrease bacterial colonization. OBJECTIVE: We performed this
      study to evaluate influence of 3% hydrogen peroxide on the survival rate of hair
      grafts. METHODS: We designed two templates on both frontoparietal recesses of
      five patients with male pattern alopecia. Follicular units containing single
      hairs were obtained from occiput. We grafted approximately 50 follicular units on
      each template. The gauze with normal saline was applied on the left template and
      the gauze with 3% hydrogen peroxide on the right template for 5 minutes. This
      procedure was repeated four times at 30-minute intervals. The number of surviving
      hairs of each template was counted 3 and 10 months after hair transplantation.
      RESULTS: There was no statistically significant difference in the mean survival
      rate of the grafts between hydrogen peroxide and normal saline 3 and 10 months
      after transplantation (Mann-Whitney test, p>.05). CONCLUSION: We think surgical
      wound care with 3% hydrogen peroxide during hair restoration surgery does not
      affect the survival rate of hair grafts when compared with normal saline. We also
      need further evaluation with larger participants to overcome small sample size
      and to gather other information.

PMID- 18076612
TI  - Use of a novel pulse dye laser for rapid single-pass purpura-free treatment of
      telangiectases.
AB  - BACKGROUND: Purpura-free elimination of telangiectases with a single pass of a
      pulsed dye laser with a large spot has proved difficult. OBJECTIVE: The purpose
      of this report was to define parameters that achieve single-pass purpura-free
      telangiectasia reduction. MATERIALS: Thirty patients between the ages of 23 and
      78 years were treated with a pulsed dye laser with a 10-mm spot and fluences
      ranging from 9 to 10 J/cm2. The macropulse width was 20 ms. Each macropulse was
      composed of eight pulselets. Treatments were carried out over facial areas with
      discrete telangiectases. RESULTS: Smaller telangiectases (<600 microm) showed
      transient bluing followed by stenosis. Larger vessels (600-10,000 microm) showed
      bluing but inconsistent closure. A second pass typically resulted in closure.
      CONCLUSION: A modified pulsed dye laser was capable of single-pass purpura-free
      reduction with a 10-mm spot size.

PMID- 18076613
TI  - Nonablative 1,064-nm Nd:YAG laser for treating atrophic facial acne scars:
      histologic and clinical analysis.
AB  - BACKGROUND: Non-ablative methods have been attempted in treating atrophic facial
      scars, but the histologic findings do not always coincide with the clinical
      results and patient satisfaction. OBJECTIVE: To study the effects and safety of
      the Nd:YAG laser for treating atrophic facial scars. MATERIAL AND METHODS: Twelve
      subjects (skin phototypes II-V) with mild to moderate atrophic facial acne scars
      received five monthly treatments with 1,064 nm Nd:YAG laser and were photographed
      before, in the middle of, and 6 months after the last treatment. Histologic
      evaluations were performed on skin biopsies obtained before treatment and 1 month
      after the last session. Collagen quantification per area, before and after the
      treatment, was performed by morphometry, with computerized image analysis.
      Patient satisfaction and clinical condition were assessed using standard grading
      scales. RESULTS: Mild to moderate clinical improvement was observed in most
      patients. Photographic assessment of scars found visible cosmetic improvement in
      eleven patients. All patients were satisfied. There were statistically
      significant collagen increases in the dermis following the treatment. Side
      effects were limited to mild transient erythema and increased skin sensitivity
      after the procedure. CONCLUSIONS: The 1,064 nm Nd:YAG laser is a safe and
      effective nonablative method for improving atrophic scars, even in darker skin.

PMID- 18076614
TI  - Use of a long-pulse alexandrite laser in the treatment of superficial pigmented
      lesions.
AB  - BACKGROUND/OBJECTIVE: Although the alexandrite 755-nm-wavelength laser is
      effective in the treatment of unwanted hair, there are no published studies
      gauging the efficacy of the variable long-pulse alexandrite laser in the
      treatment of superficial pigmented lesions. STUDY DESIGN/METHODS: Eighteen
      patients underwent a single treatment session using a variable pulse-width
      alexandrite laser. Test sites were performed using a 10-mm spot size and up to
      four pulse widths (3, 20, 40, 60 ms) with and without epidermal cooling. Full
      treatments were performed 3 weeks later using optimum test parameters. The
      patients were evaluated at 3 and 6 weeks. RESULTS: Patients with darker
      lentigines had greater lesion clearance than those patients with lighter colored
      lentigines. Shorter pulse widths and treatment without cryogen cooling both,
      independently, lowered the fluence threshold for lentigo clearance. CONCLUSION: A
      long-pulse alexandrite laser is effective in clearing solar lentigines in a
      single pass with minimal adverse effects.

PMID- 18076615
TI  - 308-nm excimer laser for the treatment of alopecia areata.
AB  - BACKGROUND: Alopecia areata is loss of hair from localized or diffuse areas of
      hair-bearing area of the skin. Recently there are reports of efficacy of the 308
      nm excimer radiation for this condition. OBJECTIVE: To study the effect of the
      308-nm excimer laser in the treatment of alopecia areata. MATERIALS AND METHODS:
      Eighteen patients with 42 recalcitrant patches (including 1 adult with alopecia
      totalis) were enrolled in this study. The lesions were treated with the 308-nm
      excimer laser twice a week for a period of 12 weeks; one lesion on each patient
      was left as a control for comparison. RESULTS: There were 7 males and 11 females
      in this study. Regrowth of hair was observed in 17 (41.5%) patches. Thirteen of
      the 18 lesions in scalp showed a complete regrowth of hair. The extremity regions
      failed to show a response. Atopic diatheses had an unfavorable effect on the
      outcome in our patients. CONCLUSION: The 308-nm excimer laser is an effective
      therapeutic option for patchy alopecia areata of the scalp and for some cases
      with patchy alopecia areata of the beard area. It does not work for patchy
      alopecia areata of the extremities.

PMID- 18076617
TI  - The natural history of untreated squamous cell carcinoma.

PMID- 18076616
TI  - Decision factors and the recognition of medical specialty in patients receiving
      cosmetic laser and intense pulsed light treatment.
AB  - BACKGROUND: In addition to dermatologists and plastic surgeons, physicians of
      other medical specialties also provide cosmetic laser and light treatment.
      OBJECTIVE: This study aimed to determine the major decision factors in patients
      who received cosmetic laser or intense pulsed light treatment and how they
      perceived different medical specialties in providing such services. METHODS: The
      method of factor analysis was adopted to extract the common characteristics
      (major decision factors) from a list of 17 items patients would regard as
      important when they planned to receive laser and intense pulsed light treatment.
      In addition, the level of recognition of different medical specialties in
      cosmetic patients was indirectly forecast using an analytic hierarchy process.
      RESULTS: Medical competence (0.3296) was the most important decision factor,
      followed by recommendation (0.2198), friendliness (0.1350), cost (0.1307),
      complete service (0.0984), and the physical attributes of the physician (0.0865).
      Dermatologists and plastic surgeons outscored cosmetic practitioners in five
      factors except for cost, in which the plastic surgeons were weakest. CONCLUSION:
      Medical competence and recommendation are the core issues for cosmetic patients.
      Dermatologists and plastic surgeons gain better overall recognition than
      physicians of other medical specialties in cosmetic patients.

PMID- 18076618
TI  - Tunneled transposition flap for reconstruction of defects of the nasal ala.

PMID- 18076619
TI  - Repair of vermilion Mohs defect with unilateral axial myocutaneous advancement
      flap.

PMID- 18076620
TI  - The combination nasal transposition flap and melolabial flap in reconstruction of
      difficult nasal defects.

PMID- 18076621
TI  - Localized cutis laxa and blepharoplasty.

PMID- 18076622
TI  - Lack of effect of the pulsed-dye laser in the treatment of multiple eccrine
      hidrocystomas: a report of two cases.

PMID- 18076623
TI  - Residual basal cell carcinoma after treatment with imiquimod: a caution on
      assuming complete cure.

PMID- 18076624
TI  - Chordoma cutis.

PMID- 18076625
TI  - Epidermodysplasia verruciformis in two brothers developing aggressive squamous
      cell carcinoma.

PMID- 18076626
TI  - Subcutaneous island pedicle flap with Z-plasty: a cosmetic enhancement.

PMID- 18076627
TI  - Re: Surface hinge flaps.

PMID- 18076628
TI  - Where was that biopsy taken?

PMID- 18076629
TI  - Use of insulin syringe for chemical cauterization.

PMID- 18076630
TI  - Chemical reconstruction of skin scars (CROSS) method using a syringe technique.

PMID- 18076632
TI  - Harnessing negative T-cell costimulatory pathways to promote engraftment.

PMID- 18076633
TI  - Overexpression of program death-1 in T cells has mild impact on allograft
      survival.
AB  - Program death-1 (PD-1), an inhibitory receptor upregulated on T cells upon TCR
      stimulation, has been shown to attenuate a number of immune responses in vivo,
      including acute allograft rejection. We tested whether constitutive expression of
      PD-1 would further inhibit allograft rejection. To this end, we generated
      transgenic mice expressing T-cell-restricted PD-1 under the control of the Lck
      proximal promoter and CD2 locus control. PD-1 transgenic (PD-1-Tg) mice did not
      develop gross abnormalities of thymic development and displayed normal numbers of
      thymocyte subsets and peripheral T cells. In vitro, PD-1-Tg T cells had reduced
      proliferative and cytokine secretion capacity upon TCR stimulation and cross
      linking of PD-1 resulted in diminished phosphorylation of protein kinase C-theta
      and Akt, as well as increased activation of the phosphate and tensin homolog.
      However, only T-cell responses to minor but not major mismatches were reduced in
      vitro. Similarly, PD-1-Tg mice exhibited prolonged survival of cardiac allografts
      only in mice transplanted with heart allografts expressing multiple minor
      mismatches and treated with suboptimal doses of cyclosporine A. We conclude that
      genetic engineering of T cells to express PD-1 constitutively has only a mild
      impact on allograft survival.

PMID- 18076634
TI  - Antibody to the Chlamydia trachomatis 60 kDa heat shock protein in follicular
      fluid and in vitro fertilization outcome.
AB  - PROBLEM: The association between 60 kDa Chlamydia trachomatis heat shock protein
      (CHSP60) antibodies and the etiology and outcomes of in vitro fertilization (IVF)
      outcomes is not well known. METHOD OF STUDY: A retrospective study with a double
      blind analysis of follicular fluid from 253 IVF patients for IgG antibodies to
      CHSP60. RESULTS: The CHSP60 antibodies were detected in 74.1% of women without
      embryo implantation and in 47.9% of women with 1-3 implantations per IVF cycle (P
      = 0.0004). CHSP60 antibodies were detected in 69.5% of women with tubal occlusion
      and 49.7% of women with other causes of infertility (P = 0.01). CHSP60 antibody
      detection was unrelated to maternal age, number of oocytes collected, or
      percentage of oocytes fertilized. CONCLUSION: Detection of IgG antibody to CHSP60
      may indicate persistence of C. trachomatis in the upper genital tract with low
      implantation rates resulting from a chronic inflammatory reaction. Alternatively,
      as human hsp60 is expressed in early stage embryogenesis, a cross-reacting
      antibody may induce destruction of the embryo.

PMID- 18076635
TI  - CD56+ cells are recruited to the uterus in two waves: at ovulation and during the
      first 2 weeks after missed menses.
AB  - PROBLEM: Uterine natural killer (uNK) cells are enriched in the post-ovulatory
      uterus and during pregnancy. Whether these cells arise from blood pre-cursors or
      from stem cells in the uterus is undefined. To support a hypothesis that
      precursors of uNK cells are recruited from blood, adhesive function of blood
      CD56+ subsets were assessed during one cycle and during pregnancy. METHOD OF
      STUDY: Fifteen women of proven fertility provided serial blood samples during one
      menstrual cycle and thirty women with a history of implantation failure or
      recurrent spontaneous abortion provided serial samples during infertility
      treatment. RESULTS: CD56(bright) cells, but not CD56(dim) cells or NKT cells,
      increased in ligand-binding capacity during ovulation in fertile cycles only and
      during the first 2 weeks from date of missed menses. CONCLUSION: Enhanced
      adhesive function at ovulation in CD56(bright) cells in fertile cycles and during
      early gestation supports a hypothesis of recruitment of pre-uNK cells from the
      blood CD56(bright) subset.

PMID- 18076636
TI  - RCAS1 decidual immunoreactivity and RCAS1 serum level during cesarean section
      with respect to the progression of labor.
AB  - PROBLEM: RCAS1 (a receptor-binding cancer antigen expressed on SiSo cells) is a
      membrane protein present also in a soluble form that seems to be responsible for
      the suppression of the cytotoxic immune response during gestation. The present
      study evaluates the decidual immunoreactivity level of RCAS1 and the serum level
      of RCAS1 with respect to the progression of labor at the time of cesarean
      section. METHOD OF STUDY: RCAS1 immunoreactivity was assessed by
      immunohistochemistry in 47 decidual samples, and the RCAS1 serum level was
      established in 47 blood serum samples derived from patients on whom cesarean
      sections were performed. The patients were divided into three groups according to
      the progression of their labor at the time when the cesarean was performed.
      RESULTS: The highest RCAS1 serum concentration and the highest RCAS1 decidual
      immunoreactivity were found in patients on whom cesarean sections were performed
      during advanced labor and were statistically, significantly higher than in cases
      where cesarean sections were performed without labor or after the spontaneous
      beginning of labor. CONCLUSION: Alterations in the RCAS1 serum and decidua levels
      seem to be associated with immune response changes during the progression of
      labor.

PMID- 18076637
TI  - Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G
      CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory
      and relapsed acute myeloid leukemia of the poor risk: a final report of the
      Polish Adult Leukemia Group.
AB  - OBJECTIVES: Patients with primary refractory AML and with early relapses have
      unfavorable prognoses and require innovative therapeutic approaches. Purine
      analogs fludarabine (FA) and cladribine (2-CdA) increase cytotoxic effect of Ara
      C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association
      with Ara-C and mitoxantrone (MIT) results in a synergistic effect. In the current
      report, we present the final results of multi-center phase II study evaluating
      the efficacy and toxicity of CLAG-M salvage regimen in poor risk
      refractory/relapsed AML patients. METHODS: The induction chemotherapy consisted
      of 2-CdA 5 mg/m2, Ara-C 2 g/m2, MIT 10 mg/m2, and granulocyte-colony stimulating
      factor. In the case of PR, a second CLAG-M was administered. Patients in CR
      received consolidation courses based on high doses of Ara-C and MIT with or
      without 2-CdA. RESULTS: One hundred and eighteen patients from 11 centers were
      registered; 78 primary resistant and 40 relapsed. Sixty-six patients (58%)
      achieved CR after one or two courses of CLAG-M, 49 (35%) were refractory, and 8
      (7%) died early. WBC >10 g/L and age >34 yr were factors associated with
      increased risk of treatment failure. Hematological toxicity was the most
      prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI
      4-23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both
      univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all
      66 patients in CR (95% CI 11-49%). Poor karyotype was the only factor associated
      with decreased probability of DFS. CONCLUSIONS: We conclude that CLAG-M is a well
      tolerated and highly effective salvage regimen in poor risk refractory/relapsed
      AML.

PMID- 18076638
TI  - Intravascular B-cell lymphoma with leukemic presentation: case report and
      literature review.
AB  - Intravascular lymphoma is an extremely rare, disseminated, and aggressive
      extranodal CD20+ non-Hodgkin's lymphoma characterized by the presence of lymphoma
      cells only in the lumina of small vessels. We report a 72-year-old woman with a
      diagnosis of intravascular lymphoma presented with splenomegaly and leukemic
      appearance in the peripheral blood smear. Her clinical course was rapidly
      deteriorated before the initiation of specific chemotherapy and finally died due
      to multiorgan insufficiency. Bone marrow biopsy revealed a characteristic
      infiltration of CD5, CD10 B-cell lymphoma. To our knowledge, this is the first
      reported case of a CD5, CD10 intravascular B-cell lymphoma with leukemic
      presentation in peripheral blood with multiple cytogenetic aberrations.

PMID- 18076639
TI  - Cytogenesis in the dentate gyrus after neonatal hyperthermia-induced seizures:
      what becomes of surviving cells?
AB  - PURPOSE: Febrile seizures (FS) are early-life seizures thought to play a role in
      epileptogenesis. By labeling cells that were dividing immediately following
      experimental FS, we previously demonstrated that significantly more of these
      newborn cells in the dentate gyrus (DG) survived 8 weeks later, relative to
      animals that did not experience FS. The purpose of the present study was to
      determine the long-term fate of these newborn cells. METHODS: On postnatal day
      (PN) 10, hyperthermia-induced seizures (HT, +/-42 degrees C core temperature)
      were evoked in Sprague-Dawley rats and littermates were used as normothermia
      controls (NT, +/-35 degrees C core temperature). From PN11 to PN16, rats were
      injected with bromodeoxyuridine (BrdU) to label dividing cells. At PN66, we
      evaluated the number of BrdU-labeled cells in the DG that colocalized with the
      neuronal marker NeuN, glial marker glial fibrillary acidic protein (GFAP),
      neuronal excitatory amino acid transporter 3 (EAAT3), GABAergic neuronal marker
      glutamic acid decarboxylase 67 (GAD67) or microglia marker tomato lectin (TL).
      RESULTS: In all rats, almost all BrdU-labeled cells in the DG, that showed double
      labeling, colocalized with NeuN, and rarely with GFAP, GAD67, or TL. In NT
      controls and HT rats that did not experience seizures ("HT-no seizures"),
      approximately 23% of BrdU-labeled cells colocalized with EAAT3, which was
      significantly different from 14% in HT rats that did experience seizures (HT +
      FS). DISCUSSION: Early-life seizures decrease the population of newborn cells
      that survive and mature into EAAT3-positive neurons and do not affect the
      GABAergic cell population. This may affect hippocampal physiology in young
      adulthood.

PMID- 18076640
TI  - A screening test for the prediction of Dravet syndrome before one year of age.
AB  - PURPOSE: Our aim was to develop a screening test to predict Dravet syndrome
      before the first birthday based on the clinical characteristics of infants and
      the SCN1A mutation analysis. METHODS: Ninety-six patients who experienced febrile
      seizures before the age of one were enrolled. The patients were divided into two
      groups-the Dravet syndrome group (n = 46) and the non-Dravet syndrome group (n =
      50). We compared the clinical characteristics before one year of age of the two
      groups. We analyzed all coding exons of the SCN1A gene by the direct sequencing
      method. Scores from 0 to 3 were assigned to each risk factor based on the odds
      ratio and p-value. RESULTS: An age of onset of febrile seizure <or= 7 months, a
      total number of seizures >or= 5, and prolonged seizures lasting more than 10 min.
      were regarded as significant risk factors for Dravet syndrome. Other factors
      highly predictive of this syndrome were hemiconvulsions, partial seizures,
      myoclonic seizures, and hot water-induced seizures. A total clinical score of six
      or above was the cutoff value indicating a high risk of Dravet syndrome. SCN1A
      missense and truncated mutations were detected significantly more often in the
      Dravet syndrome group than in the non-Dravet syndrome group. DISCUSSION: This
      simple screening test was designed to be used by general pediatricians. It could
      help to predict Dravet syndrome before one year of age. If the sum of the
      clinical risk score is >or= 6, then the performance of an SCN1A mutation analysis
      is recommended.

PMID- 18076641
TI  - Voxel-based analysis of whole brain FLAIR at 3T detects focal cortical dysplasia.
AB  - BACKGROUND: Focal Cortical Dysplasia (FCD) is an important cause for
      pharmacoresistant epilepsy that can be treated surgically. The identification of
      the abnormal cortex on standard MRI can be difficult and computational techniques
      have been developed to increase sensitivity. In this study we evaluate the
      potential of a novel whole-brain voxel-based technique using normalized FLAIR
      signal intensity (nFSI) at 3 Tesla. METHODS: Twenty-five patients with
      neuroradiologically reported FCD were included and compared to 25 healthy control
      subjects using Statistical Parametric Mapping (SPM5). T2 FLAIR scans were
      intensity normalized and each individual patient was compared against the control
      group. Each control subject was compared against the remaining control group.
      RESULTS: SPM correctly identified the FCD in 88% of cases (22/25) with only one
      false positive finding in the control group. In all but one of these cases the
      FCD was the most significant finding in the whole brain. All three missing cases
      could be detected at lower threshold levels but this would give rise to more
      false positive findings and thus reduce specificity. CONCLUSION: We present a
      novel technique that uses standard clinical T2 FLAIR scans to automatically
      detect FCDs. It can give supplementary information to the established T1-based
      automated techniques and could be useful for additional screening test, to
      complement the visual reading and clinical interpretation of MRI scans.

PMID- 18076642
TI  - Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during
      pregnancy in women with epilepsy.
AB  - OBJECTIVE: To further characterize pregnancy-induced alterations in the
      pharmacokinetics of lamotrigine (LTG). METHODS: Fifteen women treated with LTG
      were studied during 17 pregnancies. Complete trough blood samples from all
      trimesters and baseline > 1 month after delivery were available for 12
      pregnancies (Group A), whereas, five contributed with samples only from the third
      trimester and baseline (Group B). High-performance liquid chromatography (HPLC)
      was used to determine LTG plasma concentrations, and liquid chromatography-mass
      spectrometry to assay the main metabolite 2-N-lamotrigine glucuronide (2-N-GLUC)
      in plasma. RESULTS: In group A, the mean dose/plasma concentration ratio (D/C) of
      LTG at baseline after pregnancy was 66.5 +/- 17.9 (+/- SD) L/day and
      approximately 250% higher in late pregnancy. The mean lamotrigine-2-N
      glucuronide/lamotrigine plasma concentration ratio (2-N-GLUC/LTG) was 0.349 +/-
      0.141 (+/- SD) at baseline and 147% higher in late pregnancy. Taking group A and
      B together, the 2-N-GLUC/LTG ratio was 175% higher in the third trimester
      compared to baseline. CONCLUSION: Our study confirms a significant decline in LTG
      plasma levels during pregnancy in women on monotherapy with LTG. An increased 2-N
      GLUC/LTG ratio suggests that this decline may be related to an increased
      metabolism of LTG by glucuronidation.

PMID- 18076643
TI  - Possible role of the innate immunity in temporal lobe epilepsy.
AB  - PURPOSE: Temporal lobe epilepsy (TLE) is a multifactorial disease often involving
      the hippocampus. So far the etiology of the disease has remained elusive. In some
      pharmacoresistant TLE patients the hippocampus is surgically resected as
      treatment. To investigate the involvement of the immune system in human TLE, we
      performed large-scale gene expression profiling on this human hippocampal tissue.
      METHODS: Microarray analysis was performed on hippocampal specimen from TLE
      patients with and without hippocampal sclerosis and from autopsy controls (n = 4
      per group). We used a common reference pool design to perform an unbiased three
      way comparison between the two patient groups and the autopsy controls.
      Differentially expressed genes were statistically analyzed for significant
      overrepresentation of gene ontology (GO) classes. RESULTS: Three-way analysis
      identified 618 differentially expressed genes. GO analysis identified immunity
      and defense genes as most affected in TLE. Particularly, the chemokines CCL3 and
      CCL4 were highly (>10-fold) upregulated. Other highly affected gene classes
      include neuropeptides, chaperonins (protein protection), and the
      ubiquitin/proteasome system (protein degradation). DISCUSSION: The strong
      upregulation of CCL3 and CCL4 implicates these chemokines in the etiology and
      pathogenesis of TLE. These chemokines, which are mainly expressed by glia, may
      directly or indirectly affect neuronal excitability. Genes and gene clusters
      identified here may provide targets for developing new TLE therapies and
      candidates for genetic research.

PMID- 18076644
TI  - Feasibility of epilepsy follow-up care through telemedicine: a pilot study on the
      patient's perspective.
AB  - PURPOSE: Cost analysis and patient satisfaction with telemedicine in epilepsy
      care. METHODS: This controlled study included out-of-town epilepsy patients
      coming to follow-up at the University of Alberta hospital epilepsy clinic. After
      an informed consent, patients were randomized to either conventional (n = 18) or
      telemedicine (n = 23) clinics. Patients or caregivers filled patient satisfaction
      and travel cost questionnaires in both alternatives. Cost per visit analysis
      included costs of traveling, lodging, and lost productivity. RESULTS: Average age
      of the population was 41 years (range 19-73; 45% women). Eighty-three percent of
      patients preferred their next visit through telemedicine. About 90% of patients
      indicated a need for companion travel (mainly by car) to conventional clinic. For
      the conventional group patients the value of lost productivity was CAD $201,
      hotel cost CAD $8.50, and the value of car mileage CAD $256.50, totaling about
      CAD $466.00. Patient costs for telemedicine were CAD $35.85. Telemedicine
      production costs are similar to the patients' savings in traveling and lost
      productivity. About 90% of patients in both groups were satisfied with the
      quality of the service. CONCLUSION: Telemedicine can play a role in follow-up
      care of epilepsy patients, reduce patient costs, and improve patient
      satisfaction. This is the first full-time epilepsy telemedicine clinic in Western
      Canada.

PMID- 18076645
TI  - GABAA receptor-mediated activation of L-type calcium channels induces neuronal
      excitation in surgically resected human hypothalamic hamartomas.
AB  - PURPOSE: The human hypothalamic hamartoma (HH) is a rare, intrinsically
      epileptogenic lesion associated with gelastic seizures, but the underlying
      mechanisms remain unclear. Here, we examined the role of GABAA receptors in
      surgically resected HH tissue. METHODS: HH tissue slices (350 microm) were
      studied using cellular electrophysiological, calcium imaging, and
      immunocytochemical techniques. RESULTS: Two neuronal cell types were seen: small
      (10-16 microm) spontaneously firing GABAergic neurons and large (20-28 microm)
      quiescent neurons. In gramicidin-perforated patch recordings, muscimol (30
      microM) induced membrane depolarization in 70% of large (but not small) neurons
      and a concomitant rise in intracellular calcium. These responses were blocked by
      bicuculline methiodide (50 microM). Depolarizing neurons also exhibited more
      positive reversal potentials (Emuscimol) and significantly higher intracellular
      chloride concentrations compared to those that hyperpolarized. The cation
      chloride co-transporters NKCC1 and KCC2 were coexpressed in the majority of large
      neurons, but fluorometric measurements revealed that 84% of large HH neurons
      expressed solely or relatively more NKCC1. Bumetanide (20 microM), a NKCC1
      antagonist, partially suppressed muscimol-induced excitation in large neurons.
      Concordant with robust expression of CaV1.2 and CaV1.3 subunits in HH neurons,
      the L-type calcium channel blocker nifedipine (100 microM) prevented muscimol
      induced neuronal excitation. CONCLUSIONS: GABAA receptor-mediated excitation, due
      in part to differential expression of NKCC1 and KCC2 and subsequent activation of
      L-type calcium channels, may contribute to seizure genesis in HH tissue. Given
      the ready availability of L-type calcium channel blockers, our results have
      clinical ramifications for the treatment of seizures associated with HH lesions.

PMID- 18076646
TI  - Age-dependent cyclooxygenase-2 induction and neuronal damage after status
      epilepticus in the postnatal rat hippocampus.
AB  - PURPOSE: Epileptic seizures lead to age-dependent neuronal damage in the
      developing brain, particularly in the hippocampus, but the mechanisms involved
      have remained poorly elucidated. In this study, we investigated the contribution
      of apoptosis and inflammatory processes to neuronal damage after status
      epilepticus (SE) in postnatal rats. METHODS: SE was induced by an intraperitoneal
      injection of kainic acid (KA) in 21- and 9-day-old (P21 and P9) rats. The
      expression of Bax, Bcl-2 and caspase-3, markers for apoptosis, and cyclooxygenase
      2 (COX-2), an indicator for activation of inflammatory processes, were studied
      from 6 h up to 1 week after SE by Western blotting and immunocytochemistry.
      Neuronal damage was verified by Fluoro-Jade B staining. RESULTS: In P21 rats, SE
      resulted in neuronal damage in the CA1 neurons of the hippocampus. COX-2
      expression was extensively, but transiently, increased and its immunoreactivity
      pronouncedly enhanced in several hippocampal subregions, amygdala, and piriform
      cortex by 24 h after SE. The expression of Bax and caspase-3 remained unchanged,
      whereas the antiapoptotic factor Bcl-2 transiently decreased by 24 h. Single
      caspase-3 positive neurons appeared in the CA1 region of both control and KA
      treated rats. In P9 rats, no neuronal death was detected, and COX-2 expression
      and immunoreactivity remained at the control level. DISCUSSION: Our results
      suggest that SE provokes age-specific effects on COX-2 expression. This together
      with the activation of putative inflammatory processes may contribute to neuronal
      cell death in the hippocampus of postnatal rats, whereas caspase-dependent
      apoptosis seems not to be involved in the death process.

PMID- 18076647
TI  - Altered spatial distribution of PV-cortical cells and dysmorphic neurons in the
      somatosensory cortex of BCNU-treated rat model of cortical dysplasia.
AB  - PURPOSE: Cortical dysplasia (CD) represents a wide range of histopathological
      abnormalities of the cortical mantle that are frequently associated with drug
      resistant epilepsy. Recently, carmustine (1-3-bis-chloroethyl-nitrosurea [BCNU]),
      given to pregnant rats on embryonic day (E) 15, has been used to develop an
      experimental model mimicking human CD. The aim of this study was to characterize
      cytological and histological alterations in this model, and compare the results
      with those observed in human CD. METHODS: Pregnant rats were given
      intraperitoneal injections of BCNU on E15. Sections of cerebral cortex from adult
      BCNU-treated rats were cytoarchitecturally and immunohistochemically analyzed
      using anti-SMI311, anticalbindin (CB), and antiparvalbumin (PV) antibodies. The
      density of the PV-immunoreactive (PV-ir) interneurons was quantitatively assessed
      by means of a two-dimensional cell-counting technique, and the spatial
      distribution of PV-ir neurons was evaluated by using the Voronoi tessellation.
      RESULTS: The morphological features included reduced cortical size, laminar
      disorganization, and heterotopic clusters of neurons. We also identified large,
      disoriented SMI311-positive pyramidal neurons, and dysmorphic neurons intensely
      immunostained for neurofilaments, similar to those observed in human dysplastic
      cortex. An altered distribution of PV-immunoreactive cortical interneurons was
      also present. CONCLUSIONS: Although some of the cytoarchitectural abnormalities
      found in BCNU-exposed cortex are similar to those found in other CD models, we
      identified new alterations that recall the neuropathological description of type
      IIA (Taylor's type) CD. BCNU-treated rat could therefore be a useful additional
      model for investigating the pathogenic mechanisms involved in this CD.

PMID- 18076648
TI  - Analysis of the molecular dynamics of medaka nuage proteins by fluorescence
      correlation spectroscopy and fluorescence recovery after photobleaching.
AB  - The nuage is a unique organelle in animal germ cells that is known as an electron
      dense amorphous structure in the perinuclear region. Although the nuage is
      essential for primordial germ cell (PGC) determination and development, its roles
      and functions are poorly understood. Herein, we report an analysis of the
      diffusion properties of the olvas gene product of the medaka fish (Oryzias
      lapites) in PGCs prepared from embryos, using fluorescence correlation
      spectroscopy and fluorescence recovery after photobleaching. Olvas-green
      fluorescent protein (GFP) localized in granules thought to be nuages, and
      exhibited a constraint movement with two-component diffusion constants of 0.15
      and 0.01 microm(2).s(-1). On the other hand, cytosolic Olvas-GFP was also
      observed to have a diffusion movement of 7.0 microm(2).s(-1). Interestingly,
      Olvas-GFP could be expressed in HeLa cells, and formed granules that were similar
      to nuages in medaka PGCs. Olvas-GFP also exhibited a constraint movement in the
      granules and diffused in the cytosol of HeLa cells, just as in the medaka embryo.
      The other two gene products, Nanos and Tudor of the medaka, which are known as
      constituents of the nuage, could also be expressed in HeLa cells and formed
      granules that colocalized with Olvas-GFP. Nanos-GFP and Tudor-GFP exhibited
      constraint movement in the granules and diffused in the cytosol of HeLa cells.
      These results suggest that these granules in the HeLa cell are not simple
      aggregations or rigid complexes, but dynamic structures consisting of several
      proteins that shuttle back and forth between the cytosol and the granules.

PMID- 18076649
TI  - Helicobacter pylori neutrophil-activating protein activates neutrophils by its C
      terminal region even without dodecamer formation, which is a prerequisite for DNA
      protection--novel approaches against Helicobacter pylori inflammation.
AB  - Helicobacter pylori neutrophil-activating protein (HP-NAP) protects DNA from free
      radicals as a dodecamer through its ferroxidase activity without, however,
      directly binding to it. The retardation that was observed at pH 7.5 could be
      easily attributed to an iron effect, as it was revealed by experiments in the
      absence of HP-NAP. A total loss of ferroxidase activity, dodecamer formation and
      DNA protection in environments rich in free radicals was observed after
      replacement of His25, His37, Asp52 and Lys134, which are located within the
      ferroxidase site, with Ala. Molecular dynamics simulations revealed that dimer
      formation is highly unlikely following mutation of the above amino acids, as the
      Fe(2+) is no longer attracted with equal strength by both subunits. These
      findings probably indicate that iron plays an important role in the conformation
      of HP-NAP by initiating the formation of stable dimers that are indispensable for
      the ensuing dodecamer structure. Very surprisingly, neutrophil activation
      appeared to be stimulated by structural elements that are localized within the C
      terminal region of both mutant HP-NAP and wild-type dodecamer HP-NAP. In
      particular, the dodecamer conformation does not seem to be necessary for
      activation, and helices H3 (Leu69-Leu75) and H4 (Lys89-Leu114) or the linking
      coils (His63-Thr68 and Thr76-Ser88) are probably critical in stimulating
      neutrophil activation.

PMID- 18076650
TI  - Ubiquitin C-terminal hydrolase-L1 (Uch-L1) correlates with gonadal transformation
      in the rice field eel.
AB  - The ubiquitin-proteasome pathway is crucial for a variety of biological
      processes, including spermatogenesis. Ubiquitin C-terminal hydrolase-L1 (Uch-L1)
      is thought to associate with monoubiquitin to control ubiquitin levels. Here, we
      report the identification of Uch-L1 cDNA from the testis of the rice field eel, a
      natural sex reversal vertebrate, by using cDNA microarray analysis. Uch-L1
      encodes a protein of 220 amino acids that shows high homology to Uch-L1 of
      vertebrates, especially fish species. Both mRNA and protein are mainly expressed
      in testis, ovotestis and ovary, as well as in the brain. Immunohistochemistry
      analysis revealed differential expression of Uch-L1 in three kinds of gonads. In
      the ovary, expression of Uch-L1 was observed mainly in the developing ovary and
      slightly in the mature ovary. In ovotestis during the intersex stage, Uch-L1 was
      expressed in the male gonad epithelium and degraded ovary. In testis, expression
      was observed in developing germ cells, including spermatogonia and spermatocytes.
      Furthermore, Uch-L1 was upregulated during gonadal transformation, especially
      from the beginning of the intersex stage onwards. Native-PAGE showed that Uch-L1
      underwent dimerization and oligomerization in gonads, and that the relative level
      of dimerization/oligomerization decreased during gonadal transformation.
      Simultaneously, ubiquitin polypeptide expression was upregulated during this
      process. These results suggest that Uch-L1, via the ubiquitin-proteasome system,
      may play an important role not only in gametogenesis, but also in the gonadal
      transformation process in the rice field eel.

PMID- 18076651
TI  - Thermal unfolding mechanism of lipocalin-type prostaglandin D synthase.
AB  - Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is a dual-functioning
      protein in the lipocalin family, acting as a PGD(2)-synthesizing enzyme and as an
      extracellular transporter for small lipophilic molecules. We earlier reported
      that denaturant-induced unfolding of L-PGDS follows a four-state pathway,
      including an activity-enhanced state and an inactive intermediate state. In this
      study, we investigated the thermal unfolding mechanism of L-PGDS by using
      differential scanning calorimetry (DSC) and CD spectroscopy. DSC measurements
      revealed that the thermal unfolding of L-PGDS was a completely reversible process
      at pH 4.0. The DSC curves showed no concentration dependency, demonstrating that
      the thermal unfolding of L-PGDS involved neither intermolecular interaction nor
      aggregation. On the basis of a simple two-state unfolding mechanism, the ratio of
      van't Hoff enthalpy (DeltaH(vH)) to calorimetric enthalpy (DeltaH(cal)) was below
      1, indicating the presence of an intermediate state (I) between the native state
      (N) and unfolded state (U). Then, statistical thermodynamic analyses of a three
      state unfolding process were performed. The heat capacity curves fit well with a
      three-state process; and the estimated transition temperature (T(m)) and enthalpy
      change (DeltaH(cal)) of the N<-->I and I<-->U transitions were 48.2 degrees C and
      190 kJ.mol(-1), and 60.3 degrees C and 144 kJ.mol(-1), respectively.
      Correspondingly, the thermal unfolding monitored by CD spectroscopy at 200, 235
      and 290 nm revealed that L-PGDS unfolded through the intermediate state, where
      its main chain retained the characteristic beta-sheet structure without side
      chain interactions.

PMID- 18076652
TI  - The C-terminus of viral vascular endothelial growth factor-E partially blocks
      binding to VEGF receptor-1.
AB  - Vascular endothelial growth factor (VEGF) family members play important roles in
      embryonic development and angiogenesis during wound healing and in pathological
      conditions such as tumor formation. Parapoxviruses express a new member of the
      VEGF family which is a functional mitogen that specifically activates VEGF
      receptor (VEGFR)-2 but not VEGFR-1. In this study, we show that deletion from the
      viral VEGF of a unique C-terminal region increases both VEGFR-1 binding and VEGFR
      1-mediated monocyte migration. Enzymatic removal of O-linked glycosylation from
      the C-terminus also increased VEGFR-1 binding and migration of THP-1 monocytes
      indicating that both the C-terminal residues and O-linked sugars contribute to
      blocking viral VEGF binding to VEGFR-1. The data suggest that conservation of the
      C-terminal residues throughout the viral VEGF subfamily may represent a means of
      reducing the immunostimulatory activities associated with VEGFR-1 activation
      while maintaining the ability to induce angiogenesis via VEGFR-2.

PMID- 18076653
TI  - The Atlantic salmon Z-DNA binding protein kinase phosphorylates translation
      initiation factor 2 alpha and constitutes a unique orthologue to the mammalian
      dsRNA-activated protein kinase R.
AB  - The translation initiation factor 2 alpha (eIF2alpha)-kinase, dsRNA-activated
      protein kinase (PKR), constitutes one of the major antiviral proteins activated
      by viral infection of vertebrates. PKR is activated by viral double-stranded RNA
      and subsequently phosphorylates the alpha-subunit of translation initiation
      factor eIF2. This results in overall down regulation of protein synthesis in the
      cell and inhibition of viral replication. Fish appear to have a PKR-like protein
      that has Z-DNA binding domains instead of dsRNA binding domains in the regulatory
      domain, and has thus been termed Z-DNA binding protein kinase (PKZ). We present
      the cloning of the Atlantic salmon PKZ cDNA and show its upregulation by
      interferon in Atlantic salmon TO cells and poly inosinic poly cytodylic acid in
      head kidney. We also demonstrate that recombinant Atlantic salmon PKZ, expressed
      in Escherichia coli, phosphorylates eIF2alphain vitro. This is the first
      demonstration that PKZ is able to phosphorylate eIF2alpha. PKZ activity, as
      measured by phosphorylation of eIF2alpha, was increased after addition of Z-DNA,
      but not by dsRNA. In addition, we show that wild-type Atlantic salmon PKZ, but
      not the kinase defective variant K217R, has a direct inhibitory effect on protein
      synthesis after transient expression in Chinook salmon embryo cells. Overall, the
      results support a role for PKZ, like PKR, in host defense against virus
      infection.

PMID- 18076654
TI  - Mass spectrometric detection of tyrosine sulfation in human pancreatic
      trypsinogens, but not in tumor-associated trypsinogen.
AB  - Trypsinogen-1 and -2 are well-characterized enzymes that are expressed in the
      pancreas and also in several other tissues. Many cancers produce trypsinogen
      isoenzymes that differ from the pancreatic ones with respect to substrate
      specificity and isoelectric point. These tumor-associated trypsinogens play a
      pivotal role in cancer progression and metastasis. The differences between these
      and the pancreatic isoenzymes have been suggested to be caused by post
      translational modification, either sulfation or phosphorylation of a tyrosine
      residue. We aimed to elucidate the cause of these differences. We isolated
      trypsinogens from pancreatic juice and conditioned medium from a colon carcinoma
      cell line. Intact proteins, and tryptic and chymotryptic peptides were
      characterized by electrospray ionization mass spectrometry. We also used
      immunoblotting with antibody against phosphotyrosine and N-terminal sequencing.
      The results show that pancreatic trypsinogen-1 and -2 are sulfated at Tyr154,
      whereas tumor-associated trypsinogen-2 is not. Detachment of a labile sulfogroup
      could be demonstrated by both in-source dissociation and low-energy collision
      induced dissociation in a tandem mass spectrometer. Tyrosine sulfation is an
      ubiquitous protein modification occurring in the secretory pathway, but its
      significance is often underestimated due to difficulties in its analysis.
      Sulfation is an almost irreversible modification that is thought to regulate
      protein-protein interactions and the activity of proteolytic enzymes. We conclude
      that the previously known differences in charge, substrate specificity and
      inhibitor binding between pancreatic and tumor-associated trypsinogens are
      probably caused by sulfation of Tyr154 in pancreatic trypsinogens.

PMID- 18076655
TI  - Two novel Mesocestoides vogae fatty acid binding proteins--functional and
      evolutionary implications.
AB  - This work describes two new fatty acid binding proteins (FABPs) identified in the
      parasite platyhelminth Mesocestoides vogae (syn. corti). The corresponding
      polypeptide chains share 62% identical residues and overall 90% similarity
      according to CLUSTALX default conditions. Compared with Cestoda FABPs, these
      proteins share the highest similarity score with the Taenia solium protein. M.
      vogae FABPs are also phylogenetically related to the FABP3/FABP4 mammalian FABP
      subfamilies. The native proteins were purified by chromatographical procedures,
      and apparent molecular mass and isoelectric point were determined.
      Immunolocalization studies determined the localization of the expression of these
      proteins in the larval form of the parasite. The genomic exon-intron organization
      of both genes is also reported, and supports new insights on intron evolution.
      Consensus motifs involved in splicing were identified.

PMID- 18076656
TI  - Facets of lupus erythematosus: panniculitis responding to thalidomide.
AB  - Lupus erythematosus profundus or lupus panniculitis is a rare clinical variant of
      lupus erythematosus, which involves the deep dermis and subcutaneous fat.
      Diagnosis may be difficult in cases with isolated involvement. Further
      manifestations of lupus erythematosus may thus be essential for diagnosis, which
      depends on the clinical picture, histopathology and a positive lesional lupus
      band test. We report a severe, mutilating case of lupus panniculitis, which
      responded well to thalidomide.

PMID- 18076657
TI  - Bone mineral density and single photon emission computed tomography changes after
      total knee arthroplasty: a 2-year follow-up study.
AB  - Dual X-ray absorptionmetry (DXA) provides a highly reproducible method for
      quantitative analysis and monitoring periprosthetic bone mineral density (BMD)
      after total knee arthroplasty (TKA). Single photon emission computed tomography
      (SPECT) with bone avid radiopharmaceuticals reflects bone metabolic activity and
      circulation. We combined information from DXA and SPECT to assess the evaluation
      of the dynamic balance between BMD and bone turnover. Sixteen patients underwent
      serial DXA (Lunar Expert XL) and 99mTc-methylene diphosphonate SPECT measurements
      until 2 years after TKA. A rapid bone loss, up to 25.5%, was detected in femur
      during the first six postoperative months. However, tibial periprosthetic BMD
      remained close to baseline. There was a significant correlation between 12-month
      SPECT uptake and preceding BMD change in medial tibia (r = 0.5, P = 0.044). At 12
      months, SPECT uptakes in the operated knee were notably higher compared with
      those of the control knee. SPECT uptakes showed statistically significant
      decreases from 12 months to 24 months, while SPECT uptake in the control knee
      remained stable. In tibia, the results are more complex; referring that increased
      bone remodelling is continuing below the tibial tray. Furthermore, femoral
      diaphyseal uptake remained elevated, while corresponding tibial uptake had
      levelled off at 2 years. Increased SPECT uptake during the first 2 years after
      uncomplicated TKA results most likely from normal postoperative bone remodelling.
      Levelling of SPECT uptake may indicate a new balance between bone loss and
      regain.

PMID- 18076658
TI  - Effects of local alpha2-adrenergic receptor blockade on adipose tissue lipolysis
      during prolonged systemic adrenaline infusion in normal man.
AB  - During prolonged adrenaline infusion, lipolysis peaks within 30 min and
      thereafter tends to decline, and we hypothesized that the stimulation of local
      adipose tissue alpha2-adrenergic receptors accounts for this decline. The
      lipolytic effect of a prolonged intravenous adrenaline infusion combined with
      local infusion of the alpha2-blocker phentolamine in superficial and deep
      abdominal subcutaneous adipose tissue and in preperitoneal adipose tissue was
      studied in seven healthy subjects. The interstitial glycerol concentration in the
      three adipose tissue depots was measured by the microdialysis method. Regional
      adipose tissue blood flow was measured by the (133)Xe clearance technique.
      Regional glycerol output (lipolytic rate) was calculated from these measurements
      and simultaneous measurements of arterial glycerol concentrations. Adrenaline
      infusion increased lipolysis in all three depots (data previously published).
      Phentolamine infusion did not augment lipolysis in the subcutaneous depots while
      it increased the lipolytic rate in the preperitoneal depot. It is concluded that
      alpha2-adrenergic receptors do not have a significant effect on subcutaneous
      adipose tissue lipolysis during high circulating adrenaline concentrations, and
      the decrease in lipolysis in subcutaneous adipose tissue under prolonged
      adrenaline stimulation is thus not attributed to alpha2-adrenergic receptor
      inhibition of lipolysis. However, in the preperitoneal adipose tissue depot,
      alpha2-adrenergic receptor tone plays a role for the lipolytic rate obtained
      during prolonged adrenaline stimulation.

PMID- 18076659
TI  - Left ventricular end-diastolic geometrical adjustments during exercise in
      endurance athletes.
AB  - The increase in left ventricular (LV) end-diastolic volume has recently been
      shown to explain more than 70% of the increase in stroke volume during upright
      exercise in endurance athletes. As the end-diastolic volume enhancement not could
      be explained by an increase in axial cavity length an augmentation in LV short
      axis diameters is to be expected. To investigate LV end-diastolic geometrical
      alterations during exercise, 15 endurance athletes were examined using contrast
      exercise echocardiography. LV end-diastolic short-axis diameters were made from
      apical views at several LV cavity levels. From upright rest to upright exercise
      the LV end-diastolic internal cavity measurements increased significantly. During
      exercise, the LV cavity became geometrically more spherical with the largest
      increase in the LV end-diastolic short-axis cavity diameters in the mid and
      apical parts of the left ventricle. The LV internal long axis showed significant
      increase from rest to exercise but the absolute increase was small.

PMID- 18076660
TI  - Wegener's granulomatosis presenting as pyoderma gangrenosum.
AB  - Half of the patients with Wegener's granulomatosis develop skin lesions due to
      the systemic vasculitis. Wegener's granulomatosis should be included in the
      differential diagnostic considerations for necrotic ulcers, including leg ulcers.
      We present a case which demonstrates the importance of histological evaluation of
      a skin biopsy from the margin of the ulcer for establishing the diagnosis.
      Antineutrophil cytoplasmic antibodies with antigen specificity for proteinase 3
      (PR3-ANCA) were detected supporting the diagnosis of Wegener granulomatosis.
      Further evaluation showed involvement of the eyes and kidneys. The ulcer rapidly
      healed under treatment with cyclophosphamide and corticosteroids.

PMID- 18076661
TI  - Fixed drug eruption: state of the art.
AB  - Fixed drug eruption (FDE) is a common type of cutaneous adverse drug reaction.
      There may be a genetic background as significant associations have been
      identified between HLA types and specific FDE.Systemic provocation is still the
      gold standard for establishing the offending agent in FDE,but topical provocation
      testing offers a promising alternative approach. A standardized method does not
      exist, and the approach must likely be varied for different agents. The mystery
      of site preference in FDE is still unresolved. Possible explanations include
      properties of the drug, trauma and viscerocutaneous reflex patterns.

PMID- 18076662
TI  - Basal cell carcinoma of the nipple - an unusual location in a male patient.
AB  - Although basal cell carcinoma is extremely common, it only rarely occurs on the
      nipple. Men are affected more often than women. Basal cell carcinoma of the
      nipple-areola complex may be more aggressive as metastases to regional lymph
      nodes have been reported. We report a basal cell carcinoma of the nipple with
      features of a fibroepithelioma of Pinkus in a man and review the literature.

PMID- 18076663
TI  - Evaluation of the Vitek-2 extended-spectrum beta-lactamase test against non
      duplicate strains of Enterobacteriaceae producing a broad diversity of well
      characterised beta-lactamases.
AB  - The Vitek-2 extended-spectrum beta-lactamase (ESBL) test was assessed using a
      collection of 94 ESBL-positive and 71 ESBL-negative non-duplicate isolates of
      Enterobacteriaceae. These isolates produced a wide diversity of well
      characterised beta-lactamases, including 61 different ESBLs, two class A
      carbapenemases and various species-specific beta-lactamases. ESBL detection was
      performed using (i) the conventional synergy test as recommended by the Comite de
      l'Antibiogramme de la Societe Francaise de Microbiologie, (ii) the CLSI
      phenotypic confirmatory test for ESBLs, and (iii) the Vitek-2 ESBL test. For
      Escherichia coli and klebsiellae, the sensitivity/specificity values were
      97.3%/96.9% for the synergy test, 91.8%/100% for the CLSI phenotypic confirmatory
      test, and 91.8%/100% for the Vitek-2 ESBL test. For other organisms, the
      sensitivity/specificity values were 100%/97.4% for the synergy test, 90.5%/100%
      for the CLSI phenotypic confirmatory test, and 90.5%/100% for the Vitek-2 ESBL
      test. The Vitek-2 ESBL test seemed to be an efficient method for routine
      detection of ESBL-producing isolates of Enterobacteriaceae, including isolates
      producing AmpC-type enzymes.

PMID- 18076664
TI  - Long-term follow-up of patients with tuberculosis as a complication of tumour
      necrosis factor (TNF)-alpha antagonist therapy: safe re-initiation of TNF-alpha
      blockers after appropriate anti-tuberculous treatment.
AB  - This study investigated the long-term outcome of patients with tuberculosis (TB)
      as a complication of tumour necrosis factor (TNF)-alpha blocker therapy. All TB
      cases (n = 21) complicating TNF-alpha blocker therapy from French university
      hospitals were collated between January 2000 and September 2002. Outcome was
      assessed via a postal questionnaire during September 2005. The mortality rate
      after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had
      recommenced TNF-alpha antagonist treatment, after appropriate anti-TB therapy,
      without reactivation. These data support the concept that TNF-alpha antagonists
      can be restarted in TB patients provided that adequate anti-TB treatment has been
      completed.

PMID- 18076665
TI  - Use of a multiplex PCR-based reverse line blot (mPCR/RLB) hybridisation assay for
      the rapid identification of bacterial pathogens.
AB  - The aim of this study was to develop a sensitive and reliable method for the
      molecular identification of pathogenic bacteria. A multiplex PCR-based reverse
      line blot (mPCR/RLB) hybridisation assay was developed and evaluated for the
      rapid identification of 24 systemic and respiratory bacterial pathogens in
      routine diagnosis. All species-specific probes designed for the RLB hybridised
      with amplified DNA only from the corresponding species. Sensitivity limits of the
      mPCR/RLB assay varied among the 24 target organisms from 0.05 pg to 0.5 ng of
      genomic DNA. The sensitivity of the assay was 2 x 10(2) CFU/mL for Streptococcus
      pneumoniae and 6 x 10(2) CFU/mL for Escherichia coli. The specificity of each
      probe was tested against 24 species. There were no cross-reactions among any of
      the 43 probes. The mPCR/RLB assay appeared to be a useful alternative tool for
      the molecular identification of common pathogens.

PMID- 18076667
TI  - Quinolone resistance among Shigella spp. isolated from travellers returning from
      India.
AB  - Among 200 isolates of Shigella from patients with travellers' diarrhoea, 12
      isolates (four isolated in 1995-2000 and eight in 2001-2004) exhibited quinolone
      resistance. Nine of these isolates originated from India. These resistant
      isolates had at least one amino-acid substitution in GyrA. Quinolone resistance
      is increasing in Shigella spp. causing travellers' diarrhoea, and particularly
      among isolates causing diarrhoea in travellers returning from India.

PMID- 18076666
TI  - Identification of immunodominant VP1 linear epitope of enterovirus 71 (EV71)
      using synthetic peptides for detecting human anti-EV71 IgG antibodies in Western
      blots.
AB  - A major IgG-specific immunodominant VP1 linear epitope of enterovirus 71 (EV71)
      strain 41 (5865/SIN/00009), defined by the core sequence LEGTTNPNG, was
      identified by Pepscan analysis. Oligonucleotides corresponding to the amino-acid
      sequence of synthetic peptide SP32 were cloned and over-expressed in Escherichia
      coli as a recombinant glutathione-S-transferase (GST)-SP32 fusion protein. In
      ELISAs, this protein did not react with human anti-EV71 IgG antibodies, but there
      was significant immunoreactivity according to western blot analysis. The amino
      acid sequence of SP32 was highly specific for detecting EV71 strains in western
      blot analysis, and showed no immunoreactivity with monoclonal antibodies raised
      against other enteroviruses, e.g., CA9 and Echo 6.

PMID- 18076668
TI  - Investigation of promoter variations in dendritic cell-specific ICAM3-grabbing
      non-integrin (DC-SIGN) (CD209) and their relevance for human cytomegalovirus
      reactivation and disease after allogeneic stem-cell transplantation.
AB  - Promoter variations in Toll-like receptor genes (n = 7) and genes encoding
      pathogen recognition and virus entry receptors (n = 7) were screened to detect
      any association with human cytomegalovirus (hCMV) reactivation and disease in
      patients following allogeneic stem-cell transplantation. Two single nucleotide
      polymorphisms (rs735240, G>A; rs2287886, C>T) in the promoter region of the
      dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN) showed a
      significant association with an increased risk of development of hCMV
      reactivation and disease. Furthermore, these genetic markers influenced the
      expression levels of DC-SIGN on immature dendritic cells, as well as the
      infection efficiency of immature dendritic cells by hCMV, as determined by hCMV
      immediate-early antigen staining. Screening of patients following allogeneic stem
      cell transplantation for the presence of these defined genetic polymorphisms
      might help to predict the individual risk of hCMV reactivation and disease.

PMID- 18076669
TI  - HIV-1 Vpu inhibits accumulation of the envelope glycoprotein within clathrin
      coated, Gag-containing endosomes.
AB  - Several viruses encode ion channels that both modulate the trafficking of
      envelope glycoprotein(s) and stimulate the release of virions from cells. HIV-1
      Vpu enhances virion release and inhibits the endosomal accumulation of the viral
      structural protein Gag. We investigated whether Vpu affects the subcellular
      distribution of Env as well as Gag. Env and Vpu colocalized with each other, in
      part within the trans-Golgi network. In the absence of Vpu, Env accumulated more
      extensively within clathrin-coated endosomal structures. These structures had
      several features consistent with an endosomal viral assembly domain: they
      contained Gag, including proteolytically processed viral matrix protein; the
      tetraspanins CD63 and CD81; the adaptor protein complex AP-3; and AIP1/ALIX, a
      cellular cofactor for viral budding. These endosomes labelled incompletely with
      Env derived from the cell surface, suggesting that some Env reaches this
      compartment without transiting the plasma membrane. Consistent with this,
      endosomal accumulation of Env was not blocked by dominant-negative Eps15, an
      inhibitor of AP-2-mediated endocytosis. Although these data are potentially
      explained by greater endocytosis of mature virions in the absence of Vpu, they
      also raise the possibility that Vpu inhibits the transport of Env and Gag to late
      endosomes, leading to viral assembly at the plasma membrane.

PMID- 18076670
TI  - Detection of new genotypes of Orientia tsutsugamushi infecting humans in
      Thailand.
AB  - PCR screening of blood specimens taken from 195 patients with serologically
      confirmed scrub typhus in three Thai provinces detected the 56-kDa protein
      encoding gene from Orientia tsutsugamushi in ten (5%) patients. Significant
      genetic diversity was found among the ten amplicons, with nine new genotypes
      identified that were different from those found previously in Thailand.
      Phylogenetically, the ten sequences obtained in the present study and sequences
      from 71 strains characterised previously were distributed into several clusters
      that included the Karp, Gilliam, Kuroki, Saitama, Kawasaki and Kato clusters. Two
      of the new genotypes found in the present study clearly belonged to the Karp
      cluster. However, the other new genotypes formed three different clusters,
      including one cluster that appeared to be distant from all previously known
      clusters, and which may therefore be representative of a previously undescribed
      serotype. Other genotypes formed two other clusters that may also be associated
      with undescribed serotypes.

PMID- 18076671
TI  - Comparative bactericidal activities of daptomycin, glycopeptides, linezolid and
      tigecycline against blood isolates of Gram-positive bacteria in Taiwan.
AB  - In-vitro MICs and minimum bactericidal concentrations (MBCs) of daptomycin,
      linezolid, tigecycline, vancomycin and teicoplanin against Gram-positive bacteria
      were determined using the broth microdilution method for ten blood isolates each
      of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S.
      aureus (MRSA), including two vancomycin-intermediate S. aureus (VISA), vancomycin
      resistant Enterococcus faecium and Enterococcus faecalis. One strain of VISA was
      tested in a time-kill synergism assay of daptomycin combined with oxacillin,
      imipenem, rifampicin and isepamicin. Daptomycin showed excellent in-vitro
      bactericidal activity against all the isolates tested, with no tolerance or
      synergism effects when combined with other agents, except with rifampicin against
      VISA. Vancomycin had better bactericidal activity against MRSA and MSSA than did
      teicoplanin. Linezolid had the poorest bactericidal activity against the isolates
      tested, with 100% tolerance by the MSSA and VRE isolates, and 80% tolerance by
      the MRSA isolates. Tolerance towards tigecycline was exhibited by 40% of the MRSA
      isolates, 100% of the MSSA and vancomycin-resistant E. faecalis isolates, and 90%
      of the vancomycin-resistant E. faecium isolates.

PMID- 18076672
TI  - Pharmacodynamic comparison of linezolid, teicoplanin and vancomycin against
      clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci
      collected from hospitals in Brazil.
AB  - Pharmacodynamic exposures, measured as the ratio of steady-state total drug area
      under the curve to MIC (AUC/MIC), were modelled using a 5000-patient Monte-Carlo
      simulation against 119 non-duplicate clinical isolates of Staphylococcus aureus
      and 82 coagulase-negative staphylococci (CNS) collected from hospitals in Brazil
      between 2003 and 2005. Pharmacodynamic targets included an AUC/MIC >82.9 for
      linezolid and >345 for teicoplanin and vancomycin, as well as a free drug AUC/MIC
      >180 for vancomycin. The cumulative fractions of response (CFRs) against all S.
      aureus isolates were 96.0%, 30.1%, 71.6%, 48.0% and 65.1% for linezolid 600 mg
      every 12 h, teicoplanin 400 mg every 24 h and 800 mg every 24 h, and vancomycin
      1000 mg every 12 h and every 8 h, respectively. Using a free drug target for
      vancomycin improved the CFR to 94.6% for the high-dose regimen, but did not
      substantially alter results for the lower dose. CFRs against all CNS isolates
      were 97.8%, 13.4%, 34.6%, 10.9% and 31.3%, respectively, for the same antibiotic
      regimens. The CFR was reduced for all compounds among the methicillin-resistant
      isolates, except for linezolid against methicillin-resistant CNS. Sensitivity
      analyses did not alter the final order of pharmacodynamic potency against these
      isolates. Although higher doses of vancomycin and teicoplanin increased the CFR,
      the likelihood of achieving bactericidal targets was still lower than with
      linezolid. The results for the high-dose vancomycin regimen were highly dependent
      on the pharmacodynamic target utilised. These data suggest that linezolid has a
      greater probability of attaining its requisite pharmacodynamic target than
      teicoplanin and vancomycin against these staphylococci.

PMID- 18076673
TI  - Pediatric restrictive cardiomyopathy associated with a mutation in beta-myosin
      heavy chain.
AB  - Most children do not have a known cause of cardiomyopathy which limits the
      potential for disease-specific therapies. Of the different phenotypic
      presentations of cardiomyopathy, the restrictive form carries the poorest
      prognosis and has the lowest rate of identification of etiology. We present the
      first description of a beta-myosin heavy chain gene mutation in an infant with
      restrictive cardiomyopathy requiring cardiac transplantation. As demonstrated by
      three-dimensional protein structure modeling, the missense mutation is in a
      highly conserved amino acid at the critical binding region for the essential
      light chain. This case emphasizes that mutations in sarcomeric proteins, which
      are known to cause hypertrophic cardiomyopathy in adults, may be associated with
      the development of restrictive physiology in childhood. Identification of the
      genetic basis of pediatric cardiomyopathy has important implications for
      management and genetic counseling.

PMID- 18076674
TI  - Familial 22q11.2 duplication: a three-generation family with a 3-Mb duplication
      and a familial 1.5-Mb duplication.
AB  - We report two familial cases of 22q11.2 duplication detected using multiplex
      ligation-dependent probe amplification (MLPA). In the first case, eight
      individuals from a three-generation family were found to carry a 3-Mb 22q11.2
      duplication. The individuals carrying the duplication show phenotypic variation.
      This phenotypic variation includes heart defect (1 in 8 individuals, 1/8),
      submucous cleft palate (2/8), intellectual disability (2/8), speech delay (2/8),
      behaviour problems (3/8) and brachydactyly (3/8). In the second case, a 1.5-Mb
      22q11.2 duplication was detected in a neonate and her normal mother. The neonate
      presented with severe laryngomalacia causing intermittent stridor. Cranial
      ultrasound showed small subependymal cysts bilaterally. There was no heart defect
      or cleft palate, her chest X ray and renal ultrasound were normal. Review at 2
      months of age revealed normal growth and development. Our findings broaden the
      understanding of 22q11.2 duplication syndrome and demonstrate that MLPA is
      sensitive for detection and sizing of 22q11.2 microduplications.

PMID- 18076675
TI  - Leptin therapy for partial lipodystrophy linked to a PPAR-gamma mutation.
AB  - AIMS/HYPOTHESIS: Partial lipodystrophy (PL) is most commonly characterized by
      loss of subcutaneous fat in the extremities with preservation of truncal fat and
      is associated with insulin resistance, diabetes and hyperlipidaemia. Recombinant
      human leptin (r-metHuLeptin) therapy has been shown to be effective in treating
      metabolic abnormalities associated with congenital or acquired generalized
      lipodystrophy and PL associated with lamin A/C (LMNA) gene mutations or highly
      active antiretroviral therapy (HAART). Our aim was to assess the effectiveness of
      leptin therapy in treating metabolic complications of PL associated with
      heterozygous peroxisome proliferator activated receptor gamma (PPARG) mutations.
      This is the first report to detail the clinical response of a patient with PL due
      to a PPARG mutation treated with r-metHuLeptin. METHODS: A 36-year-old female
      with PL associated with a heterozygous PPARG mutation complicated by poorly
      controlled diabetes and severe, refractory hypertriglyceridaemia was enrolled in
      a National Institutes of Health (NIH) protocol to evaluate the role of r
      metHuLeptin in lipodystrophy. The patient received escalating doses of r
      metHuLeptin until a dose 0.12 mg/kg/day was reached. Metabolic parameters,
      including serum chemistries, fasting blood glucose, glycated haemoglobin (HbA1c),
      lipid profile, an oral glucose tolerance test (OGTT), an insulin tolerance test
      (ITT), liver volume, percentage body fat and energy expenditure were followed at
      regular time intervals over 18 months of therapy. RESULTS: Eighteen months of r
      MetHuLeptin therapy was associated with a marked improvement in glucose
      homeostasis as evidenced by normalization of the fasting blood glucose (baseline
      = 8.3 mmol/l; 18 months = 4.9 mmol/l), lowering of HbA1c (baseline = 9.9%; 18
      months = 7.2%) and improved tolerance to an oral glucose load. In addition, a
      striking amelioration in the patient's refractory, severe hypertriglyceridaemia
      was observed (baseline = 21.15 mmol/l; 18 months = 5.96 mmol/l). CONCLUSION: r
      MetHuLeptin is effective in treating metabolic complications associated with PL
      due to PPARG mutations. In the context of previously published work, our findings
      suggest that the response to r-MetHuLeptin is independent of the aetiology in
      lipodystrophy.

PMID- 18076676
TI  - Photodistributed lichenoid drug eruption secondary to solifenacin.

PMID- 18076677
TI  - Common millet anaphylaxis: a case of a bird-keeper sensitized to millet via
      inhalation, who developed anaphylaxis after oral ingestion.

PMID- 18076678
TI  - Diffuse haemorrhagic bullous amyloidosis with multiple myeloma.

PMID- 18076679
TI  - Rectal melanoma arising in association with neurofibromatosis type I.

PMID- 18076680
TI  - Remission of transient acantholytic dermatosis after the treatment with rituximab
      for follicular lymphoma.

PMID- 18076681
TI  - Generalized pustular eruption in a 5-year-old boy.

PMID- 18076683
TI  - Keratoacanthoma centrifugum marginatum: a rare atypical variant of
      keratoacanthoma.
AB  - Keratoacanthoma centrifugum marginatum (KCM) is an extremely rare variant of
      keratoacanthoma (KA), with about 30 cases reported since it was first described
      in 1962. Clinically, KA is an exoendophytic lesion of 10-25 mm with a horn-filled
      crater that resolves spontaneously within 6 months. In contrast, KCM is
      characterized by a larger diameter continuous centrifugal spread, concurrent
      central atrophy and lack of spontaneous remission. Histologically, KCM is similar
      to KA, with a central keratin-filled crater, overhanging lips of epithelium, a
      sharp outline between the tumour nests and stroma, and lack of anaplasia and
      stroma desmoplasia. We describe a 63-year-old agricultural worker with a 9-month
      history of a multinodular tumour, 70-75 mm in size, on his right hand. The
      clinical diagnosis of KCM was confirmed by histological examination. Local
      radiotherapy proved effective, with no recurrence during a 4-year follow-up.

PMID- 18076682
TI  - Thoracopulmonary actinomycosis: the masquerader.
AB  - Thoracopulmonary actinomycosis can mimic various lung pathologies such as
      bronchogenic carcinoma, tuberculosis and fungal pneumonia, to name but a few. The
      common causative agent is Actinomyces israelii. The disease is successfully
      diagnosed only if there is a high index of suspicion and a thorough evaluation
      with multidisciplinary involvement. We present a case of thoracopulmonary
      actinomycosis in a young immunocompetent man who did not have any predisposing
      illness, and who was treated initially for pulmonary tuberculosis. He showed good
      response to injection crystalline penicillin, which was later changed to oral
      amoxicillin.

PMID- 18076684
TI  - Narrowband ultraviolet B therapy is an effective means of raising serum vitamin D
      levels.

PMID- 18076685
TI  - Bone-marrow oedema syndrome presenting in a patient with atopic eczema.

PMID- 18076686
TI  - How reliable is blood tryptase as a marker of systemic disease in an infant with
      cutaneous mastocytomas?

PMID- 18076687
TI  - Effects of oral isotretinoin therapy on peripheral nerve functions.

PMID- 18076688
TI  - Eczema and X-linked agammaglobulinaemia.
AB  - An 8-year-old boy presented with eczematous skin lesions, recurrent otitis media
      and unexplained pyrexias. X-linked agammaglobulinaemia was diagnosed and
      treatment commenced with intravenous immunoglobulin replacement therapy. X-linked
      agammaglobulinaemia (XLA) is a primary immunodeficiency syndrome associated with
      a deficiency of B lymphocytes, caused by a defect in the expression of Bruton's
      tyrosine kinase. It affects only boys and usually presents before the age of 2
      years with recurrent bacterial sinopulmonary infections. IgG levels are usually
      <2 g/L (normal range 5.4-16.1) and IgM and IgA are usually undetectable. The
      commonest cutaneous features of XLA are pyogenic skin infections; however, eczema
      can occur with increased frequency. We report a child who presented with multiple
      discrete eczematous lesions who subsequently developed eczematous exacerbations
      several days after administration of intravenous immunoglobulin (IVIg)
      replacement therapy.

PMID- 18076689
TI  - Detection of subclinical joint involvement in psoriasis with bone scintigraphy
      and its response to oral methotrexate.
AB  - Subclinical joint involvement in psoriasis has been found with bone scintigraphy.
      In this study, 35 of 50 (70%) patients with psoriasis without clinical
      arthropathy had joint involvement on bone scintigraphy. Patients with positive
      bone scans were started on oral methotrexate, and 20 patients who completed
      treatment had repeat bone scintigraphy. Of the 20 patients, the post-treatment
      bone scans found that 12 (60%) had involvement of different sets of joints, 1
      (5%) had no change and 7 (35%) patients had fewer joints involved. We suggest
      that subclinical joint involvement in psoriasis can be detected with bone
      scintigraphy, and that it is fleeting in nature. A certain degree of treatment
      induced regression of joint involvement on bone scintigraphy may be possible.

PMID- 18076690
TI  - Severe deterioration of psoriasis due to an insulinoma.
AB  - We report a case of a 56-year-old woman who presented with a severe exacerbation
      of psoriasis with concurrent hypoglycaemic episodes. Methotrexate 17.5 mg weekly
      was required to control her psoriasis. Investigation of her hypoglycaemia showed
      raised levels of insulin, C-peptide and proinsulin. Radiological investigation
      showed a tumour at the tail of the pancreas and the diagnosis was insulinoma. A
      spleen-preserving distal pancreatectomy was performed and the hypoglycaemic
      symptoms resolved. Immediately following the pancreatectomy, methotrexate was
      stopped and the patient's psoriasis went into remission. During a 2-year follow
      up, she has required only minimal topical treatment for her skin.

PMID- 18076691
TI  - Nodular lymphangitic subcutaneous dissemination after intralesional antimonial
      treatment for localized cutaneous leishmaniasis.
AB  - Human leishmaniases are protozoan diseases with diverse clinical features. They
      are transmitted by the bites of the Phlebotomus sand fly, and the reservoirs are
      usually wild and domestic animals, particularly dogs. In Spain, Leishmania
      infantum is the causative agent of both cutaneous and visceral leishmaniasis.
      Cutaneous leishmaniasis is a parasitic disease occurring throughout the Americas
      and in the Old World, particularly the Middle East and North Africa. It is spread
      by the female sandfly. We report a 33-year-old man who presented with a solitary
      plaque on the right elbow, which was found to contain Leishmania bodies. He was
      treated with intralesional meglumine antimoniate, but 2 weeks later, several
      subcutaneous nodules were noted on the inner right arm. PCR identified the
      organism as L. infantum. The patient was treated with itraconazole (200 mg/day)
      for 6 weeks was prescribed, which resulted in marked clinical improvement in the
      elbow plaque. However, because of the persistence and lack of response of the
      other lesions, systemic treatment with meglumine antimoniate (20 mg/kg/day)
      intravenously for 7 days and intramuscularly for 13 days was administered. A
      progressive improvement in both cutaneous and subcutaneous lesions was achieved,
      and the lesions resolved completely after 2 months.

PMID- 18076692
TI  - Laser treatment of pigmented lesions in clinical practice: a retrospective case
      series and patient satisfaction survey.
AB  - Lasers are frequently used to treat pigmented skin lesions; however, there is
      little published data from routine clinical practice. We performed a
      retrospective review of patients treated between January 2003 and January 2004 to
      describe the patients, methods used and the clinical outcome. The long-term
      result was determined by a patient questionnaire. In total, 67 patients with 76
      pigmented lesions were treated (22 males and 45 females, mean age 22 years); 27%
      had Fitzpatrick skin types IV-VI. The Q-switched Nd:YAG, and erbium:YAG lasers
      were used in 75% and 24% of cases, respectively, with an average of 5.4
      treatments/patient. The physician-rated outcome at the end of treatment was 'very
      positive' in 45% and 'mostly positive' in 30% of cases. The patient-rated outcome
      at an average of 21 months post-treatment was 'excellent' in 29.5%, 'good' in
      25%, and 'fair' in 22.7% of the 44 cases. About 50% of patients with the three
      most common lesions (congenital naevi, other/unspecified naevi and naevus of Ota)
      achieved good or excellent long-term results.

PMID- 18076693
TI  - A case of atypical sporotrichosis with multifocal cutaneous ulcers.
AB  - We report an atypical case of sporotrichosis in an elderly woman working as a
      horticulturist, who presented with multiple ulcers and nodules on the face and
      the right upper back. Histological examination found numerous small yeast-like
      spores in the granulomatous reaction in the upper dermis. Culture and DNA
      analysis identified Sporothrix schenckii, group B. Misuse of topical steroids and
      self-inoculation may have caused the atypical features found in this patient.

PMID- 18076694
TI  - Subcutaneous sarcoidosis localised to sites of previous desensitizing injections.
AB  - Subcutaneous sarcoidosis is a specific cutaneous lesion of systemic sarcoidosis
      that is rarely reported. Clinically, it is characterized by multiple,
      asymptomatic subcutaneous nodules mainly located on the forearms. Adverse effects
      of desensitization injections mostly consist of local transient reactions.
      Nodular lesions may also develop at the site of injection; these have been
      attributed to the aluminium hydroxide contained by many vaccines. We report a 49
      year old woman with a history of two outbreaks of acute sarcoidosis (Lofgren
      syndrome) in 1994 and 1999, who developed lesions of subcutaneous sarcoidosis in
      the upper part of both arms, at the sites of desensitization injections for
      extrinsic asthma immunotherapy.

PMID- 18076696
TI  - Annular atrophic lichen planus associated with hypertrophic lichen planus.

PMID- 18076695
TI  - Trichilemmal carcinoma with neuroendocrine differentiation.
AB  - We report a 12-mm nodular, cream-coloured skin lesion that appeared on the left
      nasal ala in an 81-year-old man. This trabecular infiltrative tumour showed
      keratin microcysts, stromal hyalization, cytoarchitectural malignancy features,
      colonizing melanocytes, and immunoexpression of epithelial membrane antigen,
      cytokeratin 15/20, chromogranin, synaptophysin and CD56. To our knowledge, this
      is the first documented case of a trichilemmal carcinoma with neuroendocrine
      differentiation and melanocyte colonization, which is suggested by the trabecular
      growth pattern and requires immunohistochemical confirmation. The colonization of
      the epithelial nests by nonatypical dendritic or spindle melanocytes is a clue to
      morphological recognition of pilar neoplasms, along with the presence of stromal
      induction (CD34-positive peritumoral spindle cells), catagen-like apoptotic
      bodies, calcifications, keratin microcysts and cell balls.

PMID- 18076697
TI  - Does ad hoc quality-of-life discussion in inflammatory skin disease consultations
      reflect standardized patient-reported outcomes?
AB  - BACKGROUND: There is little information concerning how much health-related
      quality-of-life (HRQoL) information is elicited in dermatology outpatient
      consultations. OBJECTIVES: To observe and record ad hoc HRQoL discussion in
      inflammatory skin disease consultations, to systematically measure the patient's
      HRQoL and to measure patient satisfaction with dermatology care. METHODS: Clinic
      consultations of patients with inflammatory skin conditions attending a secondary
      care clinic were observed by a single researcher (CP). Data were collected on the
      10 subject areas of the Dermatology Life Quality Index (DLQI) and on sleep,
      burden, frustration and depression. Patients were sent the DLQI and Medical
      Interview Satisfaction Scale (MISS)-21 questionnaires after the consultation.
      RESULTS: In total, 100 consultations were observed (psoriasis n = 50, eczema n =
      17, acne n = 13 and others n = 20). In 26% (n = 26), there was no mention of
      HRQoL issues. In 59% (n = 44), HRQoL discussions were initiated by the clinician.
      In only 26% (n = 19) of consultations were > or = 3 items on the observer's
      checklist raised. In all, 57 evaluable DLQI and MISS-21 questionnaires were
      returned. The mean +/- SD DLQI score was 7.2 +/- 7.0 (n = 18) for patients with
      whom there was no HRQoL discussion and 10.8 +/- 6.7 (n = 39, P = 0.038) for those
      with whom HRQoL was discussed. The mean +/- SD MISS-21 score was 108.8 +/- 16.5
      (n = 18) for the patients with whom there was no HRQoL discussion and 111.3 +/-
      13.6 (n = 39, P = 0.42) for those with whom HRQoL was discussed. The mean +/- SD
      patient expectation score was 5.5 +/- 1.0 (median 5, range 3-7). There was a
      positive correlation between the patient expectation and MISS-21 scores (r(s) =
      0.815, P < 0.0001). CONCLUSIONS: Despite little extent or depth to HRQoL
      discussion, HRQoL issues were raised in the majority of inflammatory skin disease
      consultations. The consultations usually met the patients' expectations and most
      patients were satisfied.

PMID- 18076698
TI  - Three novel mutations of the EDA gene in Chinese patients with X-linked
      hypohidrotic ectodermal dysplasia.

PMID- 18076699
TI  - Chromosomal integration of human herpesvirus 6 DNA in anticonvulsant
      hypersensitivity syndrome.

PMID- 18076700
TI  - The use of dietary manipulation in patients referred to a contact dermatitis
      clinic.

PMID- 18076701
TI  - Telomerase activity in peripheral blood mononuclear cells of psoriatic patients
      correlates with disease severity.

PMID- 18076702
TI  - MDM2 polymorphisms and cancer risk in basal cell carcinoma.

PMID- 18076703
TI  - Successful treatment of extensive human papillomavirus-associated oral
      leucoplakia with imiquimod.

PMID- 18076704
TI  - Analysis of the VCX3A, VCX2 and VCX3B genes shows that VCX3A gene deletion is not
      sufficient to result in mental retardation in X-linked ichthyosis.
AB  - BACKGROUND: X-linked ichthyosis (XLI), an inborn error of metabolism, is due to
      steroid sulphatase (STS) deficiency. Most patients with XLI harbour complete
      deletion of the STS gene and flanking sequences. The presence of low copy number
      repeats on either side of the STS gene seems to have a major role in the high
      frequency of these deletions. Some patients with XLI with terminal deletions of
      Xp22.3 involving marker DXS1139 and the STS gene show mental retardation (MR);
      VCX3A is the only gene located on this critical region. OBJECTIVES: To analyse
      the VCX3A, VCX, VCX2 and VCX3B genes in 80 unrelated Mexican patients with XLI
      with normal intelligence. METHODS: STS activity was measured in the leucocytes
      using 7-[3H]-dehydroepiandrosterone sulphate as a substrate. Amplification of the
      regions from telomeric DXS89 to centromeric DXS1134 including both extremes of
      the STS and the VCX3A, VCX, VCX2 and VCX3B genes was performed using polymerase
      chain reaction. RESULTS: No STS activity was detected in the patients with XLI
      (0.00 pmol mg(-1) protein h(-1)). We observed two different deletion patterns:
      the first group included 62 patients with deletion of VCX3A and VCX genes. The
      second group included 18 patients with breakpoints at several regions on either
      side of the STS gene not including the VCX3A gene. CONCLUSIONS: These data
      indicate that more complex mechanisms, apart from possible VCX3A gene
      participation, are occurring in the genesis of MR in XLI, at least in the sample
      of Mexican patients analysed.

PMID- 18076705
TI  - An open-label phase II study of the safety and efficacy of etanercept for the
      therapy of hidradenitis suppurativa.
AB  - OBJECTIVE: To evaluate the safety and efficacy of etanercept for the management
      of hidradenitis suppurativa. METHODS: In a prospective open-label phase II study,
      etanercept was administered subcutaneously in a dose of 50 mg once weekly for 12
      weeks in 10 patients. They were followed up to 24 weeks and their disease
      activity and Sartorius score were assessed, with also a self-evaluation by visual
      analogue scale (VAS). Disease activity was an assessment of the extent of the
      disease by the attending physicians who were unaware of the protocol. RESULTS: A
      >50% score improvement was found in six patients at week 12 and in seven patients
      at week 24. The VAS was decreased compared with baseline in seven patients at
      week 12 and in six patients at week 24. All changes were statistically
      significant. All patients reported a decrease of local pain at the site of
      lesions after week 4. Drainage of pus from the affected areas recurred in eight
      patients within 4-8 weeks after the end of administration of etanercept. The
      treatment was well-tolerated. CONCLUSIONS: Etanercept is a safe and effective
      therapy for hidradenitis suppurativa and decreases the extent of the disease and
      improves the quality of life. A double-blind, placebo-controlled trial is
      required to elucidate fully the role of etanercept for hidradenitis suppurativa.

PMID- 18076706
TI  - Differential expression of oestrogen receptor isoforms and androgen receptor in
      the normal vulva and vagina compared with vulval lichen sclerosus and chronic
      vaginitis.
AB  - BACKGROUND: Although the expression of the oestrogen receptor (ER) alpha isoform
      and androgen receptor (AR) has been examined in vulval lichen sclerosus (VLS),
      the distribution pattern of ERalpha, ERbeta and AR has not been described in
      chronic atrophic vaginitis nor correlated with markers of proliferation (Ki-67)
      in either of these diseased tissues. OBJECTIVES: To measure the levels and
      distribution of ERalpha, ERbeta and AR immunoreactivity in relation to Ki-67 in
      normal and diseased vulva and vagina. METHODS: The expression of ERalpha, ERbeta
      and AR in relation to the proliferation marker Ki-67 in VLS, squamous hyperplasia
      of the vulva and chronic atrophic vaginitis was determined by
      immunohistomorphometric analysis and compared with that in normal vulva and
      vagina. RESULTS: VLS showed similar ERalpha and ERbeta expression in the
      'epidermal' and 'dermal' tissue layers to that of normal vulvae, whereas AR
      expression appeared to be absent in most cases. ERbeta and Ki-67 expression was
      correlated with ERalpha expression but only in the 'fibrovascular' layer of the
      vulva. ERalpha expression was absent from the 'fibromuscular' layer of diseased
      vulvae, while ERbeta expression was absent in normal tissues but was highly
      expressed in diseased vulvae. ERalpha expression was significantly correlated
      with AR expression in the fibrovascular layer of the vagina and inversely
      correlated with Ki-67 staining in the parabasal cells of the epidermis in
      patients with chronic atrophic vaginitis. CONCLUSIONS: These data suggest that ER
      expression and levels may be implicated in the aetiopathology of VLS and chronic
      atrophic vaginitis.

PMID- 18076707
TI  - Gadolinium-induced nephrogenic systemic fibrosis in a patient with an acute and
      transient kidney injury.
AB  - Nephrogenic systemic fibrosis (NSF) describes a characteristic fibrosing disorder
      which typically presents with indurated plaques on the trunk and extremities of
      patients with advanced renal disease. We present a case of biopsy-confirmed NSF
      in a patient with severe acute kidney injury with no prior history of renal
      disease. A 64-year-old man with an acute and severe decrease in glomerular
      filtration rate underwent magnetic resonance imaging studies with gadolinium
      contrast (Omniscan) and subsequently developed NSF. His renal disease had
      normalized at the time his skin disease developed. Skin biopsies revealed
      findings of NSF and scanning electron microscopy with energy-dispersive X-ray
      spectroscopy confirmed insoluble gadolinium within lesional tissue.

PMID- 18076708
TI  - Exhaled nitric oxide in childhood asthma: a review.
AB  - As an 'inflammometer', the fraction of nitric oxide in exhaled air (Fe(NO)) is
      increasingly used in the management of paediatric asthma. Fe(NO) provides us with
      valuable, additional information regarding the nature of underlying airway
      inflammation, and complements lung function testing and measurement of airway
      hyper-reactivity. This review focuses on clinical applications of Fe(NO) in
      paediatric asthma. First, Fe(NO) provides us with a practical tool to aid in the
      diagnosis of asthma and distinguish patients who will benefit from inhaled
      corticosteroids from those who will not. Second, Fe(NO) is helpful in predicting
      exacerbations, and predicting successful steroid reduction or withdrawal. In
      atopic asthmatic children Fe(NO) is beneficial in adjusting steroid doses,
      discerning those patients who require additional therapy from those whose
      medication dose could feasibly be reduced. In pre-school children Fe(NO) may be
      of help in the differential diagnosis of respiratory symptoms, and may
      potentially allow for better targeting and monitoring of anti-inflammatory
      treatment.

PMID- 18076709
TI  - A drop of vitriol: microspherocytosis following sulphuric acid exposure.

PMID- 18076710
TI  - Frequency and spectrum of central nervous system involvement in 193 children with
      haemophagocytic lymphohistiocytosis.
AB  - Haemophagocytic lymphohistiocytosis (HLH) may cause meningoencephalitis and
      significant neurological sequelae. We examined the relationship between
      neurological symptoms and cerebrospinal fluid (CSF) at diagnosis, and long-term
      outcome, in all children enroled in the HLH-94-study prior to July 1, 2003, for
      whom information on CSF at diagnosis was available (n = 193). Patients were
      divided into four groups: (i) normal CSF (cells/protein) and no neurological
      symptoms (n = 71); (ii) normal CSF but neurological symptoms (n = 21); (iii)
      abnormal CSF but no symptoms (n = 50); and (iv) abnormal CSF with neurological
      symptoms (n = 51). At diagnosis, neurological symptoms were reported in 72/193
      (37%) (seizures = 23); abnormal CSF in 101/193 (52%), and either or both in
      122/193 (63%). Altogether 16/107 (15%) survivors had neurological sequelae at
      follow-up (median 5.3 years). Multivariate hazard ratios (HR) for mortality were
      0.98 [95% confidence interval (CI) = 0.42-2.31], 1.52 (0.82-2.82) and 2.05 (1.13
      3.72) for groups 2-4, compared with group 1. Moreover, sequelae were more
      frequent in group 4 (7/21, 33%) compared to groups 1-3 (9/86, 10%) (P = 0.015).
      Patients with abnormal CSF at diagnosis had significantly increased mortality [HR
      = 1.78 (95% CI = 1.08-2.92), P = 0.023]. Thus, a substantial proportion of HLH
      survivors suffer neurological sequelae, and children with abnormal CSF have
      increased risk of mortality and neurological sequelae. Prompt treatment of HLH at
      onset or relapse may reduce these complications.

PMID- 18076712
TI  - Cervical thymic hyperplasia after chemotherapy in an adult patient with Hodgkin
      lymphoma: a potential cause of false-positivity on [18F]FDG PET/CT scanning.

PMID- 18076711
TI  - The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for
      multiple myeloma.
AB  - Aurora kinases are potential targets for cancer therapy. Previous studies have
      validated Aurora kinase A as a therapeutic target in multiple myeloma (MM), and
      have demonstrated in vitro anti-myeloma effects of small molecule Aurora kinase
      inhibitors that inhibit both Aurora A and B. This study demonstrated that Aurora
      B kinase was strongly expressed in myeloma cell lines and primary plasma cells.
      The selective Aurora B inhibitor AZD1152-induced apoptotic death in myeloma cell
      lines at nanomolar concentrations, with a cell cycle phenotype consistent with
      that reported previously for Aurora B inhibition. In some cases, AZD1152 in
      combination with dexamethasone showed increased anti-myeloma activity compared
      with the use of either agent alone. AZD1152 was active against sorted CD138(+) BM
      plasma cells from myeloma patients but also, as expected, was toxic to CD138(-)
      marrow cells from the same patients. In a murine myeloma xenograft model, AZD1152
      inhibited tumour growth at well-tolerated doses and induced cell death in
      established tumours, with associated mild, transient leucopenia. AZD1152 shows
      promise in these preclinical studies as a novel treatment for MM.

PMID- 18076713
TI  - The ADHD Tetragrammaton taken in vain in neurogenetic disorders?

PMID- 18076714
TI  - School stressors, psychological complaints and psychosomatic pain.
AB  - BACKGROUND: The proportion of Scandinavian school children reporting
      psychosomatic pain and psychological complaints have increased in recent decades.
      In this study we investigated these symptoms in relation to potential stressors
      in the school environment. METHODS: A cross-sectional study was conducted based
      on child interviews linked to nationally representative household surveys in
      Sweden during 2002-2003 covering a sample of 2588 children aged 10-18 years. The
      main outcome variable of psychosomatic pain signified suffering from headache as
      well as recurrent abdominal pain on a weekly basis. RESULTS: School stressors,
      such as harassment by peers, schoolwork pressure and being treated poorly by
      teachers, were associated with psychosomatic pain as well as psychological
      complaints such as sadness, irritability, feeling unsafe and nervous. Harassment
      was identified as a particularly important determinant with adjusted odds ratios
      (ORs) ranging from 3.1 to 8.6 for psychosomatic pain. All psychological
      complaints were associated with psychosomatic pain with adjusted ORs ranging from
      2.2 to 3.7, and mediated most of the association of harassment to psychosomatic
      pain. CONCLUSIONS: School stressors are strongly associated with psychosomatic
      pain and psychological complaints in school children. Psychological complaints
      seem to function as mediators in the association of school stressors to
      psychosomatic pain symptoms to a great extent.

PMID- 18076715
TI  - Current transfusion practices for platelets and fresh, frozen plasma in UK
      tertiary level neonatal units.

PMID- 18076716
TI  - Varicella-related deaths in children and adolescents--Germany 2003-2004.
AB  - AIM: Although varicella is acknowledged as a rare cause of death in children,
      there are few comprehensive data with respect to the clinical course leading to
      death. METHODS: A nationwide, active surveillance was carried out in Germany for
      children up to age 17 years who were admitted to a paediatric hospital for
      varicella or associated complications, including deaths. RESULTS: A total of 10
      children with varicella-associated death were reported over period of 2 years,
      yielding a mortality rate of 0.4/1 000 000 children per year. Three deaths
      occurred in children diagnosed with acute lymphocytic leukaemia and disseminated
      varicella, two shortly after diagnosis of leukaemia and therefore not
      preventable, and one during remission with an untypical presentation. Two
      children died with a congenital varicella syndrome. There was no death in
      children with neonatal varicella. Four other cases were related to varicella
      pneumonia or septicaemia and one to myocarditis. CONCLUSION: In a population with
      no general varicella vaccination programme, varicella accounted for a small but
      not negligible risk for death in immunocompetent and immunocompromised children.
      Together these data point to the importance of a thoroughly implemented, general
      varicella vaccination programme.

PMID- 18076717
TI  - Renal concentrating capacity as a marker for glomerular filtration rate.
AB  - AIM: We have studied 160 children with a variety of renal diseases, 14 of them
      with chronic renal failure (CRF), to evaluate maximum urinary osmolality as a
      predictor of glomerular filtration rate (GFR) testing the hypothesis that a
      normal GFR is necessary to have a normal urinary concentrating capacity. METHODS:
      All patients had a serum creatinine measured. GFR was calculated according to the
      Schwartz formula. All patients underwent desmopressin (DDAVP) test to evaluate
      renal concentrating capacity. RESULTS: Patients with CRF were unable to
      concentrate the urine beyond 486 mosm/kg whereas all patients with a normal
      concentrating capacity (urine osmolality >835 mosm/kg) had a normal GFR.
      Desmopressin test sensitivity to detect CRF was 100% and specificity 70.5%. A
      significant negative correlation was found between urinary osmolality after DDAVP
      administration and serum creatinine levels and between urinary volume corrected
      by 100 mL of GFR (V/GFR) and urinary osmolality. CONCLUSION: In our series, a
      normal concentrating capacity was always associated with a normal GFR while all
      patients with decreased GFR had a concentrating capacity defect. Thus, in the
      evaluation of infants and children with renal disease, the finding of a normal
      urinary concentrating capacity will suggest and intact glomerular and tubular
      function.

PMID- 18076718
TI  - Antimicrobial usage in paediatric intensive care units in China.
AB  - AIM: The aim of the study was to determine antimicrobial usage in paediatric
      intensive care units (PICUs) in China. METHODS: Data were equally collected from
      540 charts of PICUs in the three Chinese tertiary teaching children hospitals in
      2006. The data included demographic, clinical data and those on antimicrobial
      usage and results of microbiological examinations. RESULTS: Of the 540 cases, 524
      (94.7%) patients received at least one antimicrobial agent. The main treatment
      started empirically in 387 (71.6%). The third-generation cephalosporins were the
      major antimicrobials used in all participating hospitals, accounting for 227
      (31%). Bacteria were isolated from 48%, 68% and 59% of the three PICUs. Six
      common pathogens accounted for more than 75% of the isolated bacteria. The rates
      of Escherichia coli isolates resistant to cefotaxime were 73.8%, 58.3% and 49.2%,
      respectively, with the rate being higher in H1 than in H2 and H3 (both p<0.01).
      CONCLUSIONS: Irrational use of antimicrobials exists in clinical practice of
      PICUs in China. It is recommended that antimicrobial usage should be guided by
      bacterial isolation and antimicrobial susceptibility tests in order to select
      correct antimicrobials and to prevent emergency of drug-resistant strains in
      PICUs.

PMID- 18076719
TI  - Mortality in childhood progressive encephalopathy from 1985 to 2004 in Oslo,
      Norway: a population-based study.
AB  - AIMS: The aims were to estimate case fatality and survival rates, standardized
      mortality ratio (SMR), and independent prognostic factors for survival, in a
      population-based cohort of progressive encephalopathy (PE) patients. METHODS: We
      divided onset of disease into neonatal and postneonatal groups and aetiology into
      metabolic (n=55), neurodegenerative (n=27) and HIV encephalopathy (n=2) groups.
      Case fatality was the number of deaths divided by the number of patients.
      Cumulative survival probability at 10 years of follow-up and independent risk
      factors for mortality were analyzed using the Kaplan-Meier survival curve and the
      Cox model. RESULTS: Case fatality was 36.9% and the mean and median follow-up
      times were 3109 and 2887 days. At 1 and 10 years, the cumulative probability of
      survival was 81% and 66%. Neonatal onset showed increased risk of death compared
      to postneonatal onset (RR 3.0; 95% CI 1.4-6.2). Metabolic aetiology showed
      increased risk of death compared to other aetiology (RR 1.25; 95% CI 1.10-1.46).
      The SMR of 37.7 for boys and 23.8 for girls was significantly increased (p<0.001)
      compared to the total Norwegian population stratified by gender and age.
      CONCLUSIONS: Children with PE showed a vast excess in mortality compared to the
      general population stratified by gender and age. Neonatal presentation and
      metabolic aetiology were the most significant factors for increased risk of
      death.

PMID- 18076720
TI  - Assessment of the prevalence of microaspiration by gastric pepsin in the airway
      of ventilated children.
AB  - AIM: Mechanically ventilated patients are at risk for aspiration of gastric
      contents. The aim of this observational study was to determine the prevalence of
      micro-aspiration in children with cuffed and uncuffed endotracheal (ET) tubes and
      with tracheostomies and to assess the effect of feeding status on aspiration.
      Micro-aspiration was determined by measuring gastric pepsin in tracheal
      aspirates. METHODS: We studied 27 children on ventilators in paediatric intensive
      care unit (PICU) and 10 children undergoing elective surgeries for various
      indications. Tracheal aspirates were collected from children on ventilatory
      support in the intensive care unit during medically indicated suctioning and from
      the group of children undergoing elective surgery in the operation room. Pepsin
      was detected by enzymatic assay. RESULTS: Overall 70% of cases in PICU were
      positive for pepsin in at least one of the aspirates. Pepsin positivity was
      significantly lower in the cuffed group than in the uncuffed and tracheostomy
      groups. Tube feedings did not significantly influence the prevalence of pepsin
      positivity. CONCLUSIONS: Measurement of gastric pepsin in tracheobronchial fluid
      is a sensitive tool to detect aspirations in mechanically ventilated children and
      to assess the efficacy of preventive measures in PICU settings.

PMID- 18076721
TI  - Informing state-level health policy in India: the case of childhood immunizations
      in Maharashtra and Bihar.

PMID- 18076722
TI  - Lupin sensitization and clinical allergy in food allergic children in Norway.
AB  - AIM: The aim of the present pilot study was to investigate to what extent
      children in Norway sensitized to lupin had clinical lupin allergy, and to compare
      sensitization to lupin with sensitization to other legumes. METHODS: Thirty-five
      children with food allergy referred to a national referral hospital were
      evaluated with skin prick test (SPT) and analysis of serum-specific IgE to lupin,
      peanut, pea and soy. The children with positive SPTs to lupin were offered oral
      food challenges with lupin flour. RESULTS: Fifteen children (43%) had positive
      SPT and 17 children (49%) had serum-specific IgE to lupin. Ten SPT-positive
      children underwent oral food challenges and one experienced an allergic reaction
      to lupin flour. This child was one of six challenged children with IgE antibodies
      to peanut >15 kU(A)/L. There was a strong relationship between positive SPT to
      lupin flour and positive SPT to soy and between positive SPT to lupin and
      specific IgE to soy, pea and peanut. CONCLUSIONS: Children with sensitization to
      lupin are not likely to have a clinical lupin allergy. Avoidance of lupin on the
      basis of lupin sensitization or peanut allergy would lead to unnecessarily strict
      diets. Food challenge is currently necessary to diagnose lupin allergy.

PMID- 18076723
TI  - Radiographic follow-up of community-acquired pneumonia in children.
AB  - AIM: To evaluate the value of radiographic follow-up of community-acquired
      pneumonia in children who are previously healthy. METHODS: Patient records for
      the years 2003 and 2004 at the Ulleval University Hospital in Oslo were reviewed,
      and a total of 245 children were selected for the study. Radiographs were
      evaluated by two paediatric radiologists independently. RESULTS: One hundred and
      thirty-three patients had control radiographs, of which 106 were normal and 27
      were abnormal. Only three of 27 patients with abnormal findings had further
      clinical problems that could be related to the pneumonia. Two of 106 with normal
      findings had further clinical problems, despite the normal control radiograph. Of
      the 112 without radiographic follow-up, 10 had subsequent clinical problems, but
      most occurred within the first 4 weeks after discharge, before controls would
      have been scheduled. There were five patients who may have benefited from
      controls. One relapse could theoretically have been prevented. Four patients were
      cases for whom the pneumonias were the first manifestations of chronic lung
      disease. Such patients may have some benefit from control radiographs, but only
      in terms of detecting the chronic disease at an earlier stage, not in altering
      the clinical course. Such modest benefits must be weighed against the
      consequences of providing follow-up to a large number of healthy children, and
      making lots of abnormal findings with no clinical significance. CONCLUSION:
      Control radiographs are not very valuable in children who are otherwise healthy.

PMID- 18076724
TI  - Reported symptoms of food hypersensitivity and sensitization to common foods in 4
      year-old children.
AB  - AIM: To characterize reported food hypersensitivity (FHS) among young children in
      a birth cohort. METHODS: At 4 years of age a parental questionnaire on FHS and
      allergic symptoms was evaluated. Blood was collected for analyses of IgE
      antibodies to egg, milk, fish, wheat, peanut and soy. Complete questionnaire data
      was available for 3694 children (90%), and blood samples were obtained from 2563
      children (63%). RESULTS: FHS was reported in 11% of the children (n=397). Eczema
      was the most commonly reported symptom and the only symptom in half of these
      children. Food-related reactions from the airways, facial oedema or urticaria
      were reported in 198 children, and the majority of these children (75%) reported
      multiple symptoms. Furthermore, a combination of airway symptoms, facial oedema
      or urticaria together with sensitization to food suggested a more severe form of
      FHS. This was found in 1.6% of all children. Symptoms caused by peanut were
      closely associated with sensitization to peanut (p<0.001). CONCLUSIONS: FHS in 4
      year-old children with any of asthma, rhino-conjunctivitis, facial oedema or
      urticaria in combination is in most cases associated to sensitization to food.
      This phenotype of FHS is likely to represent a more severe form of FHS.

PMID- 18076725
TI  - Correlation between spirometry and impulse oscillometry in children with asthma.
AB  - AIM: In certain patients, such as young children or individuals with cerebral
      palsy or severe mental retardation, it is difficult to perform forced expiratory
      manoeuvres to measure expiratory flow volume. In such cases, we could evaluate
      obstructive lung disease through the measurement of airway resistance instead of
      expiratory flow volume. METHODS: In this study, we evaluated the correlation of
      Impulse Oscillometry (IOS) parameters with spirometry values and peak expiratory
      flow rate (PEFR) measurements to give coherence to IOS recordings in lung
      function exploration. Total serum IgE levels, total eosinophil counts and
      specific IgE levels were measured in 48 children with asthma and 66 control
      subjects, aged 7-15 years of age. IOS, spirometry and PEFR measurements were
      performed, as well as methacholine challenge. We further analyzed the
      correlations in atopic asthma, atopic control, nonatopic asthma and nonatopic
      control groups. RESULTS: FEV(1) and PEFR showed a significant correlation with
      impedance and resistance (R) at 5, 10, 20 and 35 Hz, both in atopic asthmatic and
      in atopic control children. FVC also showed a correlation with impedance and R at
      10, 20 and 35 Hz, both in atopic asthmatic and atopic control children. FEF(25
      75%) did not show a correlation with resistances. CONCLUSION: FEV(1), FVC and
      PEFR were significantly correlated with IOS parameters, in both asthmatic and
      control subjects, especially for atopic children. IOS could be used as a suitable
      measure of lung function when spirometry and PEF cannot be performed.

PMID- 18076726
TI  - In vivo confocal microscopy in a patient with recurrent conjunctival
      intraepithelial neoplasia.

PMID- 18076727
TI  - Health status and life satisfaction after decompressive craniectomy for malignant
      middle cerebral artery infarction.
AB  - OBJECTIVES: To study the long-term outcome in patients with malignant middle
      cerebral artery (MCA) infarction treated with decompressive craniectomy. The
      outcome is described in terms of survival, impairment, disabilities and life
      satisfaction. MATERIALS AND METHODS: Patients were examined at a minimum of 1
      year (mean 2.9, range 1-6) after the surgery and classified according to the
      Glasgow Outcome Scale (GOS), the National Institutes of Health Stroke scale
      (NIHSS), the Barthel Index (BI), the short-form health survey (SF-36) and the
      life satisfaction checklist (LiSat-11). RESULTS: Eighteen patients were included.
      The long-term survival was 78%. The mean NIHSS score was 13.8 (range 6-20). No
      patient was left in a vegetative state. The mean BI was 63.9 (5-100). The SF-36
      scores showed that the patients' view of their health was significantly lower in
      most items compared with that of a reference group. According to the LiSat
      checklist, 83% found their life satisfying/rather satisfying and 17% found their
      life rather dissatisfying/dissatisfying. CONCLUSION: We conclude that the
      patients remained in an impaired neurological condition, but had fairly good
      insight into their limitations. Although their life satisfaction was lower
      compared with that of the controls, the majority felt that life in general could
      still be satisfying.

PMID- 18076728
TI  - Anti-proliferative and anti-remodelling effect of beclomethasone dipropionate,
      formoterol and salbutamol alone or in combination in primary human bronchial
      fibroblasts.
AB  - BACKGROUND: Bronchial asthma is characterized by lower airway inflammation and
      remodelling. Anti-inflammatory treatment with inhaled corticosteroids (ICS)
      provides the mainstay of asthma therapy together with bronchodilation induced by
      short- and long-acting inhaled beta(2)-agonists. Lower airway fibroblasts may
      play a critical role in airway inflammation and remodelling, suggesting that they
      might represent an important target for the major anti-asthmatic drugs. The aim
      of our study was to investigate the effects of beclomethasone dipropionate (BDP),
      salbutamol and formoterol either alone or in combination on in vitro cultures of
      human bronchial fibroblasts. METHODS: Fibroblasts were cultured in the presence
      of pro-inflammatory and proliferative stimuli, BDP, salbutamol and formoterol.
      The effects of drugs on cell proliferation were ascertained by (3)H-thymidine
      incorporation. CD90 and CD44 expression were detected by flow cytometry and
      fibronectin secretion using the enzyme-linked immunosorbent assay technique.
      RESULTS: This study showed that BDP alone has significant anti-proliferative
      effects on lung fibroblasts treated with basic fibroblast growth factor and the
      combination of BDP with formoterol or salbutamol strengthen these effects. Short
      acting beta(2)-agonist (SABA) or long-acting beta(2)-agonist (LABA) by themselves
      did not show any significant effect on the different cultures. CD44 and CD90
      expression and fibronectin production were modulated by pro-inflammatory and
      proliferative stimuli; the addition of the drugs brought them back near to the
      basal level. CONCLUSIONS: From this in vitro study, we can conclude that BDP,
      when combined with salbutamol or formoterol, exhibits enhanced anti-remodelling
      activity in bronchial fibroblasts, providing new insights on the additive effects
      of ICS and SABAs and LABAs for asthma therapy.

PMID- 18076729
TI  - Anaphylactic shock because of sublingual immunotherapy overdose during third year
      of maintenance dose.

PMID- 18076730
TI  - Long-term effect of magnesium consumption on the risk of symptomatic gallstone
      disease among men.
AB  - BACKGROUND: Magnesium deficiency can cause dyslipidemia and insulin
      hypersecretion, which may facilitate gallstone formation. However, the effect of
      long-term consumption of magnesium on the risk of gallstone disease is unknown.
      METHODS: We prospectively studied magnesium consumption and risk of gallstone
      disease in a cohort of 42,705 U.S. men from 1986 to 2002. Magnesium consumption
      was assessed using a validated semiquantitative food frequency questionnaire.
      Newly diagnosed gallstone disease was ascertained biennially. RESULTS: We
      documented 2,195 incident cases of symptomatic gallstones during 560,810 person
      years of follow-up. The age-adjusted relative risks (RRs) for men with total
      magnesium intake and dietary magnesium, when the highest and lowest quintiles
      were compared, were 0.67 (95% confidence interval [CI] 0.59-0.77, P for trend
      <0.0001) and 0.67 (CI 0.59-0.76, P for trend <0.0001), respectively. After
      adjusting for multiple potential confounding variables, when extreme quintiles
      were compared, the multivariate RR of total magnesium intake (RR 0.72, CI 0.61
      0.86, P for trend = 0.006) and dietary magnesium (RR 0.68, CI 0.57-0.82, P for
      trend = 0.0006) remained significant with a dose-response relationship.
      CONCLUSIONS: Our findings suggest a protective role of magnesium consumption in
      the prevention of symptomatic gallstone disease among men.

PMID- 18076731
TI  - Pancreatitis risk in primary hyperparathyroidism: relation to mutations in the
      SPINK1 trypsin inhibitor (N34S) and the cystic fibrosis gene.
AB  - OBJECTIVE: Primary hyperparathyroidism (pHPT)-related hypercalcemia is considered
      to represent a risk factor for the development of pancreatitis. We therefore
      explored whether mutations in genes that were previously identified to increase
      the risk for pancreatitis coexist in a cohort of 826 patients with pHPT
      prospectively studied between 1987 and 2002. METHODS: Among 826 patients with
      pHPT, 38 patients were identified with pancreatitis (4.6%). DNA was available
      from 25 patients (13 women/12 men, 16 acute pancreatitis/9 chronic pancreatitis).
      These individuals and 50 patients with pHPT without pancreatitis were analyzed
      for mutations in the serine protease inhibitor Kazal type I (SPINK1) gene (N34S)
      and the cationic trypsinogen gene (PRSS1) (N29I, R122H) by melting curve analysis
      and DNA sequencing. Sequence analysis of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene was carried out for the detection of 36
      mutations and the Tn polymorphism. RESULTS: Four of 25 patients with pHPT and
      pancreatitis carried the N34S missense mutation in the SPINK1 gene (16%), while
      all 50 controls (pHPT without pancreatitis) showed no mutation in SPINK1 or PRSS1
      genes (P < 0.05 vs controls, P < 0.001 vs general population). CF-causing CFTR
      mutations were present in four patients (P < 0.05 vs general population), while
      one patient carried a 5T allele. One patient was transheterozygous (SPINK1:
      N34S/CFTR: R553X). Mean serum calcium levels in pancreatitis patients (3.1
      mmol/L) did not differ significantly from the mean of the entire cohort (3.0
      mmol/L) or pHPT patients without pancreatitis (3.1 mmol/L). CONCLUSION:
      Pancreatitis risk is approximately 10-fold elevated in pHPT, but pancreatitis
      occurs infrequently. This indicates an existing but minor impact of pHPT-related
      hypercalcemia. If pancreatitis occurs, it seems associated with genetic risk
      factors such as mutations in the SPINK1 and CFTR genes. In contrast, a
      combination of both hypercalcemia and genetic variants in SPINK1 or CFTR
      increases the risk to develop pancreatitis in patients with pHPT.

PMID- 18076732
TI  - Warm water or oil-assisted colonoscopy: toward simpler examinations?
AB  - OBJECTIVES: Completion rates, pain, and difficulties during the exam are still
      problems in colonoscopy. New methods of lubrication, rarely considered a matter
      of study, may help in this respect. Our aim was to compare an oil-assisted
      technique with a modified warm water method applied during colonoscopy. METHODS:
      A prospective, randomized, and controlled study was planned in which three groups
      of patients were submitted to colonoscopy: a standard lubricating method (water
      soluble jelly: group A, 170 patients) was adopted in a control group, whereas the
      standard method plus injection into the colon of corn seed oil (group B, 170
      patients) or warm water (group C, 170 patients) were employed in the other
      groups. The main variables evaluated were: the success rate for total intubation,
      the time required to reach the cecum and the time needed to examine the colon at
      withdrawal, and the level of pain and degree of difficulty associated with the
      examination. RESULTS: Successful intubation to the cecum was significantly more
      frequent (P < 0.01 and P < 0.001, respectively) in the oil group (group B,
      155/166) and in the warm water group (group C, 156/163) than in the control group
      (group A, 138/164), and less time was needed (P < 0.001); no significant
      difference was found between group B and C. Furthermore, no significant
      differences were found with regard to time for examination at withdrawal among
      the three groups. Level of pain and degree of difficulty during colonoscopy were
      significantly lower in the oil (P < 0.001) and in the warm water (P < 0.001)
      groups than in the control group, but no significant difference was found between
      group B and C. Neither side effects were observed for patients nor damage to the
      instrument. CONCLUSIONS: Warm water and oil-assisted colonoscopy could be simple,
      safe, and inexpensive methods for easier and less painful examinations.

PMID- 18076733
TI  - Influence of malpractice history on the practice of screening and surveillance
      for Barrett's esophagus.
AB  - BACKGROUND: Gastroenterologists' approach to surveillance for Barrett's esophagus
      is variable. We hypothesized that financial incentives and concerns over
      malpractice litigation influence gastroenterologists' usual practices regarding
      screening and surveillance. METHODS: We surveyed gastroenterologists (N = 224)
      regarding their usual practice of screening or surveillance for Barrett's
      esophagus, belief in the efficacy of screening, knowledge of published
      guidelines, demographic factors, compensation structure, volume of endoscopies,
      and malpractice history. Practices were characterized as aggressive or
      conservative in the utilization of services compared with a published guideline.
      RESULTS: Twenty-one percent of attending gastroenterologists reported being
      identified as a defendant in at least one malpractice suit. Prior malpractice
      defendants had practiced gastroenterology longer and performed a higher volume of
      endoscopies, but had similar knowledge regarding published screening guidelines
      to those who had not been defendants. They were more likely to be aggressive
      rather than conservative in screening and surveillance for Barrett's esophagus
      (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.1-12), and remained so after
      controlling for other factors. In particular, they were more likely to recommend
      screening for populations with a lower risk of development of cancer, and to
      perform more frequent surveillance for low-grade dysplasia. Other factors were
      not associated with aggressive practice, including compensation structure.
      CONCLUSIONS: History of at least one prior malpractice suit appears to be
      associated with the more aggressive use of endoscopic screening and surveillance
      for Barrett's esophagus, irrespective of physician belief regarding the efficacy
      of that strategy in reducing mortality. Hypervigilance and fear of future
      malpractice suits may drive this increased use.

PMID- 18076734
TI  - Esophageal dilated intercellular spaces (DIS) and nonerosive reflux disease.
AB  - Esophageal mucosal dilated intercellular spaces (DIS) are frequently observed in
      patients with nonerosive reflux disease (NERD) and patients with esophagitis. The
      specificity of DIS is questionable, as it is present in up to 30% of asymptomatic
      healthy subjects and in patients with other esophageal disorders. DIS occurs in
      parallel with a drop in potential difference, diminished transepithelial
      resistance, and increased esophageal mucosal permeability. These alterations
      arise with exposure to acid and pepsin during gastroesophageal reflux, but the
      exact pathway of damage to the intercellular junctions remains unclear and seems
      to be multifactorial. Other noxious contents of the refluxate, such as bile
      acids, are harmful and DIS can also be induced by acute psychological stress. DIS
      can be assessed quantitatively with electron microscopy (EM), but it is also
      recognizable with light microscopy (LM). DIS can disappear after treatment with
      proton pump inhibitors (PPI); however, this is not the case in all NERD patients.
      A recent study showed that patients with NERD who are refractory to PPI might
      still have DIS; and animal experiments showed that persistence of DIS might be
      due to esophageal mucosal exposure to bile acids and/or psychological stress. In
      conclusion, DIS is a frequent but nonspecific histological feature of NERD. It
      can be caused by acid reflux, but bile acids in the refluxate and/or
      psychological stress can modulate the development or persistence of DIS. Although
      a causal relationship between DIS and heartburn has been proposed, it still needs
      to be proven and the underlying mechanisms investigated before considering DIS as
      a target for treatment of NERD.

PMID- 18076735
TI  - Gastrointestinal manifestations of amyloidosis.
AB  - Amyloidosis is characterized by extracellular deposition of abnormal protein.
      There are six types: primary, secondary, hemodialysis-related, hereditary,
      senile, and localized. Primary (AL) amyloidosis is associated with monoclonal
      light chains in serum and/or urine with 15% of patients having multiple myeloma.
      Secondary (AA) amyloidosis is associated with inflammatory, infectious, and
      neoplastic diseases. The presentation is protean, including macroglossia, a
      dilated and atonic esophagus, gastric polyps or enlarged folds, and luminal
      narrowing or ulceration of the colon. Amyloid deposition in the gastrointestinal
      (GI) tract is greatest in the small intestine. The symptoms include diarrhea,
      steatorrhea, or constipation. Pseudo-obstruction carries a particularly grave
      prognosis, often not responding to pro-motility agents. Hepatic involvement is
      common, but the clinical manifestations are usually mild with hepatomegaly and an
      elevated alkaline phosphatase level. Biopsies to diagnose amyloidosis can be
      taken from the fat, kidney, intestine, or bone marrow. The safety of liver
      biopsies is controversial. With Congo Red stain, amyloid appears red in normal
      light and apple-green in polarized light. Treatment for AL amyloidosis is
      chemotherapy and stem cell transplantation; treatment for AA amyloidosis is
      control of the underlying disease. Amyloidosis should be considered in patients
      with proteinuria, cardiomyopathy, hepatomegaly (with mildly abnormal liver
      tests), peripheral and autonomic neuropathy, weight loss, and GI symptoms.

PMID- 18076736
TI  - Permanent work disability in Crohn's disease.
AB  - OBJECTIVE: Crohn's disease (CD) frequently presents during early adulthood, a
      peak time of work productivity. There are limited data from the United States on
      work disability from CD. We performed this study to identify clinical factors
      associated with permanent work disability in a CD tertiary referral cohort.
      METHODS: Cases were identified as patients who received permanent work disability
      compensation from the social security administration (SSA) related to CD. Four
      control patients who were not receiving work disability were selected for each
      case. Multivariate logistic regression was performed to identify characteristics
      that were independently associated with work disability. RESULTS: A total of 737
      patients with CD were seen in our center, and 185 CD patients were included in
      our study (37 disability cases, 148 controls). On multivariate analysis, an SIBDQ
      score <or=50 (OR 12.44, 95% CI 4.45-34.79), undergoing two or more GI surgeries
      (OR 7.09, 95% CI 2.63-19.11), and two or more medical hospitalizations (OR 2.76,
      95% CI 1.03-7.37) were significantly associated with work disability in CD.
      Disease location (small bowel vs colon), type (inflammatory, stricturing, or
      fistulizing), or specific treatment strategies were not associated with work
      disability in our analysis. CONCLUSION: Permanent work disability administered
      through social security was encountered in 5.3% of the Crohn's patients followed
      in our cohort. Patients who consistently report low quality of life, or have
      frequent flares requiring surgical intervention or hospitalization for medical
      management, may be at risk for CD-related work disability.

PMID- 18076737
TI  - Buried Barrett's epithelium following photodynamic therapy shows reduced crypt
      proliferation and absence of DNA content abnormalities.
AB  - OBJECTIVES: Photodynamic therapy (PDT) is increasingly used for the treatment of
      patients with Barrett's esophagus (BE) with dysplasia or early carcinoma. Post
      PDT, some patients show residual BE either exposed to the luminal surface
      (nonburied) or buried underneath reepithelialized squamous mucosa (buried BE).
      Buried BE may be a serious clinical problem since it can go unnoticed during
      surveillance endoscopies. The neoplastic potential of buried BE is poorly
      understood. The aim of this study was to evaluate the biological characteristics
      of nonburied and buried BE in patients treated with PDT. METHODS: Twelve patients
      selected from a cohort of 52 BE patients who received PDT for high-grade
      dysplasia or intramucosal adenocarcinoma were used for this study because they
      all had both pre- and post-PDT (nonburied), and post-PDT buried, BE biopsies,
      without dysplasia, available for analysis. The biopsies were immunostained for Ki
      67, p53, cyclin D1, bcl-2, TGF-alpha, EGFR, and AMACR. High fidelity DNA
      histograms were obtained by image cytometry analysis of Feulgen stained slides,
      and used to determine peak DNA index (DI), DNA heterogeneity, and 5N exceeding
      rate (5NER). Comparisons were made between pre-PDT nonburied BE and post-PDT
      nonburied and buried BE. RESULTS: Pre-PDT BE showed an elevated Ki-67 crypt
      proliferation rate (43.3%) and p53, bcl-2, TGF-alpha, and EGFR positivity in 8%,
      25%, 75%, and 25% of cases, respectively. Cyclin D1 and AMACR were negative in
      all cases. High fidelity DNA histograms showed mild aneuploidy in 73% of cases.
      Post-PDT buried BE showed a significantly lower Ki-67 crypt proliferation rate
      (29.9%) in comparison to nonburied BE, in both pre- PDT (43.3%) and post-PDT
      (44.4%) biopsies (P < 0.05), but similar rates of positivity for the other
      peptide markers. In contrast to pre-PDT nonburied BE biopsies, high fidelity DNA
      histograms revealed that none of the buried BE (0%), and only 2/9 (11%) nonburied
      BE post-PDT, showed aneuploidy. CONCLUSIONS: Pre-PDT nonburied BE, without
      dysplasia, shows elevated crypt proliferation and mild, but frequent, DNA content
      abnormalities. Post-PDT, nonburied BE shows persistently elevated crypt
      proliferation, but significantly less frequent DNA content abnormalities, whereas
      buried BE shows decreased crypt proliferation and normal DNA content profile.
      These results suggest that post-PDT buried BE may have a lower neoplastic
      potential than pre-PDT BE.

PMID- 18076738
TI  - Drug interactions in inflammatory bowel disease.
AB  - Patients with inflammatory bowel disease (IBD) often require a combination of
      drugs, some of which are taken for many years, to control their disease. Some of
      these drugs have potentially serious side effects, which may be initiated or
      exacerbated by interaction with other agents used to treat IBD. Furthermore,
      patients with IBD may take treatment for other, unrelated conditions. It is
      important for doctors who manage patients with IBD to be aware of, and thereby
      minimize, the dangers presented by such drug interactions. In this review, we
      summarize the common and important interactions of drugs used in patients with
      IBD, including some that may be of therapeutic benefit. Particular attention is
      paid to interactions that occur where both drugs are used to treat IBD.

PMID- 18076739
TI  - Cystic lesions of the pancreas: challenging issues in clinical practice.
AB  - Cystic lesions of the pancreas are being recognized with increasing frequency and
      have become a common finding in clinical practice. Cystic lesions of the pancreas
      display a wide spectrum of histopathology and biologic behavior. Differentiating
      among lesions and choosing an optimal therapy is challenging, and evidence-based
      guidelines for diagnosis, management, and follow-up for cystic lesions of the
      pancreas are needed. This review describes the epidemiology and typical features
      of cystic lesions of the pancreas, including a summary of commonly used
      descriptive terms, as well as the primary issues in the differential diagnosis
      and management of these lesions.

PMID- 18076740
TI  - Improved colorectal adenoma detection with a transparent retractable extension
      device.
AB  - BACKGROUND AND AIMS: Colonoscopy is an excellent but imperfect modality for
      colorectal cancer screening and prevention. We studied the effects of a
      retractable transparent extension device on adenoma detection rate as well as on
      intubation and withdrawal times. METHODS: Colonoscopy with or without the
      transparent retractable extension (TRE) was performed by one endoscopist. A
      subset of patients with colonic adenomas were randomized to repeat colonoscopy
      with or without a TRE device. Adenoma removal was done at the second colonoscopy.
      The principal outcome parameters were the cecal intubation time, withdrawal time,
      and the number, size, and location of adenomas detected. RESULTS: The study was
      done in two parts. First, 835 patients underwent colonoscopy with or without the
      TRE. The patients' demographic characteristics, the indications for colonoscopy,
      the cecal intubation time and withdrawal time, and the proportion of patients
      with adenomas (29.0%vs 24.1%) (P= 0.11) were similar between the two techniques.
      The number of adenomas detected with the TRE was significantly higher than that
      without the extension (205 vs 150) (P= 0.04). Second, 60 patients with adenomas
      found at colonoscopy without the device were randomized to repeat colonoscopy
      within 3 months. Hood-assisted colonoscopy revealed 20% more adenomas than the
      initial procedure compared to a 4% increase without the hood (P= 0.029).
      CONCLUSIONS: Colonoscopy with a TRE device improved the adenoma detection rate
      without affecting intubation and withdrawal times.

PMID- 18076741
TI  - Microsatellites for broodstock management of the Tiger grouper, Epinephelus
      fuscoguttatus.

PMID- 18076742
TI  - The RSPO genes: chromosomal assignment in horse by FISH.

PMID- 18076743
TI  - Identification and verification of QTL associated with growth traits in two
      genetic backgrounds of Barramundi (Lates calcarifer).
AB  - Quantitative trait loci (QTL) affecting growth traits have previously been mapped
      in linkage groups (LG) 2, 3 and 23 of Barramundi (Lates carcalifer), but these
      QTL have not been verified in different genetic backgrounds and environments.
      Here, we report the identification and verification of QTL for growth traits on
      LG2, 3, 10 and 23 in F(1) families constructed using brooders from the Singapore
      Marine Aquaculture Center (MAC) and from wild stocks collected in Thailand
      (THAI). The previously detected QTL for body weight and length linked to marker
      Lca371 on LG2 were confirmed in both the MAC and THAI families, whereas other QTL
      previously mapped to LG3 and 23 were only detected in one of the two families.
      QTL for body weight and length were identified in the MAC family, but not in the
      THAI family, in a region where the insulin-like growth factor 2 (IGF2) and
      tyrosine hydroxylase 1 (TH1) genes are located on LG10. Significant epistatic
      interactions were identified between markers Lca287 on LG2 and IGF2 on LG10 for
      growth trait QTL in the MAC family, but not in the THAI family. Effects of the
      IGF2, TH1 and parvalbumin 1 candidate genes were family-specific. Our results
      indicate that some but not all QTL are family-specific in Barramundi.

PMID- 18076744
TI  - Clonal diversity and genealogical relationships of gibel carp in four hatcheries.
AB  - To conserve and utilize the genetic pool of gynogenetic gibel carp (Carassius
      auratus gibelio), the Fangzheng and Qihe stock hatcheries have been established
      in China. However, little information is available on the amount of genetic
      variation within and between these populations. In this study, clonal diversity
      in 101 fish from these two stock hatcheries and 35 fish from two other hatcheries
      in Wuhan and Pengze respectively was analysed for variation in serum transferrin.
      Thirteen clones were found in Fangzheng and Qihe, of which 12 were novel. Six
      clones were specific to Fangzheng and three specific to Qihe, whereas four were
      shared among the Fangzheng and Qihe fish. To obtain more knowledge on genetic
      diversity and genealogical relationships within gibel carp, the complete
      mitochondrial DNA (mtDNA) control region (approximately 920 bp) was sequenced in
      64 individuals representing all 14 clones identified in the four hatcheries.
      Differences in the mtDNA sequences varied remarkably among hatcheries, with the
      Fangzheng and Qihe lines demonstrating high diversity and Wuhan and Pengze
      showing no variation. The Fangzheng and Qihe lines might represent two distinct
      matrilineal sources. One of the Qihe samples carried the haplotype shared by a
      most widely cultivated Fangzheng clone, indicating that a Fangzheng clone escaped
      from cultivated ponds and moved into the Qihe hatchery. Four Fangzheng samples
      clustered within the lineage formed mainly by Qihe samples, most likely
      reflecting historical gene flow from Qihe to Fangzheng. It is suggested that
      clones in Wuhan originated from Fangzheng, consistent with their introduction
      history, supporting the hypothesis that gibel carp in Pengze were domesticated
      from individuals in the Fangzheng hatchery.

PMID- 18076745
TI  - GEAMM v.1.4: a versatile program for mixed model analysis of gene expression
      data.

PMID- 18076746
TI  - Commentary on Erickson and Wilcox (2006): In defense of gathering evidence on
      changing "dependence" to "addiction" in DSM-V.

PMID- 18076747
TI  - Terminology: impossible dream or tilting at windmills?

PMID- 18076748
TI  - Dependence: fear not.

PMID- 18076750
TI  - The impact of depressive symptoms on alcohol and cigarette consumption following
      treatment for alcohol and nicotine dependence.
AB  - BACKGROUND: Although depression is common among alcohol and tobacco dependent
      patients, its impact on treatment outcomes is not well established. The purpose
      of this study was to examine the impact of depressive symptoms on abstinence from
      tobacco and alcohol after treatment for alcohol dependence and nicotine
      dependence. METHODS: The Timing of Alcohol and Smoking Cessation Study (TASC)
      randomized adults receiving intensive alcohol dependence treatment, who were also
      smokers, to concurrent or delayed smoking cessation treatment. The sample
      consisted of 462 adults who completed depression and substance use (alcohol and
      smoking) assessments at treatment entry and 6, 12, and 18 months posttreatment.
      Longitudinal regression models were used to examine the relationships between
      depression and subsequent abstinence from alcohol and tobacco after baseline
      characteristics, including alcohol and smoking histories, were considered.
      RESULTS: Depressive symptoms were prospectively related to nonabstinence from
      alcohol. Depressive symptoms at the previous assessment increased the odds of
      drinking at the subsequent time point by a factor of 1.67 (95% CI 1.14, 2.43), p
      < 0.01. Depressive symptoms were not significantly related to subsequent
      abstinence from cigarettes. CONCLUSIONS: Depression is an important negative
      predictor of the ability to maintain abstinence from alcohol within the context
      of intensive alcoholism and smoking treatment. It may be important to include
      depression-specific interventions for alcohol and tobacco dependent individuals
      to facilitate successful drinking treatment outcomes.

PMID- 18076751
TI  - Laparoscopic vs. small incision cholecystectomy: Implications for pulmonary
      function and pain. A randomized clinical trial.
AB  - BACKGROUND: Upper abdominal surgery, including laparoscopic cholecystectomy (LC),
      is associated with post-operative pulmonary dysfunction. LC has, by consensus,
      become the treatment of choice for symptomatic cholecystolithiasis. The small
      incision cholecystectomy (SIC), a procedure which does not require a
      pneumoperitoneum threatens to be lost to clinical practice even though there is
      evidence of equality. We hypothesized that the SIC technique should be equal and
      might even be superior to the LC when considering post-operative pulmonary
      function due to the short incision length. METHODS: A single-centre, randomized
      clinical trial was performed including patients scheduled for elective
      cholecystectomy. Pulmonary flow-volume curves were measured pre-operatively, post
      operatively, and at follow up. Blood gas analyses were measured pre-operative, in
      the recovery phase and on post-operative day 1. Anaesthesia, analgesics, and peri
      operative care were standardized by protocol. Post-operatively, patients and
      caregivers were blinded to the procedure. RESULTS: A total of 257 patients were
      analysed. There was one pulmonary complication (pneumonia) in the LC group. In
      both groups, similar reductions of approximately 20% in pulmonary function
      parameters occurred, with complete recovery to pre-operative values. Patients in
      the SIC group consumed more analgesia when compared with the LC group without
      impact on blood gas analysis. Patients converted to a conventional open technique
      showed significant differences in six of the eight parameters in pulmonary
      function tests. CONCLUSION: When evaluated with strict methodology and
      standardization of care, no clinically relevant differences were found between
      SIC and LC regarding pulmonary function. Our results suggest that the popularity
      of the laparoscopic technique cannot be attributed to pulmonary preservation.

PMID- 18076749
TI  - Normal acute behavioral responses to moderate/high dose ethanol in GABAA receptor
      alpha 4 subunit knockout mice.
AB  - BACKGROUND: gamma-Aminobutyric acid type A receptors (GABA(A)-Rs) have been
      implicated in mediating some of the behavioral effects of ethanol (EtOH), but the
      contribution of specific GABA(A)-R subunits is not yet fully understood. The
      GABA(A)-R alpha 4 subunit often partners with beta2/3 and delta subunits to form
      extrasynaptic GABA(A)-Rs that mediate tonic inhibition. Several in vitro studies
      have suggested that these extrasynaptic GABA(A)-Rs may be particularly relevant
      to the intoxicating effects of low doses of EtOH. In alpha 4 subunit knockout
      mice, tonic inhibition was greatly reduced, as were the potentiating effects of
      EtOH. We therefore hypothesized that those behavioral responses to EtOH that are
      mediated by alpha 4-containing GABA(A)-Rs would be diminished in alpha 4 knockout
      mice. METHODS: We investigated behavioral responses to acute administration of
      moderate/high dose EtOH or pentylenetetrazol in alpha 4 subunit knockout mice. We
      compared behavioral responses to EtOH in alpha 4 knockout and wild-type
      littermates in the elevated plus maze (0.0, 1.0 g/kg EtOH), screen test (1.5, 2.0
      g/kg), hypothermia (1.5, 2.0 g/kg), fixed speed rotarod (1.5, 2.0, 2.5 g/kg),
      open field (0.0, 1.0, 2.0 g/kg), radiant tail flick (2.0 g/kg), loss of righting
      reflex (3.5 g/kg), and EtOH metabolism and clearance assays. Sensitivity to
      pentylenetetrazol-induced seizures was also analyzed. RESULTS: No differences
      were observed between alpha 4 knockout mice and wild-type controls in terms of
      the baseline behavior in the absence of EtOH treatment or in the behavioral
      effects of EtOH in the assays tested. In contrast, alpha 4 knockout mice were
      significantly more sensitive to pentylenetetrazol-induced seizures. CONCLUSIONS:
      We conclude that GABA(A)-Rs containing the alpha 4 subunit are not absolutely
      required for the acute behavioral responses to moderate/high dose EtOH that were
      assessed with the elevated plus maze, screen test, hypothermia, fixed speed
      rotarod, open field, radiant tail flick, and loss of right reflex assays. We
      further suggest that these findings are complicated by the demonstrated
      compensatory alterations in synaptic GABA(A)-R EtOH sensitivity and function in
      alpha 4 knockout mice.

PMID- 18076752
TI  - Traumatic avulsion of kidney and spleen into the chest through a ruptured
      diaphragm in a young worker: a case report.
AB  - INTRODUCTION: Rupture of the diaphragm is almost always due to major trauma.
      Diaphragmatic injuries are rare (5-7%), usually secondary to blunt, or more
      rarely to penetrating, thoracic or abdominal trauma. No single investigation
      provides a reliable diagnosis of diaphragmatic rupture when a patient first
      arrives at hospital. Almost 33% are suspected on initial chest x-ray, but the
      percentage is lower in patients who are immediately intubated. Mortality in
      patients with diaphragmatic rupture following blunt abdominal trauma is generally
      associated with coexistent vascular and visceral injuries that could be rapidly
      fatal. It's mandatory that the right diagnosis is reached as soon as possible
      given that mortality is influenced by the time elapsing between trauma and
      diagnosis. CASE PRESENTATION: A 35-year-old worker was hit by a heavy object
      while working in the factory. He was transferred immediately to our emergency
      room. Chest x-ray showed massive left hemothorax without any additional signs to
      suggest diaphragmatic injury. It was decided to perform immediate surgical
      exploration before further radiological examination. During surgery, the right
      kidney and liver appeared normal, but the left kidney and spleen were not found
      in their anatomical position. The left hemidiaphragm had a10-cm oblique posterior
      tear. The left kidney was found lacerated in the left side of the chest,
      separated completely from its vascular pedicle and ureter, along with the entire
      spleen which was also separated from its vascular tree. CONCLUSION: The avulsion
      of both kidney and spleen following abdominal trauma is uncommon and survival
      depends on prompt diagnosis and treatment.

PMID- 18076753
TI  - Synthesis of densely functionalized enantiopure indolizidines by ring-closing
      metathesis (RCM) of hydroxylamines from carbohydrate-derived nitrones.
AB  - BACKGROUND: Indolizidine alkaloids widely occur in nature and display interesting
      biological activity. This is the reason for which their total synthesis as well
      as the synthesis of non-natural analogues still attracts the attention of many
      research groups. To establish new straightforward accesses to these molecules is
      therefore highly desirable. RESULTS: The ring closing metathesis (RCM) of
      enantiopure hydroxylamines bearing suitable unsaturated groups cleanly afforded
      piperidine derivatives in good yields. Further cyclization and deprotection of
      the hydroxy groups gave novel highly functionalized indolizidines. The synthesis
      of a pyrroloazepine analogue is also described. CONCLUSION: We have developed a
      new straightforward methodology for the synthesis of densely functionalized
      indolizidines and pyrroloazepine analogues in 6 steps and 30-60% overall yields
      from enantiopure hydroxylamines obtained straightforwardly from carbohydrate
      derived nitrones.

PMID- 18076754
TI  - Part 1. Reduction of S-alkyl-thionocarbonates and related compounds in the
      presence of trialkylboranes/air.
AB  - A new, mild, and environment friendly process for the reduction of S-alkyl
      thionocarbonates, iodides and related compounds to the corresponding hydrocarbons
      at room temperature with good to excellent yields is described. This method uses
      a trialkylborane in excess (Et3B or Bu3B) and air.

PMID- 18076755
TI  - Part 2. Mechanistic aspects of the reduction of S-alkyl-thionocarbonates in the
      presence of triethylborane and air.
AB  - Experiments conducted with deuterated compounds demonstrated that during the
      reduction of S-alkylxanthates with triethylborane, the hydrogen atom transferred
      has several competing origins. Hydrogen abstraction from water (or an alcohol) is
      the most favourable route.

PMID- 18076756
TI  - Platelet-derived growth factor receptor-beta, carrying the activating mutation
      D849N, accelerates the establishment of B16 melanoma.
AB  - BACKGROUND: Platelet-derived growth factor (PDGF)-BB and PDGF receptor (PDGFR)
      beta are mainly expressed in the developing vasculature, where PDGF-BB is
      produced by endothelial cells and PDGFR-beta is expressed by mural cells,
      including pericytes. PDGF-BB is produced by most types of solid tumors, and PDGF
      receptor signaling participates in various processes, including autocrine
      stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and
      stimulation of tumor angiogenesis. Furthermore, PDGF-BB-producing tumors are
      characterized by increased pericyte abundance and accelerated tumor growth. Thus,
      there is a growing interest in the development of tumor treatment strategies by
      blocking PDGF/PDGFR function. We have recently generated a mouse model carrying
      an activated PDGFR-beta by replacing the highly conserved aspartic acid residue
      (D) 849 in the activating loop with asparagine (N). This allowed us to
      investigate, in an orthotopic tumor model, the role of increased stromal PDGFR
      beta signaling in tumor-stroma interactions. METHODS: B16 melanoma cells lacking
      PDGFR-beta expression and either mock-transfected or engineered to express PDGF
      BB, were injected alone or in combination with matrigel into mice carrying the
      activated PDGFR-beta (D849N) and into wild type mice. The tumor growth rate was
      followed and the vessel status of tumors, i.e. total vessel area/tumor, average
      vessel surface and pericyte density of vessels, was analyzed after resection.
      RESULTS: Tumors grown in mice carrying an activated PDGFR-beta were established
      earlier than those in wild-type mice. In this early phase, the total vessel area
      and the average vessel surface were higher in tumors grown in mice carrying the
      activated PDGFR-beta (D849N) compared to wild-type mice, whereas we did not find
      a significant difference in the number of tumor vessels and the pericyte
      abundance around tumor vessels between wild type and mutant mice. At later phases
      of tumor progression, no significant difference in tumor growth rate was observed
      between wild type mice and mutant mice, although the pericyte coverage was higher
      around tumor vessels from mutant mice. CONCLUSION: Our findings suggest that the
      activated PDGFR-beta (D849N) in the host animal increased the total vessel area
      and the average vessel surface even in PDGF-negative tumors, resulting in a
      shorter lag phase during tumor establishment.

PMID- 18076757
TI  - Norwegian farmers' vigilance in reporting sheep showing scrapie-associated signs.
AB  - BACKGROUND: Scrapie is a chronic neurodegenerative disease affecting small
      ruminants and belongs to the transmissible spongiform encephalopathies. Scrapie
      is considered a serious animal disease and it has been notifiable in Norway since
      1965. The clinical signs of scrapie might be vague and the farmers, if familiar
      with the signs of scrapie, are often in the best position for detecting scrapie
      suspects. In 2002, an anonymous questionnaire survey was conducted in order to
      assess Norwegian sheep farmers' vigilance of scrapie. RESULTS: Although the
      potential detection of a scrapie-positive animal would lead to the destruction of
      the sheep flock concerned, almost all the farmers (97 %) expressed their
      willingness to report scrapie suspects. This was most certainly dependent on the
      Government taking the economic responsibility for the control programme as nearly
      all the farmers responded that this was an important condition. Listeriosis is
      relatively common disease in Norwegian sheep and a differential diagnosis for
      scrapie. In a multinomial logistic regression the reporting behaviour for non
      recovering listeriosis cases, used as a measurement of willingness to report
      scrapie, was examined. The reporting of non-recovering listeriosis cases
      increased as the knowledge of scrapie-associated signs increased, and the
      reporting behaviour was dependent on both economic and non-economic values.
      CONCLUSION: The results indicate that in 2002 almost all sheep farmers showed
      willingness to report any scrapie suspects. Nevertheless there is an
      underreporting of scrapie suspects and the farmers' awareness and hence their
      vigilance of scrapie could be improved. Furthermore, the results suggest that to
      ensure the farmers' compliance to control programmes for serious infectious
      diseases, the farmers' concerns of non-economic as well as economic values should
      be considered.

PMID- 18076758
TI  - Strongyloides stercoralis infection in a Finnish kennel.
AB  - BACKGROUND: Intestinal threadworm Strongyloides stercoralis is a parasite of dog,
      cat and primates that occurs worldwide being most prevalent in tropical and
      subtropical countries. The adult parasitic worm is about 2 mm long and slender.
      It possesses both parasitic and free-living lifecycles. The parasitic worms are
      females. Strongyloides stercoralis infects the host via percutaneous, peroral or
      transmammary transmission in addition to autoinfection. Clinical disease varies
      from inapparent to severe enteritis and pneumonia. The diagnosis is based on
      demonstration of larvae in fresh faeces, which is best made by Baermann
      technique. CASE PRESENTATION: Strongyloides stercoralis infection was diagnosed
      in autopsy in a 10-week-old puppy born and raised in a Finnish kennel. Prior to
      its sudden death, the puppy had suffered from gastrointestinal disturbance for
      three weeks. Subsequent sampling of the dogs in the kennel revealed that three
      adult dogs in the kennel were also infected. CONCLUSION: The present case shows
      that S. stercoralis can complete its life cycle and cause disease in dogs also in
      Northern Europe. Infection can be maintained also in a temperate climate and may
      become a chronic problem in a kennel environment. Infection may be underdiagnosed
      as Baermann technique is not routinely performed in small animal practice.

PMID- 18076759
TI  - Male urine signals social rank in the Mozambique tilapia (Oreochromis
      mossambicus).
AB  - BACKGROUND: The urine of freshwater fish species investigated so far acts as a
      vehicle for reproductive pheromones affecting the behaviour and physiology of the
      opposite sex. However, the role of urinary pheromones in intra-sexual competition
      has received less attention. This is particularly relevant in lek-breeding
      species, such as the Mozambique tilapia (Oreochromis mossambicus), where males
      establish dominance hierarchies and there is the possibility for chemical
      communication in the modulation of aggression among males. To investigate whether
      males use urine during aggressive interactions, we measured urination frequency
      of dye-injected males during paired interactions between size-matched males.
      Furthermore, we assessed urinary volume stored in the bladder of males in a
      stable social hierarchy and the olfactory potency of their urine by recording of
      the electro-olfactogram. RESULTS: Males released urine in pulses of short
      duration (about one second) and markedly increased urination frequency during
      aggressive behaviour, but did not release urine whilst submissive. In the stable
      hierarchy, subordinate males stored less urine than males of higher social rank;
      the olfactory potency of the urine was positively correlated with the rank of the
      male donor. CONCLUSION: Dominant males store urine and use it as a vehicle for
      odorants actively released during aggressive disputes. The olfactory potency of
      the urine is positively correlated with the social status of the male. We suggest
      that males actively advertise their dominant status through urinary odorants
      which may act as a 'dominance' pheromone to modulate aggression in rivals,
      thereby contributing to social stability within the lek.

PMID- 18076760
TI  - Models predicting the growth response to growth hormone treatment in short
      children independent of GH status, birth size and gestational age.
AB  - BACKGROUND: Mathematical models can be used to predict individual growth
      responses to growth hormone (GH) therapy. The aim of this study was to construct
      and validate high-precision models to predict the growth response to GH treatment
      of short children, independent of their GH status, birth size and gestational
      age. As the GH doses are included, these models can be used to individualize
      treatment. METHODS: Growth data from 415 short prepubertal children were used to
      construct models for predicting the growth response during the first years of GH
      therapy. The performance of the models was validated with data from a separate
      cohort of 112 children using the same inclusion criteria. RESULTS: Using only
      auxological data, the model had a standard error of the residuals (SDres), of
      0.23 SDS. The model was improved when endocrine data (GHmax profile, IGF-I and
      leptin) collected before starting GH treatment were included. Inclusion of these
      data resulted in a decrease of the SDres to 0.15 SDS (corresponding to 1.1 cm in
      a 3-year-old child and 1.6 cm in a 7-year old). Validation of these models with a
      separate cohort, showed similar SDres for both types of models. Preterm children
      were not included in the Model group, but predictions for this group were within
      the expected range. CONCLUSION: These prediction models can with high accuracy be
      used to identify short children who will benefit from GH treatment. They are
      clinically useful as they are constructed using data from short children with a
      broad range of GH secretory status, birth size and gestational age.

PMID- 18076761
TI  - In silico and in vitro comparative analysis to select, validate and test SNPs for
      human identification.
AB  - BACKGROUND: The recent advances in human genetics have recently provided new
      insights into phenotypic variation and genome variability. Current forensic DNA
      techniques involve the search for genetic similarities and differences between
      biological samples. Consequently the selection of ideal genomic biomarkers for
      human identification is crucial in order to ensure the highest stability and
      reproducibility of results. RESULTS: In the present study, we selected and
      validated 24 SNPs which are useful in human identification in 1,040 unrelated
      samples originating from three different populations (Italian, Benin Gulf and
      Mongolian). A Rigorous in silico selection of these markers provided a list of
      SNPs with very constant frequencies across the populations tested as demonstrated
      by the Fst values. Furthermore, these SNPs also showed a high specificity for the
      human genome (only 5 SNPs gave positive results when amplified in non-human DNA).
      CONCLUSION: Comparison between in silico and in vitro analysis showed that
      current SNPs databases can efficiently improve and facilitate the selection of
      markers because most of the analyses performed (Fst, r2, heterozigosity) in more
      than 1,000 samples confirmed available population data.

PMID- 18076763
TI  - Evolution of allostery in the cyclic nucleotide binding module.
AB  - BACKGROUND: The cyclic nucleotide binding (CNB) domain regulates signaling
      pathways in both eukaryotes and prokaryotes. In this study, we analyze the
      evolutionary information embedded in genomic sequences to explore the diversity
      of signaling through the CNB domain and also how the CNB domain elicits a
      cellular response upon binding to cAMP. RESULTS: Identification and
      classification of CNB domains in Global Ocean Sampling and other protein
      sequences reveals that they typically are fused to a wide variety of functional
      domains. CNB domains have undergone major sequence variation during evolution. In
      particular, the sequence motif that anchors the cAMP phosphate (termed the PBC
      motif) is strikingly different in some families. This variation may contribute to
      ligand specificity inasmuch as members of the prokaryotic cooA family, for
      example, harbor a CNB domain that contains a non-canonical PBC motif and that
      binds a heme ligand in the cAMP binding pocket. Statistical comparison of the
      functional constraints imposed on the canonical and non-canonical PBC containing
      sequences reveals that a key arginine, which coordinates with the cAMP phosphate,
      has co-evolved with a glycine in a distal beta2-beta3 loop that allosterically
      couples cAMP binding to distal regulatory sites. CONCLUSION: Our analysis
      suggests that CNB domains have evolved as a scaffold to sense a wide variety of
      second messenger signals. Based on sequence, structural and biochemical data, we
      propose a mechanism for allosteric regulation by CNB domains.

PMID- 18076762
TI  - Delayed functional expression of neuronal chemokine receptors following focal
      nerve demyelination in the rat: a mechanism for the development of chronic
      sensitization of peripheral nociceptors.
AB  - BACKGROUND: Animal and clinical studies have revealed that focal peripheral nerve
      axon demyelination is accompanied by nociceptive pain behavior. C-C and C-X-C
      chemokines and their receptors have been strongly implicated in demyelinating
      polyneuropathies and persistent pain syndromes. Herein, we studied the degree to
      which chronic nociceptive pain behavior is correlated with the neuronal
      expression of chemokines and their receptors following unilateral
      lysophosphatidylcholine (LPC)-induced focal demyelination of the sciatic nerve in
      rats. RESULTS: Focal nerve demyelination increased behavioral reflex
      responsiveness to mechanical stimuli between postoperative day (POD) 3 and POD28
      in both the hindpaw ipsilateral and contralateral to the nerve injury. This
      behavior was accompanied by a bilateral increase in the numbers of primary
      sensory neurons expressing the chemokine receptors CCR2, CCR5, and CXCR4 by
      POD14, with no change in the pattern of CXCR3 expression. Significant increases
      in the numbers of neurons expressing the chemokines monocyte chemoattractant
      protein-1 (MCP-1/CCL2), Regulated on Activation, Normal T Expressed and Secreted
      (RANTES/CCL5) and interferon gamma-inducing protein-10 (IP-10/CXCL10) were also
      evident following nerve injury, although neuronal expression pattern of stromal
      cell derived factor-1alpha (SDF1/CXCL12) did not change. Functional studies
      demonstrated that acutely dissociated sensory neurons derived from LPC-injured
      animals responded with increased [Ca2+]i following exposure to MCP-1, IP-10, SDF1
      and RANTES on POD 14 and 28, but these responses were largely absent by POD35. On
      days 14 and 28, rats received either saline or a CCR2 receptor antagonist isomer
      (CCR2 RA-[R]) or its inactive enantiomer (CCR2 RA-[S]) by intraperitoneal (i.p.)
      injection. CCR2 RA-[R] treatment of nerve-injured rats produced stereospecific
      bilateral reversal of tactile hyperalgesia. CONCLUSION: These results suggest
      that the presence of chemokine signaling by both injured and adjacent, uninjured
      sensory neurons is correlated with the maintenance phase of a persistent pain
      state, suggesting that chemokine receptor antagonists may be an important
      therapeutic intervention for chronic pain.

PMID- 18076764
TI  - Prevalence and patterns of soft tissue metastasis: detection with true whole-body
      F-18 FDG PET/CT.
AB  - BACKGROUND: The aim of this retrospective study was to report the prevalence and
      patterns of soft tissue (ST) metastasis detected with true whole-body (TWB) F-18
      FDG PET/CT acquired from the top of the skull through the bottom of the feet and
      to compare such findings to that of the typically acquired skull-base to upper
      thigh, thus limited whole-body (LWB) field of view (FOV). METHODS: TWB FDG-PET/CT
      scans were performed in 500 consecutive cancer patients. Suspected ST metastasis
      was verified by correlation with surgical pathology, other imaging modalities, or
      clinical follow-up. RESULTS: Nine out of 500 patients (1.8 %) had ST metastasis
      with a prevalence of 4/41 (9.8%) for melanoma, 2/60 (3.3%) for lung carcinoma,
      2/88 (2.3%) for lymphoma and 1/13 (77%) for esophageal cancer. Those nine
      patients had a total of 41 ST lesions: 22 lesions within and 19 outside of LWB
      FOV. Of those 41 lesions, 19 (46%) were subcutaneous and 22 (54%) were muscular
      lesions. The presence of ST metastasis neither changed the staging nor the
      treatment in any of these patients. However, the ST lesions provided a biopsy
      site in 4 of the 9 patients (44%). Seven out of nine studied patients died of
      their disease within 1-22 months after ST metastasis was diagnosed. CONCLUSION:
      The detection of ST metastasis may have prognostic implications, provide more
      accessible biopsy sites and help avoid invasive procedures. A LWB scanning may
      underestimate the true extent of ST metastasis since a significant percentage of
      ST metastasis (46%) occurred outside the typical LWB FOV.

PMID- 18076765
TI  - On the analysis of glycomics mass spectrometry data via the regularized area
      under the ROC curve.
AB  - BACKGROUND: Novel molecular and statistical methods are in rising demand for
      disease diagnosis and prognosis with the help of recent advanced biotechnology.
      High-resolution mass spectrometry (MS) is one of those biotechnologies that are
      highly promising to improve health outcome. Previous literatures have identified
      some proteomics biomarkers that can distinguish healthy patients from cancer
      patients using MS data. In this paper, an MS study is demonstrated which uses
      glycomics to identify ovarian cancer. Glycomics is the study of glycans and
      glycoproteins. The glycans on the proteins may deviate between a cancer cell and
      a normal cell and may be visible in the blood. High-resolution MS has been
      applied to measure relative abundances of potential glycan biomarkers in human
      serum. Multiple potential glycan biomarkers are measured in MS spectra. With the
      objection of maximizing the empirical area under the ROC curve (AUC), an analysis
      method was considered which combines potential glycan biomarkers for the
      diagnosis of cancer. RESULTS: Maximizing the empirical AUC of glycomics MS data
      is a large-dimensional optimization problem. The technical difficulty is that the
      empirical AUC function is not continuous. Instead, it is in fact an empirical 0-1
      loss function with a large number of linear predictors. An approach was
      investigated that regularizes the area under the ROC curve while replacing the 0
      1 loss function with a smooth surrogate function. The constrained threshold
      gradient descent regularization algorithm was applied, where the regularization
      parameters were chosen by the cross-validation method, and the confidence
      intervals of the regression parameters were estimated by the bootstrap method.
      The method is called TGDR-AUC algorithm. The properties of the approach were
      studied through a numerical simulation study, which incorporates the positive
      values of mass spectrometry data with the correlations between measurements
      within person. The simulation proved asymptotic properties that estimated AUC
      approaches the true AUC. Finally, mass spectrometry data of serum glycan for
      ovarian cancer diagnosis was analyzed. The optimal combination based on TGDR-AUC
      algorithm yields plausible result and the detected biomarkers are confirmed based
      on biological evidence. CONCLUSION: The TGDR-AUC algorithm relaxes the normality
      and independence assumptions from previous literatures. In addition to its
      flexibility and easy interpretability, the algorithm yields good performance in
      combining potential biomarkers and is computationally feasible. Thus, the
      approach of TGDR-AUC is a plausible algorithm to classify disease status on the
      basis of multiple biomarkers.

PMID- 18076766
TI  - Phase II study of intraperitoneal recombinant interleukin-12 (rhIL-12) in
      patients with peritoneal carcinomatosis (residual disease < 1 cm) associated with
      ovarian cancer or primary peritoneal carcinoma.
AB  - BACKGROUND: Pharmacokinetic advantages of intraperitoneal (IP) rhIL-12, tumor
      response to IP delivery of other cytokines as well as its potential anti
      angiogenic effect provided the rationale for further evaluation of IPrhIL-12 in
      patients with persistent ovarian or peritoneal carcinoma. METHODS: A phase 2
      multi-institutional trial (NCI Study #2251) of IP rIL-12 (300 nanogram/Kg weekly)
      was conducted in patients with ovarian carcinoma or primary peritoneal carcinoma.
      Patients treated with primary therapy for ovarian cancer who had no
      extraabdominal/parenchymal disease or bulky peritoneal disease were eligible.
      Four to 8 weeks from last chemotherapy, eligible patients underwent a
      laparotomy/laparoscopy. Patients with residual disease < or = 1 cm were
      registered for the treatment phase 2-5 weeks post surgery. The effect of IP rIL
      12 on the expression of TNFalpha , INFalpha , IL-10, IP-10, IL-8, FGF, VEGF was
      also studied. RESULTS: Thirty-four patients were registered for the first
      screening phase of the study. Median age was 56.6 years (range: 31-71); 12
      completed the second phase and were evaluable for response/toxicity. Performance
      scores of IL-12 treated patients were 0 (11 pts) and 1 (1 pt). There were no
      treatment related deaths, peritonitis or significant catheter related
      complications. Toxicities included grade 4 neutropenia (1), grade 3 fatigue (4),
      headache (2), myalgia (2), non-neutropenic fever (1), drug fever (1), back pain
      (1), and dizziness (1). The best response observed was SD. Two patients had SD
      and 9 had PD, and 1 was evaluable for toxicity only. Peritoneal fluid cytokine
      measurements demonstrated a > or = 3 fold relative increase post-rhIL-12: IFN
      gamma, 5/5 pts; TNF-alpha , 1/5; IL-10, 4/5; IL-8, 5/5; and VEGF, 3/5. IP10
      levels were increased in 5/5 patients. Cytokine response profiles suggest either
      NK or T-cell mediated effects of IP rhIL-12. Cytokine/chemokine results also
      suggest a pleiotropic response since proteins with potential for either anti
      tumor (IFN-gamma , IP-10) or pro-tumor growth effects (VEGF, IL-8) were detected.
      CONCLUSION: IP IL-12 can safely be administered at this dose and schedule to
      patients after first line chemotherapy for ovarian/peritoneal carcinoma. The
      maximum response was stable disease. Future IP therapies with rhIL-12 will
      require better understanding and control of pleiotropic effects of IL-12.

PMID- 18076767
TI  - Apoptosis is not the major death mechanism induced by celecoxib on rheumatoid
      arthritis synovial fibroblasts.
AB  - Synovial hyperplasia in rheumatoid arthritis (RA) has been associated with
      apoptosis deficiency of RA fibroblast-like synoviocytes (FLSs). Celecoxib is a
      non-steroidal anti-inflammatory drug that has been demonstrated to induce
      apoptosis in some cellular systems. We have therefore examined the dose- and time
      dependent effects of celecoxib on RA FLS viability. Treatment of RA FLSs with
      celecoxib for 24 hours reduced their viability in a dose-dependent manner.
      Analysis of celecoxib-treated RA FLSs for their content of apoptotic and necrotic
      cells by Annexin V staining and TO-PRO-3 uptake displayed only few apoptotic
      cells. Caspase 3, a key mediator of apoptosis, was not activated in celecoxib
      treated RA FLSs, and the presence of specific caspase 3 or pan-caspase inhibitors
      did not affect celecoxib-induced cell death. Moreover, we could not detect other
      signs of apoptosis, such as cleavage of poly(ADP-ribose) polymerase, caspase 8 or
      9, or DNA fragmentation. We therefore conclude that apoptosis is not the major
      death pathway in celecoxib-treated RA FLSs.

PMID- 18076769
TI  - Unravelling the molecular control of calvarial suture fusion in children with
      craniosynostosis.
AB  - BACKGROUND: Craniosynostosis, the premature fusion of calvarial sutures, is a
      common craniofacial abnormality. Causative mutations in more than 10 genes have
      been identified, involving fibroblast growth factor, transforming growth factor
      beta, and Eph/ephrin signalling pathways. Mutations affect each human calvarial
      suture (coronal, sagittal, metopic, and lambdoid) differently, suggesting
      different gene expression patterns exist in each human suture. To better
      understand the molecular control of human suture morphogenesis we used microarray
      analysis to identify genes differentially expressed during suture fusion in
      children with craniosynostosis. Expression differences were also analysed between
      each unfused suture type, between sutures from syndromic and non-syndromic
      craniosynostosis patients, and between unfused sutures from individuals with and
      without craniosynostosis. RESULTS: We identified genes with increased expression
      in unfused sutures compared to fusing/fused sutures that may be pivotal to the
      maintenance of suture patency or in controlling early osteoblast differentiation
      (i.e. RBP4, GPC3, C1QTNF3, IL11RA, PTN, POSTN). In addition, we have identified
      genes with increased expression in fusing/fused suture tissue that we suggest
      could have a role in premature suture fusion (i.e. WIF1, ANXA3, CYFIP2). Proteins
      of two of these genes, glypican 3 and retinol binding protein 4, were
      investigated by immunohistochemistry and localised to the suture mesenchyme and
      osteogenic fronts of developing human calvaria, respectively, suggesting novel
      roles for these proteins in the maintenance of suture patency or in controlling
      early osteoblast differentiation. We show that there is limited difference in
      whole genome expression between sutures isolated from patients with syndromic and
      non-syndromic craniosynostosis and confirmed this by quantitative RT-PCR.
      Furthermore, distinct expression profiles for each unfused suture type were
      noted, with the metopic suture being most disparate. Finally, although calvarial
      bones are generally thought to grow without a cartilage precursor, we show
      histologically and by identification of cartilage-specific gene expression that
      cartilage may be involved in the morphogenesis of lambdoid and posterior sagittal
      sutures. CONCLUSION: This study has provided further insight into the complex
      signalling network which controls human calvarial suture morphogenesis and
      craniosynostosis. Identified genes are candidates for targeted therapeutic
      development and to screen for craniosynostosis-causing mutations.

PMID- 18076770
TI  - Parental mental illness and fatal birth defects in a national birth cohort.
AB  - BACKGROUND: Few large studies describe links between maternal mental illness and
      risk of major birth defect in offspring. Evidence is sparser still for how
      effects vary between maternal diagnoses and no previous study has assessed risk
      with paternal illnesses. METHOD: A population-based birth cohort was created by
      linking Danish national registers. We identified all singleton live births during
      1973-1998 (n=1.45 m), all parental psychiatric admissions from 1969 onwards, and
      all fatal birth defects until 1 January 1999. Linkage and case ascertainment were
      almost complete. Relative risks were estimated using Poisson regression. RESULTS:
      Risk of fatal birth defect was elevated in relation to history of any maternal
      admission and also with affective disorders specifically, although the strongest
      effect found was with maternal schizophrenia. The rate was more than doubled in
      this group compared to the general population [relative risk (RR) 2.34, 95%
      confidence interval (CI) 1.45-3.77], which also represented a significant excess
      risk compared with all other admitted maternal disorders (p=0.018). Risk of death
      from causes other than birth defect was no higher with schizophrenia than with
      other maternal conditions. There was no elevation in risk of fatal birth defect
      if the father was admitted with schizophrenia or any other psychiatric diagnosis.
      CONCLUSIONS: There are many possible explanations for a higher risk of fatal
      birth defect with maternal schizophrenia and affective disorder. These include
      genetic effects directly linked with maternal illness, lifestyle factors (diet,
      smoking, alcohol and drugs), poor antenatal care, psychotropic medication
      toxicity, and gene-environment interactions. Further research is needed to
      elucidate the causal mechanisms.

PMID- 18076768
TI  - Asn 362 in gp120 contributes to enhanced fusogenicity by CCR5-restricted HIV-1
      envelope glycoprotein variants from patients with AIDS.
AB  - BACKGROUND: CCR5-restricted (R5) human immunodeficiency virus type 1 (HIV-1)
      variants cause CD4+ T-cell loss in the majority of individuals who progress to
      AIDS, but mechanisms underlying the pathogenicity of R5 strains are poorly
      understood. To better understand envelope glycoprotein (Env) determinants
      contributing to pathogenicity of R5 viruses, we characterized 37 full-length R5
      Envs from cross-sectional and longitudinal R5 viruses isolated from blood of
      patients with asymptomatic infection or AIDS, referred to as pre-AIDS (PA) and
      AIDS (A) R5 Envs, respectively. RESULTS: Compared to PA-R5 Envs, A-R5 Envs had
      enhanced fusogenicity in quantitative cell-cell fusion assays, and reduced
      sensitivity to inhibition by the fusion inhibitor T-20. Sequence analysis
      identified the presence of Asn 362 (N362), a potential N-linked glycosylation
      site immediately N-terminal to CD4-binding site (CD4bs) residues in the C3 region
      of gp120, more frequently in A-R5 Envs than PA-R5 Envs. N362 was associated with
      enhanced fusogenicity, faster entry kinetics, and increased sensitivity of Env
      pseudotyped reporter viruses to neutralization by the CD4bs-directed Env mAb
      IgG1b12. Mutagenesis studies showed N362 contributes to enhanced fusogenicity of
      most A-R5 Envs. Molecular models indicate N362 is located adjacent to the CD4
      binding loop of gp120, and suggest N362 may enhance fusogenicity by promoting
      greater exposure of the CD4bs and/or stabilizing the CD4-bound Env structure.
      CONCLUSION: Enhanced fusogenicity is a phenotype of the A-R5 Envs studied, which
      was associated with the presence of N362, enhanced HIV-1 entry kinetics and
      increased CD4bs exposure in gp120. N362 contributes to fusogenicity of R5 Envs in
      a strain dependent manner. Our studies suggest enhanced fusogenicity of A-R5 Envs
      may contribute to CD4+ T-cell loss in subjects who progress to AIDS whilst
      harbouring R5 HIV-1 variants. N362 may contribute to this effect in some
      individuals.

PMID- 18076771
TI  - Hearing a voice in the noise: auditory hallucinations and speech perception.
AB  - BACKGROUND: It has recently been suggested that auditory hallucinations are the
      result of a criterion shift when deciding whether or not a meaningful signal has
      emerged. The approach proposes that a liberal criterion may result in increased
      false-positive identifications, without additional perceptual deficit. To test
      this hypothesis, we devised a speech discrimination task and used signal
      detection theory (SDT) to investigate the underlying cognitive mechanisms.
      METHOD: Schizophrenia patients with and without auditory hallucinations and a
      healthy control group completed a speech discrimination task. They had to decide
      whether a particular spoken word was identical to a previously presented speech
      stimulus, embedded in noise. SDT was used on the accuracy data to calculate a
      measure of perceptual sensitivity (Az) and a measure of response bias (beta).
      Thresholds for the perception of simple tones were determined. RESULTS: Compared
      to healthy controls, perceptual thresholds were higher and perceptual sensitivity
      in the speech task was lower in both patient groups. However, hallucinating
      patients showed increased sensitivity to speech stimuli compared to non
      hallucinating patients. In addition, we found some evidence of a positive
      response bias in hallucinating patients, indicating a tendency to readily accept
      that a certain stimulus had been presented. CONCLUSIONS: Within the context of
      schizophrenia, patients with auditory hallucinations show enhanced sensitivity to
      speech stimuli, combined with a liberal criterion for deciding that a perceived
      event is an actual stimulus.

PMID- 18076772
TI  - Reproduction in Strongyloides (Nematoda): a life between sex and parthenogenesis.
AB  - Nematodes of the genus Strongyloides parasitize the small intestines of
      vertebrates. In addition to a parasitic life-cycle, which is generally considered
      to be parthenogenetic, Strongyloides can also have a facultative, free-living
      generation involving male and female worms. The purpose of the present article
      was to review the literature on the modes of reproduction, the routes of
      development in the two generations of Strongyloides, discuss the controversial
      opinions in the literature regarding these aspects and point to new opportunities
      for addressing key questions in relation to the biology of reproduction of
      members of the genus employing genetic and genomic tools.

PMID- 18076773
TI  - Characterization of highly concentrated serum lectins in spotted halibut Verasper
      variegatus.
AB  - Mannose-binding lectins were purified from flatfish spotted halibut (Verasper
      variegatus) serum. These lectins, which we named VVL (Verasper variegatus lectin)
      alpha (approximately 33 kDa) and VVL-beta (approximately 30 kDa) (VVLs), under
      non-reducing SDS-PAGE, were surprisingly highly concentrated in serum (1.92+/
      0.55 mg/ml; n=5), compared with other serum lectins. Both VVLs are heterodimers
      comprised of 2 types of subunit via inter-subunit disulfide bonds, and one
      subunit of VVL-alpha has a N-linked sugar chain. Based on N-terminal amino acid
      sequences, the nucleotide sequences of one subunit of VVL cDNAs were determined
      by 3'- and 5'-rapid amplification of the cDNA ends. The full-length VVL subunit
      cDNAs contained 489 bp, encoding an open reading frame of 163 amino acids. We
      found that VVLs bind to an approximately 8 kDa ciliary surface glycoprotein (a
      putative agglutination/immobilization antigen that we reported previously) of the
      fish parasite Neobenedenia girellae, and agglutinate this parasite in vitro.

PMID- 18076774
TI  - The parasitoid complex of Parthenolecanium corni Bouche in the city of Tbilisi
      and its surroundings and comparison with some other European countries.
AB  - The European fruit lecanium (EFL), Parthenolecanium corni Bouche (Hemiptera:
      Coccoidea), is a common and harmful soft scale, which attacks Fraxinus oxycarpa
      Willd. and other ornamental and orchard plants in Tbilisi, Georgia. This study
      investigates the phenology, degree of plant damage and effect of parasitoids on
      this scale in Tbilisi, a densely populated area. We present data on the 32
      species of chalcidoid parasitoids recorded from EFL in Georgia and south-eastern
      Europe. The scale is heavily parasitized in Tbilisi, but we did not find any
      variation in seasonal abundance. The most common parasitoid of EFL was
      Blastothrix longipennis (Hymenoptera: Encyrtidae).

PMID- 18076775
TI  - A multiplex PCR assay for the simultaneous identification of three mealybug
      species (Hemiptera: Pseudococcidae).
AB  - Molecular species identification is becoming more wide-spread in diagnostics and
      ecological studies, particularly with regard to insects for which morphological
      identification is difficult or time-consuming. In this study, we describe the
      development and application of a single-step multiplex PCR for the identification
      of three mealybug species (Hemiptera: Pseudococcidae) associated with grapevine
      in South Africa: Planococcus ficus (vine mealybug), Planococcus citri (citrus
      mealybug) and Pseudococcus longispinus (longtailed mealybug). Mealybugs are pests
      on many commercial crops, including grapevine, in which they transmit viral
      diseases. Morphological identification of mealybug species is usually time
      consuming, requires a high level of taxonomic expertise and usually only adult
      females can be identified. The single-step multiplex PCR developed here, based on
      the mitochondrial cytochrome c oxidase subunit 1 (CO I) gene, is rapid, reliable,
      sensitive, accurate and simple. The entire identification protocol (including DNA
      extraction, PCR and electrophoresis) can be completed in approximately four
      hours. Successful DNA extraction from laboratory and unparasitized field
      collected individuals stored in absolute ethanol was 97%. Specimens from which
      DNA could be extracted were always correctly identified (100% accuracy). The
      technique developed is simple enough to be implemented in any molecular
      laboratory. The principles described here can be extended to any organism for
      which rapid, reliable identification is needed.

PMID- 18076776
TI  - The influence of natural enemies on wing induction in Aphis fabae and Megoura
      viciae (Hemiptera: Aphididae).
AB  - Previous studies have shown that the aphid species, Aphis fabae Scopoli and
      Megoura viciae Buckton, do not produce winged offspring in the presence of
      natural enemies, in contrast to results for the pea aphid (Acyrthosiphon pisum
      (Harris)) and the cotton aphid (Aphis gossypii Glover); but these studies did not
      involve exposing aphids directly to natural enemies. We exposed colonies of both
      A. fabae and M. viciae to foraging lacewing (Chrysoperla carnea (Stephens))
      larvae and found that the predators did not induce winged morphs among offspring
      compared to unexposed controls. Colonies of A. fabae responded to an increase in
      aphid density with increasing winged morph production, while such response was
      not found for M. viciae. We suggest that different aphid species differ in their
      susceptibility to natural enemy attack, as well as in their sensitivity to
      contact.

PMID- 18076777
TI  - Mating activity of Bactrocera cacuminata (Hering) (Diptera: Tephritidae) on its
      larval host plant Solanum mauritianum Scopoli in southeast Queensland.
AB  - A detailed study was conducted on the mating behaviour of Bactrocera cacuminata
      (Hering) (Diptera: Tephritidae) in nature. Plant tissues from Solanum mauritianum
      Scopoli, the primary larval host for B. cacuminata, were also analysed for methyl
      eugenol content. In the field, over a 15 month period, 44,171 observations of
      adult B. cacuminata individuals were made including 1109 mating pairs on S.
      mauritianum. Calling behaviour consisting of wing fanning and anus beating by
      males was also consistently observed on the underside of leaves of S. mauritianum
      after sunset. Female flies that arrived into these groups of 10-15 calling males
      were mated and often remained coupled until dawn. No methyl eugenol was detected
      from the analysis of leaves, flowers and fruits of S. mauritianum. Thus, B.
      cacuminata does not need to aggregate at sites where methyl eugenol is present
      and the hypothesis that this chemical plays a role in the selection of mating
      sites by B. cacuminata is not supported by the current study. It is concluded
      that S. mauritianum is the primary site of mating for B. cacuminata in nature and
      that the concept that the larval host plant is the centre of activity for dacine
      fruit flies remains robust, being fully supported by the results of this study.

PMID- 18076778
TI  - Comparison of five allopatric fruit fly parasitoid populations (Psyttalia
      species) (Hymenoptera: Braconidae) from coffee fields using morphometric and
      molecular methods.
AB  - Morphometric studies of five allopatric parasitoid populations (genus Psyttalia
      Walker) from coffee plantations in Cameroon (Nkolbisson), Ghana (Tafo) and Kenya
      (Rurima, Ruiru and Shimba Hills) and one non-coffee population (from Muhaka,
      Kenya) were compared with individuals of Psyttalia concolor (Szepligeti), a
      species released in several biological control programmes in the Mediterranean
      Region since the 20th Century. Analyses of wing vein measurements showed the
      second submarginal cell of the fore wing and its adjoining veins had the heaviest
      principal component weights and served as the main contributing variables in the
      diagnostic differentiation of the populations. Two populations (Rurima and Ruiru)
      were found to be the closest to each other and with the strongest phenetic
      affinity toward P. concolor (and forming one cluster). Populations from Shimba
      Hills (of unknown identity), Nkolbisson (P. perproximus (Silvestri)) and Tafo
      formed a second cluster and were separated from P. concolor. Comparison using
      amplified fragment length polymorphism (AFLP) also showed the Shimba, Nkolbisson
      and Tafo populations forming a cluster in a dendrogram generated from their
      genetic distances, with the Shimba and Tafo populations placed as the most
      closely related species. Based on consistent morphological similarities,
      morphometric and ecological data coupled with the genetic evidence from AFLP
      data, the Shimba population is suggested as belonging to the P. perproximus group
      and, thus, represents a new occurrence record in Kenya. Our results also support
      earlier conclusion from cross mating data that populations from Rurima and Ruiru
      belong to the Psyttalia concolor species-group.

PMID- 18076779
TI  - Effects of Helicoverpa armigera (Noctuidae, Lepidoptera) host stages on some
      developmental parameters of the uniparental endoparasitoid Meteorus pulchricornis
      (Braconidae, Hymenoptera).
AB  - A single choice test was performed to examine developmental strategies in the
      uniparental endoparasitoid Meteorus pulchricornis and its host, the cotton
      bollworm Helicoverpa armigera. The results support the dome-shaped model in which
      the fitness functions are 'dome-shaped' relative to size (and age) of host at
      parasitism. Older and, hence, larger host larvae were simply not better hosts for
      the developing parasitoids. Although parasitoid size (measured as cocoon weight
      and adult hind tibia length) was positively correlated with host instars at
      parasitism, parasitoids developing in larger hosts (L5 and L6) suffered much
      higher mortality than conspecifics developing in smaller hosts (L2-L4).
      Furthermore, egg-to-adult development time in M. pulchricornis was significantly
      longer in older host larvae (L4-L6) than in the younger. Performance of M.
      pulchricornis, as indicated by fitness-related traits, strongly suggests that the
      L3 host is the most suitable for survival, growth and development of the
      parasitoid, followed by both L2 and L4 hosts; whereas, L1, L5 and L6 are the
      least favourable hosts. The oviposition tendency of M. pulchricornis, represented
      by parasitism level, was not perfectly consistent with the performance of the
      offspring; L2-L4 hosts, although with the same parasitism level, had offspring
      parasitoids with differences in fitness-related performance. Larval development
      in Helicoverpa armigera was usually suspended, but occasionally advanced, in the
      final instar.

PMID- 18076780
TI  - Clonal turnover of MACE-carrying peach-potato aphids (Myzus persicae (Sulzer),
      Homoptera: Aphididae) colonizing Scotland.
AB  - Peach-potato aphids, Myzus persicae (Sulzer), collected in Scotland in the years
      1995 and 2002-2004 were characterized using four microsatellite loci and three
      insecticide resistance mechanisms. From 868 samples, 14 multilocus genotypes were
      defined (designated clones A-N). Five of these (denoted A, B, H, M and N) carried
      modified acetylcholinesterase (MACE) resistance, the most recent resistance
      mechanism to have evolved in M. persicae. The current paper shows that the
      continued presence of MACE aphids is due to turnover, as clones A and B were
      replaced in field samples by clones H, M and N in later seasons. Thus,
      insecticide-resistant populations in Scotland can be attributed to multiple waves
      of rapid clone colonisations and not to the continued presence of stable
      resistant clones or mutation or sexual recombination in local populations. The
      MACE clones carried varying levels of the other insecticide resistance
      mechanisms, kdr and esterase. The presence of these mechanisms could alter the
      clones success in the field depending on insecticide spraying (positive
      selection) and resistance fitness costs (negative selection).

PMID- 18076781
TI  - Kampimodromus aberrans (Acari: Phytoseiidae) from the USA: morphological and
      molecular assessment of its density.
AB  - Morphological measurements and a mitochondrial molecular marker (COI) were used
      to identity specimens reported as Kampimodromus aberrans on hazelnut in the USA.
      Several species and populations of this genus were studied to assist with
      identification. Both data types showed that specimens from the USA differed from
      K. aberrans from other regions. USA specimens seem to belong to the same species
      as Kampimodromus specimens from France on hazelnut. These mites were
      morphologically similar to Kampimodromus coryli and K. corylosus, which according
      to the original descriptions, are distinguished by the presence or absence of a
      tooth on the movable digit of the chelicera, with K. coryli having one tooth and
      K. corylosus none. As chelicerae of Kampimodromus from hazelnut in the USA and
      France are toothless, they are assigned to the species K. corylosus. Studies
      showed that morphological characters traditionally used to identify Kampimodromus
      species, such as setal length, are of less value than other characters that are
      difficult to observe, such as the numbers of solenostomes and the presence of
      teeth on the movable digit of the chelicerae. Some synonyms are discussed.

PMID- 18076782
TI  - Molecular characterization of Gonatocerus tuberculifemur (Ogloblin) (Hymenoptera:
      Mymaridae), a prospective Homalodisca vitripennis (Germar) (Hemiptera:
      Cicadellidae) biological control candidate agent from South America: divergent
      clades.
AB  - We genetically characterized the prospective South American egg parasitoid
      candidate, Gonatocerus tuberculifemur, of the glassy-winged sharpshooter (GWSS),
      Homalodisca vitripennis, for a neoclassical biological control program in
      California. Two molecular methods, inter-simple sequence repeat-polymerase chain
      reaction DNA fingerprinting and a phylogeographic approach inferred from the
      mitochondrial cytochrome oxidase subunit I gene (COI), were utilized. Five
      geographic populations from South America were analyzed; in addition, a
      phylogenetic analysis was performed with several named and one unnamed
      Gonatocerus species using the COI gene. DNA fingerprinting demonstrated a fixed
      geographic banding pattern difference in the population from San Rafael, Mendoza
      Province, Argentina. The COI analysis uncovered haplotype or geographic structure
      in G. tuberculifemur. A neighbour-joining distance (NJ) and a single most
      parsimonious tree (MP) clustered the populations into two well-supported distinct
      clades with strong bootstrap values (97-99% and 92-99%, respectively) with
      populations from San Rafael clustering into clade 2 and the rest of the
      populations clustering into clade 1. No haplotype sharing was observed between
      individuals from the two clades. Phylogenetic analyses performed by NJ and MP
      methods with 15 Gonatocerus species confirmed species boundaries and again
      uncovered two distinct clades in G. tuberculifemur with strong bootstrap support
      (95-100% and 68-100%, respectively). However, the NJ tree supported the
      morphologically defined relationships better than the MP tree. The molecular
      evidence in the present study is suggestive of a species level divergence.
      Because G. tuberculifemur is under consideration as a potential biological
      control agent for GWSS in California, understanding cryptic variation in this
      species is critical.

PMID- 18076783
TI  - A radar study of emigratory flight and layer formation by insects at dawn over
      southern Britain.
AB  - Radar observations have consistently shown that high-altitude migratory flight in
      insects generally occurs after mass take-off at dusk or after take-off over a
      more extended period during the day (in association with the growth of
      atmospheric convection). In this paper, we focus on a less-studied third category
      of emigration - the 'dawn take-off' - as recorded by insect-monitoring radars
      during the summer months in southern England. In particular, we describe
      occasions when dawn emigrants formed notable layer concentrations centred at
      altitudes ranging from ca. 240 m to 700 m above ground, very probably due to the
      insects responding to local temperature maxima in the atmosphere, such as the
      tops of inversions. After persisting for several hours through the early morning,
      the layers eventually merged into the insect activity building up later in the
      morning (from 06.00-08.00 h onwards) in conjunction with the development of
      daytime convection. The species forming the dawn layers have not been positively
      identified, but their masses lay predominantly in the 16-32 mg range, and they
      evidently formed a fauna quite distinct from that in flight during the previous
      night. The displacement and common orientation (mutual alignment) characteristics
      of the migrants are described.

PMID- 18076784
TI  - Seasonal and annual genotypic variation and the effect of climate on population
      genetic structure of the cereal aphid Sitobion avenae in northern France.
AB  - Changes in the genetic structure and genotypic variation of the aphid Sitobion
      avenae collected from cereal crops in northern France were examined by analysing
      variation at five microsatellite loci across several years and seasons. Little
      regional and temporal differentiation was detected, as shown by very low FST
      among populations. Repeated genotypes, significant heterozygote deficits,
      positive FIS values and frequent linkage disequilibria were found in nearly all
      samples, suggesting an overall pattern of reproductive mode variation in S.
      avenae populations. In addition, samples from Brittany (Bretagne) showed greater
      signs of asexual reproduction than those from the north of France, indicating a
      trend toward increasing sexuality northward. These patterns of reproductive
      variation in S. avenae are consistent with theoretical models of selection of
      aphid reproductive modes by climate. Contrasting with little changes in allelic
      frequencies, genotypic composition varied substantially in time and, to a lesser
      extent, in space. An important part of changes in genotypic arrays was due to the
      variation in frequency distribution of common genotypes, i.e. those that were
      found at several instances in the samples. Genotypic composition was also shown
      to vary according to climate, as genotypic diversity in spring was significantly
      correlated with the severity of the previous winter and autumn. We propose that
      the genetic homogeneity among S. avenae populations shown here across large
      temporal and spatial scales is the result of two forces: (i) migration conferred
      by high dispersal capabilities, and (ii) selection over millions of hectares of
      cereals (mostly wheat) bred from a narrow genetic base.

PMID- 18076785
TI  - Spatial and temporal patterns of carabid activity-density in cereals do not
      explain levels of predation on weed seeds.
AB  - Seed predation is an important component of seed mortality of weeds in agro
      ecosystems, but the agronomic use and management of this natural weed suppression
      is hampered by a lack of insight in the underlying ecological processes. In this
      paper, we investigate whether and how spatial and temporal variation in activity
      density of granivorous ground beetles (Coleoptera: Carabidae) results in a
      corresponding pattern of seed predation. Activity-density of carabids was
      measured by using pitfall traps in two organic winter wheat fields from March to
      July 2004. Predation of seeds (Capsella bursa-pastoris, Lamium amplexicaule, Poa
      annua and Stellaria media) was assessed using seed cards at the same sites and
      times. As measured by pitfall traps, carabids were the dominant group of insects
      that had access to the seed cards. In the field, predation of the four different
      species of seed was in the order: C. bursa-pastoris>P. annua>S. media>L.
      amplexicaule; and this order of preference was confirmed in the laboratory using
      the dominant species of carabid. On average, seed predation was higher in the
      field interior compared to the edge, whereas catches of carabids were highest
      near the edge. Weeks with elevated seed predation did not concur with high
      activity-density of carabids. Thus, patterns of spatial and temporal variation in
      seed predation were not matched by similar patterns in the abundance of
      granivorous carabid beetles. The lack of correspondence is ascribed to effects of
      confounding factors, such as weather, the background density of seeds, the
      composition of the carabid community, and the phenology and physiological state
      of the beetles. Our results show that differences in seed loss among weed species
      may be predicted from laboratory trials on preference. However, predator activity
      density, as measured in pitfall traps, is an insufficient predictor of seed
      predation over time and space within a field.

PMID- 18076786
TI  - Characterization of the M918T sodium channel gene mutation associated with strong
      resistance to pyrethroid insecticides in the peach-potato aphid, Myzus persicae
      (Sulzer).
AB  - Recent advances in the characterisation of insect sodium channel gene sequences
      have identified a small number of point mutations within the channel protein that
      are implicated in conferring target-site resistance to pyrethroid insecticides
      (so-called knockdown resistance or kdr). The L1014F (leucine-to-phenylalanine)
      mutation located in the centre of segment 6 of the domain II region (IIS6) of the
      sodium channel (the so-called kdr trait) has been detected in the peach-potato
      aphid, Myzus persicae (Sulzer), and is considered to be the primary cause of
      pyrethroid resistance in this species. Here we report on the characterisation of
      a second mutation, M918T (methione-to-threonine), within the nearby IIS4-S5
      intracellular linker (the so-called super-kdr trait) in a field clone also
      possessing L1014F, with both mutations present in heterozygous form. The
      resistance phenotype of M. persicae clones possessing various combinations of
      L1014F and M918T to a wide range of pyrethroids (both Type I and II) was assessed
      in leaf-dip bioassays and to lambda-cyhalothrin applied at up to ten times the
      recommended field rate as foliar sprays to aphids feeding on whole plants.
      Bioassay results demonstrated that presence of both mutations was associated with
      extreme resistance to all the pyrethroids tested relative to aphids lacking the
      mutations. Furthermore, this resistance well exceeded that shown by aphids that
      were homozygous for L1014F but lacking M918T. However, pre-treatment with
      piperonyl butoxide in the leaf-dip bioassays failed to suppress pyrethroid
      resistance in aphids carrying one or both of the mutations. The relevance of
      these findings for monitoring and managing pyrethroid resistance in M. persicae
      populations in the field is discussed.

PMID- 18076787
TI  - [Role of Rho GTPase in inhibiting metastatic ability of human prostate cancer
      cell line PC-3 by omega-3 polyunsaturated fatty acid].
AB  - BACKGROUND & OBJECTIVE: Recently, researches refer to the influence of
      polyunsaturated fatty acid (PUFA) on cancer initiation and progression had been
      highly concerned. This study was to investigate the effects of 2 kinds of omega-3
      PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the
      metastatic ability of human prostate cancer cell line PC-3, and explore the role
      of Rho GTPase in inhibiting cancer metastasis by omega-3 PUFA. METHODS: MTT assay
      was used to determine the effects of omega-3 PUFA on the proliferation of PC-3
      cells. Adhesion assay, invasion assay, and migration assay were used to observe
      the effects of omega-3 PUFA on the metastatic ability of PC-3 cells. Western blot
      was used to observe the effects of omega-3 PUFA on the expression of RhoA, Rac1,
      Rac2, and Cdc42 proteins in PC-3 cells. Laser confocal microscopy was used to
      investigate the effect of omega-3 PUFA on the reorganization of the
      microfilaments and microtubules marked by immunofluorescent cytochemistry
      technology. RESULTS: Both EPA and DHA inhibited the proliferation of PC-3 cells,
      and the proliferation inhibition rate increased along with the increase of the
      concentration and treatment time. When treated with 60 mumol/L EPA or DHA for 48
      h, the abilities of adhesion, invasion and migration of PC-3 cells were inhibited
      (P<0.05). omega-3 PUFA significantly suppressed the expression of Rac1, Rac2 and
      Cdc42 proteins (P<0.05), influenced the distribution and structure of
      sytoskeletons. CONCLUSION: omega-3 PUFA could inhibit the metastatic ability of
      PC-3 cells through down-regulating the expression of Rho GTPase and inhibiting
      the cytoskeleton reorganization.

PMID- 18076788
TI  - [Preparation of docetaxel liposomes and their pharmacokinetics in rabbits].
AB  - BACKGROUND & OBJECTIVE: Docetaxel is used to treat non-small cell lung cancer,
      breast cancer and ovarian cancer. It is indissolvable and the solvent containing
      polysorbate-80 and 13% solution of ethanol is used for injections. Its clinical
      application is limited because of frequent severe hypersensitive responses. This
      study was to prepare docetaxel (DOC) liposomes and investigate their
      pharmacokinetics in rabbits after intravenous administration. METHODS: DOC
      liposomes, with or without modification of polyethylene glycol (PEG), were
      prepared by thin-film ultrasonic dispersion method. The entrapment efficiency and
      mean diameter of the liposomes were measured. After intravenous administration in
      rabbits, plasma DOC concentration was detected by solid phase extraction high
      performance liquid chromatography (SPE-HPLC). The pharmacokinetic parameters were
      calculated and analyzed by 3p87 pharmacokinetic program. RESULTS: The entrapment
      efficiency of DOC liposomes was above 75%. The mean diameter was about 150 nm.
      The half-life of distribution (T(1/2alpha)) were (0.17+/-0.04) h for market
      docetaxel injection (M-DOC), (0.31+/-0.11) h for common DOC liposome (L-DOC), and
      (0.32+/-0.06) h for PEG-2000-modified DOC long circulating liposome (PEG-DOC
      LCL); the half-life of clearance (T(1/2beta)) were (8.54+/-1.05), (11.18+/-1.33),
      and (10.51+/-1.13) h, respectively; the apparent volume of distribution (V(d))
      were (13.66+/-3.62), (8.65+/-1.11), and (6.31+/-0.55) L, respectively; the area
      under the concentration-time curve from 0 to 24 h (AUC(0-->24)) were (13.45+/
      2.44), (22.83+/-3.57), and (29.31+/-5.96) mg x (h x L)(-1), respectively; the
      area under the concentration-time curve from 0 to infinity h (AUC(0-->infinity))
      were (15.07+/-2.76), (28.70+/-4.95), and (36.95+/-9.13) mg x (h x L)(-1),
      respectively; the clearance (CL) were (1.10+/-0.18), (0.54+/-0.08), and (0.42+/
      0.07) L/h, respectively. CONCLUSION: The thin-film prepared DOC liposomes have
      high entrapment efficiency and small particle size. Both liposomes, especially
      PEG-DOC-LCL, can raise AUC and prolong the resident time of drugs in the blood
      circulating system.

PMID- 18076789
TI  - [Effects of interleukin-12 transfection on proliferation of ovarian cancer SKOV3
      cells in vitro and in vivo].
AB  - BACKGROUND & OBJECTIVE: The incidence, recurrence rate, and metastasis rate of
      malignant ovarian tumors are high. Interleukin-12 (IL-12) has antitumor effect.
      This study was to investigate the effects of IL-12 on the proliferation of human
      ovarian carcinoma SKOV3 cells in vitro and in vivo. METHODS: The plasmid
      containing mouse IL-12 gene was transfected into SKOV3 cells (SKOV3/IL-12). Blank
      plasmid-transfected SKOV3 cells (SKOV3/neo) and untransfected SKOV3 cells were
      used as controls. The expression of IL-12 protein was detected by ELISA. The
      proliferation inhibition rate and population doubling time (PDT) of SKOV3 cells
      were evaluated by MTT assay. SKOV3/IL-12, SKOV3/neo and SKOV3 cells were
      inoculated in nude mice subcutaneously. Tumor growth was recorded. The serum
      levels of IL-12 and interferon-gamma (IFN-gamma) in mice was detected by ELISA.
      The expression of vascular endothelial growth factor (VEGF) and IFN-gamma
      inducible protein 10 (IP-10), and microvessel density (MVD) in tumor tissues was
      detected by immunohistochemistry. RESULTS: After transfection, the protein level
      of IL-12 was significantly higher in SKOV3/IL-12 cells than in SKOV3/neo and
      SKOV3 cells [(473.0+/-38.0) pg/ml vs. (16.0+/-1.3) pg/ml and (16.0+/-1.2) pg/ml
      at 48 h, (522.0+/-32.0) pg/ml vs. (18.0+/-1.6) pg/ml and (17.0+/-1.4) pg/ml at 60
      h, P<0.01]. The proliferation inhibition rate of SKOV3/IL-12 cells was
      significantly higher than those of SKOV3/neo and SKOV3 cells (63.7% vs. 0% and
      0%, P<0.01). The PDT was significantly longer in SKOV3/IL-12 cells than in
      SKOV3/neo and SKOV3 cells [(45.8+/-2.7) h vs. (27.6+/-2.2) h and (28.2+/-2.1) h,
      P<0.01]. In nude mice, the tumor formation rate of SKOV3/IL-12 cells was lower
      than those of control cells (5/8 vs. 8/8 and 8/8)u the tumor formation time was
      significantly longer in SKOV3/IL-12 group than in SKOV3/neo group and SKOV3 group
      [(15.0+/-5.0) days vs. (7.9+/-3.2) days and (7.8+/-2.4) days, P<0.01]. The volume
      and weight of tumors and the body weight of mice were significantly lower in
      SKOV3/IL-12 group than in SKOV3/neo group and SKOV3 group (P<0.01). The serum
      levels of IL-12 and IFN-gamma were significantly higher in SKOV3/IL-12 group than
      in SKOV3/neo group and SKOV3 group (P<0.01). The positive rate of VEGF and MVD
      were significantly lower and the positive rate of IP-10 was higher in SKOV3/IL-12
      group than in SKOV3/neo group and SKOV3 group (P<0.01). CONCLUSIONS: Transfection
      of IL-12 can inhibit the proliferation and suppress the tumorigenic ability of
      SKOV3 cells. IL-12 can promote IFN-gamma to induce IP-10 production, thereafter,
      inhibit neovascularization in tumors.

PMID- 18076790
TI  - [Cytotoxic effect of epidermal growth factor receptor tyrosine kinase inhibitor
      ZD1839 in combination with oxaliplatin on lung cancer cell line A549].
AB  - BACKGROUND & OBJECTIVE: ZD1839, a selective epidermal growth factor receptor
      tyrosine kinase inhibitor (EGFR-TKI), has clinical antitumor activity, but its
      efficacy is low. This study was to assess the effects of ZD1839 in combination
      with oxaliplatin on lung adenocarcinoma cell line A549, and to provide pre
      clinical evidence for optimizing the schedule of oxaliplatin combined with
      ZD1839. METHODS: Chou and Talalay method was used to analyze the combination
      effects of sequencing ZD1839 and oxaliplatin on A549 cells. Cell cycle
      distribution and cell apoptosis were analyzed by flow cytometry. The effects of
      oxaliplatin combined with ZD1839 on the proliferation of A549 cells in nude mice
      were also evaluated. RESULTS: Sequential oxaliplatin followed by ZD1839 produced
      synergistic effect, with a combination index (CI) of 0.51+/-0.01. In contrast,
      ZD1839 followed by oxaliplatin exhibited antagonist effect, with a CI of 1.56+/
      0.03. Compared with other sequences, oxaliplatin followed by ZD1839 induced more
      cells being arrested in G(2/M) phase (37.9%, P<0.05); the apoptosis rate was
      22.3%. The inhibition rate of tumor growth in nude mice was 58.9% when treated
      with oxaliplatin followed by ZD1839, 52.4% when treated with oxaliplatin and
      ZD1839 for 24 h and followed by ZD1839 for additional 48 h, and 30.6% when
      treated with ZD1839 followed by oxaliplatin. CONCLUSION: Sequential oxaliplatin
      followed by ZD1839 has the maximal inhibitory effect on the proliferation of A549
      cells.

PMID- 18076791
TI  - [Inhibitory effect of arsenic trioxide on proliferation of human hepatocellular
      carcinoma cell line SMMC-7721 and the mechanism].
AB  - BACKGROUND & OBJECTIVE: Arsenic trioxide (As(2)O(3)) is a new drug used to treat
      solid tumors. However, the mechanism is still unclear. This study was to
      investigate the effects of As(2)O(3) on the proliferation of human hepatocellular
      carcinoma (HCC) cell line SMMC-7721, and to explore the mechanisms. METHODS: When
      treated with 0-8 micromol/L As(2)O(3) for 96 h, the survival rate of SMMC-7721
      cells was determined by WST-8 assay. When treated with 2 micromol/L As(2)O(3) for
      72 h, the expression of P27(kip1) and c-Jun activation domain-binding protein 1
      (JAB1) in SMMC-7721 cells were detected at different time points by Western blot,
      the subcellular localization of P27(kip1) and JAB1 was detected by subcellular
      fractionation and immunofluorescent staining. RESULTS: As(2)O(3) significantly
      inhibited the proliferation of SMMC-7721 cells. The 50% inhibition concentration
      (IC50) of As(2)O(3) to SMMC-7721 cells was (1.81+/-0.41) micromol/L at 96 h. When
      SMMC-7721 cells were treated with 2 mumol/L As(2)O(3) for 12 h, the expression of
      JAB1 was down-regulated and that of P27kip1 was up-regulated. Furthermore,
      P27(kip1) and JAB1 proteins were translocated from the cytoplasm into nuclei when
      cells were exposed to 2 micromol/L As(2)O(3) for 12 h and 24 h, respectively. The
      nuclear accumulation of both proteins was also observed under fluorescence
      microscope after treatment of 2 micromol/L As(2)O(3). CONCLUSION: As(2)O(3)
      attenuates JAB1 expression, thereby disturbs the location and expression of
      P27(kip1), and may participate in regulating the proliferation of SMMC-7721 cells
      through interfering with the function of P27(kip1).

PMID- 18076792
TI  - [Effects of flavonoids with different structures on proliferation of leukemia
      cell line HL-60].
AB  - BACKGROUND & OBJECTIVE: Flavonoids, with some beneficial biological activities,
      exist extensively in foods and herbal products. This study was to evaluate the
      effects of 23 flavonoids on the proliferation of leukemia cell line HL-60, and
      elucidate the structure-activity relationship (SAR). METHODS: HL-60 cells were
      treated with 23 flavonoids with high purity and definite structure. Cell
      proliferation was detected by MTT assay. The 50% inhibition concentrations (IC50)
      of the 23 flavonoids were calculated. The effects of particular structures on
      IC50 were evaluated. RESULTS: Most of the 23 flavonoids inhibited the
      proliferation of HL-60 cells distinctly, and the effects were enhanced along with
      increasing concentrations. However, the intensity of their effects were
      different, which were arranged from strong to weak as follows:3,6
      dihydroxyflavone > luteolin > geraldol > 2'-hydroxyflavanone > apigenin > 3,7
      dihydroxyflavone > myricetin > fisetin > baicalein > quercetin > flavanone >
      chrysin > galangin > 4'-hydroxyflavanone > 6-hydroxyflavone > genistein > flavone
      >7-hydroxyflavone > daidzein > hesperetin > naringenin. The 2,3-double bond in
      ring C, appropriate hydroxyls, ring B attached at position 2, hydroxyls in
      position 3, ortho-substituting hydroxyls in ring B were related to enhanced
      inhibitory effects of flavonoids on the proliferation of HL-60 cells, while the
      lack of 2,3-double bond, deficiency or redundancy of hydroxyl groups, hydroxyl
      group in position 5, 7 or meta-substituting hydroxyls in ring B, isoflavone
      structure were related to reduced inhibitory effects of flavonoids. CONCLUSION:
      The 2,3-double bond in ring C, appropriate hydroxyls, ring B attached at position
      2, hydroxyls in position 3, ortho-substituting hydroxyls in ring B may be key
      structural requirements of flavonoids for potent cytotoxicity to HL-60 cells.

PMID- 18076793
TI  - [Effects of melittin on growth and angiogenesis of human hepatocellular carcinoma
      BEL-7402 cell xenografts in nude mice].
AB  - BACKGROUND & OBJECTIVE: Melittin has antitumor effects on osteosarcoma, leukemia,
      and cervical cancer in vitro. Our previous experiments showed that melittin could
      inhibit proliferation and induce apoptosis of human hepatocellular carcinoma BEL
      7402 cells. This study was to examine the effects of melittin on the growth and
      angiogenesis of BEL-7402 cell xenografts in nude mice. METHODS: The xenografts
      derived from BEL-7402 cells were established in BALB/C nude mice. Inoculated mice
      were randomly divided into normal saline (NS, 10 ml/kg) group, positive control
      (thalidomide, TLD, 200 mg/kg) group, low dose melittin (40 microg/kg) group,
      moderate dose melittin (60 microg/kg) group and high dose melittin (80 microg/kg)
      group. Tumor volume was measured. Tumor tissue was observed under microscope.
      Microvessel density (MVD) and the expression of vascular endothelial growth
      factor (VEGF), basic fibroblast growth factor (bFGF) and nuclear factor kappaB
      (NF-kappaB) were detected by SABC immunohistochemistry. The mRNA levels of VEGF
      and bFGF were analyzed by real-time fluorescent quantitative polymerase chain
      reaction. RESULTS: The relative tumor volume (V/V0) and MVD were significantly
      lower in low, moderate and high dose melittin groups than in NS group (4.42+/
      0.58, 3.47+/-0.97, and 3.06+/-1.23 vs. 9.06+/-1.45, P<0.01; 11.33+/-1.86, 9.17+/
      1.17, and 6.67+/-1.21 vs. 16.50+/-2.35, P<0.01). Tumor tissue necrosis was
      observed in melittin-treated groups and tumor vessels were destroyed by melittin.
      The positive expression indexes of VEGF (2.59+/-0.27, 2.61+/-0.17, 1.55+/-0.22
      vs. 3.80+/-0.60, P<0.01), bFGF (2.45+/-0.78, 2.27+/-0.36, 2.10+/-0.27 vs. 4.43+/
      0.34, P<0.01) and NF-kappaB (2.79+/-0.29, 2.71+/-0.66, 2.26+/-0.56 vs. 4.98+/
      0.63, P<0.01) were significantly lower in low, moderate and high dose melittin
      groups than in NS group. The mRNA levels of VEGF and bFGF were also significantly
      lower in melittin-treated groups than in NS group. CONCLUSIONS: Melittin could
      inhibit the growth of BEL-7402 cell xenografts in nude mice. The down-regulation
      of VEGF, b-FGF and NF-kappaB expression and the inhibition of angiogenesis might
      play key roles in the antitumor effect of melittin.

PMID- 18076794
TI  - [Effects of sodium valproate on proliferation and apoptosis of human
      myelodysplastic syndromes cell line MUTZ-1].
AB  - BACKGROUND & OBJECTIVE: Myelodysplastic syndromes (MDS) are heterogeneous
      disorders with the expansion of malignant clones. No satisfactory treatment for
      MDS is available. Sodium valproate (VPA) can inhibit the proliferation of tumor
      cells by inducing G(0)/G(1) phase arrest and cell apoptosis. This study was to
      investigate the effects of VPA on the proliferation of MDS cell line MUTZ-1, and
      explore possible mechanisms. METHODS: MUTZ-1 cells were treated with VPA. Cell
      proliferation was determined by MTT assay. Cell morphology was observed under
      microscope and transmission electron microscope. Cell apoptosis and cell cycle
      were analyzed by flow cytometry (FCM). The expression of p21(WAF1) (cyclin
      dependent kinase inhibitor) was detected by reverse transcription-polymerase
      chain reaction (RT-PCR) and Western blot. RESULTS: VPA inhibited the
      proliferation of MUTZ-1 cells in concentration-and time-dependent manners. When
      treated with 4 mmol/L VPA for 72 h, typical apoptotic morphologic features
      appeared in MUTZ-1 cells: condensation of cells and nuclear chromatin,
      disintegration of nuclear chromatin, and apoptotic bodies were observed under
      microscope; aggregation and margination of apoptotic nuclear chromatin, cytoplasm
      condensation, and irregular chromatin masses were observed under transmission
      electron microscope. The apoptosis rate was significantly higher in the cells
      treated with 1, 2, and 4 mmol/L VPA for 72 h than in untreated cells [(3.14+/
      0.87)%, (14.90+/-1.04)% and (22.46+/-1.74)% vs. (0.99+/-0.35)%, P<0.05]. After
      treatment of VPA, cell cycle was arrested obviously at G0/G1 phase (P<0.05)u the
      mRNA and protein levels of p21(WAF1) were up-regulated in MUTZ-1 cells (P<0.05).
      CONCLUSIONS: VPA could induce G(0)/G(1) phase arrest, inhibit the proliferation
      and induce the apoptosis of MUTZ-1 cells in vitro. The mechanism may be
      associated with the up-regulation of p21(WAF1).

PMID- 18076795
TI  - [Effect of gefitinib on radiosensitivity of gastric cancer cell lines].
AB  - BACKGROUND & OBJECTIVE: Epidermal growth factor receptor (EGFR) is expressed in
      most human epithelial cancers and is involved in the development of cancer cell
      resistance to irradiation. We used gefitinib, a selective EGFR tyrosine kinase
      inhibitor (EGFR-TKI), to investigate its effects and mechanisms in enhancing the
      radiosensitivity of human gastric cancer cell lines in vitro. METHODS: The
      expression of EGFR protein in 7 human gastric cell lines (MKN45, SGC7901, SNU-1,
      N87, AGS, SNU-16, and KATO-III) was determined by Western blot, in which 2 cell
      lines with high expression of EGFR were selected for additional test. The
      inhibitory effect of gefitinib on cell proliferation was measured by MTT assay.
      Cell survival was determined by clonogenic assay, and then the radiosensitivity
      parameters were calculated. The effects of gefitinib in combination with
      radiation on cell apoptosis and cell cycle distribution were analyzed by flow
      cytometry. RESULTS: Of the 7 gastric cancer cell lines, the expression of EGFR in
      MKN45 and SGC7901 cells were the highest. The 50% inhibition concentrations
      (IC(50)) of gefitinib were 0.4 mmol/L for MKN45 cells and 0.8 mmol/L for SGC7901
      cells. Cell survival was significantly decreased with the elevation of gefitinib
      concentration or radiation dose (P<0.05). When treated with 0.1x and 0.2 x IC(50)
      of gefitinib, the radiosensitization enhancement ratios (SER) of MKN45 cells were
      1.102 and 1.154, and those of SGC7901 cells were 1.092 and 1.176, respectively.
      Either gefitinib or radiation induced cell apoptosis, reduced the percentage of
      cells at S phase and increased the percentage of cells at G(2)/M phase (P<0.01).
      CONCLUSIONS: Gefitinib followed by radiation could increase the radiosensitivity
      of MKN45 and SGC7901 cells with high expression of EGFR and inhibit cell
      proliferation, induce apoptosis, and alter cell phase distribution. Gefitinib
      could be a radiation sensitizer for gastric tumors with high expression of EGFR.

PMID- 18076796
TI  - [Pathogen spectrum and drug resistance of spit samples from cancer patients].
AB  - BACKGROUND & OBJECTIVE: Some cancer patients were not died of cancer, but died of
      infection after operation, chemotherapy, radiotherapy, or interventional
      treatment. This study was to investigate the pathogen spectrum and drug
      resistance of spit samples from cancer patients. METHODS: The pathogen spectrum
      and drug resistance of 955 positive spit samples from cancer patients were
      analyzed with WHONET-5 statistical software. RESULTS: The detection rates were
      43.3% for fungus (mainly included C.albicans), 31.2% for Gram-positive coccus
      (mainly included coagulase-negative Staphylococcus), and 25.5% for Gram-negative
      bacillus (mainly included P.aeruginosa and K.pneumonia). Drug sensitivity test
      showed that fungus was sensitive to amphotericin B, but resistant against
      categorical azoles; Gram-positive coccus was highly sensitive to vancomycin, but
      highly resistant against oxacillin, penicillin and erythromycin; Gram-negative
      bacillus was highly sensitive to impanel, but highly resistant against the first
      and second generations of cephalosporin such as ampicillin and piperacillin.
      CONCLUSIONS: The pathogen spectrum of cancer patients with nosocomial infection
      mainly includes fungus, Gram-positive coccus, and Gram-negative coccus. Treating
      cancer patients with antibiotics should be based on drug sensitivity test.

PMID- 18076797
TI  - [Efficacy of modified B-NHL-BFM-90 protocol on Burkitt's lymphoma in Chinese
      children and adolescents].
AB  - BACKGROUND & OBJECTIVE: Burkitt's lymphoma is an aggressive non-Hodgkin's
      lymphoma (NHL) and often involves bone marrow and central nerve system. The
      efficacy of CHOP regimen on Burkitt's lymphoma is poor. The optimal chemotherapy
      regimen needs to be investigated. This study was to evaluate the efficacy of
      modified B-NHL-BFM-90 protocol on Burkitt's lymphoma in children and adolescents,
      and observe the survival status. METHODS: From Oct. 1999 to Nov. 2006, 31
      untreated Burkitt's lymphoma patients aged less than 20 were enrolled. The median
      age of these patients was 5 (range, 1.5-20 years old). Of the 31 patients, 20
      (64.5%) were male, 11 (35.5%) were female. According to St Jude staging system, 1
      (3.2%) was at stage I, 6 (19.4%) at stage II, 8 (25.8%) at stage III, 16 (51.6%)
      at stage IV; 24 (77.4%) were at stage III/IV. According to clinical stage,
      lactate dehydrogenase (LDH) level and treatment response, these patients were
      divided into low, moderate and high risk groups. They received modified B-NHL-BFM
      90 protocol: cytotoxic drugs such as cyclophosphamide, vincristine, ifosfamide,
      etoposide, adriamycin, HD-methotrexate, vindesin, dexamethasone, cytarabinec/HD
      cytarabine and intrathecal injection. RESULTS: One patient died of tumor lysis
      syndrome during prophase. The efficacy was evaluable in 30 patients. Of the 30
      patients, 25 (83.3%) achieved complete remission (CR), 3 (10.0%) achieved partial
      remission (PR), 2 (6.7%) had progressive disease (PD)u 1 had tumor relapse. Grade
      3-4 myelosuppression occurred in most patients and were recovered by active
      support care and did not affect next course of chemotherapy. At a median follow
      up of 33 months (range, 3-98 months), the 3-year event-free survival (EFS) rate
      was 86.0% for all patients, with 100% for stage I/II patients and 82.1% for stage
      III/IV patients, 100% for low risk group, 92.0% for moderate risk group, and
      70.0% for high risk group. CONCLUSIONS: Modified B-NHL-BFM-90 protocol can
      improve the responses and survival of Burkitt's lymphoma in Chinese children and
      adolescents, with tolerable toxicity. It should be used in the experienced cancer
      center and hematological unit.

PMID- 18076799
TI  - [Impact of perioperative chemotherapy on prognosis of colorectal cancer: a report
      of 82 cases].
AB  - BACKGROUND & OBJECTIVE: Recently, some scholars advocate perioperative
      chemotherapy for colorectal cancer. This study aimed to investigate the impact of
      perioperative chemotherapy on the prognosis of colorectal cancer. METHODS: From
      Aug. 2001 to Aug. 2003, 167 patients with Dukes'B or C colorectal cancer were
      randomized into two groups: 82 in trial group received perioperative chemotherapy
      using 5-fluorouracil (5-FU), while 85 in control group received no perioperative
      chemotherapy. All patients received adjuvant chemotherapy of 5-FU/leucovorin
      regimen. The adverse events, recurrence rate and survival rate were compared
      between these two groups. RESULTS: There was no difference in adverse events
      between the two groups. The overall recurrence rate was 42.5%u it was
      significantly lower in trial group than in control group (34.6% vs. 49.4%,
      P=0.038). The overall 1-, 3-, and 4-year survival rates were 97.6%, 74.7% and
      61.8%u they were significantly higher in trial group than in control group (100%
      vs. 95.3%, 82.7% vs. 67.1%, and 69.1% vs. 54.8%, P=0.046). CONCLUSION:
      Perioperative chemotherapy can improve the prognosis of colorectal cancer.

PMID- 18076798
TI  - [Responses of 109 adult soft tissue sarcoma patients to chemotherapy].
AB  - BACKGROUND & OBJECTIVE: The response of adult soft tissue sarcoma (STS) to
      chemotherapy is uncertain. This study was to evaluate the role of chemotherapy in
      treating adult soft tissue sarcoma. METHODS: Clinical data of 109 adult soft
      tissue sarcoma patients, treated with chemotherapy at Cancer Center of Sun Yat
      sen University from Jan. 2000 to Dec. 2005, were analyzed. RESULTS: Of the 109
      patients, 66 received palliative chemotherapy, 40 received adjuvant chemotherapy,
      and 3 received neoadjuvant chemotherapy. The overall response rate for first line
      chemotherapy was 22.7%. The median survival was 16.9 months. The 1-and 2-year
      survival rates were 63.6% and 33.3%. The patients with lung metastasis had a
      significantly longer median survival than those with liver metastasis did (25.1
      months vs. 11.8 months, P<0.05). MAID and CYVADIC were the most commonly used
      first-line chemotherapy regimens; the response rates were 28.0% and 22.2%,
      respectively. When anthracycline and/or standard dose ifosfamide failed, the
      patients could still benefit from high dose ifosfamide (14.0 g/m(2)). The median
      survival was significantly shorter in the patients who got metastasis within 6
      months after diagnosis than in those that got metastasis more than 6 months after
      diagnosis (11.8 months vs. 42.9 months, P=0.04). Of the 40 patients who received
      adjuvant chemotherapy, 16 developed progression during follow-up: 10 had relapse
      and 6 had distant metastasis. CONCLUSIONS: MAID and CYVADIC are two effective
      chemotherapy regimens for adult soft tissue sarcoma. We recommend to take a high
      dose ifosfamide when anthracycline and/or standard dose ifosfamide failed. The
      patients with liver metastasis are more resistant to chemotherapy than those with
      lung metastasis. Developing metastasis within 6 months after diagnosis is a poor
      prognostic factor.

PMID- 18076800
TI  - [Effects of fractionated low dose Cisplatin on renal functions of patients with
      gastric carcinoma].
AB  - BACKGROUND & OBJECTIVE: Cisplatin (DDP) in large dosage impairs renal functions,
      while the impact of fractionated low dose DDP on renal functions is unclear. This
      study was to evaluate the effects of fractionated low dose DDP on renal functions
      of gastric cancer patients. METHODS: From Sep. 1998 to Jun. 2002, 31 gastric
      cancer patients were treated with LFEP regimen at School of Oncology of Peking
      University: intravenous administration of calcium folinate (CF, 150 mg/m(2)) at
      Day 1-3, 5-fluorouracil (5-FU, 500 mg/m(2)) at Day 1-5, epirubicin (EPI, 60
      mg/m(2)) at Day 1, and DDP (20 mg/m(2)) at Day 1-3. Urine N-acetyl-beta-D
      glucosaminidase (NAG), gamma-glutamyl transferase (gamma-GT) and routine urine
      test were assessed before chemotherapy and every other day during the 14-day
      chemotherapy; serum creatinine (sCr) and urea nitrogen (BUN) were assessed at the
      7th day and 14th day during treatment. RESULTS: Of the 31 patients, 13 had normal
      renal functions before chemotherapy, while only 1 had normal renal functions
      after chemotherapy. Urine NAG and gamma-GT were changed significantly after
      chemotherapy: they were increased significantly on the 4th day and maintained
      higher than normal level for another 14 days thereafter. Meanwhile, no
      significant change in sCr and BUN were observed. CONCLUSION: Combined
      chemotherapy with fractionated low dose DDP still adversely affects renal
      functions of gastric cancer patients, however, the long-term effects need to be
      clarified.

PMID- 18076801
TI  - [Efficacy comparison between morphine sulfate controlled-released tablet and
      morphine hydrochloride sustained-released tablet in treating cancer pain].
AB  - BACKGROUND & OBJECTIVE: Morphine sulfate controlled-released tablet and morphine
      hydrochloride sustained-released tablet are preferred medicines for treating
      moderate-severe cancer pain. There are some differences between the two medicines
      in their efficacy, metabolism and adverse events. This study was to compare the
      efficacy and toxicities between morphine sulfate controlled-released tablet and
      morphine hydrochloride sustained-released tablet in treating moderate-severe
      cancer pain. METHODS: A total of 121 patients with moderate-severe cancer pain
      were randomized into two groups: 61 were treated with morphine sulfate controlled
      released tablet and 60 were treated with morphine hydrochloride sustained
      released tablet. Analgesic efficacy and toxicities of the two medicines were
      observed. RESULTS: Of the 61 patients treated with morphine sulfate controlled
      released tablet, 12 had moderate pain, 49 had severe pain; the total response
      rate was 91.80%. Of the 60 patients treated with morphine hydrochloride sustained
      released tablet, 13 had moderate pain, 47 had severe pain; the total response
      rate was 91.67%. There was no significant difference in the efficacy between the
      two medicines. Digestive system adverse events, including nausea, vomiting and
      constipation, were more common in morphine hydrochloride sustained-released
      tablet group than in morphine sulfate controlled-released tablet group (66.66%
      vs. 34.43%, P<0.05). CONCLUSIONS: Both morphine sulfate controlled-released
      tablet and morphine hydrochloride sustained-released tablet are safety in
      treating moderate-severe cancer pain and the toxicities are tolerable. We
      recommend to take morphine sulfate controlled-released tablet for older patients
      and the patients with digestive disorders.

PMID- 18076802
TI  - [Treatment results of stage IA Hodgkin lymphoma: a report of 97 cases].
AB  - BACKGROUND & OBJECTIVE: The treatment strategies of Hodgkin's lymphoma (HL) are
      different according to clinical stage and risk factors, yet the optimal treatment
      strategy remains unclear. This study was to analyze the treatment results and
      prognostic factors of stage IA HL. METHODS: According to prognosis, 97 patients
      with stage IA HL were divided into 3 groups: 7 (7.2%) in very favorable (VF)
      group, 72 (74.2%) in favorable (F) group, and 18 (18.6%) in unfavorable (UF)
      group. Short-term treatment outcome and long-term survival were analyzed. The
      prognosis was analyzed with Cox regression model. RESULTS: Median follow-up time
      was 65 months. After radiotherapy or radiochemotherapy, 90 patients (92.8%)
      achieved complete remission (CR). The 5-and 10-year overall survival (OS) rates
      were 87.7% and 76.3%; the 5-and 10-year disease-free survival (DFS) rates were
      79.4% and 74.5%. The 5-and 10-year OS rates were 100% and 100% in VF group, 88.9%
      and 88.4% in F group, 78.1% and 39.1% in UF group (P=0.292). The 5-and 10-year
      DFS rates were 100% and 87.2% in VF group, 86.3% and 71.8% in F group, 73.6% and
      34.5% in UF group (P=0.032). Cox analysis showed that pathologic type (P=0.056)
      and tumor relapse (P=0.011) influenced OS, and the response to primary treatment
      (P=0.024) influenced DFS. The relapse rate was 18.6%u there was no significant
      difference between the patients received radiotherapy alone and those received
      radiochemotherapy (Chi(2)=0.072, P=0.788). The occurrence rate of secondary
      malignancies was 5.2%, including 2 cases of non-Hodgkin's lymphoma. All the 12
      patients who died had received radiotherapy alone. CONCLUSIONS: More than 90% of
      stage IA HL patients can achieve CR with radiotherapy alone or chemoradiotherapy.
      The long-term OS and DFS of the patients who received radiochemotherapy are
      better than those of the patients who received radiotherapy alone. The pathologic
      type, response to primary treatment and tumor relapse may be independent
      prognostic factors of stage IA HL.

PMID- 18076803
TI  - [Efficacy of adjuvant chemotherapy after left pneumonectomy on non-small cell
      lung cancer].
AB  - BACKGROUND & OBJECTIVE: Presently, whether non-small cell lung cancer (NSCLC)
      patients may benefit from adjuvant chemotherapy after left pneumonectomy is
      controversial. This study was to evaluate the efficacy of adjuvant chemotherapy
      after left pneumonectomy on NSCLC, and explore candidate patient selection for
      adjuvant chemotherapy. METHODS: Clinical data of 51 NSCLC patients received
      radical left pneumonectomy and adjuvant chemotherapy of TP/NP regimen and 102
      patients received left pneumonectomy alone between Jan. 1997 and Jan. 2002 were
      compared. RESULTS: The 1-, 3-, and 5-year survival rates were 88.2%, 54.9%, and
      36.1% in adjuvant chemotherapy group, and 76.5%, 37.3%, and 23.9% in control
      group (P>0.05). For the patients at stage N2 or IIIA, the 1-, 3-, and 5-year
      survival rates were significantly higher in adjuvant chemotherapy group than in
      control group (P<0.05). For the patients with preoperative forced expiratory
      volume at the first second (FEV1) of >2 L, the 1-, 3-, and 5-year survival rates
      were significantly higher in adjuvant chemotherapy group than in control group
      (P<0.05). For the patients aged of >65 or < o r =65, there was no significant
      difference in survival between the two groups (P>0.05). CONCLUSIONS: For the
      NSCLC patients at stage IIIA, N2 or with preoperative FEV1 of >2 L, adjuvant
      chemotherapy after left pneumonectomy may improve survival rate. For the patients
      with good pulmonary function, even aged patients, adjuvant chemotherapy is
      needed.

PMID- 18076804
TI  - [Efficacy of thalidomide combined dexamethasone on newly diagnosed multiple
      myeloma].
AB  - BACKGROUND & OBJECTIVE: Thalidomide is effective in treating refractory and
      relapsed multiple myeloma (MM). However, the efficacy of thalidomide in induction
      therapy for newly diagnosed MM remains unknown. This study was to evaluate the
      efficacy of thalidomide combined dexamethasone (TD induction regimen) on
      previously untreated MM, and observe the adverse events. METHODS: Thirty-nine
      patients with newly diagnosed MM received oral administration of thalidomide at a
      dose of 100-300 mg/day continuously and dexamethasone at a dose of 20-40 mg/day
      on Days 1-4, 9-12, 17-20 in odd months and on Days 1-4 in even months. TD regimen
      was repeated every 28 days. Thirty-six MM patients who received VAD regimen
      (vindesine, adriamycin, and dexamethasone) was regarded as a historical matched
      controls. The efficacy, survival time and adverse events were compared between
      the two groups. RESULTS: The overall response rates were 71.8% in TD group and
      61.1% in VAD group (P>0.05). The median progression-free survival was 14 months
      in TD group and 9 months in VAD group (P>0.05). Within a median follow-up of 13
      months (range, 1-30 months), median overall survival (OS) was not reached in TD
      group, and was 29 months in VAD group. The most common adverse events (always not
      higher than grade 2) were constipation, fatigue, dizziness and somnolence in TD
      group. More grade 3-4 adverse events, included leucopenia and thrombocytopenia,
      and higher infection rate were observed in VAD group as compared with those in TD
      group (P<0.05). CONCLUSIONS: The combination of thalidomide and dexamethasone is
      an effective induction regimen for newly diagnosed MM. It may be considered as a
      replacement of VAD regimen.

PMID- 18076805
TI  - [Efficacy and toxicity of gemcitabine combined vinorelbine on metastatic breast
      cancer: a report of 34 cases].
AB  - BACKGROUND & OBJECTIVE: Chemotherapy is one of major treatments of metastatic
      breast cancer. Anthracyclines and taxanes are usually considered as the most
      active agents in breast cancer and are often used as adjuvant or first-line
      therapy. Gemcitabine and vinorelbine are active agents in breast cancer. This
      study was to evaluate the efficacy of gemcitabine combined vinorelbine on the
      patients with metastatic breast cancer, who had previously received treatment of
      anthracyclines and/or taxanes. METHODS: Thirty-four patients with metastatic
      breast cancer, who had been previously treated with anthracyclines alone or with
      taxanes, were enrolled. The patients received 30-minute intravenous injection of
      gemcitabine (1 000 mg/m(2)) and intravenous bolus injection of vinorelbine(25
      mg/m(2)) on Days 1 and 8; the regimen was repeated every 21 days. RESULTS: A
      total of 109 cycles were given to the 34 patients (median, 3 cycles; range, 1-6
      cycles). The treatment responses were evaluable in all patients. Of the 34
      patients, 9 achieved partial remission (PR), 19 had stable disease (SD), 6 had
      progressive disease (PD)u the response rate was 26.47%. The median time to
      progression was 5.4 months. The median overall survival was 17.8 months. The 1
      year overall survival rate was 68% [95% confidence interval (CI): 50%-86%], the 2
      year overall survival rate was 46% (95% CI: 26%-66%). The major adverse events
      were grade I-II myelosuppression, peripheral neurologic toxicities, nausea and
      vomiting. Some patients had rash and hepatic dysfunction. CONCLUSION: The
      combination of gemcitabine and vinorelbine is an effective and well tolerated
      regimen for the patients with metastatic breast cancer.

PMID- 18076806
TI  - [Efficacy of gemcitabine with concurrent radiotherapy on stage III,inoperable non
      small cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: Radiotherapy is an effective treatment for lung cancer.
      It is still uncertain whether gemcitabine can improve the efficacy of
      radiotherapy on lung cancer. This study was to investigate the efficacy of
      gemcitabine with concurrent radiotherapy on stage III, inoperable non-small cell
      lung cancer (NSCLC), and observe the adverse events and long-term survival of the
      patients. METHODS: Sixty patients were enrolled and divided into trial group (30
      cases) and control group (30 cases). In trial group, the patients received weekly
      administration of gemcitabine (400 mg/m(2)) with concurrent radiotherapy at a
      total dose of 60-66 Gy (2.0 Gy dose fraction per day, 5 days per week). In
      control group, the patients received only radiotherapy at the same dosage. The
      responses were evaluated according to WHO criteria. The efficacy, adverse events
      and long-term survival between the 2 groups were compared with Chi(2) test. The
      long-term survival was also estimated by Kaplan-Meier method. RESULTS: Fifty
      eight patients finished the trial. The follow-up rate was 96.7%. The response
      rate was 70.0% in trial group and 60.0% in control group (P>0.05). There was no
      significant difference in the incidence of hematologic and non-hematologic
      adverse events between the 2 groups (P>0.05). The 1-, 2-, and 3-year survival
      rates were 77.7%, 58.6%, 26.4% in trial group, and 70.3%, 30.1%, 16.1% in control
      group (P>0.05). CONCLUSIONS: In this study, gemcitabine with concurrent
      radiotherapy, as compared with radiotherapy alone, prolonged the survival of
      stage III, inoperable non-small cell lung cancer patients, but the improvement is
      not significant. In both groups, the adverse events are tolerable.

PMID- 18076807
TI  - [Efficacy of gemcitabine combined oxaliplatin on advanced pancreatic cancer].
AB  - BACKGROUND & OBJECTIVE: Gemcitabine (GEM) is efficient in treating advanced
      pancreatic cancer. Preliminary clinical studies showed that the efficacy of
      gemcitabine combined oxaliplatin (GEMOX regimen) is better than that of
      gemcitabine alone. But in China, the use of GEMOX regimen for advance pancreatic
      cancer has seldom been reported. This study was to analyze the efficacy of GEMOX
      regimen on advanced pancreatic cancer, and observe the adverse events. METHODS:
      Clinical data of 32 chemonaive patients with stage III-IV pancreatic cancer,
      treated with GEMOX regimen [intravenous injection of gemcitabine (1 000 mg/m(2))
      at Day 1 and Day 8, and intravenous injection of oxaliplatin (85-130 mg/m(2)) at
      Day 1; repeated every 21 days] at Cancer Center of Sun Yat-sen University from
      Feb. 2001 to Jun. 2006, were reviewed. RESULTS: Of the 32 patients, 8 achieved
      partial remission (PR), 8 had stable disease (SD), and 12 had progressive disease
      (PD)u the objective responses were not assessable (NA) in 4 patients. The
      response rate was 25.0%, and the clinical benefit response (CBR) rate was 46.9%
      (15 patients). The progression-free survival (PFS) was 4.7 months; the median
      overall survival was 8.6 months; the 1-year survival rate was 32.6%. The total
      occurrence rate of myelosuppression was 70.9%u the occurrence rate of grade III
      IV myelosuppression was 32.3%: 12.9% for anemia, 19.4% for neutropenia, and 22.6%
      for thrombocytopenia. The occurrence rate of gastrointestinal adverse events was
      56.2%u only 2 patients had grade III vomiting. Liver function damage (grade I-II)
      occurred in 8 (25.0%) patients; peripheral neurotoxicity (grade I) occurred in 14
      (43.8%) patients. No chemotherapy-related death occurred. CONCLUSIONS: GEMOX is
      an effective regimen for pancreatic carcinoma with good clinical tolerance. The
      main adverse event is myelosuppression.

PMID- 18076808
TI  - [Correlation of peripheral blood micrometastasis to distant metastasis of breast
      cancer].
AB  - BACKGROUND & OBJECTIVE: Breast cancer, a whole body disease, can metastasize at
      early stage. This study was to explore the correlation of peripheral blood cancer
      cell (PBCC) content to distant metastasis of breast cancer. METHODS: The PBCC
      content of 65 breast cancer patients and 8 healthy donors was detected by multi
      parameter flow cytometry (FCM) with CD45 and cytokeratin staining. RESULTS:
      Cancer cells were detected in peripheral blood samples from 57 of the 65
      patients; the positive rate was 87.7%. No cancer cell was found in peripheral
      blood samples from healthy donors. The positive rate of PBCCs was correlated to T
      stage (r=0.271,P=0.017) and N stage (r=0.393, P=0.002). The patients were
      followed for 5 years; 2 were lost. Distant metastasis was found in 25 patients
      with PBCCs. In contrast, no metastasis was found in 8 patients without PBCCs
      (P<0.05). CONCLUSION: Preoperative PBCC content is closely related to distant
      metastasis of breast cancer. The detection of PBCCs might be useful for
      individual treatment decision for breast cancer.

PMID- 18076809
TI  - [Isolation and identification of tumor stem-like cells from human glioma cell
      line U87 after treatment of vincristine].
AB  - BACKGROUND & OBJECTIVE: Tumor stem cells (TSCs) possess the ability of
      chemoresistance. This study was to isolate and identify TSCs from human glioma
      cell line U87. METHODS: After U87 cells were grown as monolayer attached at the
      bottom of flasks in the medium containing serum, neural stem cell culture medium
      containing 5 ng/ml vincristine was added to obtain the first generation of
      tumorosphere. Then, the first generation of tumorosphere was dissociated into
      single cell suspension and seeded in the neural stem cell culture medium to
      obtain the second generation of tumorosphere. The morphology of the first and the
      second generations of tumorosphere was observed by light and scanning electron
      microscopy, respectively. The expression of nestin, glial fibrillary acidic
      protein (GFAP), beta-tubulin III and myelin basic protein (MBP) in the second
      generation of tumorosphere and differentiated cells were determined by
      immunofluorescence assay and confocal laser scanning microscopy. RESULTS: The
      first and second generations of tumorosphere were obtained successfully. Cells
      inside the second generation of tumorosphere with a few protrusions attached with
      each other tightly. The expression of nestin, a stem cell marker, was detected in
      the second generation of tumorosphere. The expression of nestin, GFAP, beta
      tubulin III, MBP was detected in the differentiated cells derived from the second
      generation of tumorosphere. CONCLUSION: Tumor stem cells with the capacity of
      self-renewal and multipotency exist in U87 cells. Selective culture of tumor
      cells with treatment of vincristine might be a simple and practical method for
      isolation of TSCs.

PMID- 18076810
TI  - [A new treatment protocol targeting tumor vasculature--- metronomic chemotherapy
      combined radiotherapy].
AB  - Tumor growth and metastasis depend on its angiogenesis ability. The anti
      angiogenic treatment is considered as a hopeful treatment for tumors. The anti
      angiogenic efficacy of classic cytotoxic agents, such as cyclophosphomide,
      methotraxate, taxol, and so on, could be enhanced by changing the dose delivering
      schedule, naming "metronomic chemotherapy". Additionally, tumor vasculature and
      hypoxic status are important predictive factors for the efficacy of radiotherapy.
      Furthermore, the anti-angiogenic treatment can enhance the irradiation
      sensitivity of tumors. This review have summarized the anti-angiogenic mechanism
      of metronomic chemotherapy combined radiotherapy and the preliminary applications
      in clinic and proposed that the combination of radiotherapy and metronomic
      chemotherapy can overcome the hypoxia-related radioresistance and increase the
      efficacy of radiotherapy.

PMID- 18076811
TI  - [mTOR signal pathway and its inhibitors in antitumor therapy: a review].
AB  - Mammalian target of rapamycin (mTOR) is a key downstream molecule of PI3K/Akt
      pathway. It integrates input signals from growth factors, nutrients and energy to
      regulate cell growth and proliferation via different cellular processes. Gene
      mutations of mTOR pathway-related proteins are very common in many carcinomas.
      Abnormal expression of these related proteins can result in aberrant
      hyperactivity of mTOR pathway. Therefore, mTOR-targeted therapy has shown
      promising role in the management of various cancers. This article reviewed the
      current status of researches on mTOR and its inhibitors in antitumor therapy.

PMID- 18076812
TI  - "My practice is full and I can't take any new patients".

PMID- 18076813
TI  - President's message. Need for a national rural health strategy.

PMID- 18076814
TI  - Nurse-Physician Collaborative Partnership: a rural model for the chronically ill.
AB  - INTRODUCTION: Accessibility and quality of primary health care services in rural
      areas are challenging issues, particularly for the elderly and those with chronic
      or complex medical conditions. The objective of the Nurse-Physician Collaborative
      Partnership was to implement and evaluate a collaborative partnership between
      homecare nurses and family physicians in the rural Trochu-Delburne-Elnora area of
      Alberta. METHODS: Overall, 37 patients were enrolled in a shared care plan, which
      included comprehensive biopsychosocial assessment, early intervention, health
      education and self-management. Patient and provider outcomes were assessed using
      quantitative and qualitative data collected at baseline, 6 months and 12 months.
      RESULTS: Results showed that patients made improvements in activities of daily
      living and robust cognitive status. In interviews, patients reported improvements
      in psychological well-being, knowledge of disease processes and confidence to
      manage health issues. Patients' use of acute health care services decreased,
      showing a 51% reduction in the number of days in hospital, a 32% reduction in
      emergency department visits and a 25% reduction in hospital admissions. Total
      acute service costs, excluding program costs, decreased by 40% from an average of
      $15,485 to $9,313 per person (p < or = 0.05). CONCLUSION: Based on these results,
      policy initiatives that incorporate the shared care model developed in this
      project may be considered. To our knowledge, this type of evaluation has not
      previously been conducted in a rural Canadian setting.

PMID- 18076815
TI  - Factors associated with career satisfaction among general practitioners in
      Canada.
AB  - INTRODUCTION: There are important differences in rural, regional and urban
      general practice environments. The purpose of this study was to articulate models
      that explain career satisfaction among general practitioners (GPs) in these
      practice environments. METHODS: Of 4958 eligible physicians across Canada, 2810
      (56.7%) completed a 12- page survey between January and March 2004, from whom a
      total of 256 GPs in rural, regional and urban communities were selected. Response
      bias was checked and found to be negligible. We used hierarchical regression
      analysis to record cumulative R2, standardized beta and significance levels as
      each predictor was entered. We applied weighting factors to reflect the actual
      physician population in Canada. RESULTS: The models explained 88.5% of the
      variance in career satisfaction for GPs in small towns, 88.9% for GPs in regional
      communities and 86.3% for GPs in urban cities. The explanatory variables
      consisted of distress and coping, role in community activities, the quality of
      health care services and access to them, intrinsic and extrinsic rewards,
      workload and organizational structure. CONCLUSION: Career satisfaction for small
      town doctors is associated with being able to cope with stress in handling a wide
      variety of clinical conditions, largely on their own, but with effective
      collaboration from physicians in larger centres. Rural GPs also enjoy academic
      responsibilities. Satisfaction for GPs in regional communities also depends on
      coping with stress and the ability to maintain an efficiently operating set of
      secondary- level health services in their community. Satisfaction for urban GPs
      is associated with collegiality, which dampens stress, and access to a full range
      of health services, including community, hospital, mental health and
      rehabilitation services. Career satisfaction for all GPs is associated with
      equity, manageable workloads and effective practice management; however, all of
      these professional issues contribute, in small increments, to satisfaction.

PMID- 18076816
TI  - The ARTS of risk management in rural and remote medicine.
AB  - INTRODUCTION: This paper describes an action research process (in which the
      researchers are active participants throughout the process of development,
      testing and refinement) to develop a framework for clinical risk assessment and
      management in the context of rural and remote medicine. The framework is needed
      to support educational, medicolegal and quality improvement processes in rural
      and remote medical practice. METHODS: The research process included identifying a
      problem and gradually developing a research question, developing a potential
      model for application in a specific context, refining the tool and piloting the
      tool in a limited context. The research question and framework were developed
      during a series of teleconferences under the aegis of the Censorial Panel of the
      Australian College of Rural and Remote Medicine (ACRRM). After the framework was
      developed and refined, it was tested at a workshop in conjunction with the ACRRM
      Scientific Forum in Alice Springs, Australia, in July 2004. Workshop participants
      were principally but not exclusively rural medical practitioners from across
      Australia. The main outcome measure was a working framework for risk management
      broadly applicable in rural and remote medicine. RESULTS: The process clarified
      differences between safety and quality approaches in metropolitan and rural and
      remote medical practice, culminating in an appropriate clinical risk management
      framework. CONCLUSION: The action research as undertaken resulted in a workable
      risk management framework that is worthy of further development and that may be a
      valuable educational tool, both for existing practitioners and for future rural
      doctors. Further, it has potential as a means of providing legal protection to
      rural practitioners when actual rural practice is at odds with "best practice" as
      defined by a metropolitan group of experts.

PMID- 18076817
TI  - A large splenic epidermoid cyst in rural Labrador.

PMID- 18076818
TI  - The occasional trigger point injection.

PMID- 18076819
TI  - Factors affecting rural medicine: an improvement on the Rurality Index of
      Ontario.

PMID- 18076820
TI  - Altering systemic acid-base balance through nutrition failed to change secondary
      sex ratio.
AB  - There is evidence that differences in either maternal blood pH or dietary mineral
      content can result in alterations in secondary sex ratio in mammals. Altering the
      proportions of certain dietary minerals is known to influence blood pH, offering
      a possible explanation for this effect of diet on secondary sex ratio. The
      present study was performed to investigate whether altering blood pH by
      manipulating the dietary cation-anion difference (DCAD) would alter secondary sex
      ratio. The DCAD is calculated (in mEq per 100 g dry matter) as the difference
      between metabolically strong cations (Na + K) and metabolically strong anions (Cl
      + S) in the diet. Three hundred female mice were randomly allocated to either a
      low or high DCAD ration for 3 weeks before coitus. Urine pH was monitored before
      beginning the experiment, as well as before and after the breeding period, as a
      proxy for blood pH. Mice on the low DCAD diet had a lower urine pH (mean (+/-
      s.d.) 6.0 +/- 0.1) than mice on the high DCAD diet (8.2 +/- 0.6), but DCAD did
      not affect the percentage of mice that became pregnant, the number of offspring
      per pregnant mouse or the sex ratio of the neonate group. These results suggest
      that blood pH alone does not alter sex ratio and that an altered systemic pH is
      not the reason for reported mineral-related variations in sex ratio.

PMID- 18076821
TI  - Pituitary and testicular endocrine responses to exogenous gonadotrophin-releasing
      hormone (GnRH) and luteinising hormone in male dogs treated with GnRH agonist
      implants.
AB  - The present study tested whether exogenous gonadotrophin-releasing hormone (GnRH)
      and luteinising hormone (LH) can stimulate LH and testosterone secretion in dogs
      chronically treated with a GnRH superagonist. Twenty male adult dogs were
      assigned to a completely randomised design comprising five groups of four
      animals. Each dog in the control group received a blank implant (placebo) and
      each dog in the other four groups received a 6-mg implant containing a slow
      release formulation of deslorelin (d-Trp6-Pro9-des-Gly10-LH-releasing hormone
      ethylamide). The same four control dogs were used for all hormonal challenges,
      whereas a different deslorelin-implanted group was used for each challenge.
      Native GnRH (5 microg kg(-1) bodyweight, i.v.) was injected on Days 15, 25, 40
      and 100 after implantation, whereas bovine LH (0.5 microg kg(-1) bodyweight,
      i.v.) was injected on Days 16, 26, 41 and 101. On all occasions after Day 25-26
      postimplantation, exogenous GnRH and LH elicited higher plasma concentrations of
      LH and testosterone in control than deslorelin-treated animals (P < 0.05). It was
      concluded that, in male dogs, implantation of a GnRH superagonist desensitised
      the pituitary gonadotrophs to GnRH and also led to a desensitisation of the
      Leydig cells to LH. This explains, at least in part, the profound reduction in
      the production of androgen and spermatozoa in deslorelin-treated male dogs.

PMID- 18076822
TI  - Effects of deslorelin implants on reproduction in the common brushtail possum
      (Trichosurus vulpecula).
AB  - The present study investigated the effects of slow-release implants containing
      the gonadotrophin-releasing hormone (GnRH) agonist deslorelin on reproduction in
      the common brushtail possum (Trichosurus vulpecula). Captive female brushtail
      possums were assigned to control (placebo implant), low dose (4.7 mg deslorelin)
      or high dose (9.4 mg deslorelin) groups; males were assigned to control or high
      dose (9.4 mg deslorelin) groups. The acute effects of deslorelin treatment at the
      level of the pituitary gland were similar between the two sexes, where a
      transient rise in luteinising hormone concentration was induced over the first 24
      h. In females, this was associated with the disruption of the normal oestrous
      cycle and mating within 2-10 days in some treated individuals, but no young were
      subsequently detected. By 3 weeks after treatment, treated females became
      anoestrus and remained infertile for at least one breeding season. The effects of
      treatment were reversible in a subset of females that had their implants removed,
      although the time taken to produce offspring was variable. Paradoxically, male
      brushtail possums remained fertile during chronic deslorelin exposure. Despite
      significant declines in basal follicle-stimulating hormone and testosterone
      concentrations, as well as an inability to respond to a GnRH challenge, treated
      males sired as many offspring as control males and there was no evidence of
      testicular regression. In conclusion, there is potential to control reproduction
      in female brushtail possums by using chronic GnRH agonist treatment.

PMID- 18076823
TI  - Enhancing ultrasound texture differences for developing an in vivo 'virtual
      histology' approach to bovine ovarian imaging.
AB  - A 'virtual histology' can be thought of as the 'staining' of a digital ultrasound
      image via image processing techniques in order to enhance the visualisation of
      differences in the echotexture of different types of tissues. Several candidate
      image-processing algorithms for virtual histology using ultrasound images of the
      bovine ovary were studied. The candidate algorithms were evaluated qualitatively
      for the ability to enhance the visual differences in intra-ovarian structures and
      quantitatively, using standard texture description features, for the ability to
      increase statistical differences in the echotexture of different ovarian tissues.
      Certain algorithms were found to create textures that were representative of
      ovarian micro-anatomical structures that one would observe in actual histology.
      Quantitative analysis using standard texture description features showed that our
      algorithms increased the statistical differences in the echotexture of stroma
      regions and corpus luteum regions. This work represents a first step toward both
      a general algorithm for the virtual histology of ultrasound images and
      understanding dynamic changes in form and function of the ovary at the
      microscopic level in a safe, repeatable and non-invasive way.

PMID- 18076824
TI  - Caspase-3-mediated apoptosis and cell proliferation in the equine endometrium
      during the oestrous cycle.
AB  - Cell proliferation and apoptosis are hormone-dependent physiological processes
      involved in endometrial growth and regression. The aims of the present study
      were: (1) to evaluate endometrial cell proliferation using proliferating cell
      nuclear antigen (PCNA) expression; (2) to evaluate the induction of endometrial
      cell death by the expression of active caspase-3 and the apoptotic phenotype
      visualised by DNA fragmentation; and (3) to relate these observations to
      endometrial tissue dynamics in the equine endometrium throughout the oestrous
      cycle. Endometria were assigned to follicular and luteal phases based on ovarian
      structures and plasma progesterone. Cell proliferation and active caspase-3
      mediated apoptosis were expressed in both phases of the oestrous cycle. In the
      luteal phase, PCNA expression was higher than in the follicular phase. Highest
      PCNA activity was noted in the luminal and glandular structures. Active caspase-3
      staining was increased in luminal epithelium and deep glandular cells during the
      luteal phase. However, in the follicular phase, stromal cells showed greater
      active caspase-3 expression. Only a few apoptotic endometrial cells were detected
      by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end
      labelling (TUNEL) and these cells were mostly present in luminal and glandular
      structures. A simultaneous increase in DNA, cell proliferation and protein
      synthesis was observed in the endometrium during the mid-luteal phase. This
      suggests that cell hyperplasia occurs at the time the histotroph is needed for
      eventual embryo nourishment.

PMID- 18076825
TI  - Enzymatic removal of asparagine-linked carbohydrate chains from heterodimer human
      chorionic gonadotrophin and effect on bioactivity.
AB  - The native form of human chorionic gonadotropin (hCG) is a heterodimer protein
      with two asparagine (Asn)-linked carbohydrate chains on each subunit. Removal of
      the Asn-linked carbohydrate chains from hCG has resulted in hCG variants with
      consistent antagonistic properties on isolated murine cells. Specific and direct
      enzymatic removal of these carbohydrate chains from native hCG with resultant
      antagonistic properties has not been reported. An antagonist to the
      hCG/luteinising hormone (LH) receptor could be used as an anticancer therapy,
      emergency contraceptive or for therapeutic resolution of ectopic pregnancies.
      Therefore, our aim was to use enzymes to specifically remove Asn-linked
      carbohydrate chains from hCG in the heterodimer form and analyse the resultant
      bioactivity. Native hCG was treated with endoglycosidases, carbohydrate removal
      was analysed with electrophoresis and the hCG variants were tested for altered
      bioactivity with human and murine cells. Endoglycosidases were able to cleave
      most of the Asn-linked carbohydrate chains from the native hCG. The
      deglycosylated hCG demonstrated a 75% reduction in bioactivity on a murine Leydig
      cell line and a 65% reduction in bioactivity on human granulosa cells. These
      results exemplify a simple and efficient method for creating deglycosylated hCG
      and provide the most direct evidence for the importance of Asn-linked
      carbohydrate chains in maintaining hCG bioactivity.

PMID- 18076826
TI  - Effect of GnRH treatment on the maturation and in vitro development of oocytes
      collected from 4- to 6-week-old Merino lambs.
AB  - Two experiments were conducted in Merino lambs to examine the effects of
      gonadotrophin-releasing hormone (GnRH) treatment on the developmental competence
      of oocytes collected after pretreatment with follicle stimulating hormone (FSH).
      The first experiment examined the effects of six GnRH treatment times (control
      and GnRH administered 2, 4, 6, 8 and 10 h before oocyte collection) and four in
      vitro maturation (IVM) periods (18, 20, 22, 24 h) on the rate of oocyte nuclear
      maturation. The second experiment examined the effect of five GnRH treatment
      times (control and GnRH administered 2, 4, 6 and 8 h before oocyte collection)
      and three IVM periods (20, 22, 24 h) on the development of oocytes and embryos
      after in vitro maturation, fertilisation and culture. In Experiment 1, GnRH
      treatment did not influence the mean number of cumulus-oocyte-complexes (COCs)
      collected or COC morphology at the time of collection. However, treatment changed
      (P < 0.01) the distribution of follicle size and this was primarily due to a
      marked reduction in the number of follicles with diameters <2 mm. In addition,
      GnRH treatment at 6 and 8 h increased (P < 0.01) the proportion of oocytes that
      developed to Metaphase II (MII) (63.2 and 72.6%, respectively) compared with
      other treatment times (range 52.9-59.9%). Nuclear maturation was influenced by a
      significant (P < 0.05) interaction between GnRH treatment and IVM period due to a
      disproportionately greater number of oocytes at the germinal vesicle breakdown
      (GVBD) stage for the 2 and 4 h GnRH treatments compared with other treatments. In
      Experiment 2, cleavage rate (range 63.5-85.9%) was highest when GnRH was
      administered 8 h before collection but the percentage of cleaved oocytes that
      developed into blastocysts (range 10.0-35.0%) was significantly (P < 0.05) lower
      for the 6 and 8 h GnRH treatments compared with the control and the 2 h GnRH
      treatment. These results demonstrate that GnRH treatment before oocyte collection
      can improve nuclear maturation and cleavage rates in lamb oocytes but that these
      improvements are not reflected in improved rates of blastocyst development. It is
      speculated that this discrepancy may result from GnRH treatment either adversely
      affecting cytoplasmic maturation or inducing asynchrony between the maturation of
      the nuclear and cytoplasmic components of the oocyte.

PMID- 18076827
TI  - Sympathetic pharmacological denervation in ageing rats: effects on ovulatory
      response and follicular population.
AB  - The present study analyses the participation of ovarian innervation during
      reproductive senescence. We use the model of acute peripheral pharmacological
      sympathetic denervation with guanethidine in young (3 months old), middle-aged
      (12 months old) or old (18 months old) rats with spontaneous or induced
      ovulation. Ovarian levels of norepinephrine (NE) were measured by HPLC and the
      oestrous cycle, the number of ovulating animals and the percentage of atretic
      follicles were also assessed. Aged animals showed a progressive reduction in
      ovulatory capacity and an increase in ovarian NE content. Acute denervation
      increased the percentage of healthy follicles in 12- and 18-month-old rats
      compared with control adult animals. Combined treatment of denervation plus
      stimulation with gonadotrophins doubled the number of ova shed in young adult
      rats and restablished a partial ovulation in 12-month-old rats. The results
      suggest that ovarian noradrenergic innervation plays a modulator role in ovarian
      physiology during the ageing ovary process. The action of ovarian noradrenergic
      innervation seems to be associated with folliculogenesis and the ovarian response
      to gonadotrophins.

PMID- 18076828
TI  - Pulsatile release of luteinising hormone during the luteal phase in lactating and
      weaned sows.
AB  - The present paper describes luteal phase luteinising hormone (LH) in sows that
      ovulated due to a limited nursing regimen (LN). The LN regimen was imposed either
      at Day 14 or at Day 21 of lactation. At ovulation, lactation was terminated (n =
      8) or sows remained lactating throughout early pregnancy (n = 8). Blood samples
      were collected every 15 min for 8 h during the day, around Day 11 after
      ovulation. In addition, lactating sows were bled during the night, when piglets
      were allowed to suckle. The LH pattern was typical for the luteal phase, with one
      to five pulses per 8 h. The LH characteristics (frequency, base, average, pulse
      area) did not differ between lactating and weaned sows, except for the amplitude
      of LH pulses, which was higher in weaned sows compared with lactating sows (1.22
      +/- 0.15 v. 0.76 +/- 0.11 ng mL(-1), respectively; P < 0.05). In lactating sows,
      average LH, basal LH and the frequency of LH pulses were significantly lower
      during the night, when piglets were allowed to suckle. The sage of lactation at
      which LN was imposed did not influence LH. In conclusion, it is unlikely that the
      small difference in LH explains the considerable difference between lactating and
      weaned sows in progesterone at Day 12 of pregnancy (24.1 +/- 1.3 v. 43.3 +/- 4.0
      ng mL(-1), respectively; P < 0.01). Moreover, the difference in progesterone
      already exists during the early luteal phase (Day 0-10), when secretion of the
      corpora lutea is still independent of LH.

PMID- 18076829
TI  - Identification of novel genes associated with dominant follicle development in
      cattle.
AB  - Follicle development is regulated by the interaction of endocrine and
      intrafollicular factors, as well as by numerous intracellular pathways, which
      involves the transcription of new genes, although not all are known. The aim of
      the present study was to determine the expression of a set of unknown genes
      identified by bovine cDNA microarray analysis in theca and granulosa cells of
      dominant and subordinate follicles, collected at a single stage of the first
      follicular wave using quantitative real-time polymerase chain reaction.
      Differences were further examined at three stages of the follicular wave
      (emergence, selection and dominance) and bioinformatics tools were used to
      identify these originally unknown sequences. The suggested name function and
      proposed role for the novel genes identified are as follows: MRPL41 and VDAC2,
      involved in apoptosis (dominant follicle development); TBC1D1 stimulates cell
      differentiation (growth associated with dominant follicle selection and
      development); STX7, promotes phagocytosis of cells (subordinate follicle
      regression); and SPC22 and EHD3, intracellular signalling (subordinate follicle
      regression). In conclusion, we have identified six novel genes that have not been
      described previously in ovarian follicles that are dynamically regulated during
      dominant follicle development and presumably help mediate intracellular
      signalling, cell differentiation, apoptosis and phagocytosis, events critical to
      follicular development.

PMID- 18076830
TI  - Perturbed growth and development in marsupial young after reciprocal cross
      fostering between species.
AB  - Cross-fostering of marsupial young between species can potentially facilitate
      propagation of endangered or rare marsupial species by artificially increasing
      the number of progeny produced. The present study compares the growth and
      development of normal and cross-fostered tammar and parma wallabies. Tammars
      cross-fostered into the pouches of parmas grew at a similar rate to naturally
      reared tammar young and had developmental milestones at a similar age. However,
      parma young cross-fostered between the day of birth and 15 days post-partum into
      tammars that were carrying young of equivalent developmental stages did not grow
      normally and were lost from the pouch. Parma young cross-fostered at 30 days
      survived, but had significantly reduced growth rates and their developmental
      milestones were delayed compared with normally reared parma young. Thus, growth
      can be affected by cross-fostering, even between species like tammars and parmas
      that are of similar size and have similar lactation lengths. The results of the
      present study suggest that maternal milk regulates the timing of development of
      each species and a mis-match in the time that each young receives critical milk
      components can have a marked effect on their growth and development.

PMID- 18076831
TI  - Emergency prevention of extinction of a transgenic allele in a less-fertile
      transgenic mouse line by crossing with an inbred or outbred mouse strain coupled
      with assisted reproductive technologies.
AB  - Certain transgenic mouse lines are difficult to breed or archive and,
      consequently, their transgenes become lost. We examined a C57BL/6 mouse line (B6
      tg), transgenic for green fluorescent protein (GFP) with low fertility, and its
      crosses with the more prolific inbred C3HeB/FeJ (C3) and outbred Swiss (SW)
      strains in order to assess the possibility of emergency prevention of extinction
      of a transgenic allele by using assisted reproductive technologies (ART). Out
      crossing was performed by natural mating or in vitro fertilisation (IVF) with
      heterozygous mice. Most of the crossing combinations resulted in improved
      archiving and rederivation efficiencies of the transgenic allele. Natural
      crossing increased both mean litter size by two to three pups and the
      superovulatory rate from 69% for B6-tg to 70-90% for females from the out
      crosses. Each plug-positive B6-tg female yielded an average of 4.6 two-cell
      embryos, whereas females from the out-crosses produced three- to fivefold that
      amount. After thawing, 13% of B6-tg embryos and 6-12% of out-crossed embryos
      developed into transgenic pups after transfer into recipients. After IVF with
      cryopreserved spermatozoa, cleavage rates were 4% for B6-tg, 22-37% for B6-tg
      oocytes out-crossed with C3 and SW spermatozoa, 9-49% for gametes from out
      crossed mice and 28-44% for back-crosses with B6 oocytes. Transgenic pups were
      not derived from IVF with B6-tg gametes when either fresh or cryopreserved
      spermatozoa were used. Rederivation efficiencies were 7% and 4% from out-crosses
      of B6-tg oocytes with C3 and SW spermatozoa, respectively, 6-22% for gametes from
      out-crossed mice and 4-10% for the back-crosses. Although out-crossing changes
      the original genetic background, the strategy of crossing coupled with ART
      prevents the extinction of an allele of interest, especially where archiving and
      rederivation of the transgenic line fail.

PMID- 18076832
TI  - Kimura disease: an unusual cause of cervical lymphadenopathy with salivary gland
      involvement.

PMID- 18076833
TI  - Relapsing polychondritis: a case with subglottic stenosis and laryngotracheal
      reconstruction.

PMID- 18076834
TI  - Secondary renal cell carcinoma of the head and neck.

PMID- 18076835
TI  - Aggressive cemento-ossifying fibroma.

PMID- 18076836
TI  - Metastatic acinic cell carcinoma presenting as a recurrent pituitary adenoma.

PMID- 18076837
TI  - Intravagal ectopic parathyroid presenting as vocal cord paralysis: case report
      and review of the literature.

PMID- 18076838
TI  - Nasogastric tube syndrome.

PMID- 18076839
TI  - Sialolithiasis with concurrent sialadenitis in an 18-year-old boy with triple A
      syndrome.

PMID- 18076840
TI  - Vestibular compensation after unilateral labyrinthectomy: normal versus
      cerebellar dysfunctional mice.
AB  - INTRODUCTION: Loss of vestibular information from one labyrinth produces marked
      asymmetries of postural and ocular motor control, which resolve over time. Recent
      developments in mouse genetic engineering, which allow the generation of
      transgenic and knockout mutant mice, provide a unique opportunity to bridge the
      gap between the molecular mechanisms that underlie compensation and behaviour.
      METHOD: We compared compensation following unilateral labyrinthectomy in wild
      type mice and a cerebellar-dysfunctional mouse (the Lurcher mutant). The Lurcher
      mutant is characterized by a point mutation in the ionotropic glutamate receptor
      delta 2 subunit gene that results in loss of all Purkinje cells. To further
      investigate this question, we characterized vestibular compensation in a strain
      of mutant mice that completely lack cerebellar Purkinje cells. RESULTS: Static
      signs resolved within 24 hours in wild-type mice but did not fully resolve in
      Lurcher mice. Dynamic signs were evaluated by the quantitative analysis of
      vestibulo-ocular (VOR) and vestibulocollic (VCR) reflexes. The VOR assessed at
      0.5 Hz exhibited increasing gain from day 1 to day 5, reaching control levels by
      day 20 for the wild-type mice. In contrast, Lurcher mutant mice showed
      significantly less compensation over this same period. VOR compensation in the
      mutant mice was slightly more robust in response to high acceleration thrusts but
      again never reached control levels. Similarly, VCR gains showed limited
      compensation and remained subnormal in mutant mice. CONCLUSION: Compensation for
      dynamic signs starts at day 5 after unilateral labyrinthectomy in normal mice.
      Cerebellar dysfunctional mutant mice do not compensate for static signs and show
      limited vestibular compensation for dynamic signs only. We conclude that other
      noncerebellar pathways for vestibular compensation exist, and our findings
      emphasize the need for these to be further explored.

PMID- 18076841
TI  - Multimodal multidisciplinary surgical approach for the treatment of pituitary
      tumours.
AB  - OBJECTIVES: The surgical management of pituitary tumours is being impacted by the
      development of two key technologies: image guidance and endoscopy. This study
      sought to assess their impact. METHODS: Retrospective review of all patients
      referred to the Skull Base Clinic of the McGill University Health Centre since
      2000. Patients were operated on in a multidisciplinary context using a multimodal
      approach combining endoscopy and microscopy. Imaging during the surgery was
      initially supported by both three-dimensional neuronavigation and traditional C
      arm fluoroscopy. RESULTS: Seventy-five patients were referred to the
      multidisciplinary clinic, for a total of 41 surgeries. Neuronavigation was used
      in all cases. C-arm fluoroscopy was not found to improve our surgeries and was
      removed from our protocol. Endoscopy was found to be advantageous as it allowed
      improved visualization. It also permitted identifying surrounding structures in
      the lateral wall of the sphenoid sinus, next to the tumour, and "around corners."
      Moreover, it encouraged multidisciplinary co-operation as it allowed
      neurosurgeons and otolaryngologists to follow progress during the case.
      Nevertheless, the microscope continued to play a role as it facilitated a
      bimanual technique, stable magnification, and a three-dimensional view.
      Morbidities in our case series appeared to be minimal. CONCLUSION: Both endoscopy
      and the microscope were found to have a role in our surgeries. We consider these
      technologies to be complementary. C-arm fluoroscopy was rendered obsolete by the
      neuronavigation unit. A multidisciplinary, multimodal approach maximizes the
      benefits of these new technologies and permits the best surgical result.

PMID- 18076842
TI  - Brachytherapy in the retreatment of patients with new primary head and neck
      cancer.
AB  - OBJECTIVE: Re-treatment for cure of the Head and Neck (H&N) region is
      therapeutically challenging. In this review we explore the long-term results of
      Ir(192) low-dose-rate (LDR) brachytherapy in the select subgroup of patients
      treated for a new H&N malignancy. METHODS & MATERIAL: Thirteen patients received
      brachytherapy between 1987-2004 for a new primary H&N cancer, six of whom had
      been retreated previously. Brachytherapy was given as a monotherapy in eight
      patients and delivered adjuvantly in five patients. Three of the thirteen
      patients had advanced disease at the time of diagnosis. MAIN OUTCOME MEASURES: In
      addition to the known prognostic factors of stage and site, intent of
      brachytherapy and prior re-treatment status were assessed for their influence on
      local control (LC) and overall survival (OS). RESULTS: Local control differed by
      disease stage of the new primary tumor. With a median follow-up of 50 months,
      mean progression-free survival was 50.2 months [95%CI = 30.1-70.4] and the 2-year
      rate of LC was 58%. Adjuvant brachytherapy following surgery resulted in poor LC
      and OS due to advanced disease at diagnosis. Prior retreatment did not appear to
      affect LC or OS. OS at 2 and 5 years was 69% and 38%, respectively. There were no
      cases of grade III toxicity. CONCLUSIONS: LDR Brachytherapy for a new primary H&N
      cancer is a well-tolerated retreatment alternative that results in good local
      control. Our results suggest that the best chance for long-term survival remains
      in the routine follow-up and early diagnosis of the new H&N malignancy.

PMID- 18076843
TI  - Wait times in the diagnosis and treatment of head and neck cancer: comparison
      between wait times in 1995 and 2005--a prospective study.
AB  - INTRODUCTION: There are limited studies documenting current wait times in the
      diagnosis and treatment of head and neck cancer. The objective of this study was
      to describe wait times along the health care pathway of head and neck cancer
      patients referred to an oncology centre in Ontario in 2005 and compare these
      times with those in a similar cohort of patients enrolled in 1995. METHODS: A
      cross-sectional study investigating wait times in newly diagnosed patients with
      squamous cell carcinoma of the head and neck was undertaken at the Princess
      Margaret Hospital, Toronto, Ontario. Data were collected prospectively in 2005
      and 1995. Patient interviewing and health care provider corroboration were
      employed for a sample size of 45 patients in 2005 and 40 patients in 1995.
      RESULTS: Median wait times in 2005 were similar to those in 1995 for each time
      period, except for the time from consultation with the first tertiary specialist
      to treatment, which was statistically significantly shorter in 1995 (25 days)
      than in 2005 (37 days), p = .002. The median time from initial primary care
      practitioner seen to treatment (total professional delay) was not different from
      1995 (126 days) to 2005 (115 days), p = .47. On univariate analysis, there were
      no statistically significant differences in wait times in each time period based
      on site (p = .226 and .321, respectively) and overall stage (p = .655 and .538,
      respectively). CONCLUSIONS: Wait times for head and neck cancer treatment from
      the time of initial consultation with an oncologist have increased from 1995 to
      2005.

PMID- 18076844
TI  - Sentinel lymph node biopsy in squamous cell carcinoma of the head and neck: where
      we stand now, and where we are going.
AB  - BACKGROUND AND OBJECTIVES: This review was performed to evaluate the existing
      literature on sentinel lymph node biopsy (SLNB) for early-stage oral and
      oropharyngeal head and neck squamous cell carcinoma (HNSCC) in clinically
      negative (N0) necks. METHODS: A Medline search identified 43 pertinent published
      trials and reviews in the English-language literature from 1990 to 2005. RESULTS:
      Recent studies consistently show high sensitivities > 93% for T1 and T2 HNSCC.
      SLNB has the potential to replace neck dissection in those patients. Data on T3
      and T4 tumours are not as promising, although research is currently under way to
      determine the true metastasis detection rate. Appropriate technique is crucial
      for the complete detection of the sentinel nodes. For HNSCC sentinel
      lymphadenectomy, many studies have advocated the use of a colloid tracer and
      gamma probe detector, as well as the harvesting of a total of three nodes as a
      good standard technique. CONCLUSIONS: American multicentre trials are currently
      under way gathering crucial data on this technique. It is very likely that SLNB
      will become indicated for T1 and T2 oral cavity squamous cell carcinoma with N0
      necks, and it is possible that the indication will extend to all early-stage
      HNSCCs. However, more research will be necessary for advanced head and neck
      cancers.

PMID- 18076845
TI  - Management of advanced nodal disease following chemoradiation for head and neck
      squamous cell carcinoma: role of magnetic resonance imaging.
AB  - BACKGROUND: The purpose of this study was to determine the role of magnetic
      resonance imaging (MRI) to predict persistent nodal disease in head and neck
      cancer treated with chemoradiation. METHODS: Retrospective chart review of 38
      patients with head and neck cancer and N2/N3 neck disease who were treated with
      chemoradiation and who had an MRI 6 to 8 weeks following treatment. RESULTS:
      Sixteen patients had MRI findings suggestive of persistent nodal disease and were
      managed with neck dissections, three of whom had a persistent tumour. All of
      these patients have remained disease free in the neck (average follow-up 15
      months). Among 22 patients without evidence of nodal disease on post-treatment
      MRI, 2 patients have had recurrence in the neck (average follow-up 26 months).
      CONCLUSIONS: Concomitant chemoradiation is effective for the treatment of
      advanced nodal disease in selected patients. Patients without MRI evidence of
      persistent nodal disease following chemoradiation who were observed had a low
      incidence (9%) of eventual neck recurrence, whereas those with evidence of
      persistent nodes on MRI had a 19% likelihood of residual pathologic neck disease.
      The optimal strategy for the evaluation of the neck following chemoradiation
      requires further investigation.

PMID- 18076846
TI  - Role of vascular endothelial growth factor in the pathogenesis of nasal polyps.
AB  - OBJECTIVE: This study was aimed at determining the expression of vascular
      endothelial growth factor (VEGF) in nasal polyps by immunohistochemical
      technique. METHODS: The study group consisted of 25 adult patients with nasal
      polyps who underwent functional endoscopic sinus surgery. Polyp tissues were
      taken from the maxillary and ethmoid sinuseses and the nasal cavity. The control
      group consisted of three adult patients without nasal polyps who underwent
      septoplasty operation. Their inferior turbinate biopsies were taken with written
      approval. VEGF positivity was scored by the Vascular Endothelial Growth Factor
      Positivity Index (VEGF-PI) in the subepithelial (VEGF-PI-SE) and deep (VEGF-PI
      Deep) layers of the mucosa on a 0 to 3 scale, and the percentage of inflammatory
      cells per 100 cells was found. RESULTS: VEGF expression was identified as
      cytoplasmic staining in the vascular endothelium and inflammatory cells. In each
      of four groups (maxillary and ethmoid sinuses, nasal cavity, and control), no
      significant difference was present between VEGF-PI-SE and VEGF-PI-Deep scores.
      For the VEGF-PI-SE and VEGF-PI-Deep groups, nasal cavity scores were
      significantly higher. For plasma cell count, the nasal cavity value was
      significantly higher. As the plasma cell count increased, VEGF-PI-SE and VEGF-PI
      Deep scores were also increased in all four groups. CONCLUSION: In the nasal
      cavity, VEGF expression is observed more, causing angiogenesis and an increase in
      the vascular permeability. In the paranasal sinuses, lower VEGF-PI results may
      show that contact inhibition reduces VEGF expression and thus the polyp growth
      rate.

PMID- 18076848
TI  - Pulpal expression of TRPV1 in molar incisor hypomineralisation.
AB  - AIM: This was to compare the pulpal expression of the transient receptor
      potential ion channel (TRPV1), a noxious heat receptor, in sound and
      hypomineralised human first permanent molars. The rationale for the investigation
      was to gain further insight into pulpal changes in hypomineralised teeth and the
      possible biological mechanisms underlying thermal hypersensitivity. STUDY DESIGN:
      This was a laboratory study using a quantitative immuncocytochemical approach.
      METHODS: The experimental material comprised 17 sound and 18 hypomineralised
      molars (10 with intact enamel and 8 with enamel loss), obtained from children
      requiring dental extractions under general anaesthesia. Coronal pulps were
      removed and processed for indirect immunofluorescence using antibodies raised
      against TRPV1 and either the general neuronal marker, protein gene-product 9.5 or
      alpha smooth muscle actin in conjunction with Ulex europaeus agglutinin 1 lectin
      to fully label the pulp vasculature. Computerised image analysis was used to
      quantify the expression of TRPV1 in both pulpal nerves and blood vessels within
      different regions of the pulp including the pulp horn, subodontoblastic plexus
      and mid-coronal region. RESULTS: Mean neuronal and vascular TRPV1 expression was
      significantly greater in some pulpal regions of hypomineralised teeth (both with
      and without enamel loss) than for sound samples (p<0.05, ANOVA). CONCLUSIONS:
      Increased TRPV1 expression within the pulps of hypomineralised teeth may be
      indicative of an underlying pulpal inflammation and may help to explain the heat
      sensitivity experienced by some patients with this condition. However, future
      lines of enquiry should seek to correlate patient symptoms and responses to
      controlled hot and cold stimuli with pulpal expression of a variety of thermal
      receptors to gain further insight into dental pain mechanisms.

PMID- 18076849
TI  - Molar incisor hypomineralisation in Bosnia and Herzegovina: aetiology and
      clinical consequences in medium caries activity population.
AB  - AIM: This was to establish the prevalence of MIH among 12-year-old children in
      Bosnia and Herzegovina, and to investigate its aetiological background and
      clinical consequences of MIH in a population with medium caries activity.
      METHODS: MIH prevalence was determined as a part of the first national oral
      health survey in Bosnia and Herzegovina in 2004, conducted on a gender balanced
      sample of 560 12-year-old children, in line with recommended criteria for MIH
      diagnosis and registration. The MIH sub-sample had been selected from the main
      sample and it included children with MIH and their control pairs. The two groups
      were matched in terms of gender, age, place of living and birth. The examinees
      completed questionnaires to determine variables related to development of enamel
      defects in first permanent molars and permanent incisors. Clinical consequences
      were analyzed by comparing DMFT and treatment needs. The relationship between the
      number of affected teeth in maxillas and mandibles and any relationship between
      right and left side of the jaw was also analyzed. Results were analyzed using:
      percentages, arithmetic mean value, standard deviation, chi- square test, T-test
      2 independent samples, T test for proportion, Pearson correlation, Mann-Whitney U
      test, multiple regression analyses. RESULTS: The prevalence of MIH among the 12
      year-old children was 12.3%. An equal number of male and female were affected.
      The average number of affected teeth among children with MIH was 5.59 (SD+/-2)
      out of which 3.16 (SD+/-1) were the first permanent molars. The research revealed
      demographic predisposition to MIH. The examinees with MIH suffered more often
      from various diseases, particularly from tonsillitis and illnesses accompanied
      with high fever. With the exception of tonsillectomy, variables did not appear to
      be related to MIH. CONCLUSIONS: Based on the information about the early
      childhood illnesses and using multiple regression analyses, it was not possible
      to make a reliable prediction, whether or not a person would develop MIH. There
      is a clear need for further studies focused on aetiological factors in order to
      understand the development of MIH and adopt preventive measures for this
      clinically demanding condition.

PMID- 18076850
TI  - Enamel mineral concentration in diabetic rodents.
AB  - AIM: This was to use x-ray microtomography (XMT), to assess the mineral
      composition and 3-D structure of enamel and bone in the teeth and skulls of
      diabetic rodents. METHODS: Three-dimensional images of the skull were
      reconstructed using computer generated false colour to highlight different levels
      of mineralization in bone and enamel. RESULTS: These showed that diabetic rodents
      exhibited more wear in their teeth. Deformities were observed in the alveolar
      process of the mandible and maxilla. Regions of extensive hypomineralization were
      found in the calvarial bone of skulls. The maximum mineral concentrations and the
      time constants for diabetic rodents were similar to the controls. The diabetic
      mice appeared to have random regions of hypomineralization and one diabetic rat
      had areas of hypoplasia in the mandibular incisors. CONCLUSIONS: Diabetes may
      have a detrimental influence on the function of ameloblasts in laying down
      enamel.

PMID- 18076851
TI  - Comparison between a simplified and a conventional biofilm index in relation to
      caries activity and gingivitis in the primary dentition.
AB  - AIM: This was to compare a simplified biofilm index with a conventional one in
      relation to caries activity and gingivitis in the primary dentition. STUDY
      DESIGN: Observational, cross-sectional. METHODS: The sample consisted of 90
      children aged 10 to 57 months-old. A single examiner performed all examinations.
      Two visible biofilm indices, one simplified (BF1) and the other conventional
      (BF2), were used. Gingival bleeding was assessed after flossing all proximal
      surfaces and each tooth surface was classified for caries, including non
      cavitated lesions. RESULTS: According to BF1, half of the sample (45 - 50%) had
      thick biofilm. BF2 showed a mean value of 21.8% (SD+/-16.5); 12 (13.3%) children
      had gingival bleeding and the mean percentage of bleeding surfaces was 0.9% (SD+/
      2.5). Caries was present in 36 (40.0%) children and the mean value of active
      lesions was 2.1 (SD+/-4.3). The association between visible biofilm and gingival
      bleeding was significant (p=0.01), except when BF1 was associated with the
      gingival index (p=0.08). The association between BF1 and BF2 with caries activity
      was highly significant (p<0.001). CONCLUSION: Both biofilm indices may be used
      when the outcome being measured is caries. In the primary dentition, though, the
      conventional index (BF2) is better suited for studies about gingivitis.

PMID- 18076852
TI  - Dental caries pattern and predisposing oral hygiene related factors in Nigerian
      preschool children.
AB  - AIM: To determine the pattern of caries in Nigerian pre-school children and to
      identify the effect of age, gender, socio-economic status, oral hygiene status,
      tools used in tooth cleaning and the frequency of tooth cleaning on the
      children's caries experience. METHOD: A cross sectional study involving children
      between the ages of 6 and 71 months with a questionnaire was administered to
      elicit socio-demographic information on each child. Information was also provided
      about the type of oral hygiene tool used by each child and the frequency of tooth
      cleaning each day. An intra-oral examination was conducted to assess dental
      caries (dmft) and oral hygiene status. A diagnosis of rampant caries, caries or
      no caries was also made. STATISTICS: Logistic regression was used to assess the
      effect of age, socioeconomic status, gender, birth rank, tooth cleansing methods,
      tooth cleansing frequency, tooth cleansing tool and oral hygiene status on the
      occurrence of rampant, molar and maxillary anterior caries of each study subject.
      RESULTS: Forty one (10.5%) of the 389 preschool children examined had caries. The
      odds a second mandibular primary molar being carious was 4 times greater than
      having a second maxillary molar carious. The age and oral hygiene status had
      significant impact on the dmft. Also the odds of having rampant caries increasing
      almost 4 fold with every score increase in oral hygiene status. CONCLUSIONS:
      There appears to be no significant age related caries distribution pattern in
      Nigerian preschool children. The second primary molars appear to be more
      susceptible to caries in preschool children in Nigeria. The oral hygiene status
      appears to be a risk factor for rampant caries in these children.

PMID- 18076853
TI  - Short communication: dental anxiety levels and outcomes of care: a preliminary
      report on experiences of a sedation assessment clinic.
AB  - AIM: This was twofold: (1) to report on the type of paediatric patient referred
      to the sedation assessment clinic at the Glasgow Dental Hospital and School, and
      (2) to report on the level of anxiety. METHODS: This was a two-part study. The
      first part was a retrospective review of case notes to evaluate referral pathways
      to and from the sedation assessment clinic with regard to a range of variables.
      The second part was a prospective clinical report of dental anxiety. RESULTS: It
      was noted that 31 (67.4%) of patients were initially referred by their general
      dental practitioner, 7 (15.2%) by community dental surgeons and 8 (17.4%) by
      hospital dental surgeons. At the initial referral, 4 children (9%) showed
      symptoms of pain. The majority of patients were from lower social economic areas,
      as determined by DEPCAT score and exhibiting moderate to high anxiety levels. The
      children who were referred for general anaesthesia had the highest anxiety
      scores. Out of a total of 46 patients, five failed to complete treatment within
      the modality laid out for them at the assessment clinic. CONCLUSIONS: (1) The
      patients attending the newly established sedation assessment clinic were mainly
      high caries risk, socially deprived patients and (2) that the majority of
      patients were dentally anxious, the most anxious appearing to have been referred
      for treatment under general anaesthesia.

PMID- 18076854
TI  - The dental management of five paediatric patients with a history of acute
      intermittent porphyria.
AB  - BACKGROUND: Acute Intermittent Porphyria (AIP) is a rare autosomal dominant
      metabolic disorder resulting from partial deficiency of porphobobilinogen
      deaminase, the third enzyme of the haem synthetic pathway. Patients with AIP may
      be vulnerable to acute neurovisceral attacks if exposed to certain drugs,
      including some drugs used in dental practice. CASE REPORTS: This article outlines
      the dental management of 5 children with a diagnosis of latent AIP or a family
      history of AIP. The local analgesic agent used in all cases was bupivacaine or
      levobupivacaine. Nitrous oxide and oxygen inhalation sedation was used in 2 cases
      and general anaesthesia, using propofol, isoflurane with nitrous oxide and
      oxygen, was used in another case. The dental treatment undertaken included
      restorations, endodontics and extractions. CONCLUSION: Dental treatment using
      bupivacaine or levobupivacaine as local analgesic agents was successfully and
      safely provided for 5 children with a diagnosis of latent AIP or a family history
      of AIP.

PMID- 18076855
TI  - Case report: Denys- Drash syndrome.
AB  - BACKGROUND: Denys-Drash Syndrome (DDS) is an uncommon disorder that appears
      sporadically and in rare cases may be inherited as an autosomal dominant trait It
      manifests either at birth or within the first year of life and typically consists
      of the triad of congenital nephropathy, Wilms tumour and intersex disorder. CASE
      REPORT: A 10 year-old Caucasian girl was referred to the Dental Department, at
      Glasgow Royal Hospital for Sick Children by her Paediatric Nephrologist
      Consultant. The patient was being teased by her peers over her markedly
      discoloured teeth. The dental history revealed that the patient was a regular
      dental attendee from an early age. She was dentally anxious having only
      experienced dental treatment under general anaesthesia (GA) when she was 4 years
      old. Apparently her primary dentition also showed a generalised discolouration.
      TREATMENT: This consisted of multiple visits for diet analysis and tooth brushing
      instruction with the use of disclosing tablets. Plaque control significantly
      improved when using a battery operated toothbrush because of its larger handle
      which the patient found easier to use and a 0.05% sodium fluoride mouthwash was
      given for daily use. Dyract(AP) veneers directly bonded onto maxillary permanent
      incisors and mandibular permanent anterior teeth was carried out. This was an
      interim measure to improve the patient's appearance while assessing the patient
      co-operation. The compomer facings were replaced with BelleGlass NG veneers which
      were cemented onto the maxillary incisors and mandibular anterior teeth using
      Adhesive By Choice (ABC) system under rubber dam on two separate visits. FOLLOW
      UP: At her last visit, 27 months after treatment, the patient was still satisfied
      with the restorative treatment. However, further teeth had erupted including all
      the premolars. BelleGlass NG crowns were indicated. It was also decided to
      replace the preformed chrome cobalt crowns with full coverage BelleGlass NG
      crowns.

PMID- 18076856
TI  - Why a burden of disease study?
AB  - From the time I was appointed as Director of the European Centre for Disease
      Prevention and Control (ECDC) in 2005, I and the ECDC Governing and Advisory
      Bodies faced the task of tackling the 46 diseases under mandatory notification in
      the European Union (EU), as well as severe acute respiratory syndrome (SARS),
      avian influenza and West Nile virus.

PMID- 18076857
TI  - Pilot scheme for monitoring sickness absence in schools during the 2006/07 winter
      in England: can these data be used as a proxy for influenza activity?
AB  - During influenza epidemics, school-aged children are amongst the first affected
      patients. They frequently then spread the virus within their families.
      Recognising influenza activity in schools may therefore be an important indicator
      of early activity in the wider community. During 2005/06, influenza B was
      associated with high levels of morbidity in school-children and over 600 schools
      outbreaks were reported to the Health Protection Agency by local Health
      Protection Units. While it is not possible to directly monitor influenza in
      schools, the feasibility and validity of using sentinel school absenteeism data,
      as a proxy for influenza in the community can be investigated. From week 02/07 to
      20/07, eight primary and three secondary schools from five HPA regions were able,
      via the Department of Health-funded Health Protection Informatics website, to
      report daily electronic registration data, relating to absenteeism due to
      illness. Aggregated absenteeism data due to illness peaked the same week as
      indices for the age group comparable to that used by the Royal College for
      General Practitioners and NHS Direct schemes. When illness-defined absenteeism
      data was stratified into primary and secondary schools, absence in primary
      schools peaked one week before that in secondary schools and the established
      schemes for all ages. The start time of the study meant that initial increases in
      activity could not be measured. These encouraging results justify expanding this
      sentinel scheme to collect more rigorous evidence of the usefulness of
      absenteeism as a proxy for influenza activity and a tool to inform policy and
      trigger local responses.

PMID- 18076858
TI  - Risk groups and uptake of influenza and pneumococcal vaccine in Ireland.
AB  - In Ireland, influenza and pneumococcal vaccines are recommended for adults aged
      65 years and over and for those with chronic illness or immunosuppression.
      Influenza vaccine is recommended for healthcare workers (HCWs) and residents of
      long stay care facilities. Influenza vaccine uptake is only available for those
      aged 65 years and over. We conducted a survey to estimate the size of risk groups
      between 18 and 64 years of age, influenza and pneumococcal vaccine uptake in this
      group, and to determine possible factors influencing vaccine uptake to improve
      targeted immunisation programmes. Among respondents aged 18-64 years, 136 of
      1,218 (11%) belonged to a health risk group; uptake of influenza and pneumococcal
      vaccine in these risk groups was 28% (95% CI: 20.9-35.4) and 11% (95% CI: 6.7
      17.2) respectively. Uptake among persons aged over 65 years was 69% (95% CI: 62.2
      74.4) and 41% (95% CI: 35.0-47.9) for influenza and pneumococcal vaccine,
      respectively. Influenza vaccine uptake among HCWs was 20% (95% CI: 13.1-28.7).
      Half (47.6%) of influenza-vaccinated respondents reported that their family
      doctor had recommended it; 60% of non-vaccinated respondents, for whom influenza
      vaccine was indicated, saw themselves at low risk of influenza.

PMID- 18076859
TI  - Meeting report from the Third European Congress of Virology, 1-5 September 2007
      in Nuremberg, Germany.

PMID- 18076860
TI  - The burden of infectious diseases in Europe: a pilot study.
AB  - The main objectives of this pilot study were to test the potential use of the
      disease burden concept in the field of infectious diseases, including data
      quality and availability; to recommend future studies; and to stimulate a debate.
      The disease burden of seven infectious diseases (influenza, measles, HIV,
      campylobacteriosis, infection with enterohaemorrhagic Escherichia coli,
      salmonellosis and tuberculosis) in Europe was estimated by calculating Disability
      Adjusted Life Years (DALYs), a composite measure that attempts to combine
      mortality, incidence and sequelae, taking duration and severity into account. The
      results show that the relative burden of diseases as measured by DALYs differs
      from that only measured by incidence or mortality. Several limitations regarding
      data availability and quality have been identified, resulting in an
      underestimation of the true burden of disease in this pilot. Notwithstanding
      these, HIV-infection, tuberculosis (TB) and influenza are estimated to cause the
      highest burden in Europe among the selected diseases. The burden of foodborne
      diseases (campylobacteriosis, infection with enterohaemorrhagic Escherichia coli
      and salmonellosis) and in particular of measles is lower. A consideration of the
      relative comparison of burden between diseases can be useful when tackling the
      difficult, sensitive but necessary task of identifying priority actions. A low
      burden stresses the need for continued support for prevention and control whereas
      a high burden indicates the need for additional interventions. Following this
      pilot project, a generalised burden of disease study for infectious diseases in
      Europe is recommended. Such a study would benefit from an approach that
      identifies and combines several methods of investigation, including
      epidemiological modelling, and it should be done in collaboration with other
      international efforts in this field.

PMID- 18076861
TI  - Exploration of cost effectiveness of active vaccination in the control of a
      school outbreak of hepatitis A in a deprived community in the United Kingdom.
AB  - In January 2006, an outbreak of hepatitis A occurred in a socio-economically
      deprived area of Liverpool, in the United Kingdom (UK), where extensive community
      outbreaks of hepatitis had previously occurred. A total of nine cases were
      confirmed. Five of these were linked within a primary school. The outbreak
      initially occurred among a close social contact group, but there was evidence of
      subsequent person-to-person transmission within a local primary school. The
      school was attended by 221 pupils (age range 4-12 years) with a total of 37
      teaching and other staff (age range 22-71 years). Following local risk
      assessment, mass hepatitis A virus (HAV) vaccination was offered to all staff and
      pupils, as all were judged to be likely to have been in close contact with the
      affected pupils. A total of 188 of 217 eligible children (87%), and 33 of 37
      staff (89%) were vaccinated. A salivary seroprevalence survey was conducted at
      the same time as vaccination to assess the benefit of this intervention in the
      school population. The survey confirmed high levels of susceptibility to
      hepatitis A in this setting (97.8%, 95% CI 91.6 to 99.62). The direct costs of
      intervention were estimated as euro5,000. The cost effectiveness of intervention
      varies widely (euro60.50 to euro2,099 per case avoided) depending on the expected
      attack rate, which is difficult to estimate due to heterogeneity in published
      studies.

PMID- 18076862
TI  - Legionnaires disease in Europe: 2005-2006.
AB  - Once a year, every country that participates in the European Surveillance Scheme
      for Travel Associated Legionnaires' Disease (EWGLINET) is asked to submit a
      dataset comprising all cases of Legionnaires' disease (not only travel
      associated) with date of onset in the previous year. This paper presents the data
      collected for 2005 and 2006. In this period, 11,980 cases were reported by 35
      countries, showing a continued increase compared with earlier years. 214
      outbreaks or clusters were reported, involving 1028 cases. 377 cases died, giving
      a case fatality rate of 6.6%. The highest incidence rates in both years were
      recorded in Spain, while six countries reported a rate of less than one case per
      million population in at least one of the years. Incidence rates by age group
      were included in the dataset for the first time, showing an increase of the
      overall rate with age. Main method of diagnosis was the urinary antigen test
      (76.0%), whilst the percentage of cases diagnosed by culture fell from 10.0% in
      previous years to 8.9% in 2005-2006.

PMID- 18076863
TI  - DIPNET - establishment of a dedicated surveillance network for diphtheria in
      Europe.
AB  - The ninth international meeting of the European Laboratory Working Group on
      Diphtheria (ELWGD) and the first annual meeting of the Diphtheria Surveillance
      Network (DIPNET) was held in Vouliagmeni, Greece, in November 2006. The
      recognition of DIPNET as an established Dedicated Surveillance Network (DSN) by
      the European Commission (EC) was announced, with the specific objective "to
      establish a Pan-European network of expertise for the prevention of diphtheria
      and other related infections". At the meeting, DIPNET participants from the
      European Union (EU) Member States and associated countries as well as
      collaborators from countries beyond EU presented the current situation concerning
      the clinical, epidemiological and microbiological aspects of diphtheria and
      related infections. Issues highlighted included the need for improving
      surveillance systems, supporting laboratory diagnostics globally, and undertaking
      screening and seroepidemiological studies to sustain diphtheria control in the
      WHO European Region and beyond.

PMID- 18076864
TI  - Effect of 4% titanium tetrafluoride solution on dental erosion by a soft drink:
      an in situ/ex vivo study.
AB  - OBJECTIVE: This in situ/ex vivo study assessed the effect of titanium
      tetrafluoride (TiF(4)) on permanent human enamel subjected to erosion. DESIGN:
      Ten volunteers took part in this study performed in two phases. In the first
      phase (ERO), they wore acrylic palatal appliances containing two enamel blocks,
      divided into two rows: TiF(4) (F) and no-TiF(4) (no-F). During the 1st day, the
      formation of a salivary pellicle was allowed. In the 2nd day, the TiF(4) solution
      was applied on one row (ERO+F), whereas on the other row no treatment was
      performed (ERO+no-F). From 3rd until 7th day, the blocks were subjected to
      erosion, 4x per day. In the 2nd phase (no-ERO), the volunteers wore acrylic
      palatal appliances containing one enamel block, during 2 days, to assess the
      effect of TiF(4) only (no-ERO+F). Enamel alterations were determined using
      profilometry (wear), microhardness (%SMHC) tests, scanning electron microscope
      and microprobe analysis. The %SMHC and wear were tested using ANOVA and Tukey's
      post hoc tests (p<0.05). RESULTS: The mean of %SMHC and wear (microm) values (+/
      S.D.) were, respectively: ERO+F -73.32+/-5.16(A)/2.40+/-0.60(a); ERO+no-F 
      83.49+/-4.59(B)/1.17+/-0.48(b) and no-ERO+F -67.92+/-6.16(A)/0.21+/-0.09(c). In
      microscope analysis, the no-F group showed enamel with honeycomb appearance. For
      F groups, it was observed a surface coating with microcracks. The microprobe
      analysis revealed the presence of the following elements (%) in groups ERO+F,
      ERO+no-F and no-ERO+F, respectively: Ca (69.9, 72.5, 66.25); P (25.9, 26.5,
      26.06); Ti (3.0, 0, 5.93). CONCLUSIONS: The TiF(4) was unable to reduce dental
      erosion.

PMID- 18076865
TI  - Cognitive confidence in obsessive-compulsive disorder: distrusting perception,
      attention and memory.
AB  - Previous studies have established that obsessive-compulsive disorder (OCD) is
      characterised by significant levels of distrust in memory (e.g. for actions).
      Ironically, this lowered confidence is at least in part due to repeated checking,
      which is assumed to lower perceptual processing and thereby reduces vividness and
      detail of the recollections. In a previous study, Hermans, D., Martens, K., De
      Cort, K., Pieters, G., and Eelen, P. [(2003). Reality monitoring and
      metacognitive beliefs related to cognitive confidence in OCD. Behaviour Research
      and Therapy, 41, 383-401] observed that OCD is not only characterised by reduced
      confidence in memory, but also by a similar distrust in attention (Hermans et
      al., 2003). The present study aimed at replicating and extending this finding. It
      was observed (a) that patients suffering from OCD showed less confidence in
      attention and memory than a clinical and a nonclinical control group; (b) that
      confidence in attention was uniquely related to checking behaviour, and (c) that
      repeated checking caused increased levels of distrust in attention. In addition,
      it was observed that cognitive distrust while performing OCD-related actions not
      only extends to attention, but also to perception. It is argued that research on
      metacognition in OCD should move beyond the study of memory.

PMID- 18076866
TI  - Peripheral elevation of IGF-1 fails to alter Abeta clearance in multiple in vivo
      models.
AB  - Increasing beta-amyloid (Abeta) clearance may alter the course of Alzheimer's
      disease progression and attenuate amyloid plaque pathology. Insulin-like growth
      factor I (IGF-1) augmentation has been suggested to increase Abeta clearance by
      facilitating transport of Abeta out of the brain. The availability of safe agents
      that increase IGF-1 levels therefore makes IGF-1 elevation an attractive target
      for disease modifying therapy in AD. The present series of studies sought to
      replicate published paradigms in which peripheral IGF-1 administration lowered
      brain Abeta acutely, with reduction in plaque pathology after chronic treatment.
      Thus Abeta levels were measured in several animal models following treatments
      that elevated IGF-1. Administration of IGF-1 to young or old rats for up to 3
      days had no effect on Abeta levels in brain, CSF, or plasma. In adult beagles, 4
      days of dosing with the growth hormone secretagogue, CP-424391, doubled baseline
      plasma IGF-1 levels, yet failed to alter CSF or plasma Abeta. 5-day treatment of
      young Tg2576 mice with IGF-1 produced robust elevations of IGF-1 levels in
      plasma, but no effects on Abeta were detected in brain, CSF, or plasma. Finally,
      11-month-old Tg2576 mice were implanted with subcutaneous minipumps delivering
      IGF-1 for 1 month. No significant changes in Abeta (by ELISA or Western blot),
      plaque pathology, or phospho-tau epitopes were detected. These results do not
      demonstrate acute or chronic actions of peripherally administered IGF-1 on Abeta
      levels or the phosphorylation state of tau and therefore do not suggest any
      disease-modifying benefits of IGF-1 restorative therapy for AD through these
      mechanisms.

PMID- 18076867
TI  - Binding thermodynamic characterization of human P2X1 and P2X3 purinergic
      receptors.
AB  - The present study was designed to perform binding and thermodynamic
      characterization of human P2X1 and P2X3 purinergic receptors expressed in HEK 293
      cells. The thermodynamic parameters DeltaG degrees , DeltaH degrees and DeltaS
      degrees (standard free energy, enthalpy and entropy) of the binding equilibrium
      of well-known purinergic agonists and antagonists at P2X1 and P2X3 receptors were
      determined. Saturation binding experiments, performed in the temperature range 4
      30 degrees C by using the high affinity purinergic agonist [3H]alphabetameATP,
      revealed a single class of binding sites with an affinity value in the nanomolar
      range in both cell lines examined. The affinity changed with the temperature
      whereas receptor density was essentially independent of it. van't Hoff plots of
      the purinergic receptors were linear in the range 4-30 degrees C for agonists and
      antagonists. The thermodynamic parameters of the P2X1 or P2X3 purinergic
      receptors were in the ranges -31 kJ mol(-1) < or =DeltaH degrees < or =-19 kJ
      mol(-1) and 17 J K(-1) mol(-1)< or =DeltaS degrees < or =51 J K(-1)mol(-1) or -26
      kJ mol(-1)< or =DeltaH degrees < or =36 kJ mol(-1) and 59< or =DeltaS degrees <
      or =249 JK(-1) mol(-1), respectively. The results of these parameters showed that
      P2X1 receptors are not thermodynamically discriminated and that the binding of
      agonists and antagonists was both enthalpy and entropy-driven. P2X3 receptors
      were thermodynamically discriminated and purinergic agonist binding was enthalpy
      and entropy-driven while antagonist binding was totally entropy-driven. The
      analysis of such thermodynamic data makes it possible to obtain additional
      information on the nature of the forces driving the purinergic binding
      interaction. These data could be interesting in drug discovery programs aimed at
      development of novel and potent P2X1 and P2X3 purinergic ligands.

PMID- 18076868
TI  - The interaction of task-relevant and task-irrelevant stimulus features in the
      number/size congruency paradigm: an ERP study.
AB  - We studied whether task-relevant numerical information and task-irrelevant
      physical size information interact during perceptual and/or response processing
      in the number/size congruency paradigm (NSCP). Participants decided which of two
      simultaneously presented numbers was larger numerically. The physical size of
      numbers delivered neutral, congruent, or incongruent information with numerical
      magnitude. Both stimulus- and response-locked event-related brain potentials
      (ERPs) were analyzed. The lateralized readiness potential (LRP) was used for
      indexing motor preparation. Similar early facilitation and interference effects
      appeared in the amplitude of ERPs between 150 and 250 ms after stimulus
      presentation, focused over parieto-occipital electrode-sites. We conclude that
      these effects reflected a similar process in both facilitation and interference,
      related to a general increase of processing load and/or conflict detection.
      Further, we have replicated our former findings demonstrating late facilitation
      and interference effects between 300 and 430 ms. These effects may be related to
      the conflict monitoring and response-selection activity of the anterior cingulate
      cortex, or may be related to higher level contextual analysis. Our findings
      suggest that facilitation and interference effects appear at multiple levels of
      stimulus and response processing. We have also demonstrated ERP amplitude effects
      as a function of numerical difference between the to-be-compared numbers both in
      stimulus- and response-locked ERPs.

PMID- 18076870
TI  - Theta EEG oscillatory activity and auditory change detection.
AB  - The mismatch negativity is an electrophysiological marker of auditory change
      detection in the event-related brain potential and has been proposed to reflect
      an automatic comparison process between an incoming stimulus and the
      representation of prior items in a sequence. There is evidence for two main
      functional subcomponents comprising the MMN, generated by temporal and frontal
      brain areas, respectively. Using data obtained in an MMN paradigm, we performed
      time-frequency analysis to reveal the changes in oscillatory neural activity in
      the theta band. The results suggest that the frontal component of the MMN is
      brought about by an increase in theta power for the deviant trials and, possibly,
      by an additional contribution of theta phase alignment. By contrast, the temporal
      component of the MMN, best seen in recordings from mastoid electrodes, is
      generated by phase resetting of theta rhythm with no concomitant power
      modulation. Thus, frontal and temporal MMN components do not only differ with
      regard to their functional significance but also appear to be generated by
      distinct neurophysiological mechanisms.

PMID- 18076869
TI  - Exploring the neuroprotective effects of modafinil in a marmoset Parkinson model
      with immunohistochemistry, magnetic resonance imaging and spectroscopy.
AB  - Neuroprotective therapeutics stop or slow down the degeneration process in animal
      models of Parkinson's disease (PD). Neuronal survival in PD animal models is
      often measured by immunohistochemistry. However, dynamic changes in the pathology
      of the brain cannot be explored with this technique. Application of proton
      magnetic resonance (MR) imaging (MRI) and spectroscopy (MRS) can cover this
      lacuna as these techniques are non-invasive and can be repeated over time in the
      same animal. Therefore, the sensitivity of both techniques to measure changes in
      PD-pathology was explored in an experiment studying the neuroprotective effects
      of the vigilance enhancer modafinil in a marmoset PD model. Eleven marmoset
      monkeys were treated with the neurotoxin 1-methyl-1,2,3,6-tetrahydropyridine
      (MPTP). Six of these 11 animals, simultaneously, received a daily oral dose of
      modafinil (100 mg/kg) and five received vehicle for 27 days. MR experiments were
      performed at baseline and 1 and 3.5 weeks after the MPTP intoxication period
      after which brains were analyzed with immunohistochemistry. Tyrosine hydroxylase
      immunoreactive (TH-IR) staining of dopamine neurons of the substantia nigra pars
      compacta confirmed that modafinil was able to partially prevent the MPTP-induced
      neuronal damage. In MRS, N-acetylaspartate (NAA)/phosphocreatine (tCR) ratios
      confirmed the protective effect indicating that this is a sensitive measure to
      detect neuroprotection in the MPTP marmoset model. Furthermore, the number of TH
      IR positive neurons and the NAA/tCR ratio were significantly correlated to
      behavioral observations indicating that the changes measured in the brain are
      also reflected in the behavior and vice versa.

PMID- 18076871
TI  - Quercus infectoria galls possess antioxidant activity and abrogates oxidative
      stress-induced functional alterations in murine macrophages.
AB  - The present study reports the antioxidant activity of ethanolic extract of
      Quercus infectoria galls. The antioxidant potency of galls was investigated
      employing several established in vitro model systems. Their protective efficacy
      on oxidative modulation of murine macrophages was also explored. Gall extract was
      found to contain a large amount of polyphenols and possess a potent reducing
      power. HPTLC analysis of the extract suggested it to contain 19.925% tannic acid
      (TA) and 8.75% gallic acid (GA). The extract potently scavenged free radicals
      including DPPH (IC(50)~0.5 microg/ml), ABTS (IC(50)~1 microg/ml), hydrogen
      peroxide (H(2)O(2)) (IC(50)~2.6 microg/ml) and hydroxyl (*OH) radicals (IC(50)~6
      microg/ml). Gall extract also chelated metal ions and inhibited Fe(3+) -ascorbate
      induced oxidation of protein and peroxidation of lipids. Exposure of rat
      peritoneal macrophages to tertiary butyl hydroperoxide (tBOOH) induced oxidative
      stress in them and altered their phagocytic functions. These macrophages showed
      elevated secretion of lysosomal hydrolases, and attenuated phagocytosis and
      respiratory burst. Activity of macrophage mannose receptor (MR) also diminished
      following oxidant exposure. Pretreatment of macrophages with gall extract
      preserved antioxidant armory near to control values and significantly protected
      against all the investigated functional mutilations. MTT assay revealed gall
      extract to enhance percent survival of tBOOH exposed macrophages. These results
      indicate that Q. infectoria galls possess potent antioxidant activity, when
      tested both in chemical as well as biological models.

PMID- 18076872
TI  - An effect of spatial-temporal association of response codes: understanding the
      cognitive representations of time.
AB  - The present study addresses the question of how such an abstract concept as time
      is represented by our cognitive system. Specifically, the aim was to assess
      whether temporal information is cognitively represented through left-to-right
      spatial coordinates, as already shown for other ordered sequences (e.g.,
      numbers). In Experiment 1, the task-relevant information was the temporal
      duration of a cross. RTs were shorter when short and long durations had to be
      responded to with left and right hands, respectively, than with the opposite
      stimulus-response mapping. The possible explanation that the foreperiod effect
      (i.e., shorter RTs for longer durations) is greater with right than with left
      hand responses is discarded by results of Experiment 2, in which right and left
      hand responses alternated block-wise in a variable foreperiod paradigm. Other
      explanations concerning manual or hemispheric asymmetries may be excluded based
      on the results of control experiments, which show that the compatibility effect
      between response side and cross duration occurs for accuracy when responses are
      given with crossed hands (Experiment 3), and for RTs when responses are given
      within one hand (Experiment 4). This pattern suggests that elapsing time,
      similarly to other ordered information, is represented in some circumstances
      through an internal spatial reference frame, in a way that may influence motor
      performance. Finally, in Experiment 5, the temporal duration was parametrically
      varied using different values for each response category (i.e., 3 short and 3
      long durations). The compatibility effect between hand and duration was
      replicated, but followed a rectangular function of the duration. The shape of
      this function is discussed in relation to the specific task demands.

PMID- 18076873
TI  - The tonal function of a task-irrelevant chord modulates speed of visual
      processing.
AB  - Harmonic priming studies have provided evidence that musical expectations
      influence sung phoneme monitoring, with facilitated processing for phonemes sung
      on tonally related (expected) chords in comparison to less-related (less
      expected) chords [Bigand, Tillmann, Poulin, D'Adamo, and Madurell (2001). The
      effect of harmonic context on phoneme monitoring in vocal music. Cognition, 81,
      B11-B20]. This tonal relatedness effect has suggested two interpretations: (a)
      processing of music and language interact at some level of processing; and (b)
      tonal functions of chords influence task performance via listeners' attention.
      Our study investigated these hypotheses by exploring whether the effect of tonal
      relatedness extends to the processing of visually presented syllables
      (Experiments 1 and 2) and geometric forms (Experiments 3 and 4). For Experiments
      1-4, visual target identification was faster when the musical background
      fulfilled listeners' expectations (i.e., a related chord was played
      simultaneously). In Experiment 4, the addition of a baseline condition (i.e.,
      without an established tonal center) further showed that the observed difference
      was due to a facilitation linked to the related chord and not to an inhibition or
      disruption caused by the less-related chord. This outcome suggests the influence
      of musical structures on attentional mechanisms and that these mechanisms are
      shared between auditory and visual modalities. The implications for research
      investigating neural correlates shared by music and language processing are
      discussed.

PMID- 18076874
TI  - Effects of tanshinone VI on phosphorylation of ERK and Akt in isolated
      cardiomyocytes and cardiac fibroblasts.
AB  - Effects of tanshinone VI, a diterpene from Tan-Shen, on humoral factor-induced
      phosphorylation of ERK and Akt during hypertrophy of cardiomyocytes and fibrosis
      of cardiac fibroblasts isolated from neonatal rats were examined. Treatment of
      cultured cardiomyocytes with 10 nM insulin-like growth factor-1 (IGF-1) or 10 nM
      endothelin-1 resulted in an increase in leucine incorporation into acid-insoluble
      fraction. Treatment of cultured cardiac fibroblasts with 10 nM IGF-1 or 10 nM
      angiotensin II increased incorporation of proline. IGF-1 increased phosphorylated
      extracellular signal-regulated kinase (pERK) and protein kinase B (pAkt) of
      cardiomyocytes, whereas endothelin-1 increased pERK, but not pAkt. Treatment of
      cardiac fibroblasts with 10 nM IGF-1 or 10 nM angiotensin II also increased pERK,
      whereas pAkt was increased by treatment with IGF-1 alone. When the cardiomyocytes
      were incubated in the presence of 10 microM tanshinone VI, IGF-1- and endothelin
      1-induced increases in pERK, but not pAkt, were partially attenuated. Treatment
      of cardiac fibroblasts with 10 microM tanshinone VI also attenuated IGF-1-induced
      increases in pERK and pAkt. Tanshinone VI also partially attenuated angiotensin
      II-induced increase in proline incorporation into cardiac fibroblasts. PD98059,
      an inhibitor for phosphorylation of extracellular signal-regulated kinase (ERK),
      but not wortmannin, that for protein kinase B phosphorylation, attenuated an
      increase in leucine incorporation into cardiomyocytes in the presence of either
      IGF-1 or endothelin-1. These results suggest that tanshinone VI is a possible
      agent that can attenuate the humoral factor-induced hypertrophy of cardiomyocytes
      and fibrosis of cardiac fibroblasts via an attenuation of ERK phosphorylation in
      these cells.

PMID- 18076875
TI  - Dose-dependent beneficial hemodynamic effects of BAY 41-2272 in a canine model of
      acute pulmonary thromboembolism.
AB  - The current therapy of acute pulmonary embolism is focused on removing the
      mechanical obstruction of the pulmonary vessels. However, accumulating evidence
      suggests that pulmonary vasoconstriction drives many of the hemodynamic changes
      found in this condition. We examined the effects of stimulation of soluble
      guanylate cyclase with BAY 41-2272 (5-Cyclopropyl-2-[1-(2-fluoro-benzyl)-1H
      pyrazolo[3,4-b]pyridin-3-yl]-pyrim idin-4-ylamine) in an anesthetized dog model
      of acute pulmonary embolism. Hemodynamic and arterial blood gas evaluations were
      performed in non-embolized dogs treated with vehicle (N=5), and in embolized dogs
      (intravenous injections of microspheres) that received BAY 41-2272 intravenously
      in doses of 0.03, 0.1, 0.3, and 1 mg/kg/h or vehicle (1 ml/kg/h of 1.13% ethanol
      in saline, volume/volume). Plasma cGMP and thiobarbituric acid reactive
      substances concentrations were determined using a commercial enzyme immunoassay
      and a fluorometric method, respectively. The infusion of BAY 41-2272 resulted in
      a decrease in pulmonary artery pressure by approximately 29%, and in pulmonary
      vascular resistance by approximately 46% of the respective increases induced by
      lung embolization (both P<0.05). While the higher doses of BAY 41-2272 produced
      no additional effects on the pulmonary circulation, they caused significant
      arterial hypotension and reduction in systemic vascular resistance (both P<0.05).
      Although BAY 41-2272 increased cGMP concentrations (P<0.05), it did not affect
      the hypoxemia and the increased oxidative stress caused by lung embolization.
      These results suggest that stimulation of soluble guanylate cyclase with low (but
      not high) doses of BAY 41-2272 produces selective pulmonary vasodilation during
      acute pulmonary embolism. The dose-dependent systemic effects produced by BAY 41
      2272, however, may limit its usefulness in larger doses.

PMID- 18076876
TI  - Interaction between the homeodomain protein HOXC13 and ETS family transcription
      factor PU.1 and its implication in the differentiation of murine erythroleukemia
      cells.
AB  - Some of homeodomain proteins and the ETS family of transcription factors are
      involved in hematopoiesis. RT-PCR analysis revealed that the HOXC13 and PU.1
      genes were expressed in murine erythroleukemia (MEL) cells and their levels
      decreased during DMSO-induced differentiation into erythroid cells. HOXC13 bound
      to the ETS domain of PU.1 through a region encompassing the C-terminal part of
      the homeodomain and the most C-terminal region and enhanced the transcriptional
      activity of PU.1. Enforced expression of HOXC13 in MEL cells resulted in the
      suppression of beta-globin gene expression. In MEL cells overexpressing HOXC13
      and PU.1, which also inhibits the differentiation of MEL cells, no synergistic
      effect on the suppression of beta-globin gene expression was observed. However,
      in the presence of DMSO, the expression levels of the beta-globin gene in the
      cells overexpressing HOXC13 and PU.1 were, unexpectedly, higher than those in the
      cells overexpressing PU.1 alone. The levels of PU.1 protein were markedly
      decreased despite that the levels of mRNA were preserved in the cells
      overexpressing PU.1 and HOXC13. It was, thus, suggested that although HOXC13
      negatively regulates the differentiation of MEL cells into erythroid cells, it
      antagonizes PU.1 possibly by down-regulation of PU.1 protein in the presence of a
      differentiation stimulus.

PMID- 18076877
TI  - High frequency stimulation and temporary inactivation of the subthalamic nucleus
      reduce quinpirole-induced compulsive checking behavior in rats.
AB  - Obsessive-compulsive disorder (OCD) represents a highly prevalent and impairing
      psychiatric disorder. Functional and structural imaging studies implicate the
      involvement of basal ganglia-thalamo-cortical circuits in the pathophysiology of
      this disorder. In patients remaining resistant to pharmaco- and behavioral
      therapy, modulation of these circuits may consequently reverse clinical symptoms.
      High frequency stimulation (HFS) of the subthalamic nucleus (STN), an important
      station of the basal ganglia-thalamo-cortical circuits, has been reported to
      reduce obsessive-compulsive symptoms in a few Parkinson's disease patients with
      comorbid OCD. The present study tested the effects of bilateral HFS of the STN
      and of bilateral pharmacological inactivation of the STN (via intracranial
      administration of the GABA agonist muscimol) on checking behavior in the
      quinpirole rat model of OCD. We demonstrate that both HFS and pharmacological
      inactivation of the STN reduce quinpirole-induced compulsive checking behavior.
      We conclude that functional inhibition of the STN can alleviate compulsive
      checking, and suggest the STN as a potential target structure for HFS in the
      treatment of OCD.

PMID- 18076878
TI  - Quiescent adult neural stem cells are exceptionally sensitive to cosmic
      radiation.
AB  - Generation of new neurons in the adult brain, a process that is likely to be
      essential for learning, memory, and mood regulation, is impaired by radiation.
      Therefore, radiation exposure might have not only such previously expected
      consequences as increased probability of developing cancer, but might also impair
      cognitive function and emotional stability. Radiation exposure is encountered in
      settings ranging from cancer therapy to space travel; evaluating the neurogenic
      risks of radiation requires identifying the at-risk populations of stem and
      progenitor cells in the adult brain. Here we have used a novel reporter mouse
      line to find that early neural progenitors are selectively affected by conditions
      simulating the space radiation environment. This is reflected both in a decrease
      in the number of these progenitors in the neurogenic regions and in an increase
      in the number of dying cells in these regions. Unexpectedly, we found that
      quiescent neural stem cells, rather than their rapidly dividing progeny, are most
      sensitive to radiation. Since these stem cells are responsible for adult
      neurogenesis, their death would have a profound impact on the production of new
      neurons in the irradiated adult brain. Our finding raises an important concern
      about cognitive and emotional risks associated with radiation exposure.

PMID- 18076879
TI  - Transient transfection of purified Babesia bovis merozoites.
AB  - Transient transfection of intraerythrocytic Babesia bovis parasites has been
      previously reported. In this study, we describe the development and optimization
      of methods for transfection of purified B. bovis merozoites using either
      nucleofection (Amaxa) or conventional electroporation (Gene Pulser II, BioRad).
      Initially, the optimal buffer ("Plasmodium 88A6") and program (v-24) for
      nucleofection of free merozoites with a plasmid containing the luciferase gene as
      a reporter were determined. Using the same reporter plasmid, optimal voltage,
      capacitance and resistance for transfecting free merozoites by electroporation
      were defined to be 1.2 kV/25 microF/200 Omega. Using these optimal parameters,
      analysis of the time course of luciferase expression using either system to
      transfect free B. bovis merozoites showed high enzyme activity at 24h, with a
      rapid decline thereafter. Nucleofection was approximately five times more
      effective than electroporation when using a small quantity (2 microg) of DNA,
      while electroporation was twice as effective as nucleofection when a larger
      quantity of plasmid DNA (100 microg) was used. Parasite viability was
      significantly higher when using nucleofection when compared to electroporation
      regardless of the amount of DNA used. Comparison of luciferase expression after
      transfection of merozoites with circular, linearized, or double digested plasmid
      indicated that intact, circular plasmid was necessary for optimal luciferase
      expression. Overall, the results provide a basis for optimal transfection of
      purified B. bovis merozoites using either nucleofection or conventional
      electroporation. However, nucleofection is significantly more efficient when
      transfecting either circular or restriction digested DNA in the 2-10 microg
      range.

PMID- 18076880
TI  - A healthy live birth after successful preimplantation genetic diagnosis for
      carriers of complex chromosome rearrangements.
AB  - OBJECTIVE: To report a live birth after successful preimplantation genetic
      diagnosis (PGD) for carriers of complex chromosomal rearrangements (CCRs) with
      translocation and deletion. DESIGN: Fluorescent in situ hybridization (FISH) was
      applied to PGD for CCR carriers. SETTING: University-based centers for
      reproductive medicine. PATIENT(S): Three CCR carriers, patient A with
      46,XX,t(6;10;8)(q25.1;q21.1;q21.1), patient B with
      46,X,del(X)(p22.3),t(2;18)(q14.1;q21)[48]/45,X, t(2;18)(q14.1;q21)[12], and
      patient C with 46,XY,t(5;13;8)(q21.2;q14.3;q24.3). INTERVENTION(S): Balanced or
      normal embryos were diagnosed by PGD and transferred. MAIN OUTCOME MEASURE(S):
      Diagnosis rate of FISH, pregnancy outcome, and karyotype of amniocentesis.
      RESULT(S): Blastomeres were biopsied from 56 embryos in four PGD cycles, and 54
      embryos (96.4%) were successfully diagnosed by FISH. Among them, four embryos
      were diagnosed as transferable in two cycles of patient B and one cycle of
      patient C. After three cycles of embryo transfer, a pregnancy was achieved in the
      second PGD cycle of patient B, and the karyotype of amniocentesis was
      46,XY,t(2;18)(q14.1;q21). A healthy baby was delivered at 40 weeks of gestation
      by cesarean section. CONCLUSION(S): This is the first report for a live birth
      after PGD in the CCR carriers associated with translocation and deletion,
      46,X,del(X)(p22.3),t(2;18)(q14.1;q21)[48]/45,X,t(2;18)(q14.1;q21)[12].
      Preimplantation genetic diagnosis for CCRs needs more consideration and advanced
      techniques for full karyotyping.

PMID- 18076881
TI  - Point- and frequency-specific response of the testicular artery to abdominal
      electroacupuncture in humans.
AB  - OBJECTIVE: To clarify the role of the abdominal acupuncture points and the
      frequency of short-term electroacupuncture (EA) stimulation on testicular blood
      flow (TBF) in humans. DESIGN: A prospective, randomized study. SETTING:
      University hospital, Department of Radiology, ultrasound unit. PATIENT(S): Eighty
      healthy male volunteers were randomly allocated to three groups in stage one and
      to a single group in stage two. In the first stage of the study, the abdominal
      acupuncture points ST-29 (guilai) were stimulated using simple needle insertion,
      2 Hz burst EA or 10 Hz EA, in three different groups. In the second stage of the
      study, abdominal acupuncture points ST-25 (tianshu) were stimulated with the
      frequency found to be more effective in stage one. Stimulation was for 5 minutes
      in each group. INTERVENTION(S): Electroacupuncture and Doppler flowmeter. MAIN
      OUTCOME MEASURE(S): Four groups were compared for volume flow and other related
      parameters of TBF. RESULT(S): The 10-Hz EA stimulation of ST-29 (guilai)
      increased TBF, but simple needle insertion and 2-Hz burst stimulation did not.
      The 10-Hz EA stimulation of ST-25 (tianshu) did not result in significant changes
      in TBF. CONCLUSION(S): For the first time point- and frequency-specific effects
      of abdominal EA on TBF are shown in humans. Further investigation is required to
      ascertain whether these findings may be helpful in the clinical treatment of
      infertile men.

PMID- 18076882
TI  - The nucleus para-retroambiguus: a new group of estrogen receptive cells in the
      caudal ventrolateral medulla of the female golden hamster.
AB  - Receptive female hamsters display very rigid lordotic postures. Estradiol
      facilitates this behavior via activation of estrogen receptors. In the hamster
      brainstem estrogen receptor-alpha-immunoreactive neurons (ER-alpha-IR) are
      present in various brainstem regions including nucleus retroambiguus (NRA) in the
      caudal ventrolateral medulla (CVLM) and nucleus of the solitary tract. ER-alpha
      IR neurons in the CVLM project to the thoracic and upper lumbar cord. However, A1
      neurons in this region do not project to the spinal cord, in contrast to
      overlapping C1 neurons. The question now arises: are ER-alpha-IR cells in the
      CVLM part of the A1/C1 group, or do they belong to the NRA or do they compose a
      separate cluster. A study in ovariectomized female hamsters using a combination
      of double immunostaining and retrograde tracing techniques and measurement of
      soma diameters was carried out. The results showed that A1/C1 neurons in the CVLM
      are almost never ER-alpha-positive; neurons inside or bordering the NRA can be
      divided in two different types: large multipolar and small; the large NRA
      neurons, projecting caudally, are neither tyrosine hydroxylase- (TH) nor ER-alpha
      IR; the small neurons, bordering the NRA and projecting caudally, are ER-alpha-IR
      but not TH-IR. From the available evidence and the present findings it can be
      concluded that the group of small ER-alpha-IR neurons in the CVLM has to be
      considered as a distinct entity, probably involved in the autonomic physiological
      changes concurring with successive phases of the estrous cycle. Because the
      location is closely related to the NRA itself the nucleus is called nucleus para
      retroambiguus, abbreviated (NPRA).

PMID- 18076883
TI  - Effects of motherhood on physiological and subjective responses to infant cries
      in teenage mothers: a comparison with non-mothers and adult mothers.
AB  - The present study was designed to determine whether becoming a mother during the
      adolescent period changes maternal responsiveness or maternal motivation,
      assessed through hormonal, autonomic, and hedonic responses to recorded infant
      cries and interactions with their babies. Fifty-six teen mothers were compared to
      58 teen non-mothers and 49 adult mothers. Teen mothers reported more sympathy and
      alertness in response to recorded infant cries compared to non -mother teens;
      however, among the teen women there were no differences between mothers and non
      mothers in heart rate and cortisol responses to infant cries. In contrast, in
      comparison to adult mothers, teen mothers reported the same levels of sympathy
      and alertness to infant cries; however, adult mothers showed an 'alerted' pattern
      of heart rate and cortisol response to infant cries not seen in the teen mother
      group. Inclusion of the covariate, fathers' employment classification as an index
      of SES or time of testing and cortisol sampling did not affect this pattern of
      results. Taken together, these results show that where self-report is used as a
      measure of maternal responsiveness, teen mothers are no different in
      responsiveness than adult mothers; however, where physiological and interactional
      measures of responsiveness are considered, teen mothers are less likely to show
      heightened or selective responses to infant cries or respond 'attentively' to the
      infant.

PMID- 18076884
TI  - Social stressors and coping mechanisms in wild female baboons (Papio hamadryas
      ursinus).
AB  - We examined the social correlates of fecal glucocorticoid (GC) levels in wild
      female baboons during a period of social and demographic stability. Females' GC
      levels were not affected by individual attributes such as number of kin or
      dominance rank, nor could we detect any significant seasonal effects. Instead, GC
      levels were influenced by behavioral attributes that varied between individuals
      and within individuals across time. Pregnant and cycling females who received
      high rates of aggression had higher GC levels than others. In contrast, pregnant
      and cycling females who received grunts - vocal signals of benign intent - at
      high frequencies from dominant females had lower GC levels than females who
      received grunts at lower frequencies. Lactating females showed the opposite
      trend, apparently as a consequence of the high rate of grunting and intense,
      unsolicited attention that their infants received from others. All females
      experienced lower GC levels in months when they concentrated their grooming among
      a small number of partners than when their grooming was more evenly distributed
      among many partners. Although GC levels in female baboons are most strongly
      influenced by events that directly affect their reproductive success, subtle
      social factors associated with the loss of predictability and control also seem
      to exert an effect. Loss of control may be mitigated if a female is able to
      predict others' intentions - for example, if others grunt to her to signal their
      intentions - and if she is able to express some preference over the timing and
      identities of her grooming partners.

PMID- 18076886
TI  - Endothelial dysfunction: a key to the pathophysiology and natural history of
      peripheral arterial disease?
AB  - Dysfunctional endothelium plays a crucial role in all stages of atherosclerosis
      and thus the accurate assessment of this organ is a valuable tool, especially if
      such assessments are clinically relevant. In peripheral arterial disease (PAD),
      which affects about 27 million of individuals in Europe and North America,
      increased plasma markers of endothelial dysfunction and reduced endothelium
      mediated vasoreactivity, are associated with both the severity and the extent of
      atherosclerosis in the arteries of the lower limbs, is exacerbated by acute
      exercise, may help identify subjects with subclinical coronary artery disease,
      and portends a worse outcome. As a result, endothelial dysfunction is a promising
      target for therapeutic interventions in PAD. Large clinical trials are needed to
      verify whether affected individuals with depressed endothelial function benefit
      from specific treatments.

PMID- 18076885
TI  - Perceptions of pregnancy complications in Haiti.
AB  - OBJECTIVE: To determine the incidence of perceived pregnancy complications and
      associated factors. METHODS: During a census, 450 women identified themselves as
      pregnant and 388 were interviewed postpartum. RESULTS: Complications were
      reported by 58.6%. Bleeding post-delivery was the most frequent complication
      (42.5%), followed by great pain (33.8%), bleeding during pregnancy (20.1%), and
      fever post-delivery (11.6%). Prenatal care at either a dispensary or a clinic was
      associated with reports of bleeding during pregnancy (odds ratio [OR] 9.06; 95%
      confidence interval [CI], 1.71-48.00 and OR 7.58; 95% CI, 1.53-37.48,
      respectively). Women who visited a doctor were less likely to report bleeding
      during pregnancy (OR 0.20; 95% CI, 0.08-0.55) or fever post-delivery (P=0.015).
      Herb use was associated with reported bleeding during pregnancy (OR 2.22; 95% CI,
      1.12-4.40) and great pain (OR 1.94; 95% CI, 1.05-3.58). CONCLUSION: The perceived
      pregnancy complication rate in Haiti is high and is associated with access to
      health care. The association between use of herbs and pregnancy complications
      warrants investigation.

PMID- 18076887
TI  - Modeling the onset and propagation of trabecular bone microdamage during low
      cycle fatigue.
AB  - Relatively small amounts of microdamage have been suggested to have a major
      effect on the mechanical properties of bone. A significant reduction in
      mechanical properties (e.g. modulus) can occur even before the appearance of
      microcracks. This study uses a novel non-linear microdamaging finite-element (FE)
      algorithm to simulate the low-cycle fatigue behavior of high-density trabecular
      bone. We aimed to investigate if diffuse microdamage accumulation and concomitant
      modulus reduction, without the need for complete trabecular strut fracture, may
      be an underlining mechanism for low-cycle fatigue failure (defined as a 30%
      reduction in apparent modulus). A microCT constructed FE model was subjected to a
      single cycle monotonic compression test, and constant and variable amplitude
      loading scenarios to study the initiation and accumulation of low-cycle fatigue
      microdamage. Microcrack initiation was simulated using four damage criteria: 30%,
      40%, 50% and 60% reduction in bone element modulus (el-MR). Evaluation of
      structural (apparent) damage using the four different tissue level damage
      criteria resulted in specimen fatigue failure at 72, 316, 969 and 1518 cycles for
      the 30%, 40%, 50% and 60% el-MR models, respectively. Simulations based on the
      50% el-MR model were consistent with previously published experimental findings.
      A strong, significant non-linear, power law relationship was found between cycles
      to failure (N) and effective strain (Deltasigma/E(0)): N=1.394x10(
      25)(Deltasigma/E(0))(-12.17), r(2)=0.97, p<0.0001. The results suggest that
      microdamage and microcrack propagation, without the need for complete trabecular
      strut fracture, are mechanisms for high-density trabecular bone failure.
      Furthermore, the model is consistent with previous numerical fatigue simulations
      indicating that microdamage to a small number of trabeculae results in relatively
      large specimen modulus reductions and rapid failure.

PMID- 18076888
TI  - Arches of the hand in reach to grasp.
AB  - Topographically, the hand is described by its anterior (palmar) and posterior
      (dorsal) surfaces that encompass a hollow cavity that changes its shape during
      hand preshaping and grasping according to the object to be grasped. The hollow
      cavity has been described as consisting of three arches that run in different
      directions: transverse, longitudinal and oblique, spanning the anterior surface
      of the hand. Although described anatomically, the modulation in the palmar arches
      has not been investigated kinematically during actual grasping. In this study, we
      describe and compare biomechanical formulations of the palmar arch, specifically,
      the distal transverse and the oblique arches. In addition, we introduce another
      biomechanical formulation of the palmar arch, called the kinematic transverse
      arch that takes account of the thenar and hypothenar involvement in arch
      formation. Hand shape modulation during two natural power-grasping tasks was
      studied in eight healthy adults. Results showed a significant influence of the
      overall contribution of thenar and hypothenar movement during hand shape
      modulation. While there was relatively more thenar contribution during transport
      shaping, more hypothenar contribution was evident during preshaping and contact
      shaping-the two phases of grasping during which the hand establishes contact with
      the object. The advantage of the new formulation is that it better described the
      contributions from thenar and hypothenar movement to palmar arch formation which
      may be a more accurate depiction of hand preshaping during grasping.

PMID- 18076889
TI  - Excess isotherms as a new way for characterization of the columns for reversed
      phase liquid chromatography.
AB  - In this work, we present the excess isotherm of acetonitrile for stationary
      phases with different coverage density. Data obtained with the minor disturbance
      method were compared with (29)Si cross-polarization/magic-angle spinning NMR
      spectra to find dependence between acetonitrile adsorption on C18 chemically
      bonded stationary phases and coverage density of stationary phase. The
      preferential adsorption of acetonitrile on the bonded phase and the adsorption of
      water on the silica surface can be well correlated with the coverage density.

PMID- 18076890
TI  - Anserine and carnosine determination in meat samples by pure micellar liquid
      chromatography.
AB  - Anserine and carnosine, which are both imidazole dipeptides, are natural
      antioxidants that are present in some types of meat. A pure micellar liquid
      chromatographic procedure was developed using a micellar mobile phase of 0.10 M
      sodium dodecyl sulphate buffered at pH 7, an amino column and UV detection. Three
      types of stationary phases (C18, phenyl and amino columns) were examined and the
      procedure was used to determine the two compounds in meat samples. They were
      completely resolved without any interference from the protein band. Total
      analysis time was 12 min. The limits of detection (ng/mL) were 71 and 53 for
      anserine and carnosine, respectively. Calibration curves were constructed on
      three different days (r>0.998). Repeatability and intermediate precision were
      evaluated at three different concentrations in meat matrices, the residual
      standard deviations being below 2.1%. Meat samples of poultry, pork and beef were
      injected directly into the chromatographic system after extraction in a sodium
      dodecyl sulphate solution and filtration. The possibility of direct injection
      using micellar liquid chromatography reduces the cost and time of analyses, and
      decreases error sources owing to minimised risks of losses and chemical changes
      in the analytes. Moreover, the selection of a pure mobile phase of sodium dodecyl
      sulphate allows this procedure to offer a number of advantages, such as non
      toxicity, non-flammability, biodegradability and low cost, in comparison with
      aqueous-organic solvents. Its simplicity, then, makes it a good candidate for
      application in routine analysis in the area of food control and quality.

PMID- 18076891
TI  - Quantification of polychlorinated dibenzo-p-dioxins and dibenzofurans by direct
      injection of sample extract into the comprehensive multidimensional gas
      chromatograph/high-resolution time-of-flight mass spectrometer.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans in crude extracts of fly ash
      and flue gas from municipal waste incinerators were quantified using a
      comprehensive multidimensional gas chromatograph (GC x GC) coupled to a high
      resolution time-of-flight mass spectrometer (HR-TOFMS). For identification and
      quantification, we developed our own program to prepare 3D chromatograms of
      selected mass numbers from the data of the GC x GC/HR-TOFMS. Isolation of all
      congeners with a TCDD toxic equivalency factor from the other isomers by only one
      injection was confirmed. The instrumental detection limit of TCDD on the GC x
      GC/HR-TOFMS was 0.9 pg by the relative calibration method. Quantification of
      these substances in the crude extracts was achieved by direct injection to the GC
      x GC/HR-TOFMS. The results agree with the values obtained using a generic gas
      chromatography/high-resolution mass spectrometry (GC/HRMS) system. It was
      confirmed that measurement by high-resolution TOFMS and GC x GC effectively
      reduces interference from other chemicals.

PMID- 18076892
TI  - Analysis of basic compounds by reversed-phase high-performance liquid
      chromatography using hybrid inorganic/organic phases at high pH.
AB  - The retention and mass overload of five bases and a quaternary ammonium compound
      were studied on a bridged ethyl hybrid inorganic/organic phase (XBridge C18) over
      a pH range 2.7-12.0 using acetonitrile-phosphate and carbonate buffers. Some
      comparisons were drawn with results on a methyl hybrid (XTerra) phase. At low pH,
      rapid mass overload was observed with severe decreases in efficiency as sample
      mass was increased over the range 0.04-5 microg of solute. At intermediate pH
      (swpH 7.0), generally good peak shapes for small sample mass were still obtained
      on the ethyl hybrid, but with somewhat increased tailing of bases compared with
      swpH 2.7. At higher pH (swpH 10), good peak shape and improved loadability were
      obtained for moderately strong bases, due to their occurrence mostly as neutral
      species. However, stronger bases gave poor efficiency, attributed to interaction
      of the charged basic solute with increasingly ionised column silanol groups.
      Results were broadly similar on the methyl hybrid at swpH 10. At swpH 11, unusual
      profiles of increasing followed by decreasing efficiency were obtained on the
      ethyl hybrid for some bases as sample mass was increased; improved results were
      obtained at swpH 12. While the column loadability increased substantially at the
      highest pH studied, tailing for small sample mass was still more severe than at
      low pH, even though all compounds were <1% ionised in the mobile phase.

PMID- 18076893
TI  - Toward chromatographic analysis of interacting protein networks.
AB  - Protein complexes, collectively referred to as the cellular interactome, appear
      to play a major role in cellular regulation. At present it is thought that the
      interactome could be composed of hundreds of protein assemblies. The objective of
      the work described here was to examine the prospect that chromatographic methods
      widely used in the preparative isolation of native proteins could be incorporated
      into global proteomics methods in such a way that the primary structure of
      protein complexes of sufficient stability to survive chromatography could be
      recognized along with their participation in protein complexes. Because wide
      differences in sizes are a unique feature of protein complexes, size-exclusion
      chromatography (SEC) was incorporated into all the fractionation strategies
      examined. Anion-exchange chromatography (AEC) and hydrophobic-interaction
      chromatography (HIC) were also examined because of the broad utility that these
      methods have shown in the preparation of proteins with native structure. Slightly
      more than a third of all proteins identified in yeast lysates were found to elute
      from SEC, AEC, and HIC columns with an apparent molecular weight much higher than
      that predicted from their parent gene. These results were interpreted to mean
      that these proteins were migrating through columns as components of protein
      complexes. Based on studies with multidimensional SEC-->RPLC (reversed-phase
      liquid chromatography), AEC-->SEC, and HIC-->SEC systems, it was concluded that
      recognition of proteins in complexes could be easily incorporated into
      multidimensional chromatographic methods for global proteomics when at least one
      of the fractionation dimensions included SEC of native proteins.

PMID- 18076894
TI  - Uptake of amitriptyline and nortriptyline with liposomes, proteins, and serum:
      implications for drug detoxification.
AB  - Liposomes composed of DOPG and DMPC were studied for their ability to sequester
      amitriptyline and nortriptyline under physiological conditions. The liposomes
      reduced the free drug concentration in protein mixtures and in human serum, but
      the drug uptake efficiency of liposomes was reduced in the presence of plasma
      proteins, perhaps due to adsorption of proteins on the liposomes. The reduction
      was significantly more for the pure DOPG liposomes. The 50:50 DMPC:DOPG liposomes
      (0.72 mg lipid/mL) reduced the free amitriptyline concentration by 50-60% in the
      presence of 7% proteins (4% albumin (w/w), 2% fibrinogen (w/w), 1% globulins
      (w/w)). In human serum, the free drug reduction was 35-70% with the same 50:50
      liposomes (0.72 mg lipid/mL). The liposomal systems were equally efficient at
      sequestering nortriptyline, which is a major metabolite of amitriptyline. The
      drug binding to liposomes in the presence of serum proteins is also quick and
      reversible and the likely mechanism of drug sequestration is adsorption of drug
      on the surface of liposomes. Accordingly, the drug uptake increases with
      increased charge and lipid loading. Even though the serum proteins reduced the
      effectiveness of the liposomes at sequestering the drug, the 50:50 DMPC:DOPG
      liposomes may be effective at treating amitriptyline overdose patients.

PMID- 18076895
TI  - An AFM, XPS and wettability study of the surface heterogeneity of PS/PMMA-r-PMAA
      demixed thin films.
AB  - A series of homopolymer/random copolymer blends was used to produce heterogeneous
      surfaces by demixing in thin films. The chosen homopolymer is polystyrene (PS)
      and the random copolymer is poly(methyl methacrylate)-r-poly(methacrylic acid)
      (PMMA-r-PMAA), whose acidic functions could be used as reactive sites in view of
      further surface functionalization. The proportion of each polymer at the
      interface was deduced from X-ray photoelectron spectroscopy (XPS) data using, on
      the one hand, the O/C ratio, and on the other hand, decomposition of the carbon
      peak of the blends in two components corresponding to the carbon peaks of PS and
      PMMA-r-PMAA. Combining the information from XPS with atomic force microscopy
      (AFM) images, water contact angle measurements and PS selective dissolution, it
      appears that the surfaces obtained from blends with a high PS content (90/10 to
      70/30) display pits with a bottom made of PMMA-r-PMAA, randomly distributed in a
      PS matrix. On the other hand, the surfaces obtained from blends with a low PS
      content (30/70 to 10/90) display randomly distributed PS islands surrounded by a
      PMMA-r-PMAA matrix. The characteristics of the heterogeneous films are thought to
      be governed by the higher affinity of PMMA-r-PMAA for the solvent (dioxane),
      which leads to the elevation of the PS phase compared to the PMMA-r-PMAA phase,
      and to surface enrichment in PMMA-r-PMAA.

PMID- 18076896
TI  - The dependence of hematite site-occupancy standard state triple-layer model
      parameters on inner-layer capacitance.
AB  - Potentiometric acid-base titration data for three hematite samples that differed
      on the basis of specific surface area (17.4, 33, 83 m2/g for hematite A, B, and
      C, respectively) was analyzed using the triple-layer model (TLM). The sensitivity
      of the TLM fits of the data to the choice of site density (N(s)) was evaluated
      from 1.5 to 22 sites/nm2. In general, little dependence in the quality of fit was
      determined, irrespective of the value of Ns. Values of the electrolyte adsorption
      equilibrium constants (log K cation 0 and log K anion 0) steadily increased with
      decreasing Ns. These constants are consistent with the commonly used 1.0 M
      standard state and when converted into comparable constants consistent with the
      site-occupancy standard state (log K cation theta and log K anion theta) a single
      value for each respective constant was determined. Values of the inner-layer
      capacitance (C1) were varied during these optimizations and increased with
      decreasing Ns, particularly below 5 sites/nm2. The optimized C1 values exhibited
      an apparent inverse relationship with specific surface area (i.e., C1 for
      hematite A>C1 for hematite B>C1 for hematite C). The magnitude of change in C1
      with respect to Ns depended upon the magnitude of C1 for each hematite as the
      higher the C1 value, the greater was the change with respect to Ns. These results
      suggest when the site-occupancy standard state parameters are used to predict
      constants at different site density values without re-regression of titration
      data that variations in C1 should be accounted for, particularly for low specific
      surface area samples that have a high C1.

PMID- 18076897
TI  - Viscoelastic properties of polystyrene and poly(methyl methacrylate) dispersions
      sterically stabilized by hydrophobically modified inulin (polyfructose) polymeric
      surfactant.
AB  - Recently, steric repulsive forces induced by a new graft copolymer surfactant,
      which is based in inulin (polyfructose), have been described. Previous
      investigations by atomic force microscopy between solid surfaces covered with
      adsorbed surfactant indicated strong repulsive forces even at high electrolyte
      concentration, due to the steric repulsion produced by the surfactant hydration.
      In the present paper, the colloidal stabilization provided by this surfactant is
      studied by rheology. The measurements were carried out on sterically stabilized
      polystyrene (PS) and poly(methyl methacrylate) (PMMA) containing adsorbed
      surfactant (INUTEC SP1). Steady-state shear stress as a function of shear rate
      curves was established at various latex volume fractions. The viscosity volume
      fraction curves were compared with those calculated using the Doughtry-Krieger
      equation for hard sphere dispersions. From the experimental eta r-phi curves the
      effective volume fraction of the latex dispersions could be calculated and this
      was used to determine the adsorbed layer thickness Delta. The value obtained was
      9.6 nm, which is in good agreement with that obtained using atomic force
      microscopy (AFM). Viscoelastic measurements of the various latex dispersions were
      carried out as a function of applied stress (to obtain the linear viscoelastic
      region) and frequency. The results showed a change from predominantly viscous to
      predominantly elastic response at a critical volume fraction (phi c). The
      effective critical volume fraction, phi eff, was calculated using the adsorbed
      layer thickness (Delta) obtained from steady-state measurements. For PS latex
      dispersions phi eff was found to be equal to 0.24 whereas for PMMA phi eff=0.12.
      These results indicated a much softer interaction between the latex dispersions
      containing hydrated polyfructose loops and tails when compared with latices
      containing poly(ethylene oxide) (PEO) layers. The difference could be attributed
      to the stronger hydration of the polyfructose loops and tails when compared with
      PEO. This clearly shows the much stronger steric interaction between particles
      stabilized using hydrophobically modified inulin.

PMID- 18076898
TI  - Ga2O3 and GaN nanocrystalline film: reverse micelle assisted solvothermal
      synthesis and characterization.
AB  - Gallium oxide (beta-Ga2O3) nanoparticles were successfully deposited on quartz
      glass substrates using sodium bis(2-ethylhexyl) sulfosuccinate (AOT)/n
      hexane/ethylene glycol monomethyl ether (EGME) reverse micelle-mediated
      solvothermal process with different omega values. The mean diameter of Ga2O3
      particles was approximately 2-3 nm and found to be approximately independent of
      omega values of the reverse micelles. However, when the Ga2O3 nanocrystalline
      films were nitrided at 900 degrees C under flowing NH3 atmosphere for 1 h, the
      mean diameter of the resulted gallium nitride (wurtzite-GaN) nanoparticles varied
      from 3-9 nm. Both nanocrystalline films of Ga2O3 and GaN were characterized by X
      ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform
      infrared (FTIR) spectroscopy, UV-vis spectroscopy and photoluminescence in order
      to study their chemical and physical properties explicitly.

PMID- 18076899
TI  - Salt-induced viscoelastic wormlike micelles formed in surface active ionic liquid
      aqueous solution.
AB  - The growth and structure of the aqueous micellar solutions of a surface active
      ionic liquid, 1-hexadecyl-3-methylimidazolium bromide (C16mimBr), in the presence
      of an organic salt sodium tosylate (NaTos), were investigated by rheological
      measurements and freeze-fracture transmission electron microscopy at room
      temperature (298 K). As in some conventional ionic surfactant/salt aqueous
      systems, wormlike micelles and network structures could be formed in the
      C16mimBr/NaTos aqueous solutions, according to measurements of the zero-shear
      viscosity, the entanglement length, the average contour length, as well as
      application of the Cox-Merz empirical rule and Cole-Cole plots. FF-TEM images
      further confirmed that wormlike micelles were formed in these aqueous solutions.
      The wormlike micelles presented here would expand potential applications of ionic
      liquids in home care products, oilfield stimulation fluids, and
      nanobiotechnology.

PMID- 18076900
TI  - Molecular detection of betanodaviruses from apparently healthy wild marine
      invertebrates.
AB  - One hundred eighteen samples (21 species) of wild marine invertebrates were
      collected from western and southern coastal area of Korean Peninsula. Four of 78
      (18 species) samples collected at Namhae (South) area were positive for nodavirus
      in nested PCR test. Of the 40 samples (5 species) collected at Hwanghae (West)
      areas, all samples were negative for nodavirus in both RT-PCR and nested PCR
      tests. Positive nested PCR results were obtained from the following species:
      Charybdis bimaculata Charybdid crab; Pandalus hypsinotus Southern humpback shrimp
      and Mytilus galloprovincialis Mediterranean mussel. Phylogenetic analysis based
      on the partial nucleotide sequence (177 bases) of the RNA2 coat protein gene
      showed that the four strains were highly homologous (100%) and closely related to
      that of the known betanodaviruses, redspotted grouper nervous necrosis virus
      (RGNNV). These results indicate that nodavirus is present from wild marine
      invertebrates in the southern coastal areas of Korean Peninsula. These
      subclinically infected marine invertebrates may constitute an inoculum source for
      betanodavirus infection and cause mortality in cultured fishes in Korea.

PMID- 18076901
TI  - Overexpression of glutaredoxin-2 reduces myocardial cell death by preventing both
      apoptosis and necrosis.
AB  - Mitochondrial glutaredoxin-2 (Glrx2) has been recognized as an important redox
      regulator in mammalian organs including heart. To date no investigations have
      addressed the potential role of Glrx2 in cardiac disorders. The present study
      examined if myocardial overexpression of Glrx2 in the heart could rescue the
      cardiac cells from apoptosis and necrosis induced by ischemia and reperfusion.
      The human Glrx2 transgene was created by placing a full-length cDNA fragment
      encoding human mitochondrial Glrx2 downstream to the 5' flanking sequence and
      promoter of the mouse alpha-myosin heavy chain gene. The isolated hearts from
      Glrx2 transgenic mice and non-transgenic (wild type) littermates [on c57BL/6xC3H
      hybrid background] were subjected to 30 min of global ischemia followed by 2 h of
      reperfusion via working mode. The hearts from Glrx2 transgenic mice displayed
      significantly improved contractile performance and reduced myocardial infarct
      size and cardiomyocyte apoptosis. There was a reduction in cytochrome c release
      and activation of caspase 3 and caspase 9. Glrx2 overexpression also reduced the
      ischemia/reperfusion-mediated loss of mitochondrial cardiolipin, decreased the
      activities of reactive oxygen species (ROS) and preserved GSH/GSSG ratio. Glrx2
      mediated survival signal appeared to be stemmed from PI-3-kinase-Akt survival
      signaling pathway and involved the activation of redox sensitive transcription
      factor NFkappaB and antiapoptotic protein Bcl-2. The results indicated a crucial
      role of mitochondrial Glrx2 in cardioprotection.

PMID- 18076902
TI  - A nested gene in Streptomyces bacteria encodes a protein involved in quaternary
      complex formation.
AB  - The gene pgaM is involved in the biosynthesis of an angucycline-type polyketide
      antibiotic in Streptomyces sp. PGA64. It encodes a two-domain polypeptide
      consisting of an N-terminal flavoprotein oxygenase and a C-terminal short-chain
      alcohol dehydrogenase/reductase, which are fused together at the translational
      level as a result of end codon deletion. Here we show that translation also
      initiates at an internal start codon that enables independent expression of a
      separate reductase subunit, PgaMred. This confirms that the gene exhibits a rare
      viral-like arrangement of two overlapping reading frames that allows simultaneous
      expression of two alternative forms of the protein. Together, these two proteins
      associate to form a stable non-covalent complex, the native form of PgaM. The
      reductase subunit PgaMred is shown to provide enzyme stability and to affect the
      redox state of the oxygenase domain FAD. Finally, a model for the quaternary
      structure of the complex that explains the necessity for a nested gene system and
      the unusual behaviour of the protein subunits in vitro is presented.

PMID- 18076903
TI  - The neuralized homology repeat 1 domain of Drosophila neuralized mediates nuclear
      envelope association and delta-dependent inhibition of nuclear import.
AB  - Signaling by the Notch (N) pathway is critical for many developmental processes
      and requires complex trafficking of both the N receptor and its transmembrane
      ligands, Delta (Dl) and Serrate. neuralized encodes an E3 ubiquitin ligase
      required for N ligand internalization. Neuralized (Neur) is conserved from worms
      to humans and comprises two Neur homology repeat (NHR) domains, NHR1 and NHR2,
      and a carboxyl-terminal RING domain. We have previously shown that the RING
      domain is required for ubiquitin ligase activity and that NHR1 mediates binding
      to Dl, a ubiquitination target. In Drosophila, Neur associates with the plasma
      membrane and hepatocyte responsive serum phosphoprotein-positive endosomes. Here
      we demonstrate that Neur also exhibits nuclear envelope localization. We have
      determined that Neur subcellular localization is regulated by nuclear trafficking
      and that inhibition of chromosome region maintenance 1, a nuclear export
      receptor, interferes with Neur nuclear export, trapping Neur in the nucleus.
      Moreover, we demonstrate that nuclear envelope localization is mediated by the
      Neur NHR1 domain. Interestingly, Dl expression in Schneider cells is sufficient
      to inhibit Neur nuclear import and inhibition occurs in an NHR1-dependent manner,
      suggesting that Neur nuclear localization occurs in contexts where Dl expression
      is either low or absent. Consistent with this, we found that Neur exhibits
      nuclear trafficking and associates with the nuclear envelope in the secretory
      cells of the larval salivary gland and that overexpression of Dl can reduce Neur
      localization to the nucleus. Altogether, our data demonstrate that Neur localizes
      to the nuclear envelope and that this localization can be negatively regulated by
      Dl, suggesting a possible nuclear function for Neur in Drosophila.

PMID- 18076904
TI  - Crystal structure of a complex between the phosphorelay protein YPD1 and the
      response regulator domain of SLN1 bound to a phosphoryl analog.
AB  - The crystal structure of the yeast SLN1 response regulator (RR) domain bound to
      both a phosphoryl analog [beryllium fluoride (BeF(3)(-))] and Mg(2+), in complex
      with its downstream phosphorelay signaling partner YPD1, has been determined at a
      resolution of 1.70 A. Comparisons between the BeF(3)(-)-activated complex and the
      unliganded (or apo) complex determined previously reveal modest but important
      differences. The SLN1-R1 x Mg(2+) x BeF(3)(-) structure from the complex provides
      evidence for the first time that the mechanism of phosphorylation-induced
      activation is highly conserved between bacterial RR domains and this example from
      a eukaryotic organism. Residues in and around the active site undergo slight
      rearrangements in order to form bonds with the essential divalent cation and
      fluorine atoms of BeF(3)(-). Two conserved switch-like residues (Thr1173 and
      Phe1192) occupy distinctly different positions in the apo versus BeF(3)(-)-bound
      structures, consistent with the "Y-T" coupling mechanism proposed for the
      activation of CheY and other bacterial RRs. Several loop regions and the alpha 4
      beta 5-alpha 5 surface of the SLN1-R1 domain undergo subtle conformational
      changes ( approximately 1-3 A displacements relative to the apo structure) that
      lead to significant changes in terms of contacts that are formed with YPD1.
      Detailed structural comparisons of protein-protein interactions in the apo and
      BeF(3)(-)-bound complexes suggest at least a two-state equilibrium model for the
      formation of a transient encounter complex, in which phosphorylation of the RR
      promotes the formation of a phosphotransfer-competent complex. In the BeF(3)(-)
      activated complex, the position of His64 from YPD1 needs to be within ideal
      distance of and in near-linear geometry with Asp1144 from the SLN1-R1 domain for
      phosphotransfer to occur. The ground-state structure presented here suggests that
      phosphoryl transfer will likely proceed through an associative mechanism
      involving the formation of a pentacoordinate phosphorus intermediate.

PMID- 18076905
TI  - Prospective associations between cannabis use, abuse, and dependence and panic
      attacks and disorder.
AB  - The present study prospectively evaluated cannabis use, abuse, and dependence in
      relation to the development of panic attacks and panic disorder. Participants at
      the start of the study were adolescents (n=1709) with a mean age of 16.6 years
      (SD=1.2; time 1) and were re-assessed 1 year later (time 2) and then again as
      young adults (time 3; mean age=24.2 years, SD=0.6). Results indicated that
      cannabis use and dependence were significantly prospectively associated with an
      increased odds for the development of panic attacks and panic disorder. However,
      cannabis was not incrementally associated with the development of panic after
      controlling for daily cigarette smoking. The theoretical and clinical
      implications of these findings are discussed.

PMID- 18076906
TI  - Relationship of general medical burden, duration of illness and age in patients
      with bipolar I disorder.
AB  - OBJECTIVE: This study was aimed at evaluating general medical burden in a group
      of 111 patients with bipolar I disorder. METHODS: Data were drawn from
      participants entering the Bipolar Disorder Center for Pennsylvanians (BDCP)
      protocol. General medical burden was assessed by completing the Cumulative
      Illness Rating Score (CIRS) from chart review. RESULTS: The mean age of the
      sample was 42.1 (11.5), mean CIRS total score was 4.7 (2.9), and mean number of
      categories endorsed was 3.4 (1.7). Medical burden showed a positive relationship
      with increasing age and with duration of illness. CIRS scores and number of
      organ/system categories endorsed were significantly higher in patients with more
      than 21 years of illness than in patients with 0-9 years of illness (p<.0001) or
      with 10-20 years of illness (p<.0001). Medical burden was related to duration of
      illness even after controlling for age. The most frequently endorsed illness
      categories were cardiovascular disease, (with hypertension and hyperlipidemia
      being the most frequent conditions) and endocrine/metabolic (with obesity,
      thyroid dysfunction, and type 2 diabetes being the most common conditions).
      CONCLUSIONS: Patients with bipolar disorder carry a substantial burden of general
      medical conditions, related to age and duration of illness. These results suggest
      that the development and testing of specific interventions that target medical
      risk factors and medical burden in patients with bipolar disorder are urgently
      needed, especially early in the course of the illness, when patients appear to
      accumulate medical comorbidity at a rapid rate.

PMID- 18076907
TI  - Countable and non-countable microembolic signals by TCD in first-ever stroke or
      TIA patients with PFO.
AB  - BACKGROUND: There are data in the literature indicating that the number of
      microembolic signals (MES) in patients with patent foramen ovale (PFO) is
      directly related to stroke incidence and recurrence. We thus hypothesized that
      the amount of artificially induced microembolic signals monitored by contrast
      transcranial Doppler (cTCD) would be greater in younger patients with PFO and
      stroke (when cryptogenic strokes related to the PFO are frequent). PATIENTS AND
      METHODS: The final analysis included 109 patients with first-ever ischemic stroke
      or TIA with PFO, as detected by Transesophageal Echocardiography (TEE), and MES,
      as measured by cTCD. Thirty-seven patients (aged 19-45 years) were defined as the
      "younger" group, and the other 72 patients (aged 46-77 years) were defined as the
      "older" group. Eighty-six patients (78.9%) suffered from stroke, including 28 in
      the younger group and 58 in the older group. The pattern of microembolization was
      defined as "countable" when the observers were able to calculate the number of
      MES. In the case of a "shower" of MES on TCD examination, the pattern of
      monitoring was defined as "non-countable." RESULTS: Ischemic heart disease, and
      hyperlipidemia were found to be significantly more frequent in the group of older
      patients. Twenty-three patients (62.2%) in the younger group had cryptogenic
      stroke or TIA (no risk factors found), as compared to 26 patients (36.1%) in the
      older group (p=0.009). There were 23 patients with a non-countable pattern of MES
      in the older group, as compared with 5 such patients in the younger group
      (p=0.04). There was no difference found in the number of MES between the groups
      in those patients with a countable pattern of MES (13.3+/-11.8 in the younger
      group vs. 13.7+/-11.7 in the older group). CONCLUSIONS: In stroke and TIA
      patients above 45 years of age, PFOs producing a large amount of MES on TCD
      examination are frequent. Thus, there is no correlation between a large amount of
      MES and stroke or TIA in young patients.

PMID- 18076908
TI  - Understanding stem cell differentiation through self-organization theory.
AB  - The mechanism underling stem cells' key property, the ability to either divide
      into two replicate cells or a replicate and a differentiated daughter, still is
      not understood. We tested a hypothesis that stem cell asymmetric
      division/differentiation is spontaneously created by the coupling of processes
      within each daughter and the resulting biochemical feedbacks via the exchange of
      molecules between them during mitotic division. We developed a
      mathematical/biochemical model that accounts for dynamic processes accompanying
      division, including signaling initiation and transcriptional, translational and
      post-translational (TTP) reactions. Analysis of this model shows that it could
      explain how stem cells make the decision to divide symmetrically or
      asymmetrically under different microenvironmental conditions. The analysis also
      reveals that a stem cell can be induced externally to transition to an
      alternative state that does not have the potentiality to have the option to
      divide symmetrically or asymmetrically. With this model, we initiated a search of
      large databases of transcriptional regulatory network (TRN), protein-protein
      interaction, and cell signaling pathways. We found 12 subnetworks (motifs) that
      could support human stem cell asymmetric division. A prime example of the
      discoveries made possible by this tool, two groups of the genes in the genetic
      model are revealed to be strongly over-represented in a database of cancer
      related genes.

PMID- 18076909
TI  - Investigation of cellular movement in the prostate epithelium using an agent
      based model.
AB  - Experimental patterns of epithelial cell proliferation in the prostate suggest
      that cell movement may play an important role in prostate epithelial homeostasis,
      and genes known to regulate cell movement are commonly mutated or deleted in
      prostate carcinomas. However, the nature of cell movement within the prostate
      epithelium remains unknown. Here, the role of cellular movement in the prostate
      epithelium was explored by developing an agent-based model of the prostate duct.
      Prostatic adult stem cells, transit amplifying/intermediate cells (TA/ICs), and
      luminal cells were individually modeled within a three-dimensional reconstruction
      of a prostate duct. Different movement behaviors for TA/ICs and luminal cells
      were assessed by their ability to recreate experimental patterns of prostate cell
      proliferation and epithelial morphology. Strongly directed TA/IC movement toward
      the distal region of the prostate duct combined with weakly directed luminal cell
      movement toward the proximal region of the prostate duct was able to best
      recreate experimental patterns of prostate proliferation and morphology. The
      effects on cell mobility from abnormalities in PTEN and thymosin beta15
      (Tbeta15), genes which are commonly altered in prostate cancer, were simulated in
      the model. These simulations show that altering prostate stem cell movement can
      dysregulate epithelial homeostasis and lead to excessive cell growth, suggesting
      that disruption of cell movement may contribute to prostate carcinogenesis.

PMID- 18076910
TI  - Simple criteria for finding (nearly) optimal vaccination strategies.
AB  - Strategies for best controlling the spread of the diseases with limited vaccine
      available are explored. I use influenza as a representative disease in point. The
      model describes the dynamics of influenza spread among multiple groups that have
      different risks and activity levels. I define a core group consisting of
      individuals with occupations that brings them in contact with many other people
      in a day. These occupations may include service industries, teachers, health
      care, and government workers, to name a few. High-risk individuals are those as
      typically designated for: children under 5 and adults over 50, people with
      weakened immune systems as well as emergency and health care personnel. Under
      certain conditions, shifting vaccination resources away from the high-risk group
      to the high-activity group will result in improved herd immunity in both the high
      risk group and the population as whole. This results in more high-risk people
      protected even though less of them are being vaccinated, with the obvious
      implications that current vaccination policies may be far less then optimal. I
      show that the criteria for the optimal strategy can be derived from simple
      expressions gleaned from the expression for the basic reproductive number.

PMID- 18076912
TI  - The usefulness of the detection of GSTP1 methylation in urine as a biomarker in
      the diagnosis of prostate cancer.
AB  - PURPOSE: Prostate cancer has a unique set of problems associated with its early
      detection and diagnosis that might be aided by the addition of molecular markers,
      such as DNA hypermethylation. DNA methylation is an important epigenetic
      mechanism of gene regulation that has a critical role in normal developmental
      processes. Aberrant DNA methylation is a hallmark of carcinogenesis and GSTP1
      hypermethylation is the most common molecular alteration in human prostate
      cancer. To our knowledge the clinical usefulness of the detection of gene
      methylation is yet to be established. MATERIALS AND METHODS: We evaluated GSTP1
      hypermethylation in urine collected after prostatic massage and in core needle
      biopsies from 100 men referred for diagnostic biopsy. RESULTS: Methylation of
      GSTP1 in urine specimens had 75% sensitivity and 98% specificity for prostate
      cancer. GSTP1 methylation in the biopsy had 88% specificity and 91% sensitivity.
      Interestingly we observed a higher frequency of GSTP1 methylation in the urine of
      men with stage III vs II disease (100% vs 20%, p = 0.05). CONCLUSIONS: This study
      suggests that the detection of GSTP1 methylation in prediagnostic urine may
      improve the specificity of PSA and help distinguish men with prostate cancer from
      those with benign prostatic hyperplasia. This finding should be further explored
      in a larger, prospective screening trial.

PMID- 18076911
TI  - Repeated games and direct reciprocity under active linking.
AB  - Direct reciprocity relies on repeated encounters between the same two
      individuals. Here we examine the evolution of cooperation under direct
      reciprocity in dynamically structured populations. Individuals occupy the
      vertices of a graph, undergoing repeated interactions with their partners via the
      edges of the graph. Unlike the traditional approach to evolutionary game theory,
      where individuals meet at random and have no control over the frequency or
      duration of interactions, we consider a model in which individuals differ in the
      rate at which they seek new interactions. Moreover, once a link between two
      individuals has formed, the productivity of this link is evaluated. Links can be
      broken off at different rates. Whenever the active dynamics of links is
      sufficiently fast, population structure leads to a simple transformation of the
      payoff matrix, effectively changing the game under consideration, and hence
      paving the way for reciprocators to dominate defectors. We derive analytical
      conditions for evolutionary stability.

PMID- 18076913
TI  - Reprogramming requirements after sacral nerve stimulator implantation:
      correlation with preoperative indication.
AB  - PURPOSE: Recent publications support sacral nerve stimulator implantation in
      patients with interstitial cystitis. To our knowledge the reprogramming
      requirements for all patients following stimulator implantation has not been
      described and it is unknown whether the number of sessions required vary by pre
      implantation diagnosis. We determined overall reprogramming requirements
      following nerve stimulator implantation and whether requirements vary based on
      preoperative indication. MATERIALS AND METHODS: After obtaining institutional
      review board approval we retrospectively reviewed the records of all patients who
      underwent sacral nerve stimulator implantation at our institution between June
      2002 and October 2004. The preoperative indication and number of reprogramming
      sessions during the initial test period (stage 1) and following permanent
      implantation (stage 2) were compared. RESULTS: The 17 patients proceeding to
      stage 2 with a minimum 12-month followup during the study period were included.
      Mean age was 43 years (range 26 to 78) and all patients except 1 were female.
      Patients were separated by diagnosis for evaluation purposes, including
      urgency/frequency/incontinence in 8, urinary retention in 2 and interstitial
      cystitis in 7. The average number of reprogramming sessions during stage 1 was
      0.9, 3.5 and 2.3 for urgency/frequency/incontinence, urinary retention and
      interstitial cystitis, respectively. The average number of reprogramming sessions
      after stage 2 was 2.8, 3.0 and 6.9 at 12-month followup for
      urgency/frequency/incontinence, urinary retention and interstitial cystitis,
      respectively. No patient had the stimulator removed for reprogramming failure.
      CONCLUSIONS: Patients in urinary retention appear to require more frequent
      reprogramming during stage 1, while patients with interstitial cystitis require
      more sessions after stage 2 implantation.

PMID- 18076915
TI  - Laparoscopic renal oncological surgery in the presence of abdominal aortic and
      vena caval pathology: 8-year experience.
AB  - PURPOSE: To our knowledge the outcomes of laparoscopic renal oncological surgery
      in patients with major aortic and/or inferior vena caval pathology are unknown.
      We present our experience spanning an 8-year period. MATERIALS AND METHODS: From
      March 1998 to October 2006, 1,826 laparoscopic renal procedures were performed
      for tumor. Of these patients 66 (3.6%) had major abdominal aortic or vena caval
      pathology concomitantly. Demographics, specific entities of the vascular disease,
      and intraoperative and postoperative data were reviewed. RESULTS: A total of 66
      patients had a history of abdominal aortic disease (54), vena caval disease (9)
      or both (3). Of the patients 85% had 3 or greater comorbidities, 88% had an
      American Society of Anesthesiologists score of 3 or greater and 88% were on
      chronic anticoagulation therapy. A total of 27 patients (41%) had undergone prior
      surgical treatment for vascular pathology. Laparoscopic renal surgery, which was
      transperitoneal in 25 cases and retroperitoneal in 41, included radical
      nephrectomy in 20, partial nephrectomy in 17 and cryoablation in 29. Open
      conversion was performed in 3 patients (5%). There were 3 intraoperative (5%) and
      9 postoperative (14%) complications. One patient died of pulmonary sepsis. There
      was no statistically significant difference in perioperative outcomes between the
      aortic and vena caval disease groups. The retroperitoneal approach was associated
      with less blood loss and shorter operative time (p = 0.0003 and 0.004,
      respectively). CONCLUSIONS: Laparoscopic surgery for renal tumor in the presence
      of aortic or vena caval disease is safe and feasible. Considerable prior
      laparoscopic experience is necessary when treating these patients at high risk.

PMID- 18076916
TI  - Prostate volume estimation using the ellipsoid formula consistently
      underestimates actual gland size.
AB  - PURPOSE: Historically estimating prostate volume by transrectal ultrasound
      underestimates actual prostate weight. We quantified and determined whether
      trends could be identified to predict or understand the underestimation.
      MATERIALS AND METHODS: The characteristics transrectal ultrasound volume,
      pathological prostate weight and dimensions in 181 patients were entered into an
      electronic spread sheet. Pathological and transrectal ultrasound volume was
      estimated using the standard ellipsoid formula, width x height x length x pi/6.
      In 87 of the 181 cases transrectal ultrasound dimensions were compared to
      pathological dimensions. RESULTS: Using pathologically determined dimensions the
      ellipsoid formula accurately (+/-10%) predicted weight in 26.5% of the cases vs
      13.3% by ultrasound. Transrectal ultrasound underestimated it by greater than 30%
      in 55% of cases and overestimated (greater than 10%) it in only 6.4%. Small vs
      large gland weight did not predict less underestimation. For prostate weight less
      than 30, 30 to 60 and more than 60 gm transrectal ultrasound underestimated by
      greater than 20% in 22.2%, 24.7% and 25.7% of cases, respectively. Paired
      analysis of transrectal ultrasound measurements and pathological dimensions
      revealed that transrectal ultrasound length was accurate (4.4 vs 4.3 cm) and had
      a good correlation with prostate weight. Height was underestimated (3.2 vs 3.7
      cm) but it correlated with weight. Width was inaccurate (4.8 vs 5.2 cm) and it
      correlated poorly with weight. Age, prostate specific antigen, stage, Gleason
      score, American Urological Association symptom score and body mass index were not
      predictive of the underestimation. Displaced water volume in cc per prostate
      weight in gm showed a correlation of 0.997. CONCLUSIONS: The primary underlying
      factor for inconsistency with volume estimation of prostate weight appears to be
      the ellipsoid formula since pathologically determined dimensions still had a 75%
      error. Independent of gland size the transrectal ultrasound correlation
      underestimated weight 80% of the time by greater than 30% in 55% of patients.
      Contrary to previous reports, transrectal ultrasound width and not length is the
      least reliable factor.

PMID- 18076917
TI  - Florida bladder cancer trends 1981 to 2004: minimal progress in decreasing
      advanced disease.
AB  - PURPOSE: There are no accepted screening recommendations for bladder cancer,
      although the greatest risk factors for bladder cancer are identifiable and
      modifiable, ie tobacco exposure. Bladder cancer survival correlates highly with
      disease stage. We ascertained whether there have been any demographic changes in
      the stage at presentation and mortality of bladder cancer in Florida during the
      last 25 years. MATERIALS AND METHODS: Data from Florida Cancer Data Registry were
      evaluated on all bladder cancer cases between 1981 and 2004. Cases were coded and
      analyzed as local, in situ or advanced (regional and distant) disease. Cases were
      stratified by demographic groups. RESULTS: The overall incidence of bladder
      cancer decreased slightly in the last 25 years from 24.3 to 20.5 cases per
      100,000 population. Overall white and Hispanic males had an almost 3 and 2-fold
      incidence of bladder cancer, respectively, compared to that in black males. White
      females had an almost 2-fold increased incidence compared to black and Hispanic
      females. Advanced stage bladder cancer decreased minimally in the 25 years. White
      and black females had the smallest decrease in the annual percent change of
      advanced bladder cancer. There was only a minimal decrease in bladder cancer
      mortality rates in black and white but not Hispanic individuals. CONCLUSIONS:
      Despite knowledge of the main risk factors for bladder cancer there were only
      small decreases in the percent of patients presenting with advanced disease in
      Florida in the last 25 years. Thus, bladder cancer may be an appropriate cancer
      for increased public awareness campaigns and potentially targeted screening of
      high risk populations.

PMID- 18076918
TI  - Prevention of recurrence with epirubicin and lactobacillus casei after
      transurethral resection of bladder cancer.
AB  - PURPOSE: A prospective, randomized, controlled trial was done to evaluate whether
      oral administration of a preparation of the probiotic agent Lactobacillus casei
      (Yakult Honsha, Tokyo, Japan) could enhance the prevention of recurrence by
      intravesical instillation of epirubicin after transurethral resection for
      superficial bladder cancer. MATERIALS AND METHODS: Between August 1999 and
      December 2002, 207 patients clinically diagnosed with superficial bladder cancer
      were included as study candidates and underwent transurethral resection, followed
      by intravesical instillation of 30 mg epirubicin/30 ml saline twice during 1
      week. After histological confirmation of superficial bladder cancer they were
      again included as study participants with 102 randomized to receive treatment
      with 6 additional intravesical instillations of epirubicin during the 3-month
      period after transurethral resection (epirubicin group) and 100 randomized to
      intravesical chemotherapy on the same schedule as the epirubicin group plus oral
      administration of 3 gm Lactobacillus casei preparation per day for 1 year
      (epirubicin plus Lactobacillus casei group). Patients were evaluated for
      intravesical recurrence, disease progression, prognosis and adverse drug
      reactions. RESULTS: The 3-year recurrence-free survival rate was significantly
      higher in the epirubicin plus Lactobacillus casei group than in the epirubicin
      group (74.6% vs 59.9%, p = 0.0234), although neither progression-free nor overall
      survival differed between the groups. The incidence of adverse drug reactions did
      not significantly differ between the groups and there were no serious adverse
      drug reactions. CONCLUSIONS: Intravesical instillation of epirubicin plus oral
      administration of Lactobacillus casei preparation is a novel, promising treatment
      for preventing recurrence after transurethral resection for superficial bladder
      cancer.

PMID- 18076920
TI  - Differences in organ system of distant metastasis by renal cell carcinoma
      subtype.
AB  - PURPOSE: The majority of the published data regarding the rates of renal cell
      carcinoma metastasis to specific locations has examined renal cell carcinoma as a
      whole. We evaluated site of distant metastasis by renal cell carcinoma
      histological subtype. MATERIALS AND METHODS: We studied 910 patients treated with
      radical nephrectomy for clear cell, papillary or chromophobe renal cell carcinoma
      at the Mayo Clinic between 1970 and 2000 who had distant metastasis at
      nephrectomy or who had metastasis during followup. The sites of metastases were
      compared by histological subtype using the chi-square and Fisher exact tests.
      RESULTS: There were 853 (94%) patients with clear cell, 39 (4%) with papillary
      and 18 (2%) with chromophobe renal cell carcinoma. Median followup for the 65
      patients who were still alive at last followup was 11.6 years. Patients with
      clear cell renal cell carcinoma were more likely to have metastasis to the lungs
      (53.6%) compared to those with papillary (33.3%) and chromophobe (33.3%) renal
      cell carcinoma (p = 0.012). Patients with chromophobe renal cell carcinoma were
      more likely to have metastasis to the liver compared to those with clear cell
      renal cell carcinoma (33.3% vs 9.7%, p = 0.007), but there was not a
      statistically significantly difference in the incidence of liver metastases
      between patients with chromophobe and papillary renal cell carcinoma (33.3% vs
      18.0%, p = 0.308). CONCLUSIONS: Site of distant metastasis varies significantly
      by renal cell carcinoma histological subtype. Patients with clear cell renal cell
      carcinoma are more likely to have metastasis to the lungs while patients with
      chromophobe renal cell carcinoma are more likely to experience liver metastasis.

PMID- 18076919
TI  - Cancer survivorship: challenges and changing paradigms.
AB  - PURPOSE: We summarize the potential issues faced by cancer survivors, define a
      conceptual framework for cancer survivorship, describe challenges associated with
      improving the quality of survivorship care and outline proposed survivorship
      programs that may be implemented going forward. MATERIALS AND METHODS: We
      performed a nonsystematic review of current cancer survivorship literature. Given
      the comprehensive scope and high profile, the recent report by the Institute of
      Medicine, From Cancer Patient to Cancer Survivor: Lost in Transition, served as
      the principal guide for the review. RESULTS: In recognition of the increasing
      number of cancer survivors in the United States survivorship has become an
      important health care concern. The recent report by the Institute of Medicine
      comprehensively outlined deficits in the care provided to cancer survivors, and
      proposed mechanisms to improve the coordination and quality of followup care for
      this increasing number of Americans. Measures to achieve these objectives include
      improving communication between health care providers through a survivorship care
      plan, providing evidence based surveillance guidelines and assessing different
      models of survivorship care. Implementing coordinated survivorship care broadly
      will require additional health care resources, and commitment from health care
      providers and payers. Research demonstrating the effectiveness of survivorship
      care will be important on this front. CONCLUSIONS: Potential shortcomings in the
      recognition and management of ongoing issues faced by cancer survivors may impact
      the overall quality of long-term care in this increasing population. Although
      programs to address these issues have been proposed, there is substantial work to
      be done in this area.

PMID- 18076921
TI  - Coordinated chemoradiation therapy with genital preservation for the treatment of
      primary invasive carcinoma of the male urethra.
AB  - PURPOSE: We evaluated the efficacy of a combined chemoradiation therapy protocol
      for the primary treatment of primary invasive carcinoma of the male urethra.
      MATERIALS AND METHODS: From January 1991 to December 2006, 18 patients with
      invasive carcinoma of the male urethra referred to our institution were treated
      with a chemoradiation therapy protocol, consisting of 2 cycles of 5-fluorouracil
      (1,000 mg/m(2)) on days 1 to 4 and days 29 to 32, and mitomycin-C (10 mg/m(2)) on
      days 1 and 29 with concurrent external beam radiation therapy (45 to 55 Gy in 25
      fractions during 5 weeks) to the genitalia, perineum, and inguinal and external
      iliac lymph nodes. Kaplan-Meier curves were constructed to assess overall,
      disease specific and disease-free survival. RESULTS: The stage and node
      distribution was T2N0 in 2 patients (11%), T3N0 in 8 (44%), T4N0 in 2 (11%), TXN1
      in 1(6%) and TXN2 in 5 (28%). The most prevalent histology was moderately (7 of
      18 patients or 39%) or poorly (10 of 18 or 56%) differentiated squamous cell
      carcinoma (17 of 18 or 95%). Overall 83% (15 of 18) of the patients had a
      complete response to the primary chemoradiation therapy protocol, and the 5-year
      overall and disease specific survival rates were 60% and 83%, respectively. Five
      year disease-free survival rates after chemoradiation therapy and after
      chemoradiation therapy with salvage surgery were 54% and 72%, respectively. The 3
      nonresponders died of disease after undergoing salvage surgery and 5 of the 15
      complete responders (30%) had recurrence. Complex urethral reconstruction was
      required in 3 of 10 patients (30%) who had prolonged disease-free survival.
      CONCLUSIONS: The chemoradiation therapy protocol is an alternative primary
      treatment modality for invasive urethral carcinoma. It enables an unprecedented
      potential for organ preservation.

PMID- 18076924
TI  - Untipped: an endourologist's lament (with apologies to Pete Seeger).

PMID- 18076926
TI  - Robotic simple prostatectomy.
AB  - PURPOSE: Minimally invasive approaches for large, symptomatic benign prostatic
      hyperplasia are replacing the gold standard open surgical approach, duplicating
      its results with lower morbidity. We describe our initial experience with robotic
      simple prostatectomy. MATERIALS AND METHODS: Since January 2007, robotic simple
      prostatectomy was performed via a transperitoneal approach in 7 patients with
      symptomatic significant prostatomegaly on transrectal ultrasound (mean 77.66 gm).
      Demographic, perioperative and outcome data were recorded and all procedures were
      performed by the same surgeon. RESULTS: Average patient age was 63.2 years (range
      56 to 72) and estimated blood loss was 298 ml (range 60 to 800). Average
      operative time was 205 minutes (range 120 to 300). Average hospital stay was 1.4
      days (range 1 to 2), average Foley catheter duration was 7 days (range 6 to 9)
      and drains were removed after an average of 3.75 days (range 3 to 4). Mean
      specimen weight on pathological examination was 50.48 gm (range 40 to 64.5).
      Transfusion was necessary in 1 patient. No complications were documented.
      Considerable improvement from baseline was noted in International Prostate
      Symptom Score (preoperative vs postoperative 22 vs 7.25) and maximum urine flow
      (preoperative vs postoperative 17.75 vs 55.5 ml per minute). Four patients were
      in acute urinary retention preoperatively. CONCLUSIONS: Robotic simple
      prostatectomy is a feasible, reproducible procedure. Further publications are
      expected with larger series and larger prostatic adenomas.

PMID- 18076928
TI  - Ureteral stenting and urinary stone management: a systematic review.
AB  - PURPOSE: Ureteral stents are widely used in many urological procedures. We
      evaluated the recent literature, providing an update on materials and stent
      designs, and indications for stent placement and stent complications, including
      the management of such stent related problems. MATERIALS AND METHODS: A thorough
      literature search on ureteral stents was performed. Pertinent new and
      review/updated articles published in the English literature from 2000 through
      2006 were systematically reviewed. RESULTS: Following uncomplicated ureteroscopy
      or shock wave lithotripsy routine stenting does not appear to affect the stone
      free rate. However, stent related morbidity is often seen. Patients at greatest
      risk for complications are those undergoing bilateral stentless ureteroscopy,
      those with recent or recurrent urinary tract infections and pregnant patients.
      The placement of indwelling stents in these patients should be considered. The
      development of stent materials and designs has been directed toward decreasing
      stent related morbidity, such as pain, discomfort, bladder irritability,
      infection and encrustation. Changes in stent design and materials show great
      promise. Initial evaluations suggest improvements in patient comfort as well as
      decreased encrustation. Forgotten stents can lead to significant morbidity as a
      result of severe encrustation. Most cases can be managed endoscopically, often
      requiring multiple procedures. CONCLUSIONS: Stenting is not mandatory after
      uncomplicated simple ureteroscopy and shock wave lithotripsy. Patients with
      stents seem to have significantly more bladder and lower urinary tract symptoms
      than those in whom stents are not placed. However, there is a subgroup of
      patients who likely benefit from stenting following a procedure because of the
      increased risk of complications. The ideal ureteral stent biomaterial has yet to
      be discovered and an area of promising development is the drug eluting stent to
      prevent infection and encrustation.

PMID- 18076929
TI  - Trends in the use of gross and frozen section pathological consultations during
      partial or radical nephrectomy for renal cell carcinoma.
AB  - PURPOSE: There is no consensus regarding the role of intraoperative pathological
      consultation during kidney cancer surgery. Accordingly intraoperative
      pathological consultation use is susceptible to variation based on nonclinical
      factors. We explored this hypothesis by evaluating national trends in the use of
      intraoperative pathological consultation during radical or partial nephrectomy
      with time, across regions, and by patient and provider characteristics. MATERIALS
      AND METHODS: Using linked Surveillance, Epidemiology and End Results-Medicare
      data we identified a cohort of patients who underwent partial or radical
      nephrectomy from 1991 to 2002. In each case we ascertained corresponding Medicare
      claims for gross and/or frozen section intraoperative pathological consultation.
      We assessed variations in the use of intraoperative pathological consultation by
      year of treatment and geographic region as well as by patient and provider
      characteristics. RESULTS: We identified 7,507 cases treated with partial (600 or
      8.0%) or radical (6,907 or 92.0%) nephrectomy from 1991 through 2002. Of cases
      treated with radical nephrectomy 744 (10.8%) and 843 (12.2%) received gross and
      frozen section intraoperative pathological consultation, respectively. Of cases
      treated with partial nephrectomy 67 (11.2%) had an intraoperative gross
      consultation and 323 (53.8%) had a frozen section evaluation. Use of
      intraoperative pathological consultation (gross or frozen section) during partial
      and radical nephrectomy varied based on patient demographics, United States
      Census region, and Surveillance, Epidemiology and End Results registry (p <0.05).
      Intraoperative pathological consultation during radical nephrectomy differed by
      year of treatment (p <0.05). Intraoperative pathological consultation use also
      varied based on provider characteristics (p <0.05). CONCLUSIONS: Intraoperative
      pathological consultation use during kidney cancer surgery varies with time,
      across geographic regions and based on patient demographics and broadly defined
      provider characteristics. These data provide context for future studies seeking
      to refine the use of intraoperative pathological consultation in this clinical
      setting.

PMID- 18076931
TI  - Radical nephrectomy for pT1a renal masses may be associated with decreased
      overall survival compared with partial nephrectomy.
AB  - PURPOSE: We reviewed our surgical experience with small renal tumors, comparing
      overall survival in patients treated with radical and partial nephrectomy.
      MATERIALS AND METHODS: Using our nephrectomy registry we identified patients with
      sporadic, unilateral, solitary and localized renal masses 4 cm or less who
      underwent radical or partial nephrectomy between 1989 and 2003. Patients with a
      solitary kidney or impaired renal function at presentation were excluded, leaving
      648 available for analysis. Overall survival was estimated using the Kaplan-Meier
      method and associations with death were evaluated using Cox proportional hazards
      regression. RESULTS: At last followup 146 patients had died of any cause and 502
      were alive at a median of 7.1 years. Radical and partial nephrectomy was
      performed in 290 and 358 patients, respectively. In all patients radical
      nephrectomy was not significantly associated with death from any cause compared
      with partial nephrectomy (RR 1.12, p = 0.52). However, there was a significant
      interaction with age, leading us to stratify our analysis at the median age of 65
      years. In 327 patients younger than 65 years radical nephrectomy was
      significantly associated with death from any cause compared with partial
      nephrectomy (RR 2.16, p = 0.02). The increased risk of death persisted after
      adjusting for year of surgery (p = 0.02), preoperative creatinine (p = 0.03),
      Charlson-Romano index (p = 0.04), symptoms at presentation (p = 0.02), diabetes
      at presentation (p = 0.03) and histology (p = 0.02). CONCLUSIONS: Our results
      suggest that, compared with partial nephrectomy, radical nephrectomy is
      associated with decreased overall survival in younger patients with small renal
      masses.

PMID- 18076932
TI  - The distribution of histological subtypes of renal tumors by decade of life using
      the 2004 WHO classification.
AB  - PURPOSE: The 2004 World Health Organization histological classification of renal
      tumors reflects our understanding of the underlying molecular determinants of
      renal tumors. We reviewed all partial and radical nephrectomy specimens at Barnes
      Jewish Hospital to determine if the distribution of renal tumor histological
      subtypes varies by decade of life using the new scheme. MATERIALS AND METHODS: A
      total of 1,043 consecutive cases of renal masses operated on for presumed
      malignancy from 1989 to 2003 were identified. All specimens were rereviewed by a
      single pathologist (MFS) and classified by the 2004 WHO scheme. In addition to
      decade of life and histological subtype, gender, tumor size and pathological
      tumor stage were analyzed. RESULTS: Analysis demonstrated an association between
      histological subtype and decade of life (p <0.001). The proportions of clear cell
      renal cell carcinoma (p = 0.008) and angiomyolipoma (p <0.001) decreased while
      the proportions of oncocytoma (p <0.001) and papillary renal cell carcinoma (p =
      0.005) increased with increasing decade of life. The proportions of chromophobe
      (p = 0.181) and unclassified (p = 0.660) renal cell carcinoma did not change with
      increasing decade of life. In addition, younger patients were more likely to have
      larger tumors (p = 0.019) and metastatic disease at diagnosis (p = 0.017), while
      gender (p = 0.809) and tumor stage (p = 0.334) were not associated with
      increasing decade of life. CONCLUSIONS: This study provides baseline histological
      subtypes by decade for the most common renal tumors using the 2004 WHO
      histological classification. Clinicians may consider using these trends along
      with imaging, history and physical examination to counsel patients before
      recommending treatment.

PMID- 18076933
TI  - Managing bone loss in men with locally advanced prostate cancer receiving
      androgen deprivation therapy.
AB  - PURPOSE: We reviewed the pathogenesis, diagnosis, prevalence, prevention and
      treatment of bone loss in patients with nonmetastatic prostate cancer receiving
      androgen deprivation therapy. MATERIALS AND METHODS: Using PubMed we performed a
      comprehensive literature search to identify articles on bone mineral density loss
      in patients with nonmetastatic prostate cancer receiving androgen deprivation
      therapy. Pertinent articles were reviewed and evaluated. RESULTS: Bone mineral
      density loss and related fractures were recently established as significant
      adverse events associated with androgen deprivation therapy. Patients with
      nonmetastatic prostate cancer receiving androgen deprivation therapy experience
      annual bone mineral density losses of 0.6% to 4.6% with the most significant loss
      within year 1 of therapy. In addition to calcium and vitamin D supplements,
      current treatment options for androgen deprivation therapy induced bone loss
      include synthetic estrogens, selective estrogen receptor modulators and
      bisphosphonates. Recent safety concerns have been identified, including renal
      dysfunction with intravenous bisphosphonates and osteonecrosis of the jaw with
      oral and intravenous bisphosphonates. However, minimal renal dysfunction and no
      cases of osteonecrosis of the jaw have been reported in this setting.
      CONCLUSIONS: Because the most significant bone mineral density loss occurs within
      year 1 of androgen deprivation therapy and most fractures in healthy men occur in
      those without osteoporosis, early intervention is warranted to prevent skeletal
      morbidity in patients with nonmetastatic prostate cancer receiving androgen
      deprivation therapy. Although the majority of and the most compelling evidence
      supports the use of bisphosphonates for preventing and treating androgen
      deprivation therapy induced bone loss, further study is needed to define the
      optimal regimen, timing of initiation and duration of therapy as well as long
      term efficacy and safety.

PMID- 18076934
TI  - Over expression of insulin-like growth factor binding protein 3 in clear cell
      renal cell carcinoma.
AB  - PURPOSE: We recently reported that IGFBP-3 (insulin-like growth factor binding
      protein 3) is one of the top genes that are over expressed in clear cell renal
      cell carcinoma. We further investigated IGFBP-3 expression in renal tumors using
      gene expression microarrays, immunohistochemistry and Western blotting. MATERIALS
      AND METHODS: A total of 70 renal neoplasms were subjected to gene expression
      microarrays using gene chips containing 21,632 cDNA clones. IGFBP-3 expression
      was measured in each renal epithelial neoplasm. In addition, we performed
      immunohistochemistry for IGFBP-3 in 127 renal epithelial tumors, including 58
      clear cell renal cell carcinomas. Moreover, IGFBP-3 staining intensity was
      evaluated to determine whether there was a correlation with Fuhrman grade.
      Lastly, Western blot was performed to confirm IGFBP-3 levels. RESULTS: On
      microarray analysis of 70 renal neoplasms IGFBP-3 mRNA was increased in 63% of
      clear cell renal cell carcinomas (27 of 43) but in only 4% of other renal tumors
      (1 of 24). On immunohistochemistry 74% of clear cell renal cell carcinomas (43 of
      58) showed IGFBP-3 immunoreactivity compared to only 9% of other renal neoplasms
      (6 of 69). High grade (Fuhrman grades 3 and 4) clear cell renal cell carcinomas
      showed higher IGFBP-3 staining intensity than low grade ones (15 of 17 vs 8 of
      41). Western blot confirmed immunohistochemistry findings with the detection of
      high IGFBP-3 in clear cell renal cell carcinoma but not in other types of kidney
      tumors. CONCLUSIONS: With a combination of cDNA microarrays, Western blot and
      immunohistochemistry we confirmed that IGFBP-3 is a marker for clear cell renal
      cell carcinoma. Furthermore, higher IGFBP-3 expression was associated with higher
      Fuhrman grade.

PMID- 18076936
TI  - Role of urinary cathepsin B and L in the detection of bladder urothelial cell
      carcinoma.
AB  - PURPOSE: We tested the hypothesis that urinary cathepsin B and L are associated
      with bladder cancer recurrence and invasiveness in patients with a history of
      nonmuscle invasive urothelial carcinoma of the bladder. MATERIALS AND METHODS:
      Cathepsin B and L, and NMP22 were determined in the urine specimens of 188
      consecutive subjects with a history of treated urothelial carcinoma of the
      bladder, 31 with noncancerous urological conditions and 10 healthy subjects.
      Cathepsin B and L were analyzed as continuous and categorical variables based on
      their quartile distribution. RESULTS: Urinary cathepsin L was higher in the 122
      patients with cystoscopic evidence of bladder tumor compared with levels in 107
      with normal cystoscopy (median 5.9, IQR 4.4 vs 3.0, IQR 3.2, p <0.001). Higher
      levels of cathepsin L were associated with positive cytology assay results,
      higher NMP22 and T1 or greater pathological stage (each p <0.001). Area under the
      ROC curves of NMP22 and cathepsin L for bladder cancer detection were 0.704 (95%
      CI 0.637-0.772) and 0.793 (95% CI 0.736-0.850), respectively. On multivariate
      analysis cathepsin L, NMP22 and cytology were associated with invasive
      pathological stage (OR 1.29, 2.42 and 2.76, respectively, p </=0.002). Urinary
      cathepsin B was not associated with any outcome variables. CONCLUSIONS: Urinary
      cathepsin L is an independent predictor of bladder cancer presence and
      invasiveness in patients with a history of urothelial carcinoma of the bladder.
      Further evaluation of this marker is necessary before its use as an adjunct to
      cystoscopy for urothelial carcinoma of the bladder.

PMID- 18076937
TI  - Vesicoureteral reflux: the RIVUR study and the way forward.

PMID- 18076938
TI  - The role of pelvic lymphadenectomy for prostate cancer--therapeutic?
AB  - PURPOSE: The incidence of metastatic lymph node involvement in prostate cancer
      has decreased with the advent of prostate specific antigen testing. Various
      algorithms have been designed to assess the probability of lymphatic involvement,
      resulting in the omission of lymph node dissection in many cases. However, recent
      reports suggest an underestimation of lymph node involvement. Meticulous lymph
      node dissection may provide a survival benefit by addressing micrometastatic
      disease. We analyzed the current literature on extended pelvic lymphadenectomy in
      prostate cancer. MATERIAL AND METHODS: The pelvic lymphadenectomy literature was
      reviewed using a MEDLINE search, focusing on the prevalence of positive nodes,
      staging vs extended lymphadenectomy and therapeutic benefits. RESULTS: Staging
      pelvic lymphadenectomy provides valuable prognostic data and it may be
      therapeutic. Extended lymph node dissection increases the detection of positive
      nodes. The number of positive or negative nodes resected may increase survival.
      The observed survival benefits may be due to the elimination of micrometastatic
      disease. CONCLUSIONS: The role, indications and extent of lymphadenectomy remain
      controversial. Extended lymph node dissection should be performed in all patients
      at high risk to increase staging accuracy and provide a potential survival
      benefit. Detailed, meticulous dissection of the internal iliac lymph tissue is
      required. The benefit of extended lymph node dissection in patients at low risk
      remains to be determined.

PMID- 18076941
TI  - CpG island hypermethylation profile in the serum of men with clinically localized
      and hormone refractory metastatic prostate cancer.
AB  - PURPOSE: We have noted that hypermethylation at GSTP1 in the preoperative serum
      of men with localized prostate cancer predicts early prostate specific antigen
      failure following surgical treatment. In this study we investigated the
      hypermethylation profile of several genes in the serum of men with localized and
      hormone refractory prostate cancer. MATERIALS AND METHODS: We assayed the serum
      of 192 men with clinically localized prostate cancer and 18 with hormone
      refractory metastatic disease. A total of 35 serum samples from patients with
      negative prostate biopsy served as a negative control. CpG Island
      hypermethylation status of certain genes was assessed, including MDR1, EDNRB,
      CD44, NEP, PTGS2, RASSF1A, RAR-beta and ESR1. The results of hypermethylation at
      GSTP1 were included from a previous study. RESULTS: CpG island hypermethylation
      at MDR1 was positive in 38.2% of cases without PSA recurrence and in 16.1% of
      those with biochemical recurrence after radical prostatectomy. DNA
      hypermethylation at the remaining 7 gene loci was not detected in the serum of
      patients with localized prostate cancer. In serum from metastatic prostate cancer
      cases CpG island hypermethylation was detected at MDR1 in 15 (83.3%), EDNRB in 9
      (50%), RAR-beta in 7 (38.9%), GTSP1 in 5 (27.8%) and NEP or RASSF1A in 3 (16.7%).
      CpG island hypermethylation at CD44, PTGS2 or ESR was not detected in any
      samples. All histologically normal cases were negative for CpG island
      hypermethylation. CONCLUSIONS: DNA hypermethylation at MDR1 was detected in cases
      of localized prostate cancer. CpG island hypermethylation at several gene loci
      was detected in men with advanced disease. No single gene was consistently
      observed to be hypermethylated in men with hormone refractory disease. These
      results suggest that the CpG island hypermethylation status of a defined panel of
      genes may be a useful biomarker in men with hormone refractory prostate cancer.

PMID- 18076946
TI  - Renal vein ostium wall invasion of renal cell carcinoma with an inferior vena
      cava tumor thrombus: prediction by renal and vena caval vein diameters and
      prognostic significance.
AB  - PURPOSE: We determined whether renal vein ostium wall invasion could be predicted
      by renal vein and inferior vena cava diameter on imaging. We also determined
      whether it is a prognostic factor for recurrence and survival after radical
      nephrectomy and thrombus ablation for renal cell carcinoma with an inferior vena
      cava tumor thrombus. MATERIALS AND METHODS: From January 2000 to January 2006
      nephrectomy for renal cell carcinoma was performed in 446 patients, of whom 32
      (7.2%) underwent inferior vena cava thrombus extraction with complete resection
      of the renal vein ostium. When necessary, inferior vena cava partial and
      circumferential ablation was done in 5 and 8 patients, respectively, as well as
      replacement for thrombus adhesions. The largest coronal or axial diameter of the
      renal vein ostium and inferior vena cava anteroposterior diameter were measured
      on preoperative magnetic resonance imaging. Renal vein ostium wall invasion was
      assessed in all patients and determined microscopically by tumor cell
      infiltration into the intima. ROC curves were used to assess the value of these
      measurements for diagnosing patients with renal vein ostium invasion with 90%
      sensitivity. The risk of recurrence and survival was analyzed. RESULTS: Renal
      vein ostium wall invasion was present in 13 of 32 patients (40.6%). It
      significantly correlated with mean +/- SD inferior vena cava anteroposterior
      diameter (27.8 +/- 10.2 vs 17.3 +/- 6.8 mm, p = 0.01) and with the largest mean
      renal vein ostium diameter (22.3 +/- 7.9 vs 12.6 +/- 6.9 mm, p = 0.01). The upper
      level of the inferior vena cava thrombus correlated with renal vein ostium
      invasion (p = 0.002). The inferior vena cava anteroposterior diameter or renal
      vein ostium diameter cutoff value to predict wall invasion with 90% sensitivity
      was 18 and 14 mm, respectively. The AUC was 0.78 for inferior vena cava diameter
      and 0.86 for renal vein ostium diameter. No inferior vena cava recurrence was
      observed. Renal vein ostium wall invasion was associated with a higher risk of
      recurrence and decreased specific survival (p = 0.01 and 0.03, respectively). The
      association of ostium renal vein wall invasion with death from renal cell
      carcinoma was seen on multivariate analysis after adjusting for tumor size, TNM
      stage and thrombus level (RR 5.9, 95% CI 1.45-30.8, p = 0.01). CONCLUSIONS:
      Preoperative imaging measurements of renal vein and inferior vena cava diameter
      can accurately predict renal vein ostium wall invasion. Renal vein ostium wall
      invasion is an independent prognostic marker that is associated with a higher
      risk of recurrence and decreased specific survival.

PMID- 18076947
TI  - The 20-core prostate biopsy protocol--a new gold standard?
AB  - PURPOSE: We investigated the ability of a 20-core prostate biopsy protocol to
      enhance the prostate cancer diagnosis rate. MATERIALS AND METHODS: We compared
      the diagnosis rate of prostate biopsies in 2 groups of consecutive patients,
      including group 1-10 cores and group 2-20 cores. The prostate specific antigen
      range in the 2 groups was 3 to 30 ng/ml and biopsies were performed because of
      increased prostate specific antigen (more than 3 ng/ml) and/or abnormal digital
      rectal examination. To analyze the results we divided each group into 3 subgroups
      according to prostate specific antigen, including group 1-3 to less than 6 ng/ml,
      group 2-6 or greater to less than 10 ng/ml and group 3-10 or greater to up to 30
      ng/ml. Multivariate analysis was performed to assess the difference in the
      diagnosis rate among the subgroups according to the number of cores taken.
      RESULTS: The percent of positive biopsies was 39.7% in group 1 and 51.7% in group
      2. Multivariate analysis confirmed that the number of biopsies taken was a factor
      that independently and significantly correlated with the prostate cancer
      diagnosis. The 20-core biopsy protocol was more efficient than the 10-core
      protocol in the 3 subgroups with 47.2% vs 28.1% of patients diagnosed in group 1
      (OR 3.26, p = 0.001), 40.5% vs 36.1% in group 2 (OR 2.37, p = 0.009) and 69.8% vs
      39.7% in group 3 (OR 2.01, p = 0.015). CONCLUSIONS: The 20-core biopsy protocol
      was more efficient than the 10-core biopsy protocol, especially in patients with
      prostate specific antigen between 3 and 6 ng/ml. Nevertheless, it is mandatory to
      confirm whether detected tumors are clinically significant on pathological
      examination of the radical prostatectomy specimens.

PMID- 18076949
TI  - Significance of tertiary Gleason pattern 5 in Gleason score 7 radical
      prostatectomy specimens.
AB  - PURPOSE: The Gleason grading system in reporting prostate cancer accounts for the
      primary and secondary Gleason pattern. The clinical significance of a higher
      tertiary (third most prevalent) grade is largely unrecognized. MATERIALS AND
      METHODS: Radical prostatectomy specimens from 300 patients with Gleason score 7
      (3 + 4 or 4 + 3) prostate cancer were pathologically reexamined for the presence
      of a tertiary grade 5 pattern as well as the association with pathological stage
      and biochemical recurrence-free survival. RESULTS: A total of 214 patients met
      study inclusion criteria. Patients with Gleason score 7 and tertiary grade 5
      cancer had significantly higher pathological stage disease than patients with
      Gleason score 7 without tertiary grade 5 cancer (p <0.001). Gleason score 7 +
      tertiary pattern 5 tumors were significantly associated with adverse pathological
      features such as seminal vesicle invasion, extraprostatic extension and
      lymphovascular invasion compared to Gleason score 7 tumors (p <0.05). The
      relative effects of a tertiary grade 5 component on all pathological parameters
      analyzed was greater for Gleason score 7 tumors with a lower primary Gleason
      pattern 3 vs a higher primary Gleason pattern 4. Patients with Gleason score 7 +
      tertiary pattern 5 tumors had significantly decreased biochemical recurrence-free
      survival (54 months) compared to patients with Gleason score 7 tumors (121
      months) (p = 0.0005). Preoperative prostate specific antigen, lymphovascular
      invasion and positive surgical margin status were shown to be independent
      predictors of prostate specific antigen recurrence on multivariate analysis.
      CONCLUSIONS: Small percentages of tertiary grade 5 patterns in Gleason score 7
      radical prostatectomy specimens are associated with aggressive pathological
      features predictive of advanced pathological stage and biochemical recurrence
      free survival.

PMID- 18076950
TI  - Modern bariatric surgery and nephrolithiasis--are we on the verge of a new
      epidemic?

PMID- 18076952
TI  - Small transrectal ultrasound volume predicts clinically significant Gleason score
      upgrading after radical prostatectomy: results from the SEARCH database.
AB  - PURPOSE: Needle biopsy Gleason scores are often upgraded after pathological
      examination of the prostate following radical prostatectomy. It has been
      suggested that larger prostates would be associated with a greater risk of
      upgrading since a smaller percentage of the gland is sampled and, thus, the
      highest grade disease would more likely be missed, assuming an equal number of
      cores is taken from similar locations. We examined the likelihood of clinically
      relevant upgrading after radical prostatectomy as a function of transrectal
      ultrasound volume. MATERIALS AND METHODS: We examined the association between
      transrectal ultrasound volume and upgrading (higher Gleason score category in the
      radical prostatectomy specimen than in the biopsy) in 586 men treated with
      radical prostatectomy between 1995 and 2006 in the SEARCH database who underwent
      at least a sextant biopsy using multivariate logistic regression. Transrectal
      ultrasound volume was categorized as 20 or less (in 71), 21 to 40 (in 334), 41 to
      60 (in 123) and greater than 60 cm(3) (in 58). Gleason score was examined as a
      categorical variable of 2-6, 3 + 4 and 4 + 3 or greater. RESULTS: Overall 138
      cases (24%) were upgraded, 80 (14%) were downgraded, and 368 (62%) had identical
      biopsy and pathological Gleason sum groups. Larger transrectal ultrasound volume
      was significantly associated with decreased likelihood of upgrading (p trend
      <0.001). For transrectal ultrasound volumes greater than 60, 41 to 60, 21 to 40
      and 20 cm(3) or less, the estimated multivariate adjusted probability of
      upgrading was 12.6%, 27.5%, 36.4% and 45.5% for Gleason 2-6 tumors, and 6.1%,
      8.5%, 18.9% and 20.9% for Gleason 3 + 4 tumors, respectively. CONCLUSIONS: Larger
      transrectal ultrasound volumes were at decreased risk for clinically significant
      upgrading after radical prostatectomy. This fact should be kept in mind when
      deciding on treatment decisions for men with apparently low grade prostate cancer
      on biopsy.

PMID- 18076955
TI  - Unimpaired sentence comprehension after anterior temporal cortex resection.
AB  - Functional imaging studies have demonstrated involvement of the anterior temporal
      cortex in sentence comprehension. It is unclear, however, whether the anterior
      temporal cortex is essential for this function. We studied two aspects of
      sentence comprehension, namely syntactic and prosodic comprehension in temporal
      lobe epilepsy patients who were candidates for resection of the anterior temporal
      lobe. METHODS: Temporal lobe epilepsy patients (n=32) with normal (left) language
      dominance were tested on syntactic and prosodic comprehension before and after
      removal of the anterior temporal cortex. The prosodic comprehension test was also
      compared with performance of healthy control subjects (n=47) before surgery.
      RESULTS: Overall, temporal lobe epilepsy patients did not differ from healthy
      controls in syntactic and prosodic comprehension before surgery. They did perform
      less well on an affective prosody task. Post-operative testing revealed that
      syntactic and prosodic comprehension did not change after removal of the anterior
      temporal cortex. DISCUSSION: The unchanged performance on syntactic and prosodic
      comprehension after removal of the anterior temporal cortex suggests that this
      area is not indispensable for sentence comprehension functions in temporal
      epilepsy patients. Potential implications for the postulated role of the anterior
      temporal lobe in the healthy brain are discussed.

PMID- 18076957
TI  - Quinolone alkaloids from Waltheria douradinha.
AB  - A phytochemical investigation of the stems of Waltheria douradinha resulted in
      isolation of two 4-quinolone alkaloids, waltherione B and vanessine, along with
      three known alkaloids, waltherione A, antidesmone and O-methyltembamide. Their
      structures were elucidated on the basis of their 2D NMR spectroscopic analyses,
      and from X-ray crystallographic analysis of waltherione A and the O-methyl
      derivative of waltherione B. Additionally, waltherione B and vanessine, and the O
      and N-methyl derivatives of waltherione A and waltherione B, were evaluated for
      their antimicrobial activities; only vanessine displayed any (weak) antimicrobial
      activity.

PMID- 18076956
TI  - Some effects of CB1 antagonists with inverse agonist and neutral biochemical
      properties.
AB  - The CB1 inverse agonist/antagonist SR141716A recently has been introduced for the
      management of obesity (rimonabant; Acomplia) and appears to have beneficial
      effects. However, its utility may be hampered in some individuals by adverse
      effects including nausea or emesis or by mood depression. The recent development
      of biochemically 'neutral' antagonists such as AM4113 (Sink et al., 2007) has
      allowed an initial evaluation of the proposition that adverse effects of
      SR141716A are associated with its inverse agonist activity. Thus far, data
      comparing SR141716A and AM4113 across several species indicate that both drugs
      produce dose-related direct effects on operant behavior within the same range of
      doses that serve to antagonize the behavioral and hypothermic effects of a CB1
      agonist. However, initial observations suggest that AM4113 may not produce
      preclinical indications of nausea or emesis. Further studies with AM4113 and
      other novel CB1 antagonists differing in efficacy should amplify our
      understanding of the relationship between the pharmacological activity of CB1
      antagonists and their behavioral effects.

PMID- 18076958
TI  - Serotonin receptor 1B (HTR1B) genotype associated with milk production traits in
      cattle.
AB  - Serotonin receptor 1B (HTR1B) is one of the 14 different identified serotonin
      receptors which are involved in the regulation of behaviors such as sleep, fear,
      aggression, mood, and feeding. The aims of this study were to characterize
      polymorphisms in the 5' coding and the 3' flanking regions of the bovine HTR1B
      gene among Chinese Holsteins and to identify the association of HTR1B
      polymorphisms with milk production performance. SSCP was used to examine the
      polymorphisms at four loci and the fragments with different SSCP patterns were
      sequenced. A total of three single nucleotide polymorphisms (SNPs) were detected,
      among which the 205G>T mutation was found to cause a predicted amino acid change:
      from Ala to Ser at position 69. The polymorphism of G205T was identified to be
      associated with milk yield trait. Furthermore, the H1-C genotype was found to be
      associated with a significant increase in milk yield of 489kg vs. the H1-A
      genotype (P<0.05).

PMID- 18076959
TI  - Mutual enhancement of central neurotoxicity induced by ketamine followed by
      methamphetamine.
AB  - We hereby report that repeated administration of ketamine (350 mg/kg in total)
      and methamphetamine (30 mg/kg in total) causes specific glutamatergic and
      dopaminergic neuron deficits, respectively, in adult mouse brain. Acute ketamine
      did not affect basal body temperature or the later methamphetamine-induced
      hyperthermia. However, pretreatment with repeated doses of ketamine aggravated
      methamphetamine-induced dopaminergic terminal loss as evidenced by a drastic
      decrease in the levels of dopamine, 3,4-dihydroxyphenylacetic acid, and dopamine
      transporter density as well as poor gait balance performance. In contrast,
      methamphetamine-induced serotonergic depletion was not altered by ketamine
      pretreatment. Likewise, the subsequent treatment with methamphetamine exacerbated
      the ketamine-induced glutamatergic damage as indicated by reduced levels of the
      vesicular glutamate transporter in hippocampus and striatum and poor memory
      performance in the Morris water maze. Finally, since activation of the D1 and
      AMPA/kainate receptors has been known to be involved in the release of glutamate
      and dopamine, we examined the effects of co-administration of SCH23390, a D1
      antagonist, and CNQX, an AMPA/kainate antagonist. Intraventricular CNQX infusion
      abolished ketamine's potentiation of methamphetamine-induced dopamine
      neurotoxicity, while systemic SCH23390 mitigated methamphetamine's potentiation
      of ketamine-induced glutamatergic toxicity. We conclude that repeated doses of
      ketamine potentiate methamphetamine-induced dopamine neurotoxicity via
      AMPA/kainate activation and that conjunctive use of methamphetamine aggravates
      ketamine-induced glutamatergic neurotoxicity possibly via D1 receptor activation.

PMID- 18076961
TI  - Normal cadmium uptake in microcytic anemia mk/mk mice suggests that DMT1 is not
      the only cadmium transporter in vivo.
AB  - Divalent metal transporter 1 (DMT1) is a mammalian iron (Fe) transporter and also
      transports Cadmium (Cd) in vitro. This study compared Cd absorption in DMT1
      dysfunctional MK/Rej-(mk)/(mk) mice (mk/mk mice) and in DMT1-functional, Fe
      deficient wild-type (WT) mice, to clarify the role of DMT1 in intestinal Cd
      absorption in vivo. Mice were given 1 ppm CdCl2 aq in drinking water for 2 weeks,
      and the concentrations of Cd and Fe in liver, kidney, and intestinal epithelium
      were subsequently determined. The Fe concentration in intestinal epithelia of WT
      mice was decreased in proportion to the level of dietary Fe limitation, while Cd
      accumulation under the same conditions was increased. DMT1 mRNA expression in the
      small intestine of Fe-deficient WT mice was clearly increased compared to that in
      Fe-sufficient WT mice. Iron deficiency resulted in up-regulation of Cd uptake in
      the intestine of Fe-deficient WT mice. The mk/mk mice have a mutation in DMT1 and
      loss of its function led to decreased intestinal Fe concentration. However,
      intestinal Cd accumulation was the same as in WT mice and it was also increased
      in Fe-deficient situation. There is the possibility that an unknown Cd pathway
      has taken a role on Cd intestinal absorption in vivo and that this pathway is
      regulated by food Fe concentrations. Therefore, DMT1 is not the sole transporter
      of intestinal cadmium absorption in vivo.

PMID- 18076960
TI  - Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the
      morphogenic activity of acetylcholinesterase.
AB  - A primary role of acetylcholinesterase (AChE) is regulation of cholinergic
      neurotransmission by hydrolysis of synaptic acetylcholine. In the developing
      nervous system, however, AChE also functions as a morphogenic factor to promote
      axonal growth. This raises the question of whether organophosphorus pesticides
      (OPs) that are known to selectively bind to and inactivate the enzymatic function
      of AChE also interfere with its morphogenic function to perturb axonogenesis. To
      test this hypothesis, we exposed primary cultures of sensory neurons derived from
      embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon
      metabolite (CPFO). Both OPs significantly decreased axonal length at
      concentrations that had no effect on cell viability, protein synthesis or the
      enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO
      on axonal growth in DRG neurons cultured from AChE nullizygous (AChE -/-) versus
      wild type (AChE +/+) mice indicated that while these OPs inhibited axonal growth
      in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE -/- DRG
      neurons. However, transfection of AChE -/- DRG neurons with cDNA encoding full
      length AChE restored the wild type response to the axon inhibitory effects of
      OPs. These data indicate that inhibition of axonal growth by OPs requires AChE,
      but the mechanism involves inhibition of the morphogenic rather than enzymatic
      activity of AChE. These findings suggest a novel mechanism for explaining not
      only the functional deficits observed in children and animals following
      developmental exposure to OPs, but also the increased vulnerability of the
      developing nervous system to OPs.

PMID- 18076962
TI  - Development and characterization of P-glycoprotein 1 (Pgp1, ABCB1)-mediated
      doxorubicin-resistant PLHC-1 hepatoma fish cell line.
AB  - The development of the multidrug resistance (MDR) phenotype in mammals is often
      mediated by the overexpression of the P-glycoprotein1 (Pgp, ABCB1) or multidrug
      resistance-associated protein (MRP)-like ABC transport proteins. A similar
      phenomenon has also been observed and considered as an important part of the
      multixenobiotic resistance (MXR) defence system in aquatic organisms. We have
      recently demonstrated the presence of ABC transporters in the widely used in
      vitro fish model, the PLHC-1 hepatoma cell line. In the present study we were
      able to select a highly resistant PLHC-1 sub-clone (PLHC-1/dox) by culturing the
      wild-type cells in the presence of 1 microM doxorubicin. Using quantitative PCR a
      42-fold higher expression of ABCB1 gene was determined in the PLHC-1/dox cells
      compared to non-selected wild-type cells (PLHC-1/wt). The efflux rates of model
      fluorescent Pgp1 substrates rhodamine 123 and calcein-AM were 3- to 4-fold higher
      in the PLHC-1/dox in comparison to the PLHC-1/wt cells. PLHC-1/dox were 45-fold
      more resistant to doxorubicin cytotoxicity than PLHC-1/wt. Similarly to mammalian
      cell lines, typical cross-resistance to cytotoxicity of other chemotherapeutics
      such as daunorubicin, vincristine, vinblastine, etoposide and colchicine,
      occurred. Furthermore, cyclosporine A, verapamil and PSC833, specific inhibitors
      of Pgp1 transport activity, completely reversed resistance of PLHC-1/dox cells to
      all tested drugs, resulting in EC50 values similar to the EC50 values found for
      PLHC-1/wt. In contrast, MK571, a specific inhibitor of MRP type of efflux
      transporters, sensitized PLHC-1/dox cells, neither to doxorubicin, nor to any
      other of the chemotherapeutics used in the study. These data demonstrate for the
      first time that a specific Pgp1-mediated doxorubicin resistance mechanism is
      present in the PLHC-1 fish hepatoma cell line. In addition, the fact that low
      micromolar concentrations of specific inhibitors may completely reverse a highly
      expressed doxorubicin resistance points to the fragility of Pgp1-mediated MXR
      defence mechanism in fish.

PMID- 18076963
TI  - Development of an adenoviral vector with robust expression driven by p53.
AB  - Here we introduce a new adenoviral vector where transgene expression is driven by
      p53. We first developed a synthetic promoter, referred to as PGTxbeta, containing
      a p53-responsive element, a minimal promoter and the first intron of the rabbit
      beta-globin gene. Initial assays using plasmid-based vectors indicated that
      expression was tightly controlled by p53 and was 5-fold stronger than the
      constitutive CMV immediate early promoter/enhancer. The adenoviral vector, AdPG,
      was also shown to offer p53-responsive expression in prostate carcinoma cells
      LNCaP (wt p53), DU-145 (temperature sensitive mutant of p53) and PC3 (p53-null,
      but engineered to express temperature-sensitive p53 mutants). AdPG served as a
      sensor of p53 activity in LNCaP cells treated with chemotherapeutic agents. Since
      p53 can be induced by radiotherapy and chemotherapy, this new vector could be
      further developed for use in combination with conventional therapies to bring
      about cooperation between the genetic and pharmacologic treatment modalities.

PMID- 18076964
TI  - Molecular cloning and functional characterization of the human endogenous
      retrovirus K113.
AB  - The human endogenous retrovirus-K113 (HERV-K113) is the most complete HERV known
      to date. It contains open reading frames for all viral proteins. Depending on
      ethnicity, up to 30% of the human population carries the provirus on chromosome
      19. To facilitate molecular and functional studies, we have cloned the HERV-K113
      sequence into a small plasmid vector and characterized its functional properties.
      Here we show that based on a substantial LTR-promoter activity, full length
      messenger RNA and spliced env-, rec- and 1.5 kb (hel)-transcripts are produced.
      The envelope protein of HERV-K113 is synthesized as an 85 kDa precursor that is
      found partially processed. The accessory Rec protein is highly expressed and
      accumulates in the nucleus. Expression analysis revealed synthesis of the Gag
      precursor and the protease. However, the cloned HERV-K113 provirus is not
      replication competent. It carries inactivating mutations in the reverse
      transcriptase gene. These mutations can be reversed to reconstitute the active
      enzyme, but the reversion is not sufficient to reconstitute replication capacity
      of the virus.

PMID- 18076965
TI  - The herpes simplex virus receptor nectin-1 is down-regulated after trans
      interaction with glycoprotein D.
AB  - During herpes simplex virus (HSV) entry, membrane fusion occurs either on the
      cell surface or after virus endocytosis. In both cases, binding of glycoprotein D
      (gD) to a receptor such as nectin-1 or HVEM is required. In this study, we co
      cultured cells expressing gD with nectin-1 expressing cells to investigate the
      effects of gD on nectin-1 at cell contacts. After overnight co-cultures with gD
      expressing cells, there was a down-regulation of nectin-1 in B78H1-C10, SY5Y,
      A431 and HeLa cells, which HSV enters by endocytosis. In contrast, on Vero cells,
      which HSV enters at the plasma membrane, nectin-1 was not down-regulated. Further
      analysis of B78H1-derived cells showed that nectin-1 down-regulation corresponds
      to the ability of gD to bind nectin-1 and is achieved by internalization and low
      pH-dependent degradation of nectin-1. Moreover, gD is necessary for virion
      internalization in B78H1 cells expressing nectin-1. These data suggest that the
      determinants of gD-mediated internalization of nectin-1 may direct HSV to an
      endocytic pathway during entry.

PMID- 18076967
TI  - Aging and visual processing: declines in spatial not temporal integration.
AB  - Age-related declines in vision are well documented in the literature. In the
      present study we examined whether changes in spatial or temporal integration
      contribute to this decline. Younger (mean age of 21) and older (mean age of 745)
      subjects were asked to identify 2D shapes based on kinetic occlusion information-
      -the accretion and deletion of texture during motion. The results of the first
      experiment indicated age-related decrements in spatial but not temporal
      integration. In the second experiment we manipulated the lifetime of motion
      stimuli to more directly examine temporal integration. The results indicated no
      differential effect of age on temporal integration. The results considered
      together suggest age related changes in recovering 2D shape from occlusion are
      the result of spatial but not temporal integration. Age-related changes in neural
      inhibition and ACh for regulating spatial integration are proposed as possible
      mechanisms for this decline.

PMID- 18076966
TI  - On the flexibility of sustained attention and its effects on a texture
      segmentation task.
AB  - Previously we have shown that transient attention--the more automatic, stimulus
      driven component of spatial attention--enhances spatial resolution. Specifically,
      transient attention improves texture segmentation at the periphery, where spatial
      resolution is too low, but impairs performance at central locations, where
      spatial resolution is already too high for the task. In the present study we
      investigated whether sustained attention--the more controlled component of
      spatial attention-can also affect texture segmentation, and if so whether its
      effect will be similar to that of transient attention. To that end we combined
      central, symbolic cues with texture displays in which the target appears at
      several eccentricities. We found that sustained attention can also affect texture
      segmentation, but unlike transient attention, sustained attention improved
      performance at all eccentricities. Comparing the effect of pre-cues and post-cues
      indicated that the benefit brought about by sustained attention is significantly
      greater than the effect of location uncertainty reduction. These findings
      indicate that sustained attention is a more flexible mechanism that can optimize
      performance at all eccentricities in a task where performance is constrained by
      spatial resolution.

PMID- 18076968
TI  - Stabilisation of MSWI bottom ash with sulphide-rich anaerobic effluent.
AB  - Effluent of an anaerobic sulphate-reducing wastewater treatment process was used
      to stabilise bottom ash. The effect of stabilisation on the concentration and
      binding of Ca, P, S, Cu, Pb, Zn, As, Cr, and Mo were studied by comparing results
      of sequential extraction from fresh and stabilised bottom ash. The stabilisation
      treatment improved the retention of Ca, Cu, Pb, S, and Zn in bottom ash compared
      to a treatment with ion-exchanged water. In addition to retention, Cu, S, and Zn
      were accumulated from the anaerobic effluent in the bottom ash. Concentrations of
      As, Cr, and Mo remained on the same level, whereas leaching of P increased
      compared to control treatment with ion-exchanged water. Improved retention and
      accumulation were the result of increased binding to less soluble fractions. The
      highest increases were in the sulphide and organic carbon bound fraction and in
      the carbonate fraction. Enhanced carbonation was probably due to CO2 deriving
      from the degradation of organic carbon. Flushing of stabilised bottom ash with
      ion-exchanged water ensured that the observed changes were not easily reversed.
      Most of the sulphide in the anaerobic effluent was removed when it was passed
      through bottom ash. The objective was to study the feasibility of sulphide-rich
      anaerobic effluent in bottom ash stabilisation and changes in the binding of the
      elements during stabilisation. In addition, the ability of the process to remove
      sulphide from the effluent was observed.

PMID- 18076969
TI  - Bioaugmentation of aerobic microbial granules with Pseudomonas putida carrying
      TOL plasmid.
AB  - This paper describes results of a successful bioaugmentation experiment on
      aerobic granular sludge using Pseudomonas putida KT2442 cells bearing the TOL
      (pWWO) plasmid. The methodology was designed to monitor incorporation of the
      added donor cells into pre-existent microbial granules and the subsequent plasmid
      transfer to the autochthonous microbial community using shake flask microcosms.
      Expression of reporter proteins (GFP and DsRed) allowed in situ monitoring of
      donor cell attachment and plasmid transfer to the recipient cells using confocal
      laser scanning microscopy. Concomitant with donor integration and transconjugant
      proliferation in the granules, a significant increase in degradation of benzyl
      alcohol (used as sole substrate) was observed in the augmented microcosms. In
      contrast, control microcosms (with non-augmented granules) did not show any
      noticeable increase in the degradation of the substrate. This study shows that
      bioaugmentation of aerobic granular sludge via donor colonization and plasmid
      transfer is feasible for enhanced biodegradation.

PMID- 18076970
TI  - Time trend of hexabromocyclododecane in the breast milk of Japanese women.
AB  - Hexabromocyclododecane (HBCD) is a type of brominated flame retardant. We
      investigated the time trend of the stereoisomer-specific concentrations of HBCD
      (alpha, beta, and gamma) in breast milk samples of Japanese women by using liquid
      chromatography-tandem mass spectrometry (LC/MS/MS). The pooled milk lipid samples
      collected in 1973, 1978, 1983, 1988, 1993, 1999, and from 2000 to 2006 were
      analysed. The concentration was below the detection limit in the samples
      collected between 1973 and 1983 and increased in those collected since 1988.
      Between 1988 and 2006, alpha-HBCD was detected in all 11 breast milk samples
      collected from 25 to 29-year-old Japanese women; gamma-HBCD, in 7; and beta-HBCD,
      in none of the samples. Time trend of summation operatorHBCD appeared to be
      related to that of the industrial HBCD consumption level in Japan.

PMID- 18076971
TI  - Photolysis of 14C-sulfadiazine in water and manure.
AB  - Photolysis of 14C-sulfadiazine in aqueous solution under simulated sunlight
      followed first-order kinetics. The impact of H2O2, humic acid, fulvic acid and
      acetone to enhance the photodegradation of sulfadiazine (SDZ) was studied. Six
      photoproducts, 4-OH-SDZ, 5-OH-SDZ, N-formyl-SDZ, 4-[2-iminopyrimidine-1(2H)-yl]
      aniline, 2-aminopyrimidine, and aniline were identified. Extrusion of SO2 was
      found to be the main degradation process during irradiation. These photoproducts
      can occur in water and soil upon sunlight exposure, when soil is treated with SDZ
      contained in manure. Due to photodegradation the experimental half-life of the
      SDZ in water was 32h and in the presence of photosensitizers the half-life values
      were 19.3-31.4h, 17.2-31.4h, 12.6-29.8h, and 3.8-30.7h for H2O2, humic acid,
      fulvic acid, and acetone, respectively depending on the concentration of the
      photosensitizers. The presence of photosensitizers markedly reduced SDZ
      persistence, indicating that indirect photolytic processes are important factors
      governing the photodegradation of SDZ in aqueous environments. Investigation
      revealed further persistence behavior of SDZ in manure. The half-life value of
      SDZ in manure was 158h.

PMID- 18076972
TI  - Dissolved and particulate metals (Fe, Zn, Cu, Cd, Pb) in two habitats from an
      active hydrothermal field on the EPR at 13 degrees N.
AB  - The distribution of Fe, Cu, Zn, Pb, Cd between the dissolved (<2 microm) and the
      particulate (>2 microm) fractions was measured after in-situ filtration in two
      hydrothermal habitats. The total metal concentration ranges exhibit a clear
      enrichment compared with the seawater concentration, accounting for the
      hydrothermal input for all the metals considered. Iron is the predominant metal
      (5-50 microM) followed by Zn and Cu. Cd and Pb are present at the nM level. At
      the scale studied, the behavior of temperature, pH and dissolved iron is semi
      conservative whereas the other dissolved and particulate metals are characterized
      by non-conservative patterns. The metal enrichment of the >2 microm fraction
      results from the settlement and accumulation of particulate matter close to the
      organisms, acting as a secondary metal source. The enrichment observed in the
      dissolved fraction can be related to the dissolution or oxidation of particles
      (mainly polymetallic sulfide) or to the presence of small particles and large
      colloids not retained on the 2 microm frit. SEM observations indicate that the
      bulk particulate observed is characteristic of crystalline particles settling
      rapidly from the high temperature smoker (sphalerite, wurtzite and pyrite),
      amorphous structures and eroded particles formed in the external zone of the
      chimney. Precipitation of Zn, Cu, Cd and Pb with Fe as wurtzite, sphalerite and
      pyrite is the main process taking place within the area studied and is semi
      quantitative. The distribution of the dominant observed fauna has been related to
      the gradient resulting from the dilution process, with the alvinellids worms
      colonizing the hotter and more variable part of the mixing zone, but also to the
      metallic load of the mixing zone. Dissolved and particulate metal concentrations
      are therefore necessary abiotic factors to be studied in a multiparametric
      approach to understand the faunal distribution in hydrothermal ecosystems.

PMID- 18076973
TI  - Arsenic re-mobilization in water treatment adsorbents under reducing conditions:
      Part II. XAS and modeling study.
AB  - The mechanism of arsenic re-mobilization in spent adsorbents under reducing
      conditions was studied using X-ray absorption spectroscopy and surface
      complexation model calculations. X-ray absorption near edge structure (XANES)
      spectroscopy demonstrated that As(V) was partially reduced to As(III) in spent
      granular ferric hydroxide (GFH), titanium dioxide (TiO2), activated alumina (AA)
      and modified activated alumina (MAA) adsorbents after 2 years of anaerobic
      incubation. As(V) was completely reduced to As(III) in spent granular ferric
      oxide (GFO) under 2-year incubation. The extended X-ray absorption fine structure
      (EXAFS) spectroscopy analysis showed that As(III) formed bidentate binuclear
      surface complexes on GFO as evidenced by an average As(III)-O bond distance of
      1.78 A and As(III)-Fe distance of 3.34 A. The release of As from the spent GFO
      and TiO2 was simulated using the charge distribution multi-site complexation (CD
      MUSIC) model. The observed redox ranges for As release and sulfate mobility were
      described by model calculations.

PMID- 18076974
TI  - Link between DOC in near surface peat and stream water in an upland catchment.
AB  - Hydrologic transport of dissolved organic carbon (DOC) from peat soils may differ
      to organo-mineral soils in how they responded to changes in flow, because of
      differences in soil profile and hydrology. In well-drained organo-mineral soils,
      low flow is through the lower mineral layer where DOC is absorbed and high flow
      is through the upper organic layer where DOC is produced. DOC concentrations in
      streams draining organo-mineral soils typically increase with flow. In saturated
      peat soils, both high and low flows are through an organic layer where DOC is
      produced. Therefore, DOC in stream water draining peat may not increase in
      response to changes in flow as there is no switch in flow path between a mineral
      and organic layer. To verify this, we conducted a high-resolution monitoring
      study of soil and stream water at an upland peat catchment in northern England.
      Our data showed a strong positive correlation between DOC concentrations at -1
      and -5 cm depth and stream water, and weaker correlations between concentrations
      at -20 to -50 cm depth and stream water. Although near surface organic material
      appears to be the key source of stream water DOC in both peat and organo-mineral
      soils, we observed a negative correlation between stream flow and DOC
      concentrations instead of a positive correlation as DOC released from organic
      layers during low and high flow was diluted by rainfall. The differences in DOC
      transport processes between peat and organo-mineral soils have different
      implications for our understanding of long-term changes in DOC exports. While
      increased rainfall may cause an increase in DOC flux from peat due to an increase
      in water volume, it may cause a decrease in concentrations. This response is
      contrary to expected changes in DOC exports from organo-mineral soils, where
      increase rainfall is likely to result in an increase in flux and concentration.

PMID- 18076975
TI  - A modelling approach to explore some hypotheses of the failure of neuroprotective
      trials in ischemic stroke patients.
AB  - Ischemic stroke is the third cause of death in industrialised countries, but no
      satisfactory treatment is currently available. The hundreds of neuroprotective
      drugs developed to block the ischemic cascade gave very promising results in
      animal models but the clinical trials performed with these drugs showed no
      beneficial effects in stroke patients. Many hypotheses were advanced to explain
      this discrepancy, among which the morphological and functional differences
      between human and rodent brains. This discrepancy could be partly due to the
      differences in white matter and glial cell proportions between human and rodent
      brains. In order to test this hypothesis, we built a mathematical model of the
      main early pathophysiological mechanisms of stroke in rodent and in human brains.
      This model is a two-scale model and relies on a set of ordinary differential
      equations. We built two versions of this model (for human and rodent brains)
      differing in their white matter and glial cell proportions. Then, we carried out
      in silico experiments with various neuroprotective drugs. The simulation results
      obtained with a sodium channel blocker show that the proportion of penumbra
      recovery is much higher in rodent than in human brain and the results are similar
      with some other neuroprotective drugs tested during phase III trials. This in
      silico investigation suggests that the proportions of glial cells and white
      matter have an influence on neuroprotective drug efficacy. It reinforces the
      hypothesis that histological and morphological differences between rodent and
      human brains can partly explain the failure of these agents in clinical trials.

PMID- 18076976
TI  - Regulation of conditioned and unconditioned fear in rats by 5-HT1A receptors in
      the dorsal periaqueductal gray.
AB  - Studies on the involvement of 5-HT1-mediated mechanisms in the dorsal
      periaqueductal gray (dPAG) of animals with past stressful experiences have not
      been conducted so far. We investigated the role of 5-HT1 receptors in the dPAG of
      rats previously submitted to contextual fear conditioning. Defensive behaviors
      induced by activation of the dPAG were assessed by measuring the lowest electric
      current applied to this structure (threshold) able to produce freezing and escape
      responses during testing sessions of contextual fear conditioning, in which
      animals were placed in a context previously paired to footshocks. The 5-HT1A
      function of the dPAG was evaluated by local injections of 8-OH-DPAT (4 and 8
      nmol/0.2 microL) and WAY-100635 (10 nmol/0.2 microL), selective agonist and
      antagonist of 5-HT1A receptors, respectively. In accordance with previous
      studies, 8-OH-DPAT increased aversive thresholds (antiaversive effects) but
      injections of WAY 100635 into the dPAG did not produce significant effects on the
      aversive thresholds in naive rats. However, the aversive thresholds of animals
      exhibiting contextual fear remained unchanged with both treatments. Moreover, 8
      OH-DPAT and WAY 100635 did not change the dPAG post-stimulation freezing. The
      present results suggest that the stressful experience of being fear conditioned
      has an effect on the role of the 5-HT1A receptors in mediating unconditioned
      fear. Also, the reduction in the regulation of the defensive behaviors by 5-HT1A
      mediated mechanisms in the dPAG of these animals may underlie the stress
      precipitated psychopathology associated with the neural substrates of aversion of
      the dPAG.

PMID- 18076977
TI  - Synchronization of follicular wave emergence prior to superovulation in Bactrian
      camel (Camelus bactrianus).
AB  - This study was conducted to synchronize follicle wave emergence prior to
      superovulation using either GnRH or progestogen treatments, in Bactrian camels.
      GnRH group camels (n=5) received 20 microg of the GnRH analogue Buserelin on Days
      -18 and -4 of the experiment (initiation of superovulation=Day 0). Camels in the
      progestogen group (n=5) received two consecutive treatments of progestogens, 7
      days apart, on Days -14 and -8 of the experiment. On each occasion, each female
      received three norgestomet implants and 200mg progesterone (i.m.) and all
      implants were removed 14 days after the first progestogen treatment coinciding
      with Day -1 of superovulation. A combination of eCG and FSH was used to induce
      superovulation and the growth of all subsequent follicles and CLs were monitored
      daily by ultrasonography. Following the first GnRH injection, mature follicles
      ovulated within 1-2 days, and a new follicle wave emerged after 3+/-0.77 days. At
      the time of the second GnRH injection, a mature follicle (15.6+/-0.97 mm)
      ovulated and a new follicular wave emerged between 1 and 2 days after GnRH
      injection. Growing follicles at the time of the first progestogen treatment
      became either atretic (n=1) or persistent (n=4) and a new follicle wave (n=3)
      emerged 3-6 days later. At the initiation of superovulation, the diameters of the
      largest follicle in GnRH and progestogen groups were 7.4+/-0.59 and 20.5+/-2.26
      mm, respectively but after superovulation and mating there was no significant
      differences in the number of unovulated follicles or CLs between groups. In
      conclusion, two GnRH injections, 14 days apart, may be used to synchronize
      follicle wave emergence in Bactrian camel.

PMID- 18076978
TI  - The production of Turkish relative clauses in agrammatism: Verb inflection and
      constituent order.
AB  - This study presents results from a sentence completion test that examines the
      production of finite main clauses and non-finite relative clauses in Turkish
      agrammatic speech. In main clauses, the verb is finite and all its constituents
      are in their base positions. In relative clauses, the verb is a participle and
      the NP undergoes overt movement to an A-bar position. The results show that non
      finite relative clauses with overt movement as such are more difficult to produce
      than finite main clauses with a base order. The findings are discussed with
      respect to several hypotheses on finite verbs and syntactic complexity. The
      conclusion is that Turkish agrammatic speakers have more problems in producing
      structurally derived clauses and the production of verbs is influenced by
      linguistic factors such as the overt movement of the NP.

PMID- 18076979
TI  - Holiday and school-term sleep patterns of Australian adolescents.
AB  - The holiday and school-term sleep patterns of 310 Australian senior school
      students were surveyed in a longitudinal study, along with self-reported sleep
      quality, mood, daytime functioning, grades and circadian preference. Evidence was
      found that with the impact of school schedule, students accrued a significant
      sleep debt, obtaining insufficient sleep for their needs and reporting lowered
      mood and daytime functioning. Support was found for the hypothesis that trait
      circadian preference mediates mood, daytime functioning and academic grades
      through its effect on sleep variables at school time. It was concluded that while
      the imposition of school schedule negatively impacted on mood and daytime
      functioning for the sample as a whole, evening-oriented adolescents were the most
      vulnerable to poorer outcomes. These students obtained poorer quality and less
      sleep than morning-oriented students. Sleep factors impacted negatively on
      evening-oriented students' mood and ability to function at school during the day,
      which in turn predicted poorer academic achievement.

PMID- 18076980
TI  - Retrospective report of social withdrawal during adolescence and current
      maladjustment in young adulthood: cross-cultural comparisons between Australian
      and South Korean students.
AB  - The current study investigated associations between the frequency of and
      motivations for social withdrawal during adolescence and emotional distress in
      young adulthood. Perceived motivations for social withdrawal included
      unsociability, isolation, shyness, and low mood. Social withdrawal during
      adolescence was assessed using a retrospective questionnaire completed by
      Australian and Korean university students. They also completed measures of
      general self-worth, social relationships, loneliness, social anxiety, and
      depression at university. Partial correlations and path analyses revealed that
      different motivations for social withdrawal had different risk status for later
      adjustment across the two samples. In particular, it appeared that shy and
      unsociable individuals in Korea showed better social and emotional adjustment
      than their counterparts in Australia. In contrast, social relationships of
      sad/depressed and isolated respondents in Korea appeared to be more seriously
      impaired than their Australian counterparts. These cross-cultural differences are
      discussed in terms of socio-cultural values and environments unique to the two
      countries.

PMID- 18076981
TI  - Countervailing social network influences on problem behaviors among homeless
      youth.
AB  - The impact of countervailing social network influences (i.e., pro-social, anti
      social or HIV risk peers) on problem behaviors (i.e., HIV drug risk, HIV sex risk
      or anti-social behaviors) among 696 homeless youth was assessed using structural
      equation modeling. Results revealed that older youth were less likely to report
      having pro-social peers and were more likely to have HIV risk and anti-social
      peers. A longer time homeless predicted fewer pro-social peers, more anti-social
      peers, and more HIV risk peers. Heterosexual youth reported fewer HIV risk peers
      and more pro-social peers. Youth recruited at agencies were more likely to report
      pro-social peers. Having pro-social peers predicted less HIV sex risk behavior
      and less anti-social behavior. Having HIV risk peers predicted all problem
      behavior outcomes. Anti-social peers predicted more anti-social behavior. Once
      the association between anti-social and HIV risk peers was accounted for
      independently, having anti-social peers did not independently predict sex or drug
      risk behaviors.

PMID- 18076982
TI  - Production of chitinolytic enzymes by a strain (BM17) of Paenibacillus pabuli
      isolated from crab shells samples collected in the east sector of central
      Tyrrhenian Sea.
AB  - Nineteen bacterial isolates were grown in shaken cultures in media containing
      chitin as carbon source and different additional nitrogen sources such as yeast
      nitrogen base (YNB), yeast extract (YE), corn steep liquor (CSL) and ammonium
      sulfate. Strain BM17 showed the highest activity (200 U/l) in medium containing
      Chitin (1%) and YNB (0.5%). Molecular analysis of the 16S rRNA gene showed that
      strain BM17 belongs to the species Paenibacillus pabuli (99.72% homology). The
      enzyme activity started after 12-24 h; exponential enzyme production was recorded
      from the 24th h and lasted till the 96th h of incubation when activity peaked to
      decrease thereafter. Medium optimisation was carried out by Response Surface
      Methodology (RSM) considering the effects of chitin, corn steep liquor and yeast
      extract. BM17 chitinolytic activity was induced by chitin but the increase of its
      concentration did not have significant effects on the enzyme activity. By
      contrast, the nitrogen source, particularly YE, strongly affected the enzyme
      production.

PMID- 18076983
TI  - Recombinant human collagen for tissue engineered corneal substitutes.
AB  - We successfully fabricated transparent, robust hydrogels as corneal substitutes
      from concentrated recombinant human type I and type III collagen solutions
      crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N
      hydroxysuccinimide (NHS). White light transmission through these gels is
      comparable or superior to that of human corneas. Hydrogels from both type I and
      type III collagens supported in vitro epithelium and nerve over-growth. While
      both these biocompatible hydrogels have adequate tensile strength and elasticity
      for surgical manipulation, type III collagen hydrogels tended to be mechanically
      superior. Twelve-month post-implantation results of type I recombinant collagen
      based corneal substitutes into mini-pigs showed retention of optical clarity,
      along with regeneration of corneal cells, nerves and tear film. For clinical use,
      implants based on fully characterized, recombinant human collagen eliminate the
      risk of pathogen transfer or xenogeneic immuno-responses posed by animal
      collagens.

PMID- 18076985
TI  - Generation of highly potent nonviral gene vectors by complexation of lipoplexes
      and transferrin-bearing fusogenic polymer-modified liposomes in aqueous glucose
      solution.
AB  - We reported previously that complexation of lipoplexes containing 3,5
      dipentadecyloxybenzamidine (TRX-20) and transferrin-bearing succinylated
      poly(glycidol) (SucPG)-modified liposome, which becomes fusogenic under weakly
      acidic conditions, might produce gene carriers with high transfection activity.
      For the present study, we prepared the lipoplex-SucPG-modified liposome complexes
      by mixing them either in phosphate-buffered saline or in an aqueous 5% glucose
      solution. The complexes prepared in phosphate-buffered saline have large
      particles of more than 800 nm, whereas the complexes prepared in the glucose
      solution were remarkably small: 200-300 nm. The small complexes were taken up
      more effectively by HeLa cells, and their transfection was induced more
      efficiently than the large complexes'. In addition, the small complexes achieved
      cellular transfection more efficiently in the presence of serum than in the
      absence of serum, without marked cytotoxicity. Considering that their affinity to
      the cell is based on ligand-receptor interaction, the small complexes are highly
      promising as a safe vector with high transfection activity and high target cell
      specificity.

PMID- 18076984
TI  - Tissue engineering intrafusal fibers: dose- and time-dependent differentiation of
      nuclear bag fibers in a defined in vitro system using neuregulin 1-beta-1.
AB  - While much is known about muscle spindle structure, innervation and function,
      relatively few factors have been identified that regulate intrafusal fiber
      differentiation and spindle development. Identification of these factors will be
      a crucial step in tissue engineering functional muscle systems. In this study, we
      investigated the role of the growth factor, neuregulin 1-beta-1 (Nrg 1-beta-1)
      EGF, for its ability to influence myotube fate specification in a defined culture
      system utilizing the non-biological substrate N-1[3-(trimethoxysilyl)propyl]
      diethylenetriamine (DETA). Based on morphological and immunocytochemical
      criteria, Nrg 1-beta-1 treatment of developing myotubes increases the ratio of
      nuclear bag fibers to total myotubes from 0.019 to 0.100, approximately a five
      fold increase. The myotube cultures were evaluated for expression of the
      intrafusal fiber-specific alpha cardiac-like myosin heavy chain and for the
      expression of the non-specific slow myosin heavy chain. Additionally, the
      expression of ErbB2 receptors on all myotubes was observed, while phosphorylated
      ErbB2 receptors were only observed in Nrg 1-beta-1-treated intrafusal fibers.
      After Nrg 1-beta-1 treatment, we were able to observe the expression of the
      intrafusal fiber-specific transcription factor Egr3 only in fibers exhibiting the
      nuclear bag phenotype. Finally, nuclear bag fibers were characterized
      electrophysiologically for the first time in vitro. This data shows conclusively,
      in a serum-free system, that Nrg 1-beta-1 is necessary to drive specification of
      forming myotubes to the nuclear bag phenotype.

PMID- 18076987
TI  - Protein release kinetics for core-shell hybrid nanoparticles based on the layer
      by-layer assembly of alginate and chitosan on liposomes.
AB  - The present work is focused on the formulation of core-shell nanoparticles via
      the layer-by-layer (L-b-L) self-assembly technique for delivery of
      biomacromolecules such as bone growth factors. The drug encapsulation efficiency
      of liposomes is enhanced with the increased stability of polyelectrolyte systems
      achieved through the alternate adsorption of several layers of natural polymers:
      anionic alginate and cationic chitosan on cationic nanosized phospholipid
      vesicles. The resulting particles were characterized for their size, surface
      charge, morphology, encapsulation efficiency, loading capacity and release
      kinetics over an extended period of 30 days. The L-b-L deposition technique
      succeeded in building a spherical, monodisperse and stable hybrid nanoparticulate
      protein delivery system with a cumulative size of 383+/-11.5 nm and zeta
      potential surface charge of 44.61+/-3.31 mV for five bilayered liposomes. The
      system offers numerous compartments for encapsulation including the aqueous core
      and within the polyelectrolyte shell demonstrating good entrapment and sustained
      linear release of a model protein, bovine serum albumin, in vitro. Our results
      demonstrate that this delivery system features an extended shelf life and can be
      loaded immediately prior to administration, thus preventing any loss of the
      protein.

PMID- 18076986
TI  - The incorporation of poly(lactic-co-glycolic) acid nanoparticles into porcine
      small intestinal submucosa biomaterials.
AB  - Small intestinal submucosa (SIS) derived from porcine small intestine has been
      intensively studied for its capacity in repairing and regenerating wounded and
      dysfunctional tissues. However, SIS suffers from a large spectrum of
      heterogeneity in microarchitecture leading to inconsistent results. In this
      study, we introduced nanoparticles (NPs) to SIS with an intention of decreasing
      the heterogeneity and improving the consistency of this biomaterial. As
      determined by scanning electron microscopy and urea permeability, the optimum NP
      size was estimated to be between 200 nm and 500 nm using commercial monodisperse
      latex spheres. The concentration of NPs that is required to alter pore sizes of
      SIS as determined by urea permeability was estimated to be 1 mg/ml 260 nm
      poly(lactic-co-glycolic) acid (PLGA) NPs. The 1mg/ml PLGA NPs loaded in the SIS
      did not change the tensile properties of the unmodified SIS or even alter pH
      values in a cell culture environment. More importantly, PLGA NP modified SIS did
      not affect human mammary endothelial cells (HMEC-1) morphology or adhesion, but
      actually enhanced HEMC-1 cell growth.

PMID- 18076988
TI  - Induction of trophoblast cell fusion by a protein tyrosine phosphatase inhibitor.
AB  - In the placenta, trophoblast cell fusion leads to the formation of the
      syncytiotrophoblast, which plays an essential role in the diffusion of nutrients
      and hormones from the mother to the fetus. Different protein tyrosine kinases are
      involved in the modulation of this biological process. Herein, we investigated
      the impact of a protein tyrosine phosphatase (PTP) inhibitor (bpV[pic]) on
      trophoblast fusion. Upon bpV[pic] or forskolin treatment, primary and BeWo
      trophoblastic cells demonstrated higher cAMP levels and a more potent induction
      of cell fusion, while non-fusogenic JEG-3 cells were non-responsive to these
      treatments. RT-PCR analyses on stimulated BeWo cells or primary cytotrophoblast
      cells demonstrated an increase in syncytin-1 mRNA levels, which was more
      pronounced upon forskolin/bpV[pic] treatment. Using the luciferase gene upstream
      of the syncytin-1 promoter, similar results were obtained in BeWo cells after
      stimulation. These results demonstrate that PTPs act negatively on cell fusion in
      human trophoblasts and could control the timing of syncytiotrophoblast formation
      during placenta development.

PMID- 18076989
TI  - Immunotoxic effects on freshwater mussels of a primary-treated wastewater before
      and after ozonation: a pilot plant study.
AB  - The immunotoxic potential of a primary-treated municipal effluent following
      enhanced disinfection by ozonation was studied in the freshwater mussel Elliptio
      complanata. Mussels were exposed to increasing concentrations (0%, 1%, 3%, 10%,
      and 20% v/v) of the effluent before and after ozone treatment (approximately 10
      mg/L of purged O(3)) in a continuous flow-through laboratory for 7 weeks.
      Immunocompetence was appraised by measuring phagocytosis, cell viability
      (fluorescein retention), cell adherence to polystyrene micro-wells,
      cyclooxygenase (COX) activity and total nitrite levels in peripheral hemocytes
      from the hemolymphs. The results showed that phagocytosis was significantly
      inhibited by the primary-treated effluent at a threshold concentration of 1.7%
      v/v. Cell viability was also significantly reduced three-fold compared to
      controls at the same effluent threshold concentration, but hemocyte adherence was
      unchanged. COX activity was increased 1.3-fold at a threshold concentration of
      14% v/v. Total nitrite levels were significantly increased 2.2-fold at a
      threshold concentration of 5.5% v/v. Ozone treatment of the effluent was not
      successful in removing phagocytic inhibition, but did completely remove
      cytotoxicity from hemocytes. Ozonation also reduced cell adherence at a threshold
      concentration of 1.7% v/v. The inflammatory properties of the effluent appeared
      to be accentuated by the ozone, as evidenced by an increase in COX activity,
      which reached 2.6-fold activity compared to controls, as compared to the 1.3-fold
      increase witnessed in the primary-treated effluent. Furthermore, total nitrite
      levels reached a two-fold induction at a threshold concentration of 1.7% v/v in
      the ozone-enhanced effluent compared to 5.5% v/v in the primary-treated effluent.
      In conclusion, ozonation of a primary-treated effluent successfully reduced
      microbial loading and completely removed cytotoxicity, but increased the
      inflammatory properties of the effluent. Investigations aimed at examining the
      impacts of sustained inflammation on the host's capacity to remove potentially
      pathogenic bacteria are recommended.

PMID- 18076990
TI  - Biomarker responses in wild three-spined stickleback (Gasterosteus aculeatus L.)
      as a useful tool for freshwater biomonitoring: a multiparametric approach.
AB  - The biochemical response of wild sticklebacks collected in Autumn 2005 at seven
      stations in the North of France was studied using a set of complementary
      biomarkers. Here, data on biotransformation of xenobiotics, oxidative stress
      exposure and damages, neurotoxicity and endocrine disruption are provided. All
      the sites are characterized by a specific response pattern that allows
      distinguishing sampling locations. Moreover, these responses are in accordance
      with data on existing environmental pressures and the chemical analysis of metals
      performed in surface water. The assessment of individual responses is completed
      by fish population disturbance monitoring. Based on these measurements, the
      investigated sites are characterized by different levels of disturbance. This
      study argues for a multi-parametric approach of aquatic ecosystem contamination
      based on association between chemical, biochemical and ecological endpoints and
      provides a testimony of the usefulness of stickleback for this purpose.

PMID- 18076991
TI  - The consequence of premature silicone stent loss after external
      dacryocystorhinostomy.
AB  - PURPOSE: To investigate the clinical affects of premature silicone stent loss
      after external dacryocystorhinostomy (DCR). DESIGN: Retrospective chart review.
      PARTICIPANTS: Two hundred thirty-three consecutive external
      dacryocystorhinostomies. METHODS: Demographic information was recorded, including
      length to follow-up, age, gender, number of days until stent removal, and success
      of surgery. All patients who extruded their silicone stent prematurely were
      identified. All were primary DCRs (i.e., all reoperations were excluded). All
      patients had had documented nasolacrimal duct obstruction before surgery, with or
      without current or prior dacryocystitis. MAIN OUTCOMES MEASURES: Failure of DCR
      surgery was accepted as symptomatic epiphora with notable nasolacrimal duct
      blockage and/or infection at long term follow-up. RESULTS: Of the 233 DCRs, 42
      stents extruded or had to be removed before the planned 2-month period. The
      overall success rate of the surgery was 94.9%, with a 90.5% success for those who
      had early extrusion and 95.8% for those who did not (P = 0.24). Moreover, of the
      4 people who had a failed surgery (of 42 early extrusions), none had a recurrent
      infection or pain, and only 1 opted to have a revision of the surgery. Patient
      age, gender, or timing of the extrusion was not found to affect surgical success
      significantly. CONCLUSIONS: Our experience and this study suggest that concerns
      over early stent extrusion or removal may not be wholly warranted. Moreover, our
      review of the literature shows no evidence-based recommendations that longer
      stent retention or reintubation after early extrusion results in a higher success
      rate. Although other surgeries (e.g., canalicular laceration, congenital
      epiphora) may benefit from intervention or reinsertion after early extrusion, we
      cannot extrapolate such a practice for the DCR.

PMID- 18076992
TI  - Glaucoma is associated with peripheral vascular endothelial dysfunction.
AB  - PURPOSE: To evaluate peripheral vascular endothelial function in patients with
      normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG) using
      noninvasive endothelium-dependent flow-mediated vasodilation (FMD). DESIGN: Case
      control study. PARTICIPANTS: Thirty patients with NTG, 30 with POAG, and 30
      healthy age- and gender-matched controls. METHODS: Participants underwent
      measurement of FMD and endothelium-independent nitroglycerin-mediated
      vasodilation (NMD) via high-resolution 2-dimensional ultrasonographic imaging of
      the brachial artery. All patients also underwent blood sampling for biochemistry,
      lipid profile, and high sensitivity C-reactive protein analysis. MAIN OUTCOME
      MEASURES: The association of FMD with NTG and POAG. RESULTS: The FMD values
      differed significantly between the patients with NTG, those with POAG, and
      controls: NTG, 2.70+/-2.25%; POAG, 5.33+/-2.81%; controls, 7.21+/-2.36%; P<0.001.
      In comparison with the POAG group and normal controls, the NTG group demonstrated
      markedly impaired FMD. The POAG group exhibited higher intermediate FMD than the
      NTG group (P<0.001) but significantly lower FMD than normal controls (P = 0.012).
      Multivariate analysis indicated that independent predictors for impaired FMD were
      presence of NTG, presence of POAG, and advanced age. Additionally, FMD values
      were significantly lower in glaucoma patients than in controls (4.02+/-2.85% vs.
      7.21+/-2.36%; P<0.001). CONCLUSIONS: Patients with glaucoma have impaired FMD.
      Additionally, patients with NTG have lower FMD than those with POAG.

PMID- 18076993
TI  - Dengue virus infection induces passive release of high mobility group box 1
      protein by epithelial cells.
AB  - OBJECTIVES: Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are
      severe complications of secondary dengue virus (DV) infection. In the current
      study, we provide the first evidence of induction of cellular necrosis by DV type
      2 (DV-2). METHODS AND RESULTS: The epithelial cell line A549 can support
      replication of dengue virus as demonstrated by expression of viral NS1 antigen
      and virus plaque assay. DV-2 infection of cells induced cell death in
      approximately half of the cells that were actively infected. Using sodium 3'-[1
      (phenylaminocarbonyl)-3, 4-tetrazolium]-bis(4-methoxy-6-nitro) benzene sulfonic
      acid hydrate [XTT]-based cell viability assays, we found that DV-2 infection at a
      multiplicity of infection (MOI) of 10 resulted in significant death of cells as
      well as high extracellular lactate dehydrogenase (LDH) activity and leakage of
      the high mobility group 1 (HMGB1) protein into the extracellular space.
      CONCLUSIONS: These results suggest that HMGB1 may be a signal of tissue or
      cellular injury by DV-2, which in turn is likely to induce and/or enhance an
      immune reaction.

PMID- 18076994
TI  - Role of receptor internalization in opioid tolerance and dependence.
AB  - Agonist-induced mu-opioid receptor (MOPr) internalization has long been suggested
      to contribute directly to functional receptor desensitization and opioid
      tolerance. In contrast, recent evidence suggests that opioid receptor
      internalization could in fact reduce opioid tolerance in vivo, but the mechanisms
      that are responsible for the internalization-mediated protection against opioid
      tolerance are controversely discussed. One prevailing hypothesis is, that
      receptor internalization leads to decreased receptor signaling and therefore to
      reduced associated compensatory changes in downstream signaling systems that are
      involved in the development of opioid tolerance. However, numerous studies have
      demonstrated that desensitized and internalized mu-opioid receptors are rapidly
      recycled to the cell surface in a reactivated state, thus counteracting receptor
      desensitization and opioid tolerance. Further studies revealed agonist-selective
      differences in the ability to induce opioid receptor internalization. Recently it
      has been demonstrated that the endocytotic efficacies of opioids are negatively
      correlated to the induced opioid tolerance. Thus, clearer understanding of the
      role of opioid receptor trafficking in the regulation of opioid tolerance and
      dependence will help in the treatment of patients suffering from chronic pain or
      drug dependence.

PMID- 18076995
TI  - Predictors of amygdala activation during the processing of emotional stimuli: a
      meta-analysis of 385 PET and fMRI studies.
AB  - Although amygdala activity has been purported to be modulated by affective and
      non-affective factors, considerable controversy remains on its precise functional
      nature. We conducted a meta-analysis of 385 functional neuroimaging studies of
      emotional processing, examining the effects of experimental characteristics on
      the probability of detecting amygdala activity. All emotional stimuli were
      associated with higher probability of amygdala activity than neutral stimuli.
      Comparable effects were observed for most negative and positive emotions, however
      there was a higher probability of activation for fear and disgust relative to
      happiness. The level of attentional processing affected amygdala activity, as
      passive processing was associated with a higher probability of activation than
      active task instructions. Gustatory-olfactory and visual stimulus modalities
      increased the probability of activation relative to internal stimuli. Aversive
      learning increased the probability of amygdala activation as well. There was some
      evidence of hemispheric specialization with a relative left-lateralization for
      stimuli containing language and a relative right-lateralization for masked
      stimuli. Methodological variables, such as type of analysis and magnet strength,
      were also independent predictors of amygdala activation.

PMID- 18076996
TI  - A micro-batchwise technique method for rapid reconstitution of functionally
      active mitochondrial ADP/ATP carrier from Jerusalem artichoke (Helianthus
      tuberosus L.) tubers.
AB  - A method for rapid reconstitution of ADP/ATP carrier from Jerusalem artichoke
      (Helianthus tuberosus L.) tubers mitochondria in proteoliposomes is described.
      The method is based on the well known property of the Amberlite resin to absorb
      the detergent allowing proteoliposome formation. This has been achieved by a
      micro-batchwise technique, using a rotating plate stirrer. An evaluation of the
      optimal conditions, in comparison with the more usual column method is presented.
      The purified ADP/ATP carrier, incorporated in proteoliposomes by this method,
      shows a high transport activity and a higher specific activity with respect to
      proteoliposomes obtained by the column procedure. Furthermore the proteoliposomal
      preparations are more homogeneous in size, with a diameter ranging from 300 to
      350 nm. The method is suitable for the reconstitution of other membrane transport
      proteins.

PMID- 18076997
TI  - A scriptable DSP-based system for dynamic conductance injection.
AB  - A variety of software and hardware systems have been developed to inject
      controlled electrical conductances into excitable cells, to investigate the
      physiological mechanisms of action potential generation. These systems face
      several challenges: the need to model complex conductances, including voltage
      gated ion channels, synaptic conductances controlled by electrical models of
      entire cells or even networks of cells, to do so rapidly and stably, with
      precisely controlled update intervals of 20micros or less, and to present an easy
      and flexible interface to the user, allowing new experiments to be designed and
      executed easily. In this paper I describe a new software system (SM-2) which is
      designed to meet these requirements, and which runs on the current generation of
      digital-signal-processing (DSP) analog input-output I/O boards, hosted in Windows
      PCs. Its key innovation is its configurability by simple user-written text
      scripts, or "scriptability", which gives it a high flexibility of purpose, and
      allows non-programmers the capacity to rapidly design and use new Hodgkin-Huxley
      type active conductances, conductances with arbitrary current-voltage
      relationships, Markov process conductance mechanisms with user-specified rate
      matrices, and hybrid networks of virtual cells. At the same time, the hardware
      platform allows this to be achieved with a fast and accurately timed input
      computation-output cycle.

PMID- 18076998
TI  - An investigation of cerebral edema and injury volume assessments for controlled
      cortical impact injury.
AB  - Using the controlled cortical impact (CCI) model, our laboratory compared edema
      in contralateral and ipsilateral regions to help clarify conflicting reports of
      contralateral edema and for enhanced assessment and interpretation of CCI injury
      pathophysiology. This investigation examined regional edema in response to graded
      injury severities over time with regards to tissue damage. Prior to injury rats
      were anesthetized with ketamine and xylazine (1:1). CCI injury parameters were
      set at 4.0m/s and 120 to 130 ms. Rats were randomized to receive moderate or
      severe injuries set at 2.0 and 3.0mm depths, respectively. Cerebral edema and
      injury volume were examined separately following euthanasia with pentobarbital.
      Cerebral edema was measured using the wet-dry weight technique at 24 or 48 h
      after injury. Sham animals underwent all surgical procedures except the impact
      injury. Injury volume was quantified using 2,3,5-triphenyltetrazolium chloride
      staining at 24h or 7 days after injury. The results of this investigation confirm
      that cerebral edema is absent in the uninjured, contralateral hemisphere after
      moderate and severe CCI injury. There were regional differences in cerebral edema
      formation in the hemisphere ipsilateral to injury that were dependent on injury
      severity and the length of time after injury. Tissue damage was reduced over 7
      days following moderate CCI injury. CONCLUSIONS: (1) the absence of edema in the
      contralateral hemisphere allows it to serve as a valid control for edema
      formation, (2) misrepresenting injury volume because of edema continues to be a
      problem for evaluating CCI injury and treatment efficacy, and (3) reduced injury
      volume over 7 days following CCI injury suggests tissue recovery after initial
      dysfunction.

PMID- 18076999
TI  - Effects of imperfect dynamic clamp: computational and experimental results.
AB  - In the dynamic clamp technique, a typically nonlinear feedback system delivers
      electrical current to an excitable cell that represents the actions of "virtual"
      ion channels (e.g., channels that are gated by local membrane potential or by
      electrical activity in neighboring biological or virtual neurons). Since the
      conception of this technique, there have been a number of different
      implementations of dynamic clamp systems, each with differing levels of
      flexibility and performance. Embedded hardware-based systems typically offer
      feedback that is very fast and precisely timed, but these systems are often
      expensive and sometimes inflexible. PC-based systems, on the other hand, allow
      the user to write software that defines an arbitrarily complex feedback system,
      but real-time performance in PC-based systems can be deteriorated by imperfect
      real-time performance. Here, we systematically evaluate the performance
      requirements for artificial dynamic clamp knock-in of transient sodium and
      delayed rectifier potassium conductances. Specifically, we examine the effects of
      controller time step duration, differential equation integration method, jitter
      (variability in time step), and latency (the time lag from reading inputs to
      updating outputs). Each of these control system flaws is artificially introduced
      in both simulated and real dynamic clamp experiments. We demonstrate that each of
      these errors affect dynamic clamp accuracy in a way that depends on the time
      constants and stiffness of the differential equations being solved. In
      simulations, time steps above 0.2ms lead to catastrophic alteration of spike
      shape, but the frequency-current relationship is much more robust. Latency (the
      part of the time step that occurs between measuring membrane potential and
      injecting re-calculated membrane current) is a crucial factor as well.
      Experimental data are substantially more sensitive to inaccuracies than simulated
      data.

PMID- 18077000
TI  - Dissociative experiences differentiate bipolar-II from unipolar depressed
      patients: the mediating role of cyclothymia and the Type A behaviour speed and
      impatience subscale.
AB  - BACKGROUND: Dissociative symptoms are often seen in patients with mood disorders,
      but there is little information on possible association with subgroups and
      temperamental features of these disorders. METHODS: The Dissociative Experience
      Scale was administered to 85 patients with a DSM-IV Major Depressive Disorder
      (MDD) or Bipolar-II Disorder (BP-II). Both broad-spectrum dissociation (DES total
      score) and clearly pathological forms of dissociation (DES-Taxon) were assessed.
      Temperament was assessed using Akiskal and Mallya;s criteria of Affective
      Temperaments and the Jenkins Activity Survey (JAS) for Type A Behaviour. RESULTS:
      Sixty-five patients gave valid answers to DES. The mean DES and DES-T scores were
      higher in BP-II (16.8 and 12.7 respectively) compared to MDD (9.0 and 5.7); DES
      odds ratio (OR)=1.58 (95% CI 1.15-2.18) and DES-T OR=1.60 (95% CI 1.14-2.25)
      using univariate logistic regression analyses. There was no significant
      difference in DES score in patients with (n=30) and without an affective
      temperament (n=35): mean (95% CI), 13.5 vs. 10.5 (-7.8 to 1.9), p=0.224. However
      the subgroup with a cyclothymic temperament (n=18) had higher DES scores (mean
      (95% CI): 17.8 vs. 9.7 (2.9-13.3), p=0.003), compared to patients without such a
      temperament. There was no significant difference in DES scores for patients with
      (n=35) or without (n=28) a Type A behaviour pattern (JAS>0): mean (95% CI) 12. 7
      vs. 10.9 (-6.8 to 3.3), p=0.491), but a positive JAS factor S score (speed and
      impatience subscale) was associated with significantly higher DES scores than a
      negative S-score: mean (95% CI) 14.9 vs. 9.0 (1.1-10.7), p=0.017), and this was
      still significant (p=0.005) using multiple linear regression of DES scores vs.
      the JAS subscale scores. DES-T scores were significantly higher in patients with
      OCD (n=9) (mean (95% CI) 18.4 vs. 6.6 (6.0-17.7), p<0.001); eating disorder
      (n=13) (14.0 vs. 6.8 (1.8-12.6), p=0.009), psychotic symptoms during depressions
      (n=9) (16.6 vs. 6.9 (3.7-15.8), p=0.002), and in those with a history of suicide
      attempt (n=28) (11.9 vs. 5.4 (2.2-10.8), p=0.003), but only OCD was an
      independent predictor after multiple linear regression of DES-T scores vs. all co
      morbid disorders (p=0.043). LIMITATIONS: The major limitation of the present
      study is a non-blind evaluation of affective diagnosis and temperaments, and
      assessment in a non-remission clinical status. CONCLUSIONS: Dissociative symptoms
      measured with the Dissociative Experience Scale are associated with bipolar
      features, using formal DSM-IV criteria, cyclothymic temperament and the speed and
      impatience subscale of the JAS.

PMID- 18077001
TI  - Construction and functional test of a chicken MHC-I (BF2*15)/peptide tetramer.
AB  - The major histocompatibility complex class I (MHC class I) peptide tetramer is a
      sensitive and valuable tool to evaluate antigen-specific cytotoxic T lymphocytes
      (CTLs) of many animal species. To date, no chicken MHC class I peptide tetramer
      has been reported. In this report, we describe construction and functional
      evaluation of a chicken MHC-I (BF2*15)/peptide tetramer. To construct the chicken
      MHC class I peptide tetramer, genes of the chicken MHC-I alpha chain (BF2*15) and
      beta2 microglobulin (Chbeta2m) were synthesized by RT-PCR from the total RNA of
      PBMCs and the signal sequences were deleted. The BF2*15 was then fused with the
      BirA substrate peptide (BSP) sequence at the C terminus. Next, the synthesized
      PCR products of BF2*15 and Chbeta2m were cloned into the expression vector pET
      28a (+) and expressed in Escherichia coli strain BL21 (DE3). Highly purified
      BF2*15-BSP heavy chain and Chbeta2m were obtained by a Ni(2+) NTA column affinity
      purification, yielding approximately 1.6mg of BF2*15-BSP and 2.4mg of Chbeta2m
      per 1g of the pelleted bacteria. The purified BF2*15-BSP heavy chain and Chbeta2m
      were refolded with synthetic peptide originated from infectious bronchitis virus
      nucleoprotein (IBV N(71-78)) in refolding buffer to generate the monomer of
      BF2*15/peptide complex. The monomer was then biotinylated and tetramerized using
      PE-labeled streptavidin. Upon functional evaluation of the construct by using
      flowcytometry, we observed that 3.65% of CTLs were specific to IBV nucleoprotein.
      This demonstrates that the CTL response of IBV-infected chicks could effectively
      be evaluated using the prepared MHC-I BF2*15/peptide tetramer.

PMID- 18077002
TI  - IdeE reduces the bactericidal activity of equine neutrophils for Streptococcus
      equi.
AB  - Streptococcus equi (S. equi) causes equine strangles, a highly contagious and
      widespread purulent lymphadenitis of the head and neck. Highly resistant to
      phagocytosis, it produces long extracellular chains in affected lymph nodes. In a
      screen of clones reactive with convalescent serum from a gene library of S. equi
      CF32 we identified IdeE, an IgG-endopeptidase and homologue of the leucocyte
      receptor Mac-1 (CD11b). IdeE is expressed during S. equi infection eliciting both
      serum and mucosal antibody responses which persisted at significant levels in
      serum for over 200 days. Release from S. equi into culture medium was detected
      during the exponential phase of growth. The closely related Streptococcus
      zooepidemicus appeared to store the protein but not to release it. Antiphagocytic
      activity for equine neutrophils was dose-dependent and neutralized by IdeE
      specific antiserum. Biotinylated IdeE bound weakly to about 77% of purified
      equine neutrophils and strongly to the remainder.

PMID- 18077003
TI  - Immunostimulatory effects of fucoidan on bone marrow-derived dendritic cells.
AB  - Fucoidan is a polysaccharide purified from the brown seaweed Fucus vesiculosus.
      Although some effects of fucoidan on immune functions have been elucidated, there
      have been no studies concerning the immunomodulatory effects of fucoidan on
      dendritic cells (DCs), which are powerful antigen-presenting cells. In this
      study, fucoidan increased the viability of DCs, the production of interleukin-12
      and tumor necrosis factor-alpha, and the expression of major histocompatibility
      complex class I, class II, CD54, and CD86 molecules. Furthermore, fucoidan
      treated DCs showed decreased antigen uptake and increased proliferation of
      allogeneic splenocytes. In a study of the transcriptional regulation effects of
      fucoidan, translocation of p65 molecules of nuclear factor-kappaB (NF-kappaB)
      from the cytosol to the nucleus was clearly observed in fucoidan-treated DCs.
      Taken together, the results suggest that fucoidan has immunostimulating and
      maturing effects on DCs, via a pathway involving at least NF-kappaB.

PMID- 18077004
TI  - Neuronal nicotinic alpha7 receptors modulate inflammatory cytokine production in
      the skin following ultraviolet radiation.
AB  - The anti-inflammatory effects of the neuronal nicotinic receptor alpha7
      (nAChRalpha7) are proposed to require acetylcholine release from vagal efferents.
      The necessity for vagal innervation in this anti-inflammatory pathway was tested
      in the skin, which lacks parasympathetic innervation, using ultraviolet radiation
      (UVB) to induce a local pro-inflammatory response. Cytokine responses to UV in
      mice administered chronic oral nicotine, a nAChR agonist, were reduced.
      Conversely, nAChRalpha7 knock-out mice exposed to UVB elicit an enhanced pro
      inflammatory cytokine response in the skin. Altered pro-inflammatory responses
      correlated with changes in SOCS3 protein. These results demonstrate that
      nAChRalpha7 can participate in modulating a local pro-inflammatory response in
      the absence of parasympathetic innervation.

PMID- 18077005
TI  - Foxp3+ regulatory T cells in the control of experimental CNS autoimmune disease.
AB  - The role of T regulatory (Treg) cells expressing the forkhead box transcription
      factor 3 (foxp3) in the control of autoaggressive immune responses is the subject
      of intense investigation. Here we explore the contribution of these cells to the
      regulation of experimental autoimmune encephalomyelitis (EAE). Starting from a
      historical perspective, we review their roles in preventing spontaneous disease,
      in setting the threshold for activation of a pathogenic response and in
      critically mediating the natural recovery from EAE. Current uncertainties and
      controversies are discussed in regard to EAE and multiple sclerosis as well as
      the potential for Treg-targeted immunotherapy.

PMID- 18077006
TI  - Stem cells ameliorate EAE via an indoleamine 2,3-dioxygenase (IDO) mechanism.
AB  - Syngeneic, pluripotent Lin(-)Sca1(+) bone marrow stem cells (SC), transferred to
      mice with experimental autoimmune encephalomyelitis, a model of multiple
      sclerosis, enhanced recovery, prevented relapses and promoted myelin repair. SC
      treated mice showed elevated interferon-gamma production and induction of
      indoleamine 2,3-dioxygenase (IDO) in CD11c(+) dendritic cells (DC). IDO induction
      was specific since in the presence of IDO-producing CD11c(+) DC, PLP stimulated T
      cell proliferation was inhibited and the IDO-inhibitor, 1-MT, abrogated the SC
      effect. Relapse prevention during chronic disease correlated with decreased
      responsiveness to PLP(178-191) and MBP(85-99). Thus, pluripotent SC induce IDO in
      DC leading to inhibition of antigen reactivity and spreading in EAE.

PMID- 18077007
TI  - Development and evaluation of serological assays for detection of Hantaanvirus
      specific antibodies in human sera using yeast-expressed nucleocapsid protein.
AB  - Indirect and capture enzyme-linked immunosorbent assays (ELISAs) for detection of
      Hantaan virus (HTNV)-specific immunoglobulins G (IgG) and M (IgM) in human serum
      samples were developed on the basis of recombinant yeast-expressed nucleocapsid
      (N) protein of HTNV. The sensitivities and specificities of the indirect and
      capture ELISAs were evaluated by comparing the reactivity of sera from patients
      with hemorrhagic fever with renal syndrome (HFRS) from China with that of a
      commercial IgG/IgM kit. The sensitivity of the indirect IgG and IgM ELISA tests
      was both 100% and the specificity of the indirect IgM and IgG ELISA test was 98%
      and 99%, respectively. The sensitivity and specificity of the capture IgM ELISA
      was 100% and 97%, respectively. The novel assays were found to detect HTNV
      specific antibodies in acute phase sera from suspected HFRS patients in China.
      The results indicate that these novel ELISAs are suitable for the diagnosis of
      HTNV and for sero-epidemiological studies.

PMID- 18077008
TI  - Differential effects of vocalization type, singer and listener on ZENK immediate
      early gene response in black-capped chickadees (Poecile atricapillus).
AB  - Here we examined immediate early gene (ZENK) induction to vocalizations in the
      ascending auditory pathway of black-capped chickadees (Poecile atricapillus) to
      assess the impact that the sex of the producer and perceiver has on ZENK
      induction. We manipulated the playback by both the vocal type (song/call) and sex
      of producer (male/female), and then presented these stimuli classes to either
      male or female black-capped chickadees. Neural response to the stimulus was
      quantified by the amount of protein of the IEG ZENK (also known as zif-268, egr
      1, ngf-Ia and krox-24) in the caudal medial nidopallium (NCM) and caudomedial
      mesopallium (CMM). Overall, there was more ZENK induction in CMM and the dorsal
      parts of the caudal medial nidopallium (NCMd) than in the ventral parts of the
      caudal medial nidopallium (NCMv) and males had more ZENK induction than females.
      CMM had the most complex responding of ZENK induction to stimuli such that
      vocalization type, sex of producer, and sex of perceiver all affected ZENK
      induction. The silence controls had the least ZENK induction compared to any
      other group.

PMID- 18077009
TI  - Contour-integration deficits on the intact side of the visual field in hemianopia
      patients.
AB  - OBJECTIVE: Visual impairments in hemianopia are thought to be exclusively caused
      by the reduced visual field size. However, the primary lesion may affect the
      contralateral hemisphere through damage of interhemispheric projections. The
      question therefore arises if the presumed "intact" hemifield is perceptually
      impaired. METHODS: Three hemianopia patients and three matched controls carried
      out a Yes/No figure detection task with their intact side of the visual field.
      The figure (square) contours were composed of non-contiguous Gabor patches
      embedded in a random patch array of different background densities (low, delta=2;
      high, delta=1). Response accuracy and reaction times were recorded. RESULTS: A
      temporal-parietal patient revealed figure detection impairments, with accuracy
      rate, 77% (delta=2) and 53% (delta=1), below compared control values. An
      occipital patient was comparable to his match: 99% (delta=2); 84% (delta=1). Both
      patients exhibited frequent false alarms to random patterns and required longer
      presentation times to perform the task. In the third patient, with optic tract
      lesion, figure detection was nearly normal at low density (92%, delta=2) but
      impaired at noisy background (62%, delta=1). CONCLUSION: The "intact" visual
      field in hemianopes is impaired in detection of incomplete figures embedded in a
      noisy background. This deficit may be caused by damage to higher visual centers
      and/or loss of interhemispheric interactions.

PMID- 18077010
TI  - Species-specific inhibition of Giardia lamblia triosephosphate isomerase by
      localized perturbation of the homodimer.
AB  - Giardia lamblia depends on glycolysis to obtain ATP, highlighting the suitability
      of glycolytic enzymes as targets for drug design. We studied triosephosphate
      isomerase from G. lamblia (GlTIM) as a potential species-specific drug target.
      Cysteine-reactive agents were used as probes, in order to test those regions near
      to cysteine residues as targets to perturb enzyme structure and activity. Methyl
      methanethiosulfonate (MMTS) derivatized three of the five Cys per subunit of
      dimeric GlTIM and induced 50% of inactivation. The 2-carboxyethyl
      methanethiosulfonate (MTSCE) modified four Cys and induced 97% of inactivation.
      Inactivation by MMTS or MTSCE did not affect secondary structure, nor induce
      dimer dissociation; however, Cys modification decreased thermal stability of
      enzyme. Inactivation and dissociation of the dimer to stable monomers were
      reached when four Cys were derivatized by 5,5'-dithio-bis(2-nitrobenzoic acid)
      (DTNB). The effects of DTNB were completely abolished when GlTIM was first
      treated with MMTS. The effect of thiol reagents on human TIM was also assayed; it
      is 180-fold less sensitive than GlTIM. Collectively, the data illustrate GlTIM as
      a good target for drug design.

PMID- 18077011
TI  - VIP inhibits human HepG2 cell proliferation in vitro.
AB  - Hepatocellular carcinoma (HCC) is an aggressive and often fatal neoplasm. HepG2
      cells are a cell line derived from HCC. This investigation shows that vasoactive
      intestinal peptide (VIP) inhibits HepG2 cell proliferation in vitro. In addition,
      VIP decreases the expression of signal transducers and activators of
      transcription-3 (STAT-3) and phosphorylated STAT-3 (pSTAT-3). Transfection of
      HepG2 cells with STAT-3 siRNA also dose-dependently inhibits proliferation. These
      findings suggest that VIP-mediated inhibition of HepG2 proliferation may be
      mediated by STAT-3. Further studies demonstrate that VIP increases HepG2 cAMP
      levels and 8-cl-cAMP inhibits HepG2 proliferation as well as pSTAT-3 and STAT-3
      levels, suggesting that cAMP is also involved in the inhibition of HepG2
      proliferation. VIP also attenuates the proliferative effects of hepatocyte growth
      factor (HGF) and interleukin-6 (IL-6) on HepG2 cells. These preliminary studies
      suggest that the antiproliferative actions of VIP may offer a new and promising
      means of suppressing HCC.

PMID- 18077012
TI  - Effects of vitamin C supplementation on antioxidants and lipid peroxidation
      markers in elderly subjects with type 2 diabetes.
AB  - The objective of our study was to evaluate the effects of the administration of
      two dosages of vitamin C (Vit-C) (0.5 and 1g/day, vs. placebo) in elderly
      patients with type 2 diabetes mellitus on the intracellular levels of Vit-C and
      glutathione, and on the lipid peroxidation markers and vitamin E (Vit-E) content
      of low-density lipoprotein (LDL) and on LDL susceptibility to gamma radiolysis
      induced peroxidation. Thirty-six patients were randomized into three groups. In
      patients on 0.5 g Vit-C/day versus the placebo group, a significant increase in
      cellular reduced glutathione level was observed (0.60+/-0.26 vs. 0.33+/-0.27). In
      patients on 1 g Vit-C/day versus placebo, a significant increase was also
      observed in cellular reduced glutathione (0.93+/-0.70 vs. 0.33+/-0.27), in Vit-C
      (5.66+/-2.00 vs. 2.72+/-1.88) and in vitamin E content of LDL (1.98+/-0.38 vs.
      1.48+/-0.40). No change was observed in either group in basal levels of lipid
      peroxidation markers and in the susceptibility of LDL to peroxidation provoked by
      gamma-radiolysis. In conclusion, Vit-C has a dose-dependent effect on the
      cellular contents of antioxidants and on vitamin E content of LDL in elderly
      patients with type 2 DM. These changes are not sufficient to decrease the LDL
      susceptibility to peroxidation.

PMID- 18077013
TI  - Increased B-type natriuretic peptide is associated with an abnormal blood
      pressure response to exercise in asymptomatic aortic stenosis.
AB  - AIMS: Both raised plasma levels of B-type natriuretic peptide (BNP) and an
      abnormal exercise response predict adverse clinical outcomes in aortic stenosis
      (AS). This study examines the relationship between the response to treadmill
      exercise and plasma levels of BNP in AS. METHODS AND RESULTS: 34 asymptomatic
      patients with moderate or severe AS (mean valve area 0.96+/-0.3 cm(2)) and 15 age
      matched controls underwent echocardiography, treadmill exercise testing, and BNP
      analysis. Compared to control subjects, AS patients had a higher left ventricular
      mass index, (133+/-50 vs 106+/-24 g/m(2), p=0.03), higher E/E' ratio, (10.6+/-3.6
      vs 6.7+/-1.8, p=<0.0001), higher ejection fraction, (65+/-6 vs 59+/-6%, p=0.03),
      elevated resting BNP (11.4+/-6.5 vs 7.4+/-4.0 pmol/L, p=0.03) and shorter
      exercise duration (8.2+/-3.0 min vs 10.9+/-2.6 min, p=0.002). AS patients with an
      increase in systolic BP of <or=20 mmHg during exercise (n=18) had higher plasma
      levels of BNP than patients with an increase in systolic BP >20 mmHg (13.8+/-6.1
      vs 8.6+/-6.0 pmol/L, p=0.003). The BNP measured at peak exercise was also
      associated with the BP response (p=0.003). The area under the receiver operator
      curve to predict an abnormal BP response to exercise was 0.82 for BNP measured at
      rest but only 0.46 for aortic valve area. There was a modest association between
      raised BNP and lower exercise capacity. CONCLUSION: In patients with AS there is
      an association between BNP and an abnormal BP response to exercise. Further study
      is needed to determine the incremental prognostic value of BNP and exercise
      testing in asymptomatic AS.

PMID- 18077014
TI  - Polyamine metabolism in rat myocardial ischemia-reperfusion injury.
AB  - This study was focused on investigating the involvement of polyamine metabolism
      in the myocardial ischemia-reperfusion injury (MIRI) in an in vivo rat model. A
      branch of the descending left coronary artery was occluded for 30 min followed by
      2 h, 6 h, 12 h, and 24 h reperfusion. Then the expression of spermidine/spermine
      N1-acetyltransferase (SSAT) and ornithine decarboxylase (ODC) and the
      concentrations of polyamines were assessed. It was found that the expression of
      SSAT and ODC were upregulated after reperfusion and the concentrations of
      spermidine and spermine were significantly decreased, while putrescine
      concentration was significantly increased. The results suggest that MIRI may
      cause disturbance of polyamine metabolism, and it may play a critical role in
      MIRI.

PMID- 18077015
TI  - Detection of acute pulmonary edema by cardiac magnetic resonance in a patient
      with dilated cardiomyopathy and idiopathic pulmonary artery ectasia.

PMID- 18077016
TI  - Could chewing garlic reveal clinical efficacy?

PMID- 18077017
TI  - Identifying AF patients at risk of stroke: can prothrombotic indices improve
      things?

PMID- 18077018
TI  - Gender differences of success rate of percutaneous coronary intervention and
      short term cardiac events in Korea Acute Myocardial Infarction Registry.
AB  - BACKGROUND AND OBJECTIVES: The first on-line prospective, open and observational
      registration, Korea Acute Myocardial Infarction Registry (KAMIR), has been
      carried out throughout 41 primary percutaneous coronary intervention (PCI)
      centers by the support of the Korean Circulation Society (KCS) in the memorandum
      of the 50th Anniversary of the KCS. SUBJECTS AND METHODS: Between Nov 2005 and
      Aug 2006, 5624 enrolled patients (3925 male, 1699 female; age=64.0+/-13.0 years)
      were analyzed. The treatment strategy of acute myocardial infarction (AMI) was
      analyzed according to the sex differences in the field of acute ST-segment
      elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial
      infarction (NSTEMI). RESULTS: In the initial selection of treatment strategy,
      invasive treatment was more commonly performed in males than females with both
      STEMI and NSTEMI (82.0% vs. 78.7%, p=0.001; 50.4% vs. 43.7%, p=0.004). Severe
      heart failure was the most important predictor of invasive treatment after
      multivariate adjustment. During hospital stay, PCI regardless of its subtype was
      more frequently performed in males than in females with both STEMI and NSTEMI
      (STEMI: 89.5% vs. 84.7%, p<0.001; NSTEMI: 77.0% vs. 66.7%, p<0.001). Success rate
      of PCI in STEMI was not different between the sexes (95.8% vs. 93.8%, p=0.075),
      but that of NSTEMI was higher in males than females (96.8% vs. 95.6%, p=0.005).
      Major adverse cardiac events (MACE) developed more frequently in women than men
      with both STEMI (9.2% vs. 17.0%, p<0.001) and NSTEMI (7.3% vs. 12.0%, p<0.001)
      during 1 month clinical follow-up. CONCLUSIONS: In the initial treatment of AMI
      in Korea, there is no gender difference for invasive treatment. However, success
      rate of PCI in NSTEMI was lower and 1 month MACE was higher in females than males
      in Korea.

PMID- 18077019
TI  - Stenting versus plain old angioplasty in patients with ST segment elevation
      myocardial infarction: understanding of the randomized trials.

PMID- 18077020
TI  - Acute subarachnoid haemorrhage as a precipitant for takotsubo cardiomyopathy: a
      case report and discussion.
AB  - Takotsubo cardiomyopathy is a recently recognised acute cardiac entity. It
      involves transient left ventricular apical ballooning, which is usually preceded
      by an episode of physiological or emotional stress. Its presentation may mimic
      acute myocardial infarction but there is no evidence of obstructive disease at
      coronary angiography. The aetiology of this condition has not been clearly
      defined, though a number of hypotheses have been put forward. Precipitating
      factors vary widely, including acute medical conditions and emotional stressors.
      We present a case of takotsubo cardiomyopathy precipitated by acute subarachnoid
      haemorrhage, the first report of this association in a Caucasian patient, and
      discuss the implications for clinicians involved in the management of such a
      case.

PMID- 18077021
TI  - Dark side of drug-eluting stent: multiple stent fractures and sudden death.
AB  - Recently reported stent fractures after sirolimus-eluting stent (SES)
      implantation were found several months later during the follow-up of coronary
      angiogram (CAG) and single fracture mostly. The study reports a case of
      sequential, continuous, multiple coronary stent fracture and sudden death.

PMID- 18077022
TI  - Hyperintensity on T2-weighted magnetic resonance imaging in Takotsubo
      cardiomyopathy.
AB  - The mechanism underlying the association between Takotsubo cardiomyopathy (TC)
      and myocardial injury is unknown. We describe a signal hyperintensity zone on T2
      weighted magnetic resonance imaging (T2WI) in 2 cases of atypical and typical TC.
      In these cases, a transmural hyperintensity zone on T2WI agrees with a region of
      abnormal left ventricular wall motion. We suggest that edematous viable
      myocardium is present transmurally in the acute phase of TC.

PMID- 18077023
TI  - Retrograde approach to recanalising coronary chronic total occlusions immediately
      following a failed conventional attempt.
AB  - Chronic total occlusions (CTO) continue to be associated with worse procedural
      outcomes following percutaneous coronary intervention (PCI) compared with non
      occlusive lesions. A number of advances in materials and novel techniques have
      helped improve procedural success and have stimulated renewed interest in CTO
      PCI. We present 2 cases in which a conventional antegrade attempt was
      unsuccessful and resulted in considerable dissection distal to the occlusion. In
      both patients we employed a retrograde approach using septal collaterals to cross
      the occlusions retrogradely. This approach proved successful and can be
      applicable in patients with suitable collateral channels following unsuccessful
      conventional procedures, even in the same session.

PMID- 18077024
TI  - Evaluation of the NucliSens miniMAG RNA extraction and real-time NASBA
      applications for the detection of Mycoplasma pneumoniae and Chlamydophila
      pneumoniae in throat swabs.
AB  - Nucleic acids were extracted from 215 throat swabs from patients with community
      acquired pneumonia by the manual Boom extraction, the NucliSens miniMAG and the
      Qiagen DNA blood kit and amplified respectively by in-house real-time NASBA,
      NucliSens EasyQ reagents, and real-time PCR for the detection of Mycoplasma
      pneumoniae and Chlamydophila pneumoniae. Five out of 215 throat swabs were found
      to be C. pneumoniae positive by all techniques used. A total of 11 out of 215
      throat swabs were positive for M. pneumoniae; 10/215 by Qiagen extraction and PCR
      amplification and 9/215 by NucliSens miniMAG and NucliSens EasyQ amplification.
      The NucliSens miniMAG and NucliSens EasyQ applications were successfully coupled
      to detect both organisms in throat swabs.

PMID- 18077025
TI  - Real-time PCR quantification of Dehalococcoides populations: methods and
      applications.
AB  - Dehalococcoides species are responsible for the reductive dehalogenation of an
      impressive range of common, persistent environmental contaminants. These
      microorganisms are difficult to both obtain and grow in pure culture, and so are
      often studied while they exist in consortia using molecular techniques. In
      particular, a significant number of quantitative real-time PCR (qPCR) assays
      targeting Dehalococcoides spp. have been reported. Initial qPCR methods targeted
      the 16S rRNA gene, however, because strains with the same 16S rRNA gene sequence
      can have different dehalogenating abilities, reductive dehalogenase genes are now
      emerging as the most appropriate qPCR target. Quantitative PCR has been critical
      to our current understanding of Dehalococcoides populations; it has provided
      information on their growth characteristics, dehalogenating abilities and
      effective use in bioremediation efforts. Future qPCR research directions will
      likely involve method standardization, as well as continued research on the
      functional genes associated with Dehalococcoides populations.

PMID- 18077026
TI  - A faster and more accurate assay for intracellular replication of Legionella
      pneumophila in amoebae hosts.
AB  - A faster, more sensitive, and more accurate method to study intracellular
      replication of Legionella pneumophila in amoeboid hosts is described. This assay
      relies on an automated plate-reader to examine the intracellular growth and
      release of bacteria in real-time. Our experiments using this method have already
      revealed new insights into the kinetics of intracellular replication of L.
      pneumophila in Acanthamoeba castellanii.

PMID- 18077027
TI  - Optimization of electrotransformation conditions for Propionibacterium acnes.
AB  - Propionibacterium acnes has been known to be involved in the pathology of acne.
      However, the definite mechanism in the development of acne and the inflammation
      are unknown. For P. acnes, a transformation method has not been established,
      although it is believed to be a basic tool for gene manipulation. This study
      attempted to develop a P. acnes transformation method by using electroporation.
      Various parameters were used to develop and optimize the transformation of P.
      acnes. Among them two factors were crucial in the transformation for P. acnes:
      one was the E. coli strain from which the plasmid DNA had been isolated and the
      other the growth temperature of P. acnes-competent cells. It was essential to
      prepare plasmid DNA from a dam(-) E. coli strain, ET12567. When plasmid DNAs
      isolated from the other E. coli strains such as JM109 and HB101 were tested,
      transformation efficiency was extremely low. When P. acnes cells were cultivated
      at 24 degrees C for competent cell preparation, transformation efficiency
      increased considerably. When plasmid DNA isolated from a dam(-) mutant strain of
      E. coli was used for transformation of P. acnes which had been grown at 24
      degrees C, maximum transformation efficiency of 1.5 x 10(4) transformants per mug
      of plasmid DNA was obtained at a field strength of 15 kV/cm with a pulse time of
      3.2 ms. This is believed to be the first report on the transformation of P. acnes
      which can be employed for gene manipulations including knock-out of specific
      genes.

PMID- 18077028
TI  - Exhale fluctuation in respiratory-gated radiotherapy of the lung: a pitfall of
      respiratory gating shown in a synchronized internal/external marker recording
      study.
AB  - PURPOSE: For optimal respiratory-gated radiotherapy, exhale fluctuation was
      assessed by monitoring internal fiducials in a synchronized internal/external
      marker detection system. METHODS: Synchronized internal/external position data
      were collected during the entire course of treatments for 12 lung patients with
      24 fiducials. Baseline was determined in the exhale phase during pre-treatment
      observation time, and a gating level of external waves was set in each treatment
      session in a simulation of respiratory-gated radiotherapy. Patients were treated
      under a real-time tumor-tracking (RTRT) system with an external (abdominal)
      respiratory motion detector. In the simulation, external gating windows were
      defined as those below the 30% amplitude level (i.e., imaginary beams would be
      triggered when part of the respiratory wave falls into this window). Exhale
      fluctuation (EF) was defined as the phenomenon in which the lowest point of the
      external wave crossed downward past the pre-determined baseline. Gating
      efficiency (GE) was defined as the ratio between the amount of gate-ON time and
      the total treatment time. RESULTS: EF occurred in 18.4% of total measurements. EF
      varied depending on the patient, fiducial sites, and treatment session. The mean
      incidence of EF for each patient varied from 2.9% to 37.5% (18.4+/-9.9). The EF
      magnitude was 0.2-12.2 mm in the left-right direction, 0.7-12.7 mm in the cranio
      caudal direction, and 0.4-9.7 mm in the anterior-posterior direction. Total
      fiducial movement was 0.5-28.7 mm. GE was 36.1-69.2% (55.4+/-11.0). EF magnitude
      correlated with total fiducial movement. CONCLUSION: This study showed that EF is
      not a rare phenomenon and needs to be taken into consideration for individualized
      precise 4D radiotherapy.

PMID- 18077029
TI  - Tissue oxygenation in a murine SCC VII tumor after X-ray irradiation as
      determined by EPR spectroscopy.
AB  - PURPOSE: The goal of this study was to clarify the dynamics of oxygenation
      (partial pressure of oxygen, pO(2)) in SCC VII murine tumors in mice after X-ray
      irradiation. MATERIALS AND METHODS: Changes in pO(2) in tumors were measured by
      1.2-GHz electron paramagnetic resonance (EPR) spectroscopy after they were
      exposed to various doses of irradiation. The pO(2) in tumors was followed for up
      to six days after irradiation at doses of 0, 5, 10, 15, and 20 Gy. Paramagnetic
      crystals were used as an oximetry probe and implanted into normal or tumor
      tissues in mice for prolonged periods. RESULTS: The pattern of tumor oxygen after
      a single dose of radiation with the 5-Gy dose was different from those with other
      doses (10, 15, and 20 Gy). After 5 Gy, pO(2) increased rapidly (P<0.01, Student's
      t test) and then returned to the level observed before irradiation by 12h
      (P<0.01). In contrast, after 10, 15, or 20 Gy, pO(2) increased rapidly by 6h
      after irradiation, continued to increase until at least 24h (P<0.01), and then
      gradually decreased. CONCLUSIONS: In tumors that received 5 Gy, post-irradiation
      increases in pO(2) at 4h after irradiation were detected by EPR oximetry (P<0.01)
      noninvasively.

PMID- 18077031
TI  - A study of tumor motion management in the conformal radiotherapy of lung cancer.
AB  - PURPOSE: To assess the benefit derived from the reduction of planning target
      volumes (PTVs) afforded by tumor motion management in treatment planning for lung
      cancer. METHODS: We use a simple formula that combines measurements of tumor
      motion and set-up error for 7 patients to determine PTVs based on the following
      scenarios: standard uniform 15 mm margin, individualized PTVs (no gating),
      spirometry-based gating, and active breath-control (ABC). We compare the percent
      volumes of lung receiving at least 20 Gy (V20) for a standard prescription, and
      the maximum tolerated doses (MTDs) at fixed V20. In anticipation of improvements
      in set-up accuracy, we repeat the analysis assuming a reduced set-up margin of
      3mm. RESULTS: Relative to the standard, the average percent reductions in V20 (+/
      1 standard deviation) for the ungated and gated scenarios are 17+/-5 and 21+/-8;
      the percent gains in MTD are 25+/-12 and 33+/-11, respectively. For the 3mm set
      up margin, the corresponding results for V20 are 28+/-7 and 36+/-7, and for MTD
      are 57+/-23 and 79+/-31. CONCLUSIONS: Any form of motion management provides a
      benefit over the use of a standard margin. The benefit derived from gating
      compared to the use of ungated individualized PTVs increases with tumor mobility
      but is generally modest. While motion management may benefit patients with highly
      mobile tumors, we expect efforts to reduce set-up error to be of greater overall
      significance. The practical limit for lung PTV margins is likely around 4-5mm,
      provided set-up error can be reduced sufficiently.

PMID- 18077030
TI  - PAI-1 levels predict response to fractionated irradiation in 10 human squamous
      cell carcinoma lines of the head and neck.
AB  - BACKGROUND AND PURPOSE: To investigate the relationships between hypoxia, VEGF
      and components of the plasminogen activation system (PAS) and to determine their
      influence on local tumour control after fractionated radiotherapy. MATERIAL AND
      METHODS: Ten cell lines derived from human squamous cell carcinomas of the head
      and neck (SCCHN) were investigated in vitro and used to generate xenograft
      tumours. The pimonidazole hypoxic fraction in the total tumour area (pHF(tot))
      was used to measure hypoxia in pre-treatment tumours and the local tumour control
      (TCD(50)) was used as the functional endpoint in vivo. For in vitro experiments,
      cells were cultured for 24h under either normoxic or mild hypoxic ( approximately
      0.66% O(2)) conditions. VEGF, PAI-1 and uPA antigen levels were determined by
      ELISA and uPA activity by an activity assay kit. RESULTS: Of all the factors
      investigated, only PAI-1 expression correlated with TCD(50) (r=0.80, p=0.010) and
      was significantly higher (p=0.001) in more hypoxic than in less hypoxic tumours.
      Accordingly, PAI-1 secretion was significantly induced (2.4x) by in vitro
      hypoxia. CONCLUSIONS: These results suggest that pre-treatment PAI-1 levels are
      higher in more hypoxic tumours and can predict the response to fractionated
      irradiation in SCCHN.

PMID- 18077032
TI  - Concurrent radiation therapy and lenalidomide in myeloma patient.

PMID- 18077033
TI  - Simultaneous tumour dose escalation and liver sparing in Stereotactic Body
      Radiation Therapy (SBRT) for liver tumours due to CTV-to-PTV margin reduction.
AB  - PURPOSE: To quantify potential benefits of CTV-to-PTV margin reduction for SBRT
      of liver tumours, as allowed by enhanced treatment precision. MATERIALS AND
      METHODS: For 14 patients plans were generated for the clinical margin and for 3
      tighter margins. An in-house developed algorithm was used to optimise beam
      directions, shapes, and weights for generation of the plan with the highest
      isocenter dose (D(iso)), while keeping the minimum PTV dose at least 65%xD(iso)
      and strictly adhering to all imposed hard OAR constraints. Each plan contains 10
      optimal beam directions, automatically selected from up to 252 coplanar and non
      coplanar input directions. RESULTS: Apart from the expected tumour dose
      escalation (D(iso), EUD(PTV), gEUD(PTV)) with decreasing margin, a simultaneous
      improved sparing of the normal liver (D33%, D50%, D(mean)) was also observed. The
      smaller the margin was, the bigger both effects were. For renormalized plans with
      D(iso) equal to the clinical value (3x19.2Gy), and a margin reduction of 50%
      (2.5mm laterally, 5mm longitudinally), normal liver D33% and D50% reduced on
      average by 22% (maximum 38%), and 26% (maximum 47%), respectively. CONCLUSIONS:
      Using an algorithm for beam direction, shape and weight optimisation, large
      increases in the therapeutic ratio of liver plans could be obtained for reduced
      margins.

PMID- 18077034
TI  - Detailed review and analysis of complex radiotherapy clinical trial planning
      data: evaluation and initial experience with the SWAN software system.
AB  - AIM: Contemporary radiotherapy clinical trials typically require complex three
      dimensional (3D) treatment planning. This produces large amounts of data relating
      technique and dose delivery for correlation with patient outcomes. Assessment of
      the quality of this information is required to ensure protocol compliance, to
      quantify the variation in treatments given to patients and to enhance the power
      of studies to determine correlates of patient outcomes. MATERIALS AND METHODS: A
      software system ('SWAN') was developed to facilitate the objective analysis,
      quality-assurance and review of digital treatment planning data from multi-centre
      radiotherapy trials. The utility of this system was assessed on the basis of its
      functionality and our experience of its use in the context of multi-centre
      clinical trials and trials-support activities. RESULTS: The SWAN system has been
      shown to have the functionality required for use in several multi-centre trials,
      including automated review and archive processes. Approximately 800 treatment
      plans from over 30 participating institutions have so far been assessed with the
      system for several treatment planning scenarios. To illustrate this we include a
      description of the use of the system for a large-recruitment prostate
      radiotherapy trial being undertaken in Australasia, including examples of how the
      review process has changed clinical practice. CONCLUSION: The successful
      implementation of SWAN has been demonstrated in a number of clinical trials. The
      software provides an opportunity for comprehensive review of treatment parameters
      that could impact on clinical outcomes and trial results. Such quality-assurance
      (QA) has previously been difficult or impossible to achieve, particularly for a
      clinical trial involving large numbers of patients. Such reviews have highlighted
      inconsistencies in clinical practice that have since been addressed through
      feedback from the review process. The process of data collection and review
      should be undertaken by dedicated, experienced and skilled staff in order to
      ensure efficiency.

PMID- 18077035
TI  - Effects of rat medial prefrontal cortex lesions on olfactory serial reversal and
      delayed alternation tasks.
AB  - When reward reinforcement in a two-choice discrimination task is regularly
      changed from one stimulus to another immediately after one learning acquisition
      session, the learning efficiency of a rat increases as if the rat has come to
      recognize this regularity of reversal. To investigate how the rat medial
      prefrontal cortex (mPFC) is involved in such improvement, we examined the
      performance of mPFC-lesioned rats in a serial reversal task of olfactory
      discrimination. The performance of other mPFC-lesioned rats in a delayed
      alternation task was also analyzed using the same apparatus to evaluate the
      contribution of the mPFC to working memory. The mPFC-lesioned rats demonstrated
      selective difficulty in the second reversal session in the serial reversal task
      and also showed performance impairment in the delayed alternation task. These
      results suggest that the rat mPFC mediating working memory is involved in early
      progress in learning efficiency during experiences of multiple reversals, which
      may be relevant to cognitive operations in reversal learning beyond a one-time
      reversal of stimulus response associations.

PMID- 18077036
TI  - Survival patterns of Dekkera bruxellensis in wines and inhibitory effect of
      sulphur dioxide.
AB  - The wine spoilage yeast species Dekkera bruxellensis, after inoculation in red
      wines, displayed three survival patterns characterized by: i) initial lag phase
      followed by growth and sequential death; ii) initial death phase leading to
      reduced viable counts followed by growth and sequential death; and iii) death
      phase leading to complete loss of viability. These survival patterns were
      observed for the same strain in different dry red wine blends with 12% (v/v)
      ethanol and pH 3.50, in the absence of free sulphur dioxide. For the same wine
      blend, these patterns also varied with the tested strain. Under laboratory
      conditions the addition of 150 mg/l of potassium metabisulphite (PMB) to dry red
      wine with 12% (v/v) ethanol and pH 3.50 reduced initial cell counts by more than
      6 logarithmic cycles, inducing full death within less than 24 h. Winery trials
      showed that D. bruxellensis blooms were only prevented in the presence of about
      40 mg/l of free sulphur dioxide in dry red wine, with 13.8% (v/v) ethanol and pH
      3.42, matured in oak barrels. These different amounts of PMB and sulphur dioxide
      corresponded to about 1 mg/l of molecular sulphur dioxide. Our results therefore
      demonstrate that the control of populations of D. bruxellensis growing in red
      wine can only be achieved under the presence of relatively high doses of
      molecular sulphur dioxide.

PMID- 18077037
TI  - Lactobacillus fermentum ACA-DC 179 displays probiotic potential in vitro and
      protects against trinitrobenzene sulfonic acid (TNBS)-induced colitis and
      Salmonella infection in murine models.
AB  - Lactobacillus fermentum ACA-DC 179, Lactobacillus plantarum ACA-DC 287 and
      Streptococcus macedonicus ACA-DC 198 were studied for their probiotic potential.
      Firstly, strains were screened for antimicrobial activity towards a broad range
      of target strains, including lactic acid bacteria, food spoilage and pathogenic
      bacteria. L. fermentum ACA-DC 179 was active against five streptococci, including
      the two pathogenic strains Streptococcus oralis LMG 14532T and Streptococcus
      pneumoniae LMG 14545T. S. macedonicus ACA-DC 198 was active against the majority
      of the strains tested, including not only lactic acid bacteria but also many food
      spoilage or pathogenic species. The three potential probiotic strains were found
      to survive variably at pH 2.5 and were unaffected by bile salts. Only S.
      macedonicus ACA-DC 198 exhibited bile salt hydrolase activity, while none of the
      strains was haemolytic. Moreover, strains exhibited variable susceptibility
      towards commonly used antibiotics. L. plantarum ACA-DC 287 and S. macedonicus ACA
      DC 198 induced the secretion of the pro-inflammatory cytokines IL-12, IFN-gamma
      and TNF-alpha by human peripheral blood mononuclear cells. Also elevated levels
      of the anti-inflammatory IL-10 were observed with L. fermentum ACA-DC 179. This
      strain consequently was found to significantly reduce colitis in a TNBS-induced
      colitis mouse model. Furthermore, L. fermentum ACA-DC 179 was successfully
      applied in an experimental Salmonella-infection mouse model. To conclude, strain
      L. fermentum ACA-DC 179 possesses desirable probiotic properties, such as
      antimicrobial activity and immunomodulation in vitro, which were confirmed in
      vivo by the use of animal models.

PMID- 18077038
TI  - Reduction of lipids in fish meal prepared from fish waste by a yeast Yarrowia
      lipolytica.
AB  - The high lipid content in fish waste is one of the reasons why fish meal made
      from fish waste is commercially rated as low grade meal. Microorganisms which
      have the ability to reduce crude lipids from samples of minced fish in solid
      state fermentation were screened and a strain of Yarrowia lipolytica showed the
      highest efficiency for reducing the lipids by 29%. The lipid reduction by this
      strain was especially affected by the ratio of surface area to the weight in the
      fermented mince samples and by the water content, suggesting the importance of
      the oxygen supply. In the fermentation with intermittent mixing during 96 h
      incubation, reduction efficiency for crude lipids came to 46% but that for
      protein was less than 1%. With the fermentation, 41.5 g of crude lipids in 1 kg
      of the minces were estimated to be reduced to 22.4 g, indicating increase of
      protein content in the final product. Furthermore, the carbonyl value which is an
      indicator of lipid oxidation was relatively suppressed by the fermentation. These
      results suggest that the fermentation can improve the quality of fish meal from
      fish waste which is rich of lipids.

PMID- 18077039
TI  - Bacterial biodiversity of traditional Zabady fermented milk.
AB  - The aim of this work was to identify the bacterial biodiversity of traditional
      Zabady fermented milk using PCR-temporal temperature gel electrophoresis (PCR
      TTGE) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE). Most of the
      identified bacterial species in Zabady samples belonged to lactic acid bacteria
      (LAB), e.g., Streptococcus thermophilus, Lactococcus garvieae, Lactococcus
      raffinolactis, Lactococcus lactis, Leuconostoc citreum, Lactobacillus delbrueckii
      subsp. bulgaricus and Lactobacillus johnsonii. Using the culture-dependent and
      independent methods, the streptococcal and lactococcal groups appeared to be the
      major bacterial species in Zabady fermented milk, whereas the lactobacilli were
      the minor ones. The main dominant species was St. thermophilus followed by Lc.
      garvieae. Other molecular tools, e.g., species-specific PCR assay and cloning and
      sequencing strategy were used to confirm the TTGE and DGGE results. Lc. garvieae,
      Lc. raffinolactis, Ln. citreum, and Lb. johnsonii were identified for the first
      time in this type of Egyptian fermented milk.

PMID- 18077040
TI  - Shelf-life of minimally processed lettuce and cabbage treated with gaseous
      chlorine dioxide and cysteine.
AB  - Gaseous ClO2 was evaluated for effectiveness in prolonging the shelf-life of
      minimally processed (MP) lettuce and MP cabbage, previously immersed in a
      cysteine solution in order to inhibit browning occurring during ClO2 treatment.
      Each vegetable was shredded, washed, and separated in two portions, one to be
      treated with ClO2 gas and the other to remain untreated as reference sample. The
      batch to be treated with ClO2 gas was immersed for 1 min in a 0.5% solution of
      HCl.L-cysteine monohydrate. Then both batches were spun dried. MP vegetables were
      decontaminated in a cabinet at 90-91% relative humidity and 22-25 degrees C up to
      10 min, including 30 s of ClO2 injection into the cabinet. The ClO2 concentration
      rose to 1.74 mg/L (MP lettuce) and 1.29 mg/L (MP cabbage). Then samples were
      stored under modified atmosphere at 7 degrees C for shelf-life studies. Changes
      in O2 and CO2 headspace concentrations, microbiological quality (aerobic plate
      count (APC), psychrotrophs, lactic acid bacteria, and yeasts), sensory quality,
      and pH were followed during storage. The respiration rate of the minimally
      processed vegetables was significantly increased by the ClO2 gas treatment only
      in the case of MP cabbage (P<0.05). The gas treatment reduced initially APC and
      psychrotroph count of MP lettuce and APC, psychrotroph counts, yeast counts and
      pH of MP cabbage (P<0.05). ClO2 treatment did not cause initially any significant
      (P<0.05) sensorial alteration, except for a weak off-odour in MP lettuce.
      Interestingly, no browning was observed after treating, which can be accounted to
      the use of L-cysteine. Although an initial microbiological reduction was observed
      due to ClO2 gas treatment, APC and psychrotroph counts reached in the samples
      treated with ClO2 higher levels than in those non-treated with ClO2 before the
      third day of the shelf-life study. Untreated and treated samples of MP lettuce
      were sensorial unacceptable due to bad overall visual quality after 4 days, while
      treated and untreated MP cabbage remained sensorial acceptable during the 9 days
      of the study. L-cysteine reduced (P<0.05) the decontamination efficacy of ClO2
      when applied to MP cabbage but not in the case of MP lettuce. Gaseous ClO2 failed
      to prolong the shelf-life of MP lettuce and MP cabbage, the reason for the
      enhanced growth of microorganisms in decontaminated samples should be
      investigated. Nonetheless, our results prove that it is possible to inhibit
      browning caused by ClO2.

PMID- 18077041
TI  - The occurrence of Bacillus cereus, B. thuringiensis and B. mycoides in Chinese
      pasteurized full fat milk.
AB  - In 2006, a total of 54 samples of pasteurized full fat milk packaged in cartons
      were collected in spring and in autumn from chain supermarkets in Wuhan, China.
      The samples were examined and enumerated by MPN methods strictly according to
      guidelines laid out in US FDA/CFSAN BAM Chapter 14. Among 102 isolated B. cereus
      like bacteria, 92 isolates were identified to be B. cereus, 9 B. thuringiensis
      and 1 B. mycoides. It was found that the occurrences of B. cereus were 71.4% and
      33.3% in spring and in autumn samples respectively and the average count among
      the positive samples was 11.7 MPN/ml. The PCR detection results revealed that the
      enterotoxin genes hblA, hblC, hblD, nheA, nheB and nheC occurred in B. cereus
      isolates with frequencies of 37.0%, 66.3%, 71.7%, 71.7%, 62.0% and 71.7%
      respectively. Nine B. thuringiensis isolates were also identified from six
      pasteurized milk samples, and most of them harbored six enterotoxic genes and the
      insecticidal toxin cry1A gene. The single B. mycoides isolate harbored nheA and
      nheC genes. The data provides information for further evaluating the effect of B.
      cereus-like bacteria on food safety of Chinese milk products.

PMID- 18077042
TI  - Fungistatic activity of flaxseed in potato dextrose agar and a fresh noodle
      system.
AB  - Although numerous researchers have studied flaxseed as a food ingredient for its
      health benefits, flaxseed (Linum usitatissimum) has never been considered as a
      food preservative. The objective of this study was to investigate the effect of
      flaxseed flour (FF) concentration (0, 6, 9, 12, and 15% wt/wt), cultivar ('Omega'
      and brown) and source (four seed companies located in Minnesota and North Dakota)
      on flaxseed fungistatic activity. Fungal radial growth was used to assess the
      fungistatic activity of FF in both potato dextrose agar (PDA) medium and a fresh
      noodle system. Strains of Penicillium chrysogenum, Aspergillus flavus, Fusarium
      graminearum, and a Penicillium sp. isolated from molded noodles were used as the
      test microorganisms. Results showed that growth of F. graminearum was completely
      inhibited at all FF concentrations in PDA, and the inhibition of the other three
      test microorganisms increased with increasing FF concentrations. In the model
      noodle system, FF concentration at 9% or higher significantly reduced the mold
      count of fresh noodle during storage. In the inoculated noodle system, 6% FF
      addition was sufficient to significantly inhibit the growth of F. graminearum and
      A. flavus, whereas 9% FF concentrations showed fungistatic activity against P.
      chrysogenum and the Penicillium sp. isolate. Differences in the degree of mold
      inhibition were found among FFs obtained from different sources and cultivars.
      Results suggested that flaxseed possesses fungistatic activity and could be used
      as a multifunctional food ingredient.

PMID- 18077043
TI  - Determination of killer activity in yeasts isolated from the elaboration of
      seasoned green table olives.
AB  - In this work 51 yeasts strains isolated from seasoned green table olives and
      belonging to the Candida, Debaryomyces, Kluyveromyces, Pichia, and Saccharomyces
      genera were characterized by their killer activity in different conditions.
      Killer activity of isolates was analyzed in a medium with different pH's (3.5 to
      8.5) and NaCl concentrations (5, 8, and 10%). At every pH tested, all the genera
      studied had killer strains, although the smallest percentages of killer yeasts
      were found at the highest pH (8.5). The presence of 5 and 8% NaCl increased the
      detected killer percentage, but the highest salt concentration (10%) decreased
      it. The interaction between the reference killer yeasts and yeasts isolated from
      olives was analyzed. Most isolates were killer-sensitive to one or more killer
      reference strains. Only 2 of the 51 strains tested were considered killer
      neutral. Cross-reaction trials between isolates and spoilage yeasts showed that,
      of the isolates, nine killer strains, belonging to Debaryomyces hansenii,
      Kluyveromyces marxianus, Pichia anomala, Pichia guilliermondii, and Saccharomyces
      cerevisiae, had the broadest spectra of action against yeasts that cause
      spoilage. These killer yeasts and the toxins that they produce are candidates for
      further investigation as suppressors of indigenous olive table yeast growth. The
      results confirmed the highly polymorphic expression of the killing activity, with
      each strain showing different killer activities. This method may thus be very
      useful for simple and rapid characterization of yeast strains of industrial
      interest.

PMID- 18077044
TI  - Antifungal activity of Lactobacillus paracasei ssp. tolerans isolated from a
      sourdough bread culture.
AB  - Lactic acid bacteria were isolated from four different sourdough bread cultures
      previously investigated for antifungal activity. A total of 116 isolates were
      obtained and screened for antifungal activity against a battery of molds. The
      most inhibitory isolate obtained was identified by API 50 CHL and 16s ribosomal
      RNA genotyping and found to be Lactobacillus paracasei ssp. tolerans. This
      isolate completely inhibited the growth of Fusarium proliferatum M 5689, M 5991
      and Fusarium graminearum R 4053 compared to controls in a dual agar plate assay.

PMID- 18077045
TI  - Impact of consumption of probiotic lactobacilli-containing yogurt on microbial
      composition in human feces.
AB  - An in vivo study was carried out to determine the effect of consuming probiotic
      lactobacilli-containing yogurt on the composition of microbiota in the human gut.
      Fifteen healthy adults ingested a daily serving of one of three commercial
      yogurts (two of the products contained a probiotic lactobacilli strain) for 20
      days. Fecal samples at defined time points before, during, and after the period
      of yogurt ingestion were collected and analyzed. The fecal population of
      lactobacilli was determined by a culture-based method and subsequent colony PCR
      for the identification of species. Six predominant bacterial groups in the fecal
      samples were quantitatively determined based on a sequence-specific SSU rRNA
      cleavage method coupled with a suite of oligonucleotide probes, which was
      optimized for the target-specific detection of bacterial groups inhabiting human
      feces. In the ingestion period, one probiotic strain was detected in the feces of
      all five subjects who consumed the yogurt containing the strain, while the other
      strain was detected in three of another five subjects. The population levels of
      the two major groups (Bacteroides and Prevotella, and the Clostridium coccoides
      Eubacterium rectale group) in the fecal samples tended to change in response to
      the ingestion but the change did not seem to be dependent on the product-specific
      property of each yogurt. These results suggest that the human fecal bacterial
      community could be altered by ingesting yogurt, although whether probiotic
      lactobacilli are present or absent in the yogurt does not seem to be a factor in
      this change.

PMID- 18077046
TI  - Shifting pH optimum of Bacillus circulans xylanase based on molecular modeling.
AB  - Although hydrolases are used in several industrial processes, its industrial
      applications have some limitations in specific cases since some industrial
      processes are carried out at pH value which is different from optimum pH of the
      enzyme. Alkaline side optimum pH of hydrolases is always desirable, and it is
      proved difficult to achieve that by mutation only. Hence, molecular modeling was
      applied to select the promising mutants. The changes in electrostatic potential,
      which was calculated using Delphi, were compared to the changes in pH optimum of
      four hydolases and their mutants. The results showed that the change in
      electrostatic potential can be used as an indicator for selecting relevant
      candidates of mutation. Bacillus circulans xylanase was selected as a model
      system, and the promising mutants were picked up by the molecular modeling. Q167M
      and R73V, had a higher pH optimum than the wild type, while K175Q had a similar
      pH-activity profile of the wild type.

PMID- 18077047
TI  - Delivery systems to increase the selectivity of antibiotics in phagocytic cells.
AB  - Many infectious diseases are caused by facultative organisms that are able to
      survive in phagocytic cells. The intracellular location of these microorganisms
      protects them from the host defence systems and from some antibiotics with poor
      penetration into phagocytic cells. One strategy used to improve the penetration
      of antibiotics into phagocytic cells is the use of carrier systems that deliver
      these drugs directly to the target cell. Delivery systems such as liposomes,
      micro/nanoparticles, lipid systems, conjugates, and biological carriers such as
      erythrocyte ghosts may contribute to increasing the therapeutic efficacy of
      antibiotics and antifungal agents in the treatment of infections caused by
      intracellular microorganisms. The main objective of this review is to analyze
      recent advances and current perspectives in the use of antibiotic delivery
      systems in the treatment of intracellular infections such as mycobacterial
      infections, brucellosis, salmonellosis, listeriosis, fungal infections, visceral
      leishmaniasis, and HIV.

PMID- 18077048
TI  - Alanine variant of the Pro12Ala polymorphism of the PPARgamma gene might be
      associated with decreased risk of diabetic retinopathy in type 2 diabetes.
AB  - OBJECTIVE: Molecular background of diabetic retinopathy (DR) remains unknown. An
      interesting group of candidate genes encode proteins involved in insulin
      resistance. AIM: To search for association between the PPARgamma, calpain 10,
      PTPN1 genes and DR in type 2 diabetes mellitus (T2DM). METHODS: We examined 238
      T2DM subjects without DR (NDR) and 121 with DR (mean diabetes duration: 9.1+/-6.8
      and 15.1+/-7.7, respectively). The subjects were genotyped for four markers:
      Pro12Ala of PPARgamma, SNP43 of calpain 10, rs3787345 and rs754118 of PTPN1. The
      distributions of the genotypes were compared using the chi(2)-test and Fisher
      exact test. RESULTS: The alleles and genotypes were not associated with DR in non
      stratified analysis. To investigate the impact of T2DM duration, we performed
      analysis that excluded short duration NDR subjects and long-duration DR subjects.
      It allowed obtaining groups with similar T2DM duration but different DR status
      (DR: 88 individuals, 11.4+/-5.3 years; NDR: 136 individuals, 13.2 years+/-6.2,
      respectively). This analysis suggested that the alanine variant of Pro12Ala might
      be associated with decreased risk of DR (p=0.026 for alleles, p=0.038 and p=0.014
      for genotypes in additive and dominant models, respectively). In multivariable
      logistic regression that included non-genetic parameters, Pro12Ala was not an
      independent risk factor (p=0.28). Further analysis showed, however, that Pro12Ala
      remained significant when urea level was excluded from the model. CONCLUSION: The
      alanine variant of the Pro12Ala polymorphism of PPARgamma might be associated
      with decreased risk of DR in T2DM. This effect may be indirect, at least in part,
      due to diabetic kidney disease.

PMID- 18077050
TI  - The 6th IFAC Symposium on Modelling and Control in Biomedical Systems. Preface.

PMID- 18077049
TI  - Gender modulates the relationship between body weight and plasma glucose in
      overweight or obese subjects.
AB  - Obesity and weight increase during adult life are strong predictors of type 2
      diabetes. Whether fasting plasma glucose (FPG) is likewise related to body weight
      as well as with its increase during the adult life in obese-overweight people and
      whether this relationship is different between the genders is the question asked
      by the present study. We measured FPG in 1063 overweight-obese subjects
      (395M/668F) with BMI > or =25 kgm(-2) and classified with no history of diabetes
      and with a FPG< 7 mmol/l, who consequently came to the Outpatient Clinic of our
      Diabetes Unit to obtain dietetic advice. Weight increase was determined as the
      difference between actual weight and weight at 18 years (weight-diff), including
      only patients with weight-diff> 0. By univariate analysis age, BMI, waist
      circumference and weight change were loosely related to FPG in both sexes, even
      if the relation between plasma glucose and anthropometric variables was more
      consistent in females. By multivariate regression analysis, after adjusting for
      age, waist circumference, menopausal status and smoking habit, FPG was
      significantly related to both waist circumference and weight-diff only in women.
      Odds Ratio for fasting hyperglycaemia (FPG> 6.11 mmol/l), for each S.D. unit
      increase in weight-diff, after adjusting for age, waist circumference, smoking
      habit and menopausal status was 1.272; 95% CI: 0.863-1.901 (p=ns) for males and
      1.800; 95% CI: 1.239-2.652 (p=0.002) for women. In conclusion our findings
      suggest that in non-diabetic overweight-obese people, after controlling for main
      cofounders, anthropometric variables and in particular waist circumference and
      weight change after 18 years are linearly related to FPG in women, independently
      predicting the risk of fasting hyperglycaemia only in these latter.

PMID- 18077051
TI  - Lipid excipients and delivery systems for pharmaceutical development: a
      regulatory perspective.
AB  - The use of lipid-based dosage forms for enhancement of drug absorption or
      delivery has drawn considerable interest from pharmaceutical scientists. The
      unique characteristics of these dosage forms, however, present significant
      challenges to pharmaceutical industry and regulatory agencies in many ways. For
      example, safety assessment is necessary when the use of a new lipid excipient is
      considered. An important question for lipid formulation is whether the drug
      remains in solubilised form along the gastrointestinal (GI) tract after it is
      administered. Certain lipid excipients and surfactants have been reported to
      change intestinal permeability or interfere with enzyme/transporter activity,
      thereby affecting drug bioavailability. The potential influence of
      biopharmaceutical and/or pathophysiological factors on the drug or lipid
      excipient(s) needs to be explored. For a complex lipid-based dosage form, the
      conventional in vitro dissolution methods may not be appropriate for predicting
      in vivo performance in view of the convoluted GI processing of the lipid vehicle
      and formulation Of paramount importance is to identify any gaps in the scientific
      understanding of lipid-based dosage forms so that regulatory issues can be
      addressed. More mechanistic studies should be encouraged to facilitate a better
      understanding of the pharmaceutical characteristics of lipid formulations and
      complex interactions between lipid excipient, drug and physiological environment.
      This review discusses some regulatory considerations in the use of lipid
      excipients and delivery systems for pharmaceutical development. Implications in
      the regulatory determination of pharmaceutical equivalence, bioequivalence and
      therapeutic equivalence are also illustrated.

PMID- 18077052
TI  - Membrane permeable peptide vectors: chemistry and functional design for the
      therapeutic applications.

PMID- 18077053
TI  - Telomere shortening is associated with poor prognosis and telomerase activity
      correlates with DNA repair impairment in non-small cell lung cancer.
AB  - BACKGROUND AND PURPOSE: Telomere function and DNA damage response pathways are
      frequently inactivated in cancer. Moreover, some telomere-binding proteins have
      been implicated in DNA repair. The purpose of this work consists of evaluating
      the prognostic impact of telomere dysfunction and its relationship with DNA
      repair systems in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We
      analysed 83 NSCLCs and their corresponding control samples obtained from patients
      submitted to surgery. Telomere function was evaluated by determining telomerase
      activity and telomere length. DNA repair expression assays were established by
      using cDNA arrays containing 96 DNA-repair genes and by Real Time Quantitative
      PCR. RESULTS: Our data indicated that telomere attrition was significantly
      associated with poor clinical outcome of patients (P=0.02), being this parameter
      a significant prognostic factor independent of tumour stage (P=0.012; relative
      risk=1.887; 95% CI: 1.147-3.102). DNA-repair gene expression studies showed down
      regulation of DCLRE1C and GTF2H1 and a clear FLJ10858 up regulation in tumour
      tissues, as compared to controls. In addition, a number of genes related to DNA
      repair were significantly down regulated in tumours that reactivated telomerase
      (DCLRE1C, GTF2H1, PARP-3, MLH1, and TRF2). CONCLUSIONS: Telomere shortening
      emerged as a poor clinical evolution parameter in NSCLC. Moreover, results from
      this work suggest a relationship between the loss of several DNA repair genes and
      telomerase activity, which may be of relevance in the pathogenesis of non-small
      lung cancer.

PMID- 18077054
TI  - Island rules cannot be broken.

PMID- 18077055
TI  - On the resolution of the lek paradox.
AB  - Directional female mate choice is expected to deplete additive genetic variation
      in male traits. This should preclude such trait-based choice from resulting in
      genetic benefits to offspring, and yet genetic benefits are the explanation for
      the choice. This evolutionary conundrum is known as the lek paradox. Newly
      proposed resolutions to this paradox aim to unravel mechanisms that contribute to
      the persistence of genetic variance in traits under directional female mate
      choice.

PMID- 18077056
TI  - Improved cognitive performance and mental fatigue following a multi-vitamin and
      mineral supplement with added guarana (Paullinia cupana).
AB  - Guarana (Paullinia cupana) extracts are most commonly used in Western markets as
      putatively psychoactive food and drink additives. This double-blind, randomised,
      placebo-controlled, parallel groups study assessed the acute effects of either a
      vitamin/mineral/guarana supplement or placebo drink in 129 healthy young adults
      (18-24 years). Participants completed a 10min version of the Cognitive Demand
      Battery (comprising: Serial 3s and Serial 7s subtraction tasks, a Rapid Visual
      Information Processing (RVIP) task, 'mental fatigue' scale). Thirty minutes
      following their drink participants made six consecutive completions of the
      battery (i.e. 60 min). The vitamin/mineral/guarana combination resulted in
      improved task performance, in comparison to placebo, in terms of both increased
      speed and accuracy of performing the RVIP task throughout the post-dose
      assessment. The increase in mental fatigue associated with extended task
      performance was also attenuated by the supplement. This research supports
      previous findings demonstrating guarana's cognition enhancing properties and
      provides evidence that its addition to a multi-vitamin-mineral supplement can
      improve cognitive performance and reduce the mental fatigue associated with
      sustained mental effort.

PMID- 18077057
TI  - Programmed cell death and differential JNK, p38 and ERK response in a prenatal
      acute hypoxic hypoxia model.
AB  - We previously found that prenatal hypoxia induces a significant increase in the
      levels of active Caspase 3 at 60 min post-hypoxia (p-h) and in the number of
      TUNEL-positive pyknotic cells, which peaks at 6h p-h. The aim of this work was to
      study alterations in MAPKs pathways and the effect of specific inhibitors of the
      JNK (SP600125) and p38 (SB203580) pathways following acute hypoxia in chick optic
      lobe at embryonic day (ED) 12. To this end, JNK, p38 and ERK1-2 protein kinase
      expression levels were determined by Western blot in both their active and
      inactive forms, evaluated at successive p-h times. At 10 and 30 min p-h the P
      JNK/JNK ratio was 1.912+/-0.341 and 1.920+/-0.304, respectively. Concomitantly,
      at 0 min p-h the P-p38/p38 ratio was 1.657+/-0.203. Lastly, the P-ERK/ERK ratio
      proving non-significant throughout. When inhibitors for JNK and p38 were used, we
      observed a decrease in the values of active Caspase 3 at 60 min p-h, which
      correlated with the control values in the parameters of TUNEL-positive cells at
      6h p-h. Analysis for P-ATF-2 demonstrated an increase in hypoxic embryos compared
      to control ones which was reverted in a dose-dependent manner with the use of
      both inhibitors. All these results indicate that at ED 12, acute hypoxia might be
      differentially activating JNK and p38 pathways, without affecting the ERK
      pathway, which in turn would be activating Caspase 3, thus leading to cell death
      by apoptosis. Furthermore, JNK and p38 activation precede in time the programmed
      cell death induced by hypoxia.

PMID- 18077058
TI  - Excitatory synaptic transmission is depressed in cultured hippocampal neurons of
      APP/PS1 mice.
AB  - One of the strongest anatomical correlates of the degree of clinical impairment
      in Alzheimer's disease is a decrease in synaptic density. A detailed
      understanding of the pathophysiological mechanism operating at a synaptic level
      remains incomplete, in particular whether the pre- or the post-synaptic
      compartment is initially involved. Here, we studied synaptic transmission in
      autaptic hippocampal cultures from a double-transgenic mouse model (APPPS1,
      APP(swe) and PS1(L166P)) and a single-mutant APP transgenic model (APP23,
      APPswe). APPPS1 neurons revealed significantly reduced amplitudes of evoked AMPA-
      and NMDA-receptor-mediated excitatory post-synaptic currents, whereas the
      amplitudes of spontaneous miniature synaptic responses were not altered. The size
      of the readily releasable synaptic vesicle pool was also decreased, whereas the
      release probability was not affected. Morphometric immunohistochemical analysis
      showed a reduction in synaptophysin-positive puncta. In contrast, we did not
      identify any alterations in synaptic transmission in neurons derived from single
      APP(swe) transgenic mice. Taken together, our findings suggest that cultured
      neurons of APPPS1 double-transgenic mice have a significantly reduced number of
      functional excitatory synapses.

PMID- 18077059
TI  - Ganglioside GM1 binding the N-terminus of amyloid precursor protein.
AB  - Secreted amyloid precursor protein (APPs) plays a role in several neuronal
      functions, including the promotion of synaptogenesis, neurite outgrowth and
      neuroprotection. Previous study has demonstrated that ganglioside GM1 inhibits
      the secretion of APPs; however the underlying mechanism remains unknown. Here we
      reported that GM1 can bind cellular full length APP and APPs secreted from
      APP(695) stably-transfected SH-SY5Y cells. To characterize the GM1-APP
      interaction further, we expressed and purified recombinant fragments of the N
      terminal APP. Immunoprecipitation experiments revealed that GM1 was able to bind
      the recombinant APP(18-81) fragment. Moreover, the synthetic peptide APP(52-81)
      could inhibit the binding. Therefore, the binding site for GM1 appears to be
      located within residues 52-81 of APP. Furthermore, we found that only GM1, but
      not GD1a, GT1b and ceramide, binds APP-N-terminus, indicating that the specific
      binding depends on the sugar moiety of GM1. Fluorescent studies revealed a
      decrease in the intrinsic fluorescence intensity of the APP(52-81) peptide in
      phosphatidylcholine (PC)/GM1 vesicles. By using FTIR techniques, we found that
      the major secondary structure of the APP(52-81) peptide was altered in PC/GM1
      vesicles. Our results demonstrate that GM1 binds the N-terminus of APP and
      induces a conformational change. These findings suggest that secreted APP is
      decreased by membrane GM1 binding to its precursor protein and provide a possible
      molecular mechanism to explain the involvement of GM1 in APP proteolysis and
      pathogenesis of Alzheimer's disease.

PMID- 18077060
TI  - White matter loss in healthy ageing: a postmortem analysis.
AB  - Age-related brain changes are widely documented. Because of differences in
      measurement methods and case selection, the reported effects of age on regional
      grey and white matter brain volumes, however, are much more pronounced and
      widespread in neuroimaging than in postmortem studies. Consequently, the
      magnitude of the effect that is specific to chronological age remains unresolved.
      We present postmortem volume measurements for 26 cortical, subcortical and white
      matter regions, in 24 human brains aged 46-92 years, free of neuropathological
      abnormalities. Significant age-related loss was observed in anterior and
      posterior white matter but not in total grey matter volumes. Further analyses on
      five cortical subregions previously reported to exhibit large age-related loss on
      MRI yielded negative results. These analyses demonstrate smaller changes with age
      than those reported in imaging studies. Although this discrepancy between
      postmortem and imaging studies may partly be explained by the increase in noise
      of the neuroimaging data with age, our results suggest that healthy brain ageing
      is a process affecting predominantly white matter not grey matter.

PMID- 18077061
TI  - Carotid atherosclerosis and cognitive decline in patients with Alzheimer's
      disease.
AB  - Aim of the study was to explore the correlation between the progression of
      carotid atherosclerosis and the evolution of cognitive impairment in 66 patients
      with Alzheimer's disease (AD). They underwent cognitive status evaluation and
      ultrasonography (US) to investigate carotid arteries intima-media thickness (IMT)
      and plaque index (PI). After a 12-month follow-up period, neuropsychological and
      US examinations were repeated to assess the progression of carotid
      atherosclerosis and of cognitive decline [in terms of changes in Mini Mental
      State Examination (MMSE) scores]. MMSE score changes were related to baseline IMT
      (p=0.018), changes in IMT (p<0.001) and PI (p=0.006), and "antihypertensive drug
      intake" (p<0.001). While the first three variables correlated with increased
      cognitive impairment, the last one was associated with a reduced extent of MMSE
      score decline. Results show a link between progression of carotid wall changes
      and of cognitive decline, and suggest a possible protective role of
      antihypertensive therapy. Given the potential clinical implications, our
      preliminary findings could stimulate further investigations into the role of
      vascular impairment in patients with AD.

PMID- 18077062
TI  - Structural characterisation of the hepatitis C envelope glycoprotein E1
      ectodomain derived from a mammalian and a yeast expression system.
AB  - The structure of the ectodomain of the hepatitis C envelope glycoprotein E1 (E1s)
      was characterised by spectroscopic methods. Monomeric E1s was purified from a
      mammalian and from a Hansenula polymorpha cell lysate, and cysteine-blocked
      monomers were reconstituted into stable particles. Particles from yeast E1s and
      mammalian E1s showed a comparable reactivity in ELISA with sera from human
      chronic HCV carriers, similar antibody titers in the sera of immunised mice as
      well as a comparable structure as analyzed by spectroscopic methods (tryptophan
      fluorescence, circular dichroism, and Fourier transform infrared spectroscopy).
      The overall secondary structure of E1s was neither influenced by the degree of
      glycosylation nor by the nature of cysteine modification used during
      purification. The structural comparability of mammalian- and H. polymorpha
      expressed E1s opens new perspectives for further development of E1s-based
      therapeutics as yeast systems generally allow a more easy scaling up.

PMID- 18077064
TI  - "Study of pain and swelling after oral mucosal biopsy".
AB  - We studied the incidence and severity of pain and swelling during the 7 days
      after biopsy of the oral mucosa. A visual analogue scale (VAS) was used to assess
      postoperative pain and swelling in 84 patients with lesions that were amenable to
      histopathological study, in whom the oral mucosa was biopsied under local
      anaesthesia, after informed consent was obtained. The data were analysed using a
      non-parametric ranking test. Maximum pain intensity was recorded after two hours,
      while swelling peaked between 6-48 hours after biopsy. Pain after two hours was
      greater among women than men (median 2.0 (0-8.5) compared with 0.4 (0-8.0),
      p=0.010) and in lesions of the floor of the mouth (2.4 (0-4.3)), but the latter
      was not significant. Swelling between 6 and 48 hours after biopsy was also more
      in women than men (p=0.002), and in lesions of the lip (4.2 (0-10)), p<0.001
      compared with cheek, p=0.002 compared with gums and p=0.001 compared with palate.
      We recorded maximum pain and swelling after biopsy of the oral mucosa during the
      first 48 hours, after which it gradually reduced.

PMID- 18077063
TI  - Clonal vaccinia virus grown in cell culture fully protects monkeys from lethal
      monkeypox challenge.
AB  - The potential use of smallpox as an agent of bioterrorism has renewed interest in
      the development of a modern vaccine capable of replacing the standard Dryvax
      vaccine. Vaccinia virus (ACAM2000), clonally isolated from Dryvax and
      manufactured in cell culture, was tested for immunogenicity and protective
      activity in a non-human primate model. Cynomolgus monkeys vaccinated with
      ACAM2000, Dryvax, or ACAM2000 diluent (control) were challenged 2 months post
      vaccination with a lethal, intravenous dose of monkeypox virus. ACAM2000 proved
      immunogenic and efficacious in protecting against lethal monkeypox challenge, as
      evident from a lack of post-challenge viral replication, and the absence of any
      significant clinical signs attributable to monkeypox infection. This protection
      correlated (with) neutralizing antibody titers equivalent to those generated in
      the Dryvax group post-vaccination, as well as a similar significant increase in
      the presence of neutralizing antibodies post-challenge. Control animals showed no
      signs of vaccine-induced seroconversion, displayed post-challenge tissue
      associated viral replication and viremia, and developed severe monkeypox-specific
      clinical symptoms. The protective efficacy of ACAM2000 was found to be equivalent
      to the currently approved vaccine, Dryvax.

PMID- 18077065
TI  - Mechanical efficiency and propulsion technique after 7 weeks of low-intensity
      wheelchair training.
AB  - BACKGROUND: To evaluate the effect of a 7-week low-intensity hand rim wheelchair
      training on the submaximal metabolic cost, mechanical efficiency and propulsion
      technique in able-bodied participants. METHODS: Participants were randomly
      divided over an experimental group (n=14) and a control group (n=7). The
      experimental group received 7 weeks wheelchair training (3 week(-1), 70 min) at a
      low intensity (30% of the heart rate reserve), whereas the control group did not
      receive training. During pre- and post-tests, submaximal exercise was performed
      on a stationary wheelchair ergometer at fixed levels of power output. Mechanical
      efficiency, oxygen uptake, heart rate, timing parameters and stroke angles were
      measured. Video recordings were made to determine the stroke pattern. FINDINGS:
      Mechanical efficiency increased and metabolic cost decreased significantly in the
      experimental group compared to the control group. Push time increased and cycle
      frequency decreased as a result of training. The stroke angle increased in the
      experimental group during the training period. The experimental group preferred
      double-looping over propulsion, while the control group mainly used single
      looping over propulsion patterns during the post-test. INTERPRETATION: A low
      intensity, 7-week training protocol has a beneficial effect on the mechanical
      efficiency and metabolic cost of wheelchair propulsion in able-bodied
      participants. The improved mechanical efficiency seems to be the result of
      changes in propulsion technique that were found.

PMID- 18077066
TI  - Development and specification of physiologically based pharmacokinetic models for
      use in risk assessment.
AB  - Risk assessments are performed to estimate the conditions under which individuals
      or populations may be harmed by exposure to environmental or occupational
      chemicals. In the absence of quantitative data in the human, this process is
      often dependent upon the use of animal and in vitro data to estimate human
      response. To reduce the uncertainty inherent in such extrapolations, there has
      been considerable interest in the development of physiologically based
      pharmacokinetic (PBPK) models of toxic chemicals for application in quantitative
      risk assessments. PBPK models are effective tools for integrating diverse dose
      response and mechanistic data in order to more accurately predict human risk.
      Yet, for these models to be useful and trustworthy in performing the necessary
      extrapolations (species, doses, exposure scenarios), they must be thoughtfully
      constructed in accordance with known biology and pharmacokinetics, documented in
      a form that is transparent to risk assessors, and shown to be robust using
      diverse and appropriate data. This paper describes the process of PBPK model
      development and highlights issues related to the specification of model structure
      and parameters, model evaluation, and consideration of uncertainty. Examples are
      provided to illustrate approaches for selecting a "preferred" model from multiple
      alternatives.

PMID- 18077067
TI  - Automatic imitation of intransitive actions.
AB  - Previous research has indicated a potential discontinuity between monkey and
      human ventral premotor-parietal mirror systems, namely that monkey mirror systems
      process only transitive (object-directed) actions, whereas human mirror systems
      may also process intransitive (non-object-directed) actions. The present study
      investigated this discontinuity by seeking evidence of automatic imitation of
      intransitive actions--hand opening and closing--in humans using a simple reaction
      time (RT), stimulus-response compatibility paradigm. Left-right and up-down
      spatial compatibility were controlled by ensuring that stimuli were presented and
      responses executed in orthogonal planes, and automatic imitation was isolated
      from simple and complex orthogonal spatial compatibility by varying the
      anatomical identity of the stimulus hand and response hemispace, respectively. In
      all conditions, action compatible responding was faster than action incompatible
      responding, and no effects of spatial compatibility were observed. This
      experiment therefore provides evidence of automatic imitation of intransitive
      actions, and support for the hypothesis that human and monkey mirror systems
      differ with respect to the processing of intransitive actions.

PMID- 18077068
TI  - Prevalence of depressive and anxiety disorders in systemic lupus erythematosus
      and their association with anti-ribosomal P antibodies.
AB  - OBJECTIVE: To estimate the prevalence of psychiatric disorders in patients with
      systemic lupus erythematosus (SLE) and explore their association with anti
      ribosomal P (anti-P) antibodies. METHODS: Seventy-one consecutive female SLE
      patients without neurological manifestations were evaluated for psychiatric
      disorders using the Structured Clinical Interview for DSM-IV (SCID). Anti-P
      antibodies were measured by enzyme-linked immunosorbent assay (ELISA)/immunoblot
      analysis. RESULTS: The mean age of subjects was 34.8 years (SD: 10.1 years), and
      the mean duration of SLE was 9.8 years (SD: 6.5 years). The 30-day prevalences of
      psychiatric disorders were: mood disorders 26.8%, anxiety disorders 46.5%,
      adjustment disorders 8.4%, alcohol abuse 1.4%, and somatoform disorder 1.4%. The
      lifetime prevalences of psychiatric disorders were: mood disorders 69%, anxiety
      disorders 52.1%, alcohol abuse 1.4%, and somatoform disorder 1.4%. Subjects with
      and without psychiatric manifestations did not differ regarding SLE clinical and
      laboratorial parameters including presence or absence of anti-P antibodies (23.1%
      vs. 20%, respectively, p=1.0), disease activity, as measured by the Systemic
      Lupus Erythematosus Disease activity Index (4.08+/-5.7 vs. 4.95+/-6.3
      respectively, p=0.60) and cumulated damage, as measured by the Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology Damage Index
      (0.7+/-2.3 vs. 0.3+/-0.7 respectively, p=0.33). CONCLUSIONS: Mood and anxiety
      disorders are the most frequently observed psychiatric disorders in female SLE
      patients without concomitant neurological manifestations. These mild/moderate
      forms of psychiatric disorders are not associated with anti-P antibodies in SLE
      patients. Our findings reinforce the importance of systematic psychiatric
      evaluation for these patients in order to provide adequate and comprehensive
      care.

PMID- 18077069
TI  - Acute stress differentially affects corticotropin-releasing hormone mRNA
      expression in the central amygdala of the "depressed" flinders sensitive line and
      the control flinders resistant line rats.
AB  - Preclinical and clinical evidence suggests that neuropeptides play a role in the
      pathophysiology of mood disorders. In the present study, we investigated the
      involvement of the peptides corticotropin-releasing hormone (CRH), neuropeptide Y
      (NPY) and nociceptin/orphanin FQ (N/OFQ) and of their receptors in the regulation
      of emotional behaviours. In situ hybridization experiments were performed in
      order to evaluate the mRNA expression levels of these neuropeptidergic systems in
      limbic and limbic-related brain regions of the Flinders Sensitive Line (FSL)
      rats, a putative genetic animal model of depression. The FSL and their controls,
      the Flinders Resistant Line (FRL) rats, were subjected to one hour acute
      restraint and the effects of the stress exposure, including possible strain
      specific changes on these neuropeptidergic systems, were studied. In basal
      conditions, no significant differences between FSL and FRL rats in the CRH mRNA
      expression were found, however an upregulation of the CRH mRNA hybridization
      signal was detected in the central amygdala of the stressed FRL, compared to the
      non stressed FRL rats, but not in the FSL, suggesting a hypoactive mechanism of
      response to stressful stimuli in the "depressed" FSL rats. Baseline levels of NPY
      and N/OFQ mRNA were lower in the FSL rats compared to the FRL in the dentate
      gyrus of hippocampus and in the medial amygdala, respectively. However, the
      exposure to stress induced a significant upregulation of the N/OFQ mRNA levels in
      the paraventricular thalamic nucleus, while in the same nucleus the N/OFQ
      receptor mRNA expression was higher in the FSL rats. In conclusion, selective
      alterations of the NPY and N/OFQ mRNA in limbic and limbic-related regions of the
      FSL rats, a putative animal model of depression, provide further support for the
      involvement of these neuropeptides in depressive disorders. Moreover, the lack of
      CRH activation following stress in the "depressed" FSL rats suggests a form of
      allostatic load, that could alter their interpretation of environmental stimuli
      and influence their behavioural response to stressful situations.

PMID- 18077070
TI  - Serotonin syndrome associated with sertraline monotherapy at therapeutic doses.

PMID- 18077072
TI  - Myelin glycoproteins targeted by lead in the rodent model of prolonged exposure.
AB  - The aim of these experiments was to discern whether prolonged exposure of rats to
      lead (Pb) in water, as occurs in typical environmental exposure, affects the
      structure of myelin in the brain, the protein levels of the myelin glycoproteins
      myelin associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein
      (MOG). During chronic lead intoxication, Pb levels in myelin fractions
      significantly increases. Prolonged lead exposure was found to decrease the
      expression of both MAG and MOG to a similar degree (80-85% of control values).
      Additionally, the electron microscopic studies have indicated the existence of
      structural changes in the axonal myelin sheath by revealing disintegration of its
      multilamellar structure. These morphological disturbances in Pb-intoxicated rats
      were paralleled by changes in myelin membrane fluidity as measured by
      spectrofluorometry and electron paramagnetic resonance (EPR) techniques employing
      a fatty acid spin label. In Pb-treated rats, enhanced membrane fluidity was
      observed, as indicated both by decreased anisotropy of the membrane and decreased
      order parameter. These results suggest that Pb influences the integrity of the
      myelin sheath in brain of adult rats and decreased level of both glycoproteins
      may significantly contribute to that effect.

PMID- 18077073
TI  - Carcinogenicity and chronic toxicity of di-2-ethylhexyl terephthalate (DEHT)
      following a 2-year dietary exposure in Fischer 344 rats.
AB  - The carcinogenicity and chronic toxicity potential of di-2-ethylhexyl
      terephthalate (DEHT) was assessed in F-344 rats (50/sex/dose) by dietary exposure
      for 104 weeks. Exposure levels of 0, 1500, 6000 or 12,000 ppm resulted in average
      daily doses of 79, 324 and 666 mg/kg/day for males and 102, 418 and 901 mg/kg/day
      for females. Animals were observed daily for clinical signs and detailed physical
      examinations were performed weekly. Body weight and food consumption were
      measured at scheduled intervals. During weeks 103-104, urine and blood samples
      were collected and analyzed. Eyes were examined during week 104 using a binocular
      indirect ophthalmoscope. At necropsy, organs were weighed and examined
      macroscopically and microscopically. No histological effects were noted in any
      organ at any dose and there was no increase in the incidence of any tumor types.
      Toxic responses were confined to lower weight gains and food conversion
      efficiency in males and females ingesting 6000 or 12,000 ppm. The severity of a
      normal geriatric degenerative retinal change was exacerbated in females exposed
      to 6000 or 12,000 ppm and in males exposed to 12,000 ppm. Therefore, the no
      observed effect level (NOEL) for tumorigenicity was 12,000 ppm and the NOEL for
      chronic toxicity was 1500 ppm.

PMID- 18077074
TI  - [Post-treatment sequelae after breast cancer conservative surgery].
AB  - Thanks to the earlier detection of breast cancer, the advent of neoadjuvant
      therapy and the development of more effective surgical procedures reducing
      treatment sequelae, conservative treatment has dramatically expanded over the
      past 15 years. Several factors have recognized negative aesthetic consequences
      for breast cancer patients: being overweight, having voluminous or on the
      contrary, very small breasts, having a tumor located in the lower quadrant,
      having high breast-tumor: breast-volume ratio. Tissue injuries induced by
      radiotherapy and chemotherapy, such as shrinking, fibrosis or induration,
      maximize the deleterious impact of surgery. The results of conservative treatment
      also deteriorate with time: weight gain is common and may result in increased
      breast asymmetry. Patients undergoing conservative treatment may experience
      sequelae including various degrees of the following dimorphisms, all possibly
      responsible for minor or even major breast deformity: breast asymmetry, loss of
      the nipple/areola complex, scar shrinkage and skin impairment, irregular shape
      and position of the nipple and areola. Various sensory symptoms have also been
      reported following conservative treatment, with patients complaining of hypo- or
      dysesthesia or even suffering actual pain. Breast lymphedema is also a common
      incapacitating after-effect that is believed to be largely underdiagnosed in
      clinical practice. Finally, like mastectomy, conservative breast surgery may
      induce serious psychological distress in patients who suffer the loss of physical
      integrity, womanhood or sexual arousal. Clinicians must be aware of the
      radiological changes indicative of late cancer recurrence. There are four types
      of modifications as follows: increased breast density, architectural distortion
      at the surgical site and formation of scar, mammary fat necrosis, and occurrence
      of microcalcifications. The management of sequelae of conservative breast
      treatment must therefore involve a multidisciplinary approach; patients not only
      expect better cosmetic appearance, but also a focus on other treatment advances
      such as improvement of psychological and sensory outcome. The interpretation of
      radiological images is also an integral part of the management of these patients
      at significant risk of recurrence.

PMID- 18077075
TI  - Effects of long-term low-dose cadmium exposure on genomic DNA methylation in
      human embryo lung fibroblast cells.
AB  - Cadmium is a toxic transition metal of continuing occupational and environmental
      concern. As a well-recognized human carcinogen, its carcinogenic mechanisms are
      still poorly understood. Cadmium has long been considered a non-genotoxic
      carcinogen and thought to act through epigenetic mechanisms. In the present
      study, we tested the effects of long-term low-dose cadmium exposure on DNA
      methylation in human embryo lung fibroblast (HLF) cells. After 2 months of
      exposure to 0-1.5 micromol/L cadmium, both the level of genomic DNA methylation
      and the enzyme activity of DNA methyltransferases (DNMTs) were increased in a
      concentration-related manner. Moreover, our results showed that cadmium exposure
      up-regulated the mRNA levels of DNMT1, DNMT3a and DNMT3b at higher
      concentrations. We further tested the growth dynamics of HLF cells, and observed
      significantly elevated growth rates, decreased cell population of G0/G1-phase and
      increased cell population of S-phase at 0.9, 1.2, and 1.5 micromol/L
      concentrations. Our study indicated that long-term low-dose cadmium exposure
      could disrupt DNA methylation, which may be one of the possible underlying
      carcinogenic mechanisms of cadmium.

PMID- 18077077
TI  - Molecular mechanisms triggered by mercury.
AB  - Mercury is an ubiquitous environmental toxin that causes a wide range of adverse
      health effects in humans. Three forms of mercury exist: elemental, inorganic and
      organic. Each of them has its own profile of toxicity. Exposure to mercury
      typically occurs by inhalation or ingestion. Mercury can be an indoor air
      pollutant, however industry emission remains the most important source of inhaled
      mercury. Furthermore, fresh water and ocean fish may contain large amounts of
      mercury and dental amalgam can be another important source of inorganic and
      mercury vapor. The present review discusses the current information on mercury
      toxicity and the distinct toxicologic profile of the three forms of mercury. The
      existing therapeutics, new therapeutics development or agents for treating
      mercury poisoning will also discussed. Since in general low levels of mercurial
      are tolerable, herein, we also discuss the defensive mechanisms developed by the
      cell to protect itself against mercury injury. This aspect may be useful to
      provide a biological protection against toxic effects exerted by mercury or by
      specific forms of mercury in view of a medicinal purposes.

PMID- 18077078
TI  - Repeated experiences of air hunger and ventilatory behavior in response to
      hypercapnia in the standardized rebreathing test: effects of anxiety.
AB  - In this study, we assessed air hunger (AH) and ventilatory responses to repeated
      CO(2) exposures in healthy women (N=31), scoring high or low for trait anxiety. A
      standardized rebreathing test, implying a gradually increasing CO(2) stimulus,
      was administered three times with 15-min intervals. Respiratory behavior and the
      intensity of AH perception were measured continuously. Across repeated exposures,
      maximal tolerance for AH habituated and the slope of AH (increase in AH per unit
      increase in CO(2)) diminished. Also the dynamics of the breathing response
      changed across trials. The thresholds for AH and tidal volume (V(T)) moved closer
      to each other, whereas the threshold for the respiratory rate (RR) was generally
      postponed. In addition, the association between AH and V(T) was stronger than
      between AH and RR, and the latter association became weaker over trials,
      particularly in high anxious persons. This suggests that AH perception became
      increasingly influenced by psychological factors, especially in high anxious
      persons. The results suggest that habituation of perceived air hunger is
      depending on a complex interplay between both changes in respiratory behavior and
      in perceptual-cognitive processes related to trait anxiety.

PMID- 18077076
TI  - Examination of mRNA expression in rat hearts and lungs for analysis of effects of
      exposure to concentrated ambient particles on cardiovascular function.
AB  - Epidemiological studies have suggested that fine particulate matter (f-PM) is
      associated with adverse effects on cardiovascular health. However, these effects
      on the cardiovascular system have not yet been fully elucidated. Using mRNA
      expression and correlation analyses, we designed the present study to elucidate
      (1) translocation of chemicals in inhaled f-PM to the heart, (2) induction of
      oxidative stress, one of the causes of cardiovascular diseases (CVDs), (3) mRNA
      expression related to CVDs, and (4) correlations among mRNA expression of various
      molecules and cardiovascular function. Wistar Kyoto male rats were exposed to
      concentrated ambient particles (CAPs, 0.6-1.5mg/m3) in Yokohama for 4 days
      (4.5h/day) or to filtered air for 3 days and CAPs for 1 day or to filtered air
      for 4 days. Messenger RNA expression and cardiovascular function were measured
      after the 4-day exposure. In samples of heart tissue, the mRNAs of cytochrome
      P450 (CYP) 1B1, a biomarker of exposure to chemicals; heme oxygenase-1 (HO-1), a
      marker of oxidative stress; and endothelin A (ET A) receptor, a receptor of
      vasoconstrictors, were up-regulated by CAPs; their levels were significantly
      correlated with the cumulative weight of CAPs in the exposure chamber. The up
      regulation of ET A receptor mRNA was significantly correlated with the increase
      in HO-1 mRNA and weakly with the increase in mean blood pressure (Delta MBP).
      These results suggest the possibility that chemicals in CAPs might be
      translocated to the heart, where they induce oxidative stress and activate
      endothelin signaling, resulting in an increase in the blood pressure. The
      exposure to f-PM might thus affect cardiovascular function through activation of
      endothelin signaling.

PMID- 18077079
TI  - Efficient water use in industries: cases from the Indian agro-based pulp and
      paper mills.
AB  - Agro-based pulp and paper mills in India are one of the most polluting
      industries; in addition, they are high consumers of raw water. Growing scarcity
      of high quality freshwater as well as stringent regulatory standards is
      compelling these units to explore appropriate water management options. Based on
      data obtained through a questionnaire survey and plant visits, this work provides
      an overview of the water use and effluent treatment status in Indian agro-residue
      and recycled pulp and paper mills. The challenges faced by this sector are
      reviewed and practices adopted by progressive units to minimize freshwater use
      are illustrated through case studies.

PMID- 18077080
TI  - Nonspherical vibrations of microbubbles in contact with a wall: a pilot study at
      low mechanical index.
AB  - Radially oscillating microbubbles can deform when in contact with a wall. These
      nonspherical shapes have a preferential orientation perpendicular to the wall.
      Conventional microscope setups for microbubble studies have their optical axis
      perpendicular to the wall (top view); consequently they have a limited view of
      the deformation of the bubble. We developed a method to image the bubble in a
      side view by integrating a mirror in the microscope setup. The image was recorded
      at 14.5 million frames per second by a high-speed camera. When insonified by a 1
      MHz, 140-kPa ultrasound pulse, a 9-microm diameter coated bubble appeared
      spherical in the top view, but strongly nonspherical in the side view. Its shape
      was alternatively oblate and prolate, with maximum second order spherical
      harmonic amplitude equal to the radius.

PMID- 18077081
TI  - Development of integrated backscatter intravascular ultrasound for tissue
      characterization of coronary plaques.
AB  - Tissue characterization of plaques of coronary arteries is important to clarify
      the process of acute coronary syndrome and prevent it. The purpose of this study
      is to develop an online integrated backscatter intravascular ultrasound (IB-IVUS)
      system and validate the diagnostic accuracy for the characterization of coronary
      plaques. A personal computer equipped with custom software was connected to an
      IVUS imaging system. Images were acquired from 242 segments of 46 coronary
      arteries from 25 cadavers obtained at autopsy. In the training study, a total of
      724 regions-of-interests on color-coded maps were compared with histologic
      images. In the validation study, a total of 192 cross-sections of coronary
      arteries were evaluated. Receiver operating characteristic curve analysis showed
      that the cut-off points of -49 dB (area under curve = 0.98) and -29 dB (area
      under curve = 0.99) were the most reliable predictors of lipid pools, fibrosis
      and calcification. In the validation study, the analysis using IB values
      classified fibrous, lipid-rich and fibrocalcific plaque components with a high
      accuracy of 93%, 90% and 96%, respectively. The overall agreement between
      histologic and IB-IVUS diagnoses (n = 175) was high (Cohen's kappa = 0.81). The
      IB-IVUS system provides high diagnostic accuracy for analysis of tissue
      characteristics of coronary plaques.

PMID- 18077082
TI  - High frequency ultrasound device to investigate the acoustic properties of whole
      blood during coagulation.
AB  - This study was designed to investigate the changes in acoustic properties of
      whole blood during the coagulation process. High frequency (from 20 to 40 MHz)
      ultrasound parameters were measured both in double transmission (DT) and
      backscattering (BS) mode to assess sound velocity and backscatter coefficient,
      respectively. The integrated backscatter coefficient (IBC) and the effective
      scatterer size (ESS) were deducted from the backscatter coefficient. Measurements
      were performed on whole blood samples collected from 12 healthy volunteers.
      During the blood clotting process (2 h observation), acoustic parameters were
      measured with 15 s time resolution for the transmission parameter and 5 s (for
      the 5 first min) and 30 s (for the end of the observation time) for the
      backscattering parameters. The results obtained clearly showed that simultaneous
      measurements of parameters in DT and BS modes are able to identify several stages
      during the in vitro blood clotting process. In particular, red blood cell (RBC)
      aggregation can be described from the backscattering parameters and liquid-gel
      transition phase of blood from the sound velocity. Intra- and inter-individual
      dispersion of these parameters were also measured and discussed.

PMID- 18077083
TI  - Germline alterations in the CLSPN gene in breast cancer families.
AB  - About 5-10% of breast cancer is thought to be due to an inherited disease
      predisposition. Currently known genes account for less than half of the
      hereditary cases. Claspin, a tumor suppressor protein encoded by the CLSPN gene,
      is involved in monitoring of replication and sensoring of DNA damage and
      cooperates with CHK1 and BRCA1. Association with certain cell proliferation
      stimulatory features has also been described. Many previously identified
      susceptibility factors act in similar functional pathways as claspin, suggesting
      possible involvement of CLSPN in heritable breast cancer susceptibility. Here we
      have screened affected index cases from 125 Finnish cancer families for germline
      defects in CLSPN using conformation sensitive gel electrophoresis (CSGE) and
      direct sequencing. Altogether seven different sequence changes were observed, but
      none of them appeared to associate with breast cancer susceptibility. To our
      knowledge, this is the first study reporting the mutation screening of the CLSPN
      gene in familial breast cancer cases.

PMID- 18077084
TI  - Effective induction of anti-tumor immune responses with oligomannose-coated
      liposome targeting to intraperitoneal phagocytic cells.
AB  - We recently established a novel drug delivery system (DDS) using oligomannose
      coated liposomes (OMLs) which are probably taken up by macrophages (Mvarphi) to
      carry anti-cancer drugs to milky spots known as preferential metastatic sites of
      gastric cancers [Y. Ikehara, T. Niwa, L. Biao, S.K. Ikehara, N. Ohashi, T.
      Kobayashi, Y. Shimizu, N. Kojima, H. Nakanishi, A carbohydrate recognition-based
      drug delivery and controlled release system using intraperitoneal macrophages as
      a cellular vehicle, Cancer Res. 66 (2006) 8740-8748]. In the present study, we
      applied this intraperitoneal DDS for systemic cancer immunotherapy employing
      ovalbumin (OVA) as a model antigen. The cells taking up the OMLs containing FITC
      OVA injected into the peritoneal cavity were predominantly Mvarphi, as they
      showed adhesive characteristics and expressed F4/80 and CD11b almost exclusively.
      The phagocytic cells also took up bare OVA directly to the same extent as OML
      enclosed OVA (OML-OVA), as it is a highly mannosilated protein. The phagocytic
      cells taking up OML-OVA, however, could activate OVA-specific CD8+ (from OT-I: H
      2Kb/OVA257-264-specific) and CD4+ (from OT-II: H-2Ab/OVA323-339-specific) T cells
      much more effectively in vitro than those taking up bare OVA. Furthermore, only
      the mice pre-immunized with OML-OVA rejected E.G7-OVA (OVA-transfected EL4) but
      not EL4. These results indicate that the OMLs can also be used as an effective
      antigen delivery system for cancer immunotherapy activating both CTL and Th
      subsets.

PMID- 18077085
TI  - Microemulsion-mediated hydrothermal synthesis of photocatalytic TiO2 powders.
AB  - A reverse microemulsion-mediated hydrothermal route has been employed to
      synthesize photocatalytic titanium dioxide (TiO2) powders. Nano-crystalline
      monophasic anatase TiO2 powders were successfully prepared when the microemulsion
      derived precursors were hydrothermally treated. The advantage of using this
      microemulsion mediated hydrothermal route is the significant reduction in
      reaction time and temperatures as compared with the conventional hydrothermal
      process. The oil/water emulsion ratio significantly affected the particle sizes
      of the obtained TiO2 powders. The specific surface area of TiO2 powders was
      increased with the oil/water ratio, thereby leading to enhanced photocatalytic
      activity of TiO2 powders. As the hydrothermal temperature was elevated, the
      morphology of the TiO2 particles changed from a rod-like shape into a polyhedral
      shape. The variation in microstructures decreased the specific surface area of
      the TiO2 powders and lowered the photocatalytic activity.

PMID- 18077086
TI  - Thermal treatment and vitrification of boiler ash from a municipal solid waste
      incinerator.
AB  - Boiler ash generated from municipal solid waste (MSW) incinerators is usually
      classified as hazardous materials and requires special disposal. In the present
      study, the boiler ash was characterized for the chemical compositions, morphology
      and microstructure. The thermal chemical behavior during ash heating was
      investigated with thermal balance. Vitrification of the ash was conducted at a
      temperature of 1400 degrees C in order to generate a stable silicate slag, and
      the formed slag was examined with chemical and mineralogical analyses. The effect
      of vitrification on the leaching characteristics of various elements in the ash
      was evaluated with acid leaching. The study shows that the boiler ash as a
      heterogeneous fine powder contains mainly silicate, carbonate, sulfates,
      chlorides, and residues of organic materials and heavy metal compounds. At
      elevated temperatures, the boiler ash goes through the initial moisture removal,
      volatilization, decomposition, sintering, melting, and slag formation. At 1400
      degrees C a thin layer of salt melt and a homogeneous glassy slag was formed. The
      experimental results indicate that leaching values of the vitrified slag are
      significantly reduced compared to the original boiler ash, and the vitrification
      could be an interesting alternative for a safer disposal of the boiler ash. Ash
      compacting, e.g., pelletizing can reduce volatilization and weight loss by about
      50%, and would be a good option for the feed preparation before vitrification.

PMID- 18077087
TI  - Robotic swarm concept for efficient oil spill confrontation.
AB  - This paper examines the behaviour of a distributed system/robotic swarm concept
      for the effective confrontation of oil spills. The system described consists of a
      number of identical robotic units of high-power autonomy that recover oil
      mechanically and are able to communicate with each other. A mathematical model
      that accounts for a multitude of oil weathering processes and for the concerted
      action of the autonomous units is implemented for this investigation.
      Computational assessment of the robotic swarm in weathering oil spills indicates
      the potential effectiveness of the method.

PMID- 18077088
TI  - Effect of cadmium toxicity on nitrogen metabolism in leaves of Solanum nigrum L.
      as a newly found cadmium hyperaccumulator.
AB  - Hyperaccumulators are ideal plant species used for phytoremediation of soils
      contaminated by heavy metals. A full understanding of metal tolerance mechanisms
      of hyperaccumulators will facilitate enhancing their phytoremediation efficiency.
      However, how Cd affects N metabolism and which role plays the response of N
      metabolism to Cd toxicity in the tolerance of hyperaccumulators are still
      unknown. To clarify these questions, this study investigated the effects of
      various soil Cd levels on the concentrations of N forms and the activity of key
      enzymes involved in N metabolism in leaves of the Cd hyperaccumulator, Solanum
      nigrum L. The results showed that its growth and all N metabolism indicators were
      normal at low Cd exposure (<or=12 mg kg(-1)). At 24 mg Cd kg(-1) soil, nitrate
      assimilation indicators (nitrate concentration and activity of nitrate reductase)
      were reduced significantly, whereas most ammonia assimilation indicators
      (ammonium concentration and activity of glutamine synthetase) remained normal.
      However, when exposed to a higher Cd level (48 mg kg(-1)), growth and most N
      metabolism indicators were reduced significantly. Therefore, N metabolism in
      leaves of S. nigrum could be tolerant of Cd toxicity to a certain extent (soil Cd
      concentration<or=12 mg kg(-1)), and this might be involved in the Cd-tolerance of
      this Cd-hyperaccumulator.

PMID- 18077089
TI  - Kinetics of the biodegradation of green table olive wastewaters by aerobic and
      anaerobic treatments.
AB  - The biodegradation of the organic pollutant matter present in green table olive
      wastewater (GTOW) is studied in batch reactors by an aerobic biodegradation and
      by an anaerobic digestion. In the aerobic biodegradation, the evolution of the
      substrate (in terms of chemical and biochemical oxygen demand), biomass, and
      total polyphenolic compounds present in the wastewater are followed during the
      process, and a kinetic study is performed using Contois' model, which when
      applied to the experimental results provides the kinetic parameter of this model,
      resulting in a modified Contois' equation (q=3.3S/(0.31S(0)X+X), gCOD/gVSS d(
      1)). Other kinetic parameters were determined: the cellular yield coefficient
      (YX/S=5.7x10(-2) gVSS/gCOD) and the kinetic constant of cellular death phase
      (kd=0.16 d(-1)). Similarly, in the anaerobic digestion, the evolution of the
      substrate digested and the methane produced are followed, and the kinetic study
      is conducted using a modified Monod model combined with the Levenspiel model, due
      to the presence of inhibition effects. This model leads to the determination of
      the kinetic parameters: kinetic constant when no inhibitory substance is present
      (kM0=8.4x10(-2) h(-1)), critical substrate concentration of inhibition (TP*=0.34
      g/L) and inhibitory parameter (n=2.25).

PMID- 18077090
TI  - Studies on three-dimensional coordination polymer [Cd2(N2H4)2(N3)4]n: crystal
      structure, thermal decomposition mechanism and explosive properties.
AB  - A 3D coordination polymer of cadmium(II) hydrazine azide, [Cd2(N2H4)2(N3)4]n, was
      synthesized and characterized by elemental analysis and Fourier transform
      infrared (FT-IR) spectrum. Its crystal structure was determined by single crystal
      X-ray diffraction analysis. The crystal belongs to monoclinic, P2(1)/c space
      group, a=12.555(2)A, b=11.724(2)A, c=7.842(1)A, beta=94.56(2) degrees and Z=4.
      The crystal contains two crystallographically independent sets of distorted
      octahedral Cd(II) atoms and dimeric units of Cd2N2, Cd2(NNN)2, Cd2(NN)2 through
      double micro-1, 1 azide bridges, micro-1, 3 azide bridges and bidentate bridging
      hydrazine ligands, respectively, and thus generating a 3D network structure. The
      thermal decomposition mechanism of the complex was studied by using differential
      scanning calorimetry (DSC), thermogravimetry-derivative thermogravimetry (TG-DTG)
      and FT-IR techniques. Under nitrogen atmosphere with a heating rate of 10 degrees
      C/min, the thermal decomposition of the complex contained two intense exothermic
      decomposition processes in the range of 150-304 degrees C in the DSC curve, and
      the final decomposed residue at 500 degrees C was Cd. Sensitivity tests revealed
      that the title complex is very insensitive to external stimuli.

PMID- 18077092
TI  - Localized or widespread musculoskeletal pain: does it matter?
AB  - Although epidemiological descriptions indicate that musculoskeletal pain is often
      widespread, still a lot of musculoskeletal pain is diagnosed and treated as
      localized pain. This led us to question whether localized pain exists at all and
      to evaluate its functional impact compared with that of widespread
      musculoskeletal pain. Therefore, this study aimed to describe the prevalence of
      localized and widespread musculoskeletal pain and its association to functional
      ability. In 2004, questionnaires about musculoskeletal pain were mailed to seven
      age groups in Ullensaker, Norway: 24-26, 34-36, 44-46, 54-56, 64-66, 74-76, and
      84-86 years old. In total, 3325 persons participated (participation rate 54.4%).
      We excluded the oldest age group and persons who did not respond to any questions
      about pain during the previous week, thus reducing the participants in this study
      to 3179. Although musculoskeletal pain occurred frequently in the population,
      localized pain, in the meaning of single site pain, was relatively rare. Most
      people having musculoskeletal pain reported pain from a number of sites.
      Furthermore, experiencing single site pain did not have a large impact on
      physical fitness, feelings, or daily and social activities. Functional problems
      increased markedly, in an almost linear way with increasing number of pain sites.
      These findings suggest that musculoskeletal pain usually coexists with pain in
      other body regions and that the functional consequences are highly dependent on
      how widespread the pain is. This should have important implications for future
      research into musculoskeletal pain, and for clinical and social insurance
      medicine.

PMID- 18077091
TI  - CSF histamine levels in rats reflect the central histamine neurotransmission.
AB  - Reduced cerebrospinal fluid (CSF) histamine levels were found in human
      hypersomnia. To evaluate the functional significance of changes in CSF histamine
      levels, we measured the levels in rats across 24h, after the administration of
      wake-promoting compounds modafinil, amphetamine, and thioperamide, and after
      sleep deprivation and food deprivation. Thioperamide significantly increased CSF
      histamine levels with little effects on locomotor activation. Both modafinil and
      amphetamine markedly increased the locomotor activity, but had no effects on
      histamine. The levels are high during active period and are markedly elevated by
      sleep deprivation, but not by food deprivation. Our study suggests that CSF
      histamine levels in rats reflect the central histamine neurotransmission and
      vigilance state changes, providing deeper insight into the human data.

PMID- 18077093
TI  - Multivariate statistical approach to electron backscattered diffraction.
AB  - This paper assesses the potential of multivariate statistical analysis (MSA)
      applied to electron backscattered diffraction (EBSD) data. Instead of directly
      indexing EBSD patterns on an individual basis, this multivariate approach reduces
      a large (thousands) set of individual EBSD patterns into a core set of
      statistically derived component EBSD patterns which can be subsequently indexed.
      The following hypotheses are considered in this paper: (1) experimental EBSD
      patterns from a microstructure can be analytically treated as linear combinations
      of spatially simple components, (2) MSA has an angular resolution on par with
      standard EBSD, (3) MSA can discriminate between similar and dissimilar phases,
      and (4) the MSA approach can improve the effective spatial resolution of
      automated EBSD.

PMID- 18077094
TI  - Volcano structure in atomic resolution core-loss images.
AB  - A feature commonly present in simulations of atomic resolution electron energy
      loss spectroscopy images in the scanning transmission electron microscope is the
      volcano or donut structure. In the past this has been understood in terms of a
      geometrical perspective using a dipole approximation. It is shown that the dipole
      approximation for core-loss spectroscopy begins to break down as the probe
      forming aperture semi-angle increases, necessitating the inclusion of higher
      order terms for a quantitative understanding of volcano formation. Using such
      simulations we further investigate the mechanisms behind the formation of such
      structures in the single atom case and extend this to the case of crystals. The
      cubic SrTiO3 crystal is used as a test case to show the effects of nonlocality,
      probe channelling and absorption in producing the volcano structure in crystal
      images.

PMID- 18077095
TI  - Diagnostic real-time PCR assay for the quantitative detection of Theileria equi
      from equine blood samples.
AB  - We developed a TaqMan real-time polymerase chain reaction (PCR) assay for the
      quantitative detection of Theileria equi from the in vitro-cultured parasite and
      field blood samples collected from horses living in Ghana and Brazil. The
      detection limit for the assay was determined to be 1.5 parasites/microl per
      sample, and the quantitative capacity was demonstrated using the in vitro
      cultured parasite. For field applications, the real-time PCR assay was compared
      to a previously established nested PCR assay used as the gold standard for the
      real-time PCR assay. Of 65 field blood samples, 46 samples were T. equi-positive
      in the nested PCR assay, while the real-time PCR assay also detected the parasite
      in all 46 of the nested PCR-positive samples but did not detect T. equi in the
      remaining 19 negative blood samples. This quantitative real-time PCR assay
      provides a valuable tool for fast laboratory diagnostic assessment of T. equi
      infection in horses.

PMID- 18077096
TI  - Parascaris equorum in foals and in their environment on a Swedish stud farm, with
      notes on treatment failure of ivermectin.
AB  - Environmental contamination and the egg excretion pattern of the ascarid
      Parascaris equorum (Nematoda) was investigated in relation to anthelmintic
      treatment on a Swedish stud farm. Faecal samples from 15 foals, dewormed every
      8th-week with a paste formulation of ivermectin at the standard dose rate of 0.2
      mg/kg bodyweight, were collected at five sampling occasions between August and
      November 2006. In addition, soil samples were obtained from four paddocks used by
      these foals in November 2006. The number of eggs per gram (epg) was counted in
      both faeces and soil. Egg excretion started when the foals were 3-4 months, and
      reached the highest levels when they were approximately 5-month-old, and was then
      followed by a decline. Egg excretion seemed to be unaffected by ivermectin
      despite these foals were dewormed at regular intervals. In four out of five foals
      examined 10 days after treatment, epg actually increased. In contrast, when
      either fenbendazol or pyrantel embonate were used instead of ivermectin,
      treatments were effective. The number of eggs in soil was significantly higher in
      the permanent paddock compared to in the temporarily used soil paddock and in the
      summer paddocks.

PMID- 18077097
TI  - The Yin and Yang of lactosylceramide metabolism: implications in cell function.
AB  - Although lactosylceramide (LacCer) plays a pivotal role in the biosynthesis of
      nearly all the major glycosphingolipids, its function in regulating cellular
      function has begun to emerge only recently. Our current opinion is that several
      physiologically critical molecules such as modified/oxidized LDL, growth factors,
      pro-inflammatory cytokines and fluid shear stress converge upon and activate
      lactosylceramide synthase to generate LacCer. In turn, LacCer activates an
      "oxygen-sensitive" signaling pathway involving superoxides, nitric oxide, p21 Ras
      GTP loading, kinase cascade, PI3kinase/Akt activation, nuclear factor up
      regulation ultimately contributing to phenotypic changes such as cell
      proliferation, adhesion, migration and angiogenesis. Since dys-regulation of such
      phenotypic changes constitute a hallmark in several diseases of the
      cardiovascular system, proliferative disorders such as cancer, polycystic kidney
      disease and inflammatory diseases, LacCer synthase and LacCer provide novel
      targets for the development of therapeutics aimed at these health conditions.

PMID- 18077098
TI  - Biochemotherapy for the treatment of metastatic malignant melanoma: a systematic
      review.
AB  - BACKGROUND: The incidence of malignant melanoma has increased in recent years.
      Current therapies for metastatic melanoma include chemotherapy and a variety of
      immunotherapeutic choices. With no established standard treatment option, the
      evaluation of biochemotherapy is warranted. METHODS: A systematic review of the
      literature was conducted to locate randomized controlled trials, meta-analyses,
      systematic reviews, and evidence-based practice guidelines published up to April
      2007. RESULTS: Nine eligible randomized controlled trials were identified,
      including six comparing chemotherapy alone to biochemotherapy (chemotherapy
      combined with interleukin-2 and interferon). Response rates were significantly
      higher with biochemotherapy in only two trials, although when data were pooled,
      biochemotherapy was superior to chemotherapy on response (relative risk, 1.52;
      95% confidence interval, 1.24-1.87; p<0.0001) but did not delay time to
      progression (Hazard ratio, 0.80; 95% confidence interval, 0.63-1.01; p=0.06).
      Biochemotherapy was not associated with a statistically significant survival
      benefit in any of the individual trials or in a pooled analysis (Hazard ratio,
      0.95; 95% confidence interval, 0.78-1.17; p=0.64). Biochemotherapy is a toxic
      therapy, and patients are likely to experience serious hematologic,
      gastrointestinal, cutaneous, and constitutional toxicities, although when
      conducted in the correct setting, grade 3 and 4 effects appear to be manageable,
      and treatment-related death can be minimized. CONCLUSION: The results of
      available studies are inconsistent with regard to benefit (response, time-to
      progression, and survival) and show consistently high toxicity rates. Therefore,
      biochemotherapy is not recommended for the treatment of metastatic malignant
      melanoma in adults.

PMID- 18077100
TI  - EEG correlates of imagery-induced cigarette craving in male and female smokers.
AB  - Functional neuroimaging studies of cue-elicited craving in smokers have
      identified a distributed system of brain activation which includes the frontal
      cortex. As electroencephalographic (EEG) activity recorded from frontal brain
      regions indexes emotive functions, which are believed to play a key role in
      craving processes, this study examined frontal EEG in 20 cigarette smokers (10
      male) exposed to imagery scripts containing positive, negative, or neutral
      affective content with and without descriptions of smoking urges. Urge scripts
      increased subjective cravings related to both the rewarding and withdrawal-relief
      properties of smoking, the latter tending to be greater in female smokers, as
      were self-reports of frustration. The emotional content of scripts did not
      moderate urges or EEG but urge scripts were found to: a) decrease activity of
      delta in male smokers and to increase activity of beta, a pattern which has also
      been seen with acute smoking, and b) increase activity of theta, a response which
      has also been seen with smoking abstinence. This imagery-elicited neuroelectric
      profile, appearing to reflect opposing actions of reward and withdrawal, suggests
      that EEG may be a sensitive tool for probing the multidimensional nature of
      craving.

PMID- 18077101
TI  - NMDA receptor blockade: a novel avenue for tobacco intervention?

PMID- 18077099
TI  - Prenatal stress does not alter innate novelty-seeking behavioral traits, but
      differentially affects individual differences in neuroendocrine stress
      responsivity.
AB  - Exposure to stress during prenatal or early postnatal life can dramatically
      impact adult behavior and neuroendocrine function. We recently began to
      selectively breed Sprague-Dawley rats for high (high responder, HR) and low (low
      responder, LR) novelty-seeking behavior, a trait that predicts a variety of
      differences in emotional reactivity, including differences in neuroendocrine
      stress response, fear- and anxiety-like behavior, aggression, and propensity to
      self-administer drugs of abuse. We evaluated genetic-early environment
      interactions by exposing HR- and LR-bred animals to prenatal stress (PS) from
      pregnancy day 3-20, hypothesizing that PS exposure would differentially impact HR
      versus LR behavior and neuroendocrine reactivity. We evaluated novelty-induced
      locomotion, anxiety-like behavior, and corticosterone stress response in weanling
      (25-day-old) and adult HR-LR stressed and control males. Exposure to PS did not
      alter HR-LR differences in locomotion, but did impact anxiety-like behavior,
      specifically in LR animals. Surprisingly, LR animals exposed to PS exhibited less
      anxiety than LR controls. HR rats were not affected by PS, with both stress and
      control groups showing low levels of anxiety. PS differentially impacted
      neuroendocrine stress reactivity in young versus adult HR-LR animals, leading to
      an exaggerated corticosterone response in LR pups compared to LR controls, while
      HRs pups were unaffected. In contrast, exposure to PS produced an exaggerated
      stress response in HR adults, compared to HR controls, while LR animals were not
      significantly affected. These findings highlight how genetic predisposition may
      shape individual's response to early life stressors, and furthermore, show that a
      history of early life stress may differentially impact an organism at different
      points in life. Future work will explore neural mechanisms which underlie the
      different behavioral and neuroendocrine consequences of PS in HR versus LR
      animals.

PMID- 18077102
TI  - [Validity of local anesthesia for female stress urinary incontinence surgery with
      sub-urethral sling].
AB  - OBJECTIVE: To evaluate the feasibility and the comfort of the local anesthesia
      more or less associated with a light sedation for the sub-urethral vaginal tape
      in the urinary incontinence surgery. MATERIAL AND METHODS: In a series without
      selection, 138 patients, benefiting from the isolated sub-urethral vaginal tape
      surgery (51: Monarc; 18: TVT-O((R)) and 69: TVTSecur, are submitted, after
      premedication (alpazolam, hydroxyzine), to a pure local anesthesia (ropivacaine
      clonidine and adrenalin) for the TVTSecur and associated with a light sedation
      (midazolam-sufentan) for the TVT-O and Monarc. The anxiety, the peroperative pain
      and the satisfaction of patients have been evaluated by an analogical visual
      scale (EVA). RESULTS: No significant difference is put in obviousness for the
      preoperative anxiety in three groups, similarly for the peroperative pain
      classified in three group, EVA: 1-30, 40-60 and 70-100mm with, respectively, for
      Monarc 54.9, 35.3 and 7.8%, for TVT-O 77.8, 22.2 and 0% and for TVTSecur 47.8,
      43.5 and 8.7%. In the postoperative period, analgesics have been prescribed for
      92.2 and 94.4% of Monarc and TVT-O and for 7.2% of TVTSecur. More than 92% of
      patients recommend this type of anesthesia. DISCUSSION: Contrarily to the
      majority of authors that use a deep sedation, the weak dose that we have used
      allows a perfected vigilance. The interest of ropivacaine associated with
      clonidine was both to have a vasoconstrictor effect and a prolongation of the
      analgesic effect with a lesser toxic effect than lidocaine and bupivacaine.
      CONCLUSION: We militate for a return to a minimal invasive anesthesia as that
      described initially by promoters of the tension-free vaginal tape (TVT), that
      allows the sub-urethral vaginal tape surgery, under local anesthesia with light
      sedation, in ambulatory of comfortable manner for patients.

PMID- 18077103
TI  - [Spontaneous diaphragm rupture during delivery. Case report].
AB  - We report a case of spontaneous diaphragm rupture during delivery in a 42-year
      old woman. The patient presented at surgical emergency department with abdominal
      pains, vomiting and dyspnea, three days after full-term delivery. The X-ray of
      the chest and computed tomography showed symptoms of a left diaphragmatic
      rupture. Laparotomy confirmed the diaphragmatic rupture with herniation of
      portion of the stomach in the left pleural cavity. Spontaneous diaphragmatic
      rupture during delivery is uncommon and would result from a sudden sharp rise in
      the intra-abdominal pressure during the second stage of labor, exacerbated by
      application of external pressure to the uterine fundus or the upper abdomen.
      Diaphragmatic rupture during labor is a serious but rare complication that
      requires emergency surgery to prevent visceral perforation and cardiorespiratory
      failure. To prevent this complication, the delivery conditions should be
      improved.

PMID- 18077104
TI  - Transition to injection drug use among street youth--a qualitative analysis.
AB  - OBJECTIVES: To examine social contexts and processes influencing transition to
      drug injection among street youth. METHODS: 42 street youth participated in in
      depth interviews. A typology of experiences was built founded on youth's street
      life and drug use trajectories. The transition to drug injection was examined
      through these experiences. RESULTS: We identified five types of mutually
      exclusive experiences. The "downtowner's" experience is characterised by early
      street life and drug consumption trajectories, and a strong identification with
      the downtown milieu. These youth progress from one drug to another and, in a
      milieu where drug injection is omnipresent, this escalation culminates in
      transition to injection. The "tripper" street life and substance use trajectories
      begin later and are less intense. Most "tripper" youth are already chronic
      hallucinogens users when they arrive in downtown Montreal. Although they judge
      "junkies" severely, they show some ambivalence towards injection. The "on the go"
      experience is characterised by trajectories of drug use and street life that are
      intermingled, leading to a loss of control. These youth, who often have serious
      delinquent behaviours, come to downtown Montreal to party and consume drugs,
      mostly stimulants. Their drug use pattern and network make them at high risk of
      starting cocaine injection. The "hard-luck's" experience is characterised by a
      lack of identification with the downtown milieu. These youth who use drugs
      recreationally, end up in the streets accidentally, often because of
      unemployment. The "alcoholic' experience is related to alcohol misuse. These
      youth usually end up in the streets due to this dependence. Their street
      involvement is mostly an experience of solitude. The risk of transitioning to
      injection for both these types is low. CONCLUSIONS: Some combinations of street
      life and drug use trajectories seem to contribute to injection among street
      youth. Some important factors interact and increase the risk of street youth
      transitioning to injection: poor personal assets; early rupture with primary
      social institutions; social integration into subcultures where both street life
      and "drug trips" are fashionable, drug preferences and the local drug market.

PMID- 18077105
TI  - Choice of sevoflurane and its subjective and psychomotor effects in light and
      moderate drinkers.
AB  - BACKGROUND: Sevoflurane, an inhalant of the volatile anesthetic class, has
      neurobiological and behavioral effects in common with abused inhalants and
      ethanol. We sought to determine if choice for subanesthetic doses of sevoflurane,
      and its subjective and psychomotor effects, would differ as a function of alcohol
      drinking status in healthy volunteers. METHODS: The effects of four
      concentrations of sevoflurane (0, 0.2, 0.4, 0.8% sevoflurane in oxygen) were
      studied in 16 light drinkers and 16 moderate drinkers. During each of four
      sessions, subjects sampled a concentration of sevoflurane and 100% O(2) (placebo)
      for 10 min each. Subjective and psychomotor testing commenced 5 min into each
      sampling trial. Later, within the session, subjects chose nine times, once every
      5 min, among sevoflurane (e.g., "Agent A"), placebo (e.g., "Agent B," 100% O(2)),
      or neither (and were administered 100% O(2), identified as "drug-free air").
      RESULTS: Choice for sevoflurane at the 0.4% concentration was significantly
      higher in the moderate drinkers than in the light drinkers. A number of
      subjective effects reported during inhalation of sevoflurane were markedly lower
      in the moderate-drinking group than in the light-drinking group. However,
      psychomotor impairment induced by sevoflurane was similar in magnitude in both
      groups. CONCLUSIONS: Alcohol-drinking status affected sevoflurane choice. The
      results are consistent with several studies comparing light and heavier drinkers,
      using other drugs. Although both drinking groups were similarly impaired by
      sevoflurane, the moderate drinkers reported less of a subjective response than
      light drinkers, suggestive of cross-tolerance.

PMID- 18077106
TI  - A directional recombination cloning system for restriction- and ligation-free
      construction of GFP, DsRed, and lacZ transgenic Drosophila reporters.
AB  - The fruit fly Drosophila is a leading model system for the study of
      transcriptional control by cis-regulatory elements, or enhancers. Here we present
      a rapid, high-efficiency system for directionally cloning PCR-amplified, PCR
      mutated, or synthetic enhancer sequences into the Ganesh family of P element
      reporter constructs, which contain reporter genes encoding nuclear-localized
      eGFP, DsRed, or beta-galactosidase. This system, which is scalable for either
      small projects or high-throughput approaches, makes use of both TOPO and Gateway
      cloning technologies for directional, efficient cloning, without the need for
      restriction digestion or ligation reactions. It should be especially useful for
      those researchers who wish to test large numbers of putative enhancers, those who
      are undertaking detailed mutational analyses of enhancer sequences, or those who
      wish to avoid the difficulties sometimes encountered in traditional cloning
      strategies.

PMID- 18077107
TI  - Alternative polyadenylation signals in the 3' non-coding region of a voltage
      gated potassium channel gene are major determinants of mRNA isoform expression.
AB  - We investigated the role of the 3' non-coding region of a mouse voltage-gated
      potassium channel mRNA (mKv1.4 mRNA) in post-transcriptional regulation of gene
      expression. In contrast to an earlier report from studies carried out in Xenopus
      oocytes, we found that 3' non-coding region sequences of mKv1.4 mRNAs did not
      significantly affect expression of a heterologous reporter RNA in vitro or in
      mammalian cells/cell lines. Instead, our data revealed a possible role for
      alternative polyadenylation mediated by distinct determinants approximately 0.2
      kb and approximately 1.2 kb downstream of the Kv1.4 coding region. The use of the
      downstream polyadenylation signal correlated with the synthesis of a larger Kv1.4
      mRNA isoform that was more abundantly expressed than the smaller mRNA species,
      whose expression was regulated by the upstream polyadenylation signal. Our
      results suggest that the relative strengths of the polyadenylation signals are
      major determinants of overall Kv1.4 mRNA abundance in cells.

PMID- 18077108
TI  - siRNA-mediated knockdown of a splice variant of the PK-A catalytic subunit gene
      causes adult-onset paralysis in C. elegans.
AB  - In C. elegans, the PK-A catalytic subunit is encoded by kin-1, which has six 5'
      exons (N'1-N'6), any one of which may be alternatively spliced onto exon-2. Here
      we describe a novel siRNA-based strategy to knockdown the expression levels of
      the N'3 and N'4 splice variants. We show that this technique can effectively
      knockdown expression of the targeted isoforms without affecting expression of the
      other kin-1 splice variants. We suggest that this strategy could be widely used
      in C. elegans to investigate the function of genes with alternative first exons.
      Moreover, we report a novel role for the N'3 kin-1 variant. Whereas knockdown of
      the N'4 variant results in no obvious phenotype, loss of the N'3 variant leads to
      paralysis and an egg-laying defect in the adult, suggesting a deficit in the
      function of the neuromuscular junction. The function of the N'3 variant is
      discussed in relation to the known function of PK-A in regulation of the release
      of neurotransmitters from many presynaptic termini.

PMID- 18077109
TI  - Facilities for transcription and mobilization of an exon-less bacterial group II
      intron nested in transposon TnMERI1.
AB  - Transcription and mobilization facilities of a group II intron, B.me.I1, which
      was classified within a group IIB subclass and nested in a broad-spectrum mercury
      resistance transposon TnMERI1 found from the chromosome of Bacillus megaterium
      strain MB1 were investigated. Though B.me.I1 does not intervene in any
      recognizable exon gene, the splicing ability of B.me.I1 in Escherichia coli was
      confirmed by applying RT-PCR with RNA template transcribed by using a T7 RNA
      polymerase-promoter expression system. The homing activity of B.me.I1 was
      confirmed by using an intron-less allele fragment as a specific integration site
      which was cloned from Tn5084, a TnMERI1-family mercury resistance transposon. The
      transcription and splicing of B.me.I1 in the original host, the strain MB1, were
      also observed as its natural property. Primer-walking and 5' RACE analyses showed
      that the transcription start site and the putative promoter region of B.me.I1
      were located on the antisense strand of tnpR gene of TnMERI1. Therefore, it is
      cleared that TnMERI1 provides a specific integration site and facilities for
      transcription of B.me.I1. From these results, it is considered that these genetic
      facilities given by the transposon TnMERI1 confer splicing and homing capability
      on B.me.I1, even though the group II intron is not associated with any exon gene.

PMID- 18077110
TI  - Molecular epidemiological analyses of the teratogenic Aino virus based on the
      sequences of a small RNA segment.
AB  - The sequences of a small RNA segment of Aino virus isolates were analyzed to
      define the molecular epidemiology and genetic relationships to other species in
      the genus Orthobunyavirus in the family Bunyaviridae. The nucleotide and amino
      acid sequences of the segment were highly conserved among strains isolated from
      1964 to 2002 in Japan. These Japanese isolates were segregated into two distinct
      lineages, one containing the prototype strain JaNAr28 isolated in 1964 and the
      other containing strains isolated after 1986, by phylogenetic analysis based on
      the nucleocapsid gene sequences. Japanese strains isolated after 1986 were rather
      more closely related to Kaikalur virus isolated in India in 1971 than to strain
      JaNAr28. On the other hand, an Australian strain, B7974, was closely related to
      Peaton virus. The B7974 strain might have been generated by inter-serotype
      genetic reassortment between Aino and Peaton viruses in Australia during their
      evolution. However, recent Aino virus strains isolated in Japan appear to be
      genetically stable.

PMID- 18077111
TI  - Pathogenicity and transmission studies of H5N2 parrot avian influenza virus of
      Mexican lineage in different poultry species.
AB  - In 2004, a low pathogenic H5N2 influenza virus (A/parrot/CA/6032/04) was
      identified in a psittacine bird for the first time in the United States. Sequence
      and phylogenetic analysis of the hemagglutinin gene grouped the parrot isolate
      under the Mexican lineage H5N2 viruses (subgroup B) with highest similarity to
      recent chicken-origin isolates from Guatemala. Antigenic analysis further
      confirmed the close relatedness of the parrot isolate to Mexican lineage viruses,
      the highest cross-reactivity being demonstrated to Guatemala isolates. In vivo
      studies of the parrot isolate in chickens, ducks and turkeys showed that the
      virus, though did not cause any clinical signs, could replicate to high titers in
      these birds and efficiently transmit to contact control cage mates. The
      possibility that the parrot harboring the virus was introduced into the United
      States as a result of illegal trade across the border provides additional concern
      for the movement of foreign animal diseases from neighboring countries.
      Considering the potential threat of the virus to domestic poultry, efforts should
      be continued to prevent the entry and spread of influenza viruses by imposing
      effective surveillance and monitoring measures.

PMID- 18077112
TI  - Phenotypes and genotypes of campylobacter strains isolated after cleaning and
      disinfection in poultry slaughterhouses.
AB  - Campylobacter is responsible for human bacterial enteritis and poultry meat is
      recognised as a primary source of infection. In slaughterhouses, cleaning and
      disinfection procedures are performed daily, and it has been suggested that
      disinfectant molecules might select for antibiotic resistant strains if shared
      targets or combined resistance mechanisms were involved. The aim of the study was
      to investigate if cleaning and disinfection procedures in poultry slaughterhouses
      select for antibiotic resistance in Campylobacter jejuni and C. coli and to
      determine the genotypes of isolates collected after cleaning and disinfection.
      Nine sampling visits were made to four French slaughterhouses. Samples were
      collected from transport crates and equipment surfaces, before and after cleaning
      and disinfection. Minimal inhibitory concentrations of the recovered C. jejuni
      and C. coli isolates to six antibiotics and two disinfectants were measured. The
      C. jejuni isolates collected from equipment surfaces after cleaning and
      disinfection were subjected to PCR-RFLP typing. Twenty-five C. jejuni isolates
      and 1 C. coli were recovered from equipment surfaces after cleaning and
      disinfection during five visits to three different slaughterhouses. Those
      isolates did not show an increased resistance to the tested antibiotics compared
      to isolates collected before cleaning and disinfection. Only one or two genotypes
      were recovered after cleaning and disinfection during single visits to each
      slaughterhouse. This observation suggests that such genotypes may be particularly
      adapted to survive cleaning and disinfection stress. Understanding the survival
      mechanisms of Campylobacter should facilitate the implementation of better
      targeted strategies and reduce the public health burden associated with
      Campylobacter infection.

PMID- 18077113
TI  - Human pharmaceuticals in surface waters. Implementation of a prioritization
      methodology and application to the French situation.
AB  - Human pharmaceuticals are widely used and can reach surface waters, where they
      have the potential to exert biological effects on aquatic non-target organisms.
      Due to the high number of pharmaceutical drugs used in human medicine throughout
      the world, it is necessary to select the pharmaceuticals to search for, prior to
      implementing any environmental measurements and any extensive environmental risk
      assessment (ERA). This paper describes a methodology developed in order to define
      this selection. The prioritization scheme consists in three tiers. First, a
      preliminary classification based on the assessment of exposure is implemented.
      This exposure assessment is determined by calculating predicted environmental
      concentrations (PECs) for each pharmaceutical according to the European Medicine
      Evaluation Agency's (EMEA's) environmental risk assessment guidelines [EMEA,
      2006. European Medicine Agency Guideline on the Environmental Risk Assessment of
      Medicinal Products for Human Use. EMEA/CHMP/SWP/4447/00.]. In the second step,
      the preliminary classification is reviewed on a case-by-case hypothesis basis
      using all the biological data available: ecotoxicological, pharmacological
      (mechanism of action (MoA), enzyme modulation, adverse effects) and
      physicochemical data (log K(ow)). Finally, an additional step is used to select
      priority compounds among molecules showing the same chemical structure and the
      same mechanism of action. We applied this methodology to the French situation and
      prioritized 120 parent molecules and 30 metabolites. The final prioritization
      list gathers 40 parent compounds and 14 metabolites. Among the 40 parent
      molecules, 21 have already been found in the aquatic environment, indicating a
      good agreement between the theoretical approach and the environmental
      measurements. Parameters used to construct the effect criteria are discussed for
      their relevance.

PMID- 18077114
TI  - Gene expression profiling in rat cerebellum following in utero and lactational
      exposure to mixtures of methylmercury, polychlorinated biphenyls and
      organochlorine pesticides.
AB  - Although human populations are continuously exposed to complex mixtures of
      contaminants, the effects of such exposure on the developing brain transcriptome
      are poorly characterized. Rats were exposed perinatally to the northern
      contaminant mixture (NCM) which was designed to reflect the blood contaminant
      profile of Canadian arctic populations, to components of the NCM administered
      separately (methylmercury (MeHg), polychlorinated biphenyls (PCBs) and
      organochlorine pesticides (OCs)) or to the goitrogen propylthiouracyl. Post-natal
      day (PND) 14 cerebellum global gene expression resulting from such exposures was
      investigated using high-density cDNA microarrays. Fifty known genes were
      identified as differentially expressed between the control group and at least one
      other treatment group. The microarray data were validated by quantitative PCR
      (qPCR) on a subset of 10 genes. The differentially expressed genes are involved
      in a variety of processes, including nerve cell differentiation, migration,
      myelination and synaptic transmission. The comparison of cerebellum gene
      expression profiles resulting from exposure to the NCM and its individual
      components in male and female pups revealed that (i) gender is a crucial
      biological variable influencing genomic response to environmental contaminants
      and (ii) contaminant co-exposure significantly masks the effects of individual
      mixture components on cerebellum gene expression.

PMID- 18077115
TI  - The role of space charge formation in the generation of thermally stimulated
      current (TSC) spectroscopy data for a model amorphous drug system.
AB  - Thermally stimulated current (TSC) spectroscopy is attracting increasing
      attention as a means of materials characterization, particularly in terms of
      measuring slow relaxation processes in solid samples. However, wider use of the
      technique within the pharmaceutical field has been inhibited by difficulties
      associated with the interpretation of TSC data, particularly in terms of
      deconvoluting dipolar relaxation processes from charge distribution phenomena.
      Here, we present evidence that space charge and electrode contact effects may
      play a significant role in the generation of peaks that have thus far proved
      difficult to interpret. We also introduce the use of a stabilization temperature
      in order to control the space charge magnitude. We have studied amorphous
      indometacin as a model drug compound and have varied the measurement parameters
      (stabilization and polarization temperatures), interpreting the changes in
      spectral composition in terms of charge redistribution processes. More
      specifically, we suggested that charge drift and diffusion processes, charge
      injection from the electrodes and high activation energy charge redistribution
      processes may all contribute to the appearance of shoulders and 'spurious' peaks.
      We present recommendations for eliminating or reducing these effects that may
      allow more confident interpretation of TSC data.

PMID- 18077116
TI  - Towards a unifying basis of auditory thresholds: distributions of the first-spike
      latencies of auditory-nerve fibers.
AB  - Detecting sounds in quiet is the simplest task performed by the auditory system,
      but the neural mechanisms underlying perceptual detection thresholds for sounds
      in quiet are still not understood. Heil and Neubauer [Heil, P., Neubauer, H.,
      2003. A unifying basis of auditory thresholds based on temporal summation. Proc.
      Natl. Acad. Sci. USA 100, 6151-6156] have provided evidence for a simple
      probabilistic model according to which the stimulus, at any point in time, has a
      certain probability of exceeding threshold and being detected. Consequently, as
      stimulus duration increases, the cumulative probability of detection events
      increases, performance improves, and threshold amplitude decreases. The origin of
      these processes was traced to the first synapse in the auditory system, between
      the inner hair cell and the afferent auditory-nerve fiber (ANF). Here we provide
      further support for this probabilistic "continuous-look" model. It is derived
      from analyses of the distributions of the latencies of the first spikes of cat
      ANFs with very low spontaneous discharge rates to tones of different amplitudes.
      The first spikes in these fibers can be considered detection events. We show
      that, as predicted, the distributions can be explained by the joint probability
      of the occurrence of three independent sub-events, where the probability of each
      of those occurring is proportional to the low-pass filtered stimulus amplitude.
      The "temporal integration" functions of individual ANFs, derived from their first
      spike latencies, are remarkably similar in shape to "temporal integration"
      functions, which relate threshold sound pressure level at the perceptual level to
      stimulus duration. This further supports a close link between the mechanisms
      determining the timing of the first (and other) evoked spikes at the level of the
      auditory nerve and detection thresholds at the perceptual level. The possible
      origin and some functional consequences of the expansive power-law non-linearity
      are discussed.

PMID- 18077117
TI  - Effects of exposing C57BL/6J mice to high- and low-frequency augmented acoustic
      environments: auditory brainstem response thresholds, cytocochleograms, anterior
      cochlear nucleus morphology and the role of gonadal hormones.
AB  - Gonadectomized and intact adult C57BL/6J (B6) mice of both sexes were exposed for
      12h nightly to an augmented acoustic environment (AAE): repetitive bursts of a
      70dB SPL noise band. The high-frequency AAE (HAAE) was a half-octave band
      centered at 20kHz; the low-frequency AAE (LAAE) was a 2-8kHz band. The effects of
      sex, gonadectomy, and AAE treatment on genetic progressive hearing loss (a trait
      of B6 mice) were evaluated by obtaining auditory brainstem response (ABR)
      thresholds at ages 3-, 6-, and 9-months. At 9-months of age, hair cell counts
      (cytocochleograms) were obtained, and morphometric measures of the anteroventral
      cochlear nucleus (AVCN) were obtained. LAAE treatment caused elevation in ABR
      thresholds (8-24kHz), with the highest thresholds occurring in intact females.
      LAAE treatment caused some loss of outer hair cells in the basal half of the
      cochlea (in addition to losses normally occurring in B6 mice), with intact
      females losing more cells than intact males. The loss of AVCN neurons and
      shrinkage of tissue volume that typically occur in 9-month-old B6 mice was
      lessened by LAAE treatment in intact (but not gonadectomized) male mice, whereas
      the degenerative changes were exacerbated in intact (but not gonadectomized)
      females. These LAAE effects were prominent in, but not restricted to, the
      tonotopic low-frequency (ventral) AVCN. HAAE treatment resulted in some loss of
      neurons in the high-frequency (dorsal) AVCN. In general, LAAE treatment plus male
      gonadal hormones (intact males) had an ameliorative effect whereas HAAE or LAAE
      treatment plus ovarian hormones (intact females) had a negative effect on age
      related changes in the B6 auditory system.

PMID- 18077118
TI  - Anti-allergic activity of compounds from Kaempferia parviflora.
AB  - Kaempferia parviflora is one of the plants in the Zingiberaceae family, locally
      known in Thai as kra-chai-dam. In Thai traditional medicine, the decoction of
      Kaempferia parviflora powder with alcohol has been reported to cure allergy,
      asthma, impotence, gout, diarrhea, dysentery, peptic ulcer and diabetes.
      Therefore, the present study aimed to investigate anti-allergic substances from
      this plant. Bioassay-guided fractionation led to the isolation of seven
      methoxyflavone derivatives (1-7) from Kaempferia parviflora extract and they were
      identified on the basis of spectroscopic methods. Among the compounds tested, 5
      hydroxy-3,7,3',4'-tetramethoxyflavone (5) possessed the highest anti-allergic
      activity against antigen-induced beta-hexosaminidase release as a marker of
      degranulation in RBL-2H3 cells with an IC(50) value of 8.0 microM, followed by 5
      hydroxy-7-methoxyflavone (2, IC(50)=20.6 microM) and 5-hydroxy-7,4'
      dimethoxyflavone (4, IC(50)=26.0 microM), whereas others showed moderate
      activities (IC(50)=37.5-66.5 microM). Structure-activity trends of 7
      methoxyflavone derivatives on anti-allergic activity can be summarized as
      follows: (1) substitution with vicinal methoxyl groups at positions 3' and 4'
      conferred higher activity than only one methoxylation, (2) methoxylation at
      position 3 reduced activity and (3) methoxylation at position 5 showed higher
      activity than hydroxylation. Compounds 2, 4 and 5 were also determined for their
      mechanisms on ionomycin-induced beta-hexosaminidase release. The results
      indicated that the mechanism on inhibition of cell degranulation of compounds 2
      and 5 mainly involve the inhibition of Ca(2+) influx to the cells, whereas that
      of 4 may be partly due to this inhibition. In regards to the active constituents
      for anti-allergic activity of Kaempferia parviflora, 5-hydroxy-3,7,3',4'
      tetramethoxyflavone (5), 5-hydroxy-7-methoxyflavone (2) and 5-hydroxy-7,4'
      dimethoxyflavone (4) are responsible for anti-allergic effect of this plant. The
      findings support the traditional use of Kaempferia parviflora rhizomes for
      treatment of allergy and allergy-related diseases.

PMID- 18077119
TI  - Cardiac MRI of ischemic heart disease at 3 T: potential and challenges.
AB  - Cardiac MRI has become a routinely used imaging modality in the diagnosis of
      cardiovascular disease and is considered the clinically accepted gold standard
      modality for the assessment of cardiac function and myocardial viability. In
      recent years, commercially available clinical scanners with a higher magnetic
      field strength (3.0 T) and dedicated multi-element coils have become available.
      The superior signal-to-noise ratio (SNR) of these systems has lead to their rapid
      acceptance in cranial and musculoskeletal MRI while the adoption of 3.0 T for
      cardiovascular imaging has been somewhat slower. This review article describes
      the benefits and pitfalls of magnetic resonance imaging of ischemic heart disease
      at higher field strengths. The fundamental changes in parameters such as SNR,
      transversal and longitudinal relaxation times, susceptibility artifacts, RF (B1)
      inhomogeneity, and specific absorption rate are discussed. We also review
      approaches to avoid compromised image quality such as banding artifacts and
      inconsistent or suboptimal flip angles. Imaging sequences for the assessment of
      cardiac function with CINE balanced SSFP imaging and MR tagging, myocardial
      perfusion, and delayed enhancement and their adjustments for higher field imaging
      are explained in detail along with several clinical examples. We also explore the
      use of parallel imaging at 3.0 T to improve cardiac imaging by trading the SNR
      gain for higher field strengths for acquisition speed with increased coverage or
      improved spatial and temporal resolution. This approach is particularly useful
      for dynamic applications that are usually limited to the duration of a single
      breath-hold.

PMID- 18077120
TI  - Determination of ephedrine alkaloids in Ephedra natural products using HPLC on a
      pentafluorophenylpropyl stationary phase.
AB  - In this study a pentafluorophenylpropyl (PFPP) stationary phase was applied to
      the fast and reliable qualitative and quantitative analysis of ephedrine
      alkaloids in Ephedra plant material and derivatives. A Discovery HS F5 column
      (150mmx4.6mm i.d., 5microm) was used, with an isocratic mobile phase composed of
      ammonium acetate (7mM) in acetonitrile-water (90:10, v/v), at a flow rate of
      1.0ml/min. The column temperature was set at 45 degrees C. UV detection was set
      at 215 and 225nm. The total analysis time was 16min. The validation parameters,
      such as linearity, sensitivity, accuracy, precision and specificity, were found
      to be highly satisfactory. Sonication and microwave extractions were compared in
      order to optimize the yield of the target analytes. Under the optimized
      extraction conditions (based on two cycles of sonication with methanol at 40
      degrees C for 15min), different matrices containing Ephedra were successfully
      analyzed for their alkaloid content. The method was applied to the analysis of
      standard reference materials (SRMs) containing Ephedra. Furthermore, the
      developed technique allowed the simultaneous determination of ephedrine alkaloids
      and synephrine, the main phenethylamine alkaloid of Citrus aurantium, that has
      replaced Ephedra in dietary supplements used in the treatment of obesity. The
      results indicated that this procedure is suitable for the phytochemical analysis
      of Ephedra plant material and extracts, and can be applied to demonstrate the
      label claims for product content, including the absence of ephedrine alkaloids in
      Ephedra-free products.

PMID- 18077121
TI  - Evolution of macrolide resistance in Streptococcus pneumoniae clinical isolates
      in the prevaccine era.
AB  - Six hundred twelve invasive and noninvasive Streptococcus pneumoniae isolates
      were examined. Serogrouping was performed by the latex agglutination test and
      serotyping by the quellung reaction. Susceptibilities to macrolides were
      determined by Etest. The presence of mef(A), mef(E), and erm(B) genes were
      detected by polymerase chain reaction. Outpatient macrolide and lincosamide
      consumption was expressed in defined daily doses per 1000 inhabitants daily
      (DID). A significant increase in macrolide resistance rate was noted from 7.4%
      (14/190) in the period 1985 to 1996 to 53.7% (144/268) in 2001 to 2004 (P =
      0.003). An increase in macrolide and lincosamide consumption was also observed
      from 4.31 +/- 0.72 in 1990 to 1996 to 6.97 +/- 1.02 DID in 2001 to 2004 (P =
      0.002). Macrolide resistance was mediated by mef(E) gene in 44.5% of isolates,
      mef(A) in 25.6%, erm(B) in 19.8%, both erm(B) and mef(E) genes in 4.8%, and none
      of the examined genes in 5.3%. In the setting of increasing macrolide use, there
      has been a parallel increase in macrolide resistance among pneumococci in our
      region. The predominant resistance determinants were the mef(A) and mef(E) genes.

PMID- 18077122
TI  - Myiasis of the scalp due to Dermatobia hominis in a traveler returning from
      Brazil.
AB  - This article describes a case of myiasis by Dermatobia hominis diagnosed in a
      young Italian man returning from a vacation through Brazil. Considering the
      increasing number of travels to tropical and subtropical areas, clinicians in
      nonendemic areas must think about the possibility of imported unusual
      infestations during their daily practice.

PMID- 18077123
TI  - Peer-counseling in schizophrenia: patients consult patients.
AB  - OBJECTIVE: To evaluate whether peer-counseling, common in non-psychiatric medical
      fields, is feasible and useful for inpatients with schizophrenia. METHODS: The
      participants of a one-to-one peer-counseling were given the opportunity to
      present all questions related to their illness to a peer-counselor, who had
      himself been living with a schizoaffective disorder for over 20 years. The peer
      counseling was evaluated by the participants (STEPP-questionnaire), by the
      counselor (structured protocol) and by a physician (supervision). Descriptive
      methods were used for statistical analyses. RESULTS: Eighty-eight patients (mean
      age 37 years, 35% female, hospitalized for 5 weeks) took part. The main topics
      addressed were 'symptoms of schizophrenia'; main suggestions were 'taking
      medication for symptom control and relapse prevention', 'having patience' and
      providing 'emotional support'. The mean ratings in the STEPP-subscales were:
      relationship-perspective 18.6 out of 21, problem-solving 19.8 out of 28,
      clarification-perspective 24.9 out of 35. Ninety-six percent of the participants
      would recommend this peer-counseling to others. CONCLUSIONS: The results of this
      pilot-study show that peer-counseling is feasible in schizophrenia. The peer
      counselor was able to answer the questions adequately; patients felt well
      understood and obtained support and encouragement. PRACTICE IMPLICATIONS: The
      data suggest that peer-counseling is a potentially useful, additional tool for
      inpatients with schizophrenia as it appears to meet as yet unattended needs.

PMID- 18077124
TI  - Outcomes of neonates conceived on methadone maintenance therapy.
AB  - To assess potential risks related to the duration or total amount of fetal
      methadone exposure during gestation, we compared babies of women who conceived
      and maintained on methadone throughout pregnancy with babies of women who began
      methadone treatment during the second or third trimester. Babies conceived on
      methadone were exposed to the medication for a mean of 37.4 weeks at a mean dose
      of 110 mg/day, whereas comparison babies were exposed for a mean of 13.1 weeks at
      a mean dose of 93 mg/day. There were no significant between-group differences in
      the frequency of treatment of neonatal abstinence, days hospitalized, birth
      weight, or gestational age. Babies conceived on methadone were significantly less
      likely to test positive for illicit drugs at delivery as compared with babies
      conceived off methadone (positive toxicology, 9.1% vs. 34.3%, respectively).
      Methadone exposure during the entire gestational period was associated with
      better drug-treatment outcomes but was not associated with more severe neonatal
      abstinence.

PMID- 18077126
TI  - [Which anaesthesia techniques for difficult intubation? Particular situations:
      question 3. Societe Francaise d'Anesthesie et de Reanimation].

PMID- 18077125
TI  - [Difficult airway-management devices. Establishment and maintenance: question 4.
      Societe Francaise d'Anesthesie et de Reanimation].

PMID- 18077127
TI  - [Paraplegia after inadvertent epidural administration of potassium chloride].

PMID- 18077128
TI  - [Intrathecal use of amikacin and colistin].

PMID- 18077129
TI  - 6-O-Angeloylenolin induces apoptosis through a mitochondrial/caspase and NF
      kappaB pathway in human leukemia HL60 cells.
AB  - 6-O-Angeloylenolin, a sesquiterpene lactone from Centipeda minima, has been known
      to have anti-tumor activity against human colorectum, liver, stomach, lung, and
      skin tumor cells. However, its molecular mechanism is still obscure and
      insufficient in in vivo tests. In this study, we demonstrated that 6-O
      angeloylenolin could induce apoptosis in human leukemia HL60 cells through
      stimulating the generation of reactive oxygen species, decreasing mitochondrial
      trans-membrane potential (DeltaPsim) and activating caspase-3/7. We also found
      that 6-O-angeloylenolin could inhibit nuclear translocation of NF-kappaB and
      modulate the expression of Bcl-2 gene family. These results indicated that 6-O
      angeloylenolin induces apoptosis by inhibition of NF-kappaB activation,
      modulation of Bcl-2 gene family expression and destruction of mitochondrial
      function. Furthermore, we confirmed that 6-O-angeloylenolin could obviously
      inhibit the solid cancer growth in Lewis lung cancer xenograft models.

PMID- 18077130
TI  - [Nonsurgical treatment of chronic radiation-induced hemorrhagic proctitis].
AB  - The incidence of radiation-induced chronic hemorrhagic proctitis is less than 10
      to 20%. The onset of this proctitis is delayed relative to the radiation therapy
      and generally develops from 6 to 24 months later. There are numerous predisposing
      factors, the most important of which is the radiation therapy dose: risk
      increases exponentially above 40-45 Gy. Its pathophysiology involves progressive
      obliterating endarteritis and transmural interstitial fibrosis, which induce
      chronic ischemia that is irreversible and progressive during the years after
      radiation therapy. Its diagnosis depends most often on the combination of
      clinical history and typical endoscopic appearance (congestive mucosa and/or
      telangiectases). Topical administrative of sucralfate or corticosteroids as well
      as argon plasma coagulation, with formalin treatment if necessary, provides
      relief for most patients.

PMID- 18077131
TI  - Antigenotoxicity and antimutagenicity of lycopene in HepG2 cell line evaluated by
      the comet assay and micronucleus test.
AB  - Epidemiological studies have provided evidence that high consumption of tomatoes
      effectively reduces the risk of reactive oxygen species (ROS)-mediated diseases
      such as cancer. Tomatoes are rich sources of lycopene, a potent singlet oxygen
      quenching carotenoid. In addition to its antioxidant properties, lycopene shows
      an array of biological effects including antimutagenic and anticarcinogenic
      activities. In the present study, the chemopreventive action of lycopene was
      examined on DNA damage and clastogenic or aneugenic effects of H2O2 and n
      nitrosodiethylamine (DEN) in the metabolically competent human hepatoma cell line
      (HepG2 cells). Lycopene at concentrations of 10, 25, and 50 microM, was tested
      under three protocols: before, simultaneously, and after treatment with the
      mutagen, using the comet and micronucleus assays. Lycopene significantly reduced
      the genotoxicity and mutagenicity of H2O2 in all of the conditions tested. For
      DEN, significant reductions of primary DNA damage (comet assay) were detected
      when the carotenoid (all of the doses) was added in the cell culture medium
      before or simultaneously with the mutagen. In the micronucleus test, the
      protective effect of lycopene was observed only when added prior to DEN
      treatment. In conclusion, our results suggest that lycopene is a suitable agent
      for preventing chemically-induced DNA and chromosome damage.

PMID- 18077132
TI  - Fetal exposure to isotretinoin-an international problem.
AB  - BACKGROUND: Isotretinoin is a known teratogen. Pregnancy prevention programs
      aimed at minimizing isotretinoin exposure in pregnancy have been implemented in
      North America with limited success. OBJECTIVE: To compare the management of fetal
      risk of isotretinoin in three countries, including information given to women,
      implementation of contraceptive methods, and pregnancy outcomes. METHODS:
      Pregnant women exposed to isotretinoin who called teratogen information services
      (TIS) in Israel, Italy and Canada between July 1998 and October 2006 were
      interviewed at the time of initial consultation and after the expected day of
      delivery. RESULTS: Fifty-three pregnant women exposed to isotretinoin contacted
      the TIS. Only 41% reported using a birth control method. Just one patient
      reported using two different forms. Forty-five percent of exposed pregnancies
      were terminated before delivery and 22% delivered healthy babies. Two babies were
      born with malformations. CONCLUSIONS: Since isotretinoin-exposed pregnancies
      still occur, there is a need for more effective strategies, which should take
      into account the cultural differences.

PMID- 18077133
TI  - Breast tumor kinase BRK requires kinesin-2 subunit KAP3A in modulation of cell
      migration.
AB  - BReast tumor Kinase (BRK) also known as protein kinase 6 (PTK6) is a nonreceptor
      tyrosine kinase overexpressed in the majority of human breast tumors. Although
      some studies have implicated BRK in signalling, cell proliferation and migration,
      the precise intracellular role of BRK has not been fully elucidated. The RNA
      binding protein Sam68, and adaptor proteins paxillin and STAT3 are the only BRK
      substrates that link BRK to signal transduction. To identify new BRK substrates,
      we screened high-density protein filter arrays by large-scale in vitro kinase
      assays using active recombinant BRK. We identified at least 4 BRK targets
      comprising the alpha-subunit of stimulatory guanine nucleotide binding protein
      (GNAS), FL139441, beta-tubulin and kinesin associated protein 3A (KAP3A) and
      validated them as BRK substrates using a secondary assay. Further
      characterization revealed that KAP3A is an in vivo substrate of BRK and
      associates with BRK in breast cancer cells. We show that BRK specifically
      phosphorylated tyrosine residues at the C-terminus of KAP3A and induces
      delocalization of KAP3A from punctate nuclear localization to a diffuse nucleo
      cytoplasmic pattern. Functionally, we demonstrate that KAP3A knockdown results in
      suppression of BRK-induced migration of breast cancer cells and show that the C
      terminal deletion mutant of KAP3A acts as a dominant negative in BRK-induced cell
      migration. Our findings therefore reveal new substrates of BRK and define KAP3A
      as a physiological substrate of BRK during cell migration.

PMID- 18077134
TI  - Effect of zinc supplementation on protein metabolism in late-middle-aged men: The
      Zenith study.
AB  - OBJECTIVE: Zinc (Zn) is an essential trace element that is a potent enhancer of
      protein metabolism due to its numerous roles in metabolic processes. Protein
      turnover decreases with age. We determined whether a Zn supplementation, which
      increases serum Zn concentration and Zn exchangeable pool mass, modifies whole
      body protein turnover and albumin and fibrinogen synthesis rates in late-middle
      aged men. METHODS: Three groups of 16 healthy subjects 55-70 y of age
      participated in a randomized, doubled-blinded, placebo-controlled intervention.
      Each group received 0, 15, or 30 mg/d of supplemental Zn for 6 mo. At the end of
      the supplementation period, each subject received an intravenous infusion of L-[1
      13C] leucine to quantify whole-body leucine fluxes and synthesis rates of albumin
      and fibrinogen. RESULTS: In the placebo group, mean +/- SEM whole-body leucine
      fluxes to protein synthesis, to oxidation, and from protein degradation were 1.46
      +/- 0.05, 0.40 +/- 0.01, and 1.73 +/- 0.06 micromol.kg(-1).min(-1), respectively.
      Zn supplementation did not significantly change whole-body leucine fluxes. In the
      placebo group, plasma concentration and fractional rate of protein synthesis were
      45 +/- 1 g/L and 8.2 +/- 0.6%/d for albumin and 3.6 +/- 0.2 g/L and 16.7 +/-
      1.3%/d for fibrinogen, respectively. Zn supplementation did not significantly
      change these parameters or the absolute rates of synthesis of these proteins.
      CONCLUSION: Increasing Zn supply does not modify whole-body protein metabolism
      and synthesis rates of albumin and fibrinogen in late-middle-aged men.

PMID- 18077135
TI  - Prognosis after late relapse following epilepsy surgery.
AB  - OBJECTIVES: To assess prognosis after late relapse in patients who are seizure
      free for the first 5 years after epilepsy surgery. METHODS: Patients who were
      seizure free for the first 5 years after resective epilepsy surgery were
      included. Date of first seizure recurrence, current seizure status, medication,
      age, and type of surgery were prospectively registered. Non-parametric statistics
      were used. RESULTS: One hundred and fifty-nine patients were studied. Thirty-two
      had at least one recurrent seizure. Time to event analysis showed an annual
      relapse rate of 4% between years 5 and 10 after surgery. At study termination,
      143 of 159 patients (89.9%) were in terminal remission. For 30 patients with late
      relapse and at least 1-year follow-up thereafter, 53% were in terminal remission
      and 30% had experienced only rare or nocturnal seizures. Medication use was not
      associated either with likelihood of relapse or entering remission after relapse.
      CONCLUSIONS: Patients who are seizure free for the first 5 years after epilepsy
      surgery remain at risk for seizure recurrence. These relapses are often isolated
      events, and the long-term prognosis after relapse is often good. Relapse rates
      were similar in patients on and off AEDs, but the relation between AED taper and
      relapse is uncertain since patient groups may not be similar.

PMID- 18077136
TI  - A randomized double-blind comparison of ziprasidone vs. clozapine for cognition
      in patients with schizophrenia selected for resistance or intolerance to previous
      treatment.
AB  - BACKGROUND: Recent data have suggested few differences in the cognitive effects
      of antipsychotic medications. However, assessment of such effects can be complex,
      due to a number of factors. Clozapine has previously shown greater clinical and
      lesser cognitive benefits than other atypicals. This study compared the cognitive
      benefits of clozapine and ziprasidone in schizophrenia patients (n=130) with a
      history of either failure to respond to or intolerance of previous adequate
      antipsychotic treatments. METHODS: Patients were randomized (double-blind) to
      either clozapine or ziprasidone in a single country (Italy), multi-site trial.
      The cognitive assessments examined episodic memory (RAVLT), executive functioning
      (Stroop test), and processing speed (Trail-making test (TMT) Parts A and B).
      RESULTS: Analyses found statistically significant within-group improvements for
      ziprasidone in learning and delayed recall on the RAVLT and on TMT Parts A and B.
      Clozapine-treated patients improved on the RAVLT, but not on the TMT. A composite
      cognitive score improved from baseline in both groups, but the improvements were
      significantly larger in the ziprasidone group (p=.029). IMPLICATIONS: These
      results indicated that cognitive functioning improved following treatment with
      ziprasidone in patients with a history of either treatment resistance or
      intolerance, and that the effects are comparable or greater than those observed
      with clozapine. One interpretation of these findings is that clozapine treatment
      interferes with the performance benefits associated with practice.

PMID- 18077137
TI  - No association between psychometrically-determined schizotypy and olfactory
      identification ability in first-degree relatives of patients with schizophrenia
      and non-psychiatric controls.
AB  - OBJECTIVE: This study examined potential associations between schizotypy-
      including positive, negative, and disorganized domains--and olfactory
      identification ability. Based on a prior report (Park, S., Schoppe, S., 1997.
      Olfactory identification deficit in relation to schizotypy. Schizophr. Res. 26,
      191-197), it was hypothesized that positive and negative schizotypy would be
      associated with poorer olfactory identification ability, at least among male
      participants. METHOD: As part of a larger study, the Schizotypal Personality
      Questionnaire (SPQ) and University of Pennsylvania Smell Identification Test
      (UPSIT) were administered to 98 participants, including 44 healthy first-degree
      relatives of individuals with schizophrenia and related disorders and 54 non
      psychiatric controls. Potential associations between SPQ subscales and UPSIT
      score were examined while considering the effects of sociodemographic variables
      on these measures. RESULTS: SPQ and UPSIT scores were not significantly different
      in first-degree relatives and controls. There was no evidence of an association
      between SPQ domains and UPSIT score, even when controlling for possible
      confounding variables, including age and educational attainment. CONCLUSIONS: The
      nascent literature on potential associations between schizotypy and olfactory
      identification ability has yielded mixed findings to date. The current study does
      not support a correlation between these two markers, and this lack of association
      -in addition to equal olfactory identification performance in relatives and
      controls--casts doubt on the utility of the UPSIT as a measure of an
      endophenotypic trait. Future research would benefit from larger, more diverse
      samples; the addition of objective, interviewer-based measures of schizotypy; and
      attention to potentially confounding sociodemographic variables.

PMID- 18077138
TI  - Concordance of patient and clinical ratings of symptom severity and change of
      psychotic illness.

PMID- 18077140
TI  - PPAR gamma is an important transcription factor in 1 alpha,25-dihydroxyvitamin D3
      induced involucrin expression.
AB  - BACKGROUND: 1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25(OH)2D3), the active form
      of vitamin D, suppresses keratinocyte proliferation, promotes keratinocyte
      differentiation, and induces involucrin expression. Peroxisome proliferation
      activated receptors (PPARs) are ligand-activated transcription factors. It has
      been reported that PPARs stimulate keratinocyte differentiation and regulate the
      expression of differentiation molecules. OBJECTIVE: Keratinocytes treated with 1
      alpha,25(OH)2D3 induced PPAR gamma, which was followed by increased involucrin
      expression. In this study, we investigated whether PPAR gamma is involved in the
      1 alpha,25(OH)2D3-induced involucrin expression in human keratinocytes. METHODS:
      Subconfluent keratinocytes were treated with 10(-7)M 1 alpha,25(OH)2D3 for the
      indicated times, and PPAR and involucrin mRNA expression were determined by real
      time RT-PCR. The levels of PPARs, involucrin, p38, and phospho-p38 proteins were
      assayed by Western blotting, and the DNA binding activities of PPAR gamma and AP
      1 were investigated by electrophoretic mobility shift assays (EMSA). To examine
      the role of PPAR gamma in 1 alpha,25(OH)2D3 responses, recombinant adenovirus
      carrying a dominant-negative form of PPAR gamma (Axdn-PPAR gamma) was constructed
      and transfected into keratinocytes. The p38 inhibitor SB203580 was added to the
      cultures to evaluate the involvement of p38 in involucrin expression. RESULTS: 1
      alpha,25(OH)2D3 induced PPAR gamma expression and stimulated PPAR gamma activity.
      The introduction of dn-PPAR gamma inhibited the expression of involucrin mRNA and
      protein induced by 1 alpha,25(OH)2D3, and suppressed AP-1 DNA binding activity. 1
      alpha,25(OH)2D3 also triggered the phosphorylation of p38, which contributes to
      involucrin induction. Moreover, dn-PPAR gamma prevented the 1 alpha,25(OH)2D3
      induced phosphorylation of p38. CONCLUSIONS: These results suggest that PPAR
      gamma regulates involucrin expression by controlling the AP-1 signal and p38
      activation in 1 alpha,25(OH)2D3-induced keratinocyte differentiation.

PMID- 18077139
TI  - Glutamate agonists for schizophrenia stimulate dopamine D2High receptors.

PMID- 18077141
TI  - An outbreak of carbapenem-resistant Acinetobacter baumannii producing OXA-23
      carbapenemase in western China.
AB  - Twenty-two non-repetitive carbapenem-resistant Acinetobacter baumannii isolates
      were obtained from Intensive Care Unit patients. All of the isolates carried
      bla(OXA-23), bla(OXA-66), a novel cephalosporinase-encoding gene (bla(ADC-25))
      and a class 1 integron with an aacC1-orfP-orfQ-aadA1a cassette array and had
      identical enterobacterial repetitive intergenic consensus (ERIC) profiles. ISAba1
      was found upstream of bla(OXA-23), but was not associated with bla(OXA-66) or
      bla(ADC-25).

PMID- 18077142
TI  - Striatal dopamine D2 receptor binding and dopamine release during cue-elicited
      craving in recently abstinent opiate-dependent males.
AB  - Opiate addiction is a chronic disorder characterized by relapse behaviour, often
      preceded by craving and anhedonia. Chronic craving and anhedonia have been
      associated with low availability of dopamine D2 receptors (D2Rs) and cue-elicited
      craving has been linked with endogenous dopamine release. We studied D2R
      availability and cue-elicited endogenous dopamine release in 12 abstinent opiate
      dependent males and 18 age-matched male controls with [123I]IBZM SPECT. Craving
      was manipulated with a video containing heroin-related stimuli. Moreover, chronic
      craving, anhedonia and cue-elicited craving were measured. We found lower
      baseline D2R availability in opiate-dependent subjects than controls in the left
      caudate nucleus. D2R availability in the putamen correlated negatively with years
      of opiate use. Opiate-dependent subjects demonstrated higher dopamine release
      after cue-exposure in the right putamen than controls. Chronic craving and
      anhedonia were positively correlated with DA release. Treatment strategies that
      increase D2Rs may, therefore, be an interesting approach to prevent relapse in
      opiate addiction.

PMID- 18077143
TI  - Identity, origin, and migration of peripheral glial cells in the Drosophila
      embryo.
AB  - Glial cells are crucial for the proper development and function of the nervous
      system. In the Drosophila embryo, the glial cells of the peripheral nervous
      system are generated both by central neuroblasts and sensory organ precursors.
      Most peripheral glial cells need to migrate along axonal projections of motor and
      sensory neurons to reach their final positions in the periphery. Here we studied
      the spatial and temporal pattern, the identity, the migration, and the origin of
      all peripheral glial cells in the truncal segments of wildtype embryos. The
      establishment of individual identities among these cells is reflected by the
      expression of a combinatorial code of molecular markers. This allows the
      identification of individual cells in various genetic backgrounds. Furthermore,
      mutant analysis of two of these marker genes, spalt major and castor, reveal
      their implication in peripheral glial development. Using confocal 4D microscopy
      to monitor and follow peripheral glia migration in living embryos, we show that
      the positioning of most of these cells is predetermined with minor variations,
      and that the order in which cells migrate into the periphery is almost fixed. By
      studying their lineages, we uncovered the origin of each of the peripheral glial
      cells and linked them to identified central and peripheral neural stem cells.

PMID- 18077144
TI  - Drosophila Follistatin exhibits unique structural modifications and interacts
      with several TGF-beta family members.
AB  - Follistatin (FS) is one of several secreted proteins that modulate the activity
      of TGF-beta family members during development. The structural and functional
      analysis of Drosophila Follistatin (dFS) reveals important differences between
      dFS and its vertebrate orthologues: it is larger, more positively charged, and
      proteolytically processed. dFS primarily inhibits signaling of Drosophila Activin
      (dACT) but can also inhibit other ligands like Decapentaplegic (DPP). In
      contrast, the presence of dFS enhances signaling of the Activin-like protein
      Dawdle (DAW), indicating that dFS exhibits a dual function in promoting and
      inhibiting signaling of TGF-beta ligands. In addition, FS proteins may also
      function in facilitating ligand diffusion. We find that mutants of daw are
      rescued in significant numbers by expression of vertebrate FS proteins. Since two
      PiggyBac insertions in dfs are not lethal, it appears that the function of dFS is
      non-essential or functionally redundant.

PMID- 18077145
TI  - Enhanced antioxidant bioactivity of Salvia miltiorrhiza (Danshen) products
      prepared using nanotechnology.
AB  - The traditional Chinese medicine, Salvia miltiorrhiza (Danshen), promotes blood
      circulation and relieves blood stasis, also demonstrating good antioxidant
      activity. In the present study, therefore, the antioxidant activities of
      medicinal plant materials prepared using nanotechnology or traditional grinding
      methods were compared using three biological assays. It was found that the
      nanotechnology preparation had stronger antioxidant bioactivities. Complementary
      quantitative analysis of four active constituents, salvianolic acid B,
      cryptotanshinone, tanshinone I and tanshinone IIA, by HPLC revealed only marked
      differences for salvianolic acid B. The results indicate that the polar active
      constituent in the nanotechnology samples was released faster compared to the
      traditionally powdered samples.

PMID- 18077146
TI  - Informed consent to opioid agonist maintenance treatment: recommended ethical
      guidelines.
AB  - BACKGROUND: Some bioethicists have questioned whether opioid addicted individuals
      are able to provide free and informed consent to opioid agonist maintenance
      treatment. Conflicting motives for providing such treatment (e.g. improving the
      personal health of addicts and protecting public health and order) can also
      influence what individuals are required to consent to, and how that consent is
      obtained. We discuss both issues and attempt to specify the conditions for
      obtaining informed consent to agonist maintenance treatment for opioid addiction.
      METHODS: We briefly review the neuroscientific literature on the effects of
      addiction on the autonomy and decision-making capacity of opioid dependent
      individuals, and ascertain how informed consent to the treatment of opioid
      addiction should be obtained. We also provide an ethical analysis of the
      competing social and medical forces that influence the consent process and make
      some recommendations on how to ensure that individuals enter maintenance
      treatment that is provided in an effective and ethical way. RESULTS: Our analysis
      shows that whilst the autonomy of opioid dependent individuals is impaired by
      their addiction, they do retain the ability to consent to treatment provided they
      are not in acute withdrawal or intoxication. These symptoms should have abated,
      either by supervised withdrawal or stabilisation on agonist maintenance, before
      they are asked to consent to a detailed treatment contract. Once stabilised,
      individuals should be provided with detailed information about the risks and
      benefits of all treatments, and restrictions and regulations under which they are
      provided. CONCLUSION: Informed consent is an important part of the treatment
      process that should be obtained in ways that increase the autonomy and decision
      making capacity in opioid addicts.

PMID- 18077147
TI  - Electrochemical fabrication and evaluation of highly sensitive nanorod-modified
      electrodes for a biotin/avidin system.
AB  - Bioaffinity sensors need to be rapid, specific, and highly sensitive. To realize
      these features, electrodes that can elicit high electrochemical performance are
      necessary. In this study, we developed nanorod array electrode and performed
      cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS)
      experiments to study the interfacial properties of the nanorod array electrode
      with Fe(CN)(6)(3-/4-) as the redox molecules. Results showed that both the CV and
      EIS measurements captured very well the resistive and capacitive changes due to
      the adsorption of functionalizing molecules and the coupling between avidin and
      biotin. The EIS measurements were more sensitive in discriminating small changes
      caused by the surface adsorption of various molecules. The use of avidin
      functionalized gold nanorod modified electrodes had led to much increased
      detection sensitivity along with a detection-limit as low as 1 ng/mL of biotin.

PMID- 18077148
TI  - Sequential conversion by catalytically active MIP and immobilized tyrosinase in a
      thermistor.
AB  - To amplify the heat-signal generated by MIP catalyzed solvolysis of phenylacetate
      the reaction has been combined for the first time in a reactor with the
      subsequent oxidation by immobilized tyrosinase. The polymer cleaves the substrate
      and the released phenol is afterwards converted to o-benzoquinone by the
      tyrosinase. The separated and sequentially coupled reactions are characterized by
      the heat generated in a thermistor. The sequential substrate conversion results
      in a combined heat generation which results a five times higher signal than
      compared to the polymer alone.

PMID- 18077149
TI  - Current based antibodies detection from human serum enhanced by secondary
      antibodies labelled with gold nanoparticles immobilized in a nanogap.
AB  - We present the electrical detection of immunoglobulin G (IgGs) from human serum
      using a nanogap-based biosensor. The detection method is based on the capture of
      IgGs by a probe immobilized between gold nanoelectrodes of 30-90nm spacing. The
      captured IgGs are further reacted with secondary antibodies labelled with gold
      nanoparticles (GNPs). Insertion of GNPs into the nanogap resulted in increasing
      the conductance through the nanogap. The use of a chip with 90 nanogaps enabled
      the calculation of a quality factor for the detection which, coupled with a non
      linear regression analysis of the data, easily discriminated specific and
      differential capture of human antibodies by arrayed probes. We obtained a 500
      fold higher quality factor with protein A compared to goat anti-murine
      antibodies. This method can be applied, through these proof-of-concept
      experiments, to the detection of protein-protein interactions in biological
      samples.

PMID- 18077150
TI  - Incidence and time trends of soft tissue sarcomas in German children 1985-2004 -
      a report from the population-based German Childhood Cancer Registry.
AB  - The incidence of soft tissue sarcoma (STS) in Europe is increasing, but it is
      unclear whether this increase can also be seen in Germany. We analysed the
      heterogeneous group of STS recorded to the German Childhood Cancer Registry
      (GCCR) between 1985 and 2004 with respect to incidence data. Age-specific, age
      standardised and cumulative incidence rates were calculated. Additionally, the
      average annual percent change (AAPC), derived from a Poisson regression model,
      was estimated, using time in years as the explanatory, continuous variable. Two
      thousand sixty-one children were diagnosed at a median age of 72 months. Most
      common are rhabdomyosarcomas (RMS) (n=1202) and fibrosarcomas (n=174). The age
      standardised incidence rate (ASR) is 0.9 per 100,000/year for all STS, 0.70 for
      rhabdomyosarcoma-like (n=1588) and 0.18 for non-rhabdomyosarcoma-like (n=411)
      STS. AAPC is +0.4% (95%-confidence interval [-0.4;+1.2%]) for STS. In Germany,
      the increase in incidence rate is less evident than in other European countries.

PMID- 18077151
TI  - Gene expression predicts differential capecitabine metabolism, impacting on both
      pharmacokinetics and antitumour activity.
AB  - Capecitabine is converted into 5'-deoxy-5-fluorocytidine (5'DFCR), 5'-deoxy-5
      fluorouridine (5'DFUR) and 5-fluorouracil (5-FU) by CES1 and 2, CDD, and TP, in
      both liver and tumour. 5-FU is catabolised by DPD. Gene expression analysis of
      these enzymes was undertaken in fresh human hepatocytes, mouse liver, colorectal
      cancer cell lines and xenografts. Cell lines with low CDD expression (<1.5) had
      5'DFCR/5'DFUR cytotoxicity ratios>2 and cell lines with TP/DPD<0.6 had 5'DFUR
      IC50>50 microM (SRB assay). A pharmacokinetic/pharmacodynamic study in nude mice
      bearing HCT 116 xenografts and treated with capecitabine by oral gavage assessed
      pharmacokinetic, gene expression and antitumour activity. Low liver CDD
      correlated with high 5'DFCR plasma concentrations in mice. CDD expression was
      approximately 100-fold higher in fresh human hepatocytes than mouse liver,
      explaining the higher plasma 5'DFUR concentrations reported previously in humans.
      Tumour 5-FU concentration correlated with TP/DPD and with tumour response. These
      studies identify the potential utility of gene expression analysis and drug
      monitoring in tumour in patients.

PMID- 18077152
TI  - Childhood cancer survival in France, 1990-1999.
AB  - The aim of this study was to describe the overall survival after childhood cancer
      in France using follow-up data from regional population-based registries. The
      survival of children (aged under 15 years) diagnosed with a cancer during 1990
      1999 was analysed. For all cancers, the survivals were, respectively, 90.3% [89.4
      91.3] at 1-year, 75.2% [73.8-76.6] at 5 years and 72.2% [70.7-73.7] at 10 years.
      During the 1990s, the average improvement in the 5-year survival was +1.2% per
      year. Adjusted for gender, age, area of residence and stage, children with cancer
      diagnosed between 1995 and 1999 had a 0.80 reduced risk of dying compared with
      those whose cancer had been diagnosed between 1990 and 1994. The increase of
      survival at the population level reflects a global improvement in childhood
      cancer care. The Paediatric Registries, in association with the French Society of
      Childhood Cancer, are now collecting data to quantify on a national basis the
      other events, at least relapse and second cancers.

PMID- 18077153
TI  - Educational inequalities in cancer mortality differ greatly between countries
      around the Baltic Sea.
AB  - OBJECTIVE: To compare educational inequalities in cancer mortality between
      Poland, Lithuania, Estonia, Finland and Sweden. METHODS: Data are either follow
      up or unlinked cross-sectional studies. The relative index of inequality (RII)
      and the slope index of inequality (SII) are calculated to express the magnitude
      of mortality differences according to educational level for all cancers and for
      specific cancers. RESULTS: Large educational inequalities in total cancer
      mortality were observed, particularly amongst men. Inequalities in upper aero
      digestive tract and lung cancer in men and cervix cancer in women were larger in
      Poland, Lithuania and Estonia, whereas inequalities in lung cancer in women were
      larger in Finland and Sweden. CONCLUSIONS: Countries of the Baltic Sea region
      differ strongly with regard to the magnitude and pattern of the educational
      inequalities in cancer mortality.

PMID- 18077154
TI  - The strength of European oncology.

PMID- 18077155
TI  - Organosolv pretreatment by crude glycerol from oleochemicals industry for
      enzymatic hydrolysis of wheat straw.
AB  - In order to defray the cost of biodiesel production, the ensuing work was to
      further investigate utilization of the crude glycerol (CG) from oleochemicals
      industry in the atmospheric autocatalytic organosolv pretreatment (AAOP) to
      enhance enzymatic hydrolysis. The AAOP-CG enabled wheat straw to achieve with
      reasonable enzymatic hydrolysis yields, reaching 75% for the wet substrate and
      63% for the dried. Lipophilic compounds from the CG formed pitch deposition on
      the fiber, which was responsible for low delignification (30%) and also
      troublesome in practical operation. Pitch deposits itself had no significant role
      on enzymatic hydrolysis. A striking finding of the lignin recondensation and/or
      lignin-carbohydrate complex helped explain why dried pretreated wheat straw had a
      low enzymatic hydrolysis yield. The CG was suitable for the AAOP to enhance
      enzymatic hydrolysis of lignocellulosic biomass. But it was advisable to remove
      lipophilic compounds from crude glycerol before utilization.

PMID- 18077156
TI  - Changes in nitrogen isotopic compositions during composting of cattle feedlot
      manure: effects of bedding material type.
AB  - Temporal changes in delta(15)N of cattle feedlot manure during its composting
      with either rice hull (RHM) or sawdust (SDM) as bedding materials were
      investigated. Regardless of the bedding material used, the delta(15)N of total N
      in the manure increased sharply from +7.6 per thousand to +9.9 per thousand and
      from +11.4 per thousand to +14.3 per thousand, respectively, in RHM or SDM,
      within 10 days from the commencement of composting. Such increases could be
      attributed primarily to N loss via NH(3) volatilization and denitrification based
      on the very high delta(15)N values (greater than +20 per thousand) of NH(4)(+)
      and NO(3)(-) in the co-composted manure. The delta(15)N of total N in RHM was
      substantially lower (by more than 3 per thousand) than that in SDM, suggesting
      that the delta(15)N of the composted manure was affected not only by N loss but
      also by the type of bedding material used. Specifically, the higher N
      concentration in the rice hull than in the saw dust could lead to a greater (15)N
      isotope dilution.

PMID- 18077157
TI  - The potential applications of using compost chars for removing the hydrophobic
      herbicide atrazine from solution.
AB  - One commercial compost sample was pyrolyzed to produce chars as a sorbent for
      removing the herbicide atrazine from solution. The sorption behavior of compost
      based char was compared with that of an activated carbon derived from corn
      stillage. When compost was pyrolyzed, the char yield was greater than 45% when
      heated under air, and 52% when heated under N(2). In contrast, when the corn
      stillage was pyrolyzed under N(2), the yield was only 22%. The N(2)-BET surface
      area of corn stillage activated carbon was 439 m(2)/g, which was much greater
      than the maximum compost char surface area of 72 m(2)/g. However, the sorption
      affinity of the compost char for dissolved atrazine was comparable to that of the
      corn stillage activated carbon. This similarity could have resulted from the
      initial organic waste being subjected to a relatively long period of thermal
      processes during composting, and thus, the compost was more thermally stable when
      compared with the raw materials. In addition, microorganisms transformed the
      organic wastes into amorphous humic substances, and thus, it was likely that the
      microporisity was enhanced. Although this micropore structure could not be
      detected by the N(2)-BET method, it was apparent in the atrazine sorption
      experiment. Overall, the experimental results suggested that the compost sample
      in current study was a relatively stable material thermally for producing char,
      and that it has the potential as a feed stock for making high-quality activated
      carbon.

PMID- 18077158
TI  - Comparison between two policy strategies for scheduling trucks in a biomass
      logistic system.
AB  - Approximately 75% of the cost to load, haul, and deliver a weekly supply of
      herbaceous biomass from temporary storage locations near the production fields to
      a bioprocessing plant (50Mg/h average capacity, 24/7 operation) is truck cost.
      The management policy that a bioprocessing plant uses to schedule trucks
      determines the maximum number of trucks required, and thereby, the total cost for
      the logistic system. Three land use rates corresponding to 50%, 45%, and 40% of
      existing pastureland within a 3.2-km radius of chosen satellite storage locations
      were used to establish a production base surrounding the plant location. Total
      area harvested was 25,500 ha, or about 2.1% of the total land area in the 7
      county region studied. Assumed average yield was 8.3Mg/ha. Two different
      management policies, one based on travel time (Policy 1) and another based on the
      assignment of trucks to given sectors of the surrounding production base (Policy
      2) were used to develop truck schedules. The logistic system was modeled as a
      discrete event simulation model, and the schedule was validated. The maximum
      number of trucks needed for the logistic system was 32, 33 and 34 for 50%, 45%
      and 40% land use rates, respectively. In Policy 1, the maximum number of loads
      accumulated in the at-plant inventory was 384 truckloads at 50% land use rate
      (maximum inventory corresponds to about 3 days of plant operation). In Policy 2,
      the maximum number of loads accumulated in the at-plant inventory was 330
      truckloads at 50% land use rate. Total number of loader and unloader operating
      hours for both the policies was computed, and the loader and unloader utilization
      rates were 83.5% and 70.8%, respectively. The delivered cost (load, haul, and
      unload) varied from USD14.68 (Policy 1) to USD16.14 per Mg (Policy 2) for 15%
      w.b. moisture content biomass.

PMID- 18077160
TI  - In vitro SAR of pyrrolidine-containing histamine H3 receptor antagonists: trends
      across multiple chemical series.
AB  - Structure-activity relationships (SAR) were analyzed within a library of diverse
      yet simple compounds prepared as histamine H3 antagonists. The libraries were
      constructed with a variety of low molecular weight pyrrolidines, selected from
      (R)-2-methylpyrrolidine, (S)-2-methylpyrrolidine, and pyrrolidine.

PMID- 18077159
TI  - Structural analogs of tylophora alkaloids may not be functional analogs.
AB  - Phenanthroindolizidine-based tylophora alkaloids have been reported to have
      potential antitumor, anti-immuno and, anti-inflammatory activity. The structure
      activity relationships of a series of tylophora alkaloids were studied to guide
      future drug design. Our results indicate that although these compounds are
      structural analogs, their potency of cytotoxicity, selectivity against NF-kappaB
      signaling pathway, and their inhibitory effects against protein and nucleic acid
      synthesis are different. Because they do not have an identical spectrum of
      targets, the studied compounds are structural, but may not be functional analogs.

PMID- 18077161
TI  - Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a
      cell- and caspase-based HTS assay. Part 5: modifications of the 2- and 3
      positions.
AB  - As a continuation of our efforts to discover and develop apoptosis inducing 4
      aryl-4H-chromenes as novel anticancer agents, we explored modifications at the 2-
      and 3-positions. It was found that replacement of the 3-cyano group by an ester,
      including methyl and ethyl ester, resulted in >200-fold reduction of activity.
      Conversion of the 2-amino group into an amide or urea resulted in 4- to 10-fold
      drop of activity. Similarly, converting the 2-amino group into a hydrogen
      resulted in 4- to 10-fold reduction of activity. Compound 3d was highly active
      with an EC(50) value of 29 nM and a GI(50) value of 6 nM in T47D cells.
      Importantly, the 2-H analog 3d was found to be much more stable under acidic
      conditions compared to the 2-NH(2) analog 3b, suggesting that 2-H analogs might
      have better bioavailability than the 2-NH(2) analogs.

PMID- 18077162
TI  - 2-Oxo-tetrahydro-1,8-naphthyridines as selective inhibitors of malarial protein
      farnesyltransferase and as anti-malarials.
AB  - A new class of 2-oxo-tetrahydro-1,8-naphthyridine-based protein
      farnesyltransferase inhibitors were synthesized and found to inhibit protein
      farnesyltransferase from the malaria parasite with potencies in the low nanomolar
      range. The compounds were much less potent on mammalian protein
      prenyltransferases. Two of the compounds block the growth of malaria in culture
      with potencies in the sub-micromolar range. Some of the compounds were found to
      be much more metabolically stable than previously described tetrahydroquinoline
      based protein farnesyltransferase inhibitors.

PMID- 18077163
TI  - Conformationally constrained diketopimelic acid analogues as inhibitors of
      dihydrodipicolinate synthase.
AB  - Dihydrodipicolinate synthase (DHDPS) is a key enzyme in lysine biosynthesis and a
      potential antibiotic target. The enzyme catalyses the condensation of (S)
      aspartate semi-aldehyde (ASA) and pyruvate to form dihydrodipicolinate.
      Constrained diketopimelic acid derivatives have been designed as mimics of the
      acyclic enzyme-bound condensation product of ASA and pyruvate. Several of the
      compounds are shown to be active, slow-binding inhibitors with improved
      inhibition of DHDPS.

PMID- 18077164
TI  - Rapid novel divergent synthesis and muscarinic agonist profile of all four
      optical isomers of N,N,N-trimethyl(6-methyl-1,4-dioxan-2-yl)methanaminium iodide.
AB  - Two stereoselective parallel divergent four-step procedures to obtain all four
      enantiomeric forms of N,N,N-trimethyl(6-methyl-1,4-dioxan-2-yl)methanaminium
      iodide were developed. Enantiomeric purity was determined by quantitative (1)H
      NMR spectroscopy in the presence of the chiral shift reagent (+)-MTPA. The
      biological profile of the obtained compounds was evaluated at all muscarinic
      receptor subtypes by binding and functional assays.

PMID- 18077165
TI  - Anti-Pneumocystis carinii and antiplasmodial activities of primaquine-derived
      imidazolidin-4-ones.
AB  - A series of primaquine-derived imidazolidin-4-ones were screened for their in
      vitro activity against Pneumocystis carinii and Plasmodium falciparum W2 strain.
      Most compounds were active against P. carinii above 10 microg/mL and displayed
      slight to marked activity. The imidazolidin-4-ones most active against P. carinii
      were also those most active antiplasmodial agents, in the muM range. One of the
      tested imidazolidin-4-ones was slightly more active than the parent primaquine
      and may represent a lead compound for the development of novel anti-P. carinii 8
      aminoquinolines with increased stability and resistance to metabolic
      inactivation.

PMID- 18077166
TI  - Novel missense, insertion and deletion mutations in the neurotrophic tyrosine
      kinase receptor type 1 gene (NTRK1) associated with congenital insensitivity to
      pain with anhidrosis.
AB  - Hereditary sensory and autonomic neuropathy type IV (HSAN IV) or congenital
      insensitivity to pain with anhidrosis (CIPA) is an autosomal-recessive disorder
      affecting the neurotrophin signal transduction pathway. HSAN IV is characterized
      by absence of reaction to noxious stimuli, recurrent episodes of fever,
      anhidrosis, self mutilating behaviour and frequent mental retardation. Mutations
      in the neurotrophic tyrosine kinase receptor type 1 (NTRK1) are associated with
      this disorder. We investigated NTRK1 mutations in five HSAN IV patients and one
      less typical patient with hypohidrosis, insensitivity to pain as well as motor-
      and sensory deficits in the peripheral nervous system. For the HSAN IV patients
      we identified a homozygous missense mutation (p.I572S), a homozygous deletion of
      1985bp (g.7335164-7336545del), a homozygous insertion c.722_723insC in exon 7 and
      two compound heterozygous mutations (p.Q558X+p.L717R). The less typical patient
      as well as one HSAN IV patient revealed no NTRK1 mutation.

PMID- 18077167
TI  - X-linked myotubular myopathy and chylothorax.
AB  - X-linked myotubular myopathy usually presents at birth with hypotonia and
      respiratory distress. Phenotypic presentation, however, can be extreme variable.
      We report on a newborn baby, who presented with the severe form of the disease.
      In the second week of life, he developed a clinically relevant chylothorax,
      needing drainage and treatment with octreotide acetate. Pleural effusions are
      frequently described in patients with congenital myotonic dystrophy. To our
      knowledge, the association of chylothorax and X-linked myotubular myopathy has
      not been described to date. As chylothorax could not be attributed to any evident
      condition in this child, perhaps it may be added to the clinical spectrum of X
      linked myotubular myopathy.

PMID- 18077168
TI  - Effectively nursing patients receiving aromatase inhibitor therapy.
AB  - Inhibiting estrogen production is a common means of preventing breast cancer
      recurrence. The aromatase inhibitors (AIs) are becoming the preferred treatment
      over tamoxifen as adjuvant therapy for postmenopausal women with hormone
      sensitive early breast cancer. Like all adjuvant therapies, AIs have adverse
      events (AEs) associated with their use, many of which resemble symptoms common to
      menopause. Because of the greater efficacy of AIs in preventing breast cancer
      recurrence over tamoxifen, these AEs may be considered tolerable by many patients
      and often can be effectively managed and/or prevented. Educating patients about
      anticipated AEs may help them understand, accept, and cope with these AEs. This
      article reviews the AEs associated with different adjuvant AI treatments and
      highlights some strategies to manage them effectively. It also highlights the
      importance of patient education regarding AI therapy and involvement in treatment
      decisions, which may lead to better long-term adherence and ultimately to better
      outcomes.

PMID- 18077169
TI  - The daily job of night killers: alternative roles of the BCL-2 family in
      organelle physiology.
AB  - Apoptosis is essential for maintenance of tissue homeostasis and its deregulation
      underlies many disease conditions. The BCL-2 family of proteins is a group of
      evolutionarily conserved regulators of cell death, comprising both anti- and pro
      apoptotic members, which operate at the mitochondrial membrane to control caspase
      activation. Different BCL-2-related proteins are also located in multiprotein
      complexes at the endoplasmic reticulum (ER), which are involved in the control of
      diverse cellular processes, including calcium homeostasis, autophagy, the
      unfolded protein response and ER morphogenesis. Here, we describe the emerging
      concept that BCL-2-related proteins have alternative functions beyond apoptosis
      to control the essential functions of the cell.

PMID- 18077170
TI  - Tibial slope and patellar height after opening wedge high tibia osteotomy using
      autologous tricortical iliac bone graft.
AB  - Our aim was to evaluate the alteration in angle of posterior slope of the tibia
      and the degree of patellar height following medial opening wedge high tibia
      osteotomy(HTO) using autologous tricortical iliac bone graft in 32 consecutive
      patients. Twenty three females and nine males underwent medial opening wedge high
      tibia osteotomy (HTO) using autologous tricortical iliac bone graft in 34 knees
      (33 primary medial compartment osteoarthritis and 1 idiopathic osteonecrosis of
      medial tibial condyle). The posterior slope of tibia was determined by the
      proximal tibial anatomical axis. Patellar height was measured by the Insall
      Salvati and the Blackburne-Peel ratios. Preoperative and postoperative (last
      follow up) values of these three parameters were compared. The intra- and
      interobserver variability of these methods was determined before and after
      operation. At the end of mean follow up of 3 years this procedure produced no
      significant change in posterior slope. Pre and postoperative posterior slope were
      8.7 degrees+/-3.6 degrees and 8.2 degrees+/-2.8 degrees respectively (P=0.412).
      Pre and postoperative Insall-Salvati ratios were 0.93+/-0.10 and 1.05+/-0.11
      respectively (P<0.001). The Insall-Salvati ratio increased in 94% of patients and
      patellar ligament length was significantly increased. The distance between the
      patellar and tibiofemoral joint line decreased in 82% of patients. The mean
      Blackburne-Peel ratio declined from 0.71+/-0.12 to 0.61+/-0.13 (P<0.001). Twenty
      six percent of postoperative Blackburne-Peel values satisfied the radiographic
      criterion for patellar infera (Blackburne-Peel ratio<0.54). There was no
      difference in the intra-and interobserver variability of measurements either
      before or after HTO. Opening wedge HTO using autologous tricortical iliac bone
      graft with internal fixation and early mobilisation prevented change in posterior
      slope of tibia, lengthened the patellar ligament and elevated the tibiofemoral
      joint line when the mean ratio of anterior and posterior gap at the osteotomy
      site was around two-thirds.

PMID- 18077171
TI  - 1,3-Dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives as highly
      potent and selective human A(2B) adenosine receptor antagonists.
AB  - A new series of 1,3-dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine
      derivatives has been identified as potent A(2B) adenosine receptor antagonists.
      The products have been evaluated for their binding affinities for the human
      A(2B), A(1), A(2A), and A(3) adenosine receptors. N-(4-chloro-phenyl)-2-[3-(2,6
      dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-5-methyl-pyrazol-1-yl] (11c)
      showed a high affinity for the human A(2B) adenosine receptor K(i)=7nM and good
      selectivity (A(1), A(2A), A(3)/A(2B)>140). Synthesis and SAR of this novel class
      of compounds is presented herein.

PMID- 18077172
TI  - Synthesis and anticonvulsant evaluation of N-substituted isoquinoline AMPA
      receptor antagonists.
AB  - In our previous studies a ligand-based approach led to the identification of
      noncompetitive AMPA receptor antagonists containing isoquinoline scaffold. In an
      attempt to perform a systematic SAR study, we synthesized new N-substituted
      isoquinolines bearing the most salient features described by our 3D pharmacophore
      model. All compounds were screened against audiogenic seizures and some
      derivatives showed anticonvulsant properties. Compound 24, the most active of the
      series, was also tested in vitro using the patch-clamp technique and proved to
      antagonize AMPA-mediated effects.

PMID- 18077173
TI  - Synthesis and biological evaluation of pyrroloiminoquinone derivatives.
AB  - Synthesis of 10 pyrroloiminoquinone derivatives is presented. The strategy is
      based around the elaboration of a common intermediate by reaction with primary
      amines. All the compounds obtained have been subjected to antiproliferative
      activity with three different cell lines (NCI-H460, HeLa, and HL-60). The
      capacity of 4 selected compounds to affect the enzymatic activity of the nuclear
      enzyme DNA topoisomerase II and to form the typical DNA fragmentation which
      occurs in the apoptotic process is discussed here.

PMID- 18077174
TI  - Discovery of sulfonylalkylamides: A new class of orally active factor Xa
      inhibitors.
AB  - Factor Xa (FXa) is a trypsin-like serine protease involved in the coagulation
      cascade and has received great interest as a potential target for the development
      of new antithrombotic agents. Most of amidine-type FXa inhibitors reported have
      been found to show extremely poor oral bioavailability. Compound 1 is one of the
      first reported non-amidine type FXa inhibitors. To discover novel and orally
      active FXa inhibitors, we investigated flexible linear linkers between the 6
      chloronaphthalene ring and the 1-(pyridin-4-yl)piperidine moiety of 1 and found
      the orally active sulfonylalkylamide 2f with an FXa IC(50) of 0.05 microM,
      comparable with that of 1. Further modification to reduce the CYP3A4 inhibitory
      activity of 2f resulted in the potent, selective, and orally active 2
      methylpyridine analogue 2s (FXa IC(50) of 0.061 microM), for which the liability
      of CYP3A4 inhibition was significantly weakened compared to 2f. Compound 2s also
      showed long lasting anticoagulant activity in cynomolgus monkeys.

PMID- 18077175
TI  - Synthesis of novel oxazolidinone antimicrobial agents.
AB  - The oxazolidinone class of antimicrobials represents a promising advance in the
      fight against resistant Gram-positive bacterial infections. Four novel
      oxazolidinone antimicrobial compounds, each containing a benzodioxin ring system,
      have been prepared. The general synthesis of each compound begins with the
      construction of a benzodioxin ring system containing a nitro substituent that
      ultimately becomes the nitrogen of the oxazolidinone ring. Three of the compounds
      utilize high yielding 'click chemistry' in their final step. The antimicrobial
      activities of the new oxazolidinones have been measured and the MIC against
      Staphylococcus aureus for one of the antimicrobials was determined to be 2-3
      microg/mL, which is comparable to the well-known oxazolidinone, linezolid.

PMID- 18077177
TI  - Pulmonary endarterectomy is possible and effective without the use of complete
      circulatory arrest--the UK experience in over 150 patients.
AB  - OBJECTIVE: Pulmonary endarterectomy is the best treatment for patients with
      chronic thromboembolic pulmonary hypertension. Traditionally pulmonary
      endarterectomy has been performed utilising deep hypothermic circulatory arrest
      to provide a bloodless field, but some recent reports have challenged this
      concept. We reviewed our experience with selective antegrade cerebral perfusion
      as the initial strategy of controlling bronchial collateral flow to avoid
      complete circulatory arrest in patients undergoing pulmonary endarterectomy.
      METHODS: A retrospective review of all patients meeting the above criteria
      between July 2003 and June 2006. Selective antegrade cerebral perfusion at 20
      degrees C was used as the initial means of reducing blood flow to the operative
      field. RESULTS: One hundred and fifty-one patients (83 male, 68 female, mean age
      56+/-16 years) were operated on using this strategy. The preoperative New York
      Heart Association class distribution showed the majority to be in class III or IV
      (142 of 151). At initial assessment, mean pulmonary artery pressure was 49+/-12
      mmHg and mean pulmonary vascular resistance was 851+/-391 dynes s cm(-5).
      Selective antegrade cerebral perfusion was required in 145 for a total period of
      63+/-24 min. Thirteen (9%) patients required conversion to deep hypothermic
      arrest for completion of the operation. In-hospital mortality was 22 (15%). There
      were no instances of focal neurological deficit. Prearranged clinical follow-up
      for 3 and 12 months was 97% complete with one late death by 3 months and one more
      by 12 months. The majority were in New York Heart Association class I or II at 3
      months (102 of 115) and 12 months (65 of 74). At 3-month follow-up the mean
      pulmonary artery pressure was 27+/-10 mmHg and pulmonary vascular resistance was
      304+/-220 dynes s cm(-5). CONCLUSIONS: Overall results improved with era and
      institutional experience. The use of selective antegrade cerebral perfusion for
      pulmonary endarterectomy appears to be technically feasible in the majority of
      patients and is an alternative to complete circulatory arrest. To clarify its
      role further, comparison with deep hypothermic circulatory arrest in a randomised
      controlled trial is necessary.

PMID- 18077176
TI  - Loss of phospholipid asymmetry and elevated brain apoptotic protein levels in
      subjects with amnestic mild cognitive impairment and Alzheimer disease.
AB  - Oxidative stress, a hallmark of Alzheimer disease (AD), has been shown to induce
      lipid peroxidation and apoptosis disrupting cellular homeostasis. Normally, the
      aminophospholipid phosphatidylserine (PtdSer) is asymmetrically distributed on
      the cytosolic leaflet of the lipid bilayer. Under oxidative stress conditions,
      asymmetry is altered, characterized by the appearance of PtdSer on the outer
      leaflet, to initiate the first stages of an apoptotic process. PtdSer asymmetry
      is actively maintained by the ATP-dependent translocase flippase, whose function
      is inhibited if covalently bound by lipid peroxidation products, 4-hydroxynonenal
      (HNE) and acrolein, within the membrane bilayer in which they are produced.
      Additionally, pro-apoptotic proteins Bax and caspase-3 have been implemented in
      the oxidative modification of PtdSer resulting in subsequent asymmetric collapse,
      while anti-apoptotic protein Bcl-2 has been found to prevent this process. The
      current investigation focused on detection of PtdSer on the outer leaflet of the
      bilayer in synaptosomes from brain of subjects with AD and amnestic mild
      cognitive impairment (MCI), as well as expression levels of apoptosis-related
      proteins Bcl-2, Bax, and caspase-3. Fluorescence and Western blot analysis
      suggest PtdSer exposure on the outer leaflet is significantly increased in brain
      from subjects with MCI and AD contributing to early apoptotic elevation of pro-
      and anti-apoptotic proteins and finally neuronal loss. MCI is considered a
      possible transition point between normal cognitive aging and probable AD. Brain
      from subjects with MCI is reported to have increased levels of tissue oxidation;
      therefore, the results of this study could mark the progression of patients with
      MCI into AD. This study contributes to a model of apoptosis-specific oxidation of
      phospholipids consistent with the notion that PtdSer exposure is required for
      apoptotic-cell death.

PMID- 18077178
TI  - The xanthophyll cycle pigments in Secale cereale leaves under combined Cd and
      high light stress conditions.
AB  - Leaves of Secale cereale seedlings were exposed to high light illumination
      (1200micromolm(-2)s(-1)) and Cd ions at 5 or 50microM concentrations. Influence
      of these stress factors on violaxanthin cycle pigments content was analysed
      chromatographically. Chlorophyll a fluorescence induction was used to analyse
      response of PSII to stress conditions and contribution of light-harvesting
      complex (LHCII) in non-photochemical quenching of excitation energy. The Cd
      induced all-trans violaxanthin isomerization was analysed by HPLC technique in
      acetonitrile:methanol:water (72:8:3, v/v) solvent mixture. Interestingly, in the
      control and Cd-treated leaves subjected to high light, photochemical utilization
      of absorbed energy increased. This indicates plant adaptation to high light
      stress. In control plants high light caused zeaxanthin formation, however, the
      presence of Cd in the nutrient solution resulted in reduction of the second step
      of violaxanthin de-epoxidation process and anteraxanthin accumulation. In this
      study we have also shown, that non-photochemical quenching can be independent of
      anteraxanthin and zeaxanthin content. The particular increase in the cis isomers
      fraction in Cd-treated leaves has been explained in terms of a direct metal
      pigment interaction as confirmed by Cd-induced all-trans violaxanthin
      isomerization in organic solvent, leading to formation of 13-cis, 9-cis and 15
      cis isomers.

PMID- 18077179
TI  - Photodissociation of non-covalent peptide-crown ether complexes.
AB  - Highly chromogenic 18-crown-6-dipyrrolylquinoxaline coordinates primary amines of
      peptides, forming non-covalent complexes that can be transferred to the gas-phase
      by electrospray ionization. The appended chromogenic crown ether facilitates
      efficient energy transfer to the peptide upon ultraviolet irradiation in the gas
      phase, resulting in diagnostic peptide fragmentation. Collisional-activated
      dissociation and infrared multiphoton dissociation of these non-covalent
      complexes result only in their disassembly with the charge retained on either the
      peptide or crown ether, yielding no sequence ions. Upon UV photon absorption the
      intermolecular energy transfer is facilitated by the fast activation timescale of
      ultraviolet photodissociation (<10 ns) and by the collectively strong hydrogen
      bonding between the crown ether and peptide, thus allowing effective transfer of
      energy to the peptide moiety before disruption of the intermolecular hydrogen
      bonds.

PMID- 18077180
TI  - Evaluation of dicationic reagents for their use in detection of anions using
      positive ion mode ESI-MS via gas phase ion association.
AB  - Twenty-three different dications were investigated for their effectiveness in
      pairing with singly charged anions, thereby allowing the electrospray ionization
      mass spectrometry (ESI-MS) detection of anions as positively charged complexes.
      Nitrate, iodide, cyanate, monochloroacetate, benzenesulfonate, and perfluoro
      octanoate were chosen as representative test anions as they differ in mass, size
      to-charge ratio, chaotropic nature, and overall complexity. Detection limits were
      found using direct injection of the anion into a carrier liquid containing the
      dication. Detection limits are given for all six anions with each of the 23
      dications. Each anion was easily detected at the ppb (microg/L) and often the ppt
      (ng/L) levels using certain dicationic reagents. The ability of dicationic
      reagents to pair with anions and produce ESI-MS signals varied tremendously.
      Indeed, only a few dications can be considered broadly useful and able to produce
      sensitive results. Liquid chromatography (LC)-ESI-MS also was investigated and
      used to show how varying the dicationic reagent produced significantly different
      peak intensities. Also, the use of tandem mass spectrometry can lead to even
      greater sensitivity when using imidazolium based dications.

PMID- 18077181
TI  - Mass selective axial ion ejection from linear quadrupoles with added octopole
      fields.
AB  - Mass selective axial ejection of ions from linear quadrupoles with added octopole
      fields is described. Quadrupoles with 2.0% and 2.6% added octopole fields have
      been tested and compared with a conventional quadrupole. The effects of trapping
      ions at different q values, excitation voltage, scan direction, balanced and
      unbalanced rf voltages on the rods, and dc applied between the rods have been
      investigated. The highest scan speeds and best resolution are obtained with
      resonant excitation and ejection at high q (q = 0.8). With axial ejection, the
      quadrupole with a 2.0% added octopole field provides mass resolution and ejection
      efficiencies similar to a conventional rod set. Quadrupole, dipole, and
      simultaneous dipole-dipole excitation between the x and y rod pairs were
      compared, and no advantage was found with quadrupole or dipole-dipole excitation.
      The effects of scan speed were investigated and a resolution at half height of
      about 1600 is possible at scans speed up to 5000 Th/s.

PMID- 18077183
TI  - Efficient bacterial production of functional antibody fragments using a phagemid
      vector.
AB  - The so-called 'in vitro evolutionary method' using a phage display system has
      been applied for protein engineering of the antigen-binding fragment of
      antibodies (Fab) by conducting random mutagenesis at the antigen-binding site in
      combination with antigen-based biopanning. However, isolated phage clones
      displaying Fab cannot necessarily be used for efficient bacterial production of
      engineered Fab proteins, often due to deleterious defects in their proper folding
      abilities derived in compensation for the gain of high affinity for a particular
      antigen. We here report a new method of an efficient and direct bacterial
      expression system for the phagemid-coded Fab proteins without use of the helper
      phage. To overcome a low folding efficiency derived from somatic hypermutations,
      if any, we have established optimum conditions for bacterial cultivation and
      protein expression, utilizing unusually long cultivation time (>50 h) and very
      low temperature (25 degrees C) and thereby leading to the production and
      extracellular secretion of Fab proteins in a very high yield (3-15 mg/L of
      culture). The purified Fab folded correctly and could efficiently bind an
      antigen, as judged by circular dichroism and isothermal titration calorimetry,
      respectively.

PMID- 18077182
TI  - Lithium inhibits Smad3/4 transactivation via increased CREB activity induced by
      enhanced PKA and AKT signaling.
AB  - Smad proteins are intracellular transducers for transforming growth factor-beta
      (TGF-beta) signaling and play a critical role in differentiation, tissue repair
      and apoptosis of the central nervous system. Both TGF-beta and its regulated
      gene, plasminogen activator inhibitor type-1 (PAI-1), have been implicated in the
      etiology and progression of neurodegenerative diseases and mood disorders. We
      previously reported that GSK-3beta protein depletion suppresses Smad3/4-dependent
      gene transcription and causes a reduction in PAI-1 expression. Here, we provide
      evidence that lithium, the drug for the treatment and prophylaxis of bipolar
      disorder, inhibits Smad-dependent signaling by regulating cAMP-protein kinase A
      (PKA), AKT-glycogen synthase kinase-3beta (GSK-3beta), and CRE-dependent
      signaling pathways in neuron-enriched cerebral cortical cultures of rats. We
      demonstrate that lithium-induced activation of these pathways inhibits Smad3/4
      dependent gene transcription through an increase in pCREB(Ser133) protein levels,
      an enhanced interaction between pCREB(Ser133) and p300/CBP, which causes Smad3/4
      p300/CBP complex disruption and transcriptional suppression of Smad3/4-dependent
      genes. Therapeutic implications of our findings are discussed.

PMID- 18077184
TI  - Gender-dependent increases with healthy aging of the human cerebral cannabinoid
      type 1 receptor binding using [(18)F]MK-9470 PET.
AB  - The endocannabinoid system (ECS) is implicated as a regulator of homeostasis of
      several cerebral functions and is a novel target for drug treatment of
      neuropyschiatric disorders. So far, the cerebral cannabinoid-type 1 receptor
      (CB1R) has only been studied using in vitro, animal model, electrophysiological
      and post-mortem data. We have used positron emission tomography (PET) using a
      high-affinity, subtype-selective radioligand, [(18)F]MK-9470, to assess the in
      vivo cerebral CB1R distribution and its variation with healthy aging and gender.
      Fifty healthy volunteers (25 M/25 F, 18-69 years) underwent [(18)F]MK-9470 PET.
      Parametric [(18)F]MK-9470 binding maps were constructed, corrected for partial
      volume effects and analyzed using statistical parametric mapping in a combined
      categorical (gender) and covariate (age) design. We found that [(18)F]MK-9470
      binding to CB1R increased with aging but only in women (p(FWE)<0.05, corrected
      for multiple comparisons); this was most pronounced in the basal ganglia, lateral
      temporal cortex and limbic system, especially in the hippocampus. Men showed
      higher [(18)F]MK-9470 binding then women (p<0.001, uncorrected), in clusters of
      the limbic system and cortico-striato-thalamic-cortical circuit. Region-dependent
      and gender-related upregulation of [(18)F]MK-9470 binding with aging is in line
      with ex vivo findings in rodent studies and may be associated with a changing
      homeostatic capacity or compensation mechanisms in the ECS that is modulated by
      sex hormones. In vivo PET of the CB1R will likely improve our understanding of
      the ECS in several neurological and psychiatric disorders.

PMID- 18077185
TI  - Novel three-dimensional analysis tool for vascular trees indicates complete micro
      networks, not single capillaries, as the angiogenic endpoint in mice
      overexpressing human VEGF(165) in the brain.
AB  - To adequately supply tissues with oxygen and nutrients, the formation of
      functional vascular networks requires generation of normal, healthy vessels and
      their arrangement into an effective network architecture. While our knowledge
      about the development of single vessels significantly increased during the last
      years, mechanisms responsible for network formation are still poorly understood.
      This is probably due to the lack of suitable methods for quantification of
      structural properties of microvascular networks. Previously we showed that
      cerebral blood flow is not increased in mice exhibiting a 2- to 3-fold higher
      density of normal and perfused capillaries as a result of transgenic
      overexpression of the human vascular endothelial growth factor (VEGF(165)). Here
      we used vascular corrosion casting and hierarchical micro-computed tomography
      combined with a new network analysis tool to characterize the vascular
      architecture in gray and white matter of these mice. Our results indicate that
      VEGF overexpression leads to formation of additional micro-networks connected to
      higher order vessels rather than insertion of individual capillaries into the
      existing vessel structure. This implies that the smallest "angiogenic quantum",
      i.e. the final, stable result of angiogenesis and subsequent remodeling, is not a
      single microvessel, but a complete micro-network. In conclusion, high-resolution
      3D imaging combined with network analysis can substantially improve our
      understanding of vascular architecture, beneficial for the development of
      therapeutic angiogenesis as a clinical tool for applications such as wound
      healing or treatment of ischemic diseases.

PMID- 18077186
TI  - Network injury to pulvinar with neonatal arterial ischemic stroke.
AB  - The purpose of this study is to establish that newborn stroke involving extensive
      parts of cerebral cortex immediately leads to secondary network injury in
      pulvinar. Seven term infants with cortical stroke presented with hypersignal in
      pulvinar on DWI. Stroke types included: complete MCA stroke (n=4); PCA stroke,
      ICA stroke and multiple artery stroke (1 each). Age range at scanning was between
      day 2 and 6 after birth (except for 1 infant scanned within 7 days of acute
      presentation during ECMO). ADC values in secondarily injured pulvinar were
      significantly higher than in the area with primary (sub)cortical injury (all
      patients scanned with identical MR image acquisition). In the absence of asphyxia
      and because pulvinar is outside of the primary area of infarction, we conclude
      that there are suggestions from imaging for acute secondary injury to pulvinar
      following primary damage of their cortical targets and/or connecting axons. Acute
      secondary injury is probably due to excitotoxicity and deafferentiation. The
      relevance of network injury for prognosis and the impact of early treatment on it
      have yet to be studied, in stroke but also in other acute perinatal brain
      disorders.

PMID- 18077187
TI  - Deconvolution-based partial volume correction in Raclopride-PET and Monte Carlo
      comparison to MR-based method.
AB  - In this work, we evaluated three iterative deconvolution algorithms and compared
      their performance to partial volume (PV) correction based on structural imaging
      in brain positron emission tomography (PET) using a database of Monte Carlo
      simulated images. We limited our interest to quantitative radioligand PET
      imaging, particularly to (11)C-Raclopride and striatal imaging. The studied
      deconvolution methods included Richardson-Lucy, reblurred Van Cittert, and
      reblurred Van Cittert with the total variation regularization. We studied the
      bias and variance of the regional estimates of binding potential (BP) values and
      the accuracy of regional TACs as a function of the applied image processing. The
      resolution/noise tradeoff in parametric BP images was addressed as well. The
      regional BP values and TACs obtained by deconvolution were almost as accurate
      than those by structural imaging-based PV correction (GTM method) when the ideal
      volumes of interests (VOIs) were used to extract TACs from the images. For
      deconvolution methods, the ideal VOIs were slightly eroded from the exact
      anatomical VOI to limit the bias due to tissue fraction effect which is not
      corrected for by deconvolution-based methods. For the GTM method, the ideal VOIs
      were the exact anatomical VOIs. The BP values and TACs by deconvolution were less
      affected by segmentation and registration errors than those with the GTM-based PV
      correction. The BP estimates and TACs with deconvolution-based PV correction were
      more accurate than BPs and TACs derived without PV correction. The parametric
      images obtained by the deconvolution-based PV correction showed considerably
      improved resolution with only slightly increased noise level compared to the case
      with no PV correction. The reblurred Van Cittert method was the best of the
      studied deconvolution methods. We conclude that the deconvolution is an
      interesting alternative to structural imaging-based PV correction as it leads to
      quantification results of similar accuracy, and it is less prone to registration
      and segmentation errors than structural imaging-based PV correction. Moreover, PV
      corrected parametric images can be readily computed based on deconvolved dynamic
      images.

PMID- 18077188
TI  - Molecular phylogenetic relationships among species of the Malagasy-Comoran gecko
      genus Paroedura (Squamata: Gekkonidae).
AB  - We use approximately 3100bp of mitochondrial (ND2, ND4) and nuclear (RAG1,
      phosducin) DNA sequence data to recover phylogenetic relationships among 14 of
      the 16 recognized taxa of the lizard genus Paroedura as well as two undescribed
      forms. These geckos are endemic to Madagascar and the Comores and are popularly
      kept and bred by herpetoculturalists. The closest relative of Paroedura is
      another Indian Ocean leaf-toed gecko, Ebenavia. Both Bayesian inference and
      maximum parsimony strongly support the monophyly of two major clades within
      Paroedura that conflict with existing species group assignments based on scale
      characteristics. Our well-resolved tree elucidates a biogeographic pattern in
      which eastern Paroedura are most basal and western and south-western species form
      a monophyletic group. Our data demonstrate the phylogenetic utility of phosducin,
      a novel marker in squamate phylogenetics, at the intrageneric level.

PMID- 18077189
TI  - A randomised controlled trial of tidal irrigation vs corticosteroid injection in
      knee osteoarthritis: the KIVIS Study.
AB  - OBJECTIVES: Patients with knee osteoarthritis (OA) often suffer pain that is not
      fully controlled by analgesics and often require intra-articular therapies. The
      aim of this study was to compare the benefits of intra-articular corticosteroid
      injections (CSIs) and tidal irrigation (TI) in patients with OA of the knee.
      METHODS: We performed a dual-centre, single blind, randomised, parallel group
      trial comparing TI and CSI. Patients with knee OA were randomised to either
      irrigation using a 3.2mm arthroscope under local anaesthesia or an intra
      articular injection of 40 mg triamcinolone acetonide and 1% lidocaine. Patients
      were followed for 6 months. The primary outcome measure was the Western Ontario
      and McMaster Universities OA Index total pain score (visual analogue scale, VAS).
      RESULTS: One hundred and fifty patients were recruited of whom 71 received TI and
      79 CSI. In both treatment groups, over 80% of patients reported improvement at 2
      and 4 weeks. After this time, the benefit of CSI decreased whereas that of TI was
      maintained: at 26 weeks the pain relief afforded by TI was significantly greater
      than that of CSI. At 26 weeks 29% of the CSI group reported improvement vs 64% of
      the TI group (P<0.001). Patients with a knee effusion responded better to both
      treatments, however, this was most apparent for CSI. Patients with less severe
      radiographic OA also obtained the greatest improvement from both treatments.
      CONCLUSION: Both procedures lead to significant short-term pain relief of at
      least 4 weeks, however, TI displayed a significantly greater duration of benefit.
      Patients with effusions and milder radiographic change obtained the best response
      to treatment.

PMID- 18077190
TI  - Neonatal tactile stimulation enhances spatial working memory, prefrontal long
      term potentiation, and D1 receptor activation in adult rats.
AB  - Environmental stimuli during neonatal periods play an important role in the
      development of cognitive function. In this study, we examined the long-term
      effects of neonatal tactile stimulation (TS) on spatial working memory (SWM) and
      related mechanisms. We also investigated whether TS-induced effects could be
      counteracted by repeated short periods of maternal separation (MS). Wistar rat
      pups submitted to TS were handled and marked transiently per day during postnatal
      days 2-9 or 10-17. TS/MS pups were stimulated in the same way as TS pups and then
      individually separated from their mother for 1h/day. Their nontactile stimulated
      (NTS) siblings served as controls. In adulthood, TS and TS/MS rats showed better
      performance in two versions of the delayed alternation task and superior in vivo
      long-term potentiation of the hippocampo-prefrontal cortical pathway when
      compared with controls. Furthermore, there were more doses of A77636 (a selective
      dopamine D1 agonist) to significantly improve SWM performance in TS and TS/MS
      rats than in NTS rats, suggesting that activation of prefrontal D1 receptors in
      TS and TS/MS rats is more optimal for SWM function than in NTS rats. MS did not
      counteract TS-induced effects because no significant difference was found between
      TS/MS and TS animals. These data indicate that in early life, external tactile
      stimulation leads to long-term facilitative effects in SWM-related neural
      function.

PMID- 18077191
TI  - Impact on renal function after endovascular aneurysm repair with uncovered supra
      renal fixation assessed by serum cystatin C.
AB  - OBJECTIVE: Supra-renal fixation in endovascular aneurysm repair (SR-EVR) is used
      to improve the proximal seal of aortic stent grafts and appears to have minimal
      effect on serum creatinine. Serum cystatin C (CC) is a more sensitive marker of
      renal injury and, unlike creatinine, is unaffected by non-renal influence. The
      aim of this study was to assess the true renal effect of SR-EVR using this
      superior renal index. METHODS: Consecutive patients undergoing SR-EVR were
      prospectively recruited and compared to control groups undergoing open aneurysm
      repair (OR) and colorectal resection (CR). Serum CC and creatinine clearance
      (CrC) were determined pre-operatively and at 3, 6 and 12 months post-surgery.
      Renal function was compared using analyses of covariance (ANCOVA). RESULTS: Sixty
      five patients (M:F; 52:13, median age 74 years) were enrolled (24 SR-EVR, 28 OR,
      13 CR). Pre-operative renal function and risk factors were comparable (CC
      1.04mg/l, SR-EVR; 0.96mg/l, OR; 0.97mg/l, CR). Adjusting for baseline renal
      function, there was no significant difference in CC or CrC between study and both
      control groups at 3, 6 or 12-months post-operatively. CONCLUSION: Using cystatin
      C as a more sensitive renal index, there was no detectable evidence of kidney
      dysfunction at up to one-year following EVR with uncovered bare-metal supra-renal
      fixation.

PMID- 18077192
TI  - Infected upper extremity aneurysms: a review.
AB  - OBJECTIVES: To review the occurrence of mycotic aneurysm affecting upper
      extremity arteries. DESIGN: Literature review. MATERIALS AND METHODS: A MEDLINE
      search from 1950 until 2007 and an extensive manual search were carried out using
      bibliographies from relevant published papers including cases involving arteries
      distal to the subclavian. RESULTS: A total of 149 cases (68 papers) were
      identified. The brachial artery was the most frequently reported site, mostly
      associated with drug abuse, catheterization procedures or endocarditis. Since
      1950 arterial trauma (drug abuse or catheterization) was the commonest cause.
      Gram positive organisms were the most frequent microbes involved. Acknowledging a
      limited follow-up, most patients did well when surgical therapy was promptly
      instituted. CONCLUSIONS: Infected upper extremity aneurysms have been rarely
      described. IV drug abusers are a unique high-risk group for mycotic aneurysms in
      the upper extremities, most importantly in the axillary and brachial arteries.
      When rapidly performed, arterial ligation, primary repair or reconstruction with
      autogenous conduits was associated with favorable outcomes.

PMID- 18077193
TI  - Direct association between C-reactive protein serum levels and endothelial
      dysfunction in patients with claudication.
AB  - OBJECTIVES: To evaluate the relationship between C-Reactive Protein (hsCRP), a
      serum marker of inflammation, and endothelial dysfunction in patients with
      intermittent claudication. DESIGN, PATIENTS AND METHODS: Cross-sectional study
      with stratified sampling on dependent variables of age, genre, hypertension,
      hyperlipidemia, diabetes, smoking status and ankle-brachial index (ABI) to select
      156 patients from a target population of 4,100 patients with claudication. We
      assessed the flow-mediated arterial dilation (FMAD) as a reporter of endothelial
      function and plasma levels of hsCRP and fibrinogen. RESULTS: Patients with a
      FMAD<3% (range for the lowest 5% of healthy subjects) had increased levels of
      plasma hsCRP (6.3 vs 2.3mg/L; p<0.05) and fibrinogen (351vs 302mg/L; p<0.05) in
      comparison to those with FMAD>3%. There was a negative correlation between hsCRP
      and FMAD(r=-0.465; p<0.05). CONCLUSION: Impaired endothelial dysfunction is
      association with increased plasma concentrations of inflammatory markers, and
      both may have a role in the aetiopathogenesis of peripheral arterial disease.

PMID- 18077194
TI  - Cre recombinase expression controlled by the hematopoietic regulatory domain of
      Gata-1 is erythroid-specific.
AB  - Available data suggest that gene regulation by the Gata-1 Hematopoietic
      Regulatory Domain (Gata-1-HRD) is limited to cells derived from the erythroid
      lineage. This characteristic makes Gata-1-HRD a candidate for control of cre
      expression in conditional knock-in and knock-out models in which erythroid
      specific gene expression is essential. To characterize the specificity of Gata-1
      HRD regulation of cre, transgenic mice expressing improved cre recombinase (iCre)
      under the control of Gata-1-HRD were generated. The founders were crossbred with
      mice that have an inactive loxP-containing beta-galactosidase gene that can be
      rescued by the cre recombinase. The beta-galactosidase activity was detected in
      the marrow of this crossbred mouse, but no activity was observed in other organs.
      To identify the cre expressing cells in marrow, double-immunostaining of marrow
      sections with anti-beta-galactosidase, and antibodies against various
      hematopoietic lineage markers or erythropoietin receptor (epor) was performed.
      The epor positive cells in marrow expressed beta-galactosidase, but
      megakaryocytic precursors and nonerythroid epor-positive cells in brain and
      spleen did not. We conclude that when cre is under control of Gata-1-HRD, its
      expression/function is limited to erythroid progenitors. The knock-in and knock
      out models utilizing Gata-1-HRD-iCre, can be explored for the studies of
      erythroid-specific gene expression.

PMID- 18077195
TI  - The role of corneal crystallins in the cellular defense mechanisms against
      oxidative stress.
AB  - The refracton hypothesis describes the lens and cornea together as a functional
      unit that provides the proper ocular transparent and refractive properties for
      the basis of normal vision. Similarities between the lens and corneal crystallins
      also suggest that both elements of the refracton may also contribute to the
      antioxidant defenses of the entire eye. The cornea is the primary physical
      barrier against environmental assault to the eye and functions as a dominant
      filter of UV radiation. It is routinely exposed to reactive oxygen species (ROS)
      generating UV light and molecular O(2) making it a target vulnerable to UV
      induced damage. The cornea is equipped with several defensive mechanisms to
      counteract the deleterious effects of UV-induced oxidative damage. These comprise
      both non-enzymatic elements that include proteins and low molecular weight
      compounds (ferritin, glutathione, NAD(P)H, ascorbate and alpha-tocopherol) as
      well as various enzymes (catalase, glucose-6-phosphate dehydrogenase, glutathione
      peroxidase, glutathione reductase, and superoxide dismutase). Several proteins
      accumulate in the cornea at unusually high concentrations and have been
      classified as corneal crystallins based on the analogy of these proteins with the
      abundant taxon-specific lens crystallins. In addition to performing a structural
      role related to ocular transparency, corneal crystallins may also contribute to
      the corneal antioxidant systems through a variety of mechanisms including the
      direct scavenging of free radicals, the production of NAD(P)H, the metabolism
      and/or detoxification of toxic compounds (i.e. reactive aldehydes), and the
      direct absorption of UV radiation. In this review, we extend the discussion of
      the antioxidant defenses of the cornea to include these highly expressed corneal
      crystallins and address their specific capacities to minimize oxidative damage.

PMID- 18077196
TI  - Analysis of the AIDA-I gene sequence and prevalence in Escherichia coli isolates
      from pigs with post-weaning diarrhoea and oedema disease.
AB  - Three hundred and twenty-four strains of Escherichia coli isolated from weaned
      pigs with diarrhoea or oedema disease in Eastern China were screened by multiplex
      PCR for the presence of the gene encoding adhesin involved in diffuse adhesion I
      (AIDA-I). Two AIDA-I positive strains were subjected to analysis of the
      nucleotide sequence of the complete orfA and orfB of the AIDA gene. The AIDA-I
      positive E. coli isolates were also assessed for five fimbriae (F4, F5, F6, F18
      and F41) by monoclonal antibodies and for toxin genes (STa, STb, LT, EAST1,
      Stx2e) by PCR. Twenty-one (6.5%) of the isolates possessed AIDA-I genes. Of these
      isolates, two carried AIDA-I genes as the only demonstrated virulence factors,
      and the remaining isolates carried other virulence factor genes. Comparing the
      AIDA-I sequence from porcine and human sources, a high homology of orfA both in
      porcine E. coli and human E. coli was observed. However, each orfB of the two
      porcine E. coli isolates was 3864 nucleotides long compared with 3861 for the E.
      coli 2787 orfB, and showed 96.5% homology to E. coli 2787. The data indicated (1)
      that AIDA-I may be an occasional virulence factor in post-weaning diarrhoea and
      oedema disease in pigs, (2) that it has the potential to transfer between porcine
      and human E. coli, and (3) that there is a genetic diversity in orfB between
      human and porcine E. coli.

PMID- 18077197
TI  - Pain, disability and coping reflected in the diurnal cortisol variability in
      patients scheduled for lumbar disc surgery.
AB  - BACKGROUND: Symptoms of lumbar disc herniation can be induced by both mechanical
      compression of the nerve roots and by biochemical irritants from the disc
      tissues. Proinflammatory cytokines, as well as stress are potent stimulators of
      the hypothalamic-pituitary-adrenal axis, reflected in enhanced release of
      cortisol from the adrenal cortex. Altered cortisol production is also associated
      to behaviour and coping patterns. The aim of the present study was to explore the
      relation between pain, physical function, psychosocial factors and quality of
      life to the diurnal cortisol variability, in patients with lumbar disc
      herniation. METHOD: This study had a cross-sectional design. Forty-two patients
      with lumbar disc herniation, verified by magnetic resonance imaging and a
      clinical examination by an orthopaedic surgeon, were included in the study. All
      patients were scheduled for disc surgery. The diurnal cortisol variability was
      examined before surgery. The patients were dichotomised into two groups based on
      low or high diurnal cortisol variability. Pain, disability, work related stress,
      quality of life, coping and fear avoidance beliefs, were estimated by
      standardised questionnaires. RESULTS: The low diurnal cortisol variability group
      was distinguished by a higher median score regarding leg pain at activity and
      significantly more disability (p<0.05). The patients with a low diurnal cortisol
      variability had significantly lower coping self-statement scores, but higher pain
      coping catastrophising scores (p<0.05). CONCLUSION: Patients with lumbar disc
      herniation and a low diurnal cortisol variability had lower physical function,
      perceived lower possibilities of influencing their pain, and were more prone to
      catastrophise than patients with lumbar disc herniation and a high diurnal
      cortisol variability.

PMID- 18077198
TI  - Characterization of L-aminocarnitine, an inhibitor of fatty acid oxidation.
AB  - The pathogenesis of hypoketotic hypoglycemia and cardiomyopathy in patients with
      fatty acid oxidation (FAO) disorders is still poorly understood. In vitro studies
      are hampered by the lack of natural mutants to asses the effect of FAO
      inhibition. In addition, only a few inhibitors of FAO are known. Furthermore,
      most inhibitors of FAO are activating ligands of peroxisome proliferator
      activated receptors (PPARs). We show that l-aminocarnitine (L-AC), a carnitine
      analog, inhibits FAO efficiently, but does not activate PPAR. L-AC inhibits
      carnitine palmitoyltransferase (CPT) with different sensitivities towards CPT1
      and CPT2, as well as carnitine acylcarnitine translocase (CACT). We further
      characterized L-AC using fibroblasts cell lines from controls and patients with
      different FAO defects. In these cell lines acylcarnitine profiles were determined
      in culture medium after loading with [U-(13)C]palmitic acid. In control
      fibroblasts, L-AC inhibits FAO leading to a reduction of C2-acylcarnitine and
      elevation of C16-acylcarnitine. In very long-chain acyl-CoA dehydrogenase (VLCAD)
      deficient fibroblasts, L-AC decreased the elevated C14-acylcarnitine and
      increased C16-acylcarnitine. In CACT and CPT2-deficient cell lines, L-AC did not
      change the already elevated C16-acylcarnitine level, showing that CPT1 is not
      inhibited. Oxidation of pristanic acid was only partly inhibited at high L-AC
      concentrations, indicating minimal CACT inhibition. Therefore, we conclude that
      in intact cells L-AC inhibits CPT2. Combined with our observation that l-AC does
      not activate PPAR, we suggest that L-AC is useful to simulate a FAO defect in
      cells from different origin.

PMID- 18077199
TI  - Clinical course of pyruvate kinase deficiency in Abyssinian and Somali cats.
AB  - The objective of this study was to examine clinical signs, laboratory parameters,
      and course of disease in Abyssinian and Somali cats with pyruvate kinase (PK)
      deficiency. The clinical course of 25 PK-deficient cats was followed over a time
      period of 0.8-11.3 years (median 4.3). Eleven cats (age 0.8-7.8 years, median
      4.4) did not show signs according to the owners. In 14 cats (age 0.1-5 years,
      median 1.7) the owners noted lethargy (10), diarrhoea (seven), pale mucous
      membranes (six), inappetence (six), poor coat quality (six), weight loss (four),
      icterus (four), and pica (two). Sixteen cats had been used for breeding at least
      once before diagnosis. Laboratory abnormalities included anaemia (70%), increased
      aggregated reticulocyte counts (94%), hyperglobulinaemia (80%),
      hyperbilirubinaemia (53%), and increased liver enzymes (47%). Six of 25 affected
      cats died (four) or were euthanased (two) at ages ranging from 1.3 to 11.3 years
      (median 4.1) presumably because of PK-deficiency. These findings emphasise that
      PK deficiency shows variation in age of onset and severity of signs. As PK
      deficient cats can be asymptomatic testing for PK deficiency before breeding is
      strongly recommended.

PMID- 18077200
TI  - Long chain polyunsaturated fatty acids alter membrane-bound RANK-L expression and
      osteoprotegerin secretion by MC3T3-E1 osteoblast-like cells.
AB  - Inflammation triggers an increase in osteoclast (bone resorbing cell) number and
      activity. Osteoclastogenesis is largely controlled by a triad of proteins
      consisting of a receptor (RANK), a ligand (RANK-L) and a decoy receptor
      (osteoprotegerin, OPG). Whilst RANK is expressed by osteoclasts, RANK-L and OPG
      are expressed by osteoblasts. The long chain polyunsaturated fatty acid (LCPUFA)
      arachidonic acid (AA, 20:4n-6) and its metabolite prostaglandin E2 (PGE2), are
      pro-inflammatory and PGE2 is a potent stimulator of RANKL expression. Various
      LCPUFAs such as eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA,
      22:6n-3) and gamma-linolenic acid (GLA, 18:3n-6) have anti-inflammatory activity.
      We aimed to determine if AA itself can stimulate RANKL expression and whether
      EPA, DHA and GLA inhibit RANKL expression in osteoblasts. MC3T3-E1/4 osteoblast
      like cells were cultured under standard conditions with each of the LCPUFAs
      (5microg/ml) for 48h. Membrane-bound RANKL expression was measured by flow
      cytometry and OPG secretion measured by ELISA. In a second experiment, RANKL
      expression in MC3T3-E1/4 cells was stimulated by PGE2 treatment and the effect of
      EPA, DHA and GLA on membrane-bound RANKL expression and OPG secretion determined.
      The percentage of RANKL-positive cells was higher (p<0.05) than controls
      following treatment with AA or GLA but not after co-treatment with the
      cyclooxygenase inhibitor, indomethacin. DHA and EPA had no effect on membrane
      bound RANKL expression under standard cell culture conditions. Secretion of OPG
      was lower (p<0.05) in AA-treated cells but not significantly different from
      controls in GLA, EPA or DHA treated cells. Treatment with prostaglandin E2 (PGE2)
      resulted in an increase (p<0.05) in the percentage of RANK-L positive cells and a
      decrease (p<0.05) in mean OPG secretion. The percentage of RANKL positive cells
      was significantly lower following co-treatment with PGE2 and either DHA or EPA
      compared to treatment with PGE2 alone. Mean OPG secretion remained lower than
      controls in cells treated with PGE2 regardless of co-treatment with EPA or DHA.
      Results from this study suggest COX products of GLA and AA induce membrane-bound
      RANKL expression in MC3T3-E1/4 cells. EPA and DHA have no effect on membrane
      bound RANKL expression in cells cultured under standard conditions however both
      EPA and DHA inhibit the PGE2-induced increase in RANKL expression in MC3T3-E1/4
      cells.

PMID- 18077201
TI  - Prospective study on procalcitonin and other systemic infection markers in
      patients with leukocytosis.
AB  - OBJECTIVE: To better assess the diagnosis of an infection in patients presenting
      at an emergency department with peripheral blood leukocytosis (>10 x 10(9)
      cells/l) on laboratory testing. METHODS: We prospectively evaluated serum
      procalcitonin concentration (PCT), C-reactive protein (CRP), and erythrocyte
      sedimentation rate (ESR). Patients were divided into two groups according to
      their final diagnosis: patients with infection and those without infection. PCT,
      CRP, and ESR were compared between these groups. Sensitivity, specificity,
      positive predictive values, negative predictive values, receiver operating
      characteristic curves, and areas under the curves were calculated for each
      biological measurement. RESULTS: Out of 173 patients, 99 (57%) had a final
      diagnosis of systemic infection. If a cutoff point of 0.5 ng/ml is considered,
      procalcitonin concentration had a sensitivity of 0.57, a specificity of 0.85, a
      negative predictive value of 0.59, and a positive predictive value of 0.84 for
      the diagnosis of a systemic infection. Adding CRP or ESR to PCT gave no more
      information (p=0.84). CONCLUSIONS: Only about half of the patients attending the
      emergency department with leukocytosis were suffering from an infection.
      Determination of the procalcitonin level may be useful for these patients,
      particularly in the case of a value higher than 0.5 ng/ml.

PMID- 18077202
TI  - A parametrical study of disinfection with hydrodynamic cavitation.
AB  - The physical and chemical conditions generated by cavitation bubbles can be used
      to destroy microorganisms and disinfect wastewater. The effect of different
      cavitation chamber designs and diverse operational parameters on the inactivation
      rate of Escherichia coli have been studied and used to understand the mechanisms
      involved in cell disruption.

PMID- 18077203
TI  - Protease-activated receptor-2 (PAR-2) is a weak enhancer of mucin secretion by
      human bronchial epithelial cells in vitro.
AB  - PAR-2, a member of a family of G-protein-coupled receptors, can be activated by
      serine proteases via proteolytic cleavage. PAR-2 expression is known to be
      upregulated in respiratory epithelium subsequent to inflammation in asthma and
      chronic obstructive pulmonary disease (COPD). Since these diseases also are
      characterized by excessive mucus production and secretion, we investigated
      whether PAR-2 could be linked to mucin hypersecretion by airway epithelium.
      Normal human bronchial epithelial (NHBE) cells in primary culture or the human
      bronchial epithelial cell lines, NCI-H292 and HBE-1, were used. NHBE, NCI-H292,
      and HBE-1 cells expressed prominent levels of PAR-2 protein. Short-term (30min)
      exposure of cells to the synthetic PAR-2 agonist peptide (SLIGKV-NH2) elicited a
      small but statistically significant increase in mucin secretion at high
      concentrations (100microM and 1000microM), compared to a control peptide with
      reversed amino acid sequence (VKGILS-NH2). Neither human lung tryptase nor bovine
      pancreatic trypsin, both PAR-2 agonists, affected NHBE cell mucin secretion when
      added over a range of concentrations. Knockdown of PAR-2 expression by siRNA
      blocked the stimulatory effect of the AP. The results suggest that, since PAR-2
      activation only weakly increases mucin secretion by human airway epithelial cells
      in vitro, PAR-2 probably is not a significant contributor to mucin hypersecretion
      in inflamed airways.

PMID- 18077204
TI  - Understanding gibberellic acid signaling--are we there yet?
AB  - The phytohormone gibberellic acid (GA) controls important aspects of plant growth
      such as seed germination, elongation growth, and flowering. The key components of
      the GA signaling pathway have been identified over the past 10 years. The current
      view is that GA binds to a soluble GID1 receptor, which interacts with the DELLA
      repressor proteins in a GA-dependent manner and thereby induces DELLA protein
      degradation via the E3 ubiquitin ligase SCF(GID2/SLY1). GA-dependent growth
      responses can generally be correlated with and be explained by changes in DELLA
      repressor abundance, where the DELLA repressor exerts a growth restraint that is
      relieved upon its degradation. However, it is obvious that other mechanisms must
      exist that control the activity of this pathway. This review discusses recent
      advances in the understanding of GA signaling, of its homeostasis, and of its
      cross-talk with other signaling pathways.

PMID- 18077205
TI  - Saccharinato complexes of Ce(V) with 2-hydroxypyridine: synthesis, spectroscopic
      and thermal characteristics of [Ce(sac)2(SO4)(H2O)4] and [Ce(sac)2(SO4)(PyOH)2].
AB  - The synthesis of Ce(IV) complexes [Ce(sac)2(SO4)(H2O)4] (1) and [Ce(sac)2
      (SO4)(PyOH)2] (2) (sac=saccharinate, PyOH=2-hydroxypyridine) starting with sodium
      saccharinate is described. Their vibrational and nuclear magnetic resonance (1H,
      13C) spectra as well as their thermal mode of degradation were investigated. The
      data indicate that sac in complex 1 behaves as a monodentate ligand through the
      nitrogen atoms. Saccharinato ligand in complex 2 shows different mode of
      coordination, where it behaves as tridentate and binds Ce(IV) through its
      carbonylic oxygen, nitrogen and sulphonylic oxygen atoms. The most probable
      structure in complex 2 is that, units of [Ce(sac)2(SO4)(PyOH)2] are linked by
      bridges of the O- of sac sulphonyl leading to polymeric chains.

PMID- 18077206
TI  - On the dipole moments and first-order hyperpolarizability of N,N-bis(4
      bromobutyl)-4-nitrobenzenamine.
AB  - The nonlinear optical molecule N,N-bis(4-bromobutyl)-4-nitrobenzenamine was
      synthesized. The ground state dipole moment was determined by the Debye
      Guggenheim method. A solvent mixture of acetonitrile and toluene was used for the
      solvatochromic determination of the excited state dipole moment. Excited state
      has a high value for the dipole moment which indicated a higher degree of charge
      transfer from the donor to the acceptor moiety on excitation by light. The first
      hyperpolarizability (beta(ijk)) of the molecule was evaluated assuming the two
      level model of the first hyperpolarizability.

PMID- 18077207
TI  - EEG spectral power and sleepiness during 24 h of sustained wakefulness in
      patients with obstructive sleep apnea syndrome.
AB  - OBJECTIVE: This study investigated if obstructive sleep apnea syndrome (OSAS) may
      be associated with higher activity in different frequency bands of the EEG during
      a sustained wakefulness paradigm. METHODS: Twelve OSA patients and 8 healthy
      controls were studied with the Karolinska Drowsiness Test (KDT) and subjective
      ratings of sleepiness (VAS and KSS) conducted every hour during 24 h of sustained
      wakefulness. RESULTS: The waking EEG activity, mainly in the low (0.5-7.8 Hz) and
      fast (12.7-29.2 Hz) frequency band, increased as time awake progressed in both
      groups but more obviously in OSA patients. A similar pattern was observed for
      rated sleepiness in both groups. Moreover, VAS ratings of alertness were closely
      related to the awake theta, fast alpha and beta bands in controls but not in OSA
      patients. CONCLUSIONS: OSAS was associated with a wake-dependent increase in low
      (0.5-7.8 Hz) and fast (12.7-29.2 Hz) frequency range activity. Variations in
      behavioural sleepiness measured by VAS ratings closely reflect most of the waking
      EEG parameters in controls but not in OSA patients. SIGNIFICANCE: In a sustained
      wakefulness paradigm, higher activity in delta, theta and beta bands associated
      with OSAS indicates that OSA patients show marked signs of higher sleepiness and
      stronger efforts than controls to stay awake, even though they tend to
      underestimate their sleepiness.

PMID- 18077208
TI  - Towards an independent brain-computer interface using steady state visual evoked
      potentials.
AB  - OBJECTIVE: Brain-computer interface (BCI) systems using steady state visual
      evoked potentials (SSVEPs) have allowed healthy subjects to communicate. However,
      these systems may not work in severely disabled users because they may depend on
      gaze shifting. This study evaluates the hypothesis that overlapping stimuli can
      evoke changes in SSVEP activity sufficient to control a BCI. This would provide
      evidence that SSVEP BCIs could be used without shifting gaze. METHODS: Subjects
      viewed a display containing two images that each oscillated at a different
      frequency. Different conditions used overlapping or non-overlapping images to
      explore dependence on gaze function. Subjects were asked to direct attention to
      one or the other of these images during each of 12 one-minute runs. RESULTS: Half
      of the subjects produced differences in SSVEP activity elicited by overlapping
      stimuli that could support BCI control. In all remaining users, differences did
      exist at corresponding frequencies but were not strong enough to allow effective
      control. CONCLUSIONS: The data demonstrate that SSVEP differences sufficient for
      BCI control may be elicited by selective attention to one of two overlapping
      stimuli. Thus, some SSVEP-based BCI approaches may not depend on gaze control.
      The nature and extent of any BCI's dependence on muscle activity is a function of
      many factors, including the display, task, environment, and user. SIGNIFICANCE:
      SSVEP BCIs might function in severely disabled users unable to reliably control
      gaze. Further research with these users is necessary to explore the optimal
      parameters of such a system and validate online performance in a home
      environment.

PMID- 18077209
TI  - Low-dose erythropoietin improves cardiac function in experimental heart failure
      without increasing haematocrit.
AB  - BACKGROUND: Erythropoietin (EPO) may improve cardiac function and induce
      neovascularisation in experimental models of chronic heart failure (CHF).
      However, the increased haematocrit associated with EPO treatment might exert
      concomitant deleterious effects. AIM: To investigate the haematocrit independent
      effects of EPO on cardiac function. METHODS AND RESULTS: Rats underwent permanent
      coronary artery ligation to induce myocardial infarction (MI) or sham surgery.
      Three weeks after MI, rats were randomly allocated to treatment with vehicle (MI)
      or the long-acting EPO analogue darbepoetin alfa administered in a high (40
      microg/kg/3 weeks, MI-EPO-high) or a low-dose (0.4 microg/kg/3 weeks, MI-EPO
      low). After 9 weeks, haemodynamic parameters, myocardial histology and Myosin
      Heavy Chain (MHC) isoforms were determined. High-dose EPO resulted in a
      significant increase in haematocrit (p<0.01) while low-dose EPO had no effect on
      haematocrit levels. EPO significantly improved cardiac function in both EPO
      groups, reflected by increased left ventricular (LV)-developed pressure and
      improved contractility (dP/dt(max)) and relaxation (dP/dt(min)) indices of the LV
      at 9-weeks (all p<0.05 compared to MI). The improved cardiac function was
      associated with increased capillary growth (38% in MI-EPO-high (p<0.01) and 27%
      in MI-EPO-low (p<0.05)) and an attenuated switch to slow beta-MHC isoforms in
      both EPO groups. CONCLUSIONS: EPO improves cardiac function and induces
      neovascularisation at a dose that does not increase haematocrit, thereby
      circumventing the possible deleterious effects of increased erythropoiesis.

PMID- 18077210
TI  - Ultrasound lung comets for the differential diagnosis of acute cardiogenic
      dyspnoea: a comparison with natriuretic peptides.
AB  - BACKGROUND: Acute dyspnoea as a presenting symptom is a frequent diagnostic
      challenge for physicians. The main differential diagnosis is between dyspnoea of
      cardiac and non-cardiac origin. Natriuretic peptides have been shown to be useful
      in this setting. Ultrasound lung comets (ULCs) are a simple, echographic method
      which can be used to assess pulmonary congestion. AIM: To evaluate the accuracy
      of ULCs for predicting dyspnoea of cardiac origin compared to natriuretic
      peptides. METHODS: We evaluated 149 patients admitted with acute dyspnoea. Chest
      sonography and NT-proBNP assessments were performed a maximum of 4 h apart and
      independently analyzed. ULCs were evaluated via cardiac probes placed on the
      anterior and lateral chest. Two independent physicians, blinded to ULCs and NT
      proBNP findings, reviewed all the medical records to establish the aetiologic
      diagnosis of dyspnoea. RESULTS: Cardiogenic dyspnoea was confirmed in 122
      patients and ruled-out in 27 patients. The number of ULCs was significantly
      correlated to NT-proBNP values (r=.69, p<.0001). Receiver operating
      characteristic analysis, showed an area under the curve of .893 for ULCs and .978
      (p=.001) for NT-proBNP, in predicting the cardiac origin of dyspnoea.
      CONCLUSIONS: In patients admitted with acute dyspnoea, pulmonary congestion,
      sonographically imaged as ULCs, is significantly correlated to NT-proBNP values.
      The accuracy of ULCs in predicting the cardiac origin of dyspnoea is high.

PMID- 18077211
TI  - Nasal continuous positive airway pressure treatment reduces systemic oxidative
      stress in patients with severe obstructive sleep apnea syndrome.
AB  - OBJECTIVE: To evaluate whether nasal continuous positive airway pressure (nCPAP)
      reduces oxidative stress in patients with severe obstructive sleep apnea (OSA)
      syndrome. MATERIALS AND METHODS: Forty-six patients with severe OSA (AHI> or =30)
      requiring nasal CPAP treatment and 46 controls (subjects without OSA and with
      mild OSA as defined by an AHI<15) were enrolled. Oxidative stress was evaluated
      in blood samples with a commercially available automated spectrophotometric assay
      (D-ROMs test, Diacron, Grosseto, Italy). Blood samples were collected the evening
      before (10:00 p.m.) and the morning after (07:00 a.m.) a diagnostic
      polysomnography. Patients with severe OSA syndrome were subsequently submitted to
      a second polysomnography with nasal CPAP titration the following night. Using the
      same schedule we collected blood samples from the patients the morning after the
      nCPAP titration and after two months of nCPAP treatment. RESULTS: Patients with
      severe OSA presented higher levels of oxidative stress than patients with AHI<15
      in the evening and in the morning (357.57+/-13.07 UCarr vs. 319.28+/-12.66 UCarr,
      p=0.038, and 371.83+/-12.83 UCarr vs. 328.09+/-11.76 UCarr, p=0.014,
      respectively). Patients with severe OSA presented a significant reduction the
      levels of oxidative stress the morning after the nCPAP titration study (371.83+/
      12.83 UCarr vs. 298.21+/-9.62 UCarr, p=0.001) and this reduction was further
      preserved after a period of two months of nCPAP treatment (293.72+/-6.55 UCarr,
      p=0.001 vs. baseline). Statistically significant correlations were observed
      between levels of oxidative stress and nocturnal polysomnography (NPSG) markers
      as oxygen desaturation index (ODI), arousal index (AI), lowest oxygen saturation
      of hemoglobin, and mean oxygen saturation of hemoglobin. CONCLUSIONS: Patients
      with severe OSA syndrome presented increased systemic oxidative stress. A single
      night of nCPAP treatment significantly reduced the levels of oxidative stress in
      patients with severe OSA syndrome, and this reduction was maintained at least
      after two months of nCPAP treatment.

PMID- 18077212
TI  - A "polypill" for acute tendon pain in athletes with tendinopathy?
AB  - Acute tendon pain in athletes is a condition that is difficult to manage. There
      are few treatment options that give adequate pain relief and have a theoretical
      basis for efficacy. We report the use of a novel "polypill" for tendon pain, and
      provide evidence for the basis for its use. We present it to stimulate discussion
      and research into a new area of tendinopathy.

PMID- 18077213
TI  - Relationship between brief and prolonged repeated sprint ability.
AB  - Repeated sprint ability (RSA) is often assessed over a brief time period with
      limited recovery between sprints; however, it is not known how performance in
      such tests is related to the ability to perform repeated sprints over a more
      prolonged duration. Eighteen boys aged 15.3+/-0.5 years completed both a brief
      and prolonged RSA test on a non-motorised treadmill. The brief RSA test consisted
      of seven 5s sprints with 20s of recovery between sprints and the prolonged RSA
      test lasted for 42min and included a 5s sprint every 2min. There was a moderate
      but significant relationship between the mean speed in both tests (r=0.51,
      p<0.05). The maximal speed achieved in a single sprint provided strong
      relationships with both brief RSA speed (r> or =0.72, p<0.001) and prolonged RSA
      speed (r> or =0.77, p<0.001). Total work done during the brief protocol was
      significantly correlated to both total work (r=0.81, p<0.001) and total sprint
      distance (r=0.79, p<0.001) during the prolonged test. There were no significant
      relationships between percentage decrement scores across the two protocols (r< or
      =0.33, p>0.05). Maximal speed in a single sprint and total work done during
      repeated sprints represent general qualities related to RSA that are independent
      of the test protocol. The mean speed and decrements in performance represent
      specific RSA qualities, which are dependent on the frequency of sprints and
      duration of the test protocol.

PMID- 18077214
TI  - Effect of the HamSprint Drills training programme on lower limb neuromuscular
      control in Australian football players.
AB  - This study examined the effect of the HamSprint Drills training programme and
      conventional football practice warm-up on lower limb neuromuscular control. The
      purpose-built active movement extent discrimination apparatus was used to assess
      lower limb neuromuscular control in 29 footballers from one professional
      Australian Football League club. Without vision of the contact point,
      participants performed 40 backward swing movement trials with each leg and made a
      judgment of the magnitude of each movement. Scores representing the ability to
      discriminate between different movement extents were calculated as the area under
      the player's receiver operating characteristic curve, constructed using non
      parametric signal detection theory methods. Participants were randomized to
      either an intervention or control group that performed different procedures in
      the warm-up prior to football practice sessions over a 6-week period, and then
      were re-tested. The intervention group performed the HamSprint programme-drills
      specific to the improvement of running technique, co-ordination and hamstring
      function. The control group performed their usual warm-up of stretching, running,
      and increasingly intense football drills. Backward leg swing extent
      discrimination was significantly better in players following the 6-week HamSprint
      programme when compared to discrimination scores of players who performed their
      usual practice warm-up only. Significant improvement was observed in lower limb
      neuromuscular control in movements similar to the late-swing early stance phase
      of running. The HamSprint programme can therefore improve control in a specific
      aspect of sensorimotor system performance, and this may be useful particularly in
      athletes who have lower function levels or those deemed at risk of hamstring
      injury.

PMID- 18077215
TI  - Do differences in muscle recruitment between novice and elite cyclists reflect
      different movement patterns or less skilled muscle recruitment?
AB  - It has been shown that novice and elite cyclists use different patterns of leg
      muscle recruitment when cycling. These differences may reflect less skilled
      muscle recruitment by novice cyclists or different, but not necessarily less
      skilled, movement patterns. We compared kinematics of the pelvis and lower limbs
      and leg muscle activity during cycling between novice and elite cyclists, to
      determine if differences in leg muscle activity are associated with differences
      in movement patterns. Three-dimensional pelvic and lower limb kinematics and
      electromyographic (EMG) activity of leg muscles were measured during cycling at
      55-60, 75-80, 90-95rpm and preferred cadence. Differences were found between
      novice and elite cyclists in the recruitment of leg muscles, which were
      consistent with previous findings. Joint-angle and velocity were not different
      between groups. Absolute range of sagittal plane motion of the ankle was less in
      novice cyclists than in elite cyclists. Cadence did not influence kinematics.
      Coordination of sagittal plane motion of the hip and ankle, and knee and ankle,
      was stronger in elite cyclists. Furthermore, coordination of these movements was
      more consistent between pedal strokes in elite cyclists. Individual variance of
      kinematics was not different between groups. We conclude that differences in leg
      muscle recruitment between novice and elite cyclists may be explained in part by
      small kinematic variations at the ankle, i.e. less absolute range of motion, but
      contend that differences in muscle recruitment are primarily a reflection of more
      skilled muscle recruitment by elite cyclists.

PMID- 18077216
TI  - Physiological demands of water polo goalkeeping.
AB  - The purpose of this study was to investigate the physiological demands of water
      polo goalkeepers during competition and to examine whether the playing intensity
      of the goalkeeper decreases as the game time progresses. During eight official
      games the following measurements were performed on eight elite water polo
      goalkeepers: (1) video analysis of activities, (2) monitoring of blood lactate
      (BLa) and (3) continuous recording of heart rate (HR) responses. Mean HR of total
      mixed playing time, excluding breaks among quarters, was 134.3+/-20.3bpm for 36
      (4x9) min of game duration. The large portion of the game (85.6%) was performed
      with a HR lower than 151.4+/-2.7bpm (82.1+/-1.4% of HRpeak) an intensity
      corresponding to the players' anaerobic threshold (3.49+/-0.60mmolL(-1)).
      However, an important part of the game (14.4%) contained activities with sudden
      HR increases above the anaerobic threshold. Mean BLa accumulation at the end of
      each game period was 3.93+/-1.64mmolL(-1). Individual lactate values varied from
      2.0 to 8.3mmolL(-1). Goalkeeper exercise intensity reached its peak value
      (152.5+/-10.1bpm) whenever his team competed with one player less due to player
      exclusion. No significant differences were found in HR, BLa and the percentage of
      time spent in each of the activity categories between game periods. In
      conclusion, goalkeeper's game can be described as of intermittent nature with
      great variability in the intensity performed. The greater part of the game is
      associated with a low aerobic demand while an important part of the game contains
      activities with sudden HR increases above the anaerobic threshold implying also a
      considerable demand on anaerobic metabolism. The intensity of exercise of the
      goalkeeper does not differ from period to period.

PMID- 18077217
TI  - Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin
      alone in patients with advanced pancreatic cancer: a randomised, multicentre,
      phase II trial.
AB  - BACKGROUND: Preclinical data have suggested a synergistic effect of cetuximab
      combined with gemcitabine and cisplatin and clinical data have shown a
      substantial improvement in response and survival when gemcitabine is combined
      with a platinum analogue compared with gemcitabine alone. The aim of this study
      was to assess the activity and feasibility of a combination of cetuximab with
      gemcitabine and cisplatin compared with use of gemcitabine and cisplatin alone
      for the treatment of advanced pancreatic cancer. METHODS: In a multicentre,
      randomised phase II trial, 84 patients with advanced pancreatic cancer were
      randomly assigned to either 250 mg/m2 cetuximab weekly, after a loading dose of
      400 mg/m2, plus 1000 mg/m2 gemcitabine and 35 mg/m2 cisplatin on days 1 and 8 of
      a 21-day cycle or to the same chemotherapeutic regimen without cetuximab. The
      primary endpoint was objective response (defined as the proportion of patients
      whose best response was either partial response or complete response). Secondary
      endpoints included disease control (defined as the proportion of patients whose
      best response was either partial response, complete response, or stable disease),
      progression-free survival, and overall survival. All assessments of response at
      each site were done blindly by a local experienced radiologist who was not
      directly involved in the trial. Responses were measured according to an intention
      to-treat analysis. This trial is registered with the Clinical Trial registry,
      number NCT00536614. FINDINGS: 29 men and 13 women were randomly assigned to
      cetuximab plus gemcitabine and cisplatin (median age 61 years [range 38-78]) and
      22 men and 20 women were randomly assigned to gemcitabine and cisplatin (median
      age 64 years [range 40-76]). Seven of 40 (17.5%) patients had an objective
      response in the cetuximab group (95% CI 7.3-32.8) and five of 41 (12.2%) patients
      had an objective response in the non-cetuximab group (95% CI 4.1-26.2). No
      significant difference was noted between the groups both for objective response
      (5.3% higher in the cetuximab group [95% CI -16.5 to 27.1]; chi2 test=0.360;
      p=0.549) or for disease control (3.5% higher in the non-cetuximab group [-34.0%
      to 27.0%]; 0.446; p=0.504). Overall median follow-up was 11.8 months (range 2.5
      18.5). No significant differences between the groups were noted in median
      progression-free survival (hazard ratio 0.96, 95% CI 0.60-1.52, p=0.847) or in
      median overall survival (0.91, 0.54-1.55, p=0.739): median progression-free
      survival was 3.4 months (95% CI 2.4-5.1) in the cetuximab group and 4.2 months
      (2.6-5.4) in the non-cetuximab group; median overall survival was 7.5 months (5.1
      8.8) and 7.8 months (5.3-15.0), respectively. 33 patients from both groups had at
      least one grade 3-4 toxic effect. INTERPRETATION: The addition of cetuximab to a
      combination of gemcitabine and cisplatin does not increase response or survival
      for patients with advanced pancreatic cancer. Although toxic effects were not
      increased by cetuximab, this combination should not be further assessed in phase
      III trials.

PMID- 18077218
TI  - Retention of upper limb function in stroke survivors who have received constraint
      induced movement therapy: the EXCITE randomised trial.
AB  - BACKGROUND: The aim of constraint-induced movement therapy (CIMT) is to promote
      use of a limb that is functionally impaired after a stroke. In one form of CIMT
      to treat upper limb impairment, use of the less severely affected arm is
      restricted for many hours each weekday over 2 consecutive weeks. The EXCITE trial
      has previously shown the efficacy of this intervention for patients 3-9 months
      poststroke who were followed-up for the next 12 months. We assessed the retention
      of improvements 24 months after the intervention. METHODS: In the EXCITE trial,
      106 of 222 participants who had mild to moderate poststroke impairments were
      randomly assigned to receive CIMT rather than usual and customary care. We
      assessed this group of patients every 4 months for the primary outcome measure of
      impaired upper limb function, as measured with the Wolf motor function test
      (WMFT) and the motor activity log (MAL). Health-related quality of life, measured
      with the stroke impact scale (SIS), was a secondary outcome measure. Analysis was
      per protocol. This trial is registered with ClinicalTrials.gov, number
      NCT00057018. FINDINGS: The effects at 24 months after treatment did not decline
      from those at 12 months for time taken to complete the WMFT (-0.32 s, 95% CI 
      3.70 to 3.06), for weight lifted in the WMFT (-1.39 kg, -2.74 to -0.04), for WMFT
      grip strength (-4.39 kg, -6.91 to -1.86), for amount of use in the MAL (-0.17, 
      0.38 to 0.04), or for how well the limb was used in the MAL (-0.14, -0.34 to
      0.06). The additional changes were in the direction of increased therapeutic
      effect. For the strength components of the WMFT, p<0.0001. INTERPRETATION:
      Patients who have mild to moderate impairments 3-9 months poststroke have
      substantial improvement in functional use of the paretic upper limb and quality
      of life 2 years after a 2-week CIMT intervention. Thus, this intervention has
      persistent benefits.

PMID- 18077219
TI  - Development and evaluation of a questionnaire for measuring patient views of
      involvement in myocardial infarction care.
AB  - BACKGROUND: Patients' involvement in their healthcare has been associated with
      improved treatment outcomes in chronic illness. Less is known about the affects
      of patient involvement on the outcomes of acute illness, such as myocardial
      infarction. A better understanding of patients' views and behaviour during
      hospitalization might improve clinical practice and enhance patient involvement.
      AIM: The aim of this study was to develop and evaluate a questionnaire for
      measuring patients' perceptions of their involvement during hospitalization for
      myocardial infarction care. METHODS: Focus groups with myocardial infarction
      patients provided the basis for the construction of the questionnaire.
      Questionnaire validity and reliability were evaluated in a small pilot study and
      a larger cross-sectional study among myocardial infarction patients at eleven
      Swedish hospitals. RESULTS: The questionnaire demonstrated good validity and
      reliability, with six factors measuring patient views and behaviour regarding
      involvement. CONCLUSION: The questionnaire appears to be a useful tool for
      evaluating the perceptions and behaviour of patients regarding patient
      involvement in myocardial infarction care. Use of this questionnaire may provide
      insight regarding areas of patient-staff interaction that need improvement.
      Pinpointing such areas may lead to improved patient involvement, satisfaction
      with care, and treatment outcomes.

PMID- 18077221
TI  - Dynamic gene expression of Lin-28 during embryonic development in mouse and
      chicken.
AB  - The Caenorhabditis elegans heterochronic gene lin-28 regulates developmental
      timing in the nematode trunk. We report the dynamic expression patterns of Lin-28
      homologues in mouse and chick embryos. Whole mount in situ hybridization revealed
      specific and intriguing expression patterns of Lin-28 in the developing mouse and
      chick limb bud. Mouse Lin-28 expression was detected in both the forelimb and
      hindlimb at E9.5, but disappeared from the forelimb at E10.5, and finally from
      the forelimb and hindlimb at E11.5. Chicken Lin-28, which was first detected in
      the limb primordium at stage 15/16, was also downregulated as the stage
      proceeded. The amino acid sequences of mouse and chicken Lin-28 genes are highly
      conserved and the similar expression patterns of Lin-28 during limb development
      in mouse and chicken suggest that this heterochronic gene is also conserved
      during vertebrate limb development.

PMID- 18077220
TI  - A novel subset of memory B cells is enriched in autoreactivity and correlates
      with adverse outcomes in SLE.
AB  - We previously reported that some systemic lupus erythematosus (SLE) patients have
      a population of circulating memory B cells with >2-fold higher levels of CD19. We
      show here that the presence of CD19(hi) B cells correlates with long-term adverse
      outcomes. These B cells do not appear anergic, as they exhibit high basal levels
      of phosphorylated Syk and ERK1/2, signal transduce in response to BCR
      crosslinking, and can become plasma cells (PCs) in vitro. Autoreactive anti-Smith
      (Sm) B cells are enriched in this population and the degree of enrichment
      correlates with the log of the serum anti-Sm titer, arguing that they undergo
      clonal expansion before PC differentiation. PC differentiation may occur at sites
      of inflammation, as CD19(hi) B cells have elevated CXCR3 levels and chemotax in
      response to its ligand CXCL9. Thus, CD19(hi) B cells are precursors to anti-self
      PCs, and identify an SLE patient subset likely to experience poor clinical
      outcomes.

PMID- 18077222
TI  - The population structure of the Cryptosporidium parvum population in Scotland: a
      complex picture.
AB  - We genotyped 297 Scottish C. parvum samples using micro- and minisatellites.
      Treated as a single population, the population structure was epidemic. When
      regional populations were analysed, there was evidence of sub-population
      structure variations. This was dependent upon excluding sub-groups exhibiting
      significant genetic distance from the main population, implying genetic sub
      structuring. We tested the hypothesis that these sub-groups originated outside
      the UK and demonstrated that one sub-group clustered with Peruvian samples. A
      geographically comprehensive panel of isolates would fully confirm this result.
      These data indicate limited sub-structuring within a small geographical area, but
      substantial sub-structuring over larger geographical distances. Host movement
      influences parasite diversity and population structure, evidenced by strong
      correlation (r(2) = 0.9686) between cattle movements and parasite diversity.
      Thus, the population structure of C. parvum is complex, with sub-populations
      differing in structure and being influenced by host movements, including the
      introduction of novel multilocus genotypes from geographically distinct regions.

PMID- 18077223
TI  - Hot topics in DNA repair: the molecular basis for different disease states caused
      by mutations in TFIIH and XPG.
AB  - Alterations in genes involved in nucleotide excision repair (NER) are associated
      with three genetic disorders, xeroderma pigmentosum (XP), Cockayne syndrome (CS)
      and trichothiodystrophy (TTD). The transcription and repair factor TFIIH is a
      central component of NER and mutations of its subunits are associated with all
      three diseases. A recent report provides a molecular basis for how mutations in
      the NER endonuclease XPG that affect the interaction of TFIIH might give rise to
      CS features. In cells of XP-G patients with a combined XP and CS phenotype, XPG
      fails to associate with TFIIH and as a consequence the CAK subunit dissociates
      from core TFIIH. A simplified, but general model of how various assembly and
      disassembly states of TFIIH can be invoked to explain different disease states is
      discussed. Accordingly, defects in specific enzymatic functions typically result
      in XP, dissociation of the CAK subunit from TFIIH is associated with XP/CS and a
      more generalized destabilization of TFIIH gives rise to TTD. While this
      classification provides a useful framework to understand how alterations in TFIIH
      correlate with disease states, it does not universally apply and relevant
      exception and alternative explanations are discussed.

PMID- 18077224
TI  - APLF (C2orf13) facilitates nonhomologous end-joining and undergoes ATM-dependent
      hyperphosphorylation following ionizing radiation.
AB  - Nonhomologous end-joining (NHEJ) is the major mammalian DNA double-strand break
      (DSB) repair pathway of DSBs induced by DNA damaging agents. NHEJ is initiated by
      the recognition of DSBs by the DNA end-binding heterodimer, Ku, and the final
      step of DNA end-joining is accomplished by the XRCC4-DNA ligase IV complex. We
      demonstrate that Aprataxin and PNK-like factor (APLF), an endo/exonuclease with
      an FHA domain and unique zinc fingers (ZFs), interacts with both Ku and XRCC4-DNA
      ligase IV in human cells. The interaction of APLF with XRCC4-DNA ligase IV is FHA
      and phospho-dependent, and is mediated by CK2 phosphorylation of XRCC4 in vitro.
      In contrast, APLF associates with Ku independently of the FHA and ZF domains, and
      APLF complexes with Ku at DNA ends. APLF undergoes ionizing radiation (IR)
      induced ATM-dependent hyperphosphorylation at serine residue 116, which is highly
      conserved across mammalian APLF homologues. We demonstrate further that depletion
      of APLF in human cells by siRNA is associated with impaired NHEJ. Collectively,
      these results suggest that APLF is an ATM target that is involved in NHEJ and
      facilitates DSB repair, likely via interactions with Ku and XRCC4-DNA ligase IV.

PMID- 18077225
TI  - Children with epilepsy: are they the same on both sides of the Atlantic, and do
      the same treatments work?

PMID- 18077227
TI  - Self-induced stretch syncope of adolescence: a video-EEG documentation.
AB  - We present the first video-EEG documentation, with ECG and EMG features, of
      stretch syncope of adolescence in a young, healthy 16-year-old boy. Stretch
      syncope of adolescence is a rarely reported, benign cause of fainting in young
      patients, which can be confused with epileptic seizures. In our patient, syncopes
      were self-induced to avoid school. Dynamic transcranial Doppler showed evidence
      of blood flow decrease in both posterior cerebral arteries mimicking effects of a
      Valsalva manoeuvre. Dynamic angiogram of the vertebral arteries was normal.
      Hypotheses concerning the physiopathology are discussed. [Published with video
      sequences].

PMID- 18077226
TI  - Treatment of pediatric epilepsy: European expert opinion, 2007.
AB  - BACKGROUND: Childhood epilepsies are a heterogeneous group of conditions that
      differ in diagnostic criteria and management and have dramatically different
      outcomes. Despite increasing data on treatment of epilepsy, research findings on
      childhood epilepsy are more limited and many clinical questions remain
      unanswered, so that clinicians must often rely on clinical judgment. In such
      clinical situations, expert opinion can be especially helpful. METHODS: A survey
      on pediatric epilepsy and seizures (33 questions and approximately 650 treatment
      options) was sent to 57 European physicians specializing in pediatric epilepsy,
      42 (74%) of whom completed it. In some questions, the experts were asked to
      recommend overall treatment approaches for specific syndromes (the order in which
      they would use certain strategies). Most of the questions asked the experts to
      rate options using a modified version of the RAND 9-point scale for medical
      appropriateness. Consensus was defined as a non-random distribution of scores by
      chi-square test, with ratings used to assign a categorical rank (first
      line/usually appropriate, second line/equivocal, and third line/usually not
      appropriate) to each option. RESULTS: Valproate was treatment of choice for
      symptomatic myoclonic and generalized tonic-clonic seizures. For initial
      monotherapy for complex partial seizures, carbamazepine and oxcarbazepine were
      treatments of choice, with valproate also first line. As initial therapy for
      infantile spasms caused by tuberous sclerosis, viagabatrin was treatment of
      choice. As initial therapy for infantile spasms that are symptomatic in etiology,
      vigabatrin was also treatment of choice, with adrenocorticotropic hormone (ACTH)
      and prednisone other first-line options. As initial therapy for Lennox-Gastaut
      syndrome, valproate was treatment of choice. For acute treatment of a prolonged
      febrile seizure or cluster of seizures, rectal diazepam was treatment of choice.
      Valproate was treatment of choice as preventive therapy for febrile seizures. For
      benign childhood epilepsy with centro-temporal spikes, valproate was treatment of
      choice. For childhood and juvenile absence epilepsy, valproate was treatment of
      choice, with lamotrigine another first-line option (ethosuximide was another
      first-line option for childhood absence epilepsy). For juvenile myoclonic
      epilepsy in adolescent males, valproate was treatment of choice, with lamotrigine
      another first-line option; for juvenile myoclonic epilepsy in adolescent females,
      lamotrigine was treatment of choice, with valproate another firstline option. As
      initial therapy for neonatal status epilepticus, intravenous (IV) phenobarbital
      was treatment of choice. As initial therapy for all types of pediatric status
      epilepticus, IV diazepam was treatment of choice. For generalized tonic-clonic
      status epilepticus, rectal diazepam and IV lorazepam were also treatments of
      choice; for complex partial status epilepticus, IV lorazepam was another first
      line option. CONCLUSION: The expert panel reached consensus on many treatment
      options. Within the limits of expert opinion and with the understanding that new
      research data may take precedence, the experts' recommendations provide helpful
      guidance in situations where the medical literature is scant or lacking. The
      information in this report should be evaluated in conjunction with evidence-based
      findings.

PMID- 18077228
TI  - Mind-stretching faints.

PMID- 18077229
TI  - Clinical evaluation of attentional processes in children with benign childhood
      epilepsy with centrotemporal spikes (BCECTS).
AB  - The aim of this study was to identify the attentional processes specifically
      affected in children with benign childhood epilepsy with centrotemporal spikes
      (BCECTS). The impact of several factors - laterality of discharges, age-at-onset
      and duration of epilepsy, and medication - on these cognitive functions was also
      studied. A group of 29 children with BCECTS was evaluated using standardized
      tests performed in routine clinical practice and specifically designed to assess
      executive and attentional functions. This group obtained mean scores
      significantly lower than normative means specifically for tasks involving
      attention control processes, i.e. cognitive flexibility and inhibitory processes.
      Neither the epilepsy-related factors that we studied nor the medication appeared
      to influence performance of these tasks. These data suggest an impact of BCECTS
      on attentional processes, the most affected being attention control processes
      that develop late.

PMID- 18077230
TI  - Are dyslexia and dyscalculia associated with Rolandic epilepsy? A short report on
      ten Italian patients.
AB  - Rolandic epilepsy (RE) is the most common childhood epilepsy syndrome with a
      good, long-term outcome. Nevertheless, some studies indicate that children with
      RE have more scholastic and neuropsychological problems than controls. The
      purpose of this study was to describe neuropsychological findings in a small
      group of Italian children with RE, focusing on dyslexia and dyscalculia. Possible
      correlations between these findings and the age-at-onset of seizures, duration of
      active epilepsy, frequency, type and localization of epileptic discharges were
      examined. Children affected by RE, aged nine to eleven years were selected from
      patients admitted to the outpatient service of our Clinic. They underwent
      cognitive evaluation, specific evaluation for dyslexia and dyscalculia, and awake
      and sleep EEG recordings. We found two patients out of the ten with dyscalculia,
      one of whom also had characteristics of dyslexia. This small study suggests that
      dyscalculia and dyslexia might be more frequent than expected in children with
      RE. No significant correlations between this finding and EEG, seizure-frequency
      or age-at-onset of epilepsy were found in our patients.

PMID- 18077231
TI  - Granular cell dispersion and bilamination: two distinct histopathological
      patterns in epileptic hippocampi?
AB  - Cytoarchitectural modifications of the dentate gyrus are among the most obvious
      abnormalities observed in the hippocampal sclerosis associated with refractory
      epilepsy. Here, we examined the morphological changes of granular cells
      (dispersion, bilamination and cell loss) in sclerotic hippocampi from nine TLE
      patients, comparing abnormal and preserved areas. A total of 2,577 granular cells
      were analyzed with respect to four different histopathological patterns: areas
      with bilamination (n = 936), areas with dispersion (n = 905), areas with neuronal
      loss (n = 279), and preserved areas (n = 457). Quantitative parameters included
      somatic perimeter (P), area (A) and form factor (ff). Although different patterns
      were often observed in the same patient, highly significant differences were
      observed (p < 0.0001) when patterns were compared to one another. Since granular
      cell dispersion and bilamination have different morphological aspects in
      sclerotic hippocampi from TLE patients, we suggest that these patterns should be
      considered separately. Future studies are needed to determine the frequency with
      which these patterns occur in the general population and whether each one can
      interfere with seizure susceptibility.

PMID- 18077233
TI  - Ipsilateral blinking seizures during left fronto-temporal ictal pattern on scalp
      EEG.
AB  - We report an infant with left eye blinking seizures accompanying a left
      (ipsilateral) fronto-temporal scalp EEG ictal pattern. The epileptogenic lesion
      was a left frontal encephalomalacia along the ventriculo-peritoneal shunt tract.
      The shunt was inserted for treatment of communicating hydrocephalus. This case
      illustrates the lateralizing value of the ictal blinking. Review of the
      literature suggests that seizures with unilateral blinking are likely to be
      produced by activation of ipsilateral trigeminal fibers innervating subdural
      intracranial structures and pial vessels in temporal and frontal lobes.
      Ipsilateral blinking could also be produced by activation of the ipsilateral
      cerebellar hemisphere.

PMID- 18077232
TI  - Bilateral symmetric tonic posturing suggesting propagation to the supplementary
      motor area in a patient with precuneate cortical dysplasia.
AB  - We report a patient manifesting seizures with bilateral symmetric tonic
      posturing, which were markedly reduced after resection of the left precuneus. A
      16-year-old man had sudden onset, complex partial seizures with bilateral
      symmetric tonic posturing since the age of eight years. Magnetic resonance fluid
      attenuated inversion-recovery imaging revealed a hyperintense lesion in left
      precuneus. In almost all focal seizures recorded during an invasive EEG
      evaluation, ictal onset was detected from the inferomesial aspect of the lesion,
      but fast paroxysmal discharges from the ipsilateral supplementary motor area
      (SMA) were observed just before the clinical onset. After surgical excision of
      the EEG onset zone, including the lesion, seizure frequency was markedly (> 95%)
      reduced. By the 20th month after surgery, there were only brief nocturnal
      seizures involving slight elevation of both shoulders and slight abduction of
      both arms, with preservation of consciousness occurring once every few days.
      Invasive EEG findings and surgical outcome suggested that the epileptic activity
      originating from the epileptogenic zone may have propagated to the
      symptomatogenic zone including mainly the ipsilateral SMA. In summary, we report
      an interesting case of bilateral symmetric tonic posturing suggesting propagation
      to the SMA. MRI and invasive EEG confirmed the epileptogenic focus as a
      precuneate cortical dysplasia lesion.[Published with video sequences].

PMID- 18077234
TI  - Gelastic seizures: not always hypothalamic hamartoma.
AB  - Gelastic seizures are often associated with hypothalamic hamartomas. However,
      focal cortical dysplasias can also cause "laughing seizures", and such cases can
      be difficult to localize with EEG. This case report presents a 29-year-old woman
      who was successfully rendered free of gelastic seizures after resection of a
      frontal cortical dysplasia, localized through MRI and SPECT imaging.[Published
      with video sequences].

PMID- 18077235
TI  - Partial agenesis of the corpus callosum in a patient with juvenile myoclonic
      epilepsy.
AB  - We describe a patient who presented at our epilepsy-monitoring unit with
      myoclonic jerks, and was diagnosed with juvenile myoclonic epilepsy (JME).
      Imaging of his brain revealed partial agenesis of the corpus callosum (ACC). We
      discuss the known genetic basis of both JME and ACC, as well as the role of the
      corpus callosum (CC) in primary generalized epilepsy. Both JME and ACC are
      associated with gene loci on chromosome 15q14. Structural brain abnormalities
      other than ACC, such as atrophy of the corpus callosum have been reported in
      patients with JME. ACC has been associated with seizures, suggesting an anti
      epileptogenic role of the corpus callosum. On the other hand, corpus callosotomy
      is used to treat refractory idiopathic generalized epilepsy, which shows that the
      corpus callosum may play an epileptogenic role. The occurrence of both these
      conditions in one patient raises the question of whether they are purely
      coincidental or if there is a common basis for both. Several issues need to be
      addressed: the mechanism of seizure generalization in the setting of partial ACC,
      the possible role of other structures in generalization, and whether the ACC
      contributes to epileptogenesis as a result of the lack of a normal CC inhibitory
      effect.

PMID- 18077236
TI  - Number and arrangement of extraocular muscles in primitive gnathostomes: evidence
      from extinct placoderm fishes.
AB  - Exceptional braincase preservation in some Devonian placoderm fishes permits
      interpretation of muscles and cranial nerves controlling eye movement. Placoderms
      are the only jawed vertebrates with anterior/posterior obliques as in the jawless
      lamprey, but with the same function as the superior/inferior obliques of other
      gnathostomes. Evidence of up to seven extraocular muscles suggests that this may
      be the primitive number for jawed vertebrates. Two muscles innervated by cranial
      nerve 6 suggest homologies with lampreys and tetrapods. If the extra muscle
      acquired by gnathostomes was the internal rectus, Devonian fossils show that it
      had a similar insertion above and behind the eyestalk in both placoderms and
      basal osteichthyans.

PMID- 18077237
TI  - Social learning of novel route preferences in adult humans.
AB  - Non-human animals can acquire novel route preferences by following knowledgeable
      individuals. Such socially learned route preferences can be stably maintained
      over multiple transmission episodes, sometimes forming long-lived traditions. In
      humans, preferences for familiar routes or heavily used worn trails over
      unfamiliar ones have been described in various contexts. However, social learning
      of route preferences has not been experimentally demonstrated in humans. Here, we
      demonstrate that social learning and tradition influence route choice. We led
      adult male and female participants into a room by one of two routes. Participants
      followed the demonstrated route choices, and later remembered and preferred this
      choice even when determinably suboptimal (i.e. longer and not preferred by
      control participants) or when the choice was indicated as arbitrary (the
      demonstrator took one route to retrieve a poster that had ostensibly fallen).
      Moreover, route preferences were stably maintained over multiple transmission
      episodes. We suggest that simple social learning processes, often neglected in
      human and primate research, can result in long-lived route preferences that may
      influence a range of additional behaviour patterns.

PMID- 18077238
TI  - Rapid facial mimicry in orangutan play.
AB  - Emotional contagion enables individuals to experience emotions of others. This
      important empathic phenomenon is closely linked to facial mimicry, where facial
      displays evoke the same facial expressions in social partners. In humans, facial
      mimicry can be voluntary or involuntary, whereby its latter mode can be processed
      as rapid as within or at 1s. Thus far, studies have not provided evidence of
      rapid involuntary facial mimicry in animals. This study assessed whether rapid
      involuntary facial mimicry is present in orangutans (Pongo pygmaeus; N=25) for
      their open-mouth faces (OMFs) during everyday dyadic play. Results clearly
      indicated that orangutans rapidly mimicked OMFs of their playmates within or at
      1s. Our study revealed the first evidence on rapid involuntary facial mimicry in
      non-human mammals. This finding suggests that fundamental building blocks of
      positive emotional contagion and empathy that link to rapid involuntary facial
      mimicry in humans have homologues in non-human primates.

PMID- 18077239
TI  - Origin of tropical American burrowing reptiles by transatlantic rafting.
AB  - Populations of terrestrial or freshwater taxa that are separated by oceans can be
      explained by either oceanic dispersal or fragmentation of a previously contiguous
      land mass. Amphisbaenians, the worm lizards (approx. 165 species), are small
      squamate reptiles that are uniquely adapted to a burrowing lifestyle and inhabit
      Africa, South America, Caribbean Islands, North America, Europe and the Middle
      East. All but a few species are limbless and they rarely leave their subterranean
      burrows. Given their peculiar habits, the distribution of amphisbaenians has been
      assumed to be primarily the result of two land-mass fragmentation events: the
      split of the supercontinent Pangaea starting 200 Myr ago, separating species on
      the northern land mass (Laurasia) from those on the southern land mass
      (Gondwana), and the split of South America from Africa 100 Myr ago. Here we show
      with molecular evidence that oceanic dispersal-on floating islands-played a more
      prominent role, and that amphisbaenians crossed the Atlantic Ocean in the Eocene
      (40 Myr ago) resulting in a tropical American radiation representing one-half of
      all known amphisbaenian species. Until now, only four or five transatlantic
      dispersal events were known in terrestrial vertebrates. Significantly, this is
      the first such dispersal event to involve a group that burrows, an unexpected
      lifestyle for an oceanic disperser.

PMID- 18077240
TI  - Landscape genetics and the spatial distribution of chronic wasting disease.
AB  - Predicting the spread of wildlife disease is critical for identifying populations
      at risk, targeting surveillance and designing proactive management programmes. We
      used a landscape genetics approach to identify landscape features that influenced
      gene flow and the distribution of chronic wasting disease (CWD) in Wisconsin
      white-tailed deer. CWD prevalence was negatively correlated with genetic
      differentiation of study area deer from deer in the area of disease origin (core
      area). Genetic differentiation was greatest, and CWD prevalence lowest, in areas
      separated from the core-area by the Wisconsin River, indicating that this river
      reduced deer gene flow and probably disease spread. Features of the landscape
      that influence host dispersal and spatial patterns of disease can be identified
      based on host spatial genetic structure. Landscape genetics may be used to
      predict high-risk populations based on their genetic connection to infected
      populations and to target disease surveillance, control and preventative
      activities.

PMID- 18077241
TI  - Integrated diversification of locomotion and feeding in labrid fishes.
AB  - An organism's performance of any ecological task involves coordination of
      multiple functional systems. Feeding performance is influenced by locomotor
      abilities which are used during search and capture of prey, as well as cranial
      mechanics, which affect prey capture and processing. But, does this integration
      of functional systems manifest itself during evolution? We asked whether the
      locomotor and feeding systems evolved in association in one of the most prominent
      and diverse reef fish radiations, the Labridae. We examined features of the
      pectoral fins that affect swimming performance and aspects of the skull that
      describe force and motion of the jaws. We applied a recent phylogeny, calculated
      independent contrasts for 60 nodes and performed principal components analyses
      separately on contrasts for fin and skull traits. The major axes of fin and skull
      diversification are highly correlated; modifications of the skull to amplify the
      speed of jaw movements are correlated with changes in the pectoral fins that
      increase swimming speed, and increases in force capacity of the skull are
      associated with changes towards fins that produce high thrust at slow speeds.
      These results indicate that the labrid radiation involved a strong connection
      between locomotion and feeding abilities.

PMID- 18077242
TI  - Boltzmann, Lotka and Volterra and spatial structural evolution: an integrated
      methodology for some dynamical systems.
AB  - It is shown that Boltzmann's methods from statistical physics can be applied to a
      much wider range of systems, and in a variety of disciplines, than has been
      commonly recognized. A similar argument can be applied to the ecological models
      of Lotka and Volterra. Furthermore, it is shown that the two methodologies can be
      applied in combination to generate the Boltzmann, Lotka and Volterra (BLV)
      models. These techniques enable both spatial interaction and spatial structural
      evolution to be modelled, and it is argued that they potentially provide a much
      richer modelling methodology than that currently used in the analysis of 'scale
      free' networks.

PMID- 18077243
TI  - A comparative study of the reported performance of ab initio protein structure
      prediction algorithms.
AB  - Protein structure prediction is one of the major challenges in bioinformatics
      today. Throughout the past five decades, many different algorithmic approaches
      have been attempted, and although progress has been made the problem remains
      unsolvable even for many small proteins. While the general objective is to
      predict the three-dimensional structure from primary sequence, our current
      knowledge and computational power are simply insufficient to solve a problem of
      such high complexity. Some prediction algorithms do, however, appear to perform
      better than others, although it is not always obvious which ones they are and it
      is perhaps even less obvious why that is. In this review, the reported
      performance results from 18 different recently published prediction algorithms
      are compared. Furthermore, the general algorithmic settings most likely
      responsible for the difference in the reported performance are identified, and
      the specific settings of each of the 18 prediction algorithms are also compared.
      The average normalized r.m.s.d. scores reported range from 11.17 to 3.48. With a
      performance measure including both r.m.s.d. scores and CPU time, the currently
      best-performing prediction algorithm is identified to be the I-TASSER algorithm.
      Two of the algorithmic settings--protein representation and fragment assembly-
      were found to have definite positive influence on the running time and the
      predicted structures, respectively. There thus appears to be a clear benefit from
      incorporating this knowledge in the design of new prediction algorithms.

PMID- 18077244
TI  - Selective activation of mechanosensitive ion channels using magnetic particles.
AB  - This study reports the preliminary development of a novel magnetic particle-based
      technique that permits the application of highly localized mechanical forces
      directly to specific regions of an ion-channel structure. We demonstrate that
      this approach can be used to directly and selectively activate a mechanosensitive
      ion channel of interest, namely TREK-1. It is shown that manipulation of
      particles targeted against the extended extracellular loop region of TREK-1 leads
      to changes in whole-cell currents consistent with changes in TREK-1 activity.
      Responses were absent when particles were coated with RGD (Arg-Gly-Asp) peptide
      or when magnetic fields were applied in the absence of magnetic particles. It is
      concluded that changes in whole-cell current are the result of direct force
      application to the extracellular loop region of TREK-1 and thus these results
      implicate this region of the channel structure in mechano-gating. It is
      hypothesized that the extended loop region of TREK-1 may act as a tension spring
      that acts to regulate sensitivity to mechanical forces, in a nature similar to
      that described for MscL. The development of a technique that permits the direct
      manipulation of mechanosensitive ion channels in real time without the need for
      pharmacological drugs has huge potential benefits not only for basic biological
      research of ion-channel gating mechanisms, but also potentially as a tool for the
      treatment of human diseases caused by ion-channel dysfunction.

PMID- 18077245
TI  - Correlating cell morphology and osteoid mineralization relative to strain profile
      for bone tissue engineering applications.
AB  - A number of bone tissue engineering strategies use porous three-dimensional
      scaffolds in combination with bioreactor regimes. The ability to understand cell
      behaviour relative to strain profile will allow for the effects of mechanical
      conditioning in bone tissue engineering to be realized and optimized. We have
      designed a model system to investigate the effects of strain profile on bone cell
      behaviour. This simplified model has been designed with a view to providing
      insight into the types of strain distribution occurring across a single pore of a
      scaffold subjected to perfusion-compression conditioning. Local strains were
      calculated at the surface of the pore model using finite-element analysis.
      Scanning electron microscopy was used in secondary electron mode to identify cell
      morphology within the pore relative to local strains, while backscattered
      electron detection in combination with X-ray microanalysis was used to identify
      calcium deposition. Morphology was altered according to the level of strain
      experienced by bone cells, where cells subjected to compressive strains (up to
      0.61%) appeared extremely rounded while those experiencing zero and tensile
      strain (up to 0.81%) were well spread. Osteoid mineralization was similarly shown
      to be dose dependent with respect to substrate strain within the pore model, with
      the highest level of calcium deposition identified in the intermediate zones of
      tension/compression.

PMID- 18077246
TI  - Growth model for arbuscular mycorrhizal fungi.
AB  - In order to quantify the contribution of arbuscular mycorrhizal (AM) fungi to
      plant phosphorus nutrition, the development and extent of the external fungal
      mycelium and its nutrient uptake capacity are of particular importance. We
      develop and analyse a model of the growth of AM fungi associated with plant
      roots, suitable for describing mechanistically the effects of the fungi on solute
      uptake by plants. The model describes the development and distribution of the
      fungal mycelium in soil in terms of the creation and death of hyphae, tip-tip and
      tip-hypha anastomosis, and the nature of the root-fungus interface. It is
      calibrated and corroborated using published experimental data for hyphal length
      densities at different distances away from root surfaces. A good agreement
      between measured and simulated values was found for three fungal species with
      different morphologies: Scutellospora calospora (Nicol. & Gerd.) Walker &
      Sanders; Glomus sp.; and Acaulospora laevis Gerdemann & Trappe associated with
      Trifolium subterraneum L. The model and findings are expected to contribute to
      the quantification of the role of AM fungi in plant mineral nutrition and the
      interpretation of different foraging strategies among fungal species.

PMID- 18077247
TI  - Design principles for phase-splitting behaviour of coupled cellular oscillators:
      clues from hamsters with 'split' circadian rhythms.
AB  - Nonlinear interactions among coupled cellular oscillators are likely to underlie
      a variety of complex rhythmic behaviours. Here we consider the case of one such
      behaviour, a doubling of rhythm frequency caused by the spontaneous splitting of
      a population of synchronized oscillators into two subgroups each oscillating in
      anti-phase (phase-splitting). An example of biological phase-splitting is the
      frequency doubling of the circadian locomotor rhythm in hamsters housed in
      constant light, in which the pacemaker in the suprachiasmatic nucleus (SCN) is
      reconfigured with its left and right halves oscillating in anti-phase. We apply
      the theory of coupled phase oscillators to show that stable phase-splitting
      requires the presence of negative coupling terms, through delayed and/or
      inhibitory interactions. We also find that the inclusion of real biological
      constraints (that the SCN contains a finite number of non-identical noisy
      oscillators) implies the existence of an underlying non-uniform network
      architecture, in which the population of oscillators must interact through at
      least two types of connections. We propose that a key design principle for the
      frequency doubling of a population of biological oscillators is inhomogeneity of
      oscillator coupling.

PMID- 18077248
TI  - The population genetics of mimetic diversity in Heliconius butterflies.
AB  - Theory predicts strong stabilizing selection on warning patterns within species
      and convergent evolution among species in Mullerian mimicry systems yet
      Heliconius butterflies exhibit extreme wing pattern diversity. One potential
      explanation for the evolution of this diversity is that genetic drift
      occasionally allows novel warning patterns to reach the frequency threshold at
      which they gain protection. This idea is controversial, however, because
      Heliconius butterflies are unlikely to experience pronounced population
      subdivision and local genetic drift. To examine the fine-scale population genetic
      structure of Heliconius butterflies we genotyped 316 individuals from eight Costa
      Rican Heliconius species with 1428 AFLP markers. Six species exhibited evidence
      of population subdivision and/or isolation by distance indicating genetic
      differentiation among populations. Across species, variation in the extent of
      local genetic drift correlated with the roles different species have played in
      generating pattern diversity: species that originally generated the diversity of
      warning patterns exhibited striking population subdivision while species that
      later radiated onto these patterns had intermediate levels of genetic diversity
      and less genetic differentiation among populations. These data reveal that
      Heliconius butterflies possess the coarse population genetic structure necessary
      for local populations to experience pronounced genetic drift which, in turn,
      could explain the origin of mimetic diversity.

PMID- 18077249
TI  - Old men running: mechanical work and elastic bounce.
AB  - It is known that muscular force is reduced in old age. We investigate what are
      the effects of this phenomenon on the mechanics of running. We hypothesized that
      the deficit in force would result in a lower push, causing reduced amplitude of
      the vertical oscillation, with smaller elastic energy storage and increased step
      frequency. To test this hypothesis, we measured the mechanical energy of the
      centre of mass of the body during running in old and young subjects. The
      amplitude of the oscillation is indeed reduced in the old subjects, resulting in
      an approximately 20% smaller elastic recovery and a greater step frequency (3.7
      versus 2.8 Hz, p=1.9x10(-5), at 15-17 km h(-1)). Interestingly, the greater step
      frequency is due to a lower aerial time, and not to a greater natural frequency
      of the system, which is similar in old and young subjects (3.6 versus 3.4 Hz,
      p=0.2). Moreover, we find that in the old subjects, the step frequency is always
      similar to the natural frequency, even at the highest speeds. This is at variance
      with young subjects who adopt a step frequency lower than the natural frequency
      at high speeds, to contain the aerobic energy expenditure. Finally, the external
      work to maintain the motion of the centre of mass is reduced in the old subjects
      (0.9 versus 1.2 J kg(-1) m(-1), p=5.1x10(-6)) due to the lower work done against
      gravity, but the higher step frequency involves a greater internal work to reset
      the limbs at each step. The net result is that the total work increases with
      speed more steeply in the old subjects than in young subjects.

PMID- 18077250
TI  - Larval competition alters susceptibility of adult Aedes mosquitoes to dengue
      infection.
AB  - Dengue, the most important human arboviral disease, is transmitted primarily by
      Aedes aegypti and, to a lesser extent, by Aedes albopictus. The current
      distributions of these invasive species overlap and are affected by interspecific
      larval competition in their container habitats. Here we report that competition
      also enhances dengue infection and dissemination rates in one of these two vector
      species. We determined the effects of competition on adult A. aegypti and A.
      albopictus, comparing their susceptibility to infection with a Southeast Asian
      strain of dengue-2 virus. High levels of intra- or interspecific competition
      among larvae enhanced the susceptibility of A. albopictus to dengue virus
      infection and potential for transmission, as indicated by disseminated
      infections. Doubling the number of competing larvae (A. albopictus or A.
      aegypti), led to a significant (more than 60%) increase in the proportion of A.
      albopictus with disseminated dengue-2 infection. Competition-enhanced vector
      competence appears to result from a reduction in 'barriers' (morphological or
      physiological) to virus infection and dissemination and may contribute to the
      importance of A. albopictus in dengue transmission. Similar results for other
      unrelated arboviruses suggest that larval competition, common in mosquitoes,
      should be considered in estimates of vector competence for pathogens that infect
      humans.

PMID- 18077251
TI  - Category learning induces position invariance of pattern recognition across the
      visual field.
AB  - Human object recognition is considered to be largely invariant to translation
      across the visual field. However, the origin of this invariance to positional
      changes has remained elusive, since numerous studies found that the ability to
      discriminate between visual patterns develops in a largely location-specific
      manner, with only a limited transfer to novel visual field positions. In order to
      reconcile these contradicting observations, we traced the acquisition of
      categories of unfamiliar grey-level patterns within an interleaved learning and
      testing paradigm that involved either the same or different retinal locations.
      Our results show that position invariance is an emergent property of category
      learning. Pattern categories acquired over several hours at a fixed location in
      either the peripheral or central visual field gradually become accessible at new
      locations without any position-specific feedback. Furthermore, categories of
      novel patterns presented in the left hemifield are distinctly faster learnt and
      better generalized to other locations than those learnt in the right hemifield.
      Our results suggest that during learning initially position-specific
      representations of categories based on spatial pattern structure become encoded
      in a relational, position-invariant format. Such representational shifts may
      provide a generic mechanism to achieve perceptual invariance in object
      recognition.

PMID- 18077252
TI  - The trade-off between number and size of offspring in humans and other primates.
AB  - Life-history theory posits a fundamental trade-off between number and size of
      offspring that structures the variability in parental investment across and
      within species. We investigate this 'quantity-quality' trade-off across primates
      and present evidence that a similar trade-off is also found across natural
      fertility human societies. Restating the classic Smith-Fretwell model in terms of
      allometric scaling of resource supply and offspring investment predicts an
      inverse scaling relation between birth rate and offspring size and a (-1/4) power
      scaling between birth rate and body size. We show that these theoretically
      predicted relationships, in particular the inverse scaling between number and
      size of offspring, tend to hold across increasingly finer scales of analyses
      (i.e. from mammals to primates to apes to humans). The advantage of this approach
      is that the quantity-quality trade-off in humans is placed into a general
      framework of parental investment that follows directly from first principles of
      energetic allocation.

PMID- 18077253
TI  - Dispersing brush mice prefer habitat like home.
AB  - During natal dispersal, young animals leave their natal area and search for a new
      area to live. In species in which individuals inhabit different types of habitat,
      experience with a natal habitat may increase the probability that a disperser
      will select the same type of habitat post-dispersal (natal habitat preference
      induction or NHPI). Despite considerable interest in the ecological and the
      evolutionary implications of NHPI, we lack empirical evidence that it occurs in
      nature. Here we show that dispersing brush mice (Peromyscus boylii) are more
      likely to search and settle within their natal habitat type than expected based
      on habitat availability. These results document the occurrence of NHPI in nature
      and highlight the relevance of experience-generated habitat preferences for
      ecological and evolutionary processes.

PMID- 18077254
TI  - Human cerebral response to animal affective vocalizations.
AB  - It is presently unknown whether our response to affective vocalizations is
      specific to those generated by humans or more universal, triggered by emotionally
      matched vocalizations generated by other species. Here, we used functional
      magnetic resonance imaging in normal participants to measure cerebral activity
      during auditory stimulation with affectively valenced animal vocalizations, some
      familiar (cats) and others not (rhesus monkeys). Positively versus negatively
      valenced vocalizations from cats and monkeys elicited different cerebral
      responses despite the participants' inability to differentiate the valence of
      these animal vocalizations by overt behavioural responses. Moreover, the
      comparison with human non-speech affective vocalizations revealed a common
      response to the valence in orbitofrontal cortex, a key component on the limbic
      system. These findings suggest that the neural mechanisms involved in processing
      human affective vocalizations may be recruited by heterospecific affective
      vocalizations at an unconscious level, supporting claims of shared emotional
      systems across species.

PMID- 18077255
TI  - Intrasexual competition among females and the stabilization of a conspicuous
      colour polymorphism in a Lake Victoria cichlid fish.
AB  - The maintenance of colour polymorphisms within populations has been a long
      standing interest in evolutionary ecology. African cichlid fish contain some of
      the most striking known cases of this phenomenon. Intrasexual selection can be
      negative frequency dependent when males bias aggression towards phenotypically
      similar rivals, stabilizing male colour polymorphisms. We propose that where
      females are territorial and competitive, aggression biases in females may also
      promote coexistence of female morphs. We studied a polymorphic population of the
      cichlid fish Neochromis omnicaeruleus from Lake Victoria, in which three distinct
      female colour morphs coexist: one plain brown and two blotched morphs. Using
      simulated intruder choice tests in the laboratory, we show that wild-caught
      females of each morph bias aggression towards females of their own morph,
      suggesting that females of all three morphs may have an advantage when their
      morph is locally the least abundant. This mechanism may contribute to the
      establishment and stabilization of colour polymorphisms. Next, by crossing the
      morphs, we generated sisters belonging to different colour morphs. We find no
      sign of aggression bias in these sisters, making pleiotropy unlikely to explain
      the association between colour and aggression bias in wild fish, which is
      maintained in the face of gene flow. We conclude that female-female aggression
      may be one important force for stabilizing colour polymorphism in cichlid fish.

PMID- 18077256
TI  - Marine worms (genus Osedax) colonize cow bones.
AB  - Bone-eating worms of the genus Osedax colonized and grew on cow bones deployed at
      depths ranging from 385 to 2893m in Monterey Bay, California. Colonization
      occurred as rapidly as two months following deployment of the cow bones, similar
      to the time it takes to colonize exposed whalebones. Some Osedax females found on
      the cow bones were producing eggs and some hosted dwarf males in their tubes.
      Morphological and molecular examinations of these worms confirmed the presence of
      six Osedax species, out of the eight species presently known from Monterey Bay.
      The ability of Osedax species to colonize, grow and reproduce on cow bones
      challenges previous notions that these worms are 'whale-fall specialists.'

PMID- 18077257
TI  - Seasonality, cohort-dependence and the development of immunity in a natural host
      nematode system.
AB  - Acquired immunity is known to be a key modulator of the dynamics of many helminth
      parasites in domestic and human host populations, but its relative importance in
      natural populations is more controversial. A detailed long-term dataset on the
      gastrointestinal nematode Trichostrongylus retortaeformis in a wild population of
      European rabbits (Oryctolagus cuniculus) shows clear evidence of seasonal
      acquired immunity in the age-structured infection profiles. By fitting a
      hierarchy of demographic infection-immunity models to the observed age-structured
      infection patterns, we are able to quantify the importance of different
      components (seasonality, immunity and host age structure) of the parasite
      dynamics. We find strong evidence that the hosts' immunocompetence waxes and
      wanes with the seasons, but also contains a lifelong cohort factor, possibly
      acting through a maternal effect dependent on the host's month of birth. These
      observations have important and broad implications for the ecology of parasite
      infection in seasonal natural herbivore systems.

PMID- 18077258
TI  - Dispersal without errors: symmetrical ears tune into the right frequency for
      survival.
AB  - Vertebrate animals localize sounds by comparing differences in the acoustic
      signal between the two ears and, accordingly, ear structures such as the otoliths
      of fishes are expected to develop symmetrically. Sound recently emerged as a
      leading candidate cue for reef fish larvae navigating from open waters back to
      the reef. Clearly, the integrity of the auditory organ has a direct bearing on
      what and how fish larvae hear. Yet, the link between otolith symmetry and
      effective navigation has never been investigated in fishes. We tested whether
      otolith asymmetry influenced the ability of returning larvae to detect and
      successfully recruit to favourable reef habitats. Our results suggest that larvae
      with asymmetrical otoliths not only encountered greater difficulties in detecting
      suitable settlement habitats, but may also suffer significantly higher rates of
      mortality. Further, we found that otolith asymmetries arising early in the
      embryonic stage were not corrected by any compensational growth mechanism during
      the larval stage. Because these errors persist and phenotypic selection penalizes
      asymmetrical individuals, asymmetry is likely to play an important role in
      shaping wild fish populations.

PMID- 18077259
TI  - Factors influencing depressive symptoms of children treated for a brain tumor.
AB  - OBJECTIVES: To examine depressive symptoms in children treated for a brain tumor
      and related clinical, demographic and personal factors. METHODS: Fifty-four
      children with brain tumors (32 males) aged 8.2-18.3 years participated.
      Standardized measures assessed depressive symptoms, social skills, self-worth and
      IQ. Clinical (treatment) and demographic variables (gender) were also examined.
      RESULTS: Depression scores were subjected to a 2 (gender), X 2 (social skills:
      low, high), X 3 (self-worth: low, average, high) ANCOVA with IQ as the covariate.
      Significant main effects of gender and of self-worth and an interaction between
      gender, social skills, and self-worth were observed. Gender was identified as a
      moderator of the effect of social skills and self-worth on depressive symptoms.
      CONCLUSIONS: Gender, social skills, and self-worth play important roles in the
      depressive symptoms of pediatric brain tumor patients.

PMID- 18077260
TI  - Do cancer follow-up consultations create anxiety?
AB  - INTRODUCTION: Recent literature has suggested that follow- up visits provide
      psychological support for patients with cancer, but largely without objective
      evidence. AIMS: To examine the psychological impact of follow-up consultations on
      cancer patients and identify factors that influence patient anxiety. METHODS:
      Patients attending a routine follow-up at Liverpool Cancer Therapy Centre were
      surveyed. Using the State & Trait Anxiety Inventory (STAI), anxiety scores were
      obtained before and after consultation. RESULTS: Two hundred and thirty-one
      patients participated, 199 patients were treated with curative intent, 62% were
      male. The mean anxiety score was higher in females and in palliative cases. Lower
      levels of social support, poor perception of own health and receiving bad news
      during consultation were associated with higher STAI scores. Satisfaction with
      cancer treatment was associated with lower STAI scores. There was a small but
      statistically significant reduction of anxiety scores after consultation (p =
      0.02). CONCLUSIONS: When measured objectively, specialist consultation appears to
      have a small, but statistically significant, positive impact on the level of
      patient anxiety. Patient satisfaction correlated well with the patient anxiety
      levels.

PMID- 18077261
TI  - The phenomenology and screening of clinical depression in cancer patients.
AB  - Clinical depression is the most common psychiatric disorder among cancer patients
      and is associated with significant functional impairment. Unfortunately,
      depression in cancer patients is often under- diagnosed and untreated, and
      studies examining the predictive utility of assessment instruments in detecting
      clinically depressed cancer patients are sparse. Using a structured interview,
      thirty-three patients with various cancer types were diagnosed as having major
      depression (n = 24) or no psychiatric diagnosis (n = 9). All patients were
      administered the Beck Depression Inventory-II (BDI-II), the Center for
      Epidemiological Studies in Depression Scale (CES-D), Hamilton Rating Scale for
      Depression (HRSD), Quality of Life Inventory (QOLI), a medical and psychosocial
      functioning questionnaire (SF-36), and given co-morbidity of depression with
      anxiety disorders, the Beck Anxiety Inventory (BAI). Depressed and non-depressed
      cancer patients were compared and contrasted across all assessment measures and
      accuracy of instruments was based on evaluating their sensitivity, specificity,
      and positive predictive values. Depressed cancer patients exhibited more severe
      depressive symptoms and poorer quality of life, increased anxiety and bodily
      pain, and decreased vitality and social functioning. All instruments exhibited
      strong predictive properties, with the CES-D and BDI-II considered most feasible
      given their time efficiency, administrative simplicity, and strong psychometric
      properties.

PMID- 18077262
TI  - How patients with less-advanced and more-advanced cancer deal with three death
      related fears: an exploratory study.
AB  - The means used by cancer patients to cope with each of three death anxieties
      (i.e., fear of pain and suffering, loneliness, and the unknown) that contribute
      to their psychological distress have rarely been examined. Differences between
      cancer patients with Stage I or II disease (Group 1) and Stage III or IV disease
      (Group 2) were explored. T-tests revealed no difference between the groups. Age
      controlled Pearson correlations were used to determine the relationship between
      all three death anxieties, and some recognized coping devices used by cancer
      patients, namely, coping styles, optimism, and religiosity/spirituality. Results
      showed that, for Group 1, avoidant coping correlated positively with fear of the
      unknown, and social diversion correlated positively with fear of pain and
      suffering. As for similarities between groups, with the exception of fear of pain
      and suffering for Group 2, emotion-focused coping correlated positively with all
      three death anxieties, and optimism correlated negatively with fear of the
      unknown. The advantage for researchers and clinicians of including measures or
      evaluation of the death anxieties in their considerations of the psychological
      distress of cancer patients is discussed.

PMID- 18077263
TI  - Psychosocial factors in lung cancer: quality of life, economic impact, and
      survivorship implications.
AB  - Lung cancer is the leading cause of cancer mortality in men and women. Lung
      cancer accounts for approximately 30% of all cancer deaths in the United States.
      In addition, it is the most often diagnosed cancer in men, and the second most
      often diagnosed cancer in women. Five-year survival rates in lung cancer remain
      very low, around 15%. Approximately 45% of patients present with stage III
      disease. The majority of these patients are considered non-resectable, leading to
      the poor survival statistics seen in this disease. Unfortunately, survival rates
      have not improved in the past 30 years despite much research in diagnostics and
      therapeutics. Patients with advanced disease often experience multiple symptoms,
      including fatigue, pain, dyspnea, cough, hemoptysis, and anorexia. This paper
      will review the enormous toll that lung cancer takes on society, as well as
      individuals and families affected. In addition, we will examine psychosocial
      factors pertinent to lung cancer. Specifically, the article briefly discusses
      treatment approaches to lung cancer, as they relate to quality of life (QOL). QOL
      as a construct within lung cancer is then reviewed. Comment is made on the
      evaluation and prognostic importance of QOL. Next, economic and survivorship
      aspects of lung cancer are discussed. Finally, a summary of relevant psychosocial
      interventions for patients diagnosed with lung cancer is given.

PMID- 18077264
TI  - Identifying supportive and unsupportive responses of others: perspectives of
      African American and Caucasian cancer patients.
AB  - This study uses focus group methodology to examine supportive and unsupportive
      responses experienced by African American and Caucasian cancer patients.
      Supportive responses included practical assistance, as well as people's
      willingness to listen, maintain a positive attitude, and pray. Unsupportive
      responses included others' withdrawal behaviors, patients having to support
      friends/family as they coped, and family/friends limiting patients' independence.
      Results reflect ways in which mental health providers, social workers, and health
      care providers can help patients express support needs, as well as how social
      networks can be better educated about the types of support valued by patients.

PMID- 18077265
TI  - The legacy of cancer: the importance of passing on beliefs, values and positive
      health behaviors for women with cancer.
AB  - This article describes results from a qualitative study that explored the role
      and function of legacy in the lives of women cancer survivors. Legacy emerged as
      the passing on of values and beliefs. The results were derived from information
      gathered from in-depth interviews with 14 women aged 31-81 years, diagnosed with
      cancer. The interviews collected information related to what the women wanted
      their legacy to be, and how and to whom they hope to transmit it. Analysis of the
      interviews was guided by a typology of three distinct but overlapping categories
      of legacy: Legacy of Belongings, Legacy of Body, and a Legacy of Being (Hunter &
      Rowles, 2005). One recurring theme from the interviews was the hope that family
      members would learn from the experiences of the participants and would adopt
      positive health behaviors and cancer screening. The findings suggest that
      addressing legacy interests and opportunities may be an important tool for
      addressing needs of cancer survivors.

PMID- 18077267
TI  - Intimate partner abuse of older men: considerations for the assessment of risk.
AB  - Intimate partner abuse among older persons, though less common than among the
      general population, is a significant concern. Drawing from the intimate partner
      abuse and elder abuse literatures, this paper presents considerations for the
      assessment of risk for intimate partner abuse perpetrated against older men, with
      reference to the prevalent gendered view of abuse between intimate partners.
      Potential victim and perpetrator risk factors specific to this context are
      discussed and existing risk assessment tools are introduced. Implications and
      future research directions are discussed with regard to the application of risk
      assessment technology to this context.

PMID- 18077268
TI  - From behind the shadows: a profile of the sexual abuse of older men residing in
      nursing homes.
AB  - Previous research on the sexual abuse of older adults has revealed few cases of
      the sexual abuse of older men. The first national study of the sexual abuse of
      vulnerable adults in facilities, reported in this article, collected data on
      alleged, investigated, and substantiated cases of sexual abuse. This study
      revealed 26 cases reported and screened in for investigation concerning the
      alleged sexual abuse of older men (aged 50 and older) residing in nursing homes.
      Cases occurred in five states within a six month time period. Of these cases, six
      were confirmed upon investigation by Adult Protective Services or other
      regulatory agencies. Victims tended to be predominantly white males with
      cognitive and physical deficits that limited their ability for self care. The
      most typical sexual abuse alleged and substantiated was fondling. Residents were
      more often substantiated as the abuser than other perpetrators. Sexual abuse of
      older men in nursing homes crosses traditional gender, cultural, and role
      boundaries for both victims and perpetrators.

PMID- 18077269
TI  - Detection and prevalence of abuse of older males: perspectives from family
      practice.
AB  - Family doctors' frequent contact with seniors put them in reasonable positions to
      detect elder abuse and initiate referral to adult protective services. Since
      doctor reporting is low, however, this paper explores whether the gender of
      patient and/or doctor impacts on identification of elder mistreatment, or creates
      differential detection of one gender over the other. Use of the validated Elder
      Abuse Suspicion Index (EASI), and a structured social work evaluation, is
      described to provide some gender-based data from Canadian family practice.
      Specifically, while the prevalence of elder abuse is estimated to range from
      12.0% to 13.3%, the specific prevalence was found for females to be 13.6% to
      15.2% and for males 9.1% to 9.7%.

PMID- 18077270
TI  - Osteoporosis: an invisible, undertreated, and neglected disease of elderly men.
AB  - This article highlights a silent disease that threatens the health and vitality
      of older men. Among elderly men and women, osteoporosis is among one of the
      leading causes of morbidity and mortality in the United States. Once perceived as
      only a female dominated disease, osteoporosis is now known to be gender blind.
      The following discussion will review the epidemiology and pathology of
      osteoporosis, and identify the concerns raised for men, including neglect.
      Special management considerations for older men and recommendations for future
      research into this overlooked major health problem will be explored. Better
      understanding of how osteoporosis affects older men may help to encourage
      prevention strategies earlier in life, appropriate screening and monitoring, as
      well as more effective treatment later in life.

PMID- 18077271
TI  - Fractured relationships and the potential for abuse of older men.
AB  - Elderly men are an understudied population in the area of abuse and neglect. The
      typical elder abuse or neglect victim is described as a frail woman. The National
      Elder Abuse Incidence Study shows men to be victims as well and at higher risk
      than women for abandonment, the most extreme form of neglect. A qualitative study
      of older widowed men did not specifically explore issues of abuse and neglect,
      but found several of the men experiencing alienation from one or more of their
      adult children. This paper explores the dynamics of these "fractured
      relationships" and finds several patterns that may increase an older man's risk
      of being neglected when his needs for support increase. Many men are not
      functioning in a kinkeeper role and are not attempting to repair fractured
      relationships. Minimizing their own feelings may prevent men from understanding
      the extent of alienation felt by an adult child.

PMID- 18077272
TI  - Notes on newspaper accounts of male elder abuse.
AB  - Law enforcement press releases and other print-media miscellany detailing
      accounts of male elder abuse involving insurance fraud, false allegations by
      perpetrators, and abuse inflicted by caregivers, spawned interest in a more
      systematic review. That review was accomplished principally by accessing two
      search engines, with news articles from 1986 to the present. A review of these
      media accounts transformed the initial "insurance fraud" category into a broader
      one classified as "economic exploitation." That same review also resulted in
      three distinctive categories of caregiver abuse. This article provides
      abbreviated case accounts within each category, and concludes with brief notes on
      several themes derived from the reported accounts.

PMID- 18077273
TI  - Identifying and working with older male victims of abuse in England.
AB  - The abuse of men is still very much a taboo subject, so identifying older men who
      have been abused in childhood or adulthood can be very difficult. This paper
      discusses the problems in identifying older male victims by drawing on the
      findings of two research projects. Statistical evidence is presented regarding
      the victims and the abuse they have experienced. It is argued that in general
      resources are not readily available to facilitate disclosure or to help men
      through the healing process. An example of good practice is presented by
      discussing the work undertaken with an older man through group work.

PMID- 18077274
TI  - Gendered policies and practices that increase older men's risk of elder
      mistreatment.
AB  - We aim to detail some of the ways that social policy and gendered practices put
      older men at risk of elder mistreatment. Research on the abuse and neglect that
      older adults experience has often focused on the characteristics of the victims
      and the dynamics within families, emphasizing factors such as the likelihood of
      an intergenerational cycle of violence, substance abuse and dependency, and older
      men's financial status as key risks in elder abuse. The effect on men from this
      type of analysis is that elder mistreatment remains an individual or family
      problem rather than being viewed as a larger societal concern. This article
      challenges the individualistic focus by outlining the importance of societal
      forces affecting older men's risk of mistreatment.

PMID- 18077275
TI  - Intervention with abused older males: conceptual and clinical perspectives.
AB  - Men and women experience abuse in different ways and older men have particular
      treatment needs that must be addressed by clinicians. The current design and
      configuration of clinical services may create barriers to abused older men
      receiving treatment fully suited to their needs. In this article, the unique
      experiential dynamics and help seeking behaviors of older men who experience
      abuse are delineated and recommendations are given for structuring services to
      better meet their needs. Gender-sensitive clinical techniques and modalities are
      described and suggestions for interventions that could prove particularly
      efficacious in the treatment of older men are offered.

PMID- 18077276
TI  - Abuse of elderly male client: efforts and experiences in rural and urban adult
      protective services.
AB  - Elder abuse has not been viewed as seriously as child abuse because of the
      emotional sensibilities attached to child abuse. Although elder abuse is
      experienced disproportionately by women, men also are in need of protection and
      engagement. An important factor for understanding the work with elderly men is
      the social construction of manhood. Both urban and rural settings recognize this
      as a significant starting point to engage men in services. This paper describes
      the efforts in both rural and urban Adult Protective Service agencies to identify
      and work with abused elderly men from a strengths and solution-focused
      perspective.

PMID- 18077277
TI  - Exploring trends: tracking evaluations data over several months by therapists and
      parents of children with cerebral palsy.
AB  - A pilot study was conducted at the outpatient rehabilitation unit of a children's
      hospital to explore the overall performance trends of children in daily life as
      perceived by their parents, compared to the evaluations of therapists. A
      performance goal was set for each child by his/her therapist and parent at an
      initial consultation. Over a six-month period, data were collected from the
      parents of children with cerebral palsy (N = 53), and therapists assessed
      children at each therapy session as well. The evaluations of both parents and
      therapists showed statistically significant upward trends in performance over
      several months.

PMID- 18077278
TI  - Complexities in attracting and retaining direct support professionals.
AB  - Recruiting and retaining direct support professionals (DSPs) remains essential to
      the full inclusion for persons with disabilities. Using a mixed-evaluation model,
      we measured DSPs' views versus those of their supervisors. DSPs expressed lower
      perceptions concerning their supervisors, satisfaction with their work situation,
      and environmental and safety factors. Focus groups provided insights into
      resolving issues related to compensation, work environment, and recruiting and
      retaining future DSPs. Motivating factors included wanting to be part of a
      helping community where all are valued. To improve their performance, DSPs stated
      their desire to understand the roles of managers and of the consumer. DSPs
      indicated that having career paths that provided advancement opportunities and
      direct contact with persons with disabilities were primary motivators.

PMID- 18077279
TI  - Supporting the well-being of people with mobility disabilities through social
      work practice.
AB  - The purpose of this insight generating study was to explore the viewpoints of
      people with mobility disabilities (PWMD) about ways for social workers to promote
      their well-being through social work practice. A qualitative participant action
      style methodology encouraged PWMDto voice their concerns and recommendations.
      Eighteen PWMD were interviewed, including nine consumers and nine social workers.
      Participants indicated from their experiences that social workers commonly are
      not sufficiently cognizant of the personal goals, perspectives, and health
      potentials of PWMD. Overall, they suggested that the social work practice
      approach for people with disabilities should become more holistic and proactive.
      Their recommendations are consistent with current ideas about best practice in
      the social work and disabilities literature and they reinforce the importance of
      making these ideas more widely practiced.

PMID- 18077280
TI  - Self- and caregiver-reported experiences of young adults with developmental
      disabilities.
AB  - The purpose of this study was to describe the experiences of young adults with
      developmental disabilities (DD) who were living in community settings with the
      aid of government-supported services. Six male and 10 female volunteer subjects
      (mean age = 24 years) were interviewed and the narrative data were analyzed
      revealing themes in six categories: (1) Home Life, (2) Relationships, (3) Health
      and Health Care, (4) Personal Growth and Accomplishments, (5) Occupation, and (6)
      Transportation. Subjects' most positive experiences were associated with
      integrated, comprehensive and timely services delivered by knowledgeable and
      sensitive service providers. Strong parental advocacy facilitated these features.
      Additionally, experiences were most positive when daily activities occurred
      within the sphere of either family or the disability community, as opposed to the
      broader community. Research is suggested to further understand the dynamics of
      integration in the broader community and to devise strategies to successfully
      facilitate this integration.

PMID- 18077281
TI  - What are students learning about trauma, memory, and dissociation?

PMID- 18077282
TI  - A multi-modal treatment program for childhood trauma recovery:Women Recovering
      from Abuse Program (WRAP).
AB  - This article describes the Women Recovering from Abuse Program (WRAP), an
      outpatient day-hospital program for women suffering from the sequelae of
      childhood abuse. WRAP was conceived in 1998 by clinicians who advocated for its
      development based on a growing need to provide women who had experienced
      childhood trauma an alternative to an inpatient program. WRAP draws from a Stage
      1 treatment approach to address chronic interpersonal trauma and dissociation by
      incorporating psychopharmacology, individual and group psychotherapy. The program
      is structured into two phases: a preparatory Building Resources Group (BRG) and
      an intensive multimodal segment comprised of seven types of group therapy. Each
      group is described in terms of the treatment rationale and its structure and
      process. Two research studies to date support the effectiveness of WRAP.

PMID- 18077283
TI  - Childhood maltreatment and revictimization: the role of affect dysregulation,
      interpersonal relatedness difficulties and posttraumatic stress disorder.
AB  - In this study, posttraumatic stress disorder (PTSD) and other posttraumatic
      sequelae, including affect dysregulation and problems with interpersonal
      relatedness, were examined as potential predictors of revictimization. Data were
      analyzed for 207 individuals who reported childhood maltreatment per the Child
      Maltreatment Interview Schedule. Participants included prison inmates, a
      treatment-seeking community sample, and a sample recruited via the internet.
      Significant gender differences were found for rates of revictimization.
      Controlling for the effects of childhood maltreatment, PTSD significantly
      predicts sexual revictimization of women. Interpersonal relatedness problems
      enter as a predictor for most types of revictimization of women, and indices
      reflective of affect dysregulation variably predict the different types of
      revictimization examined in this study. doi:10.1300/J229v08n04_03.

PMID- 18077284
TI  - Fostering internal cooperation through the use of imagery in the treatment of
      dissociative identity disorder.
AB  - Most clinicians working with dissociative identity disorder (D.I.D.) recognize
      the importance of working towards a cooperative system especially during the
      initial stages of treatment. However, achieving this can be a monumental task
      given the inner war that goes on inside the mind of an individual diagnosed with
      D.I.D. From an ego-state theoretical framework, this article will demonstrate
      through clinical cases and artwork, the value of imagery techniques in changing
      internal perceptions, especially with regards to introject ego states. These
      changes can assist in eliciting more internal cooperation, a necessary task prior
      to working towards a collaborative, co-conscious system or what some theorists
      would call integration.

PMID- 18077285
TI  - Functional dissociation of the self: a socio-cognitive approach to trauma and
      dissociation.
AB  - A novel socio-cognitive theory of dissociation and dissociative disorders is
      proposed. The model, which is both theoretical and clinical, is based on
      "functional dissociation of the self." A new concept is introduced in this paper:
      the sociological self. While the sociological self may have cultural and societal
      dimensions, it is regarded here as a universal phenomenon rather than a culture
      bound one; as an individual psychological instance rather than a sociological
      concept per se. It is proposed that the main sources of dissociation are trauma
      related detachment of the sociological and psychological selves and the
      subsequent amplification of the sociological self. Thus, effective psychotherapy
      must curtail the enlargement of the sociological self and reactivate the
      psychological self. It is hoped that this conceptualization will contribute to
      efforts both toward understanding the everyday dissociation of the average
      contemporary individual and toward developing novel psychotherapeutic approaches
      which might shorten the length of treatment of dissociative disorders.

PMID- 18077286
TI  - The role of ethnic identity in the relationship of race-related stress to PTSD
      symptoms among young adults.
AB  - Although many studies have shown that stronger ethnic identity is associated with
      better adjustment, the role of ethnic identity in the context of race-related
      threat is unclear. The purpose of this study was to examine the effect of ethnic
      identity on the severity of posttraumatic stress disorder (PTSD) symptoms in the
      context of race-related stress, particularly to examine whether ethnic identity
      moderates the effect of racism on consequent PTSD symptoms. Subjects were 91
      undergraduate students (11% Caucasian, 6.6% African American, 18.7% Hispanic,
      47.3% Asian, 5.5% Middle Eastern, and 8.8% Other) who reported experiences of
      race-related stress. Race-related stress, ethnic identity, and PTSD symptoms were
      assessed through self-report measures. Results of a simultaneous multiple
      regression indicated that ethnic identity moderated PTSD symptoms in response to
      perceived racism, such that stronger ethnic identity was associated with more
      PTSD symptoms in the face of increasing levels of race-related stress.
      Additionally, race-related stress independently predicted PTSD symptoms. These
      results are consistent with previous findings that ethnic identity increases the
      experience of distress in the context of self-relevant threat.

PMID- 18077288
TI  - Dissociation: the art and the science, twenty-two years later.

PMID- 18077293
TI  - A different kind of holding environment: a case study of group work with
      pediatric staff.
AB  - This paper reports a nearly two-year intervention with staff at a major urban
      pediatric facility. The authors worked as trainers and consultants for two groups
      the Emergency Department (ED) and Chronic Care units (CC). Following two days of
      training about grief and loss, highlighting skill building for work with
      traumatized and grieving children and parents, the consultants worked to develop
      teams which could provide a Winnicottian holding environment for staff. The
      efficacy of this staff training is analyzed and support needs of staff members
      are identified. Findings include varied willingness to make use of group support.
      Chronic care participants are more likely to express willingness to engage in on
      going support for one another, while ED staff members seem to prefer structured,
      educational training and episodic support. The holding environment of the
      processing groups must be adapted to fit the needs of the medical sub-culture.

PMID- 18077294
TI  - The impact of peer death on adolescent girls: a task-oriented group intervention.
AB  - Adolescents' exposure to death is high, with approximately 40% of adolescents
      reporting past year death of a peer. Each of the estimated annual 14,000 deaths
      of adolescents has an impact on friends, classmates, and peers, with adolescent
      girls experiencing more peer deaths within a one year time frame than boys. Much
      of the literature focuses on parent or sibling death but little on the death of a
      peer. The sudden and unexpected nature of adolescent deaths appears to be a
      common experience that deeply affects adolescent girls and puts them at risk for
      a wide range of negative physical, emotional, social, and cognitive outcomes. The
      author outlines a task-oriented group intervention that meets the developmental,
      emotional, cognitive, and gender-specific needs of adolescent girls grieving the
      death of a peer.

PMID- 18077295
TI  - Comfort and confidence levels of health care professionals providing pediatric
      palliative care in the intensive care unit.
AB  - Most childhood deaths that occur in the hospital happen in the pediatric
      intensive care unit. Providing pediatric palliative care in the intensive care
      unit comes with unique challenges due to the acute care, curative and often
      medically aggressive focus of these settings. In this study, 190 PICU health care
      professionals reported on their comfort and confidence in providing palliative
      care. Findings indicate that professionals report only a moderate level of
      comfort and confidence in this type of care in the pediatric ICU. For physicians
      and nurses, comfort and confidence was significantly higher for those who had
      practiced 8 years or more. Practitioners reported less comfort in providing
      psychosocial care. Implications for the social work role on the interdisciplinary
      team and suggestions for future research are discussed.

PMID- 18077296
TI  - Stillbirth: the mother's experience and implications for improving care.
AB  - More children die as a result of stillbirth than all other causes of infant
      deaths combined (Ananth, Shiliang, Kinzler, and Kramer, 2005; Goldenberg, Kirby,
      and Culhane, 2004; Froen, 2005; National Institute of Health, 2004); yet, mothers
      experiencing stillbirth are often left without support afterwards (Kubler-Ross,
      2004; Fahey-McCarthy, 2003; Fletcher 2002; Saddler, 1987; DeFrain, 1986; Kirkley
      Best & Kellner, 1982). Despite social work's growing involvement in care at the
      end of life, parents of stillborn children have not experienced consistent,
      relevant, and competent professional care in coping with the tragedy of death.
      Forty-seven women between the ages of 19 and 51 were recruited through nonprofit
      agencies that provide bereavement care to grieving families. Results of this
      qualitative study suggest that stillbirth is emotionally complex with long
      lasting symptoms of grief and significant struggles to find meaning. The findings
      also support the need for perceived psychosocial and spiritual support from
      professional caregivers, family, and friends. The women's own experiences argue
      for comprehensive approaches to support the grief and loss of stillbirth, and for
      the importance of social work involvement in both immediate and longer term
      interventions.

PMID- 18077297
TI  - Social work, siblings, and SIDS: conceptual and case-based guidance for family
      system intervention.
AB  - Sudden Infant Death Syndrome (SIDS) is a tragic loss event within the family,
      impacting adults as well as children. This article uses three case illustrations
      to discuss the role of a SIDS event on the family system with a special focus on
      the emergent challenges for surviving siblings of various ages. Practice
      application examples are woven throughout the review to illustrate the age
      specific grief responses which may occur following a SIDS event. The article also
      presents a theoretically supported intervention matrix that integrates models of
      bereavement support and family system responses, taking into account children's
      varying developmental needs and tasks based on sibling age.

PMID- 18077298
TI  - Introduction: screening and brief intervention.

PMID- 18077299
TI  - Screening and brief intervention enter their 5th decade.
AB  - About 40 years since the first controlled study, screening and brief intervention
      (SBI) are being disseminated into practice. But many unanswered questions remain.
      Studies in this special issue address what we know and don't know about alcohol
      and drug SBI, cost-effectiveness, patient preferences, education for clinicians,
      quality performance measures, 'no-contact' SBI, predictors of behavior change,
      and methodological concerns with the SBI literature. The best evidence for
      efficacy of SBI is that it can lead to decreased consumption in primary care
      patients with non-dependent unhealthy alcohol use. But further research is needed
      on brief drug screening tools, efficacy of SBI for drugs, effectiveness in real
      world settings, integration of SBI for alcohol and drugs with other health
      behaviors, effects of SBI on alcohol and drug consequences, effects on dependence
      among those not seeking help, and on how to best disseminate the efficacious
      elements of SBI into practice.

PMID- 18077300
TI  - Screening, Brief Intervention, and Referral to Treatment (SBIRT): toward a public
      health approach to the management of substance abuse.
AB  - Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a
      comprehensive and integrated approach to the delivery of early intervention and
      treatment services through universal screening for persons with substance use
      disorders and those at risk. This paper describes research on the components of
      SBIRT conducted during the past 25 years, including the development of screening
      tests, clinical trials of brief interventions and implementation research.
      Beginning in the 1980s, concerted efforts were made in the US and at the World
      Health Organization to provide an evidence base for alcohol screening and brief
      intervention in primary health care settings. With the development of reliable
      and accurate screening tests for alcohol, more than a hundred clinical trials
      were conducted to evaluate the efficacy and cost effectiveness of alcohol
      screening and brief intervention in primary care, emergency departments and
      trauma centers. With the accumulation of positive evidence, implementation
      research on alcohol SBI was begun in the 1990s, followed by trials of similar
      methods for other substances (e.g., illicit drugs, tobacco, prescription drugs)
      and by national demonstration programs in the US and other countries. The results
      of these efforts demonstrate the cumulative benefit of translational research on
      health care delivery systems and substance abuse policy. That SBIRT yields short
      term improvements in individuals' health is irrefutable; long-term effects on
      population health have not yet been demonstrated, but simulation models suggest
      that the benefits could be substantial.

PMID- 18077301
TI  - Methodological issues in alcohol screening and brief intervention research.
AB  - The research literature on screening and brief intervention (SBI) for unhealthy
      alcohol use is large and diverse. More than 50 clinical trials and 9 systematic
      reviews have been published on SBI in a range of healthcare settings, and via a
      variety of delivery approaches, in general practice, hospital wards, emergency
      departments, addiction treatment centres, and more recently, via computers and
      the Internet. The aim of this paper was to discuss methodological issues which
      arise in the design, analysis, interpretation, and reporting of SBI trials.
      Principal among these are the challenge of detecting small effects, standards of
      analysis, reporting, and interpretation, the risks of bias arising from self
      report of outcomes, and the need to ensure that results have the potential to be
      applied in practice to reduce the burden of disease and injury attributable to
      unhealthy alcohol use.

PMID- 18077302
TI  - Communication during brief intervention, intention to change, and outcome.
AB  - OBJECTIVES: To explore the relationship between patient's intention to change
      regarding future alcohol consumption following brief alcohol intervention (BAI)
      and changes in alcohol consumption 12-months later and the communication
      characteristics between patient and counselor during BAI. DESIGN, SETTING AND
      SUBJECTS: Data from 367 patients (experimental arm) of a pragmatic randomized
      controlled trial were used to assess the effectiveness of BAI among hazardous
      drinkers attending an Emergency Department (Lausanne University Hospital,
      Lausanne, Switzerland). Alcohol outcome measures at baseline and 12 months follow
      up included usual number of drinks per week, monthly frequency of heavy episodic
      drinking (5 or more standard drinks for men; 4 or more for women), and the
      Alcohol Use Disorders Identification Test (AUDIT) score. In addition, the
      communication characteristics between patient and counselor were analyzed via
      tape recordings using the Motivational Interviewing Skill Code (MISC) from 97
      participants. Patient readiness and importance to change on a 10-point Likert
      scale (readiness/importance to change ruler) was asked during BAI, and patient
      intention to change alcohol consumption (yes/no) was asked at the last step.
      Differences in alcohol outcome at follow-up between the 367 patients who did or
      did not have an intention to change consumption at baseline were compared, as
      were differences between these two groups in communication characteristics for
      the 97 who completed tape recordings. RESULTS: Patients with an intention to
      decrease alcohol consumption reduced alcohol use and related problems more often,
      and reported higher levels of importance and readiness to change than did their
      counterparts. Analyses of MISC-coded data showed a significantly higher use of MI
      consistent skills among those with a moderation intention, but no group
      differences on the 8 other counselor communication skills measures were found.
      Analyses of patient speech during the intervention indicated that those with an
      intention to change their alcohol consumption significantly more often self
      explored personal ambivalence towards alcohol, expressed more intensely their
      ability, commitment, desire, need and reason to change their alcohol use than did
      those in the no decrease group. CONCLUSIONS: The intention expressed by hazardous
      drinkers when concluding BAI is associated with both patient change talk during
      BAI and drinking outcome 12 months later, but is mainly independent of counselor
      communication skills. This intention may be an important clinical indicator of
      which hazardous drinkers are most likely to improve after BAI.

PMID- 18077303
TI  - Examining quality issues in alcohol misuse screening.
AB  - The Veterans Health Administration (VHA) has successfully implemented evidence-
      based alcohol misuse screening with the AUDIT-C. The purpose of this study was to
      evaluate clinical alcohol screening during the first year after implementation.
      Using medical record review and mailed patient surveys collected during 2004 by
      VHA Office of Quality and Performance, this study analyzed concordance of
      screening results among patients with AUDIT-Cs in both data sources. Among 1,637
      patients with AUDIT-C from both sources within 90 days, the medical record
      screening prevalence rate of alcohol misuse, 24.6% (95% CI: 22.5% to 26.7%), was
      significantly lower than the survey rate, 33.4% (31.1% to 35.7%). Of 8,312
      patients identified as nondrinkers in medical records, 24% reported past year
      alcohol use and 5% screened positive for alcohol misuse on surveys. Lower rates
      of alcohol use and misuse documented in medical records compared to mailed
      surveys suggest further investigation and standardization of clinical screening
      are necessary.

PMID- 18077304
TI  - The cost-effectiveness and cost-benefit of screening and brief intervention for
      unhealthy alcohol use in medical settings.
AB  - Economic evaluation can be a valuable tool for assessing the efficiency and value
      of health care programs. To examine the literature on the economic evaluation of
      alcohol screening and brief intervention in medical settings, relevant studies
      were identified in the MEDLINE database (1966 through November 2006) and by hand
      searching the references of identified articles and relevant journals. The 15
      identified studies used a range of economic evaluation methods, including cost
      analysis, cost-benefit, cost-effectiveness, and cost-utility. Nearly all of the
      studies supported the use of alcohol screening and brief intervention. The
      studies that prospectively collected cost and effect data and/or conformed
      closely to methodological guidelines demonstrated a strong economic benefit of
      alcohol screening and brief intervention when compared to usual care. Overall,
      the reviewed studies support alcohol SBI in medical settings as a wise use of
      health care resources and illustrate the usefulness of economic evaluation for
      assessing alcohol prevention and treatment programs.

PMID- 18077305
TI  - An evidence based alcohol screening, brief intervention and referral to treatment
      (SBIRT) curriculum for emergency department (ED) providers improves skills and
      utilization.
AB  - OBJECTIVE: Emergency Departments (EDs) offer an opportunity to improve the care
      of patients with at-risk and dependent drinking by teaching staff to screen,
      perform brief intervention and refer to treatment (SBIRT). We describe here the
      implementation at 14 Academic EDs of a structured SBIRT curriculum to determine
      if this learning experience improves provider beliefs and practices. METHODS: ED
      faculty, residents, nurses, physician extenders, social workers, and Emergency
      Medical Technicians (EMTs) were surveyed prior to participating in either a two
      hour interactive workshops with case simulations, or a web-based program
      (www.ed.bmc.org/sbirt). A pre-post repeated measures design assessed changes in
      provider beliefs and practices at three and 12 months post-exposure. RESULTS:
      Among 402 ED providers, 74% reported < 10 hours of prior professional alcohol
      related education and 78% had < 2 hours exposure in the previous year. At 3-month
      follow-up, scores for self-reported confidence in ability, responsibility to
      intervene, and actual utilization of SBIRT skills all improved significantly over
      baseline. Gains decreased somewhat at 12 months, but remained above baseline.
      Length of time in practice was positively associated with SBIRT utilization,
      controlling for gender, race and type of profession. Persistent barriers included
      time limitations and lack of referral resources. CONCLUSIONS: ED providers
      respond favorably to SBIRT. Changes in utilization were substantial at three
      months post-exposure to a standardized curriculum, but less apparent after 12
      months. Booster sessions, trained assistants and infrastructure supports may be
      needed to sustain changes over the longer term.

PMID- 18077306
TI  - Brief alcohol interventions and multiple risk factors in primary care.
AB  - Early identification and intervention of harmful/hazardous drinking in primary
      care are U.S. healthcare priorities. Traditionally, research has focused on
      designing interventions for patients in primary care who report hazardous/harmful
      alcohol use, even though it is likely for a patient to be at risk for multiple
      problems. This article has three major goals: (1) to present data highlighting
      the prevalence and co-variation of other risk factors with hazardous/harmful
      drinking, including data from a small descriptive study; (2) to review the
      literature on brief alcohol interventions designed to address multiple risk
      factors; and (3) to provide recommendations for future research. Despite data
      indicating primary care patients present with multiple risk factors, only a
      limited number of studies in the literature have investigated brief interventions
      addressing alcohol use and other risk factors. It is important for future
      research to expand brief alcohol interventions to include other risk factors as
      well.

PMID- 18077307
TI  - Adolescents' preference for substance abuse screening in primary care practice.
AB  - OBJECTIVE: To assess adolescents' preferences for substance abuse screening in
      primary medical care settings. DESIGN/METHODS: Twelve- to 18-year-old patients (N
      = 2133) arriving for routine care at a network of primary care sites completed an
      interview that included demographic items, the CRAFFT screen, and a questionnaire
      assessing preferences for screening method (paper questionnaire, computer, oral
      interview by nurse or doctor). A subgroup (n = 222) completed the CRAFFT directly
      on the computer. RESULTS: Across the entire sample, paper was the screening
      administration method most preferred (mean rank (MR) = 2.92, 95%CI 2.87-2.96) vs.
      computer (MR = 2.38, 2.33-2.43), nurse (MR = 2.43, 2.39-2.47), and doctor (MR =
      2.30, 2.25-2.35). Among the participants who received the screening on the
      computer, however, computer (MR = 3.08, 95%CI 2.42-2.52) was statistically tied
      with paper (MR = 2.88, 2.75-3.02) and both were ranked significantly higher than
      nurse (MR = 2.06, 1.94-2.17) and doctor (MR = 1.98, 1.82-2.14). The findings were
      similar for participants' reports of being "very likely" to be honest when
      answering substance abuse screening questions. CONCLUSIONS: Adolescents should
      ideally be screened for substance abuse using paper or computer questionnaires.

PMID- 18077308
TI  - 'No-contact' interventions for unhealthy college drinking:efficacy of
      alternatives to person-delivered intervention approaches.
AB  - Despite the development of brief efficacious interventions, they are not reaching
      a large proportion of college students who continue to drink in a manner that
      puts them at risk for harm. Recent efforts have attempted to address this issue
      through the development of brief alcohol interventions that may be more broadly
      disseminated to college students. Researchers have adapted a variety of
      approaches to print and computer-based modalities that do not require direct real
      time contact with an interventionist. The goal of this paper is to review the
      empirical evidence for the utility of these brief alcohol interventions that are
      delivered without direct real-time contact. A systematic review of this research
      suggests that 'no-contact' interventions are feasible and may have efficacy.
      Further research is needed to understand the duration of these effects,
      mechanisms of change, moderators of outcome, and how to enhance the effectiveness
      of these approaches.

PMID- 18077309
TI  - Measuring performance of brief alcohol counseling in medical settings:a review of
      the options and lessons from the Veterans Affairs (VA) health care system.
AB  - Brief alcohol counseling is a top US prevention priority but has not been widely
      implemented. The lack of an easy performance measure for brief alcohol counseling
      is one important barrier to implementation. The purpose of this report is to
      outline important issues related to measuring performance of brief alcohol
      counseling in health care settings. We review the strengths and limitations of
      several options for measuring performance of brief alcohol counseling and
      describe three measures of brief alcohol counseling tested in the Veterans
      Affairs (VA) Health Care System. We conclude that administrative data are not
      well-suited to measuring performance of brief alcohol counseling. Patient surveys
      appear to offer the optimal approach currently available for comparing
      performance of brief alcohol counseling across health care systems, while more
      options are available for measuring performance within health care systems.
      Further research is needed in this important area of quality improvement.

PMID- 18077310
TI  - Successful, multiresistant bacterial clones.
AB  - Multilocus sequence typing gives us unparalleled insights into the population
      biology of bacterial species, including those that cause healthcare-associated
      and/or community-acquired infections. For many of these species, we now recognize
      the existence of internationally prevalent clones, which are often resistant to
      multiple antibiotics.

PMID- 18077311
TI  - Intercontinental emergence of Escherichia coli clone O25:H4-ST131 producing CTX-M
      15.
AB  - BACKGROUND: Concomitant with the recent emergence of CTX-M-type extended-spectrum
      beta-lactamases (ESBLs), Escherichia coli has become the enterobacterial species
      most affected by ESBLs. Multiple locales are encountering CTX-M-positive E. coli,
      including specifically CTX-M-15. To gain insights into the mechanism underlying
      this phenomenon, we assessed clonality and diversity of virulence profiles within
      an international collection of CTX-M-15-positive E. coli. METHODS: Forty-one ESBL
      positive E. coli isolates from eight countries and three continents (Europe, Asia
      and North America) were selected for study based on suspected clonality.
      Phylogenetic group, ERIC2 PCR profile, O H serotype, AmpC variant and antibiotic
      susceptibility were determined. Multilocus sequence typing (MLST) and PFGE
      provided additional discrimination. Virulence potential was inferred by detection
      of 46 virulence factor (VF) genes. RESULTS: Thirty-six (88%) of the 41 E. coli
      isolates exhibited the same set of core characteristics: phylogenetic group B2,
      ERIC2 PCR profile 1, serotype O25:H4, AmpC EC6, ciprofloxacin resistance and MLST
      profile ST131. By PFGE, the 36 isolates constituted one large cluster at the 68%
      similarity level; this comprised 17 PFGE groups (defined at 85% similarity), some
      of which included strains from different countries. The 36 isolates exhibited
      highly (91% to 100%) similar VF profiles. CONCLUSIONS: We describe a broadly
      disseminated, CTX-M-15-positive and virulent E. coli clonal group with highly
      homogeneous virulence genotypes and subgroups exhibiting highly similar PFGE
      profiles, suggesting recent emergence. Understanding how this clone has emerged
      and successfully disseminated within the hospital and community, including across
      national boundaries, should be a public health priority.

PMID- 18077312
TI  - Comment on: Efficacy of liposomal amphotericin B for secondary prophylaxis of
      visceral leishmaniasis in HIV-infected patients.

PMID- 18077314
TI  - Activin receptor subunits in normal and dysfunctional adult human testis.
AB  - BACKGROUND: The cellular sites of activin action and its regulation in the normal
      and dysfunctional adult human testis are unknown. METHODS: Activin type I (ALK2
      and ALK4) and type II (ActRIIA and ActRIIB) receptors were detected using
      immunohistochemistry on Bouins fixed sections of normal, carcinoma in situ (CIS),
      seminoma, non-seminoma and gonadotropin-deprived human testis. ActRIIA mRNA was
      localized by in situ hybridization. RESULTS: ALK2, ALK4 and ActRIIB proteins were
      observed in Sertoli cells, spermatogonia and some spermatocytes within normal and
      gonadotropin-suppressed adult human testis; all three receptor subunits were also
      detected in CIS, seminoma and non-seminoma cells. ActRIIA immunoreactivity was
      faint to absent in the normal testis and in CIS and non-seminoma cells, whereas
      some seminoma cells displayed a strong signal. Also in contrast to the normal
      testis, a majority of spermatogonia and Sertoli cells in gonadotropin-deprived
      samples exhibited a strong ActRIIA immunohistochemical and in situ hybridization
      signal. CONCLUSIONS: Spermatogonia and Sertoli cells appear as the primary
      targets of activin action in the adult human testis. Changes in testicular
      function associated with altered hormone levels may enhance ActRIIA mRNA and
      protein synthesis, thus modifying signalling by activin or other TGFbeta ligands
      within specific cells of the seminiferous epithelium.

PMID- 18077315
TI  - Is alpha2-macroglobulin important in female stress urinary incontinence?
AB  - BACKGROUND: Loss of mechanical stability of the urethra and bladder is thought to
      be important in the development of stress urinary incontinence (SUI). The vaginal
      wall is the main supporting tissue for pelvic organs and changes in components of
      supporting tissues are known to be involved in the pathophysiology of SUI.
      METHODS: We evaluated changes in expression of alpha2-macroglobulin (alpha2-M), a
      protease inhibitor, in vaginal wall tissues from premenopausal women (aged 42-45
      years) with SUI (n = 28) compared with menstrual cycle-matched continent women
      (controls, n = 29). The distribution of alpha2-M in vaginal wall tissues and
      fibroblasts was analysed by immunohistochemistry and immunofluorescence.
      Expression levels of alpha2-M mRNA and protein was determined by relative real
      time quantitative PCR and enzyme-linked immunosorbent assay, respectively.
      Protease inhibition was measured to assess bioactivity. RESULTS: Vaginal wall
      tissues do express alpha2-M. Expression of alpha2-M mRNA and protein was
      significantly higher in tissues from controls compared to women with SUI in both
      proliferative and secretory phases (P < 0.05). Protease inhibitory activity of
      alpha2-M was significantly higher in tissues from controls compared to women with
      SUI in the secretory phase (P < 0.05), but we found no difference in the
      proliferative phase between groups. alpha2-M protein level was lower in the
      proliferative phase than the secretory phase in both controls and SUI patients,
      while for alpha2-M mRNA this was found only in controls. CONCLUSIONS: Decreased
      expression of alpha2-M mRNA and protein and protease inhibitory activity in the
      vaginal wall tissues of women with SUI may contribute to the development of SUI.

PMID- 18077316
TI  - Difference in signalling between various hormone therapies in endometrium,
      myometrium and upper part of the vagina.
AB  - BACKGROUND: Combined hormone treatments in post-menopausal women have different
      clinical responses on uterus and vagina; therefore, we investigated differences
      in steroid signalling between various hormone therapies in these tissues.
      METHODS: A total of 30 post-menopausal women scheduled for hysterectomy were
      distributed into four subgroups: control-group (n = 9), Tibolone-group (n = 8);
      estradiol (E(2))-group (n = 7); E(2) + medroxyprogesterone acetate (MPA)-group (n
      = 6). Medication was administered orally every day for 21 days prior to removal
      of uterus and upper part of the vagina. Tissue RNA was isolated, and gene
      expression profiles were generated using GeneChip technology and analysed by
      cluster analysis and significance analysis of microarrays. Apoptosis and cell
      proliferation assays, as well as immunohistochemistry for hormone receptors were
      performed. RESULTS: 21-days of treatment with E(2), E(2) + MPA or tibolone
      imposes clear differential gene expression profiles on endometrium and
      myometrium. Treatment with E(2) only results in the most pronounced effect on
      gene expression (up to 1493 genes differentially expressed), proliferation and
      apoptosis. Tibolone, potentially metabolized to both estrogenic and progestagenic
      metabolites, shows some resemblance to E(2) signalling in the endometrium and, in
      contrast, shows significant resemblance to E(2) + MPA signalling in the
      myometrium. In the vagina the situation is entirely different; all three hormonal
      treatments result in regulation of a small number (4-73) of genes, in comparison
      to signalling in endometrium and myometrium. CONCLUSION: Endometrium and
      myometrium differentially respond to the hormone therapies and use completely
      different sets of genes to regulate similar biological processes, while in this
      experiment the upper part of the vagina is hardly hormone responsive.

PMID- 18077317
TI  - Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women.
AB  - BACKGROUND: Obesity is increasing rapidly among women all over the world. Obesity
      is a known risk factor for subfertility due to anovulation, but it is unknown
      whether obesity also affects spontaneous pregnancy chances in subfertile,
      ovulatory women. METHODS: We evaluated whether obesity affected the chance of a
      spontaneous pregnancy in a prospectively assembled cohort of 3029 consecutive
      subfertile couples. Women had to be ovulatory and had to have at least one patent
      tube, whereas men had to have a normal semen analysis. Time to spontaneous
      ongoing pregnancy within 12 months was the primary endpoint. RESULTS: The
      probability of a spontaneous pregnancy declined linearly with a body mass index
      (BMI) over 29 kg/m(2). Corrected for possible related factors, women with a high
      BMI had a 4% lower pregnancy rate per kg/m(2) increase [hazard ratio: 0.96 (95%
      CI 0.91-0.99)]. CONCLUSIONS: These results indicate that obesity is associated
      with lower pregnancy rates in subfertile ovulatory women.

PMID- 18077318
TI  - Differences in the endometrial transcript profile during the receptive period
      between women who were refractory to implantation and those who achieved
      pregnancy.
AB  - BACKGROUND: Gene expression profiling of normal receptive endometrium has been
      characterized, but intrinsic defects in endometrial gene expression associated
      with implantation failure have not been reported. METHODS: Women who had
      previously participated as recipients in oocyte donation cycles and repeatedly
      exhibited implantation failure (Group A, study group) or had at least one
      successful cycle (Group B, control group) and spontaneously fertile women (Group
      C, normal fertility group) were recruited. All were treated with exogenous
      estradiol and progesterone to induce an endometrial cycle, and an endometrial
      biopsy was taken on the seventh day of progesterone administration. RNA from each
      sample was analysed by cDNA microarrays to identify differentially expressed
      genes between groups. RESULTS: 63 transcripts were differentially expressed
      (>or=2-fold) between Groups A and B, of which 16 were subjected to real time RT
      PCR. Eleven of these were significantly decreased in Group A with regard to
      Groups B and C. Among the dysregulated genes were MMP-7, CXCR4, PAEP and C4BPA.
      CONCLUSIONS: Repeated implantation failure in some oocyte recipients is
      associated with an intrinsic defect in the expression of multiple genes in their
      endometrium. Significantly decreased levels of several transcripts in endometria
      without manifest abnormalities is demonstrated for the first time and shown to be
      associated with implantation failure.

PMID- 18077320
TI  - Developmental processes underlying the evolution of a derived foot morphology in
      salamanders.
AB  - Interdigital webbing has evolved repeatedly in tropical salamanders
      (bolitoglossines). This derived foot morphology is only one of many homoplastic
      traits in this diverse amphibian clade. Indeed, few if any morphological traits
      sort lineages within this clade. We investigate the processes underlying the
      homoplastic evolution of morphological characters in these salamanders by
      analyzing selective and developmental processes that generate interdigital
      webbing. We show that a pedomorphic developmental change generates the new foot
      morphology and that pedomorphosis affects a number of morphological traits, thus
      creating a developmental correlation among them. This correlation among traits is
      maintained across most species, thus facilitating the repeated evolution of
      traits. Although we find evidence that the changes in foot morphology are
      adaptive in one species, the evolution of webbing in all other species does not
      carry an adaptive signature. The new foot morphology therefore evolves
      repeatedly, even in the apparent absence of a direct selective advantage.

PMID- 18077321
TI  - Intracellular complexes of the beta2 subunit of the nicotinic acetylcholine
      receptor in brain identified by proteomics.
AB  - Nicotine acetylcholine receptors (nAChRs) comprise a family of ligand-gated
      channels widely expressed in the mammalian brain. The beta2 subunit is an
      abundant protein subunit critically involved in the cognitive and behavioral
      properties of nicotine as well as in the mechanisms of nicotine addiction. In
      this work, we used matrix-assisted laser desorption ionization time-of-flight
      tandem mass spectrometry (MALDI-TOF-TOF MS/MS) to uncover protein interactions of
      the intracellular loop of the beta2 subunit and components of immunoprecipitated
      beta2-nAChR complexes from mouse brain. Using the beta2-knockout mouse to exclude
      nonspecific binding to the beta2 antibody, we identify 21 nAChR-interacting
      proteins (NIPs) expressed in brain. Western blot analysis confirmed the
      association between the beta2 subunit and candidate NIPs. Based on their
      functional profiles, the hypothesis is suggested that the identified NIPs can
      regulate the trafficking and signaling of the beta2-nAChR. Interactions of the
      beta2 subunit with NIPs such as G protein alpha, G protein-regulated inducer of
      neurite outgrowth 1, and G protein-activated K(+) channel 1 suggest a link
      between nAChRs and cellular G protein pathways. These findings reveal
      intracellular interactions of the beta2 subunit and may contribute to the
      understanding of the mechanisms of nAChR signaling and trafficking in neurons.

PMID- 18077322
TI  - Wnt signal from multiple tissues and lin-3/EGF signal from the gonad maintain
      vulval precursor cell competence in Caenorhabditis elegans.
AB  - The Caenorhabditis elegans vulva has been a valuable paradigm for defining
      components of signaling pathways and elucidating how signaling events are
      coordinated to generate a developmental pattern. Vulval precursor cells (VPCs)
      are induced to adopt vulval fates in the third larval stage by LIN-3, an EGF-like
      signal produced by the gonad. Competence to respond to the inductive signal
      requires that the VPCs do not fuse to the major hypodermal syncytium, hyp7. We
      found that two Wnt-encoding genes, cwn-1 and egl-20, play a major role in
      preventing fusion of VPCs with hyp7 in the second larval stage. By using tissue
      specific rescue of mig-14/Wntless, which is required for the production of Wnt
      ligands, we found that Wnt signal produced by multiple tissues, including neurons
      and muscles, promotes or maintains VPC competence before vulval induction. In
      addition, through laser ablation and genetic analysis, we provide evidence that
      LIN-3 signal from the gonad also plays a significant role in preventing VPCs from
      fusing with hyp7. We propose that Wnt signaling plays a permissive role in
      preventing VPCs from fusing with hyp7 and reevaluate the roles of Wnt and LIN
      3/EGF signaling in competence and induction.

PMID- 18077323
TI  - Pulmonary CXCR2 regulates VCAM-1 and antigen-induced recruitment of mast cell
      progenitors.
AB  - Chemokine receptors regulate the trafficking of leukocytes by mediating
      chemotaxis and by their influence on the expression and/or affinity of leukocyte
      integrins. Using blocking mAb, we showed that antigen-induced recruitment of mast
      cell progenitors (MCp) to the lung requires interaction of a4 integrins on the
      MCp with endothelial vascular cell adhesion molecule 1 (VCAM-1). In seeking a
      chemokine component, we found that CXCR2-deficient but not CCR3- or CCR5
      deficient sensitized and antigen-challenged mice have significantly fewer lung
      MCp 1 day after challenge and fewer tracheal intraepithelial MC 1 week after
      challenge, implying that recruited MCp provide the source for these mature MC.
      Unexpectedly, reconstitution of sensitized, sublethally irradiated +/+ and -/-
      mice with bone marrow cells of either genotype indicated that expression of CXCR2
      by the migrating MCp was not required. Instead, receptor function by resident
      lung cells was required because normal BM did not reconstitute MCp recruitment in
      irradiated CXCR2(-/-) mice. The reduced MCp influx into the lung of CXCR2(-/-)
      mice was accompanied by reduced induction of VCAM-1 transcripts and reduced
      endothelial surface expression. Thus, these studies demonstrate a role for a
      chemokine receptor in regulating endothelial VCAM-1 expression, MCp migration,
      and the level of intraepithelial MC in the lung of aerosolized, antigen
      challenged mice.

PMID- 18077324
TI  - Indicators of 21st century socioclimatic exposure.
AB  - Policies that attempt to curb greenhouse gas emissions, allocate emissions
      rights, or distribute compensation to those most damaged by climate change must
      explicitly incorporate the international heterogeneity of the climate change
      threat. To capture the distinct susceptibilities associated with lack of
      infrastructure, potential property loss, and gross human exposure, we develop an
      integration of climate change projections and poverty, wealth, and population
      metrics. Our analysis shows that most nations of the world are threatened by the
      interaction of regional climatic changes with one or more relevant socioeconomic
      factors. Nations that have the highest levels of poverty, wealth, and population
      face greater relative exposure in those dimensions. However, for each of those
      socioeconomic indicators, spatial heterogeneity in projected climate change
      determines the overall international pattern of socioclimatic exposure. Our
      synthesis provides a critical missing piece to the climate change debate and
      should facilitate the formulation of climate policies that account for
      international variations in the threat of climate change across a range of
      socioeconomic dimensions.

PMID- 18077325
TI  - Processing and classification of chemical data inspired by insect olfaction.
AB  - The chemical sense of insects has evolved to encode and classify odorants. Thus,
      the neural circuits in their olfactory system are likely to implement an
      efficient method for coding, processing, and classifying chemical information.
      Here, we describe a computational method to process molecular representations and
      classify molecules. The three-step approach mimics neurocomputational principles
      observed in olfactory systems. In the first step, the original stimulus space is
      sampled by "virtual receptors," which are chemotopically arranged by a self
      organizing map. In the second step, the signals from the virtual receptors are
      decorrelated via correlation-based lateral inhibition. Finally, in the third
      step, olfactory scent perception is modeled by a machine learning classifier. We
      found that signal decorrelation during the second stage significantly increases
      the accuracy of odorant classification. Moreover, our results suggest that the
      proposed signal transform is capable of dimensionality reduction and is more
      robust against overdetermined representations than principal component scores.
      Our olfaction-inspired method was successfully applied to predicting
      bioactivities of pharmaceutically active compounds with high accuracy. It
      represents a way to efficiently connect chemical structure with biological
      activity space.

PMID- 18077326
TI  - The tumor suppressor Fhit acts as a repressor of beta-catenin transcriptional
      activity.
AB  - The Fra3B locus on chromosome 3p14.2 targeting the fragile histidine triad (Fhit)
      gene represents one of the most common fragile sites of the human genome and is
      associated with early preneoplastic and malignant disorders in multiple human
      tumors. Fhit was classified as a tumor suppressor; however, the molecular
      mechanisms of its function are not well established. Here, we report that Fhit
      associates with the lymphoid enhancer-binding factor 1/T cell factor/beta-catenin
      complex by directly binding to beta-catenin, a major player in the canonical Wnt
      pathway that is deregulated in numerous forms of human cancer. In binding to the
      beta-catenin C-terminal domain, Fhit represses transcription of target genes such
      as cyclin D1, axin2, MMP-14, and survivin. Knockdown of Fhit reversed this
      effect, whereas this reversal was not detectable when beta-catenin was knocked
      down simultaneously. The Fhit enzymatic activity as a diadenosine-polyphosphate
      hydrolase is not required for the down-regulation of beta-catenin-mediated
      transcription as examined with an enzymatic inactive Fhit-H96N protein. ChIPs
      revealed recruitment of Fhit/beta-catenin complexes to target gene promoters. In
      soft agar assays Fhit and beta-catenin are involved in regulation of anchorage
      independent growth. These observations assign to the tumor suppressor Fhit an
      unexpected role in the regulation of beta-catenin-mediated gene transcription.

PMID- 18077327
TI  - Dual-color superresolution imaging of genetically expressed probes within
      individual adhesion complexes.
AB  - Accurate determination of the relative positions of proteins within localized
      regions of the cell is essential for understanding their biological function.
      Although fluorescent fusion proteins are targeted with molecular precision, the
      position of these genetically expressed reporters is usually known only to the
      resolution of conventional optics ( approximately 200 nm). Here, we report the
      use of two-color photoactivated localization microscopy (PALM) to determine the
      ultrastructural relationship between different proteins fused to spectrally
      distinct photoactivatable fluorescent proteins (PA-FPs). The nonperturbative
      incorporation of these endogenous tags facilitates an imaging resolution in
      whole, fixed cells of approximately 20-30 nm at acquisition times of 5-30 min. We
      apply the technique to image different pairs of proteins assembled in adhesion
      complexes, the central attachment points between the cytoskeleton and the
      substrate in migrating cells. For several pairs, we find that proteins that seem
      colocalized when viewed by conventional optics are resolved as distinct
      interlocking nano-aggregates when imaged via PALM. The simplicity, minimal
      invasiveness, resolution, and speed of the technique all suggest its potential to
      directly visualize molecular interactions within cellular structures at the
      nanometer scale.

PMID- 18077328
TI  - Mapping dynamic protein interactions in MAP kinase signaling using live-cell
      fluorescence fluctuation spectroscopy and imaging.
AB  - Fluorescence correlation spectroscopy (FCS), fluorescence cross-correlation
      spectroscopy (FCCS), and photon counting histograms (PCH) are fluctuation methods
      that emerged recently as potentially useful tools for obtaining parameters of
      molecular dynamics, interactions, and oligomerization in vivo. Here, we report
      the successful implementation of FCS, FCCS, and PCH in live yeast cells using
      fluorescent protein-tagged proteins expressed from their native chromosomal loci,
      examining cytosolic dynamics and interactions among components of the mitogen
      activated protein kinase (MAPK) cascade, a widely occurring signaling motif, in
      response to mating pheromone. FCS analysis detailed the diffusion characteristics
      and mobile concentrations of MAPK proteins. FCCS analysis using EGFP and mCherry
      tagged protein pairs observed the interactions of Ste7 (MAPK kinase) with the
      MAPKs, Fus3 or Kss1, and of the scaffold protein, Ste5, with Ste7 and Ste11 (MAPK
      kinase kinase) in the cytosol, providing in vivo constants of their binding
      equilibrium. The interaction of Ste5 with Fus3 in the cytosol was below the limit
      of detection, suggesting a weak interaction, if it exists, with K(d) >400-500 nM.
      Using PCH, we show that cytosolic Ste5 were mostly monomers. Artificial
      dimerization of Ste5, as confirmed by PCH, using a dimerizing tag, stimulated the
      interaction between Ste5 and Fus3. Native Ste5 was found to bind Fus3
      preferentially at the cortex in pheromone-treated cells, as detected by
      fluorescence resonance energy transfer (FRET). These results provide a
      quantitative spatial map of MAPK complexes in vivo and directly support the model
      that membrane association and regulation of the Ste5 scaffold are critical steps
      in MAPK activation.

PMID- 18077329
TI  - Diet-induced obesity in mice causes changes in immune responses and bone loss
      manifested by bacterial challenge.
AB  - Obesity has been suggested to be associated with an increased susceptibility to
      bacterial infection. However, few studies have examined the effect of obesity on
      the immune response to bacterial infections. In the present study, we
      investigated the effect of obesity on innate immune responses to Porphyromonas
      gingivalis infection, an infection strongly associated with periodontitis. Mice
      with diet-induced obesity (DIO) and lean control C57BL/6 mice were infected
      orally or systemically with P. gingivalis, and periodontal pathology and systemic
      immune responses were examined postinfection. After oral infection with P.
      gingivalis, mice with DIO had a significantly higher level of alveolar bone loss
      than the lean controls. Oral microbial sampling disclosed higher levels of P.
      gingivalis in mice with DIO vs. lean mice during and after infection.
      Furthermore, animals with DIO exposed to oral infection or systemic inoculation
      of live P. gingivalis developed a blunted inflammatory response with reduced
      expression of TNF-alpha, IL-6, and serum amyloid A (SAA) at all time points
      compared with lean mice. Finally, peritoneal macrophages harvested from mice with
      DIO and exposed to P. gingivalis exhibited reduced levels of proinflammatory
      cytokines compared with lean mice and when exposed to P. gingivalis LPS treatment
      had a significantly reduced recruitment of NF-kappaB to both TNF-alpha and IL-10
      promoters 30 min after exposure. These data indicate that obesity interferes with
      the ability of the immune system to appropriately respond to P. gingivalis
      infection and suggest that this immune dysregulation participates in the
      increased alveolar bone loss after bacterial infection observed in mice with DIO.

PMID- 18077330
TI  - Mechanisms for segregating T cell receptor and adhesion molecules during
      immunological synapse formation in Jurkat T cells.
AB  - T cells interacting with antigen-presenting cells (APCs) form an "immunological
      synapse" (IS), a bull's-eye pattern composed of a central supramolecular
      activation cluster enriched with T cell receptors (TCRs) surrounded by a ring of
      adhesion molecules (a peripheral supramolecular activation cluster). The
      mechanism responsible for segregating TCR and adhesion molecules remains poorly
      understood. Here, we show that immortalized Jurkat T cells interacting with a
      planar lipid bilayer (mimicking an APC) will form an IS, thereby providing an
      accessible model system for studying the cell biological processes underlying IS
      formation. We found that an actin-dependent process caused TCR and adhesion
      proteins to cluster at the cell periphery, but these molecules appeared to
      segregate from one another at the earliest stages of microdomain formation. The
      TCR and adhesion microdomains attached to actin and were carried centripetally by
      retrograde flow. However, only the TCR microdomains penetrated into the actin
      depleted cell center, whereas the adhesion microdomains appeared to be unstable
      without an underlying actin cytoskeleton. Our results reveal that TCR and
      adhesion molecules spatially partition from one another well before the formation
      of a mature IS and that differential actin interactions help to shape and
      maintain the final bull's-eye pattern of the IS.

PMID- 18077331
TI  - Hydrogen sulfide increases thermotolerance and lifespan in Caenorhabditis
      elegans.
AB  - Hydrogen sulfide (H(2)S) is naturally produced in animal cells. Exogenous H(2)S
      has been shown to effect physiological changes that improve the capacity of
      mammals to survive in otherwise lethal conditions. However, the mechanisms
      required for such alterations are unknown. We investigated the physiological
      response of Caenorhabditis elegans to H(2)S to elucidate the molecular mechanisms
      of H(2)S action. Here we show that nematodes exposed to H(2)S are apparently
      healthy and do not exhibit phenotypes consistent with metabolic inhibition.
      Instead, animals exposed to H(2)S are thermotolerant and long-lived. These
      phenotypes require SIR-2.1 activity but are genetically independent of the
      insulin signaling pathway, mitochondrial dysfunction, and caloric restriction.
      These studies suggest that SIR-2.1 activity may translate environmental change
      into physiological alterations that improve survival. It is interesting to
      consider the possibility that the mechanisms by which H(2)S increases
      thermotolerance and lifespan in nematodes are conserved and that studies using C.
      elegans may help explain the beneficial effects observed in mammals exposed to
      H(2)S.

PMID- 18077332
TI  - Positive selection at the protein network periphery: evaluation in terms of
      structural constraints and cellular context.
AB  - Because of recent advances in genotyping and sequencing, human genetic variation
      and adaptive evolution in the primate lineage have become major research foci.
      Here, we examine the relationship between genetic signatures of adaptive
      evolution and network topology. We find a striking tendency of proteins that have
      been under positive selection (as compared with the chimpanzee) to be located at
      the periphery of the interaction network. Our results are based on the analysis
      of two types of genome evolution, both in terms of intra- and interspecies
      variation. First, we looked at single-nucleotide polymorphisms and their fixed
      variants, single-nucleotide differences in the human genome relative to the
      chimpanzee. Second, we examine fixed structural variants, specifically large
      segmental duplications and their polymorphic precursors known as copy number
      variants. We propose two complementary mechanisms that lead to the observed
      trends. First, we can rationalize them in terms of constraints imposed by protein
      structure: We find that positively selected sites are preferentially located on
      the exposed surface of proteins. Because central network proteins (hubs) are
      likely to have a larger fraction of their surface involved in interactions, they
      tend to be constrained and under negative selection. Conversely, we show that the
      interaction network roughly maps to cellular organization, with the periphery of
      the network corresponding to the cellular periphery (i.e., extracellular space or
      cell membrane). This suggests that the observed positive selection at the network
      periphery may be due to an increase of adaptive events on the cellular periphery
      responding to changing environments.

PMID- 18077333
TI  - A chemical approach to unraveling the biological function of the
      glycosylphosphatidylinositol anchor.
AB  - The glycosylphosphatidylinositol (GPI) anchor is a C-terminal posttranslational
      modification found on many eukaryotic proteins that reside in the outer leaflet
      of the cell membrane. The complex and diverse structures of GPI anchors suggest a
      rich spectrum of biological functions, but few have been confirmed experimentally
      because of the lack of appropriate techniques that allow for structural
      perturbation in a cellular context. We previously synthesized a series of GPI
      anchor analogs with systematic deletions within the glycan core and coupled them
      to the GFP by a combination of expressed protein ligation and native chemical
      ligation [Paulick MG, Wise AR, Forstner MB, Groves JT, Bertozzi CR (2007) J Am
      Chem Soc 129:11543-11550]. Here we investigate the behavior of these GPI-protein
      analogs in living cells. These modified proteins integrated into the plasma
      membranes of a variety of mammalian cells and were internalized and directed to
      recycling endosomes similarly to GFP bearing a native GPI anchor. The GPI-protein
      analogs also diffused freely in cellular membranes. However, changes in the
      glycan structure significantly affected membrane mobility, with the loss of
      monosaccharide units correlating to decreased diffusion. Thus, this cellular
      system provides a platform for dissecting the contributions of various GPI anchor
      components to their biological function.

PMID- 18077334
TI  - A universal driver of macroevolutionary change in the size of marine
      phytoplankton over the Cenozoic.
AB  - The size structure of phytoplankton assemblages strongly influences energy
      transfer through the food web and carbon cycling in the ocean. We determined the
      macroevolutionary trajectory in the median size of dinoflagellate cysts to
      compare with the macroevolutionary size change in other plankton groups. We found
      the median size of the dinoflagellate cysts generally decreases through the
      Cenozoic. Diatoms exhibit an extremely similar pattern in their median size over
      time, even though species diversity of the two groups has opposing trends,
      indicating that the macroevolutionary size change is an active response to
      selection pressure rather than a passive response to changes in diversity. The
      changes in the median size of dinoflagellate cysts are highly correlated with
      both deep ocean temperatures and the thermal gradient between the surface and
      deep waters, indicating the magnitude and frequency of nutrient availability may
      have acted as a selective factor in the macroevolution of cell size in the
      plankton. Our results suggest that climate, because it affects stratification in
      the ocean, is a universal abiotic driver that has been responsible for
      macroevolutionary changes in the size structure of marine planktonic communities
      over the past 65 million years of Earth's history.

PMID- 18077335
TI  - Intrinsic single-domain switching in ferroelectric materials on a nearly ideal
      surface.
AB  - Ferroelectric domain nucleation and growth in multiferroic BiFeO(3) is studied on
      a single-domain level by using piezoresponse force spectroscopy. Variation of
      local electromechanical response with dc tip bias is used to determine the size
      of the domain formed below the conductive scanning probe tip. The domain
      parameters are calculated self-consistently from the decoupled Green function
      theory by using tip geometry determined from the domain wall profile. The
      critical parameters of the nucleating domain and the activation energy for
      nucleation are determined. The switching mechanism is modeled by using the phase
      field method, and comparison with experimental results shows that the nucleation
      biases are within a factor of approximately 2 of the intrinsic thermodynamic
      limit. The role of atomic-scale defects and long-range elastic fields on
      nucleation bias lowering is discussed. These measurements open a pathway for
      quantitative studies of the role of a single defect on kinetics and
      thermodynamics of first order bias-induced phase transitions and electrochemical
      reactions.

PMID- 18077336
TI  - Melanocortin-2 receptor accessory protein MRAP forms antiparallel homodimers.
AB  - The melanocortin-2 (MC2) receptor accessory protein (MRAP) is required for
      trafficking of the G protein-coupled MC2 receptor to the plasma membrane. The
      mechanism of action and structure of MRAP, which has a single transmembrane
      domain, are unknown. Here, we show that MRAP displays a previously
      uncharacterized topology. Epitopes on both the N- and C-terminal ends of MRAP
      were localized on the external face of CHO cells at comparable levels. Using
      antibodies raised against N- and C-terminal MRAP peptides, we demonstrated that
      both ends of endogenous MRAP face the outside in adrenal cells. Nearly half of
      MRAP was glycosylated at the single endogenous N-terminal glycosylation site, and
      over half was glycosylated when the natural glycosylation site was replaced by
      one in the C-terminal domain. A mutant MRAP with potential glycosylation sites on
      both sides of the membrane was singly but not doubly glycosylated, suggesting
      that MRAP is not monotopic. Coimmunoprecipitation of differentially tagged MRAPs
      established that MRAP is a dimer. By selectively immunoprecipitating cell surface
      MRAP in one or the other orientation, we showed that MRAP homodimers are
      antiparallel and form a stable complex with MC2 receptor. In the absence of MRAP,
      MC2 receptor was trapped in the endoplasmic reticulum, but with MRAP, the MC2
      receptor was glycosylated and localized on the plasma membrane, where it signaled
      in response to ACTH. MRAP acted specifically, because it did not increase surface
      expression of other melanocortin, beta2-adrenergic, or TSH-releasing hormone
      receptors. MRAP is the first eukaryotic membrane protein identified with an
      antiparallel homodimeric structure.

PMID- 18077337
TI  - The alpha10 nicotinic acetylcholine receptor subunit is required for normal
      synaptic function and integrity of the olivocochlear system.
AB  - Although homomeric channels assembled from the alpha9 nicotinic acetylcholine
      receptor (nAChR) subunit are functional in vitro, electrophysiological,
      anatomical, and molecular data suggest that native cholinergic olivocochlear
      function is mediated via heteromeric nAChRs composed of both alpha9 and alpha10
      subunits. To gain insight into alpha10 subunit function in vivo, we examined
      olivo cochlear innervation and function in alpha10 null-mutant mice.
      Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells
      revealed ACh-gated currents in alpha10(+/+) and alpha10(+/-) mice, with no
      detectable responses to ACh in alpha10(-/-) mice. In contrast, a proportion of
      alpha10(-/-) outer hair cells showed small ACh-evoked currents. In alpha10(-/-)
      mutant mice, olivocochlear fiber stimulation failed to suppress distortion
      products, suggesting that the residual alpha9 homomeric nAChRs expressed by outer
      hair cells are unable to transduce efferent signals in vivo. Finally, alpha10(-/
      ) mice exhibit both an abnormal olivocochlear morphology and innervation to outer
      hair cells and a highly disorganized efferent innervation to the inner hair cell
      region. Our results demonstrate that alpha9(-/-) and alpha10(-/-) mice have
      overlapping but nonidentical phenotypes. Moreover, alpha10 nAChR subunits are
      required for normal olivocochlear activity because alpha9 homomeric nAChRs do not
      support maintenance of normal olivocochlear innervation or function in alpha10(-/
      ) mutant mice.

PMID- 18077338
TI  - Structural elements of the cholesterol-dependent cytolysins that are responsible
      for their cholesterol-sensitive membrane interactions.
AB  - The pore-forming mechanism of the cholesterol-dependent cytolysins (CDCs)
      exhibits an absolute requirement for membrane cholesterol. The structural
      elements of the CDCs that mediate this interaction are not well understood. Three
      short hydrophobic loops (L1-L3) and a highly conserved undecapeptide sequence at
      the tip of domain 4 of the CDC structure are known to anchor the CDC to the
      membrane. It has been thought that the undecapeptide directly mediates the
      interaction of the CDCs with a cholesterol-rich cell surface. Herein we show that
      the L1-L3 loops, not the undecapeptide, are responsible for mediating the
      specific interaction of the CDCs with cholesterol-rich membranes. The membrane
      insertion of the undecapeptide was uncoupled from membrane binding by the
      covalent modification of the undecapeptide cysteine thiol. Modification of the
      cysteine prevented prepore to pore conversion, but did not affect membrane
      binding, thus demonstrating that undecapeptide membrane insertion follows that of
      the L1-L3 loops. These studies provide an example of a structural motif that
      specifically mediates the interaction of a bacterial toxin with a cholesterol
      rich membrane.

PMID- 18077339
TI  - Placental syncytins: Genetic disjunction between the fusogenic and
      immunosuppressive activity of retroviral envelope proteins.
AB  - We have previously demonstrated that the envelope proteins of a murine and
      primate retrovirus are immunosuppressive in vivo. This property was manifested by
      the ability of the proteins, when expressed by allogeneic tumor cells normally
      rejected by engrafted mice, to have the env-expressing cells escape (at least
      transiently) immune rejection. Here, we analyzed the immunosuppressive activity
      of the human and murine syncytins. These are envelope genes from endogenous
      retroviruses independently coopted by ancestral hosts, conserved in evolution,
      specifically expressed in the placenta, and with a cell-cell fusogenic activity
      likely contributing to placenta morphogenesis. We show that in both humans and
      mice, one of the two syncytins (human syncytin-2 and mouse syncytin-B) is
      immunosuppressive and, rather unexpectedly, the other (human syncytin-1 and mouse
      syncytin-A) is not (albeit able to induce cell-cell fusion). Delineation of the
      immunosuppressive domain by deletion analysis, combined with a comparison between
      immunosuppressive and nonimmunosuppressive sequences, allowed us to derive a
      mutation rule targeted to specific amino acids, resulting in selective switch
      from immunosuppressive to nonimmunosuppressive envelope proteins and vice versa.
      These results unravel a critical function of retroviral envelopes, not
      necessarily "individually" selected for in the retrovirus endogenization process,
      albeit "tandemly" conserved in evolution for the syncytin pairs in primates and
      Muridae. Selective inactivation of immunosuppression, under conditions not
      affecting fusogenicity, should be important for understanding the role of this
      function in placental physiology and maternofetal tolerance.

PMID- 18077340
TI  - Loss of polyadenylation protein tauCstF-64 causes spermatogenic defects and male
      infertility.
AB  - Polyadenylation, the process of eukaryotic mRNA 3' end formation, is essential
      for gene expression and cell viability. Polyadenylation of male germ cell mRNAs
      is unusual, exhibiting increased alternative polyadenylation, decreased AAUAAA
      polyadenylation signal use, and reduced downstream sequence element dependence.
      CstF-64, the RNA-binding component of the cleavage stimulation factor (CstF),
      interacts with pre-mRNAs at sequences downstream of the cleavage site. In
      mammalian testes, meiotic XY-body formation causes suppression of X-linked CstF
      64 expression during pachynema. Consequently, an autosomal paralog, tauCstF-64
      (gene name Cstf2t), is expressed during meiosis and subsequent haploid
      differentiation. Here we show that targeted disruption of Cstf2t in mice causes
      aberrant spermatogenesis, specifically disrupting meiotic and postmeiotic
      development, resulting in male infertility resembling
      oligoasthenoteratozoospermia. Furthermore, the Cstf2t mutant phenotype displays
      variable expressivity such that spermatozoa show a broad range of defects. The
      overall phenotype is consistent with a requirement for tauCstF-64 in
      spermatogenesis as indicated by the significant changes in expression of
      thousands of genes in testes of Cstf2t(-/-) mice as measured by microarray. Our
      results indicate that, although the infertility in Cstf2t(-/-) males is due to
      low sperm count, multiple genes controlling many aspects of germ-cell development
      depend on tauCstF-64 for their normal expression. Finally, these transgenic mice
      provide a model for the study of polyadenylation in an isolated in vivo system
      and highlight the role of a growing family of testis-expressed autosomal
      retroposed variants of X-linked genes.

PMID- 18077341
TI  - Sickle cell vasoocclusion and rescue in a microfluidic device.
AB  - The pathophysiology of sickle cell disease is complicated by the multiscale
      processes that link the molecular genotype to the organismal phenotype:
      hemoglobin polymerization occurring in milliseconds, microscopic cellular
      sickling in a few seconds or less [Eaton WA, Hofrichter J (1990) Adv Protein Chem
      40:63-279], and macroscopic vessel occlusion over a time scale of minutes, the
      last of which is necessary for a crisis [Bunn HF (1997) N Engl J Med 337:762
      769]. Using a minimal but robust artificial microfluidic environment, we show
      that it is possible to evoke, control, and inhibit the collective vasoocclusive
      or jamming event in sickle cell disease. We use a combination of geometric,
      physical, chemical, and biological means to quantify the phase space for the
      onset of a jamming event, as well as its dissolution, and find that oxygen
      dependent sickle hemoglobin polymerization and melting alone are sufficient to
      recreate jamming and rescue. We further show that a key source of the
      heterogeneity in occlusion arises from the slow collective jamming of a confined,
      flowing suspension of soft cells that change their morphology and rheology
      relatively quickly. Finally, we quantify and investigate the effects of small
      molecule inhibitors of polymerization and therapeutic red blood cell exchange on
      this dynamical process. Our experimental study integrates the dynamics of
      collective processes associated with occlusion at the molecular, polymer,
      cellular, and tissue level; lays the foundation for a quantitative understanding
      of the rate-limiting processes; and provides a potential tool for optimizing and
      individualizing treatment, and identifying new therapies.

PMID- 18077342
TI  - Rapid dental development in a Middle Paleolithic Belgian Neanderthal.
AB  - The evolution of life history (pace of growth and reproduction) was crucial to
      ancient hominin adaptations. The study of dental development facilitates
      assessment of growth and development in fossil hominins with greater precision
      than other skeletal analyses. During tooth formation, biological rhythms manifest
      in enamel and dentine, creating a permanent record of growth rate and duration.
      Quantification of these internal and external incremental features yields
      developmental benchmarks, including ages at crown completion, tooth eruption, and
      root completion. Molar eruption is correlated with other aspects of life history.
      Recent evidence for developmental differences between modern humans and
      Neanderthals remains ambiguous. By measuring tooth formation in the entire
      dentition of a juvenile Neanderthal from Scladina, Belgium, we show that most
      teeth formed over a shorter time than in modern humans and that dental initiation
      and eruption were relatively advanced. By registering manifestations of stress
      across the dentition, we are able to present a precise chronology of Neanderthal
      dental development that differs from modern humans. At 8 years of age at death,
      this juvenile displays a degree of development comparable with modern human
      children who are several years older. We suggest that age at death in juvenile
      Neanderthals should not be assessed by comparison with modern human standards,
      particularly those derived from populations of European origin. Moreover,
      evidence from the Scladina juvenile and other similarly aged hominins suggests
      that a prolonged childhood and slow life history are unique to Homo sapiens.

PMID- 18077343
TI  - Hemopressin is an inverse agonist of CB1 cannabinoid receptors.
AB  - To date, the endogenous ligands described for cannabinoid receptors have been
      derived from membrane lipids. To identify a peptide ligand for CB(1) cannabinoid
      receptors, we used the recently described conformation-state sensitive antibodies
      and screened a panel of endogenous peptides from rodent brain or adipose tissue.
      This led to the identification of hemopressin (PVNFKFLSH) as a peptide ligand
      that selectively binds CB(1) cannabinoid receptors. We find that hemopressin is a
      CB(1) receptor-selective antagonist, because it is able to efficiently block
      signaling by CB(1) receptors but not by other members of family A G protein
      coupled receptors (including the closely related CB(2) receptors). Hemopressin
      also behaves as an inverse agonist of CB(1) receptors, because it is able to
      block the constitutive activity of these receptors to the same extent as its well
      characterized antagonist, rimonabant. Finally, we examine the activity of
      hemopressin in vivo using different models of pain and find that it exhibits
      antinociceptive effects when administered by either intrathecal, intraplantar, or
      oral routes, underscoring hemopressin's therapeutic potential. These results
      represent a demonstration of a peptide ligand for CB(1) cannabinoid receptors
      that also exhibits analgesic properties. These findings are likely to have a
      profound impact on the development of novel therapeutics targeting CB(1)
      receptors.

PMID- 18077344
TI  - Deficient ryanodine receptor S-nitrosylation increases sarcoplasmic reticulum
      calcium leak and arrhythmogenesis in cardiomyocytes.
AB  - Altered Ca(2+) homeostasis is a salient feature of heart disease, where the
      calcium release channel ryanodine receptor (RyR) plays a major role. Accumulating
      data support the notion that neuronal nitric oxide synthase (NOS1) regulates the
      cardiac RyR via S-nitrosylation. We tested the hypothesis that NOS1 deficiency
      impairs RyR S-nitrosylation, leading to altered Ca(2+) homeostasis. Diastolic
      Ca(2+) levels are elevated in NOS1(-/-) and NOS1/NOS3(-/-) but not NOS3(-/-)
      myocytes compared with wild-type (WT), suggesting diastolic Ca(2+) leakage.
      Measured leak was increased in NOS1(-/-) and NOS1/NOS3(-/-) but not in NOS3(-/-)
      myocytes compared with WT. Importantly, NOS1(-/-) and NOS1/NOS3(-/-) myocytes
      also exhibited spontaneous calcium waves. Whereas the stoichiometry and binding
      of FK-binding protein 12.6 to RyR and the degree of RyR phosphorylation were not
      altered in NOS1(-/-) hearts, RyR2 S-nitrosylation was substantially decreased,
      and the level of thiol oxidation increased. Together, these findings demonstrate
      that NOS1 deficiency causes RyR2 hyponitrosylation, leading to diastolic Ca(2+)
      leak and a proarrhythmic phenotype. NOS1 dysregulation may be a proximate cause
      of key phenotypes associated with heart disease.

PMID- 18077345
TI  - Fat and expanded act in parallel to regulate growth through warts.
AB  - The conserved Drosophila tumor suppressors Fat and Expanded have both recently
      been implicated in regulating the activity of the Warts tumor suppressor.
      However, there has been disagreement as to the nature of the links among Fat,
      Expanded, and Warts and the significance of these links to growth control. We
      report here that mutations in either expanded or fat can be rescued to viability
      simply by overexpressing Warts, indicating that their essential function is their
      influence on Warts rather than reported effects on endocytosis or other pathways.
      These rescue experiments also separate the transcriptional from the planar cell
      polarity branches of Fat signaling and reveal that Expanded does not directly
      affect polarity. We also investigate the relationship between expanded and fat
      and show, contrary to prior reports, that they have additive effects on imaginal
      disk growth and development. Although mutation of fat can cause partial loss of
      Expanded protein from the membrane, mutation of fat promotes growth even when
      Expanded is overexpressed and accumulates at its normal subapical location. These
      observations argue against recent proposals that Fat acts simply as a receptor
      for the Hippo signaling pathway and instead support the proposal that Fat and
      Expanded can act in parallel to regulate Warts through distinct mechanisms.

PMID- 18077346
TI  - Functional analysis of AHK1/ATHK1 and cytokinin receptor histidine kinases in
      response to abscisic acid, drought, and salt stress in Arabidopsis.
AB  - In plants, multistep component systems play important roles in signal
      transduction in response to environmental stimuli and plant growth regulators.
      Arabidopsis contains six nonethylene receptor histidine kinases, and, among them,
      AHK1/ATHK1, AHK2, AHK3, and CRE1 were shown to be stress-responsive, suggesting
      their roles in the regulation of plant response to abiotic stress. Gain- and loss
      of-function studies in Arabidopsis indicated that AHK1 is a positive regulator of
      drought and salt stress responses and abscisic acid (ABA) signaling. Microarray
      analysis of the ahk1 mutant revealed a down-regulation of many stress- and/or ABA
      inducible genes, including AREB1, ANAC, and DREB2A transcription factors and
      their downstream genes. These data suggest that AHK1 functions upstream of AREB1,
      ANAC, and DREB2A and positively controls stress responses through both ABA
      dependent and ABA-independent signaling pathways. In addition, AHK1 plays
      important roles in plant growth because the ahk1 ahk2 ahk3 triple mutant showed
      further reduced growth. Unlike AHK1, loss-of-function analysis of ahk2, ahk3, and
      cre1 implied that the stress-responsive AHK2, AHK3, and CRE1 act as negative
      regulators in ABA signaling. AHK2 and AHK3 also negatively control osmotic stress
      responses in Arabidopsis because ahk2, ahk3, and ahk2 ahk3 mutants were strongly
      tolerant to drought and salt stress due to up-regulation of many stress- and/or
      ABA-inducible genes. Last, cytokinin clearly mediates stress responses because it
      was required for CRE1 to function as a negative regulator of osmotic stress.

PMID- 18077347
TI  - Characterization and engineering of the bifunctional N- and O-glucosyltransferase
      involved in xenobiotic metabolism in plants.
AB  - The glucosylation of pollutant and pesticide metabolites in plants controls their
      bioactivity and the formation of subsequent chemical residues. The model plant
      Arabidopsis thaliana contains >100 glycosyltransferases (GTs) dedicated to small
      molecule conjugation and, whereas 44 of these enzymes catalyze the O
      glucosylation of chlorinated phenols, only one, UGT72B1, shows appreciable N
      glucosylating activity toward chloroanilines. UGT72B1 is a bifunctional O
      glucosyltransferase (OGT) and N-glucosyltransferase (NGT). To investigate this
      unique dual activity, the structure of the protein was solved, at resolutions up
      to 1.45 A, in various forms including the Michaelis complex with intact donor
      analog and trichlorophenol acceptor. The catalytic mechanism and basis for O/N
      specificity was probed by mutagenesis and domain shuffling with an orthologous
      enzyme from Brassica napus (BnUGT), which possesses only OGT activity. Mutation
      of BnUGT at just two positions (D312N and F315Y) installed high levels of NGT
      activity. Molecular modeling revealed the connectivity of these residues to H19
      on UGT72B1, with its mutagenesis exclusively defining NGT activity in the
      Arabidopsis enzyme. These results shed light on the conjugation of nonnatural
      substrates by plant GTs, highlighting the catalytic plasticity of this enzyme
      class and the ability to engineer unusual and desirable transfer to nitrogen
      based acceptors.

PMID- 18077348
TI  - Reconstruction of ancestral protein interaction networks for the bZIP
      transcription factors.
AB  - As whole-genome protein-protein interaction datasets become available for a wide
      range of species, evolutionary biologists have the opportunity to address some of
      the unanswered questions surrounding the evolution of these complex systems.
      Protein interaction networks from divergent organisms may be compared to
      investigate how gene duplication, deletion, and rewiring processes have shaped
      the evolution of their contemporary structures. However, current approaches for
      comparing observed networks from multiple species lack the phylogenetic context
      necessary to reconstruct the evolutionary history of a network. Here we show how
      probabilistic modeling can provide a platform for the quantitative analysis of
      multiple protein interaction networks. We apply this technique to the
      reconstruction of ancestral networks for the bZIP family of transcription factors
      and find that excellent agreement is obtained with an alternative sequence-based
      method for the prediction of leucine zipper interactions. Further analysis shows
      our probabilistic method to be significantly more robust to the presence of noise
      in the observed network data than a simple parsimony-based approach. In addition,
      the integration of evidence over multiple species means that the same method may
      be used to improve the quality of noisy interaction data for extant species. The
      ancestral states of a protein interaction network have been reconstructed here by
      using an explicit probabilistic model of network evolution. We anticipate that
      this model will form the basis of more general methods for probing the
      evolutionary history of biochemical networks.

PMID- 18077349
TI  - Mutations of HNF-1beta inhibit epithelial morphogenesis through dysregulation of
      SOCS-3.
AB  - Hepatocyte nuclear factor-1beta (HNF-1beta) is a Pit-1, Oct-1/2, Unc-86 (POU)
      homeodomain-containing transcription factor expressed in the kidney, liver,
      pancreas, and other epithelial organs. Mutations of HNF-1beta cause maturity
      onset diabetes of the young, type 5 (MODY5), which is characterized by early
      onset diabetes mellitus and congenital malformations of the kidney, pancreas, and
      genital tract. Knockout of HNF-1beta in the mouse kidney results in cyst
      formation. However, the signaling pathways and transcriptional programs
      controlled by HNF-1beta are poorly understood. Using genome-wide chromatin
      immunoprecipitation and DNA microarray (ChIP-chip) and microarray analysis of
      mRNA expression, we identified SOCS3 (suppressor of cytokine signaling-3) as a
      previously unrecognized target gene of HNF-1beta in the kidney. HNF-1beta binds
      to the SOCS3 promoter and represses SOCS3 transcription. The expression of SOCS3
      is increased in HNF-1beta knockout mice and in renal epithelial cells expressing
      dominant-negative mutant HNF-1beta. Increased levels of SOCS-3 inhibit HGF
      induced tubulogenesis by decreasing phosphorylation of Erk and STAT-3.
      Conversely, knockdown of SOCS-3 in renal epithelial cells expressing dominant
      negative mutant HNF-1beta rescues the defect in HGF-induced tubulogenesis by
      restoring phosphorylation of Erk and STAT-3. Thus, HNF-1beta regulates
      tubulogenesis by controlling the levels of SOCS-3 expression. Manipulating the
      levels of SOCS-3 may be a useful therapeutic approach for human diseases induced
      by HNF-1beta mutations.

PMID- 18077350
TI  - Revealing the multiple structures of serine.
AB  - We explored the conformational landscape of the proteinogenic amino acid serine
      [CH(2)OH CH(NH(2)) COOH] in the gas phase. Solid serine was vaporized by laser
      ablation, expanded in a supersonic jet, and characterized by Fourier transform
      microwave spectroscopy. In the isolation conditions of the jet there have been
      discovered up to seven different neutral (non-zwitterionic) structures of serine,
      which are conclusively identified by the comparison between the experimental
      values of the rotational and quadrupole coupling constants with those predicted
      by ab initio calculations. These seven forms can serve as a basis to represent
      the shape of serine in the gas phase. From the postexpansion abundances we
      derived the conformational stability trend, which is controlled by the subtle
      network of intramolecular hydrogen bonds formed between the polar groups in the
      amino acid backbone and the hydroxy side chain. It is proposed that
      conformational cooling perturbs the equilibrium conformational distribution;
      thus, some of the lower-energy forms are "missing" in the supersonic expansion.

PMID- 18077351
TI  - The role of Pleistocene refugia and rivers in shaping gorilla genetic diversity
      in central Africa.
AB  - The role of Pleistocene forest refugia and rivers in the evolutionary
      diversification of tropical biota has been the subject of considerable debate. A
      range-wide analysis of gorilla mitochondrial and nuclear variation was used to
      test the potential role of both refugia and rivers in shaping genetic diversity
      in current populations. Results reveal strong patterns of regional
      differentiation that are consistent with refugial hypotheses for central Africa.
      Four major mitochondrial haplogroups are evident with the greatest divergence
      between eastern (A, B) and western (C, D) gorillas. Coalescent simulations reject
      a model of recent east-west separation during the last glacial maximum but are
      consistent with a divergence time within the Pleistocene. Microsatellite data
      also support a similar regional pattern of population genetic structure.
      Signatures of demographic expansion were detected in eastern lowland (B) and
      Gabon/Congo (D3) mitochondrial haplogroups and are consistent with a history of
      postglacial expansion from formerly isolated refugia. Although most mitochondrial
      haplogroups are regionally defined, limited admixture is evident between
      neighboring haplogroups. Mantel tests reveal a significant isolation-by-distance
      effect among western lowland gorilla populations. However, mitochondrial genetic
      distances also correlate with the distance required to circumnavigate intervening
      rivers, indicating a possible role for rivers in partitioning gorilla genetic
      diversity. Comparative data are needed to evaluate the importance of both
      mechanisms of vicariance in other African rainforest taxa.

PMID- 18077352
TI  - Refinement of the x-ray structure of the RC LH1 core complex from
      Rhodopseudomonas palustris by single-molecule spectroscopy.
AB  - A unique combination of single-molecule spectroscopy with numerical simulations
      has allowed us to achieve a refined structural model for the bacteriochlorophyll
      a (BChl a) pigment arrangement in reaction center-light-harvesting 1 core
      complexes of Rhodopseudomonas palustris. Details in the optical spectra, such as
      spectral separation and mutual polarizations of spectral bands, are compared with
      results from numerical simulations for various models of the BChl a arrangement
      that were all well within the 4.8-A limit of the accuracy of the available x-ray
      structure. The experimental data are consistent with a geometry where 15 BChl a
      dimers, each taken homologous to those from light-harvesting 2 complex from
      Rhodopseudomonas acidophila, are arranged in an overall elliptical structure
      featuring a gap on the long side of the ellipse.

PMID- 18077353
TI  - FoxO transcription factors activate Akt and attenuate insulin signaling in heart
      by inhibiting protein phosphatases.
AB  - Insulin resistance and metabolic syndrome are rapidly expanding public health
      problems. Acting through the PI3K/Akt pathway, insulin and insulin-like growth
      factor-1 (IGF-1) inactivate FoxO transcription factors, a class of highly
      conserved proteins important in numerous physiological functions. However, even
      as FoxO is a downstream target of insulin, FoxO factors also control upstream
      signaling elements governing insulin sensitivity and glucose metabolism. Here, we
      report that sustained activation of either FoxO1 or FoxO3 in cardiac myocytes
      increases basal levels of Akt phosphorylation and kinase activity. FoxO-activated
      Akt directly interacts with and phosphorylates FoxO, providing feedback
      inhibition. We reported previously that FoxO factors attenuate cardiomyocyte
      calcineurin (PP2B) activity. We now show that calcineurin forms a complex with
      Akt and inhibition of calcineurin enhances Akt phosphorylation. In addition, FoxO
      activity suppresses protein phosphatase 2A (PP2A) and disrupts Akt-PP2A and Akt
      calcineurin interactions. Repression of Akt-PP2A/B interactions and phosphatase
      activities contributes, at least in part, to FoxO-dependent increases in Akt
      phosphorylation and kinase activity. Resveratrol, an activator of Sirt1,
      increases the transcriptional activity of FoxO1 and triggers Akt phosphorylation
      in heart. Importantly, FoxO-mediated increases in Akt activity diminish insulin
      signaling, as manifested by reduced Akt phosphorylation, reduced membrane
      translocation of Glut4, and decreased insulin-triggered glucose uptake. Also,
      inactivation of the gene coding for FoxO3 enhances insulin-dependent Akt
      phosphorylation. Taken together, this study demonstrates that changes in FoxO
      activity have a dose-responsive repressive effect on insulin signaling in
      cardiomyocytes through inhibition of protein phosphatases, which leads to altered
      Akt activation, reduced insulin sensitivity, and impaired glucose metabolism.

PMID- 18077354
TI  - Small RNAs making a small protein.

PMID- 18077355
TI  - Repopulation of adult and neonatal mice with human hepatocytes: a chimeric animal
      model.
AB  - We report the successful transplantation of human hepatocytes in immunodeficient,
      fumarylacetoacetate hydrolase-deficient (fah(-/-)) mice. Engraftment occurs over
      the entire liver acinus upon transplantation. A few weeks after transplantation,
      increasing concentrations of human proteins (e.g., human albumin and human C3a)
      can be measured in the blood of the recipient mouse. No fusion between mouse and
      human hepatocytes can be detected. Three months after transplantation, up to 20%
      of the mouse liver is repopulated by human hepatocytes, and sustained expression
      of lentiviral vector transduced gene can be observed. We further report the
      development of a hepatocyte transplantation method involving a transcutaneous,
      intrahepatic injection in neonatal mice. Human hepatocytes engraft over the
      entire injected lobe with an expansion pattern similar to those observed with
      intrasplenic transplantation.

PMID- 18077356
TI  - Sequence of late molecular events in the activation of rhodopsin.
AB  - Activation of the G protein-coupled receptor rhodopsin involves both the motion
      of transmembrane helix 6 (TM6) and proton exchange events. To study how these
      activation steps relate to each other, spin-labeled rhodopsin in solutions of
      dodecyl maltoside was used so that time-resolved TM6 motion and proton exchange
      could each be monitored as a function of pH and temperature after an activating
      light flash. The results reveal that the motion of TM6 is not synchronized with
      deprotonation of the Schiff base that binds the chromophore to the protein but is
      an order of magnitude slower at 30 degrees C. However, TM6 motion and the uptake
      of a proton from solution in the neutral pH range follow the same time course.
      Importantly, the motion of TM6 is virtually independent of pH, as is Schiff base
      deprotonation under the conditions used, whereas proton uptake titrates with a pK
      of 6.5. This finding shows that proton uptake is a consequence rather than a
      cause of helix motion. Activated rhodopsin binds to and subsequently activates
      the cognate G protein, transducin. It has been shown that peptides derived from
      the C terminus of the transducin alpha-subunit mimic in part binding of the
      intact G protein. These peptides are found to bind to rhodopsin after TM6
      movement, resulting in the release of protons. Collectively, the data suggest the
      following temporal sequence of events involved in activation: (i) internal Schiff
      base proton transfer; (ii) TM6 movement; and (iii) proton uptake from solution
      and binding of transducin.

PMID- 18077357
TI  - Notch regulates cell fate and dendrite morphology of newborn neurons in the
      postnatal dentate gyrus.
AB  - The lifelong addition of neurons to the hippocampus is a remarkable form of
      structural plasticity, yet the molecular controls over proliferation, neuronal
      fate determination, survival, and maturation are poorly understood. Expression of
      Notch1 was found to change dynamically depending on the differentiation state of
      neural precursor cells. Through the use of inducible gain- and loss-of-function
      of Notch1 mice we show that this membrane receptor is essential to these distinct
      processes. We found in vivo that activated Notch1 overexpression induces
      proliferation, whereas gamma-secretase inhibition or genetic ablation of Notch1
      promotes cell cycle exit, indicating that the level of activated Notch1 regulates
      the magnitude of neurogenesis from postnatal progenitor cells. Abrogation of
      Notch signaling in vivo or in vitro leads to a transition from neural stem or
      precursor cells to transit-amplifying cells or neurons. Further, genetic Notch1
      manipulation modulates survival and dendritic morphology of newborn granule
      cells. These results provide evidence for the expansive prevalence of Notch
      signaling in hippocampal morphogenesis and plasticity, suggesting that Notch1
      could be a target of diverse traumatic and environmental modulators of adult
      neurogenesis.

PMID- 18077358
TI  - Modulation of human natural killer T cell ligands on TLR-mediated antigen
      presenting cell activation.
AB  - Invariant natural killer T (iNKT) cells are a subset of nonconventional T cells
      recognizing endogenous and/or exogenous glycolipid antigens in the context of
      CD1d molecules. It remains unclear whether innate stimuli can modify the profile
      of endogenous lipids recognized by iNKT cells on the surface of antigen
      presenting cells (APCs). We report that activation of human APCs by Toll-like
      receptor ligands (TLR-L) modulates the lipid biosynthetic pathway, resulting in
      enhanced recognition of CD1d-associated lipids by iNKT cells, as defined by IFN
      gamma secretion. APC-derived soluble factors further increase CD1d-restricted
      iNKT cell activation. Finally, using soluble tetrameric iNKT T cell receptors
      (TCR) as a staining reagent, we demonstrate specific up-regulation of CD1d-bound
      ligand(s) on TLR-mediated APC maturation. The ability of innate stimuli to
      modulate the lipid profile of APCs resulting in iNKT cell activation and APC
      maturation underscores the role of iNKT cells in assisting priming of antigen
      specific immune responses.

PMID- 18077359
TI  - A learning program that ensures prompt and versatile vocal imitation.
AB  - Here we show how a migratory songbird, the chipping sparrow (Spizella passerina),
      achieves prompt and precise vocal imitation. Juvenile chipping sparrow males
      develop five to seven potential precursor songs; the normal development of these
      songs requires intact hearing but not imitation from external models. The
      potential precursor songs conform with general species-typical song parameters
      but differ from the song of wild, adult territorial males. As chipping sparrow
      males return from migration to start their first breeding season, they settle
      close to an older adult. The young male then stops producing all but one of its
      precursor songs, retaining the one that most resembles that of its neighbor. This
      single song then becomes more variable and, in a matter of days, is altered to
      closely match the neighbor's song. This elegant solution ensures species
      specificity and promptness of imitation.

PMID- 18077360
TI  - Prion strain discrimination in cell culture: the cell panel assay.
AB  - Prions are thought to consist mainly or entirely of misfolded PrP, a
      constitutively expressed host protein. Prions associated with the same PrP
      sequence may occur in the form of different strains; the strain phenotype is
      believed to be encoded by the conformation of the PrP. Some cell lines can be
      persistently infected by prions and, interestingly, show preference for certain
      strains. We report that a cloned murine neuroblastoma cell population, N2a-PK1,
      is highly heterogeneous in regard to its susceptibility to RML and 22L prions.
      Remarkably, sibling subclones may show very different relative susceptibilities
      to the two strains, indicating that the responses can vary independently. We have
      assembled four cell lines, N2a-PK1, N2a-R33, LD9 and CAD5, which show widely
      different responses to prion strains RML, 22L, 301C, and Me7, into a panel that
      allows their discrimination in vitro within 2 weeks, using the standard scrapie
      cell assay (SSCA).

PMID- 18077361
TI  - Perceiving the avidity of T cell activation can be translated into peripheral T
      cell regulation.
AB  - The structure recognized by regulatory T cells that enables them to discriminate
      self from nonself in the periphery is one of the central issues of regulatory T
      cell biology. A link between immunoregulation and self-nonself discrimination has
      emerged from experiments showing that Qa-1-restricted CD8(+) T cells selectively
      down-regulate target T cells activated by the intermediate avidity of their own T
      cell antigen receptor-ligand interactions. Because the peripheral self-reactive T
      cell repertoire is devoid of high-avidity T cells compared with the foreign
      reactive repertoire, as a result of thymic negative selection, the selective down
      regulation of intermediate but not high-avidity T cells enables the immune system
      to suppress autoimmunity without damaging the ongoing immune response to foreign
      pathogens. However, the molecular mechanism delineating how avidity of T cell
      activation is perceived by the regulatory T cells has not been elucidated. Here
      we show that a heat shock peptide (Hsp60sp), coupled with the MHC class Ib
      molecule Qa-1, is a surrogate target structure that is preferentially expressed
      at a higher level on the intermediate avidity T cells and specifically recognized
      by the Qa-1-restricted CD8(+) T cells. The biological significance of this
      observation was confirmed by the ability of Hsp60sp-loaded relevant dendritic
      cells to induce a Qa-1-restricted CD8(+) T cell-mediated protection from
      autoimmune encephalopathy in the experimental allergic encephalomyelitis model.
      Thus, perceiving the avidity of T cell activation can be translated into
      peripheral T cell regulation to discriminate self from nonself in the periphery
      to maintain self-tolerance.

PMID- 18077363
TI  - A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.
AB  - Protein kinases play a pivotal role in cell signaling, and dysregulation of many
      kinases has been linked to disease development. A large number of kinase
      inhibitors are therefore currently under investigation in clinical trials, and so
      far seven inhibitors have been approved as anti-cancer drugs. In addition, kinase
      inhibitors are widely used as specific probes to study cell signaling, but
      systematic studies describing selectivity of these reagents across a panel of
      diverse kinases are largely lacking. Here we evaluated the specificity of 156
      validated kinase inhibitors, including inhibitors used in clinical trials,
      against 60 human Ser/Thr kinases using a thermal stability shift assay. Our
      analysis revealed many unexpected cross-reactivities for inhibitors thought to be
      specific for certain targets. We also found that certain combinations of active
      site residues in the ATP-binding site correlated with the detected ligand
      promiscuity and that some kinases are highly sensitive to inhibition using
      diverse chemotypes, suggesting them as preferred intervention points. Our results
      uncovered also inhibitor cross-reactivities that may lead to alternate clinical
      applications. For example, LY333'531, a PKCbeta inhibitor currently in phase III
      clinical trials, efficiently inhibited PIM1 kinase in our screen, a suggested
      target for treatment of leukemia. We determined the binding mode of this
      inhibitor by x-ray crystallography and in addition showed that LY333'531 induced
      cell death and significantly suppressed growth of leukemic cells from acute
      myeloid leukemia patients.

PMID- 18077364
TI  - Highly permeable polymeric membranes based on the incorporation of the functional
      water channel protein Aquaporin Z.
AB  - The permeability and solute transport characteristics of amphiphilic triblock
      polymer vesicles containing the bacterial water-channel protein Aquaporin Z
      (AqpZ) were investigated. The vesicles were made of a block copolymer with
      symmetric poly-(2-methyloxazoline)-poly-(dimethylsiloxane)-poly-(2
      methyloxazoline) (PMOXA(15)-PDMS(110)-PMOXA(15)) repeat units. Light-scattering
      measurements on pure polymer vesicles subject to an outwardly directed salt
      gradient in a stopped-flow apparatus indicated that the polymer vesicles were
      highly impermeable. However, a large enhancement in water productivity
      (permeability per unit driving force) of up to approximately 800 times that of
      pure polymer was observed when AqpZ was incorporated. The activation energy
      (E(a)) of water transport for the protein-polymer vesicles (3.4 kcal/mol)
      corresponded to that reported for water-channel-mediated water transport in lipid
      membranes. The solute reflection coefficients of glucose, glycerol, salt, and
      urea were also calculated, and indicated that these solutes are completely
      rejected. The productivity of AqpZ-incorporated polymer membranes was at least an
      order of magnitude larger than values for existing salt-rejecting polymeric
      membranes. The approach followed here may lead to more productive and sustainable
      water treatment membranes, whereas the variable levels of permeability obtained
      with different concentrations of AqpZ may provide a key property for drug
      delivery applications.

PMID- 18077365
TI  - Water-like solvation thermodynamics in a spherically symmetric solvent model with
      two characteristic lengths.
AB  - We examine by molecular dynamics simulation the solubility of small apolar
      solutes in a solvent whose particles interact via the Jagla potential, a
      spherically symmetric ramp potential with two characteristic lengths: an
      impenetrable hard core and a penetrable soft core. The Jagla fluid has been
      recently shown to possess water-like structural, dynamic, and thermodynamic
      anomalies. We find that the solubility exhibits a minimum with respect to
      temperature at fixed pressure and thereby show that the Jagla fluid also displays
      water-like solvation thermodynamics. We further find low-temperature swelling of
      a hard-sphere chain dissolved in the Jagla fluid and relate this phenomenon to
      cold unfolding of globular proteins. Our results are consistent with the
      possibility that the presence of two characteristic lengths in the Jagla
      potential is a key feature of water-like solvation thermodynamics. The penetrable
      core becomes increasingly important at low temperatures, which favors the
      formation of low-density, open structures in the Jagla solvent.

PMID- 18077366
TI  - Life history trade-offs explain the evolution of human pygmies.
AB  - Explanations for the evolution of human pygmies continue to be a matter of
      controversy, recently fuelled by the disagreements surrounding the interpretation
      of the fossil hominin Homo floresiensis. Traditional hypotheses assume that the
      small body size of human pygmies is an adaptation to special challenges, such as
      thermoregulation, locomotion in dense forests, or endurance against starvation.
      Here, we present an analysis of stature, growth, and individual fitness for a
      large population of Aeta and a smaller one of Batak from the Philippines and
      compare it with data on other pygmy groups accumulated by anthropologists for a
      century. The results challenge traditional explanations of human pygmy body size.
      We argue that human pygmy populations and adaptations evolved independently as
      the result of a life history tradeoff between the fertility benefits of larger
      body size against the costs of late growth cessation, under circumstances of
      significant young and adult mortality. Human pygmies do not appear to have
      evolved through positive selection for small stature-this was a by-product of
      selection for early onset of reproduction.

PMID- 18077367
TI  - A coactivator trap identifies NONO (p54nrb) as a component of the cAMP-signaling
      pathway.
AB  - Signal transduction pathways often use a transcriptional component to mediate
      adaptive cellular responses. Coactivator proteins function prominently in these
      pathways as the conduit to the basic transcriptional machinery. Here we present a
      high-throughput cell-based screening strategy, termed the "coactivator trap," to
      study the functional interactions of coactivators with transcription factors. We
      applied this strategy to the cAMP signaling pathway, which utilizes two families
      of coactivators, the cAMP response element binding protein (CREB) binding protein
      (CBP)/p300 family and the recently identified transducers of regulated CREB
      activity family (TORCs1-3). In addition to identifying numerous known
      interactions of these coactivators, this analysis identified NONO (p54(nrb)) as a
      TORC-interacting protein. RNA interference experiments demonstrate that NONO is
      necessary for cAMP-dependent activation of CREB target genes in vivo.
      Furthermore, TORC2 and NONO complex on cAMP-responsive promoters, and NONO acts
      as a bridge between the CREB/TORC complex and RNA polymerase II. These data
      demonstrate the utility of the coactivator trap by identification of a component
      of cAMP-mediated transcription.

PMID- 18077362
TI  - Molecular identification of bacteria in bronchoalveolar lavage fluid from
      children with cystic fibrosis.
AB  - Culture of bronchoalveolar lavage fluid (BALF) is the gold standard for detection
      of pathogens in the lower airways in cystic fibrosis (CF). However, current
      culture results do not explain all clinical observations in CF, including
      negative culture results during pulmonary exacerbation and inflammation in the
      absence of pathogens. We hypothesize that organisms not routinely identified by
      culture occur in the CF airway and may contribute to disease. To test this
      hypothesis we used a culture-independent molecular approach, based on use of rRNA
      sequence analysis, to assess the bacterial composition of BALF from children with
      CF and disease controls (DC). Specimens from 42 subjects (28 CF) were examined,
      and approximately 6,600 total clones were screened to identify 121 species of
      bacteria. In general, a single rRNA type dominated clone libraries from CF
      specimens, but not DC. Thirteen CF subjects contained bacteria that are not
      routinely assessed by culture. In four CF subjects, candidate pathogens were
      identified and include the anaerobe Prevotella denticola, a Lysobacter sp., and
      members of the Rickettsiales. The presumptive pathogens Tropheryma whipplei and
      Granulicatella elegans were identified in cases from the DC group. The presence
      of unexpected bacteria in CF may explain inflammation without documented
      pathogens and consequent failure to respond to standard treatment. These results
      show that molecular techniques provide a broader perspective on airway bacteria
      than do routine clinical cultures and thus can identify targets for further
      clinical evaluation.

PMID- 18077368
TI  - Deletion of the BH3-only protein puma protects motoneurons from ER stress-induced
      apoptosis and delays motoneuron loss in ALS mice.
AB  - BH3-only proteins couple diverse stress signals to the evolutionarily conserved
      mitochondrial apoptosis pathway. Previously, we reported that the activation of
      the BH3-only protein p53-up-regulated mediator of apoptosis (Puma) was necessary
      and sufficient for endoplasmic reticulum (ER) stress- and proteasome inhibition
      induced apoptosis in neuroblastoma and other cancer cells. Defects in protein
      quality control have also been suggested to be a key event in ALS, a fatal
      neurodegenerative condition characterized by motoneuron degeneration. Using the
      SOD1(G93A) mouse model as well as human post mortem samples from ALS patients, we
      show evidence for increased ER stress and defects in protein degradation in
      motoneurons during disease progression. Before symptom onset, we detected a
      significant up-regulation of Puma in motoneurons of SOD1(G93A) mice. Genetic
      deletion of puma significantly improved motoneuron survival and delayed disease
      onset and motor dysfunction in SOD1(G93A) mice. However, it had no significant
      effect on lifespan, suggesting that other ER stress-related cell-death proteins
      or other factors, such as excitotoxicity, necrosis, or inflammatory injury, may
      contribute at later disease stages. Indeed, further experiments using cultured
      motoneurons revealed that genetic deletion of puma protected motoneurons against
      ER stress-induced apoptosis but showed no effect against excitotoxic injury.
      These findings demonstrate that a single BH3-only protein, the ER stress
      associated protein Puma, plays an important role during the early stages of
      chronic neurodegeneration in vivo.

PMID- 18077369
TI  - Single-vesicle imaging reveals that synaptic vesicle exocytosis and endocytosis
      are coupled by a single stochastic mode.
AB  - The nature of synaptic vesicle recycling at nerve terminals has been a subject of
      considerable debate for >35 years. Here, we report the use of an optical strategy
      that allows the exocytosis and retrieval of synaptic components to be tracked in
      real time at single-molecule sensitivity in living nerve terminals. This approach
      has allowed us to examine the recycling of synaptic vesicles in response to
      single action potentials. Our results show that, after exocytosis, individual
      synaptic vesicles are retrieved by a stochastic process with an exponential
      distribution of delay times, with a mean time of approximately 14 s. We propose
      that evidence for fast endocytosis, such as that proposed to support the presence
      of kiss-and-run, is likely explained by the stochastic nature of a slower
      process.

PMID- 18077370
TI  - The Na+/I symporter (NIS) mediates electroneutral active transport of the
      environmental pollutant perchlorate.
AB  - The Na(+)/I(-) symporter (NIS) is a key plasma membrane protein that mediates
      active I(-) uptake in the thyroid, lactating breast, and other tissues with an
      electrogenic stoichiometry of 2 Na(+) per I(-). In the thyroid, NIS-mediated I(-)
      uptake is the first step in the biosynthesis of the iodine-containing thyroid
      hormones, which are essential early in life for proper CNS development. In the
      lactating breast, NIS mediates the translocation of I(-) to the milk, thus
      supplying this essential anion to the nursing newborn. Perchlorate (ClO(4)(-)) is
      a well known competitive inhibitor of NIS. Exposure to food and water
      contaminated with ClO(4)(-) is common in the U.S. population, and the public
      health impact of such exposure is currently being debated. To date, it is still
      uncertain whether ClO(4)(-) is a NIS blocker or a transported substrate of NIS.
      Here we show in vitro and in vivo that NIS actively transports ClO(4)(-),
      including ClO(4)(-) translocation to the milk. A simple mathematical fluxes model
      accurately predicts the effect of ClO(4)(-) transport on the rate and extent of
      I(-) accumulation. Strikingly, the Na(+)/ ClO(4)(-) transport stoichiometry is
      electroneutral, uncovering that NIS translocates different substrates with
      different stoichiometries. That NIS actively concentrates ClO(4)(-) in maternal
      milk suggests that exposure of newborns to high levels of ClO(4)(-) may pose a
      greater health risk than previously acknowledged because ClO(4)(-) would thus
      directly inhibit the newborns' thyroidal I(-) uptake.

PMID- 18077371
TI  - The power of species sorting: local factors drive bacterial community composition
      over a wide range of spatial scales.
AB  - There is a vivid debate on the relative importance of local and regional factors
      in shaping microbial communities, and on whether microbial organisms show a
      biogeographic signature in their distribution. Taking a metacommunity approach,
      spatial factors can become important either through dispersal limitation (compare
      large spatial scales) or mass effects (in case of strongly connected systems). We
      here analyze two datasets on bacterial communities [characterized by community
      fingerprinting through denaturing gradient gel electrophoresis (DGGE)] in meso-
      to eutrophic shallow lakes to investigate the importance of spatial factors at
      three contrasting scales. Variation partitioning on datasets of both the
      bacterial communities of 11 shallow lakes that are part of a strongly
      interconnected and densely packed pond system <1 km apart, three groups of
      shallow lakes approximately 100 km apart, as well as these three groups of
      shallow lakes combined that span a large part of a North-South gradient in Europe
      (>2,500 km) shows a strong impact of local environmental factors on bacterial
      community composition, with a marginal impact of spatial distance. Our results
      indicate that dispersal is not strongly limiting even at large spatial scales,
      and that mass effects do not have a strong impact on bacterial communities even
      in physically connected systems. We suggest that the fast population growth rates
      of bacteria facilitate efficient species sorting along environmental gradients in
      bacterial communities over a very broad range of dispersal rates.

PMID- 18077372
TI  - A unified framework for linkage and association analysis of quantitative traits.
AB  - We give a unified treatment of the statistical foundations of population based
      association mapping and of family based linkage mapping of quantitative traits in
      humans. A central ingredient in the unification involves the efficient score
      statistic. The discussion focuses on generalized linear models with an additional
      illustration of the Cox (proportional hazards) model for age of onset data. We
      give analytic expressions for noncentrality parameters and show how they give
      qualitative insight into the loss of power that occurs if the scientist's assumed
      genetic model differs from nature's "true" genetic model. Issues to be studied in
      detail in the future development of this approach are discussed.

PMID- 18077373
TI  - Polymorphisms in human dopamine D2 receptor gene affect gene expression,
      splicing, and neuronal activity during working memory.
AB  - Subcortical dopamine D2 receptor (DRD2) signaling is implicated in cognitive
      processes and brain disorders, but the effect of DRD2 variants remains ambiguous.
      We measured allelic mRNA expression in postmortem human striatum and prefrontal
      cortex and then performed single nucleotide polymorphism (SNP) scans of the DRD2
      locus. A previously uncharacterized promoter SNP (rs12364283) located in a
      conserved suppressor region was associated with enhanced DRD2 expression, whereas
      previously studied DRD2 variants failed to affect expression. Moreover, two
      frequent intronic SNPs (rs2283265 and rs1076560) decreased expression of DRD2
      short splice variant (expressed mainly presynaptically) relative to DRD2 long
      (postsynaptic), a finding reproduced in vitro by using minigene constructs. Being
      in strong linkage disequilibrium with each other, both intronic SNPs (but not
      rs12364283) were also associated with greater activity of striatum and prefrontal
      cortex measured with fMRI during working memory and with reduced performance in
      working memory and attentional control tasks in healthy humans. Our results
      identify regulatory DRD2 polymorphisms that modify mRNA expression and splicing
      and working memory pathways.

PMID- 18077374
TI  - Dodecamer rotor ring defines H+/ATP ratio for ATP synthesis of prokaryotic V
      ATPase from Thermus thermophilus.
AB  - ATP synthesis by V-ATPase from the thermophilic bacterium Thermus thermophilus
      driven by the acid-base transition was investigated. The rate of ATP synthesis
      increased in parallel with the increase in proton motive force (PMF) >110 mV,
      which is composed of a difference in proton concentration (DeltapH) and the
      electrical potential differences (DeltaPsi) across membranes. The optimum rate of
      synthesis reached 85 s(-1), and the H(+)/ATP ratio of 4.0 +/- 0.1 was obtained.
      ATP was synthesized at a considerable rate solely by DeltapH, indicating DeltaPsi
      was not absolutely required for synthesis. Consistent with the H(+)/ATP ratio,
      cryoelectron micrograph images of 2D crystals of the membrane-bound rotor ring of
      the V-ATPase at 7.0-A resolution showed the presence of 12 V(o)-c subunits, each
      composed of two transmembrane helices. These results indicate that symmetry
      mismatch between the rotor and catalytic domains is not obligatory for rotary
      ATPases/synthases.

PMID- 18077375
TI  - MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting
      SuFu and Fus-1 expression.
AB  - MicroRNAs are single-stranded RNA of 18-24 nt expressed endogenously that play
      important roles in cancer development. Here, we show that expression of miR-378
      enhances cell survival, reduces caspase-3 activity, and promotes tumor growth and
      angiogenesis. Proteomic analysis indicates reduced expression of suppressor of
      fused (Sufu), a potential target of miR-378, which was confirmed in vitro and in
      vivo. Expression of a luciferase construct containing the target site in Sufu was
      repressed when cotransfected with miR-378. Transfection of a Sufu construct
      reversed the effect of miR-378, suggesting an important role for miR-378 in tumor
      cell survival. We also discovered that miR-378 targets Fus-1. Expression of
      luciferase constructs harboring the target sites in Fus-1 was repressed by miR
      378. Fus-1 constructs with or without its 3' UTR were also generated.
      Cotransfection experiments showed that the presence of miR-378 repressed Fus-1
      expression. Suppression of Fus-1 expression by siRNA against Fus-1 enhanced cell
      survival. Transfection of the Fus-1 construct reversed the function of miR-378 in
      cell survival. Our results suggest that miR-378 transfection enhanced cell
      survival, tumor growth, and angiogenesis through repression of the expression of
      two tumor suppressors, Sufu and Fus-1.

PMID- 18077376
TI  - Retrograde endocannabinoid signaling at striatal synapses requires a regulated
      postsynaptic release step.
AB  - Endocannabinoids (eCBs) mediate short- and long-term depression of synaptic
      strength by retrograde transsynaptic signaling. Previous studies have suggested
      that an eCB mobilization or release step in the postsynaptic neuron is involved
      in this retrograde signaling. However, it is not known whether this release
      process occurs automatically upon eCB synthesis or whether it is regulated by
      other synaptic factors. To address this issue, we loaded postsynaptic striatal
      medium spiny neurons (MSNs) with the eCBs anandamide (AEA) or 2
      arachidonoylglycerol and determined the conditions necessary for presynaptic
      inhibition. We found that presynaptic depression of glutamatergic excitatory
      postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents
      (IPSCs) induced by postsynaptic eCB loading required a certain level of afferent
      activation that varied between the different synaptic types. Synaptic depression
      at excitatory synapses was temperature-dependent and blocked by the eCB membrane
      transport blockers, VDM11 and UCM707, but did not require activation of
      metabotropic glutamate receptors, l-calcium channels, nitric oxide, voltage
      activated Na(+) channels, or intracellular calcium. Application of the CB(1)R
      antagonist, AM251, after depression was established, reversed the decrease in
      EPSC, but not in IPSC, amplitude. Direct activation of the CB(1) receptor by WIN
      55,212-2 initiated synaptic depression that was independent of afferent
      stimulation. These findings indicate that retrograde eCB signaling requires a
      postsynaptic release step involving a transporter or carrier that is activated by
      afferent stimulation/synaptic activation.

PMID- 18077377
TI  - Oncogenic H-Ras V12 promotes anchorage-independent cytokinesis in human
      fibroblasts.
AB  - Cell anchorage is required for cell proliferation of untransformed cells, whereas
      anchorage-independent growth can be induced by oncogenes and is a hallmark of
      transformation. Whereas anchorage-dependent control of the progression of the
      G(1) phase of the cell cycle has been extensively studied, it is less clear
      whether and how anchorage may control other cell cycle phases and whether
      oncogenes may affect such controls. Here, we found that lack of cell anchorage
      did not influence progression through the cell cycle S phase, G(2) phase, or most
      of mitosis of primary human fibroblasts. However, unanchored fibroblasts could
      not complete cytokinesis. The cleavage furrow and central spindle were still
      formed in the absence of anchorage, but cells were unable to complete ingression,
      causing binucleation. Importantly, V12 H-Ras-transformed fibroblasts and two
      cancer cell lines progressed through the entire cell cycle without anchorage,
      including through cytokinesis. This indicates that oncogenic signaling may
      contribute to anchorage-independent growth and tumorigenesis by promoting the
      final cleavage furrow ingression during cytokinesis.

PMID- 18077378
TI  - Estimation of multiple transmission rates for epidemics in heterogeneous
      populations.
AB  - One of the principal challenges in epidemiological modeling is to parameterize
      models with realistic estimates for transmission rates in order to analyze
      strategies for control and to predict disease outcomes. Using a combination of
      replicated experiments, Bayesian statistical inference, and stochastic modeling,
      we introduce and illustrate a strategy to estimate transmission parameters for
      the spread of infection through a two-phase mosaic, comprising favorable and
      unfavorable hosts. We focus on epidemics with local dispersal and formulate a
      spatially explicit, stochastic set of transition probabilities using a
      percolation paradigm for a susceptible-infected (S-I) epidemiological model. The
      S-I percolation model is further generalized to allow for multiple sources of
      infection including external inoculum and host-to-host infection. We fit the
      model using Bayesian inference and Markov chain Monte Carlo simulation to
      successive snapshots of damping-off disease spreading through replicated plant
      populations that differ in relative proportions of favorable and unfavorable
      hosts and with time-varying rates of transmission. Epidemiologically plausible
      parametric forms for these transmission rates are compared by using the deviance
      information criterion. Our results show that there are four transmission rates
      for a two-phase system, corresponding to each combination of infected donor and
      susceptible recipient. Knowing the number and magnitudes of the transmission
      rates allows the dominant pathways for transmission in a heterogeneous population
      to be identified. Finally, we show how failure to allow for multiple transmission
      rates can overestimate or underestimate the rate of spread of epidemics in
      heterogeneous environments, which could lead to marked failure or inefficiency of
      control strategies.

PMID- 18077379
TI  - Human neutrophils uniquely release TIMP-free MMP-9 to provide a potent catalytic
      stimulator of angiogenesis.
AB  - Several lines of evidence have implicated matrix metalloproteinase 9 (MMP-9) as a
      protease inducing an angiogenic switch critical for tumor progression. Among MMP
      9-expressing cell types, including cancer cells and tumor-associated leukocytes,
      inflammatory neutrophils appear to provide an important source of MMP-9 for tumor
      angiogenesis. However, delivery of MMP-9 by neutrophils has not been
      mechanistically linked to its catalytic activity at the angiogenic site. By using
      a modified angiogenic model, allowing for a direct analysis of exogenously added
      cells and their products in collagen onplants grafted on the chorioallantoic
      membrane of the chicken embryo, we demonstrate that intact human neutrophils and
      their granule contents are highly angiogenic. Furthermore, purified neutrophil
      MMP-9, isolated from the released granules as a zymogen (proMMP-9), constitutes a
      distinctly potent proangiogenic moiety inducing angiogenesis at subnanogram
      levels. The angiogenic response induced by neutrophil proMMP-9 required
      activation of the tissue inhibitor of metalloproteinases (TIMP)-free zymogen and
      the catalytic activity of the activated enzyme. That the high angiogenic potency
      of neutrophil proMMP-9 is associated with its unique TIMP-free status was
      confirmed when a generated and purified stoichiometric complex of neutrophil
      proMMP-9 with TIMP-1 failed to induce angiogenesis. Recombinant human proMMP-9,
      operationally free of TIMP-1, also induced angiogenesis at subnanomolar levels,
      but lost its proangiogenic potential when stoichiometrically complexed with TIMP
      1. Similar proMMP-9/TIMP-1 complexes, but naturally produced by human monocytic
      U937 cells and HT-1080 fibrosarcoma cells, did not stimulate angiogenesis. These
      findings provide biochemical evidence that infiltrating neutrophils, in contrast
      to other cell types, deliver a potent proangiogenic moiety, i.e., the
      unencumbered TIMP-free MMP-9.

PMID- 18077380
TI  - The genetic basis of a plant-insect coevolutionary key innovation.
AB  - Ehrlich and Raven formally introduced the concept of stepwise coevolution using
      butterfly and angiosperm interactions in an attempt to account for the impressive
      biological diversity of these groups. However, many biologists currently envision
      butterflies evolving 50 to 30 million years (Myr) after the major angiosperm
      radiation and thus reject coevolutionary origins of butterfly biodiversity. The
      unresolved central tenet of Ehrlich and Raven's theory is that evolution of plant
      chemical defenses is followed closely by biochemical adaptation in insect
      herbivores, and that newly evolved detoxification mechanisms result in adaptive
      radiation of herbivore lineages. Using one of their original butterfly-host plant
      systems, the Pieridae, we identify a pierid glucosinolate detoxification
      mechanism, nitrile-specifier protein (NSP), as a key innovation. Larval NSP
      activity matches the distribution of glucosinolate in their host plants.
      Moreover, by using five different temporal estimates, NSP seems to have evolved
      shortly after the evolution of the host plant group (Brassicales) ( approximately
      10 Myr). An adaptive radiation of these glucosinolate-feeding Pierinae followed,
      resulting in significantly elevated species numbers compared with related clades.
      Mechanistic understanding in its proper historical context documents more ancient
      and dynamic plant-insect interactions than previously envisioned. Moreover, these
      mechanistic insights provide the tools for detailed molecular studies of
      coevolution from both the plant and insect perspectives.

PMID- 18077381
TI  - Dynamic Stokes shift in green fluorescent protein variants.
AB  - Solvent reorganization around the excited state of a chromophore leads to an
      emission shift to longer wavelengths during the excited-state lifetime. This
      solvation response is absent in wild-type green fluorescent protein, and this has
      been attributed to rigidity in the chromophore's environment necessary to exclude
      nonradiative transitions to the ground state. The fluorescent protein mPlum was
      developed via directed evolution by selection for red emission, and we use time
      resolved fluorescence to study the dynamic Stokes shift through its evolutionary
      history. The far-red emission of mPlum is attributed to a picosecond solvation
      response that is observed at all temperatures above the glass transition. This
      time-dependent shift in emission is not observed in its evolutionary ancestors,
      suggesting that selective pressure has produced a chromophore environment that
      allows solvent reorganization. The evolutionary pathway and structures of related
      fluorescent proteins suggest the role of a single residue in close proximity to
      the chromophore as the primary cause of the solvation response.

PMID- 18077382
TI  - Life-history traits drive the evolutionary rates of mammalian coding and
      noncoding genomic elements.
AB  - A comprehensive phylogenetic framework is indispensable for investigating the
      evolution of genomic features in mammals as a whole, and particularly in humans.
      Using the ENCODE sequence data, we estimated mammalian neutral evolutionary rates
      and selective pressures acting on conserved coding and noncoding elements. We
      show that neutral evolutionary rates can be explained by the generation time (GT)
      hypothesis. Accordingly, primates (especially humans), having longer GTs than
      other mammals, display slower rates of neutral evolution. The evolution of
      constrained elements, particularly of nonsynonymous sites, is in agreement with
      the expectations of the nearly neutral theory of molecular evolution. We show
      that rates of nonsynonymous substitutions (dN) depend on the population size of a
      species. The results are robust to the exclusion of hypermutable CpG prone sites.
      The average rate of evolution in conserved noncoding sequences (CNCs) is 1.7
      times higher than in nonsynonymous sites. Despite this, CNCs evolve at similar or
      even lower rates than nonsynonymous sites in the majority of basal branches of
      the eutherian tree. This observation could be the result of an overall gradual
      or, alternatively, lineage-specific relaxation of CNCs. The latter hypothesis was
      supported by the finding that 3 of the 20 longest CNCs displayed significant
      relaxation of individual branches. This observation may explain why the evolution
      of CNCs fits the expectations of the nearly neutral theory less well than the
      evolution of nonsynonymous sites.

PMID- 18077383
TI  - Individual faces elicit distinct response patterns in human anterior temporal
      cortex.
AB  - Visual face identification requires distinguishing between thousands of faces we
      know. This computational feat involves a network of brain regions including the
      fusiform face area (FFA) and anterior inferotemporal cortex (aIT), whose roles in
      the process are not well understood. Here, we provide the first demonstration
      that it is possible to discriminate cortical response patterns elicited by
      individual face images with high-resolution functional magnetic resonance imaging
      (fMRI). Response patterns elicited by the face images were distinct in aIT but
      not in the FFA. Individual-level face information is likely to be present in both
      regions, but our data suggest that it is more pronounced in aIT. One
      interpretation is that the FFA detects faces and engages aIT for identification.

PMID- 18077384
TI  - Evasion of myofibroblasts from immune surveillance: a mechanism for tissue
      fibrosis.
AB  - Tissue fibrosis evolving from impaired tissue remodeling after injury is
      characterized by myofibroblast accumulation. We propose that during the
      development of fibrosis myofibroblasts acquire an immune-privileged cell
      phenotype, allowing their uninterrupted accumulation. Using the murine model of
      bleomycin-induced lung fibrosis in mice, we show that myofibroblasts that
      accumulate in lungs with fibrosis, but not in normal lungs, kill Fas(+)
      lymphocytes, resist Fas-induced apoptosis, and survive longer when grafted into
      allogeneic mice. In contrast, bleomycin-treated FasLigand (FasL)-deficient (gld)
      chimeric mice did not accumulate myofibroblasts or collagen in their lungs, and
      their FasL(-) myofibroblasts did not survive after alloengraftment. This finding
      indicates that myofibroblasts possess Fas/FasL-pathway-dependent characteristics
      that allow them to escape from immune surveillance and resulting organ fibrosis.

PMID- 18077385
TI  - Glass transition and rheological redundancy in F-actin solutions.
AB  - The unique mechanical performance of animal cells and tissues is attributed
      mostly to their internal biopolymer meshworks. Its perplexing universality and
      robustness against structural modifications by drugs and mutations is an enigma
      in cell biology and provides formidable challenges to materials science. Recent
      investigations could pinpoint highly universal patterns in the soft glassy
      rheology and nonlinear elasticity of cells and reconstituted networks. Here, we
      report observations of a glass transition in semidilute F-actin solutions, which
      could hold the key to a unified explanation of these phenomena. Combining
      suitable rheological protocols with high-precision dynamic light scattering, we
      can establish a remarkable rheological redundancy and trace it back to a highly
      universal exponential stretching of the single-polymer relaxation spectrum of a
      "glassy wormlike chain." By exploiting the ensuing generalized time-temperature
      superposition principle, the time domain accessible to microrheometry can be
      extended by several orders of magnitude, thus opening promising new metrological
      opportunities.

PMID- 18077386
TI  - Gap junction remodeling and cardiac arrhythmogenesis in a murine model of
      oculodentodigital dysplasia.
AB  - Gap junction channels are required for normal cardiac impulse propagation, and
      gap junction remodeling is associated with enhanced arrhythmic risk.
      Oculodentodigital dysplasia (ODDD) is a multisystem syndrome due to mutations in
      the connexin43 (Cx43) gap junction channel gene. To determine the effects of a
      human connexin channelopathy on cardiac electrophysiology and arrhythmogenesis,
      we generated a murine model of ODDD by introducing the disease-causing I130T
      mutant allele into the mouse genome. Cx43 abundance was markedly reduced in
      mutant hearts with preferential loss of phosphorylated forms that interfered with
      trafficking and assembly of gap junctions in the junctional membrane. Dual whole
      cell patch-clamp studies showed significantly lower junctional conductance
      between neonatal cell pairs from mutant hearts, and optical mapping of isolated
      perfused hearts with voltage-sensitive dyes demonstrated significant slowing of
      conduction velocity. Programmed electrical stimulation revealed a markedly
      increased susceptibility to spontaneous and inducible ventricular
      tachyarrhythmias. In summary, our data demonstrate that the I130T mutation
      interferes with Cx43 posttranslational processing, resulting in diminished cell
      cell coupling, slowing of impulse propagation, and a proarrhythmic substrate.

PMID- 18077387
TI  - Soj (ParA) DNA binding is mediated by conserved arginines and is essential for
      plasmid segregation.
AB  - Soj is a member of the ParA family of ATPases involved in plasmid and chromosomal
      segregation. It binds nonspecifically and cooperatively to DNA although the
      function of this binding is unknown. Here, we show that mutation of conserved
      arginine residues that map to the surface of Bacillus subtilis Soj caused only
      minimal effects on nucleotide-dependent dimerization but had dramatic effects on
      DNA binding. Using a model plasmid partitioning system in Escherichia coli, we
      find that Soj DNA-binding mutants are deficient in plasmid segregation. The
      location of the arginines on the Soj structure explains why DNA binding depends
      on dimerization and was used to orient the Soj dimer on the DNA, revealing the
      axis of Soj polymerization. The arginine residues are conserved among other
      chromosomal homologues, including the ParAs from Caulobacter crescentus,
      Pseudomonas aeruginosa, Pseudomonas putida, Streptomyces coelicolor, and
      chromosome I of Vibrio cholerae indicating that DNA binding is a common feature
      of members of this family.

PMID- 18077388
TI  - Activation mechanism of a noncanonical RNA-dependent RNA polymerase.
AB  - Two lineages of viral RNA-dependent RNA polymerases (RDRPs) differing in the
      organization (canonical vs. noncanonical) of the palm subdomain have been
      identified. Phylogenetic analyses indicate that both lineages diverged at a very
      early stage of the evolution of the enzyme [Gorbalenya AE, Pringle FM, Zeddam JL,
      Luke BT, Cameron CE, Kalmakoff J, Hanzlik TN, Gordon KH, Ward VK (2002) J Mol
      Biol 324:47-62]. Here, we report the x-ray structure of a noncanonical birnaviral
      RDRP, named VP1, in its free form, bound to Mg(2+) ions, and bound to a peptide
      representing the polymerase-binding motif of the regulatory viral protein VP3.
      The structure of VP1 reveals that the noncanonical connectivity of the palm
      subdomain maintains the geometry of the catalytic residues found in canonical
      polymerases but results in a partial blocking of the active site cavity. The VP1
      VP3 peptide complex shows a mode of polymerase activation in which VP3 binding
      promotes a conformational change that removes the steric blockade of the VP1
      active site, facilitating the accommodation of the template and incoming
      nucleotides for catalysis. The striking structural similarities between
      birnavirus (dsRNA) and the positive-stranded RNA picornavirus and calicivirus
      RDRPs provide evidence supporting the existence of functional and evolutionary
      relationships between these two virus groups.

PMID- 18077389
TI  - Replacement of Igamma3 germ-line promoter by Igamma1 inhibits class-switch
      recombination to IgG3.
AB  - Class-switch recombination (CSR) enables IgM-producing B cells to switch to the
      production of IgG, IgE, and IgA. The process requires germ-line (GL)
      transcription that initiates from promoters upstream of switch (S) sequences and
      is regulated by the 3' regulatory region (3'RR) located downstream of the Ig
      heavy chain (IgH) locus. How the 3'RR effect its long-range activation is
      presently unclear. We generated a mouse line in which Igamma3 GL promoter was
      replaced by Igamma1. We found that GL transcription could initiate from the
      inserted Igamma1 promoter and was induced by increased concentrations of IL-4 and
      that the transcripts were normally spliced. However, when compared with GL
      transcripts derived from the endogenous Igamma1 promoter in the same stimulation
      conditions, those from the inserted Igamma1 promoter were less abundant. CSR to
      Cgamma3 was abrogated both in vivo and in vitro. The results strongly suggest
      that the endogenous Igamma1 promoter insulates the inserted Igamma1 from the long
      range activating effect of the 3'RR. The implications of our findings are
      discussed in light of the prominent models of long-distance activation in complex
      loci.

PMID- 18077390
TI  - Genomic drift and copy number variation of sensory receptor genes in humans.
AB  - The number of sensory receptor genes varies extensively among different mammalian
      species. This variation is believed to be caused partly by physiological
      requirements of animals and partly by genomic drift due to random duplication and
      deletion of genes. If the contribution of genomic drift is substantial, each
      species should contain a significant amount of copy number variation (CNV). We
      therefore investigated CNVs in sensory receptor genes among 270 healthy humans by
      using published CNV data. The results indicated that olfactory receptor (OR),
      taste receptor type 2, and vomeronasal receptor type 1 genes show a high level of
      intraspecific CNVs. In particular, >30% of the approximately 800 OR gene loci in
      humans were polymorphic with respect to copy number, and two randomly chosen
      individuals showed a copy number difference of approximately 11 in functional OR
      genes on average. There was no significant difference in the amount of CNVs
      between functional and nonfunctional OR genes. Because pseudogenes are expected
      to evolve in a neutral fashion, this observation suggests that functional OR
      genes also have evolved in a similar manner with respect to copy number change.
      In addition, we found that the evolutionary change of copy number of OR genes
      approximately follows the Gaussian process in probability theory, and the copy
      number divergence between populations has increased with evolutionary time. We
      therefore conclude that genomic drift plays an important role for generating
      intra- and interspecific CNVs of sensory receptor genes. Similar results were
      obtained when all annotated genes were analyzed.

PMID- 18077391
TI  - Hematopoietic prostaglandin D2 synthase controls the onset and resolution of
      acute inflammation through PGD2 and 15-deoxyDelta12 14 PGJ2.
AB  - Hematopoietic prostaglandin D(2) synthase (hPGD(2)S) metabolizes cyclooxygenase
      (COX)-derived PGH(2) to PGD(2) and 15-deoxyDelta(12-14) PGJ(2) (15d-PGJ(2)).
      Unlike COX, the role of hPGD(2)S in host defense is ambiguous. PGD(2) can be
      either pro- or antiinflammatory depending on disease etiology, whereas the
      existence of 15d-PGJ(2) and its relevance to pathophysiology remain
      controversial. Herein, studies on hPGD(2)S KO mice reveal that 15d-PGJ(2) is
      synthesized in a self-resolving peritonitis, detected by using liquid
      chromatography-tandem MS. Together with PGD(2) working on its DP1 receptor, 15d
      PGJ(2) controls the balance of pro- vs. antiinflammatory cytokines that regulate
      leukocyte influx and monocyte-derived macrophage efflux from the inflamed
      peritoneal cavity to draining lymph nodes leading to resolution. Specifically,
      inflammation in hPGD(2)S KOs is more severe during the onset phase arising from a
      substantial cytokine imbalance resulting in enhanced polymorphonuclear leukocyte
      and monocyte trafficking. Moreover, resolution is impaired, characterized by
      macrophage and surprisingly lymphocyte accumulation. Data from this work place
      hPGD(2)S at the center of controlling the onset and the resolution of acute
      inflammation where it acts as a crucial checkpoint controller of
      cytokine/chemokine synthesis as well as leukocyte influx and efflux. Here, we
      provide definitive proof that 15d-PGJ(2) is synthesized during mammalian
      inflammatory responses, and we highlight DP1 receptor activation as a potential
      antiinflammatory strategy.

PMID- 18077392
TI  - Environmental impacts of divorce.
AB  - Divorce is increasingly common around the world. Its causes, dynamics, and
      socioeconomic impacts have been widely studied, but little research has addressed
      its environmental impacts. We found that average household size (number of people
      in a household) in divorced households (households with divorced heads) was 27
      41% smaller than married households (households with married heads) in 12
      countries across the world around the year 2000 (between 1998 and 2002). If
      divorced households had combined to have the same average household size as
      married households, there could have been 7.4 million fewer households in these
      countries. Meanwhile, the number of rooms per person in divorced households was
      33-95% greater than in married households. In the United States (U.S.) in 2005,
      divorced households spent 46% and 56% more on electricity and water per person
      than married households. Divorced households in the U.S. could have saved more
      than 38 million rooms, 73 billion kilowatt-hours of electricity, and 627 billion
      gallons of water in 2005 alone if their resource-use efficiency had been
      comparable to married households. Furthermore, U.S. households that experienced
      divorce used 42-61% more resources per person than before their dissolution.
      Remarriage of divorced household heads increased household size and reduced
      resource use to levels similar to those of married households. The results
      suggest that mitigating the impacts of resource-inefficient lifestyles such as
      divorce helps to achieve global environmental sustainability and saves money for
      households.

PMID- 18077393
TI  - Reciprocity between phase shifts and amplitude changes in the mammalian circadian
      clock.
AB  - Circadian rhythms help organisms adapt to predictable daily changes in their
      environment. Light resets the phase of the underlying oscillator to maintain the
      organism in sync with its surroundings. Light also affects the amplitude of overt
      rhythms. At a critical phase during the night, when phase shifts are maximal,
      light can reduce rhythm amplitude to nearly zero, whereas in the subjective day,
      when phase shifts are minimal, it can boost amplitude substantially. To explore
      the cellular basis for this reciprocal relationship between phase shift and
      amplitude change, we generated a photoentrainable, cell-based system in mammalian
      fibroblasts that shares several key features of suprachiasmatic nucleus light
      entrainment. Upon light stimulation, these cells exhibit calcium/cyclic AMP
      responsive element-binding (CREB) protein phosphorylation, leading to temporally
      gated acute induction of the Per2 gene, followed by phase-dependent changes in
      phase and/or amplitude of the PER2 circadian rhythm. At phases near the PER2
      peak, photic stimulation causes little phase shift but enhanced rhythm amplitude.
      At phases near the PER2 nadir, on the other hand, the same stimuli cause large
      phase shifts but dampen rhythm amplitude. Real-time monitoring of PER2
      oscillations in single cells reveals that changes in both synchrony and amplitude
      of individual oscillators underlie these phenomena.

PMID- 18077394
TI  - Biogenic formation of photoactive arsenic-sulfide nanotubes by Shewanella sp.
      strain HN-41.
AB  - Microorganisms facilitate the formation of a wide range of minerals that have
      unique physical and chemical properties as well as morphologies that are not
      produced by abiotic processes. Here, we report the production of an extensive
      extracellular network of filamentous, arsenic-sulfide (As-S) nanotubes (20-100 nm
      in diameter by approximately 30 mum in length) by the dissimilatory metal
      reducing bacterium Shewanella sp. HN-41. The As-S nanotubes, formed via the
      reduction of As(V) and S(2)O(3)(2-), were initially amorphous As(2)S(3) but
      evolved with increasing incubation time toward polycrystalline phases of the
      chalcogenide minerals realgar (AsS) and duranusite (As(4)S). Upon maturation, the
      As-S nanotubes behaved as metals and semiconductors in terms of their electrical
      and photoconductive properties, respectively. The As-S nanotubes produced by
      Shewanella may provide useful materials for novel nano- and opto-electronic
      devices.

PMID- 18077395
TI  - Ubc13/Rnf8 ubiquitin ligases control foci formation of the
      Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage.
AB  - The Brca1 A complex contains Brca1/Bard1, Abraxas, Rap80, and Brcc36; however,
      with the exception of the Brca1-Abraxas interaction, how the A complex is
      assembled is not known. The A complex is localized to sites of DNA damage through
      the UIM domains of RAP80, which bind K63-linked polyubiquitin chains. In this
      study, we identified an FHA domain RING finger E3 ubiquitin ligase, RNF8, and an
      E2-conjugating enzyme known to form K63-polyubiquitin chains, Ubc13, each of
      which is required to recruit the Brca1 A complex to sites of DNA damage. Rnf8
      localizes to sites of DNA damage through an FHA-domain-containing region. We
      found that Rap80 contains an Abraxas interaction domain [AIR (Abraxas-interacting
      region)], required for association of Rap80 with Abraxas, Brca1, and Brcc36.
      Abraxas and Brcc36 associate through coiled-coil domains on each protein. These
      data suggest a model through which Ubc13 and Rnf8 are recruited to sites of DNA
      damage through DNA-damage-induced phosphorylation of a chromatin-associated
      protein and generate polyubiquitin chains that then recruit Rap80 and the entire
      Brca1 A complex to DNA-damage foci. This sequential E3 ubiquitin ligase
      recruitment constitutes a ubiquitin ligase cascade required for DNA repair and
      checkpoint signaling.

PMID- 18077396
TI  - New apes fill the gap.

PMID- 18077397
TI  - Neuro-anatomic evidence for the maturational delay hypothesis of ADHD.

PMID- 18077398
TI  - Profile of Steven Henikoff.

PMID- 18077399
TI  - Climate change and the adequacy of food and timber in the 21st century.

PMID- 18077400
TI  - The impact of climate change on smallholder and subsistence agriculture.
AB  - Some of the most important impacts of global climate change will be felt among
      the populations, predominantly in developing countries, referred to as
      "subsistence" or "smallholder" farmers. Their vulnerability to climate change
      comes both from being predominantly located in the tropics, and from various
      socioeconomic, demographic, and policy trends limiting their capacity to adapt to
      change. However, these impacts will be difficult to model or predict because of
      (i) the lack of standardised definitions of these sorts of farming system, and
      therefore of standard data above the national level, (ii) intrinsic
      characteristics of these systems, particularly their complexity, their location
      specificity, and their integration of agricultural and nonagricultural livelihood
      strategies, and (iii) their vulnerability to a range of climate-related and other
      stressors. Some recent work relevant to these farming systems is reviewed, a
      conceptual framework for understanding the diverse forms of impacts in an
      integrated manner is proposed, and future research needs are identified.

PMID- 18077401
TI  - Crop and pasture response to climate change.
AB  - We review recent research of importance to understanding crop and pasture plant
      species response to climate change. Topics include plant response to elevated
      CO(2) concentration, interactions with climate change variables and air
      pollutants, impacts of increased climate variability and frequency of extreme
      events, the role of weeds and pests, disease and animal health, issues in
      biodiversity, and vulnerability of soil carbon pools. We critically analyze the
      links between fundamental knowledge at the plant and plot level and the
      additional socio-economic variables that determine actual production and trade of
      food at regional to global scales. We conclude by making recommendations for
      current and future research needs, with a focus on continued and improved
      integration of experimental and modeling efforts.

PMID- 18077402
TI  - Adapting agriculture to climate change.
AB  - The strong trends in climate change already evident, the likelihood of further
      changes occurring, and the increasing scale of potential climate impacts give
      urgency to addressing agricultural adaptation more coherently. There are many
      potential adaptation options available for marginal change of existing
      agricultural systems, often variations of existing climate risk management. We
      show that implementation of these options is likely to have substantial benefits
      under moderate climate change for some cropping systems. However, there are
      limits to their effectiveness under more severe climate changes. Hence, more
      systemic changes in resource allocation need to be considered, such as targeted
      diversification of production systems and livelihoods. We argue that achieving
      increased adaptation action will necessitate integration of climate change
      related issues with other risk factors, such as climate variability and market
      risk, and with other policy domains, such as sustainable development. Dealing
      with the many barriers to effective adaptation will require a comprehensive and
      dynamic policy approach covering a range of scales and issues, for example, from
      the understanding by farmers of change in risk profiles to the establishment of
      efficient markets that facilitate response strategies. Science, too, has to
      adapt. Multidisciplinary problems require multidisciplinary solutions, i.e., a
      focus on integrated rather than disciplinary science and a strengthening of the
      interface with decision makers. A crucial component of this approach is the
      implementation of adaptation assessment frameworks that are relevant, robust, and
      easily operated by all stakeholders, practitioners, policymakers, and scientists.

PMID- 18077403
TI  - Climate change impacts on forestry.
AB  - Changing temperature and precipitation pattern and increasing concentrations of
      atmospheric CO(2) are likely to drive significant modifications in natural and
      modified forests. Our review is focused on recent publications that discuss the
      changes in commercial forestry, excluding the ecosystem functions of forests and
      nontimber forest products. We concentrate on potential direct and indirect
      impacts of climate change on forest industry, the projections of future trends in
      commercial forestry, the possible role of biofuels, and changes in supply and
      demand.

PMID- 18077404
TI  - Global food security under climate change.
AB  - This article reviews the potential impacts of climate change on food security. It
      is found that of the four main elements of food security, i.e., availability,
      stability, utilization, and access, only the first is routinely addressed in
      simulation studies. To this end, published results indicate that the impacts of
      climate change are significant, however, with a wide projected range (between 5
      million and 170 million additional people at risk of hunger by 2080) strongly
      depending on assumed socio-economic development. The likely impacts of climate
      change on the other important dimensions of food security are discussed
      qualitatively, indicating the potential for further negative impacts beyond those
      currently assessed with models. Finally, strengths and weaknesses of current
      assessment studies are discussed, suggesting improvements and proposing avenues
      for new analyses.

PMID- 18077405
TI  - Global fish production and climate change.
AB  - Current global fisheries production of approximately 160 million tons is rising
      as a result of increases in aquaculture production. A number of climate-related
      threats to both capture fisheries and aquaculture are identified, but we have low
      confidence in predictions of future fisheries production because of uncertainty
      over future global aquatic net primary production and the transfer of this
      production through the food chain to human consumption. Recent changes in the
      distribution and productivity of a number of fish species can be ascribed with
      high confidence to regional climate variability, such as the El Nino-Southern
      Oscillation. Future production may increase in some high-latitude regions because
      of warming and decreased ice cover, but the dynamics in low-latitude regions are
      governed by different processes, and production may decline as a result of
      reduced vertical mixing of the water column and, hence, reduced recycling of
      nutrients. There are strong interactions between the effects of fishing and the
      effects of climate because fishing reduces the age, size, and geographic
      diversity of populations and the biodiversity of marine ecosystems, making both
      more sensitive to additional stresses such as climate change. Inland fisheries
      are additionally threatened by changes in precipitation and water management. The
      frequency and intensity of extreme climate events is likely to have a major
      impact on future fisheries production in both inland and marine systems. Reducing
      fishing mortality in the majority of fisheries, which are currently fully
      exploited or overexploited, is the principal feasible means of reducing the
      impacts of climate change.

PMID- 18077409
TI  - Other-regarding preferences in a non-human primate: common marmosets provision
      food altruistically.
AB  - Human cooperation is unparalleled in the animal world and rests on an altruistic
      concern for the welfare of genetically unrelated strangers. The evolutionary
      roots of human altruism, however, remain poorly understood. Recent evidence
      suggests a discontinuity between humans and other primates because individual
      chimpanzees do not spontaneously provide food to other group members, indicating
      a lack of concern for their welfare. Here, we demonstrate that common marmoset
      monkeys (Callithrix jacchus) do spontaneously provide food to nonreciprocating
      and genetically unrelated individuals, indicating that other-regarding
      preferences are not unique to humans and that their evolution did not require
      advanced cognitive abilities such as theory of mind. Because humans and marmosets
      are cooperative breeders and the only two primate taxa in which such unsolicited
      prosociality has been found, we conclude that these prosocial predispositions may
      emanate from cooperative breeding.

PMID- 18077410
TI  - Structural insight into distinct mechanisms of protease inhibition by antibodies.
AB  - To better understand how the relatively flat antigen-combining sites of
      antibodies interact with the concave shaped substrate-binding clefts of
      proteases, we determined the structures of two antibodies in complex with the
      trypsin-like hepatocyte growth-factor activator (HGFA). The two inhibitory
      antibodies, Ab58 and Ab75, were generated from a human Fab phage display library
      with synthetic diversity in the three complementarity determining regions (H1,
      H2, and H3) of the heavy chain, mimicking the natural diversity of the human Ig
      repertoire. Biochemical studies and the structures of the Fab58:HGFA (3.5-A
      resolution) and the Fab75:HGFA (2.2-A resolution) complexes revealed that Ab58
      obstructed substrate access to the active site, whereas Ab75 allosterically
      inhibited substrate hydrolysis. In both cases, the antibodies interacted with the
      same protruding element (99-loop), which forms part of the substrate-binding
      cleft. Ab58 inserted its H1 and H2 loops in the cleft to occupy important
      substrate interaction sites (S3 and S2). In contrast, Ab75 bound at the backside
      of the cleft to a region corresponding to thrombin exosite II, which is known to
      interact with allosteric effector molecules. In agreement with the structural
      analysis, binding assays with active site inhibitors and enzymatic assays showed
      that Ab58 is a competitive inhibitor, and Ab75 is a partial competitive
      inhibitor. These results provide structural insight into antibody-mediated
      protease inhibition. They suggest that unlike canonical inhibitors, antibodies
      may preferentially target protruding loops at the rim of the substrate-binding
      cleft to interfere with the catalytic machinery of proteases without requiring
      long insertion loops.

PMID- 18077411
TI  - Real-time observation of bacteriophage T4 gp41 helicase reveals an unwinding
      mechanism.
AB  - Helicases are enzymes that couple ATP hydrolysis to the unwinding of double
      stranded (ds) nucleic acids. The bacteriophage T4 helicase (gp41) is a hexameric
      helicase that promotes DNA replication within a highly coordinated protein
      complex termed the replisome. Despite recent progress, the gp41 unwinding
      mechanism and regulatory interactions within the replisome remain unclear. Here
      we use a single tethered DNA hairpin as a real-time reporter of gp41-mediated
      dsDNA unwinding and single-stranded (ss) DNA translocation with 3-base pair (bp)
      resolution. Although gp41 translocates on ssDNA as fast as the in vivo
      replication fork ( approximately 400 bp/s), its unwinding rate extrapolated to
      zero force is much slower ( approximately 30 bp/s). Together, our results have
      two implications: first, gp41 unwinds DNA through a passive mechanism; second,
      this weak helicase cannot efficiently unwind the T4 genome alone. Our results
      suggest that important regulations occur within the replisome to achieve rapid
      and processive replication.

PMID- 18077412
TI  - Metabotyping of Caenorhabditis elegans reveals latent phenotypes.
AB  - Assigning functions to every gene in a living organism is the next challenge for
      functional genomics. In fact, 85-90% of the 19,000 genes of the nematode
      Caenorhabditis elegans genome do not produce any visible phenotype when
      inactivated, which hampers determining their function, especially when they do
      not belong to previously characterized gene families. We used (1)H high
      resolution magic angle spinning NMR spectroscopy ((1)H HRMAS-NMR) to reveal the
      latent phenotype associated to superoxide dismutase (sod-1) and catalase (ctl-1)
      C. elegans mutations, both involved in the elimination of radical oxidative
      species. These two silent mutations are significantly discriminated from the wild
      type strain and from each other. We identify a metabotype significantly
      associated with these mutations involving a general reduction of fatty acyl
      resonances from triglycerides, unsaturated lipids being known targets of free
      radicals. This work opens up perspectives for the use of (1)H HRMAS-NMR as a
      molecular phenotyping device for model organisms. Because it is amenable to high
      throughput and is shown to be highly informative, this approach may rapidly lead
      to a functional and integrated metabonomic mapping of the C. elegans genome at
      the systems biology level.

PMID- 18077413
TI  - Principles underlying energetic coupling along an allosteric communication
      trajectory of a voltage-activated K+ channel.
AB  - The information flow between distal elements of a protein may rely on allosteric
      communication trajectories lying along the protein's tertiary or quaternary
      structure. To unravel the underlying features of energy parsing along allosteric
      pathways in voltage-gated K(+) channels, high-order thermodynamic coupling
      analysis was performed. We report that such allosteric trajectories are
      functionally conserved and delineated by well defined boundaries. Moreover,
      allosteric trajectories assume a hierarchical organization whereby increasingly
      stronger layers of cooperative residue interactions act to ensure efficient and
      cooperative long-range coupling between distal channel regions. Such long-range
      communication is brought about by a coupling of local and global conformational
      changes, suggesting that the allosteric trajectory also corresponds to a pathway
      of physical deformation. Supported by theoretical analyses and analogy to studies
      analyzing the contribution of long-range residue coupling to protein stability,
      we propose that such experimentally derived trajectory features are a general
      property of allosterically regulated proteins.

PMID- 18077414
TI  - Localizing frustration in native proteins and protein assemblies.
AB  - We propose a method of quantifying the degree of frustration manifested by
      spatially local interactions in protein biomolecules. This method of localization
      smoothly generalizes the global criterion for an energy landscape to be funneled
      to the native state, which is in keeping with the principle of minimal
      frustration. A survey of the structural database shows that natural proteins are
      multiply connected by a web of local interactions that are individually minimally
      frustrated. In contrast, highly frustrated interactions are found clustered on
      the surface, often near binding sites. These binding sites become less frustrated
      upon complex formation.

PMID- 18077415
TI  - Consequences of localized frustration for the folding mechanism of the IM7
      protein.
AB  - In the laboratory, IM7 has been found to have an unusual folding mechanism in
      which an "on-pathway" intermediate with nonnative interactions is formed. We show
      that this intermediate is a consequence of an unusual cluster of highly
      frustrated interactions in the native structure. This cluster is involved in the
      binding of IM7 to its target, Colicin E7. Redesign of residues in this cluster to
      eliminate frustration is predicted by simulations to lead to faster folding
      without the population of an intermediate ensemble.

PMID- 18077416
TI  - How processing of aspartylphosphate is coupled to lumenal gating of the ion
      pathway in the calcium pump.
AB  - Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum is the best-studied
      member of the P-type or E1/E2 type ion transporting ATPases. It has been
      crystallized in seven different states that cover nearly the entire reaction
      cycle. Here we describe the structure of this ATPase complexed with phosphate
      analogs BeF(3)(-) and AlF(4)(-) in the absence of Ca(2+), which correspond to the
      E2P ground state and E2 approximately P transition state, respectively. The
      luminal gate is open with BeF(3)(-) and closed with AlF(4)(-). These and the E1
      approximately P.ADP analog crystal structures show that a two-step rotation of
      the cytoplasmic A-domain opens and closes the luminal gate through the movements
      of the M1-M4 transmembrane helices. There are several conformational switches
      coupled to the rotation, and the one in the cytoplasmic part of M2 has critical
      importance. In the second step of rotation, positioning of one water molecule
      couples the hydrolysis of aspartylphosphate to closing of the gate.

PMID- 18077417
TI  - ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15.
AB  - The ERK pathway responds to extracellular stimuli and oncogenes by modulating
      cellular processes, including transcription, adhesion, survival, and
      proliferation. ERK has diverse substrates that carry out these functions. The
      processes that are modulated are determined in part by the substrates that ERK
      phosphorylates. We demonstrate that PEA-15 (phosphoprotein enriched in
      astrocytes, 15 kDa) targets ERK to RSK2 and thereby enhances RSK2 activation. PEA
      15 independently bound ERK and RSK2 and increased ERK association with RSK2 in a
      concentration-dependent manner. PEA-15 increased RSK2 activity and CREB-mediated
      transcription, and this process was regulated by phosphorylation of PEA-15.
      Finally, phorbol ester stimulation of PEA-15-null lymphocytes resulted in
      impaired RSK2 activation that was rescued by exogenous PEA-15 expression.
      Therefore, PEA-15 functions as a scaffold to enhance ERK activation of RSK2, and
      this activity is regulated by phosphorylation. Thus, PEA-15 can integrate signal
      transduction to provide a specific physiological outcome from activation of the
      multipotent ERK MAP kinase pathway.

PMID- 18077418
TI  - Profiling of UV-induced ATM/ATR signaling pathways.
AB  - To ensure survival in the face of genomic insult, cells have evolved complex
      mechanisms to respond to DNA damage, termed the DNA damage checkpoint. The
      serine/threonine kinases ataxia telangiectasia-mutated (ATM) and ATM and Rad3
      related (ATR) activate checkpoint signaling by phosphorylating substrate proteins
      at SQ/TQ motifs. Although some ATM/ATR substrates (Chk1, p53) have been
      identified, the lack of a more complete list of substrates limits current
      understanding of checkpoint pathways. Here, we use immunoaffinity phosphopeptide
      isolation coupled with mass spectrometry to identify 570 sites phosphorylated in
      UV-damaged cells, 498 of which are previously undescribed. Semiquantitative
      analysis yielded 24 known and 192 previously uncharacterized sites differentially
      phosphorylated upon UV damage, some of which were confirmed by SILAC, Western
      blotting, and immunoprecipitation/Western blotting. ATR-specific phosphorylation
      was investigated by using a Seckel syndrome (ATR mutant) cell line. Together,
      these results provide a rich resource for further deciphering ATM/ATR signaling
      and the pathways mediating the DNA damage response.

PMID- 18077419
TI  - Runx2 deficiency and defective subnuclear targeting bypass senescence to promote
      immortalization and tumorigenic potential.
AB  - The osteogenic Runt-related (Runx2) transcription factor negatively regulates
      proliferation and ribosomal gene expression in normal diploid osteoblasts, but is
      up-regulated in metastatic breast and prostate cancer cells. Thus, Runx2 may
      function as a tumor suppressor or an oncogene depending on the cellular context.
      Here we show that Runx2-deficient primary osteoblasts fail to undergo senescence
      as indicated by the absence of beta-gal activity and p16(INK4a) tumor suppressor
      expression. Primary Runx2-null osteoblasts have a growth advantage and exhibit
      loss of p21(WAF1/CIP1) and p19(ARF) expression. Reintroduction of WT Runx2, but
      not a subnuclear targeting-defective mutant, induces both p21(WAF/CIP1) and
      p19(ARF) mRNA and protein resulting in cell-cycle inhibition. Accumulation of
      spontaneous phospho-H2A.X foci, loss of telomere integrity and the
      Mre11/Rad50/Nbs1 DNA repair complex, and a delayed DNA repair response all
      indicate that Runx2 deficiency leads to genomic instability. We propose that
      Runx2 functions as a tumor suppressor in primary diploid osteoblasts and that
      subnuclear targeting contributes to Runx2-mediated tumor suppression.

PMID- 18077420
TI  - Sonic Hedgehog promotes the development of multipotent neural crest progenitors
      endowed with both mesenchymal and neural potentials.
AB  - In the vertebrate embryo, the cephalic neural crest cells (CNCCs) produce cells
      belonging to two main lineages: the neural [including neurons, glial cells of the
      peripheral nervous system (PNS), and melanocytes] and the mesenchymal
      (chondrocytes, osteoblasts, smooth muscle cells, and connective tissue cells),
      whereas the trunk NCCs (TNCCs) in amniotes yield only neural derivatives.
      Although multipotent cells have previously been evidenced by in vitro clonal
      analysis, the issue as to whether all of the mesenchymal and neural phenotypes
      can be derived from a unique NC stem cell has remained elusive. In the present
      work, we devised culture conditions that led us to identify a highly multipotent
      NCC endowed with both neural and mesenchymal potentials, which lies upstream of
      all the other NC progenitors known so far. We found that addition of recombinant
      Sonic Hedgehog (Shh) increased the number of CNCC progenitors yielding both
      mesenchymal and neural lineages and promoted the development of such precursors
      from the TNCC. Shh decreased the neural-restricted precursors without affecting
      the overall CNCC survival and proliferation. By showing a differential positive
      effect of Shh on the expression of mesenchymal phenotypes (i.e., chondrocytes and
      smooth muscle cells) by multipotent CNCCs, these results shed insights on the in
      vivo requirement of Shh for craniofacial morphogenesis. Together with
      evolutionary considerations, these data also suggest that the mesenchymal-neural
      precursor represents the ancestral form of the NC stem cell, which in extinct
      forms of vertebrates (the ostracoderms) was able to yield both the PNS and
      superficial skeleton.

PMID- 18077421
TI  - Exceptionally well preserved late Quaternary plant and vertebrate fossils from a
      blue hole on Abaco, The Bahamas.
AB  - We report Quaternary vertebrate and plant fossils from Sawmill Sink, a "blue
      hole" (a water-filled sinkhole) on Great Abaco Island, The Bahamas. The fossils
      are well preserved because of deposition in anoxic salt water. Vertebrate fossils
      from peat on the talus cone are radiocarbon-dated from approximately 4,200 to
      1,000 cal BP (Late Holocene). The peat produced skeletons of two extinct species
      (tortoise Chelonoidis undescribed sp. and Caracara Caracara creightoni) and two
      extant species no longer in The Bahamas (Cuban crocodile, Crocodylus rhombifer;
      and Cooper's or Gundlach's Hawk, Accipiter cooperii or Accipiter gundlachii). A
      different, inorganic bone deposit on a limestone ledge in Sawmill Sink is a Late
      Pleistocene owl roost that features lizards (one species), snakes (three
      species), birds (25 species), and bats (four species). The owl roost fauna
      includes Rallus undescribed sp. (extinct; the first Bahamian flightless rail) and
      four other locally extinct species of birds (Cooper's/Gundlach's Hawk, A.
      cooperii/gundlachii; flicker Colaptes sp.; Cave Swallow, Petrochelidon fulva; and
      Eastern Meadowlark, Sturnella magna) and mammals (Bahamian hutia, Geocapromys
      ingrahami; and a bat, Myotis sp.). The exquisitely preserved fossils from Sawmill
      Sink suggest a grassy pineland as the dominant plant community on Abaco in the
      Late Pleistocene, with a heavier component of coppice (tropical dry evergreen
      forest) in the Late Holocene. Important in its own right, this information also
      will help biologists and government planners to develop conservation programs in
      The Bahamas that consider long-term ecological and cultural processes.

PMID- 18077422
TI  - Rapid diversification and dispersal during periods of global warming by
      plethodontid salamanders.
AB  - A phylogeny and timescale derived from analyses of multilocus nuclear DNA
      sequences for Holarctic genera of plethodontid salamanders reveal them to be an
      old radiation whose common ancestor diverged from sister taxa in the late
      Jurassic and underwent rapid diversification during the late Cretaceous. A North
      American origin of plethodontids was followed by a continental-wide
      diversification, not necessarily centered only in the Appalachian region. The
      colonization of Eurasia by plethodontids most likely occurred once, by dispersal
      during the late Cretaceous. Subsequent diversification in Asia led to the origin
      of Hydromantes and Karsenia, with the former then dispersing both to Europe and
      back to North America. Salamanders underwent rapid episodes of diversification
      and dispersal that coincided with major global warming events during the late
      Cretaceous and again during the Paleocene-Eocene thermal optimum. The major
      clades of plethodontids were established during these episodes, contemporaneously
      with similar phenomena in angiosperms, arthropods, birds, and mammals. Periods of
      global warming may have promoted diversification and both inter- and
      transcontinental dispersal in northern hemisphere salamanders by making available
      terrain that shortened dispersal routes and offered new opportunities for
      adaptive and vicariant evolution.

PMID- 18077423
TI  - Nucleomorph genome of Hemiselmis andersenii reveals complete intron loss and
      compaction as a driver of protein structure and function.
AB  - Nucleomorphs are the remnant nuclei of algal endosymbionts that took up residence
      inside a nonphotosynthetic eukaryotic host. The nucleomorphs of cryptophytes and
      chlorarachniophytes are derived from red and green algal endosymbionts,
      respectively, and represent a stunning example of convergent evolution: their
      genomes have independently been reduced and compacted to <1 megabase pairs (Mbp)
      in size (the smallest nuclear genomes known) and to a similar three-chromosome
      architecture. The molecular processes underlying genome reduction and compaction
      in eukaryotes are largely unknown, as is the impact of reduction/compaction on
      protein structure and function. Here, we present the complete 0.572-Mbp
      nucleomorph genome of the cryptophyte Hemiselmis andersenii and show that it is
      completely devoid of spliceosomal introns and genes for splicing RNAs-a case of
      complete intron loss in a nuclear genome. Comparison of H. andersenii proteins to
      those encoded in the slightly smaller (0.551-Mbp) nucleomorph genome of another
      cryptophyte, Guillardia theta, and to their homologs in the unicellular red alga
      Cyanidioschyzon merolae reveal that (i) cryptophyte nucleomorph genomes encode
      proteins that are significantly smaller than those in their free-living algal
      ancestors, and (ii) the smaller, more compact G. theta nucleomorph genome encodes
      significantly smaller proteins than that of H. andersenii. These results indicate
      that genome compaction can eliminate both coding and noncoding DNA and,
      consequently, drive the evolution of protein structure and function. Nucleomorph
      proteins have the potential to reveal the minimal functional units required for
      basic eukaryotic cellular processes.

PMID- 18077424
TI  - Input output robustness in simple bacterial signaling systems.
AB  - Biological signaling systems produce an output, such as the level of a
      phosphorylated protein, in response to defined input signals. The output level as
      a function of the input level is called the system's input-output relation. One
      may ask whether this input-output relation is sensitive to changes in the
      concentrations of the system's components, such as proteins and ATP. Because
      component concentrations often vary from cell to cell, it might be expected that
      the input-output relation will likewise vary. If this is the case, different
      cells exposed to the same input signal will display different outputs. Such
      variability can be deleterious in systems where survival depends on accurate
      match of output to input. Here we suggest a mechanism that can provide input
      output robustness, that is, an input-output relation that does not depend on
      variations in the concentrations of any of the system's components. The mechanism
      is based on certain bacterial signaling systems. It explains how specific
      molecular details can work together to provide robustness. Moreover, it suggests
      an approach that can help identify a wide family of nonequilibrium mechanisms
      that potentially have robust input-output relations.

PMID- 18077425
TI  - Identification of genotype-correlated sensitivity to selective kinase inhibitors
      by using high-throughput tumor cell line profiling.
AB  - Kinase inhibitors constitute an important new class of cancer drugs, whose
      selective efficacy is largely determined by underlying tumor cell genetics. We
      established a high-throughput platform to profile 500 cell lines derived from
      diverse epithelial cancers for sensitivity to 14 kinase inhibitors. Most
      inhibitors were ineffective against unselected cell lines but exhibited dramatic
      cell killing of small nonoverlapping subsets. Cells with exquisite sensitivity to
      EGFR, HER2, MET, or BRAF kinase inhibitors were marked by activating mutations or
      amplification of the drug target. Although most cell lines recapitulated known
      tumor-associated genotypes, the screen revealed low-frequency drug-sensitizing
      genotypes in tumor types not previously associated with drug susceptibility.
      Furthermore, comparing drugs thought to target the same kinase revealed striking
      differences, predictive of clinical efficacy. Genetically defined cancer subsets,
      irrespective of tissue type, predict response to kinase inhibitors, and provide
      an important preclinical model to guide early clinical applications of novel
      targeted inhibitors.

PMID- 18077426
TI  - Runs of homozygosity reveal highly penetrant recessive loci in schizophrenia.
AB  - Evolutionarily significant selective sweeps may result in long stretches of
      homozygous polymorphisms in individuals from outbred populations. We developed
      whole-genome homozygosity association (WGHA) methodology to characterize this
      phenomenon in healthy individuals and to use this genomic feature to identify
      genetic risk loci for schizophrenia (SCZ). Applying WGHA to 178 SCZ cases and 144
      healthy controls genotyped at 500,000 markers, we found that runs of homozygosity
      (ROHs), ranging in size from 200 kb to 15 mb, were common in unrelated
      Caucasians. Properties of common ROHs in healthy subjects, including chromosomal
      location and presence of nonancestral haplotypes, converged with prior reports
      identifying regions under selective pressure. This interpretation was further
      supported by analysis of multiethnic HapMap samples genotyped with the same
      markers. ROHs were significantly more common in SCZ cases, and a set of nine ROHs
      significantly differentiated cases from controls. Four of these 9 "risk ROHs"
      contained or neighbored genes associated with SCZ (NOS1AP, ATF2, NSF, and
      PIK3C3). Several of these risk ROHs were very rare in healthy subjects,
      suggesting that recessive effects of relatively high penetrance may explain a
      proportion of the genetic liability for SCZ. Other risk ROHs feature haplotypes
      that are also common in healthy individuals, possibly indicating a source of
      balancing selection.

PMID- 18077427
TI  - Protein characterization of Saccharomyces cerevisiae RNA polymerase II after in
      vivo cross-linking.
AB  - To characterize proteins associated with active transcription complexes, we
      purified RNA polymerase II (pol II) from Saccharomyces cerevisiae after fixing
      live cells with formaldehyde. The approach mimics ChIP and requires solubilizing
      cross-linked complexes with sonication. Pol II was affinity-purified, and
      associated proteins were identified by MS. Several classes of proteins depended
      on cross-linking, including Mediator, general transcription factors, elongation
      factors, ribonucleoprotein particle (RNP) proteins, and histones. A tagged RNP
      protein reciprocally purified pol II under identical cross-linking conditions,
      and the association between RNP proteins and pol II was largely RNase-sensitive.
      The data indicate that the cross-linked Pol II purification contains elongating
      pol II with associated nascent RNP. Consistent with this view, some elongation
      factors no longer associate with pol II after inactivation of transcription in
      the temperature-sensitive pol II mutant, rpb1-1. Taken together, our data suggest
      that the cross-linked pol II purification contains a mixed population of pol II,
      including initiating pol II and elongating pol II.

PMID- 18077428
TI  - Protective effect of noninherited maternal HLA-DR antigens on rheumatoid
      arthritis development.
AB  - Rheumatoid arthritis (RA) is a complex genetic disorder in which the HLA-region
      contributes most to the genetic risk. HLA-DRB1-molecules containing the amino
      acid sequence DERAA (i.e., HLA-DRB1*0103, *0402, *1102, *1103, *1301, *1302, and
      *1304) are associated with protection from RA. It has been proposed that not only
      inherited but also noninherited HLA-antigens from the mother (NIMA) can influence
      RA-susceptibility. Up to now, no protective NIMAs were described. Here, we
      studied whether DERAA-containing HLA-DRB1-alleles as NIMA are associated with a
      protective effect. One hundred seventy-nine families were studied, 88 from the
      Netherlands and 91 from the United Kingdom. The frequency of DERAA-containing HLA
      DRB1-alleles of the Dutch mothers (16.1%), but not of the fathers (26.2%), was
      lower compared with the general Dutch population (29.3%; P = 0.02). This was
      replicated in the English set of patients and controls (P = 0.01). Further, of
      all families, 45 contained at least one DERAA-negative child with RA and at least
      one DERAA-positive parent. The odds for the DERAA-negative RA patients of having
      a DERAA-positive mother was significantly lower compared with having a DERAA
      positive father (OR 0.25; P = 0.003). These data show a protective NIMA-effect in
      a human autoimmune disease and indicate that a DERAA-positive mother can transfer
      protection against RA to her DERAA-negative child.

PMID- 18077429
TI  - Mast cells are an essential hematopoietic component for polyp development.
AB  - It is generally agreed that most colon cancers develop from adenomatous polyps,
      and it is this fact on which screening strategies are based. Although there is
      overwhelming evidence to link intrinsic genetic lesions with the formation of
      these preneoplastic lesions, recent data suggest that the tumor stromal
      environment also plays an essential role in this disease. In particular, it has
      been suggested that CD34(+) immature myeloid precursor cells are required for
      tumor development and invasion. Here we have used mice conditional for the
      stabilization of beta-catenin or defective for the adenomatous polyposis coli
      (APC) gene to reinvestigated the identity and importance of tumor-infiltrating
      hematopoietic cells in polyposis. We show that, from the onset, polyps are
      infiltrated with proinflammatory mast cells (MC) and their precursors. Depletion
      of MC either pharmacologically or through the generation of chimeric mice with
      genetic lesions in MC development leads to a profound remission of existing
      polyps. Our data suggest that MC are an essential hematopoietic component for
      preneoplastic polyp development and are a novel target for therapeutic
      intervention.

PMID- 18077430
TI  - Effects of rearrangement and allelic exclusion of JJAZ1/SUZ12 on cell
      proliferation and survival.
AB  - Polycomb group genes (PcGs) have been implicated in cancer based on altered
      levels of expression observed in certain tumors and the behavior of cultured
      cells containing inserted PcG transgenes. Endometrial stromal tumors provide
      evidence for a direct causal relationship because they contain several
      chromosomal translocations and resultant gene fusions involving PcGs, the most
      common of which joins portions of the JAZF1 gene to the PcGJJAZ1/SUZ12. We show
      here that both benign and malignant forms of this tumor have the JAZF1-JJAZ1
      fusion but only the malignant form also exhibits exclusion of the unrearranged
      JJAZ1 allele. To evaluate the effects of both the JJAZ1/SUZ12 fusion and allelic
      exclusion on functions related to cell growth, we studied HEK293 cells that were
      modified with respect to JJAZ1 expression. We found that the JAZF1-JJAZ1 fusion
      restored levels of the polycomb protein EZH2 and histone 3 lysine 27
      trimethylation, which were reduced by knockdown of endogenous JJAZ1. At the same
      time, the presence of JAZF1-JJAZ1 markedly inhibited apoptosis and induced above
      normal proliferation rates, although the latter effect occurred only when normal
      JJAZ1 was suppressed. Our findings suggest a genetic pathway for progression of a
      benign precursor to a sarcoma involving increased cell survival associated with
      acquisition of a PcG rearrangement, followed by accelerated cellular
      proliferation upon allelic exclusion of the unrearranged copy of that gene.
      Furthermore, these results indicate the likely functional importance of allelic
      exclusion of genes disrupted by chromosomal translocations, as seen in a variety
      of other cancers.

PMID- 18077431
TI  - Assessing the significance of chromosomal aberrations in cancer: methodology and
      application to glioma.
AB  - Comprehensive knowledge of the genomic alterations that underlie cancer is a
      critical foundation for diagnostics, prognostics, and targeted therapeutics.
      Systematic efforts to analyze cancer genomes are underway, but the analysis is
      hampered by the lack of a statistical framework to distinguish meaningful events
      from random background aberrations. Here we describe a systematic method, called
      Genomic Identification of Significant Targets in Cancer (GISTIC), designed for
      analyzing chromosomal aberrations in cancer. We use it to study chromosomal
      aberrations in 141 gliomas and compare the results with two prior studies.
      Traditional methods highlight hundreds of altered regions with little concordance
      between studies. The new approach reveals a highly concordant picture involving
      approximately 35 significant events, including 16-18 broad events near chromosome
      arm size and 16-21 focal events. Approximately half of these events correspond to
      known cancer-related genes, only some of which have been previously tied to
      glioma. We also show that superimposed broad and focal events may have different
      biological consequences. Specifically, gliomas with broad amplification of
      chromosome 7 have properties different from those with overlapping focalEGFR
      amplification: the broad events act in part through effects on MET and its ligand
      HGF and correlate with MET dependence in vitro. Our results support the
      feasibility and utility of systematic characterization of the cancer genome.

PMID- 18077433
TI  - Deletion of the core-H region in mice abolishes the expression of three proximal
      odorant receptor genes in cis.
AB  - We have previously reported that a 2.1-kb homology (H) sequence, conserved
      between mouse and human, regulates the odorant receptor (OR) gene MOR28 in
      transgenic mice. Here, we narrowed down the essential sequences of the H to a
      core of 124 bp by using a transient expression system in zebrafish embryos.
      Transgenic experiments in mice demonstrated that the core-H sequence is
      sufficient to endow expression of the MOR28 minigene. Deletion and mutation
      analyses of the core-H region revealed two homeodomain sequences to be essential
      for the H enhancer activity. Targeted deletion of the core-H abolished expression
      of three proximal OR genes, MOR28, MOR10, and MOR83, in cis, indicating the
      presence of another locus control region/enhancer in the downstream region, that
      regulates four distal OR genes in the same MOR28 cluster. In the heterozygous
      mice, the H(-) phenotype of the mutant allele was not rescued by the wild-type
      H(+) allele in trans.

PMID- 18077432
TI  - Human cytomegalovirus uses two distinct pathways to enter retinal pigmented
      epithelial cells.
AB  - Human cytomegalovirus infects multiple cell types, including fibroblasts and
      epithelial cells. It penetrates fibroblasts by fusion at the cell surface but is
      endocytosed into epithelial cells. In this report, we demonstrate by electron
      microscopy that the virus uses two different routes to enter retinal pigmented
      epithelial cells, depending on the cell type in which the infecting virus was
      produced. Virus produced in epithelial cells preferentially fuses with the plasma
      membrane, whereas fibroblast-derived virus mostly enters by receptor-mediated
      endocytosis. Treatment of epithelial cells with agents that block endosome
      acidification inhibited infection by virus produced in fibroblasts but had only a
      modest effect on infection by virus from epithelial cells. Epithelial cell
      generated virions had higher intrinsic "fusion-from-without" activity than
      fibroblast-generated particles, and the two virus preparations triggered
      different cellular signaling responses, as evidenced by markedly different
      transcriptional profiles. We propose that the cell type in which a human
      cytomegalovirus particle is produced likely influences its subsequent spread and
      its contribution to pathogenesis.

PMID- 18077434
TI  - Perceptual detection as a dynamical bistability phenomenon: a neurocomputational
      correlate of sensation.
AB  - Recent studies that combined psychophysical/neurophysiological experiments [de
      Lafuente V, Romo R (2005) Nat Neurosci 8:1698-1703] analyzed the responses from
      single neurons, recorded in several cortical areas of parietal and frontal lobes,
      while trained monkeys reported the presence or absence of a mechanical vibration
      of varying amplitude applied to skin of one fingertip. The analysis showed that
      the activity of primary somatosensory cortex neurons covaried with the stimulus
      strength but did not covary with the animal's perceptual reports. In contrast,
      the activity of medial premotor cortex (MPC) neurons did not covary with the
      stimulus strength but did covary with the animal's perceptual reports. Here, we
      address the question of how perceptual detection is computed in MPC. In
      particular, we regard perceptual detection as a bistable neurodynamical
      phenomenon reflected in the activity of MPC. We show that the activity of MPC is
      consistent with a decision-making-like scenario of fluctuation-driven computation
      that causes a probabilistic transition between two bistable states, one
      corresponding to the case in which the monkey detects the sensory input, the
      other corresponding to the case in which the monkey does not. Moreover, the high
      variability activity of MPC neurons both within and between trials reflects
      stochastic fluctuations that may play a crucial role in the monkey's
      probabilistic perceptual reports.

PMID- 18077435
TI  - Homer1a is a core brain molecular correlate of sleep loss.
AB  - Sleep is regulated by a homeostatic process that determines its need and by a
      circadian process that determines its timing. By using sleep deprivation and
      transcriptome profiling in inbred mouse strains, we show that genetic background
      affects susceptibility to sleep loss at the transcriptional level in a tissue
      dependent manner. In the brain, Homer1a expression best reflects the response to
      sleep loss. Time-course gene expression analysis suggests that 2,032 brain
      transcripts are under circadian control. However, only 391 remain rhythmic when
      mice are sleep-deprived at four time points around the clock, suggesting that
      most diurnal changes in gene transcription are, in fact, sleep-wake-dependent. By
      generating a transgenic mouse line, we show that in Homer1-expressing cells
      specifically, apart from Homer1a, three other activity-induced genes (Ptgs2,
      Jph3, and Nptx2) are overexpressed after sleep loss. All four genes play a role
      in recovery from glutamate-induced neuronal hyperactivity. The consistent
      activation of Homer1a suggests a role for sleep in intracellular calcium
      homeostasis for protecting and recovering from the neuronal activation imposed by
      wakefulness.

PMID- 18077436
TI  - Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum
      protein JP45.
AB  - Skeletal muscle constitutes approximately 40% of the human body mass, and
      alterations in muscle mass and strength may result in physical disability.
      Therefore, the elucidation of the factors responsible for muscle force
      development is of paramount importance. Excitation-contraction coupling (ECC) is
      a process during which the skeletal muscle surface membrane is depolarized,
      causing a transient release of calcium from the sarcoplasmic reticulum that
      activates the contractile proteins. The ECC machinery is complex, and the
      functional role of many of its protein components remains elusive. This study
      demonstrates that deletion of the gene encoding the sarcoplasmic reticulum
      protein JP45 results in decreased muscle strength in young mice. Specifically,
      this loss of muscle strength in JP45 knockout mice is caused by decreased
      functional expression of the voltage-dependent Ca(2+) channel Ca(v)1.1, which is
      the molecule that couples membrane depolarization and calcium release from the
      sarcoplasmic reticulum. These results point to JP45 as one of the molecules
      involved in the development or maintenance of skeletal muscle strength.

PMID- 18077437
TI  - Skeletal muscle resists stretch by rapid binding of the second motor domain of
      myosin to actin.
AB  - A shortening muscle is a machine that converts metabolic energy into mechanical
      work, but, when a muscle is stretched, it acts as a brake, generating a high
      resistive force at low metabolic cost. The braking action of muscle can be
      activated with remarkable speed, as when the leg extensor muscles rapidly
      decelerate the body at the end of a jump. Here we used time-resolved x-ray and
      mechanical measurements on isolated muscle cells to elucidate the molecular basis
      of muscle braking and its rapid control. We show that a stretch of only 5 nm
      between each overlapping set of myosin and actin filaments in a muscle sarcomere
      is sufficient to double the number of myosin motors attached to actin within a
      few milliseconds. Each myosin molecule has two motor domains, only one of which
      is attached to actin during shortening or activation at constant length. A
      stretch strains the attached motor domain, and we propose that combined steric
      and mechanical coupling between the two domains promotes attachment of the second
      motor domain. This mechanism allows skeletal muscle to resist external stretch
      without increasing the force per motor and provides an answer to the longstanding
      question of the functional role of the dimeric structure of muscle myosin.

PMID- 18077438
TI  - Phorbol ester stimulation of RasGRP1 regulates the sodium-chloride cotransporter
      by a PKC-independent pathway.
AB  - The sodium-chloride cotransporter (NCC) is the principal salt-absorptive pathway
      in the mammalian distal convoluted tubule (DCT) and is the site of action of one
      of the most effective classes of antihypertensive medications, thiazide
      diuretics. We developed a cell model system to assess NCC function in a mammalian
      cell line that natively expresses NCC, the mouse DCT (mDCT) cell line. We used
      this system to study the complex regulation of NCC by the phorbol ester (PE) 12-O
      tetradecanoylphorbol-13-acetate (TPA), a diacylglycerol (DAG) analog. It has
      generally been thought that PEs mediate their effects on transporters through the
      activation of PKC. However, there are at least five other DAG/PE targets. Here we
      describe how one of those alternate targets of DAG/PE effects, Ras guanyl
      releasing protein 1 (RasGRP1), mediates the PE-induced suppression of function
      and the surface expression of NCC. Functional assessment of NCC by using thiazide
      sensitive (22)Na(+) uptakes revealed that TPA completely suppresses NCC function.
      Biotinylation experiments demonstrated that this result was primarily because of
      decreased surface expression of NCC. Although inhibitors of PKC had no effect on
      this suppression, MAPK inhibitors completely prevented the TPA effect. RasGRP1
      activates the MAPK pathway through activation of the small G protein Ras. Gene
      silencing of RasGRP1 prevented the PE-mediated suppression of NCC activity, the
      activation of the H-Ras isoform of Ras, and the activation of ERK1/2 MAPK. This
      finding confirmed the critical role of RasGRP1 in mediating the PE-induced
      suppression of NCC activity through the stimulation of the MAPK pathway.

PMID- 18077439
TI  - A high-affinity molybdate transporter in eukaryotes.
AB  - Molybdenum is an essential element for almost all living beings, which, in the
      form of a molybdopterin-cofactor, participates in the active site of enzymes
      involved in key reactions of carbon, nitrogen, and sulfur metabolism. This metal
      is taken up by cells in form of the oxyanion molybdate. Bacteria acquire
      molybdate by an ATP-binding-cassette (ABC) transport system in a widely studied
      process, but how eukaryotic cells take up molybdenum is unknown because molybdate
      transporters have not been identified so far. Here, we report a eukaryotic high
      affinity molybdate transporter, encoded by the green alga Chlamydomonas
      reinhardtii gene MoT1. An antisense RNA strategy over the MoT1 gene showed that
      interference of the expression of this gene leads to the inhibition of molybdate
      transport activity and, in turn, of the Mo-containing enzyme nitrate reductase,
      indicating a function of MoT1 in molybdate transport. MOT1 functionality was also
      shown by heterologous expression in Saccharomyces cerevisiae. Molybdate uptake
      mediated by MOT1 showed a K(m) of approximately 6 nM, which is the range of the
      lowest K(m) values reported and was activated in the presence of nitrate.
      Analysis of deduced sequence from the putative protein coded by MoT1 showed
      motifs specifically conserved in similar proteins present in the databases, and
      defines a family of membrane proteins in both eukaryotes and prokaryotes probably
      involved in molybdate transport and distantly related to plant sulfate
      transporters SULTR. These findings represent an important step in the
      understanding of molybdate transport, a crucial process in eukaryotic cells.

PMID- 18077440
TI  - Risk of respiratory morbidity in term infants delivered by elective caesarean
      section: cohort study.
AB  - OBJECTIVE: To investigate the association between elective caesarean sections and
      neonatal respiratory morbidity and the importance of timing of elective caesarean
      sections. DESIGN: Cohort study with prospectively collected data from the Aarhus
      birth cohort, Denmark. SETTING: Obstetric department and neonatal department of a
      university hospital in Denmark. PARTICIPANTS: All liveborn babies without
      malformations, with gestational ages between 37 and 41 weeks, and delivered
      between 1 January 1998 and 31 December 2006 (34 458 babies). MAIN OUTCOME
      MEASURES: Respiratory morbidity (transitory tachypnoea of the newborn,
      respiratory distress syndrome, persistent pulmonary hypertension of the newborn)
      and serious respiratory morbidity (oxygen therapy for more than two days, nasal
      continuous positive airway pressure, or need for mechanical ventilation).
      RESULTS: 2687 infants were delivered by elective caesarean section. Compared with
      newborns intended for vaginal delivery, an increased risk of respiratory
      morbidity was found for infants delivered by elective caesarean section at 37
      weeks' gestation (odds ratio 3.9, 95% confidence interval 2.4 to 6.5), 38 weeks'
      gestation (3.0, 2.1 to 4.3), and 39 weeks' gestation (1.9, 1.2 to 3.0). The
      increased risks of serious respiratory morbidity showed the same pattern but with
      higher odds ratios: a fivefold increase was found at 37 weeks (5.0, 1.6 to16.0).
      These results remained essentially unchanged after exclusion of pregnancies
      complicated by diabetes, pre-eclampsia, and intrauterine growth retardation, or
      by breech presentation. CONCLUSION: Compared with newborns delivered vaginally or
      by emergency caesarean sections, those delivered by elective caesarean section
      around term have an increased risk of overall and serious respiratory morbidity.
      The relative risk increased with decreasing gestational age.

PMID- 18077441
TI  - Chronic atrial fibrillation ablation impact on endocrine and mechanical cardiac
      functions.
AB  - AIMS: Assess the impact of persistent/permanent atrial fibrillation (AF) ablation
      on endocrine and mechanical cardiac functions. METHODS AND RESULTS: In all, 43
      patients (40 males, 53 +/- 12 years) undergoing persistent/permanent AF ablation
      had atrial (ANP) and brain natriuretic peptide (BNP) measurements before day 1,
      3, and 3 months after ablation. In the same period of time transthoracic
      echocardiography was performed. With a mean radiofrequency delivery of 98 +/- 29
      min, sinus rhythm (SR) was restored in 30 patients (70%) without DC shock. ANP
      decreased significantly (P < 0.001) with restoration of SR and then increased
      until day 3 post ablation without reaching the level observed during AF. At 3
      months, ANP was significantly lower than day 3 reaching normal value in 28 (65%)
      patients and being <7 pg/mL in 4 (9%). The BNP followed the same trend with
      normal BNP level in 23 (53%) patients at 3 months. Identifiable atrial filling
      waves on the pulsed Doppler transmitral recordings performed between day 2 and
      day 4 after the procedure were seen in 18 patients (42%). At 3 months, 39 (95%)
      of the patients with SR during echocardiography had a significant A wave.
      CONCLUSION: SR following persistent/permanent AF ablation is associated with a
      dramatic decrease in natriuretic peptides. At 3 months, despite relatively
      extensive atrial ablation, endocrine and mechanical cardiac functions are
      significantly improved.

PMID- 18077442
TI  - Contribution of organized thrombus to in-stent restenosis after sirolimus-eluting
      stent implantation: optical coherence tomography findings.

PMID- 18077443
TI  - Humoral response profiling reveals pathways to prostate cancer progression.
AB  - There is considerable evidence for an association between prostate cancer
      development and inflammation, which results in autoantibody generation against
      tumor proteins. This immune system-driven amplification of the autoantibody
      response to intracellular antigens can serve as a sensitive tool to detect low
      abundance serum proteomic tumor markers for prostate cancer as well as provide
      insight into biological processes perturbed during cancer development. Here we
      examine serum humoral responses in a cohort of 34 patients with either benign
      prostatic hyperplasia or clinically localized prostate cancer (PCa). The
      experimental strategy couples multidimensional liquid-phase protein fractionation
      of localized and metastatic prostate cancer tissue lysates to protein microarrays
      and subsequent mass spectrometry. A supervised learning analysis of the humoral
      response arrays generated a parsimonious predictor having 78% sensitivity and 75%
      specificity in distinguishing PCa from benign prostatic hyperplasia in a cohort
      of American males with elevated prostate-specific antigen. Enrichment analysis of
      the PCa-specific humoral signature revealed large scale immune reprogramming
      mediated by STAT transcription factors and the generation of autoantibodies to
      enzymes involved in nitrogen metabolism. Meta-analysis of independent prostate
      cancer gene expression data validated the presence of STAT-induced
      immunomodulation. Concomitant validation of elevated levels of the nitrogen
      metabolism pathway was obtained by direct measurement of metabolic levels of
      glutamate and aspartate in prostate cancer tissues. Thus, in addition to
      functioning as markers in prostate cancer detection, humoral response profiles
      can serve as powerful tools revealing pathway dysregulation that might otherwise
      be suppressed by the complexity of the cancer proteome.

PMID- 18077444
TI  - Hyaluronan-CD44-ERK1/2 regulate human aortic smooth muscle cell motility during
      aging.
AB  - The glycosaminoglycan hyaluronan (HA) modulates cell proliferation and migration,
      and it is involved in several human vascular pathologies including
      atherosclerosis and vascular restenosis. During intima layer thickening, HA
      increases dramatically in the neointima extracellular matrix. Aging is one of the
      major risk factors for the insurgence of vascular diseases, in which smooth
      muscle cells (SMCs) play a role by determining neointima formation through their
      migration and proliferation. Therefore, we established an in vitro aging model
      consisting of sequential passages of human aortic smooth muscle cells (AoSMCs).
      Comparing young and aged cells, we found that, during the aging process in
      vitro,HA synthesis significantly increases, as do HA synthetic enzymes (i.e. HAS2
      and HAS3), the precursor synthetic enzyme (UDP-glucose dehydrogenase), and the HA
      receptor CD44. In aged cells, we also observed increased CD44 signaling that
      consisted of higher levels of phosphorylated MAP kinase ERK1/2. Further, aged
      AoSMCs migrated faster than young cells, and such migration could be modulated by
      HA, which alters the ERK1/2 phosphorylation. HA oligosaccharides of 6.8 kDa and
      an anti-CD44 blocking antibody prevented ERK1/2 phosphorylation and inhibited
      AoSMCs migration. These results indicate that, during aging, HA can modulate cell
      migration involving CD44-mediated signaling through ERK1/2. These data suggest
      that age-related HA accumulation could promote SMC migration and intima
      thickening during vascular neointima formation.

PMID- 18077445
TI  - Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1.
AB  - The NKX3.1 gene located at 8p21.2 encodes a homeodomain-containing transcription
      factor that acts as a haploinsufficient tumor suppressor in prostate cancer.
      Diminished protein expression of NKX3.1 has been observed in prostate cancer
      precursors and carcinomas. TOPORS is a ubiquitously expressed E3 ubiquitin ligase
      that can ubiquitinate tumor suppressor p53. Here we report interaction between
      NKX3.1 and TOPORS. NKX3.1 can be ubiquitinated by TOPORS in vitro and in vivo,
      and overexpression of TOPORS leads to NKX3.1 proteasomal degradation in prostate
      cancer cells. Conversely, small interfering RNA-mediated knockdown of TOPORS
      leads to an increased steady-state level and prolonged half-life of NKX3.1. These
      data establish TOPORS as a negative regulator of NKX3.1 and implicate TOPORS in
      prostate cancer progression.

PMID- 18077446
TI  - AICAR induces astroglial differentiation of neural stem cells via activating the
      JAK/STAT3 pathway independently of AMP-activated protein kinase.
AB  - Neural stem cell differentiation and the determination of lineage decision
      between neuronal and glial fates have important implications in the study of
      developmental, pathological, and regenerative processes. Although small molecule
      chemicals with the ability to control neural stem cell fate are considered
      extremely useful tools in this field, few were reported. AICAR is an adenosine
      analog and extensively used to activate AMP-activated protein kinase (AMPK), a
      metabolic "fuel gauge" of the biological system. In the present study, we found
      an unrecognized astrogliogenic activity of AICAR on not only immortalized neural
      stem cell line C17.2 (C17.2-NSC), but also primary neural stem cells (NSCs)
      derived from post-natal (P0) rat hippocampus (P0-NSC) and embryonic day 14 (E14)
      rat embryonic cortex (E14-NSC). However, another AMPK activator, Metformin, did
      not alter either the C17.2-NSC or E14-NSC undifferentiated state although both
      Metformin and AICAR can activate the AMPK pathway in NSC. Furthermore,
      overexpression of dominant-negative mutants of AMPK in C17.2-NSC was unable to
      block the gliogenic effects of AICAR. We also found AICAR could activate the
      Janus kinase (JAK) STAT3 pathway in both C17.2-NSC and E14-NSC but Metformin
      fails. JAK inhibitor I abolished the gliogenic effects of AICAR. Taken together,
      these results suggest that the astroglial differentiation effect of AICAR on
      neural stem cells was acting independently of AMPK and that the JAK-STAT3 pathway
      is essential for the gliogenic effect of AICAR.

PMID- 18077447
TI  - Structural basis for accelerated cleavage of bovine pancreatic trypsin inhibitor
      (BPTI) by human mesotrypsin.
AB  - Human mesotrypsin is an isoform of trypsin that displays unusual resistance to
      polypeptide trypsin inhibitors and has been observed to cleave several such
      inhibitors as substrates. Whereas substitution of arginine for the highly
      conserved glycine 193 in the trypsin active site has been implicated as a
      critical factor in the inhibitor resistance of mesotrypsin, how this substitution
      leads to accelerated inhibitor cleavage is not clear. Bovine pancreatic trypsin
      inhibitor (BPTI) forms an extremely stable and cleavage-resistant complex with
      trypsin, and thus provides a rigorous challenge of mesotrypsin catalytic activity
      toward polypeptide inhibitors. Here, we report kinetic constants for mesotrypsin
      and the highly homologous (but inhibitor sensitive) human cationic trypsin,
      describing inhibition by, and cleavage of BPTI, as well as crystal structures of
      the mesotrypsin-BPTI and human cationic trypsin-BPTI complexes. We find that
      mesotrypsin cleaves BPTI with a rate constant accelerated 350-fold over that of
      human cationic trypsin and 150,000-fold over that of bovine trypsin. From the
      crystal structures, we see that small conformational adjustments limited to
      several side chains enable mesotrypsin-BPTI complex formation, surmounting the
      predicted steric clash introduced by Arg-193. Our results show that the
      mesotrypsin-BPTI interface favors catalysis through (a) electrostatic repulsion
      between the closely spaced mesotrypsin Arg-193 and BPTI Arg-17, and (b)
      elimination of two hydrogen bonds between the enzyme and the amine leaving group
      portion of BPTI. Our model predicts that these deleterious interactions
      accelerate leaving group dissociation and deacylation.

PMID- 18077448
TI  - Characterization of tRNA-dependent peptide bond formation by MurM in the
      synthesis of Streptococcus pneumoniae peptidoglycan.
AB  - MurM is an aminoacyl ligase that adds l-serine or l-alanine as the first amino
      acid of a dipeptide branch to the stem peptide lysine of the pneumococcal
      peptidoglycan. MurM activity is essential for clinical pneumococcal penicillin
      resistance. Analysis of peptidoglycan from the highly penicillin-resistant
      Streptococcus pneumoniae strain 159 revealed that in vivo and in vitro, in the
      presence of the appropriate acyl-tRNA, MurM(159) alanylated the peptidoglycan
      epsilon-amino group of the stem peptide lysine in preference to its serylation.
      However, in contrast, identical analyses of the penicillin-susceptible strain
      Pn16 revealed that MurM(Pn16) activity supported serylation more than alanylation
      both in vivo and in vitro. Interestingly, both MurM(Pn16) acylation activities
      were far lower than the alanylation activity of MurM(159). The resulting
      differing stem peptide structures of 159 and Pn16 were caused by the profoundly
      greater catalytic efficiency of MurM(159) compared with MurM(Pn16) bought about
      by sequence variation between these enzymes and, to a lesser extent, differences
      in the in vivo tRNA(Ala):tRNA(Ser) ratio in 159 and Pn16. Kinetic analysis
      revealed that MurM(159) acted during the lipid-linked stages of peptidoglycan
      synthesis, that the d-alanyl-d-alanine of the stem peptide and the lipid II N
      acetylglucosaminyl group were not essential for substrate recognition, that
      epsilon-carboxylation of the lysine of the stem peptide was not tolerated, and
      that lipid II-alanine was a substrate, suggesting an evolutionary link to
      staphylococcal homologues of MurM such as FemA. Kinetic analysis also revealed
      that MurM recognized the acceptor stem and/or the TPsiC loop stem of the
      tRNA(Ala). It is anticipated that definition of the minimal structural features
      of MurM substrates will allow development of novel resistance inhibitors that
      will restore the efficacy of beta-lactams for treatment of pneumococcal
      infection.

PMID- 18077449
TI  - Hypoxia promotes the differentiated human articular chondrocyte phenotype through
      SOX9-dependent and -independent pathways.
AB  - The chondrocyte is solely responsible for synthesis and maintenance of the
      resilient articular cartilage matrix that gives this load-bearing tissue its
      mechanical integrity. When the differentiated cell phenotype is lost, the matrix
      becomes compromised and cartilage function begins to fail. We have recently shown
      that hypoxia promotes the differentiated phenotype through hypoxia-inducible
      factor 2alpha (HIF-2alpha)-mediated SOX9 induction of the main matrix genes.
      However, to date, only a few genes have been shown to be SOX9 targets, while
      little is known about SOX9-independent regulators. We therefore performed a
      detailed microarray study to address these issues. Analysis involved 35 arrays on
      chondrocytes obtained from seven healthy, non-elderly human cartilage samples.
      Genes were selected that were down-regulated with serial passage in culture (as
      this causes loss of the differentiated phenotype) and subsequently up-regulated
      in hypoxia. The importance of key findings was further probed using the technique
      of RNA interference on these human articular chondrocytes. Our results show that
      hypoxia has a broader beneficial effect on the chondrocyte phenotype than has
      been previously described. Of special note, we report new hypoxia-inducible and
      SOX9-regulated genes, Gdf10 and Chm-I. In addition, Mig6 and InhbA were induced
      by hypoxia, predominantly via HIF-2alpha, but were not regulated by SOX9.
      Therefore, hypoxia, and more specifically HIF-2alpha, promotes both SOX9
      dependent and -independent factors important for cartilage homeostasis. HIF
      2alpha may therefore represent a new and promising therapeutic target for
      cartilage repair.

PMID- 18077451
TI  - Recycling of dolichyl monophosphate to the cytoplasmic leaflet of the endoplasmic
      reticulum after the cleavage of dolichyl pyrophosphate on the lumenal monolayer.
AB  - During protein N-glycosylation, dolichyl pyrophosphate (Dol-P-P) is discharged in
      the lumenal monolayer of the endoplasmic reticulum (ER). Dol-P-P is then cleaved
      to Dol-P by Dol-P-P phosphatase (DPPase). Studies with the yeast mutant
      cwh8Delta, lacking DPPase activity, indicate that recycling of Dol-P produced by
      DPPase contributes significantly to the pool of Dol-P utilized for lipid
      intermediate biosynthesis on the cytoplasmic leaflet. Whether Dol-P formed in the
      lumen diffuses directly back to the cytoplasmic leaflet or is first
      dephosphorylated to dolichol has not been determined. Incubation of sealed ER
      vesicles from calf brain with acetyl-Asn-Tyr-Thr-NH(2), an N-glycosylatable
      peptide, to generate Dol-P-P in the lumenal monolayer produced corresponding
      increases in the rates of Man-P-Dol, Glc-P-Dol, and GlcNAc-P-P-Dol synthesis in
      the absence of CTP. No changes in dolichol kinase activity were observed. When
      streptolysin-O permeabilized CHO cells were incubated with an acceptor peptide, N
      glycopeptide synthesis, requiring multiple cycles of the dolichol pathway,
      occurred in the absence of CTP. The results obtained with sealed microsomes and
      CHO cells indicate that Dol-P, formed from Dol-P-P, returns to the cytoplasmic
      leaflet where it can be reutilized for lipid intermediate biosynthesis, and
      dolichol kinase is not required for recycling. It is possible that the flip
      flopping of the carrier lipid is mediated by a flippase, which would provide a
      mechanism for the recycling of Dol-P derived from Man-P-Dol-mediated reactions in
      N-, O-, and C-mannosylation of proteins, GPI anchor assembly, and the three Glc-P
      Dol-mediated reactions in Glc(3)Man(9)GlcNAc(2)-P-P-Dol (DLO) biosynthesis.

PMID- 18077450
TI  - Nuclear respiratory factor 1 regulates all ten nuclear-encoded subunits of
      cytochrome c oxidase in neurons.
AB  - Cytochrome c oxidase (COX) is one of only four bigenomic proteins in mammalian
      cells, having ten subunits encoded in the nuclear genome and three in the
      mitochondrial DNA. The mechanism of its bigenomic control is not well understood.
      The ten nuclear subunits are on different chromosomes, and the possibility of
      their coordinate regulation by the same transcription factor(s) deserves serious
      consideration. The present study tested our hypothesis that nuclear respiratory
      factor 1 (NRF-1) serves such a role in subunit coordination. Following in silico
      analysis of murine nuclear-encoded COX subunit promoters, electrophoretic
      mobility shift and supershift assays indicated NRF-1 binding to all ten
      promoters. In vivo chromatin immunoprecipitation assays also showed NRF-1 binding
      to all ten promoters in murine neuroblastoma cells. Site-directed mutagenesis of
      putative NRF-1 binding sites confirmed the functionality of NRF-1 binding on all
      ten COX promoters. These sites are highly conserved among mice, rats, and humans.
      Silencing of NRF-1 with RNA interference reduced all ten COX subunit mRNAs and
      mRNAs of other genes involved in mitochondrial biogenesis. We conclude that NRF-1
      plays a significant role in coordinating the transcriptional regulation of all
      ten nuclear-encoded COX subunits in neurons. Moreover, NRF-1 is known to activate
      mitochondrial transcription factors A and B, thereby indirectly regulating the
      expressions of the three mitochondrial-encoded COX subunits. Thus, NRF-1 and our
      previously described NRF-2 prove to be the two key bigenomic coordinators for
      transcriptional regulation of all cytochrome c oxidase subunits in neurons.
      Possible interactions between the NRFs will be investigated in the future.

PMID- 18077453
TI  - Identification of cyclin A2 as the downstream effector of the nuclear
      phosphatidylinositol 4,5-bisphosphate signaling network.
AB  - In addition to the well characterized phosphoinositide second messengers derived
      from the plasma membrane, increasing evidence supports the existence of a nuclear
      phosphoinositide signaling network. The aim of this investigation was to dissect
      the role played by nuclear phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)
      in cell cycle progression and to determine the cell cycle regulatory component(s)
      that are involved. A number of cytosolic/nuclear PtdIns(4,5)P2-deficient Swiss
      3T3 cell lines were established, and their G 0/G 1/S cell cycle phase transitions
      induced by defined mitogens were examined. Our results demonstrate that nuclear
      PtdIns(4,5)P2 down-regulation caused a delay in phorbol ester-induced S phase
      entry and that this was at least in part channeled through cyclin A2 at the
      transcriptional level. In summary, these data identify cyclin A2 as a downstream
      effector of the nuclear PtdIns(4,5)P2 signaling network and highlight the
      importance of nuclear PtdIns(4,5)P2 in the regulation of mammalian mitogenesis.

PMID- 18077452
TI  - Neuralized-like 1 (Neurl1) targeted to the plasma membrane by N-myristoylation
      regulates the Notch ligand Jagged1.
AB  - Notch signaling constitutes an evolutionarily conserved mechanism that mediates
      cell-cell interactions in various developmental processes. Numerous regulatory
      proteins interact with the Notch receptor and its ligands and control signaling
      at multiple levels. Ubiquitination and endocytosis followed by endosomal sorting
      of both the receptor and its ligands is essential for Notch-mediated signaling.
      The E3 ubiquitin ligases, Neuralized (Neur) and Mind Bomb (Mib1), are crucial for
      regulating the activity and stability of Notch ligands in Drosophila; however,
      biochemical evidence that the Notch ligands are directly targeted for
      ubiquitination by Neur and/or Mib1 has been lacking. In this report, we explore
      the function of Neurl1, a mouse ortholog of Drosophila Neur. We show that Neurl1
      can function as an E3 ubiquitin ligase to activate monoubiquitination in vitro of
      Jagged1, but not other mammalian Notch ligands. Neurl1 expression decreases
      Jagged1 levels in cells and blocks signaling from Jagged1-expressing cells to
      neighboring Notch-expressing cells. We demonstrate that Neurl1 is myristoylated
      at its N terminus, and that myristoylation of Neurl1 targets it to the plasma
      membrane. Point mutations abolishing either Neurl1 myristoylation and plasma
      membrane localization or Neurl1 ubiquitin ligase activity impair its ability to
      down-regulate Jagged1 expression and to block signaling. Taken together, our
      results argue that Neurl1 at the plasma membrane can affect the signaling
      activity of Jagged1 by directly enhancing its ubiquitination and subsequent
      turnover.

PMID- 18077454
TI  - Dimeric structure of human Na+/H+ exchanger isoform 1 overproduced in
      Saccharomyces cerevisiae.
AB  - The Na(+)/H(+) exchanger isoform 1 (NHE1) is an integral membrane protein that
      regulates intracellular pH by extruding an intracellular H(+) in exchange for one
      extracellular Na(+). The human NHE1 isoform is involved in heart disease and cell
      growth and proliferation. Although details of NHE1 regulation and transport are
      being revealed, there is little information available on the structure of the
      intact protein. In this report, we demonstrate overexpression, purification, and
      characterization of the human NHE1 (hNHE1) protein in Saccharomyces cerevisiae.
      Overproduction of the His-tagged protein followed by purification via nickel
      nitrilotriacetic acid-agarose chromatography yielded 0.2 mg of pure protein/liter
      of cell culture. Reconstitution of hNHE1 in proteoliposomes demonstrated that the
      protein was active and responsive to an NHE1-specific inhibitor. Circular
      dichroism spectroscopy of purified hNHE1 revealed that the protein contains 41%
      alpha-helix, 23% beta-sheet, and 36% random coil. Size exclusion chromatography
      indicated that the protein-detergent micelle was in excess of 200 kDa, consistent
      with an hNHE1 dimer. Electron microscopy and single particle reconstruction of
      negatively stained hNHE1 confirmed that the protein was a dimer, with a compact
      globular domain assigned to the transmembrane region and an apical ridge assigned
      to the cytoplasmic domain. The transmembrane domain of the hNHE1 reconstruction
      was clearly dimeric, where each monomer had a size and shape consistent with the
      predicted 12 membrane-spanning segments for hNHE1.

PMID- 18077455
TI  - Clostridium botulinum C2 toxin. Identification of the binding site for
      chloroquine and related compounds and influence of the binding site on properties
      of the C2II channel.
AB  - Clostridium botulinum C2 toxin belongs to the family of binary AB type toxins
      that are structurally organized into distinct enzyme (A, C2I) and binding (B,
      C2II) components. The proteolytically activated 60-kDa C2II binding component is
      essential for C2I transport into target cells. It oligomerizes into heptamers and
      forms channels in lipid bilayer membranes. The C2II channel is cation-selective
      and can be blocked by chloroquine and related compounds. Residues 303-330 of C2II
      contain a conserved pattern of alternating hydrophobic and hydrophilic residues,
      which has been implicated in the formation of two amphipathic beta-strands
      involved in membrane insertion and channel formation. In the present study, C2II
      mutants created by substitution of different negatively charged amino acids by
      alanine-scanning mutagenesis were analyzed in artificial lipid bilayer membranes.
      The results suggested that most of the C2II mutants formed SDS-resistant
      oligomers (heptamers) similar to wild type. The mutated negatively charged amino
      acids did not influence channel properties with the exception of Glu(399) and
      Asp(426), which are probably localized in the vestibule near the channel
      entrance. These mutants show a dramatic decrease in their affinity for binding of
      chloroquine and its analogues. Similarly, F428A, which represents the Phi-clamp
      in anthrax protective antigen, was mutated in C2II in several other amino acids.
      The C2II mutants F428A, F428D, F428Y, and F428W not only showed altered
      chloroquine binding but also had drastically changed single channel properties.
      The results suggest that amino acids Glu(399), Asp(426), and Phe(428) have a
      major impact on the function of C2II as a binding protein for C2I delivery into
      target cells.

PMID- 18077456
TI  - SpoIIQ anchors membrane proteins on both sides of the sporulation septum in
      Bacillus subtilis.
AB  - During the process of spore formation in Bacillus subtilis, many membrane
      proteins localize to the polar septum where they participate in morphogenesis and
      signal transduction. The forespore membrane protein SpoIIQ plays a central role
      in anchoring several mother-cell membrane proteins in the septal membrane. Here,
      we report that SpoIIQ is also responsible for anchoring a membrane protein on the
      forespore side of the sporulation septum. Co-immunoprecipitation experiments
      reveal that SpoIIQ resides in a complex with the polytopic membrane protein
      SpoIIE. During the early stages of sporulation, SpoIIE participates in the switch
      from medial to polar division and co-localizes with FtsZ at the polar septum. We
      show that after cytokinesis, SpoIIE is released from the septum and transiently
      localizes to all membranes in the forespore compartment. Upon the initiation of
      engulfment, it specifically re-localizes to the septal membrane on the forespore
      side. Importantly, the re-localization of SpoIIE to the engulfing septum requires
      SpoIIQ. These results indicate that SpoIIQ is required to anchor membrane
      proteins on both sides of the division septum. Moreover, our data suggest that
      forespore membrane proteins can localize to the septal membrane by diffusion-and
      capture as has been described for membrane proteins in the mother cell. Finally,
      our results raise the intriguing possibility that SpoIIE has an uncharacterized
      function at a late stage of sporulation.

PMID- 18077457
TI  - Analysis and molecular modeling of the formation, structure, and activity of the
      phosphatidylserine-calcium-phosphate complex associated with biomineralization.
AB  - The nucleational core of matrix vesicles contains a complex (CPLX) of
      phosphatidylserine (PS), Ca(2+), and inorganic phosphate (P(i)) that is important
      to both normal and pathological calcification. Factors required for PS-CPLX
      formation and nucleational activity were studied using in vitro model systems and
      molecular dynamic simulations. Ca(2+) levels required for and rates of PS-CPLX
      formation were monitored by light scattering at 340 nm, assessing changes in
      amount and particle size. Fourier transform infrared spectroscopy was used to
      explore changes in chemical structure and composition. Washing with pH 5 buffer
      was used to examine the role of amorphous calcium phosphate in CPLX nucleational
      activity, which was assessed by incubation in synthetic cartilage lymph with
      varied pH values. Addition of 4 Ca(2+)/PS was minimally required to form viable
      complexes. During the critical first 10-min reaction period, rapid reduction in
      particle size signaled changes in PS-CPLX structure. Fourier transform infrared
      spectroscopy revealed increasing mineral phosphate that became progressively
      deprotonated to PO(4)(3-). This Ca(2+)-mediated effect was mimicked in part by
      increasing the Ca(2+)/PS reaction ratio. Molecular dynamic simulations provided
      key insight into initial interactions between Ca(2+) and P(i) and the carboxyl,
      amino, and phosphodiester groups of PS. Deduced interatomic distances agreed
      closely with previous radial distribution function x-ray-absorption fine
      structure measurements, except for an elongated Ca(2+)-N distance, suggesting
      additional changes in atomic structure during the critical 10-min ripening
      period. These findings clarify the process of PS-CPLX formation, reveal details
      of its structure, and provide insight into its role as a nucleator of crystalline
      calcium phosphate mineral formation.

PMID- 18077458
TI  - The RHOX5 homeodomain protein mediates transcriptional repression of the netrin-1
      receptor gene Unc5c.
AB  - The X-linked mouse Rhox gene cluster contains more than 30 homeobox genes that
      are candidates to regulate multiple steps in male and female gametogenesis. The
      founding member of the Rhox gene cluster, Rhox5, is an androgen-dependent gene
      expressed in Sertoli cells that promotes the survival and differentiation of the
      adjacent male germ cells. Here, we report the first identification and
      characterization of a Rhox5-regulated gene. This gene, Unc5c, encodes a pro
      apoptotic receptor with tumor suppressor activity that we found is negatively
      regulated by Rhox5 in the testis in vivo. Transfection analyses in cell lines of
      different origin indicated that Rhox5-dependent down-regulation of Unc5c requires
      another Sertoli cell-specific cofactor. Examination of other mouse Rhox family
      members revealed that mouse RHOX2 and RHOX3 also have the ability to down
      regulate Unc5c expression. The human RHOX protein PEPP2 (RHOXF2) also had this
      ability, indicating that Unc5c repression is a conserved RHOX-dependent response.
      Deletion analysis identified a Rhox5-responsive element in the Unc5c 5'
      untranslated region. Although 5'-untranslated regions typically house post
      transcriptional elements, several lines of evidence indicated that Rhox5 down
      regulates Unc5c at the transcriptional level. The repression of Unc5c expression
      by Rhox5 may, in part, mediate the pro-survival function of Rhox5 in the testis,
      as we found that Unc5c mutant mice have decreased germ cell apoptosis in the
      testis. Along with our other data, these findings led us to propose a model in
      which Rhox5 is a negative regulator upstream of Unc5c in a Sertoli-cell pathway
      that promotes germ-cell survival.

PMID- 18077460
TI  - Arginine methylation of the histone H3 tail impedes effector binding.
AB  - Histone tail post-translational modification results in changes in cellular
      processes, either by generating or blocking docking sites for histone code
      readers or by altering the higher order chromatin structure. H3K4me3 is known to
      mark the promoter regions of active transcription. Proteins bind H3K4 in a methyl
      dependent manner and aid in the recruitment of histone-remodeling enzymes and
      transcriptional cofactors. The H3K4me3 binders harbor methyl-specific chromatin
      binding domains, including plant homeodomain, Chromo, and tudor domains.
      Structural analysis of the plant homeodomains present in effector proteins, as
      well as the WD40 repeats of WDR5, reveals critical contacts between residues in
      these domains and H3R2. The intimate contact between H3R2 and these domain types
      leads to the hypothesis that methylation of this arginine residue antagonizes the
      binding of effector proteins to the N-terminal tail of H3. Here we show that H3
      tail binding effector proteins are indeed sensitive to H3R2 methylation and that
      PRMT6, not CARM1/PRMT4, is the primary methyltransferase acting on this site. We
      have tested the expression of a select group of H3K4 effector-regulated genes in
      PRMT6 knockdown cells and found that their levels are altered. Thus, PRMT6
      methylates H3R2 and is a negative regulator of N-terminal H3 tail binding.

PMID- 18077459
TI  - Role of NF-kappaB-dependent caveolin-1 expression in the mechanism of increased
      endothelial permeability induced by lipopolysaccharide.
AB  - We investigated the role of NF-kappaB activation by the bacterial product
      lipopolysaccharide (LPS) in inducing caveolin-1 (Cav-1) expression and its
      consequence in contributing to the leakiness of the endothelial barrier. We
      observed that LPS challenge of human lung microvascular endothelial cells induced
      concentration- and time-dependent increases in expression of Cav-1 mRNA and
      protein. The NEMO (NF-kappaB essential modifier binding domain)-binding domain
      peptide (IkB kinase (IKK)-NEMO-binding domain (NBD) peptide), which prevents NF
      kappaB activation by inhibiting the interaction of IKKgamma with the IKK complex,
      blocked LPS-induced Cav-1 mRNA and protein expression. Knockdown of NF-kappaB
      subunit p65/RelA expression with small interfering RNA also prevented LPS-induced
      Cav-1 expression. Caveolae open to the apical and basal plasmalemma of
      endothelial cells increased 2-4-fold within 4 h of LPS exposure. IKK-NBD peptide
      markedly reduced the LPS-induced increase in the number of caveolae as well as
      transendothelial albumin permeability. These observations were recapitulated in
      mouse studies in which IKK-NBD peptide prevented Cav-1 expression and interfered
      with the increase in lung microvessel permeability induced by LPS. Thus, LPS
      mediates NF-kappaB-dependent Cav-1 expression that results in increased caveolae
      number and thereby contributes to the mechanism of increased transendothelial
      albumin permeability.

PMID- 18077461
TI  - TRPV5 is internalized via clathrin-dependent endocytosis to enter a Ca2+
      controlled recycling pathway.
AB  - The epithelial Ca(2+) channel TRPV5 plays an essential role in transcellular
      Ca(2+) transport and is one of the most Ca(2+)-selective members of the transient
      receptor potential superfamily. Regulation of the abundance of TRPV5 at the cell
      surface is critical in body Ca(2+) homeostasis. However, little is known about
      the mechanisms underlying TRPV5 endo- and exocytosis. Here, we show that TRPV5 is
      constitutively internalized in a dynamin- and clathrin-dependent manner.
      Internalized TRPV5 first appears in small vesicular structures and then localizes
      to perinuclear structures positive for Rab11a. TRPV5 has a half-life of more than
      8 h and is stable even after internalization from the cell surface for more than
      3 h. Disruption of cell surface delivery of newly synthesized TRPV5 by brefeldin
      A does not reduce TRPV5-mediated Ca(2+) influx in cells, suggesting the presence
      of a stable intracellular pool of the channel capable of recycling back to the
      surface. Furthermore, the endocytic recycling kinetics is decreased upon
      treatment with Ca(2+) chelator BAPTA-AM, indicating that the channel's
      trafficking pathways are dynamically controlled by Ca(2+).

PMID- 18077462
TI  - The O2-scavenging flavodiiron protein in the human parasite Giardia intestinalis.
AB  - The flavodiiron proteins (FDP) are widespread among strict or facultative
      anaerobic prokaryotes, where they are involved in the response to nitrosative
      and/or oxidative stress. Unexpectedly, FDPs were fairly recently identified in a
      restricted group of microaerobic protozoa, including Giardia intestinalis, the
      causative agent of the human infectious disease giardiasis. The FDP from Giardia
      was expressed, purified, and extensively characterized by x-ray crystallography,
      stopped-flow spectroscopy, respirometry, and NO amperometry. Contrary to
      flavorubredoxin, the FDP from Escherichia coli, the enzyme from Giardia has high
      O(2)-reductase activity (>40 s(-1)), but very low NO-reductase activity
      (approximately 0.2 s(-1)); O(2) reacts with the reduced protein quite rapidly
      (milliseconds) and with high affinity (K(m) < or = 2 microM), producing H(2)O.
      The three-dimensional structure of the oxidized protein determined at 1.9A
      resolution shows remarkable similarities with prokaryotic FDPs. Consistent with
      HPLC analysis, the enzyme is a dimer of dimers with FMN and the non-heme di-iron
      site topologically close at the monomer-monomer interface. Unlike the FDP from
      Desulfovibrio gigas, the residue His-90 is a ligand of the di-iron site, in
      contrast with the proposal that ligation of this histidine is crucial for a
      preferential specificity for NO. We propose that in G. intestinalis the primary
      function of FDP is to efficiently scavenge O(2), allowing this microaerobic
      parasite to survive in the human small intestine, thus promoting its
      pathogenicity.

PMID- 18077463
TI  - Staphylococcus aureus DsbA does not have a destabilizing disulfide. A new
      paradigm for bacterial oxidative folding.
AB  - In Gram-negative bacteria, the introduction of disulfide bonds into folding
      proteins occurs in the periplasm and is catalyzed by donation of an energetically
      unstable disulfide from DsbA, which is subsequently re-oxidized through
      interaction with DsbB. Gram-positive bacteria lack a classic periplasm but
      nonetheless encode Dsb-like proteins. Staphylococcus aureus encodes just one Dsb
      protein, a DsbA, and no DsbB. Here we report the crystal structure of S. aureus
      DsbA (SaDsbA), which incorporates a thioredoxin fold with an inserted helical
      domain, like its Escherichia coli counterpart EcDsbA, but it lacks the
      characteristic hydrophobic patch and has a truncated binding groove near the
      active site. These findings suggest that SaDsbA has a different substrate
      specificity than EcDsbA. Thermodynamic studies indicate that the oxidized and
      reduced forms of SaDsbA are energetically equivalent, in contrast to the
      energetically unstable disulfide form of EcDsbA. Further, the partial
      complementation of EcDsbA by SaDsbA is independent of EcDsbB and biochemical
      assays show that SaDsbA does not interact with EcDsbB. The identical stabilities
      of oxidized and reduced SaDsbA may facilitate direct re-oxidation of the protein
      by extracellular oxidants, without the need for DsbB.

PMID- 18077464
TI  - Contribution of the GABA shunt to hypoxia-induced alanine accumulation in roots
      of Arabidopsis thaliana.
AB  - When subjected to low oxygen stress, plants accumulate alanine and gamma
      aminobutyric acid (GABA). To investigate the function of GABA metabolism under
      hypoxia and its contribution to alanine accumulation, we studied the genes that
      encode the two key enzymes of the GABA shunt, glutamate decarboxylase (GAD) and
      GABA transaminase (GABA-T). Among the five homologous GAD genes found in
      Arabidopsis thaliana, GAD1 expression was predominantly found in roots, while
      GAD2 expression was evident in all organs. Expression of the other three GAD
      genes was generally weak. In response to hypoxia, transcriptional induction was
      observed for GAD4 only. For GABA-T1, its expression was detected in all organs,
      but there was no significant transcriptional change under hypoxic conditions.
      Moreover, we have isolated and characterized Arabidopsis mutants defective in
      GAD1 and GABA-T1. In gad1 mutants, GAD activity was significantly reduced in
      roots but was not affected in shoots. In the gaba-t1 mutant, GABA-T activity was
      decreased to negligible levels in both shoots and roots. These mutants were
      phenotypically normal under normal growth conditions except for the reduced seed
      production of the pop2 mutants as described previously. However, metabolite
      analysis revealed significant changes in GABA content in gad1 and gaba-t1
      mutants. The levels of alanine under hypoxic conditions were also affected in the
      roots of gad1 and gaba-t1 mutants. The partial inhibition of the hypoxia-induced
      alanine accumulation in roots of these mutants suggests that the GABA shunt is,
      in part, responsible for the alanine accumulation under hypoxia.

PMID- 18077466
TI  - In vivo visualization of the water-refilling process in xylem vessels using X-ray
      micro-imaging.
AB  - BACKGROUND AND AIMS: Xylem vessels containing gases (embolized) must be refilled
      with water if they are to resume transport of water through the plant, so
      refilling is of great importance for the maintenance of water balance in plants.
      However, the refilling process is poorly understood because of inadequate
      examination methods. Simultaneous measurements of plant anatomy and vessel
      refilling are essential to elucidate the mechanisms involved. In the present
      work, a new technique based on phase-contrast X-ray imaging is presented that
      visualizes, in vivo and in real time, both xylem anatomy and refilling of
      embolized vessels. METHODS: With the synchrotron X-ray micro-imaging technique,
      the refilling of xylem vessels of leaves and a stem of Phyllostachys bambusoides
      with water is demonstrated under different conditions. The technique employs
      phase contrast imaging of X-ray beams, which are transformed into visible light
      and are photographed by a charge coupled device camera. X-ray images were
      captured consecutively at every 0.5 s with an exposure time of 10 ms. KEY
      RESULTS: The interface (meniscus) between the water and gas phases in refilling
      the xylem vessels is displayed. During refilling, the rising menisci in embolized
      vessels showed repetitive flow, i.e. they temporarily stopped at the end walls of
      the vessel elements while gas bubbles were removed. The meniscus then passed
      through the end wall at a faster rate than the speed of flow in the main vessels.
      In the light, the speed of refilling in a specific vessel was slower than that in
      the dark, but this rate increased again after repeated periods in darkness.
      CONCLUSIONS: Real-time, non-destructive X-ray micro-imaging is an important,
      useful and novel technique to study the relationship between xylem structure and
      the refilling of embolized vessels in intact plants. It provides new insight into
      understanding the mechanisms of water transport and the refilling of embolized
      vessels, which are not understood well.

PMID- 18077465
TI  - Cholinesterase inhibition modulates visual and attentional brain responses in
      Alzheimer's disease and health.
AB  - Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are
      considered more responsive to pro-cholinergic therapy than characteristic memory
      disturbances. We hypothesised that neural responses in AD during visuo
      attentional processing would be impaired relative to controls, yet partially
      susceptible to improvement with the cholinesterase inhibitor physostigmine. We
      studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI
      scanning to enable within-subject placebo-controlled comparisons of effects of
      physostigmine on stimulus- and attention- related brain activations, plus between
      group comparisons for these. Subjects viewed face or building stimuli while
      performing a shallow judgement (colour of image) or a deep judgement (young/old
      age of depicted face or building). Behaviourally, AD subjects performed slower
      than controls in both tasks, while physostigmine benefited the patients for the
      more demanding age-judgement task. Stimulus-selective (face minus building, and
      vice versa) BOLD signals in precuneus and posterior parahippocampal cortex were
      attenuated in patients relative to controls, but increased following
      physostigmine. By contrast, face-selective responses in fusiform cortex were not
      impaired in AD and showed decreases following physostigmine for both groups. Task
      dependent responses in right parietal and prefrontal cortices were diminished in
      AD but improved following physostigmine. A similar pattern of group and treatment
      effects was observed in two extrastriate cortical regions that showed
      physostigmine-induced enhancement of stimulus-selectivity for the deep versus
      shallow task. Finally, for the healthy group, physostigmine decreased stimulus
      and task-dependent effects, partly due to an exaggeration of selectivity during
      the shallow relative to deep task. The differences in brain activations between
      groups and treatments were not attributable merely to performance (reaction time)
      differences. Our results demonstrate that physostigmine can improve both stimulus
      and attention-dependent responses in functionally affected extrastriate and
      frontoparietal regions in AD, while perturbing the normal pattern of responses in
      many of the same regions in healthy controls.

PMID- 18077467
TI  - Surface hydrophobicity causes SO2 tolerance in lichens.
AB  - BACKGROUND AND AIMS: The superhydrophobicity of the thallus surface in one of the
      most SO(2)-tolerant lichen species, Lecanora conizaeoides, suggests that surface
      hydrophobicity could be a general feature of lichen symbioses controlling their
      tolerance to SO(2). The study described here tests this hypothesis. METHODS:
      Water droplets of the size of a raindrop were placed on the surface of air-dry
      thalli in 50 lichen species of known SO(2) tolerance and contact angles were
      measured to quantify hydrophobicity. KEY RESULTS: The wettability of lichen
      thalli ranges from strongly hydrophobic to strongly hydrophilic. SO(2) tolerance
      of the studied lichen species increased with increasing hydrophobicity of the
      thallus surface. Extraction of extracellular lichen secondary metabolites with
      acetone reduced, but did not abolish the hydrophobicity of lichen thalli.
      CONCLUSIONS: Surface hydrophobicity is the main factor controlling SO(2)
      tolerance in lichens. It presumably originally evolved as an adaptation to wet
      habitats preventing the depression of net photosynthesis due to supersaturation
      of the thallus with water. Hydrophilicity of lichen thalli is an adaptation to
      dry or humid, but not directly rain-exposed habitats. The crucial role of surface
      hydrophobicity in SO(2) also explains why many markedly SO(2)-tolerant species
      are additionally tolerant to other (chemically unrelated) toxic substances
      including heavy metals.

PMID- 18077470
TI  - EMAGE--Edinburgh Mouse Atlas of Gene Expression: 2008 update.
AB  - EMAGE (http://genex.hgu.mrc.ac.uk/Emage/database) is a database of in situ gene
      expression patterns in the developing mouse embryo. Domains of expression from
      raw data images are spatially integrated into a set of standard 3D virtual mouse
      embryos at different stages of development, allowing data interrogation by
      spatial methods. Sites of expression are also described using an anatomy ontology
      and data can be queried using text-based methods. Here we describe recent
      enhancements to EMAGE which include advances in spatial search methods including:
      a refined local spatial similarity search algorithm, a method to allow global
      spatial comparison of patterns in EMAGE and subsequent hierarchical-clustering,
      and spatial searches across multiple stages of development. In addition, we have
      extended data access by the introduction of web services and new HTML-based
      search interfaces, which allow access to data that has not yet been spatially
      annotated. We have also started incorporating full 3D images of gene expression
      that have been generated using optical projection tomography (OPT).

PMID- 18077471
TI  - KEGG for linking genomes to life and the environment.
AB  - KEGG (http://www.genome.jp/kegg/) is a database of biological systems that
      integrates genomic, chemical and systemic functional information. KEGG provides a
      reference knowledge base for linking genomes to life through the process of
      PATHWAY mapping, which is to map, for example, a genomic or transcriptomic
      content of genes to KEGG reference pathways to infer systemic behaviors of the
      cell or the organism. In addition, KEGG provides a reference knowledge base for
      linking genomes to the environment, such as for the analysis of drug-target
      relationships, through the process of BRITE mapping. KEGG BRITE is an ontology
      database representing functional hierarchies of various biological objects,
      including molecules, cells, organisms, diseases and drugs, as well as
      relationships among them. KEGG PATHWAY is now supplemented with a new global map
      of metabolic pathways, which is essentially a combined map of about 120 existing
      pathway maps. In addition, smaller pathway modules are defined and stored in KEGG
      MODULE that also contains other functional units and complexes. The KEGG resource
      is being expanded to suit the needs for practical applications. KEGG DRUG
      contains all approved drugs in the US and Japan, and KEGG DISEASE is a new
      database linking disease genes, pathways, drugs and diagnostic markers.

PMID- 18077472
TI  - Biomedical ontologies: a functional perspective.
AB  - The information explosion in biology makes it difficult for researchers to stay
      abreast of current biomedical knowledge and to make sense of the massive amounts
      of online information. Ontologies--specifications of the entities, their
      attributes and relationships among the entities in a domain of discourse--are
      increasingly enabling biomedical researchers to accomplish these tasks. In fact,
      bio-ontologies are beginning to proliferate in step with accruing biological
      data. The myriad of ontologies being created enables researchers not only to
      solve some of the problems in handling the data explosion but also introduces new
      challenges. One of the key difficulties in realizing the full potential of
      ontologies in biomedical research is the isolation of various communities
      involved: some workers spend their career developing ontologies and ontology
      related tools, while few researchers (biologists and physicians) know how
      ontologies can accelerate their research. The objective of this review is to give
      an overview of biomedical ontology in practical terms by providing a functional
      perspective--describing how bio-ontologies can and are being used. As biomedical
      scientists begin to recognize the many different ways ontologies enable
      biomedical research, they will drive the emergence of new computer applications
      that will help them exploit the wealth of research data now at their fingertips.

PMID- 18077473
TI  - Application of Monte Carlo calculation and OEDIPE software for virtual
      calibration of an in vivo counting system.
AB  - OEDIPE (a French acronym standing for 'Tool for Personalized Internal Dose
      Assessment'), developed by IRSN, is used to perform virtual calibration of a real
      in vivo counting system. The system, installed recently at Le Vesinet, consists
      of four Broad Energy germanium detectors. CT images of Livermore torso phantom
      are used to create a voxel phantom after segmentation using Dosigray software.
      Virtual calibration using the voxel phantom was validated by the comparison of
      peak efficiencies between Monte Carlo calculation and phantom experiments using
      lung sources 152Eu and 241Am at different chest wall thickness (CWT = 19, 25, 30,
      43 mm). The comparison between virtual calibration and physical phantom
      experiments shows that the relative deviations are within +/- 10% in the energy
      range of 59.5-1408 keV, and within +/- 30% for 17.5 keV photons.

PMID- 18077474
TI  - Sleep quality in young adults with very low birth weight--the Helsinki study of
      very low birth weight adults.
AB  - OBJECTIVE: To assess the relationship between very low birth weight (VLBW; <1,500
      g) and quality and amount of sleep in young adults. METHODS: We compared 89 VLBW
      and 78 term-born 19- to 26-year-old adults, by actigraphy and the Basic Nordic
      Sleep Questionnaire. RESULTS: There were no group differences in sleep quality or
      amount (p's >.15), although VLBW adults went to bed on average 36 min earlier
      (95% confidence interval 6-66 min). Shorter gestational age was related to longer
      sleep latency both within VLBW (standardized regression coefficient beta = -.36,
      p =.040) and term-born adults (beta = -.25, p =.029). CONCLUSION: Adults with
      VLBW had similar quality and amount of sleep as those born at term, although VLBW
      adults went to bed earlier, suggesting an advanced sleep phase. Within each
      group, a lower gestational age was related to a longer sleep onset.

PMID- 18077475
TI  - Intake of ruminant trans fatty acids and risk of coronary heart disease.
AB  - BACKGROUND: Studies have shown a positive association between trans fatty acids
      (TFA) intake and risk of coronary heart disease (CHD), primarily accounted for by
      industrially produced TFA. Some of these studies indicate an inverse association
      between ruminant TFA (R-TFA) intake and CHD implying that R-TFA intake is
      innocuous or even protective against CHD. The aim of this study was to describe
      the association between R-TFA intake and risk of CHD evaluating both the absolute
      and the energy-adjusted intake. METHODS: The study was an 18-year follow-up study
      of 3686 Danes, aged 30-71 years, at baseline without previous CHD. RESULTS: There
      were no overall associations between absolute or energy-adjusted R-TFA intakes
      and risk of CHD. However, among women, indications of inverse associations
      between R-TFA intake and risk of CHD were found: hazard ratio (HR) per 0.5 g
      increase in absolute R-TFA intake = 0.84 [95% confidence interval (CI): 0.70,
      1.01] and HR per 0.5 g increase in energy-adjusted R-TFA intake = 0.77 (95% CI:
      0.55, 1.09). No associations between absolute or energy-adjusted R-TFA intakes
      and CHD were found among men. CONCLUSIONS: This study suggests that R-TFA intake
      is not associated with a higher risk of CHD. Whether R-TFA intake is even
      protective against CHD among women cannot be concluded from this study.

PMID- 18077476
TI  - Topiramate, nutrition and weight change: a prospective study.
AB  - PURPOSE: To evaluate prospectively the relationship between appetite, food
      composition, nutritional habits and weight loss following administration of
      topiramate (TPM) and to identify predictors for TPM induced weight loss. METHODS:
      22 patients with epilepsy who were started on TPM were prospectively followed for
      6 months and contacted again after a mean follow-up time of 37.1 months. RESULTS:
      Body mass index (BMI) loss occurred in 59% of patients, with a mean weight loss
      of 9.5 kg after 6 months while receiving TPM without further weight loss at the
      long term follow-up. Weight loss was associated with reduction in appetite
      without affecting food composition. Predictors for BMI loss after 6 months were
      high initial BMI and body fat. After 3 weeks of treatment with TPM, the recorded
      parameters did not predict BMI loss but at 3 months, weight loss, reduction of
      appetite and amount of food intake were predictive for the amount of BMI loss
      after 6 months.

PMID- 18077477
TI  - Self-perceived memory impairment and cognitive performance in an elderly
      independent population with age-related white matter changes.
AB  - OBJECTIVES: To determine whether self-perceived memory impairment is associated
      with the severity of white matter changes (WMC) and is related to cognitive
      impairment. METHODS: Data were drawn from the multinational Leukoaraiosis and
      Disability Study (LADIS), which investigates the impact of WMC on global
      functioning. WMC severity was rated using the Fazekas scale. Medial temporal lobe
      atrophy (MTA) was scored visually and mean values were calculated. The
      neuropsychological battery consisted of the Mini-Mental State Examination, a
      modified version of the VADAS-Cog, Trail making and Stroop tests. A question
      about self-perceived memory impairment was used as a measure for presence of
      memory complaints. Cognitive performance was analysed test-by-test and in three
      main domains: memory, executive functions and speed/motor control. The Geriatric
      Depression Scale (GDS) was used as a measure of depressive symptoms. RESULTS: Six
      hundred and thirty-eight subjects were included in this study. No association was
      found between memory complaints and the severity of WMC. Subjects with memory
      complaints (n = 399) had a higher GDS score [t((637)) = -7.15; p<0.02] and
      performed worse on almost all cognitive tests and on the three cognitive domains.
      Multiple linear regression showed that the worse performance on the memory domain
      was associated with memory complaints independently of depressive symptoms, WMC
      severity and MTA (R(2) = 0.183; F = 17.09, beta = -0.126; p<0.05). CONCLUSION: In
      a sample of non-disabled elderly subjects with WMC, self-perceived memory
      impairment is significantly associated with objective memory impairment
      independently of the WMC severity, depressive symptoms and MTA.

PMID- 18077478
TI  - Call-Fleming syndrome associated with subarachnoid haemorrhage: three new cases.
AB  - BACKGROUND: The Call-Fleming syndrome (CFS) comprises acute severe recurrent
      (thunderclap) headaches, occasional transient or fluctuating neurological
      abnormalities and reversible segmental cerebral vasoconstriction. It is a benign
      condition with an excellent prognosis, yet because it is often clinically and
      radiologically similar to a number of commonly encountered conditions, diagnostic
      difficulties may arise, leading to inappropriate, and even potentially harmful,
      investigative and therapeutic approaches. CASES: Three personal cases are
      presented to highlight the occurrence of subarachnoid haemorrhage (SAH) as part
      of CFS. In two patients with a positive CT head, SAH involved the sulci in the
      upper cerebral convexity, an unusual location in aneurysmal SAH. RESULTS: SAH is
      not an uncommon feature of CFS, occurring in approximately 25% of reported cases,
      and may pose a diagnostic challenge. CFS has a relatively characteristic spectrum
      of features, allowing a confident diagnosis in most cases, even when atypical
      features such as SAH are present. CONCLUSIONS: Recognising the spectrum of
      abnormalities seen in CFS, including particularly SAH, allows a sound approach to
      a safe diagnosis.

PMID- 18077479
TI  - Novel epidemiological features of moyamoya disease.
AB  - BACKGROUND: Many clinical features that are specific to moyamoya disease have
      been reported and cited in textbooks based on previous data. The purpose of this
      study is to investigate the present epidemiological features of moyamoya disease
      based on recently obtained regional all-inclusive data. METHODS: The authors
      performed an all-inclusive survey of moyamoya disease in Hokkaido, one of the
      major islands in Japan that has a population of 5.63 million. The epidemiological
      features were analysed based on the data from 267 newly registered patients with
      moyamoya disease in Hokkaido from 2002 to 2006. These analysed data were adjusted
      to the whole Japanese population at 2005. RESULTS: The detection rate of the
      disease per year was 0.94 patients per 100,000 people, and prevalence was 10.5
      patients per 100,000 people. The incidence of ischaemia concerned with the
      disease was 0.53 patients per 100,000 people-years and haemorrhage was 0.2
      patients per 100,000 people-years. The ratio of female to male patients was 2.18.
      The ratio of patients aged 10 years and above to under 10 years of age at onset
      was 6.18. Two peaks for age of onset were seen: the highest was observed between
      45 and 49 years, and the second between 5 and 9 years. Asymptomatic patients
      comprised 17.8% of the total number of patients. CONCLUSION: The epidemiological
      features of moyamoya disease determined by this survey varied considerably from
      previous data. The detection rate and prevalence of the disease were higher than
      those reported previously. The highest peak of onset age was older than those
      reported previously. In addition, it was revealed that asymptomatic moyamoya
      patients are not always rare in Japan.

PMID- 18077480
TI  - Predicting short-term disability progression in early multiple sclerosis: added
      value of MRI parameters.
AB  - OBJECTIVE: Magnetic resonance imaging (MRI) and clinical parameters are
      associated with disease progression in multiple sclerosis (MS). The aim of this
      study was to investigate whether adding MRI parameters to a model with only
      clinical parameters could improve these associations. METHODS: 89 patients (55
      women) with recently diagnosed MS had clinical and MRI evaluation at baseline
      (time of diagnosis) and at follow-up after 2.2 years. Detailed clinical data were
      available, including disease type (relapse-onset or progressive-onset) and
      disability, as measured by the Expanded Disability Status Scale (EDSS). MRI
      parameters included Normalised Brain Volume (NBV) at baseline, percentage brain
      volume change (PBVC/year), T2- and T1-lesion loads and spinal cord abnormalities.
      Progression of disability (increase in EDSS of at least 1 point at follow-up) was
      the main outcome measure. For a model containing only clinical parameters, the
      added value of MRI parameters was tested using logistic regression. RESULTS:
      PBVC/year and lesion loads at follow-up were significantly higher in the group
      with progression. Adding PBVC/year to a clinical model improved the model,
      indicating that MRI parameters added independent information (p<0.001).
      CONCLUSION: The rate of cerebral atrophy conveys added information for the
      progression of disability in patients with early MS, suggesting that clinical
      disability is determined by neurodegenerative changes as depicted by MRI.

PMID- 18077482
TI  - Impact of collateral flow on tissue fate in acute ischaemic stroke.
AB  - BACKGROUND: Collaterals may sustain penumbra prior to recanalisation yet the
      influence of baseline collateral flow on infarct growth following endovascular
      therapy remains unknown. METHODS: Consecutive patients underwent serial diffusion
      and perfusion MRI before and after endovascular therapy for acute cerebral
      ischaemia. We assessed the relationship between MRI diffusion and perfusion
      lesion indices, angiographic collateral grade and infarct growth. Tmax perfusion
      lesion maps were generated and diffusion-perfusion mismatch regions were divided
      into Tmax >or=4 s (severe delay) and Tmax >or=2 but <4 s (mild delay). RESULTS:
      Among 44 patients, collateral grade was poor in 7 (15.9%), intermediate in 20
      (45.5%) and good in 17 (38.6%) patients. Although diffusion-perfusion mismatch
      volume was not different depending on the collateral grade, patients with good
      collaterals had larger areas of milder perfusion delay than those with poor
      collaterals (p = 0.005). Among 32 patients who underwent day 3-5 post-treatment
      MRIs, the degree of pretreatment collateral circulation (r = -0.476, p = 0.006)
      and volume of diffusion-perfusion mismatch (r = 0.371, p = 0.037) were correlated
      with infarct growth. Greatest infarct growth occurred in patients with both non
      recanalisation and poor collaterals. Multiple regression analysis revealed that
      pretreatment collateral grade was independently associated with infarct growth.
      CONCLUSION: Our data suggest that angiographic collateral grade and penumbral
      volume interactively shape tissue fate in patients undergoing endovascular
      recanalisation therapy. These angiographic and MRI parameters provide
      complementary information about residual blood flow that may help guide treatment
      decision making in acute cerebral ischaemia.

PMID- 18077483
TI  - Upgrading to biventricular pacing/defibrillation systems in right ventricular
      paced congestive heart failure patients: prospective assessment of procedural
      parameters and response rate.
AB  - AIMS: Cardiac resynchronization therapy (CRT) is indicated in patients with heart
      failure and bundle branch block. It is less clear whether this includes patients
      with pre-existing right ventricular pacemaker/defibrillator systems, particularly
      with respect to implantation success and clinical benefit. METHODS AND RESULTS:
      In consecutive patients scheduled for CRT, we prospectively compared implantation
      success, procedural parameters, and clinical response in 'de novo' vs. upgrade
      procedures of previously implanted right ventricular systems. CRT implantation
      was attempted in 79 consecutive patients (64 +/- 11 years, 63 male, 38 ischaemic,
      41 non-ischaemic cardiomyopathy). De novo implantation was performed in 61
      patients, upgrade procedures in 18 patients. Implant success (92 vs. 94%, P =
      1.00), procedure duration (153 +/- 43 vs. 164 +/- 65 min, P = 0.51), fluoroscopy
      time (25 +/- 18 vs. 32 +/- 22 min, P = 0.18) or dose (40 +/- 31 vs. 52 +/- 49
      Gy/cm(2), P = 0.35), and response rate (66 vs. 59%, P = 0.5) were comparable for
      both groups. CONCLUSION: Procedural aspects, implantation success, and clinical
      response to CRT were comparable for patients undergoing de-novo vs. upgrade
      procedures. Accordingly, patient selection for upgrading should be the same as
      for new CRT implantation.

PMID- 18077484
TI  - Characterization of focal right atrial appendage tachycardia.
AB  - AIMS: Though right atrial appendage tachycardia (RAAT) has been described, no
      studies to date have focused on its clinical characterization. The aim of the
      present study was to analyze its clinical, electrocardiographic (ECG), and
      electrophysiologic (EP) characteristics and the results of radiofrequency
      ablation (RFA) in RAAT. METHODS AND RESULTS: Out of 186 consecutive patients
      undergoing RFA for AT, 15 (8%) had focal RAAT. Mapping was performed using
      conventional catheters or a 3D electroanatomic mapping system. Patients with RAAT
      were more likely to be male (66 vs. 38%; P= 0.013) and younger (32 +/- 12.6 vs.
      55 +/- 13.2 years; P < 0.001) than patients with AT originating elsewhere. They
      were also more likely to have dyspnea (27 vs. 7.6%; P = 0.03), incessant
      tachycardia (53 vs. 16%; P < 0.001), and left ventricular systolic dysfunction
      (27 vs. 5%; P = 0.018). RFA was effective in all patients (100 vs. 75%; P =
      0.022) and no recurrences (0 vs. 8%; P = 0.31) were observed during a mean follow
      up of 37 +/- 36 months. A specific ECG pattern was identified, consisting of
      negative P-waves in leads V1-V2 and a transition to positivity in the rest of the
      precordial leads. This ECG pattern correctly identified RAAT with a sensitivity
      of 100%, a specificity of 98%, a positive predictive value of 88%, and a negative
      predictive value of 100%. CONCLUSION: Right atrial appendage tachycardia is more
      prevalent in young male patients and is commonly associated with
      tachycardiomyopathy. RFA is effective over long-term follow-up. A characteristic
      ECG pattern identifies RAAT with a very high sensitivity and specificity.

PMID- 18077485
TI  - COBRA combination therapy in daily practice--getting back to the future.

PMID- 18077486
TI  - Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated
      chondrocyte suppress the responses of type II collagen-reactive T cells in
      rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a T-cell-mediated systematic disease and
      is usually accompanied by articular cartilage damage. In the present study, we
      explored the effects of bone marrow-derived mesenchymal stem cells (MSCs) and MSC
      differentiated chondrocytes (MSC-chondrocytes) on the responses of antigen
      specific T cells in RA to type II collagen (CII) to evaluate the potential
      therapeutic value of MSCs in RA treatment. METHODS: The effects of both MSCs and
      MSC-chondrocytes on the proliferation, activation-antigen expression (CD69 and
      CD25) and cytokine production [interferon-gamma (IFN-gamma), tumour necrosis
      factor-alpha (TNF-alpha), interleukin (IL)-10 and IL-4] of CII-reactive T cells
      in RA patients were investigated with the stimulation of CII or otherwise.
      CD3/annexin V staining was used to evaluate T-cell apoptosis in the inhibition.
      The role of transforming growth factor-beta1 (TGF-beta1) underlying the
      inhibition was also investigated. RESULTS: MSCs failed to elicit positive
      responses of CII-reactive T cells, whereas they significantly suppressed CII
      stimulated T-cell proliferation and activation-antigen expression in a dose
      dependent fashion without inducing T-cell apoptosis. The inhibition was observed
      even after MSCs were added as late as 3 days after the initiation of stimulation.
      Moreover, MSCs inhibited both CD4+ and CD8+ T cells from producing IFN-gamma and
      TNF-alpha, while they up-regulated the levels of IL-10 and restored the secretion
      of IL-4. TGF-beta1 was confirmed to play a critical role in the inhibition.
      Throughout our study, MSC-chondrocytes shared similar properties with MSCs.
      CONCLUSION: Both MSCs and MSC-chondrocytes suppressed CII-reactive T-cell
      responses to CII in RA, which suggested that MSCs could be a potential candidate
      for RA treatment in future if further confirmed in vivo.

PMID- 18077487
TI  - Influence of glucosamine sulphate on oxidative stress in human osteoarthritic
      chondrocytes: effects on HO-1, p22(Phox) and iNOS expression.
AB  - OBJECTIVE: Reactive oxygen species (ROS) are major determinants in the alteration
      of articular cartilage. Among protective cellular mechanisms, the inducible
      isoform of haem oxygenase (HO-1) plays a particularly relevant role. On the other
      hand, the enzymatic activity of the Nicotinamide adenine dinucleotide phosphate
      (NADPH) system could contribute to the generation of ROS. Glucosamine sulphate
      (GS) is one of the drugs used in the treatment of osteoarthritis; however, its
      mechanism of action is still largely unknown. The aim of the present study was to
      investigate the effects of GS on primary human chondrocytes in vitro, in
      particular with regard to HO-1, p22(Phox) (a subunit of NADPH complex) and
      inducible nitric oxide synthase (iNOS) expression. METHODS: Primary human
      chondrocytes were treated with different concentrations of GS; gene expression of
      HO-1, p22(Phox) and iNOS was assessed by the reverse transcriptase-polymerase
      chain reaction method. In a separate set of experiments, the cells were
      stimulated with human recombinant interleukin (IL)-1beta and simultaneously
      treated with GS. Moreover, HO-1 protein and total nitrite production were
      evaluated. RESULTS: HO-1 gene expression was up-regulated (+40% with respect to
      the controls, P < 0.001) by 10 mmol/l GS at 24 h, while p22(Phox) gene expression
      was down-regulated by 10 mmol/l GS with a maximum inhibitory effect observed
      after 48 h treatment. IL-1beta stimulation induced expression of iNOS reverted by
      1 and 10 mmol/l GS. Moreover, HO-1 gene expression was down-regulated by IL-1beta
      and 10 mmol/l GS restored baseline values. These data were confirmed by
      evaluating HO-1 protein level and nitrite production. CONCLUSIONS: The influence
      of GS on oxidative stress observed in this study discloses a possible new
      mechanism of action and seems to be in keeping with a potential protective effect
      on chondrocyte population.

PMID- 18077488
TI  - Lower density of synovial nerve fibres positive for calcitonin gene-related
      peptide relative to substance P in rheumatoid arthritis but not in
      osteoarthritis.
AB  - OBJECTIVES: Sensory nerve fibres (NFs) contain two major neuropeptides, substance
      P (SP) and calcitonin gene-related peptide (CGRP). The pro-inflammatory role of
      SP is known, while CGRP has anti-inflammatory activities by inhibiting T helper
      type 1 cytokines, TNF secretion and leucocyte proliferation. We demonstrated the
      increase of SP-positive NFs in RA as compared with OA. This study investigated
      the density of CGRP-positive NFs relative to SP-positive NFs or sympathetic NFs
      in synovial tissue of patients with RA and OA. METHODS: By immunofluorescent
      staining of synovial tissue of 25 patients with RA and 35 patients with OA, NFs
      positive for CGRP, SP and tyrosine hydroxylase (sympathetic NFs) were quantified.
      RESULTS: Density of CGRP-positive NFs was higher in OA than in RA, and density of
      SP-positive NFs tended to be higher in RA. In RA patients, comparison of CGRP
      positive and SP-positive NFs in the same synovial tissue demonstrated less CGRP
      positive than SP-positive NFs. The ratio of CGRP-positive NFs to SP-positive NFs
      was lower in RA as compared with OA. In OA, but not in RA, density of CGRP
      positive NFs positively correlated with density of sympathetic NFs, which is much
      lower in RA patients. CONCLUSION: The preponderance of SP-positive NFs over CGRP
      positive NFs or sympathetic NFs most probably supports the pro-inflammatory
      process in patients with RA. The reasons for the loss of CGRP in sensory NFs are
      not known.

PMID- 18077489
TI  - Effect of matrix metalloproteinase-3 functional SNP on serum matrix
      metalloproteinase-3 level and outcome measures in Japanese RA patients.
AB  - OBJECTIVE: A bi-allelic polymorphism on the promoter region, -1612 ins/del A, was
      found to influence the production of MMP-3. Since MMP-3 plays a particularly
      pivotal role in joint destruction, the MMP-3 gene is thought to be an interesting
      target gene of disease severity in RA. We attempt to determine whether the MMP-3
      promoter polymorphism is associated with serum titre of MMP-3, disease activity
      and severity in Japanese RA patients. METHODS: DNA samples were obtained from
      1504 RA patients as part of the Institute of Rheumatology Rheumatoid Arthritis
      observational cohort study. From the 2006 spring data, serum MMP-3 levels of 820
      patients were available by enzyme immunoassay. Joint damage score at 5-yr disease
      duration could be measured using the Sharp/van der Heijde method in 162 patients.
      Genotyping of -1612 ins/del A was performed using fluorescent-labelled fragment
      analysis. Differences in serum MMP-3 level and joint damage score among genotypes
      of -1612 ins/del A polymorphism were analysed by linear regression analysis.
      RESULTS: No significant differences were found among MMP-3 genotypes on patient
      characteristics including disease activity score (P = 0.51) or health assessment
      questionnaire (P = 0.99). A significant effect of risk allele on serum MMP-3
      level was observed (P = 0.038), while no significant effect was observed on
      radiographic joint damage (P = 0.47). CONCLUSION: We conclude that MMP-3
      functional polymorphism is associated with serum MMP-3 titre, but is not a direct
      predictor for outcome measures in Japanese RA patients.

PMID- 18077490
TI  - CXCL10 (alpha) and CCL2 (beta) chemokines in systemic sclerosis--a longitudinal
      study.
AB  - OBJECTIVES: To measure serum levels of CXCL10 and CCL2 chemokines in patients
      with SSc, and relate the findings to clinical phenotype and disease progression.
      METHODS: Serum CXCL10 and CCL2 were assayed in 72 consecutive newly diagnosed SSc
      patients and in 72 sex- and age-matched controls. In 37 SSc and 37 controls,
      serum CXCL10 and CCL2 were re-evaluated 5 yrs later. RESULTS: SSc at onset showed
      significantly higher CXCL10 serum levels than controls (216 +/- 126 vs 92 +/- 53
      pg/ml; P < 0.0001), as well as CCL2 (388 +/- 172 vs 318 +/- 120 pg/ml; P = 0.01).
      CXCL10 was significantly increased in SSc with interstitial lung involvement or
      with kidney involvement (P = 0.01 and P = 0.02, respectively). A significant
      decrease of CXCL10 was observed from the baseline after 5 yrs in SSc (137 +/- 112
      vs 270 +/- 122 pg/ml, respectively; P < 0.0001), while no significant change was
      observed for CCL2 (418 +/- 176 vs 405 +/- 164 pg/ml; P = NS); the CCL2/CXCL10
      ratio significantly increased at the fifth year (1.7 +/- 0.8 vs 3.5 +/- 2.5; P <
      0.0001). No significant variations were observed in controls from the basal to
      the 5-yr evaluation with regards to CXCL10, CCL2 or CCL2/CXCL10 ratio.
      CONCLUSIONS: Our study demonstrates high serum levels of CXCL10 (Th1) and CCL2
      (Th2) chemokines in newly diagnosed SSc. High values of CXCL10 are associated
      with a more severe clinical phenotype (lung and kidney involvement). CXCL10
      declined during the follow-up, while CCL2 remained unmodified, suggesting that
      the disease progresses from the early Th1 inflammatory condition to the advanced
      Th2-like stage.

PMID- 18077491
TI  - Mural inflammatory hyperenhancement in MRI of giant cell (temporal) arteritis
      resolves under corticosteroid treatment.
AB  - OBJECTIVE: To determine the effect of corticosteroid treatment on mural
      inflammatory hyperenhancement in MRI in GCA. METHODS: MRI of the superficial
      temporal artery with sub-millimetre in-plane spatial resolution (195 x 260
      microm) was performed in 17 patients with proven GCA at the initiation of
      corticosteroid treatment and after 16 months of therapy. Visual MRI scores for
      mural inflammation were correlated with clinical and laboratory findings.
      RESULTS: Intensity of inflammatory hyperenhancement decreased significantly under
      corticosteroid therapy (2.3 +/- 0.6 vs 0.5 +/- 0.6, P < 0.001, with MRI score >2
      indicating vasculitis). This finding correlated with the clinical and serological
      remission in 15/17 patients. Of the two patients with active disease, one had
      persisting mural inflammation in MRI indicative of relapsing disease. The other
      patient presenting with signs of polymyalgia rheumatica had no inflammatory
      changes of the superficial temporal arteries on MRI scan at follow-up.
      CONCLUSIONS: Mural contrast enhancement in high-resolution MRI is pronounced in
      active disease and decreases under corticosteroid treatment, correlating well
      with laboratory remission.

PMID- 18077492
TI  - The direct healthcare costs associated with ankylosing spondylitis patients
      attending a UK secondary care rheumatology unit.
AB  - OBJECTIVES: To explore the direct healthcare resources associated with ankylosing
      spondylitis (AS) in the UK. A secondary objective was to establish if resources,
      and thus healthcare costs, vary by disease severity. METHODS: Medical records of
      147 sequential AS patients attending a UK secondary care rheumatology unit were
      examined to assess the direct healthcare resources used over the previous 12
      months. Starting with a detailed inventory and measurement of resources consumed,
      unit cost multipliers were applied to the quantity of each type of resource
      consumed. The mean cost per patient was estimated using the total cost divided by
      the number of patients included. RESULTS: The mean (median) annual cost per
      patient was 1852 pounds sterling (892 pounds sterling). The distribution of cost
      data was skewed, with 11% of patients incurring 50% of the total costs. The three
      most relevant cost domains were physiotherapy, hospitalization and medication
      costs at 32, 21 and 20% of the total costs, respectively. Twenty percent of the
      patients received physiotherapy, 13% received inpatient care and almost all
      incurred medication costs. Thirty-four percent of patients were prescribed
      disease-modifying anti-rheumatic drugs and 85% non-steroidal anti-inflammatory
      drugs. Over 50% of patients had at least one comorbidity. CONCLUSION: Direct
      costs accelerate steeply with disease activity (Bath Ankylosing Spondylitis
      Disease Activity Index >6.0) and increasing loss of function (Bath Ankylosing
      Spondylitis Functional Index >6.0) in patients with AS. The most severely
      affected patients incur 50% of the total costs, and physiotherapy accounts for
      32% of the total healthcare costs in the UK.

PMID- 18077493
TI  - Long-term exposure to medium-dose glucocorticoid therapy associates with
      hypertension in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) associates with increased cardiovascular
      morbidity and mortality that is due to both traditional and novel cardiovascular
      risk factors. Hypertension (HT), one of the most common risk factors for
      cardiovascular disease, is highly prevalent in RA. The effects of long-term
      glucocorticoid (GC) therapy on blood pressure have not been established yet. This
      study examined whether GC exposure associates with HT in patients with RA.
      METHODS: Four hundred consecutive RA patients with detailed clinical and
      laboratory assessments were categorized into three groups according to GC
      exposure: no or limited exposure (N/L-E); a low-dose (< 7.5 mg) long-term
      exposure (LD/LT-E); and medium-dose (> or = 7.5 mg) long-term exposure (MD/LT-E).
      The association of GC exposure with HT was evaluated using logistic regression
      analysis. RESULTS: HT was more prevalent in the MD/LT-E group (84.7%) than the
      LD/LT-E or N/L-E groups (70.7 and 67.3%, respectively, P = 0.028). Logistic
      regression revealed increased odds for HT when comparing MD/LT-E with N/L-E,
      after adjustment for HT risk factors [odds ratio (OR) = 2.57, 95% CI 1.01-6.56, P
      = 0.049] and RA disease characteristics (OR = 3.64, 95% CI: 1.36-9.77, P = 0.01).
      CONCLUSIONS: MD/LT GC exposure associates with a very high prevalence of HT. This
      appears to be independent of other risk factors for HT or of channelling bias due
      to disease severity, even though the latter cannot be excluded given the cross
      sectional nature of our study. RA patients in this GC exposure group should be
      particularly targeted for early identification and aggressive management of HT.

PMID- 18077494
TI  - Vasodilator iontophoresis a possible new therapy for digital ischaemia in
      systemic sclerosis?
AB  - OBJECTIVE: This study investigated whether whole finger vasodilator iontophoresis
      increases digital blood flow in patients with systemic sclerosis (SSc): If so,
      this might indicate a novel approach to therapy. METHODS: Eight patients and 8
      healthy controls underwent whole finger iontophoresis using a specially designed
      chamber. Treatment was with 0.5% sodium nitroprusside (NaNP) or 1% acetylcholine
      chloride (ACh), and the procedure then repeated with the other vasodilator
      (randomly assigned order). Three treatments were carried out for each chemical; 2
      min treatments were carried out bilaterally at 200 microA, a third was then
      carried out for 5 min on one digit only (randomly assigned to left or right).
      Blood flow increases were monitored with laser Doppler imaging (LDI). Maximum
      perfusion increase from baseline (MAX) and the area under the time perfusion
      curve (AUC), normalized for baseline, were calculated. Data were compared with a
      three-way analysis of variance test. RESULTS: Perfusion increased in both
      patients and controls, but significantly more so in controls (P(MAX) = 0.001,
      P(AUC) = 0.005, respectively). Values were significantly higher for the 5 min
      treatment compared with the 2 min treatment (P(MAX) = 0.011 and P(AUC) = 0.008
      for both groups). No significant differences were found between the use of NaNP
      and ACh. CONCLUSIONS: The increased perfusion with both ACh and NaNP in the
      patient group (albeit to a lesser degree than in the control group) indicates
      that this local approach to vasodilation is effective. Increasing iontophoresis
      time causes more sustained vasodilation. Further studies are indicated to
      investigate a possible therapeutic effect in patients with severe digital
      ischaemia.

PMID- 18077495
TI  - Cold stimulus fingertip lacticemy test--an effective method to monitor acute
      therapeutic intervention on primary Raynaud's phenomenon and systemic sclerosis.
AB  - OBJECTIVES: The recently developed cold stimulus fingertip lacticemy test (CS
      FTL) provides biochemical assessment of peripheral perfusion in patients with
      Raynaud's phenomenon (RP). We evaluated how the CS-FTL test can assess the acute
      effect of nifedipine in microvascular dynamics on primary RP and RP secondary to
      SSc. METHODS: A double-blinded controlled trial with crossover design was
      performed in 20 primary RP and 20 SSc patients. Patients received one single
      sublingual placebo or 10 mg nifedipine capsule, with crossover after a 15-day
      washout period. FTL was determined in resting conditions (pre-CS-FTL) and 10 min
      after CS (post-CS-FTL), before and 1 h after drug administration. Percent
      variation in post- vs pre-CS-FTL was expressed as deltaCS-FTL. RESULTS: Before
      intervention, CS induced FTL decrease in primary RP (deltaCS-FTL = -21.3 +/-
      13.0%) and FTL increase in SSc patients (deltaCS-FTL = +24.5 +/- 21.2%). Placebo
      had no effect on pre-CS-FTL, post-CS-FTL and deltaCS-FTL in primary RP and SSc.
      Nifedipine induced a significant decrease in pre-CS-FTL (1.94 +/- 0.45 vs 1.57 +/
      0.41 mg/dl; P = 0.005) and post-CS-FTL (1.53 +/- 0.35 vs 1.32 +/- 0.37 mg/dl; P
      = 0.004) in primary RP and a significant decrease in post-CS-FTL (3.18 +/- 1.43
      vs 2.56 +/- 1.30 mg/dl; P = 0.028) and deltaCS-FTL (+15.9 +/- 24.7% vs -12.9 +/-
      16.6%; P = 0.001) in SSc. CONCLUSIONS: The CS-FTL test was able to demonstrate
      and quantify a dual effect of nifedipine on the biochemical dimension of
      peripheral perfusion in primary RP and in SSc patients in which there was a
      significant improvement in tissue perfusion in resting conditions and after
      exposure to a CS. The CS-FTL test will enrich the armamentarium for investigation
      and clinical evaluation of conditions associated with RP.

PMID- 18077496
TI  - High-frequency ultrasound of skin involvement in systemic sclerosis reflects
      oedema, extension and severity in early disease.
AB  - OBJECTIVE: The aim was to compare skin assessment by palpation and by high
      frequency ultrasound in patients with SSc with disease duration <2 yrs. METHODS:
      Skin thickness and skin echogenicity were measured by 20 MHz ultrasound at five
      different anatomical sites in 106 individuals within 2 yrs from the first non
      Raynaud's symptom and compared with the modified Rodnan skin score (mRss).
      RESULTS: The patients with short disease duration were characterized by high skin
      thickness and low skin echogenicity, which correlated inversely, reflecting
      oedema. Patients with diffuse skin involvement displayed higher skin thickness
      and lower skin echogenicity than did patients with limited skin involvement. The
      ultrasound measurements correlated to the local mRss from the corresponding
      anatomical region and also to the total mRss. However, there was a considerable
      overlap in both skin thickness and skin echogenicity between different local mRss
      at all five anatomical sites. Skin involvement of the chest could be detected
      earlier by ultrasound than by palpation. CONCLUSION: In SSc patients with short
      disease duration, high-frequency ultrasound can identify the oedematous phase
      that may precede palpable skin involvement and may thus be useful to identify
      patients with diffuse skin involvement very early in the disease process.
      Ultrasound measurements also reflect the severity of the overall skin
      involvement.

PMID- 18077497
TI  - The epidemiology of total knee replacement in South Korea: national registry
      data.
AB  - OBJECTIVE: Knee osteoarthritis (OA) is prevalent among the elderly in Asian
      countries; however, the utilization of total knee replacement (TKR) is unknown.
      Using data from a national registry, we sought to estimate the incidence of TKR
      by age and sex, and the trend for TKR utilization from 2002 to 2005 in South
      Korea. METHODS: Reimbursement records from all hospitals in South Korea were
      extracted from the Health Insurance Review Agency (HIRA) database. Records with
      both the procedure code corresponding to a TKR and the diagnosis code of knee OA
      were selected. We estimated the age- and sex-specific rates of TKR. To compare
      the rate of TKR between men and women, we calculated age-standardized risk
      ratios. A TKR registry from a single centre containing more clinical information
      was analysed, and the differences in the clinical features between men and women
      were compared. RESULTS: From 2002 to 2005, 47 961 TKRs were performed in subjects
      over the age of 40 yrs due to OA. The rate of TKR has increased over the 4 yrs
      and was much higher in women than in men. Compared with men, the age-standardized
      rate ratios for TKR in women ranged from 7.4 to 8.0. The single-centre registry
      data revealed that there was no difference in age, disease duration and the
      Kellgren-Lawrence grade at the time of surgery between men and women. CONCLUSION:
      Using a national database, we found that the rate of TKR increased steadily from
      2002 to 2005 in South Korea. The TKR rate in women was much higher than that in
      men. Risk factors that account for such disparity in TKR utilization need to be
      further investigated.

PMID- 18077498
TI  - MRI changes in psoriatic dactylitis--extent of pathology, relationship to
      tenderness and correlation with clinical indices.
AB  - OBJECTIVES: To quantify the extent of inflammation in psoriatic dactylitis and to
      examine the relationship between clinical and magnetic resonance imaging (MRI)
      data in both tender and non-tender dactylitis. METHODS: Seventeen patients with
      psoriatic dactylitis underwent clinical assessment for 6 months after change of
      treatment, usually to methotrexate. Measures of dactylitis included the Leeds
      Dactylitis Index, the assessment tool used in the Infliximab in Psoriatic
      Arthritis Clinical Trial (IMPACT), a simple count of tender dactlylitic digits
      and a count of all dactylitic digits, both tender and non-tender. MRI scans of
      the affected hand or foot were performed before and after treatment using a 1.5T
      Siemen's scanner pre- and post-contrast. RESULTS: All patients improved
      clinically, as did their respective dactylitis scores and MRI images. The
      findings on MRI in both dactylitic and non-dactylitic digits were profound and
      widespread. The difference between tender and non-tender dactylitis was
      quantitative rather than qualitative. Synovitis and soft-tissue oedema were the
      most frequent abnormalities being present in 69% of tender dactylitic digits but
      bone oedema and flexor tenosynovitis were also frequently seen. Soft-tissue
      oedema was circumferential and enhancing and not limited to association with the
      flexor or extensor tendons. None of the clinical indices of dactylitis showed a
      close relationship to the extent of MRI abnormalities. CONCLUSIONS: MRI images
      demonstrate widespread abnormalities in digits of people with psoriatic
      arthritis. Tender dactylitic digits have more abnormalities than other digits but
      the relationship between clinical and MRI scores is not strong.

PMID- 18077499
TI  - Ultrasound of proximal upper extremity arteries to increase the diagnostic yield
      in large-vessel giant cell arteritis.
AB  - OBJECTIVE: To describe characteristic ultrasound findings and clinical features
      of patients with newly diagnosed cranial and large-vessel (LV) GCA in a
      specialized ultrasound clinic. METHODS: This case-control study includes all
      consecutive patients between 1997 and 2006 with newly diagnosed GCA. Duplex
      ultrasound of the temporal, subclavian, axillary and proximal brachial arteries
      was performed in all patients with suspected temporal arteritis, PMR, arm
      claudication, unclear inflammation or pyrexia of unknown origin (PUO). RESULTS:
      In 53 of 176 patients, ultrasound depicted characteristic vasculitic homogeneous
      wall swelling of the axillary, subclavian and/or proximal brachial arteries.
      These were affected in 98, 61 and 21%, respectively, in the 53 patients. The
      findings were bilateral in 79%. Axillary arteries were stenotic or occluded in 51
      and 2% and temporal artery ultrasound and histology were positive in 62 and 67%
      of LV-GCA cases, respectively. A significantly greater number of LV-GCA patients
      were female (83 vs 65%) and younger (mean 66 vs 72 yrs) as compared with those
      without proximal arm involvement. Headaches (38 vs 75%), jaw claudication (24 vs
      48%) and anterior ischaemic optic neuropathy (4 vs 19%) occurred significantly
      less frequently. The median time until diagnosis was significantly longer (31 vs
      8 weeks). ESR and presence of PMR were similar in both groups. CONCLUSIONS:
      Performing axillary artery ultrasound in all patients with suspected temporal
      arteritis, PMR, arm claudication, unclear inflammation or PUO increases the
      diagnostic yield for LV-GCA. Patients with LV-GCA differ from those without arm
      involvement.

PMID- 18077500
TI  - Comment on: Arthritis as presenting manifestation of pure neuritic leprosy--a
      rheumatologist's dilemma.

PMID- 18077501
TI  - Comment on: Guidelines for the management of the hot swollen joint in adults.

PMID- 18077504
TI  - Systemic mediastinal lymph node dissection of right lung cancer: surgical quality
      control and analysis of mediastinal lymph node metastatic patterns.
AB  - Standardization of systemic mediastinal lymph node dissection (SMLD) of lung
      cancer requires further investigation. A consecutive 124 right lung cancer
      patients were recruited for pulmonary resection plus SMLD. Three mediastinal
      lymph node compartments, (i) the upper compartment (station 1-4), (ii) the middle
      compartment (station 7-8) and (iii) the lower compartment (station 9), were en
      bloc collected to achieve surgical quality control and to analyze mediastinal
      lymph node metastatic patterns. The number of total harvested lymph nodes, N1
      nodes and N2 nodes were 21.9+/-8.7, 9.2+/-4.7 and 12.8+/-6.7, respectively. Tumor
      location (peripheral or central) (P=0.023) and status of blood vessel invasion
      (P=0.002) were identified as risk factors for nodal involvement. Right upper lobe
      (RUL) cancer with N2 disease primarily metastasized to the upper compartment
      (27.3%) (P=0.001). For right lower lobe (RLL) cancer, lymph node metastasis most
      commonly detected in the middle compartment (48.8%) (P=0.001). Single mediastinal
      compartment metastasis occurred in 64.7% (11/17) of adenocarcinomas from RUL and
      RML, whereas multiple compartments metastasis occurred in all adenocarcinoma
      cases (12/12) from RLL (P=0.001). SMLD needs to standardize the extent of
      lymphadenectomy and number of removed lymph nodes for surgical quality control.
      Simplifying mediastinal lymph node stations to three compartments may benefit
      surgical excision.

PMID- 18077505
TI  - Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice.
      A potential renoprotective mechanism.
AB  - OBJECTIVE: an increased glomerular filtration rate (GFR) has been postulated as a
      potential mechanism involved in the progression of diabetic nephropathy. Studies
      suggest that C-peptide exerts a renoprotective effect on diabetes. The peptide
      decreases hyperfiltration in patients with type 1 diabetes, as well as in
      diabetic animal models. In this study, we investigated whether C-peptide causes a
      change in arteriolar diameter. RESEARCH DESIGN AND METHODS: C57-Bl mice were made
      diabetic by means of a single intravenous injection of alloxan 2 wk prior to the
      experiment. Age-matched normoglycemic mice served as controls. Afferent
      arterioles, intact with the glomeruli, were dissected and microperfused. The
      effect of luminal application of C-peptide, compared with scrambled C-peptide or
      vehicle, was investigated. The effect of the Rho-kinase inhibitor Y-27632 was
      also investigated. RESULTS: C-peptide constricted afferent arterioles in diabetic
      mice by -27% compared with the control value. Normoglycemic arterioles
      administered C-peptide displayed a delayed and minute response (-4%). Scrambled C
      peptide or vehicle administration, whether administered to hyperglycemic or
      normoglycemic mice, did not induce any effect. Addition of Y-27632 abolished the
      effect of C-peptide. CONCLUSION: C-peptide induces constriction of afferent
      arterioles in diabetic mice. This can reduce enhanced GFR and may be one of the
      mechanisms in the renoprotective action of C-peptide in diabetes.

PMID- 18077506
TI  - Taste-responsive neurons in the nucleus of the solitary tract receive gustatory
      information from both sides of the tongue in the hamster.
AB  - Taste receptors on the left and right sides of the anterior tongue are innervated
      by chorda tympani (CT) fibers, which carry taste information to the ipsilateral
      nucleus of the solitary tract (NST). Although the anterior tongue is essential
      for taste, patients with unilateral CT nerve damage often report no subjective
      change in their taste experience. The standing theory that explains the taste
      constancy is the "release of inhibition", which hypothesizes that within the NST
      there are inhibitory interactions between inputs from the CT and glossopharyngeal
      nerves and that the loss of taste information from the CT is compensated by a
      release of inhibition on the glossopharyngeal nerve input. However, the
      possibility of compensation by taste input from the other side of the tongue has
      never been investigated in rodents. We recorded from 95 taste-responsive neurons
      in the NST and examined their responsiveness to stimulation of the contralateral
      CT. Forty-six cells were activated, mostly with excitatory responses (42 cells).
      Activation of NST cells induced by contralateral CT stimulation was blocked by
      microinjection of lidocaine into the contralateral NST but was not affected by
      anesthetization of the contralateral parabrachial nuclei (PbN). In addition, the
      NST cells that were activated by contralateral CT stimulation showed reduced
      responsiveness to taste stimulation after microinjection of lidocaine into the
      contralateral NST. These results demonstrate that nearly half of the taste
      neurons in the NST receive gustatory information from both sides of the tongue.
      This "cross talk" between bilateral NST may also contribute to the "taste
      constancy".

PMID- 18077507
TI  - Development of the corticosteroid stress axis and receptor expression in
      zebrafish.
AB  - Using zebrafish embryos and larvae, we examined the temporal patterns of cortisol
      and expression of genes involved in corticosteroid synthesis and signaling.
      Embryonic cortisol levels decreased approximately 70% from 1.5 h
      postfertilization (hpf) to hatch (approximately 42 hpf) and then increased 27
      fold by 146 hpf. The mRNA abundances of steroidogenic acute regulatory protein,
      11beta-hydroxylase and 11beta-hydroxysteroid dehydrogenase type 2, increased
      severalfold after hatch and preceded the rise of cortisol levels. In contrast to
      other teleosts that possess two glucocorticoid receptors (GRs) and one
      mineralocorticoid receptor (MR), only one GR and MR were identified in zebrafish,
      which were cloned and sequenced. GR mRNA abundance decreased from 1.5 to 25 hpf,
      rebounded, and then was stable from 49 to 146 hpf. MR transcripts increased
      continuously from 1.5 hpf and were 52-fold higher by 97 hpf. An acute cortisol
      response to a stressor was not detected until 97 hpf, whereas melanocortin type 2
      receptor mRNA increased between 25 and 49 hpf. Collectively, the patterns of
      cortisol and the expression of cortisol biosynthetic genes and melanocortin type
      2 receptor suggest that the corticoid stress axis in zebrafish is fully developed
      only after hatch. The temporal differences in GR, MR, and 11beta-hydroxysteroid
      dehydrogenase type 2 gene expression lead us to propose a key role for MR
      signaling by maternal cortisol during embryogenesis, whereas cortisol secretion
      after hatch may be regulating GR expression and signaling in zebrafish.

PMID- 18077508
TI  - Genetic variation in Glp1r expression influences the rate of gastric emptying in
      mice.
AB  - We demonstrated previously that food intake traits map to a quantitative trait
      locus (QTL) on proximal chromosome 17, which encompasses Glp1r (glucagon-like
      peptide 1 receptor), encoding an important modulator of gastric emptying. We then
      confirmed this QTL in a B6.CAST-17 congenic strain that consumed 27% more
      carbohydrate and 17% more total calories, yet similar fat calories, per body
      weight compared with the recipient C57BL/6J. The congenic strain also consumed
      greater food volume. The current aims were to 1) identify genetic linkage for
      total food volume in F(2) mice, 2) perform gene expression profiling in stomach
      of B6.CAST-17 congenic mice using oligonucleotide arrays, 3) test for allelic
      imbalance in Glp1r expression, 4) evaluate gastric emptying rate in parental and
      congenic mice, and 5) investigate a possible effect of genetic variation in Glp1r
      on gastric emptying. A genome scan revealed a single QTL for total food volume
      (Tfv1) (log of the odds ratio = 7.6), which was confirmed in B6.CAST-17 congenic
      mice. Glp1r exhibited allelic imbalance in stomach, which correlated with
      accelerated gastric emptying in parental CAST and congenic B6.CAST-17 mice.
      Moreover, congenic mice displayed an impaired gastric emptying response to
      exendin-(9-39). These results suggest that genetic variation in Glp1r contributes
      to the strain differences in gastric emptying rate.

PMID- 18077509
TI  - Functional topography of the dorsomedial hypothalamus.
AB  - The dorsomedial hypothalamus (DMH) has been proposed to play key roles in both
      the defense reaction to acute stress and in the thermoregulatory response to
      cold. We reasoned that the autonomic/respiratory motor patterns of these
      responses would be mediated by at least partly distinct DMH neuron populations.
      To test this, we made simultaneous recordings of phrenic nerve and plantar
      cutaneous vasoconstrictor (CVC) activity in 14 vagotomized, ventilated, urethane
      anesthetized rats. Microinjections of d,l-homocysteic acid (DLH; 15 nl, 50 mM)
      were used to cause localized, short-lasting (<1 min) activation of DMH neuron
      clusters. Cooling the rat's trunk skin by perfusing cold water through a water
      jacket-activated plantar CVC activity but depressed phrenic burst rate (cold
      response pattern). The expected "stress/defense response" pattern would be
      phrenic activation, with increased blood pressure, heart rate, and possibly CVC
      activity. DLH microinjections into 76 sites within the DMH region never reduced
      phrenic activity. They frequently increased phrenic rate and/or plantar CVC
      activity, but the magnitudes of those two responses were not significantly
      correlated. Plantar CVC responses were evoked most strongly from the dorsal
      hypothalamic area and most dorsal part of the dorsomedial nucleus, whereas peak
      phrenic rate responses were evoked from more caudal sites; their relative
      magnitudes varied systematically with rostrocaudal position. Tachycardia
      correlated with plantar CVC responses but not phrenic rate. These findings
      indicate that localized activation of DMH neurons does not evoke full "cold
      response" or stress/defense response patterns, but they demonstrate the existence
      of significant functional topography within the DMH region.

PMID- 18077510
TI  - Effects of uteroplacental insufficiency and reducing litter size on maternal
      mammary function and postnatal offspring growth.
AB  - Human intrauterine growth restriction is often associated with uteroplacental
      insufficiency and a decline in nutrient and oxygen supply to the fetus. This
      study investigated the effects of uteroplacental insufficiency and intrauterine
      growth restriction (Restricted) or reducing litter size for normally grown pups
      (Reduced Litter) on maternal mammary development and function, milk composition,
      offspring milk intake, and their resultant effects on postnatal growth.
      Uteroplacental insufficiency was surgically induced by bilateral uterine vessel
      ligation on day 18 of gestation in the Wistar Kyoto rat. At birth, a group of
      sham control rats had their litter size reduced to five (Reduced Litter) to match
      that of the Restricted group. Cohorts of rats were terminally anesthetized on day
      20 of gestation or day 6 of lactation, and a third group was studied throughout
      lactation. Restricted pups had a lower birth weight (by 16%) and litter size (by
      36%) compared with controls, as well as reduced mammary parathyroid hormone
      related protein content and milk ionic calcium concentrations associated with
      reduced total pup calcium. Restricted dams with lower circulating progesterone
      experienced premature lactogenesis, producing less milk per pup with altered
      composition compared with controls, further slowing growth during lactation.
      Reducing litter size of pups born of normal birth weight (Reduced Litter) was
      associated with decreased pup growth, highlighting the importance of appropriate
      controls. The present study demonstrates that uteroplacental insufficiency
      impairs mammary function, compromises milk quality and quantity, and reduces
      calcium transport into milk, further restraining postnatal growth.

PMID- 18077511
TI  - Inhibition of shortening velocity of skinned skeletal muscle fibers in conditions
      that mimic fatigue.
AB  - The mechanisms responsible for the inhibition of shortening velocity that occurs
      during muscle fatigue have not been completely elucidated. Phosphorylation of the
      myosin regulatory light chain (RLC) occurs during heavy use; however, previous
      reports on its role in affecting velocity have been equivocal. To further
      understand the process of fatigue, we varied the levels of myosin RLC
      phosphorylation (from 10 to >50%) and the concentrations of protons (from pH 7 to
      6.2) and phosphate (from 5 to 30 mM), all of which change during fatigue. We
      measured the mechanics of permeable rabbit psoas fibers at a temperature closer
      to physiological (30 degrees C), using a temperature jump protocol to briefly
      activate the fibers at the higher temperature to preserve sarcomere homogeneity.
      Although lowered pH alone had an effect on velocity, it was the three factors
      together, i.e., high phosphorylation, low pH, and high phosphate, that acted
      synergistically to inhibit fiber velocity by approximately 40%. Our data
      demonstrate that in conditions that simulate physiological muscle fatigue, myosin
      phosphorylation does contribute to the inhibition of contraction velocity of
      fully activated fast muscle fibers.

PMID- 18077512
TI  - Hippocampal mitochondrial dysfunction in rat aging.
AB  - Hippocampus mitochondrial dysfunction with impaired electron transfer and
      increased oxidative damage was observed upon rat aging. Hippocampal mitochondria
      of aged (12 mo) and senescent (20 mo) rats showed, compared with young (4 mo)
      rats, marked decreases in the rate of state 3 respiration with NAD-dependent
      substrates (32-51%) and in the activities of mitochondrial complexes I (57-73%)
      and IV (33-54%). The activity of mitochondrial nitric oxide synthase was also
      decreased, 53-66%, with age. These losses in enzymatic activity were more marked
      in the hippocampus than in brain cortex or in whole brain. The histochemical
      assay of mitochondrial complex IV in the hippocampus showed decreased staining
      upon aging. Oxidative damage, determined as the mitochondrial content of
      thiobarbituric-acid reactive substances (TBARS) and protein carbonyls, increased
      in aged and senescent hippocampus (66-74% in TBARS and 48-96% in carbonyls). A
      significant statistical correlation was observed between mitochondrial oxidative
      damage and enzymatic activity. Mitochondrial dysfunction with shortage of energy
      supply is considered a likely cause of dysfunction in aged hippocampus.

PMID- 18077513
TI  - Role of pudendal afferents in voiding efficiency in the rat.
AB  - The reciprocal activities of the bladder and external urethral sphincter (EUS)
      are coordinated by descending projections from the pontine micturition center but
      are subjected to modulation by peripheral afferent inputs. Transection of the
      somatic pudendal nerve innervating the striated EUS decreases voiding efficiency
      and increases residual urine in the rat. The reduction in voiding efficiency was
      attributed to the lack of phasic bursting activity of the EUS following
      denervation. However, transection of the pudendal nerve also eliminates somatic
      sensory feedback that may play a role in voiding. We hypothesized that feedback
      from pudendal afferents is required for efficient voiding and that the loss of
      pudendal sensory activity contributes to the observed reduction in voiding
      efficiency following pudendal nerve transection. Quantitative cystometry in
      urethane anesthetized female rats following selective transection of pudendal
      nerve branches, following chemical modulation of urethral afferent activity, and
      following neuromuscular blockade revealed that pudendal nerve afferents
      contributed to efficient voiding. Sensory feedback augmented bladder contraction
      amplitude and duration, thereby increasing the driving force for urine expulsion.
      Second, sensory feedback was necessary to pattern appropriately the EUS activity
      into alternating bursts and quiescence during the bladder contraction. These
      findings demonstrate that the loss of pudendal sensory activity contributes to
      the reduction in voiding efficiency observed following pudendal nerve
      transection, and illustrate the importance of urethral sensory feedback in
      regulating bladder function.

PMID- 18077514
TI  - Cortisol stimulates the zinc signaling pathway and expression of metallothioneins
      and ZnT1 in rainbow trout gill epithelial cells.
AB  - Intracellular zinc signaling is important in the control of a number of cellular
      processes. Hormonal factors that regulate cellular zinc influx and initiate zinc
      signals are poorly understood. The present study investigates the possibility for
      cross talk between the glucocorticoid and zinc signaling pathways in cultured
      rainbow trout gill epithelial cells. The rainbow trout metallothionein A (MTA)
      gene possesses a putative glucocorticoid response element and multiple metal
      response elements 1042 base pairs upstream of the start codon, whereas
      metallothionein B (MTB) and zinc transporter-1 (ZnT1) have multiple metal
      response elements but no glucocorticoid response elements in this region.
      Cortisol increased MTA, MTB, and ZnT1 gene expression, and this stimulation was
      enhanced if cells were treated with cortisol together with zinc. Cells treated
      with zinc showed increased zinc accumulation, transepithelial zinc influx (apical
      to basolateral), and intracellular labile zinc concentrations. These responses
      were also significantly enhanced in cells pretreated with cortisol and zinc. The
      cortisol-mediated effects were blocked by the glucocorticoid receptor (GR)
      antagonist RU-486, indicating mediation via a GR. In reporter gene assays, zinc
      stimulated MTA promoter activity, whereas cortisol did not. Furthermore, cortisol
      significantly reduced zinc-stimulated MTA promoter activity in cells expressing
      exogenous rainbow trout GR. These results demonstrate that cortisol enhances
      cellular zinc uptake, which in turn stimulates expression of MTA, MTB, and ZnT1
      genes.

PMID- 18077515
TI  - Chorionic enhancer is dispensable for regulated expression of the human renin
      gene.
AB  - We tested the hypothesis that a transcriptional chorionic enhancer (CE),
      previously identified to increase human renin expression in choriodecidual cells
      is required to mediate tissue-specific, cell-specific, and regulated expression
      of human renin in transgenic mice. Recombineering was used to delete the CE
      upstream of the renin gene alone or in combination with the kidney enhancer (KE)
      in a large artificial chromosome construct containing the entire human renin gene
      and extensive flanking sequences. Deletion of the CE had no qualitative or
      quantitative effect on the tissue-specific expression of human renin, nor on the
      cellular localization of human renin in the kidney or placenta. Combined deletion
      of both the CE and KE caused a decrease in the level of renal renin expression
      consistent with the established role of the KE. We also considered the
      possibility that the CE is a downstream enhancer of the KiSS1 gene, which lies
      directly upstream of renin and is also expressed in the placenta. Deletion of the
      CE alone, or the CE and KE together, had no effect on the level of KiSS1
      expression in the placenta. These data provide convincing evidence that the CE is
      silent in vivo, at least in the mouse. The absence of a phenotype caused by
      deletion of the CE is consistent with the observation that the sequence is not
      evolutionarily conserved.

PMID- 18077516
TI  - Inhalation of the ETA receptor antagonist LU-135252 selectively attenuates
      hypoxic pulmonary vasoconstriction.
AB  - Endogenous endothelin (ET)-1 modulates hypoxic pulmonary vasoconstriction (HPV).
      Accordingly, intravenously applied ET(A) receptor antagonists reduce HPV, but
      this is accompanied by systemic vasodilation. We hypothesized that inhalation of
      an ET(A) receptor antagonist might act selectively on the pulmonary vasculature
      and investigated the effects of aerosolized LU-135252 in an experimental model of
      HPV. Sixteen piglets (weight: 25 +/- 1 kg) were anesthetized and mechanically
      ventilated at an inspiratory oxygen fraction (Fi(O(2))) of 0.3. After 1 h of
      hypoxia at Fi(O(2)) 0.15, animals were randomly assigned either to receive
      aerosolized LU-135252 as bolus (0.3 mg/kg for 20 min; n = 8, LU group), or to
      receive aerosolized saline (n = 8, controls). In all animals, hypoxia
      significantly increased mean pulmonary arterial pressure (32 +/- 1 vs. 23 +/- 1
      mmHg; P < 0.01; means +/- SE) and increased arterial plasma ET-1 (0.52 +/- 0.04
      vs. 0.37 +/- 0.05 fmol/ml; P < 0.01) compared with mild hyperoxia at Fi(O(2))
      0.3. Inhalation of LU-135252 induced a significant and sustained decrease in mean
      pulmonary arterial pressure compared with controls (LU group: 27 +/- 1 mmHg;
      controls: 32 +/- 1 mmHg; values at 4 h of hypoxia; P < 0.01). In parallel, mean
      systemic arterial pressure and cardiac output remained stable and were not
      significantly different from control values. Consequently, in our experimental
      model of HPV, the inhaled ET(A) receptor antagonist LU-135252 induced selective
      pulmonary vasodilation without adverse systemic hemodynamic effects.

PMID- 18077517
TI  - CELLDOSE: a Monte Carlo code to assess electron dose distribution--S values for
      131I in spheres of various sizes.
AB  - Monte Carlo simulation can be particularly suitable for modeling the microscopic
      distribution of energy received by normal tissues or cancer cells and for
      evaluating the relative merits of different radiopharmaceuticals. We used a new
      code, CELLDOSE, to assess electron dose for isolated spheres with radii varying
      from 2,500 mum down to 0.05 mum, in which (131)I is homogeneously distributed.
      METHODS: All electron emissions of (131)I were considered, including the whole
      beta(- 131)I spectrum, 108 internal conversion electrons, and 21 Auger electrons.
      The Monte Carlo track-structure code used follows all electrons down to an energy
      threshold E(cutoff) = 7.4 eV. RESULTS: Calculated S values were in good agreement
      with published analytic methods, lying in between reported results for all
      experimental points. Our S values were also close to other published data using a
      Monte Carlo code. Contrary to the latter published results, our results show that
      dose distribution inside spheres is not homogeneous, with the dose at the outmost
      layer being approximately half that at the center. The fraction of electron
      energy retained within the spheres decreased with decreasing radius (r): 87.1%
      for r = 2,500 mum, 8.73% for r = 50 mum, and 1.18% for r = 5 mum. Thus, a
      radioiodine concentration that delivers a dose of 100 Gy to a micrometastasis of
      2,500 mum radius would deliver 10 Gy in a cluster of 50 mum and only 1.4 Gy in an
      isolated cell. The specific contribution from Auger electrons varied from 0.25%
      for the largest sphere up to 76.8% for the smallest sphere. CONCLUSION: The dose
      to a tumor cell will depend on its position in a metastasis. For the treatment of
      very small metastases, (131)I may not be the isotope of choice. When trying to
      kill isolated cells or a small cluster of cells with (131)I, it is important to
      get the iodine as close as possible to the nucleus to get the enhancement factor
      from Auger electrons. The Monte Carlo code CELLDOSE can be used to assess the
      electron map deposit for any isotope.

PMID- 18077518
TI  - Cortical flattening applied to high-resolution 18F-FDG PET.
AB  - Group studies using PET and other types of neuroimaging require some means to
      achieve congruence of brain structures across subjects, such that scans from
      individuals varying in brain shape and gyral anatomy can be analyzed together.
      Volume registration methods are the most widely used approach to achieve this
      congruence. They are fast and typically require little manual interaction, but,
      unfortunately, it is difficult to achieve a good match between cortical areas in
      volume space, especially where folding patterns vary across subjects. Cortical
      flattening is a recent, alternative strategy: Its key features are explicit
      definition of cortex, such that white matter or cerebrospinal fluid compartments
      are largely excluded from the analysis volume, and subsequent registration of the
      cortical sheet in its natural, 2-dimensional topology. This type of registration
      has been demonstrated to provide better matching of congruent cortical structures
      than volume methods and, thus, offers a potentially more robust way of analyzing
      PET data. METHODS: Here, we explore the applicability of cortical flattening of
      coregistered MRI to (18)F-FDG PET on the HRRT system (high-resolution research
      tomograph), the highest-resolution whole-head scanner available to date. RESULTS:
      We report average values and SD of cortical metabolism in a pilot study of the
      dominant hemisphere in 9 control subjects and provide estimates of group sizes
      necessary for studies using this technique. CONCLUSION: We conclude that cortical
      flattening with subsequent surface registration is a feasible and promising
      strategy for group studies on the HRRT, providing the highest fidelity maps of
      human cortical glucose consumption to date.

PMID- 18077519
TI  - In vivo imaging of 64Cu-labeled polymer nanoparticles targeted to the lung
      endothelium.
AB  - Nanoparticles (NPs) targeting the intercellular adhesion molecule 1 (ICAM-1) hold
      promise as a mean of delivering therapeutics to the pulmonary endothelium in
      patients with acute and chronic respiratory diseases. As these new materials
      become available, strategies are needed to understand their behavior in vivo. We
      have evaluated the use of (64)Cu and PET to noninvasively image the lung uptake
      and distribution of NPs coated with an anti-ICAM antibody. METHODS: Model
      fluorescent NPs were coated with a mixture of an anti-ICAM antibody (or
      nonspecific IgG) and (64)Cu-DOTA-IgG (where DOTA is 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid). Biodistribution and small
      animal PET and CT studies were performed in healthy mice and in mice pretreated
      with lipopolysaccharides (LPSs). Metabolism studies were also performed to
      evaluate the stability of (64)Cu-labeled NPs in lungs in vivo. RESULTS: The lungs
      of mice administered anti-ICAM NPs labeled with (64)Cu were clearly imaged by
      small-animal PET 1, 4, and 24 h after administration. Both biodistribution and
      small-animal imaging showed a 3- to 4-fold higher uptake in the lungs of mice
      injected with ICAM-targeted NPs relative to that of the control group. Lung
      uptake was further enhanced by pretreating the mice with LPS, presumably because
      of ICAM-1 upregulation. However, an approximately 2-fold decrease in lung signal
      was observed in each experimental group over 24 h. Metabolism studies in lung
      tissues harvested from mice injected with (64)Cu-labeled anti-ICAM NPs showed
      considerable release of a small (64)Cu-radiometabolite from the NPs beginning as
      early as 1 h after injection. A decrease in lung fluorescence was also observed,
      most likely reflecting partial release of NPs from the lungs in vivo. CONCLUSION:
      The use of small-animal PET to track (64)Cu-labeled nanostructures in vivo shows
      potential as a strategy for the preclinical screening of new NP drug delivery
      agents targeting the lung endothelium and other tissues. Future design
      optimization to prolong the stability of the radiolabel in vivo will further
      improve this promising approach.

PMID- 18077520
TI  - Cochlear implant benefits in deafness rehabilitation: PET study of temporal voice
      activations.
AB  - Cochlear implants may improve the medical and social prognosis of profound
      deafness. Nevertheless, some patients have experienced poor results without any
      clear explanations. One correlate may be an alteration in cortical voice
      processing. To test this hypothesis, we studied the activation of human temporal
      voice areas (TVA) using a well-standardized PET paradigm adapted from previous
      functional MRI (fMRI) studies. METHODS: A PET H(2)(15)O activation study was
      performed on 3 groups of adult volunteers: normal-hearing control subjects (n =
      6) and cochlear-implanted postlingually deaf patients with >2 y of cochlear
      implant experience, with intelligibility scores in the "Lafon monosyllabic task"
      >80% (GOOD group; n = 6) or <20% (POOR group; n = 6). Relative cerebral blood
      flow was measured in 3 conditions: rest, passive listening to human voice, and
      nonvoice stimuli. RESULTS: Compared with silence, the activations induced by
      nonvoice stimuli were bilaterally located in the superior temporal regions in all
      groups. However these activations were significantly and similarly reduced in
      both cochlear implant groups, whereas control subjects showed supplementary
      activations. Compared with nonvoice, the voice stimuli induced bilateral
      activation of the TVA along the superior temporal sulcus (STS) in both the
      control and the GOOD groups. In contrast, these activations were not detected in
      the POOR group, which showed only left unilateral middle STS activation.
      CONCLUSION: These results suggest that PET is an adequate method to explore
      cochlear implant benefits and that this benefit could be linked to the activation
      of the TVA.

PMID- 18077521
TI  - Probabilistic anatomic mapping of cerebral blood flow distribution of the middle
      cerebral artery.
AB  - Probabilistic atlases are more representative of the population than single brain
      atlases. They allow anatomic and functional labeling of the results of group
      studies in stereotactic space and, hence, the automated anatomic labeling of
      individual brain imaging data. METHODS: In the current study, probabilistic maps
      of the blood flow distribution of the middle cerebral artery (MCA) were developed
      using the basal and MCA brain SPECT images. Twenty-nine patients (mean age +/-
      SD, 54.6 +/- 6.1 y) who previously received placement of a stent for MCA stenosis
      (right MCA stenosis, 15 patients; left MCA stenosis, 14 patients) were included
      in the current study. Of the 29 MCA SPECT images, 18 were analyzed for the final
      result because 11 MCA SPECT images revealed an uneven uptake distribution of
      (99m)Tc-ethylcysteinate dimer in the brain. MCA brain SPECT images were
      coregistered to basal brain SPECT images, and spatial normalization parameters
      used for basal brain SPECT images were reapplied to MCA brain SPECT for anatomic
      standardization. Pixel counts of the MCA brain SPECT images were then normalized,
      and the probabilistic map of cerebral perfusion distribution (perfusion
      probabilistic map) for each hemisphere was determined by averaging the spatial-
      and count-normalized MCA brain SPECT images. Population-based probabilistic maps
      representing the extent of MCA territory (extent probabilistic map) were also
      composed by averaging the binary images obtained by thresholding the spatially
      normalized MCA brain SPECT images. RESULTS: The blood supply from the MCA to the
      basal ganglia area was largest (probability, 0.6 approximately 0.8), followed by
      the insular cortex (probability, 0.3 approximately 0.5), and various cerebral
      cortical areas (probability, 0.2 approximately 0.4). The MCA reached to deep
      structures of the brain, including the internal capsule, caudate nucleus,
      putamen, globus pallidus, insular cortex, and thalamus with a high-extent
      probability. CONCLUSION: A population-based probabilistic map of MCA flow
      distribution was generated by using MCA brain SPECT images. This map could be a
      potential tool for the analysis of major cerebral artery distribution, especially
      the MCA. Furthermore, the probabilistic MCA atlas could be used to define the
      object delineation of the MCA territory, to quantify ischemic disease affecting
      the MCA, to predict prognosis, and to risk stratification of cerebrovascular
      diseases, especially affecting the MCA.

PMID- 18077522
TI  - 18F-FDG PET as a routine test for posttherapy assessment of Hodgkin's disease and
      aggressive non-Hodgkin's lymphoma: where is the evidence?

PMID- 18077523
TI  - Generation of destabilized herpes simplex virus type 1 thymidine kinase as
      transcription reporter for PET reporter systems in molecular genetic imaging.
AB  - Herpes simplex virus type 1 thymidine kinase (HSV1-TK) is a widely used reporter
      for in vivo noninvasive monitoring of therapeutic gene expression, immune cell
      trafficking, and protein-protein interactions in various animal systems. However,
      the stability of HSV1-TK limits its application in studies that require rapid
      turnover of the reporter. The purpose of this study was to create a destabilized
      HSV1-TK as a transcription reporter that allows for dynamic studies of short-time
      scale gene expression events. METHODS: A destabilized HSV1-TK was created by
      targeting inactivating mutations in the nuclear localization signal of HSV1-TK
      and fusing the degradation domain of mouse ornithine decarboxylase to the C
      terminal end. The protein or enzyme stability was determined by Western blot
      analysis and HSV1-TK enzyme activity assay, respectively. The proteasome
      inhibition assay was used to test whether the rapid turnover of the destabilized
      HSV1-TK was processed in a 26S proteasome-dependent manner. The suitability of
      destabilized HSV1-TK as a transcription reporter was tested by linking it to a
      tetracycline-turnoff-expressing system. The dynamic transcriptional events
      mediating a series of doxycycline inductions were monitored by destabilized HSV1
      TK or by native HSV1-TK and were determined by an in vitro HSV1-TK enzyme
      activity assay and in vivo small-animal PET imaging. RESULTS: The destabilized
      HSV1-TK, unlike wild-type HSV1-TK, was unstable in the presence of cycloheximide
      and had a short half-life of protein and enzyme activity. The rapid turnover of
      the destabilized HSV1-TK was processed in a 26S proteasome-dependent manner.
      Furthermore, the destabilized HSV1-TK had low cytotoxicity when it was highly
      expressed in living cells. The results of dynamic gene expression studies in
      vitro and in vivo showed that the destabilized HSV1-TK is an optimal reporter for
      monitoring short-time-scale dynamic transcriptional events mediating a series of
      doxycycline inductions, whereas the wild-type HSV1-TK is not optimal to achieve
      this purpose. CONCLUSION: The use of destabilized HSV1-TK as a transcription
      reporter together with a molecular probe, which has a short physical and biologic
      half-life, allows more direct monitoring of transcription induction and easier
      monitoring of its coincidence with other biochemical changes.

PMID- 18077524
TI  - Don't bury the V/Q scan: it's as good as multidetector CT angiograms with a lot
      less radiation exposure.

PMID- 18077525
TI  - Usefulness of 11C-methionine for differentiating tumors from granulomas in
      experimental rat models: a comparison with 18F-FDG and 18F-FLT.
AB  - Many clinical PET studies have shown that increased (18)F-FDG uptake is not
      specific to malignant tumors. (18)F-FDG is also taken up in inflammatory lesions,
      particularly in granulomatous lesions such as sarcoidosis or active inflammatory
      processes after chemoradiotherapy, making it difficult to differentiate malignant
      tumors from benign lesions, and is the main source of false-positive (18)F-FDG
      PET findings in oncology. These problems may be overcome by multitracer studies
      using 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) or l-(11)C-methionine.
      However, (18)F-FLT or (11)C-methionine uptake in granulomatous lesions remains
      unclarified. In this study, the potentials of (18)F-FLT and (11)C-methionine in
      differentiating malignant tumors from granulomas were compared with (18)F-FDG
      using experimental rat models. METHODS: Dual-tracer tissue distribution studies
      using (18)F-FDG and (3)H-FLT (groups I and III) or (18)F-FDG and (14)C-methionine
      (groups II and IV) were performed on rats bearing both granulomas (Mycobacterium
      bovis bacillus Calmette-Guerin [BCG]-induced) and hepatomas (KDH-8-induced)
      (groups I and II) or on rats bearing both turpentine oil-induced inflammation and
      hepatomas (groups III and IV). One hour after the injection of a mixture of (18)F
      FDG and (3)H-FLT or of (18)F-FDG and (14)C-methionine, tissues were excised to
      determine the radioactivities of (18)F-FDG, (3)H-FLT, and (14)C-methionine
      (differential uptake ratio). RESULTS: Mature epithelioid cell granuloma formation
      and massive lymphocyte infiltration were observed in the granuloma tissue induced
      by BCG, histologically similar to sarcoidosis. The granulomas showed high (18)F
      FDG uptake comparable to that in the hepatomas (group I, 8.18 +/- 2.40 vs. 9.13
      +/- 1.52, P = NS; group II, 8.43 +/- 1.45 vs. 8.91 +/- 2.32, P = NS). (14)C
      Methionine uptake in the granuloma was significantly lower than that in the
      hepatoma (1.31 +/- 0.22 vs. 2.47 +/- 0.60, P < 0.01), whereas (3)H-FLT uptake in
      the granuloma was comparable to that in the hepatoma (1.98 +/- 0.70 vs. 2.30 +/-
      0.67, P = NS). Mean uptake of (18)F-FDG, (3)H-FLT, and (14)C-methionine was
      markedly lower in the turpentine oil-induced inflammation than in the tumor.
      CONCLUSION: (14)C-Methionine uptake was significantly lower in the granuloma than
      in the tumor, whereas (18)F-FDG and (3)H-FLT were not able to differentiate
      granulomas from tumors. These results suggest that (14)C-methionine has the
      potential to accurately differentiate malignant tumors from benign lesions,
      particularly granulomatous lesions, providing a biologic basis for clinical PET
      studies.

PMID- 18077526
TI  - A feasibility study of a prototype PET insert device to convert a general-purpose
      animal PET scanner to higher resolution.
AB  - We developed a prototype system to evaluate the feasibility of using a PET insert
      device to achieve higher resolution from a general-purpose animal PET scanner.
      METHODS: The system consists of a high-resolution PET detector, a computer
      controlled rotation stage, and a custom mounting plate. The detector consists of
      a cerium-doped lutetium oxyorthosilicate array (12 x 12 crystals, 0.8 x 1.66 x
      3.75 mm(3) each) directly coupled to a position-sensitive photomultiplier tube
      (PS-PMT). The detector signals were fed into the scanner electronics to establish
      coincidences between the 2 systems. The detector was mounted to a rotation stage
      that is attached to the scanner via the custom mounting plate after removing the
      transmission source holder. The rotation stage was concentric with the center of
      the scanner. The angular offset of the insert detector was calibrated via
      optimizing point-source images. In all imaging experiments, coincidence data were
      collected from 9 angles to provide 180 degrees sampling. A (22)Na point source
      was imaged at different offsets from the center to characterize the in-plane
      resolution of the insert system. A (68)Ge point source was stepped across the
      axial field of view to measure the sensitivity of the system. A 23.2-g mouse was
      injected with 38.5 MBq of (18)F-fluoride and imaged at 3 h after injection for 2
      h. RESULTS: The transverse image resolution of the PET insert device ranges from
      1.1- to 1.4-mm full width at half maximum (FWHM) without correction for the point
      source dimension. This corresponds to approximately 33% improvement over the
      resolution of the original scanner (1.7- to 1.8-mm FWHM) in 2 of the 3
      directions. The sensitivity of the device is 0.064% at the center of the field,
      46-fold lower than the sensitivity of an existing animal PET scanner. The mouse
      bone scan had improved image resolution using the PET insert device over that of
      the existing animal PET scanner alone. CONCLUSION: We have demonstrated the
      feasibility of using a high-resolution insert device in an existing PET scanner
      to provide high-resolution PET. A PET insert device with more detector modules
      will improve sensitivity and may become an alternative to special-purpose PET
      systems for high-resolution PET.

PMID- 18077527
TI  - 18F-FDG PET for posttherapy assessment of Hodgkin's disease and aggressive Non
      Hodgkin's lymphoma: a systematic review.
AB  - Although studies have shown that (18)F-FDG PET, when used to assess the response
      of malignant lymphoma after treatment, has a strong ability to predict relapse,
      its diagnostic accuracy in clinical practice remains unclear. The aim of this
      study was to systematically review the diagnostic accuracy of (18)F-FDG PET in
      detecting residual disease at the completion of first-line therapy of Hodgkin's
      disease (HD) and aggressive non-Hodgkin's lymphoma (NHL). METHODS: We searched
      relevant articles from 1966 to July 2006 using MEDLINE, EMBASE, SCOPUS,
      Biological Abstracts, bibliographies, review articles, and textbooks without
      language restriction. One assessor (for non-English-language studies) or 2
      assessors (for English-language studies) independently reviewed each article to
      abstract relevant study characteristics and results. Relevant individual patient
      data or subgroup data were provided by the investigators if they were unavailable
      from the publications. We estimated summary receiver operating characteristic
      curves and confidence regions for summary sensitivity and specificity. RESULTS:
      Nineteen studies consisting of 474 HD and 254 aggressive NHL patients were
      included. These studies had heterogeneity and suboptimal methodologic quality and
      reporting. Reported ranges for the sensitivity and specificity of (18)F-FDG PET
      in predicting disease relapse were 0.50-1.00 and 0.67-1.00, respectively, for HD
      and 0.33-0.77 and 0.82-1.00, respectively, for NHL. These estimates were similar
      when conventional imaging tests showed a residual mass. For HD studies, the
      summary receiver operating characteristic curves were similar irrespective of
      whether a residual mass was detected by conventional tests. Factors explaining
      the variability of diagnostic estimates were not identified. CONCLUSION: Although
      currently available evidence is still limited, (18)F-FDG PET seems to have good
      diagnostic accuracy for assessing residual HD at the completion of first-line
      treatment. Clinical data on this use of (18)F-FDG PET for aggressive NHL are more
      limited. Prospective studies with a more rigorous research design, conduct, and
      reporting would more reliably reveal the clinical diagnostic accuracy of this
      imaging modality.

PMID- 18077528
TI  - Optical imaging: current applications and future directions.
AB  - Optical techniques, such as bioluminescence and fluorescence, are emerging as
      powerful new modalities for molecular imaging in disease and therapy. Combining
      innovative molecular biology and chemistry, researchers have developed optical
      methods for imaging a variety of cellular and molecular processes in vivo,
      including protein interactions, protein degradation, and protease activity.
      Whereas optical imaging has been used primarily for research in small-animal
      models, there are several areas in which optical molecular imaging will translate
      to clinical medicine. In this review, we summarize recent advances in optical
      techniques for molecular imaging and the potential impact for clinical medicine.

PMID- 18077529
TI  - Skeletal PET with 18F-fluoride: applying new technology to an old tracer.
AB  - Although (18)F-labeled NaF was the first widely used agent for skeletal
      scintigraphy, it quickly fell into disuse after the introduction of (99m)Tc
      labeled bone-imaging agents. Recent comparative studies have demonstrated that
      (18)F-fluoride PET is more accurate than (99m)Tc-diphosphonate SPECT for
      identifying both malignant and benign lesions of the skeleton. Combining (18)F
      fluoride PET with other imaging, such as CT, can improve the specificity and
      overall accuracy of skeletal (18)F-fluoride PET and probably will become the
      routine clinical practice for (18)F-fluoride PET. Although (18)F-labeled NaF and
      (99m)Tc-diphosphonate have a similar patient dosimetry, (18)F-fluoride PET offers
      shorter study times (typically less than 1 h), resulting in a more efficient
      workflow, improved patient convenience, and faster turnarounds of reports to the
      referring physicians. With the widespread availability of PET scanners and the
      improved logistics for the delivery of (18)F radiopharmaceuticals, prior
      limitations to the routine use of (18)F-fluoride bone imaging have largely been
      overcome. The favorable imaging performance and the clinical utility of (18)F
      fluoride PET, compared with (99m)Tc-diphosphonate scintigraphy, support the
      reconsideration of (18)F-fluoride as a routine bone-imaging agent.

PMID- 18077530
TI  - Multifunctional antibodies by the Dock-and-Lock method for improved cancer
      imaging and therapy by pretargeting.
AB  - The Dock-and-Lock (DNL) method, which makes bioactive molecules with multivalency
      and multifunctionality, is a new approach to develop targeting molecules for
      improved cancer imaging and therapy. It involves the use of a pair of distinct
      protein domains involved in the natural association between cyclic adenosine
      monophosphate (cAMP)-dependent protein kinase A (PKA) and A-kinase anchoring
      proteins (AKAPs). The dimerization and docking domain found in the regulatory
      subunit of PKA and the anchoring domain (AD) of an interactive AKAP are each
      attached to a biologic entity, and the resulting derivatives, when combined,
      readily form a stably tethered complex of a defined composition that fully
      retains the functions of the individual constituents. The DNL method has
      generated several trivalent, bispecific, binding proteins, each consisting of 2
      identical Fab fragments linked site-specifically to a different Fab fragment. For
      example, 2 identical Fabs reacting with carcinoembryonic antigen (CEA) are bound
      to a Fab reacting with a hapten peptide that bears a diagnostic or therapeutic
      radionuclide. Using a 2-step, pretargeting method that separates the bivalent
      anti-CEA antibody targeting of tumor from the delivery of the radioactive peptide
      that is captured by the second Fab of the tri-Fab construct, an improved method
      of cancer imaging and therapy has been developed and shows very sensitive and
      specific targeting of CEA-expressing tumors for either diagnostic imaging, such
      as with immunoSPECT and immunoPET, or radioimmunotherapy. Improved therapeutic
      efficacy is shown with pretargeting in a pancreatic cancer xenograft model given
      a tri-Fab to a pancreatic cancer MUC1 and the hapten peptide labeled with (90)Y.

PMID- 18077531
TI  - Preclinical efficacy of the c-Met inhibitor CE-355621 in a U87 MG mouse xenograft
      model evaluated by 18F-FDG small-animal PET.
AB  - The purpose of this study was to evaluate the efficacy of CE-355621, a novel
      antibody against c-Met, in a subcutaneous U87 MG xenograft mouse model using
      (18)F-FDG small-animal PET. METHODS: CE-355621 or control vehicle was
      administered intraperitoneally into nude mice (drug-treated group, n = 12;
      control group, n = 14) with U87 MG subcutaneous tumor xenografts. Drug efficacy
      was evaluated over 2 wk using (18)F-FDG small-animal PET and compared with tumor
      volume growth curves. RESULTS: The maximum %ID/g (percentage injected dose per
      gram of tissue) of (18)F-FDG accumulation in mice treated with CE-355621 remained
      essentially unchanged over 2 wk, whereas the %ID/g of the control tumors
      increased 66% compared with the baseline. Significant inhibition of (18)F-FDG
      accumulation was seen 3 d after drug treatment, which was earlier than the
      inhibition of tumor volume growth seen at 7 d after drug treatment. CONCLUSION:
      CE-355621 is an efficacious novel antineoplastic chemotherapeutic agent that
      inhibits (18)F-FDG accumulation earlier than tumor volume changes in a mouse
      xenograft model. These results support the use of (18)F-FDG PET to assess early
      tumor response for CE-355621.

PMID- 18077532
TI  - Quantification of cerebral blood flow and oxygen metabolism with 3-dimensional
      PET and 15O: validation by comparison with 2-dimensional PET.
AB  - Quantitative PET with (15)O provides absolute values for cerebral blood flow
      (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)),
      and oxygen extraction fraction (OEF), which are used for assessment of brain
      pathophysiology. Absolute quantification relies on physically accurate
      measurement, which, thus far, has been achieved by 2-dimensional PET (2D PET),
      the current gold standard for measurement of CBF and oxygen metabolism. We
      investigated whether quantitative (15)O study with 3-dimensional PET (3D PET)
      shows the same degree of accuracy as 2D PET. METHODS: 2D PET and 3D PET
      measurements were obtained on the same day on 8 healthy men (age, 21-24 y). 2D
      PET was performed using a PET scanner with bismuth germanate (BGO) detectors and
      a 150-mm axial field of view (FOV). For 3D PET, a 3D-only tomograph with
      gadolinium oxyorthosilicate (GSO) detectors and a 156-mm axial FOV was used. A
      hybrid scatter-correction method based on acquisition in the dual-energy window
      (hybrid dual-energy window [HDE] method) was applied in the 3D PET study. Each
      PET study included 3 sequential PET scans for C(15)O, (15)O(2), and H(2)(15)O (3
      step method). The inhaled (or injected) dose for 3D PET was approximately one
      fourth of that for 2D PET. RESULTS: In the 2D PET study, average gray matter
      values (mean +/- SD) of CBF, CBV, CMRO(2), and OEF were 53 +/- 12 (mL/100
      mL/min), 3.6 +/- 0.3 (mL/100 mL), 3.5 +/- 0.5 (mL/100 mL/min), and 0.35 +/- 0.06,
      respectively. In the 3D PET study, scatter correction strongly affected the
      results. Without scatter correction, average values were 44 +/- 6 (mL/100
      mL/min), 5.2 +/- 0.6 (mL/100 mL), 3.3 +/- 0.4 (mL/100 mL/min), and 0.39 +/- 0.05,
      respectively. With the exception of OEF, values differed between 2D PET and 3D
      PET. However, average gray matter values of scatter-corrected 3D PET were
      comparable to those of 2D PET: 55 +/- 11 (mL/100 mL/min), 3.7 +/- 0.5 (mL/100
      mL), 3.8 +/- 0.7 (mL/100 mL/min), and 0.36 +/- 0.06, respectively. Even though
      the 2 PET scanners with different crystal materials, data acquisition systems,
      spatial resolution, and attenuation-correction methods were used, the agreement
      of the results between 2D PET and scatter-corrected 3D PET was excellent.
      CONCLUSION: Scatter coincidence is a problem in 3D PET for quantitative (15)O
      study. The combination of both the present PET/CT device and the HDE scatter
      correction permits quantitative 3D PET with the same degree of accuracy as 2D PET
      and with a lower radiation dose. The present scanner is also applicable to
      conventional steady-state (15)O gas inhalation if inhaled doses are adjusted
      appropriately.

PMID- 18077533
TI  - Clinical experience with alpha-particle emitting 211At: treatment of recurrent
      brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody
      81C6.
AB  - alpha-Particle-emitting radionuclides, such as (211)At, with a 7.2-h half-life,
      may be optimally suited for the molecularly targeted radiotherapy of
      strategically sensitive tumor sites, such as those in the central nervous system.
      Because of the much shorter range and more potent cytotoxicity of alpha-particles
      than of beta-particles, (211)At-labeled agents may be ideal for the eradication
      of tumor cells remaining after surgical debulking of malignant brain tumors. The
      main goal of this study was to investigate the feasibility and safety of this
      approach in patients with recurrent malignant brain tumors. METHODS: Chimeric
      antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71-347
      MBq of (211)At by use of N-succinimidyl 3-[(211)At]astatobenzoate. Eighteen
      patients were treated with (211)At-labeled ch81C6 ((211)At-ch81C6) administered
      into a surgically created resection cavity (SCRC) and then with salvage
      chemotherapy. Serial gamma-camera imaging and blood sampling over 24 h were
      performed. RESULTS: A total of 96.7% +/- 3.6% (mean +/- SD) of (211)At decays
      occurred in the SCRC, and the mean blood-pool percentage injected dose was < or =
      0.3. No patient experienced dose-limiting toxicity, and the maximum tolerated
      dose was not identified. Six patients experienced grade 2 neurotoxicity within 6
      wk of (211)At-ch81C6 administration; this neurotoxicity resolved fully in all but
      1 patient. No toxicities of grade 3 or higher were attributable to the treatment.
      No patient required repeat surgery for radionecrosis. The median survival times
      for all patients, those with glioblastoma multiforme, and those with anaplastic
      astrocytoma or oligodendroglioma were 54, 52, and 116 wk, respectively.
      CONCLUSION: This study provides proof of concept for regional targeted
      radiotherapy with (211)At-labeled molecules in oncology. Specifically, the
      regional administration of (211)At-ch81C6 is feasible, safe, and associated with
      a promising antitumor benefit in patients with malignant central nervous system
      tumors.

PMID- 18077534
TI  - Imaging of gene expression in live pancreatic islet cell lines using dual-isotope
      SPECT.
AB  - We are combining nuclear medicine with molecular biology to establish a
      sensitive, quantitative, and tomographic method with which to detect gene
      expression in pancreatic islet cells in vivo. Dual-isotope SPECT can be used to
      image multiple molecular events simultaneously, and coregistration of SPECT and
      CT images enables visualization of reporter gene expression in the correct
      anatomic context. We have engineered pancreatic islet cell lines for imaging with
      SPECT/CT after transplantation under the kidney capsule. METHODS: INS-1 832/13
      and alphaTC1-6 cells were stably transfected with a herpes simplex virus type 1
      thymidine kinase-green fluorescent protein (HSV1-thymidine kinase-GFP) fusion
      construct (tkgfp). After clonal selection, radiolabel uptake was determined by
      incubation with 5-(131)I-iodo-1-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)uracil
      ((131)I-FIAU) (alphaTC1-6 cells) or (123)I-FIAU (INS-1 832/13 cells). For the
      first set of in vivo experiments, SPECT was conducted after alphaTC1-6/tkgfp
      cells had been labeled with either (131)I-FIAU or (111)In-tropolone and
      transplanted under the left kidney capsule of CD1 mice. Reconstructed SPECT
      images were coregistered to CT. In a second study using simultaneous acquisition
      dual-isotope SPECT, INS-1 832/13 clone 9 cells were labeled with (111)In
      tropolone before transplantation. Mice were then systemically administered (123)I
      FIAU and data for both (131)I and (111)In were acquired simultaneously. RESULTS:
      alphaTC1-6/tkgfp cells showed a 15-fold greater uptake of (131)I-FIAU, and INS
      1/tkgfp cells showed a 12-fold greater uptake of (123)I-FIAU, compared with that
      of wild-type cells. After transplantation under the kidney capsule, both reporter
      gene expression and location of cells could be visualized in vivo with dual
      isotope SPECT. Immunohistochemistry confirmed the presence of glucagon- and
      insulin-positive cells at the site of transplantation. CONCLUSION: Dual-isotope
      SPECT is a promising method to detect gene expression in and location of
      transplanted pancreatic cells in vivo.

PMID- 18077535
TI  - SPECT low-field MRI system for small-animal imaging.
AB  - Localization of regions with increased uptake of radiotracer in small-animal
      SPECT is greatly facilitated when using coregistration with anatomic images of
      the same animal. As MRI has several advantages compared with CT (soft-tissue
      contrast and lack of ionizing radiation) we developed a SPECT/low-field MRI
      hybrid device for small-animal imaging. METHODS: A small-animal single-pinhole
      gamma-camera (pinhole, 1.5 mm in diameter and 12 cm in focal length) adjacent to
      a dedicated low-field (0.1 T) small MR imager (imaging volume, 10 x 10 x 6 cm(3))
      was used. The animal was placed in a warmed nonmagnetic polymethyl methacrylate
      imaging cell for MR acquisition, which was followed immediately by SPECT after
      translation of the imaging cell from one modality to the other. 3-Dimensional T1
      weighted sequences were used for MRI. Phantom studies enabled verification of a
      low attenuation (10%) for (99m)Tc and (201)Tl and a very slight increase in
      Compton scattering due to the radiofrequency coil and polymethyl methacrylate
      imaging cell. RESULTS: SPECT/MRI data acquisition and image coregistration of
      selected examples using different radiotracers for lungs, kidneys, and brain were
      obtained in 3 nude mice with isotropic spatial resolutions of 0.5 x 0.5 x 0.5
      mm(3) for MRI and 1 x 1 x 1 mm(3) for SPECT. The total acquisition time for
      combined SPECT and MRI lasted 1 h 45 min. CONCLUSION: A low-magnetic-field
      strength of 0.1 T is a simple and useful solution for a small-animal dual-imaging
      device combining pinhole SPECT with the adjacent MR imager.

PMID- 18077536
TI  - PET imaging of VPAC1 expression in experimental and spontaneous prostate cancer.
AB  - Among U.S. men, prostate cancer (PC) accounts for 29% of all newly diagnosed
      cancers. A reliable scintigraphic agent to image PC and its metastatic or
      recurrent lesions and to determine the effectiveness of its treatment will
      contribute to the management of this disease. All PC overexpresses VPAC1
      receptors. This investigation evaluated a probe specific for a (64)Cu-labeled
      receptor for PET imaging of experimental human PC in athymic nude mice and
      spontaneously grown PC in transgenic mice. METHODS: The probe, TP3939, was
      synthesized, purified, and labeled with (64)Cu and (99m)Tc. Using a muscle
      relaxivity assay, biologic activity was assessed and inhibitory concentrations of
      50% calculated. Receptor affinity (Kd) for human PC3 cells was determined using
      (99m)Tc-TP3939 and (64)CuCl(2.) Blood clearance and in vivo stability were
      studied. After intravenous administration of either (64)Cu-TP3939 or (64)CuCl(2)
      in PC3 xenografts and in transgenic mice, PET/CT images were acquired. Prostate
      histology served as the gold standard. Organ distribution studies (percentage
      injected dose per gram [%ID/g]) in normal prostate were performed. The ratios of
      tumor to muscle, tumor to blood, normal prostate to muscle, and tumor to normal
      prostate were determined. RESULTS: Chemical and radiochemical purities of TP3939
      were 96.8% and 98% +/- 2%, respectively. Inhibitory concentrations of 50% and
      affinity constants were 4.4 x 10(-8) M and 0.77 x 10(-9) M, respectively, for
      TP3939 and 9.1 x 10(-8) M and 15 x 10(-9) M, respectively, for vasoactive
      intestinal peptide 28. Binding of (64)CuCl(2) to PC3 was nonspecific. Blood
      clearance was rapid. In vivo transchelation of (64)Cu-TP3939 to plasma proteins
      was less than 15%. (64)Cu-TP3939 uptake in PC was 7.48 +/- 3.63 %ID/g at 4 h and
      5.78 +/- 0.66 %ID/g at 24 h after injection and was significantly (P < 0.05)
      greater than with (64)CuCl(2) (4.79 +/- 0.34 %ID/g and 4.03 +/- 0.83 %ID/g at 4
      and 24 h, respectively). The ratios of PC to normal prostate at 4 and 24 h were 4
      and 2.7, respectively. (64)Cu-TP3939 distinctly imaged histologic grade IV
      prostate intraepithelial neoplasia in transgenic mice, but (18)F-FDG and CT did
      not. CONCLUSION: Data indicate that TP3939, with its uncompromised biologic
      activity, delineated xenografts and cases of occult PC that were not detectable
      with (18)F-FDG. (64)Cu-TP3939 is a promising probe for PET imaging of PC. It may
      also be useful for localizing recurrent lesions and for determining the
      effectiveness of its treatment.

PMID- 18077537
TI  - 99mTc-GSA scintigraphy with SPECT for assessment of hepatic function and
      functional volume during liver regeneration in a rat model of partial
      hepatectomy.
AB  - Small-animal models are crucial to gain insights in the complex recovery
      mechanisms of liver function during liver regeneration. (99m)Tc-Mebrofenin
      hepatobiliary scintigraphy (HBS) has been introduced for noninvasive assessment
      of liver function in the clinical setting as well as in experimental research.
      However, HBS is restricted to planar modalities in small animals because hepatic
      kinetics are generally too fast for SPECT acquisition. (99m)Tc-DTPA-galactosyl
      serum albumin (where DTPA is diethylenetriaminepentaacetic acid) ((99m)Tc-GSA)
      scintigraphy is an alternative, receptor-mediated, noninvasive liver function
      test. After hepatic uptake, (99m)Tc-GSA remains trapped in the liver, which
      readily enables additional SPECT for the assessment of both liver function and
      liver functional volume within one test. In this study we evaluated the use of
      (99m)Tc-GSA scintigraphy combined with SPECT for the assessment of liver function
      and liver functional volume in normal and regenerating rat livers. METHODS: The
      reproducibility of (99m)Tc-GSA scintigraphy and SPECT was investigated by
      repeated measurements within the same rat. For the assessment in a regenerating
      liver, (99m)Tc-GSA scintigraphy with SPECT was performed on 1, 3, 5, and 7 d (n =
      6 rats per time point) after 70% partial hepatectomy (PH). RESULTS: The
      correlation between repeated (99m)Tc-GSA measurements was strong (r = 0.75, P =
      0.019). In normal rat livers, there was a strong, significant correlation between
      liver functional volume and conventional liver volume (r = 0.93; < 0.0001). The
      correlation between (99m)Tc-GSA uptake and liver volume was moderate (r = 0.62, P
      = 0.043). During the regeneration process, (99m)Tc-GSA uptake was significantly
      lower compared with both liver volume (P < 0.001) and liver functional volume (P
      < 0.001), when expressed as a percentage of baseline levels. There was a strong
      correlation between liver functional volume and conventional liver volume in the
      regenerating liver (r = 0.92, P < 0.0001). CONCLUSION: (99m)Tc-GSA scintigraphy
      combined with SPECT is a feasible, noninvasive method to assess hepatic
      functional volume in normal rat liver as well as in the regenerating rat liver.
      However, the hepatic (99m)Tc-GSA uptake as a liver function test seems to
      underestimate hepatic regeneration in comparison to liver volume.

PMID- 18077538
TI  - Comparison of integrin alphaVbeta3 expression and glucose metabolism in primary
      and metastatic lesions in cancer patients: a PET study using 18F-galacto-RGD and
      18F-FDG.
AB  - The expression of alpha(v)beta(3) and glucose metabolism are upregulated in many
      malignant lesions, and both are known to correlate with an aggressive phenotype.
      We evaluated whether assessment of alpha(v)beta(3) expression and of glucose
      metabolism with PET using (18)F-galacto-RGD and (18)F-FDG provides complementary
      information in cancer patients. METHODS: Eighteen patients with primary or
      metastatic cancer (non-small cell lung cancer [NSCLC], n = 10; renal cell
      carcinoma, n = 2; rectal cancer, n = 2; others, n = 4) were examined with PET
      using (18)F-galacto-RGD and (18)F-FDG. Standardized uptake values (SUVs) were
      derived by volume-of-interest analysis. (18)F-Galacto-RGD and (18)F-FDG PET
      results were compared using linear regression analysis for all lesions (n = 59;
      NSCLC, n = 39) and for primaries (n = 14) and metastases to bone (n = 11), liver
      (n = 10), and other organs (n = 24) separately. RESULTS: The sensitivity of (18)F
      galacto-RGD PET compared with clinical staging was 76%. SUVs for (18)F-FDG ranged
      from 1.3 to 23.2 (mean +/- SD, 7.6 +/- 4.9) and were significantly higher than
      SUVs for (18)F-galacto-RGD (range, 0.3-6.8; mean +/- SD, 2.7 +/- 1.5; P < 0.001).
      There was no significant correlation between the SUVs for (18)F-FDG and (18)F
      galacto-RGD for all lesions (r = 0.157; P = 0.235) or for primaries, osseous or
      soft-tissue metastases separately (P > 0.05). For the subgroup of lesions in
      NSCLC, there was a weak correlation between (18)F-FDG and (18)F-galacto-RGD
      uptake (r = 0.353; P = 0.028). CONCLUSION: Tracer uptake of (18)F-galacto-RGD and
      (18)F-FDG does not correlate closely in malignant lesions. Whereas (18)F-FDG PET
      is more sensitive for tumor staging, (18)F-galacto-RGD PET warrants further
      evaluation for planning and response evaluation of targeted molecular therapies
      with antiangiogenic or alpha(v)beta(3)-targeted drugs.

PMID- 18077539
TI  - A bacterial metapopulation adapts locally to phage predation despite global
      dispersal.
AB  - Using a combination of bacterial and phage-targeted metagenomics, we analyzed two
      geographically remote sludge bioreactors enriched in a single bacterial species
      Candidatus Accumulibacter phosphatis (CAP). We inferred unrestricted global
      movement of this species and identified aquatic ecosystems as the primary
      environmental reservoirs facilitating dispersal. Highly related and
      geographically remote CAP strains differed principally in genomic regions
      encoding phage defense mechanisms. We found that CAP populations were high
      density, clonal, and nonrecombining, providing natural targets for "kill-the
      winner" phage predation. Community expression analysis demonstrated that phages
      were consistently active in the bioreactor community. Genomic signatures linking
      CAP to past phage exposures were observed mostly between local phage and host. We
      conclude that CAP strains disperse globally but must adapt to phage predation
      pressure locally.

PMID- 18077540
TI  - Screening for hip and knee osteoarthritis in the general population: predictive
      value of a questionnaire and prevalence estimates.
AB  - OBJECTIVE: To study the feasibility and validity of a two-step telephone
      screening procedure for symptomatic knee and hip osteoarthritis (OA) in the
      general population. METHOD: The screening questionnaire was based on signs and
      symptoms, previous diagnosis of OA and validated OA criteria. A random sample of
      telephone numbers was obtained and, at each number, one person aged 40-75 years
      was included. A physical examination and knee or hip radiographs were offered
      when the screen was positive. A sample of subjects with negative screens was also
      examined. The diagnosis of hip/knee OA was based on the American College of
      Rheumatology criteria for signs and symptoms and Kellgren-Lawrence radiographic
      stage 2 or greater. Prevalence rates were estimated with correction for the
      performance of the screening procedure. RESULTS: Of 1380 subjects, 479 had
      positive screens, among whom 109 were evaluated; symptomatic radiographic OA was
      found in 50 subjects, at the knee (n = 35) or hip (n = 20). Corrected prevalence
      estimates of symptomatic OA were 7.6% (6.4%-8.8%) for the knee and 5% (3.9%-6.1%)
      for the hip. The screening procedure had 87% (95% CI 79% to 95%) sensitivity and
      92% (95% CI 91% to 93%) specificity for detecting knee OA and respectively 93%
      (95% CI 86% to 100%) and 93% (95% CI 92% to 94%) for hip OA. CONCLUSION: This
      study establishes the feasibility of telephone screening for symptomatic knee/hip
      OA, which could be used for a nationwide prevalence study. Pain and previous OA
      diagnosis were the best items for detecting symptomatic OA.

PMID- 18077541
TI  - The biomechanical link between skin and joint disease in psoriasis and psoriatic
      arthritis: what every dermatologist needs to know.

PMID- 18077542
TI  - The history of osteoarthritis-osteoarthrosis.
AB  - The history of osteoarthritis-osteoarthrosis from antiquity to the present day is
      elaborated through historical accounts in the literature, paleopathological
      findings in skeletal remains, visual representations in artwork and new
      developments in pathophysiological concepts of the disease.

PMID- 18077543
TI  - Functional variants of the macrophage migration inhibitory factor do not infer
      risk of cardiovascular disease in rheumatoid arthritis.

PMID- 18077544
TI  - Consistency in assessing the Disease Activity Score-28 in routine clinical
      practice.

PMID- 18077545
TI  - High prevalence of autoantibodies to muscarinic-3 acetylcholine receptor in
      patients with juvenile-onset Sjogren syndrome.

PMID- 18077546
TI  - Association of the IFIH1-GCA-KCNH7 chromosomal region with rheumatoid arthritis.

PMID- 18077547
TI  - HLA-B27 and ankylosing spondylitis geographic distribution versus malaria
      endemic: casual or causal liaison?

PMID- 18077549
TI  - Glucuronylation in Escherichia coli for the bacterial synthesis of the
      carbohydrate moiety of nonsulfated HNK-1.
AB  - We have previously reported the large-scale synthesis of neolactotetraose
      (Galbeta-4GlcNAcbeta-3Galbeta-4Glc) from lactose in engineered Escherichia coli
      cells (Priem B, Gilbert M, Wakarchuk WW, Heyraud A and Samain E. 2002. A new
      fermentation process allows large-scale production of human milk oligosaccharides
      by metabolically engineered bacteria. Glycobiology. 12:235-240). In the present
      study we analyzed the adaptation of this system to glucuronylated
      oligosaccharides. The catalytic domain of mouse glucuronyl transferase GlcAT-P
      was cloned and expressed in an engineered strain which performed the in vivo
      synthesis of neolactotetraose. Under these conditions, efficient glucuronylation
      of neolactotetraose was achieved, but some residual neolactotetraose was still
      present. Although E. coli K-12 has an indigenous UDP-glucose dehydrogenase, the
      yield of glucuronylated oligosaccharides was greatly improved by the additional
      expression of the orthologous gene kfiD from E. coli K5. Glucuronylation of
      neolactohexaose and lactose was also observed. The final glucuronylated
      oligosaccharides are precursors of the brain carbohydrate motif HNK-1, involved
      in neural cell adhesion.

PMID- 18077550
TI  - CMP substitutions preferentially inhibit polysialic acid synthesis.
AB  - It is widely reported that derivatives of sugar moieties can be used to
      metabolically label cell surface carbohydrates or inhibit a particular
      glycosylation. However, few studies address the effect of substitution of the
      cytidylmonophosphate (CMP) portion on sialyltransferase activities. Here we first
      synthesized 2'-O-methyl CMP and 5-methyl CMP and then asked if these CMP
      derivatives are recognized by alpha2,3-sialyltransferases (ST3Gal-III and ST3Gal
      IV), alpha2,6-sialyltransferase (ST6Gal-I), and alpha2,8-sialyltransferase
      (ST8Sia-II, ST8Sia-III, and ST8Sia-IV). We found that ST3Gal-III and ST3Gal-IV
      but not ST6Gal-I was inhibited by 2'-O-methyl CMP as potently as by CMP, while
      ST3Gal-III, ST3Gal-IV, and ST6Gal-I were moderately inhibited by 5-methyl CMP.
      Previously, it was reported that polysialyltransferase ST8Sia-II but not ST8Sia
      IV was inhibited by CMP N-butylneuraminic acid. We found that ST8Sia-IV as well
      as ST8Sia-II and ST8Sia-III are inhibited by 2'-O-methyl CMP as robustly as by
      CMP and moderately by 5-methyl CMP. Moreover, the addition of CMP, 2'-O-methyl
      CMP, and 5-methyl CMP to the culture medium resulted in the decrease of
      polysialic acid expression on the cell surface and NCAM of Chinese hamster ovary
      cells. These results suggest that 2'-O-methyl CMP and 5-methyl CMP can be used to
      preferentially inhibit sialyltransferases, in particular, polysialyltransferases
      in vitro and in vivo. Such inhibition may be useful to determine the function of
      a carbohydrate synthesized by a specific sialyltransferase such as
      polysialyltransferase.

PMID- 18077551
TI  - Arx1 is a nuclear export receptor for the 60S ribosomal subunit in yeast.
AB  - We previously showed that nuclear export of the large (60S) ribosomal subunit
      relies on Nmd3 in a Crm1-dependent manner. Recently the general mRNA export
      factor, the Mtr2/Mex67 heterodimer, was shown to act as an export receptor in
      parallel with Crm1. These observations raise the possibility that nuclear export
      of the 60S subunit in Saccharomyces cerevisiae requires multiple export
      receptors. Here, we show that the previously characterized 60S subunit biogenesis
      factor, Arx1, also acts as an export receptor for the 60S subunit. We found that
      deletion of ARX1 was synthetic lethal with nmd3 and mtr2 mutants and was
      synthetic sick with several nucleoporin mutants. Deletion of ARX1 led to
      accumulation of pre-60S particles in the nucleus that were enriched for Nmd3,
      Crm1, Mex67, and Mtr2, suggesting that in the absence of Arx1, 60S export is
      impaired even though the subunit is loaded with export receptors. Finally, Arx1
      interacted with several nucleoporins in yeast two-hybrid as well as in vitro
      assays. These results show that Arx1 can directly bridge the interaction between
      the pre-60S particle and the NPC and thus is a third export receptor for the 60S
      subunit in yeast.

PMID- 18077552
TI  - Regulation of Tsg101 expression by the steadiness box: a role of Tsg101
      associated ligase.
AB  - As part of the endosomal sorting complex required for transport (ESCRT)
      machinery, Tsg101 is essential for endosomal sorting, membrane receptor
      degradation and the final stages of cytokinesis. Depletion or overproduction of
      the protein can cause disruption of these vital processes and results in severe
      consequences for the cell. Tsg101 expression is thus controlled
      posttranslationally within a narrow range and this autoregulation has been mapped
      to the C-terminus of the protein. Here we elucidate further the mechanisms of
      this regulation and describe a novel function of Tsg101-associated ligase (Tal)
      in mediating this control. We show that Tal polyubiquitinates lysine residues in
      the C-terminus of uncomplexed Tsg101, resulting in proteasomal degradation.
      However, accessibility to these lysines is prevented by the presence of the other
      ESCRT-I proteins. We show that VPS28 is a limiting factor, and consequently
      Tsg101 expression surplus to ESCRT-I function is vulnerable to degradation. The
      role of Tal in the regulation of Tsg101 steady-state control is highlighted when
      Tsg101 is overexpressed; however, our data also suggest that additional ligases
      regulate Tsg101 expression under normal conditions. Lastly, we demonstrate that
      while the C-terminal lysines are targets for polyubiquitination, they are not
      required for any additional function necessary for ESCRT activity.

PMID- 18077553
TI  - The Atg1 kinase complex is involved in the regulation of protein recruitment to
      initiate sequestering vesicle formation for nonspecific autophagy in
      Saccharomyces cerevisiae.
AB  - Autophagy is the major degradative process for recycling cytoplasmic constituents
      and eliminating unnecessary organelles in eukaryotic cells. Most autophagy
      related (Atg) proteins are recruited to the phagophore assembly site (PAS), a
      proposed site for vesicle formation during either nonspecific or specific types
      of autophagy. Therefore, appropriate recruitment of Atg proteins to this site is
      critical for their function in autophagy. Atg11 facilitates PAS recruitment for
      the cytoplasm-to-vacuole targeting pathway, which is a specific, autophagy-like
      process that occurs under vegetative conditions. In contrast, it is not known how
      Atg proteins are recruited to the PAS, nor which components are involved in PAS
      formation under nonspecific autophagy-inducing, starvation conditions. Here, we
      studied PAS assembly during nonspecific autophagy, using an atg11Delta mutant
      background to eliminate the PAS formation that occurs during vegetative growth.
      We found that protein complexes containing the Atg1 kinase have two roles for PAS
      formation during nonspecific autophagy. The Atg1 C terminus mediates an
      interaction with Atg13 and Atg17, facilitating a structural role of Atg1 that is
      needed to efficiently organize an initial step of PAS assembly, whereas Atg1
      kinase activity affects the dynamics of protein movement at the PAS involved in
      Atg protein cycling.

PMID- 18077554
TI  - The inositol 1,4,5-trisphosphate receptor is required to signal autophagic cell
      death.
AB  - The signaling pathways governing pathophysiologically important autophagic (ACD)
      and necrotic (NCD) cell death are not entirely known. In the Dictyostelium
      eukaryote model, which benefits from both unique analytical and genetic
      advantages and absence of potentially interfering apoptotic machinery, the
      differentiation factor DIF leads from starvation-induced autophagy to ACD, or, if
      atg1 is inactivated, to NCD. Here, through random insertional mutagenesis, we
      found that inactivation of the iplA gene, the only gene encoding an inositol
      1,4,5-trisphosphate receptor (IP3R) in this organism, prevented ACD. The IP3R is
      a ligand-gated channel governing Ca(2+) efflux from endoplasmic reticulum stores
      to the cytosol. Accordingly, Ca(2+)-related drugs also affected DIF signaling
      leading to ACD. Thus, in this system, a main pathway signaling ACD requires IP3R
      and further Ca(2+)-dependent steps. This is one of the first insights in the
      molecular understanding of a signaling pathway leading to autophagic cell death.

PMID- 18077555
TI  - Maintenance of hormone-sensitive phosphoinositide pools in the plasma membrane
      requires phosphatidylinositol 4-kinase IIIalpha.
AB  - Type III phosphatidylinositol (PtdIns) 4-kinases (PI4Ks) have been previously
      shown to support plasma membrane phosphoinositide synthesis during phospholipase
      C activation and Ca(2+) signaling. Here, we use biochemical and imaging tools to
      monitor phosphoinositide changes in the plasma membrane in combination with
      pharmacological and genetic approaches to determine which of the type III PI4Ks
      (alpha or beta) is responsible for supplying phosphoinositides during agonist
      induced Ca(2+) signaling. Using inhibitors that discriminate between the alpha-
      and beta-isoforms of type III PI4Ks, PI4KIIIalpha was found indispensable for the
      production of phosphatidylinositol 4-phosphate (PtdIns4P), phosphatidylinositol
      4,5-bisphosphate [PtdIns(4,5)P(2)], and Ca(2+) signaling in angiotensin II
      (AngII)-stimulated cells. Down-regulation of either the type II or type III PI4K
      enzymes by small interfering RNA (siRNA) had small but significant effects on
      basal PtdIns4P and PtdIns(4,5)P(2) levels in (32)P-labeled cells, but only
      PI4KIIIalpha down-regulation caused a slight impairment of PtdIns4P and
      PtdIns(4,5)P(2) resynthesis in AngII-stimulated cells. None of the PI4K siRNA
      treatments had a measurable effect on AngII-induced Ca(2+) signaling. These
      results indicate that a small fraction of the cellular PI4K activity is
      sufficient to maintain plasma membrane phosphoinositide pools, and they
      demonstrate the value of the pharmacological approach in revealing the pivotal
      role of PI4KIIIalpha enzyme in maintaining plasma membrane phosphoinositides.

PMID- 18077556
TI  - Divergent regulation of protein synthesis in the cytosol and endoplasmic
      reticulum compartments of mammalian cells.
AB  - In eukaryotic cells, mRNAs encoding signal sequence-bearing proteins undergo
      translation-dependent trafficking to the endoplasmic reticulum (ER), thereby
      restricting secretory and integral membrane protein synthesis to the ER
      compartment. However, recent studies demonstrating that mRNAs encoding
      cytosolic/nucleoplasmic proteins are represented on ER-bound polyribosomes
      suggest a global role for the ER in cellular protein synthesis. Here, we examined
      the steady-state protein synthesis rates and compartmental distribution of newly
      synthesized proteins in the cytosol and ER compartments. We report that ER
      protein synthesis rates exceed cytosolic protein synthesis rates by 2.5- to 4
      fold; yet, completed proteins accumulate to similar levels in the two
      compartments. These data suggest that a significant fraction of cytosolic
      proteins undergo synthesis on ER-bound ribosomes. The compartmental differences
      in steady-state protein synthesis rates correlated with a divergent regulation of
      the tRNA aminoacylation/deacylation cycle. In the cytosol, two pathways were
      observed to compete for aminoacyl-tRNAs-protein synthesis and aminoacyl-tRNA
      hydrolysis-whereas on the ER tRNA deacylation is tightly coupled to protein
      synthesis. These findings identify a role for the ER in global protein synthesis,
      and they suggest models where compartmentalization of the tRNA
      acylation/deacylation cycle contributes to the regulation of global protein
      synthesis rates.

PMID- 18077557
TI  - Munc18-1 is critical for plasma membrane localization of syntaxin1 but not of
      SNAP-25 in PC12 cells.
AB  - Although Munc18-1 was originally identified as a syntaxin1-interacting protein,
      the physiological significance of this interaction remains unclear. In fact,
      recent studies of Munc18-1 mutants have suggested that Munc18-1 plays a critical
      role for docking of secretory vesicles, independent of syntaxin1 regulation. Here
      we investigated the role of Munc18-1 in syntaxin1 localization by generating
      stable neuroendocrine cell lines in which Munc18-1 was strongly down-regulated.
      In these cells, the secretion capability, as well as the docking of dense-core
      vesicles, was significantly reduced. More importantly, not only was the
      expression level of syntaxin1 reduced, but the localization of syntaxin1 at the
      plasma membrane was also severely perturbed. The mislocalized syntaxin1 resided
      primarily in the perinuclear region of the cells, in which it was highly
      colocalized with Secretogranin II, a marker protein for dense-core vesicles. In
      contrast, the expression level and the plasma membrane localization of SNAP-25
      were not affected. Furthermore, the syntaxin1 localization and the secretion
      capability were restored upon transfection-mediated reintroduction of Munc18-1.
      Our results indicate that endogenous Munc18-1 plays a critical role for the
      plasma membrane localization of syntaxin1 in neuroendocrine cells and therefore
      necessitates the interpretation of Munc18-1 mutant phenotypes to be in terms of
      mislocalized syntaxin1.

PMID- 18077559
TI  - Biphasic incorporation of centromeric histone CENP-A in fission yeast.
AB  - CENP-A is a centromere-specific histone H3 variant that is essential for
      kinetochore formation. Here, we report that the fission yeast Schizosaccharomyces
      pombe has at least two distinct CENP-A deposition phases across the cell cycle: S
      and G2. The S phase deposition requires Ams2 GATA factor, which promotes histone
      gene activation. In Delta ams2, CENP-A fails to retain during S, but it
      reaccumulates onto centromeres via the G2 deposition pathway, which is down
      regulated by Hip1, a homologue of HIRA histone chaperon. Reducing the length of
      G2 in Delta ams2 results in failure of CENP-A accumulation, leading to chromosome
      missegregation. N-terminal green fluorescent protein-tagging reduces the
      centromeric association of CENP-A, causing cell death in Delta ams2 but not in
      wild-type cells, suggesting that the N-terminal tail of CENP-A may play a pivotal
      role in the formation of centromeric nucleosomes at G2. These observations imply
      that CENP-A is normally localized to centromeres in S phase in an Ams2-dependent
      manner and that the G2 pathway may salvage CENP-A assembly to promote genome
      stability. The flexibility of CENP-A incorporation during the cell cycle may
      account for the plasticity of kinetochore formation when the authentic centromere
      is damaged.

PMID- 18077558
TI  - Activation outcomes induced in naive CD8 T-cells by macrophages primed via
      "phagocytic" and nonphagocytic pathways.
AB  - The array of phagocytic receptors expressed by macrophages make them very
      efficient at pathogen clearance, and the phagocytic process links innate with
      adaptive immunity. Primary macrophages modulate antigen cross-presentation and T
      cell activation. We assessed ex vivo the putative role of different phagocytic
      receptors in immune synapse formation with CD8 naive T-cells from OT-I transgenic
      mice and compared this with the administration of antigen as a soluble peptide.
      Macrophages that have phagocytosed antigen induce T-cell microtubule-organizing
      center and F-actin cytoskeleton relocalization to the contact site, as well as
      the recruitment of proximal T-cell receptor signals such as activated Vav1 and
      PKC. At the same doses of loaded antigen (1 microM), "phagocytic" macrophages
      were more efficient than peptide-antigen-loaded macrophages at forming productive
      immune synapses with T-cells, as indicated by active T-cell TCR/CD3 conformation,
      LAT phosphorylation, IL-2 production, and T-cell proliferation. Similar T-cell
      proliferation efficiency was obtained when low doses of soluble peptide (3-30 nM)
      were loaded on macrophages. These results suggest that the pathway used for
      antigen uptake may modulate the antigen density presented on MHC-I, resulting in
      different signals induced in naive CD8 T-cells, leading either to CD8 T-cell
      activation or anergy.

PMID- 18077561
TI  - Chronic hypertension aggravates heat stress induced cognitive dysfunction and
      brain pathology: an experimental study in the rat, using growth hormone therapy
      for possible neuroprotection.
AB  - Hyperthermia following heat stress results in profound brain edema formation and
      damage to the central nervous system (CNS). However, whether acute or chronic
      diseases such as cardiovascular, endocrine, or metabolic ailments further
      influence the vulnerability of human populations to heat-related deaths is still
      unclear. In this investigation, we examined the effect of hyperthermia on chronic
      hypertensive rats. The influence of growth hormone (GH) as a therapy to attenuate
      brain dysfunction was also evaluated. Subjecting rats to 4 h of heat stress at 38
      degrees C in a biological oxygen demand (BOD) incubator resulted in profound
      impairment of motor and cognitive functions, breakdown of the blood-brain barrier
      (BBB), reduction in regional cerebral blood flow (CBF), edema formation, and
      brain damage. These effects were further aggravated when chronic hypertensive
      rats (two-kidney, one-clip model for 4 weeks) were subjected to similar
      hyperthermic conditions (38 degrees C for 4 h). Interestingly, the behavioral
      alterations and impairment of motor and cognitive functions in hypertensive rats
      were much worse than those in the normotensive animals subjected to heat stress.
      Pretreatment with GH (50 microg/kg/min i.v. for 60 min, before heat stress)
      significantly attenuated behavioral and cognitive deficits in normotensive rats
      and reduced the BBB dysfunction and brain pathology. On the other hand, similar
      treatment with GH in hypertensive animals only mildly reduced brain damage or
      cognitive dysfunction after heat stress. These novel observations indicate that
      patients suffering from various chronic diseases respond differently to various
      health hazards such as hyperthermia and to other neuroprotective agents.

PMID- 18077562
TI  - The brain as a target for inflammatory processes and neuroprotective strategies.
AB  - The importance of glial cell-propagated inflammation (i.e., neuroinflammation)
      disorders such as Alzheimer's disease (AD) was viewed previously as a bystander
      effect, or epiphenomenon, with inflammation occurring when damaged neurons elicit
      an activation response by glia. However, an accumulating body of evidence has
      challenged this earlier perspective and indicates a more active role of
      neuroinflammation in the pathophysiology of progressive neurodegenerative
      disorders such as AD, Parkinson's disease, amyotrophic lateral sclerosis, and
      multiple sclerosis. This insight into pathophysiology evolved in concert with the
      appreciation that the brain is not as immunologically privileged as once thought.
      The central nervous system (CNS) has its own resident immune system, in which
      glial cells (microglia, astrocytes, and oligodendrocytes) not only serve
      supportive and nutritive roles for neurons but also engage from time to time in
      several "inflammatory" processes that defend the CNS from pathogens and help it
      to recover from stress and injury. These otherwise "normal" glial functions can
      sometimes result in a more severe and chronic neuroinflammatory cycle that
      actually promotes or propagates neurodegenerative disease. Excessive glial cell
      activation may thus constitute a viable target for the discovery of and
      development of neurodegenerative disease therapeutics. Suggestive clinical
      evidence in support of neuroinflammation as a drug discovery target for chronic
      neurodegenerative diseases, such as AD, comes from epidemiological and genetic
      linkage data. For example, long-term use of nonsteroidal anti-inflammatory drugs
      is correlated with a protective effect against AD, and certain polymorphisms in
      the genes for interleukin 1 and other proinflammatory mediator genes are
      associated with increased risk. In AD and Parkinson's disease, activated
      microglia and complement proteins have been identified in the brain regions most
      affected in these disorders. This report will briefly review selected clinical
      and preclinical data that reflect the prevailing approaches targeting
      neuroinflammation as a pathophysiological process contributing to the onset or
      progression of neurodegenerative diseases, as well as their neuroprotective
      potential.

PMID- 18077563
TI  - Genetic and hormonal regulation of tryptophan kynurenine metabolism: implications
      for vascular cognitive impairment, major depressive disorder, and aging.
AB  - Impairment of cognition that is caused by (or associated with) vascular factors
      has been termed vascular cognitive impairment (VCI). The hallmark of VCI is an
      impairment of brain executive, or planning, functions caused by inflammatory
      changes of brain microvessels. VCI is characterized by impairment of the
      executive function and is distinct from Alzheimer's-type and multi-infarct
      dementias, although VCI might overlap with Alzheimer's disease. This review
      focuses on the possible contribution of the kynurenine pathway of tryptophan
      (Try) catabolism to the inflammatory changes in brain microvessels. One mechanism
      of brain microvessel inflammation is activation of the inducible nitric oxide
      synthase (iNOS) by the proinflammatory cytokine interferon gamma (IFN-gamma). The
      effect of IFN-gamma on iNOS might be mediated by kynurenine derivatives of
      tryptophan because (1) IFN-gamma stimulates the rate-determining enzyme of the
      Try-kynurenine pathway, indoleamine-2,3-dioxygenase (IDO) and (2) some
      kynurenines (e.g., quinolinic and picolinic acids) can stimulate iNOS. IFN-gamma
      production is controlled by (IFN-gamma) + 874(T/A) genotypes, suggesting the
      association of a high promoter T allele with the high rate of IFN-gamma
      production and, consequently, with activated IDO and enhanced production of
      kynurenines. Although IDO is strictly an IFN-gamma-induced gene product, tumor
      necrosis factor alpha (TNF-alpha) can synergistically increase the
      transcriptional activation of the IDO gene in response to IFN-gamma. The
      combination of high promoter T of (IFN-gamma) + 874(T/A) with high promoter A of
      (TNF-alpha) -308(G/A) might "superinduce" IDO and cause (or contribute to)
      inflammation of brain microvessels detected as white matter hyperintensities and
      leading to VCI development. Hormonal induction of tryptophan dioxygenase and the
      ability of hormones to potentiate IFN-gamma-induced activation of IDO might
      contribute to the development of inflammatory changes in major depressive
      disorder and in aging. The IFN-gamma-IDO-iNOS hypothesis of VCI suggests new ways
      of preventing (identifying population at risk by analysis of IFN-gamma and TNF
      alpha genetic polymorphism) and treating VCI (using IDO inhibitors and melatonin
      and bupropion [Wellbutrin] as agents suppressing IFN-gamma and TNF-alpha
      production).

PMID- 18077564
TI  - Metabolic syndrome in drug abuse.
AB  - Drug abuse is associated with significant health risk. Whether drug abusers are
      at a higher risk of suffering the metabolic syndrome is not widely known. The
      metabolic syndrome is a cluster of metabolic abnormalities, including
      hyperinsulinemia, hypertension, dyslipidemia, and abdominal obesity, and is
      probably triggered by initial imbalances at the cellular level in various
      critical metabolic pathways. These initially small metabolic imbalances are
      believed to cascade with time and lead to larger problems. Some indications that
      drug abuse may increase the risk of the metabolic syndrome include the following:
      Drug-abusing patients have higher rates of diabetes complications. Substance
      abuse is a significant contributing factor for treatment noncompliance in
      diabetes. Nutrition education can enhance substance abuse treatment outcomes.
      Each type of drug/substance abuse has a unique profile of toxicity. For example,
      the amphetamines generally affect the cardiovascular and neurological systems,
      worsening the risk factors for the metabolic syndrome. Methamphetamine (meth)
      abusers suffer cognitive deficits and abnormal metabolic activity, which affect
      nutritional status. This condition is further worsened by a drastic reduction in
      oral health in meth abusers, resulting in improper chewing and, therefore,
      digestion. Nutritional deficiency in combination with drug abuse would increase
      the risk of developing the metabolic syndrome by increasing cell damage,
      augmenting excitotoxicity, reducing energy production, and lowering the
      antioxidant potential of the cells. Another potential risk factor in the
      development of the metabolic syndrome is genetic vulnerability, especially in
      combination with drug abuse and nutritional deficiencies. The strategies
      available to treat this problem include pharmacological agents as well as dietary
      antioxidants. Such measures may be useful in reducing drug abuse-related toxicity
      that may lead to the metabolic syndrome.

PMID- 18077565
TI  - Early exposure to general anesthesia causes significant neuronal deletion in the
      developing rat brain.
AB  - Frequent exposure of children to general anesthesia is common practice in modern
      medicine. Although previously unrecognized, recent in vitro and in vivo animal
      studies suggest that exposure to clinically relevant general anesthetics at the
      peak of brain development could be detrimental to immature mammalian neurons, as
      demonstrated by massive and widespread apoptotic neurodegeneration. The survival
      of the developing neurons presumably depends on proper and timely formation of
      synapses, for which synaptic proteins (e.g., synaptophysin, synaptobrevin,
      amphiphysin, synaptosomal-associated protein 25 [SNAP-25], and Ca(2+)/calmodulin
      dependent protein kinase II [CaM kinase II]) are crucially important.
      Overinhibition of developing neurons impairs synaptic protein function and
      activity-induced synaptic plasticity, which could in turn result in permanent
      neuronal loss. To examine the effects of general anesthesia, the pharmacological
      agents known to cause extensive neuronal inhibition, on synaptic proteins, and
      neuronal survival at the peak of synaptogenesis, we exposed 7-day-old rat pups to
      general anesthesia (midazolam, 9 mg/kg of body weight, subcutaneously, followed
      by 6 h of nitrous oxide 75 vol% and isoflurane 0.75 vol%). We found that this
      general anesthesia causes permanent neuronal deletion in the most vulnerable
      brain regions-the cerebral cortex and the thalamus-while transiently modulating
      protein levels of synaptophysin, synaptobrevin, amphiphysin, SNAP-25, and CaM
      kinase II.

PMID- 18077566
TI  - Inhibition of T-type calcium current in the reticular thalamic nucleus by a novel
      neuroactive steroid.
AB  - Neurons of the nucleus reticularis of the thalamus (nRT) serve as an important
      inhibitory gate that controls trafficking of thalamocortical sensory signals and
      states of sleep, arousal, and epilepsy. T-type calcium channels in nRT play a
      crucial role in the subthreshold excitability of these neurons, but their
      modulation by neuroactive steroids has not been previously studied. Here we
      explored the effect of (3beta,5beta,17beta)-3-hydroxyandrostane-17-carbonitrile
      (3beta-OH), a novel neuroactive steroid on T-type currents recorded from nRT
      neurons in intact brain slices of young rats. We found in voltage-clamp
      experiments that 3beta-OH potently and reversibly decreased T-type Ca(2+) current
      amplitude and stabilized inactive states of the channels. In current-clamp
      experiments, 3beta-OH significantly decreased the frequency of action potential
      firing from negative membrane potentials and minimally changed passive membrane
      properties. Our results indicate that 5beta-reduced neuroactive steroids, through
      the mechanisms of inhibition of T-type Ca(2+) currents and diminished spike
      firing in nRT neurons, may be important agents in control of sensory information
      processing in physiological conditions and possibly pathological brain states
      associated with increased cellular excitability such as epilepsy and/or tissue
      ischemia/hypoxia.

PMID- 18077567
TI  - A select combination of neurotrophins enhances neuroprotection and functional
      recovery following spinal cord injury.
AB  - Previously, we have shown that topical application of brain-derived neurotrophic
      factor (BDNF) or insulin-like growth factor 1 (IGF-1) given within 5 to 30 min
      after a focal trauma to the rat spinal cord attenuates spinal cord injury (SCI)
      induced breakdown of the blood-spinal cord barrier (BSCB), edema formation, motor
      dysfunction, and cell injury. This investigation was undertaken to find out
      whether a combination of select neurotrophins (BDNF, glial cell line-derived
      neurotrophic factor [GDNF], neurotrophin 3 [NT-3], or nerve growth factor [NGF])
      will further enhance the neuroprotective efficacy of growth factors in SCI. The
      neurotrophins (0.1-1 microg/10 microL in phosphate-buffered saline) were applied
      30, 60, or 90 min after injury topically over the traumatized spinal cord either
      alone or in combination. The SCI was performed by making a unilateral incision
      into the right dorsal horn of the T10-T11 segment under Equithesin anesthesia.
      The rats were allowed to survive 5 h after trauma. Topical application of BDNF,
      GDNF, or NGF 30 min after SCI in high concentration (0.5 microg and 1 microg)
      significantly improved the motor functions and reduced the BSCB breakdown, edema
      formation, and cell injury seen at 5 h. These beneficial effects of neurotropins
      were absent when administered separately either 60 or 90 min after SCI. However,
      a combination of BDNF and GDNF (but not with NT-3 or NGF) given either 60 or 90
      min after SCI significantly reduced the motor dysfunction and spinal cord
      pathology at 5 h. These novel observations suggest that a select group of
      neurotrophins in combination have potential therapeutic value for the treatment
      of SCI in clinical situations.

PMID- 18077568
TI  - Intracerebroventricularly administered neurotrophins attenuate blood
      cerebrospinal fluid barrier breakdown and brain pathology following whole-body
      hyperthermia: an experimental study in the rat using biochemical and
      morphological approaches.
AB  - Previous studies from our laboratory show that apart from blood-brain barrier
      (BBB) disruption, the blood-cerebrospinal fluid (CSF) barrier (BCSFB) for
      proteins is also broken down following whole-body hyperthermia (WBH) in a rat
      model. Breakdown of the BCSFB alters brain homeostasis and adversely affects the
      structure and function of the central nervous system (CNS). Since neurotrophins
      and growth factors (e.g., brain-derived growth factor [BDNF], glial cell line
      derived neurotrophic factor [GDNF], and insulin-like growth factor 1 [IGF-1]) are
      known neuroprotective agents in traumatic and ischemic brain injuries, a
      possibility exists that these neurotrophins will also attenuate neuronal and
      choroidal injury in WBH. Subjection of adult rats to 4 h of WBH at 38 degrees C
      in a biological oxygen demand (BOD) incubator exhibited a profound increase in
      BCSFB permeability to Evans blue and radioiodine. Degeneration of choroidal
      epithelial cells and underlying ependyma, dilatation of the lateral ventricular
      space, and degenerative changes in the adjacent neuropil were frequent. The
      hippocampus, caudate nucleus, thalamus, and hypothalamus showed profound BBB
      disruption and brain edema formation. Intracerebroventricular (i.c.v.)
      administration of BDNF, GDNF, and IGF-1 into the right lateral cerebral ventricle
      (1, 2, or 5 microg in 30 microL, 24 h before WBH) significantly reduced the BCSFB
      and BBB breakdown, brain edema formation, and cellular/tissue injuries. These
      beneficial effects were most pronounced in GDNF- or IGF-1-pretreated animals.
      These novel observations suggest that neurotrophins administered into ventricular
      CSF can attenuate BCSFB and BBB damage following WBH and thereby confer
      neuroprotection. Stabilization of BCSFB function is thus one of the crucial
      factors in achieving neuroprotection in WBH.

PMID- 18077569
TI  - Brain-derived neurotrophic factor in neuronal survival and behavior-related
      plasticity.
AB  - Neurotrophins are critical to the development and maintenance of the mammalian
      central nervous system. Among them is brain-derived neurotrophic factor (BDNF),
      whose synthesis and release is targeted by activation of glutamate receptors.
      Perturbation of this process probably underlies neurodegenerative and psychiatric
      disorders. A naturally occurring variation in humans, in the form of a common
      single-nucleotide polymorphism in the pro region of the polypeptide at codon 66
      (Val66-->Met), affects processing of the pro-BDNF polypeptide and its activation
      dependent release. This variant is associated with differences in the volume of
      the hippocampal formation and with anxiety and depression-related phenotypes.
      Convergent findings supporting a role for BDNF in alterations to hippocampal
      structure and behavior are found in a "humanized" BDNF transgenic mouse. Also,
      recent human genetic studies have supported a role of BDNF signaling in addictive
      behaviors by allele-, genotype-, and haplotype-based association of the TrkB
      gene, which encodes the cognate receptor for BDNF, with alcohol dependence. A
      better understanding of the influence of BDNF-mediated pathways in cell survival
      and plasticity will aid in developing new approaches to restoring normal function
      in disease states.

PMID- 18077570
TI  - Brain-derived neurotrophic factor prevents human immunodeficiency virus type 1
      protein gp120 neurotoxicity in the rat nigrostriatal system.
AB  - Human immunodeficiency virus type 1 (HIV-1) causes neuronal degeneration and, at
      a late stage, creates HIV-associated dementia (HAD) and other neurological
      abnormalities. Therefore, the need for neuroprotective agents is great. However,
      therapeutic agents that reduce HIV neurotoxicity are difficult to characterize
      and develop because rodents are not infected by HIV. This study was undertaken to
      develop an animal model of HIV neurotoxicity by using the HIV-1 envelope
      glycoprotein 120 (gp120). Vehicle or gp120 was injected acutely in the striatum
      of adult rats. gp120 produced loss of nigrostriatal neurons, as shown both by
      histochemical analysis of brain sections for apoptosis and biochemical
      determination of dopamine. The neurotrophin brain-derived neurotrophic factor
      (BDNF) delivered by a recombinant adeno-associated viral vector prevented gp120
      toxicity. This study's results support the notion that gp120 produces a
      widespread neurotoxicity similar to that observed in HIV-positive individuals and
      that BDNF may be a suitable neuroprotective agent for HAD.

PMID- 18077571
TI  - Induction of neurotrophic factors GDNF and BDNF associated with the mechanism of
      neurorescue action of rasagiline and ladostigil: new insights and implications
      for therapy.
AB  - Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common
      neurodegenerative disorders, although there is no drug or therapeutic treatment
      to demonstrate disease-modifying effects. Previous work has proposed that
      neurodegeneration is linked to a lack of trophic support in those neurons and
      brain areas associated with PD and AD. Indeed, previous studies have found that
      neurotrophic factors (NTFs) support neuronal survival in various cellular and
      animal models of PD and AD. Thus, attention has begun to turn to the possibility
      of NTF neuroprotective-neurorescue therapies for these diseases, indicating that
      NTFs may be of significant clinical importance as exogenously supplied or
      endogenously induced elements that obliterate neuronal deficits and degeneration.
      We have recently reported that the anti-PD drug rasagiline, the anti-AD drug
      ladostigil, and their propargyl moiety, propargylamine, enhanced the expression
      levels of brain-derived neurotrophic factor and glial cell line-derived
      neurotrophic factor, endogenous NTFs associated with activation of
      phosphatidylinositol 3-kinase, protein kinase, and mitogen-activated protein
      kinase cell signaling/survival pathways. These studies indicate that the
      induction of NTFs by rasagiline and ladostigil might suppress apoptosis and
      induce neurorescue in neurodegenerative disorders and may support the drugs'
      possible disease-modifying mechanism of action.

PMID- 18077572
TI  - Neuroprotection at the nanolevel--Part I: Introduction to nanoneurosurgery.
AB  - Nanoneurosurgery demands a departure from the traditional "excise what you can
      see and touch" role of neurosurgeons. Moreover, there is a conceptual leap
      necessary for neuroscientists as well as neurosurgeons in developing and applying
      nanotechniques to neurosurgery at the nanolevel. After introducing the realm of
      nanotechnology and some unique properties of nanomaterials, I review several of
      the nanotechniques in development that are most likely to affect neuroprotection
      at the nanolevel. These techniques include quantum dot "nanobarcode" labeling of
      cellular and subcellular entities, as well as nanotechniques for following
      enzymatic reactions in real time. Nanoscaffolds offer mechanical enhancement of
      neurorepair; carbon nanotube electrode arrays can provide nanolevel electrical
      and chemical enhancement. Even traditional "cut and sew" surgery is being taken
      down to the micron, if not nano, level for single axon repair, and the technology
      can use capillaries to deliver therapeutics to virtually any portion of the
      nervous system with greater than pinpoint accuracy. In this report, I use these
      nanotechniques to introduce the multiplex nanodevices under development.

PMID- 18077573
TI  - Neuroprotection at the nanolevel--Part II: Nanodevices for neuromodulation--deep
      brain stimulation and spinal cord injury.
AB  - Nanotechniques presented in this article's companion report are being multiplexed
      into nanodevices that promise to greatly advance our understanding and treatment
      of many nervous system disorders. Current neuromodulation techniques for deep
      brain stimulation have major drawbacks, such as large size (in comparison with
      ideal of small neuron group stimulation), lack of feedback monitoring of brain
      electrical activity, and high electrical current needs. Carbon nanotube
      nanoelectrode arrays address these drawbacks and offer the possibility of
      monitoring neurotransmitter levels at the synapse/neuronal level in real time.
      Such arrays can monitor and modulate electrochemical events occurring among
      neural networks, which should add greatly to our understanding of neuronal
      communication. A multiplex nanodevice for studying (and enhancing) axonal
      regeneration after spinal cord injury is also being developed. The nanotechniques
      described in the companion piece are combined in a micron-sized neural growth
      tube lined with nanodevices through which the regenerating axon extends--allowing
      continuous monitoring and modulation of the axon's electrochemical environment
      plus directional guidance with a biodegradable nanoscaffold. Multifunction
      nanodevices provide opportunities for neuronal (and subneuronal) monitoring and
      modulation that will enhance neuroprotection and neurorepair far beyond the micro
      and macrolevel techniques used heretofore.

PMID- 18077574
TI  - Drug delivery to the spinal cord tagged with nanowire enhances neuroprotective
      efficacy and functional recovery following trauma to the rat spinal cord.
AB  - The possibility that drugs attached to innocuous nanowires enhance their delivery
      within the central nervous system (CNS) and thereby increase their therapeutic
      efficacy was examined in a rat model of spinal cord injury (SCI). Three compounds
      -AP173 (SCI-1), AP713 (SCI-2), and AP364 (SCI-5) (Acure Pharma, Uppsala, Sweden)-
      were tagged with TiO(2)-based nanowires using standard procedure. Normal
      compounds were used for comparison. SCI was produced by making a longitudinal
      incision into the right dorsal horn of the T10-T11 segments under Equithesin
      anesthesia. The compounds, either alone or tagged with nanowires, were applied
      topically within 5 to 10 min after SCI. In these rats, behavioral outcome, blood
      spinal cord barrier (BSCB) permeability, edema formation, and cell injury were
      examined at 5 h after injury. Topical application of normal compounds in high
      quantity (10 microg in 20 microL) attenuated behavioral dysfunction (3 h after
      trauma), edema formation, and cell injury, as well as reducing BSCB permeability
      to Evans blue albumin and (131)I. These beneficial effects are most pronounced
      with AP713 (SCI-2) treatment. Interestingly, when these compounds were
      administered in identical conditions after tagging with nanowires, their
      beneficial effects on functional recovery and spinal cord pathology were further
      enhanced. However, topical administration of nanowires alone did not influence
      trauma-induced spinal cord pathology or motor functions. Taken together, our
      results, probably for the first time, indicate that drug delivery and therapeutic
      efficacy are enhanced when the compounds are administered with nanowires.

PMID- 18077575
TI  - Treatment of neurodegenerative disorders with radical nanomedicine.
AB  - In engineering and materials science, nanotechnology has provided many advances
      that effectively reduce oxidative damage generated by free radical production.
      Despite such advances, there has been little application to biomedical problems.
      Increased oxidative stress and free radical production are associated with
      neurodegenerative conditions, including aging, trauma, Alzheimer's and
      Parkinson's diseases, and many others. The antioxidant properties of cerium oxide
      nanoparticles show promise in the treatment of such diseases. Here, we summarize
      the work on the biological antioxidant actions of cerium oxide nanoparticles in
      extension of cell and organism longevity, protection against free radical insult,
      and protection against trauma-induced neuronal damage. We discuss establishment
      of effective dosing parameters, along with the physicochemical properties that
      regulate the pharmacological action of these new nanomaterials. Taken together,
      these studies suggest that nanotechnology can take pharmacological treatment to a
      new level, with a novel generation of nanopharmaceuticals.

PMID- 18077576
TI  - Neuro- and cardioprotective effects of blockade of nitric oxide action by
      administration of methylene blue.
AB  - Methylene blue (MB), generic name methylthioninium (C(16)H(18)ClN(3) S . 3H(2)O),
      is a blue dye synthesized in 1876 by Heinrich Caro for use as a textile dye and
      used in the laboratory and clinically since the 1890s, with well-known toxicity
      and pharmacokinetics. It has experimentally proven neuroprotective and
      cardioprotective effects in a porcine model of global ischemia-reperfusion in
      experimental cardiac arrest. This effect has been attributed to MB's blocking
      effect on nitric oxide synthase and guanylyl cyclase, the latter blocking the
      synthesis of the second messenger of nitric oxide. The physiological effects
      during reperfusion include stabilization of the systemic circulation without
      significantly increased total peripheral resistance, moderately increased
      cerebral cortical blood flow, a decrease of lipid peroxidation and inflammation,
      and less anoxic tissue injury in the brain and the heart. The last two effects
      are recorded as less increase in plasma concentrations of astroglial protein S
      100beta, as well as troponin I and creatine kinase isoenzyme MB, respectively.

PMID- 18077577
TI  - Effect of methylene blue and related redox dyes on monoamine oxidase activity;
      rat pineal content of N-acetylserotonin, melatonin, and related indoles; and
      righting reflex in melatonin-primed frogs.
AB  - The ability of methylene blue (MB) to inhibit the nitric oxide-induced
      stimulation of N-methyl-D-aspartate receptors has been suggested as a possible
      mechanism of MB's clinical antidepressant action. This study evaluated the
      alternative/additional mechanisms of the antidepressant effect of MB on
      biochemical and behavior levels. Selective inhibition of monoamine oxidase type A
      (MAO-A) is widely accepted as a major mechanism of the clinical antidepressant
      effect. MB and the related redox dyes toluidine blue O (TBO), thionine (TN),
      brilliant cresyl blue (BCB), and toluylene blue (TB) were reversible competitive
      inhibitors of both MAO-A and MAO-B and were highly selective toward MAO-A. TBO
      was the most potent inhibitor, followed by TN, BCB, MB, and TB. The dyes studied
      increased rat pineal N-acetylserotonin (NAS) and melatonin content, in accordance
      with our previous observations of the stimulating effect of selective inhibition
      of MAO-A on pineal melatonin biosynthesis. The redox dyes exerted antidepressant
      like activity in frogs; that is, they suppressed the righting reflex in melatonin
      primed frogs. This study's results indicate that selective inhibition of MAO-A
      might mediate the clinical antidepressant effect of MB through NAS stimulation
      and melatonin biosynthesis.

PMID- 18077578
TI  - Effect of methyl derivatives of dopamine on tumor necrosis factor alpha and lipid
      peroxidation.
AB  - We recently demonstrated that melatonin, N-acetylserotonin (NAS), and N
      acetyldopamine (NAD) attenuate the synthesis of lipopolysaccharide (LPS)
      stimulated tumor necrosis factor-alpha (TNF-alpha) and the generation of oxidant
      radicals. In this study, we examined whether acetyl and methyl derivatives of
      dopamine modulate LPS-stimulated TNF-alpha synthesis and LPS- and iron-induced
      lipid peroxidation. Differentiated THP-1-derived human monocytes were coincubated
      with Escherichia coli and rising concentrations of NAS, NAD, N-methyldopamine
      (NMD), or 4-O-methyldopamine (4-O-MD). After 24 h, TNF-alpha was measured in cell
      supernatants. In addition, lipid peroxidation was induced by adding FeCl(2)
      solution to mouse brain tissue homogenates in the presence of rising
      concentrations of NAS, NAD, NMD, or 4-O-MD. Incubating THP-1-derived monocytes
      with rising concentrations of NAS, NAD, NMD, or 4-O-MD markedly decreased LPS
      stimulated TNF-alpha production, which was dose dependent and on the order of 96%
      98%. Rising concentrations of NMD markedly inhibited lipid peroxidation by 59%
      98%. Our results indicated that the inhibitory effect of NAS, NAD, NMD, or 4-O-MD
      on LPS-induced TNF-alpha production and FeCl(2)-stimulated lipid peroxidation is
      robust and dose dependent.

PMID- 18077579
TI  - Valproate and acetyl-L-carnitine prevent methamphetamine-induced behavioral
      sensitization in mice.
AB  - This study deals with the possible inhibitory role played by acetyl-l-carnitine
      (ALC) against methamphetamine (METH)-induced behavioral sensitization. Because
      valproate (VAL) inhibits the behavioral sensitization exerted by different
      psychostimulants, we investigated ALC's potential to prevent the amplification of
      METH-mediated psychomotor effects. We therefore evaluated the locomotor effects
      of VAL or ALC alone or in combination with METH after acute (day 1) as well as
      repeated (day 7) drug challenge. Finally, to assess the induction of behavioral
      sensitization, we also recorded the METH-mediated locomotor response after 7 days
      of drug suspension (day 15). Results showed that both VAL and ALC prevented the
      METH-induced sensitization. Another interesting observation was the significantly
      higher METH-induced hyperactivity at day 15 (after a 7-day drug-free period),
      indicating that behavioral sensitization developed during the washout period.
      Results also showed that both the acute and repeated coadministration of METH
      with either VAL or ALC inhibited METH-induced hyperactivity. We present different
      hypotheses concerning similar but also peculiar mechanisms that might underlie
      the preventive action of VAL and ALC. These data add to a growing body of
      literature that illustrates the potential of ALC in protecting against the insult
      of dysfunctional mitochondrial metabolism and psychostimulant-mediated
      neurotoxicity. By demonstrating an in vivo action against one of the most abused
      drugs, these results raise the possibility of beneficial effects of ALC in abuse
      behavior.

PMID- 18077580
TI  - N-acetylcysteine attenuates arsenite-induced oxidative injury in dorsal root
      ganglion explants.
AB  - Chronic exposure to arsenic causes health problems, including peripheral
      neuropathy. Oxidative stress is one of the mechanisms underlying arsenic-induced
      neurotoxicity. For this report, we studied the protective effect of N
      acetylcysteine (NAC) on arsenic-induced oxidative injury in dorsal root ganglion
      (DRG) explants. After 24-h incubation, NAC concentration-dependently attenuated
      arsenite-induced depletion in glutathione (GSH) content and increases in the
      ratio of oxidized GSH/reduced GSH (GSSG/GSH ratio) in DRG explants. Furthermore,
      NAC inhibited arsenite-induced elevation in the expression of stress proteins,
      such as heat shock protein 70 and heme oxygenase 1, as well as arsenite-induced
      phosphorylation of p38 mitogen-activated protein kinase. Incubation with NAC
      ameliorated arsenite-induced apoptosis by abolishing both mitochondrial and
      endoplasmic reticulum (ER) pathways. In the mitochondrial pathway, NAC attenuated
      arsenite-induced elevation in Bcl-2 level and cytosolic cytochrome c, as well as
      arsenite-induced reduction in procaspase-3 levels. In the ER pathway, NAC
      suppressed arsenite-induced increases in activating transcription factor 6 and
      C/EBP homologous protein in the nuclear fraction. Furthermore, arsenite-induced
      reductions in procaspase-12 and elevation in BIP and caspase-12, an ER-specific
      enzyme, were prevented after NAC incubation. Taken together, our results
      demonstrate that NAC is neuroprotective against arsenite-induced oxidative injury
      in DRG explants. Furthermore, NAC inhibits arsenite-induced toxicity by
      inhibiting ER and mitochondrion activation. Our data indicate that NAC is
      potentially therapeutic for arsenite-induced peripheral neuropathy.

PMID- 18077581
TI  - Effect of luzindole and other melatonin receptor antagonists on iron- and
      lipopolysaccharide-induced lipid peroxidation in vitro.
AB  - Melatonin and its precursor, N-acetylserotonin (NAS), have been shown in in vivo
      and in vitro studies to inhibit iron- and lipopolysaccharide (LPS)-induced lipid
      peroxidation in rats and mice. Using in vitro studies, we examined whether these
      effects will be affected by the melatonin receptor antagonists luzindole (a
      competitive MT(1)/MT(2) antagonist), DH 97 (MT(2)), prazosin (MT(3)), and 4-P
      PDOT (MT(2)). Lipid peroxidation in the form of malondialdehyde (MDA) was assayed
      by measuring thiobarbituric acid-reactive substances. The antagonists did not
      affect the melatonin and NAS effect on iron- and LPS-induced peroxidation.
      However, luzindole alone, but not the other antagonists, inhibited the iron- and
      LPS-induced peroxidation in the rat brain and kidney homogenates. At a dose of 50
      microM, luzindole reduced iron-induced MDA levels by 80% in the brain and 84% in
      the kidney, whereas LPS-induced MDA levels were reduced by 85% in both brain and
      kidney. A dose of 800 microM prevented lipid peroxidation, bringing the MDA
      levels to values of samples untreated by iron or LPS.

PMID- 18077582
TI  - Antibodies to serotonin attenuate closed head injury induced blood brain barrier
      disruption and brain pathology.
AB  - Closed head injury (CHI) often results in profound brain swelling and instant
      death of the victims due to compression of the vital centers. However, the
      neurochemical basis of edema formation in CHI is still obscure. Previous studies
      from our laboratory show that blockade of serotonin synthesis prior to CHI in a
      rat model attenuates brain edema, indicating a prominent role for serotonin in
      head injury. Thus, neutralization of endogenous serotonin activity and/or
      blocking of its receptors will induce neuroprotection in CHI. Since serotonin has
      more than 14 receptors and selective serotonin antagonists are still not
      available, we used serotonin antiserum to neutralize its in vivo effects before
      or after CHI in a rat model. CHI was produced by an impact of 0.224 N on the
      right parietal skull bone under Equithesin anesthesia by dropping a weight of
      114.6 g from a height of 20 cm through a guide tube. This concussive brain injury
      resulted in blood-brain barrier (BBB) disruption, brain edema formation, and
      volume swelling at 5 h that were most pronounced in the contralateral cerebral
      hemisphere. The plasma and brain serotonin levels were increased several-fold at
      this time. Intracerebroventricular administration of serotonin antiserum (1:20,
      monoclonal) into the left lateral cerebral ventricle (30 microL in PBS) 30 min
      before or 30 min (but not 60 min) after CHI significantly attenuated BBB
      disruption, brain edema formation, volume swelling, and brain pathology. The
      plasma and brain serotonin levels continued to remain high. These observations
      are the first to suggest that antiserum to serotonin when administered into the
      CSF during the early phase of CHI are capable of inducing neuroprotection.

PMID- 18077583
TI  - Rab-mediated endocytosis: linking neurodegeneration, neuroprotection, and
      synaptic plasticity?
AB  - Rab proteins are small GTPases involved in endocytosis and recycling of cell
      surface molecules. Recently they have been implicated in the etiopathogenesis of
      several neurodegenerative disorders including Alzheimer's and Lewy body disease.
      In experiments on organotypic hippocampal cultures, upregulation of Rab protein
      family member Rab5b after group I metabotropic glutamate receptor (mGluR)
      stimulation was associated with reduced neuronal vulnerability to excitotoxic
      injury. This mGluR-mediated neuroprotection was abolished by antisense-induced
      deficiency of Rab5b. Electrophysiological measurements of excitatory synaptic
      transmission in the Schaffer collateral-CA1 pathway revealed that mGluR
      activation that induces neuroprotection also induced long-term depression (LTD)
      of synaptic transmission. Similar to the neuroprotection, Rab5b deficiency
      abolished dihydroxyphenylglycine-induced LTD. Together, these findings support
      the idea that Rab proteins, and the Rab5b protein in particular, may provide a
      link between neurodegenerative disease, neuroprotection, and synaptic plasticity,
      as well as possibly being a useful target for pharmacological interventions.

PMID- 18077584
TI  - The Sf1-related nuclear hormone receptor Hr39 regulates Drosophila female
      reproductive tract development and function.
AB  - The vertebrate nuclear hormone receptor steroidogenic factor 1 (SF1; NR5A1)
      controls reproductive development and regulates the transcription of steroid
      modifying cytochrome P450 genes. We find that the SF1-related Drosophila nuclear
      hormone receptor HR39 is also essential for sexual development. In Hr39 mutant
      females, the sperm-storing spermathecae and glandular parovaria are absent or
      defective, causing sterility. Our results indicate that spermathecae and
      parovaria secrete reproductive tract proteins required for sperm maturation and
      function, like the mammalian epididymis and female reproductive tract. Hr39
      controls the expression of specific cytochrome P450 genes and is required in
      females both to activate spermathecal secretion and repress male-specific
      courtship genes such as takeout. Thus, a pathway that, in vertebrates, controls
      sex-specific steroid hormone production, also mediates reproductive functions in
      an invertebrate. Our findings suggest that Drosophila can be used to model more
      aspects of mammalian reproductive biology than previously believed.

PMID- 18077585
TI  - An FGF signaling loop sustains the generation of differentiated progeny from stem
      cells in mouse incisors.
AB  - Rodent incisors grow throughout adult life, but are prevented from becoming
      excessively long by constant abrasion, which is facilitated by the absence of
      enamel on one side of the incisor. Here we report that loss-of-function of
      sprouty genes, which encode antagonists of receptor tyrosine kinase signaling,
      leads to bilateral enamel deposition, thus impeding incisor abrasion and
      resulting in unchecked tooth elongation. We demonstrate that sprouty genes
      function to ensure that enamel-producing ameloblasts are generated on only one
      side of the tooth by inhibiting the formation of ectopic ameloblasts from self
      renewing stem cells, and that they do so by preventing the establishment of an
      epithelial-mesenchymal FGF signaling loop. Interestingly, although inactivation
      of Spry4 alone initiates ectopic ameloblast formation in the embryo, the dosage
      of another sprouty gene must also be reduced to sustain it after birth. These
      data reveal that the generation of differentiated progeny from a particular stem
      cell population can be differently regulated in the embryo and adult.

PMID- 18077586
TI  - Bud specific N-sulfation of heparan sulfate regulates Shp2-dependent FGF
      signaling during lacrimal gland induction.
AB  - Preferential outgrowth of the bud cells forms the basis of branching
      morphogenesis. Here, we show that lacrimal gland development requires specific
      modification of heparan sulfates by Ndst genes at the tip of the lacrimal gland
      bud. Systemic and conditional knockout experiments demonstrate the tissue
      specific requirement of Ndst1 and Ndst2 in the lacrimal gland epithelial, but not
      mesenchymal, cells, and the functional importance of Ndst1 in Fgf10-Fgfr2b, but
      not of Fgf1-Fgfr2b, complex formation. Consistent with this, Fgf10-induced
      ectopic lacrimal gland budding in explant cultures is dependent upon Ndst gene
      dose, and epithelial deletion of Fgfr2 abolishes lacrimal gland budding, its
      specific modification of heparan sulfate and its phosphorylation of Shp2 (Ptpn11 
      Mouse Genome Informatics). Finally, we show that genetic ablation of Ndst1,
      Fgfr2 or Shp2 disrupts ERK signaling in lacrimal gland budding. Given the
      evolutionarily conserved roles of these genes, the localized activation of the
      Ndst-Fgfr-Shp2 genetic cascade is probably a general regulatory mechanism of FGF
      signaling in branching morphogenesis.

PMID- 18077587
TI  - FGF signals guide migration of mesenchymal cells, control skeletal morphogenesis
      [corrected] and regulate gastrulation during sea urchin development.
AB  - The sea urchin embryo is emerging as an attractive model to study morphogenetic
      processes such as directed migration of mesenchyme cells and cell sheet
      invagination, but surprisingly, few of the genes regulating these processes have
      yet been characterized. We present evidence that FGFA, the first FGF family
      member characterized in the sea urchin, regulates directed migration of
      mesenchyme cells, morphogenesis of the skeleton and gastrulation during early
      development. We found that at blastula stages, FGFA and a novel putative FGF
      receptor are expressed in a pattern that prefigures morphogenesis of the
      skeletogenic mesoderm and that suggests that FGFA is one of the elusive signals
      that guide migration of primary mesenchyme cells (PMCs). We first show that fgfA
      expression is correlated with abnormal migration and patterning of the PMCs
      following treatments that perturb specification of the ectoderm along the oral
      aboral and animal-vegetal axes. Specification of the ectoderm initiated by Nodal
      is required to restrict fgfA to the lateral ectoderm, and in the absence of
      Nodal, fgfA is expressed ectopically throughout most of the ectoderm. Inhibition
      of either FGFA, FGFR1 or FGFR2 function severely affects morphogenesis of the
      skeleton. Furthermore, inhibition of FGFA and FGFR1 signaling dramatically delays
      invagination of the archenteron, prevents regionalization of the gut and
      abrogates formation of the stomodeum. We identified several genes acting
      downstream of fgfA in these processes, including the transcription factors pea3
      and pax2/5/8 and the signaling molecule sprouty in the lateral ectoderm and SM30
      and SM50 in the primary mesenchyme cells. This study identifies the FGF signaling
      pathway as an essential regulator of gastrulation and directed cell migration in
      the sea urchin embryo and as a key player in the gene regulatory network
      directing morphogenesis of the skeleton.

PMID- 18077588
TI  - Initiation of Wnt signaling: control of Wnt coreceptor Lrp6
      phosphorylation/activation via frizzled, dishevelled and axin functions.
AB  - Canonical Wnt/beta-catenin signaling has central roles in development and
      diseases, and is initiated by the action of the frizzled (Fz) receptor, its
      coreceptor LDL receptor-related protein 6 (Lrp6), and the cytoplasmic dishevelled
      (Dvl) protein. The functional relationships among Fz, Lrp6 and Dvl have long been
      enigmatic. We demonstrated previously that Wnt-induced Lrp6 phosphorylation via
      glycogen synthase kinase 3 (Gsk3) initiates Wnt/beta-catenin signaling. Here we
      show that both Fz and Dvl functions are critical for Wnt-induced Lrp6
      phosphorylation through Fz-Lrp6 interaction. We also show that axin, a key
      scaffolding protein in the Wnt pathway, is required for Lrp6 phosphorylation via
      its ability to recruit Gsk3, and inhibition of Gsk3 at the plasma membrane blocks
      Wnt/beta-catenin signaling. Our results suggest a model that upon Wnt-induced Fz
      Lrp6 complex formation, Fz recruitment of Dvl in turn recruits the axin-Gsk3
      complex, thereby promoting Lrp6 phosphorylation to initiate beta-catenin
      signaling. We discuss the dual roles of the axin-Gsk3 complex and signal
      amplification by Lrp6-axin interaction during Wnt/beta-catenin signaling.

PMID- 18077589
TI  - Eomesodermin, a target gene of Pou4f2, is required for retinal ganglion cell and
      optic nerve development in the mouse.
AB  - The mechanisms regulating retinal ganglion cell (RGC) development are crucial for
      retinogenesis and for the establishment of normal vision. However, these
      mechanisms are only vaguely understood. RGCs are the first neuronal lineage to
      segregate from pluripotent progenitors in the developing retina. As output
      neurons, RGCs display developmental features very distinct from those of the
      other retinal cell types. To better understand RGC development, we have
      previously constructed a gene regulatory network featuring a hierarchical cascade
      of transcription factors that ultimately controls the expression of downstream
      effector genes. This has revealed the existence of a Pou domain transcription
      factor, Pou4f2, that occupies a key node in the RGC gene regulatory network and
      that is essential for RGC differentiation. However, little is known about the
      genes that connect upstream regulatory genes, such as Pou4f2 with downstream
      effector genes responsible for RGC differentiation. The purpose of this study was
      to characterize the retinal function of eomesodermin (Eomes), a T-box
      transcription factor with previously unsuspected roles in retinogenesis. We show
      that Eomes is expressed in developing RGCs and is a mediator of Pou4f2 function.
      Pou4f2 directly regulates Eomes expression through a cis-regulatory element
      within a conserved retinal enhancer. Deleting Eomes in the developing retina
      causes defects reminiscent of those in Pou4f2(-/-) retinas. Moreover, myelin
      ensheathment in the optic nerves of Eomes(-/-) embryos is severely impaired,
      suggesting that Eomes regulates this process. We conclude that Eomes is a crucial
      regulator positioned immediately downstream of Pou4f2 and is required for RGC
      differentiation and optic nerve development.

PMID- 18077590
TI  - Common functions of central and posterior Hox genes for the repression of head in
      the trunk of Drosophila.
AB  - Hox genes are localised in complexes, encode conserved homeodomain transcription
      factors and have mostly been studied for their specialised functions: the
      formation of distinct structures along the anteroposterior axis. They probably
      derived via duplication followed by divergence, from a unique gene, suggesting
      that Hox genes may have retained a common function. The comparison of their
      homeodomain sequences groups Hox proteins into Anterior, Central and Posterior
      classes, reflecting their expression patterns in the head, trunk and tail,
      respectively. However, functional data supporting this classification are rare.
      Here, we re-examine a common activity of Hox genes in Drosophila: the repression
      of head in the trunk. First, we show that central and posterior Hox genes prevent
      the expression of the head specific gene optix in the trunk, providing a
      functional basis for the classification. Loss-of-function mutations of optix
      affect embryonic head development, whereas ectopic Optix expression strongly
      perturbs trunk development. Second, we demonstrate that the non-Hox genes
      teashirt, extradenticle and homothorax are required for the repression of optix
      and that Wingless signalling and Engrailed contribute to this repression. We
      propose that an evolutionary early function of Hox genes was to modify primitive
      head morphology with novel functions specialising the trunk appearing later on.

PMID- 18077592
TI  - Drosophila eggshell is patterned by sequential action of feedforward and feedback
      loops.
AB  - During Drosophila oogenesis, patterning activities of the EGFR and Dpp pathways
      specify several subpopulations of the follicle cells that give rise to dorsal
      eggshell structures. The roof of dorsal eggshell appendages is formed by the
      follicle cells that express Broad (Br), a zinc-finger transcription factor
      regulated by both pathways. EGFR induces Br in the dorsal follicle cells. This
      inductive signal is overridden in the dorsal midline cells, which are exposed to
      high levels of EGFR activation, and in the anterior cells, by Dpp signaling. We
      show that the resulting changes in the Br pattern affect the expression of Dpp
      receptor thickveins (tkv), which is essential for Dpp signaling. By controlling
      tkv, Br controls Dpp signaling in late stages of oogenesis and, as a result,
      regulates its own repression in a negative-feedback loop. We synthesize these
      observations into a model, whereby the dynamics of Br expression are driven by
      the sequential action of feedforward and feedback loops. The feedforward loop
      controls the spatial pattern of Br expression, while the feedback loop modulates
      this pattern in time. This mechanism demonstrates how complex patterns of gene
      expression can emerge from simple inputs, through the interaction of regulatory
      network motifs.

PMID- 18077591
TI  - A role for S1P signalling in axon guidance in the Xenopus visual system.
AB  - Sphingosine 1-phosphate (S1P), a lysophospholipid, plays an important chemotactic
      role in the migration of lymphocytes and germ cells, and is known to regulate
      aspects of central nervous system development such as neurogenesis and neuronal
      migration. Its role in axon guidance, however, has not been examined. We show
      that sphingosine kinase 1, an enzyme that generates S1P, is expressed in areas
      surrounding the Xenopus retinal axon pathway, and that gain or loss of S1P
      function in vivo causes errors in axon navigation. Chemotropic assays reveal that
      S1P elicits fast repulsive responses in retinal growth cones. These responses
      require heparan sulfate, are sensitive to inhibitors of proteasomal degradation,
      and involve RhoA and LIM kinase activation. Together, the data identify
      downstream components that mediate S1P-induced growth cone responses and
      implicate S1P signalling in axon guidance.

PMID- 18077593
TI  - Position fine-tuning of caudal primary motoneurons in the zebrafish spinal cord.
AB  - In zebrafish embryos, each myotome is typically innervated by three primary
      motoneurons (PMNs): the caudal primary (CaP), middle primary (MiP) and rostral
      primary (RoP). PMN axons first exit the spinal cord through a single exit point
      located at the midpoint of the overlying somite, which is formed beneath the CaP
      cell body and is pioneered by the CaP axon. However, the placement of CaP cell
      bodies with respect to corresponding somites is poorly understood. Here, we
      determined the early events in CaP cell positioning using neuropilin 1a
      (nrp1a):gfp transgenic embryos in which CaPs were specifically labeled with GFP.
      CaP cell bodies first exhibit an irregular pattern in presence of newly formed
      corresponding somites and then migrate to achieve their proper positions by
      axonogenesis stages. CaPs are generated in excess compared with the number of
      somites, and two CaPs often overlap at the same position through this process.
      Next, we showed that CaP cell bodies remain in the initial irregular positions
      after knockdown of Neuropilin1a, a component of the class III semaphorin
      receptor. Irregular CaP position frequently results in aberrant double exit
      points of motor axons, and secondary motor axons form aberrant exit points
      following CaP axons. Its expression pattern suggests that sema3ab regulates the
      CaP position. Indeed, irregular CaP positions and exit points are induced by
      Sema3ab knockdown, whose ectopic expression can alter the position of CaP cell
      bodies. Results suggest that Semaphorin-Neuropilin signaling plays an important
      role in position fine-tuning of CaP cell bodies to ensure proper exit points of
      motor axons.

PMID- 18077594
TI  - The zebrafish mutant lbk/vam6 resembles human multisystemic disorders caused by
      aberrant trafficking of endosomal vesicles.
AB  - The trafficking of intracellular vesicles is essential for a number of cellular
      processes and defects in this process have been implicated in a wide range of
      human diseases. We identify the zebrafish mutant lbk as a novel model for such
      disorders. lbk displays hypopigmentation of skin melanocytes and the retinal
      pigment epithelium (RPE), an absence of iridophore reflections, defects in
      internal organs (liver, intestine) as well as functional defects in vision and
      the innate immune system (macrophages). Positional cloning, an allele screen,
      rescue experiments and morpholino knock-down reveal a mutation in the zebrafish
      orthologue of the vam6/vps39 gene. Vam6p is part of the HOPS complex, which is
      essential for vesicle tethering and fusion. Affected cells in the lbk RPE, liver,
      intestine and macrophages display increased numbers and enlarged intracellular
      vesicles. Physiological and behavioural analyses reveal severe defects in visual
      ability in lbk mutants. The present study provides the first phenotypic
      description of a lack of vam6 gene function in a multicellular organism. lbk
      shares many of the characteristics of human diseases and suggests a novel disease
      gene for pathologies associated with defective vesicle transport, including the
      arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, the Hermansky-Pudlak
      syndrome, the Chediak-Higashi syndrome and the Griscelli syndrome.

PMID- 18077595
TI  - Delineating the contributions of AT1a and AT1b receptor-mediated uptake of ANG II
      in kidneys and adrenals.

PMID- 18077596
TI  - Intracrystalline urinary proteins facilitate degradation and dissolution of
      calcium oxalate crystals in cultured renal cells.
AB  - We have previously proposed that intracrystalline proteins would increase
      intracellular proteolytic disruption and dissolution of calcium oxalate (CaOx)
      crystals. Chauvet MC, Ryall RL. J Struct Biol 151: 12-17, 2005; Fleming DE, van
      Riessen A, Chauvet MC, Grover PK, Hunter B, van Bronswijk W, Ryall RL. J Bone
      Miner Res 18: 1282-1291, 2003; Ryall RL, Fleming DE, Doyle IR, Evans NA, Dean CJ,
      Marshall VR. J Struct Biol 134: 5-14, 2001. The aim of this investigation was to
      determine the effect of increasing concentrations of intracrystalline protein on
      the rate of CaOx crystal dissolution in Madin-Darby canine kidney (MDCKII) cells.
      Crystal matrix extract (CME) was isolated from urinary CaOx monohydrate (COM)
      crystals. Cold and [14C]oxalate-labeled COM crystals were precipitated from
      ultrafiltered urine containing 0-5 mg/l CME. Crystal surface area was estimated
      from scanning electron micrographs, and synchrotron X-ray diffraction was used to
      determine nonuniform strain and crystallite size. Radiolabeled crystals were
      added to MDCKII cells and crystal dissolution, expressed as radioactive label
      released into the medium, was measured. Increasing CME content did not
      significantly alter crystal surface area. However, nonuniform strain increased
      and crystallite size decreased in a dose-response manner, both reaching
      saturation at a CME concentration of 3 mg/ and demonstrating unequivocally the
      inclusion of increasing quantities of proteins in the crystals. This was
      confirmed by Western blotting. Crystal dissolution also followed saturation
      kinetics, increasing proportionally with final CME concentration and reaching a
      plateau at a concentration of approximately 2 mg/l. These findings were
      complemented by field emission scanning electron microscopy, which showed that
      crystal degradation also increased relative to CME concentration.
      Intracrystalline proteins enhance degradation and dissolution of CaOx crystals
      and thus may constitute a natural defense against urolithiasis. The findings have
      significant ramifications in biomineral metabolism and pathogenesis of renal
      stones.

PMID- 18077597
TI  - Melatonin ameliorates oxidative stress, inflammation, proteinuria, and
      progression of renal damage in rats with renal mass reduction.
AB  - The progressive deterioration of renal function and structure resulting from
      renal mass reduction are mediated by a variety of mechanisms, including oxidative
      stress and inflammation. Melatonin, the major product of the pineal gland, has
      potent_antioxidant and anti-inflammatory properties, and its production is
      impaired in chronic renal failure. We therefore investigated if melatonin
      treatment would modify the course of chronic renal failure in the remnant kidney
      model. We studied rats followed 12 wk after renal ablation untreated (Nx group, n
      = 7) and treated with melatonin administered in the drinking water (10 mg/100 ml)
      (Nx + MEL group, n = 8). Sham-operated rats (n = 10) were used as controls.
      Melatonin administration increased 13-15 times the endogenous hormone levels.
      Rats in the Nx + MEL group had reduced oxidative stress (malondialdehyde levels
      in plasma and in the remnant kidney as well as nitrotyrosine renal abundance) and
      renal inflammation (p65 nuclear factor-kappaB-positive renal interstitial cells
      and infiltration of lymphocytes and macrophages). Collagen, alpha-smooth muscle
      actin, and transforming growth factor-beta renal abundance were all increased in
      the remnant kidney of the untreated rats and were reduced significantly by
      melatonin treatment. Deterioration of renal function (plasma creatinine and
      proteinuria) and structure (glomerulosclerosis and tubulointerstitial damage)
      resulting from renal ablation were ameliorated significantly with melatonin
      treatment. In conclusion, melatonin administration improves the course of chronic
      renal failure in rats with renal mass reduction. Further studies are necessary to
      define the potential usefulness of this treatment in other animal models and in
      patients with chronic renal disease.

PMID- 18077598
TI  - Hypothalamic paraventricular nucleus is critical for renal vasoconstriction
      elicited by elevations in body temperature.
AB  - Redistribution of blood from the viscera to the peripheral vasculature is the
      major cardiovascular response designed to restore thermoregulatory homeostasis
      after an elevation in body core temperature. In this study, we investigated the
      role of the hypothalamic paraventricular nucleus (PVN) in the reflex decrease in
      renal blood flow that is induced by hyperthermia, as this brain region is known
      to play a key role in renal function and may contribute to the central pathways
      underlying thermoregulatory responses. In anesthetized rats, blood pressure,
      heart rate, renal blood flow, and tail skin temperature were recorded in response
      to elevating body core temperature. In the control group, saline was
      microinjected bilaterally into the PVN; in the second group, muscimol (1 nmol in
      100 nl per side) was microinjected to inhibit neuronal activity in the PVN; and
      in a third group, muscimol was microinjected outside the PVN. Compared with
      control, microinjection of muscimol into the PVN did not significantly affect the
      blood pressure or heart rate responses. However, the normal reflex reduction in
      renal blood flow observed in response to hyperthermia in the control group (
      approximately 70% from a resting level of 11.5 ml/min) was abolished by the
      microinjection of muscimol into the PVN (maximum reduction of 8% from a resting
      of 9.1 ml/min). This effect was specific to the PVN since microinjection of
      muscimol outside the PVN did not prevent the normal renal blood flow response.
      The data suggest that the PVN plays an essential role in the reflex decrease in
      renal blood flow elicited by hyperthermia.

PMID- 18077600
TI  - Dipeptidyl peptidase IV inhibition downregulates Na+ - H+ exchanger NHE3 in rat
      renal proximal tubule.
AB  - In the microvillar microdomain of the kidney brush border, sodium hydrogen
      exchanger type 3 (NHE3) exists in physical complexes with the serine protease
      dipeptidyl peptidase IV (DPPIV). The purpose of this study was to explore the
      functional relationship between NHE3 and DPPIV in the intact proximal tubule in
      vivo. To this end, male Wistar rats were treated with an injection of the
      reversible DPPIV inhibitor Lys [Z(NO2)]-pyrrolidide (I40; 60 mg.kg(-1).day(-1)
      ip) for 7 days. Rats injected with equal amounts of the noninhibitory compound
      Lys[Z(NO2)]-OH served as controls. Na(+) - H(+) exchange activity in isolated
      microvillar membrane vesicles was 45 +/- 5% decreased in rats treated with I40.
      Membrane fractionation studies using isopycnic centrifugation revealed that I40
      provoked redistribution of NHE3 along with a small fraction of DPPIV from the
      apical enriched microvillar membranes to the intermicrovillar microdomain of the
      brush border. I40 significantly increased urine output (67 +/- 9%; P < 0.01),
      fractional sodium excretion (63 +/- 7%; P < 0.01), as well as lithium clearance
      (81 +/- 9%; P < 0.01), an index of end-proximal tubule delivery. Although not
      significant, a tendency toward decreased blood pressure and plasma pH/HCO(3)(-)
      was noted in I40-treated rats. These findings indicate that inhibition of DPPIV
      catalytic activity is associated with inhibition of NHE3-mediated NaHCO3
      reabsorption in rat renal proximal tubule. Inhibition of apical Na(+) - H(+)
      exchange is due to reduced abundance of NHE3 protein in the microvillar
      microdomain of the kidney brush border. Moreover, this study demonstrates a
      physiologically significant interaction between NHE3 and DPPIV in the intact
      proximal tubule in vivo.

PMID- 18077599
TI  - Akt activation improves oxidative phosphorylation in renal proximal tubular cells
      following nephrotoxicant injury.
AB  - Previously, we showed that protein kinase B (Akt) activation increases
      intracellular ATP levels and decreases necrosis in renal proximal tubular cells
      (RPTC) injured by the nephrotoxicant S-(1, 2-dichlorovinyl)-l-cysteine (DCVC)
      (Shaik ZP, Fifer EK, Nowak G. Am J Physiol Renal Physiol 292: F292-F303, 2007).
      This study examined the role of Akt in improving mitochondrial function in DCVC
      injured RPTC. Our data show a novel observation that phosphorylated (active) Akt
      is localized in mitochondria of noninjured RPTC, both in mitoplasts and the
      mitochondrial outer membrane. Mitochondrial levels of active Akt decreased in
      nephrotoxicant-injured RPTC, and this decrease was associated with mitochondrial
      dysfunction. DCVC decreased basal, uncoupled, and state 3 respirations; ATP
      production; activities of complexes I, II, and III; the mitochondrial membrane
      potential (DeltaPsi(m)); and F(0)F(1)-ATPase activity. Expressing constitutively
      active Akt in DCVC-injured RPTC increased the levels of phosphorylated Akt in
      mitochondria, reduced the decreases in basal and uncoupled respirations,
      increased complex I-coupled state 3 respiration and ATP production, enhanced
      activities of complex I, complex III, and F(0)F(1)-ATPase, and improved
      DeltaPsi(m). In contrast, inhibiting Akt activation by expressing dominant
      negative (inactive) Akt or using 20 microM LY294002 exacerbated decreases in
      electron transport rate, state 3 respiration, ATP production, DeltaPsi(m), and
      activities of complex I, complex III, and F(0)F(1)-ATPase. In conclusion, our
      data show that Akt activation promotes mitochondrial respiration and ATP
      production in toxicant-injured RPTC by 1) improving integrity of the respiratory
      chain and maintaining activities of complex I and complex III, 2) reducing
      decreases in DeltaPsi(m), and 3) restoring F(0)F(1)-ATPase activity.

PMID- 18077601
TI  - Amelioration of anti-Thy1-glomerulonephritis by PPAR-gamma agonism without
      increase of endothelial progenitor cell homing.
AB  - Impaired glomerular endothelial integrity is pivotal in various renal diseases
      and depends on both the degree of glomerular endothelial injury and the
      effectiveness of glomerular endothelial repair. Glomerular endothelial repair is,
      in part, mediated by bone marrow-derived endothelial progenitor cells. Peroxisome
      proliferator activated receptor-gamma (PPAR-gamma) agonists have therapeutic
      actions independent of their insulin-sensitizing effects, including enhancement
      of endothelial progenitor cell function and differentiation. We evaluated the
      effect of PPAR-gamma agonist rosiglitazone (4 mg.kg(-1).day(-1)) on the course of
      anti-Thy1-glomerulonephritis in rats. Rosiglitazone limited the development of
      proteinuria and prevented plasma urea elevation (8.1 +/- 0.4 vs. 12.5 +/- 1.1
      mmol/l, P = 0.002). Histologically, inflammatory cell influx was not affected,
      but rosiglitazone-treated rats did show fewer microaneurysmatic glomeruli on day
      7 (26 +/- 3 vs. 41 +/- 5%, P = 0.01) and reduced activation of matrix production
      with reduced renal cortical transforming growth factor-beta, plasminogen
      activator inhibitor type 1, and fibronectin-1 mRNA expression. However, bone
      marrow-derived endothelial cell glomerular incorporation was not enhanced (3.1 +/
      0.4 vs. 3.6 +/- 0.3 cells/glomerular cross section; P = 0.31). Rosiglitazone
      treatment in nonnephritic rats did not influence proteinuria, urea, or renal
      histology. In conclusion, treatment with PPAR-gamma agonist rosiglitazone
      ameliorates the course of experimental glomerulonephritis in a nondiabetic model,
      but not through enhancing incorporation of bone marrow-derived endothelial cells
      in the glomerulus.

PMID- 18077602
TI  - Regulation of apical NHE3 trafficking by ouabain-induced activation of the
      basolateral Na+-K+-ATPase receptor complex.
AB  - The long-term effects of ouabain on transepithelial Na(+) transport involve
      transcriptional downregulation of apical Na(+)/H(+) exchanger isoform 3 (NHE3).
      The aim of this study was to determine whether ouabain could acutely regulate
      NHE3 via a posttranscriptional mechanism in LLC-PK1 cells. We observed that the
      basolateral, but not apical, application of ouabain for 1 h significantly reduced
      transepithelial Na(+) transport. This effect was not due to changes in the
      integrity of tight junctions or increases in the intracellular Na(+)
      concentration. Ouabain regulated the trafficking of NHE3 and subsequently
      inhibited its activity, a process independent of intracellular Na(+)
      concentration. Ouabain-induced NHE3 trafficking was abolished by either
      cholesterol depletion or Src inhibition. Moreover, ouabain increased the
      intracellular Ca(2+) concentration. Pretreatment of cells with the intracellular
      Ca(2+) chelator BAPTA-AM blocked ouabain-induced trafficking of NHE3. Also,
      blockade of Na(+)-K(+)-ATPase endocytosis by a phosphatidylinositol 3-kinase
      inhibitor was equally effective in attenuating ouabain-induced NHE3 trafficking.
      These data indicate that ouabain acutely stimulates NHE3 trafficking by
      activating the basolateral Na(+)-K(+)-ATPase signaling complex. Taken together
      with our previous observations, we propose that ouabain can simultaneously
      regulate basolateral Na(+)-K(+)-ATPase and apical NHE3, leading to inhibition of
      transepithelial Na(+) transport. This mechanism may be relevant to proximal
      tubular Na(+) handling during conditions associated with increases in circulating
      endogenous cardiotonic steroids.

PMID- 18077603
TI  - Mitochondrial DNA damage triggers mitochondrial-superoxide generation and
      apoptosis.
AB  - Recently, it has become apparent that mitochondrial DNA (mtDNA) damage can
      rapidly initiate apoptosis independent of mutations, although the mechanism
      involved remains unclear. To elucidate this mechanism, angiotensin II-mediated
      apoptosis was studied in cells that were transduced with a lentiviral vector to
      overexpress the DNA repair enzyme 8-oxoguanine glycosylase or were treated with
      inhibitors known to block angiotensin II-induced mtDNA damage. Cells exhibiting
      angiotensin II-induced mtDNA damage showed two phases of superoxide generation,
      the first derived from NAD(P)H oxidase and the second of mitochondrial origin,
      whereas cells prevented from experiencing mtDNA damage importantly exhibited only
      the first phase. Furthermore, cells with mtDNA damage demonstrated impairments in
      mitochondrial protein expression, cellular respiration, and complex 1 activity
      before the onset of the second phase of oxidation. After the second phase, the
      mitochondrial membrane potential collapsed, cytochrome c was released, and the
      cells underwent apoptosis, all of which were prevented by disrupting mtDNA
      damage. Collectively, these data reveal a novel mechanism of apoptosis that is
      initiated when mtDNA damage triggers mitochondrial superoxide generation and
      ultimately the activation of the mitochondrial permeability transition. This
      novel mechanism may play an important pathological role.

PMID- 18077604
TI  - Recovery of skeletal muscle mass after extensive injury: positive effects of
      increased contractile activity.
AB  - The present study was designed to test the hypothesis that increasing physical
      activity by running exercise could favor the recovery of muscle mass after
      extensive injury and to determine the main molecular mechanisms involved. Left
      soleus muscles of female Wistar rats were degenerated by notexin injection before
      animals were assigned to either a sedentary group or an exercised group. Both
      regenerating and contralateral intact muscles from active and sedentary rats were
      removed 5, 7, 14, 21, 28 and 42 days after injury (n = 8 rats/group). Increasing
      contractile activity through running exercise during muscle regeneration ensured
      the full recovery of muscle mass and muscle cross-sectional area as soon as 21
      days after injury, whereas muscle weight remained lower even 42 days postinjury
      in sedentary rats. Proliferator cell nuclear antigen and MyoD protein expression
      went on longer in active rats than in sedentary rats. Myogenin protein expression
      was higher in active animals than in sedentary animals 21 days postinjury. The
      Akt-mammalian target of rapamycin (mTOR) pathway was activated early during the
      regeneration process, with further increases of mTOR phosphorylation and its
      downstream effectors, eukaryotic initiation factor-4E-binding protein-1 and
      p70(s6k), in active rats compared with sedentary rats (days 7-14). The exercise
      induced increase in mTOR phosphorylation, independently of Akt, was associated
      with decreased levels of phosphorylated AMP-activated protein kinase. Taken
      together, these results provided evidence that increasing contractile activity
      during muscle regeneration ensured early and full recovery of muscle mass and
      suggested that these beneficial effects may be due to a longer proliferative step
      of myogenic cells and activation of mTOR signaling, independently of Akt, during
      the maturation step of muscle regeneration.

PMID- 18077605
TI  - ClC-3 is required for LPA-activated Cl- current activity and fibroblast-to
      myofibroblast differentiation.
AB  - To determine the effects of chloride channel 3 (ClC-3) knockdown and
      overexpression on lysophosphatidic acid (LPA)- and volume-regulated anion channel
      Cl(-) currents (I(Cl,LPA) and I(Cl,VRAC), respectively), cell differentiation,
      and cell volume regulation, a short hairpin RNA (shRNA) expression system based
      on a mouse U6 promoter was used to knock down ClC-3 in human corneal keratocytes
      and human fetal lung fibroblasts. ClC-3 overexpression was achieved by
      electroporating full-length ClC-3, within a pcDNA3.1 vector, into these two cell
      lines. RT-PCR and Western blot analysis were used to detect ClC-3 mRNA and
      protein levels. Whole cell perforated patch-clamp recording was used to measure
      I(Cl,LPA) and I(Cl,VRAC) currents, and fluorescence-activated cell sorting
      analysis was used to measure cell volume regulation. ClC-3 knockdown
      significantly decreased I(Cl,LPA) and I(Cl,VRAC) activity in the presence of
      transforming growth factor-beta(1) (TGF-beta(1)) compared with controls, whereas
      ClC-3 overexpression resulted in increased I(Cl,LPA) activity in the absence of
      TGF-beta(1). ClC-3 knockdown also resulted in a reduction of alpha-smooth muscle
      actin (alpha-SMA) protein levels in the presence of TGF-beta(1), whereas ClC-3
      overexpression increased alpha-SMA protein expression in the absence of TGF
      beta(1). In addition, keratocytes transfected with ClC-3 shRNA had a
      significantly blunted regulatory volume decrease response following hyposmotic
      stimulation compared with controls. These data confirm that ClC-3 is important in
      VRAC function and cell volume regulation, is associated with the I(Cl,LPA)
      current activity, and participates in the fibroblast-to-myofibroblast transition.

PMID- 18077606
TI  - Antibody-independent localization of the electroneutral Na+-HCO3- cotransporter
      NBCn1 (slc4a7) in mice.
AB  - The expression pattern of the electroneutral Na(+)-HCO(3)(-)cotransporter NBCn1
      (slc4a7) was investigated by beta-galactosidase staining of mice with a LacZ
      insertion into the NBCn1 gene. This method is of particular value because it is
      independent of immunoreactivity. We find that the NBCn1 promoter is active in a
      number of tissues where NBCn1 has previously been functionally or
      immunohistochemically identified, including a broad range of blood vessels
      (vascular smooth muscle cells and endothelial cells), kidney thick ascending limb
      and medullary collecting duct epithelial cells, the epithelial lining of the
      kidney pelvis, duodenal enterocytes, choroid plexus epithelial cells,
      hippocampus, and retina. Kidney corpuscles, colonic mucosa, and nonvascular
      smooth muscle cells (from the urinary bladder, trachea, gastrointestinal wall,
      and uterus) were novel areas of promoter activity. Atrial but not ventricular
      cardiomyocytes were stained. In the brain, distinct layers of the cerebral cortex
      and cerebellar Purkinje cells were stained as was the dentate nucleus. No
      staining of skeletal muscle or cortical collecting ducts was observed. RT-PCR
      analyses confirmed the expression of NBCn1 and beta-galactosidase in selected
      tissues. Disruption of the NBCn1 gene resulted in reduced NBCn1 expression, and
      in bladder smooth muscle cells, reduced amiloride-insensitive Na(+)-dependent
      HCO(3)(-) influx was observed. Furthermore, disruption of the NBCn1 gene resulted
      in a lower intracellular steady-state pH of bladder smooth muscle cells in the
      presence of CO(2)/HCO(3)(-) but not in its nominal absence. We conclude that
      NBCn1 has a broad expression profile, supporting previous findings based on
      immunoreactivity, and suggest several new tissues where NBCn1 may be important.

PMID- 18077607
TI  - Phosphorylation of GRK2 by PKA augments GRK2-mediated phosphorylation,
      internalization, and desensitization of VPAC2 receptors in smooth muscle.
AB  - The smooth muscle of the gut expresses mainly G(s) protein-coupled vasoactive
      intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide receptors
      (VPAC(2) receptors), which belong to the secretin family of G protein-coupled
      receptors. The extent to which PKA and G protein-coupled receptor kinases (GRKs)
      participate in homologous desensitization varies greatly among the secretin
      family of receptors. The present study identified the novel role of PKA in
      homologous desensitization of VPAC(2) receptors via the phosphorylation of GRK2
      at Ser(685). VIP induced phosphorylation of GRK2 in a concentration-dependent
      fashion, and the phosphorylation was abolished by blockade of PKA with cell
      permeable myristoylated protein kinase inhibitor (PKI) or in cells expressing PKA
      phosphorylation-site deficient GRK2(S685A). Phosphorylation of GRK2 increased its
      activity and binding to G betagamma. VIP-induced phosphorylation of VPAC(2)
      receptors was abolished in muscle cells expressing kinase-deficient GRK2(K220R)
      and attenuated in cells expressing GRK2(S685A) or by PKI. VPAC(2) receptor
      internalization (determined from residual (125)I-labeled VIP binding and receptor
      biotinylation after a 30-min exposure to VIP) was blocked in cells expressing
      GRK2(K220R) and attenuated in cells expressing GRK2(S685A) or by PKI. Finally,
      VPAC(2) receptor degradation (determined from residual (125)I-labeled VIP binding
      and receptor expression after a prolonged exposure to VIP) and functional VPAC(2)
      receptor desensitization (determined from the decrease in adenylyl cyclase
      activity and cAMP formation after a 30-min exposure to VIP) were abolished in
      cells expressing GRK2(K220R) and attenuated in cells expressing GRK2(S685A).
      These results demonstrate that in gastric smooth muscle VPAC(2) receptor
      phosphorylation is mediated by GRK2. Phosphorylation of GRK2 by PKA enhances GRK2
      activity and its ability to induce VPAC(2) receptor phosphorylation,
      internalization, desensitization, and degradation.

PMID- 18077608
TI  - Ischemic defects in the electron transport chain increase the production of
      reactive oxygen species from isolated rat heart mitochondria.
AB  - Cardiac ischemia decreases complex III activity, cytochrome c content, and
      respiration through cytochrome oxidase in subsarcolemmal mitochondria (SSM) and
      interfibrillar mitochondria (IFM). The reversible blockade of electron transport
      with amobarbital during ischemia protects mitochondrial respiration and decreases
      myocardial injury during reperfusion. These findings support that mitochondrial
      damage occurs during ischemia and contributes to myocardial injury during
      reperfusion. The current study addressed whether ischemic damage to the electron
      transport chain (ETC) increased the net production of reactive oxygen species
      (ROS) from mitochondria. SSM and IFM were isolated from 6-mo-old Fisher 344 rat
      hearts following 25 min global ischemia or following 40 min of perfusion alone as
      controls. H(2)O(2) release from SSM and IFM was measured using the amplex red
      assay. With glutamate as a complex I substrate, the net production of H(2)O(2)
      was increased by 178 +/- 14% and 179 +/- 17% in SSM and IFM (n = 9),
      respectively, following ischemia compared with controls (n = 8). With succinate
      as substrate in the presence of rotenone, H(2)O(2) increased by 272 +/- 22% and
      171 +/- 21% in SSM and IFM, respectively, after ischemia. Inhibitors of electron
      transport were used to assess maximal ROS production. Inhibition of complex I
      with rotenone increased H(2)O(2) production by 179 +/- 24% and 155 +/- 14% in SSM
      and IFM, respectively, following ischemia. Ischemia also increased the antimycin
      A-stimulated production of H(2)O(2) from complex III. Thus ischemic damage to the
      ETC increased both the capacity and the net production of H(2)O(2) from complex I
      and complex III and sets the stage for an increase in ROS production during
      reperfusion as a mechanism of cardiac injury.

PMID- 18077609
TI  - Diagnosing chlamydia and managing proctitis in men who have sex with men: current
      UK practice.
AB  - OBJECTIVES: This study was undertaken to ascertain clinic practices with respect
      to testing men who have sex with men (MSM) for chlamydial infection and the
      management of men with proctitis. METHODS: A cross-sectional survey of
      genitourinary medicine clinics in the United Kingdom undertaken in 2006. The
      questions concerned clinical practice regarding testing MSM for chlamydial
      infection at different anatomical sites, the clinical procedures used in the
      investigation of a MSM, the use of rectal smear microscopy, and the treatment
      used for rectal chlamydial infection. RESULTS: A nucleic acid amplification test
      was used for the diagnosis of chlamydial infection in the majority of clinics,
      although 12 (11%) were using methods that are no longer recommended (enzyme
      immunoassays). Testing for rectal chlamydial infection was undertaken in most
      clinics: 63 (60%) for screening in all MSM; 28 (27%) for diagnostic purposes or
      in contacts; 15 clinics did not offer any rectal testing. Anoscopy was offered to
      MSM in 99 clinics (93%), and rectal smear microscopy was undertaken in 76 clinics
      (71%). In 48 of the 76 clinics that undertook microscopy (64%), the number of
      cells in a defined microscopical field was counted; there was little consistency
      in what constituted proctitis. Only 58 clinics (58%) used treatment regimens
      recommended for lymphogranuloma venereum in men with symptomatic chlamydial
      proctitis. Testing for pharyngeal chlamydial infection was undertaken in 38
      clinics (36%). CONCLUSIONS: There is a wide variation in the diagnosis and
      management of chlamydial infection in MSM and there is an urgent need for a more
      consistent approach.

PMID- 18077610
TI  - Health economic methodology illustrated with recent work on Chlamydia screening:
      the concept of extended dominance.
AB  - The health economic concepts of dominance were reviewed on the basis of two
      recently published cost-effectiveness analyses on screening for asymptomatic
      Chlamydia trachomatis, one in this journal. On the basis of dominance, some
      strategies may be deleted from the set options from which to choose. The two
      investigated studies were from the United Kingdom and The Netherlands. Both
      studies nicely illustrate situations of so-called extended dominance in practical
      decision making. Extended dominance is a theoretical topic in many health
      economic text books but is only scarcely encountered in daily practice. Although
      the concept of extended dominance is theoretical in nature, a formal analysis and
      explanation may help show which options under consideration are not optimal from
      a strictly health-economic perspective; however, these options might still be
      attractive policy options for other reasons.

PMID- 18077611
TI  - A double-blind, randomized, controlled, multicenter safety and immunogenicity
      study of a refrigerator-stable formulation of Zostavax.
AB  - The vaccine Zostavax has been shown to prevent herpes zoster (HZ) and
      postherpetic neuralgia and is recommended for individuals > or =60 years of age.
      This study compared the safety and the immunogenicity of a refrigerator-stable
      formulation (Zostavax refrigerated) with those of the current formulation
      (Zostavax frozen) in subjects > or =50 years of age. Subjects with a negative
      history for HZ were randomized 1:1 to receive one dose of either formulation.
      Enrollment was stratified 1:2 by age (50 to 59 years and > or =60 years). Safety
      was evaluated for 28 days postvaccination. Varicella-zoster virus (VZV) antibody
      responses were measured by a glycoprotein enzyme-linked immunosorbent assay
      (gpELISA). The primary endpoints were the VZV antibody geometric mean titer (GMT;
      day 28), the VZV antibody geometric mean rise (GMR; days 1 to 28), and the
      incidence of vaccine-related serious adverse experiences (AEs) over 28 days. The
      refrigerated (n = 182) and frozen (n = 185) formulations induced similar GMTs
      (727.4 and 834.4 gpELISA units/ml, respectively); the estimated GMT ratio
      (refrigerated formulation/frozen formulation) was 0.87 (95% confidence interval,
      0.71 to 1.07). The GMRs were 2.6- and 2.9-fold, respectively. No vaccine-related
      serious AEs were reported in either group, and the safety profiles of the
      formulations were generally similar. The frequencies of injection-site AEs during
      follow-up were 35.6% and 46.4% in the refrigerated and the frozen formulation
      groups, respectively, and were generally mild. The frequencies of systemic AEs
      were similar in the two groups, and those of vaccine-related AEs were
      approximately 6% in both groups. The refrigerator-stable formulation of Zostavax
      has an acceptable safety profile and is as immunogenic as the frozen formulation;
      thus, the vaccine may be used in clinical settings where freezer availability is
      limited.

PMID- 18077612
TI  - Humoral immune responses of type 1 diabetes patients to Mycobacterium avium
      subsp. paratuberculosis lend support to the infectious trigger hypothesis.
AB  - Mycobacterium avium subsp. paratuberculosis is a zoonotic pathogen whose
      association with Crohn's disease in humans is under scrutiny. The objective of
      this work was to investigate its association with other chronic diseases such as
      type 1 diabetes mellitus (T1DM), where the involvement of a persistent pathogen
      such as M. avium subsp. paratuberculosis could be the trigger. For this purpose,
      59 diabetic patients and 59 healthy controls were investigated for the presence
      of antibodies against two recombinant proteins of M. avium subsp.
      paratuberculosis and the whole-cell lysate. Extremely significant humoral immune
      responses to recombinant heparin binding hemagglutinin and glycosyl transferase
      proteins and the whole-cell lysates of M. avium subsp. paratuberculosis bacilli
      were observed in T1DM patients and compared to those of healthy controls. Finding
      evidence of M. avium subsp. paratuberculosis involvement in T1DM is perhaps a
      novel finding that might serve as a foundation stone in establishing an
      infectious etiology for T1DM.

PMID- 18077613
TI  - Detection of Mycobacterium avium subsp. paratuberculosis by a sonicate
      immunoassay based on surface-enhanced Raman scattering.
AB  - A sandwich immunoassay for the rapid, low-level detection of Mycobacterium avium
      subsp. paratuberculosis has been developed. M. avium subsp. paratuberculosis is
      the causative agent of Johne's disease in cattle, and one of the major obstacles
      in controlling the spread of this disease is the inability to rapidly detect
      small amounts of bacteria or other diagnostic markers shed during the subclinical
      stage of infection. This paper details the development and performance of an
      assay for sonicated M. avium subsp. paratuberculosis lysate that is based on
      surface-enhanced Raman scattering (SERS). There are two key components of the
      assay: (i) an immobilized layer of monoclonal antibodies that target a surface
      protein on the microorganism; and (ii) extrinsic Raman labels (ERLs) that are
      designed to selectively bind to captured proteins and produce large SERS signals.
      By correlating the number of M. avium subsp. paratuberculosis bacilli present
      prior to sonication to the amount of total protein in the resulting sonicate, the
      detection limit determined for total protein can be translated to the
      microorganism concentration. These findings yield detection limits of 100 and 200
      ng/ml (estimated to be 500 and 1,000 M. avium subsp. paratuberculosis bacilli/ml)
      for sonicate spiked in phosphate buffer and sonicate spiked in whole milk,
      respectively. Moreover, the time required to complete the assay, which includes
      sample preparation, antigen extraction, ERL incubation, and readout, is less than
      24 h. The potential for incorporation of this novel assay into diagnostic
      laboratories is also briefly discussed.

PMID- 18077614
TI  - Performance characteristics of microparticle enzyme and chemiluminescence
      immunoassays for measurement of anti-HBc immunoglobulin M in sera of patients
      with HBeAg-negative chronic hepatitis B virus infection.
AB  - The IMx, AxSym, and Architect immunoglobulin M anti-HBc assay systems for
      detecting hepatitis B virus e antigen-negative chronic hepatitis B virus
      infection were compared. Despite good intra- and interassay coefficients of
      variation, significantly different values and low correlation (overestimation by
      AxSym and underestimation by Architect) were observed. Association and cutoff
      values for distinguishing patients with viral replication should be established
      for all methods.

PMID- 18077615
TI  - Impact of protein shedding on detection of Mycobacterium avium subsp.
      paratuberculosis by a whole-cell immunoassay incorporating surface-enhanced Raman
      scattering.
AB  - The etiological agent of Johne's disease is Mycobacterium avium subsp.
      paratuberculosis. Controlling the spread of this disease is hindered by the lack
      of sensitive, selective, and rapid detection methods for M. avium subsp.
      paratuberculosis. By using a recently optimized sandwich immunoassay (B. J.
      Yakes, R. J. Lipert, J. P. Bannantine, and M. D. Porter, Clin. Vaccine Immunol.
      15:227-234, 2008), which incorporates a new monoclonal antibody for the selective
      capture and labeling of M. avium subsp. paratuberculosis and surface-enhanced
      Raman scattering for sensitive readout, detection limits of approximately 630 and
      approximately 740 M. avium subsp. paratuberculosis cells/ml are achieved in
      phosphate-buffered saline and whole milk samples, respectively, after spiking
      with heat-treated M. avium subsp. paratuberculosis. Surprisingly, these detection
      limits are 3 orders of magnitude lower than expected based on theoretical
      predictions. Experiments designed to determine the origin of the improvement
      revealed that the major membrane protein targeted by the monoclonal antibody was
      present in the sample suspensions as shed protein. This finding indicates that
      the capture and labeling of shed protein function as a facile amplification
      strategy for lowering the limit of detection for M. avium subsp. paratuberculosis
      that may also be applicable to the design of a wide range of highly sensitive
      assays for other cells and viruses.

PMID- 18077616
TI  - Cryptococcal glucoxylomannan does not exhibit cross-reactivity in the MVista
      Histoplasma antigen enzyme immunoassay.
AB  - The potential for cross-reaction between Cryptococcus neoformans and Histoplasma
      capsulatum in antigen assays was evaluated. We tested patient samples, spleens
      from infected mice, and purified polysaccharides in the MVista Histoplasma
      antigen enzyme immunoassay and cryptococcal antigen latex agglutination system
      for cross-reactivity, and none was observed.

PMID- 18077617
TI  - Use of commercial enzyme immunoassays to detect antibodies to the herpes simplex
      virus type 2 glycoprotein G in a low-risk population in Hanoi, Vietnam.
AB  - Sera from 1,238 Vietnamese women in Hanoi were tested for herpes simplex virus
      type 2 (HSV-2). HSV-2 prevalence was 2.0%. The Kalon and Biokit assays showed
      significantly higher concordance to Western blotting data than did the Focus
      assay (P < 0.01). Screening by Focus and then retesting with Kalon/Biokit of
      positive samples can reduce falsely positive results significantly (P < 0.01).

PMID- 18077618
TI  - Implications of Streptococcus pneumoniae penicillin resistance and serotype
      distribution in Kuwait for disease treatment and prevention.
AB  - Streptococcus pneumoniae causes serious infections. Treatment is difficult
      because of the emergence of penicillin resistance in S. pneumoniae. Pneumococcal
      vaccines offer the promise of control and prevention of pneumococcal infections.
      Serotype prevalence and penicillin susceptibility data for a country will predict
      the usefulness of the vaccines in that country. In Kuwait, the 23-valent
      polysaccharide and the 7-valent conjugate vaccines are being used without
      knowledge of the prevalent serotypes in the country. To obtain the necessary
      background information, data on penicillin susceptibility and serogroups were
      obtained from 397 consecutive clinical isolates collected during 2004 and 2005.
      Two hundred fifty-three isolates (64%) were penicillin resistant, and resistance
      was significantly higher in patients < or =15 years old and among the upper
      respiratory tract and eye isolates. The most common serotypes were 23F, 19F, 6A,
      6B, 14, and 19A. Among the penicillin-resistant strains, the most common
      serotypes were 23F, 19F, 6B, 14, and 9A. Among the invasive strains, the most
      common serotypes were 14, 23F, 19A, and 9V. The polysaccharide vaccine gave 82%
      coverage against invasive infections in all age groups >2 years. The coverage of
      the 7-valent conjugate vaccine against invasive serotypes in children < or =2
      years old was 55%. This moderate coverage by the conjugate vaccine against
      invasive infections in children necessitates a revised strategy on the use of the
      present conjugate vaccine and shows the need for formulation of an improved
      vaccine for superior coverage for Kuwait and possibly other countries of the
      Arabian Gulf.

PMID- 18077619
TI  - Profiling antibodies to Mycobacterium tuberculosis by multiplex microbead
      suspension arrays for serodiagnosis of tuberculosis.
AB  - Tuberculosis (TB) is a serious global disease. The fatality rate attributed to TB
      is among the highest of infectious diseases, with approximately 2 million deaths
      occurring per year worldwide. Identification of individuals infected with
      Mycobacterium tuberculosis and screening of their immediate contacts is crucial
      for controlling the spread of TB. Current methods for detection of M.
      tuberculosis infection are not efficient, in particular, for testing large
      numbers of samples. We report a novel and efficient multiplex microbead
      immunoassay (MMIA), based on Luminex technology, for profiling antibodies to M.
      tuberculosis. Microbead sets identifiable by unique fluorescence were
      individually coated with each of several M. tuberculosis antigens and tested in
      multiplex format for antibody detection in the experimental nonhuman primate
      model of TB. Certain M. tuberculosis antigens, e.g., ESAT-6, CFP-10, and HspX,
      were included to enhance the specificity of the MMIA, because these antigens are
      absent in nontuberculous mycobacteria and the vaccine strain Mycobacterium bovis
      bacillus Calmette-Guerin. The MMIA enabled simultaneous detection of multiple M.
      tuberculosis plasma antibodies in several cohorts of macaques representing
      different stages of infection and/or disease. Antibody profiles were defined in
      early and latent/chronic infection. These proof-of-concept findings demonstrate
      the potential clinical use of the MMIA. In addition, the MMIA serodetection
      system has a potential for mining M. tuberculosis open reading frames (about
      4,000) to discover novel target proteins for the development of more
      comprehensive TB serodiagnostic tests.

PMID- 18077620
TI  - VirB12 is a serological marker of Brucella infection in experimental and natural
      hosts.
AB  - The Brucella species type IV secretion system, encoded by the virB1-12 locus, is
      required for intracellular replication and persistent infection in vivo. The
      requirement of VirB proteins for infection suggests that they are expressed in
      vivo and may therefore represent serological markers of infection. To test this
      idea, we purified recombinant VirB1, VirB5, VirB11, and VirB12 and tested for
      their recognition by antibodies in sera from experimentally infected mice and
      goats by using an indirect enzyme-linked immunosorbent assay. Antibody responses
      to VirB12 but not to VirB1, VirB5, or VirB11 were detected in 20/20 mice
      experimentally inoculated with Brucella abortus and 12/12 goats experimentally
      infected with Brucella melitensis. The potential use of VirB12 as a serological
      tool for the diagnosis of brucellosis was evaluated in the natural bovine host.
      Serum samples from 145 cattle of known serology (29% negative and 71% positive)
      were analyzed for the production of antibody responses to VirB12. One hundred two
      cattle samples (70.3%) were positive for antibodies to VirB12, while 43 samples
      were negative (29.7%). A positive serological response to VirB12 correlated with
      positive serology to whole B. abortus antigen in 99% of samples tested. These
      results show that VirB12 is expressed during infection of both experimental and
      natural hosts of Brucella species, and they suggest that VirB12 may be a useful
      serodiagnostic marker for brucellosis.

PMID- 18077621
TI  - Peptide impurities in commercial synthetic peptides and their implications for
      vaccine trial assessment.
AB  - The advent of T-cell assay methodologies that are amenable to high throughput
      coupled with the availability of large libraries of overlapping peptides have
      revolutionized the fields of vaccine efficacy testing and cellular immune
      response assessment. Since T-cell assay performance is critically dependent upon
      the quality and specificity of the stimulating peptides, assurance of high
      quality and reliable input peptides is an important aspect of assay validation.
      Herein, we demonstrate that individual peptides from large human immunodeficiency
      virus (HIV)-based peptide library sets obtained directly from two independent
      custom peptide suppliers contained contaminating peptides capable of giving false
      positive results, which were consistent with nominal antigen-specific CD8+ T-cell
      responses. In-depth investigation of the cellular response in terms of responding
      CD8+ T-cell frequency and human leukocyte antigen (HLA) restriction led to the
      conclusion that one set of HIV type 1 (HIV-1)-derived peptides was contaminated
      with a peptide from human cytomegalovirus (HCMV), which is commonly used in
      cellular immunology research applications. Analytical characterization of the
      original stock of the suspect HIV-1 peptide confirmed the presence of
      approximately 1% by weight of the HCMV peptide. These observations have critical
      implications for quality assurance (QA) and quality control (QC) of peptides used
      in clinical trials where cellular immune-based assays are important end-point
      determinants. We propose a simple schema of biological QA/QC protocols to augment
      the standard biochemical QA/QC analyses as a means to circumvent this and other
      problems that can affect cellular immune-based assay outcome and interpretation.

PMID- 18077622
TI  - Preparation of bacterial DNA template by boiling and effect of immunoglobulin G
      as an inhibitor in real-time PCR for serum samples from patients with
      brucellosis.
AB  - Real-time PCR is a widely used tool for the diagnosis of many infectious
      diseases. However, little information exists about the influences of the
      different factors involved in PCR on the amplification efficiency. The aim of
      this study was to analyze the effect of boiling as the DNA preparation method on
      the efficiency of the amplification process of real-time PCR for the diagnosis of
      human brucellosis with serum samples. Serum samples from 10 brucellosis patients
      were analyzed by a SYBR green I LightCycler-based real-time PCR and by using
      boiling to obtain the DNA. DNA prepared by boiling lysis of the bacteria isolated
      from serum did not prevent the presence of inhibitors, such as immunoglobulin G
      (IgG), which were extracted with the template DNA. To identify and confirm the
      presence of IgG, serum was precipitated to separate and concentrate the IgG and
      was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      Western blotting. The use of serum volumes above 0.6 ml completely inhibited the
      amplification process. The inhibitory effect of IgG in serum samples was not
      concentration dependent, and it could be eliminated by diluting the samples 1/10
      and 1/20 in water. Despite the lack of the complete elimination of the IgG from
      the template DNA, boiling does not require any special equipment and it provides
      a rapid, reproducible, and cost-effective method for the preparation of DNA from
      serum samples for the diagnosis of brucellosis.

PMID- 18077623
TI  - Activation of innate immunity in healthy Macaca mulatta macaques by a single
      subcutaneous dose of GMP CpG 7909: safety data and interferon-inducible protein
      10 kinetics for humans and macaques.
AB  - Following a demonstration that mouse-optimized cytosine-guanosine dinucleotide
      (CpG) oligodeoxynucleotides stimulated innate immune protection against
      intracellular pathogens, we tested the ability of CpG 7909, a primate-optimized
      Toll-like receptor 9 (TLR9) agonist, to stimulate rhesus macaques to produce
      interferon-inducible protein-10 (IP-10), a biomarker of immune activation. This
      study was performed prior to a similar trial with humans in order to facilitate
      the development of CpG 7909 as an immunomodulator for biodefense. A single
      subcutaneous dose of clinical-grade CpG 7909 was given to four groups of healthy
      adult rhesus macaques (0-mg dose [n = 5], 0.75-mg dose [n = 9], 1.5-mg dose [n =
      9], and 3.0-mg dose [n = 9]). Directed physical examination findings, clinical
      laboratory values, and serum IP-10 concentrations were collected at scheduled
      intervals for 28 days. All three dose levels of CpG 7909 were safe and not
      associated with significant clinical or laboratory abnormality. The time to peak
      serum IP-10 concentration was 1.0 days at the 0.75-mg dose and 0.5 days at the
      1.5- and 3.0-mg doses. A dose-dependent response was observed for the magnitude
      and duration of IP-10 concentrations, which remained significantly above baseline
      for 3 days for the 3.0-mg and 1.5-mg dose groups but above baseline for only 2
      days for the 0.75-mg dose group. There were no nonresponders to CpG 7909. These
      rhesus macaque safety and IP-10 response data closely parallel a subsequent phase
      1 human study of subcutaneously administered CpG 7909. A single dose of clinical
      grade CpG 7909 induced a rapid, sustained IP-10 response, a biomarker for
      activation of the innate immune system. Given the similar susceptibilities of
      humans and rhesus macaques to infectious diseases, the rhesus macaque appears to
      be a suitable model to evaluate the potential of CpG 7909-mediated innate immune
      activation to protect humans against pathogens.

PMID- 18077624
TI  - Cellular targeting of the apoptosis-inducing compound gliotoxin to fibrotic rat
      livers.
AB  - Liver fibrosis is associated with proliferation of hepatic stellate cells (HSCs)
      and their transformation into myofibroblastic cells that synthesize scar tissue.
      Several studies indicate that induction of apoptosis in myofibroblastic cells may
      prevent fibrogenesis. Gliotoxin (GTX) was found to induce apoptosis of hepatic
      cells and caused regression of liver fibrosis. However, the use of apoptosis
      inducing drugs may be limited due to lack of cell specificity, with a risk of
      severe adverse effects. In previous studies, we found that mannose-6-phosphate
      modified human serum albumin (M6P-HSA) selectively accumulated in liver
      fibrogenic cells. The aim of this study therefore was to couple GTX to M6P-HSA
      and test its pharmacological effects in vitro and in rats with liver fibrosis.
      The conjugate GTX-M6P-HSA bound specifically to HSCs and reduced their viability.
      Apoptosis was induced in cultures of human hepatic myofibroblasts (hMFs) and in
      liver slices obtained from rats with liver fibrosis. In vivo treatment with GTX
      or GTX-M6P-HSA in bile duct ligated rats revealed a significant decrease in alpha
      smooth muscle actin mRNA levels and a reduced staining for this HSC marker in
      fibrotic livers. In addition, although GTX also affected hepatocytes, GTX-M6P-HSA
      did not significantly affect other liver cells. In conclusion, we developed an
      HSC-specific compound that induced apoptosis in human hMFs, rat HSCs, and in
      fibrotic liver slices. In vivo, both GTX and GTX-M6P-HSA attenuated the number of
      activated HSCs, but GTX also affected hepatocytes. This study shows that cell
      selective delivery of the apoptosis-inducing agent GTX is feasible in fibrotic
      livers.

PMID- 18077625
TI  - Reduction of peroxisome proliferation-activated receptor gamma expression by
      gamma-irradiation as a mechanism contributing to inflammatory response in rat
      colon: modulation by the 5-aminosalicylic acid agonist.
AB  - Radiation-induced intestinal injuries, including inflammation and immune
      response, remain a limiting factor in the effectiveness of pelvic radiotherapy
      and in the patient's quality of life during and after treatment. Peroxisome
      proliferation-activated receptor (PPAR) agonists are now emerging as therapeutic
      drugs for various inflammatory diseases that are characterized by impaired PPAR
      expression. The purpose of this study was to investigate the profile of PPAR
      expression in rat colonic mucosa 3 and 7 days after abdominal gamma-irradiation
      (10 Gy). We tested whether irradiation-induced acute inflammatory response could
      be modulated pharmacologically with the antiinflammatory properties of 5
      aminosalicylic acid (5-ASA) (250 mg/kg/day), which is a PPAR activator.
      Irradiation drastically reduced mRNA and protein levels of PPARalpha and -gamma
      and of the heterodimer retinoid X receptor (RXR)alpha at 3 days postirradiation.
      5-ASA treatment normalized both PPARgamma and RXRalpha expression at 3 days
      postirradiation and PPARalpha at 7 days. By promoting PPAR expression and its
      nuclear translocation, 5-ASA interfered with the nuclear factor (NF)-kappaB
      pathway, both by reducing irradiation-induced NF-kappaB p65
      translocation/activation and increasing the expression of nuclear factor-kappaB
      inhibitor (IkappaB) mRNA and protein. Therefore, 5-ASA prevents irradiation
      induced inflammatory processes as well as expression of tumor necrosis factor
      alpha, monocyte chemotactic protein-1, inducible nitric-oxide synthase, and
      macrophage infiltration. In addition, 5-ASA restores the interferon gamma/signal
      transducer and activator of transcription (STAT)-1 and STAT-3 concentrations that
      were impaired at 3 and 7 days postirradiation and are correlated with suppressor
      of cytokine signaling-3 repression. Collectively, these results indicate that
      PPAR agonists may be effective in the prevention of inflammatory processes and
      immune responses during and after pelvic radiotherapy.

PMID- 18077626
TI  - Efficient identification of clinically relevant Candida yeast species by use of
      an assay combining panfungal loop-mediated isothermal DNA amplification with
      hybridization to species-specific oligonucleotide probes.
AB  - The occurrence of invasive mycoses has progressively increased in recent years.
      Yeasts of the genus Candida remain the leading etiologic agents of those
      infections. Early identification of opportunistic yeasts may contribute
      significantly to improved disease management and the selection of appropriate
      antifungal therapy. We developed a rapid and reliable molecular identification
      system for clinically relevant yeasts that makes use of nonspecific primers to
      amplify a region of the 26S rRNA gene, followed by reverse hybridization of the
      digoxigenin-labeled products to a panel of species-specific oligonucleotide
      probes arranged on a nylon membrane macroarray format. DNA amplification was
      achieved by the recently developed loop-mediated isothermal DNA amplification
      technology, a promising option for the development of improved laboratory
      diagnostic kits. The newly developed method was successful in distinguishing
      among the major clinically relevant yeasts associated with bloodstream infections
      by using simple, rapid, and cost-effective procedures and equipment.

PMID- 18077628
TI  - Comprehensive study of Corynebacterium freneyi strains and extended and emended
      description of Corynebacterium freneyi Renaud, Aubel, Riegel, Meugnier, and
      Bollet 2001.
AB  - In 2001, Corynebacterium freneyi was described as a new fermentative, alpha
      glucosidase-positive Corynebacterium species related to C. xerosis based on data
      from three strains. During a review of our extensive culture collection we
      encountered 18 additional C. freneyi strains and further characterized them in
      detail. Thirteen of the 18 strains were isolated from female genital tract
      specimens without any obvious disease association. Phenotypically, C. freneyi can
      be easily differentiated from C. xerosis by its distinct wrinkled colonies
      whereas nearly all other routinely applied phenotypic tests do not allow a
      unanimous separation of C. freneyi from C. xerosis. Restriction length
      polymorphism analysis using CfoI of the 16S-23S rRNA gene intragenic spacer
      definitively allows differentiation between the two species. Surprisingly,
      comparative 16S rRNA gene analysis does not discriminate between C. freneyi and
      C. xerosis because the designated type strain of C. freneyi is not the most
      representative strain for this species. The present report also includes detailed
      data on the antimicrobial susceptibility pattern of C. freneyi presented here for
      the first time. Based on the large number of additional C. freneyi strains from
      our culture collection, we provide an extended and emended species description of
      C. freneyi.

PMID- 18077627
TI  - Development of multiplex assay for rapid characterization of Mycobacterium
      tuberculosis.
AB  - We have developed a multiplex assay, based on multiplex ligation-dependent probe
      amplification (MLPA), that allows simultaneous detection of multiple drug
      resistance mutations and genotype-specific mutations at any location in the
      Mycobacterium tuberculosis genome. The assay was validated on a reference panel
      of well-characterized strains, and the results show that M. tuberculosis can be
      accurately characterized by our assay. Eighteen discriminatory markers
      identifying drug resistance (rpoB, katG, inhA, embB), members of the M.
      tuberculosis complex (16S rRNA, IS6110, TbD1), the principal genotypic group
      (katG, gyrA), and Haarlem and Beijing strains (ogt, mutT2, mutT4) were targeted.
      A sequence specificity of 100% was reached for 16 of the 18 selected genetic
      targets. In addition, a panel of 47 clinical M. tuberculosis isolates was tested
      by MLPA in order to determine the correlation between phenotypic drug resistance
      and MLPA and between spoligotyping and MLPA. Again, all mutations present in
      these isolates that were targeted by the 16 functional probes were identified.
      Resistance-associated mutations were detected by MLPA in 71% of the identified
      rifampin-resistant strains and in 80% of the phenotypically isoniazid-resistant
      strains. Furthermore, there was a perfect correlation between MLPA results and
      spoligotypes. When MLPA is used on confirmed M. tuberculosis clinical specimens,
      it can be a useful and informative instrument to aid in the detection of drug
      resistance, especially in laboratories where drug susceptibility testing is not
      common practice and where the rates of multidrug-resistant and extensively drug
      resistant tuberculosis are high. The flexibility and specificity of MLPA, along
      with the ability to simultaneously genotype and detect drug resistance mutations,
      make MLPA a promising tool for pathogen characterization.

PMID- 18077629
TI  - Molecular and phenotypic data supporting distinct species statuses for
      Scedosporium apiospermum and Pseudallescheria boydii and the proposed new species
      Scedosporium dehoogii.
AB  - Based on the morphological, physiologic, and molecular (beta-tubulin gene) study
      of 141 isolates of the Pseudallescheria boydii species complex (including several
      synonyms) and relatives, the new species Scedosporium dehoogii is proposed.
      Scedosporium apiospermum and P. boydii are considered two different species and
      the new name Scedosporium boydii is proposed for the anamorph of the latter
      species. A summary of the key morphological and physiological features for
      distinguishing the species of Pseudallescheria/Scedosporium is provided.

PMID- 18077630
TI  - Treatment with tigecycline of recurrent urosepsis caused by extended-spectrum
      beta-lactamase-producing Escherichia coli.
AB  - A 25-year-old female was admitted to our intensive care unit with septic shock
      and multiorgan failure caused by extended-spectrum beta-lactamase-producing
      Escherichia coli originating from the right renal pelvis. A 16-day course of
      treatment with meropenem reversed the septic condition, but the infection
      recurred thereafter. The patient recovered fully after therapy was changed to
      tigecycline.

PMID- 18077631
TI  - Differences in potential for selection of clindamycin-resistant mutants between
      inducible erm(A) and erm(C) Staphylococcus aureus genes.
AB  - In staphylococci, inducible macrolide-lincosamide-streptogramin B (MLS(B))
      resistance is conferred by the erm(C) or erm(A) gene. This phenotype is
      characterized by the erythromycin-clindamycin "D-zone" test. Although clindamycin
      appears active in vitro, exposure of MLS(B)-inducible Staphylococcus aureus to
      this antibiotic may result in the selection of clindamycin-resistant mutants,
      either in vitro or in vivo. We have compared the frequencies of mutation to
      clindamycin resistance for 28 isolates of S. aureus inducibly resistant to
      erythromycin and bearing the erm(C) (n = 18) or erm(A) (n = 10) gene. Seven
      isolates susceptible to erythromycin or bearing the msr(A) gene (efflux) were
      used as controls. The frequencies of mutation to clindamycin resistance for the
      erm(A) isolates (mean +/- standard deviation, 3.4 x 10(-8) +/- 2.4 x 10(-8)) were
      only slightly higher than those for the controls (1.1 x 10(-8) +/- 6.4 x 10(-9)).
      By contrast, erm(C) isolates displayed a mean frequency of mutation to
      clindamycin resistance (4.7 x 10(-7) +/- 5.5 x 10(-7)) 14-fold higher than that
      of the S. aureus isolates with erm(A). The difference was also observed, although
      to a lower extent, when erm(C) and erm(A) were cloned into S. aureus RN4220. We
      conclude that erm(C) and erm(A) have different genetic potentials for selection
      of clindamycin-resistant mutants. By the disk diffusion method, erm(C) and erm(A)
      isolates could be distinguished on the basis of high- and low-level resistance to
      oleandomycin, respectively.

PMID- 18077632
TI  - Bartonella tamiae sp. nov., a newly recognized pathogen isolated from three human
      patients from Thailand.
AB  - Three strains of a novel Bartonella species (Bartonella tamiae) were isolated
      from human patients from Thailand. Sequence analysis of six chromosomal regions
      (16S rRNA, gltA, groEL, ftsZ, rpoB, and the intergenic spacer region) and
      phenotypical analysis supported the similarity of the three strains and placed
      them within the genus Bartonella separately from previously described species.

PMID- 18077633
TI  - Candida krusei, a multidrug-resistant opportunistic fungal pathogen: geographic
      and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001
      to 2005.
AB  - Candida krusei is well known as a fungal pathogen for patients with hematologic
      malignancies and for transplant recipients. Using the ARTEMIS Antifungal
      Surveillance Program database, we describe geographic and temporal trends in the
      isolation of C. krusei from clinical specimens and the in vitro susceptibilities
      of 3,448 isolates to voriconazole as determined by CLSI (formerly NCCLS) disk
      diffusion testing. In addition, we report the in vitro susceptibilities of
      bloodstream infection isolates of C. krusei to amphotericin B (304 isolates),
      flucytosine (254 isolates), anidulafungin (121 isolates), caspofungin (300
      isolates), and micafungin (102 isolates) as determined by CLSI broth
      microdilution methods. Geographic differences in isolation were apparent; the
      highest frequency of isolation was seen for the Czech Republic (7.6%) and the
      lowest for Indonesia, South Korea, and Thailand (0 to 0.3%). Overall, 83% of
      isolates were susceptible to voriconazole, ranging from 74.8% in Latin America to
      92.3% in North America. C. krusei was most commonly isolated from hematology
      oncology services, where only 76.7% of isolates were susceptible to voriconazole.
      There was no evidence of increasing resistance of C. krusei to voriconazole from
      2001 to 2005. Decreased susceptibilities to amphotericin B (MIC at which 90% of
      isolates were inhibited [MIC(90)], 4 microg/ml) and flucytosine (MIC(90), 16
      microg/ml) were noted, whereas 100% of isolates were inhibited by < or =2
      microg/ml of anidulafungin (MIC(90), 0.06 microg/ml), micafungin (MIC(90), 0.12
      microg/ml) or caspofungin (MIC(90), 0.25 microg/ml). C. krusei is an uncommon but
      multidrug-resistant fungal pathogen. Among the systemically active antifungal
      agents, the echinocandins appear to be the most active against this important
      pathogen.

PMID- 18077634
TI  - Health care-associated endocarditis caused by Staphylococcus aureus with reduced
      susceptibility to vancomycin.
AB  - Infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus
      with reduced vancomycin susceptibility (SARV) has been reported worldwide. We
      report the successful treatment of a pediatric patient with SARV IE and
      characterization of the infecting strain. The MIC of vancomycin rose from 1.5 to
      2 microg/ml, and the SARV was confirmed by population analysis.

PMID- 18077635
TI  - Human parechovirus type 1, 3, 4, 5, and 6 detection in picornavirus cultures.
AB  - Picornavirus cultures that could not be typed in neutralization assays were
      analyzed by VP1 reverse transcription-PCR (RT-PCR) and a virus discovery tool
      (VIDISCA). Human parechoviruses (HPeVs) were frequently identified, among which
      were the uncommon isolates HPeV-4, HPeV-5, and HPeV-6. The HPeV-5 isolate could
      be amplified only by VIDISCA and not by VP1 RT-PCR.

PMID- 18077636
TI  - Genotypic characteristics of Staphylococcus aureus isolates from a multinational
      trial of complicated skin and skin structure infections.
AB  - The impact of bacterial genetic characteristics on the outcome of patients with
      Staphylococcus aureus infections is uncertain. This investigation evaluated
      potential associations between bacterial genotype and clinical outcome using
      isolates collected as part of an international phase 2 clinical trial (FAST II)
      evaluating telavancin for the treatment of complicated skin and skin structure
      infections (cSSSI). Ninety S. aureus isolates from microbiologically evaluable
      patients with cSSSI enrolled in the FAST II trial from 11 sites in the United
      States (56 isolates, or 62%) and 7 sites in South Africa (34 isolates, or 38%)
      were examined for staphylococcal cassette chromosome mec, agr, and the presence
      of 31 virulence genes and subjected to pulsed-field gel electrophoresis (PFGE).
      South African methicillin-susceptible S. aureus (MSSA) isolates were more likely
      to carry certain virulence genes, including sdrD (P = 0.01), sea (P < 0.01), and
      pvl (P = 0.01). All 44 (49%) methicillin-resistant S. aureus (MRSA) isolates were
      from the United States; 37 (84%) were strain USA 300 by PFGE. In the United
      States, MRSA isolates were more likely than MSSA isolates to carry genes for sdrC
      (P = 0.03), map/eap (P = 0.05), fnbB (P = 0.11), tst (P = 0.02), sea (P = 0.04),
      sed (P = 0.04), seg (P = 0.11), sej (P = 0.11), agr (P = 0.09), V8 (P = 0.06),
      sdrD, sdrE, eta, etb, and see (P < 0.01 for all). MRSA isolates were more often
      clonal than MSSA isolates by PFGE. Isolates from patients who were cured were
      significantly more likely to contain the pvl gene than isolates from patients
      that failed or had indeterminate outcomes (79/84 [94%] versus 3/6 [50%]; P =
      0.01). S. aureus strains from different geographic regions have different
      distributions of virulence genes.

PMID- 18077637
TI  - Panton-valentine leukocidin-positive Staphylococcus aureus and foreign travel.

PMID- 18077638
TI  - Evaluation of a multiplex PCR for identification of enteroaggregative Escherichia
      coli.

PMID- 18077639
TI  - Early infant human immunodeficiency virus type 1 detection suitable for resource
      limited settings with multiple circulating subtypes by use of nested three
      monoplex DNA PCR and dried blood spots.
AB  - The early detection of human immunodeficiency virus type 1 (HIV-1) infection in
      infants is complicated by the persistence of maternal antibodies and by diverse
      HIV-1 subtypes. We developed a nested, three-monoplex HIV-1 DNA PCR (N3M-PCR)
      assay to detect diverse HIV-1 subtypes in infants born to infected mothers. We
      optimized the test for use with dried blood spot (DBS) samples for ease of
      storage and transport from rural China to central laboratories. Six pairs of
      primers were designed that targeted env, gag, and pol genes, and the test was run
      in three reactions with an analytical sensitivity of 10 copies DNA per reaction
      to cover nine HIV-1 subtypes, A, B, C, D, F, G, CRF01-AE, CRF08-BC, and CRF07-BC.
      The assay performance was evaluated on 347 DBS specimens from 151 exposed infants
      in four diverse provinces of China in which multiple subtypes were circulating.
      The results of this test were compared to those of HIV antibody enzyme
      immunoassay and Western blotting confirmation for the infants at > or =18 months
      of age or to convincing clinical and epidemiologic data for deceased infants. The
      sensitivity of the N3M-PCR assay was 30.0% (3/10) for infants at 48 h after
      birth, 91.7% (11/12) at 1 to 2 months of age, and 93.7% (15/16) at 3 to 6 months
      of age. The specificity was 100% (94/94) at all three time points. The PCR
      reproducibility in the three DNA regions was 100% for samples at 48 h after
      birth, 96.7% at 1 to 2 months, and 100% at 3 to 6 months of age. The HIV-1 DNA
      N3M-PCR assay on DBSs offers a simple and affordable approach for early infant
      HIV-1 diagnosis in regions with diverse HIV-1 circulating subtypes.

PMID- 18077640
TI  - Multiprimer PCR system diagnosis of pulmonary tuberculosis in Cochabamba,
      Bolivia.

PMID- 18077641
TI  - Candida bracarensis detected among isolates of Candida glabrata by peptide
      nucleic acid fluorescence in situ hybridization: susceptibility data and
      documentation of presumed infection.
AB  - Molecular taxonomic studies have revealed new Candida species among
      phenotypically delineated species, the best example being Candida dubliniensis.
      This study was designed to determine the occurrence of two new molecularly
      defined species, Candida bracarensis and Candida nivariensis, which are closely
      related to and identified as Candida glabrata by phenotypic assays. A total of
      137 recent clinical isolates of C. glabrata identified by phenotypic
      characteristics was tested with C. bracarensis and C. nivariensis species
      specific peptide nucleic acid fluorescence in situ hybridization probes. Three of
      137 (2.2%) isolates were positive with the C. bracarensis probe, whereas the
      control strain, but none of the clinical isolates, was positive with the C.
      nivariensis probe. D1/D2 sequencing confirmed the identification of the three
      isolates as representing C. bracarensis. Clinically, one C. bracarensis isolate
      was recovered from a presumed infection, a polymicrobial pelvic abscess in a
      patient with perforated diverticulitis. The other two isolates were recovered
      from two adult oncology patients who were only colonized. C. bracarensis was
      white on CHROMagar Candida, had variable API-20C patterns that overlapped with C.
      nivariensis and some C. glabrata isolates, and had variable results with a rapid
      trehalose assay. Interestingly, an isolate from one of the colonized oncology
      patients was resistant to fluconazole, itraconazole, voriconazole, and
      posaconazole in vitro. In summary, C. bracarensis was detected among clinical
      isolates of C. glabrata, while C. nivariensis was not. One C. bracarensis isolate
      causing a presumed deep infection was recovered, and another isolate was azole
      resistant. Whether clinical laboratories should identify C. bracarensis will
      require more data.

PMID- 18077642
TI  - Identification of Brachyspira hyodysenteriae and other pathogenic Brachyspira
      species in chickens from laying flocks with diarrhea or reduced production or
      both.
AB  - Cecal samples from laying chickens from 25 farms with a history of decreased egg
      production, diarrhea, and/or increased feed conversion ratios were examined for
      anaerobic intestinal spirochetes of the genus Brachyspira. Seventy-three samples
      positive in an immunofluorescence assay for Brachyspira species were further
      examined using selective anaerobic culture, followed by phenotypic analysis,
      species-specific PCRs (for Brachyspira hyodysenteriae, B. intermedia, and B.
      pilosicoli), and a Brachyspira genus-specific PCR with sequencing of the partial
      16S rRNA gene products. Brachyspira cultures were obtained from all samples. Less
      than half of the isolates could be identified to the species level on the basis
      of their biochemical phenotypes, while all but four isolates (5.2%) were
      speciated by using PCR and sequencing of DNA extracted from the bacteria.
      Different Brachyspira spp. were found within a single flock and also in cultures
      from single chickens, emphasizing the need to obtain multiple samples when
      investigating outbreaks of avian intestinal spirochetosis. The most commonly
      detected spirochetes were the pathogenic species B. intermedia and B. pilosicoli.
      The presumed nonpathogenic species B. innocens, B. murdochii, and the proposed
      "B. pulli" also were identified. Pathogenic B. alvinipulli was present in two
      flocks, and this is the first confirmed report of B. alvinipulli in chickens
      outside the United States. Brachyspira hyodysenteriae, the agent of swine
      dysentery, also was identified in samples from three flocks. This is the first
      confirmed report of natural infection of chickens with B. hyodysenteriae.
      Experimental infection studies are required to assess the pathogenic potential of
      these B. hyodysenteriae isolates.

PMID- 18077643
TI  - Pathotypical characterization and molecular epidemiology of Newcastle disease
      virus isolates from different hosts in China from 1996 to 2005.
AB  - Thirty Newcastle disease virus (NDV) strains isolated from outbreaks in China
      during 1996 to 2005 were characterized pathotypically and genotypically. All
      strains except one were velogenic. An analysis of the variable region
      (nucleotides 47 to 420) of the F gene indicated that 6 isolates belonged to
      genotype II, 3 to genotype III, 1 (isolated from a pigeon) to genotype VI, and 20
      to genotype VII. Isolates belonging to genotype VII were further divided into
      five subtypes, VIIa, VIIb, VIIc, VIId, and VIIe, and subtype VIId was made up of
      VIId1 to VIId5. These results showed that genotype VII isolates might have been
      the most prevalent in China during the past two decades. Genotype VII isolates
      shared high homology, but the homology was less than that between genotype VII
      viruses and the vaccine virus LaSota. Among these NDV isolates, 25 isolates had
      the velogenic motif (112)R/K-R-Q-K/R-R-F(117) that is consistent with results of
      the biological tests. However, four of five LaSota-type isolates that contained
      the lentogenic motif (112)G-R-Q-G-R-L(117) were velogenic, except SY/03, in the
      view of the biological test. The majority of genotype VII isolates had lost one
      or two N-glycosylation sites. Finally, a cross-protection experiment in which
      specific-pathogen-free chickens vaccinated with LaSota were challenged by six NDV
      isolates showed that more than three isolates were antigenic variants that could
      be responsible for recent outbreaks of Newcastle disease.

PMID- 18077644
TI  - Cervical human papillomavirus (HPV) infection and HPV type 16 antibodies in South
      African women.
AB  - There is a high incidence of cervical cancer in South African women. No large
      studies to assess human papillomavirus virus (HPV) infection or HPV type 16 (HPV
      16) exposure have occurred in the region, a requirement for policy making with
      regards to HPV screening and the introduction of vaccines. Control women (n =
      1,003) enrolled in a case control study of hormonal contraceptives and cervical
      cancer were tested for 27 cervical HPV types by reverse line blot analysis. The
      seroprevalence of HPV-16 immunoglobulin G (IgG) and IgA antibodies was assessed
      by a virus-like particle-based enzyme-linked immunoassay of 908 and 904 control
      women, respectively, and of 474 women with cervical cancer. The cervical HPV
      prevalence was 26.1%. The HPV-16 IgG seroprevalence was 44.4% and the HPV-16 IgA
      seroprevalence was 28.7% in control women, and these levels were significantly
      higher (61.8% and 52.7%, respectively) for women with cervical cancer (odds ratio
      [OR], 2.1 and 2.8, respectively). The cervical HPV prevalence showed an
      association with cervical disease, and the HPV-16 IgG prevalence decreased while
      the HPV-16 IgA prevalence increased with increasing age (P < 0.05). The
      prevalence of oncogenic HPV types (including HPV-16) decreased with age, whereas
      nononcogenic HPV types showed limited association with age. Multivariate analysis
      revealed cervical HPV infection to be associated with herpes simplex virus type 2
      infection (OR, 1.7) and increasing years of education (OR, 1.9). HPV-16 IgG
      antibodies were inversely associated with current smoking status (OR, 0.6), and
      the presence of HPV-16 IgA antibodies was inversely associated with the use of
      alcohol (OR, 2.1) and inversely associated with the use of oral contraceptives
      (OR, 0.6). High levels of exposure to HPV, and particularly HPV-16, were evident
      in this population. The apparent increase of serum HPV-16 IgA with increasing age
      requires further investigation.

PMID- 18077645
TI  - Heterogeneity of hemolysin expression during neonatal Streptococcus agalactiae
      sepsis.
AB  - The beta-hemolysin of Streptococcus agalactiae is a major virulence factor;
      consequently, nonhemolytic strains rarely cause infections. We report on a case
      of neonatal sepsis caused by a strain displaying heterogeneous hemolysin
      expression. It was detected by the simultaneous isolation of hemolytic and
      nonhemolytic colonies from cultures of the infant's blood.

PMID- 18077646
TI  - Analysis of echovirus 30 isolates from Russia and new independent states
      revealing frequent recombination and reemergence of ancient lineages.
AB  - We studied two genome regions, VP1 and 3D, of 48 echovirus 30 (E30) isolates from
      Russia and the new independent states. In VP1, most isolates were similar to
      European strains reported earlier, and frequent change of circulating subgroups
      was noticed. We also observed, in 2003-2006, the reemergence of a group of E30
      strains with a VP1 region very distant from most modern E30 strains and remotely
      similar to E30 isolates from the 1960s and the 1970s. A study of the 3D genome
      region detected multiple recombination events among the studied strains.
      Recombination presumably occurred every few years, and therefore, the study of a
      single VP1 genome region cannot accurately describe the phylogenetic history of
      the virus or predict pathogenetic properties of an isolate. In general, a
      comparison of the VP1 and 3D genome region phylogenies revealed, in some
      instances, virtually independent circulation of enterovirus genome fragments on a
      scale of years.

PMID- 18077647
TI  - Evaluation of quantitative analysis of cultures from sonicated retrieved
      orthopedic implants in diagnosis of orthopedic infection.
AB  - To improve the microbiological diagnosis of device-related osteoarticular
      infections, we have developed a protocol based on the sonication of device
      samples, followed by concentration and inoculation of the sonicate in a broad
      variety of media in a quantitative manner. Sixty-six samples from 31 patients
      were included in the study (17 of them with clinical diagnosis of infection). The
      sonication procedure had a sensitivity of 94.1%, which is better than that of
      conventional cultures (88.2%). One case of contamination and six cases of
      unexpected positive cultures were detected (specificity of 42.8%): two of these
      were considered to represent true infection, while the other four were considered
      to be nonsignificant (corrected specificity of 50%), although the clinical
      importance of these isolates is questionable. When we analyzed the number of CFU,
      no breakpoint between significant and nonsignificant isolates could be
      established. Based on our results, the procedure of sonication of retrieved
      implants is better than conventional cultures for the diagnosis of device-related
      infections. The significance of some isolates in patients without clinical
      infection remains uncertain. However, they may become pathogens and cannot be
      routinely considered to be contamination.

PMID- 18077648
TI  - Pulsed-field gel electrophoresis of Staphylococcus aureus isolates from atopic
      patients revealing presence of similar strains in isolates from children and
      their parents.
AB  - Skin colonization with Staphylococcus aureus is often associated with atopic
      dermatitis, and staphylococcal enterotoxins have been implicated in the etiology
      of atopic disease. In this study, the colonization of patients with atopic
      dermatitis and their parents was investigated in order to evaluate the
      possibility of intrafamiliar transmission. S. aureus strains were isolated from
      30 of 45 patients (66%). In 19 of 29 families (65%), at least one parent carried
      S. aureus, and the overall colonization rate of the parents was 48%. All strains
      were typed by pulsed-field gel electrophoresis (PFGE), and the presence of
      enterotoxin genes in the strains was assayed by multiplex PCR. A high percentage
      (84%) of the isolates present on the children and on at least one of their
      parents displayed identical PFGE and enterotoxin patterns as well as identical
      antibiotic resistance profiles, indicating intrafamiliar transmission. Forty-five
      percent of the strains did not carry any enterotoxin gene. The most frequently
      found enterotoxin genes were seg and sei, which were present in 36% of the
      strains, and seb, which was found in 24% of the strains. The other toxin genes
      occurred only in low frequencies. Most strains were resistant to penicillin
      (82%), and 15% showed resistance to more than one antibiotic. Intermediately
      vancomycin-resistant S. aureus or methicillin-resistant S. aureus strains were
      not detected. In conclusion, this study indicates that the colonization rate of
      parents of atopic children is rather high and may increase the risk of
      recolonization of the child.

PMID- 18077649
TI  - Prevalence and characterization of multidrug-resistant (type ACSSuT) Salmonella
      enterica serovar Typhimurium strains in isolates from four gosling farms and a
      hatchery farm.
AB  - Salmonella enterica serovar Typhimurium strains of phage types DT104 and U302 are
      often resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides, and
      tetracycline (the ACSSuT resistance type) and are major zoonotic pathogens.
      Increased consumption of goose meat may enhance the risk of transferring S.
      enterica serovar Typhimurium and other enteric pathogens from geese to human due
      to the consumption of meats from infected geese or improper preparation of meats.
      Therefore, we characterized S. enterica serovar Typhimurium strains isolated from
      four goose farms (farms A, B, C, and D) and one hatchery farm (farm E) to
      determine the epidemic and genetic differences among them. Antibiotic
      susceptibility tests and multiplex PCR confirmed that 77.6% (52/67) of strains
      were ACSSuT strains isolated from farms A, C, and E. Antibiotic-susceptible
      strains were isolated mostly from farm B, and no strain was observed in farm D.
      All ACSSuT strains harbored a 94.7-kb virulence plasmid and contained one 1.1-kb
      conserved segment identical to that of Salmonella genomic island 1. Four
      genotypes were determined among these S. enterica serovar Typhimurium isolates by
      pulsed-field gel electrophoresis analysis of XbaI-digested DNA fragments. Most
      isolates (85.29%; 29/34) of major genotype Ib were ACSSuT strains isolated mainly
      from goslings of farm C and egg membranes of farm E, a hatchery farm, suggesting
      that S. enterica serovar Typhimurium strains in isolates from goslings might
      originate from its hatchery, from the egg membranes to the gosling fluff after
      hatching. Multiple phage types, types 8, 12, U283, DT104, and U302, were
      identified. In conclusion, geese were a reservoir of diverse multidrug-resistant
      (type ACSSuT) S. enterica serovar Typhimurium strains, and each farm was
      colonized with genetically closely related S. enterica serovar Typhimurium
      strains.

PMID- 18077650
TI  - High-level fluoroquinolone resistance in ophthalmic clinical isolates belonging
      to the species Corynebacterium macginleyi.
AB  - The clinical importance of nondiphtherial Corynebacterium, a ubiquitous member of
      the normal human microflora of the skin and mucous membrane, for ocular surface
      infections has been recognized recently. We performed an antimicrobial
      susceptibility test with Etest strips for three fluoroquinolones (ciprofloxacin,
      norfloxacin, and levofloxacin) and a taxonomic analysis on 21 isolates of
      Corynebacterium from ophthalmic samples. Of these, 16 isolates were identified as
      C. macginleyi at the species level on the basis of 16S rRNA gene sequence
      comparisons. The remaining five isolates were determined to be C. mastitidis
      (four) or C. accolens (one). Eleven of the C. macginleyi isolates showed high
      levels of resistance to all of the fluoroquinolones tested, and one isolate was
      resistant to norfloxacin alone. An analysis of the amplified quinolone-resistance
      determining regions of the gyrA genes revealed that a single amino acid
      substitution in position 83 of the gyrA product was sufficient to generate the
      norfloxacin resistance phenotype, and double mutations leading to amino acid
      changes in positions 83 and 87 were necessary for high-level resistance against
      the other fluoroquinolones. We conducted the first example of multilocus sequence
      typing (MLST) analysis on C. macginleyi. The MLST analysis grouped the majority
      of C. macginleyi isolates into a single lineage, and another molecular strain
      typing by random amplified polymorphic DNA fragment patterns supported the
      finding, indicating that a particular lineage of C. macginleyi is dominant on the
      human ocular surface. This type of population might be particularly adaptable to
      the milieu on the human ocular surface.

PMID- 18077651
TI  - Prevalence and genetic diversity of hepatitis B and delta viruses in pregnant
      women in Gabon: molecular evidence that hepatitis delta virus clade 8 originates
      from and is endemic in central Africa.
AB  - Hepatitis B virus (HBV) surface antigen (HBsAg) was found in 9.2% of 1,186
      pregnant women from Gabon, of whom 10.1% had the HBe antigen and 89.9% had anti
      HBe antibodies. Antibodies to the hepatitis delta virus (HDV) were found in 15.6%
      of the HBsAg-positive women. The HBV strains were of the A3 and E genotypes. The
      HDV strains belonged to HDV clades 1 and 8. These results provide clear evidence
      that HDV clade 8 is indigenous to Africa.

PMID- 18077652
TI  - Discrimination of herpes simplex virus type 2 strains by nucleotide sequence
      variations.
AB  - We determined the polymorphous 400-bp regions in UL53, US1, and US4 for the
      discrimination of herpes simplex virus type 2 (HSV-2) strains. Thirty-six HSV-2
      clinical strains could be differentiated into 35 groups using these three regions
      and into 36 groups by additional analysis of three noncoding regions previously
      reported as polymorphous.

PMID- 18077653
TI  - A cervical cancer community-based participatory research project in a Native
      American community.
AB  - The Messengers for Health on the Apsaalooke Reservation project uses a community
      based participatory research (CBPR) approach and lay health advisors (LHAs) to
      generate knowledge and awareness about cervical cancer prevention among community
      members in a culturally competent manner. Northern Plains Native Americans, of
      whom Apsaalooke women are a part, continue to be disproportionately affected by
      cervical cancer. This article examines quantitative and qualitative changes that
      occurred in the community since the inception of the Messengers for Health
      program. Paired sample t tests are used to evaluate the one-group pretest and
      posttest interviews of 83 Apsaalooke women in knowledge, comfort, and cancer
      awareness levels. Results reveal cervical cancer knowledge gains, gains in
      participants' comfort discussing cancer issues, and gains in awareness of
      cervical cancer and the Messengers program. Field notes, meeting minutes, and
      community perceptions are used to qualitatively evaluate the effectiveness of the
      Messengers program. Practice implications are discussed.

PMID- 18077654
TI  - Self-efficacy mediates the relationship between depressive symptoms and
      medication adherence among hypertensive African Americans.
AB  - Many studies have documented the negative effects of depression on adherence to
      recommended treatment; however, little is known about the mechanism underlying
      this relationship. Using the Kenny and Baron analytic framework of mediation, the
      authors assessed whether self-efficacy mediated the relationship between
      depression and medication adherence in 167 hypertensive African Americans
      followed in a primary care practice. Depressive symptoms are associated with poor
      medication adherence (beta=.013, p=.036) and low self-efficacy (beta=-.008,
      p=.023). Self-efficacy is negatively associated with medication adherence at
      follow-up (beta=-.612, p<.001). The relationship between depressive symptoms and
      medication adherence becomes nonsignificant when controlling for self-efficacy
      (beta=.010, p=.087). Implications for further examination into the mediating role
      of self-efficacy and the deleterious effect of depression on medication adherence
      are discussed.

PMID- 18077655
TI  - Public health campaigns to change industry practices that damage health: an
      analysis of 12 case studies.
AB  - Industry practices such as advertising, production of unsafe products, and
      efforts to defeat health legislation play a major role in current patterns of
      U.S. ill health. Changing these practices may be a promising strategy to promote
      health. The authors analyze 12 campaigns designed to modify the health-related
      practices of U.S. corporations in the alcohol, automobile, food and beverage,
      firearms, pharmaceutical, and tobacco industries. The objectives are to examine
      the interactions between advocacy campaigns and industry opponents; explore the
      roles of government, researchers, and media; and identify characteristics of
      campaigns that are effective in changing health-damaging practices. The authors
      compared campaigns that operate at different levels of organization and use
      different strategies. Findings suggest that many campaigns achieve policy or
      mobilization outcomes that may contribute to improved health; local campaigns may
      be more effective than national ones; and advocates frequently frame their
      campaigns on the themes of children's health and social justice.

PMID- 18077656
TI  - Implementation of possession laws and the social ecology of tobacco control.
AB  - The objective of this evaluation research was to assess the impact of programs
      intended to support the enforcement component of a comprehensive youth tobacco
      control. The research method was a survey of a randomly stratified cluster sample
      of law enforcement officers. Results of the evaluation showed that the
      enforcement behaviors of officers were increased through the state programs to
      support tobacco enforcement activities. The study showed that support for
      implementing a policy is important to achieve the objectives of a policy. The
      results of a study of the enforcement component of a Florida tobacco control
      program are reported and discussed within the ecological context of previously
      reported enforcement-linked decreases in youth tobacco use and funding and
      defunding of the Florida Tobacco Control Program.

PMID- 18077657
TI  - Evaluating psychosocial and behavioral mechanisms of change in a tailored
      communication intervention.
AB  - This study examined the impact of a tailored nutrition intervention at 3 and 6
      months postintervention. In all, 357 Latinas were randomly assigned to one of
      three conditions: (1) a control condition comprised of previously developed
      Spanish language targeted materials, (2) tailored print materials, or (3)
      tailored print materials accompanied by personalized dietary counseling via lay
      heath advisors (promotoras). At 6 months postintervention, significant group by
      time interactions were observed on the dietary behavioral strategies scales. The
      promotora condition resulted in significant behavior change initially; however,
      receipt of tailored and control materials was instrumental in continued behavior
      change after intervention activities had ceased. Group main effects suggested
      that the promotora condition was superior at reducing barriers and improving
      family interactions supporting healthy behaviors. The promotora model is an
      effective method for changing important dietary behaviors and psychosocial
      determinants, but longer term behavior change is achievable with less expensive
      intervention methods.

PMID- 18077658
TI  - Identifying belief-based targets for the promotion of leisure-time walking.
AB  - Walking is the most common type of physical activity (PA) and the likely target
      of efforts to increase PA. No studies, however, have identified the belief-level
      correlates for walking using the theory of planned behavior. This study elicits
      salient beliefs about walking and evaluates beliefs that may be most important
      for walking-promotion campaigns. A random sample of 55 Canadian adults
      participated in the elicitation study, and the validation study includes 358
      participants who completed measures of demographics, beliefs from the elicitation
      study, and self-reported walking behavior. Belief-behavior relationships show
      that almost all behavioral expectancies are correlates of intention and behavior,
      but normative and control expectancies are more select correlates. But when
      belief-behavior relations are evaluated by participants meeting PA
      recommendations, only beliefs about feeling good, appearance, stress relief, and
      time are significant. Public health efforts to promote walking should focus on
      making time for regular walking and the affective advantages that walking can
      provide.

PMID- 18077659
TI  - Handedness leads to interhemispheric EEG asymmetry during sleep in the rat.
AB  - Sleep electroencephalographic (EEG) slow-wave activity is increased after
      wakefulness and decreases during sleep. Regional sleep EEG differences are
      thought to be a consequence of activation of specific cortical neuronal circuits
      during waking. We investigated the relationship between handedness and
      interhemispheric brain asymmetry. Bilateral EEG recordings were obtained from the
      frontal and occipital cortex in rats with a clear paw preference in a food
      reaching task (right, n = 5; left, n = 5). While still naive to the task, no
      waking or sleep EEG asymmetry was present. During the food-reaching task, the
      waking EEG showed significant, substantial power increases in the frontal
      hemisphere contralateral to the dominant paw in the low theta range (4.5-6.0 Hz).
      Moreover, the non-REM sleep EEG following feeding bouts was markedly asymmetric,
      with significantly higher power in the hemisphere contralateral to the preferred
      paw in frequencies >1.5 Hz. No asymmetry was evident in the occipital EEG.
      Correlation analyses revealed a positive association between the hemispheric
      asymmetry during sleep and the degree of preferred use of the contralateral paw
      during waking in frequencies <9.0 Hz. Our findings show that handedness is
      reflected in specific, regional EEG asymmetry during sleep. Neuronal activity
      induced by preferential use of a particular forelimb led to a local enhancement
      of EEG power in frequencies within the delta and sigma ranges, supporting the
      hypothesis of use-dependent local sleep regulation. We conclude that inherent
      laterality is manifested when animals are exposed to complex behavioral tasks,
      and sleep plays a role in consolidating the hemispheric dominance of the brain.

PMID- 18077660
TI  - Differential effects of corticosterone on the slow afterhyperpolarization in the
      basolateral amygdala and CA1 region: possible role of calcium channel subunits.
AB  - The stress hormone corticosterone increases the amplitude of the slow
      afterhyperpolarization (sAHP) in CA1 pyramidal neurons, without affecting resting
      membrane potential, input resistance, or action potential characteristics. We
      here examined how corticosterone affects these properties in the basolateral
      amygdala (BLA). In the amygdala, corticosterone does not change the AHP
      amplitude, nor any of the passive and active membrane properties studied. The
      lack of effect on the AHP is surprising since in both areas corticosterone
      increases high-voltage-activated sustained calcium currents, which supposedly
      regulate the sAHP. We wondered whether corticosterone targets different calcium
      channel subunits in the two areas because currents through only one of the
      subunits (Cav1.3) are thought to alter the AHP amplitude. In situ hybridization
      studies revealed that CA1 cells express Cav1.2 and Cav1.3 subunits;
      corticosterone does not transcriptionally regulate Cav1.2 but increases Cav1.3
      expression compared with vehicle treatment. In the BLA, Cav1.3 expression was not
      detectable, both after control and corticosterone treatment. Cav1.2 is moderately
      expressed. In a modeling study, we examined putative consequences of changes in
      specific calcium channel subunit expression and calcium extrusion by
      corticosterone for the AHP in CA1 and amygdala neurons. A differential
      distribution and transcriptional regulation of Cav1.2 and Cav1.3 in the CA1 area
      versus BLA partly explain the observed differences in AHP amplitude. The
      functional implication of these findings could be that stress-induced arousal of
      activity in the BLA is more prolonged than that in the CA1 hippocampal area, so
      that information with an emotional component is more effectively encoded.

PMID- 18077661
TI  - Homer 1a suppresses neocortex long-term depression in a cortical layer-specific
      manner.
AB  - Homer1a/Vesl-1S is an activity-dependently induced member of the scaffold protein
      family Homer/Vesl, which is known to link group I metabotropic glutamate
      receptors (mGluRs) to endoplasmic calcium release channels and to regulate them.
      Here we studied roles of Homer 1a in inducing long-term depression (LTD) in rat
      visual cortex slices. Homer 1a protein was injected by diffusion from whole cell
      patch pipettes. In layer VI pyramidal cells, LTD was reduced in magnitude with
      Homer 1a. LTD in layer VI was suppressed by applying antagonists of mGluR5, a
      subtype of group I mGluRs expressed with higher density than mGluR1 in neocortex
      pyramidal cells, or inositol-1,4,5-triphosphate receptors (IP3Rs) but not that
      against N-methyl-d-aspartate receptors (NMDARs). In layer II/III or layer V,
      Homer 1a injection was unable to affect LTD, which is mostly dependent on NMDARs
      and not on group I mGluRs in these layers. To examine the effects of endogenous
      Homer 1a, electroconvulsive shock (ECS) was applied. Homer 1a thereby induced, as
      did Homer 1a injection, reduced LTD magnitude in layer VI pyramidal cells and
      failed to do so in layer II/III or layer V pyramidal cells. These results
      indicate that both exo- and endogenous Homer 1a suppressed LTD in a cortical
      layer-specific manner, and its layer-specificity may be explained by the high
      affinity of Homer 1a to group I mGluRs.

PMID- 18077662
TI  - Responses to tactile stimulation in deep cerebellar nucleus neurons result from
      recurrent activation in multiple pathways.
AB  - In a previous study, we found that neurons in the deep cerebellar nuclei (DCN)
      respond to 5-ms brief facial tactile stimulation in rats anesthetized with
      ketamine-xylazine with multiphasic response patterns lasting over 200 ms. It
      remained unclear, however, to what extent these responses were shaped not only by
      ascending sensory input from the trigeminal nuclei but also by interactions with
      other major cerebellar afferent systems, in particular the inferior olive (IO)
      and cerebral cortex. In the present study, we recorded from the IO, cerebral
      cortex, cerebellar granule cell layer (GCL), and DCN during the presentation of 5
      ms facial tactile stimuli to elucidate potential mechanisms of how extended DCN
      response patterns are generated. We found that tactile stimulation resulted in
      robust multiphasic local field potentials responses in the IO as well as in the
      activation of a wide region of the somatosensory cortex (SI) and the primary
      motor cortex (MI). DCN neurons responded to electrical stimulation of any of
      these structures (IO, SI, and MI) with complex temporal patterns strikingly
      similar to air-puff lip stimulation responses. Simultaneous recordings from
      multiple structures revealed that long-lasting activation patterns elicited in
      DCN neurons were based on recurrent network activation in particular between the
      IO and the DCN with a potential contribution of DCN rebound properties. These
      results are consistent with the hypothesis that sensory stimulation triggers a
      feedback network activation of cerebellum, IO, and cerebral cortex to generate
      temporal patterns of activity that may control the timing of behavior.

PMID- 18077663
TI  - Testing basal ganglia motor functions through reversible inactivations in the
      posterior internal globus pallidus.
AB  - To test current hypotheses on the contribution of the basal ganglia (BG) to motor
      control, we examined the effects of muscimol-induced inactivations in the
      skeletomotor region of the internal globus pallidus (sGPi) on visually directed
      reaching. Injections were made in two monkeys trained to perform four out-and
      back reaching movements in quick succession toward four randomly selected target
      locations. Following sGPi inactivations the following occurred. 1) Peak velocity
      and acceleration were decreased in nearly all sessions, whereas movement duration
      lengthened inconsistently. 2) Reaction times were unaffected on average, although
      minor changes were observed in several individual sessions. 3) Outward reaches
      showed a substantial hypometria that correlated closely with bradykinesia, but
      directional accuracy was unaffected. 4) Endpoint accuracy was preserved for the
      slow visually guided return movements. 5) No impairments were found in the rapid
      chaining of out-and-back movements, in the selection or initiation of four
      independent reaches in quick succession or in the quick on-line correction of
      initially misdirected reaches. 6) Inactivation-induced reductions in the
      magnitude of movement-related muscle activity (EMG) correlated with the severity
      of slowing and hypometria. There was no evidence for inactivation-induced
      alterations in the relative timing of EMG bursts, excessive cocontraction, or
      impaired suppression of antagonist EMG. Therefore disconnecting the BG motor
      pathway consistently produced bradykinesia and hypometria, but seldom affected
      movement initiation time, feedback-mediated guidance, the capacity to produce
      iterative reaches, or the ability to abruptly reverse movement direction. These
      results are discussed with reference to the idea that the BG motor loop may
      regulate energetic expenditures during movement (i.e., movement "vigor").

PMID- 18077664
TI  - Circadian- and light-dependent regulation of resting membrane potential and
      spontaneous action potential firing of Drosophila circadian pacemaker neurons.
AB  - The ventral lateral neurons (LNvs) of adult Drosophila brain express oscillating
      clock proteins and regulate circadian behavior. Whole cell current-clamp
      recordings of large LNvs in freshly dissected Drosophila whole brain preparations
      reveal two spontaneous activity patterns that correlate with two underlying
      patterns of oscillating membrane potential: tonic and burst firing of sodium
      dependent action potentials. Resting membrane potential and spontaneous action
      potential firing are rapidly and reversibly regulated by acute changes in light
      intensity. The LNv electrophysiological light response is attenuated, but not
      abolished, in cry(b) mutant flies hypomorphic for the cell-autonomous light
      sensing protein CRYPTOCHROME. The electrical activity of the large LNv is
      circadian regulated, as shown by significantly higher resting membrane potential
      and frequency of spontaneous action potential firing rate and burst firing
      pattern during circadian subjective day relative to subjective night. The
      circadian regulation of membrane potential, spontaneous action potential firing
      frequency, and pattern of Drosophila large LNvs closely resemble mammalian
      circadian neuron electrical characteristics, suggesting a general evolutionary
      conservation of both physiological and molecular oscillator mechanisms in
      pacemaker neurons.

PMID- 18077666
TI  - Effect of vertical disparities on depth representation in macaque monkeys: MT
      physiology and behavior.
AB  - Horizontal binocular disparities provide information about the distance of
      objects relative to the point of ocular fixation and must be combined with an
      estimate of viewing distance to recover the egocentric distance of an object.
      Vergence angle and the gradient of vertical disparities across the visual field
      are thought to provide independent sources of viewing distance information based
      on human behavioral studies. Although the effect of vergence angle on horizontal
      disparity selectivity in early visual cortex has been examined (with mixed
      results), the effect of the vertical disparity field has not been explored. We
      manipulated the vertical disparities in a large random-dot stimulus to simulate
      different viewing distances, and we examined the effect of this manipulation on
      both the responses of neurons in the middle temporal (MT) area and on the
      psychophysical performance of the animal in a curvature discrimination task. We
      report here that alterations to the vertical disparity field have no effect on
      the horizontal disparity tuning of MT neurons. However, the same manipulation
      strongly and systematically biases the monkey's judgments of curvature,
      consistent with previous human studies. We conclude that monkeys, like humans,
      make use of the vertical disparity field to estimate viewing distance, but that
      the physiological mechanisms for this effect occur either downstream of MT or in
      a different pathway.

PMID- 18077665
TI  - Performance monitoring local field potentials in the medial frontal cortex of
      primates: anterior cingulate cortex.
AB  - We describe intracranial local field potentials (LFP) recorded in the anterior
      cingulate cortex (ACC) of macaque monkeys performing a saccade countermanding
      task. The most prominent feature at approximately 70% of sites was greater
      negative polarity after errors than after rewarded correct trials. This negative
      polarity was also evoked in unrewarded correct trials. The LFP evoked by the
      visual target was much less polarized, and the weak presaccadic modulation was
      insufficient to control the initiation of saccades. When saccades were cancelled,
      LFP modulation decreased slightly with the magnitude of response conflict that
      corresponds to the coactivation of gaze-shifting and -holding neurons estimated
      from the probability of canceling. However, response time adjustments on
      subsequent trials were not correlated with LFP polarity on individual trials. The
      results provide clear evidence that error- and feedback-related, but not conflict
      related, signals are carried by the LFP in the macaque ACC. Finding performance
      monitoring field potentials in the ACC of macaque monkeys establishes a bridge
      between event-related potential and functional brain-imaging studies in humans
      and neurophysiology studies in non-human primates.

PMID- 18077667
TI  - Trial-by-trial updating of the gain in preparation for smooth pursuit eye
      movement based on past experience in humans.
AB  - To understand how the CNS uses past experiences to generate movements that
      accommodate minute-by-minute environmental changes, we studied the trial-by-trial
      updating of the gain for initiating smooth pursuit eye movements and how this
      relates to the history of previous trials. Ocular responses in humans elicited by
      a small perturbing motion presented 300 ms after appearance of a target were used
      as a measure of the gain of visuomotor transmission. After the perturbation, the
      target was either moved horizontally (pursuit trial) or remained in a stationary
      position (fixation trial). The trial sequence randomly included pursuit and
      fixation. The amplitude of the response to the perturbation was modulated in a
      trial-by-trial manner based on the immediately preceding trial, with preceding
      fixation and pursuit trials decreasing and increasing the gain, respectively. The
      effect of the previous trial was larger with shorter intertrial intervals, but
      did not diminish for at least 2,000 ms. A time-series analysis showed that the
      response amplitude was significantly correlated with the past few trials, with
      dynamics that could be approximated by a first-order linear system. The results
      suggest that the CNS integrates recent experiences to set the gain in preparation
      for upcoming tracking movements in a changing environment.

PMID- 18077668
TI  - Macaque V1 activity during natural vision: effects of natural scenes and
      saccades.
AB  - In the present study, we examined the way that scene complexity and saccades
      combine to sculpt the temporal response patterns of V1 neurons. To bridge the gap
      between conventional and free viewing experiments, we compared responses of
      neurons across four paradigms ranging from less to more natural. An optimal bar
      stimulus was either flashed into a receptive field (RF) or brought into it via
      saccade and was embedded in either a natural scene or a uniform gray background.
      Responses to a flashed bar tended to be higher with a uniform rather than natural
      background. The most novel result reported here is that responses evoked by
      stimuli brought into the RF via saccades were enhanced compared with the same
      stimuli flashed during steady fixation. No single factor appears to account
      entirely for this surprising effect, but there were small contributions from
      fixational saccades and residual activity carried over from the previous
      fixation. We also found a negative correlation with cells' response "history" in
      that a larger response on one fixation was associated with a lower response on
      the subsequent fixation. The effects of the natural background and saccades
      exhibited a significant nonlinear interaction with the suppressive effects of the
      natural background less for stimuli entering RFs with saccades. Together, these
      results suggest that even responses to standard optimal stimuli are difficult to
      predict under conditions similar to natural vision, and further demonstrate the
      importance of naturalistic experimental paradigms to the study of visual
      processing in V1.

PMID- 18077669
TI  - Moderate reduction of gamma-secretase: is there a therapeutic sweet spot?

PMID- 18077670
TI  - Synaptic reorganization in scaled networks of controlled size.
AB  - Neurons in plastic regions of the brain undergo fundamental changes in the number
      of cells connecting to them as a result of development, plasticity and disease.
      Across these same time periods, functional changes in cellular and synaptic
      physiology are known to occur and are often characterized as developmental
      features of these periods. However, it remains possible that many such changes
      are direct consequences of the modified degree of partnering, and that neurons
      intrinsically scale their physiological parameters with network size. To
      systematically vary a recurrent network's number of neurons while measuring its
      synaptic properties, we used microfabricated extracellular matrix adhesive
      islands created with soft lithography to culture neuronal clusters of precise
      sizes, and assessed their intrinsic connectivity using intracellular recordings
      and confocal microscopy. Both large and small clusters supported constant
      densities of excitatory and inhibitory neurons. However, neurons that were
      provided with more potential partners (larger clusters) formed more connections
      per cell via an expanded dendritic surface than cocultured smaller clusters.
      Electrophysiologically, firing rate was preserved across clusters even as size
      and synapse number increased, due in part to synapses in larger networks having
      reduced unitary strengths, and sparser paired connectivity. Larger networks also
      featured a particular increase in the number of excitatory connections onto
      inhibitory dendrites. We suggest that these specific homeostatic mechanisms,
      which match the number, strength, and architecture of connections to the number
      of total available cellular partners in the network, could account for several
      known phenomena implicated in the formation, organization and degeneration of
      neuronal circuits.

PMID- 18077671
TI  - Vestibular signals in primate thalamus: properties and origins.
AB  - Vestibular activation is found in diverse cortical areas. To characterize the
      pathways and types of signals supplied to cortex, we recorded responses to
      rotational and/or translational stimuli in the macaque thalamus. Few cells
      responded to rotation alone, with most showing convergence between semicircular
      canal and otolith signals. During sinusoidal rotation, thalamic responses lead
      head velocity by approximately 30 degrees on average at frequencies between 0.01
      4 Hz. During translation, neurons encoded combinations of linear acceleration and
      velocity. In general, thalamic responses were similar to those recorded in the
      vestibular and cerebellar nuclei using identical testing paradigms, but differed
      from those of vestibular afferents. Thalamic responses represented a biased
      continuum: most cells more strongly encoded translation and fewer cells modulated
      primarily in response to net gravitoinertial acceleration. Responsive neurons
      were scattered within a large area that included regions of the ventral posterior
      and ventral lateral nuclei, and so were not restricted to the known vestibular
      nuclei projection zones. To determine the origins of these responses, a
      retrograde tracer was injected into a dorsolateral thalamic site where
      rotation/translation-sensitive cells were encountered. This injection labeled
      neurons in the rostral contralateral anterior interposed and fastigial nuclei,
      but did not label cells within the vestibular nuclei. Examination of thalamic
      terminations after tracer injections into the cerebellar and vestibular nuclei
      indicated that most vestibular responsive units fall within the thalamic terminal
      zones of these nuclei. Thus, vestibular signals, which are supplied to the
      thalamus from both vestibular and cerebellar nuclei, are positioned for
      distribution to widespread cortical areas.

PMID- 18077672
TI  - Target cell-specific involvement of presynaptic mitochondria in post-tetanic
      potentiation at hippocampal mossy fiber synapses.
AB  - Previous studies indicate that boutons from the same axon exhibit distinct Ca2+
      dynamics depending on the postsynaptic targets. Mossy fibers of hippocampal
      granule cells innervate synaptic targets via morphologically distinct boutons. We
      investigated mitochondrial involvement in the generation of post-tetanic residual
      Ca2+ (Ca(res)) at large and small en passant mossy fiber boutons (MFBs).
      Mitochondria limited the [Ca2+]i build-up during high-frequency stimulation (HFS)
      at large MFBs, but not at small MFBs. The amount of Ca(res), quantified as a time
      integral of residual [Ca2+]i, was significantly larger at large MFBs than at
      small MFBs, and that at large MFBs was substantially attenuated by inhibitors of
      mitochondrial Ca2+ uniporter and mitochondrial Na+/Ca2+ exchanger (mitoNCX). In
      contrast, blockers of mitoNCX had no effect on the Ca(res) at small MFBs. Post
      tetanic Ca(res) has been proposed as a mechanism for post-tetanic potentiation
      (PTP). We examined mitochondrial involvement in PTP at mossy fiber synapses on
      hilar mossy cells (MF-->MC synapse) and on hilar interneurons (MF-->HI synapse),
      which are presumably innervated via large and small MFBs, respectively.
      Consistent with the differential contribution of mitochondria to Ca(res) at large
      and small MFBs, mitoNCX blockers significantly reduced the PTP at the MF-->MC
      synapse, but not at the MF-->HI synapse. In contrast, protein kinase C (PKC)
      inhibitors significantly reduced the PTP at MF-->HI synapse, but not at the MF-
      >MC synapse. These results indicate that mitochondria- and PKC-dependent PTP are
      expressed at distinct hilar mossy fiber synapses depending on postsynaptic
      targets.

PMID- 18077673
TI  - Mitochondrial sensitivity and altered calcium handling underlie enhanced NMDA
      induced apoptosis in YAC128 model of Huntington's disease.
AB  - Expansion of a CAG repeat in the Huntington's disease (HD) gene results in
      progressive neuronal loss, particularly of striatal medium-sized spiny neurons
      (MSNs). Studies in human HD autopsy brain tissue, as well as cellular and animal
      models of HD, suggest that increased activity of NMDA-type glutamate receptors
      and altered mitochondrial function contribute to selective neuronal degeneration.
      In this regard, the YAC128 mouse model, expressing full-length human huntingtin
      with 128 glutamine repeats, has been the focus of much interest. Although NMDA
      induced apoptosis is enhanced in YAC128 MSNs, here we report that the initial
      steps in the death signaling pathway, including NMDA receptor (NMDAR) current and
      cytosolic Ca2+ loading, are similar to those observed in wild-type MSNs. In
      contrast, we found that the NMDAR-mediated Ca2+ load triggered a strikingly
      enhanced loss of mitochondrial membrane potential in YAC128 MSNs, suggesting that
      NMDAR signaling via the mitochondrial apoptotic pathway is altered. This effect
      was accompanied by impaired cytosolic Ca2+ clearance after removal of NMDA, a
      difference that was not apparent after high potassium-evoked depolarization
      mediated Ca2+ entry. Inhibition of the mitochondrial permeability transition
      (mPT) reduced peak cytosolic Ca2+ and mitochondrial depolarization evoked by NMDA
      in YAC128 MSNs but not wild-type MSNs. Hence, in contrast to YAC models with
      moderate CAG expansions, the enhanced NMDA-induced apoptosis in YAC128 MSNs is
      predominantly determined by augmented mitochondrial sensitivity to Ca2+-induced
      activation of the mPT. These results suggest that the CAG repeat length
      influences the mechanism by which mHtt enhances NMDAR-mediated excitotoxicity.

PMID- 18077674
TI  - The neonatal ventromedial hypothalamus transcriptome reveals novel markers with
      spatially distinct patterning.
AB  - The ventromedial hypothalamus (VMH) is a distinct morphological nucleus involved
      in feeding, fear, thermoregulation, and sexual activity. It is essentially
      unknown how VMH circuits underlying these innate responses develop, in part
      because the VMH remains poorly defined at a cellular and molecular level.
      Specifically, there is a paucity of cell-type-specific genetic markers with which
      to identify neuronal subgroups and manipulate development and signaling in vivo.
      Using gene profiling, we now identify approximately 200 genes highly enriched in
      neonatal (postnatal day 0) mouse VMH tissue. Analyses of these VMH markers by
      real or virtual (Allen Brain Atlas; http://www.brain-map.org) experiments
      revealed distinct regional patterning within the newly formed VMH. Top neonatal
      markers include transcriptional regulators such as Vgll2, SF-1, Sox14, Satb2,
      Fezf1, Dax1, Nkx2-2, and COUP-TFII, but interestingly, the highest expressed VMH
      transcript, the transcriptional coregulator Vgll2, is completely absent in older
      animals. Collective results from zebrafish knockdown experiments and from
      cellular studies suggest that a subset of these VMH markers will be important for
      hypothalamic development and will be downstream of SF-1, a critical factor for
      normal VMH differentiation. We show that at least one VMH marker, the AT-rich
      binding protein Satb2, was responsive to the loss of leptin signaling
      (Lep(ob/ob)) at postnatal day 0 but not in the adult, suggesting that some VMH
      transcriptional programs might be influenced by fetal or early postnatal
      environments. Our study describing this comprehensive "VMH transcriptome"
      provides a novel molecular toolkit to probe further the genetic basis of innate
      neuroendocrine behavioral responses.

PMID- 18077675
TI  - Insulin dysfunction induces in vivo tau hyperphosphorylation through distinct
      mechanisms.
AB  - Hyperphosphorylated tau is the major component of paired helical filaments in
      neurofibrillary tangles found in Alzheimer's disease (AD) brains, and tau
      hyperphosphorylation is thought to be a critical event in the pathogenesis of the
      disease. The large majority of AD cases is late onset and sporadic in origin,
      with aging as the most important risk factor. Insulin resistance, impaired
      glucose tolerance, and diabetes mellitus (DM) are other common syndromes in the
      elderly also strongly age dependent, and there is evidence supporting a link
      between insulin dysfunction and AD. To investigate the possibility that insulin
      dysfunction might promote tau pathology, we induced insulin deficiency and caused
      DM in mice with streptozotocin (STZ). A mild hyperphosphorylation of tau could be
      detected 10, 20, and 30 d after STZ injection, and a massive hyperphosphorylation
      of tau was observed after 40 d. The robust hyperphosphorylation of tau was
      localized in the axons and neuropil, and prevented tau binding to microtubules.
      Neither mild nor massive tau phosphorylation induced tau aggregation. Body
      temperature of the STZ-treated mice did not differ from control animals during 30
      d, but dropped significantly thereafter. No change in beta-amyloid (Abeta)
      precursor protein (APP), APP C-terminal fragments, or Abeta levels were observed
      in STZ-treated mice; however, cellular protein phosphatase 2A activity was
      significantly decreased. Together, these data indicate that insulin dysfunction
      induced abnormal tau hyperphosphorylation through two distinct mechanisms: one
      was consequent to hypothermia; the other was temperature-independent, inherent to
      insulin depletion, and probably caused by inhibition of phosphatase activity.

PMID- 18077676
TI  - NR2A-/- mice lack long-term potentiation but retain NMDA receptor and L-type Ca2+
      channel-dependent long-term depression in the juvenile superior colliculus.
AB  - Whether the subunit composition of NMDA receptors (NMDARs) controls the direction
      of long-term plasticity is currently disputed. In the visual layers of NR2A-/-
      juvenile superior colliculus (SC), synapses lose miniature NMDAR currents,
      leaving NR2B-rich receptors in extrasynaptic regions. Compared with wild type
      (WT), evoked NMDAR currents in mutant neurons have slower rise and decay times
      and lower NMDAR/AMPAR current ratios. Moreover, NMDAR and L-type Ca2+ channel
      dependent SC long-term potentiation (LTP) is absent in NR2A-/- cells, whereas
      both WT and mutant neurons show long-duration, low-frequency-induced, long-term
      depression (LLF-LTD) that is blocked by either AP-5, nimodipine, or Ro 25-6981 [R
      (R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine
      propranol]. Thus, NMDAR currents or signaling localized at the postsynaptic
      density are essential to SC NMDAR-dependent LTP, whereas extrasynaptic or NR2B
      rich NMDARs are necessary for LLF-LTD. However, synaptic NMDARs as well as the
      NR2A subunit are missing in NR2A-/- mice. Therefore, NR2 subunit-specific ligand
      binding/channel properties and/or separate signaling pathways interacting with
      NMDARs at synaptic versus extrasynaptic receptors could underlie these results.

PMID- 18077677
TI  - Order-dependent modulation of directional signals in the supplementary and
      presupplementary motor areas.
AB  - To maximize reward and minimize effort, animals must often execute multiple
      movements in a timely and orderly manner. Such movement sequences must be usually
      discovered through experience, and during this process, signals related to the
      animal's action, its ordinal position in the sequence, and subsequent reward need
      to be properly integrated. To investigate the role of the primate medial frontal
      cortex in planning and controlling multiple movements, monkeys were trained to
      produce a series of hand movements instructed by visual stimuli. We manipulated
      the number of movements in a sequence across trials, making it possible to
      dissociate the effects of the ordinal position of a given movement and the number
      of remaining movements necessary to obtain reward. Neurons in the supplementary
      and presupplementary motor areas modulated their activity according to the number
      of remaining movements, more often than in relation to the ordinal position,
      suggesting that they might encode signals related to the timing of reward or its
      temporally discounted value. In both cortical areas, signals related to the
      number of remaining movements and those related to movement direction were often
      combined multiplicatively, suggesting that the gain of the signals related to
      movements might be modulated by motivational factors. Finally, compared with the
      supplementary motor area, neurons in the presupplementary motor area were more
      likely to increase their activity when the number of remaining movements is
      large. These results suggest that these two areas might play complementary roles
      in controlling movement sequences.

PMID- 18077678
TI  - Close homolog of L1 and neuropilin 1 mediate guidance of thalamocortical axons at
      the ventral telencephalon.
AB  - We report a cooperation between the neural adhesion molecule close homolog of L1
      (CHL1) and the semaphorin 3A (Sema3A) receptor, neuropilin 1 (Npn1), important
      for establishment of area-specific thalamocortical projections. CHL1 deletion in
      mice selectively disrupted the projection of somatosensory thalamic axons from
      the ventrobasal (VB) nuclei, causing them to shift caudally and target the visual
      cortex. At the ventral telencephalon, an intermediate target with graded Sema3A
      expression, VB axons were caudally shifted in CHL1- embryos and in Npn1(Sema-/-)
      mutants, in which axons are nonresponsive to Sema3A. CHL1 colocalized with Npn1
      on thalamic axons, and associated with Npn1 through a sequence in the CHL1 Ig1
      domain that was required for Sema3A-induced growth cone collapse. These results
      identify a novel function for CHL1 in thalamic axon responsiveness to ventral
      telencephalic cues, and demonstrate a role for CHL1 and Npn1 in establishment of
      proper targeting of specific thalamocortical projections.

PMID- 18077679
TI  - TRPM8 mechanism of cold allodynia after chronic nerve injury.
AB  - The cold- and menthol-sensitive receptor TRPM8 (transient receptor potential
      melastatin 8) has been suggested to play a role in cold allodynia, an intractable
      pain seen clinically. We studied how TRPM8 is involved in cold allodynia using
      rats with chronic constrictive nerve injury (CCI), a neuropathic pain model
      manifesting cold allodynia in hindlimbs. We found that cold allodynic response in
      the CCI animals was significantly attenuated by capsazepine, a blocker for both
      TRPM8 and TRPV1 (transient receptor potential vanilloid 1) receptors, but not by
      the selective TRPV1 antagonist I-RTX (5-iodoresiniferatoxin). In L5 dorsal root
      ganglion (DRG) sections of the CCI rats, immunostaining showed an increase in the
      percentage of TRPM8-immunoreactive neurons when compared with the sham group.
      Using the Ca2+-imaging technique and neurons acutely dissociated from the L5
      DRGs, we found that CCI resulted in a significant increase in the percentage of
      menthol- and cold-sensitive neurons and also a substantial enhancement in the
      responsiveness of these neurons to both menthol and innocuous cold. These changes
      occurred in capsaicin-sensitive neurons, a subpopulation of nociceptive-like
      neurons. Using patch-clamp recordings, we found that membrane currents evoked by
      both menthol and innocuous cold were significantly enhanced in the CCI group
      compared with the sham group. By retrograde labeling afferent neurons that target
      hindlimb skin, we showed that the skin neurons expressed TRPM8 receptors, that
      the percentage of menthol-sensitive/cold-sensitive/capsaicin-sensitive neurons
      increased, and that the menthol- and cold-evoked responses were significantly
      enhanced in capsaicin-sensitive neurons after CCI. Together, the gain of TRPM8
      mediated cold sensitivity on nociceptive afferent neurons provides a mechanism of
      cold allodynia.

PMID- 18077680
TI  - Synaptic vesicle mobility in mouse motor nerve terminals with and without
      synapsin.
AB  - We measured synaptic vesicle mobility using fluorescence recovery after
      photobleaching of FM 1-43 [N-(3-triethylammoniumpropyl)-4-(4
      (dibutylamino)styryl) pyridinium dibromide] stained mouse motor nerve terminals
      obtained from wild-type (WT) and synapsin triple knock-out (TKO) mice at room
      temperature and physiological temperature. Vesicles were mobile in resting
      terminals at physiological temperature but virtually immobile at room
      temperature. Mobility was increased at both temperatures by blocking phosphatases
      with okadaic acid, decreased at physiological temperature by blocking kinases
      with staurosporine, and unaffected by disrupting actin filaments with latrunculin
      A or reducing intracellular calcium concentration with BAPTA-AM. Synapsin TKO
      mice showed reduced numbers of synaptic vesicles and reduced FM 1-43 staining
      intensity. Synaptic transmission, however, was indistinguishable from WT, as was
      synaptic vesicle mobility under all conditions tested. Thus, in TKO mice, and
      perhaps WT mice, a phospho-protein different from synapsin but otherwise of
      unknown identity is the primary regulator of synaptic vesicle mobility.

PMID- 18077681
TI  - Transient mitogen-activated protein kinase activation is confined to a narrow
      temporal window required for the induction of two-trial long-term memory in
      Aplysia.
AB  - Although it is commonly appreciated that spaced training is superior to massed
      training in memory formation, the molecular mechanisms underlying this feature of
      memory are largely unknown. We previously described the selective benefit of
      multiple spaced (vs massed) training trials in the induction of long-term memory
      (LTM) for sensitization in Aplysia californica. We now report that LTM can be
      induced with only two spaced training trials [tail shocks (TSs)] when the second
      TS is administered 45 min after the first. In contrast, spacing intervals of 15
      and 60 min are ineffective. This surprisingly narrow permissive training window
      for two-trial LTM is accompanied by an equally narrow window of transient mitogen
      activated protein kinase (MAPK) activation, a necessary signaling molecule for
      LTM induction, at 45 min after a single TS. Thus, the transient recruitment of
      MAPK following a single TS may provide a narrow molecular window for two-trial
      LTM formation.

PMID- 18077682
TI  - GluR1 links structural and functional plasticity at excitatory synapses.
AB  - Long-term potentiation (LTP), a cellular model of learning and memory, produces
      both an enhancement of synaptic function and an increase in the size of the
      associated dendritic spine. Synaptic insertion of AMPA receptors is known to play
      an important role in mediating the increase in synaptic strength during LTP,
      whereas the role of AMPA receptor trafficking in structural changes remains
      unexplored. Here, we examine how the cell maintains the correlation between spine
      size and synapse strength during LTP. We found that cells exploit an elegant
      solution by linking both processes to a single molecule: the AMPA-type glutamate
      receptor subunit 1 (GluR1). Synaptic insertion of GluR1 is required to permit a
      stable increase in spine size, both in hippocampal slice cultures and in vivo.
      Synaptic insertion of GluR1 is not sufficient to drive structural plasticity.
      Although crucial to the expression of LTP, the ion channel function of GluR1 is
      not required for the LTP-driven spine size enhancement. Remarkably, a recombinant
      cytosolic C-terminal fragment (C-tail) of GluR1 is driven to the postsynaptic
      density after an LTP stimulus, and the synaptic incorporation of this isolated
      GluR1 C-tail is sufficient to permit spine enlargement even when postsynaptic
      exocytosis of endogenous GluR1 is blocked. We conclude that during plasticity,
      synaptic insertion of GluR1 has two functions: the established role of increasing
      synaptic strength via its ligand-gated ion channel, and a novel role through the
      structurally stabilizing effect of its C terminus that permits an increase in
      spine size.

PMID- 18077683
TI  - The cell-selective neurotoxicity of the Alzheimer's Abeta peptide is determined
      by surface phosphatidylserine and cytosolic ATP levels. Membrane binding is
      required for Abeta toxicity.
AB  - Measurement of Abeta toxicity of cells in culture exposes a subpopulation of
      cells with resistance to Abeta, even at high concentrations and after long
      periods of treatment. The cell-selective toxicity of Abeta resembles the
      selective damage observed in cells of specific regions of the Alzheimer's disease
      (AD) brain and suggests that there must be particular characteristics or stages
      of these cells that make them exceptionally sensitive or resistant to the effect
      of Abeta. Using flow cytometry and cell sorting, we efficiently separated and
      analyzed the Abeta-sensitive and the Abeta-resistant subpopulations within a
      variety of neuronal cell lines (PC12, GT1-7) and primary cultured neurons
      (hippocampal, cortex). We found that this distinctive sensitivity to Abeta was
      essentially associated with cell membrane Abeta binding. This selective Abeta
      binding was correlated to distinctive cell characteristics, such as cell membrane
      exposure of the apoptotic signal molecule phosphatidyl serine, larger cell size,
      the G1 cell cycle stage, and a lower than normal cytosolic ATP level. The
      response to Abeta by the cells with high Abeta binding affinity was characterized
      by a larger calcium response and increased mortality, lactate dehydrogenase
      release, caspase activation, and DNA fragmentation. The distinctive sensitivity
      or resistance to Abeta of the different subpopulations was maintained even after
      multiple cell divisions. We believe that these distinctive cell characteristics
      are the determining factors for the selective attack of Abeta on cells in culture
      and in the AD brain.

PMID- 18077684
TI  - Autonomic denervation of lymphoid organs leads to epigenetic immune atrophy in a
      mouse model of Krabbe disease.
AB  - Lysosomal beta-galactosylceramidase deficiency results in demyelination and
      inflammation in the nervous system causing the neurological Krabbe disease. In
      the Twitcher mouse model of this disease, we found that neurological symptoms
      parallel progressive and severe lymphopenia. Although lymphopoiesis is normal
      before disease onset, primary and secondary lymphoid organs progressively
      degenerate afterward. This occurs despite preserved erythropoiesis and leads to
      severe peripheral lymphopenia caused by reduced numbers of T cell precursors and
      mature lymphocytes. Hematopoietic cell replacement experiments support the
      existence of an epigenetic factor in mutant mice reconcilable with a progressive
      loss of autonomic axons that hampers thymic functionality. We propose that
      degeneration of autonomic nerves leads to the irreversible thymic atrophy and
      loss of immune-competence. Our study describes a new aspect of Krabbe disease,
      placing patients at risk of immune-related pathologies, and identifies a novel
      target for therapeutic interventions.

PMID- 18077685
TI  - Tonic endovanilloid facilitation of glutamate release in brainstem descending
      antinociceptive pathways.
AB  - Activation of transient receptor potential vanilloid-1 (TRPV1) channels in the
      periaqueductal gray (PAG) activates OFF antinociceptive neurons of the rostral
      ventromedial medulla (RVM). We examined in rats the effect of intra-ventrolateral
      (VL)-PAG injections of TRPV1 agonists and antagonists on the nocifensive response
      to heat in the plantar test, neurotransmitter (glutamate and GABA) release in the
      RVM, and spontaneous and tail flick-related activities of RVM neurons. The
      localization of TRPV1 in VL-PAG and RVM neurons was examined using various
      markers of glutamatergic and GABAergic neurons. Intra-VL-PAG injection of
      capsaicin increased the threshold of thermal pain sensitivity, whereas the
      selective TRPV1 antagonist 5'-iodo-resiniferatoxin (I-RTX) facilitated
      nociceptive responses, and blocked capsaicin analgesic effect at a dose inactive
      per se. Intra-VL PAG capsaicin evoked a robust release of glutamate in RVM
      microdialysates. I-RTX, at a dose inactive per se, blocked the effect of
      capsaicin, and inhibited glutamate release at a higher dose. Antinociception and
      hyperalgesia induced by capsaicin and I-RTX, respectively, correlated with
      enhanced or reduced activity of RVM OFF cells. Immunohistochemical analyses
      suggested that several TRPV1-immunoreactive (ir) neurons in both the VL-PAG and
      RVM are glutamatergic and surrounded by glutamatergic and GABAergic terminals.
      Our data suggest that VL-PAG neurons respond to TRPV1 stimulation by releasing
      glutamate into the RVM, thereby activating OFF cells and producing analgesia. The
      results obtained with the TRPV1 antagonist alone suggest that this pathway is
      tonically activated by endovanilloids.

PMID- 18077686
TI  - Neuronal activity related to reward size and rewarded target position in primate
      supplementary eye field.
AB  - Several areas of the macaque brain are known to be related to the reward during
      the performance of saccadic eye-movement tasks. Neurons in the supplementary eye
      field (SEF) have been reported to be involved in the prediction and detection of
      a reward. We describe a group of neurons in the SEF that became active during the
      period of reward delivery after saccades toward a specific direction, but showed
      weaker activity in other directions, although the same amount of reward was given
      in each direction. Moreover, this directional reward activity was modulated by
      the reward size. Our results demonstrate that the SEF cells may reflect both
      reward amount and target positions toward which a movement was rewarded, and
      suggest that they may play an important role in providing information about the
      value of each saccade according to the spatial target location.

PMID- 18077687
TI  - Semilunar granule cells: glutamatergic neurons in the rat dentate gyrus with axon
      collaterals in the inner molecular layer.
AB  - Synaptic reorganization of the dentate gyrus inner molecular layer (IML) is a
      pathophysiological process that may facilitate seizures in patients with temporal
      lobe epilepsy. Two subtypes of IML neurons were originally described by Ramon y
      Cajal (1995), but have not been thoroughly studied. We used two-photon imaging,
      infrared-differential interference contrast microscopy and patch clamp recordings
      from rat hippocampal slices to define the intrinsic physiology and synaptic
      targets of spiny, granule-like neurons in the IML, termed semilunar granule cells
      (SGCs). These neurons resembled dentate granule cells but had axon collaterals in
      the molecular layer, significantly larger dendritic arborization in the molecular
      layer, and a more triangular cell body than granule cells. Unlike granule cells,
      SGCs fired throughout long-duration depolarizing steps and had ramp-like
      depolarizations during interspike periods. Paired recordings demonstrated that
      SGCs are glutamatergic and monosynaptically excite both hilar interneurons and
      mossy cells. Semilunar granule cells appear to represent a distinct excitatory
      neuron population in the dentate gyrus that may be an important target for mossy
      fiber sprouting in patients and rodent models of temporal lobe epilepsy.

PMID- 18077688
TI  - The neural cost of the auditory perception of language switches: an event-related
      functional magnetic resonance imaging study in bilinguals.
AB  - One of the most remarkable abilities of bilinguals is to produce and/or to
      perceive a switch from one language to the other without any apparent difficulty.
      However, several psycholinguistic studies indicate that producing, recognizing,
      and integrating a linguistic code different from the one in current use may
      entail a processing cost for the speaker/listener. Up to now, the underlying
      neural substrates of perceiving language switches are unknown. In the present
      study, we investigated the neural mechanisms of language switching during
      auditory perception in bilinguals. Event-related functional magnetic resonance
      imaging was performed in 12 early, highly proficient Italian/French bilinguals,
      who were more exposed to their second language. Subjects had to listen to
      narratives containing "switched passages" that could either respect (i.e.,
      regular switches) or violate (i.e., irregular switches) the constituents of
      sentence structure. The results indicate that switching engages an extensive
      neural network, including bilateral prefrontal and temporal associative regions.
      Moreover, a clear dissociation is observed for the types of switches. Regular
      switches entail a pattern of brain activity closely related to lexical
      processing, whereas irregular switches engage brain structures involved in
      syntactic and phonological aspects of language processing. Noteworthy, when
      switching into the less-exposed language, we observed the selective engagement of
      subcortical structures and of the anterior cingulate cortex, putatively involved
      in cognitive and executive control. This suggests that switching into a less
      exposed language requires controlled processing resources. This pattern of brain
      activity may constitute an important neural signature of language dominance in
      bilinguals.

PMID- 18077689
TI  - Activin acutely sensitizes dorsal root ganglion neurons and induces hyperalgesia
      via PKC-mediated potentiation of transient receptor potential vanilloid I.
AB  - Pain hypersensitivity is a cardinal sign of tissue damage, but how molecules from
      peripheral tissues affect sensory neuron physiology is incompletely understood.
      Previous studies have shown that activin A increases after peripheral injury and
      is sufficient to induce acute nociceptive behavior and increase pain peptides in
      sensory ganglia. This study was designed to test the possibility that the
      enhanced nociceptive responsiveness associated with activin involved
      sensitization of transient receptor potential vanilloid I (TRPV1) in primary
      sensory neurons. Activin receptors were found widely distributed among adult
      sensory neurons, including those that also express the capsaicin receptor. Whole
      cell patch-clamp recording from sensory neurons showed that activin acutely
      sensitized capsaicin responses and depended on activin receptor kinase activity.
      Pharmacological studies revealed that the activin sensitization of capsaicin
      responses required PKCepsilon signaling, but not PI3K (phosphoinositide 3
      kinase), ERK (extracellular signal-regulated protein kinase), PKA, PKCalpha/beta,
      or Src. Furthermore, activin administration caused acute thermal hyperalgesia in
      wild-type mice, but not in TRPV1-null mice. These data suggest that activin
      signals through its own receptor, involves PKCepsilon signaling to sensitize the
      TRPV1 channel, and contributes to acute thermal hyperalgesia.

PMID- 18077690
TI  - Cx43 hemichannels and gap junction channels in astrocytes are regulated
      oppositely by proinflammatory cytokines released from activated microglia.
AB  - Astrocytes have a role in maintaining normal neuronal functions, some of which
      depend on connexins, protein subunits of gap junction channels and hemichannels.
      Under inflammatory conditions, microglia release cytokines, including interleukin
      1beta and tumor necrosis factor-alpha, that reduce intercellular communication
      via gap junctions. Now, we demonstrate that either conditioned medium harvested
      from activated microglia or a mixture of these two cytokines enhances the
      cellular exchange with the extracellular milieu via Cx43 hemichannels. These
      changes in membrane permeability were not detected in astrocytes cultured from
      Cx43 knock-out mice and were abrogated by connexin hemichannel blockers,
      including La3+, mimetic peptides, and niflumic acid. Both the reduction in gap
      junctional communication and the increase in membrane permeability were mediated
      by a p38 mitogen-activated protein kinase-dependent pathway. However, the
      increase in membrane permeability, but not the gap junction inhibition, was
      rapidly reversed by the sulfhydryl reducing agent dithiothreitol, indicating that
      final regulatory mechanisms are different. Treatment with proinflammatory
      cytokines reduced the total and cell surface Cx43 levels, suggesting that the
      increase in membrane permeability was attributable to an increase in hemichannels
      activity. Indeed, unitary events of approximately 220 pS corresponding to Cx43
      hemichannels were much more frequent in astrocytes treated with microglia
      conditioned medium than under control conditions. Finally, the effect of
      cytokines enhanced the uptake and reduced the intercellular diffusion of glucose,
      which might explain changes in the metabolic status of astrocytes under
      inflammatory conditions. Accordingly, this opposite regulation may affect glucose
      trafficking and certainly will modify the metabolic status of astrocytes involved
      in brain inflammation.

PMID- 18077691
TI  - Electrical stimulation of spared corticospinal axons augments connections with
      ipsilateral spinal motor circuits after injury.
AB  - Activity-dependent competition shapes corticospinal (CS) axon outgrowth in the
      spinal cord during development. An important question in neural repair is whether
      activity can be used to promote outgrowth of CS axons in maturity. After injury,
      spared CS axons sprout and make new connections, but often not enough to restore
      function. We propose that electrically stimulating spared axons after injury will
      enhance sprouting and strengthen connections with spinal motor circuits. To study
      the effects of activity, we electrically stimulated CS tract axons in the
      medullary pyramid. To study the effects of injury, one pyramid was lesioned. We
      studied sparse ipsilateral CS projections of the intact pyramid as a model of the
      sparse connections preserved after CNS injury. We determined the capacity of CS
      axons to activate ipsilateral spinal motor circuits and traced their spinal
      projections. To understand the separate and combined contributions of injury and
      activity, we examined animals receiving stimulation only, injury only, and injury
      plus stimulation. Both stimulation and injury alone strengthened CS connectivity
      and increased outgrowth into the ipsilateral gray matter. Stimulation of spared
      axons after injury promoted outgrowth that reflected the sum of effects
      attributable to activity and injury alone. CS terminations were densest within
      the ventral motor territories of the cord, and connections in these animals were
      significantly stronger than after injury alone, indicating that activity augments
      injury-induced plasticity. We demonstrate that activity promotes plasticity in
      the mature CS system and that the interplay between activity and injury
      preferentially promotes connections with ventral spinal motor circuits.

PMID- 18077692
TI  - Balanced excitatory and inhibitory inputs to cortical neurons decouple firing
      irregularity from rate modulations.
AB  - In vivo cortical neurons are known to exhibit highly irregular spike patterns.
      Because the intervals between successive spikes fluctuate greatly, irregular
      neuronal firing makes it difficult to estimate instantaneous firing rates
      accurately. If, however, the irregularity of spike timing is decoupled from rate
      modulations, the estimate of firing rate can be improved. Here, we introduce a
      novel coding scheme to make the firing irregularity orthogonal to the firing rate
      in information representation. The scheme is valid if an interspike interval
      distribution can be well fitted by the gamma distribution and the firing
      irregularity is constant over time. We investigated in a computational model
      whether fluctuating external inputs may generate gamma process-like spike
      outputs, and whether the two quantities are actually decoupled. Whole-cell patch
      clamp recordings of cortical neurons were performed to confirm the predictions of
      the model. The output spikes were well fitted by the gamma distribution. The
      firing irregularity remained approximately constant regardless of the firing rate
      when we injected a balanced input, in which excitatory and inhibitory synapses
      are activated concurrently while keeping their conductance ratio fixed. The
      degree of irregular firing depended on the effective reversal potential set by
      the balance between excitation and inhibition. In contrast, when we modulated
      conductances out of balance, the irregularity varied with the firing rate. These
      results indicate that the balanced input may improve the efficiency of neural
      coding by clamping the firing irregularity of cortical neurons. We demonstrate
      how this novel coding scheme facilitates stimulus decoding.

PMID- 18077693
TI  - Regulation of the inositol 1,4,5-trisphosphate receptor type I by O-GlcNAc
      glycosylation.
AB  - The inositol 1,4,5-trisphosphate (InsP3) receptor type I (InsP3R-I) is the
      principle channel for intracellular calcium (Ca2+) release in many cell types,
      including central neurons. It is regulated by endogenous compounds like Ca2+ and
      ATP, by protein partners, and by posttranslational modification. We report that
      the InsP3R-I is modified by O-linked glycosylation of serine or threonine
      residues with beta-N-acetylglucosamine (O-GlcNAc). The level of O-GlcNAcylation
      can be altered in vitro by the addition of the enzymes which add [OGT (O
      GlcNActransferase)] or remove (O-GlcNAcase) this sugar or by loading cells with
      UDP-GlcNAc. We monitored the effects of this modification on InsP3R function at
      the single-channel level and on intracellular Ca2+ transients. Single-channel
      activity was monitored with InsP3R incorporated into bilayers; Ca2+ signaling was
      monitored using cells loaded with a Ca2+-sensitive fluorophore. We found that
      channel activity was decreased by the addition of O-GlcNAc and that this decrease
      was reversed by removal of the sugar. Similarly, cells loaded with UDP-GlcNAc had
      an attenuated response to uncaging of InsP3. These results show that O
      GlcNAcylation is an important regulator of the InsP3R-I and suggest a mechanism
      for neuronal dysfunction under conditions in which O-GlcNAc is high, such as
      diabetes or physiological stress.

PMID- 18077694
TI  - Interaction of extracellular signal-regulated protein kinase 1/2 with actin
      cytoskeleton in supraoptic oxytocin neurons and astrocytes: role in burst firing.
AB  - Neuronal firing patterns determine the manner of neurosecretion, the underlying
      mechanisms of which are poorly understood. Using supraoptic nuclei in brain
      slices from lactating rats, we examined the involvement of extracellular signal
      regulated protein kinase 1/2 (ERK1/2) and filamentous actin (F-actin) in burst
      generation by oxytocin (OT) neurons. Blocking phosphorylation of ERK1/2 (pERK1/2)
      decreased miniature EPSCs and blocked OT-evoked bursts, as did intracellularly
      loading an antibody against pERK1/2. OT (10 pM) increased cytosolic pERK1/2 close
      to the cell membrane within the first 5 min, subsiding by 30 min, whereas OT
      elicited pERK1/2 nuclear translocation in closely associated supraoptic
      astrocytes. The increased pERK1/2 was tightly correlated with spatiotemporal
      actin dynamics. In OT neurons, OT initially increased F-actin, particularly at
      membrane subcortical areas, and then decreased it after 30 min. Both
      polymerization and depolymerization of actin cytoskeleton were associated with
      bursts, but only polymerization facilitated OT-evoked bursts. Blocking ERK1/2
      activation blocked OT-evoked actin polymerization, whereas depolymerizing F-actin
      increased pERK1/2 expression. These changes were further identified in vivo. In
      intact animals, suckling increased ERK1/2 activation in the cytosol and membrane
      subcortical area F-actin formation in OT neurons, whereas it increased F-actin
      concentration in astrocytic somata. Coimmunoprecipitation showed that suckling
      increased molecular interactions between pERK1/2 and actin. Finally, two
      different blockers of ERK1/2 kinase injected intracerebroventricularly reduced
      suckling-evoked milk ejections. This is the first demonstration that OT mediation
      of suckling-evoked bursts/milk ejections is via interactions between pERK1/2 and
      actin cytoskeleton.

PMID- 18077695
TI  - Thalamic shape abnormalities in individuals with schizophrenia and their
      nonpsychotic siblings.
AB  - Deficits in the volume of the thalamus have been observed in both individuals
      with schizophrenia and their nonpsychotic relatives. However, no studies to date
      have examined the underlying pattern of thalamic shape change in relatives of
      individuals with schizophrenia. This study examined the volume and shape of the
      thalamus in schizophrenia subjects, their siblings, and healthy control
      individuals. T1-weighted magnetic resonance scans were collected in a group of
      young subjects with schizophrenia (mean age, 23 years) and their nonpsychotic
      siblings (n = 25 pairs), and control subjects and their siblings (n = 40 pairs).
      Thalamic surfaces were generated using high-dimensional brain mapping. A
      canonical weighting function was derived from the contrast between schizophrenia
      and control subjects and then used to generate a canonical shape score for all
      subjects. Maps of the estimated surface displacement between groups were also
      created to visualize the thalamic shape differences between groups. The thalamic
      canonical scores of the siblings of the schizophrenia probands were intermediate
      between the probands and healthy control subjects. These siblings also displayed
      an intermediate degree of the inward surface deformation of the anterior and
      posterior thalamus that was present between schizophrenia probands and controls.
      There was no main effect of group status on thalamic volume and no significant
      correlations of the structural measures with measures of psychopathology or
      cognitive function. Our results indicate that thalamic shape abnormalities are
      present in relatively young individuals with schizophrenia and their siblings.
      Inward deformation of the anterior and posterior regions of the thalamus
      represents a potential neuroanatomical endophenotype of schizophrenia.

PMID- 18077696
TI  - Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity
      and spatial learning.
AB  - The NR2B subunit of the NMDA receptor interacts with several prominent proteins
      in the postsynaptic density, including calcium/calmodulin-dependent protein
      kinase II (CaMKII). To determine the function of these interactions, we derived
      transgenic mice expressing a ligand-activated carboxy-terminal NR2B fragment
      (cNR2B) by fusing this fragment to a tamoxifen (TAM)-dependent mutant of the
      estrogen receptor ligand-binding domain LBD(G521R). Here, we show that induction
      by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in
      neurons. Activation of the LBD(G521R)-cNR2B transgenic protein in mice leads to
      the disruption of CaMKII/NR2B interactions at synapses. The disruption decreases
      Thr286 phosphorylation of alphaCaMKII, lowers phosphorylation of a key CaMKII
      substrate in the postsynaptic membrane (AMPA receptor subunit glutamate receptor
      1), and produces deficits in hippocampal long-term potentiation and spatial
      learning. Together our results demonstrate the importance of interactions between
      CaMKII and NR2B for CaMKII activity, synaptic plasticity, and learning.

PMID- 18077697
TI  - Beta1 integrins in radial glia but not in migrating neurons are essential for the
      formation of cell layers in the cerebral cortex.
AB  - Radial glial cells in the cerebral cortex serve as progenitors for neurons and
      glia and guide the migration of cortical neurons. The integrin alpha3beta1 is
      thought to mediate interactions of migrating neurons with radial glial cells and
      to function as a receptor for the reelin signaling molecule. Here, we challenge
      this view and demonstrate that beta1 integrins in migrating neurons are not
      essential for the formation of cell layers in the cerebral cortex. Cortical cell
      layers also form normally in mice deficient in the integrin alpha3beta1. However,
      we provide evidence that beta1 integrins in radial glia control the morphological
      differentiation of both glia and neurons. We conclude that beta1 integrins in
      radial glia are required for the proper development of the cerebral cortex,
      whereas beta1 integrins in migrating neurons are not essential for glial-guided
      migration and reelin signaling.

PMID- 18077698
TI  - A mutation in the cone-specific pde6 gene causes rapid cone photoreceptor
      degeneration in zebrafish.
AB  - Photoreceptor degeneration is a common cause of inherited blindness worldwide. We
      have identified a blind zebrafish mutant with rapid degeneration of cone
      photoreceptors caused by a mutation in the cone phosphodiesterase c (pde6c) gene,
      a key regulatory component in cone phototransduction. Some rods also degenerate,
      primarily in areas with a low density of rods. Rod photoreceptors in areas of the
      retina that always have a high density of rods are protected from degeneration.
      Our findings demonstrate that, analogous to what happens to rod photoreceptors in
      the rd1 mouse model, loss of cone phosphodiesterase leads to rapid degeneration
      of cone photoreceptors. Furthermore, we propose that cell density plays a key
      role in determining whether rod photoreceptors degenerate as a secondary
      consequence to cone degeneration. Our zebrafish mutant serves as a model for
      developing therapeutic treatments for photoreceptor degeneration in humans.

PMID- 18077699
TI  - Exuberant neuronal convergence onto reduced taste bud targets with preservation
      of neural specificity in mice overexpressing neurotrophin in the tongue
      epithelium.
AB  - A mouse fungiform taste bud is innervated by only four to five geniculate
      ganglion neurons; their peripheral fibers do not branch to other buds. We
      examined whether the degree or specificity of this exclusive innervation pattern
      is influenced by brain-derived neurotrophic factor (BDNF), a prominent lingual
      neurotrophin implicated in taste receptoneural development. Labeled ganglion
      cells were counted after injecting single buds with different color markers in
      BDNF-lingual-overexpressing (OE) mice. To evaluate the end-organs, taste buds and
      a class of putative taste receptor cells were counted from progeny of BDNF-OE
      mice crossbred with green fluorescent protein (GFP) (gustducin) transgenic mice.
      Fungiform bud numbers in BDNF-OE mice are 35%, yet geniculate neuron numbers are
      195%, of wild-type mice. Neurons labeled by single-bud injections in BDNF-OE
      animals were increased fourfold versus controls. Injecting three buds, each with
      different color markers, resulted in predominantly single-labeled ganglion cells,
      a discrete innervation pattern similar to controls. Thus, hyper-innervation of
      BDNF-OE buds involves many neurons innervating single buds, not increased fiber
      branching. Therefore, both wild-type and BDNF-OE mice exhibit, in fungiform buds,
      the same, "discrete" receptoneural pattern, this despite dramatic neurotrophin
      overexpression-related decreases in bud numbers and increases in innervation
      density. Hyperinnervation did not affect GFP positive cell numbers; proportions
      of GFP cells in BDNF-OE buds were the same as in wild-type mice. Total numbers of
      ganglion cells innervating buds in transgenic mice are similar to controls; the
      density of taste input to the brain appears maintained despite dramatically
      reduced receptor organs and increased ganglion cells.

PMID- 18077700
TI  - Genetic contributions to long-range temporal correlations in ongoing
      oscillations.
AB  - The amplitude fluctuations of ongoing oscillations in the electroencephalographic
      (EEG) signal of the human brain show autocorrelations that decay slowly and
      remain significant at time scales up to tens of seconds. We call these long-range
      temporal correlations (LRTC). Abnormal LRTC have been observed in several brain
      pathologies, but it has remained unknown whether genetic factors influence the
      temporal correlation structure of ongoing oscillations. We recorded the ongoing
      EEG during eyes-closed rest in 390 monozygotic and dizygotic twins and
      investigated the temporal structure of ongoing oscillations in the alpha- and
      beta-frequency bands using detrended fluctuation analysis (DFA). The strength of
      LRTC was more highly correlated in monozygotic than in dizygotic twins.
      Statistical analysis attributed up to approximately 60% of the variance in DFA to
      genetic factors, indicating a high heritability for the temporal structure of
      amplitude fluctuations in EEG oscillations. Importantly, the DFA and EEG power
      were uncorrelated. LRTC in ongoing oscillations are robust, heritable, and
      independent of power, suggesting that LRTC and oscillation power are governed by
      distinct biophysical mechanisms and serve different functions in the brain. We
      propose that the DFA method is an important complement to classical spectral
      analysis in fundamental and clinical research on ongoing oscillations.

PMID- 18077701
TI  - Stepwise morphological and functional maturation of mechanotransduction in rat
      outer hair cells.
AB  - Inner ear mechanosensory hair cells convert mechanical vibrations into electrical
      signals via the coordinated interaction of multiple proteins precisely positioned
      within the sensory hair bundle. Present work identifies the time course for the
      acquisition and maturation of mechanoelectric transduction (MET) in rat cochlea
      outer hair cells maintained in organotypic cultures. A spatiotemporal
      developmental progression was observed morphologically and functionally with
      basal cochlea maturation preceding apical cochlea by 2-3 d in all measured
      properties. The fraction of mechanosensitive cells increased rapidly, with a
      midpoint at postnatal day 0 for basal cells, and correlated with myosin IIIa
      immunoreactivity. MET current magnitude increased over several days. Adaptation
      lagged the onset of transduction by a day and matured more slowly, overlapping
      but preceding the rise in myosin Ic immunoreactivity. Less than approximately 25%
      of myosin Ic expression was required for the mature adaptation response,
      suggesting multiple roles for this protein in hair bundle function. Directional
      sensitivity, lacking in immature responses, developed rapidly and correlated with
      the pruning of radial links and an increase in tenting of stereociliary tips.
      Morphological and electrophysiological data support a hypothesis in which key
      elements arrive independently at the site of MET, with a mature response
      occurring as membrane tension increases, likely by the increased tensioning of
      the tip link with the onset of adaptation. Organotypic cultures developed normal,
      tonotopically specific, MET response properties, suggesting that maturation was
      not influenced significantly by external factors such as innervation, endolymph,
      normal mechanical stimulation, or an intact organ of Corti.

PMID- 18077702
TI  - PICK1 and phosphorylation of the glutamate receptor 2 (GluR2) AMPA receptor
      subunit regulates GluR2 recycling after NMDA receptor-induced internalization.
AB  - Changes in surface trafficking of AMPA receptors play an important role in
      synaptic plasticity. Phosphorylation of the C terminus of the AMPA receptor
      (AMPAR) subunit glutamate receptor 2 (GluR2) and the binding of GluR2 to the PDZ
      [postsynaptic density-95/Discs large/zona occludens-1]-domain containing protein,
      protein interacting with protein kinase C (PICK1), have been proposed to play an
      important role in NMDA receptor dependent internalization of GluR2. However, the
      fate of internalized GluR2 after NMDA receptor (NMDAR) activation is still
      unclear. Both recycling and degradation of GluR2 after the activation of NMDAR
      have been reported. Here, we used a pH-sensitive green fluorescent protein
      variant, pHluorin, tagged to the N terminus of GluR2 (pH-GluR2) to study the
      dynamic internalization and recycling of GluR2 after NMDAR activation. Using
      fluorescence recovery after photobleach (FRAP), we directly demonstrate that
      internalized pH-GluR2 subunits recycle back to the cell surface after NMDAR
      activation. We further demonstrate that changing the phosphorylation state of the
      S880 residue at the C terminus of GluR2 does not affect NMDAR-dependent GluR2
      internalization, but alters the recycling of GluR2 after NMDAR activation. In
      addition, mutation of the N-ethylmaleimide-sensitive fusion protein (NSF) binding
      site in the pH-GluR2 slows receptor recycling. Finally, neurons lacking PICK1
      display normal NMDAR dependent GluR2 internalization compared with wild-type
      neurons, but demonstrate accelerated GluR2 recycling after NMDAR activation.
      These results indicate that phosphorylation of GluR2 S880 and NSF and PICK1
      binding to GluR2 dynamically regulate GluR2 recycling.

PMID- 18077703
TI  - cAMP response element-binding protein-mediated gene expression increases the
      intrinsic excitability of CA1 pyramidal neurons.
AB  - To investigate the role of CREB-mediated gene expression on the excitability of
      CA1 pyramidal neurons, we obtained intracellular recordings from pyramidal
      neurons of transgenic mice expressing a constitutively active form of CREB, VP16
      CREB, in a regulated and restricted manner. We found that transgene expression
      increased the neuronal excitability and inhibited the slow and medium
      afterhyperpolarization currents. These changes may contribute to the reduced
      threshold for LTP observed in these mice. When strong transgene expression was
      turned on for prolonged period of time, these mice also showed a significant loss
      of hippocampal neurons and sporadic epileptic seizures. These deleterious effects
      were dose dependent and could be halted, but not reversed by turning off
      transgene expression. Our experiments reveal a new role for hippocampal CREB
      mediated gene expression, identify the slow afterhyperpolarization as a primary
      target of CREB action, provide a new mouse model to investigate temporal lobe
      epilepsy and associated neurodegeneration, and illustrate the risks of cell death
      associated to a sustained manipulation of this pathway. As a result, our study
      has important implications for both the understanding of the cellular bases of
      learning and memory and the consideration of therapies targeted to the CREB
      pathway.

PMID- 18077704
TI  - Hepatitis C virus genotype 1a growth and induction of autophagy.
AB  - We have previously reported that immortalized human hepatocytes (IHH) support the
      generation of infectious hepatitis C virus (HCV) genotype 1a (clone H77). In the
      present study, we have investigated the growth of HCV genotype 1a (clone H77)
      through serial passages and accompanying changes in IHH in response to infection.
      Eleven serial passages of HCV genotype 1a (clone H77) in IHH were completed.
      Virus replication was ascertained from the presence of HCV-specific sequences,
      the detection of core antigen, the virus genome copy number, and the virus titer
      in IHH culture fluid. Electron microscopy suggested that HCV infection induces
      autophagic vacuole formation in IHH. Fluorescence microscopy displayed
      localization of autophagic markers, microtubule-associated protein-1 light chain
      3 and Apg5, on the vacuoles of HCV-infected hepatocytes. Taken together, our
      results suggested that HCV genotype 1a (clone H77) can be serially passaged in
      IHH and that HCV infection induces an autophagic response in hepatocytes.

PMID- 18077705
TI  - Role of APOBEC3G/F-mediated hypermutation in the control of human
      immunodeficiency virus type 1 in elite suppressors.
AB  - While many studies show that the APOBEC3 family of cytidine deaminases can
      inhibit human immunodeficiency virus type 1 (HIV-1) replication, the clinical
      significance of this host defense mechanism is unclear. Elite suppressors are HIV
      1-infected individuals who maintain viral loads below 50 copies/ml without
      antiretroviral therapy. To determine the role of APOBEC3G/F proteins in the
      control of viremia in these patients, we used a novel assay to measure the
      frequency of hypermutated proviral genomes. In most elite suppressors, the
      frequency was not significantly different than that observed in patients on
      highly active antiretroviral therapy. Thus, enhanced APOBEC3 activity alone
      cannot explain the ability of elite suppressors to control viremia.

PMID- 18077706
TI  - Coronavirus escape from heptad repeat 2 (HR2)-derived peptide entry inhibition as
      a result of mutations in the HR1 domain of the spike fusion protein.
AB  - Peptides based on heptad repeat (HR) domains of class I viral fusion proteins are
      considered promising antiviral drugs targeting virus cell entry. We have analyzed
      the evolution of the mouse hepatitis coronavirus during multiple passaging in the
      presence of an HR2-based fusion inhibitor. Drug-resistant variants emerged as a
      result of multiple substitutions in the spike fusion protein, notably within a 19
      residue segment of the HR1 region. Strikingly, one mutation, an A1006V
      substitution, which consistently appeared first in four independently passaged
      viruses, was the main determinant of the resistance phenotype, suggesting that
      only limited options exist for escape from the inhibitory effect of the HR2
      peptide.

PMID- 18077707
TI  - Cellular determinants of hepatitis C virus assembly, maturation, degradation, and
      secretion.
AB  - Intracellular infectious hepatitis C virus (HCV) particles display a distinctly
      higher buoyant density than do secreted virus particles, suggesting that the
      characteristic low density of extracellular HCV particles is acquired during
      viral egress. We took advantage of this difference to examine the determinants of
      assembly, maturation, degradation, and egress of infectious HCV particles. The
      results demonstrate that HCV assembly and maturation occur in the endoplasmic
      reticulum (ER) and post-ER compartments, respectively, and that both depend on
      microsomal transfer protein and apolipoprotein B, in a manner that parallels the
      formation of very-low-density lipoproteins (VLDL). In addition, they illustrate
      that only low-density particles are efficiently secreted and that immature
      particles are actively degraded, in a proteasome-independent manner, in a post-ER
      compartment of the cell. These results suggest that by coopting the VLDL
      assembly, maturation, degradation, and secretory machinery of the cell, HCV
      acquires its hepatocyte tropism and, by mimicry, its tendency to persist.

PMID- 18077708
TI  - Multiple displacement amplification enables large-scale clonal analysis following
      retroviral gene therapy.
AB  - Analysis of the fate of retrovirally transduced cells after transplantation is
      often hampered by the scarcity of available DNA. We evaluated a promising method
      for whole-genome amplification, called multiple displacement amplification (MDA),
      with respect to even and accurate representation of retrovirally transduced
      genomic DNA. We proved that MDA is a suitable method to subsequently quantify
      engraftment efficiencies by quantitative real-time PCR by analyzing retrovirally
      transduced DNA in a background of untransduced DNA and retroviral integrations
      found in primary material from a retroviral transplantation model. The portion of
      these retroviral integrations in the amplified samples was 1.02-fold (range 0.2,
      to 2.1-fold) the portion determined in the original genomic DNA. Integration site
      analysis by ligation-mediated PCR (LM-PCR) is essential for the detection of
      retroviral integrations. The combination of MDA and LM-PCR showed an increase in
      the sensitivity of integration site analysis, as a specific integration site
      could be detected in a background of untransduced DNA, while the transduced DNA
      made up only 0.001%. These results show for the first time that MDA enables large
      scale sensitive detection and reliable quantification of retrovirally transduced
      human genomic DNA and therefore facilitates follow-up analysis in gene therapy
      studies even from the smallest amounts of starting material.

PMID- 18077709
TI  - Heat shock perturbs TRIM5alpha restriction of human immunodeficiency virus type
      1.
AB  - TRIM5alpha restriction factors protect target cells from retroviruses by blocking
      infection prior to the accumulation of viral reverse transcription (RT) products.
      Here, we demonstrate that heat shock perturbed owl monkey TRIMCyp and rhesus
      TRIM5alpha-mediated restriction of human immunodeficiency virus type 1 (HIV-1)
      late RT products and 2-long terminal repeat circles. Heat shock partially rescued
      HIV-1 infection from TRIMCyp restriction, and this rescue became more profound
      when combined with the presence of the proteasome inhibitor MG132. This indicates
      that viral RT products rescued from restriction by either heat shock treatment or
      the presence of MG132 are on a productive pathway, supporting a model in which
      TRIM5alpha proteins restrict retroviruses in multiple phases that are
      differentially sensitive to heat shock and proteasome inhibitors.

PMID- 18077710
TI  - Expression of murine leukemia virus envelope protein is sufficient for the
      induction of apoptosis.
AB  - The generation of cytopathic effects by murine leukemia viruses (MLVs) in
      different cell types correlates with the ability of the virus to induce thymic
      lymphoma. We showed that the induction of apoptosis in mink epithelial cells by
      mink cell focus-forming (MCF) MLV infection results in the accumulation of high
      levels of both unintegrated viral DNA and the envelope precursor polyprotein
      (gPr80(env)). Comparisons of envelope protein expression levels of plasmid clones
      of the env gene of the MCF13 and noncytopathic NZB-9 MLV strains demonstrated
      that the accumulation of MCF13 gPr80(env) results in endoplasmic reticulum stress
      and is sufficient for the induction of apoptosis.

PMID- 18077711
TI  - SIAH-1 interacts with the Kaposi's sarcoma-associated herpesvirus-encoded ORF45
      protein and promotes its ubiquitylation and proteasomal degradation.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), also referred to as human
      herpesvirus 8, is a potentially tumorigenic virus implicated in the etiology of
      Kaposi's sarcoma, primary effusion lymphoma, and some forms of multicentric
      Castleman's disease. The open reading frame 45 (ORF45) protein, encoded by the
      KSHV genome, is capable of inhibiting virus-dependent interferon induction and
      appears to be essential for both early and late stages of infection. In the
      present study, we show, both in yeast two-hybrid assays and in mammalian cells,
      that the ORF45 protein interacts with the cellular ubiquitin E3 ligase family
      designated seven in absentia homologue (SIAH). We provide evidence that SIAH-1
      promotes the degradation of KSHV ORF45 through a RING domain-dependent mechanism
      and via the ubiquitin-proteasome system. Furthermore, our data indicate the
      involvement of SIAH-1 in the regulation of the expression of ORF45 in KSHV
      infected cells. Since the availability of KSHV ORF45 is expected to influence the
      course of KSHV infection, our findings identify a novel biological role for SIAH
      proteins as modulators of virus infection.

PMID- 18077712
TI  - Human immunodeficiency virus type 1 escape is restricted when conserved genome
      sequences are targeted by RNA interference.
AB  - RNA interference (RNAi) is a cellular mechanism in which small interfering RNAs
      (siRNAs) mediate sequence-specific gene silencing by cleaving the targeted mRNA.
      RNAi can be used as an antiviral approach to silence the human immunodeficiency
      virus type 1 (HIV-1) through stable expression of short-hairpin RNAs (shRNAs). We
      previously reported efficient HIV-1 inhibition by an shRNA against the
      nonessential nef gene but also described viral escape by mutation or deletion of
      the nef target sequence. The objective of this study was to obtain insight in the
      viral escape routes when essential and highly conserved sequences are targeted in
      the Gag, protease, integrase, and Tat-Rev regions of HIV-1. Target sequences were
      analyzed of more than 500 escape viruses that were selected in T cells expressing
      individual shRNAs. Viruses acquired single point mutations, occasionally
      secondary mutations, but-in contrast to what is observed with nef-no deletions
      were detected. Mutations occurred predominantly at target positions 6, 8, 9, 14,
      and 15, whereas none were selected at positions 1, 2, 5, 18, and 19. We also
      analyzed the type of mismatch in the siRNA-target RNA duplex, and G-U base pairs
      were frequently selected. These results provide insight into the sequence
      requirements for optimal RNAi inhibition. This knowledge on RNAi escape may guide
      the design and selection of shRNAs for the development of an effective RNAi
      therapy for HIV-1 infections.

PMID- 18077713
TI  - Structure of the receptor-binding protein of bacteriophage det7: a podoviral tail
      spike in a myovirus.
AB  - A new Salmonella enterica phage, Det7, was isolated from sewage and shown by
      electron microscopy to belong to the Myoviridae morphogroup of bacteriophages.
      Det7 contains a 75-kDa protein with 50% overall sequence identity to the tail
      spike endorhamnosidase of podovirus P22. Adsorption of myoviruses to their
      bacterial hosts is normally mediated by long and short tail fibers attached to a
      contractile tail, whereas podoviruses do not contain fibers but attach to host
      cells through stubby tail spikes attached to a very short, noncontractile tail.
      The amino-terminal 150 residues of the Det7 protein lack homology to the P22 tail
      spike and are probably responsible for binding to the base plate of the myoviral
      tail. Det7 tail spike lacking this putative particle-binding domain was purified
      from Escherichia coli, and well-diffracting crystals of the protein were
      obtained. The structure, determined by molecular replacement and refined at a 1.6
      A resolution, is very similar to that of bacteriophage P22 tail spike.
      Fluorescence titrations with an octasaccharide suggest Det7 tail spike to bind
      its receptor lipopolysaccharide somewhat less tightly than the P22 tail spike.
      The Det7 tail spike is even more resistant to thermal unfolding than the already
      exceptionally stable homologue from P22. Folding and assembly of both trimeric
      proteins are equally temperature sensitive and equally slow. Despite the close
      structural, biochemical, and sequence similarities between both proteins, the
      Det7 tail spike lacks both carboxy-terminal cysteines previously proposed to form
      a transient disulfide during P22 tail spike assembly. Our data suggest receptor
      binding module exchange between podoviruses and myoviruses in the course of
      bacteriophage evolution.

PMID- 18077714
TI  - Intracellular localization map of human herpesvirus 8 proteins.
AB  - Human herpesvirus 8 (HHV-8) is the etiological agent of Kaposi's sarcoma. We
      present a localization map of 85 HHV-8-encoded proteins in mammalian cells. Viral
      open reading frames were cloned with a Myc tag in expression plasmids, confirmed
      by full-length sequencing, and expressed in HeLa cells. Protein localizations
      were analyzed by immunofluorescence microscopy. Fifty-one percent of all proteins
      were localized in the cytoplasm, 22% were in the nucleus, and 27% were found in
      both compartments. Surprisingly, we detected viral FLIP (v-FLIP) in the nucleus
      and in the cytoplasm, whereas cellular FLIPs are generally localized exclusively
      in the cytoplasm. This suggested that v-FLIP may exert additional or alternative
      functions compared to cellular FLIPs. In addition, it has been shown recently
      that the K10 protein can bind to at least 15 different HHV-8 proteins. We noticed
      that K10 and only five of its 15 putative binding factors were localized in the
      nucleus when the proteins were expressed in HeLa cells individually.
      Interestingly, in coexpression experiments K10 colocalized with 87% (13 of 15) of
      its putative binding partners. Colocalization was induced by translocation of
      either K10 alone or both proteins. These results indicate active intracellular
      translocation processes in virus-infected cells. Specifically in this framework,
      the localization map may provide a useful reference to further elucidate the
      function of HHV-8-encoded genes in human diseases.

PMID- 18077715
TI  - A repetitive region of gammaherpesvirus genomic DNA is a ligand for induction of
      type I interferon.
AB  - Innate immune responses against viral infection, especially the induction of type
      I interferon, are critical for limiting the replication of the virus. Although it
      has been shown that DNA can induce type I interferon, to date no natural DNA
      ligand of a virus that induces type I interferon has been described. Here we
      screened the genome of murine gammaherpesvirus 68 with mutations at various
      genomic locations to map the region of DNA that induces type I interferon. A
      repetitive region termed the 100-base-pair repeat region is a ligand that is both
      necessary and sufficient for the viral genomic DNA to induce type I interferon. A
      region colinear with this ligand in the genome of Kaposi's sarcoma-associated
      herpesvirus also induces type I interferon. We have thus defined a repetitive
      region of the genomes of gammaherpesviruses as the first natural DNA virus ligand
      that induces type I interferon.

PMID- 18077716
TI  - Global transcriptional responses of Pseudomonas aeruginosa to phage PRR1
      infection.
AB  - The infectious cycles of viruses are known to cause dramatic changes to host cell
      function. The development of microarray technology has provided means to monitor
      host cell responses to viral infection at the level of global changes in mRNA
      levels. We have applied this methodology to investigate gene expression changes
      caused by a small, icosahedral, single-stranded-RNA phage, PRR1 (a member of the
      Leviviridae family), on its host, Pseudomonas aeruginosa, at different times
      during its growth cycle. Viral infection in this system resulted in changes in
      expression levels of <4% of P. aeruginosa genes. Interestingly, the number of
      genes affected by viral infection was significantly lower than the number of
      genes affected by changes in growth conditions during the experiment. Compared
      with a similar study that focused on the complex, double-stranded-DNA bacterial
      virus PRD1, it was evident that there were no universal responses to viral
      infection. However, in both cases, translation was affected in infected cells.

PMID- 18077717
TI  - The essential human cytomegalovirus gene UL52 is required for cleavage-packaging
      of the viral genome.
AB  - Replication of human cytomegalovirus (HCMV) produces large DNA concatemers of
      head-to-tail-linked viral genomes that upon packaging into capsids are cut into
      unit-length genomes. The mechanisms underlying cleavage-packaging and the
      subsequent steps prior to nuclear egress of DNA-filled capsids are incompletely
      understood. The hitherto uncharacterized product of the essential HCMV UL52 gene
      was proposed to participate in these processes. To investigate the function of
      pUL52, we constructed a DeltaUL52 mutant as well as a complementing cell line. We
      found that replication of viral DNA was not impaired in noncomplementing cells
      infected with the DeltaUL52 virus, but viral concatemers remained uncleaved.
      Since the subnuclear localization of the known cleavage-packaging proteins pUL56,
      pUL89, and pUL104 was unchanged in DeltaUL52-infected fibroblasts, pUL52 does not
      seem to act via these proteins. Electron microscopy studies revealed only B
      capsids in the nuclei of DeltaUL52-infected cells, indicating that the mutant
      virus has a defect in encapsidation of viral DNA. Generation of recombinant HCMV
      genomes encoding epitope-tagged pUL52 versions showed that only the N-terminally
      tagged pUL52 supported viral growth, suggesting that the C terminus is crucial
      for its function. pUL52 was expressed as a 75-kDa protein with true late
      kinetics. It localized preferentially to the nuclei of infected cells and was
      found to enclose the replication compartments. Taken together, our results
      demonstrate an essential role for pUL52 in cleavage-packaging of HCMV DNA. Given
      its unique subnuclear localization, the function of pUL52 might be distinct from
      that of other cleavage-packaging proteins.

PMID- 18077718
TI  - H5-type influenza virus hemagglutinin is functionally recognized by the natural
      killer-activating receptor NKp44.
AB  - Antiviral immune defenses involve natural killer (NK) cells. We previously showed
      that the NK-activating receptor NKp44 is involved in the functional recognition
      of H1-type influenza virus strains by NK cells. In the present study, we
      investigated the interaction of NKp44 and the hemagglutinin of a primary
      influenza virus H5N1 isolate. Here we show that recombinant NKp44 recognizes H5
      expressing cells and specifically interacts with soluble H5 hemagglutinin. H5
      pseudotyped lentiviral particles bind to NK cells expressing NKp44. Following
      interaction with target cells expressing H5, pseudotyped lentiviral particles, or
      membrane-associated H5, NK cells show NKp44-mediated induced activity. These
      findings indicate that NKp44-H5 interactions induce functional NK activation.

PMID- 18077719
TI  - Autorepression of Epstein-Barr virus nuclear antigen 1 expression by inhibition
      of pre-mRNA processing.
AB  - Epstein-Barr virus (EBV) latent infection, and its associated oncogenic
      potential, is dependent on genome maintenance functions of EBV nuclear antigen 1
      (EBNA-1), one of six EBNAs expressed from a common promoter (Wp and then Cp) upon
      infection of naive B cells. Subsequent host-mediated silencing, however,
      necessitates the expression of EBNA-1 from the EBNA-1-specific promoter Qp to
      ensure against genome loss during cell division, including EBV-associated
      malignancy. Here we addressed the mechanism by which EBNA-1 represses Qp through
      binding downstream of the transcription start site and the role of this
      autoregulatory function in EBV latency. Our results revealed that EBNA-1 does not
      inhibit transcription from Qp, as previously predicted, but acts post- or
      cotranscriptionally to block the processing of primary transcripts. This does
      not, however, require the RGG motifs responsible for strong but nonspecific RNA
      binding by EBNA-1. Within isogenic B-cell lines using either Cp/Wp or Qp, EBNA-1
      occupancy of Qp is equivalent, suggesting that autoregulation occurs, albeit to
      different degrees, during full and restricted EBV latency programs. Finally, in
      cell lines using Cp or Wp for EBNA expression, unprocessed transcripts from Qp
      are detectable in the absence of corresponding mRNAs, providing further evidence
      that this novel mechanism of EBNA-1 action functions during latency. This
      posttranscriptional mechanism of regulation would provide an efficient means to
      monitor and regulate EBNA-1 expression from Qp, ensuring levels adequate for
      genome maintenance but, perhaps more importantly, below an immunogenic threshold
      above which latently infected cells may be at risk for elimination by EBNA-1
      specific cytotoxic T cells.

PMID- 18077721
TI  - Variable transcriptional activity of endogenous retroviruses in human breast
      cancer.
AB  - Human endogenous retroviruses (HERVs) account for up to 9% of the human genome
      and include more than 800 elements related to betaretroviruses. While mouse
      mammary tumor virus (MMTV) is the accepted etiological agent of mammary tumors in
      mice, the role of retroviral elements in human breast cancer remains elusive.
      Here, we performed a comprehensive microarray-based analysis of overall
      retroviral transcriptional activities in 46 mammary gland tissue specimens
      representing pairs of nonmalignant and tumor samples from 23 patients. An
      analysis of nonmalignant tissue samples revealed a distinct, mammary gland
      specific HERV expression profile that consists of 18 constitutively active HERV
      taxa. For corresponding tumor samples, a general trend toward lower levels of
      HERV transcription was observed, suggesting common regulatory mechanisms. In
      various subsets of patients, however, increased transcript levels of single class
      I HERV families (HERV-T, HERV-E, and HERV-F) and several class II families,
      including HML-6, were detected. An analysis of transcribed HML-6 sequences
      revealed either the activation of some or the increased activity of several
      proviral loci. No evidence for MMTV or human MMTV-like virus transcripts was
      found, indicating that transcriptionally active, MMTV analogous, exogenous
      viruses were not present in the breast cancer samples analyzed.

PMID- 18077720
TI  - Genome organization and reverse genetic analysis of a type I feline coronavirus.
AB  - In this study we report the complete sequence and genome organization of the
      serotype I feline coronavirus (FCoV) strain Black. Furthermore, a reverse genetic
      system was established for this FCoV strain by cloning a full-length cDNA copy
      into vaccinia virus. This clone served as basis for the generation of recombinant
      FCoV (recFCoV) that was shown to bear the same features in vitro as the parental
      FCoV. Using this system, accessory 3abc genes in the FCoV genome were replaced by
      green fluorescent protein (recFCoV-GFP) and Renilla luciferase genes (recFCoV
      RL). In addition, we showed that feline CD14(+) blood monocytes and dendritic
      cells can be easily detected after infection with recFCoV-GFP. Thus, our
      established reverse genetic system provides a suitable tool to study the
      molecular biology of serotype I FCoV.

PMID- 18077722
TI  - CCL3 and viral chemokine-binding protein gg modulate pulmonary inflammation and
      virus replication during equine herpesvirus 1 infection.
AB  - CCL3 is a proinflammatory chemokine that mediates many of the cellular changes
      occurring in pulmonary disease. Here, CCL3(-/-) mice were used to investigate the
      role of this chemokine during respiratory herpesvirus infection. Compared to wild
      type mice, CCL3(-/-) mice infected with the alphaherpesvirus equine herpesvirus 1
      (EHV-1) displayed reduced body weight loss but had higher pulmonary viral loads.
      Lungs from infected CCL3(-/-) mice suffered a milder interstitial pneumonia, and
      fewer immune cells were recovered from the pulmonary airways after infection. We
      could also demonstrate that herpesvirus-encoded chemokine-binding glycoprotein G
      (gG) was capable of inhibiting the chemotactic functions of CCL3. This CCL3
      mediated chemotaxis, however, was restored in the presence of gG-specific
      antibodies, which puts into question the advertised use of gG deletion mutants as
      marker vaccines. In summary, we concluded that CCL3 is a major player in
      controlling herpesvirus replication in the target organ, the lung, and does so by
      evoking a strong inflammatory response. The immunomodulatory activity of CCL3 is
      balanced by the expression of viral gG, whose chemokine-binding activity is
      mitigated in secondary infections by the production of anti-gG antibodies.

PMID- 18077723
TI  - Chronic CD4+ T-cell activation and depletion in human immunodeficiency virus type
      1 infection: type I interferon-mediated disruption of T-cell dynamics.
AB  - The mechanism of CD4(+) T-cell depletion during chronic human immunodeficiency
      virus type 1 (HIV-1) infection remains unknown. Many studies suggest a
      significant role for chronic CD4(+) T-cell activation. We assumed that the
      pathogenic process of excessive CD4(+) T-cell activation would be reflected in
      the transcriptional profiles of activated CD4(+) T cells. Here we demonstrate
      that the transcriptional programs of in vivo-activated CD4(+) T cells from
      untreated HIV-positive (HIV(+)) individuals are clearly different from those of
      activated CD4(+) T cells from HIV-negative (HIV(-)) individuals. We observed a
      dramatic up-regulation of cell cycle-associated and interferon-stimulated
      transcripts in activated CD4(+) T cells of untreated HIV(+) individuals.
      Furthermore, we find an enrichment of proliferative and type I interferon
      responsive transcription factor binding sites in the promoters of genes that are
      differentially expressed in activated CD4(+) T cells of untreated HIV(+)
      individuals compared to those of HIV(-) individuals. We confirm these findings by
      examination of in vivo-activated CD4(+) T cells. Taken together, these results
      suggest that activated CD4(+) T cells from untreated HIV(+) individuals are in a
      hyperproliferative state that is modulated by type I interferons. From these
      results, we propose a new model for CD4(+) T-cell depletion during chronic HIV-1
      infection.

PMID- 18077724
TI  - Antiretroviral activity of ancestral TRIM5alpha.
AB  - The antiretroviral protein TRIM5alpha is known to have evolved different
      restriction capacities against various retroviruses, driven by positive Darwinian
      selection. However, how these different specificities have evolved in the primate
      lineages is not fully understood. Here we used ancestral protein resurrection to
      estimate the evolution of antiviral restriction specificities of TRIM5alpha on
      the primate lineage leading to humans. We used TRIM5alpha coding sequences from
      24 primates for the reconstruction of ancestral TRIM5alpha sequences using
      maximum-likelihood and Bayesian approaches. Ancestral sequences were transduced
      into HeLa and CRFK cells. Stable cell lines were generated and used to test
      restriction of a panel of extant retroviruses (human immunodeficiency virus type
      1 [HIV-1] and HIV-2, simian immunodeficiency virus [SIV] variants SIV(mac) and
      SIV(agm), and murine leukemia virus [MLV] variants N-MLV and B-MLV). The
      resurrected TRIM5alpha variant from the common ancestor of Old World primates
      (Old World monkeys and apes, approximately 25 million years before present) was
      effective against present day HIV-1. In contrast to the HIV-1 restriction
      pattern, we show that the restriction efficacy against other retroviruses, such
      as a murine oncoretrovirus (N-MLV), is higher for more recent resurrected
      hominoid variants. Ancestral TRIM5alpha variants have generally limited efficacy
      against HIV-2, SIV(agm), and SIV(mac). Our study sheds new light on the evolution
      of the intrinsic antiviral defense machinery and illustrates the utility of
      functional evolutionary reconstruction for characterizing recently emerged
      protein differences.

PMID- 18077725
TI  - Difference in receptor usage between severe acute respiratory syndrome (SARS)
      coronavirus and SARS-like coronavirus of bat origin.
AB  - Severe acute respiratory syndrome (SARS) is caused by the SARS-associated
      coronavirus (SARS-CoV), which uses angiotensin-converting enzyme 2 (ACE2) as its
      receptor for cell entry. A group of SARS-like CoVs (SL-CoVs) has been identified
      in horseshoe bats. SL-CoVs and SARS-CoVs share identical genome organizations and
      high sequence identities, with the main exception of the N terminus of the spike
      protein (S), known to be responsible for receptor binding in CoVs. In this study,
      we investigated the receptor usage of the SL-CoV S by combining a human
      immunodeficiency virus-based pseudovirus system with cell lines expressing the
      ACE2 molecules of human, civet, or horseshoe bat. In addition to full-length S of
      SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting
      different sequences of the SARS-CoV S into the SL-CoV S backbone. Several
      important observations were made from this study. First, the SL-CoV S was unable
      to use any of the three ACE2 molecules as its receptor. Second, the SARS-CoV S
      failed to enter cells expressing the bat ACE2. Third, the chimeric S covering the
      previously defined receptor-binding domain gained its ability to enter cells via
      human ACE2, albeit with different efficiencies for different constructs. Fourth,
      a minimal insert region (amino acids 310 to 518) was found to be sufficient to
      convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that
      the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and
      in function. The significance of these findings in relation to virus origin,
      virus recombination, and host switching is discussed.

PMID- 18077726
TI  - Antigenic profile of avian H5N1 viruses in Asia from 2002 to 2007.
AB  - Antigenic profiles of post-2002 H5N1 viruses representing major genetic clades
      and various geographic sources were investigated using a panel of 17 monoclonal
      antibodies raised from five H5N1 strains. Four antigenic groups from seven clades
      of H5N1 virus were distinguished and characterized based on their cross
      reactivity to the monoclonal antibodies in hemagglutination inhibition and cell
      based neutralization assays. Genetic polymorphisms associated with the variation
      of antigenicity of H5N1 strains were identified and further verified in antigenic
      analysis with recombinant H5N1 viruses carrying specific mutations in the
      hemagglutinin protein. Modification of some of these genetic variations produced
      marked improvement to the immunogenicity and cross-reactivity of H5N1 strains in
      assays utilizing monoclonal antibodies and ferret antisera raised against clade 1
      and 2 H5N1 viruses, suggesting that these sites represent antigenically
      significant amino acids. These results provide a comprehensive antigenic profile
      for H5N1 virus strains circulating in recent years and will facilitate the
      recognition of emerging antigenic variants of H5N1 virus and aid in the selection
      of vaccine strains.

PMID- 18077727
TI  - Rescue of maturation-defective flock house virus infectivity with noninfectious,
      mature, viruslike particles.
AB  - The infectivity of flock house virus (FHV) requires autocatalytic maturation
      cleavage of the capsid protein at residue 363, liberating the C-terminal 44
      residue gamma peptides, which remain associated with the particle. In vitro
      studies previously demonstrated that the amphipathic, helical portion (amino
      acids 364 to 385) of gamma is membrane active, suggesting a role for gamma in RNA
      membrane translocation during infection. Here we show that the infectivity of a
      maturation-defective mutant of FHV can be restored by viruslike particles that
      lack the genome but undergo maturation cleavage. We propose that the
      colocalization of the two defective particle types in an entry compartment allows
      the restoration of infectivity by gamma.

PMID- 18077728
TI  - Identification of three interferon-inducible cellular enzymes that inhibit the
      replication of hepatitis C virus.
AB  - Hepatitis C virus (HCV) infection is a common cause of chronic hepatitis and is
      currently treated with alpha interferon (IFN-alpha)-based therapies. However, the
      underlying mechanism of IFN-alpha therapy remains to be elucidated. To identify
      the cellular proteins that mediate the antiviral effects of IFN-alpha, we created
      a HEK293-based cell culture system to inducibly express individual interferon
      stimulated genes (ISGs) and determined their antiviral effects against HCV. By
      screening 29 ISGs that are induced in Huh7 cells by IFN-alpha and/or up-regulated
      in HCV-infected livers, we discovered that viperin, ISG20, and double-stranded
      RNA-dependent protein kinase (PKR) noncytolytically inhibited the replication of
      HCV replicons. Mechanistically, inhibition of HCV replication by ISG20 and PKR
      depends on their 3'-5' exonuclease and protein kinase activities, respectively.
      Moreover, our work, for the first time, provides strong evidence suggesting that
      viperin is a putative radical S-adenosyl-l-methionine (SAM) enzyme. In addition
      to demonstrating that the antiviral activity of viperin depends on its radical
      SAM domain, which contains conserved motifs to coordinate [4Fe-4S] cluster and
      cofactor SAM and is essential for its enzymatic activity, mutagenesis studies
      also revealed that viperin requires an aromatic amino acid residue at its C
      terminus for proper antiviral function. Furthermore, although the N-terminal 70
      amino acid residues of viperin are not absolutely required, deletion of this
      region significantly compromises its antiviral activity against HCV. Our findings
      suggest that viperin represents a novel antiviral pathway that works together
      with other antiviral proteins, such as ISG20 and PKR, to mediate the IFN response
      against HCV infection.

PMID- 18077730
TI  - Lack of a pharmacokinetic effect of raltegravir on midazolam: in vitro/in vivo
      correlation.
AB  - Raltegravir is a novel HIV-1 integrase inhibitor with potent in vitro activity
      (95% inhibitory concentration = 33 nM in 50% human serum). In vitro
      characterization of raltegravir inhibition potential was assessed against a panel
      of cytochrome P450 (CYP) enzymes. An open-label, 2-period study was conducted to
      assess the effect of raltegravir on the pharmacokinetics of midazolam, a
      sensitive CYP 3A4 probe substrate: period 1, 2.0 mg of midazolam; period 2, 400
      mg of raltegravir every 12 hours for 14 days with 2.0 mg of midazolam on day 14.
      There was no meaningful in vitro effect of raltegravir on inhibition of a panel
      of CYP enzymes and induction of CYP 3A4. In the presence of raltegravir,
      midazolam area under the curve extrapolated to infinity (AUC(0-infinity)) and
      maximum plasma concentration (C(max)) geometric mean ratios were similar
      (geometric mean ratios and 90% confidence intervals: 0.92 [0.82, 1.03] (P = .208)
      and 1.03 [0.87, 1.22] (P = .751), respectively). No substantial differences were
      observed in T(max) (P = .750) or apparent half-life (P = .533) of midazolam.
      Plasma levels of midazolam were not substantially affected by raltegravir, which
      implies that raltegravir is not a clinically important inducer or inhibitor of
      CYP 3A4 and that raltegravir would not be expected to affect the pharmacokinetics
      of other drugs metabolized by CYP 3A4 to a clinically meaningful extent.

PMID- 18077729
TI  - The picornavirus avian encephalomyelitis virus possesses a hepatitis C virus-like
      internal ribosome entry site element.
AB  - Avian encephalomyelitis virus (AEV) is a picornavirus that causes disease in
      poultry worldwide, and flocks must be vaccinated for protection. AEV is currently
      classified within the hepatovirus genus, since its proteins are most closely
      related to those of hepatitis A virus (HAV). We now provide evidence that the 494
      nucleotide-long 5' untranslated region of the AEV genome contains an internal
      ribosome entry site (IRES) element that functions efficiently in vitro and in
      mammalian cells. Unlike the HAV IRES, the AEV IRES is relatively short and
      functions in the presence of cleaved eIF4G and it is also resistant to an
      inhibitor of eIF4A. These properties are reminiscent of the recently discovered
      class of IRES elements within certain other picornaviruses, such as porcine
      teschovirus 1 (PTV-1). Like the PTV-1 IRES, the AEV IRES shows significant
      similarity to the hepatitis C virus (HCV) IRES in sequence, function, and
      predicted secondary structure. Furthermore, mutational analysis of the predicted
      pseudoknot structure at the 3' end of the AEV IRES lends support to the secondary
      structure we present. AEV is therefore another example of a picornavirus
      harboring an HCV-like IRES element within its genome, and thus, its
      classification within the hepatovirus genus may need to be reassessed in light of
      these findings.

PMID- 18077732
TI  - [1001 excuses from publisher of MFC...].

PMID- 18077731
TI  - A small scar.

PMID- 18077733
TI  - Preserving relationships with antivaccine parents: five suggestions from social
      psychology.

PMID- 18077734
TI  - Chronic disease and illness care: adding principles of family medicine to address
      ongoing health system redesign.

PMID- 18077736
TI  - Should newborns be circumcised? Yes.

PMID- 18077737
TI  - Should newborns be circumcised? No.

PMID- 18077740
TI  - Not enough vitamin D coverage.

PMID- 18077741
TI  - Debatable perspective.

PMID- 18077742
TI  - Retraction. Did we make a mistake? Can Fam Physician 2007;53:1062-3.

PMID- 18077743
TI  - Treatment of nausea and vomiting in pregnancy: an updated algorithm.
AB  - QUESTIONMy patient has severe nausea and vomiting of pregnancy (NVP). I am having
      difficulty treating her, as nothing she has tried so far has been really
      effective. I heard that there is some new information regarding the treatment of
      this condition.ANSWEREven a less severe case of NVP can have serious adverse
      effects on the quality of a woman's life, affecting her occupational, social, and
      domestic functioning, and her general well-being; therefore, it is very important
      to treat this condition appropriately and effectively. There are safe and
      effective treatments available. We have updated Motherisk's NVP algorithm to
      include recent relevant published data, and we describe some other strategies
      that deal with secondary symptoms related to NVP.

PMID- 18077744
TI  - Dermacase: tinea incoanita.

PMID- 18077745
TI  - Practice tips: choosing the correct walking aid for patients.

PMID- 18077746
TI  - Practice tips: kinder immunizations for babies.

PMID- 18077747
TI  - The motivational interview: in practice.

PMID- 18077748
TI  - Multiple opioids in pain management.

PMID- 18077749
TI  - Ear candling: should general practitioners recommend it?

PMID- 18077750
TI  - Zopiclone: is it a pharmacologic agent for abuse?
AB  - OBJECTIVE: To determine whether the hypnosedative drug zopiclone could be an
      agent for abuse. SOURCES OF INFORMATION: Using MEDLINE and PubMed, English
      language medical literature was systematically reviewed for reports of direct
      drug abuse and addiction. A review was also conducted for clinical trials or
      patient series that discussed issues of addiction or rebound effects. MAIN
      MESSAGE: Evidence of drug abuse and dependency was found in case reports and
      small patient series. Dependency symptoms of severe rebound, severe anxiety,
      tremor, palpitations, tachycardia, and seizures were observed in some patients
      after withdrawal. Abuse occurred more commonly among patients with previous drug
      abuse or psychiatric illnesses. Many clinical trials have found evidence of
      rebound insomnia after recommended dosages were stopped, albeit for a minority of
      patients. Comparative studies of zopiclone and benzodiazepines or other "Z" drugs
      are conflicting. CONCLUSION: Zopiclone has the potential for being an agent of
      abuse and addiction. While many have suggested that the addictive potential for
      this and other "Z" drugs is less than for most benzodiazepines, caution should be
      taken when prescribing this agent for insomnia. Ideally, prescriptions should be
      given for a short period of time and within the recommended dosage guidelines.

PMID- 18077751
TI  - [The implications of the hospitalist phenomenon].
AB  - OBJECTIVE: To evaluate the effect of 2 different systems of hospital care by
      means of a literature review. QUALITY OF EVIDENCE: Many areas remain unclear
      because several of the studies are opportunistic and report only isolated
      experiences or simple before-after observations. Few studies are really
      experimental, and all were conducted in academic settings, which limits their
      validity outside these settings. MAIN MESSAGE: The evidence supports the use of
      hospitalists who devote a minimum of 2 months each year to hospital work and
      practice full-time on the wards. More often than not, costs are reduced and
      better education for residents is provided with the hospitalist system. An
      important point regarding quality of care is that mortality rates are similar
      with both systems. CONCLUSION: Some questions remain unanswered. For example,
      what is the best type of training for preparing residents for hospital work and
      what is the best way for physicians to maintain their skills in this area?

PMID- 18077752
TI  - Maternal outcomes of cesarean sections: do generalists' patients have different
      outcomes than specialists' patients?
AB  - OBJECTIVE: To compare maternal outcomes of cesarean sections performed by GPs
      with the outcomes of those performed by specialists. DESIGN: Retrospective,
      comorbidity-adjusted study. SETTING: Mostly small isolated rural hospitals in
      Ontario, British Columbia, Alberta, and Saskatchewan compared with all levels of
      specialist obstetric programs offered in Canada. PARTICIPANTS: Fifteen GPs with
      less than 1 year of surgical training who performed cesarean sections. METHOD:
      Using data from the Canadian Institute for Health Information's Discharge
      Abstracts Database for the years 1990 to 2001, we matched each of 1448 cesarean
      section cases managed by these GPs to 3 cases managed by specialists and looked
      for comorbidity. In total, we analyzed the outcomes of 5792 cesarean sections.
      MAIN OUTCOME MEASURES: Composites of major morbidity possibly attributable to
      surgery:death, sepsis, cardiac arrest, shock, hypotension, ileus or bowel
      obstruction,major puerperal infection, septic or fat embolism, postpartum
      hemorrhage requiring hysterectomy, need for cardiopulmonary resuscitation, or
      another operation; and all major morbidity: major surgical morbidity, acute
      coronary syndrome, endocarditis, pulmonary edema, cerebrovascular disorder,
      pneumothorax, respiratory failure, amniotic fluid embolism, complications of
      anesthesia, deep vein thrombosis, pulmonary embolism, acute renal failure, and
      need for mechanical ventilation. RESULTS: The rate of all major morbidity was
      higher among GPs' patients than among specialists' patients (3.1% vs 1.9%, odds
      ratio [OR] 1.6, 95% confidence interval [CI] 1.1 to 2.3, P = .009) as was the
      rate of major surgical morbidity (2.5% vs 1.6%, OR 1.6, 95% CI 1.1 to 2.4, P =
      .024). Differences in major morbidity variables were not significant if major
      postpartum infection was excluded (all major morbidity 1.5% vs 1.1%, major
      surgical morbidity 1.0% vs 0.8%). Secondary outcomes included rate of transfer to
      acute care institutions (6.0% vs 1.5%, OR 4.6, 95% CI 3.6 to 6.5, P < .001), mean
      length of hospital stay (5.2 vs 4.9 days, P= .006), need for blood transfusion
      (5.9% vs 7.0%, OR 0.76, 95% CI 0.5 to 1.1, P = .11) and frequency of surgical
      error (0.8% vs 0.7%, OR 1.1, 95% CI 0.6 to 2.3, P = .72). CONCLUSION: Although
      major morbidity was higher among GPs' patients, differences were entirely
      attributable to the rate of postpartum infection. Infection rates in both groups
      were far below expected rates. The observation that blood transfusion and
      surgical error rates were similar suggests that surgical technique was not the
      cause of differences between groups. We conclude that these GPs with a mean of 4
      months' training subsequently performed cesarean sections with an acceptable
      degree of safety compared with specialists.

PMID- 18077753
TI  - Health profile of deaf Canadians: analysis of the Canada Community Health Survey.
AB  - OBJECTIVE: To profile the health of deaf and hard-of-hearing Canadians in
      relation to the population as a whole. DESIGN: Using data from the Canada
      Community Health Survey 1.1, across-sectional survey conducted by Statistics
      Canada with a total of 131,535 respondents, a series of logistic regression
      models was fitted to estimate the odds, compared with the general population, of
      respondents classified as having hearing problems reporting the presence of
      various chronic health outcomes; of their utilizing the health care system; of
      their engaging in certain health promotion activities; and of their reporting
      certain perceptions about their overall health. For each odds ratio, 95%
      confidence intervals are provided. All analyses were adjusted for age and sex
      with some analyses being restricted to appropriate age ranges or having further
      adjustments made, depending on the outcomes. MAIN OUTCOME MEASURES: In addition
      to indications of deafness or hearing loss, this study examined health care
      utilization, several commonly accepted health outcomes, engagement in health
      promotion activities, and perceptions of overall health. RESULTS: Approximately
      4% of respondents in the cross-sectional survey were considered to have hearing
      problems. The prevalence of hearing problems increased with age, with males
      having a slightly higher prevalence of hearing problems compared with females
      (4.52% versus 3.53%). Respondents classified as having hearing problems, whether
      hearing loss or deafness, were more likely to report adverse health conditions
      and low levels of physical activity, and to experience higher rates of
      depression. Respondents classified as having hearing problems were not more
      likely to smoke or to drink excessively. CONCLUSION: Communication is essential
      to both health promotion and health care delivery. Deafness-both the disability
      and the culture-creates barriers to communication. Individual practitioners can
      and should consider the communication needs of individual patients with hearing
      loss or deafness to avoid barriers to optimal health.

PMID- 18077754
TI  - [Multivitamin supplement for primary prevention of birth defects: application of
      a preventive clinical practice].
AB  - OBJECTIVE: To determine whether the recommendations health care professionals
      make to women of childbearing age on the importance of taking folic acid
      encourage these women to take folic acid supplements. DESIGN: Survey. SETTING:
      The Centre de sante et de services sociaux at the Institut universitaire de
      geriatrie de Sherbrooke in Sherbrooke, Que. PARTICIPANTS: A total of 323
      Francophone women 18 to 45 years old. MAIN OUTCOME MEASURES: Whether or not women
      had consumed vitamin and mineral supplements during the past year. Descriptive,
      bivariate statistical analyses and logistic regression modeling were carried out
      to determine whether the association between health care professionals'
      recommendations and the consumption of vitamin and mineral supplements persisted
      after controlling for certain variables (consulting documentation, knowledge,
      sources of information, perception, age, education, income, marital status, and
      plans to become pregnant). RESULTS: About 41% of the women reported that their
      physicians had recommended that they take vitamin and mineral supplements. After
      adjusting for all the variables in the model, it became clear that there was a
      significant association between the recommendations of healthcare professionals
      and the consumption of vitamins and minerals by women of childbearing age.
      CONCLUSION: Health care professionals can improve the health of the population
      through preventive clinical practices. It is important that we support them in
      their efforts to integrate and apply scientific knowledge in their practice.

PMID- 18077755
TI  - Family practice patients' adherence to statin medications.
AB  - OBJECTIVE: To measure family practice patients' adherence to statin medications
      and to identify factors associated with adherence to these medications. DESIGN:
      Cross-sectional study using a mailed self-report survey sent to 400 patients.
      SETTING: Two academic family practice clinics in Halifax, NS. PARTICIPANTS: A
      total of 284 patients aged 40 or older who were prescribed statin medications by
      their family physicians, either for the first time or as a renewal during a 20
      month period. MAIN OUTCOME MEASURES: Level of adherence to statin medications as
      measured by patients' self-report on the Morisky scale; association between high
      adherence on the Morisky scale and 38 patient-reported factors. RESULTS: Response
      rate was 82.5%. Average age of patients was 65 years, 57% were men, 62% had been
      on statin medications for more than 2 years, and 97% reported that their family
      physicians managed their cholesterol levels. More than 63% of patients reported
      high adherence as measured by the Morisky scale. On multiple logistic regression,
      being older than 65, taking 4 to 6 other prescribed medications, and having a
      lifestyle that included regular exercise or a healthy diet were significant
      independent predictors of high adherence scores on the Morisky scale. CONCLUSION:
      Almost two-thirds (63%) of patients who were prescribed statins by their family
      physicians reported high adherence to the medications. Strategies to improve
      adherence would best be directed at patients who are younger or taking fewer than
      4 or more than 6 other prescribed medications. Patients should be encouraged to
      maintain a lifestyle of regular exercise and a healthy diet, as this was
      associated with better adherence to statin medications.

PMID- 18077756
TI  - Top 10 differential diagnoses in family medicine: chest pain.

PMID- 18077757
TI  - Acute otitis media.

PMID- 18077758
TI  - Emerging vaccines: evidence and considerations for practice integration.

PMID- 18077759
TI  - The HPV vaccine: an analysis of the FUTURE II study.

PMID- 18077760
TI  - Asclepius' second chance.

PMID- 18077761
TI  - Memories of Christmas past.

PMID- 18077762
TI  - Access for all.

PMID- 18077765
TI  - 2007: the tipping point for family medicine.

PMID- 18077766
TI  - Genetic risk for myocardial infarction determined by polymorphisms of candidate
      genes in a Japanese population.
AB  - BACKGROUND: Although several environmental factors influence the development of
      myocardial infarction (MI), genetic factors have been shown to contribute to
      individual susceptibility to this condition. OBJECTIVE: To identify gene
      polymorphisms that confer susceptibility to MI in order to allow assessment of
      genetic risk for this condition. METHODS: 3433 unrelated Japanese people (1931
      men, 1502 women) were entered into the study. These comprised 1328 subjects with
      MI (1036 men, 292 women) and 2105 controls (895 men, 1210 women). The genotypes
      for 40 polymorphisms of 31 candidate genes were determined with a method that
      combines PCR and sequence-specific oligonucleotide probes with suspension array
      technology. RESULTS: The chi(2) test revealed that six polymorphisms were
      significantly (false discovery rate <0.05) related to the prevalence of MI.
      Further examination by multivariable logistic regression analysis with adjustment
      for age, sex, body mass index and the prevalence of hypertension, diabetes
      mellitus and hypercholesterolaemia, in addition to a stepwise forward selection
      procedure found that the A-->C (Gln1334His) polymorphism (rs3742207) of the
      collagen type IV alpha-1 gene (COL4A1) and the A-->G polymorphism (rs4804611) of
      the zinc finger protein 627 gene (ZNF627) were significantly (p<0.05) associated
      with the prevalence of MI. The variant C allele of COL4A1 was protective against
      MI, whereas the variant G allele of ZNF627 represented a risk factor for this
      condition. CONCLUSIONS: Determination of genotypes for COL4A1 and ZNF627 may
      prove informative for assessment of the genetic risk for MI.

PMID- 18077767
TI  - Myosin IXB gene region and gluten intolerance: linkage to coeliac disease and a
      putative dermatitis herpetiformis association.
AB  - BACKGROUND: Coeliac disease is caused by dietary gluten, which triggers chronic
      inflammation of the small intestine in genetically predisposed individuals. In
      one quarter of the patients the disease manifests in the skin as dermatitis
      herpetiformis. Recently, a novel candidate gene, myosin IXB on chromosome 19p13,
      was shown to be associated with coeliac disease in the Dutch and Spanish
      populations. The same gene has previously been associated with inflammatory bowel
      disease, systemic lupus erythematosus and rheumatoid arthritis risk, making
      myosin IXB a potential shared risk factor in these inflammatory disorders.
      METHODS: In this study, previously reported myosin IXB variants were tested for
      genetic linkage and association with coeliac disease in 495 Hungarian and Finnish
      families and in an additional 270 patients and controls. RESULTS AND CONCLUSION:
      The results show significant linkage (logarithm of odds (LOD) 3.76, p = 0.00002)
      to 19p13 which supports the presence of a genuine risk factor for coeliac disease
      in this locus. Myosin IXB variants were not associated with coeliac disease in
      this study; however, weak evidence of association with dermatitis herpetiformis
      was found. The association could not explain the strong linkage seen in both
      phenotypes, indicating that the role of other neighbouring genes in the region
      cannot be excluded. Therefore, more detailed genetic and functional studies are
      required to characterise the role of the myosin IXB gene in both coeliac disease
      and dermatitis herpetiformis.

PMID- 18077768
TI  - Integration of human papillomavirus type-16 and type-18 is a very early event in
      cervical carcinogenesis.
AB  - AIM: Human papillomavirus (HPV) integration is a critical event in cervical
      carcinogenesis. The aim of this study was to explore the physical status of HPV
      16 and HPV-18 during the progression of cervical precancerous lesions. METHODS: A
      series of 101 HPV-16 or HPV-18 positive cervical neoplasms (32 cervical
      intraepithelial neoplasia (CIN) cases and 69 cervical carcinoma (CC) cases) were
      evaluated. The physical status of both types of HPV was assessed from paraffin
      embedded formaldehyde-fixed surgical specimens by real-time PCR. RESULTS: For HPV
      16, integrated DNA was observed in 5 (83.3%) of 6 CIN I cases, 10 (90.9%) of 11
      CIN II/III cases, 29 (82.9%) of 35 FIGO (International Federation of Gynecology
      and Obstetrics) stage I CC cases and 16 (94.1%) of 17 FIGO stages II
      approximately IV CC cases. For HPV-18, integrated DNA was observed in 3 (50%) of
      6 CIN I cases, 5 (55.6%) of 9 CIN II/III cases, 9 (64.3%) of 14 FIGO stage I CC
      cases, and 1 (33.3%) of 3 FIGO stages II approximately IV CC cases. The mixed
      form of HPV DNA was the most prevalent physical state in HPV-16. There was no
      significant difference between the physical state of HPV-16 and HPV-18 DNA with
      regard to the various grades of cervical lesions. CONCLUSIONS: These data imply
      that integration of HPV-16 and HPV-18 DNA into the host genome occurs in the very
      early stage of cervical neoplastic progression. These early events may play an
      initiating role in the malignant transformation of HPV-16- and HPV-18-related low
      grade lesions into high-grade dysplasia and invasive carcinoma.

PMID- 18077769
TI  - Omeprazole-associated changes in the gastric mucosa of children.
AB  - AIMS: To describe histological findings in gastric mucosa biopsy specimens of
      children treated with proton-pump inhibitors (PPIs) for different periods of
      time. METHODS: Biopsy specimens from 12 children (aged 8 months to 15 years)
      treated with PPIs and 8 controls were processed for paraffin embedding and
      stained with H&E as well as inmmunohistochemically for sialyl-Tn antigen.
      RESULTS: The main changes were related to parietal cells which showed brisk
      cytoplasmic eosinophilia, apical cytoplasmic protrusions to dilated glands,
      cytoplasmic and nuclear hypertrophy, dilated intracytoplasmic canaliculi,
      binucleation and multinucleation. The intracellular canaliculi surface showed
      strong immunohistochemical reaction for sialyl-Tn antigen, apparently a marker
      for this structure. Some of the patients were biopsied after a short period of
      oral or intravenously administered omeprazole; the changes may therefore occur
      rapidly. CONCLUSIONS: PPIs induce the same changes in the gastric mucosa of
      children as in adults, but the number of nuclei is increased. These effects have
      not been reported previously in this age group. It is suggested that the changes
      result from a combination of effects of PPIs and gastrin release.

PMID- 18077770
TI  - Genomic aberrations and immunohistochemical markers as prognostic indicators in
      multiple myeloma.
AB  - As patients with multiple myeloma (MM) have a variable clinical course,
      predictive markers would help determine the appropriate treatment strategy.
      Clinical staging is commonly used to predict outcome, but tumour marker
      expression and the underlying genetic changes are increasingly used to assess the
      biological aggressiveness of the disease. Recent studies have demonstrated the
      utility of immunohistochemistry in detecting prognostic markers, including
      fibroblast growth factor receptor 3, cyclin D1, c-maf and p53, which have been
      associated with various genetic aberrations, including t(4;14), t(11;14),
      t(14;16) and del(17p). While t(4;14), t(14;16) and del (17p) have been documented
      to confer a poor prognosis, t(11;14) appears to be a neutral or even favourable
      factor in some studies. CD56, CD33, CD20 and CXCR4 are promising surface markers
      due to their roles in MM progression, but further studies of larger cohorts are
      necessary to assess their prognostic relevance. In this review, the biological
      function and clinical relevance of the main prognostic markers in MM is
      discussed, and also the role of immunohistochemistry in the stratification of
      patients into appropriate risk categories.

PMID- 18077771
TI  - Hereditary nonpolyposis colorectal cancer (Lynch syndrome): molecular
      pathogenesis and clinical approaches to diagnosis and management for nurses.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC), also referred to as Lynch
      syndrome, is the most common form of hereditary colorectal cancer and is
      responsible for 2% to 4% of all colorectal cancers in the Western hemisphere.
      Generally characterized by early-onset colorectal carcinoma with a mean age of
      presentation of 40 to 45 years, it can also manifest with extracolonic
      adenocarcinomas and cancers of the endometrium, ovaries, stomach, pancreas, small
      intestine, hepatobiliary tract, upper uroepithelial tract, brain, and skin. HNPCC
      is autosomal dominant and carries an 80% lifetime risk of cancer development.
      This review addresses the molecular underpinnings of HNPCC while providing a
      concise approach to clinical detection, diagnosis, and management of patients who
      may or may not test positive for an HNPCC-causing mutation. Although applicable
      to any patient-care setting in which cancer may be observed, this review
      specifically addresses the role of nurses in detecting, diagnosing, and
      clinically managing HNPCC.

PMID- 18077772
TI  - Lynch syndrome and the role of the registered nurse: commentary on "hereditary
      nonpolyposis colorectal cancer (Lynch syndrome): molecular pathogenesis and
      clinical approaches ti diagnosis and management for nurses".

PMID- 18077773
TI  - Immune responses to guided imagery during breast cancer treatment.
AB  - BACKGROUND: The use of relaxation and guided imagery to reduce stress and improve
      immune function has great potential benefits for patients with breast cancer.
      METHODS: This pilot study used a pretest-posttest experimental design with 28
      breast cancer patients, aged 25 to 75 years, with the diagnosis of stage 0, 1, or
      2 breast cancer. The experimental group received a relaxation and guided imagery
      intervention and the control group received standard care. The effects of the
      intervention on immune function were measured by natural killer (NK) cell
      cytotoxicity and IL-2-activated NK cell activity prior to surgery and 4 weeks
      postsurgery. NK cell activity was measured using a 15-hr incubation chromium
      release assay. Cytotoxicity of NK cells was measured against chromium-labeled K
      562 target cells. IL-2 was used to enhance reactivity of NK cells against tumor
      cells. After incubation for 15 hr, cytotoxicity was measured through the release
      of radioactive chromium. RESULTS: Significant differences between groups were
      found at 4 weeks postsurgery. T-tests showed increased NK cell cytotoxicity for
      the intervention group at 100:1, 50:1, and 25:1 effector cell: target cell ratios
      (E:T) (p < .01 to p < .05) and increased activation for IL-2 at 100:1, 50:1,
      25:1, and 12.5:1 (E:T) (p < .01 to p < .05) for the intervention group as
      compared to the control group. DISCUSSION: These findings suggest that a
      relaxation intervention such as guided imagery could have an effect on NK cell
      cytotoxicity and NK cell cytotoxicity after activation with IL-2 in patients
      undergoing surgery for breast cancer.

PMID- 18077774
TI  - Cervical and vaginal cytokine determinations in pregnant women: methodologic
      issues.
AB  - Investigations of the role cytokines play in preterm birth are complicated by a
      number of methodologic issues that arise as to the most feasible and efficient
      methods to measure cytokines. The purpose of this article is to review
      methodologic issues surrounding the measurement of vaginal and cervical
      cytokines, specifically IL-1beta, IL-6, and TNF-alpha, in pregnant women
      experiencing preterm labor. Specifically, two quantification methods, weight and
      protein assay, and cytokine specimens from two different sites, vaginal and
      cervical, were compared. There were no significant correlations between cytokine
      levels using the protein versus weight quantification method. The weight method
      had more negative values and thus the protein quantification method was more
      accurate. There were high correlations between cervical and vaginal IL-1beta
      levels and IL-6 levels, but cervical and vaginal TNF-alpha levels were not
      correlated.

PMID- 18077775
TI  - Characterization of T wave alternans with ambulatory electrocardiography.
AB  - T wave alternans (TWA) is a marker of ventricular electrical instability
      considered to be predictive for ventricular tachyarrhythmias. Techniques have
      been developed to detect TWA at the microv level as a method for arrhythmia risk
      stratification of persons at high risk for sudden cardiac death. Currently, TWA
      is typically calculated using spectral analysis, whereby TWA is presumed to
      assume characteristics of stationarity. In contrast, a nonspectral method known
      as modified moving average analysis is purported to detect transient TWA that
      would not be observed using a spectral approach. The purpose of this pilot study
      work was to establish the basic TWA signal properties obtained with a device
      developed by GE Medical Systems using a descriptive, correlational study design.
      Ambulatory electrocardiography (AECG) recordings (N = 24) were digitized and
      processed, and TWA was calculated via the modified moving average technique.
      Findings showed that noise was positively correlated with TWA in AECG channel 1
      (r = .899, p < .01) and AECG channel 2 (r = .758, p < .01). However, no
      significant difference (p = .237) was observed in TWA values between the AECG
      channels. A weak positive correlation was found between TWA and heart rate,
      expressed as beats per min (r = .262). Heart rate mildly predicted TWA (R =
      0.34). Nonstationarity was evaluated by testing for trend and randomness. TWA
      values measured from AECG recordings were found to be influenced moderately by
      noise and minimally by heart rate and lead placement.

PMID- 18077776
TI  - Sleep disorders, glucose regulation, and type 2 diabetes.
AB  - Recent epidemiological, biological, and behavioral evidence suggests that sleep
      disorders may contribute to the development of diabetes; conversely, diabetes
      itself may contribute to sleep disorders. Sleep appears to moderate the
      neurohormones that regulate blood glucose. Sleep deprivation and sleep disorders
      contribute to pathophysiological changes associated with the development of type
      2 diabetes. In people who already have diabetes, sleep deprivation contributes to
      elevations of hemoglobin A1c. Symptoms that occur as a result of diabetes, such
      as nocturia and neuropathic pain, may in turn contribute to sleep disturbance and
      exacerbate sleep deprivation. The purposes of this article are to examine the
      scientific basis for the associations between diabetes and sleep, identify gaps
      in the understanding of the empirical underpinnings of these relationships, and
      propose directions for future research.

PMID- 18077777
TI  - Nocturnal sleep and daytime nap behaviors in relation to salivary cortisol levels
      and temperament in preschool-age children attending child care.
AB  - The purpose of this study was to describe nocturnal sleep and daytime nap
      duration in relation to salivary cortisol levels and child temperament in
      nonproblem nappers and problem nappers. Nighttime sleep and nap durations were
      obtained with continuous actigraph recordings for 3 days and nights (Tuesday,
      Wednesday, and Thursday) on 38 children aged 3 to 5 years who attended full-day
      child care centers. Nap times and disruptive behaviors were also observed and
      coded on each of the 3 days. Parents completed a temperament scale, sleep
      diaries, and the Children's Sleep Habits Questionnaire. Salivary cortisol samples
      were collected midmorning and in the afternoon after a nap on 2 consecutive days
      (Wednesday and Thursday). Problem napping and disruptive behaviors were
      associated with more negative affect, higher afternoon cortisol levels, and a
      smaller decrement in cortisol from morning to afternoon. Problem napping and
      disruptive behaviors were also associated with longer nighttime sleep, shorter
      nap durations, and later rise times. These data provide some insight into the
      associations among nighttime sleep, napping behavior, and salivary cortisol.

PMID- 18077778
TI  - A randomized clinical trial of elk velvet antler in rheumatoid arthritis.
AB  - This article examines the effects of elk velvet antler on joint pain and
      swelling, patient/physician global assessment of disease activity, functional
      ability, quality of life, blood levels of C-reactive protein, and adverse events
      in persons with stage 2 to 3 rheumatoid arthritis experiencing residual symptoms
      after standard treatment. Patients (N=168) were enrolled in a 6-month randomized,
      triple-blind, placebo-controlled clinical trial. Instruments included the
      Arthritis Impact Measurement Scale, the Health Assessment Questionnaire, tender
      and swollen joint counts, and 100 mm-length visual analogue scales, along with
      blood tests. There were no significant differences between groups on any
      measures. The pattern of change of the measures across time points was
      essentially the same for both groups. Although some patients reported clinical
      improvements in their symptoms, there were no statistically significant
      differences between groups. Overall, elk velvet antler does not effectively
      manage residual symptoms in patients with rheumatoid arthritis.

PMID- 18077779
TI  - Anemia of chronic kidney disease.

PMID- 18077780
TI  - Contrast-induced nephropathy: is the picture any clearer?

PMID- 18077782
TI  - Novel erythropoiesis-stimulating agents: a new era in anemia management.
AB  - Nearly two decades ago, recombinant human erythropoietin transformed the
      management of chronic kidney disease anemia by allowing a more sustained increase
      in hemoglobin than was possible by intermittent blood transfusion. The treatment
      was highly effective, but because of the fairly short half-life of the molecule
      at approximately 6 to 8 h, injections usually had to be administered two to three
      times weekly. A second-generation erythropoietin analogue, darbepoetin alfa, was
      then created, with a longer elimination half-life in vivo that translated into
      less frequent dosing, usually once weekly or once every 2 wk. More recently,
      another erythropoietin-related molecule has been produced called Continuous
      Erythropoietin Receptor Activator with an even greater half-life, and other
      molecules are in development or are being licensed, including biosimilar epoetin
      products and Hematide. The latter is a synthetic peptide-based erythropoietin
      receptor agonist that, interestingly, has no structural homology with
      erythropoietin, and yet is still able to activate the erythropoietin receptor and
      stimulate erythropoiesis. The search goes on for orally active antianemic
      therapies, and several strategies are being investigated, although none is
      imminently available. This article reviews the latest progress with these novel
      erythropoietic agents in this new era in anemia management.

PMID- 18077783
TI  - Hypotheses on the etiology of antineutrophil cytoplasmic autoantibody associated
      vasculitis: the cause is hidden, but the result is known.
AB  - The first description of what is now known as antineutrophil cytoplasmic
      autoantibody-associated necrotizing vasculitis appeared more than 140 yr ago.
      Since then, many aspects of the pathogenic pathway have been elucidated,
      indicating the involvement of antineutrophil cytoplasmic autoantibodies, but why
      antineutrophil cytoplasmic autoantibodies are produced in the first place remains
      unknown. Over the years, many hypotheses have emerged addressing the etiology of
      antineutrophil cytoplasmic antibody production, but no exclusive factor or set of
      factors can so far be held responsible. Herein is reviewed the most influential
      hypotheses regarding the causes of antineutrophil cytoplasmic antibody-associated
      vasculitis with the aim of placing in an epidemiologic background the different
      hypotheses that are centered on environmental and genetic influences.

PMID- 18077784
TI  - Molecular diagnostics in autosomal dominant polycystic kidney disease: utility
      and limitations.
AB  - BACKGROUND AND OBJECTIVES: Gene-based mutation screening is now available and has
      the potential to provide diagnostic confirmation or exclusion of autosomal
      dominant polycystic kidney disease. This study illustrates its utility and
      limitations in the clinical setting. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Using a molecular diagnostic service, genomic DNA of one affected
      individual from each study family was screened for pathologic PKD1 and PKD2
      mutations. Bidirectional sequencing was performed to identify sequence variants
      in all exons and splice junctions of both genes and to confirm the specific
      mutations in other family members. In two multiplex families, microsatellite
      markers were genotyped at both PDK1 and PKD2 loci, and pair-wise and multipoint
      linkage analysis was performed. RESULTS: Three of five probands studied were
      referred for assessment of renal cystic disease without a family history of
      autosomal dominant polycystic kidney disease, and two others were younger at-risk
      members of families with autosomal dominant polycystic kidney disease being
      evaluated as living-related kidney donors. Gene-based mutation screening
      identified pathogenic mutations that provided confirmation or exclusion of
      disease in three probands, but in the other two, only unclassified variants were
      identified. In one proband in which mutation screening was indeterminate, DNA
      linkage studies provided strong evidence for disease exclusion. CONCLUSIONS: Gene
      based mutation screening or DNA linkage analysis should be considered in
      individuals in whom the diagnosis of autosomal dominant polycystic kidney disease
      is uncertain because of a lack of family history or equivocal imaging results and
      in younger at-risk individuals who are being evaluated as living-related kidney
      donors.

PMID- 18077785
TI  - Novel methods for tracking long-term maintenance immunosuppression regimens.
AB  - BACKGROUND AND OBJECTIVES: Accurate assessment of the use of immunosuppressive
      medications is vital for observational analyses that are widely used in
      transplantation research. This study assessed the accuracy of three potential
      sources of maintenance immunosuppression data. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This study investigated the agreement of immunosuppression
      information in directly linked electronic medical records for Medicare
      beneficiaries who received a kidney transplant at one center in 1998 through
      2001, Organ Procurement and Transplantation Network (OPTN) survey data, and
      Medicare pharmacy claims. Pair-wise, interdata concordance (kappa) and percentage
      agreement statistics were used to compare immunosuppression regimens reported at
      discharge, and at 6 mo and 1 yr after transplantation in each data source.
      RESULTS: Among 181 eligible participants, agreement between data sources for
      nonsteroid immunosuppression increased with time after transplantation. By 1-yr,
      concordance was excellent for calcineurin inhibitors and mycophenolate mofetil
      (kappa = 0.79 to 1.00), and very good for azathioprine (kappa = 0.73 to 0.85).
      Similarly, percentage agreement at 1 yr was 94.9 to 100% for calcineurin
      inhibitors, 91.1 to 95.7% for mycophenolate mofetil, and 87.5 to 92.8% for
      azathioprine. Widening the comparison time window resolved 33.6% of cases with
      discordant indications of calcineurin inhibitor and/or antimetabolite use in
      claims compared with other data sources. CONCLUSIONS: This analysis supports the
      accuracy of the three sources of data for description of nonsteroid
      immunosuppression after kidney transplantation. Given the current strategic focus
      on reducing collection of data, use of alternative measures of immunosuppression
      exposure is appropriate and will assume greater importance.

PMID- 18077786
TI  - Impact of the preintervention rate of renal function decline on outcome of
      renoprotective intervention.
AB  - BACKGROUND AND OBJECTIVES: Randomized clinical trials on progression of renal
      diseases usually include patients according to criteria for BP, renal function,
      and proteinuria. There are no data showing that this provides groups with similar
      baseline rates of renal function loss. Accordingly, the impact of preintervention
      rate of renal function loss (slope) on outcome of studies has not been
      established. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Preintervention slope
      was established in 60 of 89 renal patients without diabetes in whom a 4-yr
      prospective, randomized intervention had been performed (enalapril versus
      atenolol), and whether (1) preintervention slope was distributed equally over the
      groups; (2) treatment benefit, defined as slope improvement, corresponded to
      study outcome; and (3) preintervention slope was a determinant of intervention
      slope were analyzed. RESULTS: The preintervention slope was different in the
      groups: -3.7 +/- 3.2 in the group to receive enalapril versus -2.2 +/- 3.3 ml/min
      per yr in the group to receive atenolol. The intervention slopes were similar: 
      1.9 +/- 0.8 enalapril and -1.8 +/- 0.7 ml/min per yr atenolol. Accordingly, slope
      improved during enalapril only. When analyzed by angiotensin-converting enzyme
      (I/D) genotype, slope improvement was found only in DD genotype. On multivariate
      analysis, the preintervention slope was a main predictor of the intervention
      slope. CONCLUSIONS: Differences in preintervention slope are relevant to outcome
      of trials and can induce bias. For future studies, allocation according to
      preintervention slope, although time-consuming, may be useful to allow conduction
      of more valid studies in a smaller number of patients.

PMID- 18077787
TI  - Requirement for CD1d expression by B cells to stimulate NKT cell-enhanced
      antibody production.
AB  - Activation of natural killer-like T (NKT) cells with the CD1d ligand alpha
      galactosylceramide enhances T-dependent humoral immune responses against
      coadministered T-dependent Ag. At present, there is little information on the
      mechanisms involved other than a dependence on CD1d expression by antigen
      presenting cells and/or development of the NKT subset. We therefore tested the
      hypothesis that direct presentation of alpha-GC by B cells was required for NKT
      enhanced Ab responses against T-dependent Ag. We reconstituted B cell-deficient
      microMT mice with B cells from C57Bl/6 donors or CD1d(-/-) donors before
      immunization with NP-KLH alone or NP-KLH mixed with alpha-GC. We made the
      surprising observation that B-cell expression of CD1d is absolutely required for
      the NKT-enhanced Ab response. Our data show that the mechanism by which NKT cells
      enhance humoral immune responses involves interaction with CD1d-expressing B
      cells.

PMID- 18077788
TI  - Indoleamine 2,3-dioxygenase is a critical regulator of acute graft-versus-host
      disease lethality.
AB  - Graft-versus-host disease (GVHD) is initiated after activation of donor T cells
      by host antigen-presenting cells (APCs). The immunosuppressive enzyme indoleamine
      2,3-dioxygenase (IDO) is expressed by APCs and parenchymal cells and is further
      inducible by inflammation. We investigated whether lethal conditioning and GVHD
      induce IDO and if IDO prevents tissue injury by suppressing immune responses at
      the induction site. We determined that IDO is a critical regulator of GVHD, most
      strikingly in the colon, where epithelial cells dramatically up-regulated IDO
      expression during GVHD. IDO(-/-) mice died more quickly from GVHD, displaying
      increased colonic inflammation and T-cell infiltration. GVHD protection was not
      mediated by control of T-cell proliferation, apoptosis, or effector mechanisms in
      lymphoid organs, nor did it require donor T regulatory cells. Instead, T cells in
      IDO(-/-) colons underwent increased proliferation and decreased apoptosis
      compared with their wild-type counterparts. This evidence suggests that IDO can
      act at the site of expression to decrease T-cell proliferation and survival,
      diminishing colonic inflammation and reducing disease severity. These studies are
      the first to identify a function for IDO in GVHD lethality and indicate that
      modulation of the IDO pathway may be an effective strategy for treatment of this
      disease.

PMID- 18077789
TI  - Interleukin-2, interleukin-12, and interferon-gamma levels and risk of young
      adult Hodgkin lymphoma.
AB  - Young adult Hodgkin lymphoma (YAHL) is associated clinically with altered
      immunity, including a systemic defect in cell-mediated responses. There is strong
      evidence of a genetic contribution to risk, so we hypothesized that heritable
      alterations in cytokine production associated with Th1 function may contribute to
      susceptibility. We identified twin pairs in whom at least one member had YAHL and
      measured interleukin-2 (IL-2), interleukin-12 (IL-12), and interferon-gamma (IFN
      gamma) levels in PHA-stimulated peripheral blood mononuclear cell supernatant in
      90 case-twins, 84 of their disease-free twins (unaffected cotwins), and 90
      matched controls. Mean difference and mean percentage difference in cytokine
      levels between case-twins and controls, and unaffected cotwins and controls were
      determined using analysis of covariance. YAHL case-twins and their unaffected
      cotwins had IL-12 levels that were 60.6% (P=.002) and 49% (P=.04) lower than
      those of their matched controls, respectively. IL-2 levels were significantly
      higher in case-twins (P=.049), but not unaffected cotwins (P=.57), compared with
      controls. Differences in IFN-gamma levels were not statistically significant in
      either comparison. An IL-12 polymorphism known to regulate expression was
      associated with a 2.8-fold (P=.03) increase in YAHL risk. Thus, both case-twins
      and their unaffected cotwins had a decreased ability to produce IL-12, which may
      contribute to YAHL susceptibility.

PMID- 18077790
TI  - Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are
      highly expressed in the activated B cell-like subtype of DLBCL.
AB  - The FOXP1 forkhead transcription factor is targeted by recurrent chromosome
      translocations in several subtypes of B-cell non-Hodgkin lymphomas, where high
      level FOXP1 protein expression has been linked to a poor prognosis. Western
      blotting studies of diffuse large B-cell lymphoma (DLBCL) cell lines unexpectedly
      identified the atypical high-level expression of 2 smaller, 60 to 65 kDa, FOXP1
      isoforms in all 5 of those with the activated B cell (ABC)-like DLBCL subtype and
      in a subgroup of primary DLBCL. The anti-FOXP1 (JC12) monoclonal antibody cannot
      distinguish FOXP1 isoforms by immunohistochemistry, a finding that may be
      clinically relevant as high-level expression of the full-length FOXP1 protein was
      observed in some germinal center-derived DLBCLs. ABC-like DLBCL-derived cell
      lines were observed to express 2 novel, alternatively spliced FOXP1 mRNA
      isoforms, encoding N-terminally truncated proteins. These transcripts and the
      smaller protein isoforms were induced as a consequence of normal B-cell
      activation, which thus represents an additional mechanism for up-regulating FOXP1
      expression in lymphomas. The expression of potentially oncogenic smaller FOXP1
      isoforms may resolve the previously contradictory findings that FOXP1 represents
      a favorable prognostic marker in breast cancer and an adverse risk factor in B
      cell lymphomas.

PMID- 18077792
TI  - Changes in the expression of telomere maintenance genes suggest global telomere
      dysfunction in B-chronic lymphocytic leukemia.
AB  - In this study, we explored the telomeric changes that occur in B-chronic
      lymphocytic leukemia (B-CLL), in which telomere length has recently been
      demonstrated to be a powerful prognostic marker. We carried out a transcriptomic
      analysis of telomerase components (hTERT and DYSKERIN), shelterin proteins (TRF1,
      TRF2, hRAP1, TIN2, POT1, and TPP1), and a set of multifunctional proteins
      involved in telomere maintenance (hEST1A, MRE11, RAD50, Ku80, and RPA1) in
      peripheral B cells from 42 B-CLL patients and 20 healthy donors. We found that,
      in B-CLL cells, the expressions of hTERT, DYSKERIN, TRF1, hRAP1, POT1, hEST1A,
      MRE11, RAD50, and KU80 were more than 2-fold reduced (P < .001), contrasting with
      the higher expression of TPP1 and RPA1 (P < .001). This differential expression
      pattern suggests that both telomerase down-regulation and changes in telomeric
      proteins composition are involved in the pathogenesis of B-CLL.

PMID- 18077793
TI  - A new look at platelet-derived growth factor in renal disease.
AB  - The PDGF system, comprising four isoforms (PDGF-A, -B, -C, and -D) and two
      receptor chains (PDGFR-alpha and -beta), plays important roles in wound healing,
      atherosclerosis, fibrosis, and malignancy. Components of the system are expressed
      constitutively or inducibly in most renal cells. They regulate a multitude of
      pathophysiologic events, ranging from cell proliferation and migration to
      extracellular matrix accumulation, production of pro- and anti-inflammatory
      mediators, tissue permeability, and regulation of hemodynamics. Genetic deletion
      of PDGF-B or PDGFR-beta results in an absent glomerular mesangium, whereas PDGF-C
      and PDGFR-alpha contribute to the formation of the renal cortical interstitium.
      Almost all experimental and human renal diseases are characterized by altered
      expression of components of the PDGF system. Infusion or systemic overexpression
      of PDGF-B or -D induces prominent mesangioproliferative changes and renal
      fibrosis. Intervention studies identified PDGF-C as a mediator of renal
      interstitial fibrosis and PDGF-B and -D as key factors involved in
      mesangioproliferative disease and renal interstitial fibrosis. These data
      establish PDGF as one of the best characterized growth factors in renal disease
      and the most potent stimulus of mesangial cell proliferation currently
      identified. Accordingly, targeted intervention against the various PDGF isoforms
      offers a promising novel therapeutic approach to renal disease.

PMID- 18077791
TI  - Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated
      with anti-CD20 immunochemotherapy: results from randomized trials of the European
      MCL Network and the German Low Grade Lymphoma Study Group.
AB  - Clinical outcome of mantle cell lymphoma (MCL) is highly heterogeneous. Tumor
      cell proliferation as assessed by the Ki-67 index has been shown to yield
      prognostic information on MCL in many studies using heterogeneously treated
      patient cohorts. The prognostic value of the Ki-67 index in patients treated with
      anti-CD20 therapy has not been studied so far. We analyzed the Ki-67 index at
      primary diagnosis in 249 advanced-stage MCL patients treated within randomized
      trials. Ki-67 showed high prognostic relevance for overall survival (relative
      risk 1.27 for 10% higher Ki-67, P < .001), also independently from clinical
      prognostic factors. The 3 groups with different Ki-67 index of less than 10%, 10%
      to less than 30%, and 30% or more showed significantly different overall survival
      in patients treated with CHOP (P = .001) as well as in patients treated with CHOP
      in combination with anti-CD20 therapy (R-CHOP, P = .013). Thus, the Ki-67 index
      remains an important prognostic marker in the era of anti-CD20 therapy. The Euro
      pean MCL study is registered at www.ClinicalTrials.gov as #NCT00016887.

PMID- 18077794
TI  - Variability of brain death determination guidelines in leading US neurologic
      institutions.
AB  - BACKGROUND: In accordance with the Uniform Determination of Death Act, guidelines
      for brain death determination are developed at an institutional level,
      potentially leading to variability of practice. We evaluated the differences in
      brain death guidelines in major US hospitals with a strong presence of neurology
      and neurosurgery to determine whether there was evidence of variation from the
      guidelines as put forth by the American Academy of Neurology (AAN). METHODS: We
      requested the guidelines for determination of death by brain criteria from the US
      News and World Report top 50 neurology/neurosurgery institutions in 2006. We
      evaluated the guidelines for five categories of data: guideline performance,
      preclinical testing, clinical examination, apnea testing, and ancillary tests. We
      compared the guidelines directly with the AAN guidelines for
      consistencies/differences. RESULTS: There was an 82% response rate to requests.
      Major discrepancies were present among institutions for all five categories.
      Variability existed in the guidelines' requirements for performance of the
      evaluation, prerequisites prior to testing, specifics of the brainstem
      examination and apnea testing, and what types of ancillary tests could be
      performed, including what pitfalls or limitations might exist. CONCLUSIONS: Major
      differences exist in brain death guidelines among the leading neurologic
      hospitals in the Unites States. Adherence to the American Academy of Neurology
      guidelines is variable. If the guidelines reflect actual practice at each
      institution, there are substantial differences in practice which may have
      consequences for the determination of death and initiation of transplant
      procedures.

PMID- 18077795
TI  - Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in
      Cholesterol Levels study.
AB  - BACKGROUND: In the Stroke Prevention by Aggressive Reduction in Cholesterol
      Levels (SPARCL) study, atorvastatin 80 mg/day reduced the risk of stroke in
      patients with recent stroke or TIA. Post hoc analysis found this overall benefit
      included an increase in the numbers of treated patients having hemorrhagic stroke
      (n = 55 for active treatment vs n = 33 for placebo). METHODS: We explored the
      relationships between hemorrhage risk and treatment, baseline patient
      characteristics, most recent blood pressure, and most recent low-density
      lipoprotein (LDL) cholesterol levels prior to the hemorrhage. RESULTS: Of 4,731
      patients, 67% had ischemic strokes, 31% TIAs, and 2% hemorrhagic strokes as entry
      events. In addition to atorvastatin treatment (HR 1.68, 95% CI 1.09 to 2.59, p =
      0.02), Cox multivariable regression including baseline variables significant in
      univariable analyses showed that hemorrhagic stroke risk was higher in those
      having a hemorrhagic stroke as the entry event (HR 5.65, 95% CI 2.82 to 11.30, p
      < 0.001), in men (HR 1.79, 95% CI 1.13 to 2.84, p = 0.01), and with age (10 y
      increments, HR 1.42, 95% CI 1.16 to 1.74, p = 0.001). There were no statistical
      interactions between these factors and treatment. Multivariable analyses also
      found that having Stage 2 (JNC-7) hypertension at the last study visit before a
      hemorrhagic stroke increased risk (HR 6.19, 95% CI 1.47 to 26.11, p = 0.01), but
      there was no effect of most recent LDL-cholesterol level in those treated with
      atorvastatin. CONCLUSIONS: Hemorrhagic stroke was more frequent in those treated
      with atorvastatin, in those with a hemorrhagic stroke as an entry event, in men,
      and increased with age. Those with Stage 2 hypertension at the last visit prior
      to the hemorrhagic stroke were also at increased risk. Treatment did not
      disproportionately affect the hemorrhagic stroke risk associated with these other
      factors. There were no relationships between hemorrhage risk and baseline low
      density lipoprotein (LDL) cholesterol level or recent LDL cholesterol level in
      treated patients.

PMID- 18077796
TI  - Associations of job demands and intelligence with cognitive performance among men
      in late life.
AB  - OBJECTIVE: To examine the association of job characteristics and intelligence to
      cognitive status in members of the National Academy of Sciences-National Research
      Council Twins Registry of World War II veterans. METHODS: Participants (n =
      1,036) included individuals with an assessment of intelligence based on Armed
      Services testing in early adulthood. In late adulthood, these individuals
      completed the modified Telephone Interview for Cognitive Status (TICS-m) and
      occupational history as part of an epidemiologic study of aging and dementia.
      Occupational history was coded to produce a matrix of job characteristics. Based
      on factor analysis, job characteristics were interpreted as reflecting general
      intellectual demands (GI), human interaction and communication (HC), physical
      activity (PA), and visual attention (VA). RESULTS: Based on regression analysis
      of TICS-m score covarying for age, intelligence, and years of education, higher
      levels of GI and HC were independently associated with higher TICS-m performance,
      whereas higher PA was independently associated with lower performance. There was
      an interaction of GI and intelligence, indicating that individuals at the lower
      range of intellectual aptitude in early adulthood derived greater cognitive
      benefit from intellectually demanding work. CONCLUSIONS: Intellectually demanding
      work was associated with greater benefit to cognitive performance in later life
      independent of related factors like education and intelligence. The fact that
      individuals with lower intellectual aptitude demonstrated a stronger positive
      association between work and higher cognitive performance during retirement
      suggests that behavior may enhance intellectual reserve, perhaps even years after
      peak intellectual activity.

PMID- 18077797
TI  - Adjunctive lamotrigine for partial seizures in patients aged 1 to 24 months.
AB  - OBJECTIVE: This randomized, double-blind, placebo-controlled trial was conducted
      to assess the efficacy and tolerability of adjunctive lamotrigine for the
      treatment of partial seizures in infants aged 1 to 24 months. METHODS: The study
      used a responder-enriched design in which all patients received adjunctive
      lamotrigine during an open-label phase (n = 177; maximum maintenance dose 5.1
      mg/kg/day for those on non-enzyme-inducing antiepileptic drugs [AEDs] or
      valproate and 15.6 mg/kg/day for those on enzyme-inducing AEDs). Patients meeting
      response criteria were randomly assigned to double-blind treatment for up to 8
      weeks with continued lamotrigine (n = 19) or to withdrawal from lamotrigine
      (placebo; n = 19) while background AEDs were maintained. RESULTS: The proportion
      of treatment failures (patients who met escape criteria or withdrew before
      completing the double-blind phase) was lower with lamotrigine (58%) than with
      placebo (84%). This finding was not significant in the primary analysis (two
      sided chi(2) test [primary endpoint]). A post hoc sensitivity analysis of the
      primary endpoint was also performed (p = 0.045 by one-sided, mid-p corrected
      Fisher exact test). The median time to meet escape criteria was longer with
      lamotrigine (42 days) than with placebo (22 days) (p = 0.059). During the last 28
      days of the open-label phase, 53% of the patients had a >or=50% reduction in
      frequency of partial seizures with lamotrigine. Additional reduction in partial
      seizure frequency was observed during the double-blind phase compared with the
      last 4 weeks of the open-label phase among those randomly assigned to lamotrigine
      (32% with a >or=25% reduction) but not those randomly assigned to placebo (5%
      with a >or=25% reduction). Lamotrigine was well tolerated, with an adverse event
      profile comparable to that observed in older pediatric patients. CONCLUSION:
      Lamotrigine was well tolerated, and the data indicate that it may be efficacious
      in the treatment of partial seizures in infants aged 1 to 24 months.

PMID- 18077798
TI  - The "mirror-neuron system" in MS: A 3 tesla fMRI study.
AB  - OBJECTIVE: The mirror neuron system (MNS) is an observation-execution matching
      system activated, in humans, during action observation, motor learning, and
      imitation of action. We used functional MRI (fMRI) to investigate the properties
      of the MNS in patients with multiple sclerosis (MS). METHODS: Using a 3 tesla
      scanner, we acquired fMRI in 16 right-handed patients with relapsing-remitting MS
      and 14 controls. Two motor tasks were studied. The first consisted of repetitive
      flexion-extension of the last four fingers of the right hand (simple task)
      alternated to epochs of rest; the second (MNS task) consisted of observation of a
      movie showing the hand of another subject while performing the same task.
      RESULTS: During the simple task, compared to controls, patients with MS had more
      significant activations of the contralateral primary sensorimotor cortex and
      supplementary motor area. During the MNS task, both groups showed the activation
      of several visual areas, the infraparietal sulcus, and the inferior frontal gyrus
      (IFG), bilaterally. The IFG and the visual areas were significantly more active
      in patients than controls. The between-group interaction analysis showed that in
      patients with MS, part of the regions of the MNS were more active also during the
      simple task. CONCLUSIONS: This study suggests increased activation of the mirror
      neuron system in patients with multiple sclerosis (MS) with a normal level of
      function and widespread CNS damage. The potentialities of this system in
      facilitating clinical recovery in patients with MS and other neurologic
      conditions should be investigated.

PMID- 18077799
TI  - Nitrosative stress with HIV dementia causes decreased L-prostaglandin D synthase
      activity.
AB  - BACKGROUND: The prevalence of HIV-associated neurocognitive disorders is
      increasing as HIV-infected individuals are living longer. The clinical
      manifestations of the syndrome also continue to evolve under the influence of
      antiretroviral drugs and comorbidities such as drugs of abuse. However, there are
      no surrogate markers for the disease, either to identify it de novo or to track
      its progression, and there is no proven treatment with the exception of
      antiretroviral drugs. METHODS: Levels of nitric oxide, nitrate, and 3
      nitrotyrosine (3-NT)-modified proteins were measured in the CSF of 46 patients
      with HIV infection stratified according to their neurocognitive status and
      history of IV drug use (IVD). The 3-NT-modified proteins were isolated and
      identified by tandem mass spectrometry, and the functional consequence of 3-NT
      modification of L-prostaglandin D synthase (L-PGDS), the most abundant protein,
      was determined. RESULTS: 3-NT-modified proteins were significantly elevated in
      patients with HIV infection who had progressive neurocognitive decline over the
      next 6 months and in patients with a history of IVD. Thirteen different proteins
      with 3-NT modification were identified in the CSF of these patients. L-PGDS was
      the most abundant. 3-NT modification of this protein resulted in loss of its
      enzymatic activity. CONCLUSIONS: There is increased nitrosative stress in CSF of
      HIV-infected patients with active dementia and in patients with a history of IV
      drug use, measurement of which may serve as a surrogate marker for these
      patients. Nitrosative stress may also have important functional consequences and
      may impact the pathogenesis of HIV-associated neurocognitive disorders.

PMID- 18077800
TI  - Patients with MCI and N400 or P600 abnormalities are at very high risk for
      conversion to dementia.
AB  - OBJECTIVE: We sought cognitive event-related potential (ERP) biomarkers of
      disease progression and subsequent conversion to dementia in mild cognitive
      impairment (MCI). BACKGROUND: Two ERP components, the P600 and N400, are
      sensitive to abnormal episodic/declarative memory and semantic processing. When
      congruous category-exemplars are repeated, smaller P600s (relative to initial
      presentation) are normally elicited. Repetitions of semantically incongruous
      words yield smaller N400 amplitude. In mild Alzheimer disease (AD), abnormalities
      of both the N400 and P600 repetition effects are present, suggesting a widespread
      failure of synaptic plasticity. METHODS: Patients with amnestic MCI (n = 32) were
      longitudinally studied annually with an ERP paradigm in which semantically
      congruous (50%) and incongruous target words are repeated 10 to 140 seconds after
      initial presentation. ERP data were analyzed to contrast MCI-to-AD converters
      (within 3 years) vs nonconverters, using split-plot analyses of variance.
      RESULTS: A statistically significant P600 congruous word repetition effect was
      found only in the nonconverter group (F = 9.9, p = 0.005 vs MCI converters). This
      effect correlated with verbal memory measures. Repetition of incongruous words
      produced a significant N400 amplitude attenuation (across right-hemisphere sites)
      in nonconverters, but not in converters. Patients with MCI with abnormal/reduced
      N400 or P600 word repetition effects had an 87 to 88% likelihood of dementia
      within 3 years while those with normal/spared N400 and P600 repetition effects
      had only an 11 to 27% likelihood. CONCLUSIONS: Abnormalities of the P600 or N400
      in mild cognitive impairment are associated with an increased risk of subsequent
      conversion to Alzheimer disease (AD). These event-related potential components
      may offer useful biomarkers for the detection and staging of very early AD.

PMID- 18077801
TI  - Effects of endothelin receptor type-A and type-B antagonists on prostaglandin
      F2alpha-induced luteolysis of the sheep corpus luteum.
AB  - Three experiments were designed to examine the mechanisms that govern
      prostaglandin (PGF2alpha)-induced regression of the sheep corpus luteum. Evidence
      is presented supporting the involvement of endothelin 1 (EDN1) in PGF2alpha
      induced luteolysis. Experiment 1 measured effects of PGF2alpha when actions of
      EDN1 were blocked by sustained administration of a type-A endothelin (EDNRA) or
      type-B endothelin (EDNRB) antagonist in vivo. Experiment 2 examined
      antisteroidogenic actions of PGF2alpha and EDN1 in the presence of an EDNRA or
      EDNRB antagonist in Day-8 luteal minces. In experiment 3, luteal cellular
      expression of EDNRA and EDNRB was determined immunohistochemically. Relative gene
      expression of EDNRA and EDNRB receptors was examined by real-time RT-PCR in Day-8
      sheep corpora lutea. EDNRA, but not EDNRB, participated in antisteroidogenic
      actions of EDN1. During the first 12 h after PGF2alpha-induced luteolysis, EDNRA
      antagonist did not prevent a decline in serum progesterone concentrations. Early
      actions of PGF2alpha are either direct or mediated by something other than EDN1.
      However, beyond 12 h after PGF2alpha, serum progesterone concentrations increased
      in EDNRA antagonist-treated animals until they were the same as saline-treated
      controls, whereas an EDNRB antagonist had no effect in vivo or in vitro. The
      EDNRA antagonist negated the antisteroidogenic actions of EDN1 but only partially
      abolished the actions of PGF2alpha in vitro. In contrast, the EDNRB antagonist
      was ineffective in abolishing antisteroidogenic actions of EDN1 and PGF2alpha.
      Whereas real-time RT-PCR demonstrated high expression of EDNRA and low expression
      of EDNRB, immunohistochemically, only EDNRA was located in small steroidogenic,
      endothelial, and smooth muscle cells. In summary, studies in ovine corpora lutea
      provided strong evidence that: 1) EDNRA, but not EDNRB, mediates
      antisteroidogenic actions of EDN1, 2) actions of PGF2alpha are both independent
      of and dependent upon mediation by EDN1, and 3) small steroidogenic cells are
      targets for antisteroidogenic effects of EDN1. Furthermore, the results from
      experiment 1 suggest that the intermediary role of EDN1 may be more important in
      later stages of luteal regression.

PMID- 18077802
TI  - Neonatal exposure to estradiol valerate programs ovarian sympathetic innervation
      and follicular development in the adult rat.
AB  - A single injection of estradiol valerate (EV) to 14-day-old rats (when the
      ovarian follicle population has been already established) disrupts cyclicity,
      increases the activity of key enzymes of androgen biosynthesis, and develops
      polycystic ovary by a causally related increase in ovarian noradrenaline (NA).
      The current study examined an early window of ovarian development to look for a
      specific stage of development at which estradiol can induce such changes in
      sympathetic activity and follicular development. A single dose of EV applied to
      rats before the first 12 h of life rapidly increases (after 24 h) the ovarian
      expression of nerve growth factor (Ngfb) and p75 low-affinity neurotrophic
      receptor (Ngfr) mRNAs. When adults, rats presented early vaginal opening,
      disrupted cyclicity, appearance of follicular cyst, absence of corpus luteum, and
      infertility. Total follicles decreased, mainly due to a reduced number of
      primordial follicles, suggesting that estradiol acts in the first stages of
      folliculogenesis, when primordial follicles are organizing. These changes
      paralleled a 6-fold increase in NA concentration. No changes in NA content were
      found in the celiac ganglia, suggesting a local, non-centrally mediated effect of
      estradiol. Surgical section of the superior ovarian nerve (the main source of
      sympathetic nerves to the ovary) to rats neonatally treated with EV decreased
      intraovarian NA, delayed vaginal opening, and blocked the development of
      follicular cyst and that of preovulatory follicles. Therefore, we can conclude
      that early exposure to estradiol permanently modifies ovarian sympathetic
      activity and causes profound changes in follicular development, leading to the
      polycystic ovary condition.

PMID- 18077803
TI  - Videos in clinical medicine. Central venous catheterization--subclavian vein.

PMID- 18077804
TI  - Images in clinical medicine. Dissecting aneurysm of the posterior cerebral
      artery.

PMID- 18077805
TI  - Going Dutch--managed-competition health insurance in the Netherlands.

PMID- 18077806
TI  - Dutch doctors and their patients--effects of health care reform in the
      Netherlands.

PMID- 18077807
TI  - Knock out, knock in, knock down--genetically manipulated mice and the Nobel
      Prize.

PMID- 18077808
TI  - Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis.
AB  - BACKGROUND: It is uncertain whether all adults with bacterial meningitis benefit
      from treatment with adjunctive dexamethasone. METHODS: We conducted a randomized,
      double-blind, placebo-controlled trial of dexamethasone in 435 patients over the
      age of 14 years who had suspected bacterial meningitis. The goal was to determine
      whether dexamethasone reduced the risk of death at 1 month and the risk of death
      or disability at 6 months. RESULTS: A total of 217 patients were assigned to the
      dexamethasone group, and 218 to the placebo group. Bacterial meningitis was
      confirmed in 300 patients (69.0%), probable meningitis was diagnosed in 123
      patients (28.3%), and an alternative diagnosis was made in 12 patients (2.8%). An
      intention-to-treat analysis of all the patients showed that dexamethasone was not
      associated with a significant reduction in the risk of death at 1 month (relative
      risk, 0.79; 95% confidence interval [CI], 0.45 to 1.39) or the risk of death or
      disability at 6 months (odds ratio, 0.74; 95% CI, 0.47 to 1.17). In patients with
      confirmed bacterial meningitis, however, there was a significant reduction in the
      risk of death at 1 month (relative risk, 0.43; 95% CI, 0.20 to 0.94) and in the
      risk of death or disability at 6 months (odds ratio, 0.56; 95% CI, 0.32 to 0.98).
      These effects were not found in patients with probable bacterial meningitis.
      Results of multivariate analysis indicated that dexamethasone treatment for
      patients with probable bacterial meningitis was significantly associated with an
      increased risk of death at 1 month, an observation that may be explained by cases
      of tuberculous meningitis in the treatment group. CONCLUSIONS: Dexamethasone does
      not improve the outcome in all adolescents and adults with suspected bacterial
      meningitis; a beneficial effect appears to be confined to patients with
      microbiologically proven disease, including those who have received prior
      treatment with antibiotics. (Current Controlled Trials number, ISRCTN42986828
      [controlled-trials.com] .).

PMID- 18077809
TI  - Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa.
AB  - BACKGROUND: In sub-Saharan Africa, bacterial meningitis is common and is
      associated with a high mortality. Adjuvant therapy with corticosteroids reduces
      mortality among adults in the developed world, but it has not been adequately
      tested in developing countries or in the context of advanced human
      immunodeficiency virus (HIV) infection. METHODS: We conducted a randomized,
      double-blind, placebo-controlled trial of dexamethasone (16 mg twice daily for 4
      days) and an open-label trial of intramuscular versus intravenous ceftriaxone (2
      g twice daily for 10 days) in adults with an admission diagnosis of bacterial
      meningitis in Blantyre, Malawi. The primary outcome was death at 40 days after
      randomization. RESULTS: A total of 465 patients, 90% of whom were HIV-positive,
      were randomly assigned to receive dexamethasone (233 patients) or placebo (232
      patients) plus intramuscular ceftriaxone (230 patients) or intravenous
      ceftriaxone (235 patients). There was no significant difference in mortality at
      40 days in the corticosteroid group (129 of 231 patients) as compared with the
      placebo group (120 of 228 patients) by intention-to-treat analysis (odds ratio,
      1.14; 95% confidence interval [CI], 0.79 to 1.64) or when the analysis was
      restricted to patients with proven pneumococcal meningitis (68 of 129 patients
      receiving corticosteroids vs. 72 of 143 patients receiving placebo) (odds ratio,
      1.10; 95% CI, 0.68 to 1.77). There were no significant differences between groups
      in the outcomes of disability and death combined, hearing impairment, and adverse
      events. There was no difference in mortality with intravenous ceftriaxone (121 of
      230 patients) as compared with intramuscular ceftriaxone (128 of 229 patients)
      (odds ratio, 0.88; 95% CI, 0.61 to 1.27). CONCLUSIONS: Adjuvant therapy with
      dexamethasone for bacterial meningitis in adults from an area with a high
      prevalence of HIV did not reduce mortality or morbidity. In this setting,
      intramuscular administration was not inferior to intravenous administration of
      ceftriaxone for bacterial meningitis. (Current Controlled Trials number,
      ISRCTN31371499 [controlled-trials.com].).

PMID- 18077810
TI  - Outcomes 18 months after the first human partial face transplantation.
AB  - BACKGROUND: We performed the first human partial face allograft on November 27,
      2005. Here we report outcomes up to 18 months after transplantation. METHODS: The
      postsurgical induction immunosuppression protocol included thymoglobulins
      combined with tacrolimus, mycophenolate mofetil, and prednisone. Donor
      hematopoietic stem cells were infused on postoperative days 4 and 11. Sequential
      biopsy specimens were taken from a sentinel skin graft, the facial skin, and the
      oral mucosa. Functional progress was assessed by tests of sensory and motor
      function performed monthly. Psychological support was provided before and after
      transplantation. RESULTS: Sensitivity to light touch, as assessed with the use of
      static monofilaments, and sensitivity to heat and cold had returned to normal at
      6 months after transplantation. Motor recovery was slower, and labial contact
      allowing complete mouth closure was achieved at 10 months. Psychological
      acceptance of the graft progressed as function improved. Rejection episodes
      occurred on days 18 and 214 after transplantation and were reversed. A decrease
      in inulin clearance led to a change in immunosuppressive regimen from tacrolimus
      to sirolimus at 14 months. Extracorporeal photochemotherapy was introduced at 10
      months to prevent recurrence of rejection. There have been no subsequent
      rejection episodes. At 18 months, the patient is satisfied with the aesthetic
      result. CONCLUSIONS: In this patient who underwent the first partial face
      transplantation, the functional and aesthetic results 18 months after
      transplantation are satisfactory.

PMID- 18077811
TI  - Clinical practice. Erectile dysfunction.

PMID- 18077812
TI  - Platelet activation and atherothrombosis.

PMID- 18077813
TI  - Images in clinical medicine. Occlusion and reperfusion of the middle cerebral
      artery.

PMID- 18077814
TI  - Case records of the Massachusetts General Hospital. Case 38-2007. A 44-year-old
      woman with generalized, painful, ulcerated skin lesions.

PMID- 18077815
TI  - Corticosteroids for acute bacterial meningitis.

PMID- 18077816
TI  - Rapid expansion of the health workforce in response to the HIV epidemic.

PMID- 18077817
TI  - Epoetin alfa in critically ill patients.

PMID- 18077818
TI  - Rheumatoid arthritis, systemic lupus erythematosus, and STAT4.

PMID- 18077819
TI  - Low-tidal-volume ventilation.

PMID- 18077820
TI  - The FDA and the IOM report.

PMID- 18077821
TI  - APOE Kyoto mutation in European Americans with lipoprotein glomerulopathy.

PMID- 18077823
TI  - Assessment of Chlamydia trachomatis, Ureaplasma urealyticum, Ureaplasma parvum,
      Mycoplasma hominis, and Mycoplasma genitalium in semen and first void urine
      specimens of asymptomatic male partners of infertile couples.
AB  - The purpose of this study was threefold: to compare semen and first void urine
      (FVU) specimens from asymptomatic infertile men for the detection of Chlamydia
      trachomatis, genital ureaplasma, and genital mycoplasma infections using in-house
      inhibitor-controlled polymerase chain reaction (PCR)-microtiter plate
      hybridization assay; to determine the prevalence of those organisms in infertile
      men in Tunisia; and to study the relationship between these bacteria and male
      infertility. Paired urine and semen specimens from 104 patients were examined by
      in-house PCR for the presence of DNA of Chlamydia trachomatis, genital
      ureaplasmas (Ureaplasma urealyticum and Ureaplasma parvum) and genital
      mycoplasmas (Mycoplasma hominis and Mycoplasma genitalium). Semen analysis was
      assessed according to the guidelines of the World Health Organization. Nominal
      scale variables, the Mann-Whitney test, and the Kruskal-Wallis nonparametric
      analysis of variance test were used for statistical analysis. There was a very
      high concordance (>95%) and a very good agreement (kappa > 0.9) between the
      detection of Chlamydia trachomatis, genital ureaplasmas, and Mycoplasma hominis
      in semen and corresponding FVU specimens. Our findings also show a high
      concordance (81.1%) and a good agreement (kappa = 0.79) between the detection of
      Mycoplasma genitalium in both specimens. C trachomatis, genital mycoplasmas, and
      genital ureaplasmas were found to be widespread among infertile male patients in
      Tunisia, as shown by their respective prevalences of 43.3%, 18.3%, and 14.4%. The
      mean values of seminal volume, sperm concentration, sperm viability, sperm
      motility, sperm morphology, and leukocyte count were not significantly related
      either to the detection of C trachomatis DNA or to that of genital ureaplasma or
      mycoplasma DNA in semen specimens. Using our in-house PCR, both semen and FVU
      were found to be sensitive diagnostic specimens for the detection of C
      trachomatis, ureaplasmas, and mycoplasmas. The FVU, a less invasive and self
      collected specimen, can serve as a marker for the presence of these organisms in
      the genital tract and can be used as a reliable way of detecting asymptomatic
      carriers of infection.

PMID- 18077822
TI  - Utility of magnetic cell separation as a molecular sperm preparation technique.
AB  - Assisted reproductive techniques (ARTs) have become the treatment of choice in
      many cases of infertility; however, the current success rates of these procedures
      remain suboptimal. Programmed cell death (apoptosis) most likely contributes to
      failed ART and to the decrease in sperm quality after cryopreservation. There is
      a likelihood that some sperm selected for ART will display features of apoptosis
      despite their normal appearance, which may be partially responsible for the low
      fertilization and implantation rates seen with ART. One of the features of
      apoptosis is the externalization of phosphatidylserine (PS) residues, which are
      normally present on the inner leaflet of the sperm plasma membrane. Colloidal
      superparamagnetic microbeads ( approximately 50 nm in diameter) conjugated with
      annexin V bind to PS and are used to separate dead and apoptotic spermatozoa by
      magnetic-activated cell sorting (MACS). Cells with externalized PS will bind to
      these microbeads, whereas nonapoptotic cells with intact membranes do not bind
      and could be used during ARTs. We have conducted a series of experiments to
      investigate whether the MACS technology could be used to improve ART outcomes.
      Our results clearly indicate that integrating MACS as a part of sperm preparation
      techniques will improve semen quality and cryosurvival rates by eliminating
      apoptotic sperm. Nonapoptotic spermatozoa prepared by MACS display higher quality
      in terms of routine sperm parameters and apoptosis markers. The higher sperm
      quality is represented by an increased oocyte penetration potential and
      cryosurvival rates. Thus, the selection of nonapoptotic spermatozoa by MACS
      should be considered to enhance ART success rates.

PMID- 18077824
TI  - Varicoceles: the diagnostic dilemma.
AB  - Clinical examination of the scrotum remains the most commonly used technique to
      diagnose varicoceles. However, scrotal anatomy (eg, thick scrotum, scarring,
      hydrocele) in some men may make physical examination alone unreliable. In these
      situations, imaging (eg, ultrasound, Doppler imaging, venography) may be used to
      diagnose a varicocele. The dilemma is that there are no widely accepted or used
      criteria to diagnose a varicocele based on imaging. This paper reviews the
      different imaging techniques used and the accuracy of each in diagnosing a
      varicocele.

PMID- 18077825
TI  - Mono-(2-ethylhexyl) phthalate increases spermatocyte mitochondrial peroxiredoxin
      3 and cyclooxygenase 2.
AB  - Mono-(2-ethylhexyl) phthalate (MEHP), the biologically active metabolite of the
      plasticizer di-(2-ethylhexyl) phthalate, is a member of a class of chemical
      compounds with known adverse effects on the male reproductive system. Recent
      studies showed that oxidative stress and mitochondrial dysfunction in germ cells
      may contribute to phthalate-induced disruption of spermatogenesis. To determine
      whether the redox-protein mitochondrial thioredoxin-dependent peroxidase,
      peroxiredoxin 3 (Prx3), may be a component of germ cell homeostasis mechanisms,
      this study first examined the physiologic relevance of Prx3 in the rodent testis
      by determining its cell-specific expression. Our findings show that prx3 mRNA is
      expressed in a developmental, cell-specific manner in rat Leydig cells, Sertoli
      cells, and germ cells; among mouse germ cells, prx3 expression was highest in
      spermatocytes, findings consistent with those in rat. In mouse meiotic
      spermatocytes, Prx3 was strikingly localized at the nuclear perimeter and
      cytoplasm, findings suggestive of a direct role for Prx3 in determining
      spermatocyte response to toxicants. To better define the mechanisms involved in
      male germ cell dysfunction following phthalate exposure, an immortalized mouse
      spermatocyte-derived germ cell line, GC-2spd(ts), was exposed to MEHP (24 hours;
      100 and 200 microM). We determined whether Prx3 and cyclooxygenase-2 (COX-2),
      pivotal proteins involved in oxidative stress responses in spatially restricted
      subcellular domains, were affected. Mitochondrial Prx3 and mitochondrial and
      cytosolic COX-2 significantly increased following 200 microM MEHP treatment;
      proliferation was inhibited without inducing cell death. Using this germ cell
      model, the data suggest that changes in cellular oxidation-reduction (redox)
      homeostasis in the germline can accompany MEHP exposure, disrupting mitochondrial
      antioxidant defenses, despite absence of phthalate-induced apoptosis.

PMID- 18077826
TI  - Nanomilled oral testosterone plus dutasteride effectively normalizes serum
      testosterone in normal men with induced hypogonadism.
AB  - Oral androgen development has been hampered by the rapid metabolism of orally
      administered testosterone (T) and low bioavailibility. The addition of the 5alpha
      reductase inhibitor dutasteride (D) to oral T in oil dramatically improves
      concentrations of serum T. In this study we evaluate the absorption of oral T+D,
      comparing nanomilled T (NmT+D) vs T dissolved in oil (Capmul; CpT+D), as
      nanomilling might offer a simpler, more practical means of oral T administration,
      given the limited solubility of T in oil. Twelve healthy men were administered
      leuprolide on Day -14 to suppress endogenous T biosynthesis and were pretreated
      with D to block 5alpha-reductase. Once hypogonadal, subjects were sequentially
      administered 200- and 400-mg doses of CpT+D and NmT+D in the fasted and fed
      states. Serum T and dihydrotestosterone (DHT) were measured: before dose and at
      0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after each dose. Two weeks after
      leuprolide administration, T levels were below the normal range. A 400-mg dose of
      either formulation of oral T+D increased mean serum T above the lower limit of
      the normal range for 8-10 hours. Food had a minimal effect on the pharmacokinetic
      parameters of the NmT+D formulation but decreased the maximum observed
      concentration after dosing (C(max)) for CpT+D. Serum DHT remained below the
      normal range throughout the study period with both formulations. No significant
      changes in liver function tests or other adverse events were observed. A 400-mg
      dose of either oral T+D formulation normalized serum T for 8-10 hours and
      suppressed DHT. NmT allows for tablet formulation, and its pharmacokinetics were
      not affected by food, demonstrating the feasibility of oral nanomilled T as a
      promising and practical twice-daily therapy for the treatment of male
      hypogonadism.

PMID- 18077828
TI  - Genetic variations and treatments that affect the lifespan of the NPC1 mouse.
AB  - Niemann-Pick type C (NPC) disease is a multisystem disorder caused primarily by a
      mutation in the npc1 gene. These studies evaluated the effect of genetic
      background, deletion of additional genes, and administration of several agents on
      the age at death in a murine model of this disorder. Such factors as differing
      strain background or genetic drift within a given background in the npc1(-/-)
      mouse significantly altered the age at death and the degree of organ disease.
      Genetic deletion of Siat9 (GM3 synthetase) or Nr1h2 [liver X receptor (LXR)beta]
      shortened the life of the npc1(-/-) animals. Daily treatment of the npc1(-/-)
      mice with an LXR agonist or administration of a single dose of cyclodextrin, with
      or without the neurosteroid allopregnanolone, significantly slowed
      neurodegeneration and increased the lifespan of these animals. These data
      illustrate that the age at death of the npc1(-/-) mouse can be significantly
      influenced by many factors, including differences in strain background, other
      inactivating gene mutations (Siat9 and lxrbeta), and administration of agents
      such as LXR agonists and, particularly, cyclodextrin. It is currently not clear
      which of these effects is nonspecific or which might relate directly to the
      molecular defect present in the NPC1 syndrome.

PMID- 18077829
TI  - Richard E. Peter (1943-2007).

PMID- 18077830
TI  - A rare cause of spontaneous pneumothorax after lifesaving pneumonectomy in a
      patient with sarcoidosis.

PMID- 18077827
TI  - Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes.
AB  - In this article, the formation of prokaryotic and eukaryotic cardiolipin is
      reviewed in light of its biological function. I begin with a detailed account of
      the structure of cardiolipin, its stereochemistry, and the resulting physical
      properties, and I present structural analogs of cardiolipin that occur in some
      organisms. Then I continue to discuss i) the de novo formation of cardiolipin,
      ii) its acyl remodeling, iii) the assembly of cardiolipin into biological
      membranes, and iv) the degradation of cardiolipin, which may be involved in
      apoptosis and mitochondrial fusion. Thus, this article covers the entire
      metabolic cycle of this unique phospholipid. It is shown that mitochondria
      produce cardiolipin species with a high degree of structural uniformity and
      molecular symmetry, among which there is often a dominant form with four
      identical acyl chains. The subsequent assembly of cardiolipin into functional
      membranes is largely unknown, but the analysis of crystal structures of membrane
      proteins has revealed a first glimpse into the underlying principles of
      cardiolipin-protein interactions. Disturbances of cardiolipin metabolism are
      crucial in the pathophysiology of human Barth syndrome and perhaps also play a
      role in diabetes and ischemic heart disease.

PMID- 18077831
TI  - Routine HIV screening in the emergency department using the new US Centers for
      Disease Control and Prevention Guidelines: results from a high-prevalence area.
AB  - BACKGROUND: In 2006, the US Centers for Disease Control and Prevention (CDC)
      released new recommendations for routine HIV testing. Among these were
      recommendations that emergency departments (EDs) offer routine opt-out HIV
      screening to their patients. We established a screening program implementing
      these recommendations at an urban university hospital ED in Washington, DC. We
      report the results of this program. METHODS: During a 3-month period, ED patients
      being treated for a wide range of conditions were approached by trained HIV
      screeners and offered point-of-care rapid HIV testing. Patients with positive
      results were referred to hospital or community resources for confirmatory testing
      and treatment. RESULTS: During the program period, 14,986 patients were treated
      in the ED and 4151 (27.6%) were offered HIV screening. The mean patient age was
      37.5 years; 48.5% were black, 39.0% were non-Hispanic white, 4.1% were Hispanic,
      1.7% were Asian, and 6.7% responded as being other race. A total of 56.1% were
      female, and most lived within the Washington, DC metropolitan area. Of the
      patients offered HIV screening, 2476 (59.7%) accepted the test. Of the 26
      patients with a preliminary positive screen, 13 were lost to follow-up, 9 were
      confirmed positive by Western blot, and 4 were confirmed negative by Western
      blot. Eight of the 9 patients with confirmed HIV infection were successfully
      linked to follow-up care. CONCLUSIONS: The implementation of the CDC
      recommendations establishing routine opt-out HIV screening programs in EDs is
      feasible. Further efforts to establish routine ED HIV testing are therefore
      warranted.

PMID- 18077832
TI  - Optimizing measurement of self-reported adherence with the ACTG Adherence
      Questionnaire: a cross-protocol analysis.
AB  - BACKGROUND/OBJECTIVE: The AIDS Clinical Trials Group (ACTG) Adherence
      Questionnaire is used extensively, but investigators frequently only use the
      first item of the questionnaire (4-day recall). DESIGN/METHODS: A secondary
      analysis was conducted to (1) estimate the validity and reliability of each of
      the 5 scale items and (2) compare the approach commonly used to summarize
      adherence data collected with the instrument (average 4-day recall) with
      alternate approaches derived using principal component (PC) analysis and the full
      questionnaire. We hypothesized that an estimate of adherence taking all items of
      the questionnaire into account would provide a stronger measure of adherence.
      RESULTS: Logistic regression analyses showed that the first PC identified (PC1)
      was significantly correlated with plasma HIV RNA outcome (P < 0.0001 for ACTG 370
      data and P = 0.006 for ACTG 398 data) and correlated with plasma HIV RNA better
      than average 4-day recall. An adherence index formulated using weights of PC1
      showed substantially greater variability in the range of adherence scores in
      comparison to average 4-day adherence recall alone. PC1 compared favorably with 2
      indices derived from medication event monitoring system data as well.
      CONCLUSIONS: Findings indicate that a superior assessment of antiretroviral
      adherence may be obtained with the ACTG Adherence Questionnaire by using the
      method employed in this analysis.

PMID- 18077833
TI  - Motivational interviewing and cognitive-behavioral intervention to improve HIV
      medication adherence among hazardous drinkers: a randomized controlled trial.
AB  - OBJECTIVE: To assess the efficacy of a behavioral intervention designed to
      improve HIV medication adherence and reduce alcohol consumption among HIV
      positive men and women. DESIGN: A randomized controlled trial conducted between
      July 2002 and August 2005. SETTING: A behavioral research center in New York
      City. PARTICIPANTS: HIV-positive men and women (n = 143) who were on HIV
      antiretroviral medication and met criteria for hazardous drinking. INTERVENTION:
      Participants were randomly assigned to an 8-session intervention based on
      motivational interviewing and cognitive-behavioral skills building or a time- and
      content-equivalent educational condition. OUTCOME MEASURES: Viral load, CD4 cell
      count, and self-reported adherence and drinking behavior were assessed at
      baseline and at 3- and 6-month follow-ups. RESULTS: Relative to the education
      condition, participants in the intervention demonstrated significant decreases in
      viral load and increases in CD4 cell count at the 3-month follow-up and
      significantly greater improvement in percent dose adherence and percent day
      adherence. There were no significant intervention effects for alcohol use,
      however, and effects on viral load, CD4 cell count, and adherence were not
      sustained at 6 months. CONCLUSIONS: An 8-session behavioral intervention can
      result in improvement in self-report and biologic markers of treatment adherence
      and disease progression. This type of intervention should be considered for
      dissemination and integration into HIV clinics providing comprehensive care for
      HIV-positive persons with alcohol problems. Although the effect was attenuated
      over time, future studies might test the added effectiveness of booster sessions
      or ongoing adherence counseling.

PMID- 18077834
TI  - Metabolic function and the prevalence of lipodystrophy in a population of HIV
      infected African subjects receiving highly active antiretroviral therapy.
AB  - OBJECTIVE: This study measured the prevalence of lipodystrophy and the metabolic
      effects of highly active antiretroviral therapy (HAART) in HIV-infected African
      subjects. METHODS: Prevalence was measured in 571 Rwandans receiving HAART for >
      or = 6 months. Metabolic variables were measured in 100 HIV-positive adults with
      lipodystrophy, 50 HIV-positive nonlipodystrophic adults, and 50 HIV-negative
      controls. RESULTS: A HAART regimen of stavudine, lamivudine, and nevirapine was
      used by 81.6% of subjects; none received protease inhibitors. Lipodystrophy was
      observed in 34% (48.5% in urban groups and 17.3% in rural groups) of subjects,
      with a prevalence of 69.6% in those receiving HAART for >72 weeks. Peripheral
      lipoatrophy combined with abdominal lipohypertrophy was observed in 72% of
      lipodystrophic subjects. HIV-positive adults with lipodystrophy had a
      significantly higher waist-to-hip ratio (WHR; 0.99 +/- 0.05 vs. 0.84 +/- 0.03: P
      < 0.0005) than HIV-positive nonlipodystrophic adults. Total cholesterol
      concentrations (median [interquartile range], mmol/L) were significantly higher
      in the HIV-positive adults with lipodystrophy (3.60 [1.38]) than in HIV-positive
      nonlipodystrophic adults (3.19 [0.65]; P < 0.005) and control (3.13 [0.70]; P <
      0.0005) groups. Impaired fasting glucose was observed in 18% of HIV-positive
      adults with lipodystrophy, 16% of HIV-positive nonlipodystrophic adults, and 2%
      of controls, but insulin levels did not differ. CONCLUSIONS: African subjects
      with lipodystrophy have increased WHR, glucose, and cholesterol levels. Glucose
      concentrations are also elevated in nonlipodystrophic HIV-positive subjects.
      Therefore, factors other than body fat redistribution contribute to the glucose
      intolerance.

PMID- 18077835
TI  - Immune reconstitution inflammatory syndrome: risk factors and treatment
      implications.
AB  - BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS), also called
      immune restoration disease, occurs in a subset of HIV-infected patients after the
      initiation of highly active antiretroviral therapy (HAART) and can be
      diagnostically challenging and difficult to treat. We sought to determine
      clinical risk factors for the development of IRIS. METHODS: Patients from the
      Johns Hopkins HIV Clinic who had IRIS were identified and matched with 4 controls
      without IRIS who had initiated HAART within 6 months of the case. RESULTS: Forty
      nine cases of IRIS were identified; patients presented a median of 29 days from
      the initiation of HAART (range: 4 to 186 days). A multivariate analysis showed
      that the development of IRIS was independently associated with using a boosted
      protease inhibitor (BPI) (odds ratio [OR] = 7.41; P = 0.006), a nadir CD4 count
      <100 cells/mm(3) (OR = 6.2; P < 0.001), and a plasma HIV viral RNA decrease of
      more than 2.5 log at the time of IRIS compared with RNA levels before the
      initiation of HAART. Incrementally greater decreases in viral loads directly
      correlated with increased risk for the development of IRIS. CONCLUSIONS: The most
      immunosuppressed patients treated with the most potent regimens, particularly BPI
      based regimens, resulting in significant HIV viral load declines are at greatest
      risk for the development of IRIS after HAART initiation.

PMID- 18077837
TI  - HIV partner notification outcomes for HIV-infected patients by duration of
      infection, San Francisco, 2004 to 2006.
AB  - BACKGROUND: The San Francisco Department of Public Health conducts HIV third
      party partner notification in the following populations based on standard Centers
      for Disease Control and Prevention (CDC) guidelines: (1) persons with acute and
      nonacute incident HIV infection tested at the municipal sexually transmitted
      disease (STD) clinic and the county hospital and (2) all county residents with
      early syphilis and long-standing HIV infection. METHODS: We reviewed routinely
      collected demographic and partner notification outcome data among acute and
      nonacute cases between 2004 and 2006 and among long-standing cases between July
      2005 and December 2006. Outcomes were examined among the 3 case types. RESULTS:
      Most acute (n = 30), nonacute (n = 398), and long-standing cases (n = 335)
      occurred in gay/bisexual men (89%), and most case-patients were interviewed
      (80%). In acute and nonacute cases, 13% of partners tested for HIV were newly
      identified as HIV-infected. The number of patients interviewed per new HIV
      infection identified was 25 for acute cases, 21 for nonacute cases, and 39 for
      long-standing cases; however, half of recent new HIV infections were identified
      among partners of long-standing patients. Few patients or partners refused
      partner notification services. CONCLUSIONS: Partner notification was acceptable
      and successfully identified new HIV infections. Other jurisdictions should
      consider implementing or expanding partner notification for HIV infection. More
      evaluation is needed of the effectiveness of partner notification among HIV
      infected persons with other STDs.

PMID- 18077836
TI  - The cost-effectiveness of antiretroviral therapy for treating HIV disease in the
      Caribbean.
AB  - BACKGROUND: Antiretroviral therapy (ART) recently became available in the
      Organization of Eastern Caribbean States (OECS). Survival benefits and budgetary
      implications associated with universal access to ART have not been examined in
      the Caribbean. METHODS: Using a state-transition simulation model of HIV with
      regional data, we projected survival, cost, and cost-effectiveness of treating an
      HIV-infected cohort. We examined 1 or 2 ART regimens and cotrimoxazole. In
      sensitivity analysis, we varied HIV natural history and ART efficacy, cost, and
      switching criteria. RESULTS: Without treatment, mean survival was 2.30 years
      (mean baseline CD4 count = 288 cells/microL). One ART regimen with cotrimoxazole
      when the CD4 count was <350 cells/microL provided an additional 5.86 years of
      survival benefit compared with no treatment; the incremental cost-effectiveness
      ratio was $690 per year of life saved (YLS). A second regimen added 1.04 years of
      survival benefit; the incremental cost-effectiveness ratio was $10,960 per YLS
      compared with 1 regimen. Results were highly dependent on second-line ART costs.
      Per-person lifetime costs decreased from $17,020 to $9290 if second-line ART
      costs decreased to those available internationally, yielding approximately $8
      million total savings. CONCLUSIONS: In the OECS, ART is cost-effective by
      international standards. Reducing second-line ART costs increases cost
      effectiveness and affordability. Current funding supports implementing universal
      access regionally over the next year, but additional funding is required to
      sustain lifetime care for currently infected persons.

PMID- 18077838
TI  - Independent effects of nevirapine prophylaxis and HIV-1 RNA suppression in breast
      milk on early perinatal HIV-1 transmission.
AB  - BACKGROUND: The mechanism of action of single-dose nevirapine on reducing mother
      to-child transmission of HIV-1 may involve reduction of maternal HIV-1 or
      prophylaxis of infants. METHODS: In a study that randomized pregnant mothers to
      HIVNET 012 nevirapine versus short-course antenatal zidovudine, we compared
      breast milk HIV-1 RNA viral shedding and administration of single-dose nevirapine
      between mothers who transmitted HIV-1 to their infants at 6 weeks postpartum and
      those who did not. RESULTS: In multivariate analyses, maximum breast milk HIV-1
      RNA levels (hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.25 to 4.99;
      P = 0.01) and nevirapine use (HR = 0.12, 95% CI: 0.02 to 0.97; P = 0.05) were
      each independently associated with perinatal transmission at 6 weeks postpartum.
      Mothers who transmitted HIV-1 to their infants had significantly higher HIV-1 RNA
      levels in their breast milk between the second day and sixth week postpartum.
      Among mothers with maximum breast milk virus levels less than a median of 3.5
      log(10) copies/mL, the administration of nevirapine further decreased HIV-1
      transmission risk from 22.2% to 0.0% (P = 0.04). CONCLUSIONS: Peripartum
      administration of single-dose nevirapine to mother and infant decreases early
      perinatal HIV-1 transmission by means of breast milk HIV-1 RNA suppression and,
      independently, by providing the infant with exposure prophylaxis.

PMID- 18077839
TI  - Men who have sex with men: estimated population sizes and mortality rates by
      race/ethnicity, Miami-Dade County, Florida.
AB  - BACKGROUND: Estimated numbers of men who have sex with men (MSM) by
      race/ethnicity and mortality rates among such MSM with HIV/AIDS are unavailable.
      This hampers efficient targeting of HIV/AIDS prevention and care resources.
      METHODS: An existing estimation methodology was adapted to develop MSM population
      estimates by race/ethnicity for Miami-Dade County, Florida. We ascertained and
      characterized deaths that occurred during 2003 to 2005 among MSM HIV/AIDS cases,
      matching HIV/AIDS surveillance and vital statistics registries. We calculated
      estimated average annual racial/ethnic-specific mortality rates and rate ratios
      (RRs) among MSM HIV/AIDS cases. RESULTS: An estimated 63,020 men aged > or =18
      years in the county are MSM (7.5% of all men aged > or =18 years; point
      estimate). Among 754 MSM HIV/AIDS deaths, point-estimate mortality rates per
      100,000 MSM were higher for blacks (733.5) than for whites (229.2) (P < 0.01) and
      Hispanics (360.5) (P < 0.01). The best estimate of the black/white MSM mortality
      RR among HIV/AIDS cases was 3.20:1 (P < 0.01); for Hispanic/white MSM, it was
      1.57:1 (P < 0.01). Sensitivity analyses suggested the estimates were reasonably
      robust to biases that we examined. CONCLUSIONS: Black and Hispanic MSM were more
      likely to die with HIV/AIDS than white MSM. Plausible racial/ethnic-specific MSM
      population and mortality rate estimates can inform effective HIV/AIDS prevention
      efforts and program planning.

PMID- 18077840
TI  - HIV rates and risk behaviors are low in the general population of men in Southern
      India but high in alcohol venues: results from 2 probability surveys.
AB  - BACKGROUND: As the HIV epidemic continues to expand in India, empiric data are
      needed to determine the course of the epidemic for high-risk populations and the
      general population. METHODS: Two probability surveys were conducted in Chennai
      slums among a household sample of men and alcohol venue patrons ("wine shops") to
      compare HIV and other sexually transmitted disease (STD) prevalence and to
      identify STD behavioral risk factors. RESULTS: The wine shop sample (n = 654) had
      higher rates of HIV and prevalent STDs (HIV, herpes simplex virus 2 [HSV-2],
      syphilis, gonorrhea, or chlamydia) compared with the household sample (n = 685)
      (3.4% vs. 1.2%, P = 0.007 and 21.6% vs. 11.8%, P < 0.0001, respectively). High
      risk behaviors in the household sample was rare (<4%), but 69.6% of wine shop
      patrons had >2 partners, 58.4% had unprotected sex with a casual partner, and
      54.1% had exchanged sex for money in the past 3 months. A multivariate model
      found that older age, ever being married, ever being tested for HIV, and having
      unprotected sex in the past 3 months were associated with STD prevalence in wine
      shop patrons. CONCLUSIONS: Prevalent HIV and STDs, and sexual risk behaviors are
      relatively low among the general population of men. We found that men who
      frequent alcohol venues practice high-risk behaviors and have high rates of STDs,
      including HIV, and may play an important role in expanding the Indian epidemic.

PMID- 18077841
TI  - Elevated iron status strongly predicts mortality in West African adults with HIV
      infection.
AB  - OBJECTIVE: To comprehensively assess iron status and determine whether elevated
      iron status, like anemia, predicts mortality. METHODS: We followed 1362 Gambian
      adults (53% female) in an HIV-seroprevalent clinic-based cohort over 11.5 years
      to ascertain all-cause mortality. Baseline iron status (iron, soluble transferrin
      receptor [sTfR], transferrin, ferritin, transferrin saturation, log [transferrin
      receptor: ferritin]), age, gender, ethnicity, hemoglobin, body mass index, HIV
      type, absolute CD4 count, malaria status, and [alpha]-(1)-antichymotrypsin were
      measured. RESULTS: The mortality rate was 25.9/100 person-years. Elevated iron
      universally predicted greater mortality compared to normal iron status for all
      iron status indices, with the exception of sTfR in unadjusted models. In fully
      adjusted models, transferrin (elevated vs. normal, hazard ratio [HR]: 1.77; 95%
      confidence interval [CI]: 1.30 to 2.42; P < 0.001), ferritin (elevated vs.
      normal, HR: 1.40; 95% CI: 1.07 to 1.83; P = 0.014), and the combined iron status
      index (highly elevated vs. normal, HR: 2.20; 95% CI: 1.16 to 4.18; P = 0.016)
      remained significant predictors. As expected, hemoglobin (Hb) concentration and
      absolute CD4 counts were each inversely associated with mortality. CONCLUSIONS:
      Elevated iron status predicts mortality in HIV infection, even after adjustment
      for immunosuppression and other confounders. This finding has implications in the
      clinical monitoring of disease progression and for iron-supplementation practices
      in areas of high HIV prevalence.

PMID- 18077842
TI  - LMNA messenger RNA expression in highly active antiretroviral therapy-treated HIV
      positive patients.
AB  - The LMNA gene encodes for lamins A and C as major products, which are involved in
      nuclear stability, chromatin structure, and gene expression. Several LMNA
      mutations cause an insulin-resistant lipodystrophy that shares features with HIV
      related lipodystrophy. Some HIV-treatment agents alter lamin A/C maturation,
      organization, and stability in 3T3-L1. We aimed to test the hypothesis that human
      adipose tissue LMNA expression can be altered in highly active antiretroviral
      therapy (HAART)-treated HIV-positive patients with lipodystrophy. We have also
      analyzed both isoforms and explored if their expression is associated with
      insulin resistance or inflammation in these patients. A cross-sectional study
      that analyzed abdominal subcutaneous adipose tissue from 39 treated HIV-positive
      patients (25 of whom had lipodystrophy) and 21 uninfected control subjects was
      performed. We have observed lower levels of lamin A isoform but normal levels of
      lamin C isoform in all HIV-infected patients, irrespective of the presence or
      absence of lipodystrophy, which reinforces the idea that an altered lamin A/C
      ratio could reflect a pathogenic condition. We have also found a correlation
      between LMNA adipose expression and several cytokine and adipogenic gene markers
      in HIV-positive patients, regardless of the presence or absence of lipodystrophy.
      Hence, in the present study, the lower lamin A expression observed in HIV
      positive patients is related to HIV itself or to treatments rather than to the
      presence of lipodystrophy.

PMID- 18077843
TI  - Trends in evaluation for sexually transmitted infections among HIV-infected
      people, King County, Washington.
AB  - OBJECTIVE: To assess clinician sexual risk assessment and sexually transmitted
      infection (STI) screening rates in a large cohort of human immunodeficiency virus
      (HIV)-infected patients in King County, Washington. METHODS: We abstracted data
      from medical records of HIV-infected patients seen in diverse clinical settings
      during 2000-2003 and used [chi]2 and logistic regression to identify factors
      associated with higher rates of sexual risk assessment and STI testing. We
      defined patients as having had a sexual risk or STI assessment if the medical
      record included any information about the patient's recent sexual behavior or
      included laboratory test results for gonorrhea, chlamydial infection, syphilis,
      or trichomoniasis. RESULTS: The proportion of patients with any recorded risk
      assessment or STI testing increased from 16% in 2000 to 46% in 2001, and
      thereafter remained stable. On multivariate analysis, having a sexual risk or STI
      evaluation was significantly associated with later time period of evaluation,
      receiving care in a HIV specialty clinic, higher number of outpatient visits,
      being men who have sex with men, Seattle residence (vs. residence outside
      Seattle), female gender, higher CD4 count, white race, and having never received
      antiretroviral therapy. CONCLUSION: Although sexual risk and STI evaluation rates
      increased from 2000 to 2001, they now appear to be stable and many patients,
      particularly those seen outside of HIV specialty clinics, are not routinely
      evaluated for ongoing risks or STI. Clinicians and public health authorities need
      to develop better mechanisms to assure recommended risk assessments and STI
      testing among persons with HIV.

PMID- 18077844
TI  - Education attainment and the risk of HIV-1 infections in rural Kilimanjaro Region
      of Tanzania, 1991-2005: a reversed association.
AB  - OBJECTIVE: Previous studies found educated individuals to have higher risk of
      human immunodeficiency virus (HIV)-1 infection in Africa. A reverse in this
      association was predicted. We investigated the change in this association from
      1991 to 2005 in a rural population in Tanzania. STUDY DESIGN: Two cross-sectional
      surveys were conducted in 1991(N = 1,152, response rate 76.4%) and 2005 (N =
      1,528, 73.0%). Consenting individuals aged 15 to 44 years living in Oria village
      were interviewed and gave blood for HIV-1 testing. RESULTS: Primary [adjusted
      odds ratio (AOR), 2.7; 95% confidence interval (CI): 1.3-20.0] and
      secondary/higher education (AOR, 4.5; 95% CI: 1.4-24.9) were associated with
      increased risk of HIV-1 infection in 1991. A reversed association was observed in
      2005 where reduced odds of infection were associated with primary (AOR, 0.5; 95%
      CI: 0.2-0.8) and secondary/higher education (AOR, 0.4; 95% CI: 0.3-0.9). This was
      most pronounced among educated men. Corresponding reduction in risk behaviors
      were observed. Increased odds of reporting ever use of condom (AOR, 2.8; 95% CI:
      1.1-7.3) and 70% reduction in reporting >or=2 sexual partners in the past year
      was observed among educated women. Educated men reported 60% reduction in the
      odds of reporting >or=2 sexual partners in the past month preceding the last
      survey. CONCLUSIONS: A reversed association between education attainment and HIV
      1 infection was observed in this population between 1991 and 2005. Education
      seems to have an empowering role in women. Decreased risk among educated men may
      have an impact on HIV-1 transmission. Improving education sector in rural areas
      might be instrumental in the fight against the HIV epidemic.

PMID- 18077845
TI  - Longitudinal association between hormonal contraceptives and bacterial vaginosis
      in women of reproductive age.
AB  - OBJECTIVES: This study examined whether hormonal contraceptive use is associated
      with diagnosis of bacterial vaginosis (BV) over 1 year. STUDY DESIGN: A total of
      3,077 women of reproductive age were recruited from gynecologic and family
      planning clinics for a 1-year prospective longitudinal study. Data collected over
      5 visits included demographics, health and hygiene behaviors, and gynecological
      exams. Gram stains were used to quantify vaginal flora. RESULTS: There was a
      decreased risk of overall BV prevalence among oral contraceptive users (odds
      ratio, OR 0.76; confidence interval, CI 0.63-0.90) and among those using hormonal
      injection/implant (OR 0.64; CI 0.53-0.76). An increased risk for BV prevalence
      (OR 1.38; CI 1.11-1.71) and incidence (OR 1.43; 1.02-2.07) was observed among
      those subjects who had tubal ligation. Greater remission of BV was found among
      those using hormonal injection or implant (OR 1.67; CI 1.23-2.27) whereas less
      remission occurred among those subjects who had tubal ligation (OR 0.56; CI 0.39
      0.80). CONCLUSIONS: Hormonal contraceptive use is associated with a decreased
      risk of BV.

PMID- 18077846
TI  - Tacrolimus ointment-induced relapse of schizophrenia: a case report.

PMID- 18077847
TI  - Cost-effectiveness of alternative outpatient pelvic inflammatory disease
      treatment strategies.
AB  - OBJECTIVE: Effectiveness differences between outpatient pelvic inflammatory
      disease (PID) treatment regimens are uncertain, but significant differences in
      cost exist. GOAL: To examine the influence of antibiotic costs on PID therapy
      cost-effectiveness. STUDY DESIGN: The authors used a Markov decision model to
      estimate the cost-effectiveness of recommended antibiotic regimens for PID and
      performed a value of information analysis to guide future research. RESULTS:
      Antibiotic costs vary between USD 43 and USD188. Pairwise comparisons, assuming a
      hypothetical 1% relative risk reduction in PID complications with the more
      expensive regimen, showed economically reasonable cost-effectiveness ratios.
      Value of information and sample size considerations support further investigation
      to detect 10% PID complication rate differences between regimens with >or=USD 50
      cost differences. CONCLUSIONS: Within the cost range of recommended regimens, use
      of more expensive antibiotics would be economically reasonable if relatively
      small decreases in PID complication rates exist. Further investigation of
      effectiveness differences between regimens is needed.

PMID- 18077848
TI  - Opa typing of Neisseria gonorrhoeae strains isolated from patients attending
      sexually transmitted disease clinics in China.
AB  - BACKGROUND: Gonorrhoea has been one of the most common sexually transmitted
      diseases (STDs) in China. A clear understanding of its transmission dynamics is
      important in formulating prevention and control measures. GOAL: To investigate
      the distribution of opa types in patients attending at STD clinics in China and
      to evaluate the concordance between epidemiologic data and opa-typing results.
      STUDY DESIGN: Opa typing was conducted for 330 Neisseria gonorrhoeae strains
      isolated from the patients at 4 STDs clinics in China, and the epidemiologic data
      were collected as well. RESULTS: A total of 309 opa types were detected from the
      330 isolates. Two hundred ninety-two opa types were unique, and 17 opa types were
      found in more than 1 patient. Opa typing confirmed all 9 sexual links that were
      revealed by epidemiologic information and further identified 9 opa clusters and 8
      similar pairs. CONCLUSIONS: Opa typing is a discriminatory tool that can be used
      in epidemiologic studies on gonococcal infections. This technique is more
      powerful than epidemiologic data to identify sexual links and improve our
      understanding of the transmission dynamics of gonorrhoea.

PMID- 18077849
TI  - Human Papillomavirus infections in Cuban women with cervical intraepithelial
      neoplasia.

PMID- 18077850
TI  - Wal-Mart not discounting health. Retail giant partnering with hospitals to boost
      clinics.

PMID- 18077852
TI  - Quality better, not great. Compliance still low: Joint Commission report.

PMID- 18077851
TI  - FCC has IT dreams in rural setting. Commissioner talks $400 million for
      telehealth.

PMID- 18077853
TI  - Profit dips a bit. Joint Commission sees revenue, expenses rise slightly.

PMID- 18077854
TI  - Rewarding investments. CHA sees higher returns than expected in 2006, Form 990
      shows.

PMID- 18077855
TI  - Spending, expenses up at AMA. Revenue dropped 3.3% for fiscal 2006.

PMID- 18077856
TI  - Net income plunges at FAH. Adjustment to expense accruals explains drop on 990s.

PMID- 18077857
TI  - Quality-costs=access. A remade health system is key to universal coverage.

PMID- 18077858
TI  - By the numbers. A strong pulse. Thomson's 100 top hospitals: cardiovascular
      benchmarks for success.

PMID- 18077859
TI  - [Early embryo death: does the male factor play a role?].
AB  - OBJECTIVE: To discuss the possible role of the male factor in early embryo death.
      METHOD: A detailed bibliographic review has been put together to establish which
      alterations in spermatozoa can be associated with early embryo death. RESULTS:
      Before the fusion between plasma membranes of the sperm and the oocyte occurs,
      both germ cells must undergo a maturation process that allows successful
      fertilization and embryo development. The study of couples with early embryo loss
      is usually approached from the side of the woman due to the obvious relationship
      that exists between the female and the developing embryo. However, it is not
      illogical to suppose that a genetic or epigenetic alteration of the sperm could
      have important consequences on these losses due to the necessary contribution of
      the male gamete not only to embryonic but also to placental development. On the
      other hand, spermatozoa have certain characteristics such as a highly compact
      DNA, they undergo apoptosis and the seminal plasma contains antioxidants that
      protect the structural and functional integrity of the germ cell. These factors
      assure fertilization and embryo development. Nevertheless, epigenetic alterations
      of the sperm such as altered chromatin packing, mistakes in imprinting, absence
      or alteration of the centrosome, telomeric shortening and absence of sperm RNA,
      could affect functions leading to early embryo loss. CONCLUSIONS: Knowledge
      concerning sperm intervention previous to embryo development will provide the
      basis for better understanding and for possible diagnosis and treatment of
      diverse reproductive alterations in men that could impede embryo development.

PMID- 18077860
TI  - [Histomorphometric findings in the residual prostate and prostatic hollow after
      retropubic surgery for BPH: (I) baseline data obtained from the last 70
      consecutive cases].
AB  - OBJECTIVES: To present the data obtained from surgical specimens and biopsies of
      residual prostate and prostatic capsule, which in addition to the information
      provided by imaging tests give us the baseline situation of the prostatic
      surgical bed and residual prostate after transcervical hemostatic adenomectomy
      with capsule plasty. All this is the first step for the long-term study of its
      evolution and possible implications in the genesis of new obstructive or
      neoplastic pathology. METHODS: 70 consecutive cases of transcervical hemostatic
      adenomectomy with the variation of capsule plasty, recently developed, after a
      previous experience of 1033 retropubic surgeries. We analyze the histologic
      findings in surgical specimens, biopsies of residual gland and prostate capsule,
      and confirmed the immediate changes surgery causes, measuring the volumes of
      residual prostate by ultrasound. As the base for comparisons we analyzed residual
      prostates from prostatectomies or radical cystoprostatectomy specimens in "young"
      patients. RESULTS/CONCLUSIONS: We obtained objective data about predominant and
      associated histological lesions found in adenomectomy specimens. In the same way,
      the same data were obtained from biopsies of peripheral residual prostate
      together with the volume of such zone, which should establish, if our hypothesis
      is right, the mid-long-term prognostic criteria for the approach to the so-called
      post operative reexpansion of the prostatic hollow and the possible establishment
      of new obstructive pathology.

PMID- 18077861
TI  - [Early ultrasound detection of renal tumors in patients with end stage renal
      disease in dialysis].
AB  - OBJECTIVES: Patients with end stage renal disease in dialysis are a population
      susceptible to suffer various types of cancers, mainly in the kidney and urinary
      tract. These tissues suffer systemic carcinogenic effects, including all that
      result from chemical and immunological changes secondary to renal failure, from
      the treatment they receive and dialysis itself. In the present article we
      determine the clinical, epidemiological, and pathological characteristics of
      patients with chronic renal failure in dialysis who presented renal tumors during
      the evolution of their disease over the last ten years. METHODS: We reviewed the
      medical charts of patients with chronic renal failure receiving dialysis in our
      institution who were diagnosed of renal tumors and received surgical treatment
      over the last 10 years. Patients with incomplete medical charts, HIV infection,
      and renal adult policystic disease were excluded from the study. RESULTS: 10
      tumors were detected in a total of nine patients with a mean age of 45.22 years
      (range 41-65 years), six males and three females; regarding the mean time from
      the start of dialysis to de diagnosis of the tumor: 5 appeared the first year, 2
      between 2 and 5 years, and 2 more than five years from the start of dialysis. The
      most frequent cause of chronic renal failure was high blood pressure, in 55.5% of
      the patients. 90% of the tumors were diagnosed incidentally during a control
      study, with ultrasound being the main diagnostic test (100%), a finding that was
      confirmed with MRI and CT scan in 60% and 30% of the patients respectively. The
      operative findings were: 8 solid masses, 1 mixed mass, and 1 cystic mass. Six
      patients underwent open surgery and 4 laparoscopic surgery. The most frequent
      pathologic diagnosis was clear cell carcinoma in 60% of the tumors. CONCLUSIONS:
      In our study population, we found that performance of periodic ultrasound
      controls enabled us to achieve early diagnosis and treatment of tumors of the
      kidney in patients in dialysis. Over the last years laparoscopy has become the
      treatment of choice for renal tumors, even in patients with chronic renal failure
      in dialysis.

PMID- 18077862
TI  - [Urodynamic test with self reduction of the cystocele in the diagnosis of lower
      urinary tract obstruction].
AB  - OBJECTIVES: The association of cystocele and urodynamic lower urinary tract
      obstruction is frequent, occasionally not being possible to rule out intrinsic
      obstruction of bladder neck and urethra. With the aim to confirm the obstructive
      character of the cystocele we performed at test consisting in manual reduction of
      the cystocele by the patient herself, to check if by this simple manoeuvre the
      urodynamic parameters of obstruction disappear or diminish. METHODS: 24 patients
      consulting for sensation of vaginal bulge, with a mean age of 66 years,
      participated in the study. The initial diagnosis of lower urinary tract
      obstruction and cystocele was obtained after video-urodynamic tests. The
      urodynamic test with self reduction of the cystocele was based on cystomanometry
      and voiding pressure-flow tests. The parameters of the study included presence,
      amplitude and bladder capacity during detrusor involuntary contractions in the
      cystomanometry; in the voiding pressure/flow test the parameters of the study
      were the URA as a urethra resistance parameter, the type of obstruction with the
      Chess classification, and Wmax and W80-W20 as parameters of detrusor
      contractility. RESULTS: A higher frequency of severe (58.3%) than moderate
      (41.6%) cystocele was demonstrated. No significant relation with age was
      demonstrated. The URA significantly diminished (p<0.01) with self reduction: from
      a median value of 30.5 before to 15.5 H2O cm after reduction. Although it was
      observed in all grades of cystocele, this reduction was greater in the severe
      ones. The most frequent type of obstruction was the constrictive (62.5%), over
      compressive (4.2%), mixed (12.5%) and unobstructed (4.2%). The constrictive
      obstruction significantly disappeared or diminished after reduction (p < 0.05) to
      a 45.8% of the cases, the compressive to 0%, the mixed to 4.2% and the
      nonobstructive to 50%. No significant relationship between these data and grade
      of cystocele was demonstrated. On the other hand, no significant differences were
      demonstrated with cystocele self reduction in the other urodynamic parameters
      (detrusor hyperactivity and contractility, Wmax and W80-W20), neither in their
      relationship with the grade of cystocele. CONCLUSIONS: This test could be very
      useful in the diagnosis of lower urinary tract obstruction for its validity and
      significance, apart from being an easy to perform and reproducible test.

PMID- 18077863
TI  - [Analysis of the efficacy and complications of the surgical treatment of stress
      urinary incontinence: retropubic and transobturator TVT. Our experience].
AB  - OBJECTIVES: To evaluate the differences in results and complications between
      retropubic and obturator TVT. METHODS: Descriptive prospective study including
      245 patients who underwent retropubic TVT and 90 obturator TVT after the
      diagnosis of stress urinary incontinence by means of clinical history, physical
      examination and urodynamic tests. Continence outcomes and Intraoperative/post
      operative complications were recorded. RESULTS: There were intraoperative
      complications in 12.65% of the retropubic TVT and 1.11% of the obturator TVT (p =
      0.002). Immediate post operative complications appeared in 24.5% of the
      retropubic TVTs and 12.2% of the obturator TVTs: severe anemia (0.4 vs. 1.1%),
      inguinal pain (1.2 vs. 4.4%), hematoma (1.6 vs. 0%), urinary tract infection
      (12.2 vs. 4.4%), and acute urinary retention (8.9 vs. 2.2%) (p = 0.018).
      Complications during follow-up: partial exteriorization of the mesh (0.81 vs.
      1.11%) and de novo urgency incontinence (9.38 vs. 4.44%) (p = 0.031). Post
      operative results were similar for both groups: 90.2% vs. 91.1% cured (p =
      0.046), improvement in 8.2% vs. 6.7% (p = 0.18) and failure in 1.6% vs. 2.2% (p =
      0.57). CONCLUSIONS: The obturator TVT seems to be preferable to retropubic TVT
      because it offers a lower complications rate without differences in post
      operative results in the short-term.

PMID- 18077864
TI  - [Multifilament polypropylene mesh with exteriozation of the silicone anchorage to
      the vagina].
AB  - OBJECTIVES: To describe the failure of one case of suburethral tape for the
      correction of the stress urinary incontinence with the multifilament Sapphire VS
      (vaginal-suprapubic approach) system after 34 months of good outcome. METHODS:
      Description of the case and its resolution. RESULTS: The patient presented with a
      descent of the lateral fixation and erosion of the vaginal mucosa with exposure
      of the mesh and infection. The silicone fixation system, which was loose, was
      retrieved very easily and a new suburethral mesh with the system TVT-O was
      inserted; the patient recovered continence as before. CONCLUSIONS: Synthetic mesh
      in the suburethral tape systems for stress urinary incontinence correction should
      be polypropylene, macropore and monofilament. These characteristics enable better
      bio integration, theoretically reducing the number of complications (vaginal wall
      erosion, exposition and over infection). In relation with the failure of the
      silicone fixation system, no other casers have been reported in follow-up studies
      between 12 and 36 months (mean follow-up 14 and 18 months), so hat studies with
      long-term follow-up will be able to determine if this is an isolated case or
      there will be others.

PMID- 18077865
TI  - [Greenlight KTP-laser photovaporization. Initial experience in a public
      hospital].
AB  - OBJECTIVES: Despite the fact that transurethral resection of the prostate (TURP)
      continues being the gold standard for the surgical treatment of benign prostatic
      hyperplasia (BPH), the good results obtained with the use of new energy sources
      have led to their use in daily practice. METHODS: Between September 2005 and
      January 2007, we have treated 63 patients with KTP laser photoselective
      vaporization of the prostate (PVP) in our service. Preoperatively we asked for
      IPSS, performed physical exam, digital rectal exam, abdominal , renal, bladder
      and prostatic ultrasound measuring postvoid residual volume, as well as flowmetry
      and PSA determination. Patients were revised after 1, 3, 6 and 12 months,
      undergoing uroflowmetry, IPSS, ultrasound and PSA; a satisfaction survey was also
      fulfilled at this interviews. RESULTS: Mean age was 67 years (range 58-85) and
      mean preoperative prostatic volume was 48cc (range 34-67), mean preoperative IPSS
      was 17.7 and mean maximum flow 8.1 mL/s. 12 patients presented post void residual
      volume larger than 100 mL. Most patients presented medium or high anaesthetic
      risk. Mean operative time was 64 minutes (range 45-95). In most cases we used
      just one fibre, and mean energy released was 175,000 Joules (range 85,000
      24,000). Mean hospital stay was 32.2 hours (range 19-55). In postoperative
      revisions we could state a significant decrease of IPSS, improvement in maximum
      flow, and also good or very good satisfaction degree in about 80% of the
      patients. Only 3 of them presented hematuria that needed to be attended by the
      urologist, none of them needed transfusion. One patient was admitted for severe
      urinary infection and eight patients referred irritative low urinary tract
      symptoms in their first postoperative checkup. CONCLUSIONS: KTP laser PVP is a
      safe, reproducible technique with optimal short and middle term outcomes, which
      should be considered as the first choice surgical treatment in elderly patients,
      patients with chronic anaemic diseases or anticoagulated, and patients with high
      anaesthesic or surgical risk.

PMID- 18077866
TI  - [Partial cystectomy. Our series].
AB  - OBJECTIVES: Partial cystectomy is a recognized bladder sparing surgical
      technique. Patient selection is essential in order to optimize long term results.
      We present our initial experience with laparoscopic partial cystectomy performed
      in a selected group of patients that includes both benign and malignant lesions.
      METHODS: Nine patients were surgically treated with laparoscopic partial
      cystectomy between July 2002 and September 2006 in our institution. Partial
      cystectomy was indicated for the treatment of a foreign body, endometriosis,
      urachal adenocarcinoma, trancisional cell carcinoma, acquired lesions of urachus
      and extravesical tumor. Analyzed surgical variables were operative time,
      conversion rate, blood loss, hospital stay and catheterization period. RESULTS:
      Nine patients with bladder lesions were laparoscopically operated for partial
      cystectomy. Transperitoneal technique was employed and no conversion to open
      surgery was performed. Median operative time was 77.77 min (range 30-120 min.).
      No patient received any transfusion. No intraoperative lesions were verified.
      Median hospital stay was 4.22 days (range 3-5 d.), median catheterization period
      was 7 days (range 5-10 d.). CONCLUSIONS: Laparoscopic partial cystectomy is a
      doable surgical procedure. It is a useful technique for both benign and malignant
      bladder disease. In TCC and urachal carcinoma oncological safety prevails.
      Patient selection is essential for this procedure.

PMID- 18077867
TI  - [Gunshot wound with a bullet lodged in the prostate].
AB  - OBJECTIVE: We describe a most unusual urological emergency: a firearm wound in
      which the blunt-nosed hand-gun bullet was lodged in the prostate. A bibliographic
      search of the literature revealed no similar case. METHODS: The patient was
      admitted presenting a gunshot wound with the entrance hole on the right buttock.
      There was no exit wound. An X-ray revealed the bullet behind the pubic symphysis.
      We introduced a suprapubic catheter and then carried out a laparotomy making a
      discharge colostomy Urethrogram revealed a pathway of contrast to the rectum.
      Several days later, we reached the bladder with an urethrotome and introduced an
      18 Fr catheter. Under radiological control we made an open approach to the
      retropubic space, palpated the bullet within the prostate and then removed it.
      DISCUSSION/CONCLUSIONS: The velocity of a rifle or hand-gun bullet is the main
      determinant of the severity of this type of injury. As there was no exit wound,
      we knew that the entrance velocity was low, therefore tissue damage would
      probably be small. In these cases, a preparatory suprapubic cystostomy is
      essential to be able to carry out a urethral reconstruction later. Radiological
      control during the procedure proved extremely useful to precisely locate the
      bullet. Our conservative approach of simply leaving in place the catheter helped
      us later to avoid a difficult repair of a recto-urethral fistula.

PMID- 18077868
TI  - [Unilateral adrenal hemorrhage and hypertensive crisis in a patient with
      antiplatelet treatment].
AB  - OBJECTIVE: We report a case of non-traumatic adrenal hemorrhage in a man with
      antiplatelet treatment. METHODS: The patient was admitted to the Critical Care
      Unit because of a non-controlled hypertensive crisis. Pheochromocytoma was
      analytically excluded. The patient underwent a delayed adrenalectomy. RESULTS:
      Pathologic study of the specimen showed a wide hemorrhagic necrosis. CONCLUSIONS:
      Association of high blood pressure and adrenal hemorrhage is not pathognomonic of
      pheochromocytoma.

PMID- 18077869
TI  - [Metanephric adenoma. Case report].
AB  - OBJECTIVE: Metanephric adenoma is an unfrequent renal neoplasm, usually
      asymptomatic. Differential diagnosis with other renal tumors has to be performed.
      METHODS/RESULTS: We report the case of a 67 years old woman with a metanephric
      adenoma. CONCLUSIONS: Metanephric tumors comprise a pathologic spectrum of
      lesions. At one end of the pathologic spectrum are the metanephric adenomas.
      These tumors usually behave in a benign fashion. It is important to differentiate
      metanephric adenoma from clinically aggressive renal tumors.

PMID- 18077870
TI  - [Intrauterine testicular torsion].
AB  - OBJECTIVE: We present the clinical case of an intrauterine testicular torsion.
      METHODS/RESULTS: Three days old boy complaining of testicular pain and scrotum
      enlargement with the diagnosis of intrauterine testicular torsion. Left
      testicular extirpation and right fixation were performed. CONCLUSIONS: We analyze
      cases reported, clinical diagnosis and therapeutic options. Testicular torsion
      can be misdiagnosed with other pathologies like tumors, testicular infarctions,
      hydrocele, etc. We should always consider it a surgical emergency. The future
      fertility of the patient can be compromised.

PMID- 18077871
TI  - [Leiomyosarcoma of the inferior vena cava. Incidental finding].
AB  - OBJECTIVE: Leiomyosarcoma of the inferior vena cava is a rare tumor, clinically
      silent which often remains undiagnosed for much longer. Imaging methods allow us
      to detect these entities. We report a single case and perform a bibliographic
      review. METHODS: 58-year-old woman with a 6 cm adrenal mass, which during surgery
      was found to be a tumor from the wall of the vena cava. We performed complete
      removal of the mass. Radiotherapy of the surgical area was applied within three
      months following surgery. RESULTS: Two years later, there is no evidence of
      disease recurrence. CONCLUSION: This is a rare entity, with low prevalence.
      Complete surgical excision is the gold standard for treatment. Local recurrence
      is a common finding during follow up.

PMID- 18077872
TI  - [Pheochromocytoma: laparoscopic treatment].
AB  - OBJECTIVE: We report this clinical case not only for the laparoscopic approach of
      a pheochromocytoma but also because of its particular aggressiveness and oddity
      of its clinical presentation. METHODS: 44 years old male presenting with
      oppressive chest pain with accompanying vegetative symptoms, who was diagnosed of
      right adrenal pheochromocytoma. RESULTS: After the diagnosis of pheochromocytoma
      was established and double adrenergic blockage implemented, transperitoneal
      laparoscopic surgery was performed. Pathological analysis of the surgical
      specimen confirmed the clinical diagnosis of pheochromocytoma. Patient was
      discharged home two days after surgery without any complication. CONCLUSIONS: The
      laparoscopic approach of adrenal pheochromocytoma is possible and safe in centres
      with laparoscopic experience, obtaining the same results than open surgery,
      offering advantages for the patient such as less pain, smaller incisions, and
      early ambulation, which results in a shorter hospital stay.

PMID- 18077873
TI  - [Seminal vesicle cyst with renal agenesis associated with vascular anomalies.
      Case report].
AB  - OBJECTIVE: We report a case of seminal vesicle cyst with ipsilateral renal
      agenesis associated wit abnormalities of the abdominal great vessels, not
      described previously in the bibliography. METHODS: 33 year-old-male with history
      of abdominal pain and fever. This case was evaluated by ultrasound, IV urography,
      CT scan and MRI. RESULTS/CONCLUSIONS. Congenital cystic disease of the seminal
      vesicle is an uncommon disorder. It is associated with genitourinary anomalies,
      often renal agenesis, and even anomalies of the lower spine. However, anomalies
      of the abdominal great vessels have not been described previously. CT scan
      provided excellent demonstration of associated anomalies.

PMID- 18077874
TI  - [Metastases in the paranasal sinuses secondary to prostatic adenocarcinoma].
AB  - OBJECTIVE: To report a new case of exceptional metastases from a prostatic
      carcinoma. METHODS: 64-year-old male with nine months history of disseminated
      prostate cancer, taking hormonal treatment and biphosphonates, who presents with
      rising PSA, facial dysesthesia and left exophtalmos. MRI recognizes the existence
      of a solid mass in the right maxillary sinus with involvement of the ipsilateral
      orbital floor, and another one in the left frontal sinus invading the roof of the
      ipsilateral orbit and also with orbital extraconal involvement. RESULTS: Once the
      diagnosis was established hormonal maneuvers were performed and chemotherapy with
      docetaxel was administered achieving at the start of treatment measurable disease
      stabilization with biochemical remission of PSA levels, followed posteriorly by
      progression without changes in the metastatic images. Currently new cytoreductive
      therapy with docetaxel has been initiated. CONCLUSIONS: 1% of the prostatic
      tumors involve the head in their evolution. Most frequent metastases are
      localized in the brain and meninges, being the involvement of paranasal sinuses
      and ocular orbit extraordinary. The importance of these comes from the extension
      to the orbit and the eye in vicinity. Second line hormonal maneuvers, local
      radiotherapy and systemic chemotherapy will be necessary for control, although
      results are discouraging. In general, prognosis is poor, with short survival.

PMID- 18077875
TI  - [Primary megaureter and obstruction].

PMID- 18077876
TI  - [Pressure ulcer secondary to penile prostheses].

PMID- 18077877
TI  - [Penile entrapment by metallic rings].

PMID- 18077878
TI  - Prof. Dr. Ramon Abascal Garcia's clear statement to fluorescence diagnosis of
      bladder cancer by 5- amino-levolinic acid.

PMID- 18077879
TI  - Muscle invasive bladder tumor 18 months after laparoscopic radical
      nephroureterectomy.
AB  - OBJECTIVE: The management of the distal ureter and bladder cuff is an important
      issue related to laparoscopic nephroureterectomy, because of the fear that local
      and bladder recurrences could be induced by an inadequate manipulation of the
      specimen. We present a case of muscle invasive bladder tumor that appeared 18
      months after laparoscopic radical nephroureterectomy. METHODS/RESULTS: A 42 year
      old woman with multifocal grade 3 pT3, right kidney urothelial carcinoma, treated
      by laparoscopic radical nephroureterectomy with early clipping of the distal
      ureter, transurethral detachment of the intramural ureter, and no bladder
      closure, presented with an invasive bladder recurrence after 18 months of follow
      up. CONCLUSIONS: There is no a definitive answer to the question of what is the
      best and safest way of treating the intramural ureter to prevent local and
      bladder recurrences. However, early clip occlusion of the ureter to avoid
      downstream cell seeding during kidney manipulation, and an open approach to the
      distal ureter in case of concomitant distal ureter or bladder tumor is
      recommended.

PMID- 18077880
TI  - IEEE transactions on visualization and computer graphics. Proceedings of the IEEE
      Visualization Conference and IEEE Information Visualization Conference. October
      28-November 1, 2007. Sacramento, California, USA.

PMID- 18077881
TI  - Proceedings of the CSB2007 Conference. August 13-17, 2007. San Diego, California,
      USA.

PMID- 18077882
TI  - [Newsreels as sources of cultural and social history: the category of gender in
      the West German newsreels of the 1950's].

PMID- 18077884
TI  - ACMT Position Statement: Dietary supplements.

PMID- 18077885
TI  - ACMT Position Statement: Institutions housing venomous animals.

PMID- 18077886
TI  - Questions about pesticides on foods.

PMID- 18077887
TI  - [The controversy about the relocation of the pharmacy faculty in Moravia in the
      1950's].

PMID- 18077889
TI  - The female dragons awake: women, sport and society in the early years of the new
      China.
AB  - This article, based on archival records, published documents, interviews with
      elite sportswomen and three regional case studies, deals with the radical social,
      economic, cultural and political changes in the early years of the Communist
      China, the consequent changes in women's lives and the eventual extraordinary
      impact on elite women's sport. It analyses the complicated relations between the
      communist system, gender ideology, sports policy, international politics and
      elite women's sport. With the establishment of a variety of sports institutions,
      systems and structures women in increasing numbers took part in competitive sport
      and produced even increasingly remarkable achievements.

PMID- 18077888
TI  - Phthalates in food and medical devices.

PMID- 18077890
TI  - Regarding the case report "Cerebral accident following MDMA ingestion".

PMID- 18077891
TI  - "A prey on normal people": C. Killick Millard and the euthanasia movement in
      Great Britain, 1930-55.

PMID- 18077892
TI  - National cancer control programs in Korea.

PMID- 18077893
TI  - A.N.Bach--a revolutionary in politics and science. Commemorating 150th
      anniversary of academician A.N. Bach.

PMID- 18077894
TI  - Festschrift in honor of Jordan Matthew Phillips, MD.

PMID- 18077895
TI  - Neuropsychoimmunology of psychoses. Immune and inflammatory aspects of psychoses.
      Abstracts of the 9th Psychoimmunology Expert Meeting. March 8-11, 2007.
      Reisensburg, Germany.

PMID- 18077896
TI  - [The 3rd Romanian National Conference of Pediatric Pneumology, June 14-16, 2007,
      Cluj-Napoca].

PMID- 18077897
TI  - Neuro-psychiatric disorders induced by Amiodarone high levels(Cordarone).

PMID- 18077899
TI  - Basic and clinical aspects of endothelial dysfunction. Proceedings of the 14th
      Jagiellonian Medical Research Centre Symposium. May 18-20, 2006. Krakow, Poland.

PMID- 18077898
TI  - [Accidental intrathecal vindesine administration: a report of two cases].

PMID- 18077900
TI  - Cosmonauts and lead: resorption and increased blood lead levels during long term
      space flight.

PMID- 18077901
TI  - Education or 'edutainment'?

PMID- 18077902
TI  - Comparative in vitro activity of tigecycline against aerobic and facultative
      isolates recovered from hospitalized patients: an Argentinean multicenter study.
AB  - Tigecycline, the 9-t-butylglycylamino derivative of minocycline is the first
      commercially available glycylcycline exhibiting an extended spectrum of
      antibacterial activity due to its capacity to evade the tetracycline ribosomal
      and efflux resistance mechanisms. We conducted a collaborative in vitro study
      determining the activity of tigecycline compared to 14 antimicrobials against
      clinically relevant isolates obtained from adult patients hospitalized in 9
      Argentinean institutions. Minimum inhibitory concentrations (MICs) were
      determined by the reference broth microdilution method. The number of isolates
      and MICs 50/90 (mg/L) for tigecycline were the following: Acinetobacter spp. 132
      (0.5/1); Escherichia coli 220 (0.12/0.25); Klebsiella spp. 220 (0.5/1),
      Enterobacter spp. 205 (0.5/1); Serratia spp. 84 (0.5/2); Haemophilus influenzae
      96 (0.25/0.5); Staphylococcus aureus 223 (0.12/0.25); Streptococcus pneumoniae 98
      (<or= 0.25/1); S. agalactiae 51 (0.5/0.5); Enterococcus spp. 104 (0.06/0.12);
      Pseudomonas aeruginosa 169 (8/16). We conclude that tigecycline is a promising
      drug for the treatment of infections in hospitalized patients in Argentina.

PMID- 18077903
TI  - Bullying: emotional and physical terrorism.

PMID- 18077904
TI  - [Advances in standardization and quality control for the analysis of sperm
      quality parameters].
AB  - Semen analysis is a basic test to evaluate male reproductive function. In recent
      years, urgent needs for the standardization of semen analysis have been
      emphasized among andrologists worldwide. This review discusses the
      standardization and quality control (QC) for the analysis of sperm quality
      parameters, including sperm concentration, motility and morphology. The key to
      sperm concentration analysis is the standardization of sperm-counting chamber,
      thus Cell-VU chamber may be the first choice. The analysis of sperm motility and
      morphology is too subjective to be reliable. Therefore, the computer-aided semen
      analysis (CASA) system may be the final selection. QC of semen analysis mainly
      lies in the selection of QC materials and the administration of external QC and
      internal QC. Meanwhile, the charts and arithmetic methods should be established
      to monitor QC of semen analysis.

PMID- 18077905
TI  - [Optimization of real time RT-PCR system for the quantitative estimation of
      CatSper1 mRNA levels in human and mouse mature spermatozoa].
AB  - OBJECTIVE: To establish and optimize a real time RT-PCR system for determining
      the transcript levels of CatSper1 in human and mouse mature spermatozoa
      containing microamount of RNA. METHODS: Total RNA of human and mouse mature
      spermatozoa was isolated by using TRIzol reagent and reversely transcribed to
      complementary DNA respectively. Primers for real time RT-PCR were designed in the
      homologous area of the human and mouse CatSper1 mRNAs. Human sperm complementary
      DNA was used as the template to the optimize the conditions for SYBR Green I real
      time RT-PCR, including annealing temperature, Mg2+ concentration, fluorescence
      measurement temperature and the ratio between forward and reverse primers. The
      standard curve was constructed with serial dilutions of complementary DNA from
      human sperm to ascertain the amplification efficiency of SYBR Green I real time
      PCR and to quantitate the CatSper1 mRNA levels in the human and mouse mature
      spermatozoa. RESULTS: The optimal conditions for real time RT-PCR, that is,
      annealing temperature, Mg2+ concentration and the ratio between forward and
      reverse primers were 63 degrees C, 3.0 mmol/L and 1:1 respectively. The
      fluorescence measurement temperature was 88 degrees C. The standard curves were Y
      = -3.402 log (X) + 25.99 and Y = -3.409 log(X) + 24.09 in the human sperm cDNA
      and mouse sperm cDNA as the template, with amplification efficiency of 96.8% and
      96.5% respectively. The R2 value (an indicator of the quality of the fit of the
      standard curve to the standard data points plotted) of both standard curves was
      0.998. The CatSper1 mRNA levels in the human and mouse mature spermatozoa could
      be determined according to the standard curve. CONCLUSION: The general RT-PCR
      system, by adding SYBR Green I and optimizing its conditions, could be used to
      quantitate the mRNA levels in both human and mouse mature spermatozoa.

PMID- 18077906
TI  - [Cloning of gdnf in the mouse testis and its expression in sertoli cells].
AB  - OBJECTIVE: To clone the glial cell line-derived neurotrophic factor (GDNF) from
      the mouse testis, construct the eukaryotic expression vector and transfect this
      vector into Sertoli cells in order to use the gdnf-transfected Sertoli cells as
      the feeder layer to cultivate spermatogonial stem cells (SSCs). METHODS: Total
      RNA was extracted from the testes of normal mature mice and gdnf was cloned and
      amplified using RT-PCR, inserted into the eukaryotic expression vector and
      transfected into sertoli cells (TM4 cell line). Immunofluorescence with anti-GDNF
      antibodies was performed at 40 h following the transfection. RESULTS: gdnf cDNA
      was cloned successfully, and GDNF expressed after transfected into Sertoli cells.
      CONCLUSION: This study provides a basis for culturing SSCs with gdnf-transfected
      Sertoli cells as the feeder layer.

PMID- 18077907
TI  - [PDCD5 induces the apoptosis of human prostate cancer cells PC-3M-1E8].
AB  - OBJECTIVE: To investigate the apoptosis-promoting effect of PDCD5 on human
      prostate cancer cells PC-3M-1E8. METHODS: PCI-neo and PCI-neo-PDCD5 were
      transfected into PC-3M-1E8 cells by Lipofectamine 2000, the viability of the
      cells was analyzed by MTT assay 16 hours after removal of the serum, and the
      apoptosis was determined by in situ end-labeling and electron microscopy.
      RESULTS: The viability and growing speed of the transfected cells were
      significantly decreased and their apoptotic indexes significantly increased as
      compared with the control group (P < 0.001). CONCLUSION: PDCD5 may significantly
      inhibit the in vitro growth and promote the apoptosis of human prostate cancer
      cells PC-3M-1E8.

PMID- 18077908
TI  - [RNA interference inhibits the expression of survivin and induces the apoptosis
      of PC-3 cells].
AB  - OBJECTIVE: To investigate the inhibitory effect of RNA interference (RNAi) on the
      expression of survivin mRNA and its inducibility of the apoptosis of PC-3 cells.
      METHODS: siRNA expression vectors were designed and constructed to be directed at
      survivin and transfected into PC-3 cells by Lipofectamine in 4 groups: plasmid A,
      plasmid B, negative sequence and control E. RT-PCR, Western blot and flow
      cytometry were used to detect the expression of survivin mRNA and the apoptosis
      of PC-3 cells. RESULTS: The expression rates of survivin protein were 18.94% +/-
      0.63%, 16.35 +/- 0.23%, 46.41% +/- 0.76% and 46.20 +/- 1.47%, those of survivin
      mRNA were 27.94% +/- 1.43%, 24.51% +/- 1.37%, 49.46% +/- 0.71% and 48.49% +/-
      1.32%, and the apoptosis rates of PC-3 cells were 12.80% +/- 1.33%, 16.48% +/-
      1.00%, 3.03% +/- 0.62% and 2.96% +/- 0.41% respectively in different groups.
      CONCLUSION: RNAi can effectively inhibit the expression of survivin mRNA and
      induce the apoptosis of PC-3 cells.

PMID- 18077909
TI  - [Over-expression of hypoxia-inducible factor-1 alpha increases angiogenesis of
      LNCaP cells].
AB  - OBJECTIVE: To evaluate the effect of hypoxia-inducible factor-1 alpha (HIF-la) on
      angiogenesis in human prostate cancer cells. METHODS: Human prostate cancer cells
      of the line LNCaP were cultured and transfected by the recombinant plasmid
      pcDNA3. 1(-)/HIF-1alpha containing the gene HIF-1alpha with the Lipofectamine
      2000 system. The positive clone cells were selected by G418 and confirmed by
      Western blotting and immunofluorescence (LNCaP/HIF-1alpha cells). The expressions
      of VEGF, iNOS and Ang-2 were detected by Western blotting. RESULTS: The
      expression of HIF-1alpha in the LNCaP/HIF-1alpha cells was distinctly higher than
      that in the LN-CaP cells. Compared with the LNCaP cells, the expressions of VEGF
      and iNOS were up-regulated, whereas Ang-2 remained unchanged in the LNCaP/HIF
      1alpha cells. CONCLUSION: The over-expression of HIF-1alpha can induce an
      increase in angiogenesis proteins and improve the angiogenesis potency of
      prostate cancer.

PMID- 18077910
TI  - [Expression patterns of age-related molecule c-kit, HIWI and vimentin in the rat
      testis and epididymis].
AB  - OBJECTIVE: To examine the differences in the expressions of c-kit, HIWI and
      vimentin in the testis and epididymis of rats aged different months, investigate
      the regular changes in the expression of characteristic molecules in the ripening
      and senescent process of the testis and epididymis, and provide experimental
      evidence for studies on the aging of the male reproductive system. METHODS:
      Sprague-Dawley male rats were divided into a young group (6-month-old, n=10), an
      adult group (12-month-old, n=10) and an aged group (24-month-old, n=10). The
      immunohistochemical SP method was used to examine c-kit, HIWI and vimentin in the
      testis and epididymis of the rats. RESULTS: The positive immunohistochemical
      reaction to c-kit was observed mainly in spermatogonia, weakly in other cells and
      also in the epithelia and lumens of the epididymis. The abundant expression of
      HIWI was detected in all stages of spermatogenic cells in the testis and
      epididymis of the 6-month-old and 12-month-old rats. Moreover, spermatogonias and
      primary spermatocytes displayed intense expression. Sertoli cells, Leydig cells,
      myoid cells and vascular endothelial cells (VEC) were also HIWI-positive cells.
      But the positive expression decreased with age in the testis and epididymis of
      the 24-month-old rats (P > 0.05). vimentin expression was weak in the testis and
      epididymis of the 6-month-olds but increased significantly in the 24-month-olds
      (P > 0.01). CONCLUSION: The expressions of c-kit and HIWI decreased in the testis
      and epididymis of the 24-month-old rats, while vimentin expression increased
      markedly with age. The results suggest that the aging of the testis and
      epididymis is closely related to the abnormal transduction of cell signals.

PMID- 18077911
TI  - [Expression of prostate cancer antigen-1 in prostate cancer and its clinical
      significance].
AB  - OBJECTIVE: To investigate the expression of prostate cancer antigen-1 (PCA-1) in
      different prostate tissues and analyze its correlation with the clinical
      parameters of prostate cancer (PCa). METHODS: The expression of PCA-1 mRNA was
      detected by RT-PCR in the samples from 45 cases of PCa with various clinico
      pathologic characteristics, 30 cases of high-grade prostatic intraepithelial
      neoplasia (HG-PIN), 43 cases of BPH and 39 cases of other carcinoma tissues. The
      correlation of PCA-1 mRNA expression with the clinical parameters of PCa was
      statistically analyzed and the PCA-1 expression was examined in different samples
      by immunohistochemistry. RESULTS: The positive expression rate of PCA-1 mRNA was
      88.9% and 60.0% and that of PCA-1 protein was 84.4% and 50.0% in the patients
      with PCa and HG-PIN, respectively. PCA-1 mRNA and PCA-1 proteins were not
      expressed in the BPH and other carcinoma tissues. The expression of PCA-1 mRNA
      was unrelated with the clinical parameters of PCa (P > 0.05). CONCLUSION: It is
      suggested that PCA-1 is a PCa-specific gene and its expression is unrelated to
      the clinical parameters of PCa. It might serve as a specific biomarker for the
      early diagnosis of PCa.

PMID- 18077912
TI  - [Genotype analysis of CYP1A2 IVS4 + 43A/G in patients with prostate cancer].
AB  - OBJECTIVE: To investigate the genotype of the single nucleotide
      polymorphisms(SNP) of CYP1A2 IVS4 + 43A/G in patients with prostate cancer by
      TaqMan allelic discrimination. METHODS: TaqMan SNP allelic discrimination was
      performed with the ABI 7300 system to detect the genotype of CYP1A2 IVS4 + 43A/G
      in 85 patients with prostate cancer. RESULTS: The genotypes of CYP1A2 IVS4 +
      43A/G in the patients were as follows: AA subtype in 5 cases (5.9%), AG in 33
      (38.8%), and GG in 47 (55.3%). Each subtype of CYP1A2 IVS4 + 43A/G was not
      correlated with the Gleason score of prostate cancer. CONCLUSION: There was no
      significant correlation between SNP of CYP1A2 and the differentiation of prostate
      cancer.

PMID- 18077913
TI  - [Transrectal high-intensity focused ultrasound with the Sonablate 500 for the
      treatment of prostate cancer].
AB  - OBJECTIVE: To evaluate the clinical effect of transrectal high-intensity focused
      ultrasound (HIFU) in the treatment of prostate cancer (PCa). METHODS: A total of
      57 PCa patients, 27 localized and 30 advanced, underwent transrectal HIFU with
      the Sonab- late 500, the localized group treated by transrectal HIFU only, while
      the advanced group by transrectal HIFU combined with androgen ablation. RESULTS:
      For the HIFU treatment, the mean operating time, hospital stay and follow-up were
      111 mm (ranging from 86 to 153 mm), 3.2 days (ranging from 2 to 18 days) and 18
      months (ranging from 6 to 30 months), respectively. The biochemical disease-free
      rates at 1, 2 and 3 years in the localized group were 86%, 81% and 79%,
      respectively. While in the advanced group, the serum prostate specific antigen
      (PSA) was < 4.0 microg/L in 26 cases ( < 0.51 microg/L in 20) and the prostate
      volume decreased more than 50% in 21 cases after treated for an average of 8
      months (ranging from 3 to 24 months). After transrectal HIFU prostate ablation,
      the prostate volume reduced, serum PSA lowered, Qmax raised and IPSS improved
      significantly (P < 0.05). No serious complications occurred including severe
      urethrorectal fistula and incontinence. CONCLUSION: Transrectal HIFU is a safe,
      effective and minimally invasive therapy for patients with prostate cancer.

PMID- 18077915
TI  - [Extraperitoneal laparoscopic radical prostatectomy for prostate cancer: a report
      of 65 cases].
AB  - OBJECTIVE: To report the experience with extraperitoneal laparoscopic radical
      prostatectomy (EP-LRP) in the treatment of prostate cancer. METHODS: Sixty-five
      patients with diagnosed localized prostate cancer underwent extraperitoneal
      laparoscopic radical prostatectomy. RESULTS: The procedures were successful in 64
      cases. Mean operating time was 172 min (range 100 to 440 min). Mean blood loss
      was 340 ml (range 150 to 800 ml). Seven (10.8%) of the 65 patients received
      transfusion with MAP of 24 units. Rectal injury occurred in 1 patient, 2
      developed urethrovesical anastomotic leakage, 6 (9.2%) had positive surgical
      margins, 58 (89.2%) were fully continent with urination 3 months after the
      operation. CONCLUSION: EP-LRP, as a safe and feasible procedure for prostate
      cancer, which avoides violation of the peritoneal cavity, potentially decreases
      the risk of intraoperative complications and further reduces postoperative
      morbidity, is well worth popularizing.

PMID- 18077916
TI  - [Determination of uric acid in seminal plasma and correlation between seminal
      uric acid and semen parameters].
AB  - OBJECTIVE: To establish the method of seminal uric acid (UA) determination and
      investigate the correlation between the seminal UA level and semen parameters.
      METHODS: The method of seminal UA determination was established by modifying the
      method of serum UA detection, and its intraassay coefficient of variation (CV)
      and the difference of the results between different technicians were also
      observed to evaluate the acceptability of the method. In the meanwhile, the
      correlations of the seminal UA level with the patients' age, abstinence time,
      semen volume, pH, sperm concentration, motility, the percentage of grade a and b
      sperm, and the percentage of morphologically normal sperm. RESULTS: The
      intraassay CV was 9. 16% for the method of seminal UA detection, and there was no
      significant difference in the UA level detected by 2 technicians (P = 0.541). The
      seminal UA level was positively correlated with the percentage of morphologically
      normal sperm (r = 0.350, P = 0.025) , with a tendency of positive correlation
      with sperm motility (r = 0.147, P = 0.085) and the percentage of grade a and b
      sperm (r = 0.156, P = 0.068), but not with other parameters such as semen volume,
      pH, sperm concentration, abstinence time and the patients' age. CONCLUSION: An
      acceptable method of seminal UA determination could be established by modifying
      the method of serum UA detection. Sperm morphology, motility and the percentage
      of grade a and b sperm might be related to the level of seminal UA.

PMID- 18077917
TI  - [Length and volume of intravesical prostatic protrusion closely correlated with
      bladder outflow obstruction in BPH patients].
AB  - OBJECTIVE: To analyze the correlation of the length and volume of intravesical
      prostatic protrusion (IPP) with bladder outflow obstruction (BOO) in patients
      with BPH and to find a simple method for the diagnosis of the disease. METHOD:
      The length and volume IPP were measured by transrectal ultrasound for 87 patients
      with BPH, the diagnosis of BOO was made by urodynamic tests and the correlation
      of the length and volume of IPP with BOO was analyzed, and reanalyzed 3 months
      after oral medication of a-blocker. The length and volume of IPP were measured
      again during the operation in 54 of the cases to confirm the ultrasound findings.
      RESULTS: BOO was diagnosed in 51 of the patients. The coefficient of correlation
      between the length of IPP and BOO and that between the volume of IPP and BOO were
      0.53 and 0.47 (P < 0.01). Not considering the dynamic factors, they were 0.69 and
      0.62 (P < 0.01), respectively. BOO was confirmed in patients with the length of
      IPP > 1.0 cm or the volume > 1.5 ml. There was no significant difference between
      the results of transrectal ultrasound and the findings during the operation
      concerning the length and volume of IPP (P > 0.05). CONCLUSION: There is a close
      correlation between the length and volume of IPP and BOO, which can be
      conveniently applied to the diagnosis of BOO in BPH patients.

PMID- 18077918
TI  - [Progress in pharmacotherapy of female sexual dysfunction].
AB  - Recent years have seen great progress in the researches on the pharmacotherapy of
      female sexual dysfunction( FSD). Estrogen replacement therapy is effective on
      female sexual pain and dyspareunia; androgen can improve female hyposexuality;
      and a variety of drugs and medication forms are being studied for their efficacy
      on FSD, including the 5-phosphodiesterase inhibitor, dopamine receptor stimulant,
      prostaglandin E1, adrenergic receptor blocker, some traditional Chinese medicine,
      and so on, which have yielded lots of inspiring findings.

PMID- 18077919
TI  - [Update of the researches on the niche for spermatogonial stem cells].
AB  - Spermatogonial stem cells are a population of immortal cells, capable of self
      renewal and multi-directional differentiation. The theory of the "stem cell
      niche" was originally proposed for the hematopoietic system, and niches also
      exist in testicular tissues. The niche for spermatogonial stem cells is a semi
      isolation system, characteristic of specific number regulation and changing with
      the age. The self-renewal of spermatogonial stem cells is regulated by two
      endogenous factors, nanos2 and Plzf, as well as by the niche cell-excreted
      factor, glial-derived neurotrophic factor (GDNF).

PMID- 18077920
TI  - [Clinical observation of Qanliexian decoction in the treatment of NIH III A
      prostatitis].
AB  - OBJECTIVE: To study the efficacy of Qianliexian Decoction in the treatment of
      National Institute of Health (NIH) III A prostatitis. METHODS: Forty-six patients
      with NIH III A prostatitis were treated by oral Qianliexian Decoction 1 dose and
      twice a day for 30 days. The results of the treatment were evaluated according to
      the NIH chronic prostatitis symptom index (NIH-CPSI) and leukocyte counts in the
      expressed prostatic secretions (EPS). RESULTS: The overall scores before and
      after the treatment were (32.3 +/- 7.4) and (17.8 +/- 4.2) on NIH-CPSI (P <
      0.01), (13.2 +/- 3.6) and (7.8 +/- 2.3) on pain or discomfort (P < 0.01), (4.5 +/
      1.2) and (1.4 +/- 0.8) on urinary symptoms (P < 0.01), (14.6 +/- 7.4) and (8.6
      +/- 3.5) on the quality of life (P < 0.01), and (20.6 +/- 2.4) /HP and (5.6 +/-
      3.2)/HP on leukocyte counts, respectively. The decoction cured 8 of the patients
      and was shown to be obviously effective in 11 cases, effective in 20 and
      ineffective in 7, with a total efficacy rate of 84.78%. CONCLUSION: Qianliexian
      Decoction is quite effective for the treatment of NIH III A prostatitis.

PMID- 18077921
TI  - Degradation of 24S-hydroxycholesterol in men is not regulated by CYP7A1.
AB  - OBJECTIVE: The conversion of cholesterol into bile acids occurs via a long
      cascade of enzymatically regulated oxidative processes. Our aim was to examine if
      an up-regulation of hepatic cholesterol 7alpha-hydroxylase (CYP7A1) in humans by
      cholestyramine, a bile acid-binding resin, has an effect on the degradation of
      brain-specific 24S-hydroxycholesterol. PATIENTS AND METHODS: Six
      normocholesterolemic male volunteers received 4 g cholestyramine b.i.d. for 2
      weeks in an open, prospective exploratory trial. Serum concentrations of
      lipoproteins and triglycerides were measured by routine enzymatic assays. Sterols
      and oxysterols were measured by gas chromatography/mass spectrometry. RESULTS:
      Total and LDL-cholesterol decreased on the average by 9.3% (p = 0.002) and 19.8%
      (p = 0.001) after 2 weeks of treatment, respectively. Absolute serum
      concentrations of 7alpha-hydroxycholesterol, a marker for bile acid production,
      increased 4-fold after 2 weeks, while 24S- and 27-hydroxycholesterol remained
      unchanged. Treatment with cholestyramine elevated serum levels of lathosterol, an
      indicator for the endogenous synthesis of cholesterol, by 146% (p = 0.009).
      CONCLUSION: In addition to lowering serum concentrations of total cholesterol and
      LDL-cholesterol, cholestyramine at a dose rate of 4 g b.i.d. causes a significant
      increase in the CYP7A1 catalyzed 7alpha-hydroxylation of cholesterol and an up
      regulation of endogenous cholesterol synthesis, as proven indirectly by an
      increase in serum lathosterol levels. Total serum levels of 24S- and 27
      hydroxycholesterol remained unchanged indicating that an up-regulation in CYP7A1
      activity is not responsible for the subsequent oxidative degradation of these
      hydroxylated sterols.

PMID- 18077922
TI  - A randomized, double-blind, vehicle-controlled, half-side comparison with a
      herbal ointment containing Mahonia aquifolium, Viola tricolor and Centella
      asiatica for the treatment of mild-to-moderate atopic dermatitis.
AB  - OBJECTIVE: Only a few clinical trials have been published on the topical
      treatment of atopic dermatitis with herbal ointments. An ointment containing
      extracts from Mahonia aquifolium, Viola tricolor and Centella asiatica has
      previously been studied in open uncontrolled trials with children. However, no
      data exist on adult patients in a randomized controlled trial. METHODS: A total
      of 88 patients with mild-to-moderate atopic dermatitis were enrolled in a double
      blind, vehicle-controlled, randomized, half-side comparison. Patients between 18
      and 65 years of age were treated for 4 weeks with an ointment containing Mahonia
      aquifolium, Viola tricolor and Centella asiatica. The primary endpoint was a
      summary score for erythema, edema/papulation, oozing/crust, excoriation and
      lichenification according to a 4-point scale. Secondary efficacy variables were
      assessment of pruritus severity (10 cm VAS) and a global assessment of
      effectiveness as well as tolerability. RESULTS: The study ointment reduced the
      primary and secondary endpoints slightly more than the base cream which was used
      as vehicle; the differences were not statistically significant. Since the
      climatic conditions during the study duration varied from very mild and sunny to
      very cold and dry, a post-hoc subanalysis was performed with a subset of 64
      patients whose treatment was at a mean outside temperature of 10 degrees C or
      less. Under these conditions the primary endpoint showed high statistical
      significance. CONCLUSION: In this trial, an ointment containing Mahonia
      aquifolium, Viola tricolor and Centella asiatica could not be proven to be
      superior to a base cream for patients with mild-to-moderate atopic dermatitis.
      However, a subanalysis indicated that the cream might be effective under
      conditions of cold and dry weather.

PMID- 18077923
TI  - Hoek's formula, a cystatin C-based prediction formula for determining the
      glomerular filtration rate, is the most effective method for original adjusting
      the dosage of vancomycin.
AB  - OBJECTIVE: Some formulas using the serum cystatin C level to estimate the GFR
      have recently been reported. However, there has been no report of a serum
      cystatin C-based formula for adjusting the dosage of the drugs cleared by the
      kidney. In this study, we compared the predictive performance of the serum
      vancomycin trough concentration predicted using serum cystatin C-based formulas.
      METHOD: The data were collected from 158 hospitalized patients. Five formulas
      have been published to predict the GFR using serum cystatin C. The cystatin C
      based formulas were divided into two groups, formulas with or without
      anthropometric data. We predicted the serum vancomycin trough concentrations
      using VCM-TDM S_edition ver. 1.00 software. RESULTS: In formulas with
      anthropometric data, the mean absolute error (MAE) using Hoek's formula was 2.38,
      the MAE using Grubb's 1 formula was 4.13, the MAE using Sjostrom's formula was
      2.90, and the MAE using Cockcroft and Gault formula based on creatinine was 4.42.
      On the other hand, in formulas without an anthropometric data group, the MAE
      using Larsson's formula was 3.07, and the MAE using Grubb's 2 formula was 3.63.
      CONCLUSION: These results suggested that Hoek's formula is the most useful
      formula for determining the initial dosage settings for vancomycin.

PMID- 18077924
TI  - The association of interferon with the development of pulmonary tuberculosis.
AB  - We report a new case of a patient suffering from chronic hepatitis C (CHC) and
      treated with interferon-alpha2a (IFN-alpha) who presented with the diagnosis of
      active pulmonary tuberculosis. Interferon was stopped and appropriate treatment
      with antituberculous drugs initiated. Several weeks later the patient was free of
      clinical symptoms. Our case demonstrates a rare association between interferon
      and tuberculosis since only one case in the literature has described a similar
      association.

PMID- 18077925
TI  - Potential adverse effects of a low-dose aspirin-diuretic combination on kidney
      function.
AB  - OBJECTIVE: Low-dose aspirin and diuretics are commonly co-utilized in patients
      with cardiovascular diseases. The objective of this study was to investigate the
      effects of a low-dose aspirin-diuretic drug combination on renal function.
      METHODS: In this cross-sectional retrospective study, all patients, excluding
      those on renal dialysis, admitted to the Internal Medicine Department of the Al
      Watani Hospital, Nablus, Palestine, were included in the study. Medical data were
      obtained from patients' medical files. Estimation of creatinine clearance was
      carried out using the Cockcroft-Gault equation. Patients on the target drug
      combination were compared with patients who were not receiving the target drug
      combination. An independent paired t-test and 1-way ANOVA were used to test for
      significance between groups. Statistics were carried out using the Statistical
      Package for Social Sciences (SPSS), version 13. RESULTS: A total of 340 subjects
      (54.4% men) were included in the study. There were 90 patients on the target drug
      combination and designated as the study group. Of the remaining 250 patients
      comprising the control group, 114 received none of the target drugs and 136
      received only one target medication. There was a significant (p < 0.001)
      difference in the levels of creatinine clearance between the two groups. Patients
      on the target drug combination had significantly lower creatinine clearance
      levels than those in the control group. Men in the study group had lower
      creatinine clearances than men in the control group and similar results were
      found for women. Patients in the study group with > or = 2 chronic diseases, had
      lower creatinine clearances than patients in the control group with > or = 2
      chronic diseases. Similar results were found in patients with < 2 chronic
      diseases. CONCLUSION: Administration of a low-dose aspirin-diuretic drug
      combination was associated with significantly lower creatinine clearance levels.
      This finding was independent of gender and the number of chronic diseases
      present. Monitoring kidney function in patients receiving this drug combination
      is recommended.

PMID- 18077926
TI  - Successful desensitization protocol for hypersensitivity reactions caused by
      oxaliplatin.
AB  - OBJECTIVE: To report the successful desensitization of a patient with a
      hypersensitivity reaction to oxaliplatin. CASE SUMMARY: A 57-year-old woman with
      metastatic colon cancer was receiving oxaliplatin, fluorouracil and leucovorin
      every 2 weeks and showed a partial response to therapy. During the fourth cycle,
      an anaphylactic reaction with palpitations and rash occurred. The patient was
      hypotensive with mild pulmonary wheezing. Since oxaliplatin was the probable
      cause of the hypersensitivity reaction, therapy with this drug was discontinued.
      Therapy in the patient was continued using cetuximab and irinotecan but this
      resulted in progression of the cancer. In view of the initial satisfactory
      response to the oxaliplatin-based regimen, it was decided to attempt
      desensitization to oxaliplatin using a protocol adapted from carboplatin
      regimens. The desensitization procedure was successful and the patient
      subsequently tolerated an additional three cycles using this regimen without
      further symptoms of hypersensitivity. DISCUSSION: In cases with moderate-to
      severe reactions to oxaliplatin, reexposure is not usually considered. However, a
      need to use first-line therapy when there is recurrence of the cancer has
      encouraged the development of rapid desensitization procedures which allow
      patients to be treated with medications to which they have previously shown
      hypersensitivity reactions. A combination of premedication using intravenous
      dexamethasone and a desensitization regimen was designed which was used
      successfully to increase concentrations and flow rates of oxaliplatin.
      CONCLUSIONS: Hypersensitivity reactions to oxaliplatin are not rare and
      physicians need to be aware of these. When substitution of another antineoplastic
      drug is not feasible, oxaliplatin desensitization should be considered even when
      hypersensitivity reactions to oxaliplatin are severe.

PMID- 18077927
TI  - Paroxetine oral solution is bioequivalent to paroxetine tablets--advantages of
      the solution.
AB  - OBJECTIVE: This study was undertaken to compare the pharmacokinetic profiles of
      paroxetine oral solution and paroxetine tablets in healthy volunteers under
      fasting conditions. METHODS: In this randomized, open-label, single-dose, 2-way
      cross over, laboratory-blind bioequivalence study healthy volunteers alternately
      received one 20 mg dose paroxetine as an oral solution (20 mg/20 drops) and one
      20 mg dose paroxetine as a tablet. Doses were separated by a 23-day interval.
      RESULTS: A total of 48 subjects enrolled in the study; there were 26 males and 22
      females with a median age of 25.5 years and a median weight of 73.6 kg. Both
      formulations were well tolerated, with no serious adverse events reported. Two
      subjects discontinued the study. Paroxetine was rapidly absorbed, the rate and
      extent of absorption of the two formulations were similar, and no statistically
      significant differences in half-life were observed between formulations.
      CONCLUSION: The oral solution and tablet formulations of paroxetine were
      bioequivalent and therefore may be safely interchanged. The oral solution may be
      a useful tool to ease administration and for tapering off paroxetine treatment.

PMID- 18077928
TI  - Bioequivalence evaluation of 320 mg gemifloxacin tablets in healthy volunteers.
AB  - This study was done to compare the bioavailability of a new tablet formulation of
      gemifloxacin (gemifloxacin 320 mg/tablet) with that of the reference product
      (factive 320 mg/tablet). The bioequivalence of a single dose (320 mg) was
      assessed for gemifloxacin included in the test and reference products by
      comparing the pharmacokinetic parameters derived from the plasma concentration
      time profiles following administration to 24 healthy male volunteers in a
      balanced, 2-period, 2-sequence, 2-way crossover design. Plasma concentrations of
      gemifloxacin were analyzed by a validated and sensitive HPLC assay developed in
      house. The mean plasma concentration-time profiles are almost superimposable. 18
      ANOVAs were performed to compare gemifloxacin plasma levels of the two
      formulations at each sampling time and there were no statistical differences
      between the two formulations. The parameters used to measure bioavailability were
      AUC0-t, AUC0-infinity and Cmax and they were calculated by a model-independent
      method. The parametric 90% confidence intervals of the mean values for the
      test/reference ratio were in each case well within the bioequivalence acceptable
      boundaries of 80-125% for AUCo-t, AUC0-infinity and Cmax. Data obtained in this
      study prove, by appropriate statistical methods, the essential similarity of
      plasma levels of gemifloxacin from the test product with those from the reference
      product suggesting equal clinical efficacy of these two products.

PMID- 18077929
TI  - [Obesity and overweight in dogs].

PMID- 18077930
TI  - Review of genetic aspects of radiological alterations in the navicular bone of
      the horse.
AB  - Navicular disease or podotrochlosis has long been known to cause forelimb
      lameness in horses. It had been proposed that the development of podotrochlosis
      has similarities to the human osteoarthritis (OA) complex. Alterations of the
      navicular bone can be made visible early in life only on the basis of
      radiographs. Reports on the prevalences of navicular disease indicate that
      radiological alterations in the navicular bone are present in different warmblood
      populations at frequencies of between 14.9% and 87.6%. Genetic factors play an
      important role in the development of the radiological signs. Estimates of
      heritability using animal threshold models range from h2 = 0.09 to h2 = 0.40.
      Estimated additive genetic correlations between radiological changes in the
      navicular bone and other orthopaedic health traits indicated that they mostly
      develop genetically independently of each other. There was a negative genetic
      correlation between radiological changes in the navicular bone and the number of
      tournament entries and placings. It has also been shown that reduction of
      radiological changes of navicular bones and improvement of breeding values for
      performance of riding horses can be achieved if selection is based on breeding
      values for these traits simultaneously. An optimised markerset was developed to
      detect quantitative trait loci (QTL) for pathologic changes in the navicular bone
      of Hanoverian warmblood horses. The horse genome was scanned using 214 highly
      polymorphic microsatellites chromosome-wide significant QTL were located on
      equine chromosomes (ECA) 2, 3, 4, 10, and 26. Genome-wide significant QTL were on
      ECA2 and on ECA10. Unravelling QTL associated with navicular disease will enhance
      selection progress for a healthy limb constitution in horses.

PMID- 18077931
TI  - Efficacy of lyophilised C-strain vaccine after oral immunisation of domestic pigs
      and wild boar against classical swine fever: first results.
AB  - The aim of this study was to evaluate the efficacy of lyophilised C-strain
      vaccine in domestic pigs and wild boar after oral application. A new spherical
      bait form (diameter 3 cm) containing lyophilised vaccine virus and the recent
      vaccine baits were used for animal experiments. Four vaccination groups were
      established in experiment 1 (group 1: recent liquid bait vaccine; group 2:
      spherical baits containing one dose of the lyophilised vaccine; groups 3
      (domestic pigs) and 4 (wild boar): spherical baits containing two doses of the
      lyophilised vaccine) and two groups in experiment 2 (group 1: recent liquid bait
      vaccine; group 2: spherical baits with two doses of the lyophilised vaccine).
      Challenge was carried out with the highly virulent virus strain "Alfort 187"
      (using 100 TCID50 in the first and 1.000 TCID50 in the second experiment). Our
      results showed that the animals vaccinated with lyophilised C-strain vaccine
      developed high neutralising antibody titres comparable to those obtained after
      vaccination with the recent bait vaccine. All pigs which picked up the baits
      remained healthy after challenge. Neither clinical symptoms nor viremia or virus
      shedding were observed after infection except in one pig (group 2, experiment 2)
      which had not consumed the vaccine bait. The surviving domestic pigs and wild
      boar were tested negative for CSFV and viral RNA at the end of the study. This
      result demonstrates that lyophilised vaccine may become an effective vaccine
      formulation for oral immunisation of wild boar against CSF in the near future.

PMID- 18077932
TI  - [The efficacy of local anaesthetics administered prior to castration of male
      suckling piglets].
AB  - Objective of this study was to examine the efficacy of various local anaesthetics
      (Procaine Hydrochloride, Procaine Hydrochloride + Epinephrin, Lidocaine
      Hydrochloride) used in castration of four to six day old male piglets. Animals of
      the control groups (I-IV) were treated analogous to the castration groups (V-IX)
      but not castrated. In groups I and V 15 minutes prior to castration/fixation the
      piglets were fixed as for injection but not medicated. The injection volume was
      standardised to 0.5 ml per testes. Local anaesthetics were applicated
      intratesticularly in five groups and intrascrotarly in two groups. Blood samples
      were taken shortly before and one, four and 24 hours after castration/fixation.
      The serum cortisol level was analysed to determine pain induced neuroendocrine
      stress reaction. To proof the tissue tolerance creatinkinase-(CK) and
      aspartataminotransferase-(AST) concentration were analysed. One, seven and 14
      days after castration the healing process were evaluated by a wound score. Groups
      I to IV did not show any increase of the serum cortisol level. Contrary one hour
      after castration the average cortisol concentration of castration groups (V-IX)
      rose significantly. Cortisol concentration of the medicated castration groups (VI
      IX) showed a comparable or even higher cortisol level as the not medicated
      control group (V). Determination of CK and AST indicated no tissue damage of the
      application of the local anaesthetics. The administration of local anaesthetics
      prior to the castration did not have any effect on the wound healing process. The
      results of this study lead to the conclusion that injection of local anaesthetics
      show a good tissue tolerance but the call for reduction of the castration pain by
      presurgical injection of Procaine Hydrochloride or Lidocaine Hydrochloride is not
      justified.

PMID- 18077933
TI  - Pacheco's parrot disease in macaws of the Lisbon's Zoological Garden. Description
      of an outbreak, diagnosis and management, including vaccination.
AB  - The Lisbon's Zoological Garden, Portugal, has maintained for many years a large
      collection of psittacine birds without any serious health problems. Unexpectedly,
      in April 1999, a total of nine macaws died after a short period of illness.
      Clinical signs consisted mainly of anorexia, ruffled feathers and yellowish
      droppings. A herpesvirus was isolated from brain, trachea, lung, liver, spleen,
      kidney and intestine of each of the examined dead birds, confirming that all
      animals succumbed during viraemia. Serotyping of the isolate in cross
      neutralization tests with reference sera prove that the outbreak was caused by
      serotype 3 of Pacheco's parrot disease herpesviruses. An autogenous, formalin
      inactivated vaccine with adjuvant (aluminium hydroxid gel) was prepared from one
      of the isolates and injected intramuscularly 14 days and six weeks after the
      onset of mortality in an attempt to protect the remaining psittacine birds in the
      zoo from the disease. The autogenous vaccine was well tolerated and was able to
      rapidly stop virus spread and morbidity and mortality among the psittacine birds.
      Follow-up studies demonstrate that all nine blood samples from vaccinated birds
      obtained nine month' after the second vaccination contain neutralizing
      antibodies. Twenty five month' after vaccination two out of four serum samples
      were still antibody positive. No herpesvirus was isolated from faecal samples
      nine and twenty five months after the onset of the outbreak. These data prove
      that the autogenous vaccine played a major role in containing a severe outbreak
      of Pacheco's parrot disease in a large collection of psittacine birds.

PMID- 18077934
TI  - [Phenotypic and genetic variation in hematological traits of Pietrain-Meishan-F2
      crossbred pigs].
AB  - Hematological traits are essential parameters for veterinary practice to quantify
      health status of individuals and herds. A major problem with the interpretation
      of hematological values is their pronounced variability that is to a great extend
      caused by non-systematic factors. Differences in breeds and populations are
      providing evidence for different genotypes in this regard, although there is no
      information available in swine about the nature and shares of participating
      genes. Goal of the present paper was to evaluate the additive-genetic share of
      total variability of traits of the red and white blood cell count. The results
      are based on 139 F2-pigs of a Pietrain-Meishan-family. Medium to high
      heritabilities have been estimated for the numbers of neutrophiles, the mean
      corpuscular hemoglobin concentration and the hemoglobin content, and for the
      shares of basophile granulocytes, platelets and lymphocytes. No meaningful shares
      of additive genetic variance were obvious in the other traits. Shares of additive
      genetic variance of the above mentioned traits argue for the existence of
      favourable and unfavourable gene variants to be involved in their phenotypic
      variation. Isolation of these variants might improve the diagnostical use of
      those traits in the future and provide a measure to advance general health in the
      pig.

PMID- 18077935
TI  - Reducing the in-vitro electromagnetic field effect of cellular phones on human
      DNA and the intensity of their emitted radiation.
AB  - Several studies have demonstrated detrimental effects of cellular phone radiation
      on in-vitro biological systems. This article introduces a novel in-vitro method
      for demonstrating conformational changes in human DNA induced by a 5 minute
      exposure to cellular phone radiation emitted by an actual contemporary cellular
      phone. Dynamic changes in DNA conformation was determined in real-time by
      measuring the rate of DNA rewinding (in a spectrophotometer) following exposure
      to heat which causes the unwinding of the two strands of the helix. Cellular
      phone radiation produced a 40% increase in the rate of DNA rewinding. This effect
      was 95% attenuated when the experiment was repeated with the same cellular phone
      to which was attached a commercially available shielding disk shaped sheet
      containing a paramagnetic mineral. In a separate series of experiments the
      intensity of the cellular phone radiation was measured using an electromagnetic
      frequency spectrum analyzer. The intensity was reduced by approximately 50% in
      the presence of the shielding disk. Taken together these studies indicate the
      efficacy of a shielding disk to protect the body from cellular phone radiation.

PMID- 18077936
TI  - Anxiety control of dental patients by clinical combination of acupuncture, Bi
      Digital O-Ring Test, and eye movement desensitization with sedation via
      submucosal route.
AB  - The data presented in this article was collected after reviewing clinical
      findings gathered from using various anxiety control methods on apprehensive
      patients. We examined clinical applications of the eye movement (EM) component of
      Eye Movement Desensitization (EMD) on fearful dental patients who have histories
      of traumatic dental experiences. We also used Bi-Digital O-Ring Test (BDORT) to
      select the proper dosage of sedative to minimize the adverse side effects. For
      patients who did not respond well to EM, we used BDORT to select the proper
      sedative medication and its dosage. In certain difficult cases, we supplemented
      these techniques with acupuncture to augment the sedative effects. Findings were
      based on the clinical impressions and assessments of both the patients and the
      operating team. Results showed that EM, although effective in enabling patients
      to undergo non-invasive dental procedures such as clinical examination and simple
      prophylaxis, had only limited beneficial effect with invasive procedures such as
      extraction, drilling, and injections, etc. We also found that BDORT greatly
      reduced adverse side effects of sedatives such as hypertension, hypotension,
      hypoxia, tachycardia, bradycardia, nausea, and vomiting. For most apprehensive
      patients, we found that EMD and acupuncture combined with BDORT predetermined
      dosage for the submucosal sedation enabled these patients to undergo the complete
      dental treatment. The authors try to explain the mechanism of BDORT and EM in
      terms of visual awareness (or consciousness) and preferred patterns, where
      neurons in the brain respond to the actions and/or direction of movement. The
      authors believe that BDORT and EM could have better results if the persons
      performing BDORT have visual awareness and are focused on the task; whereas in
      EM, the patient's eye on the therapist's hand movements. A more focused approach
      via visual pathway will result in more favorable results in EM. Likewise,
      performing BDORT absentmindedly could lead to false results if visual awareness
      (or consciousness) is absent. "Preferred pattern" will arouse neurons in the
      brain to cause conscientiousness, and performing BDORT with 'open eyes' arouse
      the necessary visual awareness that is necessary for the successful performance
      of BDORT tasks.

PMID- 18077937
TI  - Anatomical relationship between traditional acupuncture point ST 36 and Omura's
      ST 36 (True ST 36) with their therapeutic effects: 1) inhibition of cancer cell
      division by markedly lowering cancer cell telomere while increasing normal cell
      telomere, 2) improving circulatory disturbances, with reduction of abnormal
      increase in high triglyceride, L-homocystein, CRP, or cardiac troponin I & T in
      blood by the stimulation of Omura's ST 36--Part 1.
AB  - Using Bi-Digital O-Ring Test Resonance Phenomena between 2 identical substances,
      Omura, Y. succeeded in making the image of the outline of internal organs without
      use of standard imaging devices since 1982. When he imaged the outline of the
      stomach on the abdominal wall, a number of the lines came out from upper and
      lower parts of stomach wall. When the lines were followed, they were very close
      to the well-known stomach meridians. Subsequently, he found a method of
      localizing meridians and their corresponding acupuncture points as well as shapes
      and diameters accurately. At the anatomical location of ST 36 described in
      traditional textbooks, Omura, Y. found there is no acupuncture point. However, in
      the close vicinity, there is an acupuncture point which he named as true ST 36 in
      the mid 1980s, but it is generally known as Omura's ST 36. When the effects of
      the acupuncture on these 2 locations were compared, Omura's ST 36 (true ST 36)
      produced very significant well-known acupuncture beneficial effects including
      improved circulation and blood chemistry, while in the traditional ST 36, the
      effects were small. In this article, the anatomical relationship between these
      two acupuncture points, with a short distance of 0.6 approximately 1.5 cm between
      the centers of these locations, was described. In early 2000, Omura, Y. found
      Press Needle Stimulation of Omura's ST 36, using "Press-Release" procedure
      repeated 200 times, 4 times a day to cancer patients reduced high cancer cell
      telomere of 600-1500ng and high Oncogen C-fos Ab2 and Integrin alpha5beta1 of 100
      700ng BDORT units to close to lyg (= 10(-24) g) BDORT units. In addition there
      was a significant reduction of Asbestos and Hg from cancer cells, while markedly
      reduced normal cell telomere of lyg was increased to optimally high amounts of
      500-530ng BDORTunits. Thus, cancer cells can no longer divide and cancer activity
      is inhibited. The authors have successfully applied this method for a variety of
      cancers as well as for cardio-vascular diseases with hypertriglyceridemia,
      hyperglycemia, high L-homocystein, and CRP, high cardiac Troponim I & T, and some
      hypertension. These beneficial effects were accompanied by euphoria, & relaxation
      with increased alpha waves in EEG. Thus Omura's ST 36 stimulation is a safe,
      effective and highly desirable supplemental treatment. In addition to manual
      stimulation, similar beneficial effects can be induced by finger tip stmulation
      (without any needle) or with electroacupuncture stimulation, (+) Qi Gong energy
      stored paper and (+) solar energy stored paper which often resulted in
      significant clinical improvement.

PMID- 18077938
TI  - Comparison of the effectiveness of the traditional acupuncture point, ST. 36 and
      Omura's ST.36 Point (True ST. 36) needling on the isokinetic knee extension &
      flexion strength of young soccer players.
AB  - The purpose of this study was to compare the effects of the Traditional
      acupuncture point ST.36 and 'Omura's ST.36 Point' ("True ST.36") needling on the
      isokinetic knee extension & flexion strength of young soccer players. The Bi
      Digital O-Ring Test (B.D.O.R.T.) of Yoshiaki Omura, M.D.,Sc.D. was used to
      determine the "True ST.36". Young soccer players (N = 24) between 16-18 years of
      age (Mean = 16.92 +/- 0.65) were involved in the study. The extension & flexion
      strengths of dominant legs were measured with Cybex 350 Extremity System
      isokinetically. The testing velocity was 60 degrees/sec. The peak torque value in
      Newton meters (Nm) was evaluated. Subjects were tested 3 times. Extension &
      Flexion 1 (EXT1, FLEX1) without acupuncture application, EXT2 & FLEX2 after
      application on the traditional acupuncture point, ST.36 and EXT3 & FLEX3 after
      application onto the 'Omura's New Foot-point' ("True ST.36"). Before each test,
      subjects warmed up for 10 minutes by cycling on an isokinetic ergometer at 50
      RPM, 75 Watts load followed by stretching exercises of lower extremity. Mean
      EXT1, EXT2, EXT3 values were 196.92 +/- 28.70: 210.00 +/- 23.00; 224.42 +/- 21.70
      respectively, where FLEX1, FLEX2, FLEX3 were 140.88 +/- 22.45; 151.13 +/- 21.27;
      161.00 +/- 22.23. Comparisons of EXT1-EXT2, EXT1-EXT3, EXT2-EXT3, FLEX1-FLEX2,
      FLEX1-FLEX3, FLEX2-FLEX3 strength values showed all very high significance (P <
      0.001) in favor of 1) Needling on relevant points and 2) Omura's ST.36 Point
      ("True ST.36"). We conclude that B.D.O.R.T. can help to determine new (True)
      Acupuncture points and, both points were effective for increasing the isokinetic
      knee extension & flexion strength of young soccer players very significantly
      where as Omura's ST.36 Point ("True ST.36") was more effective than Traditional
      Acupuncture point, ST.36.

PMID- 18077939
TI  - Depth of penetration of an 850nm wavelength low level laser in human skin.
AB  - Low Level Laser Therapy is used for a wide variety of conditions including
      superficial skin sores, musculoskeletal and joint problems, and dentistry.
      Knowledge of the penetration depth of laser radiation in human skin is an
      essential prerequisite to identifying its method of action. Mathematical
      simulations and estimates from the literature suggest that the depth of
      penetration of laser radiation using wavelengths from 630nm up to 1100nm may be
      up to 50mm. The aim of this study is to directly measure the penetration depth of
      a Low Level Laser in human tissue. Human abdominal skin samples up to 0.784mm
      thickness were harvested by dermatome following abdominoplasty procedures. These
      samples were irradiated by a Gallium Aluminium Arsenide Laser (Wavelength 850nm
      near infra-red invisible light, 100mW, 24kHz, 0.28mm diameter probe) and the
      transmitted radiation measured with an Ophir Optronics 'Nova' external energy
      meter. The intensity of laser radiation reduced by 66% after being transmitted
      through a 0.784mm sample of human abdominal tissue. In this study most laser
      radiation was absorbed within the first 1mm of skin.

PMID- 18077940
TI  - How to standardize 3 finger positions of examiner for palpating radial pulses at
      wrist in traditional Chinese medicine.
AB  - This study was to provide a standardized definition of the positioning method of
      finger placement on the radial artery for pulse diagnosis in traditional Chinese
      medicine (TCM); that is, to define the locations of Cun, Guan and Chi in TCM. A
      total of 200 subjects (100 males and 100 females, 18-40 years of age) were
      recruited from the general population. According to ancient TCM records, the "6%
      of the elbow length" (ELx6%) is used as the standard method of establishing the
      length of Cun. We hypothesized that the highest point of "prominent bone" (PB) is
      the lower limit of Cun, so "the distance between the distal wrist crease and the
      highest point of the PB" (DWP) is considered the length of Cun. If this
      hypothesis holds, then we can define the locations of Cun, Guan and Chi by using
      the ratio 6:6:7 from the ancient TCM records. The distribution of relative bias
      and paired t-test were used to verify the findings. The mean value of relative
      bias of DWP compared with ELx6% was close to 0% (males = 2.1%, SD = 12.2%;
      females = 0.2%, SD = 12.6%). The paired t-test confirmed that there was no
      significant difference (p > 0.05) between the mean values of the DWP and ELx6%.
      Therefore, it is reasonable to assume that the length of the Cun is equal to the
      length of the DWP. Our findings confirm that the location of Cun is from the
      distal wrist crease to the highest point of PB.

PMID- 18077941
TI  - Naval aviation and neurosurgery: traditions, commonalities, and lessons learned.
      The 2007 presidential address.
AB  - In his presidential address to the American Association of Neurological Surgeons,
      the author recounts lessons he learned while training to be a Naval Aviator and
      later a neurosurgeon. He describes his life as an aviator and neurosurgeon,
      compares naval aviation and neurosurgery, and points out lessons that
      neurosurgery can learn from naval aviation.

PMID- 18077942
TI  - Early ischemic lesion on computed tomography: predictor of poor outcome among
      survivors of aneurysmal subarachnoid hemorrhage.
AB  - OBJECT: Identifying ischemic lesions after subarachnoid hemorrhage (SAH) is
      important because the appearance of these lesions on follow-up imaging correlates
      with a poor outcome. The effect of ischemic lesions seen on computed tomography
      (CT) scans during the first days of treatment remains unknown, however. METHODS:
      In 156 patients with SAH, clinical course and outcome, as well as the appearance
      of ischemic lesions on serial CT scans, were prospectively monitored for 3
      months. At 3 months after SAH, magnetic resonance imaging was performed to detect
      permanent lesions that had not been visible on CT. RESULTS: Of the 53 patients
      with no lesions on any of the follow-up CT scans, four (8%) had a poor outcome.
      Of the 52 patients with a new hypodense lesion on the first postoperative day CT,
      23 (44%) had a poor outcome. Among the remaining 51 patients with a lesion
      appearing later than the first postoperative morning, 10 (20%) had a poor outcome
      (p < 0.001). After adjusting for patient age; clinical condition on admission;
      amounts of subarachnoid, intracerebral, and intraventricular blood; and plasma
      glucose and D-dimer levels, a hypodense lesion on CT on the first postoperative
      morning was an independent predictor of poor outcome after SAH (odds ratio 7.27,
      95% confidence interval 1.54-34.37, p < 0.05). CONCLUSIONS: A new hypodense
      lesion on early postoperative CT seems to be an independent risk factor for poor
      outcome after SAH, and this early lesion development may be more detrimental to
      clinical outcome than a later lesion occurrence.

PMID- 18077943
TI  - Persistent perioperative hyperglycemia as an independent predictor of poor
      outcome after aneurysmal subarachnoid hemorrhage.
AB  - OBJECT: The authors of previous studies have shown that admission hyperglycemia
      or perioperative hyperglycemic events may predispose a patient to poor outcome
      after aneurysmal subarachnoid hemorrhage (SAH). The results of experimental
      evidence have suggested that hyperglycemia may exacerbate ischemic central
      nervous system injury. It remains to be clarified whether a single hyperglycemic
      event or persistent hyperglycemia is predictive of poor outcome after aneurysmal
      SAH. METHODS: Ninety-seven patients undergoing treatment for aneurysmal SAH were
      observed, and all perioperative variables were entered into a database of
      prospectively recorded data. Daily serum glucose values were retrospectively
      added. Patients were examined at hospital discharge (14-21 days after SAH onset),
      and Glasgow Outcome Scale (GOS) scores were prospectively documented. The GOS
      score at last follow-up was retrospectively determined. Serum glucose greater
      than 200 mg/dl for 2 or more consecutive days was defined as persistent
      hyperglycemia. Outcome was categorized as "poor" (dependent function [GOS Score 1
      3]) or "good" (independent function [GOS Score 4 or 5]) at discharge. The
      independent association of 2-week and final follow-up outcome (GOS score) with
      the daily serum glucose levels was assessed using a multivariate analysis.
      RESULTS: In the univariate analysis, increasing age, increasing Hunt and Hess
      grade, hypertension, ventriculomegaly on admission computed tomography scan,
      Caucasian race, and higher mean daily glucose levels were associated with poor
      (dependent) 2-week outcome after aneurysmal SAH. In the multivariate analysis,
      older age, the occurrence of symptomatic cerebral vasospasm, increasing admission
      Hunt and Hess grade, and persistent hyperglycemia were independent predictors of
      poor (dependent) outcome 2 weeks after aneurysmal SAH. Admission Hunt and Hess
      grade and persistent hyperglycemia were independent predictors of poor outcome at
      last follow-up examination a mean 10 +/- 3 months after aneurysmal SAH. Isolated
      hyperglycemic events did not predict poor outcome. Patients with persistent
      hyperglycemia were 10-fold more likely to have a poor (dependent) 2-week outcome
      and sevenfold more likely to have a poor outcome a mean 10 months after
      aneurysmal SAH independent of admission Hunt and Hess grade, occurrence of
      cerebral vasospasm, or all comorbidities. CONCLUSIONS: Patients with persistent
      hyperglycemia were seven times more likely to have a poor outcome at a mean of 10
      months after aneurysmal SAH. Isolated hyperglycemic events were not predictive of
      poor outcome. Serum glucose levels in the acute setting of aneurysmal SAH may
      help predict outcomes months after surgery.

PMID- 18077944
TI  - Postoperative quality of life of patients treated for asymptomatic unruptured
      intracranial aneurysms.
AB  - OBJECT: The aim of this study was to assess the quality of life (QOL) of patients
      who underwent surgery for asymptomatic unruptured intracranial aneurysms (UIAs).
      METHODS: The authors assessed QOL in 149 patients who had undergone microsurgical
      clipping of asymptomatic UIAs. They surveyed these patients using universal
      methods such as the 36-Item Short Form Health Survey (SF-36) for health-related
      QOL and the Hospital Anxiety and Depression Scale for anxiety and depression
      assessments. RESULTS: The patients' mean scores for each of the eight domains of
      SF-36 were comparable to those of a Japanese reference population. Analysis of
      data from the average-QOL and low-QOL subgroups showed that the low-QOL group
      contained a higher number of patients with preexisting heart diseases and
      restricted activities of daily living. Operative procedures and complications did
      not affect QOL. CONCLUSIONS: Because 86% of the patients who underwent surgery
      manifested a QOL similar to the reference population, the authors suggest that
      elective surgery for asymptomatic UIAs is a reasonable treatment, especially in
      patients who are troubled by the risk of rupture. Postoperative decreases in QOL
      are not invariably attributable to the operation or its associated complications,
      but may be correlated with other chronic disorders. To select the appropriate
      treatment for asymptomatic UIAs, neurosurgeons and patients need information on
      the expected postoperative QOL.

PMID- 18077945
TI  - Biological effects of acute pravastatin treatment in patients after aneurysmal
      subarachnoid hemorrhage: a double-blind, placebo-controlled trial.
AB  - OBJECT: The authors previously demonstrated that acute pravastatin therapy in
      patients after aneurysmal subarachnoid hemorrhage (SAH) ameliorates vasospasm
      related delayed ischemic neurological deficits. The object of this study was to
      continue to examine potential mechanisms of these beneficial effects. METHODS:
      Eighty patients with aneurysmal SAH (age range 18-84 years; time to onset 1.8 +/-
      1.3 days) were enrolled in a double-blind study and randomized to receive 40 mg
      of oral pravastatin or placebo daily for as long as 14 days. Daily transcranial
      Doppler ultrasonography and blood tests every 3 days (including full blood cell
      counts, coagulation profiles, fasting glucose and lipid profiles, and serum
      biochemistry) were performed during the trial period. RESULTS: No significant
      differences were found in baseline laboratory data between the trial groups.
      Subsequent measurements during the 14-day trial showed reduced low-density
      lipoprotein (LDL) cholesterol levels and total/high-density lipoprotein
      cholesterol ratios between Days 3 and 15 (p < 0.05), and increased D-dimer levels
      (p < 0.05) on Day 6, in the pravastatin group. Patients who received pravastatin
      but developed vasospasm had significantly lower baseline LDL cholesterol levels
      or a less extensive reduction in LDL cholesterol levels (p < 0.05), and greater
      increases in plasma fibrinogen (p = 0.009) and serum C-reactive protein on Day 3
      (p = 0.007), compared with those patients without vasospasm. The reduction in LDL
      cholesterol levels on Day 3 in the placebo group correlated with the duration of
      normal cerebral autoregulation on the ipsilateral side of the ruptured aneurysm
      (p = 0.002). CONCLUSIONS: In addition to functioning through a cholesterol
      independent pathway, cerebrovascular protection from acute statin therapy
      following aneurysmal SAH may also function through cholesterol-dependent
      mechanisms.

PMID- 18077946
TI  - Vasospasm probability index: a combination of transcranial doppler velocities,
      cerebral blood flow, and clinical risk factors to predict cerebral vasospasm
      after aneurysmal subarachnoid hemorrhage.
AB  - OBJECT: The goal in this study was to create an index (vasospasm probability
      index [VPI]) to improve diagnostic accuracy for vasospasm after subarachnoid
      hemorrhage (SAH). METHODS: Seven hundred ninety-five patients in whom aneurysmal
      SAH was demonstrated by computed tomography, and in whom one or more intracranial
      aneurysms had been diagnosed, underwent transcranial Doppler (TCD) studies
      between April 1998 and January 2000. In 154 patients angiography was performed
      within 24 hours of the TCD examination, and in 75 133Xe cerebral blood flow (CBF)
      studies were obtained the same day. Seven cases were excluded because of a
      limited sonographic window. Forty-one women (60.3%) and 27 men (39.7%) between
      the ages of 35 and 84 years (58.0 +/- 13.2 years [mean +/- standard deviation])
      were included. Clinical characteristics analyzed included age, sex, Hunt and Hess
      grade, Fisher grade, days after SAH, day of treatment, type of treatment (coil
      embolization, surgical clip occlusion, or conservative treatment), smoking
      history, and hypertension history. Lindegaard ratios and spasm indexes (TCD
      velocities/hemispheric CBF) were calculated bilaterally. Digital subtraction
      angiography images were measured at specific points of interest. Sensitivity,
      specificity, predictive values, and global accuracy of the different tests were
      calculated. Logistic regression was used to evaluate the possible predictive
      factors, and the coefficients of the logistic regression were integrated to
      create the VPI. RESULTS: In 18 patients (26.5%) symptomatic vasospasm was
      diagnosed, and 33 (48.5%) had angiographic evidence of vasospasm. For TCD
      velocities above 120 cm/second at the middle cerebral artery, the global accuracy
      was 81.1% for the diagnosis of clinical vasospasm and 77.2% for angiographic
      vasospasm. For a Lindegaard ratio higher than 3.0, the accuracy was 85% for
      clinical vasospasm and 83.2% for angiographic vasospasm. A spasm index higher
      than 3.5 had an accuracy of 82.0% for the diagnosis of clinical vasospasm and
      81.6% for angiographic vasospasm. The selected model for estimation of clinical
      vasospasm included Fisher grade, Hunt and Hess grade, and spasm index. The VPI
      had a global accuracy of 92.9% for clinical vasospasm detection. For diagnosis of
      angiographic vasospasm, the model included Fisher grade, Hunt and Hess grade, and
      Lindegaard ratio. The VPI achieved a global accuracy of 89.9% for angiographic
      vasospasm detection. CONCLUSIONS: The use of TCD velocities, Lindegaard ratio,
      and spasm index independently is of limited value for the diagnosis of clinical
      and angiographic vasospasm. The combination of predictive factors associated with
      the development of vasospasm in the new index reported here has a significantly
      superior accuracy compared with the independent tests and may become a valuable
      tool for the clinician to evaluate the individual probability of cerebral
      vasospasm after aneurysmal SAH.

PMID- 18077947
TI  - The neurovascular triad: mixed cavernous, capillary, and venous malformations of
      the brainstem.
AB  - OBJECT: The four types of cerebrovascular malformations may sometimes be combined
      and more often occur in pairs; triads are exceptional. The authors present six
      patients with the clinicoradiographic profile of mixed vascular malformations of
      the brainstem, including cavernous malformation (CM), capillary telangiectasia,
      and developmental venous anomaly (DVA). METHODS: Five patients (one of whom was a
      child) suffered from hemorrhage, suggesting that this complex association has a
      high bleeding potential. Progressive growth, rebleeding, and de novo occurrence
      of the associated CM were documented in three cases. Magnetic resonance imaging
      of the brain was obtained in all patients by using one or more of the following
      modalities: T1-weighted sequences before and after gadolinium administration; T2
      weighted sequences; T2-weighted fluid attenuated Inversion recovery; T1-weighted
      fast spin echo; and diffusion weighted, diffusion tensor, and perfusion imaging
      in three cases. RESULTS: Three patients were surgically treated with the
      intention of excising the hemorrhagic lesion, but only two patients had their
      malformations successfully removed. In the third case, diffuse pontine
      telangiectasia precluded the safe excision of the CM. Histological examination
      demonstrated a blended pathological milieu characterized by coalescent
      telangiectasia and venules associated with loculated endothelial chambers
      resembling an immature or de novo CM. Three patients were treated conservatively;
      recurrent minor hemorrhage occurred in one case. The authors found these
      malformations to be arranged in two basic relationships: CM inside the
      telangiectasia and CM in the radicles of the DVA. Stenosis of the main venous
      collector and dilation of the medullary veins were important findings.
      CONCLUSIONS: The pathogenesis of this malformation may be referred to a
      developmental deviance of the brainstem capillary-venous network associated with
      transitional vessels and loculated endothelial vascular spaces related to genetic
      and acquired origins, probably in a restrictive venous outflow milieu.

PMID- 18077948
TI  - Treatment of dural arteriovenous fistula using ethylene vinyl alcohol (onyx)
      arterial embolization as the primary modality: short-term results.
AB  - OBJECT: A dural arteriovenous fistula (DAVF) typically involves meningeal feeding
      arteries and can cause clinical symptoms ranging from tinnitus to rupture of
      draining cortical or parenchymal veins. Surgical treatment may be technically
      demanding. Ethylene vinyl alcohol (Onyx, ev3 Neurovascular) has several
      properties that make it potentially useful as a primary treatment agent for DAVF.
      Onyx is expected to be a permanent embolic agent. It should have a decreased risk
      of catheter retention when compared with other permanent embolic materials.
      METHODS: The authors report a series of six patients with symptomatic DAVF who
      were treated initially with transarterial Onyx embolization and other
      endovascular techniques. RESULTS: Five patients had complete occlusion of their
      DAVF noted on the follow-up angiogram obtained between 2 and 4 months. One
      patient had residual filling via a small arterial branch that was stable on
      follow-up angiography. None of the patients had worsening of neurological
      function. One case was complicated by a retained catheter fragment. CONCLUSIONS:
      Transarterial Onyx embolization and other endovascular methods can
      angiographically obliterate DAVF. In some cases, embolization allowed occlusion
      of multiple arterial feeding arteries from a single arterial injection.
      Technically, the embolization was optimized when a microcatheter position
      immediately adjacent to the point(s) of fistulization was achieved.

PMID- 18077949
TI  - Evaluation of olfactory nerve function after aneurysmal subarachnoid hemorrhage
      and clip occlusion.
AB  - OBJECT: In this study, the olfactory nerve function (ONF) in patients with an
      aneurysmal subarachnoid hemorrhage (SAH) who underwent neurosurgical clip
      occlusion for intracranial aneurysm was assessed pre- and postoperatively.
      METHODS: In 13 patients with an aneurysmal SAH who underwent a frontobasal or
      frontotemporal neurosurgical procedure for clipping of a ruptured intracranial
      aneurysm, ONF was assessed pre- and postoperatively by using a standardized
      olfactory test battery ("Sniffin' Sticks"). Preoperative testing was performed
      within the first 72 hours after SAH. For their follow-up visit, patients were
      tested 3 months after surgery. Olfactory thresholds, odor discrimination, and
      odor identification were documented. Only cooperative patients were included, and
      as a result, all patients enrolled in the study were classified in Hunt and Hess
      Grade II. RESULTS: After SAH and before surgery, three patients were normosmic,
      seven were hyposmic, and three were anosmic according to the Sniffin' Sticks
      test. Thus, 10 of 13 patients with SAH already showed disturbance of ONF
      preoperatively. Of these 10, however, only two patients experienced reduced smell
      and taste sensation. At the 3-month follow-up review, 10 patients could be
      tested. Three normosmic patients remained normosmic. In one patient, ONF had
      improved from anosmic to hyposmic, whereas in another patient, ONF had worsened
      from hyposmic to anosmic. Thus, in eight patients, ONF remained unchanged after
      surgery. Three patients reported disturbed smell and/or taste sensation. One
      anosmic patient had experienced no smell sensation since surgery; however, he
      reported his taste to be normal. Another hyposmic patient experienced both
      reduced smell and taste sensation. One normosmic patient reported normal smelling
      ability but disturbed taste sensation. CONCLUSIONS: This study provides evidence
      that aneurysmal SAH causes disturbance of ONF in a substantial number of cases.
      With the exception of one case, neurosurgical treatment did not alter a
      preexisting olfactory deficit. Improvement of SAH-induced olfactory dysfunction
      at follow-up, however, can also be documented. The subjective assessments of the
      patients do not correspond well with the test battery results.

PMID- 18077950
TI  - Intracranial hemorrhage associated with cerebral hyperperfusion syndrome
      following carotid endarterectomy and carotid artery stenting: retrospective
      review of 4494 patients.
AB  - OBJECT: Intracranial hemorrhage associated with cerebral hyperperfusion syndrome
      (CHS) following carotid endarterectomy (CEA) or carotid artery stenting (CAS) is
      a rare but potentially devastating complication. In the present study the authors
      evaluated 4494 patients with carotid artery stenosis who had undergone CEA or CAS
      to clarify the clinicopathological features and outcomes of those with CHS and
      associated intracranial hemorrhage. METHODS: Patients with postoperative CHS were
      retrospectively selected, and clinicopathological features and outcomes were
      studied. RESULTS: Sixty-one patients with CHS (1.4%) were identified, and
      intracranial hemorrhage developed in 27 of them (0.6%). The onset of CHS peaked
      on the 6th postoperative day in those who had undergone CEA and within 12 hours
      in those who had undergone CAS. Results of logistic regression analysis
      demonstrated that poor postoperative control of blood pressure was significantly
      associated with the development of intracranial hemorrhage in patients with CHS
      after CEA (p = 0.0164). Note, however, that none of the tested variables were
      significantly associated with the development of intracranial hemorrhage in
      patients with CHS after CAS. Mortality (p = 0.0010) and morbidity (p = 0.0172)
      rates were significantly higher in patients with intracranial hemorrhage than in
      those without. CONCLUSIONS: Cerebral hyperperfusion syndrome after CEA and CAS
      occurs with delayed classic and acute presentations, respectively. Although
      strict control of postoperative blood pressure prevents intracranial hemorrhage
      in patients with CHS after CEA, there appears to be no relationship between blood
      pressure control and intracranial hemorrhage in those with CHS after CAS.
      Finally, the prognosis of CHS in patients with associated intracerebral
      hemorrhage is poor.

PMID- 18077951
TI  - Intraoperative three-dimensional visualization in microvascular decompression.
AB  - OBJECT: The authors systematically analyzed 3D visualization of neurovascular
      compression (NVC) syndromes in the operating room (OR) during microvascular
      decompression (MVD). METHODS: A total of 50 patients (26 women and 24 men) with
      trigeminal neuralgia (TN), hemifacial spasm (HFS), and glossopharyngeal neuralgia
      (GN) were examined and underwent MVD. Preoperative imaging of the neurovascular
      structures was performed using constructive interference in the steady state
      magnetic resonance (CISS MR) imaging, which consisted of 2D image slices. The 3D
      visualization of the neurovascular anatomy is generated after segmentaion of the
      CISS MR imaging in combination with direct volume rendering (DVR). The 3D
      representations were stored on a personal computer (PC) that was mounted on a
      mobile unit and transferred to the OR. During surgery, 3D visualization was
      applied by the surgeon with remotely controlled plasma-sterilized devices such as
      a wireless mouse and keyboard. The position of the 3D visualized neurovascular
      structures at the PC monitor was determined according to the intraoperative
      findings observed through the operating microscope. RESULTS: The system was
      stable during all neurosurgical procedures, and there were no operative or
      technical complications. Interactive adjustment of the 3D visualization guided by
      the view through the microscope permitted observation of the neurovascular
      relationships at the brainstem. Vessels covered by the cranial nerves could be
      noninvasively viewed by intraoperative 3D visualization. Postoperatively, the
      patients with TN and GN experienced pain relief, and the patients with HFS
      attained resolution of their facial tics. Vascular compression of nerves was
      explored in all 50 patients during MVD. Intraoperative 3D visualization
      delineated the compressing vessels and respective cranial nerves in 49 (98%) of
      50 patients. CONCLUSIONS: Interactive 3D visualization by DVR of high-resolution
      MR imaging data offered the opportunity for noninvasive virtual exploration of
      the neurovascular structures during surgery. An extended global survey of the
      neurovascular relationships was provided during MVD in each case. The presented
      method proved to be extremely advantageous for optimizing microneurosurgical
      procedures, supporting superior safety and improving the operative results when
      compared with the conventional strategy. This modality proved to be a very
      valuable teaching instrument and ensured the improvement of neurosurgical
      quality.

PMID- 18077952
TI  - Microvascular decompression for primary trigeminal neuralgia: long-term
      effectiveness and prognostic factors in a series of 362 consecutive patients with
      clear-cut neurovascular conflicts who underwent pure decompression.
AB  - OBJECT: The purpose of this study was to evaluate the long-term efficacy of
      microvascular decompression (MVD) and to identify the factors affecting outcome
      in patients treated for primary trigeminal neuralgia (TN). Only the cases with a
      clear-cut neurovascular conflict (vascular contact and/or compression of the root
      entry zone of the trigeminal nerve) found at surgery and treated with "pure" MVD
      (decompression of the root without any additional lesioning or cutting of the
      adjacent rootlets) were retained. METHODS: The study included 362 patients who
      were followed up over a period of 1 to 18 years (median follow-up 7.2 years). A
      Kaplan-Meier survival analysis was generated at 1 and 15 years of follow-up for
      all of the considered factors. According to Kaplan-Meier analysis, the success
      rate (defined as pain-free patients without any medication) was 91% at 1 year and
      estimated to be 73.38% after 15 years of follow-up. RESULTS: None of the
      following patient-related factors played any significant role in prognosis: sex,
      patient age at surgery, history of systemic hypertension, duration of neuralgia
      before surgery, or history of failed trigeminal surgery. Patients with atypical
      neuralgia (a baseline of permanent pain) had the same outcome as those with a
      typical (purely spasmodic) presentation. In addition, the side and topography of
      the trigeminal nerve did not play a role, whereas involvement of all three
      divisions of the nerve had a negative effect on outcome. Concerning anatomical
      factors, neither the type of the compressive vessel nor its location along or
      around the root was found to be significant. However, the severity of compression
      was important-the more severe the degree of compression, the better the outcome
      (p = 0.002). The authors also found that presence of focal arachnoiditis had a
      negative influence on outcome (p = 0.002). CONCLUSIONS: Pure MVD can offer
      patients affected by a primary TN a 73.38% probability of long-term (15 years)
      cure of neuralgia. The presence of a clear-cut and marked vascular compression at
      surgery (and possibly-although not yet reliably--on preoperative magnetic
      resonance imaging) is the guarantee of a higher than 90% success rate.

PMID- 18077953
TI  - Classification of neurovascular compression in typical hemifacial spasm: three
      dimensional visualization of the facial and the vestibulocochlear nerves.
AB  - OBJECT: In this paper, the authors introduce a method of noninvasive anatomical
      analysis of the facial nerve-vestibulocochlear nerve complex and the depiction of
      the variable vascular relationships by using 3D volume visualization. With this
      technique, a detailed spatial representation of the facial and vestibulocochlear
      nerves was obtained. Patients with hemifacial spasm (HFS) resulting from
      neurovascular compression (NVC) were examined. METHODS: A total of 25 patients
      (13 males and 12 females) with HFS underwent 3D visualization using magnetic
      resonance (MR) imaging with 3D constructive interference in a steady state
      (CISS). Each data set was segmented and visualized with respect to the individual
      neurovascular relationships by direct volume rendering. Segmentation and
      visualization of the facial and vestibulocochlear nerves were performed with
      reference to their root exit zone (REZ), as well as proximal and distal segments
      including corresponding blood vessels. The 3D visualizations were interactively
      compared with the intraoperative situation during microvascular decompression
      (MVD) to verify the results with the observed microneurosurgical anatomy.
      RESULTS: Of the 25 patients, 20 underwent MVD (80%). Microvascular details were
      recorded on the affected and unaffected sides. On the affected sides, the
      anterior inferior cerebellar artery (AICA) was the most common causative vessel.
      The posterior inferior cerebellar artery, vertebral artery, internal auditory
      artery, and veins at the REZ of the facial nerve (the seventh cranial nerve) were
      also found to cause vascular contacts to the REZ of the facial nerve. In addition
      to this, the authors identified three distinct types of NVC within the REZ of the
      facial nerve at the affected sides. The authors analyzed the varying courses of
      the vessels on the unaffected sides. There were no bilateral clinical symptoms of
      HFS and no bilateral vascular compression of the REZ of the facial nerve. The
      authors discovered that the AICA is the most common vessel that interferes with
      the proximal and distal portions of the facial nerve without any contact between
      vessels and the REZ of the facial nerve on the unaffected sides. CONCLUSIONS:
      Three-dimensional visualization by direct volume rendering of 3D CISS MR imaging
      data offers the opportunity of noninvasive exploration and anatomical
      categorization of the facial nerve-vestibulocochlear nerve complex. Furthermore,
      it proves to be advantageous in establishing the diagnosis and guiding
      neurosurgical procedures by representing original MR imaging patient data in a 3D
      fashion. This modality provides an excellent overview of the entire neurovascular
      relationship of the cerebellopontine angle in each case.

PMID- 18077954
TI  - Endoscopically assisted decompression of the suprascapular nerve in the
      supraspinous fossa: a cadaveric feasibility study. Laboratory investigation.
AB  - OBJECT: The suprascapular nerve may become entrapped as it travels deep to the
      suprascapular ligament, necessitating decompression. The present study was
      performed to verify the feasibility of a minimally invasive, endoscopically
      assisted technique for decompressing the suprascapular nerve in the supraspinous
      fossa. METHODS: The authors performed dissection and decompression of the
      suprascapular ligament using an endoscopically assisted technique via a 3-cm skin
      incision in 10 adult cadavers (20 sides). Measurements were also made of the
      depth from the skin to the suprascapular ligament. RESULTS: A mean depth of 4 cm
      was necessary to reach the suprascapular ligament from the skin surface. With the
      authors' approach, no obvious injury occurred to the suprascapular or other
      vicinal neurovascular structures (such as the spinal accessory nerve and
      suprascapular vessels). CONCLUSIONS: The results of this cadaveric study
      demonstrate that access to the suprascapular nerve can be obtained endoscopically
      via a small suprascapular incision. This approach obviates a large incision,
      entry into the glenohumeral joint, and reduces the risk of spinal accessory nerve
      injury in the posterior cervical triangle, or atrophy of the trapezius or
      supraspinatus muscles from a standard larger dissection. To the authors'
      knowledge an endoscopically assisted approach to decompressing the suprascapular
      nerve as it courses deep to the suprascapular ligament has not been reported
      previously.

PMID- 18077955
TI  - The role of evaluation methods in the assessment of peripheral nerve regeneration
      through synthetic conduits: a systematic review. Laboratory investigation.
AB  - OBJECT: A number of evaluation methods that are currently used to compare
      peripheral nerve regeneration with alternative repair methods and to judge the
      outcome of a new paradigm were hypothesized to lack resolving power. This would
      too often lead to the conclusion that the outcome of a new paradigm could not be
      discerned from the outcome of the current gold standard, the autograft. As a
      consequence, the new paradigm would incorrectly be judged as successful. METHODS:
      An overview of the methods that were used to evaluate peripheral nerve
      regeneration after grafting of the rat sciatic nerve was prepared. All articles
      that were published between January 1975 and December 2004 and concerned grafting
      of the rat sciatic nerve (minimum graft length 5 mm) and in which the
      experimental method was compared with an untreated or another grafted nerve were
      included. The author scored the presence of statistically significant differences
      between paradigms. RESULTS: Evaluation of nerve fiber count, nerve fiber density,
      N-ratio, nerve histological success ratio, compound muscle action potential,
      muscle weight, and muscle tetanic force are methods that were demonstrated to
      have resolving power. CONCLUSIONS: A number of evaluation methods are not
      suitable to demonstrate a significant difference between experimental paradigms
      in peripheral nerve regeneration. It is preferable to apply a combination of
      evaluation methods with resolving power to evaluate nerve regeneration properly.

PMID- 18077956
TI  - Sutureless nonocclusive bypass surgery in combination with an expanded
      polytetrafluoroethylene graft. Laboratory investigation.
AB  - OBJECT: Cerebral aneurysms that cannot be treated by clip or coil placement can
      be treated with high-flow bypass surgery using techniques such as the excimer
      laser-assisted nonocclusive anastomosis (ELANA). To simplify the technique, a
      sutureless ELANA (SELANA) was developed in combination with an expanded
      polytetrafluoroethylene (ePTFE) graft. METHODS: In 18 rabbits a bypass was
      constructed on the abdominal aorta using the SELANA technique with an ePTFE
      graft, resulting in 18 bypasses and 36 anastomoses. Short-term effects were
      analyzed in the first 2 weeks and at 2 and 3 months after the procedure. Patency
      was evaluated using quantitative ultrasound flowmetry. The anastomotic sites were
      studied using scanning electron microscopy. RESULTS: Construction of the bypass
      using the SELANA technique was easier and faster (15-25 minutes) compared with
      bypasses made with the ELANA technique (> 90 minutes). At the end of follow-up,
      16 of 18 bypasses were patent. Of 36 SELANA anastomoses, 32 could be completed
      without short temporary occlusion of the recipient vessel. Scanning electron
      microscopy showed complete coverage of all anastomoses with neointimal repair
      tissue after 10 days. CONCLUSIONS: The SELANA technique provides further
      advantages over the conventional ELANA technique in ease of use and shortening of
      procedure time. The patency rate in this series was 89% and neointima repair
      tissue at the anastomosis site was complete after 10 days. Further experimental
      studies of the long-term patency and safety of this technique are necessary
      before clinical application.

PMID- 18077957
TI  - Prototypical metal/polymer hybrid cerebral aneurysm clip: in vitro testing for
      closing force, slippage, and computed tomography artifact. Laboratory
      investigation.
AB  - OBJECT: The aim of this study was to explore the possibility that a hybrid
      aneurysm clip with polymeric jaws bonded to a metal spring could provide
      mechanical properties comparable to those of an all-metal clip as well as
      diminished artifacts on computed tomography (CT) scanning. METHODS: Three clips
      were created, and Clips I and 2 were tested for mechanical properties. Clip 1
      consisted of an Elgiloy spring (a cobalt-chromium-nickel alloy) bonded to carbon
      fiber limbs; Clip 2 consisted of an Elgiloy spring with polymethylmethacrylate
      (PMMA) jaws; and Clip 3 consisted of PMMA limbs identical to those in Clip 2 but
      bonded to a titanium spring. Custom testing equipment was set up to measure the
      aneurysm clip clamping forces and slippage. Clips 2 and 3 were visualized in vivo
      using a 64-slice CT unit, and the slices were reformatted into 3D images.
      RESULTS: According to the testing apparatus, Clip 2 had a similar closing force
      but less slippage than three similar commercial aneurysm clips. The artifact from
      the cobalt alloy spring on CT scanning largely offset the advantage of the
      nonmetal PMMA limbs, which created no artifact. The hybrid titanium/PMMA clip
      (Clip 3) created very little artifact on CT and allowed visualization of the
      phantom through the limbs. CONCLUSIONS: It is feasible to build a potentially
      biocompatible hybrid cerebral aneurysm clip with mechanical properties that
      closely resemble those of conventional metallic clips. Further testing should be
      directed toward establishing the reliability and biocompatibility of such a clip
      and optimizing the contour and surface treatments of the polymer

PMID- 18077958
TI  - A hypothesis of cerebral venous system regulation based on a study of the
      junction between the cortical bridging veins and the superior sagittal sinus.
      Laboratory investigation.
AB  - OBJECT: The cerebral venous regulation involved in various physiological and
      pathological processes has received little attention. Here the authors describe
      the anatomy of the junction between the cortical vein and the superior sagittal
      sinus (SSS) and propose a new theory of cerebral venous regulation. METHODS: Ten
      adult human cadaveric heads (20 sides), including five specimens into which
      stained latex had been injected, were used for anatomical study. Formalin-fixed
      cadaver heads were dissected to demonstrate the cortical veins along the SSS. The
      characteristics of the cortical bridging veins and their openings into the SSS
      were established by anatomical, histological, immunohistochemical, and
      ultrastructural study of the junction. RESULTS: After their subarachnoid course,
      the cortical bridging veins penetrated the SSS at different points in the dura
      mater depending on their rostrocaudal position. The venous endothelium stretched
      beyond the sinus endothelium. The orientation of the collagen fibers changed at
      the level of the venous openings, with the luminal diameter becoming narrow and
      oval-shaped. The major finding was the organization of the smooth-muscle cells at
      the end of each cortical vein. At this site and particularly in the
      frontoparietal region, the vessel resembled a myoendothelial "sphincter." The
      authors hypothesize that this organization is involved in cerebral venous system
      regulation. CONCLUSIONS: The point of convergence between the cortical veins and
      the SSS is a key area. The authors also hypothesize that the myoendothelial
      junction acts as a smooth sphincter and that it plays a role in cerebral venous
      hemodynamics and pathological conditions.

PMID- 18077959
TI  - Treatment of blood blister-like aneurysm of the internal carotid artery with
      stent-assisted coil embolization followed by stent-within-a-stent technique. Case
      report.
AB  - Ruptured blood blister-like aneurysms (BBAs) of the internal carotid artery (ICA)
      are potentially dangerous lesions because of the high risk of intraoperative
      bleeding associated with their wide fragile neck. The authors discuss cases in
      which BBAs were treated endovascularly during the chronic stage and report a case
      in which a ruptured BBA of the ICA was successfully treated in the acute phase
      with stent-assisted coil embolization and a subsequent stent-within-a-stent
      procedure.

PMID- 18077960
TI  - Contralateral vertebral approach for stenting and coil embolization of a large,
      thrombosed vertebral-posterior inferior cerebellar artery aneurysm. Case report.
AB  - The authors report the successful staged stenting and coil embolization of a
      large vertebral artery-posterior inferior cerebellar artery (VA-PICA) aneurysm
      using the contralateral VA for access. A 67-year-old woman presented with a large
      ruptured VA-PICA aneurysm. Initial attempts to stent the wide-necked aneurysm
      from the ipsilateral side failed, so coil embolization of the dome was performed.
      During a second endovascular session, the aneurysm neck was successfully stented
      from the contralateral VA into the PICA. Six weeks later, coils were inserted
      into the aneurysm from the ipsilateral side. The coil result was stable at the 3
      month follow-up examination.

PMID- 18077961
TI  - External carotid artery angioplasty and stenting to augment cerebral perfusion in
      the setting of subacute symptomatic ipsilateral internal carotid artery
      occlusion. Case report.
AB  - The authors performed external carotid artery (ECA) angioplasty and stenting in a
      45-year-old man who had presented with right hemispheric crescendo ischemic
      symptoms stemming from acute right internal carotid artery occlusion (ICAO). This
      unique application of ECA angioplasty and stenting augmented cerebral perfusion
      and improved clinical symptoms. In certain situations, ECA stenting can increase
      cerebral perfusion in the setting of ICAO and ECA stenosis. The authors are the
      first to describe this approach in this context.

PMID- 18077962
TI  - "Internal cross-clamping" for symptomatic internal carotid artery thrombus.
      Report of two cases.
AB  - Both carotid endarterectomy and carotid artery stent placement with filter
      embolic protection present a higher risk for patients with internal carotid
      artery (ICA) lesions containing intraluminal thrombus. Despite the risk
      associated with intervention, patients with symptomatic intraluminal thrombus who
      were enrolled in the North American Symptomatic Endarterectomy Trial did better
      with surgical than medical treatment. We describe the novel use of an
      endovascular "internal cross-clamping" technique in two patients with symptomatic
      intraluminal thrombus in the ICA. A 57-year-old woman presented with a history of
      multiple episodes of left upper-extremity numbness, mild dysarthria, and agraphia
      occurring over the previous 24 hours. Cranial magnetic resonance imaging revealed
      a scattered watershed infarction of the right hemisphere and a critical stenosis
      of the right ICA. An 81-year-old man awoke with hemiplegia and inability to
      follow commands after undergoing a complicated carotid endarterectomy. Computed
      tomographic perfusion imaging demonstrated an increased time to peak in the left
      middle cerebral territory, and emergent angiography demonstrated both intimal
      flaps and thrombus in the endarterectomy bed. The lesions in both patients were
      treated with endovascular stent placement using both proximal and distal flow
      occlusion--a functional "internal cross-clamping"--for embolic protection. To our
      knowledge, this is the first report of internal trapping and stent placement for
      symptomatic carotid stenosis containing intraluminal thrombus. This treatment
      strategy should be added to the armamentarium of endovascular surgeons in
      selected patients with symptomatic carotid intraluminal thrombus.

PMID- 18077963
TI  - Paroxysmal otalgia due to compression of the intermediate nerve: a distinct
      syndrome of neurovascular conflict confirmed by neuroimaging. Case report.
AB  - The authors present the case of a 52-year-old female patient with a 6-year
      history of intractable paroxysmal otalgia. Preoperative magnetic resonance (MR)
      angiography demonstrated an anterior inferior cerebellar artery loop compressing
      the intermediate nerve in the seventh/eighth cranial nerve complex inside the
      internal auditory canal. The pain resolved completely after a microvascular
      decompression via a retromastoid craniotomy. To the best of the authors'
      knowledge, the combined neuroimaging and intraoperative findings of this case
      provide a unique demonstration that vascular compression of the intermediate
      nerve can be the exclusive cause of paroxysmal otalgia. Magnetic resonance
      imaging and MR angiography can establish the causative mechanism and distinguish
      this otalgia due to vascular compression of the intermediate nerve from other
      pain syndromes that are designated as geniculate neuralgia (GN). The present case
      indicates that intermediate nerve neuralgia is a distinct syndrome of
      neurovascular conflict and a variant of GN. The causative classification of GN
      should be reexamined with the use of advanced MR imaging.

PMID- 18077964
TI  - Neurovascular compression of the abducent nerve causing abducent palsy treated by
      microvascular decompression. Case report.
AB  - Isolated abducent palsy is a symptom that can be caused by many different
      intracranial pathological conditions. In this report the authors describe the
      case of a patient who suffered isolated abducent palsy resulting from vascular
      compression of the sixth cranial nerve; surgical treatment consisted of
      microvascular decompression (MVD). This 56-year-old man presented with short
      lasting episodes of a pulling sensation at the lateral side of his right eye
      associated with intermittent diplopia, followed by a progressive palsy of the
      abducent nerve and constant diplopia. Magnetic resonance imaging revealed a
      neurovascular contact of a dolichoectatic basilar artery with the abducent nerve.
      The patient underwent surgery consisting of a combined supra- and infratentorial
      presigmoid approach and subsequent MVD of the abducent nerve. Postoperatively,
      the abducent nerve palsy resolved within days, and the patient remains free of
      symptoms with a follow-up time of 4 years. This is the first report of a
      neurovascular compression of the abducent nerve treated successfully by MVD.

PMID- 18077965
TI  - Preservation of the lesser occipital nerve during microvascular decompression for
      hemifacial spasm. Technical note.
AB  - The authors report on their technique for preserving the lesser occipital nerve
      (LON) during lateral suboccipital craniotomy. In their technique, the LON, which
      runs along the surface of or just beneath the sternocleidomastoid muscle, is
      identified and preserved. Lesser occipital nerve preservation using their
      technique was attempted in 25 patients who underwent microvascular decompression
      for hemifacial spasm. The LON was successfully preserved in 16 of these patients,
      was impossible to preserve in two patients, and could not be identified in seven
      patients. Among the patients in whom LON preservation was successful, 87.5% were
      free of sensory disturbance 6 months after surgery, whereas both patients in whom
      the LON could not be preserved complained of sensory disturbances in the
      occipital area and the posterior part of the auricula. Fifty-seven percent of the
      patients whose LON could not be identified complained of sensory disturbance.
      Thus, this technique for preserving the LON reduces the incidence of sensory
      disturbance in the occipital region after suboccipital craniotomy for
      microvascular decompression for hemifacial spasm.

PMID- 18077966
TI  - Optimizing computed tomography to reduce artifacts from titanium aneurysm clips:
      an in vitro study. Technical note.
AB  - OBJECT: At many institutions digital subtraction angiography remains the standard
      imaging procedure for the postoperative evaluation of patients following
      placement of a cerebral aneurysm clip largely because of the artifacts produced
      by the clip on computed tomography (CT). The authors evaluated the effect of
      various imaging parameters on the quality of 3D reconstructions from CT scans
      while imaging a phantom to optimize the CT angiograms. METHODS: Using
      multidetector CT scanners with submillimeter detector collimation (0.625 mm), the
      authors scanned a silicone phantom with attached commercial aneurysm clips. Slice
      thickness, reconstruction overlap, kilovolt level, milliampere level, and pitch
      were varied. Neuroradiologists, who were blinded to the scanning parameters,
      rated the reconstructions for image quality and artifact reduction. RESULTS:
      Images of the titanium clip using 140 kV and 380 mA with 0.625-mm overlapping
      reconstructed slices provided excellent 3D visualization of both the clip and the
      aneurysm model, even when using two adjacent clips. CONCLUSIONS: Overlapping
      reconstructions combined with thin-section acquisition can provide detailed
      images of titanium clips and surrounding tissues without the use of low-pitch
      values.

PMID- 18077967
TI  - New transparent peel-away sheath with neuroendoscopic orientation markers.
      Technical note.
AB  - The peel-away sheath in neuroendoscopic surgery offers numerous advantages and
      has many potential applications. However, currently available nontransparent
      sheaths have a critical disadvantage in that disorientation can occur, given the
      limited visible operative field. To overcome this obstacle, the authors have
      developed and clinically applied a new transparent sheath with "navigational
      orientation markers." The clear peel-away sheath provides a transparenchymal
      route, parenchymal protection, and, most importantly, direct visualization of the
      surroundings along the whole trajectory and at the distal edge. The navigational
      orientation markers add further benefits in terms of facilitating orientation in
      the endoscope trajectory, making this tool extremely useful in neuroendoscopic
      surgery.

PMID- 18077968
TI  - Intracranial hypertension due to straight sinus occlusion. Case illustration.

PMID- 18077969
TI  - Appearance of the neuroform stent on computed tomography angiographic images:
      imaging pitfall. Case illustration.

PMID- 18077970
TI  - Neurological manifestations of the acquired immunodeficiency syndrome (AIDS):
      experience at UCSF and review of the literature. 1985.

PMID- 18077971
TI  - Decompression craniotomy.

PMID- 18077972
TI  - Intradural chordoma.

PMID- 18077973
TI  - Evaluation of fine needle aspiration vs. fine needle capillary sampling on
      specimen quality and diagnostic accuracy in endoscopic ultrasound-guided biopsy.
AB  - OBJECTIVE: To compare percutaneous and endoscopic ultrasound (EUS)-guided biopsy
      techniques. STUDY DESIGN: From July 2005 to February 2006, all patients referred
      for EUS-guided fine needle aspiration (FNA) were considered. If inclusion
      criteria were met, the first 2 biopsy passes were performed without suction (fine
      needle capillary [FNC] sampling). Two additional passes were performed using the
      same needle with 10 mL of applied suction (FNA). A single blinded pathologist
      later retrospectively evaluated each set of slides. Fifty-three patients met
      inclusion criteria. The study group comprised pancreatic masses (23), lymph nodes
      (26), subepithelial masses (3) and liver lesion (1). There were 38 malignant and
      15 benign lesions. RESULTS: No statistically significant differences were found
      with the scoring systems considered in the study. In the subgroups of patients
      with pancreatic masses, lymph nodes, benign disease and malignant disease, no
      statistically significant outcomes were noted. CONCLUSIONS: No difference exists
      between quality and diagnostic accuracy of specimens obtained from EUS-guided
      tissue acquisition via FNC and FNA. The decision to use FNC or FNA should be left
      to the discretion of the individual endosonographer.

PMID- 18077974
TI  - Cytodiagnosis of filarial infections from an endemic area.
AB  - OBJECTIVE: To throw light on cytologic findings as a possible mode of diagnosis
      of lymphatic filariasis. STUDY DESIGN: Filariasis has worldwide distribution, but
      lymphatic filariasis predominantly affects tropical and subtropical regions.
      Demonstration of microfilaremia, the specific test for diagnosis of lymphatic
      filariasis, often shows false negative results in endemic areas. The present
      study, done in an endemic area, showed the presence of microfilariae or adult
      worms of Wuchereria bancrofti in fine needle aspirates collected from
      amicrofilariaemic cases. In a few cases the discovery was incidental. A total
      4,534 cases undergoing cytologic evaluation were carefully screened for the
      presence of adult worms or larvae, irrespective of clinical diagnosis.
      Microfilariae were demonstrated in both clinically suspected cases of filariasis
      and asymptomatic cases. RESULTS: A total of 1 positive cases were found; in 4
      cases the clinical diagnosis was lymphatic filariasis, and 7 cases were
      asymptomatic. All 11 cases were amicrofilariaemic. CONCLUSION: Various
      sophisticated investigations are used for diagnosis of lymphatic filariasis
      without microfilaremia. Fine needle aspiration cytology, being a cheap, simple
      and easy procedure, may have some role in this field, but further detailed
      studies are needed before any final claim.

PMID- 18077975
TI  - Value of repeated fine needle aspiration cytology in patients with nodular
      goiter.
AB  - OBJECTIVE: To assess the value of reaspiration cytology in benign nodular thyroid
      disease. DESIGN: We prospectively studied 400 patients (365 women, 35 men) aged
      46 years (18-89) with nodular thyroid disease and initial benign fine needle
      aspiration cytology (FNAC). Reaspiration of the same nodule was performed in a
      median follow-up time of 14 months (6-18). RESULTS: Repeat FNAC was benign in 346
      patients (86.5%), insufficient for diagnosis in 42 (10.5%), suspicious in 16
      (2.5%) and malignant in 2 (0.5%). All diagnostic changes to suspicious malignant
      cytology took place in patients with solitary nodules. Surgery confirmed thyroid
      cancer in the 2 patients with malignant cytology, in 5 of 10 patients with
      suspicious cytology and in none of 39 patients with benign cytology who underwent
      surgery for other reasons. Clinical changes (size increase or local symptoms)
      were not related to changes in cytologic diagnosis after a second aspiration, nor
      with the results of the biopsy. CONCLUSION: Repeat aspiration cytology of thyroid
      nodules may correct initial false negative results because of cytologic
      misdiagnosis, occurring in 1.75% of patients, whereas clinical changes did not
      contribute to diagnosis change. Repeat aspiration cytology is recommended in all
      patients with nodular goiter.

PMID- 18077976
TI  - Cutaneous manifestations in non-Hodgkin's lymphoma.
AB  - OBJECTIVE: To examine and subtype cutaneous lymphoma specimens for diagnosis.
      STUDY DESIGN: Aspiration smears from skin lesions and lymph nodes diagnosed as
      non-Hodgkin's lymphoma (NHL) on cytology in 6 cases over a period of 1 year were
      reviewed. Two were follow-up cases of nodal lymphoma and were receiving
      chemotherapy, during which they developed skin lesions. In 4, the patients had
      cutaneous lesions as a presenting manifestation. Cytologic findings were
      correlated with histologic and hematologic findings and immunocytochemical
      markers for subtyping. RESULTS: Patients ranged from 14 to 50 years, with equal
      sex ratio. All presented with 0.5-5 cm multiple nodular, ulcerated and fungating
      skin lesions at various body sites. The aspirate was satisfactory in all cases.
      Cytologically, all cases were diagnosed as NHL. They were then
      immunocytochemistry subtyped as various lymphomas. CONCLUSION: Cutaneous lymphoma
      should always be considered in the presence of predominantly atypical lymphoid
      cells in smears from nodular and fungating skin lesions, even in the absence of a
      definitive clinical diagnosis.

PMID- 18077977
TI  - Evaluation of abdominal fat pad aspiration cytology and grading for detection in
      systemic amyloidosis.
AB  - OBJECTIVE: To evaluate the diagnostic efficacy of abdominal fat pad aspiration
      cytology as a screening procedure for systemic amyloidosis and to assess the
      clinical usefulness of semiquantitative grading criteria of fat pad amyloid
      deposits. STUDY DESIGN: Aspiration cytology samples from 297 cases of abdominal
      fat pad were retrospectively analyzed for amyloid deposits. The smears were
      graded semiquantitatively. The deposits in the smears were compared with
      histologic evidence of amyloidosis in deeper tissues in 44 cases. RESULTS:
      Retrospective analysis of 297 cases of aspiration cytology revealed amyloid in 90
      cases. Follow-up biopsies from deeper tissues in 44 cases showed presence of
      systemic amyloidosis in 13 cases. The sensitivity and specificity of abdominal
      fat pad fine needle aspiration cytology was 78% and 93%, respectively. The
      positive predictive value was 84% and negative predictive value 90%. CONCLUSION:
      Fat pad aspiration cytology is a useful screening procedure for diagnosis of
      systemic amyloidosis. Patients with grade 1 deposits should not undergo a toxic
      therapeutic regimen on the basis of fat pad cytology alone; histologic
      confirmation of visceral amyloid deposition in deeper tissue is advised. Patients
      with grades 2 and 3 deposits may undergo suitable therapy for amyloidosis.

PMID- 18077978
TI  - Evaluation of the FocalPoint GS system performance in an Italian population-based
      screening of cervical abnormalities.
AB  - OBJECTIVE: To evaluate the FocalPoint Location-Guided Screening (FPGS)
      performance in computer-assisted primary screening of Papanicolaou-stained
      cervicovaginal smears. STUDY DESIGN: A total of 37,306 routine consecutive
      conventional Pap slides were prospectively processed on the FPGS. Each slid
      designated by the instrument as Review was reported according to results obtained
      using a GS Review Station. Subsequently, all slides under went conventional
      manual rapid screening and reported results were compared. RESULTS: Of the slides
      initially submitted to the FPGS, 34,004 (91.15%) were qualified for scanning.
      Within these slides, the system classified 7,399 (21.8%) as needing No Further
      Review and ranked to Review the remaining 26,605 (78.2%). Of the 418 cellular
      abnormalities found, 409 were classified for Review by FPGS and 9 minor grade
      lesions were classified in the "No Further Review" population. Overall, 352 (86%)
      of atypical squamous cell (ASC)+ were ranked in high-score quintiles, including
      96 (94%) of the 102 high-grade squamous intraepithelial lesion (HSIL) or worse.
      Location-guided software identified cellular abnormalities, in the automatically
      selected fields of view, in 378 (92%) of the ranked abnormal slides, showing a
      sensitivity > 95% on SILs. CONCLUSION: Slide ranking and location-guided
      screening features are of value in detecting and triaging abnormal smears.

PMID- 18077979
TI  - Interlaboratory quality control in gynecologic cytopathology using the novel
      CONQUISTADOR software. Interobserver reproducibility in the Latin American
      screening study.
AB  - OBJECTIVE: The recently developed software (CONQUISTADOR), capable of computing
      all intralaboratory and interlaboratory quality control (QC) indicators, was used
      to evaluate the diagnostic agreement among 4 cytology laboratories participating
      in the LAMS Study. STUDY DESIGN: The study was an interlaboratory exchange of
      specially designed 5 slide sets, each comprising 20 (conventional cytology)
      slides. At the first step, 80 slides (with "clear-cut" cases) were divided into
      four sets (A, B, C, D) of 20 specimens, each including inadequate and negative
      cases as well as in different proportions of all diagnostic TBS 2001 categories.
      In the second round, a fifth set (E) of 20 slides ("difficult cases") was
      designed, with all diagnostic categories, ASC and AGC included. Common measures
      of reproducibility (kappa and weighted kappa), accuracy (SE, SP, PPV, NPV) and 3
      indices of diagnostic variability were calculated for sets A-D and set E,
      separately. RESULTS: For the 5 slide sets together, the weighted kappa was 0.8
      (95% CI 0.76-0.85), which is the lower limit of the "almost perfect" ranking of
      kappa statistics, indicating an excellent interlaboratory agreement. The
      interlaboratory reproducibility was lower only for the difficult set (E).
      Similarly, the sensitivity for set E (70.0%) was lower than that (92.1%) for sets
      A-D. The diagnostic variability indices were not substantially different between
      the difficult (set E) and clearcut (sets A-D) cases. CONCLUSION: High
      interlaboratory reproducibility was obtained for sets A-D ("clear-cut" cases),
      while more interlaboratory variation was evident in the difficult samples. The
      new CONQUISTADOR software is a valuable tool in calculating the indicators needed
      in this intralaboratory and interlaboratory.

PMID- 18077980
TI  - Microscopic diagnosis of vulvovaginal candidiasis in stained vaginal smears by
      Dutch general practitioners.
AB  - OBJECTIVE: To determine the accuracy of the microscopic diagnosis of vulvovaginal
      candidiasis (presence of [pseudo] hyphae and blastospores) in stained vaginal
      smears in clinical practice. STUDY DESIGN: General practitioners trained in
      diagnosing vulvovaginal candidiasis performed microscopy of 324 stained vaginal
      smears. These smears were sent to the pathologist for confirmation of the
      microscopic diagnosis of the clinician; cytologic diagnosis by the pathologist
      was considered the gold standard. RESULTS: In 104 of the 342 cases Candida was
      established by the pathologist. The clinicians made 24 false positive and 50
      false negative diagnoses of Candida. Sensitivity and specificity of the
      microscopic diagnoses of the clinicians were 52% and 89%, respectively. The most
      frequent reason for a false positive diagnosis was presence of hairs, whereas the
      most frequent reason for a false negative diagnosis was understaining of the
      smear. CONCLUSION: This study shows that even in stained smears it is difficult
      for clinicians to recognize blastospores and (pseudo)hyphae. Efforts are clearly
      needed to improve the quality of the clinical diagnosis of vulvovaginal
      candidiasis.

PMID- 18077981
TI  - Comparison of NCL-hTERT antibody reactivity and telomere repeat amplification
      protocol in situ in effusions.
AB  - OBJECTIVE: To compare the performances of 2 methods, telomerase repeat
      amplification protocol (TRAP) in situ and antibodies to the hTERT protein, in
      assessing telomerase activity. STUDY DESIGN: TRAP in situ and
      immunohistochemistry with a commercial antibody (NCL-hTERT) was performed on 54
      body cavity effusions. The results were compared and correlated to diagnosis.
      RESULTS: Thirty-four effusions from patients with verified malignant disease
      contained cytologically malignant cells. Both methods were positive in 33 of the
      cases, whereas only hTERT was positive in 1 case. Twenty effusions, all
      containing mesothelial cells, came from patients with benign conditions. In 2
      fluids atypical, hyperplastic mesothelial cells were both TRAP in situ and hTERT
      positive. All remaining 18 fluids were TRAP in situ negative, whereas 12 of 18
      were hTERT positive. Thus the results of TRAP in situ and hTERT
      immunohistochemistry disagreed in 1 of 34 (3%) malignant and 12 of 20 (60%)
      benign cases. CONCLUSION: The sensitivities for malignancy were similar for TRAP
      in situ and hTERT immunohistochemistry. The specificity of the applied hTERT
      antibody was significantly lower, due to hTERT reactivity in mesothelial cells.

PMID- 18077982
TI  - Increased sensitivity of anal cytology in evaluation of internal compared with
      external lesions.
AB  - OBJECTIVE: To investigate the impact of keratin on the accuracy of internal and
      external anal brush sampling of known lesions. STUDY DESIGN: A group of 46 human
      immunodeficiency virus (HIV)-seropositive patients underwent external and
      internal anal brush sampling before biopsy of known lesions. RESULTS; A total of
      92 ThinPrep (46 external, 46 internal) an 211 biopsies were examined. The
      sensitivity and specificity for internal lesions positive and negative for anal
      squa mous intraepithelial lesion (ASIL) was 91.1% and 42.8%, respectively; and
      for external lesions was 79.4% and 100%, respectively. Low cellularity on
      cytology and markedly thickened keratin on biopsy were significantly more common
      in external compared with internal lesions (p < 0.0001). CONCLUSION: We conclude
      that hyperkeratosis interferes with adequate sampling and accurate grading of
      external anal lesions by brush sampling.

PMID- 18077983
TI  - Qualitative and quantitative analysis of cytologic assessment of astrocytoma,
      oligodendroglioma and oligoastrocytoma.
AB  - OBJECTIVE: To evaluate the usefulness of intraoperative cytology for differential
      diagnoses of astrocytoma, oligodendroglioma and oligoastrocytoma. STUDY DESIGN:
      Qualitative analysis of cytologic features of the 3 brain tumors was conducted
      using intraoperative touch or squash preparations that were stained with the
      Papanicolaou method, targeting the cellular density, cytoplasmic and nuclear
      profiles and blood vessel morphology. In addition, we attempted a computer
      assisted image analysis of tumor cell nuclei and compared the results with
      qualitative observations. RESULTS: Astrocytomas were characterized by many
      fibrillary cytoplasmic processes and large, irregular nuclei. Oligodendrogliomas
      were characterized by small, round nuclei and a fine, delicate capillary network.
      In both tumors of a higher grade, anaplastic large nuclei and proliferating
      endothelial cells were noted. Oligoastrocytomas showed combined cytologic
      profiles of astrocytomas and oligodendrogliomas. Quantitative studies suggested
      that nuclei of oligodendroglial tumors were significantly rounder than those of
      astrocytomas. In general, the quantitative results were consistent with the
      qualitative observations. CONCLUSION; Cytologic evaluation using touch or squash
      preparations is of great help for intraoperative differential diagnosis of
      astrocytoma, oligodendroglioma and oligoastrocytoma. Cytologic as well as
      histologic assessment should be conducted at the intraoperative diagnosis of
      these tumors.

PMID- 18077984
TI  - Oncocytic carcinoid tumor of the lung: a case report of diagnostic pitfall in
      filter membrane preparation of bronchial washings.
AB  - BACKGROUND: Oncocytic carcinoid tumor of the lung is a rare variant of pulmonary
      carcinoid. This report describes the morphologic appearance of this rare tumor on
      filter membrane preparation along with potential pitfalls. CASE: A 49-year-old
      woman presented with cough and expectoration. On chest radiograph a mass lesion
      was seen in the upper zone of the right lung. Bronchial washings were sent for
      evaluation. On filter membrane (Millipore) preparation of bronchial washing the
      possibility of a non-small cell carcinoma, possibly squamous, was suggested.
      Right upper lobectomy was subsequently performed and a histologic diagnosis of
      oncocytic carcinoid given. The cytomorphologic features of this tumor on the
      Millipore preparation were reviewed. CONCLUSION: Differential diagnosis of
      oncocytic carcinoid should be kept in mind while assessing cytologic material
      when tumor cells show abundant granular cytoplasm and prominent nucleoli.
      Oncocytic carcinoid also must be differentiated from oncocytoma and granular cell
      tumor. Immunocytochemistry and electron microscopy are useful in confirming the
      diagnosis.

PMID- 18077985
TI  - Fine needle aspiration of follicular variant of papillary thyroid carcinoma
      presenting with pleural effusion: a case report.
AB  - BACKGROUND: Malignant pleural effusion in association with mesothelioma,
      bronchogenic carcinoma and breast carcinoma is common, although less frequently
      reported with other malignancies. We report a follicular variant of papillary
      thyroid carcinoma (FVPTC), diagnosed on fine needle aspiration cytology (FNAC) of
      thyroid and lymph nodes and subsequently proved to have metastasized to the
      pleural cavity. CASE: A 46-year-old man presented with history of breathlessness,
      thyroid swelling, pleural effusion and bilateral cervical lymphadenopathy. FNAC
      of the thyroid swelling and the lymph nodes showed features of FVPTC with
      cervical lymph node metastasis. Pleural fluid examination led to suspicion of
      pleural involvement by metastatic deposit, confirmed by subsequent pleural
      biopsy. CONCLUSION: Thyroid malignancies presenting with pleural effusion are
      rare. In this case, although pleural fluid cytology suggested involvement of
      pleura, a definitive diagnosis could be rendered only on pleural biopsy. An
      ancillary aid, such as immunocytochemistry, could have helped establish pleural
      involvement on routine pleural fluid cytology alone. This case emphasizes the
      possible existence of rare cases of FVPTC that may be associated with a dismal
      prognosis. In our case, initial diagnosis of FVPTC could be made only on
      correlating FNA features of thyroid aspirate with those of lymph node aspirate.

PMID- 18077986
TI  - Basement membrane-like substance in cytologic diagnosis in clear cell
      adenocarcinoma of the minor salivary gland of the palate. A case report.
AB  - BACKGROUND: Clear cell adenocarcinoma (CCA) of the minor salivary gland accounts
      for < 1% of all tumors of the salivary gland. CASE: A 32-year-old woman with a
      history of papillary carcinoma of the thyroid 1 year earlier complained of pain
      on the left side of the neck. After a detailed examination, the patient underwent
      the resection of a tumor located at the palate. Imprint cytology of the tumor
      revealed cohesive tumor cells of uniform size containing an abundant clear
      cytoplasm and round nuclei with extra but fine granular chromatin and conspicuous
      nucleoli. A basement membrane-like substance (BMS) was stained in light green
      with Papanicolaou staining and was positive for laminin with immunohistochemical
      staining. Histopathologic analysis confirmed the trabecular or nest-like
      arrangement of the cells with the clear cytoplasm and BMS substance surrounded by
      tumor cells, which were positive for laminin and AE1 immunohistochemically.
      CONCLUSION: Although CCA of the palate is extremely rare, an accurate cytologic
      diagnosis can be made if the characteristic findings of CCA, including BMS, are
      imaged.

PMID- 18077987
TI  - Histologic findings and comparison with sputum smears in pulmonary aspiration of
      vegetable particles in syringomyelia: a case report.
AB  - BACKGROUND: Pulmonary aspiration of vegetable matter may be a serious cause of
      lung damage, requiring, almost always, the help of a histopathologic examination.
      CASE: We report the case of a 55-year-old woman with a granulomatous pneumonitis
      due to repeated pulmonary aspiration of vegetable particles and affected by a
      syringomyelia. Histologic findings from a lobectomy section are shown and
      compared with those observed in different cytologic sputum samples. CONCLUSION:
      The recognition of uncommon morphologic structures, and their comparison with
      others already known, both in histologic sections and in cellular smears, may be
      useful when it comes to establishing a sure diagnosis.

PMID- 18077988
TI  - Fine needle aspiration biopsy for preoperative workup of pancreatic cystic
      neoplasms: report of 4 cases.
AB  - BACKGROUND: Cystic neoplasms of the pancreas comprise a pathologically
      heterogeneous group of lesions that usually present with similar, nonspecific
      clinical features. Based on the diagnosis, treatment varies from watchful
      observation of the lesion to total surgical resection of the pancreas. Therefore
      the importance of a precise and accurate diagnosis on fine needle aspiration
      (FNA) biopsy cannot be overemphasized from the patient management standpoint.
      There is debate regarding the accuracy of FNA diagnosis of cystic lesions of the
      pancreas. We report 4 cases and review the literature to explore and highlight
      the cytologic findings and diagnostic pitfalls that may help the cytopathologist
      accurately distinguish mucinous cystic neoplasm (MCN), intraductal papillary
      mucinous neoplasm (IPMN), serous cystadenoma (SCA) and ductal adenocarcinoma
      (DAC). CASES: We present 4 cases of patients with abdominal masses who underwent
      either computed tomography (CT)-guided or endoscopic ultrasound (EUS)-guided FNA
      biopsy as preoperative workup. Based on the cytologic diagnosis, the patients
      underwent surgery. CONCLUSION: Our cases illustrate the cytologic criteria that
      help the cytopathologist distinguish among MCN, IPMN, SCA and DAC. Correlation
      with clinical and radiologic findings is strongly advocated for accurate
      diagnosis. We describe the diagnostic pitfalls frequently encountered in these
      cases and how to avoid them.

PMID- 18077989
TI  - Fine needle aspiration cytology diagnosis of metastatic sarcomatoid prostatic
      carcinoma.

PMID- 18077990
TI  - Fine needle aspiration cytology of a metastatic skin nodule diagnosed as a
      dedifferentiated chondrosarcoma.

PMID- 18077991
TI  - Scanning electron microscopy in ultrastructural morphology of perilesional
      keratinocytes in pemphigus foliaceous.

PMID- 18077992
TI  - Rising PSA in nonmetastatic prostate cancer.
AB  - Rising prostate-specific antigen (PSA) in nonmetastatic prostate cancer occurs in
      two main clinical settings: (1) rising PSA to signal failed initial local therapy
      and (2) rising PSA in the setting of early hormone-refractory prostate cancer
      prior to documented clinical metastases. Most urologists and radiation
      oncologists are very familiar with the initial very common clinical scenario,
      commonly called "biochemical recurrence." In fact, up to 70,000 men each year
      will have a PSA-only recurrence after failed definitive therapy. The ideal
      salvage therapy for these men is not clear and includes salvage local therapies
      and systemic approaches, of which the mainstay is hormonal therapy. Treatment
      needs to be individualized based upon the patient's risk of progression and the
      likelihood of success and the risks involved with the therapy. It is unknown how
      many men per year progress with rising PSA while on hormonal therapy without
      documented metastases. This rising PSA disease state is sometimes called, "PSA
      only hormone-refractory prostate cancer." As in the setting of initial
      biochemical recurrence, evidence-based treatment options are limited, and taking
      a risk-stratified approach is justified. In this article, we will explore these
      prostate cancer disease states with an emphasis on practical, clinically
      applicable approaches.

PMID- 18077993
TI  - Dermatologic challenges in cancer patients and survivors.
AB  - The increased approval of anticancer agents has led to unprecedented results,
      with improved quality of life and longer survival times, resulting in millions of
      individuals living with a diagnosis of cancer. Whereas these novel medical,
      surgical, and radiation regimens, or combinations thereof, are largely
      responsible for these remarkable achievements, a new, unexpected constellation of
      side effects has emerged. Most notably, cutaneous toxicities have gained
      considerable attention, due to their high frequency and visibility, the relative
      effectiveness of anti-skin toxicity interventions, and the otherwise decreasing
      incidence of systemic or hematopoietic adverse events. Optimal care dictates that
      dermatologic toxicities must be addressed in a timely and effective fashion, in
      order to minimize associated physical and psychosocial discomfort, and to ensure
      consistent antineoplastic therapy. Notwithstanding the critical importance of
      treatment-related toxicities, dermatologic conditions may also precede, coincide,
      or follow the diagnosis of cancer. This review provides a basis for the
      understanding of dermatologic events in the oncology setting, in order to promote
      attentive care to cutaneous health in cancer patients and survivors.

PMID- 18077994
TI  - Liposomal doxorubicin in combination with bortezomib for relapsed or refractory
      multiple myeloma.
AB  - PURPOSE: On May 17, 2007, doxorubicin HCl liposome injection (Doxil) in
      combination with bortezomib (Velcade) received approval from the US Food and Drug
      Administration (FDA) for the treatment of relapsed or refractory multiple myeloma
      after at least one prior therapy that has not included bortezomib. Liposomal
      doxorubicin's efficacy and safety were demonstrated in a phase III, randomized,
      multicenter, international trial comparing the combination of this agent plus
      bortezomib vs bortezomib alone in multiple myeloma patients who had not
      previously received bortezomib and had received at least one prior therapy. Here
      we summarize the FDA review of the data that support this approval. EXPERIMENTAL
      DESIGN AND RESULTS: An interim analysis of time to disease progression (TTP), the
      primary endpoint, was conducted after 249 TTP events in this study that
      randomized 324 patients to liposomal doxorubicin plus bortezomib treatment and
      322 patients to bortezomib monotherapy. Time to progression was significantly
      prolonged in the combination arm (median TTP = 9.3 months) compared with
      bortezomib monotherapy (median TTP = 6.5 months), P < .0001 (log-rank test);
      hazard ratio = 0.55 (95% confidence interval = 0.43-0.71). The response rates
      were similar between the two arms and not statistically different; however, among
      responding patients, the median duration of response was longer with the
      combination--10.2 months compared to 7.0 months in the monotherapy arm. Adverse
      reactions occurred more frequently with the combination therapy. As compared to
      the monotherapy, frequent grade 3/4 adverse reactions with the combination were
      neutropenia and thrombocytopenia. CONCLUSIONS: Liposomal doxorubicin received FDA
      approval for use in combination with bortezomib in patients with multiple myeloma
      who have not previously received bortezomib and have received at least one prior
      therapy.

PMID- 18077995
TI  - MRI and breast cancer: role in detection, diagnosis, and staging.
AB  - Increasing experience with magnetic resonance imaging (MRI) has raised important
      questions about how it should be used in breast cancer screening, and for
      presurgical evaluation and posttherapy follow-up of women with this disease.
      Overall, the availability of MRI as an adjunct to mammography and ultrasound
      offers clear clinical benefit to women at increased risk of breast cancer
      development due to BRCA1 and BRCA2 mutations, and to women presenting with
      axillary adenopathy and an occult primary breast tumor. In contrast, its benefit
      for routine selection of breast conservation or further assessment of lobular
      carcinoma in women of average risk has not been demonstrated. This article
      reviews the use of MRI in these settings, with an emphasis on the clinical
      outcomes that have been observed to date.

PMID- 18077996
TI  - Reducing the burden of cancer.

PMID- 18077997
TI  - Einheit und Vielheit--unity and plurality.

PMID- 18077998
TI  - [In memoria. Rolf Bertolini].

PMID- 18077999
TI  - Three-dimensional reconstruction of medieval child mummy in Yangju, Korea, using
      multi-detector computed tomography.
AB  - Recently reported studies on the medieval mummies in Korea have been regarded as
      an invaluable source for studying the physical characteristics of medieval
      Koreans. However, since the reported medieval mummies were re-buried by their
      descendants without any scientific investigations, the development of a brief,
      non-invasive investigation technique was desperately needed among the researchers
      in Korea. In this regard, we tried to apply high-quality multi-detector computed
      tomography (MDCT) with three-dimensional (3D) reconstructions and multi-planar
      reformat (MPR) to investigate Korean mummies. In our study, after 1.25 or 2.5mm
      thin slice axial images were taken, 3D reconstruction and MPR were performed to
      get more accurate information about internal organs. In this trial, we
      successfully showed high-quality images for the brain, muscles, bones, heart and
      liver. During various trials for getting selected organs, we could make the 3D
      reconstructed images of them. Since we could show that the current MDCT technique
      could be useful for obtaining high-quality 3D reconstructed images of the
      internal organs of Korean mummies, this technique will be used in forthcoming
      similar cases, which could not be investigated using invasive techniques.

PMID- 18078000
TI  - Morphometric study of the brachiobicarotid trunk in human fetuses.
AB  - The study was conducted to define a normal range for the length, external
      diameter and volume of the brachiobicarotid trunk during gestation. The material
      examined consisted of 128 human fetuses of both sexes (63 male, 65 female) aged
      from 15 to 34 weeks, from spontaneous abortions or stillbirths. The arterial bed
      was filled with white Latex LBS 3060, specimens were fixed in a 10% formalin, and
      then branches of the aortic arch were dissected, recorded using a camera, and
      digitalized to JPEG images. Afterwards, the brachiobicarotid trunks underwent
      morphometric analysis with the digital image analysis system of Leica QWin Pro16.
      Regression analysis was used to investigate the growth of the brachiobicarotid
      trunk during gestation. The brachiobicarotid trunk was observed in 27 of the 128
      fetuses studied (21.09%). The results showed the brachiobicarotid trunk length as
      a function of fetal age, which could be expressed by y = -1.250+0.1433x+/-
      0.7682, and the brachiobicarotid trunk diameter by y = -3.034+0.2845+/-0.4253.
      The volumetric growth of the brachiobicarotid trunk followed the quadratic
      function y = 178.5-19.69x+0.545x2+/-20.112. The correlation coefficients between
      arterial length or external diameter and fetal age, and the coefficient of
      determination between arterial volume and fetal age were as follows: r = 0.76 for
      length, r = 0.97 for external diameter, and R2 = 0.84 for volume (P<0.001). The
      relative diameter of the brachiobicarotid trunk increased from 0.738+/-0.089 to
      0.916+/-0.088 during the study period.

PMID- 18078001
TI  - Morphometrical analysis of the human suprarenal gland between the 4th and 7th
      months of gestation.
AB  - The present study's purpose has been to examine the development of the human
      suprarenal glands (SGs) during the prenatal period. Special attention was paid to
      sexual dimorphism and the differences between the parameters of the right and
      left SGs. Specimens were obtained from 187 human fetuses spontaneously aborted
      between the 4th and 7th months of gestation. The SGs were dissected from the
      fetuses after an immersion and preservation period of 3-24 months in 9% formalin
      solution. The mass and linear dimensions of each isolated SG were obtained, and
      these data revealed a progressive two-fold increase between the 4th and 7th
      months of gestation. There was a gradual reduction in the ratio of the SG mass to
      the overall mass of the fetus with a marked decrease evident between the 4th and
      5th months. Statistical analysis of both SGs showed significant differences
      between sexes in the mass and in the thickness of the left SG during the 5th and
      6th months of gestation. Differences in the mass and linear dimensions of the
      left and right SGs were recorded from the 5th month of gestation to the 7th
      month. The mass and volume of the left SGs were higher than those on the right
      side. This allometric analysis provides data from a large sample of human fetuses
      and will later aid in microscopic and ultrasonographic studies.

PMID- 18078002
TI  - Keratinization of sheath and calamus cells in developing and regenerating
      feathers.
AB  - The present ultrastructural and immunocytochemical study on developing and
      regenerating feathers in the chick, zebrafinch and quail describes the formation
      of alpha-keratin cells in the sheath and their transition into beta-keratin cells
      in the calamus. In the first stages of feather formation cells are produced in
      the lower part of the follicle, migrate upward and form the elongating sheath of
      the feather filaments that grows outside the follicle. Sheath cells initially
      (anagen) contain bundles of alpha-keratin filaments. By the end of anagen at the
      base of the feather inside the follicle cells in continuation with the sheath
      produce homogenous bundles with the aspect of beta-keratin filaments. These
      bundles are immunoreactive for beta-keratin antibodies suggesting that beta
      keratin is added to the initial framework of alpha-keratin. The packing of dense
      and hard corneous material in these cells eventually forms the calamus. The
      Latter corneous tissue replaces at the base of feathers the softer sheath present
      in more apical regions of the feather filaments. The increase of feather (beta)
      keratin in cells of the calamus determines the formation of long bundles of
      corneous material. The modality of cornification in feathers is compared to the
      process of hard cornification of reptilian scales and claws and mammalian hairs
      and nails.

PMID- 18078003
TI  - The potential of proteomics for providing new insights into environmental impacts
      on human health.
AB  - The effects of environmental chemicals have traditionally been detected by
      monitoring biomarkers of exposure or biomarkers of effect. Proteomics, the study
      of the complete profile of proteins in a given cell, tissue or biological system,
      is a new approach using a set of high-throughput methodologies with a wide
      dynamic range that makes possible the discovery of novel biomarkers. This article
      reviews the application of two-dimensional electrophoresis and mass-spectrometry
      methods to environmental toxicology. Emphasis is placed on the protein-expression
      signature approach and on identifying redox-based post-translational protein
      modifications. The methodological links between studies in sentinel organisms and
      humans are explored. Significant limitations and challenges are placed on this
      approach by the shortage of genome sequence data necessary for protein
      identification and the growing requirement for more stringent study design.
      Proteomics will continue to be an important toolkit to help address the growing
      environmental threat posed by nanoparticles and endocrine disrupting agents.

PMID- 18078004
TI  - Occupational causes of chronic obstructive pulmonary disease.
AB  - The relation between Chronic Obstructive Pulmonary Disease (COPD, including
      chronic bronchitis and emphysema (CBE), and exposure to coal dust is well
      established. This paper reviews the evidence relating to other occupational
      causes of COPD, including industries associated with exposure to fumes, chemical
      substances, and dusts. A review of key literature has been carried out with a
      focus on the magnitude of risks and levels of exposure causing disabling health
      effects. The literature suggests that elevated risks of developing COPD are
      clearly associated with several occupations, with risk estimates being high in
      some, even after taking into account the effect of confounders, such as smoking.
      Of particular concern are agricultural workers who can be exposed to a variety of
      gases and organic dusts, among whom CBE is clearly elevated, particularly for pig
      farmers and exposure to endotoxins, with an increased annual decline in lung
      function. Similarly, cotton textile workers are exposed to a mixture of
      substances affecting development of atopy, byssinosis, and CBE, and across-shift
      and long-term decline in lung function. Atopy also has an important role in the
      development of COPD in flour mill workers and bakers, with those sensitized to
      bakery allergens having a greater lung function decline than non-sensitized
      individuals. Welding processes involve a range of potential chemical, physical
      and radiation hazards. The average reduction in FEV1 associated with welding
      fumes is similar to that associated with smoking. Challenges in assessing the
      evidence include variation in diagnostic methods; concurrent exposure to
      cigarette smoke (direct or second-hand) and multiple work-place irritants;
      healthy worker selection/survivor effects; poor exposure definition. Raising
      awareness of occupational causes of COPD among employers, employees, and health
      service professionals is important.

PMID- 18078005
TI  - Environmental toxicology and health effects associated with hexachlorobenzene
      exposure.
AB  - The synthetic industrial chemical hexachlorobenzene (HCB) is a white crystalline
      solid compound. The substance is a bioaccumulative, persistent, and toxic
      pollutant. Historically HCB was commonly used as a pesticide and fungicide.
      Although HCB production and use has ceased in many countries, the compound is
      still generated inadvertently, as a byproduct and/or impurity in the manufacture
      of various chlorinated compounds, and released into the environment.
      Hexachlorobenzene is ubiquitous in air, water, soil, and biological matrices, as
      well as in major environmental compartments. Exposure to this substance is a
      public health concern because of its association with a wide range of adverse
      health effects. The International Agency for Research on Cancer and the United
      States Environmental Protection Agency classify HCB as a probable human
      carcinogen. Although globally the consumption of HCB-contaminated food is the
      principal source of environmental exposure, exposure can also occur through the
      inhalation of HCB-contaminated air, by dermal contact, or through in utero
      exposure and breast milk. In addition to cancer, the human health effects
      associated with HCB exposure involve systemic impairment (thyroid, liver, bone,
      skin), as well as damage to the kidneys and blood cells and the immune,
      endocrine, developmental, and nervous systems. In this review, we discuss the
      sources of HCB and the potential for human exposure, as well as systemic,
      carcinogenic, and teratogenic health effects.

PMID- 18078006
TI  - Dust mites: using data from an intervention study to suggest future research
      needs and directions.
AB  - Dermatophagoides farinae (Der f 1; referred as Der f hereafter) and D.
      pteronyssinus (Der p 1; referred as Der p hereafter) are common allergy-causing
      mites found in homes worldwide. Mites are more prevalent in humid climates, but
      are rare or absent in drier climates. Levels of dust mite sensitivity have been
      reported between 48% and 63% for asthmatic children. Dose-response relations
      between levels of dust-mite exposure and sensitivity have been reported; yet,
      relatively high levels of dust mite sensitivity (50%-60%) have been found in
      populations exposed to concentrations below the proposed cut-point sensitization
      concentration of 2 microg dust mite per gram of dust. A meta-analysis of 49
      trials involving 2733 patients found that interventions for dust mite-control did
      not result in any clinical benefit to mite-sensitive asthmatics. We assessed the
      impact of replacing old mattresses with dust-mite resistant mattresses on dust
      mite levels, and to a more limited extent, on health outcomes. Replacement
      mattresses were provided to 44 asthmatic children residing in public housing in
      inner city Boston, Massachusetts. At baseline, we found concentrations to exceed
      the cut point of 2 microg g(-1) in only 9% of beds for Der p and 16% for Der f.
      Only 7% of beds for Der f and 5% for Der p exceeded 10 microg g(-1). Dust-mite
      allergy levels were high in these asthmatic children (54% for Der f and 62% for
      Der p) despite low baseline mattress levels. Our intervention reduced Der p (p =
      0.026) and Der f (p < 0.001) below their low starting levels. Investigations are
      needed that (1) evaluate the reduction of dust-mite levels below the suggested
      cutpoints for sensitization and exacerbation; (2) assess the impact of reduction
      of multiple antigens; (3) assess exposure to dust mites outside of the home; and
      (4) test bundled interventions.

PMID- 18078007
TI  - Anti-hemophilic factor (recombinant), plasma/albumin-free method (octocog-alpha;
      ADVATE) in the management of hemophilia A.
AB  - Removal of blood-based additives from recombinant clotting factor concentrates
      continues to be advocated by the hemophilia community due to the history of
      infectious disease transmission with previous blood-derived clotting factor
      concentrates. In 2003, octocog-alpha, antihemophilic factor (recombinant),
      plasma/albumin-free method (ADVATE) was introduced, providing the first third
      generation recombinant factor VIII (rFVIII) concentrate. Completed clinical
      trials have demonstrated ADVATE to be safe and effective in adult and pediatric
      subjects utilizing both prophylactic and on-demand treatment regimens, and for
      perioperative hemostatic coverage. In the five completed studies involving more
      than 200 previously treated patients (PTPs), a single incidence of low-titer, non
      persistent inhibitor was reported. Active post authorization safety surveillance
      (PASS) is being performed to expand the efficacy and safety profile of ADVATE in
      routine clinical practice. Laboratory studies have documented the storage and
      post-reconstitution stability of ADVATE, conferring the desired versatility for
      home treatment. The evolving real-world experience and ongoing studies will
      provide further insight into ADVATE pharmacokinetics, alternative prophylactic
      dosing regimens, methods for perioperative hemostatic management, and utility in
      immune tolerance induction. Experience with ADVATE, and its place in today's
      treatment paradigm, is the focus of this article.

PMID- 18078009
TI  - Calcium channel blockers, angiotensin receptor blockers, and angiotensin
      converting enzyme inhibitors: effectiveness in combination with diuretics or beta
      blockers for treating hypertension.
AB  - This retrospective database analysis compared the effectiveness of
      dihydropyridine calcium channel blockers (DHPs), angiotensin-converting enzyme
      (ACE) inhibitors, and angiotensin receptor blockers (ARBs) added to diuretics or
      beta-blockers. Adults with hypertension treated with diuretic or beta-blocker
      monotherapy between 1998 and 2001 were identified from a large US electronic
      medical records database of primary care practices. Patients were required to
      have a baseline blood pressure (BP) > or =140/90 mmHg (> or =130/80 mmHg for
      diabetes mellitus) and recorded BP measurements within 6 months before and 1-12
      months following index date. Patients were matched 1:1:1 by propensity score to
      correct for differences in baseline characteristics. 1875 patients met study
      criteria and 660 (220 in each cohort) were matched based on propensity scores.
      Matched cohorts had no significant differences in baseline characteristics. Mean
      changes in systolic/diastolic BP were -17.5/-8.8, -15.7/-6.3, and -13.0/-8.0 mmHg
      with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on
      the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal
      attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE
      inhibitors, and ARBs improved BP when added to patients' beta-blocker or diuretic
      therapy. The greatest benefits were observed with DHPs, followed by ACE
      inhibitors, then ARBs.

PMID- 18078008
TI  - The role of HMG-CoA reductase inhibition in endothelial dysfunction and
      inflammation.
AB  - Statin-induced inhibition ofHMG-CoA reductase reduces cholesterol production and
      prevents the formation of many non-steroidal isoprenoid compounds, such as
      farnesylpyrophosphate and geranylgeranylpyrophosphate, that act as lipid
      attachments for the post-translational modification of various proteins,
      including the G-proteins and transcription factors involved in a number of cell
      processes. However, the blockade of isoprenylation elicited by statin treatment
      also has biological effects on cell function that go beyond the decrease in
      cholesterol synthesis: these are the so-called "pleiotropic" effects that mainly
      relate to vascular function. Endothelial dysfunction is an independent predictor
      of cardiovascular events that correlates with inflammation markers/mediators and
      robust predictors of cardiovascular diseases such as increased high-sensitivity C
      reactive protein levels. The results of in vivo and in vitro studies indicate
      that the statins have beneficial effects unrelated to cholesterol lowering, such
      as improving endothelial function, increasing myocardial perfusion, and enhancing
      the availability of nitric oxide. This review describes the pleiotropic effects
      of statins that may be involved in modulating/preventing endothelial dysfunction
      and inflammatory processes, as well as the cellular and molecular mechanisms
      through which they improve endothelial function.

PMID- 18078011
TI  - Aldosterone antagonism in heart failure.
AB  - Aldosterone, a neurohormone known to affect electrolytes, has recently been
      implicated as playing a major role in the progression of heart failure,
      particularly in patients with systolic dysfunction. Major clinical trials
      designed to analyze clinical outcomes using an aldosterone antagonist have been
      done in two groups with heart failure. The first was the Randomized Aldactone
      Evaluation Study, which was done in symptomatic chronic advanced heart failure
      patients and showed that an aldosterone antagonist, spironolactone, reduced
      mortality significantly compared with placebo. Very few of these patients were on
      standard therapy with beta blockade. Another study, the Eplerenone Post
      myocardial infarction Heart failure Efficacy and SUrvival Study (EPHESUS), done
      in post-myocardial infarction patients with heart failure, demonstrated a
      significant reduction in mortality and hospitalizations for patients randomized
      to the aldosterone antagonist eplerenone. These trial results provide the
      background for aldosterone antagonist therapy in chronic advanced heart failure
      patients as well as post-myocardial infarction heart failure patients with
      reduced ejection.

PMID- 18078010
TI  - Comprehensive cardiovascular risk management--what does it mean in practice?
AB  - The continued movement away from the treatment of individual cardiovascular (CV)
      risk factors to managing overall and lifetime CV risk is likely to have a
      significant impact on slowing the rate of increase in cardiovascular disease
      (CVD). However, the management of CVD is currently far from optimal even in parts
      of the world with well-developed and well-funded healthcare systems. Effective
      implementation of the knowledge, treatment guidelines, diagnostic tools,
      therapeutic interventions, and management programs that exist for CVD continues
      to evade us. A thorough understanding of the multifactorial nature of CVD is
      essential to its effective management. Improvements continue to be made to
      management guidelines, risk assessment tools, treatments, and care programs
      pertaining to CVD. Ultimately, however, preventing the epidemic of CVD will
      require a combination of both medical and public health approaches. In addition
      to improvements in the "high-risk" strategy, which forms the basis of current CVD
      management, an increase in the utilization of population-based management
      strategies needs to be made to attempt to reduce the number of patients falling
      within the "at-risk" stratum for CVD. This review outlines how a comprehensive
      approach to CVD management might be achieved.

PMID- 18078012
TI  - Are pleiotropic effects of statins real?
AB  - The clinical benefits of statins are strongly related to their low density
      lipoprotein-cholesterol (LDL-C) lowering properties. However, because mevalonic
      acid (MVA), the product of 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA)
      reductase reaction, is the precursor not only of cholesterol but also of
      nonsteroidal isoprenoid compounds, the inhibition of HMG-CoA reductase may result
      in pleiotropic effects, independent of their hypocholesterolemic properties. The
      discrimination between the pleiotropic from LDL-C lowering effects may
      potentially be more evident during the early phase of treatment since plasma MVA
      levels drop up to 70% within 1-2 hours while a reduction of LDL-C, detectable
      after 24 hours, became significant after 6-7 days. Therefore, the deprivation of
      circulating MVA-derived isoprenoids in the early phase of treatment could be the
      main mechanism responsible for the atheroprotective effect of statins. This early
      window of protection in the absence of LDL-C lowering suggests that the anti
      inflammatory and the pleiotropic properties of statins may have clinical
      importance. Therefore, acute coronary syndromes could represent a clinical
      condition for addressing the early benefits of statins therapy, ie, within 24 h
      of the event, independent of LDL-C lowering.

PMID- 18078013
TI  - Cholesterol lowering for secondary prevention: what statin dose should we use?
AB  - Over the past decade, 17 large placebo-controlled trials have established that
      statin therapy lowers LDL cholesterol and prevents cardiovascular events and
      death in patients with coronary disease or at high risk for atherosclerotic
      events. Nine trials of higher dose vs. lower dose statins (reporting data from
      29,853 patients with coronary artery disease and 486 patients with other
      indications for statin therapy) have established that higher dose statin therapy
      is more efficacious than lower dose therapy in reducing myocardial
      infarctions/coronary death (by 16%) and stroke (by 18%) in patients with coronary
      disease but only reduces all-cause mortality in patients at high risk for
      coronary death (such as patients immediately after acute coronary syndrome).
      Higher dose statins are associated with statistically significantly increased
      risks of myopathy and elevated transaminases compared to lower dose statins;
      while relative risks for these outcomes are 1.2 and 4.0, the absolute increases
      are small (0.5% and 1%). Secondary analyses of these trials using individual
      patient data and multivariate adjustment will be needed to appropriately examine
      the incremental benefits of different LDL targets, and trials are needed to
      determine whether combinations of low dose statins plus other lipid lowering
      agents may achieve better clinical outcomes than higher dose statin therapy
      alone.

PMID- 18078014
TI  - Ischemic preconditioning: protection against myocardial necrosis and apoptosis.
AB  - The phenomenon of ischemic preconditioning has been recognized as one of the most
      potent mechanisms to protect against myocardial ischemic injury. In experimental
      animals and humans, a brief period of ischemia has been shown to protect the
      heart from more prolonged episodes of ischemia, reducing infarct size,
      attenuating the incidence, and severity of reperfusion-induced arrhythmias, and
      preventing endothelial cell dysfunction. Although the exact mechanism of ischemic
      preconditioning remains obscure, several reports indicate that this phenomenon
      may be a form of receptor-mediated cardiac protection and that the underlying
      intracellular signal transduction pathways involve activation of a number of
      protein kinases, including protein kinase C, and mitochondrial K(ATP) channels.
      Apoptosis, a genetically programmed form of cell death, has been associated with
      cardiomyocyte cell loss in a variety of cardiac pathologies, including cardiac
      failure and those related to ischemia/reperfusion injury. While ischemic
      preconditioning significantly reduces DNA fragmentation and apoptotic myocyte
      death associated with ischemia-reperfusion, the potential mechanisms underlying
      this effect have not been fully clarified. A comprehensive understanding of these
      mechanisms and application to clinical scenarios will provide new directions in
      research and translate this information into new treatment approaches for
      reducing the extent of ischemia/reperfusion injury.

PMID- 18078015
TI  - A critical review of anti-adrenergic therapy in patients with heart failure and
      diabetes mellitus.
AB  - Anti-adrenergic therapy has been widely accepted as an important therapeutic
      intervention in patients with chronic heart failure. However, there has been
      continuing controversy regarding the risks and clinical significance of metabolic
      effects of different anti-adrenergic drugs. This review summarizes what has been
      learned from clinical trial evidence regarding the benefits of anti-adrenergic
      drugs in diabetic patients with chronic heart failure.

PMID- 18078016
TI  - Nebivolol in the treatment of chronic heart failure.
AB  - Nebivolol is a highly selective beta1-adrenergic blocker that also enhances
      nitric oxide bioavailability via the L-arginine-nitric oxide pathway, leading to
      vasodilation and decreased peripheral vascular resistance. It is marketed in
      Europe for the treatment of hypertension and heart failure and is currently being
      reviewed for use in the US by the Food and Drug Administration. Nebivolol appears
      to be well tolerated with an adverse event profile that is at least similar, if
      not better, than that of other beta-adrenergic blockers. Studies suggest that
      long-term therapy with nebivolol improves left ventricular function, exercise
      capacity, and clinical endpoints of death and cardiovascular hospital admissions
      in patients with stable heart failure. To date, it is one of the only beta
      adrenergic blockers that have been exclusively studied in elderly patients.
      Additionally, the unique mechanism of action of nebivolol makes it a promising
      agent for treatment of chronic heart failure in high-risk patient populations,
      such as African Americans. This article will review the pharmacologic and
      pharmacokinetic properties of nebivolol as well as clinical studies assessing its
      efficacy for the treatment of heart failure.

PMID- 18078017
TI  - Clinical use of recombinant human activated factor VII (rFVIIa) in the prevention
      and treatment of bleeding episodes in patients with Glanzmann's thrombasthenia.
AB  - Glanzmann's thrombasthenia (GT) is a congenital qualitative platelet disorders
      due to the deficiency or defect of platelet membrane GPIIb/IIIa (integrin
      alpha(IIb)beta3). The standard treatment for bleeding is platelet transfusion but
      repeated transfusion may result in the development of anti-platelet antibodies
      (to HLA and/or GPlIbIIIa) rendering future platelet transfusion ineffective.
      Alternative effective agent(s) are needed. There are increasing reports
      documenting efficacy of high dose rFVIIa in GT patients with adverse events
      uncommon. The efficacy is supported by evidence that high concentration FVIIa
      binds to activated platelet surface and improves thrombin generation to enhance
      deposition (adhesion) and aggregation of platelets lacking GPIIb/IIIa. While
      there are increasing clinical experiences, evidence-based clinical data are not
      available. There is a need for more clinical studies, particularly clinical
      trials, to further assess the efficacy, safety (particularly thrombotic events)
      and optimal regimen ofrFVIIa in GT patients, either singly or in combination with
      other hemostatic agents such as platelet transfusion. In the absence of this
      data, for treatment of severe bleeding in GT patients with platelet antibodies
      and platelet refractoriness, rFVIIa at dose 90 microg/kg every 2 h for 3 or more
      doses could be considered. This more "optimal regimen" derived from a recent
      International Survey needs confirmation with larger studies. What the optimal
      regimen for surgical coverage is remains unresolved.

PMID- 18078018
TI  - Optimizing combination treatment in the management of type 2 diabetes.
AB  - Obtaining the suggested glycemic control is the most important achievement in
      order to prevent cardiovascular complications in patients with type 2 diabetes.
      Monotherapy often fails after a period of treatment, so that multiple drugs are
      needed to achieve effective glycemic control. A number of oral glucose lowering
      drugs is now available such as metformin, sulfonylureas, non-sulfonylureas
      secretagogues (metiglinides derivatives), alpha-glucosidases inhibitors, and the
      newest agent: thiazolidinediones (TZD). The possible associations of oral glucose
      lowering drugs for optimal treatment of type 2 diabetes are briefly reviewed. In
      particular, the effects of different classes of drugs on cardiovascular risk
      factors (and particular hypertension and dyslipidemia) and well recognized
      cardiovascular disease markers in type 2 diabetes are analyzed: in this context
      TZD appear the more innovative drugs and have been shown to play a key role in
      the management of hypertension, dyslipidemia, inflammation and endothelial
      disfunction in diabetic patients. The possible adverse effects derived from the
      association of different drug classes are also considered.

PMID- 18078020
TI  - Utilizing enoxaparin in the management of STEMI.
AB  - The use of enoxaparin in conjunction with thrombolysis in ST-elevation acute
      myocardial infarction (STEMI), has been recently investigated in several clinical
      trials. In 8 published open-label studies including about 10,000 patients, in
      which enoxaparin was compared to either placebo or unfractionated heparin (UFH),
      a general superiority of enoxaparin on both reinfarction/recurrent angina and
      patency of the infarct-related artery, was observed. Overall, bleeding rate with
      enoxaparin was higher than with placebo and comparable to UFH, with the exception
      of one study where pre-hospital administration induced a doubled incidence of
      intracranial bleeding in patients older than 75 years. In a recent double-blind,
      randomized, mega-trial including over 20,000 patients, the superior efficacy on
      in-hospital and 30-day adverse cardiac events (namely reinfarction), and
      comparable safety on intracranial bleedings of enoxaparin compared to UFH, was
      definitively proven. In conclusion, initial intravenous bolus of enoxaparin
      followed by twice daily subcutaneous administration for about 1 week should be
      considered instead of intravenous UFH for the treatment of patients with STEMI
      receiving thrombolysis. Along with its easiness of use, not requiring laboratory
      monitoring, the subcutaneous administration of enoxaparin allows extended
      antithrombotic treatment, while permitting early mobilization (and
      rehabilitation) of patients.

PMID- 18078019
TI  - Cardiovascular disease and osteoporosis: balancing risk management.
AB  - In this narrative review of the current literature, we examine the traditional
      risk factors and patient profiles leading to cardiovascular disease and
      osteoporosis. We discuss the interrelationships between risk factors and common
      pathophysiological mechanisms for cardiovascular disease and osteoporosis. We
      evaluate the increasing evidence that supports an association between these
      disabling conditions. We reveal that vascular health appears to have a strong
      effect on skeletal health, and vice versa. We highlight the importance of
      addressing the risk benefit of preventative interventions in both conditions. We
      discuss how both sexes are affected by these chronic conditions and the
      importance of considering the unique risk of the individual. We show that
      habitual physical activity is an effective primary and secondary preventative
      strategy for both cardiovascular disease and osteoporosis. We highlight how a
      holistic approach to the prevention and treatment of these chronic conditions is
      likely warranted.

PMID- 18078021
TI  - Management of intracerebral hemorrhage.
AB  - Currently, intracerebral hemorrhage (ICH) has the highest mortality rate of all
      stroke subtypes (Counsell et al 1995; Qureshi et al 2005). Hematoma growth is a
      principal cause of early neurological deterioration. Prospective and
      retrospective studies indicate that up to 38% hematoma expansion is noted within
      three hours of ICH onset and that hematoma volume is an important predictor of 30
      day mortality (Brott et al 1997; Qureshi et al 2005). This article will review
      current standard of care measures for ICH patients and new research directed at
      early hemostatic therapy and minimally invasive surgery.

PMID- 18078022
TI  - Can combining different risk interventions into a single formulation contribute
      to improved cardiovascular disease risk reduction? The single pill of
      amlodipine/atorvastatin.
AB  - In order to prevent cardiovascular events, it is essential to effectively manage
      overall risk of cardiovascular disease. However, despite guideline
      recommendations to this effect, current management of the major, modifiable
      cardiovascular risk factors such as hypertension and dyslipidemia is disconnected
      and patient adherence to therapy is poor. This is particularly important for
      patients with multiple cardiovascular risk factors, who are often prescribed
      multiple medications. The JEWEL study program investigated the use of single-pill
      amlodipine/atorvastatin as a strategy to improve management of these patients.
      The JEWEL program consisted of two 16-week, international, open-label,
      multicenter, titration-to-goal studies in patients with hypertension and
      dyslipidemia. The two studies differed based on country of enrollment and certain
      tertiary endpoints, but the overall designs were very similar. Patients were
      enrolled from 255 centers across Canada and 13 European countries. The study was
      designed to assess the efficacy, safety, and utility of amlodipine/atorvastatin
      single-pill therapy in a real-world setting. Patients were initiated at a dose of
      amlodipine 5 mg/atorvastatin 10 mg, unless previously treated, and were
      uptitrated as necessary. The primary efficacy parameter was the percentage of
      patients, at different levels of cardiovascular risk, achieving country-specific
      guideline-recommended target levels for blood pressure and lipids. A secondary
      analysis of efficacy measured attainment of the same single goal for blood
      pressure across all study participants (JEWEL I and II) and the same single goal
      for LDL-C across all study participants (JEWEL I and II). The program utilized a
      newly developed questionnaire to gain better understanding of participants'
      beliefs and behaviors towards medical treatment of their multiple risk factors.
      Approximately 2850 patients were enrolled in the program, which was completed in
      August 2005. The JEWEL program assessed the effectiveness of a single pill
      (amlodipine/atorvastatin) in targeting the two principal risk factors for
      cardiovascular disease simultaneously to achieve nationally applicable treatment
      targets in a routine clinical practice setting.

PMID- 18078023
TI  - A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes.
AB  - Type 2 diabetes (T2D) is a progressive disorder with a consistent and steady
      increase in glycosylated hemoglobin (HbA1c) over time associated with enhanced
      risk of micro- and macrovascular complications and a substantial reduction in
      life expectancy. There are three major pathophysiologic abnormalities associated
      with T2D: impaired insulin secretion, excessive hepatic glucose output, and
      insulin resistance in skeletal muscle, liver, and adipose tissue. These defects
      have been treated in clinical praxis by use of oral insulin secretagogues
      (sulfonylureas/ glinides) or insulin, biguanides, and thiazolidinediones (TZDs)
      respectively. Pioglitazone HCL is an insulin sensitizer in the TZD family and
      glimepiride is an insulin secretagogue in the SU family. This article reviews
      mechanisms of action and clinical data behind the use of these two commonly used
      oral hypoglycemic agents with documented efficacy and good safety profile of once
      daily administration, alone or in combination with insulin or metformin, in the
      management of T2D in terms of glycemic and non-glycemic effects, tolerability and
      side effects, and impact on vascular health.

PMID- 18078024
TI  - Colesevelam hydrochloride: reducing atherosclerotic coronary heart disease risk
      factors.
AB  - Colesevelam HCl is a bile acid sequestrant (BAS) which has been specifically
      designed with a unique structure for the purpose of improving tolerability and
      reducing potential drug interactions compared to older BAS, such as
      cholestyramine and colestipol. As a class, BAS are known to reduce cholesterol
      and glucose levels, and to reduce atherosclerotic coronary heart disease (CHD)
      risk as monotherapy, and in combination with other lipid-altering drug therapies.
      Colesevelam HCl has specifically been shown to reduce total and low-density
      lipoprotein (LDL) cholesterol levels, and has been approved as a cholesterol
      lowering drug since year 2000. It has also been shown to reduce glucose levels.
      This discussion reviews mechanisms by which BAS lower cholesterol, and potential
      mechanisms by which BAS lower glucose levels in patients with type 2 diabetes
      mellitus. Finally this paper specifically reviews colesevelam HCl's pharmacology,
      lipid and glucose efficacy, safety/tolerability, and clinical use.

PMID- 18078025
TI  - Macro- and micronutrients in patients with congestive heart failure, particularly
      African-Americans.
AB  - Not all patients with heart failure, defined as a reduced ejection fraction, will
      have an activation of the RAAS, salt and water retention, or the congestive heart
      failure (CHF) syndrome. Beyond this cardiorenal perspective, CHF is accompanied
      by a systemic illness that includes oxidative stress, a proinflammatory
      phenotype, and a wasting of soft tissues and bone. A dyshomeostasis of calcium,
      magnesium, zinc, selenium, and vitamin D contribute to the appearance of
      oxidative stress and to compromised endogenous defenses that combat it. A
      propensity for hypovitaminosis D, given that melanin is a natural sunscreen, and
      for secondary hyperparathyroidism in African-Americans make them more susceptible
      to these systemic manifestations of CHF-a situation which is further threatened
      by the calcium and magnesium wasting that accompanies the secondary aldosteronism
      of CHF and the use of loop diuretics.

PMID- 18078026
TI  - Determinants of outcome in patients eligible for thrombolysis for ischemic
      stroke.
AB  - OBJECTIVES: Eligibility criteria for thrombolysis in ischemic stroke have been
      clearly defined. However, not all eligible patients benefit from this treatment.
      This study aimed to assess the determinants for clinical outcome in consecutive,
      eligible patients with ischemic stroke treated with thrombolysis in a single
      center study. METHODS: Consecutive patients with ischemic stroke were treated
      with tissue plasminogen activator (t-PA) following the established eligibility
      National Institute of Neurological Disorders and Stroke (NINDS) and European
      Stroke Initiative (EUSI) criteria. Risk factors including blood pressure and pre
      treatment glycemia were properly managed. Death and disability at 3 months were
      the study outcomes. Disability was evaluated by the Rankin-scale. Favorable
      outcome was defined as 0-2 and adverse outcome as 3-6 including death. RESULTS:
      Seventy-eight patients were included in the study in a single stroke unit. The
      mean age was 70.9 +/- 13.2 years (range 36-94). Follow-up at 3 months was
      completed in 73 patients. A favorable outcome was observed in 37 patients (50%)
      and adverse outcome in 36 (36%). Nine patients (12.3%) died within 3 months. The
      presence of an occluded carotid artery was a strong predictor for adverse outcome
      (p < 0.0001). A low NIH Stroke Scale-Score (NIHSS) at admission was a associated
      with a favorable outcome, while history of diabetes mellitus led to an
      unfavorable outcome. CONCLUSION: Among patients eligible for thrombolysis, many
      do not benefit from this treatment. These include patients with carotid occlusion
      and diabetes.

PMID- 18078028
TI  - Rates of symptom reoccurrence after endovascular therapy in subclavian artery
      stenosis and prevalence of subclavian artery stenosis prior to coronary artery
      bypass grafting.
AB  - Percutaneous transluminal angioplasty (PTA) and stenting is commonly used to
      treat subclavian artery stenosis (SAS). In this study, the outcomes of 43
      consecutive cases, performed at one institution from October 1997 to October
      2005, were analyzed. Mean stenosis was 84.41% pre-intervention and 6.83% post
      intervention. Five of the procedures were angioplasty alone; 38 were angioplasty
      with stenting. Technical success was achieved in 42 out of 43 patients. The 30
      day mortality rate was 0%. At one-month post intervention, all patients were
      symptom free. Ten patients redeveloped symptoms by one year. Demographic data,
      patient comorbidities, and indication to treat were analyzed. It was found that
      prior coronary intervention led to a statistically significant higher rate of
      symptom reoccurrence (p = 0.036). Additionally, a divergence in the rate of
      symptom reoccurrence based on indication to treat SAS was noted with the highest
      rate of symptom reoccurrence in the pre-coronary artery bypass grafting (CABG)
      group and the lowest rate of symptom reoccurrence in the subclavian steal
      syndrome (SSS) group. The coronary subclavian steal (CSS) group had an
      intermediate rate of symptom reoccurrence. During this time period, 1154 CABGs
      were performed. Flow-limiting stenosis was noted on angiography in 17 of these
      patients, giving pre-CABG prevalence of 1.46%.

PMID- 18078027
TI  - Is general anesthesia a risk for myocardium? Effect of anesthesia on myocardial
      function as assessed by cardiac troponin-i in two different groups (isofluran+N2O
      inhalation and propofol+fentanyl iv anesthesia).
AB  - BACKGROUND AND OBJECTIVES: Peroperative myocardial infarction (MI) is the most
      common cause of morbidity and mortality. What is the role of general anesthesia
      in this process? Is general anesthesia a risk for myocardial infarction? The
      present study was designed to determine whether the measurement of serum levels
      of cardiac troponin I (cTnI), a highly sensitive and specific marker for cardiac
      injury, would help establish the diagnosis of myocardial infarction in two
      different types of anesthesia. METHOD: Elective abdominal hysterectomy was
      planned with the permission of the ethic committee in 40 patients who were 20-45
      years range, in ASA-I group, and have a Goldman Cardiac Risk Index-0. The
      patients were divided into two groups. Isoflurane + N2O was administrated to
      first group, and Propofol + Fentanyl to second group. cTnI levels were determined
      before anesthesia, after induction before surgery and 9 hours after the second
      period respectively. RESULTS: There was no significant difference between the
      groups by the means of demographic properties, hemodynamic parameters and cTnI
      levels, and the cTnI levels were determined under the basal levels in all
      samples. CONCLUSION: General anesthesia is not a risk for myocardial infarction
      to state eliminating risk factors and protection hemodynamia cardiac.

PMID- 18078029
TI  - Magnetic resonance imaging in coronary artery bypass surgery--improvement of
      global and segmental function in patients with severely compromized left
      ventricular function.
AB  - OBJECTIVES: In the present study, patients with severely compromized left
      ventricular function underwent magnetic resonance imaging (MRI) before and after
      coronary artery bypass grafting (CABG). Although improvement of global myocardial
      contractile function has been shown before, we sought to evaluate whether a
      functional contractile improvement may be determinable on a myocardial segmental
      basis after CABG surgery. METHODS: Thirty-three CABG patients with left
      ventricular ejection fraction (LVEF) < or =30% prospectively underwent MRI to
      compare pre- and postoperative functional data. At follow-up, all survivors
      underwent clinical assessment. In 16 patients (three patients died
      perioperatively, 13 could were lost to MRI follow-up because of cardiac
      resynchronization therapy and other reasons) postoperative MRI scanning was
      performed. RESULTS: In-hospital mortality was 9%. At 20 +/- 2 months after
      surgery, New York Heart Association class improved from 3.0 +/- 0.1 to 2.2 +/-
      0.2 (p < 0.01). Left ventricular end-diastolic volumes decreased significantly
      from 229 +/- 14 mL to 189 +/- 19 mL (p < 0.05). LV end-systolic volumes decreased
      significantly from 163 +/- 13 mL to 126 +/- 17 mL (p < 0.05). LVEF improved from
      30 +/- 2% to 36 +/- 3% (p < 0.05). On a segmental basis, 42 out of 875 segments
      (4.8%) had normal function before surgery, at follow-up, 177 segments (20.4%) had
      normal regional function (p < 0.05). CONCLUSIONS: Patients who undergo CABG
      surgery with severely compromized left ventricular function, postoperative MRI
      shows improved global and segmental cardiac function at mid-term follow-up. At
      the same time there is considerable clinical improvement.

PMID- 18078030
TI  - Emergency endovascular repair of acute descending thoracic aortic dissection.
AB  - BACKGROUND: Acute descending thoracic aortic dissection is a life-threatening
      emergency. It is not often considered as the initial diagnosis in patients
      presenting with epigastric pain and could easily be missed in a busy casualty
      department. AIM: This case report is aimed to highlight the feasibility of the
      technique and the need for long-term surveillance following endovascular repair
      of acute thoracic aortic dissection. RESULTS: The patient presented with
      epigastric pain radiating to the interscapular region with a stable hemodynamic
      status. A computerized tomography (CT) scan demonstrated type B thoracic aortic
      dissection of the proximal descending thoracic aorta. A successful endovascular
      repair was carried out with uneventful recovery and follow-up CT scan six years
      after stent-grafting shows satisfactory position of the stent-graft, patent false
      lumen in the abdominal aorta perfusing the right kidney, and progressively
      enlarging diameter of the abdominal aorta. CONCLUSION: Thoracic aortic dissection
      should be considered as a differential diagnosis in patients presenting with
      epigastric and interscapular chest pain. Emergency endovascular repair of acute
      thoracic aortic dissection is feasible and relatively safe. Regular follow-up
      with CT scan is required to evaluate the long-term efficacy and identify the need
      for re-intervention.

PMID- 18078031
TI  - Acute coronary syndrome associated with Churg-Strauss syndrome.
AB  - A 41 -year old female patient was admitted with acute onset of dyspnea and chest
      pain. Previous history revealed asthma, chronic sinusitis and eosinophilic
      proctitis. Electrocardiogram showed anterior ST-segment elevations and inferior
      ST-segment depression. Immediate heart catheterization revealed a distally
      occluded left anterior descending coronary artery, the occlusion being reversible
      after nitroglycerine. Cardiac magnetic resonance imaging was consistent with
      perimyocarditis. Hypereosinophilia and IgE elevation were present and Churg
      strauss syndrome was diagnosed.

PMID- 18078032
TI  - [Effect of nooglutyl on the behavior and memory of SAMP10 mice with genetically
      determined accelerated aging].
AB  - It is established that SAMP10 mice (senescence-accelerated mice prone 10) with
      genetically determined accelerated senescence at an age of 9-month exhibit (in
      comparison to 3-month animals of the same strain) the behavior and memory
      deficits typical of aged animals, namely, reduced locomotor activity elevated
      anxiety, and disturbances of memory trace retrieval. Nooglutyl in a dose of 20
      mg/kg produces a positive effect on the behavior and memory of 9-month old SAMP10
      mice. The observed improvements include optimization of the locomotor activity in
      the open field test, diminished anxiety in elevated plus maze test, and improved
      retrieval of passive avoidance reflex.

PMID- 18078033
TI  - [Studying the nootropic effects of betamecil].
AB  - Comparative study of the effects of methyluracil and betamecil showed that a
      fourfold oral administration of betamecil in a dose of 10 mg/kg leads to a
      considerable increase in the orientation-and-search reaction in the open field
      test. This drug effect is retained for at least one week. Betamecil in doses of
      10 and 100 mg/kg does not virtually alter the rate of conditioning of the food
      seeking reflex with respect to the place in the T-shaped maze test (as compared
      to the control animals. However, certain acceleration of the learning process is
      observed as compared to the animals treated with methyluracil. The chronic
      administration of betamecil (for 18 days) results in improved preservation and
      reproduction of the previously conditioned food-seeking habit. Neither piracetam
      nor methyluracil produced such effects. The results suggest that betamecil in
      indicated doses exhibits a nootropic activity.

PMID- 18078034
TI  - [The acute and subchronic effects of hemantane on [3H]-dopamine reuptake in rat
      striatal synaptosomes ex vivo].
AB  - The ex vivo effects of the new antiparkinsonian drug (adamantane derivative)
      hemantane on the [3H]-dopamine reuptake rate (V) in striatum have been studied
      upon acute and subchronic administration of the drug in Wistar rats. The [3H]
      dopamine reuptake was measured in striatal synaptosomes isolated from rats
      decapitated 1 hour after drug injection (40 mg/kg, i.p.), and in synaptosomes of
      rats treated for 7 days with hemantane (single daily dose, 20 mg/kg, i.p.). The
      acute experiment resulted in a significant (30%) decrease in the apparent Vmax of
      [3H]-dopamine reuptake, while the value of the apparent Km remained unchanged.
      The data obtained indicate that hemantane suppresses the DA transporter function
      within physiological concentration range via noncompetitive mode. In contrast,
      subchronic drug administration increases by 17% the apparent Vmax. These results
      demonstrate the active participation of presynaptic transport mechanism in
      dopamine-positive effects of hemantane.

PMID- 18078035
TI  - [Combined blockade of GluR1 AMPA and NMDA receptors effectively eliminates
      neurological disorders in rats with experimental allergic encephalomyelitis].
AB  - The experimental allergic encephalomyelitis (EAE) developed on the 11 - 12th day
      after inoculation of encephalitogenic mixture in 96% of female Wistar rats in the
      control group. In the majority of control rats, severe EAE with a long duration
      of action prevailed (average cumulative index, 25.6; average duration of illness,
      15.8 days). A course of NMDA-antagonist memantine administration in a doze of 10
      and 20 mg/kg prevented the development of EAE in 10% of rats. In rats with EAE
      (on the average, 12-13 days after the administration of encephalitogenic mixture)
      the drug slightly reduced the severity and duration of neurological disorder: the
      average cumulative index and duration of illness decreased by a factor of 1.4-1.5
      in comparison to the control. The antagonist of NMDA and GluR1 AMPA receptors,
      IEM-1913, upon a course of administration in a doze of 0.1-1 mg/kg prevented the
      EAE development in 23-25% of rats. In the rats with EAE treated with IEM-1913 in
      the maximum doze (1 mg/kg), the EAE developed only after completion of the course
      of drug administration (on the 19-20th day), proceeded quickly (no more than 5
      days), and in the easy form (average cumulative index. 8.3). High efficacy of IEM
      1913 administration in rats with EAE is apparently connected with its
      neuroprotective and antiinflammatory action, which is related, on the one hand,
      to a combined block of NMDA and GluR1 AMPA of receptors in brain and, on the
      other hand, to a reduction of the permeability of BBB for encephalitogenic T
      lymphocytes owing to the blockade of NMDA receptors in BBB.

PMID- 18078036
TI  - [Daphnia magna (straus): a new test object for modeling of dopaminergic
      neurotransmission deficiency induced by the selective neurotoxin 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine].
AB  - The possibility of using Daphnia magna (Straus) hydrobionts as a test object in
      modeling the disturbances of dopaminergic neurotransmission was investigated. The
      toxic action of a selective dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), on D. magna was determined in a broad interval of
      concentrations (from 2 x 10(-5) to 10(-2) M). Plots of the real time of daphnia
      death versus MPTP concentration are presented and the concentration limits of its
      specific activity are evaluated. Experiments on daphnia under the conditions of
      MPTP intoxication were used to study the modulating effects of drugs producing a
      pharmacological correction of dopamine secretion disturbances in mammals. It is
      shown that the exogenous dopamine, muscarinic cholinoblocker pentifine, and
      antioxidant unithiol exhibit a protective action. Reduced glutathione does not
      possess protective properties. It is suggested to use D. magna as a simple and
      informative test object for the modeling of dopaminergic transmission deficiency
      and for the primary screening of various substances intended for the
      pharmacological correction of dopamine transmission disturbances.

PMID- 18078037
TI  - [Therapeutic effect of p-tyrosol on myocardial electric instability induced by
      coronary occlusion].
AB  - In experiments on rats with left coronary artery occlusion, p-tyrosol (20 mg/kg,
      intravenously) showed the ability to decrease myocardial electric instability in
      phase 1b of ventricular arrhythmias: a fraction of rats without arrhythmia was
      increased by 36%, and the mean value of ventricular arrhythmia index exhibited a
      3-fold decrease.

PMID- 18078038
TI  - [Chronic blockade of serotonin transporter promotes restoration of the
      sensitivity of pulmonary vessels to vasoconstrictive agents in rats with
      monocrotaline-induced pulmonary hypertension].
AB  - Dose-dependent change of the reactivity of pulmonary vessels with respect to
      serotonin and phenylephrine were investigated in rats with monocrotaline-induced
      pulmonary hypertension caused by the chronic administration of fluoxetine. It was
      found that the treatment with fluoxetine favors a decrease of the
      vasoconstrictive response in pulmonary vessels. The results suggest that the
      chronic administration of fluoxetine can restore the reactivity of pulmonary
      vessels and eliminate the symptoms of pulmonary hypertension.

PMID- 18078039
TI  - [Hepatoprotective effect of 2-demethoxycarbonyl-2-ethoxycarbonyl-11
      deoxymisoprostol].
AB  - 2-Demethoxycarbonyl-2-ethoxycarbonyl-11-deoxymisoprostol (11-DMP) produces
      antioxidant effect on the models of toxic hepatitis induced by paracetamol and
      carbon tetrachloride. The drug normalizes the lipid peroxidation (LPO) prosess in
      rat liver of the rat and the levels of aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) in the rat blood, thus demonstrating
      hepatoprotective action.

PMID- 18078040
TI  - [Comparative study of the effects of new fluorine-containing pinacidyl analogs on
      bladder contractile function and vessel tone].
AB  - The effects of four new fluorine-containing pinacidyl analogs (FPs) on the
      bladder contractile function in vitro and in vivo, and on the vessel tone in
      vitro were examined. All the four drugs produced a concentration-dependent
      relaxation of isolated rat detrusor strips and isolated aorta rings. The
      contractility inhibition effect of compound FP-5 was decreased by preliminary
      glibenclamide perfusion. This compound also effectively inhibited bladder
      contractility function in vivo.

PMID- 18078041
TI  - [Effect of standardized solution of brine mineral bischofit (MgCL2.6H2O) on the
      antenatal development of rat fetus].
AB  - A standard solution of mineral bischofit has low toxicity and produces a dose
      dependent effect on the antenatal development of rat fetuses. Bischofit in a dose
      of 0.01 ml/kg and 0.1 ml/kg (daily requirement for magnesium ions) increased the
      index of fertility and the quality of embryonal development in rats. The index of
      fertility was reduced and fetal skeleton formation was inhibited after the
      administration of bischofit in a dose of 1.0 ml/kg.

PMID- 18078042
TI  - [Myelotoxicity of paclitaxel (mitotax)].
AB  - Paclitaxel (single intravenous injection in a maximum tolerated dose of 4.6
      mg/kg) to white outbred rats causes bone marrow hypoplasia, increased granulocyte
      and erythroid cell mitosis (metaphase-anaphase transition), and moderate
      pancytopenia developments in peripheral blood (hypoplastic anemia, deep, short
      term neutropenia, lymphopenia and thrombocytopenia) in the first hours after
      injection. A considerable increase of polyploidy (4n) cells and a moderate
      increase in the structural changes (chromatid deletions) of chromosomes was
      observed on bone marrow metaphase plates in 24 h. The drug introduction causes
      earlier increase in the rate of thymus cells mitosis, a growth in the number of
      thymocytes with apoptosis signs, and a moderate decrease in the thymus and spleen
      weight. All changes are reversible. Long-term (90 days after injection)
      observation revealed decreased lymphocyte count in the peripheral blood and bone
      marrow and earlier thymus involution.

PMID- 18078043
TI  - [Nootropes (cognition enhancers) and neuroprotectors].
AB  - The paper reviews the existing and future nootropic drugs (cognition enhancers)
      with different mechanisms of action and heterogenous chemical structures, which
      have been developed on the basis of knowledge of the mechanisms of learning,
      memory and forgetting, as well as degenerative processes in aging brain and
      disease-associated cognitive impairments. These agents influence on acetylcholine
      , glutamate-, GABA-, 5-HT-, dopamine-, histamine-, adenosine-, phosphodiesterase
      , neurotrophic- systems, and neurohormones. Neuropeptides and their analogs,
      blood flow enhancers, calcium-channel blockers, antioxidants and vitamins and
      herbal preparations, and some other agents improving cerebral metabolism and
      influencing the neurodegeneracy involved in Alzheimer's disease are considered.
      An original classification of cognition enhancers, based on mechanisms of their
      action, includes more than 200 drugs in current use and those currently under
      development.

PMID- 18078044
TI  - [Hippocampus: a target for cognition enhancers].
AB  - According to recent data, limbic brain structure (hippocampus) may be important
      target for the action of different groups of cognitive enhancers (nootropic
      drugs). Their specific influence on the cognitive processes is correlated with
      the normalization of metabolic and morphological disturbances in hippocampal
      neurons.

PMID- 18078045
TI  - [Selective and specific reduction in the heart rate: a promising direction in the
      creation of new cardiovascular drugs].
AB  - Numerous data indicate that a high heart rater (HR) is a risk factor in various
      cardiovascular diseases. The effects of HR on the energetics of myocardium,
      contractility function, collateral coronary blood circulation, and atherogenesis
      are considered. A special attention is devoted to specific bradycardic drugs and
      their mechanisms of action on the electrophysiological processes in the sinus
      node and on the HR. The new drug ivabradin (a specific selective blocker of the
      If current) can produce a bradycardic effect and exhibit a pronounced
      antiischemic action on the myocardium. The creation of such drugs offers an
      alternative to beta-adrenoblockers and calcium antagonists and opens new
      possibilities in the pharmacological protection of ischemized myocardium.

PMID- 18078046
TI  - [Indications for optimized refractive keratoablation. Communication 1. Dependence
      on the grade of myopia and baseline high-order aberrations].
AB  - The authors made a detailed comparative analysis of the aberration pattern of
      patients before and after aspheric individualized keratoablation (ORK-CAM) and
      the LASIK operation by routine technology, by taking into account the grade of
      correctable myopia and the size of baseline high-order aberrations (HOA).
      Investigations were made in 2 groups: 1) 20 patients (39 eyes) who had undergone
      routine ablation (a study group); 2) 19 patients (38 eyes) who had aspheric
      individualized keratoablation (a control group). The findings suggest that
      individualized aspheric keratoablation is effective in patients with mild and
      moderate myopia with varying baseline HOA. In addition, a relationship was found
      between the results of standard and optimized correction and one more key
      parameter of the aberration pattern, namely the magnitude of 4th-order spherical
      aberration that should be also taken into account on choosing an eximer laser
      correction technology. There is an outstanding question whether it is expedient
      to perform ORK-CAM in patients with high-grade myopia. The above problems require
      that further studies be continued and will be considered in part 2 of the present
      investigation.

PMID- 18078047
TI  - [Indications for optimized refractive keratoablation. Communication 2. Dependence
      on baseline spherical aberrations].
AB  - The authors made a detailed comparative analysis of the aberration pattern of
      patients before and after aspheric individualized keratoablation (ORK-CAM) and
      the LASIK operation by routine technology, by taking into account the magnitude
      of 4th-order spherical aberration. Investigations were made in 2 groups: 1) 20
      patients (39 eyes) who had undergone routine ablation (a study group); 2) 19
      patients (38 eyes) who had aspheric individualized keratoablation (a control
      group). The detailed comparative analysis of the aberration pattern in patients
      after eximer laser correction by different technologies yielded major criteria
      predetermining the choice of an eximer laser correction technology. Indications
      for routine and individualized aspheric keratoablation are defined. Further
      studies of the impact of high-order aberrations on different visual functions are
      required to solve the vexed questions whether it is aberrationally expedient to
      choose laser correction. Ophthalmo-ergonomic studies should be also performed to
      provide a clinical verification of the consistency of the proposed concept of the
      indications and the choice of the optimal technology of eximer laser correction.

PMID- 18078048
TI  - [Reconstructive laser surgical treatment for posttraumatic traction
      ciliochoroidal detachment].
AB  - To treat patients with eye injuries remains a topical problem due to the high
      incidence of this type of pathology and the severity of clinical outcomes.
      Ciliochoroidal detachment (CCD) occurring in 1-9% of the victims is one of the
      most common complications of mechanical eye injury. The purpose of the study was
      to evaluate the efficiency of pathogenetically substantiated technology for a
      combined laser surgical reparative intervention in posttraumatic traction CCD.
      The results of treatment were analyzed in 70 patients with posttraumatic traction
      detachment of the choroid and ciliary body. There was evidence for the need for
      vitrectomy and lensectomy in combination with posterior sclerectomy to eliminate
      traction posttraumatic CCD.

PMID- 18078049
TI  - [Simplified modification of tunnel cataract extraction].

PMID- 18078050
TI  - [Echographic determination of the extent of intraocular tumors].
AB  - The capacities of current ultrasound technologies in determining the extent of
      intraocular tumors were clinically studied. The proposed algorithm of ultrasound
      study of intraocular tumors allows for not only making the exact measurements of
      a neoplasm, but also for determining the three-dimensional configuration of an
      object within the eye.

PMID- 18078051
TI  - [Intraocular and spectacular chromatographic correction in opacities of the
      posterior lenticular capsule].
AB  - Intraocular and spectacular chromatographic correction was comparatively studied
      by examining blindness and spatial contrast sensitivities in 81 patients (116
      eyes) after implantation of achromatic and chromatic hydrophobic acrylic
      intraocular lenses (IOL). Spectacular chromatic correction with yellow filters
      was additionally used in patients with achromatic IOL. 1.5-2 years after surgery
      for developed posterior capsular opacities, higher ergonomic vales remained in
      patients with intraocular chromatic correction than in those who had achromatic
      IOL and had undergone additional spectacular chromatic correction.

PMID- 18078052
TI  - [Clinical efficacy of jointless therapeutic amnion surfacing of the cornea in its
      diseases and injury].
AB  - The surgical treatment option for corneal diseases and injury - therapeutic
      silicone-dried amnion surfacing is widely used in ophthalmological care. The
      Voronezh Regional Clinical Eye Clinic has developed and introduced into a
      therapeutic process an alternative option, namely jointless therapeutic amnion
      corneal surfacing, by using a soft contact lens and viscoelastic. This option is
      easy-to-use and enables psychoemotional stress associated with a surgical
      intervention to be avoided. It may be employed in patients with severe somatic
      diseases, its clinical effectiveness being retained.

PMID- 18078053
TI  - [Assessment of the clinical and functional results of laser coagulation of
      retinal drusen in the central zone of the eye grounds].
AB  - Macular drusen are known to be a major risk factor of age-related macular
      degeneration (ARMD) of the retina. The use of laser coagulation of macular drusen
      to prevent the progression of a dystrophic process remains to be disputable
      question so far. This paper presents the clinical and functional results of laser
      coagulation of macular drusen in 30 patients with bilateral retinal ARMD. The
      routine ophthalmological study, photorecording, fluorescence angiography of the
      fundus of the eye, optic coherent tomography, and electrophysiological studies
      indicated macular drusen regression, increased visual acuity, and better
      electrophysiological parameters. Choriodal neovascularization and exudative
      complications did not develop in both the early and late follow-up periods.

PMID- 18078054
TI  - [Feasibilities of photodynamic therapy in the treatment of corneal mycotic
      lesions: an experimental study].
AB  - The paper presents the results of studying the photofungicidal activity of a
      photosens (octacationic phthalocyanine) in the in vitro and in vivo systems.
      Cultured Candida guilliermondii were employed in in vitro investigations. The
      single combined action of octacationic phthalocyanine at a concentration of up to
      1 microM and laser irradiation at a wavelength of 675 nm were established to
      allow the high activation (up to 100%) of yeast fungi to be achieved in the in
      vitro system. In vivo investigations were performed on 14 rabbits (28 eyes) with
      induced keratomycosis. In the first series, fluorescent diagnosis of photosens
      accumulation in the pathological corneal areas was made in 9 (18 eyes). Based on
      the data obtained in the second series of experiments, the authors examined the
      feasibilities of photodynamic therapy for corneal mycotic lesions with the above
      photosensitizer in 5 rabbits (10 eyes).

PMID- 18078055
TI  - [Changes in an electroretinogram and biochemical parameters of tear in simulated
      rabbit retinal ischemia].
AB  - The pattern of functional impairments and the antioxidative and antiproteolytic
      status of tear were studied, by experimentally simulating retinal ischemia in
      rabbits and during treatment with Selecarten. Simulated retinal ischemia resulted
      in the development of persistent (up to 3 weeks) retinal electrogenetic disorder.
      Selecarten instillations produced a moderate neuroprotective effect, by
      positively affecting retinal function early after ischemia stimulation and
      accelerated the recovery of retinal electrogenesis late after laser coagulation
      of retinal vessels. The altered metabolic processes were characterized by an
      increase in the tear antiproteolytic potential. The antioxidative activity and
      the activity of a2-macroglobulin proteolysis inhibitor increased in the tears of
      Selecarten-treated rabbits.

PMID- 18078056
TI  - [Impact of ozone therapy on the electrophysiological parameters of the retina in
      patients operated on for its rhegmatogenous detachment].
AB  - The impact of ozone therapy on changes in the data of maximum combined
      electroretinography (ERG), macular ERG (MERG), and rhythmic ERG (RERG) at 12, 32,
      and 40 Hz was studied in the rehabilitative period in patients operated on for
      rhegmatogenous retinal detachment. The integral and local glial indices K(g) and
      K(c) were calculated. Studies were conducted before, within 1 week and 1 and 2
      months after a course of therapy. With ozone therapy, ERG and RERG depended on
      the specific features of changes available in the fundus of the eye before
      surgery. In the early rehabilitative period after surgery (circlage with
      subretinal fluid removal), ozone therapy normalized the glial indices, by
      decreasing the supernormal activity of Muller's glial cells and drastically
      increasing their reduced activity. The maximum effect was revealed for the
      function of phororeceptors (except for the eyes showing pronounced myopic
      dystrophic changes in the fundus). There were increases in MERG, ERG b-wave, and
      low-frequency RERG by 12 Hz, i.e. improved functions of the macular region and
      distal neurons of the retinal rod cell system. A latent period was established
      for the manifestation of a positive effect of ozonwe therapy on the functional of
      neurons of the internal retinal nuclear layer, as evidenced by RERG changes.
      Ozone therapy positively affect retinal electrogenesis in cases of total retinal
      detachment accompanied by a pronounced reduction in the glial index Kg before
      surgery. The therapy was found to have a positive impact on the functional
      activity of the retina of pair eyes, by developing within a one-moth latent
      period.

PMID- 18078057
TI  - [Study of the expression of embryonal choroidal tissue-specific markers].
AB  - The authors used the human embryonal eye to conduct immunohistochemical studies
      employing the tissue-specific markers of the melanocytic series (HMB45,
      tyrosinase, melanin A, and MITF) and neuronal differentiation (S100), as well as
      the markers of intermediate and muscular filaments (vimentin, desmin, smooth
      muscle actin). The nature of antigen expression was analyzed in different
      structures and portions of the vascular tract of the eye. The findings unveil the
      possibility of differentiating the vascular tract tumors of various genesis and
      their sites, by applying a plate containing the above markers.

PMID- 18078058
TI  - [Study of a role of the expression of a transmembranous CD117/C-Kit receptor in
      the progression of uveal melanomas].
AB  - The authors studied the expression of the protooncogen receptor involved in the
      regulation of major cell cycle processes in uveal melanoma. The studies performed
      by a highly sensitive immunohistochemical technique. The findings have allowed
      the authors to state that the membranous CD117/C-Kit receptor plays an important
      role in the progression of uveal melanomas. It is suggested that the use of the
      new drug Glivec is promising in treating uveal melanoma.

PMID- 18078059
TI  - [Clinical forms of corneal abnormalities in atopic keratoconjunctivitis].
AB  - Atopic keratoconjunctivitis (AKC) is presently considered as an individual
      nosological entity of ocular allergosis, which is associated with the systemic
      disease - atopic dermatitis. The clinical features of corneal lesions were
      studied in 40 patients with AKC. Those associated with the systemic pattern of an
      atopic process as a severe form of ocular allergosis were revealed. A
      classification of the clinical forms of corneal lesions in AKC as limbitis,
      epithelial microerosions, epithelial keratopathy, superficial keratitis in mild
      forms of the disease, is presented. The severe forms of AKC were characterized by
      corneal manifestations: extensive keratopathy, stromal keratitis with
      neovascularization without ulceration, corneal infiltrates and ulcers of
      bacterial and herpetic etiology.

PMID- 18078060
TI  - [Optical aberrations of the eye and feasibilities of their compensation by means
      of contact lenses and surgical interventions in primary ametropias and
      keratoconus].

PMID- 18078061
TI  - [Use of thrombolytic agents during invasive treatments for retinal vascular
      occlusions].

PMID- 18078062
TI  - [Experience with vascular endothelial growth factor inhibitors used in
      ophthalmologic care].

PMID- 18078063
TI  - [Natriuretic peptides].
AB  - Natriuretic peptides are the family of structurally related peptides involved
      into regulation of volume and blood pressure, water and electrolyte metabolism,
      and also cell proliferation. Their effects are mediated via three types of
      membrane receptors. Two of them are receptor guanylate cyclases, which catalyze
      cGMP formation (from GTP), second intracellular messenger responsible for
      realization of regulatory signals of these hormones. Genetic defects resulting in
      deficit of natriuretic peptides or their functionally active receptors in
      transgenic mice cause development of arterial hypertension, myocardial
      hypertrophy and increased mortality in early age.

PMID- 18078064
TI  - [Blood deoxyribonuclease activity in health and diseases].
AB  - The data about deoxyribonuclease activity in blood of healthy donors and patients
      with malignant and autoimmune diseases are described. Methodological aspects of
      the analysis of DNase activity and factors which interfere with DNase activity in
      blood are discussed.

PMID- 18078065
TI  - [Biological activity of phytosterols and their derivatives].
AB  - The review deals with results of recent studies on biological activity of C29-
      and C28-sterols of plant origin (phytosterols) in mammals and in cultured
      mammalian cells. The review considers the following problems: phytosterols and
      nutrition; phytosterols and cholesterol level; phytosterols and intestinal
      absorption of lipids; the role of phytosterols in lipid metabolism regulation;
      phytosterols and mammalian cells in culture; products of phytosterols oxydation;
      phytoecdysteroids and induced gene expression.

PMID- 18078066
TI  - [Computer-aided design of polyketides with the required properties].
AB  - We propose an approach to rational design of new polyketides with the required
      spectrum of biological activity. We developed BioGenPharm software for generation
      of polyketide combinatorial libraries, prediction of activity spectra for the
      generated structures and selection of molecules with the required properties on
      the basis of user defined input parameters and selection criteria. For prediction
      of polyketide activity spectra we used PASS algorithm
      (http://www.ibmc.msk.ru/PASS). Validation of PASS prediction ability for
      polyketides was performed vs. the evaluation set containing 242 natural
      macrolides from the Dictionary of Natural Products. The mean prediction accuracy
      was 75,5%. The problem of choice of cutting points for probability of the
      presence of activity (Pa), which provide optimal combination of such parameters
      as sensitivity, specificity, concordance was considered. Applicability of the
      described method has been illustrated by generation of a virtual library of the
      erythromycin analogues and selection substances for which the probability of
      hepatotoxic action is low.

PMID- 18078067
TI  - [Biodegradation of 125I-labeled monoclonal antibodies after introvenous
      administration to rats with experimental C6 glioma].
AB  - Employment of radiolabeled antibodies in biological studies allows their specific
      accumulation in organs and tissues to be detected. However, stability of such
      labeled antibodies depends on both the method of labeling and particular
      experimental conditions. Therefore, stability of labeled antibodies should be
      determined in every particular experiment. The present paper describes the
      results obtained in the study of the radiochemical purity and stability of the
      125I-labeled conjugates of antibodies to the gliofibrillary acidic protein
      (GFAP), endothelial antigen AMVB1, and non-specific mouse IgG immediately after
      their synthesis and at various time points after intravenous administration to
      rats with experimental C6 glioma. Their stability was determined in the samples
      of blood, brain, liver, spleen, and kidney by precipitation with trichloroacetic
      acid. Electrophoretic analysis, thin-layer chromatography, and
      immunohistochemical tests have proved the radiochemical purity, immunochemical
      competence, and stability of the labeled antibodies in vivo.

PMID- 18078068
TI  - [Phospholipid composition of erythrocyte membranes under conditions of
      postmyocardial infarction cardiosclerosis].
AB  - Changes in phospholipid composition of the erythrocyte membranes have been
      studied in experimental postmyocardial infarction cardiosclerosis. Erythrocyte
      membranes from animals with cardiosclerosis formed after experimantal occlusions
      of coronary arteries were characterized by significant decrease of a minor
      phospholipid, phosphatydylinositol (by more than 40%) and the increase of the
      major phospholipid, phosphatydylethanolamine. There was high content of lipid
      peroxidation products, malondialdehyde and conjugated dienes and the decrease in
      the activity of antioxidant enzymes, catalase and superoxide dismutase in blood
      serum of these animals. We have concluded the formation of postmyocardial
      infarction cardiosclerosis is accompanied by the increase of free radical
      reactions. This causes changes in phospholipid composition of cell membranes and
      the decrease of compensatory capacities of the enzymatic antioxidant system.
      These changes form a metabolic background, [corrected] which can influence
      cardiac remodelling properties.

PMID- 18078069
TI  - [Study of the binding of nuclear proteins from Plasmodium berghei strains with
      different chloroquine sensitivity to oligonucleotides corresponding to regulatory
      elements of multidrug resistance (mdr1) gene].
AB  - Using electrophoretic mobility shift assay we first revealed in the nuclear
      extracts of the rodent malaria parasite Plasmodium berghei (P. berghei) proteins,
      which bind specifically to the double-stranded oligonucleotides reproducing the
      binding sites of the transcription factors of AP1 family, NF-IL6 and SP1 involved
      in the up-regulation of human multidrug resistance (mdr1) gene and to the
      oligonucleotide corresponding to the element responsive for the stimulation by
      serum (SRE). The nuclear proteins isolated from the P. berghei strains with
      various chloroquine sensitivity bound differently to the most of the
      oligonucleotide probes used. Mutations in the consensus sequences of AP1, NF-IL6
      and SRE led to the loss of some DNA-protein complexes, suggesting the existence
      of malaria parasite nuclear proteins, whose DNA-binding domains are similar to
      DNA-binding domains of NF-IL6, SRF1, and AP1 family members. These proteins
      exhibit greater activities in chloroquine resistant strains. The results obtained
      denote profound alterations in the plasmodium regulatory apparatus occurred as
      the result of selection on chloroquine resistance.

PMID- 18078070
TI  - [Polyelectrolyte microcapsules as systems for delivery of biologically active
      substances].
AB  - Novel biodegradable microcapsules for delivery of biologically active substances
      (BAS) were prepared by layer-by-layer (LbL) adsorption of oppositely charged
      polyelectrolytes, namely sodium alginate (Alg) and poly-L-lysine (PLL). To
      immobilize these BAS, porous spherical CaCO3 microparticles were used as
      templates. The templates (cores) were coated with several layers of oppositely
      charged polyelectrolytes forming shell on a core surface. The core-shell
      microparticles were converted into hollow microcapsules by a core dissolution
      after an EDTA treatment. Mild conditions for microcapsule fabrication allow to
      perform an entrapment of various biomolecules while keeping their bioactivity.
      Biocompatibility and biodegradable capability of the polyelectrolytes give a
      possibility to use the microcapsules as the target delivery systems. Chymotrypsin
      (Chym) entrapped into the microcapsules was used as a model enzyme. The
      immobilized enzyme was found to keep about 86% of the activity compared to a
      native Chym. The obtained microcapsules were stable at an acidic medium while
      they could be easily decomposed by trypsin treatment at an slightly alkaline
      medium. Chym was shown to be active after being released from the microcapsules
      decomposed by trypsin treatment. Thus, the microcapsules prepared by the LbL -
      technique can be used for the development of new type of BAS delivery systems in
      humans and animals.

PMID- 18078071
TI  - [Substituted aminophenols and flavonoids as potential components for test-systems
      of total antioxidant activity].
AB  - A comparative kinetic study of ortho-phenylenediamine (PDA) oxidation in the
      "pseudoperoxidase" system Methemalbumin-H2O2 in the presence of 2-amino-4-tret
      butylphenol (ATBP), 2-amino-4,6-di-tret-butylphenol (ADTBP) and its four N-acyl
      derivates, as well as flavonoids (quercetin, morin, silibin, hesperidin and
      naringin) has been carried out under standart conditions at 20 degrees C in
      phosphate buffered saline, pH 7.4, containing 5.25% ethanol and DMFA. ATBP, ADTBP
      and two its N-acyl-derivatives as well as all five flavonoids inhibited with
      different efficiency the PDA oxidation characterized in terms of the inhibition
      constants, K(i), M, or the percent of inhibition degree at the maximal taking
      concentrations of these inhibitors. Most effective antioxidants were quercetin
      (K(i) = 7.7x10(-5) M) and ATBP (K(i) = 1.26x10(-4) M). Using these
      characteristics and other necessary criteria, the pairs PDA-quercetin and PDA
      ATBP were proposed for a practical application in the test-systems for total
      antioxidant activity of biological objects.

PMID- 18078072
TI  - [Assessment of some oxidative stress parameters in bronchial asthma patients
      beyond add-on selenium supplementation].
AB  - The goal of this study was to investigate the effect of selenium deficit
      replenishment in patients with bronchial asthma (BA) on manifestations of
      oxidative stress and conditions of the antioxidant system (AOS). The need of
      correction of selenium deficit in BA-patient is determined by the increased needs
      in antioxidants due to chronic inflammatory process responcible for pathogenesis
      of BA. Latvia and also Eastern Finland, Byelorussia, some regions of Ukraine,
      some regions of the NorthWestern Russia, New Zealand belong to endemic areas with
      marked selen deficit in soils and foodstuff. Twenty patients (7 men and 13 women)
      with selen deficit and verified diagnosis of BA have been examined. In addition
      to basic therapy all patients received organic selenium SelenoPRECISE,
      ("PharmaNord") 200 microg daily for 16 weeks. This caused statistically
      significant increase of plasma selenium from 50.94+/-7.58 microg/l to 63.59+/
      10.87 microg/l (p<0.001), the increase of selenium-dependent glutathione
      peroxidase (from 38.64+/-10.72 U/g Hb to 58.57+/-14.64 U/g Hb, p<0.001).
      Treatment of patients with selenium also normalized parameters charecterizing
      oxidative stress (chemiluminescence). The use of selenium in addition to basic
      therapy allows to abolish or alternate manifestations of oxidative stress by
      correcting the antioxidant system.

PMID- 18078073
TI  - [Functional activity of phagocytes of bronchoalveolar lavage in patients with
      fibro-cavernosis and infiltrative pulmonary tuberculosis].
AB  - Functional activity of the bronchoalveolar lavage fluid (BALF) phagocytes was
      studied in 33 and 16 patients with fibro-cavernosis (FC) and infiltrative (I)
      pulmonary tuberculosis (PT), respectively. Complex examination of BALF, alveolar
      macrophages (AM) and neutrophils (N) sedimented from BALF revealed
      interrelationship between functional activity of the cells and the form of PT.
      Higher activities in BALF of neopterin and elastase mainly secreted by activated
      AM and N respectively, reflect a higher secretory activity of both types of cells
      in FC - PT. These patients are also characterized by more pronounced bactericide
      activity of Ns, which significantly correlates with adenosine deaminase (ADA)
      activity. It is suggested that changes in BALF of various biochemical parameters
      examined (neopterin, elastase, ADA and its isoenzymes, 2-deoxyADA) and
      bactericide activity of the sedimented cells represent are the consequences of
      differend sides of BALF phagocytes functioning. According to modem notions about
      the mechanisms of their regulation different intercellular relations are
      suggested in different form of PT.

PMID- 18078074
TI  - [Distribution of mutations of acid beta-D-glucosidase gene (GBA) among 68 Russian
      patients with Gaucher's disease].
AB  - Gaucher disease (GD) is the most frequent lysosomal storage disease presenting in
      all populations. Mutations in the acid beta-D-glucosidase gene (GBA) cause
      development of GD, resulting in a decrease or full loss of activity of this
      enzyme. We report here the results of the molecular-genetic analysis in 68
      Russian GD patients from 65 families with the three types of the disease. We have
      identified 126 mutation alleles from 136 investigate alleles. In addition to
      known mutations p.N370S, c.1263-1317del (del55), p.L444P, p.R463C, Rec NciI, we
      identified rare mutations p.R120W, p.R170C, p.W184R, p.G202R, Rec C, presenting
      in other populations and mutations p.P236T, p.L249Q, p.L288P, p.P319S, p.V352M,
      p.W381X, p.A384D which are had not been described before.

PMID- 18078075
TI  - [Ubiquitin causes selective increase in the sensitivity of rat brain
      mitochondrial monoamine oxidases to various proteases].
AB  - Incubation of rat brain mitochondria with ubiquitin and ATP followed by
      subsequent mitochondria sedimentation was accompanied by reduction of ubiquitin
      content in the supernatant. This decrease was more pronounced in the presence of
      ATP-regenerating system in the incubation medium (creatine phosphate/creatine
      phosphokinase). This ubiquitin incorporation into brain mitochondria observed
      only in the presence of ATP in the incubation medium increased sensitivity of
      monoamine oxidases (MAO) A and B to proteolytic inactivation by trypsin and
      papain, respectively. (Ubiquitin did not influence sensitivity of MAO B to
      trypsin and MAO A to papain). The data obtained suggest that ubiquitin
      incorporation into rat brain mitochondria increases susceptibility of MAOs to
      certain exogenous proteases, however, it remains unclear whether these changes
      stem from direct MAO-ubiquitin conjugation or reflect alterations in the membrane
      environment of these enzymes.

PMID- 18078076
TI  - [Preoperative assessment of myocardial ischemia in thoracic surgery for lung
      cancer].
AB  - BACKGROUND: Morbidity of myocardial ischemia in the thoracic surgery for lung
      cancer has been reported in the literatures, although, the risk of myocardial
      ischemia is not well identified preoperatively. OBJECTIVES: The aim of this study
      was to describe the prevalence of severe coronary stenosis in the thoracic
      surgery for lung cancer. METHODS: From January 2004 to December 2006, data were
      collected concerning 175 consecutive patients underwent lung resection for lung
      cancer. Prior to the surgery, we performed coronary angiography on the patients
      with either ischemic change in the exercise electrocardiogram (ECG) testing or
      comorbid conditions (current or previous smoking, hypertention, diabetes
      mellitus, hyperlipidemia or history of chest pain). RESULTS: Fifty-eight (33%)
      patients underwent coronary angiography. Coronary stenosis was detected in 19
      patients (10.9%), including 6 patients (3.4%) with severe stenosis. These 6
      patients received percutaneous coronary intervention or coronary artery bypass
      grafting prior to the lung resection, which resulted in no incidence of
      perioperative myocardial ischemia. Three of 6 patients with severe stenosis were
      negative for ischemic changes in exercise ECG testing. CONCLUSION: The prevalence
      of severe coronary stenosis is 3.4%, which is supposed to indicate the risk of
      perioperative myocardial ischemia in the thoracic surgery for lung cancer.

PMID- 18078077
TI  - [The saccular coronary aneurysm associated with coronary artery to pulmonary
      artery fistulae].
AB  - Coronary artery fistulae are relatively rare congenital anomalies. Those
      associated with saccular coronary artery aneurysms are even rarer. Including the
      current case, only 65 such cases have been reported in Japan. A 62-year-old
      female was admitted to our hospital for evaluation of abnormal shadow on the
      chest X-ray. The enhanced chest computed tomography (CT) scan demonstrated a
      giant saccular coronary aneurysm on the left side of the pulmonary artery. Multi
      detector row CT (MDCT) scan demonstrated the coronary artery aneurysm was
      connected to the left anterior descending artery. Coronary angiography revealed 2
      aneurysms with bilateral coronary artery to pulmonary artery fistulae. The
      patient underwent aneurysmectomy and ligation of fistulae under cardiopulomonary
      bypass. The postoperative course was uneventful and postoperative coronary
      angiography revealed complete resection of the aneurysms and only slight blood
      flow through the fistulae. She was discharged on the 10th postoperative day.

PMID- 18078078
TI  - [Surgical repair of traumatic rupture of the discending aorta through 'L'
      thoracotomy].
AB  - Acute blunt aortic rupture occurs frequently at the aortic isthmus and emergency
      operation is usually required. A 33-year-old man was suffered with blunt
      traumatic thoracic aortic injury caused by traffic accident and emergency
      operation was performed due to hemodynamic instability. The patient was operated
      through 'L'-thoracotomy (upper part sternotomy and antero-lateral thoracotomy).
      Cardiopulmonary bypass was initiated with right femoral vein drainage and right
      femoral arterial return and converted to standard cardiopulmonary bypass with the
      ascending aorta return and right atrium appendage drainage when the discending
      aorta was re-ruptured. It stabilized the circulation of upper body, especially
      brain. The post-operative course was uneventful. The 'L'-thoracotomy can provide
      good operative exposure for the aortic isthmus and stabilize the circulation of
      the brain with standard cardiopulmonary bypass and clamping the descending aorta.

PMID- 18078079
TI  - [Cardiac angiosarcoma with diagnostic difficulty].
AB  - We report a case of cardiac angiosarcoma of the right atrium. A 20-year-old woman
      was admitted to the Kyoto Prefectural University of Medicine with severe chest
      pain and dyspnea. A cardiac tumor was diagnosed by computed tomography (CT),
      echocardiography, and cinecardiography. The tumor marker CA125 was 293 U/ml
      (normal : <35 U/ml). Therefore a CT-guided transthoracic needle biopsy under CT
      fluoroscopic guidance for definitive diagnosis was performed after obtaining the
      patient's informed consent. Pathohistologically, the tumor was diagnosed as a
      cardiac angiosarcoma. The use of an intravenous infusion of contrast material
      contributed greatly to clear visualization of the tumor margin and cardiac lumen
      and assisted in easily and correctly advancing the needle toward the tumor.
      Moreover, tumor marker CA125 was a good indicator of therapeutic efficacy.

PMID- 18078080
TI  - [Exposure for harvesting internal mammary artery grafts].
AB  - Inflated lungs often disturb the harvesting of internal mammary artery grafts. We
      employ a Universal Stabilizer Arm and Aortic Valve Assistant (Estech Corporation,
      Danville) to push the mediastinal pleura and the lung away from the upper part of
      the mediastinum. This system can be attached to any type of retractor and has
      excellent flexibility. Its use provides good exposure for harvesting the internal
      mammary artery.

PMID- 18078081
TI  - [Mitral valve repair in a patient with a porcelain ascending aorta].
AB  - A 78-year-old patient with heavily calcified ascending aorta underwent mitral
      valve repair for mitral valve regurgitation. Chordal replacement with expanded
      polytetrafluoroethylene (ePTFE) loop technique was done under endo aortic clamp
      with a balloon catheter. He was discharged from the hospital on the 24th
      postoperative day without any major complications. Endo aortic clamp is thought
      to be a useful technique for a case with heavily calcified aorta.

PMID- 18078082
TI  - [Mitral valve repair with concomitant coronary bypass for partial rupture of an
      anterior papillary muscle].
AB  - We report a case of severe mitral regurgitation due to partial rupture of an
      anterior papillary muscle. A 63-year-old man was admitted to a hospital with
      heart failure. He was treated with diuretic agents effectively. Echocardiography
      demonstrated severe mitral regurgitation with prolapse of posterior leaflet and
      small mass-like structure on the prolapsed segment that was diagnosed the
      thickened leaflet. Coronary angiography revealed total occlusion of left anterior
      descending artery (LAD) filled with good collateral from right posterior
      descending artery and severe diffuse stenosis of circumflex artery (Cx). The
      patient underwent surgery on the 33rd day after admission with heart failure. At
      surgery, we recognized rupture of one of the heads of anterior papillary muscle
      that was entangled in chordae of the prolapsed segment. Mitral valve repair and
      coronary revascularization to LAD and Cx was successfully performed. His
      postoperative course was uneventful, and he was discharged on the 28th
      postoperative day.

PMID- 18078083
TI  - [Primary spontaneous pneumomediastinum].
AB  - We report 5 cases of spontaneous pneumomediastinum. They were 4 men and 1 female
      with a mean age of 17 (14-25). Four patients developed sport-related
      pneumomediastinum and 1 patient had a karaoke-related condition. Primary
      spontaneous pneumomediasinum is a rare condition. In addition, there is no
      previous report describing karaoke-related spontaneous pneumomediastinum. Each of
      the patients experienced chest pain and/or neck pain before consulting our
      hospital. Chest roentgenogram and chest computed tomography showed
      pneumomediastinum without esophageal or tracheal injury. Four patients did not
      require hospitalization, but 1 patient was necessary to hospitalize for 7 days
      because of severe chest and neck pain. None of these 5 patients has had any
      recurrence for more than 1 year. Differentiating this entity from other diseases
      involving anterior chest pain is important.

PMID- 18078084
TI  - [Peripheral small squamous cell carcinoma (9 mm) of the lung with metastasis to
      mediastinal lymph nodes].
AB  - A 61-year-old man was pointed out a small peripheral lung nodule and mediastinal
      lymph node swelling on the chest computed tomography (CT). At the operation, it
      was diagnosed squamous cell carcinoma and right upper lobectomy and nodal
      dissection were done. The tumor was 9 mm in size and diagnosed as well
      differentiated squamous cell carcinoma with metastasis to mediastinal lymph
      nodes. Postoperative radiotherapy was done (50 Gy). The patient is doing well
      without apparent recurrence 33 months after surgery. We reported a case of
      peripheral small squamous cell carcinoma (9 mm) of the lung with metastasis to
      mediastinal lymph nodes.

PMID- 18078085
TI  - [Brugada syndrome].
AB  - Brugada syndrome is characterized by the right bundle branch block type
      electrocardiogram (ECG) with ST-segment elevation and ventricular fibrillation
      (Vf) attack in patients without obvious heart disease. Its background is
      considered to be the genetic Na channelopathy. The coved type is a typical
      morphology and is classified into type 1 in the European Society of Cardiology
      (ESC). In general, the coved type and the saddel-back type (type 2, 3 in the ESC)
      are interchangeable, and the latter is more frequently detected clinically. For
      diagnosis of the Brugada syndrome, confirmation of the type 1 morphology is
      needed. Administration of Na channel blocker, pilsicainide, is a sensitive test
      for confirmation of the type 1. When the type 1 has one of 7 items recommended by
      the ESC, the patient is diagnosed with Brugada syndrome. ECG finding alone is
      classified into patient with Brugada type ECG. As there is no reliable medical
      treatment, implantation of a cardioverter defibrillator is indicated in patients
      with Brugada syndrome, and observation alone in those with Brugada type ECG.

PMID- 18078086
TI  - [In these days molecule target drug in advanced non-small cell lung cancer].
AB  - Conventionally advanced-non-small cell lung cancer have been treatment platinum
      and 90S new drug (paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan).
      However survival benefit is several months and treatment outcome have arrives at
      plateau. One molecule target drug have been attract attention. In this chapter
      mainly on gefitinib that refer that have been to data that clinical trial and
      EGFR gene mutation and resistance to EGFR-TKI. EGFR mutation with an initial
      dramatic response acquired resistance to the EGFR-TKI. Until the present that
      stracture have been participate T790M for acquired resistance and amplification
      of the MET gene is another mechanism of acquired resistance to EGFR-TKI.

PMID- 18078087
TI  - [An infant case of a rupture of chordae tendineae; report of a case].
AB  - We report a case of 5-month-old boy with severe mitral regurgitation due to a
      rupture of chordae tendinae. Cardiac echography showed a prolapse of the anterior
      cusp of the mitral valve. He was progressively deteriorated despite maximal
      medical treatment, and a surgical intervention was performed 15 hours after the
      onset. The operative finding was a rupture of chordae tendinae attached to the
      anterior cusp of the mitral valve. The infant underwent mitral valve plasty using
      artificial chordae together with partial annulo-plasty. A rupture of chordae
      tendineae is extremely rare in infants, and its cause is yet unknown. Chordal
      reconstruction is feasible even at this early stage of life, although the long
      term follow-up is mandatory.

PMID- 18078088
TI  - [The Waffle procedure for constrictive epicarditis after direct closure of atrial
      septal defect; report of a case].
AB  - A 20-year-old man was admitted with a diagnosis of constrictive pericarditis 6
      months after direct closure of atrial septal defect (ASD). He complained of
      fatigue and dyspnea. Cardiac echo cardiography, computed tomography (CT),
      magnetic resonance imaging (MRI) and cardiac catheterization suggested
      pericardial and epicardial constriction. During the operation, the thickened
      pericardium was peeled off. Multiple longitudinal and transverse incisions were
      made in the thickened epicardium as reported by waffle. Postoperative hemodynamic
      state was improved. The cardiac index increased from 1.91 to 3.17 l/min/m2. The
      pulmonary capillary wedge pressure (PCWP) decreased from 26 to 14 mmHg, although
      dip and plateau pattern was maintained. The postoperative course was uneventful.

PMID- 18078089
TI  - [Preoperative pulseless electrical activity of acute type A aortic dissection;
      report of a case].
AB  - An 80-year-old man with acute type A aortic dissection, who was preoperatively
      observed in the intensive care unit, suddenly became unresponsive. The patient
      was immediately intubated, but a pulse check was delayed because the cardiac
      monitor seemingly showed a normal sinus rhythm. Bedside echocardiography, while
      continuing cardiopulmonary resuscitation, revealed massive pericardial effusion.
      It indicated the patient's cardiac arrest was pulseless electrical activity (PEA)
      due to cardiac tamponade. After pericardiocentesis, a perfusion rhythm was
      restored with palpable distal pulse. He successfully underwent a prosthetic graft
      replacement of the ascending aorta and was discharged after physical
      rehabilitation.

PMID- 18078090
TI  - [Intrapulmonary sequestration operated by video-assisted thoracoscopic surgery
      lobectomy; report of a case].
AB  - Pulmonary sequestration is a rare malformation of the respiratory tract. We here
      report an adult case of intralobar pulmonary sequestration with aberrant artery
      of the right lower lobe. A 20-year-old man admitted to our hospital with a chest
      discomfort. Chest computed tomography (CT), angiography, and scintigraphy showed
      abnormal findings of the right lower lobe with an aberrant artery. Under the
      diagnosis of pulmonary sequestration, video-assisted thoracoscopic surgery (VATS)
      lobectomy was performed. VATS is useful for the operation of pulmonary
      sequestration.

PMID- 18078091
TI  - [Mycobacterium avium complex (MAC) infection needed differential diagnosis of the
      recurrence after surgery for double lung cancer; report of a case].
AB  - A 62-year-old woman had undergone video-assisted thoracic surgery (VATS) -right
      upper lobectomy and right S8 segmentectomy for double lung cancers (papillary
      adenocarcinoma and bronchioloalveoler carcinoma, stage IA). Four years later,
      chest computed tomography (CT) showed abnormal shadow, 20 mm in size, along the
      staple-suture line. The 3 months later, new lesion, 15 mm in size, was observed
      in right lower lobe. CT-guided biopsy revealed no malignancy. The patient
      underwent partial resection of the right lower lobe and tumorectomy. The tumor
      was solid and cystic mass. Histopathologically, the tumor was granuloma infected
      by Mycobacterium avium. The patient was discharged on 17th postoperative day, and
      doing well without new lesion for 9 months postoperatively.

PMID- 18078092
TI  - [Thymic carcinoid with lymph node metastases; report of a case].
AB  - A 71-year-old man was admitted to our hospital because of the detection of an
      anterior mediastinal tumor. Fluorodeoxyglucose-positron emission tomography (FDG
      PET) showed abnormal accumulations in the tumor and the hilar and the supra
      clavicular lymph nodes. Preoperatively, percutaneous needle biopsy of the tumor
      revealed thymic carcinoid. Tumor resection and thymectomy with mediastinal and
      supra-clavicular lymph nodes dissection were performed because of suspecting
      metastasis to the lymph nodes from FDG-PET. Postoperative pathological diagnosis
      revealed atypical carcinoid and metastases to the mediastinal and supra
      clavicular lymph nodes. In our case, FDG-PET was useful in detecting the thymic
      carcinoid and lymph node metastasis. It is desirable to perform clinical research
      by many facilities for the assessment of FDG-PET as a diagnostic tool and
      postoperative chemo-radiation therapy for thymic carcinoid.

PMID- 18078093
TI  - [Colopleural fistula caused by recurrence of gastric cancer; report of a case].
AB  - Perforation of colon into the pleural space without diaphragmatic hernia is
      extremely rare. This report illustrates a case of pneumo-pyothorax caused by
      perforation of metastatic tumor of the transverse colon of a 67-year-old woman
      with a history of total gastrectomy and splenectomy for advanced gastric
      carcinoma 4 years before. The patient was admitted to our hospital presenting
      with fever and dyspnea, which subsided after a thoracic drainage. Cultures of
      drained effusion revealed Escherichia coli, Klebsiella and Bacteroides. An
      emergent laparotomy for treatment of mechanical ileus 2 weeks after her admission
      disclosed a tumor obstructing the splenic flexure of the transverse colon, and a
      double-barreled colostomy was made. Pathologic examination of the tumors obtained
      from colon, mesocolon and the parietal peritoneum revealed poorly differentiated
      adenocarcinoma that was the same as her primary gastric cancer.

PMID- 18078094
TI  - [Preoperative evaluation and anesthetic management of a patient with Brugada
      syndrome-like ECG].
AB  - Brugada syndrome has been known as one of the causes of sudden death due to
      ventricular fibrillation. We experienced anesthetic management of seven patients
      with ECG showing Brugada syndrome before surgery, even though they had no
      symptoms nor family history. All of them showed no problems through-out the
      operation. Such patients are often untreated, but they have the risks of cardiac
      accidents such as ventricular fibrillation or sudden death. For preoperative
      evaluation of patients with Brugada syndrome-like ECG, it is important to ask
      them their experience of syncope and family history. Ultrasonic cardiography and
      Holter ECG recording should be done. External defibrillator should be prepared
      and parasympathetic dominant condition must be avoided during the anesthetic
      management.

PMID- 18078095
TI  - [Anesthesia management for laparoscopic prostatectomy and open prostatectomy].
AB  - BACKGROUND: For anesthetic management of traditional open prostatectomy,
      preparation for hemorrhage is necessary. However, it has been considered that the
      amount of bleeding under laparoscopic prostatectomy is less than that of
      traditional open surgery. METHODS: The amount of bleeding and autologous blood
      preparation, fluid balance, and anesthetic management were investigated in
      patients who had undergone laparoscopic or open prostatectomy at the Nippon
      Medical School Hospital between June, 2004 and November, 2005, retrospectively.
      The difference of these aspects between the two surgical method groups was
      evaluated. RESULTS: Thirty-two patients underwent prostatectomy in the
      investigation period. In these patients, 4 patients were excluded due to
      incomplete anesthesia record or change of surgical method. The amount of
      bleeding, and both amount of autologous blood preparation and transfusion in the
      laparoscopic surgery were less than those in the open surgery. There were no
      significant differences in the fluid balance and amount of urine output between
      the two groups. CONCLUSIONS: We conclude that preparation of autologous blood
      transfusion is necessary for the traditional open prostatectomy, but not for the
      laparoscopic prostatectomy.

PMID- 18078096
TI  - [Use of AirWay Scope for tracheal intubation in bright sunlight].
AB  - BACKGROUND: The AirWay Scope (AWS), which is equipped with a wide-angle LCD
      monitor, has been developed to achieve accurate and safe tracheal intubation
      under various conditions, including emergency settings. However, since bright
      sunlight degrades the image quality of LCDs, we investigated its usefulness
      outdoors in bright sunlight. METHODS: A single anesthesiologist intubated a
      mannequin with an AWS and conventional direct laryngoscope indoors and in
      sunlight outdoors, using 6 trials for each condition. Success rate, Cormack
      grade, and intubation time from device insertion to removal were recorded.
      RESULTS: Indoors, all tracheal intubations with both devices achieved Cormack
      grade 1 and were successful. Outdoors, all the laryngoscopes achieved Cormack
      grade 1 and intubation was successful, whereas intubation with the AWS was
      successful in 3 trials, while 2 esophageal intubations and 1 failure also
      occurred. In addition, sunlight deteriorated the image quality of the LCD and
      Cormack grade could not be determined. The intubation times for the AWS and
      laryngoscope indoors were 8.7+/-1.8 and 17.0+/-6.5 sec, and outdoors were 18.7+/
      9.0 and 21.3+/-4.9 sec, respectively. CONCLUSIONS: Our findings indicate that
      successful tracheal intubation with an AWS is difficult to achieve in bright
      sunlight.

PMID- 18078097
TI  - [Right bronchial intubation using a left-sided double-lumen tube in a patient
      with situs inversus].
AB  - A 74-year-old man was scheduled for resection of a pulmonary tumor in the left
      upper lobe. He had asymptomatic complete situs inversus, and therefore his left
      lung had three lobes whereas his right lung had two. Since the tumor had been
      growing through the left upper bronchus into the left main bronchus, it seemed
      that the use of a bronchial blocker in the left bronchus should be avoided. A 37
      Fr left-sided double-lumen tube was rotated in the opposite direction (clockwise)
      and advanced easily into the right (anatomically left) main bronchus under
      fiberoptic guidance. One lung ventilation during the operation was performed
      successfully and there was no postoperative airway complication. Several ways of
      achieving one lung ventilation in patients with situs inversus are discussed in
      this report. The use of a bronchial blocker should be considered first-choice,
      but sometimes its use is inappropriate as in this case. Commercially available
      double-lumen tubes are not intended for use in cases of situs inversus. If a
      double-lumen tube is desired, intentional right bronchial insertion of a left
      sided double-lumen tube seems to be an easy and reliable option.

PMID- 18078098
TI  - [Fiberscope-guided tracheal intubation using two different kinds of laryngeal
      mask].
AB  - We experienced two cases of difficult airway management using laryngeal mask
      airway (LMA) in children. LMA Classic (LMA-C) was used for a 4-year-old female
      patient and SOFTSEAL LMA (LMA-S) was used for a 15-year-old female patient. Both
      patients were successfully intubated by fiberoptic tracheal intubation through
      LMA. We compare these two kinds of LMA in fiberoptic intubation method. Because
      the diameter of the shaft is wider than LMA-C, LMA-S could pass through much
      larger size endotracheal tube (ETT). 4.0 mm ETT could pass through LMA #1 and
      #1.5 in both LMAs. 5.0 mm ETT could pass through LMA-S #2, but only 4.5 mm ETT
      could pass through LMA-C #2. In #2.5, LMA-S and LMA-C could be passed by 6.0 mm
      ETT and 5.5 mm ETT respectively. Also LMA-S and LMA-C #3 could be passed by 7.0
      mm ETT and 6.5 mm ETT respectively. We conclude that SOFTSEAL LMA is more useful
      than LMA Classic for fiberoptic tracheal intubation technique.

PMID- 18078099
TI  - [Case report of anesthetic management for an infant with tricho-hepato-entric
      syndrome].
AB  - Tricho-hepato-entric syndrome is a rare congenital disorder characterized by hair
      anomalies, neonatal hemochromatosis and intractable diarrhea. A three-year-old
      girl with this syndrome received general anesthesia for inguinal hernia repair.
      Anesthesia was induced with nitrous oxide and sevoflurane, and maintained with
      sevoflurane and fentanyl without muscle relaxant. Rectal acetaminophen was
      administered and ilioinguinal block was performed for postoperative analgesia.
      The anesthetic course was uneventful.

PMID- 18078101
TI  - [Effect of aging on preoperative oxidative stress].
AB  - We investigated the effect of aging on preoperative oxidative stress by measuring
      serum hydroperoxide values in 35 patients who underwent elective surgery under
      general anesthesia. A small amount of blood was withdrawn through an intravenous
      catheter and serum hydroperoxide values were measured using the Free Radical
      Analytic System (FRAS4). Aging and oxidative stress are significantly and
      positively correlated (P < 0.001, r = 0.622). Although the reason is unknown,
      oxidative stress increases concomitantly with aging.

PMID- 18078100
TI  - [Postoperative profound hypoglycemia after resection of adrenaline-predominant
      pheochromocytoma].
AB  - A 54-year-old woman was scheduled for resection of pheochromocytoma. Anesthesia
      was maintained with general anesthesia combined with thoracic epidural
      anesthesia. The blood glucose decreased to 30 mg x dl(-1) about four hours after
      the tumor resection, despite intravenous administration of glucose at a rate of
      15 g x hr(-1) with intermittent boluses of 5 g of glucose. The blood glucose
      levels increased over 100 mg x dl(-1) with intravenous administration of 15 g x
      hr(-1) glucose, 6 hours after tumor resection.

PMID- 18078102
TI  - [Cesarean section for case with preoperatively-suspected placenta accrete
      followed by hysterectomy due to uncontrollable massive bleeding].
AB  - A 42-yr-old pregnant woman highly suspicious of the placenta accreta was
      scheduled for cesarean section (c-section) under general anesthesia. She had
      received emergency c-section for the placenta previa at 36 years of age and three
      episodes of intrauterine curettage for spontaneous abortion. While the
      possibility of placenta accreta was pointed out and the risks accompanying with
      it were explained at the 7th week of pregnancy, she insisted on having a baby. C
      section was intended at around the 30th week of pregnancy and 1,200 ml of
      autologus blood was stored for the predictable massive bleeding. Bilateral
      embolization of the internal iliac artery was also planned. The baby was
      delivered uneventfully. However, the adherence of the placenta was so tight that
      the placenta could not be separated from the uterine wall. The arterial
      embolization immediately after the delivery did not work as effectively as to
      control massive bleeding. It took about 1 hour to control the massive bleeding of
      up to 9000 ml by difficult hysterectomy. Since we had prepared for such a
      situation, we could well catch up with the massive bleeding. The mother and baby
      were discharged well from the hospital 29th day after the c-section.

PMID- 18078103
TI  - [Accidental epidural administration of vecuronium].
AB  - We report a case of accidental epidural injection of vecuronium during
      cholecystectomy in a 55-year-old man (63 kg, 158 cm). Following 3 ml of lidocaine
      1% as an epidural test dose, inadvertent epidural (T7-8) injection of vecuronium
      4.25 mg instead of ropivacaine occurred. After immediate removal of the syringe
      containing vecuronium, 10 ml of ropivacaine 0.375% was injected epidurally.
      Intubation was performed under propofol infusion using a target-controlled
      infusion system with intravenous vecuronium 10 mg. There was a 3 min interval
      between inadvertent epidural and intravenous injection of vecuronium. Anesthesia
      was maintained with propofol infusion (2.6-3.0 microg x ml(-1)) titrated to
      maintain bispectral index between 35-55 and buprenorphine 0.16 mg with 40% oxygen
      in air. T1 response in the train-of-four (TOF) appeared 87 min after epidural
      vecuronium injection. Ten minutes later, additional vecuronium 0.5mg was required
      due to bucking. Seven minutes after that, T1 in the TOF reappeared and the
      operation was finished. Twenty-three minutes after the additional vecuronium, 4
      responses in the TOF were obtained. Following reversal with atropine 1.0 mg and
      neostigmine 2.0 mg, the patient was able to sustain head lift and handgrip, and
      to protrude the tongue fully awake. The patient was extubated 124 min after
      epidural vecuronium injection. There was no memory of back pain during epidural
      vecuronium injection. There was no postoperative respiratory insufficiency or
      neurological disorder. We suspect the duration of action of epidural vecuronium
      is approximately twice that of intravenous injection and becomes prolonged with
      higher doses and advanced age.

PMID- 18078104
TI  - [Recent changes in the incidence of life-threatening events in the operating
      room: JSA surveys between 2001 and 2005].
AB  - BACKGROUND: In Japan, the number of medical staff charged with criminal liability
      has been increasing since 2000, and this medico-legal trend seems to be promoting
      topics of medical risk management in government, academic meetings and individual
      hospital. A survey conducted by the Japanese Society of Anesthesiologists (JSA)
      has been widely accepted among JSA-certified training hospitals, and its
      denominator has exceeded one million since 2001. The purpose of this
      investigation is to examine changes in the incidence of life-threatening events
      in the operating theater between 2001 and 2005 based on the data of the surveys.
      METHODS: JSA has conducted annual surveys of life-threatening and neurological
      events in the operating theater by sending and collecting confidential
      questionnaires to all JSA certified training hospitals. Cases of life-threatening
      events between 2001 and 2005 were analyzed. The recovery rates ranged from 76.2%
      (in 2005) to 91.6% (in 2002), and the annual patient numbers available for
      analysis ranged from 1,051,245 (in 2005) to 1,367,790 (in 2003) during the study
      period. The patients with ASA PS 1 or 2 were classified as having good physical
      status, and those with ASA PS 3 or 4 were classified as having poor physical
      status. Because mortalities (within 7 postoperative days) are more common in
      patients with poor physical status, in emergency patients, in neonate, in the
      elderly, and in patients undergoing cardiovascular surgery, the mortality rate in
      these patients were investigated. The recovery rate from cardiac arrest without
      any sequelae was also investigated. The causes of events were classified as
      follows: totally attributable to anesthetic management (AM), mainly to
      intraoperative pathological events (IP), to preoperative co-morbidity (PC), and
      to surgical management (SM). IP consists of pulmonary thromboembolism, acute
      coronary syndrome, anaphylaxis and so on. The incidence of cardiac arrest and
      mortality are indicated per 10,000 patients. Odds ratio and 95% confidential
      interval are shown in comparison with the incidence in 2001 to that in 2005.
      RESULTS: The incidences of cardiac arrest were 6.12 in 2001, 5.79 in 2002, 5.89
      in 2003, 5.09 in 2004, and 4.24/10,000 patients in 2005, respectively (odds ratio
      0.69; CI 0.62-0.78). The incidences of death within 7 postoperative days due to
      intraoperative life-threatening events were 6.41 in 2001, 6.31 in 2002, 6.61 in
      2003, 5.88 in 2004, and 4.91/10,000 patients in 2005, respectively (OR 0.77; CI
      0.69-0.85). The incidences of death in patients with poor physical status (from
      35.48 to 26.87/10,000 patients; OR 0.76; CI 0.66-0.86), in emergency patients
      (from 37.25 to 30.55/10,000 patients; OR 0.82; CI 0.72-0.93), in neonates (from
      70.09 to 31.70/10,000 patients; OR 0.45; CI 0.22-0.91) and in the elderly (from
      11.03 to 8.75/10,000 patients; OR 0.79; CI 0.68 to 0.92) decreased. The incidence
      of death in patients undergoing cardiovascular surgery ranged between 61.22 and
      76.88/10,000 patients, and has not shown any significant decline. The incidences
      of death due to IP (from 0.65 to 0.42/10,000 patients; OR 0.64; CI 0.44-0.92), PC
      (from 4.14 to 3.30/10,000 patients; OR 0.80; CI 0.70-0.91) and SM (from 1.49 to
      1.02/10,000 patients; OR 0.68; CI 0.54-0.87) decreased. However, the incidence of
      death due to AM ranged between 0.07 and 0.11/10,000 patients, and has not shown
      any significant decline partly because of the small number of deaths from this
      cause. Although recent trends in life-threatening events seemed to be favorable,
      the recovery rate from cardiac arrest decreased from 40.3% in 2001 to 30.7% in
      2005 (OR 0.66; CI 0.51-0.84). CONCLUSIONS: The incidence of life-threatening
      events in the operating room and mortality due to these events seemed to have
      decreased during the recent five years, probably because of progress in risk
      management in JSA-certified training hospitals. The decrease was obvious in the
      recent two years. However, the results should be interpreted cautiously, because
      the response rate to the questionnaire in 2005 was the lowest. To confirm this
      trend, we should perform a follow-up survey for 2006 and continue the survey. The
      reasons for the deterioration in the recovery rate from cardiac arrest should
      also be examined.

PMID- 18078105
TI  - [Predictive factors for treatment incompletion in elderly patients with newly
      diagnosed pulmonary tuberculosis].
AB  - BACKGROUND: To identify predictive factors of treatment incompletion in elderly
      patients with newly diagnosed pulmonary tuberculosis. MATERIALS AND METHODS: In
      elderly patients of more than 65-years old and with newly diagnosed pulmonary
      tuberculosis, a retrospective study was conducted. A total of 88 patients were
      admitted in International Medical Center of Japan with pulmonary tuberculosis
      between June 2000 and February 2002. The relationships between several clinical
      parameters, including patients' performance status (PS) scale proposed by the
      Eastern Cooperative Oncology Group, laboratory data, or, radiological findings on
      admission and treatment incomeletion were assessed by univariate and multivariate
      logistic regression analyses. RESULTS: Ten patients could not complete their
      treatment; including nine patients who died during hospitalization and one who
      refused tuberculosis treatment. Preliminary analysis indicated that the treatment
      incompletion was related with twelve factors including PS. On univariate
      analyses, 9 factors were associated with incomplete treatment. The best model was
      built up by using 5 independent factors, that is, diabetes mellitus, PS,
      hypoxemia, duration of sleep, drug resistant strain. On multivariate analysis,
      only the PS was significantly related to treatment incompletion in elderly
      patients with pulmonary tuberculosis (odds ratio: 0.41, 95% confidence interval:
      0.17-0.98, p=0.04). CONCLUSION: High PS showed a strong association with
      treatment incompletion in elderly patients with pulmonary tuberculosis. The PS is
      considered to be a useful clinical indicator.

PMID- 18078106
TI  - [Severe adverse reactions after vaccination with Japanese BCG vaccine: a review].
AB  - Japanese BCG vaccine has been admitted by the quality control of World Health
      Organization (WHO) as the safest BCG vaccine in the world. Even though, BCG, as a
      live bacterial vaccine, inevitably causes dissemination beyond vaccination site
      and regional lymph-nodes to various part of the body under certain special
      conditions. We tried to review the clinical features and immunological status of
      the cases in which "severe" adverse reactions had developed after vaccination
      with Japanese freeze-dried BCG vaccine prepared from BCG substrain Tokyo.
      "Severe" adverse reaction was arbitrarily defined as the adverse reactions of
      clinical significance developed beyond vaccination site and regional ipsilateral
      axillary lymph-nodes. By the extensive search of the literatures, 39 cases were
      identified since 1951 when vaccination with freeze-dried BCG vaccine became
      compulsory by the Tuberculosis Prevention Law in Japan. Incidence rate was
      calculated as 0.0182 cases per 100,000 vaccinations. Clinical manifestations of
      bone and joint were reported in 27 cases (multiple sites: 15 cases, single site:
      12 cases), abnormalities in chest X-ray in 13 cases, skin manifestations in 17
      cases, diseases in other sites or organs in 8 cases. Most of the cases had
      lesions in multiple organs. Among these 39 cases, 13 had been diagnosed to have
      some types of primary immunodeficiency (5 cases: chronic granulomatous disease
      (CGD); 4 cases: severe combined immunodeficiency (SCID); 4 cases: IFN-gamma
      receptor 1 deficiency). Further, unidentified defects in cellular immunity were
      reported in other 6 cases. Death was reported in 6 cases, but in two cases the
      causes of death were the infections due to different pathogens, namely, pulmonary
      abscess due to Staphylococcus sp. and bacteremia due to Pseudomonas aeruginosa,
      respectively, and in only one case death was evidenced as due to disseminated BCG
      infection by autopsy. All of 6 death cases had some type of immunodeficiency.
      Apart from fatal cases, outcome of "severe" adverse events were generally
      favorable and they were successfully treated by anti-tuberculosis therapy with or
      without surgical treatment for bone and joint lesions. Because the risk of
      "severe" adverse reactions is high among those of primary immunodeficiency, so it
      is advisable to avoid BCG vaccination during the first three months after birth
      when the detection of immunodeficiency is practically impossible.

PMID- 18078107
TI  - [Case of laboratory cross-contamination of Mycobacterium tuberculosis in the
      broth-based culture system].
AB  - We experienced a case of laboratory cross-contamination of Mycobacterium
      tuberculosis on the broth based culture system. These false-positive cultures
      were confirmed by analysis of DNA fingerprinting, RFLP method, which showed the
      same pattern in three specimens with that of the first manipulated specimen in
      our laboratory on that day, out of 7 specimens examed. We found possible several
      process causing cross-contamination where mixture of the foreign body could occur
      in buffer or NALC-NaOH. False-positive cultures for Mycobacterium tuberculosis
      may lead to unnecessary, potentially toxic, costly treatment, and changing the
      treatment strategy. So we must critically interpret a single positive culture,
      especially by liquid media.

PMID- 18078108
TI  - [Case of multi-drug resistant pulmonary tuberculosis with bilateral cavitary
      lesions successfully treated by surgical treatment].
AB  - A case was 38 years old male. He was pointed out abnormal shadow on chest X-ray
      and complained respiratory infection symptoms. He had not past history of
      tuberculosis. He was diagnosed as multi-drug resistant tuberculosis (MDR-TB) in a
      certain hospital and was referred to our hospital to undergo treatment. His drug
      sensitivity test by Ogawa medium was resistant to all anti-tuberculosis drugs
      except for kanamycin (KM) and enviomycin (EVM). His chest X-ray revealed large
      cavities in the right upper field and infiltrations in the right lower field and
      small cavitary lesions in the left lower field. The right pneumonectomy was done
      because he took anti-tuberculosis drugs but his sputum examinations continued to
      be smear and culture positive without improvement of the lesions. After the
      surgical treatment (right pneumonectomy), he continued anti-tuberculosis drugs
      therapy and the chest X-ray improved including the collapse of left lower
      cavitary lesions. This case was a difficult case to treat because of bilateral
      cavitary lesions. However he was successfully treated by the surgical treatment.

PMID- 18078109
TI  - [Investigation on the changes in the hospitalization period after the induction
      of new discharge criteria for pulmonary tuberculosis--utility of assessment sheet
      for using clinical path].
AB  - PURPOSE AND METHODS: The new discharge criteria devised by the National Hospital
      Organization have three patterns (A, B and other). It was predicted that the
      hospitalization period would be markedly shortened by the pattern A. In order to
      judge whether these patterns were adequately applied, we used an assessment
      sheet. We investigated the adoption rate of the pattern A and the changes in the
      hospitalization period after its induction. RESULTS: There was a low adoption
      rate for the pattern A; namely 18%, and the main reasons for not following it
      were severity illness and the presence of complications. Hospitalization for less
      than 4 weeks was seen in 25%, while it was over 8 weeks in 42%. The average
      period of hospitalization was shortened by 20 days and the average number of
      patients per day also decreased. CONCLUSION: Interpretation of discharge criteria
      is standardized by using the assessment sheet, allowing us to perform smooth
      induction of a clinical path and guide patients along it. Shortening of
      hospitalization raises patient turnover and allows more rational management of
      pulmonary tuberculosis. These results could help to refine the clinical path in
      the future.

PMID- 18078110
TI  - [Diagnosis and treatment of tuberculosis or Mycobacterium avium-intracellulare
      complex infection in HIV-infected patients].
AB  - The clinical features of tuberculosis vary according to its CD4 count. With CD4
      count >350/microL pulmonary lesions are "typical" (upper lobe infiltrates +/-
      cavitation). With CD4 count< 50/microL extrapulmonary TB is more common, and
      chest X-rays show lower and middle lobe and miliary infiltrates, usually without
      cavitation. The treatment of tuberculosis in HIV-infected patients should follow
      the same principles for persons without HIV infection. Presence of active
      tuberculosis requires immediate initiation of anti-tbc therapy. The delay of
      antiretroviral therapy for 4-8 weeks after initiation of tuberculosis treatment
      is recommended. MAC is a relatively common cause of disseminated infection
      without pulmonary involvement in patients with AIDS. Preferred regimens contain
      clarithromycin and EB, and in case of high MAC load or absence of effective
      antiretroviral therapy rifabutin may be considered as a third drug. Start
      antiretroviral therapy simultaneously or within 1-2 weeks. In Japan, an
      increasing number of HIV infections are reported year after year. So HIV
      infection should be included in possible diagnosis for atypical Tbc or
      disseminated MAC infection.

PMID- 18078111
TI  - [Surgical treatment of mycobacteriosis].
AB  - The pulmonary resection plays an important role in the management of
      tuberculosis, especially MDRTB, or non-tuberculous mycobacteriosis. For the
      satisfactory outcome, pre- and postoperative chemotherapy is mandatory. On the
      same time, resected specimens should be examined bacteriologically to evaluate
      preoperative chemotherapy. Acute mycobacterial empyema occurs frequently by the
      perforation of cavitary lesions, especially with pulmonary NTM. The outcome of
      such acute and destructive diseases is poor in the case of old age over 70y/o.
      But without surgical intervention, such difficult condition becomes more
      miserable. Although mycobacterial mediastinal lymphoadenitis, or osteoarthritis
      are rare tuberculosis-related disease in Japan, we should keep in mind such rare
      diseases in ordinary practice.

PMID- 18078112
TI  - [Tuberculosis control in urban areas].
AB  - Directly Observed Treatment, Short Course (DOTS) in Japan was initiated and is
      now established for homeless TB patients in urban areas. The experience of this
      DOTS is assisting the development of DOTS in Japan. However, TB incidence and
      problems are now concentrated in urban areas. What makes tuberculosis control in
      urban areas difficult? How can we overcome these problems? In this symposium we
      reviewed TB control activities and discussed the issues highlighted by four
      presenters.

PMID- 18078113
TI  - [Clone of Staphylococcus aureus phage type 187 isolated from people].
AB  - The aim of this study was to examine whether Staphylococcus aureus of phage type
      187 are genetically homogenous with the use of digestion of chromosomal DNA with
      SmaI and separation of the DNA by pulsed-field gel electrophoresis (PFGE).
      Sixteen S. aureus phage type 187 were isolated from the hospital patients (12)
      and the healthy carriers (4) in twelve medical centres in Poland during 1991 and
      2005. The PFGE typing proved that the phage type 187 isolates have the same PFGE
      type (except for one) and constitute one clone.

PMID- 18078114
TI  - [Occurrence of selected enterotoxins and toxic shock syndrome toxin genes among
      sensitive and resistant to methicillin Staphylococcus aureus isolated from
      clinical samples].
AB  - The aim of study was to estimate frequency of occurrence of enterotoxins (sea
      sed) and TSST-1 (tst) genes. One hundred seven methicillin-sensitive and one
      hundred three methicillin-resistant strains of S. aureus isolated from hospital
      patients in 21 medical centers, in majority from the region of Gdansk were
      examined. The presence of selected toxins genes was detected by multiplex PCR.
      The results showed that almost 80% of MRSA strains were positive for sea gene, in
      contrast to MSSA (17,8%). Both MSSA and MRSA strains were rarely positive for the
      presence of other enterotoxins genes seb, sec, sed (less than 10%) and a tst gene
      was detected in about 15% of them. No correlation between presence of the
      particular genes and clinical samples was observed.

PMID- 18078115
TI  - [Prevalence of virulece-associated genes of Enterococcus faecalis clinical
      strains isolated from patients and volunteers].
AB  - Enterococcus faecalis is an important cause of serious hospitals infections.
      Several E. faecalis putative virulence determinants have been identified. The aim
      of our study was to determine the prevalence of virulence factors among 180
      strains of E. faecalis isolated from humans from different clinical sources in
      Poland. Tested strains were investigated for the presence of cylA, cylB, cylM,
      gelE, asal, esp, efaA and ace by using PCR method. Among all strains ace and efaA
      were most often detected. However, in opposite to strains obtained from faeces of
      volunteers, most of clinical strains carried esp (64,4% vs. 28,9%) and cylA
      (44,4% vs. 20%), cylB (41,5% vs. 20%), cylM (45,2% vs. 20%), respectively. Twenty
      different virulotype were represented by tested strains. Presence of all tested
      virulence determinants were the most frequently observed among clinical strains.
      There was no significant association between virulence factors and clinical
      source of isolation.

PMID- 18078116
TI  - [Non-specific adherence of Enterococcus faecalis strains isolated from healthy
      voluntaries and infection of urinary tract].
AB  - Enterococcus faecalis is a component of human and animal gastrointestinal
      microflora. However, the adhesion is considered to be the key step in the
      pathogenesis of enterococcal infections and the first step of biofilm formation.
      We aimed to compare and evaluate adherence of strains considered to be commensal
      flora (isolated from healthy volunteers) and strains isolated as a pathogen from
      medical samples in Gdansk Region The additional aim of this study was to analyze
      influence of subinhibitory concentration of gentamycin and cAD1 pheromone.
      Comparison involved 20 strains isolated from healthy voluntaries, 23 strains
      isolated as etiological agent of urinary tract infection and 16 HLAR strains from
      other infections. Adherence ability was tasted by turbidymetric method at 550 nm,
      as o reduction of bacterial inoculum after incubation with hydroksyapatite.
      Results showed significant difference between commensal and virulent strains as
      well as between none-inducted and inducted by pheromone. In contrast there was no
      difference between inducted and non-inducted virulent strains as well as between
      inducted virulent and inducted not virulent strains. The result shows ability to
      differentiate this group by non-specific adherence.

PMID- 18078117
TI  - [Estimation of the contribution of the small plasmids in creation of ESBL
      phenotype among clinical and ambulatory isolates of the Enterobacteriaceae].
AB  - Here we demonstrated that the small plasmids below (20 kpb) are responsible for
      maintaining and dissemination of ESBL phenotype among the different species of
      Enterobacteriaceae family. The similarity of plazmid profiles isolated from E.
      coli and Klebsiella pneumoniae and K. oxytoca suggests possibility of the
      exchange of these plazmids between two mentioned species of bacteria.

PMID- 18078118
TI  - [Imipenem resistance in Gram-negative rods and its consumption between 1999 and
      2005].
AB  - Multidrug resistant Gram-negative rods are increasingly isolated from clinical
      specimens, especially from hospitalized patients. The aim of this study was to
      evaluate the prevalence of imipenem resistant strains of Gram-negative rods
      isolated in dr. A. Jurasz University Hospital in Bydgoszcz between 1999 and 2005
      and imipenem consumption in this period. Out of 109614 isolated microorganisms,
      Gram-negative rods were 28,5%, 637 (2,0%) of strains were resistant to imipenem.
      These strains were isolated mostly from patients hospitalized in intensive care
      and rehabilitation clinics. Among imipenem-resistant strains Pseudomonas
      aeruginosa prevailed (88,9%). P. aeruginosa strains were sensitive to colistin,
      45,5% of them to aztreonam and 44,0% to ceftazidime. The imipenem consumption in
      the appropriate years included in this study was: 805,00; 1201,25; 940,00;
      1390,00; 1660,00; 1341,25; 1841,25 DDD respectively, and was strictly connected
      with increasing imipenem-resistant Gram-negative rods isolation.

PMID- 18078119
TI  - [An immunoblotting as a method for the diagnosis of typhoid fever].
AB  - The patients' sera had been referred to the National Salmonella Centre for
      routine Widal serology. Sera were predominately from patients suspected of having
      been infected with Salmonella Typhi, but also included one serum from patient
      with typhoid fever who was culture positive for Salmonella Typhi. The
      immunoblotting procedure using Salmonella Typhi somatic (O=9,12 LPS) and
      flagellar (H=d) antigens was used for preliminary testing of selected patients
      sera previously evaluated by Widal agglutination assay as containing different
      levels of antibodies against O and/or H antigens of Salmonella Typhi. Following
      Chart et al., immunoblotting reactions were graded between 0 and 3, with 0
      indicating an absence of antibody binding, and 3 where antibody binding was
      readily observed. Sera giving reaction of 2 or 3 were considered to be antibody
      positive for this study. Positive immunoblotting reaction to O=9,12 LPS antigen
      was obtained only with the serum of patient with typhoid fever. Presence of
      specific anti-LPS antibodies was also observed in two other patients' sera
      diluted 1:50, and in case of one of them also in dilution 1:200, but intensity of
      antigen-antibody reaction was under positive result criterion. The most other
      sera positive to O=9,12 antigen in law dilutions (1:50, 1:100) by Widal assay,
      showed the traces of non-specific reaction by immunoblotting. Presence of
      positive antigen-antibody reaction was indicated for five sera in dilution 1:50
      when tested with the >55 kDa H=d flagellar protein subunit, including the serum
      of patient with typhoid fever. Only in this serum the high level of specific
      antibodies was detected also in dilution 1:200, what was not observed in case of
      the other four, which appeared negative. All the other sera were shown not to
      contain antibodies to flagella antigen. Although the presented results are
      preliminary and additional study of more sera of people infected with Salmonella
      Typhi is needed, it can be concluded after Chart et al., that an immunoblotting
      procedure incorporating O=9,12 LPS and flagellar H=d antigens is a useful method
      for providing serological evidence of infection with Salmonella Typhi. In our
      opinion it can serve as a rapid test for the diagnosis of typhoid fever.

PMID- 18078120
TI  - [Production of antibacterial substances by resident corynebacteria isolated from
      human skin].
AB  - Coryneform bacteria, especially lipophilic species, form stable but not dominant
      population on a human skin. This position is probably controlled by secretion of
      bacteriocin-like substances, which act directly on coexisting bacteria. Among 118
      investigated corynebacteria belonging to seven species/taxa and isolated from
      human skin, 90% possessed an ability to produce such substances. The spectrum of
      their activity was restricted to killing gram-positive bacteria, but along with
      corynebacteria it also covered cocci, with Staphylococcus aureus in this group.
      This feature was revealed better on low pH media (pH 5.6) and media with 1.5%
      NaCl for cocci, but on pH 7,4 for corynebacteria.

PMID- 18078121
TI  - [Laboratory diagnosis of Epstein-Barr virus infection].
AB  - Laboratory confirmation of EBV infection requires proper methods and schema of
      investigation adequate to aim of diagnostic procedure. In paper the results of
      routine diagnostic tests of EBV infection performed in Department of Virology NIH
      in 2005-2006 years was included and also, evaluation of usefulness of different
      laboratory methods was done. Based on results of ELISA tests 10,7% routine
      investigated subjects was classified as primary EBV infection, 20,1% was
      seronegative, 7,4% was classified as reactivation of latent infection and
      serological markers in 45,6% subjects pointed past EBV infection. Positive result
      of PCR method was obtain in 11,2% samples subjected of routine laboratory
      investigation. Comparison of specific and non-specific serological methods
      results (ELISA versus tests of heterophile antibodies) showed the high percentage
      of false negative results in children tested by non-specific tests. PCR results
      in serum samples from patients with primary infection (confirmed by serological
      tests) were positive in 15% cases only. Based on analyzed results it could be
      stated that reliable confirmation of infectious mononucleosis, as primary EBV
      infection, is detection of specific IgM antibodies and in case of heterophile
      antibodies tests the possibility of false negative results, mainly in children,
      must be taken into account. The most proper samples for PCR method are whole
      blood, sections of tissue or cells from swabs.

PMID- 18078122
TI  - [Cervical dysplasia and microflora of sexual tract].
AB  - The aim of this study was to evaluate microflora of the vaginal part of the
      cervix uteri (including high-oncogenic HPV types and C. trachomatis) in women
      with ASCUS, LSIL comparing with women with normal cytology. The results
      demonstrated that infections with high-oncogenic HPV types and C. trachomatis
      don't reduce significantly Lactobacillus spp.

PMID- 18078123
TI  - [Effect of bone marrow mesenchymal stem cells on immunoregulation in H-2
      haploidentical bone marrow transplantation mice].
AB  - OBJECTIVE: To explore immunoregulatory mechanism of mesenchymal stem cells (MSCs)
      in H-2 haploidentical bone marrow cells transplantation mice. METHODS: BALB/c
      female mice irradiated with 8Gy 60Co gamma-rays were divided into two groups:
      MSCs group, infused cm-DiI labeled MSCs from female CB6F1 mice and monocytes from
      the bone marrow and spleen of male CB6F1; Control group, only infused monocytes
      from the bone marrow and spleen of male CB6F1. T-lymphocyte subpopulation of
      peripheral blood cells, T and B cells proliferation stimulated by ConA and LPS,
      mixed lymphocyte reaction between donor and recipient and third part, the sry
      gene chimerism of bone marrow, spleen and thymus of the recipient, the
      distribution of MSCs in the recipient, the incidence rate of GVHD and survival
      were observed. RESULTS: The CD3 at +90 d the percent of CD3+ CD4+ cells, and
      CD4/CD8 at +30 d in the MSCs group were higher than that in control post
      transplantation, respectively (P < 0.05). The proliferation activity of B cells
      recovered more rapidly and that of T cells recovered comparably in MSCs group as
      compared with that in control group. The result of MLR between donor and
      recipient was lower in MSCs group than that in the control; and that between
      recipient and the third part had no difference. The sry-gene chimerism of bone
      marrow and spleen of the recipient was higher in MSCs group than in control at
      +30 d. The MSCs mainly distributed in intestine, thymus, bone marrow, liver,
      heart of the recipient after transplantation. The incidence of acute GVHD was
      higher and the survival rate was lower in MSCs group than that in control group
      (P < 0.05). Chronic GVHD occurred in the control group at +90 d, while in the
      MSCs group at +120 d. CONCLUSIONS: MSCs might improve stem cell engraftment,
      promote lymphocyte and humoral immunity recovery, decrease incidence of GVHD and
      increase survival by inducing specific immunologic tolerance and repairing organs
      injuries.

PMID- 18078124
TI  - [Study on the behavior of NK cell KIRs of donor/recipient pairs in HLA matched
      unrelated allo-HSCT].
AB  - OBJECTIVE: To study the biological function of killer cell immunoglobulin-like
      receptor (KIR) and the role of donor inhibitory KIR and recipient genetic
      background in HLA matched unrelated hematopoietic stem cell transplantation
      (HSCT). METHODS: HLA genotype of 51 patients (ALL 18 cases, CML 15 cases, AML 10
      cases and others 8 cases) and their respective matched unrelated donors from
      Database of China Marrow Registration was determined by polymerase chain reaction
      sequence oligonucleotide probes (PCR-SSOP) and sequence specific primers (PCR
      SSP). The KIR genotype was determined by PCR-SSP. RESULTS: All the patients and
      the donors expressed KIR2DL1, KIR2DL2/L3, KIR2DL4, KIR3DL2 and KIR3DL3. 96.7%
      individuals expressed KIR3DL1. Among them, 21.57% of KIR was completely
      identical, while 78.43% was not. Of the non-identical KIRs, 25.49% were the
      recipient's KIR genotype containing the donor's ones, and 27.45% was the donor's
      containing the recipient's. 74.62% of donor's KIR2DL1 lacked recipient's C2
      ligand, 5.91% of donor's KIR2DL2/L3 lacked recipient's C1 ligand, 19.74% of
      donor's KIR3DL1 lacked recipient's Bw4 ligand and 54.91% of donor's KIR3DL2
      lacked recipient's A3, A11 ligand. CONCLUSION: KIR genotype and HLA class I
      antigen are inherited independently. KIR2DLI and KIR3DL2 of donors may cause
      alloreactivity of NK cell. The mismatch of KIR/HLA in donor-recipient plays a
      very important role in matched unrelated allo-HSCT. The outcome of HSCT can be
      better predicted by the model of the presence of KIRs on the donor' sNK cells and
      the absence of corresponding KIR ligand in the recipient's HLA.

PMID- 18078125
TI  - [Clinico-pathological analysis of 6 cases of post-transplant lymphoproliferative
      disorders].
AB  - OBJECTIVE: To evaluate clinical and pathological features of post-transplant
      lymphoproliferative disorders (PTLD) and its significance in diagnosis. METHODS:
      Six cases of PTLD were studied by light microscope, immunohistochemistry, in-situ
      hybridization, and gene rearrangement analysis. The clinical and follow-up
      information were also reviewed. RESULTS: Among the 6 cases, 3 with monomorphic
      PTLD were renal transplant recipients, and died 4, 2, and 1 months after
      diagnosis. 2 were liver transplant recipients, 1 of whom with monomorphic PTLD
      died 5 months after diagnosis, the other one was diagnosed as early lesion of
      PTLD and the post-bone marrow transplant case was classified as polymorphic PTLD
      who survived for 12 months after diagnosis of PTLD. EBER 1/2 DNA was demonstrated
      in 4 cases. CONCLUSIONS: PTLD is a lymphoproliferative disease with distinctive
      morphologic and clinical characteristics after organ transplantation. The
      prognosis of PTLD correlates with the pathological subtypes and clinical stage.

PMID- 18078126
TI  - [rhIL-11 accelerates the engraftment of platelets after unrelated cord blood
      transplantation].
AB  - OBJECTIVE: To observe whether rhIL-11 could accelerate the engraftment of
      platelets after unrelated cord blood transplantation (CBT). METHODS: Nine
      patients (3 children and 6 adults) were enrolled in this study. The degree of HLA
      disparity was 0-2 loci. Cord blood was given two units for adults and one unit
      for children. Conditioning regimens were CY/TBI in 1 and BU/CY in 8 cases, both
      with antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis
      consisted of cyclosporine and short-term methotrexate. On day +1, rhIL-11 was
      used at 50 microg x kg(-1) x d(-1) and G-CSF at 5 microg x kg(-1) x d(-1) to
      accelerate hematopoiesis recovery. RESULTS: The median age of the patients was
      22.3 years and the median weight 52.3 kg. Among the 9 patients, 8 (88.9%)
      experienced engraftment. The median time to neutrophil > 0.5 x 10(9)/L was 21.3
      (14-37) days and to platelet > 20 x 10(9)/L was 25 (18-36) days. 42.9% of the
      patients developed grade I aGVHD and 33.3% developed localized chronic GVHD. Six
      patients were alive and disease-free at a median follow-up of 7 months. Infection
      was the primary cause of death. The expected 1-year survival was 77.8%, 2-year
      survival was 52.2%. Five of 8 patients (62.5%) who received IL-11 presented
      leakage syndrome. On prophylaxis with drugs containing Arnebia root extract, all
      patients could tolerate the treatment. CONCLUSION: rhIL-11 maybe helpful for
      accelerating the platelet recovery and reducing aGVHD severity in unrelated CBT.
      The major side effect is leakage syndrome. It is well tolerated on prophylaxis
      with drugs containing Arnebia root.

PMID- 18078127
TI  - [Study on relationship between pretransplantation host thymic recent output
      function and prognosis in HLA-matched sibling hematopoietic stem cell
      transplantation].
AB  - OBJECTIVE: To study the relationship between pretransplantation host thymic
      recent output function and prognosis in HLA-matched sibling bone marrow
      transplantation (MSD-BMT) and determine whether pretransplantation host thymic
      recent output function can act as a marker for predication of prognosis after
      HSCT. METHODS: T-cell receptor excision circle (TREC) in DNA of
      pretransplantation peripheral blood mononuclear cells from 64 patients underwent
      MSD-BMT was detected by real-time quantitative PCR. The content of TREC in 70
      normal donors was detected as well. All clinical data of patients after HSCT were
      collected and studied. Survival rates of patients after HSCT were estimated with
      Log-rank test. Univariate and multivariate analysis of prognostic factors were
      carried out by COX's proportional hazard regression model. RESULTS: The mean
      value of TREC in normal donors was (3351 +/- 3711) copies/10(5) cells. There was
      an inverse correlation between TREC and age in the donor groups. Before
      transplantation, all patients were detected TREC, with a mean TREC number of (180
      +/-332) copies/10(5) cells being significantly lower than that of normal donors.
      The results of univariate analysis showed that the counts of pre-HSCT TREC were
      closely, correlated with long term survival and chronic graft versus host disease
      (cGVHD) (P < 0.05) and with CMV infection (P = 0.084) but not with acute graft
      versus host disease (aGVHD). The results of multivariate analysis showed the same
      thing as that of univariate analysis. CONCLUSION: Pretransplantation host thymic
      recent output function is closely correlated with prognosis in MSD-BMT and can be
      a factor for predicting the outcome of HSCT.

PMID- 18078128
TI  - [Bone marrow microvessel density and vascular endothelial growth factor
      expression in patients with aplastic anemia].
AB  - OBJECTIVE: To study the bone marrow microvessel density (MVD) and vascular
      endothelial growth factor (VEGF) expression and their clinical significance in
      patients with aplastic anemia (AA). METHODS: Bone marrow biopsies in 51 newly
      diagnosed patients with AA were evaluated the MVD and VEGF expression by
      immunostaining with anti-factor VIII related antigen and VEGF monoclonal
      antibodies at regular time points after immunosuppressive therapy (IT). RESULTS:
      The mean bone marrow MVD in AA group was 5.5 +/- 3.5, being significantly lower
      than that in normal control group (8.7 +/- 3.4, P < 0.05). MVDs of SAA and NSAA
      patients were 7.4 +/- 2.9 and 4.3 +/- 3.4, respectively, being significantly
      different (P < 0.01). The VEGF expression in AA group was significantly lower
      than that in control group [(6.7 +/- 8.4)% vs (14.7 +/- 6.1)%, P < 0.01], but
      there was no difference between SAA and NSAA. Bone marrow MVD and VEGF were
      significantly increased after IT in 22 responded AA patients. CONCLUSION: Bone
      marrow MVD and VEGF expression are low in AA patients which may be one of
      pathophysiologic mechanisms of bone marrow failure in AA. Proangiogenic and
      ameliorating microcirculation agents together with IT might accelerate the
      recovery of hematopoiesis in AA patients.

PMID- 18078129
TI  - [Expression of pig7 in acute leukemia and its clinical significance].
AB  - OBJECTIVE: To investigate pig7 expression level in acute leukemia (AL) and its
      clinical significance and explore the possible mechanisms for pig7 silence in
      terms of methylation control. METHODS: Expression levels of pig7 mRNA in bone
      marrow samples from 138 patients with de novo AL and 21 normal controls and in 6
      leukemic cell lines were detected by quantitative real-time reverse transcription
      PCR (RT-PCR). Differentiation induction effect by all-trans retinoic acid (ATRA)
      and concomitant change in pig7 expression were also monitored in NB4 cells.
      Endonuclease analysis was employed to determined the identity of pig7 transcript
      present in AL samples. Methylation specific PCR (MSP) was used to elucidate if
      hypermethylation was responsible for pig7 silence in AL. RESULTS: Compared with
      that in normal control, pig7 expression was markedly decreased (0.62 vs 18.30,
      median, P < 0.01) in AL patients on progression (at diagnosis, relapse or
      refractory). No significant difference was observed between acute myeloid
      leukemia (AML) and acute lymphoblastic leukemia (ALL). AL at diagnosis had a
      higher pig7 level than those with relapsed or refractory disease (1.43 vs 0.16,
      median, P < 0.05). The complete remission (CR) rate after chemotherapy was found
      to be significantly correlated with pig7 expression levels (P < 0.05).
      Differentiated NB4 cells showed an increased level of pig7 expression (from 1.61
      +/- 0.72 to 44.75 +/- 3.93, P < 0.01). Only one form of pig7 transcripts i.e.,
      Small integral membrane protein of late endosome (SIMPLE), was detected in AL
      patients. Hypermethylation of pig7 promoter was identified in K562 and HL-60
      cells, in contrast to non-methylation predominant in U937 cells. CONCLUSION:
      Aberrant down-regulation of pig7 provides novel insights into leukemogenesis and
      therapy response prediction in AL.

PMID- 18078131
TI  - [The expression of beta-catenin and its significance in leukemia cells].
AB  - OBJECTIVE: To investigate the expression of beta-catenin in patients with
      leukemia and explore its significance in leukemias. METHODS: RT-PCR was used to
      detect the expression of beta-catenin in bone marrow mononuclear cells (BMMNCs)
      from patients with leukemia. Immunocytochemistry was in some of patients to
      detect the distribution of beta-catenin at the same time. The clinical
      significance of beta-catenin was analyzed in combination with patients' clinical
      information. RESULTS: Expression of beta-catenin was statistically higher in
      acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) samples than in
      normal donors (P = 0.001 and 0.016 respectively) and chronic phase chronic
      myeloid leukemia (CML) patients (P = 0.001 and P = 0.008 respectively), while
      there was no statistic difference between AML and ALL patients (P = 0.58). In
      addition, beta-catenin expression in chronic phase CML patients was like that in
      normal donors (P = 0.49), but increased significantly in blast crisis and
      accelerated phase. Immunocytochemical analysis revealed that BMMNCs from normal
      donors expressed beta-catenin on the plasma membrane and cytoplasma, while those
      from acute leukemia expressed beta-catenin to varying degrees in the nucleus as
      well. The expression of beta-catenin gene statistically showed the highest level
      in M5 (n = 15) and the lowest level in M3 (n = 18). No clinical features, such
      as, age, initial WBC count, therapy response rate, blast cell numbers or
      cytogenetic risk was found to be correlated with the expression of beta-catenin
      excepting for CD34+ positive rate (P = 0.004) in AML. CONCLUSION: As a key
      mediator of Wnt signal transduction way, overexpression of beta-catenin in
      leukemia cells indicates that it might be aberrantly activated in acute leukemia,
      accelerated or blastic phase of CML.

PMID- 18078130
TI  - [Expression of GATA-1 and GATA-2 in the bone marrow of patients with Monge's
      disease].
AB  - OBJECTIVE: To find out how GATA-1 and GATA-2 behave in the bone marrow of
      patients with Monge's disease. METHODS: The levels of mRNA in mononuclear cells
      (MNC) and proteins of GATA-1 and GATA-2 in the bone marrow of patients with
      Monge's disease and controls were determined by RT-PCR and immune cytolysis
      chemical method. RESULTS: (1) All patients and controls expressed GATA-1 mRNA
      (Monge's disease 1.033 +/- 0.146, Control 0.458 +/- 0.076) and GATA-2 mRNA
      (Monge's disease 0.451 +/- 0.073, Control 0.185 +/- 0.074). All patients
      expressed both GATA-1 (positive cell counts 77.3 +/- 33.3, positive score 135.4
      +/- 75.4) and GATA-2 ( positive cell counts 29.4 +/- 11.4, positive score 48.4 +/
      19.7). All the controls expressed GATA-1 (positive cell counts 18.1 +/- 11.3,
      positive score 24.2 +/- 13.4) while 12 of 20 controls expressed GATA-2 ( positive
      cell counts 5.4 +/- 3.0, positive score 7.3 +/- 4.2). The expression of mRNA and
      proteins of GATA-1 and GATA-2 in Monge's disease were higher than in controls (P
      < 0.01). (2) There was a positive correlation between GATA-1 and Hb (P < 0.01),
      as did between mRNA and proteins of GATA-1 and GATA-2. (3) Both the proteins of
      GATA-1 and GATA-2 located only in the cytoplasm but not the nucleus. CONCLUSIONS:
      Two of inherent genes, GATA-1 and GATA-2 which were expressed at higher levels in
      patients with Monge's disease than in controls might play significant roles in
      the pathogenesis of Monge's disease.

PMID- 18078132
TI  - [Effects of AML1-ETO on transcription activity of p21WAF1/CIP1 gene promoter].
AB  - OBJECTIVE: To observe the effects of AML1-ETO fusion gene on the transcription
      activity of p21WAF1/CIP1 gene. And to explore the enhancement of leukemia
      pathogenesis of AML1-ETO. METHODS: The luciferase reporter plasmids of
      p21WAF1/CIP1 gene promoter were constructed, and co-transfected into CV-1 cells
      with AML1-ETO, AML1b and AML1a expression plasmids. The trans-activity of
      p21WAF1/CIP1 gene promoter was assayed by luminometer. RESULTS: AML1-ETO
      exhibited a distinct inhibition activity of p21WAF1/CIP1 gene promoter with a
      sequence-specificity and dosage-dependent manner. The trans-activity of
      p21WAF1/CIP1 gene promoter decreased to (19 +/- 4)% compared to control group,
      when 1000 ng pCMV5-AML1-ETO plasmid was used. AML1b and AMLla showed less
      inhibition activity. The trans-activity of p21WAF1/CIP1 gene promoter decreased
      to (61 +/- 16)% and (59 +/- 16)% compared to control group, respectively, when
      1000 ng plasmid was used. CONCLUSION: AML1-ETO exhibits more inhibition activity
      of p21WAF1/CIP1 gene promoter than AML1b and AMLla, results from recruiting
      transcription co-repression complex efficiently by ETO. Based on previous
      researches, the effects of exogenous AML1-ETO on p21WAF1/CIP1 gene promote may be
      dependent on the type of cell lines.

PMID- 18078133
TI  - [Abnormal polarization of T lymphocyte induces negative hematopoietic regulation
      in myelodysplastic syndromes].
AB  - OBJECTIVE: To explore polarization of T lymphocyte and its relationship with
      apoptosis of marrow cells in patients with myelodysplastic syndromes (MDS).
      METHODS: Measurements of Th1, Th2, Tc1, Tc2 subsets in bone marrows from 34
      patients with MDS and 13 normal controls were performed by flow cytometry. INF
      gamma and TNF-alpha in marrow serum were determined by ELISA (Enzyme-linked
      immunosorbent assay). Apoptosis index of marrow cells was detected by TUNEL (TdT
      mediated dUTP nick end labeling). Correlations between Th1, Th2, Tc1, Tc2 subsets
      and INF-gamma, TNF-alpha levels as well as apoptosis index were analyzed, and
      relationship between TNF-alpha, INF-gamma levels and apoptosis index was also
      investigated. RESULTS: (1) The percentage of Th1 cells [(10.1 +/- 1.6)%], Tc1
      cells [(24.0 +/- 3.6)%] and Tc1/Tc2 ratio (50.0 +/- 11.1) was significantly
      increased in patients with MDS than in normal controls [(4.0 +/- 0.5)%, (5.8 +/-
      0.6)% and 13.4 +/- 2.7, respectively]. Levels of INF-gamma [(58.6 +/- 21.7)
      microg/L] and TNF-alpha [(15.7 +/- 3.8) microg/L] in marrow serum of MDS patients
      was markedly elevated compared to normal controls [0 and (0.3 +/- 0.2) microg/L,
      respectively]. An increased apoptosis index of nucleated cells was observed in
      MDS patients [(7.8 +/- 1.5)%] as compared to controls [(2.1 +/- 0.3)%, P < 0.05].
      The Th1 cell percentage showed a positive correlation with the levels of INF
      gamma and TNF-alpha (r = 0.38, P < 0.05 and r = 0.39, P < 0.05, respectively),
      and with apoptotic index of nucleated marrow cells in MDS patients (r = 0.33, P <
      0.05). Furthermore, a positive correlation was observed between INF-gamma, TNF
      alpha levels and apoptotic index of marrow cells (r = 0.74, P < 0.01 and r =
      0.73, P < 0.01, respectively). (2) Th1, Tc1 cells and Tc1/Tc2 ratio in MDS-RCMD
      patients was markedly elevated (P < 0.01) but did not in RCMD-RS, RAEB-1 and RAEB
      2 patients as compared to normal controls. (3) An elevation in the percentages of
      Th1, Tcl and Tc1/ Tc2 ratio was detected in patients with IPSS lower-risk but did
      not in higher-risk group as compared to controls. (4) Increased Th1 and Tc1
      percentages and Th1/Th2 and Tc1/Tc2 ratios were observed in RCMD patients with
      normal karyotype, but did not in those with abnormal karyotype. Conclusions
      Th1/Th2 and Tc1/Tc2 in bone marrow of MDS patients were unbalanced, polarizing to
      type I reaction especially in patients with RCMD subtype, IPSS lower-risk and
      normal karyotype. The increased Th1 cells in bone marrow may account for the
      increased apoptosis of nucleated marrow cells in MDS, through proapoptotic
      cytokines such as INF-gamma and TNF-alpha.

PMID- 18078134
TI  - [Study of mifepristone on reversing multidrug resistance of leukemic cell line
      K562/A02].
AB  - OBJECTIVE: To study whether progestogen antagonist mifepristone could reverse
      multidrug resistance of K562/A02 cells and its mechanisms. METHODS: MTT was used
      to study the proliferation of K562/A02 cells and sensitivity of K562/A02 cells to
      ADM after 72 hours treatment with mifepristone. Flow cytometry was used to assay
      the expression of P-glycoprotein and the mean fluorescent intensity of
      intracellular daunorubicin. The expressions of apoptosis related proteins (bcl-2,
      Bax and caspase-3) were assayed by immunohistochemistry and the glucosylceramide
      synthase mRNA expression by RT-PCR before and after mifepristone treatment.
      RESULTS: MTT assay revealed that 2.5, 5.0 and 10 micromol/L mifepristone did not
      affect the proliferation of K562/A02 cells, but enhanced the sensitivity of
      K562/A02 cells to ADM, by 1. 68-, 4.17- and 10.71- fold increase, respectively.
      Expression of P-gp in K562/A02 cells was (49.03 +/- 5.32)%, and was decreased to
      (28.60 +/- 2.13)% (P < 0.01) after 10 micromol/L mifepristone treatment for 72
      hours. and intracellular DNR accumulation in K562/A02 was (61.07 +/- 8.61)%, and
      was increased to (92.72 +/- 3.48)% (P < 0.01). After 10 micromol/L mifepristone
      treatment, the expression of bcl-2 protein was decreased from (56 +/- 9)% to (37
      +/- 6)% (P < 0.05), Bax and caspase-3 proteins was increased from (40 +/- 5)% to
      (87 +/- 10)% (P < 0.01), and from (36 +/- 7)% to (89 +/- 6)% (P < 0.01)
      respectively. RT-PCR analysis revealed that expression of glucosylceramide
      synthase mRNA was higher in K562/A02 than in K562 cells, whereas 10 micromol/L
      mifepristone significantly down-regulated its expression in K562/A02 cells.
      CONCLUSION: Mifepristone at 10 micromol/L could dose-dependently reverse the
      multidrug resistance of K562/A02 cells. The possible mechanisms are related with
      decreasing the expression of P-gp, regulating the expression of apoptosis related
      proteins and decreasing the expression of glucosylceramide synthase.

PMID- 18078135
TI  - Departicipating from Medicare and Medicaid programs.

PMID- 18078136
TI  - Inadequate instructions result in overdose death--a closed claim analysis.

PMID- 18078137
TI  - There are things only an outsider can tell you--practice management assessments
      identify and fix problems in your office.

PMID- 18078138
TI  - Medicine's national voice grows louder on uninsured.

PMID- 18078139
TI  - Flawed Medicare formula promotes capitationism.

PMID- 18078140
TI  - Caries prevention through the fluoridation of milk. A review.
AB  - The aim of this review is to give an overview of 50 years experience of milk
      fluoridation and draw conclusions about the applicability of the method.
      Fluoridated milk was first investigated in the early 1950s, almost simultaneously
      in Switzerland, the USA and Japan. Stimulated by the favourable results obtained
      from these early studies, the establishment of The Borrow Dental Milk Foundation
      (subsequently The Borrow Foundation) in England gave an excellent opportunity for
      further research, both clinical and non-clinical, and a productive collaboration
      with the World Health Organization from the early 1980s onwards. Numerous peer
      reviewed publications in international journals showed clearly the
      bioavailability of fluoride in milk, and increased concentrations of fluoride in
      saliva, dental plaque, dental enamel and dentine, and urine, after consumption of
      fluoridated milk. Clinical trials were initiated in the 1980s--some of these can
      be classed as randomised controlled trials, while most of the clinical studies
      were community preventive programs. These evaluations showed clearly that the
      optimal daily intake of fluoride in milk is effective in preventing dental
      caries. At present, milk fluoridation programs are running continuously in about
      ten countries of the world. Fluoridation of milk can be recommended as a caries
      preventive measure where the fluoride concentration in drinking water is
      suboptimal, caries experience in children is significant, and there is an
      existing school milk program. The program should aim to provide fluoridated milk
      for at least 200 days per year and should commence before the children are 4
      years of age.

PMID- 18078141
TI  - The influence of chronic apical periodontitis on oral and general health.
AB  - In healthy condition, the periodontal space between the root surface and the
      alveolar bone is relatively poor in cells. In case of root canal infection
      however, large number of immune-inflammatory cells infiltrate the periapical
      region of the affected teeth. A major issue is if and to what extent microbial
      and host cells contribute to lesion formation and whether the local inflammation
      may impair general health. The question is important as it may fundamentally
      influence the therapeutic strategy in patients with apical periodontitis. The aim
      of this paper is to review the results of recent experimental and clinical
      observations that investigate the importance of cellular interactions in exerting
      protective and destructive effects in periapical inflammatory lesions. The
      majority of studies indicate that the lesion would not develop in the absence of
      permanent release of bacteria and their by-products from the infected root canal.
      On the other hand, the formation of the classical granulation tissue is dependent
      on the presence and proper function of host cells and regulatory molecules. The
      dynamic encounter of root canal microbiota and the local immune system prevents
      overwhelming bacterial infiltration of the periradicular space but it is also
      connected with degenerative changes, most importantly bone resorption, resulting
      ultimately in tooth loss. However, by the use of proper endodontic methods, the
      lesion can be successfully treated in the majority of cases. Remineralization of
      the lost hard tissue will occur or the lesion will transform into an inert
      periapical scar.

PMID- 18078142
TI  - Emdogain in regenerative periodontal therapy. A review of the literature.
AB  - The goal of regenerative periodontal therapy is the reconstitution of the lost
      periodontal structures (i.e. the new formation of root cementum, periodontal
      ligament and alveolar bone). Results from basic research have pointed to the
      important role of the enamel matrix protein derivative (EMD) in the periodontal
      wound healing. Histological results from animal and human studies have shown that
      treatment with EMD promotes periodontal regeneration. Moreover, clinical studies
      have indicated that treatment with EMD positively influences periodontal wound
      healing in humans. The goal of the current overview is to present, based on the
      existing evidence, the clinical indications for regenerative therapy with EMD.
      Surgical periodontal treatment of deep intrabony defects with EMD promotes
      periodontal regeneration. The application of EMD in the context of non-surgical
      periodontal therapy has failed to result in periodontal regeneration. Surgical
      periodontal therapy of deep intrabony defects with EMD may lead to significantly
      higher improvements of the clinical parameters than open flap debridement alone.
      The results obtained following treatment with EMD are comparable to those
      following treatment with GTR and can be maintained over a longer period.
      Treatment of intrabony defects with a combination of EMD + GTR does not seem to
      additionally improve the results compared to treatment with EMD alone or GTR
      alone. The combination of EMD and some types of bone grafts/bone substitutes may
      result in certain improvements in the soft and hard tissue parameters compared to
      treatment with EMD alone. Treatment of recession-type defects with coronally
      repositioned flaps and EMD may promote formation of cementum, periodontal
      ligament and bone, and may significantly increase the width of the keratinized
      tissue. Application of EMD seems to provide better long-term results than
      coronally repositioned flaps alone. Application of EMD may enhance periodontal
      regeneration in mandibular Class II furcations. The clinical results are
      comparable to those obtained following GTR.

PMID- 18078143
TI  - The clinical and pathological symptoms of pregnancy epulis.
AB  - Examination of the oral cavity in 2260 pregnant women revealed 12 cases of
      pregnancy epulis, an incidence of 0.48%. In 9 of these 12 cases, spontaneous
      regression and recovery occurred 1-4 months after delivery. Despite the
      continuous conservative therapy, several surgical interventions were necessary in
      the remaining 3 pregnant women, due to the large size of the epulis and the
      bleeding that was difficult to stop. The authors provide a detailed description
      of the clinical symptoms (bleeding, difficulty of oral closure, loosening and
      migration of teeth) caused by large, multiple epulis instances during two
      pregnancies of one woman, together with the surgical interventions, the
      histopathologic examination and the immunohistochemical characteristics of the
      epulis.

PMID- 18078144
TI  - Disorders of glucose metabolism and risk of oral cancer.
AB  - Alcohol and tobacco are considered as major risk factors for oral cancer (OC). In
      the developed countries reduction of alcohol and tobacco consumption has achieved
      favorable decreasing trends in OC morbidity and mortality over the last decades.
      At the same time the earlier very high male-female OC ratio showed a declining
      tendency all over the world. This trend used to be simply interpreted by the
      increasing exposure to tobacco and alcohol among women. However, literary data
      support an enhanced prevalence of women among non-smoker non-drinker OC cases.
      These findings focused the attention for further underlying mechanisms in the
      initiation of OC, such as metabolic and hormonal disorders. Insulin resistant
      states (metabolic syndrome and type-2 diabetes) are sources of many human
      diseases. Reactive hyperinsulinemia, increased production of insulin-like growth
      factors, hyperglycemia and its serious consequences are all proven cancer
      promoters. Decreased blood perfusion of the tissues caused by diabetic macro- and
      microvascular lesions, extracellular matrix alterations, and defects of
      inflammatory and immunologic reactions in type-2 diabetes are also predictors of
      OC. The literary data and the authors' own results on their OC cases support the
      strong association of type-2 diabetes and increased cancer risk. Moreover, type-2
      diabetes has a significant impact on the local invasion and metastatic
      progression of OC. The correlations between glucose metabolism disorders and
      malignancies reveal new possibilities in the prevention and treatment of OC.

PMID- 18078145
TI  - Gene polymorphisms in periodontitis and hypodontia: methodological basis of
      investigations.
AB  - An increasing number of evidence supports the assumption that genetic factors
      have crucial role in the development of periodontitis and hypodontia. The
      strategic purpose of the authors is to identify the genetic background of these
      disorders and to map the gene polymorphisms involved in their development. As a
      first step of an experimental series, we aimed to set and optimize multiple
      individual gene polymorphism identification methods by the combination of
      polymerase chain reaction and restriction fragment length polymorphism analysis
      methods. We have successfully optimized eight single nucleotide polymorphism
      procedures that are potentially involved in periodontitis (IL-1 alpha -889, IL-1
      beta -511, IL-1 beta +3954, IL-6 -174, IL-10 -1082, TLR-4 -299, TLR-4 -399, TNF
      alpha -308), and another two that might be related to the appearance of
      hypodontia (PAX9 -1032, PAX9 -912). Besides the dominant allele, we also observed
      the presence of the rare allele in each polymorphism although at present we have
      a small sample number. These preliminary studies provide evidence for the
      feasibility of further investigations with large sample numbers comparing control
      and patient groups. These studies may lead to the development of new diagnostic
      strategies and provide novel tools for the early recognition of genetic
      predisposition and the primary control of the diseases. Furthermore, they project
      future therapeutic avenues for gene therapy in the cure and prevention of oral
      disorders.

PMID- 18078146
TI  - The American culture and health care.

PMID- 18078147
TI  - Homeric wounds in ancient Greek art.

PMID- 18078149
TI  - Lessons of a child.

PMID- 18078148
TI  - The patient who tried to cure his own cancer. Revisiting the story of Morris
      Abram's leukemia.

PMID- 18078150
TI  - Discharged to the streets: who cares?

PMID- 18078151
TI  - The lead files. A chronicle of ignorance, avarice, and progress.

PMID- 18078152
TI  - Megacode Guatemala.

PMID- 18078153
TI  - Burial at sea.

PMID- 18078154
TI  - A fragile web of understanding.

PMID- 18078155
TI  - The wayward eye.

PMID- 18078156
TI  - Things remembered.

PMID- 18078157
TI  - "Looking south to find the medicine of my heart".

PMID- 18078158
TI  - Endangered species indeed.

PMID- 18078159
TI  - Covenant.

PMID- 18078160
TI  - Intelligent design.

PMID- 18078161
TI  - [Eyeglass hematoma -- only a trifle accident].

PMID- 18078162
TI  - [Are white coats really germ throwers?].

PMID- 18078164
TI  - [Young woman with acute pain in the right hypogastric region: falsely suspected
      appendix].

PMID- 18078163
TI  - [The infernal torturing sensation ].

PMID- 18078165
TI  - [Difficult treatment and frequent recurrences of lung cancer. Only one in ten
      survives].

PMID- 18078166
TI  - [Lung tumours under the microscope].
AB  - Only through a precise pretherapeutic characterization is it possible to develop
      an optimal, specific treatment for lung carcinoma. In addition to confirming the
      diagnosis, the task of the pathologist is to characterize the tumour in terms of
      histology, grade, stage and if necessary, special properties. Because a
      histological assessment is subject to many sources of errors, interpretation of
      the often very small tumour samples should be performed only in conjunction with
      clinical and imaging findings.

PMID- 18078167
TI  - [Surgical therapy of bronchial carcinoma].
AB  - Chest surgery is a fundamental component of the interdisciplinary diagnostic and
      therapeutic procedures for lung cancer. NSCLC is usually treated by surgical
      resection. The long-term prognosis after chest surgery decidedly depends on the
      tumour stage. Integration of surgery into a combined therapeutic concept
      (multimodal, adjuvant or neoadjuvant) improves the therapeutic outcome of
      advanced cases.

PMID- 18078168
TI  - [Patient information. Finally smoke-free!].

PMID- 18078169
TI  - [Constipation in patients with diabetes mellitus].
AB  - Up to 60% of the patients with diabetes mellitus suffer from gastrointestinal
      tract symptoms that arise pathogenetically from a disturbance of the autonomous
      nervous system. Patient age, disease duration and poor control of diabetes
      mellitus correlate positively with the presence of gastrointestinal symptoms.
      Chronic constipation, in addition to diarrhoea, gall bladder dysfunction and
      incontinence, is increasingly regarded as a serious problem and for the first
      time, is now considered in the current guidelines of the professional societies.
      Modern diagnosis and treatment facilitate systematic control of the symptoms.
      Treatment necessitates long-term intake of laxatives, proper diabetes control and
      other accompanying general measures such as adequate amounts of liquids, dietary
      fibre and exercise. Motility and secretion-stimulating, osmotically active or
      locally applied laxatives are used. Slow transit constipation, which is typically
      observed in diabetics, can be best controlled with polyethylene glycol, bisacodyl
      or sodium picosulphate.

PMID- 18078170
TI  - [Acute monarthritis].
AB  - Common causes of acute monarthritis are osteoarthritis, an acute attack of gout
      or other crystal arthropathies in older patients or a reactive arthritis or
      gonococcal arthritis in younger patients. The differential diagnosis should
      primarily rule out septic arthritis. An arthrocentesis with a microbiological
      work up and a fresh specimen should be prepared for the diagnosis of crystal
      arthropathies and if an infectious origin is suspected or if nothing remarkable
      was found during the primary examination. Further diagnosis und therapy should be
      performed by a specialist.

PMID- 18078171
TI  - [New data on hypoglycemia risk and beta cell function].

PMID- 18078172
TI  - [Online accounting: to change now?].

PMID- 18078173
TI  - The MDT five-minute interview.

PMID- 18078174
TI  - The natural pace of healing.
AB  - Injuries are often seen as unfortunate, inconvenient events, the recovery from
      which, for economic and social reasons, should be accelerated. However, nature is
      adept at repairing many injured tissues and we should refrain from unnecessary
      and illogical attempts to interfere with natural processes.

PMID- 18078175
TI  - Phthalate labelling of medical devices.
AB  - In the European Union, the use of Di(2-ethylhexyl)phthalate (DEHP) in medical
      devices has been under serious pressure. A proposed ban on its use was avoided
      and changed into a labelling requirement. This article reports the dramatic
      political developments that resulted in this requirement and highlights some new
      alternative plasticisers that can be used if poly(vinyl chloride) devices without
      DEHP are required in the future.

PMID- 18078176
TI  - Tailoring established polymers for medical applications.
AB  - Polymers can be tailored for specific biomedical applications by synthesis,
      processing or surface modification. Knowledge-based choice of comonomers for
      acrylonitrile based copolymers influences the interaction profile with specific
      cell lines and blood. Processing or surface modification of poly(ether imides)
      results in materials having complex three-dimensional structures and/or specific
      adsorption profiles. Potential applications are dialysis, gas separation,
      cell/tissue systems, apheresis, and bioreactors.

PMID- 18078177
TI  - An implantable microsystem as a vision prosthesis.
AB  - Blindness is often the result of degeneration of the light sensitive rods and
      cones of the retina in conditions such as retinitis pigmentosa and macula
      degeneration. An implantable vision prosthesis has been developed that
      electrically stimulates the retinal ganglion cells in such a way that action
      potentials in retinal ganglion cells are evoked, causing a visual sensation in
      the visual cortex. Clinical trials are about to be conducted.

PMID- 18078178
TI  - Auditing device clinical studies for US requirements.
AB  - Medical device manufacturers conducting clinical studies outside the United
      States (US) to support US regulatory submissions should be prepared to show that
      these studies are conducted in a manner that will be acceptable to the Food and
      Drug Administration. This article discusses the audits that can be conducted to
      assess this acceptability.

PMID- 18078179
TI  - Nanomedicine and risk: further perspectives.
AB  - The first article in this new series on nanomedicine, advocated the need for more
      risk research in the field of medical nanotechnology. Here, some further aspects
      of risk at the nanoscale are considered and suggestions are made on where this
      risk effort should be focused.

PMID- 18078180
TI  - Biocompatible materials developments for new medical implants.
AB  - Recent work on modifying silicone rubber to improve water permeability and
      biocompatibility is described. In addition, modifications to the interface
      between an active implanted device and the body are reported, which have led to
      reduced power consumption and improved device performance.

PMID- 18078181
TI  - Precious metals: materials of diversity.
AB  - The properties of precious metals and their alloys make them suitable for an
      expanding number of applications. Their great capacity to be cold worked and
      other valuable characteristics for medical device applications are outlined.

PMID- 18078182
TI  - Ireland: delivering today and tomorrow.
AB  - The Irish medical device industry employs, per capita, the highest number of
      people of all the medical technology sectors in the European Union. The industry
      is buoyant with many new initiatives underway to ensure its future growth.

PMID- 18078183
TI  - Video measurement systems take hold of manufacturing.

PMID- 18078184
TI  - Thin film metrology.
AB  - Thin film metrology is suitable for characterising and performing quality control
      of a variety of coatings and films used in medical applications. The capabilities
      of today's systems are described.

PMID- 18078185
TI  - The UK: improving market access.
AB  - The future prosperity of the United Kingdom medical technology industry depends
      on better access to its domestic market. Yet the persisting slowness of the
      National Health Service to adopt new products is driving investment abroad.

PMID- 18078186
TI  - [The chief internist of the general internal medicine department of a regional
      hospital: an endangered species?].

PMID- 18078187
TI  - [How to organize the emergency department of primary care hospitals in the
      future? Nyon's regional hospital experience].
AB  - Optimization of patients flow can decrease the overcrowding of the emergency
      department (ED) and improve the level of patient's satisfaction. The prospective
      analysis of 502 consecutive admissions at the Nyon regional hospital's ED shows a
      mean length of stay (LOS) of 145 minutes, for a majority of low-severity cases
      admitted during working hours. A significant LOS variability reveals transient
      episodes of overcrowding, which lead to an increase in the LOS of mainly
      ambulatory patients. Our analysis shows that both the ED's structure and the
      medical organization create a gap between ED performance as care provider and the
      patients' expectations, and suggests that a separation of low-versus high
      complexity cases is necessary. Patients' flow analysis can detect ED overcrowding
      and may help find the appropriate solutions to reduce it.

PMID- 18078188
TI  - [Hospital infection control--beyond the hospital].
AB  - Health care related infections are expensive untoward events, not only in terms
      of morbidity and mortality, but also cost. Prevention is essential, as well as
      limiting dissemination. Specify measures refer usually to hospital hygiene.
      However, health care tend to be provided more and more outside of the acute care
      hospital, with increasing complexity and thus risk for health care related
      infections. This risk varies according to patient's characteristics as well as
      environmental parameters. Consequently, it is essential to adapt preventive
      measures to situations such as home health care or nursing homes. We describe a
      model of regional organization for infection control in various health care
      settings.

PMID- 18078189
TI  - [Diabetes: integrated hospital and home care].
AB  - Intrahospital hyperglycemia (> 6,1 mol/l fasting, > 10 mmol/l non-fasting) is
      associated with a poor outcome even in non-diabetic patients, and warrants tight
      glycemic controls often with insulin therapy. The preferred regimen termed
      "intensive therapy" meets basal requirements (approximately 50% daily needs) with
      a long acting preparation, supplemented with short/ rapid insulins, according to
      meals. A multidisciplinary team involving specialized nurses, diabetologists,
      dieticians and podiatrists should help in-hospital staff implement such insulin
      therapy and provide patient management which would continue when the patient is
      discharged providing assistance to the patient, family and primary physician.
      Improving the patient's understanding with regard to diabetes complications and
      management will result in better compliance and therefore, disease control.

PMID- 18078190
TI  - [The perioperative period: how drugs should be managed?].
AB  - Medication use during the perioperative period can raise problems in surgical
      patients. Elderly patients are especially at risk because of polymedication.
      Risks pertaining to each drug should be carefully evaluated. For example, several
      drugs can affect coagulation and discontinuation of others can lead to withdrawal
      symptoms. We suggest here recommendations based on recent publications. It should
      be kept in mind that, apart from the drug itself, the patient status as well as
      the surgical procedure also influence the decision to stop or continue a
      medication. Moreover, it is important to plan to restart any discontinued drug in
      order to avoid unintended treatment failure after hospital discharge.

PMID- 18078191
TI  - [The role of biomarkers in the evaluation of the patient with dyspnea, chest pain
      or syncope].
AB  - This paper reviews the use of 3 biomarkers, BNP (brain natriuretic peptide),
      troponins and D-dimers, in 3 common clinical situations: the patient presenting
      with dyspnea, with chest pain or with syncope. The diagnostic utility and the
      pronostic implications of a positive as well as a negative test are reviewed
      according the most recent medical literature. Interpretation of false positive
      and false negative results is also discussed. Familiarity with the use of these
      tests is increasingly important because practicioners will be soon provided with
      rapid bed-side multi-markers assays to help them in their differential diagnosis
      while examining the patient.

PMID- 18078192
TI  - [Tick-borne encephalitis in the North part of the canton de Vaud].
AB  - Tick-borne encephalitis (TBE) is described in Switzerland since 1969. More than
      200 cases are reported every year to the Federal office of public health (FOPH)
      and new sites of endemic disease have been documented recently, in particular in
      the North part of the canton de Vaud. The aim of this article is to review the
      clinical pictures of 11 patients hospitalised in Yverdon-les-Bains with a
      diagnosis of TBE between 2003 and August 2007. The occurrence of 5 new cases
      exposed in the North part of the canton de Vaud over these last 18 months
      confirms the presence of endemic foci in this area and should prompt the
      vaccination against the MEVE which is recommended by the FOPH in endemic zones.
      The sequels of MEVE being observed mainly in the elderly, vaccination should be
      afforded also to this group of patients.

PMID- 18078193
TI  - [Cancer of the endometrium].

PMID- 18078194
TI  - [What is the role of equality in postgraduate education in medicine? Questions
      for Magdalena Rosende, sociologist].

PMID- 18078195
TI  - [The fight against the AIDS-tuberculosis co-epidemic (I)].

PMID- 18078196
TI  - [Some disturbing truths on female sexual mutilation].

PMID- 18078197
TI  - [These days the surrogate mother is lucky].

PMID- 18078198
TI  - [New light on the genetics of HIV infection].

PMID- 18078199
TI  - [Diversity].

PMID- 18078200
TI  - Shape variability and classification of human hair: a worldwide approach.
AB  - Human hair has been commonly classified according to three conventional ethnic
      human subgroups, that is, African, Asian, and European. Such broad classification
      hardly accounts for the high complexity of human biological diversity, resulting
      from both multiple and past or recent mixed origins. The research reported here
      is intended to develop a more factual and scientific approach based on physical
      features of human hair. The aim of the study is dual: (1) to define hair types
      according to specific shape criteria through objective and simple measurements
      taken on hairs from 1442 subjects from 18 different countries and (2) to define
      such hair types without referring to human ethnicity. The driving principle is
      simple: Because hair can be found in many different human subgroups, defining a
      straight or a curly hair should provide a more objective approach than a
      debatable ethnicity-based classification. The proposed method is simple to use
      and requires the measurement of only three easily accessible descriptors of hair
      shape: curve diameter (CD), curl index (i), and number of waves (w). This method
      leads to a worldwide coherent classification of hair in eight well-defined
      categories. The new hair categories, as described, should be more appropriate and
      more reliable than conventional standards in cosmetic and forensic sciences.
      Furthermore, the classification can be useful for testing whether hair shape
      diversity follows the continuous geographic and historical pattern suggested for
      human genetic variation or presents major discontinuities between some large
      human subdivisions, as claimed by earlier classical anthropology.

PMID- 18078201
TI  - Estimating final height from parental heights and sex in Taiwanese.
AB  - We have developed a simple function for accurately estimating target height for
      use in evaluating growth and growth-promoting therapies in Taiwanese children.
      The heights of parents and their adult offspring born in the 1970s were
      determined in 1229 healthy families who accompanied another family member to our
      pediatric clinic. We directly measured the heights of the population-based cohort
      of adult offspring. The heights of their parents were based on self-report. Both
      the parents and their offspring were healthy. The increases in height between the
      two generations were 1.49-3.19 cm for boys and 2.03-2.61 cm for girls. These
      increases lie between those reported for Chinese children in Hong Kong (4.2-4.8
      cm) and children in Sweden (0.7-1.0 cm). Final height was underestimated using
      the corrected midparental height method and was overestimated using the final
      parental height model developed from Swedish data. We developed a new linear
      model by fitting our data: boy height = 79.3 + 0.56 (midparental height); girl
      height = 35.2 + 0.76 (midparental height). The intercept and slope of the model
      are similar to those reported for Swedish girls but not to those reported for
      Swedish boys. Use of the new equations derived from our data may increase the
      accuracy of estimates of target height in Taiwanese children. The intermediate
      position of our fairly representative Taiwanese sample in both final height and
      generational increases in final height may reflect an intermediate stage between
      the Swedes and Hong Kong Chinese in the secular trend of heights.

PMID- 18078202
TI  - Low frequency of the deltaAF508 mutation of the CFTR gene in a highly admixed
      population in Bahia, Brazil.
AB  - Cystic fibrosis (CF) is the most common autosomal recessive disease in the
      European (Caucasian) population, with an incidence of 1:2000 to 1:8000. The
      deltaF508 mutation (66%) is predominant among more than 1300 different mutations
      of the CFTR gene. The population of the state of Bahia, in northeastern Brazil,
      is highly admixed (mainly African and Portuguese descendants), and so far, no
      study has been carried out to assess the molecular basis of CF in this
      population. We determined the deltaF508 mutation frequency in 503 individuals
      from the general population of Salvador, the capital of the state of Bahia, and
      in 144 CF patients from several cities in Bahia. In the general population
      samples we found 4 individuals heterozygous for the deltaF508 mutation (allele
      frequency of 0.4%). This frequency was lower than that found in the state of Rio
      de Janeiro, in southeastern Brazil, and similar to that reported for the state of
      Parana, in the far south. In the CF patients we found 9 heterozygous individuals
      and 8 homozygous individuals (allele frequency of 8.68%) for the deltaF508
      mutation. This frequency is considerably lower than the average frequency of CF
      in the world population and in the Brazilian CF population of European ancestry
      (47%). These data could be explained by the intense admixture among the
      population in Bahia, and they suggest a heterogeneous molecular basis for CF in
      this area of Brazil.

PMID- 18078203
TI  - Genotype frequencies of polymorphic GSTM1, GSTT1, and cytochrome P450 CYP1A1 in
      Mexicans.
AB  - The genotype frequencies of three metabolic polymorphisms were determined in a
      sample of a typical community in central Mexico. CYP1A1*3, GSTM1, and GSTT1
      polymorphisms were studied in 150 donors born in Mexico and with Mexican
      ascendants; with respect to ethnicity the subjects can be considered Mestizos.
      PCR reactions were used to amplify specific fragments of the selected genes from
      genomic DNA. An unexpected 56.7% frequency of the CYP1A1*3 allele (which depends
      on the presence of a Val residue in the 462 position of the enzyme, instead of
      Ile) was found, the highest described for open populations of different ethnic
      origins (i.e., Caucasian, Asian, African, or African American). The GSTM1 null
      genotype was found with a frequency of 42.6%, which is not different from other
      ethnicities, whereas the GSTT1 null genotype had a frequency of 9.3%, one of the
      lowest described for any ethnic group but comparable to the frequency found in
      India (9.7%). The frequency of the combined genotype CYP1A1*3/*3 and the GSTM1
      null allele is one of the highest observed to date (or perhaps the highest):
      13.7% among all the ethnicities studied, including Caucasians and Asians, whereas
      the combination of CYP1A1*3/*3 with the GSTT1 null allele reached only 2.8%. The
      GSTM1 null allele combined with the GSTT1 null allele, on the other hand, has one
      of the lowest frequencies described, 4.24%, comparable to the frequencies found
      in African Americans and Indians. Finally, the combined CYP1A1*3/*3, GSTM1 null
      allele, and GSTT1 null allele genotype could not be found in the sample studied;
      it is assumed that the frequency of carriers of these combined genotypes is less
      than 1%. CYP1A1*3 and CYP1A1*2 polymorphisms were also evaluated in 50 residents
      in a community of northern Mexico; the CYP1A1*3 frequency was 54%, similar to
      that found in the other community studied, and the CYP1A1*2 frequency was 40%,
      which is high compared to Caucasians and Asians but comparable to the frequency
      found in Japanese and lower than the frequency found in Mapuche Indians.
      Haplotype frequencies for these CYP1A1 polymorphisms were estimated, and a
      linkage disequilibrium value (D) of 0.137 was calculated.

PMID- 18078204
TI  - Characterization of mtDNA haplogroups in 14 Mexican indigenous populations.
AB  - In this descriptive study we investigated the genetic structure of 513 Mexican
      indigenous subjects grouped in 14 populations (Mixteca-Alta, Mixteca-Baja, Otomi,
      Purepecha, Tzeltal, Tarahumara, Huichol, Nahua-Atocpan, Nahua-Xochimilco, Nahua
      Zitlala, Nahua-Chilacachapa, Nahua-Ixhuatlancillo, Nahua-Necoxtla, and Nahua
      Coyolillo) based on mtDNA haplogroups. These communities are geographically and
      culturally isolated; parents and grandparents were born in the community. Our
      data show that 98.6% of the mtDNA was distributed in haplogroups A1, A2, B1, B2,
      C1, C2, D1, and D2. Haplotype X6 was present in the Tarahumara (1/53) and Huichol
      (3/15), and haplotype L was present in the Nahua-Coyolillo (3/38). The first two
      principal components accounted for 95.9% of the total variation in the sample.
      The mtDNA haplogroup frequencies in the Purepecha and Zitlala were intermediate
      to cluster 1 (Otomi, Nahua-Ixhuatlancillo, Nahua-Xochimilco, Mixteca-Baja, and
      Tzeltal) and cluster 2 (Nahua-Necoxtla, Nahua-Atocpan, and Nahua-Chilacachapa).
      The Huichol, Tarahumara, Mixteca-Alta, and Nahua-Coyolillo were separated from
      the rest of the populations. According to these findings, the distribution of
      mtDNA haplogroups found in Mexican indigenous groups is similar to other
      Amerindian haplogroups, except for the African haplogroup found in one
      population.

PMID- 18078205
TI  - Genetic kinship among an isolated Adi tribe of Arunachal Pradesh: isonymy in the
      Adi Panggi.
AB  - Isolated tribes in remote areas are important for genetic studies, and one such
      little known subtribe of the Adi tribe, namely, the Adi Panggi (Pangi) of the
      Upper Siang District of Arunachal Pradesh, India, was studied for surname
      distribution to deduce the deviation from random mating and genetic kinship
      between villages. The estimates of homonymy (homozygosity) vary between villages;
      husbands show wider variation (0.009 to 0.23) than wives (0.005 to 0.054). The
      remote villages of Sumsing and Sibum and Geku Town show lower entropy among
      husbands' surnames than among Panggi wives. The highest equivalent surname number
      was found among Sibum husbands (9.9), Panggi wives (12.6), and Panggi and non
      Panggi wives (13.5). The estimates of unbiased random isonymy among husbands and
      wives together show the smallest values in Sibum (0.05) and the highest values in
      Sumsing and Ramku (0.16). The random and nonrandom components of the inbreeding
      coefficient show avoidance of inbreeding among the Panggi villages (-0.012 to 
      0.27) except in Sibum (0.012). Genetic kinship between villages based on the Mij
      distance shows different clusters of villages among husbands and wives. Both the
      Panggi wives and the Panggi and non-Panggi wives show a similar pattern of
      clustering between villages. The wide homonymy variation between villages among
      the patrilocal Adi Panggi indicates differential genetic kinetics among husbands
      and wives, avoidance of inbreeding, and female-oriented differential gene flow
      with little effect on the overall intervillage genetic kinship.

PMID- 18078206
TI  - HLA class I and class II polymorphism in three Sicilian populations.
AB  - Two human leukocyte antigen (HLA) class I loci (HLA-A and HLA-B) and one class II
      locus (HLA-DR) were typed at the DNA level in the Sicilian population. Study
      participants were of Sicilian origin (183 for class I loci and 260 for class II
      loci) and live in three towns, chosen on the basis of geographic position and
      different historical events. These towns are Sciacca (southwest Sicily, located
      at sea level, conquered by Arabs in A.D. 814), Piana degli Albanesi (northwest
      Sicily, 720 m above sea level, has maintained religious, cultural, and linguistic
      peculiarities traced to Albanian settlement in 1488), and Troina (northeast
      Sicily, 1120 m above sea level, known as the first settlement of Normans). The
      assumptions underlying the study of genetic structure, based on HLA allele
      polymorphism, are that these three towns are located in areas that can be
      distinguished according to historical criteria and that they are likely to have
      contributed to cultural and probably genetic differences. As such, the high
      frequency of some alleles in Sciacca and Troina seems to be correlated with
      Greek, Phoenician, North African, and Arab influence. In accordance with
      different human settlements in Sicily, we found that the HLA allele frequencies
      support the existence of genetic differentiation between the western and eastern
      sides of Sicily. This separation is attributed to Greek colonization in the east
      and to Phoenician-Carthaginian-Arab influence in the west. Moreover, the
      comparisons of all allele frequencies between Mediterranean and AfrIcan
      populations show the same trend, highlighting in some cases European origin and
      in other cases non-European origin.

PMID- 18078207
TI  - Intertribal and temporal allele-frequency variation at the ABO locus among Tibeto
      Burman-speaking Adi subtribes of Arunachal Pradesh, India.
AB  - We studied the distribution of ABO blood group frequencies of the Galo and
      Mishing subtribes of the Adi tribal cluster in East Siang District, Arunachal
      Pradesh, India, in order to investigate the intertribal and temporal allelic
      variation. Blood groups O and AB showed higher frequencies (28.4%, 27.4%) in the
      Galo, whereas group O (45%) was predominant in the Mishing. Allele r is
      significantly different in the Galo (44.6%) and Mishing (60.3%). The chi-square
      test indicated significant deviations from Hardy-Weinberg equilibrium. Adi tribes
      show high heterogeneity and indicate significant temporal variation in ABO
      genotype frequencies in the Galo, Mishing, and Padam, whereas the Panggi, a small
      isolated subtribe of Adi, show similar and stable frequencies.

PMID- 18078208
TI  - Importance of acetylator phenotype in the identity of Asian populations.
AB  - The Marma, Tripura, and Chakma are tribal populations of South Asian countries
      such as Bangladesh. The populations are thought to be immigrants who started
      moving from their original home in the Far East toward the west and south. We
      randomly selected 80 Marma, 53 Tripura, and 43 Chakma to determine acetylation
      capacity and acetylator phenotype. The mean acetylation capacities were 63% in
      the Marma, 65% in the Tripura, and 70% in the Chakma. The acetylator phenotype
      was bimodally distributed as fast and slow acetylator. The frequencies of fast
      acetylator were 83% in the Marma, 89% in the Tripura, and 88% in the Chakma.
      According to acetylation capacity, the tribes are different from the founder
      nontribal populations of Bangladesh. They identify themselves as having a
      separate single population origin. The frequency of fast acetylator predicted
      served as the acetylator status of the Far East Asian population. The segregation
      of populations by acetylator phenotype on geographic longitude might be
      appropriate for geonational identification of Asian populations.

PMID- 18078209
TI  - Tough road lies ahead on nurse pay.

PMID- 18078210
TI  - 'Nurses need to encourage patients to self-care differently, rather than more'.

PMID- 18078211
TI  - A little humour could make hospitals healthier.

PMID- 18078212
TI  - How it feels to nurse at a 'failing' trust.

PMID- 18078213
TI  - 'I've seen a great shift in HIV care'.

PMID- 18078214
TI  - Improving falls prevention and standards of fracture care.

PMID- 18078215
TI  - Bowel care. Part 6--administration of a suppository.

PMID- 18078216
TI  - Supporting failing students in practice. 1: Assessment.
AB  - This two-part unit examines the issue of nursing students who fail in clinical
      practice. Part 1 explores reasons for failure, assessment and the emotional
      challenges mentors may face when supporting failing students.

PMID- 18078217
TI  - An overview of faecal incontinence in children.
AB  - Anne Weaver and Penny Dobson outline the current practice for assessment and
      treatment of faecal incontinence in children.

PMID- 18078218
TI  - Transanal irrigation after spinal cord injury.
AB  - Maureen Coggrave explains why and how transanal irrigation is used for bowel
      management following spinal cord injury.

PMID- 18078219
TI  - The role of symmetry in attraction to average faces.
AB  - Although many studies have demonstrated that average faces tend to be attractive,
      few studies have examined the extent to which symmetry contributes to the
      attractiveness of average faces. Such studies are potentially important, however,
      because average faces are highly symmetric and increasing the symmetry of face
      images increases their attractiveness. Here we demonstrate that increasing
      averageness of 2-D face shape independently of symmetry is sufficient to increase
      attractiveness, indicating that preferences for symmetry cannot solely explain
      the attractiveness of average faces. Additionally, we show that averageness
      preferences are significantly weaker when the effects of symmetry are controlled
      for using computer graphic methods than when the effects of symmetry are not
      controlled for, suggesting that symmetry contributes to the attractiveness of
      average faces. Importantly, this latter finding was not explained by the greater
      perceived similarity between versions offaces that varied in averageness, but not
      symmetry, than between versions of faces that varied in both averageness and
      symmetry.

PMID- 18078220
TI  - The contrasting impact of global and local object attributes on Kanizsa figure
      detection.
AB  - Studies on the involvement of object completions in search for illusory figures
      have so far reported equivocal results. We have addressed this issue by
      investigating at which level object attributes in Kanizsa figures influence
      search. Employing a paradigm that investigated global and local attributes in the
      composition of distractors with relation to target composition, we report a
      selective involvement of multilevel processing upon detection. Four experiments
      demonstrate that global surface information, but not the surrounding global
      contour, determines the speed of Kanizsa figure detection. By contrast, local
      inducer information is encoded far less efficiently in search than processes
      computing the global object. Our conclusions are that surface filling-in acts as
      a major determinant of search, but depends on the relevance of the particular
      hierarchical level (local or global) coding the target.

PMID- 18078221
TI  - Impaired temporal discrimination within the attentional blink.
AB  - Yeshurun and Levy (2003) reported that temporal discrimination performance of a
      visual stimulus benefits when spatial attention is oriented away from its
      location. In the present study, we investigated whether this negative influence
      of attention on temporal discrimination performance is restricted to transient
      spatial attention or might generalize to other paradigms of attention. We
      employed the attentional blink (AB) paradigm and required either a spatial
      (Experiment 1) or a temporal discrimination task (Experiment 2). The results of
      both experiments revealed a performance decrement if attention was temporally
      unavailable during the AB and a recovery with increasing attentional
      availability. Thus, contrary to the results of Yeshurun and Levy, the absence of
      attention decreased temporal discrimination performance in this paradigm. We
      hypothesize that attention which operates at different processing levels might
      exert differential effects on temporal stimulus processing.

PMID- 18078222
TI  - Role of Gestalt grouping in selective attention: evidence from the Stroop task.
AB  - Selective attention has been intensively studied using the Stroop task. Evidence
      suggests that Stroop interference in a color-naming task arises partly because of
      visual attention sharing between color and word: Removing the target color after
      150 msec reduces interference (Neumann, 1986). Moreover, removing both the color
      and the word simultaneously reduces interference less than does removing the
      color only (La Heij, van der Heijden, & Plooij, 2001). These findings could also
      be attributed to Gestalt grouping principles, such as common fate. We report
      three experiments in which the role of Gestalt grouping was further investigated.
      Experiment I replicated the reduced interference, using words and color patches.
      In Experiment 2, the color patch was not removed but only repositioned (<2
      degrees) after 100 msec, which also reduced interference. In Experiment 3, the
      distractor was repositioned while the target remained stationary, again reducing
      interference. These results indicate a role for Gestalt grouping in selective
      attention.

PMID- 18078223
TI  - Parallel processing of stimulus features during RSVP: evidence from the second
      response.
AB  - When observers are asked to report a feature of a single target displayed in
      rapid serial visual presentation, they frequently make errors. Most frequently, a
      feature from the to-be-reported dimension pertaining to a stimulus presented near
      the target is reported. These migrations are so-called illusory conjunctions in
      the time domain. From parallel models, it is proposed that during the
      presentation of the series, the response features of the stimuli are extracted.
      If a high rate of presentation does not enable proper binding processes, the
      system could base its response on sophisticated guessing on the basis of the
      relative levels of activation of the available response features. However, the
      multiple extractions assumption has not received direct empirical support. We
      report two experiments in which the observers had to report their first and
      second response candidates. This double response paradigm makes it possible to
      test the assumption that more than one response feature is available for making a
      response. Furthermore, the application of the constant ratio rule (following
      Botella, Barriopedro, & Suero's, 2001, model) to the first responses allows
      predictions for the ratios between choices of the items for the second responses.
      The correlations between the observed and the predicted response proportions were
      .887 and .956 in the two experiments. This high predictive capacity indicates,
      first, that the observers have more than one response available, among which to
      choose, and second, that the choice among responses is determined largely in the
      same way for both, first and second responses. Nevertheless, the small errors in
      prediction are further reduced if a proportion of pure guesses is assumed in the
      second responses. These are probably due to memory losses, misidentifications of
      the features, and other factors impairing performance in second responses in
      comparison with first responses.

PMID- 18078224
TI  - Moving along the number line: operational momentum in nonsymbolic arithmetic.
AB  - Can human adults perform arithmetic operations with large approximate numbers,
      and what effect, if any, does an internal spatial-numerical representation of
      numerical magnitude have on their responses? We conducted a psychophysical study
      in which subjects viewed several hundred short videos of sets of objects being
      added or subtracted from one another and judged whether the final numerosity was
      correct or incorrect. Over a wide range of possible outcomes, the subjects'
      responses peaked at the approximate location of the true numerical outcome and
      gradually tapered off as a function of the ratio of the true and proposed
      outcomes (Weber's law). Furthermore, an operational momentum effect was observed,
      whereby addition problems were overestimated and subtraction problems were
      underestimated. The results show that approximate arithmetic operates according
      to precise quantitative rules, perhaps analogous to those characterizing movement
      on an internal continuum.

PMID- 18078225
TI  - Locus of the intensity effect in simple reaction time tasks.
AB  - Evidence is still inconclusive regarding the locus of the stimulus intensity
      effect on information processing in reaction tasks. Miller, Ulrich, and
      Rinkenauer (1999) addressed this question by assessing the intensity effect on
      stimulus- and response-locked lateralized readiness potentials (LRPs) as indices
      of the sensory and motor parts of reaction time (RT). In the case of visual
      stimuli, they observed that application of brighter stimuli resulted in a
      shortening of RT and stimulus-locked LRP (S-LRP), but not of response-locked LRP
      (R-LRP). The results for auditory stimuli, however, were unclear. In spite of a
      clear RT reduction due to increased loudness, neither S-LRP nor R-LRP onset was
      affected. A reason for this failure might have been a relatively small range of
      intensity variation and the type of task. To check for this possibility, we
      performed three experiments in which broader ranges of stimulus intensities and
      simple, rather than choice, response tasks were used. Although the intensity
      effect on the R-LRP was negligible, S-LRP followed RT changes, irrespective of
      stimulus modality. These findings support the conclusion that stimulus intensity
      exerts its effect before the start of motoric processes. Finally, S-LRP and R-LRP
      findings are discussed within a broader information-processing perspective to
      check the validity of the claim that S-LRP and R-LRP can, indeed, be considered
      as pure estimates of the duration of sensory and motor processes.

PMID- 18078226
TI  - The contribution of rapid visual and auditory processing to the reading of
      irregular words and pseudowords presented singly and in contiguity.
AB  - This study examined the relative involvement of rapid auditory and visual
      temporal resolution mechanisms in the reading of phonologically regular
      pseudowords and English irregular words presented both in isolation and in
      contiguity as a series of six words. Seventy-nine undergraduates participated in
      a range of reading, visual temporal, and auditory temporal tasks. The correlation
      analyses suggested a general timing mechanism across modalities. There were more
      significant correlations between the visual temporal measures and irregular word
      reading and between the auditory measures and pseudoword reading. Auditory gap
      detection predicted pseudoword reading accuracies. The low temporal frequency
      flicker contrast sensitivity measure predicted the accuracies of isolated
      irregular words and pseudowords presented in contiguity. However, when a combined
      speed-accuracy score was used, visible persistence at both low and high spatial
      frequencies and auditory gap detection were active in the reading of pseudowords
      presented in contiguity. Sensory processing skills in both visual and auditory
      modalities accounted for some of the variance in the reading performance of
      normal undergraduates, not just reading-impaired students.

PMID- 18078227
TI  - Visual contribution to the multistable perception of speech.
AB  - The multistable perception of speech, or verbal transformation effect, refers to
      perceptual changes experienced while listening to a speech form that is repeated
      rapidly and continuously. In order to test whether visual information from the
      speaker's articulatory gestures may modify the emergence and stability of verbal
      auditory percepts, subjects were instructed to report any perceptual changes
      during unimodal, audiovisual, and incongruent audiovisual presentations of
      distinct repeated syllables. In a first experiment, the perceptual stability of
      reported auditory percepts was significantly modulated by the modality of
      presentation. In a second experiment, when audiovisual stimuli consisting of a
      stable audio track dubbed with a video track that alternated between congruent
      and incongruent stimuli were presented, a strong correlation between the timing
      of perceptual transitions and the timing of video switches was found. Finally, a
      third experiment showed that the vocal tract opening onset event provided by the
      visual input could play the role of a bootstrap mechanism in the search for
      transformations. Altogether, these results demonstrate the capacity of visual
      information to control the multistable perception of speech in its phonetic
      content and temporal course. The verbal transformation effect thus provides a
      useful experimental paradigm to explore audiovisual interactions in speech
      perception.

PMID- 18078228
TI  - Top-down inhibition of search distractors in parallel visual search.
AB  - In three experiments, we examined distractor inhibition in parallel ("pop-out")
      visual search. Distractor inhibition was measured in terms of reaction time (RT)
      to a simple luminance increment probe presented, after the search task response,
      at display locations that either contained a search distractor (on-probe) or were
      blank (off-probe). When the search stimuli remained in view, the on-probe
      (relative to off-probe) RT cost was larger than in a baseline condition in which
      observers had only to passively view, rather than search, the display. This
      differential on-probe RT cost, which discounts effects of masking, was
      interpreted as a measure of distractor inhibition associated with target
      selection in parallel visual search. Taken together, the results argue that the
      distractor inhibition is an object-based and local phenomenon that affects all
      distractors (of a particular type) in an equal manner.

PMID- 18078229
TI  - Priming by motion too rapid to be consciously seen.
AB  - When a rapidly rotating ring of dots was briefly flashed, observers saw only a
      solid ring with no discriminable rotation. However, when this stimulus served as
      a prime that was followed by a target that consisted of a clearly rotating ring
      of dots, response times (RTs) to report the target's rotation were shorter when
      the prime and target directions were congruent than when they were incongruent.
      In accord with shape priming data, this priming effect increased monotonically
      with the prime-target stimulus-onset asynchrony (SOA). The prime also biased the
      perceived direction of an ambiguous apparent motion target, but only at an
      intermediate SOA. At the same SOA, we also found that target presentations
      enabled above-chance discrimination of prime's rotation direction. These outcomes
      demonstrate the processing of motion direction information that is not
      phenomenally represented. They suggest a common mechanism may mediate the priming
      of RTs by shape and motion, whereas a different mechanism mediates perceptual
      measures of motion priming.

PMID- 18078230
TI  - Auditory-visual contextual cuing effect.
AB  - Under incidental learning conditions, a spatial layout can be acquired implicitly
      and facilitate visual searches (the contextual cuing effect). Whereas previous
      studies have shown a cuing effect in the visual domain, the present study
      examined whether a contextual cuing effect could develop from association between
      auditory events and visual target locations (Experiments 1 and 2). In the
      training phase, participants searched for a T among Ls, preceded by 2 sec of
      auditory stimulus. The target location could be predicted from the preceding
      auditory stimulus. In the test phase, the auditory-visual association pairings
      were disrupted. The results revealed that a contextual cuing effect occurs by
      auditory-visual association. Participants did not notice the auditory-visual
      association. Experiment 3 explored a boundary condition for the auditory-visual
      contextual cuing effect. These results suggest that visual attention can be
      guided implicitly by crossmodal association, and they extend the idea that the
      visual system is sensitive to all kinds of statistical consistency.

PMID- 18078231
TI  - Conjunction benefits and costs reveal decision priming for first-order and second
      order features.
AB  - Across two experiments, decision priming was examined for conjunctions composed
      of first-order or first- and second-order stimulus features. Observers indicated
      the presence or absence of one or two features in a Gabor stimulus. When a pair
      of stimulus features differed in their speed of discrimination, responses
      indicating the presence of a conjunction were faster than those for the single
      feature for which discrimination was slowest (conjunction benefits). Also,
      responses indicating the absence of a conjunction were delayed if one of the
      features was present (conjunction costs). These results show that first- and
      second-order features can prime decisions about the presence of a conjunction and
      suggest that the two kinds of signals can be combined at a decision stage after
      the discrimination of stimulus properties has begun for each system.

PMID- 18078232
TI  - Attention effects during visual short-term memory maintenance: protection or
      prioritization?
AB  - Interactions between visual attention and visual short-term memory (VSTM) play a
      central role in cognitive processing. For example, attention can assist in
      selectively encoding items into visual memory. Attention appears to be able to
      influence items already stored in visual memory, as well; cues that appear long
      after the presentation of an array of objects can affect memory for those objects
      (Griffin & Nobre, 2003). In five experiments, we distinguished two possible
      mechanisms for the effects of cues on items currently stored in VSTM. A
      protection account proposes that attention protects the cued item from becoming
      degraded during the retention interval. By contrast, aprioritization account
      suggests that attention increases a cued item's priority during the comparison
      process that occurs when memory is tested. The results of the experiments were
      consistent with the first of these possibilities, suggesting that attention can
      serve to protect VSTM representations while they are being maintained.

PMID- 18078233
TI  - Object- and direction-specific interference between manual and mental rotation.
AB  - We conducted a series of psychophysical experiments to investigate the nature and
      specificity of behavioral interference between mental and manual rotation.
      Participants were asked to mentally rotate five different types of visual stimuli
      -hands, faces, tools, cubes, and natural objects--either clockwise or
      counterclockwise while they simultaneously manually rotated a wheel in the
      concordant or discordant direction. Our study clearly revealed object-specific
      interference between manual and mental rotation. In comparison with a neutral
      baseline condition without any manual rotation, both manual rotation directions
      generally impaired the mental rotation of cubes. In contrast, the mental rotation
      of hands was impaired only by discordant manual rotation. This object- and
      direction-specific interference between manual and mental rotation proved to be
      independent of task difficulty. We furthermore found an angular distance effect
      across different stimulus types.

PMID- 18078234
TI  - Influence of a tone's tonal function on temporal change detection.
AB  - Music cognition research has provided evidence that the tonal function of a
      musical event influences perception and memory. Our study investigated whether
      tonal function influences a basic temporal judgment, notably the detection of a
      temporal change disrupting a sequence's regularity. The sequences consisted of
      six musical events presented in isochrony (or with the fifth event occurring
      earlier or later): Three chords (instilling a tonal context) were followed by a
      tone (repeated three times). The tones fulfilled one of two tonal functions in
      the tonal context. Participants had to detect whether the sequence contained a
      temporal change and were not informed about tonal manipulations. Discrimination
      performance (as measured by d') showed an influence of tonal function on temporal
      change detection: Performance was better for the tonic tone (having the most
      important tonal function in the key) than for the unstable leading tone, the less
      stable mediant tone, and even than the stable dominant tone. The outcome shows
      the influence of listeners' tonal knowledge on a perceptual time judgment and
      suggests that processing of tonal and temporal structures interact at some stage
      of processing.

PMID- 18078235
TI  - Heart, aorta, peripheral and supra aortic trunks imaging realized by MSCT 64. Our
      experience.
AB  - A new generation of Multislice Computed Tomography (MSCT 64) was introduced by
      Siemens in Italy in the end of 2004. It acquires 64 slices per rotation and
      provides significantly improved image quality with drastically reduced scan
      times. This technique allows newer applications, particularly in vascular,
      cardiac, and colonic imaging. We investigated the accuracy of MSCT 64 in 120
      patients for the detection of high-grade coronary-artery stenoses and occlusions.
      A detailed description of the most intriguing images (big vessels of mediastinum,
      supra aortic trunks, collateral circulation in an aortic pathology, aortic
      fissuration) is reported. MSCT 64 (multislice CT 64) represents an undisputed
      technological evolution of the imaging in the living being. Contrary to
      conventional coronary angiography (CCA), it enables to carry out noninvasive
      angiography in various settings, providing potential diagnostic and prognostic
      applications.

PMID- 18078236
TI  - PCNA immunoreactivity revealing normal proliferative activity in the brain of an
      adult Elasmobranch, Torpedo marmorata.
AB  - The brain of adult heterothermic vertebrates can be already provided of quiescent
      cells, scattered ("matrix cells") and/or clustered ("matrix areas"). These
      typical cells, in some regions located at or near ventricular surfaces and at
      peri-ependymal layers, in other territories populating their framework, maintain
      some embryonic properties and are responsible of normal or variously
      experimentally induced proliferative activities. On these topics there are a
      great number of reports concerning Teleostean Osteichthyes, Urodele and Anuran
      Amphibians, Lacertilian Reptiles. At the contrary, only few are the contributions
      regarding the Petromyzontidae. Involving an immunocytochemical marker, the
      Proliferating Cell Nuclear Antigen (PCNA), revealing proliferative events, in the
      last years we have undertaken a reappraisal focused on these encephalic
      performances in normal adult poikilothermal vertebrates. To provide a valid
      comparison between our results and the literature data, our choice of the
      specimens was based on the desire to employ organisms belonging to the same or
      phylogenetically close species used by previous Authors in similar studies. In
      our immunocytochemical panorama there is a substantial agreement between our
      contributions and bibliographic references concerning natural encephalic
      proliferative phenomena in these vertebrates. At this point of our study, the
      last missing piece was represented by the Chondrichthyes about which the
      literature data are lacking. In order to fill this gap, the aim of the present
      research is to investigate, involving the same PCNA test, whether proliferative
      events also persist in the brain of adult cartilaginous fishes. The
      immunostaining images obtained in the Elasmo branch Torpedo marmorata, well-known
      for the emission of high electrical discharges, exhibit undifferentiated cells in
      relationship with the ependymal epithelium lining the cavities of all cerebral
      districts; some other neuroblasts are scattered in the mesencephalic, cerebellar
      and medullar sub-ependymal layers and are found in great number in the thickness
      of the cerebellum. In our re-examination, the present approach, concerning the
      Torpedo marmorata, complete the puzzle. The evidences of these proliferative
      signals are weighed and in an overall view the panorama, which has taken shape
      from our investigations, is illustrated and comparatively discussed.

PMID- 18078237
TI  - Peripheral nerve injury induced expression of mRNA for serine protease inhibitor
      3 in the rat facial and hypoglossal nuclei but not in the spinal cord.
AB  - The current work has documented the expression of the mRNAs for serine protease
      inhibitor 3 (SPI-3) in the facial and hypoglossal nuclei following peripheral
      nerve transection by using the in situ hybridization method. The signals appeared
      6 hour after nerve injury; they became stronger on day 1 of injury and persisted
      for 21 days. SPI-3 may be involved during early events of modulating the
      activities of serine proteases following nerve injury. Such activities may
      include synaptic stripping and re-organization and facilitation of glial cell
      reaction to nerve injury. In the later stages of nerve injury SPI-3 may enhance
      neuronal survival, growth of neurites and re-establishment of synaptic contacts
      in the facial and hypoglossal nuclei. Hypoglossal but not facial nerve
      transection caused the expression of mRNAs for SPI-3 in the pineal gland. The
      signals appeared 6 hours after nerve injury and persisted for 21 days. The
      significance of this observation is not known but it indicates that the pineal
      gland senses injury to some peripheral nerves including the hypoglossal nerve.
      The study has also showed that axotomy of the sciatic nerve did not give rise to
      the up-regulation of the mRNAs for SPI-3 in the spinal cord. There was no
      hybridization signals in the lumbar segments; an indication that SPI-3 may not
      form part of molecules that are released during sciatic nerve transaction by the
      neural and non-neural cells of the spinal cord. At the moment there are no
      antibodies for SPI-3 and therefore future studies are needed to verify the
      findings. It will be interesting also to study on the role of pineal gland during
      peripheral nerve injuries.

PMID- 18078238
TI  - Position, shape and direction of opening of the mental foramen in dry mandibles
      of Tanzanian adult black males.
AB  - This study was aimed at documenting the location, shape, and direction of the
      opening of the mental foramen in dry mandibles of adult black Tanzanian
      population. A hundred mandibles were available for studying. In 45% the mental
      foramen was located below the apex of the second premolar, 35% between the second
      premolar and the first molar, 12% between the first premolar and second premolar
      and 8% below the first molar. The mental foramen was asymmetrically located
      between the right and left sides in 78% of the mandibles. The shape of the mental
      foramen was oval in 54% and rounded in 46% of the mandibles observed. The
      direction of opening was superiorly in 44%, posterosuperiorly in 40%, labially in
      10%, mesially (anteriorly) in 3%, and posteriorly in 3%. Unilateral double mental
      foramen was observed in 3% of the mandibles. In conclusion these results showed
      that the mental foramen in the dry mandibles of adult black male Tanzanians was
      located mostly below the apices of the second premolar or more posteriorly (80%)
      while only a small percentage was located between the first andsecond premolars.
      This is different from previous reports. In more than half the shape was oval and
      it was rounded in less than half of the mandibles. The opening was mainly
      superiorly and posterosuperiorly, with a small percentage opening labially,
      mesially (anteriorly) and posteriorly.

PMID- 18078239
TI  - Unique cellular structures in the parotid gland of an Old world fruit bat,
      Pteropus lylei (Lyle's flying fox).
AB  - Pteropus lylei (Lyle's flying fox), an Old World fruit bat, consumes only ripe
      fruit, which contains low protein and sodium. The carpophagous diet of P. lylei
      presents an adaptive challenge for salivary glands to conserve sufficient
      nutrition for living. Therefore, the parotid glands in both sexes were
      investigated by using light microscopy and transmission electron microscopy. No
      structural difference was observed in the parotid glands between sexes. The
      acinar cell contained dense serous secretory granules, prominent luminal
      microvilli and intercellular canaliculi. The intercalated duct exhibited simple
      cuboidal epithelium with no secretory granule. Striated duct consisted of simple
      columnar epithelium with basal striation, numerous elongated mitochondria, and
      apical vesicles. In the interlobular duct, simple tall columnar epithelium and
      apocrine secretion were found. The interlobar and excretory ducts surprisingly
      contained continuous capillaries that intervened in stratified cuboidal
      epithelium. In addition, there were several blood vessels around the
      interlobular, interlobar and excretory ducts. The morphological adaptation of the
      parotid gland observed in P. lylei enables this species to obtain sufficient
      nutrients from the preferred consumption of ripe fruit. Serous secretory granule
      was suitable for digestion of ripe fruit. A well-developed striated duct,
      continuous capillaries among the epithelial cells of interlobar and excretory
      ducts, and numerous blood vessels around these ducts enhanced the reabsorption of
      amino acids and ions. Structural variations in the parotid gland can indicate not
      only a correlation to diet and survival but also a close relationship of the Old
      World fruit bat to other kinds of bats.

PMID- 18078240
TI  - Presence of erythrocytes in the villous trophoblast cell layer of normal first
      trimester and term human placentae.
AB  - Light and electron microscopic examination of first-trimester and term human
      placental tissues were performed to identify erythrocytes containing hemoglobin
      in the villous trophoblast cell layer. Erythrocytes were not identified in
      chorionic villous epithelium at week 7 of gestation. These cells first appeared
      in the villous cytotrophoblast at week 8, and continued to be present in the
      villous cytotrophoblast until week 9, as shown by benzidine staining. At week 12
      gestation, a cluster of erythrocytes was present in a villous syncytial sprout.
      At 40 and 41 weeks gestation, erythrocytes were located in the villous
      cytotrophoblast cell layer. Electron microscopic observations focused on the
      cytoplasm of villous cytotrophoblast at week 8, the syncytial sprout at week 12
      and the cytotrophoblast cell layer at term, confirmed the presence of
      erythrocytes at an extravascular location, as observed by light microscopy.

PMID- 18078241
TI  - OIG's hammer.

PMID- 18078242
TI  - Pandemic influenza: still a threat.

PMID- 18078243
TI  - Pandemic influenza: a primer.
AB  - Influenza maintains a special position in human medicine as the cause of the
      greatest pandemic of disease in all of human history as well as a continuous and
      significant source of worldwide morbidity and mortality every year. The very
      nature of the influenza virus allows it to evade and adapt to the human
      population. We currently have useful tools such as vaccination and antiviral
      medications to limit this burden; however, appropriate vaccines take time to
      prepare, and antiviral drug resistance has emerged as a significant problem.
      Continued vigilance and pandemic planning are essential, given the continued
      threat of novel strains that can arise and rapidly cause disease across the
      world.

PMID- 18078244
TI  - Pre-hospital pandemic influenza triage.

PMID- 18078245
TI  - Practical challenges in a hospital pandemic influenza preparedness plan.

PMID- 18078246
TI  - The role of nonpharmaceutical interventions during a pandemic.

PMID- 18078247
TI  - Pandemic planning for office-based practices.

PMID- 18078248
TI  - Pandemic influenza planning in Texas: the pediatric perspective.

PMID- 18078249
TI  - Commentary: DSHS plans for an influenza pandemic.

PMID- 18078250
TI  - The many faces of psychiatric education.

PMID- 18078251
TI  - Teaching psychotherapy to psychiatric residents in Israel.
AB  - This work examines the rationale for, and the feasibility of teaching
      psychotherapy to psychiatric residents, and the "what if" of dropping it from the
      curriculum. Psychotherapy is one of the pillars of psychiatry. However, current
      economic constraints and the increasing weight of phenomenological and biological
      psychiatry make it more difficult to prioritize and allocate resources to its
      teaching. The term psychotherapy encompasses several techniques, some of which
      are extremely effective. It often confounds skills, attitudes, theory, body of
      knowledge and specific practices. Looking at each component separately, a stepped
      curriculum for teaching is outlined; alternatives to traditional theories are
      offered; and the need to allocate time and resources for teaching and learning
      are shown as the rate-limiting factor for the survival of psychotherapy within
      psychiatry. Not limited to residents, the debate about psychotherapy in
      psychiatry concerns the profession's core identity and its traditional person
      centered nature.

PMID- 18078252
TI  - Issues of spirituality and religion in psychotherapy supervision.
AB  - OBJECTIVE: We note gaps between the basic science of psychotherapy and the
      spiritual dimensions of religious life; between the beliefs and practices of
      patients and those of therapists; and between evidence for the influence of
      spirituality on health and the lack of its integration into psychotherapeutic
      training. We attempt to provide a framework to bridge this gap in supervision.
      METHOD: We reviewed the literature on the roles of spirituality and religion in
      mental health and illness; on the place of religion in psychotherapy; and on the
      pedagogy of spirituality. RESULTS: Issues requiring attention include definitions
      of terms; awareness of personal beliefs; consideration of the boundaries between
      religiosity and pathology; and distinction between religious structures and
      personal beliefs. A format for addressing these issues in supervision includes:
      assisting the trainee with self-awareness; providing tools for spiritual
      assessment of the patient; providing developmental schema for spirituality; and
      maintaining awareness of the intersubjectivity of the patient-therapist field and
      the trainee-supervisor field. CONCLUSIONS: Existing literature provides usable
      frameworks for integrating religion and spirituality into psychotherapy
      supervision. We offer suggestions on how this may be accomplished.

PMID- 18078253
TI  - Points to ponder regarding contemporary psychiatric training in Israel.
AB  - In an era in which neuroscience is developing rapidly and different
      psychotherapeutic modalities are proliferating, psychiatric training encounters
      new difficulties. This article raises various issues that the authors feel are
      not adequately addressed in contemporary psychiatric residency programs in
      Israel. These include basic issues of doctor-patient relationship; different
      cultural trends such as the increase in popularity of CAM (complementary and
      alternative medicine), the increase in substance abuse, and the increasing
      popularity of different spiritual movements; transcultural aspects affecting the
      prevalence and understanding of different psychopathologies in various sectors of
      the population; ethical issues particular to psychiatric research; and the future
      psychiatrist's role as communicator and educator of GPs, mental health workers
      and the general public. In a time characterized by an abundance of models and
      theories in psychiatry, the authors stress the need to assist residents in
      integrating various theories and models into a comprehensive outlook regarding
      the psyche and psychiatric disorders. As mental hospitals vary greatly in their
      general psychiatric outlook, emphases, and competence of the senior staff in
      different fields and treatment modalities, the authors see programs for
      continuing medical education (CME) as the natural arena in which the issues
      mentioned in this paper should be addressed.

PMID- 18078254
TI  - Changes in the attitudes of Israeli students at the Hebrew University Medical
      School toward residency in psychiatry: a cohort study.
AB  - INTRODUCTION: Recruitment of medical students to the field of psychiatry has been
      on the decline in the western world over the last decades. Trends in students'
      interest in psychiatry is a topic of research studied by medical educators in
      many countries. Our aim was to examine changes in the attitudes of Israeli
      medical students toward different specialties, including psychiatry, over the
      course of their training. We attempted to identify trends and patterns in these
      perceptions. METHOD: A standard validated 26-item questionnaire was administered
      to 307 medical students during their clinical years at the Hebrew University
      Medical School in 2003-2004. The response rate of the current survey was 69%. The
      questionnaire evaluated medical students' opinions and perceptions towards
      psychiatry, compared with other medical specialties. The results were compared
      with those found by Abramowitz and Gofrit in 2005 dealing with the same student
      population during their preclinical studies in 2000-2002. RESULTS: Psychiatry was
      ranked as the least attractive specialty by the whole population of students in
      their clinical years (4th-6th year) with an average of 14.9% of students
      regarding psychiatry as a possible career option; 32.8% of the same cohort
      considered psychiatry as a specialty during the preclinical years in medical
      school. Significantly, psychiatry's attractiveness was rated the lowest in many
      aspects, and most attractive in lifestyle. These opinions showed a marked
      deterioration from those expressed by the same cohort during the preclinical
      years. DISCUSSION: Attitudes toward psychiatry at the start of medical school are
      positive. Thus the potential for recruitment of future psychiatrists among the
      students is good. However, the present study showed a marked negative change in
      medical students' perceptions towards psychiatry as a possible career choice
      during their training. The problematic image of psychiatry as a profession has
      been documented in several countries. Our findings are similar. In addition, we
      identify the decline in interest in selecting psychiatry as a possible residency
      as occurring during the clinical training years. Programs should be targeted to
      those who show initial curiosity and interest in the workings of the mind and
      spirit.

PMID- 18078255
TI  - The attitude of medical students to psychiatric patients and their disorders and
      the influence of psychiatric study placements in bringing about changes in
      attitude.
AB  - The aim of this study was to determine the general attitude of final year medical
      students towards psychiatric patients and psychiatric disorders and to reveal the
      influence of psychiatric study experience in changing the behavior and perception
      of students. The study comprised 172 final year medical students undergoing a
      period of placement at the Ondokuz Mayis University Medical School Department of
      Psychiatry who agreed to participate. They were asked to fill in the Opinions
      about Mental Illness Ideology Scale (OMI) the day before they commenced, on the
      last day of their placement and three months after completing it. The students
      reported the highest and lowest scores from the benevolence and social
      restrictiveness sub-dimensions of the OMI, respectively. The mean
      authoritarianism score was significantly higher in males than in females. The
      means of the OMI scores obtained over the three different periods were not
      statistically different. Medical school psychiatry departments need to develop
      new curricula to convey scientific information to students and play a pivotal
      role in developing, implementing and evaluating suitable programs leading to
      appropriate attitude development.

PMID- 18078256
TI  - The examination as ritual.

PMID- 18078257
TI  - Professional integration and re-education for immigrant psychiatrists: a personal
      perspective "docendo distimus".
AB  - To be a good psychiatrist, aside from being knowledgeable, one must acknowledge
      and be constantly aware of the importance of ethnic customs and cultural
      differences. Psychiatrists who emigrated from the former Soviet Union to Israel,
      who were raised and educated in totalitarian systems, must develop the
      flexibility necessary to disengage from preconceptions and learn to flourish in a
      democratic society. The acculturation process is mutual, and native Israelis need
      to acquaint themselves with all aspects of Russian history and culture, in order
      to bond with their immigrant colleagues. At the same time, ethnic sensitivity and
      sincere involvement in all aspects of Israeli culture are crucial for the
      immigrant's development of a sense of security in the psychiatric profession and
      for developing the rapport necessary for treating native Israelis.

PMID- 18078258
TI  - Education and postgraduate education of psychiatrists in the Soviet Union and
      their integration into a new milieu. A view from the present to the past of
      former Soviet psychiatrists.
AB  - The article presents the problems and difficulties that psychiatrists from the
      former Soviet Union (FSU) have to cope with in Israel. Immigration and
      acculturation in a new milieu is a complex process and even more complicated for
      those whose specialty is medicine and particularly psychiatry. There is a wide
      gap between the skills and knowledge that new immigrants brought with them from
      the FSU and the professional demands in the new country. Psychiatry and
      psychiatric education in the FSU were determined by the cultural practices and
      traditions of the region and the organizational principles of the USSR which were
      very different than those of western society and the State of Israel. In
      comparison to the West, postgraduate psychiatric training in the USSR was shorter
      and less rigorous with an emphasis on biological therapy. Soviet "psychotherapy"
      was more reality oriented and more authoritarian than in the West, stressing
      "collective" group therapy. We describe the basic principles of Soviet medical
      education and the radically different social, intellectual and political history
      of the former Soviet Union. We relate the experiences of psychiatrists in the FSU
      in learning dynamic psychotherapy and the difficulties connected with this
      education. Moreover, the process of educating psychiatric residents is described
      from a supervisor's point of view. This complex process led to some major
      difficulties. In order to cope with the difficulties the supervisor employed a
      broad variety of means and techniques: an introductory course and a basic seminar
      about fundamental cornerstones of psychotherapy were offered.

PMID- 18078259
TI  - Attitudes of Israeli primary care physicians towards mental health care.
AB  - Rates of depression and anxiety are increasing all over the world in developed
      and developing countries as well and Israel is no exception to this trend. People
      suffering from depression and anxiety disorders tend not to turn for professional
      help to mental health clinics but to primary care. This cross-sectional study
      examines the attitudes and barriers of primary care physicians in the southern
      region of Israel toward providing care for depression and anxiety in their
      practices. In 2002 we sent a questionnaire concerning attitudes and barriers
      toward depression and anxiety to 99 primary care physicians from 14 primary care
      clinics with a response rate of 67.7% (67 physicians); 80.6% of the participants
      agreed with the statement that depression and anxiety are frequent problems in
      primary care and they should be treated in primary care clinics, but 37.3%
      reported to have little interest in treating mental disorders, 47.7% thought
      depression and anxiety should be treated in mental health clinics; 43.3% of the
      participants declared that they experienced a personal difficulty in taking care
      of patients with depression and anxiety, and 85% identified time constraint as a
      major barrier to care of depression and anxiety in primary care. This study
      suggests that in order to improve treatment of depression and anxiety in primary
      care, there is a need for a change of attitudes of the primary care providers.

PMID- 18078260
TI  - Psychiatric inpatient and staff attitudes regarding smoking reduction.
AB  - AIMS: We assessed the interest of psychiatric inpatients and the staff in a
      smoking reduction program. METHODS: Inpatients, nurses, social workers and
      psychologists at a university-affiliated psychiatric hospital completed
      questionnaires addressing attitudes towards smoking and the desire to reduce
      smoking. RESULTS: 52% of the inpatients (N = 160) and 37.3% of the staff members
      (N = 41) reported that they smoked. Mean number of cigarettes for patients was
      21.4 cigarettes per day for men, and 18.8 for women; 74 patients (46.2% of the
      smokers) and 96 staff members (88% of the smokers) expressed interest in
      participating in a smoking reduction program. No correlation was found between
      the rate of smoking among the staff and the rate of smoking of the patients in
      any given department. CONCLUSIONS: Psychiatric inpatients and their caregivers
      who smoke are interested in reducing the number of cigarettes that they smoke.
      Further study regarding the initiation of therapeutic smoking reduction programs
      in inpatient settings is warranted.

PMID- 18078261
TI  - Treatment lag on the way to the mental health clinic among Arab- and Jewish
      Israeli patients.
AB  - BACKGROUND: The early recognition and timely treatment of psychiatric disorders
      helps reduce suffering, prevents mental disabilities and makes interventions more
      cost-effective. OBJECTIVE: To examine treatment lag among Arab- and Jewish
      Israelis applying to psychiatric clinics for the first time, and the association
      of this lag with selected socio-demographic and mental health-related variables.
      METHODS: 251 adult outpatients making their first-ever visit to a psychiatric
      clinic completed a self-administered questionnaire, including questions on the
      time elapsed since the onset of the current disorder, reasons for the treatment
      lag, source of referral, main complaints, current psychiatric problems (self
      diagnosis), attitudes to psychiatric disorders and treatment, pathways to care,
      and standard sociodemographic information. Univariate and multivariate analyses
      were performed to compare Arab- and Jewish-Israelis on parameters of interest.
      RESULTS: Compared with their Jewish counterparts, Arab-Israeli patients showed a
      two-fold delay in initial treatment contact (X2 = 4.00, df = 1, p < 0.05).
      Logistic regression analysis showed that this delay was associated with lower
      schooling, other-than-psychiatric attribution of mental symptoms, and a more
      pessimistic attitude to the successful treatment of mental disorders in general
      and for oneself in particular. CONCLUSIONS: Since longer treatment delay was
      mostly associated with potentially modifiable knowledge and attitudes on mental
      disorders and treatment, educational programs targeting specific community
      sectors and community agents should be promoted to shorten this lag.

PMID- 18078262
TI  - Brain metastases: epidemiology and pathophysiology.

PMID- 18078263
TI  - The economics of brain metastases.

PMID- 18078264
TI  - Neuroimaging of parenchymal brain metastases.

PMID- 18078265
TI  - Symptom management and supportive care of the patient with brain metastases.
AB  - The focus of care for patients with brain metastases will always be on
      therapeutic options such as surgery, radiotherapy, and chemotherapy. However,
      proper symptom management and supportive care of non-therapeutic issues will be
      equally as important, including treatment of seizures, use of anticonvulsants,
      corticosteroids, and gastric acid inhibitors, assessment of swallowing
      dysfunction, treatment of thromboembolic events, appropriate use, and safe
      application of anticoagulation, and evaluation of psychiatric issues. Appropriate
      management of these supportive aspects of patient care will improve overall
      quality of life and allow the patient and family to more easily concentrate on
      treatment.

PMID- 18078266
TI  - Surgery for brain metastases.

PMID- 18078267
TI  - Radiation for brain metastases.

PMID- 18078268
TI  - Dural and skull base metastases.

PMID- 18078269
TI  - Pediatric brain metastasis from extraneural malignancies: a review.

PMID- 18078270
TI  - Brain metastases in hematologic malignancies.

PMID- 18078271
TI  - Chemotherapy for brain metastases: breast, gynecologic and non-melanoma skin
      malignancies.

PMID- 18078272
TI  - Chemotherapy for brain metastases due to lung cancer and melanoma.

PMID- 18078273
TI  - Palliative care for patients with brain metastases.

PMID- 18078274
TI  - [The outcome of recurrent patellar dislocation treatment with the Insall
      procedure].
AB  - The choice of appropriate treatment of recurrent lateral patellar dislocation
      (RPD) is the source of constant debate because of unacceptable treatment
      outcomes. The aim of this study is to assess the outcome of operative treatment
      of RPD with the use of proximal realignment method by Insall. 94 patients (109
      knees), who were present at the final examination, after the average follow-up
      6.8 years, and met the inclusion criteria, were operated with the Insall
      procedure due to RPD. There were 63.3% of excellent and good results and 11% poor
      in the final outcome score. The outcomes of treatment of RPD with the use of
      Insall procedure are comparable with the published outcomes of other procedures.
      It is an important surgical method in treatment in immature patients. The
      advantage of this method is that it does not cause serious complications,
      however, the disadvantage is an unacceptably high rate of recurrent dislocations.

PMID- 18078275
TI  - [Arthroscopic verification of meniscus repair].
AB  - The purpose of this study was to verify the arthroscopic meniscus repair by
      second-look arthroscopy. From November 2001 to October 2005, 28 meniscus (18
      medial and 10 lateral) were repaired in 26 patients (two patients had both
      menisci in one knee repaired). There were 11 females and 15 males. The average
      age at surgery was 25.5 (range, 13 to 52 years of age). The indication for repair
      was a full-thickness, vertical tear > or = 8 mm. Meniscus repair was combined
      with partial meniscectomy of posterior horn because of horizontal tear in 3
      cases. In 1 zone 14 meniscus were injured and in 2 zone--also 14 meniscus,
      according to Cooper's classification. All patients had anterior cruciate ligament
      rupture. The average time interval between the injury and the repair was 22 weeks
      (range, 2 weeks to 2 years). The inside-out suture was used in 18 repairs, all
      inside--3 repairs, outside-in--2 repairs and a mixed technique--5 repairs.
      Arthroscopic evaluation of meniscus repair was performed on average after 15
      weeks (range, 2 months to 37 weeks) since the suture. That was done during the
      second stage of treatment--ACL reconstruction. There were 78.6% of completely
      healed repairs, 10.7% of incompletely healed and 10.7% were not healed.

PMID- 18078276
TI  - [Lower limb dysaesthesia after anterior cruciate ligament reconstructions with
      hamstring tendons. A comparison of vertical versus oblique harvest site
      incisions].
AB  - The purpose of this retrospective study was to compare early lower limb
      dysaesthesia after anterior cruciate ligament (ACL) reconstructions. The
      procedures were performed with ST and GR tendons using vertical or oblique
      harvest site incisions. In the year 2006 52 patients were treated due to total
      ACL rupture. In 35 we performed vertical harvest site incision and in 17 oblique
      incision were performed. Average follow-up was 1 month. At this time patients
      were asked to draw any dysaesthesia area on a knee diagram, if present. In the
      vertical harvest site incision 31 patients had dysaesthesia about the knee, and
      the average dysaesthesia area was 46.8 cm2. In the oblique harvest site incision
      15 patients had dysaesthesia about the knee and the average dysaesthesia area was
      44.3 cm2. The dysaesthesia areas were mostly of ellipse-like shape. There was no
      signigicant difference between two groups.

PMID- 18078277
TI  - [Reability of clinical assesment of injury of intraarticular structures of the
      knee joint verified by arthroscopic examination].
AB  - The aim of this paper is an evaluation of specificity, sensitivity and accuracy
      of clinical examination in intraarticular disorders of the knee joint. Study was
      performed on 100 patients (31 female, 69 male) (age 15-61 years) treated by
      arthroscopy. Our study showed the high sensitivity and specificity in assessment
      of leasions of the medial meniscus and leasions of the anterior cruciate
      ligament. Leasions of the medial meniscus and of the anterior cruciate ligamnet
      one. Leasions of the medialis meniscus may be painless and may not be associated
      with trauma.

PMID- 18078278
TI  - [Results of the treatment of the distal femoral epiphysiolysis].
AB  - INTRODUCTION: Distal femoral epiphysiolysis (DFE) is rare. In most of the cases
      it occures as an open epiphysiolysis. In the past DFE had often resulted in a
      tissue necrosis and required an amputation. Among complications limb shortening
      due to premature epiphyseal closure and deviation of the limb axis are evidenced.
      AIM: This study was conduced in order to evaluate the results of the treatment of
      DFE. MATERIAL: Eight children suffering from DFE who had undergone a treatment
      between 1990 and 2005 were reviewed. The mean age at the time of injury was 15.3
      years. All cases of epiphysiolysis have been classified as Salter-Harris type II.
      The treatment consisted of reduction and 6 weeks immobilisation in 3 cases.
      Reduction followed by K-wire stabilization and immobilisation was applied in all
      other cases. METHODS: The follow-up evaluation covered a clinical and
      roentgenographic examination. The angular deformmity of tibia was measured in
      saggital and frontal plane in comparison to intact side. The range of motion and
      stability of both knee joints were recorded as well. The comparative X-ray
      pictures of the femur and knee joint were taken in A-P and lateral positions.
      RESULTS: The study revealed a premature closure of the injured distal femoral
      epiphysis in four children. There was a limb shortening of over 2 cm in 3 cases
      and over 3cm in one case. CONCLUSION: The distal femoral epiphysiolysis is a rare
      type of injury. It often leads to leg length discrepancy.

PMID- 18078279
TI  - [Long term results of femoral neck fractures in children].
AB  - Femoral neck fractures in children occur most frequently as a result of
      automotive accident or free fall. A long term results in 36 cases of femoral head
      fractures in children age 2-18 (9.8 yrs on average) were evaluated. The fractures
      were divided based on the most widely used Delbet scale: type I--transepiphyseal
      (2 cases), type II--transcervical (8 cases), type III--cervicotrochanteric (14
      cases) and type IV--intertrochanteric (12 cases). The minimum evaluation period
      was 3 years (from 3 up to 29 years). The results were evaluated based on the
      Ratliff criteria. The long term results observed were better in children treated
      with type III and IV fractures than in type I and II. Also cases treated within 3
      days from the trauma had better long term results than cases treated later. The
      significantly better results of femoral head fractures occurring in children
      under 6 yrs of age is most likely connected with the change of the blood supply
      to the proximal femoral region occurring at the age of 4. The most common
      complication was the avascular necrosis of the femoral head (36%).

PMID- 18078280
TI  - [The role of plantar calcaneonavicular ligament complex in the development of the
      adult flat foot--anatomical study].
AB  - Acquired adult flat foot, despite numerous research projects, is a controversial
      clinical entity. Recently the role of plantar calcaneonavicular ligament complex
      (spring ligament) in stabilization of the longitudinal arch of the foot has drawn
      an attention. Since there are differences in anatomical description of his
      complex in the literature, the main aim of our study was to anatomically evaluate
      this complex. Ten cadaver feet were examined. In four cases spring ligament
      complex comprised two components: superomedial calcaneonavicular ligament and
      inferior calcaneonavicular ligament. In six cases complex was composed of three
      ligaments and we were able to identify structure of the third ligament. In this
      subgroup in two cases the spring ligament had its own fibrocartilage surface
      connected by tiny fibrous band with fibrocartilage articular surface. In summary,
      the spring ligament complex comprises superomedial calcaneonavicular ligament and
      inferior calcaneonavicular ligament. In majority of cases one can distinguish
      structure of the third ligament.

PMID- 18078281
TI  - [Quality of life in patients before and after total hip arthroplasty].
AB  - INTRODUCTION: Osteoarthritis is the most common joint disease in adults and
      according to WHO is one of the civilisation threats. Total joint replacement is
      the best method of treatment of severe osteoarthritis. MATERIAL AND METHODS: The
      study group consisted of 62 (44 women, 18 men) patients, who due to the severe
      osteoarthritis underwent total hip replacement at the Department of Orthopaedics
      Poznan University of Medicine. The mean age was 63 (range 30-87). For the
      evaluation of the quality of life the modified questionnaire WHOQOL-100 was used.
      The first evaluation was performed before the surgery, the second one 12-18
      (average 14) months postoperatively. RESULTS: At the final evaluation the
      improvement was observed in the following domains: physical, psychological, level
      of independence, environmental and the global quality of life. No change was
      observed in the domain "social relations". The greatest improvement was observed
      in the following subscales: "pain and discomfort", "vitality and fatigue",
      mobility, "everyday activities", "drug dependence", transportation. No
      significant change was found in the following subscales: "sleep and rest",
      "positive feelings", "ability to work and learn", "personal social relations" and
      accessibility and quality of healthcare.

PMID- 18078282
TI  - [An aggressive chondroblastoma mimicking paraosteal osteosarcoma].
AB  - We present a rare case of an aggressive form of chondroblastoma arising from
      proximal radius. Because of an initial histopathologic diagnosis of paraosteal
      osteosarcoma, the patient was treated with preoperative chemotherapy and
      afterwards a local tumor resection with one half of proximal radius was
      performed. A final histopathologic examination revealed typical benign
      chondroblastoma. We discuss the rare localisation of chondroblastoma and its
      differential diagnosis with surface osteosarcoma.

PMID- 18078283
TI  - [Observation of healing process of operative wound in the first Polish upper limb
      transplant].
AB  - The goal of this paper was to present the healing process of the operative wound
      of the hand transplant. The recipient was a man, 32 years of age who lost his
      right dominant hand 14 years ago, as a result of an accident. The transplant was
      made at the level of the halves of a forearm. The total ischemia time was 10.5
      hrs. The recipient was qualified by a tedious process of preparation, he was
      thoroughly informed about all of the risks involved. The wound was primarily
      closed with loose sutures, without a skin graft. The healing process was
      complicated by creation of a large hematoma, wound dispersal and candida
      infection. The granulation process was very slow. Only traditional dressings were
      applied. The secondary wound closure was performed with a skin graft, the healing
      was ended after 64 days. Within this period neither general infection nor
      rejection symptoms were observed.

PMID- 18078284
TI  - [Isokinetic evaluation of external rotators and abductors of the shoulder before
      and after arthroscopic decompression of suprascapular nerve due to its neuropathy
      -preliminary report].
AB  - The paper presents results of objective isokinetic evaluation of shoulder
      abductors and external rotators peak torque in 4 cases (2 women and 2 men)
      suffering from suprascapular nerve neuropathy (SNN). The mean age of patients was
      25 years. The clinical diagnosis of SSN involvement was confirmed by
      electromyographic study in all cases. The radiological, sonographic and
      additionally magnetic resonas (2 cases operated on) examinations proved the
      absence of bone and soft tissues pathologies (ganglion and rotator cuff). The
      arthroscopic decompression of SSN was done in 2 cases. Isokinetic evaluation (180
      degrees/s) disclosed weakness of shoulder abductors and external rotators in all
      cases and decrease of side to side difference of their peak torque 6 months after
      surgery. The patients operated on refused control EMG evaluation since they
      experience complete pain relief and improvement of function. There were no
      complications. Arthroscopic suprascapular nerve decompression can be done safely
      and effectively in properly selected cases. The isokinetics offers objective pre
      and postoperative evaluation of muscles involved by SNN.

PMID- 18078285
TI  - Revision total hip arthroplasty with cementing technique--five-year results.
AB  - AIM: To investigate the result of cemented revision hip arthroplasty. MATERIAL
      AND METHODS: Twenty-one revision hip arthroplasties for aseptic loosening with
      cementing technique during the period 1990-2002 were followed-up. There were 12
      women and 9 men with mean age at the time of revision 61 years (33 to 76 years).
      The mean follow-up for the group was 5.2 years (range, 2 to 13 years). The
      clinical evaluation was performed with the Harris hip score. Implant survival,
      pain, function and complications were recorded. Plain radiographs were reviewed
      and the hips were graded for osteolysis and loosening. Wear of the polyethylene
      was measured. RESULTS: No component was exchanged. Three of the acetabular and
      three of the stem components in the hips with early cementing technique were
      loose. In two patients three surgeries were performed for trochanteric problems
      and persistent pain. Clinical result and bone defects preoperatively as well as
      wear and osteolysis correlated significantly. DISCUSSION: Stable fixation of the
      prosthesis is of paramount importance in revision surgery. In cases with severe
      bone defects stable interface is difficult to be achieved. This may change stress
      distribution and subsequently lead to loosening. CONCLUSION: Better preoperative
      planning and improvement in cementing technique may improve results. Other
      revision techniques may be considered in cases with severe bone deficiencies.

PMID- 18078286
TI  - Observations on nerves evaluation methods for efficiency analysis of the
      operative treatment in upper extremity compressive neuropathies.
AB  - Authors present the evaluation scales for nerve efficiency for functional
      recovery after operative treatment of compressive neuropathies in the upper limb.
      The methodology consists of both subjective and objective evaluation. Presented
      methods are non invasive and may be performed in every medical examination room.

PMID- 18078287
TI  - Hypoxic fed-batch cultivation of Pichia pastoris increases specific and
      volumetric productivity of recombinant proteins.
AB  - High cell density cultivation of Pichia pastoris has to cope with several
      technical limitations, most importantly the transfer of oxygen. By applying
      hypoxic conditions to chemostat cultivations of P. pastoris expressing an
      antibody Fab fragment under the GAP promoter, a 2.5-fold increase of the specific
      productivity q(P) at low oxygen supply was observed. At the same time the biomass
      decreased and ethanol was produced, indicating a shift from oxidative to
      oxidofermentative conditions. Based on these results we designed a feedback
      control for enhanced productivity in fed batch processes, where the concentration
      of ethanol in the culture was kept constant at approximately 1.0% (vv(-1)) by a
      regulated addition of feed medium. This strategy was tested successfully with
      three different protein producing strains, leading to a three- to sixfold
      increase of the q(P) and threefold reduced fed batch times. Taken together the
      volumetric productivity Q(P) increased 2.3-fold.

PMID- 18078288
TI  - Computer simulations of the energy dissipation rate in a fluorescence-activated
      cell sorter: Implications to cells.
AB  - Fluorescence activated cell sorting, FACS, is a widely used method to sort
      subpopulations of cells to high purities. To achieve relatively high sorting
      speeds, FACS instruments operate by forcing suspended cells to flow in a single
      file line through a laser(s) beam(s). Subsequently, this flow stream breaks up
      into individual drops which can be charged and deflected into multiple collection
      streams. Previous work by Ma et al. (2002) and Mollet et al. (2007; Biotechnol
      Bioeng 98:772-788) indicates that subjecting cells to hydrodynamic forces
      consisting of both high extensional and shear components in micro-channels
      results in significant cell damage. Using the fluid dynamics software FLUENT,
      computer simulations of typical fluid flow through the nozzle of a BD FACSVantage
      indicate that hydrodynamic forces, quantified using the scalar parameter energy
      dissipation rate, are similar in the FACS nozzle to levels reported to create
      significant cell damage in micro-channels. Experimental studies in the
      FACSVantage, operated under the same conditions as the simulations confirmed
      significant cell damage in two cell lines, Chinese Hamster Ovary cells (CHO) and
      THP1, a human acute monocytic leukemia cell line.

PMID- 18078289
TI  - Improved production of recombinant human antithrombin III in Chinese hamster
      ovary cells by ATF4 overexpression.
AB  - To improve the production of recombinant human antithrombin III (AT-III) in
      Chinese hamster ovary (CHO) cells, the genes encoding transcription factors, ATF4
      (activating transcription factor 4) and XBP-1s (the spliced form of X-box binding
      protein 1), which were involved in the mammalian unfolded protein response (UPR),
      were cloned from CHO-K1 cells. Overexpression of ATF4 significantly enhanced the
      production of recombinant AT-III in CHO 13D-35D cells. The specific rate of AT
      III production in the ATF4-overexpressed CHO 13D-35D cells reached approximately
      23 pg/cell/day. After 144 h of incubation, the AT-III concentration in the
      culture supernatant was twofold greater compared to that observed with parental
      CHO 13D-35D cells. In contrast, ectopic expression of XBP-1s failed to enhance
      the production of recombinant AT-III in CHO 13D-35D cells. RT-PCR analysis
      revealed that high levels of XBP-1s mRNA were present in the CHO cells,
      regardless of ectopic expression of XBP-1s. Our results indicate that
      overexpression of the UPR transcription factor ATF4 is a promising means for
      improving the production of secreted protein pharmaceuticals in CHO cells.

PMID- 18078290
TI  - An actively mixed mini-bioreactor for protein production from suspended animal
      cells.
AB  - Biopharmaceutical production would benefit from rapid methods to optimize
      production of therapeutic proteins by screening host cell line/vector
      combination, culture media, and operational parameters such as timing of
      induction. Miniaturized bioreactors are an emerging research area aiming at
      improving the development speed. In this work, a 3 mm thick mini-bioreactor
      including two 12 mm wide culture chambers connected by a 5 mm wide channel is
      described. Active mixing is achieved by pressure shuttling between the two
      chambers. Gas-liquid phase exchange for oxygen and carbon dioxide is realized by
      molecular diffusion through 50 microm thick polymethylpentene membranes. With
      this unique design, a velocity difference between the middle area and the side
      areas at the interfaces of the culture chambers and the connecting channel is
      created, which enhances the mixing efficiency. The observed mixing time is on the
      order of 100 s. The combination of high permeability toward oxygen of
      polymethylpentene membranes and fluid movement during active pressure shuttling
      enables higher volumetric oxygen transfer coefficients, 5.7 +/- 0.4-14.8 +/- 0.6
      h(-1), to be obtained in the mini-bioreactors than the values found in
      traditional 50 mL spinner flasks, 2.0-2.5 h(-1). Meanwhile, the calculated volume
      averaged shear stress, in the range of 10(-2)-10(-1) N/m(2), is within the
      typical tolerable range of animal cells. To demonstrate the applicability of this
      mini-bioreactor to culture suspended animal cells, the insect cell, Spodoptera
      frugiperda, is cultured in mini-bioreactors operated under a K(L)a value of 14.8
      +/- 0.6 h(-1) and compared to the same cells cultured in 50 mL spinner flasks
      operated under a K(L)a value of 2.2 h(-1). Sf-21 cells cultured in the mini
      bioreactors present comparable length of lag phases and growth rates to their
      counterparts cultured in 50 mL spinner flasks, but achieve a higher maximum cell
      density of 5.3 +/- 0.9 x 10(6) cell/mL than the value of 3.4 +/- 0.4 x 10(6)
      cell/mL obtained by cells cultured in 50 mL spinner flasks. Sf-21 cells infected
      with SEAP-baculovirus produce a maximum SEAP concentration of 11.3 +/- 0.7 U/mL
      when cultured in the mini-bioreactor. In contrast, infected Sf-21 cells cultured
      in 50 mL spinner flasks produce a maximum SEAP concentration of 7.4 +/- 0.9 U/mL
      and onset of production is delayed from 18 h in minibioreactor to 40 h in spinner
      flasks.

PMID- 18078291
TI  - Biosilicification of dual-fusion enzyme immobilized on magnetic nanoparticle.
AB  - Rapid recovery, immobilization, and silica encapsulation of a dual-fusion enzyme
      was achieved by using iminodiacetic acid (IDA) modified magnetic nanoparticle as
      a carrier. D-amino acid oxidase (DAAO) of Rhodosporidium toruloides was used as a
      model enzyme in which a silica-precipitating peptide R5 and a metal ion
      complexing peptide (His)(6) were fused to its N- and C-terminal, respectively.
      After charging the magnetic particle with Cu(2+), the dual-fusion DAAO of 0.43 g
      could be directly recovered from the recombinant E. coli crude extract and
      immobilized on 1 g of the magnetic particle. Once in contact with hydrolyzed
      tetramethoxysilane (TMOS), the homogeneously dispersed immobilized dual-fusion
      DAAO was biosilicificated to form aggregates with size about 50 microm. The
      silica-encapsulated immobilized DAAO demonstrated a pyruvic acid production rate
      comparable with that of the naked immobilized DAAO in five repeated batch
      reactions when D-alanine was used as substrate. Furthermore, 85% of its activity
      remained after incubation at 60 degrees C for 1 h while the naked immobilized
      DAAO lost all its activity. This process provides the advantages that recombinant
      fusion enzyme can be directly recovered from crude extract, silica encapsulation
      protects the enzyme from leakage and denaturation, and the enzyme activity can be
      easily retrieved by applying a magnetic field.

PMID- 18078292
TI  - Case study and application of process analytical technology (PAT) towards
      bioprocessing: use of on-line high-performance liquid chromatography (HPLC) for
      making real-time pooling decisions for process chromatography.
AB  - Process analytical technology (PAT) has been gaining a lot of momentum in the
      biopharmaceutical community due to the potential for continuous real time quality
      assurance resulting in improved operational control and compliance. This paper
      presents a PAT application for one of the most commonly used unit operation in
      bioprocessing, namely liquid chromatography. Feasibility of using a commercially
      available online-high performance liquid chromatography (HPLC) system for real
      time pooling of process chromatography column is examined. Further, experimental
      data from the feasibility studies are modeled and predictions of the model are
      compared to actual experimental data. It is found that indeed for the application
      under consideration, the online-HPLC offers a feasible approach for analysis that
      can facilitate real-time decisions for column pooling based on product quality
      attributes. It is shown that implementing this analytical scheme allows us to
      meet two of the key goals that have been outlined for PAT, that is, "variability
      is managed by the process" and "product quality attributes can be accurately and
      reliably predicted over the design space established for materials used, process
      parameters, manufacturing, environmental, and other conditions." Finally, the
      implications of implementing such a PAT application in a manufacturing
      environment are discussed. The application presented here can be extended to
      other modes of process chromatography and/or HPLC analysis.

PMID- 18078293
TI  - Controlling the membrane fluidity of yeasts during coupled thermal and osmotic
      treatments.
AB  - Yeasts are often exposed to variations in osmotic pressure in their natural
      environments or in their substrates when used in fermentation industries. Such
      changes may lead to cell death or activity loss. Previous work by our team has
      allowed us to relate the mortality of cells exposed to a combination of thermal
      and osmotic treatments to leakage of cellular components through an unstable
      membrane when lipid phase transition occurs. In this study, yeast viability was
      measured after numerous osmotic and thermal treatments. In addition, the fluidity
      of yeast membranes was assessed according to a(w) and temperature by means of 1,6
      diphenyl-1,3,5-hexatriene (DPH) anisotropy measurement. The results show that
      there is a negative correlation between the overall fluidity variation undergone
      by membranes during treatments and yeast survival. Using a diagram of membrane
      fluidity according to a(w) and temperature, we defined dehydration and
      rehydration methods that minimize fluidity fluctuations, permitting significantly
      increased yeast survival. Thus, such membrane fluidity diagram should be a
      potential tool for controlling membrane state during dehydration and rehydration
      and improve yeast survival. Overall fluidity measurements should now be completed
      by accurate structural analysis of membranes to better understand the plasma
      membrane changes occurring during dehydration and rehydration.

PMID- 18078294
TI  - Medium factor optimization and fermentation kinetics for phenazine-1-carboxylic
      acid production by Pseudomonas sp. M18G.
AB  - We investigated the production of biofungicide phenazine-1-carboxlic (PCA) by
      Pseudomonas sp. M18G, a gacA-deficient mutant of M18 for PCA high-production.
      Glucose was chosen as the optimal carbon source and soy peptone as the nitrogen
      source. A Plackett-Burman design revealed that glucose, soy peptone and NaCl were
      the most significant factors in PCA fermentation. Response surface methodology
      (RSM) and artificial neural network (ANN) models involving the significant
      factors were developed using common data. The prediction accuracy of ANN was
      slightly higher compared to RSM. The genetic algorithm (GA) was used to search
      the optimal input space of the trained ANN model and find the corresponding PCA
      yield. The optimum composition was found to be: glucose 34.3 g L(-1), soy peptone
      43.2 g L(-1), NaCl 5.7 g L(-1), and the predictive maximum PCA yield reached
      980.1 microg mL(-1). The optimized medium allowed PCA yield to be increased from
      673.3 to 966.7 microg mL(-1) after verification experiment tests. Additionally,
      PCA fermentation kinetics was investigated. Kinetic models based on the modified
      Logistic and Luedeking-Piret equations were developed, providing a good
      description of temporal variations of biomass (X), product (P), and substrate (S)
      in PCA fermentation.

PMID- 18078295
TI  - Transcriptional regulation of changes in growth, cell cycle, and gene expression
      of Saccharomyces cerevisiae due to changes in buoyancy.
AB  - To understand the cellular effects of magnetic traps requires independent
      analysis of the effects of magnetic field, gravity, and buoyancy. In the current
      study, buoyancy is manipulated by addition of Ficoll, a viscous substance that
      can create gradients of buoyancy without significantly affecting osmolality.
      Specifically, we investigated whether Ficoll induces concentration dependent
      changes in cell growth, cell cycle, and gene expression in Saccharomyces
      cerevisiae, with special attention paid to the neutrally buoyant concentration of
      35% Ficoll. Cell growth and cell cycle analysis were examined in three strains:
      wild-type (WT) yeast and strains with deletions in transcription factors Msn4
      (Msn4Delta) or Sfp1 (Sfp1Delta). Changes in growth were observed in all three
      strains with WT and Msn4Delta strains showing strong concentration dependence. In
      addition, these changes in growth were supported by changes in the cell cycle of
      all three strains. Gene expression changes were observed in seven GFP-reporter
      strains including: SSA4, YIL052C, YST2, Msn4DeltaSSA4, Sfp1DeltaSSA4,
      Msn4DeltaYIL052C, and Sfp1DeltaYIL052C. Buoyancy forces had selective
      concentration dependent effects on gene expression of SSA4 and YIL052C with
      transcription factor dependence on Msn4. Additionally, SSA4 expression was
      dependent on Sfp1. YST2 gene expression was not dependent on changes in buoyancy
      force. This study shows that buoyancy has selective and concentration dependent
      effects on growth, cell cycle and gene expression, some of which are Msn4 and
      Sfp1 dependent. For the first time, SSA4 gene expression is shown to be dependent
      on Sfp1 and YIL052C gene expression is dependent on Msn4.

PMID- 18078296
TI  - Creating a spectrum of fibrocartilages through different cell sources and
      biochemical stimuli.
AB  - In this study a scaffoldless approach was employed with two different cell
      sources and biochemical stimuli to engineer a spectrum of fibrocartilages
      representative of the different regions of the knee meniscus. Constructs composed
      of 100% fibrochondrocytes (FC) or a 50:50 co-culture of fibrochondrocytes and
      chondrocytes (CC) were cultured in 10% fetal bovine serum medium or serum-free
      "chondrogenic" medium, each +/-10 ng/mL TGF-beta1 (+T). Constructs from these two
      cell groups and four culture conditions were cultured for 6 weeks. By varying the
      cell type and presence of the growth factor, GAG per dry weight of the constructs
      spanned that of native tissue, ranging 16-45% and 1-7% in the CC and FC groups,
      respectively. Collagen density was most dependent on cell type and was
      significantly lower than tissue values. The collagen I/II ratio could be
      manipulated by cell type and serum presence to span the native range, from 3.5 in
      the serum-free CC group to over 1,000 in the FC groups treated with serum
      containing medium. Using the CC cell group in the presence of serum-free medium
      dramatically increased the compressive stiffness to 128 +/- 34 kPa, similar to
      native tissue. Similarly, serum-free medium or TGF-beta1 treatment enhanced the
      tensile modulus by an order of magnitude, up to 3,000 kPa. Using two cell sources
      and manipulating biochemical stimuli, a range of fibrocartilaginous neotissues
      was engineered. Fibrocartilages such as the knee meniscus are characterized by
      heterogeneity in matrix and functional properties, and this work demonstrates a
      strategy for recreating these heterogeneous tissues.

PMID- 18078297
TI  - Kinetic and stoichiometric parameters estimation in a nitrifying bubble column
      through "in-situ" pulse respirometry.
AB  - This article proposes a simple "in-situ" pulse respirometric method for the
      estimation of four important kinetic and stoichiometric parameters. The method is
      validated in a suspended biomass nitrifying reactor for the determination of (i)
      maximum oxygen uptake rate (OUR(ex)max), (ii) oxidation yield (f(E)), (iii)
      biomass growth yield (f(S)), and (iv) affinity constant (K(S)). OUR(ex)max and
      f(E) were directly obtained from respirograms. In the presented case study, a
      minimum substrate pulse of 10 mgNH(4) (+)-N L(-1) was necessary to determine
      OUR(ex)max which was 61.15 +/- 4.09 mgO(2) L(-1) h(-1) (5 repetitions). A linear
      correlation (r(2) = 0.93) obtained between OUR(ex)max and the biomass
      concentration in the reactor suggests that biomass concentration can be estimated
      from respirometric experiments. The substrate oxidation yield, f(E), was
      determined along 60 days of continuous operation with an average error of 5.6%.
      The biomass growth yield was indirectly estimated from the substrate oxidation
      yield f(E). The average obtained value (0.10 +/- 0.04 mgCOD mg(-1)COD) was in
      accordance with the f(S) estimation by the traditional COD mass balance method
      under steady-state conditions (0.09 +/- 0.01). The affinity constant K(S) was
      indirectly estimated after fitting the ascending part of the respirogram to a
      theoretical model. An average value of 0.48 +/- 0.08 mgNH(4) (+)-N L(-1) was
      obtained, which is in the range of affinity constants reported in the literature
      for the nitrification process (0.16-2 mgNH(4) (+)-N L(-1)).

PMID- 18078298
TI  - Conformational flexibility of a model protein upon immobilization on self
      assembled monolayers.
AB  - The present study reports on the retention of conformational flexibility of a
      model allosteric protein upon immobilization on self-assembled monolayers (SAMs)
      on gold. Organothiolated SAMs of different compositions were utilized for
      adsorptive and covalent attachment of bovine liver glutamate dehydrogenase (GDH),
      a well-characterized allosteric enzyme. Sensitive fluorimetric assays were
      developed to determine immobilization capacity, specific activity, and allosteric
      properties of the immobilized preparations as well as the potential for repeated
      use and continuous catalytic transformations. The allosteric response of the free
      and immobilized forms towards ADP, L-leucine and high concentrations of NAD(+),
      some of the well-known activators for this enzyme, were determined and compared.
      The enzyme immobilized by adsorption or chemical binding responded similarly to
      the activators with a greater degree of activation, as compared to the free form.
      Also loss of activity involving the two immobilization procedures were similar,
      suggesting that residues essential for catalytic activity or allosteric
      properties of GDH remained unchanged in the course of chemical modification. A
      recently established method was used to predict GDH orientation upon
      immobilization, which was found to explain some of the experimental results
      presented. The general significance of these observations in connection with
      retention of native properties of protein structures upon immobilization on SAMs
      is discussed.

PMID- 18078299
TI  - Microfluidic delivery of small molecules into mammalian cells based on
      hydrodynamic focusing.
AB  - Microfluidics-based cell assays offer high levels of automation and integration,
      and allow multiple assays to be run in parallel, based on reduced sample volumes.
      These characteristics make them attractive for studies associated with drug
      discovery. Controlled delivery of drug molecules or other exogenous materials
      into cells is a critical issue that needs to be addressed before microfluidics
      can serve as a viable platform for drug screening and studies. In this study, we
      report the application of hydrodynamic focusing for controlled delivery of small
      molecules into cells immobilized on the substrate of a microfluidic device. We
      delivered calcein AM which was permeant to the cell membrane into cells, and
      monitored its enzymatic conversion into fluorescent calcein during and after the
      delivery. Different ratios of the sample flow to the side flow were tested to
      determine how the conditions of hydrodynamic focusing affected the delivery. A 3D
      numerical model was developed to help understand the fluid flow, molecular
      diffusion due to hydrodynamic focusing in the microfluidic channel. The results
      from the simulation indicated that the calcein AM concentration on the outer
      surface of a cell was determined by the conditions of hydrodynamic focusing. By
      comparing the results from the simulation with those from the experiment, we
      found that the calcein AM concentration on the cell outer surface correlated very
      well with the amount of the molecules delivered into the cell. This suggests that
      hydrodynamic focusing provides an effective way for potentially quantitative
      delivery of exogenous molecules into cells at the single cell or subcellular
      level. We expect that our technique will pave the way to high-throughput drug
      screening and delivery on a microfluidic platform.

PMID- 18078300
TI  - Plasmid DNA transfection using magnetite cationic liposomes for construction of
      multilayered gene-engineered cell sheet.
AB  - Modification of cellular functions by overexpression of genes is being
      increasingly practiced for tissue engineering. In the present study, we
      investigated whether transfection efficiency could be enhanced by magnetofection
      that involves the use of plasmid DNA (pDNA)/magnetite cationic liposomes (MCLs)
      complexes (pDNA/MCL) and magnetic force. The transfection efficiencies of the
      magnetofection technique by pDNA/MCL in fibroblasts and keratinocytes using
      reporter genes were 36- and 10-fold higher, respectively, than those of a
      lipofection technique by cationic liposomes. Moreover, in vitro construction of
      three-dimensional (3D) tissues is an important challenge. We recently proposed a
      novel technique termed "magnetic force-based tissue engineering" (Mag-TE) to
      produce 3D tissues. Since the fibroblasts after magnetofection incorporated both
      magnetite nanoparticles and pDNA, we investigated whether multilayered
      heterotypic cell sheets expressing transgene could be fabricated by Mag-TE.
      First, the fibroblasts were seeded onto an ultra-low attachment culture plate.
      When a magnet was placed under the plate, the cells accumulated at the bottom of
      the culture plate. After 24 h of culture, the transgene-expressing cells formed a
      multilayered cell sheet-like structure. These results indicated that MCLs are a
      potent biomanipulation tool for both gene transfer and 3D tissue construction,
      suggesting that these techniques are useful for tissue engineering.

PMID- 18078301
TI  - Tris(2,4,6-trimethoxyphenyl)methyl carbenium ion for charge derivatization of
      amines and amino acids.
AB  - Primary and secondary alkyl amines substitute readily one of the para-methoxy
      substituents of tris(2,4,6-trimethoxyphenyl)methyl carbenium ion. With this rapid
      process, the preparation of permanently charged positive derivatives of amines,
      amino acids and small C-protected peptides is achieved. This is utilized here to
      facilitate the matrix assisted laser desorption ionization-time-of-flight (MALDI
      TOF) analysis of these compounds.

PMID- 18078302
TI  - A risk calculator for glyphosate resistance in Lolium rigidum (Gaud.).
AB  - BACKGROUND: Glyphosate resistance has been confirmed in 58 populations of Lolium
      rigidum (Gaud.), a major weed of crops in southern Australia. Extensive use of
      glyphosate in conjunction with minimal soil disturbance has been identified as
      high risk for resistance to that herbicide. Land managers need a simple method
      for rapid assessment of the risk of resistance occurring as a result of past and
      proposed future management practices. Modelled on risk assessment nomographs, a
      simple calculator for indicating the risk of evolved glyphosate resistance in L.
      rigidum is described. RESULTS: The calculator uses the generations since first
      use and the frequency of use of glyphosate in combination with historical
      cultivation levels as critical factors for determining the risk of glyphosate
      resistance evolution. Based on the management history of a field, a land manager
      can graphically determine a glyphosate resistance risk for that field.
      CONCLUSION: The calculator enables the farmer or the advisor to assess the risk
      of a weed's population becoming resistant and modify practices accordingly to
      manage for sustainable glyphosate use. The risk calculator could be modified for
      other herbicides and different weed species.

PMID- 18078303
TI  - Discovery and synthesis of a new bis(thiourea)-Pd pincer guided by ESI-MS/MS.

PMID- 18078304
TI  - Glyphosate-resistant crops: adoption, use and future considerations.
AB  - BACKGROUND: Glyphosate-resistant crops (GRCs) were first introduced in the United
      States in soybeans in 1996. Adoption has been very rapid in soybeans and cotton
      since introduction and has grown significantly in maize in recent years. GRCs
      have grown to over 74 million hectares in five crop species in 13 countries. The
      intent of this paper is to update the hectares planted and the use patterns of
      GRC globally, and to discuss briefly future applications and uses of the
      technology. RESULTS: The largest land areas of GRCs are occupied by soybean (54.2
      million ha), maize (13.2 million ha), cotton (5.1 million ha), canola (2.3
      million ha) and alfalfa (0.1 million ha). Currently, the USA, Argentina, Brazil
      and Canada have the largest plantings of GRCs. Herbicide use patterns would
      indicate that over 50% of glyphosate-resistant (GR) maize hectares and 70% of GR
      cotton hectares receive alternative mode-of-action treatments, while
      approximately 25% of GR soybeans receive such a treatment in the USA. Alternative
      herbicide use is likely driven by both agronomic need and herbicide resistance
      limitations in certain GR crops such as current GR cotton. Tillage practices in
      the USA indicate that > 65% of GR maize hectares, 70% of GR cotton hectares and
      50% of GR soybean hectares received some tillage in the production system.
      Tillage was likely used for multiple purposes ranging from seed-bed preparation
      to weed management. CONCLUSION: GRCs represent one of the more rapidly adopted
      weed management technologies in recent history. Current use patterns would
      indicate that GRCs will likely continue to be a popular weed management choice
      that may also include the use of other herbicides to complement glyphosate.
      Stacking with other biotechnology traits will also give farmers the benefits and
      convenience of multiple pest control and quality trait technologies within a
      single seed.

PMID- 18078305
TI  - Comparison of herbicide regimes and the associated potential environmental
      effects of glyphosate-resistant crops versus what they replace in Europe.
AB  - While cultivation of transgenic crops takes place in seven of the EU member
      states, this constitutes a relatively limited part of the total acreage planted
      to these crops worldwide. The only glyphosate-resistant (GR) crop grown
      commercially until recently has been soybean in Romania. In addition, large-scale
      experimental European data exist for GR sugar and fodder beets, and, to a lesser
      extent, GR oilseed rape. These GR crops are likely to have an impact both on the
      use of herbicides and on the environmental impact of the latter. From the data on
      these GR crops, it appears that quantities of herbicides applied to GR beets are
      decreased while those on GR soybean are slightly increased compared with their
      conventional counterparts. Depending on the parameters used for prediction or
      measurement of environmental impacts of GR crops, generally similar or less
      negative impacts were observed compared with conventional crops. Favourable
      environmental effects of the glyphosate-containing herbicide regimes on GR crops
      appear feasible, provided appropriate measures for maintaining biodiversity and
      prevention of volunteers and gene flow are applied.

PMID- 18078306
TI  - A new MRI method, tested in vitro for the assessment of thermal coagulation and
      demonstrated in vivo on focused ultrasound ablation.
AB  - A new MRI method is described. It is implemented for the assessment of thermal
      coagulation after thermal treatment. The method does not require injection of a
      contrast agent. The image is based on the amount of magnetization exchange
      between macromolecules and water in the tissue. Coagulated tissue has a faster
      magnetization exchange rate, forming the new contrast. In this study, the new
      imaging method is shown to have good contrast between coagulated and untreated
      excised tissues of porcine liver and muscle. The method is also successfully
      demonstrated in vivo in rat thigh muscle thermally treated with focused
      ultrasound.

PMID- 18078307
TI  - Using forward calculations of the magnetic field perturbation due to a realistic
      vascular model to explore the BOLD effect.
AB  - This paper assesses the reliability of the infinite cylinder model used
      previously in the literature to simulate blood oxygenation level dependent (BOLD)
      signal changes. A three-dimensional finite element method was applied to a
      realistic model of the cortical vasculature, and the results compared with those
      generated from a simple model of the vasculature as a set of independent,
      randomly oriented, infinite cylinders. The realistic model is based on scanning
      electron microscopy measurements of the terminal vascular bed in the superficial
      cortex of the rat. Good agreement is found between the two models with regard to
      the extravascular R(2)* and R(2) dependence on the cerebral blood volume and
      blood oxygenation fraction. Using the realistic model, it is also possible to
      gain further understanding of the relative importance of intravascular and
      extravascular BOLD contrast. A simple parameterisation of the dependence of the
      relaxation rates on relative cerebral blood volume and blood-tissue
      susceptibility difference was carried out, allowing discussion of the variation
      in the form of the haemodynamic response with field strength.

PMID- 18078308
TI  - Preparation, characterization, and application of biotinylated and biotin
      PEGylated glucagon-like peptide-1 analogues for enhanced oral delivery.
AB  - Glucagon-like peptide-1 (GLP-1) (7-36) is a type of incretin hormone with unique
      antidiabetic potential. The introduction of orally active GLP-1 offers
      substantial benefits in the treatment of type 2 diabetes over conventional
      injection-based therapies. Because the intestinal absorption of GLP-1 is
      restricted by its natural characteristics, we developed a series of GLP-1
      analogues via the site-specific conjugation of biotin-NHS and/or of biotin
      poly(ethylene glycol)-NHS at Lys 26 and Lys 34 of GLP-1 (7-36), respectively, in
      order to improve oral delivery. The resultant GLP-1 analogues, Lys 26,34-DiBiotin
      GLP-1 (DB-GLP-1) and Lys 26-Biotin-Lys 34-(Biotin-PEG)-GLP-1 (DBP-GLP-1), were
      prepared and studied in terms of their chemical, structural, and biological
      properties. DBP-GLP-1 demonstrated superior proteolytic stability against
      trypsin, intestinal fluid, and the major GLP-1 inactivation enzyme (dipeptidyl
      peptidase-IV (DPP-IV)) to native GLP-1 or DB-GLP-1 ( p < 0.001). The in vitro
      insulinotropic effects of DB-GLP-1 and DBP-GLP-1 showed potent biological
      activity in a dose-dependent manner, which resembled that of native GLP-1 in
      terms of stimulating insulin secretion in isolated rat islets of Langerhans.
      Intraperitoneal glucose tolerance tests (IPGTT) after the oral administration of
      GLP-1 analogues in diabetic db/db mice demonstrated that DB-GLP-1 and DBP-GLP-1
      significantly reduced the AUC 0-180 min of glucose for 3 h by 14.9% and 24.5%
      compared to that of native GLP-1, respectively ( p < 0.01). In particular, DBP
      GLP-1 concentration in plasma rapidly increased 30 min after oral administration
      in rats, presumably due to improved intestinal absorption. These findings
      revealed that site-specific biotinylated and biotin-PEGylated GLP-1 is absorbed
      by intestine and that it has biological activity in vivo. Therefore, we propose
      that this orally active bioconjugated GLP-1 might be considered as a potential
      oral antidiabetic agent for type 2 diabetes mellitus.

PMID- 18078310
TI  - Statistical validation of peptide identifications in large-scale proteomics using
      the target-decoy database search strategy and flexible mixture modeling.
AB  - Reliable statistical validation of peptide and protein identifications is a top
      priority in large-scale mass spectrometry based proteomics. PeptideProphet is one
      of the computational tools commonly used for assessing the statistical confidence
      in peptide assignments to tandem mass spectra obtained using database search
      programs such as SEQUEST, MASCOT, or X! TANDEM. We present two flexible methods,
      the variable component mixture model and the semiparametric mixture model, that
      remove the restrictive parametric assumptions in the mixture modeling approach of
      PeptideProphet. Using a control protein mixture data set generated on an linear
      ion trap Fourier transform (LTQ-FT) mass spectrometer, we demonstrate that both
      methods improve parametric models in terms of the accuracy of probability
      estimates and the power to detect correct identifications controlling the false
      discovery rate to the same degree. The statistical approaches presented here
      require that the data set contain a sufficient number of decoy (known to be
      incorrect) peptide identifications, which can be obtained using the target-decoy
      database search strategy.

PMID- 18078309
TI  - Matrix metalloproteinase-assisted triggered release of liposomal contents.
AB  - We offer a novel methodology for formulating liposomes by incorporating sequence
      specific collagen-mimetic peptides such that they are specifically "uncorked" by
      a matrix metalloproteinase, MMP-9. By encapsulating carboxyfluorescein (as a self
      quenching fluorescent dye), we demonstrate that the time-dependent release of the
      dye from liposomes is due to the specific enzymatic cleavage of the surface
      exposed collagen-mimetic peptides. The specificity of such cleavage is attested
      by the fact that the liposomal "uncorking" and their content release occur only
      by MMP-9 and not by a general proteolytic enzyme, trypsin, despite the fact that
      the collagen mimetic peptides contain the trypsin cleavage site. The mechanistic
      details underlying the formulations of liposomes and their enzyme-selective
      "uncorking" and content release are discussed. Arguments are presented that such
      liposomes can be fine-tuned to serve as the drug delivery vehicles for the
      detection and treatment of various human diseases, which occur due to the
      overexpression of a variety of pathogenic matrix metalloproteinases.

PMID- 18078311
TI  - Synthesis and evaluation of N-methyl and S-methyl 11C-labeled 6-methylthio-2-(4'
      N,N-dimethylamino)phenylimidazo[1,2-a]pyridines as radioligands for imaging beta
      amyloid plaques in Alzheimer's disease.
AB  - 6-Thiolato-substituted 2-(4'- N,N-dimethylamino)phenylimidazo[1,2- a]pyridines (
      RS-IMPYs; 1- 4) were synthesized as candidates for labeling with carbon-11 ( t
      1/2 = 20.4 min) and imaging of A beta plaques in living human brain using
      positron emission tomography (PET). K i values for binding of these ligands to
      Alzheimer's disease brain homogenates were measured in vitro against tritium
      labeled 6 (Pittsburgh compound B). MeS-IMPY ( 3, K i = 7.93 nM) was labeled with
      carbon-11 at its S- or N-methyl position to give [ (11)C] 7 or [ (11)C] 8,
      respectively. After injection into rats, [ (11)C] 7 or [ (11)C] 8 gave moderately
      high brain uptakes of radioactivity followed by rapid washout to low levels. The
      ratio of radioactivity at maximal uptake to that at 60 min reached 18.7 for [
      (11)C] 7. [ (11)C] 7 behaved similarly in mouse and monkey. [ (11)C] 7 also bound
      selectively to A beta plaques in post mortem human Alzheimer's disease brain.
      Although rapidly metabolized in rat by N-demethylation, [ (11)C] 7 was stable in
      rat brain homogenates. The ex vivo brain radiometabolites observed in rats have a
      peripheral origin. Overall, [ (11)C] 7 merits further evaluation in human
      subjects.

PMID- 18078312
TI  - A Novel iron-chelating derivative of the neuroprotective peptide NAPVSIPQ shows
      superior antioxidant and antineurodegenerative capabilities.
AB  - Affecting an estimated 5% of adults over 65 years of age, Parkinson's disease and
      Alzheimer's disease are the most common neurodegenerative disorders. Accumulating
      evidence suggests that oxidative stress induced by the breakdown of iron
      homeostasis is a major contributor to the neuronal loss observed in
      neurodegeneration. Thus, brain-permeable iron chelators may present potential
      therapeutic benefits. In the present study, iron-chelating hydroxamate groups
      were introduced into the NAP (NAPVSIPQ) peptide, whose neuroprotective qualities
      have been widely demonstrated. Our experiments revealed that the novel
      dihydroxamate peptide 3 is capable of inhibiting iron-catalyzed hydroxyl radical
      formation and lipid peroxidation, abilities that are not part of the repertoire
      of its parent peptide. In addition, peptide 3 was superior to native NAP in
      protecting human neuroblastoma cell cultures against the toxicity of hydrogen
      peroxide. These results suggest that NAP-based iron chelators deserve further
      investigation in the search for drug candidates for neurodegeneration.

PMID- 18078313
TI  - Structural modification of an angiogenesis inhibitor discovered from traditional
      Chinese medicine and a structure-activity relationship study.
AB  - Pseudolaric acid B (PAB), discovered as a promising angiogensis inhibitor, was
      served as the anticancer drug lead, and a series of its derivatives were
      synthesized. Among them, some derivatives, such as 13c- 13k, exhibited potent
      inhibition on the HMEC-1 cell proliferation and strong cytotoxic activities
      against the tested six tumor cell lines. The PAB derivatives 13c- 13k also showed
      significant and specific inhibition on HMEC-1 cell migration in vitro, and only
      13d expressed moderate activity against HMEC-1 cell tube formation. The in vitro
      anticancer tests of the selected natural PAB analogs and the structurally
      modified PAB derivatives have led to the establishment of a clear structure
      activity relationship.

PMID- 18078314
TI  - Quantitative high-throughput analysis of 16 (fluoro)quinolones in honey using
      automated extraction by turbulent flow chromatography coupled to liquid
      chromatography-tandem mass spectrometry.
AB  - A method making use of turbulent flow chromatography automated online extraction
      with tandem mass spectrometry (MS/MS) was developed for the analysis of 4
      quinolones and 12 fluoroquinolones in honey. The manual sample preparation was
      limited to a simple dilution of the honey test portion in water followed by a
      filtration. The extract was online purified on a large particle size extraction
      column where the sample matrix was washed away while the analytes were retained.
      Subsequently, the analytes were eluted from the extraction column onto an
      analytical column by means of an organic solvent prior to chromatographic
      separation and MS detection. Validation was performed at three fortification
      levels (i.e., 5, 20, and 50 microg/kg) in three different honeys (acacia,
      multiflower, and forest) using the single-point calibration procedure by means of
      either a 10 or 25 microg/kg calibrant. Good recovery (85-127%, median 101%) as
      well as within-day (2-18%, median 6%) and between-day (2-42%, median 9%)
      precision values was obtained whatever the level of fortification and the analyte
      surveyed. Due to the complexity of the honey matrix and the large variation of
      the MS/MS transition reaction signals, which were honey-dependent, the limit of
      quantification for all compounds was arbitrarily set at the lowest fortification
      level considered during the validation, e.g., 5 microg/kg. This method has been
      successfully applied in a minisurvey of 34 honeys, showing ciprofloxacin and
      norfloxacin as the main (fluoro)quinolone antibiotics administered to treat
      bacterial diseases of bees. Turbulent flow chromatography coupled to LC-MS/MS
      showed a strong potential as an alternative method compared to those making use
      of offline sample preparation, in terms of both increasing the analysis
      throughput and obtaining higher reproducibility linked to automation to ensure
      the absence of contaminants in honey samples.

PMID- 18078315
TI  - Impact of fermentation on phenolic compounds in leaves of pak choi (Brassica
      campestris L. ssp. chinensis var. communis) and Chinese leaf mustard (Brassica
      juncea coss).
AB  - Four different cultivars of Chinese Brassica vegetables (two pak choi cultivars
      and two Chinese leaf mustard cultivars) were fermented according to a traditional
      Chinese method called pickling. The plant material was investigated before and
      after the fermentation procedure to determine the qualitative and quantitative
      changes in its polyphenols. A detailed description of the identified phenolic
      compounds of leaf mustard by HPLC-ESI-MS(n) is presented here for the first time,
      including hydroxycinnamic acid mono- and diglycosides (gentiobioses) and
      flavonoid tetraglycosides. Flavonoid derivatives with a lower molecular mass (di-
      and triglycosides) and aglycones of flavonoids and hydroxycinnamic acids were
      detected in fermented cabbages compared to the main compounds detected in
      nonfermented cabbages (tri- and tetraglycosides of flavonoids and hydroxycinnamic
      acid derivatives of malic acid, glycoside, and quinic acid). During the
      fermentation process, contents of flavonoid derivatives and some hydroxycinnamic
      acid derivatives were found to decrease. Some marginal losses of polyphenols were
      observed even in the kneading step of the plant material prior to the
      fermentation procedure. The antioxidative potential of fermented cabbages was
      much higher compared to that of nonfermented cabbages in the TEAC assay, but not
      observable in the DPPH assay. The increase of the antioxidative potential
      detected in the TEAC assay was attributed to the qualitative changes of
      polyphenols as well as other reductones potentially present.

PMID- 18078316
TI  - Effect of apple cell walls and their extracts on the activity of dietary
      antioxidants.
AB  - The effect of dietary fiber in the form of apple cell walls and pectin extracts
      on natural antioxidants was examined. Cell walls (CW), isolated from apples (
      Malus domestica Borkh. cv. "Pacific Rose"), were incubated with ascorbic acid
      (AA) or quercetin in N-2-hydroxyethylpiperazine- N'-2-ethanesulfonic acid (HEPES)
      buffer (pH 6.5) at 37 degrees C for 2 h. The resulting supernatants were
      characterized by a ferric reducing antioxidant power (FRAP) assay and cyclic
      voltammetry (CV). The experiments were repeated with pectin isolated from the
      apple cell walls and commercial pectins and showed that polysaccharide
      preparations stabilized AA effectively but offered little protection against
      quercetin oxidation. The water-soluble components from cell walls appeared to be
      responsible for the observed effects of cell-wall polysaccharide preparations on
      antioxidant activity.

PMID- 18078317
TI  - Characterization of the most odor-active volatiles of orange wine made from a
      Turkish cv. Kozan (Citrus sinensis L. Osbeck).
AB  - The aroma-active compounds of cv. Turkish Kozan orange wine were analyzed by
      sensory and instrumental analyses. Liquid-liquid extraction with dichloromethane
      was used for extraction of volatile components. According to sensory analysis,
      the aromatic extract obtained by liquid-liquid extraction was representative of
      orange wine odor. A total of 63 compounds were identified and quantified in
      orange wine. The results of the gas chromatography-olfactometry analysis showed
      that 35 odorous compounds were detected by the panelists. Of these, 28 aroma
      active compounds were identified. Alcohols followed by terpenes and esters were
      the most abundant aroma-active compounds of the orange wine. Among these
      compounds, ethyl butanoate (fruity sweet), 3-methyl-1-pentanol (roasty), linalool
      (floral citrusy), gamma-butyrolactone (cheesy burnt sugar), 3-(methylthio)
      propanol (boiled potato, rubber), geraniol (floral citrusy), and 2-phenylethanol
      (floral rose) were the most important contributors to the aroma of the orange
      wine because they were perceived by all eight panelists.

PMID- 18078318
TI  - Determination of the bulk moisture diffusion coefficient for corn starch using an
      automated water sorption instrument.
AB  - The bulk moisture diffusion coefficient (Db) is an important physical parameter
      of food ingredients and systems. However, the traditional method of measuring Db
      using saturated salt solutions is very time-consuming and cumbersome. New
      automated water sorption instruments, which can be used to conveniently and
      precisely control both relative humidity and temperature, provide a faster, more
      robust method for collecting the data needed for determining Db. Thus, the
      objectives of this study were to (1) investigate the use of the DVS instrument
      for collecting the data needed for determining the adsorption (Dba) and
      desorption (Dbd) bulk moisture diffusion coefficients for dent corn starch as a
      function of relative humidity and (2) determine the effect of temperature on Dba
      for dent corn starch at a constant relative humidity. Kinetic water sorption
      profiles of dent corn starch were obtained at eight relative humidity values
      ranging from 10 to 80% at 10% intervals at 25 degrees C and at five temperatures,
      15, 20, 25, 30, and 35 degrees C, at 50% relative humidity using a DVS
      instrument. Db was calculated from the kinetic water sorption profiles using the
      full solution of Fick's second law for the thin slab model, as well as the slope
      method, a simplification of the full model. The Dba of dent corn starch at 25
      degrees C reached a maximum at intermediate relative humidity values, after which
      Dba decreased due to a change in the moisture diffusion mechanism from vapor to
      liquid diffusion. The Dbd of dent corn starch at 25 degrees C remained nearly
      constant as a function of relative humidity. The Dba for dent corn starch
      increased as temperature increased from 15 to 35 degrees C, with an activation
      energy of 38.85 +/- 0.433 kJ/mol.

PMID- 18078319
TI  - Characterization of volatiles in unhopped wort.
AB  - The volatile fraction of wort components was studied during boiling. Not less
      than 118 volatile compounds were identified when unhopped pilsner wort was boiled
      and samples of wort and condensed vapors were analyzed with headspace SPME-GC/MS,
      of which 54 were confirmed with reference compounds. The wort samples contained
      61 identifiable compounds, while the vapor condensate yielded 108 different
      compounds. Almost 30 known compounds were found that have not been described
      before in unhopped pilsner wort. One previously unknown aldol reaction product
      was tentatively identified as 2-phenyl-2-octenal. The detection of branched 2
      alkenals underlines the importance of the aldol condensation in Maillard-type
      reactions, while the tentative identification of alkyloxazoles and alkylthiazoles
      could once more accentuate the central role of alpha-dicarbonyl compounds,
      aldehydes, and amino acids in flavor generation. The condensation of wort vapors
      joined with the SPME-GC/MS technique has proven to be a useful tool in volatile
      analysis.

PMID- 18078320
TI  - Reversibility of structural changes of polypeptides in multilayer nanofilms.
AB  - Structural properties of different polypeptide multilayer nanofilms fabricated at
      neutral pH have been analyzed by UV spectroscopy, circular dichroism spectroscopy
      (CD), and Fourier-transform infrared spectroscopy (FTIR). The various peptides
      studied exhibit a strong tendency to adopt a beta sheet conformation in the
      films. Changes in film structure on dehydration are completely reversed on
      rewetting. The time scale of reversibility is, however, substantially shorter for
      the polymer backbone than the side chains, as in protein folding.

PMID- 18078321
TI  - An in situ study of collagen self-assembly processes.
AB  - We present in situ studies on the self-assembly and dynamic evolution of collagen
      gels from semidilute solutions in a microfluidic device. Collagen fibrils not
      only reinforce the mechanical properties of bone and tissues, but they also
      influence cellular motility and morphology. We access the initial steps of the
      hierarchical self-assembly of collagen fibrils and networks by using hydrodynamic
      focusing to form oriented fibers. The accurate description of the conditions
      within the microchannel requires a numerical expression for the pH in the device
      as well as a modified mathematical description of the viscosity, which increases
      nearly 300-fold as collagen fibrils form around neutral pH. Finite element
      modeling profiles overlay impressively with cross-polarized microscopy images of
      the birefringent fibrils in the channel. Real-time X-ray microdiffraction
      measurements in flow indicate an enhanced supramolecular packing having a unit
      spacing commensurate with that of a pentameric collagen subunit. These results
      have significant implications for the field of biomedicine, wherein new aligned,
      cellularly active, and mechanically strengthened materials continue to be in
      demand. However, this work is also remarkable from a more fundamental,
      biophysical point of view because the underlying concepts may be generalized to a
      large pool of systems.

PMID- 18078322
TI  - Stable stealth function for hollow polyelectrolyte microcapsules through a
      poly(ethylene glycol) grafted polyelectrolyte adlayer.
AB  - Prospective biomedical applications of hollow polyelectrolyte microcapsules, for
      example, as drug delivery systems, require surface modifications that help to
      escape clearance by the mononuclear phagocytic system (MPS). Layer-by-layer
      assembled microcapsules that were alternatingly composed of polystyrene sulfonate
      (PSS) and polyallylamine hydrochloride (PAH) were coated with adlayers of
      poly(ethylene glycol) (PEG)-grafted poly-L-lysine (PLL-g-PEG) and poly-L-glutamic
      acid (PGA-g-PEG). Their effects on MPS recognition were studied in primary cell
      cultures of human monocyte derived dendritic cells and macrophages. PGA-g-PEG
      coatings had no significant effect on cellular recognition, which may be
      explained by insufficient PEG density of the adlayer. Contrary, PLL-g-PEG
      effectively blocked phagocytosis of coated microcapsules. In addition, PLL-g-PEG
      coatings showed efficient adlayer stability for at least 3 weeks, and PAH/PSS
      microcapsules did not impair phagocyte viability. Our results demonstrate that
      layer-by-layer assembled polyelectrolyte microcapsules coated with a PEG-grafted
      polyelectrolyte, PLL-g-PEG, represent a promising platform for a drug delivery
      system that escapes fast clearance by the MPS.

PMID- 18078323
TI  - Chitosan nanofibers from an easily electrospinnable UHMWPEO-doped chitosan
      solution system.
AB  - Conversion of natural biopolymer chitosan into nanofibers through electrospinning
      has significant usefulness in various biomedical applications, in particular, for
      constructing a biomimetic and bioactive nanofibrous artificial extracellular
      matrix for engineering various tissues. Here, we show that introduction of an
      ultrahigh-molecular-weight poly(ethylene oxide) (UHMWPEO) into aqueous chitosan
      solutions remarkably enhances the formation of chitosan nanofibrous structure and
      leads to much lower loading of the water soluble fiber-forming aiding agent of
      PEO down to 5 wt % as compared to previous high PEO loadings in the electrospun
      chitosan nanofibers. The excellent electrospinnability of the current formulation
      renders electrospinning of natural biopolymer chitosan a robust process for large
      scale production of practically applicable nanofibrous structures.

PMID- 18078324
TI  - Structural disorder in silk proteins reveals the emergence of elastomericity.
AB  - Spider silks combine basic amino acids into strong and versatile fibers where the
      quality of the elastomer is attributed to the interaction of highly adapted
      protein motifs with a complex spinning process. The evaluation, however, of the
      interaction has remained elusive. Here, we present a novel analysis to study silk
      formation by examining the secondary structures of silk proteins in solution.
      Using the seven different silks of Nephila edulis as a benchmark system, we
      define a structural disorder parameter (the folding index, gamma). We found that
      gamma is highly correlated with the ratio of glycine present. Testing the
      correlation between glycine content and the folding index (gamma) against a
      selected range of silks, we find quantitatively that, in order to achieve
      specialization with changes in mechanical performance, the spider's silks require
      higher structural flexibility at the expense of reduced stability and
      consequently an increased conversion-energy cost. Taken together, our biophysical
      and evolutionary findings reveal that silk elastomericity evolved in tandem with
      specializations in the process of silk spinning.

PMID- 18078325
TI  - Structure-property studies on carbohydrate-derived polymers for use as protein
      resistant biomaterials.
AB  - Here we describe structure-property studies on our carbohydrate-derived side
      chain ether polymers as protein-resistant biomaterials. A series of side-chain
      ether polymers, including two polyesters and two polyamides, were prepared by
      condensation polymerization of monomers derived from simple carbohydrates. The
      two side-chain permethoxylated polyesters having different stereochemical
      repeating units demonstrate excellent resistance toward nonspecific protein
      adsorption as shown by surface plasmon resonance, indicating that the polymer
      stereochemistry does not have much effect on its protein-resistant properties.
      The introduction of amide bonds to polymer backbones leads to more pronounced
      effects. While the polymer degradation stability is significantly enhanced by
      replacing ester with amide linkages, the protein resistance for the polymer is
      greatly reduced by introduction of amide bonds. Finally, our results suggest that
      free hydroxyl and amide groups, while both are hydrogen-bond donors, seem to have
      different effects on protein resistant properties for polymers. It appears that
      free amide groups have more detrimental effect on protein resistance than free
      hydroxyl groups. These results show that the protein-resistant properties of this
      family of polymers can be tailored by modifying the backbone and side chain
      functionalities. In combination with the biodegradability and
      functionalizability, this family of carbohydrate-derived polymers shows promise
      as versatile biomaterials for biomedical applications.

PMID- 18078326
TI  - Limonoids and sesquiterpenoids from Amoora tsangii.
AB  - Seven new limonoids, amotsangins A-G (1-7), two known limonoids, and four known
      sesquiterpenoids were isolated from the twigs and leaves of Amoora tsangii. Their
      structures were elucidated primarily on the basis of spectroscopic data.

PMID- 18078327
TI  - Biologically active aspidofractinine alkaloids from Kopsia singapurensis.
AB  - Ten new indole alkaloids of the aspidofractinine type, in addition to several
      recently reported indole alkaloids and 20 other known alkaloids, were obtained
      from the leaf and stem-bark extract of the Malayan Kopsia singapurensis, viz.,
      kopsimalines A-E (1-5), kopsinicine (6), kopsofinone (7), and kopsiloscines H-J
      (8-10). The structures of these alkaloids were determined using NMR and MS
      analysis. Kopsimalines A (1), B (2), C (3), D (4), and E (5) and kopsiloscine J
      (10) were found to reverse multidrug-resistance in vincristine-resistant KB
      cells, with 1 showing the highest potency.

PMID- 18078328
TI  - Solamargine enhances HER2 expression and increases the susceptibility of human
      lung cancer H661 and H69 cells to trastuzumab and epirubicin.
AB  - We have previously demonstrated that solamargine (SM), the major steroidal
      glycoalkaloid extracted from Chinese herb Solanum plants, reveals down-regulation
      of HER2 and up-regulation of Fas and tumor necrosis factor receptor (TNFR)
      expressions, triggers the mitochondria-mediated cell apoptosis pathway, and
      sensitizes human nonsmall cell lung cancer (NSCLC) H441 and A549 adenocarcinoma
      cells to chemotherapy. The present study shows that SM enhances HER2 expression
      in NSCLC large cell carcinoma H661 and small cell lung cancer (SCLC) H69 cells
      and may increase the susceptibility of the cells to trastuzumab, the humanized
      anti-HER2 antibody. The combinational treatment of SM and trastuzumab
      synergistically augments and inhibits H661 and H69 cell proliferation. After
      treatment with SM, coexpression of HER2 and topoisomerase IIalpha (TOP2A) H661
      and H69 cells is more sensitive to the TOP2 inhibitor, epirubicin. The
      combinatory use of low concentrations of SM with the low-toxic epirubicin
      accelerated greater apoptotic cell death than each drug did alone in H661 and H69
      cells. Relevant studies have shown that HER2 overexpressing cancer cells are more
      resistant than HER2 low-expressing cells to the chemotherapeutic agent and tumor
      necrosis factor-induced apoptosis. These investigations have indicated that HER2
      overexpression does not suffice to induce intrinsic and pleomorphic drug
      resistance. The data presented herein suggest that the expression of HER2 did not
      influence the SM-induced apoptosis of different types of lung cancer cells and
      that the SM up-regulation of HER2 and TOP2A expressions simultaneously augmented
      trastuzumab and epirubicin-induced deaths of lung cancer H661 and H69 cells.

PMID- 18078329
TI  - Characterization of a novel alpha1,2-fucosyltransferase of Escherichia coli
      O128:b12 and functional investigation of its common motif.
AB  - The wbsJ gene from Escherichia coli O128:B12 encodes an alpha1,2
      fucosyltransferase responsible for adding a fucose onto the galactose residue of
      the O-antigen repeating unit via an alpha1,2 linkage. The wbsJ gene was
      overexpressed in E. coli BL21 (DE3) as a fusion protein with glutathione S
      transferase (GST) at its N-terminus. GST-WbsJ fusion protein was purified to
      homogeneity via GST affinity chromatography followed by size exclusion
      chromatography. The enzyme showed broad acceptor specificity with
      Galbeta1,3GalNAc (T antigen), Galbeta1,4Man and Galbeta1,4Glc (lactose) being
      better acceptors than Galbeta-O-Me and galactose. Galbeta1,4Fru (lactulose), a
      natural sugar, was furthermore found to be the best acceptor for GST-WbsJ with a
      reaction rate four times faster than that of lactose. Kinetic studies showed that
      GST-WbsJ has a higher affinity for lactose than lactulose with apparent Km values
      of 7.81 mM and 13.26 mM, respectively. However, the kcat/appKm value of lactose
      (6.36 M(-1) x min(-1)) is two times lower than that of lactulose (13.39 M(-1) x
      min(-1)). In addition, the alpha1,2-fucosyltransferase activity of GST-WbsJ was
      found to be independent of divalent metal ions such as Mn2+ or Mg2+. This
      activity was competitively inhibited by GDP with a Ki value of 1.41 mM. Site
      directed mutagenesis and a GDP-bead binding assay were also performed to
      investigate the functions of the highly conserved motif H152xR154R155xD157. In
      contrast to alpha1,6-fucosyltransferases, none of the mutants of WbsJ within this
      motif exhibited a complete loss of enzyme activity. However, residues R154 and
      D157 were found to play critical roles in donor binding and enzyme activity. The
      results suggest that the common motif shared by both alpha1,2-fucosyltransferases
      and alpha1,6-fucosyltransferases have similar functions. Enzymatic synthesis of
      fucosylated sugars in milligram scale was successfully performed using Galbeta-O
      Me and Galbeta1,4Glcbeta-N3 as acceptors.

PMID- 18078330
TI  - Reactivity of sulfenic acid in human serum albumin.
AB  - Sulfenic acid is formed upon oxidation of thiols and is a central intermediate in
      the redox modulation of an increasing number of proteins. Methods for quantifying
      or even detecting sulfenic acid are scarce. Herein, the reagent 7-chloro-4
      nitrobenz-2-oxa-1,3-diazole was determined not to be suitable as a chromophoric
      probe for sulfenic acid in human serum albumin (HSA-SOH) because of lack of
      specificity. Thionitrobenzoate (TNB) reacted with HSA exposed to hydrogen
      peroxide, but not control or thiol-blocked HSA. The reaction was biphasic. The
      first phase was approximately 20-fold faster than the second phase and first
      order in HSA-SOH and TNB (105 +/- 11 M-1 s-1, 25 degrees C, pH 7.4), allowing
      quantitative data on HSA-SOH formation and reactivity to be obtained. Exposure of
      reduced HSA (0.5 mM) to hydrogen peroxide (4 mM, 37 degrees C, 4 min) yielded
      0.18 +/- 0.02 mol of HSA-SOH per mol of HSA. HSA-SH reacted with hydrogen
      peroxide at 2.7 +/- 0.7 M-1 s-1 (37 degrees C, pH 7.4), while HSA-SOH reacted at
      0.4 +/- 0.2 M-1 s-1, yielding sulfinic acid (HSA-SO2H), as detected by mass
      spectrometry. The rate constants of HSA-SOH with targets of analytical interest
      such as dimedone and sodium arsenite were determined. HSA-SOH did not react
      appreciably with the plasma reductants ascorbate or urate, nor with free basic
      amino acids. In contrast, HSA-SOH reacted rapidly with the plasma thiols
      cysteine, glutathione, homocysteine, and cysteinylglycine at 21.6 +/- 0.2, 2.9 +/
      0.5, 9.3 +/- 0.9, and 55 +/- 3 M-1 s-1 (25 degrees C, pH 7.4), respectively,
      supporting a role for HSA-SOH in the formation of mixed disulfides.

PMID- 18078332
TI  - Strongly luminescent palladium(0) and platinum(0) diphosphine complexes.
AB  - The synthesis, structure, and photoluminescence of palladium(0) and platinum(0)
      complexes containing biarydiphosphines, biphep (biphep = 2,2'
      bis(diphenylphosphino)-1,1'-biphenyl) and binap (binap = 2,2'
      bis(diphenylphosphino)-1,1'-binaphthyl) have been studied. X-ray structure
      analysis of [Pt(biphep)(2)] revealed the distorted-tetrahedral geometry of the
      complex. The photophysical properties of the three complexes [Pd(biphep)(2)],
      [Pt(biphep)(2)], and [Pd(binap)(2)] were investigated and compared with that of
      the previously reported [Pt(binap)(2)] complex. The [Pd(biphep)(2)] complex shows
      the strongest luminescence with a high quantum yield (38%) and a long lifetime
      (3.2 micros) in a toluene solution at room temperature. The luminescence should
      be due to metal-to-ligand charge transfer excited states. At room temperature,
      radiative rate constants of the four complexes show similar values. The
      difference in the luminescent properties should reflect the different
      nonradiative rate constants of the complexes. The temperature-dependence of the
      luminescence spectra and lifetime of the complexes were also discussed.

PMID- 18078331
TI  - Two-dimensional infrared spectroscopy as a probe of the solvent electrostatic
      field for a twelve residue peptide.
AB  - The linear IR and two-dimensional (2D) IR spectra of the amide-I modes of the 12
      residue beta-hairpin peptide tryptophan zipper-2 (SWTWENGKWTWK) and its two 13C
      isotopomers were simulated, with local mode frequencies evaluated by two solution
      phase peptide amide-I frequency maps proposed recently: an electrostatic
      potential map and an electrostatic field map. Both maps predict a set of
      nondegenerate local amide-I mode transition energies for the hairpin. Spectral
      simulations using both maps predict the main spectral features of the linear IR
      and 2D IR experimental results of the (13)C-labeled and -unlabeled hairpin. The
      radial distribution functions obtained using trajectories from classical
      molecular dynamics simulations demonstrate different water distributions at
      different sites of the hairpin. Our results suggest that the observed difference
      of the (13)C-shifted band, including its peak position and frequency
      distributions for different isotopomers, in both linear IR and 2D IR spectra, is
      likely to be due to the difference in the local environment of the solvated
      peptide. Ab initio density functional theory calculations show a residue
      independent (13)C shift of the amide-I mode, further supporting the result. The
      variations of these shifts are attributed to the residue level heterogeneity of
      the electrostatic environment of the peptide. Our results show that 2D IR of
      peptide with single (13)C isotopic labeling can be used to probe the
      electrostatic environment of the peptide local structure.

PMID- 18078333
TI  - Highly effective DNA photocleavage by novel "rigid" Ru(bpy)(3)-4-nitro- and -4
      amino-1,8-naphthalimide conjugates.
AB  - The synthesis of the two novel 1,8-naphthalimideruthenium conjugates Ru-Nap-NO(2)
      and Ru-Nap-NH(2) and their photophysical evaluation upon interaction with DNA is
      reported. Significant changes were seen in both the absorption and emission
      spectra upon interaction of both conjugates with DNA, from which large binding
      constants were determined. Moreover, highly efficient DNA cleavage was observed
      upon irradiation for 5 min, during which supercoiled DNA was converted to nicked
      and linear DNA by Ru-Nap-NH(2).

PMID- 18078334
TI  - Lithography inside Cu(OH)2 nanorods: a general route to controllable synthesis of
      the arrays of copper chalcogenide nanotubes with double walls.
AB  - A series of well-aligned arrays of copper chalcogenide nanostructures, including
      Cu(7)S(4) and Cu(2-x)Se nanotubes with double walls have been successfully
      prepared by using Cu(OH)(2) nanorods as sacrificial templates. This new method is
      based on layer-by-layer chemical conversion and inward etching of the sacrificial
      templates, which is essentially a kind of lithography inside the Cu(OH)(2)
      nanorods. The key step of the process involves repeated formation of the copper
      chalcogenide wall and the dissolution of the Cu(OH)(2) core for two consecutive
      cycles. A large difference of the solubility product (Ksp) between the copper
      chalcogenide wall and the Cu(OH)(2) core materials is crucial for the direct
      replacement of one type of anions by the other. Our work provides a novel and
      general approach to the controllable synthesis of the arrays of copper
      chalcogenide nanotubes with double walls and complex hierarchies.

PMID- 18078335
TI  - Interface reaction route to two different kinds of CeO2 nanotubes.
AB  - CeO(2) nanotubes have been synthesized with a simple solid-liquid interface
      reaction route in the absence of any surfactants. Although the basic reaction
      principles are similar, two kinds of nanotubes with completely different
      morphologies and structures can be generated by slightly tuning the
      postprocessing conditions. The first formation involves employing Ce(OH)CO(3)
      nanorods as both the physical and chemical templates, and the other requires
      layered Ce(OH)3 as an anisotropic intermediate species. During this process, NaOH
      and reaction temperature were demonstrated as the key factors responsible for the
      formation of Ce(OH)(3) intermediate and final CeO(2) nanotubes with well-defined
      structures. The structural details were provided by a combination of XRD, SEM,
      TEM, and HRTEM investigations. Catalytic measurement shows that both nanotubes
      are very active for CO oxidation, and at 250 degrees C, the conversion rates of
      CeO(2) nanotubes are 3 times higher than that of the bulk counterpart.

PMID- 18078336
TI  - Preparation of benzyl azide complexes of iridium(III).
AB  - Hydride complexes IrHCl(2)(PiPr(3))P(2) (1) and IrHCl(2)P(3) (2) [P = P(OEt)(3)
      and PPh(OEt)(2)] were prepared by allowing IrHCl(2)(PiPr(3))(2) to react with
      phosphite in refluxing benzene or toluene. Treatment of IrHCl(2)P(3), first with
      HBF(4).Et(2)O and then with an excess of ArCH(2)N(3), afforded benzyl azide
      complexes [IrCl(2)(eta(1)-N(3)CH(2)Ar)P(3)]BPh(4) (3, 4) [Ar = C(6)H(5), 4
      CH(3)C(6)H(4); P = P(OEt)(3), PPh(OEt)(2)]. Azide complexes reacted in CH(2)Cl(2)
      solution, leading to the imine derivative [IrCl(2){eta(1)
      NH=C(H)C(6)H(5)}P(3)]BPh(4) (5). The complexes were characterized by spectroscopy
      and X-ray crystal structure determination of [IrCl(2)(eta(1)
      N(3)CH(2)C(6)H(5)){P(OEt)(3)}(3)]BPh(4) (3a) and [IrCl(2){eta(1)
      NH=C(H)C(6)H(5)}{P(OEt)(3)}(3)]BPh(4) (5a). Both solid-state structure and (15)N
      NMR data indicate that the azide is coordinated through the substituted Ngamma
      [Ir]-Ngamma(CH(2)Ar)NNalpha nitrogen atom.

PMID- 18078337
TI  - Synthesis, characterization, and study of octanuclear iron-oxo clusters
      containing a redox-active Fe4O4-cubane core.
AB  - A one-pot synthetic procedure yields the octanuclear Fe(III) complexes
      Fe(8)(micro(4-)O)(4)(micro-pz(*))(12)X(40, where X = Cl and pz(*) = pyrazolate
      anion (pz = C(3)H(3)N(2)-) (1), 4-Cl-pz (2), and 4-Me-pz (3) or X = Br and pz(*)
      = pz (4). The crystal structures of complexes 1-4, determined by X-ray
      diffraction, show an Fe(4)O(4)-cubane core encapsulated in a shell composed of
      four interwoven Fe(micro-pz(*))(3)X units. Complexes 1-4 have been characterized
      by 1H NMR, infrared, and Raman spectroscopies. Mossbauer spectroscopic analysis
      distinguishes the cubane and outer Fe(III) centers by their different isomer
      shift and quadrupole splitting values. Electrochemical analyses by cyclic
      voltammetry show four consecutive, closely spaced, reversible reduction processes
      for each of the four complexes. Magnetic susceptibility studies, corroborated by
      density functional theory calculations, reveal weak antiferromagnetic coupling
      among the four cubane Fe centers and strong antiferromagnetic coupling between
      cubane and outer Fe atoms of 1. The structural similarity between the
      antiferromagnetic Fe(8)(micro(4-)O)(4) core of 1-4 and the antiferromagnetic
      units contained in the minerals ferrihydrite and maghemite is demonstrated by X
      ray and Mossbauer data.

PMID- 18078338
TI  - Hierarchical self-assembly of aminopyrazole peptides into nanorosettes in water.
AB  - Self-association of aminopyrazole peptide hybrid 1 leads to stacked nanorosettes.
      This remarkable, well-ordered structure obeys the laws of nucleic acid self
      assembly. In a strictly hierarchical process, formation of aminopyrazole "base"
      triplets via a hydrogen bond network is accompanied by pi-stacking with a second
      rosette and final dimerization of two double rosettes to a four-layer
      superstructure, stabilized by a six-fold half-crown alkylammonium lock. The final
      complex is soluble in organic as well as in aqueous solution. It was
      characterized in the solid state by X-ray crystallography, in water by NMR
      spectroscopy, and in silico by quantum chemical shift calculation. All these
      methods provide strong evidence for the same hexameric complex geometry. Its
      structural features bear striking similarity to nucleic acid architectures and
      their peptidic counterparts, especially alanyl-PNA. The whole self-assembly
      process is highly solvent- and temperature-dependent and occurs with a high
      degree of cooperativity--no intermediates are observed. Formation and
      dissociation of the nanorosette, however, are kinetically slow. The limitation to
      a hexameric aggregate can be explained by six sterically demanding valine
      residues, whose replacement by alanines may result in formation of infinite
      fibers.

PMID- 18078340
TI  - Residue-specific radical-directed dissociation of whole proteins in the gas
      phase.
AB  - The rapid identification of proteins from biological samples is critical for
      extracting useful information in proteomics studies. Mass spectrometry is one
      among the various methods of choice for achieving this task; however, current
      approaches are limited by a lack of chemical control over proteins in the gas
      phase. Herein, it is shown that modification of tyrosine to iodo-tyrosine
      followed by UV photodissociation of the carbon-iodine bond can be used to
      generate a radial site specifically at the modified residue. The subsequent
      dissociation of the protein is largely dominated by radical-directed reactions,
      including dominant backbone fragmentation at the modified tyrosine. If iodination
      of the protein is carried out under natively folded conditions, the modification
      and ultimate fragmentation can typically be isolated to a single tyrosine
      residue. Some secondary backbone cleavage in the immediate vicinity of the
      modified tyrosine also occurs, especially if proline is present. In the absence
      of a reactive tyrosine residue, similar chemistry occurs via iodination at
      histidine. Possible mechanisms which would lead to the observed a-type fragments
      at tyrosine and the secondary fragments at proline are discussed. A method for
      using this type of site-specific information to reduce database searching times
      in proteomics experiments by several orders of magnitude is outlined.

PMID- 18078339
TI  - Pyrene excimer signaling molecular beacons for probing nucleic acids.
AB  - Molecular beacon DNA probes, containing 1-4 pyrene monomers on the 5' end and the
      quencher DABCYL on the 3' end, were engineered and employed for real-time probing
      of DNA sequences. In the absence of a target sequence, the multiple-pyrene
      labeled molecular beacons (MBs) assumed a stem-closed conformation resulting in
      quenching of the pyrene excimer fluorescence. In the presence of target, the
      beacons switched to a stem-open conformation, which separated the pyrene label
      from the quencher molecule and generated an excimer emission signal proportional
      to the target concentration. Steady-state fluorescence assays resulted in a
      subnanomolar limit of detection in buffer, whereas time-resolved signaling
      enabled low-nanomolar target detection in cell-growth media. It was found that
      the excimer emission intensity could be scaled by increasing the number of pyrene
      monomers conjugated to the 5' terminal. Each additional pyrene monomer resulted
      in substantial increases in the excimer emission intensities, quantum yields, and
      excited-state lifetimes of the hybridized MBs. The long fluorescence lifetime (
      approximately 40 ns), large Stokes shift (130 nm), and tunable intensity of the
      excimer make this multiple-pyrene moiety a useful alternative to traditional
      fluorophore labeling in nucleic acid probes.

PMID- 18078342
TI  - Lateral diffusion in lipid membranes through collective flows.
AB  - There is no comprehensive model for the dynamics of cellular membranes. Even
      mechanisms of basic dynamic processes, such as lateral diffusion of lipids, are
      poorly understood. Our atomic-scale molecular dynamics simulations support a
      novel, concerted mechanism for lipid diffusion. We find that a lipid and its
      nearest neighbors move in unison, forming loosely defined clusters. What is more,
      the motions of lipids are correlated over tens of nanometers: the lateral
      displacements of lipids in a given monolayer produce striking two-dimensional
      flow patterns. These flow patterns should have wide implications, affecting, for
      example, the formation of membrane domains, protein functionality, and action of
      lipases and drugs on membranes.

PMID- 18078343
TI  - Metal ion induced FRET OFF-ON in tren/dansyl-appended rhodamine.
AB  - A series of new fluorescent probes bearing tren-spaced rhodamine B and dansyl
      groups have been synthesized. Compound 1 exhibits selective changes in the
      absorption and the emission spectra toward Cu2+ ion over miscellaneous metal
      cations. Among 1-3, 1 shows the best FRET efficiency through dansyl emission to
      rhodamine absorption for the Cu2+ ion.

PMID- 18078344
TI  - New cytotoxic 14-membered macrolides from marine-derived fungus Aspergillus
      ostianus.
AB  - Three new 14-membered macrolides, named aspergillides A, B, and C (1, 5, and 7),
      were isolated from marine-derived fungus Aspergillus ostianus strain 01F313,
      cultured in a medium composed of bromine-modified artificial seawater. The
      structures of the new compounds were determined by analyses of 1D and 2D NMR
      spectra. Their absolute configurations were elucidated by the modified Mosher's
      method and chemical conversions. The new compounds showed cytotoxic activity
      against mouse lymphocytic leukemia cells (L1210).

PMID- 18078345
TI  - Expression of secreted His-tagged S-adenosylmethionine synthetase in the
      methylotrophic yeast Pichia pastoris and its characterization, one-step
      purification, and immobilization.
AB  - S-Adenosylmethionine synthetase (SAM synthetase) catalyzes the synthesis of S
      adenosylmethionine (SAM), which plays an important role in cellular functions
      such as methylation, sulfuration, and polyamine synthesis. To develop a simple
      and effective way to enzymatically synthesize and produce SAM, a soluble form of
      SAM synthetase encoded by SAM2 from Saccharomyces cerevisiae was successfully
      produced at high level ( approximately 200 mg/L) by the recombinant
      methylotrophic yeast Pichia pastoris. The secreted His6-tagged SAM synthetase was
      purified in a single chromatography step with a yield of approximately 82% for
      the total activity. The specific activity of the purified synthetase was 23.84
      U/mg. The recombinant SAM synthetase could be a kind of allosteric enzyme with
      negative regulation. The enzyme functioned optimally at a temperature of 35
      degrees C and pH 8.5. The stability of the recombinant synthetase and the
      effectiveness of different factors in preventing the enzyme from inactivation
      were also studied. Additional experiments were performed in which the recombinant
      SAM synthetase was purified and immobilized in one step using immobilized metal
      chelate affinity chromatography. The immobilized synthetase was found to be 40.4%
      of the free enzyme activity in catalyzing the synthesis of SAM from dl-Met and
      ATP.

PMID- 18078346
TI  - Palladium-catalyzed hydrophenylation of alkynes with sodium tetraphenylborate
      under mild conditions.
AB  - In an aqueous solution of acetic acid, PdCl2(PPh3)2 showed high catalytic
      activity for the hydrophenylation of both terminal and internal alkynes with
      sodium tetraphenylborate (NaBPh4) under mild conditions, affording phenyl alkenes
      in moderate to excellent yields.

PMID- 18078347
TI  - A novel palladium-catalyzed dicarbonylation process leading to coumarins.
AB  - A novel approach to coumarin derivatives has been developed starting from readily
      available 2-(1-hydroxyprop-2-ynyl)phenols, based on an unprecedented palladium
      catalyzed dicarbonylation process. Reactions were carried out in the presence of
      catalytic amounts of PdI2 in conjunction with an excess of KI in MeOH as the
      solvent at room temperature and under 90 atm of CO to give 3
      [(methoxycarbonyl)methyl]coumarins in good to high isolated yields (62-87%).

PMID- 18078348
TI  - Infrared studies reveal unique vibrations associated with the PGK-ATP-3-PG
      ternary complex.
AB  - Phosphoglycerate kinase (PGK) catalyzes a reversible phospho-transfer reaction
      between ATP and 3-phosphoglycerate (3-PG) that is thought to require a hinge
      bending motion in the protein that brings two separate substrate-binding domains
      together. We have used difference infrared spectroscopy to better understand the
      conformational changes that are unique to the PGK-ATP-3-PG complex. Caged
      nucleotides (caged-ADP and caged-ATP) were used to initiate nucleotide binding to
      PGK or PGK-3-PG complexes. The difference spectra include those of PGK-ATP minus
      PGK, PGK-3-PG-ATP minus PGK-3-PG, PGK-3-PG-ADP minus PGK-3-PG, and PGK-ADP minus
      PGK. The resulting spectra were compared in attempts to identify bands associated
      with each PGK complex. In addition, complementary activity assays were performed
      in the presence of caged-nucleotides. While PGK activity decreased in the
      presence of caged-ADP, the activity was not influenced by the addition of caged
      ATP. The activity assay results suggest that the caged-ADP may interact with PGK
      substrate binding site(s) and inhibit phospho-transfer. Therefore, additional
      difference infrared nucleotide exchange experiments were used to isolate the
      differences between ADP and ATP binding to PGK. Difference FTIR spectra obtained
      on PGK-nucleotide-3-PG complexes show distinct bands that may result from amino
      acid side chains as well as structural changes in the hinge region and/or
      increased interactions such as salt bridges forming between the two domains. The
      infrared data obtained on the active ternary complexes show evidence of changes
      in alpha-helix and beta-structures as well as signals consistent with Arg, Asn,
      His, Lys, Asp, Glu, and additional side chains that are uniquely perturbed in the
      active ternary complex as compared to other PGK complexes.

PMID- 18078349
TI  - Implication for using heme methyl hyperfine shifts as indicators of heme seating
      as related to stereoselectivity in the catabolism of heme by heme oxygenase: in
      plane heme versus axial his rotation.
AB  - The triple mutant of the solubilized, 265-residue construct of human heme
      oxygenase, K18E/E29K/R183E-hHO, has been shown to redirect the exclusive alpha
      regioselectivity of wild-type hHO to primarily beta,delta-selectivity in the
      cleavage of heme (Wang, J., Evans, J. P., Ogura, H., La Mar, G. N., and Ortiz de
      Montellano, P. R. (2006) Biochemistry 45, 61-73). The 1H NMR hyperfine shift
      pattern for the substrate and axial His CbetaH's and the substrate-protein
      contacts of the cyanide-inhibited protohemin and 2,4-dimethyldeuterohemin
      complexes of the triple mutant have been analyzed in detail and compared to data
      for the WT complex. It is shown that protein contacts for the major solution
      isomers for both substrates in the mutant dictate approximately 90 degrees in
      plane clockwise rotation relative to that in the WT. The conventional
      interpretation of the pattern of substrate methyl hyperfine shifts, however,
      indicates substrate rotations of only approximately 50 degrees . This paradox is
      resolved by demonstrating that the axial His25 imidazole ring also rotates
      counterclockwise with respect to the protein matrix in the mutant relative to
      that in the WT. The axial His25 CbetaH hyperfine shifts are shown to serve as
      independent probes of the imidazole plane orientation relative to the protein
      matrix. The analysis indicates that the pattern of heme methyl hyperfine shifts
      cannot be used alone to determine the in-plane orientation of the substrate as it
      relates to the stereospecificity of heme cleavage, without explicit consideration
      of the orientation of the axial His imidazole plane relative to the protein
      matrix.

PMID- 18078350
TI  - Alzheimer's Abeta peptides containing an isostructural backbone mutation afford
      distinct aggregate morphologies but analogous cytotoxicity. Evidence for a common
      low-abundance toxic structure(s)?
AB  - Amyloid beta (Abeta) peptide amyloidogenesis, involving the formation of numerous
      distinct quaternary structures, appears to cause Alzheimer's disease. However,
      the precise identification of the toxic structure(s) and the neurotoxicity
      mechanism(s) remains elusive. Mutating the Abeta 1-40 Phe19-Phe20 backbone amide
      bond to an isostructural E-olefin bond enables formation of spherical aggregates
      to the exclusion of detectable amyloid fibrils. Herein, the fibrillization and
      toxicity of amide-to-ester mutants of Abeta 1-40 at the 19-20 position and
      surrounding backbone amide bonds are compared to the fibrillization and toxicity
      of the 19-20 E-olefin Abeta analogue and wild type Abeta. Whereas isostructural
      amide-to-E-olefin mutations eliminate both the H-bond donor and acceptor
      capabilities, isostructural amide-to-ester mutations eliminate the donor while
      retaining the ester carbonyl as a weakened acceptor. None of the amide-to-ester
      Abeta 1-40 mutants prevent fibrillization; in fact several exhibit hastened
      amyloidogenesis. The 18-19 amide-to-ester substitution is the only backbone
      mutation within the hydrophobic core region of the fibril (residues 17-21) that
      significantly slows fibrillization. Despite forming different morphologies, the
      19-20 E-olefin mutant, the 18-19 amide-to-ester mutant, and WT Abeta 1-40 fibrils
      all exhibit similar toxicities when applied to PC12 cells at 18 h into the
      aggregation reactions, as assessed by MTT metabolic activity measurements. This
      result suggests that a common but low abundance aggregate morphology, that is
      accessible to these Abeta analogues, mediates toxicity, or that several different
      aggregate morphologies are similarly toxic.

PMID- 18078352
TI  - Genomic signatures associated with the development, progression, and outcome of
      prostate cancer.
AB  - Prostate cancer remains a common cause of cancer death in men. Applications of
      new genomic technologies to the recent development of high-quality prostate
      cancer models in multiple contexts have added great molecular insight into the
      development of and progression to metastasis. Genomic analysis of DNA, RNA, and
      protein alterations allows for the global assessment of this disease and provides
      the molecular framework to improve risk classification, outcome prediction, and
      development of targeted therapies. The creation of expression profiles and
      signatures will allow the evaluation of cancer phenotypes and give insight into
      determining those with increased risk of cancer, identification of critical
      pathways involved in the development of cancer, prediction of disease outcome,
      and assessment of the response of cancer to established and novel therapies. This
      review focuses on highlighting recent work in genomics and on its role in
      evaluating potential genetic modifiers of prostate cancer and novel biomarkers
      that may help with prostate cancer diagnosis, its potential to provide a better
      understanding of prostate cancer behavior and transition to metastatic disease,
      and its role in current and new therapies in prostate cancer. This framework has
      the exciting potential to be predictive and provide personalized and individual
      treatment to the large number of men diagnosed with prostate cancer each year.

PMID- 18078353
TI  - Use of the Oncotype DX 21-gene assay to guide adjuvant decision making in early
      stage breast cancer.
AB  - The decision to use adjuvant chemotherapy in patients with early stage breast
      cancer involves the consideration of many factors that traditionally rely heavily
      on tumor size and lymph node involvement and a limited set of biologic
      characteristics such as estrogen receptor and HER2 expression. Overtreatment with
      cytotoxic chemotherapy is a significant concern among patients and physicians.
      Using the currently accepted guidelines it has been estimated that a large
      percentage of patients receiving chemotherapy for low-risk breast cancers may be
      overtreated. Gene expression profiling is a new technology being developed to
      help improve risk stratification of patients and to predict outcomes. The
      Oncotype DXtrade mark assay is one example of a gene expression profile validated
      in women with lymph node-negative, estrogen receptor-expressing breast cancer.
      This assay and others aim to help improve risk classification and recurrence
      prediction and, therefore, optimize selection of patients for adjuvant
      chemotherapy.

PMID- 18078355
TI  - Newborn screening for adrenoleukodystrophy: implications for therapy.
AB  - X-Linked adrenoleukodystrophy (X-ALD) is a progressive metabolic condition
      affecting the adrenal glands and nervous system of males. Although variable in
      the age of onset and presentation in families, X-ALD does present in
      characteristic phenotypes including a devastating childhood form that affects 35%
      of boys with this genetic condition. The majority of males with X-ALD will also
      develop adrenal insufficiency, which may result in crisis. Early detection is
      desirable in order to prevent morbidity from this condition. We have recently
      developed a tandem mass spectroscopy method that allows this to be done during
      newborn screening for other genetic disorder. In this review, we discuss the
      rationale for early detection, its effect on treatment, and some of the
      uncertainties.

PMID- 18078354
TI  - Cancer pharmacogenomics: role of DNA repair genetic polymorphisms in
      individualizing cancer therapy.
AB  - The evolving field of cancer pharmacogenomics uses genetic profiling to predict
      the response of tumor and normal tissue to therapy. The narrow therapeutic index
      and heterogeneity of patient responses to chemotherapy and radiotherapy implies
      that the efficacy of these treatments could, potentially, be significantly
      enhanced by improving our understanding of the genetic bases for interindividual
      differences in their effects. The cytotoxicity of both chemotherapy and
      radiotherapy is to a large extent directly related to their ability to induce DNA
      damage. The ability of cancer cells to recognize and repair this damage
      contributes to therapeutic resistance. On the other hand, suboptimal DNA repair
      in normal tissue may negatively impact on normal tissue tolerance. More than 130
      genes have been identified that are associated with human DNA repair, and single
      nucleotide polymorphisms of several of the DNA repair genes have been described
      recently. In this article, we present the current evidence implicating variations
      within DNA repair genes as important predictive and prognostic markers in cancer.
      We review evidence suggesting DNA repair genetic polymorphisms may significantly
      influence the clinical response to chemotherapy and radiotherapy, and may
      influence normal tissue tolerance to cancer treatments.

PMID- 18078358
TI  - Introduction: narcolepsy and excessive daytime sleepiness: from the bench to the
      bedside.

PMID- 18078356
TI  - Pharmacogenetic basis for therapeutic optimization in Alzheimer's disease.
AB  - Alzheimer's disease is a major health problem in developed countries.
      Approximately 10-15% of direct costs in dementia are attributed to
      pharmacological treatment, and only 10-20% of the patients are moderate
      responders to conventional antidementia drugs, with questionable cost
      effectiveness. The phenotypic expression of Alzheimer's disease is characterized
      by amyloid deposition in brain tissue and vessels (amyloid angiopathy),
      intracellular neurofibrillary tangle formation, synaptic and dendritic loss, and
      premature neuronal death. Primary pathogenic events underlying this
      neurodegenerative process include genetic factors involving more than 200
      different genes distributed across the human genome, accompanied by progressive
      cerebrovascular dysfunction, and diverse environmental factors. Mutations in
      genes directly associated with the amyloid cascade (APP, PSEN1, PSEN2) are
      present in less than 5% of the Alzheimer's disease population; however, the
      presence of the epsilon4 allele of the apolipoprotein E gene (APOE) represents a
      major risk factor for more than 40% of patients with dementia. Genotype-phenotype
      correlation studies and functional genomics studies have revealed the association
      of specific mutations in primary loci and/or APOE-related polymorphic variants
      with the phenotypic expression of biological traits. It is estimated that
      genetics accounts for between 20% and 95% of the variability in drug disposition
      and pharmacodynamics. Recent studies indicate that the therapeutic response in
      Alzheimer's disease is genotype specific, depending on genes associated with
      Alzheimer's disease pathogenesis and/or genes responsible for drug metabolism
      (e.g. cytochrome P450 [CYP] genes). In monogenic studies, APOEepsilon4/epsilon4
      genotype carriers are the worst responders to conventional treatments. Some
      cholinesterase inhibitors currently being use in the treatment of Alzheimer's
      disease are metabolized via CYP-related enzymes. These drugs can interact with
      many other drugs that are substrates, inhibitors or inducers of the CYP system,
      this interaction eliciting liver toxicity and other adverse drug reactions.
      CYP2D6 enzyme isoforms are involved in the metabolism of more than 20% of drugs
      used in CNS disorders. The distribution of the CYP2D6 genotypes in the European
      population of the Iberian peninsula differentiates four major categories of
      CYP2D6-related metabolizer types: (i) extensive metabolizers (EM) [51.61%]; (ii)
      intermediate metabolizers (IM) [32.26%]; (iii) poor metabolizers (PM) [9.03%];
      and (iv) ultra-rapid metabolizers (UM) [7.10%]. PMs and UMs tend to show higher
      transaminase activity than EMs and IMs. EMs and IMs are the best responders, and
      PMs and UMs are the worst responders to pharmacologic treatments in Alzheimer's
      disease. At this early stage of the development of
      pharmacogenomic/pharmacogenetic procedures in Alzheimer's disease therapeutics,
      it seems very plausible that the pharmacogenetic response in Alzheimer's disease
      depends on the interaction of genes involved in drug metabolism and genes
      associated with Alzheimer's disease pathogenesis.

PMID- 18078359
TI  - Narcolepsy and excessive daytime sleepiness: diagnostic considerations,
      epidemiology, and comorbidities.
AB  - Narcolepsy is a chronic, neurologic disorder that has severe disabling effects on
      affected patients. It usually becomes manifest between the ages of 10 and 25
      years and is recognized by a tetrad of symptoms that includes excessive daytime
      sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Excessive
      daytime sleepiness is common and associated with a broad range of medical, sleep,
      and psychiatric disorders; therefore, accurate diagnosis of narcolepsy and
      comorbid disorders is important for optimal treatment response.

PMID- 18078360
TI  - Narcolepsy: pathophysiology and pharmacology.
AB  - Narcolepsy, which affects 1 in 2000 people in the general population, is
      characterized by excessive daytime sleepiness (EDS), cataplexy, and other
      dissociated manifestations of rapid eye movement sleep (hypnagogic hallucinations
      and sleep paralysis). The disease is currently treated with amphetamine-like
      central nervous system stimulants (for EDS) and antidepressants (for cataplexy).
      Some compounds from other classes, such as modafinil (a non-amphetamine wake
      promoting compound for EDS) and sodium oxybate (a short-acting sedative for EDS
      and cataplexy, administered at night), are also employed. The major
      pathophysiology of human narcolepsy has recently been revealed by the extension
      of discoveries of narcolepsy genes in animal models: hypocretin/orexin ligand
      deficiency has been shown in about 90% of human narcolepsy-cataplexy. This
      finding led directly to the development of new diagnostic tests (i.e.,
      cerebrospinal fluid hypocretin measures). Hypocretin replacement is also likely
      to be a new therapeutic option for hypocretin-deficient narcolepsy, but is still
      not available in humans. In this review, the pharmacologic and pathophysiologic
      aspects of narcolepsy are discussed.

PMID- 18078361
TI  - Narcolepsy: treatment issues.
AB  - Pharmacologic management of patients with narcolepsy is usually based on treating
      the separate symptoms of cataplexy and excessive daytime sleepiness (EDS). For
      treating cataplexy, the most widely used medications include the antidepressants
      venlafaxine, imipramine, and protriptyline, usually at lower doses than
      prescribed with depression, and sodium oxybate. Monoamine oxidase inhibitors are
      also sometimes used, but much less frequently. The U.S. Food and Drug
      Administration has approved 4 medications for EDS: dextroamphetamine,
      methylphenidate, modafinil, and sodium oxybate. Sodium oxybate is the only drug
      approved for treating both cataplexy and EDS. Modafinil and sodium oxybate have
      similar, long-term efficacies in treating EDS at prescribed doses.

PMID- 18078363
TI  - Common ("classical") and covered cloacal exstrophy: a histopathological study and
      a reconstruction of the pathogenesis.
AB  - Current opinion about structure and pathogenesis of cloacal exstrophy was
      challenged by histopathological findings and new insights into the normal
      development. Autopsy specimens of common (n = 3) and covered cloacal exstrophy (n
      = 4) with single intraexstrophic and -perineal phallic structures and perineo
      exstrophic canals have been analyzed histopathologically. The findings were
      correlated to normal development to reconstruct the pathogenesis. By identifying
      a specific cloaca-derived urethra field as distinct from allantois-derived
      bladder fields, the exstrophic area is found to reflect the original hindgut
      configuration in embryos of approximately 26-29 postovulatory days gestational
      age (2-4 mm). Correlation to normal development suggests malfunctioning of the
      primitive streak/caudal eminence as a primary fault that leads to a defective
      cloacal region in the hindgut disturbing cloacal-intestinal-allantoic
      dissociation and also causes lengthening of the intestinal region into a blind
      ending colon, teratoma-like lesions, and vertebral and muscular anomalies. The
      current idea that membranes in "covered cloacal exstrophy" represent persisting
      cloacal membranes is dismissed by finding an amnion-like structure, which
      suggests dysfunction of an umbilical ring placode as a simultaneous 2nd fault.
      This malfunctioning may cause omphalocele by defective demarcation of the
      umbilical cord and may replace midline stroma of the infraumbilical abdominal
      wall by extraembryonic tissue that stretches into a weak temporary membrane, may
      leave a perineo-extrophic canal, and may allow the formation of a single perineal
      or intraexstrophic phallus. Malfunctioning without replacement may result in a
      purely epithelial "allantoic" membrane, which by disintegrating in combination
      with the cloacal membrane will expose common cloacal exstrophy.

PMID- 18078364
TI  - Ependymoblastomatous exencephaly: a unique fetal malformation.
AB  - Exencephaly/anencephaly is a rare neural tube defect occurring early in
      embryogenesis. We report a 14-week-old fetus with exencephaly in whom central
      nervous system tissue was developed and preserved. There were 2 symmetrical
      structures grossly resembling cerebral hemispheres, which on histologic and
      ultrastructural study, consisted of a combination of ependymoblastomatous
      rosettes and canals and primitive neural tissue. The brainstem and spinal cord
      were partially normally formed, although descending tracts were not apparent. No
      cerebellar tissue was found. The eyes were formed. This appears to represent a
      rare example of exencephaly not covered by skin, which did not undergo necrosis
      and early transformation into a residual area cerebrovasculosa, characteristic of
      anencephaly. It may be appropriate to regard this as a unique neural tube closure
      defect that might be termed "ependymoblastomatous exencephaly."

PMID- 18078365
TI  - A family with atypical cystic fibrosis: brother and sister with heterozygosity
      for both G542X and R117H.
AB  - Clinical manifestations of cystic fibrosis (CF) are variable. Genetic and
      environmental factors that determine whether an individual will develop
      associated complications are still under investigation. The present study reports
      the genetic analysis of a family with different clinical forms of CF and
      addresses the difficulty of CF diagnosis in an individual with mutant alleles
      G542X and R117H because of the variable phenotype associated with R117H mutation.
      Both children in this family were heterozygous for G542X/R117H with the same
      thymine sequence (7T/9T) in intron 8 of CF transmembrane conductance regulator.
      The girl was diagnosed with CF, whereas the boy was diagnosed with azoospermia as
      the sole clinical manifestation. The possible implication of the hemochromatosis
      gene as a CF modifier locus was analyzed because the 2 children had the same
      genotype. No genetic differences were detected between brother and sister that
      explained the different clinical manifestations of CF.

PMID- 18078366
TI  - Beta-catenin mutations do not contribute to cardiac fibroma pathogenesis.
AB  - Cardiac fibromas are the 2nd most common benign cardiac tumor occurring in
      children and bear a striking morphologic resemblance to soft tissue or desmoid
      fibromatosis. Since activating mutations in beta-catenin are common in desmoid
      fibromatosis as well as other spindle cell proliferations, the aim of our study
      was to determine if such mutations could be identified in cardiac fibroma. Nine
      cardiac fibromas from patients with surgical resection were examined for beta
      catenin mutations by immunoperoxidase staining for beta-catenin protein and DNA
      sequencing of a region in exon 3 of the beta-catenin gene, where relatively
      conserved mutations have been described in desmoid fibromatosis. The mean age of
      the patients was 7.6 years (range: 10 weeks to 27 years), and 6 of the patients
      were male. No nuclear staining for beta-catenin was seen in the fibroma cells by
      immunoperoxidase methods. The beta-catenin exon 3 sequence data showed no
      mutations in any of the 9 tumors. We conclude that despite their morphologic
      similarity, cardiac fibroma and desmoid fibromatosis do not share this common
      molecular pathway of neoplastic growth.

PMID- 18078367
TI  - Expression of transforming growth factor-beta 1, -beta 2, and -beta 3 in human
      developing teeth: immunolocalization according to the odontogenesis phases.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor
      that has several biological effects in vivo, including control of cell growth and
      differentiation, cell migration, lineage determination, motility, adhesion,
      apoptosis, and synthesis and degradation of extracellular matrix, and TGF-beta
      plays an important role in regulating tissue repair and regeneration. Our study
      analyzed the participation of TGF-beta 1, -beta 2, and -beta 3 in the different
      stages of morphogenesis and differentiation of human developing dental organ
      using immunohistochemistry. The maxillae and mandibles of 10 human embryos
      ranging from 8 to 23 weeks of gestation were employed, according to the approval
      of the ethical committee. Our study revealed that the TGF-beta subunits-beta 1,
      beta 2, and beta 3-were present in the various stages of tooth development, but
      the expression varied according to the differentiation stage, tissue, and TGF
      beta subunit. Our results indicated that TGF-beta 1 is closely related to
      differentiation of enamel organ and initiation of matrix secretion, TGF-beta 2 to
      cellular differentiation, and TGF-beta 3 to mineral maturation matrix.

PMID- 18078368
TI  - Umbilical polyp in an infant.

PMID- 18078369
TI  - Variability of acetylcholinesterase hyperinnervation patterns in distal rectal
      suction biopsy specimens in Hirschsprung disease.
AB  - Variability in cholinergic innervation may contribute to false-negative and false
      positive evaluations for Hirschsprung disease (HD). We compared intraspecimen
      variability of histochemical acetylcholinesterase (ACE) activity in 62 distal
      rectal mucosal biopsy specimens from 33 patients with short-segment HD (SSHD), 14
      patients with short-segment HD/Down syndrome (SSHD/DS), 10 patients with total
      colonic aganglionosis (HDTC), and 45 ganglionated control specimens obtained
      because of clinical suspicion for HD. Specimens were evaluated in 1-mm linear
      segments for abnormal distribution and abnormal intensity of staining reaction in
      the lamina propria (LP), muscularis mucosae (MM), numerical excess of small
      submucosal nerves (SSN), and presence or absence of large submucosal nerves (LSN)
      defined as >35 microns in diameter. Patients with HD and controls were
      predominantly infant males. Aggregate length of specimens was 186 mm in HD and
      136 mm in controls. We defined multiple patterns and relative frequencies of
      normal and abnormal ACE reactivity in the muscularis mucosae, submucosal nerves,
      and innervation in the lamina propria. We verified a hyperinnervation pattern
      more common in neonates within each subset of HD. Large submucosal nerves >35
      microns in diameter are relatively less common in SSHD/DS and HDTC. Eleven of 57
      patients with HD had at least 1 mm of normal muscularis mucosae accounting for
      19/186 mm examined. Ten percent of control mm had at least 1 submucosal nerve >35
      microns in diameter. Intraspecimen variability in ACE patterns, when extreme, can
      usually be resolved by findings elsewhere in an adequate specimen, minimizing the
      need for repeat procedures.

PMID- 18078379
TI  - High-throughput screen for small molecule inhibitors of Mint1-PDZ domains.
AB  - Several hundred PDZ (postsynaptic density-95, Drosophila disks-large, ZO-1)
      domain-containing proteins have been identified in the human genome. PDZ domains
      play a critical role in organization and function of cellular signaling pathways.
      Thus, small molecule inhibitors of PDZ domain association with their targets have
      wide potential applications as research and therapeutic agents. PDZ domains
      typically bind to a carboxyl-terminal tail of the target protein. Here we
      describe a high-throughput screening (HTS) assay for small molecule inhibitors of
      association between Mint1-PDZ domains and N-type Ca2+ channel carboxyl-terminal
      peptide (NC peptide). The performance of a homogeneous time-resolved fluorescence
      resonance energy transfer (HTRF) and an amplified luminescent proximity
      homogeneous assay (ALPHA) were systematically compared in parallel pilot HTS
      experiments with glutathione S-transferase-Mint1-PDZ1/2 protein and biotinylated
      NC peptide. Both of the two assays showed similar sensitivities in our target
      protein assay. Using HTRF-based assay we screened a library of 100,000 small
      molecule compounds and identified a number of potential "hits." The activity of
      isolated "hits" was confirmed by ALPHA assay. However, further evaluation
      revealed that isolated "hits" most likely act as "promiscuous binders," not as
      specific Mint-PDZ inhibitors, and that additional screening will be required to
      identify the true Mint-PDZ inhibitors. The assays described provided an example
      of HTS for a small molecule inhibitor of Mint-PDZ domain that can be easily
      adapted to other PDZ domain-mediated interactions.

PMID- 18078380
TI  - Cellular HTS assays for pharmacological characterization of Na(V)1.7 modulators.
AB  - Ion channels are challenging targets in the early phases of the drug discovery
      process, especially because of the lack of technologies available to screen large
      numbers of compounds in functionally relevant assays. The electrophysiological
      patch-clamp technique, which is the gold standard for studying ion channels, has
      low throughput and is not amenable to screening large numbers of compounds.
      However, for random high-throughput screening (HTS) of compounds against ion
      channel targets, a number of functional cellular assays have become available
      during the last few years. Here we use the sodium channel NaV1.7 stably expressed
      in human embryonic kidney 293 cells and compare three HTS assays-a Li flux atomic
      absorption spectroscopy (AAS) assay, a fluorescent imaging plate reader (FLIP,
      Molecular Devices, Sunnyvale, CA) membrane potential assay, and a fluorescence
      resonance energy transfer (FRET)-based membrane potential assay-to an automated
      electrophysiological assay (the Ionworks HT [Molecular Devices] platform) and
      characterize 11 known NaV inhibitors. Our results show that all three HTS assays
      are suitable for identification of NaV1.7 inhibitors, but as an HTS assay the Li
      AAS assay is more robust with higher Z' values than the FLIPR and FRET-based
      membrane potential assays. Furthermore, there was a better correlation between
      the Ionworks assay and the Li-AAS assay regarding the potency of the NaV
      inhibitors investigated. This paper describes the first comparison between all
      the HTS assays available today to study voltage-gated NaVs, and the results
      suggest that the Li-AAS assay is more suited as a first HTS assay when starting
      an NaV drug discovery campaign.

PMID- 18078381
TI  - Evaluation of micro-parallel liquid chromatography as a method for HTS-coupled
      actives verification.
AB  - The identification of biologically active compounds from high-throughput
      screening (HTS) can involve considerable postscreening analysis to verify the
      nature of the sample activity. In this study we evaluated the performance of
      micro-parallel liquid chromatography (microPLC) as a separation-based enzyme
      assay platform for follow-up of compound activities found in quantitative HTS of
      two different targets, a hydrolase and an oxidoreductase. In an effort to couple
      secondary analysis to primary screening we explored the application of microPLC
      immediately after a primary screen. In microPLC, up to 24 samples can be loaded
      and analyzed simultaneously via high-performance liquid chromatography within a
      specially designed cartridge. In a proof-of-concept experiment for screen-coupled
      actives verification, we identified, selected, and consolidated the contents of
      "active" wells from a 1,536-well format HTS experiment into a 384-well plate and
      subsequently analyzed these samples by a 24-channel microPLC system. The method
      utilized 0.6% of the original 6-microl 1,536-well assay for the analysis. The
      analysis revealed several non-biological-based "positive" samples. The main
      examples included "false" enzyme activators resulting from an increase in well
      fluorescence due to fluorescent compound or impurity. The microPLC analysis also
      provided a verification of the activity of two activators of glucocerebrosidase.
      We discuss the benefits of microPLC and its limitations from the standpoint of
      ease of use and integration into a seamless postscreen workflow.

PMID- 18078382
TI  - An SMA project report: neural cell-based assays derived from human embryonic stem
      cells.
AB  - Human embryonic stem (ES) cells are promising resources for developing new
      treatments for neurodegenerative diseases. Spinal muscular atrophy (SMA) is one
      of the leading causes of childhood paralysis and infant mortality. SMA is caused
      by inactivation of the survival motor neuron-1 (SMN1) gene. The nearly identical
      SMN2 gene contains a silent polymorphism that disrupts splicing and as a result
      cannot compensate for loss of SMN1. The SMA Project was established by the
      National Institute of Neurological Disorders and Stroke (NINDS) as a pilot effort
      to establish a fully transparent coalition between academics, industry, and
      government to create a centralized network of shared resources and information to
      identify and test new SMA therapeutics. As one of the funded projects, the work
      described here tested the feasibility of generating a SMA cell-based assay using
      neural lineages derived from human ES cells approved for National Institutes of
      Health (NIH)-funded research. Minigene cassettes were constructed, employing
      firefly luciferase or green fluorescent protein (GFP) as reporters for splicing
      efficiency of SMN1 and/or SMN2 under the control of the SMN1, SMN2, or
      cytomegalovirus (CMV) promoters. Transient transfection of proliferating
      neuroprogenitors in a 96-well format with plasmid DNA or adenoviral vectors
      showed differential levels that correlated with the splicing minigene and the
      promoter used; luciferase activities with SMN1 splicing minigenes were higher
      than SMN2, and the CMV promoter generated higher levels of activity than the SMN1
      and SMN2 promoters. Our results indicate that human ES cell-derived
      neuroprogenitors provide a promising new primary cell source for assays of new
      therapeutics for neurodegenerative diseases.

PMID- 18078383
TI  - HIV-1 VprB and C RNA cleavage by potent 10-23 DNAzymes that also cause reversal
      of G2 cell cycle arrest mediated by Vpr genes.
AB  - Accessory Vpr protein of HIV-1 is known to influence several key cellular
      functions that also impacts on the HIV-1 replication cycle. Besides other
      activities, it alone causes cell cycle arrest at the G2 phase and thus
      potentially contribute to the overall pathology. We designed several 10-23
      catalytic motifs containing DNAzymes (Dzs) against the full-length Vpr gene from
      subtype B and checked its activity against VprC gene from one of the Indian HIV-1
      isolates. Among several Dzs that showed sequence-specific cleavage activities, Dz
      94 was very potent and equally efficient in its ability to cleave full-length
      VprB and C RNA to completion under standard conditions of cleavage. Although Dz
      90 target sequence was fully conserved between VprB and C genes, it was more
      effective on latter genes, suggesting that spatial structures of RNA at other
      regions of Vpr can also influence the cleavage activity for this Dz. HIV-1 VprB
      and C encoding genes under the powerful CMV promoter, when cotransfected into
      mammalian cells with Dz-94, a potent intracellular inhibition, was observed,
      which also resulted in reversing the G2 cell cycle arrest mediated by VprB and C
      proteins. Thus, Dz-94 could potentially be developed to prevent Vpr-mediated
      cytopathic effects caused by HIV-1 subtype B and C isolates.

PMID- 18078384
TI  - Protein translocation across the bacterial cytoplasmic membrane.
AB  - About 25% to 30% of the bacterial proteins function in the cell envelope or
      outside of the cell. These proteins are synthesized in the cytosol, and the vast
      majority is recognized as a ribosome-bound nascent chain by the signal
      recognition particle (SRP) or by the secretion-dedicated chaperone SecB.
      Subsequently, they are targeted to the Sec translocase in the cytoplasmic
      membrane, a multimeric membrane protein complex composed of a highly conserved
      protein-conducting channel, SecYEG, and a peripherally bound ribosome or ATP
      dependent motor protein SecA. The Sec translocase mediates the translocation of
      proteins across the membrane and the insertion of membrane proteins into the
      cytoplasmic membrane. Translocation requires the energy sources of ATP and the
      proton motive force (PMF) while the membrane protein insertion is coupled to
      polypeptide chain elongation at the ribosome. This review summarizes the present
      knowledge of the mechanism and structure of the Sec translocase, with a special
      emphasis on unresolved questions and topics of current research.

PMID- 18078385
TI  - Enhanced expression and activation of pro-inflammatory transcription factors
      distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated
      inflammatory responses prevail in the human aneurysm.
AB  - Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic
      aneurysm); however, the nature of the inflammatory factors and cellular
      response(s) involved in AAA growth is controversial. In the present study, we set
      out to determine the aortic levels of inflammatory cytokines in relation to
      downstream inflammatory transcription factors and cellular responses. A
      comparison of AAA wall samples with atherosclerotic wall samples taken from the
      same aortic region allowed AAA-specific inflammatory parameters to be identified
      that distinguish AAAs from ASD (aortic atherosclerotic disease). RT-PCR (real
      time PCR), ELISA, Western blotting and immunohistochemistry were combined to
      assess cytokines and transcription factors at the mRNA and protein level, and
      their activation status. Compared with ASD, inflammatory parameters associated
      with Th1-type [T-bet, IL (interleukin)-2, IFN-gamma (interferon-gamma), TNF-alpha
      (tumour necrosis factor-alpha), IL-1alpha and cytotoxic T-cells] and Th2-type
      [GATA3, IL-4, IL-10, IL-13 and B-cells] responses were all increased in AAA
      samples. Evaluation of major downstream inflammatory transcription factors
      revealed higher baseline levels of C/EBP (CCAAT/enhancer-binding protein) alpha,
      beta and delta in the AAA samples. Baseline p65 NF-kappaB (nuclear factor kappaB)
      and c-Jun [AP-1 (activator protein-1)] levels were comparable, but their
      activated forms were strongly increased in the AAA samples. Downstream target
      genes of p65 NF-kappaB, c-Jun, IL-6 and IL-8 were hyperexpressed. Molecular and
      cellular processes associated with IL-6 and IL-8 hyperactivation were enhanced in
      the AAA samples, i.e. the expression of phospho-STAT-3 (signal transducer and
      activator of transcription-3) and perforin were elevated, and the content of
      plasma cells, neutrophils and vasa vasorum was increased. In conclusion, our
      findings demonstrate that an AAA is a general inflammatory condition which is
      characterized by enhanced expression and activation of pro-inflammatory
      transcription factors, accompanied by IL-6 and IL-8 hyperexpression and
      exaggerated downstream cellular responses, which together clearly distinguish an
      AAA from ASD.

PMID- 18078386
TI  - Angiopoietin-1 gene transfer improves impaired wound healing in genetically
      diabetic mice without increasing VEGF expression.
AB  - Ang-1 (angiopoietin-1) improves the ineffective angiogenesis and impaired wound
      healing in diabetes; however, the mechanism underlying this positive effect is
      still far from being completely understood. In the present study, we investigated
      whether rAAV (recombinant adeno-associated virus)-Ang-1 gene transfer could
      improve wound repair in genetically diabetic mice (db+/db+) and the mechanism(s)
      by which it causes new vessel formation. An incisional skin-wound model in
      diabetic and normoglycaemic mice was used. After the incision, animals received
      rAAV-LacZ or rAAV-Ang-1 in the wound edge. After 7 and 14 days, wounds were used
      to (i) confirm Ang-1 gene transfer, (ii) assess histologically the healing
      process, (iii) evaluate wound-breaking strength, and (iv) study new vessel
      formation by PECAM-1 (platelet/endothelial cell adhesion molecule-1)
      immunostaining. Finally, we investigated VEGF (vascular endothelial growth
      factor) mRNA and protein levels, eNOS (endothelial NO synthase) expression and
      VEGFR-1 and VEGFR-2 (VEGF receptor-1 and -2 respectively) immunostaining. The
      efficiency of Ang-1 gene transfer was confirmed by increased mRNA and protein
      expression of the protein. rAAV-Ang-1 significantly improved the healing process,
      stimulating re-epithelization and collagen maturation, increasing breaking
      strength and significantly augmenting the number of new vessels, as indicated by
      PECAM-1 immunostaining. However, Ang-1 gene transfer did not modify the decrease
      in VEGF mRNA and protein expression in diabetic mice; in contrast, Ang-1
      increased eNOS expression and augmented nitrate wound content and VEGFR-2
      immunostaining and protein expression. Ang-1 gene transfer did not change
      vascular permeability. Similar results were obtained in normoglycaemic animals.
      In conclusion, our results provide strong evidence that Ang-1 gene transfer
      improves the delayed wound repair in diabetes by inducing angiogenesis in a VEGF
      independent manner.

PMID- 18078387
TI  - New targets for pulmonary hypertension: gene and stem cell therapy.

PMID- 18078388
TI  - Lung transplantation for pulmonary hypertension.
AB  - Lung transplantation is an accepted therapeutic intervention for patients with
      pulmonary arterial hypertension (PAH) who fail medical therapy. Highly selected
      candidates with PAH may enjoy improved survival by combining medical therapy with
      transplantation. Despite the known benefits of lung transplantation that include
      improvement in haemodynamics, exercise tolerance, shortness of breath and long
      term survival, this intervention is associated with significant shortcomings.
      These include, the need for lifelong immunosuppression, and the morbidity
      associated with the increased risk for infection and allograft rejection. To
      maximise the potential outcomes of lung transplantation, candidates should be
      selected based on the international guidelines developed by a consensus panel of
      experts in the field (J Heart Lung Transplant, 25, 2006, 745). Early referral to
      a centre with expertise in the management of PAH and transplantation increases
      the chances of achieving the best possible long-term outcome for patients with
      this devastating disease.

PMID- 18078389
TI  - The nurse specialist and practical issues in the care of pulmonary arterial
      hypertension patients.
AB  - Pulmonary arterial hypertension (PAH) remains a devastating disease. All current
      medical therapy is expensive, complex and largely palliative. The management of
      PAH patients requires co-ordination between the patient, their support system,
      third party payers and healthcare professionals. The nurse specialist serves to
      organise these entities, balancing the needs of the patient and the PAH
      programme. The care of the PAH patient requires equal attention to avoiding
      potentially harmful procedures and medications, maximising conventional therapy
      and utilisation of new PAH-specific medical treatment.

PMID- 18078390
TI  - Lessons from oncology to understand and treat pulmonary hypertension.
AB  - Pulmonary artery hypertension (PAH) is now considered to be a proliferative
      disorder characterised by unexplained proliferation of pulmonary artery smooth
      muscle cells (PA-SMCs) and pulmonary artery endothelial cells (PA-ECs). An
      abnormal phenotype of PA-SMCs and PA-ECs has been described in PAH and some
      analogies now appear between pulmonary vascular cells from patients with PAH and
      cancer cells. Such analogies are discussed here with respect to essential
      hallmarks of cancer cells and with the hope that new treatments targeted at one
      or more of these cancer cell abnormalities may be appropriate for PAH.

PMID- 18078391
TI  - From endothelial progenitor cells to vascular remodelling and more: 6 months in
      pulmonary hypertension.

PMID- 18078392
TI  - Diagnosis and treatment of von Willebrand disease: new perspectives and nuances.

PMID- 18078393
TI  - Highly purified VWF/FVIII concentrates in the treatment and prophylaxis of von
      Willebrand disease: the PRO. WILL Study.
AB  - Two therapeutic approaches are available to manage patients with von Willebrand
      disease (VWD): (i) the release of endogenous von Willebrand factor (VWF) from
      endothelial compartments induced by desmopressin (DDAVP); (ii) the transfusion of
      exogenous VWF contained in VWF/FVIII plasma-derived concentrates. Only a few high
      purity VWF/FVIII concentrates have been extensively evaluated in pharmacokinetic
      (PK) trials as well as in retrospective or prospective efficacy studies in VWD.
      The Alphanate Study Group published results of PK and clinical efficacy studies
      in 2002. Efficacy results showed that 75% of bleeding episodes were controlled
      with one or two infusions, and 71% of patients who received prophylactic
      treatment for surgeries or invasive procedures had good clinical responses. In
      another retrospective study, 22 VWD patients in Italy received Fanhdi, a VWF
      concentrate similar to Alphanate. Excellent-good clinical responses were seen in
      92% of bleeding episodes and in 93% of surgical procedures. More recently, the
      efficacy and safety of Fanhdi have been evaluated retrospectively in a larger
      cohort of Italian patients (n = 103) with 97% (bleedings) and 99% (surgeries) of
      excellent/good clinical responses. The largest experience on secondary
      prophylaxis in VWD has been collected in Sweden in 35 patients with severe forms
      of VWD. Secondary prophylaxis was also implemented in a cohort of Italian
      patients with VWD. Prophylaxis was started because of GI bleeds in seven patients
      with types 3 (n = 1), 2A (n = 4), 2M (n = 1) and type 1 (n = 1) and for joint
      bleeds in four patients with type 3 VWD (n = 4). Prophylaxis prevented bleeding
      completely in eight patients and largely reduced hospitalization for blood
      transfusions in the remaining three. The cost-effectiveness of these prophylaxis
      regimens versus on demand therapy will be now investigated in one large
      prospective study (PRO.WILL) organized in Italy.

PMID- 18078394
TI  - Fanhdi, efficacy and safety in von Willebrand's disease: prospective
      international study results.
AB  - Recently, three multicentre prospective international studies have been carried
      out to evaluate the clinical efficacy and safety of Fanhdi [high-purity, double
      inactivated plasma-derived factor VIII/von Willebrand factor (VWF) concentrate]
      in patients with von Willebrand's disease (VWD). Pharmacokinetic parameters,
      clinical efficacy and safety of Fanhdi in acute bleedings episodes or invasive
      procedures were determined in this population. RESULTS: Pharmacokinetic
      parameters observed were similar to previous reported for other highly purified
      plasma-derived FVIII/VWF concentrate. The mean in vivo recovery (IU dL(-1) per IU
      kg(-1)) was 1.9 +/- 0.6 for VWF:RCof; 2.1 +/- 0.6 for VWF:Ag and 2.6 +/- 0.6 for
      FVIII:C. The mean half-life (h) was 14.4 +/- 10.5 for VWF:RCof; 27.5 +/- 11.0 for
      VWF:Ag and 33.4 +/- 16.4 for FVIII:C. Therapeutic benefit of Fanhdi in VWD
      patients treated during bleeding episodes was clearly demonstrated. The
      achievement of haemostasis was excellent or good in 100% of the cases (major or
      minor bleeding episodes). Also, the clinical efficacy of Fanhdi in preventing
      excessive bleeding during surgery showed a very good profile. Efficacy was rated
      as excellent in six cases (three major/three minor surgical procedures) and good
      in three cases (two major/one minor surgical procedures). In addition, the
      product was well tolerated and no adverse events potentially related to the study
      drug were reported. CONCLUSIONS: Fanhdi is an effective and safe plasma-derived
      FVIII/VWF concentrate that can be used as an alternative to the current
      replacement therapy in patients with VWD to provide an adequate haemostasis
      during surgical procedures and treatment of bleeding episodes.

PMID- 18078395
TI  - Creutzfeldt-Jakob disease: reflections on the risk from blood product therapy.
AB  - Creutzfeldt-Jakob disease (CJD) was first described as a clinical entity in the
      1920s, first transmitted experimentally in 1968, and first transmitted
      iatrogenically in 1972 (corneal transplant). Numerous experimental studies in
      rodents, sheep and primates have since revealed very low levels of infectivity in
      blood (about 1/100 000th the level in brain tissue) that can appear as early as
      half-way through the incubation period, with 5-10 fold higher concentrations in
      leucocytes than plasma. Transfused blood from individuals incubating the variant
      form of CJD has transmitted infection to four recipients in the United Kingdom,
      and several dozen other recipients remain at risk. Plasma and plasma proteins
      have not been implicated in any transmissions, and no instance of transmission
      from the blood of individuals incubating other forms of CJD has been recognized.
      Strategies to prevent iatrogenic transmissions include low-risk sourcing,
      leucodepletion, and a variety of infectivity-reducing plasma processing steps;
      screening tests to detect infection in preclinical donors are under development.

PMID- 18078396
TI  - Safety procedures of coagulation factors.
AB  - Two main types of safety procedures must be applied to biological products,
      including plasma derivatives: (i) preventive procedures and (ii) elimination
      procedures. Prevention includes epidemiological control of donor populations;
      checks on each donor's health condition; analysis of each donation for the main
      pathogens using serological methods; additional analysis of all plasma for human
      immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV),
      hepatitis A virus (HAV) and the B19 virus, using nucleic acid amplification
      techniques (NAT). A 60 days or longer inventory hold of all plasma donations is
      applied, to allow additional time to discard previous donations from potential
      seroconverting or otherwise rejectable donors. Elimination procedures minimize
      the low residual risk of transmitting pathogens, including unknown or previously
      undetected ones. Since the introduction 20 years ago of solvent-detergent
      treatment, very effective against enveloped viruses (HIV, HBV, HCV, West Nile
      virus, SARS, avian influenza virus etc), there have been no known cases of
      transmission of this type of pathogens by products manufactured according to this
      procedure. Other inactivation procedures such as pasteurization, dry-heat or
      nanofiltration may prove equally effective. In addition, dry-heat treatment and
      nanofiltration are capable of effectively eliminating non-enveloped viruses (HAV,
      B19 virus). Recent studies show that the B19 virus is much more sensitive to heat
      (in lyophilized state or by pasteurization) and acid pH than previously thought.
      Although there is no evidence for the transmission of classic transmissible
      spongiform encephalopathies (TSEs) through blood or blood-products transfusion,
      four possible cases have been reported in the United Kingdom involving
      transmission by non-leukoreduced blood components of the agent that causes
      variant Creutzfeldt-Jakob Disease (vCJD), a disease linked to the outbreak of
      bovine spongiform encephalopathy (BSE) which took place in that country. However,
      there are no cases of human TSE (classic or variant) transmission by plasma
      derived products. Analytical methods capable of detecting the vCJD agent in
      patients' brains (where high titres are found) and other tissues (such as the
      spleen, appendix and lymph nodes, where much lower concentrations are found) are
      unable to detect the agent in blood or plasma from patients with vCJD, even in
      the clinical phase of the disease. Experiments by Grifols and other groups show
      that the capacity of the production processes to eliminate vCJD agent models is
      many orders of magnitude greater than the maximum expected load of the agent. In
      this regard, the efficacy of precipitation, affinity chromatography, depth
      filtration and nanofiltration are particularly notable.

PMID- 18078397
TI  - Inhibitor development in haemophilia A: the role of von Willebrand factor/factor
      VIII concentrates.
AB  - The presence of inhibitors that neutralize the function of factor VIII (FVIII)
      decreases the haemostatic efficacy of replacement clotting factor concentrate and
      increases morbidity among patients with haemophilia A. Certain genetic and
      environmental variables have been linked to a higher incidence of inhibitors.
      Conversely, the presence of von Willebrand factor (VWF) in some plasma-derived
      FVIII products may provide some measure of protection against inhibitor
      development, although the evidence is not conclusive. Clinical trials are needed
      to resolve this issue and determine the appropriate role of VWF-containing FVIII
      concentrates in the treatment of haemophilia A patients.

PMID- 18078398
TI  - Inhibitors in haemophilia A: current management and open issues.
AB  - The incidence of inhibitors in haemophilia A is 21-33%. The development of
      inhibitors to factor VIII (FVIII) is one of the most serious complications in
      haemophilia therapy and is an important challenge in haemophilia care. The main
      short-term objective of the treatment of haemophilic patients with inhibitors is
      to control bleeding episodes, and the long-term one is to eradicate the inhibitor
      by means of immune tolerance induction (ITI). The choice of treatment for
      bleeding in inhibitor patients is dictated by the current inhibitor titre, the
      severity of the bleed and the previous anamnesic response to FVIII. In low
      responder inhibitor patients the best treatment is large doses of concentrates of
      FVIII to attain haemostatic levels of the factor infused. The same approach can
      also be considered in high responders who have a temporarily low inhibitor level
      and major haemorrhage. High responders patients with high inhibitors titre or
      with minor haemorrhage must be treated with bypassing agents, such as FEIBA
      (factor VIII inhibitor bypassing activity) or recombinant activated FVII (rVIIa);
      there is no agreement which of both agents should be chosen in the different
      clinical situations. Only in patients waiting to start ITI treatment the rFVIIa
      use is clearly recommended, in order to avoide an anamnesic responce. In case of
      failure with this agents, extracorporeal immunoadsortion may be considered. All
      haemophiliac children who develop an inhibitor should be considered for ITI. The
      start of ITI should be deferred until the inhibitor has declined below 10
      Bethesda units/mL (BU ml(-1)) where possible. Starting the treatment when
      inhibitor titre is below 10 BU ml(-1) is the strongest predictor of success.
      However, there are many other points to clarify: recommended FVIII doses in the
      ITI; if the results can be affected by concomitant infections during ITI; if
      there are any differences using plasma derived or recombinant concentrates, even
      more if the plasma-derived concentrate contains large amounts von willebrand
      factor or not; age of starting the ITI and the delay in beginning it; if using
      immunosupresors can help in the treatment of patients with a bad prognosis; and
      when the treatment must be left in patients without a clear failure.

PMID- 18078399
TI  - Factor VIII inhibitors: role of von Willebrand factor on the uptake of factor
      VIII by dendritic cells.
AB  - In patients with haemophilia A, factor VIII (FVIII) therapy leads to the
      development of anti-FVIII alloantibodies that inhibit FVIII pro-coagulant
      activity, in up to 25% of the cases. At a time when efficient viral screening
      procedures are at place, development of inhibitors poses the greatest threat to
      haemophilia A patients. Various risk factors, both patient and product-related,
      are responsible for the development of inhibitory antibodies. The role of FVIII
      specific CD4+ T lymphocytes in the initiation of the humoral immune response to
      exogenous FVIII has been well. In view of their capacity to stimulate naive T
      cells, dendritic cells (DCs) play a central role in the initiation of the primary
      immune response. Thus, in the context of a primary alloimmunization against
      FVIII, i.e. when FVIII-specific B lymphocytes are not there to take up FVIII from
      the circulation and to serve as antigen presenting cells (APCs), DCs are the only
      cell type that internalize FVIII, leading to activation of FVIII-specific CD4+ T
      lymphocytes. von Willebrand factor (VWF) present in plasma-derived FVIII
      therapeutic concentrates, is known to act as a chaperone molecule for
      procoagulant FVIII. In addition to its role in reducing the 'antigenicity' of
      FVIII, the role of VWF in the reduction of the 'immunogenicity' of therapeutic
      FVIII in patients with haemophilia A has also been suggested. We have recently
      demonstrated that VWF protects FVIII from being endocytosed by human DCs and
      subsequently being presented to FVIII-specific T cells. We propose that VWF may
      reduce the immunogenicity of FVIII by preventing, upstream from the activation of
      immune effectors, the entry of FVIII in professional antigen presenting cells.

PMID- 18078400
TI  - Factor VIII products and inhibitor development: the SIPPET study (survey of
      inhibitors in plasma-product exposed toddlers).

PMID- 18078401
TI  - VWF/FVIII complex and the management of patient with inhibitors: from laboratory
      to clinical practice.
AB  - We and others have previously shown that inhibitor containing plasma from
      patients with congenital haemophilia A sometimes reacts less with von Willebrand
      factor (VWF) containing concentrates compared with highly purified plasma-derived
      or recombinant factor VIII (FVIII) concentrates. To further substantiate the
      haemostatic role of a variation in inhibitor reactivity with different FVIII
      concentrates, we compared the inhibitor titres from 11 plasma samples against a
      panel of FVIII concentrates and correlated titre with the capacity to inhibit
      thrombin generation. Three plasma-derived concentrates were tested: Fandhi
      (Grifols) which contains VWF with a final ratio of approximately 1 (VWF IU per IU
      FVIII:C); Haemate (CSL Behring) with a ratio of 2.5 and Haemofil M (Baxter), a
      monoclonal antibody-purified concentrate containing only trace amounts of VWF. In
      addition, the recombinant FVIII concentrate Kogenate Bayer (Bayer) containing no
      VWF was included in the panel. A statistically significant difference in measured
      titres against the four concentrates was found. The inhibitor titre needed to
      inhibit 50% maximum thrombin generation was lowest for Kogenate Bayer and highest
      and similar for Fandhi and Haemate. This study confirms the results from previous
      research regarding variation of inhibitor reactivity against different
      concentrates and further shows that the VWF containing concentrates Fandhi and
      Haemate added to FVIII-deficient plasma with the presence of inhibitor generate
      more thrombin than do the purified concentrates Haemofil M and Kogenate Bayer. A
      further interesting aspect could be that bypass therapy may have an increased
      efficacy when infused together with FVIII concentrates containing VWF. However,
      the clinical implications of all these findings in vitro need to be established.

PMID- 18078402
TI  - VWF/FVIII concentrates in high-risk immunotolerance: the RESIST study.
AB  - Immune tolerance induction (ITI), through the regular infusion of coagulation
      factor concentrates over a time period ranging from 1 to more than 24 months, is
      successful in about 75% of high responders. Among the issues of ITI treatment
      that are still open, the choice of the product to use is one of the most
      difficult. In fact, common practice is to start with the same product that
      induced the inhibitory response, but recent findings indicated that plasma
      derived products containing large amounts of von Willebrand factor (VWF) can play
      a positive role. Two retrospective cohorts in Germany and in France and one
      prospective cohort have shown a high rate of success when VWF/factor VIII (FVIII)
      products are used to induce ITI. For these reasons, two prospective studies have
      been planned to complement the international ITI study already started: an
      observational study in patients who had already experienced a failure with a VWF
      free FVIII concentrate, called RESIST(exp) (experienced); a randomized,
      controlled study in patients who have never tried an ITI treatment before and at
      high risk to fail, called RESIST(naive) (naive).

PMID- 18078405
TI  - Psoriasis and the eye: prevalence of eye disease in Singaporean Asian patients
      with psoriasis.
AB  - There is little published data on the incidence of eye disease in Asian patients
      with psoriasis. We determined the frequency of ocular complications in
      Singaporean Asian patients with chronic plaque psoriasis and related these to
      extent and severity of psoriasis, family history, treatment and presence of
      arthritis. A cross-sectional prevalence investigation was carried out in 100
      patients who received a comprehensive eye examination. Psoriasis extent and
      severity was graded by the Lattice System Physician's Global Assessment (LS-PGA).
      Two patients (four eyes) had uveitis, one of whom had psoriatic arthritis (2%
      incidence). Presence or absence of uveitis correlated with mean LS-PGA scores.
      Sixty-three patients had cataract unrelated to previous steroid or phototherapy
      treatment; in younger (<50 years) patients they were commoner than in those with
      higher (>5) LS-PGA scores. Three eyes in two patients (2% prevalence) had
      glaucomatous optic neuropathy unrelated to previous treatment, and comparable
      with expected population frequency. These findings, although limited by lack of
      data from a comparable control population, suggest that eye complications are
      common in Asian patients with psoriasis and eye symptoms should be elicited
      during history taking. Besides signs and symptoms of eye disease, an LS-PGA score
      of more than 5 should prompt referral for ophthalmological examination.

PMID- 18078406
TI  - Clinical effects of undershirts coated with borage oil on children with atopic
      dermatitis: a double-blind, placebo-controlled clinical trial.
AB  - It has been reported that gamma-linolenic acid contained in borage oil is
      effective against atopic dermatitis. The clinical effects of undershirts coated
      with borage oil rich in gamma-linolenic acid on atopic dermatitis were evaluated.
      Thirty-two children, aged 1-10 years, were involved in the clinical control
      study. Sixteen had worn undershirts coated with borage oil everyday for 2 weeks,
      and 16 had worn non-coated undershirts as a placebo. Their symptoms were assessed
      on a 4-point scale. Those children who had worn undershirts coated with borage
      oil for 2 weeks showed improvements in their erythema and itch, which were
      statistically significant. Transepidermal water loss from the back was decreased.
      In the placebo group, there were no statistically significant differences. The
      undershirts coated with borage oil were found to be statistically effective, and
      had no side-effects on children with mild atopic dermatitis.

PMID- 18078407
TI  - Successful treatment of disseminated superficial actinic porokeratosis with Q
      switched ruby laser.
AB  - Porokeratosis, a cutaneous disorder that is characterized histologically by the
      presence of a "cornoid lamella", is a progressive disease with limited
      therapeutic modalities. We report a case of a 61-year-old man suffering from
      disseminated superficial actinic porokeratosis, one of the clinical types of
      porokeratosis, treated with Q-switched ruby laser, commonly used for the
      treatment of pigmented skin diseases. The laser therapy provided striking
      improvement and no clinical recurrence was noted.

PMID- 18078408
TI  - Nodular malignant melanoma with Spitz nevus-like pathological features finally
      confirmed by the pathological feature of the sentinel lymph node.
AB  - The clinical and histopathological similarities of nodular melanoma and Spitz
      nevus currently still make a definitive diagnosis difficult. We report here a
      case of nodular melanoma that was extremely difficult to diagnose both clinically
      and histopathologically. The primary tumor was a blackish nodule on the scalp and
      biopsy was performed for pathological diagnosis. Although our first impression
      was malignant melanoma, we asked two dermatopathologists for second opinions;
      however, one diagnosed a melanoma and the other a Spitz nevus. Faced with this
      clinical dilemma, an operation was performed with sentinel node biopsy. Only one
      sentinel node suggested a metastasis. Histopathological diagnosis to establish
      whether it was a melanoma metastasis or nodal nevi was also difficult, and we
      again asked for second opinions from another dermatopathologist in the USA.
      According to its clinical course and the histopathology of the sentinel lymph
      node with additional immunohistochemistry, this case was finally diagnosed as a
      nodular melanoma (T4aN1aM0, stage IIIA). To date, the patient has been given five
      courses of chemotherapy at 6-month intervals, with no local recurrence or distant
      metastases so far.

PMID- 18078409
TI  - Recurrent sarcoidosis on a scar associated with vitiligo.
AB  - We report a case of systemic sarcoidosis, diagnosed 13 years ago by
      transbronchial biopsy. Our patient had a spontaneous resolution of hilar and
      mediastinal lymphadenopathy 6 months after diagnosis. She presented with a skin
      rash on her thyroidectomy scar after a period of 4 years of complete remission.
      The patient complained that her thyroidectomy incision scar rose up, reddened and
      hardened. Biopsy of the skin lesion revealed non-caseating epithelioid granulomas
      with histiocytes and multinucleated giant cells. She was successfully treated
      with oral prednisone. Scar sarcoidosis recurred twice in a 7-year follow-up
      period without accompanying systemic sarcoidosis. Vitiligo appeared with the last
      relapse of scar sarcoidosis. The case we present is of interest due to the
      recurrent attacks of scar sarcoidosis in a patient during the remission period of
      systemic sarcoidosis. Another aspect of this case is the association of the
      disease with vitiligo without any sign of an autoimmune disease.

PMID- 18078410
TI  - Sanitary napkin contact dermatitis of the vulva: location-dependent differences
      in skin surface conditions may play a role in negative patch test results.
AB  - I herein report six Japanese female patients with sanitary napkin contact
      dermatitis of the vulva. This condition may not be uncommon, although only a few
      reports have been published in Europe and the USA and none from Asia. Routine
      patch test with a saline-soaked fragment of their sanitary napkins conducted on
      the flexor surface of the upper arm gave negative results in all the patients,
      although pruritic dermatitis was clinically reproducible, developing in a delayed
      fashion, 2-4 days after the use of any brands of sanitary napkin. Moreover, this
      dermatitis could be avoided by using a tampon together with wearing cotton
      shorts. These observations suggest that it is a kind of irritant dermatitis that
      is induced by the wet local conditions as well as by friction caused by wearing a
      sanitary napkin rather than that due to sanitary napkin components. Resistance of
      the skin against external irritant stimuli is variable among different body sites
      and the genital skin, which is covered by thin stratum corneum, is thought to
      have low resistance against various external irritating and mechanical stimuli
      induced by wearing a sanitary napkin. Moreover, it is reasonable to presume that
      the proliferation of the resident microorganisms of the genital skin that takes
      place under the wet conditions produced by the use of the napkin also plays a
      role in the induction of such a unique contact dermatitis. Unfortunately, the
      commonly employed patch testing method performed on the skin of the upper limb or
      back cannot simulate the local situation occurring on the vulva under the
      sanitary napkin. We are urgently in need of a modification in patch testing
      method that is suited to reproduce similar dermatitis in other body locations.

PMID- 18078411
TI  - Knuckle pads associated with clubbed fingers.
AB  - The patient was a 37-year-old male who visited us for the chief complaints of
      severely keratinized elastic soft nodules with normal skin color or slightly
      glossy pale brown color at the distal interphalangeal joints of the bilateral
      second, third, fourth and fifth fingers associated with bilateral clubbed
      fingers. The nodules were histopathologically diagnosed as knuckle pads. Clubbed
      fingers were also noted, but no cardiopulmonary disorder was observed. Knuckle
      pads are circumscribed fibromatous thickenings of the skin overlying the finger
      joints. External factors are considered to be the cause, but many cases may be
      idiopathic such as this case. Many patients with clubbed fingers have underlying
      cardiopulmonary disorders, and idiopathic development, such as in this case, does
      not frequently occur. Our patient had the complications of knuckle pads and
      clubbed fingers, which has not previously been reported.

PMID- 18078412
TI  - Nevoid basal cell carcinoma syndrome successfully treated with trichloroacetic
      acid and phenol peeling.

PMID- 18078413
TI  - Basal cell carcinoma with an epidermal collarette.

PMID- 18078414
TI  - Successful treatment of cutaneous Mycobacterium chelonae infection with
      roxithromycin.

PMID- 18078415
TI  - Disseminated lupus vulgaris presenting with different atypical lesions.

PMID- 18078416
TI  - Two cases of alopecia areata responsive to fexofenadine.

PMID- 18078418
TI  - The stress of birth enhances in vitro spontaneous and IL-8-induced neutrophil
      chemotaxis in the human newborn.
AB  - The birth process induces fetal stress. Stress has profound effects on the immune
      system, also by acting on the trafficking of leukocytes, a process in which
      adhesion and chemotaxis are primordial and critical events for the development of
      effective antimicrobial defenses. The newborn is rapidly challenged by a
      microflora at the epithelia linings and therefore depending on early, innate
      immunity onset. The objective of the study was to investigate the immune response
      in cord blood from newborns in relation to different degrees of fetal stress,
      with focus on neutrophil chemotaxis. We analyzed in vitro transmigration ability
      of neutrophils and their CD11b expression, measured total white blood count (WBC)
      and the major leukocyte populations, interleukin (IL)-8, interferon (IFN)-gamma,
      and soluble E-Selectin, as well as relevant immuno-modulating hormones in infants
      born at term after Cesarean section prior to the start of labor (n = 55), normal
      vaginal delivery (n = 87), and assisted delivery (n = 26). Arterial pH and
      lactate were used as stress markers. We found that spontaneous and IL-8-induced
      transmigration ability of neutrophils from newborns after normal delivery was
      significantly higher compared with that of neutrophils from Cesarean section or
      from adults. With a progressive increase in fetal stress, there were significant
      elevations in total WBC, in particular neutrophils and monocytes, as well as an
      enhanced IL-8 and soluble E-Selectin level. Assisted delivery, associated with
      the highest degree of fetal stress in addition had an enhanced lymphocyte and
      monocytes count as well as an increased IFN-gamma level. There were significant
      direct correlations between neutrophils and monocytes, respectively, with
      cortisol, beta-endorphin, and prolactin. Interferon-gamma was directly related to
      dopamine, as well as to the lymphocyte and monocyte count. The setting of the HPA
      axis at birth is a promoter of an alarm response and a surge of neuroendocrine
      immuno-modulating factors that enhances antimicrobial defenses of the newborn. We
      speculate that IL-8 induced by normal labor may be a priming factor for an
      increased neutrophil chemotaxis through the pre-activated endothelium of the
      fetus. Assisted delivery may trigger excessive recruitment of additional
      inflammatory cells and IFN-gamma release.

PMID- 18078419
TI  - Urticaria Neonatorum: accumulation of tryptase-expressing mast cells in the skin
      lesions of newborns with Erythema Toxicum.
AB  - Erythema Toxicum, a rash frequently present in the healthy newborn infant is an
      innate, immune response to the first commensal micro flora. Flushing and
      urtication are seen in this manifestation suggesting mast cell (MC) activation
      and MC derived mediator release. It has recently become evident that MCs
      participate in the protective, innate immune response against microbes also by
      secreting products toxic to pathogens such as cathelicidin peptide antibiotics.
      We hypothesized that MCs contribute to the process of inflammation in Erythema
      Toxicum and that skin MCs of human newborns express the cathelicidin peptide
      antibiotic LL-37. Skin sections were immunostained for MC tryptase. Double
      immunofluorescence was performed by staining LL-37 in combination with tryptase.
      We studied ultra structure of skin MCs with transmission (TEM) and immunoelectron
      microscopy (IEM). Seven infants with and six infants without the rash, as well as
      three adults were included. We found numerous tryptase-expressing MCs recruited
      around the hair follicles in the lesions of Erythema Toxicum. TEM analysis of MCs
      exhibited signs of degranulation in the lesion. Neither skin MCs from newborns
      nor adults did express LL-37 as judged by confocal and IEM. MCs participate in
      the inflammatory responses of Erythema Toxicum by taking an active part in the
      immune system of the hair follicle. However, their immunological activity is not
      linked to the expression of the cathelicidin antimicrobial peptide LL-37. A
      pivotal role of MCs in the innate, inflammatory response at the site of pathogen
      invasion during the critical time of perinatal colonization is suggested.

PMID- 18078420
TI  - CD30 on stimulated CD4+ T lymphocytes in newborns regarding atopic heredity.
AB  - CD30 was initially described as Ki-1 Ag on Reed-Sternberg cells of Hodgkin's
      lymphoma and its and CD30L(+) expression on T cells in placenta were equally
      frequent in the atopic and non-atopic women. In this article we present a study
      of CD30 mean fluorescence intensity (MFI) on CB T CD4(+) cells. We tested the
      hypothesis that in newborns with atopy family history there is a changed CB T
      cells response after antigen stimulation comparing with those without atopy
      family history. The study population consisted of 31 newborn babies (29
      breastfed, two non-breastfed) and their mothers. Eleven of them had positive and
      20 had negative atopy family history. Performed tests included cord blood, which
      was a subject to flowcytometry analysis and was cultured for 24 h, cytokine
      production was measured (IFN- gamma, IL-4 and IL-12). Secondly, we measured total
      maternal and cord blood IgE levels. We studied CD30 MFI as in our studies in
      larger group of newborns, CD30 expression on CD4(+) T cells appeared to be very
      low. MFI of CD4(+) CD30(+) after PHA-stimulation (213.55: range: 41.77-434.51)
      was significantly increased compared to MFI of CD4(+) CD30(+) before PHA
      stimulation (43.63: range 28.67-134.67)(p </= 0.001). Newborns with and without
      atopy family history were analyzed. We found no difference between MFI of CD4(+)
      CD30(+) on non-stimulated T cells in non-atopic (43.80: range 28.66-134.66) and
      atopic (43.30: range 29.12-80.92) (p > 0.05). After PHA stimulation MFI of CD4(+)
      CD30(+) in non-atopic (273.05 (range: 42.9-434.51) was significantly increased
      compared with the atopic newborns to MFI of 87.1 (range: 41.78-241.42) (p =
      0.00). We have not found any correlation between MFI of CD4(+) CD30(+) and total
      maternal and total CB IgE levels. The role of CD30 in immunological response
      needs further research studies.

PMID- 18078421
TI  - The influence of age and gender on sensitization to aero-allergens.
AB  - Boys run a higher risk for atopy than girls but this gender difference is less
      pronounced in adulthood. The underlying mechanisms and the exact timing of this
      decrease in male/female ratio remain unclear. The aim of this study was to
      evaluate the effect of age and gender on sensitization in schoolchildren. A cross
      sectional study was performed in an unbiased community population of 2021 Belgian
      schoolchildren, aged 3.4-14.8 yr. The overall sensitization and the sensitization
      for mites, mixed grass pollens and tree pollens increased significantly with
      increasing age. Male sex was strongly associated with sensitization (OR(adj) 2.0,
      98% CI 1.6-2.4). Male predominance was more obvious in children under the age of
      8 yr. After the age of 8 male predominance persisted, but a significant increase
      in sensitized females occurred. Our data demonstrate a significant increase in
      prevalence of sensitization with age and a significant decrease in male/female
      ratio of sensitization after the age of 8 yr, although a male predominance
      persists. These data are the first published data ever that document this change
      in male/female ratio in sensitization at this age.

PMID- 18078422
TI  - Neuroendocrine and circadian aspects (melatonin and beta-endorphin) of atopic
      dermatitis in the child.
AB  - Atopic dermatitis (AD) is a disease of increasing incidence among paediatric
      patients. Among the factors involved in its pathogenesis is the alteration of the
      immune response, and so the objective of this study was to evaluate the
      involvement of certain neuroendocrine factors with immune properties in the
      development of the disease. Fifty-five subjects were selected and divided into
      the following three groups: healthy subjects, those diagnosed with symptomatic AD
      and those with asymptomatic AD. Plasma levels of melatonin and beta-endorphins
      were measured by radioimmunoassay, in serum samples obtained at 9 am and 9 pm,
      with two samples being obtained from each of the patients and controls. In the
      phases of AD outbreaks, there is a reduction in the serum levels of both
      melatonin and beta-endorphin. In the case of melatonin, the difference is
      statistically significant only during the day, although nocturnal levels are
      greater for both hormones. In AD, a central neuroendocrine dysfunction may be a
      primary pathogenic event. Our hypothesis is that the physiological nocturnal peak
      of melatonin due to pineal gland production may mask the decline of melatonin of
      possibly extrapineal (immunological) origin during episodes of dermatitis
      outbreaks. Further studies are required, particularly of neurovegetative and
      hormonal aspects, to better define this process. Such a definition would also be
      of therapeutic interest.

PMID- 18078423
TI  - Latex allergy risk assessment in children and adolescents with type I diabetes
      mellitus.
AB  - An increased frequency of allergic reactions to latex has been reported in
      specific populations with chronic latex exposure. However, relevance of latex
      allergy to children and adolescents with type I diabetes mellitus (DM1) has not
      been studied yet. The aim of the studty is to assess latex allergy risk in
      children and adolescents with DM1. Thirty-nine children with DM1 and 35 controls
      were enrolled. In a case-control study, we applied to all subjects a standard
      questionnaire, and specific Immunoglobulin E (IgE) concentrations for latex,
      common aeroallergens, and food-allergens were measured in serum samples. Latex
      exposure rates by means of medical procedures, operations, and latex glove usage
      were not different between DM1 and controls. Symptoms due to latex exposure were
      not determined in both groups. Three (7.7%) subjects in DM1 tested positive for
      latex-specific antibodies (LSIE), whereas no subject in controls. Diabetics that
      tested positive for latex-specific antibodies had the disease for three, 5 and 8
      years. Nine (23.1%) of diabetics, and two (5.7%) of controls were atopic (p =
      0.04). In our investigation, we found that children and adolescents with DM1 are
      not a risk group for latex allergy, and LSIE in children with DM1 was not
      accompanied by symptoms of latex allergy, or, presumably, increased risk of latex
      anaphylaxis.

PMID- 18078424
TI  - Egg allergy.
AB  - Egg allergy is one of the most common food allergies in infants and young
      children. The great majority is not life-threatening and management involves
      exclusion of egg from the diet and regular review with the expectation that the
      majority of children will outgrow the allergy by school age. Judgment is required
      as to when the dietary elimination of egg is no longer required. This decision
      may be helped by demonstrating loss of sensitivity by skin prick or specific IgE
      testing and in some cases a supervised food challenge. Particular issues in
      management arise with more severe, potentially life-threatening reactions, with
      immunization with vaccines prepared in eggs, with the diagnosis of egg
      hypersensitivity as a cause of delayed exacerbations of eczema which can be non
      IgE mediated, and in deciding whether a child can be allowed to ingest small
      amounts of cooked egg through egg-containing foods while continuing to avoid raw
      egg or larger amounts of whole egg. Cases which illustrate these issues are
      presented.

PMID- 18078425
TI  - Ginsenosides: are any of them candidates for drugs acting on the central nervous
      system?
AB  - The last two decades have shown a marked expansion in the number of publications
      regarding the effects of Panax ginseng. Ginsenosides, which are unique saponins
      isolated from Panax ginseng, are the pharmacologically active ingredients in
      ginseng, responsible for its effects on the central nervous system (CNS) and the
      peripheral nervous system. Recent studies have shown that ginsenosides regulate
      various types of ion channels, such as voltage-dependent and ligand-gated ion
      channels, in neuronal and heterologously expressed cells. Ginsenosides inhibit
      voltage-dependent Ca(2+), K(+), and Na(+) channel activities in a stereospecific
      manner. Ginsenosides also inhibit ligand-gated ion channels such as N-methyl-d
      aspartate, some subtypes of nicotinic acetylcholine, and 5-hydroxytryptamine type
      3 receptors. Competition and site-directed mutagenesis experiments revealed that
      ginsenosides interact with ligand-binding sites or channel pore sites and inhibit
      open states of ion channels. This review will introduce recent findings and
      advances on ginsenoside-induced regulation of ion channel activities in the CNS,
      and will further expand the possibilities that ginsenosides may be useful and
      potentially therapeutic choices in the treatment of neurodegenerative disorders.

PMID- 18078426
TI  - TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo [4,5-g]isoquinoline): discovery,
      pharmacological effects, and therapeutic potential.
AB  - Chemically, TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline) can be
      viewed as a conformationally restricted phenylalkylamine that is related in
      structure to amphetamine but does not stimulate (or depress) locomotor activity
      in rodents. In radioligand binding studies TDIQ displays selective affinity for
      alpha(2)-adrenergic receptor subsites (i.e., alpha(2A)-, alpha(2B)-, and
      alpha(2C)-adrenergic receptors), and behavioral data suggest that it might exert
      an agonist (or partial agonist) effect at alpha(2)-adrenergic receptors or
      interact at alpha(2)-adrenergic heteroreceptors. Drug discrimination studies in
      rats indicate that TDIQ: (1) serves as a discriminative stimulus, (2) may be
      useful in the treatment of symptoms associated with the abuse of cocaine, and (3)
      exhibits a low potential for abuse. In addition, TDIQ exhibits a dose-dependent
      and wide dissociation between doses that produce an anxiolytic-like effect or an
      inhibition of "snack" consumption in mice and doses that produce minimal, if any,
      effects in tests that measure a potential for disruption of coordinated movement
      or motor activity. Also, TDIQ displays negligible effects on the heart rate (HR)
      and blood pressure (BP) of mice. Taken together, the preclinical data suggest
      that TDIQ exhibits a favorable ratio of therapeutic-like effects (anxiolytic,
      therapeutic adjunct in the treatment of cocaine abuse, and appetite suppression)
      to side effect-like activities (behavioral impairment, drug abuse, or adverse
      cardiovascular effect). As such, TDIQ could: (1) be a forerunner for a new type
      of chemical entity in the treatment of certain forms of anxiety and/or obesity
      and (2) serve as a structural template in the discovery and development of
      additional agents that might be selective for alpha(2)-adrenergic receptors.

PMID- 18078427
TI  - Cortagine: behavioral and autonomic function of the selective CRF receptor
      subtype 1 agonist.
AB  - Corticotropin-releasing factor (CRF) is a neuropeptide and mediating component of
      neuroendocrine, autonomic, and behavioral processes associated with the stress
      response. The two receptor subtypes identified in the mammalian brain, CRF
      receptor subtype 1 (CRF1) and CRF2, are suggested to differentially modulate
      these processes. Manipulation of these receptors with selective CRF compounds and
      transgenic models has revealed, in most studies, a clear potentiation of the
      stress response through central activation of CRF1. However, pharmacological
      activation of CRF restricted to CRF1 has been limited by the availability of
      selective peptidic compounds. Recently, a highly selective CRF1 agonist,
      cortagine, has been developed. It was synthesized from chimeric intermediate
      sequences of ovine CRF, sauvagine, and human/rat CRF into a highly soluble
      peptide with strong affinity for CRF1 (IC(50) < 5 nM) and a very low binding
      preference for CRF2 (IC(50) > 500 nM). Affinity for the CRF binding protein
      (IC(50) > 1,000 nM) can be abolished by the addition of a glutamate residue on
      position 21 of the cortagine peptide sequence. Cortagine has recently been tested
      in a variety of preclinical models of behavior including the elevated-plus-maze
      (EPM), forced swim test (FST), homecage, and rat exposure test (RET). Preliminary
      characterization in the EPM and FST suggested that this compound elicits
      anxiogenic and antidepressant-like effects, respectively. Additional testing in
      the homecage and RET, which targets various elements of behavior, directs to a
      more potent anxiogenic profile of cortagine. In this review, we discuss the
      behavioral findings and the tests used to measure these effects. Finally, we also
      discuss preliminary findings of autonomic activation obtained by central
      injection of cortagine that support CRF1 involvement in the modulation of heart
      rate and heart rate variability.

PMID- 18078428
TI  - The preclinical properties of a novel group II metabotropic glutamate receptor
      agonist LY379268.
AB  - Activation of group II metabotropic glutamate (mGlu2/3) receptors reduces
      excessive glutamate release that is often associated with neurodegenerative and
      psychiatric disorders. This finding encouraged the search for potent and
      selective agonists as potential therapeutic agents. The search led to the
      discovery of LY379268 {(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic
      acid}, which is a highly potent and systemically available mGlu2/3 receptor
      agonist. LY379268 was effective in several animal models of stroke, epilepsy,
      drug abuse, schizophrenia, and pain. Suppression of motor activity is the major
      side effect of LY379268. Upon repeated administration tolerance develops to this
      side effect, while the therapeutic effects of LY379268 remain. To date, no
      clinical data with LY379268 are available. This review article summarizes the
      preclinical pharmacology of LY379268.

PMID- 18078429
TI  - Guanfacine and guanfacine extended release: treatment for ADHD and related
      disorders.
AB  - Guanfacine, an alpha(2A) adrenoceptor agonist, is U.S. Food and Drug
      Administration (FDA)-approved for the treatment of hypertension in adolescents
      and adults. It also has been used "off-label" for several years in children as a
      possible treatment for attention-deficit/hyperactivity disorder (ADHD) and
      pervasive developmental disorders (PDDs). Small placebo-controlled trials support
      the use of guanfacine for the treatment of ADHD. There is more limited research
      on the use of guanfacine in treating hyperactivity occurring in children
      diagnosed with PDD. Recently, guanfacine extended release (GXR), a once-daily
      formulation has been manufactured and studied in phase III clinical trials. Based
      on preliminary scientific presentations, it also appears to be efficacious in
      improving ADHD in children. The most common adverse effects associated with
      guanfacine and GXR treatment is sedation. Adverse cardiovascular effects are
      uncommon, although modest reductions in blood pressure and heart rate are common.
      If GXR is FDA-approved, it would be the first alpha(2A) adrenoceptor agonist
      marketed for ADHD.

PMID- 18078430
TI  - Pharmacology of the beta-carboline FG-7,142, a partial inverse agonist at the
      benzodiazepine allosteric site of the GABA A receptor: neurochemical,
      neurophysiological, and behavioral effects.
AB  - Given the well-established role of benzodiazepines in treating anxiety disorders,
      beta-carbolines, spanning a spectrum from full agonists to full inverse agonists
      at the benzodiazepine allosteric site for the GABA(A) receptor, can provide
      valuable insight into the neural mechanisms underlying anxiety-related physiology
      and behavior. FG-7,142 is a partial inverse agonist at the benzodiazepine
      allosteric site with its highest affinity for the alpha1 subunit-containing
      GABA(A) receptor, although it is not selective. FG-7,142 also has its highest
      efficacy for modulation of GABA-induced chloride flux mediated at the alpha1
      subunit-containing GABA(A) receptor. FG-7,142 activates a recognized anxiety
      related neural network and interacts with serotonergic, dopaminergic,
      cholinergic, and noradrenergic modulatory systems within that network. FG-7,142
      has been shown to induce anxiety-related behavioral and physiological responses
      in a variety of experimental paradigms across numerous mammalian and non
      mammalian species, including humans. FG-7,142 has proconflict actions across
      anxiety-related behavioral paradigms, modulates attentional processes, and
      increases cardioacceleratory sympathetic reactivity and neuroendocrine
      reactivity. Both acute and chronic FG-7,142 treatment are proconvulsive,
      upregulate cortical adrenoreceptors, decrease subsequent actions of GABA and beta
      carboline agonists, and increase the effectiveness of subsequent GABA(A) receptor
      antagonists and beta-carboline inverse agonists. FG-7,142, as a partial inverse
      agonist, can help to elucidate individual components of full agonism of
      benzodiazepine binding sites and may serve to identify the specific GABA(A)
      receptor subtypes involved in specific behavioral and physiological responses.

PMID- 18078431
TI  - A review of clinical trials with eptifibatide in cardiology.
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. Additional antithrombin therapy should be given in connection
      with GP IIb/IIIa administration. Eptifibatide is a small heptapeptide, which is
      highly selective and rapidly dissociates from its receptor after cessation of
      therapy. In clinical trials (IMPACT-II and ESPRIT) concomitant administration of
      eptifibatide to patients undergoing percutaneous coronary intervention (PCI)
      reduced thrombotic complications. In the PURSUIT trial, in patients with non-ST
      elevation acute coronary syndromes, eptifibatide, compared to placebo,
      significantly reduced the primary endpoint of death and nonfatal myocardial
      infarction at 30 days. In patients with STEMI eptifibatide has been studied as an
      adjunct to fibrinolysis and primary PCI; it improved epicardial flow and tissue
      reperfusion. Current studies are evaluating eptifibatide as upstream therapy in
      high-risk patients with NSTE-ACS, in the EARLY-ACS and in comparison with
      abciximab in patients with primary PCI in the EVA-AMI trial.

PMID- 18078432
TI  - Clinical use of sirolimus-eluting stents.
AB  - Drug-eluting stents, or intracoronary stents that combine the local delivery of
      antirestenotic pharmacologic therapies while maintaining the mechanical advantage
      of bare metal stents over balloon angioplasty alone, are a highly complex
      technology that have profoundly affected the practice of percutaneous coronary
      intervention over the last 5 years. These devices were designed specifically to
      treat the neointimal hyperplasia occurring after conventional bare metal stent
      placement, and have been remarkably successful in this regard. However, recent
      concerns have been raised regarding the long-term safety of these devices,
      particularly when used outside of the specific patient and lesion subsets studied
      in the pivotal randomized trials that led to device approval by regulatory bodies
      within the United States and abroad. This review aims to present a brief
      description of the sirolimus-eluting stent device platform and its mechanism of
      action, followed by an overview of current data regarding efficacy and safety
      regarding the clinical use of sirolimus-eluting stent technology.

PMID- 18078433
TI  - Serofendic acid, a substance extracted from fetal calf serum, as a novel drug for
      cardioprotection.
AB  - We previously identified a novel endogenous substance, serofendic acid, from a
      lipophilic extract of fetal calf serum. The compound, a low-molecular-weight
      sulfur-containing atisane-type diterpenoid, exhibited potent protective action
      against neurotoxicity induced by glutamate, nitric oxide, and oxidant stress. We
      investigated whether this substance has a cardioprotective effect. Primary
      cultures of neonatal rat cardiac myocytes were exposed to oxidant stress (H2O2)
      to induce cell death. Pretreatment with serofendic acid significantly suppressed
      cell death induced by H2O2, and the cytoprotective effect was closely associated
      with the preservation of mitochondrial function. Serofendic acid inhibited H2O2
      induced loss of mitochondrial membrane potential in a concentration-dependent
      manner (with saturation by 100 microM), by attenuating matrix calcium overload
      and intracellular accumulation of reactive oxygen species. The protective effect
      of serofendic acid was comparable to that of a mitochondrial ATP-sensitive
      potassium (mitoK ATP) channel opener, diazoxide. Furthermore, mitoK ATP channel
      blocker, 5-hydroxydecanoate, abolished the protective effect of serofendic acid.
      Serofendic acid and diazoxide, administered together, at 100 microM each, had no
      additive effects. Thus, serofendic acid inhibited the oxidant-induced
      mitochondrial death pathway, presumably through activation of the mitoK(ATP)
      channel. In conclusion, serofendic acid appears to protect cardiac myocytes from
      oxidant-induced cell death by preserving the functional integrity of
      mitochondria. Our findings suggest that serofendic acid may represent a novel
      candidate for cardioprotective therapy in ischemia/reperfusion injury.

PMID- 18078434
TI  - A multiple ion channel blocker, NIP-142, for the treatment of atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is one of the most frequent cardiac arrhythmia and is
      associated with increased cardiovascular morbidity and mortality, and the risk of
      stroke. Although currently available antiarrhythmic drugs are moderately
      effective in restoring normal sinus rhythm in patients with AF, excessive delay
      of ventricular repolarization by these agents may be associated with increased
      risk of proarrhythmia. Therefore, selective blockers of cardiac ion channel(s)
      that are exclusively present in the atria are highly desirable. NIP-142 is a
      novel benzopyrane derivative, which blocks potassium, calcium, and sodium
      channels and shows atrial specific action potential duration prolongation. NIP
      142 preferentially blocks the ultrarapid delayed rectifier potassium current (I
      Kur) and the acetylcholine-activated potassium current (I KACh). Since I Kur and
      I KACh have been shown to be expressed more abundantly in the atrial than in the
      ventricular myocardium, the atrial-specific repolarization prolonging effect of
      NIP-142 is considered to be due to the blockade of these potassium currents. In
      canine models, NIP-142 was shown to terminate the microreentry type AF induced by
      vagal nerve stimulation and the macroreentry type atrial flutter induced by an
      intercaval crush. These effects of NIP-142 have been attributed to the
      prolongation of atrial effective refractory period (ERP), because this compound
      prolonged atrial ERP without affecting intraatrial and interatrial conduction
      times in these models. The ERP prolongation by NIP-142 was greater in the atrium
      than in the ventricle. NIP-142 also terminated the focal activity type AF induced
      by aconitine. In addition, NIP-142 reversed the atrial ERP shortening and the
      loss of rate adaptation induced by short-term rapid atrial pacing in anesthetized
      dogs. Thus, although clinical trials are required to provide evidence for its
      efficacy and safety, the novel multiple ion channel blocker, NIP-142, appears to
      be a useful agent for the treatment of several types of AF with a low risk of
      proarrhythmic activity.

PMID- 18078435
TI  - Prasugrel: a novel thienopyridine antiplatelet agent. A review of preclinical and
      clinical studies and the mechanistic basis for its distinct antiplatelet profile.
AB  - Prasugrel (CS-747, LY640315) is a novel member of the thienopyridine class of
      oral antiplatelet agents that includes ticlopidine and clopidogrel. Like other
      thienopyridines, prasugrel is a prodrug that is inactive in vitro. Prasugrel's
      distinct chemical structure permits efficient conversion to its active metabolite
      with a less rigorous dependence on specific cytochrome P-450 enzymes. Prasugrel
      is rapidly converted in vivo to an active metabolite (R-138727) that binds
      specifically and irreversibly to the platelet P2Y 12 purinergic receptor
      inhibiting ADP-mediated platelet activation and aggregation. Preclinical studies
      indicated that prasugrel is approximately 10- and 100-fold more potent at
      inhibiting ex vivo platelet aggregation and in vivo thrombus formation than
      clopidogrel and ticlopidine, respectively. Early clinical data in healthy
      subjects confirmed the greater platelet inhibition and consistency with prasugrel
      compared to clopidogrel. While the active metabolites of prasugrel and
      clopidogrel resulted in similar levels of platelet inhibition in vitro, the
      amount of each active metabolite generated in vivo was quite different-prasugrel
      (60 mg) resulting in an approximately 12-fold greater exposure to its active
      metabolite compared with clopidogrel (300 mg). This observation provides a
      mechanistic basis for the faster, greater, and more consistent inhibition of
      platelet aggregation observed with prasugrel. Clinical studies in patients with
      cardiovascular disease confirmed the potent antiplatelet effect of prasugrel
      compared with clopidogrel. Collectively, these phase 1/1b studies and a phase 2
      study (JUMBO-TIMI 26) aided in dose selection for the recently completed phase 3
      trial (TRITON-TIMI 38) in patients with acute coronary syndrome undergoing
      percutaneous coronary intervention.

PMID- 18078436
TI  - Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular
      benefits.
AB  - Oleogum resin (known as guggul) from the guggul tree, Commiphora mukul, found in
      India, Bangladesh, and Pakistan, has been used to treat various diseases
      including hyper-cholesterolemia, atherosclerosis, rheumatism, and obesity over
      several thousands of years. Guggulsterone isolated from guggul has been
      identified as the bioactive constituent responsible for guggul's therapeutic
      effects. Since the first study demonstrating the therapeutic effects of guggul in
      an animal model in 1966, numerous preclinical and clinical trails have been
      carried out. Although differences in study design, methodological quality,
      statistical analysis, sample size, and subject population result in certain
      inconsistencies in the response to therapy, the cumulative data from in vitro,
      preclinical, and clinical studies largely support the therapeutic claims for
      guggul described in the ancient Ayurvedic text. However, future clinical studies
      with much larger size and longer term are required to confirm these claims. The
      cardiovascular benefits of the therapy are derived from the multiple
      pharmacological activities associated with guggul or guggulsterone, notably its
      hypolipidemic, antioxidant, and antiinflammatory activities. It has been
      established that guggulsterone is an antagonist at farnesoid x receptor (FXR), a
      key transcriptional regulator for the maintenance of cholesterol and bile acid
      homeostasis. The FXR antagonism by guggulsterone has been proposed as a mechanism
      for its hypolipidemic effect. A recent study demonstrates that guggulsterone
      upregulates the bile salt export pump (BSEP), an efflux transporter responsible
      for removal of cholesterol metabolites, bile acids from the liver. Such
      upregulation of BSEP expression by guggulsterone favors cholesterol metabolism
      into bile acids, and thus represents another possible mechanism for its
      hypolipidemic activity. Guggulsterone has been found to potently inhibit the
      activation of nuclear factor-kappaB (NF-kappaB), a critical regulator of
      inflammatory responses. Such repression of NF-kappaB activation by guggulsterone
      has been proposed as a mechanism of the antiinflammatory effect of guggulsterone.

PMID- 18078439
TI  - Beta toxin is essential for the intestinal virulence of Clostridium perfringens
      type C disease isolate CN3685 in a rabbit ileal loop model.
AB  - Clostridium perfringens type C isolates, which cause enteritis necroticans in
      humans and enteritis and enterotoxaemias of domestic animals, typically produce
      (at minimum) beta toxin (CPB), alpha toxin (CPA) and perfringolysin O (PFO)
      during log-phase growth. To assist development of improved vaccines and
      therapeutics, we evaluated the contribution of these three toxins to the
      intestinal virulence of type C disease isolate CN3685. Similar to natural type C
      infection, log-phase vegetative cultures of wild-type CN3685 caused haemorrhagic
      necrotizing enteritis in rabbit ileal loops. When isogenic toxin null mutants
      were prepared using TargeTron technology, even a double cpa/pfoA null mutant of
      CN3685 remained virulent in ileal loops. However, two independent cpb null
      mutants were completely attenuated for virulence in this animal model.
      Complementation of a cpb mutant restored its CPB production and intestinal
      virulence. Additionally, pre-incubation of wild-type CN3685 with a CPB
      neutralizing monoclonal antibody rendered the strain avirulent for causing
      intestinal pathology. Finally, highly purified CPB reproduced the intestinal
      damage of wild-type CN3685 and that damage was prevented by pre-incubating
      purified CPB with a CPB monoclonal antibody. These results indicate that CPB is
      both required and sufficient for CN3685-induced enteric pathology, supporting a
      key role for this toxin in type C intestinal pathogenesis.

PMID- 18078440
TI  - Farnesol and dodecanol effects on the Candida albicans Ras1-cAMP signalling
      pathway and the regulation of morphogenesis.
AB  - Candida albicans hypha formation which has been stimulated via the Ras1-cAMP-Efg1
      signalling cascade is inhibited by farnesol, a C. albicans autoregulatory factor,
      and small molecules such as dodecanol. In cultures containing farnesol or
      dodecanol, hypha formation was restored upon addition of dibutyryl-cAMP. The CAI4
      Ras1(G13V) strain, which carries a dominant-active variant of Ras1 and forms
      hyphae in the absence of inducing stimuli, grew as yeast in medium with farnesol
      or dodecanol; the heat shock sensitivity of the CAI4-Ras1(G13V) strain was also
      suppressed by these compounds. Neither Pde1 nor Pde2 was necessary for the
      repression of hyphal growth by farnesol or dodecanol. Two transcripts, CTA1 and
      HSP12, which are at higher levels upon mutation of Ras1 or Cdc35, were increased
      in abundance in cells grown with farnesol or dodecanol. Microscopic analysis of
      strains carrying CTA1 and HWP1 promoter fusions grown with intermediate
      concentrations of farnesol or dodecanol indicated a link between cells with the
      increased expression of cAMP-repressed genes and cells repressed for hypha
      formation. Because several cAMP-controlled outputs are affected by farnesol and
      dodecanol, our findings suggest that these compounds impact activity of the Ras1
      Cdc35 pathway, thus leading to an alteration of C. albicans morphology.

PMID- 18078441
TI  - Sensing of 5' monophosphate by Escherichia coli RNase G can significantly enhance
      association with RNA and stimulate the decay of functional mRNA transcripts in
      vivo.
AB  - The RNase E/G family of endoribonucleases has a central role in RNA degradation
      and processing. Previous work has shown that their cleavage of substrates in
      vitro can be stimulated by the presence of a 5' monophosphate group. It has not
      however, established the importance of this activation for any natural RNA
      processing or decay pathway in vivo. Here we provide for Escherichia coli RNase G
      the first evidence that the sensing of a 5' monophosphate is required in vivo for
      the normal rapid decay of functional mRNAs; moreover, we show in vitro that, in
      contrast to a previous study, the presence of a 5' monophosphate can enhance the
      affinity of RNase G binding to RNA. The implications of these results along with
      our finding that the maturation of 16S rRNA is unaffected in cells containing an
      RNase G mutant impaired in 5' end sensing are discussed with regard to current
      models of RNA processing and decay and the molecular mechanism that underlies RNA
      cleavage by the RNase E/G family.

PMID- 18078442
TI  - Experimental analysis of Helicobacter pylori transcriptional terminators suggests
      this microbe uses both intrinsic and factor-dependent termination.
AB  - In this study, we report experimental analysis of transcriptional terminators in
      the human pathogen Helicobacter pylori. Previous bioinformatics approaches came
      to differing conclusions regarding transcriptional termination in this bacterium.
      We used a reporter construct, the tnpR-encoded resolvase, to assess terminators.
      In our first experiments, we found that a subset of previously predicted
      intrinsic terminators for H. pylori are functional. In our second experiments, we
      used an unbiased screen to identify putative terminators and then characterized
      18 of these. We found that these putative terminators overlap genomic regions
      that are either intergenic or intragenic. Using reverse transcription PCR, we
      showed that an intergenic terminator and an intragenic antisense terminator
      function at their endogenous loci. Additionally, we found that putative
      terminators contain features of both intrinsic and Rho-dependent termination, but
      that intrinsic terminators define the majority. We were unable to delete rho,
      however, in H. pylori, suggesting that it is essential and likely important.
      Finally, we carried out a mutational analysis of one of our randomly identified
      terminators that has both intrinsic and Rho-dependent features, and found that
      they are both functional. In conclusion, we found that H. pylori possesses
      numerous Rho-dependent and intrinsic terminators including some found in
      intragenic regions.

PMID- 18078443
TI  - Melatonin and the hair follicle.
AB  - Melatonin, the chief secretory product of the pineal gland, has long been known
      to modulate hair growth, pigmentation and/or molting in many species, presumably
      as a key neuroendocrine regulator that couples coat phenotype and function to
      photoperiod-dependent environmental and reproductive changes. However, the
      detailed effects and mechanisms of this surprisingly pleiotropic indole on the
      hair follicle (HF) regarding growth control and pigmentation have not yet been
      completely understood. While unspecific melatonin binding sites have long been
      identified (e.g., in goat and mouse HFs), specific melatonin membrane MT2
      receptor transcripts and both protein and mRNA expression for a specific nuclear
      melatonin binding site [retinoid-related orphan receptor alpha (RORalpha)] have
      only recently been identified in murine HFs. MT1, known to be expressed in human
      skin cells, is not transcribed in mouse skin. After initial enzymologic data from
      hamster skin related to potential intracutaneous melatonin synthesis, it has
      recently been demonstrated that murine and human skin, namely human scalp HFs in
      anagen, are important sites of extrapineal melatonin synthesis. Moreover, HF
      melatonin production is enhanced by catecholamines (as it classically occurs in
      the pineal gland). Melatonin may also functionally play a role in hair-cycle
      control, as it down-regulates both apoptosis and estrogen receptor-alpha
      expression, and modulates MT2 and RORalpha expression in murine skin in a hair
      cycle-dependent manner. Because of melatonin's additional potency as a free
      radical scavenger and DNA repair inducer, the metabolically and proliferatively
      highly active anagen hair bulb may also exploit melatonin synthesis in loco as a
      self-cytoprotective strategy.

PMID- 18078444
TI  - Cardiovascular diseases: protective effects of melatonin.
AB  - This brief review considers some of the cardiac diseases and conditions where
      free radicals and related reactants are believed to be causative. The report also
      describes the beneficial actions of melatonin against oxidative cardiovascular
      disorders. Based on the data available, melatonin seems to have cardioprotective
      properties via its direct free radical scavenger and its indirect antioxidant
      activity. Melatonin efficiently interacts with various reactive oxygen and
      reactive nitrogen species (receptor independent actions) and it also upregulates
      antioxidant enzymes and downregulates pro-oxidant enzymes (receptor-dependent
      actions). Moreover, melatonin enters all cells and subcellular compartments and
      crosses morphophysiologic barriers. These findings have implications for the
      protective effects of melatonin against cardiac diseases induced by oxidative
      stress. Melatonin attenuates molecular and cellular damages resulting from
      cardiac ischemia/reperfusion in which destructive free radicals are involved.
      Anti-inflammatory and antioxidative properties of melatonin are also involved in
      the protection against a chronic vascular disease, atherosclerosis. The
      administration of melatonin, as a result of its antioxidant features, has been
      reported to reduce hypertension and cardiotoxicity induced by clinically used
      drugs. The results described herein help to clarify the beneficial effects of
      melatonin against these conditions and define the potential clinical
      applicability of melatonin in cardiovascular diseases.

PMID- 18078445
TI  - Melatonin, endocrine pancreas and diabetes.
AB  - Melatonin influences insulin secretion both in vivo and in vitro. (i) The effects
      are MT(1)-and MT(2)-receptor-mediated. (ii) They are specific, high-affinity,
      pertussis-toxin-sensitive, G(i)-protein-coupled, leading to inhibition of the
      cAMP-pathway and decrease of insulin release. [Correction added after online
      publication 4 December 2007: in the preceding sentence, 'increase of insulin
      release' was changed to 'decrease of insulin release'.] Furthermore, melatonin
      inhibits the cGMP-pathway, possibly mediated by MT(2) receptors. In this way,
      melatonin likely inhibits insulin release. A third system, the IP(3)-pathway, is
      mediated by G(q)-proteins, phospholipase C and IP(3), which mobilize Ca(2+) from
      intracellular stores, with a resultant increase in insulin. (iii) Insulin
      secretion in vivo, as well as from isolated islets, exhibits a circadian rhythm.
      This rhythm, which is apparently generated within the islets, is influenced by
      melatonin, which induces a phase shift in insulin secretion. (iv) Observation of
      the circadian expression of clock genes in the pancreas could possibly be an
      indication of the generation of circadian rhythms in the pancreatic islets
      themselves. (v) Melatonin influences diabetes and associated metabolic
      disturbances. The diabetogens, alloxan and streptozotocin, lead to selective
      destruction of beta-cells through their accumulation in these cells, where they
      induce the generation of ROS. Beta-cells are very susceptible to oxidative stress
      because they possess only low-antioxidative capacity. Results suggest that
      melatonin in pharmacological doses provides protection against ROS. (vi) Finally,
      melatonin levels in plasma, as well as the arylalkylamine-N-acetyltransferase
      (AANAT) activity, are lower in diabetic than in nondiabetic rats and humans. In
      contrast, in the pineal gland, the AANAT mRNA is increased and the insulin
      receptor mRNA is decreased, which indicates a close interrelationship between
      insulin and melatonin.

PMID- 18078446
TI  - Epigenetic regulation: a new research area for melatonin?
AB  - Epigenetic, modifications of DNA and histones, i.e. heritable alterations in gene
      expression that do not involve changes in DNA sequences, are known to be involved
      in disease. Two important epigenetic changes that contribute to disease are
      abnormal methylation patterns of DNA and modifications of histones in chromatin.
      Epimutations, such as the hypermethylation and epigenetic silencing of tumor
      suppressor genes, have revealed a new area for cancer treatment. Studies using
      DNA methyltransferase inhibitors such as procaine, hydralazine, and RG108 have
      had promising outcomes against cancer therapy. Melatonin, one of the most
      versatile molecules in nature, may hypothetically be involved in epigenetic
      regulation. In this review, the potential role of melatonin in inhibiting DNA
      methyltransferase and epigenetic regulation is discussed.

PMID- 18078447
TI  - Melatonin reverses lipopolysaccharide-induced gastro-intestinal motility
      disturbances through the inhibition of oxidative stress.
AB  - A growing number of reports demonstrate that a pro-inflammatory and oxidative
      condition is related to the pathogenesis and the progression of endotoxin-induced
      septic shock and that antioxidants may have therapeutic potential in
      lipopolysaccharide (LPS)-induced sepsis. Melatonin has been shown to possess
      potent antioxidant properties in several models of inflammation in mice and rats.
      In the present study we focused on the possible protective mechanism of melatonin
      in preventing gastrointestinal (GI) disturbances induced by LPS in mice. In fact,
      mice treated with LPS showed a reduced gastric emptying of solid beads. Also the
      geometric center, representing the relative distribution of the solid beads
      throughout the entire GI tract, was significantly reduced in LPS-treated mice
      confirming that sepsis leads to a disturbed GI motility in mice. Melatonin
      completely reversed the LPS-induced motility disturbance. This beneficial effect
      of melatonin is associated with a reduction in lipid peroxidation, MAPK
      activation, NF-kappaB activation, iNOS transcription and expression and nitrite
      production in intestinal tissue from septic mice. These results demonstrate that
      melatonin prevents the LPS-induced GI disturbances in mice switching off the pro
      oxidant pathways induced by the endotoxin. Therefore, it is reasonable to propose
      melatonin as a molecule with therapeutic potential for the treatment of systemic
      inflammation by interfering at the earliest steps of activation of the oxidative
      and pro-inflammatory cascade.

PMID- 18078448
TI  - Melatonin-insulin interactions in patients with metabolic syndrome.
AB  - Metabolic syndrome (MS) as a group of risk factors is strongly associated with
      diabetes type 2 and cardiovascular disease. Insulin resistance plays a key role
      in the pathogenesis of MS. Recent studies have shown that melatonin may influence
      insulin secretion and glucose homeostasis. Therefore, the present study analyzed
      the relationships between the melatonin and the insulin in patients with MS and
      controls. The melatonin rhythm, insulin and lipid levels were studied in 40
      subjects (21 patients and 19 controls) in reproductive age. The night melatonin
      insulin ratio was correlated negatively with low-density lipoprotein cholesterol
      (r = -0.370, p = 0.024) and total cholesterol (r = -0.348, p = 0.030), and
      positively with high-density lipoprotein cholesterol levels (r = +0.414, p =
      0.010). Night-time melatonin levels were related to night-time insulin
      concentrations (r = +0.313, p = 0.049). The correlation was pronounced in
      patients with MS (r = +0.640, p = 0.002), but did not reach statistical
      significance in controls (P > 0.05). In the patients with MS unlike the controls
      the night-day melatonin difference (%) correlated negatively with the fasting
      glucose (r = -0.494, p = 0.023) and positively to daily insulin (r = +0.536, p =
      0.012). Our results show that melatonin-insulin interactions may exist in
      patients with MS, as well as relationships between melatonin-insulin ratio and
      the lipid profile. Pineal disturbances could influence the pathogenesis and the
      phenotype variations of the MS. Larger studies are needed to confirm or reject
      this hypothesis and to clarify the role of the melatonin in the metabolic
      disturbances.

PMID- 18078449
TI  - A randomized, placebo-controlled trial of controlled release melatonin treatment
      of delayed sleep phase syndrome and impaired sleep maintenance in children with
      neurodevelopmental disabilities.
AB  - The purpose of this study was to determine the efficacy of controlled-release
      (CR) melatonin in the treatment of delayed sleep phase syndrome and impaired
      sleep maintenance of children with neurodevelopmental disabilities including
      autistic spectrum disorders. A randomized double-blind, placebo-controlled
      crossover trial of CR melatonin (5 mg) followed by a 3-month open-label study was
      conducted during which the dose was gradually increased until the therapy showed
      optimal beneficial effects. Sleep characteristics were measured by caregiver who
      completed somnologs and wrist actigraphs. Clinician rating of severity of the
      sleep disorder and improvement from baseline, along with caregiver ratings of
      global functioning and family stress were also obtained. Fifty-one children (age
      range 2-18 years) who did not respond to sleep hygiene intervention were
      enrolled. Fifty patients completed the crossover trial and 47 completed the open
      label phase. Recordings of total night-time sleep and sleep latency showed
      significant improvement of approximately 30 min. Similarly, significant
      improvement was observed in clinician and parent ratings. There was additional
      improvement in the open-label somnolog measures of sleep efficiency and the
      longest sleep episode in the open-label phase. Overall, the therapy improved the
      sleep of 47 children and was effective in reducing family stress. Children with
      neurodevelopmental disabilities, who had treatment resistant chronic delayed
      sleep phase syndrome and impaired sleep maintenance, showed improvement in
      melatonin therapy.

PMID- 18078450
TI  - Light/dark patterns of soluble vascular cell adhesion molecule-1 in relation to
      melatonin in patients with ST-segment elevation myocardial infarction.
AB  - Elevated levels of soluble cellular adhesion molecules have been reported in
      patients with acute coronary syndromes. Likewise, a relation between decreased
      nocturnal melatonin levels and coronary artery disease has been suggested. The
      aim of the present study was to investigate the day-night variations in the
      concentration of soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients
      with ST-segment elevation myocardial infarction (STEMI) in relation to the
      light/dark melatonin pattern. Ninety consecutive patients with STEMI who were
      admitted to the Coronary Care Unit of our institution were studied. We also
      recruited 70 age- and gender-matched healthy normal subjects. Blood samples were
      drawn at 09:00 and 02:00 hr, while patients were at rest, for the assessment of
      sVCAM-1 and melatonin, which were measured using commercially available ELISA. In
      STEMI patients, melatonin concentrations maintained a diurnal variation, but the
      difference between nocturnal and diurnal levels was less than that in healthy
      subjects (P < 0.0001). In contrast to findings with melatonin, sVCAM-1 levels
      showed no diurnal variations in control subjects. In the STEMI group, however,
      sVCAM-1 concentration at 02:00 hr was significantly higher than that during the
      light phase (09:00 hr; 1391 +/- 38 versus 1200 +/- 43 ng/mL, P < 0.05). The
      results suggest that diurnal variations in endogenous sVCAM-1 production in STEMI
      patients might be related to an attenuated circadian secretion of melatonin.

PMID- 18078451
TI  - Melatonin inhibits nicotinic currents in cultured rat cerebellar granule neurons.
AB  - There is limited data regarding the effects of melatonin on the activity of
      neuronal acetylcholine receptors (nAChRs) themselves. This study analyzes the
      effects of low concentrations of melatonin on nicotine-evoked currents from
      cerebellar granule neurons (CGNs) in culture. Using electrophysiological and
      Ca(2+)-imaging techniques, it was found a subset of rat CGNs to which nicotine
      application elicited both intracellular Ca(2+) transients and inward whole-cell
      currents. These responses were mediated by heteromeric nAChRs, as assessed by
      their sensitivity to nicotine and time constant of current decay. Preincubating
      the cells with low melatonin concentrations (down to 1 pm) significantly reduced
      the current amplitude in a dose-dependent manner, without affecting the
      receptor's apparent affinity and voltage-dependency, nor the current's rise and
      decay time course. The inhibitory effect of melatonin was significantly reduced
      by luzindole, a competitive antagonist of both MT(1) and MT(2) melatonin
      receptors. In conclusion, melatonin inhibits nicotinic currents through non
      alpha7 heteromeric nAChRs expressed by CGNs in culture, an effect that appears to
      be at least partially mediated by melatonin membrane receptors. Direct modulation
      of nicotinic receptors is accomplished at doses that are likely to be
      physiologically relevant, thus providing a mechanism through which melatonin
      circadian rhythmic levels could modulate cholinergic activity.

PMID- 18078452
TI  - Signal transduction pathways involved in protective effects of melatonin in C6
      glioma cells.
AB  - Melatonin (N-acetyl-5-methoxytryptamine), an indole hormone, is the chief
      secretory product of the pineal gland and is an efficient free radical scavenger
      and antioxidant, both in vitro and in vivo. The role of melatonin as an
      immunomodulator is, in some cases, contradictory. Although melatonin is reported
      to influence a variety of inflammatory and immune responses, evidence supporting
      its effects on important glioma cells-derived mediators is incomplete. We
      studied, in rat glioma cell line (C6), the role of melatonin (100 microm-1 mm) in
      the regulation of the expression of nitric oxide synthase (NOS) caused by
      incubation with lipopolysaccharide (LPS)/interferon (IFN)-gamma (1 microg/mL and
      100 U/mL, respectively) and defined the mode of melatonin's action. Treatment
      with LPS/IFN-gamma for 24 hr elicited the induction of inducible (iNOS) activity
      as determined by nitrite and nitrate (NO(x)) accumulation in the culture medium.
      Preincubation with melatonin abrogated the mixed cytokines-mediated induction of
      iNOS. The effect of melatonin was concentration-dependent. Moreover, Western blot
      analysis showed that melatonin inhibited LPS/IFN-gamma-induced expression of COX
      2 protein, but not that of constitutive cyclooxygenase. Inhibition of iNOS and
      COX-2 expression was associated with inhibition of activation of the
      transcription factor nuclear factor kappa B (NF-kappaB). The ability of melatonin
      to inhibit NF-kappaB activation was further confirmed by studies on the
      degradation of the inhibitor of NF-kappaB, IkappaB-alpha. Increased production of
      lipid peroxidation products using thiobarbituric acid assay were found in
      cellular contents from activated cultures. Lipid peroxidation was decreased by
      melatonin treatment in a concentration-dependent manner. Moreover, several genes
      having roles in heat-shock response were downregulated in melatonin-treated
      cells, such as 70 proteins, reflecting the reduced oxidative stress in these
      cells. The mechanisms underlying in vitro the neuroprotective properties of
      melatonin involve modulation of transcription factors and consequent altered gene
      expression, resulting in downregulation of inflammation.

PMID- 18078453
TI  - Activation of insulin and IGF-1 signaling pathways by melatonin through MT1
      receptor in isolated rat pancreatic islets.
AB  - Melatonin diminishes insulin release through the activation of MT1 receptors and
      a reduction in cAMP production in isolated pancreatic islets of neonate and adult
      rats and in INS-1 cells (an insulin-secreting cell line). The pancreas of
      pinealectomized rats exhibits degenerative pathological changes with low islet
      density, indicating that melatonin plays a role to ensure the functioning of
      pancreatic beta cells. By using immunoprecipitation and immunoblotting analysis
      we demonstrated, in isolated rat pancreatic islets, that melatonin induces
      insulin growth factor receptor (IGF-R) and insulin receptor (IR) tyrosine
      phosphorylation and mediates the activities of the PI3K/AKT and MEK/ERKs
      pathways, which are involved in cell survival and growth, respectively. Thus, the
      effects of melatonin on pancreatic islets do not involve a reduction in cAMP
      levels only. This indoleamine may regulate growth and differentiation of
      pancreatic islets by activating IGF-I and insulin receptor signaling pathways.

PMID- 18078454
TI  - Melatonin prevents nitric oxide-induced apoptosis by increasing the interaction
      between 14-3-3beta and p-Bad in SK-N-MC cells.
AB  - The anti-apoptotic effect of melatonin has been described in vivo and in vitro. A
      previous report has revealed that melatonin suppresses nitric oxide (NO)-induced
      apoptosis via the induction of Bcl-2 expression in PGT-beta pineal cells. To
      investigate the protective mechanism of melatonin on NO donor S-nitroso-N-acetyl
      penicillamine (SNAP)-induced apoptosis, we examined the anti-apoptotic upstream
      signaling pathway of Bcl-2 in the human neuroblastoma cell line SK-N-MC. The flow
      cytometry results revealed that apoptosis occurred in NO-treated cells, while
      cell death was inhibited by pretreatment with melatonin (100 microm). In
      addition, decreased Bax expression, increased Bcl-2 expression and a decreased
      release of cytochrome c into the cytosol were observed in the melatonin
      pretreated SK-N-MC cells. We also found that melatonin treatment induced the
      activation of Akt/PKB and the phosphorylation of GSK3alpha/beta and Bad.
      Furthermore, melatonin treatment not only increased the protein-protein
      interactions between 14-3-3beta and p-Bad, but also decreased the release of
      cytochrome c from mitochondria into the cytosol. In summary, the protective
      effect of melatonin against NO-induced apoptosis was mediated by the inhibition
      of Bad translocation from the cytosol to the mitochondria by the induction of
      protein-protein interactions between 14-3-3beta and p-Bad.

PMID- 18078455
TI  - Melatonin attenuates the focal cerebral ischemic injury by inhibiting the
      dissociation of pBad from 14-3-3.
AB  - It has recently been reported that melatonin protects neuronal cells from damage
      by enhancing Akt activation, thus mediating antiapoptosis signals. However, there
      is little information regarding the effects of melatonin on the activation of
      genes further downstream in the Akt signaling pathway in ischemic brain injury.
      This study investigated whether melatonin modulates the antiapoptotic signal
      through Akt and its downstream targets, Bad and 14-3-3. Adult male rats were
      treated with melatonin (5 mg/kg) prior to middle cerebral artery occlusion
      (MCAO). Brains were collected at 24 hr after MCAO and infarct volumes were
      analyzed. Our results confirm that melatonin significantly reduces infarct volume
      and decreases the positive reaction of TUNEL staining in the cerebral cortex.
      Signal pathway activation was measured by phosphorylation of Akt at Ser(473) and
      Bad at Ser(136) using Western blot analysis. Melatonin prevented the injury
      induced decrease of pAkt and pBad levels. However, melatonin did not affect the
      expression of 14-3-3, which acts as an antiapoptotic factor through interaction
      with Bad. Immunoprecipitation analysis showed that the interaction between pBad
      and 14-3-3 increased in the presence of melatonin, compared to that of control
      animals. Our findings suggest that melatonin prevents cell death because of brain
      injury and that these protective effects are mediated through maintaining the
      interaction between pBad and 14-3-3, thus blocking activation of the apoptotic
      pathway.

PMID- 18078456
TI  - Intracellular signaling pathways involved in cell growth inhibition of human
      umbilical vein endothelial cells by melatonin.
AB  - Melatonin, an indolamine mainly produced in the pineal gland, has received a
      great deal of attention in the last decade because of its oncostatic effects,
      which are due to its immunomodulatory, antiproliferative, antioxidant and its
      possible antiangiogenesis properties. Herein, we document its antiproliferative
      action on human umbilical vein endothelial cells (HUVECs). Moreover, the possible
      cell signaling pathways when melatonin inhibited HUVEC proliferation were
      explored in this study. Primary HUVECs were isolated, cultured, purified and
      identified before the studies were performed. HUVECs were found to possess G
      protein-coupled membrane receptors for melatonin (MT1 and MT2) and also nuclear
      melatonin receptors (RORalpha and RORbeta, especially RORbeta). No obvious
      expression of RORgamma was found. We investigated the membrane receptors and
      several intracellular signaling pathways including mitogen-activated protein
      kinases (MAPK)/extracellular signal-related kinases (ERK), phosphoinositol-3
      kinase (PI3K)/Akt and protein kinases C (PKC) involved in antiproliferative
      action of melatonin on HUVECs. The blockade of these pathways using special
      inhibitors decreased cell growth. Furthermore, the constitutive activation of
      nuclear factor kappa B (NF-kappaB) contributed to the proliferation of HUVECs.
      High concentrations of melatonin inhibited both NF-kappaB expression and its
      binding ability to DNA, possibly through inactivation of ERK/Akt /PKC pathways.
      Taken together, high concentrations of melatonin markedly reduced HUVEC
      proliferation; the antiproliferative action of melatonin was closely correlated
      with following pathway: melatonin receptors/ERK/PI3K/Akt/PKC/ NF-kappaB.

PMID- 18078458
TI  - Function vs fate?

PMID- 18078460
TI  - Tumour budding at invasive margins and outcome in colorectal cancer.
AB  - OBJECTIVE: Tumour budding, defined as small clusters of undifferentiated cancer
      cells at invasive margins, has been shown to reflect biologic aggressiveness of
      colorectal cancers. We therefore examined the prognostic significance of tumour
      budding in patients with colorectal carcinoma, particularly focusing on
      comparisons with other clinicopathological findings. METHOD: Tumour budding was
      investigated in surgically resected specimens from 159 patients with colorectal
      carcinoma. With haematoxylin and eosin stained slides containing the entire
      invasive margin, the degree of tumour budding was classified into three grades:
      mild, <1/3 of the entire invasive margin; moderate, 1/3-2/3; marked, >2/3.
      RESULTS: Mild tumour budding was found in 54 (34%) cases, moderate in 59 (37%)
      cases and marked in 46 (29%) cases. The degree of budding was linked with poor
      tumour differentiation, lymph node metastasis and advanced TNM stage (P < 0.001).
      In univariate analysis, patients with marked tumour budding [5-year cancer
      related survival (CRS)/recurrence-free survival (RFS), 39%/53%] had significantly
      worse survival [CRS, hazard ratio (HR), 4.561; 95% confidence interval (CI),
      2.265-9.184; P < 0.001; RFS, HR, 3.240; 95% CI, 1.430-7.342; P = 0.005] than
      those with mild (5-year CRS/RFS, 80%/82%) or moderate (63%/66%) budding. In the
      Cox regression model, marked tumour budding (HR, 3.137; 95% CI, 1.517-6.487; P =
      0.002) and advanced tumour stage (stage III, HR, 3.226; 95% CI, 1.475-7.053; P =
      0.003; stage IV, HR, 24.443; 95% CI, 10.843-55.100; P < 0.001) proved to be an
      independent predictor of short CRS. CONCLUSION: Tumour budding is a practical and
      significant histological index for identification of high malignant potential and
      poor outcome in patients with colorectal carcinoma.

PMID- 18078461
TI  - Colorectal MDTs: the team's perspective.
AB  - OBJECTIVE: Multidisciplinary teams (MDTs) are an integral part of the National
      Cancer Plan. However, there is surprisingly little empirical research on how
      these are perceived by colorectal surgeons (CRSs) and colorectal clinical nurse
      specialists (CNSs). The purpose of this study therefore was to obtain the views
      of a national cohort of CRSs and CNSs regarding various important aspects of MDT
      functioning and role of CNS in current setting. METHOD: Two hundred and fifty
      three CRSs and 177 CNSs, identified from the Association of Coloproctologists of
      Great Britain and Ireland, responded to an ad hoc postal questionnaire. RESULTS:
      96.5% of respondents considered that MDTs improved the overall quality of care of
      colorectal cancer patients, and 78.6% thought MDTs were good for their morale.
      Eighty per cent considered that they improved training. Seventy-three per cent of
      surgeons and nurses thought that MDTs were cost effective, and 89% did not
      consider them to be a passing fad. However, more than half (50.4%) of the CRSs
      and 35.2% of the CNSs stated that their job plan did not contain adequate time to
      attend MDT meetings. Compared with CRSs, CNSs were significantly more likely to
      have positive views regarding the MDT (P < 0.005). CONCLUSION: CNSs and CRSs
      consider that colorectal MDTs have very beneficial effects on patient care,
      training and morale. However, many surgeons and nurse specialists consider that
      attendance at MDTs is not taken into account adequately in terms of their job
      plans, and this issue needs to be addressed.

PMID- 18078462
TI  - An unusual case of right iliac fossa mass--Pharmacobezoar mimicking inflammatory
      bowel disease.

PMID- 18078467
TI  - Remembrances of an embryo: long-term effects on phenology traits in spruce.

PMID- 18078468
TI  - C4 leaf curling--coupling incident light, stomatal and photosynthetic
      asymmetries.

PMID- 18078469
TI  - Plant disease and global change--the importance of long-term data sets.

PMID- 18078470
TI  - Systems biology and the biology of systems: how, if at all, are they related?

PMID- 18078471
TI  - Evolution of the type III secretion system and its effectors in plant-microbe
      interactions.
AB  - Many bacterial plant pathogens require the type III secretion system (T3SS) and
      its effector proteins (T3SEs) to invade and extract nutrients from their hosts
      successfully. While the molecular function of this system is being studied
      intensively, we know comparatively little about the evolutionary and ecological
      pressures governing its fate over time, and even less about the detailed
      mechanisms underlying and driving complex T3SS-mediated coevolutionary dynamics.
      In this review we summarize our current understanding of how host-pathogen
      interactions evolve, with a particular focus on the T3SS of bacterial plant
      pathogens. We explore the evolutionary origins of the T3SS relative to the
      closely related flagellar system, and investigate the evolutionary pressures on
      this secretion and translocation apparatus. We examine the evolutionary forces
      acting on T3SEs, and compare the support for vertical descent with modification
      of these virulence-associated systems (pathoadaptation) vs horizontal gene
      transfer. We address the evolutionary origins of T3SEs from the perspective of
      both the evolutionary mechanisms that generate new effectors, and the mobile
      elements that may be the source of novel genetic material. Finally, we propose a
      number of questions raised by these studies, which may serve to guide our
      thinking about these complex processes.

PMID- 18078472
TI  - Reduced gibberellin response affects ethylene biosynthesis and responsiveness in
      the Arabidopsis gai eto2-1 double mutant.
AB  - Ethylene and gibberellins (GAs) control similar developmental processes in
      plants. The role of ethylene is at least in part to regulate the accumulation of
      DELLA proteins, key regulators of plant growth, which suppress the GA response.
      To expand our knowledge of ethylene-GA crosstalk and to reveal how the modulation
      of the ethylene and GA pathways affects global plant growth, the gibberellin
      insensitive (gai), ethylene-overproducing 2-1 (eto2-1) double mutant, which has
      decreased GA signalling (resulting from gai) and increased ethylene biosynthesis
      (resulting from eto2-1), was characterized. Both single mutations resulted in
      reduced elongation growth. The double mutant showed synergistic responses in root
      and shoot growth, in induction of floral transition, and in inflorescence length,
      showing that crosstalk between the two pathways occurs in different plant organs
      throughout development. Furthermore, the altered ethylene-GA interactions
      affected root-shoot communication, as evidenced by an enhanced shoot:root ratio
      in the double mutant. When compared with both single mutants and the wild type,
      double mutants had enhanced content of active GA(4) at both the seedling and the
      rosette stages, and, unlike the gai mutant, they were sensitive to GA treatment.
      Finally, it was shown that synergistic responses in the double mutant were not
      caused by elevated ethylene biosynthesis but that, in the light, enhanced
      sensitivity to ethylene may, at least in part, be responsible for the observed
      phenotype.

PMID- 18078474
TI  - Drugs and the kidney: more than a question of dose.

PMID- 18078476
TI  - Carbamazepine-induced urinary retention.

PMID- 18078475
TI  - The effect of screening for cardio-renal risk factors on drug use in the general
      population.
AB  - AIM: To evaluate the effect of a cardio-renal screening programme on desired and
      undue drug use. METHODS: Data from the PREVEND cohort (Prevention of REnal and
      Vascular ENd-stage Disease) were used. The drug use of screened (randomly)
      selected subjects (n = 2650) was compared with unscreened subjects, matched for
      age and sex (n = 10 434). Drug use in the overall PREVEND cohort, enriched for
      albuminuria (n = 6751), was also studied. Screening-related drugs
      (antihypertensive, antilipidaemic, antidiabetic and antithrombotic) were
      selected, as well as screening-unrelated drugs (benzodiazepines, drugs for acid
      related disorders and painkillers). Time to first prescription after screening is
      presented as Kaplan-Meier curves. RESULTS: After 6.5 years of follow-up, the
      incidence of drug use was not significantly different between the screened,
      randomly selected and unscreened cohorts. Antihypertensives were used by 21.5 and
      20.8%, respectively; antilipidaemic 12.8 and 10.2%, antidiabetics 4.0 and 3.9%,
      and antithrombotic 11.4 and 12.0%. Screening-unrelated drugs were used at
      comparable frequencies. Compared with the unscreened cohort, screening-related
      drugs were prescribed more frequently for subjects in the enriched cohort (25.8,
      15.5, 5.5 and 13.5% for antihypertensive, antilipidaemic, antidiabetic and
      antithrombotic, respectively), whereas screening-unrelated drugs were used at
      comparable frequencies. CONCLUSIONS: The incidence of drug use did not differ
      between the screened, randomly selected and unscreened cohorts. Screening does
      not lead to more drug prescription, thus arguing against the fear of undue
      medicalization after screening. The data also show that, for screening to be
      successful, it should be performed in a targeted population, such as one enriched
      for albuminuria.

PMID- 18078477
TI  - Line transect methods for plant surveys.
AB  - Interest in surveys for monitoring plant abundance is increasing, due in part to
      the need to quantify the rate of loss of biodiversity. Line transect sampling
      offers an efficient way to monitor many species. However, the method does not
      work well in some circumstances, for example on small survey plots, when the
      plant species has a strongly aggregated distribution, or when plants that are on
      the line are not easily detected. We develop a crossed design, together with
      methods that exploit the additional information from such a design, to address
      these problems. The methods are illustrated using data on a colony of cowslips.

PMID- 18078478
TI  - Regression analysis of panel count data with dependent observation times.
AB  - Panel count data often occur in long-term studies that concern occurrence rate of
      a recurrent event. Methods have been proposed for regression analysis of panel
      count data, but most of the existing research focuses on situations where
      observation times are independent of longitudinal response variables and
      therefore rely on conditional inference procedures given the observation times.
      This article considers a different situation where the independence assumption
      may not hold. That is, the observation times and the response variable may be
      correlated. For inference, estimating equation approaches are proposed for
      estimation of regression parameters and both large and finite sample properties
      of the proposed estimates are established. An illustrative example from a cancer
      study is provided.

PMID- 18078479
TI  - A class of markov models for longitudinal ordinal data.
AB  - Generalized linear models with serial dependence are often used for short
      longitudinal series. Heagerty (2002, Biometrics58, 342-351) has proposed
      marginalized transition models for the analysis of longitudinal binary data. In
      this article, we extend this work to accommodate longitudinal ordinal data.
      Fisher-scoring algorithms are developed for estimation. Methods are illustrated
      on quality-of-life data from a recent colorectal cancer clinical trial.

PMID- 18078480
TI  - Semiparametric regression of multidimensional genetic pathway data: least-squares
      kernel machines and linear mixed models.
AB  - We consider a semiparametric regression model that relates a normal outcome to
      covariates and a genetic pathway, where the covariate effects are modeled
      parametrically and the pathway effect of multiple gene expressions is modeled
      parametrically or nonparametrically using least-squares kernel machines (LSKMs).
      This unified framework allows a flexible function for the joint effect of
      multiple genes within a pathway by specifying a kernel function and allows for
      the possibility that each gene expression effect might be nonlinear and the genes
      within the same pathway are likely to interact with each other in a complicated
      way. This semiparametric model also makes it possible to test for the overall
      genetic pathway effect. We show that the LSKM semiparametric regression can be
      formulated using a linear mixed model. Estimation and inference hence can proceed
      within the linear mixed model framework using standard mixed model software. Both
      the regression coefficients of the covariate effects and the LSKM estimator of
      the genetic pathway effect can be obtained using the best linear unbiased
      predictor in the corresponding linear mixed model formulation. The smoothing
      parameter and the kernel parameter can be estimated as variance components using
      restricted maximum likelihood. A score test is developed to test for the genetic
      pathway effect. Model/variable selection within the LSKM framework is discussed.
      The methods are illustrated using a prostate cancer data set and evaluated using
      simulations.

PMID- 18078481
TI  - Conditional likelihood methods for haplotype-based association analysis using
      matched case-control data.
AB  - Genetic epidemiologists routinely assess disease susceptibility in relation to
      haplotypes, that is, combinations of alleles on a single chromosome. We study
      statistical methods for inferring haplotype-related disease risk using single
      nucleotide polymorphism (SNP) genotype data from matched case-control studies,
      where controls are individually matched to cases on some selected factors.
      Assuming a logistic regression model for haplotype-disease association, we
      propose two conditional likelihood approaches that address the issue that
      haplotypes cannot be inferred with certainty from SNP genotype data (phase
      ambiguity). One approach is based on the likelihood of disease status conditioned
      on the total number of cases, genotypes, and other covariates within each
      matching stratum, and the other is based on the joint likelihood of disease
      status and genotypes conditioned only on the total number of cases and other
      covariates. The joint-likelihood approach is generally more efficient,
      particularly for assessing haplotype-environment interactions. Simulation studies
      demonstrated that the first approach was more robust to model assumptions on the
      diplotype distribution conditioned on environmental risk variables and matching
      factors in the control population. We applied the two methods to analyze a
      matched case-control study of prostate cancer.

PMID- 18078482
TI  - Tail posterior probability for inference in pairwise and multiclass gene
      expression data.
AB  - We consider the problem of identifying differentially expressed genes in
      microarray data in a Bayesian framework with a noninformative prior distribution
      on the parameter quantifying differential expression. We introduce a new rule,
      tail posterior probability, based on the posterior distribution of the
      standardized difference, to identify genes differentially expressed between two
      conditions, and we derive a frequentist estimator of the false discovery rate
      associated with this rule. We compare it to other Bayesian rules in the
      considered settings. We show how the tail posterior probability can be extended
      to testing a compound null hypothesis against a class of specific alternatives in
      multiclass data.

PMID- 18078483
TI  - Analysis of pulsatile hormone concentration profiles with nonconstant Basal
      concentration: a bayesian approach.
AB  - Many challenges arise in the analysis of pulsatile, or episodic, hormone
      concentration time series data. Among these challenges is the determination of
      the number and location of pulsatile events and the discrimination of events from
      noise. Analyses of these data are typically performed in two stages. In the first
      stage, the number and approximate location of the pulses are determined. In the
      second stage, a model (typically a deconvolution model) is fit to the data
      conditional on the number of pulses. Any error made in the first stage is carried
      over to the second stage. Furthermore, current methods, except two, assume that
      the underlying basal concentration is constant. We present a fully Bayesian
      deconvolution model that simultaneously estimates the number of secretion
      episodes, as well as their locations, and a nonconstant basal concentration. This
      model obviates the need to determine the number of events a priori. Furthermore,
      we estimate probabilities for all "candidate" event locations. We demonstrate our
      method on a real data set.

PMID- 18078484
TI  - Shared uncertainty in measurement error problems, with application to Nevada Test
      Site fallout data.
AB  - In radiation epidemiology, it is often necessary to use mathematical models in
      the absence of direct measurements of individual doses. When complex models are
      used as surrogates for direct measurements to estimate individual doses that
      occurred almost 50 years ago, dose estimates will be associated with considerable
      error, this error being a mixture of (a) classical measurement error due to
      individual data such as diet histories and (b) Berkson measurement error
      associated with various aspects of the dosimetry system. In the Nevada Test
      Site(NTS) Thyroid Disease Study, the Berkson measurement errors are correlated
      within strata. This article concerns the development of statistical methods for
      inference about risk of radiation dose on thyroid disease, methods that account
      for the complex error structure inherence in the problem. Bayesian methods using
      Markov chain Monte Carlo and Monte-Carlo expectation-maximization methods are
      described, with both sharing a key Metropolis-Hastings step. Regression
      calibration is also considered, but we show that regression calibration does not
      use the correlation structure of the Berkson errors. Our methods are applied to
      the NTS Study, where we find a strong dose-response relationship between dose and
      thyroiditis. We conclude that full consideration of mixtures of Berkson and
      classical uncertainties in reconstructed individual doses are important for
      quantifying the dose response and its credibility/confidence interval. Using
      regression calibration and expectation values for individual doses can lead to a
      substantial underestimation of the excess relative risk per gray and its 95%
      confidence intervals.

PMID- 18078485
TI  - A proportional hazards cure model for the analysis of time to event with
      frequently unidentifiable causes.
AB  - We propose a semiparametric method for the analysis of masked-cause failure data
      that are also subject to a cure. We present estimators for the failure time
      distribution, the cure rate, and the covariate effect on each of these, assuming
      a proportional hazards cure model for the time to event of interest and we use
      the expectation-maximization algorithm to conduct the likelihood maximization.
      The method is applied to data from a breast cancer clinical trial.

PMID- 18078486
TI  - Exact sample size needed to detect dependence in 2 x 2 x 2 tables.
AB  - In the Georgia Centenarian Study (Poon et al., Exceptional Longevity, 2006),
      centenarian cases and young controls are classified according to three categories
      (age, ethnic origin, and single nucleotide polymorphisms [SNPs] of candidate
      longevity genes), where each factor has two possible levels. Here we provide
      methodologies to determine the minimum sample size needed to detect dependence in
      2 x 2 x 2 tables based on Fisher's exact test evaluated exactly or by Markov
      chain Monte Carlo (MCMC), assuming only the case total L and the control total N
      are known. While our MCMC method uses serial computing, parallel computing
      techniques are employed to solve the exact sample size problem. These tools will
      allow researchers to design efficient sampling strategies and to select
      informative SNPs. We apply our tools to 2 x 2 x 2 tables obtained from a pilot
      study of the Georgia Centenarians Study, and the sample size results provided
      important information for the subsequent major study. A comparison between the
      results of an exact method and those of a MCMC method showed that the MCMC method
      studied needed much less computation time on average (10.16 times faster on
      average for situations examined with S.E. = 2.60), but its sample size results
      were only valid as a rule for larger sample sizes (in the hundreds).

PMID- 18078503
TI  - MIRIAM Resources: tools to generate and resolve robust cross-references in
      Systems Biology.
AB  - BACKGROUND: The Minimal Information Requested In the Annotation of biochemical
      Models (MIRIAM) is a set of guidelines for the annotation and curation processes
      of computational models, in order to facilitate their exchange and reuse. An
      important part of the standard consists in the controlled annotation of model
      components, based on Uniform Resource Identifiers. In order to enable
      interoperability of this annotation, the community has to agree on a set of
      standard URIs, corresponding to recognised data types. MIRIAM Resources are being
      developed to support the use of those URIs. RESULTS: MIRIAM Resources are a set
      of on-line services created to catalogue data types, their URIs and the
      corresponding physical URLs (or resources), whether data types are controlled
      vocabularies or primary data resources. MIRIAM Resources are composed of several
      components: MIRIAM Database stores the information, MIRIAM Web Services allows to
      programmatically access the database, MIRIAM Library provides an access to the
      Web Services and MIRIAM Web Application is a way to access the data (human
      browsing) and also to edit or add entries. CONCLUSIONS: The project MIRIAM
      Resources allows an easy access to MIRIAM URIs and the associated information and
      is therefore crucial to foster a general use of MIRIAM annotations in
      computational models of biological processes.

PMID- 18078504
TI  - Imparting carrier status results detected by universal newborn screening for
      sickle cell and cystic fibrosis in England: a qualitative study of current
      practice and policy challenges.
AB  - BACKGROUND: Universal newborn screening for early detection of children affected
      by sickle cell disorders and cystic fibrosis is currently being implemented
      across England. Parents of infants identified as carriers of these disorders must
      also be informed of their baby's result. However there is a lack of evidence for
      most effective practice internationally when doing so. This study describes
      current or proposed models for imparting this information in practice and
      explores associated challenges for policy. METHODS: Thematic analysis of semi
      structured interviews with Child Health Coordinators from all English Health
      Regions. RESULTS: Diverse methods for imparting carrier results, both within and
      between regions, and within and between conditions, were being implemented or
      planned. Models ranged from result by letter to in-person communication during a
      home visit. Non-specialists were considered the best placed professionals to give
      results and a similar approach for both conditions was emphasised. While national
      guidance has influenced choice of models, other factors contributed such as
      existing service structures and lack of funding. Challenges included uncertainty
      about guidance specifying face to face notification; how best to balance allaying
      parental anxiety by using familiar non-specialist health professionals with
      concerns about practitioner competence; and extent of information parents should
      be given. Inadequate consideration of resource and service workload was seen as
      the main policy obstacle. Clarification of existing guidance; more specific
      protocols to ensure consistent countrywide practice; integration of the two
      programmes; and 'normalising' carrier status were suggested as improvements.
      CONCLUSION: Differing models for communicating carrier results raise concerns
      about equity and clinical governance. However, this variation provides
      opportunity for evaluation. Timely and more detailed guidance on protocols with
      clarification of existing recommendations is needed.

PMID- 18078505
TI  - The training needs of Turkish emergency department personnel regarding intimate
      partner violence.
AB  - BACKGROUND: Violence against females is a widespread public health problem in
      Turkey and the lifetime prevalence of IPV ranges between 34 and 58.7%. Health
      care workers (HCW) sometimes have the unique opportunity and obligation to
      identify, treat, and educate females who are abused. The objective of this study
      was to evaluate the knowledge, attitudes, and experiences of the emergency
      department (ED) staff regarding intimate partner violence (IPV) at a large
      university hospital in Turkey. METHODS: A cross-sectional study was conducted in
      a large university hospital via questionnaire. The study population consisted of
      all the nurses and physicians who worked in the ED during a two month period (n =
      215). The questionnaire response rate was 80.5% (41 nurses and 132 physicians).
      The main domains of the questionnaire were knowledge regarding the definition of
      IPV, clinical findings in victims of IPV, legal aspects of IPV, attitudes towards
      IPV, knowledge about the characteristics of IPV victims and abusers, and
      professional and personal experiences and training with respect to IPV. RESULTS:
      One-half of the study group were females, 76.3% were physicians, and 89.8% had no
      training on IPV. The majority of the nurses (89.5%) and physicians (71.1%)
      declared that they were aware of the clinical appearance of IPV. The mean of the
      knowledge scores on clinical knowledge were 8.84 +/- 1.73 (range, 0-10) for acute
      conditions, and 4.51 +/- 3.32 for chronic conditions. The mean of the knowledge
      score on legal procedures and the legal rights of the victims was 4.33 +/- 1.66
      (range, 0-7). At least one reason to justify physical violence was accepted by
      69.0% of females and 84.7% of males, but more males than females tended to
      justify violence (chi square = 5.96; p = 0.015). However, both genders accepted
      that females who experienced physical violence should seek professional medical
      help. CONCLUSION: The study participants' knowledge about IPV was rather low and
      a training program is thus necessary on this issue. Attention must be given to
      the legal aspects and clinical manifestations of IPV. The training program should
      also include a module on gender roles in order to improve the attitudes towards
      IPV.

PMID- 18078506
TI  - Knee arthroscopy and exercise versus exercise only for chronic patellofemoral
      pain syndrome: a randomized controlled trial.
AB  - BACKGROUND: Arthroscopy is often used to treat patients with chronic
      patellofemoral pain syndrome (PFPS). As there is a lack of evidence, we conducted
      a randomized controlled trial to study the efficacy of arthroscopy in patients
      with chronic PFPS. METHODS: A total of 56 patients with chronic PFPS were
      randomized into two treatment groups: an arthroscopy group (N = 28), treated with
      knee arthroscopy and an 8-week home exercise program, and a control group (N =
      28), treated with the 8-week home exercise program only. The arthroscopy included
      finding-specific surgical procedures according to current recommendations. The
      primary outcome was the Kujala score on patellofemoral pain and function at 9
      months following randomization. Secondary outcomes were visual analog scales
      (VASs) to assess activity-related symptoms. We also estimated the direct
      healthcare costs. RESULTS: Both groups showed marked improvement during the
      follow-up. The mean improvement in the Kujala score was 12.9 (95% confidence
      interval (CI) 8.2-17.6) in the arthroscopy group and 11.4 (95% CI 6.9-15.8) in
      the control group. However, there was no difference between the groups in mean
      improvement in the Kujala score (group difference 1.1 (95% CI -7.4 - 5.2)) or in
      any of the VAS scores. Total direct healthcare costs in the arthroscopy group
      were estimated to exceed on average those of the control group by euro901 per
      patient (p < 0.001). CONCLUSION: In this controlled trial involving patients with
      chronic PFPS, the outcome when arthroscopy was used in addition to a home
      exercise program was no better than when the home exercise program was used
      alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 41800323.

PMID- 18078507
TI  - Part 3. Triethylborane-air: a suitable initiator for intermolecular radical
      additions of S-2-oxoalkyl-thionocarbonates (S-xanthates) to olefins.
AB  - Under carefully controlled conditions, the triethylborane-air combination proves
      to be an efficient radical initiator that allows intermolecular radical additions
      of S-2-oxoalkyl-thionocarbonates (S-xanthates) to olefins. Depending on both the
      structures of the xanthate and the olefin, the addition process can be achieved
      at room temperature or slightly higher.

PMID- 18078508
TI  - Vasopressin in septic shock: effects on pancreatic, renal, and hepatic blood
      flow.
AB  - INTRODUCTION: Vasopressin has been shown to increase blood pressure in
      catecholamine-resistant septic shock. The aim of this study was to measure the
      effects of low-dose vasopressin on regional (hepato-splanchnic and renal) and
      microcirculatory (liver, pancreas, and kidney) blood flow in septic shock.
      METHODS: Thirty-two pigs were anesthetized, mechanically ventilated, and randomly
      assigned to one of four groups (n = 8 in each). Group S (sepsis) and group SV
      (sepsis/vasopressin) were exposed to fecal peritonitis. Group C and group V were
      non-septic controls. After 240 minutes, both septic groups were resuscitated with
      intravenous fluids. After 300 minutes, groups V and SV received intravenous
      vasopressin 0.06 IU/kg per hour. Regional blood flow was measured in the hepatic
      and renal arteries, the portal vein, and the celiac trunk by means of ultrasonic
      transit time flowmetry. Microcirculatory blood flow was measured in the liver,
      kidney, and pancreas by means of laser Doppler flowmetry. RESULTS: In septic
      shock, vasopressin markedly decreased blood flow in the portal vein, by 58% after
      1 hour and by 45% after 3 hours (p < 0.01), whereas flow remained virtually
      unchanged in the hepatic artery and increased in the celiac trunk.
      Microcirculatory blood flow decreased in the pancreas by 45% (p < 0.01) and in
      the kidney by 16% (p < 0.01) but remained unchanged in the liver. CONCLUSION:
      Vasopressin caused marked redistribution of splanchnic regional and
      microcirculatory blood flow, including a significant decrease in portal,
      pancreatic, and renal blood flows, whereas hepatic artery flow remained virtually
      unchanged. This study also showed that increased urine output does not
      necessarily reflect increased renal blood flow.

PMID- 18078509
TI  - Dimerisation of HIV-2 genomic RNA is linked to efficient RNA packaging, normal
      particle maturation and viral infectivity.
AB  - BACKGROUND: Retroviruses selectively encapsidate two copies of their genomic RNA,
      the Gag protein binding a specific RNA motif in the 5' UTR of the genome. In
      human immunodeficiency virus type 2 (HIV-2), the principal packaging signal (Psi)
      is upstream of the major splice donor and hence is present on all the viral RNA
      species. Cotranslational capture of the full length genome ensures specificity.
      HIV-2 RNA dimerisation is thought to occur at the dimer initiation site (DIS)
      located in stem-loop 1 (SL-1), downstream of the main packaging determinant.
      However, the HIV-2 packaging signal also contains a palindromic sequence (pal)
      involved in dimerisation. In this study, we analysed the role of the HIV-2
      packaging signal in genomic RNA dimerisation in vivo and its implication in viral
      replication. RESULTS: Using a series of deletion and substitution mutants in SL-1
      and the Psi region, we show that in fully infectious HIV-2, genomic RNA
      dimerisation is mediated by the palindrome pal. Mutation of the DIS had no effect
      on dimerisation or viral infectivity, while mutations in the packaging signal
      severely reduce both processes as well as RNA encapsidation. Electron micrographs
      of the Psi-deleted virions revealed a significant reduction in the proportion of
      mature particles and an increase in that of particles containing multiple cores.
      CONCLUSION: In addition to its role in RNA encapsidation, the HIV-2 packaging
      signal contains a palindromic sequence that is critical for genomic RNA
      dimerisation. Encapsidation of a dimeric genome seems required for the production
      of infectious mature particles, and provides a promising therapeutic target.

PMID- 18078510
TI  - The effects of neighborhood density and street connectivity on walking behavior:
      the Twin Cities walking study.
AB  - A growing body of health and policy research suggests residential neighborhood
      density and street connectivity affect walking and total physical activity, both
      of which are important risk factors for obesity and related chronic diseases. The
      authors report results from their methodologically novel Twin Cities Walking
      Study; a multilevel study which examined the relationship between built
      environments, walking behavior and total physical activity. In order to maximize
      neighborhood-level variation while maintaining the exchangeability of resident
      subjects, investigators sampled 716 adult persons nested in 36 randomly selected
      neighborhoods across four strata defined on density and street-connectivity - a
      matched sampling design. Outcome measures include two types of self-reported
      walking (from surveys and diaries) and so-called objective 7-day accelerometry
      measures. While crude differences are evident across all outcomes, adjusted
      effects show increased odds of travel walking in higher-density areas and
      increased odds of leisure walking in low-connectivity areas, but neither density
      nor street connectivity are meaningfully related to overall mean miles walked per
      day or increased total physical activity. Contrary to prior research, the authors
      conclude that the effects of density and block size on total walking and physical
      activity are modest to non-existent, if not contrapositive to hypotheses.
      Divergent findings are attributed to this study's sampling design, which tends to
      mitigate residual confounding by socioeconomic status.

PMID- 18078511
TI  - Removal of nucleus pulposus from the intervertebral disc - the use of chymopapain
      enhances mechanical removal with rongeurs: a laboratory study.
AB  - BACKGROUND: A laboratory study was conducted, on cadaveric sheep spines to
      develop an effective procedure for removing as much nucleus as possible from an
      intervertebral disc with minimal disruption to the annulus. The results of many
      studies involving removal of nucleus, including chemonucleolysis, using
      chymopapain, have been published but we are not aware of any previous
      quantitative studies on procedures for removing as much nucleus as possible from
      the disc. METHODS: All procedures were performed via a 3 mm trocar. Four
      procedures were compared: (I) unilateral approach using rongeurs alone, (II)
      bilateral approach using rongeurs alone, (III) unilateral approach using rongeurs
      followed by chymopapain and (IV) bilateral approach using rongeurs followed by
      chymopapain. RESULTS: The percentages of nucleus removed were: (I) 34%, (II) 41%,
      (III) 52% and (IV) 75%; there were significant differences between the four sets
      of results according to ANOVA. CONCLUSION: Significantly more nucleus is removed
      using a bilateral than a unilateral approach; significantly more nucleus is
      removed if chymopapain is used in addition to rongeurs. A brush is useful in
      removing strands of nucleus loosened by chymopapain.

PMID- 18078512
TI  - Activation of HIV-1 expression and replication by cGMP dependent protein kinase
      type 1-beta (PKG1beta).
AB  - The effect of cGMP (cyclic GMP) dependent protein kinase 1-beta (PKG1-beta) and
      cGMP analogues on transcriptional activity and replication of human
      immunodeficiency virus type 1 (HIV-1) was investigated. Transfection of PKG1beta
      expression plasmid increased expression from an HIV-1 LTR-reporter as well as
      from an infectious HIV-1 molecular clone, pNL4-3. Treatment of HIV-1 AD8-infected
      monocyte derived macrophages (MDMs) with cGMP agonists and cGMP antagonists
      caused respectively increased and decreased virus replication. These findings
      provide evidence that cGMP and PKG serve to regulate HIV-1 infection in human
      cells.

PMID- 18078513
TI  - Positional bias of general and tissue-specific regulatory motifs in mouse gene
      promoters.
AB  - BACKGROUND: The arrangement of regulatory motifs in gene promoters, or promoter
      architecture, is the result of mutation and selection processes that have
      operated over many millions of years. In mammals, tissue-specific transcriptional
      regulation is related to the presence of specific protein-interacting DNA motifs
      in gene promoters. However, little is known about the relative location and
      spacing of these motifs. To fill this gap, we have performed a systematic search
      for motifs that show significant bias at specific promoter locations in a large
      collection of housekeeping and tissue-specific genes. RESULTS: We observe that
      promoters driving housekeeping gene expression are enriched in particular motifs
      with strong positional bias, such as YY1, which are of little relevance in
      promoters driving tissue-specific expression. We also identify a large number of
      motifs that show positional bias in genes expressed in a highly tissue-specific
      manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4
      motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as
      many potentially novel regulatory motifs. Based on this analysis, we provide
      predictions for 559 tissue-specific motifs in mouse gene promoters. CONCLUSION:
      The study shows that motif positional bias is an important feature of mammalian
      proximal promoters and that it affects both general and tissue-specific motifs.
      Motif positional constraints define very distinct promoter architectures
      depending on breadth of expression and type of tissue.

PMID- 18078514
TI  - Quantification of global transcription patterns in prokaryotes using spotted
      microarrays.
AB  - We describe an analysis, applicable to any spotted microarray dataset produced
      using genomic DNA as a reference, that quantifies prokaryotic levels of mRNA on a
      genome-wide scale. Applying this to Mycobacterium tuberculosis, we validate the
      technique, show a correlation between level of expression and biological
      importance, define the complement of invariant genes and analyze absolute levels
      of expression by functional class to develop ways of understanding an organism's
      biology without comparison to another growth condition.

PMID- 18078515
TI  - Anticlusterin treatment of breast cancer cells increases the sensitivities of
      chemotherapy and tamoxifen and counteracts the inhibitory action of dexamethasone
      on chemotherapy-induced cytotoxicity.
AB  - INTRODUCTION: Overexpression of the apoptosis-related protein clusterin is
      associated with breast cancer development and tumor progression. We describe the
      use of clusterin-specific antisense oligonucleotides and antibodies to sensitize
      breast carcinoma cells to anticancer drugs routinely used in breast cancer
      therapy. METHODS: MCF-7 and MDA-MB-231 cells were treated with the
      oligonucleotide or antibody, chemotherapeutic agents (doxorubicin or paclitaxel),
      tamoxifen, or with combinations of these. RESULTS: Treatments that include
      antisense clusterin oligonucleotide or antibody to clusterin have been shown to
      reduce the number of viable cells more effectively than treatment with the drugs
      alone. We also demonstrate that dexamethasone pretreatment of breast cancer cell
      lines inhibits chemotherapy-induced cytotoxicity and is associated with the
      transcriptional induction of clusterin. However, anticlusterin treatment
      increases chemotherapy-induced cytotoxicity, even in the presence of
      glucocorticoids, suggesting a possible role for these proteins in glucocorticoid
      mediated survival. CONCLUSION: These data suggest that combined treatment with
      antibodies to clusterin or antisense clusterin oligodeoxynucleotides and
      paclitaxel, doxorubicin, or tamoxifen could be a novel and attractive strategy to
      inhibit the progression of breast carcinoma by regulation of the clusterin
      function. Moreover, glucocorticoid activation in breast cancer cells regulates
      survival signaling by the direct transactivation of genes like clusterin which
      encode proteins that decrease susceptibility to apoptosis. Given the widespread
      clinical administration of dexamethasone before chemotherapy, understanding
      glucocorticoid-induced survival mechanisms is essential for achieving optimal
      therapeutic responses.

PMID- 18078516
TI  - Systematics and plastid genome evolution of the cryptically photosynthetic
      parasitic plant genus Cuscuta (Convolvulaceae).
AB  - BACKGROUND: The genus Cuscuta L. (Convolvulaceae), commonly known as dodders, are
      epiphytic vines that invade the stems of their host with haustorial feeding
      structures at the points of contact. Although they lack expanded leaves, some
      species are noticeably chlorophyllous, especially as seedlings and in maturing
      fruits. Some species are reported as crop pests of worldwide distribution,
      whereas others are extremely rare and have local distributions and apparent niche
      specificity. A strong phylogenetic framework for this large genus is essential to
      understand the interesting ecological, morphological and molecular phenomena that
      occur within these parasites in an evolutionary context. RESULTS: Here we present
      a well-supported phylogeny of Cuscuta using sequences of the nuclear ribosomal
      internal transcribed spacer and plastid rps2, rbcL and matK from representatives
      across most of the taxonomic diversity of the genus. We use the phylogeny to
      interpret morphological and plastid genome evolution within the genus. At least
      three currently recognized taxonomic sections are not monophyletic and subgenus
      Cuscuta is unequivocally paraphyletic. Plastid genes are extremely variable with
      regards to evolutionary constraint, with rbcL exhibiting even higher levels of
      purifying selection in Cuscuta than photosynthetic relatives. Nuclear genome size
      is highly variable within Cuscuta, particularly within subgenus Grammica, and in
      some cases may indicate the existence of cryptic species in this large clade of
      morphologically similar species. CONCLUSION: Some morphological characters
      traditionally used to define major taxonomic splits within Cuscuta are
      homoplastic and are of limited use in defining true evolutionary groups.
      Chloroplast genome evolution seems to have evolved in a punctuated fashion, with
      episodes of loss involving suites of genes or tRNAs followed by stabilization of
      gene content in major clades. Nearly all species of Cuscuta retain some
      photosynthetic ability, most likely for nutrient apportionment to their seeds,
      while complete loss of photosynthesis and possible loss of the entire chloroplast
      genome is limited to a single small clade of outcrossing species found primarily
      in western South America.

PMID- 18078517
TI  - HTLV-1 HBZ cooperates with JunD to enhance transcription of the human telomerase
      reverse transcriptase gene (hTERT).
AB  - BACKGROUND: Activation of telomerase is a critical and late event in tumor
      progression. Thus, in patients with adult-T cell leukaemia (ATL), an HTLV-1
      (Human T cell Leukaemia virus type 1)-associated disease, leukemic cells display
      a high telomerase activity, mainly through transcriptional up-regulation of the
      human telomerase catalytic subunit (hTERT). The HBZ (HTLV-1 bZIP) protein coded
      by the minus strand of HTLV-1 genome and expressed in ATL cells has been shown to
      increase the transcriptional activity of JunD, an AP-1 protein. The presence of
      several AP-1 binding sites in the hTERT promoter led us to investigate whether
      HBZ regulates hTERT gene transcription. RESULTS: Here, we demonstrate using co
      transfection assays that HBZ in association with JunD activates the hTERT
      promoter. Interestingly, the -378/+1 proximal region, which does not contain any
      AP-1 site was found to be responsible for this activation. Furthermore, an
      increase of hTERT transcripts was observed in cells co-expressing HBZ and JunD.
      Chromatin immunoprecipitation (ChIP) assays revealed that HBZ, and JunD coexist
      in the same DNA-protein complex at the proximal region of hTERT promoter.
      Finally, we provide evidence that HBZ/JunD heterodimers interact with Sp1
      transcription factors and that activation of hTERT transcription by these
      heterodimers is mediated through GC-rich binding sites for Sp1 present in the
      proximal sequences of the hTERT promoter. CONCLUSION: These observations
      establish for the first time that HBZ by intervening in the re-activation of
      telomerase, may contribute to the development and maintenance of the leukemic
      process.

PMID- 18078519
TI  - Percutaneous ultrasound-guided ablation of BW7756-hepatoma using ethanol or
      acetic acid in a rat model.
AB  - BACKGROUND: To compare tumor necrosis in hepatoma induced in rats by a single
      percutaneous injection of ethanol (PEI) or acetic acid (PAI). METHODS: BW7756
      hepatomas of 1 mm3 were implanted in the liver of 40 male healthy rats. After 14
      days, the 36 surviving rats were treated, in a single session, by ultrasound
      guided injection of 300 microl of 95% ethanol (n = 17) or 100 microl of 50%
      acetic acid (n = 19). They were sacrificed 14 days after treatment and explanted
      tumoral livers were examined. The same PAI procedure was repeated on 13
      additional rats to exclude a suspected occurrence of technical failures during
      the experiment, due to a surprisingly high rate of deaths within 30 minutes after
      PAI. RESULTS: Four rats died within four days after tumor implantation; after
      PEI, 1/17 (6%) died, whereas after PAI 9/19 (47%) died. The remaining 26 rats,
      after 14 days post-percutaneous ablation, were sacrificed. Gross and microscopic
      examinations showed that the hepatoma's nodules treated with PEI had 45.3 +/-
      19.4% tumor necrosis compared to 49 +/- 23.3% (P = NS) for those treated with
      PAI. Complete tumor necrosis was not found in any animal. Peritoneal invasion was
      present in 4/16 (25%) and 2/10 (20%) rats treated with PEI or PAI, respectively
      (P = NS). Autopsy was performed in the 5 additional rats that died within 30
      minutes after PAI. CONCLUSION: Our results show that there is no significant
      difference in the percentage of tumor necrosis between two local ablation methods
      in spite of the different dosages used. However, mortality in the PAI-treated
      group was greater than in PEI-treated group, presumably due to greater acetic
      acid systemic diffusion and its metabolic side effects. In human subjects, HCC
      occurs in the setting of cirrhosis, where the non-tumoral tissue is firmer than
      the tumor structure, with consequent reduction of drug diffusion. This could be
      the reason why some human studies have concluded similar or even better safety
      and efficacy with PAI compared to PEI.

PMID- 18078518
TI  - Hox, Wnt, and the evolution of the primary body axis: insights from the early
      divergent phyla.
AB  - The subkingdom Bilateria encompasses the overwhelming majority of animals,
      including all but four early-branching phyla: Porifera, Ctenophora, Placozoa, and
      Cnidaria. On average, these early-branching phyla have fewer cell types, tissues,
      and organs, and are considered to be significantly less specialized along their
      primary body axis. As such, they present an attractive outgroup from which to
      investigate how evolutionary changes in the genetic toolkit may have contributed
      to the emergence of the complex animal body plans of the Bilateria. This review
      offers an up-to-date glimpse of genome-scale comparisons between bilaterians and
      these early-diverging taxa. Specifically, we examine these data in the context of
      how they may explain the evolutionary development of primary body axes and axial
      symmetry across the Metazoa. Next, we re-evaluate the validity and evolutionary
      genomic relevance of the zootype hypothesis, which defines an animal by a
      specific spatial pattern of gene expression. Finally, we extend the hypothesis
      that Wnt genes may be the earliest primary body axis patterning mechanism by
      suggesting that Hox genes were co-opted into this patterning network prior to the
      last common ancestor of cnidarians and bilaterians.

PMID- 18078520
TI  - Maximal exercise test is a useful method for physical capacity and oxygen
      consumption determination in streptozotocin-diabetic rats.
AB  - BACKGROUND: The aim of the present study was to investigate the relationship
      between speed during maximum exercise test (ET) and oxygen consumption (VO2) in
      control and STZ-diabetic rats, in order to provide a useful method to determine
      exercise capacity and prescription in researches involving STZ-diabetic rats.
      METHODS: Male Wistar rats were divided into two groups: control (CG, n = 10) and
      diabetic (DG, n = 8). The animals were submitted to ET on treadmill with
      simultaneous gas analysis through open respirometry system. ET and VO2 were
      assessed 60 days after diabetes induction (STZ, 50 mg/Kg). RESULTS: VO2 maximum
      was reduced in STZ-diabetic rats (72.5 +/- 1 mL/Kg/min-1) compared to CG rats
      (81.1 +/- 1 mL/Kg/min-1). There were positive correlations between ET speed and
      VO2 (r = 0.87 for CG and r = 0.8 for DG), as well as between ET speed and VO2
      reserve (r = 0.77 for CG and r = 0.7 for DG). Positive correlations were also
      obtained between measured VO2 and VO2 predicted values (r = 0.81 for CG and r =
      0.75 for DG) by linear regression equations to CG (VO2 = 1.54 * ET speed + 52.34)
      and DG (VO2 = 1.16 * ET speed + 51.99). Moreover, we observed that 60% of ET
      speed corresponded to 72 and 75% of VO2 reserve for CG and DG, respectively. The
      maximum ET speed was also correlated with VO2 maximum for both groups (CG: r =
      0.7 and DG: r = 0.7). CONCLUSION: These results suggest that: a) VO2 and VO2
      reserve can be estimated using linear regression equations obtained from
      correlations with ET speed for each studied group; b) exercise training can be
      prescribed based on ET in control and diabetic-STZ rats; c) physical capacity can
      be determined by ET. Therefore, ET, which involves a relatively simple
      methodology and low cost, can be used as an indicator of cardio-respiratory
      capacity in future studies that investigate the physiological effect of acute or
      chronic exercise in control and STZ-diabetic male rats.

PMID- 18078521
TI  - In vitro secretion profiles of interleukin (IL)-1beta, IL-6, IL-8, IL-10, and TNF
      alpha after selective infection with Escherichia coli in human fetal membranes.
AB  - BACKGROUND: Chorioamniotic membranes infection is a pathologic condition in which
      an abnormal secretion of proinflammatory cytokines halts fetal immune tolerance.
      The aim of the present study was to evaluate the functional response of human
      chorioamniotic membranes, as well as the individual contribution of the amnion
      and choriodecidua after stimulation with Escherichia coli, a pathogen associated
      with preterm labor. METHODS: Explants of chorioamniotic membranes from 10 women
      (37-40 weeks of gestation) were mounted and cultured in a Transwell system, which
      allowed us to test the amnion and choriodecidua compartments independently.
      Escherichia coli (1 x 10 6 CFU/mL) was added to either the amniotic or the
      choriodecidual regions or both; after a 24-h incubation, the secretion of IL
      1beta, IL-6, TNFalpha, IL-8, and IL-10 in both compartments was measured using a
      specific ELISA. Data were analyzed by Kruskal-Wallis one-way analysis of
      variance. RESULTS: After stimulation with Escherichia coli, the choriodecidua
      compartment showed an increase in the secretion of IL-1beta (21-fold), IL-6 (2
      fold), IL-8 (6-fold), and IL-10 (37-fold), regardless of which side of the
      membrane was stimulated; TNFalpha secretion augmented (22-fold) also but only
      when the stimulus was applied simultaneously to both sides. When the amnion was
      stimulated directly, the level of IL-1beta (13-fold) rose significantly; however,
      the increase in IL-8 secretion was larger (20-fold), regardless of the primary
      site of infection. TNFalpha secretion in the amnion compartment rose markedly
      only when Escherichia coli was simultaneously applied to both sides. CONCLUSION:
      Selective stimulation of fetal membranes with Escherichia coli results in a
      differential production of IL-1beta, IL-6, TNFalpha, IL-8, and IL-10. These
      tissues were less responsive when the amnion side was stimulated. This is in
      agreement with the hypothesis that the choriodecidua may play a primary role
      during an ascending intrauterine infection, being the main barrier to progression
      of the infection into the amniotic cavity. Therefore, the tissue-specific
      capacities for the secretion of these immune modulators could be a determining
      factor for the degree of severity of the inflammation process in fetal membranes.

PMID- 18078522
TI  - Mining data from hemodynamic simulations via Bayesian emulation.
AB  - BACKGROUND: Arterial geometry variability is inevitable both within and across
      individuals. To ensure realistic prediction of cardiovascular flows, there is a
      need for efficient numerical methods that can systematically account for
      geometric uncertainty. METHODS AND RESULTS: A statistical framework based on
      Bayesian Gaussian process modeling was proposed for mining data generated from
      computer simulations. The proposed approach was applied to analyze the influence
      of geometric parameters on hemodynamics in the human carotid artery bifurcation.
      A parametric model in conjunction with a design of computer experiments strategy
      was used for generating a set of observational data that contains the maximum
      wall shear stress values for a range of probable arterial geometries. The dataset
      was mined via a Bayesian Gaussian process emulator to estimate: (a) the influence
      of key parameters on the output via sensitivity analysis, (b) uncertainty in
      output as a function of uncertainty in input, and (c) which settings of the input
      parameters result in maximum and minimum values of the output. Finally, potential
      diagnostic indicators were proposed that can be used to aid the assessment of
      stroke risk for a given patient's geometry.

PMID- 18078523
TI  - Direct selection and phage display of a Gram-positive secretome.
AB  - Surface, secreted and transmembrane protein-encoding open reading frames,
      collectively the secretome, can be identified in bacterial genome sequences using
      bioinformatics. However, functional analysis of translated secretomes is possible
      only if many secretome proteins are expressed and purified individually. We have
      now developed and applied a phage display system for direct selection,
      identification, expression and purification of bacterial secretome proteins.

PMID- 18078524
TI  - Gene expression profile in obesity and type 2 diabetes mellitus.
AB  - Obesity is an important component of metabolic syndrome X and predisposes to the
      development of type 2 diabetes mellitus. The incidence of obesity, type 2
      diabetes mellitus and metabolic syndrome X is increasing, and the cause(s) for
      this increasing incidence is not clear. Although genetics could play an important
      role in the higher prevalence of these diseases, it is not clear how genetic
      factors interact with environmental and dietary factors to increase their
      incidence. We performed gene expression profile in subjects with obesity and type
      2 diabetes mellitus with and without family history of these diseases. It was
      noted that genes involved in carbohydrate, lipid and amino acid metabolism
      pathways, glycan of biosynthesis, metabolism of cofactors and vitamin pathways,
      ubiquitin mediated proteolysis, signal transduction pathways, neuroactive ligand
      receptor interaction, nervous system pathways, neurodegenerative disorders
      pathways are upregulated in obesity compared to healthy subjects. In contrast
      genes involved in cell adhesion molecules, cytokine-cytokine receptor
      interaction, insulin signaling and immune system pathways are downregulated in
      obese. Genes involved in signal transduction, regulation of actin cytoskeleton,
      antigen processing and presentation, complement and coagulation cascades, axon
      guidance and neurodegenerative disorders pathways are upregulated in subjects
      with type 2 diabetes with family history of diabetes compared to those who are
      diabetic but with no family history. Genes involved in oxidative phosphorylation,
      immune, nervous system, and metabolic disorders pathways are upregulated in those
      with diabetes with family history of diabetes compared to those with diabetes but
      with no family history. In contrast, genes involved in lipid and amino acid
      pathways, ubiquitin mediated proteolysis, signal transduction, insulin signaling
      and PPAR signaling pathways are downregulated in subjects with diabetes with
      family history of diabetes. It was noted that genes involved in inflammatory
      pathway are differentially expressed both in obesity and type 2 diabetes. These
      results suggest that genes concerned with carbohydrate, lipid and amino acid
      metabolic pathways, neuronal function and inflammation play a significant role in
      the pathobiology of obesity and type 2 diabetes.

PMID- 18078526
TI  - Environmental conditions and Puumala virus transmission in Belgium.
AB  - BACKGROUND: Non-vector-borne zoonoses such as Puumala hantavirus (PUUV) can be
      transmitted directly, by physical contact between infected and susceptible hosts,
      or indirectly, with the environment as an intermediate. The objective of this
      study is to better understand the causal link between environmental features and
      PUUV prevalence in bank vole population in Belgium, and hence with transmission
      risk to humans. Our hypothesis was that environmental conditions controlling the
      direct and indirect transmission paths differ, such that the risk of transmission
      to humans is not only determined by host abundance. We explored the relationship
      between, on one hand, environmental variables and, on the other hand, host
      abundance, PUUV prevalence in the host, and human cases of nephropathia epidemica
      (NE). Statistical analyses were carried out on 17 field sites situated in Belgian
      broadleaf forests. RESULTS: Linear regressions showed that landscape attributes,
      particularly landscape configuration, influence the abundance of hosts in
      broadleaf forests. Based on logistic regressions, we show that PUUV prevalence
      among bank voles is more linked to variables favouring the survival of the virus
      in the environment, and thus the indirect transmission: low winter temperatures
      are strongly linked to prevalence among bank voles, and high soil moisture is
      linked to the number of NE cases among humans. The transmission risk to humans
      therefore depends on the efficiency of the indirect transmission path. Human risk
      behaviours, such as the propensity for people to go in forest areas that best
      support the virus, also influence the number of human cases. CONCLUSION: The
      transmission risk to humans of non-vector-borne zoonoses such as PUUV depends on
      a combination of various environmental factors. To understand the complex causal
      pathways between the environment and disease risk, one should distinguish between
      environmental factors related to the abundance of hosts such as land-surface
      attributes, landscape configuration, and climate - i.e., host ecology, - and
      environmental factors related to PUUV prevalence, mainly winter temperatures and
      soil moisture - i.e., virus ecology. Beyond a threshold abundance of hosts,
      environmental factors favouring the indirect transmission path (soil and climate)
      can better predict the number of NE cases among humans than factors influencing
      the abundance of hosts.

PMID- 18078525
TI  - Plasmid-based genetic modification of human bone marrow-derived stromal cells:
      analysis of cell survival and transgene expression after transplantation in rat
      spinal cord.
AB  - BACKGROUND: Bone marrow-derived stromal cells (MSC) are attractive targets for ex
      vivo cell and gene therapy. In this context, we investigated the feasibility of a
      plasmid-based strategy for genetic modification of human (h)MSC with enhanced
      green fluorescent protein (EGFP) and neurotrophin (NT)3. Three genetically
      modified hMSC lines (EGFP, NT3, NT3-EGFP) were established and used to study cell
      survival and transgene expression following transplantation in rat spinal cord.
      RESULTS: First, we demonstrate long-term survival of transplanted hMSC-EGFP cells
      in rat spinal cord under, but not without, appropriate immune suppression. Next,
      we examined the stability of EGFP or NT3 transgene expression following
      transplantation of hMSC-EGFP, hMSC-NT3 and hMSC-NT3-EGFP in rat spinal cord.
      While in vivo EGFP mRNA and protein expression by transplanted hMSC-EGFP cells
      was readily detectable at different time points post-transplantation, in vivo NT3
      mRNA expression by hMSC-NT3 cells and in vivo EGFP protein expression by hMSC-NT3
      EGFP cells was, respectively, undetectable or declined rapidly between day 1 and
      7 post-transplantation. Further investigation revealed that the observed in vivo
      decline of EGFP protein expression by hMSC-NT3-EGFP cells: (i) was associated
      with a decrease in transgenic NT3-EGFP mRNA expression as suggested following
      laser capture micro-dissection analysis of hMSC-NT3-EGFP cell transplants at day
      1 and day 7 post-transplantation, (ii) did not occur when hMSC-NT3-EGFP cells
      were transplanted subcutaneously, and (iii) was reversed upon re-establishment of
      hMSC-NT3-EGFP cell cultures at 2 weeks post-transplantation. Finally, because we
      observed a slowly progressing tumour growth following transplantation of all our
      hMSC cell transplants, we here demonstrate that omitting immune suppressive
      therapy is sufficient to prevent further tumour growth and to eradicate malignant
      xenogeneic cell transplants. CONCLUSION: In this study, we demonstrate that
      genetically modified hMSC lines can survive in healthy rat spinal cord over at
      least 3 weeks by using adequate immune suppression and can serve as vehicles for
      transgene expression. However, before genetically modified hMSC can potentially
      be used in a clinical setting to treat spinal cord injuries, more research on
      standardisation of hMSC culture and genetic modification needs to be done in
      order to prevent tumour formation and transgene silencing in vivo.

PMID- 18078527
TI  - Neuropsychology and clinical neuroscience of persistent post-concussive syndrome.
AB  - On the mild end of the acquired brain injury spectrum, the terms concussion and
      mild traumatic brain injury (mTBI) have been used interchangeably, where
      persistent post-concussive syndrome (PPCS) has been a label given when symptoms
      persist for more than three months post-concussion. Whereas a brief history of
      concussion research is overviewed, the focus of this review is on the current
      status of PPCS as a clinical entity from the perspective of recent advances in
      the biomechanical modeling of concussion in human and animal studies,
      particularly directed at a better understanding of the neuropathology associated
      with concussion. These studies implicate common regions of injury, including the
      upper brainstem, base of the frontal lobe, hypothalamic-pituitary axis, medial
      temporal lobe, fornix, and corpus callosum. Limitations of current
      neuropsychological techniques for the clinical assessment of memory and executive
      function are explored and recommendations for improved research designs offered,
      that may enhance the study of long-term neuropsychological sequelae of
      concussion.

PMID- 18078528
TI  - Inconsistency of performance on neglect subtype tests following acute right
      hemisphere stroke.
AB  - Hemispatial neglect has been conceptualized as having dissociable and potentially
      clinically relevant subtypes. However, the question of whether patient
      performance on neglect subtype measures is consistent over time remains largely
      unanswered. We examined changes in performance over time on measures of motor,
      perceptual, and personal neglect in 21 patients with neglect from acute right
      hemisphere stroke. Patients were assessed on three occasions, separated by at
      least one week, using a lateralized target test, lateralized response test, and
      modified fluff test. Across three testing timepoints, 18 (85.7%) patients changed
      subtype performance patterns at least once. In 13 (61.9%) of these patients,
      inconsistency between timepoints was not adequately accounted for by recovery. On
      initial testing, seven, patients (33.3%) demonstrated more than one neglect
      subtype symptom; by the third testing timepoint none of the patients demonstrated
      multiple symptoms. In the setting of acute stroke, performance on three measures
      of neglect symptoms is inconsistent across time. However, the distribution of
      neglect subtype symptoms appears to become more discrete over time. These
      findings complicate our understanding of the pathophysiology and potential
      prognostic value of neglect subtypes, and suggest that treatment decisions based
      on subtype performance assessed at a single timepoint, may be of limited utility.

PMID- 18078529
TI  - A demonstration of endogenous modulation of unilateral spatial neglect: the
      impact of apparent time-pressure on spatial bias.
AB  - Unilateral neglect, a lack of awareness for one side of space, is a common and
      debilitating consequence of stroke. Previous work has identified a relationship
      between enduring left neglect and diminished general alertness and shown that
      increasing alertness can temporarily reduce the severity of the spatial bias. In
      that research, alertness was modulated by loud tones or with pharmacological
      stimulants. Here we examine whether cognitive, endogenously driven changes can
      produce similar short-term improvements. Time-pressure is associated with
      increased subjective arousal and increased activation in cortical regions
      associated with alertness. Here five patients completed a spatial cancellation
      task with and without instructions regarding a time limit. Significant reductions
      in neglect severity were observed when patients believed that they were acting
      under time-pressure, despite the conditions being equivalent in the actual
      (unlimited) time available. Functional imaging work has highlighted the secondary
      effects that damage to networks mediating alertness can have on structurally
      intact spatial systems. The results here suggest that activation of presumably
      spared function in these damaged networks can induce moment-by-moment changes in
      spatial function and, crucially, that this can be achieved using entirely
      endogenous means.

PMID- 18078530
TI  - Intact emotion facilitation for nonsocial stimuli in autism: is amygdala
      impairment in autism specific for social information?
AB  - Atypical amygdala development may play a key role in the emergence of social
      disability and other symptoms of autism (Baron-Cohen et al., 2000; Schultz,
      2005). The mechanisms by which this may occur have received little attention,
      however, and most support from behavioral and imaging studies has been concerned
      with socially relevant stimuli such as faces. Given the complexity of amygdala
      function and its known role in many other emotional tasks, we examined whether
      individuals with autism would demonstrate impaired performance on several tasks
      that have been shown to require activation of the amygdala but that do not have
      any explicit social meaning. Relative to a typical comparison group matched for
      age and IQ, our sample of 37 adolescents and adults with autism (mean age=19.7
      years) demonstrated equivalent facilitation for perception and learning of
      emotionally relevant stimuli. On each of four tasks, there were significant main
      effects of emotion condition on performance for both groups. Future research
      regarding atypical amygdala function and emotion processing in autism should
      consider whether the response to nonsocial emotion factors (including negative
      valence or high arousal) may be intact, despite difficulties in responding to
      socially relevant stimuli.

PMID- 18078531
TI  - Executive function, mentalizing and humor in major depression.
AB  - Major depression is associated with cognitive deficits including memory,
      executive functions, and affect perception, which have been linked to dysfunction
      of fronto-subcortical networks. However, little is known about social cognition
      on more complex socially relevant tasks, such as humor processing. In this
      investigation a computerized humor-processing task was administered to 27
      patients with a diagnosis of major depression (Dep) and 27 healthy controls (HC).
      Theory of mind (mentalizing) and executive functions were also assessed. Both
      groups were similar in IQ, age, and gender. Depressed patients performed below
      the control group with respect to both affective and cognitive aspects of humor
      processing, and these were related to mentalizing and executive performance. Our
      findings suggest social cognition deficits in major depression. Ability to
      process humor and appreciate mentalistic perspectives may in turn influence
      social interactions and should be given consideration in therapeutic approaches
      to depression.

PMID- 18078532
TI  - Depressive rumination reduces specificity of autobiographical memory recall in
      acquired brain injury.
AB  - Individuals with acquired brain injuries (ABI) often experience depression
      following injury, with estimated rates between 20 and 40% within the first year
      and up to 50% thereafter (Fleminger et al., 2003). Previous studies with non
      brain-injured individuals have identified that rumination is prevalent in both
      the development and maintenance of depression. The study aimed to explore how
      depressive rumination may contribute to overgeneral memory recall in ABI
      patients, by assessing the effects of manipulating ruminative self-focus on
      autobiographical memory performance across levels of brain injury. Fifty-eight
      ABI individuals with mild (28) to moderate/severe (30) cognitive impairments were
      assessed on measures of mood, rumination and autobiographical memory. They were
      then randomly assigned into matched groups for an intervention (a distraction) or
      a rumination task. Following intervention, they were re-assessed for
      autobiographical recall and rumination. Findings indicate that ruminative self
      focus reduced specificity of autobiographical memory in individuals with ABI,
      suggesting that depressive rumination plays a role in the reduced access to
      autobiographical memories. Higher baseline levels of depression and rumination
      were also associated with less specificity in recall. These findings indicate the
      value of identifying and treating depression among this population.

PMID- 18078533
TI  - Detecting the significance of changes in performance on the Stroop Color-Word
      Test, Rey's Verbal Learning Test, and the Letter Digit Substitution Test: the
      regression-based change approach.
AB  - Serial neuropsychological assessment is often conducted to monitor changes in the
      cognitive abilities of individuals over time. Because practice effects occur and
      the reliability of test scores is less than perfect, it is difficult to judge
      whether varying test results should be attributed to chance trends or to real
      changes in underlying cognitive abilities. In a large sample of adults (age
      range, 49-81 years), we evaluated the influence of age, gender, and education on
      test-retest changes in performance after 3 years on Rey's Verbal Learning Test
      (VLT), the Stroop Color-Word Test (SCWT), and the Letter Digit Substitution Test
      (LDST). A new statistical method was applied to assess the significance of
      changes in test performance (i.e., the regression-based change method). The
      results showed that test-retest changes differed as a function of age for the VLT
      Total recall 1-3, VLT Total recall 1-5, VLT Delayed recall, and LDST measures. An
      age x gender interaction was found for the SCWT Interference change score,
      suggesting that the age-related decline in executive functioning after 3 years
      was more pronounced for males than for females. A normative change table with
      appropriate corrections for the relevant independent variables was established.

PMID- 18078534
TI  - Mental rotation of congenitally absent hands.
AB  - We compared motor imagery performance of normally limbed individuals with that of
      individuals with one or both hands missing since birth (i.e., hand amelia). To
      this aim, 14 unilaterally and 2 bilaterally amelic participants performed a task
      requiring the classification of hands depicted in different degrees of rotation
      as either a left or a right hand. On the same task, 24 normally limbed
      participants recapitulated previously reported effects; that is, that the hand
      motor dominance and, more generally, a lifelong use of hands are important
      determinants of left-right decisions. Unilaterally amelic participants responded
      slower to hands corresponding to their absent, compared with their existing,
      hand. Moreover, left and right hand amelic participants showed prolonged reaction
      times to hands (whether left or right) depicted in unnatural orientations
      compared with natural orientations. Among the bilateral amelics, the individual
      with phantom sensations, but not the one without, showed similar differentiation.
      These findings demonstrate that the visual recognition of a hand never physically
      developed is prolonged, but still modulated by different rotation angles. They
      are further compatible with the view that phantom limbs in hand amelia may
      constrain motor imagery as much as do amputation phantoms.

PMID- 18078535
TI  - Executive functioning in preschool children born very preterm: relationship with
      early white matter pathology.
AB  - Despite evidence for executive dysfunction in school-aged preterm children, less
      is known about the early development of these difficulties or their underlying
      neuropathology. This study used prospective longitudinal data from a regional
      cohort of 88 very preterm and 98 full-term comparison children to examine the
      executive functioning (EF) of preschool children born very preterm. The
      relationship between the severity of neonatal cerebral white matter (WM)
      abnormalities on magnetic resonance imaging (MRI) at term equivalent and
      children's EF at ages two and four years (corrected age) was examined. At age
      four, very preterm children with WM abnormalities performed less well than full
      term children on the Detour Reaching Box, a measure of behavioral inhibition and
      cognitive flexibility, even after controlling for child IQ, SES, and medical
      background. Examination of patterns of EF performance between the ages of 2 and 4
      years showed that the performance of all groups improved with age. However, very
      preterm children with mild and moderate-severe WM abnormalities were
      characterized by higher rates of consistent performance impairments. These
      findings support the presence of early and persistent executive difficulties in
      preschool children born very preterm, and highlight the importance of white
      matter pathology in the development of executive impairments.

PMID- 18078536
TI  - Vertical scanning biases and their possible influence on reading direction:
      celtic wisdom or folly?
AB  - The reason people read from top to bottom is unknown, but could be related to
      brain-mediated directional biases or environmental factors. To learn if there is
      a brain-mediated directional bias responsible for top-down reading direction, we
      evaluated the directional scanning in the vertical dimension by using directional
      letter and face cancellation tasks. Twenty participants were instructed to cancel
      either target letters or faces using either an up-down or down-up direction, with
      the stimuli located in left, right, and center hemispace. The results indicated
      significant differences in completion time between the search direction (up vs.
      down) and spatial position for the letter cancellation task, with a faster
      completion time for the bottom-up scan in right space and top-down in left space.
      Because the left hemisphere primarily attends to contralateral right hemispace
      our results suggest that, when attending to letter stimuli, the left hemisphere
      is biased to scan in a proximal to distal (upward) direction. Although the
      reasons why this is reversed in left hemispace and why we did not see directional
      biases in the face condition remains unclear, these results do suggest that the
      direction in which we learn to read is inconsistent with the brain's intrinsic
      directional bias.

PMID- 18078537
TI  - Long-term effects of risperidone versus haloperidol on verbal memory, attention,
      and symptomatology in schizophrenia.
AB  - There is evidence in the literature that cognitive functions in schizophrenia
      (SC) may be improved by atypical neuroleptics (NLPs) in contrast to typical
      medication, but there is still controversy regarding this apparent superiority of
      atypical drugs. In this study, we assessed the differential effects of
      risperidone and haloperidol on verbal memory, attention, and psychiatric symptoms
      in SC. The performance of 28 SC participants, randomly assigned to risperidone (2
      6 mg/day) or haloperidol (2-40 mg/day), was compared with that of healthy
      controls. The California Verbal Learning Test (CVLT), the d2 Cancellation Test,
      and the Positive and Negative Symptoms Scale were administered at baseline and 3,
      6, and 12 months. Relative to controls, all SC participants showed markedly
      impaired verbal memory and processing speed at each assessment period. There was
      no differential effect between the two NLPs on CVLT and d2 performance. However,
      risperidone was more effective than haloperidol in reducing psychiatric symptoms.
      Improvement in symptom severity was not associated with improvement in
      neurocognitive performance on these specific tests. Neither conventional nor
      atypical neuroleptic medications improved neurocognitive functioning over a 12
      month follow-up, suggesting that psychopathological improvement under risperidone
      is independent of cognitive function.

PMID- 18078538
TI  - Differences in executive functioning in children with heavy prenatal alcohol
      exposure or attention-deficit/hyperactivity disorder.
AB  - Children with either fetal alcohol spectrum disorder (FASD) or attention
      deficit/hyperactivity disorder (ADHD) display deficits in attention and executive
      function (EF) and differential diagnosis of these two clinical groups may be
      difficult, especially when information about prenatal alcohol exposure is
      unavailable. The current study compared EF performance of three groups: children
      with heavy prenatal alcohol exposure (ALC); nonexposed children with attention
      deficit/hyperactivity disorder (ADHD); and typically developing controls (CON).
      Both clinical groups met diagnostic criteria for ADHD. The EF tasks used were the
      Wisconsin Card Sorting Test (WCST), the Controlled Oral Word Association Test
      (COWAT), and the Trail Making Test (TMT). Results indicated different patterns of
      deficit; both clinical groups displayed deficits on the WCST and a relative
      weakness on letter versus category fluency. Only the ALC group displayed overall
      deficits on letter fluency and a relative weakness on TMT-B versus TMT-A. In
      addition, WCST performance was significantly lower than expected based on IQ in
      the ADHD group and significantly higher than expected in the ALC group. These
      results, which indicate that, although EF deficits occurred in both clinical
      groups, the degree and pattern of deficit differed between the ALC and ADHD
      groups, may improve differential diagnosis.

PMID- 18078540
TI  - Verbal (animal) fluency scores in age/grade appropriate minority children from
      low socioeconomic backgrounds.
AB  - Two hundred-thirteen children in grades 1 through 8 were asked to rapidly
      generate as many names of animals as they could in 60 seconds. These children
      were age appropriate for their grade level in school, did not receive any form of
      special education services, and as a group showed (estimated) average
      intellectual ability. They were primarily from minority (particularly Hispanic)
      backgrounds and came from families with low socioeconomic status. Normative data
      are presented. Hierarchical multiple regression analysis revealed that the age
      range/grade level score accounted for 21.5% of the variability in fluency scores
      and the Vocabulary level of the child accounted for an additional 5.7%. Level of
      performance on this animal fluency task was not lower than what has been reported
      in primarily white children from middle socioeconomic backgrounds.

PMID- 18078539
TI  - Neuropsychological strategies for detecting early dementia.
AB  - As new and more effective treatments for Alzheimer's disease (AD) emerge, the
      development of efficient screening strategies in educationally and racially
      diverse primary care settings has increased in importance. A set of candidate
      screening tests and an independent diagnostic assessment were administered to a
      sample of 318 patients treated at a geriatric primary care center. Fifty-six
      subjects met criteria for dementia. Exploratory analysis led to the development
      of three two-stage screening strategies that differed in the composition of the
      first stage or Rapid Dementia Screen, which is applied to all patients over the
      age of 65. The second stage, applied to those patients who screen positively for
      dementia, is accomplished with the Free and Cued Selective Reminding Test to
      detect memory impairment. Using clinical diagnosis as a gold standard, the
      strategies had high sensitivity and specificity for identifying dementia and
      performed better for identifying AD than non-AD dementias. Sensitivity and
      specificity did not differ by race or education. The strategies provide an
      efficient approach to screening for early dementia.

PMID- 18078541
TI  - Semantic memory as assessed by the Pyramids and Palm Trees Test: the impact of
      sociodemographic factors in a Spanish-speaking population.
AB  - The objective of this study is to obtain preliminary normative data on the
      performance the Pyramids and Palm Trees Test (PPT) for a Spanish-speaking
      population. The effects of age, gender, and educational level on the PPT test
      were also analyzed. A total of 234 healthy participants, with a broad range of
      age (18-80 years) and education (1-20 years) performed the three-picture version
      of the PPT. The mean performance was 51.1 out of 52 possible points (SD=1.3). PPT
      performance did not vary with age or gender. However, subjects with less than 6
      years of formal education scored significantly lower than those with more than 6
      years of education though this effect was confounded with age because the group
      with lower education was also older. Given the ceiling effects of the PPT,
      further investigation is needed to determine if the visual PPT is sensitive to
      mild semantic memory impairment.

PMID- 18078542
TI  - Paging equals functionality.

PMID- 18078543
TI  - Long-term compensatory treatment of organizational deficits in a patient with
      bilateral frontal lobe damage.
AB  - Evans et al. (1998) described compensatory strategy use in R.P., a patient with
      executive dysfunction following bilateral frontal lobe damage who had difficulty
      acting upon her intentions. A pager was used to remind R.P. of regularly
      scheduled activities, along with a checklist that aimed to moderate a
      perseverative routine. Although successful, 10 years after the original
      intervention, the strategies were no longer used, and considerable everyday
      problems were evident. In the current study, we conducted a follow-up assessment
      to examine potential reasons for this deterioration. No change in
      neuropsychological functioning was evident. Whereas the previous study introduced
      the two strategies together, and examined effects upon separate goals, in the
      current study we reintroduced the two strategies separately, and examined effects
      on three common goals. In addition to prompting specific activities, we aimed to
      support completion of more general goals (those that could be enacted within a
      wider window of time). The paging intervention had a dramatic effect on all three
      measured behaviors, at a much more consistent level than the checklist. We
      suggest that, in addition to direct reminders, the pager can cue a process of
      goal monitoring that bridges the gap between intention and action.

PMID- 18078544
TI  - A comparison of letter and digit processing in letter-by-letter reading.
AB  - The extent to which letter-by-letter reading results from a specific orthographic
      deficit, as compared with a nonspecific disturbance in basic visuoperceptual
      mechanisms, is unclear. The current study directly compared processing of letters
      and digits in a letter-by-letter reader, G.M., using a rapid serial visual
      presentation (RSVP) task and a speeded matching task. Comparisons were made to a
      group of six brain-damaged individuals without reading deficits. In the RSVP
      task, G.M. had increased difficulty reporting the target identities when they
      were letters, as compared with digits. Although this general pattern was also
      evident in the control group, the magnitude of the letter-digit accuracy
      difference was greater in G.M. Similarly, in the matching task, G.M. was slower
      to match letters than digits, relative to the control group, although his
      response times to both item types were increased. These data suggest that letter
      by-letter reading, at least in this case, results from a visuoperceptual encoding
      deficit that particularly affects letters, but also extends to processing of
      digits to a lesser extent. Results are consistent with the notion that a left
      occipitotemporal area is specialized for letter processing with greater
      bilaterality in the visual processing of digits.

PMID- 18078545
TI  - X-ray solution scattering (SAXS) combined with crystallography and computation:
      defining accurate macromolecular structures, conformations and assemblies in
      solution.
AB  - Crystallography supplies unparalleled detail on structural information critical
      for mechanistic analyses; however, it is restricted to describing low energy
      conformations of macromolecules within crystal lattices. Small angle X-ray
      scattering (SAXS) offers complementary information about macromolecular folding,
      unfolding, aggregation, extended conformations, flexibly linked domains, shape,
      conformation, and assembly state in solution, albeit at the lower resolution
      range of about 50 A to 10 A resolution, but without the size limitations inherent
      in NMR and electron microscopy studies. Together these techniques can allow multi
      scale modeling to create complete and accurate images of macromolecules for
      modeling allosteric mechanisms, supramolecular complexes, and dynamic molecular
      machines acting in diverse processes ranging from eukaryotic DNA replication,
      recombination and repair to microbial membrane secretion and assembly systems.
      This review addresses both theoretical and practical concepts, concerns and
      considerations for using these techniques in conjunction with computational
      methods to productively combine solution scattering data with high-resolution
      structures. Detailed aspects of SAXS experimental results are considered with a
      focus on data interpretation tools suitable to model protein and nucleic acid
      macromolecular structures, including membrane protein, RNA, DNA, and protein
      nucleic acid complexes. The methods discussed provide the basis to examine
      molecular interactions in solution and to study macromolecular flexibility and
      conformational changes that have become increasingly relevant for accurate
      understanding, simulation, and prediction of mechanisms in structural cell
      biology and nanotechnology.

PMID- 18078546
TI  - The future of telemedicine--take the organizational challenge!
AB  - Implementation of telemedicine has not been as rapid as was expected in the
      1990s. Diffusion of technologies can be complex and is known to be influenced by
      many factors. Organizational problems are crucial for the future of telemedicine,
      but have been gravely underestimated. When a telemedicine service is established
      we have a virtual organization. Internal organizational consequences of
      telemedicine are very common and more effective use of the technology is likely
      to require organizational changes. For different applications of the technology
      there are similarities, and differences, in internal organizational consequences.
      Organizational matters connected with telemedicine are dealt with in a new book,
      The Organizational Challenge for Health Care from Telemedicine and E-health, the
      full text of which is available via the Internet. In the book, solutions are
      outlined for common organizational problems in telemedicine. Managers must
      actively lead organizational changes. Replacing simplified optimism with realism
      may be very important for the future of telemedicine.

PMID- 18078547
TI  - Adoption of telemedicine in Scottish remote and rural general practices: a
      qualitative study.
AB  - We conducted a qualitative interview study to explore the factors that have
      facilitated and prevented the adoption of telemedicine in general practice in
      remote and rural Scotland. Face-to-face interviews were carried out with general
      practitioners (GPs) and practice nurses in 26 of Scotland's most remote practices
      and five of the seven most rural health boards. The interview study found that
      GPs were more positive about the use of computers and telemedicine than nurses.
      Although electronic access to simple data, such as laboratory results, had become
      widely accepted, most respondents had very little experience of more
      sophisticated telemedicine applications, such as videoconferencing. There was
      widespread scepticism about the potential usefulness of clinical applications of
      telemedicine, although it was perceived to have potential benefit in facilitating
      access to educational resources. A number of barriers to the adoption of
      telemedicine were reported, including concerns that videoconferencing could
      diminish the quality of communication in educational and clinical settings, and
      that telemedicine would not fit easily with the organizational routines of the
      practices. Policy-makers should prioritize strategies to develop educational
      programmes, as these are more likely to succeed than clinical initiatives. It may
      then follow that clinicians will see opportunities for use in their clinical
      work.

PMID- 18078548
TI  - A novel use of photo messaging in the assessment of nasal fractures.
AB  - We evaluated a new method of assessing patients referred to the otolaryngology
      department with nasal injury. Patients possessing a mobile phone with built-in
      camera took an image of their face and sent it to the department for assessment.
      A decision was then made as to whether the patient needed further consultation or
      treatment. This method of nasal fracture assessment might avoid unnecessary
      referrals to the department. A prospective single blinded study was carried out.
      Twenty-five patients with a nasal injury took photographs of their face using a
      mobile phone camera. These images were reviewed and assessment made about whether
      a nasal fracture was present. The patient was then clinically assessed, the
      clinical examination being the 'gold standard' method of assessment. There was
      little agreement between photographic and clinical assessment. Sixty-two percent
      of patients who were clinically assessed to have a nasal fracture requiring
      manipulation were not picked up on assessment of their image. The greatest
      agreement with clinical assessment was the patient's own opinion as to whether
      there was new deviation of their nasal bone.

PMID- 18078549
TI  - Wireless live streaming video of surgical operations: an evaluation of
      communication quality.
AB  - We evaluated a mobile video system for surgical teleconsultation. A video
      streaming server in the operating room transmitted video and audio to a hand-held
      computer (personal digital assistant [PDA]) over a wireless local area network.
      Two groups of 20 surgeons (each with 12 qualified surgeons and eight surgeons
      between the 2nd and the 4th year of training) participated in the tests. For
      voice transmission, correct understanding of numbers was achieved in 100% of the
      cases (n = 1000) and 98% of medical terms (n = 400). The quality of the video
      displayed on the PDA was assessed by the recognition of different operating room
      scenarios. Only 62% (SD 17) of the structures were identified clearly on the hand
      held device (n = 400). The accuracy improved to 78% (SD 15) (n = 400) if the same
      scenario was observed on a larger (50 cm) video screen (p < 0.001). Accuracy was
      significantly better if audio conversation was possible. The quality evaluation
      by the consultants showed that the PDA display size and quality were sufficient
      for clinical use.

PMID- 18078550
TI  - A survey of patients attending an eye clinic in Ghana.
AB  - To determine the motivation behind patients attending hospital eye services, 30
      in-depth interviews were conducted in Accra, Ghana, using a semi-structured
      format. Patients were interviewed from five different populations. Discomfort in
      the eye was the main reason for attending the eye clinic. Patients had high
      expectations of the doctors and expected to be cured. Limitations such as money,
      time and travel restricted the frequency of visits. Patients were not generally
      against doctors seeking second opinions although some expressed disappointment at
      their doctor being unable to make an immediate diagnosis. The majority of
      patients were happy for the doctor to seek a second opinion via teleconsultation
      or any other method. Care needs to be taken to ensure patients return for the
      outcome of these opinions.

PMID- 18078551
TI  - Remote measurement via the Internet of upper limb range of motion in people who
      have had a stroke.
AB  - An Internet-based goniometer has recently been developed which can be used for
      the remote quantification of joint range of motion (ROM). We evaluated the
      validity and intra- and inter-rater reliability of this goniometer for the
      measurement of upper limb ROM in 10 people who had had a stroke. The movements on
      which the device was evaluated were shoulder flexion, shoulder abduction, elbow
      flexion, wrist flexion, wrist extension, forearm supination and forearm
      pronation. Measurements performed using the Internet-based goniometer were
      compared with measurements made using the most widely accepted clinical joint ROM
      measurement tool, the universal goniometer. The Internet-based goniometer was
      found to be a valid tool for the measurement of upper limb ROM, with the
      disagreement between the two measurement tools ranging from 1.1-2.4 degrees . The
      Internet-based goniometer was also shown to possess a high level of intra- and
      inter-rater reliability (all intra class correlation coefficients>0.93). The
      results suggest that therapists can confidently use the Internet-based goniometer
      to measure the upper limb ROM in people who have had a stroke.

PMID- 18078552
TI  - Providing basic hearing tests using remote computing technology.
AB  - We administered pure tone and otoacoustic emissions testing to subjects in a
      distant community using remote computing technology. Fifteen men and 15 women
      ranging in age from 18-30 years were tested. An audiometer was used to measure
      subject pure tone thresholds. In addition, distortion product otoacoustic
      emissions (DPOAEs) data were recorded using a portable system. Both systems were
      interfaced to a PC which was connected to the local area network at Minot State
      University (MSU). An examiner at Utah State University, 1100 km away, could
      control both the DPOAE and the audiometer equipment at MSU. Overall, the pure
      tone means for the face-to-face and telemedicine trials were equivalent at each
      frequency. Moreover, DPOAE recordings exhibited equivalent results at each
      frequency for telemedicine and face-to-face trials. These results support the use
      of remote computing as a telemedicine method for providing pure tone audiometry
      and DPOAE testing to distant communities.

PMID- 18078553
TI  - Improvements in health by consultations using mobile videophones among
      participants in a community health promotion programme.
AB  - We conducted a health promotion programme using mobile videophones and examined
      changes in the participants' health conditions, health practices and their
      subjective sense of health. The subjects were volunteers (mean age, 59 years)
      recruited from a community-based health promotion group. A focus group interview
      was conducted to evaluate the quality of the programme. All subjects expressed
      concerns about lifestyle-related diseases. The subjects participated in group
      activities at least twice a month under the supervision of public health
      professionals. Six of them participated in mobile care in addition to group
      activities (mobile care group) and the other eight subjects (control group)
      participated in the regular group activities. Three consecutive health
      examinations were carried out at intervals of 12 weeks. There were significant
      reductions in low-density lipoprotein cholesterol (P = 0.01) and health locus of
      control internal score (P = 0.05) in the mobile care group. The subjects who used
      mobile phones were highly accepting of the use of the device for further health
      consultations. There is potential for wider application of mobile videophones in
      health promotion programmes for people who have concerns about lifestyle-related
      diseases and are seeking healthier lifestyles.

PMID- 18078554
TI  - Mobile phone short message service messaging for behaviour modification in a
      community-based weight control programme in Korea.
AB  - We conducted a community-based anti-obesity programme using mobile phone short
      message service (SMS) messaging. A total of 927 participants were recruited and
      visited a public health centre for initial assessment. Mobile phones were used to
      deliver short messages about diet, exercise and behaviour modification once a
      week. After a 12-week anti-obesity programme they visited the public health
      centre again. Four hundred and thirty-three subjects (47%) successfully completed
      their weight control programme. There were mean reductions of weight, waist
      circumference and body mass index of 1.6 kg (P < 0.001), 4.3 cm (P < 0.001) and
      0.6 kg/m(2) (P < 0.001), respectively. Over two-thirds of the subjects had a
      reduction in waist circumference of 5-7.5 cm. A post-intervention survey showed
      that the majority of participants were satisfied with the weekly SMS messages and
      information brochures delivered by post. SMS messaging may be an effective method
      of behaviour modification in weight control and anti-obesity health education
      programmes when promoted by community health centres.

PMID- 18078555
TI  - Mobile phone consultation for community health care in rural north India.
AB  - We conducted a study to ascertain the acceptability and feasibility of
      consultation by mobile phone in a rural area of northern India. The mobile phone
      number of a community physician was advertised to the general public and people
      were invited to telephone at any time for a medical consultation. Details of the
      calls received were recorded. During a seven-month study, 660 calls were
      received. The mean call duration was 2.7 min. Eighty percent of calls were made
      by men. Forty-eight percent of calls were made during office hours. A total of
      417 (63%) calls were for seeking advice, 146 (22%) were for outpatient follow-up,
      23 (4%) were for seeking appointments and the remaining 74 (11%) for other
      reasons. The most common problems were skin, respiratory, mental health and
      sexual problems. Of the 387 callers who were interviewed at follow-up, 302 (78%)
      stated that they had followed the advice provided. Of these, 91% found the advice
      very helpful in managing their health problems. About 96% of users wished to
      continue to use the service in future. The majority of calls made were of a
      primary care nature which could easily be dealt with by phone. The concept of
      using mobile phones for medical consultation seemed to be acceptable to people in
      rural Haryana.

PMID- 18078556
TI  - Challenges of telehealth research in clinical settings.

PMID- 18078558
TI  - Screening: a step too far. A matter of concern.

PMID- 18078559
TI  - Computed tomography screening: safe and effective?

PMID- 18078560
TI  - Is NESTROFT sufficient for mass screening for beta-thalassaemia trait?
AB  - OBJECTIVES: Prevention of beta-thalassaemia trait will, for the foreseeable
      future, hinge on effective screening strategies. Routine use of haematological
      data from automated cell counters may complement the results of the Naked Eye
      Single Tube Red cell Osmotic Fragility Test (NESTROFT), especially because of the
      high cost of a false-negative error. Our objective was to assess the potential
      additive value of routine haematological data in screening for beta-thalassaemia
      trait. SETTINGS: Community survey of asymptomatic volunteers. METHODS: Using the
      NESTROFT results, haematological data and haemoglobin A(2) concentration from
      1435 young, asymptomatic Sindhi subjects recruited in a population-based survey,
      and statistical analysis by classification tree approach, we examined whether
      haematological parameters have discriminatory utility additional to that of
      NESTROFT in screening for beta-thalassaemia trait. RESULTS: We observed that in
      the derivation subset from which the classification tree was generated, there was
      only a marginal--albeit statistically significant--improvement in the screening
      performance of NESTROFT, whereas there was no such improvement attributable to
      the use of haematological parameters in a separate validation subset. CONCLUSION:
      Our results further substantiate the claim that the use of NESTROFT is highly
      indicated for screening for beta-thalassaemia trait in regions where the
      prevalence is high and the resources are constrained.

PMID- 18078561
TI  - Sensitivity in cancer screening.
AB  - OBJECTIVE: We propose three concepts of sensitivity in cancer screening and apply
      to data on prostate cancer. Conceptual entities: Sensitivity is the indicator on
      the ability of screening to find cancer in the detectable preclinical phase
      (DPCP). The ability is usually specified as to the screening test. We call this
      entity the test sensitivity. Test positivity with histological confirmation
      refers to the full diagnostic process and we call the corresponding entity as
      episode sensitivity. Ultimately, a screening programme identifies a proportion of
      cancers in the DPCP in the total target population, that we call programme
      sensitivity. We derive the formulae for these three sensitivities consistent with
      the incidence method. EXAMPLE: Our example on estimation of the three
      sensitivities is from a randomized screening trial for prostate cancer in
      Finland. The estimates by incidence method were substantially different, 85% for
      test sensitivity, 48% for episode sensitivity and 36% for programme sensitivity.
      CONCLUSION: More than one concept of sensitivity with standard method of
      estimation is needed to describe the ability of screening to identify the disease
      in the DPCP.

PMID- 18078562
TI  - Surrogate endpoints for cancer screening trials: general principles and an
      illustration using the UK Flexible Sigmoidoscopy Screening Trial.
AB  - Cancer screening is aimed primarily at reducing deaths. Thus, site-specific
      cancer mortality is the appropriate endpoint for evaluating screening
      interventions. However, it is also the most demanding endpoint, requiring follow
      up and a large numbers of patients order to have adequate power. Therefore, it is
      highly desirable to have surrogate endpoints that can reliably predict mortality
      reductions many years earlier. We here review a range of surrogate markers in
      terms of their potential advantages and pitfalls, and argue that a measure which
      weights incident cancers according to their predicted mortality has many
      advantages over other measures and should be used more routinely. Application to
      the UK Flexible Sigmoidoscopy Screening Trial data suggests that predicted
      colorectal cancer mortality, based on stage-specific incidence, is a more
      powerful endpoint than actual mortality and could advance the analysis time by
      about three years. Total colorectal cancer incidence as a surrogate endpoint
      provides little advance in the analysis time over actual mortality. The approach
      requires reliable prognostic data, (e.g. stage), for both the study cohort and a
      representative sample of the whole population. The routine collection of such
      data should be a priority for cancer registries. Surrogate endpoints should not
      replace a long-term analysis based directly on mortality, but can provide
      reliable early indicators which can be useful both for monitoring ongoing
      screening programmes and for making policy decisions.

PMID- 18078563
TI  - Factors associated with referral compliance of abnormal immunochemical faecal
      occult blood test.
AB  - OBJECTIVE: This study investigated factors associated with the referral
      compliance of positive immunochemical faecal occult blood test (iFOBT). SETTING:
      Data were from a subset of people who received iFOBT at Taipei county of Taiwan
      in 2005. METHODS: All subjects with positive iFOBT were referred to hospital for
      further diagnostic examinations. In total, 226 such subjects who did not accept
      referral within 60 days were identified as the non-compliant group from the
      record of Public Health Bureau. Frequency-matched 219 subjects were sampled from
      the 599 people who accepted referral within 60 days as the compliant group.
      Telephone interviews were performed according to questionnaire designed basically
      under the Health Belief Model. Multiple logistic regression was used to assess
      effects of possible associated factors for referral compliance. RESULTS: A total
      of 145 persons in the compliant group and 115 persons in the non-compliant group
      completed the interview. Factors including 'perceived susceptibility' and 'cue to
      action: information' were positively associated with, while 'casual personality'
      was negatively associated with referral compliance. CONCLUSIONS: Three factors in
      Health Belief Model were associated with referral compliance after positive FOBT.

PMID- 18078564
TI  - Cost-effectiveness analysis for determining optimal cut-off of immunochemical
      faecal occult blood test for population-based colorectal cancer screening (KCIS
      16).
AB  - OBJECTIVES: We aimed to determine the optimal cut-off of the immunochemical
      faecal occult blood test (iFOBT) by using cost-effectiveness analysis. METHODS: A
      total of 22,672 subjects aged 50 years or older were invited to have an uptake of
      iFOBT. We collected data from screen-detected cases for the cut-off above 100
      ng/mL and obtained interval cancers from a nationwide cancer registry for a cut
      off below 100 ng/mL. We found a total of 65 colorectal cancer (CRC) cases,
      including 43 detected by screen and 22 diagnosed between screens (interval
      cases). The optimal cut-off was first determined by receiver operating
      characteristics (ROC) curve analysis. Formal economic evaluation was further
      applied to identifying the optimal cut-off by assessing the minimum incremental
      cost-effectiveness ratio (ICER), an indicator for cost per life year gained
      (effectiveness), given a series of cut-offs of iFOBT, ranging from 30 to 200
      ng/mL compared with no screening. RESULTS: ROC curve analysis found the optimal
      cut-off of iFOBT to be 100 ng/mL at which the sensitivity, false-positive and
      odds of being affected given a positive result were 81.5% (70.2%-89.2%), 5.7%
      (5.4%-6.0%) and 1.24 (1.19-1.32), respectively. The area under ROC curve was 0.87
      (0.81-0.93). In economic appraisal, the screening programme irrespective of any
      cut-off dominated (less cost and more effectiveness) over the control group. The
      optimal cut-off (the lowest ICER) was 110 ng/mL at which an average of 0.054 life
      year was gained and that of 950 ($US) was saved. CONCLUSIONS: We used cost
      effectiveness to identify 110 ng/mL as the optimal cut-off of iFOBT in a
      Taiwanese population-based screening for CRC. Our model provides a useful
      approach for health policy-makers in designing population-based screening for CRC
      to determine the optimal cut-off of iFOBT when cost and effectiveness need to be
      taken into account.

PMID- 18078565
TI  - Results from the UK NHS Breast Screening Programme 2000-05.
AB  - OBJECTIVE: To present results from the UK NHS breast screening programme (NHSBSP)
      for the six-year period from 1 April 1999 to 31 March 2005, and to compare these
      with targets. METHODS: Data are collected annually from all UK screening units on
      standard KC62 return forms. RESULTS: The prevalence of screen-positive cancer
      (cancer detection rate) has increased at both rounds during the six-year period.
      At the incident round, cancer detection rates increased by 24%, from 5.4 per 1000
      in 2000 to 6.7 per 1000 in 2005 and the detection of small cancers (< or = 10 mm)
      has increased by 40%. Generally, quality measures in the programme continue to
      improve. However, while rates of recall at the incident screen decreased from
      3.8% in 2000 to 3.6% in 2005, at the prevalent round, in 2005, 22% of units
      continued to recall more than 10% of women to assessment. CONCLUSIONS: The
      results suggest that the performance of the programme continues to improve. In
      the future, analysis of data on interval cancers will assist the interpretation
      of cancer detection rates.

PMID- 18078566
TI  - Scheduling mammography screening for the early detection of breast cancer in
      Korean women.
AB  - OBJECTIVE: To propose an efficient screening schedule for breast cancer among
      Korean women using the stochastic model in which the age-specific incidence rate
      was considered. SETTING: Female breast cancer data in the Korea Central Cancer
      Registry 2002. METHODS: The stochastic model was based on the threshold method,
      in which the schedule is determined by a pre-specified threshold value. The
      threshold value was defined as the probability of being in a preclinical state of
      breast cancer at age 40 years. The sensitivity of the mammography was specified
      as 0.7. Two models for mean sojourn time (MST) in the preclinical state were
      considered; MSTs for Model I were 2 (ages < 50 years), 3 (ages 50-59 years), and
      4 years (ages > or = 60 years), and MSTs for Model II were 3, 4, and 5 years for
      the corresponding age groups. RESULTS: The threshold method for Model I generated
      19 examinations within the screening ages of 40-69 years. Each screening time was
      determined at ages 40.0, 41.6, 43.2, 44.8, 46.0, 47.2, 48.4, 49.6, 50.7, 51.7,
      52.7, 53.7, 54.7, 56.2, 57.8, 59.4, 61.3, 63.1, and 64.9 years. The schedule
      sensitivity of Model I was 64.2%, which was higher than that (57.5%) of the
      biennial periodic schedule. Model II included 11 screenings between the ages of
      40 and 69 years and also showed a higher schedule sensitivity, especially for
      women aged 40 years as compared with the biennial screening. CONCLUSIONS: This
      finding suggests that the threshold screening schedule for breast cancer increase
      the schedule sensitivity by reflecting the age-specific incidence rate of a
      population.

PMID- 18078567
TI  - Basal phenotype: a powerful prognostic factor in small screen-detected invasive
      breast cancer with long-term follow-up.
AB  - OBJECTIVE: To assess the frequency and prognostic significance of a basal
      phenotype in a group of women with screen-detected invasive breast cancers with
      long-term follow-up and to focus particularly on women with small ( < 15 mm)
      breast cancers. METHODS: The study group was derived by finding women common to a
      consecutive series of 1944 invasive breast cancers diagnosed in Nottingham
      between 1986 and 1998 with a known basal phenotype status and a prospectively
      collected database of all screen-detected breast cancers. In total, 356 women
      constituted the study group. Pathological and radiological features were
      recorded. Basal cell markers used were CK5/6 (cloneD5/16134) and CK14 (clone
      LL002). Tumours were classified as of basal phenotype if > or = 10% staining was
      seen with either marker. RESULTS: Of all screen-detected lesions, 43 (12%) had a
      basal immunophenotype and 313 (88%) were non-basal. There were 15 (35%) and 40
      (13%) breast cancer deaths in the basal group and nonbasal groups, respectively (
      P = 0.0006). On univariate analysis, nodal stage, histological grade, lympho
      vascular invasion (LVI) status, invasive size and basal phenotype had prognostic
      significance. On multivariate analysis, basal phenotype, LVI and nodal stage
      maintain prognostic significance. Of the 189 women with < 15 mm lesions, eight of
      20 (40%) of the basal group and eight of 169 (5%) of the non-basal group died of
      breast cancer ( P < 0.0001). On multivariate analysis, basal phenotype was the
      only factor to maintain independent prognostic significance. CONCLUSIONS: Basal
      phenotype is a powerful prognostic factor for women with small screen-detected
      invasive breast cancer.

PMID- 18078570
TI  - Programmed automation of modulator cold jet flow for comprehensive two
      dimensional gas chromatographic analysis of vacuum gas oils.
AB  - A method is described for automating the regulation of cold jet flow of a
      comprehensive two-dimensional gas chromatograph (GCxGC) configured with flame
      ionization detection. This new capability enables the routine automated
      separation, identification, and quantitation of hydrocarbon types in petroleum
      fractions extending into the vacuum gas oil (VGO) range (IBP-540 degrees C).
      Chromatographic data acquisition software is programmed to precisely change the
      rate of flow from the cold jet of a nitrogen cooled loop modulator of a GCxGC
      instrument during sample analysis. This provides for the proper modulation of
      sample compounds across a wider boiling range. The boiling point distribution of
      the GCxGC separation is shown to be consistent with high temperature simulated
      distillation results indicating recovery of higher boiling semi-volatile VGO
      sample components. GCxGC configured with time-of-flight mass spectrometry is used
      to determine the molecular identity of individual sample components and
      boundaries of different molecular types.

PMID- 18078571
TI  - Towards comprehensive hydrocarbons analysis of middle distillates by LC-GCxGC.
AB  - The detailed characterization of middle distillates is essential for a better
      understanding of reactions involved in refining processes. Owing to a higher
      resolution power and an enhanced sensitivity, but especially to a group-type
      ordering in the chromatographic plane, comprehensive two-dimensional gas
      chromatography (GCxGC) offers unsurpassed characterization possibilities for
      petroleum samples. However, GCxGC fails to totally discriminate naphthenes from
      unsaturates occurring in hydrotreated diesel samples. This article aims at
      promoting the implementation of LC-GCxGC for the quantitative determination of
      hydrocarbon distribution in middle distillates, including naphthenes. In this
      configuration, liquid chromatography (LC) enables the separation of hydrocarbons
      into two fractions (viz., saturated and unsaturated) before the subsequent
      analysis of each fraction by GCxGC. In this paper, the choice of GCxGC conditions
      in order to achieve the separation and identification of hydrocarbons by chemical
      class is discussed; under these conditions, naphthenes are separated according to
      the number of saturated rings. For the first time, the presence of di-, tri-, and
      tetra-naphthenes resulting from the hydroconversion of aromatics can clearly be
      evidenced. A quantitative procedure for the determination of the distribution of
      hydrocarbons, including the distribution of naphthenes according to the number of
      saturated rings, is also proposed and discussed in detail. LC-GCxGC is found to
      provide an unequalled degree of information that will widely contribute to a
      better understanding of hydroconversion processes.

PMID- 18078572
TI  - Analysis of biodiesel/petroleum diesel blends with comprehensive two-dimensional
      gas chromatography.
AB  - Comprehensive two-dimensional gas chromatography (GCxGC) is used to analyze
      petroleum diesel, biodiesel, and biodiesel/petroleum diesel blends. The GCxGC
      instrument is assembled from a conventional gas chromatograph fitted with a
      simple, in-line fluidic modulator. A 5% phenyl polydimethylsiloxane primary
      column is coupled to a polyethylene glycol secondary column. This column
      combination generates chromatograms where the fatty acid methyl esters (FAMEs)
      found in biodiesel occupy a region that is also populated by numerous cyclic
      alkanes and monoaromatics found in petroleum. Fortunately, the intensities of the
      petroleum hydrocarbon peaks are far lower than the intensities of the FAME peaks,
      even for blends with low biodiesel content. This allows the FAMEs to be
      accurately quantitated by direct integration. The method is calibrated by
      analyzing standard mixtures of soybean biodiesel in petroleum diesel with
      concentrations ranging from 1 to 20% v/v. The resulting calibration curve
      displays excellent linearity. This curve is used to determine the concentration
      of a B20 biodiesel/petroleum diesel blend obtained from a local retailer.
      Excellent precision and accuracy are obtained.

PMID- 18078573
TI  - A comprehensive two-dimensional gas chromatography method for analyzing
      extractable petroleum hydrocarbons in water and soil.
AB  - A flow-switching two-dimensional gas chromatography (GCxGC) apparatus has been
      constructed that can operate at temperatures as high as 340 degrees C. This
      system is employed to analyze complex hydrocarbon mixtures such as diesel fuel,
      gas-oil, motor oil, and petroleum contaminated environmental samples. The GCxGC
      system generates two-dimensional chromatograms with minimal overlap between the
      aliphatic and aromatic regions This allows these compound classes to be
      independently quantitated without prior fractionation. The GCxGC system is used
      to analyze extracts of spiked water samples, wastewater, and soil. The accuracy
      of the method is compared to that of the Massachusetts Extractable Petroleum
      Hydrocarbons (MA EPH) method. The GCxGC system generates a quantitative accuracy
      similar to the MA EPH method for the analysis of spiked water samples. The GCxGC
      method and the MA EPH method generate comparable levels of total hydrocarbons
      when wastewater is analyzed, but the GCxGC method detects a significantly higher
      aromatic content and lower aliphatic content. Both the GCxGC method and MA EPH
      method measure comparable levels of aromatics in the soil samples.

PMID- 18078574
TI  - Capillary flow technology with multi-dimensional gas chromatography for trace
      analysis of oxygenated compounds in complex hydrocarbon matrices.
AB  - By employing multi-dimension gas chromatography with capillary flow technology in
      combination with highly selective capillary columns and a pressurized liquid
      injection system, light oxygenated compounds such as methanol, ethanol, n
      propanol, 2-propanol, and n-butanol in the presence of either light hydrocarbon,
      heavy hydrocarbon, or aromatic matrices can be measured accurately with minimal
      possibility of a false positive. Using this technique, a detection limit of at
      least 0.20 ppm (w/w) with a linear correlation coefficient greater than 0.9993
      over a range from 0.5 ppm to 600 ppm (w/w) and a relative standard deviation of
      greater than 2.7% are achieved for the solutes tested. The technique can also be
      effective for the measurement of other classes of oxygenated compounds such as
      ethers, aldehydes, and ketones. Another added benefit for the implementation of
      capillary flow technology is the capability to conduct column back-flushing,
      where heavier, undesired solutes in a sample can be back-flushed from the
      chromatographic system to improve system cleanliness and sample throughput.

PMID- 18078575
TI  - A unified approach for the measurement of individual or total volatile organic
      sulfur compounds in hydrocarbon matrices by dual-plasma chemiluminescence
      detector and low thermal mass gas chromatography.
AB  - A novel gas chromatographic technique has been developed, offering dual
      analytical capability of either speciation or rapid measurement of total volatile
      sulfur compounds in hydrocarbon matrices using the same hardware. The technique
      employs a pressurized liquid injection system for the delivery of volatile liquid
      hydrocarbons, low thermal mass gas chromatography, and a dual-plasma sulfur
      chemiluminescence detector to enable this dual capability with a high degree of
      sensitivity and selectivity towards sulfur-containing compounds. Using the
      technique described, a detection limit in the range of 20 ppb sulfur and less
      than 30 s analysis is attained. Response is linear over five orders of magnitude,
      with a high degree of repeatability.

PMID- 18078576
TI  - Application of ICP-MS as a multi-element detector for sulfur and metal hydride
      impurities in hydrocarbon matrices.
AB  - Maturation of inductively coupled plasma-mass spectrometry (ICP-MS) in terms of
      size, reliability, and cost has had a significant impact on its consideration as
      a viable detector for gas chromatography. Its generally excellent sensitivity for
      those elements it can measure has been a contributing factor. A method for sulfur
      speciation in various hydrocarbon products is investigated, as well as sulfur and
      metal hydride contaminants in high purity hydrocarbon feed stocks. Detection
      limits for sulfur species in hydrocarbon liquids and gases are approximately 5
      and 10 ppb, respectively, as sulfur. Lower detection limits on the order of 100
      parts per trillion are achieved for arsine. The use of collision cell technology
      (CCT) is exploited to remove interferences. CCT has been described elsewhere (1)
      using helium or helium-hydrogen mixtures for suppression of (16)O(16)O(+)
      interference with (32)S. In this work, a novel approach is investigated which
      uses oxygen to remove this interference by shifting it in a comprehensive
      fashion. The advantage of operating the system at full power with a tandem gas
      and liquid interface is also discussed.

PMID- 18078577
TI  - Physical and chemical characterization of petroleum products by GC-MS.
AB  - There is a need for reliable and fast means of monitoring refining, conversion,
      and upgrading processes aiming to increase the yield of light distillates, and
      thus, reducing the oil barrel bottoms. By simultaneously utilizing the FID and
      mass selective detectors while splitting the column effluent in a controlled way,
      it is possible to obtain identical gas chromatograms and total ion chromatograms
      from a single run. This means that besides the intensity vs. time graphs, the
      intensity vs. mass and boiling point can also be obtained. As a result, physical
      and chemical characterization can be performed in a simple and rapid manner.
      Experimental results on middle, heavy distillates, and crude oil fractions show
      clearly the effect of upgrading processes on the chemical composition and yields
      of diesel, jet fuels, and high vacuum gasoil fractions. The methodology is fully
      compliant with ASTM D-2887, D-7213, D-6352, and D7169 for simulated distillation
      and the previously mentioned mass spectrometry standards. The group type analysis
      correlated satisfactorily with high-performance liquid chromatography data.

PMID- 18078578
TI  - Determination of total biodiesel fatty acid methyl, ethyl esters, and hydrocarbon
      types in diesel fuels by supercritical fluid chromatography-flame ionization
      detection.
AB  - A method for determining total biodiesel methyl and ethyl ester content in diesel
      fuels by supercritical fluid chromatography-flame ionization detection (SFC-FID)
      is developed. A silica column typically used for determining aromatics in
      conventional diesel fuels by ASTM D5186 is back-flushed after separation of the
      hydrocarbons to allow elution of the various esters as a single "total biodiesel"
      distinct peak. The modification concurrently allows the determination of total
      aromatic hydrocarbons and their distribution as mono- and polynuclear compounds,
      as described in the current version of D5186. The instrument response is linear
      from 1.0% to 50% biodiesel esters with a signal-to-noise ratio of 25 at the 0.1%
      level. The short-term relative standard is 0.8%. Normalized percent quantitation
      using a hydrocarbon response factor of 1.00 and an ester response factor of 1.19
      provide an average percentage error of 1.8% when measuring actual
      biodiesel/hydrocarbon fuel blends. The ester response factor is the average of
      the response factors of 10 pure ester compounds. These responses are calculated
      from respective solutions of each ester and the four compounds, hexadecane,
      toluene, tetralin, and naphthalene, as used for the D5186 response factor
      mixture.

PMID- 18078579
TI  - A LC-electrospray tandem MS method for the analysis of naltrexone in canine
      plasma employing a molecular model to demonstrate the absence of internal
      standard deuterium isotope effects.
AB  - A simple and sensitive method is described for the determination of naltrexone
      (NAL), an opioid antagonist, in dog plasma. Sample processing involved a single
      step liquid-liquid extraction, followed by evaporation of the supernatant, and
      reconstitution of the residue prior to injection into the liquid chromatograph.
      The peak height ratio of NAL to [15,15,16-(2)H] naltrexone (NAL-d(3)) was used
      for quantitation. Observation of the chromatograms for NAL and NAL-d(3) revealed
      that the mean retention times of the compounds were 1.32 and 1.31 min,
      respectively. The almost identical retention times possibly accounted for the
      absence of matrix effects influencing quantitation. Molecular mechanics
      calculations using SYBYL software were carried out to qualitatively and
      quantitatively assess analyte and isotopic internal standard stationary phase
      interactions. Binding energy values of -10.22 and -10.26 kcal/mole were obtained
      for NAL and NAL-d(3), respectively. These data predict, semi-quantitatively, the
      absence of deuterium isotope effects that may influence quantitation. Calibration
      curves were linear from 10 pg/mL to 5014 pg/mL with a weighting factor of 1/x.
      Precision and accuracy and reverse predicted concentration residuals were within
      15%. The method has been used successfully for the analysis of plasma samples
      from a pilot subcutaneous implantation study in dog.

PMID- 18078580
TI  - Optimization of a high-performance liquid chromatography method for the
      separation and identification of six different classes of phenolics.
AB  - Flavonoids are chemical moieties widely distributed in certain plants that are
      important biologically active constituents of a daily human diet, with
      significant pharmacological potential (anti-hepatotoxic, anti-allergic, anti
      inflammatory, anti-osteoporotic, and anti-tumor activities). Thus keeping in view
      the importance of this class of compounds, a rapid method for the separation and
      identification of fifteen phenols belonging to six different types of phenolics
      in a sole analysis has been developed and validated using selectivity, precision,
      recovery, and robustness as parameters. The method developed, which is rapid,
      accurate, and robust for the analysis of different classes of phenols, can be
      used in the quality control and standardization of plant extracts as well as
      herbal drugs, including compound herbal formulations.

PMID- 18078581
TI  - Development and validation of a TLC-densitometric method for the simultaneous
      quantitation of strychnine and brucine from Strychnos spp. and its formulations.
AB  - A simple, sensitive, and specific thin-layer chromatography densitometric method
      has been developed for the simultaneous quantitation of strychnine and brucine.
      These two marker compounds are quantitated in the seeds of Strychnos nux-vomica,
      Strychnos ignatii, and its formulations. The method involves densitometric
      evaluation of strychnine and brucine after resolving it by high-performance TLC
      on silica gel plate with toluene-ethyl acetate-diethyl amine-methanol (7:2:1:0.3
      v/v) as the mobile phase. The method is validated for precision (interday and
      intraday), repeatability, and accuracy. The relationship between the
      concentration of standard solutions and the peak response is linear within the
      concentration range of 160 to 480 ng/spot for strychnine and 80 to 480 ng/spot
      for brucine. Instrumental precision is found to be 0.54 and 0.78 (% CV), and
      repeatability of the method is 1.01 and 1.06 (% CV) for strychnine and brucine,
      respectively. Accuracy of the method is checked by recovery study conducted at
      three different levels and the average percentage recovery is found to be 99.13%
      for strychnine and 100.16% for brucine. The proposed HPTLC method for the
      simultaneous quantitation of strychnine and brucine is found to be simple,
      precise, specific, sensitive, and accurate, and it can be used for routine
      quality control of raw material of Strychnos spp. It also can be applied in
      quantitating any of these marker compounds in other formulations.

PMID- 18078582
TI  - Thiophilic interaction chromatography of mammalian and avian transferrins.
AB  - Transferrins are a class of iron-binding proteins widely distributed in
      biological fluids. All transferrins possess two metal binding sites, each of
      which can bind a ferric iron. Transferrins play a major role in plasma iron
      transport and have anti-bacterial, anti-inflammatory, and immunological
      functions. Lactoferrin is an iron-binding bilobal protein of the transferrin
      family found in neutrophilic leukocytes and external secretion of mammals. In an
      earlier communication, we have shown that both human serum transferrin and
      lactoferrin bind to 3S-gel. Ovotransferrin, the major egg-white protein, is an
      avian transferrin. In this paper, the details of the binding of mammalian and
      avian transferrins to 2S gel is presented. Both, apo and holo ovotransferrin,
      bind to 2S T-gel. Holo and apo lactoferrin from other mammalian species such as
      cow, rabbit, dog, mouse, and rat bind to T-gel.

PMID- 18078583
TI  - Frequent HTLV-1 infection in the offspring of Peruvian women with HTLV-1
      associated myelopathy/tropical spastic paraparesis or strongyloidiasis.
AB  - OBJECTIVES: To describe the frequency of HTLV-1 infection among offspring of
      mothers who had presented with HTLV-1-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP), strongyloidiasis, or asymptomatic HTLV-1 infection, and to
      identify factors associated with HTLV-1 infection. METHODS: In a descriptive
      study, records were reviewed of HTLV-1-positive women and their offspring who had
      been tested for HTLV infection at a public hospital in Lima, Peru, from 1989 to
      2003. Sons and daughters of women who had presented with strongyloidiasis,
      HAM/TSP, or asymptomatic infection were eligible for this study. RESULTS: Three
      hundred seventy subjects were included: 279 were the offspring of 104 mothers
      presenting with HAM/TSP, 58 were the offspring of 22 mothers with
      strongyloidiasis, and 33 were the offspring of 26 asymptomatic mothers. Mean age
      of the offspring at the time of testing was 26 years (standard deviation 12).
      Nineteen percent of the offspring tested positive for HTLV-1: 6% (2/33) of those
      with asymptomatic mothers, 19% (52/279) among the offspring of mothers with
      HAM/TSP, and 31% (18/58) among the offspring of mothers presenting with
      strongyloidiasis On multiple logistic regression analysis, three factors were
      significantly associated with HTLV-1: (a) duration of breast-feeding (odds ratio
      [OR] = 15.1; [4.2-54.1] for 12 to 24 months versus less than 6 months breast
      feeding); (b) clinical condition of the mother (OR = 8.3 [1.0-65.3] for HAM/TSP
      and OR = 11.5 [1.4-98.4] for strongyloidiasis in comparison with offspring of
      asymptomatic mothers); and (c) transfusion history (OR = 5.5 [2.0-15.2]).
      CONCLUSIONS: In addition to known risk factors for HTLV-1 transmission (duration
      of breast-feeding and history of blood transfusion), maternal HAM/TSP and
      strongyloidiasis were associated with seropositivity among offspring of HTLV-1
      infected mothers.

PMID- 18078584
TI  - [Suicide trends in Colombia, 1985-2002].
AB  - OBJECTIVES: To report trends in mortality from suicide in Colombia from 1985 to
      2002 by sex, age group, and method, and determine the number of Years of
      Potential Life Lost (YPLL) to suicide during this period. METHODS: Age- and sex
      specific and age-adjusted crude mortality rates were calculated based on
      mortality and population information available from the official database of the
      Department of National Statistics Administration, Colombia. YPLL were estimated
      and adjusted for societal impact, age, and poor quality of mortality records. The
      results were tabulated according to codes X600-X849 and Y870 from the
      International Statistical Classification of Disease and Related Health Problems,
      10th revision (ICD-10), and codes E950-E959 from the 9th revision (ICD-9).
      RESULTS: Suicide rates have been climbing in Colombia since 1998, particularly
      among young adults and males. The highest rates among males were in the age
      groups 20-29 years of age and over 70 years of age, and rates increased over
      time. Among females, the highest rates were recorded for the group 10-19 years of
      age. The YPLL rose in proportion with the increase in suicides, from 0.81% in
      1981 to 2.20% in 2002. Among males, the most common methods used were firearms
      and explosives, hanging, and poison, with a relative increase in hanging; whereas
      among females, poison was most common. CONCLUSIONS: A rising trend in suicide
      rates in Colombia was confirmed, especially among the productive segment of the
      population, which has resulted in a marked increase in YPLL.

PMID- 18078585
TI  - The increase of diabetes mortality burden among Brazilian adults.
AB  - OBJECTIVE: To estimate diabetes-related deaths among Brazilian adults between
      1999 and 2003 and to investigate demographic factors associated with reporting
      diabetes as an associated cause of death. METHODS: All deaths with diabetes as
      the underlying or associated cause were identified using the Brazilian Mortality
      Data System. Analysis was performed by sex, age, year, state of residence, and
      place of death. Mortality rates were age standardized by the 2000 Brazilian
      population. FINDINGS: A total of 237 946 deaths (8.8%) were related to diabetes;
      in 4.2% of deaths it was the underlying cause and in 4.6% it was an associated
      cause. Between 1999 and 2003, age-standardized mortality rates for diabetes as
      the underlying cause increased 14% among males and 9% among females, while
      mortality with diabetes as an associated cause increased 22% and 28%,
      respectively. Diabetes appeared more often as an associated cause in death
      certificates among older individuals and in those residing in Sao Paulo State; it
      appeared less often as an associated cause among women, brown- and black-skinned
      populations, and in deaths occurring outside hospitals. Cardiovascular diseases
      accounted for 54.5% of the underlying causes of death when diabetes was an
      associated cause. CONCLUSION: Diabetes was related to almost 9% of the deaths in
      the South and Southeast regions of Brazil. Mortality from diabetes is increasing,
      especially deaths with diabetes as an associated cause. The probability of having
      diabetes as the underlying cause of death is greater among women and nonwhite
      individuals. Our results reinforce the importance of using multiple causes of
      death to monitor diabetes, because half the individuals with the disease will die
      of another cause, especially cardiovascular diseases.

PMID- 18078586
TI  - [Sociocultural factors and physical activity level in early adolescence].
AB  - OBJECTIVE: To describe the level of physical activity in adolescents born in 1993
      in the city of Pelotas, Brazil, and to evaluate the effect of sociocultural
      variables on those levels. METHODS: A combined ethno-epidemiological methodology
      was employed. In the epidemiological study, 4 452 adolescents born in 1993 were
      interviewed. Physical activity level was evaluated by means of a questionnaire.
      Adolescents with fewer than 300 minutes of physical activity per week were
      classified as sedentary. The ethnographic study included 69 adolescents randomly
      selected from among all cohort participants. On average, three in-depth
      interviews were carried out (about one every 6 months), with mothers and
      adolescents being interviewed separately. RESULTS: The prevalence of a sedentary
      lifestyle was 48.7% (95%CI: 46.5 to 50.8) in boys and 67.5% (95%CI: 65.6 to 69.5)
      in girls (P < 0.001). The independent variable presenting the strongest
      association with physical activity level was the weekly frequency with which the
      adolescent met friends outside of school. The ethnographic study showed that boys
      have more social and family support to engage in physical activities in
      adolescence, but that many parents associate poor school performance with the
      amount of time spent outside the home. CONCLUSIONS: This study suggests that
      physical activity is often viewed as competing with family values in adolescence.
      This perspective should be explored in future studies and discussed with families
      so that physical activity may be adopted as a cultural norm.

PMID- 18078587
TI  - Injury in the Americas: the relative burden and challenge.
AB  - OBJECTIVES: To present evidence to support a higher priority for injury
      prevention in initiatives, research, and budget allocations. METHODS: Recent data
      (2000) for deaths from injury, infectious disease, heart disease, and cancer from
      11 countries in the Region of the Americas were analyzed. Analyses focused on:
      first, Potentially Productive Years of Life Lost (PPYLL, discounted) from deaths
      occurring from 0-64 years of age; second, Years of Potential Life Lost (YPLL)
      from 1-64 years; and third, Years Lived with Disability (YLD). The burdens of
      injury and infectious disease were compared to the Pan American Health
      Organization (PAHO) budget allocations for these areas. RESULTS: There is a clear
      cut disparity between funds allocated and the magnitude of injury burden as
      compared to the burden of infectious disease. CONCLUSIONS: In making decisions on
      budgetary allocations, the Member States of PAHO must consider the potential
      impact of injury research and control on the health of their populations.

PMID- 18078588
TI  - [Nutritional status of the poor, marginalized adults of the Triqui ethnic group
      in Oaxaca, Mexico].
AB  - OBJECTIVES: To further understanding of the nutritional transition process by
      studying possible changes over time in the nutritional status of the Triqui
      ethnic group in the state of Oaxaca, Mexico. METHODS: A retrospective study was
      conducted using anthropometric data available from three prior studies (end of
      the 19th century, 1940, and 2002). Means and z scores for height, weight, and
      body mass index of Triqui adults were calculated using Frisancho reference data.
      Statistical analyses of the results were performed with Student's t and chi
      square tests. Sociocultural information was collected through interviews and
      direct observations, as well as from the available literature. RESULTS: The
      height of Triqui adults has remained very low. A majority of Triqui women were
      found to be short or very short; this, coupled with the low level of education
      and high rates of illiteracy and monolingualism, is indicative of a culture that
      does not favor females. The appearance of overweight and obesity among the men
      studied in 2002, relative to those studied in 1940, is cause for concern.
      Overweight was also recorded among the women in 2002. CONCLUSIONS: Despite the
      limitations shared by all retrospective studies, these results confirm that the
      nutritional status of the Triquis is different now from what it was 60 years ago
      and that these changes are related to the cultural changes the group is
      experiencing. To further understand this epidemiologic phenomenon, where
      malnutrition and obesity coexist, cross-disciplinary studies are needed to
      analyze the biological, social, and cultural factors involved, so that culturally
      appropriate measures can be adopted.

PMID- 18078589
TI  - Evaluating the costs of pneumococcal disease in selected Latin American
      countries.
AB  - OBJECTIVES: To estimate the costs of pneumococcal disease in Brazil, Chile and
      Uruguay, to describe how these costs vary between different patient groups, and
      to discuss factors that affect these cost variations. METHODS: The cost of
      pneumococcal disease was estimated from the health care perspective. For each
      country, baseline cost estimates were primarily developed using health resources
      information from patient-level data and facility-specific cost data. A regression
      model was constructed separately for four types of pneumococcal diseases. The
      skewness-kurtosis test and the Cook-Weisberg test were performed to test the
      normality of the residuals and the heteroscedasticity, respectively. RESULTS: The
      treatment of pneumococcal meningitis generated up to US$ 5 435 per child. The
      treatment costs of pneumococcal pneumonia were lower, ranging from US$ 372 per
      child to US$ 3 483 per child. Treatment of acute otitis media cost between US$ 20
      per child and US$ 217 per child. The main source of treatment costs variations
      was level of service provided and country in which costs were incurred. However,
      the tendency of costs to change with these variables was not statistically
      significant at the 5% level for most pneumococcal disease models. CONCLUSIONS:
      Pneumococcal disease resulted in significant economic burden to selected health
      care systems in Latin America. The patterns of treatment cost of pneumococcal
      disease showed a great deal of variation.

PMID- 18078590
TI  - [Individual and contextual determinants of the prevalence of untreated caries in
      Brazil].
AB  - OBJECTIVE: To describe the prevalence of untreated caries among adolescents in
      Brazil and to analyze the association between caries and individual and
      contextual factors in the municipalities where these adolescents live. METHODS: A
      Ministry of Health database (projeto SB-Brasil) provided health records on 16 833
      adolescents from 15-19 years of age. The study variable used was the presence of
      at least one permanent tooth having been lost to caries. The individual variables
      considered were: sex, ethnic group, living in an urban versus a rural area, and
      being a student or not. Contextual variables related to the municipality were:
      municipal human development index (MHDI), proportion of households connected to
      the water system, and water fluoridation for 5 years or more. Multilevel logistic
      regression analysis was carried out to adjust the outcome to the individual and
      contextual variables. RESULTS: Individual determinants related to a higher
      probability of untreated caries were: the ethnic group described as "black or
      brown," (adjusted odds ratio, OR(adjust) = 1.79; 1.68 to 1.92); and living in a
      rural area (OR(adjust) = 1.31; 1.19 to 1.45). Being a student was identified as a
      protective factor (OR(adjust) = 0.67; 0.62 to 0.73). Secondary variables
      identified as contextual determinants of caries were MHDI (adjusted coefficient
      beta = -0.213), water fluoridation (beta = -0.201), and households connected to
      the water system (beta = -0.197). CONCLUSIONS: The results show inequalities in
      the distribution of health services in the various Brazilian regions, and suggest
      that inequalities may also be present in the effectiveness of the services
      provided. Policies to increase access to fluoride-treated water and school
      enrollment may contribute to preventing caries in adolescents.

PMID- 18078591
TI  - [On the innovation of primary care in Americas].

PMID- 18078593
TI  - Philanthropic prize to remember that Latin American children's health is a
      priority.

PMID- 18078594
TI  - Time-dependent changes in distribution of basic fibroblast growth factor
      immunoreactive cells in rat hippocampus after status epilepticus.
AB  - OBJECTIVE: In this study, we aimed to examine time-dependent morphologic changes
      and quantitative alterations in the density of basic fibroblast growth factor
      (bFGF)-immunoreactive (ir) astrocytes and CA2 pyramidal neurons in dorsal
      hippocampus of rats after status epilepticus (SE) induced by kainic acid (KA)
      injection. METHODS: Wistar albino rats were injected with saline or KA i.p. to
      investigate time-dependent alterations in morphology and the number of bFGF-ir
      astrocytes and neurons in the dorsal hippocampus 15, 30 and 90 days after KA
      injection. RESULTS: Fifteen days after KA injection, gliosis was present
      throughout the hippocampus and neuronal loss was evident in CA1 and CA3 regions,
      which was more severe after 30 and 90 days. KA-injected rats demonstrated
      significantly increased number of both bFGF-ir astrocytes throughout the
      hippocampus and pyramidal neurons in CA2 after 15 days and decreased number after
      30 and 90 days. CONCLUSION: The decrease in the number of bFGF-ir astroglia and
      neurons in long term after KA injection may indicate a decrease in the production
      of bFGF and/or number of bFGF-ir cells, suggesting that protective effects of
      bFGF might be altered during epileptogenesis in the hippocampus.

PMID- 18078595
TI  - Giant thrombosed fusiform aneurysm at the basilar trunk successfully treated with
      endovascular coil occlusion following bypass surgery: a case report and review of
      the literature.
AB  - OBJECTIVE: Giant fusiform aneurysms at the basilar trunk tend to have a poor
      natural history, and the surgical management for these aneurysms remains
      controversial. For these aneurysms, basilar trunk occlusion may offer a
      potentially long-lasting cure. However, the strategy for these aneurysms is
      difficult when the collateral supply from the carotid circulation is poor. The
      authors herein present a successful case of a thrombosed giant fusiform aneurysm
      at the basilar trunk with a poor collateral supply using repeated balloon test
      occlusion (BTO) and a second bypass surgery. CASE REPORT: A 46-year-old female
      was admitted to our institute because of progressing double vision. A radiologic
      examination revealed a thrombosed giant fusiform aneurysm at the upper basilar
      trunk, and the collateral supply from carotid circulation was poor. We attempted
      to perform a second bypass surgery before the basilar trunk coil occlusion due to
      intolerance after the repeated BTO. After confirmation of her tolerance against
      the third BTO, the aneurysm was successfully trapped using the endovascular
      technique. CONCLUSION: Various kind of bypass surgery should be tried for
      endovascular trapping of giant fusiform basilar trunk aneurysms, and repeated BTO
      is necessary to confirm the tolerance after bypass surgery especially for the
      complex aneurysms without a sufficient collateral supply.

PMID- 18078596
TI  - [Frequency of antibodies anti-Ehrlichia canis, Borrelia burgdorferi and
      Dirofilaria immitis antigens in dogs from microrregion Ilheus-Itabuna, State of
      Bahia, Brazil].
AB  - In order to detect the positivity to antigens of Dirofilaria immitis, antibodies
      anti-Borrelia burgdorferi and anti-Ehrlichia canis, 200 canine blood samples were
      collected as followed: 100 from the municipality of Ilheus and 100 from Itabuna,
      State of Bahia. The kit Snap 3DX (IDEXX Laboratories) was used to performe
      serology. None of the tested animalswere positive for antigens of D. immitis.
      Only two dogs of them were positive for antibodies anti-B. burgdorferi. From all
      the samples analyzed, 72 (36%) were positive for antibodies anti-E. canis, 43
      from Ilheus and 29 from Itabuna (p=0.027).

PMID- 18078597
TI  - [Metazoan parasites of six fishes species from Lajes Reservoir in the State of
      Rio de Janeiro, Brazil].
AB  - From April 2002 to July 2003, 231 freshwater fishes from Lajes Reservoir in the
      State of Rio de Janeiro, Brazil (22 degrees 42' - 22 degrees 50'S, 43 degrees 53'
      - 44 degrees 05'W) were necropsied to study their community metazoan parasites:
      39 Astyanax bimaculatus (Linnaeus, 1758), 79 A. fasciatus (Cuvier, 1819), 23
      Hypostomus affinis (Steindachner, 1877), 26 Hoplias malabaricus (Bloch, 1794), 30
      Loricariichthys castaneus (Castelnau, 1855) and 34 Trachelyopterus striatulus
      (Steindachner, 1876). The majority of specimens of H. affinis (95.6%) and H.
      malabaricus (84.6%) was parasitized by one or more metazoan species. In A.
      bimaculatus, A. fasciatus, L. castaneus and T. striatulus 41%, 39.2%, 56.7 and
      14.7% of specimens were parasitized, respectively. Eight different metazoan
      parasites species were collected: 2 in A. bimaculatus, 3 in A. fasciatus, 3 in H.
      affinis, 4 in H. malabaricus, 4 in L. castaneus and 1 in T. striatulus. The
      parasites of the six host species showed the typical aggregated pattern of
      distribution. Two cases of negative correlation between host's total length and
      prevalence and parasite abundance were detected. The parasite community of L.
      castaneus showed the higher values of mean intensity, index of dispersion and
      higher values of diversity. The parasite communities of the studied fishes showed
      scarcity of significant correlations of parasitic abundance, species richness and
      diversity with the size of the host. The low species richness and diversity of
      parasite communities could be originated by the oligotrophic characteristics of
      the Lajes Reservoir.

PMID- 18078598
TI  - [External morphology of the adults specimens of Paratanaisia bragai (Santos,
      1934)(Diginea: Eucotylidae)].
AB  - Adult specimens of Paratanaisia bragai collected from renal ducts of Columba
      livia naturally infected, were fixed in glutaraldehyde 2.5 degrees and processed
      for scanning electron microscopy. Two distinct types of scales had been
      identified, bifid and simple scales, disposed in transversal rows, on the
      tegument of dorsal and ventral face of the body. Also show in details the oral
      sucker subterminal, well developed and acetabulum of size reduced, located in
      third medium of the body, surrounded for small protuberance and four papillae on
      its edge.

PMID- 18078599
TI  - Prevalence of anti-Neospora caninum antibodies in cattle from the state of Mato
      Grosso do Sul, Brazil.
AB  - Neospora caninum is an obligate intracellular parasite that can infect domestic
      and wild canids, as well as ruminants and equines. It was described in 1988 and
      has been known as a major cause of abortion in bovines and neuromuscular
      alterations and death in dogs. To estimate the prevalence of bovine neosporosis
      in the 22 municipalities of the so-called Estrato 1 subregion of the Brazilian
      state of Mato Grosso do Sul, blood samples were collected from cows aged 24
      months and older, from December 2003 to March 2004. During sample collection, a
      questionnaire was used to gather data of epidemiological interest. The samples
      were subjected to serological diagnosis (indirect fluorescence antibody test -
      IFAT). Prevalences of 14.9% (449/2488) and 69.8% (143/205) were found for the
      animals and herds sampled, respectively. The variable found to be associated with
      seropositivity to N. caninum was abortion (OR 2.52; CI 1.25-5.06). The results
      revealed the presence of infection by N. caninum in the herds investigated,
      drawing attention to its role as a potential cause of abortion in cattle in Mato
      Grosso do Sul.

PMID- 18078600
TI  - Morphology and morphometry of three Plasmodium juxtanucleare (Apicomplexa:
      Plasmodiidae) isolates.
AB  - In this work, three isolates of Plasmodium juxtanucleare have been analyzed based
      on morphological, morphometric and parasitic parameters. Each isolate was sampled
      from naturally infected adult chicken (Gallus gallus) from rural areas of three
      Brazilian municipalities: Seropedica (22 degrees 48' S; 43 degrees 41' W), in the
      state of Rio de Janeiro; Cruzeiro (22 degrees 33' S; 44 degrees 57' W), in the
      state of Sao Paulo; and Santa Barbara do Tugurio (21 degrees 15' S; 43 degrees
      27' W), in the state of Minas Gerais. The blood samples taken from each infected
      chicken were inoculated in three groups of ten young chicken (21 days old). Blood
      smears of the experimentally infected chicken were sampled every two days until
      the 69th day in order to evaluate the parasitemia. For the morphological
      descriptive and morphometric analyses, we measured 30 individuals from each of
      the intraerythocytic states, measures of the major (MD) and minor diameters (md),
      the estimation of morphometric index (Mi=md/MD) and size (T=pab, a=md/2; b=MD/2).
      The results indicated low and homogeneous parasitemia rates in the three strains,
      which showed differences among shape and size of the parasitic stadia displayed.

PMID- 18078601
TI  - Insecticide susceptibility of horn flies, Haematobia irritans (Diptera:
      Muscidae), in the State of Mato Grosso do Sul, Brazil.
AB  - Horn fly susceptibility to insecticides was evaluated in the state of Mato Grosso
      do Sul, Brazil, from October 2000 to September 2002. Insecticide bioassays (n=57)
      were conducted in 38 ranches from 14 municipalities throughout the state. Horn
      flies from wild populations were collected on cattle and exposed to filter papers
      impregnated with cypermethrin, permethrin, or diazinon and mortality was assessed
      after two hours. Resistance to cypermethrin was detected in all populations, with
      resistance ratios (RR) ranging from 27.6 to 91.3-fold. Permethrin bioassays
      provided apparently low levels of resistance (RR<5), however, resistant flies
      were found in 96.9% of the populations based on diagnostic concentrations. From
      both pyrethroid bioassays, resistance was detected in 97.4% of the populations.
      On the other hand, a high susceptibility to diazinon (RR< or =1.1) was detected
      in all populations. Pyrethroid products, most cypermethrin (92.3%) and
      deltamethrin (66.7%), were used in all ranches controlling horn flies (97.5%).
      Insecticide treatments, usually incorrectly applied, were routinely delivered by
      manual backpack sprayers in most ranches (84.5%). This profile of insecticide use
      helps to explain the widespread resistance of horn flies to pyrethroids in the
      state as well as their high susceptibility to the organophosphate. Inadequate
      control practices contribute to aggravate the resistance problem and its
      consequences.

PMID- 18078602
TI  - [Transcription of genes of membrane proteins of Brazilians isolates of Anaplasma
      marginale].
AB  - This work shows the transcription profile of membrane protein genes in three
      Brazilian isolates of Anaplasma marginale (Rio Grande do Norte, Pernambuco-Zona
      da Mata, and Pernambuco-Sertao). RNA was purified from cattle blood
      experimentally-infected with the three isolates of A. marginale. After reverse
      transcription, genes omp1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, and 14; opag1-3;
      virB3, 9, and 10; am097, 197, 254, 854, and 956 were amplified by PCR, with
      specific primers. Transcripts were detected for all genes, except omp2, 3 e opag3
      in all isolates and for omp7 in one out of the three isolates analyzed. Absence
      of transcription for opag3 and omp7 diverge from the North American isolates of
      A. marginale. Reasons for such differences were discussed.

PMID- 18078603
TI  - Tyzzeria parvula (Kotlan, 1933) Klimes, 1963 (Apicomplexa: Eimeriidae) in the
      greylag goose (Anser anser Linnaeus, 1758) in southeastern Brazil.
AB  - Tyzzeria parvula from the greylag goose (Anser anser) is described in
      Southeastern Brazil. Oocysts are spherical to subspherical ranging from 12.4-180
      to 10.7-15.9 microm (15.4 X 13.4 microm), shape index 1.15, with a double layered
      wall 0.4 to 0.7 microm thick (n=20), outer smooth and colorless, inner pale
      greenish. Micropyle is absent, but oocyst residuum is present containing numerous
      granules and spherules. Surrounded by residuum there are eight sporozoites having
      one end round and other fine and slightly curved.

PMID- 18078604
TI  - [Infestation by Lynxacarus radovskyi (Tenorio, 1974) in domestic cats from
      Metropolitan Region of Recife, Pernambuco, Brazil].
AB  - This study was performed with the aim of to investigate the infestation by the
      cat fur-mite Lynxacarus radovskyi in cats from Recife Metropolitan Region, State
      of Pernambuco, Brazil, during the period of May through December of 2003. Hair
      samples were taken from cats of both sexes and different ages and submitted to
      microscopical examination. The results showed that 75.84% (254/335) of cats were
      infested with L. radovskyi, but statistically significant differences were not
      observed among the presence of mite and sex, race and age. The results indicate
      that the mite L. radovskyi is endemic in this population.

PMID- 18078605
TI  - [Natural infection by hemoparasites in calves submitted to chemoprophylaxis at 30
      days of age].
AB  - The tick-borne disease (TBD) brings great damages to cattle breeding. The most
      important etiologic agents are Babesia bigemina, B. bovis and Anaplasma
      marginale, being the tick Boophilus microplus the main vector. This work reports
      the occurrence of natural infection by hemoparasites of TBD in 36 calves with
      high ticks natural infestation submitted to chemoprophylaxis with 30 days year
      old. The blood smears from animals of different ages were analized and were found
      B. bigemina (33.3%), B. bovis (11.1%) and A. marginale (13.9%). Six animals had
      clinical symptoms (16.7%) and one dead (2.8%). The number of clinical cases
      ocurred in consequence of an association of factors as high infestation of ticks
      and low passive immunity in period that calves had not developed enough active
      immunity.

PMID- 18078606
TI  - [Haemaphysalis juxtakochi Cooley, 1946 (Acari: Ixodidae) parasitizing Mazama nana
      (Hensel, 1872) (Artiodactyla: Cervidae) in the State of Rio Grande do Sul].
AB  - The record of Haemaphysalis juxtakochi Cooley, an ixodid tick, on the brocket
      deer, Mazama nana (Hensel), represents a new report after 34 years of its last
      report in the State of Rio Grande do Sul. The tick specimens (three males and one
      female) were found in Cachoeira do Sul, RS (30 degrees 02'21''S, 52 degrees
      53'38''W). This place is elevated 72 m sea above, with an annual average
      temperature of 18.8 degrees C, and annual average rainfall of 1.438 mm. This is
      the first record of this tick species in a Cervidae and it is the second
      occurrence report for the State of Rio Grande do Sul.

PMID- 18078607
TI  - [Estimative method for quantitative sampling of Rondonia rondoni (Nematoda:
      Atractidae) parasite of fish].
AB  - The present work evaluated the number of Rondonia rondoni in intestine of
      Piaractus mesopotamicus, for difference of dry and wet weight of parasites
      samples by each host, from the relation dry weight and number of parasites.
      Totals samples of R. rondoni of 37 specimens of P. mesopotamicus for attaiment of
      wet weight, dehydrated in stove with temperature between 55 degrees C and 60
      degrees C, the wet weight was measured after 24 h. The number of parasites was
      calculated with rule of three, considering the average number of 1,010 +/- 6.027
      specimens quantified in previous assay. The equation of linear regression is y =
      13.138x - 162.01 and r(2) = 0.9989. The normality of the data was proven with
      Kolmogorov-Smirnov (p < 0.01).

PMID- 18078608
TI  - [Ticks (Acari: Ixodidae) collected in the Natural Reserve of the Vale do Rio
      Doce, Linhares, State of Espirito Santo].
AB  - We confirm, after decades without new registers, the occurrence of the ticks
      Amblyomma obolongoguttatum Koch, 1844, A. brasiliense Aragao, 1908, and A.
      humerale Koch, 1844 in the State of Espirito Santo, Brazil, besides the first
      record of A. naponense (Packard, 1869) in this state.

PMID- 18078609
TI  - [Development of the fungi Metarhizium anisopliae (Metschnikoff, 1879) Sorokin,
      1883 and Beauveria bassiana (Balsamo) Vuillemin, 1912 on the Ctenophephalides
      felis felis (Bouche, 1835)].
AB  - The flea Ctenocephalides felis felis is a parasite that causes allergic
      dermatitis and also may transmit etiologic agents to domestic animals and humans.
      This study investigated by scanning electron microscopy the development of
      entomopathogenic fungi on flea cuticle. Fleas were exposed to conidia (10(8) ml(
      1)) of Metarhizium anisopliae (isolate 959) or Beauveria bassiana (isolate 986).
      Following standard protocols for electron microscopy, the specimens were prepared
      2, 15, 26 and 96 h after infection. The micrography revealed that 2 h after
      fungus exposure, conidia attachments encompassed the entire flea cuticle,
      especially on abdominal intersegmental membranes. The emergence of germ tubes and
      appressoria formation occurred at 15 h, thickening and branching of hyphae on the
      flea cuticle was noted at 26 h. Therefore, both of these fungal isolates were
      able to develop on cuticular surfaces of C. f. felis.

PMID- 18078610
TI  - Nailfold capillaroscopy and classification criteria for systemic sclerosis.

PMID- 18078611
TI  - Response criteria for cutaneous SLE in clinical trials.
AB  - Systemic lupus erythematosus (SLE) is a complex phenotype characterized by a wide
      variety of clinical manifestations but the skin is involved in 70-80% of
      patients. Acute cutaneous lupus erythematosus lesions, like other organ
      manifestations of SLE wax and wane with other manifestations of active disease
      and quantifying it is a useful a "signal" to screen new therapies in SLE and pre-
      and post-treatment biopsies can be additionally informative. The ACR has
      recommended a priori response criteria for SLE Activity Measures (2) and that
      these be used along with organ specific response criteria in clinical trials. We
      review the literature on evaluation of skin manifestations in lupus erythematosus
      (LE) and propose the parameters of evaluating responsiveness and criteria for
      minimal clinically important changes in skin manifestations. The Committee
      presents two options for grading skin manifestations. These recommendations add
      to the tools of SLE trials.

PMID- 18078612
TI  - Ultrasound imaging for the rheumatologist XI. Ultrasound imaging in regional pain
      syndromes.
AB  - Regional pain syndromes (RPS) are common complaints in clinical rheumatological
      practice. Ultrasound (US) allows a detailed assessment of soft tissue involvement
      and its use may have considerable impact on the management of RPS. The present
      review provides an update of the available data about US imaging in RPS together
      with research issues relating to periarticular soft tissue pathology. The
      research agenda covers: definition of standard scanning protocols for US
      examination of the most common RPS assessed by the rheumatologist and the
      clinical impact of US findings in the management of patients with RPS.

PMID- 18078613
TI  - Anti-TNF-alpha treatment in rheumatoid arthritis with anti-Ro/SSA antibodies.
      Analysis of 17 cases among a cohort of 322 treated patients.
AB  - OBJECTIVE: To compare the efficacy and safety of anti-TNF-alpha treatment in RA
      patients with and without anti-Ro antibodies, in order to detect any change in
      their immunological or clinical profile. METHODS: Autoantibodies in 322 patients
      being treated with anti-TNF-alpha drugs were studied; 17 were found to be anti-Ro
      positive, while 305 were anti-Ro negative. RESULTS: Two groups, comparable in
      terms of sex distribution, RA duration and anti-TNF-alpha drug employed, showed
      symmetrical, erosive polyarticular RA with high disease activity. Anti-TNF-alpha
      led to significant improvement in both groups. At baseline rheumatoid factor and
      ANA, globally positive in 68.6% and 40%, were more frequent in anti-Ro positive
      sera. ANA showed a rising trend beginning in the 6th month of treatment in both
      groups, which was always statistically significant compared to baseline. Anti
      dsDNA antibodies, measured using either CLIFT and ELISA or the Farr assay,
      remained stable in the first 6 months, then increased at 12th and 18th month, and
      subsequently declined. No difference was detected between the two groups
      regarding the number or cause of dropouts, but lupus-like disease was more
      frequent in anti-Ro positive subjects (p = 0.012). In addition, two cases of NHL
      were detected. CONCLUSION: Anti-TNF-alpha treatment was shown to be effective in
      patients with anti-Ro antibodies. Although anti-dsDNA and lupus-like disease were
      more frequent in anti-Ro positive patients, severe manifestations of systemic
      involvement were not observed. A longer follow-up is warranted to evaluate the
      risk of NHL in these patients.

PMID- 18078614
TI  - Serum IL-1beta levels are associated with the presence of erosions in recent
      onset rheumatoid arthritis.
AB  - OBJECTIVE: To study interleukin (IL)-1beta levels in recent onset RA patients
      treated either with combination DMARD therapy (sulfasalazine, methotrexate,
      hydroxychloroquine) or a single DMARD therapy. METHODS: Serum IL-1beta levels
      were measured before the treatment and 6 months after the institution of either
      single or combination DMARD therapy using a high sensitivity ELISA method.
      Radiographic evaluation of the hands and feet was performed at 0 and 24 months.
      RESULTS: Significant correlations (r = 0.28, 95% CI 0.10-0.45) were found between
      IL-1beta levels measured at 0 and 6 months. The IL-1beta levels at 0 months
      correlated significantly (r = 0.23, 95% CI 0.03-0.4, p= 0.021) with the baseline
      number of eroded joints at 0 months but not with radiographic joint damage at 24
      months. The baseline level of IL-1beta was a better indicator for the presence of
      eroded joints than the baseline level of serum CRP. No significant changes in IL
      1beta levels were observed during the first 6 months of anti-rheumatic treatment
      in either group. No statistically significant difference between IL-1beta levels
      in the patients with or without the shared epitope could be observed.
      CONCLUSIONS: The serum IL-1beta level is significantly associated with the
      presence of erosions at the onset of RA but its predictive value is attenuated or
      lost when single or combination DMARD medication is instituted. Measuring IL
      1beta at the time of diagnosis in a single patient cannot be used to estimate the
      erosive nature of the disease or the prognosis.

PMID- 18078615
TI  - Morphological, immunocytochemical and biochemical studies in human osteoarthritic
      chondrocytes exposed to IL-1b and cyclical hydrostatic pressure.
AB  - OBJECTIVE: To investigate the in vitro effects of cyclic hydrostatic pressure
      (HP), of a magnitude and frequency close to those that presumably exist in
      articular cartilage, on human osteoarthritic chondrocytes cultivated for 48 hrs
      in the presence or absence of interleukin-1beta (IL-1beta). METHODS:
      Pressurization cycles in the form of sinusoidal waves (minimum pressure 1 MPa,
      maximum pressure 5 MPa) at a frequency of 0.25 Hz for 3h were assessed on
      cultured chondrocytes obtained from the femoral heads of osteoarthritic patients.
      Under these conditions, we evaluated proteoglycan (PG) levels and nitrites
      production in the culture medium by the immunoenzymatic method and examined the
      morphology of chondrocytes by transmission electron microscopy (TEM). Moreover,
      immunocytochemical investigations were performed to localize inducible nitric
      oxide synthase (iNOS). RESULTS: The presence of IL-1beta led to a very
      significant decrease in PG levels and to an increase in NO production. When the
      chondrocytes were cultured in the presence of HP, a statistically significant
      restoration of PG levels was observed, but pressurization did not significantly
      increase the PG levels in cells damaged by IL-1beta. After pressurization, there
      was a slight decrease in the concentration of NO under basal conditions and a
      statistically significant decrease in the IL-1beta induced release of NO. The
      results concerning metabolic production were further confirmed by the
      morphological findings obtained by TEM and immunocytochemical studies.
      CONCLUSION: This study confirms the protective role of HP which stimulates PG
      production and counteracts IL-1beta induced NO release. These data are supported
      by morphological and immunocytochemical findings.

PMID- 18078616
TI  - Simvastatin inhibits cytokine production and nuclear factor-kB activation in
      interleukin 1beta-stimulated synoviocytes from rheumatoid arthritis patients.
AB  - OBJECTIVES: Recent studies demonstrated in vivo the effectiveness of statins in
      reducing the inflammatory response in rheumatic diseases, and still more
      recently, simvastatin has been reported to inhibit in vitro IL-6 and IL-8
      production by unstimulated fibroblast-like-synoviocytes (FLS) from rheumatoid
      arthritis (RA) patients. However, no data are available on the effect of statins
      on the production of these cytokines induced by IL-1, which plays a crucial role
      in joint inflammation in the course of active RA in vivo. METHODS: In 12 RA
      patients, synovial tissue specimens were taken to obtain cultures of FLS.
      Cultures were incubated with IL-1 +/- simvastatin (5-50 micromol/l), and IL-6 and
      IL-8 production was evaluated (ELISA), also following the addition of mevalonate
      and its isoprenoid derivatives. Moreover, nuclear factor-kB (NF-kB) activation
      (immunocytochemistry and Western Blot analysis) were also evaluated. RESULTS:
      Culture incubation with IL-1 produced a dramatic increase (up to 40-fold) in
      cytokine production with respect to unstimulated cells. Simvastatin significantly
      inhibited (about 20%) IL-6 and IL-8 production from IL-1-stimulated FLS. This
      effect was completely reverted by the concomitant incubation with mevalonate or
      geranylgeraniol (but not farnesol or squalene). Moreover, simvastatin produced a
      clear-cut inhibition of IL-1-induced NF-kB activation. CONCLUSION: Simvastatin
      significantly inhibits the production of IL-6 and IL-8 also in IL-1-stimulated
      FLS, even though to a lesser extent than in unstimulated cells, via a HMG-CoA
      reductase block with an interference in prenylation process and NF-kB activation.
      Our results further support the rationale for the use of statins in the treatment
      of rheumatoid synovitis.

PMID- 18078617
TI  - Functional disability in France and its relationship with health-related quality
      of life - a population-based prevalence study.
AB  - OBJECTIVE: To estimate the prevalence of functional disability in France and
      assess its association with the health-related quality of life (HRQoL). METHODS:
      Each member in 8,000 households randomly selected in the Lorraine population were
      mailed a questionnaire asking about their sociodemographic characteristics; the
      presence of chronic locomotor or non-rheumatic diseases; functional disability on
      the Health Assessment Questionnaire (HAQ); and HRQoL on the Duke Health Profile.
      The prevalence of functional disability was described, and its relationship with
      HRQoL was assessed by logistic regression analysis. RESULTS: Among the 6,148
      subjects who responded (mean age 46 years +/- 18.3, 48% men), the prevalence of
      moderate (HAQ >or= 1) and severe (HAQ >or= 2) functional disability, adjusted for
      age and sex, was 6.5% and 1.6% respectively. HRQoL was significantly low in all
      dimensions for subjects with severe functional disability. Functional disability
      of locomotor origin significantly affected the physical (OR = 10.6 [5.1-22.1]),
      mental (OR = 4.4 [2.5-7.8]), and social (OR = 2.4 [1.4-4.3]) dimensions, with a
      threshold effect according to the disability level and perceived health (OR= 10.6
      [5.8-19.4]), with a cause-effect relationship. CONCLUSION: The prevalence of
      reported (i.e., not observed) functional disability in terms of its impact on
      HRQoL helps physicians to better understand its differential consequences, which
      should ease patient dependence, facilitate the analysis of health care needs and
      the development of prevention measures, and improve the HRQoL of patients and
      their families.

PMID- 18078618
TI  - Effect of cyclosporine A on bone density in female rheumatoid arthritis patients:
      results from a multicenter, cross-sectional study.
AB  - OBJECTIVE: To analyze the influence of cyclosporine A (CYA) on bone using data
      from a large multicenter, cross-sectional study on bone mineral density (BMD) in
      rheumatoid arthritis (RA). METHODS: We selected 558 female patients with RA and
      divided them into two groups on the basis of CYA use: those who had never used
      CYA (n = 467) and CYA users (n = 91; users for < 24 months n = 50; users for > 24
      months n = 41). Demographic, disease and treatment-related variables were
      collected for each patient. BMD was measured at the lumbar spine and proximal
      femur using dual x-ray absorptiometry. Data was analyzed by means of a univariate
      and multivariate statistical procedure. Osteoporosis (OP) was defined as BMD < 
      2.5 T score. RESULTS: The frequency of OP among non-CYA users and CYA users was
      28.2% and 33.3% (p=NS) for the lumbar spine, and 34.2% and 31.3% (p=NS) for the
      femoral neck, respectively. The prevalence of fragility fractures was not
      significantly different between the two groups. Mean values for the T-score at
      either the lumbar spine or the femoral neck were comparable in the two groups,
      even after adjustment for age, menopausal status, body mass index (BMI), Health
      Assessment Questionnaire (HAQ) score and steroid use. The generalized linear
      model showed that age, BMI and the HAQ score were significant independent
      predictors of BMD at the lumbar and femoral levels, whereas CYA use was not.
      Logistic analysis showed that only age, the HAQ score and BMI were significantly
      associated with the risk of OP. However, the duration of CYA therapy > 24 months
      was associated with an adjusted decreased lumbar BMD and a significantly
      decreased femoral neck BMD (p = 0.01). The frequency of femoral neck OP in
      patients on CYA for > 24 months was significantly higher than in patients on CYA
      for < 24 months: 46.4% vs. 19.44% (p=0.03), while the prevalence of fragility
      fractures did not differ significantly: 23.1% vs. 16.6%, respectively (p=NS).
      Logistic analysis showed that CYA use was an independent predictor of
      osteoporosis at the femoral site. CONCLUSION: Long-term CYA therapy may have
      negative effects on BMD in female RA patients.

PMID- 18078619
TI  - Comparison of anti-agalactosyl IgG antibodies, rheumatoid factors, and anti
      cyclic citrullinated peptide antibodies in the differential diagnosis of
      rheumatoid arthritis and its mimics.
AB  - OBJECTIVE: Anti-agalactosyl IgG antibodies [anti-Gal(0) IgG] have been regarded
      as a useful serological marker for rheumatoid arthritis (RA). Our aim was to
      evaluate the clinical usefulness of anti-Gal(0) IgG in the differential diagnosis
      of rheumatic disorders that mimic RA compared to rheumatoid factors (RF) and anti
      cyclic citrullinated peptide antibodies (anti-CCP). METHODS: Sera were collected
      from 39 patients with RA, 49 patients with primary Sjogren's syndrome (pSjS), 47
      patients with systemic lupus erythematosus (SLE), 65 patients with chronic
      hepatitis B viral infection (HBV), 68 patients with chronic hepatitis C viral
      infection (HCV) and 19 normal individuals. RF-IgM was measured by the
      nephelometeric method, and RF-IgA, anti-Gal(0) IgG and anti-CCP were measured by
      the respective ELISA assays. RESULTS: Anti-Gal(0) IgG titers were remarkably
      elevated in patients with RA (191.0 +/- 250.8 AU/ml) compared to pSjS (37.9 +/-
      42.6 AU/ml), SLE (10.3 +/- 13.6 AU/ml), chronic HBV with (36.1 +/- 38.4 AU/ml) or
      without rheumatic symptoms (9.6 +/- 19.4 AU/ml), RF(+) chronic HCV without
      rheumatic symptoms (19.0 +/- 14.8 AU/ml), chronic HCV with rheumatic symptoms
      (15.2 +/- 17.4 AU/ml) and healthy individuals (2.6 +/- 0.7 AU/ml). The
      specificity of anti-Gal(0) IgG could be greatly enhanced by elevating the cut-off
      value from 12 AU/ml to 40 AU/ml (68.6% vs. 85.6%, p < 0.001) without
      significantly compromising its sensitivity (76.9% vs. 61.5%, p > 0.05).
      CONCLUSION: The serum titer of anti-Gal(0) IgG is much higher in rheumatoid
      arthritis than in mimicking diseases. The specificity of anti-Gal(0) IgG is
      enhanced when the cut-off value is raised. However, anti-CCP remains the most
      specific biomarker for RA.

PMID- 18078620
TI  - Disease-modifying effects of long-term cyclic iloprost therapy in systemic
      sclerosis. A retrospective analysis and comparison with a control group.
AB  - OBJECTIVE: To evaluate the role of iloprost, a derivative of prostacyclin, as a
      possible disease-modifying agent for systemic sclerosis (SSc). METHODS: Fifty-six
      consecutive SSc patients treated for a median period of 4 years with cyclic
      infusions of iloprost for severe Raynaud's phenomenon and ischemic ulcers were
      compared with 56 control patients matched for age, sex, disease subset and
      duration. Control patients were also similar to the iloprost group with regard to
      autoantibody status, the presence of major disease-related organ manifestations
      at baseline, and the use of other treatments. The evolution of lung function test
      results, the frequency of major disease-specific complications and the survival
      of the cohorts were the objects of this analysis. RESULTS: No significant
      difference was observed between the two groups with regard to changes in lung
      function tests over time, or the number of patients who presented with the onset
      of active interstitial lung disease, pulmonary arterial hypertension or
      scleroderma renal crisis. Survival did not differ between the two groups.
      CONCLUSION: The evolution of lung function test results, the frequency of major
      disease-specific complications, and survival did not differ significantly between
      SSc patients treated with cyclic iloprost and a group of patients matched for
      sex, age, and disease subset and duration. However, no cases of severe pulmonary
      arterial hypertension were observed in the patients treated with iloprost,
      suggesting that studies focusing on the possible preventive action of iloprost on
      the progression of SSc- associated mild pulmonary arterial hypertension would be
      warranted.

PMID- 18078621
TI  - Improving trends in glucocorticoid-induced osteoporosis management: 2002 to 2006.
AB  - OBJECTIVE: In 2002 we undertook an audit of GIO (glucocorticoid-induced
      osteoporosis) management in the outpatient clinics of our university teaching
      hospital and found a wide variation in practice and considerable under-treatment
      of patients. We re-audited our practice in 2006. METHODS: A retrospective chart
      audit was undertaken over a 4-month period of 3,475 patients attending the 3
      medical specialty outpatient clinics that were originally audited in 2002. All
      glucocorticoid (GC) users over the past 6 months were identified. Demographic
      data and treatment details were extracted, and findings were compared with the
      previous audit. RESULTS: Two hundred and fifty-three (7%) patients were
      identified to be taking GC vs. 104 (2%) in 2002. GIO risk was documented in 71%
      (179) (p < 0.001) of the charts vs. 13% (19) in the previous audit. In 2002, 56%
      (58) were on some form of bone protection [53% (55) on Ca/vitamin D and 29% (30)
      on a bisphosphonate] whereas in 2006 the figures were 86% (219), 82% (207) and
      57% (144), respectively. DXA scanning was performed in 32% (82) of our patients
      in 2006. Nonetheless, considerable variation in practice was still seen, with
      prescription rates for anti-resorptive therapy varying from 24%-70% and those for
      Ca/vitamin D supplements ranging from 15%-95% for different services. For the
      highest risk patients, the prescription rates by specialty ranged from 36%-72%
      for anti-resorptive therapy and 76%-95% for Ca/vitamin D supplements. CONCLUSION:
      Over 4 years, major improvements in GIO management have taken place in our
      institution, with almost a doubling of the prescription of bone protectants.
      However, there still remains a considerable variation in individual practices and
      an under-utilisation of DXA scanning. We believe that these overall, encouraging
      findings can be generalized to similar institutions elsewhere.

PMID- 18078622
TI  - Determinants of pulmonary function improvement in patients with scleroderma and
      interstitial lung disease.
AB  - BACKGROUND: In patients with scleroderma-related interstitial lung disease (ILD),
      improvements of pulmonary function have been reported after treatment with
      cyclophosphamide (CYC) alone or CYC and high-dose steroids. The study objective
      was to identify therapeutic regimen that alone or in combination with laboratory
      or clinical characteristics were associated with pulmonary function improvement
      in these patients. METHODS: Scleroderma patients with ILD and serial pulmonary
      function measurements were retrospectively analyzed. We recorded forced vital
      capacity (FVC, % predicted), diffusion capacity (DLCO, % predicted), type of
      therapy, and various clinical and laboratory parameters. Treatment with IV CYC
      was recorded as cumulative dose (grams) and treatment with steroids as high or
      low dose; outcome was defined as a sustained increase in FVC (% predicted) >or=
      10 points. RESULTS: Of the 59 patients who were included in the study, 29 (49 %)
      patients received IV CYC (cumulative dose 13.9 +/-6.2, range 5.2-26.2 gr) for 3.3
      +/- 2.4 years (range 5-60 months). Eighteen out of 59 (30 %) patients received
      high-dose prednisolone and 41 (70 %) received low-dose prednisolone. In an
      ordinal logistic model, patients receiving > 12 gr of CYC were 6 times more
      likely to improve FVC than to decrease or maintain FVC, compared to those who did
      not receive CYC (p = 0.02). In multivariate analysis, the effect of high dosage
      CYC on FVC persisted (OR 10.82, p = 0.02). Steroid dosage (high or low) was not
      associated with FVC improvement (p < 0.05). CONCLUSION: In patients with
      scleroderma and ILD, treatment with CYC is the only variable that is
      independently associated with pulmonary function improvement and that prolonged
      (> 1 year) CYC therapy increases the probability of pulmonary function
      improvement more than shorter CYC courses.

PMID- 18078623
TI  - RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro.
AB  - Ligands for the receptor for advanced glycation endproducts (RAGE) are increased
      in RA synovial fluid (SF), serum and synovium. Since RAGE is present on
      fibroblast-like synoviocytes (FLS), the present study investigates whether the
      RAGE ligands HMGB-1 and AGEs are able to stimulate the characteristic,
      pathological invasive behaviour of these cells. FLS were obtained during joint
      replacement surgery. FLS were seeded in serum free medium with HMGB-1 or glycated
      albumin (BSA-AGE) on transwell filters coated with Matrigel. The lower
      compartment contained medium with serum as a chemoattractant. After three days,
      the percentage of invading cells was determined and compared to the control
      invasion. Stimulation with HMGB-1 increased invasiveness to 125% compared to the
      control (p = 0.001). Addition of anti-RAGE antibody reduced this back to baseline
      (98%, p = 0.002). Stimulation with BSA-AGE, another RAGE ligand, increased
      invasiveness to 150% compared to the control (p = 0.003). Addition of anti RAGE
      was again able to reduce the increased invasiveness back to baseline (95%, p =
      0.008). HMGB-1 and BSA-AGE stimulated the invasiveness of RA-FLS by activation of
      RAGE. As such, RAGE may be an interesting target for therapy directed at the
      inhibition of synoviocyte activation.

PMID- 18078624
TI  - Etanercept therapy in patients with a positive tuberculin skin test.
AB  - INTRODUCTION: Etanercept (Enbrel), a tumor necrosis factor-alpha (TNF-alpha)
      antagonist, is commonly used for the treatment of a variety of rheumatic
      diseases. Tuberculosis (TB) infections have been associated with chronic TNF
      alpha blocking therapy, and there is concern that such therapy may predispose
      patients to TB reactivation. In this study, we attempted to evaluate the
      frequency of latent TB reactivation among patients treated with etanercept.
      METHODS: All patients with either a positive purified protein derivative (PPD)
      for TB or a previous history of therapy for latent TB infection (LTBI) who were
      prescribed etanercept in the division of rheumatology at John H. Stroger Jr
      Hospital of Cook County prior to November 2005 were enrolled in this study. A
      retrospective chart review was performed looking for evidence of active TB
      infection during etanercept treatment. RESULTS: Forty-eight patients with a
      positive PPD were treated with etanercept, and followed for an aggregate of 818
      patient-months of etanercept exposure, with a mean follow-up period of 17 months
      (range 5 to 48 months); all patients had at least one follow-up visit. Forty-four
      patients (92%) were fully or partially treated with LTBI therapy prior to
      initiation of etanercept. Chest roentgenograms were available for review in 43
      patients, ten of which had evidence of old granulomatous disease. No cases of
      active TB were described during the study period. CONCLUSIONS: In this small
      retrospective analysis, none of the 48 patients with positive PPDs who were
      treated with etanercept for average of 17 months developed active TB.

PMID- 18078625
TI  - Discordance between erythrocyte sedimentation rate and C-reactive protein
      measurements: clinical significance.
AB  - OBJECTIVE: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are
      common measures of systemic inflammation. Our goal was to identify clinical
      factors associated with CRP/ESR discordance. METHODS: We identified patients with
      ESR and CRP results at our academic hospital over six months. We matched
      individuals with discordant results (one measure in highest tertile, other in
      lowest), by age and sex to those with non-discordant results, and reviewed
      medical records for laboratory and clinical factors. We employed analysis of
      variance (ANOVA) and Chi squared tests to compare these variables in discordant
      and non-discordant subjects. We used conditional logistic regression to estimate
      the relative risk of CRP/ESR discordance associated with each variable. RESULTS:
      2,069 patients had CRP and ESR measured on the same day; 87 had discordant
      results, 55 (2.6%) with elevated ESR/low CRP, 32 (1.5%) with elevated CRP/ low
      ESR. Underlying infection was associated with > 14 fold risk of elevated ESR/low
      CRP discordance (p < 0.001). Renal insufficiency was associated with increased
      risk of elevated ESR/low CRP discordance, (p = 0.003). RA patients were slightly
      less likely to have elevated ESR/low CRP, (p = 0.008, NS after Bonferroni
      correction). Low serum albumin was associated with both kinds discordance.
      CONCLUSION: Infection, renal insufficiency, and low albumin were associated with
      having elevated ESR/low CRP; low albumin predicted elevated CRP/low ESR and
      elevated ESR/low CRP discordance. RA patients were less likely to have elevated
      ESR/depressed CRP. ESR as a measure inflammation in systemic rheumatic disease
      may be limited in settings of infection, renal insufficiency, and low albumin.

PMID- 18078626
TI  - Lack of association of a functional single nucleotide polymorphism of PTPN22,
      encoding lymphoid protein phosphatase, with susceptibility to Henoch-Schonlein
      purpura.
AB  - OBJECTIVE: To assess the possible association between the PTPN22 gene 1858C-->T
      polymorphism and the susceptibility to Henoch-Schonlein purpura (HSP) and
      determine if this polymorphism is implicated in the severity of this systemic
      vasculitis. PATIENTS AND METHODS: Fifty-seven unselected patients from Northwest
      Spain with primary systemic vasculitis, classified as HSP according to previously
      proposed criteria, with a follow-up of at least 2 years and 229 healthy controls,
      were included in this study. All the individuals were of Spanish Caucasian
      origin. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by
      real time PCR technology, using TaqMan 5' allelic discrimination assay. RESULTS:
      No significant differences in allele or genotype distribution frequencies for the
      PTPN22 gene polymorphism were observed between HSP patients and controls. It was
      also the case when HSP patients were stratified for the presence of severe
      gastrointestinal complications (n = 46), nephritis (n= 37) or permanent renal
      involvement (renal sequelae) (n = 12). CONCLUSION: Our results do not support a
      potential implication of the PTPN22 gene polymorphism in the susceptibility to
      and clinical expression of HSP.

PMID- 18078627
TI  - Improving the sensitivity of the American College of Rheumatology classification
      criteria for systemic sclerosis.
AB  - OBJECTIVE: A large proportion of patients with limited systemic sclerosis (SSc)
      do not meet the current American College of Rheumatology (ACR) classification
      criteria for SSc. We undertook this study to determine whether the addition of
      easily available clinical variables, namely nailfold capillary abnormalities
      identified using a dermatoscope and visible telangiectasias, could improve the
      sensitivity of the current ACR classification criteria for patients with limited
      SSc. METHODS: Patients in the Canadian Scleroderma Research Group Registry with
      skin involvement distal to the metacarpophalangeal joints were identified and
      divided into two groups according to whether they fulfilled the current ACR
      classification criteria for SSc or not. Sensitivity of the criteria was
      calculated. Regression tree analysis was performed to determine whether the
      addition of nailfold capillary abnormalities identified using a dermatoscope and
      visible telangiectasias could improve the sensitivity of the criteria. RESULTS:
      One hundred and one (101) patients were included, in majority women with a mean
      age of 59 (+/- 13). Of these, 68 (67%) met the ACR classification criteria. The
      sensitivity of the criteria increased from 67% to 99% with the addition of
      nailfold capillary abnormalities identified using a dermatoscope and visible
      telangiectasias. CONCLUSIONS: The SSc research community would benefit from
      having better classification criteria to identify patients with limited SSc. The
      current classification criteria for SSc may be significantly improved by the
      inclusion of easily identified clinical variables including nailfold capillary
      abnormalities using a dermatoscope.

PMID- 18078628
TI  - Severe systemic inflammatory response syndrome in a patient with adult onset
      Still's disease treated with the anti-IL1 drug anakinra: a case report.
AB  - Interleukin 1 (IL1) plays an important role in adult onset Still's disease.
      Anakinra (Kineret), a recombinant IL1 Receptor Antagonist (IL 1 RA) was therefore
      recently proposed in adult onset Still's disease with great efficacy. Anakinra
      appeared to be well tolerated and safe. The case of a patient with refractory
      adult onset Still's disease who experienced a Systemic Inflammatory Response
      Syndrome and Adult Respiratory Distress Syndrome requiring intensive care unit
      hospitalization 10 days after the introduction of anakinra is reported.

PMID- 18078629
TI  - Sustained success of therapy with inhaled iloprost for severe pulmonary arterial
      hypertension associated with systemic sclerosis and pulmonary fibrosis.
AB  - CASE REPORT: We report here the case of a woman with diffuse cutaneous systemic
      sclerosis with pulmonary involvement and severe (WHO functional class III)
      pulmonary arterial hypertension (PAH) and recurrent cardiac decompensation. The
      simultaneous presence of primary biliary cirrhosis with markedly elevated
      transaminase levels constituted a contraindication for bosentan, which would
      otherwise have been the first-line treatment for PAH. The patient was therefore
      treated with inhaled iloprost. DISCUSSION: Once inhaled iloprost therapy had been
      started, we promptly noted a definite and sustained improvement in physical
      exercise capacity and normalisation of haemodynamic variables. In cases where
      bosentan is contraindicated, inhaled iloprost is an effective alternative for the
      treatment of severe PAH.

PMID- 18078630
TI  - Treatment of Achilles tendon calcinosis in juvenile dermatomyositis with external
      ilizarov fixator.
AB  - Calcinosis is a devastating complication of juvenile dermatomyositis and a
      challenging therapeutic problem. We report the use of an external Ilizarov
      fixator for the treatment of Achilles tendon calcinosis causing severe disability
      in a young girl with juvenile dermatomyositis.

PMID- 18078631
TI  - A review of bone pain relief with ibandronate and other bisphosphonates in
      disorders of increased bone turnover.
AB  - Several disorders of increased bone turnover and low bone mineral density (BMD)
      are associated with severe pain that is refractory to treatment with conventional
      and even opioid analgesics. Because of their ability to effectively improve the
      underlying pathogenesis of these disorders (i.e., reduce bone resorption and
      increase BMD), bisphosphonates are considered part of the palliative care of
      malignant bone-related pain and also appear to have some analgesic efficacy in
      other, non-malignant conditions. Ibandronate, a potent, nitrogen-containing
      bisphosphonate that can be given orally and intravenously, has demonstrated
      robust effects in relieving the pain associated with several malignant disorders.
      Unlike other available intravenous (i.v.) bisphosphonates, i.v. ibandronate is
      not associated with renal side effects, even at high doses such as 6 mg every 3
      weeks. In addition, oral ibandronate (50 mg daily) is currently the only oral
      bisphosphonate proven to reduce and maintain bone pain scores below baseline for
      2 years in patients with metastatic bone disease. Lower dose, less intense dosing
      regimens of ibandronate relieve bone pain in non-malignant conditions: i.v.
      ibandronate (2 mg every 3 months with or without an initial 4 mg injection)
      provides pain relief for patients with corticosteroid-induced osteoporosis,
      localised transient osteoporosis (bone marrow oedema) and sternocostoclavicular
      hyperostosis. Both oral and i.v. ibandronate are well tolerated. In conclusion,
      ibandronate offers an effective and convenient choice for the relief of bone pain
      in a wide variety of underlying bone conditions.

PMID- 18078632
TI  - Macrophage migration inhibitory factor (MIF) and oligoarticular juvenile
      idiopathic arthritis (o-JIA): association of MIF promoter polymorphisms with
      response to intra-articular glucocorticoids.
AB  - OBJECTIVES: To address the clinical relevance of macrophage migration inhibitory
      factor (MIF) promoter polymorphisms in oligoarticular juvenile idiopathic
      arthritis (o-JIA) by evaluating their associations with serum and SF MIF levels,
      with response to intra-articular glucocorticoid injections and with outcome of
      the disease. METHODS: Seventy-five Caucasian patients with o-JIA were studied.
      Alleles of the -794 CATT variable number of tandem repeats (VNTR) and of the -173
      G/C single nucleotide polymorphism (SNP) were identified by capillary
      electrophoresis following fluorescently labelled PCR and by allelic
      discrimination assay, respectively. MIF levels were measured by ELISA. The
      association of MIF promoter polymorphisms with polyarticular extension, Childhood
      Health Assessment Questionnaire (CHAQ) score at the last follow-up visit and
      occurrence of chronic anterior uveitis was evaluated only in patients with a
      follow up > 5 years. RESULTS: Neither of the MIF promoter polymorphisms was
      associated with serum MIF levels, nor with the long-term outcome of o-JIA. The 
      173 G/C SNP was significantly associated with both SF MIF levels and duration of
      response to intra-articular glucocorticoid injection. Carriers of a MIF -173 C
      allele were 4 times more likely to relapse within 3 months. No association was
      found between the different MIF CATT alleles and both SF MIF levels and duration
      of response to intra-articular glucocorticoids. CONCLUSION: Our study shows the
      clinical relevance of the MIF -173 G/C SNP in o-JIA and suggests that the -173 C
      allele may represent a predictor of poor response to intra-articular
      glucocorticoid treatment.

PMID- 18078633
TI  - Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate
      in juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To compare serial C-reactive protein (CRP) and erythrocyte
      sedimentation rate (ESR) levels in juvenile rheumatoid arthritis (JRA) patients
      and investigate their application as diagnostic parameters and prognostic
      predictive factors. METHODS: We carried out retrospective chart review among JRA
      patients who were followed-up at the National Taiwan University Hospital (NTUH)
      between 1994 and 2005. RESULTS: Thirty-nine girls and 68 boys were included in
      this study. At the time of diagnosis, the prevalence of ESR was significantly
      greater than that of CRP (86.8% vs. 47.2%, p < 0.05). ESR revealed more
      responsiveness to treatment compared to CRP (SRMs were -0.69 and -0.31,
      respectively). At the time of diagnosis, high CRP levels (>or= 5mg/dL) correlated
      with poor therapeutic response, as do positive CRP (> 0.8 mg/dL) and high ESR
      levels (> 40 mm/h) after treatment for six months. Overall, initial high CRP
      levels (>or= 5mg/dL) demonstrated the strongest predictive role of failure of the
      first remission. CONCLUSION: For disease diagnosis, ESR can be a better parameter
      than CRP but a high initial CRP level can strongly predict treatment failure of
      the first remission.

PMID- 18078634
TI  - Esophageal involvement in juvenile localized scleroderma: a pilot study.
AB  - OBJECTIVES: To evaluate the esophageal involvement in patients with juvenile
      localized scleroderma (JLS). METHODS: A cohort of patients with JLS underwent
      esophageal stationary manometry to evaluate esophageal motility and lower
      esophageal sphincter (LES) function, distal esophagus 24-hour pH-monitoring to
      detect gastroesophageal reflux (GER) and upper gastrointestinal (GI) endoscopy to
      evaluate the presence of esophagitis. RESULTS: Fourteen patients (10 female, mean
      age 13.3 yrs, mean disease duration 4.7 yrs), took part in the study. Ten had
      linear scleroderma, three deep morphea, and one generalized morphea. Esophageal
      abnormalities were found in 8/14 patients (57%): pathological acid exposure on 24
      hour pH-monitoring was found in 7; non-specific esophageal motor abnormalities in
      5 and endoscopy-proved esophagitis in 5 symptomatic patients. Interestingly, 5
      out of 8 patients with esophageal abnormalities were found to be ANA positive,
      and 2 were also RF positive. CONCLUSION: Esophageal involvement is not unusual in
      patients with juvenile localized scleroderma, even in the absence of specific
      symptoms. These preliminary findings, if confirmed in a larger cohort of
      patients, may support the indication for an extensive GI evaluation especially in
      presence of positive autoantibodies or specific GI symptoms.

PMID- 18078635
TI  - A boy with bizarre hands mimicking an inflammatory chronic disease.

PMID- 18078636
TI  - Low dose interferon-alpha to treat Behcet's disease.

PMID- 18078637
TI  - Coexistence of familial Mediterranean fever and Sjogren's syndrome in a Japanese
      patient.

PMID- 18078638
TI  - Systemic sclerosis associated with primary biliary cirrhosis (Reynolds' syndrome)
      in a pair of siblings.

PMID- 18078639
TI  - Squamous cellular carcinoma immunocomplexed is increased in scleroderma patients
      with lung fibrosis.

PMID- 18078640
TI  - Chloroquine and QTc interval.

PMID- 18078641
TI  - Sonoelastography can help in the localization of soft tissue damage in
      polymyalgia rheumatica (PMR).

PMID- 18078642
TI  - Soluble Fas and soluble Fas ligand in the joints of patients with rheumatoid
      arthritis and osteoarthritis: a Tunisian case-control study.

PMID- 18078643
TI  - [Chronic obstructive pulmonary disease seems to be more frequent than earlier
      supposed].

PMID- 18078644
TI  - [Sexual dysfunction in men treated for testicular cancer].
AB  - Patients treated for testicular cancer have a higher risk of ejaculatory,
      orgasmic and erectile dysfunctions compared with healthy males. The causality is
      not clear. In this paper we assess sexual dysfunction in the different treatment
      modalities based on primarily 1 meta-analysis and 11 original articles. During
      treatment, approximately 1/3 of patients experience one or more sexual
      dysfunctions. Only retroperitodineal surgery is significantly correlated with a
      specific sexual dysfunction, which is loss of ejaculation. Psychosexual causes
      seem to be important in the understanding of sexual dysfunctions in the aftermath
      of testicular-cancer treatment.

PMID- 18078645
TI  - [Drugs and driving].
AB  - In recent years, the problem of driving under the influence of drugs of abuse
      (DUID) has been subject to increased focus. Several European countries have
      introduced "zero tolerance" legislation regarding drugs of abuse in traffic.
      Denmark is currently preparing similar legislation. Epidemiological data suggest
      that the problem of DUID in Denmark is of similar magnitude as in comparable
      countries. Relative risk estimations for DUID are reviewed on the basis of recent
      literature.

PMID- 18078646
TI  - [Chemotherapy and radiotherapy for inoperable pancreatic cancer. A survey of a
      Cochrane review].

PMID- 18078647
TI  - [Lithium versus antidepressants in prevention of unipolar depression. A survey of
      a Cochrane review].

PMID- 18078648
TI  - [Prevalence of chronic obstructive pulmonary disease in Copenhagen. Results from
      The Copenhagen City Heart Study].
AB  - INTRODUCTION: COPD is one of the leading causes of death worldwide. No recent
      prevalence study has been carried out in Denmark, but it is estimated that
      approximately 200,000 Danes have COPD. The aim of this study was to determine the
      prevalence of COPD in Copenhagen using data from the 4th examination of The
      Copenhagen City Heart Study (CCHS from 2001-2004) and to estimate the total
      number of COPD patients in Denmark. MATERIALS AND METHODS: 6,238 people
      participated in the 4th examination of CCHS. We selected all participants aged 35
      years or older with adequate information regarding smoking habits and lung
      function for the final prevalence analyses (n = 4,908). COPD staging was done
      according to the GOLD and ERS/ATS criteria. We received information regarding the
      Danish population from The National Bureau of Statistics Denmark. RESULTS: The
      prevalence of COPD in the 4th CCHS increased with age and was higher among males
      than females. The total number of Danes with COPD is estimated to 430,000,
      270,000 of whom have clinically important COPD (GOLD 2-4) and 40,000 have severe
      COPD (GOLD 3-4). CONCLUSION: The prevalence of COPD in Denmark is higher than
      previously anticipated. The 40,000 patients with severe COPD are in immediate
      need of relevant medical treatment and rehabilitation. Danish society also needs
      to exert a substantial effort comprising early detection, prophylaxis and
      relevant treatment for the 230,000 persons with moderate COPD in order to prevent
      disease progression.

PMID- 18078649
TI  - [Diabetes passport--understanding and use among different ethnic groups of
      diabetes patients. Interviews with Turkish, Pakistani and Danish patients].
AB  - INTRODUCTION: Diabetes passports for patients have been used for years in
      hospitals in our region. Since 2004 data have been printed from the electronic
      database DiabetesRASK and a new edition of the passport is given to patients at
      each visit. One of the objectives of the passport is to serve as a pedagogic
      tool. However, patients' understanding and use of the passport has never been
      studied. MATERIALS AND METHODS: Inclusion criteria for patients: type 2 diabetes,
      born in Turkey (T) or Pakistan (P), regular attendees at the outpatient clinics
      at Hvidovre Hospital or Amager Hospital and their personal diabetes data in the
      database DiabetesRASK. A comparable group of Danish diabetes patients was
      selected. All were invited to participate in a semi-structured interview.
      RESULTS: 14 T, 11 P and 10 D patients participated in the study. 53% T and 73% P
      had the ability to read in their own language while 15% T and 55% P were able to
      read in Danish. In the groups fewer than 25% had ever shown their passport to the
      GP. Between 0% and 36% of any of the given questions were understood or
      identified correctly by T patients. Similar figures for the P and D patients were
      0-55% and 30-100%. CONCLUSION: It is demonstrated that the diabetes passport is
      not widely used by patients. Furthermore, we found poor understanding of
      information on the passport in general but with great individual variability. The
      poorest understanding was found among immigrants, which might be the result of
      language problems. However, Danish patients also had insufficient understanding
      of the information. We recommend that the diabetes passport be rewritten so that
      it is more easily understood by patients and that outpatient clinics also
      allocate more resources to the guidance of patients concerning the passport.

PMID- 18078650
TI  - [The importance of physical activity and body mass index for body satisfaction].
AB  - INTRODUCTION: Body satisfaction has mostly been investigated among patients with
      psychiatric diseases. A few studies have found an association between physical
      activity, obesity and body satisfaction in the healthy population, but the focus
      has mostly been on the risk of developing diseases. The aim of the present study
      has been to study the association between body satisfaction, BMI, physical
      activity and chronic diseases. MATERIALS AND METHODS: A total of 15,252 women and
      14,181 men born between 1953 and 1982 (both years included) and registered with
      The Danish Twin Registry answered a questionnaire which they were sent in 1994.
      We used the questions on chronic diseases, height and weight, physical activity
      and body satisfaction. Univariat analysis of body satisfaction and the other
      variables was carried out using chi2-tests and t-tests. Multivariat analysis was
      carried out with logistic regression. RESULTS: More men than women are satisfied
      with their bodies; BMI confers a negative association, while physical activity
      confers a positive association with body satisfaction. This satisfaction appears
      to some degree mediated by BMI. The presence of asthma and other lung symptoms
      and lower-back pain was negatively associated with body satisfaction. DISCUSSION:
      Thinness tends to be the ideal body image today and this may explain why more
      obese people are dissatisfied with their body. This ideal is more important for
      women s perception of their bodies. Physical activity and being healthy adds to
      body satisfaction.

PMID- 18078651
TI  - [Quadrivalent HPV 6/11/16/18 vaccine].
AB  - This randomized, double-blind study included 12,167 women who received three
      doses of quadrivalent HPV 6/11/16/18 vaccine or placebo (day 1, month 2, and
      month 6). The participants were followed for an average of 3 years. The vaccine
      prevented 98% of CIN2, CIN3 and adenocarcinoma in situ related to HPV 16 or HPV
      18 among women not previously exposed to these types, and 44% among all women
      (i.e. both those with and without previous infection). The vaccine efficacy
      against all high-grade cervical lesions, independent of causal HPV type, was
      estimated to 17%.

PMID- 18078652
TI  - [Sinus caroticus syndrome diagnosed after 43 years].
AB  - A 63-years-old male suffered from palpitations, syncope and near syncope for 43
      years. He had diagnosed paroxystic atrial fibrillation and was treated with
      betablocade, calcium antagonists, and flecanide with potentially severe
      complications. Blood tests, electrocardiography, echocardiography and myocardial
      scintigraphy were all normal. The patient was admitted for drug cessation, and at
      admittance sinus caroticus massage was performed. The patient developed an 11
      second pause in heart rhythm and was diagnosed with sinus caroticus syndrome.
      After pacemaker implantation, he was free of symptoms.

PMID- 18078653
TI  - [Coiling of common hepatic artery in life-threatening hemorrhage in a patient
      with inoperable pancreatic cancer].

PMID- 18078654
TI  - [Telemedicine in prehospital diagnosis and examination].

PMID- 18078655
TI  - [Direct referral of patients with ST-elevation acute myocardial infarction to
      primary percutaneous coronary intervention. Pre-hospital use of telemedicine and
      risk stratification].
AB  - INTRODUCTION: Primary percutaneous coronary intervention (PCI) is recommended for
      revascularisation of patients with ST-elevation acute myocardial infarction
      (STEMI) with a duration of symptoms less than 12 hours. Primary PCI is
      recommended even if the patient is to be transported from a non-invasive hospital
      to an invasive centre. Normally this transport requires an attending physician.
      This transport strategy is associated with an increased treatment delay. The aim
      of this study was to assess pre-hospital tele-transmitted electrocardiogram (tele
      ECG) and risk stratification by using a questionnaire in order to assess if
      selected patients with STEMI can be transported safely to primary PCI without an
      attending physician. MATERIALS AND METHODS: Since January 2005 Fyn Svendborg
      Hospital has received pre-hospital tele-ECG recorded in patients with suspected
      acute coronary syndrome (ACS) with simultaneous risk stratification by using a
      questionnaire. Transportable STEMI patients were referred directly to an invasive
      centre without an attending physician. RESULTS: During a period of 17 months tele
      ECGs were recorded from 1,148 patients. 82 patients had STEMI and 71 patients
      were transported to an invasive centre without an attending physician. In this
      group, 1 case of resuscitated ventricular fibrillation was reported. 11 patients
      were transported to the nearest hospital: 2 to invasive centres, 7 patients were
      inter-hospital transported with a physician, and transport was not
      relevant/possible for 2 patients. CONCLUSION: Pre-hospital tele-ECG and risk
      stratification can select patients with STEMI and transport them safely to an
      invasive PCI centre without an attending physician.

PMID- 18078656
TI  - [Exercise-induced inspiratory stridor. An important differential diagnosis of
      exercise-induced asthma].
AB  - Recent studies suggest that exercise-induced inspiratory stridor (EIIS) is an
      important and often overlooked differential diagnosis of exercise-induced asthma.
      EIIS is characterised by astma-like symptoms, but differs by inspiratory
      limitation, fast recovery, and a lack of effect of inhaled bronchodilators. The
      prevalence of EIIS is reported to be 5-27%, and affects both children and adults.
      The pathophysiology, the pathogenesis, and the treatment of the condition are not
      yet clarified. At present, a population-based study is being conducted in order
      to address these points.

PMID- 18078657
TI  - [Varenicline--a new drug for smoking cessation].
AB  - Varenicline is a new drug for smoking cessation that reduces cravings by binding
      to the alfa4-beta2-nicotine-achethylcholine receptors in the brain (partial
      agonist). Varenicline for 12 weeks was found to be effective for smoking
      cessation and more effective than bupropionSR after 3 months. The adverse events
      were mild with transient nausea reported by less than one third of the subjects.
      Varenicline should be used for smoking cessation when nicotine replacement
      products have failed or are undesired.

PMID- 18078658
TI  - [Circumcision and reduction of HIV infection! A new significance of this surgical
      intervention?].

PMID- 18078659
TI  - [Treatment of patients with type 2 diabetes mellitus with pioglitazone. A survey
      of a Cochrane review].

PMID- 18078660
TI  - [Biphosphonates and prostatic cancer. A survey of a Cochrane review].

PMID- 18078661
TI  - [Chronic ischemic heart failure. Revascularization improves survival among
      patients with hibernating myocardium].
AB  - INTRODUCTION: Patients with ischemic heart failure and reversible dysfunctional
      myocardium (Hibernating myocardium, HIB) can benefit from revascularization.
      These patients can be selected with nuclear methods. The purpose of this study
      was to describe the results of the imaging procedures in patients tested for HIB
      and relate the results to the choice of treatment and cause of death. MATERIALS
      AND METHODS: During a 2-year period 51 patients were referred to determine the
      amount of HIB. This can be determined with blood flow and metabolic imaging of
      the heart. Resting-myocardial perfusion imaging was performed with 99mTc
      sestamibi and glucose metabolism was visualized with 18F-fluorodeoxyglucose (18F
      FDG) gamma camera PET. Medical records and death certificate were reviewed
      retrospectively. RESULTS: 50 patients were included. We found an increased
      survival among patients with HIB who underwent revascularization (1 year
      mortality 6% vs. 33%, p = 0,004). Patients with HIB who did not undergo
      revascularization had an increased risk of sudden death. (5/15 patients vs. 0/35
      patients, p = 0,003). CONCLUSION: Despite a simplified method we find the same
      increased mortality among medically-treated patients with HIB as in earlier
      studies. This and earlier studies are all retrospective with the risk of
      selection bias. Prospective studies are underway. Nuclear imaging is useful in
      evaluating patients with heart failure before revascularization.

PMID- 18078662
TI  - [Vascular surgical procedures in Denmark 1996-2004. Own vascular surgical
      services associated with a higher incidence of operations].
AB  - INTRODUCTION: International studies indicate that decentralised vascular surgical
      activity could have a positive influence on the organisation of vascular services
      in Denmark. MATERIALS AND METHODS: Numbers of vascular operations in 1994-2004 in
      the various Danish counties were collected from the Danish National Vascular
      Registry (www.karbase.dk). Incidences were compared by z-test. P-values were
      corrected by the Bonferroni method. RESULTS: The incidence of operations for
      carotid stenosis, critical lower limb ischaemia, and acute lower limb ischaemia
      68% (P<0.01), 26% (P < 0.01), and 16% (p < 0.01) higher in counties with own
      vascular surgical services compared to counties without own vascular service. The
      incidence of operations for carotid stenosis was 22% higher in counties offering
      such operations compared to counties offering most other vascular surgical except
      carotid thrombendarterectomies (P < 0.001). CONCLUSION: Own vascular surgical
      services in Denmark are associated with a higher incidence of operations, thus
      preventing stroke and amputation.

PMID- 18078663
TI  - [Children as victims of homicide 1972-2005].
AB  - INTRODUCTION: Child homicides are rare but serious crimes. In this study the
      homicide rate and the development in the crime pattern will be investigated.
      MATERIAL AND METHODS: The investigation is retrospective and comprises the 34
      years during which the Institute of Forensic Medicine in Odense has existed.
      During this period 41 children under the age of 15 were killed in 30 episodes.
      RESULTS: The most frequent method of homicide was manual strangulation, and the
      second most frequent was blunt violence. It is demonstrated that the incidence of
      child homicide has decreased considerably compared to a previous investigation
      comprising all of Denmark. By far the largest decrease is in homicides committed
      by women against their own children, which have often been followed by suicide
      (family homicides). The decrease in family homicides committed by men is much
      less. Today men commit family homicides 8 times as frequently as women in the
      area under investigation. DISCUSSION: A possible explanation for the decreasing
      number of homicides committed by women against their own children is the
      decreased use of gas for cooking, whereby a frequent homicide method disappeared,
      and by improved socio-economic life conditions and gender balance. Men are now
      responsible for the majority of family homicides. Preventative measures for men
      in socially traumatic situations such as a divorce are recommended.

PMID- 18078664
TI  - [A 48-year-old woman's survival from a massive verapamil overdose].
AB  - We present a case report of survival from a massive verapamil overdose. The
      patient, a 48-year-old female, was admitted 12 hours after suicidal ingestion of
      10.08 grams of Isoptin Retard, a sustained release calcium channel blocker. On
      admittance, the patient had altered mental status, was hypotensive, and ECG
      showed bradycardia with nodal rhythm. The patient was treated with activated
      charcoal, colloids, crystalloids, norepinephrine, isoprenalin and epinephrine
      infusion, high dose glucose-insulin infusion and calcium. The patient was
      discharged for rehabilitation after two weeks.

PMID- 18078665
TI  - [Neurological symptoms and acute hepatitis associated with parvovirus B19].
AB  - The spectrum of symptoms correlated to parvovirus B19 infections has expanded
      greatly during the past years. We report a case of anaemia, encephalitis-like
      symptoms and acute hepatitis in a 15-months-old Danish girl associated with
      parvovirus B19, verified by positive serum IgM og IgG antibodies. She presented
      with non-febrile seizures and decreased level of consciousness. Later she
      developed signs of acute hepatitis. The course was benign.

PMID- 18078666
TI  - Fractal dimension of 40 MHz intravascular ultrasound radio frequency signals.
AB  - OBJECTIVE: Fully automatic tissue characterization in intravascular ultrasound
      systems is still a challenge for the researchers. The present work aims to
      evaluate the feasibility of using the Higuchi fractal dimension of intravascular
      ultrasound radio frequency signals as a feature for tissue characterization.
      METHODS: Fractal dimension images are generated based on the radio frequency
      signals obtained using mechanically rotating 40 MHz intravascular ultrasound
      catheter (Atlantis SR Plus, Boston Scientific, USA) and compared with the
      corresponding correlation images. CONCLUSION: An inverse relation between the
      fractal dimension images and the correlation images was revealed indicating that
      the hard or slow moving tissues in the correlation image usually have low fractal
      dimension and vice-versa. Thus, the present study suggests that fractal dimension
      images may be used as a feature for intravascular ultrasound tissue
      characterization and present better resolution then the correlation images.

PMID- 18078667
TI  - Brightness discrimination in the harbor seal (Phoca vitulina).
AB  - The brightness discrimination ability of a male harbor seal was investigated at
      an ambient illumination of 0.9lx. The visual stimuli consisted of circular gray
      discs that were presented on a black background on a TFT monitor. Eight standard
      intensities were tested against sets of lower comparison intensities. In
      accordance with Weber's law we observed a constant gain of the just noticeable
      intensity difference with increasing intensity of the standard stimulus. The
      calculated Weber fraction is 0.14. This result indicates that the brightness
      discrimination ability of the harbor seal is comparable to that of humans.

PMID- 18078668
TI  - Formation of adducts in the reaction of glyoxal with 2'-deoxyguanosine and with
      calf thymus DNA.
AB  - The reactions of glyoxal with 2'-deoxyguanosine and calf thymus single- and
      double-stranded DNA in aqueous buffered solutions at physiological conditions
      resulted in the formation of two previously undetected adducts in addition to the
      known reaction product 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7-trihydro
      6,7-dihydroxyimidazo[1,2-a]purine-9-one (Gx-dG). The adducts were isolated and
      purified by reversed-phase liquid chromatography and structurally characterised
      by UV absorbance, mass spectrometry, (1)H and (13)C NMR spectroscopy. The
      hitherto unknown adducts were identified as: 5-carboxymethyl-3-(2'-deoxy-beta-D
      erythro-pentofuranosyl)-5,6,7-trihydro-6,7-dihydroxyimidazo[1,2-a]purine-9-one
      (Gx(2)-dG) and N(2)-(carboxymethyl)-9-(2'-deoxy-beta-D-erythro-pentofuranosyl)
      purin-6(9H)-one (Gx(1)-dG). Both adducts were shown to arise from Gx-dG. Gx-dG
      and Gx(2)-dG were found to be unstable and partly transformed to Gx(1)-dG, which
      is a stable adduct and seems to be the end-product of the glyoxal reaction with
      2'-deoxyguanosine. All adducts formed in the reaction of glyoxal with 2'
      deoxyguanosine were observed in calf thymus DNA. Also in DNA, Gx(1)-dG was the
      only stable adduct. The transformation of Gx-dG to Gx(1)-dG seemed to take place
      in single-stranded DNA and therefore, Gx(1)-dG may be a potentially reliable
      biomarker for glyoxal exposure and may be involved in the genotoxic properties of
      the compound.

PMID- 18078669
TI  - Solar TiO2-assisted photocatalytic degradation of IGCC power station effluents
      using a Fresnel lens.
AB  - The heterogeneous TiO2 assisted photocatalytic degradation of wastewater from a
      thermoelectric power station under concentrated solar light irradiation using a
      Fresnel lens has been studied. The efficiency of photocatalytic degradation was
      determined from the analysis of cyanide and formate removal. Firstly, the
      influence of the initial concentration of H2O2 and TiO2 on the degradation
      kinetics of cyanides and formates was studied based on a factorial experimental
      design. Experimental kinetic constants were fitted using neural networks. Results
      showed that the photocatalytic process was effective for cyanides destruction
      (mainly following a molecular mechanism), whereas most of formates (degraded
      mainly via a radical path) remained unaffected. Finally, to improve formates
      degradation, the effect of lowering pH on their degradation rate was evaluated
      after complete cyanide destruction. The photooxidation efficiency of formates
      reaches a maximum at pH around 5-6. Above pH 6, formate anion is subjected to
      electrostatic repulsion with the negative surface of TiO2. At pH<4.5, formate
      adsorption and photon absorption are reduced due to some catalyst agglomeration.

PMID- 18078671
TI  - Collaborative discourse facilitates efficient communication and new learning in
      amnesia.
AB  - In previous work we reported robust collaborative learning for referential labels
      in patients with hippocampal amnesia, resulting in increasingly rapid and
      economical communication or "common ground" with their partners [Duff, M. C.,
      Hengst, J., Tranel, D., & Cohen, N. J. (2006). Development of shared information
      in communication despite hippocampal amnesia. Nature Neuroscience, 9(1), 140
      146]. The current paper reports the results of discourse analysis, describing the
      communicative resources and practices used in extended, repeated collaborative
      interactions, as partners successfully referenced the target cards, managed the
      task itself, and engaged in non-task talk. Although amnesic pairs showed a normal
      rate of reduction across trials in the number of words and time-to-completion,
      their communicative effort was higher overall, particularly the discourse
      associated with task management, they exhibited a general lack of flexibility in
      their referential expressions, and they showed a number of striking differences
      in use of personal and communal knowledge and of multiple perspectives. The
      interactive sessions provided a potent learning environment, but also a very
      challenging task in the face of memory impairment. The results give insight into
      the acquisition of common ground and the manner in which amnesic patients
      accommodate their memory deficits during real-world interactions, and they have
      significant implications for memory intervention.

PMID- 18078672
TI  - Alpha-ketoglutarate and N-acetyl cysteine protect PC12 cells from cyanide-induced
      cytotoxicity and altered energy metabolism.
AB  - Cyanide is a rapidly acting neurotoxin that inhibits cellular respiration and
      energy metabolism leading to histotoxic hypoxia. This results in the dissipation
      of mitochondrial membrane potential (MMP) accompanied by decreased cellular ATP
      content which in turn is responsible for increased levels of intracellular
      calcium ions ([Ca(2+)](i)) and total lactic acid content of the cells. Rat
      pheochromocytoma (PC12) cells possess much of the biochemical machinery
      associated with synaptic neurons. In the present study, we evaluated the
      cytoprotective effects of alpha-ketoglutarate (A-KG) and N-acetylcysteine (NAC)
      against cyanide-induced cytotoxicity and altered energy metabolism in PC12 cells.
      Cyanide-antagonism by A-KG is attributed to cyanohydrin formation whereas NAC is
      known for its antioxidant properties. Data on leakage of intracellular lactate
      dehydrogenase and mitochondrial function (MTT assay) revealed that simultaneous
      treatment of A-KG (0.5 mM) and NAC (0.25 mM) significantly prevented the
      cytotoxicity of cyanide. Also, cellular ATP content was found to improve,
      followed by restoration of MMP, intracellular calcium [Ca(2+)](i) and lactic acid
      levels. Treatment with A-KG and NAC also attenuated the levels of peroxides
      generated by cyanide. The study indicates that combined administration of A-KG
      and NAC protected the cyanide-challenged PC12 cells by resolving the altered
      energy metabolism. The results have implications in the development of new
      treatment regimen for cyanide poisoning.

PMID- 18078673
TI  - Biological effect of mono- and dinuclear alkylamine platinum(II) compounds on
      human lymphoma cells.
AB  - The effects of the mononuclear chloro[meso-1,2-bis(4
      fluorophenyl)ethylenediamine][hexylamine]platinum(II) chloride HACl and the
      dinuclear di[meso-1,2-bis(4-fluorophenyl)ethylenediamine]dichloro(mu-1,n
      diaminoalkane-N:N')diplatinum(II)dichloride complexes DAHCl (alkane:hexane),
      DANCl (alkane:nonane) and DADCl (alkane:dodecane) with different alkyl chain
      length (n) were investigated on non-Hodgkin's lymphoma (NHL) and chronic myeloid
      leukemia (CML) cell lines. All compounds showed an antiproliferative effect on
      the NHL cell lines RAJI and U-937 accompanied in the case of DANCl, DAHCl, HACl
      and cisplatin by an increase in apoptosis. The growth of another NHL (JEKO-1) and
      one CML cell line (K-562) was decreased only by cisplatin. In contrast to HACl,
      DAHCl, DANCl and cisplatin, DADCl induced necrosis, suggesting toxicity because
      cell viability decreased. Similar effects were observed when bone marrow-derived
      lymphoma cells from a patient with high-grade B-NHL were incubated with the
      platinum complexes.

PMID- 18078670
TI  - Reduced mitochondrial SOD displays mortality characteristics reminiscent of
      natural aging.
AB  - Manganese superoxide dismutase (MnSOD or SOD2) is a key mitochondrial enzymatic
      antioxidant. Arguably the most striking phenotype associated with complete loss
      of SOD2 in flies and mice is shortened life span. To further explore the role of
      SOD2 in protecting animals from aging and age-associated pathology, we generated
      a unique collection of Drosophila mutants that progressively reduce SOD2
      expression and function. Mitochondrial aconitase activity was substantially
      reduced in the Sod2 mutants, suggesting that SOD2 normally ensures the functional
      capacity of mitochondria. Flies with severe reductions in SOD2 expression
      exhibited accelerated senescence of olfactory behavior as well as precocious
      neurodegeneration and DNA strand breakage in neurons. Furthermore, life span was
      progressively shortened and age-dependent mortality was increased in conjunction
      with reduced SOD2 expression, while initial mortality and developmental viability
      were unaffected. Interestingly, life span and age-dependent mortality varied
      exponentially with SOD2 activity, indicating that there might normally be a
      surplus of this enzyme for protecting animals from premature death. Our data
      support a model in which disruption of the protective effects of SOD2 on
      mitochondria manifests as profound changes in behavioral and demographic aging as
      well as exacerbated age-related pathology in the nervous system.

PMID- 18078674
TI  - Prevalence of tympanometric alterations in children with chronic sinusitis.
AB  - OBJECTIVE: Due to its anatomical and functional connections, middle ear disorders
      frequently occur in sinusitis. Its prevalence, however, is likely to be
      underestimated. We evaluated the prevalence of middle ear dysfunction, as
      assessed by tympanometry, in children with chronic sinusitis in a large group of
      patients with chronic respiratory symptoms, and its possible relationship with
      respiratory allergy. METHODS: From a population of 1,810 children with
      respiratory symptoms referred to our Pediatric Allergy center, subjects with
      chronic sinusitis diagnosed by clinical criteria were selected. Children
      underwent testing of middle ear function by tympanometry and of allergy by skin
      tests with environmental allergens. Patients were divided into three groups
      according to age. RESULTS: Two hundred and eighty-eight children (15.9%) had
      clinical diagnosis of chronic sinusitis according to the established criteria.
      Twenty-four patients were in group 1, 220 in group 2, and 44 in group 3. Altered
      middle ear pressure was found in 76.4% of patients, with a significantly higher
      rate of altered tympanograms in younger children (p<0.001). A positive skin prick
      test was found in 29.9% of children, with a significantly higher rate of
      positivity in older children (p=0.01). CONCLUSIONS: The decrease with age in the
      rate of tympanometric alterations is likely to be associated to the anatomic
      development of the upper airways, while the presence of atopy does not seem to
      play a role in their occurrence.

PMID- 18078675
TI  - A multiplex real-time RT-PCR for detection and identification of influenza virus
      types A and B and subtypes H5 and N1.
AB  - A multiplex real-time RT-PCR method for the simultaneous detection of influenza
      virus types A and B and identification of subtypes H5 and N1 in a single tube is
      described. The method was developed with four sets of primers and probes which
      were specific to influenza virus (sub)types A, B, H5, and N1, and evaluated by
      using a total of 40 influenza virus reference strains, including 17 avian
      influenza A (12 H5N1, 1 H1N1, 1 H3N2, 1 H4N6, 1 H7N3, and 1 H9N2), 18 human
      influenza A (11 H3N2, 6 H1N1 and 1 H5N1) and 5 influenza B viruses. The method
      exhibited a high specificity and sensitivity of approximately 10(1)
      10(2)copies/microl for each (sub)type and a high reproducibility with intra- and
      inter-assay CV from 0.13 to 4.24%. In an analysis of 189 clinical samples from
      patients during the year 2004 and 2005, the method identified 81 positive samples
      (42.9%) and identified simultaneously 14 type B samples and 11 subtype N1
      samples, in comparison only 46 positive samples (24.3%) identified by the
      conventional culturing method. The method would be a useful molecular diagnostic
      tool for large-scale screening of clinical samples for influenza virus.

PMID- 18078676
TI  - Comparison of the efficacy of thymosin alpha-1 and interferon alpha in the
      treatment of chronic hepatitis B: a meta-analysis.
AB  - Chronic hepatitis B virus (HBV) infection is a serious problem because of its
      worldwide distribution and possible adverse sequelae, such as cirrhosis and
      hepatocellular carcinoma. Thymosin alpha-1 (Talpha1) is an immune modifier that
      has been shown to be effective for chronic hepatitis B (CHB) in some trials. But
      the trials comparing Talpha1 vs. interferon alpha (IFNalpha) treatment in CHB
      have been small and the results have been inconsistent. So we conducted a meta
      analysis to compare the efficacy of Talpha1 and IFNalpha in the treatment of CHB.
      Generally, four randomized controlled trials including 199 CHB patients who
      received Talpha1 or IFNalpha treatment were identified through MEDLINE and EMBASE
      online search. Virological (for hepatitis B e antigen (HBeAg) positive patients,
      loss of HBV DNA and HBeAg; for HBeAg negative patients, loss of HBV DNA),
      biochemical (normalization of transaminases) and complete responses (fulfill
      criteria of biochemical and virological response simultaneously) were analyzed
      using the intention-to-treat method. The odds ratio (OR) was used to measure the
      magnitude of the efficacy. The ORs (95% confidence interval) of the virological
      response, biochemical response and complete response of Talpha1 over IFNalpha at
      the end of 6 months treatment were 0.62 (0.35, 1.10), 0.60 (0.34, 1.05) and 0.54
      (0.30, 0.97), respectively. The ORs (95% confidence interval) of the virological
      response, biochemical response and complete response of Talpha1 over IFNalpha at
      the end of follow-up (6 months post-treatment) were 3.71 (2.05, 6.71), 3.12
      (1.74, 5.62) and 2.69 (1.47, 4.91), respectively. These data showed that compared
      with IFNalpha, the benefit of Talpha1 was not immediately significant at the end
      of therapy, but virological, biochemical and complete response had a tendency to
      increase or accumulate gradually after the therapy. For three of the four trials
      that studied HBeAg-negative patients, the results are mostly applicable to HBeAg
      negative CHB.

PMID- 18078677
TI  - Glucuronidation and sulfonation, in vitro, of the major endocrine-active
      metabolites of methoxychlor in the channel catfish, Ictalurus punctatus, and
      induction following treatment with 3-methylcholanthrene.
AB  - The organochlorine pesticide, methoxychlor (MXC), is metabolized in animals to
      phenolic mono- and bis-demethylated metabolites (OH-MXC and HPTE, respectively)
      that interact with estrogen receptors and may be endocrine disruptors. The phase
      II detoxication of these compounds will influence the duration of action of the
      estrogenic metabolites, but has not been investigated extensively. In this study,
      the glucuronidation and sulfonation of OH-MXC and HPTE were investigated in
      subcellular fractions of liver and intestine from untreated, MXC-treated and 3
      methylcholanthrene (3-MC)-treated channel catfish, Ictalurus punctatus. MXC
      treated fish were given i.p. injections of 2mg MXC/kg daily for 6 days and
      sacrificed 24h after the last dose. The 3-MC treatment was a single 10mg/kg i.p.
      dose 5 days prior to sacrifice. In hepatic microsomes from control fish, the
      V(max) value (mean+/-S.D., n=4) for glucuronidation of OH-MXC was 270+/
      50pmol/min/mg protein, higher than found for HPTE (110+/-20pmol/min/mg protein).
      For each substrate, the V(max) values observed in intestinal microsomes were
      approximately twice those found in the liver. The K(m) values for OH-MXC and HPTE
      glucuronidation in control liver were not significantly different and were 0.32+/
      0.04mM for OH-MXC and 0.26+/-0.06mM for HPTE. The K(m) for the co-substrate,
      UDPGA, was higher in liver (0.28+/-0.09mM) than intestine (0.04+/-0.02mM).
      Treatment with 3-MC but not MXC increased the V(max) for glucuronidation in liver
      and intestine. Glucuronidation was a more efficient pathway than sulfonation for
      both substrates, in both tissues. The V(max) values for sulfonation of OH-MXC and
      HPTE, respectively, in liver cytosol were 7+/-3 and 17+/-4pmol/min/mg protein and
      in intestinal cytosol were 13+/-3 and 30+/-5pmol/min/mg protein. Treatment with 3
      MC but not MXC increased rates of sulfonation of OH-MXC and HPTE and the model
      substrate, 3-hydroxy-benzo(a)pyrene in both intestine and liver. Comparison of
      the kinetics of the conjugation pathways with those published for the
      demethylation of MXC showed that formation of the endocrine-active metabolites
      was more efficient than either conjugation pathway. Residues of OH-MXC and HPTE
      were detected in extracts of liver microsomes from MXC-treated fish. This work
      showed that although OH-MXC and HPTE could be eliminated by glucuronidation and
      sulfonation, the phase II pathways were less efficient than the phase I pathway
      leading to formation of these endocrine-active metabolites.

PMID- 18078678
TI  - Relationships between ground reaction force parameters during a sit-to-stand
      movement and physical activity and falling risk of the elderly and a comparison
      of the movement characteristics between the young and the elderly.
AB  - This study aimed to examine the relationships between ground reaction force
      during a sit-to-stand (STS) movement and physical activity and falling risk of
      the elderly and the difference of the movement characteristics between the young
      and the elderly. Sixty elderly females who can achieve a STS movement by
      themselves and 30 healthy young females were measured for ground reaction force
      during STS movement from a chair, adjusted for lower leg length height. The
      elderly's physical activity and falling risk were also assessed. Physical
      activity and falling risk significantly correlated with parameters on force
      exertion during hip lift-off and knee-hip joint extension phases (|r|=0.26-0.41).
      Significant differences were found in ground reaction force parameters of all
      phases between the young and the elderly and STS movement of the elderly was
      suggested to result in poor force exertion and slowing down. The above tendency
      was noticeable in the hip lift-off and knee-hip joint extension phases. In
      conclusion, force exertion in hip lift-off and knee-hip joint extension phases of
      STS movement is related to physical activity and falling risk in the elderly.
      These phases may be useful to evaluate the elderly's physical activity and
      falling risk.

PMID- 18078679
TI  - Alternative pig liver esterase (APLE) - cloning, identification and functional
      expression in Pichia pastoris of a versatile new biocatalyst.
AB  - Isolated from pig liver as a crude, inhomogeneous enzyme fraction, pig liver
      esterase (PLE) was found to metabolize a wide range of substrates; often in a
      highly stereoselective manner. This crude esterase preparation, however, contains
      several iso-enzymes at proportions varying from batch to batch. Racemic methyl
      (4E)-5-chloro-2-isopropyl-4-pentenoate is cleaved enantioselectively by crude
      PLE, but not by recombinantly expressed gamma-isoform of PLE. Concluding that
      another PLE iso-enzyme must carry the relevant activity, we cloned and sequenced
      cDNAs of several PLE isoforms and functionally expressed them in Pichia pastoris.
      One novel isoform termed alternative pig liver esterase (APLE) was found to
      hydrolyze methyl-(2R,4E)-5-chloro-2-isopropyl-4-pentenoate in a highly
      stereoselective manner (E>200). When heterologously expressed and directed for
      secretion in P. pastoris, APLE was found to be localized in the periplasm. The
      presence or absence of a putative C-terminal ER retention signal did neither
      influence functional expression nor cellular localization. The recombinant
      enzyme, purified by ion exchange chromatography, had a specific activity of 36U
      (mg protein)(-1) towards racemic methyl-(4E)-5-chloro-2-isopropyl-4-pentenoate.

PMID- 18078680
TI  - The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic
      hepatitis C infection.
AB  - BACKGROUND/AIMS: The chemokine receptor CX3CR1 and its specific ligand
      fractalkine (CX3CL1) are known to modulate inflammatory and fibroproliferative
      diseases. Here we investigate the role of CX3CR1/fractalkine in HCV-induced liver
      fibrosis. METHODS: A genotype analysis of CX3CR1 variants was performed in 211
      HCV-infected patients. Hepatic expression of CX3CR1 was studied in HCV-infected
      livers and isolated liver cell populations by RT-PCR and immunohistochemistry.
      The effects of fractalkine on mRNA expression of profibrogenic genes were
      determined in isolated hepatic stellate cells (HSC) and CX3CR1 genotypes were
      related to intrahepatic TIMP-1 mRNA levels. RESULTS: The intrahepatic mRNA
      expression of CX3CR1 correlates with the stage of HCV-induced liver fibrosis
      (P=0.03). The CX3CR1 coding variant V249I is associated with advanced liver
      fibrosis, independent of the T280M variant (P=0.009). CX3CR1 is present on
      primary HSC and fractalkine leads to a suppression of tissue inhibitor of
      metalloproteinase (TIMP)-1 mRNA in HSC (P=0.03). Furthermore, CX3CR1 genotypes
      are associated with TIMP-1 mRNA expression in HCV-infected liver (P=0.03).
      CONCLUSIONS: The results identify the fractalkine receptor CX3CR1 as
      susceptibility a gene for hepatic fibrosis in HCV infection. The modulation of
      TIMP-1 expression by fractalkine and CX3CR1 genotypes provides functional support
      for the observed genotype-phenotype association.

PMID- 18078681
TI  - A bed too far. The implementation of freedom of choice policy in the NHS.
AB  - Freedom of hospital choice has become a popular policy among the European public
      health services to ensure better patient rights, reduce waiting times and improve
      efficiency and quality in public hospitals. The English National Health Service
      has recently adopted this policy. This organisation needs to introduce important
      reforms in order to implement this policy, in particular in the information that
      it provides to patients. This paper presents the Andalusian Health Service (SAS)
      initiative in the disclosure of information, based on patient surveys, so it can
      be understood by patients. Andalusia implemented a freedom of choice policy 10
      years ago. This paper also studies how SAS hospitals are scored by patients and
      how the quality of hospitals may affect their choice. Regression analyses
      indicate that two hospital dimensions, a 'human dimension' and a 'facilities
      dimension', significantly explain how patients assess the quality of the
      Andalusian hospitals. Nonetheless, these two dimensions do not explain the
      reputation of the hospitals, a main aspect when choosing a hospital, to the same
      extent. The lessons provided by looking at the SAS experience may give an
      insightful knowledge on whether patients in England will finally opt for the best
      hospitals.

PMID- 18078682
TI  - How surgeons can find information online?

PMID- 18078683
TI  - Biomedical research ethics: an Islamic view part II.
AB  - In part I of this article I discussed why Islam rejects secularization and this
      is not because the ethical principles embedded in Islam's teachings are archaic
      and out of touch with current realities. In addition, I pointed out the agreement
      between general broad principles of research ethics and Islamic teachings
      concerning life; which showed clearly that Islam has addressed the regulation of
      ethics in research more than 14 centuries ago. In this part, I will address two
      controversial issues concerning women's rights and age of consent for children as
      possible research subjects in a Muslim community.

PMID- 18078684
TI  - Sensory motor systems of artificial and natural hands.
AB  - The surgeon Ambroise Pare designed an anthropomorphic hand for wounded soldiers
      in the 16th century. Since that time, there have been advances in technology
      through the use of computer-aided design, modern materials, electronic
      controllers and sensors to realise artificial hands which have good functionality
      and reliability. Data from touch, object slip, finger position and temperature
      sensors, mounted in the fingers and on the palm, can be used in feedback loops to
      automatically hold objects. A study of the natural neuromuscular systems reveals
      a complexity which can only in part be realised today with technology. Highlights
      of the parallels and differences between natural and artificial hands are
      discussed with reference to the Southampton Hand. The anatomical structure of
      parts of the natural systems can be made artificially such as the antagonist
      muscles using tendons. Theses solutions look promising as they are based on the
      natural form but in practice lack the desired physical specification. However,
      concepts of the lower spinal loops can be mimicked in principle. Some future
      devices will require greater skills from the surgeon to create the interface
      between the natural system and an artificial device. Such developments may offer
      a more natural control with ease of use for the limb deficient person.

PMID- 18078685
TI  - Abdominal actinomycosis.
AB  - Abdominal actinomycosis has been recognised for over 150 years yet remains
      largely unknown to most clinicians. It's varied presentations are usually
      considered to represent malignancy rather than an infective process - and was
      once described as 'the most misdiagnosed disease'. Actinomyces are gram positive
      bacilli of the Actinomycetales genus, and A. israelii is responsible for the
      majority of human disease. They are normal commensal inhabitants of the human
      bronchial and gastrointestinal tracts and seem to only cause pathological
      infection after preceding mucosal breakdown. Patients who have undergone
      appendicectomy, have had a missed perforated appendicitis or women with a history
      of intrauterine contraceptive device use are at an increased risk. Florid abscess
      formation with fistulation, abundant granulation and dense surrounding fibrosis
      are common. Diagnosis prior to, or even during, surgery is rare and the findings
      are usually mistaken for acute inflammatory pathologies or malignancy. The
      treatment of choice is prolonged antibiotic therapy, usually with penicillin to
      which the organisms remain exquisitely sensitive, although delayed recurrence is
      possible. This review outlines the historical background of actinomyceal
      infection and considers the epidemiology, pathophysiology and clinical features
      of abdominal actinomycosis.

PMID- 18078686
TI  - Helokinestatin: a new bradykinin B2 receptor antagonist decapeptide from lizard
      venom.
AB  - Synthetic bradykinin antagonist peptides/peptoids have been powerful tools for
      delineating the roles of kinins in both normal physiology and in pathological
      states. Here, we report the identification of a novel, naturally occurring
      bradykinin B2 receptor antagonist peptide, helokinestatin, isolated and
      structurally characterized from the venoms of helodermatid lizards-the Gila
      monster (Heloderma suspectum) and the Mexican beaded lizard (Heloderma horridum).
      The primary structure of the peptide was established by a combination of
      microsequencing and mass spectroscopy as Gly-Pro-Pro-Tyr-Gln-Pro-Leu-Val-Pro-Arg
      (Mr 1122.62). A synthetic replicate of helokinestatin was found to inhibit
      bradykinin-induced vasorelaxation of phenylephrine pre-constricted rat tail
      artery smooth muscle, mediated by the B2 receptor sub-type, in a dose-dependent
      manner. Natural selection, that generates functional optimization of predatory
      reptile venom peptides, can potentially provide new insights for drug lead design
      or for normal physiological or pathophysiological processes.

PMID- 18078687
TI  - Alkaline phosphatase: keeping the peace at the gut epithelial surface.
AB  - Vertebrate intestinal surfaces are in constant contact with a vast consortium of
      commensal bacteria. To preserve mutually beneficial host-microbial relationships,
      gut epithelia have evolved strategies to limit the proinflammatory potential of
      resident gut microbes. In this issue of Cell Host & Microbe, Bates and colleagues
      report that intestinal alkaline phosphatase, whose expression is induced during
      establishment of the microbiota, dephosphorylates lipopolysaccharide and promotes
      mucosal tolerance to commensal bacteria in zebrafish.

PMID- 18078688
TI  - Ub surprised: viral ovarian tumor domain proteases remove ubiquitin and ISG15
      conjugates.
AB  - Conjugation of ubiquitin regulates multiple pathways, including the signaling
      cascades leading to antiviral immunity. Similarly, the ubiquitin-like peptide
      ISG15 mediates the antiviral response to certain viruses. In this issue of Cell
      Host & Microbe, Frias-Staheli and colleagues demonstrate that research on viral
      proteases of certain nairoviruses and arteriviruses reveals the presence of
      ovarian tumor domain-containing sequences that act as general deubiquitinases and
      deISGylases and increase viral replication by inhibiting the antiviral response
      mediated by ISG15.

PMID- 18078689
TI  - Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents
      inflammation in zebrafish in response to the gut microbiota.
AB  - Vertebrates harbor abundant lipopolysaccharide (LPS) in their gut microbiota.
      Alkaline phosphatases can dephosphorylate and detoxify the endotoxin component of
      LPS. Here, we show that expression of the zebrafish intestinal alkaline
      phosphatase (Iap), localized to the intestinal lumen brush border, is induced
      during establishment of the gut microbiota. Iap-deficient zebrafish are
      hypersensitive to LPS toxicity and exhibit the excessive intestinal neutrophil
      influx characteristic of wild-type zebrafish exposed to LPS. Both of these Iap
      mutant phenotypes are dependent on Myd88 and Tumor Necrosis Factor Receptor
      (Tnfr), proteins also involved in LPS sensitivity in mammals. When reared germ
      free, the intestines of Iap-deficient zebrafish are devoid of neutrophils.
      Together, these findings demonstrate that the endogenous microbiota establish the
      normal homeostatic level of neutrophils in the zebrafish intestine through a
      process involving Iap, Myd88, and Tnfr. Thus, by preventing inflammatory
      responses, Iap plays a crucial role in promoting mucosal tolerance to resident
      gut bacteria.

PMID- 18078690
TI  - The enteropathogenic E. coli effector EspB facilitates microvillus effacing and
      antiphagocytosis by inhibiting myosin function.
AB  - Enteropathogenic Escherichia coli (EPEC) destroys intestinal microvilli and
      suppresses phagocytosis by injecting effectors into infected cells through a type
      III secretion system (TTSS). EspB, a component of the TTSS, is also injected into
      the cytoplasm of host cells. However, the physiological functions of EspB within
      the host cell cytoplasm remain unclear. We show that EspB binds to myosins, which
      are a superfamily of proteins that interact with actin filaments and mediate
      essential cellular processes, including microvillus formation and phagocytosis.
      EspB inhibits the interaction of myosins with actin, and an EspB mutant that
      lacks the myosin-binding region maintained its TTSS function but could not induce
      microvillus effacing or suppress phagocytosis. Moreover, the myosin-binding
      region of EspB is essential for Citrobacter rodentium, an EPEC-related murine
      pathogen, to efficiently infect mice. These results suggest that EspB inhibits
      myosin functions and thereby facilitates efficient infection by EPEC.

PMID- 18078691
TI  - Host glycoprotein Gp96 and scavenger receptor SREC interact with PorB of
      disseminating Neisseria gonorrhoeae in an epithelial invasion pathway.
AB  - Neisseria gonorrhoeae expresses numerous surface proteins that mediate bacterial
      adherence and invasion during infection. Gonococci expressing serotype A of the
      major outer membrane porin PorB (PorB(IA)) are frequently isolated from patients
      with severe disseminating infections. PorB(IA) triggers efficient adherence and
      invasion under low phosphate conditions mimicking systemic bloodstream
      infections. Here, we identify the human heat shock glycoprotein Gp96 and the
      scavenger receptor SREC as PorB(IA)-specific receptors. Gonococci expressing
      PorB(IA), but not those expressing PorB serotype B instead, bind to purified
      native or recombinant Gp96. Depletion of Gp96 from host cells prevented adherence
      but significantly triggered gonococcal invasion. Furthermore, such invasion was
      blocked by chemical inhibitors of scavenger receptors, and we identified SREC as
      the scavenger receptor involved in PorB(IA)-dependent invasion. Thus, we
      establish Gp96 as an anti-invasion factor and SRECs as receptors mediating host
      cell entry of highly invasive disseminating gonococci.

PMID- 18078692
TI  - Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15
      dependent innate immune responses.
AB  - Ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15) reversibly
      conjugate to proteins and mediate important innate antiviral responses. The
      ovarian tumor (OTU) domain represents a superfamily of predicted proteases found
      in eukaryotic, bacterial, and viral proteins, some of which have Ub-deconjugating
      activity. We show that the OTU domain-containing proteases from nairoviruses and
      arteriviruses, two unrelated groups of RNA viruses, hydrolyze Ub and ISG15 from
      cellular target proteins. This broad activity contrasts with the target
      specificity of known mammalian OTU domain-containing proteins. Expression of a
      viral OTU domain-containing protein antagonizes the antiviral effects of ISG15
      and enhances susceptibility to Sindbis virus infection in vivo. We also show that
      viral OTU domain-containing proteases inhibit NF-kappaB-dependent signaling.
      Thus, the deconjugating activity of viral OTU proteases represents a unique viral
      strategy to inhibit Ub- and ISG15-dependent antiviral pathways.

PMID- 18078694
TI  - Nonimmunodominant regions are effective as building blocks in a streptococcal
      fusion protein vaccine.
AB  - Identification of antigens that elicit protective immunity is essential for
      effective vaccine development. We investigated the related surface proteins of
      group B Streptococcus, Rib and alpha, as potential vaccine candidates.
      Paradoxically, nonimmunodominant regions proved to be of particular interest as
      vaccine components. Mouse antibodies elicited by Rib and alpha were directed
      almost exclusively against the C-terminal repeats and not against the N-terminal
      regions. However, a fusion protein derived from the nonimmunodominant N-terminal
      regions of Rib and alpha was much more immunogenic than one derived from the
      repeats and was immunogenic even without adjuvant. Moreover, antibodies to the N
      terminal fusion protein protected against infection and inhibited bacterial
      invasion of epithelial cells. Similarly, the N-terminal region of Streptococcus
      pyogenes M22 protein, which is targeted by opsonic antibodies, is
      nonimmunodominant. These data indicate that nonimmunodominant regions of
      bacterial antigens could be valuable for vaccine development.

PMID- 18078693
TI  - Complement protein C1q inhibits antibody-dependent enhancement of flavivirus
      infection in an IgG subclass-specific manner.
AB  - Severe dengue virus infection can occur in humans with pre-existing antibodies
      against the virus. This observation led to the hypothesis that a subneutralizing
      antibody level in vivo can increase viral burden and cause more severe disease.
      Indeed, antibody-dependent enhancement of infection (ADE) in vitro has been
      described for multiple viruses, including the flaviviruses dengue virus and West
      Nile virus. Here, we demonstrate that the complement component C1q restricts ADE
      by anti-flavivirus IgG antibodies in an IgG subclass-specific manner in cell
      culture and in mice. IgG subclasses that avidly bind C1q induced minimal ADE in
      the presence of C1q. These findings add a layer of complexity for the analysis of
      humoral immunity and flavivirus infection.

PMID- 18078695
TI  - APOE, ACT and CHRNA7 genes in the conversion from amnestic mild cognitive
      impairment to Alzheimer's disease.
AB  - We have investigated whether the -86 C/T promoter polymorphism in CHRNA7 gene,
      the signal peptide polymorphism of the alpha1-antichymotripsin (ACT) gene or the
      APOE genotype are associated with an increased risk of mild cognitive impairment
      (MCI) or affect the risk of evolution to Alzheimer's disease (AD). We have
      followed up 89 patients with initial diagnoses of amnestic MCI for 49 months.
      Patients were separated into three groups: 27 subjects who remained with MCI, 40
      that converted to AD before 20 months and 22 that converted to AD after. To
      assess the risk associated to each genotype a control group (n=90) without
      cognitive impairment was included. APOE4 allele was associated with an increased
      risk of MCI (OR: 6.04, 95% CI: 2.76-3.23; p<0.001) but did not have an effect on
      the probability of evolving AD. ACT or CHRNA7 genotypes were not associated with
      MCI but both appear to modify the risk of progression to dementia in opposing
      manners: ACT polymorphism increasing the risk to evolve to AD before 20 months
      (HR=2.03; 95% CI: 1-4.6; p=0.06) and CHRNA7 polymorphism protecting from
      evolution to dementia. Cox regression model demonstrated that ACT genotype
      confers a higher risk of rapid evolution to dementia than age or years of
      schooling. We conclude that APOE is a risk gene for amnestic MCI and that ACT and
      CHRNA7 may act in these patients as modifier genes for the time of progression to
      AD.

PMID- 18078696
TI  - The adaptive response of periodontal ligament to orthodontic force loading - a
      combined biomechanical and biological study.
AB  - BACKGROUND: The studies on biomechanics of orthodontic tooth movement (OTM) are
      mainly performed at analytical, tissue and cellular levels. The prime aim of this
      study was to elucidate the periodontal response to orthodontic force loading by
      integrating biomechanical and biological approaches. METHODS: We designed and
      conducted a multilevel study consisting of three parts. (1) At the
      analytical/theoretical level, 3D finite element (FE) method was used to analyze
      stress distribution and changing during OTM. (2) At the tissue level, we explored
      the effects of tensile and compressive forces on the expressions of Type I
      collagen, matrix metalloproteinases Type I (MMP-1) and tissue inhibitor of
      metalloproteinase Type I (TIMP-1) in rat's periodontal ligament (PDL) in vivo.
      (3) At the cellular level, we studied the effects of variant strain patterns and
      magnitudes on functional expression of rat's osteoblasts in vitro. FINDINGS: (1)
      In the 3D FE model, the canine tipping and bodily movements showed different ways
      in stress distribution and degeneration. However, in both tooth movement
      modalities, tensile zones and compressive zones had similar stress distribution
      pattern. (2) Tensile and compressive forces imposed different effects on the
      expressions of Type I collagen, MMP-1 and TIMP-1 in PDL, with Type I collagen and
      TIMP-1being increased significantly in the tensile zones and MMP-1 being
      increased significantly in both zones. (3) Differences in strain pattern (dynamic
      vs. static) and magnitude (light vs. heavy) resulted in different levels of
      osteoblast's functional expression indicated by alkaline phosphatase (ALP) and
      osteocalcin (OC). It was found that dynamic loading was more effective for ALP
      expression whilst static loading was more effective for OC secretion and 3kPa
      strain force in vitro was optimal for the both. INTERPRETATION: It is suggested
      that there may exist an optimal force system in both magnitude and pattern of
      loading that could induce efficient OTM.

PMID- 18078697
TI  - Preservation of periarticular cancellous morphology and mechanical stiffness in
      post-traumatic experimental osteoarthritis by antiresorptive therapy.
AB  - BACKGROUND: Bone changes in experimental post-traumatic osteoarthritis occur
      early after transection of the anterior cruciate. The purpose of this study was
      to determine whether antiresorptive bisphosphonate therapy could slow or arrest
      the periarticular bone architecture and mechanical properties in a post-traumatic
      model of knee osteoarthritis. METHODS: Skeletally mature, female New Zealand
      white rabbits were assigned to three groups (N=8/group). In two groups, anterior
      cruciate ligament transection was performed and half were left untreated, and the
      other half dosed with risedronate (0.01 mg/kg s.c. daily) for a six week period.
      A third group included age-matched normal controls. At the end of the six week
      period, all rabbits were euthanized and the femur was scanned by micro-computed
      tomography to assess morphology and density. Specimen-specific finite element
      analyses quantified the periarticular bone architecture and mechanical
      properties. FINDINGS: The untreated transected group had reduced bone volume
      ratio and mechanical properties compared to the controls (P<0.05) and risedronate
      treated transected animals (P<0.02), suggesting bone conservation. Changes in
      bone volume ratio and mechanical properties of the risedronate-treated transected
      animals compared to the controls were not detected, indicating that risedronate
      did not improve these properties relative to the normal controls. The untreated
      transected group had reduced apparent cancellous bone mineral density and
      cortical thickness compared to transected animals treated with risedronate
      (P<0.05). INTERPRETATION: Bisphosphonate therapy altered the short-term
      progression of periarticular bone changes including micro-structure and
      mechanical integrity by slowing early-stage changes to the micro-architecture.
      These changes following joint trauma may impact the long-term outcome of post
      traumatic osteoarthritis.

PMID- 18078698
TI  - Mapping aerial metal deposition in metropolitan areas from tree bark: a case
      study in Sheffield, England.
AB  - We investigated the use of metals accumulated on tree bark for mapping their
      deposition across metropolitan Sheffield by sampling 642 trees of three common
      species. Mean concentrations of metals were generally an order of magnitude
      greater than in samples from a remote uncontaminated site. We found trivially
      small differences among tree species with respect to metal concentrations on
      bark, and in subsequent statistical analyses did not discriminate between them.
      We mapped the concentrations of As, Cd and Ni by lognormal universal kriging
      using parameters estimated by residual maximum likelihood (REML). The
      concentrations of Ni and Cd were greatest close to a large steel works, their
      probable source, and declined markedly within 500 m of it and from there more
      gradually over several kilometres. Arsenic was much more evenly distributed,
      probably as a result of locally mined coal burned in domestic fires for many
      years. Tree bark seems to integrate airborne pollution over time, and our
      findings show that sampling and analysing it are cost-effective means of mapping
      and identifying sources.

PMID- 18078699
TI  - Available data on naphthalene exposures: strengths and limitations.
AB  - Exposures to naphthalene occur from a number of sources. Data on these exposures
      have been reported by a number of researchers; however, these data have not been
      organized into a consistent framework. In addition, while naphthalene has been
      identified as an animal inhalation carcinogen there has been no attempt to define
      the ranges of long-term average inhalation exposures for the general population
      or sub populations that are relevant to the assessment of the risk of the
      occurrence of chronic effects. This paper attempts to organize the available data
      on naphthalene levels in air and provide ranges for the long-term average
      concentrations experienced by different populations. The paper also discusses the
      limitations of available data and identifies areas for future research.

PMID- 18078700
TI  - Risk of gastrointestinal cancers from inhalation and ingestion of asbestos.
AB  - This paper summarizes the weight of epidemiological evidence to evaluate the
      hypothesis that asbestos exposure is causally associated with increased risk of
      gastrointestinal (GI) cancers as suggested by Selikoff in an early study of
      insulation workers. This review looks at populations that develop GI cancers,
      namely stomach, colorectal, colon and rectal. Guidelines for assessing causality
      are strength of association, biological gradient and consistency of the
      associations. Exposure-response (E-R) was evaluated using three methods to
      estimate exposure. Rate Ratios (RRs) for lung cancer and percent of mesothelioma
      are used as surrogate measures of asbestos exposure for all the cohorts of
      exposed workers. Quantitative or semi-quantitative estimates of cumulative
      exposure to asbestos were also used to assess E-R trends and were compared to E-R
      trends for lung cancer and mesothelioma in individual studies. Surrogate measures
      are important since there are few individual studies that have assessed E-R. None
      of the various methods to estimate asbestos exposure yielded consistent E-R
      trends and the strength of the associations were consistently weak or non
      existent for the four types of GI cancers. The epidemiological evidence detracts
      from the hypothesis that occupational asbestos exposure increases the risk of
      stomach, colorectal, colon, and rectal cancer. Findings are briefly summarized
      below.

PMID- 18078701
TI  - Effects of green tea extract on learning, memory, behavior and
      acetylcholinesterase activity in young and old male rats.
AB  - OBJECTIVE: To study the effects of green tea extract administration on age
      related cognition in young and old male Wistar rats. METHODS: Young and old rats
      were orally administered 0.5% green tea extract for a period of eight weeks and
      were evaluated by passive avoidance, elevated maze plus paradigm and changes in
      acetylcholinesterase activity. RESULTS: Treatment of young and old rats with the
      extract resulted in no significant difference in performance on the rota rod
      treadmill test/righting reflex time. Green tea extract significantly improved
      learning and memory in older rats, with increased retention latency to enter
      difference in passive avoidance test. In the elevated maze test, green tea
      treatment resulted in significantly more number of entries in the enclosed arm by
      the young and old rats. Decline in acetylcholinesterase activity was observed in
      the cerebrum of green tea treated old rats in comparison to the green tea treated
      young rats. CONCLUSION: Green tea extract administration is effective in
      enhancing learning and memory in aged rats, and hence, may serve useful in
      reversing age-related deficits.

PMID- 18078702
TI  - Toxicologic evaluation of modified gum acacia: mutagenicity, acute and subchronic
      toxicity.
AB  - Modified gum acacia, produced from acacia gum by a process analogous to the
      production of modified food starch, was tested for mutagenicity in the microbial
      reverse mutation assay. The assay employed a wide range of dose levels, both with
      and without metabolic activation. Test results gave no indication that modified
      gum acacia possessed any mutagenic potential. The acute oral toxicity of modified
      gum acacia was determined in two studies employing Sprague-Dawley rats, and the
      LD50 values were found to be >2000 mg/kg. The primary dermal irritation potential
      of modified gum acacia was evaluated in rabbits by the Draize method. Test
      results indicated that modified gum acacia was slightly irritating by the
      Environmental Protection Agency (EPA) classification but not a primary irritant
      by Consumer Product Safety Commission (CPSC) guidelines. The subchronic toxicity
      of modified gum acacia was examined in Sprague-Dawley rats fed diets containing
      0%, 1%, 2.5%, and 5% modified gum acacia for 13 weeks. No dose-related effects on
      survival, growth, hematology, blood chemistry, organ weights, or pathologic
      lesions were observed. Results of these studies indicate that modified gum acacia
      does not possess mutagenic potential and that animals are not adversely affected
      by acute or subchronic exposure to modified gum acacia.

PMID- 18078703
TI  - Cytotoxicity of fig fruit latex against human cancer cells.
AB  - Fig fruit latex (FFL) contains significant amounts of polyphenolic compounds and
      can serve as a source of antioxidants after human consumption. The purpose of
      this study is to confirm anticancer activity of FFL against human cancer cells
      and to further elucidate its mechanism of activity. Human glioblastoma,
      hepatocellular carcinoma, and normal liver cells were used for in vitro tests of
      FFL effects. Those tests included cytotoxicity, colony formation inhibition, Brdu
      incorporation, acridine orange/ethidium bromide (AO/EB) staining for apoptotic
      cells, cell cycle distribution through flow cytometry (FCM), and ADP
      ribosyltransferase (NAD+; poly(ADP-ribose) polymerase)-like 1 (ADPERL1) mRNA
      expression through RT-PCR in response to FFL treatment. After FFL treatment, the
      proliferation, colony formation, and Brdu labeling indices of cancer cells
      decreased (P<0.05), while the AO/EB stained apoptotic cells increased (P<0.05).
      By FCM analysis, an increase of G(0)/G(1) phase cell population and decrease of S
      and G(2)/M phase cells were observed (P<0.01), while both ADPRTL1 mRNA expression
      and apoptotic indices increased (P<0.01). The findings in these studies suggested
      that FFL exhibited potent cytotoxicity in some human cancer cells with little
      effect in normal cells at certain concentration. The mechanism for such effects
      might be associated with the inhibition of DNA synthesis, induction of apoptosis,
      and cell cycle arrest of cancer cells.

PMID- 18078704
TI  - Assessment of fluoride concentration and daily intake by human from tea and
      herbal infusions.
AB  - The fluoride content in infusions of commercially available black, green, oolong,
      pu-erh and white teas was determined by ion-selective electrode. Herbal infusions
      as well as instant tea and ready-to-drink tea beverages were also examined. It is
      found that brewing time (5, 10 and 30 min) does increase the fluoride content,
      which in infusions of black tea (5 min brewing) was higher than that in the other
      types of tea, with contents ranging between 0.32 and 4.54 mg/l for black tea to
      0.37-0.54 mg/l for white tea and with even lower values for herbal tea infusions
      of 0.02-0.09 mg/l. On the basis of the results obtained, the daily intake of
      fluoride provided from tea and herbal beverages was estimated for an adult person
      and for children in comparison with the Polish SAI (Safe and Adequate Daily
      Intake) of fluoride which is strictly attributable to ADI (Acceptable Daily
      Intake). The fluoride intake resulted from the regular consumption of black tea
      infusions was raised as compared to the other types of teas as well as herbal
      teas. For adult and children tea drinkers consuming five cups of black tea per
      day the intake of fluoride will be in the range of 8.0-303% and 12-303% of the
      SAI, respectively. People are often exposed to multiple sources of fluoride, such
      as in food, water, air and excessive use of toothpaste. The control of tea
      quality is important to protect human against too high uptake of this element
      from black tea, which is the most popular beverage. Excessive intake of fluoride
      with black tea, especially in the regions with its high level in the drinking
      water, increases the risk of dental fluorosis in children during the years of
      tooth development. The long-term exposure to large amounts of fluoride can lead
      to potentially skeletal fluorosis (WHO, 1984).

PMID- 18078705
TI  - Investigation of the effect of a panel of model hepatotoxins on the Nrf2-Keap1
      defence response pathway in CD-1 mice.
AB  - The Keap1-Nrf2-ARE signalling pathway has emerged as an important regulator of
      the mammalian defence system to enable detoxification and clearance of foreign
      chemicals. Recent studies by our group using paracetamol (APAP), diethylmaleate
      and buthionine sulphoximine have shown that for a given xenobiotic molecule, Nrf2
      induction in the murine liver is associated with protein reactivity and
      glutathione depletion. Here, we have investigated, in vivo, whether the ability
      of four murine hepatotoxins, paracetamol, bromobenzene (BB), carbon tetrachloride
      (CCl4) and furosemide (FS) to deplete hepatic glutathione (GSH) is related to
      induction of hepatic Nrf2 nuclear translocation and Nrf2-dependent gene
      expression. Additionally, we studied whether hepatic Nrf2 nuclear translocation
      is a general response during the early stages of acute hepatic chemical stress in
      vivo. Male CD-1 mice were administered APAP (3.5 mmol/kg), FS (1.21 mmol/kg), BB
      (4.8 mmol/kg) and CCl4 (1 mmol/kg) for 1, 5 and 24h. Each compound elicited
      significant serum ALT increases after 24h (ALT U/L: APAP, 3036+/-1462; BB, 5308+/
      2210; CCl4, 5089+/-1665; FS, 2301+/-1053), accompanied by centrilobular damage as
      assessed by histopathology. Treatment with APAP also elicited toxicity at a much
      earlier time point (5h) than the other hepatotoxins (ALT U/L: APAP, 1780+/-661;
      BB, 161+/-15; CCl4, 90+/-23; FS, 136+/-27). Significant GSH depletion was seen
      with APAP (9.6+/-1.7% of control levels) and BB (52.8+/-6.2% of control levels)
      1h after administration, but not with FS and CCl4. Western Blot analysis revealed
      an increase in nuclear Nrf2, 1h after administration of BB (209+/-10% control),
      CCl4 (146+/-3% control) and FS (254+/-41% control), however this was
      significantly lower than the levels observed in the APAP-treated mice (462+/-36%
      control). The levels of Nrf2-dependent gene induction were also analysed by
      quantitative real-time PCR and Western blotting. Treatment with APAP for 1h
      caused a significant increase in the levels of haem oxygenase-1 (HO-1; 2.85-fold)
      and glutamate cysteine ligase (GCLC; 1.62-fold) mRNA. BB and FS did not affect
      the mRNA levels of either gene after 1h of treatment; however CCl4 significantly
      increased HO-1 mRNA at this time point. After 24h treatment with the
      hepatotoxins, there was evidence for the initiation of a late defence response.
      BB significantly increased both HO-1 and GCLC protein at this time point, CCl4
      increased GCLC protein alone, although FS did not alter either of these proteins.
      In summary, we have demonstrated that the hepatotoxins BB, CCl4 and FS can induce
      a small but significant increase in Nrf2 accumulation in hepatic nuclei. However,
      this was associated with modest changes in hepatic GSH, a delayed development of
      toxicity and was insufficient to activate an early functional adaptive response
      to these hepatotoxins.

PMID- 18078706
TI  - Urocortin and the brain.
AB  - Urocortin is a member of the corticotropin-releasing hormone (CRH) family of
      peptides. In the brain, its potent suppression of food intake is mediated by CRH
      receptors (CRHR). Urocortin also participates in the regulation of anxiety,
      learning, memory, and body temperature, and it shows neuroprotection. This review
      will summarize the location of urocortin-producing neurons and their projections,
      the pharmacological evidence of its actions in the CNS, and information acquired
      from knockout mice. Urocortin interacts with leptin, neuropeptide Y, orexin, and
      corticotropin in the brain. Also produced by the GI tract, heart, and immune
      cells, urocortin has blood concentrations ranging from 13 to 152 pg/ml. Blood
      borne urocortin stimulates the cerebral endothelial cells composing the blood
      brain barrier and crosses the blood-brain barrier by a unique transport system.
      Overall, urocortin acts on a broad neuronal substrate as a neuromodulator
      important for basic survival.

PMID- 18078708
TI  - Square-wave jerks and smooth pursuit impairment as subtle early signs of brain
      involvement in Langerhans' cell histiocytosis.
AB  - Central nervous system (CNS) involvement in Langerhans' cell histiocytosis (LCH)
      has been described as a progressive neurological disorder marked by motor and
      cognitive decline. Detailed analysis of ocular motor abnormalities is lacking. We
      report on a 60-year-old male with histologically confirmed LCH who developed
      oscillopsia and gait ataxia over a 1-year period. Eye movements recorded with
      infrared oculography revealed a high rate of square-wave jerks (SWJ) with
      frequencies of 41 min(-1) on average and amplitudes between 1 degrees and 7
      degrees , as well as marked impairment of smooth tracking of sinusoidally moving
      targets. Furthermore, static posturography disclosed increased body sway, with an
      abnormally high sway path. The initial brain MRI was unremarkable. Due to the
      presumed cerebellar dysfunction we performed a second MRI 1 year later that
      disclosed deep cerebellar lesions compatible with LCH relapse within the CNS. The
      abnormal high SWJ rate and the impaired smooth pursuit performance correctly
      heralded later involvement of the cerebellum anticipating lesion appearance in
      the MRI.

PMID- 18078707
TI  - DISC1 is associated with prefrontal cortical gray matter and positive symptoms in
      schizophrenia.
AB  - BACKGROUND: DISC1 is considered a susceptibility gene for schizophrenia and
      schizoaffective disorder, but little is known regarding the potential mechanisms
      through which it may confer increased risk. Given that DISC1 plays a role in
      cerebral cortex development, polymorphisms in this gene may have relevance for
      neurobiological models of schizophrenia that have implicated cortical deficits in
      its pathophysiology. METHODS: We investigated whether the DISC1 leu607phe
      polymorphism was associated with prefrontal gray matter volumes using magnetic
      resonance imaging in a cohort of patients with schizophrenia (N=19) and healthy
      volunteers (N=25) and positive and negative symptoms in 200 patients with
      schizophrenia. RESULTS: Among patients and healthy volunteers, phe carriers
      (N=11) had significantly less gray matter in the superior frontal gyrus and
      anterior cingulate gyrus compared to leu/leu homozygotes (N=33). Further, among
      patients left superior frontal gyrus gray matter volume was significantly
      negatively correlated with severity of hallucinations. In addition, patients who
      were phe carriers (N=144) had significantly greater severity of positive symptoms
      (hallucinations) compared to patients who were leu/leu homozygotes (N=56).
      DISCUSSION: These findings implicate DISC1 in variation of prefrontal cortical
      volume and positive symptoms, thus providing a potential mechanism through which
      DISC1 may confer increased risk for schizophrenia or schizoaffective disorder.

PMID- 18078709
TI  - Inhibition of Src reduces gemcitabine-induced cytotoxicity in human pancreatic
      cancer cell lines.
AB  - In the present study, we examined the role of Src in gemcitabine-induced cell
      growth suppression in human pancreatic cancer cell lines. In two human pancreatic
      cancer cell lines, PK-9 and MIA PaCa-2, we found that a selective Src protein
      tyrosine kinase inhibitor, PP2, inhibited gemcitabine-induced cell growth
      suppression. When dominant negative src cDNA was constitutively expressed in PK-9
      cells (PK-9-Src-DN), the degree of gemcitabine-induced cell growth suppression
      was decreased compared with that of mock-transfected PK-9 cells. The mechanism of
      the inhibitory effect of gemcitabine-induced cytotoxicity was found to be the
      suppression of apoptosis, which was downregulated in PK-9-Src-DN cells. These
      results indicate that Src mediates signals that culminate in suppressing cell
      growth and survival in the presence of gemcitabine, at least in particular cell
      lines.

PMID- 18078710
TI  - Wastewater treatment in a hybrid activated sludge baffled reactor.
AB  - A novel hybrid activated sludge baffled reactor (HASBR), which contained both
      suspended and attached-growth biomass perfect mixing cells in series, was
      developed by installing standing and hanging baffles and introducing plastic
      brushes into a conventional activated sludge (CAS) reactor. It was used for the
      treatment of domestic wastewater. The effects on the operational performance of
      developing the suspended and attached-growth biomass and reactor configuration
      were investigated. The change of the flow regime from complete-mix to plug-flow,
      and the addition of plastic brushes as a support for biofilm, resulted in
      considerable improvements in the COD, nitrogen removal efficiency of domestic
      wastewater and sludge settling properties. In steady state, approximately 98+/-2%
      of the total COD and 98+/-2% of the ammonia of the influent were removed in the
      HASBR, when the influent wastewater concentration was 593+/-11 mg COD/L and 43+/
      5 mg N/L, respectively, at a HRT of 10 h. These results were 93+/-3 and 6+/-3%
      for the CAS reactor, respectively. Approximately 90+/-7% of the total COD was
      removed in the HASBR, when the influent wastewater concentration was 654+/-16 mg
      COD/L at a 3h HRT, and in the organic loading rate (OLR) of 5.36kgCOD m(-3) day(
      1). The result for the CAS reactor was 60+/-3%. Existing CAS plants can be
      upgraded by changing the reactor configuration and introducing biofilm support
      media into the aeration tank.

PMID- 18078711
TI  - Leaching of lead by ammonium salts and EDTA from Salvinia minima biomass produced
      during aquatic phytoremediation.
AB  - Plant biomass harvested after heavy-metal phytoremediation must be considered as
      a hazardous waste that should be contained or treated appropriately before
      disposal or reuse. As a potential method to detoxify the biomass and to convert
      this material to a suitable fertilizer or mulch, leaching of lead (Pb) from
      Salvinia minima biomass was studied by testing water, several aqueous ammonium
      salts, and EDTA solution as lead extractants. The research was carried out in two
      phases: (i) a leaching study to determine the lead-extraction efficiency of the
      different leachants, and (ii) a thermodynamic analysis to identify the likely
      reactions and stable Pb(II) species formed in the leaching systems of the most
      efficient leachants. Experimentally, lead concentrations measured in leached
      biomass and in leachates were significantly different among the various
      leachants. It was determined that the extraction strength of the leachants
      followed the order: EDTA>ammonium oxalate>water approximately ammonium
      nitrate>ammonium acetate, achieving Pb extraction efficiencies of 99%, 70%, 7.2%,
      6.9% and 1.3%, respectively, in single-stage extractions. The thermodynamic study
      indicated that the dominant species produced by the leaching process should be
      the soluble species PbEDTA2- for EDTA system, and the insoluble Pb(COO)2S
      precipitate for the oxalate system.

PMID- 18078712
TI  - Removal of As(V) and Cr(VI) from aqueous solutions using solid waste from leather
      industry.
AB  - This study evaluated the feasibility of using a solid waste from the leather
      industry as an adsorbent for removal of Cr(VI) and As(V) from aqueous media. The
      adsorbent material was characterized by chemical analyses, infrared spectroscopy,
      and scanning electronic microscopy (SEM) prior to reaction in order to assess its
      surface properties. Langmuir and Freundlich equations were used for analyzing the
      experimental data, which showed a better fit to the Langmuir model, thus
      suggesting a monolayer adsorption process in the surface of the adsorbent. The
      high amounts of Cr(VI)-133 mg g(-1) and As(V)-26 mg g(-1) adsorbed demonstrates
      the great potential for using this solid waste from the leather industry as a low
      cost alternative to the traditionally used adsorbent materials.

PMID- 18078713
TI  - Emergency planning and the Control of Major Accident Hazards (COMAH/Seveso II)
      Directive: an approach to determine the public safety zone for toxic cloud
      releases.
AB  - The EU Control of Major Accidents Hazards Directive (Seveso II) requires an
      external emergency plan for each top tier site. This paper sets out a method to
      build the protection of public health into emergency planning for Seveso sites in
      the EU. The method involves the review of Seveso site details prescribed under
      the directive. The site safety report sets out the potential accident scenarios.
      The safety report's worst-case scenario, and chemical involved, is used as the
      basis for the external emergency plan. A decision was needed on the appropriate
      threshold value to use as the level of concern to protect public health. The
      definitions of the regulatory standards (air quality standards and occupational
      standards) in use were studied, how they are derived and for what purpose. The 10
      min acute exposure guideline level (AEGL) for a chemical is recommended as the
      threshold value to inform decisions taken to protect public health from toxic
      cloud releases. The area delimited by AEGL 1 defines the population who may be
      concerned about being exposed. They need information based on comprehensive risk
      assessment. The area delimited by AEGL 2 defines the population for long-term
      surveillance when indicated and may include first responders. The area delimited
      by AEGL 3 defines the population who may present acutely to the medical services.
      It ensures that the emergency responders site themselves safely. A standard
      methodology facilitates discussions with plant operators and concerned public.
      Examples show how the methodology can be adapted to suit explosive risk and
      response to fire.

PMID- 18078714
TI  - Biosorption of Cr (VI) from aqueous solutions by biomass of Agaricus bisporus.
AB  - In this study, biosorption of Cr (VI) ion was investigated by using biomass of
      Agaricus bisporus (a species of mushroom) in a temperature and shaking speed
      controlled shaker. The effect of shaking speed, biomass concentration, initial
      metal ion concentration and initial pH on biosorption yield was determined and
      the fitness of biosorption data for Freundlich and Langmuir adsorption models was
      investigated. Optimum biosorption conditions were found to be pH 1, C0=50 mg/l,
      m=10 g/l, shaking speed=150 rpm, T=20 degrees C Cr (VI), respectively. It was
      found that biosorption of Cr (VI) ions onto biomass of A. bisporus was better
      suitable to Freundlich adsorption model than Langmuir adsorption model. The
      correlation coefficients for the second-order kinetic model obtained were found
      to be 0.999 for all concentrations. These indicate that the biosorption system
      studied belongs to the second-order kinetic model.

PMID- 18078715
TI  - Dendritic branching features of posterodorsal medial amygdala neurons of adult
      male and female rats: further data based on the Golgi method.
AB  - The posterodorsal portion of the medial amygdalar nucleus (MePD) contains
      receptors for gonadal hormones and modulates the function of a social behavior
      network in rodents. The aims of this study were: to provide further data about
      the morphology of Golgi-impregnated dendrites of neurons from the MePD of adult
      rats; and, to compare the results obtained for dendritic branching and
      predominant dendritic spatial distribution in the MePD of males and diestrus
      females. MePD neurons were classified as bitufted or stellate, their spiny
      dendrites showed variable lengths, divided sparingly and decreased the number of
      branches with the distance from the soma. Dendritic arborization levels, number
      of branches in each level, distribution of the dendrites around the cell body and
      away from it, and the preferred spatial distribution of dendritic branches were
      studied according to different techniques and compared between sexes.
      Statistically significant differences were found in the predominant dendritic
      spatial distribution in the MePD, males with branches more oriented medially and
      dorsolaterally and females with more dorsally and ventromedially ones (p< or
      =0.05 in all cases). This result adds another clue to understand how information
      is processed and integrated in the MePD and within functionally dynamic sex
      steroids-responsive circuits relevant for reproduction in both sexes.

PMID- 18078716
TI  - 14-3-3zeta is indispensable for aggregate formation of polyglutamine-expanded
      huntingtin protein.
AB  - Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative
      disorder caused by polyglutamine (polyQ) expansions in the huntingtin (Htt)
      protein. A hallmark of HD is the presence of aggregates-predominantly composed of
      NH(2)-terminal fragments of polyQ-expanded Htt-in the nucleus and cytoplasm of
      affected neurons. We previously proposed that 14-3-3zeta might act as a sweeper
      of misfolded proteins by facilitating the formation of aggregates possibly for
      neuroprotection; these aggregates are referred to as inclusion bodies. However,
      evidence available in this regard is indirect and circumstantial. In this study,
      analysis of the aggregation-prone protein Htt encoded by HD gene exon 1
      containing polyglutamine expansions (Htt86Q) revealed that 17 residues in the
      NH(2)-terminal of this protein are indispensable for its aggregate formation.
      Immunoprecipitation assays revealed that 14-3-3beta, gamma, eta, and zeta
      interact with Htt86Q transfected in N2a cells. Interestingly, the small
      interfering ribonucleic acid (siRNA) suppression of 14-3-3zeta exclusively
      abolished Htt86Q aggregate formation, whereas 14-3-3beta or eta siRNA suppression
      did not. This indicates that 14-3-3zeta participates in aggregate formation under
      nonnative conditions. Our data support a novel role for 14-3-3zeta in the
      aggregate formation of nonnative, aggregation-prone proteins.

PMID- 18078717
TI  - Comparative histopathology and antibody responses of non-Tritrichomonas foetus
      trichomonad and Tritrichomonas foetus genital infections in virgin heifers.
AB  - The potential pathogenicity of non-Tritrichomonas foetus trichomonads (NTfTs)
      recently isolated from the prepuce of virgin bulls is not known. The purpose of
      this study was to determine the ability of these NTfTs to cause disease in the
      female reproductive tract relative to T. foetus. Forty-four virgin heifers were
      experimentally infected intravaginally with either one of two NTfTs
      (Pentatrichomonas hominis or Tetratrichomonas spp.), T. foetus, or sterile media
      and cultured weekly from 0 time until slaughter at 8 weeks. Serum and vaginal
      antibody responses during infection were assessed, and the reproductive tracts
      were histologically examined, scored, and compared based on numbers of
      neutrophils, eosinophils, lymphocytes, and plasma cells as well as the
      qualitative appearance of the reproductive tract. The NTfTs did not persist in
      the reproductive tract, while T. foetus persisted for at least 6-8 weeks.
      Further, no vaginal IgA response to infection was found in NTfT-infected and
      control heifers, but a vaginal IgA response was present in the T. foetus-infected
      group. Heifers infected with NTfT or controls showed little mucosal inflammatory
      response compared to T. foetus-infected heifers. Among the trichomonads studied,
      persistent infection by T. foetus alone seems responsible for uterine
      inflammatory lesions usually associated with pregnancy loss. The NTfTs studied in
      this work only transiently infected the vagina and were associated with strictly
      mild inflammatory changes, which probably do not cause significant disease, i.e.,
      pregnancy loss.

PMID- 18078718
TI  - A new treatment for chronic itch?

PMID- 18078719
TI  - Comparison of intensity-modulated radiotherapy planning based on manual and
      automatically generated contours using deformable image registration in four
      dimensional computed tomography of lung cancer patients.
AB  - PURPOSE: To evaluate the implications of differences between contours drawn
      manually and contours generated automatically by deformable image registration
      for four-dimensional (4D) treatment planning. METHODS AND MATERIALS: In 12 lung
      cancer patients intensity-modulated radiotherapy (IMRT) planning was performed
      for both manual contours and automatically generated ("auto") contours in mid and
      peak expiration of 4D computed tomography scans, with the manual contours in peak
      inspiration serving as the reference for the displacement vector fields. Manual
      and auto plans were analyzed with respect to their coverage of the manual
      contours, which were assumed to represent the anatomically correct volumes.
      RESULTS: Auto contours were on average larger than manual contours by up to 9%.
      Objective scores, D(2%) and D(98%) of the planning target volume, homogeneity and
      conformity indices, and coverage of normal tissue structures (lungs, heart,
      esophagus, spinal cord) at defined dose levels were not significantly different
      between plans (p = 0.22-0.94). Differences were statistically insignificant for
      the generalized equivalent uniform dose of the planning target volume (p = 0.19
      0.94) and normal tissue complication probabilities for lung and esophagus (p =
      0.13-0.47). Dosimetric differences >2% or >1 Gy were more frequent in patients
      with auto/manual volume differences > or =10% (p = 0.04). CONCLUSIONS: The
      applied deformable image registration algorithm produces clinically plausible
      auto contours in the majority of structures. At this stage clinical supervision
      of the auto contouring process is required, and manual interventions may become
      necessary. Before routine use, further investigations are required, particularly
      to reduce imaging artifacts.

PMID- 18078720
TI  - Use of external beam radiotherapy is associated with reduced incidence of second
      primary head and neck cancer: a SEER database analysis.
AB  - PURPOSE: Patients with head and neck cancer have a significant risk of developing
      a second primary cancer of the head and neck. We hypothesized that treatment with
      external beam radiotherapy (RT) might reduce this risk, because RT can eradicate
      occult foci of second head and neck cancer (HNCA). METHODS AND MATERIALS: The
      data of patients with Surveillance, Epidemiology, and End Results Historic Stage
      A localized squamous cell carcinoma of the oral cavity, larynx, and pharynx were
      queried using the Surveillance, Epidemiology, and End Results database. For
      patients treated with or without RT, the incidence of second HNCA was determined
      and compared using the log-rank method. Cox proportional hazards analysis was
      performed for each site, evaluating the influence of covariates on the risk of
      second HNCA. RESULTS: Between 1973 and 1997, 27,985 patients were entered with
      localized HNCA. Of these patients, 44% had received RT and 56% had not. The 15
      year incidence of second HNCA was 7.7% with RT vs. 10.5% without RT (hazard ratio
      0.71, p <0.0001). The effect of RT was more profound in patients diagnosed
      between 1988 and 1997 (hazard ratio 0.53, p <0.0001) and those with pharynx
      primaries (hazard ratio 0.47, p <0.0001). On multivariate analysis, RT was
      associated with a reduced risk of second HNCA for pharynx (p <0.0001) and larynx
      (p = 0.04) tumors. For oral cavity primaries, RT was associated with an increased
      risk of second HNCA in patients treated before 1988 (p <0.001), but had no
      influence on patients treated between 1988 and 1997 (p = 0.91). CONCLUSION: For
      localized HNCA, RT is associated with a reduced incidence of second HNCA. These
      observations are consistent with the eradication of microscopic foci of second
      HNCA with external beam RT.

PMID- 18078721
TI  - Song recognition memory in juvenile zebra finches: effects of varying the number
      of presentations of heterospecific and conspecific songs.
AB  - Seven male and three female zebra finches were exposed to 14 zebra finch (CON)
      and 14 starling (HET) songs during their sensitive period for song learning and
      then tested for their recognition memory of both the CON and HET songs in two
      separate memory tests. Amount of song exposure was varied by presenting
      individual songs either 3, 9, 27, or 81 times per day for nine consecutive days.
      After song exposure the birds were trained to discriminate two of the exposed,
      familiar songs (FAM) from two novel songs (NOV) in a go/no-go operant
      discrimination procedure, with FAM songs as "go" stimuli. Following
      discrimination training, untrained FAM and NOV songs were presented as probe
      songs without reinforcement. Birds responded more to FAM than NOV songs at all
      levels of song exposure, indicating that the songs were recognized. There were no
      differences in recognition memory for CON and HET song at any level of song
      exposure. The results suggest that selective song learning does not result from
      selective memorization of conspecific song.

PMID- 18078722
TI  - Drug use expectancies among nonabstinent community cocaine users.
AB  - Previous research has shown that one's expectations about the effects of using a
      particular substance (i.e., substance use expectancies) are associated with the
      quantity and frequency of actual use. An extensive literature supports the
      importance of expectancies in predicting alcohol use, but less is known about the
      association between expectancies and use of other substances. The purpose of the
      present investigation was to examine the association between cocaine expectancies
      and frequency of use in a heterogeneous community sample of drug users.
      Participants were 157 self-identified primary cocaine users recruited from the
      community as part of a hepatitis prevention study. Participants completed a
      structured interview that assessed demographic variables, current and past drug
      use, and drug expectancies. Results from multivariate logistic regression
      analyses indicated that frequency of cocaine use was positively associated with
      higher expectation that drug use would increase social and physical pleasure
      (OR=1.67, p<0.05) and inversely associated with higher expectation that drug use
      would increase cognitive and physical impairment (OR=0.59, p<0.01). These
      findings suggest that drug use expectancies are an important correlate of cocaine
      use behavior in nontreatment-seeking community users.

PMID- 18078723
TI  - Residual effects of intranasal methamphetamine on sleep, mood, and performance.
AB  - Although intranasal methamphetamine abuse has increased, there are no published
      data investigating the residual effects of the drug under controlled conditions.
      Thus, the current study examined the residual effects of single-dose intranasal
      methamphetamine administration on a broad range of behavioral and physiological
      measures. Non-treatment seeking methamphetamine abusers (n=11) completed this two
      week, in patient, within-participant, double-blind study. The study consisted of
      four two-day blocks of sessions; each block was separated by at least 48 h. At
      approximately 10:00 h, on the first day of each block, participants received one
      of four intranasal methamphetamine doses (0, 12, 25, 50mg/70 kg). Lights were
      turned out at 23:00 h that evening and sleep measures were assessed. On the
      morning of the second day of each block, methamphetamine plasma levels,
      cardiovascular measures, mood, subjective reports of the previous evening's
      sleep, and psychomotor performance were assessed to determine residual drug
      effects. The larger methamphetamine doses (25 and 50 mg) markedly disrupted
      subjective measures of that night's sleep and some indices of next-day mood, but
      only the largest dose (50 mg) dose decreased objective measures of that night's
      sleep and increased next-day physiological measures. Methamphetamine did not
      produce any negative residual effects on early next-day performance. Future
      studies should assess methamphetamine-related residual effects following repeated
      doses administered over consecutive days.

PMID- 18078724
TI  - Association of microsatellite (GT)n polymorphism at 3'UTR of NRAMP1 with the
      macrophage function following challenge with Brucella LPS in buffalo (Bubalus
      bubalis).
AB  - Brucella abortus is a facultative intracellular pathogen that survives and
      replicates in host macrophages. Hence, macrophage function plays an important
      role in influencing natural resistance/susceptibility to intracellular pathogen.
      The natural resistance associated macrophage protein 1 (NRAMP1; erstwhile
      referred as Ity/Lsh/Bcg), a transmembrane protein, regulates activity of
      macrophages against intracellular pathogens. In bovine, natural resistance to
      brucellosis is significantly associated with (GT)13 allelic variant of
      microsatellite locus at 3' untranslated region (3'UTR) of the NRAMP1 gene. In the
      present study we screened 65 Murrah breed of buffalo (Bubalus bubalis) to
      identify polymorphism at 3'UTR of NRAMP1 gene and evaluate the association of
      these polymorphisms with the macrophage function. Four allelic variants (viz.,
      GT13, GT14, GT15 and GT16) were identified. Majority of the buffaloes were of
      either homozygous (GT)14/(GT)14 or heterozygous (GT)14/(GT)15 with (GT)14 allele
      occurring most frequently (62%). For association study, non-vaccinated and
      serologically negative animals were divided into three genotypic groups: group 1
      (n=2) comprising animals of homozygous (GT)13 genotype, whereas, group 2 (n=4)
      and group 3 (n=6) consisted animals of heterozygous [(GT)13/(GT)n, where n not
      equal 13] and non-(GT)13 [(GT)n/(GT)n, where n not equal 13] genotype,
      respectively. Macrophages, after maturation, were challenged with Brucella LPS to
      assay the macrophage function in terms of H2O2 and NO production. The (GT)13
      allele, either in homozygoous {(GT)13/(GT)13} or heterozygous {(GT)13/(GT)n,
      where n=14, 15 or 16}, was significantly (p<0.01) associated with increased
      production of H2O2 and NO. In this manuscript, for the first time, we have
      identified (GT)13 allelic variant and demonstrated its significant association
      with the improved macrophage function in buffalo.

PMID- 18078725
TI  - Effect of cationic lipid composition on properties of oligonucleotide/emulsion
      complexes: Physico-chemical and release studies.
AB  - This paper describes the influence of cationic lipid composition on physico
      chemical properties of complexes formed between oligonucleotides (ON) and
      cationic emulsions. Formulations containing medium chain triglycerides, egg
      lecithin, increasing amounts of either oleylamine (OA) or 1,2-dioleoyl-3
      trimethylammonium-propane (DOTAP), and water were prepared by a spontaneous
      emulsification procedure. ON adsorption on emulsions was evidenced by the
      inversion of the zeta-potential, the increase in droplet size, and the morphology
      of the oil droplet examined through transmission electron microscopy. Adsorption
      isotherms showed a higher amount of ON adsorbed on emulsions containing DOTAP
      when compared to emulsions containing OA. In a final step, the role of the main
      parameters, which may in fact influence the ON release rate from emulsions, was
      investigated. ON were progressively released from emulsions with an increase in
      dilution ratio and remained quite similar for both OA and DOTAP emulsions over
      time. Conversely, the effect of the cationic lipid composition was observed upon
      increasing the charge ratio of complexes. ON release at a same charge ratio was
      lower from emulsions containing DOTAP (bearing dioleyl chains) than from those
      containing OA (bearing monoleyl chain).

PMID- 18078726
TI  - Responses of cochlear nucleus neurons to harmonic and mistuned complex tones.
AB  - Preliminary measurements of the representation in the cochlear nucleus (CN) of
      harmonic tones, harmonic tones with mistuned components, and double harmonic
      tones are reported. These data indicate that, unlike auditory nerve fibers and IC
      neurons, neurons in the CN may exhibit one of several qualitatively different
      response patterns when stimulated with mistuned tones. Primary-like neurons
      synchronized their discharges to 2-3 individual stimulus components, much like
      auditory nerve fibers do. Chopper neurons tended to respond with the periodicity
      of envelopes produced by interactions between adjacent stimulus components but
      exhibited little or no response synchronized to individual stimulus components. A
      small proportion of CN neurons exhibited complex slowly-modulated discharge
      patterns similar to those that are commonly observed in the inferior colliculus
      (IC). The patterns obtained from CN neurons with different pure tone discharge
      patterns were generally consistent with expectations based on previous studies
      with other stimuli. The measurements provided additional insight into the
      hierarchical processing stages that result in the highly patterned responses of
      IC neurons to harmonic and mistuned tones.

PMID- 18078727
TI  - Genotoxicity testing of Cecropia obtusifolia extracts in two in vivo assays: the
      wing somatic mutation and recombination test of Drosophila and the human
      cytokinesis-block micronucleus test.
AB  - Cecropia obtusifolia Bertol. (Cecropiaceae) is a tree that grows in secondary
      vegetation in the tropical rain forest along both coasts of Mexico. Its leaves
      are used in folk medicine for the treatment of diabetes mellitus type 2. The aim
      of the present studies was the evaluation of possible genotoxic effects of the
      aqueous extract from the leaves of Cecropia obtusifolia by means of two different
      experimental assay models: the wing somatic mutation and recombination test in
      flies and the micronucleus test from lymphocytes obtained from patients treated
      with the extract. No toxicity was found to be induced by the leaves of Cecropia
      obtusifolia. The Drosophila wing somatic mutation and recombination test (SMART)
      was applied in the standard version with basal biotransformation activity as well
      as in a variant version with increased cytochrome P450-dependent bioactivation
      capacity. The ranges of exposure concentrations for these genotoxicity
      experiments were between 0.82 and 13.32 mg/ml. The extract did not produce any
      genotoxic effect; however it showed a non significant antigenotoxic effect. The
      human micronucleus assay in vivo was performed with cultured lymphocytes obtained
      from six diagnosed type 2 diabetic patients treated daily with 13.5 g of the
      aqueous extract between 32 and 85 days. No statistically significant increases in
      cytotoxicity and/or genotoxicity between control and diabetic blood samples were
      observed.

PMID- 18078728
TI  - Acute encephalitis with refractory, repetitive partial seizures.
AB  - BACKGROUND: Acute encephalitis with refractory, repetitive partial seizures
      (AERRPS) is a new epileptic syndrome described by Sakuma in Japan in 2001. The
      clinical manifestations, neuroimaging findings and outcome of AERRPS in Taiwan
      have not been reported. METHODS: From 2000 to 2006, we collected cases that
      fulfilled the diagnostic criteria of AERRPS and analyzed the clinical course,
      virology, medication, electroencephalographic findings, neuroimaging characters
      and prognosis retrospectively. RESULTS: Fourteen children aged from 1 year and 2
      months to 15 years and 6 months were enrolled. They presented with prodromic
      symptoms including fever (n=13, 92.9%), upper respiratory tract infection
      symptoms (n=12, 85.7%) and gastrointestinal tract discomfort (n=6, 42.9%).
      Seizures occurred 3-14 days after antecedent symptoms with patterns of
      generalized tonic-clonic seizures, focal seizures or myoclonic seizures. The
      seizures were refractory to combinations of antiepileptic drugs (AEDs). Prolonged
      fever (n=14, 100.0%), hypersensitivity to AEDs (n=11, 78.6%) and liver function
      impairment (n=8, 57.1%) were noted during the period of hospitalization. The
      follow-up EEG findings were similar to those of initial findings including
      epileptiform discharges and/or generalized background slow waves. Initial brain
      MRI scans were normal but later showed focal or multifocal abnormal signal
      intensity followed by generalized brain atrophy in more than 50% of cases. The
      general prognosis was poor with variable psychomotor retardation and persistence
      of refractory epileptic seizures. CONCLUSIONS: The similarities of the clinical
      features support AERRPS as a new epileptic syndrome. More study is needed to
      specify the etiology of the syndrome as the first step for more effective
      treatment.

PMID- 18078729
TI  - Brain aging: The zinc connection.
AB  - At variance with other organs, where the functional and structural units are
      repeated, the brain is a composite assembly of groups of cells with different
      metabolic features and functional units. Deterioration of brain function occurs
      when the number of neurons or their connections decrease below a critical reserve
      level and coping with environmental stimulation is seriously hampered.
      Physiopathological alterations of the synaptic junctional areas are reported to
      play a central role in the process of brain aging. Current research is
      documenting an age-related numeric loss of synapses which is paired by a
      significant enlargement of the persisting contact zones: the final outcome of
      these balanced changes is a significant reduction of the overall synaptic
      junctional area per unit volume of neuropil. The progressive decline of the
      mitochondrial metabolic competence, i.e. the capacity of select pools of
      organelles to provide adequate amounts of adenosine triphosphate is supposed to
      represent a key determinant in synaptic aging. Cytochemical estimations of the
      activity of cytochrome oxidase confirm that mitochondrial dysfunctions play an
      early role in synaptic deterioration. Zinc ions act as physiological
      neuromodulators at glutamatergic synapses, however, in order to avoid neurotoxic
      damage, the intracellular free Zn(++) concentration ([Zn(++)](i)) must be tightly
      controlled by: (i) extrusion (Zn(++) transporters); (ii) buffering
      (metallothioneins) and (iii) sequestration (mitochondria) systems. In
      physiological aging, if any of these systems is impaired and/or not adequately
      coordinated with the other two, the resulting significant rise of ([Zn(++)](i))
      may inhibit the cellular energy providing systems and affect mitochondria as
      primary target.

PMID- 18078730
TI  - Repletion of antioxidant status by EGCG and retardation of oxidative damage
      induced macromolecular anomalies in aged rats.
AB  - Ageing is defined as the loss of ability to maintain cellular homeostasis of an
      organism associated with the free radical-elicited oxidative damage to cellular
      macromolecules. The aim of this study was to evaluate the efficacy of
      epigallocatechin-3-gallate (EGCG), the key component of green tea catechins on
      attenuating the age associated oxidative perturbances by assessing the redox
      status in mitotic (liver) and post-mitotic (skeletal muscle) tissues of young and
      aged rats. From the results, we observed an increase in the marker for oxidative
      damage such as lipid peroxidation and protein carbonyl content in aged rats, when
      compared to young rats. This was accompanied with decreased levels of both
      enzymic and non-enzymic antioxidants and redox index. On supplementation with
      EGCG (100 mg/kg body weight by oral gavage for 30 days), the levels of lipid
      peroxidation and protein carbonyl content were significantly decreased in aged
      rats, possibly by enhancing the GSH redox status, and both enzymic and non
      enzymic antioxidants status. In conclusion, this study supports the beneficial
      effect of EGCG in alleviating oxidative disturbances in ageing and retard the age
      associated derangements in both mitotic and post-mitotic tissues.

PMID- 18078731
TI  - Effects of zinc supplementation on antioxidant enzyme activities in healthy old
      subjects.
AB  - A large body of experimental research indicates that oxidative stress contributes
      to the processes related to aging and age-related diseases. Trace elements,
      particularly zinc (Zn), are essential components of the endogenous enzymatic
      antioxidant defenses. The aim of this study was to determine the activity of
      three main antioxidant enzymes in plasma [i.e. superoxide dismutase (pSOD),
      catalase (CAT), glutathione peroxidase (GPx)] and of SOD in erythrocyte (eSOD) in
      a group of 1108 healthy elderly subjects from different European countries. The
      same enzymatic activities were evaluated in a subgroup of 108 subjects before and
      after Zn supplementation. We observed that eSOD activity increased with age,
      whereas plasma Zn decreased. Moreover, we found that women showed higher eSOD
      activity and lower plasma Zn compared to men. There were no age and gender
      related differences in the activities of pSOD, CAT and GPx. After Zn
      supplementation, the activities of Zn-dependent enzymes (pSOD and eSOD), as well
      as plasma Zn concentration, were significantly higher than before
      supplementation. These results were not influenced by age, gender, plasma Zn
      variations (Delta Zn) and geographic area. These data suggest the potential
      beneficial effects of Zn supplementation on Zn-dependent antioxidant enzymes in
      healthy elderly subjects.

PMID- 18078732
TI  - Reproducibility of a semi-automatic method for 6-point vertebral morphometry in a
      multi-centre trial.
AB  - PURPOSE: To evaluate the reproducibility of a semi-automated system for vertebral
      morphometry (MorphoXpress) in a large multi-centre trial. MATERIALS AND METHODS:
      The study involved 132 clinicians (no radiologist) with different levels of
      experience across 20 osteo-centres in Italy. All have received training in using
      MorphoXpress. An expert radiologist was also involved providing data used as
      standard of reference. The test image originate from normal clinical activity and
      represent a variety of normal, under and over exposed films, indicating both
      normal anatomy and vertebral deformities. The image was represented twice to the
      clinicians in a random order. Using the software, the clinicians initially marked
      the midpoints of the upper and lower vertebrae to include as many of the
      vertebrae (T5-L4) as practical within each given image. MorphoXpress performs the
      localisation of all morphometric points based on statistical model-based vision
      system. Intra-operator as well inter-operator measurement of agreement was
      calculated using the coefficient of variation and the mean and standard deviation
      of the difference of two measurements to check their agreement. RESULTS: The
      overall intra-operator mean differences in vertebral heights is 1.61+/-4.27% (1
      S.D.). The overall intra-operator coefficient of variation is 3.95%. The overall
      inter-operator mean differences in vertebral heights is 2.93+/-5.38% (1 S.D.).
      The overall inter-operator coefficient of variation is 6.89%. CONCLUSIONS: The
      technology tested here can facilitate reproducible quantitative morphometry
      suitable for large studies of vertebral deformities.

PMID- 18078734
TI  - Protective effect of (-)-epigallocatechin-gallate (EGCG) on lipid peroxide
      metabolism in isoproterenol induced myocardial infarction in male Wistar rats: a
      histopathological study.
AB  - This study aims to evaluate the preventive effect of (-)-epigallocatechin-gallate
      (EGCG) on lipid peroxides, enzymatic and non-enzymatic antioxidants and
      histopathological findings in isoproterenol (ISO)-induced rats. Myocardial
      infarction (MI) is induced in rats by subcutaneous injection of ISO (100 mg/kg
      body weight) at an interval of 24h for 2 days. ISO-treated rats show a
      significant increase in the levels of thiobarbituric acid reactive substances,
      lipid hydroperoxides in plasma and heart and plasma uric acid and a significant
      decrease in the activities of superoxide dismutase, catalase, glutathione
      peroxidase, glutathione reductase and glutathione-S-transferase in heart and the
      levels of reduced glutathione, vitamin C and vitamin E in plasma and the heart
      and ceruloplasmin in plasma. Oral pretreatment with EGCG (10, 20 and 30 mg/kg
      body weight) daily for a period of 21 days show significant decrease in the
      levels of lipid peroxidation products and uric acid and improved the antioxidant
      status by increasing the activities of antioxidant enzymes and non-enzymic
      antioxidants. Histopathological findings of the myocardial tissue show the
      protective effect of EGCG in ISO-induced rats. The effect at a dose of 30 mg/kg
      of EGCG was more pronounced than that of the other two doses (10 and 20 mg/kg
      body weight). Thus, the present study reveals that EGCG exerts cardioprotective
      effect against ISO-induced MI due to its free radical scavenging and antioxidant
      effects, which maintains the tissue defense system against myocardial damage.

PMID- 18078733
TI  - Nurse training of a patient-centered information procedure for CABG patients.
AB  - OBJECTIVE: At the study hospital, all elective coronary artery bypass graft
      (CABG) surgery patients were given similar, standardized information by the
      nurses. The nurses reported problems in establishing contact and interacting with
      patients when using this approach. To help remedy communication problems between
      nurses and CABG patients, a programme training nurses in a patient-centred
      information procedure was developed and implemented. This article describes how
      challenging interactions were recorded and analysed for training nurses in the
      patient-centred approach. METHOD: In group training for patient-centeredness,
      nurses presented audio-recordings of nurse-patient interactions they found
      problematic. These were used as a basis for discussions and training in the
      patient-centered approach. A set of cases was developed using a qualitative
      phenomenological approach, illustrating how the patient-centered approach could
      be applied to the difficult situations. RESULTS: The nurses found the patient
      centered approach particularly useful in situations when patients frequently
      asked questions, seemed to have difficulties expressing their worries, frequently
      complained, or when spouses expressed worries. CONCLUSION: Nurses found the
      patient-centered approach and the training procedure used in this study useful in
      their clinical work with CABG patients. PRACTICE IMPLICATIONS: This training
      which requires minimal resources and can be easily implemented, may guide the
      nurses in their interaction with patients. Providing a patient-centered approach
      to the CABG patients may enhance the nurse-patient contact and improve patients'
      hospital experience and subjective health.

PMID- 18078735
TI  - Antitubercular activities of novel benzothiazolo naphthyridone carboxylic acid
      derivatives endowed with high activity toward multi-drug resistant tuberculosis.
AB  - Sixteen novel 3-nitro-2-(sub)-5,12-dihydro-5-oxobenzothiazolo[3,2-a]-1,8
      naphthyridine-6-carboxylic acids were synthesized from 2,6-dimethoxynicotinic
      acid and 2-aminothiophenol and evaluated for their antitubercular activities in
      vitro and in vivo against Mycobacterium tuberculosis H(37) Rv (MTB) and multi
      drug resistant M. tuberculosis (MDR-TB). Among the synthesized compounds, 2-(1,4
      dioxa-8-azaspiro[4.5]dec-8-yl)-3-nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]-1,8
      naphthyridine-6-carboxylic acid (10n) was found to be the most active compound in
      vitro with MIC of 0.19 and 0.04 microM against MTB and MTR-TB, respectively.
      Compound 10n showed promising activity against MDR-TB and was 208 and 1137 times
      more potent than gatifloxacin and isoniazid, respectively. In the in vivo animal
      model 10n decreased the mycobacterial load in lung and spleen tissues with 2.81
      and 4.94-log(10) protections, respectively, at a dose of 50 mg/kg body weight.

PMID- 18078736
TI  - Psychosocial factors are associated with the antibody response to both thymus
      dependent and thymus-independent vaccines.
AB  - The present study examined the association between psychological stress, social
      support and antibody response to both thymus-dependent and thymus-independent
      vaccinations. Stressful life events in the previous year and customary social
      support were measured by standard questionnaires at baseline in 75 (41 females)
      healthy students. Antibody status was assessed at baseline, 4 and 18 weeks
      following vaccination with formaldehyde inactivated hepatitis A virus and
      pneumococcal polysaccharides, which induce thymus-dependent and -independent
      antibody responses respectively. Controlling for baseline antibody status, life
      event stress was negatively associated with antibody response to the hepatitis A
      vaccine at the 18-week follow-up; participants reporting a greater number of
      stressful life events had a poorer antibody response. There was no relationship
      between psychological stress and antibody response to pneumococcal vaccination.
      Social support was not associated with the antibody response to hepatitis A
      vaccination. However, there was a significant association between support and the
      antibody response to the thymus-independent pneumococcal vaccine at 4-week follow
      up; participants with larger social networks mounted a better response. These
      relationships could not be accounted for by age and sex, or by variations in
      health behaviours. Psychosocial factors would appear to influence the response to
      both thymus-dependent and thymus-independent vaccines, but not in the same
      manner.

PMID- 18078737
TI  - The influence of anger expression on wound healing.
AB  - Certain patterns of anger expression have been associated with maladaptive
      alterations in cortisol secretion, immune functioning, and surgical recovery. We
      hypothesized that outward and inward anger expression and lack of anger control
      would be associated with delayed wound healing. A sample of 98 community-dwelling
      participants received standardized blister wounds on their non-dominant forearm.
      After blistering, the wounds were monitored daily for 8 days to assess speed of
      repair. Logistic regression was used to distinguish fast and slow healers based
      on their anger expression pattern. Individuals exhibiting lower levels of anger
      control were more likely to be categorized as slow healers. The anger control
      variable predicted wound repair over and above differences in hostility, negative
      affectivity, social support, and health behaviors. Furthermore, participants with
      lower levels of anger control exhibited higher cortisol reactivity during the
      blistering procedure. This enhanced cortisol secretion was in turn related to
      longer time to heal. These findings suggest that the ability to regulate the
      expression of one's anger has a clinically relevant impact on wound healing.

PMID- 18078738
TI  - Two-generation reproductive toxicity study of the rubber accelerator N,N
      dicyclohexyl-2-benzothiazolesulfenamide in rats.
AB  - Male and female Crl:CD(SD) rats were fed a diet containing rubber accelerator N,N
      dicyclohexyl-2-benzothiazolesulfenamide (DCBS) at 0, 80, 600 or 4500ppm
      throughout the study beginning at the onset of a 10-week pre-mating period and
      continuing through the mating, gestation, and lactation periods for two
      generations. At 4500ppm, decreases in the body weight, body weight gain, and food
      consumption were found in F0 males and females. No changes in the estrous
      cyclicity, copulation index, fertility index, gestation index, delivery index,
      number of implantations, precoital interval, or gestation length were observed in
      any generation at any dose of DCBS. Delayed preputial separation at 4500ppm as
      well as delayed vaginal opening and higher body weight at the age of vaginal
      opening at 600 and 4500ppm were found in the F1 generation. A transient change in
      performance in a water-filled multiple T-maze was found at 600 and 4500ppm in F1
      females. There were no compound-related changes in number of pups delivered, sex
      ratio of pups, viability of pups, anogenital distance, surface righting reflex,
      negative geotaxis reflex, mid-air righting reflex, pinna unfolding, incisor
      eruption, or eye opening in the F1 and F2 generations. The body weight of F1 and
      F2 male and female pups was lowered at 4500ppm. Reduced uterine weight of the
      weanlings was noted in the F1 generation at 4500ppm and in the F2 generation at
      600 and 4500ppm. The data indicate that the NOAEL of DCBS for two-generation
      reproductive toxicity is 80ppm (5.2mg/kgbw per day) in rats.

PMID- 18078739
TI  - Bone in idiopathic and symptomatic epilepsy.
AB  - OBJECTIVE: Bone mineral density (BMD) is reduced in epilepsy and may underlie the
      observed increased fracture rate. Non-ambulatory patients have reduced BMD,
      although, it is not clear if normally weight bearing ambulatory patients are
      similarly vulnerable. DESIGN: Cross-sectional study examining age- and gender
      specific z-score total bone mineral density (z-BMD) in 116 normally ambulatory
      children with epilepsy between ages 6 and 18 years (79 idiopathic epilepsy and 37
      symptomatic epilepsy) were compared to 36 healthy controls. RESULTS: Both
      idiopathic and symptomatic epilepsies were associated with lower z-BMD (0.38+/-1
      and 0.17+/-1, respectively) compared to controls (0.52+/-0.76). For both groups
      patients with generalized seizures had lower z-BMD than those with partial
      seizures. Symptomatic generalized epilepsy was associated with the lowest z-BMD (
      0.15+/-1.1) compared to controls (p < 0.05). Increasing duration of symptomatic
      epilepsy, but not idiopathic epilepsy, was associated with lower z-BMD
      (correlation coefficient = 0.1; p < 0.01). CONCLUSIONS: Both idiopathic and
      symptomatic epilepsy are associated with reduced BMD. Those with symptomatic
      epilepsy, particularly symptomatic generalized epilepsy, had the greatest
      reduction in BMD despite normal weight bearing and ambulation. These data
      suggests that BMD is reduced in epilepsy beyond what can be explained by lack of
      ambulation and may underlie the vulnerability to fractures.

PMID- 18078740
TI  - Intracranial EEG findings in patients with lesional lateral temporal lobe
      epilepsy.
AB  - PURPOSE: Intracranial EEG in patients with lesional lateral temporal lobe
      epilepsy is rarely reported. Therefore, the number of patients with seizures
      arising independently from ipsilateral mesial structures or contralateral
      hemisphere has not been clarified. We analyzed the intracranial EEG of cases with
      localized lesion in the lateral temporal cortex. METHODS: We studied 15 patients
      who satisfied the following criteria: (1) MRI depicted a lesion less than 4cm in
      diameter located lateral to the collateral sulcus and at least 3cm posterior to
      the temporal pole; (2) intracranial EEG with electrodes placed on bilateral
      temporal lobes captured at least one complex partial seizure; and (3)
      postoperative follow-up period of 2 years or longer. The mean age of seizure
      onset was 16.6 years (range, 11-25) and that at surgery was 26.7 years (range, 16
      36). RESULTS: A total of 147 complex partial seizures, 51 simple partial
      seizures, 16 secondarily generalized seizures, and over 80 subclinical seizures
      were recorded. On the lesional side, many clinical seizures were recorded from
      the lateral cortex. Independent of the lateral temporal onset seizures, ictal
      discharges originating from the mesial temporal structures were recorded in 7 of
      15 patients (47%). Moreover, onset of ictal discharges from the contralateral
      temporal lobe was recorded in 7 of 15 patients (47%). Interictal spikes from
      ipsilateral mesial structures were recorded in all patients. The presence of
      ipsilateral mesial onset seizures was not associated with hippocampal neuron
      losses. CONCLUSION: Intracranial EEG analysis revealed that approximately one
      half of the patients with structural lesions in the lateral cortex showed
      independent epileptogenic areas in ipsilateral mesial structures. Although ictal
      discharges originating from the contralateral temporal lobe were recorded in a
      half of these patients, this finding does not constitute a contraindication of
      resective surgery. Interictal spike is not an indicator of whether mesial
      structures should be resected.

PMID- 18078741
TI  - Fibroblasts from non-healing human chronic wounds show decreased expression of
      beta ig-h3, a TGF-beta inducible protein.
AB  - BACKGROUND: Increasing evidence shows persistent phenotypic alterations in
      fibroblasts from non-healing human chronic wounds, which may result in faulty
      extracellular matrix deposition and keratinocyte migration. We have previously
      shown that these cells are characterized by morphological changes, low
      proliferative potential and unresponsiveness to TGF-beta1, and down regulated
      phosphorylation of Smad 2/3 and p42/44 MAPK from decreased expression of the TGF
      beta type II receptor. OBJECTIVE: To identify genes and proteins that may be
      differentially expressed in chronic wounds and their cultured fibroblasts.
      METHODS: Differential display analysis with 120 random primer sets was used in
      fibroblasts from human venous ulcers and acute wounds created on the ipsilateral
      thighs of the same patients. Positive differential results were confirmed by RT
      PCR. Immunohistochemistry of cultured fibroblasts and tissues was used to
      determine the expression of differentially expressed proteins. RESULTS: A total
      of 16 differentially expressed genes were identified and cloned. The only
      candidate gene that was differentially expressed in all patients and confirmed by
      repeated differential display testing and RT-PCR was beta ig-h3, a TGF-beta
      induced gene involved in cell adhesion, migration, and proliferation. Decreased
      expression of beta ig-h3 in chronic wounds and their fibroblasts was further
      confirmed by Western blot and immunostaining. CONCLUSION: These findings point to
      beta ig-h3 as an important gene characterizing the abnormal phenotype of chronic
      wound fibroblasts. Corrective measures to increase the expression of this protein
      might have therapeutic potential.

PMID- 18078742
TI  - Karoly Schaffer and his school: the birth of biological psychiatry in Hungary,
      1890-1940.
AB  - In the first third of the twentieth century, neuropathology seemed to offer the
      key to unlock the causes of psychiatric illness. Among the top centers devoted to
      the microscopic anatomy of the brain was that of Karoly Schaffer in Budapest.
      Schaffer, a pioneer in the histopathology of Tay-Sachs-Schaffer disease, was also
      a charismatic teacher, bringing forth a school of investigators in
      psychopathology. Among them was Laszlo Meduna, who originated convulsive therapy.
      Despite the importance of the Schaffer school, it is almost unknown outside of
      Hungary, largely the result of the introduction of neurophysiological,
      neurochemical and molecular genetic methods that distracted attention away from
      histopathological contributions in psychiatry after the Second World War. The
      microscopic study of the brain and its diseases seemed increasingly less
      important. The present biographical account of Karoly Schaffer and his school
      seeks to bring this important story in the early history of biological psychiatry
      to a wider audience and explain why it has since been forgotten.

PMID- 18078743
TI  - Release pattern and structural integrity of lysozyme encapsulated in core-sheath
      structured poly(DL-lactide) ultrafine fibers prepared by emulsion
      electrospinning.
AB  - The purpose of this study was to investigate the structural integrity,
      bioactivity and release patterns of lysozyme, as a model protein, encapsulated
      within the core-shell structured ultrafine fibers prepared by emulsion
      electrospinning. Electron microscopy and laser confocal scanning microscopy
      images demonstrated that the fibrous mats were very porous with integrally core
      shell structured, bead-free, and randomly arrayed fibers. This structural
      property can pronouncedly alleviate the initial burst release and improve the
      sustainability of ultrafine fiber-based releasing devices. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and size exclusion chromatography were used to
      assess the primary structure of lysozyme, indicating that the ultra-sonication
      and electrospinning did not cause any remarkable denaturation of protein, while
      the core-shell structured fibers protected the structural integrity of
      encapsulated protein during incubation in the medium. Fourier transform infrared
      analyses showed that the electrospinning process had much less effect on the
      secondary structure of protein than ultra-sonication. The bioactivity assay
      indicated around 16% of specific activity loss during the emulsification
      procedure, and the protective effect of the shell materials on the activity of
      encapsulated protein. In vitro degradation showed that the protein entrapment led
      to more significant mass loss and higher molecular weight reduction.

PMID- 18078744
TI  - A label-free biosensor based on gold nanoshell monolayers for monitoring
      biomolecular interactions in diluted whole blood.
AB  - Gold nanoshells (GNSs) were self-assembled on the surface of transparent glasses
      modified with 3-aminopropyltrimethoxysilane (APTES) to form GNS self-assembled
      monolayers (SAMs). Because the localized surface plasmon resonance (LSPR) of GNSs
      can be controlled in the near-infrared (NIR) region of the spectrum, where the
      optical transmission through tissue and whole blood is optimal, GNSs would be
      used as an effective signal transduction in whole blood. Accordingly, after
      modified with cystamine and biotin-NHS (N-hydroxy succinimide), GNS SAMs were
      used as a novel optical biosensor for real-time detection of streptavidin-biotin
      interactions in diluted human whole blood within short assay time, without any
      sample purification/separation. An UV-vis-NIR spectrophotometer was used to
      monitor the absorbance changes at 730 nm as a function of time for different
      concentrations of streptavidin in 20% whole blood, and the results showed that
      the biosensor displayed low detection limit of approximately 3 microg/mL and wide
      dynamic range of approximately 3-50 microg/mL. This approach provides an
      opportunity to construct LSPR biosensor for protein sensing and cellular analysis
      in diluted whole blood.

PMID- 18078745
TI  - An in situ electrochemical surface plasmon resonance immunosensor with
      polypyrrole propylic acid film: comparison between SPR and electrochemical
      responses from polymer formation to protein immunosensing.
AB  - A novel in situ electrochemical surface plasmon resonance (EC-SPR) immunosensor
      is presented in this paper. The EC-SPR measurement can be used to in situ monitor
      the polymer formation, probe immobilization, antigen-antibody interaction and
      protein immunosensing process. A sandwich immunosensor based on permeable
      polypyrrole propylic acid (PPA) film is constructed using mouse IgG as a model
      analyte. The results show that the introduction of capture antibody conjugated
      enzyme not only enhances the current responses but also increases the SPR angle
      shift. The calibration curves of electrochemical (EC) and surface plasmon
      resonance (SPR) measurement exhibit a similar dependence on the bulk
      concentration of antigen. An approximate linear relationship can be obtained by
      plotting the data in semi-logarithmic reference frame. Compared with SPR, EC
      shows higher sensitivity with prolonged time. The in situ EC-SPR immunosensor
      described herein could have important potentials for diagnostics and medicine
      applications.

PMID- 18078746
TI  - Synthesis and analysis of a fluorinated product analogue as an inhibitor for 1
      deoxy-D-xylulose 5-phosphate reductoisomerase.
AB  - 1-deoxy-D-xylulose 5-phosphate (DXP) reductoisomerase (DXR) is an NADPH-dependent
      enzyme catalyzing the rearrangement and reduction of DXP to methyl-D-erythritol 4
      phosphate (MEP). Two mechanisms for this enzymatic reaction have been proposed,
      involving either an alpha-ketol rearrangement or a retroaldol/aldol
      rearrangement. In this study, a fluorinated product analogue, FCH(2)-MEP, was
      synthesized as a possible mechanism-based inactivator for DXR if the
      retroaldol/aldol mechanism is operative. FCH(2)-MEP was found to be a weak
      competitive inhibitor, and thus was unable to discriminate between the
      mechanisms. This result is due to the inability of the targeted enzyme, DXR, to
      oxidize FCH(2)-MEP to the aldehyde intermediate that is common to both
      mechanisms. While FCH(2)-MEP failed to act as a mechanism-based inactivator, the
      insight gained from this study will assist in the future design of inhibitors of
      DXR.

PMID- 18078747
TI  - A novel bicyclic hexapeptide, RA-XVIII, from Rubia cordifolia: structure, semi
      synthesis, and cytotoxicity.
AB  - A new bicyclic peptide of RA-series, RA-XVIII (3), was isolated from the roots of
      Rubia cordifolia L. Its structure was established to be a hydroxylated derivative
      of RA-VII by the semi-synthesis of 3 from deoxybouvardin, and its cytotoxicity
      against P-388 cells was 0.012 microg/mL.

PMID- 18078748
TI  - Synthesis and biological activity of novel peptide mimetics as melanocortin
      receptor agonists.
AB  - A series of novel peptidomimetic analogs was prepared containing cyclohexyl,
      phenyl, or heterocyclic groups to ostensibly orient the guanidine or mimic of an
      arginine in a putative melanocortin receptor ligand pharmacophore. Some binding
      affinity at the melanocortin receptors MC(3) and MC(4) was noted. In silico
      docking also indicated that the relative positions of the hydrogen-bonding sites
      and hydrophobic regions of the compounds are reasonably well matched to the
      receptor-binding site. This may present a lead entry into a selective series of
      MC(4)R agonists.

PMID- 18078750
TI  - Thiol-based angiotensin-converting enzyme 2 inhibitors: P1 modifications for the
      exploration of the S1 subsite.
AB  - Screening of a metalloprotease library led to the identification of a thiol-based
      dual ACE/NEP inhibitor as a potent ACE2 inhibitor. Modifications of the P(1)
      benzyl moiety led to improvements in ACE2 potency as well as to increased
      selectivity versus ACE and NEP.

PMID- 18078749
TI  - Synthesis and structure-activity relationship studies of tyrosine-based
      antagonists at the human P2X7 receptor.
AB  - Analogues of the P2X(7) receptor antagonist KN-62, modified at the piperazine and
      arylsulfonyl groups, were synthesized and assayed at the human P2X(7) receptor
      for inhibition of BzATP-induced effects, that is, uptake of a fluorescent dye
      (ethidium bromide) in stably transfected HEK293 cells and IL-1beta release in
      differentiated THP-1 cells. Substitution of the arylsulfonyl moiety with a nitro
      group increased antagonistic potency relative to methyl substitution, such that
      compound 21 was slightly more potent than KN-62. Substitution with D-tyrosine in
      36 and sterically bulky tyrosyl 2,6-dimethyl groups [corrected] in 9 enhanced
      antagonistic potency.

PMID- 18078751
TI  - Design and synthesis of substituted 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5
      a]pyrazine-2-carboxamides, novel HIV-1 integrase inhibitors.
AB  - A series of 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides was
      synthesized and tested for their inhibition of HIV-1 integrase catalytic activity
      and HIV-1 replication in cells. Structure-activity studies around lead compound 5
      indicated that a coplanar relationship of metal-binding heteroatoms provides
      optimal binding to the integrase active site. Identification of potency-enhancing
      substituents and adjustments in lipophilicity provided 17b which inhibits
      integrase-catalyzed strand transfer with an IC(50) value of 74 nM and inhibits
      HIV-1 replication in cell culture in the presence of 50% normal human serum with
      an IC(95) value of 63 nM.

PMID- 18078752
TI  - Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase
      inhibitors and cytodifferentiating agents.
AB  - A series of substituted benzoylamino-2-[(4-benzyl)thio]-1,3,4-thiadiazoles has
      been discovered as potent Abl tyrosine kinase inhibitors. Molecular docking
      simulations on the Abl tyrosine kinase were conducted in order to rationalize the
      SAR of the synthesized inhibitors. The most active compound identified from the
      enzymatic screening (6a) showed interesting inhibitory activity on Imatinib
      sensitive murine myeloid 3B clone and Bcr-Abl-independent Imatinib-resistant
      leukemia cells. Surprisingly, 6a was also proved to act as differentiating
      inducers in human promyelocytic leukemia cells (HL-60).

PMID- 18078753
TI  - Design and characterization of mechanism-based inhibitors for the tyrosine
      aminomutase SgTAM.
AB  - The synthesis and evaluation of two classes of inhibitors for SgTAM, a 4
      methylideneimidazole-5-one (MIO) containing tyrosine aminomutase, are described.
      A mechanism-based strategy was used to design analogs that mimic the substrate or
      product of the reaction and form covalent interactions with the enzyme through
      the MIO prosthetic group. The analogs were characterized by measuring inhibition
      constants and X-ray crystallographic structural analysis of the co-complexes
      bound to the aminomutase, SgTAM.

PMID- 18078754
TI  - Chondrotinase ABC enhances axonal regeneration across nerve gaps.
AB  - We evaluated the effects of chondroitinase ABC on axonal regeneration across
      peripheral nerve gaps. We compared axonal regeneration after 15-mm tibial nerve
      resection and repair with a silicone tube filled with type I collagen gel
      (negative control group), with a silicone tube filled with type I collagen gel
      containing chondroitinase ABC at three different concentrations (2.5 units/mL, 5
      units/mL, 10 units/mL) (chondroitinase ABC groups), and with an autologous nerve
      segment (nerve autograft group). Electrophysiological and histological
      assessments were carried out 12 weeks after surgery. In the electrophysiological
      study, compound muscle action potentials (CMAPs) and nerve conduction velocities
      (NCVs) were recorded in all groups except the negative control group. Although
      both CMAPs and NCVs were highest in the nerve autograft group, there were no
      significant differences among the three chondroitinase ABC groups in either
      parameter. Histological findings were consistent with electrophysiological
      results. Based on these findings, we conclude that topical injection of
      chondroitinase ABC can significantly increase the critical length of nerve gap
      repair by tubulization or artificial nerve placement.

PMID- 18078755
TI  - Adult medulloblastoma: clinical profile and treatment results of 18 patients.
AB  - The objective of this article is to examine the clinicoradiological features and
      surgical outcomes of adult patients (>16 years) with medulloblastoma. An attempt
      was made to identify the predictors of poor outcome and assess patterns of
      relapse and to compare these with pediatric medulloblastoma. Retrospective case
      record analyses were performed on 18 adults (>16 years) and 79 children (<16
      years) operated upon after January 1990, who had at least 5 years of follow-up.
      The following variables were assessed by bivariate analyses: age, location of the
      lesion, brainstem invasion, extent of excision and histological subtype.
      Statistical analysis was performed using chi-square test, Fischer's exact test
      and Student's t-test. Results revealed there was no gender preference. The tumor
      was located in the vermis in 12 patients (66.6%) and in the cerebellar hemisphere
      in six (16.6%). Calcification was observed in two cases (11.1%) and hydrocephalus
      was seen in six (33.3%). MRI evidence of brainstem infiltration was seen in three
      patients (16.6%). Total excision was achieved in 13 cases (72.2%), near total
      excision in four (22.2%) and subtotal excision in one. Major complications
      included fresh cranial nerve deficits in four patients (22.2%), hemiparesis and
      gait unsteadiness in three (16.6%), mutism in one and meningitis in two. All
      patients underwent adjuvant radiotherapy in the form of craniospinal irradiation
      with a posterior fossa boost. On follow-up, 11 patients (61.1%) were observed to
      have recurrence and all were located in the posterior fossa. All 11 subsequently
      underwent chemotherapy. Two patients had re-operation for residual/recurrent
      lesions causing raised intracranial symptoms. Five-year follow-up data showed
      that 10 patients (55.5%) were alive, five (27.7%) had died while three (16.6%)
      were lost to follow-up. In spite of recent advances in management, patients with
      medulloblastoma still have a poor prognosis. However, adults fared better than
      children. Vermian location had a better outcome in adults, but not in children.
      Desmoplastic variant histology was not observed to be a significant prognostic
      factor in the adult group while brain stem invasion carried a poor prognosis.

PMID- 18078756
TI  - Synthesis and antimycobacterial evaluation of newer 1-cyclopropyl-1,4-dihydro-6
      fluoro-7-(substituted secondary amino)-8-methoxy-5-(sub)-4-oxoquinoline-3
      carboxylic acids.
AB  - Thirty-four newer 1-cyclopropyl-1,4-dihydro-6-fluoro-7-(substituted secondary
      amino)-8-methoxy-5-(sub)-4-oxoquinoline-3-carboxylic acids were synthesized from
      1,2,3,4-tetrafluoro benzene and evaluated for in vitro and in vivo
      antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB),
      multi-drug resistant M. tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC(2))
      and also tested for the ability to inhibit the supercoiling activity of DNA
      gyrase. Among the synthesized compounds, 7-(1-(4-methoxybenzyl)-3,4,5,6,7,8
      hexahydroisoquinolin-2(1H)-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-5
      nitro-4-oxoquinoline-3-carboxylic acid (13n) was found to be the most active
      compound in vitro with MIC of 0.16 and 0.33 microM against MTB and MDR-TB,
      respectively. In the in vivo animal model 13n decreased the bacterial load in
      lung and spleen tissues with 2.54 and 2.92-log10 protections, respectively, at
      the dose of 50mg/kg body weight. Compound 13n also inhibited the supercoiling
      activity of mycobacterial DNA gyrase with IC(50) of 30.0 microg/ml.

PMID- 18078757
TI  - Synthesis, cytostatic and anti-HCV activity of 6-(N-substituted aminomethyl)-, 6
      (O-substituted hydroxymethyl)- and 6-(S-substituted sulfanylmethyl)purine
      nucleosides.
AB  - An efficient and facile synthesis of a large series of diverse 6-(N-substituted
      aminomethyl)-, 6-(O-substituted hydroxymethyl)- and 6-(S-substituted
      sulfanylmethyl)purine nucleosides (55 examples of both ribo- and 2'
      deoxyribonucleosides), aimed at identifying novel homologues of natural
      nucleosides, was developed. The key transformation involved nucleophilic
      substitutions of Tol-protected 6-(mesyloxymethyl)purine nucleosides by primary or
      secondary amines, alcoholates or thiolates. While the 2'-deoxyribonucleosides
      were inactive, the ribonucleosides exerted considerable cytostatic effects and
      some anti-HCV activity with low selectivity.

PMID- 18078758
TI  - Anti-Plasmodium activity of tetrazolium salts.
AB  - We have previously reported that sulfated cyclodextrins inhibit the invasion of
      Plasmodium merozoites by interacting with receptors present on the surface of
      erythrocytes. The observation that tetrazolium salts formed stable complexes with
      the inhibitory sulfated cyclodextrins suggested that tetrazolium salts might have
      anti-Plasmodium activity as well. Evaluation of commercially available
      tetrazolium salts indicated that some were active in the low nanomolar range and
      showed specificity in their inhibition of Plasmodium. Synthesis of a further 54
      structures allowed us to determine that activity results from an aromatic
      component attached to the tetrazolium carbon atom (R1) and its size is not
      critical to the activity of the compound. Nitro modifications of active compounds
      are poorly tolerated, however, the presence of halogen atoms on aromatic groups
      attached to the nitrogen atoms of the tetrazolium ring (R2 and R3) has little
      effect on activity. Methoxy groups are tolerated on R2 and R3 components;
      however, they are disruptive on the R1 component. The overall results suggest
      that the R1 component is interacting with a specific hydrophobic environment and
      the R2 and R3 components are less constrained. The activity of these compounds in
      several human and mouse Plasmodium cultures suggests that the compounds interact
      with a component of the parasite that is both essential and conserved.

PMID- 18078760
TI  - Parallel synthesis of a series of potentially brain penetrant aminoalkyl
      benzoimidazoles.
AB  - Alpha7 agonists were identified via GOLD (CCDC) docking in the putative agonist
      binding site of an alpha7 homology model and a series of aminoalkyl
      benzoimidazoles was synthesised to obtain potentially brain penetrant drugs. The
      array was prepared starting from the reaction of ortho-fluoronitrobenzenes with a
      selection of diamines, followed by reduction of the nitro group to obtain a
      series of monoalkylated phenylene diamines. N,N'-Carbonyldiimidazole (CDI)
      mediated acylation, followed by a parallel automated work-up procedure, afforded
      the monoacylated phenylenediamines which were cyclised under acidic conditions.
      Parallel work-up and purification afforded the array products in good yields and
      purities with a robust parallel methodology which will be useful for other
      libraries. Screening for alpha7 activity revealed compounds with agonist activity
      for the receptor.

PMID- 18078759
TI  - Synthesis and solution conformation studies of 3-substituted uridine and
      pseudouridine derivatives.
AB  - A series of 3-substituted uridine and pseudouridine derivatives, based on the
      naturally occurring 3-(3-amino-3-carboxypropyl) modification, were synthesized.
      Their aqueous solution conformations were determined by using circular dichroism
      and NMR spectroscopy. Functional group composition and chain length were shown to
      have only a subtle influence on the distribution of syn/anti conformations of the
      modified nucleosides. The dominating factor appears to be the glycosidic linkage
      (C- vs. N-glycoside) in determining the nucleoside conformation.

PMID- 18078761
TI  - Bornyl (3,4,5-trihydroxy)-cinnamate--an optimized human neutrophil elastase
      inhibitor designed by free energy calculations.
AB  - Human neutrophil elastase (HNE), a serine protease, is involved in the regulation
      of inflammatory processes and controlled by endogenous proteinase inhibitors.
      Abnormally high levels of HNE can cause degradation of healthy tissues
      contributing to inflammatory diseases such as rheumatoid arthritis, and also
      psoriasis and delayed wound healing. In continuation of our research on HNE
      inhibitors we have used the recently developed binding mode model for a group of
      cinnamic acid derivative elastase inhibitors and created bornyl (3,4,5
      trihydroxy)-cinnamate. This ligand exhibited improved binding affinity predicted
      by means of free energy calculations. An organic synthesis scheme for the ligand
      was developed and its inhibitory activity was tested toward the isolated enzyme.
      Its IC(50) value was found to be three times lower than that of similar
      compounds, which is in line with the computational result showing the high
      potential of free energy calculations as a tool in drug development.

PMID- 18078762
TI  - Effect of ischemic postconditioning in adult valve replacement.
AB  - OBJECTIVE: Ischemic postconditioning (POC) by brief episodes of ischemia
      performed just at the time of reperfusion can reduce infarct size in animal
      models and clinical settings of percutaneous coronary intervention. However, the
      clinical applicability of postconditioning in cardiac surgery remains to be
      determined. We investigated the effect of postconditioning on myocardial
      protection in patients undergoing valve replacement. METHODS: Fifty adult
      patients scheduled for elective valve replacement under cold blood cardioplegic
      arrest were randomly assigned to postconditioning (n=25) or control treatment
      (n=25). Postconditioning was performed by three cycles of 30s ischemia and 30s
      reperfusion using aortic re-clamping and de-clamping started 30s after
      cardioplegic arrest. The creatine kinase-MB, troponin I, transcardiac release of
      lactate were assayed. Measurements of clinical results were recorded during the
      study. RESULTS: The types of procedure, age, bypass and aortic cross-clamping
      times were similar in both groups. The postoperative peak creatine kinase-MB was
      lower after aortic de-clamping in the postconditioning patients compared with the
      control group (66+/-24 U/l vs 84+/-20 U/l, p=0.02) and peak cTnI was similar in
      both groups. The required inotropes were reduced in postconditioning group
      compared with the control group (2.3+/-1.8 vs 4.1+/-2.2 microg/min/kg, p=0.03).
      There were reduction trends with regard to transcardiac release of lactate in
      postconditioning group compared with the control group (0.10+/-0.17 mmol/l vs
      0.24+/-0.16 mmol/l, p=0.08). The transcardiac neutrophil count during reperfusion
      was less in POC group compared with the control group (7.8+/-6.3% vs 14.0+/-8.7%,
      p=0.04). CONCLUSIONS: The present study demonstrated that postconditioning may
      protect adult myocardium undergoing cold blood cardioplegic arrest. These data
      support the need for a further clinical trial of postconditioning in cardiac
      surgery.

PMID- 18078763
TI  - In vitro inhibition of sole aquabirnavirus by Senegalese sole Mx.
AB  - Senegalese sole, Solea senegalensis, is a flat fish of growing interest in
      European aquaculture. In its culture viral infections are constant threats, thus
      understanding antiviral defences is a key factor for a successful industry. Mx
      proteins are IFN-induced proteins widespread in eukaryotes; however, their
      antiviral activity is unclear and the results variable among species. Therefore
      assessment of the putative Mx antiviral activity in each species is of interest.
      Our group has recently cloned the Senegalese sole Mx (SsMx) cDNA and in this
      study its antiviral activity was assessed by infecting CHSE-214 cells expressing
      recombinant SsMx, with sole aquabirnavirus. The antiviral activity against this
      pathogen was demonstrated by reduction in induced cytopathic effects, reduction
      in virus yield and decrease in viral transcripts. These findings contribute to
      our understanding of fish antiviral mechanisms and open the possibility of using
      this protein as a tool for fighting viral infections in aquaculture.

PMID- 18078764
TI  - Extraarticular variants of the long head of the biceps brachii: a reminder of
      embryology.
AB  - Developmental anomalies of the long head of the biceps tendon are rare and have
      been described in the literature mainly dealing with anatomy and embryology.
      Because most basic embryologic research on this topic was conducted before 1966,
      a literature search was performed from archived anatomy textbooks and manuscript
      references. These data were compared with the scarce case descriptions of
      developmental anomalies of the long head of the biceps tendon. An additional case
      illustration from our own experience was provided. From the literature, it
      appears that during the embryologic phase of development, a staged migration of
      the long head of the biceps tendon occurs from a position between the fibrous
      capsule and synovial layer to an intraarticular position. Recent anatomic and
      arthroscopic case reports have shown that interruption of this migration can
      occur in any of these stages. Given the recent increase in arthroscopic shoulder
      surgery, anomalies of the long head of the biceps tendon will be encountered more
      frequently. Knowledge of their existence and origin can help in evaluating
      unexpected anatomic variations or the absence of the biceps tendon in
      preoperative medical imaging or during an arthroscopic procedure.

PMID- 18078765
TI  - Cyclic AMP-dependent proteolysis of GATA-6 expressed on the intracellular
      membrane.
AB  - Cyclic AMP-dependent proteolysis of GATA-6 was characterized by fusing GATA-6
      with the carboxyl-terminal membrane domain of SREBP-2. When the fusion protein
      was stably expressed in CHO-K1 cells, it was recovered in the ER membrane. This
      protein was processed in a similar manner to SREBP-2 upon cholesterol starvation,
      and the GATA-6 moiety moved into the nucleus. The GATA-6 moiety on the membrane
      became undetectable in the presence of dbcAMP or cholera toxin. However, H-89, K
      252a, MG115 and lactacystin inhibited this decrease, suggesting that the
      cytoplasmic GATA-6 moiety of the fusion protein was degraded by proteasomes
      though A-kinase upon elevation of the cellular cAMP concentration.

PMID- 18078766
TI  - Celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma
      cell line MG-63 via down-regulation of PI3K/Akt.
AB  - Cyclooxygenase-2 (COX-2), involved in the inhibition of apoptosis and, the
      potentiation of cell growth, is frequently overexpressed in human malignancies
      including osteosarcoma (OS). We have attempted to identify the anti-proliferation
      of celecoxib, a selective COX-2 inhibitor, and the combination of celecoxib and
      cisplatin in MG-63 cells, and to explore the potential molecular mechanisms
      involved. MG-63 cells were treated with the combination of celecoxib and
      cisplatin or either agent alone for 48h in serum-supplemented medium. Celecoxib
      caused G1 phase arrest and significantly inhibited cell growth, as well as
      potentiating cisplatin-induced apoptosis. The effect was dose-dependent, and
      apoptotic changes such as DNA fragments and apoptotic bodies were observed.
      However, downregulation of COX-2 did not occur in cells treated with celecoxib.
      Phosphoinositide-3-kinase (PI3K)/Akt, survivin, bcl-2 were significantly
      downregulated in cells treated with the combination of celecoxib and cisplatin,
      and decreased survivin and bcl-2 levels were found in cells with wortmannin, a
      specific PI3K inhibitor. Moreover, the decreased expressions of procaspase-9,
      procaspase-3 and cleaved PARP-1 were detected by Western blot analysis.
      Therefore, celecoxib exerts its anti-tumor activities through COX-2-independent
      mechanisms, which may be PI3K/Akt-dependent, and survivin and bcl-2-related. PI3K
      may be at the center of the celecoxib effects, which play an essential role in
      the regulation of survivin and Bcl-2.

PMID- 18078767
TI  - Mycoplasma bovis and otitis in dairy calves in the United Kingdom.
AB  - Signs of severe otitis media in 20% of dairy calves on one farm were associated
      with Mycoplasma bovis infection, based on isolation from the external ear canal
      and nares. Affected calves seroconverted to M. bovis and no other significant
      bacteria were isolated. Infection was considered likely to have originated from
      cows in the milking herd based on evidence of seroconversion and detection of
      infection in a milk sample. M. bovis infection should be considered when
      investigating otitis problems in calves.

PMID- 18078768
TI  - Partial sequencing and expression of genes involved in glucose metabolism in
      adipose tissues and skeletal muscle of healthy cats.
AB  - Impaired insulin sensitivity is increasingly recognised in cats, but sequences of
      genes involved in insulin-signalling are largely undetermined in this species. In
      this study, extended feline mRNA sequences were determined for the adiponectin,
      glucose transporter-1 (GLUT1), GLUT4, peroxisome proliferative activated receptor
      gamma1 (PPARgamma1), PPARgamma2, plasminogen activator inhibitor-1 (PAI-1),
      monocyte chemoattractant protein-1 (MCP-1) and insulin receptor genes. Conserved
      dog-specific primers identified from human-dog mRNA alignments were used to
      amplify feline cDNA in the polymerase chain reaction (PCR). The feline sequences
      determined by this method were used to design feline-specific primers suitable
      for real-time PCR for quantification of gene expression in insulin sensitive
      tissues of healthy cats. Partial sequences of feline mRNAs had 86-95% identity
      with dog and human genes. Expression of adiponectin, GLUT1, GLUT4, PPARgamma1,
      PPARgamma2, PAI-1 and insulin receptor mRNA was detected and quantified in
      subcutaneous and visceral fat and skeletal muscle, whereas MCP-1 mRNA was
      detected in adipose tissue but not in skeletal muscle. Further characterisation
      of genes related to glucose metabolism in cats will provide additional insights
      into insulin-signalling mechanisms in this species.

PMID- 18078769
TI  - Influence of a chronic myositis on rat spinal field potentials evoked by TTX
      resistant unmyelinated skin and muscle afferents.
AB  - A recent study of our group has shown that in the segments L4 and L5 of the rat,
      the synaptic field potentials (SFPs) evoked by tetrodotoxin-resistant (TTX-r,
      presumably nociceptive) muscle afferents differ in size and peak location from
      those of cutaneous afferents from the same body region [Lambertz D, Hoheisel U,
      Mense S. Distribution of synaptic field potentials induced by TTX-resistant skin
      and muscle afferents in rat segment L4 and L5. Neurosci Lett 2006;409:14-8].
      Here, we investigated the influence of a muscle inflammation on the distribution
      of SFPs of TTX-r afferent fibres from muscle and skin in the thoracic and lumbar
      spinal cord. During a TTX block of the dorsal roots L3-L6, a skin nerve (sural,
      SU) or a muscle nerve (gastrocnemius-soleus, GS) were electrically stimulated at
      an intensity supramaximal for unmyelinated afferents and the SFPs recorded with
      tungsten microelectrodes. In control (non-inflamed) rats, the largest SFPs evoked
      by TTX-r GS afferents were recorded in laminae IV-VI with a maximum in segment
      L4, whereas the largest SU-induced SFPs were more superficially located with a
      maximum in L3. In chronic myositis animals, SFPs induced by GS TTX-r fibres
      exhibited significant decreases in lamina IV-VI of Th 12 and L5 as well as in
      lamina VII of L5. In contrast, SFPs evoked by SU TTX-r afferents showed
      significant increases in lamina IV-VI in L1 and in lamina VII in L4. The results
      demonstrate that a chronic myositis has a strong influence also on the synaptic
      effects of nociceptive afferents from the skin, which may explain the subjective
      cutaneous sensations during a pathological alteration of muscle.

PMID- 18078770
TI  - Accurate measurements of small J coupling constants under inhomogeneous fields
      via intermolecular multiple-quantum coherences.
AB  - Two new NMR pulse sequences, based on intermolecular multiple-quantum coherences
      (iMQCs), were developed to obtain apparent J coupling constants with a scaling
      factor from one to infinity relative to the conventional J coupling constants.
      Here the apparent J coupling constants were defined as apparent peak separations
      in unit of Hz in a reconstructed spectrum for a coupled spin system. Except for
      the adjustable scaling factor for apparent J coupling constants, the sequences
      hold the advantage of high acquisition efficiency, and retain the spectral
      information such as chemical shifts, multiplet patterns, and relative peak areas
      under inhomogeneous fields. For spin systems with small scalar coupling
      constants, well-resolved J-spectra can be achieved by selecting a proper scaling
      factor. Theoretical predictions are in good agreement with simulation results and
      experimental observations.

PMID- 18078771
TI  - Sensitivity-enhanced IPAP-SOFAST-HMQC for fast-pulsing 2D NMR with reduced
      radiofrequency load.
AB  - The SOFAST-HMQC experiment [P. Schanda, B. Brutscher, Very fast two-dimensional
      NMR spectroscopy for real-time investigation of dynamic events in proteins on the
      time scale of seconds, J. Am. Chem. Soc. 127 (2005) 8014-8015] allows recording
      two-dimensional correlation spectra of macromolecules such as proteins in only a
      few seconds acquisition time. To achieve the highest possible sensitivity, SOFAST
      HMQC experiments are preferably performed on high-field NMR spectrometers
      equipped with cryogenically cooled probes. The duty cycle of over 80% in fast
      pulsing SOFAST-HMQC experiments, however, may cause problems when using a
      cryogenic probe. Here we introduce SE-IPAP-SOFAST-HMQC, a new pulse sequence that
      provides comparable sensitivity to standard SOFAST-HMQC, while avoiding
      heteronuclear decoupling during (1)H detection, and thus significantly reducing
      the radiofrequency load of the probe during the experiment. The experiment is
      also attractive for fast and sensitive measurement of heteronuclear one-bond spin
      coupling constants.

PMID- 18078772
TI  - Spin-labeled gel for the production of radical-free dynamic nuclear polarization
      enhanced molecules for NMR spectroscopy and imaging.
AB  - Dynamic nuclear polarization (DNP) has recently received much attention as a
      viable approach to enhance the sensitivity of nuclear magnetic resonance (NMR)
      spectroscopy and the contrast of magnetic resonance imaging (MRI), where the
      significantly higher electron spin polarization of stable radicals is transferred
      to nuclear spins. In order to apply DNP-enhanced NMR and MRI signal to biological
      and in vivo systems, it is crucial to obtain highly polarized solution samples at
      ambient temperatures. As stable radicals are employed as the source for the DNP
      polarization transfer, it is also crucial that the highly polarized sample lacks
      residual radical concentration because the polarized molecules will be introduced
      to a biological system that will be sensitive to the presence of radicals. We
      developed an agarose-based porous media that is covalently spin-labeled with
      stable radicals. The loading of solvent accessible radical is sufficiently high
      and their mobility approximates that in solution, which ensures high efficiency
      for Overhauser mechanism induced DNP without physically releasing any measurable
      radical into the solution. Under ambient conditions at 0.35 T magnetic field, we
      measure the DNP enhancement efficiency of (1)H signal of stagnant and
      continuously flowing water utilizing immobilized stable nitroxide radicals that
      contain two or three ESR hyperfine splitting lines and compare them to the
      performance of freely dissolved radicals.

PMID- 18078773
TI  - Methods for a prompt and reliable laboratory diagnosis of Pompe disease: report
      from an international consensus meeting.
AB  - Pompe disease is an autosomal recessive disorder of glycogen metabolism caused by
      a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). It presents at
      any age, with variable rates of progression ranging from a rapidly progressive
      course, often fatal by one-year of age, to a more slowly, but nevertheless
      relentlessly progressive course, resulting in significant morbidity and premature
      mortality. In infants, early initiation of enzyme replacement therapy is needed
      to gain the maximum therapeutic benefit, underscoring the need for early
      diagnosis. Several new methods for measuring GAA activity have been developed.
      The Pompe Disease Diagnostic Working Group met to review data generated using the
      new methods, and to establish a consensus regarding the application of the
      methods for the laboratory diagnosis of Pompe disease. Skin fibroblasts and
      muscle biopsy have traditionally been the samples of choice for measuring GAA
      activity. However, new methods using blood samples are rapidly becoming adopted
      because of their speed and convenience. Measuring GAA activity in blood samples
      should be performed under acidic conditions (pH 3.8-4.0), using up to 2 mM of the
      synthetic substrate 4-methylumbelliferyl-alpha-D-glucoside or glycogen (50
      mg/mL), in the presence of acarbose (3-9 microM) to inhibit the isoenzyme maltase
      glucoamylase. The activity of a reference enzyme should also be measured to
      confirm the quality of the sample. A second test should be done to support the
      diagnosis of Pompe disease until a program for external quality assurance and
      proficiency testing of the enzymatic diagnosis in blood is established.

PMID- 18078775
TI  - Detection of hepatitis G virus envelope protein E2 antibody in blood donors.

PMID- 18078774
TI  - Mechanism whereby nitric oxide (NO) infused chronically intrauterine in ewes is
      antiluteolytic rather than being luteolytic.
AB  - Nitric oxide (NO) has been reported to be luteolytic in vitro and in vivo in
      cows. However, an NO donor reversed PGF2alpha-induced inhibition of rat luteal
      progesterone secretion in vitro and an NO donor or endothelin-1 stimulated bovine
      luteal tissue secretion of prostaglandins E (PGE; PGE1, PGE2) in vitro without
      affecting progesterone or PGF2alpha secretion. In addition, chronic infusion of
      an NO donor into the interstitial tissue of the ovarian vascular pedicle adjacent
      the luteal-containing ovary prevented the decline in circulating progesterone,
      while a nitric oxide synthase (NOS) inhibitor did not affect luteolysis. The
      objective of this experiment was to determine whether an NO donor or NOS
      inhibitor infused chronically intrauterine adjacent to the luteal-containing
      ovary during the ovine estrous cycle was luteolytic or antiluteolytic. Ewes were
      treated either with vehicle (N=5), diethylenetriamine (DETA-control for
      DETANONOate; N=5), (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium
      1,2-diolate (DETANONOate-long acting NO donor; N=6), l-arginine (N=5), l-nitro
      arginine methyl ester (l-NAME-NOS inhibitor; N=6), or NG-monomethyl-l-arginine
      acetate (l-NMMA; NOS inhibitor; N=5) every 6h from 2400h (0h) on day 8 through
      1800h on day 18 of the estrous cycle. Jugular venous blood and inferior vena cava
      plasma via a saphenous vein cathether 5cm anterior to the juncture of the ovarian
      vein and inferior vena cava were collected every 6h for analysis for progesterone
      and PGF2alpha and PGE, respectively, by RIA. Corpora lutea were collected at
      1800h on day 18 and weighed. Weights of corpora lutea were heavier (P< or =0.05)
      in DETANONOate-treated ewes when compared to vehicle, DETA, l-arginine, l-NAME,
      or l-NMMA-treated ewes, l-arginine luteal weights were heavier than vehicle,
      DETA, l-arginine, l-NAME, or l-NMMA-treated ewes, and luteal weights of vehicle,
      DETA, l-NAME, or l-NMMA-treated ewes did not differ amongst each other (P> or
      =0.05). Profiles of progesterone in jugular venous blood on days 8-18 differed
      (P< or =0.05) in DETANONOate-treated ewes when compared to vehicle, DETA, l
      arginine, l-NMMA or l-NAME-treated ewes, which did not differ (P> or =0.05)
      amongst each other. The PGE:PGF2alpha ratio profile in inferior vena cava plasma
      of DETANONOate-treated ewes was increased (P< or =0.05) when compared to all
      other treatment groups. In a second experiment, conversion of [3H PGE2] to [3H
      PGF2alpha] by day 15 ovine caruncular endometrium in vitro was determined in
      vehicle, DETA, or DETANONOate-treatment groups. Conversion of [3H PGE2] to [3H
      PGF2alpha] was decreased (P< or =0.05) only by DETANONOate. It is concluded that
      NO is not luteolytic during the ovine estrous cycle, but may instead be
      antiluteolytic and prevent luteolysis by altering the PGE:PGF2alpha ratio
      secreted by the uterus.

PMID- 18078776
TI  - Fas/Fas-L expression, apoptosis and low proliferative response are associated
      with heart failure in patients with chronic Chagas' disease.
AB  - Chagas' disease affects 16-18 million patients in South America and heart
      involvement is the major cause of morbidity and mortality. Heart failure is the
      most severe clinical manifestation of the chronic phase of infection with
      Trypanosoma cruzi. The intensity and nature of the immune response is associated
      with the clinical outcome of the disease. In murine models, a low proliferative
      response and T-cell apoptosis have been observed during acute infection. In the
      present study the immune response of patients in the chronic phase of infection
      was analyzed. Patients were divided into: (a) asymptomatic, i.e., without
      involvement of the heart or digestive system; and (b) with heart failure.
      Patients with heart failure presented a significantly lower peripheral blood
      mononuclear cell (PBMC) proliferative response to T. cruzi antigens compared to
      asymptomatic patients. This low response was associated with antigen-induced
      apoptosis. Apoptosis of PBMC and a low proliferative response were also
      associated with double Fas/Fas-L expression and high production of TNF-alpha, a
      cytokine known to induce programmed cell death. These results suggest that
      apoptosis of PBMC, probably triggered by double expression of Fas/Fas-L and TNF
      alpha, is implicated in the immune regulatory mechanism during the chronic phase
      of Chagas' disease.

PMID- 18078777
TI  - Ultrasound promoted copper-, ligand- and amine-free synthesis of
      benzo[b]furans/nitro benzo[b]furans via Sonogashira coupling-5-endo-dig
      cyclization.
AB  - This method describes the results of the optimized conditions for the one-pot
      synthesis of benzo[b]furans/nitro benzo[b]furans via Sonogashira coupling-5-endo
      dig-cyclization under ultrasonic irradiation at ambient temperature in the
      absence of copper, ligand and amine. The protocol tolerates wide range of
      functional groups present in both the coupling components, especially base labile
      nitro group was not affected under these mild conditions giving excellent yields
      of the nitro benzo[b]furans. The formation of Pd(0) nanoparticles as the active
      species has been shown by TEM analysis and the unique role of ultrasound in
      promoting the total sonochemical protocol has been substantiated by way of
      control experiments.

PMID- 18078779
TI  - Diverse and conserved roles of CLE peptides.
AB  - The function of plant CLAVATA3 (CLV3)/ENDOSPERM SURROUNDING REGION (ESR) (CLE)
      peptides in shoot meristem differentiation has been expanded in recent years to
      implicate roles in root growth and vascular development among different CLE
      family members. Recent evidence suggests that nematode pathogens within plant
      roots secrete ligand mimics of plant CLE peptides to modify selected host cells
      into multinucleate feeding sites. This discovery demonstrated an unprecedented
      adaptation of an animal gene product to functionally mimic a plant peptide
      involved in cellular signaling for parasitic benefit. This review highlights the
      diverse and conserved role of CLE peptides in these different contexts.

PMID- 18078778
TI  - Detecting impossible changes in infancy: a three-system account.
AB  - Can infants detect that an object has magically disappeared, broken apart or
      changed color while briefly hidden? Recent research suggests that infants detect
      some but not other 'impossible' changes; and that various contextual
      manipulations can induce infants to detect changes they would not otherwise
      detect. We present an account that includes three systems: a physical-reasoning,
      an object-tracking, and an object-representation system. What impossible changes
      infants detect depends on what object information is included in the physical
      reasoning system; this information becomes subject to a principle of persistence,
      which states that objects can undergo no spontaneous or uncaused change. What
      contextual manipulations induce infants to detect impossible changes depends on
      complex interplays between the physical-reasoning system and the object-tracking
      and object-representation systems.

PMID- 18078780
TI  - Charge transfer complexes of picolines with sigma- and pi-acceptors.
AB  - In the present study CT complexes of 2-, 3- and 4-Picolines with (DDQ) 2, 3
      dichloro-5, 6-dicyano parabenzoquinone (pi-acceptor) and (I2) Iodine (sigma
      acceptor) have been investigated spectrophotometrically in three different
      solvents (CCl4, CHCl3 and CH2Cl2) at six different temperatures. The formation
      constants of the CT complexes were determined by the Benesi-Hildebrand equation.
      The thermodynamic parameters were calculated by Van(')t Hoff equation. The DeltaH
      degrees , DeltaG degrees and DeltaS degrees values are all negative implying that
      the formation of studied complexes is exothermic in nature.

PMID- 18078781
TI  - Laterality of auditory startle responses in humans.
AB  - OBJECTIVE: To examine whether the auditory startle reaction in humans is a
      symmetrical or asymmetrical bilateral brainstem reflex in response to an
      unexpected loud stimulus. METHODS: We investigated physiological side-to-side
      differences of auditory startle responses (ASRs) in 28 healthy adult subjects.
      ASRs were elicited by randomly presented auditory stimuli. Reflex
      electromyographic activity was simultaneously recorded from masseter, orbicularis
      oculi, sternocleidomastoid and biceps brachii muscles bilaterally. RESULTS: ASR
      area-under-the-curve was significantly larger on the side contralateral to hand
      dominance in sternocleidomastoid, and tended to be larger on the dominant side in
      biceps brachii. In contrast, in orbicularis oculi, ASR area was significantly
      larger on the right vs. left side, irrespective of handedness. There was no
      significant side-to-side difference of ASR probability and ASR latency in any
      muscle. CONCLUSIONS: The present data expand our knowledge on physiological
      variables influencing ASRs and provide evidence of laterality of ASRs in
      sternocleidomastoid and biceps brachii, being associated with hand dominance, and
      in orbicularis oculi, irrespective of handedness. SIGNIFICANCE: Normal limits of
      side-to-side differences offer an additional parameter to be taken into account
      in studies of patients presenting with asymmetric symptoms.

PMID- 18078782
TI  - Magnetic sources of the M50 response are localized to frontal cortex.
AB  - OBJECTIVE: To determine the source localization(s) of the midlatency auditory
      magnetic response M50, the equivalent of the P50 potential, a sleep state
      dependent waveform known to habituate to repetitive stimulation. METHODS: We used
      a paired stimulus paradigm at interstimulus intervals of 250, 500 and 1000 ms,
      and magnetoencephalographic (MEG) recordings were subjected to computational
      methods for current density reconstruction, blind source separation, time
      frequency analysis, and data visualization to characterize evoked dynamics.
      RESULTS: Each subject showed localization of a source for primary auditory evoked
      responses in the region of the auditory cortex, usually at a 20-30 ms latency.
      However, responses at 40-70 ms latency that also decreased following the second
      stimulus of a pair were not localizable to the auditory cortex, rather showing
      multiple sources usually including the frontal lobes. CONCLUSIONS: The M50
      response, which shows habituation to repetitive stimulation, was not localized to
      the auditory cortex, but showed multiple sources including frontal lobes.
      SIGNIFICANCE: These MEG results suggest that sources for the M50 response may
      represent non-auditory, perhaps arousal-related, diffuse projections to the
      cortex.

PMID- 18078783
TI  - Differential effects of whole body vibration durations on knee extensor strength.
AB  - The effectiveness and optimality of whole body vibration (WBV) duration on
      muscular strength is yet to be determined. Hence the aim of this study was to
      investigate the effects of three different durations of continuous WBV exposure
      on isometric right knee extensor strength measured pre and post exposure. The
      study involved 12 trained male subjects (age 23.7+/-4.2 years, height 1.82+/
      0.06m, weight 81.8+/-15.5kg). Pre and post knee extensor strength was measured
      using the Biodex System 3. Peak and mean torques were recorded over three maximal
      2s contractions with 10s intervals. All subjects completed three interventions of
      WBV lasting 2, 4, or 6min, in a balanced randomized order. Whole body vibration
      was performed on the Galileo machine set at 26Hz with peak-to-peak amplitude of
      4mm. We found significant interaction (durationxpre-post) effects for both peak
      and mean torque. Two minutes of WBV provided a significantly different (p<0.05)
      effect (peak torque +3.8%, mean torque +3.6%) compared to 4min (-2.7% and -0.8%,
      respectively), and compared to 6min (-6.0% and -5.2%, respectively), while 4min
      produced significantly different results compared to 6min for peak torque
      measurements only. Two minutes of WBV produced an improvement in isometric right
      knee extension strength compared to 4 and 6min, both of which produced strength
      decreases. Nevertheless, the mechanisms and optimal dose-response character of
      vibration exposure remain unclear.

PMID- 18078784
TI  - The reliability of the 1RM strength test for untrained middle-aged individuals.
AB  - The one-repetition maximum (1RM) test is considered the gold standard for
      assessing muscle strength in non-laboratory situations. Since most previous 1RM
      reliability studies have been conducted with experienced young participants, it
      is unclear if acceptable test-retest reliability exists for untrained middle-aged
      individuals. This study examined the reliability of the 1RM strength test of
      untrained middle-aged individuals. Fifty-three untrained males (n=25) and females
      (n=28) aged 51.2+/-0.9 years participated in the study. Participants undertook
      the first 1RM test (T1) 4-8 days after a familiarisation session with the same
      exercises. 1RM was assessed for seven different exercises. Four to eight days
      after T1, participants underwent another identical 1RM test (T2). Ten weeks
      later, 27 participants underwent a third test (T3). Intraclass correlation
      coefficients (ICC), typical error as a coefficient of variation (TEcv), retest
      correlation, repeated measures ANOVA, Bland-Altman plots, and estimation of 95%
      confidence limits were used to assess reliability. A high ICC (ICC>0.99) and high
      correlation (r>0.9) were found for all exercises. TEcv ranged from 2.2 to 10.1%.
      No significant change was found for six of the seven exercises between T1 and T2.
      Leg press was slightly higher at T2 compared to T1 (1.6+/-0.6%, p=0.02). No
      significant change was found between T2 and T3 for any exercise. 1RM is a
      reliable method of evaluating the maximal strength in untrained middle-aged
      individuals. It appears that 1RM-testing protocols that include one
      familiarisation session and one testing session are sufficient for assessing
      maximal strength in this population.

PMID- 18078785
TI  - Heat stress--a challenge for sports science in Australia.

PMID- 18078786
TI  - Is a fatigue index a worthwhile measure of repeated sprint ability?
AB  - The purpose of this opinion piece is to consider the usefulness of fatigue
      measures when describing performance in repeated sprint tests. The reliability of
      different methods of calculating fatigue is discussed and an explanation for the
      large variability explained. Essentially the mathematical procedures involved in
      calculating fatigue levels from a small drop-off in performance will always
      result in an unreliable measure. Consequently, the use of a fatigue index or
      percentage decrement score to describe repeated sprint ability may be questioned.

PMID- 18078787
TI  - Effects of wearing compression garments on thermoregulation during simulated team
      sport activity in temperate environmental conditions.
AB  - Anecdotal evidence suggests compression garments (CGs) are being worn underneath
      normal playing attire during team sports. Wearing CGs as a baselayer could
      possibly increase heat storage, and so this field study investigated the effects
      of wearing CGs, comprising knee-length shorts and short-sleeved top underneath
      normal match-day attire (COMP), versus normal match-day attire alone (NORM) on
      thermoregulation during simulated team sport activity. Ten match-fit field hockey
      players twice performed 4x15min exercise bouts consisting of repeated cycles of
      intermittent, varied-intensity 20m shuttle running (Loughborough intermittent
      shuttle test), once in COMP and once in NORM. Testing was conducted in an indoor
      gymnasium (ambient conditions: approximately 17 degrees C, approximately 60%
      relative humidity). Participants acted as their own controls. Heart rate (HR),
      15m sprint time, ratings of perceived exertion (RPE), blood lactate
      concentration, sweat rate and body core temperature (T(core)) were similar
      between trials (p>0.05). Mean skin temperature (T(skin)) was significantly higher
      in COMP than NORM (p<0.05). Overall, CGs worn as a baselayer during simulated
      team sport exercise in temperate ambient conditions had no thermoregulatory
      benefits nor any detrimental effects on T(core), physiological performance or
      dehydration. However, the higher T(skin) may affect individual preference for
      wearing CGs as an undergarment during team sports.

PMID- 18078788
TI  - Does the diurnal increase in central temperature interact with pre-cooling or
      passive warm-up of the leg?
AB  - Seven male subjects volunteered to participate in an investigation of whether the
      diurnal increase in core temperature influences the effects of pre-cooling or
      passive warm-up on muscular power. Morning (07:00-09:00h) and afternoon (17:00
      19:00h) evaluation of maximal power output during a cycling sprint was performed
      on different days in a control condition (room at 21.8 degrees C, 69% rh), after
      30min of pre-cooling in a cold bath (16 degrees C), or after 30min of passive
      warm-up in a hot bath (38 degrees C). Despite an equivalent increase from morning
      to afternoon in core temperature in all conditions (+0.4 degrees C, P<0.05),
      power output displayed a diurnal increase in control condition only. A local
      cooling or heating of the leg in a neutral environment blunted the diurnal
      variation in muscular power. Because pre-cooling decreases muscle power, force
      and velocity irrespective of time-of-day, athletes should strictly avoid any
      cooling before a sprint exercise. In summary, diurnal variation in muscle power
      output seems to be more influenced by muscle rather than core temperature.

PMID- 18078789
TI  - Effects of wearing compression garments on physiological and performance measures
      in a simulated game-specific circuit for netball.
AB  - This study combined compression garments and Global Positioning System (GPS)
      tracking to examine the effects on key physiological and performance measures in
      a simulated game-specific circuit for netball. Compression garments have
      anecdotal and research supported evidence of enhancing exercise performance.
      However, the absence of sport specificity warrants further investigation. A cross
      over repeated measures design was used to investigate the effectiveness of
      compression garments in improving physiological variables in a netball-specific
      circuit. Field-based measures included 20m sprints, countermovement jumps and
      blood lactate concentrations. Circuit data also used data recorded from GPS
      (GPSpi 10) motion trackers, including heart rates, distance covered, and
      velocity. On separate occasions, three repeats of a netball-specific circuit
      occurred under three different garment conditions (usual netball attire,
      compression garment and placebo garment). Repeated measures ANOVA found no
      garment by dependent variable interactions during the repeated circuits under
      three garment conditions. Analysis of effect sizes however, showed greater
      distances traveled at a faster velocity (3.5ms(-1)) using compression garments in
      comparison to control and placebo garments (Cohen's d=0.86). Using traditional
      statistical analysis, performance enhancing effects of compression garments were
      minimal. However, results of effect sizes analyses showed repeated performances
      at high speeds were improved in this sample of well-trained netball players.

PMID- 18078792
TI  - Rapid identification of mitochondrial DNA (mtDNA) mutations in neuromuscular
      disorders by using surveyor strategy.
AB  - Mutations of mitochondrial genome are responsible for respiratory chain defects
      in numerous patients. We have used a strategy, based on the use of a mismatch
      specific DNA endonuclease named " Surveyor Nuclease", for screening the entire
      mtDNA in a group of 50 patients with neuromuscular features, suggesting a
      respiratory chain dysfunction. We identified mtDNA mutations in 20% of patients
      (10/50). Among the identified mutations, four are not found in any mitochondrial
      database and have not been reported previously. We also confirm that mtDNA
      polymorphisms are frequently found in a heteroplasmic state (15 different
      polymorphisms were identified among which five were novel).

PMID- 18078790
TI  - The use of neuroimaging to study behavior in patients with epilepsy.
AB  - Structural and functional neuroimaging continues to play an increasing role in
      the presurgical evaluation of patients with epilepsy. In addition to its value in
      localizing the epileptogenic zone and eloquent cortex, neuroimaging is
      contributing to our understanding of mood comorbidity in epilepsy. Although the
      vast majority of research has focused on patients with temporal lobe epilepsy
      (TLE), neuroimaging studies of patients with extratemporal epilepsy and primary
      generalized epilepsy are increasing in number. In this review, structural and
      functional imaging modalities that have received considerable research attention
      in recent years are reviewed, and their strengths and limitations for
      understanding behavior in epilepsy are assessed. In addition, advances in
      multimodal imaging are discussed along with their potential application to the
      presurgical evaluation of patients with seizure disorders.

PMID- 18078791
TI  - Expression of unconventional myosin genes during neuronal development in
      zebrafish.
AB  - Neuronal migration and growth cone motility are essential aspects of the
      development and maturation of the nervous system. These cellular events result
      from dynamic changes in the organization and function of the cytoskeleton, in
      part due to the activity of cytoskeletal motor proteins such as myosins. Although
      specific myosins such as Myo2 (conventional or muscle myosin), Myo1, and Myo5
      have been well characterized for roles in cell motility, the roles of the
      majority of unconventional (other than Myo2) myosins in cell motility events have
      not been investigated. To address this issue, we have undertaken an analysis of
      unconventional myosins in zebrafish, a premier model for studying cellular and
      growth cone motility in the vertebrate nervous system. We describe the
      characterization and expression patterns of several members of the unconventional
      myosin gene family. Based on available genomic sequence data, we identified 18
      unconventional myosin- and 4 Myo2-related genes in the zebrafish genome in
      addition to previously characterized myosin (1, 2, 3, 5, 6, 7) genes.
      Phylogenetic analyses indicate that these genes can be grouped into existing
      classifications for unconventional myosins from mouse and man. In situ
      hybridization analyses using EST probes for 18 of the 22 identified genes
      indicate that 11/18 genes are expressed in a restricted fashion in the zebrafish
      embryo. Specific myosins are expressed in particular neuronal or neuroepithelial
      cell types in the developing zebrafish nervous system, spanning the periods of
      neuronal differentiation and migration, and of growth cone guidance and motility.

PMID- 18078794
TI  - Separation of mesenchymal stem cells with magnetic nanosorbents carrying CD105
      and CD73 antibodies in flow-through and batch systems.
AB  - The aim of this study is to develop magnetically loaded nanosorbents carrying
      specific monoclonal antibodies (namely CD105 and CD73) for separation of
      mesenchymal stem cells from cell suspensions. Super-paramagnetic magnetite
      (Fe3O4) nanoparticles were produced and then coated with a polymer layer
      containing carboxylic acid functional groups (average diameter: 153 nm and
      polydispersity index: 0.229). In order to obtain the nanosorbents, the monoclonal
      antibodies were immobilized via these functional groups with quite high coupling
      efficiencies up to 80%. These nanosorbents and also a commercially available one
      (i.e., microbeads carrying CD105 antibodies from Miltenyi Biotec., Germany) were
      used for separation of CD105+ and CD73+ mesenchymal stem cells from model cell
      suspension composed of peripheral blood (97.6%), human bone marrow cells (1.2%)
      and fibroblastic cells (1.2%). The initial concentrations of the CD105+ and CD73+
      cells in this suspension were measured as 5.86% and 6.56%, respectively. A flow
      through separation system and a very simple homemade batch separator unit were
      used. We were able to increase the concentration of CD105+ cells up to about 86%
      in the flow-through separation system with the nanosorbents produced in this
      study, which was even significantly better than the commercial one. The
      separation efficiencies were also very high, especially for the CD73+ cells
      (reached to about 64%) with the very simple and inexpensive homemade batch unit.

PMID- 18078793
TI  - Development and application of a method for analysis of lufenuron in wheat flour
      by gas chromatography-mass spectrometry and confirmation of bio-efficacy against
      Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae).
AB  - A new analytical method using gas chromatography with mass spectrometry (GC-MS)
      for the quantitative determination of lufenuron, a benzoylphenylurea (BPU) class
      of insecticide, from wheat flour has been developed and applied for time
      dependent residue monitoring in treated wheat flour. The analyte was extracted
      from wheat flour by a single step solid-liquid extraction by using ethyl acetate
      and subsequently cleaned up using the Primary Secondary Amine as a sorbent prior
      to GC-MS analysis. The present method provides sufficient sensitivity as
      reflected by the values of limit of detection (LOD) and limit of quantification
      (LOQ), 5 ng/mL (S/N approximately 3) and 50 ng/mL (the lowest validation point on
      the calibration curve), respectively. The calibration curve showed an excellent
      linearity in the concentration range of 50-1000 ng/mL (r2=0.998). The average
      recovery for spiked samples at three concentrations (150, 300, and 450 ng/g) was
      98.23+/-2.52% R.S.D. The method was applied for the determination of lufenuron
      residues in treated wheat flour samples. Simultaneous determination of bio
      efficacy of lufenuron residues was also carried out against the red flour beetle,
      Tribolium castaneum to correlate the actual residual effect of lufenuron as
      detected by the analytical method, over a period of 3 months. The findings
      revealed that the residual concentration of lufenuron were neither uniform nor in
      descending order over a period of 3 months in wheat flour, possibly because of an
      uneven dispersal in the treated wheat which was subsequently milled into flour,
      as confirmed by GC-MS analysis. However, the residues of lufenuron were
      sufficient to produce 100% mortality of T. castaneum larvae up to 3 months. The
      results have been discussed in view of the potential of lufenuron as a candidate
      molecule for the control of stored product pests.

PMID- 18078795
TI  - Malignant melanoma on congenital naevus: a case of degeneration in a 6-month-old
      child with severe histological criteria.
AB  - Malignant melanoma in children is a rare and poorly understood pathology. We
      report a case of nodular melanoma that developed on congenital naevus in a 6
      month-old infant. The histological results revealed a nodular melanoma on a
      congenital naevus measuring 6.625 mm in tumour thickness according to Breslow.
      The infant was treated by broad resection without adjuvant treatment. Follow up
      is 43 months without metastasis. Malignant melanoma is a rare pathology: 1-4% of
      all melanomas occur before the age of 20 and 0.3-0.4% of those are before
      puberty. The risk of degeneration of a congenital naevus into a melanoma is
      approximately 0.7%. Surgical exeresis must be broad. Up to now, no complementary
      treatment has proven to be effective. Pre-operative examination for sentinel
      lymph nodes by lymphography can be of interest although such an examination is
      difficult in children. The prognosis would appear to be similar to that of
      malignant melanoma in adults with a high mortality. This is therefore an argument
      in favour of early treatment and prolonged follow up of children with malignant
      melanoma.

PMID- 18078796
TI  - The use of artificial dermis (Integra) and topical negative pressure to achieve
      limb salvage following soft-tissue loss caused by meningococcal septicaemia.
AB  - Meningococcal sepsis leading to purpura fulminans leaves survivors with extensive
      areas of skin and soft-tissue necrosis. Soft-tissue loss in the limbs may result
      in large areas of exposed bone, leaving a choice between free tissue transfer and
      amputation. We present a case of meningococcal sepsis where the entire medial and
      lateral surfaces of the tibiae were exposed with loss of anterior muscle
      compartments on each side. Faced with the possibility of bilateral above-knee
      amputation, these were instead covered using the dermal replacement Integra
      (Integra LifeSciences Corp.), in conjunction with an antimicrobial dressing,
      topical negative pressure dressing and subsequent skin grafting. This management
      decision achieved rapid wound closure avoiding amputation. Additional secondary
      reconstruction with microvascular free flaps was performed to preserve joint
      function.

PMID- 18078797
TI  - Activation of polyvinyl chloride sheet surface for covalent immobilization of
      oxalate oxidase and its evaluation as inert support in urinary oxalate
      determination.
AB  - Polyvinyl chloride (PVC) sheets are a promising material for enzyme
      immobilization owing to the PVC's properties such as being chemically inert,
      corrosion free, weather resistant, tough, lightweight, and maintenance free and
      having a high strength-to-weight ratio. In this study, this attractive material
      surface was chemically modified and exploited for covalent immobilization of
      oxalate oxidase using glutaraldehyde as a coupling agent. The enzyme was
      immobilized on activated PVC surface with a conjugation yield of 360
      microg/cm(2). The scanning electron micrographs showed the microstructures on the
      PVC sheet surface revealing the successful immobilization of oxalate oxidase. A
      colorimetric method was adopted in evaluating enzymatic activity of immobilized
      and native oxalate oxidase. The immobilized enzyme retained 65% of specific
      activity of free enzyme. Slight changes were observed in the optimal pH,
      incubation temperature, and time for maximum activity of immobilized oxalate
      oxidase. PVC support showed no interference when immobilized oxalate oxidase was
      used for estimation of oxalic acid concentration in urine samples and showed a
      correlation of 0.998 with the values estimated with a commercially available
      Sigma kit. The overall results strengthen our view that PVC sheet can be used as
      a solid support for immobilization of enzymes and in the field of clinical
      diagnostics, environmental monitoring and remediation.

PMID- 18078798
TI  - Taking aim at shotgun phosphoproteomics.

PMID- 18078799
TI  - A method for analyzing lipid-modified proteins with mass spectrometry.
AB  - In protein analysis using mass spectrometry, proteins are usually separated by
      electrophoresis and digested within the gel with proteases such as trypsin.
      However, analysis of lipid-modified proteins is difficult due to the low recovery
      of lipid-modified peptide fragments from the gel as well as their low ionization
      efficiency during mass spectrometry. In this study, we developed a simple
      extraction method with n-dodecyl-beta-D-maltoside following chloroform/methanol
      extraction that efficiently elutes lipid-modified fragments from gels. This
      method allowed us to analyze the structure of lipid-modified fragments,
      suggesting the applicability of the method for analysis of lipid-modified
      fragments by mass spectrometry.

PMID- 18078800
TI  - Spectrophotometric assay for protease activity in ionic liquids using chromogenic
      substrates.
AB  - A new spectrophotometric assay has been developed to evaluate protease activity
      in ionic liquids (ILs). The assay consists of two strategies to enable real-time
      spectrometric analysis of enzymatic reaction in ILs. First, enzymes are modified
      with a comb-shaped poly(ethylene glycol), PM(13), to obtain a transparent enzyme
      solution in IL. Second, a chromogenic substrate is used to follow the enzymatic
      reaction in IL. p-Nitroaniline-derivatized substrates are subjected to protease
      catalyzed alcoholysis to release chromogenic p-nitroaniline that can be
      quantitatively detected by a UV-Vis spectrophotometer. By using this method, we
      can evaluate protease activity in ILs quite easily without separation of products
      from the reaction mixture. The availability of the novel assay system was
      demonstrated in a kinetic analysis of subtilisin-catalyzed reaction in the IL 1
      ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Emim][Tf(2)N])
      under different reaction conditions. Because two different serine proteases,
      subtilisin and alpha-chymotrypsin, substantially retained its original substrate
      specificity in the IL, the assay can be extended to other enzymes by using
      suitable chromogenic substrates.

PMID- 18078801
TI  - Quantitative real-time PCR assay to detect transgene copy number in cotton
      (Gossypium hirsutum).
AB  - A TaqMan quantitative real-time PCR detection system was developed to examine
      transgene copy number in cotton. GhUBC1, a gene validated to be present as a
      single copy per haploid Gossypium hirsutum genome, was used as the endogenous
      reference to estimate copy number of GFP and selection marker NPTII in 28 T0
      plants. This system was found to be more accurate than genomic Southern blot
      hybridization and could effectively tell homozygotes from heterozygotes in a T1
      transgenic cotton population. Therefore it is suitable for efficient and cost
      effective early screening of transgenic seedlings and identifying transgene
      homozygotes in segregation populations.

PMID- 18078803
TI  - Characterization of antibody-antigen interactions: comparison between surface
      plasmon resonance measurements and high-mass matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - The interaction between the bovine prion protein (bPrP) and a monoclonal
      antibody, 1E5, was studied with high-mass matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry (MS) and surface plasmon
      resonance (SPR). In the case of MS a cross-linking stabilization was used prior
      to the analysis, whereas for SPR the antibody was immobilized and bPrP was
      injected. We compared the determination of parameters such as the epitope, the
      kinetics and binding strength, and the capacity of the antigen to bind two
      different antibodies. The two methods are highly complementary. SPR measurements
      require a lower amount of sample but are more time-consuming due to all of the
      necessary side steps (e.g., immobilization, regeneration). High-mass MALDI MS
      needs a higher overall amount of sample and cannot give direct access to the
      kinetic constants, but the analysis is faster and easier compared with SPR.

PMID- 18078802
TI  - Separation of biomacromolecules by electrofiltration through gel layers.
AB  - A straightforward method for concomitant separation and isolation of
      biomacromolecules from a mixture in solution was developed. Three gel layers that
      comprise a middle separation layer of 10% polyacrylamide gel were constructed.
      This gel system was formed in an electroconcentration apparatus above a
      collection chamber surrounded at the bottom by a dialysis membrane. The mixture
      is applied over the gel layers where biomacromolecules are caused to migrate by
      electrophoresis through the gel system, where they are separated into discrete
      bands and electroeluted into the collection chamber without dismantling the
      apparatus. The isolated biomacromolecules are removed from the chamber in a
      highly pure and concentrated form ready for further investigations. Cooling can
      be applied throughout the whole process, and the setup and conditions of run can
      be modified according to the characteristics of the biomacromolecules to be
      purified. The components of a mixture containing the glycoprotein ovalbumin and
      bovine serum albumin monomer, dimer, and tetramer were successfully isolated as
      concentrated and highly pure fractions with good recoveries ranging from 70 to
      89%. Other proteins were successfully isolated under denaturing conditions in the
      presence of sodium dodecyl sulfate (SDS) or 6 M urea.

PMID- 18078804
TI  - Spectroscopic study on the communication between a heme a3 propionate, Asp399 and
      the binuclear center of cytochrome c oxidase from Paracoccus denitrificans.
AB  - The proton pumping mechanism of cytochrome c oxidase on a molecular level is
      highly disputed. Recently theoretical calculations and real time electron
      transfer measurements indicated the involvement of residues in the vicinity of
      the ring A propionate of heme a3, including Asp399 and the CuB ligands His 325,
      326. In this study we probed the interaction of Asp399 with the binuclear center
      and characterize the protonation state of its side chain. Redox induced FTIR
      difference spectra of mutations at the site in direct comparison to wild type,
      indicate that below pH 5 Asp 399 displays signals typical for the deprotonation
      of the acidic residue with reduction of the enzyme. Interestingly at a pH higher
      than 5, no contributions from Asp 399 are evident. In order to probe the
      interaction of the site with the binuclear center we followed the rebinding of CO
      by infrared spectroscopy for mutations on residue Asp399 to Glu, Asn and Leu.
      Previously different CO conformers have been identified for bacterial cytochrome
      c oxidases, and its pH dependent behaviour discussed to be relevant for
      catalysis. Interestingly we observe the lack of this pH dependency and a strong
      influence on the observable conformers for all mutants studied here, clearly
      suggesting a communication of the site with the heme-copper center and the nearby
      histidine residues.

PMID- 18078806
TI  - AP-1 and retromer play opposite roles in the trafficking of sortilin between the
      Golgi apparatus and the lysosomes.
AB  - Sortilin has been implicated in the sorting of one soluble hydrolase and two
      sphingolipid activator proteins to the lysosomes. While the GGA adaptor proteins
      have been demonstrated to play a role in the targeting of sortilin to the
      endosomes, the recycling of sortilin has not yet been elucidated. Here we examine
      the role of two adaptor protein complexes, AP-1 and retromer. Our results
      demonstrate that AP-1 is required for the transport of sortilin to the endosomes
      and retromer for the recycling of sortilin to the Golgi apparatus. While
      inhibition of AP-1 causes accumulation of sortilin in the Golgi apparatus, RNAi
      depletion of retromer results in retention of sortilin in the lysosomes. We also
      demonstrate that the interaction of sortilin with retromer occurs through a
      YXXPhi site in its cytosolic tail. In conclusion, our observations indicate that
      retromer and AP-1 play opposite roles in the trafficking of sortilin.

PMID- 18078807
TI  - Base-pairing properties of the oxidized cytosine derivative, 5-hydroxy uracil.
AB  - The most abundant base-substitution mutation resulting from oxidative damage to
      DNA is the GC to AT transition mutation. 5-hydroxyuracil (5-OHU), produced by the
      oxidative deamination of cystosine, has been established as the major chemical
      precursor for this most abundant transition mutation. Results from NMR
      spectroscopy and UV melting experiments show that 5-OHU would form the most
      stable pair with G, and the least stable pair with C. The hydroxyl group in the
      5th position of the 5-OHU residue may play a role in increasing the stability of
      the 5-OHU:G pair over the normal Watson-Crick pair, the 5-OHU:A. The 5-OHU:C base
      pair would be least stable, and would destabilize the base-stacking in the
      duplex. Our results explain why certain DNA polymerases preferentially
      incorporate G opposite to 5-OHU over A and why C does not get incorporated
      against 5-OHU during DNA replication in vivo.

PMID- 18078808
TI  - Potent inhibition of human influenza H5N1 virus by oligonucleotides derived by
      SELEX.
AB  - New therapeutics are urgently needed for the treatment of pandemic influenza
      caused by H5N1 influenza virus mutants. Aptamer was a promising candidate for
      treatment and prophylaxis of influenza virus infections. In this study, systemic
      evolution of ligands through exponential enrichment (SELEX) was used to screen
      DNA aptamers targeted to recombinant HA1 proteins of the H5N1 influenza virus.
      After 11 rounds of selection, DNA aptamers that bind to the HA1 protein were
      isolated and shown to have different binding capacities. Among them, aptamer 10
      had the strongest binding to the HA1 protein, and had an inhibitory effect on
      H5N1 influenza virus, as shown by the hemagglutinin and MTT assays. These results
      should aid the development of new drugs for the prevention and control of
      influenza virus infections.

PMID- 18078805
TI  - Studies on anticancer activities of antimicrobial peptides.
AB  - In spite of great advances in cancer therapy, there is considerable current
      interest in developing anticancer agents with a new mode of action because of the
      development of resistance by cancer cells towards current anticancer drugs. A
      growing number of studies have shown that some of the cationic antimicrobial
      peptides (AMPs), which are toxic to bacteria but not to normal mammalian cells,
      exhibit a broad spectrum of cytotoxic activity against cancer cells. Such studies
      have considerably enhanced the significance of AMPs, both synthetic and from
      natural sources, which have been of importance both for an increased
      understanding of the immune system and for their potential as clinical
      antibiotics. The electrostatic attraction between the negatively charged
      components of bacterial and cancer cells and the positively charged AMPs is
      believed to play a major role in the strong binding and selective disruption of
      bacterial and cancer cell membranes, respectively. However, it is unclear why
      some host defense peptides are able to kill cancer cells when others do not. In
      addition, it is not clear whether the molecular mechanism(s) underlying the
      antibacterial and anticancer activities of AMPs are the same or different. In
      this article, we review various studies on different AMPs that exhibit cytotoxic
      activity against cancer cells. The suitability of cancer cell-targeting AMPs as
      cancer therapeutics is also discussed.

PMID- 18078809
TI  - Alpha(E)-Catenin induces SRF-dependent transcriptional activity through its C
      terminal region and is partly RhoA/ROCK-dependent.
AB  - The ubiquitous alpha(E)-catenin is an essential actin cytoskeletal linker. The
      transcription factor, serum response factor (SRF), induces transcription via
      binding to the serum response element (SRE) in gene promoters, and in many cases
      responds to actin dynamics. Here, we report that alpha(E)-catenin expression in
      HEK293 cells activates the SRE.L transcriptional reporter, a reporter containing
      the isolated SRF-binding site, and a stably integrated SRE.L reporter in
      fibroblasts. alpha-Catenin-induced reporter activity appears only partly
      dependent on RhoA GTPase and Rho kinase function. alpha-Catenin expression has no
      effect on RhoA activation or localization, and alpha-catenin-induced SRE.L
      reporter activation is insensitive to the actin-modulating agent latrunculin B.
      Ectopic alpha-catenin expression was not sufficient to induce actin filament
      assembly as measured by stress fiber formation. SRE.L reporter is activated by
      the C-terminal approximately 300 residue region of alpha(E)-catenin. These
      results suggest induction of SRF-mediated transcription by alpha(E)-catenin
      either downstream of RhoA or via a parallel pathway.

PMID- 18078810
TI  - Repression of Smad3 activity by histone demethylase SMCX/JARID1C.
AB  - SMCX/JARID1C was recently shown to be a histone H3 lysine 4 (H3K4) demethylase.
      Here, we have identified an SMCX isoform that predominantly resides in the
      cytoplasm, but still efficiently demethylates trimethylated H3K4. SMCX requires
      several functional domains for its demethylase activity and is also capable of
      forming homomers through amino acids 204-493. Further, SMCX physically interacts
      with Smad3, a mediator of transforming growth factor-beta (TGF-beta), and
      overexpression of SMCX inhibits the ability of Smad3 to activate transcription.
      Thus, SMCX is a novel Smad3 corepressor that may antagonize the tumor suppressing
      activity of the TGF-beta/Smad3 signaling pathway and thereby contribute to
      tumorigenesis. Indeed, SMCX is overexpressed in prostate tumors and seminomas,
      suggesting that SMCX might be a novel oncogene.

PMID- 18078811
TI  - A novel nucleolar transcriptional activator ApLLP for long-term memory formation
      is intrinsically unstructured but functionally active.
AB  - A novel Aplysia nucleolar protein ApLLP has been recently characterized to be a
      transcriptional activator that binds to the cAMP-response element (CRE) and thus
      induces ApC/EBP expression required for establishing long-term memory. So far, no
      structural information is available for both ApLLP and its homologs. Here, we
      expressed the entire ApLLP and its two dissected fragments, followed by
      structural and binding studies using CD and NMR spectroscopy. The study leads to
      two interesting findings: (1) all three ApLLP proteins are highly disordered,
      owning no predominant secondary and tertiary structures; (2) ApLLP is capable of
      binding the CRE DNA element but this induces no significant change in its
      secondary and tertiary structures. Intriguingly, it appears that the DNA-binding
      residues are mainly located on the C-half of the ApLLP molecule. Taken together,
      our results define ApLLP as an intrinsically unstructured protein and may bear
      important implications in understanding the molecular mechanism underlying ApLLP
      functions.

PMID- 18078812
TI  - Isomerization and/or racemization at Asp23 of Abeta42 do not increase its
      aggregative ability, neurotoxicity, and radical productivity in vitro.
AB  - Aggregation of the 42-mer amyloid beta peptide (Abeta42) plays a pivotal role in
      the pathogenesis of Alzheimer's disease. Recent investigations suggested the
      isomerization and/or racemization of Asp at position 1, 7, or 23 to be associated
      with the pathological role of Abeta42. Our previous study indicated that the turn
      at positions 22 and 23 of Abeta42 is closely related to its neurotoxicity through
      the formation of radicals. To clarify the contribution of these modifications at
      Asp23 to the pathology, three isomerized and/or racemized Abeta42 mutants were
      prepared. l-isoAsp23- and d-Asp23-Abeta42 showed moderate aggregative ability
      similar to the wild type. However, d-Asp23-Abeta42 was less neurotoxic than the
      wild type, while l-isoAsp23-Abeta42 was as toxic as the wild type. In contrast, d
      isoAsp23-Abeta42 showed weak aggregative ability without neurotoxicity. These
      results suggest the isomerization and/or racemization of Asp23 not to be related
      to the pathogenesis, but to be a consequence of chemical reactions during the
      long-term deposition of fibrils.

PMID- 18078813
TI  - Circulating TNFR1 exosome-like vesicles partition with the LDL fraction of human
      plasma.
AB  - Extracellular type I tumor necrosis factor receptors (TNFR1) are generated by two
      mechanisms, proteolytic cleavage of TNFR1 ectodomains and release of full-length
      TNFR1 in the membranes of exosome-like vesicles. Here, we assessed whether TNFR1
      exosome-like vesicles circulate in human blood. Immunoelectron microscopy of
      human serum demonstrated TNFR1 exosome-like vesicles, with a diameter of 27-36nm,
      while Western blots of human plasma showed a 48-kDa TNFR1, consistent with a
      membrane-associated receptor. Gel filtration chromatography revealed that the 48
      kDa TNFR1 in human plasma co-segregated with LDL particles by size, but
      segregated independently by density, demonstrating that they are distinct from
      LDL particles. Furthermore, the 48-kDa exosome-associated TNFR1 in human plasma
      contained a reduced content of N-linked carbohydrates as compared to the 55-kDa
      membrane-associated TNFR1 from human vascular endothelial cells. Thus, a distinct
      population of TNFR1 exosome-like vesicles circulate in human plasma and may
      modulate TNF-mediated inflammation.

PMID- 18078814
TI  - A universal algorithm for de novo decrypting of heterozygous indel sequences: a
      tool for personalized medicine.
AB  - INTRODUCTION: Indels (insertions/deletions) are important DNA sequence variations
      because of the high frequency in the human genome, the deleterious effects on the
      reading frame and protein expression, and the association with disease and
      disease susceptibility of common diseases. In a recent study with a human
      individual with the whole genome sequenced, 292,102 heterozygous indels and
      559,473 homozygous indels were identified. Decrypting such a large number of
      heterozygous indels is computationally intensive and requires efficient
      algorithms. However, the current algorithms for decrypting heterozygous indel
      cannot be applied to unprecedented sequenced genomes and cannot be performed
      without reference sequences or reference sequence tracings for sequenced genomes.
      METHODS: A new algorithm for de novo decrypting of heterozygous indels is
      conceptualized in the direction of isolating the indel sequence from the genotype
      or diploid sequence. A universal algorithm is described, here, for heterozygous
      indel detection, indel size determination, and de novo decrypting of the indel
      sequence without subtracting the diploid DNA sequence from the reference sequence
      or reference sequence tracing. RESULTS: The result obtained by this algorithm is
      exactly the same as that obtained by PolyPhred and PolyScan. Unlike these
      algorithms, this new algorithm is not computationally intense for large indels,
      is independent of sequencing technologies and applies to genotype data derived
      from all existing sequencing technology platforms. A read of only 29 bases is
      enough to reduce the false detection rate (FDR) to 1 in a million. CONCLUSIONS:
      This algorithm is unique amongst all the existing algorithms in terms of
      performing the task of indel detection, size determination, and decrypting
      simultaneously. This universal approach eliminates the requirement of a reference
      sequence or sequence tracing and makes this algorithm unique in decrypting
      unprecedented sequenced genomes. Because of the high frequency of heterozygous
      indels in human genome, this universal algorithm will greatly reduce the time
      required for post-sequencing data analysis in whole genome sequencing of an
      individual for the practice of personalized medicine.

PMID- 18078815
TI  - Roles of the genetic variation of alcohol-metabolizing enzymes on biomarkers in
      trauma patients with excessive alcohol intake at emergency department.
AB  - BACKGROUND: Alcohol abuse has been implicated as an important factor for
      accidents. We evaluated the roles of different genetic combinations of the ADH2
      and ALDH2 genotypes on biomarkers in trauma patients with excessive alcohol
      intake at our emergency department. METHODS: Blood samples were obtained from 80
      patients and 88 age-matched controls. The biomarkers, including AST, ALT, GGT,
      and MDA, were assayed. The polymerase chain reaction-restriction fragment length
      polymorphism method was used to determine the genetic polymorphisms of ADH2 and
      ALDH2. RESULTS: There were significant differences in the levels of AST, ALT,
      GGT, MDA, and AST/ALT ratios between the 2 groups. In addition, MDA values and
      AST/ALT ratios were significantly higher in the patients with normal activity of
      ADH2 than the patients with low activity of ADH2. Meanwhile, regarding ALDH2
      genotypes, there were significantly higher ratios of AST/ALT in the patients with
      low activity of ALDH2. The highest AST/ALT ratios and MDA values were in the
      patients with ADH2 (*2/*2) and ALDH2 (*1/*2 and *2/*2). CONCLUSIONS: In
      conclusion, our results indicated that alcohol-induced liver damage or oxidative
      stress might be influenced by the genetic variation of ADH2 or ALDH2. Therefore,
      the combinations of different ADH2 and ALDH2 genotypes may be influential markers
      for susceptibility to alcohol-induced liver damage.

PMID- 18078816
TI  - Determination of serum zinc-alpha-2-glycoprotein in patients with metabolic
      syndrome by a new ELISA.
AB  - OBJECTIVES: To develop an assay for the determination of ZAG in human serum, and
      to investigate its clinical relevance as a marker of metabolic syndrome. DESIGN
      AND METHODS: A new sandwich ELISA was introduced and clinically tested. RESULTS:
      ZAG serum level did not differentiate healthy subjects (27.4+/-8.3 mg/L; N=132)
      from patients with metabolic syndrome (24.9+/-8.1; N=92). ZAG correlated with
      glucose, creatinine and uric acid. CONCLUSION: The immunoassay offers a new
      research tool for glucose metabolism.

PMID- 18078817
TI  - Multiple genetic determinants of plasma lipid levels in Caribbean Hispanics.
AB  - OBJECTIVES: To identify candidate genes in relation to plasma lipid levels in
      Caribbean Hispanics. DESIGN AND METHODS: A total of 114 single nucleotide
      polymorphisms (SNPs) at 17 lipid-related genes were genotyped in 477 Caribbean
      Hispanics from the Northern Manhattan Study (NOMAS). Analyses for each SNP and
      haplotype were performed to evaluate the associations with four lipid traits:
      high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), triglyceride (TG)
      and total cholesterol (TC). RESULTS: We identified 19 SNPs at 10 genes that were
      significantly related to lipids (p<0.01), including nine involved in the reverse
      cholesterol transport pathway, and one involved in bile acid synthesis. Three
      genes, namely the apolipoprotein A5, apolipoprotein B and cytochrome p450
      polypeptide 7A1 genes, accounted for the largest proportion of variation in HDL
      C/TG, TC and LDL-C respectively. CONCLUSIONS: The cumulative effects of multiple
      genetic variants led to a substantially better prediction of inter-individual
      variations in lipid levels.

PMID- 18078819
TI  - Similar toxicity of the oligomeric molten globule state and the prefibrillar
      oligomers.
AB  - We report that a mutant of human stefin B is in a molten globule conformation. It
      has all the spectroscopic characteristics for such a state. We also demonstrate
      that the molten globule is oligomeric, eluting on SEC within a similar MW range
      than the higher order oligomers of the wild type protein, which is confirmed by
      DLS and AFM. Both, the higher oligomers and the molten globule state bind ANS,
      implying a high degree of hydrophobic patches exposure and partial opening of the
      structure. Finally, we demonstrate that the oligomeric molten globule is as toxic
      as the prefibrillar aggregates obtained at acid pH or the higher order oligomers
      prepared at neutral pH.

PMID- 18078818
TI  - Induction of trophinin in human endometrial surface epithelia by CGbeta and IL
      1beta.
AB  - During embryo implantation, trophinin mediates cell adhesion by homophilic
      binding at the apical surfaces of trophectoderm and endometrium. Trophinin is
      expressed on the human endometrial epithelia in rare occasions. We developed hCG
      coated agarose beads that mimic the physical and physiological features of an
      implantation-stage human blastocyst. When hCG-coated beads were applied to human
      endometrial epithelial cells in the presence of IL-1beta, endometrial cells
      acquired strong trophinin expression and the ability for apical cell adhesion
      with trophinin-expressing human trophoblastic cells. These results provide a
      mechanism for trophinin-mediated adhesion of human blastocyst to endometrium by a
      spatially and temporally restricted paracrine effect of hCG derived from the
      blastocyst.

PMID- 18078820
TI  - Ezrin is a specific and direct target of protein tyrosine phosphatase PRL-3.
AB  - Phosphatase of Regenerating Liver-3 (PRL-3) is a small protein tyrosine
      phosphatase considered an appealing therapeutic cancer target due to its
      involvement in metastatic progression. However, despite its importance, the
      direct molecular targets of PRL-3 action are not yet known. Here we report the
      identification of Ezrin as a specific and direct cellular substrate of PRL-3. In
      HCT116 colon cancer cell line, Ezrin was identified among the cellular proteins
      whose phosphorylation level decreased upon ectopic over-expression of wtPRL-3 but
      not of catalytically inactive PRL-3 mutants. Although PRL-3 over-expression in
      HCT116 cells appeared to affect Ezrin phosphorylation status at both tyrosine
      residues and Thr567, suppression of the endogenous protein by RNA interference
      pointed to Ezrin-Thr567 as the residue primarily affected by PRL-3 action. In
      vitro dephosphorylation assays suggested Ezrin-Thr567 as a direct substrate of
      PRL-3 also proving this enzyme as belonging to the dual specificity phosphatase
      family. Furthermore, the same effect on levels of pThr567, but not on pTyr
      residues, was observed in endothelial cells pointing to Ezrin-pThr567
      dephosphorylation as a mean through which PRL-3 exerts its function in promoting
      tumor progression as well as in the establishment of the new vasculature needed
      for tumor survival and expansion.

PMID- 18078821
TI  - Role of glycosphingolipid-enriched microdomains in innate immunity: microdomain
      dependent phagocytic cell functions.
AB  - The innate immune system is the first line of defense against pathogenic
      microorganisms, such as bacteria, fungi, and viruses. Phagocytes, such as
      neutrophils and macrophages, play an important role in the innate immune system
      by recognizing, engulfing, and eliminating pathogens. It has been suggested that
      lipid membrane microdomains/rafts of phagocytes are involved in these innate
      immune responses, including superoxide generation, cell migration, and
      phagocytosis. Lactosylceramide (LacCer), a neutral glycosphingolipid, forms
      glycosphingolipid-enriched microdomains together with the Src family kinase, Lyn,
      on the neutrophil plasma membrane. LacCer-enriched microdomains have been
      suggested to play important roles in innate immune function of neutrophils.
      However, the molecular mechanisms underlying these phenomena remain largely
      unknown. Recent proteomic analyses of microdomains from phagocytes have provided
      insight into membrane microdomain-mediated functions in the processes of
      phagocytosis. In this review, we discuss the membrane microdomain-associated
      immune functions of phagocytes, focusing on those functions of LacCer-enriched
      microdomains and recent proteomic approaches to determine the molecular
      mechanisms underlying these functions.

PMID- 18078822
TI  - U7 snRNA acts as a transcriptional regulator interacting with an inverted CCAAT
      sequence-binding transcription factor NF-Y.
AB  - An inverted CCAAT sequence is recognized by both transcription factors NF-Y and
      DNA/RNA binding protein YB-1. In the process of examining the effect of nuclear
      RNA on an inverted CCAAT-containing promoter of MDR1 gene, we found that U7 snRNA
      inhibits NF-Y and suppresses the promoter activity both in vitro and in NG108-15
      tumor cells. Analysis using a designed RNA, which was structurally unrelated to
      U7 snRNA, revealed that RNA binding by YB-1 is not specific and that the protein
      is not involved in the transcription. Furthermore, we demonstrated that in the
      nucleus of doxorubicin-treated cells, DNA binding by NF-Y and transcriptional
      activity of the promoter were inhibited without either a decrease of NF-Y or an
      increase of the p53 tumor suppressor, which is known to inhibit DNA binding by NF
      Y. In these cells, U7 snRNA was specifically increased and associated with NF-Y,
      and treatment with RNase A eliminated the inhibition of NF-Y activity. These
      results suggest that U7 snRNA has a novel function as a transcriptional regulator
      to control NF-Y.

PMID- 18078823
TI  - Focal adhesion kinase as well as p130Cas and paxillin is crucially involved in
      the enhanced malignant properties under expression of ganglioside GD3 in melanoma
      cells.
AB  - Mass spectrometry analysis of immunoprecipitates from serum-treated GD3
      expressing melanoma cells with PY20 (anti-phosphotyrosine antibody) revealed that
      focal adhesion kinase (FAK) is more strongly activated in GD3-expressing cells
      than in GD3-negative cells. Involvement of FAK in the increased proliferation and
      invasion in GD3-expressing melanomas was demonstrated by siRNA-mediated
      knockdown. Also, it was shown that FAK is located up-stream of p130Cas and
      paxillin in the enhanced signaling pathway. GD3 expression enhanced the
      association of FAK with p130Cas after treatment with fetal calf serum. Thus,
      focal adhesion kinase as well as p130Cas and paxillin should be a crucial
      molecule undergoing stronger tyrosine phosphorylation in GD3-expressing melanoma
      cells. Molecules linking GD3 and FAK such as integrins in the enhanced signaling
      pathway remain to be investigated.

PMID- 18078824
TI  - Role of intracellular cAMP in differentiation-coupled induction of resistance
      against oxidative damage in Leishmania donovani.
AB  - Even though the human parasite Leishmania donovani encounters tremendous
      oxidative burst during macrophage invasion, a set of parasites survives and
      proliferates intracellularly, leading to transformation from promastigote to
      amastigote form and disease manifestation. The striking shifts in temperature
      (from 22 degrees C in the insect gut to 37 degrees C in the mammalian host) and
      pH (7.2 in the insect gut to 5.5 in the parasitophorous vacuole of macrophages)
      are the key environmental triggers for differentiation as these cause an arrest
      in the G1 stage of the cell cycle and initiate transformation. Using an
      established in vitro culture and differentiation system our study demonstrates
      that the differentiation-triggering environment induces resistance to oxidative
      damage and consequently enhances infectivity. Differentiation conditions caused a
      three- to fourfold elevation in cAMP level as well as cAMP-dependent protein
      kinase activity. Similar to stress exposure, positive modulation of intracellular
      cAMP resulted in blockage of cell cycle progression and induction of resistance
      against oxidative damage. Resistance against pro-oxidants from either stress or
      cAMP may be associated with upregulation of the expression of three major
      antioxidant genes, peroxidoxin 1, trypanothione reductase, and superoxide
      dismutase A. Positive modulation of the intracellular cAMP response enables cells
      to resist the cytotoxic effects of pro-oxidants. In contrast, downregulation of
      intracellular cAMP by overexpression of cAMP phosphodiesterase A resulted in a
      decrease in resistance against oxidative damage and reduced infectivity toward
      activated macrophages. This study for the first time reveals the importance of
      cAMP response in the life cycle and infectivity of the Leishmania parasite.

PMID- 18078825
TI  - Sustained hypoxia modulates mitochondrial DNA content in the neonatal rat brain.
AB  - The effects of placental insufficiency and preterm birth on neurodevelopment can
      be modeled in experimental settings of neonatal hypoxia in rodents. Here, rat
      pups were reared in reduced oxygen (9.5%) for 11 days, starting on postnatal day
      3 (P3). This led to a significant reduction in brain and body weight gain in
      hypoxic pups compared to age-matched normoxia-reared controls, plausibly
      reflecting an inability to fulfill the energetic needs of normal growth and
      development. Adaptive processes designed to augment energetic capacity in
      eukaryotes include stimulation of mitochondrial biogenesis. We show that after 11
      days of sustained hypoxia, the levels of nuclear respiratory factor-1 and
      mitochondrial transcription factor A are elevated and the content of
      mitochondrial DNA (mtDNA) is greater in the hypoxic P14 pup brain compared to
      normoxic conditions. Corresponding immunohistochemical analyses reveal increased
      density of mtDNA in large cortical neurons. In contrast, no changes in mtDNA
      content are observed in the brain of pups reared for 24 h (P3-P4) under hypoxic
      conditions. Together, these data suggest that prolonged inadequate oxygenation
      may trigger a compensatory increase in neuronal mitochondrial DNA content to
      partially mitigate compromised energy homeostasis and reduced energetic capacity
      in the developing hypoxic brain.

PMID- 18078826
TI  - The role of redox-sensitive transcription factors NF-kappaB and AP-1 in the
      modulation of the Cyp1a1 gene by mercury, lead, and copper.
AB  - We have previously shown that Hg(2+), Pb(2+), and Cu(2+) significantly induced
      the expression of Cyp1a1 mRNA, but the catalytic activity was inhibited by the
      three metals, and the inhibition was accompanied by an increase in the oxidative
      stress status. In the current study we investigated the role of redox-sensitive
      transcription factors and the NF-kappaB and AP-1 signaling pathways in the metal
      mediated effects on Cyp1a1 gene expression. We show that heavy metals caused the
      induction of oxidative stress markers, such as reactive oxygen species and heme
      oxygenase-1, and the depletion of cellular glutathione content, which was
      associated with NF-kappaB and AP-1 activation. In addition, the NF-kappaB
      activator PMA significantly abolished the metal-mediated induction of Cyp1a1
      mRNA, whereas it further potentiated their inhibitory effects on Cyp1a1 activity.
      In parallel, the NF-kappaB inhibitor PDTC further potentiated the metal-mediated
      induction of Cyp1a1 mRNA, whereas it reversed their inhibitory effects on Cyp1a1
      activity. Inhibition of AP-1 upstream signaling pathway activators such as JNK by
      SP600125 suppressed Cyp1a1 mRNA induction by heavy metals, whereas it potentiated
      their inhibitory effects at the activity level. In contrast, the ERK inhibitor
      U0126 further potentiated heavy metal-mediated induction of Cyp1a1 mRNA, whereas
      it reversed their inhibitory effects on the Cyp1a1 activity. The p38 MAPK
      inhibitor SB203580 suppressed the metal-mediated induction of Cyp1a1 mRNA, but
      did not alter Cyp1a1 activity. These results clearly demonstrate that activation
      of the NF-kappaB and AP-1 signaling pathways is directly involved in the
      modulation of Cyp1a1 by heavy metals.

PMID- 18078828
TI  - A tyrosine kinase inhibitor, beta-hydroxyisovalerylshikonin, induced apoptosis in
      human lung cancer DMS114 cells through reduction of dUTP nucleotidohydrolase
      activity.
AB  - Apoptotic cell death was induced in human lung cancer DMS114 cells by treatment
      with beta-hydroxyisovalerylshikonin (beta-HIVS), an ATP-noncompetitive inhibitor
      of protein tyrosine kinases. Changes in phosphoprotein profiles were analyzed by
      two-dimensional-polyacrylamide gel electrophoresis (2D-PAGE) after the cells were
      treated with beta-HIVS. One spot on the 2D gel showed a marked decrease in
      intensity and the corresponding protein was identified by mass spectrometry as
      dUTP nucleotidohydrolase (dUTPase). The beta-HIVS-induced decrease of dUTPase in
      the phosphoprotein fraction of DMS114 cells was confirmed using immunoblotting.
      Treatment of the cells with beta-HIVS-induced rapid reduction of dUTPase
      activity. An antioxidant N-acetyl-cysteine inhibited both the reduction of
      phosphorylated dUTPase and the induction of apoptosis by beta-HIVS treatment of
      DMS114 cells. Introduction of siRNA directed against dUTPase mRNA into DMS114
      cells enhanced the susceptibility of beta-HIVS-induced apoptosis. Treatment of
      DMS114 cells with beta-HIVS and 5-fluorouracil, a specific inhibitor of
      thymidylate synthase used as a chemotherapeutic drug, revealed the synergistic
      effects of these drugs on the inhibition of cell growth. These results suggest
      that dUTPase activity is one of the crucial factors involved in apoptotic cell
      death in lung cancer cells.

PMID- 18078829
TI  - Analyses of functional interaction between RECQL1, RECQL5, and BLM which
      physically interact with DNA topoisomerase IIIalpha.
AB  - RECQL1 and RECQL5 as well as BLM reportedly interact with TOP3alpha whose defect
      is lethal for the cell. Therefore in this study, we characterized
      recql5/recql1/blm triple mutants from DT40 cells to determine whether the triple
      mutants show a top3alpha disrupted cell-like phenotype. The triple mutants are
      viable. Moreover, both blm/recql1 and recql5/blm cells, and recql5/recql1/blm
      cells grew slightly slower than blm cells, that is, triple mutant cells grew
      almost the same rate as either of the double mutant cells. The blm cells showed
      sensitivity to methyl methanesulfonate (MMS) and ultraviolet light (UV), about a
      10-fold increase in sister chromatid exchange (SCE), and about a 3-fold increase
      in damage-induced mitotic chiasma compared to wild-type cells. The triple mutants
      showed the same sensitivity to MMS or UV and the same frequency of damage-induced
      mitotic chiasma compared to those of blm cells, indicating that unlike BLM,
      RECQL1 and RECQL5 play a little role in the repair of or tolerance to DNA
      damages. However, recql5/blm cells showed higher frequency of SCE than blm cells,
      whereas the RECQL1 gene disruption had no effect on SCE in blm cells and even in
      recql5/blm cells.

PMID- 18078830
TI  - Proliferative actions of muscarinic receptors expressed in macrophages derived
      from normal and tumor bearing mice.
AB  - Macrophages (Mps) are essential cellular components of the innate immune system.
      They are released from the bone marrow as immature monocytes and after
      circulating in the blood stream, migrate into tissues to undergo final
      differentiation into resident Mps. In general terms Mps behavior in breast
      tumors, was described as being either for or against tumor growth. Under certain
      well defined circumstances Mps are able to kill cells in two ways: direct tumor
      cytotoxicity or antibody dependent cytotoxicity. We had previously demonstrated
      that peritoneal Mps from LMM3 mammary tumor bearing mice (TMps) enhanced in vivo
      the LMM3 induced angiogenesis, promoting tumor growth while Mps from normal
      BALB/c mice (NMps) did not. In this work, we demonstrate that Mps, expressing
      functional muscarinic acetylcholine receptors, are able to proliferate in vitro
      in response to the muscarinic agonist carbachol. These peritoneal cells use two
      distinct metabolic pathways: TMps are primed by tumor presence and they
      proliferate mainly by activating arginase pathway and by producing high levels of
      prostaglandin E(2) via M(1)-M(3) receptors activation. In NMps, carbachol
      stimulates M(2) receptors function, triggering protein kinase C activity and
      induces moderate prostaglandin E(2) liberation via M(1) receptor.

PMID- 18078831
TI  - Proteasome inhibition: an early or late event in nitric oxide-induced neuronal
      death?
AB  - Nitric oxide (NO), ubiquitously expressed in the central nervous system, has been
      perceived to be a potential neuromodulator. Employing cultured murine primary
      cortical neurons, NO resulted in an inhibition of the ubiquitin-proteasome system
      (UPS) with a dose- and time-dependent decrease in cell viability. This is
      consistent with a previous study that reported a dysfunction of UPS with
      consequential apoptotic death in macrophage cell with NO treatment. However, it
      cannot be unclear if the drop in UPS efficiency is directly imposed on by NO.
      Therefore by using microarray analysis, our study revealed an early down
      regulation or non-significant differential expression of genes encoding UPS
      proteins in NOC-18 (NO donor)-treated neurons as compared to an observed
      elevation of corresponding gene expression genes in lactacystin (classical
      proteasome inhibitor)-treated neurons (conducted earlier). Furthermore, time
      course analysis of proteasome activity in NOC-18-treated neurons demonstrated a
      late onset of reduction. This is intriguing as it is well established that in an
      exclusive proteasome dysfunction-induced cell death, a compensatory feedback
      mechanism will be activated with an initial and concerted up-regulation of genes
      encoding proteins involved in UPS as seen when neurons were treated with
      lactacystin. Thus, it is highly suggestive that NO-triggered neuronal death takes
      on a different signaling cascade from that of a classical proteasome inhibitor,
      and that the late reduction of proteasome activity is a downstream event
      following the activation of apoptotic cellular signaling cascade. In
      intracellular condition, the proteasome is not NO preferred primary target
      responsible for the trigger of the cell death machinery. In conclusion, we
      presented novel findings that shed light into NO-induced cell death signaling
      cascade, which would be important in understanding the pathogenesis of
      neurodegenerative disorders such as Parkinson's disease.

PMID- 18078832
TI  - Compound 48/80 induces endothelium-dependent and histamine release-independent
      relaxation in rabbit aorta.
AB  - Compound 48/80 (C48/80) is a synthetic condensation product of N-methyl-p
      methoxyphenethylamine with formaldehyde and is an experimental drug used since
      the 1950s to induce anaphylactic shock through histamine release. This study was
      carried out to further elucidate the mechanism by which this drug induces nitric
      oxide (NO) release. Our specific goals were: (a) to verify if C48/80's relaxation
      occurs through the stimulation of histamine receptors; (b) to evaluate the
      endothelium-dependent relaxation induced by C48/80; (c) to identify NO as the
      endothelium-relaxing factor released by C48/80; (d) to identify the NO synthase
      (NOS) responsible for NO release; and (e) to verify if the relaxation induced by
      C48/80 is calcium and cyclic guanidine monophosphate (cGMP) dependent. Rabbit
      aorta segments, with and without endothelium, were suspended in organ chambers
      (25ml) filled with Krebs solution maintained at 37 degrees C, bubbled with 95%
      O(2)/5% CO(2) (pH 7.4). Phenylephrine was used to contract the segments. Other
      protocol drugs included H(1)- and H(2)-receptor antagonists, cyclooxygenase, NOS,
      guanylyl cyclase and phospholipase C (PLC) inhibitors. Endothelium-dependent
      relaxation induced by C48/80 was also studied in calcium-free Krebs solution
      associated with a calcium chelator. In summary, our investigation demonstrated
      that the C48/80 vasodilating action: (a) does not depend on H(1) and H(2)
      histamine receptors; (b) is NO endothelium-dependent; (c) is dependent on the
      endothelial constitutive NOS (NOS-3) isoform activation; (d) is cGMP-dependent;
      and that NOS-3 activation by C48/80: (a) is independent of PLC up to 25mug/ml and
      (b) is partially dependent of this lipase in higher doses.

PMID- 18078827
TI  - CYP2E1 and oxidative liver injury by alcohol.
AB  - Ethanol-induced oxidative stress seems to play a major role in mechanisms by
      which ethanol causes liver injury. Many pathways have been suggested to
      contribute to the ability of ethanol to induce a state of oxidative stress. One
      central pathway seems to be the induction of cytochrome P450 2E1 (CYP2E1) by
      ethanol. CYP2E1 metabolizes and activates many toxicological substrates,
      including ethanol, to more reactive, toxic products. Levels of CYP2E1 are
      elevated under a variety of physiological and pathophysiological conditions and
      after acute and chronic alcohol treatment. CYP2E1 is also an effective generator
      of reactive oxygen species such as the superoxide anion radical and hydrogen
      peroxide and, in the presence of iron catalysts, produces powerful oxidants such
      as the hydroxyl radical. This review article summarizes some of the biochemical
      and toxicological properties of CYP2E1 and briefly describes the use of cell
      lines developed to constitutively express CYP2E1 and CYP2E1 knockout mice in
      assessing the actions of CYP2E1. Possible therapeutic implications for treatment
      of alcoholic liver injury by inhibition of CYP2E1 or CYP2E1-dependent oxidative
      stress will be discussed, followed by some future directions which may help us to
      understand the actions of CYP2E1 and its role in alcoholic liver injury.

PMID- 18078833
TI  - Edaravone prevents iNOS expression by inhibiting its promoter transactivation and
      mRNA stability in cytokine-stimulated hepatocytes.
AB  - Edaravone has an anti-inflammatory effect in experimental models of various organ
      injuries. We reported that edaravone reduces the induction of inducible nitric
      oxide synthase (iNOS) as well as pro-inflammatory cytokines in endotoxin-treated
      rats with partial hepatectomy, leading to the prevention of liver injury. Studies
      were performed to investigate the mechanisms involved in the inhibition of iNOS
      expression by edaravone in hepatocytes. Primary cultured rat hepatocytes were
      treated with interleukin (IL)-1beta in the presence or absence of edaravone, and
      iNOS and its signal were analyzed. Edaravone decreased the expression of iNOS
      mRNA and its protein stimulated by IL-1beta, resulting in the reduction of NO
      production. Edaravone inhibited the activation of transcription factor NF-kappaB
      through IkappaB degradation and the up-regulation of type I IL-1 receptor through
      PI3K/Akt activation, which are essential signals for iNOS induction. Further
      transfection experiments with iNOS promoter-luciferase construct having iNOS 3'
      UTR revealed that edaravone decreased the stability of iNOS mRNA. In support of
      this observation, edaravone decreased the expression of iNOS antisense
      transcript, which stabilizes iNOS mRNA by interacting with its 3'-UTR and RNA
      binding protein. Edaravone may inhibit the induction of iNOS gene expression at
      steps of promoter transactivation and mRNA stabilization in cytokine-stimulated
      hepatocytes.

PMID- 18078834
TI  - Proteomic investigation of the aggregation phenomenon in Lactobacillus crispatus.
AB  - Aggregation process affects the ability of Lactobacillus crispatus, a probiotic,
      to survive into the gastro-intestinal environment and to adhere to the intestinal
      mucosa. To elucidate mechanisms underlying this process, a comparative proteomic
      study was carried out on a wild type strain M247 and its spontaneous isogenic
      mutant Mu5, which had lost the aggregative phenotype. Results highlighted an
      overall lower amount of enzymes involved in carbohydrate transport and metabolism
      in strain M247 compared to strain Mu5, suggesting a reduction in the general
      growth rate, probably caused by nutrient limitation in cell aggregates,
      coherently with the phenotypic traits of the strains. Moreover, the up-regulation
      of a putative elongation factor Tu in the wild type M247 strain could suggest a
      role of this particular protein in the adhesion mechanism of L. crispatus.

PMID- 18078835
TI  - The 3' UTR of the human CTLA4 mRNA can regulate mRNA stability and translational
      efficiency.
AB  - T cell activation results from the integration of signals generated through the T
      cell antigen receptor-CD3 complex with those from additional positive and
      negative regulatory pathways mainly mediated by the engagement of costimulatory
      receptors on T cells. Disruption of this balance leads to a defective immune
      response or alternative over-activation of the immune system. CTLA-4 plays a
      critical role in downregulating T cell responses. Autoimmune diseases have shown
      genetic linkage to the CTLA4 locus. In this report we demonstrate that the 3' UTR
      of CTLA4 regulates firefly luciferase reporter gene expression, can confer
      instability to CTLA4 mRNA and can influence its translation efficiency in vitro.

PMID- 18078837
TI  - A lasp family protein of Ciona intestinalis.
AB  - Lasp-1 and lasp-2 are actin-binding proteins that contain a LIM domain, nebulin
      repeats, and an SH3 domain and they are significantly conserved in mammalian and
      avian. Lasp-1 is widely expressed in nonmuscle tissues and lasp-2 is specifically
      expressed in the brain. Genes encoding proteins homologous to lasp-1 and lasp-2
      were deposited in the genome/cDNA database of invertebrates such as sea urchins,
      nematodes, and insects; however, function of their proteins have not been studied
      in detail. In this study, we analyzed the gene structure, actin-binding activity,
      and expression of the lasp protein of the ascidian Ciona intestinalis (Ci lasp).
      A single gene encoding lasp protein was found in the ascidian, and the amino acid
      sequences of Ci lasp and other invertebrate lasp proteins exhibited similarity to
      vertebrate lasp-1 and lasp-2 to the same extent. A part of the exon-intron
      boundaries was conserved between the vertebrate lasp-1, the vertebrate lasp-2 and
      the invertebrate lasp genes. Ci lasp exhibited actin-binding activity in a co
      sedimentation assay. In situ hybridization revealed that the expression of Ci
      lasp mRNA was apparent in nervous system of early embryos and was detected in
      various tissues in young adults. This suggests that the functions of invertebrate
      lasp proteins might include the functions of vertebrate lasp-1 and lasp-2.

PMID- 18078836
TI  - Transcriptional regulation of the human soluble epoxide hydrolase gene EPHX2.
AB  - Soluble epoxide hydrolase (sEH) is a multifunctional protein encoded by the EPHX2
      gene. The biological functions and enzyme kinetics of sEH have been extensively
      investigated, however, little is known about its transcriptional regulation and
      mechanisms of tissue specific expression. Here, a luciferase gene based reporter
      assay was used to identify the minimal promoter and cis regulatory elements of
      EPHX2. The minimal promoter was identified as a GC-rich region between nts -374
      and +28 with respect to the putative transcriptional start site. A reporter
      plasmid carrying this minimal promoter showed higher or similar activities in
      comparison to a reporter plasmid carrying nts -5,974 to +28 of EPHX2 in 9 human
      cell lines that were tested. Sp1 binding sites that are involved in augmenting
      the minimal promoter activity of EPHX2 were identified by nested deletion
      analysis, site-specific mutation, electrophoretic mobility shift assay, and
      chromatin immunoprecipitation assay.

PMID- 18078838
TI  - Retinoic acid is a negative regulator of matrix Gla protein gene expression in
      teleost fish Sparus aurata.
AB  - Matrix Gla protein (MGP) is an extracellular mineral-binding protein expressed in
      several tissues while accumulated only in bone and cartilage under physiological
      conditions. Although the precise molecular mechanism of action of MGP remains
      unknown, all available evidence indicates that it acts as a physiological
      inhibitor of mineralization. This work presents the cloning of gilthead seabream
      MGP gene (SaMGP) and the functional analysis of its promoter. SaMGP gene was
      found to be organized in five exons and to be under control of a distal and a
      proximal promoter, both, capable of activating SaMGP transcription in transient
      transfections. Furthermore, we present strong evidence that retinoic acid down
      regulates SaMGP gene transcription by interacting, through binding of its
      receptor, with a specific region within distal promoter. Interestingly, the
      presence of repetitive motifs in the proximity of SaMGP gene regulatory regions
      suggests that they may modulate promoter accessibility to transcription
      machinery, as already seen for other genes. This work provides additional
      evidence of the usefulness of non-mammalian model systems to elucidate the
      complex regulation of MGP gene transcription.

PMID- 18078839
TI  - Identification of two E-boxes that negatively modulate the activity of MyoD on
      the alpha-sarcoglycan core promoter.
AB  - The alpha-SG promoter is composed of a plethora of cis-regulatory elements, whose
      individual contribution to alpha-SG gene expression modulation remains unknown.
      We have identified a negative regulatory element in the alpha-SG distal promoter
      including two conserved E-boxes (E1 and E2), which interact with MyoD. We found
      that E1 and E2 negatively modulate the transactivation potential of MyoD on the
      alpha-SG core promoter. Moreover, such negative effect is mainly mediated by E2,
      which is surrounded by conserved nucleotides conferring MyoD binding capacity.
      Our results suggest that modulation of MyoD activity by E1, and particularly E2,
      contributes to the negative regulation of alpha-SG gene expression during
      myogenic differentiation.

PMID- 18078840
TI  - Human chromosome fragility.
AB  - Fragile sites are heritable specific chromosome loci that exhibit an increased
      frequency of gaps, poor staining, constrictions or breaks when chromosomes are
      exposed to partial DNA replication inhibition. They constitute areas of chromatin
      that fail to compact during mitosis. They are classified as rare or common
      depending on their frequency within the population and are further subdivided on
      the basis of their specific induction chemistry into different groups
      differentiated as folate sensitive or non-folate sensitive rare fragile sites,
      and as aphidicolin, bromodeoxyuridine (BrdU) or 5-azacytidine inducible common
      fragile sites. Most of the known inducers of fragility share in common their
      potentiality to inhibit the elongation of DNA replication, particularly at
      fragile site loci. Seven folate sensitive (FRA10A, FRA11B, FRA12A, FRA16A, FRAXA,
      FRAXE and FRAXF) and two non-folate sensitive (FRA10B and FRA16B) fragile sites
      have been molecularly characterized. All have been found to represent expanded
      DNA repeat sequences resulting from a dynamic mutation involving the normally
      occurring polymorphic CCG/CGG trinucleotide repeats at the folate sensitive and
      AT-rich minisatellite repeats at the non-folate sensitive fragile sites. These
      expanded repeats were demonstrated, first, to have the potential, under certain
      conditions, to form stable secondary non-B DNA structures (intra-strand hairpins,
      slipped strand DNA or tetrahelical structures) and to present highly flexible
      repeat sequences, both conditions which are expected to affect the replication
      dynamics, and second, to decrease the efficiency of nucleosome assembly,
      resulting in decondensation defects seen as fragile sites. Thirteen aphidicolin
      inducible common fragile sites (FRA2G, FRA3B, FRA4F, FRA6E, FRA6F, FRA7E, FRA7G,
      FRA7H, FRA7I, FRA8C, FRA9E, FRA16D and FRAXB) have been characterized at a
      molecular level and found to represent relatively AT-rich DNA areas, but without
      any expanded repeat motifs. Analysis of structural characteristics of the DNA at
      some of these sites (FRA2G, FRA3B, FRA6F, FRA7E, FRA7G, FRA7H, FRA7I, FRA16D and
      FRAXB) showed that they contained more areas of high DNA torsional flexibility
      with more highly AT-dinucleotide-rich islands than neighbouring non-fragile
      regions. These islands were shown to have the potential to form secondary non-B
      DNA structures and to interfere with higher-order chromatin folding. Therefore, a
      common fragility mechanism, characterized by high flexibility and the potential
      to form secondary structures and interfere with nucleosome assembly, is shared by
      all the cloned classes of fragile sites. From the clinical point of view, the
      folate sensitive rare fragile site FRAXA is the most important fragile site as it
      is associated with the fragile X syndrome, the most common form of familial
      mental retardation, affecting about 1/4000 males and 1/6000 females. Mental
      retardation in this syndrome is considered as resulting from the abolition of the
      FMR1 gene expression due to hypermethylation of the gene CpG islands adjacent to
      the expanded methylated trinucleotide repeat. FRAXE is associated with X-linked
      non-specific mental retardation, and FRA11B with Jacobsen syndrome. There is also
      some evidence that fragile sites, especially common fragile sites, are
      consistently involved in the in vivo chromosomal rearrangements related to
      cancer, whereas the possible implication of common fragile sites in
      neuropsychiatric and developmental disorders is still poorly documented.

PMID- 18078841
TI  - Molecular cloning and functional analysis of an ERF gene from cotton (Gossypium
      hirsutum).
AB  - Ethylene response factors (ERFs) play important roles in regulating plant biotic
      and abiotic stress tolerance. In this paper, a new ethylene response factor gene
      GhERF1 was isolated from cotton. The deduced amino acid sequence of GhERF1
      contained an AP2/ERF domain, which shared high similarity with other reported
      AP2/ERF domains and was most closely related to the B3 subgroup of the ERF
      subfamily. The particle bombardment assay showed that GhERF1 functioned as an in
      vivo transcription activator in tobacco cells and was localized in the nuclei of
      onion epidermis cells. In addition, semi-quantitative RT-PCR revealed that GhERF1
      accumulated highly and rapidly when plants were treated with exogenous ethylene,
      abscisic acid (ABA), high salinity, cold and drought. These results suggested
      that GhERF1 might be functionally important in acclimation of cotton to stress.

PMID- 18078843
TI  - Small RNAs in tomato fruit and leaf development.
AB  - Tomato fruit and leaf development offers excellent systems to study the evolution
      of gene regulation underlying development of different organs. We have identified
      over 350 and 700 small RNAs from tomato fruit and leaf, respectively. Except for
      conserved microRNAs, more than 90% of the small RNAs are unique to tomato. We
      confirmed expression of some conserved as well as novel putative microRNAs by
      Northern hybridization. Our results help form a basis for comparative studies on
      how small RNA-mediated gene expression has contributed to the evolution of common
      and distinct developmental pathways of fruits and leaves. We have established a
      website (http://ted.bti.cornell.edu/digital/sRNA/) for public access to all of
      our small RNA sequences, their expression patterns in respective tissues, and
      their matching genes or predicted target genes in a searchable manner.

PMID- 18078845
TI  - In brief. Management of the trauma patient.

PMID- 18078842
TI  - RNA recognition by 3'-to-5' exonucleases: the substrate perspective.
AB  - The 3'-to-5' exonucleolytic decay and processing of a variety of RNAs is an
      essential feature of RNA metabolism in all cells. The 3'-5' exonucleases, and in
      particular the exosome, are involved in a large number of pathways from 3'
      processing of rRNA, snRNA and snoRNA, to decay of mRNAs and mRNA surveillance.
      The potent enzymes performing these reactions are regulated to prevent processing
      of inappropriate substrates whilst mature RNA molecules exhibit several
      attributes that enable them to evade 3'-5' attack. How does an enzyme perform
      such selective activities on different substrates? The goal of this review is to
      provide an overview and perspective of available data on the underlying
      principles for the recognition of RNA substrates by 3'-to-5' exonucleases.

PMID- 18078846
TI  - Pitfalls in the evaluation and management of the trauma patient.

PMID- 18078847
TI  - Restricting access of human immunodeficiency virus (HIV)-seropositive patients to
      infertility services: a legal analysis of the rights of reproductive
      endocrinologists and of HIV-seropositive patients.
AB  - OBJECTIVE: To discuss the legal rights of reproductive endocrinologists and HIV
      seropositive patients seeking infertility services. DESIGN: Westlaw and
      LexisNexis commercial legal search engines were used to perform a legal review of
      statutes and cases pertaining to HIV-seropositive patients seeking health care
      services. CONCLUSION(S): Human immunodeficiency virus antidiscrimination laws
      apply to healthcare providers whether they practice in private clinics or a
      university setting. Patients infected with HIV cannot be denied access to health
      services solely on the basis of their HIV status. If proof exists that HIV
      seropositive patients will medically benefit by a referral to another provider
      with more expertise, it is legally permissible to refer these patients to another
      provider who has more expertise in providing infertility services to HIV
      seropositive patients. However, the burden will be on the reproductive
      endocrinologist to demonstrate that he or she lacks the capability to care for
      HIV-seropositive patients and that the referral was for the medical benefit of
      the patient and of the patient's potential offspring.

PMID- 18078848
TI  - Effect of the Lebanese civil war on sperm parameters.
AB  - OBJECTIVE: To assess the effect of the Lebanese civil war on sperm parameters.
      DESIGN: Retrospective review of patient records. SETTING: Males providing semen
      samples at a university laboratory. Semen samples collected 1985-1989 (during the
      war) were compared with those obtained 1991-1995 (postwar). PATIENT(S): Males
      with or without a history of infertility providing semen samples at a university
      central laboratory. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Standard
      clinical semen analysis. RESULT(S): The sperm concentration was significantly
      lower during the war compared with the postwar period. However, the percentage of
      abnormal sperm morphology increased in the postwar period. War had no significant
      effect on volume and motility. Postwar, the percent azospermic and those <10
      million remained the same, but there was a shift in the count from the borderline
      count (11-20 million) to normal (>20 million). CONCLUSION(S): There was a
      significant decline in sperm concentration during the Lebanese civil war.
      Increased stress level during the war is believed to be one of the main factors
      leading to this finding.

PMID- 18078849
TI  - Premature ovarian failure in suspected Whipple's disease.
AB  - INTRODUCTION: Whipple's disease is a relapsing systemic infectious disease
      probably caused by the Gram-positive bacillus Tropheryma whippelii. The diagnosis
      can be established based on the characteristic histopathological features found
      in the affected organ (foamy macrophages with a coarsely granular cytoplasm,
      which stains with PAS, and by means of polymerase chain reaction (PCR)
      technology). CASE REPORT: We report a case of a 23-year-old woman affected by
      suspected Whipple's disease. She presented encephalopathy and neuropathy with
      inveterate hyperpyrexia and alteration of the hypothalamic-pituitary-ovary axe.
      She was amenorrheic because of an hypergonadotropic hypogonadism. DISCUSSION:
      This hypogonadism is possibly due to follicular depletion caused by inveterate
      hyperpyrexia or T. whipplii localization.

PMID- 18078850
TI  - Reassessing the value of varicocelectomy as a treatment for male subfertility
      with a new meta-analysis.

PMID- 18078851
TI  - Diagnostic ability of the Heidelberg Retina Tomograph 3 for glaucoma.
AB  - PURPOSE: To compare the diagnostic ability of the Heidelberg Retina Tomograph 3
      (HRT3) and the Heidelberg Retina Tomograph 2 (HRT2) for discriminating between
      healthy eyes and eyes with glaucomatous visual field loss. DESIGN: Retrospective
      cross-sectional study. METHODS: Participants were 93 healthy subjects and 90
      patients with open-angle glaucoma. All participants underwent imaging of the
      optic nerve head with the HRT2. Afterward, HRT data also were analyzed using
      version 3 of the software without modifying the optic disk contour line. The
      receiver operating characteristic (ROC) curves between normal and glaucomatous
      subjects were plotted for the global stereometric parameters of both software
      versions. Moorfields regression analysis (MRA) and glaucoma probability score
      (GPS) diagnostic abilities also were compared. RESULTS: The parameters with the
      largest areas under the ROC curve were the Frederick S. Mikelberg (FSM)
      discriminant function for the HRT3 (0.948) and the vertical cup-to-disk ratio
      (0.914) for the HRT2. At a fixed specificity of 95%, the best sensitivity was
      74.4% for the Reinhard O.W. Burk (RB) discriminant function of the HRT2 and 83.3%
      for the FSM discriminant function of the HRT3. The best sensitivity and
      specificity pairs for the HRT classifications were 85.5% and 76.3%, respectively,
      for overall MRA2, 84.4% and 83.8%, respectively, for overall MRA3, 93.3% and
      58.0%, respectively, for the global color-coded GPS, and 84.4% and 74.1%,
      respectively, for the global GPS numerical value. CONCLUSIONS: At 95% fixed
      specificity, most HRT3 parameters exhibited at least the same sensitivity for
      glaucoma diagnosis as the analogous parameters for the HRT2. The diagnostic
      ability overall of MRA3 was similar to that of the previous version. GPS
      exhibited higher sensitivity and somewhat lower specificity than the MRA.

PMID- 18078852
TI  - A visual field index for calculation of glaucoma rate of progression.
AB  - PURPOSE: To present a new perimetric index for calculating the rate of
      glaucomatous progression and to compare its performance with the traditional mean
      deviation index (MDI). DESIGN: Experimental study describing a device and
      retrospective cohort study. METHODS: We developed a new visual field index, the
      glaucoma progression index (GPI), intended to be less affected by cataract than
      the MDI by calculating age-corrected defect depth at test points identified as
      significantly depressed in pattern deviation probability maps. The valid
      operating range for pattern deviation analysis was estimated. When exceeding this
      range, the total deviation probability maps were used for identification of
      significantly depressed points. The GPI is expressed in percentage, where 100%
      represents a normal visual field and 0% represents a perimetrically blind field,
      and is plotted vs patient age. Rate of progression, presented as yearly change in
      the GPI, is calculated by linear regression analysis. We conducted a pilot
      evaluation in three groups of patients: 1) eyes with developing cataract, 2) eyes
      without cataract, and 3) eyes in which cataract surgery was performed in the
      middle of the series. RESULTS: The cut-off for pattern deviation was, at mean
      deviation, worse than -20 decibels (dB) in fields in which the eighty-fifth
      percentile of the total deviation value was significantly depressed. In the first
      group (n = 45), the measured rate of progression was greater with the MDI than
      with the GPI (P < .0001). The mean loss per year was 3.6%/year for the MDI and
      2.1%/year for the GPI. In the second group (n = 42), the rate of progression did
      not differ between the MDI and the GPI (P = .52); the means were 2.7%/year and
      2.6%/year, respectively. In the third group (n = 44), the confidence limits for
      the rate of progression were significantly smaller with the GPI than with the MDI
      (P = .04). CONCLUSIONS: Glaucoma progression rates calculated using the GPI seem
      to be considerably less affected by cataract and cataract surgery than rates
      based on the traditional MDI.

PMID- 18078854
TI  - L-arginine metabolism in dog kidney and isolated nephron segments.
AB  - The renal basic amino acid metabolism often differs in rodents, strict
      carnivores, and omnivore species. Given the pivotal role of L-arginine and L
      ornithine in several metabolic pathways and the fact that the dog is closely
      related to humans, being also an omnivore, we tested whether L-arginine
      metabolism and L-ornithine catabolism take place in the dog kidney. We examined
      the metabolism of L-arginine in dog cortical tubules to integrate local L
      arginine metabolism into a general physiological and metabolic framework. To
      achieve these goals, we first ascertained the protein expression of relevant
      enzymes by Western blot. L-Arginine catabolism was studied in suspensions of
      canine cortical proximal tubules, medullary thick ascending limbs, and papillary
      collecting ducts either incubated without exogenous L-arginine being added (small
      endogenous quantities) or incubated with L-arginine being added in
      supraphysiological amounts (2 mmol/L with or without the presence of alternative
      metabolic substrates, 2 mmol/L L-glutamine, or lactate). The results revealed
      that dog kidneys consumed L-citrulline and released L-arginine and L-ornithine.
      Argininosuccinate synthetase and lyase, arginase II, and ornithine
      aminotransferase were detected in the renal cortex. Arginase II activity was
      found in a suspension of proximal tubules by measuring the amounts of urea and L
      ornithine produced. A fraction of this L-ornithine was further partially
      metabolized through the intramitochondrial ornithine aminotransferase pathway,
      leading to changes in L-glutamate, glucose, L-alanine, and ammonia metabolism
      without L-proline accumulation. Medullary thick ascending limbs expressed a very
      low arginase activity, whereas papillary collecting ducts did not. In conclusion,
      the dog kidney produces L-arginine. Part of this L-arginine is further
      catabolized by arginase II, suggesting that its physiological role was to produce
      L-ornithine for the body.

PMID- 18078853
TI  - Effects of short-term very low-calorie diet on intramyocellular lipid and insulin
      sensitivity in nondiabetic and type 2 diabetic subjects.
AB  - The study aimed to analyze the effects of a short-term very low-calorie diet
      (VLCD) on intramyocellular lipid (IMCL), total body fat, and insulin sensitivity
      in a group of obese nondiabetic and type 2 diabetic subjects. Seven untreated
      type 2 diabetic and 5 obese nondiabetic individuals were studied before and after
      a 6-day VLCD using proton magnetic resonance spectroscopy to quantify IMCL, dual
      energy x-ray absorptiometry to assess body fat, and hyperinsulinemic-euglycemic
      clamps to measure peripheral insulin sensitivity. In both groups, decrements in
      total body fat mass and body mass index were small but statistically significant.
      In contrast, the diet resulted in a pronounced reduction in IMCL compared with
      baseline values in nondiabetic subjects (56% decrease) and type 2 diabetic
      subjects (40% decrease) (P < .05), and this was accompanied by an overall 9.3%
      increase in maximally stimulated glucose disposal rate (P < .01).
      Intramyocellular lipid was significantly correlated with insulin sensitivity (r =
      -0.69, P < .01) and waist circumference (r = 0.72 and 0.83, baseline and
      postdiet, respectively; both P < .01), but neither IMCL nor insulin sensitivity
      was related to measures of general adiposity such as body mass index, percentage
      of body fat, or total body fat (P = not significant). In conclusion, short-term
      VLCD is accompanied by small decrements in general adiposity, marked decrease in
      IMCL, and an increase in insulin sensitivity in nondiabetic and type 2 diabetic
      subjects. Therefore, rapid amelioration of insulin resistance by VLCD can be
      partially explained by loss of IMCL both in nondiabetic and type 2 diabetic
      subjects in the absence of substantial changes in total body fat. These
      observations are consistent with the idea that insulin resistance is more
      directly related to IMCL rather than to body fat per se.

PMID- 18078855
TI  - Impaired fasting glucose and the prevalence and severity of angiographic coronary
      artery disease in high-risk Chinese patients.
AB  - We assessed the relation between different fasting plasma glucose (FPG) levels of
      5.6 to 6.9 mmol/L and the prevalence and severity of angiographic coronary artery
      disease (CAD) in high-risk Chinese patients. Among 512 subjects who were to
      undergo coronary angiography for the confirmation of suspected myocardial
      ischemia, 409 subjects were enrolled and categorized into 3 groups based on FPG
      levels: (1) </=5.5 mmol/L, (2) 5.6 to 6.0 mmol/L, and (3) 6.1 to 6.9 mmol/L. Each
      of these groups was further divided into subgroups by sex; the second and third
      groups were combined as an additional group according to the 2003 definition of
      impaired fasting glucose (FPG at 5.6-6.9 mmol/L). We analyzed the coronary artery
      stenosis score, the prevalence of angiographic CAD, and the percentage of
      stenosis in the 3 main arteries among the groups and examined the risk factors
      for angiographic CAD prevalence by logistic regression analysis. A higher
      correlation was observed between angiographic CAD prevalence and FPG levels of
      6.1 to 6.9 mmol/L as compared with FPG levels </=5.5 mmol/L (adjusted odds ratio
      [OR], 2.67; 95% confidence interval [CI], 1.72-4.10; P = .011). The FPG levels of
      5.6 to 6.9 mmol/L (adjusted OR, 2.57; 95% CI, 1.65-4.02; P < .001) and 5.6 to 6.0
      mmol/L (adjusted OR, 2.33; 95% CI, 1.58-3.49; P = .008) were modestly correlated
      with angiographic CAD prevalence. The angiographic CAD prevalence, coronary
      artery stenosis score, and the percentage of stenosis in the left anterior
      descending branch increased corresponding to increasing FPG levels from </=5.5
      mmol/L to 5.6 to 6.0 mmol/L to 6.1 to 6.9 mmol/L. We concluded that FPG levels of
      5.6 to 6.9 mmol/L as well as of 6.1 to 6.9 mmol/L may be an independent risk
      factor for angiographic CAD; furthermore, there was a progressive and graded
      relation between FPG levels of 5.6 to 6.9 mmol/L and angiographic CAD prevalence
      and severity in high-risk Chinese patients.

PMID- 18078856
TI  - Biphasic insulin secretion from freshly isolated or cultured, perifused rodent
      islets: comparative studies with rats and mice.
AB  - In the present report, we compared the insulin secretory responses of freshly
      isolated, perifused rat and mouse islets to glucose. Prestimulatory glucose
      levels were changed to assess their influence on the subsequent secretory
      responses. Additional studies included experiments with the incretin factor
      glucagon-like peptide-1 (GLP-1), the cholinergic agonist carbachol, and the
      alpha2 agonist epinephrine. Our findings demonstrate that under conditions where
      glucose (8.5-11.1 mmol/L) evokes a dramatic biphasic insulin secretory response
      from perifused rat islets, mouse islets exhibit little response. Increasing the
      prestimulatory glucose level to 8.5 mmol/L dramatically distorts subsequently
      measured glucose-induced insulin secretion from rat islets but allows the
      evocation of a modest but clear biphasic response from mouse islets in response
      to 30 mmol/L, but not 11.1 or 16.7 mmol/L, glucose. In the presence of a
      minimally effective glucose level (10 mmol/L), mouse islets remain exquisitely
      sensitive to the combined stimulatory effects of GLP-1 (2.5 nmol/L) plus
      carbachol (0.5 micromol/L) and to the inhibitory influence of epinephrine (10
      nmol/L). Short-term culture of rat islets in CMRL 1066 containing 5.6 mmol/L
      glucose resulted in a significant decrease in the secretory response to 11.1
      mmol/L glucose, whereas the same manipulation improved mouse islet responses. It
      is concluded that the process of collagenase isolating islets does not alter
      mouse islet sensitivity in any adverse way and that increasing the prestimulatory
      glucose level can indeed alter the pattern of insulin secretion in either a
      positive or negative manner depending upon the species being investigated. Prior
      short-term culture of rodent islets differentially affects secretion from these 2
      species.

PMID- 18078857
TI  - Leptin but not neuropeptide Y up-regulated glucagon-like peptide 1 receptor
      expression in GT1-7 cells and rat hypothalamic slices.
AB  - In an attempt to gain better insight into the central effects of glucagon-like
      peptide (GLP-1), we studied the action of glucose and of regulatory peptides on
      the expression of its receptor (GLP-1R) in hypothalamic GT1-7 cells and in
      ventromedial (VMH) and lateral (LH) rat hypothalamus slices. The promoter
      activity of GLP-1R in transfected GT1-7 cells increased with leptin, whereas
      neuropeptide Y (NPY) did not modify it. Interestingly, when cells were incubated
      with both NPY and leptin, NPY blocked the stimulating effect of leptin. The
      effects of leptin and NPY were also confirmed at messenger RNA levels. In
      hypothalamic slices, GLP-1R messenger RNA levels increased at higher glucose
      concentrations in the VMH. In addition, leptin exerted a stimulating effect; and
      NPY did not modify receptor expression. By contrast, in the LH, the opposite
      effects were found for those parameters, except at 20 mmol/L glucose. These
      findings suggest that the stimulating effect of leptin on GLP-1R expression, with
      no changes in NPY-induced activity, could enhance the anorexic actions generated
      through this receptor. In addition, the different responses of the VMH and LH may
      be related to specific functions of these structures, as already known in vivo,
      highlighting the interest of hypothalamic slices for this kind of study.

PMID- 18078858
TI  - Metabolic syndrome: do clinical criteria identify similar individuals among
      overweight premenopausal women?
AB  - The purpose of this analysis was to determine to what extent the clinical
      criteria for metabolic syndrome (MetSyn) proposed by the World Health
      Organization (WHO), the European Group for Study of Insulin Resistance (EGIR),
      the National Cholesterol Education Program Adult Treatment Panel III (ATP III),
      and the International Diabetes Foundation (IDF); triglyceride (TG)/high-density
      lipoprotein cholesterol (HDL-C) ratio >/=3.0; and enlarged waist circumference
      (>/=88 cm) and elevated TG (>/=129 mg/dL) (EWET) identified similar or different
      overweight women and, secondarily, to examine the effect of 7% weight reduction
      on MetSyn status. Metabolic syndrome was determined among 256 premenopausal women
      (age = 41 +/- 6 years, body mass index [BMI] = 32 +/- 4 kg/m(2)) participating in
      a dietary weight loss clinical trial based on the clinical criteria proposed by
      WHO, EGIR, ATP III, and IDF. The prevalence of TG/HDL-C ratio >/=3.0 and EWET was
      determined and compared with MetSyn status. Based on the clinical criteria, 16.1%
      (EGIR), 20.7% (WHO), 31.0% (ATP III), and 31.8% (IDF) of participants met the
      criteria for MetSyn; 30.3% and 31.8% had TG/HDL-C >/=3.0 and EWET, respectively.
      Between 77% and 99% of participants were similarly classified across the clinical
      criteria. The highest and lowest agreements were between ATP III and IDF (kappa =
      0.98; 95% confidence interval, 0.96-1.0) and WHO and IDF (kappa = 0.39; 95%
      confidence interval, 0.26-0.51), respectively. The TG/HDL-C ratio >/=3.0 and EWET
      moderately agreed with all 4 clinical criteria for MetSyn (kappa range, 0.36
      0.59). Among those diagnosed with MetSyn at baseline, 64.0% to 75.0% of the
      participants who lost >/=7% and 25.8% to 55.6% of participants who lost <7% of
      their baseline body weight in 6 months no longer met the various clinical
      criteria for MetSyn, TG/HDL-C >/=3.0, or EWET. Our findings indicate that MetSyn
      varies substantially between clinical criteria, which raise questions about the
      clinical utility of these criteria. Regardless of MetSyn clinical criteria, >/=7%
      reduction in body weight has a beneficial impact on variables used to define
      MetSyn.

PMID- 18078859
TI  - Statin modulates insulin signaling and insulin resistance in liver and muscle of
      rats fed a high-fat diet.
AB  - Recent studies have shown that statins might have relevant effects on insulin
      resistance in animal models and in humans. However, the molecular mechanisms that
      account for this improvement in insulin sensitivity are not well established. The
      aim of the present study was to investigate the effect of a statin on insulin
      sensitivity and insulin signaling in liver and muscle of rats fed on a high-fat
      diet (HFD) for 4 weeks, treated or not with lovastatin during the last week. Our
      data show that treatment with lovastatin results in a marked improvement in
      insulin sensitivity characterized by an increase in glucose disappearance rate
      during the insulin tolerance test. This increase in insulin sensitivity was
      associated with an increase in insulin-induced insulin receptor (IR) tyrosine
      phosphorylation and, in parallel, a decrease in IR serine phosphorylation and
      association with PTP1B. Our data also show that lovastatin treatment was
      associated with an increase in insulin-stimulated insulin receptor substrate
      (IRS) 1/phosphatidylinositol 3-kinase/Akt pathway in the liver and muscle of HFD
      fed rats in parallel with a decrease in the inflammatory pathway (c-jun N
      terminal kinase and I kappa beta kinase (IKKbeta)/inhibitor of kappaB/nuclear
      factor kappaB) related to insulin resistance. In summary, statin treatment
      improves insulin sensitivity in HFD-fed rats by reversing the decrease in the
      insulin-stimulated IRS-1/phosphatidylinositol 3-kinase/Akt pathway in liver and
      muscle. The effect of statins on insulin action is further supported by our
      findings that HFD rats treated with statin show a reduction in IRS-1 serine
      phosphorylation, I kappa kinase (IKK)/inhibitor of kappaB/nuclear factor kappaB
      pathway, and c-jun N-terminal kinase activity, associated with an improvement in
      insulin action. Overall, these results provide important new insight into the
      mechanism of statin action in insulin sensitivity.

PMID- 18078860
TI  - High-sensitivity C-reactive protein level is a significant risk factor for silent
      cerebral infarction in patients on hemodialysis.
AB  - In patients with chronic renal failure on hemodialysis (HD), silent cerebral
      infarctions (SCIs) are associated with high mortality. The levels of high
      sensitivity C-reactive protein (HSCRP), a marker of inflammation and
      atherosclerosis, elevate with increasing renal dysfunction. We tested the
      hypothesis that increased HSCRP levels correlate with the occurrence of SCI in HD
      patients. By brain magnetic resonance imaging findings, we divided 54 patients
      undergoing HD into a with-SCI group (61 +/- 8 years, n = 30) and a without-SCI
      group (60 +/- 7 years, n = 24). We compared sex, body mass index, metabolic
      profiles, HSCRP levels, and smoking habits in Japanese patients on HD with and
      without SCI. We made the following observations: (1) The number of patients with
      diabetes or hypertension did not differ between the 2 groups. (2) The levels of
      HSCRP were higher in the with-SCI group in comparison with the without-SCI group
      (P < .0001). (3) The proportion of smokers was higher in the with-SCI group than
      in the without-SCI group (P < .05). (4) Plasma levels of high-density lipoprotein
      cholesterol were lower, whereas uric acid was higher, in the with-SCI group than
      in the without-SCI group (P < .05 and P < .0001, respectively). (5) Multivariate
      logistic analysis identified HSCRP levels as being significantly associated with
      the presence of SCI (odds ratio, 1.61; 95% confidence interval, 1.17-2.85; P <
      .001). This study indicates that patients in chronic renal failure who are
      maintained on HD exhibit an increased prevalence of SCI and that HSCRP is
      significantly associated with the presence of SCI in HD patients.

PMID- 18078861
TI  - Association between serum uric acid and the Adult Treatment Panel III-defined
      metabolic syndrome: results from a single hospital database.
AB  - Hyperuricemia is known to be associated with various metabolic abnormalities of
      the metabolic syndrome, but its precise contribution is not well defined. We have
      investigated the effects of serum uric acid on the metabolic syndrome as defined
      by the Adult Treatment Panel (ATP) III criteria and tested its independent
      association. This was a cross-sectional study consisting of 1686 Korean subjects
      (821 men and 865 women) from a health promotion center. Clinical data and the
      presence of the metabolic syndrome were assessed, and serum uric acid was tested
      for its independent contribution to the metabolic syndrome using 2 multiple
      logistic regression models. The metabolic syndrome was defined by the original
      ATP III criteria and the modified ATP III criteria that include a reduced waist
      circumference. The general age-adjusted prevalence of the metabolic syndrome was
      4.4% in men and 6.8% in women; hyperuricemic subjects tended to have a higher
      prevalence of the metabolic syndrome and more metabolic abnormalities than
      normouricemic subjects. The prevalence of the metabolic syndrome increased as
      normouricemia (2.9%) progressed to hyperuricemia (8.9%) and to gout (43.6%) in
      men. Multivariate analysis showed that serum uric acid was a significant factor
      for the development of the metabolic syndrome as defined by the original ATP III
      criteria only in one model for women (odds ratio, 1.51; 95% confidence interval,
      1.11-2.05; P = .009). Serum uric acid is closely linked to and may even be
      independently associated with the metabolic syndrome as defined by the ATP III
      criteria, but only in women.

PMID- 18078862
TI  - Relation of gemfibrozil treatment and high-density lipoprotein subpopulation
      profile with cardiovascular events in the Veterans Affairs High-Density
      Lipoprotein Intervention Trial.
AB  - The significant cardiovascular disease (CVD) event reduction in the Veterans
      Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) could not be fully
      explained by the 6% increase in high-density lipoprotein (HDL) cholesterol with
      the fibrate gemfibrozil. We examined whether measurement of HDL subpopulations
      provided additional information relative to CVD risk reduction. The HDL
      subpopulations were characterized by 2-dimensional gel electrophoresis in
      subjects who were treated with gemfibrozil (n = 754) or placebo (n = 741). In
      this study, samples obtained at the 3-month visit were used; and data were
      analyzed prospectively using CVD events (coronary heart disease death, myocardial
      infarction, or stroke) during the 5.1 years of follow-up. Analyses in the
      gemfibrozil arm showed that subjects with recurrent CVD events had significantly
      higher prebeta-1 and had significantly lower alpha-1 and alpha-2 HDL levels than
      those without such events. Prebeta-1 level was a significant positive predictor;
      alpha-1 and alpha-2 levels were significant negative risk factors for future CVD
      events. alpha-2 level was superior to HDL cholesterol level in CVD-risk
      assessment after adjustment for established risk factors. Gemfibrozil treatment
      was associated with 3% to 6% decreases in the small, lipid-poor prebeta-1 HDL and
      in the large, lipid-rich alpha-1 and alpha-2 HDL and with increases in the small
      alpha-3 (3%) and prealpha-3 (16%) HDLs. Although the use of gemfibrozil has been
      associated with reduction in CVD events in VA-HIT, HDL subpopulation analysis
      indicates that gemfibrozil-mediated improvement in CVD risk might not be the
      result of its effects on HDL. It is quite possible that much of the
      cardiovascular benefits of gemfibrozil are due to a much wider spectrum of
      effects on metabolic processes that is not reflected by changes in blood lipids
      and HDL subpopulations.

PMID- 18078864
TI  - Divergent effects of hyper- and hypoglycemia on circulating vascular endothelial
      growth factor in humans.
AB  - Vascular endothelial growth factor (VEGF) is known to be up-regulated by hypoxia,
      hyperglycemia, and hypoglycemia in vitro. In contrast, it has been found in
      healthy humans that plasma concentrations of VEGF decrease upon hypoxia under in
      vivo conditions, indicating that systemic VEGF concentration may be differently
      regulated than cellular expression. To test the effect of blood glucose levels on
      VEGF concentrations in vivo, we examined plasma VEGF changes upon brief hyper-
      and hypoglycemia in healthy male subjects. We rapidly induced in a crossover
      design hypoglycemia by insulin bolus application of 0.1 U/kg or hyperglycemia by
      dextrose infusion in 24 healthy young men. Plasma VEGF concentrations were
      measured at baseline, at the target glucose concentration of <2.2 mmol/L or >10
      mmol/L, and after further 5 and 10 minutes. Plasma VEGF concentrations decreased
      upon hyperglycemia as compared with euglycemic baseline (P = .027), whereas
      during hypoglycemic condition, there was a trend for an increase (P = .091).
      Analysis for repeated measurements including both conditions revealed a
      differential regulation of plasma VEGF levels upon glycemic condition (P = .035).
      Our results are consistent with the hypothesis that systemic VEGF concentration
      may be differentially regulated than expression on cellular basis. Because VEGF
      is a candidate hormone for regulating glucose passage across the blood-brain
      barrier under critical conditions, it possibly acts as a neuroprotective
      controller for constant cerebral glucose supply. This may be of relevance for the
      understanding of VEGF alterations in different pathological states such as
      diabetes mellitus.

PMID- 18078863
TI  - Evidence for pancreatic beta-cell dysfunction in brothers of women with
      polycystic ovary syndrome.
AB  - Hyperandrogenemia and insulin resistance are heritable traits in sisters of women
      with polycystic ovary syndrome (PCOS). Hyperandrogenemia also appears to be the
      male reproductive phenotype; however, it is less clear whether male relatives are
      at risk for the metabolic disorders associated with PCOS. In this study, we
      tested the hypothesis that brothers of women with PCOS have defects in insulin
      action and/or secretion. Twenty-three non-Hispanic white brothers of women with
      PCOS and 23 non-Hispanic white control men of comparable age matched for body
      mass index underwent a modified frequently sampled intravenous glucose tolerance
      test. Parameters of insulin sensitivity and secretion were determined using
      minimal-model Bergman protocol. Disposition index was significantly decreased
      (2540 [1080, 3172] vs 2901 [2096, 4487], P = .009) independent of a family
      history of diabetes mellitus, and glucose effectiveness was significantly
      increased (2.4 [1.9, 2.7] vs 2.0 [1.8, 2.2], P = .02) in brothers compared with
      control men. We conclude that brothers of women with PCOS have evidence for
      pancreatic beta-cell dysfunction and may be at increased risk for type 2 diabetes
      mellitus.

PMID- 18078865
TI  - Linear growth in relation to the circulating concentrations of insulin-like
      growth factor I, parathyroid hormone, and 25-hydroxy vitamin D in children with
      nutritional rickets before and after treatment: endocrine adaptation to vitamin D
      deficiency.
AB  - The objective of the study was to determine the degree of linear growth
      retardation of patients with vitamin D deficiency rickets at presentation and the
      magnitude of catch-up growth in relation to their calcium (Ca) homeostasis and
      hormones affecting it before and after treatment. This prospective study recorded
      the anthropometric data and measured the circulating 25-hydroxy vitamin D (25-OH
      D), insulin-like growth factor I (IGF-I), parathyroid hormone, Ca, phosphate, and
      alkaline phosphatase concentrations in 46 infants and children with nutritional
      (vitamin D deficiency) rickets before and 6 months or more after treatment with
      one intramuscular injection of vitamin D3 megadose (300000 IU). Forty normal age-
      and sex-matched children were included as controls for the auxological data. At
      presentation, patients' mean age = 13.1 +/- 1.1 months, length standard deviation
      scores (LSDS) = -1.5 +/- 0.2, and body mass index = 16.3 +/- 0.85. They were
      significantly shorter and had markedly lower growth velocity standard deviation
      scores (GVSDS) compared with normal controls (LSDS = 0.25 +/- 0.18 and 0.31 +/-
      0.22, respectively). Six months after treatment, the LSDS increased significantly
      in patients to -0.45 +/- 0.13, with a significantly increased GVSDS (2.76 +/-
      0.45) and body mass index (16.9 +/- 0.65). They were still shorter but with
      significantly higher GVSDS compared with normal controls. Serum Ca and phosphate
      concentrations increased from 2.07 +/- 0.25 and 1.23 +/- 0.24 mmol/L,
      respectively, before treatment to 2.44 +/- 0.2 and 1.94 +/- 0.2 mmol/L,
      respectively, after treatment. Serum alkaline phosphatase and parathyroid hormone
      concentrations decreased from 1183 +/- 219 U/L and 294 +/- 87 pg/mL,
      respectively, before treatment to 334 +/- 75 U/L and 35.2 +/- 15.2 pg/mL,
      respectively, after treatment. The 25-OH-D level increased from 4.5 +/- 0.56
      ng/mL before treatment to 44.5 +/- 3.7 ng/mL after treatment. Circulating
      concentrations of IGF-I increased significantly after treatment (52.2 +/- 18.9
      ng/mL) vs before treatment (26.6 +/- 12.8 ng/mL). The 25-OH-D concentrations were
      correlated significantly with the IGF-I levels before and after treatment (r =
      0.603 and r = 0.59, respectively; P < .001). The GVSDS after treatment was
      correlated with the increase of IGF-I and 25-OH-D levels (r = 0.325 and r= 0.314,
      respectively; P < .01). These data denote that the accelerated linear growth
      after treatment of nutritional vitamin D deficiency is mediated through
      activation of the growth hormone/IGF-I system and suggests an important role of
      vitamin D as a link between the proliferating cartilage cells of the growth plate
      and growth hormone/IGF-I secretion. Three different sequential stages of vitamin
      D deficiency can be recognized according to the clinical/radiological,
      biochemical, and hormonal data of patients at presentation.

PMID- 18078866
TI  - Reduced venous endothelial responsiveness after oral lipid overload in healthy
      volunteers.
AB  - The aim of this study was to investigate endothelial venous function,
      inflammatory markers, and systemic oxidative stress after an oral lipid overload
      (OLO). We studied 18 healthy adults (9 men; age, 29.2 +/- 0.9 years; body mass
      index, 22.3 +/- 0.4 kg/m(2)). Blood samples were collected in the fasting state
      and 3, 4, and 5 hour after the OLO (1000 kcal, 58% fat) for metabolic variables,
      oxidative stress, inflammatory markers, adiponectin, and resistin. Changes in
      vein diameter to phenylephrine, acetylcholine, and sodium nitroprusside (dorsal
      hand vein technique) were measured before and after the OLO. Oral lipid overload
      increased triglycerides (61 +/- 6 vs 134 +/- 17 mg/dL, P < .001), insulin (7.2 +/
      0.8 vs 10.7 +/- 1.3 muU/mL, P < .05), and resistin (5.38 +/- 0.5 vs 6.81 +/- 0.7
      ng/mL, P < .05) and reduced antioxidant capacity (plasma total antioxidant
      capacity: 186.7 +/- 56 vs 161.8 +/- 50 U Trolox per microliter plasma, P < .01),
      vascular reactivity (171.3 +/- 85 vs 894.4 +/- 301 ng/mL, P < .001), and maximum
      acetylcholine venodilation (105.9% +/- 9% vs 61.0% +/- 7%, P < .05). No changes
      were observed for sodium nitroprusside. Post-OLO triglycerides were positively
      correlated with phenylephrine dose (rho = 0.38, P < .05) and resistin (rho =
      0.43, P < .01) and negatively correlated with the maximum acetylcholine
      venodilation (rho = -0.36, P < .05). In conclusion, an OLO impaired
      venoconstriction responsiveness in healthy subjects, probably because of a
      reduction in the antioxidant capacity.

PMID- 18078867
TI  - The relationship between plasma asymmetrical dimethyl-L-arginine and inflammation
      and adhesion molecule levels in subjects with normal, impaired, and diabetic
      glucose tolerance.
AB  - Increasing evidence suggests that the postprandial state is a contributing factor
      to the development of atherosclerosis. To evaluate the effects of acute
      hyperglycemia on endothelial dysfunction and inflammation, plasma asymmetrical
      dimethyl-l-arginine (ADMA), intercellular adhesion molecule 1 (sICAM-1), vascular
      cell adhesion molecule 1, and C-reactive protein (CRP) levels and secretory
      phospholipase A(2) (sPLA(2)) activities were measured in subjects with normal (n
      = 35), impaired (IGT) (n = 25), and diabetic (DGT) (n = 20) glucose tolerance. At
      baseline, plasma ADMA, sICAM-1, and CRP concentrations and plasma sPLA(2)
      activities were higher in both the IGT and DGT groups than in the normal glucose
      tolerance group (for each comparison, each P < .001). Patients with DGT have
      higher plasma ADMA and sICAM-1 concentrations than patients with IGT (for each, P
      < .001).Two hours after glucose loading, plasma ADMA and CRP concentrations and
      sPLA(2) activities were significantly elevated in the 3 groups when compared with
      baseline levels (for each comparison, P < .001). Plasma vascular cell adhesion
      molecule 1 and sICAM-1 concentrations were found to be elevated from baseline
      levels after glucose loading in the IGT and DGT groups (for each comparison, P <
      .001). Correlation analysis at baseline suggested that there was a significant
      relationship between ADMA and inflammation and soluble adhesion markers in the
      studied groups. In conclusion, plasma concentrations of ADMA and of inflammation
      and adhesion molecules were elevated in the prediabetic state. A complex
      interrelation could exist between ADMA and inflammation, and mechanisms involved
      in endothelial dysfunction are multifactorial at the prediabetic and diabetic
      state.

PMID- 18078868
TI  - Evidence for strict inpatient blood glucose control: time to revise glycemic
      goals in hospitalized patients.
AB  - Inpatient hyperglycemia in patients with and without a history of diabetes is
      common and is associated with increased hospital morbidity and mortality. The
      objectives of this communication are to examine results of randomized clinical
      trials of strict inpatient glucose control in medical and surgical intensive care
      units and to provide guidelines for achieving and maintaining glycemic control in
      patients admitted to critical and noncritical settings. We propose a more
      conservative approach of glycemic control than current American Association of
      Clinical Endocrinology recommendations until results of prospective, multicenter,
      randomized studies become available.

PMID- 18078869
TI  - Impact of 5 years of growth hormone replacement therapy on cardiovascular risk
      factors in growth hormone-deficient adults.
AB  - The benefits of long-term effects of growth hormone (GH) substitution on
      carbohydrate and lipid metabolism in GH-deficient (GHD) adults are still
      controversial. The purpose of this study was to evaluate the effects of 5 years
      of GH substitution on body composition, glucose and lipid metabolism, and carotid
      artery intima-media thickness (IMT) in GHD adults. Fourteen patients were
      clinically assessed every 3 months for 5 years. Serum insulin-like growth factor
      1 levels, lipid profile, oral glucose tolerance test, and ultrasonography of the
      carotid arteries were performed at baseline, 6 months, and every year during
      replacement. Visceral fat was measured by computed tomographic scan at baseline
      and at 6, 12, 24, and 60 months. The waist circumference was reduced after 6
      months but increased during the next months toward baseline values. Visceral fat
      decreased during the study. Fasting glucose and insulin levels did not change, as
      well as the homeostasis model assessment of insulin resistance index. Despite an
      initial increase in frequency of abnormal glucose tolerance, mean 2-hour oral
      glucose tolerance test glucose levels decreased during the last 2 years. There
      was an increase in apolipoprotein A-1 levels during the treatment. Apolipoprotein
      B levels were reduced after 6 months and remained stable thereafter. A reduction
      in carotid artery IMT was observed during replacement. We concluded that 5 years
      of GH replacement therapy promoted positive effects on visceral fat, lipid
      profile, and carotid artery IMT in GHD adults. Long-term therapy improves insulin
      sensitivity through a reduction in visceral fat, and continuing monitoring is
      mandatory in terms of glucose metabolism.

PMID- 18078870
TI  - Effect of plant sterols in combination with other cholesterol-lowering foods.
AB  - The National Cholesterol Education Program Adult Treatment Panel III guidelines
      advocate effective combinations of cholesterol-lowering dietary components. This
      approach (dietary portfolio) produces large reductions in serum cholesterol, but
      the contribution of individual components remains to be established. We therefore
      assessed the effect of eliminating one out of the 4 dietary portfolio components.
      Plant sterols were selected because at 2 g/d, they have been reported to reduce
      low-density lipoprotein cholesterol (LDL-C) by 9% to 14%. Forty-two
      hyperlipidemic subjects were prescribed diets high in soy protein (22.5 g/1000
      kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal) for 80
      weeks. Subjects were instructed to take these together with plant sterols (1.0
      g/1000 kcal) except between weeks 52 and 62. While taking the full dietary
      portfolio, including plant sterols, mean LDL-C reduction from baseline was 15.4%
      +/- 1.6% (P < .001). After sterol elimination, mean LDL-C reduction was 9.0% +/-
      1.5% (P < .001). Comparable LDL-C reductions were also seen for the 18 subjects
      with a complete data set: on plant sterols, 16.7% +/- 3.1% (P < .001) and off
      plant sterols, 10.3% +/- 2.6% (P < .001), resulting in a 6.3% +/- 2.0% (P = .005)
      difference attributable to plant sterols. Compliance in this group of 18 was
      67.0% +/- 5.9% for plant sterols and 61.9% +/- 4.8% for the other components. In
      combination with other cholesterol-lowering foods and against the background of a
      low-saturated fat diet, plant sterols contributed over one third of the LDL-C
      reduction seen with the dietary portfolio after 1 year of following dietary
      advice.

PMID- 18078871
TI  - Nateglinide prevents fatty liver through up-regulation of lipid oxidation pathway
      in Goto-Kakizaki rats on a high-fat diet.
AB  - Dyslipidemia and fatty liver are important components of the metabolic syndrome
      and are the factors most commonly associated with the development of nonalcoholic
      fatty liver disease. Delayed and excessive insulin secretion in response to food
      intake is a key element in the onset of these risk factors. Nateglinide (NAT) is
      known to restore early-phase insulin secretion. We assessed the effect of NAT on
      postprandial hypertriglyceridemia and fatty liver in type 2 diabetic Goto
      Kakizaki (GK) rats. The GK rats fed a high-fat diet containing 30% beef tallow
      twice a day were administered either the vehicle alone or NAT (50 mg/kg) before
      each meal for 12 weeks. Delayed insulin secretion and an increase of total
      insulin release were caused by feeding 30% beef tallow to the rats. This diet
      also induced postprandial hypertriglyceridemia and increased the hepatic
      triglyceride content. Treatment with NAT restored early-phase insulin secretion
      without any increase of total insulin release and also reduced postprandial
      hypertriglyceridemia and the hepatic triglyceride content. There was up
      regulation of the hepatic expression of peroxisome proliferators-activated
      receptor alpha and its downstream enzymes after 12 weeks of NAT treatment, as
      well as normalization of the plasma total ketone body level. Furthermore, NAT
      also up-regulated hepatic expression of the adiponectin receptor AdipoR2,
      although there was no effect on the plasma adiponectin level. These findings
      indicate that long-term treatment with NAT prevented the development of fatty
      liver through the up-regulation of hepatic lipid oxidation pathways. Restoration
      of early-phase insulin secretion and suppression of recurrent postprandial
      hypertriglyceridemia might be involved in these effects of NAT. The present
      results may support the use of NAT to prevent the onset and progression of the
      metabolic syndrome and chronic liver disease.

PMID- 18078872
TI  - Modulation of the human equilibrative nucleoside transporter1 (hENT1) activity by
      IL-4 and PMA in B cells from chronic lymphocytic leukemia.
AB  - Nucleoside transporters (NTs) are essential for the uptake of therapeutic
      nucleoside analogs, broadly used in cancer treatment. The mechanisms responsible
      for NT regulation are largely unknown. IL-4 is a pro-survival signal for chronic
      lymphocytic leukemia (CLL) cells and has been shown to confer resistance to
      nucleoside analogs. The aim of this study was to investigate whether IL-4 is able
      to modulate the expression and function of the human equilibrative NT1 (hENT1) in
      primary cultures of CLL cells and, consequently, to affect cytotoxicity induced
      by therapeutic nucleosides analogs. We found that treatment with IL-4 (20 ng/ml
      for 24 h) increased mRNA hENT1 expression in CLL cells without affecting that of
      normal B cells. Given that the enhanced mRNA levels of hENT1 in CLL cells did not
      result in increased transport activity, we examined the possibility that hENT1
      induced by IL-4 may require post-translational modifications to become active. We
      found that the acute stimulation of PKC in IL-4-treated CLL cells by short-term
      incubation with PMA significantly increased hENT1 transport activity and favoured
      fludarabine-induced apoptosis. By contrast, and in line with previous reports, IL
      4 plus PMA protected CLL cells from a variety of cytotoxic agents. Our findings
      indicate that the combined treatment with IL-4 and PMA enhances hENT1 activity
      and specifically sensitizes CLL cells to undergo apoptosis induced by
      fludarabine.

PMID- 18078873
TI  - Long-term follow-up of a hydroxyapatite ceramic-coated threaded cup: an analysis
      of survival and fixation at up to 15 years.
AB  - We evaluated the survival of 112 consecutive JRI hydroxyapatite ceramic-coated
      threaded acetabular components (JRI Ltd, London, UK). Follow-up was for a minimum
      of 13 years (range, 13-15 years). Patients were assessed clinically and
      radiographically using the Merle d'Aubigne and Postel scoring systems and the De
      Lee and Charnley zones. Cup angle, migration, and signs of radiolucency were used
      to assess loosening. The criteria for failure were revision or impending revision
      due to pain and septic or aseptic loosening. The mean results of the Merle
      d'Aubigne and Postel score for pain, motion, and ability to walk were 2.2/2.7/2.2
      preoperatively and 5.6/4.3/5.1 postoperatively. There was 100% endosteal bone
      formation in De Lee and Charnley zones 1 and 3 and 87% in zone 2. No reactive
      lines were seen in any zone in any cup. There were no cases of migration, change
      in cup angle, or revision for loosening. Our survival was 99% at 13 years (95%
      confidence interval, 96-100).

PMID- 18078874
TI  - Acetabular revision with extensive allograft impaction and uncemented
      hydroxyapatite-coated implants. Results after 9 (7-11) years follow-up.
AB  - This is a clinical and radiographic review of 87 hips in 79 patients 9 (7-11)
      years after acetabular revision with extensive use of morselized allograft firmly
      impacted into localized defects as well as the entire acetabular cavity, followed
      by insertion of an uncemented hydroxyapatite-coated cup with supplementary screw
      fixation. The 9-year survival rate for the acetabular implant was 90.5% (95% CI,
      83.4%-97.6%) with revision for any reason as end point and 94% (95% CI, 89%
      99.1%) with revision for aseptic loosening as end point. Acetabular revision with
      massive allograft impaction and hydroxyapatite-coated implants show very
      promising results. The limited contact between implant and host bone does not
      seem to compromise implant survival in the 7- to 11-year perspective.

PMID- 18078875
TI  - The role of flexion contracture on outcomes in primary total knee arthroplasty.
AB  - This study examined the role that flexion contracture plays in postoperative
      outcomes after total knee arthroplasty using a retrospective database review. The
      relationships between preoperative and postoperative knee extension, walking
      ability, stair climbing ability, Knee Society scores, pain scores, and knee
      function scores were studied in 5,622 knees. A preoperative flexion contracture
      was associated with an increased incidence of a persistent postoperative flexion
      deformity. A postoperative flexion contracture was associated with poorer
      postoperative results. Furthermore, a postoperative hyperextension deformity of
      greater than 10 degrees was associated with an increased risk of suboptimal pain
      and Knee Society scores. Knee extension deformities play a substantial
      detrimental role in the functional outcome of primary total knee arthroplasty.

PMID- 18078876
TI  - Meta-analysis of alignment outcomes in computer-assisted total knee arthroplasty
      surgery.
AB  - Computer-assisted surgery (CAS) has been advocated as a means to improve limb and
      prosthesis alignment and assist in ligament balancing in total knee arthroplasty
      (TKA). Thus, we sought to examine alignment outcomes in CAS vs conventional TKA.
      A systematic review of literature from 1990 to 2007 was performed. Direct
      comparison of alignment outcomes was performed using random effects meta
      analyses. Twenty-nine studies of CAS vs conventional TKA were identified, and
      included mechanical axis malalignment of greater than 3 degrees occurred in 9.0%
      of CAS vs 31.8% of conventional TKA patients. The risk of greater than 3 degrees
      malalignment was significantly less with CAS than conventional techniques for
      mechanical axis and frontal plane femoral and tibial component alignment. Tibial
      and femoral slope both showed statistical significance in favor of CAS at greater
      than 2 degrees malalignment. Meta-analysis of alignment outcomes for CAS vs
      conventional TKA indicates significant improvement in component orientation and
      mechanical axis when CAS is used.

PMID- 18078877
TI  - Comparative study of stability after total knee arthroplasties between navigation
      system and conventional techniques.
AB  - The aim of this study was to evaluate the stability of mediolateral laxity in
      extension and anteroposterior laxity in 90 degrees of flexion using stress
      radiographs, modified Hospital for Special Surgery scores, and range of motion of
      total knee arthroplasties (TKAs) performed using a navigation system (navigation
      assisted group, 42 knees) after a minimum 1-year follow-up and to compare them
      with those of a conventional TKA (conventional group, 44 knees) using a gap
      technique. The mean medial laxities were 3.5 degrees in the navigation-assisted
      group and 4.0 degrees in the conventional group, and the mean lateral and
      anteroposterior laxities were 4.4 degrees and 4.2 degrees in 7.1 and 7.0 mm,
      respectively. These results showed no significant differences between the 2
      groups. Thus, we concluded that there is no significant difference between
      navigation-based and conventional techniques in terms of TKA stability. In
      addition, no significant differences were found between the 2 groups in modified
      HSS scores or range of motion.

PMID- 18078878
TI  - Hybrid total knee arthroplasty analysis of component failures at an average of 15
      years.
AB  - Hybrid total knee arthroplasty in which the femoral component is cementless and
      the tibial component is cemented remains controversial. We report on the long
      term results of 65 total knee arthroplasties followed for an average of 15 years.
      There were 18 revisions (27%); of these, 11 were femoral component revisions. The
      overall implant survival with revision as the end point was estimated as 64% at
      15 years. The femoral component survivorship at 15 years was 72%. Because of the
      high failure rate, hybrid fixation on the femoral side with this design has been
      abandoned at our institution; but hybrid fixation with a trabecular metal tibia
      is currently under investigation.

PMID- 18078879
TI  - Functional advantage of articulating versus static spacers in 2-stage revision
      for total knee arthroplasty infection.
AB  - Infection is an unfortunate complication of total knee arthroplasty. Current
      literature supports 2-stage reimplantation as the gold standard. Controversy
      exists whether static or articulating spacers are the best interim treatment
      method. Seventy-six 2-stage reimplantation procedures met the study inclusion
      criteria. There were 28 static spacers and 48 articulating spacers. The
      eradication rate was 94.7% in the articulating group compared with 92.1% in the
      static group (P = 0.7). There were no significant differences in postoperative
      Knee Society Scores pain scores. There were 28 (58%) good to excellent function
      scores in the articulating group and 10 (36%) in the static group (P = .05).
      Interim use of an articulating spacer maintains excellent infection eradication
      rates and may improve function over the use of static spacers.

PMID- 18078880
TI  - The effect of early weight bearing on migration pattern of the uncemented CLS
      stem in total hip arthroplasty.
AB  - Forty-two patients (younger than 65 years) with osteoarthritis were operated on
      with an uncemented CLS stem and randomized to early unrestricted weight bearing
      combined with intensive physiotherapy or to partial weight bearing combined with
      self-training. Radiostereometric analysis showed 1.2 (+0.11 to -6.76) mm
      subsidence of the stem at 24 months in both groups. There was no significant
      difference in the migration pattern between the unrestricted and partial weight
      bearing groups. Actual loading on the operated leg, measured with the F-scan
      system, did not influence the migration of the stem. There was a strong
      correlation between the average subsidence at 3 and 24 months (r = 0.96). Early
      full weight bearing and active rehabilitation can be used for the uncemented CLS
      stem without increased risk of early loosening.

PMID- 18078881
TI  - Ipsilateral patellofemoral arthroplasty and autogenous osteochondral femoral
      condylar transplantation.
AB  - The aim of this study was to report the results of ipsilateral patellofemoral
      arthroplasty and autologous osteochondral transplantation for patellofemoral
      arthritis and focal full-thickness chondral defects of the femoral condyles. The
      size of the condylar cartilage defects ranged from as small as 10 x 9 mm to as
      big as 24 x 7 mm. The mean Knee Society function score improved from 49 to 93,
      and the clinical score improved from 47 to 95. The mean patellofemoral pain score
      improved from 12 to 49, and the patellofemoral function score increased from 16
      to 42. There have been no radiographic signs of progressive tibiofemoral
      cartilage degeneration. Combining patellofemoral arthroplasty and autologous
      osteochondral transplantation is a reasonable short-term approach to this
      condition.

PMID- 18078882
TI  - The natural history of osteoarthritic bone cysts after uncemented total hip
      arthroplasty.
AB  - This study quantified the radiographic changes of osteoarthritic acetabular bone
      cysts after uncemented total hip arthroplasty (THA). Ten-year follow-up
      radiographs from 130 primary THAs were reviewed. Forty-one cysts were identified
      on immediate postoperative radiographs. Two-dimensional cyst size was measured
      postoperatively and on long-term radiographs. Mean initial cyst size was 1.0 +/-
      0.9 cm(2). Four (10%) of the 41 cysts expanded over time. The average increase in
      cyst size was 5.1 +/- 8.6 cm(2) which equated to a mean size increase of 713%.
      Twenty-seven cysts (66%) shrank, and the remaining 10 cysts (24%) did not change
      with time. Because cysts located in zone II, near the dome hole of the cup, were
      statistically more likely to progress, we hypothesize that these cysts
      communicated with the joint space via these holes. We propose that placing the
      acetabular component to seal an osteoarthritic cyst from the joint space during
      THA can help prevent its subsequent progression and the risk of associated
      osteolysis.

PMID- 18078883
TI  - Primary total hip arthroplasty in protrusio acetabuli using impacted morsellized
      bone grafting and cementless cups: a medium-term radiographic review.
AB  - Thirty primary total hip arthroplasties were performed for protrusio acetabuli in
      23 patients (mean age, 46 years) using impacted autologous bone grafting and a
      cementless porous-coated hemispheric cup without the use of metal cages or rings.
      At 2 to 10 years' follow-up (mean, 4.2 years), there was satisfactory
      radiographic evidence of consolidation of the graft in all cases. All acetabular
      components were considered to be stable with no instance of graft resorption.
      Clinical results were considered as excellent in 14 hips, good in 13 hips, fair
      in 2 hips, and poor in 1 hip. For younger patients with protrusio acetabuli, use
      of an uncemented porous-coated hemispheric cup with peripheral press-fit fixation
      and restoration of bone stock with impacted autologous bone grafting reflect a
      technically straightforward procedure that appears to give satisfactory medium
      term results.

PMID- 18078884
TI  - Interobserver and intra-observer errors in obtaining visually selected anatomical
      landmarks during registration process in non-image-based navigation-assisted
      total knee arthroplasty.
AB  - This study investigated the errors of obtaining visually selected anatomic
      landmarks for use in the registration process in a passive optical non-image
      based computer-assisted total knee arthroplasty system in 5 fresh frozen
      cadavers. The projected maximum errors in the femoral mechanical axis (due to
      registration errors of the center of the distal femur) were 0.7 degrees in the
      coronal and 1.4 degrees in the sagittal plane. The projected maximum errors in
      the tibial mechanical axis arising from registration errors of the center of the
      proximal tibia were 1.3 degrees in the coronal and 2 degrees in the sagittal
      plane. The projected maximum errors in the transepicondylar axis were 9.1 degrees
      (registration errors of the medial femoral epicondyle) and 7.2 degrees
      (registration errors of the lateral femoral epicondyle). It should be noted that
      the results may be partly related to the use of the particular system in this
      experiment.

PMID- 18078885
TI  - Relative risk factors for requirement of blood transfusion after total hip
      arthroplasty.
AB  - One thousand thirty-five total hip arthroplasty (THA) cases were retrospectively
      reviewed, and the number and type (autologous and allogenic) of postoperative
      units of blood transfused were analyzed with respect to pre-, intra-, and
      postoperative variables. The most significant and consistent predictors of a
      blood transfusion after THA were advanced age and the use of low-molecular-weight
      heparin for deep venous thrombosis prophylaxis. Our recommendations for
      predonation are 1 unit for THA patients younger than 75 years if hemoglobin is
      130 g/dL or greater and 2 units or a combination of 1 unit of predonated blood
      and 1 unit of directed or banked blood for THA patients older than 75 years.

PMID- 18078886
TI  - Comparison of the responsiveness of the SF-36 and WOMAC in patients undergoing
      total hip arthroplasty.
AB  - This study examines the responsiveness of the Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) and Short Form-36 (SF-36) in patients
      undergoing total hip arthroplasty. Eighty-nine patients completed the WOMAC and
      SF-36 preoperatively and postoperatively. Standardized response means (SRMs) and
      effect sizes (ES) were used to measure responsiveness. Mean follow-up was 17
      months. The SRMs for the WOMAC ranged from -0.93 to -1.49, and the ES ranged from
      -1.02 to -1.53. The SRMs for the SF-36 ranged from 0.22 to 1.64, and the ES
      ranged from 0.20 to 1.97. The highest values occurred with the physical
      functioning, bodily pain, and Physical Component Summary Scales. This study
      demonstrates a similar level of responsiveness of the WOMAC and several
      components of the SF-36. This suggests that the isolated use of the SF-36 may be
      adequate to monitor outcomes after total hip arthroplasty. There may still be a
      role for the WOMAC when comparing outcomes of specific designs or techniques of
      total hip arthroplasty.

PMID- 18078887
TI  - Use of oxidized zirconium hemiarthroplasty in hip fractures: clinical results and
      spectrum analysis.
AB  - Oxidized zirconium may have improved wear characteristics against polyethylene,
      but its performance against native cartilage is unknown. Between 1996 and 1998,
      52 patients received an oxidized zirconium hemiarthroplasty for the treatment of
      a hip fracture. Twelve patients (23%) died within 1 year of surgery, and 24 (46%)
      were surviving at 5 years. In 38 patients with minimum 2-years follow-up,
      clinical evaluation after surgery averaged 4.5 years with Harris hip scores
      averaging 78 (range, 55-92). Three patients radiographically showed acetabular
      protrusion or significant wear, with 2 undergoing revision surgery. An explanted
      prosthesis demonstrated no appreciable damage by spectrum analysis. Because of
      the high mortality rate after hip fracture, the clinical benefits of oxidized
      zirconium hemiarthroplasty in this population, if existent, are difficult to
      appreciate and currently show no benefits over standard prostheses.

PMID- 18078888
TI  - Combined continuous "3-in-1" and sciatic nerve blocks provide improved
      postoperative analgesia with no correlation to catheter tip location after
      unilateral total knee arthroplasty.
AB  - This study assessed the efficacy and duration of postoperative analgesia after
      continuous sciatic nerve block with and without continuous "3-in-1" block with
      bupivacaine after unilateral total knee arthroplasty and determined catheter tip
      correlation with analgesia. Thirty patients were randomized into 2 groups.
      Results suggested significantly reduced pain and rescue analgesic requirement in
      combined sciatic and 3-in-1 (group TS) compared to 3-in-1 group alone (group T).
      The postoperative pain-free interval and satisfaction score was significantly
      higher in the combined group (P < .05). The percentage of catheters in the ideal
      position was 53.3% for 3-in-1 and 93.3% for sciatic nerve. In conclusion,
      continuous sciatic nerve block when added to continuous 3-in-1 block provides a
      better quality of analgesia with lesser requirements of rescue analgesics without
      the need for routine radiographic conformation.

PMID- 18078889
TI  - Effects of anterolateral minimally invasive surgery in total hip arthroplasty on
      hip muscle strength, walking speed, and functional score.
AB  - We conducted this study to observe the difference in muscle strength and walking
      speed between patients who underwent total hip arthroplasty (THA) in whom an
      anterolateral mini-incision technique was used and those in whom a conventional
      approach was used. Fifty-three patients who underwent a mini-incision THA were
      matched by diagnosis, sex, age, period elapsed since surgery (which ranged from 6
      months to 4 years), weight, and height to 53 patients who underwent THA using the
      conventional anterolateral approach. During the first year after surgery,
      patients with the mini-incision THA had significantly better hip muscle strength,
      walking speed, and functional score (P < .05). At 1 year, the performance
      characteristics studied were statistically equivalent (P > .05). Although the
      mini-incision technique is more difficult than the conventional technique, its
      use by experienced surgeons can produce quicker short-term recovery.

PMID- 18078890
TI  - Noise exposure due to orthopedic saws in simulated total knee arthroplasty
      surgery.
AB  - In some orthopedic procedures, including total knee arthroplasty (TKA), surgeons
      are exposed to noise generated by powered instruments, with a risk of developing
      occupational hearing loss. A new saw design, the Stryker Precision system
      (Stryker, Kalamazoo, Mich), has been developed that may reduce noise during TKA
      surgery. The new system was tested against a standard Stryker System 5 sagittal
      saw in simulated TKA surgery using porcine cadaveric femurs, and noise levels
      from the cuts were measured. The average noise level of the Precision system,
      L(Aeq) = 81.6 dB(A), was significantly lower than that of the System 5 saw,
      L(Aeq) = 88.9 dB(A) (P = .003). Calculated 8-hour values for both blade systems
      were within Health and Safety guidelines. It was concluded that the Precision
      system produced a lower risk of noise-induced hearing loss than the System 5 saw.

PMID- 18078891
TI  - Damage to the superior gluteal nerve during the direct lateral approach to the
      hip: a cadaveric study.
AB  - The direct lateral approach to the hip is one of the most commonly used surgical
      approaches for hip arthroplasty. The inferior division of the superior gluteal
      nerve (SGN) is the main nerve supply to the abductor muscles of the hip and may
      be damaged during this approach. The exact incidence of permanent damage to the
      SGN is not known. The present study is based on cadaveric dissection of the SGN
      after a surgical approach to the hip joint for hip arthroplasty. The inferior
      division of the SGN was found to be damaged in 3 (6.8%) of 44 cases. We conclude
      that a true "safe zone" does not exist when using a direct lateral approach. We
      also found out that the incidence of physical damage to the SGN is rare and
      depends largely on the branching pattern of the nerve.

PMID- 18078892
TI  - The position of the joint line in relation to the trans-epicondylar axis of the
      knee: complementary radiologic and computer-based studies.
AB  - Two complementary studies that seek to establish the relationship between the
      length and position of the trans-epicondylar axis (TEAL) of the distal femur and
      the position of the knee joint line were presented. A radiologic study of 50
      patients having computerized axial tomography of the knee showed that there is a
      good correlation between TEAL and the depths of the femoral condyles distal to
      the trans-epicondylar axis. A retrospective review of the anatomical data
      gathered on 99 patients having computer-assisted total knee arthroplasties (TKAs)
      provided equivalent information. The 2 studies suggest that TEAL determined by
      the process of registration, as a preliminary to computer-assisted TKA, can be
      used to predict the position of the joint line using the derived constant k at a
      value of 3.4. Thus, the joint line of the knee lies at a distance (TEAL / 3.4)
      expressed in millimeters from the trans-epicondylar axis. This is potentially
      very useful information during TKA especially where there is extensive femoral
      bone loss.

PMID- 18078893
TI  - Proximal femoral bone mineral density after resurfacing total hip arthroplasty
      and after standard stem-type cementless total hip arthroplasty, both having
      similar neck preservation and the same articulation type.
AB  - To examine whether the Freeman cementless total hip arthroplasty (THA), with
      femoral neck preservation and a large metal head, can prevent stress shielding in
      a manner similar to resurfacing THA, we compared femoral bone mineral density
      (BMD) change in 10 resurfacing THA patients (group A) and 16 cementless THA
      patients (group B). Six and twelve months postoperatively, the mean BMD ratio in
      zone 1 was significantly higher in group A (97% +/- 10%, 95% +/- 11%) than in
      group B (79% +/- 15%, 77% +/- 20%); at 12 months, the mean BMD ratio in zone 7
      was significantly higher in group A (104% +/- 15%) than in group B (84% +/- 21%).
      The cementless THA might not be a substitute for the resurfacing THA with respect
      to prevention of proximal femoral bone loss at the femoral neck, although it may
      prevent some major complications after resurfacing THA such as neck fracture and
      avascular necrosis of the femoral head.

PMID- 18078894
TI  - Revision total knee arthroplasty for excessive ligamentotaxis.
AB  - Correction of varus/valgus deformity via soft tissue balancing is the accepted
      technique in knee arthroplasty surgery. However, in rare instances, excessive
      ligamentotaxis can result in overly stretched periarticular structures leading to
      pain and impaired function. This has been called the "joint jack phenomenon." We
      report a case in which a very thick polyethylene insert resulted in a painful
      knee and leg length discrepancy. Our solution was to use a salvage hinge knee
      arthroplasty to achieve joint space reduction, restore equal leg lengths, and
      avoid global instability. We believe this is the first report of a surgical
      reduction procedure to address this specific clinical problem.

PMID- 18078895
TI  - Lining up the liner: 2 case reports of early ceramic liner fragmentation.
AB  - We present 2 cases of early ceramic liner fragmentation in patients undergoing
      ceramic-on-ceramic uncemented total hip arthroplasty. The reports highlight the
      significance of correct liner insertion at the time of operation and the
      importance of a meticulous evaluation of postoperative radiographs. Tilting of
      the liner may not be visualized on the anteroposterior roentgenogram alone.
      Preradiological ceramic fragmentation can occur.

PMID- 18078896
TI  - Therapeutic embolization for the treatment of recurrent hemarthrosis after total
      knee arthroplasty due to an arteriovenous fistula.
AB  - We describe the case of a 79-year-old woman who presented with recurrent
      hemarthrosis 8 years after primary total knee arthroplasty. An arteriovenous
      fistula of the superior lateral geniculate artery was diagnosed by arteriography
      after arthroscopy of the knee revealed multiple organized hematomata with minimal
      synovitis. The arteriovenous fistula was treated by percutaneous coil
      embolization and the symptoms resolved.

PMID- 18078897
TI  - Hypersensitivity to benzoyl peroxide in a cemented total knee arthroplasty:
      cement allergy.
AB  - A small but significant proportion of cemented total knee arthroplasties develop
      aseptic loosening. Polyethylene debris is unlikely to be the cause in the small
      subgroup that experiences early loosening. Allergy to polymethylmethacrylate bone
      cement or its constituents has been reported in several different industries and
      in dentistry, dermatology, and joint arthroplasty. Although allergy to
      polymethylmethacrylate bone cement or its constituents is unusual, the
      possibility of a systemic inflammatory response and consequent pain and loosening
      must be considered. We report a case history of a patient who developed a
      systemic reaction and intractable pain after a total knee arthroplasty who was
      subsequently shown to be hypersensitive to the benzoyl peroxide component of bone
      cement.

PMID- 18078898
TI  - An unusual case of pigmented villonodular synovitis after total knee
      arthroplasty.
AB  - We describe a case of focal pigmented villonodular synovitis in the knee
      presenting 12 months after total knee arthroplasty. The abnormal synovial
      proliferation was noted at arthroscopy, and histological analysis of the resected
      tissue confirmed the diagnosis.

PMID- 18078899
TI  - Postoperative wound breakdown caused by pyoderma gangrenosum after bilateral
      simultaneous total knee arthroplasty.
AB  - Pyoderma gangrenosum is a noninfective necrosis of dermal tissues. Rarely, it
      occurs after surgery or trauma. However, lack of awareness and its striking
      similarity to a clinical picture of sepsis usually delay diagnosis and initiation
      of the correct management. We describe a unique case of its occurrence in both
      surgical wounds after bilateral total knee arthroplasty and discuss the
      differential diagnoses and management.

PMID- 18078900
TI  - Is a change as good with a rest? Task-dependent effects of inter-trial
      contingency on concurrent sound segregation.
AB  - The effects of local and global context on concurrent sound segregation were
      examined using a mistuned harmonic paradigm. Presented with the same sounds over
      three conditions, participants were asked to either categorise the incoming
      complex according to pitch or harmonicity (active listening) or watch a muted
      subtitled movie of their choice (passive listening). Global context was defined
      according to task instruction, while local context was defined relative to the
      repetition or change of harmonicity across trials. An interaction between global
      and local context in both behavioural and event-related potential measures was
      found, with participants showing sensitivity to change and repetition in
      harmonicity when it was task-relevant, in addition to enhanced P3 amplitude for
      cases where a tuned stimulus changed into a mistuned stimulus over consecutive
      trials. The data are discussed in terms of current models of concurrent sound
      perception and how top-down processes might influence these mechanisms.

PMID- 18078901
TI  - Diagnosis of pulmonary embolism remains a challenge.

PMID- 18078902
TI  - Pretest risk assessment in suspected acute pulmonary embolism.
AB  - RATIONALE AND OBJECTIVES: To assess the pretest practices of US clinicians who
      treat patients with acute pulmonary embolism (PE). MATERIALS AND METHODS: We
      surveyed 855 practicing physicians selected randomly from three professional
      organizations. We asked participants to estimate how often and by what method
      they determine the likelihood of PE before they request confirmatory studies.
      Participants reported their awareness of four published clinical practice
      guidelines dealing with acute PE and selected options for further diagnostic
      testing after reviewing clinical data from three hypothetical patients presenting
      with low, intermediate, and high probability of acute PE. RESULTS: We received
      completed surveys from 240 physicians practicing in 44 states. Although most
      (98.3%) report that they assess pretest probability of PE before testing,
      slightly more than half do so routinely. A total of 72.5% prefer an unstructured
      approach to pretest assessment, whereas 22.9% use published prediction rules.
      Most (93.0%) are aware of at least one published guideline for assessing acute
      PE, but only 44.2% report using one or more in daily practice. Respondents who
      use published prediction rules, estimate pretest probability routinely, or use at
      least one practice guideline were more likely to request additional testing when
      reviewing a low probability clinical scenario. No differences in testing
      frequency or preferences were observed for intermediate or high probability
      clinical scenarios. CONCLUSIONS: The majority of clinicians we surveyed use an
      unstructured approach when estimating the pretest probability of acute PE. With
      the exception of low probability scenario, clinicians agreed on testing choices
      in suspected acute PE, regardless of the method or frequency of pre-test
      assessment.

PMID- 18078903
TI  - Diagnostic value of contrast-enhanced fluid-attenuated inversion-recovery and
      delayed contrast-enhanced brain MRI in multiple sclerosis.
AB  - RATIONALE AND OBJECTIVES: In brain MRI of multiple sclerosis (MS) patients,
      enhancement of the lesions is usually evaluated in early contrast-enhanced T1
      weighted images (CE-T1WI). The objective of this study is to determine the
      sensitivity of contrast-enhanced fluid-attenuated-inversion-recovery (CE-FLAIR)
      and delayed contrast-enhanced MRI in evaluation of MS brain lesions. MATERIALS
      AND METHODS: Brain MRI examination including early and delayed CE-T1WI and early
      and delayed CE-FLAIR images was performed for 46 patients with clinically
      definite MS disease. Number, size, location, degree, and pattern of enhancement
      of the enhanced lesions in each sequence were recorded separately. RESULTS: A
      total number of 87 enhanced lesions was detected in 30 patients. Early CE-T1WI
      could detect only 63 lesions (72.4% of total) in 24 patients, while delayed CE
      T1WI and early and delayed CE-FLAIR images showed 85 (97.7%), 84 (96.6%), and 81
      (93.1%) lesions in 28, 28, and 26 patients, respectively. A greater degree of
      enhancement and larger lesion size were observed in the additional sequences
      compared with the early CE-T1WI. CONCLUSIONS: The sensitivity of early CE-T1WI
      for the detection of enhanced MS lesions is significantly lower than that for
      other additional sequences. Delayed CE-FLAIR images could not add significant
      information to other sequences. Therefore, early CE-FLAIR and delayed CE-T1WI
      brain MRI can be considered as part of the evaluation of MS patients, especially
      if, despite clinically suspected active disease, no enhanced lesion is found in
      the routine CE-T1WI.

PMID- 18078904
TI  - Automatic and rapid identification of infarct slices and hemisphere in DWI scans.
AB  - RATIONALE AND OBJECTIVES: Accurate, free of observer's bias, and fast
      identification of acute infarct is critical in visual and automatic processing of
      stroke images. An automatic and rapid algorithm has been developed to identify
      the infarct slices and the hemisphere in diffusion-weighted imaging (DWI) scans.
      MATERIALS AND METHODS: Thirty-six DWI scans were acquired from five centers with
      the slice thickness of 4-14 mm. We also derive images from the original scans to
      assess the accuracy of the algorithm by using a wide range of infarct size and
      number of artifacts per unit area. Based on the difference in percentile
      characteristics of intensity normalized (infarct/noninfarct) images, two
      parameters are defined: R(s) for infarct slice identification and R(h) for
      infarct hemisphere identification. Using the identified infarct slices the
      infarct hemisphere is subsequently determined. RESULTS: The average sensitivity
      and specificity for slice and hemisphere identification were 98.1%, 51.4% and
      91.7%, 91.7%, respectively. The processing time is approximately 3-5 seconds on
      Matlab platform and on VC++ it is predicted approximately 10 milliseconds. Based
      on simulation study, we can infer that the algorithm produces accurate results in
      most of the situations although the sensitivity goes down by approximately 15%
      when the infarct size is small (<2-3% of image area) and the artifacts per unit
      area are large. CONCLUSIONS: The proposed algorithm applied as a preprocessor can
      be useful to: 1) estimate location (hemisphere) and extent of infarct (number and
      location of slices), 2) reduce time and labor of infarct volume study, 3) cross
      check visual interpretation, 4) form a part of an infarct segmentation module,
      and 5) improve localization of the midsagittal plane.

PMID- 18078905
TI  - Analysis of heart rate and heart rate variation during cardiac CT examinations.
AB  - RATIONALE AND OBJECTIVES: We sought to examine heart rate and heart rate
      variability during cardiac computed tomography (CT). MATERIALS AND METHODS:
      Ninety patients (59.0 +/- 13.5 years) underwent coronary CT angiography (CTA),
      with 52 patients also undergoing coronary artery calcium scanning (CAC). Forty
      two patients with heart rate greater than 70 bpm were pretreated with oral beta
      blockers (in five patients, use of beta-blocker was not known). Sixty-four
      patients were given sublingual nitroglycerin. Mean heart rate and percentage of
      beats outside a +/-5 bpm region about the mean were compared between baseline
      (free breathing), prescan hyperventilation, and scan acquisition (breath-hold).
      RESULTS: Mean scan acquisition time was 13.1 +/- 1.5 seconds for CAC scanning and
      14.2 +/- 2.9 seconds for coronary CTA. Mean heart rate during scan acquisition
      was significantly lower than at baseline (CAC 58.2 +/- 8.5 bpm; CTA 59.2 +/- 8.8
      bpm; baseline 62.8 +/- 8.9 bpm; P < .001). The percentage of beats outside a +/-5
      bpm about the mean were not different between baseline and CTA scanning (3.5%
      versus 3.3%, P = .87). The injection of contrast had no significant effect on
      heart rate (58.2 bpm versus 59.2 bpm, P = .24) or percentage of beats outside a
      +/-5 bpm about the mean (3.0% versus 3.3%, P = .64). No significant difference
      was found between gender and age groups (P > .05). CONCLUSIONS: Breath-holding
      during cardiac CT scan acquisition significantly lowers the mean heart rate by
      approximately 4 bpm, but heart rate variability is the same or less compared with
      normal breathing.

PMID- 18078906
TI  - Optimization of cardiac MSCT contrast injection protocols: dependency of the main
      bolus contrast density on test bolus parameters and patients' body weight.
AB  - RATIONALE AND OBJECTIVES: Our aim was to evaluate the correlation of test bolus
      (TB) curve parameters with main bolus (MB) contrast density for cardiac 16-slice
      computed tomography, and to correlate observed enhancement with patient body
      weight. MATERIALS AND METHODS: Sixty patients with known or suspected coronary
      artery disease were included in a prospective double-blind study. Contrast
      material containing 300 mg iodine/mL (Iomeprol 300; Imeron 300, Bracco Imaging
      SpA, Milan, Italy) and 400 mg iodine/mL (Iomeprol 400; Imeron 400) was injected
      at a rate of 1 g of iodine/second. Contrast densities (Hounsfield units) of the
      MB were determined in the left cardiac system. The peak density (PD) of maximum
      attenuation and the area under the curve (AUC) of the TB curve were calculated
      for each patient. The dependency of MB contrast attenuation on these parameters
      and on patient body weight was evaluated. RESULTS: Positive correlations (r =
      0.52 and r = 0.56, respectively; P < .0001) were obtained between the PD and AUC
      of the TB curve with the mean density of the MB. Stronger correlations (r = 0.63
      and r = 0.64, respectively; P < .0001) between PD and AUC of the TB curve and MB
      attenuation were found when patient body weight was included in the analysis.
      CONCLUSIONS: Strong correlation of the PD and AUC of the TB curve with the mean
      density of the MB is observed when patient body weight is considered. Contrast
      injection protocols may be optimized, and variations of MB contrast density in
      the left ventricle and main coronary arteries reduced, by taking these TB
      parameters and the weight of the patient into account.

PMID- 18078907
TI  - The interscan variation of CT coronary artery calcification score: analysis of
      the Calcium Acetate Renagel Comparison (CARE)-2 study.
AB  - RATIONALE AND OBJECTIVES: In the Calcium Acetate Renagel Evaluation (CARE)-2
      study, the effects of calcium acetate plus atorvastatin (Lipitor) on the
      progression of coronary artery calcifications (CACs) are evaluated versus those
      of Renagel, monitored using dual electron beam tomography (EBT) scans (two scans
      at study initiation and two at follow up). The aim of this study is to estimate
      the interscan variation for the Agatston score and for the volume score
      determined in patients with end-stage renal disease (ESRD) in the CARE-2 study.
      MATERIALS AND METHODS: CAC score and volume were measured at study initiation in
      463 ESRD subjects (mean age: 59.4 +/- 12.5 years, 48.3% female). All patients
      underwent dual scanning using an EBT, as first scan of two needed to measure the
      progression of CAC when treated with sevelamer (Renagel) compared with calcium
      acetate with or without atorvastatin. All scans in all participants were
      completed by using an EBT system (GE Imatron, South San Francisco, CA). Interscan
      variability was defined by the following formula: abs (scan A - scan B) / (0.5 x
      scan A + 0.5 x scan B) x 100%, where A and B denote the first and second scan,
      respectively, of the dual scan procedure performed before treatment. We evaluated
      the reproducibility of the cutpoints commonly used for calcium scores clinically,
      namely 1-30, 31-100, 101-400, and >400. RESULTS: The CAC interscan variability
      was 11.8% using the Agatston score and 10.3% using the volume score. The
      reproducibility was then assessed using cutpoints 1-30, 31-100, 101-400, and
      >400. Agatston score variability for the four subgroups was 61.3%, 23%, 16.1%,
      and 8.2%, respectively (mean variability, 11.8%). Volume score variability was
      60.0%, 14.4%, 14.6%, and 7.7%, respectively (mean variability, 10.3%). The
      correlation coefficient for scan A to scan B goes up significantly with
      increasing calcium scores and reaches 0.99 for scores greater than 400 (P <
      .0001). CONCLUSION: Interscan variability was sufficiently small for patients
      with calcium scores greater than 30. Our study thus demonstrates a sufficient
      reproducibility of the calcium score using EBT. This score allows for accurate
      serial assessment of these patients and for comparing different therapies.

PMID- 18078908
TI  - Comparison of low-dose CT and MR for measurement of intra-abdominal adipose
      tissue: a phantom and human study.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to determine the accuracy and
      reproducibility of low-dose computed tomography (CT) and magnetic resonance (MR)
      for abdominal adipose tissue quantification on phantom and human studies.
      MATERIALS AND METHODS: An adiposity phantom (with known internal/external oil
      volumes) was scanned at three different tube voltages (140, 120, and 90 kVp)
      using a 16-detector row CT scanner and was imaged using a T1-weighted spin echo
      MR sequence. For human studies, whole-volume coverage of the abdomen was obtained
      using CT (at 140 and 90 kVp) and T1-weighted spin echo MR imaging from five obese
      male volunteers (mean age, 40.6 years; mean body mass index, 30.2). The volumes
      of total, visceral, and subcutaneous adipose tissues (TAT, VAT, and SAT,
      respectively) were calculated independently by two radiologists for each CT scan
      and MR imaging using a computer-aided semiautomatic program. RESULTS: The
      estimated radiation dose could be reduced by approximately 75% with a 90-kVp
      protocol as compared with the 140-kVp protocol. Phantom studies showed that there
      was no statistically significant difference between the four methods in
      estimating the percentage predicted of the true volumes (measurement errors <4%
      for all methods, P > .05). In human studies, we found no statistically
      significant difference between the three methods in TAT, VAT, and SAT volumes (P
      > .05). Inter- and intraobserver reproducibilities of the CT volume estimates
      using the 90-kVp protocol were better than those obtained from MR imaging (kappa
      > 0.9 versus 0.4-0.5; coefficient of variation < 1% versus 15-22%). CONCLUSION:
      Low-dose CT provides accurate and reproducible measurement of abdominal adipose
      tissue volumes with a relevant dose reduction.

PMID- 18078909
TI  - Comparison of on-call radiology resident and faculty interpretation of 4- and 16
      row multidetector CT pulmonary angiography with indirect CT venography.
AB  - RATIONALE AND OBJECTIVES: On-call radiology residents frequently interpret
      computed tomography (CT) pulmonary angiography and CT venography studies outside
      of routine working hours. The purpose of this study was to compare resident and
      faculty interpretation concordance rates and to see if concordance rates differed
      depending on the number of CT detectors used. MATERIALS AND METHODS: The study
      population included 122 consecutive CT pulmonary angiography (CTPA) and CT
      venography (CTV) examinations performed on a four-row multidetector CT (MDCT) and
      125 consecutive CTPA examinations performed using a 16-row MDCT scanner with CTV
      performed in 124 patients. Preliminary resident reports and final faculty reports
      were compared. Discrepant cases were independently reviewed by three
      cardiothoracic radiologists who were unaware of the initial interpretations.
      Interpretation concordance rates were calculated for both 4- and 16- row MDCT
      studies and compared using Fisher's exact test. RESULTS: Resident and faculty
      CTPA and CTV interpretations were concordant in 80% of the 4-row cases and 94% of
      the 16-row cases. When comparing resident interpretation to the final expert
      reference standard, the corrected resident error rate was 11% and 2% for 4-row
      CTPA and CTV, respectively and 4% and 2% for 16-row CTPA and CTV, respectively.
      Overall CTPA and CTV concordance was significantly lower for 4-row MDCT (80%
      versus 94%, P < .001 [two-sided] by Fisher's exact test). CONCLUSIONS: Radiology
      resident interpretation of CTPA and CTV studies demonstrates a high level of
      agreement with radiology faculty interpretation. Concordance rates are
      significantly higher for 16-row MDCT than 4-row MDCT which may be due to improved
      image quality.

PMID- 18078910
TI  - Automatic prediction of infarct growth in acute ischemic stroke from MR apparent
      diffusion coefficient maps.
AB  - RATIONALE AND OBJECTIVES: We introduce a new approach to the prediction of final
      infarct growth in human acute ischemic stroke based on image analysis of the
      apparent diffusion coefficient (ADC) maps obtained from magnetic resonance
      imaging. Evidence from multiple previous studies indicate that ADC maps are
      likely to reveal brain regions belonging to the ischemic penumbra, that is, areas
      that may be at risk of infarction in the few hours following stroke onset.
      MATERIALS AND METHODS: In a context where "time is brain," and contrarily to the
      alternative-and still-debated-perfusion-diffusion weighted image (PWI/DWI)
      mismatch approach, the DWI magnetic resonance sequences are standardized, fast to
      acquire, and do not necessitate injection of a contrast agent. The image analysis
      approach presented here consists of the segmentation of the ischemic penumbra
      using a fast three-dimensional region-growing technique that mimics the growth of
      the infarct lesion during acute stroke. RESULTS: The method was evaluated with
      both numerical simulations and on two groups of 20 ischemic stroke patients (40
      patients total). The first group of patient data was used to adjust the
      parameters of the model ruling the region-growing procedure. The second group of
      patient data was dedicated to evaluation purposes only, with no subsequent
      adjustment of the free parameters of the image-analysis procedure. Results
      indicate that the predicted final infarct volumes are significantly correlated
      with the true final lesion volumes as revealed by follow-up measurements from DWI
      sequences. CONCLUSION: The DWI-ADC mismatch method is an encouraging fast
      alternative to the PWI-DWI mismatch approach to evaluate the likeliness of
      infarct growth during the acute stage of ischemic stroke.

PMID- 18078911
TI  - Quantitative diffusion tensor analysis using multiple tensor ellipsoids model and
      tensor field interpolation at fiber crossing.
AB  - RATIONALE AND OBJECTIVES: In regions of intravoxel fiber crossing, the single
      tensor model does not provide accurate results. The previously published models
      could resolve this issue but needed a long scan time and long computational time.
      This article aims to present the new model, which uses interpolated diffusion
      tensor orientations and requires the estimation of fewer parameters than the
      previously published model, where all parameters for the two diffusion ellipsoids
      have to be estimated. MATERIALS AND METHODS: Fiber orientation information was
      reconstructed by using the radial basis function-based interpolation technique
      from tensor information in given seed regions of interest. Synthetic phantom data
      were generated, and the proposed method was compared with the conventional two
      ellipsoid method. Data from one normal volunteer were analyzed to determine the
      effectiveness of the proposed method. The number of parameters to be estimated
      could be reduced by using the estimated fiber orientation information so that
      diffusion parameter calculation at fiber crossing becomes robust. RESULTS: The
      human study showed that fractional anisotropy (FA) values estimated by the
      proposed method (FA = 0.67 for the corpus callosum, 0.65 for the corticospinal
      tract) were significantly higher than that estimated by the standard single
      tensor-based method (FA = 0.35), and the estimated FA value showed good agreement
      with the FA value in the adjacent fiber bundle. CONCLUSION: The proposed radial
      basis function-based technique could reconstruct diffusion properties at the
      fiber-crossing volume from sparse sampling of high angular diffusion weighted
      images.

PMID- 18078912
TI  - Temporally targeted imaging method applied to ECG-gated computed tomography:
      preliminary phantom and in vivo experience.
AB  - RATIONALE AND OBJECTIVES: Existing cardiac imaging methods do not allow for
      improved temporal resolution when considering a targeted region of interest
      (ROI). The imaging method presented here enables improved temporal resolution for
      ROI imaging (namely, a reconstruction volume smaller than the complete field of
      view). Clinically, temporally targeted reconstruction would not change the
      primary means of reconstructing and evaluating images, but rather would enable
      the adjunct technique of ROI imaging, with improved temporal resolution compared
      with standard reconstruction ( approximately 20% smaller temporal scan window).
      In gated cardiac computed tomography (CT) scans improved temporal resolution
      directly translates into a reduction in motion artifacts for rapidly moving
      objects such as the coronary arteries. MATERIALS AND METHODS: Retrospectively
      electrocardiogram gated coronary angiography data from a 64-slice CT system were
      used. A motion phantom simulating the motion profile of a coronary artery was
      constructed and scanned. Additionally, an in vivo study was performed using a
      porcine model. Comparisons between the new reconstruction technique and the
      standard reconstruction are given for an ROI centered on the right coronary
      artery, and a pulmonary ROI. RESULTS: In both a well-controlled motion model and
      a porcine model results show a decrease in motion induced artifacts including
      motion blur and streak artifacts from contrast enhanced vessels within the
      targeted ROIs, as assessed through both qualitative and quantitative
      observations. CONCLUSION: Temporally targeted reconstruction techniques
      demonstrate the potential to reduce motion artifacts in coronary CT. Further
      study is warranted to demonstrate the conditions under which this technique will
      offer direct clinical utility. Improvement in temporal resolution for gated
      cardiac scans has implications for improving: contrast enhanced CT angiography,
      calcium scoring, and assessment of the pulmonary anatomy.

PMID- 18078913
TI  - Hypericin as a marker for determination of tissue viability after intratumoral
      ethanol injection in a murine liver tumor model.
AB  - RATIONALE AND OBJECTIVES: In this preclinical proof-of-principle study, the
      necrosis avid agent hypericin was investigated as a potential early indicator for
      therapeutic response after ethanol-mediated chemical ablation in murine liver
      tumors. MATERIALS AND METHODS: Seven mice bearing intrahepatic radiation-induced
      fibrosarcoma-1 tumors were intravenously injected with hypericin 1 hour before (n
      = 3) or 24 hours after (n = 4) intratumoral ethanol injection. Mice were
      euthanized 24 hours after hypericin injection and, taking advantage of the
      fluorescent property of the compound, the excised livers were investigated
      qualitatively and quantitatively by means of fluoromacroscopic and
      fluoromicroscopic examinations, colocalized with conventional histomorphology.
      RESULTS: Significant differences in hypericin fluorescence were found in
      necrosis, viable tumor and normal liver tissue in decreasing order (P < .05) (ie,
      in necrosis, mean fluorescence densities were about 4.5 times higher than in
      viable tumor and approximately 14 times higher than in normal liver). When
      hypericin was injected 1 hour before, maximal blood concentrations were achieved
      at the time of ethanol treatment, so that on ablation an outstanding
      extravasation took place in the entire necrotic area in comparison with
      accumulation of hypericin only at the peripheral zone of necrosis when it was
      injected 24 hours after ablation. CONCLUSIONS: Hypericin specifically enhanced
      the imaging contrast between necrotic and viable tissues and nonspecifically
      distinguished viable tumor from normal liver. Injection of hypericin shortly
      before ablation is more favorable than after ablation, because it circumvents
      difficulties with no-entry zones for hypericin and requires shorter intervals
      between ethanol ablation and imaging.

PMID- 18078914
TI  - Lowering the barriers inherent in translating advances in neuroimage analysis to
      clinical research applications.
AB  - RATIONALE AND OBJECTIVES: This article presents an initiative for the translation
      of advances in neuroimage analysis techniques to clinical research scientists.
      Our objective is to bridge the gap between scientific advances made by the
      biomedical imaging community and their widespread use in the clinical research
      community. Through national collaborative effort supported by the National
      Institutes of Health Roadmap, the integration of the most sophisticated
      algorithms into usable working open-source systems enables clinical researchers
      to have access to a broad spectrum of cutting edge analysis techniques. A
      critical step to maximize the long-term positive impact of this collaborative
      effort is to translate these techniques into new skills of clinical researchers.
      To address this challenge, we developed a methodology based on three criteria: a
      multidisciplinary approach, a balance between theory and common practice, and an
      immersive collaborative environment. The article illustrates our initiative
      through the exemplar case of diffusion tensor imaging tractography, and reports
      on our experience over the past two years of designing and delivering training
      workshops to more than 300 clinicians and scientists using the developed
      methodology.

PMID- 18078915
TI  - System-based practice: proposal for a comprehensive curriculum.

PMID- 18078916
TI  - Making preliminary radiographic reports available to referring clinicians:
      current status.
AB  - RATIONALE AND OBJECTIVES: To investigate current practice regarding the release
      of resident's preliminary imaging reports to physicians providing clinical care
      to patients. The second objective was to evaluate compliance with the American
      College of Radiology (ACR) practice guidelines. MATERIALS AND METHODS: With the
      assistance of the Society of Chairman of Academic Radiology Departments (SCARD),
      a survey was sent to its members. This survey asked if members felt that
      residents' preliminary reports should be released to referring physicians. If
      yes, the survey requested information as to how this was done and the mechanism
      by which the referring physicians were informed that the report was preliminary.
      RESULTS: Twenty-eight surveys were completed. Twenty-five respondents felt that
      preliminary reports should always be made easily available to referring
      physicians; three did not. In 25 of 28 institutions, the referring clinicians can
      obtain preliminary information by talking to the trainee face-to-face or by
      phone. In 12 institutions, clinicians could obtain preliminary reports by phoning
      into the hospital dictation system and listening to the dictated report. Twenty
      six of the 28 institutions permit referring clinicians to obtain preliminary
      reports by viewing/reading these reports in picture archiving and communication
      system (PACS) or hospital information system (HIS) systems, before they are
      finalized. CONCLUSIONS: Almost all academic radiology departments responding to
      this survey do make electronic trainee reports available to referring clinicians.
      Compliance with ACR guidelines is good, but not perfect. Most institutions no
      longer provide the ability to listen to the dictation.

PMID- 18078919
TI  - Mitochondrial toxicity and antioxidant activity of a prenylated flavonoid
      isolated from Dalea elegans.
AB  - The prenylated flavanone 2'-4'-dihidroxy-5'-(1" '-dimethylallyl)-6
      prenylpinocembrin) (6PP), isolated from the roots of Dalea elegans, shows
      antimicrobial activity. The aim of this study was to evaluate mitochondrial
      toxicity and antioxidant properties of 6PP. Addition of micromolar concentrations
      of 6PP to rat liver mitochondria, stimulated O2 uptake in state 4 and inhibited
      it in state 3 when malate-glutamate was the respiratory substrate, and inhibited
      O2 uptake in state 3 when succinate was the substrate. Highest concentration of
      6PP also inhibited O2 uptake in state 4 in the latter case; in both conditions,
      respiratory control index values were decreased. This flavanone collapsed the
      mitochondrial membrane potential in a concentration-dependent manner. 6PP also
      inhibited F0F1-ATPase activity in coupled mitochondria and in submitochondrial
      particles. In the latter, this compound also inhibited NADH oxidase and succinate
      dehydrogenase activities. HEp-2 cells were incubated for 24 h with 6PP in
      presence or absence of 0.5% albumin. As measured by reduction of the
      mitochondrial-related probe MTT, in the albumin-free condition, 6PP was cytotoxic
      in a concentration-dependent manner; on the other hand, albumin decreased 6PP
      effect. In addition, in rat liver microsomes 6PP: (1) inhibited the enzymatic
      lipid peroxidation, (2) exhibited significant scavenging activity, measured by
      DPPH reduction assay and (3) demonstrated significant antioxidant activity by
      decreasing the reduction of Mo(VI) to Mo(V). We suggest that 6PP impairs the
      hepatic energy metabolism by acting as mitochondrial uncoupler and by inhibiting
      enzymatic activities linked to the respiratory chain. 6PP also exerts both
      antioxidant and antiradical activities. Due to its cytotoxicity, this molecule,
      and its future structure developments, can be considered as a potentially
      promising therapeutic agent, for instance in cancer chemotherapy.

PMID- 18078920
TI  - Infants attribute goals even to biomechanically impossible actions.
AB  - Human infants readily interpret the actions of others in terms of goals, but the
      origins of this important cognitive skill are keenly debated. We tested whether
      infants recognize others' actions as goal-directed on the basis of their
      experience with carrying out and observing goal-directed actions, or whether
      their perception of a goal-directed action is based on the recognition of a
      specific event structure. Counterintuitively, but consistent with our prediction,
      we observed that infants appear to extend goal attribution even to
      biomechanically impossible actions so long as they are physically efficient,
      indicating that the notion of 'goal' is unlikely to be derived directly from
      infants' experience.

PMID- 18078921
TI  - A biomechanical model for real-time simulation of PMMA injection with haptics.
AB  - We have developed a computationally efficient rheological model to simulate
      polymethylmethacrylate (PMMA) injection into cancellous bone during percutaneous
      vertebroplasty. The model employs the Hagen-Poiseuille law to predict pressure
      drop across a delivery cannula with viscoelastic changes of curing PMMA modeled
      via a time and shear-rate-dependent power law. The power law was derived based on
      dynamic rheological testing of curing PMMA samples. In conjunction with a
      branching-pipe geometrical model that is reconstructed from micro-computed
      tomography scans of cancellous bone for estimating pressure changes during PMMA
      flow in bone, the method provides a fast estimation of overall injection
      pressure, and, hence, the reaction force during manual PMMA injection.

PMID- 18078922
TI  - Linkage of the US National Health Interview Survey to air monitoring data: an
      evaluation of different strategies.
AB  - The goal of this study is to describe linkages between the National Health
      Interview Survey (NHIS) and Environmental Protection Agency (EPA) air monitoring
      data, specifically how the linkage method affects characteristics and exposure
      estimates of study samples and estimated associations between exposure and
      health. In the USA, nationally representative health data are collected in the
      NHIS and annual air quality data are collected by the EPA. The linkage of these
      data for research is not straightforward and the choices made may introduce bias
      into results. The 2000-2003 NHIS and air quality data for six air pollutants were
      linked by residential block group and monitor location, which differ by
      pollutants. For each pollutant, three annual exposure variables were assigned to
      respondents: (1) average of all monitors in the county, (2) of monitors within a
      5-mile radius of the distance between block group and monitor, and (3) within a
      20-mile radius. Exposure estimates, study sample characteristics, and association
      between fine particle exposure and respondent-reported health status were
      compared for different geographic linkage methods. The results showed that study
      sample characteristics varied by geographic linkage method and pollutant linked.
      Generally, the fewer the NHIS respondents linked, the higher is the pollution
      exposure and lower is the percentage of non-Hispanic whites. After adjustment for
      sociodemographic and geographic factors, associations between fine particles and
      health status were generally comparable across study samples. Because exposure
      information is not available for all potential participants in an epidemiological
      study, selection effects should be considered when drawing inferences about air
      quality-health associations. With the current monitoring data system, the study
      sample is substantially reduced when linkage to multiple pollutants is performed.

PMID- 18078923
TI  - In vitro and in vivo effects of endothelin-1 and YM598, a selective endothelin ET
      A receptor antagonist, on the lower urinary tract.
AB  - We investigated the contractile response of the lower urinary tract to endothelin
      1 in vitro (rabbits) and in vivo (dogs). We also assessed the effects of a
      selective endothelin ET A receptor antagonist, (E)-N-[6-methoxy-5-(2
      methoxyphenoxy)[2, 2'-bipyrimidin]-4-yl]-2-phenylethenesulfonamide monopotassium
      salt (YM598), on endothelin-1-induced contractile responses. In the in vitro
      study, endothelin-1 induced contractile responses in isolated rabbit bladder
      base, urethra, and prostate tissues. YM598 (10(-7)-10(-5) M) antagonized these
      endothelin-1-induced contractile responses without affecting the maximal
      responses. In the in vivo study, endothelin-1 induced the elevation of non
      prostatic urethral pressure as well as prostatic urethral pressure even in the
      presence of tamsulosin (10 microg/kg, i.v.) in anesthetized male dogs. YM598 (0.1
      3 mg/kg, i.v.) inhibited these endothelin-1-induced contractile responses in a
      dose-dependent fashion. These results suggest that endothelin ET A receptors play
      an important role in the lower urinary tract contraction, and that the selective
      endothelin ET A receptor antagonist YM598 has ameliorating effects on various
      urinary dysfunctions, including benign prostatic hyperplasia.

PMID- 18078924
TI  - Involvement of cholecystokinin receptor in the inhibition of gastrointestinal
      motility by oxytocin in ovariectomized rats.
AB  - The effects of oxytocin on gastric emptying, gastrointestinal transit, and plasma
      levels of cholecystokinin (CCK) were studied in ovariectomized rats.
      Gastrointestinal motility was assessed in rats 15 min after intragastric
      instillation of a test meal containing charcoal and Na2 51CrO4. Gastric emptying
      was determined by measuring the amount of radiolabeled chromium contained in the
      small intestine as a percentage of the initial amount received. Gastrointestinal
      transit was evaluated by calculating the geometric center of distribution of the
      radiolabeled marker. Blood samples were collected for CCK radioimmunoassay. After
      administration of oxytocin (0.2-0.8 mg/kg), gastric emptying and gastrointestinal
      transit were inhibited, whereas plasma concentration of CCK was increased in a
      dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively
      attenuated the oxytocin-induced inhibition of gastric emptying and
      gastrointestinal transit. However, administration of atosiban alone had no effect
      on gastric emptying and gastrointestinal transit. The selective CCK1 receptor
      antagonists, devazepide and lorglumide, effectively attenuated the oxytocin
      induced inhibition of gastric emptying and gastrointestinal transit. L-365, 260,
      a selective CCK2 receptor antagonist, did not alter the oxytocin-induced
      inhibition of gastric emptying and gastrointestinal transit. These results
      suggest that oxytocin inhibits gastric emptying and gastrointestinal transit in
      ovariectomized rats via a mechanism involving the stimulation of CCK release and
      CCK1 receptor activation.

PMID- 18078925
TI  - Inhibitory mechanism of anti-allergic peptides in RBL2H3 cells.
AB  - Here we report the identification and functional characterization of several anti
      allergic peptides identified through biopanning of pooled sera of patients with
      various allergies. Several peptides, including LSYLLWRSRLP (LSY), LVAHVGAGGVL
      (LVA), RVSSCRGRNHIV (RVS), ETIGARWVRIE (ETI), TDGVTYTNDCL (TDG), RVVRYDADFWI
      (RVV), GFWCRRSGLVGV (GFW), were further characterized. These peptides inhibited
      the release of histamine from antigen-stimulated mast cells isolated from lung
      tissues of guinea pigs. Furthermore, the peptides inhibited calcium influx in
      ovalbumin-stimulated mast cells isolated from lung tissues of guinea pigs.
      Likewise, the peptides inhibited the release of beta-hexosaminidase from antigen
      stimulated rat basophilic leukemia (RBL2H3) cells and decreased calcium influx
      and intracellular reactive oxygen species production as well. We found that the
      peptides significantly decreased phosphorylation of extracellular regulated
      kinase (ERK) and that this was responsible for the decreased calcium influx and
      beta-hexosaminidase in antigen-stimulated RBL2H3 cells, suggesting that ERK plays
      an important role in allergic reactions. The peptides identified in this study
      also affected upstream signaling of allergic inflammation. In other words, these
      peptides decreased phosphorylation of Lyn, PKCalpha, and -delta. Lyn and PKC are
      known to be responsible for the phosphorylation of FcepsilonRI, in response to
      receptor aggregation. The peptides inhibited interaction between IgE and
      FcepsilonRI, suggesting that these peptides exert anti-allergic effects by
      inhibiting receptor cross-linking. These peptides also inhibited interaction
      between FcepsilonRI and PKCdelta. Taken together, these data suggest that
      peptides exert anti-allergic effect through the inhibition of upstream signaling,
      involving receptor cross-linking, and downstream multiple signaling.

PMID- 18078926
TI  - In vivo study on the effects of alpha1-adrenoceptor antagonists on intraurethral
      pressure in the prostatic urethra and intraluminal pressure in the vas deferens
      in male dogs.
AB  - Alpha-adrenoceptor antagonists are used worldwide for the treatment of voiding
      dysfunction associated with benign prostatic hyperplasia. Recently, abnormal
      ejaculation, an adverse effect associated with their use, has attracted
      attention. Here, we simultaneously investigated the effects of alpha(1)
      adrenoceptor antagonists on intraurethral pressure in the prostatic urethra and
      intraluminal pressure in the vas deferens in anesthetized male dogs, and compared
      their tissue selectivity. Phenylephrine, an alpha(1)-adrenoceptor agonist,
      induced simultaneous increases in intraurethral and intraluminal pressure.
      Alfuzosin, naftopidil, prazosin, silodosin and tamsulosin dose-dependently
      inhibited both responses. Comparison of ED(50) values in both tissues showed that
      silodosin had the highest selectivity for the vas deferens (7.5-fold), followed
      by naftopidil (4.3-fold), alfuzosin (3.8-fold), tamsulosin (2.6-fold) and
      prazosin (2.5-fold). These results suggest that alpha(1)-adrenoceptor antagonists
      inhibit contraction of not only the urethra but also the vas deferens in a dose
      dependent fashion, and that their high tissue selectivity for the vas deferens
      over the urethra may contribute to the incidence of abnormal ejaculation.

PMID- 18078927
TI  - Bolus injection of acetylcholine terminates atrial fibrillation in rats.
AB  - It is well established that a tonic increase in the availability of the atrial
      muscarinic K(+) channels, either by enhanced vagal tone or by steady infusion of
      a low-dose of cholinergic or adenosine receptor agonists, promotes the genesis of
      atrial fibrillation. Here, we aimed to test the hypothesis that bolus
      administration of a muscarinic receptor agonist would destabilize and terminate
      atrial arrhythmia by uniformly and transiently activating K(+) channels
      throughout the atria, and that if the agonist was rapidly hydrolysable, it would
      dissipate before the more tonic, pro-arrhythmic effects could take hold. The
      episodes of untreated atrial fibrillation, induced in anesthetized rats by
      programmed electrical stimulation via trans-esophageal bipolar catheter, lasted
      on average 8.6+/-2.2 min (n=32). Intravenous injection of a model hydrolysable
      muscarinic agonist, acetylcholine (0.2 mg/kg body weight), converted atrial
      fibrillation into sinus rhythm within 8.4+/-1.9 s (n=10, P<0.05). The termination
      of an atrial fibrillation episode was always accompanied by transient
      bradycardia; the sinus rhythm gradually accelerated and reached pre-atrial
      fibrillation values within 10-20 s of injection. In conclusion, our evidence
      indicates that bolus administration of rapidly hydrolysable muscarinic agonist
      could be an effective way to pharmacologically terminate atrial fibrillation and
      restore sinus rhythm.

PMID- 18078928
TI  - Cross talk of tumor necrosis factor-alpha and the renin-angiotensin system in
      tumor necrosis factor-alpha-induced plasminogen activator inhibitor-1 production
      from hepatocytes.
AB  - Tumor necrosis factor (TNF)-alpha and local activation of the renin-angiotensin
      system may contribute to insulin resistance and atherosclerosis. In this study,
      we investigated the involvement of these mediators in the liver. We found that
      the gene expression of renin-angiotensin system components, together with that of
      plasminogen activator inhibitor (PAI)-1, is upregulated in the liver of patients
      with obesity and type 2 diabetes. We next examined the role of the renin
      angiotensin system on TNF-alpha-induced PAI-1 production in the nonmalignant
      human hepatocyte cell line THLE-5b. THLE-5b cells expressed genes encoding renin
      angiotensin system components including angiotensinogen, angiotensin-converting
      enzyme (ACE), and angiotensin type 1 (AT(1)) receptor. ACE, angiotensinogen, and
      angiotensin AT(1) receptor mRNA expression were upregulated time-dependently by
      TNF-alpha. Moreover, angiotensin AT(1) receptor antagonist dose-dependently
      inhibited TNF-alpha-induced PAI-1 production. Interestingly, high-dose
      olmesartan, but not candesartan, reduced the increased expression of the
      angiotensin AT(1) receptor. These results suggest that TNF-alpha and the local
      renin-angiotensin system coordinately stimulate PAI-1 production in hepatocytes.
      Selective angiotensin AT(1) receptor antagonists inhibit both TNF-alpha- and
      angiotensin II-induced PAI-1 production in hepatocytes, suggesting a cross talk
      between both systems.

PMID- 18078929
TI  - Conversion of CD95 (Fas) Type II into Type I signaling by sub-lethal doses of
      cycloheximide.
AB  - CD95 (Fas/Apo-1)-mediated apoptosis was shown to occur through two distinct
      pathways. One involves a direct activation of caspase-3 by large amounts of
      caspase-8 generated at the DISC (Type I cells). The other is related to the
      cleavage of Bid by low concentration of caspase-8, leading to the release of
      cytochrome c from mitochondria and the activation of caspase-3 by the cytochrome
      c/APAF-1/caspase-9 apoptosome (Type II cells). It is also known that the protein
      synthesis inhibitor cycloheximide (CHX) sensitizes Type I cells to CD95-mediated
      apoptosis, but it remains contradictory whether this effect also occurs in Type
      II cells. Here, we show that sub-lethal doses of CHX render both Type I and Type
      II cells sensitive to the apoptogenic effect of anti-CD95 antibodies but not to
      chemotherapeutic drugs. Moreover, Bcl-2-positive Type II cells become strongly
      sensitive to CD95-mediated apoptosis by the addition of CHX to the cell culture.
      This is not the result of a restraint of the anti-apoptotic effect of Bcl-2 at
      the mitochondrial level since CHX-treated Type II cells still retain their
      resistance to chemotherapeutic drugs. Therefore, CHX treatment is granting the
      CD95-mediated pathway the ability to bypass the mitochondria requirement to
      apoptosis, much alike to what is observed in Type I cells.

PMID- 18078930
TI  - Genetic conversion of an SMN2 gene to SMN1: a novel approach to the treatment of
      spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA), a recessive, neuromuscular disease, is caused by a
      mutation or deletion in the SMN1 gene. The SMN2 gene is present in the same
      region of chromosome 5 and is similar in DNA sequence to SMN1 except for a T at
      position +6 of exon 7 that is likely the predominant functional difference
      between the two genes. This change alters RNA splicing which results in the
      removal of exon 7 from the mature mRNA; only 10% full-length transcripts are
      produced from the SMN2 gene. Our lab has shown that single-stranded
      oligonucleotides (ODN) can be used to repair genes with single base mutations
      within the context of the native chromosome. Here, we used SMN2-sequence-specific
      ODNs to direct the exchange of a T to a C in an SMA skin fibroblast cell line
      from a type 1 patient. The cells were transfected with ODNs of either 47 or 75
      bases in length and designed to hybridize to either the transcribed or non
      transcribed DNA strand of the SMN2 gene. We analyzed the genotype of these cells
      using a well-established Taqman probe-based PCR assay, restriction enzyme
      digestion, and cycle sequencing. Conversion of the SMN2 genotype to SMN1 was
      detected when the specific ODN was added. As a result, we observed an increase in
      production of full-length SMN mRNA, measured by qRT-PCR, and SMN protein,
      measured by western blotting. Finally, properly localized SMN protein was
      detected by the accretion of gemini of coiled bodies (gems) only in targeted
      cells. This is the first report of the use of ODNs to direct genetic conversion
      of SMN2 to SMN1 in human cells from SMA patients.

PMID- 18078931
TI  - Influence of dietary melatonin on photoreceptor survival in the rat retina: an
      ocular toxicity study.
AB  - Previous studies have shown that melatonin treatment increases the susceptibility
      of retinal photoreceptors to light-induced cell death. The purpose of this study
      was to evaluate under various conditions the potential toxicity of dietary
      melatonin on retinal photoreceptors. Male and female Fischer 344 (non-pigmented)
      and Long-Evans (pigmented) rats were treated with daily single doses of melatonin
      by gavage for a period of 14 days early in the light period or early in the dark
      period. In another group, rats were treated 3 times per week with melatonin early
      in the light period, and then exposed to high intensity illumination (1000-1500
      lx; HII) for 2h, and then returned to the normal cyclic lighting regime. At the
      end of the treatment periods, morphometric measurements of outer nuclear layer
      thickness (ONL; the layer containing the photoreceptor cell nuclei) were made at
      specific loci throughout the retinas. In male and female non-pigmented Fischer
      rats, melatonin administration increased the degree of photoreceptor cell death
      when administered during the nighttime and during the day when followed by
      exposure to HII. There were some modest effects of melatonin on photoreceptor
      cell death when administered to Fischer rats during the day or night without
      exposure to HII. Melatonin treatment caused increases in the degree of
      photoreceptor cell death when administered in the night to male pigmented Long
      Evans rats, but melatonin administration during the day, either with or without
      exposure to HII, had little if any effect on photoreceptor cell survival. In
      pigmented female Long-Evans rats, melatonin administration did not appear to have
      significant effects on photoreceptor cell death in any treatment group. The
      results of this study confirm and extend previous reports that melatonin
      increases the susceptibility of photoreceptors to light-induced cell death in non
      pigmented rats. It further suggests that during the dark period, melatonin
      administration alone (i.e., no HII exposure) to pigmented male rats may have a
      toxic effect on retinal cells. These results suggest that dietary melatonin, in
      combination with a brief exposure to high intensity illumination, induces
      cellular disruption in a small number of photoreceptors. Chronic exposure to
      natural or artificial light and simultaneous intake of melatonin may potentially
      contribute to a significant loss of photoreceptor cells in the aging retina.

PMID- 18078932
TI  - Peroxiredoxin 3 (PDRX3) is highly expressed in the primate retina especially in
      blue cones.
AB  - Oxidative stress and loss of mitochondrial function have been implicated in age
      related ocular diseases and thus studying enzymes involved in these processes may
      be of particular importance in these diseases. Peroxiredoxin III (PRDX3) is one
      of a family of six known peroxiredoxins which are known to protect cells against
      oxidative damage. PRDX3 is localized to the mitochondria and has been reported to
      be induced by hydrogen peroxide in aortic endothelial and lens epithelial cells.
      Using a highly specific commercially available antibody, PRDX3 was readily
      detected by immunoblot in monkey neural retina. Immunohistochemical analysis of
      human and monkey retina localized PRDX3 mainly to the photoreceptor inner
      segments, the outer and inner plexiform layers, and the ganglion cells. These are
      areas of known high mitochondrial content. In the monkey retina some of the cone
      inner segments were much more strongly labeled than others. Dual labeling
      experiments using specific anti-cone opsin antibodies determined that the high
      expressing cones were of the blue subtype. By contrast, in the human retina all
      of the cone inner segments were immunoreactive. This difference may be due to a
      postmortem induction of PRDX3 in the human sample. These results suggest that
      PRDX3 may be important in protecting photoreceptor mitochondria especially in
      blue cones.

PMID- 18078933
TI  - Pericytes and ocular diseases.
AB  - Pericytes are vascular mural cells which play multiple roles in angiogenesis and
      maintenance of blood vessel morphology and stability. In this review, we analyze
      recent data on the participation of pericytes in the pathogenesis of
      proliferative and non-proliferative diabetic retinopathy, as well as an emerging
      role in other angiogenic ocular diseases such as retinopathy of prematurity. Ways
      to exploit pericytes as targets for treatment of ocular diseases are discussed.

PMID- 18078934
TI  - Proliferative gliosis causes mislocation and inactivation of inwardly rectifying
      K(+) (Kir) channels in rabbit retinal glial cells.
AB  - Retinal glial (Muller) cells are proposed to mediate retinal potassium
      homeostasis predominantly by potassium transport through inwardly rectifying K(+)
      (Kir) channels. Retinal gliosis is often associated with a decrease in glial
      potassium conductance. To determine whether this decrease is caused by a
      downregulation of glial Kir channels, we investigated a rabbit model of
      proliferative vitreoretinopathy (PVR) which is known to be associated with
      proliferative gliosis. The membrane conductance of control Muller cells is
      characterized by large Kir currents whereas Muller cells of PVR retinas displayed
      an almost total absence of Kir currents. In control tissues, Kir2.1
      immunoreactivity is localized in the inner stem processes and endfeet of Muller
      cells whereas Kir4.1 immunoreactivity is largely confined to the Muller cell
      endfeet. In PVR retinas, there is a mislocation of Kir channel proteins, with
      Kir4.1 immunoreactivity detectable in Muller cell fibers throughout the whole
      retina, and a decrease of immunoreactivity in the cellular endfeet. Real-time PCR
      analysis revealed no alteration of the Kir4.1 mRNA levels in PVR retinas as
      compared to the controls but a slight decrease in Kir2.1 mRNA. Western blotting
      showed no difference in the Kir4.1 protein content between control and PVR
      retinas. The data suggest that proliferative gliosis in the retina is associated
      with a functional inactivation of glial Kir channels that is not caused by a
      downregulation of the channel proteins but is associated with their mislocation
      in the cell membrane.

PMID- 18078935
TI  - Colchicine attenuates compensation to negative but not to positive lenses in
      young chicks.
AB  - Optic nerve-sectioned (ONS) chick eyes are capable of emmetropisation, but these
      eyes also exhibit increased hyperopia without any visual manipulations, which
      suggests altered eye growth regulation. These altered growth changes may be
      related to the loss of retinal ganglion cells that follows nerve lesioning.
      Colchicine, which also destroys retinal ganglion cells in chicks, was used to
      further examine the effects of retinal ganglion cell loss on emmetropisation.
      Growth responses of +10D and -10D lens-wearing colchicine-injected eyes were
      compared to those of +10D and -10D lens-wearing saline-injected eyes,
      respectively. Changes after removal of lenses were also analysed. Prior to lens
      wear, colchicine-injected eyes exhibited longer optical axial lengths (OL;
      distance from cornea to retina; p=0.0185) but no differences in refractive error
      (RE; p=0.6588). Although myopic shifts were not significant for -10D lens-wearing
      colchicine-injected eyes (p=0.5913), but were for the saline-injected eyes
      (p=0.0034), these changes were not different (p=0.1646). However, -10D lens
      induced OL changes in colchicine-injected eyes showed insignificant (p=0.2214)
      and reduced (p=0.0102) changes compared to those of saline-injected eyes. +10D
      lens-treated colchicine-injected eyes showed significant hyperopic shifts
      (p<0.0001) and significant reductions in OL (p<0.0001) that were similar to those
      of saline-injected eyes (p=0.7990 and p=0.1495, respectively). Growth responses
      in eyes recovering from -10D lenses were minimal, with REs unaffected (p=0.3325),
      but OL reductions affected (p=0.0199) by colchicine. Colchicine-injected eyes
      recovering from +10D lenses showed significant myopic shifts (p=0.0003) and OL
      elongations (p<0.0001) that were similar to those of saline-injected eyes
      (p=0.3999 and p=0.4731, respectively). The results showing that colchicine
      suppresses the ability to respond to negative lenses but leaves compensation to
      positive lenses relatively unchanged, are opposite to those of optic nerve
      sectioned eyes. We speculate that the differences are probably related to the way
      retinal cells are lost.

PMID- 18078937
TI  - Photoperiod alters central distribution of estrogen receptor alpha in brain
      regions that regulate aggression.
AB  - Testosterone or its metabolite, estrogen, regulates aggression in males of many
      mammalian species. Because plasma testosterone levels are typically positively
      correlated with both aggression and reproduction, aggression is expected to be
      higher when males are in reproductive condition. However, in some photoperiodic
      species such as Siberian hamsters (Phodopus sungorus), males are significantly
      more aggressive in short day lengths when the testes are regressed and
      circulating testosterone concentrations are reduced. These results led to the
      formation of the hypothesis that aggression is modulated independently of
      circulating steroids in Siberian hamsters. Thus, recent studies have been
      designed to characterize the role of other neuroendocrine factors in modulating
      aggression. However, aggression may be mediated by testosterone or estrogen
      despite basal concentrations of these steroids by increasing sensitivity to
      steroids in specific brain regions. Consistent with this hypothesis, we found
      that males housed under short days have increased expression of estrogen receptor
      alpha in the bed nucleus of the stria terminalis, medial amygdala, and central
      amygdala. Neural activation in response to an aggressive encounter was also
      examined across photoperiod.

PMID- 18078938
TI  - Experience with a comprehensive university hospital-based infertility program in
      Nigeria.
AB  - OBJECTIVE: To assess outcome at an infertility management center in Nigeria.
      METHODS: Diagnoses were made for 1948 consecutive couples following the World
      Health Organization guideline on the investigation of infertile couples,
      treatment was provided, and the couples were followed up over a 10-year period.
      RESULTS: The infertility was primary in 14.3% and secondary in 85.7% of cases.
      Treatment failed in 59.9% and succeeded in 40.1% of cases, resulting in pregnancy
      for 13.5% of the couples with female infertility factors alone, 6.5% of the
      couples with male infertility factors alone, and 3.6% of those with both male and
      female factors. The pregnancy rate was 16.6% for couples with idiopathic
      infertility. CONCLUSION: Pregnancy outcome was relatively poor because
      conventional treatments did not cure the most prevalent causes of infertility,
      and assisted reproductive technology is therefore advocated.

PMID- 18078936
TI  - Prevention of paclitaxel-evoked painful peripheral neuropathy by acetyl-L
      carnitine: effects on axonal mitochondria, sensory nerve fiber terminal arbors,
      and cutaneous Langerhans cells.
AB  - Prophylactic treatment with acetyl-L-carnitine (ALCAR) prevents the neuropathic
      pain syndrome that is evoked by the chemotherapeutic agent, paclitaxel. The
      paclitaxel-evoked pain syndrome is associated with degeneration of the
      intraepidermal terminal arbors of primary afferent neurons, with the activation
      of cutaneous Langerhans cells, and with an increased incidence of swollen and
      vacuolated axonal mitochondria in A-fibers and C-fibers. Previous work suggests
      that ALCAR is neuroprotective in other nerve injury models and that it improves
      mitochondrial dysfunction. Thus, we examined whether the prophylactic efficacy of
      ALCAR was associated with the prevention of intraepidermal terminal arbor
      degeneration, the inhibition of Langerhans cell activation, or the inhibition of
      swelling and vacuolation of axonal mitochondria. In animals with a confirmed
      ALCAR effect, we found no evidence of a neuroprotective effect on the paclitaxel
      evoked degeneration of sensory terminal arbors or an inhibition of the paclitaxel
      evoked activation of Langerhans cells. However, ALCAR treatment completely
      prevented the paclitaxel-evoked increase in the incidence of swollen and
      vacuolated C-fiber mitochondria, while having no effect on the paclitaxel-evoked
      changes in A-fiber mitochondria. Our results suggest that the efficacy of
      prophylactic ALCAR treatment against the paclitaxel-evoked pain may be related to
      a protective effect on C-fiber mitochondria.

PMID- 18078939
TI  - Resectoscope or Versapoint for hysteroscopic metroplasty.
AB  - OBJECTIVE: To assess the feasibility, safety, and reproductive outcome of
      hysteroscopic metroplasty using the Versapoint device compared with the
      resectoscope using the Collins loop. METHODS: Sixty-three women diagnosed with
      partial septate uterus were included in the study. Forty-two women underwent
      hysteroscopic metroplasty using Versapoint and 21 women had the procedure using
      the resectoscope. Operating time, complications, pregnancy rate, and mode of
      delivery were recorded. Data were analyzed with the Mann-Whitney test. RESULTS:
      Operating time was 20.5 min for the resectoscope group and 15.4 min for the
      Versapoint group (P<0.05). Pregnancy rate, delivery rate, and spontaneous
      abortions were similar in both groups. CONCLUSION: Operative hysteroscopy with
      Versapoint does not require cervical dilation, thus avoiding cervical
      incompetence, cervical lacerations, and uterine perforation. The Versapoint
      technique is a safe and effective alternative to the resectoscope. It could be
      used predominantly in nulligravida women, especially in those with cervical canal
      stenosis.

PMID- 18078940
TI  - Conjugated and non-conjugated octadecaenoic acids affect differently intestinal
      acyl coenzyme A: cholesterol acyltransferase activity.
AB  - We investigated the relative hypocholesterolemic activity of linoleic acid (LA),
      conjugated linoleic acid (CLA), alpha-linolenic acid (LN) and conjugated
      linolenic acid (CLN) in hamsters. Five groups of hamsters (n=10 each) were fed
      either the control diet or one of the four fatty acids-supplemented diets for 6
      weeks. Results demonstrated that the four octadecaenoic acids decreased plasma
      cholesterol differently, with CLA being the most effective. Western blotting and
      RT-PCR analysis demonstrated that the four octadecaenoic acids had no effect on
      sterol regulatory element binding protein-2 (SREBP-2), liver X receptor (LXR), 3
      hydroxy-3-methylglutary-CoA reductase (HMGR), LDL receptor (LDLR), and
      cholesterol-7alpha-hydroxylase (CYP7A1). However, the four octadecaenoic acids
      increased the excretion of fecal neutral sterols with CLA being most effective
      followed by LN, LA and CLN, suggesting they all differentially affect cholesterol
      absorption. Dietary CLA was associated with the least intestinal acyl coenzyme A:
      cholesterol acyltransferase (ACAT) activity followed by LN, LA and CLN in a
      decreasing trend. Since esterification of cholesterol is catalyzed by intestinal
      ACAT, and is a rate-limiting step in cholesterol absorption, it was concluded
      that the varying effects of CLA, LN, LA and CLN on blood cholesterol were
      mediated, at least in part, by their inhibition on intestinal ACAT activity.

PMID- 18078941
TI  - Treadmill exercise test with dual isotope scintigraphy documents the second
      window of preconditioning in humans.
AB  - BACKGROUND: In experimental studies, two windows of preconditioning have been
      identified, one lasting 1-2h and a second one (SWOP) starting 24h later and
      lasting 3-4 days. We sought to document SWOP in humans, using scintigraphy as an
      objective method of imaging. METHODS: Nineteen male patients, aged 62+/-7 years
      with documented coronary artery disease underwent two treadmill exercise tests
      (at baseline and 30 h later) and three tomographic perfusion studies (during the
      first exercise test, during the redistribution phase 4 h later and during the
      second exercise test 30 h later) with two different isotopes. Thallium-201 (TL)
      was used for the assessment of the first exercise and the redistribution phase,
      whereas technetium 99m tetrofosmin (TET) was used 30 h later for the evaluation
      of SWOP. Both exercise tests terminated at the same time-point. The distribution
      of TL and TET uptake was analyzed qualitatively using a 5-point scale on a 17
      segment myocardial model. Perfusion score was derived by summing the uptake of
      all segments, while total perfusion defect by subtracting the polar map of the
      first exercise test from that of the second exercise test. RESULTS: Anginal
      symptoms were reported by 13 of 19 patients (68%) in the first test versus only 2
      of 19 patients (11%) in the second one (p=0.001). The mean maximum ST segment
      depression was significantly reduced in the second test (from 1.58+/-0.73 to
      0.82+/-1.07, p<0.01). Similarly, the perfusion score was reduced from 21.0+/-7.4
      to 14.2+/-5.7 in the second test (p<0.01) and the total defect size from 24+/-16
      to 12+/-14 (p<0.01). CONCLUSION: The myocardial perfusion improvement during the
      second exercise study confirms objectively the existence of SWOP in humans.

PMID- 18078942
TI  - Effect of multiple freeze-thaw cycles on intervertebral dynamic motion
      characteristics in the porcine lumbar spine.
AB  - Fresh frozen spine specimens are commonly used in biomechanical investigations of
      the spine. Since many study designs require staged preparation and testing, the
      effect of multiple freeze-thaw cycles on motion behavior should be understood.
      The objective of this study was to investigate the effect of multiple freeze-thaw
      cycles on the biomechanical parameters measured during dynamic pure moment
      loading. Ten porcine lumbar motion segments were harvested immediately after
      death and potted in acrylic fixtures. Specimens were tested in continuous pure
      moment flexion-extension, lateral flexion, and rotation cycles up to a limit of
      +/-5Nm. Moment-angular displacement data were analyzed and parameters quantified
      including range of motion, elastic zone, transitional zone (neutral region) size
      and slope, and width of the hysteresis loop. All specimens were tested at
      baseline and after each of three subsequent cycles of freezing and thawing. The
      transitional zone size decreased and the transitional zone slope increased during
      flexion-extension and lateral bending after the initial freeze-thaw cycle. These
      parameters were not altered after subsequent cycles. No significant change was
      observed in the elastic zone or width of hysteresis loop. Although freezing
      porcine spine specimens increased the stiffness in the neutral region of motion,
      up to three subsequent cycles of freezing and thawing did not further affect
      these motion characteristics. This suggests that data obtained from porcine
      spines which have been frozen and thawed multiple times are stable after initial
      freezing.

PMID- 18078943
TI  - Gait and neuromuscular pattern changes are associated with differences in knee
      osteoarthritis severity levels.
AB  - Knee osteoarthritis (OA) is a multifactoral, progressive disease process of the
      musculoskeletal system. Mechanical factors have been implicated in the
      progression of knee OA, but the role of altered joint mechanics and neuromuscular
      control strategies in progressive mechanisms of the disease have not been fully
      explored. Previous biomechanical studies of knee OA have characterized changes in
      joint kinematics and kinetics with the disease, but it has been difficult to
      determine if these biomechanical changes are involved in the development of
      disease, are in response to degenerative changes in the joint, or are
      compensatory mechanisms in response to these degenerative changes or other
      related factors as joint pain. The goal of this study was to explore the
      association between biomechanical changes and knee OA severity in an effort to
      understand the changing role of biomechanical factors in the progression of knee
      OA. A three-group cross-sectional model was used that included asymptomatic
      subjects, subjects clinically diagnosed with moderate knee OA and severe knee OA
      subjects just prior to total joint replacement surgery. Principal component
      analysis and discriminant analysis were used to determine the combinations of
      electromyography, kinematic and kinetic waveform pattern changes at the knee, hip
      and ankle joints during gait that optimally separated the three levels of
      severity. Different biomechanical mechanisms were important in discriminating
      between severity levels. Changes in knee and hip kinetic patterns and rectus
      femoris activation were important in separating the asymptomatic and moderate OA
      gait patterns. In contrast, changes in knee kinematics, hip and ankle kinetics
      and medial gastrocnemius activity were important in discriminating between the
      moderate and severe OA gait patterns.

PMID- 18078944
TI  - On the effect of parent-aneurysm angle on flow patterns in basilar tip aneurysms:
      towards a surrogate geometric marker of intra-aneurismal hemodynamics.
AB  - As a part of previous computational fluid dynamic (CFD) validation studies,
      particle image velocimetry (PIV) of two anatomically realistic basilar artery tip
      aneurysm models revealed two distinct types of flow (one of which has yet to be
      reported in the literature), characterized by the location and strength of the
      intra-aneurismal vortex. We hypothesized that these distinct "hemodynamic
      phenotypes" could be anticipated by a simple geometric parameter: the angle of
      the aneurysm bulb relative to the parent artery. An idealized basilar tip
      aneurysm model was constructed to allow independent control of this angle, and
      CFD simulations were carried out for angles ranging from 2 degrees to 30 degrees
      , these extremes corresponding to the angles measured from the two anatomically
      realistic models. The gross hemodynamics predicted by the idealized model for 2
      degrees and 30 degrees were consistent with those seen in the corresponding
      anatomically realistic models. For the idealized model, the flow type switched at
      an angle between 8 degrees and 12 degrees . Sensitivity studies suggested that,
      near these angles, the hemodynamic phenotype was sensitive to inflow momentum.
      Outside this range, however, the parent-bulb angle appeared to be a robust
      predictor of hemodynamic phenotype. Our findings suggest that blood flow dynamics
      in basilar artery tip aneurysms fall into one of the two broad phenotypes, each
      subject to distinct hemodynamic forces. That the general features of these flow
      types may be anticipated by a relatively simple-to-measure geometric parameter
      could help ease the introduction of hemodynamic information into routine clinical
      decision-making.

PMID- 18078945
TI  - Protein partitioning in poly(ethylene glycol)/sodium polyacrylate aqueous two
      phase systems.
AB  - The partition of hemoglobin, lysozyme and glucose-6-phosphate dehydrogenase
      (G6PDH) in a novel inexpensive aqueous two-phase system (ATPS) composed by
      poly(ethylene glycol) (PEG) and sodium polyacrylate (NaPA) has been studied. The
      effect of NaCl and Na(2)SO(4), pH and PEG molecular size on the partitioning has
      been studied. At high pH (above 9), hemoglobin partitions strongly to the PEG
      phase. Although some precipitation of hemoglobin occurs, high recovery values are
      obtained particularly for lysozyme and G6PDH. The partitioning forces are
      dominated by the hydrophobic and electrochemical (salt) effects, since the
      positively charged lysozyme and negatively charged G6PDH partitions to the non
      charged PEG and the strongly negatively charged polyacrylate enriched phase,
      respectively.

PMID- 18078946
TI  - Development of a comprehensive multidimensional liquid chromatography system with
      tandem mass spectrometry detection for detailed characterization of recombinant
      proteins.
AB  - A multidimensional comprehensive liquid-phase separation system (2DLC) coupled on
      line to an electrospray-ionization time-of-flight (ESI-TOF) mass spectrometer
      (MS) was used to resolve structural alterations and/or post-translational
      modifications for detailed protein characterization. The system described in this
      work consists of cation-exchange chromatography in the first dimension and
      reversed-phase chromatography in the second dimension. A unique spiked gradient
      was employed in the first dimension to enhance recovery of peptides. This
      combination of separation followed by MS detection offered the advantages of
      unique selectivity and high efficiency of the separation methods combined with
      the mass specificity and sensitivity of MS. During the course of this study it
      was determined that altered or modified peptides were shown to be better resolved
      than during a one-dimensional separation. The 2DLC/ESI methodology allowed for a
      comprehensive evaluation of post-translational modifications and chemical
      reactions of recombinant proteins, providing a meaningful evaluation of product
      quality that was not possible with other current analytical approaches. In
      addition, the system can be used to provide sequence coverage of complex
      proteins.

PMID- 18078947
TI  - Optimization of steady state recycling parameters utilizing polarimetry in chiral
      separations.
AB  - Processing gram to kilogram quantities of target analytes has led to the
      exploration of several high-throughput separation techniques. Among those
      investigated is steady state recycling (SSR). Similar to simulated moving bed
      (SMB) fractions are collected from the leading and trailing edges of a
      chromatographic profile while sample material is injected into the interior.
      Purifying large amounts of sample in the semi-preparative stage is ideal for
      these groups. SSR allows for development of methods capable of separating 50 g to
      kilograms and even greater amounts of product efficiently. Using polarimetry to
      optimize the SSR method further improves the efficiency of method development,
      providing comprehensive data leading to incisive development decisions. Accurate
      sample injection allowed continual 99% enantiomer separation after polarimetry
      optimization. We have developed an efficient SSR optimization methodology that
      offers rapid development of chiral separation by SSR.

PMID- 18078948
TI  - Development and validation of a quantitative gas chromatography-mass spectrometry
      method for the detection of endogenous androgens in mouse urine.
AB  - A quantitative method based on gas chromatography-mass spectrometry (GC-MS) has
      been developed for the detection of 16 endogenous androgens in the urine of mice.
      The substances are extracted from 100 microL urine with freshly distilled diethyl
      ether after alkalinisation. The substances are derivatised with a mixture of N
      methyl-N-trimethylsilyltrifluoroacetamide/NH(4)I/ethanethiol (383/1/2, v/w/v) and
      detected by GC-MS in the selected ion monitoring mode. The results of the method
      validation indicate good linearity, accuracy and precision, making the method
      suitable for the quantification of endogenous androgens in mouse urine. The
      selectivity of the method showed that no interfering peaks were observed at the
      retention times of the analytes. The method allows for the direct quantification
      and identification of testosterone and 15 other endogenous androgens at low
      concentrations (ng/mL) in mouse urine. The applicability of the method is shown
      by the analysis of a mouse urine. Several endogenous steroids could be detected.

PMID- 18078949
TI  - Adsorption behavior of anionic polyelectrolyte for chemical mechanical polishing
      (CMP).
AB  - In this work, we investigated the adsorption characteristics of anionic
      polyelectrolytes, which are used in shallow trench isolation chemical mechanical
      polishing with ceria abrasives. Specifically, the adsorption isotherms and chain
      conformation of anionic polyelectrolytes were studied in order to elucidate the
      difference in removal rates of silicon dioxide (SiO2) and silicon nitride (Si3N4)
      layers and the high selectivity characteristics of ceria slurry. Adsorption
      isotherms, FT-IR spectroscopy and contact angle measurements revealed that the
      anionic polyelectrolyte additives had much better adsorption affinities for the
      Si3N4 surface than for the SiO2 surface. Moreover, blanket wafer polishing
      results were successfully correlated with the adsorption isotherms of
      polyelectrolytes on the oxide particle suspensions.

PMID- 18078950
TI  - Children's sensitivity to circular explanations.
AB  - The ability to evaluate the quality of explanations is an essential part of
      children's intellectual growth. Explanations can be faulty in structural ways
      such as when they are circular. A circular explanation reiterates the question as
      if it were an explanation rather than providing any new information. Two
      experiments (N=77) examined children's preferences when faced with circular and
      noncircular explanations. The results demonstrate that a preference for
      noncircular explanations is present, albeit in a fragile form, by 5 or 6 years of
      age and that it appears robustly by 10 years of age. Thus, the ability to
      evaluate the quality of explanations based on structural grounds appears to
      develop rapidly during the elementary school years.

PMID- 18078951
TI  - An enzyme-linked immunosorbent assay (ELISA) for quantification of mouse
      surfactant protein D (SP-D).
AB  - Surfactant protein D (SP-D) is a pattern recognition molecule of the collectin
      family of C-type lectins. It is found in the airways and at mucosal surfaces. SP
      D is part of the innate immune system where it neutralizes and leads to
      elimination of microorganisms. It regulates the functions of other innate immune
      cells, such as macrophages and neutrophils. It also modulates the adaptive immune
      response by interacting with antigen-presenting cells and T cells. Monoclonal
      anti-mouse-SP-D antibodies were raised from SP-D deficient mice using recombinant
      SP-D as antigen. Ten monoclonal antibodies were characterized and validated for
      use in sandwich enzyme-linked immunosorbent assay (ELISA). Based on two of these,
      we established an ELISA that allows for measurements of mouse SP-D in various
      body fluids. The final ELISA was optimized and calibrated with a standard of
      purified recombinant mouse SP-D, which was analyzed by quantitative amino acid
      analysis. The ELISA was validated with respect to parallelism, recovery, intra-
      and inter-assay variation. The practical working range was estimated to be 1.9
      200 ng/ml. We measured SP-D in lung lavage to an average concentration of 435
      ng/ml (3-ml lavage), and in mouse vaginal fluid (1-ml lavage) to an average
      concentration of 94 ng/ml, but could not detect SP-D in the serum or plasma of
      healthy mice (<3.8 ng/ml). With this ELISA, it will be possible to study the
      regulation of SP-D in various mouse models and upon various stimuli.

PMID- 18078952
TI  - First record of a nematode Metastrongyloidea (Aelurostrongylus abstrusus larvae)
      in Achatina (Lissachatina) fulica (Mollusca, Achatinidae) in Brazil.
AB  - Achatina (Lissachatina) fulica was introduced in Brazil in the 1980s for
      commercial purposes ("escargot" farming) and nowadays, mainly by human activity,
      it is widespread in at least 23 out of 26 Brazilian states and Brasilia,
      including the Amazonian region and natural reserves, where besides a general
      nuisance for people it is a pest and also a public health concern, since it is
      one of the natural intermediate host of Angiostrongylus cantonensis, ethiological
      agent of the meningoencephalitis in Asia. As Brazil is experiencing the explosive
      phase of the invasion, the Laboratorio de Malacologia do Instituto Oswaldo
      Cruz/Fiocruz has been receiving samples of these molluscs for identification and
      search for Angiostrongylus cantonensis and Angiostrongylus costaricensis larvae.
      While examining samples of A. fulica different nematode larvae were obtained,
      including Aelurostrongylus, whose different species are parasites of felids,
      dogs, primates, and badger. Morphological and morphometric analyses presented
      herein indicated the species Aelurostrongylus abstrusus, as well as the
      occurrence of other nematode larvae (Strongyluris-like) found in the interior of
      the pallial cavity of A. fulica. This is the first report in Brazil of the
      development of A. abstrusus infective larvae in A. fulica evidencing the
      veterinary importance of this mollusc in the transmission of A. abstrusus to
      domestic cats. Since the spread of A. fulica is pointed out in the literature as
      one of the main causative spread of the meningoencephalitis caused by A.
      cantonensis the authors emphasize the need of sanitary vigilance of snails and
      rats from vulnerable areas for A. cantonensis introduction as the port side
      areas.

PMID- 18078953
TI  - Oxidative injury induces selective rather than global inhibition of proteasomal
      activity.
AB  - Oxidative injury has been found to be associated with proteasomal inactivity. In
      this study, the extent of oxidative damage and its effects on proteasomal
      function has been critically assessed. Left anterior descending coronary artery
      was occluded (ischemia) and reperfused with or without preconditioning in male
      Sprague-Dawley rats. For further validation, H9c2 cardiac myoblasts cultures were
      used. We demonstrate that ischemia-reperfusion causes extensive endoplasmic
      reticulum stress as evident from the degradation of GRP78 transcript followed by
      its rapid induction. Western blot analysis and immunohistochemistry showed that
      increasing duration of ischemia and reperfusion causes accumulation of
      phosphorylated IkappaB (p-IkappaB), thereby suggesting proteasomal inactivity.
      However, similar analysis for Nrf2, a key mediator of antioxidant defense, showed
      sustained activation, suggesting intact proteasomal function. Preconditioning of
      the myocardium preserves the degradation of p-IkappaB, suggesting effective
      functioning of proteasome after preconditioning. Further analysis with specific
      proteosomal inhibitors like epoxomicin (100 nM, inhibits chymotrypsin-like
      activities of proteasomes) and lactacystin (2 microM, inhibits chymotrypsin as
      well as some trypsin-like activities of proteasomes) suggests that degradation of
      p-IkappaB and Keap-1 in the proteasome occurs by independent mechanisms. This
      study gives further insight into interrelationship between oxidative injury and
      catalytic function of the proteasome in heart, where oxidative injury causes
      selective rather than global inhibition of proteasome.

PMID- 18078954
TI  - Structural basis for the interaction between focal adhesion kinase and CD4.
AB  - Focal adhesion kinase (FAK) and CD4 fulfil vital functions in cellular signal
      transduction: FAK is a central component in integrin signalling, whereas CD4
      plays essential roles in the immune defence. In T lymphocytes, FAK and CD4
      localise to the same signalling complexes after stimulation by either the human
      immunodeficiency virus (HIV) gp120 glycoprotein or an antigen, suggesting the
      concerted action of FAK and CD4 in these cells. Using crystallography and
      microcalorimetry, we here show that the focal adhesion targeting (FAT) domain of
      FAK binds specifically to the CD4 endocytosis motif in vitro. This FAT-CD4
      complex is structurally and thermodynamically similar to the one FAT forms with
      paxillin LD motifs. The CD4 binding site on FAT presents the same features as the
      established CD4 binding site on the HIV-1 Nef protein. The binding of FAT to CD4
      is incompatible with the binding of Lck to CD4. We further show that HIV-1 gp120
      triggers the association of CD4 with FAK in T cells, under conditions that are
      known to dissociate Lck from CD4. Our results suggest that the FAK-CD4 complex
      represents an alternative route for eliciting T-cell-specific signals and that it
      links gp120 engagement to distinctive T-cell signalling during HIV infection. In
      infected cells, HIV-1 Nef may displace FAK from CD4 to protect the cells from
      apoptosis.

PMID- 18078955
TI  - Understanding the structural basis for substrate and inhibitor recognition in
      eukaryotic GH11 xylanases.
AB  - Endo-beta1,4-xylanases (xylanases) hydrolyse the beta1,4 glycosidic bonds in the
      backbone of xylan. Although xylanases from glycoside hydrolase family 11 (GH11)
      have been extensively studied, several issues remain unresolved. Thus, the
      mechanism by which these enzymes hydrolyse decorated xylans is unclear and the
      structural basis for the variation in catalytic activity within this family is
      unknown. Furthermore, the mechanism for the differences in the inhibition of
      fungal GH11 enzymes by the wheat protein XIP-I remains opaque. To address these
      issues we report the crystal structure and biochemical properties of the
      Neocallimastix patriciarum xylanase NpXyn11A, which displays unusually high
      catalytic activity and is one of the few fungal GH11 proteins not inhibited by
      XIP-I. Although the structure of NpXyn11A could not be determined in complex with
      substrates, we have been able to investigate how GH11 enzymes hydrolyse decorated
      substrates by solving the crystal structure of a second GH11 xylanase, EnXyn11A
      (encoded by an environmental DNA sample), bound to ferulic acid-1,5
      arabinofuranose-alpha1,3-xylotriose (FAX(3)). The crystal structure of the
      EnXyn11A-FAX(3) complex shows that solvent exposure of the backbone xylose O2 and
      O3 groups at subsites -3 and +2 allow accommodation of alpha1,2-linked 4-methyl-D
      glucuronic acid and L-arabinofuranose side chains. Furthermore, the ferulated
      arabinofuranose side chain makes hydrogen bonds and hydrophobic interactions at
      the +2 subsite, indicating that the decoration may represent a specificity
      determinant at this aglycone subsite. The structure of NpXyn11A reveals potential
      -3 and +3 subsites that are kinetically significant. The extended substrate
      binding cleft of NpXyn11A, compared to other GH11 xylanases, may explain why the
      Neocallimastix enzyme displays unusually high catalytic activity. Finally, the
      crystal structure of NpXyn11A shows that the resistance of the enzyme to XIP-I is
      not due solely to insertions in the loop connecting beta strands 11 and 12, as
      suggested previously, but is highly complex.

PMID- 18078956
TI  - An ADP/ATP-specific mitochondrial carrier protein in the microsporidian
      Antonospora locustae.
AB  - The mitochondrion is one of the defining characteristics of eukaryotic cells, and
      to date, no eukaryotic lineage has been shown to have lost mitochondria entirely.
      In certain anaerobic or microaerophilic lineages, however, the mitochondrion has
      become severely reduced that it lacks a genome and no longer synthesizes ATP. One
      example of such a reduced organelle, called the mitosome, is found in
      microsporidian parasites. Only a handful of potential mitosomal proteins were
      found to be encoded in the complete genome of the microsporidian Encephalitozoon
      cuniculi, and significantly no proteins of the mitochondrial carrier family were
      identified. These carriers facilitate the transport of solutes across the inner
      mitochondrial membrane, are a means of communication between the mitochondrion
      and cytosol, and are abundant in organisms with aerobic mitochondria. Here, we
      report the characterization of a mitochondrial carrier protein in the
      microsporidian Antonospora locustae and demonstrate that the protein is
      heterologously targeted to mitochondria in Saccharomyces cerevisiae. The protein
      is phylogenetically allied to the NAD(+) transporter of S. cerevisiae, but we
      show that it has high specificity for ATP and ADP when expressed in Escherichia
      coli. An ADP/ATP carrier may provide ATP for essential ATP-dependent mitosomal
      processes such as Hsp70-dependent protein import and export of iron-sulfur
      clusters to the cytosol.

PMID- 18078957
TI  - Impact of obesity in patients with urolithiasis and its prognostic usefulness in
      stone recurrence.
AB  - PURPOSE: Recent studies have suggested an increased prevalence of urolithiasis
      and recurrence associated with obesity. We assessed the influence of obesity on
      stone risk factors as well as on stone recurrence. MATERIALS AND METHODS: A
      database of patient history, body mass index, and serum and urine chemistry was
      analyzed for 704 consecutive stone formers (467 first time stone formers and 247
      recurrent stone formers). Obesity was defined as body mass index greater than 25
      kg/m(2). The effect of obesity on stone risk factors and recurrence were
      stratified according to stone episodes. Of these, 163 (23.2%) patients who had
      been followed for more than 36 months (median 54, range 5 to 148) were included
      in recurrence analysis. RESULTS: Obesity was significantly associated with stone
      episodes (p = 0.043). Obese stone formers excreted increased amounts of sodium,
      calcium, uric acid and citrate, while the urinary pH in a 24-hour urine sample
      was decreased compared to nonobese stone formers (p <0.05, respectively). Stone
      analysis revealed that uric acid stone was significantly more commonly found in
      the obese patients (p = 0.046). Multivariate Cox regression model stratified by
      stone episodes revealed that obesity (HR 2.572, 95% CI 1.376-4.807, p = 0.003)
      was the only strong predictor of stone recurrence in first time stone formers. No
      association between obesity and stone recurrence was detected in recurrent stone
      formers. Kaplan-Meier curves showed identical results. CONCLUSIONS: This study
      reveals that obesity is associated with metabolic alterations and urinary stone
      recurrence. Weight control may be considered one of the preventive modalities
      against recurrent stone formation, especially in first time stone formers.

PMID- 18078958
TI  - To stent or not to stent perioperatively the ureteroileal anastomosis of ileal
      orthotopic bladder substitutes and ileal conduits? Results of a prospective
      randomized trial.
AB  - PURPOSE: We evaluated the impact of stenting the ureteroileal anastomosis on its
      competence, upper urinary tract dilatation, gastrointestinal recovery, metabolic
      parameters and patency rate after cystectomy with ileal bladder substitution or
      ileal conduit. MATERIALS AND METHODS: A total of 54 patients (37 with an ileal
      bladder substitute and 17 with an ileal conduit) were prospectively randomized
      into 2 groups, with (29) or without (25) perioperative stenting of the
      ureteroileal anastomosis. In all cases an end-to-side ureteroileal refluxing
      anastomosis was performed. The stents were removed after 5 to 10 days. The
      parameters assessed postoperative days 1, 3 and 7 were creatinine concentration
      from the wound drains, upper urinary tract dilatation, time to bowel function
      recovery, serum creatinine, as well as urea and incidence of metabolic acidosis.
      RESULTS: Median patient age was 68 years (range 45 to 85). Urine leak on
      postoperative day 1 was more frequent in those anastomoses without stents, and on
      postoperative days 3 and 7 the values were comparable. Stenting of the
      ureteroileal anastomosis resulted in significantly decreased early postoperative
      upper urinary tract dilatation, improved recovery of bowel function and decreased
      metabolic acidosis. In either group no patient had clinical evidence of
      ureteroileal anastomotic stricture during the early postoperative period. Three
      patients with perioperative stenting required surgical or endoscopic treatment
      for a stricture of the ureteroileal anastomosis during the 12-month followup.
      CONCLUSIONS: Stenting of the ureteroileal anastomosis allows for significantly
      less frequent incidence of early postoperative dilatation of the pelvicaliceal
      system, bowel activity resumes significantly earlier and metabolic acidosis is
      significantly less frequent.

PMID- 18078959
TI  - Arterio-ureteral fistula: 11 new cases of a wolf in sheep's clothing.
AB  - PURPOSE: We provide insight into the presentation, diagnostics, treatment, and
      accompanying clinical difficulties and complications of an arterio-ureteral
      fistula and add 11 patients with arterio-ureteral fistula to the 90 described in
      the literature. MATERIALS AND METHODS: A retrospective search was done for
      confirmed cases of arterio-ureteral fistula that were treated at 3 medical
      centers. RESULTS: A total of 11 cases of arterio-ureteral fistula were reviewed
      from 1980 to 2006. A history of major abdominal surgery had an essential role in
      10 of the 11 cases, especially vascular intervention in 8. All patients presented
      with varying manifestations of hematuria. Ureteral contrast studies and
      nonprovocative angiography provided the most valuable diagnostic information with
      all 5 and 3 of 5 showing positive results, respectively. In 4 of 11 patients
      (36%) the diagnosis of arterio-ureteral fistula was only made during laparotomy.
      Ten patients were treated with a classic open surgical approach (vascular and
      urological) and in 1 endovascular stents were inserted. Two of 11 patients (18%)
      needed acute surgical intervention because of hemodynamic instability. The in
      hospital mortality rate was 9%. At a mean followup of 17 months 3 other patients
      (27%) had died of causes unrelated to the arterio-ureteral fistula. CONCLUSIONS:
      The diagnosis of arterio-ureteral fistula should be considered in patients with
      persistent hematuria who have a history of major abdominal vascular surgery even
      when diagnostic test results are negative for a fistula, because in 36% of our
      patients the diagnosis could only be made at operation. The in hospital morbidity
      and mortality rates are considerable and, therefore, a timely diagnosis and
      elective multidisciplinary treatment are preferred.

PMID- 18078960
TI  - Treatment with insulin inhibits poly(ADP-ribose)polymerase activation in a rat
      model of endotoxemia.
AB  - In critically ill patients various conditions may lead to the activation of
      poly(ADP-ribose) polymerase (PARP). By promoting cellular energetic dysfunction,
      and by enhancing pro-inflammatory gene expression, PARP activation significantly
      contributes to the pathogenesis of shock. PARP activation is usually triggered by
      DNA strand breakage, which is typically the result of the overproduction of
      various reactive oxidant species. One of the pathophysiological conditions
      associated with PARP activation is hyperglycemia, where the reactive species are
      produced from the mitochondria and other cellular sources. In the present study
      we tested whether endotoxin-induced PARP activation and pro-inflammatory mediator
      production can be modified by insulin therapy. Rats subjected to bacterial
      lipopolysaccharide (LPS) with or without insulin co-treatment were studied. LPS
      induced PARP activation in circulating lymphocytes was measured by flow
      cytometry, tumor necrosis factor alpha (TNF-alpha) production was measured by
      ELISA. The direct effect of insulin on the PARP activity of mononuclear
      leukocytes and human umbilical vein endothelial cells (HUVEC) in elevated glucose
      conditions was tested in vitro. LPS-induced significant hyperglycemic response
      activated PARP in circulating lymphocytes and induced TNF-alpha production.
      Insulin treatment prevented LPS-induced hyperglycemic response, blocked PARP
      activation and blunted LPS-induced TNF-alpha response. Insulin treatment caused a
      slight reduction in the PARP activity of mononuclear cells and HUVECs in vitro.
      We demonstrate that insulin treatment blocks LPS-induced PARP activation in vivo.
      We propose that this effect is mainly indirect, and occurs due to the prevention
      of stress induced hyperglycemia, with a direct cellular effect of insulin playing
      a potential minor supplemental role. The current findings may have significant
      implications in the context of the emerging concept of tight glycemic control and
      insulin treatment for critically ill patients.

PMID- 18078961
TI  - Field application of a method for measuring DNA damage in polychaete blood cells
      exposed to Masan Bay sediment extracts.

PMID- 18078962
TI  - Folic acid administration produces an antidepressant-like effect in mice:
      evidence for the involvement of the serotonergic and noradrenergic systems.
AB  - Clinical studies have shown that folic acid plays a role in the pathophysiology
      of depression. However, very few studies have investigated its effect in
      behavioral models of depression. Hence, this study tested its effect in the
      forced swimming test (FST) and the tail suspension test (TST), two models
      predictive of antidepressant activity, in mice. Folic acid administered by oral
      route (p.o.) produced a reduction in the immobility time in the FST (50-100mg/kg)
      and in the TST (10-50mg/kg). The administration of folic acid by i.c.v. route
      also reduced the immobility time in the FST (10nmol/site) and in the TST (1
      10nmol/site). Both folic acid administered by oral and i.c.v. route produced no
      psychostimulant effect, which indicates that its antidepressant-like effect is
      specific. Pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA;
      100mg/kg, i.p., an inhibitor of serotonin (5-HT) synthesis, for 4 consecutive
      days), ketanserin (5mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), prazosin
      (1mg/kg, i.p., an alpha(1)-adrenoceptor antagonist) or yohimbine (1mg/kg, i.p.,
      an alpha(2)-adrenoceptor antagonist) prevented the anti-immobility effect of
      folic acid (50mg/kg, p.o.) in the FST. Moreover, the pretreatment of mice with
      WAY100635 (0.1mg/kg, s.c., a selective 5-HT(1A) receptor antagonist) blocked the
      decrease in immobility time in the FST elicited by folic acid (50mg/kg, p.o.),
      but produced a synergistic effect with a subeffective dose of folic acid
      (10mg/kg, p.o.). In addition, a subeffective dose of folic acid (10mg/kg, p.o.)
      produced a synergistic antidepressant-like effect with fluoxetine (10mg/kg, p.o.)
      in the FST. Overall, the results firstly indicate that folic acid produced an
      antidepressant-like effect in FST and in TST and that this effect appears to be
      mediated by an interaction with the serotonergic (5-HT(1A) and 5-HT(2A/2C)
      receptors) and noradrenergic (alpha(1)- and alpha(2)-adrenoceptors) systems.

PMID- 18078963
TI  - Heterogeneity of nicotinic acetylcholine receptor expression in the caudal
      nucleus of the solitary tract.
AB  - The nucleus of the solitary tract (NTS) is the principal integrating relay in the
      processing of visceral sensory and gustatory information. In the present study,
      patch-clamp electrophysiological experiments were conducted using rat horizontal
      brainstem sections. Pre-synaptic and somatic/dendritic nicotinic acetylcholine
      receptors (nAChRs) expressed in neurons of the caudal NTS (cNTS) were found to be
      randomly distributed between pre-synaptic and somatic/dendritic sites
      (chi(2)=0.72, df=3, p>0.87, n=200). Pre-synaptic nAChRs were detected by their
      facilitating effects on glutamatergic neurotransmission of a sub-population of
      cNTS neurons (categorized as "effect-positive") upon brief picospritzer
      applications of 0.1-0.5mM nicotine. These effects were resistant to inhibition by
      20nM methyllycaconitine (MLA) and 4muM dihydro-beta-erythroidine (DHbetaE), and
      were replicated by brief picospritzer applications of 0.2-1mM cytisine.
      Picospritzer applications of 0.2mM RJR-2403, a potent agonist of alpha4beta2
      nAChRs, did not facilitate synaptic release of glutamate in effect-positive cNTS
      neurons. The population of somatic/dendritic nAChRs has been found to be
      heterogeneous and included nAChRs that were activated by RJR-2403 and/or
      cytisine, or insensitive to cytisine, or inhibited by MLA. The presented results
      are consistent with the expression of beta4-containing (i.e., beta4*) nAChRs,
      likely alpha3beta4*, in pre-synaptic terminals of effect-positive cNTS neurons.
      Somatic/dendritic nAChRs appear to involve both alpha7 and non-alpha7 subunits.
      Heterogeneity in the subunit composition of pre-synaptic and somatic/dendritic
      nAChRs may underlie diverse roles that these receptors play in regulation of
      behavioral and visceral reflexes, and may reflect specific targeting by
      endogenous nicotinic agents and nicotine.

PMID- 18078964
TI  - The aspirin metabolite salicylate enhances neuronal excitation in rat hippocampal
      CA1 area through reducing GABAergic inhibition.
AB  - Salicylate is the major metabolite and active component of aspirin
      (acetylsalicylic acid), which is widely used in clinical medicine for treating
      inflammation, pain syndromes and cardiovascular disorders. The well-known
      mechanism underlying salicylate's action mainly involves the inhibition of
      cyclooxygenase and subsequent decrease in prostaglandin production. Recent
      evidence suggests that salicylate also affects neuronal function through
      interaction with specific membrane channels/receptors. However, the effect of
      salicylate on synaptic and neural network function remains largely unknown. In
      this study, we investigated the effect of sodium salicylate on the synaptic
      transmission and neuronal excitation in the hippocampal CA1 area of rats, a key
      structure for many complex brain functions. With electrophysiological recordings
      in hippocampal slices, we found that sodium salicylate significantly enhanced
      neuronal excitation through reducing inhibitory GABAergic transmission without
      affecting the basal excitatory synaptic transmission. Salicylate significantly
      inhibited the amplitudes of both evoked and miniature inhibitory postsynaptic
      currents, and directly reduced gamma-aminobutyric acid type A (GABA(A)) receptor
      mediated responses in cultured rat hippocampal neurons. Together, our results
      suggest that the widely used aspirin might impair hippocampal synaptic and neural
      network functions through its actions on GABAergic neurotransmission. Given the
      capability of aspirin to penetrate the blood-brain barrier, the present data
      imply that aspirin intake may cause network hyperactivity and be potentially
      harmful in susceptible subpopulations.

PMID- 18078965
TI  - Phytoalexins and phytoanticipins from the wild crucifers Thellungiella halophila
      and Arabidopsis thaliana: rapalexin A, wasalexins and camalexin.
AB  - Investigation of phytoalexin production using abiotic elicitation showed that the
      phytoalexin rapalexin A was produced by both Thellungiella halophila and
      Arabidopsis thaliana, but while A. thaliana produced camalexin, T. halophila
      produced wasalexins A and B and methoxybrassenin B. Considering that the genome
      of T. halophila is being sequenced currently and that the wasalexin pathway
      present in T. halophila is expected to involve a number of genes also present in
      Brassica species, our discovery should facilitate the isolation of genes involved
      in biosynthetic pathways of phytoalexins of the most economically important
      crucifer species.

PMID- 18078966
TI  - People, policy and public health.

PMID- 18078967
TI  - Rats fed soy protein isolate (SPI) have impaired hepatic CYP1A1 induction by
      polycyclic aromatic hydrocarbons as a result of interference with aryl
      hydrocarbon receptor signaling.
AB  - Consumption of soy diets has been found to reduce cancer incidence in animals and
      is associated with reduced cancer risk in humans. Previously, we have
      demonstrated that female Sprague-Dawley rats fed purified AIN-93G diets with soy
      protein isolate (SPI) as the sole protein source had reduced CYP1A1 induction and
      basal aryl hydrocarbon receptor (AhR) levels relative to those fed the same diet
      containing casein (CAS). In the present study, the molecular mechanisms
      underlying reduced AhR expression have been studied. The SPI-effect on AhR was
      not observed after feeding diets containing the purified soy isoflavones
      genistein or daidzein. Rat hepatoma FGC-4 cells were treated with the serum
      obtained from rats fed CAS- or SPI-containing diets. Reduced AhR levels (P<0.05)
      were observed after 24 h exposure to SPI-serum without any changes in the overall
      expression of chaperone proteins--HSP90 and XAP2. SPI-serum-stimulated AhR
      degradation was inhibited by treating the cells with the proteasome inhibitor,
      MG132, and was observed to be preceded by ubiquitination of the receptor. A
      reduced association of XAP2 with the immunoprecipitated AhR complex was observed.
      SPI-serum-mediated AhR degradation was preceded by nuclear translocation of the
      receptor. However, the translocated receptor was found to be unable to
      heterodimerize with ARNT or to bind to XRE elements on the CYP1A1 enhancer. These
      data suggest that feeding SPI-containing diets antagonizes AhR signaling by a
      novel mechanism which differs from those established for known AhR antagonists.

PMID- 18078968
TI  - Inhibition of c-Jun N-terminal kinase sensitizes tumor cells to flavonoid-induced
      apoptosis through down-regulation of JunD.
AB  - Reduction of susceptibility to apoptosis signals is a crucial step in
      carcinogenesis. Therefore, sensitization of tumor cells to apoptosis is a
      promising therapeutic strategy. c-Jun NH2-terminal kinase (JNK) has been
      implicated in stress-induced apoptosis. However, many studies also emphasize the
      role of JNK on cell survival, although its mechanisms are not completely
      understood. Previously, we found that inhibition of JNK activity promotes
      flavonoid-mediated apoptosis of human osteosarcoma cells. We thus determined
      whether inhibition of JNK sensitizes tumor cells to a bioflavonoid-induced
      apoptosis, and whether this effect of JNK is a general effect. As the results,
      quercetin and genistein as well as a flavonoid fraction induced apoptosis of
      tumor cells, which was further accelerated by specific JNK inhibitor, SP600125 or
      by small interfering RNA specific to JNK1/2. This effect was specific to types of
      cells because it was further apparent in tumorigenic cell lines. Inhibition of
      JNK by SP600125 also reduced flavonoid-stimulated nuclear induction of JunD which
      was known to have protective role in apoptosis, whereas JNK inhibition alone had
      little effect on apoptosis. The flavonoid-induced apoptosis of tumor cells was
      significantly enhanced by transfecting them with antisense JunD oligonucleotides.
      These results suggest that inhibition of JNK facilitates flavonoid-induced
      apoptosis through down-regulation of JunD, which is further sensitive to tumor
      cells. Therefore, combination with a specific JNK inhibitor further enhances the
      anti-cancer and chemopreventive potential of bio-flavonoids.

PMID- 18078969
TI  - In vitro expression of hard metal dust (WC-Co)--responsive genes in human
      peripheral blood mononucleated cells.
AB  - Hard metals consist of tungsten carbide (WC) and metallic cobalt (Co) particles
      and are important industrial materials produced for their extreme hardness and
      high wear resistance properties. While occupational exposure to metallic Co alone
      is apparently not associated with an increased risk of cancer, the WC-Co particle
      mixture was shown to be carcinogenic in exposed workers. The in vitro
      mutagenic/apoptogenic potential of WC-Co in human peripheral blood mononucleated
      cells was previously demonstrated by us. This study aimed at obtaining a broader
      view of the pathways responsible for WC-Co induced carcinogenicity, and in
      particular genotoxicity and apoptosis. We analyzed the profile of gene expression
      induced in vitro by WC-Co versus control (24 h treatment) in human PBMC and
      monocytes using microarrays. The most significantly up-regulated pathways for WC
      Co treated PBMC were apoptosis and stress/defense response; the most down
      regulated was immune response. For WC-Co treated monocytes the most significantly
      up- and down-regulated pathways were nucleosome/chromatin assembly and immune
      response respectively. Quantitative RT-PCR data for a selection of the most
      strongly modulated genes (HMOX1, HSPA1A, HSPA1L, BNIP3, BNIP3L, ADORA2B, MT3,
      PLA2G7, TNFAIP6), and some additionally chosen apoptosis related genes (BCL2,
      BAX, FAS, FASL, TNFalpha), confirmed the microarray data after WC-Co exposure and
      demonstrated limited differences between the Co-containing compounds. Overall,
      this study provides the first analysis of gene expression induced by the WC-Co
      mixture showing a large profile of gene modulation and giving a preliminary
      indication for a hypoxia mimicking environment induced by WC-Co exposure.

PMID- 18078970
TI  - In vivo immunomodulatory effects of Antrodia camphorata polysaccharides in a
      T1/T2 doubly transgenic mouse model for inhibiting infection of Schistosoma
      mansoni.
AB  - Antrodia camphorata (A. camphorata) is a fungus commonly used for treatment of
      viral hepatitis and cancer in Chinese folk medicine. Extract of A. camphorate is
      reported to possess anti-inflammatory, antihepatitis B virus and anticancer
      activities. In this study, we tested the in vivo effects of polysaccharides
      derived from A. camphorata (AC-PS) on immune function by detection of cytokine
      expression and evaluation of the immune phenotype in a T1/T2 doubly transgenic
      mouse model. The protective effect of AC-PS in mice was tested by infection with
      Schistosoma mansoni. The induction of large amounts of IFN-gamma, IL-2 and TNF
      alpha mRNA were detected after 2 and 4 weeks of oral AC-PS administration in
      BALB/c and C57BL/6 mice. In transgenic mice, 3 to 6 weeks of oral AC-PS
      administration increased the proportion of CD4(+) T cells and B cells within the
      spleen. More specifically, there was an increase of Th1 CD4(+) T cells and Be1
      cells among spleen cells as observed by detection the of Type1/Type2 marker
      molecules. By using a disease model of parasitic infection, we found that AC-PS
      treatment inhibited infection with S. mansoni in BALB/C and C57BL/6 mice. AC-PS
      appears to influence the immune system of mice into developing Th1 responses and
      have potential for preventing infection with S. mansoni.

PMID- 18078971
TI  - Teratogenicity of Mimosa tenuiflora seeds to pregnant rats.
AB  - Bone and other malformations caused by the ingestion of Mimosa tenuiflora are
      common in ruminants in the Brazilian semiarid. The aim of this research was to
      study the teratogenic effects of M. tenuiflora in Wistar rats (Rattus
      novergicus). The experimental group had 15 females and was fed, from the 6th to
      the 21st day of pregnancy, with a ration containing 10% of M. tenuiflora seeds.
      The control group, with 10 females, was fed with the same ration without seeds.
      There were no differences in weight gains, and food and water consumption between
      treated and control rats. Ninety bone malformations were observed in 40 of the
      101 fetuses born in the experimental group, and four malformations were observed
      in three of the 58 fetuses born in the control group (p<0.05). The weight and
      number of ossification centers of the fetuses from the experimental group were
      higher than those from the control group (p<0.05). It is concluded that the seeds
      of M. tenuiflora are teratogenic to rat fetuses.

PMID- 18078972
TI  - Normalized split-spectrum: a detection approach.
AB  - We consider in this paper the problem of automatic detection of ultrasonic echo
      pulses in a grain noise background. We start by assuming a reference model for
      grain noise: multivariate correlated Gaussian model having, in general, different
      variances under every hypothesis. We show that, even for this simple model, there
      is not practical optimum solution, except if the variances are equal under every
      hypothesis and the echo pulse satisfies a spectral constraint. Then we consider
      split-spectrum (SS) suboptimum solutions. Firstly, SS algorithms are formulated
      following an algebraic approach which is appropriate in an automatic detection
      framework. Popular minimization and polarity thresholding algorithms are
      considered under this framework. Then a new detector called normalized SS (NSS)
      is proposed. The underlying idea is to actually exploit the tuning frequency
      sensitivity (i.e., variability of the output magnitudes from one SS channel to
      another), making this measurement independent of the absolute magnitudes.
      Different experiments with simulated and real data show evidences of the interest
      of the new method in an automatic detection framework. Derivations of the
      formulas for fitting the probability of false alarm in every detector are
      included in the paper.

PMID- 18078973
TI  - The lactococcal abortive infection protein AbiP is membrane-anchored and binds
      nucleic acids.
AB  - AbiP, a lactococcal abortive phage infection system, has previously been shown to
      arrest phage bIL66M1 DNA replication around 10 min after infection and to inhibit
      the switch off of phage early transcripts. We report here the functional
      characterization and implication in the abortive infection phenotype of two
      domains identified in the AbiP sequence. We show that AbiP is a protein anchored
      to the membrane by an N-terminal membrane-spanning domain. Our results further
      suggest that membrane localization may be required for the anti-phage activity of
      AbiP. The remainder of the protein, which contains a putative nucleic acid
      binding domain, is shown to be located on the cytosolic side. Purified AbiP is
      shown to bind nucleic acids with an approximately 10-fold preference for RNA
      relative to ssDNA. AbiP interaction with both ssDNA and RNA molecules occurs in a
      sequence-independent manner. We have analyzed the effect of substitutions of
      aromatic and basic residues on the surface of the putative binding fold. In vitro
      and in vivo studies of these AbiP derivatives indicate that the previously
      reported effects on phage development might be dependent on the nucleic acid
      binding activity displayed by the membrane-bound protein.

PMID- 18078974
TI  - Complex effects of foamy virus central purine-rich regions on viral replication.
AB  - Similar to the lentiviruses family of retroviruses, foamy viruses (FVs) contain
      purine-rich sequences located in the center of the genome. Their function on
      viral replication or vector transfer remains elusive, although dual initiation of
      plus-strand reverse transcription has been suggested. To elucidate the physical
      nature of the central region of the prototype FV (PFV) genome, we performed 3'
      and 5' RACE experiments. Our results revealed that the PFV genome contains a
      centrally located gap in the DNA plus-strand with no definite termination and
      start point and of variable length. We did not find evidence for a DNA flap
      region. The PFV isolate harbors four centrally located purine-rich elements (A
      D). Only the D element is identical in sequence to the 3' poly purine tract
      (PPT). We mutated these elements while conserving or altering the overlapping pol
      reading frame and analyzed the mutants for transient replication in an infectious
      or for vector transfer in a replication-deficient background. In addition, we
      determined the protein composition of the respective viral particles. The A and B
      elements appeared to play a role in Pol protein encapsidation, the C element is
      likely involved in regulating gene expression, while mutation of the D element
      resulted in an insignificant reduction in transiently replicating virus and an
      approximately 50% reduction in vector titer. The reason for this deficit remains
      to be elucidated.

PMID- 18078976
TI  - Differential detection of global luminance and contrast changes across saccades
      and flickers during active scene perception.
AB  - How sensitive are viewers to changes in global image properties across saccades
      during active real-world scene perception? This question was investigated by
      globally increasing and/or decreasing luminance or contrast in photographs of
      real-world scenes across saccadic eye movements or during matched brief
      interruptions in a flicker paradigm. The results from two experiments
      demonstrated very poor sensitivity to global image changes in both the saccade
      contingent and flicker paradigms, suggesting that the specific values of basic
      sensory properties do not contribute to the perception of stability across
      saccades during complex scene perception. In addition, overall sensitivity was
      significantly worse in the saccade-contingent change paradigm than the flicker
      paradigm, suggesting that the flicker paradigm is an imperfect simulation of
      transsaccadic vision.

PMID- 18078975
TI  - Retinotopy of the face aftereffect.
AB  - Physiological results for the size of face-specific units in inferotemporal
      cortex (IT) support an extraordinarily large range of possible sizes--from 2.5
      degrees to 30 degrees or more. We use a behavioral test of face-specific
      aftereffects to measure the face analysis regions and find a coarse retinotopy
      consistent with receptive fields of intermediate size (10 degrees -12 degrees at
      3 degrees eccentricity). In the first experiment, observers were adapted to a
      single face at 3 degrees from fixation. A test (a morph of the face and its anti
      face) was then presented at different locations around fixation and subjects
      classified it as face or anti-face. The face aftereffect (FAE) was not constant
      at all test locations--it dropped to half its maximum value for tests 5 degrees
      from the adapting location. Simultaneous adaptation to both a face and its anti
      face, placed at opposite locations across fixation, produced two separate regions
      of opposite aftereffects. However, with four stimuli, faces alternating with anti
      faces equally spaced around fixation, the FAE was greatly reduced at all
      locations, implying a fairly coarse localization of the aftereffect. In the
      second experiment, observers adapted to a face and its anti-face presented either
      simultaneously or in alternation. Results showed that the simultaneous
      presentation of a face and its anti-face leads to stronger FAEs than sequential
      presentation, suggesting that face processing has a dynamic nature and its region
      of analysis is sharpened when there is more than one face in the scene. In the
      final experiment, a face and two anti-face flankers with different spatial
      offsets were presented during adaptation and the FAE was measured at the face
      location. Results showed that FAE at the face location was inhibited more as the
      distance of anti-face flankers to the face stimulus was reduced. This confirms
      the spatial extent of face analysis regions in a test with a fixed number of
      stimuli where only distance varied.

PMID- 18078977
TI  - Evaluation of copper effects upon Girardia tigrina freshwater planarians based on
      a set of biomarkers.
AB  - Copper is a common environmental contaminant, which is particularly toxic to
      living organisms when in high concentrations. To monitor environmental
      contamination by Cu2+ and other heavy metals, well characterized bioindicator
      organisms and standardized assays are needed. As a first step toward this end, we
      have analysed Cu2+ effects upon Girardia tigrina freshwater planarians, based on
      the assessment of mobility, regeneration performance, micronucleus (MN) frequency
      in regenerating animals, and reproductive performance. These four biomarkers
      provided complementary information on Cu2+ toxicity, teratogenicity, mutagenicity
      and chronic (>96 h of exposure) effects, respectively. The LC50 was calculated
      for newborn, adult and regenerating planarians, and values of 12+/-0.02 mg l(-1),
      42+/-0.08 mg l(-1), 48+/-0.13 mg l(-1), respectively, were obtained after 96 h of
      exposure. Mobility, for intact adults, and time of regeneration and MN frequency,
      for regenerating animals, were significantly affected by Cu2+ concentrations as
      low as 0.10 mg l(-1). MN assay for regenerating G. tigrina neoblasts showed
      higher sensitivities than MN assays performed with other bioindicator freshwater
      organisms, such as moluscs or fish. Chronic exposure effects were clearly
      evidenced by assessment of reproductive performance, with significant reduction
      in fecundity and fertility rates upon exposure to Cu2+ concentrations as low as
      0.05 mg l(-1). Therefore, G. tigrina can be regarded as a useful bioindicator
      species for the detection and evaluation of Cu2+ effects upon freshwater
      invertebrates, allowing insights on the effects of Cu2+ (and possibly other heavy
      metals) in a freshwater environment.

PMID- 18078978
TI  - Determination of major natural and anthropogenic source profiles for particulate
      matter and trace elements in Izmir, Turkey.
AB  - Samples of PM10 and PM2.5 were collected from several natural and anthropogenic
      sources using in-stack cyclone, grab sampling/resuspension chamber and ambient
      air samplers. The chemical characterization of the samples was achieved
      containing Al, Ba, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Sr, V and Zn using
      an inductively coupled plasma-optical emission spectrometer (ICP-OES). The
      elemental fractions (weight percent by mass), standard deviations and
      uncertainties were reported. The elemental compositions of PM emitted from
      mineral industries and cement kiln were dominated by terrestrial elements,
      particularly Ca, whereas the profile of top-soil mainly contained Al and Ca. The
      profiles of industrial sources were generally typical for related ones; however,
      significant differences were obtained for some of them. Similarly, the profiles
      of fuel burning emissions have significant differences compared to profiles
      obtained all around the world.

PMID- 18078979
TI  - PCDD/Fs and DL-PCBs in feeding fats obtained as co-products or by-products
      derived from the food chain.
AB  - Among the tasks included in the "Quality and safety of feeding fats obtained from
      co-products or by-products of the food chain" Project, supported by the European
      Union and included in the 6th Framework Program, a number of fats and oils
      collected as co- or by-products from the food chain were selected for the
      determination of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs) and 'dioxin-like' polychlorinated biphenyls (DL-PCBs). In
      the majority of the cases these samples are currently employed as feed
      ingredients. Nevertheless, additional fats, which are forbidden for feedstuff
      purposes were also considered in this study. In general terms, fats and oils were
      classified taking into account their nature and the processes applied to obtain
      these co- or by-products. PCDD/F and DL-PCB levels were evaluated in a first
      group of samples composed of fish oils, animal fats and lecithins. As expected,
      fats and oils with an animal origin presented higher concentrations, expressed in
      pg WHO-TEQ/g, compared to the levels found in vegetable samples like lecithins.
      The category of fish oils had the highest values for both PCDD/Fs and the sum of
      PCDD/Fs and DL-PCBs, with some samples showing levels above the maximum
      established at the present legislation related to the presence of PCDD/Fs and DL
      PCBs in animal feed [Commission Directive 2006/13/EC of 3 February 2006 amending
      Annexes I and II to Directive 2002/32/EC of the European Parliament and of the
      Council on undesirable substances in animal feed as regards dioxins and dioxin
      like PCBs. Official Journal of the European Communities L32, 44-53]. In a second
      group, fats and oils with a more complex composition obtained from different
      transformation processes or even mixtures of fats were considered; thus, acid
      oils from chemical refining, acid oils from physical refining, recycled cooking
      oils, oils extracted from exhausted bleaching earths, hydrogenated by-products,
      fatty acids calcium soaps and miscellaneous fats were analyzed. The data revealed
      a significant variability in PCDD/F and DL-PCB levels, expressed in pg WHO-TEQ/g,
      in these products. It has to be pointed out that the analyses of fats and oils
      belonging to these categories of products were sometimes difficult due to the
      complexity of the samples. In terms of legislation most of these samples cannot
      be easily included into one of the specific categories of substances intended for
      feedstuff purposes that are regulated in Commission Directive 2006/13/EC.

PMID- 18078980
TI  - Acetochlor mineralization and fate of its two major metabolites in two soils
      under laboratory conditions.
AB  - The degradation of the herbicide acetochlor, in a neoluvisol and in a calcosol
      were studied as a function of depth (0-25cm and 25-50cm) and temperature (25
      degrees C and 15 degrees C) under controlled laboratory conditions during 58 and
      90 days, respectively. The surface and sub-surface soil samples were respectively
      spiked with 1 and 0.01mgkg(-1) of 14C-acetochlor, the concentrations observed in
      previous field monitoring. The half-lives (DT50) varied from 1.4 to 14.9 days
      depending on the soil, temperature and applied concentration. The maximal
      mineralization (24%) was observed for the surface calcosol at 25 degrees C. The
      comparison of results obtained for sterilized and non-sterilized soils, the
      decrease of DT50 with the increase of temperature, the shape of CO2 emissions and
      the increase of number of aerobic endogenous microflora through the experiment
      suggested that biological process are dominant in degradation. A particular
      attention was paid to the formation and dissipation of metabolites ESA
      (ethanesulphonic acid) and OA (oxanilic acid) during the whole experiment. At 25
      degrees C, ESA and OA were observed after three days, but as ESA concentration
      decreased over time in surface calcosol, it remained constant in surface
      neoluvisol. A difference in ESA/OA ratio depends on the soil with a predominance
      of OA in surface neoluvisol and a disappearance of OA in surface calcosol.

PMID- 18078981
TI  - Physical activity in patients with deep venous thrombosis: a systematic review.
AB  - OBJECTIVES: We performed a systematic review to assess the benefits or risks of
      physical activity in patients with an acute or previous DVT of the leg. DATA
      SOURCES: PubMed, EMBASE and Science Citation Index were searched without language
      restrictions up to July 2007. Bibliographies of retrieved articles and personal
      files were also searched. REVIEW METHODS: Randomized trials and prospective
      cohort studies that included patients with acute or previous DVT, described an
      exercise intervention or exercise exposure, and described any related clinical
      outcome were selected. Data were independently extracted by 2 investigators.
      RESULTS: Seven randomized trials and two prospective observational studies were
      included. Early exercise, compared with bed rest, was associated with a similar
      short-term risk of pulmonary embolism in patients with acute DVT and led to more
      rapid resolution of limb pain. In patients with acute DVT, a 6 month daily
      walking program led to similar degrees of vein recanalization and improvement in
      quality of life as controls. In patients with previous DVT, 30 min of vigorous
      treadmill exercise did not worsen venous symptoms and improved calf muscle
      flexibility; a 6 month exercise training program improved calf muscle strength
      and pump function; and high levels of physical activity at one month tended to be
      associated with reduced severity of postthrombotic symptoms during the subsequent
      3 months. CONCLUSIONS: Early walking exercise is safe in patients with acute DVT
      and may help to reduce acute symptoms. Exercise training does not increase leg
      symptoms acutely in patients with a previous DVT and may help to prevent or
      improve the postthrombotic syndrome.

PMID- 18078982
TI  - Diagnostic challenges in extrauterine epithelioid trophoblastic tumours: a report
      of two cases.
AB  - INTRODUCTION: Epithelioid trophoblastic tumour (ETT) is a rare condition with a
      paucity of cases reported in the literature. CASE REPORTS: We present two unusual
      cases of ETT. Both patients presented with markedly elevated hCG levels; one case
      presented with a mass in the gallbladder, the other with extensive metastases;
      and both patients died from disease. DISCUSSION: To gain a greater understanding
      of the nature and progression of this disease, reporting of cases in the
      literature should be thorough and contain detailed information on patient
      clinicopathological characteristics and treatment. To enable identification of
      prognostic factors, long-term follow up must also be reported because recurrence
      can be both late and complex.

PMID- 18078985
TI  - The effects of physical activity counseling on mood among 75- to 81-year-old
      people: a randomized controlled trial.
AB  - OBJECTIVES: To examine the effects of physical activity counseling on mood among
      older people unselected for their depressive symptomatology. METHODS: Data are
      from "Screening and Counseling for Physical Activity and Mobility in Older
      People" project (SCAMOB), conducted in Finland during 2003-2005. SCAMOB was a 2
      year single-blinded randomized controlled trial among 624 participants 75 years
      and older randomized into physical activity counseling group and control group.
      Depressive symptoms were assessed at baseline and after 24 months using Center
      for the Epidemiologic Studies Depression Scale. RESULTS: Among all the study
      participants, no effect of intervention was observed. However, among subgroup
      with minor depressive symptoms at baseline, a significant treatment effect was
      observed, where depressive symptoms decreased in the intervention group and
      increased in the control group. CONCLUSIONS: These findings suggest that physical
      activity counseling may reduce depression among those with minor depressive
      symptoms, which warrants for future studies.

PMID- 18078986
TI  - Efficient intracellular delivery of functional proteins using cationic polymer
      core/shell nanoparticles.
AB  - Cationic core/shell nanoparticles self-assembled from biodegradable, cationic and
      amphiphilic copolymer poly{N-methyldietheneamine sebacate)-co-[(cholesteryl
      oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate}, P(MDS
      co-CES), were fabricated and employed to deliver lectin A-chain, an anticancer
      glycoprotein. Lectin A-chain was efficiently bound onto the surfaces of the
      nanoparticles at high mass ratios of nanoparticles to lectin A-chain. The
      nanoparticle/lectin A-chain complexes had an average size of approximately 150 nm
      with zeta potential of about +30 mV at the mass ratio of 50 or above while the
      BioPorter/lectin A-chain complexes had a larger particle size and relatively
      lower zeta potential (150 nm vs. 455 nm; +30 mV vs. +20 mV). Therefore, the
      cellular uptake of nanoparticle/lectin A-chain complexes was much greater than
      that of BioPorter/lectin A-chain complexes. The results obtained from
      cytotoxicity tests show that lectin A-chain delivered by the nanoparticles was
      significantly more toxic against MDA-MB-231, HeLa, HepG2 and 4T1 cell lines when
      compared to BioPorter, and IC50 of lectin A-chain delivered by the nanoparticles
      was 0.2, 0.5, 10 and 50 mg/l, respectively, while that of lectin A-chain
      delivered by BioPorter was higher than 100 mg/l in all cell lines tested. These
      nano-sized particles may provide an efficient approach for intracellular delivery
      of biologically active proteins.

PMID- 18078987
TI  - Efficient and stable gene transfer of growth factors into chondrogenic cells and
      primary articular chondrocytes using a VSV.G pseudotyped retroviral vector.
AB  - Since efficient transfer of foreign genes into primary articular chondrocytes
      (CC) is difficult, a VSV.G pseudotyped retroviral vector (Bullet) was developed
      for marker and growth factor gene transfer. Transduction efficiency was analysed
      by FACS. BMP2 production was determined by specific hBMP2-ELISA. BMP2 effect on
      cells regarding proteoglycan production was measured by alcian blue staining and
      dye quantification. Alkaline phosphatase activity was determined by enzymatic
      reaction with p-nitrophenyl phosphate at OD 405nm and proliferation rate was
      analysed by MTT-assay. ATDC5 cells (98.3+/-0.6%SD) were transduced to express the
      reporter gene eGFP. After 52 weeks 94.7+/-0.6%SD of cells were positive.
      Retroviral transduction efficiency for nlslacZ exceeded 92.3+/-6.1%SD in rabbit
      CC and expression remained high after 15 weeks (75.7+/-14.2%SD). ATDC5 cells and
      CC expressed the growth factor gene hBMP2 after retroviral transduction at
      different time-points. BMP2 led to an increase in proteoglycan and alkaline
      phosphatase production. Initially, the proliferation rate detected by MTT-assay
      increased in both the cell types; afterwards the proliferation rate was similar
      to controls. The described retroviral vector system achieved high initial
      transduction rates in ATDC5 cells and CC. Gene transfer was very stable over the
      time period analysed, rendering it a useful tool for future in vitro and in vivo
      studies on cartilage remodelling.

PMID- 18078984
TI  - Uncovering the mechanisms of estrogen effects on hippocampal function.
AB  - Estrogens have direct effects on the brain areas controlling cognition. One of
      the most studied of these regions is the dorsal hippocampal formation, which
      governs the formation of spatial and episodic memories. In laboratory animals,
      most investigators report that estrogen enhances synaptic plasticity and improves
      performance on hippocampal-dependent cognitive behaviors. This review summarizes
      work conducted in our laboratory and others toward identifying estrogen's actions
      in the hippocampal formation, and the mechanisms for these actions. Physiologic
      and pharmacologic estrogen affects cognitive behavior in mammals, which may be
      applicable to human health and disease. The effects of estrogen in the
      hippocampal formation that lead to modulation of hippocampal function include
      effects on cell morphology, synapse formation, signaling, and excitability that
      have been studied in laboratory mice, rats, and primates. Finally, estrogen may
      signal through both nuclear and extranuclear hippocampal estrogen receptors to
      achieve its downstream effects.

PMID- 18078988
TI  - The effect of electronegativity and angiotensin-converting enzyme inhibition on
      the kinin-forming capacity of polyacrylonitrile dialysis membranes.
AB  - The combination of negatively-charged membranes and angiotensin I-converting
      enzyme inhibitors (ACEi) evokes hypersensitivity reactions (HSR) during
      hemodialysis and bradykinin (BK)-related peptides have been hypothesized as being
      responsible for these complications. In this study, we tested the effects of
      neutralizing the membrane electronegativity (zeta potential) of polyacrylonitrile
      AN69 membranes by coating a polyethyleneimine layer (AN69-ST membranes) over the
      generation of kinins induced by blood contact with synthetic membranes. We used
      minidialyzers with AN69 or AN69-ST membranes in an ex vivo model of plasma and we
      showed that plasma dialysis with AN69 membranes led to significant BK and des
      Arg(9)-BK release, which was potentiated by ACEi. This kinin formation was
      dramatically decreased by AN69-ST membranes, even in the presence of an ACEi, and
      kinin recovery in the dialysates was also significantly lower with these
      membranes. High molecular weight kininogen and factor XII detection by
      immunoblotting of the protein layer coating both membranes corroborated the
      results: binding of these proteins and contact system activation on AN69-ST
      membranes were reduced. This ex vivo experimental model applied to the plasma,
      dialysate and dialysis membrane could be used for the characterization of the
      kinin-forming capacity of any biomaterial potentially used in vivo in combination
      with drugs which modulate the pharmacological activity of kinins.

PMID- 18078989
TI  - DC-sign+ CD163+ macrophages expressing hyaluronan receptor LYVE-1 are located
      within chorion villi of the placenta.
AB  - The purpose of this study was to investigate with immunohistochemical methods
      antigen presenting cells and their relationship to blood and lymphatic vessels in
      human term placenta. Fetal placental antigen presenting cells, historically also
      known as Hofbauer cells, were located in the chorionic villi below the
      syncytiotrophoblast and in the vicinity of fetal capillaries. DC-SIGN/CD209
      expression was observed on CD163+, CD68+, CD45+, HLA-A,B,C+, DC-LAMP/CD208-, CD86
      , Langerin/CD207-, FXIIIa-, CD1a- cells consistent with the macrophage nature of
      these cells. These fetal DC-SIGN+ cells lack HLA-DR, -DP, -DQ expression.
      Moreover, we show for the first time that they co-express the hyaluronan receptor
      LYVE-1. In contrast, no LYVE-1+ vessel structures, i.e. lymphatic vessels, were
      detected. Human term decidua hosted a variety of CD45+ cells, further phenotyped
      as CD163+, DC-SIGN+, CD68+, HLA-DR+, HLA-A,B,C+. Mature dendritic cells were
      never observed in human term placenta. In summary, human term placenta is an
      immunoprivileged organ without lymphatic drainage and with numerous DC-SIGN+
      macrophages within the chorionic villi. We hypothesize that these cells may
      fulfil a function in innate responses against pathogens as well as be involved in
      the homeostasis of hyaluronan metabolism in the rapidly differentiating placenta.

PMID- 18078990
TI  - Expression of cocaine- and amphetamine-regulated transcript (CART) peptides at
      climbing fibre-Purkinje cell synapses in the rat vestibular cerebellum.
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptides have a wide CNS
      distribution and appear to play an important role in a number of physiological
      processes including reward and reinforcement, feeding, locomotion, stress
      responses and perception of pain. We have further investigated the expression of
      CART peptides in rat cerebellum, using multiple fluorescent antibodies. Dense
      fibre-like immunofluorescence was observed in the molecular layer of the
      vestibular cerebellum (paraflocculus and lobes IX and X of the vermis). There was
      little or no immunofluorescence in any other region of the cerebellum (vermis or
      hemispheres). The immunofluorescence in lobes IX and X of the vermis showed a
      parasagittal banding pattern, with one medial and two lateral bands. We have
      provided several lines of evidence that CART peptides are expressed by climbing
      fibres: (1) There is CART peptide immunofluorescence in the inferior olivary
      complex, the source of climbing fibres. (2) No cerebellar cell bodies were
      labelled by the CART peptide antibody. (3) The developmental profile of CART
      peptide expression was consistent with climbing fibre development and finally (4)
      triple antibody labelling revealed co-expression of CART peptides with VGluT2
      (the glutamate transporter at climbing fibre synapses) at boutons innervating
      calbindin D-28K labelled proximal Purkinje cell dendrites. Analysis of VGluT2 and
      CART peptide labelling in more detail showed that not all climbing fibres in the
      vestibular cerebellum expressed CART peptides but those fibres which did express
      CART peptides were immunofluorescent at all Purkinje cell synapses.

PMID- 18078991
TI  - Disappearance of JAK2 V617F mutation in a rapid leukemic transformed essential
      thrombocythemia patient.

PMID- 18078992
TI  - The two channel catfish intelectin genes exhibit highly differential patterns of
      tissue expression and regulation after infection with Edwardsiella ictaluri.
AB  - Intelectins (IntL) are Ca(2+)-dependent secretory glycoproteins that play a role
      in the innate immune response. The mammalian IntL is also known as lactoferrin
      receptor (LfR) that is involved in iron metabolism. The objective of this study
      was to characterize the intelectin genes in both channel catfish and blue
      catfish, to determine their genomic organization and copy numbers, to determine
      their patterns of tissue expression, and to establish if they are involved in
      defense responses of catfish after bacterial infection. Two types of IntL genes
      have been identified from catfish, and IntL2 was completely sequenced. The
      genomic structure and organization of IntL2 were similar to those of the
      mammalian species and of zebrafish and grass carp, but orthologies cannot be
      established with mammalian IntL genes. The IntL genes are highly conserved
      through evolution. Sequence analysis also indicated the presence of the
      fibrinogen-related domain in the catfish IntL genes, suggesting their structural
      conservations. Phylogenetic analysis suggested the presence of at least two
      prototypes of IntL genes in teleosts, but only one in mammals. The catfish IntL
      genes exhibited drastically different patterns of expression as compared to those
      of the mammalian species, or even with the grass carp gene. The catfish IntL1
      gene is widely expressed in various tissues, whereas the channel catfish IntL2
      gene was mainly expressed in the liver. While the catfish IntL1 is constitutively
      expressed, the catfish IntL2 was drastically induced by intraperitoneal injection
      of Edwardsiella ictaluri and/or iron dextran. Such induction was most dramatic
      when the fish were treated with both the bacteria and iron dextran. While IntL1
      was expressed in all leukocyte cell lines, no expression of IntL2 was detected in
      any of the leukocyte cell lines, suggesting that the up-regulated channel catfish
      IntL2 expression after bacterial infection may be a consequence of the initial
      immune response, and/or a downstream immune response rather than a part of the
      primary immune responses.

PMID- 18078993
TI  - Effectiveness and potential toxicological impact of the PERACLEAN Ocean ballast
      water treatment technology.
AB  - The efficacy and the potential toxicological impact of a proposed ballast water
      treatment (PERACLEAN Ocean) using peracetic acid (PAA) as active substances to
      control species introduction was assessed in both fresh- and salt water
      experiments at very cold water temperatures (1-2 degrees C). Levels of PAA
      gradually declined over the 5-day experiments, while levels of hydrogen peroxide
      remained relatively stable. The rate of decay of both the PAA and hydrogen
      peroxide in water was accelerated in the presence of sediments. Water quality
      properties varied significantly with treatment level with a maximum reduction of
      pH by 2.0 units and a concomitant 20-fold increase in dissolved organic carbon
      levels. Living biomass of organisms in treated water was reduced by 99% after 2
      days. Results from six toxicological tests revealed very steep dose-response
      curves of the treatment. The toxic response of treated waters was higher in fresh
      water than in salt water. The PERACLEAN Ocean treatment may represent an
      effective technology to treat ballast waters under a wide range of temperature
      and salinity conditions. The discharge of treated fresh water may however pose
      some toxicological risk to fresh water receiving environments and to cold waters
      in particular.

PMID- 18078994
TI  - Oxidative stress response in an endangered goodeid fish (Girardinichthys
      viviparus) by exposure to water from its extant localities.
AB  - The oxidative stress response in Girardinichthys viviparus after exposure to
      water from its extant habitants was evaluated. The distribution range of this
      endangered species is currently restricted to a single lake, which receives
      domestic and industrial wastewater treated to a secondary level, but this is also
      contaminated with PCBs. Fish were exposed to water from Lake Texcoco, its extant
      habitat or another one, the Lake Zumpango proposed as a candidate to re
      introduction. To predict the damage induced by sublethal increases in PCBs,
      assessment is also made of fish response to water from these localities enriched
      with PCB mixtures. Adult fish born in the laboratory were exposed to filtered
      surface water or to the PCB-enriched water for 1, 2, 4, 8 and 16 days. An
      assessment of the oxidative stress response in G. viviparus revealed four
      characteristic response patterns that were frequently observed: (1) increased
      lipid-peroxidation (LPOX), depressed SOD and increased CAT; (2) an increase in
      all three biomarkers; (3) reduced LPOX, unchanged SOD and increased CAT; (4)
      increased LPOX and depressed SOD and CAT. Our results demonstrate the complexity
      stress response of this endangered species while indicating that preventive
      measures are urgent to control the discharge of pro-oxidants in its environment.

PMID- 18078995
TI  - Regulation of NFAT by poly(ADP-ribose) polymerase activity in T cells.
AB  - The nuclear factor of activated T cells (NFAT) family of transcription factors is
      pivotal for T lymphocyte functionality. All relevant NFAT activation events upon
      T cells stimulation such as nuclear translocation, DNA binding, and
      transcriptional activity have been shown to be dictated by its phosphorylation
      state. Here, we provide evidence for a novel post-translational modification that
      regulates NFAT. Indeed, NFATc1 and NFATc2 are poly(ADP-ribosyl)ated by poly-ADP
      ribose polymerase-1 (PARP-1). Moreover, we have also found a physical interaction
      between PARP-1 and both NFATc1 and NFATc2. Interestingly, PARP is activated
      during T cell stimulation in the absence of DNA damage, leading to ADP-ribose
      polymers formation and transfer to nuclear acceptor proteins. Our data suggest
      that poly(ADP-ribosyl)ation modulates the activation of NFAT in T cells, as PARP
      inhibition causes an increase in NFAT-dependent transactivation and a delay in
      NFAT nuclear export. Poly(ADP-ribosyl)ation will expedited NFAT export from the
      nucleus directly or by priming/facilitating NFAT phosphorylation. Altogether,
      these data point to PARP-1 and poly(ADP-ribosyl)ation as a novel regulatory
      mechanism of NFAT at nuclear level, suggesting a potential use of PARP as a new
      therapeutic target in the modulation of NFAT.

PMID- 18078996
TI  - Anti-lipopolysaccharide factor in Litopenaeus vannamei (LvALF): a broad spectrum
      antimicrobial peptide essential for shrimp immunity against bacterial and fungal
      infection.
AB  - Antimicrobial peptides are an essential component of the innate immune system of
      most organisms. Expressed sequence tag analysis from various shrimp (Litopenaeus
      vannamei) tissues revealed transcripts corresponding to two distinct sequences
      (LvALF1 and LvALF2) with strong sequence similarity to anti-lipopolysaccharide
      factor (ALF), an antimicrobial peptide originally isolated from the horseshoe
      crab Limulus polyphemus. Full-length clones contained a 528bp transcript with a
      predicted open reading frame coding for 120 amino acids in LvALF1, and a 623bp
      transcript with a predicted open reading frame coding for 93 amino acids in
      LvALF2. A reverse genetic approach was implemented to study the in vivo role of
      LvALF1 in protecting shrimp from bacterial, fungal and viral infections.
      Injection of double-stranded RNA (dsRNA) corresponding to the LvALF1 message
      resulted in a significant reduction of LvALF1 mRNA transcript abundance as
      determined by qPCR. Following knockdown, shrimp were challenged with low
      pathogenic doses of Vibrio penaeicida, Fusarium oxysporum or white spot syndrome
      virus (WSSV) and the resulting mortality curves were compared with controls. A
      significant increase of mortality in the LvALF1 knockdown shrimp was observed in
      the V. penaeicida and F. oxysporum infections when compared to controls, showing
      that this gene has a role in protecting shrimp from both bacterial and fungal
      infections. In contrast, LvALF1 dsRNA activated the sequence-independent innate
      anti-viral immune response giving increased protection from WSSV infection.

PMID- 18078997
TI  - Structural characterization of a mutated, ADCC-enhanced human Fc fragment.
AB  - We report here the three-dimensional structure of a human Fc fragment engineered
      for enhanced antibody dependent cell mediated cytotoxicity (ADCC). The triple
      mutation S239D/A330L/I332E ('3M') was introduced into the C(H)2 portion of a
      human immunoglobulin G1 (IgG1) Fc. These three substitutions typically result in
      an about 10-100-fold increase in human IgG1 binding to human Fc gamma RIIIA
      (CD16). The recombinantly produced Fc/3M fragment was crystallized and its
      structure solved at a resolution of 2.5A using molecular replacement. No dramatic
      structural changes were observed in Fc/3M when compared with unmutated human Fc
      fragments. However, we found that the relative positions of its C(H)2 domains
      allowed for an unusually 'open' conformation of the entire fragment. Although
      this particular structural feature could be due to crystallization artifacts or
      intrinsic variability, we propose that molecular mechanisms at the basis of the
      enhanced interaction between Fc/3M and CD16 could include enhanced Fc openness as
      well as the introduction of additional hydrophobic contacts, hydrogen bonds
      and/or electrostatic interactions at the corresponding interface. The existence
      of a more pronounced cleft between the two Fc chains as well as of repulsive,
      electrostatic intra-chain interactions may also account in part for the decreased
      thermostability of both Fc/3M and a 3M-modified humanized anti-human EphA2 IgG1
      when compared with their respective unmutated counterparts.

PMID- 18078998
TI  - Autism: maternally derived antibodies specific for fetal brain proteins.
AB  - Autism is a profound disorder of neurodevelopment with poorly understood
      biological origins. A potential role for maternal autoantibodies in the etiology
      of some cases of autism has been proposed in previous studies. To investigate
      this hypothesis, maternal plasma antibodies against human fetal and adult brain
      proteins were analyzed by western blot in 61 mothers of children with autistic
      disorder and 102 controls matched for maternal age and birth year (62 mothers of
      typically developing children (TD) and 40 mothers of children with non-ASD
      developmental delays (DD)). We observed reactivity to two protein bands at
      approximately 73 and 37kDa in plasma from 7 of 61 (11.5%) mothers of children
      with autism (AU) against fetal but not adult brain, which was not noted in either
      control group (TD; 0/62 p=0.0061 and DD; 0/40 p=0.0401). Further, the presence of
      reactivity to these two bands was associated with parent report of behavioral
      regression in AU children when compared to the TD (p=0.0019) and DD (0.0089)
      groups. Individual reactivity to the 37kDa band was observed significantly more
      often in the AU population compared with TD (p=0.0086) and DD (p=0.002) mothers,
      yielding a 5.69-fold odds ratio (95% confidence interval 2.09-15.51) associated
      with this band. The presence of these antibodies in the plasma of some mothers of
      children with autism, as well as the differential findings between mothers of
      children with early onset and regressive autism may suggest an association
      between the transfer of IgG autoantibodies during early neurodevelopment and the
      risk of developing of autism in some children.

PMID- 18078999
TI  - Uptake of influenza vaccination among children with diabetes--a re-audit.

PMID- 18079000
TI  - In vivo imaging of murine retinal ganglion cells.
AB  - Current methods for in vivo retinal ganglion cells (RGCs) imaging involve either
      retrograde or intravitreal injection of chemical or biological tracers, which are
      invasive and may require repeated injection for serial long-term assessment. We
      have developed a confocal scanning laser ophthalmoscope technique (blue-light
      CSLO or bCSLO) to image retinal ganglion cells (RGCs) in mice expressing cyan
      fluorescent protein under the control of a Thy-1 promoter. Fluorescent spots
      corresponding to CFP-expressing retinal ganglion cells were discernable with the
      bCSLO. 96.1+/-2.6% of CFP expressing cells also were retrograde labeled with DiI
      indicating the bCSLO imaged fluorescent spots are RGCs. The imaging of Thy-1
      promoter-driven CFP expression in these mice could serve as a sensitive indicator
      to reflect the integrity of RGCs, and provides a non-invasive method for
      longitudinal study of the mechanism of RGC degeneration and the effect of
      neuroprotective agents.

PMID- 18079001
TI  - Oxidative stress during acute FIV infection in cats.
AB  - Oxidative stress is thought to contribute to the pathogenesis of HIV infection in
      humans. For example, CD4(+) T cells are particularly affected in HIV patients and
      oxidative stress may also contribute to impairment of neutrophil function in
      HIV/AIDS patients. Since cats infected with FIV develop many of the same
      immunological abnormalites as HIV-infected humans, we investigated effects of
      acute FIV infection on oxidative stress in cats. Cats were infected with a
      pathogenic strain of FIV and viral load, changes in neutrophil number, total
      blood glutathione, malondiadehye, antioxidant enzyme concentrations, and reduced
      glutathione (GSH) concentration in leukocytes were measured sequentially during
      the first 16 weeks of infection. We found that superoxide dismutase and
      glutathione peroxidase concentrations in whole blood increased significantly
      during acute FIV infection. In addition, neutrophil numbers increased
      significantly during this time period, though their intracellular GSH
      concentrations did not change. In contrast, the numbers of CD4(+) T cells
      decreased significantly and their intracellular GSH concentration increased
      significantly, while intracellular GSH concentrations were unchanged in CD8(+) T
      cells. However, by 16 weeks of infection, many of the abnormalities in oxidative
      balance had stabilized or returned to pre-inoculation values. These results
      suggest that acute infection with FIV causes oxidative stress in cats and that
      CD4(+) T cells appear to be preferentially affected. Further studies are required
      to determine whether early treatment with anti-oxidants may help ameliorate the
      decline in CD4(+) T cell number and function associated with acute FIV infection
      in cats.

PMID- 18079002
TI  - Antigenic profiles of recombinant proteins from Mycobacterium avium subsp.
      paratuberculosis in sheep with Johne's disease.
AB  - Methods to improve the ELISA test to detect Mycobacterium avium subsp.
      paratuberculosis have been explored over several years. Previously, selected
      recombinant proteins of M. avium subspecies paratuberculosis were found to be
      immunogenic in cattle with Johne's disease. In the present study, antibody
      responses of infected and healthy sheep were evaluated using 18 purified
      recombinant proteins in an ELISA-based format for the serodiagnosis of ovine
      paratuberculosis. These selected recombinant proteins represent heat shock
      proteins, hypothetical proteins and cell surface proteins of M. avium subsp.
      paratuberculosis. Whereas, Map0862 (a gene uniquely present in M. avium
      subspecies paratuberculosis) and Map3786 encoded protein solicited the strongest
      antibody response in infected sheep. The protein encoded by Map2116c showed the
      weakest antibody response among the animals tested. Although none of the
      recombinant proteins detected all 11 infected sheep singly, antibodies to Map0862
      were detected in 9 of 11 (81%) infected sheep. Furthermore, ovine responses to
      these selected antigens were assessed temporally over the course of 1 year during
      which we found a spiking effect rather than an incremental increase of antibody
      reactivity. This study evaluated multiple M. avium subsp. paratuberculosis
      recombinant proteins in an ELISA-based format for sheep.

PMID- 18079003
TI  - Activity of different vaccine-associated promoter elements in human dendritic
      cells.
AB  - Vaccine design approaches that target dendritic cells (DC) aim at achieving high
      levels of transgene expression. Careful selection of the promoter element driving
      the foreign gene is therefore important. We have constructed adenovirus vectors
      carrying the gene for enhanced green fluorescent protein (eGFP) driven by three
      different promoters, CMV, CMV5 and ubiquitin C (UbC) promoter, and analysed their
      activity in different populations of human DC, namely blood plasmacytoid (pDC)
      and myeloid DC (mDC), monocyte-derived DC (moDC), Langerhans (LC) and dermal type
      DC (dDC). Although the CMV5 promoter was more active than the other two promoters
      in the HeLa and 911HER cell lines, in human DC the highest level of transgene
      expression was seen with the CMV promoter. There was very low-level eGFP
      expression in all cell types transduced with the UbC promoter. Highest eGFP
      expression levels were observed in moDC, cultured mDC and LC and the lowest
      levels in pDC. Expression of eGFP was augmented in all DC populations upon
      stimulation with CD40 ligand (CD40L). These findings demonstrate that the CMV
      promoter is the most effective of the three promoters tested in a range of
      different human DC populations.

PMID- 18079004
TI  - Failed efficacy of soluble human CD83-Ig in allogeneic mixed lymphocyte reactions
      and experimental autoimmune encephalomyelitis: implications for a lack of
      therapeutic potential.
AB  - Soluble forms of CD83, a dendritic cell-specific surface glycoprotein, have been
      strongly proposed to be of therapeutic utility in inflammatory conditions such as
      multiple sclerosis and transplantation. We demonstrate here, however, that
      eukaryotically expressed, recombinant soluble human CD83-Ig molecules fail to
      achieve efficacy in model systems for those conditions: mouse experimental
      autoimmune encephalomyelitis models in vivo or in mixed lymphocyte reactions in
      vitro. These results raise concern as to the viability of a eukaryotically
      expressed soluble CD83 strategy for clinical therapeutic use.

PMID- 18079005
TI  - Effects of intramuscular and peritonsillar injection of tramadol before
      tonsillectomy: a double blind, randomized, placebo-controlled clinical trial.
AB  - BACKGROUND/AIMS: Our objective was to investigate the efficacy of intramuscular
      injection and peritonsillar infiltration of tramadol to prevent pain in children
      undergoing tonsillectomy. METHODS: In a double-blinded trial, 45 children were
      randomized into three groups: infiltration anesthesia with tramadol (2 mgkg(-1))
      to the peritonsillar area (INF group, n=15), intramuscular analgesia with
      tramadol (2 mgkg(-1)) (IM group, n=15), and the placebo controls (PL group,
      n=15). Visual analog scale (VAS) scores for pain assessment, heart rate (HR) and
      mean arterial pressure (MAP) during and after anesthesia were recorded. RESULTS:
      Mean HR values were higher in INF than PL group at 10th, 20th, and 30th minutes
      of operation (P<0.05). Nine children required analgesics within the first hour
      after surgery in PL compared to 1 child in INF group (P=0.036). VAS scores on
      awakening were significantly better in INF than PL group (P=0.015). The
      difference between IM and PL groups was not significant for any of the
      parameters. CONCLUSION: Peritonsillar infiltration with tramadol provided good
      intraoperative analgesia, less postoperative pain on awakening and lower
      analgesic requirement within the first hour after surgery.

PMID- 18079006
TI  - Investigating the sensitivity of a fluorescence-based microarray for the
      detection of fruit-tree viruses.
AB  - An oligonucleotide microarray for the detection of some fruit-tree viruses was
      designed and its theoretical detection limit was assessed using Cy3-labelled
      oligonucleotides. The real sensitivity of the microarray was compared for
      different kinds of fluorescently labelled targets: (a) cDNA and PCR amplified
      targets, (b) PCR amplified targets labelled using three different labelling
      methods. In the first case (a), the number of viral cDNA molecules was below the
      assessed detection limit of the microarray and only PCR amplified targets were
      detected. A second comparison (b), done on 3 selected viruses, included indirect
      labelling, the direct incorporation of labelled-dUTPs, and the use of Cy3
      labelled primer. The targets labelled most intensively were produced by the Cy3
      primer labelling (2 of 3 viruses) or by the indirect labelling method (1 of 3
      viruses), the weakest signal showed targets labelled directly (all 3 viruses).
      The use of Cy3-primer labelling involved the simplest preparation and the lowest
      cost, however occasional weak cross-hybridization appeared. The indirect
      labelling method was of the highest specificity. The probes hybridizing near the
      3-end of the targets showed the lowest intensities of fluorescent signal.

PMID- 18079007
TI  - A highly sensitive and versatile virus titration assay in the 96-well microplate
      format.
AB  - This report describes a fast, reproducible, inexpensive and convenient assay
      system for virus titration in the 96-well format. The micromethod substantially
      increases assay throughput and improves the data reproducibility. A highly
      simplified variant of virus quantification is based on immunohistochemical
      detection of virus amplification foci obtained without use of agarose or
      semisolid overlays. It can be incorporated into several types of routine
      virological assays successfully replacing the laborious and time-consuming
      conventional methods based on plaque formation under semisolid overlays. The
      method does not depend on the development of CPE and can be accommodated to assay
      viruses with substantial differences in growth properties. The use of enhanced
      immunohistochemical detection enabled a five- to six-fold reduction of the total
      assay time. The micromethod was specifically developed to take advantage of
      multichannel pipettor use to simplify handling of a large number of samples. The
      method performs well with an inexpensive low-power binocular, thus offering a
      routine assay system usable outside of specialized laboratory setting, such as
      for testing of clinical or field samples. When used in focus reduction
      neutralization tests (FRNT), the method accommodates very small volumes of immune
      serum, which is often a decisive factor in experiments involving small rodent
      models.

PMID- 18079008
TI  - Detection of the mycovirus OMSV in the edible mushroom, Pleurotus ostreatus,
      using an SPR biosensor chip.
AB  - A surface plasmon resonance (SPR) biosensor chip was developed for the rapid
      detection of the oyster mushroom spherical virus (OMSV), which causes a mushroom
      die-back disease, the symptoms of which include malformed fruiting bodies and
      retarded mycelial growth in the cultivated edible mushroom, Pleurotus ostreatus.
      An anti-OMSV monoclonal antibody (mAb) was generated initially using purified
      OMSV viral particles. For the fabrication of the biosensor chip, the anti-OMSV
      mAb was layered onto an activated carboxymethyl-dextran (CM-Dex) gold thin film.
      Analysis on the SPR angle shift showed that the bound mAb was 6.7 ng/mm2 of the
      chip surface. Subsequently, the biosensor chip was applied to the detection of
      OMSV in the mushroom mycelial extract. It detected specifically OMSV in the
      extract in a concentration-dependent manner. Finally, the biosensor chip was
      employed for the detection of OMSV in the mushroom fruiting bodies collected from
      10 commercial farms. Among the tested samples, OMSV was found to infect fruiting
      bodies from a farmland, and this was confirmed further via immunoblot analysis
      and a TAS-ELISA assay. In conclusion, the SPR biosensor chip combined with an
      anti-OMSV mAb evidenced superior performance, particularly with regard to the
      prompt detection of OMSV infection.

PMID- 18079009
TI  - Development of a suspension serum-free helper-dependent adenovirus production
      system and assessment of co-infection conditions.
AB  - Helper-dependent adenovirus (HDAd), deleted in all viral protein-coding sequences
      has been designed to reduce immune response and favor long-term expression of
      therapeutic genes in clinical programs. Its production requires co-infection of
      E1-complementing cells with helper adenovirus (HAd). Significant progresses have
      been made in the molecular design of HDAd, but large scale production remains a
      challenge. In this work, a scalable system for HDAd production is designed and
      evaluated focusing on the co-infection step. A human embryo kidney 293 (293)
      derived cell line, the 293SF/FLPe was generated to produce efficiently HDAd while
      restricting the packaging of HAd. This cell line was adapted to grow in
      suspension and in serum-free medium. Multiplicity of infection (MOI) of HDAd
      ranging from 0.1 to 50 was evaluated in presence of HAd at a MOI of 5. Optimal
      MOIs for HDAd amplification were found in the range of 5-10. HAd contamination
      was only 1%. These results were validated in a 3 L bioreactor under controlled
      operating conditions where a higher HDAd yield of 2.6 x 10(9) viral particles
      (VP)/mL or 3.5 x 10(8) infectious units (IU)/mL of HDAd was obtained.

PMID- 18079010
TI  - Fearfulness in a large N/Nih genetically heterogeneous rat stock: differential
      profiles of timidity and defensive flight in males and females.
AB  - Anxiety-related behaviors were evaluated across various tests in a large sample
      (n=787, both sexes) of genetically heterogeneous (N/Nih-HS) rats, derived from an
      eight-way cross of inbred strains. These tests either evoke unlearned (black
      white box, BWB-; novel-cage activity, NACT-; elevated "zero" maze, ZM-; baseline
      acoustic startle response, BAS-) or learned (fear-potentiated startle, FPS-; two
      way active-shuttle box-avoidance acquisition, SHAV-) anxious/fearful responses.
      The results showed that, with the exception of fear-potentiated startle, almost
      all (unlearned and learned) behaviors assessed fit with a pattern of sex effects
      characterized by male rats as being more fearful than females. We applied factor
      analyses (oblique rotation) to each sex, with the final two-factor solution
      showing: (1) a first factor (labelled as "Timidity") comprising BWB, NACT and ZM
      variables in both sexes, plus SHAV responding in the case of males, and (2) a
      second factor (called "Defensive Flight") which grouped BAS, FPS, and SHAV
      responding in both sexes. An additional regression analysis showed significant
      influences of (unlearned) risk assessment (i.e. stretch-attendance) behavior on
      SHAV in males, while FPS was the main variable positively influencing SHAV (in
      the intermediate and advanced phases of acquisition) in females. This indicates,
      for the first time, that fear-potentiated startle may have a facilitating role in
      the rat's active responses (at least in females) to the cue in the intermediate
      to advanced phases (i.e. when the initial "passive avoidance/active avoidance"
      begins to fade) of shuttle box avoidance acquisition. The results of this first
      extensive behavioral evaluation of N/Nih-HS rats are discussed in terms of their
      potential usefulness for present and future neurobehavioral and genetic studies
      of fearfulness/anxiety.

PMID- 18079011
TI  - Recombinant ligA for leptospirosis diagnosis and ligA among the Leptospira spp.
      clinical isolates.
AB  - Rapid diagnosis for differentiation of leptospirosis from other pyrogenic
      infections prevailing in the same locality is imperative for proper treatment.
      During infection, the pathogenic Leptospira spp. express virulence factors which
      induce antibody responses in the infected host. In this study, 50 referenced
      Leptospira spp. belonging to six genomospecies and 10 L. interrogans clinical
      isolates were studied for the presence of a gene encoding an in vivo expressed,
      surface exposed, immunoglobulin-like protein, LigA, by using PCR and southern
      hybridization specific to the 5' terminus sequence of the DNA. LigA was also
      detected in the Leptospira spp. whole cell homogenates by a direct ELISA using a
      mouse antiserum to the C-terminal portion of recombinant LigA (cLigA) as a
      detection reagent. All pathogenic Leptospira spp. except one of the two strains
      of L. santorasai were positive for the gene and its phenotype while all of the L.
      borgpetersenii and L. biflexa strains were negative. Recombinant cLigA was used
      as an antigen in ELISAs for detecting IgM and IgG in the sera of leptospirosis
      patients and in the sera of patients with other febrile illnesses and healthy
      subjects. When acute phase sera were tested by the cLigA IgM- and IgG-ELISAs, 92%
      and 100% of the MAT-positive sera were positive, respectively. The diagnostic
      sensitivity was 100% when both IgM- and IgG-ELISAs were performed on the same
      acute phase sera and the results were combined. Acute and convalescence sera of
      patients who were Leptospira culture positive but MAT/IgM-dipstick negative gave
      88% and 100% positives by combined cLigA IgM/IgG ELISAs. The diagnostic
      specificities for the cLigA IgM- and IgG-ELISAs were 98% and 100%, respectively.
      Our cLigA based-serology has a high potential for early diagnosis of
      leptospirosis especially when the culture and MAT results are not yet available.

PMID- 18079012
TI  - Molecular characterisation and phylogenetic analysis of Chronic bee paralysis
      virus, a honey bee virus.
AB  - The complete sequences of the two major RNAs of Chronic bee paralysis virus
      (CBPV) have been determined. RNA 1 (3674nt long) and RNA 2 (2305nt long) are
      positive single-stranded RNAs that are capped but not polyadenylated. The 3' ends
      of both RNAs are unreactive to polymerisation or ligation even in denaturing
      conditions, a feature already observed in alphanodavirus RNAs. The three
      previously described smaller RNAs [Overton, H.A., Buck, K.W., Bailey, L., et al.,
      1982. Relationships between the RNA components of Chronic bee-paralysis virus and
      those of chronic bee-paralysis virus associate. J. Gen. Virol. 63, 171-179], were
      not detected in this study, supporting the hypothesis that they would correspond
      to the three RNAs of the Chronic bee paralysis satellite virus (CBPSV). RNA 1 and
      RNA 2 encoded three and four overlapping open reading frames (ORFs),
      respectively. The amino acid sequences deduced from the ORF 3 on RNA 1 shared the
      conserved motifs of the RNA-dependent RNA polymerase (RdRp) sequence and
      presented similarities with members of the Nodaviridae and Tombusviridae
      families. However, no similarities were found between the other CBPV deduced
      amino acid sequences and sequences in the NCBI databases, suggesting that CBPV is
      the prototype of a new family of positive single-stranded RNA viruses.

PMID- 18079013
TI  - Preparation and in vitro evaluation of the antiviral activity of the Acyclovir
      complex of a beta-cyclodextrin/poly(amidoamine) copolymer.
AB  - A poly(amidoamine) (PAA) copolymer with beta-cyclodextrin was obtained by
      polyaddition reaction of 6-deoxy-6-amino-beta-cyclodextrin (beta-CD-NH(2)) and 2
      methylpiperazine to 2,2-bis(acrylamido)acetic acid in aqueous medium. This beta
      CD/PAA copolymer bears beta-CD units along the macromolecular chain, is water
      soluble and non-cytotoxic. The complexing capacity of beta-CD/PAA was determined
      using an antiviral drug, Acyclovir, as a model of poorly water-soluble drug.
      Complex formation was confirmed by means of DSC and FTIR analyses. beta-CD/PAA
      can solubilize up to 11% w/w of Acyclovir notably increasing the aqueous
      solubility of the drug. The in vitro release studies showed the dependence of
      Acyclovir release rate on the solution pH. The antiviral activity of Acyclovir
      beta-CD/PAA complex was evaluated against herpes simplex virus type I in cell
      cultures. The Acyclovir beta-CD/PAA complex exhibited a higher antiviral activity
      than the free drug.

PMID- 18079014
TI  - Social capital, political trust and purchase of illegal liquor: a population
      based study in southern Sweden.
AB  - AIMS: To investigate the association between political trust in the Riksdag (the
      national parliament in Sweden) and having purchased illegal liquor during the
      past 12 months. METHODS: The 2004 public health survey in Skane is a cross
      sectional postal questionnaire study answered by 27,757 respondents aged 18-80
      with a 59% response rate. A logistic regression model was used to investigate the
      associations between political trust and having purchased illegal liquor during
      the past 12 months. Multivariate analyses of political trust and having purchased
      illegal liquor were performed in order to investigate the importance of possible
      confounders (including generalized/horizontal trust in other people). RESULTS: A
      21.2% fraction of the men and 9.6% of the women had purchased illegal alcohol
      during the past 12 months. A total of 17.3% and 11.6% of the male and female
      respondents, respectively, reported that they had no trust at all in the national
      parliament, and another 38.2% and 36.2%, respectively, reported that their
      political trust was not particularly high. Respondents in younger age groups,
      with medium/low education, economic stress, low horizontal trust and not
      particularly high and no political trust at all and no opinion had significantly
      higher levels of having purchased illegal liquor. The significant odds ratios of
      having purchased illegal liquor in the not particularly high political trust and
      no political trust at all categories were somewhat reduced although still
      significant after multiple adjustments. CONCLUSION: The results suggest that
      political trust may have an independent effect on the propensity to purchase
      illegal liquor in Sweden.

PMID- 18079015
TI  - Potentially functional polymorphisms of EXO1 and risk of lung cancer in a Chinese
      population: A case-control analysis.
AB  - Exonuclease 1 (EXO1) is an important nucleases involved in mismatch repair system
      that contributes to maintain genomic stability, to modulate DNA recombination,
      and to mediate cell cycle arrest. Potentially functional polymorphisms in EXO1
      may alter cancer risks by influencing the repair activity of EXO1. Therefore, we
      hypothesized that single nucleotide polymorphisms (SNPs) in EXO1 were associated
      with risk of lung cancer. To test this hypothesis, we genotyped five common SNPs
      (rs1776177A/G, rs1047840G/A (Glu589Lys), rs1776148G/A (Gly670Glu), rs9350C/T
      (Leu757Pro) and rs851797T/C) that tag eight SNPs located at exon regions of EXO1
      by using the Illumina high-throughput genotyping platform in 500 incident lung
      cancer cases and 517 cancer-free controls in a Chinese population. Significant
      differences of allele and genotype distributions were observed in Glu589Lys
      (rs1047840) of EXO1 between the cases and controls (P=0.028 and 0.025 for allele
      and genotype distributions, respectively). Logistic regression analyses revealed
      that individuals carrying the variant 589Lys allele (589Glu/Lys or 589Lys/Lys)
      had a significantly increased risk of lung cancer [adjusted odds ratio (OR)=1.41,
      95% confidential interval (CI)=1.09-1.84] compared with those who carried the
      wild-type homozygote (589Glu/Glu). Furthermore, we found that haplotype AAGTT was
      more frequent in cases than in controls (P<0.001 for both two-sided chi(2)-test
      and 1000 times permutation tests). These results suggest that the EXO1 Glu589Lys
      polymorphism and its surrounding regions might be genetic susceptibility markers
      for lung cancer in this study population.

PMID- 18079016
TI  - Prolonged control of bone metastases in non-small-cell lung cancer patients
      treated with gefitinib.
AB  - We describe two non-small-cell lung cancer (NSCLC) patients in which treatment
      with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs)
      gefitinib produced a prolonged control of bone disease. In the first patient, a
      48-year-old male with adenocarcinoma (ADC) of the lung and multiple bone
      metastases, the bone scan became completely negative following treatment with
      gefitinib for 9 months. The patient remained alive and with no evidence of bone
      metastases for 20 months, despite two local recurrences that were surgically
      removed. Similarly, the bone scan of the second patient, a 49-year-old male with
      ADC of the lung and bone metastases, became negative after 6 months on gefitinib.
      The molecular mechanisms potentially involved in this phenomenon are discussed.

PMID- 18079017
TI  - Evolutionary potential of hidden genetic variation.
AB  - The ability of a population to respond to natural or artificial selection
      pressures is determined by the genetic architecture of the selected trait. It is
      now widely acknowledged that a substantial part of genetic variability can be
      buffered or released as the result of complex genetic interactions. However, the
      impact of hidden genetic diversity on phenotypic evolution is still not clear.
      Here, we argue that a common term to describe the impact of hidden genetic
      variation on phenotypic change is needed and will help to provide new insights
      into the contribution of different components of genetic architectures to the
      evolvability of a character. We introduce the 'genetic charge' concept, to
      describe how the architecture of a trait can be 'charged' with potential for
      evolutionary change that can later be 'discharged' in response to selection.

PMID- 18079018
TI  - Long-term evolution of a nosocomial outbreak of Pseudomonas aeruginosa producing
      VIM-2 metallo-enzyme.
AB  - From April 1996 to July 2004, an outbreak of metallo-beta-lactamase-positive
      (MBL) Pseudomonas aeruginosa occurred in the haematology ward at Nantes
      University Hospital in France. Fifty-nine patients were carriers of VIM-2
      positive strains of whom 14 were infected (mostly urinary tract infections and
      pneumonia). Pulsed-field gel electrophoresis identified related isolates
      demonstrating resistance to all beta-lactams, aminoglycosides, fluoroquinolones,
      fosfomycin, rifampicin but not colistin. The bla(VIM-2) gene responsible for VIM
      2 MBL was not plasmid-encoded but part of a novel type of class 1 integron. VIM-2
      positive strains were mostly from urine samples and clinical data suggest that in
      the absence of therapeutic guidelines, piperacillin-tazobactam or aztreonam may
      be a reliable choice for treating infections with MBL-producing strains.

PMID- 18079019
TI  - Multi-resistant infections in repatriated patients after natural disasters:
      lessons learned from the 2004 tsunami for hospital infection control.
AB  - Infections are a frequent consequence of natural disasters. Repatriated victims
      may require hospital care due to multiple fractures, pneumonia or wound
      infections caused by multi-resistant pathogens that require specific infection
      control measures. To address potential pitfalls of infection control and clinical
      care in repatriated patients, we sought to provide microbiological insight into
      the possible origins of multi-drug antibiotic resistance in survivors of natural
      disasters. A review of the medical literature was performed from 1986 to 2006
      with an emphasis on the 2004 tsunami disaster in the Indian Ocean. After natural
      disasters, polymicrobial infections may occur following heavy inoculation during
      trauma. Multi-resistant Gram-negative pathogens are more prevalent than Gram
      positive bacteria. A high incidence of extended spectrum beta-lactamase-producing
      bacteria and difficult-to-treat fungal infections in otherwise immunocompetent
      hosts may challenge routine hospital care. We recommend that survivors of natural
      disasters should be kept in pre-emptive contact isolation during air transport
      and hospitalisation until the results of all microbiological cultures become
      available. A meticulous diagnostic work-up is necessary upon admission and
      empiric antibiotic treatment should be avoided. Infections may also become
      manifest after several weeks of hospitalisation. In case of life-threatening
      infection, antibiotic therapy should cover non-fermenting pathogens.

PMID- 18079020
TI  - Clostridium difficile, ethnicity and religion.

PMID- 18079021
TI  - Virulence determinants in vancomycin-resistant Enterococcus faecium vanB: clonal
      distribution, prevalence and significance of esp and hyl in Australian patients
      with haematological disorders.
AB  - European studies have suggested that the esp gene and other virulence factors
      have roles in vancomycin-resistant Enterococcus faecium (VREfm) infections. The
      aim of this study was to examine the relationship between the spectrum of
      clinical disease and putative virulence factors in vanB VREfm isolates. A
      multiplex polymerase chain reaction was used to amplify potential virulence genes
      (asa1, gel E, cylA, esp and hyl) in VREfm isolates obtained from an Australian
      population of haematology patients. Clonality was assessed by pulsed-field gel
      electrophoresis (PFGE) and automated ribotyping. Infection, requirement for
      intensive care unit (ICU) admission and all-cause 30-day mortality were used as
      clinical indicators of organism virulence. Forty-one VREfm vanB isolates (41
      patients; 14 infected and 27 colonised only) were analysed. Thirty-five of these
      isolates were typed by PFGE, 31 of which were represented by three clusters. The
      esp gene was identified in 22 of 27 (81.5%) screening and 11 of 14 (78.6%)
      infection-associated isolates. One isolate was hyl gene positive, and no isolate
      contained asa1, gel E or cylA genes. VREfm infection was independently associated
      with host factors (underlying diagnosis of acute myeloid leukaemia, age <or=60
      years) but not with presence of the esp gene. ICU admission was negatively
      associated with presence of the esp gene (OR: 0.05; 95% CI: 0.01-0.61; P=0.02).
      There was no association between 30-day mortality and host factors or the
      presence of the esp gene. When compared to European and US reports, a high esp
      gene prevalence and low hyl gene prevalence was observed in polyclonal VRE
      isolates obtained from this immunocompromised population.

PMID- 18079023
TI  - Implications of age and diet on canine cerebral cortex transcription.
AB  - Mechanisms contributing to age-related cognitive decline are poorly defined.
      Thus, we used canine microarrays to compare gene expression profiles of brain
      tissue from geriatric and young adult dogs. Cerebral cortex samples were
      collected from six geriatric (12-year old) and six young adult (1-year old)
      female beagles after being fed one of two diets (animal protein-based versus
      plant-protein based) for 12 months. RNA samples were hybridized to Affymetrix
      GeneChip Canine Genome Arrays. Statistical analyses indicated that the age had
      the greatest impact on gene expression, with 963 transcripts differentially
      expressed in geriatric dogs. Although not as robust as age, diet affected mRNA
      abundance of 140 transcripts. As demonstrated in aged rodents and humans,
      geriatric dogs had increased expression of genes associated with inflammation,
      stress response, and calcium homeostasis and decreased expression of genes
      associated with neuropeptide signaling and synaptic transmission. In addition to
      its existing strengths, availability of gene sequence information and commercial
      microarrays make the canine a powerful model for studying the effects of aging on
      cognitive function.

PMID- 18079022
TI  - Amyloid-beta peptide binds to microtubule-associated protein 1B (MAP1B).
AB  - Extracellular and intraneuronal formation of amyloid-beta aggregates have been
      demonstrated to be involved in the pathogenesis of Alzheimer's disease. However,
      the precise mechanism of amyloid-beta neurotoxicity is not completely understood.
      Previous studies suggest that binding of amyloid-beta to a number of targets have
      deleterious effects on cellular functions. In the present study we have shown for
      the first time that amyloid-beta 1-42 bound to a peptide comprising the
      microtubule binding domain of the heavy chain of microtubule-associated protein
      1B by the screening of a human brain cDNA library expressed on M13 phage. This
      interaction may explain, in part, the loss of neuronal cytoskeletal integrity,
      impairment of microtubule-dependent transport and synaptic dysfunction observed
      previously in Alzheimer's disease.

PMID- 18079024
TI  - Levodopa ameliorates learning and memory deficits in a murine model of
      Alzheimer's disease.
AB  - Dopamine plays an important role in learning and memory processes. A deficit of
      this neurotransmitter as it is apparent in Alzheimer's disease (AD) may
      contribute to cognitive decline, a major symptom of AD patients. The aim of this
      study was to elucidate whether or not stimulation of the dopaminergic system
      leads to an improvement of cognitive function and reduction of non-cognitive
      behavioral alterations in a murine model of AD. Transgenic and wild type male
      mice of the TgCRND8 line were treated either with the dopamine precursor levodopa
      or vehicle and tested in two learning tasks, the object-recognition task and the
      Barnes maze test. Additionally 24 h spontaneous behavior in the home cage was
      analyzed. In both memory tasks wild type mice performed significantly better than
      transgenics. However, transgenics treated with levodopa showed a significant
      object recognition memory and improved acquisition of spatial memory in the
      Barnes maze compared to vehicle treated transgenics. Concerning spontaneous
      behavior transgenic mice performed much more stereotypies than wild types.
      However, there was a trend for reduced stereotypies in the levodopa group in the
      time the drug was active. Neurochemical analysis revealed elevated levels of
      dopamine in the neostriata and frontal cortices and reduced levels in the
      hippocampi of transgenic mice compared to wild types. Thus cognitive deficits and
      stereotypies may be due to changes in the dopaminergic system as they could be
      ameliorated by levodopa treatment, that might also have a therapeutic
      significance for AD.

PMID- 18079025
TI  - Number of children is associated with neuropathology of Alzheimer's disease in
      women.
AB  - OBJECTIVE: To examine the association between number of born children and
      neuropathology of Alzheimer's disease (AD). METHODS: The brains of 86 subjects
      with data on the number of biological children born, were studied postmortem.
      Primary analyses included 73 subjects (average age at death=80; 42 women) devoid
      of cerebrovascular disease associated lesions (i.e., infarcts) or of non-AD
      related neuropathology. Women were significantly older at death than men (85.6
      vs. 73.4; p<.0005) but did not differ significantly from men in number of
      children or dementia severity. Secondary analyses included 13 additional subjects
      who had concomitant cerebrovascular disease. Density of neuritic plaques (NPs)
      and neurofibrillary tangles (NFTs) in the hippocampus, entorhinal cortex,
      amygdala and multiple regions of the cerebral cortex, as well as composites of
      these indices reflecting overall neuropathology, were analyzed. For men and women
      separately, partial correlations, controlling for age at death and dementia
      severity, were used to assess the associations of number of children with these
      neuropathological variables. RESULTS: Among women, all the partial correlations
      were positive, with statistical significance for overall neuropathology (r=.37;
      p=.02), overall NPs (r=.36; p=.02), and for NPs in the amygdala (r=.47; p=.002).
      Among men, none of the partial correlations were statistically significant.
      Results of the secondary analyses were similar. CONCLUSIONS: Since the
      associations between number of children and neuropathology of AD were found for
      women only, they might reflect sex-specific mechanisms (such as variations in
      estrogen or luteinizing hormone levels) rather than social, economic, biological
      or other mechanisms common to both men and women.

PMID- 18079027
TI  - Stabilizing the glycosylation pattern of influenza B hemagglutinin following
      adaptation to growth in eggs.
AB  - The currently circulating influenza B viruses from both antigenic lineages
      contain an N-linked glycosylation site in the hemagglutinin (HA) protein at
      positions of 196 or 197. However, egg adaptation caused the loss of the
      glycosylation site that could impact virus antigenicity and vaccine efficacy. The
      effect of the 196/197 glycosylation site on influenza B virus growth and
      antigenicity was systemically evaluated in this study by the molecular approach.
      Paired recombinant 6:2 reassortant influenza B vaccine strains, with or without
      the 196/197 glycosylation site, were generated by reverse genetics and the
      glycosylation site was retained in MDCK cells. In contrast, all the viruses that
      contained the introduced glycosylation site were unable to grow in eggs and
      rapidly lost the glycosylation site once adapted to grow in eggs. We showed that
      glycosylation affected virus binding to the alpha-2,3-linked sialic acid receptor
      and affected virus antigenicity as tested by postinfected ferret sera. We have
      further identified that the Arginine residue at amino acid position 141 (141R)
      can stabilize the 196/197 glycosylation site without affecting virus
      antigenicity. Thus, the 141R could be introduced into vaccine strains to retain
      the 196/197 glycosylation site for influenza B vaccines.

PMID- 18079026
TI  - Beneficial effects of quetiapine in a transgenic mouse model of Alzheimer's
      disease.
AB  - Previous studies have suggested that quetiapine, an atypical antipsychotic drug,
      may have beneficial effects on cognitive impairment, and be a neuroprotectant in
      treating neurodegenerative diseases. In the present study, we investigated the
      effects of quetiapine on memory impairment and pathological changes in an amyloid
      precursor protein (APP)/presenilin-1 (PS-1) double transgenic mouse model of
      Alzheimer's disease (AD). Non-transgenic and transgenic mice were treated with
      quetiapine (0, 2.5, or 5mg/(kg day)) for 1, 4, and 7 months in drinking water
      from the age of 2 months. After 4 and 7 months of continuous quetiapine
      administration, memory impairment was prevented, and the number of beta-amyloid
      (Abeta) plaques decreased in the cortex and hippocampus of the transgenic mice.
      Quetiapine also decreased brain Abeta peptides, beta-secretase activity and
      expression, and the level of C99 (an APP C-terminal fragment following cleavage
      by beta-secretase) in the transgenic mice. Furthermore, quetiapine attenuated
      anxiety-like behavior, up-regulated cerebral Bcl-2 protein, and decreased
      cerebral nitrotyrosine in the transgenic mice. These findings suggest that
      quetiapine can alleviate cognitive impairment and pathological changes in an
      APP/PS1 double transgenic mouse model of AD, and further indicate that quetiapine
      may have preventive effects in the treatment of AD.

PMID- 18079028
TI  - Soil microorganisms determine the sorption of radionuclides within organic soil
      systems.
AB  - The potential of soil microorganisms to enhance the retention of (137)Cs and
      (85)Sr in organic systems was assessed in a series of experiments. A biologically
      active, 'mineral-free', organic material, produced under laboratory conditions
      from leaves, was used as the uptake matrix in all experiments to minimise
      potential interference from competing clay minerals. Biological uptake and
      release were differentiated from abiotic processes by comparing the sorption of
      radionuclides in sterilised organic material with sterile material inoculated
      with soil extracts or single fungal strains. Our results show conclusively that
      living components of soil systems are of primary importance in the uptake of
      radionuclides in organic material. The presence of soil microorganisms
      significantly enhanced the retention of Cs in organic systems and approximately
      70% of the Cs spike was strongly (irreversibly) bound (remained non-extractable)
      in the presence of microorganisms compared to only approximately 10% in abiotic
      systems. Sorption of (85)Sr was not significantly influenced by the presence of
      soil microorganisms. A non-linear temperature response was observed for the
      retention in biotic systems with increased uptake at between 10 and 30 degrees C
      and lower retention at temperatures above or below the optimum range. The optimum
      temperatures for biological uptake were between 15 and 20 degrees C for Cs, and
      25 and 30 degrees C for Sr. Our results indicate that single strains of soil and
      saprotrophic fungi make an important contribution to the sorption of Cs and Sr in
      organic systems, but can only account for part of the strong, irreversible
      binding observed in biotic systems. Single strains of soil fungi increased the
      amount of non-extractable (137)Cs (by approximately 30%) and (85)Sr (by
      approximately 20%) in the organic systems as compared to abiotic systems, but the
      major fraction of (137)Cs and (85)Sr sorbed in systems inoculated with
      saprotrophic fungi remained extractable.

PMID- 18079029
TI  - Postural balance during quiet standing in patients with total hip arthroplasty
      and surface replacement arthroplasty.
AB  - BACKGROUND: Primary total hip arthroplasty leads to better functional capacities
      but a general weakness of abductor muscles often persists. A larger head
      component may improve the postural balance in the medial-lateral direction. The
      aims of this study are (1) to compare postural stability in patients after total
      hip and surface replacement arthroplasties and (2) to evaluate the effect of the
      biomechanical reconstruction on postural stability. METHODS: Six months post
      surgery, three groups of ten subjects (total hip and surface replacement
      arthroplasties and control) performed quiet standing tasks in both dual and one
      leg stance and a hip abductor muscles strength test. The root-mean-square
      amplitude of centre of pressure and centre of mass displacement in the anterior
      posterior and medial-lateral directions were calculated for dual stance task.
      FINDINGS: Statistical analyses showed greater centre of pressure and centre of
      mass displacement amplitude in the medial-lateral direction during the dual
      stance for the total hip arthroplasty compared to the surface replacement and
      control subjects (P<0.05). All control subjects completed the one leg stance
      compared to nine in the surface replacement and five in the total hip
      arthroplasty group. No statistical difference was found between the groups in the
      hip abductor muscles strength. INTERPRETATION: The better anatomical
      preservation, absence of femoral stem and the larger bearing component could
      account for the return to better postural stability in surface replacement
      patients in comparison to total hip patients. Further studies are needed to
      determine the impact of each of these factors on the postural balance.

PMID- 18079030
TI  - A new intramedullary nailing device for the treatment of femoral shaft fractures:
      a biomechanical study.
AB  - BACKGROUND: The treatment of choice for early mobilization of femoral fractures
      is surgery, which traditionally employs plates and screws or intramedullary
      nails. We examined the biomechanical properties of a new femoral nail system. The
      new intramedullary propping nailing system, made of a stainless-steel alloy,
      consists of a nail shaft, inner rod, tensile screw, end cape and two interlocked
      screws. METHODS: Intramedullary propping nailing biomechanics was compared with
      that of the Grosse and Kempf nail when securing transverse fractures in 10 pairs
      of cadaveric femurs. The axial compressive, bending, torsional stiffness, and
      strain values were calculated. FINDINGS: The intramedullary propping nailing
      system had torsional stiffness (0.50 Nm/ degrees ) and bending stiffness (699.74
      and 670.84 N/mm of lateral and frontal bending, respectively) comparable with the
      Grosse and Kempf nail (0.35 Nm/ degrees , 644.85 and 606.32 N/mm of lateral and
      frontal bending, respectively). Intramedullary propping nailing system produced a
      significantly higher compressive stiffness (1.67 and 1.50 x 10(6) N/mm,
      respectively) than the Grosse and Kempf nail in the medial and anterior aspects
      (0.86 and 1.32x10(6)N/mm, respectively). Although no significance was found in
      comparison with Grosse and Kempf of the strain of each aspect, intramedullary
      propping nailing system yielded a significantly better-distributed strain
      (F=1.007, P=0.401). INTERPRETATION: Biomechanically, the intramedullary propping
      nailing system is safe and able to provide good abutment of the nail to the bone.
      The intramedullary propping nailing system produces a more extensive and tight
      contact between the nail and bone than the application of Grosse and Kempf nail.

PMID- 18079031
TI  - Mobilisation of sediment-associated metals from historical Pb working sites on
      the River Sheaf, Sheffield, UK.
AB  - Spatial and temporal patterns of metal mobilisation from former water-powered, Pb
      working sites in a suburban area of Sheffield (UK) were investigated. Twelve time
      integrated mass flux samplers were strategically deployed over two contrasting
      campaign periods (summer and winter). Suspended sediment samples were
      characterised magnetically and subjected to metal analysis. Metal levels in the
      upper River Sheaf showed a marked spatial and temporal variability. Pb
      concentrations in particular were relatively high (maximum 2132 mg kg(-1)). Their
      distribution tended to reflect the historical contamination of the valley by 17th
      to 19th century industry, especially during summer high discharge conditions. The
      mean suspended sediment Pb concentration (803 mg kg(-1)) exceeds contamination
      guidelines. It is unclear whether ground remediation of one of the seven
      floodplain sites in the catchment has been successful. The river is still
      affected by the legacy of at least two other Pb working sites.

PMID- 18079032
TI  - Subchronic mycotoxicoses in rats. Histopathological changes and modulation of the
      sphinganine to sphingosine (Sa/So) ratio imbalance induced by Fusarium
      verticillioides culture material, due to the coexistence of aflatoxin B1 in the
      diet.
AB  - Mycotoxicoses are diseases caused by consumption of diets contaminated with
      mycotoxins, a special class of fungal secondary metabolites. Fumonisin B1 (FB1)
      and aflatoxin B1 (AFB1), the main toxins synthesized by toxicogenic stocks of
      Fusarium spp. and Aspergillus spp., respectively, can coexist in grains and in
      its by-products. We investigated a probable synergism of a fumonisins-containing
      Fusarium verticillioides culture material and AFB1 in the induction of hepatocyte
      apoptosis in rats subchronically fed on a mixture of them. Furthermore, the
      possibility of modifications in the fumonisins-induced Sa/So ratio imbalance in
      tissues and urine from rats poisoned with this mycotoxin, due to the presence of
      AFB1 in the diet, was evaluated. The co-exposure to fumonisins and AFB1 produced
      a higher liver toxicity, with respect to their individual administration,
      inducing apoptosis and mitotic hepatocytes. There was an inversion of the typical
      Sa/So ratio in rats fed on the culture material as well as in those subjected to
      a diet co-contamined with fumonisins and AFB1. Moreover, the later had a
      synergistic effect in the induction of Sa/So variations in kidneys. Therefore,
      the mixture of fumonisins and AFB1 induced toxic responses which could not be
      considered a sum of the effects caused individually by these mycotoxins.

PMID- 18079033
TI  - Investigations concerning the long term effects of dietary factors on human
      health: current topics, methods and new concepts.

PMID- 18079034
TI  - The effect of two luting agents, pretreatment of the post, and pretreatment of
      the canal dentin on the retention of fiber-reinforced composite posts.
AB  - OBJECTIVES: The purposes of this study were to evaluate the push-out strength of
      core-build-up resin used for fiber-post cementation and to test the effects of
      different post and dentin pretreatment for different regions of the root.
      METHODS: After endodontic treatment 216 human teeth received a glass-fiber post.
      The teeth were divided into test groups to simulate the effects of: (I)
      cementation material (specifically core-build-up resin or conventional luting
      cement), (II) pretreatment of the root dentin (none, dual-curing bonding, light
      curing bonding), (III) pretreatment of the post (none, hydrofluoric acid,
      tribochemical pretreatment), and (IV) different regions of the root. After
      thermal cycling all post-cemented roots were sectioned and each specimen was
      loaded in a universal testing machine until failure occurred. Statistical
      analysis was performed by use of a mixed-effects regression model. RESULTS: The
      cementation material (p<or=0.001), the pretreatment of the post (p<or=0.001), and
      the bonding of the root dentin (p<or=0.001) had a significant effect on mean push
      out strength. Statistical analysis also revealed a significant effect of root
      region (p<or=0.001)-values were lower for the apical region than for the coronal
      third of the root. CONCLUSIONS: Enhanced retention can be achieved by use of a
      core-build-up resin for fiber-post cementation. Tribochemical pretreatment of the
      post and use of a dual-curing bonding system also increased mean push-out
      strength.

PMID- 18079035
TI  - Depressive symptoms and baseline prefrontal EEG alpha activity: a study utilizing
      Ecological Momentary Assessment.
AB  - Prefrontal cortex (PFC) electroencephalography (EEG) alpha asymmetry has been
      found in individuals with major depression. However, EEG activity has never been
      examined in regard to specific depressive symptoms. We examine the relationship
      between resting baseline PFC alpha activity and both rumination and self-esteem
      in a depressed outpatient group (N=6) and a healthy control group (N=7) using
      high-density EEG sampling and multiple longitudinal self report measures, i.e.
      Ecological Momentary Assessment (EMA). Symptom measures were collected five times
      daily for 7 days, i.e. 35 assessments. Using a mixed-level analysis, significant
      Group x Hemisphere interactions for PFC sites and both rumination and self-esteem
      were found. Within the depressed group, lower bilateral PFC activity predicted
      higher levels of rumination, and lower right PFC activity predicted higher levels
      of self-esteem. There were no significant effects for the control group. Results
      indicate that specific symptoms of depression are uniquely associated with
      patterns of PFC EEG alpha activity.

PMID- 18079036
TI  - Pyruvate reduces in vitro the embryotoxic effect of peritoneal fluid from
      infertile women with endometriosis.
AB  - OBJECTIVES: To ascertain the embryotoxicity of peritoneal fluid from infertile
      women with endometriosis (PF-E), on mouse embryos in culture and to examine the
      effect of pyruvate in the culture medium on PF-E induced embryotoxicity. STUDY
      DESIGN: Blood-free peritoneal fluid samples were obtained during laparoscopic
      investigation for infertility from 21 infertile women with endometriosis. The
      severity of endometriosis ranged from minimal or mild (PF-min to mild-E; n=7),
      moderate (PF-mod-E; n=7), to severe (PF-sev-E; n=7). Peritoneal fluid samples
      were centrifuged at 600 x g for 10 min and 4 degrees C, and the supernatant was
      incubated at 56 degrees C for 30 min in a water bath to inactivate the complement
      protein. Mice were super ovulated with intraperitoneal injection (IP) of 5IU of
      pregnant mare serum gonadotrophin and human chorion gonadotrophin. Twenty-four
      hours after confirmation of mating two-cell mouse embryos were obtained. They
      were then cultured in modified Whitten's medium (mWM) with peritoneal fluid from
      patients with endometriosis, and either in the absence or presence of excess
      pyruvate (0.062 mmol(-1)). Embryos were cultured for 72 h. RESULTS AND
      CONCLUSION: Addition of 5% PF-E significantly (p<0.001) suppressed embryo growth
      at 24, 48, and 72 h of culture and the degree of suppression correlated with the
      severity of the disease. The presence of 0.062 mmol(-1) pyruvate in the culture
      medium significantly (p<0.001) reduced the embryotoxicity of PF-min to mild-E and
      PF-mod-E at each stage of development, but was only seen at 24h of culture
      (p<0.001) in cultures with PF-sev-E even when the concentration of pyruvate in
      the medium was increased to 0.31 mmol(-1). This study confirms the embryotoxicity
      of PF-E in vitro, which was reduced by the presence pyruvate in the culture
      medium, particularly in cultures containing fluid from women with endometriosis
      of minimum or mild to moderate severity.

PMID- 18079037
TI  - Embryotoxicity of serum from women smoking cocaine base paste (CBP).
AB  - OBJECTIVE: Using a mouse embryo bioassay, we examined the embryotoxic properties
      of serum obtained from eight women who had ingested cocaine base paste (CBP) for
      a period of 1-3 years. STUDY DESIGN: Two-cell stage mouse embryos were cultured
      in the presence of serum extracted from eight CBP-smoking or control women. After
      48h, embryos were evaluated to determine their developmental stage and then
      processed by Tarkoswki's technique to determine the proportion of embryos with
      micronuclei, in order to establish the number of micronuclei/embryo. RESULTS:
      Serum from CBP patients diminished the percentage of embryos progressing to the
      compacted morula stage, while increasing the proportion of embryos with
      micronuclei and the corresponding micronuclei/embryo ratio. CONCLUSION: These
      findings provide the first experimental evidence of embryotoxic compounds in the
      serum of CBP-smoking women. This study highlights the reproductive risk of
      chronically ingested CBP and demonstrates the need for further studies.

PMID- 18079038
TI  - Learning for sustainability: participatory resource management in Cambodian
      fishing villages.
AB  - Considerable attention is now being given to the role and importance of education
      and learning implications of participatory resource and environmental governance.
      The contention is that such learning has the potential to transform behaviour,
      and in the case of resource management, may help change current patterns in
      resource use towards a more sustainable social-ecological system. Our purpose is
      to establish the opportunities for learning afforded to those participating in
      local level resource management committees in two Cambodian fishing communities
      and consider the learning outcomes from such opportunities. Our approach was
      qualitative and used a case study design. The findings establish a wide range of
      committee resource management activities that resulted in both instrumental
      (e.g., learning about administrative procedures) and communicative (e.g.,
      insights into the need to conserve mangroves) learning. It was revealed that such
      learning can lead to changes in behaviour at the community level (e.g., managing
      local waste). Our findings also indicated a number of motivators and enablers of
      learning such as opportunities for dialogue, leadership and the presence of
      declining resources.

PMID- 18079039
TI  - Predicting land cover using GIS, Bayesian and evolutionary algorithm methods.
AB  - Modelling land cover change from existing land cover maps is a vital requirement
      for anyone wishing to understand how the landscape may change in the future. In
      order to test any land cover change model, existing data must be used. However,
      often it is not known which data should be applied to the problem, or whether
      relationships exist within and between complex datasets. Here we have developed
      and tested a model that applied evolutionary processes to Bayesian networks. The
      model was developed and tested on a dataset containing land cover information and
      environmental data, in order to show that decisions about which datasets should
      be used could be made automatically. Bayesian networks are amenable to
      evolutionary methods as they can be easily described using a binary string to
      which crossover and mutation operations can be applied. The method, developed to
      allow comparison with standard Bayesian network development software, was proved
      capable of carrying out a rapid and effective search of the space of possible
      networks in order to find an optimal or near-optimal solution for the selection
      of datasets that have causal links with one another. Comparison of land cover
      mapping in the North-East of Scotland was made with a commercial Bayesian
      software package, with the evolutionary method being shown to provide greater
      flexibility in its ability to adapt to incorporate/utilise available
      evidence/knowledge and develop effective and accurate network structures, at the
      cost of requiring additional computer programming skills. The dataset used to
      develop the models included GIS-based data taken from the Land Cover for Scotland
      1988 (LCS88), Land Capability for Forestry (LCF), Land Capability for Agriculture
      (LCA), the soil map of Scotland and additional climatic variables.

PMID- 18079040
TI  - The role of satellite and decentralized strategies in water resources management.
AB  - Existing and projected water shortages and related factors have helped focus
      attention on the need for water reuse. With recent technological advances in
      wastewater treatment, it is now possible to produce reclaimed water of any
      quality. Thus, the use of reclaimed water will depend on the reuse opportunities
      and the cost of the required infrastructure. Historically, centralized wastewater
      treatment facilities have served the needs of organized societies since the mid
      1800s. However, as there are limited options for expansion of most existing
      centralized facilities, the use of satellite and decentralized wastewater
      management systems offers significant advantages including being close both to
      the source of wastewater generation and to potential water reuse applications.
      The comparative advantages of satellite and decentralized wastewater management
      systems for a number of water reuse applications are presented and discussed in
      this paper. Selected case studies are presented to demonstrate the utility of
      satellite and decentralized wastewater management. Specific issues associated
      with the application of such systems in existing and in new developments are
      examined and discussed.

PMID- 18079041
TI  - A survey of storm-water management water quality regulations in four Mid-Atlantic
      States.
AB  - This paper examines and compares the management practices and regulatory
      approaches used by the Mid-Atlantic States of Delaware, Maryland, New Jersey, and
      Pennsylvania for improving the quality of storm-water runoff. Such practices
      range from simple extended detention criteria in Pennsylvania through the BMP
      credit system used by Maryland, to the latest "green technology" methods promoted
      in Delaware and the recharge, quality and peak reduction approaches of New
      Jersey. All practices are designed to meet EPA requirements for total suspended
      solids (TSS) removal, but verification of performance is not required. More
      sophisticated methods of evaluating TSS removal that can be used for engineering
      design purposes are needed.

PMID- 18079042
TI  - Susceptibility indexing method for irrigation water management planning:
      applications to K. Menderes river basin, Turkey.
AB  - A susceptibility indexing method was developed based on vulnerability and quality
      indices. The contamination susceptibility index (SI) at a given location was
      calculated by taking the product of the vulnerability index (VI) and the quality
      index (QI): SI=VIxQI. This method incorporates both hydrogeological and
      hydrochemical data for a comprehensive index mapping. The DRASTIC index
      methodology was used for the hydrogeological data evaluations. The quality index
      calculation procedure based on a water quality classification scheme was
      introduced to evaluate hydrochemical data. The suggested susceptibility indexing
      method was applied to the Kucuk Menderes river basin located in western Turkey.
      The susceptibility index map shows both hydrogeological and hydrochemical data
      related to the contamination problem including areas that should be taken into
      consideration during water management planning. The index map indicates that the
      most susceptible groundwater is located along the river channel between Kiraz and
      Tire towns, in the Selcuk area and along the Fertek stream channel to the north
      of Torbali town. The results indicate that the incorporation of both
      hydrogeological and hydrochemical datasets enables more realistic evaluations
      than those of an individual dataset to estimate the groundwater contamination
      susceptibility of an aquifer. The numerical procedure applied could be extended
      further by including other parameters such as retardation, potential contaminant
      sources, etc. that affect the water quality in a given basin.

PMID- 18079043
TI  - Ecolabeled paper towels: consumer valuation and expenditure analysis.
AB  - Ecolabeled paper towels are manufactured using post-consumer recycled material
      and sold in markets using a recycle logo. Environmentally conscious consumers
      purchase these paper towels and thereby contribute to improving environmental
      quality. In this paper, we estimate the implicit value placed by consumers on
      ecolabeled paper towels using a hedonic price function and conduct an expenditure
      analysis using Heckman's selection model. Using the data set from the Internet
      based grocery stores called as Peapod we find that some consumers recognize
      ecolabels on paper towels and place a substantial, positive price premium on
      them. The expenditure analysis indicates that for the preferred functional form,
      the demand for ecolabeled paper towels is inelastic for environmentally conscious
      consumers. The simulated results from the selection model indicate that a small
      subsidy for ecolabeled paper towels will not substantially change consumers'
      purchase decisions.

PMID- 18079044
TI  - In situ removal of copper from sediments by a galvanic cell.
AB  - This study dealt with in situ removal of copper from sediments through an
      electrokinetic (EK) process driven by a galvanic cell. Iron (Fe) and carbon (C)
      were placed separately and connected with a conductive wire. Polluted sediments
      were put between them and water was filled above the sediments. The galvanic cell
      was thus formed due to the different electrode potentials of Fe and C. The cell
      could remove the pollutants in the sediments by electromigration and/or
      electroosmosis. Results showed that a weak voltage less than 1V was formed by the
      galvanic cell. The voltage decreased with the increase of time. A slight increase
      of sediment pH from the anode (Fe) to the cathode (C) was observed. The presence
      of supernatant water inhibited the variation of sediment pH because H(+) and OH(
      ) could diffuse into the water. The removal of copper was affected by the
      sediment pH and the distribution of electrolyte in sediment and supernatant
      water. Lower pH led to higher removal efficiency. More electrolyte in the
      sediment and/or less electrolyte in the supernatant water favored the removal of
      copper. The major removal mechanism was proposed on the basis of the desorption
      of copper from sediment to pore solution and the subsequent electromigration of
      copper from the anode to the cathode. The diffusion of copper from sediment to
      supernatant water was negligible.

PMID- 18079045
TI  - Indoor air quality investigation according to age of the school buildings in
      Korea.
AB  - Since the majority of schools are housed in buildings dating from the 1960s and
      1970s, a comprehensive construction and renovation program of school buildings
      has been carried out to improve the educational conditions in Korea. However,
      classrooms and computer rooms, with pressed wood desks, chairs and furnishings,
      as well as construction materials, might have negative effects on the indoor air
      quality. Furthermore, most schools have naturally ventilated classrooms. The
      purpose of this study was to characterize the concentrations of different indoor
      air pollutants within Korean schools and to compare their indoor levels within
      schools according to the age of school buildings. Indoor and outdoor air samples
      of carbon monoxide (CO), carbon dioxide (CO(2)), particulate matter (PM(10)),
      total microbial count (TBC), total volatile organic compounds (TVOCs) and
      formaldehyde (HCHO) were obtained during summer, autumn and winter from three
      sites; a classroom, a laboratory and a computer classroom at 55 different
      schools. The selection of the schools was based on the number of years since the
      schools had been constructed. The problems causing indoor air pollution at the
      schools were chemicals emitted by building materials or furnishings, and
      insufficient ventilation rates. The I/O ratio for HCHO was 6.32 during the
      autumn, and the indoor HCHO concentrations (mean = 0.16 ppm) in schools
      constructed within 1 year were significantly higher than the Korean Indoor Air
      Standard, indicating that schools have indoor sources of HCHO. Therefore,
      increasing the ventilation rate by means of a mechanical system and the use of
      low-emission furnishings can play key roles in improving the indoor air quality
      within schools.

PMID- 18079046
TI  - Exploring discourses on international environmental regime effectiveness with Q
      methodology: a case study of the Mediterranean Action Plan.
AB  - Extensive research has been done on the 'high politics' of negotiations of
      international environmental agreements. However, little attention has been paid
      to the effectiveness of their implementation after coming into force.
      Effectiveness cannot be easily measured, since different stakeholders use
      different criteria as the basis of their opinion. The purpose of this study is to
      investigate discourses on the effectiveness of an international environmental
      regime. The regime chosen is the Mediterranean Action Plan (MAP) - and its legal
      framework, the Barcelona Convention - which was established in 1975 under the
      aegis of the United Nations Environment Programme (UNEP). Q methodology was used
      to reveal discourses on the effectiveness of UNEP/MAP. After collecting relevant
      literature and identifying the stakeholders, 25 in-depth interviews were
      conducted. The stakeholders were from the Secretariat of the Convention,
      academia, NGO workers, and others that studied or knew the subject well. From
      these interviews 294 statements were extracted, from which 44 were finally
      selected to be used in the Q study. The interviewees were approached for the
      second time to complete the Q sorts. This study revealed four distinct discourses
      concerning the effectiveness of international environmental regimes. It concludes
      that there is no one 'right' way of defining effectiveness and that no approach
      can provide more than a partial evaluation of the overall effectiveness of a
      regime.

PMID- 18079047
TI  - Traffic mortality and the role of minor roads.
AB  - Roads have large impacts on wildlife, as they form one of the principal causes of
      mortality, and disturbance and fragmentation of habitat. These impacts are mainly
      studied and mitigated on major roads. It is, however, a widespread misconception
      that most animals are killed on major roads. In this paper, we argue that minor
      roads have a larger impact on wildlife with respect to habitat destruction, noise
      load and traffic mortality. We use data on traffic related deaths in badgers
      (Meles meles) in The Netherlands to illustrate that traffic mortality is higher
      on minor roads. We ask for a more extensive investigation of the environmental
      impacts of minor roads. Moreover, we argue that the success of mitigation on
      roads drastically increases when both major and minor roads are integrated in the
      planning of traffic flows. Therefore, we propose a strategy based on the concept
      of a "traffic-calmed area". Traffic-calmed areas create opportunities for
      wildlife by decreasing limitations for animal movement. We ask for further
      studies to estimate what size traffic-calmed areas should be to maintain minimum
      viable animal populations.

PMID- 18079048
TI  - Influence of vegetation on the removal of heavy metals and nutrients in a
      constructed wetland.
AB  - A free water surface wetland was built to treat wastewater containing metals (Cr,
      Ni, Zn) and nutrients from a tool factory in Argentina. Water, sediment and
      macrophytes were sampled in the inlet and outlet area of the constructed wetland
      during three years. Three successive phases of vegetation dominance were
      developed and three different patterns of contaminant retention were observed.
      During the Eichhornia crassipes dominance, contaminants were retained in the
      macrophyte biomass; during the E. crassipes+Typha domingensis stage, contaminants
      were retained in the sediment and in the T. domingensis dominance stage,
      contaminants were retained in sediment and in the macrophyte biomass. Removal
      efficiency was not significantly different among the three vegetation stages,
      except for NH(4)(+) and i-P(diss). Because of its highest tolerance, T.
      domingensis is the best choice to treat wastewater of high pH and conductivity
      with heavy metals, a common result from many industrial processes.

PMID- 18079049
TI  - Biodiversity on Swedish pastures: estimating biodiversity production costs.
AB  - This paper estimates the costs of producing biological diversity on Swedish
      permanent grasslands. A simple model is introduced where biodiversity on pastures
      is produced using grazing animals. On the pastures, the grazing animals create a
      sufficient grazing pressure to lead to an environment that suits many rare and
      red-listed species. Two types of pastures are investigated: semi-natural and
      cultivated. Biological diversity produced on a pasture is estimated by combining
      a biodiversity indicator, which measures the quality of the land, with the size
      of the pasture. Biodiversity is, in this context, a quantitative measure where a
      given quantity can be produced either by small area with high quality or a larger
      area with lower quality. Two areas in different parts of Sweden are investigated.
      Box-Cox transformations, which provide flexible functional forms, are used in the
      empirical analysis and the results indicate that the biodiversity production
      costs differ between the regions. The major contribution of this paper is that it
      develops and tests a method of estimating biodiversity production costs on
      permanent pastures when biodiversity quality differs between pastures. If the
      method were to be used with cost data, that were more thoroughly collected and
      covered additional production areas, biodiversity cost functions could be
      estimated and used in applied policy work.

PMID- 18079050
TI  - Screening for prostate cancer in 2007: the PSA era and its challenges are not
      over.

PMID- 18079051
TI  - Contribution of a single repeat PSA test to prostate cancer risk assessment:
      experience from the ProtecT study.
AB  - OBJECTIVE: To examine whether a single repeat prostate-specific antigen (PSA)
      helps discriminate cancer from non-cancer-related PSA elevation. METHODS: Men
      aged 50-70 yr (n=54,087) in a multicentre randomised controlled trial comparing
      treatments for localised prostate cancer were tested. A total of 4102 (7.6%) with
      an initial PSA in the range of 3-19.9 ng/ml had repeat measurement (median
      interval: 50 d) followed by prostate biopsy. The decision to biopsy was based on
      the first PSA level. The outcome was the presence of prostate cancer on biopsy.
      RESULTS: Men with a 20% drop in PSA had a lower risk of cancer (odds ratio
      [OR]=0.43; 95% confidence interval [CI], 0.35-0.52; p<0.001) and high-grade
      cancer (OR=0.29; 95%CI, 0.19-0.44; p<0.001) compared to the rest of the cohort.
      The effect of percentage reduction was greater in men aged < or =60 yr than in
      those >60 yr. (OR for any cancer=1.6; 95%CI, 1.0-2.4; p=0.05; OR for high-grade
      cancer=2.9; 95%CI, 1.2-6.7; p=0.014). This equated to a risk reduction of high
      grade cancer from 4% to 0.5%, 6% to 2%, and 15% to 2% in men < or =60 yr with an
      initial PSA of 3.0-3.99, 4.0-5.99, and > or =6 ng/ml, respectively. No level of
      repeat PSA confidently predicted absence of cancer. CONCLUSION: Following an
      initial PSA of 3.0-19.99 ng/ml in men aged 50-70 yr, repeat PSA within 7 wk
      allows more accurate risk prediction that may assist in the decision-making as to
      whether or not to proceed with prostate biopsy.

PMID- 18079052
TI  - Vitamin D receptor polymorphisms and risk of epithelial ovarian cancer.
AB  - The vitamin D receptor (VDR) is a critical mediator of the cellular effects of
      vitamin D. The associations between four common VDR polymorphisms (BSMI, APAI,
      TAQI, and FOKI) and risk of epithelial ovarian cancer (EOC) were assessed in a
      case-control study nested within two prospective cohorts. One hundred seventy
      incident cases of EOC and 323 individually matched controls were genotyped.
      Overall, no associations were observed in genotype analyses. Haplotypes combining
      three SNPs in high linkage disequilibrium (BSMI, APAI, and TAQI) were also not
      associated with risk. These observations do not support a role for BSMI, APAI,
      TAQI, and FOKI polymorphisms in epithelial ovarian cancer in a predominantly
      Caucasian population.

PMID- 18079053
TI  - Coding region polymorphisms in the CHFR mitotic stress checkpoint gene are
      associated with colorectal cancer risk.
AB  - CHFR was recently identified as an early mitotic checkpoint that delays
      transition to metaphase in response to mitotic stress. Although studies have
      shown that CHFR is relevant to tumorigenesis, no previous report has investigated
      whether polymorphisms in the CHFR gene are associated with the risk of cancer
      development. Here, we genotyped polymorphisms in the CHFR gene and analyzed the
      possible associations of single polymorphisms and haplotypes with the risk and
      clinicopathological characteristics of colorectal cancer. Six coding SNPs in the
      CHFR gene were genotyped in 462 colorectal cancer patients and 245 healthy normal
      controls, using either the TaqMan assay or direct sequencing. Our results
      revealed that the V539M polymorphism was significantly associated with a lower
      risk of colorectal cancer (P=0.03; OR, 0.533; 95% CI, 0.302-0.94), and
      significantly correlated with no distant metastasis (M0 stage), different TNM
      stage, and microsatellite instability (MSI) among the colorectal cancer patients.
      Among the five tested haplotypes, hap 10 (TGACTA) was significantly associated
      with a lower risk of colorectal cancer (P=0.017; OR, 0.496; 95% CI, 0.279-0.883),
      and colorectal cancer patients carrying this haplotype showed no distant
      metastasis, different TNM stage, and microsatellite instability at a
      significantly higher frequency. These results reveal for the first time that
      polymorphisms in the CHFR gene are associated with colorectal cancer
      susceptibility.

PMID- 18079054
TI  - Integrated bacterial process for the treatment of a spent nickel catalyst.
AB  - Integrated biological processes involving the dissolution and subsequent
      precipitation have been used for the treatment of the spent material from the
      hydrogenation of vegetable oil containing a high-level of nickel. Our results
      show that nickel was successfully leached using Acidithiobacillus thiooxidans.
      The percentages of nickel leached using A. thiooxidans were higher than those
      obtained with dilute sulphuric acid solutions. Due to the physical
      characteristics of the residue, the best results were obtained when the leaching
      process was carried out using sulphuric acid biogenerated by an A. thiooxidans
      biofilm. The recovery of nickel from the leachates was performed at room
      temperature by precipitating with sulphide generated by Desulfovibrio cells.
      Indirect precipitation using sulphide generated in Desulfovibrio sp. cultures
      allowed the recovery of nickel as the very insoluble nickel sulphide.

PMID- 18079055
TI  - Grape bagasse as an alternative natural adsorbent of cadmium and lead for
      effluent treatment.
AB  - This work investigated the utilization of grape bagasse as an alternative natural
      adsorbent to remove Cd(II) and Pb(II) ions from laboratory effluent. X-ray
      diffractometry, Fourier transform infrared spectroscopy, scanning electron
      microscopy, nuclear magnetic resonance, thermogravimetric analyses, surface
      analysis, porosity and porous size were used for characterization of the
      material. Batch experiments were carried out to evaluate the adsorption capacity
      of the material. Parameters such as adsorption pH and contact time were optimized
      for the maximum accumulation onto the solid surface. The pH values found were 7
      and 3 for Cd(II) and Pb(II), respectively, and contact time was 5 min for both
      metals. Adsorption capacity for metals were calculated from adsorption isotherms
      by applying the Langmuir model and found to be 0.774 and 0.428 mmol g(-1) for
      Cd(II) and Pb(II), respectively. The competition between metals for the same
      adsorption sites on grape bagasse was also evaluated, showing an increasing
      affinity for Pb(II) over Cd(II) when only these metals are present. The potential
      of this material was demonstrated by efficient metal removal from laboratory
      effluent using a glass column. The results indicate that the referred material
      could be employed as adsorbent for effluent treatment, especially due to its easy
      acquisition and low cost as well as the fast adsorption involved.

PMID- 18079057
TI  - Screening level fish community risk assessment of chemical warfare agents in the
      Baltic Sea.
AB  - Chemical warfare agents (CWAs) have been disposed of in various fashions over the
      past decades. Significant amounts (approximately 11,000 tonnes) have been dumped
      in the Baltic Sea east of the island Bornholm following the disarmament of
      Germany after World War II, causing concerns over potential environmental risks.
      Absence of risk based on assumptions of extremely low solubility of CWAs cannot
      alone dismiss these concerns. Existing and modelled fate and effects data were
      used in the analysis to assess the fish community risk level. The most realistic
      and also conservative assessment result is the scenario describing 70 m water
      depth for the most realistic dump-site area with a focus on chronic toxicity, at
      0-20 cm above the sediment, yielding a total mixture toxic unit (TU) of 0.62.
      Triphenylarsine is the CWA with the highest realistic risk profile at 0.2 TU for
      the fish community followed by Adamsite (0.17), Clark I (0.086) and Yperite
      (0.083) TU. Adamsite is more persistent and constitutes a potential risk for a
      longer period than triphenylarsine. The seawater volume potentially at risk is <4
      m above sediment and <58 km down current of dump sites. Further risk assessment
      of dumped CWAs in the Baltic Sea is warranted.

PMID- 18079056
TI  - Pentachlorophenol removal from water using surfactant-enhanced filtration through
      low-pressure thin film composite membranes.
AB  - Removal of pentachlorophenol from water is investigated using the surfactant
      enhanced cross-flow membrane filtration technique in which anionic surfactant;
      sodium dodecyl sulfate (SDS) is the carrier of pentachlorophenol. The separation
      performances are studied by varying SDS concentrations (<<critical micelle
      concentration, CMC). The association between pentachlorophenol and SDS leads to
      increase their effective size of the feed solutes and thus results the
      improvement in separation performances of the membrane. The performance is co
      related with the separation of markers (glucose and sucrose) as well as salt
      rejection of the membrane. SDS, in feed induces the charge due to its polar head
      and thus separation improves due to electrostatic repulsion of membrane and
      associated molecule. The higher hydrophobicity of pentachlorophenol is also the
      factor. The study reveals that there is better improvement in pentachlorophenol
      separation upon addition of SDS for the thin film composite membrane which is of
      more permeability.

PMID- 18079058
TI  - Downregulation of glutamate transporters is associated with elevation in
      extracellular glutamate concentration following rat microsphere embolism.
AB  - Sodium-dependent glutamate transporters expressed in astroglial cells and neurons
      are essential for clearance of extracellular glutamate. In the present study, we
      found elevation of extracellular glutamate concentration associated with
      concomitant downregulation of glutamate transporters following rat microsphere
      embolism (ME). A marked increase in extracellular glutamate in the rat striatum
      was observed by microdialysis immediately after ME induction, and glutamate
      remained elevated at least 12h after ischemia. Concomitantly, impairment of high
      KCl (146 mM)-induced glutamate release was observed in the striatum 12h after ME.
      Consistent with the persistent increase in extracellular glutamate, expression of
      the glutamate transporters EAAC1 and GLT-1 significantly decreased 6h after
      insult without a change in GLAST levels. GLT-1 expression was restored to basal
      levels within 48 h, whereas EAAC1 expression remained decreased up to at least 72
      h after ME. Restoration of GLT-1 was associated with increased expression of the
      astroglial marker GFAP, whereas markedly reduced EACC1 levels were correlated
      with reduced levels of the neuronal marker MAP2, likely due to loss of vulnerable
      neurons. Taken together, downregulation of glutamate transporters after ME is
      associated with dysregulation of basal glutamate concentrations and KCl-induced
      glutamate release in the brain.

PMID- 18079059
TI  - Evidence of reciprocal connections between the dorsal raphe nucleus and the
      retina in the monkey Cebus apella.
AB  - Possible connections between the retina and the raphe nuclei were investigated in
      the monkey Cebus apella by intraocular injection of cholera toxin B subunit
      (CTb). CTb-positive fibers were seen in the lateral region of the dorsal raphe
      nucleus (DR) on the side contralateral to the injection, and a few labeled
      perikarya were observed in the lateral portion of the DR on the ipsilateral side.
      Our findings suggest that direct and reciprocal connections between the retina
      and DR may exist in Cebus apella. These connections might be part of an important
      pathway through which the light/dark cycle influences the activity and/or
      functional status of raphe neurons, with potential effects on a broad set of
      neural and behavioral circuits.

PMID- 18079060
TI  - Intolerance of uncertainty correlates with insula activation during affective
      ambiguity.
AB  - Intolerance of uncertainty (IU), or the increased affective response to
      situations with uncertain outcomes, is an important component process of anxiety
      disorders. Increased IU is observed in panic disorder (PD), obsessive compulsive
      disorder (OCD) and generalized anxiety disorder (GAD), and is thought to relate
      to dysfunctional behaviors and thought patterns in these disorders. Identifying
      what brain systems are associated with IU would contribute to a comprehensive
      model of anxiety processing, and increase our understanding of the neurobiology
      of anxiety disorders. Here, we used a behavioral task, Wall of Faces (WOFs),
      during functional magnetic resonance imaging (fMRI), which probes both affect and
      ambiguity, to examine the neural circuitry of IU in 14 (10 females) college age
      (18.8 years) subjects. All subjects completed the Intolerance of Uncertainty
      Scale (IUS), Anxiety Sensitivity Index (ASI), and a measure of neuroticism (i.e.
      the NEO-N). IUS scores but neither ASI nor NEO-N scores, correlated positively
      with activation in bilateral insula during affective ambiguity. Thus, the
      experience of IU during certain types of emotion processing may relate to the
      degree to which bilateral insula processes uncertainty. Previously observed
      insula hyperactivity in anxiety disorder individuals may therefore be directly
      linked to altered processes of uncertainty.

PMID- 18079061
TI  - Norepinephrine-induced nociception and vasoconstrictor hypersensitivity in rats
      with chronic post-ischemia pain.
AB  - Painful hypersensitivity to norepinephrine (NE) has been reported in various
      chronic pain conditions that exhibit sympathetically-maintained pain (SMP),
      particularly CRPS-I and II. We investigated the parallels between the nociceptive
      and vascular sensitivity to NE in rats with chronic post-ischemia pain (CPIP), an
      animal model of CRPS-I induced by hind paw ischemia-reperfusion injury.
      Intradermal injections of NE to the affected hind paw induced dose-dependent
      nociceptive behaviours in CPIP rats, but not sham animals. These behaviours were
      blocked by alpha(1)- and alpha(2)-adrenergic receptor antagonists, or a nitric
      oxide (NO) donor. Using laser Doppler flowmetry, we detected vasoconstrictor
      hypersensitivity in the ipsilateral CPIP hind paw, as compared to responses in
      sham animals or the contralateral hind paw. The vasoconstrictor hypersensitivity
      was also attenuated by adrenergic antagonists. Intradermal injection of [Arg(8)]
      vasopressin (AVP) or the endothelial NO synthase (eNOS) inhibitor, L-NIO, to the
      affected paw also induced nociceptive behaviours in CPIP rats, but not sham rats.
      These results suggest CPIP rats display abnormal nociceptive responses to
      adrenergic and non-adrenergic vasoconstrictive agents. Furthermore, the
      nociceptive responses to NE in CPIP rats are paralleled by enhanced
      vasoconstrictive responses to NE, and are relieved by alpha-adrenergic
      antagonists or a vasodilator. We conclude that persistent tissue ischemia and
      hypersensitivity to sympathetic vasoconstriction are important mechanisms for
      pain in CPIP rats, and that either reducing vasoconstriction or enhancing
      vasodilatation may be effective methods of relieving the pain of CRPS-I.

PMID- 18079062
TI  - Prediction of chronic post-operative pain: pre-operative DNIC testing identifies
      patients at risk.
AB  - Surgical and medical procedures, mainly those associated with nerve injuries, may
      lead to chronic persistent pain. Currently, one cannot predict which patients
      undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized
      that the endogenous analgesia system is key to determining the pattern of
      handling noxious events, and therefore testing diffuse noxious inhibitory control
      (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain
      (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain
      reduction during exposure to another noxious stimulus at remote body area), were
      conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy.
      Logistic regression revealed that pre-operatively assessed DNIC efficiency and
      acute post-operative pain intensity were two independent predictors for CPTP.
      Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI,
      p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the
      chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80
      (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain
      for each 10-point increase. The other psychophysical measures, pain thresholds
      and supra-threshold pain magnitudes, did not predict CPTP. For prediction of
      acute post-operative pain intensity, DNIC efficiency was not found significant.
      Effectiveness of the endogenous analgesia system obtained at a pain-free state,
      therefore, seems to reflect the individual's ability to tackle noxious events,
      identifying patients 'at risk' to develop post-intervention chronic pain.
      Applying this diagnostic approach before procedures that might generate pain may
      allow individually tailored pain prevention and management, which may
      substantially reduce suffering.

PMID- 18079063
TI  - Psychometric properties of the Beck Depression Inventory--second edition (BDI-II)
      in individuals with chronic pain.
AB  - Given the high prevalence of depression in individuals with chronic pain and the
      negative outcomes associated with such comorbidity, the importance of assessing
      depressive symptoms is widely acknowledged by chronic pain specialists. The BDI
      II is a commonly employed measure of depressive symptomatology at pain centres;
      however, little is known about its psychometric properties in this population.
      This study evaluated factorial validity, internal consistency, and gender
      invariance of the BDI-II in 481 patients with chronic pain. Four competing models
      of the BDI-II factor structure were examined and confirmatory factor analysis
      supported the conceptualization of depression as a singular latent construct,
      within a hierarchical factor structure consisting of three first-order factors-
      Negative Attitude, Performance Difficulty, and Somatic Elements. Factor
      structure, item-total correlations, and correlations between subscale means and
      subjective pain experience support the inclusion of somatic items despite
      concerns regarding their overlap with pain symptoms. Internal consistency was
      good. Mean total scores were in the moderately severe range. Given the evidence
      of partial measurement invariance, an examination of mean gender differences was
      warranted. In contrast to the general population, the average scores of women and
      men were similar. Overall, results support the construct validity and internal
      consistency of the BDI-II for assessing depressive symptoms in both women and men
      with chronic pain. Results support the appropriateness of computing a total score
      and/or subscale scores. These results impact chronic pain researchers and
      clinicians, particularly given current trends toward empirically supported
      assessment.

PMID- 18079064
TI  - Vector-borne infections in cats: molecular study in Barcelona area (Spain).
AB  - Previous serological surveys have reported the presence of different organisms in
      cats from Spain but little reports exist about the exact identity of these
      organisms. The purpose of the study reported here was to assess the presence of
      DNA of several vector-borne infections in a population of cats from Barcelona
      area. One hundred blood samples obtained from cats admitted to the UAB-VTH were
      entered into the study and classified as healthy (n=48) or unhealthy (n=52). EDTA
      blood samples were assayed for Leishmania infantum, Ehrlichia spp., Anaplasma
      spp., Rickettsia spp., Bartonella spp., Hepatozoon spp., Babesia spp. and
      Theileria spp. DNA by means of PCR amplification and amplicons obtained were
      sequenced. Prevalence of infectious agents found were Leishmania infantum (3%),
      Ehrlichia/Anaplasma sp. (1%), Hepatozoon felis (4%) and Bartonella clarridgeiae
      (1%). Cats being less than 5 years old had more probability of having at less one
      PCR positive result (P=0.028). The results of this study show a low prevalence of
      several vector-borne pathogens among cats from Barcelona area. Although higher
      feline seroprevalences are previously reported, they evidenced exposure and
      probably overestimate the real or active degree of infection. However, it is
      important to maintain a high index of suspicion on these infectious diseases,
      both in sick and asymptomatic cats, and molecular techniques could aid in the
      identification of these pathogens.

PMID- 18079065
TI  - Comparison of three immunodiagnostic tests for experimental Heterophyes
      heterophyes infection in dogs.
AB  - The aim of this study was to compare the performance of three in-house diagnostic
      tests, i.e. counter current immunoelectrophoresis (CCIE), intradermal (ID) and
      indirect fluorescent immunoassay (IFI), for the diagnosis of Heterophyes
      infection. One hundred and twenty puppies were randomly divided into eight groups
      (n=15/group). Heterophyes heterophyes infections were established in these
      puppies by administering a dose of 50 H. heterophyes encysted metacercariae/puppy
      by gavage. Forty puppies of similar age and sex were divided into eight groups,
      of five puppies each and were used as negative controls. Sera pooled from
      separate infected and uninfected groups were tested against H. heterophyes
      antigens, weekly for 8 weeks post-infection (PI). The ID assay detected infected
      puppies sooner than any of the serological tests. Sero-conversion was first
      detected 2 weeks PI by ID assay and 1 week later by CCIE and IFI assays. ID test
      performed well till the end of the experiment (sensitivity and specificity: 100%
      and 90%, respectively). Both IFI and CCIE assays had a sensitivity of 40% and
      20%, respectively for early detection of antibody, which was less sensitive than
      ID but both assays were more specific (100%) than the ID assay. The lowest
      agreement was between ID and IFI tests (40.3%), whilst the highest was observed
      between CCIE and IFI tests (67.2%). Of the three evaluated methods, the ID test
      could be recommended for scientific and laboratory diagnosis of heterophyosis in
      naturally infected animals. However, since none of the investigated method are
      optimal (i.e, offers 100% specificity and sensitivity), the choice of test
      employed must depend on the aim of the study.

PMID- 18079066
TI  - Analysis of the anxiolytic-like effect of TRH and the response of amygdalar
      TRHergic neurons in anxiety.
AB  - Thyrotropin-releasing hormone (TRH) was first described for its neuroendocrine
      role in controlling the hypothalamus-pituitary-thyroid axis (HPT). Anatomical and
      pharmacological data evidence its participation as a neuromodulator in the
      central nervous system. Administration of TRH induces various behavioural effects
      including arousal, locomotion, analepsy, and in certain paradigms, it reduces
      fear behaviours. In this work we studied the possible involvement of TRHergic
      neurons in anxiety tests. We first tested whether an ICV injection of TRH had
      behavioural effects on anxiety in the defensive burying test (DBT).
      Corticosterone serum levels were quantified to evaluate the stress response and,
      the activity of the HPT axis to distinguish the endocrine response of TRH
      injection. Compared to a saline injection, TRH reduced cumulative burying, and
      decreased serum corticosterone levels, supporting anxiolytic-like effects of TRH
      administration. The response of TRH neurons was evaluated in brain regions
      involved in the stress circuitry of animals submitted to the DBT and to the
      elevated plus maze (EPM), tests that allow to correlate biochemical parameters
      with anxiety-like behaviour. In the DBT, the response of Wistar rats was compared
      with that of the stress-hypersensitive Wistar Kyoto (WKY) strain. Behavioural
      parameters were analysed in recorded videos. Animals were sacrificed 30 or 60min
      after test completion. In various limbic areas, the relative mRNA levels of TRH,
      its receptors TRH-R1 and -R2, and its inactivating ectoenzyme pyroglutamyl
      peptidase II (PPII), were determined by RT-PCR, TRH tissue content by
      radioimmunoassay (RIA). The extent of the stress response was evaluated by
      measuring the expression profile of CRH, CRH-R1 and GR mRNA in the
      paraventricular nucleus (PVN) of the hypothalamus and in amygdala, corticosterone
      levels in serum. As these tests demand increased physical activity, the response
      of the HPT axis was also evaluated. Both tasks increased the levels of serum
      corticosterone. WKY rats showed higher anxiety-like behaviour in the DBT than
      Wistar, as well as increased PVN mRNA levels of CRH and GR. TRH mRNA levels
      increased in the PVN and TSH values remained unchanged in both strains although
      TRH content decreased in the medial basal hypothalamus of Wistar rats only. TRH
      content was measured in several limbic regions but only amygdala showed specific
      task-related changes after DBT exposure of both strains: increased TRH content.
      Expression of TRH mRNA decreased in the amygdala of Wistar, suggesting inhibition
      of TRHergic neuronal activity in this region. The participation of amygdalar TRH
      neurons in anxiety was confirmed in the EPM where TRH expression and release
      correlated with the number of entries, and the % of time spent in open arms,
      supporting an anxiolytic role of these TRH-neurons. These results contribute to
      the understanding of the involvement of TRH during emotionally charged situations
      and shed light on the participation of particular circuits in related behaviours.

PMID- 18079067
TI  - Genetic evaluation of the serotonergic system in chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown etiology
      with no known lesions, diagnostic markers or therapeutic intervention. The
      pathophysiology of CFS remains elusive, although abnormalities in the central
      nervous system (CNS) have been implicated, particularly hyperactivity of the
      serotonergic (5-hydroxytryptamine; 5-HT) system and hypoactivity of the
      hypothalamic-pituitary-adrenal (HPA) axis. Since alterations in 5-HT signaling
      can lead to physiologic and behavioral changes, a genetic evaluation of the 5-HT
      system was undertaken to identify serotonergic markers associated with CFS and
      potential mechanisms for CNS abnormality. A total of 77 polymorphisms in genes
      related to serotonin synthesis (TPH2), signaling (HTR1A, HTR1E, HTR2A, HTR2B,
      HTR2C, HTR3A, HTR3B, HTR4, HTR5A, HTR6, and HTR7), transport (SLC6A4), and
      catabolism (MAOA) were examined in 137 clinically evaluated subjects (40 CFS, 55
      with insufficient fatigue, and 42 non-fatigued, NF, controls) derived from a
      population-based CFS surveillance study in Wichita, Kansas. Of the polymorphisms
      examined, three markers (-1438G/A, C102T, and rs1923884) all located in the 5-HT
      receptor subtype HTR2A were associated with CFS when compared to NF controls.
      Additionally, consistent associations were observed between HTR2A variants and
      quantitative measures of disability and fatigue in all subjects. The most
      compelling of these associations was with the A allele of -1438G/A (rs6311) which
      is suggested to have increased promoter activity in functional studies. Further,
      in silico analysis revealed that the -1438 A allele creates a consensus binding
      site for Th1/E47, a transcription factor implicated in the development of the
      nervous system. Electrophoretic mobility shift assay supports allele-specific
      binding of E47 to the A allele but not the G allele at this locus. These data
      indicate that sequence variation in HTR2A, potentially resulting in its enhanced
      activity, may be involved in the pathophysiology of CFS.

PMID- 18079069
TI  - Raised venous pressure as a factor in multiple sclerosis.
AB  - It is hypothesised that the inflammatory condition seen in MS and the progressive
      myelopathy that is being successfully halted by obliteration of dural
      arteriovenous fistulas (DAVFs), may actually be two sides of the same coin.
      Excessive venous hypertension can stretch vein walls sufficiently to separate the
      tight junctions between endothelial cells forming the blood-brain-barrier (BBB).
      Colloids, etc., but not necessarily erythrocytes, could then pass through the
      exposed porous basement membranes. The resulting changes in osmotic pressure,
      etc. would disrupt the axon and dendrite internal transport systems, leading to
      their disintegration. The normal inflammatory processes which would follow, might
      be indistinguishable from those associated with autoimmune disease. Ascending
      progressive myelopathy and disablement are associated with an intracranial DAVF
      when its outflow enters the spinal venous system and descends past the cervical
      region. This can be arrested, and some degree of recovery produced, if the DAVF
      can be successfully eliminated or blocked. However, if the DAVF outflow is
      entirely into the spine, intracranial venous pressure may be normal and so there
      is nothing to alert the clinician to the presence of an intracranial DAVF. It is
      suggested that where spinal MS has been diagnosed from clinical observations,
      patients should be referred for angiological investigation to search for DAVFs
      within the head to identify any treatable subjects.

PMID- 18079068
TI  - A double blind, placebo-controlled trial that combines disulfiram and naltrexone
      for treating co-occurring cocaine and alcohol dependence.
AB  - BACKGROUND: This is a double blind, placebo-controlled trial that evaluated the
      efficacy of disulfiram, naltrexone and their combination in patients with co
      occurring cocaine and alcohol dependence. METHODS: 208 patients were randomized
      to disulfiram (250 mg/day), naltrexone (100 mg/day), the combination, or placebo
      for 11 weeks. Outcomes were in-trial abstinence from cocaine and/or alcohol.
      RESULTS: Few safety concerns were reported, although medication adherence was low
      in a number of patients for both medications, alone or in combination. In the
      primary analyses (GEE modeling), abstinence from cocaine as measured by cocaine
      negative urines and days of self-reported abstinence from cocaine or alcohol did
      not differ between placebo and any of the medication groups. However, patients
      taking disulfiram (alone or in combination) were most likely to achieve combined
      abstinence from cocaine and alcohol. Secondary analyses revealed that patients
      taking the disulfiram-naltrexone combination were most likely to achieve 3
      consecutive weeks of abstinence from cocaine and alcohol. CONCLUSION: There was
      an association between disulfiram treatment and abstinence from cocaine and
      alcohol. More patients taking the disulfiram-naltrexone combination achieved 3
      consecutive weeks of abstinence in treatment than placebo-treated patients.

PMID- 18079070
TI  - Expression of apoptotic and cell proliferation regulatory proteins in
      keratoacanthomas and squamous cell carcinomas of the skin.
AB  - The aim of this study was to investigate the expression of p53, caspase-3, bcl-2,
      MIB-1, and PCNA to validate more objective methods to differentiate squamous cell
      carcinoma and keratoacanthoma, as well as to understand their pathogenesis with
      accuracy. A total of 52 cases of histopathologically diagnosed keratoacanthoma in
      the proliferative stage and 56 cases of well-differentiated squamous cell
      carcinoma were selected in this study. The expression was evaluated by means of
      immunohistochemistry. Bcl-2 immunoreactivity was weak or absent in the majority
      of cases, either in squamous cell carcinoma or in keratoacanthoma. PCNA-positive
      cells did not show differences between two lesions evaluated. On the other hand,
      MIB-1 was statistically significant (p<0.05) between squamous cell carcinomas and
      keratoacanthomas. Moreover, p53 and caspase-3 were overexpressed in squamous cell
      carcinomas. Together, these results suggest that the biological behavior of the
      well-differentiated squamous cell carcinomas of the skin may be associated with
      cellular proliferation and/or deregulation of cell death, indicated by increased
      expression of the MIB-1 and apoptotic proteins p53 and caspase-3, respectively.

PMID- 18079071
TI  - Learning strategies in matching to sample: if-then and configural learning by
      pigeons.
AB  - Pigeons learned a matching-to-sample task with a split training-set design in
      which half of the stimulus displays were untrained and tested following
      acquisition. Transfer to the untrained displays along with no novel-stimulus
      transfer indicated that these pigeons learned the task (partially) via if-then
      rules. Comparisons to other performance measures indicated that they also
      partially learned the task via configural learning (learning the gestalt of the
      whole stimulus display). Differences in the FR-sample requirement (1 vs. 20) had
      no systematic effect on the type of learning or level of learning obtained.
      Differences from a previous study [Wright, A.A., 1997. Concept learning and
      learning strategies. Psychol. Sci. 8, 119-123] are discussed, including the
      effect of displaying the stimuli vertically (traditional display orientation) or
      horizontally from the floor.

PMID- 18079072
TI  - Differential binding of cytokines to environmentally relevant particles: a
      possible source for misinterpretation of in vitro results?
AB  - Inflammation is considered as a key event in adverse health effects associated
      with exposure to ambient particulate matter. The inflammatory potential of
      particles is often compared using in vitro cell systems, where the particle
      induced release of pro-inflammatory cytokines is measured. A major concern in
      these assays is the potential of particles to bind cytokines, which may lead to
      an underestimation of the inflammatory potential. We therefore investigated the
      cytokine binding to a selection of particle samples, including particles
      collected from outdoor sources (wood combustion, traffic) and particles commonly
      used to model environmental sources (ultrafine carbon black, diesel, quartz), for
      a range of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8).
      Furthermore, the influence of serum proteins and particle- and cytokine
      concentrations on the cytokine binding was studied. Cytokines primarily bound to
      carbonaceous particles (up to 85%), not to mineral particles. Furthermore,
      depending on the type of cytokine, the cytokine binding could be reduced partly
      or completely by adding serum proteins to the cell growth medium or particle
      suspensions. Based on these observations we recommend either to adjust culturing
      and exposure conditions to prevent cytokine binding, or to adjust the measured
      cytokine release by application of correction factors obtained from cytokine
      binding experiments.

PMID- 18079073
TI  - The knowledge of osteoporosis risk factors in a Greek female population.
AB  - OBJECTIVES: The social and economic burden of osteoporosis is important since it
      concerns a continuously aging population, while the disease is silent until the
      emergence of fractures. Aim of the study was to assess female population
      knowledge about osteoporosis risk factors and to identify the risk factors of the
      studied population. METHODS: A sample of 99 (aged: 61.59+/-9.61 years) women
      under treatment for osteoporosis or osteopenia answered the questionnaire
      provided by their pharmacists and were included in the study's analysis. Various
      parameters on osteoporosis awareness and risk factor knowledge of the population
      sample studied were analyzed. RESULTS: It was revealed that 96% of the
      participants knew osteoporosis definition and sources of this knowledge were one
      or more of the following: doctors (86.3%), mass media (20%) and friends or
      relatives (13.7%). It was found that the older age was associated with less
      knowledge (OR=0.93, CI: 0.88-0.97, p=0.004), and higher education with increased
      knowledge (OR=1.68, CI: 1.10-2.55, p=0.014) about osteoporosis. 56.4% of the
      participants were aware of at least one osteoporosis risk factor. In multivariate
      analysis, it was revealed that the participants who referred increased milk
      products consumption in childhood (OR=3.72, CI: 1.34-10.36, p=0.012) and current
      performance of physical activity (OR=13.06, CI: 3.22-53.05, p<0.001) were more
      likely to be informed about osteoporosis risk factors; age >61 years was
      associated with decreased knowledge of risk factors (OR=0.27, CI: 0.09-0.82,
      p=0.018). CONCLUSIONS: This study implies that a higher degree of participant's
      health education may result in the avoidance of osteoporosis risk factors.
      Increasing knowledge of osteoporosis should be a priority for future intervention
      programs in order to promote specific behavioural strategies for osteoporosis
      prevention.

PMID- 18079074
TI  - Pretreatment effects of moxibustion on the skin permeation of FITC-dextran.
AB  - This study was conducted to evaluate the pretreatment effects of different in
      vivo moxibustion on the permeation of a model high molecular compound, FITC
      dextran, with a mean molecular weight of 4 kDa (FD-4), through excised hairless
      rat skin. Direct or indirect moxibustion (0.10 g moxa) was pretreated
      consecutively 4 times every 5 min on the abdomen of hairless rats, and the
      permeation of FD-4 was determined through the excised skin over 8h from 30 min
      after starting the first moxibustion. This consecutive moxibustion pretreatment
      showed a significant increase in the skin temperature as well as skin permeation
      of FD-4 compared with the control group (no moxibustion pretreatment).
      Quantitative parameters showed an increase in skin temperature and skin
      permeation: the area under the skin temperature over control temperature-time
      curve during one burning cycle (5.0 min) (AUCtemp) or the maximum skin
      temperature during moxibustion (Tmax) and the cumulative amount of FD-4 permeated
      through skin over 8h (Q8) or steady-state flux were increased by moxibustion
      pretreatment. Then, the effect of pedestal thickness (distance from the moxa
      cylinder and skin surface), shape of the moxa cylinder (5mm diameter, 13 mm
      height or 9 mm diameter, 7 mm height), burning materials (moxa or aromatic
      incense), pedestal component (paper, potato or ginger) and moxibustion
      pretreatment method (direct or indirect moxibustion) was evaluated on the AUCtemp
      or Tmax and Q8 or flux. The amount of protein leached from the skin surface was
      also determined as an inflammatory index by this moxibustion pretreatment. When
      the skin temperature was increased to 60 degrees C, the Q8 or flux as well as the
      amount of protein leached were markedly increased. When the skin temperature was
      controlled to 42 to 45 degrees C by an adequate selection of pedestal thickness,
      shape of the moxa cylinder, burning materials, pedestal component and moxibustion
      pretreatment method, on the other hand, protein leaching remained unaltered, but
      the Q8 or flux significantly increased with the Tmax. This study thus provides
      credible evidence that moxibustion pretreatment increases the skin permeation of
      high molecular compounds.

PMID- 18079075
TI  - Synergistic enhancement of skin permeability by N-lauroylsarcosine and ethanol.
AB  - To develop formulations for transdermal drug delivery, this study tested the
      hypothesis that the anionic surfactant, N-lauroylsarcosine (NLS), and ethanol
      synergistically increase skin permeability by increasing the fluidity of stratum
      corneum lipid structure. Skin permeability experiments showed that transdermal
      delivery of fluorescein across human cadaver epidermis was increased by up to 47
      fold using formulations containing NLS in aqueous ethanol solutions. Skin
      permeability was increased by increasing NLS concentration in combination with 25
      50% ethanol solutions. Skin permeability was shown to correlate with skin
      electrical conductivity measurements, changes in differential scanning
      calorimetry lipid transition peak temperature, and Fourier transform infrared
      spectroscopy CH stretching peak shifts indicative of stratum corneum lipid
      fluidization and changes in protein conformation. Evidence for lipid extraction
      was also evident, but did not appear to be responsible for the observed increases
      in skin permeability. We conclude that NLS in aqueous ethanol formulations can
      dramatically increase skin permeability by a mechanism involving synergistic
      lipid-fluidization activity in the stratum corneum.

PMID- 18079076
TI  - Evaluation of in vivo efficacy of topical formulations containing soybean
      extract.
AB  - In the present study it was evaluated the: (i) functional stability of the
      soybean extract as a raw material and dispersed in two different topical
      formulations, (ii) skin retention using modified Franz diffusion cells, and (iii)
      in vivo activity of these formulations to inhibit 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced hydrogen peroxide (H(2)O(2)) and malondialdehyde (MDA)
      increases in the skin of hairless mice. The physico-chemical stability was
      evaluated by pH, globule size and centrifugation test. Furthermore, functional
      stability was also evaluated by antilipoperoxidative activity. The two topical
      formulations were stored at 4 degrees C, 30 degrees C/60% RH and 40 degrees C/70%
      RH for 6 months. The evaluation of the antiperoxidative stability of soybean
      extract itself and incorporated in formulations did not demonstrate loss of
      activity by storage at 4 degrees C/6 months. During 6 months of the study in
      different storage conditions the formulations 1 and 2 added or not with soybean
      extract were stable to physico-chemical tests. The effect of antioxidant
      compounds detected by the inhibition of MDA formation was time-dependent for
      formulation 2 as detected in the skin retention study. Pretreatment with
      formulation 1 or 2 significantly diminished TPA-induced H(2)O(2) and MDA
      generation. In conclusion, the present results suggest for the first time that
      formulations containing soybean extract may be a topical source of antioxidant
      compounds that decrease oxidative damages of the skin.

PMID- 18079077
TI  - Antipyretic, analgesic, and anti-inflammatory activities of the seaweed Sargassum
      fulvellum and Sargassum thunbergii in mice.
AB  - Dichloromethane, ethanol, and boiling water extracts of the brown seaweeds
      Sargassum fulvellum and Sargassum thunbergii were examined for antipyretic,
      analgesic, and anti-inflammatory activities in mice. The activities were
      evaluated against yeast-induced pyrexia, tail-flick test, and phorbol myristate
      acetate-induced inflammation (edema, erythema, and blood flow). The
      dichloromethane extract (0.4 mg/ear) of Sargassum fulvellum inhibited an
      inflammatory symptom of mouse ear edema by 79.1%. The ethanol extract (0.4
      mg/ear) of Sargassum thunbergii also inhibited edema by 72.1%. No acute toxicity
      was observed after p.o. administration of each extract (5 g/kg bw). These
      findings are consistent with various claims that these seaweeds can be used as
      remedies for inflammation-related symptoms.

PMID- 18079078
TI  - Pioneers in ethnopharmacology: the Dutch East India Company (VOC) at the Cape
      from 1650 to 1800.
AB  - The earliest inhabitants of South Africa are believed to be the Khoi-Khoi and San
      peoples, whose knowledge of economic botany is extensive. Their ethnomedical
      practice, based on the plant species indigenous to the region, is an oral
      tradition and particularly susceptible to disruption. The culture of both peoples
      has during the past 350 years come under increasing threat of extinction,
      resulting in the likely loss to science of important ethnomedical knowledge.
      While written records of Khoi-San traditional medical practice are preserved in
      English, they mainly cover the period from 1800 onward. Earlier written records
      do exist, but do not appear to have been adequately screened. The present study
      was undertaken in order to complete the historical written record by critically
      examining all potential sources of Khoi and San ethnomedical information, for the
      years 1650-1800. These sources comprised journals of exploratory expeditions,
      herbarium specimens, published academic works and archival records associated
      with the activities of the former Dutch East India Company (VOC) at the Cape. The
      results of the search show that the VOC had a great interest in Khoi and San
      traditional medicines and attempted to record this knowledge. The VOC archives in
      particular represent a largely untapped source of ethnomedical information with
      potential application in health care, new drug development and intellectual
      property protection.

PMID- 18079079
TI  - The influence of sex hormones on the elimination kinetics of ethanol.
AB  - The goal of the investigation was to research the influence of sex hormones on
      the elimination kinetics of ethanol. Forty-seven healthy men (average age 25+/
      6.1 years) and 61 healthy women (average age 24+/-2.4 years) received 0.79-0.95g
      of ethanol/kg body weight in the form of an alcohol beverage of their choice. The
      target concentration for both sexes was a blood alcohol concentration (BAC) of
      1.10g/kg. Blood samples for the determination of the ethanol concentration
      followed in the elimination phase in 10-20min intervals. The sex hormone levels
      (estradiol, progesterone and testosterone) were determined concomitantly from the
      serum. In men, the mean testosterone concentration was 5.3+/-1.6ng/ml, the mean
      estradiol concentration was 34.6+/-13.6pg/ml and the mean progesterone
      concentration was 0.9+/-0.3ng/ml. In women, the mean estradiol concentration was
      47.6+/-52.6pg/ml and the mean testosterone concentration was 0.8+/-0.4ng/ml.
      Progesterone displayed a so-called dummy effect in women. In the high
      progesterone group (n=11), the mean concentration was 11.1+/-3.5ng/ml and in the
      low progesterone group (n=50) the mean was 0.6+/-0.3ng/ml. The mean hourly
      elimination rate (beta60) was 0.1677+/-0.0311g/kg/h in men. In women, the mean
      hourly elimination rate was 0.2044+/-0.0414g/kg/h in the high progesterone group
      and 0.1850+/-0.0276g/kg/h in the low progesterone group (p<0.05). The beta60 for
      women in the low progesterone group was significantly higher than that of the
      men, whose progesterone levels fell within a similar range (p>0.01). These
      results allow one to conclude that the gender differences in the pharmacokinetics
      of ethanol can partly, but not completely, be explained by progesterone levels.

PMID- 18079080
TI  - Use of Lucilia species for forensic investigations in Southern Europe.
AB  - The aim of this study was to highlight the importance of evaluating entomological
      evidence in forensic investigations on a regional scale. To evaluate climatic,
      geographical and environmental influences on the selection of carrion-breeding
      fauna in Northern Italy and consequently on inferred forensic data (post-mortem
      intervals and post-mortem transfer), we present details of six indoor-outdoor
      cases. Results show that the most abundant species was Lucilia sericata, together
      with other fly species of entomo-forensic interest, belonging to the
      Calliphoridae and Sarcophagidae families. In particular, for the first time in
      Italy, we report finding Phormia regina, Lucilia ampullacea, Lucilia caesar and
      Sarcophaga (Pandelleana) protuberans on fresh cadavers. The active period of L.
      sericata in Northern Italy, according to previous findings in Southern Europe,
      revealing clearcut differences with phenologies in Northern Europe, has important
      consequences in estimating the period (season, months) of death in cases of long
      post-mortem intervals (several months or years) if empty puparia of this fly are
      found. According to our results, the distribution of L. sericata in areas with
      urban sprawl, like Northern Italian regions, cannot be used to evaluate post
      mortem transfer from an urban area to a rural one.

PMID- 18079081
TI  - [Mycobacterium ulcerans infection treated by Rifater, pyrazynamide, Myambutol,
      and surgery: a case report with a 6-year follow-up].
AB  - The author reports a case of pleuritis associated with a large homolateral Buruli
      thorax ulcer in a nine-year old female patient, in the Democratic Republic of
      Congo. Smears on Ziehl-Neelsen revealed acid-alcohol-resistant bacilli. The
      pathological histology confirmed a Mycobacterium ulcerans infection (Buruli
      ulcer). The treatment was surgical (excision-dressing-grafting) associated to
      antibiotic therapy (Rifater, Pyrazynamide, and Myambutol). After six years of
      follow up, no relapse was observed.

PMID- 18079082
TI  - [Spontaneous spleen rupture in the course of malaria].
AB  - The spontaneous rupture of malarial spleen is an uncommon complication. It
      usually occurs to a child and a recent expatriate. Its diagnosis is misleading
      into a context of infection. A 28-year-old European man, newly affected to Gabon,
      under chimioprophylactic drugs by chloroquine and proguanil, has been
      hospitalized in September 2000 because of an acute attack of malaria to
      Plasmodium falciparum. After four days treatment by quinine, he presented an
      abdominal pain with a Sub capsular Haematoma of the spleen confirmed by Scanner.
      The evolution was favourable under conservative treatment. The spontaneous
      rupture of malarial spleen is caused by Plasmodium vivax and falciparum. Twenty
      cases are reported in the literature. Conservative management permits to preserve
      the role of the spleen in immune response especially of the child and of people
      who regularly travel to endemic zone.

PMID- 18079083
TI  - Does ageing affect zinc homeostasis and dietary requirements?
AB  - Dietary intakes of zinc are lower in the elderly because of reduced energy
      requirements, and it is not clear whether ageing impacts on adaptive homeostatic
      mechanisms, namely absorptive efficiency and endogenous losses in the GI tract.
      Physiological requirements for zinc are unlikely to change significantly, but
      there are several attributes of ageing that may affect aspects of zinc metabolism
      (e.g. changes in gut structure and function, disease states, chronic
      inflammation, epigenetic changes in genes that express zinc-related proteins and
      drug regimens) that are worthy of further investigation. There is, as yet, no
      information on the effects of ageing on zinc transporters, and there are no
      sensitive and specific measures of zinc status, therefore dietary recommendations
      for zinc have been derived from factorial calculations using information on zinc
      absorption and loss, and estimates of dietary bioavailability.

PMID- 18079084
TI  - Have you had a tetanus booster in the last 10 years? Sensitivity and specificity
      of the question.
AB  - OBJECTIVE: To evaluate the accuracy of patients' recall of their last
      Tetanus/Diphtheria (Td) booster in the setting of employee health clinics known
      for high immunization rates and good documentation of vaccine status. METHODS:
      Five hundred and seventy-two patients of an employee health clinic answered a
      written questionnaire about whether they have had a Td booster in the last 10
      years. Answers were compared with patients' charts as the gold standard. RESULTS:
      The sensitivity of the question is 92.4% (95% CI 89.0-95.0) and specificity is
      26.5% (95% CI 12.9-44.4). Positive predictive value is 92.6% (95% CI 89.3-95.2)
      and negative predictive value is 25.7% (95% CI 12.5-43.3). Age and gender do not
      affect the accuracy of recall. CONCLUSION: A positive answer to this question is
      highly reliable whereas a negative answer is unreliable. PRACTICE IMPLICATIONS:
      In the setting of employee health clinics, when patients affirm the receipt of a
      Td booster within the previous 10 years, it is quite likely that they are up to
      date and do not require re-administration of the vaccine. Any other answer to
      this question (No, I do not know) is unreliable and a booster should be
      recommended if not contraindicated.

PMID- 18079085
TI  - Barriers and facilitators influencing the implementation of an interactive
      Internet-portal application for patient education in psychiatric hospitals.
AB  - OBJECTIVE: The purpose of this study was to identify barriers and facilitators
      influencing the implementation of an interactive Internet-portal application for
      patient education in psychiatric hospitals. METHODS: The data were collected from
      nurses by means of a questionnaire with thematic open-ended questions. The data
      was analysed using qualitative content analysis. RESULTS: Four main categories
      were formed to describe barriers and facilitators of portal implementation in
      psychiatric wards. These categories were organisational resources, nurses'
      individual characteristics, patient-related factors and portal-related factors.
      Some major barriers were identified restricting the use of the portal in patient
      education: lack of computers, lack of time for patients, nurses' negative
      attitudes towards computer use and lack of education. The main facilitators for
      portal use were appropriate technological resources, easy Internet access, enough
      time for portal use, and level of motivation among staff to use computers.
      CONCLUSION: The specific challenge in achieving patient education with the
      computer in psychiatric care is to ensure technological resources and that the
      staff are motivated to use computers. At the same time, attention should be paid
      the relationship between patient and nurse. PRACTICE IMPLICATIONS: It is
      important to examine the patient-nurse relationship in the education process and
      also to define the usability of the application from the patients' point of view.

PMID- 18079086
TI  - A study of lymph node ratio as a prognostic marker in colon cancer.
AB  - AIM: The aim of this study was to evaluate and describe the lymph node ratio
      (LNR) as a prognostic parameter for patients with colon cancer. As lymphatic
      involvement is the key, focus was set at stage III disease. Interest was directed
      at the possibility of identifying high-risk groups and the clinical
      implementation and consequence. METHOD: The study was retrospective using a
      database of clinical data of all cancer patients treated at our unit. It has been
      continuous in registration, inclusion and update since 1999 including survival
      and clinical features. All patients (n=265) diagnosed with stage III colon cancer
      during 1999-2003 were included for the study. LNR was calculated and quartile
      groups were created. LNR and associated parameters were analysed towards 3-year
      disease-free survival (DFS). Basic patient data as well as surgery, pathology and
      postoperative treatment were taken into consideration. RESULTS: Significant
      differences in disease-free survival were found for TNM N-status, tumour
      differentiation grade and LNR quartile group. There was a difference in 3-year
      DFS from 80% in LNR group 1 compared with less than 30% in group 4. These results
      were of prognostic interest both independently and in interaction with each
      other. High-risk groups could be identified and in the worst prognosis LNR group
      we also found a tendency towards more side effects with adjuvant chemotherapy.
      CONCLUSION: The lymph node ratio, the quota between the number of lymph node
      metastasis and assessed lymph nodes, is a highly significant (p<0.001) prognostic
      factor in stage III colon cancer. It can be an aid in identifying risk groups
      that could benefit from a more intense postoperative surveillance and possibly
      bring changes in adjuvant treatment strategy. More studies of clinical data,
      genetic and biochemical markers are needed in this patient group to understand
      the possible difference in tumour behaviour and tailor the treatment.

PMID- 18079087
TI  - [Oxygen arterial desaturation and upholding the oxygenation during intubation:
      question 2. Societe Francaise d'Anesthesie et de Reanimation].

PMID- 18079088
TI  - [Venous oximetry: physiology and therapeutic implications].
AB  - OBJECTIVES: The aims of this review are to point out the determinants of oxygen
      saturation of the haemoglobin of mixed venous blood (SvO(2)), to specify the
      correlations existing between SvO(2) and central venous saturation in superior
      vena cava (ScvO(2)), to determine and finally to locate the current place of
      venous oximetry in clinical practice. DATA SOURCES: A PubMed database research in
      English and French languages published until December 2006. The keywords were
      mixed venous blood oxygen saturation; oxygen consumption; oxygen delivery; oxygen
      extraction; tissue hypoxia; central venous oxygen saturation. DATA EXTRACTION:
      Data in selected articles were reviewed, clinical and basic science research
      relevant information was extracted. DATA SYNTHESIS: The SvO(2) reflects the
      peripheral extraction of oxygen (O(2)), O(2) delivery and consumption. Its value
      is related to four determinants: the O(2) consumption (VO(2)), cardiac flow (CF),
      haemoglobin level (Hb) and O(2) saturation of the haemoglobin of arterial blood
      (SaO(2)). ScvO(2) is more easily measurable than SvO(2). Under physiological
      conditions its value is 2 to 3% lower than that of SvO(2). In the critically ill
      patient, its value is 5% higher than that SvO(2). In most patients, changes in
      ScvO(2) values parallel those in SvO(2). The clinical interest of the monitoring
      of venous oximetry was underlined in cases of severe sepsis and septic shock, and
      during the perioperative period of major surgery. CONCLUSION: The management of
      patients in critical states with therapeutic goals integrating the monitoring of
      venous oximetry may reduce the morbidity and mortality of patients undergoing
      major surgery or hospitalised in the intensive care unit.

PMID- 18079089
TI  - Role of cell membrane receptors in the suppression of monocyte anti-microbial
      activity against Mycobacterium avium subsp. paratuberculosis.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP), the agent of paratuberculosis,
      is a slow growing mycobacteria that survives within ruminant mononuclear
      phagocytes by preventing cell activation and phagosome maturation. We
      investigated interactions between MAP and monocyte membrane receptors that result
      in activation of the mitogen-activated protein kinase (MAPK) p38 pathway and
      suppression of monocyte antimicrobial activity. Bovine monocytes were treated
      with blocking antibodies or specific chemical inhibitors of toll-like receptor 2
      (TLR2), CD14 and CR3 receptor before infection with MAP organisms. MAPKp38
      pathway activation, IL-10 expression and production, phagosome acidification, and
      MAP survival were determined. Our results indicated that MAP organisms-induced
      MAPKp38 activation occurs through partial interaction with TLR2. Blocking TLR2
      receptors decreased IL-10 mRNA expression but not IL-10 protein production,
      increased phagosome acidification, and increased the capacity of monocytes to
      kill MAP organisms. Furthermore, blocking CR3 receptors increased phagosome
      acidification but did not alter MAP killing. These finding suggest that phagosome
      acidification is dependent on a complex interaction between MAP and the phagosome
      wall that may involve multiple receptors but that organism killing is dependent
      on specific signaling involving TLR2 receptors.

PMID- 18079090
TI  - As2O3-induced oxidative stress and cycle progression in a human intestinal
      epithelial cell line (Caco-2).
AB  - Foods and drinking water are the main routes for human exposure to inorganic
      arsenic, the intestinal epithelium being the first barrier against such exogenous
      toxicants. The present study evaluates the effect of As(III) (0.5-25 microM) upon
      Caco-2 cells as an intestinal epithelia model. Cell viability, intracellular
      formation of reactive oxygen species (ROS), mitochondrial membrane potential
      (Deltapsim) changes, and cell cycle distribution in exposed cultures were
      evaluated. The intracellular production of ROS was seen to increase in a non-dose
      dependent manner at all concentrations tested, with impairment of cell
      mitochondrial enzyme function secondary to a loss of Deltapsim. Concentrations
      between 0.5 and 5 microM induce cell cycle transition from phase G1 to phase S,
      with no significant alteration in the proportion of cells in phase G2. These data
      suggest that As(III) could induce intestinal oxidative stress-cytotoxicity at
      mitochondrial functional level, and affect cell cycle progression. The data
      presented in this work may also suggest the impairment of essential survival
      processes in Caco-2 cells, induced after exposure to As(III) (1-25 microM).
      Oxidative stress and alteration of mitochondrial functionality could be early
      indicators of arsenic-induced cytotoxicity, with the resulting abnormal
      progression of the cell cycle.

PMID- 18079091
TI  - Testis-derived microRNA profiles of African clawed frogs (Xenopus) and their
      sterile hybrids.
AB  - Gene regulation was long predicted to play a vital role in speciation and species
      divergence. Only recently with the advent of new technologies, however, has it
      been possible to address the question of the relative contributions of different
      mechanisms of gene expression to the evolution of phenotypic diversity. Here we
      broaden the question and ask whether microRNAs, a large class of small regulatory
      RNAs, play a role in reproductive isolation between species by contributing to
      hybrid male sterility. MicroRNAs from the testes of clawed frogs (Xenopus) were
      extracted and the expression profiles of sterile hybrids were compared with males
      of a parental species. Hybrid testes were largely microRNA-depleted relative to
      those of nonhybrids, and this pattern was validated with quantitative RT-PCR. A
      number of candidate differential microRNAs from this study have previously been
      described as testis-specific in the mouse, suggesting that microRNA structural
      conservation may be associated with functional retention.

PMID- 18079092
TI  - [Real-time 3-dimensional echocardiography: can there be one more dimension?].
AB  - There is an essential importance of non-invasive imaging methods for evaluation
      of cardiac patients. Theoretically, the heart can be examined exactly, if due to
      its nature assessed in three dimensions (3D) concerning the heart cycle. In
      recent studies it has been confirmed that the second-generation real-time three
      dimensional echocardiography offers optimal opportunity for three-dimensional
      evaluation of cardiac structures. Real-time three-dimensional echocardiography is
      a valuable tool for exact evaluation of ventricular and atrial volumes and
      ventricular masses. Valves and congenital abnormalities can be analysed 'en-face'
      with this new methodology. The usefulness of this method with stress protocols
      has been confirmed. The aim of the present review is to demonstrate advantages of
      this new promising method showing recent technological limitations as well.

PMID- 18079093
TI  - [Fatty liver in childhood].
AB  - The abnormal lipid accumulation in the parenchymal cells of the liver is called
      fatty liver. In the background of this disease is the imbalance of fat
      accumulation and fat consumption: the overproduction of triglycerides is
      accumulated in the hepatocytes. Normally 5% of the cells contain triglycerides,
      but this value can increase to over 50% in fatty liver. It is called fatty
      infiltration under 50%, and fatty liver over 50%. This alteration does not cause
      cell function disturbance in mild forms, but it does in severe forms. In many
      cases it is the first sign of cell necrosis. Fatty liver must be taken seriously
      as it makes the liver sensitive to other toxic effects. It is not an independent
      disease, in many cases it is part of some other pathologic process. In the first
      phase (before the development of fibrosis) it is reversible, when the inducing
      cause disappears, the liver metabolizes the excessive triglycerides. In the
      treatment the basic process should be treated. So far no specific drug is known
      that would be able to decrease the fat accumulated in the hepatocytes.

PMID- 18079094
TI  - [Risk status of patients with peripheral arterial disease (PAD)].
AB  - The authors have analyzed clinical and laboratory risk factors of 168 patients
      with PAD and 82 control persons. Among the patients the prevalences of diabetes,
      coronary heart disease (CHD), and cerebrovascular disease (CVD) were 30.4%,
      39.9%, and 6.5%, respectively. 7.1% of the patients had CHD and CVD. Among
      patients with PAD and control persons, the prevalences of hypertension and
      current smoking were 76.2% vs 46.3% and 49.4% vs 28%. HDL-cholesterol and ApoA1
      levels were significantly lower, while the triglycerides, fibrinogen, hsCRP,
      homocysteine, creatinine, uric acid levels, and white blood cell count as well as
      plasma viscosity were significantly higher in the patient group compared with the
      values of control persons. Among the PAD patients the diabetics and the smokers
      had further unfavourable significant differencies in the laboratory findings
      compared with the data of non-diabetics and non-smokers. Correlations were
      detected between the hsCRP level and the white blood cell count, the plasma
      viscosity and the fibrinogen level, respectively. Examining 16 selected risk
      factors the average risk factor count of the patients was 7.79. 118 patients had
      lipid-lowering, and 142 patients had antithrombotic therapy. Our results
      emphasize the necessity of the secondary prevention among PAD patients.

PMID- 18079095
TI  - [Preliminary data of life and health insurance in the Roman Law (The collegium
      funeraticium and the collegium tenuiorum)].
AB  - With the explosion of insurance contracts in the last two hundred years both in
      Europe and around the rest of the world, there is a temptation to think that the
      financing and insuring on projects on limited or non-recourse terms is a
      relatively novel concept. This is, however, far from being true. Indeed, there is
      an early evidence of project financing techniques and insurance contracts being
      actively used during the ancient times. The first examples come from the Roman
      law but there are similar legal institutions even in the ancient Greek legal
      system. - The essay analyses the legal history of assurances on lives and health
      in the Roman law, especially the question of the collegium tenuiorum and the
      collegium funeraticium. In the centre of the studies are the analyses of their
      legal personality, the changes in the regulation concerning their foundation, the
      purpose and the internal organisation. The treatment of the main topics begins
      with fragments from the material of the Corpus Iuris Civilis by Justinian. After
      that the views of the most important authors and the contemporary investigations
      in the Roman law found the statements of the paper. As a result of these analyses
      we can see the process of development in the ancient legal systems, especially in
      the Roman law. And although these results have no immediate influence on the
      present legal regulation, it can demonstrate original tendencies in the field of
      insurances. This way we can prove that the Roman law is a still existing basis
      for the development in contractual law.

PMID- 18079096
TI  - [Childbirth and baby care portrayed on the Byzantine sacral artworks].

PMID- 18079097
TI  - [In memory of the first Hungarian textbook author, Samuel Racz, professor of
      physiology, on the bicentennial of his death].

PMID- 18079098
TI  - [Baron Henrik Kisteleki Levay, founder of the First Hungarian General Insurance
      Company].

PMID- 18079100
TI  - Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead.
AB  - Sprouting angiogenesis is an invasive process that involves proteolytic
      activities required for the degradation of the endothelial basement membrane,
      cell migration with removal of obstructing matrix proteins, and generation of
      space in the matrix to allow endothelial cells to form a proper lumen. In the
      last decade it has become clear that besides these matrix-degrading properties,
      proteases exert additional, more subtle functions that play a key role in
      angiogenesis. These functions are discussed with specific emphasis on membrane
      type-1 matrix metalloproteinase (MT1-MMP), other MMPs, and the related ADAMs (a
      disintegrin and metalloproteinase domain). Proteases modulate the balance between
      pro- and anti-angiogenic factors by activation and modification of growth factors
      and chemokines, ectodomain shedding with accompanied receptor activation,
      shedding of cytokines from membrane-bound precursors, and generation of (matrix)
      protein fragments that inhibit or activate angiogenesis. Furthermore, they
      participate in the recruitment of leukocytes and progenitor cells, which
      contribute to the onset and progression of angiogenesis. Proteases facilitate the
      mobilization of progenitor cells in the bone marrow as well as the entry of these
      cells and leukocytes into the angiogenic area. The interaction between pericytes
      and the newly formed endothelial tubes is accompanied by silencing of MMP
      activities. Better understanding of the various activities of proteases may be
      helpful in developing more specific inhibitors that could result in tailor-made
      modification of proteolytic activities in disease.

PMID- 18079101
TI  - Hypoxia-inducible factor 1 alpha: a new piece in the preconditioning puzzle.

PMID- 18079102
TI  - Cardiomyocyte cell cycle activation improves cardiac function after myocardial
      infarction.
AB  - AIMS: Cardiomyocyte loss is a major contributor to the decreased cardiac function
      observed in diseased hearts. Previous studies have shown that cardiomyocyte
      restricted cyclin D2 expression resulted in sustained cell cycle activity
      following myocardial injury in transgenic (MHC-cycD2) mice. Here, we investigated
      the effects of this cell cycle activation on cardiac function following
      myocardial infarction (MI). METHODS AND RESULTS: MI was induced in transgenic and
      non-transgenic mice by left coronary artery occlusion. At 7, 60, and 180 days
      after MI, left ventricular pressure-volume measurements were recorded and
      histological analysis was performed. MI had a similar adverse effect on cardiac
      function in transgenic and non-transgenic mice at 7 days post-injury. No
      improvement in cardiac function was observed in non-transgenic mice at 60 and 180
      days post-MI. In contrast, the transgenic animals exhibited a progressive and
      marked increase in cardiac function at subsequent time points. Improved cardiac
      function in the transgenic mice at 60 and 180 days post-MI correlated positively
      with the presence of newly formed myocardial tissue which was not apparent at 7
      days post-MI. Intracellular calcium transient imaging indicated that
      cardiomyocytes present in the newly formed myocardium participated in a
      functional syncytium with the remote myocardium. CONCLUSION: These findings
      indicate that cardiomyocyte cell cycle activation leads to improvement of cardiac
      function and morphology following MI and may represent an important clinical
      strategy to promote myocardial regeneration.

PMID- 18079103
TI  - Disruption of phospholipase Cgamma1 signalling attenuates cardiac tumor necrosis
      factor-alpha expression and improves myocardial function during endotoxemia.
AB  - AIMS: Lipopolysaccharide (LPS) induces tumor necrosis factor-alpha (TNF-alpha)
      expression in cardiomyocytes, which contributes to myocardial dysfunction during
      sepsis. The purpose of this study was to investigate the role of
      phosphatidylinositol (PI) phospholipase Cgamma1 (PLCgamma1) in cardiac TNF-alpha
      expression, and myocardial dysfunction during endotoxemia. METHODS AND RESULTS:
      In cultured mouse neonatal cardiomyocytes, LPS increased PLCgamma1
      phosphorylation. Knockdown of PLCgamma1 with specific siRNA or inhibition of
      PLCgamma1 with U73122 attenuated TNF-alpha expression induced by LPS. This action
      of PLCgamma1 was mediated through inositol-1,4,5-trisphosphate (IP3)/IP3 receptor
      (IP3R) pathways since blocking either IP3 or IP3R decreased LPS-induced TNF-alpha
      expression. In contrast, neither diacylglycerol agonist nor antagonist had any
      evident effect on LPS-induced TNF-alpha expression in cardiomyocytes. To
      investigate the role of PLCgamma1 in endotoxemia in vivo, wild-type and
      heterozygous PLCgamma1 knockout (PLCgamma1(+/-)) mice were pre-treated with
      either U73122, or its inactive analog U73343, or vehicle for 15 min, followed by
      LPS for 4 h. Inhibition of PLCgamma1 by U73122 or by heterozygous deletion of the
      PLCgamma1 gene decreased cardiac TNF-alpha expression. More importantly, LPS
      induced myocardial dysfunction was also attenuated in PLCgamma1(+/-) mice or by
      U73122 treatment. CONCLUSION: PLCgamma1 signalling induces cardiac TNF-alpha
      expression and myocardial dysfunction during LPS stimulation. The action of
      PLCgamma1 on TNF-alpha expression is mediated through IP3/IP3R pathways. The
      present results suggest that PLCgamma1 may be a potential therapeutic target for
      myocardial dysfunction in sepsis.

PMID- 18079104
TI  - Ca(2+) exchange with troponin C and cardiac muscle dynamics.
AB  - Controversy abounds in the cardiac muscle literature over the rate-limiting steps
      of cardiac muscle contraction and relaxation. However, the idea of a single
      biochemical mechanism being the all-inclusive rate-limiting step for cardiac
      muscle contraction and relaxation may be oversimplified. There is ample evidence
      that Ca(2+) concentration and dynamics, intrinsic cross-bridge properties, and
      even troponin C (TnC) Ca(2+) binding and dissociation can all modulate the
      mechanical events of cardiac muscle contraction and relaxation. However, TnC has
      generally been thought to play no role in influencing cardiac muscle dynamics due
      to the idea that Ca(2+) exchange with TnC is very rapid. This definitely is the
      case for isolated TnC, but not for the more sophisticated biochemical systems of
      reconstituted thin filaments and myofibrils. This review will discuss the
      biochemical influences on Ca(2+) exchange with TnC and their physiological
      implications.

PMID- 18079105
TI  - Cardiac function and modulation of sarcomeric function by length.
AB  - The Frank-Starling relationship provides beat-to-beat regulation of ventricular
      function by matching ventricular input and output. This review addresses the
      subcellular mechanisms by which the ventricle adjusts its output (i.e. stroke
      volume) by changes in end-diastolic volume. The subcellular processes are placed
      in the context of the four phases of the cardiac cycle with emphasis on the
      sarcomeric properties that mediate the number of force-generating cross-bridges
      recruited during pressure development. Additional mechanistic insight is provided
      regarding the factors that regulate myocyte loaded shortening speeds, which are
      paramount for dictating ejection volume. Emphasis is placed on the interplay
      between cross-bridge-induced cooperative activation of the thin filament and
      cooperative deactivation of the thin filament induced by muscle shortening. The
      balance of these two properties seems to determine systolic haemodynamics, and
      how this balance is modulated by sarcomere length, in part, underlies the Frank
      Starling relationship.

PMID- 18079106
TI  - Ageing-exaggerated proliferation of vascular smooth muscle cells is related to
      attenuation of Jagged1 expression in endothelial cells.
AB  - AIMS: Ageing has been shown to enhance neointima formation due to abnormal growth
      of vascular smooth muscular cells (VSMC), which is regulated by endothelial
      functions. The mechanism of how endothelium affects the growth of VSMC in the
      process remains unclear. We here examined the role of Jagged1, a regulator of
      cell growth. METHODS AND RESULTS: Male Sprague-Dawley rats at 3 (young) and 22
      (old) months of age were subjected to a balloon catheter injury in the thoracic
      aorta. After 4 weeks, the neointima formation in the injured artery of old rats
      was more than that of young rats. Compared with the young rats, the increase in
      Jagged1 expression in the endothelium of old rats after the injury was delayed,
      weakened, and shortened, suggesting an impaired response of Jagged1 to the
      injury. In contrast, the increase in the expression of proliferating cell nuclear
      antigen in the neointima was more significant and maintained longer in old rats
      than in the young ones. Moreover, the expression of Jagged1 in the cultured
      arterial endothelial cells (EC) of old animals was less than those of the young
      ones, which promoted the Platelet-derived growth factor (PDGF)-induced growth and
      migration of the co-cultured VSMC. Furthermore, suppression of Jagged1 expression
      by a small interfering RNA in the EC of young rats reduced alpha-smooth muscle
      actin and calponin expression and also intensified the PDGF-increased growth and
      migration of the co-cultured VSMC. CONCLUSION: Ageing enhanced VSMC
      proliferation, at least in part, through impairing Jagged1 expression in the EC
      after vascular injury.

PMID- 18079107
TI  - Rapamycin modulates the eNOS vs. shear stress relationship.
AB  - AIMS: Studies in animals and patients indicate that rapamycin affects
      vasodilatation differently in outer and inner curvatures of blood vessels. We
      evaluated in this study whether rapamycin affects endothelial nitric oxide
      synthase (eNOS) responsiveness to shear stress under normo- and
      hypercholesteraemic conditions to explain these findings. METHODS AND RESULTS:
      Shear stress levels were varied over a large range of values in carotid arteries
      of transgenic mice expressing human eNOS fused to enhanced green fluorescence
      protein. The mice were divided into control, low-dose rapamycin (3
      microg/kg/day), and high-dose rapamycin (3 mg/kg/day) groups and into
      normocholesteraemic and hypercholesteraemic (ApoE-/- on high cholesterol diet for
      3-4 weeks) groups. The effect of rapamycin treatment on eNOS was evaluated by
      quantification of eNOS expression and of intracellular protein levels by en face
      confocal microscopy. A sigmoid curve fit was used to described these data. The
      efficacy of treatment was confirmed by measurement of rapamycin serum levels (2.0
      +/- 0.5 ng/mL), and of p27kip1 expression in vascular tissue (increased by 2.4 +/
      0.5-fold). In control carotid arteries, eNOS expression increased by 1.8 +/- 0.3
      fold in response to rapamycin. In the treated vessels, rapamycin reduced maximal
      eNOS expression at high shear stress levels (>5 Pa) in a dose-dependent way and
      shifted the sigmoid curve to the right. Hypercholesteraemia had a tendency to
      increase the leftward shift and the reduction in maximal eNOS expression (P =
      0.07). CONCLUSION: Rapamycin is associated with high eNOS in low shear regions,
      i.e. in atherogenic regions, protecting these regions against atherosclerosis,
      and is associated with a reduction of eNOS at high shear stress affecting
      vasomotion in these regions.

PMID- 18079108
TI  - Association of NFKB1, which encodes a subunit of the transcription factor NF
      kappaB, with alcohol dependence.
AB  - A broad region on chromosome 4q has been linked to alcohol dependence
      (alcoholism). We hypothesized that such broad linkage regions represent the
      combined action of multiple genes. Seeking to identify genes within that region
      that are associated with alcoholism, we have tested the association of NFKB1,
      located at 4q24, with alcoholism. NFKB1 encodes a 105 kDa transcription inhibitor
      that is cleaved to the 50 kDa DNA-binding subunit of the ubiquitous transcription
      factor NF-kappaB. NF-kappaB regulates many genes relevant to brain function, and
      its actions can be potentiated by ethanol; thus, NFKB1 is an excellent candidate
      gene for alcoholism. Nineteen SNPs in and near NFKB1 were analyzed in a sample of
      219 multiplex alcoholic families of European American descent. Family-based
      association analyses detected significant evidence of association with eight SNPs
      and marginal evidence for five more. The association was driven by the affected
      individuals with earlier onset of alcoholism (55% of the sample with onset < or
      =21 years). Further analysis of the age of onset as a quantitative variable
      provided evidence for the association of 12 SNPs in this gene. Thus, variations
      in NFKB1 appear to affect the risk for alcoholism, particularly contributing to
      an earlier onset of the disease.

PMID- 18079110
TI  - Stepwise binding of tylosin and erythromycin to Escherichia coli ribosomes,
      characterized by kinetic and footprinting analysis.
AB  - Erythromycin and tylosin are 14- and 16-membered lactone ring macrolides,
      respectively. The current work shows by means of kinetic and chemical
      footprinting analysis that both antibiotics bind to Escherichia coli ribosomes in
      a two-step process. The first step established rapidly, involves a low-affinity
      binding site placed at the entrance of the exit tunnel in the large ribosomal
      subunit, where macrolides bind primarily through their hydrophobic portions.
      Subsequently, slow conformational changes mediated by the antibiotic hydrophilic
      portion push the drugs deeper into the tunnel, in a high-affinity site. Compared
      with erythromycin, tylosin shifts to the high-affinity site more rapidly, due to
      the interaction of the mycinose sugar of the drug with the loop of H35 in domain
      II of 23 S rRNA. Consistently, mutations of nucleosides U2609 and U754 implicated
      in the high-affinity site reduce the shift of tylosin to this site and
      destabilize, respectively, the final drug-ribosome complex. The weak interaction
      between tylosin and the ribosome is Mg2+ independent, unlike the tight binding.
      In contrast, both interactions between erythromycin and the ribosome are reduced
      by increasing concentrations of Mg2+ ions. Polyamines attenuate erythromycin
      affinity for the ribosome at both sequential steps of binding. In contrast,
      polyamines facilitate the initial binding of tylosin, but exert a detrimental,
      more pronounced, effect on the drug accommodation at its final position. Our
      results emphasize the role of the particular interactions that side chains of
      tylosin and erythromycin establish with 23 S rRNA, which govern the exact binding
      process of each drug and its response to the ionic environment.

PMID- 18079109
TI  - A novel connexin43-interacting protein, CIP75, which belongs to the UbL-UBA
      protein family, regulates the turnover of connexin43.
AB  - The degradation of connexin43 (Cx43) has been reported to involve both lysosomal
      and proteasomal degradation pathways; however, very little is known about the
      mechanisms regulating these Cx43 degradation pathways. Using yeast two-hybrid,
      glutathione S-transferase pull-down, and co-immunoprecipitation approaches, we
      have identified a novel Cx43-interacting protein of approximately 75 kDa, CIP75.
      Laser confocal microscopy showed that CIP75 is located primarily at the
      endoplasmic reticulum, as indicated by the calnexin marker, with Cx43 co
      localization in this perinuclear region. CIP75 belongs to the UbL (ubiquitin
      like)-UBA (ubiquitin-associated) domain-containing protein family with a N
      terminal UbL domain and a C-terminal UBA domain. The UBA domain of CIP75 is the
      main element mediating the interaction with Cx43, whereas the CIP75-interacting
      region in Cx43 resides in the PY motif and multiphosphorylation sites located
      between Lys 264 and Asn 302. Interestingly, the UbL domain interacts with the
      S2/RPN1 and S5a/RPN10 protein subunits of the regulatory 19 S proteasome cap
      subunit of the 26 S proteasome complex. Overexpression experiments suggested that
      CIP75 is involved in the turnover of Cx43 as measured by a significant
      stimulation of Cx43 degradation and reduction in its half-life with the opposite
      effects on Cx43 degradation observed in small interference RNA knockdown
      experiments.

PMID- 18079111
TI  - AMP-activated protein kinase subunit interactions: beta1:gamma1 association
      requires beta1 Thr-263 and Tyr-267.
AB  - AMP-activated protein kinase (AMPK) plays multiple roles in the body's overall
      metabolic balance and response to exercise, nutritional stress, hormonal
      stimulation, and the glucose-lowering drugs metformin and rosiglitazone. AMPK
      consists of a catalytic alpha subunit and two non-catalytic subunits, beta and
      gamma, each with multiple isoforms that form active 1:1:1 heterotrimers. Here we
      show that recombinant human AMPK alpha1beta1gamma1 expressed in insect cells is
      monomeric and displays specific activity and AMP responsiveness similar to rat
      liver AMPK. The previously determined crystal structure of the core of mammalian
      alphabetagamma complex shows that beta binds alpha and gamma. Here we show that a
      beta1(186-270)gamma1 complex can form in the absence of detectable alpha subunit.
      Moreover, using alanine mutagenesis we show that beta1 Thr-263 and Tyr-267 are
      required for betagamma association but not alphabeta association.

PMID- 18079112
TI  - Histone deacetylase inhibition modulates kynurenine pathway activation in yeast,
      microglia, and mice expressing a mutant huntingtin fragment.
AB  - The kynurenine pathway of tryptophan degradation is hypothesized to play an
      important role in Huntington disease, a neurodegenerative disorder caused by a
      polyglutamine expansion in the protein huntingtin. Neurotoxic metabolites of the
      kynurenine pathway, generated in microglia and macrophages, are present at
      increased levels in the brains of patients and mouse models during early stages
      of disease, but the mechanism by which kynurenine pathway up-regulation occurs in
      Huntington disease is unknown. Here we report that expression of a mutant
      huntingtin fragment was sufficient to induce transcription of the kynurenine
      pathway in yeast and that this induction was abrogated by impairing the activity
      of the histone deacetylase Rpd3. Moreover, numerous genetic suppressors of mutant
      huntingtin toxicity that are functionally unrelated converged unexpectedly on the
      kynurenine pathway, supporting a critical role for the kynurenine pathway in
      mediating mutant huntingtin toxicity in yeast. Histone deacetylase-dependent
      regulation of the kynurenine pathway was also observed in a mouse model of
      Huntington disease, in which treatment with a neuroprotective histone deacetylase
      inhibitor blocked activation of the kynurenine pathway in microglia expressing a
      mutant huntingtin fragment in vitro and in vivo. These findings suggest that a
      mutant huntingtin fragment can perturb transcriptional programs in microglia, and
      thus implicate these cells as potential modulators of neurodegeneration in
      Huntington disease that are worthy of further investigation.

PMID- 18079113
TI  - Identification of Francisella tularensis lipoproteins that stimulate the toll
      like receptor (TLR) 2/TLR1 heterodimer.
AB  - The innate immune response to Francisella tularensis is primarily mediated by
      TLR2, though the bacterial products that stimulate this receptor remain unknown.
      Here we report the identification of two Francisella lipoproteins, TUL4 and
      FTT1103, which activate TLR2. We demonstrate that TUL4 and FTT1103 stimulate
      chemokine production in human and mouse cells in a TLR2-dependent way. Using an
      assay that relies on chimeric TLR proteins, we show that TUL4 and FTT1103
      stimulate exclusively the TLR2/TLR1 heterodimer. Our results also show that yet
      unidentified Francisella proteins, possibly unlipi-dated, have the ability to
      stimulate the TLR2/TLR6 heterodimer. Through domain-exchange analysis, we
      determined that an extended region that comprises LRR 9-17 in the extra-cellular
      portion of TLR1 mediates response to Francisella lipoproteins and triacylated
      lipopeptide. Substitution of the corresponding LRR of TLR6 with the LRR derived
      from TLR1 enables TLR6 to recognize TUL4, FTT1103, and triacylated lipopeptide.
      This study identifies for the first time specific Fran-cisella products capable
      of stimulating a proinflammatory response and the cellular receptors they
      trigger.

PMID- 18079114
TI  - Neuroprotection by neurotrophic factors and membrane depolarization is regulated
      by calmodulin kinase IV.
AB  - Neurotrophic factors promote motoneuron (MN) survival through increased
      intracellular calcium (Ca(2+)) and regulation of the phosphatidylinositol (PI) 3
      kinase/protein kinase B (PKB) pathway by calmodulin (CaM). Activation of the PI 3
      kinase/PKB pathway is one of the well established mechanisms involved in MN
      survival. The Ca(2+)/CaM complex interacts with and modulates the functionality
      of a large number of proteins, including serine/threonine protein kinases such as
      Ca(2+)/CaM-dependent protein kinases (CaMKs). Using a primary culture of
      embryonic chicken spinal cord MNs, we investigated the role of CaMKIV in
      mediating this process. We cloned chicken CaMKIV and demonstrated its expression
      in purified MNs by means of reverse transcription-PCR, Western blot, and
      immunofluorescence. Using RNA interference, we show that endogenous CaMKIV
      mediates cell survival induced by neurotrophic factors or membrane
      depolarization. The survival effect is independent of CaMKIV kinase activity;
      however, CaMKIV functionality depends on the presence of Ca(2+)/CaM. Finally,
      CaMKIV associates to the p85 subunit of PI 3-kinase in a Ca(2+)-dependent manner,
      suggesting a role in regulating PI 3-kinase/PKB activation.

PMID- 18079115
TI  - Inhibition of AMP-activated protein kinase sensitizes cancer cells to cisplatin
      induced apoptosis via hyper-induction of p53.
AB  - Cisplatin is one of the most effective and widely used chemotherapeutic agents.
      However, one of the most salient limitations to the clinical application of
      cisplatin is the acquired or intrinsic drug resistance exhibited by some tumors.
      In the present study, we have assessed the potential of an intracellular energy
      balancing system as a target for augmentation of cisplatin sensitivity in tumors.
      AMP-activated protein kinase (AMPK) regulates the energy balance system by
      monitoring intracellular energy status. Here we demonstrate that AMPK is rapidly
      activated by cisplatin in AGS and HCT116 cancer cells. The inhibition of AMPK in
      those cells and in xenografts of HCT116 resulted in a remarkable increase in
      cisplatin-induced apoptosis, which was associated with hyper-induction of the
      tumor suppressor p53. We further showed that ERK, but not ATM (ataxia
      telangiectasia mutated) and ATR (ATM- and Rad3-related) kinases, was involved in
      the hyper-induction of p53 by the inhibition of cisplatin-induced AMPK. By way of
      contrast, cisplatin did not induce AMPK activation in HeLa cells, which appear to
      have a relatively high sensitivity to cisplatin-induced cytotoxicity, but
      expression of the constitutive active form of AMPK in HeLa cells resulted in a
      significant increase of cell viability after cisplatin treatment. Collectively,
      our data suggest that AMPK performs a pivotal function for protection against the
      cytotoxic effect of cisplatin, thereby implying that AMPK is one of the cellular
      factors determining the cellular sensitivity to cisplatin. On the basis of these
      observations, we propose that a strategy combining cisplatin and AMPK inhibition
      could be developed into a novel chemotherapeutic modality.

PMID- 18079116
TI  - Slo1 caveolin-binding motif, a mechanism of caveolin-1-Slo1 interaction
      regulating Slo1 surface expression.
AB  - The large conductance, voltage- and Ca2+-activated potassium (MaxiK, BK) channel
      and caveolin-1 play important roles in regulating vascular contractility. Here,
      we hypothesized that the MaxiK alpha-subunit (Slo1) and caveolin-1 may interact
      with each other. Slo1 and caveolin-1 physiological association in native vascular
      tissue is strongly supported by (i) detergent-free purification of caveolin-1
      rich domains demonstrating a pool of aortic Slo1 co-migrating with caveolin-1 to
      light density sucrose fractions, (ii) reverse co-immunoprecipitation, and (iii)
      double immunolabeling of freshly isolated myocytes revealing caveolin-1 and Slo1
      proximity at the plasmalemma. In HEK293T cells, Slo1-caveolin-1 association was
      unaffected by the smooth muscle MaxiK beta1-subunit. Sequence analysis revealed
      two potential caveolin-binding motifs along the Slo1 C terminus, one equivalent,
      1007YNMLCFGIY1015, and another mirror image, 537YTEYLSSAF545, to the consensus
      sequence, varphiXXXXvarphiXXvarphi. Deletion of 1007YNMLCFGIY1015 caused
      approximately 80% loss of Slo1-caveolin-1 association while preserving channel
      normal folding and overall Slo1 and caveolin-1 intracellular distribution
      patterns. 537YTEYLSSAF545 deletion had an insignificant dissociative effect.
      Interestingly, caveolin-1 coexpression reduced Slo1 surface and functional
      expression near 70% without affecting channel voltage sensitivity, and deletion
      of 1007YNMLCFGIY1015 motif obliterated channel surface expression. The results
      suggest 1007YNMLCFGIY1015 possible participation in Slo1 plasmalemmal targeting
      and demonstrate its role as a main mechanism for caveolin-1 association with Slo1
      potentially serving a dual role: (i) maintaining channels in intracellular
      compartments downsizing their surface expression and/or (ii) serving as anchor of
      plasma membrane resident channels to caveolin-1-rich membranes. Because the
      caveolin-1 scaffolding domain is juxtamembrane, it is tempting to suggest that
      Slo1-caveolin-1 interaction facilitates the tethering of the Slo1 C-terminal end
      to the membrane.

PMID- 18079117
TI  - Atrial natriuretic peptide-initiated cGMP pathways regulate vasodilator
      stimulated phosphoprotein phosphorylation and angiogenesis in vascular
      endothelium.
AB  - Nitric oxide (NO)- and atrial natriuretic peptide (ANP)-initiated cGMP signaling
      cascades are important in the maintenance of cardiovascular homeostasis. The
      molecular signaling mechanisms downstream of cGMP are not well understood,
      however. We have used small interfering RNA (siRNA) approaches to specifically
      knock down a series of signaling proteins in bovine aortic endothelial cells, and
      we have combined biochemical analyses with physiological assays to investigate
      cGMP-mediated signal transduction pathways. Activation of particulate guanylate
      cyclase (GC-A) by ANP leads to a substantial, dose-dependent, rapid, and
      sustained increase in intracellular cGMP. In contrast, stimulation of soluble
      guanylate cyclase by NO yields only a weak and transient increase in cGMP. ANP
      induced cGMP production is selectively suppressed by siRNA-mediated knockdown of
      GC-A. ANP greatly enhances the phosphorylation at Ser-239 of the vasodilator
      stimulated phosphoprotein (VASP), a major substrate of cGMP-dependent protein
      kinase (PKG) that significantly influences actin dynamics. Moreover, the ANP
      induced phosphorylation of VASP at Ser-239 is accompanied by increased actin
      stress fiber formation and enhanced endothelial tube formation. siRNA-mediated
      knockdown of GC-A, VASP, or PKG abolishes ANP-induced VASP Ser-239
      phosphorylation, stress fiber formation, and endothelial tube formation. We have
      demonstrated similar findings in human umbilical vein endothelial cells, where
      ANP substantially enhances intracellular cGMP content, phosphorylation of VASP at
      Ser-239, and endothelial tube formation. Taken together, our findings suggest
      that ANP-mediated cGMP signal transduction pathways regulate PKG phosphorylation
      of VASP Ser-239 in endothelial cells, resulting in reorganization of the actin
      cytoskeleton and enhancement of angiogenesis.

PMID- 18079118
TI  - LIM kinase-mediated cofilin phosphorylation during mitosis is required for
      precise spindle positioning.
AB  - The interaction of astral microtubules with cortical actin networks is essential
      for the correct orientation of the mitotic spindle; however, little is known
      about how the cortical actin organization is regulated during mitosis. LIM kinase
      1 (LIMK1) regulates actin dynamics by phosphorylating and inactivating cofilin,
      an actin-depolymerizing protein. LIMK1 activity increases during mitosis. Here we
      show that mitotic LIMK1 activation is critical for accurate spindle orientation
      in mammalian cells. Knockdown of LIMK1 suppressed a mitosis-specific increase in
      cofilin phosphorylation and caused unusual cofilin localization in the cell
      cortex in metaphase, instability of cortical actin organization and astral
      microtubules, irregular rotation and misorientation of the spindle, and a delay
      in anaphase onset. Similar results were obtained by treating the cells with a
      LIMK1 in hibitor peptide or latrunculin A or by overexpressing a non
      phosphorylatable cofilin(S3A) mutant. Furthermore, localization of LGN (a protein
      containing the repetitive Leu-Gly-Asn tripeptide motifs), an important regulator
      of spindle orientation, in the crescent-shaped cortical regions was perturbed in
      LIMK1 knockdown cells. Our results suggest that LIMK1-mediated cofilin
      phosphorylation is required for accurate spindle orientation by stabilizing
      cortical actin networks during mitosis.

PMID- 18079119
TI  - Green tea polyphenol epigallocatechin-3-gallate signaling pathway through 67-kDa
      laminin receptor.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), the principal polyphenol in green tea, has
      been shown to be a potent chemopreventive agent. Recently, 67-kDa laminin
      receptor (67LR) has been identified as a cell surface receptor for EGCG that
      mediates the anticancer activity of EGCG. Indeed, expression of 67LR confers EGCG
      responsiveness to tumor cells; however, the molecular basis for the anticancer
      activity of EGCG in vivo is not entirely understood. Here we show that (i) using
      a direct genetic screen, eukaryotic translation elongation factor 1A (eEF1A) is
      identified as a component responsible for the anticancer activity of EGCG; (ii)
      through both eEF1A and 67LR, EGCG induces the dephosphorylation of myosin
      phosphatase targeting subunit 1 (MYPT1) at Thr-696 and activates myosin
      phosphatase; and (iii) silencing of 67LR, eEF1A, or MYPT1 in tumor cells results
      in abrogation of EGCG-induced tumor growth inhibition in vivo. Additionally, we
      found that eEF1A is up-regulated by EGCG through 67LR. Overall, these findings
      implicate both eEF1A and MYPT1 in EGCG signaling for cancer prevention through
      67LR.

PMID- 18079120
TI  - Superoxide generation by chlorophyllide a reductase of Rhodobacter sphaeroides.
AB  - Chlorophyllide a reductase of Rhodobacter sphaeroides, which were reconstituted
      with the purified subunits of BchX, BchY, and BchZ, reduced ring B of
      chlorophyllide a using NADH under anaerobic conditions. Interestingly, suppressor
      mutations rescuing the inability of R. sphaeroides Fe-SOD mutant to grow in
      succinate-based minimal medium were predominantly mapped to BchZ subunit of
      chlorophyllide a reductase. The enzyme is labile in the presence of O(2).
      However, it generates superoxide at low O(2). The enzymes reconstituted with
      BchX, BchY, and the mutein subunit of BchZ from suppressor mutants showed less
      activity not only for chlorophyllide a reduction but also for superoxide
      generation compared with the enzyme reconstituted with the wild-type subunits.
      BchX, which contains FMN, and BchY are iron-sulfur proteins, whereas BchZ is a
      hemoprotein containing b-type heme. Neither chlorophyllide a reduction nor
      superoxide generation was observed with the enzyme reconstituted with the wild
      type subunits of BchX and BchY, and the apo-subunit of BchZ that had been
      refolded without heme, in which FMN of BchX was fully reduced. Thus, superoxide
      is generated not from FMN of BchX but from heme of BchZ. Consistently, the heme
      of BchZ muteins was half-reduced in its redox state compared with that of wild
      type BchZ.

PMID- 18079121
TI  - Human myosin Vc is a low duty ratio nonprocessive motor.
AB  - There are three distinct members of the myosin V family in vertebrates, and each
      isoform is involved in different membrane trafficking pathways. Both myosin Va
      and Vb have demonstrated that they are high duty ratio motors that are consistent
      with the processive nature of these motors. Here we report that the ATPase cycle
      mechanism of the single-headed construct of myosin Vc is quite different from
      those of other vertebrate myosin V isoforms. K(ATPase) of the actin-activated
      ATPase was 62 microm, which is much higher than that of myosin Va ( approximately
      1 mum). The rate of ADP release from actomyosin Vc was 12.7 s(-1), which was 2
      times greater than the entire ATPase cycle rate, 6.5 s(-1). P(i) burst size was
      0.31, indicating that the equilibrium of the ATP hydrolysis step is shifted to
      the prehydrolysis form. Our kinetic model, based on all kinetic data we
      determined in this study, suggests that myosin Vc spends the majority of the
      ATPase cycle time in the weak actin binding state in contrast to myosin Va and
      Vb. Consistently, the two-headed myosin Vc construct did not show processive
      movement in total internal reflection fluorescence microscope analysis,
      demonstrating that myosin Vc is a nonprocessive motor. Our findings suggest that
      myosin Vc fulfills its function as a cargo transporter by different mechanisms
      from other myosin V isoforms.

PMID- 18079122
TI  - Inorganic phosphate binds to the empty nucleotide binding pocket of conventional
      myosin II.
AB  - In muscle inorganic phosphate strongly decreases force generation in the presence
      of millimolar MgATP, whereas phosphate slows shortening velocity only at
      micromolar MgATP concentrations. It is still controversial whether reduction in
      shortening velocity by phosphate results from phosphate binding to the nucleotide
      free myosin head or from binding of phosphate to an actomyosin-ADP state as
      postulated for the inhibition of force generation by phosphate. Because most
      single-molecule studies are performed at micromolar concentrations of MgATP where
      phosphate effects on movement are rather prominent, clarification of the
      mechanisms of phosphate inhibition is essential for interpretation of data in
      which phosphate is used in single molecule studies to probe molecular events of
      force generation and movement. In in vitro assays we found that inhibition of
      filament gliding by inorganic phosphate was associated with increased
      fragmentation of actin filaments. In addition, phosphate did not extend dwell
      times of Cy3-EDA-ATP (2'(3')-O-[[2-[[6-[2-[3-(1-ethyl-1,3-dihydro-3,3-dimethyl-5
      sulfo-2H-indol-2-ylidene)-1-propenyl]-3,3-dimethyl-5-sulfo-3H-indolio]-1
      oxohexyl]amino]ethyl]carbamoyl]ATP) but reduced the number of Cy3-signals per
      field of view, approaching 50% at phosphate concentrations of 1-2 mM. Apparently,
      inhibition of movement does not result from binding of phosphate to an actomyosin
      ADP intermediate as proposed by Hooft and coworkers (Hooft, A. M., Maki, E. J.,
      Cox, K. K., and Baker, J. E. (2007) Biochemistry 46, 3513-3520) but, rather, from
      forming a strong-binding actomyosin-phosphate intermediate.

PMID- 18079123
TI  - Modest PGC-1alpha overexpression in muscle in vivo is sufficient to increase
      insulin sensitivity and palmitate oxidation in subsarcolemmal, not
      intermyofibrillar, mitochondria.
AB  - PGC-1alpha overexpression in skeletal muscle, in vivo, has yielded disappointing
      and unexpected effects, including disrupted cellular integrity and insulin
      resistance. These unanticipated results may stem from an excessive PGC-1alpha
      overexpression in transgenic animals. Therefore, we examined the effects of a
      modest PGC-1alpha overexpression in a single rat muscle, in vivo, on fuel
      handling proteins and insulin sensitivity. We also examined whether modest PGC
      1alpha overexpression selectively targeted subsarcolemmal (SS) mitochondrial
      proteins and fatty acid oxidation, because SS mitochondria are metabolically more
      plastic than intermyofibrillar (IMF) mitochondria. Among metabolically
      heterogeneous rat hindlimb muscles, PGC-1alpha was highly correlated with their
      oxidative fiber content and with substrate transport proteins (GLUT4, FABPpm, and
      FAT/CD36) and mitochondrial proteins (COXIV and mTFA) but not with insulin
      signaling proteins (phosphatidylinositol 3-kinase, IRS-1, and Akt2), nor with 5'
      AMP-activated protein kinase, alpha2 subunit, and HSL. Transfection of PGC-1alpha
      into the red (RTA) and white tibialis anterior (WTA) compartments of the tibialis
      anterior muscle increased PGC-1alpha protein by 23-25%. This also induced the up
      regulation of transport proteins (FAT/CD36, 35-195%; GLUT4, 20-32%) and 5'-AMP
      activated protein kinase, alpha2 subunit (37-48%), but not other proteins
      (FABPpm, IRS-1, phosphatidylinositol 3-kinase, Akt2, and HSL). SS and IMF
      mitochondrial proteins were also up-regulated, including COXIV (15-75%), FAT/CD36
      (17-30%), and mTFA (15-85%). PGC-1alpha overexpression also increased palmitate
      oxidation in SS (RTA, +116%; WTA, +40%) but not in IMF mitochondria, and
      increased insulin-stimulated phosphorylation of AKT2 (28-43%) and rates of
      glucose transport (RTA, +20%; WTA, +38%). Thus, in skeletal muscle in vivo, a
      modest PGC-1alpha overexpression up-regulated selected plasmalemmal and
      mitochondrial fuel-handling proteins, increased SS (not IMF) mitochondrial fatty
      acid oxidation, and improved insulin sensitivity.

PMID- 18079124
TI  - Peroxisome proliferator-activated receptor alpha deficiency abolishes the
      response of lipogenic gene expression to re-feeding: restoration of the normal
      response by activation of liver X receptor alpha.
AB  - The mRNA expression of lipogenic genes Scd-1 and Fas is regulated partly by the
      insulin-sensitive transcription factor SREBP-1c and liver X receptor alpha
      (LXRalpha). Compared with normal mice, the increase in the mRNA expression of
      hepatic Scd-1, Fas, and Srebp-1c was severely attenuated in peroxisome
      proliferator-activated receptor alpha (PPARalpha)-deficient mice during the
      transition from the starved to the re-fed states. The concentration of the
      membrane-bound form of SREBP-1c was also lower in the livers of the PPARalpha
      deficient mice during re-feeding but there was little difference in the
      concentration of the active, nuclear form, or in the abundance of Insig-2a mRNA.
      The response of plasma insulin to starvation and re-feeding was normal in the
      PPARalpha-deficient mice. Rat hepatocytes transfected with an adenovirus encoding
      a dominant negative form of PPARalpha were resistant to the stimulatory effects
      of insulin on Fas and Scd-1 mRNA expression in vitro. When LXRalpha was activated
      in vivo by inclusion of a non-steroidal ligand in the diet, the expression of the
      mRNA for hepatic Srebp-1c, Fas, and Scd-1 was increased severalfold in mice of
      both genotypes and resistance associated with PPARalpha deficiency was abolished
      during re-feeding. However, although re-feeding the LXRalpha ligand induced the
      immature form of SREBP-1c equally in the livers of both genotypes, the
      concentration of the nuclear form remained relatively low in the livers of the
      PPARalpha-deficient mice. We conclude that intact PPARalpha is required to
      mediate the response of Scd-1 and Fas gene expression to insulin and that this is
      normally achieved directly by activation of LXRalpha.

PMID- 18079125
TI  - Photoprotection in the antenna complexes of photosystem II: role of individual
      xanthophylls in chlorophyll triplet quenching.
AB  - In this work the photoprotective role of all xanthophylls in LHCII, Lhcb4, and
      Lhcb5 is investigated by laser-induced Triplet-minus-Singlet (TmS) spectroscopy.
      The comparison of native LHCII trimeric complexes with different carotenoid
      composition shows that the xanthophylls in sites V1 and N1 do not directly
      contribute to the chlorophyll triplet quenching. The largest part of the triplets
      is quenched by the lutein bound in site L1, which is located in close proximity
      to the chlorophylls responsible for the low energy state of the complex. The
      lutein in the L2 site is also active in triplet quenching, and it shows a longer
      triplet lifetime than the lutein in the L1 site. This lifetime difference depends
      on the occupancy of the N1 binding site, where neoxanthin acts as an oxygen
      barrier, limiting the access of O(2) to the inner domain of the Lhc complex,
      thereby strongly contributing to the photostability. The carotenoid triplet decay
      of monomeric Lhcb1, Lhcb4, and Lhcb5 is mono-exponential, with shorter lifetimes
      than observed for trimeric LHCII, suggesting that their inner domains are more
      accessible for O(2). As for trimeric LHCII, only the xanthophylls in sites L1 and
      L2 are active in triplet quenching. Although the chlorophyll to carotenoid
      triplet transfer is efficient (95%) in all complexes, it is not perfect, leaving
      5% of the chlorophyll triplets unquenched. This effect appears to be
      intrinsically related to the molecular organization of the Lhcb proteins.

PMID- 18079126
TI  - Sparse inverse covariance estimation with the graphical lasso.
AB  - We consider the problem of estimating sparse graphs by a lasso penalty applied to
      the inverse covariance matrix. Using a coordinate descent procedure for the
      lasso, we develop a simple algorithm--the graphical lasso--that is remarkably
      fast: It solves a 1000-node problem ( approximately 500,000 parameters) in at
      most a minute and is 30-4000 times faster than competing methods. It also
      provides a conceptual link between the exact problem and the approximation
      suggested by Meinshausen and Buhlmann (2006). We illustrate the method on some
      cell-signaling data from proteomics.

PMID- 18079127
TI  - A comparison of electronic records to paper records in mental health centers.
AB  - OBJECTIVE: Medication documentation is a critical aspect of quality patient care.
      The current study examined whether electronic medical records provide medication
      documentation that is more complete and faster to retrieve than traditional paper
      records. METHOD: This study involves a comparison of archived paper medical
      records to recent electronic medical records through chart review. A convenient
      sample of three large community mental health centers in Indiana was used.
      Medical charts for 180 patients with schizophrenia were rated on a checklist
      composed of 16 items that was adapted from a national project. Documentation that
      existed before implementation of the electronic medical record system was
      compared with that after implementation at each of the three centers. The main
      outcome measures were completeness and retrieval time of medication
      documentation. RESULTS: Electronic medical records provided medication
      documentation that was more complete and faster to retrieve than paper records
      across all centers and within each center. On average, electronic medical records
      were 40% more complete and 20% faster to retrieve. CONCLUSION: Electronic records
      have potential to improve medication management for patients in mental health
      centers over traditional records. However, medication documentation for patients
      diagnosed with schizophrenia was found to be deficient in many areas, regardless
      of documentation format.

PMID- 18079128
TI  - Potential synergy activity of the novel ceragenin, CSA-13, against clinical
      isolates of Pseudomonas aeruginosa, including multidrug-resistant P. aeruginosa.
AB  - OBJECTIVES: Previous data from our research had shown that the novel ceragenin,
      CSA-13, demonstrated concentration-dependent bactericidal activity against
      glycopeptide-resistant Staphylococcus aureus. However, it is unknown whether CSA
      13 demonstrates a similar property against Pseudomonas aeruginosa. We evaluated
      CSA-13 antipseudomonal activity compared with cefepime, meropenem,
      piperacillin/tazobactam, tobramycin and ciprofloxacin by susceptibility testing
      as well as in combination with cefepime, tobramycin and ciprofloxacin. METHODS:
      Fifty clinical isolates of P. aeruginosa were analysed by reference broth
      microdilution methods. Four strains with various susceptibilities were evaluated
      by time-killing curve (TKC) analysis at 0.5x, 1x, 2x and 4x MIC using an initial
      inoculum of 10(6) cfu/mL. For synergy testing, TKC analysis of CSA-13 alone and
      in combination with cefepime, tobramycin and ciprofloxacin at 0.5x MIC was
      performed. RESULTS: CSA-13 MIC50 and MBC50 were 16 and 16 mg/L, respectively. TKC
      analysis demonstrated concentration-dependent activity, with CSA-13 at 4x MIC
      achieving earliest kill at 1 h (99.9%, detection limit). Combination TKC analysis
      demonstrated synergy or additive effect with cefepime and ciprofloxacin, in some
      cases achieving early synergy. The addition of tobramycin to CSA-13 resulted in
      no difference in kill for two strains. CONCLUSIONS: CSA-13 showed concentration
      dependent activity against clinical isolates of P. aeruginosa, including
      multidrug-resistant P. aeruginosa. The addition of cefepime or ciprofloxacin to
      CSA-13 enhanced bacterial kill, achieving early synergy.

PMID- 18079129
TI  - Cortical folding patterns and predicting cytoarchitecture.
AB  - The human cerebral cortex is made up of a mosaic of structural areas, frequently
      referred to as Brodmann areas (BAs). Despite the widespread use of cortical
      folding patterns to perform ad hoc estimations of the locations of the BAs,
      little is understood regarding 1) how variable the position of a given BA is with
      respect to the folds, 2) whether the location of some BAs is more variable than
      others, and 3) whether the variability is related to the level of a BA in a
      putative cortical hierarchy. We use whole-brain histology of 10 postmortem human
      brains and surface-based analysis to test how well the folds predict the
      locations of the BAs. We show that higher order cortical areas exhibit more
      variability than primary and secondary areas and that the folds are much better
      predictors of the BAs than had been previously thought. These results further
      highlight the significance of cortical folding patterns and suggest a common
      mechanism for the development of the folds and the cytoarchitectonic fields.

PMID- 18079130
TI  - Risk of childhood leukemia associated with vaccination, infection, and medication
      use in childhood: the Cross-Canada Childhood Leukemia Study.
AB  - Current hypotheses consonant with the peak in leukemia incidence in early
      childhood point to an infectious etiology. The authors examined the effect of
      postnatal exposures predicted to affect early immune functioning, including
      childhood vaccinations, illness, medication use, and breastfeeding patterns.
      Children 0-15 years of age diagnosed with leukemia from 1990 to 1994 and resident
      within principal cities across Canada were eligible for inclusion. Through
      pediatric oncology centers and population-based cancer registries, 399 cases were
      ascertained at the time of diagnosis. For each participating case, an age-,
      gender-, and area-matched control was randomly selected from government health
      insurance rolls. Risk factor information was obtained through personal interviews
      with each child's parents or guardians. Conditional logistic regression was used
      to calculate odds ratios, with adjustment for potential confounders. Use of
      immunosuppressant medication by the index child led to a deficit of risk (odds
      ratio = 0.37, 95% confidence interval: 0.16, 0.84), while vitamin intake was
      positively associated with leukemia (odds ratio = 1.66, 95% confidence interval:
      1.18, 2.33). Breastfeeding for more than 6 months was also protective (p < 0.05).
      Results persisted for cases diagnosed with acute lymphoblastic leukemia and for
      children diagnosed at 1-5 years of age. These findings suggest a role for early
      immunologic challenge in the expression of childhood leukemia.

PMID- 18079131
TI  - Using head-on collisions to compare risk of driver death by frontal air bag
      generation: a matched-pair cohort study.
AB  - US air bag regulations were changed in 1997 to allow tests of unbelted male
      dummies in vehicles mounted and accelerated on sleds, resulting in longer crash
      pulses than rigid-barrier crashes. This change facilitated depowering of frontal
      air bags and was intended to reduce air bag-induced deaths. Controversy ensued as
      to whether sled-certified air bags could increase adult fatality risk. A matched
      pair cohort study of two-vehicle, head-on, fatal collisions between drivers
      involving first-generation versus sled-certified air bags during 1998-2005 was
      conducted by using Fatality Analysis Reporting System data. Sled certification
      was ascertained from public information and a survey of automakers. Conditional
      Poisson regression for matched-pair cohorts was used to estimate risk ratios
      adjusted for age, seat belt status, vehicle type, passenger car size, and model
      year for driver deaths in vehicles with sled-certified air bags versus first
      generation air bags. For all passenger-vehicle pairs, the adjusted risk ratio was
      0.87 (95% confidence interval: 0.77, 0.98). In head-on collisions involving only
      passenger cars, the adjusted risk ratio was 1.04 (95% confidence interval: 0.85,
      1.29). Increased fatality risk for drivers with sled-certified air bags was not
      observed. A borderline significant interaction between vehicle type and air bag
      generation suggested that sled-certified air bags may have reduced the risk of
      dying in head-on collisions among drivers of pickup trucks.

PMID- 18079132
TI  - Internet death notices as a novel source of mortality surveillance data.
AB  - Concerns about bioterrorism and influenza have focused attention on identifying
      novel data sources to enhance public health surveillance. The authors evaluated
      free Pittsburgh Post-Gazette Internet death notices for Allegheny County,
      Pennsylvania, as a potentially timely source of mortality data. Data abstracted
      from Internet death notices for 1998-2001 were compared with mortality records
      from the Pennsylvania Department of Health. Approximately 75% (44,294/60,281) of
      state records had death notices, and 91% (44,294/48,651) of death notices
      corresponded to a state record. There was a 2-day median lag from the date of
      death to online death notice publication. The date of death, gender, age, and
      name data were nearly 90% accurate and 60-100% complete. Increasing education and
      age were independently associated with increased Pittsburgh Post-Gazette
      reporting. Being non-White, female, or a nursing home resident were independently
      associated with decreased reporting. The Pittsburgh Post-Gazette Internet death
      notices provided accurate, timely mortality data for nearly three fourths of all
      Allegheny County deaths.

PMID- 18079133
TI  - Are brain volumes based on magnetic resonance imaging mediators of the
      associations of cumulative lead dose with cognitive function?
AB  - The authors used cross-sectional data (2001-2003) to consider the pathway through
      which past occupational lead exposure impacts cognitive function. They were
      motivated by studies linking cumulative lead dose with brain volumes, volumes
      with cognitive function, and lead dose with cognitive function. It was
      hypothesized that the brain regions associated with lead mediate a portion of the
      relation between lead dose and cognitive function. Data were derived from an
      ongoing US study of 513 former organolead manufacturing workers. Magnetic
      resonance imaging was used to perform a novel analysis to investigate mediation.
      Volumes associated with cognitive function and lead dose were derived by using
      registered images and were used in a subsequent mediation analysis. Cumulative
      lead dose was associated with adverse function in the visuo-construction,
      executive function, and eye-hand coordination domains. Regarding these domains,
      there was strong evidence of volumetric mediation of lead's effect on cognition
      in the visuo-construction domain and a moderate amount for executive function and
      eye-hand coordination. A second path-analysis-based approach was also used. To
      address the possibility that chance associations explained these findings, a
      permuted analysis was conducted, the results of which supported the mediation
      inferences. The approach to evaluating volumetric mediation may have general
      applicability in epidemiologic neuroimaging settings.

PMID- 18079134
TI  - Energy intake at breakfast and weight change: prospective study of 6,764 middle
      aged men and women.
AB  - To investigate the association between percentage of total daily energy intake
      consumed at breakfast and weight change in middle-aged men and women, the authors
      analyzed data from a prospective population-based cohort study from Norfolk,
      United Kingdom. Participants were 6,764 men and women aged 40-75 years at
      baseline (1993-1997). Participants completed a 7-day food diary at baseline, and
      objective measurements of height and weight were carried out at baseline and
      follow-up (1998-2000). Mean baseline body mass index (weight (kg)/height (m)(2))
      was lowest among persons in the highest quintile of percentage of daily energy
      consumed at breakfast (mean values were 26.0 in the highest quintile and 26.3 in
      the lowest quintile), despite higher daily total energy intake in this group.
      Although all participants gained weight, increased percentage of daily energy
      consumed at breakfast was associated with relatively lower weight gain (adjusted
      beta coefficient = -0.021, 95% confidence interval: -0.035, -0.007; p = 0.004).
      The association between percentage of daily energy intake consumed at breakfast
      and weight gain was independent of age, sex, smoking, total energy intake,
      macronutrient intake, social class, and physical activity. Redistribution of
      daily energy intake, so that more energy is consumed at breakfast and less energy
      is consumed later in the day, may help to reduce weight gain in middle-aged
      adults.

PMID- 18079135
TI  - The hypersensitive response; the centenary is upon us but how much do we know?
AB  - With the centenary of the first descriptions of 'hypersensitiveness' following
      pathogenic challenge upon us, it is appropriate to assess our current
      understanding of the hypersensitive response (HR) form of cell death. In recent
      decades our understanding of the initiation, associated signalling, and some
      important proteolytic events linked to the HR has dramatically increased. Genetic
      approaches are increasingly elucidating the function of the HR initiating
      resistance genes and there have been extensive analyses of death-associated
      signals, calcium, reactive oxygen species (ROS), nitric oxide, salicylic acid,
      and now sphingolipids. At the same time, attempts to draw parallels between
      mammalian apoptosis and the HR have been largely unsuccessful and it may be
      better to consider the HR to be a distinctive form of plant cell death. We will
      consider if the HR form of cell death may occur through metabolic dysfunction in
      which malfunctioning organelles may play a major role. This review will highlight
      that although our knowledge of parts of the HR is excellent, a comprehensive
      molecular model is still to be attained.

PMID- 18079136
TI  - Effect of age and sex on carotid intima-media thickness, elasticity and brachial
      endothelial function in healthy adults: the cardiovascular risk in Young Finns
      Study.
AB  - AIMS: The objective was to produce reference values and to analyse the
      associations of age and sex with carotid intima-media thickness (IMT), carotid
      compliance (CAC), and brachial flow-mediated dilatation (FMD) in young healthy
      adults. METHODS AND RESULTS: We measured IMT, CAC, and FMD with ultrasound in
      2265 subjects aged 24-39 years. The mean values (mean +/- SD) in men and women
      were 0.592 +/- 0.10 vs. 0.572 +/- 0.08 mm (P < 0.0001) for IMT, 2.00 +/- 0.66 vs.
      2.31 +/- 0.77%/10 mmHg (P < 0.0001) for CAC, and 6.95 +/- 4.00 vs. 8.83 +/- 4.56%
      (P < 0.0001) for FMD. The sex differences in IMT [95% confidence interval (CI)
      for sex difference -0.013 to 0.004 mm, P = 0.37] and CAC (-0.01 to 0.18%/10 mmHg,
      P = 0.09) became non-significant after adjustments with risk factors and carotid
      diameter. In FMD, the sex difference was unaltered after adjustments for risk
      factors, but was reversed after adjustment with brachial diameter (95% CI 0.18
      1.32%, P < 0.01). With aging, IMT increased 5.7 +/- 0.4 microm/year and CAC
      decreased 0.042 +/- 0.003%/10 mmHg/year. The association of age with IMT and CAC
      was slightly attenuated (12 and 22%, respectively) after adjustments with risk
      factors, but remained significant (both P < 0.0001). Aging was not significantly
      related to brachial FMD (P = 0.16). CONCLUSION: Reference values produced in the
      present study can be utilized in the cardiovascular risk stratification among
      young people. Sex differences in the markers of subclinical atherosclerosis were
      mostly explained by differences in risk factors and vessel size. This emphasizes
      the importance of risk factor control in the prevention of atherosclerosis in
      young adults.

PMID- 18079137
TI  - Surgical correction of ischaemic mitral regurgitation still a long way to go.
AB  - This editorial refers to Five-year echocardiographic results of combined
      undersized mitral ring annuloplasty and coronary artery bypass grafting for
      chronic ischaemic mitral regurgitation by S. Gelsomino et al., on page 231.

PMID- 18079138
TI  - Mild renal dysfunction associated with incident coronary artery disease in young
      males.
AB  - AIMS: Although impaired renal function is associated with adverse cardiovascular
      outcomes, it is unknown whether this association exists in young, healthy adults
      with normal or mildly impaired renal dysfunction. METHODS AND RESULTS We
      calculated the baseline creatinine clearance of young males without antecedent
      diabetes mellitus, coronary artery disease (CAD), or renal dysfunction, and
      examined their subsequent diagnosis of CAD, defined as coronary artery diameter
      stenosis of at least 50% and/or myocardial infarction. The 23 964 males, 32.5 +/-
      5.9 years old, had a baseline estimated creatinine clearance of 107.9 +/- 0.6 mL
      min(-1) per 1.73 m(2) (60-150 mL min(-1) per 1.73 m(2)). During a mean follow-up
      of 3.5 +/- 1.9 years, 77 subjects were diagnosed with CAD. After age adjustment,
      there was a progressive increase in the risk for CAD as the estimated creatinine
      clearance decreased [hazard ratio (HR) 4.77, 95% confidence interval 3.22-7.06, P
      < 0.001 for comparison between the fifth and first quintiles]. This association
      also persisted after further adjustments for conventional and ancillary risk
      factors for CAD (HR 2.10, 95% confidence interval 1.40-3.14, P < 0.001).
      Conclusion Reduced renal function in the normal to mildly impaired range is
      independently associated with increased risk for CAD among young, healthy males.

PMID- 18079139
TI  - Topology-Bayes versus Clade-Bayes in phylogenetic analysis.
AB  - Several features of currently used Bayesian methods in phylogenetic analysis are
      discussed. The distinction between Clade-Bayes and Topology-Bayes is presented
      and illustrated with an empirical example. Three problems with Bayesian
      phylogenetic methods--exaggerated clade support, inconsistently biased priors,
      and the impossibility of hypothesis testing of cladograms--are shown to be the
      result of using a Clade-based Bayesian approach. Topology-based Bayesian methods
      do not share these shortcomings.

PMID- 18079140
TI  - Synergistic neurotoxic effects of arsenic and dopamine in human dopaminergic
      neuroblastoma SH-SY5Y cells.
AB  - Parkinson's disease is an environmentally influenced, neurodegenerative disease
      of unknown origin that is characterized by the progressive loss of dopaminergic
      neurons in the substantia nigra pars compacta of the brain. Arsenic is an
      environmental contaminant found naturally in ground water, industrial waste, and
      fertilizers. The initial goal of the present study was to determine if a mixture
      of arsenite (As(+3)) and dopamine (DA) could cause enhanced degeneration of
      dopaminergic neuronal cells. Additional goals were to determine the mechanism
      (apoptosis or necrosis) of As- and DA-induced cell death and if death could be
      attenuated by antioxidants. The cell culture model employed was the SH-SY5Y
      neuroblastoma cell line that has been shown to possess differentiated
      characteristics of dopaminergic neurons. The results demonstrated that a mixture
      of As(+3) and DA was synergistic in producing the death of the SH-SY5Y cells when
      compared with exposure to either agent alone. A mixture of 10muM As(+3) and
      100muM DA produced almost a complete loss of cell viability over a 24-h period of
      exposure, whereas, each agent alone had minimal toxicity. It was shown that
      necrosis, and not apoptosis, was the mechanism of cell death produced by exposure
      of the SH-SY5Y cells to the mixture of As(+3) and DA. It was also demonstrated
      that the antioxidants, N-acetylcysteine, and Sulforaphane, attenuated the
      toxicity of the mixture of As(+3) and DA to the SH-SY5Y cells. This study
      provides initial evidence that As(+3) and DA synergistically can cause enhanced
      toxicity in cultured neuronal cells possessing dopaminergic differentiation.

PMID- 18079141
TI  - Sign language comprehension: the case of Spanish sign language.
AB  - This study aims to answer the question, how much of Spanish Sign Language
      interpreting deaf individuals really understand. Study sampling included 36 deaf
      people (deafness ranging from severe to profound; variety depending on the age at
      which they learned sign language) and 36 hearing people who had good knowledge of
      sign language (most were interpreters). Sign language comprehension was assessed
      using passages of secondary level. After being exposed to the passages, the
      participants had to tell what they had understood about them, answer a set of
      related questions, and offer a title for the passage. Sign language comprehension
      by deaf participants was quite acceptable but not as good as that by hearing
      signers who, unlike deaf participants, were not only late learners of sign
      language as a second language but had also learned it through formal training.

PMID- 18079142
TI  - Musculoskeletal symptoms among seafood production workers in North Norway.
AB  - AIMS: To investigate the prevalence of musculoskeletal complaints among male and
      female production workers in different types of seafood industries in North
      Norway and to analyse associations between musculoskeletal symptoms and some
      possible risk factors in the seafood industry. METHODS: A self-administered
      anonymous questionnaire, covering several aspects concerning occupational
      environment and health issues, was mailed to employees in seafood-processing
      plants in North Norway. RESULTS: A total of 1767 employees in 118 seafood
      processing plants participated giving a 50% response rate. This included 744
      production workers in whitefish, shrimp and salmon industries, and 129
      administrative workers in all types of seafood industries. The prevalence of
      musculoskeletal symptoms was high among seafood production workers. The odds
      ratio for symptoms from upper limbs was significantly higher for females compared
      to men. Production workers had the highest relative risk for symptoms from
      wrist/hands (OR = 4.1-9.4) and elbows (OR = 3.5-5.2) when compared to
      administrative workers. The main difference between types of seafood industries
      was the high prevalence of symptoms from wrist/hands among female (82%) and male
      (64%) production workers in the salmon industry compared to whitefish (62 and
      47%, respectively) and shrimp industry (66 and 37%, respectively). CONCLUSIONS:
      Musculoskeletal symptoms were found among the majority of production workers in
      the whitefish, shrimp and salmon industry, the highest prevalence being among
      female workers. The main difference between types of seafood industries was the
      high prevalence of symptoms from wrist/hands among workers in the salmon
      industry. Cold work was an important risk factor for musculoskeletal symptoms.

PMID- 18079143
TI  - Physical activity, weight gain and occupational health among call centre
      employees.
AB  - BACKGROUND: A need exists to address ergonomic, weight gain and obesity risks in
      sedentary occupations. AIM: To determine relationships between body mass index
      (BMI), weight gain, ergonomic and exercise variables in sedentary workers.
      METHODS: An anonymous questionnaire was administered regarding body weight,
      height, weight gained since employment, body part discomfort, shift fatigue, time
      to achieve job adaptation, physical activity, fitness centre membership, previous
      employment type and previous injury. RESULTS: Subjects were 393 volunteers (mean
      age 34 years, 71% female) employed in a call centre. Sixty-eight per cent of
      participants gained weight averaging 0.9 kg/month for 8 months. Significant
      findings (P < 0.05) were as follows: non-obese individuals gained less weight
      than obese individuals, fitness club members had higher BMIs and weight gains
      than non-members, previously injured individuals gained more weight than non
      injured individuals, non-weight gainers reported higher metabolic equivalent
      min/week expenditure in relation to vigorous exercise. CONCLUSIONS: Participants
      reported substantial weight gain over a period of 8 months. In contrast to
      walking and moderate exercise, only vigorous exercise was significantly
      associated with non-weight gain. Three risk factors were identified for weight
      gain: obese when hired, history of previous injury and lack of vigorous exercise.

PMID- 18079144
TI  - Variation in storage alpha-glucans of the Porphyridiales (Rhodophyta).
AB  - Storage glucans were analyzed in the Porphyridiales which include the most
      primitive and phylogenetically diverged species in the Rhodophyta, to understand
      early evolution of the glucan structure in the Rhodophyta. The storage glucans of
      both Galdieria sulphuraria and Cyanidium caldarium consisted of glycogen, while
      those of Rhodosorus marinus, Porphyridium purpureum, P. sordidum and Rhodella
      violacea could be defined as semi-amylopectin. X-ray diffraction analysis of the
      glucans demonstrated variation in the crystalline structure: the patterns in P.
      purpureum and R. violacea were of A- and B-types, respectively, while alpha
      glucans of R. marinus and P. sordidum displayed structures with lower
      crystallinity. Electron microscopic observations indicated that the alpha-glucans
      of P. sordidum consisted of two kinds of granules; a minor component of more
      dense granules with crystalline leaflets and a major component of softer ones
      without crystalline structure. Gel permeation chromatography showed that all the
      species containing the semi-amylopectin-type glucans also contained amylose,
      although the relative amounts of this fraction were different depending on the
      species. Our results are consistent with two distinct evolution scenarios defined
      either by the independent acquisition of semi-crystalline starch-like structures
      in the different plant lineages or more probably by the loss of starch and
      reversion to glycogen synthesis in cyanidian algae growing in hot and acid
      environments.

PMID- 18079145
TI  - Adherence to therapy in sub-Saharan non-dialysed Africans with chronic kidney
      diseases--a real burden.

PMID- 18079146
TI  - Kidney transplantation in the elderly--the Norwegian experience.
AB  - BACKGROUND: Elderly patients are the fastest growing population requiring renal
      replacement therapy. With increasing scarcity of organs, old patients are likely
      to remain in dialysis. We have had an active transplant program with elderly
      patients (i.e. > or = 70 years) and present results from our experiences.
      METHODS: From 1990 throughout 2005, we performed 301 first kidney
      transplantations in elderly patients. Data were compared with 513 senior patients
      aged 60-69 years and 512 control patients, aged 45-54 years, transplanted during
      the same time period. Time in dialysis prior to transplantation, number of
      patients receiving a living donor (LD) kidney, donor age, HLA mismatch,
      rejections, patient- and graft survival data were collected. RESULTS: The 5-year
      actuarial patient survival was 56% in elderly patients, 72% in senior patients; P
      < 0.001 versus elderly and 91% in control patients; P < 0.001 versus elderly.
      Death censored graft survival was similar in the different groups, 89% in
      elderly, 88% in senior and 90% in control patients. LD was used in 35%; 17% in
      elderly patients, 34% in senior patients; P < 0.001 and 47% in control patients;
      P < 0.001. Pre-emptive transplantation was performed in 19% of the patients; 10%
      in elderly patients, 18% in senior patients; P = 0.003 and 25% in control
      patients; P < 0.001. CONCLUSIONS: Our data show no difference in death censored
      graft survival between the age groups. Given the poor prognosis during dialysis
      treatment, selected elderly patients may successfully be offered a kidney
      transplant.

PMID- 18079147
TI  - Spontaneous remission of severe hyperparathyroidism with normalization of the
      reversed whole PTH/intact PTH ratio in a haemodialysis patient.

PMID- 18079148
TI  - T-cells in angiotensin-II-induced vascular damage.

PMID- 18079149
TI  - Kidney disease in cardiology.
AB  - Focusing on the convergence of cardiology and nephrology, this article marks the
      second year of NDT's section on Kidney Diseases beyond Nephrology. The clinical
      themes highlighted by the articles chosen for review include risk stratification
      and diagnosis of ischemic heart disease in severe chronic kidney disease and
      endstage renal disease patients, trials to reduce the risk of acute kidney injury
      (particularly contrast nephropathy) occurring with the invasive diagnosis and
      treatment of ischemic heart disease, and new data on the special clinical
      characteristics of dialysis patients with acute myocardial infarction. Finally,
      two clinical trials focusing on cardiovascular disease in severe kidney disease
      patients will be briefly highlighted.

PMID- 18079150
TI  - Membrano-proliferative glomerulonephritis associated with metastatic prostate
      carcinoma--should immunosuppressive therapy be considered?

PMID- 18079151
TI  - DNA polymerase kappa produces interrupted mutations and displays polar pausing
      within mononucleotide microsatellite sequences.
AB  - Microsatellites are ubiquitously present in eukaryotic genomes and are implicated
      as positive factors in evolution. At the nucleotide level, microsatellites
      undergo slippage events that alter allele length and base changes that interrupt
      the repetitive tract. We examined DNA polymerase errors within a [T](11)
      microsatellite using an in vitro assay that preferentially detects mutations
      other than unit changes. We observed that human DNA polymerase kappa (Pol kappa)
      inserts dGMP and dCMP within the [T](11) mononucleotide repeat, producing an
      interrupted 12-bp allele. Polymerase beta produced such interruptions at a lower
      frequency. These data demonstrate that DNA polymerases are capable of directly
      producing base interruptions within microsatellites. At the molecular level,
      expanded microsatellites have been implicated in DNA replication fork stalling.
      Using an in vitro primer extension assay, we observed sequence-specific synthesis
      termination by DNA polymerases within mononucleotides. Quantitatively, intense,
      polar pausing was observed for both pol kappa and polymerase alpha-primase within
      a [T](11) allele. A mechanism is proposed in which pausing results from DNA
      bending within the duplex stem of the nascent DNA. Our data support the concept
      of a microsatellite life-cycle, and are consistent with the models in which DNA
      sequence or secondary structures contributes to non-uniform rates of replication
      fork progression.

PMID- 18079152
TI  - Comprehensive viral oligonucleotide probe design using conserved protein regions.
AB  - Oligonucleotide microarrays have been applied to microbial surveillance and
      discovery where highly multiplexed assays are required to address a wide range of
      genetic targets. Although printing density continues to increase, the design of
      comprehensive microbial probe sets remains a daunting challenge, particularly in
      virology where rapid sequence evolution and database expansion confound static
      solutions. Here, we present a strategy for probe design based on protein
      sequences that is responsive to the unique problems posed in virus detection and
      discovery. The method uses the Protein Families database (Pfam) and motif finding
      algorithms to identify oligonucleotide probes in conserved amino acid regions and
      untranslated sequences. In silico testing using an experimentally derived
      thermodynamic model indicated near complete coverage of the viral sequence
      database.

PMID- 18079153
TI  - siRNA nanoformulation against the ret/PTC1 junction oncogene is efficient in an
      in vivo model of papillary thyroid carcinoma.
AB  - Delivery is a very important concern for therapeutic applications of siRNA. In
      this study, we have used chitosan-coated poly(isobutylcyanoacrylate)
      nanoparticles to deliver siRNA with a complementary sequence to the fusion
      oncogene ret/PTC1. By screening the mRNA junction we have selected a potent siRNA
      sequence able to inhibit this oncogene in a model of Papillary Thyroid Carcinoma
      cells. This siRNA sequence has then been validated by a shRNA approach using the
      same sequence. Furthermore, the high ret/PTC1 inhibition has triggered a
      phenotypic reversion of the transformed cells. We have designed well-defined
      chitosan decorated nanoparticles and succeeded to reduce their size. They have
      allowed to protect ret/PTC1 siRNA from in vivo degradation and leading to
      significant tumour growth inhibition after intratumoral administration.

PMID- 18079154
TI  - The burden of cancer at work: estimation as the first step to prevention.
AB  - OBJECTIVES: Work-related cancers are largely preventable. The overall aim of this
      project is to estimate the current burden of cancer in Great Britain attributable
      to occupational factors, and identify carcinogenic agents, industries and
      occupations for targeting risk prevention. METHODS: Attributable fractions and
      numbers were estimated for mortality and incidence for bladder, lung, non
      melanoma skin, and sinonasal cancers, leukaemia and mesothelioma for agents and
      occupations classified as International Agency for Research on Cancer (IARC)
      Group 1 and 2A carcinogens with "strong" or "suggestive" evidence for
      carcinogenicity at the specific cancer site in humans. Risk estimates were
      obtained from published literature and national data sources used for estimating
      proportions exposed. RESULTS: In 2004, 78,237 men and 71,666 women died from
      cancer in Great Britain. Of these, 7317 (4.9%) deaths (men: 6259 (8%); women:
      1058 (1.5%)) were estimated to be attributable to work-related carcinogens for
      the six cancers assessed. Incidence estimates were 13,338 (4.0%) registrations
      (men: 11,284 (6.7%); women 2054 (1.2%)). Asbestos contributed over half the
      occupational attributable deaths, followed by silica, diesel engine exhaust,
      radon, work as a painter, mineral oils in metal workers and in the printing
      industry, environmental tobacco smoke (non-smokers), work as a welder and
      dioxins. Occupational exposure to solar radiation, mineral oils and coal
      tars/pitches contributed 2557, 1867 and 550 skin cancer registrations,
      respectively. Industries/occupations with large numbers of deaths and/or
      registrations include construction, metal working, personal and household
      services, mining (not metals), land transport and services allied to transport,
      roofing, road repair/construction, printing, farming, the Armed Forces, some
      other service industry sectors and manufacture of transport equipment, fabricated
      metal products, machinery, non-ferrous metals and metal products, and chemicals.
      CONCLUSIONS: Estimates for all but leukaemia are greater than those currently
      used in UK health and safety strategy planning and contrast with small numbers
      (200-240 annually) from occupational accidents. Sources of uncertainty in the
      estimates arise principally from approximate data and methodological issues. On
      balance, the estimates are likely to be a conservative estimate of the true risk.
      Long latency means that past high exposures will continue to give substantial
      numbers in the near future. Although levels of many exposures have reduced,
      recent measurements of others, such as wood dust and respirable quartz, show
      continuing high levels.

PMID- 18079155
TI  - Subunit stoichiometry and channel pore structure of ion channels: all for one, or
      one for one?

PMID- 18079156
TI  - Target-cell-dependent plasticity within the mossy fibre-CA3 circuit reveals
      compartmentalized regulation of presynaptic function at divergent release sites.
AB  - Individual axons of central neurons innervate a large number of distinct
      postsynaptic targets belonging to divergent functional categories such as
      glutamatergic principal cells and inhibitory interneurons. While each bouton
      along a common axon should experience the same activity pattern in response to
      action potential firing within the parent presynaptic neuron, accumulating
      evidence suggests that neighbouring boutons contacting functionally distinct
      postsynaptic targets regulate their release properties independently, despite
      being separated by only a few microns. This target-cell-specific autonomy of
      presynaptic function can greatly expand the computational prowess of central
      axons to allow for precise coordination of large neuronal ensembles within a
      given circuit. An excellent example of target-cell-specific presynaptic
      mechanisms occurs in the CA3 hippocampus where mossy fibre (MF) axons of dentate
      gyrus granule cells target both principal cells and local circuit inhibitory
      interneurons via both anatomically and functionally specialized terminals. Of
      particular interest, mechanisms of both short- and long-term plasticity remain
      autonomous at these divergent release sites due to an anatomical and biochemical
      segregation of discrete molecular signalling cascades. Here we review roughly a
      decades worth of research on the MF-CA3 pathway to showcase the target-cell
      dependence of presynaptically expressed NMDA receptor-independent synaptic
      plasticity.

PMID- 18079157
TI  - LTP of GABAergic synapses in the ventral tegmental area and beyond.
AB  - One of the mechanisms by which the experience-dependent reorganization of neural
      circuitry can occur is through changes in synaptic strength. Almost every
      excitatory synapse in the mammalian brain exhibits LTP (long-term potentiation)
      or LTD (long-term depression), two cellular mechanisms of synaptic plasticity.
      However, LTP and LTD have been reported much more rarely at fast inhibitory
      GABA(A) receptor synapses. Our recent study suggests that in vivo morphine
      initiates a long-lasting alteration of GABAergic synapses in the ventral
      tegmental area (VTA) by blocking the mechanisms required for LTP of GABAergic
      synapses. Here we put this work into the context of other examples of synaptic
      plasticity at GABAergic synapses.

PMID- 18079158
TI  - The expression of GABAA beta subunit isoforms in synaptic and extrasynaptic
      receptor populations of mouse dentate gyrus granule cells.
AB  - The subunit composition of GABA(A) receptors influences their biophysical and
      pharmacological properties, dictates neuronal location and the interaction with
      associated proteins, and markedly influences the impact of intracellular
      biochemistry. The focus has been on alpha and gamma subunits, with little
      attention given to beta subunits. Dentate gyrus granule cells (DGGCs) express all
      three beta subunit isoforms and exhibit both synaptic and extrasynaptic receptors
      that mediate 'phasic' and 'tonic' transmission, respectively. To investigate the
      subcellular distribution of the beta subunits we have utilized the patch-clamp
      technique to compare the properties of 'tonic' and miniature inhibitory
      postsynaptic currents (mIPSCs) recorded from DGGCs of hippocampal slices of P20
      26 wild-type (WT), beta(2)(-/-), beta(2N265S) (etomidate-insensitive), alpha(1)(
      /-) and delta(-/-) mice. Deletion of either the beta(2) or the delta subunit
      produced a significant reduction of the tonic current and attenuated the increase
      of this current induced by the delta subunit-preferring agonist 4,5,6,7
      tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). By contrast, mIPSCs were not
      influenced by deletion of these genes. Enhancement of the tonic current by the
      beta(2/3) subunit-selective agent etomidate was significantly reduced for DGGCs
      derived from beta(2N265S) mice, whereas this manipulation had no effect on the
      prolongation of mIPSCs produced by this anaesthetic. Collectively, these
      observations, together with previous studies on alpha(4)(-/-) mice, identify a
      population of extrasynaptic alpha(4)beta(2)delta receptors, whereas synaptic
      GABA(A) receptors appear to primarily incorporate the beta(3) subunit. A
      component of the tonic current is diazepam sensitive and is mediated by
      extrasynaptic receptors incorporating alpha(5) and gamma(2) subunits. Deletion of
      the beta(2) subunit had no effect on the diazepam-induced current and therefore
      these extrasynaptic receptors do not contain this subunit. The unambiguous
      identification of these distinct pools of synaptic and extrasynaptic GABA(A)
      receptors should aid our understanding of how they act in harmony, to regulate
      hippocampal signalling in health and disease.

PMID- 18079159
TI  - Postnatal tuning of cutaneous inhibitory receptive fields in the rat.
AB  - Spinal nociceptive processing undergoes extensive maturation in the postnatal
      period. The large excitatory cutaneous receptive fields and sensitivity to
      mechanical stimulation in the first weeks of life suggest a lack of inhibitory
      control in developing spinal sensory pathways, which cannot be easily explained
      at the synaptic level. We hypothesized that developmental changes in dorsal horn
      inhibition occur at the network level, and tested this by mapping the spatial and
      modality organization of dorsal horn cell inhibitory receptive fields (RFs) in
      decerebrate spinal adult and neonatal rats. We report two novel results. First,
      although contralateral inhibition of dorsal horn cells was well established by
      postnatal day 3 (P3), inhibitory RFs were significantly less spatially restricted
      at P3 than in the adult and the intensity of inhibition across the RF was more
      evenly distributed in the neonate. Second, contralateral inhibitory RFs could be
      activated by both low- and high-intensity stimulation in the neonate, in contrast
      to the situation in adult where high-intensity pinch is normally required. These
      results demonstrate substantial postnatal changes in the organization or 'tuning'
      of inhibition in the developing dorsal horn, which are likely to contribute to
      the maturation of tactile and nociceptive spinal processing and coordinated
      sensorimotor and pain behaviour.

PMID- 18079160
TI  - Anticipatory changes in human motoneuron discharge patterns during motor
      preparation.
AB  - The influence of motor preparation on human motoneuron activity was studied by
      combining single motor unit recording techniques with reaction-time (RT) methods.
      The tonic activity of wrist extensor motor units associated with voluntary
      isometric contractions was analysed during preparation for a ballistic wrist
      extensor muscle contraction, using a time preparation procedure. Two durations of
      the preparatory period elapsing between the warning signal and the response
      signal were used in separate blocks of trials: a short preparatory period (1 s)
      allowing optimum time preparation, and a longer, non-optimum one (3 s). Changes
      in motoneuron tonic discharge patterns not associated with any changes in the
      force output were observed during the preparatory period, which suggests that
      these changes were subtle enough to prevent any changes in muscle contraction
      from occurring before the forthcoming movement. The changes observed were a
      lengthening of the mean interspike interval (ISI) and a decrease in the ISI
      variability. These data confirm that inhibitory mechanisms are activated during
      motor preparation and suggest that spinal inhibitory mechanisms are involved in
      the preparatory processes. The mechanisms possibly involved, such as presynaptic
      inhibition, disfacilitation processes or AHP conductance changes, are discussed.
      The fact that the preparation-induced effects on motoneuron activity were
      particularly prominent during the last part of the 3 s preparatory period
      suggests that they were probably related to the neural processes underlying
      temporal estimation. The anticipatory changes in motoneuron activity observed
      here during preparation for action provide evidence that central influences act
      on spinal motoneurons well before it is time to act.

PMID- 18079162
TI  - The medaka FoxP2, a homologue of human language gene FOXP2, has a diverged
      structure and function.
AB  - Forkhead box (Fox) genes are involved in organogenesis and cell differentiation.
      A mutation of FOXP2 was discovered in patients with severe defects in speech and
      language. The medaka FoxP2 was cloned in order to clarify the molecular evolution
      and difference in the protein structure and function by comparing human/mouse and
      medaka genes. The result showed that medaka FoxP2 had a 73.7% homology to the
      human and mouse counterparts, and its zinc finger, leucine zipper and forkhead
      domain structures were conserved. However, medaka FoxP2 lacked a long
      polyglutamine repeat and had two insertions of unique amino acid sequences. FoxP2
      expression was found in the epiphysis and retina, in addition to the midbrain and
      cerebellum. The transcriptional assay revealed that medaka FoxP2 showed a very
      weak repressive activity to the CC10 promoter while mouse Foxp2 exhibited a
      strong repressive activity. Mutational analyses of medaka FoxP2 showed that the
      three amino acids of forkhead domain were responsible for the weak repressive
      activity. These results suggest that medaka FoxP2 may play a different function
      in the development of the medaka fish.

PMID- 18079161
TI  - Mitochondrial ATP-sensitive K+ channels regulate NMDAR activity in the cortex of
      the anoxic western painted turtle.
AB  - Hypoxic mammalian neurons undergo excitotoxic cell death, whereas painted turtle
      neurons survive prolonged anoxia without apparent injury. Anoxic survival is
      possibly mediated by a decrease in N-methyl-d-aspartate receptor (NMDAR) activity
      and maintenance of cellular calcium concentrations ([Ca(2+)](c)) within a narrow
      range during anoxia. In mammalian ischaemic models, activation of mitochondrial
      ATP-sensitive K(+) (mK(ATP)) channels partially uncouples mitochondria resulting
      in a moderate increase in [Ca(2+)](c) and neuroprotection. The aim of this study
      was to determine the role of mK(ATP) channels in anoxic turtle NMDAR regulation
      and if mitochondrial uncoupling and [Ca(2+)](c) changes underlie this regulation.
      In isolated mitochondria, the K(ATP) channel activators diazoxide and
      levcromakalim increased mitochondrial respiration and decreased ATP production
      rates, indicating mitochondria were 'mildly' uncoupled by 10-20%. These changes
      were blocked by the mK(ATP) antagonist 5-hydroxydecanoic acid (5HD). During
      anoxia, [Ca(2+)](c) increased 9.3 +/- 0.3% and NMDAR currents decreased 48.9 +/-
      4.1%. These changes were abolished by K(ATP) channel blockade with 5HD or
      glibenclamide, Ca(2+)(c) chelation with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid (BAPTA) or by activation of the mitochondrial Ca(2+) uniporter
      with spermine. Similar to anoxia, diazoxide or levcromakalim increased
      [Ca(2+)](c) 8.9 +/- 0.7% and 3.8 +/- 0.3%, while decreasing normoxic whole-cell
      NMDAR currents by 41.1 +/- 6.7% and 55.4 +/- 10.2%, respectively. These changes
      were also blocked by 5HD or glibenclamide, BAPTA, or spermine. Blockade of
      mitochondrial Ca(2+)-uptake decreased normoxic NMDAR currents 47.0 +/- 3.1% and
      this change was blocked by BAPTA but not by 5HD. Taken together, these data
      suggest mK(ATP) channel activation in the anoxic turtle cortex uncouples
      mitochondria and reduces mitochondrial Ca(2+) uptake via the uniporter,
      subsequently increasing [Ca(2+)](c) and decreasing NMDAR activity.

PMID- 18079163
TI  - IRAK-4-dependent degradation of IRAK-1 is a negative feedback signal for TLR
      mediated NF-kappaB activation.
AB  - The activation of interleukin 1 receptor-associated kinase (IRAK)-1 is a key
      event in the transmission of signals from Toll-like receptors (TLRs). The
      catalytic activity of the protein kinase is not essential for its ability to
      activate nuclear factor (NF) kappaB, because transfection of a kinase-dead mutant
      of IRAK-1 (IRAK-1KD) is able to activate NF-kappaB in HEK293T cells. In the
      present study, we observed that the effect of IRAK-1KD was impaired by
      simultaneous expression of IRAK-4. The effect of IRAK-4 was accompanied by the
      phosphorylation and degradation of IRAK-1KD. Expression of IRAK-4KD instead of
      IRAK-4 did not cause these events. In IRAK-4-deficient Raw264.7 macrophages that
      were prepared by introducing short-hairpin RNA probes, the basal level of IRAK-1
      was increased markedly. Stimulation of these cells with TLR ligands did not cause
      the degradation of IRAK-1, which was clearly observed in the parent cells. These
      results suggested that the expression of IRAK-4 alone is sufficient to cause the
      degradation of IRAK-1; the autophosphorylation of IRAK-1 is not necessary to
      terminate the TLR-induced activation of NF-kappaB. IRAK-4 has an ability to
      induce the degradation of IRAK-1 in addition to its role as an activator of IRAK
      1.

PMID- 18079164
TI  - Impaired basal thermal homeostasis in rats lacking capsaicin-sensitive peripheral
      small sensory neurons.
AB  - We studied the effects of selective loss of capsaicin-sensitive primary sensory
      neurons on thermosensation and thermoregulation in rats. Neonatal capsaicin
      treatment in rats caused a remarkable decrease in the number of small-diameter
      neurons in the dorsal root ganglion (DRG) compared with their number in the
      control rats. Gene expression analysis for various thermo-sensitive transient
      receptor potential (TRP) channels indicated marked reductions in the mRNA levels
      of TRPV1 (70%), TRPM8 (46%) and TRPA1 (64%), but not of TRPV2, in the DRG of
      capsaicin-treated rats compared with those in the control rats. In addition to
      the heat and cold insensitivity, capsaicin-treated rats showed lower rectal core
      temperature, higher skin temperature and decreased sensitivity to ambient
      temperature alteration under normal housing at room temperature, suggesting
      impaired thermosensation and change in thermoregulation in the rats. Uncoupling
      protein 1 (UCP1) expression and the thermogenic ability in brown adipose tissues
      were attenuated in the capsaicin-treated rats. These results indicate a critical
      role of capsaicin-sensitive sensory neurons in both heat and cool sensation and
      hence in basal thermal homeostasis, which is balanced by heat release and
      production including UCP1 thermogenesis, following sensation of the ambient
      temperature.

PMID- 18079165
TI  - Expression of a novel 90-kDa protein, Lsd90, involved in the metabolism of very
      long-chain fatty acid-containing phospholipids in a mitosis-defective fission
      yeast mutant.
AB  - The fission yeast lsd1/fas2 strain carries a temperature-sensitive mutation of
      the fatty-acid-synthase alpha-subunit, exhibiting an aberrant mitosis lsd
      phenotype, with accumulation of very-long-chain fatty-acid-containing
      phospholipid (VLCFA-PL). A novel 90-kDa protein, Lsd90 (SPBC16E9.16c), was found
      to be newly expressed in small particle-like structures in lsd1/fas2 cells under
      restrictive conditions. Two mismatches leading to a double frame shift were found
      between the sequences of the lsd90(+) gene registered in the genomic database and
      the sequences determined experimentally at the amino acid, cDNA and genomic DNA
      levels. Unexpectedly, overexpression and disruption of the lsd90(+) gene in
      either lsd1/fas2 or wild-type cells did not affect either cell growth or
      expression of the lsd phenotype. The amounts of VLCFA-PL that accumulated in
      lsd90-overexpressing lsd1/fas2 cells were significantly lower than those in
      lsd1/fas2 cells, suggesting the involvement of Lsd90 in the metabolism of VLCFA
      PL.

PMID- 18079166
TI  - Axonal alpha-synuclein aggregates herald centripetal degeneration of cardiac
      sympathetic nerve in Parkinson's disease.
AB  - Degeneration of the cardiac sympathetic nerve occurs in both Parkinson's disease
      (PD) and dementia with Lewy bodies and begins early in the disease progression of
      PD, accounting for reduced cardiac uptake of meta-iodobenzylguanidine even in the
      early stages of Lewy body disease (LBD). We previously demonstrated that
      degeneration of the distal axons of the cardiac sympathetic nerve precedes loss
      of their mother neurons in the paravertebral sympathetic ganglia, suggesting
      distal dominant degeneration of the cardiac sympathetic nerve in PD. Because
      alpha-synuclein is one of the key molecules in the pathogenesis of this disease,
      we further investigated how alpha-synuclein aggregates are involved in this
      distal-dominant degeneration. Both cardiac tissues and paravertebral sympathetic
      ganglia were obtained for comparison from 20 patients with incidental Lewy body
      disease (ILBD), 10 with PD, 20 with multiple system atrophy (MSA) and 10 control
      subjects. Immunohistochemical analysis was performed using antibodies against
      tyrosine hydroxylase (TH) as a marker for sympathetic nerves, phosphorylated
      neurofilament as a marker for axons and phosphorylated alpha-synuclein for
      pathological deposits. We found that (i) alpha-synuclein aggregates in the
      epicardial nerve fascicles, namely the distal axons of the cardiac sympathetic
      nerve, were much more abundant in ILBD with preserved TH-ir axons than in this
      disease with decreased TH-ir axons and PD; (ii) alpha-synuclein aggregates in the
      epicardial nerve fascicles were closely related to the disappearance of TH-ir
      axons; (iii) in ILBD with preserved TH-ir axons, alpha-synuclein aggregates were
      consistently more abundant in the epicardial nerve fascicles than in the
      paravertebral sympathetic ganglia; (iv) this distal-dominant accumulation of
      alpha-synuclein aggregates was reversed in ILBD with decreased TH-ir axons and
      PD, which both showed fewer of these axons but more abundant alpha-synuclein
      aggregates in the paravertebral sympathetic ganglia and (v) MSA was completely
      different from ILBD and PD based on the preservation of TH-ir axons and the
      scarcity of alpha-synuclein aggregates in either the cardiac tissues or the
      paravertebral sympathetic ganglia. These findings indicate that accumulation of
      alpha-synuclein aggregates in the distal axons of the cardiac sympathetic nervous
      system precedes that of neuronal somata or neurites in the paravertebral
      sympathetic ganglia and that heralds centripetal degeneration of the cardiac
      sympathetic nerve in PD, which sharply contrasts with slight changes in MSA. This
      chronological and dynamic relationship between alpha-synuclein aggregates and
      distal-dominant degeneration of the cardiac sympathetic nervous system may
      represent the pathological mechanism underlying a common degenerative process in
      PD.

PMID- 18079167
TI  - Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with
      thin corpus callosum, cognitive decline and lower motor neuron degeneration.
AB  - Hereditary spastic paraplegias (HSP) are neurodegenerative diseases mainly
      characterized by lower limb spasticity associated, in complicated forms, with
      additional neurological signs. We have analysed a large series of index patients
      (n = 76) with this condition, either from families with an autosomal recessive
      inheritance (n = 43) or isolated patients (n = 33), for mutations in the recently
      identified SPG11 gene. We found 22 truncating mutations, including the first four
      splice-site mutations, segregating in seven isolated cases and 13 families.
      Nineteen mutations were novel. Two recurrent mutations were found in Portuguese
      and North-African patients indicating founder effects in these populations. The
      mutation frequency varied according to the phenotype, from 41%, in HSP patients
      presenting with a thin corpus callosum (TCC) visualized by MRI, to 4.5%, in
      patients with mental impairment without a TCC. Disease onset occurred during the
      first to the third decade mainly by problems with gait and/or mental retardation.
      After a mean disease duration of 14.9 +/- 6.6 years, the phenotype of 38 SPG11
      patients was severe with 53% of patients wheelchair bound or bedridden. In
      addition to mental retardation, 80% of the patients showed cognitive decline with
      executive dysfunction. Interestingly, the phenotype also frequently included
      lower motor neuron degeneration (81%) with wasting (53%). Slight ocular
      cerebellar signs were also noted in patients with long disease durations. In
      addition to a TCC (95%), brain MRI revealed white matter alterations (69%) and
      cortical atrophy (81%), which worsened with disease duration. In conclusion, our
      study reveals the high frequency of SPG11 mutations in patients with HSP, a TCC
      and cognitive impairment, including in isolated patients, and extends the
      associated phenotype.

PMID- 18079169
TI  - Measuring secondhand smoke exposure in children: an ecological measurement
      approach.
AB  - OBJECTIVE: Behavioral, environmental, and biological measures of secondhand smoke
      (SHS) exposure are reviewed with special consideration of medically at-risk
      children. METHODS: An ecological measurement framework is introduced to examine
      SHS exposure of children in the context of their physical and social
      environments. RESULTS: The proposed approach emphasizes the need to measure (a)
      who uses tobacco, (b) where and when exposure takes place, (c) what media are
      contaminated, (d) how exposure takes place, (e) how much a child was exposed, and
      (f) factors that contribute to why tobacco is used in a child's environment.
      CONCLUSIONS: Existing research suggests that medically at-risk children are among
      the most vulnerable populations for the harmful effects of SHS exposure. Yet,
      little is currently known about how SHS exposure affects these populations. The
      proposed approach provides a framework for the comprehensive assessment of SHS
      exposure to study its health effects and to design effective interventions.

PMID- 18079168
TI  - Sleep disturbances in school-age children with chronic pain.
AB  - OBJECTIVES: To examine associations between pain, functional outcomes, and sleep
      disturbances in children with chronic pain, specifically juvenile idiopathic
      arthritis (JIA), sickle cell disease (SCD), and headache (HA). Sleep disturbances
      were tested as a risk factor for increased functional disability and decreased
      health-related quality of life (HRQOL). METHODS: One hundred children (JIA n =
      30, SCD n = 26, HA n = 44; 8-12 years; 56% female) and their caregivers
      participated. Children completed questionnaires regarding pain, depression, and
      functional disability. Caregivers completed questionnaires regarding
      sociodemographics, child sleep habits, functional disability, and HRQOL. RESULTS:
      Levels of overall sleep disturbances were above the clinical cutoff for 53% of
      children with chronic pain. Sleep disturbances predicted lower physical HRQOL and
      higher functional disability, according to parent report. CONCLUSIONS: Sleep
      disturbances are common and associated with daytime functioning in school-age
      children with chronic pain, suggesting that assessment and treatment of sleep
      problems is clinically relevant.

PMID- 18079170
TI  - A new role for histone tail modifications in transcription elongation.

PMID- 18079171
TI  - Oncogene addiction: setting the stage for molecularly targeted cancer therapy.
AB  - In pugilistic parlance, the one-two punch is a devastating combination of blows,
      with the first punch setting the stage and the second delivering the knock-out.
      This analogy can be extended to molecularly targeted cancer therapies, with
      oncogene addiction serving to set the stage for tumor cell killing by a targeted
      therapeutic agent. While in vitro and in vivo examples abound documenting the
      existence of this phenomenon, the mechanistic underpinnings that govern oncogene
      addiction are just beginning to emerge. Our current inability to fully exploit
      this weakness of cancer cells stems from an incomplete understanding of oncogene
      addiction, which nonetheless represents one of the rare chinks in the formidable
      armor of cancer cells.

PMID- 18079172
TI  - A role for microRNAs in maintenance of mouse mammary epithelial progenitor cells.
AB  - microRNA (miRNA) expression profiles are often characteristic of specific cell
      types. The mouse mammary epithelial cell line, Comma-Dbeta, contains a population
      of self-renewing progenitor cells that can reconstitute the mammary gland. We
      purified this population and determined its miRNA signature. Several microRNAs,
      including miR-205 and miR-22, are highly expressed in mammary progenitor cells,
      while others, including let-7 and miR-93, are depleted. Let-7 sensors can be used
      to prospectively enrich self-renewing populations, and enforced let-7 expression
      induces loss of self-renewing cells from mixed cultures.

PMID- 18079173
TI  - Reinduction of ErbB2 in astrocytes promotes radial glial progenitor identity in
      adult cerebral cortex.
AB  - Radial glial cells play a critical role in the construction of mammalian brain by
      functioning as a source of new neurons and by providing a scaffold for radial
      migration of new neurons to their target locations. Radial glia transform into
      astrocytes at the end of embryonic development. Strategies to promote functional
      recovery in the injured adult brain depend on the generation of new neurons and
      the appropriate guidance of these neurons to where they are needed, two critical
      functions of radial glia. Thus, the competence to regain radial glial identity in
      the adult brain is of significance for the ability to promote functional repair
      via neurogenesis and targeted neuronal migration in the mature brain. Here we
      show that the in vivo induction of the tyrosine kinase receptor, ErbB2, in mature
      astrocytes enables a subset of them to regain radial glial identity in the mature
      cerebral cortex. These new radial glial progenitors are capable of giving rise to
      new neurons and can support neuronal migration. These studies indicate that ErbB2
      signaling critically modulates the functional state of radial glia, and induction
      of ErbB2 in distinct adult astrocytes can promote radial glial identity in the
      mature cerebral cortex.

PMID- 18079174
TI  - Long-range action of Nodal requires interaction with GDF1.
AB  - GDF1 (growth/differentiation factor 1), a Vg1-related member of the transforming
      growth factor-beta superfamily, is required for left-right patterning in the
      mouse, but the precise function of GDF1 has remained largely unknown. In contrast
      to previous observations, we now show that GDF1 itself is not an effective ligand
      but rather functions as a coligand for Nodal. GDF1 directly interacts with Nodal
      and thereby greatly increases its specific activity. Gdf1 expression in the node
      was found necessary and sufficient for initiation of asymmetric Nodal expression
      in the lateral plate of mouse embryos. Coexpression of GDF1 with Nodal in frog
      embryos increased the range of the Nodal signal. Introduction of Nodal alone into
      the lateral plate of Gdf1 knockout mouse embryos did not induce Lefty1 expression
      at the midline, whereas introduction of both Nodal and GDF1 did, showing that
      GDF1 is required for long-range Nodal signaling from the lateral plate to the
      midline. These results suggest that GDF1 regulates the activity and signaling
      range of Nodal through direct interaction.

PMID- 18079175
TI  - Protein kinase A and casein kinases mediate sequential phosphorylation events in
      the circadian negative feedback loop.
AB  - Regulation of circadian clock components by phosphorylation plays essential roles
      in clock functions and is conserved from fungi to mammals. In the Neurospora
      circadian negative feedback loop, FREQUENCY (FRQ) protein inhibits WHITE COLLAR
      (WC) complex activity by recruiting the casein kinases CKI and CKII to
      phosphorylate the WC proteins, resulting in the repression of frq transcription.
      On the other hand, CKI and CKII progressively phosphorylate FRQ to promote FRQ
      degradation, a process that is a major determinant of circadian period length.
      Here, by using whole-cell isotope labeling and quantitative mass spectrometry
      methods, we show that the WC-1 phosphorylation events critical for the negative
      feedback process occur sequentially-first by a priming kinase, then by the FRQ
      recruited casein kinases. We further show that the cyclic AMP-dependent protein
      kinase A (PKA) is essential for clock function and inhibits WC activity by
      serving as a priming kinase for the casein kinases. In addition, PKA also
      regulates FRQ phosphorylation, but unlike CKI and CKII, PKA stabilizes FRQ,
      similar to the stabilization of human PERIOD2 (hPER2) due to the phosphorylation
      at the familial advanced sleep phase syndrome (FASPS) site. Thus, PKA is a key
      clock component that regulates several critical processes in the circadian
      negative feedback loop.

PMID- 18079176
TI  - Intersubunit signaling in RecBCD enzyme, a complex protein machine regulated by
      Chi hot spots.
AB  - The Escherichia coli RecBCD helicase-nuclease, a paradigm of complex protein
      machines, initiates homologous genetic recombination and the repair of broken
      DNA. Starting at a duplex end, RecBCD unwinds DNA with its fast RecD helicase and
      slower RecB helicase on complementary strands. Upon encountering a Chi hot spot
      (5'-GCTGGTGG-3'), the enzyme produces a new 3' single-strand end and loads RecA
      protein onto it, but how Chi regulates RecBCD is unknown. We report a new class
      of mutant RecBCD enzymes that cut DNA at novel positions that depend on the DNA
      substrate length and that are strictly correlated with the RecB:RecD helicase
      rates. We conclude that in the mutant enzymes when RecD reaches the DNA end, it
      signals RecB's nuclease domain to cut the DNA. As predicted by this
      interpretation, the mutant enzymes cut closer to the entry point on DNA when
      unwinding is blocked by another RecBCD molecule traveling in the opposite
      direction. Furthermore, when RecD is slowed by a mutation altering its ATPase
      site such that RecB reaches the DNA end before RecD does, the length-dependent
      cuts are abolished. These observations lead us to hypothesize that, in wild-type
      RecBCD enzyme, Chi is recognized by RecC, which then signals RecD to stop, which
      in turn signals RecB to cut the DNA and load RecA. We discuss support for this
      "signal cascade" hypothesis and tests of it. Intersubunit signaling may regulate
      other complex protein machines.

PMID- 18079177
TI  - Retrosequence formation restructures the yeast genome.
AB  - Retrosequences generated by reverse transcription of mRNA transcripts have a
      substantial influence on gene expression patterns, generation of novel gene
      functions, and genome organization. The Ty1 retrotransposon is a major source of
      RT activity in the yeast, Saccharomyces cerevisiae, and Ty1 retromobility is
      greatly elevated in strains lacking telomerase. We report that Ty1-dependent
      formation of retrosequences derived from single-copy gene transcripts is
      progressively elevated as yeast cells senesce in the absence of telomerase.
      Retrosequences are frequently fused to Ty1 sequences, and occasionally to
      sequences from other mRNA transcripts, forming chimeric pseudogenes. Efficient
      retrosequence formation requires the homologous recombination gene RAD52.
      Selection for retrosequence formation is correlated with a high frequency of
      chromosome rearrangements in telomerase-negative yeast. Ty1-associated
      retrosequences were present at the breakpoint junctions of four chromosomes
      analyzed in detail. Our results support a role for reverse transcripts in
      promoting chromosome rearrangements.

PMID- 18079178
TI  - Kinetochore microtubule interaction during S phase in Saccharomyces cerevisiae.
AB  - In the budding yeast Saccharomyces cerevisiae, microtubule-organizing centers
      called spindle pole bodies (SPBs) are embedded in the nuclear envelope, which
      remains intact throughout the cell cycle (closed mitosis). Kinetochores are
      tethered to SPBs by microtubules during most of the cell cycle, including G1 and
      M phases; however, it has been a topic of debate whether microtubule interaction
      is constantly maintained or transiently disrupted during chromosome duplication.
      Here, we show that centromeres are detached from microtubules for 1-2 min and
      displaced away from a spindle pole in early S phase. These detachment and
      displacement events are caused by centromere DNA replication, which results in
      disassembly of kinetochores. Soon afterward, kinetochores are reassembled,
      leading to their recapture by microtubules. We also show how kinetochores are
      subsequently transported poleward by microtubules. Our study gives new insights
      into kinetochore-microtubule interaction and kinetochore duplication during S
      phase in a closed mitosis.

PMID- 18079179
TI  - Dormant origins licensed by excess Mcm2-7 are required for human cells to survive
      replicative stress.
AB  - In late mitosis and early G1, Mcm2-7 complexes are loaded onto DNA to license
      replication origins for use in the upcoming S phase. However, the amount of Mcm2
      7 loaded is in significant excess over the number of origins normally used. We
      show here that in human cells, excess chromatin-bound Mcm2-7 license dormant
      replication origins that do not fire during normal DNA replication, in part due
      to checkpoint activity. Dormant origins were activated within active replicon
      clusters if replication fork progression was inhibited, despite the activation of
      S-phase checkpoints. After lowering levels of chromatin-bound Mcm2-7 in human
      cells by RNA interference (RNAi), the use of dormant origins was suppressed in
      response to replicative stress. Although cells with lowered chromatin-bound Mcm2
      7 replicated at normal rates, when challenged with replication inhibitors they
      had dramatically reduced rates of DNA synthesis and reduced viability. These
      results suggest that the use of dormant origins licensed by excess Mcm2-7 is a
      new and physiologically important mechanism that cells utilize to maintain DNA
      replication rates under conditions of replicative stress. We propose that
      checkpoint kinase activity can preferentially suppress initiation within inactive
      replicon clusters, thereby directing new initiation events toward active clusters
      that are experiencing replication problems.

PMID- 18079180
TI  - Mismatch repair-dependent processing of methylation damage gives rise to
      persistent single-stranded gaps in newly replicated DNA.
AB  - O(6)-Methylguanine ((Me)G) is a highly cytotoxic DNA modification generated by
      S(N)1-type methylating agents. Despite numerous studies implicating DNA
      replication, mismatch repair (MMR), and homologous recombination (HR) in (Me)G
      toxicity, its mode of action has remained elusive. We studied the molecular
      transactions in the DNA of yeast and mammalian cells treated with N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG). Although replication fork progression was
      unaffected in the first cell cycle after treatment, electron microscopic analysis
      revealed an accumulation of (Me)G- and MMR-dependent single-stranded DNA (ssDNA)
      gaps in newly replicated DNA. Progression into the second cell cycle required HR,
      while the following G(2) arrest required the continued presence of (Me)G. Yeast
      cells overcame this block, while mammalian cells generally failed to recover, and
      those that did contained multiple sister chromatid exchanges. Notably, the arrest
      could be abolished by removal of (Me)G after the first S phase. These new data
      provide compelling support for the hypothesis that MMR attempts to correct
      (Me)G/C or (Me)G/T mispairs arising during replication. Due to the persistence of
      (Me)G in the exposed template strand, repair synthesis cannot take place, which
      leaves single-stranded gaps behind the replication fork. During the subsequent S
      phase, these gaps cause replication fork collapse and elicit recombination and
      cell cycle arrest.

PMID- 18079181
TI  - Mechanism of mRNA destabilization by the glmS ribozyme.
AB  - An array of highly structured domains that function as metabolite-responsive
      genetic switches has been found to reside within noncoding regions of certain
      bacterial mRNAs. In response to intracellular fluctuations of their target
      metabolite ligands, these RNA elements exert control over transcription
      termination or translation initiation. However, for a particular RNA class within
      the 5' untranslated region (UTR) of the glmS gene, binding of glucosamine-6
      phosphate stimulates autocatalytic site-specific cleavage near the 5' of the
      transcript in vitro, resulting in products with 2'-3' cyclic phosphate and 5'
      hydroxyl termini. The sequence corresponding to this unique natural ribozyme has
      been subjected to biochemical and structural scrutiny; however, the mechanism by
      which self-cleavage imparts control over gene expression has yet to be examined.
      We demonstrate herein that metabolite-induced self-cleavage specifically targets
      the downstream transcript for intracellular degradation. This degradation pathway
      relies on action of RNase J1, a widespread ribonuclease that has been proposed to
      be a functional homolog to the well-studied Escherichia coli RNase E protein.
      Whereas RNase E only poorly degrades RNA transcripts containing a 5' hydroxyl
      group, RNase J1 specifically degrades such transcripts in vivo. These findings
      elucidate key features of the mechanism for genetic control by a natural ribozyme
      and suggest that there may be fundamental biochemical differences in RNA
      degradation machinery between E. coli and other bacteria.

PMID- 18079182
TI  - PRMT6-mediated methylation of R2 in histone H3 antagonizes H3 K4 trimethylation.
AB  - The arginine methyltransferase PRMT6 (protein arginine methyltransferase 6) has
      been shown recently to regulate DNA repair and gene expression. As arginine
      methylation of histones is an important mechanism in transcriptional regulation,
      we asked whether PRMT6 possesses activity toward histones. We show here that
      PRMT6 methylates histone H3 at R2 and histones H4/H2A at R3 in vitro.
      Overexpression and knockdown analysis identify PRMT6 as the major H3 R2
      methyltransferase in vivo. We find that H3 R2 methylation inhibits H3 K4
      trimethylation and recruitment of WDR5, a subunit of the MLL (mixed lineage
      leukemia) K4 methyltransferase complex, to histone H3 in vitro. Upon PRMT6
      overexpression, transcription of Hox genes and Myc-dependent genes, both well
      known targets of H3 K4 trimethylation, decreases. This transcriptional repression
      coincides with enhanced occurrence of H3 R2 methylation and PRMT6 as well as
      reduced levels of H3 K4 trimethylation and MLL1/WDR5 recruitment at the HoxA2
      gene. Upon retinoic acid-induced transcriptional activation of HoxA2 in a cell
      model of neuronal differentiation, PRMT6 recruitment and H3 R2 methylation are
      diminished and H3 K4 trimethylation increases at the gene. Our findings identify
      PRMT6 as the mammalian methyltransferase for H3 R2 and establish the enzyme as a
      crucial negative regulator of H3 K4 trimethylation and transcriptional
      activation.

PMID- 18079183
TI  - The deacetylase HDAC6 is a novel critical component of stress granules involved
      in the stress response.
AB  - An essential part of the cellular response to environmental stress is a
      reversible translational suppression, taking place in dynamic cytoplasmic
      structures called stress granules (SGs). We discovered that HDAC6, a cytoplasmic
      deacetylase that acts on tubulin and HSP90 and also binds ubiquitinated proteins
      with high affinity, is a novel critical SG component. We found that HDAC6
      interacts with another SG protein, G3BP (Ras-GTPase-activating protein SH3 domain
      binding protein 1), and localizes to SGs under all stress conditions tested. We
      show that pharmacological inhibition or genetic ablation of HDAC6 abolishes SG
      formation. Intriguingly, we found that the ubiquitin-binding domain of HDAC6 is
      essential and that SGs are strongly positive for ubiquitin. Moreover, disruption
      of microtubule arrays or impairment of motor proteins also prevents formation of
      SGs. These findings identify HDAC6 as a central component of the stress response,
      and suggest that it coordinates the formation of SGs by mediating the motor
      protein-driven movement of individual SG components along microtubules.

PMID- 18079184
TI  - Apparent diffusion coefficient and cerebral blood volume in brain gliomas:
      relation to tumor cell density and tumor microvessel density based on
      stereotactic biopsies.
AB  - BACKGROUND AND PURPOSE: MR imaging-based apparent diffusion coefficient (ADC) and
      regional cerebral blood volume (rCBV) measurements have been related respectively
      to both cell and microvessel density in brain tumors. However, because of the
      high degree of heterogeneity in gliomas, a direct correlation between these MR
      imaging-based measurements and histopathologic features is required. The purpose
      of this study was to correlate regionally ADC and rCBV values with both cell and
      microvessel density in gliomas, by using coregistered MR imaging and stereotactic
      biopsies. MATERIALS AND METHODS: Eighteen patients (9 men, 9 women; age range, 19
      78 years) with gliomas underwent diffusion-weighted and dynamic susceptibility
      contrast-enhanced MR imaging before biopsy. Eighty-one biopsy samples were
      obtained and categorized as peritumoral, infiltrated tissue, or bulk tumor, with
      quantification of cell and microvessel density. ADC and rCBV values were measured
      at biopsy sites and were normalized to contralateral white matter on
      corresponding maps coregistered with a 3D MR imaging dataset. ADC and rCBV ratios
      were compared with quantitative histologic features by using the Spearman
      correlation test. RESULTS: The highest correlations were found within bulk tumor
      samples between rCBV and cell density (r=0.57, P < .001) and rCBV and microvessel
      density (r=0.46, P < .01). An inverse correlation was found between ADC and
      microvessel density within bulk tumor (r=-0.36, P < .05), whereas no significant
      correlation was found between ADC and cell density. CONCLUSION: rCBV regionally
      correlates with both cell and microvessel density within gliomas, whereas no
      regional correlation was found between ADC and cell density.

PMID- 18079185
TI  - Nontraumatic skull base defects with spontaneous CSF rhinorrhea and arachnoid
      herniation: imaging findings and correlation with endoscopic sinus surgery in 27
      patients.
AB  - BACKGROUND AND PURPOSE: Defects at the skull base leading to spontaneous CSF
      rhinorrhea are rare lesions. The purpose of our study was to correlate CT and MR
      findings regarding the location and content of CSF leaks in 27 patients with
      endoscopic sinus surgery observations. MATERIALS AND METHODS: Imaging studies in
      27 patients with intermittent CSF rhinorrhea (CT in every patient including 10
      examinations with intrathecal contrast, plain CT in 2 patients, and MR in 15
      patients) were analyzed and were retrospectively blinded to intraoperative
      findings. RESULTS: CT depicted a small endoscopy-confirmed osseous defect in 3
      different locations: 1) within the ethmoid in 15 instances (53.6% of defects)
      most commonly at the level of the anterior ethmoid artery (8/15); 2) adjacent to
      the inferolateral recess of the sphenoid sinus in 7 patients including one
      patient with bilateral lesions (8/28 defects, 28.6%); 3) within the midline
      sphenoid sinus in 5 of 28 instances (17.9%). Lateral sphenoid defects (3.5 +/-
      0.80 mm) were larger than those in ethmoid (2.7 +/- 0.77 mm, P < or = 0.029) or
      midsphenoid location (2.4 +/- 0.65 mm, P < or = 0.026). With endoscopy proven
      arachnoid herniation in 24 instances as reference, MR was correct in 14 of 15
      instances (93.3%), CT cisternography in 5 of 8 instances (62.5%). Plain CT in 1
      patient was negative. CONCLUSION: In patients with a history of spontaneous CSF
      rhinorrhea, CT was required to detect osseous defects at specific sites of
      predilection. MR enabled differentiating the contents of herniated tissue and
      allowed identification of arachnoid tissue as a previously hardly recognized
      imaging finding.

PMID- 18079186
TI  - Catheter angiography, MR angiography, and MR perfusion in posterior reversible
      encephalopathy syndrome.
AB  - BACKGROUND AND PURPOSE: The cause of posterior reversible encephalopathy syndrome
      (PRES) is unknown. Two primary hypotheses exist: 1) hypertension exceeding auto
      regulatory limits leading to forced hyper-perfusion and 2) vasoconstriction and
      hypo-perfusion leading to ischemia with resultant edema. The purpose of this
      study was to evaluate the catheter angiography (CA), MR angiography (MRA), and MR
      perfusion (MRP) features in PRES in order to render further insight into its
      mechanism of origin. MATERIALS AND METHODS: In 47 patients with PRES, 9 CAs and
      43 MRAs were evaluated for evidence of vasculopathy (vasoconstriction and
      vasodilation), and 15 MRP studies were evaluated for altered relative cerebral
      blood volume (rCBV) in PRES lesions and regions. Visualization of vessels on MRA
      and toxicity blood pressures were compared with the extent of hemispheric
      vasogenic edema. RESULTS: Vasculopathy was present in 8 of 9 patients on CA
      (direct correlation to MRA in 3/6 patients). At MRA, moderate to severe vessel
      irregularity consistent with vasoconstriction and vasodilation was present in 30
      of 43 patients and vessel pruning or irregularity in 7 patients, with follow-up
      MRA demonstrating reversal of vasoconstriction or vasodilation in 9 of 11
      patients. Vasogenic edema was less in patients with hypertension compared with
      patients who were normotensive. Preserved normal length of the posterior cerebral
      artery (PCA) was commonly seen in patients with severe hypertension despite
      diffuse or focal vasoconstriction or vasodilation. In these patients, lengthier
      visualization of the distal PCA correlated with a lower grade of hemispheric
      edema (P = .002). Cortical rCBV was significantly reduced in 51 of 59 PRES
      lesions and regions compared with a healthy reference cortex (average 61% of
      reference cortex) with mild decrease in the remainder. CONCLUSION: Vasculopathy
      was a common finding on CA and MRA in our patients with PRES, and MRP
      demonstrated reduced cortical rCBV in PRES lesions. Vasogenic edema was reduced
      in patients with hypertension, and superior distal PCA visualization correlated
      with reduced hemispheric edema in patients with PRES and severe hypertension.

PMID- 18079187
TI  - Intratumoral microhemorrhages on T2*-weighted gradient-echo imaging helps
      differentiate vestibular schwannoma from meningioma.
AB  - BACKGROUND AND PURPOSE: Vestibular schwannomas (VS) may be difficult to
      differentiate from cerebellopontine angle (CPA) meningiomas. Demonstration of
      microhemorrhages in VS on T2*-weighted gradient-echo (GRE) sequences may have
      potential value to differentiate VS from CPA meningiomas. MATERIALS AND METHODS:
      In this prospective study of 20 patients, MR imaging was performed with T2*
      weighted GRE in addition to all basic sequences. Histopathologic examination was
      performed after surgery. Intratumoral hemosiderin was confirmed by pigment
      staining. RESULTS: There were 15 patients in the VS group with 16 VS and 5 in the
      meningioma group with 5 posterior fossa meningiomas. Fourteen of the 16 VS and
      all 5 meningiomas were treated surgically and were confirmed on histopathologic
      examination. T2*-weighted GRE identified microhemorrhages on T2*-weighted
      sequence in 15 (93.75%) of the 16 VS. CT excluded calcification in all VS. T2
      weighted turbo spin-echo (TSE) and fluid-attenuated inversion recovery (FLAIR)
      images recognized microhemorrhages in 2 cases. Pigment staining confirmed
      hemosiderin in all 14 surgically treated VS, and none of the meningiomas showed
      microhemorrhages on MR imaging. For the detection of microhemorrhages, T2*
      weighted GRE showed a sensitivity of 93.8%, specificity of 100%, positive
      predictive value of 100%, and negative predictive value of 83.3%. The sensitivity
      of T2 TSE and FLAIR for microhemorrhage was 12.5%. The Fisher exact test showed a
      statistically significant difference in the differentiation of VS from meningioma
      on the basis of detection of microhemorrhages (P < .01). CONCLUSION: Most VS
      demonstrate microhemorrhages on T2*-weighted GRE. This finding is useful to
      differentiate VS from CPA meningiomas. T2*-weighted GRE should be used as a basic
      sequence to evaluate CPA tumors. Identification of microhemorrhages may have the
      potential to assess the aggressive biologic behavior of VS.

PMID- 18079188
TI  - CSF leaks: correlation of high-resolution CT and multiplanar reformations with
      intraoperative endoscopic findings.
AB  - BACKGROUND AND PURPOSE: Skull base defects can result in CSF leaks, with
      meningitis as a potential complication. Surgeons are now routinely repairing
      these leaks via a nasal endoscopic approach. Accurate preoperative imaging is
      essential for surgical planning. A variety of imaging regimens have been
      employed, including axial and direct coronal CT, CT cisternography with iodinated
      contrast, radionuclide cisternography, and MR imaging. Now that multidetector
      helical CT is available, the purpose of this study was to determine how well
      coronal and sagittal multiplanar reformatted (MPR) images generated from a high
      resolution axial dataset correlate with intraoperative findings in a group of
      patients with clinically proved CSF leaks. MATERIALS AND METHODS: We
      retrospectively reviewed imaging findings and surgical records of 19 patients who
      presented to our tertiary care institution during a 2.5-year period with
      clinically proved CSF leak. Patients underwent preoperative imaging with high
      resolution helical CT (section collimation, 10 patients with 0.625-mm and 9
      patients with 1.25-mm images), with MPR images processed by a neuroradiologist at
      a workstation. Two neuroradiologists, blinded to the intraoperative findings,
      determined the location and size of the skull base defects. All patients
      underwent endoscopic evaluation by an experienced sinonasal otolaryngologist, who
      confirmed the site of the CSF leak by direct inspection and measured the
      corresponding osseous defect. CT was considered accurate if it correctly
      localized the CSF leak and was within 2 mm of the endoscopic measurement.
      RESULTS: At endoscopy, 22 leaks of CSF were identified in 18 of 19 patients. CT
      correctly predicted the site of the leak in 20 (91%) of 22 cases and was accurate
      (within 2 mm of the endoscopic measurement) in 15 (75%) of 20 cases
      preoperatively localized. The CT measurement of the skull base defect differed
      from the endoscopic size in 5 (25%) of 20 cases, ranging from 7.4 mm below to 13
      mm above the intraoperative measurement. When analysis was limited to the
      subgroup of 10 patients who had 0.625-mm axial images, the accuracy was improved,
      and of the 11 CSF leaks described at CT, all were verified at endoscopy. In
      addition, the submillimeter CT accurately measured the size of the osseous defect
      in 9 (82%) of 11 cases. In the remaining 2 (18%) of 11 cases, CT minimally
      overestimated the size of the osseous defect by only 3 mm. CONCLUSION: Axial
      images, and coronal, sagittal, and oblique MPR images generated from high
      resolution axial CT performed well preoperatively, localizing the skull base
      defect responsible for the CSF leak. However, active manipulation of the axial
      dataset at a workstation is crucial in identifying and correctly describing these
      lesions. When submillimeter collimation is available, measurement of the osseous
      defects are accurate most of the time.

PMID- 18079189
TI  - Distal protection: maybe less than you think.

PMID- 18079190
TI  - Diffusion tensor pyramidal tractography in patients with anterior choroidal
      artery infarcts.
AB  - BACKGROUND AND PURPOSE: Anterior choroidal artery (AchoA) stroke often evolves
      into undulating hemipareses, which sometimes progress to high-grade hemiparesis
      or hemiplegia but may also completely regress. Spatial relationships of AchoA
      infarcts to corticospinal tracts (CSTs) and CST integrity were investigated with
      diffusion tensor imaging (DTI) to identify prognostic parameters related to
      diffusion anisotropy changes in AchoA stroke. MATERIALS AND METHODS: Twenty-five
      AchoA stroke patients were prospectively examined with 3T DTI and diffusion
      tensor tractography (DTT) within a 3-day mean interval after onset. Analysis
      included the following: 1) stroke size on diffusion-weighted imaging; 2)
      fractional anisotropy (FA) and apparent diffusion coefficients at the largest
      stroke extents versus contralateral homologous structures; 3) lesion location
      related to CST ("involvement"); 4) amount of fiber trajectories of affected
      versus nonaffected CST ("fiber ratio"); and 5) presence of ipsilateral fiber
      disruption. Imaging findings were related to clinical status 3 months after
      symptom onset with respect to favorable, moderate, or unfavorable motor outcome.
      RESULTS: FA differences (due to FA reduction in the affected versus nonaffected
      hemisphere) were significantly higher for patients with unfavorable outcome
      (P=.03). Patients with favorable outcome had nearly symmetrical FA. CSTs were
      involved in ischemic lesions in all but 2 patients (complete involvement, n=3;
      partial, n=20). Two CSTs were completely disrupted, and both patients were
      hemiplegic (no disruption, n=14; partial disruption, n=9). Fiber disruption and
      CST involvement correlated negatively with motor score after AchoA stroke (P <
      .01), whereas infarct size did not. CONCLUSION: DTT may explain resulting motor
      dysfunction in patients with AchoA infarcts with more notably decreased FA being
      an indicator for unfavorable outcome.

PMID- 18079191
TI  - The use of anti-tumour necrosis factor therapy in HIV-positive individuals with
      rheumatic disease.
AB  - OBJECTIVE: The purpose of this study was to examine the safety and efficacy of
      anti-tumour necrosis factor (TNF) agents (etanercept, infliximab and adalimumab)
      in HIV-positive patients with rheumatic diseases refractory to standard therapy.
      METHODS: Patients were treated with anti-TNF blocker with rheumatic diseases
      refractory to disease modifying antirheumatic drugs who had a CD4 count of >200
      mm3 and an HIV viral load of <60 000 copies/mm3 and no active concurrent
      infections. Changes in CD4 counts, HIV viral loads, or other adverse effects
      while on anti-TNF agents and clinical response were monitored for 28.1 (SD 20.9)
      months (range 2.5-55). RESULTS: Eight HIV-positive patients were treated with
      anti-TNF blockers (two patients with rheumatoid arthritis, three with psoriatic
      arthritis, one with undifferentiated spondyloarthritis, one with reactive
      arthritis and one with ankylosing spondylitis). No significant clinical adverse
      effect was attributed to this treatment in any patient. CD4 counts and HIV viral
      load levels remained stable in all patients. Three patients on etanercept therapy
      and two patients on infliximab had sustained clinical improvement in their
      rheumatic diseases. CONCLUSIONS: This retrospective series of eight patients
      suggests that treatment with anti-TNF-alpha therapy is a viable alternative in
      HIV patients without advanced disease with associated rheumatic diseases
      refractory to standard therapy.

PMID- 18079192
TI  - Non-gonadotropin-releasing hormone-mediated transcription and secretion of large
      human glycoprotein hormone alpha-subunit in human embryonic kidney-293 cells.
AB  - To identify genes that are most responsive to a sustained activation of a G(s)
      protein-coupled receptor, HEK293 cells were stably transfected with the beta(2)
      adrenergic receptor and stimulated with agonist isoproterenol (1 mum). A
      microarray study indicated that the gene with the highest stimulation index (500
      fold) encoded the common alpha-subunit of human glycoprotein hormones (GPHalpha).
      Induction of GPHalpha transcription in response to cAMP elevations resulted in a
      dramatic increase (600-fold) of protein secretion as shown by RT-PCR and a highly
      specific time-resolved immunofluorometric assay. Cloning and sequencing of the
      GPHalpha cDNA and mass spectrometric analysis of HPLC-purified GPHalpha derived
      from serum-free HEK293-beta(2)-adrenergic receptor-stimulated cells verified the
      nature of the molecule. Enzymatic deglycosylation with subsequent Western blots
      revealed that this was a large hyperglycosylated form of GPHalpha that had not
      been associated with a beta-subunit previously. This uncombined variant is known
      to be either cosecreted with GPHs from the pituitary, the placenta, and a variety
      of tumors or secreted without GPHs from APUD cells and rare tumors. Moreover, it
      is similar to GPHalpha found at high concentrations in seminal plasma. As shown
      by a panel of endogenous or transfected G protein-coupled receptors in HEK293
      cells, the expression of large GPHalpha was controlled by G(s)- and G(q)- but not
      G(i)-dependent receptors and mediated via cAMP and Ca(++) release. This suggests
      that Gq- or G(s)-coupled receptors other than the classical GnRH receptor may
      play a role in the regulation of nonpituitary, nonplacental GPHalpha secretion
      under physiological and pathological conditions.

PMID- 18079193
TI  - Forkhead box protein O1 negatively regulates skeletal myocyte differentiation
      through degradation of mammalian target of rapamycin pathway components.
AB  - The forkhead transcription factor forkhead box protein O1 (FoxO1), a downstream
      target of phosphatidylinositol 3-kinase/Akt signaling, has been reported to
      suppress skeletal myocyte differentiation, but the mechanism by which FoxO1
      regulates myogenesis is not fully understood. We have previously demonstrated
      that a nutrient-sensing mammalian target of rapamycin (mTOR) pathway controls the
      autocrine production of IGF-II and the subsequent phosphatidylinositol 3
      kinase/Akt signaling downstream of IGF-II in myogenesis. Here we report a
      regulatory loop connecting FoxO1 to the mTOR pathway. Inducible activation of a
      FoxO1 active mutant in the C2C12 mouse myoblasts blocks myogenic differentiation
      at an early stage and meanwhile leads to proteasome-dependent degradation of a
      specific subset of components in the mTOR signaling network, including mTOR,
      raptor, tuberous sclerosis complex 2, and S6 protein kinase 1. This function of
      FoxO1 requires new protein synthesis, consistent with the idea that a
      transcriptional target of FoxO1 may be responsible for the degradation of mTOR.
      We further show that active FoxO1 inhibits IGF-II expression at the
      transcriptional activation level, through the modulation of mTOR protein levels.
      Moreover, the addition of exogenous IGF-II fully rescues myocyte differentiation
      from FoxO inhibition. Taken together, we propose that the mTOR-IGF-II pathway is
      a major mediator of FoxO's inhibitory function in skeletal myogenesis.

PMID- 18079194
TI  - Abnormalities of insulin-like growth factor-I signaling and impaired cell
      proliferation in osteoblasts from subjects with osteoporosis.
AB  - IGF-I regulates bone acquisition and maintenance, even though the cellular
      targets and signaling pathways responsible for its action in human bone cells are
      poorly understood. Whether abnormalities in IGF-I action and signaling occur in
      human osteoblasts under conditions of net bone loss has not been determined.
      Herein we carried out a comparative analysis of IGF-I signaling in primary
      cultures of human osteoblasts from osteoporotic and control donors. In comparison
      with control cells, osteoporotic osteoblasts showed increased tyrosine
      phosphorylation of the IGF-I receptor in the basal state and blunted stimulation
      of receptor phosphorylation by IGF-I. Augmentation of basal IGF-I receptor
      phosphorylation was associated with coordinate increases in basal tyrosine
      phosphorylation of insulin receptor substrate (IRS)-2 and activation of Erk,
      which were also minimally responsive to IGF-I stimulation. By contrast,
      phosphorylation levels of IRS-1, Akt, and glycogen synthase kinase-3 were similar
      in the basal state in control and osteoporotic osteoblasts and showed marked
      increases after IGF-I stimulation in both cell populations, even though these
      responses were significantly lower in the osteoporotic osteoblasts. The IGF-I
      signaling abnormalities in osteoporotic osteoblasts were associated with reduced
      DNA synthesis both under basal conditions and after stimulation with IGF-I.
      Interestingly, treatment of the osteoporotic osteoblasts with the MAPK kinase
      inhibitor PD098059 reduced the elevated levels of Erk phosphorylation and
      increased basal DNA synthesis. Collectively, our data show that altered
      osteoblast proliferation in human osteoporosis may result from dysregulation of
      IGF-I receptor signaling, including constitutive activation of the IRS-2/Erk
      signaling pathway, which becomes unresponsive to IGF-I, and defective induction
      of the IRS-1/Akt signaling pathway.

PMID- 18079195
TI  - Cloning, expression, and functional characterization of relaxin receptor (leucine
      rich repeat-containing g protein-coupled receptor 7) splice variants from human
      fetal membranes.
AB  - The relaxin receptor [leucine-rich repeat-containing G protein-coupled receptor 7
      (LGR7)] belongs to the leucine-rich repeat containing G protein-coupled receptors
      subgroup C. Three new LGR7 splice variants have been cloned from the human fetal
      membranes and shown to be truncated versions of the full-length receptor, encoded
      by different lengths of the extracellular domain. The expression of their mRNAs
      has been confirmed by both qualitative and quantitative PCR and shown to be
      higher in the chorion and decidua before, compared with after, spontaneous labor.
      When HEK293 cells were transfected with each LGR7 splice variant, their proteins
      were retained within the endoplasmic reticulum. However, the protein for the
      shortest variant was also secreted into the medium. We have characterized the
      intracellular functions and effects of these LGR7 variants on the function of the
      wild-type (WT)-LGR7. In coexpression studies, each splice variant interacted
      directly with the WT-LGR7 and exerted a dominant-negative effect on cAMP
      accumulation by the WT-LGR7 after relaxin treatment. This interaction resulted in
      the sequestration of the WT-LGR7 inside the cells by down-regulation of its
      maturation and cell surface delivery. The constitutive homodimerization of WT
      LGR7 has been shown here to take place in the endoplasmic reticulum, and the
      presence of any one of the splice variants decreased this by the formation of
      heterodimers with the WT-LGR7, supporting the view that homodimerization is a
      prerequisite for receptor trafficking to the cell surface. These data suggest
      that the dominant-negative effects of the LGR7 splice variants expressed in the
      chorion and decidua could be functionally significant in the peripartal period by
      inhibiting the function of WT-LGR7 and dampening the responsiveness of these
      tissues to endogenous relaxin.

PMID- 18079196
TI  - Norepinephrine suppresses gonadotropin-releasing hormone neuron excitability in
      the adult mouse.
AB  - Norepinephrine (NE) is considered to exert an important modulatory influence upon
      the activity of GnRH neurons. In the present study, we used a transgenic GnRH
      green fluorescent protein mouse model to examine the effects of NE on the
      electrical excitability of GnRH neurons in male and female mice. Gramicidin
      perforated patch recordings demonstrated that NE (10-100 mum) exerted a robust
      membrane hyperpolarization, with associated suppression of firing, in more than
      85% of male prepubertal and adult GnRH neurons (n = 25). The same hyperpolarizing
      action was observed in female GnRH neurons from diestrous (91%, n = 11),
      proestrous (50%, n = 14), estrous (77%, n = 13), and ovariectomized (82%, n = 11)
      mice. A subpopulation (<10%) of silent GnRH neurons in all groups responded to NE
      with hyperpolarization followed by the initiation of firing upon NE washout. The
      hyperpolarizing actions of NE were mimicked by alpha1-adrenergic (phenylephrine)
      and beta-adrenergic (isoproterenol) receptor agonists, but alpha2 receptor
      activation (guanabenz) had no effect. Approximately 75% of the NE-evoked
      hyperpolarization was blocked by the alpha1 receptor antagonist prazosin, and 75%
      of GnRH neurons responded to both phenylephrine and isoproterenol. These findings
      indicate that NE acts through both alpha1- and beta-adrenergic receptors located
      on the soma/dendrites of GnRH neurons to directly suppress their excitability
      throughout the estrous cycle and after ovariectomy. These data force a reanalysis
      of existing models explaining the effects of NE on gonadotropin secretion.

PMID- 18079197
TI  - Roles of Rho guanosine 5'-triphosphatase A, Rho kinases, and extracellular signal
      regulated kinase (1/2) in prostaglandin E2-mediated migration of first-trimester
      human extravillous trophoblast.
AB  - Prostaglandin (PG) E(2) may regulate invasiveness of human placenta because we
      previously reported stimulation of migration of placental trophoblasts by PGE(2)
      acting through PGE receptor (EP)-1 and activating calpain. RhoA GTPase and its
      important effector Rho kinase (ROCK) have also been previously shown to regulate
      trophoblast migration. Using immortalized HTR-8/SVneo trophoblast cells and first
      trimester human chorionic villus explant cultures on matrigel, we further
      examined the role of RhoA/ROCK and MAPK (ERK1/2) pathways on PGE(2)-mediated
      stimulation of trophoblast migration. Migration of cytotrophoblasts was shown to
      be inhibited by treatment of the trophoblast cell line and chorionic villus
      explants with either cell-permeable C3 transferase or selective RhoA small
      interfering RNA. These inhibitions were significantly mitigated by the addition
      of PGE(2), an EP1/EP3 agonist or an EP3/EP4 agonist, suggesting that RhoA plays
      an important role in trophoblast migration but may not be obligatory for PGE(2)
      action. Treatment of HTR-8/SVneo cells with nonselective ROCK inhibitor Y27632 or
      ROCK small interfering RNAs inhibited migration of these cells, which could not
      be rescued with PGE(2) or the other two EP agonists, suggesting the obligatory
      role of ROCK in PGE(2)-induced migratory response. Furthermore, U0126, an
      inhibitor of MAPK kinases MEK1 and MEK2, abrogated PGE(2)-induced migration of
      trophoblasts, and PGE(2) or the other two EP agonists stimulated ERK1/2
      activation in trophoblasts, which was not abrogated by pretreatment with C3
      transferase, indicating that ERK signaling pathway is an efficient alternate
      pathway for RhoA in PGE(2)-mediated migration of trophoblasts. These results
      suggest that ROCK and ERK1/2 play more important roles than RhoA in PGE(2)
      mediated migration stimulation of first-trimester trophoblasts.

PMID- 18079198
TI  - Dehydroepiandrosterone stimulates endothelial proliferation and angiogenesis
      through extracellular signal-regulated kinase 1/2-mediated mechanisms.
AB  - Dehydroepiandrosterone (DHEA) activates a plasma membrane receptor on vascular
      endothelial cells and phosphorylates ERK 1/2. We hypothesize that ERK1/2
      dependent vascular endothelial proliferation underlies part of the beneficial
      vascular effect of DHEA. DHEA (0.1-10 nm) activated ERK1/2 in bovine aortic
      endothelial cells (BAECs) by 15 min, causing nuclear translocation of
      phosphorylated ERK1/2 and phosphorylation of nuclear p90 ribosomal S6 kinase.
      ERK1/2 phosphorylation was dependent on plasma membrane-initiated activation of
      Gi/o proteins and the upstream MAPK kinase because the effect was seen with
      albumin-conjugated DHEA and was blocked by pertussis toxin or PD098059. A 15-min
      incubation of BAECs with 1 nm DHEA (or albumin-conjugated DHEA) increased
      endothelial proliferation by 30% at 24 h. This effect was not altered by
      inhibition of estrogen or androgen receptors or nitric oxide production. There
      was a similar effect of DHEA to increase endothelial migration. DHEA also
      increased the formation of primitive capillary tubes of BAECs in vitro in
      solubilized basement membrane. These rapid DHEA-induced effects were reversed by
      the inhibition of either Gi/o-proteins or ERK1/2. Additionally, DHEA enhanced
      angiogenesis in vivo in a chick embryo chorioallantoic membrane assay. These
      findings indicate that exposure to DHEA, at concentrations found in human blood,
      causes vascular endothelial proliferation by a plasma membrane-initiated activity
      that is Gi/o and ERK1/2 dependent. These data, along with previous findings,
      define an important vascular endothelial cell signaling pathway that is activated
      by DHEA and suggest that this steroid may play a role in vascular function.

PMID- 18079200
TI  - RFamide-related peptide gene is a melatonin-driven photoperiodic gene.
AB  - In seasonal species, various physiological processes including reproduction are
      organized by photoperiod via melatonin, but the mechanisms of melatonin action
      are still unknown. In birds, the peptide gonadotropin-inhibiting hormone (GnIH)
      has been shown to have inhibitory effects on reproductive activity and displays
      seasonal changes of expression. Here we present evidence in mammals that the gene
      orthologous to GnIH, the RFamide-related peptide (RFRP) gene, expressed in the
      mediobasal hypothalamus, is strongly regulated by the length of the photoperiod,
      via melatonin. The level of RFRP mRNA and the number of RFRP-immunoreactive cell
      bodies were reduced in sexually quiescent Syrian and Siberian hamsters acclimated
      to short-day photoperiod (SD) compared with sexually active animals maintained
      under long-day photoperiod (LD). This was contrasted in the laboratory Wistar
      rat, a non-photoperiodic breeder, in which no evidence for RFRP photoperiodic
      modulation was seen. In Syrian hamsters, the reduction of RFRP expression in SD
      was independent from secondary changes in gonadal steroids. By contrast, the
      photoperiodic variation of RFRP expression was abolished in pinealectomized
      hamsters, and injections of LD hamsters with melatonin for 60 d provoked
      inhibition of RFRP expression down to SD levels, indicating that the regulation
      is dependent on melatonin. Altogether, these results demonstrate that in these
      hamster species, the RFRP neurons are photoperiodically modulated via a melatonin
      dependent process. These observations raise questions on the role of RFRP as a
      general inhibitor of reproduction and evoke new perspectives for understanding
      how melatonin controls seasonal processes via hypothalamic targets.

PMID- 18079199
TI  - Rapid action of estrogens on intracellular calcium oscillations in primate
      luteinizing hormone-releasing hormone-1 neurons.
AB  - Feedback controls of estrogen in LHRH-1 neurons play a pivotal role in
      reproductive function. However, the mechanism of estrogen action in LHRH-1
      neurons is still unclear. In the present study, the effect of estrogens on
      intracellular calcium ([Ca(2+)](i)) oscillations in primate LHRH-1 neurons was
      examined. Application of 17beta-estradiol (E(2), 1 nm) for 10 min increased the
      frequency of [Ca(2+)](i) oscillations within a few minutes. E(2) also increased
      the frequency of [Ca(2+)](i) synchronization among LHRH-1 neurons. Similar E(2)
      effects on the frequency of [Ca(2+)](i) oscillations were observed under the
      presence of tetrodotoxin, indicating that estrogen appears to cause direct action
      on LHRH-1 neurons. Moreover, application of a nuclear membrane-impermeable
      estrogen dendrimer conjugate, not control dendrimer, resulted in a robust
      increase in the frequencies of [Ca(2+)](i) oscillations and synchronizations,
      indicating that effects estrogens on [Ca(2+)](i) oscillations and their
      synchronizations do not require their entry into the cell nucleus. Exposure of
      cells to E(2) in the presence of the estrogen receptor antagonist ICI 182,780 did
      not change the E(2)-induced increase in the frequency of [Ca(2+)](i) oscillations
      or the E(2)-induced increase in the synchronization frequency. Collectively,
      estrogens induce rapid, direct stimulatory actions through receptors located in
      the cell membrane/cytoplasm of primate LHRH-1 neurons, and this action of
      estrogens is mediated by an ICI 182,780-insensitive mechanism yet to be
      identified.

PMID- 18079201
TI  - Substrate-bound insulin-like growth factor (IGF)-I-IGF binding protein
      vitronectin-stimulated breast cell migration is enhanced by coactivation of the
      phosphatidylinositide 3-Kinase/AKT pathway by alphav-integrins and the IGF-I
      receptor.
AB  - IGF-I can bind to the extracellular matrix protein vitronectin (VN) through the
      involvement of IGF-binding proteins-2, -3, -4, and -5. Because IGF-I and VN have
      established roles in tumor cell dissemination, we were keen to investigate the
      functional consequences of the interaction of IGF-I, IGF binding proteins
      (IGFBPs), and VN in tumor cell biology. Hence, functional responses of MCF-7
      breast carcinoma cells and normal nontumorgenic MCF-10A mammary epithelial cells
      were investigated to allow side-by-side comparisons of these complexes in both
      cancerous and normal breast cells. We demonstrate that substrate-bound IGF-I
      IGFBP-VN complexes stimulate synergistic increases in cellular migration in both
      cell types. Studies using IGF-I analogs determined this stimulation to be
      dependent on both heterotrimeric IGF-I-IGFBP-VN complex formation and the
      involvement of the IGF-I receptor (IGF-IR). Furthermore, the enhanced cellular
      migration was abolished on incubation of MCF-7 and MCF-10A cells with function
      blocking antibodies directed at VN-binding integrins and the IGF-IR. Analysis of
      the signal transduction pathways underlying the enhanced cell migration revealed
      that the complexes stimulate a transient activation of the ERK/MAPK signaling
      pathway while simultaneously producing a sustained activation of the
      phosphatidylinositide 3-kinase/AKT pathway. Experiments using pharmacological
      inhibitors of these pathways determined a requirement for phosphatidylinositide 3
      kinase/AKT activation in the observed response. Overexpression of wild type and
      activated AKT further increases substrate-bound IGF-I-IGFBP-VN-stimulated
      migration. This study provides the first mechanistic insights into the action of
      IGF-I-IGFBP-VN complexes and adds further evidence to support the involvement of
      VN-binding integrins and their cooperativity with the IGF-IR in the promotion of
      tumor cell migration.

PMID- 18079202
TI  - Wnt pathway inhibitors are strongly down-regulated in pituitary tumors.
AB  - The etiology of sporadic pituitary tumors is currently unknown. The Wnt pathways
      have been implicated in the pathogenesis of a variety of human tumors, but the
      role of these pathways in pituitary tumors is unclear. Microarray analysis using
      the Affymetrix HG U133 plus 2.0 GeneChips identified four secreted frizzled
      related protein (sFRP) family members of Wnt pathway inhibitors that were
      differentially expressed in both nonfunctioning and clinically functioning
      pituitary tumors (n = 20) compared with normal pituitary controls (n = 3).
      Reduced tumor expression of Wnt inhibitory factor-1 (WIF1), sFRP2, and sFRP4 mRNA
      was confirmed by real-time quantitative RT-PCR (P <0.001 and P = 0.002 and 0.013,
      respectively) in all pituitary subtypes. Hypermethylation of the WIF1 promoter
      was present in 88% of the pituitary tumors (n = 41). Seventy-six percent of
      pituitary tumors demonstrated absent or weak cytoplasmic WIF1 staining by
      immunohistochemistry (n = 41), although preserved staining was seen in some
      functioning tumors, with strong staining in 92% of normal pituitary controls (n =
      13). The Wnt pathway target gene cyclin D1 was found to be up-regulated
      specifically in the nonfunctioning pituitary tumors compared with controls at
      both mRNA and protein level, supportive of activation of the Wnt-beta-catenin
      pathway. Nuclear accumulation of beta-catenin, however, was not observed in any
      pituitary tumors (n = 70). By transfecting GH3 cells with WIF1, decreased cell
      proliferation and colony formation was observed compared with empty vector
      controls. In conclusion, our data suggest that WIF1 may be a tumor suppressor,
      specifically in nonfunctioning pituitary tumors, and that the Wnt pathways are
      important in pituitary tumorigenesis.

PMID- 18079203
TI  - Stress mediators regulate brain prostaglandin synthesis and peroxisome
      proliferator-activated receptor-gamma activation after stress in rats.
AB  - Stress exposure leads to oxidative/nitrosative and neuroinflammatory changes that
      have been shown to be regulated by antiinflammatory pathways in the brain. In
      particular, acute restraint stress is followed by cyclooxygenase (COX)-2 up
      regulation and subsequent proinflammatory prostaglandin (PG) E2 release in rat
      brain cortex. Concomitantly, the synthesis of the antiinflammatory prostaglandin
      15d-PGJ(2) and the activation of its nuclear target the peroxisome proliferator
      activated receptor (PPAR)-gamma are also produced. This study aimed to determine
      the possible role of the main stress mediators: catecholamines, glucocorticoids,
      and excitatory amino acids (glutamate) in the above-mentioned stress-related
      effects. By using specific pharmacological tools, our results show that the main
      mediators of the stress response are implicated in the regulation of
      prostaglandin synthesis and PPARgamma activation in rat brain cortex described
      after acute restraint stress exposure. Pharmacological inhibition (predominantly
      through beta-adrenergic receptor) of the stress-released catecholamines in the
      central nervous system regulates 15d-PGJ(2) and PGE(2) synthesis, by reducing COX
      2 overexpression, and reduces PPARgamma activation. Stress-produced
      glucocorticoids carry out their effects on prostaglandin synthesis through their
      interaction with mineralocorticoid and glucocorticoid receptors to a very similar
      degree. However, in the case of PPARgamma regulation, only the actions through
      the glucocorticoid receptor seem to be relevant. Finally, the selective blockade
      of the N-methyl-d-aspartate type of glutamate receptor after stress also
      negatively regulates 15d-PGJ(2) and PGE(2) production by COX-2 down-regulation
      and decrease in PPARgamma transcriptional activity and expression. In conclusion,
      we show here that the main stress mediators, catecholamines, GCs, and glutamate,
      concomitantly regulate the activation of proinflammatory and antiinflammatory
      pathways in a possible coregulatory mechanism of the inflammatory process induced
      in rat brain cortex by acute restraint stress exposure.

PMID- 18079205
TI  - Disruption of growth hormone signaling retards prostate carcinogenesis in the
      Probasin/TAg rat.
AB  - We asked whether down-regulation of GH signaling could block carcinogenesis in
      the Probasin/TAg rat, a model of aggressive prostate cancer. The Spontaneous
      Dwarf rat, which lacks GH due to a mutation (dr) in its GH gene, was crossed with
      the Probasin/TAg rat, which develops prostate carcinomas at 100% incidence by 15
      wk of age. Progeny were heterozygous for the TAg oncogene and homozygous for
      either the wild-type GH gene (TAg/Gh(+/+)) or the dr mutation (TAg/Gh(dr/dr)).
      Prostate tumor incidence and burden were significantly reduced, and tumor latency
      was delayed in TAg/Gh(dr/dr) rats relative to TAg/Gh(+/+) controls. At 25 wk of
      age, loss of GH resulted in a 20 and 80% decrease in the area of microinvasive
      carcinoma in the dorsal and lateral lobes, respectively. By 52 wk of age,
      invasive prostate adenocarcinomas were observed in all TAg/Gh(+/+) rats, whereas
      the majority of TAg/Gh(dr/dr) did not develop invasive tumors. Suppression of
      carcinogenesis could not be attributed to alterations in prostate expression of
      TAg or androgen receptor or changes in serum testosterone levels. As
      carcinogenesis progressed in TAg/Gh(+/+) rats, prostate GHR mRNA and protein
      expression increased significantly, but prostate IGF-I receptor mRNA and protein
      levels dropped. Furthermore, serum IGF-I and prostate IGF-I levels did not change
      significantly over the course of carcinogenesis. These findings suggest that GH
      plays a dominant role in progression from latent to malignant prostate cancer
      driven by the powerful probasin/TAg fusion gene in rats and suggest that GH
      antagonists may be effective at treating human prostate cancer.

PMID- 18079206
TI  - Corticotropin-releasing hormone (CRH) depresses n-methyl-D-aspartate receptor
      mediated current in cultured rat hippocampal neurons via CRH receptor type 1.
AB  - CRH, the primary regulator of the neuroendocrine responses to stress, has been
      shown to modulate synaptic efficacy and the process of learning and memory in
      hippocampus. However, effects of CRH on N-methyl-d-aspartate (NMDA) receptor, the
      key receptor for synaptic plasticity, remain unclear. In primary cultured
      hippocampal neurons, using the technique of whole-cell patch-clamp recordings, we
      found that CRH (1 pmol/liter to 10 nmol/liter) inhibited NMDA-induced currents in
      a dose-dependent manner. This effect was reversed by the CRH receptor type 1
      (CRHR1) antagonist antalarmin but not by the CRHR2 antagonist astressin-2B,
      suggesting that CRHR1 mediated the inhibitory effect of CRH. Investigations on
      the signaling pathways of CRH showed that CRH dose-dependently induced
      phosphorylated phospholipase C (PLC)-beta3 expression and increased intracellular
      cAMP content in these cells. Blocking PLC activity with U73122 prevented CRH
      induced depression of NMDA current, whereas blocking protein kinase A (H89) and
      adenylate cyclase (SQ22536) failed to affect the CRH-induced depression of NMDA
      current. Application of inositol-1,4,5-triphosphate receptor (IP(3)R) antagonist,
      Ca(2+) chelators or protein kinase C (PKC) inhibitors also mainly blocked CRH
      induced depression of NMDA currents, suggesting involvement of
      PLC/IP(3)R/Ca(2+)and PLC/PKC signaling pathways in CRH down-regulation of NMDA
      receptors. Our results suggest that CRH may exert neuromodulatory actions on
      hippocampus through regulating NMDA receptor function.

PMID- 18079204
TI  - Synergistic induction of follicle-stimulating hormone beta-subunit gene
      expression by gonadal steroid hormone receptors and Smad proteins.
AB  - LH and FSH play crucial roles in mammalian reproduction by mediating
      steroidogenesis and gametogenesis. Gonadal steroid hormones influence
      gonadotropin production via feedback to the hypothalamus and pituitary. We
      previously demonstrated that progesterone and testosterone can stimulate
      expression of the FSH beta-subunit gene in immortalized gonadotrope-derived
      LbetaT2 cells. Herein, we investigate how these gonadal steroids modulate activin
      signaling in the gonadotrope. Cotreatment of LbetaT2 cells or mouse primary
      pituitary cells with steroids and activin results in a synergistic induction of
      FSHbeta gene expression. This synergy decreases when DNA-binding mutations are
      introduced into the steroid receptors or when mutations that reduce steroid
      hormone responsiveness are introduced into the FSHbeta promoter, indicating that
      synergy requires direct DNA binding of the steroid receptors. Furthermore,
      classical activin signaling via Smad proteins is necessary for this synergy. In
      addition, these steroid receptors physically interact with Smads and are
      sufficient for the synergism to occur on the FSHbeta promoter. Disruption of Smad
      binding to the promoter with a Smad protein lacking the DNA-binding domain or an
      FSHbeta promoter containing mutated activin-response elements prevents the
      synergistic enhancement of FSHbeta transcription. Collectively, our data
      demonstrate that the molecular mechanism for gonadal steroid hormone action on
      the FSHbeta promoter involves cross-talk between the steroid and activin
      signaling pathways. They also reveal that this synergism requires binding of both
      the steroid receptors and Smad proteins to their cognate DNA-binding elements and
      likely involves a direct protein-protein interaction between the two types of
      transcription factors.

PMID- 18079207
TI  - Resistance to the nitric oxide/cyclic guanosine 5'-monophosphate/protein kinase G
      pathway in vascular smooth muscle cells from the obese Zucker rat, a classical
      animal model of insulin resistance: role of oxidative stress.
AB  - Some in vivo and ex vivo studies demonstrated a resistance to the vasodilating
      effects of nitric oxide (NO) in insulin-resistant states and, in particular,
      obese Zucker rats (OZR). To evaluate the biochemical basis of this phenomenon, we
      aimed to identify defects of the NO/cGMP/cGMP-dependent protein kinase (PKG)
      pathway in cultured vascular smooth muscle cells (VSMCs) from OZR and lean Zucker
      rats (LZR) by measuring: 1) NO donor ability to increase cGMP in the absence and
      presence of inhibitors of soluble guanylate cyclase (sGC) and phosphodiesterases
      (PDEs); 2) NO and cGMP ability to induce, via PKG, vasodilator-stimulated
      phosphoprotein (VASP) phosphorylation at serine 239 and PDE5 activity; 3) protein
      expression of sGC, PKG, total VASP, and PDE5; 4) superoxide anion concentrations
      and ability of antioxidants (superoxide dismutase+catalase and amifostine) to
      influence the NO/cGMP/PKG pathway activation; and 5) hydrogen peroxide influence
      on PDE5 activity and VASP phosphorylation. VSMCs from OZR vs. LZR showed: 1)
      baseline cGMP concentrations higher, at least in part owing to reduced catabolism
      by PDEs; 2) impairment of NO donor ability to increase cGMP, even in the presence
      of PDE inhibitors, suggesting a defect in the NO-induced sGC activation; 3)
      reduction of NO and cGMP ability to activate PKG, indicated by the impaired
      ability to phosphorylate VASP at serine 239 and to increase PDE5 activity via
      PKG; 4) similar baseline protein expression of sGC, PKG, total VASP, and PDE5;
      and 5) higher levels of superoxide anion. Antioxidants partially prevented the
      defects of the NO/cGMP/PKG pathway observed in VSMCs from OZR, which were
      reproduced by hydrogen peroxide in VSMCs from LZR, suggesting the pivotal role of
      oxidative stress.

PMID- 18079208
TI  - Aldosterone induces superoxide generation via Rac1 activation in endothelial
      cells.
AB  - Currently, aldosterone is believed to be involved in the development of
      cardiovascular injury as a potential cardiovascular risk hormone. However, its
      exact cellular mechanisms remain obscure. This study was undertaken to examine
      the effect of aldosterone on superoxide production in cultured rat aortic
      endothelial cells with possible involvement of the small GTP-binding (G) protein
      Rac1. The aldosterone levels showed a time-dependent (6-24 h) and dose-dependent
      (10(-8) to 10(-6) m) increase in superoxide generation, whose effect was
      abolished by mineralocorticoid receptor antagonist (eplerenone), Src inhibitor
      (PP2), and reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase
      inhibitor (apocynin). Aldosterone activated NADP(H) oxidase and Rac1, whose
      effects were abolished by eplerenone. The aldosterone-induced superoxide
      generation was abolished either by nonselective small G protein inhibitor
      (Clostridium difficile toxin A) or dominant-negative Rac1. Dominant-negative Rac1
      also inhibited aldosterone-induced ACE gene expression. Thus, the present study
      is the first to demonstrate that aldosterone induces superoxide generation via
      mineralocorticoid receptor-mediated activation of NAD(P)H-oxidase and Rac1 in
      endothelial cells, thereby contributing to the development of aldosterone-induced
      vascular injury.

PMID- 18079209
TI  - Interleukin (IL)-17A stimulates IL-8 secretion, cyclooxygensase-2 expression, and
      cell proliferation of endometriotic stromal cells.
AB  - IL-17A is secreted from Th17 cells, a discovery leading to revision of the
      mechanism underlying the role of Th1/Th2 in the immune response. Strong evidence
      suggests that immune responses associated with inflammation are involved in the
      pathogenesis of endometriosis. In the present study, we first demonstrated that
      the presence of Th17 cells in peritoneal fluid of endometriotic women by flow
      cytometric analysis and IL-17A-positive cells in endometriotic tissues by
      immunohistochemistry. To investigate the role of IL-17A in the development of
      endometriosis, we then studied the effect of IL-17A on IL-8 production,
      cyclooxygensase-2 expression, and cell proliferation of cultured endometriotic
      stromal cells (ESCs). IL-17A enhanced IL-8 secretion from ESCs in a dose
      dependent manner. The IL-17A-induced secretion of IL-8 from ESCs was suppressed
      by anti-IL-17 receptor A antibodies or inhibitors of p38 MAPK, p42/44 MAPK, and
      stress-activated protein kinase/c-Jun N-terminal kinase. Addition of TNFalpha
      synergistically increased IL-17A-induced IL-8 secretion from ESCs. IL-17A also
      enhanced the expression of cyclooxygensase-2 mRNA and proliferation of ESCs. IL
      17A may play a role in the development of endometriosis by stimulating
      inflammatory responses and proliferation of ESCs.

PMID- 18079210
TI  - Loss of function in virus-specific lung effector T cells is independent of
      infection.
AB  - Recently, several studies, including those with respiratory syncytial virus,
      mouse pneumovirus, and simian virus 5, have reported that virus-specific CD8+
      effector cells entering the lung as a result of respiratory infection undergo
      significant loss of function. The impaired function in these cells has been
      proposed to be the result of infection-induced changes in the lung. Although
      virus-specific effects may contribute to regulation of T cells in the lung, the
      findings from this study provide evidence that the basal lung environment is
      sufficient to promote loss of function in effector cells. Loss of function occurs
      within 48 h of entry into the lung and is most evident in cells residing in the
      lung parenchyma. These findings suggest an additional paradigm for the
      immunoregulation of effector cells that enter the lung as a result of virus
      infection.

PMID- 18079211
TI  - Dr. Friedrich Wegener and the ACCP, Revisited.

PMID- 18079212
TI  - Proteases in COPD: a critical pathway to injury.

PMID- 18079213
TI  - Sepsis and sex: can we look beyond our hormones?

PMID- 18079214
TI  - Oral vs IV corticosteroids for in-hospital treatment of COPD exacerbations.

PMID- 18079215
TI  - Hypercapnic obstructive sleep apnea: an underappreciated marker of severity.

PMID- 18079216
TI  - Understanding COPD hospitalizations: the devil is always in the details!

PMID- 18079217
TI  - Transcutaneous PCO2 monitoring during initiation of noninvasive ventilation.
AB  - BACKGROUND: To assess the efficacy of transcutaneous Pco2 (Ptcco2) measurements
      for monitoring alveolar ventilation in patients requiring noninvasive positive
      pressure ventilation (NPPV). METHODS: In a prospective study on method agreement
      pairs of Paco2 and Ptcco2 (SenTec Digital Monitor; SenTec AG; Therwil,
      Switzerland), measurements were performed every 10 min during the establishment
      of NPPV over a 4-h period in 10 patients (8 patients with COPD) presenting with
      acute-on-chronic hypercapnic respiratory failure, thus providing 250 pairs of
      measurement. RESULTS: Mean (+/- SD) Paco2 decreased from 67.2 +/- 11.9 mm Hg
      (Ptcco2, 65.5 +/- 13.9 mm Hg) to 54.6 +/- 8.8 mm Hg (Ptcco2, 47.8 +/- 8.8 mm Hg),
      and mean pH increased from 7.36 +/- 0.03 to 7.44 +/- 0.04. Following Ptcco2
      assessment, Ptcco2 in the ensuing 2-min period was the strongest predictor for
      Paco2 compared to Ptcco2 in the ensuing 5-min period and to real-time
      measurements. Ptcco2 was highly correlated with Paco2 (r = 0.916; p < 0.001), as
      determined by linear regression analysis. The mean difference between Paco2 and
      Ptcco2 was 4.6 mm Hg, and the limits of agreement (bias +/- 1.96 SDs) ranged from
      -3.9 to 13.2 mm Hg, following the Bland and Altman analysis. Retrospective drift
      correction produced an even higher correlation (r = 0.956; p < 0.001) with lower
      limits of agreement (-1.7 to 7.5 mm Hg). CONCLUSIONS: Ptcco2 measurements provide
      a sensitive, continuous, and noninvasive method for monitoring alveolar
      ventilation in patients who are receiving short-term NPPV therapy. Drift
      correction of Ptcco2 measurements improves the accuracy of Ptcco2 monitoring
      compared to the "gold standard" Paco2 assessment. A lag time of approximately 2
      min is present for reliable Ptcco2 values compared to Paco2 values. However,
      individual variance between Paco2 and Ptcco2 cannot be excluded. TRIAL
      REGISTRATION: www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html
      Identifier:UKF001271.

PMID- 18079218
TI  - Daytime hypercapnia in obstructive sleep apnea syndrome.
AB  - BACKGROUND: The pathogenesis of daytime hypercapnia (Paco2 >or= 45 mm Hg) may be
      directly linked to the existence of obstructive sleep apnea syndrome (OSAS) per
      se, although only some patients with OSAS exhibit daytime hypercapnia. OBJECTIVE:
      To investigate the prevalence of daytime hypercapnia in patients with OSAS; the
      association of daytime hypercapnia and obesity, obstructive airflow limitation,
      restrictive lung impairment, and severity of sleep apnea; and the response to
      continuous positive airway pressure (CPAP) therapy in a subset of subjects.
      METHODS: The study involved 1,227 patients with OSAS who visited a sleep clinic
      and were examined using polysomnography. As for the response to CPAP therapy, the
      patients were considered good responders if their daytime Paco2 decreased >or= 5
      mm Hg and poor responders if it decreased < 5 mm Hg. RESULTS: Fourteen percent
      (168 of 1,227 patients) exhibited daytime hypercapnia. These patients had
      significantly higher body mass index (BMI) and apnea-hypopnea index (AHI) values
      compared with normocapnic patients, while percentage of predicted vital capacity
      (%VC) and FEV(1)/FVC ratio did not differ between the two groups. Logistic
      regression analysis showed that only AHI was a predictor of daytime hypercapnia
      (p < 0.0001), while BMI (p = 0.051) and %VC (p = 0.062) were borderline
      predictors of daytime hypercapnia. Daytime hypercapnia was corrected in some
      patients (51%, 19 of 37 patients) with severe OSAS after 3 months of CPAP
      therapy. CONCLUSION: The pathogenesis of daytime hypercapnia may be directly
      linked to sleep apnea in a subgroup of patients with OSAS.

PMID- 18079219
TI  - Efficacy of adaptive servoventilation in treatment of complex and central sleep
      apnea syndromes.
AB  - BACKGROUND: Complex sleep apnea syndrome (CompSAS) is recognized by the
      concurrence of mixed or obstructive events with central apneas, the latter
      predominating on exposure to continuous positive airway pressure (CPAP).
      Treatment of CompSAS or central sleep apnea (CSA) syndrome with adaptive
      servoventilation (ASV) is now an option, but no large series exist describing the
      application and effectiveness of ASV. METHODS: Retrospective chart review of the
      first 100 patients who underwent polysomnography using ASV at Mayo Clinic Sleep
      Center. RESULTS: ASV titration was performed for CompSAS (63%), CSA (22%), or
      CSA/Cheyne Stokes breathing patterns (15%). The median diagnostic sleep apnea
      hypopnea index (AHI) was 48 events per hour (range, 24 to 62). With CPAP,
      obstructive apneas decreased, but the appearance of central apneas maintained the
      AHI at 31 events per hour (range, 17 to 47) [p = 0.02]. With bilevel positive
      airway pressure (BPAP) in spontaneous mode, AHI trended toward worsening vs
      baseline, with a median of 75 events per hour (range, 46 to 111) [p = 0.055].
      BPAP with a backup rate improved the AHI to 15 events per hour (range, 11 to 31)
      [p = 0.002]. Use of ASV dramatically improved the AHI to a mean of 5 events per
      hour (range, 1 to 11) vs baseline and vs CPAP (p < 0.0001). ASV also resulted in
      an increase in rapid eye movement sleep vs baseline and CPAP (18% vs 12% and 10%,
      respectively; p < 0.0001). Overall, 64 patients responded to the ASV treatment
      with a mean AHI < 10 events per hour. Of the 44 successful survey follow-up
      patients contacted, 32 patients reported some improvement in sleep quality.
      CONCLUSION: The ASV device appears to be an effective treatment of both CompSAS
      and CSA syndromes that are resistant to CPAP.

PMID- 18079220
TI  - Obstructive sleep apnea and resistant hypertension: a case-control study.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has been linked to resistant
      hypertension, but the magnitude of this association and its independence of
      confounding have not been established. METHODS: Case patients were 63 patients
      with resistant hypertension (BP >or= 140/90 mm Hg using at least three BP
      lowering drugs, including a diuretic), and control subjects were 63 patients with
      controlled BP receiving drug treatment. The primary outcome was the frequency of
      OSAS (apnea-hypopnea index [AHI] >or= 10 episodes per hour) determined with a
      portable home monitor. The comparison of AHI episodes in patients truly
      normotensive, truly hypertensive, and in patients with white coat or masked
      hypertension, based on BP determined at office and by ambulatory BP monitoring
      (ABPM) was a secondary outcome. RESULTS: Case patients and control subjects were
      well matched for confounding factors. OSAS was present in 45 case patients (71%)
      and in 24 control subjects (38%) [p < 0.001]. In a logistic regression model,
      OSAS was strongly and independently associated with resistant hypertension (odds
      ratio, 4.8; 95% confidence interval, 2.0 to 11.7). The AHI of case patients with
      normal BP in ABPM (white coat hypertension) and control subjects with abnormal BP
      in ABPM (masked hypertension) was intermediate between the AHI of individuals
      with normal and abnormal BP measures in both settings (p < 0.001). CONCLUSIONS:
      The magnitude and independence of the risk of OSAS for resistant hypertension
      strengthen the concept that OSAS is a risk factor for resistant hypertension.
      Comorbid OSAS should be considered in patients with resistant hypertension.

PMID- 18079221
TI  - Effects of montelukast treatment and withdrawal on fractional exhaled nitric
      oxide and lung function in children with asthma.
AB  - BACKGROUND: Leukotriene receptor antagonists (LTRAs) reduce fractional exhaled
      nitric oxide (Feno) concentrations in children with asthma, but the effect of
      LTRA withdrawal on Feno and lung function is unknown. We aimed to study the
      effect of treatment and withdrawal of montelukast, a LTRA, on airway inflammation
      as reflected by Feno and lung function in children with asthma. METHODS: A double
      blind, randomized, placebo controlled, parallel group study was undertaken in 14
      atopic children with mild persistent asthma who were treated with oral
      montelukast (5 mg/d for 4 weeks) and 12 atopic children with mild persistent
      asthma who received matching placebo. A follow-up visit was performed 2 weeks
      after montelukast or placebo withdrawal. RESULTS: Montelukast reduced Feno
      concentrations by 17% (p = 0.067), an effect that was more pronounced (35%) [p =
      0.0029] when children with seasonal atopy who were exposed to relevant allergens
      during the treatment phase were excluded from analysis (n = 3). Compared to those
      at the end of treatment, Feno concentrations were increased 2 weeks after
      montelukast withdrawal (p = 0.023) concomitant with a reduction in absolute
      FEV(1) values (p = 0.011), FEV(1) percentage of predicted values (p = 0.006),
      FEV(1)/FVC ratio (p = 0.002), and forced expiratory flow at 25% to 75% of FVC
      values (p = 0.021). These changes were not observed in the placebo group.
      CONCLUSIONS: LTRAs reduce Feno concentrations in children with asthma, and
      withdrawal can result in increased Feno values and worsening of lung function in
      children with asthma.

PMID- 18079222
TI  - Risk factors associated with persistent airflow limitation in severe or difficult
      to-treat asthma: insights from the TENOR study.
AB  - BACKGROUND: The Epidemiology and Natural History of Asthma: Outcomes and
      Treatment Regimens study is among the largest to assess persistent airflow
      limitation and the first to evaluate a wide range of potential risk factors in
      high-risk patients with severe or difficult-to-treat asthma. A better
      understanding is needed regarding factors associated with persistent airway
      obstruction; this study was performed to determine demographic and clinical
      characteristics associated with persistent airflow limitation. METHODS: Data from
      adult patients (>or= 18 years old) with severe or difficult-to-treat asthma were
      evaluated. Patients with COPD, obesity with a restrictive respiratory pattern, or
      a >or= 30 pack-year history of smoking were excluded. Patients with persistent
      airflow limitation (postbronchodilator FEV1/FVC ratio <or= 70% at two annual
      consecutive visits) and normal postbronchodilator FEV1/FVC ratio (75 to 85%) were
      compared. Multivariate analysis identified factors independently associated with
      persistent airflow limitation. RESULTS: Of 1,017 patients, 612 patients (60%)
      showed evidence of persistent airflow limitation. Risk factors were as follows:
      older age (odds ratio [OR] per 10 years, 1.4; 95% confidence interval [CI], 1.3
      to 1.6); male gender (OR, 4.5; 95% CI, 2.3 to 8.5); black ethnicity (OR, 2.2; 95%
      CI, 1.3 to 3.8); current or past smoking (OR, 3.9; 95% CI, 1.8 to 8.6; and OR,
      1.6; 95% CI, 1.2 to 2.3, respectively); aspirin sensitivity (OR, 1.5; 95% CI, 1.0
      to 2.4); and longer asthma duration (OR per 10 years, 1.6; 95% CI, 1.4 to 1.8).
      Protective factors were Hispanic ethnicity, higher education, family history of
      atopic dermatitis, pet(s) in the home, and dust sensitivity. CONCLUSIONS:
      Persistent airflow limitation is prevalent in patients with severe or difficult
      to-treat asthma and is associated with identifiable clinical and demographic
      characteristics.

PMID- 18079223
TI  - Low-molecular-weight heparin inhibits hypoxic pulmonary hypertension and vascular
      remodeling in guinea pigs.
AB  - RATIONALE: We have shown previously that antiproliferative unfractionated
      heparins block hypoxia-induced pulmonary arterial hypertension (PAH) and vascular
      remodeling, and hypothesized that low-molecular-weight heparins (LMWHs) would
      too. OBJECTIVES: To determine the potential role and mechanisms of dalteparin and
      enoxaparin (two LMWHs) in inhibiting hypoxic PAH and vascular remodeling.
      METHODS: Male Hartley guinea pigs were exposed for 10 days to normobaric 10%
      oxygen with dalteparin (5 mg/kg), enoxaparin (5 mg/kg), or with an equivalent
      volume of normal saline solution. Normoxic control animals (n = 5) received room
      air for 10 days. Bovine pulmonary artery smooth-muscle cells (PASMCs) were grown
      in 10% fetal bovine serum without heparin, with dalteparin (1 microg/mL) or with
      enoxaparin (1 microg/mL). MEASUREMENTS: Pulmonary arterial pressure (PAP),
      cardiac index, right ventricular heart weight divided by left ventricular plus
      septum weight (RV/LV+S), hematocrit, percentage of wall thickness of intraacinar
      vessels (%WT-IA), percentage of wall thickness of terminal bronchiole vessels
      (%WT-TA), and the percentage of thick-walled vessels (%Thick) were determined. In
      PASMCs, expression of p27 and cell growth were compared because in mice whole
      heparin depends on p27 for its antiproliferative action. MAIN RESULTS: In hypoxic
      animals, hematocrit, PAP, total pulmonary vascular resistance index, RV/LV+S, %WT
      IA, %WT-TA, and %Thick all rose significantly vs normoxic control animals (p <
      0.05); cardiac index was unchanged. Dalteparin but not enoxaparin significantly
      reduced PAP, total pulmonary vascular resistance index, and RV/LV + S (p < 0.05
      vs hypoxia alone); inhibited PASMC growth; and upregulated p27 expression.
      Enoxaparin moderately reduced vascular remodeling, which did not translate into
      less pulmonary hypertension. CONCLUSIONS: Not all LMWHs are the same. Dalteparin
      was more effective than enoxaparin in inhibiting pulmonary hypertension and
      vascular remodeling in hypoxic guinea pigs.

PMID- 18079224
TI  - Relationship of soluble CD40 ligand to vascular endothelial growth factor,
      angiopoietins, and tissue factor in atrial fibrillation: a link among platelet
      activation, angiogenesis, and thrombosis?
AB  - BACKGROUND: The precise pathophysiologic processes underlying the prothrombotic
      or hypercoagulable state in patients with atrial fibrillation (AF) remain
      uncertain. We hypothesized a relationship among abnormal platelet activation,
      angiogenic factors, and coagulation, thereby contributing to increased
      thrombogenecity. METHODS: Plasma levels of soluble CD40 ligand (sCD40L [an index
      of platelet activation]) and tissue factor (TF [an index of coagulation]), as
      well as the angiogenic factors, vascular endothelial growth factor (VEGF),
      angiopoietin (Ang)-1, and Ang-2, were measured by enzyme-linked immunosorbent
      assay in 59 patients with chronic AF. Data were compared to 40 age-matched and
      sex-matched healthy control subjects who were in sinus rhythm. RESULTS: AF
      patients had significantly higher levels of sCD40L (p = 0.038), VEGF (p = 0.023),
      and Ang-2 (p < 0.001), but not Ang-1 (p = 0.363), compared to control subjects.
      In non-anticoagulated AF patients (n = 28), TF levels were also higher (p =
      0.043), in addition to high sCD40L, VEGF, and Ang-2, compared to control
      subjects. Among AF patients, sCD40L levels correlated strongly with levels of
      VEGF (r = 0.919; p < 0.001) and Ang-2 (r = 0.546; p = 0.002). VEGF levels were
      significantly correlated with levels of Ang-2 (r = 0.490; p < 0.001) and TF (r =
      0.298; p = 0.044). In multivariate regression analysis, sCD40L levels were
      independently associated with levels of VEGF (p = 0.003) and Ang-2 (p = 0.005).
      CONCLUSIONS: Plasma levels of sCD40L are elevated in patients with AF, and are
      related to levels of VEGF, Ang-2, and TF. This interaction among platelets,
      angiogenic markers, and TF may play a role in the generation of the prothrombotic
      state associated with AF.

PMID- 18079225
TI  - Effects of percutaneous coronary intervention on peripheral venous blood
      circulating endothelial cells and plasma indices of endothelial
      damage/dysfunction.
AB  - BACKGROUND: The relationship between endothelial damage/dysfunction and coronary
      artery disease is well recognized. However, the effects of percutaneous coronary
      intervention (PCI) [stenting/angioplasty] on circulating markers of endothelial
      damage/dysfunction (eg, von Willebrand factor [vWF], soluble E-selectin [sEsel]
      levels, and more recently circulating endothelial cells [CECs]) has been less
      well defined. AIMS AND METHODS: We investigated the effects of both diagnostic
      coronary angiography (CA) [n = 15; blood sampling immediately before CA and 15
      min after CA] and PCI (n = 38; blood sampling before PCI, 15 min after PCI, and
      24 h after PCI) on levels of CECs, vWF, and sEsel across comparable patient
      groups. We also included a cohort of comparable healthy control subjects in order
      to compare baseline levels of three endothelial markers. RESULTS: There were no
      differences in baseline levels of CECs, vWF, or sEsel between the three study
      groups (healthy control subjects, CA, PCI; all p = not significant). Following CA
      (before to 15 min after), there were no significant changes in vWF and CECs (p =
      not significant). Following PCI, there were significant increases observed at 15
      min after PCI and at 24 h after PCI (when compared with pre-PCI levels) in CECs
      (p = 0.0006), vWF (p = 0.007), and sEsel (p = 0.024). CONCLUSION: We observed
      significant increases in three endothelial markers (CECs, vWF, and sEsel) with
      elective PCI but not CA. This is in keeping with endothelial damage/dysfunction
      following PCI.

PMID- 18079226
TI  - Assessing the relationship between lung cancer risk and emphysema detected on low
      dose CT of the chest.
AB  - RATIONALE: Identification of risk factors for lung cancer can help in selecting
      patients who may benefit the most from smoking cessation interventions, early
      detection, or chemoprevention. OBJECTIVE: To evaluate whether the presence of
      emphysema on low-radiation-dose CT (LDCT) of the chest is an independent risk
      factor for lung cancer. METHODS: The study used data from a prospective cohort of
      1,166 former and current smokers participating in a lung cancer screening study.
      All individuals underwent a baseline LDCT and spirometry followed by yearly
      repeat LDCT studies. The incidence density of lung cancer among patients with and
      without emphysema on LDCT was estimated. Stratified and multiple regression
      analyses were used to assess whether emphysema is an independent risk factor for
      lung cancer after adjusting for age, gender, smoking history, and the presence of
      airway obstruction on spirometry. RESULTS: On univariate analysis, the incidence
      density of lung cancer among individuals with and without emphysema on LDCT was
      25.0 per 1,000 person-years and 7.5 per 1,000 person-years, respectively (risk
      ratio [RR], 3.33; 95% confidence interval [CI], 1.41 to 7.85). Emphysema was also
      associated with increased risk of lung cancer when the analysis was limited to
      individuals without airway obstruction on spirometry (RR, 4.33; 95% CI, 1.04 to
      18.16). Multivariate analysis showed that the presence of emphysema (RR, 2.51;
      95% CI, 1.01 to 6.23) on LDCT but not airway obstruction (RR, 2.10; 95% CI, 0.79
      to 5.58) was associated with increased risk of lung cancer after adjusting for
      potential cofounders. CONCLUSIONS: Results suggest that the presence of emphysema
      on LDCT is an independent risk factor for lung cancer.

PMID- 18079227
TI  - Clinical/pathologic correlations in 553 patients with primary centrilobular
      findings on high-resolution CT scan of the thorax.
AB  - BACKGROUND: Clinical/pathologic correlations in patients with high-resolution CT
      (HRCT) scan findings presenting with two patterns of centrilobular opacity remain
      unclear. METHODS: Chest HRCT scans in 553 patients with predominant centrilobular
      opacities or preferential centrilobular disease were retrospectively evaluated.
      In 141 patients who underwent biopsy, CT scan images were compared with actual
      specimens. RESULTS: Centrilobular nodules with a tree-in-bud appearance and
      bronchial wall thickening were observed in most patients who were carriers of
      human T-lymphotropic virus type 1 (88 patients and 57 of 99 patients,
      respectively), Mycoplasma pneumoniae pneumonia (44 patients and 45 of 52
      patients, respectively), Mycobacterium tuberculosis (38 patients and 37 of 52
      patients, respectively), Mycobacterium avium-intracellulare complex (22 patients
      and 27 of 37 patients, respectively), Mycobacterium kansasii (27 patients and 19
      of 33 patients, respectively), allergic bronchopulmonary aspergillosis (6
      patients and 7 of 9 patients, respectively), diffuse panbronchiolitis (12
      patients and 10 of 12 patients, respectively), and diffuse aspiration
      bronchiolitis (12 patients and 12 of 13 patients, respectively). On the other
      hand, ill-defined centrilobular nodules of ground-glass attenuation were
      frequently seen in patients with subacute hypersensitivity pneumonitis (all 15
      patients), metastatic calcification (all 4 patients), Churg-Strauss syndrome (4
      of 12 patients), microscopic polyangiitis (27 of 48 patients), systemic lupus
      erythematosus (7 of 8 patients), and respiratory bronchiolitis-associated
      interstitial lung disease (all 8 patients). Pathologically, the tree-in-bud
      appearance correlated well with the plugging of small airways with mucous, pus,
      or fluid; dilated bronchioles; and bronchiolar wall thickening. Ill-defined
      centrilobular nodules represented peribronchiolar inflammation or the deposition
      of hemorrhagic materials. CONCLUSIONS: Knowledge of the two centrilobular
      patterns is of proven worth for generating differential diagnoses and is of
      particular value in suggesting a likely infectious etiology in cases with tree-in
      bud appearance.

PMID- 18079228
TI  - Lung allocation score for lung transplantation: impact on disease severity and
      survival.
AB  - BACKGROUND: Prior to implementation of the lung allocation score (LAS) system,
      allocation of donor lungs was based on accrued time on the waiting list and was
      potentially influenced by center-specific thresholds for listing. The impact of
      LAS implementation on patient characteristics and survival is unknown. METHODS:
      United Network of Organ Sharing data were obtained on all lung transplant
      candidates listed and all patients undergoing transplantation in region 6 between
      May 4, 2003, and May 4, 2006. Each data set was divided into two cohorts: 2 years
      before LAS implementation, and 1 year after LAS implementation. LAS was
      calculated and compared by cohort. Pre-LAS and post-LAS differences in patient
      characteristics were examined. Waiting list and posttransplant survival rates for
      each cohort were examined using Kaplan-Meier estimates and Cox regression.
      RESULTS: After LAS implementation, the distribution of diagnoses in patients
      undergoing transplantation significantly changed (p = 0.02), while the
      distribution of diagnoses in those listed did not (p = 0.17). Characteristics of
      patients on the waiting list were similar, except that a higher proportion of
      nonwhite patients were listed (p = 0.04) and lower FVC (p < 0.001) was observed
      after LAS implementation. Similarly, characteristics of patients undergoing
      transplantation did not change, except that posttransplant hospital length of
      stay was shorter (p = 0.01) after LAS implementation. Calculated LAS was higher
      after LAS implementation (p = 0.006). After controlling for age and diagnosis,
      neither waiting list nor transplant survival was significantly different (p =
      0.93 and p = 0.81, respectively). CONCLUSIONS: After LAS implementation, the
      distribution of diagnoses in lung transplant recipients was significantly
      changed, while that of candidates was not. Posttransplant and waiting list
      survival were not affected by the LAS system, but power was limited. Larger and
      long-term survival studies are needed to determine if the LAS system improves
      overall allocation and survival for patients interested in lung transplantation.

PMID- 18079229
TI  - Asthma and atypical bacterial infection.
AB  - A growing body of basic and clinical science implicates the atypical bacterial
      pathogens Mycoplasma pneumoniae and Chlamydophila (formerly Chlamydia) pneumoniae
      as potentially important factors in asthma, although their exact contribution to
      asthma development and/or persistence remains to be determined. Evidence from
      human studies links both M pneumoniae and C pneumoniae to new-onset wheezing,
      exacerbations of prevalent asthma, and long-term decrements in lung function,
      suggesting that these organisms can play an important role in the natural history
      of asthma. Furthermore, animal models of acute and chronic infection with these
      organisms indicate that they have the ability to modulate allergic sensitization
      and pulmonary physiologic and immune response to allergen challenge. These
      findings raise the possibility that, in at least some individuals with asthma,
      antibiotic therapy might have a role in long-term treatment. While antibiotics do
      not currently have a defined role in the treatment of stable patients with
      chronic asthma, there is emerging evidence that asthma symptoms and biomarkers of
      airway inflammation can improve when patients who have atypical bacterial
      infection as a cofactor in their asthma are treated with macrolide antibiotics.
      Ongoing research into the importance of atypical pathogens in asthma will further
      elucidate whether these infections are important in disease development or
      whether their prevalence is increased in asthmatic subjects due to chronic airway
      inflammation or other, yet unidentified, predisposing factors. Current studies
      will further define the role of macrolide antibiotics in the treatment of stable
      patients with asthma, ultimately determining whether these therapeutic agents
      have a place in asthma management.

PMID- 18079230
TI  - Recent developments in the diagnosis and management of severe sepsis.
AB  - The last 5 years have brought dramatic changes to the care of patients with
      severe sepsis. While early diagnosis remains a challenge and, regrettably, a
      rapid, sensitive, and specific diagnostic test is still lacking, the methods to
      identify those critically ill patients who are likely to die have become clearer.
      The presence of multiple organ failure, vasopressor-dependent shock, and high
      values in formalized scoring methods such as the APACHE (acute physiology and
      chronic health evaluation) and sequential organ failure assessment systems all
      have some utility for outcome prediction for groups of patients. Refinements in
      long-used supportive practices such as lower tidal volume ventilation and
      enhanced glucose control have improved outcomes. A growing appreciation of the
      importance of timely provision of antimicrobial therapy, circulatory
      resuscitation, and activated protein C administration have also improved
      survival. Optimal treatment candidates for, and the timing and dose of some
      treatments (eg, corticosteroids) remain controversial and are undergoing
      additional study. Perhaps the most important change in the care of patients with
      severe sepsis is awareness that the syndrome is more common, lethal, and
      expensive, than previously appreciated, and as such it warrants an organized
      approach to care provided by experts. Although there is still much to learn,
      numerous studies now indicate that improvements in outcomes are possible when
      treatment protocols that incorporate all known beneficial therapies are applied
      in a timely fashion.

PMID- 18079231
TI  - American College of Chest Physicians consensus statement on the respiratory and
      related management of patients with Duchenne muscular dystrophy undergoing
      anesthesia or sedation.
AB  - This statement on the management of patients with Duchenne muscular dystrophy
      (DMD) undergoing procedural sedation or general anesthesia represents the
      consensus opinion of a multidisciplinary panel convened under the auspices of the
      American College of Chest Physicians. Expert recommendations on this subject are
      needed for several reasons. First, patients with DMD have an increased risk of
      complications when they undergo sedation or general anesthesia. In addition, due
      to improved cardiopulmonary therapies, patients with DMD are experiencing an
      unprecedented duration of survival. As a result, it is more common for them to
      require procedures involving sedation or general anesthesia. The risks related to
      anesthesia and sedation for DMD patients include potentially fatal reactions to
      inhaled anesthetics and certain muscle relaxants, upper airway obstruction,
      hypoventilation, atelectasis, congestive heart failure, cardiac dysrhythmias,
      respiratory failure, and difficulty weaning from mechanical ventilation. This
      statement includes advice regarding the highly interrelated areas of respiratory,
      cardiac, GI, and anesthetic management of patients with DMD undergoing general
      anesthesia or procedural sedation. The statement is intended to aid clinicians
      involved in the care of patients with DMD and to be a resource for other
      stakeholders in this field, including patients and their families. It is an up-to
      date summary of medical literature regarding this topic and identifies areas in
      need of future research.

PMID- 18079232
TI  - Futility: a concept in evolution.
AB  - The debate about how to resolve cases in which patients and families demand
      interventions that clinicians regard as futile has been in evolution over the
      past 20 years. This debate can be divided into three generations. The first
      generation was characterized by attempts to define futility in terms of certain
      clinical criteria. These attempts failed because they proposed limitations to
      care based on value judgments for which there is no consensus among a significant
      segment of society. The second generation was a procedural approach that
      empowered hospitals, through their ethics committees, to decide whether
      interventions demanded by families were futile. Many hospitals adopted such
      policies, and some states incorporated this approach into legislation. This
      approach has also failed because it gives hospitals authority to decide whether
      or not to accede to demands that the clinicians regard as unreasonable, when any
      national consensus on what is a "beneficial treatment" remains under intense
      debate. Absent such a consensus, procedural mechanisms to resolve futility
      disputes inevitably confront the same insurmountable barriers as attempts to
      define futility. We therefore predict emergence of a third generation, focused on
      communication and negotiation at the bedside. We present a paradigm that has
      proven successful in business and law. In the small number of cases in which even
      the best efforts at communication and negotiation fail, we suggest that
      clinicians should find ways to better support each other in providing this care,
      rather than seeking to override the requests of these patients and families.

PMID- 18079233
TI  - Noninvasive estimation of the lactate threshold in a subject with dissociated
      ventilatory and pulmonary gas exchange indices: a case report.
AB  - This case report describes the responses to incremental work-rate exercise in a
      healthy subject (with normal pulmonary function), for whom the pulmonary gas
      exchange (V-slope) and ventilatory-related indexes (ie, ventilatory equivalents
      and end-tidal partial pressures for O2 and CO2) uncharacteristically do not occur
      at the same metabolic rate. Based on the results of additional constant-work-rate
      exercise tests, we propose that in the (occasional) event of such a dissociation
      between the V-slope and ventilatory-related responses normally associated with
      the lactate threshold (theta L), then the V-slope index should take priority as
      the theta L estimator.

PMID- 18079235
TI  - Developing a cardiopulmonary exercise testing laboratory.
AB  - BACKGROUND: Cardiopulmonary exercise testing is a noninvasive and cost-effective
      technique that adds significant value to the assessment and management of a
      variety of symptoms and diseases. The penetration of this testing in medical
      practice may be limited by perceived operational and financial barriers.
      PROCEDURE: This article reviews coding and supervision requirements related to
      both simple and complex pulmonary stress testing. A program evaluation and review
      technique diagram is used to describe the work flow process. Data from our
      laboratory are used to generate an income statement that separates fixed and
      variable costs and calculates the contribution margin. A cost-volume-profit
      (break-even) analysis is then performed. RESULTS: Using data from our laboratory
      including fixed and variable costs, payer mix, reimbursements by payer, and the
      assumption that the studies are divided evenly between simple and complex
      pulmonary stress tests, the break-even number is calculated to be 300 tests per
      year. A calculator with embedded formulas has been designed by the author and is
      available on request. CONCLUSIONS: Developing a cardiopulmonary exercise
      laboratory is challenging but achievable and potentially profitable. It should be
      considered by a practice that seeks to distinguish itself as a quality leader.
      Providing this clinically valuable service may yield indirect benefits such as
      increased patient volume and increased utilization of other services provided by
      the practice. The decision for a medical practice to commit resources to
      managerial accounting support requires a cost-benefit analysis, but may be a
      worthwhile investment in our challenging economic environment.

PMID- 18079234
TI  - Cryptogenic organizing pneumonitis during oxaliplatin chemotherapy for colorectal
      cancer: case report.
AB  - The patient presented here is a 30-year-old woman who underwent anterior
      resection for the initial treatment of rectal cancer. A postoperative study
      showed a single liver metastasis. The patient received adjuvant pelvic
      radiotherapy with concomitant 5-fluorouracil (5-FU) treatment followed by liver
      metastasectomy 6 weeks after the completion of radiation therapy and
      chemotherapy. Adjuvant therapy with 5-FU, leucovorin, and oxaliplatin (FOLFOX 4
      regimen) was continued. The initial five cycles were well tolerated with the
      occurrence of only paresthesia that did not interfere with function. After the
      sixth cycle of the treatment, progressive dyspnea and persistent cough developed
      in the patient, although her clinical history was negative for lung disease. A
      chest radiograph revealed diffuse bilateral interstitial infiltrates, and a chest
      CT scan showed bilateral alveolar infiltrates predominant in the right lung. Lung
      biopsy by video-assisted thoracoscopy was performed, and the histologic report
      showed cryptogenic organizing pneumonitis (COP). Prednisone therapy (1 mg/kg/d)
      resulted in a very good clinical response. In fact, the patient had complete
      remission of respiratory symptoms including cough and dyspnea after 4 days of
      treatment, and the chest CT scan showed complete resolution of lung infiltrates
      after 4 weeks. One month later, the patient continued adjuvant treatment with six
      cycles of 5-FU, leucovorin, and irinotecan (ie, the FOLFIRI regimen) without
      complications. Thus, oxiplatin was implicated as the likely cause of this drug
      induced lung toxicity, which is a very rare complication associated with platins.
      Diffuse interstitial lung disease, particularly COP, has been described following
      the administration of the cytotoxic agents bleomycin and busulfan, but a
      connection to oxaliplatin has not been reported before this case.

PMID- 18079236
TI  - A 29-year-old man with pulmonary complications of a thrombotic disorder.

PMID- 18079237
TI  - A 39-year-old man with epigastric pain, intermittent chest pain, and progressive
      dyspnea.

PMID- 18079238
TI  - Massive intravascular hemolysis and a rapidly fatal outcome.

PMID- 18079239
TI  - Hemodynamic evaluation and monitoring in the ICU.
AB  - Hemodynamic monitoring, a cornerstone in the management of the critically ill
      patient, is used to identify cardiovascular insufficiency, its probable cause,
      and response to therapy. Still it is difficult to document the efficacy of
      monitoring because no device improves outcome unless coupled to a treatment that
      improves outcome. Several clinical trials have consistently documented that
      preoptimization for high-risk surgery patients treated in the operating room and
      early (< 12 h) goal-directed resuscitation in septic patients treated in the
      emergency department reduce morbidity, mortality, and resource use (costs) when
      the end points of resuscitation were focused on surrogate measures of adequacy of
      global oxygen delivery (Do2). The closer the resuscitation is to the insult, the
      greater the benefit. When resuscitation was started after ICU admission in high
      risk surgical patients, reduced length of stay was also seen. The focus of these
      monitoring protocols is to establish a mean arterial pressure > 65 mm Hg and then
      to increase Do2 to 600 mL/min/m2 within the first few minutes to hours of
      presentation. To accomplish these goals, hemodynamic monitoring focuses more on
      measures of cardiac output and mixed venous oxygen saturation to access adequacy
      of resuscitation efforts than on filling pressures. Although these protocols
      reduce mortality and morbidity is selected high-risk patient groups, the
      widespread use of monitoring-driven treatment protocols has not yet happened,
      presumably because all studies have been single-center trials using a single,
      proprietary blood flow-monitoring device. Multicenter trials are needed of early
      goal-directed therapies for all patients presenting in shock of various
      etiologies and when the protocol and not the monitoring device is the primary
      variable.

PMID- 18079241
TI  - Responsibilities of authorship.

PMID- 18079240
TI  - Childhood obstructive sleep-disordered breathing: a clinical update and
      discussion of technological innovations and challenges.
AB  - Childhood sleep-disordered breathing (SDB) has been known to be associated with
      health and cognitive impacts for more than a century, and yet our understanding
      of this disorder is in its infancy. Neuropsychological consequences in children
      with snoring or subtle breathing disturbances not meeting the traditional
      definition of sleep apnea suggest that "benign, or primary snoring" may be
      clinically significant, and that the true prevalence of SDB might be
      underestimated. There is no standard definition of SDB in children. The
      polysomnographic technology used in many sleep laboratories may be inadequate to
      diagnose serious but subtle forms of clinically important airflow limitation. In
      the last several years, advances in digital technology as well as new
      observational studies of respiratory and arousal patterns in large populations of
      healthy children have led to alternative views of what constitutes sleep-related
      breathing and arousal abnormalities that may refine our diagnostic criteria. This
      article reviews our knowledge of childhood SDB, highlights recent advances in
      technology, and discusses diagnostic and treatment strategies that will advance
      the management of children with pediatric SDB.

PMID- 18079242
TI  - A 64-year-old woman with a history of rheumatoid arthritis and new cavitary lung
      lesions.

PMID- 18079243
TI  - Oxyhemoglobin dissociation curve clarification.

PMID- 18079244
TI  - Sarcoidosis, firefighters sarcoidosis, and World Trade Center "sarcoid-like"
      granulomatous pulmonary disease.

PMID- 18079245
TI  - Bronchiectasis in acute pneumonia ... Pseudobronchiectasis.

PMID- 18079246
TI  - Intubating ICU patients with ketamine: adverse effects that can occur.

PMID- 18079247
TI  - Nailing the evidence.

PMID- 18079248
TI  - Postobstructive pulmonary edema: a case for hydrostatic mechanisms.

PMID- 18079249
TI  - Recurrence of severe pulmonary hypertension following the removal of a lung
      allograft.

PMID- 18079250
TI  - Extranodal extension in metastatic non-small cell lung cancer.

PMID- 18079251
TI  - Timing of antibiotics and community-acquired pneumonia.

PMID- 18079252
TI  - Real-time sonography with central venous access: the role of self-training.

PMID- 18079253
TI  - Natural history of stage I lung cancer.

PMID- 18079254
TI  - Antibiotic use in acute exacerbations of chronic bronchitis.

PMID- 18079255
TI  - Time does not heal all wounds: medical luminaries, national socialism, and the
      American College of Chest Physicians.

PMID- 18079256
TI  - Freidrich Wegener: the past and present.

PMID- 18079257
TI  - On Wegener and the ACCP.

PMID- 18079258
TI  - Comments on Dr. Wegener editorial.

PMID- 18079259
TI  - Mechanics of the canine diaphragm in ascites: a CT study.
AB  - Ascites causes an increase in the elastance of the abdomen and impairs the lung
      expanding action of the diaphragm, but its overall effects on the pressure
      generating ability of the muscle remain unclear. In the present study, radiopaque
      markers were attached to muscle bundles in the midcostal region of the diaphragm
      in five dogs, and the three-dimensional locations of the markers during
      relaxation and during phrenic nerve stimulation in the presence of increasing
      amounts of ascites were determined using a computed tomographic scanner. From
      these data, accurate measurements of muscle length and quantitative estimates of
      diaphragm curvature were obtained, and the changes in transdiaphragmatic pressure
      (Pdi) were analyzed as functions of muscle length and curvature. With increasing
      ascites, the resting length of the diaphragm increased progressively. In
      addition, the amount of muscle shortening during phrenic nerve stimulation
      decreased gradually. When ascites was 100 ml/kg body wt, therefore, the muscle
      during contraction was longer, leading to a 20-25% increase in Pdi. As ascites
      increased further to 200 ml/kg, however, muscle length during contraction
      continued to increase, but Pdi did not. This absence of additional increase in
      Pdi was well explained by the increase in the diameter of the ring of insertion
      of the diaphragm to the rib cage and the concomitant increase in the radius of
      diaphragm curvature. These observations indicate that the pressure-generating
      ability of the diaphragm is determined not only by muscle length as
      conventionally thought but also by muscle shape.

PMID- 18079260
TI  - Individualized performance prediction of sleep-deprived individuals with the two
      process model.
AB  - We present a new method for developing individualized biomathematical models that
      predict performance impairment for individuals restricted to total sleep loss.
      The underlying formulation is based on the two-process model of sleep regulation,
      which has been extensively used to develop group-average models. However, in the
      proposed method, the parameters of the two-process model are systematically
      adjusted to account for an individual's uncertain initial state and unknown trait
      characteristics, resulting in individual-specific performance prediction models.
      The method establishes the initial estimates of the model parameters using a set
      of past performance observations, after which the parameters are adjusted as each
      new observation becomes available. Moreover, by transforming the nonlinear
      optimization problem of finding the best estimates of the two-process model
      parameters into a set of linear optimization problems, the proposed method yields
      unique parameter estimates. Two distinct data sets are used to evaluate the
      proposed method. Results of simulated data (with superimposed noise) show that
      the model parameters asymptotically converge to their true values and the model
      prediction accuracy improves as the number of performance observations increases
      and the amount of noise in the data decreases. Results of a laboratory study (82
      h of total sleep loss), for three sleep-loss phenotypes, suggest that
      individualized models are consistently more accurate than group-average models,
      yielding as much as a threefold reduction in prediction errors. In addition, we
      show that the two-process model of sleep regulation is capable of representing
      performance data only when the proposed individualized model is used.

PMID- 18079261
TI  - Effect of weight loss on lactate transporter expression in skeletal muscle of
      obese subjects.
AB  - The effects of weight loss on skeletal muscle lactate transporter
      [monocarboxylate transporter (MCT)] expression in obese subjects were
      investigated to better understand how lactate transporter metabolism is regulated
      in insulin-resistant states. Ten obese subjects underwent non-macronutrient
      specific energy restriction for 15 wk. Anthropometric measurements and a needle
      biopsy of the vastus lateralis muscle before and after the weight loss program
      were performed. Enzymatic activity, fiber type distribution, and skeletal muscle
      MCT protein expression were measured. Muscle from nonobese control subjects was
      used for comparison of MCT levels. The program induced a weight loss of 9.2 +/-
      1.6 kg. Compared with controls, muscle from obese subjects showed a strong
      tendency (P = 0.06) for elevated MCT4 expression (+69%) before the weight loss
      program. MCT4 expression decreased (-7%) following weight loss to reach levels
      that were not statistically different from control levels. There were no
      differences in MCT1 expression between controls and obese subjects before and
      after weight loss. A highly predictive regression model (R2 = 0.93), including
      waist circumference, citrate synthase activity, and percentage of type 1 fibers,
      was found to explain the highly variable MCT1 response to weight loss in the
      obese group. Therefore, in obesity, MCT1 expression appears linked both to
      changes in oxidative parameters and to changes in visceral adipose tissue
      content. The strong tendency for elevated expression of muscle MCT4 could reflect
      the need to release greater amounts of muscle lactate in the obese state, a
      situation that would be normalized with weight loss as indicated by decreased
      MCT4 levels.

PMID- 18079262
TI  - Diurnal variation, response to eccentric exercise, and association of
      inflammatory mediators with muscle damage variables.
AB  - This investigation determined whether inflammatory mediators 1) have diurnal
      variations, 2) respond to high-force eccentric exercise, and 3) associate with
      markers of muscle damage after high-force eccentric exercise. College-aged men
      and women (n = 51) completed exercise (3 x 15 maximal eccentric elbow flexor
      actions using 1 arm) and control conditions in random order. Blood was collected
      preexercise and 4, 8, 12, 24, 48, and 96 h postexercise. Additional measures
      included maximal isometric force and midbiceps arm circumference (to detect
      swelling). Serum and plasma were analyzed for soluble tumor necrosis factor
      receptor-1 (sTNFR1), IL-6, C-reactive protein, cortisol, and creatine kinase (CK)
      activity. Relative to the 7:00 AM point in the control condition, diurnal
      decreases were measured at 12:00 PM and 4:00 PM for IL-6 and at 12:00 PM, 4:00
      PM, and 8:00 PM for sTNFR1 and cortisol. sTNFR1, IL-6, CK, swelling, and soreness
      were higher in the exercise compared with the control condition. The largest of
      the inflammatory mediator responses was measured for IL-6 8 h postexercise in the
      exercise (3.00 +/- 3.59 pg/ml) relative to the control condition (1.15 +/- 0.99
      pg/ml). The IL-6 response (time-matched exercise--control concentration) at 8 h
      associated (r > 0.282) with muscle soreness at 24 and 96 h, and the cortisol
      response at 8 h associated (r > 0.285) with swelling at 8, 24, and 96 h. Thus
      soreness and swelling, but not CK and strength loss, had a low association with
      the inflammatory response following eccentric exercise.

PMID- 18079263
TI  - Wave reflection and central aortic pressure are increased in response to static
      and dynamic muscle contraction at comparable workloads.
AB  - We determined the effects of static and dynamic muscle contraction at equivalent
      workloads on central aortic pressure and wave reflection. At random, 14 healthy
      men and women (23 +/- 5 yr of age) performed a static handgrip forearm
      contraction [90 s at 30% of maximal voluntary contraction (MVC)], dynamic
      handgrip contractions (1 contraction/s for 180 s at 30% MVC), and a control
      trial. During static and dynamic trials, tension-time index was controlled by
      holding peak tension constant. Measurements of brachial artery blood pressure and
      the synthesis of a central aortic pressure waveform (by radial artery applanation
      tonometry and generalized transfer function) were conducted at baseline, during
      each trial, and during 1 min of postexercise ischemia (PEI). Aortic augmentation
      index (AI), an index of wave reflection, was calculated from the aortic pressure
      waveform. AI increased during both static and dynamic trials (static, 5.2 +/- 3.1
      to 11.8 +/- 3.4%; dynamic, 5.8 +/- 3.0 to 13.3 +/- 3.4%; P < 0.05) and further
      increased during PEI (static, 18.5 +/- 3.1%; dynamic, 18.6 +/- 2.9%; P < 0.05).
      Peripheral and central systolic and diastolic pressures increased (P < 0.05)
      during both static and dynamic trials and remained elevated during PEI. AI and
      pressure responses did not differ between static and dynamic trials. Peripheral
      and central pressures increased similarly during static and dynamic contraction;
      however, the rise in central systolic pressure during both conditions was
      augmented by increased wave reflection. The present data suggest that wave
      reflection is an important determinant of the central blood pressure response
      during forearm muscle contractions.

PMID- 18079264
TI  - Can exercise modulate the maturation of functionally different immature tendons
      in the horse?
AB  - Tendons can be considered in two functional groups, those contributing to
      energetics of locomotion and those acting solely to position the limb. The energy
      storing tendons in both human and equine athletes have a high frequency of injury
      with similar pathophysiology. In previous studies, high-intensity exercise
      appears to induce a disruption of the matrix rather than functional adaptation in
      adults. Here we explore the hypothesis that the introduction of controlled
      exercise during growth would result in an adaptive response without deleterious
      effects. Young horses were given a controlled exercise program similar to that
      previously shown to induce matrix changes in energy-storing tendons of skeletally
      mature animals. The tendons were assessed in relation to mechanical properties,
      molecular composition, and morphology. Results showed a significant increase in
      cartilage oligomeric matrix protein (COMP) in the positional tendon but not in
      the energy-storing tendon. Other matrix properties and mechanical properties were
      not significantly changed. While the imposition of high-strain-rate exercise in
      immature horses failed to augment the development of the energy-storing tendon
      over and above that induced by normal pasture exercise, it did not induce
      deleterious changes, supporting an earlier introduction of athletic training in
      horses.

PMID- 18079265
TI  - High specific torque is related to lengthening contraction-induced skeletal
      muscle injury.
AB  - Animal models implicate multiple mechanical factors in the initiation of exercise
      induced muscle injury. Muscle injury has been widely studied in humans, but few
      data exist regarding the underlying cause of muscle injury. This study sought to
      examine the role of torque per active muscle volume in muscle injury. Eight
      subjects performed 80 electrically stimulated [via electromyostimulation (EMS)]
      eccentric contractions of the right and left quadriceps femoris (QF) through an
      80 degrees arc at 120 degrees /s. Specific torque was varied by applying 25-Hz
      EMS to one thigh and 100-Hz EMS to the contralateral thigh. Transverse relaxation
      time (T2) magnetic resonance images of the QF were collected before and 3 days
      after the eccentric exercise bouts. Injury was assessed via changes in isometric
      force and ratings of soreness over the course of 14 days after exercise and by
      determining changes in T2 and muscle volume 3 days after exercise. The 100-Hz EMS
      induced greater force loss (P < 0. 05), soreness (P < 0.05), change in muscle
      volume (P = 0.03), and volume of muscle demonstrating increased T2 (P = 0.005)
      than the 25-Hz EMS. In addition, injury was found to be similar across the QF in
      all but the most proximal regions of the QF. Our findings suggest that, in
      humans, high torque per active volume during lengthening muscle contractions is
      related to muscle injury.

PMID- 18079266
TI  - Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle
      lipid peroxidation in the OLETF rat.
AB  - The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a model of hyperphagic
      obesity in which the animals retain the desire to run voluntarily. Running wheels
      were provided for 4-wk-old OLETF rats for 16 wk before they were killed 5 h
      (WL5), 53 h (WL53), or 173 h (WL173) after the wheels were locked. Sedentary
      (SED) OLETF rats that were not given access to running wheels served as age
      matched cohorts. Epididymal fat pad mass, adipocyte volume, and adipocyte number
      were 58%, 39%, and 47% less, respectively, in WL5 than SED rats. Contrary to
      cessation of daily running in Fischer 344 x Brown Norway rats, epididymal fat did
      not increase during the first 173 h of running cessation in the OLETF runners.
      Serum insulin and glucose levels were 77% and 29% less, respectively, in WL5 than
      SED rats. Oil red O staining for intramyocellular lipid accumulation was not
      statistically different among groups. However, lipid peroxidation levels, as
      determined by total trans-4-hydroxy-2-nonenal (4-HNE) and 4-HNE normalized to oil
      red O, was higher in epitrochlearis muscles of SED than WL5, WL53, and WL173
      rats. mRNA levels of glutathione S-transferase-alpha type 4, an enzyme involved
      in cellular defense against electrophilic compounds such as 4-HNE, were higher in
      epitrochlearis muscle of WL53 than WL173 and SED rats. In contrast, 4-HNE levels
      in omental fat were unaltered. Epitrochlearis muscle palmitate oxidation and
      relative transcript levels for peroxisome proliferator-activated receptor-delta
      and peroxisome proliferator-activated receptor-gamma coactivator type 1 were
      surprisingly not different between runners and SED rats. In summary, voluntary
      running was associated with lower levels of lipid peroxidation in skeletal muscle
      without significant changes in intramyocellular lipids or mitochondrial markers
      in OLETF rats at 20 wk of age. Therefore, even in a genetic animal model of
      extreme overeating, daily physical activity promotes improved health of skeletal
      muscle.

PMID- 18079267
TI  - Modulation of spontaneous baroreflex control of heart rate and indexes of vagal
      tone by passive calf muscle stretch during graded metaboreflex activation in
      humans.
AB  - We examined whether spontaneous baroreflex modulation of heart rate and other
      indexes of cardiac vagal tone could be altered by passive stretch of the human
      calf muscle during graded concurrent activation of the muscle metaboreflex. Ten
      healthy subjects performed four trials: a control trial, resting for 1.5 min (0%
      trial); or 1.5 min of one-legged isometric plantar flexor exercise at 30, 50, and
      70% maximal voluntary contraction. The incremental increases in blood pressure
      (BP) caused were then partially sustained by subsequent local circulatory
      occlusion (CO). After 3.5 min of CO alone, sustained calf stretch and CO were
      applied for 3 min. Spontaneous baroreflex sensitivity (SBRS) was progressively
      decreased with increasing exercise intensity (P < 0.05). During CO, stretch
      decreased SBRS and increased BP similarly in all trials (P < 0.05). Within 15 s
      of stretch onset, heart rate (HR) increased by 6 +/- 1, 6 +/- 1, 8 +/- 1, and 6
      +/- 2 beats/min in the 0, 30, 50, and 70% trials, respectively (P < 0.05), and
      root mean square of successive differences was decreased from CO-alone levels (P
      < 0.05). During the second and third minutes of stretch, HR fell back but
      remained significantly above CO levels, and common coefficient of variance of R-R
      interval decreased progressively with increasing prior exercise intensity (P <
      0.05; 70% trial). This suggests that passive stretch of the human calf muscles
      decreases cardiac vagal outflow irrespective of the levels of BP increase caused
      by muscle metaboreflex activation and implies that central modulation of
      baroreceptor input, mediated by the actions of stretch-activated mechanoreceptive
      muscle afferent fibers, continues.

PMID- 18079269
TI  - Thermoregulation during exercise in the heat in children: old concepts revisited.
AB  - Children possess certain physiological and anatomic characteristics that have
      traditionally been considered to impair thermoregulatory responses to exercise in
      the heat: low exercise economy, high ratio of body surface area to mass,
      diminished sweating capacity, and less cardiac output at the same work load
      compared with adults. Consequently, children have been regarded as an at-risk
      group for not only decrements of physical performance but also heat injury during
      physical activities performed in conditions of high ambient temperature. Recent
      investigations that have directly compared thermoregulatory responses to exercise
      in the heat in children and adults have challenged these traditional concepts.
      Such studies have failed to indicate group differences in heat dispersal when
      adult-child comparisons are appropriately considered in respect to relative
      exercise intensity. These findings imply that no maturational differences exist
      in thermal balance or endurance performance during exercise in the heat, nor that
      child athletes are more vulnerable to heat injury.

PMID- 18079268
TI  - Exercise training enhances baroreflex sensitivity by an angiotensin II-dependent
      mechanism in chronic heart failure.
AB  - Exercise training (EX) has become an important modality capable of enhancing the
      quality of life and survival of patients with chronic heart failure (CHF).
      Although 4 wk of EX in animals with CHF evoked a reduction in renal sympathetic
      nerve activity and ANG II plasma levels and an enhancement in baroreflex
      sensitivity at rest (Liu JL, Irvine S, Reid IA, Patel KP, Zucker IH, Circulation
      102: 1854-1862, 2000; Liu JL, Kulakofsky J, Zucker IH, J Appl Physiol 92: 2403
      2408, 2002), it is unclear whether these phenomena are causally related. CHF was
      induced in rabbits by ventricular pacing (360-380 beats/min) for 3 wk. CHF
      rabbits were EX for 4 wk at 15-18 m/min, 6 days/wk, 30-40 min/day. Three groups
      of rabbits were studied: CHF (with no EX), CHF-EX, and CHF-EX + ANG II infusion
      [in which ANG II levels were kept at or near levels observed in CHF (non-EX)
      rabbits by subcutaneous osmotic minipump infusion]. EX prevented the increase in
      plasma ANG II levels shown in CHF rabbits. CHF and CHF-EX + ANG II infusion
      rabbits had significantly depressed baroreflex sensitivity slopes (P < 0.01 for
      sodium nitroprusside and P < 0.001 for phenylephrine) and higher baseline renal
      sympathetic nerve activities than CHF-EX animals. EX downregulated mRNA and
      protein expression of ANG II type 1 receptors in the rostral ventrolateral
      medulla in CHF rabbits. This was prevented by ANG II infusion. These data are
      consistent with the view that the reduction in sympathetic nerve activity and the
      improvement in baroreflex function in CHF after EX are due to the concomitant
      reduction in ANG II and angiotensin receptors in the central nervous system.

PMID- 18079270
TI  - Influence of tongue muscle contraction and dynamic airway pressure on
      velopharyngeal volume in the rat.
AB  - The mammalian pharynx is a collapsible tube that narrows during inspiration as
      transmural pressure becomes negative. The velopharynx (VP), which lies posterior
      to the soft palate, is considered to be one of the most collapsible pharyngeal
      regions. I tested the hypothesis that negative transmural pressure would narrow
      the VP, and that electrical stimulation of extrinsic tongue muscles would reverse
      this effect. Pressure (-6, -3, 3, and 6 cmH2O) was applied to the isolated
      pharyngeal airway of anesthetized rats that were positioned in a 4.7-T MRI
      scanner. The volume of eight axial slices encompassing the length of the VP was
      computed at each level of pressure, with and without bilateral hypoglossal nerve
      stimulation (0.1-ms pulse, one-third maximum force, 80 Hz). Negative pressure
      narrowed the VP, and either whole hypoglossal nerve stimulation (coactivation of
      protrudor and retractor muscles) or medial nerve branch stimulation (independent
      activation of tongue protrudor muscles) reversed this effect, with the greatest
      impact in the caudal one-third of the VP. The dilating effects of medial branch
      stimulation were slightly larger than whole nerve stimulation. Positive pressure
      dilated the VP, but tongue muscle contraction did not cause further dilation
      under these conditions. I conclude that the narrowest and most collapsible
      segment of the rat pharynx is in the caudal VP, posterior to the tip of the soft
      palate. Either coactivation of protrudor and retractor muscles or independent
      contraction of protrudor muscles caused dilation of this region, but the latter
      was slightly more effective.

PMID- 18079272
TI  - Prostaglandin synthesis can be inhibited locally by infusion of NSAIDS through
      microdialysis catheters in human skeletal muscle.
AB  - Prostaglandins are known to be involved in the regulation of local blood flow
      within human skeletal muscles during exercise, and the concentration of
      prostaglandins increases locally and systemically in response to exercise. The
      systemic release of prostaglandins can be inhibited by oral intake of
      nonsteroidal anti-inflammatory drugs (NSAIDs). However, to study the local role
      of prostaglandins, the formation of prostaglandins within the tissue must be
      controlled. Microdialysis enables determination of local concentrations of water
      soluble substances within the tissue. In the present study, the microdialysis
      method was used to infuse NSAIDs locally into human skeletal muscles producing a
      local block of prostaglandin formation. In addition, the graded blockade at
      various distances from the infusion site within the muscle during rest, exercise
      and recovery was determined. Microdialysis was performed in thigh muscles (vastus
      lateralis muscle) in six healthy men. One of the microdialysis catheters was used
      to block prostaglandin synthesis by infusion of the NSAID indomethacin.
      Additional catheters were placed 1 and 4 cm away from the infusion and in the
      contralateral leg (working control). Following 2 h of rest, the subjects
      performed 200 maximal eccentric contractions with each leg followed by 3 h of
      rest. The study revealed that infusion of NSAID reduced local prostaglandin E(2)
      concentration by approximately 30-50% (4 cm away from the infusion) and 85% (1 cm
      away from the infusion) compared with the contralateral (unblocked) thigh muscle.
      In conclusion, the present study shows that infusion of NSAIDs into human muscle
      via microdialysis catheters results in a graded blockade of prostaglandin
      synthesis.

PMID- 18079271
TI  - Femoral-gluteal subcutaneous and intermuscular adipose tissues have independent
      and opposing relationships with CVD risk.
AB  - Femoral-gluteal adipose tissue (AT) may be cardioprotective through fatty acids
      uptake. Femoral-gluteal AT has previously been defined as leg fat measured by
      dual energy x-ray absorptiometry (DXA); however, subcutaneous adipose tissue
      (SAT) and intermuscular adipose tissue (IMAT) are inseparable using DXA. This
      study investigated the independent relationships between femoral-gluteal SAT,
      femoral-gluteal IMAT, and cardiovascular disease (CVD) risk factors [fasting
      serum measures of glucose, total cholesterol (TC), high density lipoprotein
      cholesterol (HDLC), triglycerides (TG) and insulin] and whether race differences
      exist in femoral-gluteal AT distribution. Adult Caucasians (56 men and 104
      women), African-Americans (37 men and 76 women), and Asians (11 men and 35 women)
      had total AT (TAT) including femoral-gluteal AT (upper leg SAT and IMAT) and
      visceral AT (VAT) by magnetic resonance imaging (MRI). General linear models
      identified the independent effects of femoral-gluteal SAT and femoral-gluteal
      IMAT on each risk factor after covarying for TAT, VAT, age, race, sex, and two
      way interactions. Femoral-gluteal IMAT and glucose (P < 0.05) were positively
      associated independent of VAT. There were also significant inverse associations
      between femoral-gluteal SAT and insulin (P < 0.01) and TG (P < 0.05), although
      the addition of VAT rendered these effects nonsignificant, possibly due to
      collinearity. Asian women had less femoral-gluteal SAT and greater VAT than
      Caucasians and African-Americans (P < 0.05) and Asian and African-American men
      had greater femoral-gluteal IMAT than Caucasians, adjusted for age and TAT (P <
      0.05 for both). Femoral-gluteal SAT and femoral-gluteal IMAT distribution varies
      by sex and race, and these two components have independent and opposing
      relationships with CVD risk factors.

PMID- 18079273
TI  - Long-term cardiovascular effects of neonatal dexamethasone treatment: hemodynamic
      follow-up by left ventricular pressure-volume loops in rats.
AB  - Dexamethasone is clinically applied in preterm infants to treat or prevent
      chronic lung disease. However, concern has emerged about adverse side effects.
      The cardiovascular short-term side effects of neonatal dexamethasone treatment
      are well documented, but long-term consequences are unknown. Previous studies
      showed suppressed mitosis during dexamethasone treatment, leading to reduced
      ventricular weight, depressed systolic function, and compensatory dilatation in
      prepubertal rats. In addition, recent data indicated a reduced life expectancy.
      Therefore, we investigated the long-term effects of neonatal dexamethasone
      treatment on cardiovascular function. Neonatal rats were treated with
      dexamethasone or received saline. Cardiac function was determined in 8-, 50-, and
      80-wk-old animals, representing young adult, middle-aged, and elderly stages. A
      pressure-conductance catheter was introduced into the left ventricle to measure
      pressure-volume loops. Subsequently, the hearts were collected for histological
      examination. Our results showed reduced ventricular and body weights in
      dexamethasone-treated rats at 8 and 80 wk, but not at 50 wk. Cardiac output and
      diastolic function were unchanged, but systolic function was depressed at 50 and
      80 wk, evidenced by reduced ejection fractions and rightward shifts of the end
      systolic pressure-volume relationships. We concluded that previously demonstrated
      early adverse effects of neonatal dexamethasone treatment are transient but that
      reduced ventricular weight and systolic dysfunction become manifest again in
      elderly rats. Presumably, cellular hypertrophy initially compensates for the
      dexamethasone treatment-induced lower number of cardiomyocytes, but this
      mechanism falls short at a later stage, leading to systolic dysfunction. If
      applicable to humans, cardiac screening of a relatively large patient group to
      enable secondary prevention may be indicated.

PMID- 18079274
TI  - The two isoforms of the Na+/Ca2+ exchanger, NCX1 and NCX3, constitute novel
      additional targets for the prosurvival action of Akt/protein kinase B pathway.
AB  - The proteins NCX1, NCX2, and NCX3 expressed on the plasma membrane of neurons
      play a crucial role in ionic regulation because they are the major bidirectional
      system promoting the efflux and influx of Na(+) and Ca(2+) ions. Here, we
      demonstrate that NCX1 and NCX3 proteins are novel additional targets for the
      survival action of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Indeed,
      the doxycycline-dependent overexpression of constitutively active Akt1 in
      tetracycline (Tet)-Off PC-12 positive mutants and the exposure of Tet-Off PC-12
      wild type to nerve growth factor induced an up-regulation of NCX1 and NCX3
      proteins. NCX1 up-regulation induced by Akt1 activation occurred at the
      transcriptional level because NCX1 mRNA increased, and it was counteracted by
      cAMP response element-binding protein 1 inhibition through small interfering RNA
      strategy. In contrast, Akt1-induced NCX3 up-regulation recognized a post
      transcriptional mechanism occurring at the proteasome level because 1) NCX3
      transcript did not increase and 2) the proteasome inhibitor N-benzyloxycarbonyl
      (Z)-Leu-Leu-leucinal (MG-132) did not further enhance NCX3 protein levels in Akt1
      active mutants as it would be expected if the ubiquitin-proteasome complex was
      not already blocked by Akt1 pathway. As expected, in PC-12 Tet-Off wild-type
      cells MG-132 enhanced NCX3 protein levels. This up-regulation produced an
      increased activity of NCX function. Furthermore, NCX1 and NCX3 up-regulation
      contributed to the survival action of Akt1 during chemical hypoxia because both
      the silencing of NCX1 or NCX3 and the pharmacological paninhibition of NCX
      isoforms reduced the prosurvival property of Akt1. Together, these results
      indicated that NCX1 and NCX3 represent novel additional molecular targets for the
      prosurvival action of PI3-K/Akt pathway.

PMID- 18079275
TI  - Atomic force microscopy reveals the stoichiometry and subunit arrangement of the
      alpha4beta3delta GABA(A) receptor.
AB  - The GABA(A) receptor is a chloride-selective ligand-gated ion channel of the Cys
      loop superfamily. The receptor consists of five subunits arranged
      pseudosymmetrically around a central pore. The predominant form of the receptor
      in the brain contains alpha(1)-, beta(2)-, and gamma(2)-subunits in the
      arrangement alphabetaalphagammabeta, counter-clockwise around the pore. GABA(A)
      receptors containing delta-instead of gamma-subunits, although a minor component
      of the total receptor population, have interesting properties, such as an
      extrasynaptic location, high sensitivity to GABA, and potential association with
      conditions such as epilepsy. They are therefore attractive targets for drug
      development. Here we addressed the subunit arrangement within the
      alpha(4)beta(3)delta form of the receptor. Different epitope tags were engineered
      onto the three subunits, and complexes between receptors and anti-epitope
      antibodies were imaged by atomic force microscopy. Determination of the numbers
      of receptors doubly decorated by each of the three antibodies revealed a subunit
      stoichiometry of 2alpha:2beta:1delta. The distributions of angles between pairs
      of antibodies against the alpha- and beta-subunits both had peaks at around 144
      degrees , indicating that these pairs of subunits were nonadjacent. Decoration of
      the receptor with ligands that bind to the extracellular domain (i.e., the lectin
      concanavalin A and an antibody that recognizes the beta-subunit N-terminal
      sequence) showed that the receptor preferentially binds to the mica extracellular
      face down. Given this orientation, the geometry of complexes of receptors with
      both an antibody against the delta-subunit and Fab fragments against the alpha
      subunits indicates a predominant subunit arrangement of alphabetaalphadeltabeta,
      counter-clockwise around the pore when viewed from the extracellular space.

PMID- 18079276
TI  - The breast cancer resistance protein (Bcrp1/Abcg2) limits fetal distribution of
      glyburide in the pregnant mouse: an Obstetric-Fetal Pharmacology Research Unit
      Network and University of Washington Specialized Center of Research Study.
AB  - Breast cancer resistance protein (BCRP) is most abundantly expressed in the
      apical membrane of placental syncytiotrophoblasts, suggesting that it may protect
      the fetus by impeding drug penetration across the placental barrier. Glyburide
      (GLB) is an antidiabetic drug routinely used to treat gestational diabetes. In
      this study, we first determined whether GLB is a BCRP/Bcrp1 substrate. The
      intracellular [(3)H]GLB concentrations in Madin-Darby canine kidney (MDCK)/BCRP
      cells were significantly lower than those in MDCK/vector cells. The addition of
      10 muM fumitremorgin C, a specific BCRP inhibitor, significantly increased the
      intracellular [(3)H]GLB concentrations approximately 2-fold in MDCK/BCRP cells,
      but it had no effect in MDCK/vector cells. Similar results were obtained using
      MDCKII parent and MDCKII/Bcrp1 cells. GLB was also shown to be a BCRP/Bcrp1
      substrate in transwell transport experiments. We then examined whether Bcrp1
      limits fetal distribution of GLB in the pregnant mouse. GLB was administered by
      retro-orbital injection to the wild-type and Bcrp1(-/-) pregnant mice. The
      maternal plasma samples and fetuses were collected at various times (0.5-240 min)
      after drug administration. The GLB concentrations in the maternal plasma samples
      and homogenates of fetal tissues were determined by high-performance liquid
      chromatography/mass spectrometry. Although the maternal plasma area under the
      concentration-time curves (AUCs) of GLB in the wild-type and Bcrp1(-/-) pregnant
      mice were comparable, the fetal AUC of GLB in the Bcrp1(-/-) pregnant mice was
      approximately 2 times greater than that in the wild-type pregnant mice. These
      results suggest that GLB is a BCRP/Bcrp1 substrate, and Bcrp1 significantly
      limits fetal distribution of GLB in the pregnant mouse, but it has only a minor
      effect on the systemic clearance of the drug.

PMID- 18079278
TI  - Inhibition of inducible nitric-oxide synthase protects human T cells from hypoxia
      induced apoptosis.
AB  - Sodium cyanide-induced chemical hypoxia triggers a series of biochemical
      alterations leading to apoptosis in many cell types, including T cells. It is
      known that chemical hypoxia promotes inducible nitric-oxide synthase (iNOS) gene
      transcription by activating its transcription factors. To determine whether iNOS
      and NO production are responsible for chemical hypoxia-induced apoptosis, we
      exposed human Jurkat T cells to sodium cyanide in the presence or absence of iNOS
      inhibitors. We found that iNOS expression is necessary for hypoxia-induced lipid
      peroxidation and leukotriene B(4) generation. The inhibition of iNOS limited T
      cell apoptosis by decreasing the activity of caspase-3 without affecting the
      expression of Fas/Apo-1/CD95 on the surface membrane of T cells. These data
      suggest iNOS-mediated NO produced endogenously in the T cell alters overall T
      cell function and results in apoptosis. Proper control of iNOS expressed in the T
      cell may represent a useful approach to immunomodulation.

PMID- 18079277
TI  - State- and use-dependent block of muscle Nav1.4 and neuronal Nav1.7 voltage-gated
      Na+ channel isoforms by ranolazine.
AB  - Ranolazine is an antianginal agent that targets a number of ion channels in the
      heart, including cardiac voltage-gated Na(+) channels. However, ranolazine block
      of muscle and neuronal Na(+) channel isoforms has not been examined. We compared
      the state- and use-dependent ranolazine block of Na(+) currents carried by muscle
      Nav1.4, cardiac Nav1.5, and neuronal Nav1.7 isoforms expressed in human embryonic
      kidney 293T cells. Resting and inactivated block of Na(+) channels by ranolazine
      were generally weak, with a 50% inhibitory concentration (IC(50)) >/= 60 microM.
      Use-dependent block of Na(+) channel isoforms by ranolazine during repetitive
      pulses (+50 mV/10 ms at 5 Hz) was strong at 100 microM, up to 77% peak current
      reduction for Nav1.4, 67% for Nav1.5, and 83% for Nav1.7. In addition, we found
      conspicuous time-dependent block of inactivation-deficient Nav1.4, Nav1.5, and
      Nav1.7 Na(+) currents by ranolazine with estimated IC(50) values of 2.4, 6.2, and
      1.7 microM, respectively. On- and off-rates of ranolazine were 8.2 microM(-1) s(
      1) and 22 s(-1), respectively, for Nav1.4 open channels and 7.1 microM(-1) s(-1)
      and 14 s(-1), respectively, for Nav1.7 counterparts. A F1579K mutation at the
      local anesthetic receptor of inactivation-deficient Nav1.4 Na(+) channels reduced
      the potency of ranolazine approximately 17-fold. We conclude that: 1) both muscle
      and neuronal Na(+) channels are as sensitive to ranolazine block as their cardiac
      counterparts; 2) at its therapeutic plasma concentrations, ranolazine interacts
      predominantly with the open but not resting or inactivated Na(+) channels; and 3)
      ranolazine block of open Na(+) channels is via the conserved local anesthetic
      receptor albeit with a relatively slow on-rate.

PMID- 18079279
TI  - Modulation of receptor phosphorylation contributes to activation of peroxisome
      proliferator activated receptor alpha by dehydroepiandrosterone and other
      peroxisome proliferators.
AB  - Dehydroepiandrosterone (DHEA), a C19 human adrenal steroid, activates peroxisome
      proliferator-activated receptor alpha (PPARalpha) in vivo but does not ligand
      activate PPARalpha in transient transfection experiments. We demonstrate that
      DHEA regulates PPARalpha action by altering both the levels and phosphorylation
      status of the receptor. Human hepatoma cells (HepG2) were transiently transfected
      with the expression plasmid encoding PPARalpha and a plasmid containing two
      copies of fatty acyl coenzyme oxidase (FACO) peroxisome-proliferator activated
      receptor responsive element consensus oligonucleotide in a luciferase reporter
      gene. Nafenopin treatment increased reporter gene activity in this system,
      whereas DHEA treatment did not. Okadaic acid significantly decreased nafenopin
      induced reporter activity in a concentration-dependent manner. Okadaic acid
      treatment of primary rat hepatocytes decreased both DHEA- and nafenopin-induced
      FACO activity in primary rat hepatocytes. DHEA induced both PPARalpha mRNA and
      protein levels, as well as PP2A message in primary rat hepatocytes. Western blot
      analysis showed that the serines at positions 12 and 21 were rapidly
      dephosphorylated upon treatment with DHEA and nafenopin. Results using specific
      protein phosphatase inhibitors suggested that protein phosphatase 2A (PP2A) is
      responsible for DHEA action, and protein phosphatase 1 might be involved in
      nafenopin induction. Mutation of serines at position 6, 12, and 21 to an
      uncharged alanine residue significantly increased transcriptional activity,
      whereas mutation to negative charged aspartate residues (mimicking receptor
      phosphorylation) decreased transcriptional activity. DHEA action involves
      induction of PPARalpha mRNA and protein levels as well as increased PPARalpha
      transcriptional activity through decreasing receptor phosphorylation at serines
      in the AF1 region.

PMID- 18079280
TI  - Dual purinergic synaptic transmission in the human enteric nervous system.
AB  - Based on findings in rodents, we sought to test the hypothesis that purinergic
      modulation of synaptic transmission occurs in the human intestine. Time series
      analysis of intraneuronal free Ca(2+) levels in submucosal plexus (SMP) from Roux
      en-Y specimens was done using Zeiss LSM laser-scanning confocal fluo-4 AM Ca(2+)
      imaging. A 3-s fiber tract stimulation (FTS) was used to elicit a synaptic Ca(2+)
      response. Short-circuit current (I(sc) = chloride secretion) was recorded in
      mucosa-SMP in flux chambers. A distension reflex or electrical field stimulation
      was used to study I(sc) responses. Ca(2+) imaging was done in 1,222 neurons
      responding to high-K(+) depolarization from 61 surgical cases. FTS evoked
      synaptic Ca(2+) responses in 62% of recorded neurons. FTS caused frequency
      dependent Ca(2+) responses (0.1-100 Hz). FTS Ca(2+) responses were inhibited by
      Omega-conotoxin (70%), hexamethonium (50%), TTX, high Mg(2+)/low Ca(2+) (< or =
      100%), or capsaicin (25%). A P2Y(1) receptor (P2Y(1)R) antagonist, MRS-2179 or
      PLC inhibitor U-73122, blocked FTS responses (75-90%). P2Y(1)R-immunoreactivity
      occurred in 39% of vasoactive intestinal peptide-positive neurons. The selective
      adenosine A(3) receptor (AdoA(3)R) agonist 2-chloro-N(6)-(3-iodobenzyl)adenosine
      5'-N-methylcarboxamide (2-Cl-IBMECA) caused concentration- and frequency
      dependent inhibition of FTS Ca(2+) responses (IC(50) = 8.5 x 10(-8) M). The
      AdoA(3)R antagonist MRS-1220 augmented such Ca(2+) responses; 2-Cl-IBMECA
      competed with MRS-1220. Knockdown of AdoA(1)R with 8-cyclopentyl-3-N-(3-{[3-(4
      fluorosulphonyl)benzoyl]-oxy}-propyl)-1-N-propyl-xanthine did not prevent 2-Cl
      IBMECA effects. MRS-1220 caused 31% augmentation of TTX-sensitive distension
      I(sc) responses. The SMP from Roux-en-Y patients is a suitable model to study
      synaptic transmission in human enteric nervous system (huENS). The
      P2Y(1)/Galphaq/PLC/inositol 1,3,5-trisphosphate/Ca(2+) signaling pathway, N-type
      Ca(2+) channels, nicotinic receptors, and extrinsic nerves contribute to
      neurotransmission in huENS. Inhibitory AdoA(3)R inhibit nucleotide or cholinergic
      transmission in the huENS.

PMID- 18079281
TI  - Prebiotic oligosaccharides and the enterohepatic circulation of bile salts in
      rats.
AB  - Human milk contains prebiotic oligosaccharides, which stimulate the growth of
      intestinal bifidobacteria and lactobacilli. It is unclear whether the prebiotic
      capacity of human milk contributes to the larger bile salt pool size and the more
      efficient fat absorption in infants fed human milk compared with formula. We
      determined the effect of prebiotic oligosaccharides on bile salt metabolism in
      rats. Rats were fed a control diet or an isocaloric diet containing a mixture of
      galactooligosaccharides (GOS), long-chain fructooligosaccharides (lcFOS), and
      acidified oligosaccharides (AOS) for 3 wk. We determined synthesis rate, pool
      size, and fractional turnover rate (FTR) of the primary bile salt cholate by
      using stable isotope dilution methodology. We quantified bile flow and biliary
      bile salt secretion rates through bile cannulation. Prebiotic intervention
      resulted in significant changes in fecal and colonic flora: the proportion of
      lactobacilli increased 344% (P < 0.01) in colon content and 139% (P < 0.01) in
      feces compared with the control group. The number of bifidobacteria also
      increased 366% (P < 0.01) in colon content and 282% in feces after the prebiotic
      treatment. Furthermore, pH in both colon and feces decreased significantly with
      1.0 and 0.5 pH point, respectively. However, despite this alteration of
      intestinal bacterial flora, no significant effect on relevant parameters of bile
      salt metabolism and cholate kinetics was found. The present data in rats do not
      support the hypothesis that prebiotics naturally present in human milk contribute
      to a larger bile salt pool size or altered bile salt pool kinetics.

PMID- 18079282
TI  - Long-term outcome, growth and digestive function in children 2 to 18 years after
      intestinal transplantation.
AB  - OBJECTIVE: Small bowel (SB) transplantation (Tx), long considered a rescue
      therapy for patients with intestinal failure, is now a well recognised
      alternative treatment strategy to parental nutrition (PN). In this retrospective
      study, we analysed graft functions in 31 children after SBTx with a follow-up of
      2-18 years (median 7 years). PATIENTS: Twelve children had isolated SBTx, 19 had
      combined liver-SBTx and 17 received an additional colon graft. Growth,
      nutritional markers, stool balance studies, endoscopy and graft histology were
      recorded every 2-3 years post-Tx. RESULTS: All children were weaned from PN after
      Tx and 26 children remained PN-free. Enteral nutrition was required for 14/31
      (45%) patients at 2 years post-Tx. All children had high dietary energy intakes.
      The degree of steatorrhoea was fairly constant, with fat and energy absorption
      rates of 84-89%. Growth parameters revealed at transplantation a mean height Z
      score of -1.17. After Tx, two-thirds of children had normal growth, whereas in
      one-third, Z-scores remained lower than -2, concomitant to a delayed puberty.
      Adult height was normal in 5/6. Endoscopy and histology analyses were normal in
      asymptomatic patients. Chronic rejection occurred only in non-compliant patients.
      Five intestinal grafts were removed 2.5-8 years post-Tx for acute or chronic
      rejection. CONCLUSIONS: This series indicates that long-term intestinal autonomy
      for up to 18 years is possible in the majority of patients after SBTx. Subnormal
      energy absorption and moderate steatorrhoea were often compensated for by
      hyperphagia, allowing normal growth and attainment of adult height. Long-term
      compliance is an important pre-requisite for long-term graft function.

PMID- 18079283
TI  - Preconditioning with death ligands FasL and TNF-alpha protects the cirrhotic
      mouse liver against ischaemic injury.
AB  - BACKGROUND: Ischaemic preconditioning is the preemptive proven strategy to reduce
      ischaemic injury in the liver, but it can be harmful in the elderly or in
      patients with liver diseases. Ischaemic preconditioning induces a protective
      effect via activation of oxidative stress. We hypothesised that Fas ligand and
      tumour necrosis factor alpha can induce a similar response. Therefore, we tested
      if death ligands could mimic ischaemic preconditioning. METHODS: Ischaemia was
      maintained for 60 min in cirrhotic mice. Death ligands were given 40 min before
      ischaemia. Ischaemic injury was assessed by histology and biochemical assays. To
      elucidate the mechanism, we used zinc protophorphyrin, an inhibitor of haem
      oxygenase-1 (HO-1), and gadolinium chloride, an inhibitor of Kupffer cells.
      RESULTS: Compared with the control group, death ligand preconditioning strongly
      reduced all markers of injury: serum transaminase levels, necrosis and apoptosis.
      Preconditioning caused an upregulation of HO-1, predominantly in macrophages.
      When zinc protophorphyrin or gadolinium chloride was applied prior to
      preconditioning, the beneficial effect of preconditioning was lost. CONCLUSION:
      These results demonstrate that ischaemic preconditioning can be replaced by death
      ligand preconditioning in the cirrhotic liver to prevent ischaemic injury. The
      protective mechanism depends on HO-1 induction in macrophages. These results open
      doors for novel hepato-protective strategies in liver surgery and
      transplantation.

PMID- 18079284
TI  - The 10 remaining mysteries of inflammatory bowel disease.

PMID- 18079285
TI  - Visceral hypersensitivity in non-erosive reflux disease.

PMID- 18079286
TI  - Therapy of interferon-induced depression in chronic hepatitis C with citalopram:
      a randomised, double-blind, placebo-controlled study.
AB  - BACKGROUND: Interferon-induced depression represents a major complication in
      antiviral treatment of chronic hepatitis C virus (HCV) infection. AIM: To
      evaluate in a placebo-controlled study the efficacy of a selective serotonin
      reuptake inhibitor (SSRI) in HCV patients on antiviral therapy with interferon
      associated depression. METHODS: 100 HCV outpatients were included in a
      randomised, double-blind, placebo-controlled study. During interferon therapy
      (peginterferon alpha-2b plus ribavirin), depression was monitored using the
      Hospital Anxiety and Depression Scale (HADS). Patients with clinically relevant
      interferon-induced depression (HADS >or=9) were randomly assigned to placebo or
      citalopram (SSRI, 20 mg/day). RESULTS: In 28 patients (28%), HADS scores
      increased to >8 during interferon therapy. They were treated with placebo (n =
      14) or SSRI (n = 14). HADS scores declined significantly in SSRI patients within
      four weeks of therapy (p<0.001) but not in placebo patients. This difference
      between subgroups was statistically significant (p = 0.032). Unblinding became
      necessary in five placebo patients as a result of intolerable depression. Rescue
      medication (20 mg citalopram) led to a significant decrease in HADS scores (p =
      0.008). All citalopram patients were able to complete interferon therapy as
      planned. As an interim analysis showed a significant superiority of SSRI over
      placebo, the study was terminated prematurely. Three patients, who became
      depressed afterwards, were treated in an unblinded fashion with citalopram.
      CONCLUSIONS: The findings demonstrate clearly that citalopram treatment is highly
      effective in HCV patients on interferon therapy, when initiated after the onset
      of clinically relevant depressive symptoms. This suggests that a general SSRI
      prophylaxis is not necessary in these patients.

PMID- 18079287
TI  - Sustained suppression of Bcr-Abl-driven lymphoid leukemia by microRNA mimics.
AB  - Many cancers and leukemias are associated with strong dominant oncogenic
      mutations that activate tyrosine kinases and other classes of molecules,
      including transcription factors and antiapoptotic mechanisms. Some of these
      events can be targeted with small molecules or antibody-based therapeutics, but
      many remain intractable. In addition, cancer-related enzyme targets can often
      mutate, and drug-resistant variants are selected. Therapies directed at the mRNA
      encoding dominant oncogenes could provide a more global set of technologies for
      cancer treatment. To test this concept, we have used the model of transformation
      of hematopoietic cells by the chimeric Bcr-Abl oncogene, a highly activated
      tyrosine kinase. Our results show that tandem arrays of miRNA mimics, but not
      single miRNA mimics, directed against the Abl portion of the mRNA and introduced
      by lentiviral vectors can effectively alter the leukemogenic potency when the
      degree of suppression of expression of Bcr-Abl is reduced >200-fold from control
      levels. Only methods capable of such dramatic sustained reduction in the level of
      expression of highly activated kinase oncogenes are likely to be effective in
      controlling malignant cell populations.

PMID- 18079288
TI  - Raman vs. Fourier transform spectroscopy in diagnostic medicine.

PMID- 18079289
TI  - Neural representations of kinematic laws of motion: evidence for action
      perception coupling.
AB  - Behavioral and modeling studies have established that curved and drawing human
      hand movements obey the 2/3 power law, which dictates a strong coupling between
      movement curvature and velocity. Human motion perception seems to reflect this
      constraint. The functional MRI study reported here demonstrates that the brain's
      response to this law of motion is much stronger and more widespread than to other
      types of motion. Compliance with this law is reflected in the activation of a
      large network of brain areas subserving motor production, visual motion
      processing, and action observation functions. Hence, these results strongly
      support the notion of similar neural coding for motion perception and production.
      These findings suggest that cortical motion representations are optimally tuned
      to the kinematic and geometrical invariants characterizing biological actions.

PMID- 18079290
TI  - Energetics of neuronal signaling and fMRI activity.
AB  - Energetics of resting and evoked fMRI signals were related to localized ensemble
      firing rates (nu) measured by electrophysiology in rats. Two different
      unstimulated, or baseline, states were established by anesthesia. Halothane and
      alpha-chloralose established baseline states of high and low energy,
      respectively, in which forepaw stimulation excited the contralateral primary
      somatosensory cortex (S1). With alpha-chloralose, forepaw stimulation induced
      strong and reproducible fMRI activations in the contralateral S1, where the
      ensemble firing was dominated by slow signaling neurons (SSN; nu range of 1-13
      Hz). Under halothane, weaker and less reproducible fMRI activations were observed
      in the contralateral S1 and elsewhere in the cortex, but ensemble activity in S1
      was dominated by rapid signaling neurons (RSN; nu range of 13-40 Hz). For both
      baseline states, the RSN activity (i.e., higher frequencies, including the gamma
      band) did not vary upon stimulation, whereas the SSN activity (i.e., alpha band
      and lower frequencies) did change. In the high energy baseline state, a large
      majority of total oxidative energy [cerebral metabolic rate of oxygen consumption
      (CMR(O2))] was devoted to RSN activity, whereas in the low energy baseline state,
      it was roughly divided between SSN and RSN activities. We hypothesize that in the
      high energy baseline state, the evoked changes in fMRI activation in areas beyond
      S1 are supported by rich intracortical interactions represented by RSN. We
      discuss implications for interpreting fMRI data where stimulus-specific
      DeltaCMR(O2) is generally small compared with baseline CMR(O2).

PMID- 18079291
TI  - Oscillations in extracellular pH and reactive oxygen species modulate tip growth
      of Arabidopsis root hairs.
AB  - Root hairs show highly localized cell expansion focused to their growing tips.
      This growth pattern is accomplished through restriction of secretion to the
      elongating apex and modulation of cell wall properties, with the wall just behind
      the tip becoming rigidified to resist the lateral expansive forces of turgor. In
      this report we show that root hairs exhibit oscillating growth that is associated
      with oscillating increases in extracellular pH and reactive oxygen species (ROS),
      which lag growth by approximately 7 s. Consistent with a role for these changes
      in growth control, artificially increasing extracellular pH arrested root hair
      elongation, whereas decreasing pH elicited bursting at the tip. Similarly,
      application of exogenous ROS arrested elongation, whereas scavenging of ROS led
      to root hair bursting. Roots hairs of the root hair-defective rhd2-1 mutant,
      which lack a functional version of the NADPH oxidase ATRBOH C, burst at the
      transition to tip growth. This phenotype could be rescued by elevating the pH of
      the growth medium to >/=6.0. Such rescued root hairs showed reduced cytoplasmic
      ROS levels and a lack of the oscillatory production of ROS at the tip. However,
      they exhibited apparently normal tip growth, including generation of the tip
      focused Ca(2+) gradient thought to drive apical growth, indicating that ATRBOH C
      is not absolutely required to sustain tip growth. These observations indicate
      that root hair elongation is coupled to spatially distinct regulation of
      extracellular pH and ROS production that likely affect wall properties associated
      with the polarized expansion of the cell.

PMID- 18079292
TI  - Revealing the bifurcation in the unfolding pathways of GFP by using single
      molecule experiments and simulations.
AB  - Nanomanipulation of biomolecules by using single-molecule methods and computer
      simulations has made it possible to visualize the energy landscape of
      biomolecules and the structures that are sampled during the folding process. We
      use simulations and single-molecule force spectroscopy to map the complex energy
      landscape of GFP that is used as a marker in cell biology and biotechnology. By
      engineering internal disulfide bonds at selected positions in the GFP structure,
      mechanical unfolding routes are precisely controlled, thus allowing us to infer
      features of the energy landscape of the wild-type GFP. To elucidate the
      structures of the unfolding pathways and reveal the multiple unfolding routes,
      the experimental results are complemented with simulations of a self-organized
      polymer (SOP) model of GFP. The SOP representation of proteins, which is a coarse
      grained description of biomolecules, allows us to perform forced-induced
      simulations at loading rates and time scales that closely match those used in
      atomic force microscopy experiments. By using the combined approach, we show that
      forced unfolding of GFP involves a bifurcation in the pathways to the stretched
      state. After detachment of an N-terminal alpha-helix, unfolding proceeds along
      two distinct pathways. In the dominant pathway, unfolding starts from the
      detachment of the primary N-terminal beta-strand, while in the minor pathway
      rupture of the last, C-terminal beta-strand initiates the unfolding process. The
      combined approach has allowed us to map the features of the complex energy
      landscape of GFP including a characterization of the structures, albeit at a
      coarse-grained level, of the three metastable intermediates.

PMID- 18079293
TI  - The Cochrane Neurological Network.

PMID- 18079294
TI  - Locked-in: don't judge a book by its cover.

PMID- 18079295
TI  - Dysexecutive function: family knows best?

PMID- 18079296
TI  - Systematic review: Blood pressure lowering in patients without prior
      cerebrovascular disease for prevention of cognitive impairment and dementia.

PMID- 18079297
TI  - Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and
      unsolved issues.
AB  - Amyotrophic lateral sclerosis (ALS) is a relatively rare disease with a reported
      population incidence of between 1.5 and 2.5 per 100,000 per year. Over the past
      10 years, the design of ALS epidemiological studies has evolved to focus on a
      prospective, population based methodology, employing the El Escorial criteria and
      multiple sources of data to ensure complete case ascertainment. Five such
      studies, based in Europe and North America, have been published and show
      remarkably consistent incidence figures among their respective Caucasian
      populations. Population based studies have been useful in defining clinical
      characteristics and prognostic indicators in ALS. However, many epidemiological
      questions remain that cannot be resolved by any of the existing population based
      datasets. The working hypotheses is that ALS, like other chronic diseases, is a
      complex genetic condition, and the relative contributions of individual
      environmental and genetic factors are likely to be relatively small. Larger
      studies are required to characterise risks and identify subpopulations that might
      be suitable for further study. This current paper outlines the contribution of
      the various population based registers, identifies the limitations of the
      existing datasets and proposes a mechanism to improve the future design and
      output of descriptive epidemiological studies.

PMID- 18079299
TI  - Neurological picture. Elongated styloid process (Eagle's syndrome) as a cause of
      atypical craniocervical pain.

PMID- 18079298
TI  - Neurological picture. Demyelinating butterfly pseudo-glioma.

PMID- 18079300
TI  - Clearance of a status aurae migraenalis in response to thrombendarterectomy in a
      patient with high grade internal carotid artery stenosis.
AB  - We report a patient with high grade internal carotid artery (ICA) stenosis who
      had frequent migrainous aura-like symptoms for a period of 3 weeks (Latin: status
      aurae migraenalis). This syndrome has been described previously but it was
      unclear whether ischaemic damage was associated with it. Using MRI, we
      demonstrated widely scattered focal laminar cortical infarcts. Importantly, after
      ICA thrombendarterectomy, the status aurae migraenalis abruptly ceased which
      supports the concept that high grade ICA stenosis can be the cause of status
      aurae migraenalis.

PMID- 18079301
TI  - Vertebral artery stump syndrome.
AB  - After occlusion of flow in an artery, further ischaemic episodes are not expected
      due to lack of a flow conduit to carry the embolus. In the carotid stump
      syndrome, ongoing ischaemic events may continue due to collateral flow via the
      external carotid artery. We report two patients presenting with posterior
      circulation strokes after documented vertebral artery occlusion, due to a
      vertebral stump syndrome. Their presentation, the pathophysiology of cervico
      vertebral anastomoses and management are described.

PMID- 18079302
TI  - Intravenous immunoglobulin as short- and long-term therapy of multifocal motor
      neuropathy: a retrospective study of response to IVIg and of its predictive
      criteria in 40 patients.
AB  - OBJECTIVE: To document short-term and long-term responses to a single type of
      intravenous immunoglobulin (IVIg) in a large cohort of patients with multifocal
      motor neuropathy (MMN). METHODS: A retrospective study was conducted in 40
      patients with MMN included on ENMC Workshop criteria, and treated with periodic
      IVIg infusions between 1995 and 2003. The short-term response was defined as
      improvement of at least 1 point on the MRC score in at least two affected muscles
      at 6 months. The population comprised 22 treatment-naive patients (who had never
      received IVIg before inclusion), and 18 previously treated patients. For the long
      term evaluation (>6 months), the patients were classified into three groups
      according to the dependency or not on periodic IVIg. In addition, changes in
      conduction block (CB) and predictive criteria for response to IVIg were explored.
      RESULTS: The MRC score significantly improved (p<0.0001) in 14 (70%; 95% CI 0.46
      to 0.88) of the 20 treatment-naive patients (missing data for 2 patients). None
      of the predictive criteria studied were found to be significant. At the end of
      follow-up (mean of 2.2+/-2.0 years), only 8 of the 40 patients (22%) had
      significant remission, whereas 25 patients (68%) were dependent on periodic IVIg
      infusions. The number of CBs decreased or remained unchanged in 12 treatment
      naive patients and increased in 2 such patients. CONCLUSIONS: This study
      confirmed a significantly high short-term response to IVIg of patients with MMN,
      but showed contrasted results in long-term follow-up. No predictive factors for
      response to IVIg were found.

PMID- 18079303
TI  - Neurological picture. Portal-systemic encephalopathy in a non-cirrhotic patient.

PMID- 18079304
TI  - Augusta Dejerine-Klumpke (1859-1927) and her eponym.

PMID- 18079307
TI  - Comparison of a norm-based versus criterion-based approach to measuring ADHD
      symptomatology in college students.
AB  - OBJECTIVE: The prevalence of ADHD symptomatology in college students is unclear
      because rates can vary depending on the methodology that is employed. Gender
      differences in college prevalence have also remained unexplored. METHOD: Self
      reported ADHD symptomatology was assessed in 1,096 college students using the
      College ADHD Response Evaluation, a measure that has been normed on college
      students and that also contains the 18 criteria currently used for diagnosis.
      RESULTS: Almost 20% met the threshold for a modified diagnosis if the 97th
      percentile was used, whereas 7.48% reported the number of symptoms required for
      current diagnostic criteria. Few women reported extreme levels of impulsivity,
      whereas both men and women reported excessive inattention. However, men exceeded
      women in number and severity of inattentive symptoms. CONCLUSION: These findings
      suggest that rates of ADHD symptomatology are higher when college students are
      compared to their peers, which has implications for using current diagnostic
      criteria with this population.

PMID- 18079308
TI  - Mycoplasma pneumoniae infection and obsessive-compulsive disease: a case report.
AB  - It has been demonstrated that obsessive-compulsive disease and/or tic syndromes
      in children may be triggered by an antecedent infection especially with group A
      beta-hemolytic streptococci, and this subgroup of children has been designated by
      the acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated
      with streptococcal infections). Other infectious agents such as viruses and
      bacteria have also been reported to be associated with the acute onset or
      dramatic exacerbation of obsessive-compulsive disease or Tourette syndrome, and
      another acronym, PITAND (pediatric infection-triggered autoimmune
      neuropsychiatric disorder) has appeared in the literature. The involvement of
      other infectious agents such as Mycoplasma pneumoniae has been described in
      single case reports. We describe a case of a 5.5-year-old boy who suddenly
      developed obsessive-compulsive disease symptoms during a M. pneumoniae pneumonia.
      After treatment with oral clarithromycin, all his obsessive-compulsive disease
      symptoms disappeared. To our knowledge, this is the first report that shows the
      association between Mycoplasma pneumoniae infection and obsessive-compulsive
      disease.

PMID- 18079309
TI  - Dietary L-tyrosine supplementation in nemaline myopathy.
AB  - Nemaline myopathy is defined by the presence of nemaline bodies, or rods, on
      muscle biopsy. Facial and bulbar weakness in nemaline myopathy cause chewing and
      swallowing difficulties, recurrent aspiration, and poor control of oral
      secretions. This article discusses 5 patients (4 infants and 1 adolescent) with
      nemaline myopathy who received dietary supplementation with L-tyrosine (250 to
      3000 mg/day). All 4 infants were reported to have an initial decrease in
      sialorrhoea and an increase in energy levels. The adolescent showed improved
      strength and exercise tolerance. No adverse effects of treatment were observed.
      Dietary tyrosine supplementation may improve bulbar function, activity levels,
      and exercise tolerance in nemaline myopathy.

PMID- 18079310
TI  - Effects of postnatal dexamethasone exposure on the developmental outcome of
      premature infants.
AB  - Extremely low birth weight premature infants are at risk for poor
      neurodevelopmental outcome. Postnatal dexamethasone has often been used in
      premature infants to prevent or treat bronchopulmonary dysplasia, and this drug
      is thought by some to affect neurodevelopmental outcome. We retrospectively
      examined the effect of this steroid on early neurodevelopment. Dexamethasone
      exposure was associated with an adverse outcome and was a stronger predictor of
      outcome than other accepted risk factors. If used, dexamethasone should be used
      in these high-risk infants for as short a period as possible.

PMID- 18079311
TI  - Handedness in patients with developmental coordination disorder.
AB  - Developmental coordination disorder affects 5% to 8% of the general population,
      and about 50% to 60% of these children have a comorbid attention-deficit disorder
      with hyperactivity and learning disorders. Left-handedness is relatively common
      among children with dyslexia, learning disabilities, and autism; however, its
      frequency in children with developmental coordination disorder is less clear. The
      present study investigated the distribution of hand dominance in 98 children (age
      range, 5.5-17 years) with developmental coordination disorder compared with their
      parents or siblings. Thirty children (30.6%) were left-handed and 13 (13.3%) were
      ambidextrous. The prevalence of left-handedness among their parents and siblings
      was similar to that of the general population. The results suggest that children
      with developmental coordination disorder, like children with learning disorders
      and deficit disorder with hyperactivity, present with higher frequency of left
      hand dominance compared with the general population.

PMID- 18079312
TI  - Holoprosencephaly and diabetes insipidus in a 3-month-old infant.
AB  - Holoprosencephaly is a developmental defect caused by incomplete cleavage of the
      embryonic forebrain structures during early embryogenesis. We describe a 3-month
      old boy with median cleft palate, surgically reconstructed cleft lip,
      hypotelorism with a flat nose, cryptorchidism, clubfoot, and microcephaly. During
      the laboratory investigation, his blood sodium level was 154 mmol/L and urine
      specific gravity was 1.007. Serum osmolarity was 317 mOsm/kg and urine osmolarity
      was 268 mOsm/kg. Given these findings and the clinical response to vasopressin,
      diagnosis of central diabetes insipidus was made. Magnetic resonance imaging
      revealed semilobar holoprosencephaly. The patient responded very well to
      vasopressin treatment with restoration of serum electrolytes, which remained
      within normal limits on follow-up. In case of midline facial defects accompanied
      by hypotelorism with or without developmental delay, the brain should be imaged
      to confirm its morphology and investigations should be directed by a high index
      of suspicion of associated endocrinologic dysfunctions.

PMID- 18079313
TI  - Autism and metabolic diseases.
AB  - Autism is an etiologic heterogeneous entity caused by many different diseases
      occurring in the central nervous system at an early stage in life. Several
      metabolic defects have been associated with autistic symptoms with a rate higher
      than that found in the general population. Inborn errors of metabolism can
      probably account for less than 5% of individuals. Selective metabolic testing
      should be done in the presence of suggestive clinical findings, including
      lethargy, cyclic vomiting, early seizures, dysmorphic features, and mental
      retardation. In some patients, early diagnosis of the metabolic disorders and
      proper therapeutic interventions may significantly improve the long-term
      cognitive and behavioral outcome.

PMID- 18079314
TI  - Clinical and genetic study in Chinese patients with Alexander disease.
AB  - Alexander disease is a rare progressive leukoencephalopathy inherited in an
      autosomal dominant manner. The infantile form is the most common, with onset
      before 2 years of age. The typical clinical signs include psychomotor retardation
      and regression, seizures, and megalencephaly. Juvenile and adult forms are also
      recognized. The neuropathology of Alexander disease is characterized by abundant
      presence of Rosenthal fibers in astrocytes in the brain. GFAP has been identified
      to be the only gene associated with Alexander disease since 2001. Only 1 patient
      with Alexander disease confirmed by genetic testing has been reported in mainland
      China. To get further information of the clinical and genetic characteristics of
      Chinese patients, we analyzed an additional 3 cases with the infantile or
      juvenile form. A novel mutation, Y83H, and a previously reported mutation, R88C,
      were identified in these patients. Both mutations were heterozygous and de novo.
      The results of this research expand the number of patients with Alexander disease
      found to have GFAP coding mutations in mainland China. A novel missense mutation,
      Y83H, is identified.

PMID- 18079315
TI  - Tumors in the temporal horn of the lateral ventricle as a cause of epilepsy.
AB  - Three neoplastic lesions located in the temporal horn of the lateral ventricle
      were diagnosed after the onset of seizures. Neither hydrocephalus nor temporal
      horn entrapment were present. The complete surgical removal of the tumor resulted
      in the disappearance of the epileptic episodes in 2 cases; the third patient
      refused surgery, and his lesion appears unmodified after a 3-year follow-up.
      Histological examination led to a diagnosis of choroid plexus papilloma in 1 case
      and of neurocytoma in the other; in the third case, the nonextracted lesion was
      presumed to be a partially calcified choroid plexus papilloma. The mechanism
      underlying the seizures in the 2 operated children is speculated to be a
      compression exerted upon the mesial temporal structures that form the medial wall
      of the temporal horn of the lateral ventricles; this compressive activity was
      resolved by removal of the tumor, and the epileptic episodes consequently
      disappeared in the 2 operated children; seizures were controlled by drugs in the
      third child.

PMID- 18079316
TI  - Childhood absence epilepsy with clinically apparent genetic and acquired burdens:
      a diagnostic consideration.
AB  - Both genetic and acquired factors play important roles in the development of
      childhood absence epilepsy. This article describes a girl with mental
      retardation, probably due to a perinatal complication, who had typical absence
      seizures with characteristic electroencephalographic findings of childhood
      absence epilepsy, including normal background activity. This patient was
      subsequently found to have a strong genetic predisposition, which was suggested
      by the fact that childhood absence epilepsy also developed in her younger
      brother. Except for the mental subnormality, the electroclinical features of this
      patient satisfied the diagnostic criteria for childhood absence epilepsy. This
      case raises the question about diagnostic consideration of childhood absence
      epilepsy in association with cerebral pathology for genetically predisposed
      individuals.

PMID- 18079317
TI  - A picture worth remembering: posttraumatic Purtscher's retinopathy in a child.
AB  - Purtscher's retinopathy is frequently described and reviewed in the ophthalmology
      literature but is rarely described in the neurology literature, although
      neurologists are routinely involved in the care of head and chest trauma patients
      with abnormal neurologic and funduscopic findings. The case of a 6-year-old girl
      with Purtscher's retinopathy is described, and the relevant literature is
      reviewed.

PMID- 18079318
TI  - Neurologic complications of liver transplantation in pediatric patients with the
      hepatic form of Wilson's disease.
AB  - The literature contains very little documentation on neurologic complications in
      liver transplant recipients for Wilson's disease. We retrospectively reviewed 17
      consecutive cases of pediatric liver transplantation for the hepatic form of
      Wilson's disease to assess the types of neurologic complications that occurred,
      the incidence of those problems, and associated factors in this patient group.
      The patients were 12 boys and 5 girls; indications for liver transplantation were
      fulminant hepatic failure in 3 patients and chronic hepatic failure in 14
      patients. Neurologic complications were observed in 10 of the 17 patients as 16
      episodes. The most common neurologic complications were seizure (7 episodes in 6
      patients) and sudden-onset headache (5 episodes in 4 patients). Tacrolimus was
      identified as the only possible cause of headache in 3 episodes. Encephalitis was
      the cause in 1 and intracranial hemorrhage was the cause in the other headache
      episode. We also noted 1 episode of tremor, 1 episode of acute dystonic reaction,
      1 episode of diffuse encephalopathy, and 1 episode of common peroneal nerve
      palsy. Immunosuppressive agents were the primary cause of 12 of the 16 episodes
      of neurologic complications. Uremia with hypertension, compression of the right
      common peroneal nerve, encephalitis, and intracranial hemorrhages attributable to
      coagulopathy caused 1 neurologic episode each. Neurologic complications in
      patients with the hepatic form of Wilson's disease were frequent during the first
      30 days after pediatric liver transplantation but did not affect survival.
      Transplantation teams should be aware of the high incidence of neurologic
      complications in pediatric patients with the hepatic form of Wilson's disease.

PMID- 18079319
TI  - Role of continuous positive airway pressure therapy on the pathogenesis of sleep
      related frontal lobe epilepsy in a child with obstructive sleep apnea syndrome.
AB  - We describe an obese child with severe obstructive sleep apnea syndrome in whom
      nocturnal frontal lobe seizures developed within a week after therapy was started
      with continuous positive airway pressure. The video polysomnographic study after
      the onset of nocturnal episodes showed 3 seizures: 2 starting from slow-wave
      sleep when he was sleeping with continuous positive airway pressure, and 1 from
      stage 2 non-rapid eye movement sleep when he was sleeping without continuous
      positive airway pressure. Cyclic alternating pattern analysis during the video
      polysomnography recorded after the onset of nocturnal seizures disclosed a high
      cyclic alternating pattern rate during slow-wave sleep, and the recording
      obtained after antiepileptic therapy began showed a low cyclic pattern analysis
      rate. In this child, we describe the non-rapid eye movement sleep instability
      induced by continuous positive airway pressure therapy might have had a role in
      triggering the nocturnal seizures.

PMID- 18079320
TI  - Canadian adolescents with migraine: impaired health-related quality of life.
AB  - The objective of this study was to determine the impact of migraine headaches on
      health-related quality of life among Canadian adolescents. The Canadian Community
      Health Survey (CCHS) collects information related to health status, health care
      utilization, and health determinants for the Canadian population. Analysis was
      limited to those adolescents 12-19 years of age residing in Manitoba. Respondents
      reported whether they had migraine and mood/anxiety disorders. Health-related
      quality of life was measured using the Short Form-36 survey, which covers 8
      health concepts related to functional status, well-being, and overall health.
      Multivariate linear regression analysis was used to model each Short Form-36
      scale against age (12-14 years vs 15-19 years), gender, migraine, and the
      presence of a mood or anxiety disorder. The CCHS was completed by 994
      respondents; 9.3% (95% confidence interval, 7.3%-11.5%) reported a diagnosis of
      migraine. Reported migraine predicted both statistically (P < .0001) and
      clinically significantly lower health-related quality of life in all Short Form
      36 domains except vitality and general health perceptions. Adolescents reporting
      a mood disorder (2.1%) scored significantly lower in 6 of 8 health-related
      quality of life domains, most pronounced for emotional role, general mental
      health, and social functioning. Canadian adolescents with migraine report
      clinically and statistically significant impairment in health-related quality of
      life compared to their peers, independent of psychiatric comorbidities.

PMID- 18079321
TI  - Ligand-independent activation of androgen receptors by Rho GTPase signaling in
      prostate cancer.
AB  - Prostate cancer invariably recurs after androgen deprivation therapy. Growth of
      this recurrent/androgen-independent form of prostate cancer may be due to
      increased androgen receptor (AR) transcriptional activity in the absence of
      androgen. This ligand-independent AR activation is promoted by some growth
      factors but the mechanism is not well understood. Vav3, a Rho guanosine
      triphosphatase guanine nucleotide exchange factor, which is activated by growth
      factors, is up-regulated in human prostate cancer. We show here that Vav3 levels
      increase during in vivo progression of prostate cancer to androgen independence.
      Vav3 strikingly enhanced growth factor activation of AR in the absence of
      androgen. Because Vav3 may be chronically activated in prostate cancer by growth
      factor receptors, we examined the effects of a constitutively active (Ca) form of
      Vav3 on AR transcriptional activity. Ca Vav3 caused nuclear localization and
      ligand-independent activation of AR via the Rho guanosine triphosphatase, Rac1.
      Ca Rac1 activation of AR occurred, in part, through MAPK/ERK signaling.
      Expression of active Rac1 conferred androgen-independent growth of prostate
      cancer cells in culture, soft agar, and mice. These findings suggest that
      Vav3/Rac 1 signaling is an important modulator of ligand-independent AR
      transcriptional activity in prostate cancer progression.

PMID- 18079324
TI  - Social justice in the land of Cockaigne.

PMID- 18079322
TI  - Glucocorticoid/glucocorticoid receptor inhibition of surfactant protein-A (SP-A)
      gene expression in lung type II cells is mediated by repressive changes in
      histone modification at the SP-A promoter.
AB  - Surfactant protein-A (SP-A) gene expression in human fetal lung type II cells is
      stimulated by cAMP and IL-1 and is inhibited by glucocorticoids. cAMP/IL-1
      stimulation of SP-A expression is mediated by increased binding of thyroid
      transcription factor-1 and nuclear factor (NF)-kappaB to the TTF-1-binding
      element (TBE) in the SP-A promoter. This is associated with decreased expression
      of histone deacetylases (HDACs), increased recruitment of coactivators, and
      enhanced acetylation of histone H3 (K9,14) at the TBE. In the present study,
      endogenous glucocorticoid receptor (GR) was found to interact with thyroid
      transcription factor-1 and NF-kappaB p65 at the TBE. GR knockdown enhanced SP-A
      expression in type II cells cultured in serum-free medium, suggesting a ligand
      independent inhibitory role of endogenous GR. Furthermore, use of chromatin
      immunoprecipitation revealed that dexamethasone (Dex) treatment of fetal lung
      type II cells increased recruitment of endogenous GR and HDACs-1 and -2 and
      blocked cAMP-induced binding of inhibitor of kappaB kinase-alpha (IKKalpha) to
      the TBE region. Accordingly, Dex reduced basal and blocked cAMP-stimulated levels
      of acetylated (K9,14) and phosphorylated (S10) histone H3 at the TBE. Dex also
      increased TBE binding of dimethylated histone H3 (K9) and of heterochromatin
      protein 1alpha. Thus, Dex increases interaction of GR with the complex of
      proteins at the TBE. This facilitates recruitment of HDACs and causes a local
      decline in basal and cAMP-induced histone H3 phosphorylation and acetylation and
      an associated increase in H3-K9 dimethylation and binding of heterochromatin
      protein 1alpha. Collectively, these events may culminate in the closing of
      chromatin structure surrounding the SP-A gene and inhibition of its
      transcription.

PMID- 18079325
TI  - The welfare state: a glossary for public health.
AB  - Recently, there has been a surge in comparative social epidemiology, and a
      sizeable amount of this has examined the relation between different aspects of
      the welfare state and population health. Such research draws strongly, though
      usually implicitly, on welfare state theories and concepts. In this glossary, we
      explicitly define these concepts in order to enable more researchers,
      practitioners and policy-makers to engage with and contribute to this exciting
      and fruitful area of public health research.

PMID- 18079323
TI  - Modulation of in situ estrogen synthesis by proline-, glutamic acid-, and leucine
      rich protein-1: potential estrogen receptor autocrine signaling loop in breast
      cancer cells.
AB  - In situ estrogen synthesis is implicated in tumor cell proliferation through
      autocrine or paracrine mechanisms especially in postmenopausal women. Several
      recent studies demonstrated activity of aromatase, an enzyme that plays a
      critical role in estrogen synthesis in breast tumors. Proline-, glutamic acid-,
      and leucine-rich protein-1 (PELP1/MNAR) is an estrogen receptor (ER) coregulator,
      and its expression is deregulated in breast tumors. In this study, we examined
      whether PELP1 promotes tumor growth by promoting local estrogen synthesis using
      breast cancer cells (MCF7) that stably overexpress PELP1. Immunohistochemistry
      revealed increased aromatase expression in MCF7-PELP1-induced xenograft tumors.
      Real-time PCR analysis showed enhanced activation of the aromatase promoter in
      MCF7-PELP1 clones compared with MCF7 cells. Using a tritiated-water release
      assay, we demonstrated that MCF7-PELP1 clones exhibit increased aromatase
      activity compared with control MCF-7 cells. PELP1 deregulation uniquely up
      regulated aromatase expression via activation of aromatase promoter I.3/II, and
      growth factor signaling enhanced PELP1 activation of aromatase. PELP1-mediated
      induction of aromatase requires functional Src and phosphatidylinositol-3-kinase
      pathways. Mechanistic studies revealed that PELP1 interactions with ER-related
      receptor-alpha and proline-rich nuclear receptor coregulatory protein 2 lead to
      activation of aromatase. Immunohistochemistry analysis of breast tumor array
      showed increased expression of aromatase in ductal carcinoma in situ and node
      positive tumors compared with no or weak expression in normal breast tissue.
      Fifty-four percent (n = 79) of PELP1-overexpressing tumors also overexpressed
      aromatase compared with 36% (n = 47) in PELP1 low-expressing tumors. Our results
      suggest that PELP1 regulation of aromatase represents a novel mechanism for in
      situ estrogen synthesis leading to tumor proliferation by autocrine loop and open
      a new avenue for ablating local aromatase activity in breast tumors.

PMID- 18079326
TI  - Information is not good enough: the transformation of health education in France
      in the late 1970s.
AB  - The aim of this article is to provide a historical account of the many problems
      that arose in the making of large-scale health education campaigns in France,
      from the mid-1970s to the mid-1980s, as well as the solution explored at that
      time. Fascination for the alleged influence of mass media on human behaviour
      prompted a government keen on anything "modern" to implement the first ever large
      scale health education campaign on the risks of "excessive smoking." However, the
      hyper-rationalistic approach to communication favoured by the French Committee
      for Health Education (FCHE), in charge of the campaign, prompted many questions
      concerning both the impact, and the political implications of their approach. The
      historical investigation described here is based on the study of various kinds of
      propaganda material; interviews with health education specialists and senior
      civil servants; and the systematic exploration of the archives produced by the
      FCHE. The analysis of the issues raised by this policy, as well as the answers
      provided by the protagonists themselves, sheds new light on pending questions in
      health education, such as the need to reconcile political acceptability and
      effectiveness, and the role that social sciences might play in this process.

PMID- 18079327
TI  - The effect of smoke-free policies on electronic gaming machine expenditure in
      Victoria, Australia.
AB  - OBJECTIVE: To examine the impact of smoke-free policies in Victorian gambling
      venues on electronic gaming machine (EGM) expenditure. METHOD: Monthly EGM
      expenditure from July 1998 to December 2005, provided by the Victorian Commission
      for Gambling Regulation and the Office of the Liquor and Gambling Commissioner in
      South Australia, was analysed. The outcome measure was the ratio of monthly
      expenditure for Victoria to monthly expenditure in South Australia. Intervention
      analysis and autoregressive integrated moving average modelling were used to
      assess the impact of the smoke-free policy on expenditure. RESULTS: The smoke
      free policy resulted in an abrupt, long-term decrease in the level of EGM
      expenditure. The mean level of monthly expenditure decreased by approximately
      14%. CONCLUSION: The smoke-free policy not only protects hospitality workers and
      patrons from exposure to secondhand smoke but has also had an impact on slowing
      gambling losses.

PMID- 18079328
TI  - Previous abortion and the risk of low birth weight and preterm births.
AB  - OBJECTIVE: To investigate the association between previous abortion and low birth
      weight (LBW) and preterm birth (PB). METHOD: The study examined live, singleton
      births using data from the United States Collaborative Perinatal Project.
      Logistic regression was used to control for obstetric and medical history, and
      lifestyle and demographic factors. RESULT: Compared with women with no history of
      abortion, women who had one, two and three or more previous abortions were 2.8
      (95% CI 2.48 to 3.07), 4.6 (95% CI 3.94 to 5.46) and 9.5 (95% CI 7.72 to 11.67)
      times more likely to have LBW, respectively. The risk for PB was also 1.7 (95% CI
      1.52 to 1.83), 2.0 (95% CI 1.73 to 2.37) and 3.0 (95% CI 2.47 to 3.70) times
      higher for women with a history of one, two and three or more previous abortions,
      respectively. CONCLUSION: Previous abortion is a significant risk factor for LBW
      and PB, and the risk increases with the increasing number of previous abortions.
      Practitioners should consider previous abortion as a risk factor for LBW and PB.

PMID- 18079329
TI  - Impaired childhood development and suicidal behaviour in a cohort of Danish men
      born in 1953.
AB  - BACKGROUND: Few studies have examined the correlation between social
      circumstances during childhood and adult suicide behaviour in a prospective
      design. How indicators of impaired childhood development affect the risk of
      suicide behaviour before the age of 50 years are analysed in this study. METHOD:
      9359 Men born in Copenhagen, Denmark, in 1953, who had completed conscription
      medical examination at approximately 18 years of age and for whom birth
      certificates had been traced were followed from 1972 to 2003 in Danish health
      registers regarding suicide or suicide attempts. At the age of 12 years 6856 of
      these cohort members had completed a cognitive performance test. RESULTS: During
      follow-up, 92 (1.0%) and 228 (2.4%) of the men, respectively, committed suicide
      or had one or more suicide attempt. Low body mass index (BMI), low cognitive test
      score, and mental disorder at the age of 18 years were associated with an
      increased risk of suicide. After adjustment, mental disorder remained
      significantly associated with suicide risk (hazard ratio 2.49, 95% CI 1.03 to
      6.02), whereas the estimates for cognitive function (HR 0.77, 95% CI 0.59 to
      1.01) and BMI (HR 0.81, 95% CI 0.64 to 1.02) were attenuated. In the crude
      analyses suicide attempt was associated with all indicators, but after adjustment
      mental disorder (HR 2.64 (95% CI 1.55 to 4.49), no more than a basic school
      education (HR 2.28, 95% CI 1. 30 to 4.00), BMI (HR 0.87, 95% CI 0.75 to 1.00) and
      cognitive test score at the age of 18 years (HR 0.85, 95% CI 0.72 to 1.01) were
      associated with the risk of suicide attempt. CONCLUSION: This study suggests that
      low BMI, low cognitive function, and mental disorder in early adulthood are
      markers of an increased risk of suicide among men born in Denmark in 1953.

PMID- 18079330
TI  - Life course influence of residential area on cause-specific mortality.
AB  - OBJECTIVE: To examine the relative influence of area of residence on mortality
      risk along the life course in different age groups and to see if this differs for
      causes known to be related differently to various models of the life course.
      METHODS: Individual data from the Censuses in 1960, 1970, 1980 and 1990 from
      Oslo, Norway, were linked to the death register 1990-1998. All male inhabitants
      living in Oslo in 1990 aged 30-69 years who had lived in Oslo at the three
      previous Censuses were included. RESULTS: In the youngest age group, area of
      residence closest to the time of death is most important for violent and
      psychiatric causes. In older age groups, area of residence at all time points in
      the period studied seemed to have a similar influence. Cardiovascular deaths were
      related to earlier as well as later area of residence in both young and old age
      groups. For violent and psychiatric causes, the most recent area may be the most
      important. CONCLUSION: This paper explores a research strategy to investigate how
      the area of residence through the life course influences mortality. The
      associations seem to vary according to age at, and cause of, death.

PMID- 18079331
TI  - The sense of coherence and risk of injuries: role of alcohol consumption and
      occupation.
AB  - STUDY OBJECTIVE: To test the hypothesis that individuals with a strong sense of
      coherence (SOC) have a decreased incidence of external cause injuries and to
      study the role of alcohol consumption and occupational category in that
      association. DESIGN: Participants of the Helsinki Heart Study were followed up
      for injuries for eight years through the national hospital discharge register and
      cause of death statistics. Cox proportional hazards models were used to calculate
      the relative risks. SETTING: The Helsinki Heart Study, a clinical trial to
      prevent coronary heart disease. PARTICIPANTS: 4405 Finnish middle-aged employed
      men. MAIN RESULTS: The SOC was inversely associated with the risk of injuries,
      with a significant 25% lower incidence in the highest tertile of SOC (7.6 per
      1000 person-years) compared with the lowest (10.2 per 1000 person-years). The
      association remained significant if adjusted for age, but not if adjusted
      additionally for alcohol consumption or occupation. When considered jointly with
      occupational category, the injury risk showed a decreasing trend (p = 0.02) with
      increasing SOC among blue collar but not among white collar workers. The use of
      alcohol had a great impact on injury risk among those with weak SOC, with
      incidences of 7.7, 10.2, and 14.9 per 1000 person-years in the non/light, medium,
      and heavy categories of consumption (p for trend 0.01). No such trend was seen in
      other SOC tertiles. CONCLUSIONS: There was an effect of SOC on the incidence of
      injury especially among blue collar workers. A substantial part of the effect was
      mediated by alcohol consumption.

PMID- 18079332
TI  - The relationship between work stress and mental disorders in men and women:
      findings from a population-based study.
AB  - OBJECTIVES: [corrected] This analysis estimated the gender-specific associations
      between work stress, major depression, anxiety disorders and any mental disorder,
      adjusting for the effects of demographic, socioeconomic, psychological and
      clinical variables. METHODS: Data from the Canadian national mental health survey
      were used to examine the gender-specific relationships between work stress
      dimensions and mental disorders in the working population (n = 24,277). Mental
      disorders were assessed using a modified version of the World Mental Health -
      Composite International Diagnostic Interview. RESULTS: In multivariate analysis,
      male workers who reported high demand and low control in the workplace were more
      likely to have had major depression (OR 1.74, 95% CI 1.12 to 2.69) and any
      depressive or anxiety disorders (OR 1.47, 95% CI 1.05 to 2.04) in the past 12
      months. In women, high demand and low control was only associated with having any
      depressive or anxiety disorder (OR 1.39, 95% CI 1.05 to 1.84). Job insecurity was
      positively associated with major depression in men but not in women. Imbalance
      between work and family life was the strongest factor associated with having
      mental disorders, regardless of gender. CONCLUSIONS: Policies improving the work
      environment may have positive effects on workers' mental health status. Imbalance
      between work and family life may be a stronger risk factor than work stress for
      mental disorders. Longitudinal studies incorporating important workplace health
      research models are needed to delineate causal relationships between work
      characteristics and mental disorders.

PMID- 18079333
TI  - The associations between height components (leg and trunk length) and adult
      levels of liver enzymes.
AB  - STUDY OBJECTIVE: To examine the separate associations of leg length, a biomarker
      of prepubertal exposures and growth, and trunk length with adult levels of liver
      enzymes: alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT),
      aspartate transaminase (AST) and alkaline phosphatase (ALP). METHODS: A cross
      sectional analysis of baseline data from the British Women's Health and Heart
      Study, a random sample of British women aged 60-79 years. RESULTS: Leg length was
      inversely associated with age-adjusted levels of ALT, GGT and ALP. These
      associations remained when controlling for childhood and adulthood social class,
      physical activity, smoking, alcohol consumption, waist-to-hip ratio and trunk
      length. Trunk length was positively associated with ALT and inversely associated
      with ALP and the associations remained when adjusting for covariables.
      CONCLUSIONS: Adult liver function is affected by early life environmental
      exposures as reflected in leg length, and this may suggest common childhood
      influences on liver development and adult risk of diabetes and coronary heart
      disease. Further studies with detailed measures of early life exposures relevant
      to leg length would be valuable in identifying any specific exposures
      contributing to adult liver function and cardiovascular disease.

PMID- 18079334
TI  - Examining the relationships between job control and health status: a path
      analysis approach.
AB  - OBJECTIVE: To examine the pathways through which job control affects health
      status; to examine if the effects of job control on health status are attenuated
      by including other measures associated with lower socioeconomic status, and to
      examine if the relationship between job control and health status is consistent
      across socioeconomic status groups. DESIGN: A prospective observational cohort
      study over eight years (1994-2002). PARTICIPANTS: 4886 Respondents aged 25-60
      years, who were non-self-employed labour force participants, working more than 20
      hours per week, without physical or mental limitations restricting the type or
      amount of work they could do at baseline. After longitudinal attrition, the
      remaining study sample was 3411 (87% of the original study sample who did not die
      or become pregnant during the survey period). MAIN RESULTS: Low job control in
      1994 was associated with worse than expected self-rated health in 2002, both
      directly and indirectly via a lower physical activity level in 1996. Adjustment
      for other factors associated with low socioeconomic status did not attenuate
      these relationships to a large extent. No differences were found in the effects
      of job control on physical activity or health status between socioeconomic groups
      (high and low education and high and low household income). CONCLUSIONS: The
      inclusion of other factors associated with lower socioeconomic status did not
      attenuate the direct and indirect effects of job control on health status. The
      finding that low job control is associated with lower physical activity levels
      deserves further investigation, given the increasing concern about rising levels
      of obesity in the developed world.

PMID- 18079335
TI  - Neighbourhood social interactions and risk of acute myocardial infarction.
AB  - STUDY OBJECTIVE: Previous studies of neighbourhood effects on ischaemic heart
      disease (IHD) have used census or administrative data to characterise the
      residential context, most commonly its socioeconomic level. Using the ecometric
      approach to define neighbourhood social interaction variables that may be
      relevant to IHD, neighbourhood social cohesion and safety were examined to see
      how they related to acute myocardial infarction (AMI) mortality, after adjustment
      for individual and neighbourhood confounders. DESIGN: To construct social
      interaction variables, multilevel models were used to aggregate individual
      perceptions of safety and cohesion at the neighbourhood level. Linking data from
      the Health Survey in Scania, Sweden, and the Population, Hospital, and Mortality
      Registers, multilevel survival models were used to investigate determinants of
      AMI mortality over a three year and nine month period. PARTICIPANTS: 7791
      Individuals aged 45 years and over. MAIN RESULTS: The rate of AMI mortality
      increased with decreasing neighbourhood safety and cohesion. After adjustment for
      individual health and socioeconomic variables, low neighbourhood cohesion, and to
      a lesser extent low safety, were associated with higher AMI mortality.
      Neighbourhood cohesion effects persisted after adjustment for various
      neighbourhood confounding factors (income, population density, percentage of
      residents from low-income countries, residential stability) and distance to the
      hospital. There was some evidence that neighbourhood cohesion effects on AMI
      mortality were caused by effects on one-day case-fatality, rather than on
      incidence. CONCLUSIONS: Beyond commonly evoked effects of the physical
      environment, neighbourhood social interaction patterns may have a decisive
      influence on IHD, with a particularly strong effect on survival after AMI.

PMID- 18079336
TI  - Could ultraviolet B irradiance and vitamin D be associated with lower incidence
      rates of lung cancer?
AB  - BACKGROUND: This study examines whether insufficient ultraviolet B (UVB)
      irradiance, a marker of vitamin D inadequacy, might contribute to lung cancer
      incidence. METHODS: The association of latitude and UVB irradiance with age
      adjusted incidence rates of lung cancer in 111 countries was investigated.
      Independent associations with UVB irradiance, cloud cover, anthropogenic
      aerosols, and cigarette smoking, were assessed using multiple regression.
      RESULTS: Latitude was positively related to incidence rates in men (R(2) = 0.55,
      p<0.01) and women (R(2) = 0.36, p<0.01). In men, cigarette consumption (p<0.001)
      was positively related to risk, whereas UVB irradiance was inversely associated
      (p = 0.003). There were positive associations with UVB absorbers, in particular
      cloud cover (p = 0.05) and aerosol optical depth (p = 0.005). The R(2) for the
      model was 0.78 (p<0.001). UVB irradiance was also inversely associated with
      incidence rates in women (p = 0.0002), whereas cigarette consumption (p<0.001),
      total cloud cover (p = 0.02) and aerosol optical depth (p = 0.005) were
      positively associated. The R(2) for the model was 0.77 (p<0.001). CONCLUSIONS:
      Lower levels of UVB irradiance were independently associated with higher
      incidence rates of lung cancer in 111 countries.

PMID- 18079337
TI  - Are social inequalities in mortality in Britain narrowing? Time trends from 1978
      to 2005 in a population-based study of older men.
AB  - OBJECTIVE: To examine whether social inequalities in all-cause and coronary heart
      disease (CHD) mortality in Britain have reduced between 1978 and 2005. DESIGN: A
      prospective study of a socioeconomically representative population. SETTING: 24
      British towns. PARTICIPANTS: 7735 Men, aged 40-59 years at recruitment in 1978
      1980 and followed up until 2005 through the National Health Service Central
      Register (164 120 person-years). MAIN OUTCOME MEASURES: Relative hazards and
      absolute risk differences for all-cause and CHD death comparing manual with non
      manual social classes, calculated for different calendar periods. RESULTS: 3009
      Deaths from all causes (1003 from CHD) occurred during follow-up. The overall
      hazard ratio (manual versus non-manual) was 1.56 (95% CI 1.45 to 1.69, p<0.001)
      for all-cause mortality and 1.54 (95% CI 1.35 to 1.76, p<0.001) for CHD
      mortality. The relative difference between these social groups tended to increase
      over time. The overall relative increase in hazard ratio comparing manual with
      non-manual groups over a 20-year calendar period was 1.22 (95% CI 0.83 to 1.80, p
      = 0.31) for all-cause mortality and 1.75 (95% CI 0.89 to 3.45, p = 0.11) for CHD
      mortality. The absolute difference in probability of survival to age 65 years
      between non-manual and manual groups fell from 29% in 1981 to 19% in 2001 for all
      cause mortality and from 17% to 7% for CHD mortality. CONCLUSION: Relative
      differences in all-cause and CHD mortality between manual and non-manual social
      class groups persisted and may have increased during this period. Absolute
      differences in mortality between these social groups decreased as a result of
      falling overall mortality rates. Greater effort is needed to reduce social
      inequalities in all-cause and CHD mortality in the new millennium.

PMID- 18079338
TI  - The effects of question order and response-choice on self-rated health status in
      the English Longitudinal Study of Ageing (ELSA).
AB  - BACKGROUND: One of the most ubiquitous global health measures is a single self
      rated health item. This item may be sensitive to its position in questionnaires
      and to response-choice wording. The aims of this paper were to investigate the
      effects of question order and response choice on self-reported health status.
      METHOD: A secondary analysis of wave 1 of the English Longitudinal Study of
      Ageing (ELSA). Participants were a nationally representative sample of people
      aged 50 years and over living at home. Over 11 000 respondents were interviewed
      face-to-face in their homes, and were randomly assigned to one of two versions of
      a self-rated health item. RESULTS: The health status item asked after, rather
      than before, a module of health questions, resulted in more optimal health
      assessments, although the effect size was small. The version of the health status
      item with "excellent", rather than "very good" as the first response category
      resulted in more optimal health assessments, although it had a smaller ceiling
      effect. CONCLUSIONS: There was support for the insertion of the health status
      question at the beginning of health questionnaires, as it may be influenced by
      questions about health and disease if placed at the end, although the effect size
      was small. Evidence for the version of the item with "excellent", rather than
      "very good", as the first response choice was more mixed as, although optimism
      bias appeared higher, the ceiling effects were lower. The smaller ceiling effects
      for the "excellent" version has important implications for the ability to detect
      improvements in follow-up studies.

PMID- 18079343
TI  - Amyloidosis of the mesentery and small intestine presenting as a mesenteric
      haematoma.
AB  - Amyloidosis involving the mesentery is very rare, and its radiological appearance
      has been poorly documented. To our knowledge, this is the first case of
      amyloidosis involving the mesentery being presented as a mesenteric haematoma.

PMID- 18079344
TI  - Pulmonary metastatic microangiopathy of colon cancer presenting as a "tree in
      bud" pattern.
AB  - The authors report an unusual case of a "tree in bud" pattern of vascular origin
      caused by colon cancer metastases. A 60-year-old man presented for routine follow
      up of a colon tumour resected surgically 15 years previously. Clinical
      examination, laboratory tests, including carcino-embryonic antigen and
      inflammatory parameters, and chest radiograph were normal. Multislice CT of the
      lungs revealed the presence of several "tree in bud" opacities. The connection to
      the pulmonary arteries was well depicted by reformatted maximal intensity
      projection images. Biopsy of some of the nodules was characterized by mucinous
      material and neoplastic cells within the small vessels, consistent with
      metastases from the known colon adenocarcinoma.

PMID- 18079345
TI  - Spontaneous pancreatic pseudocyst-portal vein fistula presenting with pancreatic
      ascites: strength of MR cholangiopancreatography.
AB  - Pancreatic pseudocyst-portal vein fistulae are a very rare complication of acute
      or chronic pancreatitis. Another late complication of chronic pancreatitis is
      pancreatic ascites. We report the case of a 43-year-old man with a spontaneous
      pseudocyst-portal vein fistula presenting with pancreatic ascites diagnosed by
      various imaging modalities, in order to emphasize the strength and efficacy of
      magnetic resonance cholangiopancreatography.

PMID- 18079346
TI  - Familial colonic varices--a cause of "polyposis" on barium enema.
AB  - A 61-year-old woman with diarrhoea had multiple filling defects on a barium enema
      and was assumed to have multiple colonic polyps. However, colonoscopy showed
      colonic varices and relatively few true polyps. She bled significantly after
      polypectomy of a tubular adenoma. There was no evidence to support a diagnosis of
      portal hypertension or liver disease. A case report of her father's idiopathic
      colonic varices has previously been reported in this journal in 1985, and we
      update his subsequent progress and discuss other reports of this rare condition.

PMID- 18079347
TI  - Spontaneous resolution of a colloid cyst of the third ventricle.
AB  - We report a case of an asymptomatic colloid cyst of the third ventricle in a 35
      year-old male, which on follow-up MRI at 15 months appears to have spontaneously
      resolved. To our knowledge, this is the first such case reported and supports the
      role of conservative management of small asymptomatic colloid cysts.

PMID- 18079348
TI  - PET scanning and Gamma Knife radiosurgery in the early diagnosis and salvage
      "cure" of locally recurrent nasopharyngeal carcinoma.
AB  - "Gamma Knife radiosurgery" is high-dose conformal radiation therapy used for the
      treatment of small target lesions in the head. It is a minimally invasive
      technique of multiple fixed, precisely aimed cobalt beams, and relies upon strict
      patient immobilization via a pinned stereotactic frame to deliver treatment to a
      precisely located target within a coordinated mapping system. This technique has
      been widely validated for the treatment of intra-cranial neoplasms and
      arteriovenous malformations. In this manuscript, two cases of early diagnosed,
      locally recurrent (persistent) nasopharyngeal carcinoma, successfully treated by
      Gamma Knife, are described. In one of these, early diagnosis by PET scanning may
      have improved the chance of cure.

PMID- 18079349
TI  - Plicae palmatae of the cervical canal visualized on MRI.
AB  - We report a case in which plicae palmatae (a normal anatomical structure of the
      cervix) was demonstrated on MRI. A 33-year-old woman with endometrial cancer
      underwent a pre-operative MRI examination before total abdominal hysterectomy.
      Axial T2 weighted images through the cervix demonstrated a longitudinal line of
      distinct hypointensity confined to the cervical canal. Gross examination of the
      surgical specimen revealed a relatively large median longitudinal ridge, as well
      as shorter folds fanning out laterally and upward, which were clearly
      identifiable on the endocervical wall. The midline longitudinal ridge was
      considered to represent a portion of the plicae palmatae, which are folds on the
      anterior and posterior walls of the uterine cervical canal. On MRI, one should
      avoid misdiagnosing this line of hypointensity as a septate uterus.

PMID- 18079350
TI  - Acute parent artery dissection as a complication of mesenteric endovascular coil
      embolisation for pancreatic pseudoaneurysm.
AB  - We wish to highlight arterial dissection as an unusual complication during
      endovascular coiling of a pancreatic pseudoaneurysm. Immediate recognition and
      prompt corrective measures prevented progression of this serious condition. In
      our patient, angioplasty prevented further propagation of the dissection and
      preserved coeliac artery patency.

PMID- 18079351
TI  - Minimal ionizing radiation sensitivity in a large cohort of xeroderma pigmentosum
      fibroblasts.
AB  - We have examined our ionizing radiation survival data for 33 xeroderma
      pigmentosum (XP) primary fibroblast lines and compared the data to that of 53
      normal fibroblast lines, 7 Cockayne syndrome (CS) lines, 4 combined XP/CS lines
      and 8 ataxia-telangiectasia fibroblast lines. Although there are differences in
      radiosensitivity between cell lines within each class, we have no convincing
      evidence that XP lines as a group are more sensitive to ionizing radiation than
      the general population. However, because the XP phenotype may lead to premature
      ageing, especially of sun-exposed tissues, we would still advocate caution when
      XP patients come to radiotherapy. Our results confirm the extreme ionizing
      radiation hypersensitivity of ataxia-telangiectasia; they are also consistent
      with a tendency for slight hypersensitivity in CS, but not (necessarily) in
      combined XP/CS.

PMID- 18079352
TI  - A child with cerebellar ataxia.

PMID- 18079354
TI  - 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous
      Coronary Intervention: a report of the American College of Cardiology/American
      Heart Association Task Force on Practice Guidelines: 2007 Writing Group to Review
      New Evidence and Update the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous
      Coronary Intervention, Writing on Behalf of the 2005 Writing Committee.

PMID- 18079355
TI  - Increased C-fiber nociceptive input potentiates inhibitory glycinergic
      transmission in the spinal dorsal horn.
AB  - Glycine is an important inhibitory neurotransmitter in the spinal cord, but it
      also acts as a coagonist at the glycine site of N-methyl-d-aspartate (NMDA)
      receptors to potentiate nociceptive transmission. However, little is known about
      how increased nociceptive inflow alters synaptic glycine release in the spinal
      dorsal horn and its functional significance. In this study, we performed whole
      cell recordings in rat lamina II neurons to record glycinergic spontaneous
      inhibitory postsynaptic currents (sIPSCs). The transient receptor potential
      vanilloid receptor 1 agonist capsaicin caused a prolonged increase in the
      frequency of sIPSCs in 17 of 25 (68%) neurons tested. The potentiating effect of
      capsaicin on sIPSCs was blocked by ionotropic glutamate receptor antagonists or
      tetrodotoxin in most lamina II neurons examined. In contrast, the P2X agonist
      alphabeta-methylene-ATP increased sIPSCs in only two of 16 (12.5%) neurons. The
      glutamate transporter inhibitor l-trans-pyrrolidine-2,4-dicarboxylic acid either
      increased or reduced the basal frequency of sIPSCs but did not significantly
      alter the potentiating effect of capsaicin on sIPSCs. Furthermore, the groups II
      and III metabotropic glutamate receptor antagonists had no significant effect on
      the capsaicin-induced increase in the sIPSC frequency. Although capsaicin reduced
      the amplitude of evoked excitatory postsynaptic currents at high stimulation
      currents, it did not change the ratio of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid/NMDA currents. This study provides the important new
      information that increased nociceptive inflow augments synaptic glycine release
      to spinal dorsal horn neurons through endogenous glutamate release. Potentiation
      of inhibitory glycinergic tone by stimulation of nociceptive primary afferents
      may function as a negative feedback mechanism to attenuate nociceptive
      transmission at the spinal level.

PMID- 18079356
TI  - Statins decrease expression of the proinflammatory neuropeptides calcitonin gene
      related peptide and substance P in sensory neurons.
AB  - Clinical and experimental observations suggest that statins may be useful for
      treating diseases presenting with predominant neurogenic inflammation, but the
      mechanism(s) mediating this potential therapeutic effect are poorly understood.
      In this study, we tested the hypothesis that statins act directly on sensory
      neurons to decrease expression of proinflammatory neuropeptides that trigger
      neurogenic inflammation, specifically calcitonin gene-related peptide (CGRP) and
      substance P. Reverse transcriptase-polymerase chain reaction, radioimmunoassay,
      and immunocytochemistry were used to quantify CGRP and substance P expression in
      dorsal root ganglia (DRG) harvested from adult male rats and in primary cultures
      of sensory neurons derived from embryonic rat DRG. Systemic administration of
      statins at pharmacologically relevant doses significantly reduced CGRP and
      substance P levels in DRG in vivo. In cultured sensory neurons, statins blocked
      bone morphogenetic protein (BMP)-induced CGRP and substance P expression and
      decreased expression of these neuropeptides in sensory neurons pretreated with
      BMPs. These effects were concentration-dependent and occurred independent of
      effects on cell survival or axon growth. Statin inhibition of neuropeptide
      expression was reversed by supplementation with mevalonate and cholesterol, but
      not isoprenoid precursors. BMPs signal via Smad activation, and cholesterol
      depletion by statins inhibited Smad1 phosphorylation and nuclear translocation.
      These findings identify a novel action of statins involving down-regulation of
      proinflammatory neuropeptide expression in sensory ganglia via cholesterol
      depletion and decreased Smad1 activation and suggest that statins may be
      effective in attenuating neurogenic inflammation.

PMID- 18079357
TI  - Erythropoietin stimulates cancer cell migration and activates RhoA protein
      through a mitogen-activated protein kinase/extracellular signal-regulated kinase
      dependent mechanism.
AB  - Erythropoietin (Epo) receptor (EpoR) is expressed in several cancer cell lines,
      and the functional consequence of this expression is under extensive study. In
      this study, we used a cervical cancer cell line in which EpoR was first found to
      be expressed and to correlate with the severity of the disease. We demonstrate
      that Epo is a chemoattractant for these cancer cells, enhancing their migration
      under serum-starved conditions. Using a Transwell migration system, we show that
      Epo enhances cancer cell migration in a dose- and time-dependent manner. The
      effect of Epo is dependent on the activity of two signaling pathways: the mitogen
      activated protein kinase (MAPK) pathway and the RhoA GTPase pathway. We show that
      Epo activates both pathways in a Janus kinase-dependent manner and that this
      activation is required for Epo effects on cell migration. Furthermore, we use
      both pharmacological and genetic inhibitors to demonstrate that the activation of
      RhoA GTPase is dependent on the activity of the MAPK pathway, providing the first
      evidence for interaction between these two signaling cascades.

PMID- 18079358
TI  - Flt3L and TK gene therapy eradicate multifocal glioma in a syngeneic glioblastoma
      model.
AB  - The disseminated characteristics of human glioblastoma multiforme (GBM) make it a
      particularly difficult tumor to treat with long-term efficacy. Most preclinical
      models of GBM involve treatment of a single tumor mass. For therapeutic outcomes
      to translate from the preclinical to the clinical setting, induction of an
      antitumor response capable of eliminating multifocal disease is essential. We
      tested the hypothesis that expression of Flt3L (human soluble FMS-like tyrosine
      kinase 3 ligand) and TK (herpes simplex virus type 1-thymidine kinase) within
      brain gliomas would mediate regression of the primary, treated tumor mass and a
      secondary, untreated tumor growing at a distant site from the primary tumor and
      the site of therapeutic vector injection. In both the single-GBM and multifocal
      GBM models used, all saline-treated control animals succumbed to tumors by day
      22. Around 70% of the animals bearing a single GBM mass treated with an
      adenovirus expressing Flt3L (AdFlt3L) and an adenovirus expressing TK (AdTK +
      GCV) survived long term. Approximately 50% of animals bearing a large primary GBM
      that were implanted with a second GBM in the contralateral hemisphere at the same
      time the primary tumors were being treated with AdFlt3L and AdTK also survived
      long term. A second multifocal GBM model, in which bilateral GBMs were implanted
      simultaneously and only the right tumor mass was treated with AdFlt3L and AdTK,
      also demonstrated long-term survival. While no significant difference in survival
      was found between unifocal and multifocal GBM-bearing animals treated with
      AdFlt3L and AdTK, both treatments were statistically different from the saline
      treated control group (p < 0.05). Our results demonstrate that combination
      therapy with AdFlt3L and AdTK can eradicate multifocal brain tumor disease in a
      syngeneic, intracranial GBM model.

PMID- 18079359
TI  - Acoustic neuromas following childhood radiation treatment for benign conditions
      of the head and neck.
AB  - Childhood radiation exposure has been associated with an increased risk for
      developing several neoplasms, particularly benign and malignant thyroid tumors,
      but little is known about the risk of developing acoustic neuromas. The aim of
      this study was to confirm whether there is a risk for acoustic neuromas and, if
      so, to determine its magnitude and duration. We investigated the time trend and
      dose-response relationships for acoustic neuroma incidence in a cohort of 3,112
      individuals who were irradiated as children between 1939 and 1962. Most of the
      patients were treated to reduce the size of their tonsils and adenoids and
      received substantial radiation exposure to the cerebellopontine angle, the site
      of acoustic neuromas. Forty-three patients developed benign acoustic neuromas,
      forty of them surgically resected, far in excess of what might be expected from
      data derived from brain tumor registries. The mean dose (+/-SD) to the
      cerebellopontine angle was 4.6 +/- 1.9 Gy. The relative risk per Gy was 1.14 (95%
      confidence interval 1.0-1.3). The earliest case occurred 20.4 years after
      exposure and the latest 55 years after exposure (mean 38.3 +/- 10.1 years). Our
      study provides support for an association between acoustic neuromas and childhood
      radiation exposure. Although acoustic neuromas are usually benign and often
      asymptomatic, many cause significant morbidity. Following childhood radiation
      exposure, they appear after a long latency and continue to occur many decades
      afterward. Any symptoms of an acoustic neuroma in a patient with a history of
      radiation to the head and neck area should be investigated carefully, and the
      threshold for employing imaging should be lowered.

PMID- 18079360
TI  - Immunological responses in a patient with glioblastoma multiforme treated with
      sequential courses of temozolomide and immunotherapy: case study.
AB  - Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the
      benefits of active antitumor immunization. Temozolomide is an effective
      chemotherapeutic agent for patients with glioblastoma multiforme, but it induces
      significant lymphopenia. Although there is monthly fluctuation of the white blood
      cell count, specifically the CD4 and CD8 counts, there was no cumulative decline
      in the patient described in this case report. Depriving patients of this agent,
      in order to treat with immunotherapy, is controversial. Despite conventional
      dogma, we demonstrated that chemotherapy and immunotherapy can be delivered
      concurrently without negating the effects of immunotherapy. In fact, the
      temozolomide-induced lymphopenia may prove to be synergistic with a peptide
      vaccine secondary to inhibition of regulatory T cells or their delayed recovery.

PMID- 18079362
TI  - A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or
      recurrent CD30+ hematologic malignancies.
AB  - Phase 1 testing of SGN-30, a chimeric monoclonal antibody for the treatment of
      CD30(+) malignancies, was conducted in a multicenter study. To explore the safety
      profile and establish the maximum tolerated dose (MTD), 24 patients with
      refractory or relapsed Hodgkin lymphoma or CD30(+) non-Hodgkin lymphoma received
      6 weekly doses of intravenous SGN-30 at 4 dose levels (2, 4, 8, or 12 mg/kg).
      Serum concentrations of SGN-30 rose rapidly and were dose dependent. Adverse
      events were mild, with nausea, fatigue, and fever attributed to study treatment.
      One episode of hypersensitivity rash was reported. The MTD was not reached.
      Serious adverse events included herpes zoster (n = 2), influenza, and pneumonia.
      One patient with cutaneous anaplastic large cell lymphoma (8 mg/kg) achieved a
      complete response. Six patients, of whom 4 had Hodgkin lymphoma, achieved stable
      disease with durations ranging from 6 to 16 months. The pharmacokinetic profile
      of SGN-30 showed a biphasic disposition, and estimated half-lives ranging between
      1 to 3 weeks. The 6 weekly infusions of SGN-30 resulted in approximately 2- to 3
      fold accumulation in serum exposures consistently across the dose range. These
      results demonstrate that weekly administration of SGN-30 is safe and has modest
      clinical activity in patients with CD30(+) tumors. This trial is registered at
      http://www.ClinicalTrials.gov as no. NCT00051597.

PMID- 18079363
TI  - Modulation of human multidrug resistance protein (MRP) 1 (ABCC1) and MRP2 (ABCC2)
      transport activities by endogenous and exogenous glutathione-conjugated catechol
      metabolites.
AB  - Members of the multidrug resistance protein (MRP/ABCC) subfamily of ATP-binding
      cassette proteins transport a wide array of anionic compounds, including sulfate,
      glucuronide, and glutathione (GSH) conjugates. The present study tested the ATP
      dependent vesicular transport of leukotriene C(4) and 17beta-estradiol 17-(beta-d
      glucuronide) (E(2)17betaG) mediated by the MRP1 and MRP2 transporters in the
      presence of six potential modulators from three different classes of GSH
      conjugated catechol metabolites: the ecstasy metabolite 5-(glutathion-S-yl)-N
      methyl-alpha-methyldopamine (5-GS-N-Me-alpha-MeDA), the caffeic acid metabolite 2
      (glutathion-S-yl)-caffeic acid (2-GS-CA), and four GSH conjugates of 2-hydroxy
      (OH) and 4-OH estrogens (GS estrogens). MRP1-mediated E(2)17betaG transport was
      inhibited in a competitive manner with a relative order of potency of GS
      estrogens (IC(50) <1 microM) > 2-GS-CA (IC(50) 3 microM) > 5-GS-N-Me-alpha-MeDA
      (IC(50) 31 microM). MRP2-mediated transport was inhibited with a similar order of
      potency, except the 2-hydroxy-4-(glutathion-S-yl)-estradiol and 4-hydroxy-2
      (glutathion-S-yl)-estradiol conjugates were approximately 50- and 300-fold less
      potent, respectively. Transport activity was unaffected by N-acetylcysteine
      conjugates of N-Me-alpha-MeDA and CA. The position of GSH conjugation appears
      important as all four GS estrogen conjugates tested were potent inhibitors of
      MRP1 transport, but only the 2-hydroxy-1-(glutathion-S-yl)-estradiol and 2
      hydroxy-1-(glutathion-S-yl)-estrone conjugates were potent inhibitors of MRP2
      mediated transport. In conclusion, we have identified three new classes of MRP1
      and MRP2 modulators and demonstrated that one of these, the estrogen conjugates,
      shows unanticipated differences in their interactions with the two transporters.

PMID- 18079361
TI  - Gene alteration and precursor and mature microRNA transcription changes
      contribute to the miRNA signature of primary effusion lymphoma.
AB  - MicroRNAs are regulated by gene alteration, transcription, and processing. Thus
      far, few studies have simultaneously assessed all 3 levels of regulation. Using
      real-time quantitative polymerase chain reaction (QPCR)-based arrays, we
      determined changes in gene copy number, pre-miRNA, and mature miRNA levels for
      the largest set of primary effusion lymphomas (PELs) to date. We detected PEL
      specific miRNA gene amplifications, and concordant changes in pre-miRNA and
      mature miRNA. We identified 68 PEL-specific miRNAs. This defines the miRNA
      signature of PEL and shows that transcriptional regulation of pre-miRNA as well
      as mature miRNA levels contribute nonredundant information that can be used for
      the classification of human tumors.

PMID- 18079364
TI  - Down-regulation of hepatic cytochrome P450 enzymes in rats with trinitrobenzene
      sulfonic acid-induced colitis.
AB  - Hepatic cytochrome P450 (P450) enzymes are down-regulated during inflammation. In
      this study, an animal model of inflammatory bowel disease was subjected to
      characterization of hepatic P450 expression under inflammatory conditions. Rats
      were treated intracolonically with 100 mg/kg trinitrobenzene sulfonic acid (TNBS)
      dissolved in 30% ethanol, and homogenates of colonic mucosa and hepatic
      microsomes of the rats were prepared. The colitis was accompanied by appearance
      of higher levels of portal endotoxin, interleukin-6, and nitric oxide metabolites
      and decreases in contents and activities for hepatic CYP3A2, CYP2C11, and, to a
      lesser extent, CYP1A2 and CYP2E1. Nimesulide, a preferential COX-2 inhibitor,
      protected rats with TNBS-induced colitis (TNBS-colitis) against the down
      regulation of hepatic CYP3A2. Polymyxin B, which neutralizes endotoxin, curcumin,
      which has anti-inflammatory properties, and gadolinium chloride, which
      inactivates macrophages, attenuated the down-regulation of CYP3A2. Similar
      effects were observed in other P450s such as CYP2C11, but the agents were less
      effective in attenuating the down-regulation. Our data suggest that endogenous
      substances leaked from damaged colon in the rats with TNBS-colitis activate
      Kupffer cells, leading to down-regulation of hepatic P450s with differential
      susceptibility to the inflammatory stimuli. The colitis model, instead of
      exogenous administration of lipopolysaccharide or cytokines, could be applied to
      the study on mechanisms for altered hepatic P450 expression and other liver
      functions under mild inflammatory conditions.

PMID- 18079365
TI  - Probing the carrier capture rate of a single quantum level.
AB  - The performance of many semiconductor quantum-based structures is governed by the
      dynamics of charge carriers between a localized state and a band of electronic
      states. Using scanning tunneling spectroscopy, we studied the transport of
      inelastic tunneling electrons through a prototypical localized state: an isolated
      dangling-bond state on a Si(111) surface. From the saturation of the current at
      an energy resonant with this state, the hole capture rate by the dangling bond
      was determined. By further mapping the spatial extension of its wave function,
      the localized nature of the level was found to be consistent with the small
      magnitude of its cross section. This approach illustrates how the microscopic
      environment of a single defect critically affects its carrier dynamics.

PMID- 18079366
TI  - Assembly mechanism of the contractile ring for cytokinesis by fission yeast.
AB  - Animals and fungi assemble a contractile ring of actin filaments and the motor
      protein myosin to separate into individual daughter cells during cytokinesis. We
      used fluorescence microscopy of live fission yeast cells to observe that membrane
      bound nodes containing myosin were broadly distributed around the cell equator
      and assembled into a contractile ring through stochastic motions, after a
      meshwork of dynamic actin filaments appeared. Analysis of node motions and
      numerical simulations supported a mechanism whereby transient connections are
      established when myosins in one node capture and exert force on actin filaments
      growing from other nodes.

PMID- 18079369
TI  - Year of the Reef.

PMID- 18079368
TI  - Elementary structural motifs in a random network of cytosine adsorbed on a
      gold(111) surface.
AB  - Nonsymmetrical organic molecules adsorbed on solid surfaces may assemble into
      random networks, thereby providing model systems for organic glasses that can be
      directly observed by scanning tunneling microscopy (STM). We investigated the
      structure of a disordered cytosine network on a gold(111) surface created by
      thermal quenching, to temperatures below 150 K, of the two-dimensional fluid
      present on the surface at room temperature. Comparison of STM images to density
      functional theory calculations allowed us to identify three elementary structural
      motifs (zigzag filaments and five- and six-membered rings) that underlie the
      whole supramolecular random network. The identification of elementary structural
      motifs may provide a new framework for understanding medium-range order in
      amorphous and glassy systems.

PMID- 18079367
TI  - The Physcomitrella genome reveals evolutionary insights into the conquest of land
      by plants.
AB  - We report the draft genome sequence of the model moss Physcomitrella patens and
      compare its features with those of flowering plants, from which it is separated
      by more than 400 million years, and unicellular aquatic algae. This comparison
      reveals genomic changes concomitant with the evolutionary movement to land,
      including a general increase in gene family complexity; loss of genes associated
      with aquatic environments (e.g., flagellar arms); acquisition of genes for
      tolerating terrestrial stresses (e.g., variation in temperature and water
      availability); and the development of the auxin and abscisic acid signaling
      pathways for coordinating multicellular growth and dehydration response. The
      Physcomitrella genome provides a resource for phylogenetic inferences about gene
      function and for experimental analysis of plant processes through this plant's
      unique facility for reverse genetics.

PMID- 18079371
TI  - SPACE SCIENCE. China's crystal-sharp moon map sets the Internet abuzz.

PMID- 18079370
TI  - Biomedical research facilities. London's super-lab faces hurdles.

PMID- 18079372
TI  - Climate change. Senate bill would provide billions for deploying cleaner
      technologies.

PMID- 18079373
TI  - Research policy. NIH weighs big changes in peer review.

PMID- 18079374
TI  - Neurobiology. Immune molecules prune synapses in developing brain.

PMID- 18079375
TI  - Physics. Simple scheme stores light by converting it into vibration and back.

PMID- 18079376
TI  - Ecology. Parasites from fish farms driving wild salmon to extinction.

PMID- 18079377
TI  - Reefs in trouble. Spawning for a better life.

PMID- 18079378
TI  - Reefs in trouble. Moonlight sonata on the reef.

PMID- 18079379
TI  - Reefs in trouble. Whiter shades of pale.

PMID- 18079380
TI  - Reefs in trouble. Life on the mean reefs.

PMID- 18079381
TI  - The Gonzonaut goes to Mars.

PMID- 18079382
TI  - Switch to corn promotes Amazon deforestation.

PMID- 18079383
TI  - NASA funding slow, not steady, after space race.

PMID- 18079384
TI  - Memory suppression in PTSD treatment?

PMID- 18079385
TI  - Comment on "Tumor growth need not be driven by rare cancer stem cells".
AB  - Kelly et al. (Brevia, 20 July 2007, p. 337) questioned xenotransplant experiments
      supporting the cancer stem cell (CSC) hypothesis because they found a high
      frequency of leukemia-initiating cells (L-IC) in some transgenic mouse models.
      However, the CSC hypothesis depends on prospective purification of cells with
      tumor-initiating capacity, irrespective of frequency. Moreover, we found similar
      L-IC frequencies in genetically comparable leukemias using syngeneic or
      xenogeneic models.

PMID- 18079386
TI  - Public health. Implementation science.

PMID- 18079387
TI  - Atmospheric science. Resolving an atmospheric enigma.

PMID- 18079388
TI  - Microbiology. A fifth pathway of carbon fixation.

PMID- 18079389
TI  - Ecology. Invasion of the whiteflies.

PMID- 18079390
TI  - Geology. On the accumulation of mud.

PMID- 18079391
TI  - Transcription. Seven ups the code.

PMID- 18079392
TI  - Coral reefs under rapid climate change and ocean acidification.
AB  - Atmospheric carbon dioxide concentration is expected to exceed 500 parts per
      million and global temperatures to rise by at least 2 degrees C by 2050 to 2100,
      values that significantly exceed those of at least the past 420,000 years during
      which most extant marine organisms evolved. Under conditions expected in the 21st
      century, global warming and ocean acidification will compromise carbonate
      accretion, with corals becoming increasingly rare on reef systems. The result
      will be less diverse reef communities and carbonate reef structures that fail to
      be maintained. Climate change also exacerbates local stresses from declining
      water quality and overexploitation of key species, driving reefs increasingly
      toward the tipping point for functional collapse. This review presents future
      scenarios for coral reefs that predict increasingly serious consequences for reef
      associated fisheries, tourism, coastal protection, and people. As the
      International Year of the Reef 2008 begins, scaled-up management intervention and
      decisive action on global emissions are required if the loss of coral-dominated
      ecosystems is to be avoided.

PMID- 18079393
TI  - Carnivorous fungi from Cretaceous amber.
AB  - Carnivorous fungi dating back to the age of the dinosaurs have been found
      fossilized in circa-100-million-year-old amber. The fossil fungi used hyphal
      rings as trapping devices and are preserved together with their prey, small
      nematodes. The excellent preservation in amber allowed comparison with extant
      groups: On the basis of the mode of ring formation and the dimorphic mode of
      life, the fossils cannot be assigned to any recent carnivorous fungus, providing
      evidence that different groups occupied this ecological niche in the Cretaceous
      and that trapping devices were developed independently multiple times in the
      course of Earth history.

PMID- 18079394
TI  - The structure of a human p110alpha/p85alpha complex elucidates the effects of
      oncogenic PI3Kalpha mutations.
AB  - PIK3CA, one of the two most frequently mutated oncogenes in human tumors, codes
      for p110alpha, the catalytic subunit of a phosphatidylinositol 3-kinase, isoform
      alpha (PI3Kalpha, p110alpha/p85). Here, we report a 3.0 angstrom resolution
      structure of a complex between p110alpha and a polypeptide containing the
      p110alpha-binding domains of p85alpha, a protein required for its enzymatic
      activity. The structure shows that many of the mutations occur at residues lying
      at the interfaces between p110alpha and p85alpha or between the kinase domain of
      p110alpha and other domains within the catalytic subunit. Disruptions of these
      interactions are likely to affect the regulation of kinase activity by p85 or the
      catalytic activity of the enzyme, respectively. In addition to providing new
      insights about the structure of PI3Kalpha, these results suggest specific
      mechanisms for the effect of oncogenic mutations in p110alpha and p85alpha.

PMID- 18079395
TI  - Stored light in an optical fiber via stimulated Brillouin scattering.
AB  - We describe a method for storing sequences of optical data pulses by converting
      them into long-lived acoustic excitations in an optical fiber through the process
      of stimulated Brillouin scattering. These stored pulses can be retrieved later,
      after a time interval limited by the lifetime of the acoustic excitation. In the
      experiment reported here, smooth 2-nanosecond-long pulses are stored for up to 12
      nanoseconds with good readout efficiency: 29% at 4-nanosecond storage time and 2%
      at 12 nanoseconds. This method thus can potentially store data packets that are
      many bits long. It can be implemented at any wavelength where the fiber is
      transparent and can be incorporated into existing telecommunication networks
      because it operates using only commercially available components at room
      temperature.

PMID- 18079396
TI  - Mott transition in VO2 revealed by infrared spectroscopy and nano-imaging.
AB  - Electrons in correlated insulators are prevented from conducting by Coulomb
      repulsion between them. When an insulator-to-metal transition is induced in a
      correlated insulator by doping or heating, the resulting conducting state can be
      radically different from that characterized by free electrons in conventional
      metals. We report on the electronic properties of a prototypical correlated
      insulator vanadium dioxide in which the metallic state can be induced by
      increasing temperature. Scanning near-field infrared microscopy allows us to
      directly image nanoscale metallic puddles that appear at the onset of the
      insulator-to-metal transition. In combination with far-field infrared
      spectroscopy, the data reveal the Mott transition with divergent quasi-particle
      mass in the metallic puddles. The experimental approach used sets the stage for
      investigations of charge dynamics on the nanoscale in other inhomogeneous
      correlated electron systems.

PMID- 18079397
TI  - Activity of CeOx and TiOx nanoparticles grown on Au(111) in the water-gas shift
      reaction.
AB  - The high performance of Au-CeO2 and Au-TiO2 catalysts in the water-gas shift
      (WGS) reaction (H2O + CO-->H2 + CO2) relies heavily on the direct participation
      of the oxide in the catalytic process. Although clean Au(111) is not
      catalytically active for the WGS, gold surfaces that are 20 to 30% covered by
      ceria or titania nanoparticles have activities comparable to those of good WGS
      catalysts such as Cu(111) or Cu(100). In TiO(2-x)/Au(111) and CeO(2-x)/Au(111),
      water dissociates on O vacancies of the oxide nanoparticles, CO adsorbs on Au
      sites located nearby, and subsequent reaction steps take place at the metal-oxide
      interface. In these inverse catalysts, the moderate chemical activity of bulk
      gold is coupled to that of a more reactive oxide.

PMID- 18079398
TI  - Accretion of mudstone beds from migrating floccule ripples.
AB  - Mudstones make up the majority of the geological record. However, it is difficult
      to reconstruct the complex processes of mud deposition in the laboratory, such as
      the clumping of particles into floccules. Using flume experiments, we have
      investigated the bedload transport and deposition of clay floccules and find that
      this occurs at flow velocities that transport and deposit sand. Deposition-prone
      floccules form over a wide range of experimental conditions, which suggests an
      underlying universal process. Floccule ripples develop into low-angle foresets
      and mud beds that appear laminated after postdepositional compaction, but the
      layers retain signs of floccule ripple bedding that would be detectable in the
      rock record. Because mudstones were long thought to record low-energy conditions
      of offshore and deeper water environments, our results call for reevaluation of
      published interpretations of ancient mudstone successions and derived
      paleoceanographic conditions.

PMID- 18079399
TI  - A Madden-Julian oscillation event realistically simulated by a global cloud
      resolving model.
AB  - A Madden-Julian Oscillation (MJO) is a massive weather event consisting of deep
      convection coupled with atmospheric circulation, moving slowly eastward over the
      Indian and Pacific Oceans. Despite its enormous influence on many weather and
      climate systems worldwide, it has proven very difficult to simulate an MJO
      because of assumptions about cumulus clouds in global meteorological models.
      Using a model that allows direct coupling of the atmospheric circulation and
      clouds, we successfully simulated the slow eastward migration of an MJO event.
      Topography, the zonal sea surface temperature gradient, and interplay between
      eastward- and westward-propagating signals controlled the timing of the eastward
      transition of the convective center. Our results demonstrate the potential making
      of month-long MJO predictions when global cloud-resolving models with realistic
      initial conditions are used.

PMID- 18079400
TI  - Deep ocean impact of a Madden-Julian oscillation observed by Argo floats.
AB  - Using the new Argo array of profiling floats that gives unprecedented space-time
      coverage of the upper 2000 meters of the global ocean, we present definitive
      evidence of a deep tropical ocean component of the Madden-Julian Oscillation
      (MJO). The surface wind stress anomalies associated with the MJO force eastward
      propagating oceanic equatorial Kelvin waves that extend downward to 1500 meters.
      The amplitude of the deep ocean anomalies is up to six times the amplitude of the
      observed annual cycle. This deep ocean sink of energy input from the wind is
      potentially important for understanding phenomena such as El Nino-Southern
      Oscillation and for interpreting deep ocean measurements made from ships.

PMID- 18079401
TI  - Declining wild salmon populations in relation to parasites from farm salmon.
AB  - Rather than benefiting wild fish, industrial aquaculture may contribute to
      declines in ocean fisheries and ecosystems. Farm salmon are commonly infected
      with salmon lice (Lepeophtheirus salmonis), which are native ectoparasitic
      copepods. We show that recurrent louse infestations of wild juvenile pink salmon
      (Oncorhynchus gorbuscha), all associated with salmon farms, have depressed wild
      pink salmon populations and placed them on a trajectory toward rapid local
      extinction. The louse-induced mortality of pink salmon is commonly over 80% and
      exceeds previous fishing mortality. If outbreaks continue, then local extinction
      is certain, and a 99% collapse in pink salmon population abundance is expected in
      four salmon generations. These results suggest that salmon farms can cause
      parasite outbreaks that erode the capacity of a coastal ecosystem to support wild
      salmon populations.

PMID- 18079402
TI  - Habitat split and the global decline of amphibians.
AB  - The worldwide decline in amphibians has been attributed to several causes,
      especially habitat loss and disease. We identified a further factor, namely
      "habitat split"-defined as human-induced disconnection between habitats used by
      different life history stages of a species-which forces forest-associated
      amphibians with aquatic larvae to make risky breeding migrations between suitable
      aquatic and terrestrial habitats. In the Brazilian Atlantic Forest, we found that
      habitat split negatively affects the richness of species with aquatic larvae but
      not the richness of species with terrestrial development (the latter can complete
      their life cycle inside forest remnants). This mechanism helps to explain why
      species with aquatic larvae have the highest incidence of population decline.
      These findings reinforce the need for the conservation and restoration of
      riparian vegetation.

PMID- 18079403
TI  - Serine-7 of the RNA polymerase II CTD is specifically required for snRNA gene
      expression.
AB  - RNA polymerase II (Pol II) transcribes genes that encode proteins and noncoding
      small nuclear RNAs (snRNAs). The carboxyl-terminal repeat domain (CTD) of the
      largest subunit of mammalian RNA Pol II, comprising tandem repeats of the
      heptapeptide consensus Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7, is required for
      expression of both gene types. We show that mutation of serine-7 to alanine
      causes a specific defect in snRNA gene expression. We also present evidence that
      phosphorylation of serine-7 facilitates interaction with the snRNA gene-specific
      Integrator complex. These findings assign a biological function to this amino
      acid and highlight a gene type-specific requirement for a residue within the CTD
      heptapeptide, supporting the existence of a CTD code.

PMID- 18079404
TI  - Transcribing RNA polymerase II is phosphorylated at CTD residue serine-7.
AB  - RNA polymerase II is distinguished by its large carboxyl-terminal repeat domain
      (CTD), composed of repeats of the consensus heptapeptide Tyr1-Ser2-Pro3-Thr4-Ser5
      Pro6-Ser7. Differential phosphorylation of serine-2 and serine-5 at the 5' and 3'
      regions of genes appears to coordinate the localization of transcription and RNA
      processing factors to the elongating polymerase complex. Using monoclonal
      antibodies, we reveal serine-7 phosphorylation on transcribed genes. This
      position does not appear to be phosphorylated in CTDs of less than 20 consensus
      repeats. The position of repeats where serine-7 is substituted influenced the
      appearance of distinct phosphorylated forms, suggesting functional differences
      between CTD regions. Our results indicate that restriction of serine-7 epitopes
      to the Linker-proximal region limits CTD phosphorylation patterns and is a
      requirement for optimal gene expression.

PMID- 18079405
TI  - A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation
      pathway in Archaea.
AB  - The assimilation of carbon dioxide (CO2) into organic material is quantitatively
      the most important biosynthetic process. We discovered that an autotrophic member
      of the archaeal order Sulfolobales, Metallosphaera sedula, fixed CO2 with acetyl
      coenzyme A (acetyl-CoA)/propionyl-CoA carboxylase as the key carboxylating
      enzyme. In this system, one acetyl-CoA and two bicarbonate molecules were
      reductively converted via 3-hydroxypropionate to succinyl-CoA. This intermediate
      was reduced to 4-hydroxybutyrate and converted into two acetyl-CoA molecules via
      4-hydroxybutyryl-CoA dehydratase. The key genes of this pathway were found not
      only in Metallosphaera but also in Sulfolobus, Archaeoglobus, and Cenarchaeum
      species. Moreover, the Global Ocean Sampling database contains half as many 4
      hydroxybutyryl-CoA dehydratase sequences as compared with those found for another
      key photosynthetic CO2-fixing enzyme, ribulose-1,5-bisphosphate carboxylase
      oxygenase. This indicates the importance of this enzyme in global carbon cycling.

PMID- 18079406
TI  - CX3CR1 deficiency impairs dendritic cell accumulation in arterial intima and
      reduces atherosclerotic burden.
AB  - OBJECTIVE: Dendritic cells (DCs) have recently been found in atherosclerosis
      predisposed regions of arteries and have been proposed to be causal in
      atherosclerosis. The chemokine receptor CX3CR1 is associated with arterial injury
      and atherosclerosis. We sought to determine whether a link exists between
      arterial DC accumulation, CX3CR1, and atherosclerosis. METHODS AND RESULTS: Mouse
      aortas were isolated and subjected to en face immunofluorescence analysis. We
      found that DCs were located predominantly in the intimal regions of arterial
      branch points and curvatures. Consistent with the increased accumulation of
      intimal DCs in aged and ApoE-/- aortas compared with young WT aortas (P=0.004 and
      0.05, respectively), the incidence of atherosclerosis was 88.9% for aged WT and
      100% for ApoE-/- mice compared with 0% for young WT mice. CX3CR1 was expressed on
      intimal DCs and DC numbers were decreased in CX3CR1-deficient aortas of young,
      aged, and ApoE-/- mice (P=0.0008, 0.013, and 0.0099). The reduced DC accumulation
      in CX3CR1-deficiency was also correlated with decreased atherosclerosis in these
      animals. CONCLUSIONS: The accumulation of intimal DC increases in aged and ApoE-/
      aortas and correlates with the generation of atherosclerosis. CX3CR1-deficiency
      impairs the accumulation of DC in the aortic wall and markedly reduces the
      atherosclerotic burden.

PMID- 18079407
TI  - The molecular basis of VEGFR-1 signal transduction pathways in primary human
      monocytes.
AB  - OBJECTIVE: Arteriogenesis, the growth of preexisting arterioles into functional
      arteries, is dependent on the proper function of monocytes. Likewise, wound
      healing is monocyte-dependent. The activation of vascular endothelial growth
      factor receptor-1 (VEGFR-1) in monocytes induces a chemotactic response, triggers
      the expression of tissue factor, and gene expression of cytokines and chemokines.
      Little is known about intracellular signaling pathways mediating the biological
      functions triggered by VEGFR-1 in primary monocytes. METHODS AND RESULTS:
      Monocytes were isolated from peripheral venous blood of young healthy individuals
      using indirect magnetic labeling. Stimulation of monocytes with either vascular
      endothelial growth factor-A (VEGF-A) or placenta growth factor (PlGF-1) triggered
      VEGFR-1 autophosphorylation and phosphorylation of distinct downstream proteins:
      phosphatidylinositol-3 kinase (PI-3K), Akt, p38, and extracellular signal
      regulated kinase-1/2 (ERK1/2). PI-3K appears to be a central regulator in VEGFR-1
      signaling in monocytes as the activation of Akt, p38, and ERK1/2 are PI-3-K
      dependent. In addition, Akt activation functions downstream of p38 kinase. VEGFR
      1-mediated chemotaxis of monocytes is dependent on the activation of PI-3K, p38
      kinase, Akt, and ERK1/2, when assessed in a modified Boyden chamber. CONCLUSIONS:
      Both PlGF-1 and VEGF-A can activate VEGFR-1-dependent signaling pathways in
      primary human monocytes, leading to the activation of several intracellular
      signaling pathways. These pathways are critically involved in primary monocyte
      chemotaxis.

PMID- 18079408
TI  - Activated mast cells induce endothelial cell apoptosis by a combined action of
      chymase and tumor necrosis factor-alpha.
AB  - OBJECTIVE: Activated mast cells (MCs) induce endothelial cell (EC) apoptosis in
      vitro and are present at sites of plaque erosions in vivo. To further elucidate
      the role of MCs in endothelial apoptosis and consequently in plaque erosion, we
      have studied the molecular mechanisms involved in MC-induced EC apoptosis.
      METHODS AND RESULTS: Primary cultures of rat cardiac microvascular ECs (RCMECs)
      and human coronary artery ECs (HCAECs) were treated either with rat MC releasate
      (ie, mediators released on MC activation), rat chymase and tumor necrosis factor
      alpha (TNF-alpha), or with human chymase and TNF-alpha, respectively. MC
      releasate induced RCMEC apoptosis by inactivating the focal adhesion kinase (FAK)
      and Akt-dependent survival signaling pathway, and apoptosis was partially
      inhibited by chymase and TNF-alpha inhibitors. Chymase avidly degraded both
      vitronectin (VN) and fibronectin (FN) produced by the cultured RCMECs. In
      addition, MC releasate inhibited the activation of NF-kappaB (p65) and activated
      caspase-8 and -9. Moreover, in HCAECs, human chymase and TNF-alpha induced
      additive levels of apoptosis. CONCLUSIONS: Activated MCs induce EC apoptosis by
      multiple mechanisms: chymase inactivates the FAK-mediated cell survival
      signaling, and TNF-alpha triggers apoptosis. Thus, by inducing EC apoptosis, MCs
      may contribute to plaque erosion and complications of atherosclerosis.

PMID- 18079410
TI  - Osteopontin expression is required for myofibroblast differentiation.
AB  - Osteopontin (OPN) is a multifunctional cytokine that is strongly expressed in
      healing wounds and fibrotic lesions, both of which are characterized by the
      formation of myofibroblasts. We examined the role of OPN in myofibroblast
      differentiation induced by the profibrotic cytokine transforming growth factor
      beta1. In cultured cardiac or dermal fibroblasts treated with transforming growth
      factor-beta1, there was a 2- to 5-fold increase in the expression of the
      myofibroblast markers alpha-smooth muscle actin and extradomain A fibronectin but
      no significant increase of these proteins in OPN-null fibroblasts. Phalloidin
      staining for actin filaments and immunostaining for alpha-smooth muscle actin and
      focal adhesion proteins showed reduced stress fibers, focal adhesions, and
      lamellipodia in OPN-null fibroblasts compared with wild-type cells. OPN-null
      fibroblasts exhibited 40% to 60% less spreading, 50% less resistance to
      detachment by shear force, and a approximately 3-fold reduction in collagen gel
      contraction. These defects were partially rescued by ectopic expression of OPN.
      Mass spectrometric analysis of proteins in focal adhesions formed on collagen
      type I beads revealed an enrichment of HMGB1 protein in wild-type cells, whereas
      HMGB1 was not detected in OPN-null cells. Treatment of wild-type cells with small
      interfering RNA to knock down OPN reduced transforming growth factor-beta1
      induced alpha-smooth muscle actin and HMGB1 to levels observed in OPN-null cells.
      These studies demonstrate that OPN is required for the differentiation and
      activity of myofibroblasts formed in response to the profibrotic cytokine
      transforming growth factor-beta1.

PMID- 18079409
TI  - Smooth muscle protein 22alpha-mediated patchy deletion of Bmpr1a impairs cardiac
      contractility but protects against pulmonary vascular remodeling.
AB  - Vascular expression of bone morphogenetic type IA receptor (Bmpr1a) is reduced in
      lungs of patients with pulmonary arterial hypertension, but the significance of
      this observation is poorly understood. To elucidate the role of Bmpr1a in the
      vascular pathology of pulmonary arterial hypertension and associated right
      ventricular (RV) dysfunction, we deleted Bmpr1a in vascular smooth muscle cells
      and in cardiac myocytes in mice using the SM22alpha;TRE-Cre/LoxP;R26R system. The
      LacZ distribution reflected patchy deletion of Bmpr1a in the lung vessels, aorta,
      and heart of SM22alpha;TRE-Cre;R26R;Bmpr1a(flox/+) and flox/flox mutants. This
      reduction in BMPR-IA expression was confirmed by Western immunoblot and
      immunohistochemistry in the flox/flox group. This did not affect pulmonary
      vasoreactivity to acute hypoxia (10% O2) or the increase in RV systolic pressure
      and RV hypertrophy following 3 weeks in chronic hypoxia. However, both
      SM22alpha;TRE-Cre;R26R;Bmpr1a(flox/+) and flox/flox mutant mice had fewer
      muscularized distal pulmonary arteries and attenuated loss of peripheral
      pulmonary arteries compared with age-matched control littermates in hypoxia. When
      Bmpr1a expression was reduced by short interference RNA in cultured pulmonary
      arterial smooth muscle cells, serum-induced proliferation was attenuated
      explaining decreased hypoxia-mediated muscularization of distal vessels. When
      Bmpr1a was reduced in cultured microvascular pericytes by short interference RNA,
      resistance to apoptosis was observed and this could account for protection
      against hypoxia-mediated vessel loss. The similar elevation in RV systolic
      pressure and RV hypertrophy, despite the attenuated remodeling with chronic
      hypoxia in the flox/flox mutants versus controls, was not a function of elevated
      left ventricular end diastolic pressure but was associated with increased
      periadventitial deposition of elastin and collagen, potentially influencing
      vascular stiffness.

PMID- 18079411
TI  - Remodeling of T-tubules and reduced synchrony of Ca2+ release in myocytes from
      chronically ischemic myocardium.
AB  - In ventricular cardiac myocytes, T-tubule density is an important determinant of
      the synchrony of sarcoplasmic reticulum (SR) Ca2+ release and could be involved
      in the reduced SR Ca2+ release in ischemic cardiomyopathy. We therefore
      investigated T-tubule density and properties of SR Ca2+ release in pigs, 6 weeks
      after inducing severe stenosis of the circumflex coronary artery (91+/-3%, N=13)
      with myocardial infarction (8.8+/-2.0% of total left ventricular mass). Severe
      dysfunction in the infarct and adjacent myocardium was documented by magnetic
      resonance and Doppler myocardial velocity imaging. Myocytes isolated from the
      adjacent myocardium were compared with myocytes from the same region in weight
      matched control pigs. T-tubule density quantified from the di-8-ANEPPS (di-8
      butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate) sarcolemmal staining
      was decreased by 27+/-7% (P<0.05). Synchrony of SR Ca2+ release (confocal line
      scan images during whole-cell voltage clamp) was reduced in myocardium myocytes.
      Delayed release (ie, half-maximal [Ca2+]i occurring later than 20 ms) occurred at
      35.5+/-6.4% of the scan line in myocardial infarction versus 22.7+/-2.5% in
      control pigs (P<0.05), prolonging the time to peak of the line-averaged [Ca2+]i
      transient (121+/-9 versus 102+/-5 ms in control pigs, P<0.05). Delayed release
      colocalized with regions of T-tubule rarefaction and could not be suppressed by
      activation of protein kinase A. The whole-cell averaged [Ca2+]i transient
      amplitude was reduced, whereas L-type Ca2+ current density was unchanged and SR
      content was increased, indicating a reduction in the gain of Ca2+-induced Ca2+
      release. In conclusion, reduced T-tubule density during ischemic remodeling is
      associated with reduced synchrony of Ca2+ release and reduced efficiency of
      coupling Ca2+ influx to Ca2+ release.

PMID- 18079412
TI  - Protein carbonylation as a novel mechanism in redox signaling.
AB  - Reactive oxygen species serve as second messengers for signal transduction;
      however, molecular targets of oxidant signaling have not been defined. Here, we
      show that ligand-receptor-mediated signaling promotes reactive oxygen species
      dependent protein carbonylation. Treatment of pulmonary artery smooth muscle
      cells with endothelin-1 increased protein carbonyls. Carbonylation of the
      majority of proteins occurred transiently, suggesting that there is also a
      mechanism for decarbonylation induced by endothelin-1. Decarbonylation was
      suppressed by inhibition of thioredoxin reductase, and cellular thioredoxin was
      upregulated during the decarbonylation phase. These results indicate that
      endothelin-1 promotes oxidant signaling as well as thioredoxin-mediated reductive
      signaling to regulate carbonylation and decarbonylation mechanisms. In cells
      treated with endothelin receptor antagonists, hydrogen peroxide scavengers, or an
      iron chelator, we identified, via mass spectrometry, proteins that are
      carbonylated in a receptor- and Fenton reaction-dependent manner, including
      annexin A1, which promotes apoptosis and suppresses cell growth. Carbonylation of
      annexin A1 by endothelin-1 was followed by proteasome-dependent degradation of
      this protein. We propose that carbonylation and subsequent degradation of annexin
      A1 may play a role in endothelin-mediated cell growth and survival, important
      events in pulmonary vascular remodeling. Protein carbonylation in response to
      ligand-receptor interactions represents a novel mechanism in redox signaling.

PMID- 18079414
TI  - Aging and numerosity estimation.
AB  - In two experiments, young and older participants were asked to find the
      approximate number of dots in collections including between 40 and 460 dots.
      Experiment 1 showed that both age groups had comparable performance and no age
      related differences in the power-function exponents for numerosity. Experiment 2
      found that these age-related similarities were not due to speed-accuracy trade
      offs or to compensation by older adults for potential age-related decline in
      numerosity estimation processes. Furthermore, young and older participants'
      estimation performance was influenced by physical features of stimuli only for
      very large numerosities, presumably because these are poorly represented in long
      term memory. Implications of these findings for the further understanding of how
      participants accomplish numerosity estimation tasks and effects of aging in this
      domain are discussed.

PMID- 18079413
TI  - Mutation of the HEXIM1 gene results in defects during heart and vascular
      development partly through downregulation of vascular endothelial growth factor.
AB  - Our previous studies and those of others indicated that the transcription factor
      Hexamethylene-bis-acetamide-inducible protein 1 (HEXIM1) is a tumor suppressor
      and cyclin-dependent kinase inhibitor, and that these HEXIM1 functions are mainly
      dependent on its C-terminal region. We provide evidence here that the HEXIM1 C
      terminal region is critical for cardiovascular development. HEXIM1 protein was
      detected in the heart during critical time periods in cardiac growth and chamber
      maturation. We created mice carrying an insertional mutation in the HEXIM1 gene
      that disrupted its C-terminal region and found that this resulted in prenatal
      lethality. Heart defects in HEXIM1(1 to 312) mice included abnormal coronary
      patterning and thin ventricular walls. The thin myocardium can be partly
      attributed to increased apoptosis. Platelet endothelial cell adhesion molecular
      precursor-1 staining of HEXIM1(1 to 312) heart sections revealed decreased
      vascularization of the myocardium despite the presence of coronary vasculature in
      the epicardium. The expression of vascular endothelial growth factor (VEGF),
      known to affect angioblast invasion and myocardial proliferation and survival,
      was decreased in HEXIM1(1 to 312) mice compared with control littermates. We also
      observed decreased fibroblast growth factor 9 (FGF9) expression, suggesting that
      effects of HEXIM1 in the myocardium are partly mediated through epicardial FGF9
      signaling. Together our results suggest that HEXIM1 plays critical roles in
      coronary vessel development and myocardial growth. The basis for this role of
      HEXIM1 is that VEGF is a direct transcriptional target of HEXIM1, and involves
      attenuation a repressive effects of C/EBPalpha on VEGF gene transcription.

PMID- 18079415
TI  - Living with chronic health conditions: age differences in affective well-being.
AB  - The current study examined age differences in affective well-being and reactivity
      to daily stressors among people varying in health status. Participants (N =
      3,493), aged 25 to 74 years, reported global affective well-being in the Midlife
      Development in the United States survey, and a subset (n = 983) reported their
      affective reactivity to stressors across eight consecutive evenings in the
      National Study of Daily Experiences. Across groups of people varying in number of
      chronic conditions, older adults reported higher levels of global affective well
      being and lower levels of affective reactivity than did younger adults, with one
      exception. Among people reporting four or more chronic conditions, older adults
      were just as reactive to daily stressors as were younger adults.

PMID- 18079416
TI  - Social network types among older adults: a multidimensional approach.
AB  - Theories of social relations suggest that individuals' personal networks reflect
      multiple aspects of relationships, and that different constellations are more or
      less supportive of well-being. Using data from the Berlin Aging Study (N = 516;
      age, M = 85 years), we derived network types that reflect information about
      structure, function, and quality, and we examined their association with well
      being. A cluster analysis revealed six network types: diverse-supported, family
      focused, friend focused-supported, friend focused-unsupported, restricted
      nonfriends-unsatisfied, and restricted-nonfamily-unsupported. Well-being was
      predicted differentially by the six types. Although the oldest-old individuals
      (85 years of age or older) were overrepresented in the friend-focused-supported
      and restricted types, age did not moderate the association of types with well
      being. A holistic consideration of structure, function, and quality of social
      networks in old age offers unique insights.

PMID- 18079417
TI  - It's never too late to engage in lifestyle activities: significant concurrent but
      not change relationships between lifestyle activities and cognitive speed.
AB  - Little is known about potential longitudinal relationships between participation
      in social, physical, and intellectual activities and later cognitive performance.
      Data from the Victoria Longitudinal Study (n = 530) were used to test whether
      baseline and change in lifestyle engagement were related to corresponding
      indicators of cognitive speed (measured by mean-level and intraindividual
      variability). Regressions based on random effects model estimates showed that
      cross-sectional activity participation predicted corresponding values of both
      mean-level and intraindividual variability, but few longitudinal relationships
      were significant. Overall, a higher frequency of participation in cognitively
      complex activities was related to faster response times and lower intraindividual
      variability. Findings suggest that activity level at one point in time may be a
      more important predictor of cognition than an individual's changes in activity
      level.

PMID- 18079418
TI  - Aging and lexical inhibition: the effect of orthographic neighborhood frequency
      in young and older adults.
AB  - The aim of this study was to examine whether the lexical inhibition underlying
      orthographic neighborhood effects in visual word recognition is changed with
      aging. To do so, orthographic neighborhood frequency was manipulated for French
      words that had either no higher frequency neighbor (e.g., taupe), or at least one
      higher frequency neighbor (e.g., the word loupe has two higher frequency
      neighbors, coupe and soupe). Young adults (mean age = 20.9 years) and older
      adults (mean age = 67.8 years) performed a standard lexical decision task. An
      interaction was found between age group and orthographic neighborhood frequency
      on word latencies. More precisely, an inhibitory effect of neighborhood frequency
      was observed for the young adults but not for the older ones. These data are
      consistent with the assumption of an age-related decline in lexical inhibition
      and activation. The findings are discussed in the framework of visual word
      recognition and aging.

PMID- 18079419
TI  - Personality traits, education, and health-related quality of life among older
      adult primary care patients.
AB  - Both lower education and the personality trait of neuroticism have been
      associated with lower health-related quality of life (HRQOL) among older adults,
      but little is known about the role of other personality traits in HRQOL. We
      examined the associations of all Five-Factor Model personality traits and
      education, above and beyond physician-rated medical burden, with different
      aspects of HRQOL in a sample of 442 primary care patients 65 years of age or
      older who completed the NEO Five-Factor Inventory. We used the Medical Outcomes
      Survey Short Form-36 (SF-36), instrumental activities of daily living (IADLs),
      and the physical self-maintenance scale to assess different aspects of HRQOL.
      Even after statistically adjusting for age, gender, the presence of major
      depressive disorder, and physician-rated medical morbidity, we found that a
      higher neuroticism level was associated with lower functioning on the IADLs and
      the physical self-maintenance scale and worse HRQOL on the Social Functioning and
      Role Emotional subscales of the SF-36. Higher conscientiousness level was
      associated with better HRQOL on the SF-36 Role Physical scale and better IADL
      function. Higher education level was associated with better HRQOL on all measures
      except emotional role impairment. In exploratory moderation analyses, a higher
      openness level diminished the effect of medical burden on IADL impairment.
      Preliminary population-attributable risk comparisons suggest that--on a strictly
      population basis--the impairment conferred by a neuroticism level that is 1 SD
      above the mean may be equivalent to or greater than that of major depressive
      disorder. Future research aimed at understanding how personality traits are
      linked with HRQOL and functioning in later life may enhance the identification of
      at-risk older adults and inform the development of interventions.

PMID- 18079420
TI  - The power of personality in discriminating between healthy aging and early-stage
      Alzheimer's disease.
AB  - This study examined differences in personality in the earliest stages of dementia
      of the Alzheimer type (DAT) relative to healthy aging, and the power of
      personality in discriminating healthy aging from early-stage DAT. Four groups of
      participants (middle-aged controls, older controls, persons with very mild DAT,
      and persons with mild DAT) and their families were administered Costa and
      McCrae's NEO Five-Factor Inventory. On the basis of both self-report and
      informant report, there was an increase in neuroticism and a decrease in
      conscientiousness in persons with very mild DAT relative to healthy individuals
      without it, and in persons with mild DAT relative to those with very mild DAT.
      Moreover, informant reports of neuroticism and conscientiousness capture
      substantial unique variance in discriminating healthy aging and very mild DAT,
      above and beyond standard neuropsychological tests. Discussion focuses on the
      importance of personality traits as a noncognitive indicator of early-stage DAT.

PMID- 18079421
TI  - Cultural differences in the relationship between aging and the correspondence
      bias.
AB  - Previous work suggests that older adults show a stronger correspondence bias than
      do young adults. In the present study we examine whether age differences in the
      correspondence bias are universal or if they differ across cultures. A sample of
      young and older adults from China completed an attitude-attribution paradigm. We
      compared these data with an existing American data set. We found cultural
      differences in the extremity of the ratings. Chinese participants reported less
      extreme attitude ratings than did the participants in our American sample.
      Furthermore, we found cultural differences in the correspondence bias only in the
      older adult samples, with older Americans displaying a greater bias than older
      Chinese. We discuss our findings from a life-span developmental perspective as
      well as from an acculturation perspective.

PMID- 18079423
TI  - Reliability and validity of the Older Americans Resources and Services (OARS)
      social resources scale in six European countries.
AB  - OBJECTIVES: The purpose of this article is to examine data quality, reliability,
      and construct validity of the Older Americans Resources and Services social
      resources scale in six European countries (The Netherlands, Luxembourg, Italy,
      Austria, the United Kingdom, and Sweden). METHODS: A questionnaire was
      administered through face-to-face interviews in five countries, and postal
      interview in the sixth, to representative populations of adults aged 50 to 90
      living independently (N = 12,478). This article examines missing values and
      distribution of items in the social resources scale, and consistency of skew and
      kurtosis across countries. We performed item-total correlations and ran
      confirmatory factor analyses to test a three-factor model obtained in previous
      U.S. and Spanish analyses. Cronbach's alpha determined the reliability of the
      factors. RESULTS: We observed a relatively large proportion of missing data for
      one item (have someone who would help you). All items correlated with a score
      equal to or greater than 0.20. Although the confirmatory factor analyses
      generally supported the acceptability of the three-factor structure in the
      European data, the reliability of two dimensions (dependability and affective)
      was unacceptably low. DISCUSSION: Differences across countries make it unlikely
      that researchers can develop a single social resources scale that would have item
      equivalence in multiple countries.

PMID- 18079422
TI  - Positive and negative social exchanges and disability in later life: an
      investigation of trajectories of change.
AB  - OBJECTIVES: Various aspects of one's social ties are thought to influence the
      onset, progression, and course of disability in older adulthood. Although the
      longitudinal course of social ties and physical disability is likely to be marked
      by fluctuations over time and intraindividual variation, few studies have
      explored how patterns of change in positive and negative social exchanges relate
      to patterns of change in disability across time. The current study, therefore,
      examined the extent to which distinct longitudinal trajectories of positive and
      negative exchanges were associated with patterns of physical disability. METHODS:
      We followed a sample of 482 community-dwelling older adults with little to no
      disability at baseline for 2 years. RESULTS: Results identified multiple,
      distinct trajectory groups for positive and negative exchanges and disability.
      Latent class growth analyses revealed that individuals with chronically high or
      low positive exchanges were likely to experience low and increasing levels of
      disability. With respect to negative exchanges, individuals with moderately
      increasing negative exchanges showed patterns of increasing disability and
      disability remission, whereas chronically low or absent negative exchanges were
      associated with low and increasing levels of disability. DISCUSSION: Findings
      highlight the importance of evaluating multiple trajectories of change in older
      adults' social exchanges and disability.

PMID- 18079424
TI  - Once validated, always validated?

PMID- 18079425
TI  - Characteristics of strong commitments to intergenerational family care of older
      adults.
AB  - OBJECTIVE: The purpose of this research was to describe the characteristics of
      strong commitment to home-based elder care among intergenerational family
      caregivers. METHODS: I conducted two qualitative studies using in-depth
      interviews with primary and secondary intergenerational caregivers. A total of 45
      primary caregivers, 10 spouses, and 11 adult grandchildren discussed development
      of their relative's care, their caregiving experiences, use of paid services, and
      how caregiving affected their lives. I followed McCracken's five-step method for
      analysis of long interviews. RESULT: Strongly committed caregivers composed half
      of the total sample. All primary caregivers with strong commitments were women;
      some strongly committed secondary caregivers were men. Strong commitments had
      moral, religious, and affectionate bases. Participants gave compassionate care
      and reframed adverse situations as manageable challenges. Family members and paid
      providers assisted primary caregivers. Participants viewed caregiving as
      rewarding and as an opportunity to teach compassion to children. DISCUSSION:
      Results suggest that strongly committed intergenerational caregivers need support
      from both family and formal care services to sustain their commitments to care.
      Future research can investigate the role of resilience in caregiver commitments
      and develop caregiver commitment measures for use in elaborating models of
      informal long-term care.

PMID- 18079426
TI  - Regional differences in mother adult-child relations: a brief report.
AB  - OBJECTIVE: In the past decade, there has been increasing interest in regional
      differences in attitudes and behaviors; however, little of this research has
      focused on families, particularly in later life. The goal of this article is to
      address two specific questions: (a) Does adult children's closeness and contact
      with mothers vary by region? and (b) Can traditionalism explain patterns of
      regionality? METHODS: To address these questions, we used a subsample of adult
      children (aged 25-74) from the National Survey of Families and Households (Wave
      II) who were asked about contact and closeness with their mothers (aged 65 and
      older). RESULT: Adult children residing in the South reported greater contact and
      closeness with mothers than those residing in other parts of the country.
      Traditionalism regarding gender ideology and religious involvement could not
      account for the greater contact and closeness observed among Southern
      respondents. DISCUSSION: Recent literature has demonstrated the persistence of a
      distinctive Southern culture; the present study contributes to this body of work
      by showing that intergenerational cohesion is also greater in the South than in
      other regions of the United States. These findings call for greater attention to
      regionality in future studies of intergenerational relations.

PMID- 18079427
TI  - The lived experience of depression in elderly African American women.
AB  - OBJECTIVE: This article focuses on the lived experience of depression in 20
      elderly African American women. METHODS: Data on depression emerged from research
      that qualitatively explored experiences of depression, sadness, and suffering in
      120 community-dwelling persons aged 80 and older, stratified by gender,
      ethnicity, and self-reported health. RESULT: We placed women's narratives under
      three general themes: Depression was (a) linked with diminishment of personal
      strength, (b) related to sadness and suffering, and (c) preventable or resolvable
      through personal responsibility. Brief accounts illustrate how themes emerged in
      women's discussion of depression. DISCUSSION: African American women created a
      language for depression that was rooted in their personal and cultural history
      and presented in vivid vignettes through their life stories. Their belief systems
      and the language they used to describe depression are integral aspects of the
      lived experience of depression.

PMID- 18079428
TI  - Employment and occupation effects on depressive symptoms in older Americans: does
      working past age 65 protect against depression?
AB  - OBJECTIVES: This article examines the effects of work status, occupational
      sector, and occupation type on depressive symptoms in older Americans. We
      partially controlled for the healthy worker selection effect by including
      disability as a predictor of both work status and depressive symptoms. METHODS:
      We analyzed a nationally representative sample of 23,247 respondents aged 65 to
      88 from the National Health Interview Survey pooled over 1997 to 2000. We used
      structural equation models with latent variables to assess relationships between
      work/occupation and depressive symptoms. RESULTS: Older Americans who work had
      lower levels of depressive symptoms as compared to older nonworkers. Membership
      in several worker groups, generally higher status occupations, protected against
      depressive symptoms. After controlling for disability, the difference in level of
      depressive symptoms for workers versus nonworkers did not persist. However,
      workers in specific occupational sectors and types reported different levels of
      depressive symptoms even when we controlled for disability. DISCUSSION: The
      mental health benefit of working, among persons aged 65 and older, may be due to
      the healthy worker effect. However, the particular job sector in which older
      workers are employed matters. Socioeconomic status and financial versus personal
      motivations for working are potentially important explanations for differences.

PMID- 18079429
TI  - The continuing benefits of education: adult education and midlife cognitive
      ability in the British 1946 birth cohort.
AB  - OBJECTIVE: Evidence shows education positively impacts cognitive ability.
      However, researchers have given little attention to the potential impact of adult
      education on cognitive ability, still malleable in midlife. The primary study aim
      was to examine whether there were continuing effects of education over the life
      course on midlife cognitive ability. METHODS: This study used data from the
      Medical Research Council National Survey of Health and Development, also known as
      the British 1946 birth cohort, and multivariate regression to estimate the
      continuing effects of adult education on multiple measures of midlife cognitive
      ability. RESULT: Educational attainment completed by early adulthood was
      associated with all measures of cognitive ability in late midlife. The continued
      effect of education was apparent in the associations between adult education and
      higher verbal ability, verbal memory, and verbal fluency in late midlife. We
      found no association between adult education and mental speed and concentration.
      DISCUSSION: Associations between adult education and midlife cognitive ability
      indicate wider benefits of education to health that may be important for social
      integration, well-being, and the delay of cognitive decline in later life.

PMID- 18079430
TI  - Perceptions of body weight among older adults: analyses of the intersection of
      gender, race, and socioeconomic status.
AB  - OBJECTIVES: We examine the effects of gender, race, and socioeconomic status
      (SES) on perceptions of body weight among older adults and the role of status
      based differences in BMI in these processes. METHODS: Data are derived from face
      to-face interviews with 1,164 adults aged 65 years and older in the District of
      Columbia and two counties in Maryland in 2000-2001. RESULTS: With "perceived
      appropriate weight" as the comparison group, multinomial logistic regression
      analyses indicate that white adults, women, and high-SES individuals are more
      likely than black adults, men, and low-SES individuals to describe themselves as
      overweight or obese. However, these disparities are observed only after
      statistically adjusting for race, gender, and SES disparities in BMI. Moreover,
      the positive effect of SES on the likelihood of reporting overweight or obese
      perceptions is strongest among black women. Among low SES individuals, white
      women are more likely than men and black women to describe themselves as obese
      (relative to the "perceived appropriate weight" category). DISCUSSION: Our
      observations underscore the importance of taking SES contingencies into account
      when exploring race-gender differences in perceived body weight. This study
      further contributes to the literature by documenting the important suppression
      patterns associated with race, gender, and SES differences in BMI.

PMID- 18079431
TI  - Preventive effects of perioperative parecoxib on post-discectomy pain.
AB  - BACKGROUND: Cyclooxygenase inhibitor treatment is viewed increasingly critical
      because of safety considerations, and there are several open questions on their
      optimal use. METHODS: In a randomized placebo-controlled study in 320 patients
      undergoing discectomy, we administered parecoxib 40 mg either perioperatively
      (before operation and after operation), after operation (first dose given in the
      evening after surgery), or before operation (single parecoxib dose given 45 min
      before surgery). We measured the main outcome variables: average pain score,
      morphine consumption, and opioid-related symptom distress at 25, 49, and 73 h
      after surgery. RESULTS: Perioperative parecoxib significantly (i) improved the
      pain score compared with both placebo and postoperative parecoxib, (ii) decreased
      morphine consumption, and (iii) reduced the opioid-related symptom distress
      score. Neither a single preoperative dose nor postoperative parecoxib (first dose
      given in the evening after surgery) significantly improved morphine's analgesic
      effectiveness. CONCLUSIONS: Perioperative parecoxib compared with postoperative
      parecoxib improves post-discectomy pain and results in a reduction in adverse
      effects associated with opioid therapy. Postoperative parecoxib, or a single pre
      incisional parecoxib dose, does not significantly improve post-discectomy pain or
      opioid side-effects up to 3 days after surgery.

PMID- 18079432
TI  - Repopulating activity of ex vivo-expanded murine hematopoietic stem cells resides
      in the CD48-c-Kit+Sca-1+lineage marker- cell population.
AB  - A better understanding of the biology of cultured hematopoietic stem cells (HSCs)
      is required to achieve ex vivo expansion of HSCs. In this study, clonal analysis
      of the surface phenotype and repopulating activity of ex vivo-expanded murine
      HSCs was performed. After 7 days of culture with stem cell factor,
      thrombopoietin, fibroblast growth factor-1, and insulin-like growth factor-2,
      single CD34-/lowc-Kit+Sca-1+lineage marker- (CD34-KSL) cells gave rise to various
      numbers of cells. The proportion of KSL cells decreased with increasing number of
      expanded cells. Transplantation studies revealed that the progeny containing a
      higher percentage of KSL cells tended to have enhanced repopulating potential. We
      also found that CD48 was heterogeneously expressed in the KSL cell population
      after culture. Repopulating activity resided only in the CD48-KSL cell
      population, which had a relatively long intermitotic interval. Microarray
      analysis showed surprisingly few differences in gene expression between cultured
      CD48-KSL cells (cycling HSCs) and CD48+KSL cells (cycling non-HSCs) compared with
      freshly isolated CD34-KSL cells (quiescent HSCs), suggesting that the maintenance
      of stem cell activity is controlled by a relatively small number of genes. These
      findings should lead to a better understanding of ex vivo-expanded HSCs.

PMID- 18079433
TI  - Human dental pulp stem cells improve left ventricular function, induce
      angiogenesis, and reduce infarct size in rats with acute myocardial infarction.
AB  - Human dental pulp contains precursor cells termed dental pulp stem cells (DPSC)
      that show self-renewal and multilineage differentiation and also secrete multiple
      proangiogenic and antiapoptotic factors. To examine whether these cells could
      have therapeutic potential in the repair of myocardial infarction (MI), DPSC were
      infected with a retrovirus encoding the green fluorescent protein (GFP) and
      expanded ex vivo. Seven days after induction of myocardial infarction by coronary
      artery ligation, 1.5 x 10(6) GFP-DPSC were injected intramyocardially in nude
      rats. At 4 weeks, cell-treated animals showed an improvement in cardiac function,
      observed by percentage changes in anterior wall thickening left ventricular
      fractional area change, in parallel with a reduction in infarct size. No
      histologic evidence was seen of GFP+ endothelial cells, smooth muscle cells, or
      cardiac muscle cells within the infarct. However, angiogenesis was increased
      relative to control-treated animals. Taken together, these data suggest that DPSC
      could provide a novel alternative cell population for cardiac repair, at least in
      the setting of acute MI.

PMID- 18079434
TI  - Expression of multiple chondroitin/dermatan sulfotransferases in the neurogenic
      regions of the embryonic and adult central nervous system implies that complex
      chondroitin sulfates have a role in neural stem cell maintenance.
AB  - Chondroitin/dermatan sulfotransferases (C/D-STs) underlie the synthesis of
      diverse sulfated structures in chondroitin/dermatan sulfate (CS/DS) chains.
      Recent reports have suggested that particular sulfated structures on CS/DS
      polymers are involved in the regulation of neural stem cell proliferation. Here,
      we examined the gene expression profile of C/D-STs in the neurogenic regions of
      embryonic and adult mouse central nervous system. Using reverse transcription
      polymerase chain reaction analysis, all presently known C/D-STs were detected in
      the dorsal and ventral telencephalon of the embryonic day 13 (E13) mouse embryo,
      with the exception of chondroitin 4-O-sulfotransferase (C4ST)-3. In situ
      hybridization for C4ST-1, dermatan 4-O-sulfotransferase-1, chondroitin 6-O
      sulfotransferase (C6ST)-1 and -2, and uronosyl 2-O-sulfotransferase revealed a
      cellular expression of these sulfotransferase genes in the embryonic germinal
      zones of the forebrain. The expression of multiple C/D-STs is maintained on cells
      residing in the adult neural stem cell niche. Neural stem cells cultured as
      neurospheres maintained the expression of these enzymes. Consistent with the gene
      expression pattern of C/D-STs, disaccharide analysis revealed that neurospheres
      and E13 mouse brain cells synthesized CS/DS chains containing monosulfated, but
      also significant amounts of disulfated, disaccharide units. Functionally, the
      inhibition of sulfation with sodium chlorate resulted in a significant, dose
      dependent decrease in neurosphere number that could not be rescued by the
      addition of individual purified glycosaminoglycan (GAG) chains, including
      heparin. These findings argue against a simple charge-based mechanism of GAG
      chains in neural stem cell maintenance. The synergistic activities of C/D-STs
      might allow for the adaptive modification of CS/DS proteoglycans with diversely
      sulfated CS/DS chains in the extracellular microenvironment that surrounds neural
      stem cells.

PMID- 18079435
TI  - Overexpression of vascular endothelial growth factor 189 in breast cancer cells
      leads to delayed tumor uptake with dilated intratumoral vessels.
AB  - Vascular endothelial growth factor (VEGF) is essential for breast cancer
      progression and is a relevant target in anti-angiogenesis. Although VEGF121 and
      VEGF165, the fully or partially secreted isoforms, respectively, have been the
      focus of intense studies, the role of the cell-associated VEGF189 isoform is not
      understood. To clarify the contribution of VEGF189 to human mammary
      carcinogenesis, we established several clones of MDA-MB-231 cells stably
      overexpressing VEGF189 (V189) and VEGF165 (V165). V189 and V165 clones increased
      tumor growth and angiogenesis in vivo. Remarkably, V165 induced the most rapid
      tumor uptake, whereas V189 increased vasodilation. In vitro overexpression of
      VEGF165 and VEGF189 increases the proliferation and chemokinesis of these cancer
      cells. Interestingly, overexpression of VEGF189 increased cell adhesion on
      fibronectin (1.9-fold) and vitronectin (1.6-fold), as compared to VEGF165,
      through alpha5beta1 and alphavbeta5 integrins. Using the BIACore system we
      demonstrated for the first time that VEGF189 binds directly to neuropilin-1,
      which is strongly expressed in MDA-MB-231 cells. In contrast, VEGF-R2 was not
      significantly expressed and VEGF-R1 was expressed at low level. Our in vitro
      results suggest an autocrine effect of VEGF189 on breast cancer cells, probably
      through neuropilin-1. In conclusion, our data indicate that VEGF189 participates
      in mammary tumor growth through both angiogenesis and nonangiogenic functions.
      Whether VEGF189 overexpression is correlated to prognosis in human breast tumors
      remains to be established.

PMID- 18079436
TI  - Analysis of tau phosphorylation and truncation in a mouse model of human
      tauopathy.
AB  - Recent evidence has suggested that truncation of tau protein at the caspase
      cleavage site D421 precedes hyperphosphorylation and may be necessary for the
      assembly of tau into filaments in Alzheimer's disease and other tauopathies. Here
      we have investigated the time course of the appearance of phosphorylated and
      truncated tau in the brain and spinal cord of mice transgenic for mutant human
      P301S tau protein. This mouse line recapitulates the essential molecular and
      cellular features of the human tauopathies, including tau hyperphosphorylation,
      tau filament formation, and neurodegeneration. Soluble tau was strongly
      phosphorylated at 1 to 6 months of age. Low levels of phosphorylated, sarkosyl
      insoluble tau were detected at 2 months, with a steady increase up to 6 months of
      age. Tau truncated at D421 was detected at low levels in Tris-soluble and
      detergent-soluble tau at 3 to 6 months of age. By immunoblotting, it was not
      detected in sarkosyl-insoluble tau. However, by immunoelectron microscopy, a
      small percentage of tau in filaments from brain and spinal cord of transgenic
      mice was truncated at D421. Similar findings were obtained using dispersed
      filaments from Alzheimer's disease and FTDP-17 brains. The late appearance and
      low abundance of tau ending at D421 indicate that it is unlikely that truncation
      at this site is necessary for the assembly of tau into filaments.

PMID- 18079437
TI  - Significance of tumor-associated stroma in promotion of intratumoral
      lymphangiogenesis: pivotal role of a hyaluronan-rich tumor microenvironment.
AB  - Stromal cells, together with extracellular matrix components, provide a tumor
      microenvironment that is pivotal for cancer cell growth and progression. In our
      previous study using a conditional transgenic mouse model of breast cancer, the
      overproduction of hyaluronan, a major extracellular constituent, accelerated
      tumor angiogenesis through stromal cell recruitment. This finding led us to
      investigate the role of hyaluronan in the lymphatic vessel system. Here, we have
      found that microenvironmental hyaluronan promoted tumor lymphangiogenesis
      concurrently with the formation of stromal structures. Additionally, lymphatic
      vessels frequently penetrated and accumulated into stromal compartments, and up
      regulation of vascular endothelial growth factor-C and -D was detected at tumor
      stromal interfaces. To assess the contribution of stromal cells to
      lymphangiogenesis in vivo, we established tumor-associated fibroblasts from
      hyaluronan-overproducing mammary tumors and implanted them together with
      carcinoma cells from control tumors or MCF-7 human breast carcinoma cells in nude
      mice. Carcinoma cells grew rapidly in association with marked stromal reactions
      and lymphangiogenesis. Without the stromal cells, however, the tumors developed
      slowly with less stroma and lymphatic vessels. These findings underline the
      significance of tumor-associated stroma in the promotion of intratumoral
      lymphangiogenesis and suggest a pivotal role for the hyaluronan-rich tumor
      microenvironment.

PMID- 18079438
TI  - Role of nicotinic and estrogen signaling during experimental acute and chronic
      bladder inflammation.
AB  - Inflammation is a physiological process that characterizes many bladder diseases.
      We hypothesized that nicotinic and estrogen signaling could down-regulate bladder
      inflammation. Cyclophosphamide was used to induce acute and chronic bladder
      inflammation. Changes in bladder inflammation were measured histologically and by
      inflammatory gene expression. Antagonizing nicotinic signaling with mecamylamine
      further aggravated acute and chronic inflammatory changes resulting from
      cyclophosphamide treatment. Estrogen and nicotinic signaling independently
      attenuated acute bladder inflammation by decreasing neutrophil recruitment and
      down-regulating elevated lipocalin-2 and cathepsin D expression. However, the
      combined signaling by the estrogen and nicotinic pathways, as measured by
      macrophage infiltration and up-regulation of interleukin-6 expression in the
      bladder, synergistically reduced chronic bladder inflammation. The elevated
      expression of p65 nuclear localization in bladders treated with cyclophosphamide
      or cyclophosphamide with mecamylamine suggested nuclear factor-kappa B activation
      in the chronic inflammatory process. The complementary treatment of 17 beta
      estradiol and the nicotinic agonist anabasine resulted in the translocation of
      p65 to the cytoplasm, again greater than either alone. Activation of nuclear
      factor-kappaB can result in macrophage activation and/or elevation in epithelial
      proliferation. These data suggest that 17 beta-estradiol and anabasine reduce
      chronic bladder inflammation through reduction of nuclear translocation of p65 to
      suppress cytokine expression.

PMID- 18079439
TI  - Nitric oxide regulates neutrophil migration through microparticle formation.
AB  - The role of nitric oxide (NO) in regulating neutrophil migration has been
      investigated. Human neutrophil migration to interleukin (IL)-8 (1 nmol/L) was
      measured after a 1-hour incubation using a 96-well chemotaxis plate assay. The NO
      synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME) significantly (P <
      0.001) enhanced IL-8-induced migration by up to 45%. Anti-CD18 significantly (P <
      0.001) inhibited both IL-8-induced and L-NAME enhanced migration. Antibodies to L
      selectin or PSGL-1 had no effect on IL-8-induced migration but prevented the
      increased migration to IL-8 induced by L-NAME. L-NAME induced generation of
      neutrophil-derived microparticles that was significantly (P < 0.01) greater than
      untreated neutrophils or D-NAME. This microparticle formation was dependent on
      calpain activity and superoxide production. Only microparticles from L-NAME and
      not untreated or D-NAME-treated neutrophils induced a significant (P < 0.01)
      increase in IL-8-induced migration and transendothelial migration. Pretreatment
      of microparticles with antibodies to L-selectin (DREG-200) or PSGL-1 (PL-1)
      significantly (P < 0.001) inhibited this effect. The ability of L-NAME-induced
      microparticles to enhance migration was found to be dependent on the number of
      microparticles produced and not an increase in microparticle surface L-selectin
      or PSGL-1 expression. These data show that NO can modulate neutrophil migration
      by regulating microparticle formation.

PMID- 18079440
TI  - Mechanisms and consequences of neutrophil interaction with the endothelium.
AB  - Leukocyte recruitment into inflamed tissue proceeds in a cascade-like fashion.
      The first contact of neutrophils with the endothelium is mediated by selectins
      and their counterreceptors, followed by rolling of neutrophils along the
      endothelial wall of postcapillary venules and integrin-mediated arrest. While
      rolling, neutrophils collect different inflammatory signals that can activate
      several pathways. In addition to activation of neutrophils by ligation of G
      protein-coupled receptors with chemokines and other chemoattractants, integrins
      and selectin ligands are also able to signal into the cell, where they initiate
      neutrophil extravasation, promote cytoskeletal rearrangement, and ultimately
      induce superoxide production and degranulation. These signaling pathways may be
      targeted by therapeutic interventions to inhibit specific functions of
      neutrophils without affecting others. This Review is focused on the signaling
      events during the interaction of neutrophils with the endothelium.

PMID- 18079441
TI  - Mechanism of glycosaminoglycan-mediated bone and joint disease: implications for
      the mucopolysaccharidoses and other connective tissue diseases.
AB  - We have previously shown that glycosaminoglycan (GAG) storage in animal models of
      the mucopolysaccharidoses (MPS) leads to inflammation and apoptosis within
      cartilage. We have now extended these findings to synovial tissue and further
      explored the mechanism underlying GAG-mediated disease. Analysis of MPS rats,
      cats, and/or dogs revealed that MPS synovial fibroblasts and fluid displayed
      elevated expression of numerous inflammatory molecules, including several
      proteins important for lipopolysaccharide signaling (eg, Toll-like receptor 4 and
      lipoprotein-binding protein). The expression of tumor necrosis factor, in
      particular, was elevated up to 50-fold, leading to up-regulation of the
      osteoclast survival factor, receptor activator of nuclear factor-kappaB ligand,
      and the appearance of multinucleated osteoclast-like cells in the MPS bone
      marrow. Treatment of normal synovial fibroblasts with GAGs also led to production
      of the prosurvival lipid sphingosine-1-phosphate, resulting in enhanced cell
      proliferation, consistent with the hyperplastic synovial tissue observed in MPS
      patients. In contrast, GAG treatment of normal chondrocytes led to production of
      the proapoptotic lipid ceramide, confirming the enhanced cell death we had
      previously observed in MPS cartilage. These findings have important implications
      for the pathogenesis and treatment of MPS and have further defined the mechanism
      of GAG-stimulated disease.

PMID- 18079442
TI  - The peer-review process.

PMID- 18079443
TI  - Space use according to the distribution of resources and level of competition.
AB  - The manner in which an animal moves throughout and utilizes the space available
      to it depends on the dispersal, availability, and level of competition for
      resources the animal requires for its biological functioning. We tested groups of
      broilers (Gallus gallus domesticus) in 3 experimental group sizes of 5, 10, and
      20 individuals per group under 3 resource distribution patterns. Groups were
      tested with access to 1 large single feeder, 2 medium-sized feeders, or 4 small
      feeders. In all arrangements the total amount of food available per bird remained
      constant. During the first phase groups had free access to all available feeders,
      and in the second phase access at each feeder was restricted to a single bird.
      Space use, measured by calculating core areas and interindividual distances
      between group members, increased as group size grew larger and as feeders became
      more widely distributed. Not all group sizes responded equally to the resource
      distribution patterns. Space use patterns for the smaller group sizes were more
      strongly affected by resource distribution patterns than the larger group sizes.
      When access to the feeders was restricted, consumption, aggression, and space use
      increased. Broilers adjusted their space use and aggressive behavior according to
      the level of competition, dictated not only by group size but also resource
      distribution and accessibility.

PMID- 18079444
TI  - Economic and welfare benefits of environmental enrichment for broiler breeders.
AB  - Designs to enrich the environment are crucial in the effort to fully address the
      biological needs of domestic animals. Although enrichment programs have been
      shown to improve health and welfare, little is known of their potential for
      application to commercial broiler breeder environments. We investigated the
      potential benefits of cover panels for broiler breeder reproductive performance
      in a commercial setting. This demonstration trial occurred on 5 commercial
      broiler breeder farms, each with a control and panel treatment room containing
      approximately 7,000 females and 800 males. Reproductive performance was measured
      from 25 to 60 wk by the number of eggs laid per female per week as well as weekly
      fertility and hatchability rates. The location of marked males was recorded
      weekly to quantify male movement. Access to cover panels improved egg production
      by 2.1% and maintained better hatchability and fertility throughout the breeding
      cycle (significant interactions of age and panel treatment) leading to an
      additional 4.5 chicks/female. Male home ranges, based on minimum convex polygons,
      were larger in the enriched (259 +/- 24.4 m(2)) vs. control flocks (184 +/- 23.1
      m(2)). Providing enrichment in the form of cover panels improved reproductive
      performance, most likely by increasing males' mating opportunities and reducing
      female stress. We found a clear economic benefit to providing enrichment, an
      estimated $3 million if all breeder houses within the participating company were
      outfitted with the panels. These results demonstrate that environmental
      enrichment is not only beneficial for broiler breeder welfare, but can also be
      economically advantageous, resulting in a win-win situation for poultry welfare
      and production.

PMID- 18079445
TI  - Association of interleukin-10 cluster genes and Salmonella response in the
      chicken.
AB  - Salmonella enteritidis lipopolysaccharide stimulates interleukin 10 (IL10) gene
      expression in chickens. Four genes in the IL10 cluster [polymeric immunoglobulin
      receptor (PIGR), interleukin 10 (IL10), map kinase-activated protein kinase 2
      (MAPKAPK2), and ligatin (LGTN)] plus dual-specificity tyrosine-(Y)
      phosphorylation regulated kinase1A (DYRK1A) were investigated using the F(8)
      generation of 2 related advanced intercross lines (AIL). The AIL were generated
      by crossing outbred broilers with dams of 2 highly inbred lines (Leghorn and
      Fayoumi). Intercrossing continued within the 2 dam lines. The F(8) chicks (n =
      132) were intraesophageally inoculated at 1 d with S. enteritidis. At d 7 or 8,
      both spleen tissue and cecal contents were cultured to quantify S. enteritidis
      load. The F(8) population was genotyped for one single nucleotide polymorphism
      (SNP) per gene by using a multiplexed SNaPshot assay. Association of gene SNP
      with S. enteritidis bacterial burden was analyzed by the GLM. The MAPKAPK2 and
      IL10 genes were highly (P < 0.001) associated with S. enteritidis burden in
      spleen tissue and cecal luminal content. Suggestive associations (P < 0.05) of
      PIGR with spleen tissue and cecal content were found. The results suggest that
      SNP in MAPKAPK2 and IL10 were strongly associated with Salmonella burden and may
      be valuable in generating resistant birds by marker-assisted selection.

PMID- 18079446
TI  - Evaluation of a Lactobacillus-based probiotic culture for the reduction of
      Salmonella enteritidis in neonatal broiler chicks.
AB  - We evaluated the effect of a Lactobacillus-based probiotic culture (FM-B11) for
      reduction of Salmonella Enteritidis in neonatal broiler chicks. In all
      experiments, chicks were challenged with approximately 10(4) cfu of Salmonella
      Enteritidis upon arrival at our laboratory, and the treatments were administered
      1 h postchallenge. Cecal tonsil samples were obtained 24 h posttreatment and
      enriched for Salmonella Enteritidis recovery. The first experiment compared the
      effects of oral administration of doses of 10(4), 10(6), and 10(8) cfu/chick. In
      this experiment, doses of 10(6) and 10(8) both significantly reduced Salmonella
      Enteritidis recovery compared with controls (15 vs. 85% Salmonella Enteritidis
      positive), but 10(4) cfu did not significantly reduce Salmonella Enteritidis
      recovery. The second experiment compared the efficacy of oral administration of
      the live probiotic culture, with or without supernatant removed, to inactivated
      cultures or supernatant alone. Live probiotic organisms, with or without
      supernatant, significantly reduced Salmonella Enteritidis in this experiment, but
      inactivated or cell-free treatments did not reduce Salmonella Enteritidis. In the
      final 2 experiments, differing doses of probiotic culture were administered on
      the vent lips, where the treatment was taken into the lower gastrointestinal
      tract via cloacal drinking. Concentrations of probiotic culture from 10(2) to
      10(7) cfu/chick significantly reduced Salmonella Enteritidis, and there was no
      difference in Salmonella Enteritidis recovery between treatment concentrations.
      These data suggest that this Lactobacillus-based probiotic culture may be
      efficacious for reduction of Salmonella Enteritidis in neonatal chicks.

PMID- 18079447
TI  - Production of hen egg yolk immunoglobulins simultaneously directed against
      Salmonella enteritidis and Salmonella typhimurium in the same egg yolk.
AB  - The present study was an attempt to raise hen egg yolk Ig (IgY) simultaneously
      directed against Salmonella Enteritidis (SE) and Salmonella Typhimurium (ST) in
      the same egg yolk. The immunopotentiating effect of 2 different adjuvants --
      Freund's adjuvants (FA) and immunostimulating complexes matrix (IM) -- on
      antibody response was also evaluated. Bacterial outer membrane proteins (OMP)
      were selected as target antigens. The ISA Brown hens, specific-Salmonella spp.
      free status, divided into 6 groups were intramuscularly injected with a mono
      compound antigen preparation: SE-OMP (treatment SE-FA or SE-IM) or ST-OMP
      (treatment ST-FA or ST-IM), or a combined antigen preparation: (1/2) SE-OMP and
      (1/2) STOMP (treatment SEST-FA or SEST-IM). Titers of antibodies in yolk were
      evaluated biweekly with ELISA. There was no antigen x adjuvant interaction on
      antibody titers. Anti-SE IgY titers in hens that received treatment SEST-FA or
      SEST-IM were statistically similar (P > 0.05) as compared with those obtained
      from hens immunized with treatment SE-FA or SE-IM. Anti-ST IgY titers in hens
      immunized with treatment SEST-FA or SEST-IM were slightly lower than those of
      hens that received treatment ST-FA or ST-IM. The cross-reactivity of anti-SE IgY,
      induced by treatment SE-FA or SE-IM, with ST-OMP antigen and that of anti-ST IgY,
      induced by ST-FA or ST-IM, with SE-OMP antigen were arbitrarily assessed on d 43
      and 155 by ELISA. The average cross-reactivity of anti-SE IgY with ST-OMP antigen
      was 71.7%. The average cross-reactivity of anti-ST IgY with SE-OMP antigen was
      78.8%. In FA groups, antibody titers were found higher (P < 0.05) than those in
      IM groups. Furthermore, no extensive lesions or clinical abnormalities were
      detected in hens injected with FA. These findings showed the opportunity to raise
      IgY antibody against 2 Salmonella serovars in the same yolk and that FA was more
      efficient than IM in mediating antibody response.

PMID- 18079448
TI  - Effect of selection for phagocytosis in dwarf chickens on immune and reproductive
      characters.
AB  - In current study, phagocytosis product (PP) of peripheral blood monocytes was
      detected among 920 dwarf chickens (460 per sex) at 20 wk of age, and based on
      discrepancies of PP, the flock was grouped (the highest group, the medium group,
      and the lowest group). Then serum hemagglutination inhibition antibody titers and
      subpopulations of T-lymphocytes of each group were examined after inoculations of
      avian influenza virus H5N2 inactivated vaccine (20 wk of age), avian influenza
      virus H9 inactivated vaccine (24 wk of age), and Newcastle disease virus-egg drop
      syndrome virus bigeminal inactivated vaccine (28 wk of age), respectively, to
      study the relationship between PP and immune response. To gain insight into
      effects of selection for PP on number of eggs, mean egg weight, fertilization
      rate, hatchability, and rate of healthy chicks, 9 (3 x 3) mating combinations
      were conducted. The results showed that (1) selection for higher PP in both sexes
      benefited to humoral immunity but not CD8(+) T-lymphocyte mediated immunity in
      dwarf chickens; (2) there were effects of selection for higher PP in hens on
      fertilization rate (P < 0.05), hatchability (P < 0.05), rate of healthy chicks (P
      < 0.05), and level of IgY antibody (P < 0.0001); however, hens' PP had no effects
      on number of eggs (P > or = 0.05) or egg weight (P > or = 0.05) and cocks' PP had
      no effect (P > or = 0.05) on any trait mentioned above. The results indicated
      that phagocytosis of peripheral blood monocytes might be an indicator of humoral
      immunity in dwarf chickens; furthermore, selection of hens with higher PP was not
      only beneficial to fertilization rate, but also benefited to hatchability and
      rate of healthy chicks in that the hens had stronger humoral immunity, which
      might contribute to maternal antibody in eggs.

PMID- 18079449
TI  - Arginine and vitamin E modulate the subpopulations of T lymphocytes in broiler
      chickens.
AB  - We examined the effects of vitamin E (VE) and Arg on the subpopulations of T
      lymphocytes in peripheral blood after an infectious bursal disease virus
      vaccination (20 d old, n = 54). Broiler chickens were fed diets with normal
      levels of Arg (NARG, 1.2%) or high levels of Arg (HARG, 2.2%) and 3 levels of VE
      (40, 80, or 200 IU/kg of feed) in a factorial arrangement of treatments. The
      percentages of CD4+ and CD8+ cells 9 d after vaccination were not different in
      birds fed the HARG or NARG feed, but they were higher in birds fed the VE80 diet
      than in birds fed the VE40 diet. Birds fed the VE200 feed had similar levels of
      CD4+ and CD8+ cells as birds fed the VE40 diet. However, 19 d after vaccination,
      the percentage of CD4+ cells was higher in birds fed the HARG (43.93 +/- 1.05)
      diet than in birds fed the NARG diet (41.14 +/- 1.05) and in birds fed the VE80
      and VE200 (44.1 +/- 1.28 and 44.42 +/- 1.28, respectively) diets compared with
      birds fed the VE40 diet (39.04 +/- 1.28). On the other hand, the percentage of
      CD8+ cells was highest in birds fed the HARG-VE80 feed compared with all the
      other Arg and VE combinations. The percentages of CD3+ cells and BU-1+ cells were
      higher in birds fed the HARG (81.35 +/- 1.46 and 22.3 +/- 0.89, respectively)
      diet than in birds fed the NARG diets (77.82 +/- 1.46 and 18.93 +/- 0.89,
      respectively). Birds fed the VE40 had a higher amount of BU-1+ (24.35 +/- 1.073)
      but lower amounts of CD3+ cells (75.76 +/- 1.76) than birds fed the VE80 (18.46
      +/- 1.073 and 81.67 +/- 1.76) and VE200 (19.03 +/- 1.073 and 81.19 +/- 1.76,
      respectively). Neither Arg nor VE had an effect on the CD4+:CD8+ cell ratio and
      on the percentage of immature (CD4+CD8+) T lymphocytes 9 d after vaccination.
      These results suggest that Arg and VE have complimentary effects on cellular and
      humoral immune function and may enhance the resistance of broilers to infectious
      diseases.

PMID- 18079450
TI  - Hematology and enzyme histochemistry of the peripheral blood leucocytes in rock
      partridges (Alectoris graeca).
AB  - The purpose of this study was to determine the percentages of alpha-naphthyl
      acetate esterase (ANAE)-positive and acid phosphatase (ACP)-positive peripheral
      blood lymphocytes (PBL) and the percentages of leukocytes in the rock partridge
      at different ages. Blood samples obtained from the vena basilica of 18 healthy
      rock partridges (Alectoris graeca) at 1 d, 5 wk, and 12 wk of age were used. Mean
      percentages of ANAE-positive PBL for the 3 age groups were 37, 29.83, and 47.83%
      for 1 d, 5 wk, and 12 wk of age, respectively. Heterophils also gave ANAE
      positive reactions. Mean percentages of ACP-positive PBL for the 3 age groups
      were 70, 81, and 86.1% for 1 d, 5 wk, and 12 wk of age, respectively. Although
      monocytes showed a diffuse granular staining pattern, heterophils displayed a
      weak positive reaction for ACP. Thrombocytes showed a small granular staining
      pattern. This study contributes by broadening the hematological research on avian
      species and provides a guideline for identifying blood cells in the rock
      partridge.

PMID- 18079451
TI  - Broiler chick thrombocyte response to lipopolysaccharide.
AB  - The effect of lipopolysaccharide (LPS) on the expression of proinflammatory
      cytokines, interleukin (IL)-1beta, IL-6, and IL-12 in broiler chick thrombocytes
      was investigated. At 4 wk of age, blood samples were collected, and isolated
      thrombocytes were incubated with LPS for 1 h. Ribonucleic acid was extracted from
      the cells to examine the expression of the proinflammatory cytokines using real
      time reverse transcription PCR. It was found that expressions of IL-1beta, IL-6,
      and IL-12 in thrombocytes were unaffected by diets containing corticosterone and
      vitamin C fed to chicks. However, LPS exposure did increase the expressions of
      these cytokines. The fact that thrombocytes are so abundant and can be stimulated
      by LPS makes them primary effector cells in innate host defenses against
      bacterial infections in chickens.

PMID- 18079452
TI  - Utilization of oil by-product from the purification process of conjugated
      linoleic Acid as feeding supplements for the accumulation of conjugated linoleic
      acid in the egg yolk.
AB  - This study was performed to examine an efficient way to use oil by-product which
      is obtained during the purification process of conjugated linoleic acid (CLA)
      from safflower oil. The CLA by-product (CBP) was fed to the laying hens to
      accumulate CLA in the egg yolk. Egg yolk samples from 3 different dietary groups
      were analyzed: control; CBP, 2%; and CLA-80 (which contained 80% free form of
      CLA), 2%. Fatty acids from the yolk were analyzed by gas chromatography, and the
      parameters of egg quality were determined. During the feeding trial, there was
      little alteration in the egg quality and egg production of the tested groups. The
      CLA contents in the test group with CBP, which contain CLA as glyceride form,
      significantly increased in the first week of feeding and had the highest level
      among the tested groups throughout the feeding trials, whereas the CLA group
      showed an increase in CLA contents from the third week. Moreover, the contents of
      total CLA isomers in CLA-80 and CBP oils were decreased by 12.92 and 0.51% after
      heat treatment in 48 h, and the contents of linoleic acid (LA) isomer in LA-80
      (which contained 80% free form of LA) and LA by-product (LBP) oils were decreased
      by 19.63 and 5.78%, respectively. It was confirmed that a major form of fats in
      CBP was mainly esterified forms, whereas the fats in CLA-80 and LA-80 were
      composed of free fatty acids. There was no significant difference in the egg
      quality and production among the tested groups. It is meaningful that the oil by
      product could be utilized as a source for functional foods of animal origin
      without influencing egg quality and production.

PMID- 18079453
TI  - Pasture intake improves the performance and meat sensory attributes of free-range
      broilers.
AB  - Free-range chickens are assumed to consume low to moderate levels of pasture,
      although the effects of forage intake in broiler performance and poultry meat
      quality remain to be established. In addition, despite cellulases and
      hemicellulases being widely used as feed supplements to improve the nutritive
      value of cereal-based diets for fast-growing broilers, the potential interest of
      these biocatalysts in the production of free-range chicken is yet to be
      established. In this study, broilers of the RedBro Cou Nu x RedBro M genotype
      were fed a cereal-based diet in portable floorless pens located either on a
      rainfed subterranean clover (Trifolium subterraneum) pasture or on an irrigated
      white clover (Trifolium repens) pasture. Control birds were maintained at the
      same site in identical pens but with no access to pastures. The importance of
      pasture intake and enzyme supplementation in the performance and meat sensory
      properties of the free-range chicken from d 28 to 56 was investigated. The
      results revealed that although cellulase and hemicellulase supplementation had no
      impact on broiler performance (P > 0.05), birds foraging on legume-based pastures
      reached significantly greater final BW. The data suggest that the improvement in
      broiler performance results from increased intake of the cereal-based feed rather
      than from an improvement in the efficiency of nutrient utilization per se.
      Interestingly, although the intake of the subterranean clover pasture had no
      impact on the tenderness, juiciness, and flavor of broiler meat, members of a 30
      person consumer panel classified the meat from grazing broilers with greater
      scores for overall appreciation. Together, the results suggest that pasture
      intake promotes bird performance while contributing to the production of broiler
      meat with preferred sensory attributes.

PMID- 18079454
TI  - Influence of pasture intake on the fatty acid composition, and cholesterol,
      tocopherols, and tocotrienols content in meat from free-range broilers.
AB  - Over the last centuries, Western diets acquired a dramatic imbalance in the ratio
      of polyunsaturated fatty acids (PUFA) to saturated fatty acids (SFA) with a
      concomitant reduction in the dietary proportion of n-3 PUFA. Pastures are a good
      source of n-3 fatty acids, although the effect of forage intake in the fatty acid
      profile of meat from free-range chicken remains to be evaluated. In addition, it
      is unknown if consumer interest in specialty poultry products derived from free
      range or organic production systems is accompanied by a greater nutritional
      quality of these products. In this study, broilers of the RedBro Cou Nu x RedBro
      M genotype were fed on a cereal-based diet in portable floorless pens located
      either on subterranean clover (Trifolium subterraneum) or white clover (Trifolium
      repens) pastures. Control birds were maintained at the same site in identical
      pens but had no access to pasture. The capacity of ingested forage to modulate
      broiler meat fatty acid profiles and the meat content of total cholesterol,
      tocopherols, and tocotrienols was investigated in broiler chicks slaughtered at d
      56. The results suggested that pasture intake (<5% DM) had a low impact on the
      fatty acid and vitamin E homologue profiles of meat from free-range broilers.
      However, breast meat from birds with free access to pasture presented lower
      levels of the n-6 and n-3 fatty acid precursors linoleic acid (18:2n-6) and alpha
      linolenic acid (18:3n-3), respectively. In spring the levels of eicosapentaenoic
      acid (20:5n-3) in breast meat were significantly greater in birds consuming
      pastures, which suggests greater conversion of alpha-linolenic acid into
      eicosapentaenoic acid in these birds. Finally, when compared with meat from
      slower-growing genotypes obtained under the conventional European free-range
      production systems with slaughtering at d 81, meat from birds of the Ross
      genotype raised intensively and slaughtered at d 35 seemed to have greater
      nutritional quality.

PMID- 18079455
TI  - Daily energy intake of broiler chickens is altered by proximate nutrient content
      and form of the diet.
AB  - An experiment was designed to test the ability of broiler chickens to equalize
      daily energy intake when proximate components of the diet were changed. A
      factorial arrangement was used to test effects of protein, fat, and fiber content
      in the diet. The simplest diet contained only corn and soybean meal to provide
      energy and protein. Protein contents were calculated to be 16.4, 18.2, and 20.0%,
      with added protein from a combination of corn gluten meal, fish meal, and peanut
      meal. Hydrolyzed fat was added at 0, 2.5, 5.0, and 7.5% of the diets. A
      combination of alfalfa meal, oats, and wheat middlings was used to increase the
      fiber of the corn soy diet by approximately 2 and 4%. The 36 combinations were
      fed as mash. In addition, 8 of the diets were fed as pellets. All diets were fed
      for 12 d from the time broilers reached approximately 1.2 kg. A total excreta
      collection was used to determine ME, and carcass analysis provided fat and energy
      content. When fed mash, only sex had a significant effect on grams of feed eaten
      per day. Sex and dietary fat content affected gain per day. Sex, fat, and fiber
      altered the kcal of ME eaten per day. Broilers fed 5% added fat ate approximately
      10% more energy per day than those fed no added fat, and broilers fed 4% added
      fiber ate approximately 20% less ME than those fed no added fiber. A comparison
      of results from mash and pellets showed that only sex and form affected gain per
      day, feed per day, and kilocalories of ME eaten per day. For the mash and
      pellets, protein, fat, fiber, and several interactions affected the ME per gram;
      however, the ME per gram was similar for pellets and mash. The results suggest
      that the diet composition and form have a significant effect on the energy intake
      of broiler chickens.

PMID- 18079456
TI  - A comparison of methods to determine amino acid availability of feedstuffs in
      cecectomized ganders.
AB  - Experiments were conducted to compare endogenous amino acid losses and the true
      amino acid availability (TAAA) of 3 feedstuffs by using methods involving a short
      term fasting and an N-free diet with cecectomized ganders. Diets were formulated
      to contain soybean meal, fish meal, and cottonseed meal as the sole source of
      protein. A precision-fed assay was used in which each feed sample was precise-fed
      (60 g) to geese and excreta were collected for 48 h. A N-free diet and fasting
      methods were used to evaluate the endogenous amino acid losses. Endogenous losses
      of 3 amino acids were significantly different (P < 0.01) with the N-free diet and
      fasting methods. The TAAA of soybean meal, fish meal, and cottonseed meal
      determined by N-free diet method ranged from 84.49 to 97.09%, 89.18 to 98.16%,
      and 77.09 to 98.32%, respectively. The TAAA of these 3 diets determined by the
      fasting method ranged from 83.50 to 97.77%, 88.08 to 99.60%, and 76.09 to 98.09%,
      respectively. However, there were only a few small differences (P > 0.05) between
      methods in each amino acid. In conclusion, there was no difference in
      determination of the amino acid availability of these feedstuffs using
      cecectomized ganders between the N-free diet and fasting methods.

PMID- 18079457
TI  - Metabolizable energy values determined with intact and cecectomized roosters.
AB  - Mature White Leghorn roosters that were intact or cecectomized were used to
      determine the ME of a diet. Seven intact and 7 cecectomized roosters were fasted
      for 3 d, with total excreta collection on d 2 and 3. Approximately 1 wk after
      completion of the trial, the same roosters were force-fed 28 g of a diet that was
      85% corn and 15% soybean meal after a 1-d fast. Excreta were collected from d 2
      and 3 and dried. There was no difference in the energy and nitrogen excreted by
      intact and cecectomized roosters when they were fasted for 3 d. The energy and
      nitrogen excreted by cecectomized roosters were greater than by intact roosters
      when they were fed the test diet. As a result, the AME, TME, AME(n), and TME(n)
      were all larger from intact roosters than from cecectomized roosters. Our results
      suggest that intact roosters should be used to determine the energy content of
      ingredients that will be fed to commercial flocks.

PMID- 18079458
TI  - Nitrogen-corrected apparent metabolizable energy value of crude glycerol for
      laying hens.
AB  - An experiment was conducted with laying hens to determine the AME(n) value of
      crude glycerol, a coproduct of biodiesel production. Crude glycerol (87%
      glycerol, 9% water, 0.03% methanol, 1.26% Na, and 3,625 kcal/kg of gross energy)
      was obtained from a commercial biodiesel production facility (Ag Processing Inc.,
      Sergeant Bluff, IA). A total of forty-eight 40-wk-old laying hens (Hy-Line W-36)
      were placed in metabolic cages (2 hens/ cage) and given free access to the
      experimental diets. A corn and soybean meal-based basal diet (18% CP, 2,875
      kcal/kg of AME(n), 4.51% Ca, 0.51% nonphytate P) was formulated with 15%
      glucose.H(2)O and 1% Celite. Four dietary treatments were created by substituting
      0, 5, 10, or 15% crude glycerol for glucose.H(2)O (3,640 kcal/kg of AME(n)).
      After 7 d of dietary adaptation, excreta were collected twice daily for 3 d,
      freeze-dried, and analyzed for contents of DM, Kjeldahl N, acid-insoluble ash,
      and gross energy. Egg production was recorded daily, and eggs were collected on d
      7 and 8 of the experiment for calculation of egg mass (egg production x egg
      weight). Feed consumption was measured over the 10-d experimental period. Egg
      production data were analyzed by ANOVA with 4 treatments and 6 replications in a
      completely randomized experimental design. The AME(n) value of crude glycerol was
      estimated as the slope of the linear relationship between the inclusion rate of
      dietary crude glycerol and the glucose-corrected AME(n) value of the experimental
      diets. No significant treatment effects (P > 0.1) were apparent for egg
      production rate (93.0%), egg weight (56.1 g), egg mass (52.2 g/d), or feed
      consumption (104 g/d). Linear regression analysis (P < 0.001, r(2) = 0.92, n =
      24) revealed that the AME(n) value of the crude glycerol used in this study was
      3,805 +/- 238 kcal/kg (mean +/- SEM; as-is basis) for laying hens.

PMID- 18079459
TI  - Thiamin phosphates in egg yolk granules and plasma of regular and embryonated
      eggs of hens and in five- and seven-day-old embryos.
AB  - The thiamin (TH), thiamin monophosphate (TMP), thiamin diphosphate (TDP), and
      thiamin triphosphate (TTP) content was analyzed in yolk plasma and yolk granules
      of unincubated and incubated chicken eggs and in 5- and 7-day-old chick embryos.
      Analytes were extracted from samples weighing approximately 1 g, with
      trichloroacetic acid (0.4 g/L), isolated with solid-phase extraction, and
      determined with HPLC. Before solid-phase extraction with a C-18 cartridge and a
      strong anion exchange cartridge, analytes were converted to thiochromes with
      cyanogen bromide. For HPLC, a C-8 pre-column and a C-8 column connected to a
      NH(2) column were used with a fluorescence detector. No thiamin phosphates were
      found in egg yolk plasma or granules in native and embryonated eggs. The TH
      content in DM was 3,400 +/- 700 ng/g for yolk plasma, 1,500 +/- 140 ng/g for yolk
      granules of unincubated eggs, and 4,400 +/- 1,100 ng/g for yolk plasma and 2,100
      +/- 450 ng/g for yolk granules of 5-d embryonated eggs. In chick embryos, TH as
      well as thiamin phosphates were found. The mean content in 5-d-old embryos was
      1,200 +/- 400 ng of TH and 8,000 +/- 1,000 ng of TDP/g of DM. In 7-d-old embryos,
      the content of TH was 900 +/- 200 ng, TMP was 400 +/- 200 ng, and TDP was 5,500
      +/- 1,300 ng/g of DM. Thiamin triphosphate was not detected, and the minimum
      detectable limit for T was 0.3 ng/mL, for TMP 0.5 ng/mL, and for TDP 0.9 ng/mL,
      respectively. Recovery was 71% for TMP and 64% TDP in plasma and 58% TMP and 47%
      TDP in granules. It was demonstrated that only TH is present in egg yolk
      fractions in native and embryonated eggs of hens and that thiamin phosphates can
      be found in 5- and 7-d-old embryos, which indicates that they are synthesized by
      the chick embryo. According to its assumed unique role in highly specialized
      tissues, TTP was not found in early embryos.

PMID- 18079460
TI  - Analysis of plasma serotonin levels and hemodynamic responses following chronic
      serotonin infusion in broilers challenged with bacterial lipopolysaccharide and
      microparticles.
AB  - There has been extensive interest in the role of serotonin (5-hydoxytryptamine, 5
      HT) in the pathogenesis of pulmonary hypertension because episodes of pulmonary
      arterial hypertension in humans have been linked to serotoninergic appetite
      suppressant drugs. In this study, we investigated the role of serotonin in the
      development of pulmonary hypertension induced by intravenously injecting
      bacterial lipopolysaccharide (LPS, endotoxin) and cellulose microparticles. In
      experiment 1, we used a 5-HT ELISA kit for the in vitro quantitative
      determination of 5-HT in plasma during the development of pulmonary hypertension
      induced by injecting LPS and cellulose microparticles i.v. in broilers. In
      experiment 2, broilers were either chronically infused with 5-HT via surgically
      implanted osmotic pumps or received sham surgery as a control. After a period of
      10 d, the pulmonary arterial pressure was recorded during challenge with injected
      LPS or microparticles. Microparticles elicited 5-HT plasma levels more than 2
      fold greater than those elicited by LPS from 15 to 45 min postinjection. This
      indicates that 5-HT is an important mediator in the pulmonary hypertensive
      response of broilers to microparticles, but may not play a prominent role in the
      pulmonary hypertensive response to LPS. Furthermore, chronic 5-HT infusion via
      osmotic pumps caused an increase in the duration of the pulmonary hypertensive
      response of broilers to microparticles, indicating that the infused 5-HT was
      sequestered by circulating thrombocytes and then released upon microparticle
      mediated thrombocyte activation. Serotonin appears to play a less prominent role
      in the pulmonary hypertensive response of broilers to LPS, indicating that other
      mediators within the innate response to inflammatory stimuli may also be
      involved. These results are consistent with our hypothesis that pulmonary
      arterial hypertension ensues when vasoconstrictors such as 5-HT overwhelm the
      dilatory affects of vasodilators such as nitric oxide, thereby effectively
      reducing the pulmonary vascular capacity of pulmonary arterial hypertension
      susceptible broilers.

PMID- 18079461
TI  - Transpulmonary pressure gradient verifies pulmonary hypertension is initiated by
      increased arterial resistance in broilers.
AB  - Previous hemodynamic evaluations demonstrated that pulmonary arterial pressure
      (PAP) is higher in broilers that are susceptible to pulmonary hypertension
      syndrome (PHS, ascites) than in broilers that are resistant to PHS. We compared
      key pulmonary hemodynamic parameters in broilers from PHS-susceptible and PHS
      resistant lines (selected for 12 generations under hypobaric hypoxia) and in
      broilers from a relaxed (control) line. In experiment 1 the PAP was measured in
      male broilers in which a flow probe positioned on one pulmonary artery permitted
      the determination of cardiac output and pulmonary vascular resistance (PVR). The
      PAP and relative PVR were higher in susceptible broilers than in relaxed and
      resistant broilers, whereas absolute and relative cardiac output did not differ
      between lines. In experiment 2 male and female broilers from the 3 lines were
      catheterized to measure pressures in the wing vein, right atrium, right
      ventricle, pulmonary artery, and pulmonary veins (WP, wedge pressure). The
      transpulmonary pressure gradient (TPG) was calculated as (PAP-WP), with PAP
      quantifying precapillary pressure and WP approximating postcapillary pulmonary
      venous pressure. When compared with resistant and relaxed broilers, PAP values in
      susceptible broilers were > or =10 mmHg higher, TPG values were > or =8 mmHg
      higher, and WP values were < or =2 mmHg higher, regardless of sex. The combined
      hemodynamic criteria (elevated PAP and PVR combined with a proportionally
      elevated TPG) demonstrate that susceptibility to PHS can be attributed primarily
      to pulmonary arterial hypertension associated with increased precapillary
      (arteriole) resistance rather than to pulmonary venous hypertension caused by
      elevated postcapillary (venous and left atrial) resistance.

PMID- 18079462
TI  - The effect of ventilation on performance body and surface temperature of young
      turkeys.
AB  - Efficient ventilation affects thermoregulation and, thereby, the performance of
      domestic fowl. This became crucial as genetic selection for growth development
      significantly coupled with increased metabolic rate. The specific aims of this
      study were to elucidate a) the effects of different rates of ventilation on young
      turkey performance during exposure to constant 35, 30, and 25 degrees C and b)
      their effects on body temperature and surface temperature. In 3 separate
      experiments, turkeys were raised under regular conditions up to 3 wk of age.
      Thereafter, they were acclimated for 1 wk to the targeted ambient temperatures
      (T(a)) and to air velocities of 0.8, 1.5, 2.0, or 2.5 m/s and raised under those
      conditions up to 6 wk of age. Turkeys exposed to 35 degrees C performed optimally
      at an air velocity (AV) of 2 m/s; they exhibited significantly higher feed intake
      and significantly lower body temperature. At 30 degrees C, performance was
      optimal at AV of 1.5 to 2.5 m/s and significantly lower at 0.8 m/s. Performance
      of turkeys exposed to 25 degrees C did not vary with AV. Comparison of BW and
      feed intakes of turkeys exposed to the 3T(a) levels revealed significantly higher
      feed intake at 25 degrees C but similar BW compared with those exposed to 30
      degrees C, meaning that those exposed to 25 degrees C used more energy for
      maintenance than for growth. In general, surface temperature of the body declined
      significantly with T(a), whereas that of the face and legs was significantly
      lower at 25 degrees C. It can be concluded that AV affects the performance of
      young turkeys. The range of AV within which BW was optimal expanded as T(a)
      declined. It can be further concluded that the combination of 30 degrees C with
      AV from 1.5 to 2.5 m/s was optimal for young turkeys.

PMID- 18079463
TI  - Pulmonary hemodynamic responses to intravenous prostaglandin E2 in broiler
      chickens.
AB  - Prostaglandin E(2) (PGE(2)) affects pulmonary arterial pressure (PAP), pulmonary
      vascular resistance (PVR), and respiratory rate (RR) in mammals, but no
      information previously was available regarding avian pulmonary responses to
      PGE(2). Two experiments were conducted in which 45- to 55-d-old male broiler
      chickens were infused i.v. with PGE(2) at the lowest rate (30 mug/min for 4 min)
      that reliably reduced PAP during pilot studies. When compared with preinfusion
      (control) values in experiment 1, PGE(2) reduced PAP from 19 +/- 1 to 16 +/- 1
      mmHg (P < 0.001) and reduced mean systemic arterial pressure from 111 +/- 6 to 81
      +/- 5 mmHg (P < 0.001) but did not significantly reduce heart rate (HR; control:
      338 +/- 9 beats/min; PGE(2): 320 +/- 12 beats/min; P > 0.05). Infusing PGE(2)
      also reduced the RR from 57 +/- 2 to 46 +/- 4 breaths/min (P < 0.001) and reduced
      the percentage saturation of hemoglobin with oxygen (%HbO(2)) from 85 +/- 2 to 77
      +/- 3%HbO(2) (P < 0.001). After the PGE(2) infusion ceased, the PAP, mean
      systemic arterial pressure, RR, and %HbO(2) recovered within 8 min to levels that
      did not differ from preinfusion control values. In experiment 2, an ultrasonic
      flow probe was surgically implanted on 1 pulmonary artery to measure cardiac
      output (CO). When compared with preinfusion control values, PGE(2) reduced CO
      from 140 +/- 6 to 111 +/- 5 mL/kg of BW x min (P < 0.001), reduced PAP from 25 +/
      2 to 21 +/- 1 mmHg (P < 0.001), and reduced RR from 49 +/- 4 to 35 +/- 4
      breaths/min (P < 0.001). The reduction in CO was caused by a reduction in HR from
      305 +/- 9 to 260 +/- 9 beats/min without a significant reduction in stroke volume
      (control: 0.46 +/- 0.02 mL/kg of BW x beat; PGE(2): 0.43 +/- 0.02 mL/kg of BW x
      beat; P = 0.158). After the PGE(2) infusion ceased the CO, PAP, RR, and HR
      recovered within 9 min to levels that did not differ from preinfusion control
      values. The PVR, calculated as PAP/CO, was not altered by PGE(2) (control: 0.18
      +/- 0.01 relative resistance units; PGE(2): 0.20 +/- 0.02 relative resistance
      units; P > 0.723). These results indicate that in broilers PGE(2) reduced PAP by
      reducing CO rather than by acting as a pulmonary vasodilator to lower PVR. The
      PGE(2)-induced reductions in PAP would benefit broilers that are susceptible to
      pulmonary hypertension syndrome by reducing their right ventricular overload;
      however, the reductions in CO and RR combined with the onset of systemic arterial
      hypoxemia would accelerate the pathophysiological progression leading to terminal
      pulmonary hypertension syndrome.

PMID- 18079464
TI  - Inhaling one hundred percent oxygen eliminates the systemic arterial hypoxemic
      response of broilers to intravenous microparticle injections.
AB  - The pathogenesis of pulmonary hypertension syndrome (PHS, ascites) includes the
      development of systemic arterial hypoxemia (reduction in the saturation of
      hemoglobin with O(2), HbO(2)), which can be mimicked in clinically healthy
      broilers by i.v. injections of microparticles (MP). In experiment 1, arterial
      blood samples were collected from clinically healthy broilers before and after
      i.v. MP injections, and during a subsequent 100% O(2) inhalation period. The
      arterial samples were analyzed for HbO(2), partial pressure of O(2) and CO(2),
      and pH using a blood gas analyzer. In experiment 2, broilers that initially
      averaged > or =75% HbO(2) were assigned to a "high O(2)" group, whereas those
      that initially averaged < 75% HbO(2) were assigned to a "low O(2)" group. The
      HbO(2) and heart rate (HR) were measured using a pulse oximeter before, during,
      and after broilers in both groups inhaled 100% O(2). In experiment 3, HbO(2) and
      HR were measured using a pulse oximeter before, during, and after broilers
      inhaled 100% O(2), after i.v. MP injections, and during a second period of 100%
      O(2) inhalation. The HbO(2) rapidly decreased after i.v. MP injections, and
      subsequently providing 100% O(2) to breathe increased the HbO(2) above
      preinjection control levels in experiments 1 and 3. In experiment 2, inhaling
      100% oxygen eliminated the initial spontaneous differences in HbO(2) between the
      high O(2) and low O(2) groups, whereas the return to breathing ambient air
      restored the initial group differences in HbO(2). These experiments indicate that
      MP-induced and spontaneous hypoxemia can be attributed to a diffusion limitation
      rather than to arterial-venous shunts, because the hypoxemia resulting from
      arterial-venous shunts cannot be wholly eliminated by providing 100% O(2) to
      inhale.

PMID- 18079465
TI  - Semen quality factor as an indicator of fertilizing ability for geese.
AB  - The semen quality factor (SQF) takes into account 3 semen parameters as a means
      of predicting semen fertilizing ability: semen volume, semen concentration, and
      the percentage of live and morphologically normal spermatozoa. The objective of
      this study was to test the suitability of the SQF as an indicator of fertility
      for geese. Twenty-one ganders were divided into 3 groups based on their
      individual SQF values, and semen was pooled within each group. A fourth semen
      group was generated by diluting semen from the highest SQF group with 2 vol of
      diluent. Pooled semen was inseminated into 30 geese per treatment. Relationships
      between SQF and fertility were evaluated. Testosterone and estradiol levels in
      seminal plasma were determined by competitive immunoassays. The SQF values of the
      4 diluted semen groups were 19.3, 11.3, 9.5, and 13.1, and the corresponding
      fertility values, determined by candling, were 83.9, 65.6, 56.8, and 74.3%,
      respectively. The correlation coefficient between SQF and fertility was 0.985 (P
      < 0.01), indicating that the SQF can be used as a good indicator of fertility for
      geese. The SQF values correlated well with the ratio of testosterone to estradiol
      in seminal plasma (r = 0.48, P < 0.05), which could also be a diagnostic tool for
      evaluating the reproductive potential of individual ganders.

PMID- 18079466
TI  - Differences in carcass and meat characteristics between chicken indigenous to
      northern Thailand (Black-boned and Thai native) and imported extensive breeds
      (Bresse and Rhode Island red).
AB  - This study examined the effects of 4 genotypes of chicken, all suitable for
      extensive fattening, on carcass and meat quality using 320 chickens divided into
      4 equally sized groups. The comparison included 2 indigenous chicken strains from
      Thailand, Black-boned and Thai native (Thai), and 2 imported chicken breeds,
      Bresse and Rhode Island Red (Rhode, a layer breed). The animals were fed until 16
      wk of age. Breast (pectoralis major) and thigh (biceps femoris) muscles were
      studied in detail. Chickens of the imported breeds were heavier at slaughter than
      indigenous strains, especially Black-boned chickens. Proportions of retail cuts
      with bones were similar among genotypes, whereas deboned breast meat and
      lean:bone ratio were lowest in the layer breed (Rhode). The meat of the Black
      boned chickens was darker than that of the other genotypes. Thai and Rhode
      chickens had a particularly yellow skin. The ratio of red and intermediate to
      white fibers was higher in the thigh muscle, and the diameter of all muscle fiber
      types in both muscles was smaller in the indigenous compared with the imported
      breeds. The meat of the 2 indigenous Thai strains had lower contents of fat and
      cholesterol compared with that of the imported breeds, especially relative to the
      Rhode chickens (thigh meat). The meat of the indigenous origins, especially of
      the Thai chickens, was higher in shear force and collagen content (thigh only)
      than meat of the imported breeds. The meat lipids of the Thai chickens had
      particularly high proportions of n-3 fatty acids and a favorably low n-6/n-3
      fatty acid ratio compared with the other genotypes. In conclusion, meat of
      indigenous chickens has some unique features and seems to have more advantages
      over imported breeds than disadvantages, especially when determined for a niche
      market serving consumers who prefer chewy, low-fat chicken meat.

PMID- 18079467
TI  - Effect of commercial rosemary oleoresin preparations on ground chicken thigh meat
      quality packaged in a high-oxygen atmosphere.
AB  - Four commercial rosemary oleoresin preparations were added to ground chicken
      thigh meat at the recommended levels of the manufacturer then packaged in 80%
      O(2)-20% CO(2) modified atmosphere trays. The rosemary preparations differed in
      oil and water solubility, dispersion properties, or both. Addition of rosemary to
      ground chicken had an overall positive effect on raw meat appearance during
      storage and cooked meat flavor. No effect on bacterial growth was observed due to
      rosemary addition. However, oxidation was slowed in meat with added rosemary as
      indicated by lower TBA values, lower hexanal concentrations, and sensory scores.
      Color (redness) was more stable in meat with added rosemary compared with meat
      without rosemary, as reflected in redness (a*) values, hue angles, and visual
      scores. Of the 4 rosemary preparations tested, the oil-soluble, most concentrated
      preparation (HT-O) was most effective in maintaining meat quality compared with
      the other 3 types tested.

PMID- 18079468
TI  - Biochemical and physicochemical changes in spent hen breast meat during
      postmortem aging.
AB  - An experiment was conducted to study the biochemical and physicochemical changes
      with respect to improvement in tenderness of spent hen breast meat. Breast muscle
      obtained from freshly slaughtered spent hens (72 wk old) was divided into 5 equal
      lots and dipped in 1 mM NaN(3) before being packed in low-density poly-ethylene
      pouches under aerobic conditions and stored at refrigeration temperature (4
      degrees C). Lots were removed on 0, 7, 14, 21, and 28 d of storage and analyzed
      for pH, TBA reactive substances (TBARS), total sulfhydryl content, protein-bound
      sulfhydryl content, nonprotein-bound sulfhydryl content, perimysial fraction,
      collagen content, free OH-proline, N, nonprotein N, and proteolysis rate. Shear
      force value and penetrometer readings were also determined after making patties
      from the stored muscle samples. Results showed that pH values were gradually
      decreasing over the storage period. The TBARS values were increasing (P < 0.001),
      whereas the sulfhydryl content was decreasing (P < 0.001) over the storage
      period. The TBARS values were negatively (P < 0.05) correlated with total
      sulfhydryl content. This suggests that sulfhydryl content may prevent further
      higher oxidation of lipids. The soluble collagen content, collagen solubility,
      free OH-proline, and proteolysis rate were increasing (P < 0.001) during
      postmortem aging. These results suggest that collagen degradation into free amino
      acids occurs postmortem. A gradual decrease (P < 0.001) in shear force value and
      a gradual increase (P < 0.001) in penetrometer readings were recorded in the
      patties made from matured breast meat. Therefore, postmortem aging of spent hen
      breast meat resulted in 23% improvement in tenderness of minced patties on 14 d
      and 39% on 28 d as evidenced by biochemical and physicochemical changes.

PMID- 18079469
TI  - Occurrence, identification, and characterization of Campylobacter species
      isolated from portuguese poultry samples collected from retail establishments.
AB  - Campylobacter spp. are a leading cause of human diarrhea. The common source of
      infection is contaminated food, particularly poultry. From May 2005 to October
      2006, 164 samples of poultry obtained from several retail establishments and from
      different Portuguese producers were analyzed for the presence of Campylobacter
      spp. A total of 99 Campylobacter strains were isolated and further identified.
      Susceptibilities for 44 strains were determined for 11 antimicrobial drugs by the
      agar diffusion technique. According to the minimal inhibitory concentration for
      90% of the isolates, resistance to tetracycline, nalidixic acid, rifampicin,
      erythromycin, vancomycin and penicillin was observed. Sensitivity to gentamycin
      and chloramphenicol was also demonstrated. According to the antibiotic resistance
      profiles, the isolates appeared to differ from each other, including those that
      had been collected at the same period of time and from the same chicken sample.

PMID- 18079470
TI  - Influence of storage conditions and shotshell wounding on the hygienic condition
      of hunted, uneviscerated pheasant (Phasianus colchicus).
AB  - The effects of shot wounds on the hygienic conditions of pheasants (particularly
      those in the body cavity) were studied. Slaughtered (n = 33) and hunted pheasants
      (31 specimens with, and 33 specimens without shots in the body cavity) were
      stored uneviscerated at 0 and 4 degrees C. Specimens were taken at d 0, 3, 7, and
      14. Hunted pheasants differed from slaughtered pheasants with respect to muscular
      hemorrhages and blood and fecal matter in the body cavity but also with regard to
      the presence of Escherichia coli in breast and thigh muscles. In addition, a
      higher thigh muscle pH (P < 0.05) was noted in hunted pheasants, with no
      significant (P > 0.05) increase observed during storage. Concentrations of
      biogenic amines in muscle tissue remained below the determination limit of 1
      mg/kg for 90% of samples analyzed, with the maximum concentration for the
      remaining 10% of samples reaching 5.7 mg/kg, indicating a low incidence of
      contaminant bacteria. The observed changes in pH values and levels of biogenic
      amines failed to correlate with the presence or absence of shot lesions in the
      body cavity or abdominal region. Total aerobic counts increased significantly
      during storage, but the absolute numbers were consistently below 10(6) log(10)
      cfu/g. Although E. coli were <1 log(10) cfu/g in muscles of hunted pheasants on d
      3 at 4 degrees C, counts of up to 3.7 log(10) cfu/g on d 7 at 4 degrees C
      indicated a loss of hygienic quality. Therefore, it is recommended that hunted,
      uneviscerated pheasants be stored 3 d at 4 degrees C, but not longer than 7 d
      after the hunt.

PMID- 18079471
TI  - Forty-eight-hour cycle sequential feeding with diets varying in protein and
      energy contents: adaptation in broilers at different ages.
AB  - Sequential feeding is a cyclic feeding program with 2 diets for 1 or several days
      used to induce lower feed costs or to improve welfare quality. The aim of the
      present study was to investigate the effects of energy [2,800 (E-) and 3,200
      kcal/kg (E+)] and protein [230 (P+) and 150 g/kg (P-)] content on daily feed
      intake and growth in 900 male broiler chickens, and to compare these results with
      standard feeding (CP = 190 g/kg and ME = 3,000 kcal/kg). Sequential feeding was
      carried out during 48-h cycles in 2 periods (period 1 = 10 to 17 d of age, period
      2 = 18 to 29 d of age). Four treatments were compared during periods 1 and 2: 1)
      complete diet (C), 2) alternation of diets varying in CP (SP = P+ followed by P
      ), 3) in energy (S(E) = E- followed by E+), 4) in protein and energy contents
      (S(EPA) = P+E- followed by P-E+). A fifth treatment (S(EPB)) used an alternation
      in protein and energy contents during period 2 only. All chickens received the
      same feed during the finishing period (30 to 35 d of age). Feed intake was
      similar with sequential feeding and complete feed, but in proportion to total
      feed intake, chickens overconsumed high energy feeds (E+ and E+P-) during each
      period, and P- only for period 2 (P < 0.01). During period 2, overconsumption was
      greater with S(EPA) than S(EPB) (P < 0.01). Weight gain was similar for all
      treatments during period 1. At 35 d of age, S(E) chickens were heavier than
      S(EPA) and S(EPB) (P < 0.01). Feed to gain ratio was similar for all treatments
      for period 1 and increased for S(P), S(EPA), and S(EPB) compared with C and S(E)
      for period 2 (P < 0.01). Walking ability, carcass conformation, breast yield, and
      abdominal fat did not differ between treatments, but ultimate pH of breast meat
      was improved with S(P). In conclusion, growth and slaughtering performances
      similar to standard feeding can be reached with 48-h cycle sequential feeding
      using diets varying in protein and energy contents.

PMID- 18079472
TI  - Expression of the beta-catenin gene in the skin of embryonic geese during feather
      bud development.
AB  - beta-Catenin signaling has been reported to initiate feather bud development. In
      the present study, beta-catenin gene was isolated and identified from a cDNA
      library constructed using embryonic goose skin. Expression patterns of beta
      catenin gene in the dorsal skin of goose embryos were investigated using the
      methods of semi-quantitative reverse transcription PCR, Northern blot analysis,
      and in situ hybridization. The sequence of beta-catenin was found highly
      conserved at the amino acid level, sharing 100, 99, and 99% identity with
      chicken, Chinese soft-shell turtle, and human sequences, respectively. Relatively
      high levels (62.51 +/- 7.11% to 101.74 +/- 7.29%) of beta-catenin mRNA were
      detected in the dorsal skin samples. The levels of beta-catenin expression were
      most prominent at the early stage from embryo day (E)10 to E20 and then
      significantly declined with the embryonic development. In situ hybridization
      demonstrated that at E10, beta-catenin expression was mainly observed at the
      surface periderm cells and the localized region of the epidermal layer. Because
      feather bud forms with an anterior-posterior orientation, strong staining was
      observed in the periderm layer and in the ectoderm and epidermis with a diffuse
      distribution within the internal area of the buds. The stronger staining was seen
      in the barb ridges than in the center pulp of the feather follicles at E18 and
      E20. In this study, expression of Shh as a marker gene for the bud development
      was examined paralleling with expression patterns of beta-catenin. It was found
      that the expression pattern of beta-catenin was almost similar spatially and
      temporally to that of Shh mRNA at the later stages of bud development. The
      differential beta-catenin mRNA expression in the goose dorsal skin may be
      essential for promoting the normal development of embryonic feather bud.

PMID- 18079473
TI  - Formation mechanisms of melanoidins and fluorescent pyridinium compounds as
      advanced glycation end products.
AB  - The formation mechanisms of melanoidins as advanced glycation end products (AGEs)
      have not been resolved. Blue and red pigments generated in the D-xylose-glycine
      reaction system are postulated to be intermediate oligomers in the generation of
      melanoidins. A novel blue pigment, designated blue-M5, was identified as a
      similar structure to blue-M1 except for the side chain of two dihydroxypropyl
      groups. Blue pigments were also generated in the D-glucose-glycine and D-xylose
      beta-alanine reaction systems as well as in the D-xylose-glycine reaction system.
      Blue pigments by the Maillard reaction might be formed by the decarboxylation of
      two molecules of pyrrolopyrrole-2-carbaldehydes (PPA). PPA, composed of a side
      chain of a dihydroxypropyl group, was identified as a precursor of blue pigments.
      In fact, blue-M5 was generated by the incubation of PPA alone. Blue pigments,
      which involved pyrrolopyrrole structures, were readily changed to brown polymers.
      Glyceraldehyde-derived pyridinium (GLAP) compound, a glyceraldehyde-derived
      fluorescent AGE, and lysyl-pyrropyridine, a 3-deoxyglucosone-derived fluorescent
      AGE, were detected at higher levels in the plasma proteins and the tail tendon
      collagen of streptozotocin-induced diabetic rats compared to normal rats. GLAP
      and lysyl-pyrropyridine, therefore, might be related to the progression of
      diabetic complications.

PMID- 18079474
TI  - Methylglyoxal and methylglyoxal-arginine adducts do not directly inhibit
      endothelial nitric oxide synthase.
AB  - Increased formation of the reactive dicarbonyl compound methylglyoxal (MGO) and
      MGO-derived advanced glycation end products (AGEs) seems to be implicated in
      endothelial dysfunction and the development of diabetic vascular complications.
      MGO reacts with arginine residues in proteins to generate the major glycated
      adducts 5-hydro-5-methylimidazolone (MG-H1) and argpyrimidine (AP). We
      investigated whether the free forms of these adducts contribute to vascular cell
      dysfunction by inhibition of endothelial nitric oxide synthase (eNOS). MG-H1 and
      AP were synthesized and purified by reversed-phase chromatography, and the
      conversion of labeled L-arginine to L-citrulline was used to monitor eNOS
      activity. In contrast to the endogenous eNOS inhibitor asymmetric
      dimethylarginine (half maximal inhibitory concentration, approximately 5
      micromol/L), pathophysiological concentrations of MGO and MG-H1 and AP did not
      inhibit eNOS activity. Although MGO-derived AGEs are implicated in the
      development of diabetic vascular complications, this study indicates that this is
      not mediated via direct inhibition of eNOS activity.

PMID- 18079475
TI  - Immunological detection of N omega-(Carboxymethyl)arginine by a specific
      antibody.
AB  - N omega-(carboxymethyl)arginine (CMA) is an acid-labile advanced glycation end
      product (AGE) that was discovered in enzymatic hydrolysate of glycated collagen.
      Subsequently, CMA was also detected in human serum, and its level in patients
      with diabetes was found to be higher than in people without the disease. However,
      the histological localization of CMA and its pathophysiological significance
      remains poorly understood. Here, to address this issue, we developed a monoclonal
      antibody specific for CMA. This antibody reacted with CMA and CMA-protein adduct,
      whereas it did not cross-react with its analogues, such as N epsilon
      (carboxymethyl)lysine and S-(carboxymethyl)cysteine, indicating that the antibody
      specifically recognizes CMA. Upon immunohistochemical analysis, a significant CMA
      immnoreactivity was found in atherosclerotic lesions, whereas no such
      immunoreactivity was observed in normal regions. This suggests that the
      accumulation of CMA in tissue proteins may contribute to the pathophysiologies
      associated with aging and age-related diseases.

PMID- 18079476
TI  - Kinetic study of the reaction of glycolaldehyde with two glycation target models.
AB  - We have studied the reactivity of glycolaldehyde (GLA) with N-acetyl-Cys and N
      acetyl-Phe-Lys at physiological conditions of pH and temperature. The reaction
      between the N-Ac-Phe-Lys and GLA was studied in the presence of NaCNBH3 and then
      by using high-performance liquid chromatography (HPLC)-UV/Vis. The reaction
      between N-Ac-Cys and GLA was followed by stopped-flow spectroscopy with UV/Vis
      detection. Both the reduced Schiff base and thiohemiacetal were identified by 1H
      NMR and HPLC-mass spectrometry detection. The kinetic rate constant for the
      thiohemiacetal formation is four orders of magnitude higher than that for the
      Schiff base formation. This result suggests that the thiol group represents the
      most important target in protein glycation.

PMID- 18079477
TI  - Comparison of pharmacokinetics between highly and mildly modified AGE proteins in
      mice.
AB  - We previously demonstrated that RAW 264.7 cells (murine macrophage cell line)
      recognize highly modified advanced glycation end products (AGE)-bovine serum
      albumin (BSA) (high-AGE-BSA), which was prepared by incubating BSA with 1600
      mmol/L glucose for 40 weeks. In the present study, we prepared mildly modified
      AGE-BSA (mild-AGE-BSA) and conducted an endocytic uptake study using human
      monocyte-derived macrophages and Chinese hamster ovary cells which overexpressed
      such scavenger receptors as CD36, SR-BI (scavenger receptor class B type-I), and
      LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1). Although high
      AGE-BSA was significantly recognized by these cells, mild-AGE-BSA did not show
      any ligand activity to these cells. Furthermore, when 111 In-labeled mild- or
      high-AGE-BSA was injected into the tail vein of male ddY mice, 111 In-high-AGE
      BSA was rapidly cleared from the circulation, with about 80% of the injected 111
      In-high-AGE-BSA being eliminated within 5 min. In contrast, the clearance rate of
      111 In-mild-AGE-BSA was very slow, similar to the 111 In-native BSA. Taken
      together, our results indicate that the ligand activity of AGE-BSA to scavenger
      receptors and those pharmacokinetic properties depend on their rate of
      modification by AGEs.

PMID- 18079478
TI  - A419C (E111A) polymorphism of the glyoxalase I gene and vascular complications in
      chronic hemodialysis patients.
AB  - Advanced glycation end products (AGEs) take part in the pathogenesis of vascular,
      diabetic, and uremic complications. Their precursors are detoxified by the
      glyoxalase system. Our aim was to study A419C (E111A) single nucleotide
      polymorphism (SNP) of the glyoxalase I gene in hemodialysis (HD) patients. A419C
      SNP, several laboratory parameters including soluble receptor for AGEs (sRAGE),
      and clinical data were studied in 214 HD patients and 89 controls. Allelic and
      genotypic frequencies did not differ between HD patients and controls. A419C SNP
      was significantly linked with serum sRAGE, which sensitively reflects the AGE
      burden of the organism (3986 +/- 1638 pg/mL in the CC variant versus 3277 +/-
      1398 pg/mL in the AC variant and 3297 +/- 1445 pg/mL in the AA variant, P <
      0.01). In the CC variant, significantly higher prevalence of cardiovascular
      disease and peripheral vascular disease was found, while the prevalence of
      hypertension, diabetes mellitus, and dyslipidemia did not differ between
      genotypes. In summary, in this study we demonstrate for the first time the
      association of A419C polymorphism of the glyoxalase I gene with sRAGE levels and
      show the genetic predisposition to vascular complications in HD patients.

PMID- 18079479
TI  - Maillard reaction versus other nonenzymatic modifications in neurodegenerative
      processes.
AB  - Nonenzymatic protein modifications are generated from direct oxidation of amino
      acid side chains and from reaction of the nucleophilic side chains of specific
      amino acids with reactive carbonyl species. These reactions give rise to specific
      markers that have been analyzed in different neurodegenerative diseases sharing
      protein aggregation, such as Alzheimer's disease, Pick's disease, Parkinson's
      disease, dementia with Lewy bodies, Creutzfeldt-Jakob disease, and amyotrophic
      lateral sclerosis. Collectively, available data demonstrate that oxidative stress
      homeostasis, mitochondrial function, and energy metabolism are key factors in
      determining the disease-specific pattern of protein molecular damage. In
      addition, these findings suggest the lack of a "gold marker of oxidative stress,"
      and, consequently, they strengthen the need for a molecular dissection of the
      nonenzymatic reactions underlying neurodegenerative processes.

PMID- 18079480
TI  - The sense of smell: reception of flavors.
AB  - The sensory and hedonic evaluation of most food-related flavors is mainly
      dependent on olfactory perception. The sense of smell is able to recognize and
      discriminate myriads of airborne molecules with great accuracy and sensitivity.
      The primary processes of odor perception are mediated by the chemosensory
      olfactory neurons in the nasal epithelium, which upon interaction with
      appropriate odorants elicit a chemo-electrical transduction process converting
      the chemical signal into electrical impulses. The encoded information is conveyed
      onto distinct glomeruli, inducing topographic activity patterns in the olfactory
      bulb. The emerging chemotopic maps are decoded in the olfactory cortex, leading
      to the perception of distinct flavors.

PMID- 18079481
TI  - Nonenzymatically glycated lipoprotein ApoA-I in plasma of diabetic and
      nephropathic patients.
AB  - ApoA-I, which constitutes 70% of the apolipoprotein content of high-density
      lipoproteins, acts as an acceptor for the transfer of phospholipids and free
      cholesterol from peripheral tissues and transports cholesterol in the liver and
      other tissue for excretion and steroidogenesis. In order to verify its possible
      structural alteration in pathological states, plasma samples from healthy,
      diabetic, and nephropathic subjects have been analyzed by two-dimensional gel
      electrophoresis. By this approach, clear differences among the three classes of
      subjects become evident and, in the case of diabetic and nephropathic patients,
      intense spots are present. The matrix-assisted laser desorption/ionization mass
      spectrometry analysis of their digestion products shows that an overexpression of
      unglycated and glycated ApoA-I is present in both pathological states, reasonably
      affecting the efficiency in cholesterol transport.

PMID- 18079482
TI  - The aroma side of the Maillard reaction.
AB  - The Maillard reaction in food produces, among others, a diversity of sensory
      active compounds (aroma, taste, color). The resulting key aroma compounds are
      often present only in trace concentrations of 1 microg/kg to 1 mg/kg.
      Nevertheless, they contribute to the respective flavor because of their low odor
      perception thresholds. While Maillard intermediates, such as Amadori compounds
      and deoxyosones, are formed at percentage levels during model reactions, the
      yield of aroma compounds, in particular nitrogen and sulfur-containing ones, is
      often as low as 0.001-0.01 mol%, thus indicating their formation through chemical
      side reactions. The elucidation of the relevant precursors in food and the
      identification of previously unknown intermediates can throw light on these minor
      pathways. Also, model reactions with isotopically labeled precursors are of great
      value in gaining insight into the relevant formation mechanisms. Several examples
      of these studies are illustrated including work to elucidate the role of the
      solvent glycerol in the formation of pyrazines, trials to reveal the relative
      significance of 4-hydroxy-5-methyl-3(2H)-furanone as intermediate in the reaction
      between ribose and cysteine, and experiments to assess the proportional
      contribution of the precursors cysteine, xylose, and thiamine to the formation of
      the resulting aroma compounds in the thermal reaction.

PMID- 18079483
TI  - Suppression of renal alpha-dicarbonyl compounds generated following ureteral
      obstruction by kidney-specific alpha-dicarbonyl/L-xylulose reductase.
AB  - Renal unilateral ureteral obstruction (UUO) causes acute generation of alpha
      dicarbonyl stress substances, such as glyoxal, 3-deoxyglucosone, and
      methylglyoxal, in the kidneys. These alpha-dicarbonyl compounds are prone to form
      advanced glycation end products (AGEs) via the nonenzymatic Maillard reaction.
      Using transgenic (Tg) mice overexpressing a kidney-specific short-chain
      oxidoreductase, alpha-dicarbonyl/L-xylulose reductase (DCXR), we measured
      generation of alpha-dicarbonyls following UUO by means of electrospray
      ionization/liquid chromatography/mass spectrometry in their kidney extracts. The
      accumulation of 3-deoxyglucosone was significantly reduced in the kidneys of the
      mice Tg for DCXR compared to their wild-type littermates, demonstrating 4.91 +/-
      2.04 vs. 6.45 +/- 1.85 ng/mg protein (P = 0.044) for the obstructed kidneys, and
      3.68 +/- 1.95 vs. 5.20 +/- 1.39 ng/mg protein (P = 0.026) for the contralateral
      kidneys. Despite the reduction in accumulated alpha-dicarbonyls, collagen III
      content in kidneys of the Tg mice and their wild-type littermates showed no
      difference as monitored by in situ hybridization. Collectively, DCXR may function
      in the removal of renal alpha-dicarbonyl compounds under oxidative circumstances,
      but it is not sufficient to suppress acute renal fibrosis during 7 days UUO.

PMID- 18079484
TI  - N epsilon-(carboxymethyl)lysine during the early development of hypertension.
AB  - Advanced glycation end products (AGEs) are associated with hypertension. Whether
      N(epsilon)-(carboxymethyl)lysine (CML) contributes to the development of
      hypertension in young spontaneously hypertensive rats (SHR) remains to be
      established compared to WKY. We determined blood pressure, renal function, marker
      for oxidative stress (OS), and CML in young WKY rats and SHR. We found blood
      pressure was increased in SHR with no difference in renal function and OS
      compared to WKY. CML was elevated in plasma (2.3 +/- 0.3 vs. 1.3 +/- 0.2
      micromol/L) and kidney (1.0 +/- 0.1 vs. 0.5 +/- 0.1 micromol/L) compared to WKY.
      Early CML accumulation may contribute to the development of hypertension
      potentially by inducing early renal inflammation independent of glomerular
      dysfunction or oxidative stress.

PMID- 18079485
TI  - Receptor for advanced glycation end product polymorphisms and type 2 diabetes:
      the CODAM study.
AB  - Genetic variation in the receptor for advanced glycation end products (RAGE) gene
      may alter the expression and function of RAGE and affect disease development and
      outcome. We investigated whether single nucleotide polymorphisms (SNPs) in RAGE
      were associated with diabetes and parameters of glucose homeostasis. In total,
      nine SNPs of RAGE were analyzed in individuals with and without type 2 diabetes
      in CODAM: a cohort study of diabetes and atherosclerosis, Maastricht. A
      significant difference in genotype frequency of SNP rs3134945 was observed
      between the nondiabetic control subjects, subjects with impaired glucose
      metabolism, and diabetic patients. The C allele of this polymorphism was
      significantly associated with higher fasting glucose concentrations, 2-h postload
      glucose concentrations, insulin levels, and homeostasis model assessment of
      insulin resistance. These results indicate that SNP rs3134945 or a locus in
      linkage disequilibrium with this polymorphism may be involved in the development
      of insulin resistance and diabetes. Because the functionality of this
      polymorphism is not known, the mechanism whereby this polymorphism contributes to
      the development of insulin resistance and diabetes has to be further elucidated.

PMID- 18079486
TI  - Some natural compounds enhance N epsilon-(carboxymethyl)lysine formation.
AB  - Since pyridoxamine, which traps intermediates in the Maillard reaction and lipid
      peroxidation reaction, significantly inhibits the development of retinopathy and
      neuropathy in the streptozotocin-induced diabetic rat, treatment with advanced
      glycation end product inhibitors and antioxidants may be a potential strategy for
      the prevention of clinical diabetic complications. However, the paradoxical
      effect of green tea has been reported; although plasma hydroperoxide levels were
      ameliorated, the level of N epsilon-(carboxyethyl)lysine (CML) in tendon and
      plasma was increased by the oral administration of green tea to diabetic rats. In
      the present study, we measured the effect of natural compounds on CML formation
      by enzyme-linked immunosorbent assay. A significant amount of CML was observed
      when bovine serum albumin was incubated with ribose for 7 days. Under the same
      conditions, natural compounds, such as desgalactotigonin, showed inhibitory
      effects, whereas quercetin and acteoside enhanced CML formation, indicating that
      natural compounds contain both inhibitors and enhancers for CML formation.

PMID- 18079487
TI  - Maillard reaction products in the Escherichia coli-derived therapeutic protein
      interferon alfacon-1.
AB  - We have recently shown that recombinant human interferon-gamma is affected by
      early stages of the Maillard reaction during its production in Escherichia coli.
      Over time, advanced glycation end products accumulated in the purified protein,
      accompanied with degradation, cross-linking, and a drop in the protein's biologic
      activity. Here, we provide further evidence for the presence of Maillard reaction
      products in another E. coli-derived therapeutic protein, interferon alfacon-1.
      These products might interfere with both treatment efficacy and patient safety.

PMID- 18079488
TI  - Usefulness of antibodies for evaluating the biological significance of AGEs.
AB  - Polyclonal and monoclonal antibodies have been widely applied to demonstrate the
      presence of advanced glycation end products (AGEs) in vivo. However, our previous
      study showed that monoclonal anti-AGE antibody (6D12) and polyclonal anti-N
      epsilon-(carboxymethyl)lysine (CML) antibody recognize not only CML but also N
      epsilon-(carboxyethyl)lysine (CEL), thus indicating that we should pay attention
      to the specificity of the antibodies. As a result, we prepared specific
      monoclonal antibodies against CML, CEL, N omega-(carboxymethyl)arginine (CMA),
      and S-(carboxymethyl)cysteine (CMC). Our immunochemical study using anti-CMA
      antibody demonstrated that the CMA content increased in a time-dependent manner
      when collagen was incubated with glucose, indicating that immunological
      quantification using the specific antibody is especially useful for measuring an
      acid-labile AGE structure, such as CMA. Monoclonal antibody is also applied to
      identify a novel biological marker in pathological lesions. We prepared antibody
      libraries against proteins modified with aldehydes, such as glyoxal,
      methylglyoxal, and glycolaldehyde (GA), and one antibody, GA5, which specifically
      reacts with the GA-modified protein that is recognized in human atherosclerotic
      lesions. Following successive high-performance liquid chromatography
      purification, the GA5-reactive compound was isolated and its chemical structure
      was found to be 3-hydroxy-4-hydroxymethyl-1-(5-amino-5-carboxypentyl) pyridinium
      cation, which was named GA-pyridine. Taken together, these results demonstrate
      that a specific antibody is a powerful tool for analyzing novel biomarkers,
      formation pathways, and the efficacy of AGE inhibitors.

PMID- 18079489
TI  - Cigarette smoke induces an unfolded protein response in the human lung: a
      proteomic approach.
AB  - Cigarette smoking, which exposes the lung to high concentrations of reactive
      oxidant species (ROS) is the major risk factor for chronic obstructive pulmonary
      disease (COPD). Recent studies indicate that ROS interfere with protein folding
      in the endoplasmic reticulum and elicit a compensatory response termed the
      "unfolded protein response" (UPR). The importance of the UPR lies in its ability
      to alter expression of a variety of genes involved in antioxidant defense,
      inflammation, energy metabolism, protein synthesis, apoptosis, and cell cycle
      regulation. The present study used comparative proteomic technology to test the
      hypothesis that chronic cigarette smoking induces a UPR in the human lung.
      Studies were performed on lung tissue samples obtained from three groups of human
      subjects: nonsmokers, chronic cigarette smokers, and ex-smokers. Proteomes of
      lung samples from chronic cigarette smokers demonstrated 26 differentially
      expressed proteins (20 were up-regulated, 5 were down-regulated, and 1 was
      detected only in the smoking group) compared with nonsmokers. Several UPR
      proteins were up-regulated in smokers compared with nonsmokers and ex-smokers,
      including the chaperones, glucose-regulated protein 78 (GRP78) and calreticulin;
      a foldase, protein disulfide isomerase (PDI); and enzymes involved in antioxidant
      defense. In cultured human airway epithelial cells, GRP78 and the UPR-regulated
      basic leucine zipper, transcription factors, ATF4 and Nrf2, which enhance
      expression of important anti-oxidant genes, increased rapidly (< 24 h) with
      cigarette smoke extract. These data indicate that cigarette smoke induces a UPR
      response in the human lung that is rapid in onset, concentration dependent, and
      at least partially reversible with smoking cessation. We speculate that
      activation of a UPR by cigarette smoke may protect the lung from oxidant injury
      and the development of COPD.

PMID- 18079490
TI  - Combustion-derived hydrocarbons localize to lipid droplets in respiratory cells.
AB  - Combustion-generated radicals interact to form polynuclear aromatic hydrocarbons
      (PAHs), including carcinogens. PAHs aggregate into 20- to 50-nm particles, which
      extend into branched-chain structures (soots). Incomplete combustion yields black
      soot particles and black smoke. Many PAHs, including those in soots, fluoresce
      upon excitation. We have reported that butadiene soot (BDS), generated during
      combustion of the high-volume petrochemical 1,3-butadiene, serves as a
      reproducible example of combustion-derived fine and ultrafine particles, with the
      potential for acute or delayed health effects. Human bronchoepithelial cells
      (BEAS-2B) display time- and concentration-dependent responses to BDS exposure,
      culminating in concentration of fluorescent PAHs within discrete cytoplasmic
      bodies. Here we identify the cytoplasmic compartment(s) in which combustion
      derived PAHs concentrate and assess the metabolic responses associated with this
      compartmentalization. BDS-associated fluorescence colocalized with a red
      fluorescent cholesterol analog and a transfected plasmid coding for a fluorescent
      lipid droplet surface protein within BEAS-2B cells. After BDS exposure, murine
      alveolar macrophages (MH-S) and adipocytes (3T3-L1) also develop fluorescence.
      These findings, especially within adipocytes, support the accumulation of PAHs
      within lipid droplets. Microarray data revealed up-regulation of aryl hydrocarbon
      receptor-induced Phase I biotransformation enzymes and nuclear erythroid-2
      related factor 2-mediated oxidative stress responses in BEAS-2B cells.
      Quantitative RT-PCR results confirmed a time-dependent up-regulation of Phase I
      biotransformation enzymes (CYP1A1, CYP1B1, and ALDH3A1) in BDS-exposed BEAS-2B
      and MH-S cells. Thus, respiratory cell lipid droplets concentrate PAHs delivered
      by combustion-derived ultrafine particles. These PAHs, including several found in
      BDS and in cigarette smoke, activate xenobiotic metabolism pathways and thereby
      potentiate their toxicity.

PMID- 18079491
TI  - Beta-tryptase regulates IL-8 expression in airway smooth muscle cells by a PAR-2
      independent mechanism.
AB  - Mast cells are central in the development of several allergic diseases and
      contain a number of pre-formed mediators. beta-tryptase, the most abundant mast
      cell product, is increasingly recognized as a key inflammatory mediator, as it
      causes the release of cytokines, particularly the chemokine IL-8, from both
      inflammatory and structural cells. The molecular mechanisms, however, remain
      largely unknown. In this study we sought to investigate whether beta-tryptase
      could induce IL-8 expression in human airway smooth muscle (ASM) cells and to
      explore the molecular mechanisms involved. We found that purified human beta
      tryptase stimulated IL-8 production in a time- and concentration-dependent
      manner, which was inhibited by protease inhibitors and mimicked by recombinant
      human beta-tryptase, but not by the protease-activated receptor-2 (PAR-2) agonist
      SLIGKV-NH(2), consistent with the low-level expression of PAR-2 protein in these
      cells. beta-tryptase also up-regulated IL-8 mRNA expression, as analyzed by RT
      PCR and real-time PCR, which was abolished by the transcription inhibitor
      actinomycin D. Reporter gene assay showed that beta-tryptase-induced IL-8
      transcription was mediated by the transcription factors activator protein-1,
      CCAAT/enhancer binding protein, and NF-kappaB, and chromatin immunoprecipitation
      assay demonstrated that beta-tryptase induced in vivo binding of these
      transcription factors to the IL-8 gene promoter. Furthermore, beta-tryptase
      stabilized IL-8 mRNA, suggesting additional post-transcriptional regulation.
      Collectively these findings show that beta-tryptase up-regulates IL-8 expression
      in ASM cells through a PAR-2-independent proteolytic mechanism and coordinated
      transcriptional and post-transcriptional regulation, which may be of particular
      importance in understanding the role and the mechanisms of action of beta
      tryptase in regulating chemokine expression in mast cell-related disorders.

PMID- 18079492
TI  - MUC1 mucin is a negative regulator of toll-like receptor signaling.
AB  - MUC1 (MUC1 in humans and Muc1 in nonhuman species) is a transmembrane mucin-like
      glycoprotein expressed in epithelial cells lining various mucosal surfaces as
      well as hematopoietic cells. Recently, we showed that Muc1(-/-) mice exhibited
      greater inflammatory responses to Pseudomonas aeruginosa or its flagellin
      compared with their wild-type littermates, and our studies with cultured cells
      revealed that MUC1/Muc1 suppressed the Toll-like receptor (TLR) 5 signaling
      pathway, suggesting its anti-inflammatory role. Here we demonstrate that other
      TLR signaling (TLR2, 3, 4, 7, and 9) is also suppressed by MUC1/Muc1. The results
      from this study suggest that MUC1/Muc1 may play a crucial role during airway
      infection and inflammation by various pathogenic bacteria and viruses.

PMID- 18079493
TI  - Inflammatory profile of new bacterial strain exacerbations of chronic obstructive
      pulmonary disease.
AB  - RATIONALE: Whether the airway and systemic inflammatory profile in bacterial
      exacerbations of chronic obstructive pulmonary disease (COPD) is distinct from
      nonbacterial exacerbations is unclear. Previous studies have not used molecular
      typing of bacterial pathogens, which is required to accurately define bacterial
      infection in COPD. The relationship between clinical severity and course of
      exacerbation and inflammation is also not fully understood. OBJECTIVES: To
      determine if (1) systemic and airway inflammation is distinct in new bacterial
      strain exacerbations and (2) clinical severity and resolution of exacerbations is
      related to airway and systemic inflammation. METHODS: In a prospective
      longitudinal cohort study in COPD, sputum and serum samples obtained before, at,
      and following exacerbations during a 2-year period were studied. MEASUREMENTS AND
      MAIN RESULTS: Clinical information, molecular typing of bacterial pathogens,
      sputum IL-8, tumor necrosis factor (TNF)-alpha and neutrophil elastase, and serum
      C-reactive protein. From 46 patients, 177 exacerbations were grouped as new
      strain, preexisting strain, other pathogen, and pathogen negative. New strain
      exacerbations were associated with significantly greater increases from baseline
      in sputum TNF-alpha and neutrophil elastase, and in serum C-reactive protein
      compared with the other three groups. Increases in inflammatory markers were
      similar among the other three groups. Clinical resolution was accompanied by
      resolution of inflammation to preexacerbation levels, whereas persistent symptoms
      were paralleled by persistently elevated inflammation. Clinical exacerbation
      severity was significantly correlated with levels of all four markers.
      CONCLUSIONS: Neutrophilic airway inflammation and systemic inflammation are more
      intense with well-defined bacterial exacerbations than with nonbacterial
      exacerbations. Clinical course of exacerbation and inflammation are closely
      linked.

PMID- 18079494
TI  - Development of chronic bronchitis and emphysema in beta-epithelial Na+ channel
      overexpressing mice.
AB  - RATIONALE: Chronic obstructive pulmonary disease is a leading cause of death
      worldwide, but its pathogenesis is not well understood. Previous studies have
      shown that airway surface dehydration in beta-epithelial Na(+) channel (betaENaC)
      overexpressing mice caused a chronic lung disease with high neonatal pulmonary
      mortality and chronic bronchitis in adult survivors. OBJECTIVES: The aim of this
      study was to identify the initiating lesions and investigate the natural
      progression of lung disease caused by airway surface dehydration. METHODS: Lung
      morphology, gene expression, bronchoalveolar lavage, and lung mechanics were
      studied at different ages in betaENaC-overexpressing mice. MEASUREMENTS AND MAIN
      RESULTS: Mucus obstruction in betaENaC-overexpressing mice originated in the
      trachea in the first days of life and was associated with hypoxia, airway
      epithelial necrosis, and death. In surviving betaENaC-overexpressing mice, mucus
      obstruction extended into the lungs and was accompanied by goblet cell
      metaplasia, increased mucin expression, and airway inflammation with transient
      perinatal increases in tumor necrosis factor-alpha and macrophages, IL-13 and
      eosinophils, and persistent increases in keratinocyte-derived cytokine (KC),
      neutrophils, and chitinases in the lung. betaENaC-overexpressing mice also
      developed emphysema with increased lung volumes, distal airspace enlargement, and
      increased lung compliance. CONCLUSIONS: Our studies demonstrate that airway
      surface dehydration is sufficient to initiate persistent neutrophilic airway
      inflammation with chronic airways mucus obstruction and to cause transient
      eosinophilic airway inflammation and emphysema. These results suggest that
      deficient airway surface hydration may play a critical role in the pathogenesis
      of chronic obstructive pulmonary diseases of different etiologies and serve as a
      target for novel therapies.

PMID- 18079495
TI  - PHOX2B germline and somatic mutations in late-onset central hypoventilation
      syndrome.
AB  - RATIONALE: Late-onset central hypoventilation syndrome (LO-CHS) is a rare
      disorder that may manifest as early as infancy or as late as during adulthood.
      The potential overlap of LO-CHS with congenital CHS is under debate, even though
      both disorders can result from heterozygous PHOX2B gene mutations. OBJECTIVES: To
      characterize the PHOX2B status in a series of 25 patients with LO-CHS referred
      from 3 months of age to adulthood. Whenever a PHOX2B mutation was identified, we
      ascertained its germline or somatic origin in both patients with LO-CHS and in 15
      parents of probands with congenital CHS found to harbor a PHOX2B mutation.
      METHODS: The PHOX2B gene was analyzed by direct DNA sequencing and origin of the
      mutation evaluated by fluorescent PCR. MEASUREMENTS AND MAIN RESULTS: We have
      identified a heterozygous PHOX2B gene mutation in 17 of 25 patients with LO-CHS.
      The far most frequent mutation results in a germline +5 alanine expansion in the
      series of 20 alanines (15 cases) that show incomplete penetrance and variable
      expressivity, possibly resulting from combined environmental and genetic factors.
      PHOX2B frameshift and missense mutations have also been identified in patients
      with LO-CHS. Importantly, one parent found to harbor a somatic mosaic for a +8
      alanine expansion developed alveolar hypoventilation in his 40s. CONCLUSIONS:
      These data indicate that PHOX2B gene mutations should be systematically examined
      in any adult with unexplained central hypoventilation and raise the question of
      follow-up for apparently healthy parents found to harbor a somatic mosaic for the
      PHOX2B mutation identified in their child.

PMID- 18079496
TI  - Negative-pressure ventilation: better oxygenation and less lung injury.
AB  - RATIONALE: Conventional positive-pressure ventilation delivers pressure to the
      airways; in contrast, negative pressure is delivered globally to the chest and
      abdomen. OBJECTIVES: To test the hypothesis that ventilation with negative
      pressure results in better oxygenation and less injury than with positive
      pressure. METHODS: Anesthetized, surfactant-depleted rabbits were ventilated for
      2.5 hours in pairs (positive or negative). Tidal volume was 12 ml . kg(-1),
      normocapnia was maintained by adjusting respiratory rate, and Fi(O(2)) was 1.0.
      MEASUREMENTS AND MAIN RESULTS: Lung injury was assessed with histologic scoring,
      perfusion using thermodilution (global perfusion), and injected intravascular
      microspheres (regional perfusion); and dynamic computed tomography was used to
      determine inflation patterns. Negative pressure was associated with a higher
      Pa(O(2)), a lower Pa-Pet(CO(2)) gradient (despite identical minute ventilation),
      and less lung injury. Lung perfusion (global and regional) was similar with
      positive and negative pressure. Positive end-expiratory pressure applied to the
      airway was more efficiently transmitted to the pleural space than comparable
      levels of negative end-expiratory pressure applied to the chest wall; however,
      the oxygenation associated with any level of end-expiratory lung volume was
      greater when achieved by negative versus positive pressure. Dynamic computed
      tomography suggested that lung distension achieved with negative pressure is
      characterized by greater proportions of normally aerated lung (with less
      atelectasis) during inspiration and at end-expiration. CONCLUSIONS: Negative
      pressure ventilation results in superior oxygenation that is unrelated to lung
      perfusion and may be explained by more effective inflation of lung volume during
      both inspiration and expiration.

PMID- 18079497
TI  - Serodiagnosis of Mycobacterium avium-complex pulmonary disease using an enzyme
      immunoassay kit.
AB  - RATIONALE: The diagnosis of Mycobacterium avium-complex pulmonary disease (MAC
      PD) and/or its discrimination from pulmonary tuberculosis (TB) is sometimes
      complicated and time consuming. OBJECTIVES: We investigated in a six-institution
      multicenter study whether a serologic test based on an enzyme immunoassay (EIA)
      kit was useful for diagnosing MAC-PD and for distinguishing it from other lung
      diseases. METHODS: An EIA kit detecting serum IgA antibody to glycopeptidolipid
      core antigen specific for MAC was developed. Antibody levels were measured in
      sera from 70 patients with MAC-PD, 18 with MAC contamination, 37 with pulmonary
      TB, 45 with other lung diseases, and 76 healthy subjects. MEASUREMENTS AND MAIN
      RESULTS: Significantly higher serum IgA antibody levels were detected in patients
      with MAC-PD than in the other groups (P < 0.0001). Setting the cutoff point at
      0.7 U/ml resulted in a sensitivity and specificity of the kit for diagnosing MAC
      PD of 84.3 and 100%, respectively. Significantly higher antibody levels were also
      found in patients with nodular-bronchiectatic disease compared with fibrocavitary
      disease in MAC-PD (P < 0.05). There was a positive correlation between the extent
      of disease on chest computed tomography scans and the levels of antibody (r =
      0.43, P < 0.05) in patients with MAC-PD. CONCLUSIONS: The EIA kit is useful for
      the rapid diagnosis of MAC-PD and for differentiating MAC-PD from pulmonary TB
      and, if validated by studies in other populations, could find wide application in
      clinical practice.

PMID- 18079498
TI  - IRF-1 gene variations influence IgE regulation and atopy.
AB  - RATIONALE: The development of atopic diseases is characterized by skewed immune
      responses to common allergens. Only recently, interferons have been identified to
      play a crucial role in these mechanisms. OBJECTIVES: Because interferon
      regulatory factor (IRF)-1 is critical for interferon expression, we tested the
      hypotheses that genetic changes in this essential transcription factor may have
      consequences for the development of atopy. METHODS: The IRF-1 gene locus was
      resequenced in 80 human chromosomes. Association and haplotype analyses were
      performed in a cross-sectional study population of German children from Dresden
      (n = 1,940), and results were replicated in a second population sample from
      Munich (n = 1,159), both part of the ISAAC (International Study of Asthma and
      Allergy in Childhood) phase II. Promoter polymorphism effects were studied using
      electrophoretic mobility shift assay and colorimetric binding assays. Allele
      specific IRF-1 gene expression was studied in vitro using luciferase reporter
      assays, whereas we assessed ex vivo expression of IRF-1 by real-time polymerase
      chain reaction and IFN-gamma protein by Luminex technology (Bio-Rad, Hercules,
      CA). Statistical analyses were performed using SAS/Genetics (SAS 9.1.3; SAS
      Institute, Cary, NC). MEASUREMENTS AND MAIN RESULTS: By resequencing, 49
      polymorphisms were identified within the IRF-1 gene. Four blocks containing 11
      polymorphisms were significantly associated with atopy, total IgE levels, or
      specific IgE levels in both populations (P < 0.05). Two polymorphisms changed
      transcription factor binding of nuclear factor (NF)-kappaB and EGR1 (early growth
      response 1) to the IRF-1 promoter, altered gene expression in vitro (P = 0.0004),
      and altered IRF-1 mRNA and IFN-gamma protein expression ex vivo. CONCLUSIONS: Our
      results suggest that functionally relevant IRF-1 polymorphisms influence atopy
      risk, potentially by altering transcription factor binding, IRF-1 gene
      expression, and IFN-gamma regulation.

PMID- 18079499
TI  - Commentary on psychiatric resident education in intellectual disabilities.

PMID- 18079500
TI  - Hide and seek: the elusive rural psychiatrist.

PMID- 18079501
TI  - Putting "rural" into psychiatry residency training programs.
AB  - OBJECTIVE: Evidence indicates disparities in the number of psychiatrists
      practicing in rural America compared to urban areas suggesting the need for a
      greater emphasis on rural psychiatry in residency training programs. The authors
      offer suggestions for integrating a rural focus in psychiatry residency training
      to foster greater competency and interest in rural psychiatry. METHODS: The
      authors surveyed the limited rural psychiatry training and the more extensive
      family medicine rural residency literature to review efforts to develop rural
      focused training curricula. RESULTS: Many factors in the rural environment
      influence mental health care, including overlapping professional-patient
      relationships, caregiver isolation and stress, limited availability and access to
      mental health resources, disease stigma, and economic and health status. To
      enhance both an interest in and the quality of the training for a rural practice,
      the authors suggest three levels of training for integrating rural factors into
      psychiatry programs from a basic didactic understanding of the contextual issues
      affecting rural psychiatry, to creating rural clinical experiences and
      preceptors, to developing a rural psychiatry fellowship. CONCLUSIONS: Providing
      trainees with an understanding of the rural mental health issues and experiences
      might contribute to trainees' selecting rural practices and enhance the rural
      competency of psychiatrists.

PMID- 18079502
TI  - Psychiatric resident education in intellectual disabilities: one program's ten
      years of experience.
AB  - OBJECTIVE: The authors evaluated the confidence and willingness of resident
      graduates to treat individuals with intellectual disability (ID), following a
      residency rotation in developmental disability. METHODS: Thirty-two graduates of
      a single residency program were surveyed regarding their post-residency
      experience with patients with intellectual disability. All graduates had
      completed a 3 month, half-time residency rotation in intellectual disability. The
      anonymous 12-question survey sought feedback about satisfaction with the
      rotation, confidence in serving persons with ID, and actual post-residency work
      with ID patients. RESULTS: Twenty-three of 32 (72%) of graduates returned
      surveys. On a 6-point scale (1=strongly disagree; 6=strongly agree), residents
      most strongly endorsed that the rotation had built their capacity in ID (5.78),
      confidence (5.48), and satisfaction (5.37). Lowest ratings were given to
      professional contact in ID initiated by the graduate (2.74), identifying
      expertise to the community (3.22), and post-residency practice with patients with
      ID (3.30). Differences between respondents who identified post-residency contact
      with persons with ID (N=8), and respondents who did not (N=15), did not reach
      statistical significance. CONCLUSIONS: Psychiatric graduates appear to value
      specialized education and experience in working with ID patients during
      residency, and feel more confident as a result. In spite of this, the majority of
      resident graduates did not identify ID training or expertise to their practice
      community, or choose to work with ID patients following residency.

PMID- 18079503
TI  - Resident education and perceptions of recovery in serious mental illness:
      observations and commentary.
AB  - OBJECTIVE: Recovery is emerging as a guiding influence in mental health service
      delivery and transformation. As a consequence, the expectations and curricular
      needs of trainees (as future stakeholders in a transformed, recovery-oriented
      system) are now of considerable importance. METHOD: To this end, resident-led
      focus groups were held at the Medical College of Georgia to obtain perceptions of
      the Recovery Model. Certified Peer Support Specialists (CPSS) attended and topics
      covered were the Recovery Model, the CPSS training curriculum, and developing a
      Wellness Recovery Action Plan (WRAP) with consumers. RESULTS: Advantages and
      disadvantages of the Recovery model were discussed, with residents generally
      expressing cautious optimism regarding implementation of these principles, yet
      concern regarding the potential for diminishing confidence and support for
      traditional professional services. All residents indicated an interest in
      obtaining more information about the Recovery Model, including how to incorporate
      WRAPS and the role of CPSS in Recovery. Almost half of the residents selected a
      recovery-oriented workshop as the best method for further education about these
      concepts, with less support for other options of didactic handouts and expert
      lecture. CONCLUSIONS: Future efforts should be directed at implementing recovery
      curricula into resident education and evaluating the changes in resident
      knowledge, attitude toward recovery, and plans to implement recovery-oriented
      principles into their own professional practice.

PMID- 18079504
TI  - Increasing the rate of return of resident rotation evaluations by their attending
      physicians in an in-patient psychiatric facility.
AB  - OBJECTIVE: Psychiatrist's evaluations of residents are the primary means of
      determining whether the residents are ready to be promoted. However, the return
      rate for evaluations is quite low. The purpose of this study was to increase the
      return rates. METHODS: Feedback from two surveys and open discussion was utilized
      to develop and implement a system for increasing completion rates. Completion
      rates before and after the intervention were compared. RESULTS: The survey
      revealed that the initial evaluation form was too complex and not readily
      available. In addition, participants indicated that reminders would be helpful
      for increasing compliance. Completion rates were 48% and 80% for the 4 months
      prior and after the intervention, respectively. CONCLUSION: Addressing the
      problem and implementing suggested strategies increased completion rates
      significantly. However, it is unclear which strategy was most associated with the
      change. Future directions will focus on determining whether gains will be
      maintained and what would be necessary to obtain 100% compliance rates.

PMID- 18079505
TI  - The Structured Clinically Relevant Interview for Psychiatrists in Training
      (SCRIPT): a new standardized assessment tool for recruitment in the uk.
AB  - OBJECTIVE: The multifaceted nature of training and the diverse backgrounds of
      potential Senior House Officers (Postgraduate Residents) require a novel approach
      to the selection of trainees wishing to pursue a career in psychiatry. The author
      reports the properties of a semi-structured interview (the SCRIPT) for assessing
      doctors short-listed for a large Senior House Officer Training Scheme in
      psychiatry in South East England. METHODS: Data from 3 recruitment periods
      between 2005 and 2006 was examined to assess both interrater reliability and
      variation in scoring between interviewers. All questions were operationally
      defined and were modeled on General Medical Council (UK) guidelines for Good
      Medical Practice. RESULT: For 3 consecutive recruitment periods, interrater
      reliability (measured by Cronbach alpha) retained a high level of significance
      (p<0.001). Differences between the maximum and minimum mean scores between panels
      differed by only 6% of the total possible score and differences between mean
      scores at the same (p values between 0.8 and 0.9) and different (p values between
      0.2 and 0.4) interviews showed no significant differences. CONCLUSIONS: The
      development of a valid and reliable method for selecting Senior House Officers in
      Psychiatry shows promise in the recruitment of "tomorrow's psychiatrists."
      Prospective data on the positive predictive value of individual scores in career
      development awaits further exploration. Given the birth of a new 'Run Through
      Grade,' the interview may have its place in the assessment process within
      Modernising Medical Careers in the United Kingdom.

PMID- 18079506
TI  - Assessing attitudes about genetic testing as a component of continuing medical
      education.
AB  - OBJECTIVE: To investigate the attitudes among mental health professionals
      regarding the use of genetic testing. METHODS: Psychiatrists and other mental
      health professionals (N=41) who were enrolled in a week-long course in
      psychiatric genomics completed questionnaires before and after the course
      designed to assess how diagnostic genetic tests should be used and the value of
      pharmacogenomic testing for clinical practice. RESULTS: Only 5% of the course
      participants knew their genotype for the CYP 2D6 and CYP 2C19 genes at the time
      they participated in the course. However, after completing the course, 95% of the
      participants who had not been tested responded that they would be tested if
      genotyping was provided at no cost. Most of the participants reported that adults
      have the right to know their genotypes. Specifically, a majority of participants
      also reported that adults should have access to information regarding their
      genetic predispositions to both Huntington's disease and Alzheimer's disease. A
      majority of participants believed that parents had the right to know the
      genotypes of their children and that adolescents should have access to their
      genotypes if they had parental permission or were emancipated minors. However,
      only 29% of participants reported that children ages 6 to 12 should have access
      to the results of their genotyping. CONCLUSION: Continuing medical educational
      programs can provide an effective and informative opportunity to develop a better
      understanding of contemporary perspectives of practicing clinicians. Despite some
      variability in beliefs regarding the implications of age and diagnosis for making
      genetic testing decisions, a majority of course participants reported that they
      would choose to be genotyped for two drug metabolizing enzyme genes. Furthermore,
      they felt that, in most circumstances, adults should be permitted to know their
      genotype.

PMID- 18079507
TI  - Developing the master educator: cross disciplinary teaching scholars program for
      human and veterinary medical faculty.
AB  - OBJECTIVE: At the University of California, Davis (UCD), the authors sought to
      develop an institutional network of reflective educational leaders. The authors
      wanted to enhance faculty understanding of medical education's complexity, and
      improve educators' effectiveness as regional/national leaders. METHODS: The UCD
      Teaching Scholars Program is a half-year course, comprised of 24 weekly half-day
      small group sessions, for faculty in the School of Medicine and Veterinary
      Medicine. The program's philosophical framework was centered on personal
      reflection to enhance change: 1) understanding educational theory to build
      metacognitive bridges, 2) diversity of perspectives to broaden horizons, 3)
      colleagues as peer teachers to improve interactive experiences, and 4) reciprocal
      process of testing theory and examining practice to reinforce learning. The
      authors describe the program development (environmental analysis, marketing,
      teaching techniques), specific challenges, and failed experiments. The authors
      provide examples of interactive exercises used to enhance curricular content. The
      authors enrolled 7-10 faculty per year, from a diverse pool of current and near
      future educational leaders. RESULTS: Four years of Teaching Scholars participants
      were surveyed about program experiences and short/longer term outcomes. Twenty
      six (76%) respondents reported that they were very satisfied with the course
      (4.6/5), individual curricular blocks (4.2-4.6), and other faculty (4.7). They
      described participation barriers/facilitators. Participants reported positive
      impact on their effectiveness as educators (100%), course directors (84%),
      leaders (72%), and educational researchers (52%). They described specific
      acquired attitudes, knowledge, and skills. They described changes in their
      approach to education/career changed based on program participation. Combining
      faculty from different educational backgrounds significantly broadened
      perspectives, leading to greater/new collaboration. DISCUSSION: Developing a
      cadre of master educators requires careful program planning, implementation, and
      program/participant evaluation. Based on participant feedback, our program was a
      success at stimulating change. This open assessment of programmatic strengths and
      weaknesses may provide a template for other medical institutions that seek to
      enhance their institutional educational mission.

PMID- 18079508
TI  - Fifteen years of evolution as a society of teaching scholars.

PMID- 18079509
TI  - Teaching scholars programs: faculty development for educators in the health
      professions.
AB  - OBJECTIVE: This article 1) provides an overview of formal Health Sciences
      Teaching Scholars Programs as presented in medical education literature and 2)
      presents information about an innovative multidiscipline Teaching Scholars
      Program. METHOD: Health Sciences Teaching Scholars Programs and similar programs
      were reviewed in the medical education literature to identify similar and
      dissimilar characteristics. The WVU Teaching Scholars Program highlighted in this
      article is presented with a discussion of goals, objectives, target audiences,
      course length, session frequency, program topics, learning methods, and
      assessments of the programs. A summary of the WVU Teaching Scholars Program and
      two Teaching Scholars Programs at McGill University and the University of Toronto
      were presented at the Association for American Medical Colleges (AAMC) annual
      meeting in 2006 for input from the general medical education audience. RESULTS:
      Comparisons of Health Sciences Teaching Scholars Programs reveal that successful
      programs are uniquely shaped by their educational environments. Scholars report
      that they value learning new teaching methods and improving their educational
      careers. CONCLUSION: Teaching Scholars Programs are valuable for the development
      of enhancing both teaching and scholarship in Health Sciences Programs and must
      adapt to the uniqueness of their respective educational environments and must
      continue to nurture scholars beyond graduation.

PMID- 18079510
TI  - Neurobiological formulations: integrating clinical and biological psychiatry.
AB  - OBJECTIVE: The authors describe a pilot program allowing psychiatric residents to
      participate in neurobiological evaluations of patients with Axis I disorders. The
      program aimed to familiarize residents with available tools for assessing
      cognitive and neuroanatomical abnormalities in psychiatric patients and to foster
      greater interest among residents in correlating psychiatric symptoms with
      abnormalities in neural structures and pathways. METHODS: Residents meet weekly
      with a faculty mentor to plan and construct a neurobiological formulation.
      Residents review the salient literature on the Axis I condition present in a
      patient of their choosing. The patient undergoes neuroanatomical, physiological,
      and cognitive testing relevant to his disorder. The resident then integrates the
      findings from this testing with the patient's clinical presentation. Using a
      questionnaire, the authors obtain feedback from residents based on residents'
      experiences with this didactic program. RESULTS: Residents felt they obtained a
      greater appreciation and understanding of the relevance of neuroanatomical and
      neurophysiological abnormalities and testing in clinical psychiatry. The project
      was well received and residents rated it highly for its educational value.
      CONCLUSION: Neurobiological formulations offer a new educational method to foster
      knowledge and interest among psychiatric residents about the importance of
      neuroscience in clinical practice.

PMID- 18079511
TI  - The fall and redemption of people and systems: potential lessons from the "star
      wars" saga.
AB  - Through an analysis of the fall and redemption of Anakin Skywalker and the
      Galactic Republic of the Star Wars saga, educators may be able to convey valuable
      lessons to students learning about child and adolescent psychiatry and to junior
      psychiatrists learning about psychiatric administration and liaison.
      Specifically, educators may be able to convey that 1) when caring for patients
      who have succumbed or are at risk of succumbing to "darkness" in the modern
      psychiatric sense (e.g., violence and criminal behavior), it is important to
      recognize risk factors as well as protective factors that can lead to successful
      "salvation"; and 2) when administering or serving as a liaison to systems of
      care, it is important to acknowledge and heal dysfunctions in the relevant
      "system."

PMID- 18079512
TI  - A future for geriatric psychiatry?

PMID- 18079514
TI  - Optimal design of an internal monitoring program for personnel in the Chornobyl
      exclusion zone radwaste management industrial complex.
AB  - Modern state and approach regarding organisation of individual internal dose
      monitoring of the personnel of industrial complex for radioactive waste
      management at the Chornobyl exclusion zone (CEZ) is presented. Sensitivity and
      adequacy of the acknowledged instrumental methods is considered taking into
      account the features of interpretation using indirect methods in the specific
      working conditions of industrial complex for radioactive waste management at the
      CEZ. The performed analysis enables clear recommendations to be made with regard
      to optimum design of an internal monitoring program for personnel, including
      application of specific techniques.

PMID- 18079516
TI  - Regulation of drugs for children in Europe.

PMID- 18079515
TI  - Review of standards of protection for pregnant workers and their offspring.
AB  - The recommendations of the International Commission on Radiological Protection
      and the IAEA Basic Safety Standards (BSS) make clear that the embryo and fetus
      should be regarded as a member of the public when considering the protection of
      female workers who are or may be pregnant. The BSS note that the embryo and fetus
      should be 'afforded the same broad level of protection as required for members of
      the public'. Similar guidance is included in national legislation in a number of
      countries. On the basis of a review of such guidance, it was concluded that
      although the recommendations provided in the BSS are in general agreement with
      the international consensus on approaches to the protection of pregnant workers
      and their offspring, more specific supporting guidance is needed. The IAEA is
      preparing a technical document that extends and clarifies previous advice and
      considers the practical application of the advice for workers in different types
      of workplace, for which important potential routes of exposure for the pregnant
      worker have been identified. This action is being carried out under the framework
      of the International Action Plan for Occupational Radiation Protection.

PMID- 18079517
TI  - The future for trainee doctors.

PMID- 18079518
TI  - Assuring the confidentiality of shared electronic health records.

PMID- 18079519
TI  - Prognostic pessimism: Not all bad?

PMID- 18079520
TI  - Prognostic pessimism: Don't group COPD and asthma.

PMID- 18079521
TI  - Prostate cancer screening: Unacceptable in the under 50s.

PMID- 18079522
TI  - Doctors and the state: How much longer will patients trust us?

PMID- 18079523
TI  - Use of patients' data: GMC guidance on confidentiality.

PMID- 18079524
TI  - Caesarean section: Points raised in responses.

PMID- 18079525
TI  - Diarrhoeal diseases still kill more than 1.5m children under 5 each year.

PMID- 18079526
TI  - WHO launches campaign to make drugs safer for children.

PMID- 18079527
TI  - Drug companies expected to get more leeway in communicating with patients in
      Europe.

PMID- 18079529
TI  - Opposition grows in France to new charges for drugs and ambulance trips.

PMID- 18079531
TI  - FDA may allow drug and device companies to promote "off-label" uses.

PMID- 18079533
TI  - NHS trusts lambasted for failing to tackle race inequality.

PMID- 18079534
TI  - GMC approves change in the standard of proof.

PMID- 18079535
TI  - UK government to spend 105m pounds sterling to improve stroke services.

PMID- 18079538
TI  - Europe's research councils call for spending to be doubled to 0.25% of GDP.

PMID- 18079539
TI  - UK government sets up pilot studies to evaluate medical abortion services outside
      hospitals.

PMID- 18079540
TI  - Use military and private sector to cope with disasters, aid agencies told.

PMID- 18079542
TI  - Minority groups still show high rates of admission to mental health services in
      England and Wales.

PMID- 18079544
TI  - Thin living.

PMID- 18079545
TI  - Steps to a leaner Europe.

PMID- 18079546
TI  - Being an NHS manager is a fool's errand.

PMID- 18079547
TI  - A remedy for lonely hearts?

PMID- 18079548
TI  - Unequal weight: equity oriented policy responses to the global obesity epidemic.

PMID- 18079549
TI  - Cystic fibrosis.

PMID- 18079550
TI  - Investigating rectal bleeding.

PMID- 18079551
TI  - Management of atopic eczema in children aged up to 12 years: summary of NICE
      guidance.

PMID- 18079557
TI  - The area postrema: a brain monitor and integrator of systemic autonomic state.
AB  - The area postrema is a medullary structure lying at the base of the fourth
      ventricle. The area postrema's privileged location outside of the blood-brain
      barrier make this sensory circumventricular organ a vital player in the control
      of autonomic functions by the central nervous system. By virtue of its lack of
      tight junctions between endothelial cells in this densely vascularized structure
      and the presence of fenestrated capillaries, peptide and other physiological
      signals borne in the blood have direct access to neurons that project to brain
      areas with important roles in the autonomic control of many physiological
      systems, including the cardiovascular system and systems controlling feeding and
      metabolism. However, the area postrema is not simply a conduit through which
      signals flow into the brain, but it is now being recognized as the initial site
      of integration for these signals as they enter the circuitry of the central
      nervous system.

PMID- 18079558
TI  - Prophylactic training in asymptomatic soccer players with ultrasonographic
      abnormalities in Achilles and patellar tendons: the Danish Super League Study.
AB  - BACKGROUND: A recent study published in The American Journal of Sports Medicine
      showed that asymptomatic soccer players with an increased risk of developing
      Achilles and patellar tendon injuries within the next 12 months can be identified
      with use of ultrasonography. HYPOTHESIS: Prophylactic eccentric training and
      stretching can reduce both the frequency of asymptomatic ultrasonographic changes
      in Achilles and patellar tendons in soccer players and the risk of these
      asymptomatic intratendinous changes becoming symptomatic. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 1. METHODS: Two hundred and nine
      Danish professional soccer players from the best national league (Super League)
      were followed over 12 months with use of ultrasonography and injury registration.
      Half the teams were randomized to an intervention group with prophylactic
      eccentric training and stretching of the Achilles and patellar tendons during the
      soccer season. RESULTS: The eccentric training and stretching did not reduce the
      injury risk, and, contrary to all expectations, the injury risk during the season
      was increased in players with abnormal patellar tendons at the beginning of the
      study in January. Eccentric training and stretching in players with normal
      patellar tendons significantly reduced the proportion of players with
      ultrasonographic changes in the patellar tendons at the end of the season (risk
      difference [RD] = 12%; 95% confidence interval [CI], 2%-22%; P = .02), but the
      training had no effect on the Achilles tendons (RD = 1%; 95% CI, -7% to 9%; P =
      .75). The presence of preseason ultrasonographic abnormalities in the tendons
      significantly increased the risk of developing tendon symptoms during the season
      (relative risk = 1.9; 95% CI, 1.2-3.1; P = .009). CONCLUSIONS: This study
      demonstrates that with the use of ultrasonography, tendon changes in soccer
      players can be diagnosed before they become symptomatic. The prophylactic
      eccentric training and stretching program reduces the risk of developing
      ultrasonographic abnormalities in the patellar tendons but has no positive
      effects on the risk of injury. On the contrary, in asymptomatic players with
      ultrasonographically abnormal patellar tendons, prophylactic eccentric training
      and stretching increased the injury risk.

PMID- 18079559
TI  - Charge scan reveals an extended region at the intracellular end of the GABA
      receptor pore that can influence ion selectivity.
AB  - Selective permeability is a fundamental property of ion channels. The Cys-loop
      receptor superfamily is composed of both excitatory (ACh, 5-HT) and inhibitory
      (GABA, glycine) neurotransmitter-operated ion channels. In the GABA receptor, it
      has been previously shown that the charge selectivity of the integral pore can be
      altered by a single mutation near the intracellular end of the second
      transmembrane-spanning domain (TM2). We have extended these findings and now show
      that charge selectivity of the anionic rho1 GABA receptor can be influenced by
      the introduction of glutamates, one at a time, over an 8-amino acid stretch (-2'
      to 5') in the proposed intracellular end of TM2 and the TM1-TM2 intracellular
      linker. Depending on the position, glutamate substitutions in this region
      produced sodium to chloride permeability ratios (P(Na)+(/Cl)-) varying from 0.64
      to 3.4 (wild type P(Na)+(/Cl)- = 0). In addition to providing insight into the
      mechanism of ion selectivity, this functional evidence supports a model proposed
      for the homologous nicotinic acetylcholine receptor in which regions of the
      protein, in addition to TM2, form the ion pathway.

PMID- 18079560
TI  - KCNE peptides differently affect voltage sensor equilibrium and equilibration
      rates in KCNQ1 K+ channels.
AB  - KCNQ1 voltage-gated K(+) channels assemble with the family of KCNE type I
      transmembrane peptides to afford membrane-embedded complexes with diverse channel
      gating properties. KCNQ1/KCNE1 complexes generate the very slowly activating
      cardiac I(Ks) current, whereas assembly with KCNE3 produces a constitutively
      conducting complex involved in K(+) recycling in epithelia. To determine whether
      these two KCNE peptides influence voltage sensing in KCNQ1 channels, we monitored
      the position of the S4 voltage sensor in KCNQ1/KCNE complexes using cysteine
      accessibility experiments. A panel of KCNQ1 S4 cysteine mutants was expressed in
      Xenopus oocytes, treated with the membrane-impermeant cysteine-specific reagent 2
      (trimethylammonium) ethyl methanethiosulfonate (MTSET), and the voltage-dependent
      accessibility of each mutant was determined. Of these S4 cysteine mutants, three
      (R228C, G229C, I230C) were modified by MTSET only when KCNQ1 was depolarized. We
      then employed these state-dependent residues to determine how assembly with KCNE1
      and KCNE3 affects KCNQ1 voltage sensor equilibrium and equilibration rates. In
      the presence of KCNE1, MTSET modification rates for the majority of the cysteine
      mutants were approximately 10-fold slower, as was recently reported to indicate
      that the kinetics of the KCNQ1 voltage sensor are slowed by KCNE1 (Nakajo, K.,
      and Y. Kubo. 2007 J. Gen. Physiol. 130:269-281). Since MTS modification rates
      reflect an amalgam of reagent accessibility, chemical reactivity, and protein
      conformational changes, we varied the depolarization pulse duration to determine
      whether KCNE1 slows the equilibration rate of the voltage sensors. Using the
      state-dependent cysteine mutants, we determined that MTSET modification rates
      were essentially independent of depolarization pulse duration. These results
      demonstrate that upon depolarization the voltage sensors reach equilibrium
      quickly in the presence of KCNE1 and the slow gating of the channel complex is
      not due to slowly moving voltage sensors. In contrast, all cysteine substitutions
      in the S4 of KCNQ1/KCNE3 complexes were freely accessible to MTSET independent of
      voltage, which is consistent with KCNE3 shifting the voltage sensor equilibrium
      to favor the active state at hyperpolarizing potentials. In total, these results
      suggest that KCNE peptides differently modulate the voltage sensor in KCNQ1 K(+)
      channels.

PMID- 18079562
TI  - Hereditary haemochromatosis.

PMID- 18079561
TI  - Sulfonylurea receptors type 1 and 2A randomly assemble to form heteromeric KATP
      channels of mixed subunit composition.
AB  - ATP-sensitive potassium (K(ATP)) channels play important roles in regulating
      insulin secretion, controlling vascular tone, and protecting cells against
      metabolic stresses. K(ATP) channels are heterooctamers of four pore-forming
      inwardly rectifying (Kir6.2) subunits and four sulfonylurea receptor (SUR)
      subunits. K(ATP) channels containing SUR1 (e.g. pancreatic) and SUR2A (e.g.
      cardiac) display distinct metabolic sensitivities and pharmacological profiles.
      The reported expression of both SUR1 and SUR2 together with Kir6.2 in some cells
      raises the possibility that heteromeric channels containing both SUR subtypes
      might exist. To test whether SUR1 can coassemble with SUR2A to form functional
      K(ATP) channels, we made tandem constructs by fusing SUR to either a wild-type
      (WT) or a mutant N160D Kir6.2 subunit. The latter mutation greatly increases the
      sensitivity of K(ATP) channels to block by intracellular spermine. We expressed,
      individually and in combinations, tandem constructs SUR1-Kir6.2 (S1-WT), SUR1
      Kir6.2[N160D] (S1-ND), and SUR2A-Kir6.2[N160D] (S2-ND) in Xenopus oocytes, and
      studied the voltage dependence of spermine block in inside-out macropatches over
      a range of spermine concentrations and RNA mixing ratios. Each tandem construct
      expressed alone supported macroscopic K(+) currents with pharmacological
      properties indistinguishable from those of the respective native channel types.
      Spermine sensitivity was low for S1-WT but high for S1-ND and S2-ND. Coexpression
      of S1-WT and S1-ND generated current components with intermediate spermine
      sensitivities indicating the presence of channel populations containing both
      types of Kir subunits at all possible stoichiometries. The relative abundances of
      these populations, determined by global fitting over a range of conditions,
      followed binomial statistics, suggesting that WT and N160D Kir6.2 subunits
      coassemble indiscriminately. Coexpression of S1-WT with S2-ND also yielded
      current components with intermediate spermine sensitivities, suggesting that SUR1
      and SUR2A randomly coassemble into functional K(ATP) channels. Further
      pharmacological characterization confirmed coassembly of not only S1-WT and S2
      ND, but also of coexpressed free SUR1, SUR2A, and Kir6.2 into functional
      heteromeric channels.

PMID- 18079563
TI  - Probiotics and remission of ulcerative colitis: a systematic review.
AB  - BACKGROUND: Ulcerative colitis (UC) is an acute and inflammatory disease of the
      large bowel of unknown aetiology. The use of probiotics for this disease remains
      controversial. The objective of this systematic review was to identify studies
      based on randomised controlled trials comparing the effect of probiotics to the
      effect of anti-inflammatory drugs or placebo in the remission of UC. METHODS: We
      conducted a systematic review of clinical trials comparing the effect of
      probiotics to the effect of anti-inflammatory treatment or placebo in the
      remission of UC. PubMed, scienceDirect, Cochrane, Google scholar, metaRegister of
      Controlled Trials and National Institutes of Health were searched. RESULTS: Nine
      studies met the inclusion criteria. These studies present a significant
      heterogeneity concerning their methodology and their results. The improvement in
      UC remission and the frequency of adverse effects do not differ significantly
      between probiotic and control groups. CONCLUSIONS: There are a limited number of
      randomised trials published in the field of probiotics used for the remission of
      UC, and they present many methodological differences. The existing studies
      suggest a similar safety and efficacy of probiotics in comparison with anti
      inflammatory drugs.

PMID- 18079564
TI  - Changing aspects of HFE-related hereditary haemochromatosis and endeavours to
      early diagnosis.
AB  - HFE-related hereditary haemochromatosis (HH) is an iron overload disease
      attributed to the highly prevalent homozygosity for the C282Y mutation in the HFE
      gene. The pathophysiology of this error in iron metabolism is not completely
      elucidated yet, although deficiency of the iron regulatory hormone hepcidin
      appears to play a role. Ways of diagnosing iron overload include measurement of
      the serum iron parameters, i.e. serum transferrin saturation and serum ferritin,
      by a liver biopsy or by calculating the amount of mobilisable body iron withdrawn
      by phlebotomies. Clinical signs attributed to HFE-related HH include liver
      failure, arthralgia, chronic fatigue, diabetes mellitus and congestive heart
      failure. organ failure can be prevented by phlebotomies starting before
      irreversible damage has occurred. Therefore, screening to facilitate early
      diagnosis is desirable in individuals at risk of developing HFE-related iron
      overload. over time it appeared that the clinical penetrance of the HFE mutations
      was much lower than had previously been thought. This changed the opinion about a
      suitable screening modality from case detection, via population screening, to
      family screening as the most appropriate method to prevent HFE-related disease.
      However, before the implementation of family screening it is vital to have
      thorough information on the relevance of the specific health problem involved, on
      the clinical penetrance of C282Y homozygosity and on the effectiveness of the
      screening approach.

PMID- 18079565
TI  - Morbidity and mortality in first-degree relatives of C282Y homozygous probands
      with clinically detected haemochromatosis compared with the general population:
      the HEmochromatosis FAmily Study (HEFAS).
AB  - BACKGROUND: Family screening has been suggested as a sophisticated model for the
      early detection of HFE-related hereditary haemochromatosis (HH). However, until
      now, controlled studies on the morbidity and mortality in families with HH are
      lacking. METHODS: Data on iron parameters, morbidity and mortality were collected
      from 224 dutch C282Y-homozygous probands with clinically overt HH and 735 of
      their first-degree family members, all participating in the HEmochromatosis
      fAmily study (HEfAs). These data were compared with results obtained from an age-
      and gender-matched normal population. HEfAs and controls filled in similar
      questionnaires on demographics, lifestyle factors, health, morbidity and
      mortality. RESULTS: A significantly higher proportion of the HEfAs first-degree
      family members reported to be diagnosed with haemochromatosis-related diseases:
      45.7 vs 19.4% of the matched normal population (McNemar p<0.001). Mortality among
      siblings, children and parents in the HEFAS population was similar to that in the
      relatives of matched control. CONCLUSION: In this study we show that, morbidity
      among first-degree family members of C282Y-homozygous probands previously
      diagnosed with clinically proven HH is higher than that in an age- and gender
      matched normal population. Further studies are needed to definitely connect these
      increase morbidity figures to increase prevalenc of the C282Y mutated HFE-gene
      and elevated serum iron indices.

PMID- 18079566
TI  - Incidence of first acute myocardial infarction in the Netherlands.
AB  - OBJECTIVES: To study the incidence of first acute myocardial infarction (AMi) in
      the Netherlands. BACKGROUND: We recently showed that AMi patients can be followed
      longitudinally within dutch national medical registrations in a valid way. This
      makes it possible to provide nationwide incidence estimates of first AMi in the
      Netherlands. METHODS: New cases of first AMi in the dutch population in 2000 were
      identified through linkage of the national hospital discharge register, the
      population register and the cause of death statistics and included hospitalised
      first Ami patients and out-of-hospital deaths from first AMi. RESULTS: 31,777
      patients with a first AMi were identified. The incidence (per 100,000 persons per
      year) increased from 2 in men aged <30 years to 2996 in men aged > or = 90 years.
      Corresponding figures for women ranged from 1 to 2226. The incidence was higher
      in men than in women in all age groups, but the male-to-female ratio decreased
      after the age of 50-59 year. Of all first AMI patients, 40% died before being
      admitted to a hospital. The proportion of non-hospitalised AMI patients increased
      with age in men after the age of 50-59 years. Within the age groups the
      proportion of out-of-hospital deaths was similar for men and women. CONCLUSION:
      Our study provides the first nationwide incidence estimates of first AMI in the
      Netherlands. Expected differences in incidence with regard to age and gender were
      shown. The large proportion of out-of-hospital deaths reinforces the importance
      of primary prevention AMI.

PMID- 18079567
TI  - Failure of CHOP with rituximab for lymphomatoid granulomatosis.
AB  - We present a 66-year-old male patient with pulmonary lymphomatoid granulomatosis.
      The patient had progressive disease after three courses of CHoP and rituximab
      and, therefore, treatment with interferon-alpha 2b 5 x 10(6) IE three times a
      week was started. This resulted in stable disease for five months. subsequently,
      progression occurred and the patient died 12 months after initial presentation.
      lymphomatoid granulomatosis is a rare, poor-risk, Epstein-Barr virus related, B
      cell lymphoproliferative disease. There is no standard treatment but promising
      results have been reported with rituximab, either as monotherapy or in
      combination with chemotherapy. This case demonstrates that lymphomatoid
      granulomatosis is still a chemotherapy-resistant disease in some patients despite
      addition of rituximab. A review of the literature regarding aetiology, clinical
      features, diagnosis and treatment options is presented.

PMID- 18079568
TI  - Watery diarrhoea: an unusual manifestation of breast cancer.
AB  - Analysis of an 83-year-old male presenting with diarrhoea showed secretory
      diarrhoea. serum levels of gastrin and pancreatic polypeptide were elevated.
      Somatostatin-receptor scintigraphy revealed a hot spot in the left thoracic wall
      and subsequently, breast adenocarcinoma with neuroendocrine differentiation was
      diagnosed. Postoperatively, the patient made an uneventful recovery. The
      relationship between the clinical picture, the results of pathological
      examination and hormonal analysis is discussed and put into perspective.

PMID- 18079569
TI  - Synopsis of the Dutch multidisciplinary guideline for the diagnosis and treatment
      of hereditary haemochromatosis.
AB  - Hereditary haemochromatosis (HH) is a disease related to mutations in the HFE
      gene and can lead to progressive iron accumulation, especially in the liver,
      eventually resulting in organ damage. We have developed guidelines for the
      diagnosis and treatment of this disease according to CBO methodology (dutch
      institute for Healthcare Quality). The prevalence of clinical symptoms such as
      fatigue, arthropathies, impotence and diabetes mellitus among homozygotes was
      similar to that in a control population. Nevertheless, we recommend the
      assessment of serum iron indices when these symptoms remain unexplained. When
      transferrin saturation is >45% and ferritin exceeds local reference ranges, HFE
      mutations should be investigated. Homozygosity for the C282Y mutation or combined
      C282Y/H63d mutation confirms the diagnosis of HFE-related HH. Liver biopsy is
      recommended when ferritin exceeds 1000 microg/l to establish the presence or
      absence of cirrhosis, which will affect prognosis and management. iron
      accumulation confirmed by magnetic resonance imaging (MRI) in the absence of the
      homozygous C282Y mutation or the combined C282Y/H63d genotype may justify a
      search for rare hereditary forms of non-HFE HH in a specialised centre. The
      literature supports the benefits of adequate phlebotomy and the screening of
      first-degree relatives of index patients with clinically overt HH. overall, the
      guidelines presented here are to a great extent based on the expert opinion of
      the working party, as the quantity of evidence that met predefined criteria posed
      by the evidence-based approach was small. We therefore recommend world-wide
      efforts to collaboratively address these remaining issues.

PMID- 18079570
TI  - Spontaneous fistulisation of a liver abscess into the stomach.

PMID- 18079571
TI  - Patient with diarrhoea, abdominal pain and weight loss.

PMID- 18079572
TI  - Blurred vision.

PMID- 18079573
TI  - Denying open access to published health-care research: WHO has the password?

PMID- 18079574
TI  - Methods of intervention in reducing the psychosocial impact while dealing with
      cancer as a disease: a clinician's point of view.
AB  - AIMS AND OBJECTIVE: We searched for the clinically relevant suggestions,
      recommendations and findings amongst the papers on Psycho-oncology. The term
      clinically relevant for us meant 'practical and implemental modes of intervention
      that contribute but would not affect or interfere with the normal functioning of
      the present system and treatment modality of the patients.' Our intention was to
      use the available information for the benefit of our patients. We also searched
      for the data that would prove the significance of these methods. In most parts of
      the world it is not possible to involve a psychologist at every level of cancer
      care. Based on the findings, we intend to carry out our own project for the
      psychosocial intervention in cancer patients and make suggestions that could be
      adopted even by those who have little or no experience in psychology. CONCLUSION:
      The field of psycho oncology is a relatively new and evolving subspecialty of
      oncology and psychology at the same time. Current data and papers, which would
      make simple and implemental modes of intervention at psychosocial level, are
      limited. There is a dire necessity of solid data and list of suggestions to the
      specialists, non-specialists and to those who take care of the cancer patients,
      to enhance the care they provide to the cancer patients.

PMID- 18079575
TI  - On the transit dose from motorized wedge treatment in Equinox-80 telecobalt unit.
AB  - PURPOSE: To estimate the transit dose from motorized wedge (MW) treatment in
      Equinox-80 telecobalt machine. MATERIALS AND METHODS: Two plans were generated in
      Eclipse treatment planning system with universal wedge (UW) and MW each for 10 x
      10 cm 2 . The transit dose was measured with 0.6 cc cylindrical ion chamber and
      thermoluminescent dosimeters (TLD) chips at a depth of 5 cm with source to axis
      distance (SAD) 80 cm. RESULTS: The measured dose with ion chamber was in well
      agreement with the calculated dose from Eclipse within +/- 2%. The planned dose
      was 100 cGy while the measured absorbed dose with ion chamber for 15 degrees , 30
      degrees , 45 degrees and 60 degrees MW treatment was found to be 100.94, 101.04,
      100.72 and 99.33 cGy respectively. For 15 degrees , 30 degrees , 45 degrees and
      60 degrees UW treatment, the measured absorbed dose was 99.33, 97.67, 97.77 and
      99.57 cGy respectively. Similarly the measured absorbed dose with TLD was within
      +/- 3% with the planned dose for universal wedge (UW) and MW. From the
      experimental measurements, it was found that there was no significant
      contribution of transit dose during MW treatment. CONCLUSION: The actual
      measurements carried out with ion chamber in Equinox-80 machine for UW and MW
      revealed no variation between the doses delivered. The doses were comparable for
      both UW and MW treatments. The results from TLD measurements additionally
      confirmed no variation between the doses delivered with UW and MW. It was also
      demonstrated that the observed excess or less transit dose with MW does not have
      any significant clinical impact. This assured the safe dose delivery with MW.

PMID- 18079576
TI  - Salvage abdominal irradiation for refractory non-Hodgkin's lymphoma.
AB  - BACKGROUND: Abdominal irradiation, as a part of treatment, is often ignored in
      the management of refractory non-Hodgkin's lymphoma (NHL). OBJECTIVE: To evaluate
      the efficacy and the toxicity of this approach after failure of chemotherapy.
      MATERIALS AND METHODS: 27 patients with intraabdominal lymphoma underwent salvage
      irradiation between 1982 and 2001. All patients were treated with a Cobalt-60
      machine. The total dose administered to the abdomen was 18-20 Gy at the rate of
      1.5-1.8 Gy per daily fraction, followed by a boost to gross disease up to 20 Gy.
      All patients had previously been heavily pretreated with chemotherapy. Fourteen
      patients, nine with follicular and five with diffuse lymphomas, had primary
      refractory tumors that had never achieved remission. Thirteen patients, six with
      follicular and seven with aggressive tumors, had refractory relapsed tumors after
      achieving one or more complete remissions. RESULTS: The response rate was 77%.
      The median follow-up was 53 months. The 5-year and 10-year survival rates were 25
      and 17%, respectively. The in-field and out-of-field recurrence rates were 22 and
      33%, respectively. Survival rates were significantly better for patients with
      refractory relapse compared to those with primary refractory lymphoma (P < 0.01).
      There was no significant difference in terms of response, recurrence, or survival
      rates between follicular and aggressive types. Out-of-field recurrence occurred
      more frequently in initial stage III and IV disease. Toxic deaths occurred in
      three patients (11%). CONCLUSION: Salvage radiotherapy for refractory abdominal
      NHL is a feasible alternative for both follicular and diffuse subtypes and may
      provide significant palliation and prolongation of survival. It is less effective
      in patients with primary refractory NHL than in those with refractory relapsed
      NHL.

PMID- 18079577
TI  - Treatment outcome and cost-effectiveness analysis of two chemotherapeutic
      regimens (BEP vs. VIP) for poor-prognosis metastatic germ cell tumors.
AB  - BACKGROUND: In patients with small-volume disseminated disease of germ cell
      tumors, cure can be achieved with four cycles of bleomycin, etoposide, and
      cisplatin (BEP). However, around 20% of these cases are not curable. Strategies
      to improve cure rates have shown that none of the currently available modalities
      were superior to the others. Among the most used ones, BEP and VIP (etoposide,
      cisplatin, and ifosfamide) have been the most studied. However, there are no
      reports comparing the two, except for a few in abstract forms from southern
      India. Therefore, we did a treatment outcome and cost-effectiveness analysis of
      two chemotherapeutic regimens (BEP vs VIP) that are used in poor-prognosis
      metastatic germ cell tumors. MATERIALS AND METHODS: All male patients with germ
      cell tumors, diagnosed as having poor risk by IGCCCG, between January 2002 and
      December 2004 were included in the study. Clinical, laboratory, and other data
      were recorded. The patients were stratified into two categories on the basis of
      the type of chemotherapeutic regimen they received. RESULTS: In all, 46 patients
      were analyzed, with a median follow up of 26.6 months. The baseline
      characteristics (age, stage, PS, histology, and serum markers) were not different
      in the two treatment arms. There is no significant difference in the outcome with
      either of the chemotherapeutic modalities. VIP is less cost effective and more
      toxic compared to BEP. CONCLUSION: In view of the greater toxicity and cost of
      therapy, as well as lack of either overall or disease free survival advantage,
      VIP is not a preferred option for patients with high-risk germ cell tumors in the
      Indian setting and it is still advisable to treat patients with BEP.

PMID- 18079578
TI  - Synchronous dual malignancy: successfully treated cases.
AB  - The occurrence of a second malignancy in a patient with a known malignant tumour
      is not uncommon. Synchronous primary malignancies are still unusual We are
      presenting two cases treated successfully at our centre. Case report 1-A 70 year
      old female presented to us with lump in right breast for two years and bleeding
      per vaginum for two years. Histopathology of cervix showed squamous cell
      carcinoma (large cell non keratinizing) and clinical stage was IIIB. HPE
      mastectomy specimen showed infiltrating duct carcinoma and stage II. Patient was
      treated with external beam radiotherapy for carcinoma cervix and breast
      simultaneously and chemotherapy as required. Patient is on regular follow up and
      clinically no evidence of disease. Case Report 2 -A 40 year old female presented
      with mild headache off and on for one year, projectile vomiting for three months
      and right side facial swelling for three months. HPE brain tissue showed
      astrocytoma grade II and HPE parotid tumour showed low grade muco-epidermoid
      carcinoma. Patient was treated with surgery first then radiotherapy. Patient is
      in regular follow up,having no complain,clinically no neurological dysfunction
      and no evidence of disease at right parotid and neck region. Thus it was
      concluded that patients responded well to treatment. Treatment strategies in case
      of synchronous double malignancy depend on treating the malignancy that is more
      advanced first or sometimes both could be treated simultaneously. In our case we
      concluded that synchronous double malignancy may be treated successfully. Both
      sites should be treated fully as if they were occurring separately considering
      toxicities.

PMID- 18079579
TI  - Brain metastases from breast cancer: management approach.
AB  - Brain metastases are a significant cause of morbidity and mortality in patients
      with breast cancer. HER-2 positivity is an increasingly recognized risk factor
      for the development of brain metastases. Although considerable progress has been
      made in the treatment of this complication, supportive measures like steroids,
      anti-seizure medication and whole-brain radiation remain the cornerstones of
      management in the majority of patients. The current review discusses the above
      and other issues like surgical excision, stereotactic radiotherapy, adjuvant
      radiation, radiosensitization and chemotherapy. A brief discussion of the recent
      evidence for the use of 'HER-1/ HER-2'-targeted therapy is also present.

PMID- 18079580
TI  - Can pomegranate prevent prostate cancer?

PMID- 18079581
TI  - Serum total glutathione-s-transferase levels in oral cancer.
AB  - We conducted a study wherein serum total glutathione-s-transferase levels were
      measured in patients (n = 27) with various stages of biopsy proven oral cancer
      (squamous cell carcinoma) and age and sex matched healthy human volunteers
      (n=10). In all patients with oral cancer, serum total glutathione-s-transferase
      was measured before the onset of treatment. There was a significant increase in
      serum total glutathione-s-transferase levels in patients with stage IV oral
      cancer as compared to stage II (P = 0.001) and stage III (P = 0.002) oral cancer.
      This shows that alterations in serum total Glutathione-s-transferase levels may
      have a role in cancer progression.

PMID- 18079582
TI  - Transient asymptomatic bradycardia in patients on infusional 5-fluorouracil.
AB  - The incidence of 5-fluorouracil (5-FU)-related cardiotoxicity seems to be dosage
      and schedule dependent. Although various other cardiac events have been reported
      in literature, a series of patients having transient asymptomatic bradycardia has
      not been reported in the literature as yet. We report such a series of patients
      who had transient asymptomatic bradycardia after being treated with continuous
      infusion 5-FU. We plan to do a Holter study during the period of bradycardia in
      subsequent patients and this may throw more light on the issue.

PMID- 18079583
TI  - Synchronous malignancies of breast and thyroid gland: a case report and review of
      literature.
AB  - The relationship and coincidence of breast cancer with thyroid disorders is a
      subject of extensive debate and controversy. Many studies have shown that thyroid
      diseases are common among women with breast cancer. We present a case of
      concomitant malignancy of breast and thyroid with review of literature on the
      association of breast with thyroid neoplasm. The potential association and
      plausible mechanisms of breast carcinoma development after or before the thyroid
      carcinoma should be evaluated in larger cohorts of patients.

PMID- 18079584
TI  - A qualitative and quantitative electron microscopic study of differences in
      adrenomedullary adrenaline cells between golden hamsters and rats, with special
      reference to the Golgi apparatus.
AB  - Ultrastructural features of adrenomedullary adrenaline (A) cells in golden
      hamsters and rats were investigated qualitatively and quantitatively with special
      reference to the Golgi apparatus. The A cells displayed a characteristic
      follicular arrangement, with each cell showing structural polarity in hamsters,
      but not apparently in rats. In hamsters, the Golgi apparatus of A cells was
      larger (t-test: P<0.001) and more frequently showed large and complexly organized
      structures (chi(2)-test: P<0.005) compared with that of rats. Quantitative
      analysis of the Golgi apparatus revealed differences in the size and numerical
      density of Golgi vesicles in relation to the animal species and region. Two-way
      analysis of variance (ANOVA) confirmed species difference in the size of coated
      vesicles (P<0.005) and interaction between species and region concerning the size
      of smooth-clear vesicles (P<0.01) and numerical density of granular vesicles
      (P<0.05). One-way ANOVA revealed regional differences in the size and numerical
      density of smooth-clear vesicles in rats and hamsters (P<0.01 approximately
      0.001), and in the numerical density of coated vesicles in hamsters (P<0.05).
      Data were further analyzed by Tukey-Kramer's method. These and other reported
      results suggest that, in hamster A cells, the Golgi apparatus has different
      structural, molecular, and functional mechanisms which are at least partly
      related to the distinct cellular polarity and higher concentration of peptide
      hormones in secretory vesicles, and that in rat A cells, in contrast, loading
      secretory vesicles with A during the post-Golgi stage is predominant. In
      conclusion, the Golgi apparatus in hamster A cells shows markedly different
      ultrastructural features compared with that in rat A cells.

PMID- 18079585
TI  - Interstitial cells of Cajal in the gastrointestinal musculature of W mutant mice.
AB  - Interstitial cells of Cajal (ICC) are important regulatory cells generating
      electrical rhythmicity and transducing neural signals in the gastrointestinal
      musculature. ICC express the proto-oncogene c-kit, a receptor tyrosine kinase,
      and can be examined morphologically using the c-Kit antibody. The c-kit gene is
      allelic with the murine white-spotting locus W, and the c-kit mutation (W
      mutation) affects various aspects of hematopoietic cells, germ cells,
      melanocytes, mast cells, and ICC. Heterozygous W/W( v) mutant mice lack a
      specific type of ICC and have been used to reveal its function. To search for a
      new model that lacks a specific type of ICC, we examined homozygous W( v)/W( v)
      black-eyed-white mice that are viable with anemia. Results showed the principal
      patterns of ICC deficiency were the same between the W/W( v) and W( v)/W( v)
      mutants. In the stomach of both mice, intramuscular ICC (ICC-IM) were missing and
      myenteric ICC (ICC-MY) were reduced in number. In the small intestine, the number
      of ICC-MY was severely reduced in spite of a normal distribution of deep muscular
      plexus ICC (ICC-DMP). The cecum also exhibited fewer reduced. ICC-IM in the colon
      were almost entirely missing, whereas ICC-MY were reduced only in the distal
      colon. In the small intestine and colon, the number of remaining ICC-MY in W(
      v)/W( v) mice was greater than that in W/W( v) mice. The enteric nervous system
      of the two mutant mice showed normal characteristics. From these findings, we
      conclude that W( v)/W( v) mice represent a new genotype that lacks a part of the
      ICC in its gastrointestinal musculature.

PMID- 18079586
TI  - Age-related changes in the microarchitecture of collagen fibrils in the articular
      disc of the rat temporomandibular joint.
AB  - The microarchitecture of collagen fibrils in the articular disc of the
      temporomandibular joint (TMJ) plays an important role in dissipating the
      mechanical load during jaw movement. However, little information is available on
      its adaptations to the biomechanical environment during development. To address
      this issue, we analyzed the diameter of collagen fibrils of the articular disc of
      the rat TMJ with quantitative ultrastructural analysis during postnatal
      development. The mean diameter of the collagen fibrils significantly increased
      and the arrangement of the collagen fiber networks became compact during
      development. Articular discs of suckling rat pups were composed of thin,
      uniformly sized collagen fibrils (range: 30-60 nm, peak: 40-50 nm). At the age of
      4 weeks, thicker collagen fibrils began to appear in articular discs, shortly
      after weaning (range: 20-70 nm, peak: 40-50 nm). In articular discs of adult
      rats, collagen fibrils varied widely in diameter, with thick fibrils
      predominating (range: 10-120 nm, peak: 40-70 nm). These age-related changes in
      the microarchitecture of collagen fibrils in articular discs may reflect changes
      in their biomechanical environment during development.

PMID- 18079587
TI  - Immunohistochemical features of substance P-immunoreactive chromaffin cells and
      nerve fibers in the rat adrenal gland.
AB  - The distribution of substance P (SP) immunoreactivity and the colocalization of
      SP with other bioactive substances in chromaffin cells and nerve fibers were
      investigated in the rat adrenal gland at the light microscopic level. In the
      capsule and cortex, SP immunoreactivity was seen in some nerve fibers around
      blood vessels and in thick nerve bundles passing through the cortex directly into
      the medulla. In the medulla, the SP immunoreactivity was observed in a small
      number of chromaffin cells; these SP-immunoreactive chromaffin cells were either
      phenylethanolamine N-methyltransferase (PNMT) immunoreactive or immunonegative,
      indicating that they were either adrenaline cells or noradrenaline (NA) cells. SP
      immunoreactive varicose nerve fibers were also found in the medulla and were in
      contact with a cluster of the NA cells showing catecholamine fluorescence, which
      suggests that SP from medullary nerve fibers may regulate the secretory activity
      of the NA cells. Because no SP-immunoreactive ganglion cell was present in the
      rat adrenal gland, the intra-adrenal nerve fibers were considered to be extrinsic
      in origin. The double-immunostaining method further revealed that the SP
      immunoreactive chromaffin cells also exhibit immunoreactivities for calcitonin
      gene-related peptide (CGRP), and neuropeptide tyrosine (NPY), suggesting that
      these peptides can also be released from the chromaffin cells by certain stimuli.
      The intra-adrenal nerve fibers in the medulla were composed of SP-single
      immunoreactive, and SP/CGRP-, SP/choline acetyltransferase (ChAT)-, SP/nitric
      oxide synthase (NOS)-, SP/pituitary adenylate cyclase activating polypeptide
      (PACAP)-, ChAT/NOS-, and ChAT/PACAP-immunoreactive nerve fibers, which may affect
      the secretory activity of the NA cells. In the adrenal capsule, the nerve fibers
      were present around blood vessels and showed immunoreactivities for SP/ CGRP,
      SP/NPY, SP/NOS, and SP/vasoactive intestinal polypeptide, suggesting that the
      origin of nerve fibers in the capsule may differ from those in the medulla.

PMID- 18079588
TI  - Hypothermic, but not normothermic, ischemia causes a drastic increase in
      cyclooxygenase-2 immunoreactive granule cells in rat dentate gyrus after 4 hours
      of ischemic reperfusion.
AB  - We investigated cyclooxygenase-2 (Cox-2) immunoreactive cells in the hippocampus
      and dentate gyrus of Sprague-Dawley rats at 4 h after the induction of
      normothermic and hypothermic ischemia and reperfusion. Under the normothermic
      condition, Cox-2 immunoreactive cells showed more intense staining and clearer
      proximal dendrite configurations as compared with the control animals, whereas
      the numbers of immunoreactive cells in the hippocampus and dentate gyrus were not
      remarkably increased. In contrast to the normothermic condition, long-term (pre-
      and intra-ischemic) and short-term (exclusively intra-ischemic) hypothermic
      conditions caused a drastic increase in immunoreactive cells in the dentate
      gyrus. Nearly all granule cells were immuno-positive for Cox-2, whereas the CA3
      and hilus sectors showed no remarkable increase in immunoreactive cell numbers.
      In sham-operated animals exposed to long-term hypothermia - but not ischemia, Cox
      2 staining profiles were similar to those in the control animals. These results
      suggest that, for a drastic increase in Cox-2 immunoreactive granule cells to
      occur within a short time period (4 h), at a minimum, both hypothermia and
      ischemia, are required. Considering the neuroprotective roles of the hypothermia,
      a rapid increase in Cox-2 in the dentate gyrus might be associated with this
      temperature-sensitive phenomenon.

PMID- 18079589
TI  - A possible monosynaptic pathway links the pedunculopontine tegmental nucleus to
      thalamostriatal neurons in the hooded rat.
AB  - The thalamic lateral posterior nucleus (LP) of the hooded rat is regarded as a
      relay nucleus for the transmission of information from visuomotor-related
      structures such as the superior colliculus, pedunculopontine tegmental nucleus
      (PPT) and substantia nigra, pars reticulata, to visual cortical areas as well as
      the striatum. The aim of the present study was to examine the relationships of
      the thalamo-striatal projection neurons with the LP afferent fibers derived from
      the PPT, using injections of the anterograde tracer biotinylated dextran amine
      (BDA) and the retrograde tracer cholera toxin-B (CTB) into the PPT and the
      striatum, respectively. Findings showed that the location of terminals derived
      from PPT and LP neurons projecting to the striatum overlapped considerably in the
      ventral portion of the LP. Ultrastructural observations within this overlapped LP
      region showed that BDA-labeled terminals make synaptic contacts with dendrites of
      CTB-labeled neurons. The present results thus provide morphological support for
      the contention that information from the PPT neurons is relayed to the striatum
      through by the LP.

PMID- 18079590
TI  - Relationship between metabolic syndrome categorized by newly recommended by
      International Diabetes Federation criteria with plasma homocysteine
      concentration.
AB  - Plasma total homocysteine (tHcy) is an independent risk factor for cardiovascular
      disease and increased tHcy levels have been reported to be a novel risk factor of
      atherosclerotic disease. The aim of this study was to assess the association of
      the metabolic syndrome components with plasma (tHcy) level. Total 722
      participants (284 men, 438 women) from the medical checkup program were enrolled
      in this study. The clinical characteristics and biochemical parameters of the
      subjects were assessed and the tHcy levels were compared according to the
      components of metabolic syndrome diagnosed by Adult Treatment Panel (ATP) III
      guideline and International Diabetes Federation (IDF) criteria. Among the
      components, groups with larger waist circumference and higher fasting blood
      glucose levels showed significantly higher tHcy level than the counterparts.
      Although statistically insignificant, mean concentrations of tHcy was higher in
      subjects with metabolic syndrome defined by both criteria. In multiple regression
      analysis, age, sex and systolic blood pressure were the independent determinants
      of tHcy level. In conclusion, tHcy level was not associated with metabolic
      syndrome defined by either criteria in Korean subjects.

PMID- 18079591
TI  - Expression of adrenocorticotropic hormone, prolactin and transcriptional factors
      in clinically nonfunctioning pituitary adenoma.
AB  - We describe here a case of a clinically nonfunctioning pituitary adenoma, but
      with expression of ACTH and PRL. A 42-year-old woman was referred to our
      department for further evaluation of pituitary tumor. She had no acromegaloid
      features, and no typical Cushingoid features. She had no galactorrhea, and had
      regular menses. GH, IGF-I, LH, FSH, TSH, ACTH and cortisol levels in blood were
      all within the normal ranges, while PRL levels were mildly elevated. Both ACTH
      and cortisol levels were adequately increased in response to CRH, and both were
      suppressed by a small dose of dexamethasone. Plasma ACTH and cortisol levels were
      decreased at night, suggesting the circadian rhythms for plasma ACTH levels were
      undisturbed. Based on these findings we did not clinically suspect ACTH-producing
      tumor, however immunohistochemistry revealed ACTH immunoreactivity in the
      pituitary adenoma. Therefore, the tumor was considered a silent corticotroph
      adenoma. PRL was co-expressed in a significant subpopulation of ACTH
      immunoreactive tumor cells. Ptx1, Neuro D1, and T pit were densely expressed and
      Pit-1 was sparsely expressed in the nuclei of adenoma cells. It is therefore
      possible that a tumor originating in an immature or uncommited adenohypophysial
      stem cell may later differentiate into different cell types due to a combination
      of certain specific transcriptional factors.

PMID- 18079592
TI  - Structure, function, and regulated expression of neurotransmitter transporters.

PMID- 18079593
TI  - Monoamine transporter as a target molecule for psychostimulants.

PMID- 18079594
TI  - Role of glutamate transporters in brain development.

PMID- 18079595
TI  - Antinociceptive effects of glycine transporter inhibitors in neuropathic pain
      models in mice.

PMID- 18079596
TI  - [Pathophysiology and treatment of depression: a review of PET imaging of
      serotonin transporter.

PMID- 18079597
TI  - Effects of mood stabilizer on the circadian system: possible implication for
      abnormalities in mood disorders.

PMID- 18079598
TI  - Current studies on neuronal death and neurodegenerative diseases.

PMID- 18079599
TI  - Development of experimental allergic rhinitis model using Japanese cedar pollen.

PMID- 18079600
TI  - Basic research for Alzheimer's disease drugs.

PMID- 18079601
TI  - Practical clinical use of therapeutic agents for Alzheimer's disease.

PMID- 18079602
TI  - What is ICH? - Current status of non-clinical safety guidelines.

PMID- 18079603
TI  - Current status and view of the alternatives to animal testing.

PMID- 18079604
TI  - Dietary sesame seed and its lignan increase both ascorbic acid concentration in
      some tissues and urinary excretion by stimulating biosynthesis in rats.
AB  - We previously showed that the intake of sesamin, a major lignan in sesame seed,
      decreased lipid peroxidation and elevated tocopherol concentration in rat
      tissues. In this study, we examined the effect of dietary sesame seed and sesamin
      on the ascorbic acid concentration in rat tissues. Rats (4-wk-old) were fed
      either a vitamin E-free diet, or a diet containing 50 mg gamma-tocopherol/kg, one
      containing 2 g sesamin/kg, one containing 50 mg gamma-tocopherol/kg and 2 g
      sesamin/kg, or one containing 200 g sesame seed/kg for 28 d. The dietary sesamin
      and sesame seed elevated ascorbic acid concentrations in the liver and kidney,
      and increased urinary excretion in those Wistar rats. The dietary sesamin also
      elevated the hepatic mRNA levels of cytochrome P450 (CYP) 2B, and UDP
      glucuronosyltransferase (UGT) 1A and 2B. In contrast, neither the sesamin nor the
      sesame seed affected the liver concentration of ascorbic acid in ODS rats with a
      hereditary defect in ascorbic acid synthesis, though the dietary sesame seed
      elevated the UGT1A and 2B mRNA levels in the liver. In addition, the sesame seed
      elevated the gamma-tocopherol concentration in the various ODS rat tissues and
      the ascorbic acid concentrations in the kidney, heart and lung, while reducing
      the thiobarbituric acid reactive substance concentration in the heart and kidney.
      These results suggest that dietary sesame seed and its lignan stimulate ascorbic
      acid synthesis as a result of the induction of UGT1A and the 2B-mediated
      metabolism of sesame lignan in rats. The data of ODS rat studies also suggest
      that dietary sesame seed enhances antioxidative activity in the tissues by
      elevating the levels of two antioxidative vitamins, vitamin C and E.

PMID- 18079605
TI  - Hydroxymatairesinol and sesaminol act differently on tocopherol concentrations in
      rats.
AB  - We have previously reported that sesame seed with the tetrahydrofurofuran type
      lignans sesamin and sesaminol (SeOH) produced higher tocopherol concentrations,
      while flaxseed with the dibenzylbutyrolactone type lignans did not cause higher
      tocopherol concentrations in rats. Sesame seeds also contain the
      dibenzylbutyrolactone type lignan 7-hydroxymatairesinol (HMR). To clarify whether
      or not the tocopherol elevating effect is affected by the chemical structure of
      lignans, the effect of HMR isolated from Norway spruce, was compared with SeOH,
      isolated from sesame seed. The lignans were added to a low alpha-tocopherol (10
      mg/kg) diet, and rats were maintained on these diets for 8 wk. The experimental
      diet containing 0.2% SeOH elevated alpha-tocopherol content in the plasma liver,
      kidney, and brain, but HMR (0.2% or 0.5%) had no effects. Dietary HMR and SeOH
      (both in concentrations of 0.2%) were further compared in rats fed on a gamma
      tocopherol (50 mg/kg) containing diet. SeOH produced significantly higher g
      tocopherol content in the plasma and tissues, and significantly lower 2,7,8
      trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC, a gamma-tocopherol
      metabolite) content in the urine. However, HMR did not show such effects. These
      results suggest that the sesame lignan SeOH increases tocopherol concentrations
      in animals by suppressing the conversion of gamma-tocopherol to gamma-CEHC. HMR,
      a structurally different plant lignan, does not have such properties. Further
      studies are needed to show the potential health effects associated with an
      increased tocopherol concentration in the body.

PMID- 18079606
TI  - Beneficial effect of 3% milled-rice on blood glucose level and serum lipid
      concentrations in spontaneously non-insulin-dependent diabetic rats.
AB  - Three percent milled-rice was evaluated for beneficial effect on blood glucose
      level and serum lipid concentrations in an experiment with Otsuka Long-Evans
      Tokushima Fatty (OLETF) rats, used as model animals for spontaneously non-insulin
      dependent diabetes mellitus. The same experiment was carried out using Long-Evans
      Tokushima Otsuka (LETO) rats, the control of the OLETF rats. The results obtained
      from the rats given a diet containing 3% milled-rice (3% MRD) ad libitum were
      compared with those from rats given polished rice. During the feeding period of
      140 d, body weight of the OLETF rats receiving the 3% MRD was significantly lower
      than that of the rats fed on the diet containing polished rice (PRD) from the
      48th to the 124th days. The body weight of the LETO rats during the both periods
      of 90 to 104 d and 114 to 140 d was lower than that of the rats receiving the
      PRD. Though food intakes of the rats receiving 3% MRD were significantly lower in
      the OLETF and LETO rats during the two periods of days 48 to 124 and days 1 to
      140 than in the rats of the PRD group, the feed efficiency of the OLETF or LETO
      rats did not show significant difference between the 3% MRD and the PRD groups
      during the same experimental periods. The excretion rate of feces of the OLETF
      rats receiving the 3% MRD was significantly higher than that of the rats
      receiving the PRD, both on the 126th day and during the period of days 129 to
      131. The fasting blood glucose levels were significantly lower in the OLETF rats
      receiving the 3% MRD than the rats receiving the PRD on the 84th day, the 105th
      day and the 127th day, and also lower in the LETO rats receiving the 3% MRD on
      the 84th day and the 105th day. The incremental areas under the curve of blood
      glucose concentrations (IAUC-Glc) for 120 min after oral administration of
      glucose on the 133rd day was lower in the OLETF rats receiving 3% MRD than that
      of the PRD. The ratio of IAUC-Glc in the 3% MRD to PRD group, after ingestion of
      diets for 1 h after fasting for 18 h on the 138th day, was 0.89 in the OLETF
      rats, and 0.74 in the LETO rats. Compared with the PRD group, the amounts of
      cholesterol and bile acid in the feces of the OLETF rats in the 3% MRD group were
      significantly higher on days 129-131, and the cholesterol excretion was
      significantly higher on the 84th day in the OLETF rats in the 3% MRD group. The
      liver weight, the level of total lipids in liver, and the concentrations of
      triglyceride and total cholesterol in liver and serum of the OLETF rats on the
      140th day were significantly lower in the 3% MRD than those of the PRD group.
      These results indicate that 3% milled-rice has beneficial effects on blood
      glucose level and serum lipid concentrations in spontaneously non-insulin
      dependent diabetic rats.

PMID- 18079607
TI  - Effect of protein and energy intakes on body composition in non-diabetic
      maintenance-hemodialysis patients.
AB  - This cross sectional study was performed to find the adequate amount and
      combination of dietary protein and energy for maintaining better nutritional
      status for stable non-diabetic maintenance hemodialysis (MHD) patients. The body
      composition including body fat, total body water, body cell mass and body protein
      were measured by multi-frequency bioelectrical impedance analysis in 200 stable
      MHD patients without diabetes (124 men, 76 women). Dietary energy intake (DEI)
      and dietary protein intake (DPI) were assessed by a brief self-administered diet
      history questionnaire (BDHQ), the DPI value being confirmed by calculating the
      normalized protein equivalent of total nitrogen appearance (nPNA). The
      nutritional status and the body composition were compared among 4 groups of
      patients in each gender that were divided by the combination of DEI and DPI; high
      energy (HE)/high protein (HP), HE/low protein (LP), low energy (LE)/HP and LE/LP
      groups. The mean DPI ranged between 1.17-1.23 and 0.89-0.95 g/kg IBW/d in the HP
      and LP groups, respectively for both genders, and the mean DEI was 35-37 and 24
      25 kcal/kg IBW/d in HE and LE groups, respectively. BMI and serum albumin
      concentration were not different among the 4 groups. Body cell mass index (BCMI)
      was maintained in the HE groups regardless of DPI, and it was significantly
      higher in the HE/HP group than in the LE/LP group. Multiple regression analysis
      also showed that the BCMI was more greatly affected by DEI than DPI. These
      results indicated that a DPI of 0.89-0.95 g/kg IBW/d could be sufficient for
      maintaining BCMI, if DEI is kept over 35 kcal/kg IBW/d in stable non-diabetic MHD
      patients. This DPI level is lower than the recommended DPI proposed by dietary
      guidelines in the US and Japan.

PMID- 18079608
TI  - Nutritional effects of gamma-glutamyl carboxylase gene polymorphism on the
      correlation between the vitamin K status and gamma-carboxylation of osteocalcin
      in young males.
AB  - Vitamin K is a cofactor for gamma-glutamyl carboxylase (GGCX), which is an
      essential enzyme for the gamma-carboxylation of vitamin K-dependent proteins such
      as osteocalcin (OC). Associations among dietary vitamin K intake, vitamin K
      status, and bone metabolism have not been thoroughly investigated. Recently, it
      has been reported that single nucleotide polymorphisms of GGCX (R325Q, 974G>A)
      were associated with age-related bone loss and the kinetic affinity for the
      substrate. In the present study, we investigated the associations among dietary
      vitamin K intake, the level of serum vitamin K, and the ratio of
      undercarboxylated OC (ucOC) to intact OC. The subjects were 60 healthy young male
      volunteers (mean age, 22.6 y; standard deviation, 1.6). Dietary nutrient intake
      was assessed by consecutive individual 3-d food records taken before the day of
      blood examinations. Serum concentrations of vitamin K (phylloquinone: PK,
      menaquinone 4: MK-4, and menaquinone 7: MK-7), ucOC, and intact OC were measured.
      All subjects were genotyped for polymorphism (R325Q) presence. Dietary vitamin K
      intake from vegetables was significantly correlated with the level of serum PK,
      and vitamin K intake from fermented beans, natto, was also significantly
      correlated with the level of serum MK-7. The ratio of ucOC to intact OC showed a
      negative association with the total vitamin K intake (r=-0.331, p=0.010) and
      serum MK-7 (r=-0.394, p=0.002). Interestingly, grouped by the GGCX genotype, a
      significant interaction between the ratio of ucOC to intact OC with serum MK-7
      was observed in 325R homozygotes (r=-0.572, p=0.003), but not in heterozygotes,
      nor in 325Q homozygotes. This is the first report to suggest the effects of the
      single nucleotide polymorphism R325Q in the GGCX gene on the correlation between
      the level of serum MK-7 and gamma-carboxylation of serum OC.

PMID- 18079609
TI  - Nutritional and hormonal regulation of uncoupling protein gene expression in rat
      adipocytes.
AB  - Nutritional and hormonal regulation of the expression of uncoupling protein (UCP)
      1, -2, and -3 mRNA and protein was investigated in primary cultured adipocytes of
      rats. The UCP-1, -2, -3 mRNA and protein induction in the adipocytes reached
      maximal levels at 4 h in the presence of glucose with or without insulin.
      Moreover, the UCP induction was accelerated by triiodothyronine (T3) or
      epinephrine, and reached a maximum at 2 h. It appeared that the induction of UCP
      mRNA and protein was rapid. UCP-1 mRNA expression was stimulated by the presence
      of T3 or epinephrine in the culture medium. UCP-2 mRNA expression was more
      markedly increased by glucose, unsaturated fatty acids, insulin and T3 than UCP-1
      or -3 mRNA expression. UCP-3 expression was more markedly increased by
      epinephrine than by T3. The protein expression of the UCPs was induced by glucose
      and the hormones nearly parallel to the UCP mRNA expression. Thus, UCP-2
      expression appears to be stimulated by energy sources such as glucose and fat,
      and by regulators of thermogenesis and basal metabolic rate such as T3 and
      insulin, in contrast to UCP-1 and -3 expression.

PMID- 18079610
TI  - Retinoic acid inhibits uterotrophic activity of bisphenol A in adult
      ovariectomized rats.
AB  - Bisphenol A (BPA) is used in the production of polycarbonate and epoxy resins.
      The weak estrogenic activity of BPA has been confirmed by both in vitro and in
      vivo assays. Retinal acetate has been reported to inhibit the adverse effects of
      BPA on male mice reproduction. All-trans-retinoic acid (ATRA) is a potent natural
      derivative of vitamin A and is reported to inhibit the estrogen-induced
      proliferation of human breast carcinoma cells. In this study, we investigated the
      possible inhibitory effects of ATRA on the estrogenic activity of BPA by a
      standard in vivo uterotrophic assay. Proliferated and apoptotic uterine cells
      were identified by 5-bromo-2'deoxyuridine (BrdU) incorporation and terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay.
      We observed that ATRA supplementation significantly inhibits a BPA-induced
      uterine weight increase in adult ovariectomized rats. However, there were no
      significant differences in the increases in the numbers of BrdU-positive cells
      and TUNEL-positive cells between the BPA and BPA+ATRA groups. These results show
      that ATRA may have an inhibitory effect on the estrogenic activity of BPA in an
      in vivo assay.

PMID- 18079611
TI  - Survey on the implementation of blood and urine examinations at Japanese
      institutions and schools for individuals with intellectual disabilities and/or
      motor disabilities in 1998.
AB  - OBJECTIVES: Few national surveys have been conducted on the health and nutrition
      of disabled people in Japan, and as a result, the actual health and nutritional
      status of this population group has not been clarified. The aim of the present
      study is to clarify the following hypotheses: nutritional assessment is not
      carried out at institutions and schools for individuals with intellectual
      disabilities (ID) and/or motor disabilities (MD), and there are marked
      differences in implementation rates and assessment methods (i) between
      institutions and schools and (ii) among the disability categories. METHODS:
      Questionnaires were sent to 1,080 selected institutions and schools for
      individuals with ID and/or MD. For each disability category, the implementation
      rate of blood and urine tests (14 items) was calculated separately for the
      institutions and schools. RESULTS: A total of 826 responses were obtained
      (response rate: 76.5%); of these, 822 were valid. For all investigated items,
      implementation rate was significantly higher for the institutions (0-90.3%) when
      compared to the schools (0-10.2%). The implementation rate of 13 items at
      institutions for patients with severe intellectual and motor disabilities (4.8
      90.3%) was higher than that for institutions for those with intellectual
      disabilities (0.4-57.0%) or institutions for those with motor disabilities (0
      80.0%). The implementation rate of creatinine urinary excretion/24 h and
      creatinine height index was lower than that for other examinations. CONCLUSIONS:
      Large differences in implementation rates were apparent between the institutions
      and schools. The implementation rate of blood and urine laboratory examinations
      varied considerably among the disability categories.

PMID- 18079612
TI  - Effects of nerve growth factor and dimethylsulfoniopropionate in green sea algae
      on the outgrowth of neurites from pheochromocytoma cells.
AB  - The effects of various concentrations of the nerve growth factor (NGF) and of
      dimethylsulfoniopropionate (DMSP) on the outgrowth of neurites from
      pheochromocytoma (PC12) cells were examined singly or in combination on an RPMI
      1640 medium containing 10% horse serum, 5% fetal bovine serum, penicillin and
      streptomycin in collagen-coated Petri dishes by increasing the incubation times
      up to 4 d. The results indicated that NGF significantly accelerated the number of
      neurite-bearing cells, which reached a maximum at concentrations of more than 0.5
      ng/mL among the various concentrations of NGF on the 4th day. The combined
      effects of the various concentrations (10(-6)-10(-3) M) of DMSP with NGF (5
      ng/mL) on the growth and the number of neurite-bearing cells were then examined,
      which demonstrated that all the concentrations of DMSP restricted the growth of
      the cells to various extents but that the concentration of DMSP at 10(-4) M with
      the NGF more highly accelerated the number of neurite-bearing cells than did the
      NGF alone during the experimental period.

PMID- 18079614
TI  - Protease-resistant fraction of smoked, dried bonito alleviates atopic dermatitis
      like skin lesions in NC/Nga mice.
AB  - The effect of smoke-dried bonito undigested fraction remaining after microbial
      protease treatment (SDBR) on a spontaneously occurring mouse model of atopic
      dermatitis was studied in male 5-wk-old, NC/Nga mice. Smoke-dried bonito,
      Katsuobushi, is a traditional Japanese food. SDBR contains 2 major components:
      bonito oil and protease-undigested proteins. Mice were fed a casein diet
      containing corn oil (C diet) or a diet containing SDBR (SDBR diet) for 18 wk. In
      comparison with the C diet, the SDBR diet alleviated the increase in skin
      severity score and plasma IgE concentration in a time-dependent manner, and
      lowered leucotriene B(4) (LTB(4))-releasing ability upon calcium ionophore A23187
      stimulation. The SDBR diet did not affect scratching time. These results
      demonstrate that SDBR diet alleviates atopic dermatitis-like skin lesions in
      NC/Nga mice.

PMID- 18079613
TI  - Effect of dietary fiber in edible seaweeds on the development of D-galactosamine
      induced hepatopathy in rats.
AB  - Previous studies in our laboratory demonstrated the repressive effect of seaweeds
      (Laminaria sp., Sargassum fulvellum, Eisenia bicyclis and Gelidium sp.) against D
      galactosamine (D-GalN)-induced hepatopathy. However, the mechanism by which these
      four seaweeds attenuate the D-GalN-hepatopathy has not been completely clarified.
      This study was carried out to determine the constituents of these seaweeds that
      protect rats against the D-GalN-hepatopathy. Male Wistar rats were fed for 8 d
      diets containing 5% seaweeds with or without the antibiotic neomycin (NEO) in
      experiment 1, and typical seaweed dietary fibers (laminaran, fucoidan, alginate,
      agar and kappa-carrageenan) of these seaweeds in experiment 2. On the 7th day,
      the rats were treated with D-GalN (1,900 mg in experiment 1 and 800 mg/kg in
      experiment 2) and then sacrificed 24 h after the injection of D-GalN. Their serum
      transaminase (aspartate and alanine aminotransferases: AST and ALT) activities
      were then determined. In experiment 1, the serum AST and ALT levels in the rats
      fed the four kinds of seaweeds without NEO were significantly low in comparison
      to that of the control group, but those with NEO were not significantly different
      among the groups. In experiment 2, the serum AST and ALT levels in the rats fed
      fucoidan were significantly low in comparison to those of the other groups fed
      the dietary fibers and the control. These results suggest that the protective
      effect of the three kinds of brown seaweeds Laminaria sp., Sargassum fulvellum
      and Eisenia bicyclis against D-GalN-hepatopathy was caused at least in part by
      fucoidan.

PMID- 18079615
TI  - [Is it possible to make a diagnosis of cancer by smelling?].
AB  - It had been reported that a house dog could make notify the dog's owner to have
      malignant melanoma through sniffing intently and trying to bite off a pigment
      lesion on the thigh of its owner. This fact resulted in extensive study of
      training dogs to distinguish the special odour of exhaled breath or urine of
      patients with cancer from those of the healthy subjects. These studies have
      promoted further development of detecting and identifying the special odour
      substances excreted from the patients with cancer using Gas chromatography-Mass
      spectrometry (GC-MS) technique and further expanded to the exploitation of the
      electronic noses. Here, the authors made a brief general survey on these
      progressions. Though the field of electronic noses has made a great progress in
      recent years, there remain many difficulties in predicting cancer with excellent
      accuracy. We hope that there should be a breakthrough in this field and every
      clinic could obtain a useful instrument at a moderate price and, in the near
      future, could predict with high reliability whether a patient has cancer or not.

PMID- 18079616
TI  - [Acute myeloid leukemia].
AB  - The heterogeneity of acute myeloid leukemia (AML) has been established by many
      new insights from molecular biological studies. In AML with favorable cytogenetic
      changes, KIT gene mutation has been known as a worse prognostic marker. Even in
      AML with normal cytogenetics, numerous molecular genetic alterations have been
      identified including internal tandem duplication of the FLT3 gene (FLT3-ITD),
      mutations in the NPM1 gene, mutations in the CEBPA gene, and partial tandem
      duplication of the MLL gene. Of these, FLT3-ITD has the most important prognostic
      implication. Insights into the molecular pathogenesis of AML have led to the
      development of more specific targeted agents. Currently, a number of agents have
      been explored in AML, including immunoconjugate of anti-CD33 antibody and
      cytotoxic agent (gemtuzumab ozogamicin: GO), tyrosine kinase inhibitors and
      farnesyl transferase inhibitor. These agents have shown promise in small studies.
      Large phase III studies will reveal whether these are effective in inducing
      complete remission and prolonging survival. Combining targeted agents with each
      other or with chemotherapy may improve the response rates. GO is the most
      promising drug, which has been evaluated in randomized trials by several major
      cooperative groups to determine whether the addition of GO improves the complete
      remission rate and overall survival. In the near future AML may be classified and
      treated by their molecular biological alterations.

PMID- 18079617
TI  - [Acute lymphoblastic leukemia (ALL)].
AB  - In the past few decades, the results of treatment for childhood acute
      lymphoblastic leukemia (ALL) have achieved about 80% long-term disease-free
      survival (DFS). Although the complete remission (CR) rate of adult ALL has also
      improved from 70 to 90%, 5-year overall survival (OS) remains only about 30%
      because of the high incidence of relapse. Especially, the disease with
      Philadelphia chromosome-positive (Ph+) ALL has been considered to have a poor
      prognosis. Recently, the selective inhibitor of BCR-ABL kinase, imatinib, showed
      significant efficacy in the treatment of Ph+ALL, and imatinib-combined
      chemotherapy for Ph+ALL is expected to improve the prognosis of this disease. At
      the same time, resistance to imatinib, resulting in relapse, is also reported.
      Once the patient relapses, subsequent cure becomes unlikely. The current
      available treatment to prevent recurrence of the disease is allogeneic
      hematopoietic transplantation (HST), if there is an HLA-matched donor. In Ph
      negative (Ph-) ALL, young adults have superior outcomes with a 5-year OS of 81%
      when treated in pediatric clinical trials. HST may not always be necessary for
      this group of patients. For patients without donor or older than 50, novel
      biologic or targeted therapies are warranted, and early detection of minimal
      residual disease may also change strategies and improve the outcome of this
      disease.

PMID- 18079618
TI  - [An advance in the treatment of CML].
AB  - Imatinib mesylate, a selective inhibitor of the ABL tyrosine kinase, has
      revolutionized the treatment of chronic myelogenous leukemia (CML) due to its
      high level of activity, low toxicity, and durability. Five-year data from the
      pivotal trial of imatinib, the IRIS trial, suggests durable responses in a high
      proportion and reduction and almost elimination of the incidence of imatinib
      failure over time. The imatinib dose of 400 mg is considered to be standard based
      on the IRIS trial. Recently, new tyrosine kinase inhibitors (TKI) have been
      developed, which can overcome imatinib resistance, and comparative studies
      between each TKI and imatinib are ongoing for imatinib-resistant CML and newly
      diagnosed CML. TKI will be chosen based on the profiles of mutation of the ABL
      kinase domain. On the other hand, the results of hematopoietic stem cell
      transplantation in patients treated with imatinib were reported, and pretreatment
      of imatinib did not influence TRM. However, the optimal dose, duration of
      imatinib treatment and the indication of reduced intensity conditioning
      transplantation have not been established. Longer follow-up, the accumulation of
      results of the new TKI therapy and HSCT are required.

PMID- 18079619
TI  - [Current treatment for malignant lymphomas].
AB  - Hodgkin Lymphoma (HL), follicular lymphoma (FL), and diffuse large B cell
      lymphoma (DLBCL) are three of the commonest subtypes of malignant lymphomas.
      Optimal treatments for these lymphomas should be chosen based upon prognostic
      indexes defined internationally and current available best therapeutic
      strategies. For patients with newly diagnosed HL, ABVD as standard chemotherapy
      is chosen in order to cure the disease and to reduce late toxicities such as
      cardiomyopathy and second cancers. Chemotherapy with or without radiotherapy is
      unlikely to cure patients with FL except early or limited disease, although their
      clinical courses are indolent. However, rituximab (RIT), an anti-CD20 monoclonal
      antibody, will improve the outcome of FL since the results of several phase II
      and III trials of RIT alone and in combination with chemotherapy are promising.
      In treatment for newly diagnosed DLBCL, RIT combined with CHOP (R-CHOP) has
      become a current standard initial therapy based upon the superior results of R
      CHOP from phase III studies comparing CHOP to R-CHOP. RCHOP has overcome several
      poor prognostic biomarkers such as BCL-2 and BCL-6 in DLBCL. In addition, novel
      treatment strategies combining RIT and intensive chemotherapy such as EPOCH for
      patients younger than 60 years of age will improve the outcome of these patients
      with poor prognosis of international prognostic index (IPI).

PMID- 18079620
TI  - [Advances in therapeutic strategies for multiple myeloma].
AB  - Multiple myeloma (MM) remains an incurable plasma cell dyscrasia characterized by
      bone marrow failure, bone disease, renal disease and other complications. The
      clinical pictures show extensive diversity which is based on complex cytogenetic
      abnormalities, and lot of interactions between myeloma cell and bone marrow
      stroma. Recently, advances in understanding the biology of myeloma including the
      function of proteasome, molecular chaperons on the folding of intracellular
      proteins as well as signal transduction pathway, apoptosis-inducing cascade and
      oncogenomics, have brought about the development of several new therapeutic
      strategies. This review summarizes the major innovative agents in this field and
      discuss the future directions.

PMID- 18079621
TI  - [Evaluation of combination chemotherapy with S-1 and docetaxel for patients with
      oral squamous cell carcinomas].
AB  - The purpose of this study was to evaluate the effectiveness and adverse events of
      combination chemotherapy with S-1 and docetaxel (DOC) as neo-adjuvant
      chemotherapy (NAC) for patients with oral squamous cell carcinomas. Fifteen
      patients were enrolled in this study (11 men and 4 women, with a mean age of 65.9
      years). All patients given S-1 80 mg/body per day for 14 days and following were
      administered a dose of DOC 60 mg/m(2) by drip infusion for 120 minutes. The
      locoregional response was evaluated 3 weeks after the administration. As a
      result, the locoregional response rate was 60.0%, including 46.7% complete
      response. According to Oboshi and Shimosato's classification, histological
      evaluation of surgical specimens revealed that 3 cases were Grade I , 3 cases
      Grade IIa, 4 cases Grade IIb, 1 case Grade III, 3 cases Grade IVb, and 1 case
      Grade IVc. The severe side effect was neutropenia. The present study suggests
      that combination chemotherapy with S-1 and DOC is an effective and safe regimen
      in NAC for oral squamous cell carcinomas.

PMID- 18079622
TI  - [Evaluation of neoadjuvant chemotherapy with paclitaxel, 5-fluorouracil and
      cisplatin for advanced gastric cancer with pyloric stenosis].
AB  - S-1 is currently recognized as one of the standard treatments for advanced and
      recurrent gastric cancer in Japan. However, there are some patients who can not
      take oral medication due to pyloric stenosis. We performed a critical evaluation
      of neoadjuvant chemotherapy (NAC) with paclitaxel (PTX), 5-fluorouracil (5-FU)
      and cisplatin (CDDP); (PTX+FP) for patients with advanced gastric cancer with
      pyloric stenosis. Since September 2001, 13 patients with far advanced or non
      curative respectable gastric cancer with pyloric stenosis received NAC. These
      patients were treated with paclitaxel 40 mg/m(2) infusions on days 1 and 8,
      combined with CDDP (6.5 mg/m(2)) and 5-FU (350 mg/m(2)) on days 1 through 8
      followed by 2 weeks rest as one course. After at least 2 courses of treatment,
      the patients underwent gastrectomy with lymphadectomy. The overall response rate
      was 38.5% (CR: 0, PR: 5), 7 patients had SD and 1 patient had PD. Seven patients
      had received staging laparoscopy before NAC and 6 patients had free cancer cells
      in the peritoneal cavity. Of 6 patients with positive cytology at laparoscopy, 4
      had no free cancer cells at operation. The MST was 405 days and one-year survival
      rate was 55.6%. Toxicities were generally mild, and no serious adverse reactions
      were observed. There were only 2 cases of grade 3 neutropenia. In conclusion,
      combination of PTX+FP for NAC appears to be an effective treatment for patients
      with advanced gastric cancer with pyloric stenosis.

PMID- 18079623
TI  - Bi-weekly irinotecan hydrochloride and cisplatin as a second-line chemotherapy
      for patients with advanced gastric cancer.
AB  - PURPOSE: To evaluate the effectiveness of bi-weekly administered irinotecan (CPT
      11) and Cisplatin (CDDP) as a second-line chemotherapy for patients with advanced
      gastric cancer. METHODS: We included 22 patients who were resistant to 5
      fluorouracil (5-FU) -based chemotherapy. CPT-11 (80 mg/m (2)) and CDDP (25
      mg/m(2)) were administered bi-weekly on days 1 and 15 of a 4-week-cycle, on an
      outpatient basis except for the first time. Outcome variables include tumor
      response, toxicity, and survival. RESULTS: Among all patients, 8 responded to the
      therapy, yielding an overall response rate of 36.4% (complete response, n=1;
      partial response, n=7), while 14 did not respond (stable disease, n=9;
      progressive disease, n=5). The time to progression was 5.3 months, and the median
      survival was 10.6 months. Adverse reactions included Grade 3 or 4 leucopenia
      (n=4; 18.2%), Grade 3 or 4 thrombocytopenia (n=1; 4.5%) but all of these patients
      recovered soon (within one week). CONCLUSION: Bi-weekly CPT-11 and CDDP treatment
      was effective and should be considered as a second-line chemotherapy for patients
      with advanced gastric cancer who are resistant to 5-FU based chemotherapy.

PMID- 18079624
TI  - [Clinical study of irinotecan plus infusional fluorouracil/l-leucovorin (FOLFIRI)
      in patients with fluoropyrimidine-resistant metastatic colorectal cancer].
AB  - The clinical efficacy and safety of irinotecan plus infusional fluorouracil/l
      leucovorin (FOLFIRI) in patients with fluoropyrimidine-resistant metastatic
      colorectal cancer were studied retrospectively. 20 patients were treated with
      FOLFIRI at our hospital between October 2003 and November 2005. The objective
      overall response rate was 28% (5/18; 95% confidence interval, 9.7-54%). The
      disease control rate (CR+PR+SD) was 61%. The most frequent grade 3 to 4 adverse
      event was neutropenia, and it was seen in 50%. Non-hematological toxicities were
      mild. The median survival time was 11 months. The 1-year survival rate was 34%.
      This study showed the activity and safety of FOLFIRI in practice.

PMID- 18079625
TI  - [Conversion ratio between intravenous oxycodone/hydrocotarnine and sustained
      release oral oxycodone in patients with cancer pain].
AB  - The demand for oxycodone increases in the treatment of patients with cancer pain,
      but there is no injection formulation containing oxycodone as a single ingredient
      in Japan. Instead, we have an oxycodone/hydrocotarnine compound product. Long
      ago, hydrocotarnine was added to enhance the analgesic effect of oxycodone.
      However, the mechanism of hydrocotarnine is unclear, and few studies have
      mentioned the conversion ratio between intravenous and oral oxycodone. In the
      present study, in order to define the conversion ratio between them, we
      investigated 18 patients treated by intravenous or oral oxycodone and changed to
      another administration route during their treatment. We surveyed the change in
      pain level and adverse effects before and after changing the administration
      route. The conversion ratio from oral oxycodone to intravenous
      oxycodone/hydrocotarnine was 0.71+/-0.12 (mean+/-S. D.), and no obvious change in
      adverse effect was observed.

PMID- 18079626
TI  - [Risk assessment for outpatients for cancer chemotherapy].
AB  - Outpatient treatment in the cancer chemotherapy center was begun in April 2005 at
      the University of Occupational and Environmental Health Hospital. Drugs were
      prescribed 2,590 times during the past year. Times for intravenous drip for
      various regimens and outpatient chemotherapy desired by patients showed a rough.
      The number of incidents was three (0.12%) and no accidents occurred. There were
      74 consultations with pharmacists about prescriptions (2.6%) and 286 (11.0%) with
      nurses. Both types of consultation decreased and their contents were different.
      The number of consultations about prescriptions by special staff at the cancer
      chemotherapy center was less than at other departments. Therefore, a system
      assuring safe management is critically required for the establishment of a system
      for outpatient cancer chemotherapy treatment.

PMID- 18079627
TI  - [Incident surveillance in outpatients treated with hepatic arterial infusion
      (HAI) chemotherapy with infusion pump].
AB  - PURPOSE: An incident situation of hepatic arterial infusion (HAI) chemotherapy
      was investigated, and the improvement methods were evaluated. METHODS: As a
      result of surveillance, all incidents were observed in patients during five day
      continuous HAI infusion conditions: 1) Reverse-flow hemorrhage occurred at home
      by disconnection of the catheter; and 2) hemorrhage by natural withdrawal of the
      huber needle, were diagnosed. For 1) we further taped the catheter connection
      area by Tegaderm and changed the dressing material from SILKYPORE DRESSING (10 x
      13 cm and 4 x 6.5 cm in absorption part) plus two-person fixation by Fixomull
      stretch to IV3000 (9 x 12 cm non-absorption part) plus three-person fixation by
      Fixomull stretch. Moreover, we changed the needle type (subcutaneous adiposus
      thickness) from 22 G x 3/4 inch to 20 G x 1 inch. RESULTS AND CONCLUSIONS: The
      incidents were not observed in 72 patients treated with HAI after improvement. We
      suggest that prevention of hemorrhage by further taping the catheter connection
      and improved stability of the needle by dressing proved effective. In conclusion,
      HAI incident surveillance may well be an important way to care for outpatients
      treated with HAI chemotherapy, and we thus intend to continue the HAI incident
      surveillance to improve the nursing care.

PMID- 18079628
TI  - [An attitude survey on the medical use of narcotics for cancer pain relief].
AB  - Narcotic medications are the major drug therapy for cancer pain relief. A
      clinical use of fentanyl patches and oxycodone extended-release tablets has
      recently become available, which led to more choices of narcotics to be used
      medically. On the other hand, palliative care systems have not yet been fully
      established by medical institutions. The management of symptoms including pain,
      therefore, actually has to be performed by "care doctors" involved in cancer
      care. We conducted a survey on the medical use of narcotics for 500 people,
      including cancer patients and their family members. The result showed that the
      recognition rate of morphine used for cancer pain relief was 88%, while the
      recognition rate of narcotics for medical use other than morphine available for
      cancer pain relief was 20%. The most acceptable dosage form of narcotics was a
      skin patch, followed by an oral preparation. A response percentage that the
      dosage form of medical narcotics should be selectable by users was 93%.

PMID- 18079629
TI  - [A case of angiosarcoma of pelvis with pulmonary metastases which responded to
      paclitaxel].
AB  - A 60-year-old man was admitted to our hospital complaining of back pain and
      bloody sputum. Chest CT scan showed characteristic multiple small nodules with
      central dense opacity and surrounding faint opacity, suggesting lesions with
      hemorrhage. Bone scintigram and MRI revealed multiple osteolytic lesions in
      pelvis and lumbar spine. Biopsy of the bone lesion established a diagnosis of
      angiosarcoma. Chemotherapy with paclitaxel and palliative radiotherapy for the
      bone were initiated. Pulmonary metastases dramatically diminished after 4 courses
      of paclitaxel treatment. After eight weeks, the tumor recurred. Salvage
      chemotherapy of weekly administration of docetaxel yielded limited effects. The
      patient died of cancer one year after treatment initiation.

PMID- 18079630
TI  - [Primary pulmonary Hodgkin lymphoma--two case reports and a review of the
      literature].
AB  - Primary extranodal involvement of Hodgkin lymphoma (HL) is rare. We report two HL
      patients presenting with exclusive or predominant lung involvement. In both
      cases, the results of transbronchial and/or CT-guided lung needle biopsy were
      indicative of granulomatous disease. Eventually, lymph node biopsy specimens
      revealed HL with nodular sclerosis type and lymphocyte-rich type, respectively.
      There were no specific symptoms, laboratory and imaging findings for pulmonary
      HL. A histological examination was required to confirm the diagnosis. Lung biopsy
      techniques such as transbronchial or percutaneous biopsy may be insufficient to
      allow diagnosis of HL. Pulmonary HL should be included in the differential
      diagnosis of lung involvement, even when the pathological evaluation of
      nonspecific inflammation was made from the biopsied specimens.

PMID- 18079631
TI  - [A case of thoracic esophageal cancer with invasion of the main bronchus in which
      long-term survival with high quality of life was achieved through
      chemoradiotherapy, esophageal bypass and then additional chemotherapy].
AB  - We administered chemoradiotherapy consisting of 5-fluorouracil and cisplatin
      combined with radiation (59.8 Gy) to a patient with locally advanced esophageal
      cancer (T4 (left main bronchus) N2M0, stage IVa). The cancer disappeared
      completely after the chemoradiotherapy. However, because an esophagobronchial
      fistula occurred, an esophageal bypass was performed according to the method of
      Postlethwait. Thereafter, multiple lung metastases appeared, which we treated
      with paclitaxel 120-210 mg/body during a total of 23 chemotherapy treatments over
      more than 2 years. For a lesion that recurred in a cervical paraesophageal lymph
      node, we administered 60 Gy of radiation. With these combined therapies, this
      patient survived 50 months as an outpatient with high quality of life. It is
      difficult to treat patients in whom there is direct invasion of the trachea or
      main bronchus by esophageal cancer, and we cannot generalize about the best
      treatment for these patients. This case, however, highlights how to treat such a
      patient so that he retains a high quality of life.

PMID- 18079632
TI  - [S-1 chemotherapy for cancer of the gastric tube used for esophageal
      reconstruction following surgery for esophageal cancer].
AB  - We used S-1 chemotherapy to treat 5 patients with cancer of the gastric tube used
      for esophageal reconstruction through the posterior mediastinal route following
      surgery for esophageal cancer. The response rate was 40%, the median survival 15
      months, and 3 patients still survive. In those 3 patients, the gastric tube
      cancer was at a resectable stage, but the patients elected to have chemotherapy
      instead. One patient has survived 21 months after responding completely to 2
      cycles of combined chemotherapy with S-1 and cisplatin. Another has survived 15
      months after partially respondingto S-1 chemotherapy. And the third has survived
      46 months after endoscopic treatment, radiation therapy and S-1 chemotherapy. S-1
      chemotherapy thus appears to be an effective treatment for cancer of the gastric
      tube after surgery for esophageal cancer.

PMID- 18079633
TI  - [Two cases of stage IV gastric cancer who underwent total gastrectomy and
      achieved long-term survival by sequential chemotherapy].
AB  - We describe two patients, who suffered from Stage IV gastric poorly
      differentiated adenocarcinoma and underwent palliative total gastrectomy, were
      treated by sequential chemotherapy and achieved long term-survival. The first
      patient was a 55-year-old male with peritoneal dissemination. After total
      gastrectomy, he was treated with methotrexate-5-fluorouracil (MTX/5-FU)
      sequential therapy for 5 months, S-1 single-agent therapy for 4 years and weekly
      paclitaxel (PTX) therapy for 9 months. He is being treated with irinotecan (CPT
      11) therapy as an outpatient now, and has achieved 5 year 8-month survival. The
      second patient was a 60-year-old female. We observed unresectable metastases
      around the pancreas, aorta, and transverse mesocolon. She was treated with S-1
      single-agent therapy for 1 year 10 months, MTX/5-FU sequential therapy for 9
      months. She is now receiving weekly PTX therapy for 3 months as an outpatient and
      has achieved 2 year 11-month survival.

PMID- 18079634
TI  - [Complete histological response in gastric cancer stage IV after neoadjuvant
      chemotherapy including S-1 combined with CDDP--report of a case].
AB  - A 60-year-old man complaining of black stool, body weight loss, and anemia, was
      examined and diagnosed with advanced gastric cancer (M, type 3, por 2, cT3, cN3,
      cH0, cP0, cM0, cStage IV). A poor prognosis was predicted, yet we tried
      neoadjuvant chemotherapy (NAC) expecting downstaging of the tumor. Considering
      the efficacy and safety, we chose S-1+CDDP as the NAC regimen. S-1 (120 mg/day)
      was administered orally for 21 days, followed by CDDP (75 mg/body) div on day 8.
      Distal partial gastrectomy and lymph node dissection (D2) were performed, with
      Billroth I reconstruction. Histological examination of the resected stomach and
      lymph nodes revealed no residual cancer cells, suggesting complete histological
      remission (grade 3) according to the Japanese classification of gastric
      carcinoma.

PMID- 18079635
TI  - [Effect of S-1 in a patient with post-operative recurrence of carcinoma of the
      ampulla of Vater].
AB  - We report a case of recurrent carcinoma of the ampulla of Vater with multiple
      lung and abdominal lymph node metastases that well responded to S-1, an oral
      fluoropyrimidine. A 56-years-old woman underwent a pylorus-preserving
      pancreaticoduodenectomy for carcinoma of the ampulla of Vater in October 2003.
      Multiple lung metastases were detected by chest X-ray as a post operative
      screening a year after surgery. Computed tomography showed multiple abdominal
      lymph node metastases. The patient was treated with S-1 (80 mg/day, day 1-28,
      followed by 2 weeks rest) from November 2003. Anti-tumor efficacy was confirmed
      to be partial response by Response Evaluation Criteria in Solid Tumors (RECIST).
      Leukocytopenia, anemia, and mucositis were observed. Every toxicity was mild to
      moderate, and no other severe toxicities were noted. S-1 might be an effective
      and safe agent for carcinoma of the ampulla of Vater.

PMID- 18079636
TI  - [A patient with recurrent sigmoid colon cancer in whom pleural effusion and
      ascites resolved after FOLFOX 4 therapy].
AB  - We performed combination therapy with oxaliplatin/l-LV/5-FU (FOLFOX 4) in a
      patient with recurrent colorectal cancer (a 58-year-old man) who had pleural
      effusion and ascites. This resulted in disappearance of the pleural effusion and
      ascites, as well as negative tumor markers. Surgery was performed for sigmoid
      colon cancer on September 29, 2004. In February 2006, abdominal swelling was
      observed, and CEA increased to 15 ng/mL with multiple intraabdominal tumor
      nodules. The patient was diagnosed as having peritonitis carcinomatosis
      associated with recurrent sigmoid colon cancer, and was treated with FOLFOX 4.
      CEA was 134.9 ng/mL before treatment, but became negative after six courses,
      while his pleural effusion and ascites disappeared after 10 courses of treatment.
      This treatment also appeared to be useful for recurrent colorectal cancer with
      peritoneal dissemination.

PMID- 18079637
TI  - [Two cases of advanced low rectal cancer, preoperative chemo-radiation therapy
      leading to complete histological response].
AB  - We report two cases of advanced low rectal cancer, with preoperative chemo
      radiation therapy leading to a complete histological response. Case 1 was a 74
      year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo
      radiation (a total of 45 Gy radiation+oral 5'-DFUR 800 mg/day for 3 weeks) was
      performed. Then, 30 days after chemo-radiation, we conducted a low anterior
      resection with lymph node dissection. Histological examination revealed no
      residual cancer cells in the resected specimen. Case 2 was a 35-year-old male who
      was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a
      total of 45 Gy radiation+5-FU 500 mg/day+CDDP 10 mg/day for 3 weeks) was
      performed. 28 days after chemo-radiation, we conducted an abdominoperineal
      resection with lymph node dissection and a partial resection of the liver.
      Histological examination revealed well-differentiated adenocarcinoma in the
      resected liver tissue, but a rectal tumor was replaced by scar tissue with no
      viable cells.

PMID- 18079638
TI  - [A case report--combination chemotherapy with oral UFT and CPT-11, 5-FU, l-LV by
      hepatic arterial infusion for multiple hepatic metastasis from sigmoid colon
      cancer].
AB  - A 64-year-old woman was diagnosed with multiple hepatic metastases from sigmoid
      colon cancer. She underwent resection of the colon and catheter insertion into
      the hepatic artery for arterial infusion in August 2006. She was then treated
      with postoperative combination chemotherapy consisting of UFT and CPT-11, 5-FU, l
      LV. UFT was administered orally at 400 mg/body/day every day and CPT-11 was
      injected at 100 mg/body/week, 5-FU at 750 mg/body/week, and l-LV at 300
      mg/body/week for 8 continuous weeks. After 2 months of the chemotherapy, the
      metastatic liver tumors disappeared. So hepatic arterial infusion with the same
      regimens was injected once every month 4 more times. Oral UFT was administered
      every day. After 6 months of the combined chemotherapy above, we judged the
      effects of the chemotherapy to be a complete response. Then the chemotherapy was
      followed by oral UFT only. As severe nausea and vomiting were seen in this
      patient with an initial dose of 150 mg/body/week of CPT-11 at first, we reduced
      the dose of CPT-11 to 100 mg/body/week. From then, outpatient care was possible
      because no severe events were observed. Combined chemotherapy consisting of oral
      UFT and CPT-11, 5-FU and l-LV by hepatic arterial infusion is suggested to be a
      new and effective treatment for multiple liver metastases from colorectal cancer.

PMID- 18079639
TI  - [A case of metastatic rectal cancer from serous adenocarcinoma of the ovary].
AB  - A 51-year-old woman was hospitalized with constipation and bloody feces. Under
      diagnosis of a primary rectal cancer with peritonitis, an ileostomy was
      scheduled. Since peritoneal dissemination was found, histologically she was
      diagnosed as metastatic rectal cancer from serous adenocarcinoma of the ovary.
      Chemotherapy with paclitaxel and carboplatin was performed, and complete
      disappearance on assessable examination was seen. Eight months after the first
      operation, she underwent total hysterectomy, oophorectomy and low anterior
      resection of rectum. No viable cancer tissue could be found. After the second
      operation, she has been doing well without any recurrence for 1 year and half.

PMID- 18079640
TI  - [A case undergoing repeated anaphylactic shock after systemic administration of
      vinorelbine].
AB  - We here describe a 49-year-old man who suffered repeated anaphylactic shock after
      systemic chemotherapy with vinorelbine for stage IV left lung adenocarcinoma
      (S1+2). He was treated using a combination of cisplatin and weekly irinotecan
      (CPT-11) as the first line; however, the regimen was changed to a combination of
      vinorelbine (VNR) and gemcitabine (GEM) because of his progressive disease. He
      was admitted to our hospital for examination of the unknown cause of hypotension
      and loss of consciousness. The second shock occurred after eating pistachios, and
      the third one at cancerous pain. After pain control, the shock no longer
      occurred. Anaphylactic shock may show two peaks and late symptoms. In patients
      with a history of anaphylactic shock, we should pay attention to foods, drugs,
      and various stresses which might cause anaphylaxis.

PMID- 18079641
TI  - [Contradictions in Japanese classification of gastric carcinoma (JCGC) and a
      proposal for revision].
AB  - In today's rapid advancement in gastric cancer research, the role played by the
      JCGC is considerable. On the other hand, there are fundamental contradictions,
      and they will definitely present problems for research in the future. In this
      paper, these points were clarified, and a proposal for their revision was made.
      The contradictions are as follows: 1) lymph node grading based on the removal
      effect; 2) variable and inconsecutive grading according to the location of the
      primary lesion; 3) lymph node grading that assumes distal gastrectomy in lower or
      middle part of cancer; and 4) changing not only the location category but also
      the station to be dissected at each revision. To assure that the rule book will
      be accepted by many medical practitioners, it is important to clearly separate it
      from the role of a clinical guideline. This writer proposes that the JCGC
      classification must be revised in conformity with the TNM classification for a
      global standard and there must be cooperation in improving the clinical guideline
      regarding rules such as those for lymph node dissection.

PMID- 18079642
TI  - From the editor.

PMID- 18079643
TI  - OSCAR gans on paul gerson unna*.

PMID- 18079644
TI  - Eosinophilic globules in Spitz's nevi: New findings and a diagnostic sign.
AB  - Dull pink globules were found within the epidermis in 65% of junctional, 75% of
      compound, and 25% of intradermal types of Spitz's nevi (the nevi of large spindle
      and/or epithelioid cells). These globules were PAS-positive, diastase-resistant
      and also were positive with the trichrome stain. Similar-appearing eosinophilic
      globules were noted in the epidermis in only 2% of malignant melanomas and in but
      0.9% of ordinary melanocyte nevi. The globules in malignant melanomas and in
      ordinary melanocytic nevi were negative with PAS and trichrome stains. Therefore,
      the finding of PAS- and tri-chrome-positive eosinophilic globules within the
      epidermis is a helpful sign for histologic differentiation of Spitz's nevus from
      malignant melanoma.The histologic differentiation of Spitz's nevus (the nevus of
      large spindle and/or epithelioid cells) from malignant melanoma is of utmost
      importance in dermatopathology. Most authors agree that no single histologic
      finding enables absolute differentiation of the benign neoplasm from the
      malignant one. One of us (HK), while reviewing a large series of melanocytic
      lesions, observed distinctive eosinophilic globules within the epidermis and the
      dermis of many specimens of Spitz's nevus. The microscopic appearance of these
      globules and their significance is the subject of this paper.

PMID- 18079645
TI  - Fibrous papule of the face.

PMID- 18079646
TI  - Preservation of Scleral Grafts to Avoid HIV Infection.

PMID- 18079647
TI  - Anterior lamellar sclerectomy for nanophthalmos.
AB  - A 38-year-old woman with nanophthalmos suffered bilateral acute angle closure
      glaucoma. Peripheral iridotomies were unsuccessful in maintaining low intraocular
      pressure in either eye. The left eye had probable ciliary block glaucoma and was
      treated with subsequent pars plana vitrectomy and trabeculectomy. Further
      postoperative complications included a serous choroidal detachment treated by a
      lamellar sclerectomy in three quadrants with sclerotomies and drainage of
      suprachoroidal fluid. These procedures were successful in achieving a well-formed
      left globe with normal intraocular pressures. The right eye, however, continued
      to manifest elevated intraocular pressure despite peripheral iridoplasties.
      Before further intraocular surgery in the right eye, prophylactic lamellar
      sclerectomies in each quadrant, as well as sclerotomies in the inferior two
      quadrants, were performed in the hope that preplacement might reduce
      postoperative sequelae of anticipated filtering surgery and/ or vitrectomy.
      Surprisingly, the lamellar sclerectomies alone resulted in excellent intraocular
      pressure control. The pathogenesis of nanophthalmos is discussed in view of this
      finding.

PMID- 18079648
TI  - Molteno implants in children.
AB  - We report our experience with Molteno implants in 27 eyes of 20 children with
      glaucoma. Associated ocular findings included Sturge Weber syndrome (one
      patient), aniridia and retinoschisis (one patient), aphakia (seven patients,
      eight eyes), rubella syndrome (two patients), Peters anomaly (one patient), and
      Treacher Collins syndrome (one patient). Fifteen eyes received a single-plate
      implant, and 12 eyes received a double-plate implant in two stages. The patients'
      ages ranged from 2 months to 13 years (mean 47 +/- 55 months). The average number
      of previous glaucoma procedures was four per eye (range two to 10). The follow-up
      period ranged from 6 to 36 months (mean 20 +/- 9 months). The mean intraocular
      pressure before surgery was 34 +/- 4 mm Hg. The mean postoperative intraocular
      pressure was 19 +/- 11 mm Hg at 1 month and 19 +/- 6 mm Hg at 1 year (p < 0.001
      at both times). After surgery nine eyes (33.3%) required no medication for
      control of intraocular pressure. Additional surgery was required in 12 eyes
      (44.4%). We believe the Molteno implant is a useful approach for children with
      glaucoma who fail to respond to standard medical and surgical treatments.

PMID- 18079649
TI  - Hypotensive effect of pilocarpine after argon laser trabeculoplasty.
AB  - The exact mechanism of action of argon laser trabeculoplasty (ALT) has only been
      presumptively proposed. There are two hypotheses of action of ALT: the first is
      the mechanical theory and the second is centered on the possibility of laser
      induced modifications of trabecular cells. The goal of our investigation was to
      verify if pilocarpine determines a decrease of intraocular pressure mainly by a
      mechanical stretching of the meshwork; if pilocarpine could lower intraocular
      pressure after ALT; and thus if the mechanism of action of laser treatment could
      mainly be attributable to a mechanical strain of the trabecular meshwork. Twenty
      one patients affected with primary open angle glaucoma had been recruited for the
      study. Twenty-one eyes underwent trabeculoplasty. All the patients were followed
      for 6 months. Statistical analysis of the data revealed that pilocarpine was not
      able to induce a further decrease of intraocular pressure after trabeculoplasty.
      Moreover, the maximum decrease of intraocular pressure induced by pilocarpine
      before laser treatment was not statistically different from the tensional values
      after ALT. The results of the present investigation suggest that the mechanism of
      action of trabeculoplasty is probably attributable to a mechanical stretching of
      the trabecular meshwork and the results show the inefficacy of pilocarpine after
      laser treatment in the management of glaucomatous patients.

PMID- 18079650
TI  - A comparison of the ocular hypotensive efficacy of twice-daily 0.25% levobunolol
      to 0.5% timolol in patients previously treated with 0.5% timolol.
AB  - Treatment with noncardioselective beta-adrenoceptor antagonists (e.g., 0.5%
      timolol or 0.5% levobunolol) is standard practice for lowering elevated
      intraocular pressure (IOP). However, because there are risks and side effects
      associated with the use of these agents, a lower, yet still effective, dose may
      be preferred. We gave 0.5% timolol twice daily for 30 days to 143 patients. In a
      double-masked, randomized fashion, we then assigned patients to continue to
      receive 0.5% timolol twice daily or 0.25% levobunolol twice daily for 8 weeks.
      The mean unmedicated baseline IOP for both groups was approximately 25 mm Hg.
      After 30 days of timolol pretreatment, the mean IOP in both groups decreased to
      approximately 19 mm Hg (p = 0.210). After the 30-day timolol pretreatment period,
      and subsequent randomization to either 0.5% timolol or 0.25% levobunolol
      treatment, there was little change in overall mean IOP (0.03 mm Hg decrease for
      levobunolol, 0.06 mm Hg increase for timolol; p = 0.811) from the timolol
      pretreatment baseline. One patient assigned to the timolol treatment group was
      terminated from the study due to inadequate control of IOP. We conclude that the
      mean IOP lowering effect of 0.25% levobunolol is equivalent to 0.5% timolol, and
      switching patients from twice-daily 0.5% timolol to twice-daily 0.25% levobunolol
      poses no significant risk of decreased ocular hypotensive efficacy.

PMID- 18079651
TI  - Argon laser peripheral iridoplasty for angle-closure glaucoma in sibilings with
      weill-marchesani syndrome.
AB  - A patient with Weill-Marchesani syndrome and angle-closure glaucoma had
      persistent appositional closure after laser iridotomy that was unrelieved by
      topical application of either miotic or cycloplegic agents. Argon laser
      peripheral iridoplasty successfully opened the angle. The patient's sister also
      had Weill-Marchesani syndrome and angle closure unrelieved by laser iridotomy.
      Angle closure in Weill-Marchesani syndrome and the response to laser iridotomy
      and treatment with either miotic or cycloplegic agents may be complex and depends
      on the relative proportion of pupillary block as a mechanism underlying the angle
      closure, the functional status of the zonular apparatus, and the degree of angle
      crowding by the peripheral iris in the presence or absence of peripheral anterior
      synechiae.

PMID- 18079652
TI  - Hemorrhage of the optic disc and neurosensorial dysacousia.
AB  - Forty-one high-tension glaucoma patients. 16 normotensive glaucoma patients, and
      30 normals were studied in relationship to neurosensorial dysacousia. Although
      frequency of dysacousia was higher in normotensive glaucoma (87.5%) in comparison
      with high-tension glaucoma (75.69%) and normals (76.6%). this was not
      statistically significant (p = 0.53). When we compared glaucoma patients with and
      without hemorrhages of disc. 100% of the former had neurosensorial dysacousia and
      71.4% of the latter had it (p = 0.047). The association of vascular disease in
      neurosensorial dysacousia and its association with hemorrhages of the optic disc
      suggest that there could be a common vascular denominator in both diseases.

PMID- 18079654
TI  - Acute angle-closure glaucoma secondary to chlor-trimeton.

PMID- 18079653
TI  - Reproducibility of quantitative anterior chamber angle measurements with
      scheimpflug video imaging.
AB  - A Scheimpflug video camera with digital image analysis was used to assess
      iridocorneal angles in 11 eyes with nonoccludable open angles and nine eyes with
      occludable narrow angles. Normal eyes had a mean angle width of 28.2 +/- 2.5
      degrees and eyes with occludable narrow angles had a mean angle width of 17.5 +/-
      3.2 degrees . Interobserver variability was 1.98 degrees and 1.94 degrees in open
      and narrow angles, respectively. Intraobserver variability was 1.81 degrees .
      This technique provides a method for longitudinal observation and quantitative
      assessment of the iridocorneal angle.

PMID- 18079655
TI  - Variability of intraocular pressure after auditory stimulation in rabbits.

PMID- 18079656
TI  - Combined cataract extraction and trabeculectomy: surgical techniques.

PMID- 18079657
TI  - Pattern electroretinogram: an electrophysiological technique applicable to
      primary open-angle glaucoma and ocular hypertension.

PMID- 18079658
TI  - Is there an indication for full-thickness filtration surgery?

PMID- 18079659
TI  - The effects of preferred practice patterns on physician malpractice concerns in
      glaucoma.

PMID- 18079660
TI  - Prelude to an outcome.

PMID- 18079661
TI  - Removable sutures in the titration of trabeculectomy beld function.

PMID- 18079662
TI  - Reply.

PMID- 18079664
TI  - Glaucoma highlights.

PMID- 18079663
TI  - Early postoperative titration of bleb function: argon laser suture lysis and
      removable sutures in trabeculectomy.

PMID- 18079667
TI  - [Introduction. Pharmacogenetics].

PMID- 18079668
TI  - [Pharmacogenetics: from basic research to clinical applications].
AB  - Pharmacogenetics is the study of the genetic factors implicated in the
      pharmacological or toxicological response to drugs. This response is very
      variable and depends on three steps: metabolism/transport, target and organism
      reaction. Each step is very variable as a function of endogenous (patho
      physiological, genetics...) or exogenous (environment: drugs, diet, smoking,
      alcohol...) factors. The scientific bases of pharmacogenetics have been strongly
      established: genetic polymorphisms have an impact on pharmacological activity or
      on the toxicity of numerous drugs and examples are given in this review. By
      contrast, present clinical applications are more limited although, in some
      instances, medical and economic interest of the pre-treatment determination of
      genotype or phenotype of the patients has been clearly demonstrated. Certain
      hospital laboratories now include pharmacogenetic activity. The predictive or
      explicative value of pharmacogenetics is scientifically demonstrated but
      prospective studies for validation are now necessary to identify situations where
      a clinical application will be actually beneficial for patients.

PMID- 18079669
TI  - [Molecular pharmacogenetics in hospital laboratories in France: current data and
      future prospects].
AB  - Molecular pharmacogenetic units have recently been established in several
      hospital laboratories in France. The clinical impact of these units is still
      limited and numerous problems of organizational, ethical, legal, technical,
      social and economical nature remain to be resolved. However, an increasing number
      of these units, a rise in their activities and an enlargement of their scope of
      application are foreseeable in the future. Ultimately, these units would
      significantly contribute to limit the public health problem caused by
      interindividual variabilities in drug effects. In view of these prospects, it
      seems essential that such hospital activity should be quickly recognised by the
      authorities and the various health sectors in France. It is also essential that
      the problems that arise from such pharmacogenetic activities should be considered
      by the authorities and would profit from the organization of a national network
      and from financial guarantees.

PMID- 18079670
TI  - [Pharmacogenetics and immunosuppressor drugs: impact and clinical interest in
      transplantation].
AB  - The domain of solid organ transplantation is characterized by the use of variable
      drug combinations with drug-drug interactions, and the presence of two genomes,
      that of the transplanted organ and that of the receiver, which can be involved in
      the pharmacogenetics of these drugs. This paper is a literature review of the
      impact of the genetic polymorphisms of the metabolic enzymes, efflux transporters
      and therapeutic targets of the main immunosuppressive drugs (cyclosporine,
      tacrolimus, sirolimus and mycophenolate) on the dose-concentration and
      concentration-effect relationships of these drugs. The polymorphisms of metabolic
      enzymes have significant effects on the pharmacokinetics of all these drugs, but
      the clinical trials for validating treatment individualization based on these
      genetic differences are still lacking. It should be noted that the influence of
      the donor's genome has seldom been studied and has been found to be significant
      in liver transplant recipients. The influence of efflux transporter genes
      polymorphisms, in particular of P-glycoprotein and MPR2, is controversial. As for
      the polymorphisms of the drug targets genes, either they have not been reported
      (calcineurin, mTOR), or their influence has only been the subject of a few
      preliminary studies (IMPDH2). The pharmacogenetics of immunosuppressants is thus
      still an open field for investigations and potential therapeutic progress.

PMID- 18079671
TI  - [Pharmacogenetics of anti-cancer drugs].
AB  - Toxic side-effects of cytotoxic drugs is a stumbling-block of chemotherapy due to
      the fact that their therapeutic index is narrow. New approaches are necessary to
      individualize the treatments. Pharmacogenetic analysis is facilitated by easy
      access to the patient genome via simple blood samples, by the large number of
      known genes of interest coding for drugs targets or metabolism enzymes and by the
      fact that their polymorphism (SNP) is often known. Presently more focused on the
      prevention of toxic side-effects, pharmacogenetics already provides a good deal
      of confirmed data for clinical applications, such as the detection of
      dihydropyrimidine dehydrogenase deficiency by sequencing, or UGT1A1 7/7 genotype
      detection in Gilbert's syndrome for the prevention of 5-FU and irinotecan-induced
      severe toxicities. It must be emphasized that a SNP which is deleterious for
      enzyme activity is rarely a contraindication for the drug, provided that some
      precautions are taken and appropriate therapeutic advice is given by experts.

PMID- 18079672
TI  - [Conclusion].

PMID- 18079673
TI  - [Notion of threshold in mutagenesis: implications for mutagenic and carcinogenic
      risk assessment].
AB  - During years, it has been widely admitted in the scientific community that there
      was no threshold in mutagenesis: a compound was or not a mutagen. The meaning of
      such a proposition was that a risk existed at all exposure level, because, at
      least theoretically, one molecule is sufficient to cause the formation of a DNA
      adduct which is able to induce a mutation. However, works carried out in the last
      few years have shown that in the case of some specific mechanisms of mutagenesis,
      a threshold could be demonstrated essentially in the case of compounds that do
      not react directly with DNA. Several types of thresholds exist, and the simple
      statistical threshold is not sufficient in terms of risk assessment. A biological
      threshold that is consistent with a mechanism of action of the mutagen should be
      established. Amongst these mechanisms, we can mention some mechanism with a
      demonstrated threshold: effects of aneugens, effects of topoisomerases
      inhibitors, effects of DNA polymerases inhibitors, effects of compounds with a
      different metabolism at high doses compared to low doses. On the contrary, for
      some mechanisms, the demonstration of the mechanism is suspected, but not totally
      demonstrated. It is the case of compounds which induce nucleotides pool imbalance
      or compounds which are DNA repair inhibitors. In some cases, when a redundancy
      exists in the repair of damages, like oxidative DNA damage, a threshold is
      suspected. Some authors even recently proposed the possibility of a threshold in
      the case of alkylating agents. The majority of mutagenic thresholds were
      demonstrated in vitro, however some mechanisms were demonstrated in vivo, for
      example in the case of micronucleus induction by hypo or hyperthermia in rodents
      bone marrow. The use of threshold in risk assessment requires the use of the most
      sensitive endpoint for example, non disjunction in the case of aneugens,
      confusing factors like apoptosis should be eliminated and species sensitivities
      should be taken into account. A very important point to consider is to
      demonstrate that the mechanism with threshold was really thee only one involved
      in the mutagenic effect. The demonstration of such thresholds is of particular
      interest for human risk assessment in the case of mutagens and of genotoxic
      carcinogens.

PMID- 18079674
TI  - [Overview on neurogenesis induced by organophosphate poisoning: results and
      perspectives].
AB  - Nerve agents could be potentially used as during a conflict or a terrorist
      attack. If an emergency treatment is not provided after poisoning, irreversible
      brain damages and behavioural sequels are expected to appear. In vivo cell
      therapy seems to be a promising approach for delayed treatment to contribute to
      brain repair. A mobilization of endogenous neural progenitors would be the basis
      of such an approach. After migrating, these progenitors would engraft in damaged
      brain regions and subsequently differentiate into functional neurons. In this
      review, after a few reminders regarding nerve agent poisoning and the emergency
      treatment of such an intoxication, progresses in terms of cell therapy and its
      potential application to nerve agent-induced brain lesions are summarized.

PMID- 18079675
TI  - Purification of the full-length Xenopus interphotoreceptor retinoid binding
      protein and growth of diffraction-quality crystals.
AB  - PURPOSE: Interphotoreceptor retinol-binding protein (IRBP), composed of two or
      four homologous modules in tandem, plays an important role in retinoid
      trafficking between the retinal pigmented epithelium, photoreceptors, and Muller
      cells. The exact nature of this role is not yet clear. Attempts to purify the
      full-length retinal IRBP to homogeneity for crystallization purposes have largely
      been unsuccessful, owing primarily to instability and denaturation of the protein
      at high concentrations in aqueous media. METHODS: A bacterial expression system
      was used for the production of the recombinant full-length four modules
      containing Xenopus IRBP (xIRBP; 1197 amino acids; 131 kDa). An optimized
      purification strategy and the presence of molar excesses of a thiol-based
      reducing agent yielded highly pure xIRBP in a soluble, stable and active form,
      free of its fusion partner. Binding of all-trans retinol was characterized by
      fluorescence spectroscopy monitoring ligand-fluorescence enhancement, quenching
      of endogenous protein fluorescence, and energy transfer. RESULTS: We grew the
      first diffraction-quality crystal of xIRBP. We have gathered diffraction data
      from these crystals to 2.46 A resolution, sufficient to yield an atomic model of
      the tertiary structure of IRBP. Retinol-binding results determined by
      fluorescence spectroscopy show roughly one retinol-binding site per polypeptide
      chain. CONCLUSIONS: The binding stoichiometry taken together with modeling data
      suggest that not all modules are functionally equivalent. Determination of the
      full-length IRBP structure will be a significant breakthrough in understanding
      the functional roles of IRBP in the visual cycle. The advances presented here
      will not only lead to the structure of the full-length IRBP, but will allow us to
      understand how the modules interact in the function of IRBP. Furthermore, these
      studies will allow characterization of the ligand-binding site(s) with bound
      ligand(s).

PMID- 18079676
TI  - A recurrent FBN1 mutation in an autosomal dominant ectopia lentis family of
      Indian origin.
AB  - PURPOSE: To identify the genetic defect in an autosomal dominant ectopia lentis
      (EL) family having 27 affected members in four generations. METHODS: Detailed
      family history and clinical data were recorded for 48 family members including 24
      persons with isolated ectopia lentis. Candidate gene regions at 5q and 15q known
      to be linked with ectopia lentis were analyzed using fluorescent labeled
      microsatellite markers. Mutation screening in the candidate gene, fibrillin-1
      (FBN1), at 15q was performed by bidirectional sequencing of the amplified
      products. RESULTS: A maximum LOD score of 5.74 at theta=0.0 was obtained with
      marker D15S1024 in close proximity to FBN1 at 15q21. Mutation screening in FBN1
      identified a C>T transition at nucleotide position c.718. This nucleotide change
      resulted in the substitution of highly conserved arginine by cysteine at codon
      240 (R240C). This nucleotide substitution was not seen in any unaffected member
      of the family. CONCLUSIONS: We report a recurrent R240C mutation in FBN1 in an
      autosomal dominant ectopia lentis family. This mutation has previously been
      reported in a family with isolated ectopia lentis, in another family with ectopia
      lentis and involvement of the skeleton and integument, and in one person with
      classic Marfan syndrome. This is the largest family with isolated ectopia lentis
      reported to date. The results of the present study provide convincing evidence
      for a correlation of R240C and isolated ectopia lentis. In addition, this is the
      first report of molecular characterization in an ectopia lentis family of Indian
      origin.

PMID- 18079677
TI  - Functional involvement of scavenger receptor class B, type I, in the uptake of
      alpha-tocopherol using cultured rat retinal capillary endothelial cells.
AB  - PURPOSE: Alpha-Tocopherol is an essential micronutrient acting as an antioxidant
      in the retina. However, the molecular mechanism of its retinal uptake from the
      circulating blood remains to be determined. The purpose of this study was to
      elucidate the contribution of scavenger receptor class B, type I (SR-BI), to the
      uptake of high-density lipoprotein (HDL)-associated alpha-tocopherol (alpha
      tocopherol-HDL) using a conditionally immortalized rat retinal capillary
      endothelial cell line (TR-iBRB2 cells), as an in vitro inner blood-retinal
      barrier model. METHODS: An uptake study of alpha-tocopherol-HDL was performed
      using TR-iBRB2 cells. The expression of SR-BI protein was determined by
      immunoblot and immunohistochemical analyses. RNA interference was done to clarify
      the relationship between SR-BI protein expression and the uptake of alpha
      tocopherol-HDL by TR-iBRB2 cells. RESULTS: [(14)C]alpha-tocopherol-HDL uptake by
      TR-iBRB2 cells exhibited a time-dependent increase and a temperature-dependence
      with an 88% reduction for 90 min at 4 degrees C compared with that at 37 degrees
      C. The uptake of [(14)C]alpha-tocopherol-HDL was inhibited by BLT-1, a specific
      inhibitor of the SR-BI-mediated lipid transfer between HDL and cells, in a
      concentration-dependent manner with an IC(50) of 23.2 nM. SR-BI protein
      expression was detected in TR-iBRB2 cells and SR-BI immunostaining was observed
      along the rat retinal capillaries. Inhibition of SR-BI protein expression by SR
      BI siRNA resulted in a 24.4% reduction in [(14)C]alpha-tocopherol-HDL uptake.
      CONCLUSIONS: Our findings strongly suggest that SR-BI at the inner blood-retinal
      barrier is responsible for alpha-tocopherol uptake from the circulating blood and
      plays a key role in maintaining alpha-tocopherol in the neural retina.

PMID- 18079678
TI  - A possible mechanism of microglia-photoreceptor crosstalk.
AB  - PURPOSE: The goal of this study was to explore the relationship between
      photoreceptor apoptosis and retinal microglial activation. METHODS: A murine
      photoreceptor cell line (661W cells) was exposed to LPS-treated microglial cell
      conditioned medium (MGCM), and cell viability was assessed by terminal dUTP
      transferase nick end labeling (TUNEL) and the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. In addition, microglia were exposed to
      culture media from light-damaged 661W photoreceptor cells (PRCM), and microglial
      activation was assessed morphologically by phase contrast microscopy. Reverse
      transcription polymerase chain reaction was used to examine mRNA levels of
      several chemokines and noxious factors in the MGCM-treated photoreceptor cells
      and the PRCM-treated microgial. Western blotting was used to analyze NF-kappaB
      p65 subunit, phosphorylated MAPKs p38, p44/42 (Erk1/2), and c-Jun N-terminal
      kinase (JNK). RESULTS: Our results showed 37% of 661W cells underwent apoptosis
      following exposure to MGCM for 24 h. MGCM-induced death was associated with down
      regulation of chemokine expression (i.e., eotaxin and RANTES), upregulation of
      inflammatory mediators (i.e., MIP-1alpha, MIP-1beta, IL-10, iNOS, and TNF-alpha),
      and increased phosphorylation of p38, p44/p42, and JNK. Retinal microglia
      acquired an activated phenotype after exposure to PRCM for 24 h. Microglial
      activation was accompanied by increased NF-kappaB p65 expression, increased
      phosphorylation of p38 and JNK, and upregulation of chemokines (i.e., eotaxin and
      RANTES) and inflammatory mediators (i.e., iNOS and IL-10). CONCLUSIONS: Light
      damaged photoreceptors release immunological signaling molecules that attract
      microglia, resulting in microglial activation and subsequent further degeneration
      of remaining photoreceptors. These results also suggest that p38, p44/42, and JNK
      may regulate glial-induced photoreceptor death and that p38, JNK, and NF-kappaB
      may regulate photoreceptor-induced microglial activation.

PMID- 18079679
TI  - Proteomic profiling of human retinal and choroidal endothelial cells reveals
      molecular heterogeneity related to tissue of origin.
AB  - PURPOSE: The ocular vascular endothelium plays a key role in the development of
      several leading retinal causes of blindness in Western nations. Choroidal
      endothelial cells are integral to the subretinal neovascular lesions that
      characterize the exudative form of late age-related macular degeneration (AMD),
      and retinal endothelial cells participate in the initiation of diabetic
      retinopathy and posterior uveitis. Vascular endothelial cells at different sites
      exhibit considerable molecular diversity. This diversity has implications for
      understanding the pathogenesis of tissue-specific diseases and for the
      development of targeted therapies to treat these conditions. Previous work from
      our group has identified significant differences in the gene transcript profiles
      of human retinal and choroidal endothelial cells. Because the proteome ultimately
      determines the behavior of any given cell, however, it is critical to determine
      whether molecular differences exist at the level of protein expression. METHODS:
      Retinal and choroidal endothelial cells were separately isolated from five sets
      of human eyes by enzymatic digestion with type II collagenase followed by anti
      CD31 antibody-conjugated magnetic bead separation. Cells were washed to remove
      serum peptides in the culture medium, and lysed by sonication in buffer
      containing 2% sodium dodecyl sulfate. Protein was then precipitated with acetone.
      Retinal and choroidal endothelial samples from each donor were labeled with Cy3
      and Cy5, respectively, mixed with a Cy2-labeled pooled protein sample to
      facilitate spot matching across gels, and separated by two-dimensional difference
      gel electrophoresis (2D-DIGE). Following a global normalization, differentially
      abundant protein spots that were visible in at least four of five donor gels were
      detected by the significance analysis of microarrays method, with false discovery
      rate set at 5%. Corresponding spots were excised from additional DIGE-labeled or
      Coomassie-stained 2D electrophoretic gels. Protein identification was performed
      by liquid chromatography and tandem mass spectrometry. RESULTS: Of 123 protein
      spots detected by 2D-DIGE that qualified for statistical analysis, we found 31
      spots that demonstrated a significant difference in abundance between retinal
      endothelial samples versus choroidal endothelial samples. For 17 proteins, over
      50% of the spectral counts could be matched to a single protein in the digested
      spot. Eleven proteins were more abundant in retinal endothelial cells (i.e.,
      inorganic pyrophosphatase, protein disulfide isomerase A3, calreticulin,
      peroxiredoxin-4, protein disulfide isomerase, serpin B9, F-actin capping protein
      subunit beta, coactosin-like protein, vimentin, cathepsin B, and a high molecular
      weight form of annexin A3). Six proteins were more abundant in choroidal
      endothelial cells (i.e., glutathione peroxidase 1, ubiquitin carboxyl-terminal
      hydrolase isozyme L1 (UCH-L1), heat-shock protein beta-1, superoxide dismutase
      (Cu-Zn), nucleoside diphosphate kinase A, and a low molecular weight form of
      annexin 3). CONCLUSIONS: Our data indicate that the proteomes of retinal and
      choroidal vascular endothelial cells are different. Several differentially
      expressed proteins are implicated in the regulation of angiogenesis; these
      include cathepsin B and UCH-L1, proteins with transcripts that were also
      differently expressed according to microarray. Our observations further suggest
      that angiogenesis within the retina, a component of severe diabetic retinopathy
      and posterior uveitis, may be controlled by different mechanisms to those
      regulating choroidal neovascularization, as occur in exudative AMD. Future
      studies to establish the role of these angiogenic proteins in disease may suggest
      potential new targets for tissue-specific therapies.

PMID- 18079680
TI  - Expression of melanin-related genes in cultured adult human retinal pigment
      epithelium and uveal melanoma cells.
AB  - PURPOSE: Controversy exists over melanogenesis of adult human RPE cells in vitro.
      This study investigated melanin content and production and expression of
      tyrosinase (TYR), tyrosinase-related-protein-1 (TRP1), tyrosinase-related-protein
      2 (TRP2), and P gene in cultured human RPE cells and uveal melanoma cells.
      METHODS: RPE cells were isolated and cultured from three adult donor eyes. A
      continuous human uveal melanoma cell line was established from primary choroidal
      melanoma. Melanin content and production were measured, and the expression of
      TYR, TRP1, TRP2, and P gene at the mRNA and protein levels were detected by RT
      PCR and western blot, respectively. RESULTS: Melanin content per cell of cultured
      RPE decreased rapidly and in proportion to cell division. No melanin production
      could be demonstrated in any passages. In cultured RPE cells, mRNA expression of
      TYR, TRP1, TRP2, and P-gene and protein expression of TYR, TRP1, and TRP2 could
      not be detected. In uveal melanoma cells, melanin content per cell remained
      stable, and melanin production could be detected in each passage. Expression of
      mRNA of TYR, TRP1, TRP2, and P-gene and protein of TYR, TRP1, and TRP2 could be
      detected in melanoma cells. CONCLUSIONS: Human RPE cells under standard culture
      circumstances do not produce melanin and do not express the four key genes
      required in melanin biosynthesis pathway. In contrast, human uveal melanoma cells
      produce melanin and express all of these melanogenic genes in vitro.

PMID- 18079681
TI  - Demonstration and use of nanoliter sampling of in vivo rat vitreous and
      vitreoretinal interface.
AB  - PURPOSE: An understanding of the chemical microenvironments at different
      locations on the retina can provide unique insights into retinal neurochemistry
      and pathology. The anatomical shape and the small volumes available from a
      spatially restricted volume greatly complicate these types of measurements. The
      aim of this study was to demonstrate an in vivo sampling system to probe
      different regions of the rat retina. METHODS: A low-flow push-pull perfusion
      probe was developed with concentric fused-silica capillaries. It was designed to
      fit through a 29-gauge needle for placement in the vitreous and at the
      vitreoretinal interface of the rat eye. Physiological saline was perfused and
      withdrawn through outer and inner capillaries, respectively, at flow rates
      between 10 and 50 nl/min. Samples of 500 nl were collected for amino acid
      analysis by capillary electrophoresis. Perfusion of a potent and selective
      inhibitor of the excitatory amino acid transporters was performed through the
      probe with the tip located 1-2 mm away from the optic nerve head. RESULTS: Ten
      amino acids were quantified from the perfusates of vitreous and the vitreoretinal
      interface. Sampling through time showed the use of this system to monitor retinal
      changes in these amino acids. The infusion of a transport protein antagonist
      shows a statistically significant increase in the glutamate concentration in
      collected samples when the probe tip is placed peripheral to but not over the
      optic nerve head. CONCLUSIONS: We demonstrate a new method for following
      neurochemical changes at the retina with spatial resolution. This in vivo method
      is widely applicable to the site-specific study of states of normal and
      dysfunctional retinal neurochemistry.

PMID- 18079683
TI  - Regeneration of retinotectal projections after optic tectum removal in adult
      newts.
AB  - PURPOSE: When injured, the adult newt possesses the remarkable capability to
      regenerate tissues and organs with return of function and physiology. One example
      is the newt eye, in which regeneration can restore normal vision if the retina or
      lens has been removed. We wanted to examine how the retinotectal projections
      regenerate after removal of the brain's optic tectum and establish this animal as
      a model for retinal projection as well as a central nervous system regeneration
      model. METHODS: A major portion of the left optic tectum was removed in several
      adult newts, and the animals were monitored postoperatively for eight months to
      observe regeneration and innervation. Cell proliferation was examined by
      histological methods and by BrdU incorporation. RESULTS: We observed that adult
      newts have the capability to the excised optic tectum. As indicated by
      horseradish peroxidase staining, 80% of the retinotectal projection area was
      regenerated eight months after the operation, even though the wound closed much
      earlier. Our study provides the first quantitation of regeneration of the
      retinotectal projections. The ependymal cells that line the ventricle were the
      most likely source of the regenerated tectum. After removal, cell proliferation
      was detected only in the ependymal cells layer. Double staining of proliferating
      cells and neurons was limited, indicating that direct transition of ependymal
      cells is a possibility. CONCLUSIONS: The retinotectal projections after removal
      of the adult newt optic tectum can be readily re-established. Thus, this model
      can become indispensable for the study of vision restoration and neurogenesis.

PMID- 18079682
TI  - Ocular clusterin expression in von Hippel-Lindau disease.
AB  - PURPOSE: Clusterin is a multifunctional glycoprotein. Its mRNA is ubiquitously
      expressed, with high levels in von Hippel-Lindau (VHL) target organs such as the
      brain, liver, kidney, and adrenal medulla. Decreased clusterin secretion has been
      reported in renal cell carcinoma associated with VHL disease. The purpose of this
      study was to investigate ocular clusterin expression in VHL disease. METHODS:
      This retrospective case series included nine eyes with retinal
      hemangioblastoma/hemangioma associated with VHL disease, one eye from a patient
      with a history of VHL disease and central nervous system hemangioblastomas but
      without ocular lesions, one surgically-excised optic nerve with optic nerve
      hemangioblastoma/hemangioma, and three normal control eyes. Ocular specimens were
      evaluated by routine histology, immunohistochemistry for clusterin expression,
      and molecular detection of clusterin transcripts within ocular VHL
      hemangioblastomas compared with normal tissue from the same eye using
      microdissection and quantitative real-time PCR. RESULTS: All retinal
      hemangioblastoma were composed of typical VHL tumor cells admixed with small
      vascular channels as well as glial cells. Marked decrease of clusterin
      immunoreactivity was detected in all retinal hemangioblastoma and the optic nerve
      hemangioblastoma, whereas positive clusterin reactivity of the vascular and glial
      components was similar to that of normal retina. Quantitative real-time PCR
      analysis confirmed the decrease of clusterin mRNA in the VHL associated retinal
      hemangioblastoma and optic nerve hemangioblastoma in five cases. CONCLUSIONS:
      Clusterin shows possible important functions in tumor suppression by the VHL gene
      product (pVHL) and the potential to be a novel biomarker in retinal
      hemangioblastoma associated VHL disease. Further investigation of clusterin may
      provide better understanding of retinal hemangioblastoma associated with VHL
      disease.

PMID- 18079684
TI  - Suppression of keratoepithelin and myocilin by small interfering RNAs (siRNA) in
      vitro.
AB  - PURPOSE: Mutations of keratoepithelin (KE) and myocilin (MYOC) have been linked
      to certain types of inherited corneal stromal dystrophy and open-angle glaucoma,
      respectively. We investigated the potential use of small interfering RNAs
      (siRNAs) to suppress the expression of KE and MYOC and the related cytotoxicity
      of mutant myocilins in vitro. METHODS: cDNAs of the human keratoepithelin (KE)
      gene and myocilin (MYOC) gene were amplified by polymerase chain reaction and
      subcloned into pEGFP-N1 to construct respective plasmids, KEpEGFP and MYOCpEGFP,
      to produce fluorescence-generating fusion proteins. Short hairpin RNAs (shRNAs)
      were generated from an RNA polymerase III promoter-driven vector (pH1-RNA).
      Transformed HEK293 and trabecular meshwork (TM) cells were cotransfected via
      liposomes with either KEpEGFP or MYOCpEGFP and respective shRNA-generating
      plasmids to evaluate the suppression efficacy of shRNAs. Suppression of KE-EGFP
      fusion protein by KE-specific shRNAs was evaluated by fluorescence microscopy and
      western blotting. Suppression of MYOC-EGFP fusion protein by myocilin-specific
      shRNAs was quantified with UN-SCAN-IT software on digitized protein bands of
      western blots. The cellular stress response of TM cells induced by misfolded
      mutant myocilins was evaluated with a BiP promoter-driven luciferase reporter
      assay. RESULTS: One shRNA (targeting the coding sequence starting at 1,528 bp of
      KE) reduced the expression of KE-EGFP in HEK293 cells approximately by 50%
      whereas the other shRNA (targeting the 3'-UTR region of KE) suppressed more than
      80% of the expression of fusion protein. Cotransfection of MYOCpEGFP and various
      shRNA-generating plasmids targeting different regions of MYOC (containing amino
      acid residues R76, E352, K423, or N480 associated with inherited glaucoma) showed
      effective reduction of MYOC-EGFP fusion protein, ranged from 78% to 90% on
      average. The activation of the BiP gene (a cellular stress response induced by
      mutant myocilins) in transformed TM cells was significantly reduced when mutant
      myocilin proteins were suppressed by myocilin-specific shRNAs. CONCLUSIONS: KE
      specific or MYOC-specific shRNAs effectively suppressed the expression of
      recombinant KE or myocilin proteins and the related cytotoxicity of mutant
      myocilins in vitro. RNA interference may have future therapeutic implications in
      suppressing these genes.

PMID- 18079685
TI  - Human corneal epithelial cell proliferation by epiregulin and its cross-induction
      by other EGF family members.
AB  - PURPOSE: To investigate the effects of epiregulin, a newly identified member of
      the epidermal growth factor (EGF) family, on the proliferation of human corneal
      epithelial cells (HCECs). METHODS: The proliferation of HCECs was determined by
      cell counting and BrdU incorporation assays at specific times after exposure to
      different concentrations of human recombinant epiregulin (0 to 20 ng/ml).
      Immunohistochemical staining was used to localize epiregulin in cadaveric
      corneas. RT-PCR and real-time PCR were used to determine the expression levels of
      epiregulin in cultured and cadaveric HCECs. To examine the interaction between
      epiregulin and epidermal growth factor receptors (EGFRs), the phosphorylation of
      ErbB1 and ERK1/ERK2 (ERK1/2) was estimated by western blot analysis in the
      presence or absence of AG1478, a specific inhibitor of EGFR kinase activity. To
      search for cross-induction of epiregulin by other EGF family members, the
      expressions of EGF, heparin-binding epidermal growth factor-like growth factor
      (HB-EGF), amphiregulin (AR), and transforming growth factor-alpha (TGF-alpha)
      mRNA were determined by real-time PCR in the presence of 10 ng/ml of epiregulin.
      Conversely, the expression of epiregulin was also determined following the
      incubation of HCECs with 10 nM of either of EGF, HB-EGF, TGF-alpha, or AR.
      RESULTS: The mRNA of epiregulin was expressed in cultured HCECs and HCECs
      obtained from cadaveric eyes. Epiregulin was strongly detected in the limbal
      epithelium and basal epithelium of the peripheral cornea, but it was weakly
      detected in the central corneal epithelium. HCECs proliferated in the presence of
      epiregulin in a dose-dependent manner as detected by an increase in cell numbers
      or in BrdU incorporation. When HCECs were incubated with exogenous epiregulin,
      the expression of the mRNA of epiregulin was upregulated as detected by real-time
      PCR, and the phosphorylation of ErbB1 and ERK1/2 was upregulated in a dose
      dependent manner as shown by western blot analysis. These upregulations were
      inhibited by AG1478, a specific inhibitor of EGFR kinase activity. Epiregulin
      increased the expression of HB-EGF and AR, while TGF-alpha, HB-EGF, AR, and EGF
      increased the expression of epiregulin in HCECs. CONCLUSIONS: These findings
      indicate that epiregulin played an autocrine role in the proliferation of HCECs
      presumably through cross-induction with other EGF family members.

PMID- 18079686
TI  - A novel deletion variant of gammaD-crystallin responsible for congenital nuclear
      cataract.
AB  - PURPOSE: To investigate a novel deletion variant of gammaD-crystallin (CRYGD)
      identified in a Chinese family with nuclear congenital cataract. METHODS: A
      Chinese family with five affected members diagnosed with nuclear cataract and
      four unaffected members were recruited for the mutational screening of 15 known
      candidate genes for autosomal dominant congenital cataract. Two-point linkage
      analysis with single nucleotide polymorphism markers and microsatellite markers
      flanking these genes together with direct sequencing was applied to identify the
      disease-causing mutation. Recombinant NH(2)-terminal FLAG-tagged wildtype or
      mutant gammaD-crystallin was expressed in COS-7 cells. The expression pattern,
      protein solubility and intracellular distribution were analyzed by western
      blotting and confocal double immunofluorescence. RESULTS: Linkage analysis
      located the candidate region in the gammaC-crystallin and gammaD-crystallin gene
      cluster. Direct sequencing identified a c.494delG in CRYGD, which cosegregated
      with the disease in all affected members. Neither the unaffected family members
      nor the 103 unrelated controls carried this deletion mutation, which causes a
      frameshift and an early termination of polypeptide to become G165fs. A
      significantly reduced solubility was observed for this mutant. Unlike wildtype
      gammaD-crystallin, which existed in both the nucleus and cytoplasm, G165fs was
      colocalized with lamin A/C on the nuclear envelope. CONCLUSIONS: We have
      identified a novel mutation, c.494delG, in CRYGD, which was associated with
      nuclear cataract. This is the first deletion mutation of CRYGD found to cause
      autosomal dominant congenital cataract. The mutant protein with loss of
      solubility and localization to the nuclear envelope is hypothesized to impair
      nuclear transfiguration and degradation in lens fiber cell differentiation,
      leading to opacity formation during lens development.

PMID- 18079687
TI  - Apolipoprotein E gene and retinal microvascular signs in older people: the
      Cardiovascular Health Study.
AB  - PURPOSE: To examine the association between apolipoprotein E (APOE) gene
      polymorphism and retinal microvascular signs in an older population. METHODS:
      Retinal photographs were taken of 2,152 participants (1,831 whites, and 321
      African-Americans), aged 69-96 years, who were participating in a population
      based study of four United States communities. We used standardized protocols to
      assess photographs for the presence of retinal microvascular signs (retinopathy,
      arterio-venous nicking, and focal arteriolar narrowing) and a computer-assisted
      method to measure retinal vessel diameters. We analyzed DNA extracted from blood
      samples of participants for common allelic variants of the APOE gene. RESULTS:
      After adjusting for age, gender, systolic blood pressure, smoking, total serum
      cholesterol, and other risk factors, we found white participants carrying the
      epsilon2 and epsilon4 alleles were more likely to have arterio-venous nicking
      than the epsilon3/epsilon3 homozygotes, with odds ratio (OR) of 1.70 and
      confidence interval (CI) 95% (1.03-2.83) for the epsilon2 carriers and OR 1.74
      (95% CI 1.06-2.84) for the epsilon4 carriers. Among white participants without
      hypertension, the associations remained significant for the epsilon4 carriers (OR
      2.32, 95% CI 1.18-4.57). Whites, normotensive carriers of the epsilon2 allele had
      significantly narrower retinal arteriolar diameters (adjusted mean arteriolar
      diameter of 163.5 mum, 95% CI 160.1-167.0, p=0.03) compared to the
      epsilon3/epsilon3 homozygotes (167.8 mum, 95% CI 166.0-169.6). APOE gene
      polymorphism was not associated with retinopathy, focal narrowing, or retinal
      venular diameters in white participants. There were insufficient numbers of
      African-Americans for separate multivariate analysis. CONCLUSIONS: This study
      provides little evidence that the APOE gene polymorphism plays a significant role
      in the pathogenesis of retinal microvascular changes in the general population.
      In the older white population, APOE epsilon2 and epsilon4 allele carriers were
      more likely to have arterio-venous nicking. Other retinal signs, however, were
      not related to APOE gene polymorphism.

PMID- 18079689
TI  - A tag-single nucleotide polymorphisms approach to the vascular endothelial growth
      factor-A gene in age-related macular degeneration.
AB  - PURPOSE: Age-related macular degeneration (AMD) is the leading cause of poor
      vision in the developed world, and its pathogenesis remains unknown. The most
      devastating form of end stage disease is neovascular or wet AMD, where there is
      abnormal growth of new blood vessels under the retina. Vascular endothelial
      growth factor (VEGF) is thought to be a major player in the stimulus of this
      abnormal growth of blood vessels. We undertook a case-control association study
      to investigate the VEGF-A gene, a known angiogenic gene that has previously been
      associated with AMD. METHODS: We recruited 577 individuals with AMD (early,
      atrophic, and neovascular AMD) and 173 ethnically matched controls for our study.
      We employed a tag-single nucleotide polymorphisms (tSNP) approach to investigate
      this gene using a series of seven tSNPs that encompassed the coding region of the
      VEGF gene as well as its promoter. Alleles were determined by a MALDI-TOF based
      approach followed by statistical analysis. RESULTS: One SNP (rs3024997) showed
      evidence of departure from Hardy-Weinberg equilibrium in only the AMD cases.
      Therefore, it was retained for further analysis. All other SNPs in our study
      showed no departure from Hardy-Weinberg equilibrium. No association was found
      between any of the VEGF tSNPs analyzed in our study and AMD nor any of its sub
      types. CONCLUSIONS: Using a tSNP approach, we found no evidence of an association
      of these SNPs within the VEGF-A gene being associated with either AMD or any of
      its subtypes in our population.

PMID- 18079688
TI  - Voltage-gated sodium channel alpha-subunits Na(v)1.1, Na(v)1.2, and Na(v)1.6 in
      the distal mammalian retina.
AB  - PURPOSE: Recent studies indicate the presence of functional voltage-gated sodium
      channels (Na(v) channels) in the distal retina in several species. This study
      examined the distribution of Na(v) channels in the outer plexiform layer (OPL) of
      rat, mouse, and rabbit retinas. METHODS: Immunohistochemical and
      electroretinographic approaches were used. RESULTS: Antibodies specific for
      Na(v)1 alpha-subunits appropriately labeled retinal ganglion cells, their axons,
      and amacrine cells that are known to have tetrodotoxin (TTX)-sensitive Na(v)
      channels. Pan-Na(v), Na(v)1.2, and Na(v)1.6 labeling was found in horizontal
      cells and processes in all three species. Weaker Na(v)1.1 labeling was observed
      in rodent horizontal cells, but some rabbit horizontal cells and processes were
      prominently labeled. Additional labeling for Na(v)1.1, Na(v)1.2, and Na(v)1.6
      that was not attributable to horizontal cells was also present in the OPL. Much
      of this labeling was diffusely distributed. Some of the additional Na(v)1.1
      labeling was associated with photoreceptor terminals. By exclusion using
      photoreceptor and horizontal cell markers, some of this labeling could have been
      associated with bipolar cell dendrites, although colocalization was not directly
      established due to the diffuse nature of the labeling and limits on anatomical
      resolution. No Na(v)1 alpha-subunit labeling was observed in bipolar cell bodies.
      Testing for functional Na(v) channels was performed by recording full field flash
      electroretinograms from dark-adapted rats before and after intravitreal
      injections of TTX, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), or TTX+CNQX. TTX
      and CNQX+TTX, but not CNQX alone, greatly attenuated the dark-adapted cone-driven
      b-waves. CONCLUSIONS: Horizontal cells from three different mammalian retinas
      showed prominent labeling for Na(v)1 alpha-subunits. Some additional diffuse
      Na(v)1 alpha-subunit labeling in the OPL was associated with photoreceptor
      terminals. Na(v)1 alpha-subunit labeling also may have been present on bipolar
      cell dendrites, although it was not possible to establish this localization
      unequivocally by immunostaining. However, cone-driven b-waves in rats were
      reduced in maximum amplitude by TTX in the presence of CNQX which blocks synaptic
      input to horizontal, amacrine, and ganglion cells. This finding is consistent
      with TTX effects on the b-wave being due to blockade of Na(v) channels in cone
      bipolar cell dendrites in the OPL. The role of Na(v) channels in horizontal cells
      remains to be determined.

PMID- 18079690
TI  - Polymorphism of the endothelial nitric oxide synthase gene is associated with
      diabetic retinopathy in a cohort of West Africans.
AB  - PURPOSE: In addition to chronic hyperglycemia, there is increasing evidence that
      genetic factors may be important in the development of diabetes retinopathy (DR).
      Specifically, polymorphisms of the endothelial nitric oxide synthase gene (eNOS)
      have been reported to be associated with multiple health conditions including DR,
      hypertension, nephropathy, and cardiovascular diseases in several ethnic groups.
      However, there is a paucity of similar data in African Americans and other
      African populations. To address this issue, we investigated the potential
      association between polymorphisms of the eNOS gene and diabetes-related
      phenotypes in 384 persons with type 2 diabetes and 191 controls from two West
      African countries (Ghana and Nigeria). METHODS: We genotyped the
      deletion/insertion (4a/b) and the G894T polymorphisms of eNOS gene in a total of
      575 persons. RESULTS: The b/b genotype of the polymorphism was associated with a
      2.4 fold increased risk of DR (95% CI 1.39-4.09). In contrast, we did not observe
      any association between the genotypes or alleles of G894T polymorphism with DR,
      hypertension, or nephropathy. CONCLUSIONS: We observed a significant association
      between the 4a/b polymorphism of the eNOS and DR in our West African cohort.

PMID- 18079691
TI  - PLEKHA1-LOC387715-HTRA1 polymorphisms and exudative age-related macular
      degeneration in the French population.
AB  - PURPOSE: Identification of genetic factors for age-related macular degeneration
      (AMD) is of crucial importance in this common cause of blindness. Exudative AMD
      is rapidly progressive and usually associated with severe prognosis. Our purpose
      was to investigate this association on locus 10q26 in a case-control study
      including French patients specifically affected with exudative AMD. METHODS:
      Polymorphisms rs4146894:G>A of Pleckstrin Homology Domain-containing Protein
      Family A member 1 (PLEKHA1) gene, rs10490924:G>T at LOC387715, and rs11200638:G>A
      of HTRA1 (HTRA serine peptidase 1) gene were analyzed in AMD cases (n=118,
      age=72.3+/-3.8 years old) and healthy controls (n=116, age=72.0+/-3.8 years old).
      RESULTS: PLEKHA1 polymorphism was associated with AMD. The A allele frequency was
      0.67 in cases versus 0.41 in controls, (p=0.0001). After age and sex adjustment,
      the odds ratio for risk of AMD was 9.1 (4.0-20.9, 95% CI, p=0.0001) for the AA
      genotype and 2.6 (1.3-5.5, 95% CI, p=0.04) for the AG genotype, conditional on
      HTRA1. Association was even stronger and independent with HTRA1. The A allele
      frequency was 0.51 in cases versus 0.22 in controls, (p=0.0001). The odds ratio
      was 15.5 (5.5-43.9, 95% CI, p=0.0001) for the AA genotype and 3.4 (1.9-6.1, 95%
      CI, p=0.0001) for the AG genotype. No further information was obtained from
      LOC387715 due to virtually complete linkage disequilibrium with HTRA1
      polymorphism in cases (D'=1.0) and controls (D'=0.98). Although a role for
      PLEKHA1 could not be totally excluded, there was a four times higher AMD risk was
      associated with haplotype "A-T-A" involving "PLEKHA1-LOC387715-HTRA1" risk
      alleles. CONCLUSIONS: Compared to PLEKHA1, HTRA1/LOC387715 genetic variations
      were independently and strongly associated with exudative AMD in the French
      population. Chromosome-10 genetic variants appear as potentially useful risk
      markers for early detection of AMD.

PMID- 18079692
TI  - No association between OPA1 polymorphisms and primary open-angle glaucoma in
      three different populations.
AB  - PURPOSE: To investigate whether recently described polymorphisms in the optic
      atrophy 1 gene (OPA1) are associated with primary open-angle glaucoma (POAG) with
      elevated intraocular pressure in the Caucasian, African-American, and Ghanaian
      (West African) populations. METHODS: POAG was defined as the presence of
      glaucomatous optic nerve damage, associated visual field loss, and elevated
      intraocular pressure (>21 mm of mercury in both eyes). We used TaqMan allelic
      discrimination assays to genotype two single nucleotide polymorphisms (SNPs,
      rs10451941 and rs166850) in OPA1 in the Caucasian (279 cases, 227 controls),
      African American (193 cases, 97 controls), and Ghanaian (170 cases, 138 controls)
      populations. Allele, genotype, and haplotype frequencies were compared between
      the cases and controls from each population. RESULTS: There was no significant
      difference in OPA1 allele or genotype frequencies between POAG patients and
      controls at the rs10451941 and rs166850 SNPs in any population (p>0.05).
      Haplotype analysis also failed to demonstrate a significant association with
      POAG. The age-of-onset distribution in the Caucasian POAG patients was
      independent from genotypes at rs10451941. CONCLUSIONS: There was no association
      between two previously implicated OPA1 polymorphisms and a POAG phenotype that
      includes elevated intraocular pressure. This represents the first association
      analysis of OPA1 in high tension glaucoma in the African American and Ghanaian
      populations and is the largest study to date on the investigation of the
      potential association between OPA1 and POAG with elevated intraocular pressure.
      OPA1 association with POAG may be limited to patients with normal tension
      glaucoma in these populations.

PMID- 18079693
TI  - Frequency of CEP290 c.2991_1655A>G mutation in 175 Spanish families affected with
      Leber congenital amaurosis and early-onset retinitis pigmentosa.
AB  - PURPOSE: Leber congenital amaurosis (LCA) is the most severe inherited
      retinopathy with the earliest age of onset. To date, eleven genes have been
      reported to cause the non-syndromic LCA phenotype. The CEP290 gene has been shown
      to account for Joubert and Senior-Loken syndromes and to represent a frequent
      cause of non-syndromic LCA. The aim of the present study was to establish the
      prevalence of CEP290 c.2991_1655A>G in non-syndromic Spanish patients having LCA
      or early-onset retinitis pigmentosa (RP). METHODS: We used automated sequencing
      to examine 49 non-syndromic Spanish families with LCA and 126 Spanish families
      with early-onset RP for the CEP290 c.2991_1655A>G mutation. As a control, we
      recruited 50 unrelated Spanish healthy individuals. RESULTS: The frequencies of
      mutated alleles were 6% in LCA cases and 0% in early-onset RP and healthy
      individual controls. These results were compared to other populations.
      CONCLUSIONS: The CEP290 c.2991_1655A>G mutation frequency in Spanish non
      syndromic LCA families is lower than that of other countries.

PMID- 18079694
TI  - A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB
      activation.
AB  - Nod1 and Nod2 are intracellular proteins that are involved in host recognition of
      specific bacterial molecules and are genetically associated with several
      inflammatory diseases. Nod1 and Nod2 stimulation activates NF-kappaB through
      RICK, a caspase-recruitment domain-containing kinase. However, the mechanism by
      which RICK activates NF-kappaB in response to Nod1 and Nod2 stimulation is
      unknown. Here we show that RICK is conjugated with lysine-63-linked polyubiquitin
      chains at lysine 209 (K209) located in its kinase domain upon Nod1 or Nod2
      stimulation and by induced oligomerization of RICK. Polyubiquitination of RICK at
      K209 was essential for RICK-mediated IKK activation and cytokine/chemokine
      secretion. However, RICK polyubiquitination did not require the kinase activity
      of RICK or alter the interaction of RICK with NEMO, a regulatory subunit of
      IkappaB kinase (IKK). Instead, polyubiquitination of RICK was found to mediate
      the recruitment of TAK1, a kinase that was found to be essential for Nod1-induced
      signaling. Thus, RICK polyubiquitination links TAK1 to IKK complexes, a critical
      step in Nod1/Nod2-mediated NF-kappaB activation.

PMID- 18079695
TI  - Real-time detection reveals that effectors couple dynamin's GTP-dependent
      conformational changes to the membrane.
AB  - The GTPase dynamin is a mechanochemical enzyme involved in membrane fission, but
      the molecular nature of its membrane interactions and their regulation by guanine
      nucleotides and protein effectors remain poorly characterized. Using site
      directed fluorescence labeling and several independent fluorescence spectroscopic
      techniques, we have developed robust assays for the detection and real-time
      monitoring of dynamin-membrane and dynamin-dynamin interactions. We show that
      dynamin interacts preferentially with highly curved, PIP2-dense membranes and
      inserts partially into the lipid bilayer. Our kinetic measurements further reveal
      that cycles of GTP binding and hydrolysis elicit major conformational
      rearrangements in self-assembled dynamin that favor dynamin-membrane association
      and dissociation, respectively. Sorting nexin 9, an abundant dynamin partner,
      transiently stabilizes dynamin on the membrane at the onset of stimulated GTP
      hydrolysis and may function to couple dynamin's mechanochemical conformational
      changes to membrane destabilization. Amphiphysin I has the opposite effect. Thus,
      dynamin's mechanochemical properties on a membrane surface are dynamically
      regulated by its GTPase cycle and major binding partners.

PMID- 18079696
TI  - Two distinct mechanisms of silencing by the KvDMR1 imprinting control region.
AB  - Imprinting control regions (ICRs) are known to repress genes by utilizing one of
      two mechanisms, CTCF-mediated insulation or the transcription of non-coding RNAs
      (ncRNAs). The KvDMR1 ICR contains both the promoter for the Kcnq1ot1 ncRNA and
      two CTCF-binding sites located within sequences exhibiting repressive activity in
      enhancer-blocking assays. Deletion of KvDMR1 results in ubiquitous biallelic
      expression of eight maternal-specific genes in distal chromosome 7. Here we
      report that while truncation of the Kcnq1ot1 transcript results in the loss of
      imprinted expression of these genes in the placenta, it does not affect imprinted
      expression of Cdkn1c in a subset of embryonic tissues despite universal loss of
      paternal-specific methylation at Cdkn1c. Consistent with tissue-specific loss of
      imprinted expression, growth deficiency of these mutant mice was less severe than
      that observed previously in mice with deletion of KvDMR1. This study demonstrates
      that the KvDMR1 locus can silence Cdkn1c by a mechanism independent of Kcnq1ot1
      transcription, perhaps by CTCF-associated repression, making it the first example
      of an ICR capable of silencing the same gene by two distinct mechanisms.

PMID- 18079697
TI  - Intermediate-affinity LFA-1 binds alpha-actinin-1 to control migration at the
      leading edge of the T cell.
AB  - T lymphocytes use LFA-1 to migrate into lymph nodes and inflammatory sites. To
      investigate the mechanisms regulating this migration, we utilize mAbs selective
      for conformational epitopes as probes for active LFA-1. Expression of the KIM127
      epitope, but not the 24 epitope, defines the extended conformation of LFA-1,
      which has intermediate affinity for ligand ICAM-1. A key finding is that KIM127
      positive LFA-1 forms new adhesions at the T lymphocyte leading edge. This LFA-1
      links to the cytoskeleton through alpha-actinin-1 and disruption at the level of
      integrin or actin results in loss of cell spreading and migratory speed due to a
      failure of attachment at the leading edge. The KIM127 pattern contrasts with high
      affinity LFA-1 that expresses both 24 and KIM127 epitopes, is restricted to the
      mid-cell focal zone and controls ICAM-1 attachment. Identification of distinctive
      roles for intermediate- and high-affinity LFA-1 in T lymphocyte migration
      provides a biological function for two active conformations of this integrin for
      the first time.

PMID- 18079698
TI  - Cell cycle-specific UNG2 phosphorylations regulate protein turnover, activity and
      association with RPA.
AB  - Human UNG2 is a multifunctional glycosylase that removes uracil near replication
      forks and in non-replicating DNA, and is important for affinity maturation of
      antibodies in B cells. How these diverse functions are regulated remains obscure.
      Here, we report three new phosphoforms of the non-catalytic domain that confer
      distinct functional properties to UNG2. These are apparently generated by cyclin
      dependent kinases through stepwise phosphorylation of S23, T60 and S64 in the
      cell cycle. Phosphorylation of S23 in late G1/early S confers increased
      association with replication protein A (RPA) and replicating chromatin and
      markedly increases the catalytic turnover of UNG2. Conversely, progressive
      phosphorylation of T60 and S64 throughout S phase mediates reduced binding to RPA
      and flag UNG2 for breakdown in G2 by forming a cyclin E/c-myc-like phosphodegron.
      The enhanced catalytic turnover of UNG2 p-S23 likely optimises the protein to
      excise uracil along with rapidly moving replication forks. Our findings may aid
      further studies of how UNG2 initiates mutagenic rather than repair processing of
      activation-induced deaminase-generated uracil at Ig loci in B cells.

PMID- 18079699
TI  - Intrasplicing coordinates alternative first exons with alternative splicing in
      the protein 4.1R gene.
AB  - In the protein 4.1R gene, alternative first exons splice differentially to
      alternative 3' splice sites far downstream in exon 2'/2 (E2'/2). We describe a
      novel intrasplicing mechanism by which exon 1A (E1A) splices exclusively to the
      distal E2'/2 acceptor via two nested splicing reactions regulated by novel
      properties of exon 1B (E1B). E1B behaves as an exon in the first step, using its
      consensus 5' donor to splice to the proximal E2'/2 acceptor. A long region of
      downstream intron is excised, juxtaposing E1B with E2'/2 to generate a new
      composite acceptor containing the E1B branchpoint/pyrimidine tract and E2 distal
      3' AG-dinucleotide. Next, the upstream E1A splices over E1B to this distal
      acceptor, excising the remaining intron plus E1B and E2' to form mature E1A/E2
      product. We mapped branchpoints for both intrasplicing reactions and demonstrated
      that mutation of the E1B 5' splice site or branchpoint abrogates intrasplicing.
      In the 4.1R gene, intrasplicing ultimately determines N-terminal protein
      structure and function. More generally, intrasplicing represents a new mechanism
      by which alternative promoters can be coordinated with downstream alternative
      splicing.

PMID- 18079700
TI  - Cell-cycle regulation of cohesin stability along fission yeast chromosomes.
AB  - Sister chromatid cohesion is mediated by cohesin, but the process of cohesion
      establishment during S-phase is still enigmatic. In mammalian cells, cohesin
      binding to chromatin is dynamic in G1, but becomes stabilized during S-phase.
      Whether the regulation of cohesin stability is integral to the process of
      cohesion establishment is unknown. Here, we provide evidence that fission yeast
      cohesin also displays dynamic behavior. Cohesin association with G1 chromosomes
      requires continued activity of the cohesin loader Mis4/Ssl3, suggesting that
      repeated loading cycles maintain cohesin binding. Cohesin instability in G1
      depends on wpl1, the fission yeast ortholog of mammalian Wapl, suggestive of a
      conserved mechanism that controls cohesin stability on chromosomes. wpl1 is
      nonessential, indicating that a change in wpl1-dependent cohesin dynamics is
      dispensable for cohesion establishment. Instead, we find that cohesin stability
      increases at the time of S-phase in a reaction that can be uncoupled from DNA
      replication. Hence, cohesin stabilization might be a pre-requisite for cohesion
      establishment rather than its consequence.

PMID- 18079702
TI  - Imaging activation of adult-generated granule cells in spatial memory.
AB  - New neurons are continuously generated in the subgranular zone of the hippocampus
      throughout adulthood, and there is increasing interest as to whether these new
      neurons become functionally integrated into memory circuits. This protocol
      describes the immunohistochemical procedures to visualize the recruitment of new
      neurons into circuits supporting spatial memory in intact mice. To label adult
      generated granule cells, mice are injected with the proliferation marker 5-bromo
      2'-deoxyuridine (BrdU). At different delays after BrdU treatment, mice are
      trained to locate a hidden platform in the Morris water maze, and spatial memory
      can then be tested in a probe test with the platform removed from the pool.
      Ninety minutes after this probe test, mice are perfused and tissue is sectioned.
      Immunohistochemical procedures are used to quantify BrdU-labeled cells and
      expression of the immediate early gene, Fos. Because Fos expression is regulated
      by neuronal activity, the degree of overlap between BrdU-labeled and Fos-labeled
      neurons provides an indication of whether adult-generated granule neurons have
      been incorporated into spatial memory circuits.

PMID- 18079703
TI  - Measurement of cell proliferation by heavy water labeling.
AB  - DNA replication occurs almost exclusively during S-phase of the cell cycle and
      represents a simple biochemical metric of cell division. Previous methods for
      measuring cell proliferation rates have important limitations. Here, we describe
      experimental protocols for measuring cell proliferation and death rates based on
      the incorporation of deuterium ((2)H) from heavy water ((2)H(2)O) into the
      deoxyribose moiety of purine deoxyribonucleotides in DNA of dividing cells. Label
      incorporation is measured by gas chromatography/mass spectrometry. Modifications
      of the basic protocol permit analysis of small cell samples (down to 2,000
      cells). The theoretical basis and operational requirements for effective use of
      these methods to measure proliferation and death rates of cells in vivo are
      described. These methods are safe for use in humans, have technical and
      interpretation advantages over alternative techniques and can be used on small
      numbers of cells. The protocols enable definitive in vivo studies of the fraction
      or absolute number of newly divided cells and their subsequent survival kinetics
      in animals and humans.

PMID- 18079701
TI  - Sequential recruitment of the repair factors during NER: the role of XPG in
      initiating the resynthesis step.
AB  - To address the biochemical mechanisms underlying the coordination between the
      various proteins required for nucleotide excision repair (NER), we employed the
      immobilized template system. Using either wild-type or mutated recombinant
      proteins, we identified the factors involved in the NER process and showed the
      sequential comings and goings of these factors to the immobilized damaged DNA.
      Firstly, we found that PCNA and RF-C arrival requires XPF 5' incision. Moreover,
      the positioning of RF-C is facilitated by RPA and induces XPF release.
      Concomitantly, XPG leads to PCNA recruitment and stabilization. Our data strongly
      suggest that this interaction with XPG protects PCNA and Pol delta from the
      effect of inhibitors such as p21. XPG and RPA are released as soon as Pol delta
      is recruited by the RF-C/PCNA complex. Finally, a ligation system composed of
      FEN1 and Ligase I can be recruited to fully restore the DNA. In addition, using
      XP or trichothiodystrophy patient-derived cell extracts, we were able to diagnose
      the biochemical defect that may prove to be important for therapeutic purposes.

PMID- 18079704
TI  - Measurement of very low rates of cell proliferation by heavy water labeling of
      DNA and gas chromatography/pyrolysis/isotope ratio-mass spectrometric analysis.
AB  - DNA replication during S-phase represents a biochemical metric of cell division.
      We present here a protocol for measuring very low rates of cell proliferation, on
      the basis of the incorporation of deuterium ((2)H) from heavy water ((2)H(2)O)
      into the deoxyribose moiety of purine deoxyribonucleotides in DNA of dividing
      cells, by use of gas chromatography/pyrolysis/isotope ratio-mass spectrometry
      (GC/P/IRMS). Very low levels of label incorporation (>or=0.002% atom percent
      excess (2)H) can be quantified by GC/P/IRMS. This protocol thereby permits
      shorter periods or lower amounts of (2)H(2)O administration than would be
      required using standard GC/MS techniques for measuring cell proliferation
      kinetics (see accompanying protocol in this issue). A disadvantage of this
      approach compared to GC/MS is the requirement for larger numbers of cells (>
      approximately 10(7)). This protocol enables definitive in vivo studies of the
      fraction or absolute number of newly divided cells and their subsequent survival
      kinetics in animals and humans, even when turnover rates are very low. Indolent
      hematologic malignancies, such as chronic lymphocytic leukemia, and other
      relatively quiescent cells represent promising areas of application.

PMID- 18079705
TI  - Subtractive single-chain antibody (scFv) phage-display: tailoring phage-display
      for high specificity against function-specific conformations of cell membrane
      molecules.
AB  - Phage-display of antibody libraries is a powerful tool to select antibodies for
      specific epitopes. We describe a strategy for selecting highly specific scFv
      clones that discriminate between various conformational states of cell surface
      receptors. This approach adapts the M13 pIII phage-display technology toward a
      cell suspension-based strategy, which allows panning against complex, multimeric,
      fully functional cell membrane epitopes without alteration of structure due to
      purification or immobilization. As the functional properties are preserved, phage
      can be specifically depleted or selected for neo-epitopes exposed after
      physiological alterations of the targeted molecules. This subtractive strategy
      allows highly specific selection for single-chain antibodies directed against
      functionally regulated epitopes on the cell surface molecules that can be
      tailored for diagnostic and therapeutic applications. Using this protocol,
      activation-specific single-chain antibodies can be obtained within 4-6 weeks.

PMID- 18079706
TI  - Live imaging of epidermal morphogenesis during the development of the adult
      abdominal epidermis of Drosophila.
AB  - During larval stages of Drosophila development, the abdominal epidermis is
      composed of histoblasts (adult precursors) and larval epidermal cells (LECs).
      During metamorphosis, histoblasts proliferate and colonize the territories
      occupied by the LECs, which die and become engulfed by macrophages. This
      morphogenetic process is an excellent model for in vivo analysis of epithelial
      migration, cell division, cell death, patterning and differentiation. Here, we
      describe a protocol for time-lapse recording of the developing epidermis during
      metamorphosis. The protocol describes the removal of the pupal case (which acts
      as an opaque barrier to effective imaging) and mounting and imaging of specimens
      of different stages so that normal developmental processes are preserved. This
      method enables high-resolution studies over long time periods using fluorescent
      markers and confocal microscopy. The protocol requires 1 h for pupal dissection
      and mounting and, depending on the stages and genotypes to be analyzed, several
      more hours for preprocessing and aging and developmental staging of flies and
      pupae.

PMID- 18079707
TI  - Induction of pluripotent stem cells from fibroblast cultures.
AB  - Clinical application of embryonic stem (ES) cells faces difficulties regarding
      use of embryos, as well as tissue rejection after implantation. One way to
      circumvent these issues is to generate pluripotent stem cells directly from
      somatic cells. Somatic cells can be reprogrammed to an embryonic-like state by
      the injection of a nucleus into an enucleated oocyte or by fusion with ES cells.
      However, little is known about the mechanisms underlying these processes. We have
      recently shown that the combination of four transcription factors can generate ES
      like pluripotent stem cells directly from mouse fibroblast cultures. The cells,
      named induced pluripotent stem (iPS) cells, can be differentiated into three germ
      layers and committed to chimeric mice. Here we describe detailed methods and tips
      for the generation of iPS cells.

PMID- 18079708
TI  - Efficient transfection of DNA or shRNA vectors into neurons using magnetofection.
AB  - Efficient and long-lasting transfection of primary neurons is an essential tool
      for addressing many questions in current neuroscience using functional gene
      analysis. Neurons are sensitive to cytotoxicity and difficult to transfect with
      most methods. We provide a protocol for transfection of cDNA and RNA interference
      (short hairpin RNA (shRNA)) vectors, using magnetofection, into rat hippocampal
      neurons (embryonic day 18/19) cultured for several hours to 21 d in vitro. This
      protocol even allows double-transfection of DNA into a small subpopulation of
      hippocampal neurons (GABAergic interneurons), as well as achieving long-lasting
      expression of DNA and shRNA constructs without interfering with neuronal
      differentiation. This protocol, which uses inexpensive equipment and reagents,
      takes 1 h; utilizes mixed hippocampal cultures, a transfection reagent, CombiMag,
      and a magnetic plate; shows low toxicity and is suited for single-cell analysis.
      Modifications done by our three laboratories are detailed.

PMID- 18079709
TI  - The Bead blot: a method for selecting small molecule ligands for protein capture
      and purification.
AB  - We present a new method for selecting peptide ligands that are useful for protein
      purification, protein targeting and exploring protein-ligand interactions, and
      which requires no prior protein purification or derivatization. In the Bead blot,
      a complex mixture containing the target protein, for example, plasma, is
      incubated with a combinatorial library of peptide ligands synthesized on beads.
      The proteins are fractionated and purified on their respective ligands and the
      beads with their bound proteins are immobilized in a gel. The proteins are eluted
      from the ligands by capillary action and captured on a membrane so that their
      position on the membrane corresponds to the position of the beads in the gel. The
      protein is detected on the membrane, generating spots on an autoradiography film,
      the spots on the film are aligned with the beads in the gel, and the beads that
      bound the protein are recovered. The ligand on the bead(s) can be sequenced and
      synthesized at large scale for protein purification. The Bead blot can be
      completed in several hours with overnight pause steps if desired. On average, 5
      prospective ligands are selected per 50,000 beads screened using this method.
      Unlike other ligand identification methods, the target protein does not have to
      be purified or labeled, and the Bead blot allows ligands for multiple proteins to
      be selected in a single experiment.

PMID- 18079710
TI  - Assay for apoptosis using the mitochondrial probes, Rhodamine123 and 10-N-nonyl
      acridine orange.
AB  - Apoptosis plays a pivotal role in the regulation of cell turnover, and a defect
      or an excess of apoptosis has been implicated in several human diseases.
      Apoptosis is activated from an extracellular death signal, or from an internal
      pathway starting from the endoplasmatic reticulum or the mitochondria. To
      investigate the mitochondrial compartment during apoptosis, we have established a
      protocol using fluorochromes and flow cytometry to probe the structure and
      function of mitochondria kinetically. The protocol could be applied to whole
      cells or to isolated mitochondria. In the first case, cells are counterstained
      with ethidium bromide (EB) to evaluate plasma membrane function. The presence of
      the electrochemical gradient in the mitochondria is probed with Rhodamine123
      (Rh123), whereas the structure and the integrity of mitochondria are assessed
      using 10-N-nonyl-acridine orange (NAO). Not considering the time requested for
      cell/mitochondria preparation and the activation of apoptosis, the protocol lasts
      <1 h.

PMID- 18079711
TI  - Pd-catalyzed Suzuki-Miyaura reactions of aryl halides using bulky
      biarylmonophosphine ligands.
AB  - The following protocol describes the application of a highly active Pd-based
      catalyst system in the Suzuki-Miyaura cross-coupling reaction of arylboronic
      acids with aryl chlorides to provide biaryl compounds. The general procedure
      includes a detailed description of an appropriate reaction setup, two methods for
      assaying the crude reaction mixture (GC and TLC) and a procedure for the
      isolation, purification and characterization of the anticipated product. Reagents
      and catalyst precursors can be manipulated in the air; however, the cross
      coupling reactions must be performed in an inert atmosphere. Two Suzuki-Miyaura
      reactions are included in the text as representative examples of these
      procedures. Although the reactions can proceed in less than 5 min, the protocols,
      including workup, generally take 6-30 h to be completed.

PMID- 18079712
TI  - Synthesis of the 3'-thio-nucleosides and subsequent automated synthesis of
      oligodeoxynucleotides containing a 3'-S-phosphorothiolate linkage.
AB  - Oligodeoxynucleotides containing 3'-S-phosphorothiolate (3'-PS) linkages have
      become useful tools for probing enzyme-catalyzed cleavage processes in DNA. This
      protocol describes the synthesis of the phosphorothioamidite monomers derived
      from thymidine and 2'-deoxycytidine, and their application to a fully automated
      procedure for synthesising oligodeoxynucleotides containing 3'-PS linkages. The
      synthesis of the 5'-protected-3'-amidites is achievable in 2 weeks with the DNA
      synthesis and purification taking another 1 week.

PMID- 18079713
TI  - Profiling of microRNA expression by mRAP.
AB  - MicroRNA (miRNA) amplification profiling (mRAP) is a sensitive method for the
      determination of miRNA expression profiles. The method relies on a long,
      optimized 5' adaptor and the SMART (switching mechanism at the 5' end of RNA
      templates of reverse transcriptase) reaction to yield miRNA-derived cDNAs flanked
      by synthesized oligomers at each end. The cDNAs are PCR-amplified with primers
      corresponding to the oligomers, and the products are concatamerized for
      nucleotide sequencing. The expression level of each miRNA can be estimated from
      the frequency of the occurrence of its sequence in the data set, provided that
      sufficient clones of the cDNAs are sequenced. This method potentially yields
      millions of miRNA-derived clones from as few as 1 x 10(4) cells, thus allowing
      the characterization of miRNA expression profiles with small quantities of
      starting material such as those available for fresh clinical specimens or organs
      of developing embryos. This protocol can be completed in 10 d.

PMID- 18079714
TI  - Lung-directed gene therapy in mice using the nonviral Sleeping Beauty transposon
      system.
AB  - The Sleeping Beauty (SB) transposon is an integrative nonviral plasmid system.
      Here, we describe a protocol for SB-mediated transgene delivery using
      DNA/polyethyleneimine (PEI) complexes for long-term expression in mouse lungs.
      This protocol can be used for delivery of any plasmid-based vector system to
      mouse lungs, although long-term transgene expression will be obtained only when
      using the SB transposon or other integrating vector systems. The stages of this
      protocol are preparation of DNA-PEI complexes and injection of the complexes into
      the lateral tail vein of mice. We also provide protocols for assessing transgene
      expression using in vivo bioluminescence imaging and enzymatic assay of lung
      homogenates. The procedure can be completed within 24 h, starting from
      preparation of DNA-PEI complexes to analysis of transient transgene expression.

PMID- 18079716
TI  - Circular dichroism to determine binding mode and affinity of ligand-DNA
      interactions.
AB  - Circular dichroism (CD) is a useful technique for an assessment of DNA-binding
      mode, being a more accessible, low-resolution complement to NMR and X-ray
      diffraction methods. Ligand-DNA interactions can be studied by virtue of the
      interpretation of induced ligand CD signals resulting from the coupling of
      electric transition moments of the ligand and DNA bases within the asymmetric DNA
      environment. This protocol outlines methods to determine the binding mode and
      affinity of ligand-DNA interactions and takes approximately 7.5 h.

PMID- 18079715
TI  - Preferential delivery of the Sleeping Beauty transposon system to livers of mice
      by hydrodynamic injection.
AB  - Nonviral, DNA-mediated gene transfer is an alternative to viral delivery systems
      for expressing new genes in cells and tissues. The Sleeping Beauty (SB)
      transposon system combines the advantages of viruses and naked DNA molecules for
      gene therapy purposes; however, efficacious delivery of DNA molecules to animal
      tissues can still be problematic. Here we describe the hydrodynamic delivery
      procedure for the SB transposon system that allows efficient delivery to the
      liver in the mouse. The procedure involves rapid, high-pressure injection of a
      DNA solution into the tail vein. The overall procedure takes <1 h although the
      delivery into one mouse requires only a few seconds. Successful injections result
      in expression of the transgene in 5-40% of hepatocytes 1 d after injection.
      Several weeks after injection, transgene expression stabilizes at approximately
      1% of the level at 24 h, presumably owing to integration of the transposons into
      chromosomes.

PMID- 18079717
TI  - Single-cell isolation from cell suspensions and whole genome amplification from
      single cells to provide templates for CGH analysis.
AB  - A comprehensive genomic analysis of single cells is instrumental for numerous
      applications in tumor genetics, clinical diagnostics and forensic analyses. Here,
      we provide a protocol for single-cell isolation and whole genome amplification,
      which includes the following stages: preparation of single-cell suspensions from
      blood or bone marrow samples and cancer cell lines; their characterization on the
      basis of morphology, interphase fluorescent in situ hybridization pattern and
      antibody staining; isolation of single cells by either laser microdissection or
      micromanipulation; and unbiased amplification of single-cell genomes by either
      linker-adaptor PCR or GenomePlex library technology. This protocol provides a
      suitable template to screen for chromosomal copy number changes by conventional
      comparative genomic hybridization (CGH) or array CGH. Expected results include
      the generation of several micrograms of DNA from single cells, which can be used
      for CGH or other analyses, such as sequencing. Using linker-adaptor PCR or
      GenomePlex library technology, the protocol takes 72 or 30 h, respectively.

PMID- 18079718
TI  - Site-selective glycosylation of proteins: creating synthetic glycoproteins.
AB  - In higher organisms, the functions of many proteins are modulated by post
      translational modifications (PTMs). Glycosylation is by far the most diverse of
      the PTM processes. Natural protein production methods typically produce PTM or
      glycoform mixtures within which function is difficult to dissect or control.
      Chemical tagging methods allow the precise attachment of multiple glycosylation
      modifications to bacterially expressed (bare) protein scaffolds, allowing
      reconstitution of functionally effective mimics of glycoproteins in higher
      organisms. In this way combining chemical control of PTM with readily available
      protein scaffolds provides a systematic platform for creating probes of protein
      PTM interactions. This protocol describes the modification of Cys residues in
      proteins using glycomethanethiosulfonates and glycoselenenylsulfides and the
      modification of azidohomoalanine residues, introduced by Met replacement using
      auxotrophic Met(-) Escherichia coli strains, with glycoalkynes and the
      combination of these techniques for the creation of dual-tagged proteins. Each
      glycosylation procedure outlined in this protocol can be achieved in half a day.

PMID- 18079719
TI  - Synthesis of cationic single-isomer cyclodextrins for the chiral separation of
      amino acids and anionic pharmaceuticals.
AB  - We describe a protocol for the synthesis of mono-6(A)-(1-butyl-3-imidazolium)
      6(A)-deoxy-beta-cyclodextrin chloride (BIMCD), a cationic, water-soluble
      cyclodextrin used in the chiral separation of amino acids and anionic
      pharmaceuticals by capillary electrophoresis. Starting from commercially
      available chemicals, BIMCD is synthesized in five steps. The first step involves
      a nucleophilic substitution between p-toluenesulfonyl chloride and imidazole to
      afford 1-(p-toluenesulfonyl)imidazole (A). In the second step, a nucleophilic
      substitution between beta-cyclodextrin and A affords mono-6(A)-(p
      toluenesulfonyl)-6(A)-deoxy-beta-cyclodextrin (B). In the third step, a
      nucleophilic substitution between 1-bromobutane and imidazole affords 1
      butylimidazole (C). In the fourth step, a nucleophilic addition between A and C
      affords BIMCD tosylate. In the final step, anion exchange using an ion-exchange
      resin yields BIMCD as a highly water-soluble solid. Each step takes up to 2 d,
      including the time required for product purification. The overall protocol
      requires approximately 6 d.

PMID- 18079720
TI  - Tools for investigating peptide-protein interactions: peptide incorporation of
      environment-sensitive fluorophores via on-resin derivatization.
AB  - This protocol presents the peptide incorporation of environment-sensitive
      fluorophores derived from the dimethylaminophthalimide family. The procedure
      utilizes anhydride precursors of 4-dimethylaminophthalimide (4-DMAP) or 6
      dimethylaminonaphthalimide (6-DMN), whose syntheses are described in a related
      protocol from these authors. In this protocol, the fluorophores are directly
      incorporated after solid-phase peptide synthesis (SPPS) via on-resin
      derivatization of peptides prepared using commercially available diamino acids,
      which are Alloc-protected on the side-chain amino group. The time required to
      complete the procedure depends on the size and number of peptides targeted. As an
      alternative to this approach, the corresponding fluorescent amino acids can be
      obtained in an Fmoc-protected form for convenient use as building blocks in SPPS.
      This option is described in a related protocol by these authors.

PMID- 18079721
TI  - Tools for investigating peptide-protein interactions: peptide incorporation of
      environment-sensitive fluorophores through SPPS-based 'building block' approach.
AB  - This protocol presents the synthesis and peptide incorporation of environment
      sensitive fluorescent amino acids derived from the dimethylamino-phthalimide
      family. The procedure uses anhydride precursors of 4-dimethylaminophthalimide (4
      DMAP) or 6-dimethylaminonaphthalimide (6-DMN), whose syntheses are described in a
      related protocol by these authors. In this study, the corresponding fluorescent
      amino acids can be readily obtained in Fmoc-protected form for convenient use as
      building blocks in solid phase peptide synthesis (SPPS). The time required to
      complete the procedure depends on the size and the number of peptides targeted.
      Alternatively, the chromophores can be incorporated directly after SPPS via on
      resin derivatization of peptides, which is an option described in a related
      protocol by these authors.

PMID- 18079722
TI  - Synthesis of anhydride precursors of the environment-sensitive fluorophores 4
      DMAP and 6-DMN.
AB  - This protocol describes the synthesis of cyclic anhydride precursors of the
      environment-sensitive fluorophores 4-dimethylaminophthalimide (4-DMAP) and 6
      dimethylaminonaphthalimide (6-DMN). The condensation of these anhydrides with a
      primary amino group confers on molecules of interest solvatochromic properties.
      In particular, two strategies for the insertion of the chromophores into peptides
      are presented in two companion protocols. The anhydride syntheses can be
      completed on the gram scale in 2 d for the 4-DMAP precursor and 10-15 d for the 6
      DMN precursor.

PMID- 18079723
TI  - Construction and calibration of an optical trap on a fluorescence optical
      microscope.
AB  - The application of optical traps has come to the fore in the last three decades.
      They provide a powerful, sterile and noninvasive tool for the manipulation of
      cells, single biological macromolecules, colloidal microparticles and
      nanoparticles. An optically trapped microsphere may act as a force transducer
      that is used to measure forces in the piconewton regime. By setting up a well
      calibrated single-beam optical trap within a fluorescence microscope system, one
      can measure forces and collect fluorescence signals upon biological systems
      simultaneously. In this protocol, we aim to provide a clear exposition of the
      methodology of assembling and operating a single-beam gradient force trap
      (optical tweezers) on an inverted fluorescence microscope. A step-by-step guide
      is given for alignment and operation, with discussion of common pitfalls.

PMID- 18079724
TI  - Preparation of macromolecular complexes for cryo-electron microscopy.
AB  - This protocol describes the preparation of frozen-hydrated single-particle
      specimens of macromolecular complexes. First, it describes how to create a grid
      surface coated with holey carbon by first inducing holes in a Formvar film to act
      as a template for the holey carbon that is stable under cryo-electron microscopy
      (cryo-EM) conditions and is sample-friendly. The protocol then describes the
      steps required to deposit the homogeneous sample on the grid and to plunge-freeze
      the grid into liquid ethane at the temperature of liquid nitrogen, so that it is
      suitable for cryo-EM visualization. It takes 4-5 h to make several hundred holey
      carbon grids and about 1 h to make the frozen-hydrated grids. The time required
      for sample purification varies from hours to days, depending on the sample and
      the specific procedure required. A companion protocol details how to collect cryo
      EM data using an FEI Tecnai transmission electron microscope that can
      subsequently be processed to obtain a three-dimensional reconstruction of the
      macromolecular complex.

PMID- 18079725
TI  - Solid-phase peptide synthesis: from standard procedures to the synthesis of
      difficult sequences.
AB  - This protocol for solid-phase peptide synthesis (SPPS) is based on the widely
      used Fmoc/tBu strategy, activation of the carboxyl groups by aminium-derived
      coupling reagents and use of PEG-modified polystyrene resins. A standard protocol
      is described, which was successfully applied in our lab for the synthesis of the
      corticotropin-releasing factor (CRF), >400 CRF analogs and a countless number of
      other peptides. The 41-mer peptide CRF is obtained within approximately 80
      working hours. To achieve the so-called difficult sequences, special techniques
      have to be applied in order to reduce aggregation of the growing peptide chain,
      which is the main cause of failure for peptide chemosynthesis. Exemplary
      application of depsipeptide and pseudoproline units is shown for synthesizing an
      extremely difficult sequence, the Asn(15) analog of the WW domain FBP28, which is
      impossible to obtain using the standard protocol.

PMID- 18079726
TI  - Silencing of mammalian genes by tetracycline-inducible shRNA expression.
AB  - Conditional gene silencing in mammalian cells, via the controlled expression of
      short hairpin RNAs (shRNAs), is an effective method for studying gene function,
      particularly if the gene is essential for cell survival or development. Here we
      describe a simple and rapid protocol for the generation of tetracycline (Tet)
      inducible vectors that express shRNAs in a time- and dosage-dependent manner. Tet
      operator (TetO) sequences responsive to occupation by the Tet-repressor (TetR)
      were inserted at alternative positions within the wild-type H1 promoter and
      cloned into a eukaryotic expression vector. Additional cloning sites downstream
      of the promoter enable the insertion of shRNA sequences. This Tet-inducible shRNA
      expression system can be used for both transient and stable RNA interference
      (RNAi) approaches to control gene function in a spatiotemporal fashion. The
      entire protocol (preparation of constructs, generation of stable cell lines and
      functional analysis) can be completed in 3 months.

PMID- 18079727
TI  - Purification and characterization of transcribed RNAs using gel filtration
      chromatography.
AB  - RNA synthesis using in vitro transcription by phage T7 RNA polymerase allows
      preparation of milligram quantities of RNA for biochemical, biophysical and
      structural investigations. Previous purification approaches relied on gel
      electrophoretic or gravity-flow chromatography methods. We present here a
      protocol for the in vitro transcription of RNAs and subsequent purification using
      fast-performance liquid chromatography. This protocol greatly facilitates
      production of RNA in a single day from transcription to purification.

PMID- 18079728
TI  - Detecting protein-protein interactions by Far western blotting.
AB  - Far western blotting (WB) was derived from the standard WB method to detect
      protein-protein interactions in vitro. In Far WB, proteins in a cell lysate
      containing prey proteins are firstly separated by SDS or native PAGE, and
      transferred to a membrane, as in a standard WB. The proteins in the membrane are
      then denatured and renatured. The membrane is then blocked and probed, usually
      with purified bait protein(s). The bait proteins are detected on spots in the
      membrane where a prey protein is located if the bait proteins and the prey
      protein together form a complex. Compared with other biochemical binding assays,
      Far WB allows prey proteins to be endogenously expressed without purification.
      Unlike most methods using cell lysates (e.g., co-immunoprecipitation (co-IP)) or
      living cells (e.g., fluorescent resonance energy transfer (FRET)), Far WB
      determines whether two proteins bind to each other directly. Furthermore, in
      cases where they bind to each other indirectly, Far WB allows the examination of
      candidate protein(s) that form a complex between them. Typically, 2-3 d are
      required to carry out the experiment.

PMID- 18079729
TI  - Live imaging of synapse development and measuring protein dynamics using two
      color fluorescence recovery after photo-bleaching at Drosophila synapses.
AB  - Here we describe how to anesthetize and image Drosophila larvae as to follow 'the
      life history' of identified synapses and synaptic components. This protocol is
      sensitive, for example, the distribution of glutamate receptors expressed at
      physiological levels can be monitored. Typically, 2-20 time points can be
      recorded in the intact organism. Finally, we discuss how to extract the kinetic
      information on protein dynamics from two-color fluorescence recovery after photo
      bleaching (FRAP) measurements and give advice how to keep the in vivo imager's
      five arch enemies--limited temporal and spatial resolution, injury of the animal,
      inactivation of proteins and movement artifacts--in check. While we focus on
      synapses, as model structure, the protocol can easily be adapted to study other
      developmental processes such as muscle growth, gut development or tracheal
      branching.

PMID- 18079730
TI  - Thermodynamic constraints on methanogenic crude oil biodegradation.
AB  - Methanogenic degradation of crude oil hydrocarbons is an important process in
      subsurface petroleum reservoirs and anoxic environments contaminated with
      petroleum. There are several possible routes whereby hydrocarbons may be
      converted to methane: (i) complete oxidation of alkanes to H2 and CO2, linked to
      methanogenesis from CO2 reduction; (ii) oxidation of alkanes to acetate and H2,
      linked to acetoclastic methanogenesis and CO2 reduction; (iii) oxidation of
      alkanes to acetate and H2, linked to syntrophic acetate oxidation and
      methanogenesis from CO2 reduction; (iv) oxidation of alkanes to acetate alone,
      linked to acetoclastic methanogenesis and (v) oxidation of alkanes to acetate
      alone, linked to syntrophic acetate oxidation and methanogenesis from CO2
      reduction. We have developed the concept of a 'window of opportunity' to evaluate
      the range of conditions under which each route is thermodynamically feasible. On
      this basis the largest window of opportunity is presented by the oxidation of
      alkanes to acetate alone, linked to acetoclastic methanogenesis. This contradicts
      field-based evidence that indicates that in petroleum rich environments
      acetoclastic methanogenesis is inhibited and that methanogenic CO2 reduction is
      the predominant methanogenic process. Our analysis demonstrates that under those
      biological constraints oxidation of alkanes to acetate and H2, linked to
      syntrophic acetate oxidation and methanogenesis from CO2 reduction offers a
      greater window of opportunity than complete oxidation of alkanes to H2 and CO2
      linked to methanogenic CO2 reduction, and hence is the process most likely to
      occur.

PMID- 18079731
TI  - Diversity of cutaneous bacteria with antifungal activity isolated from female
      four-toed salamanders.
AB  - Among the microbiota of amphibian skin are bacteria that produce antifungal
      compounds. We isolated cutaneous bacteria from the skins of three populations of
      the nest-attending plethodontid salamander Hemidactylium scutatum and
      subsequently tested the bacterial isolates against two different fungi (related
      to Mariannaea elegans and Rhizomucor variabilis) that were obtained from dead
      salamander eggs. The culturable antifungal bacteria were phylogenetically
      characterized based on 16S rRNA phylogeny, and belonged to four phyla, comprising
      14 bacterial families, 16 genera and 48 species. We found that about half of the
      antifungal bacterial genera and families were shared with a related salamander
      species, but there was virtually no overlap at the species level. The proportion
      of culturable antifungal bacterial taxa shared between two large populations of
      H. scutatum was the same as the proportion of taxa shared between H. scutatum and
      Plethodon cinereus, suggesting that populations within a species have unique
      antifungal bacterial species. Approximately 30% of individuals from both
      salamander species carried anti-M. elegans cutaneous bacteria and almost 90% of
      P. cinereus and 100% of H. scutatum salamanders carried anti-R. variabilis
      cutaneous bacteria. A culture independent method (PCR/DGGE) revealed a shared
      resident bacterial community of about 25% of the entire resident bacterial
      community within and among populations of H. scutatum. Thus, the culturable
      antifungal microbiota was far more variable on salamander skins than was the
      bacterial microbiota detected by PCR/DGGE. The resident cutaneous antifungal
      bacteria may play an important role in amphibians' innate defense against
      pathogens, including the lethal chytrid fungus Batrachochytrium dendrobatidis.

PMID- 18079732
TI  - Induction of Toll-like receptor 2 and 4 expression on CD4+ and CD8+ T cells in G
      CSF-mobilized unrelated peripheral blood stem cell grafts during leukapheresis:
      impact on patient outcome.

PMID- 18079733
TI  - A prognostic score for patients with lower risk myelodysplastic syndrome.
AB  - Current prognostic models for myelodysplastic syndromes (MDS) do not allow the
      identification of patients with lower risk disease and poor prognosis that may
      benefit from early therapeutic intervention. We evaluated the characteristics of
      856 patients with low or intermediate-1 disease by the International Prognostic
      Scoring System. Mean follow-up was 19.6 months (range 1-262). Of these patients,
      87 (10%) transformed to acute myelogenous leukemia, and 429 (50%) had died. By
      multivariate analysis, characteristics associated with worse survival (P<0.01)
      were low platelets, anemia, older age, higher percent of marrow blasts and poor
      risk cytogenetics. Although not included in the model, higher ferritin (P=0.007)
      and beta2-microglobulin (P<0.001) levels were associated with worse prognosis.
      This allowed the development of a scoring system in which patients could be
      grouped in three categories: category 1 (n=182, 21%) with a median survival of
      80.3 months (95% CI 68-NA); category 2 (n=408, 48%) with a median survival of
      26.6 months (95% CI 22-32) and category 3 (n=265, 31%) with a median survival of
      14.2 months (95% CI 13-18). In summary, this analysis indicates that it is
      possible to identify patients with lower risk MDS and poor prognosis who may
      benefit from early intervention.

PMID- 18079734
TI  - MEF2C is activated by multiple mechanisms in a subset of T-acute lymphoblastic
      leukemia cell lines.
AB  - In T-cell acute lymphoblastic leukemia (T-ALL) the cardiac homeobox gene NKX2-5
      (at 5q35) is variously deregulated by regulatory elements coordinating with
      BCL11B (at 14q32.2), or the T-cell receptor gene TRD (at 14q11.2), respectively.
      NKX2-5 is normally expressed in developing spleen and heart, regulating
      fundamental processes, including differentiation and survival. In this study we
      investigated whether NKX2-5 expression in T-ALL cell lines reactivates these
      embryonal pathways contributing to leukemogenesis. Among 18 known targets
      analyzed, we identified three genes regulated by NKX2-5 in T-ALL cells, including
      myocyte enhancer factor 2C (MEF2C). Knockdown and overexpression assays confirmed
      MEF2C activation by NKX2-5 at both the RNA and protein levels. Direct
      interactions between NKX2-5 and GATA3 as indicated by co-immunoprecipitation data
      may contribute to MEF2C regulation. In T-ALL cell lines LOUCY and RPMI-8402 MEF2C
      expression was correlated with a 5q14 deletion, encompassing noncoding proximal
      gene regions. Fusion constructs with green fluorescent protein permitted
      subcellular detection of MEF2C protein in nuclear speckles interpretable as
      repression complexes. MEF2C consistently inhibits expression of NR4A1/NUR77,
      which regulates apoptosis via BCL2 transformation. Taken together, our data
      identify distinct mechanisms underlying ectopic MEF2C expression in T-ALL, either
      as a downstream target of NKX2-5, or via chromosomal aberrations deleting
      proximal gene regions.

PMID- 18079736
TI  - Monoallelic or biallelic LMO2 expression in relation to the LMO2 rearrangement
      status in pediatric T-cell acute lymphoblastic leukemia.

PMID- 18079735
TI  - Targeting 14-3-3 sensitizes native and mutant BCR-ABL to inhibition with U0126,
      rapamycin and Bcl-2 inhibitor GX15-070.
AB  - Small molecule tyrosine kinase inhibitors, such as imatinib, are effective
      therapies for BCR-ABL-mediated human leukemias. However, clinical drug resistance
      occurs, which warrants development of alternative and/or complementary
      therapeutic strategies to target critical downstream signaling molecules. We
      recently demonstrated that disrupting 14-3-3/ligand association by a peptide
      based 14-3-3 competitive antagonist R18 induces significant apoptosis, partially
      through reactivation of AKT-inhibited proapoptotic FOXO3a, in FGFR1 fusion
      transformed hematopoietic cells. Here, we report that targeting 14-3-3 by R18
      effectively induced significant apoptosis in Ba/F3 and K562 cells expressing BCR
      ABL, similarly through liberation and reactivation of FOXO3a. Moreover, R18
      sensitized BCR-ABL-transformed cells to inhibition with MEK1 inhibitor U0126, Bcl
      2 inhibitor GX15-070, or mTOR inhibitor rapamycin. Treatment with these reagents
      potentiated R18-induced reactivation of proapoptotic FOXO3a with enhanced
      expression of downstream transcription targets p27(kip1) and Bim1. Furthermore,
      R18-induced apoptotic cell death in cells expressing diverse imatinib-resistant
      BCR-ABL mutants, including T315I. This inhibition was enhanced by R18 in
      combination with U0126 and rapamycin. Thus, our findings suggest that targeting
      14-3-3 may potentiate the effects of conventional therapy for BCR-ABL-associated
      hematopoietic malignancies, and overcome drug resistance.

PMID- 18079737
TI  - Cell origin of pyothorax-associated lymphoma: a lymphoma strongly associated with
      Epstein-Barr virus infection.
AB  - Pyothorax-associated lymphoma (PAL) is an Epstein-Barr virus (EBV)-associated B
      cell lymphoma developing in the pleural cavity affected by chronic pyothorax. To
      clarify the cell origin of PAL, the expression of immunoglobulin heavy (IgH) and
      light chains in relation to somatic hypermutations (SHMs) of rearranged Ig heavy-
      and light-chain variable (IgV(H), IgV(L)) genes was examined using cell lines as
      well as clinical samples. SHMs without ongoing mutations of the IgV(H) gene were
      found in all PAL cell lines and clinical samples available for sequencing,
      indicating PAL to be derived from B cells at the postgerminal center (GC) stage
      of the differentiation process. They could be subdivided into post-GC cells with
      potentially productive IgV(H) genotypes (Group 1) and with sterile IgV(H)
      genotypes (Group 2). IgH expression was abrogated in Group 2 as expected and also
      in two cell lines in Group 1. DNA demethylation experiments with 5-aza-dC induced
      expression of IgH mRNA and protein in these cell lines. Most PAL cells were
      derived from crippled post-GC cells, which usually could not survive.
      Transformation of such B cells through EBV infection might provide a basis for
      the development of PAL with additional genetic changes.

PMID- 18079738
TI  - Targeting lipid metabolism by the lipoprotein lipase inhibitor orlistat results
      in apoptosis of B-cell chronic lymphocytic leukemia cells.
AB  - Constitutively activated pathways contribute to apoptosis resistance in chronic
      lymphocytic leukemia (CLL). Little is known about the metabolism of lipids and
      function of lipases in CLL cells. Performing gene expression profiling including
      B-cell receptor (BCR) stimulation of CLL cells in comparison to healthy donor
      CD5+ B cells, we found significant overexpression of lipases and phospholipases
      in CLL cells. In addition, we observed that the recently defined prognostic
      factor lipoprotein lipase (LPL) is induced by stimulation of BCR in CLL cells but
      not in CD5+ normal B cells. CLL cellular lysates exhibited significantly higher
      lipase activity compared to healthy donor controls. Incubation of primary CLL
      cells (n=26) with the lipase inhibitor orlistat resulted in induction of
      apoptosis, with a half-maximal dose (IC(50)) of 2.35 microM. In healthy B cells a
      significantly higher mean IC(50) of 148.5 microM of orlistat was observed, while
      no apoptosis was induced in healthy peripheral blood mononuclear cells (PBMCs;
      P<0.001). Orlistat-mediated cytotoxicity was decreased by BCR stimulation.
      Finally, the cytotoxic effects of orlistat on primary CLL cells were enhanced by
      the simultaneous incubation with fludarabine (P=0.003). In summary, alterations
      of lipid metabolism are involved in CLL pathogenesis and might represent a novel
      therapeutic target in CLL.

PMID- 18079739
TI  - The histone deacetylase inhibitor ITF2357 selectively targets cells bearing
      mutated JAK2(V617F).
AB  - We investigated the activity of ITF2357, a novel histone deacetylase inhibitor
      (HDACi) with antitumor activity, on cells carrying the JAK2(V617F) mutation
      obtained from polycythemia vera (PV) and essential thrombocythemia (ET) patients
      as well as the HEL cell line. The clonogenic activity of JAK2(V617F) mutated
      cells was inhibited by low concentrations of ITF2357 (IC(50) 0.001-0.01 microM),
      100- to 250-fold lower than required to inhibit growth of normal or tumor cells
      lacking this mutation. Under these conditions, ITF2357 allowed a seven fold
      increase in the outgrowth of unmutated over mutated colonies. By western blotting
      we showed that in HEL cells, ITF2357 led to the disappearance of total and
      phosphorylated JAK2(V617F) as well as pSTAT5 and pSTAT3, but it did not affect
      the wild-type JAK2 or STAT proteins in the control K562 cell line. By real-time
      PCR, we showed that, upon exposure to ITF2357, JAK2(V617F) mRNA was not modified
      in granulocytes from PV patients while the expression of the PRV-1 gene, a known
      target of JAK2, was rapidly downmodulated. Altogether, the data presented suggest
      that ITF2357 inhibits proliferation of cells bearing the JAK2(V617F) mutation
      through a specific downmodulation of the JAK2(V617F) protein and inhibition of
      its downstream signaling.

PMID- 18079740
TI  - JAK2 Mutations are present in all cases of polycythemia vera.

PMID- 18079741
TI  - The biology and future prospects of antivirulence therapies.
AB  - The emergence and increasing prevalence of bacterial strains that are resistant
      to available antibiotics demand the discovery of new therapeutic approaches.
      Targeting bacterial virulence is an alternative approach to antimicrobial therapy
      that offers promising opportunities to inhibit pathogenesis and its consequences
      without placing immediate life-or-death pressure on the target bacterium. Certain
      virulence factors have been shown to be potential targets for drug design and
      therapeutic intervention, whereas new insights are crucial for exploiting others.
      Targeting virulence represents a new paradigm to empower the clinician to prevent
      and treat infectious diseases.

PMID- 18079742
TI  - Drugs versus bugs: in pursuit of the persistent predator Mycobacterium
      tuberculosis.
AB  - Tuberculosis (TB) claims a life every 10 seconds and global mortality rates are
      increasing despite the use of chemotherapy. But why have we not progressed
      towards the eradication of the disease? There is no simple answer, although
      apathy, politics, poverty and our inability to fight the chronic infection have
      all contributed. Drug resistance and HIV-1 are also greatly influencing the
      current TB battle plans, as our understanding of their complicity grows. In this
      Review, recent efforts to fight TB will be described, specifically focusing on
      how drug discovery could combat the resistance and persistence that make TB
      worthy of the moniker 'The Great White Plague'.

PMID- 18079743
TI  - An integrated model of the recognition of Candida albicans by the innate immune
      system.
AB  - The innate immune response was once considered to be a limited set of responses
      that aimed to contain an infection by primitive 'ingest and kill' mechanisms,
      giving the host time to mount a specific humoral and cellular immune response. In
      the mid-1990s, however, the discovery of Toll-like receptors heralded a
      revolution in our understanding of how microorganisms are recognized by the
      innate immune system, and how this system is activated. Several major classes of
      pathogen-recognition receptors have now been described, each with specific
      abilities to recognize conserved bacterial structures. The challenge ahead is to
      understand the level of complexity that underlies the response that is triggered
      by pathogen recognition. In this Review, we use the fungal pathogen Candida
      albicans as a model for the complex interaction that exists between the host
      pattern-recognition systems and invading microbial pathogens.

PMID- 18079744
TI  - Phylogeny of the hair follicle: the sebogenic hypothesis.

PMID- 18079745
TI  - Human natural killer T cells infiltrate into the skin at elicitation sites of
      allergic contact dermatitis.
AB  - The purpose of this study is to identify invariant natural killer T cells (NKT
      cells) in cellular infiltrate of human allergic contact dermatitis (ACD) skin
      challenge sites. Skin biopsy specimens were taken from positive patch test
      reactions from 10 different patients (9 different allergens) and studied by
      immunochemistry, real-time PCR, nested PCR, and in situ hybridization to identify
      NKT cells and the cytokines associated with this cell type. Invariant NKT cells
      were identified in all the 10 skin biopsy specimens studied, ranging from 1.72 to
      33% of the cellular infiltrate. These NKT cells were activated in all cases, as
      they expressed cytokine transcripts for IFN-gamma and IL-4. Invariant NKT cells
      are present in ACD, regardless of the allergen that triggers the reaction, and
      are in an activated state. We conclude that innate immunity plays a role in late
      phases of type IV hypersensitivity reactions and may be responding to self-lipids
      released during allergic inflammation. These data complement the previous work by
      other investigators that suggest that NKT cells are important in the early
      cellular response during primary immune responses to allergens. Herein, it is
      demonstrated that NKT cells are constantly present during the late elicitation
      phase of human type IV hypersensitivity reactions.

PMID- 18079746
TI  - Protein therapeutics for junctional epidermolysis bullosa: incorporation of
      recombinant beta3 chain into laminin 332 in beta3-/- keratinocytes in vitro.
AB  - Junctional epidermolysis bullosa (JEB) is an inherited mechanobullous disease
      characterized by reduced adherence of the epidermal keratinocytes to the
      underlying dermis, and is often caused by the absence of functional laminin 332
      due to the lack or dysfunction of its beta3 chain. As there are no specific
      therapies for JEB, we tested whether a protein replacement strategy could be
      applicable for the restoration of the laminin 332 assembly and reversion of the
      JEB phenotype in human keratinocytes that lack beta3 subunit. Here, we developed
      the protocol for production and purification of the biologically active
      recombinant beta3 chain. Next, we demonstrated that delivery of recombinant beta3
      polypeptide into the endoplasmic reticulum of the immortalized beta3-null
      keratinocytes led to the restoration of the laminin 332 assembly, secretion, and
      deposition into the basement membrane zone, as confirmed by Western blot
      analysis, confocal immunofluorescent microscopy in vitro, and on cultured
      organotypic human JEB skin reconstructs. Although the amount of laminin 332
      produced by protein-treated beta3-null keratinocytes is lower than that in normal
      human keratinocytes, our results demonstrate the applicability of the recombinant
      proteins for JEB treatment and open new perspectives for the development of novel
      therapeutics for this inherited, currently intractable, skin disorder.

PMID- 18079747
TI  - The IgE-reactive autoantigen Hom s 2 induces damage of respiratory epithelial
      cells and keratinocytes via induction of IFN-gamma.
AB  - Hom s 2, the alpha-chain of the nascent polypeptide-associated complex, is an
      intracellular autoantigen that has been identified with IgE autoantibodies from
      atopic dermatitis patients. We investigated the humoral and cellular immune
      response to purified recombinant Hom s 2 (rHom s 2). rHom s 2 exhibited IgE
      reactivity comparable to exogenous allergens, but did not induce relevant
      basophil cell degranulation. The latter may be attributed to the fact that
      patients recognized single epitopes on Hom s 2 as revealed by IgE epitope mapping
      with rHom s 2 fragments. In contrast to exogenous allergens, rHom s 2 had the
      intrinsic ability to induce the release of IFN-gamma in cultured peripheral blood
      mononuclear cells from atopic as well as non-atopic individuals. IFN-gamma
      containing culture supernatants from Hom s 2-stimulated peripheral blood
      mononuclear cells caused disintegration of respiratory epithelial cell layers and
      apoptosis of skin keratinocytes, which could be inhibited with a neutralizing
      anti-IFN-gamma antibody. Our data demonstrate that the Hom s 2 autoantigen can
      cause IFN-gamma-mediated cell damage.

PMID- 18079748
TI  - Polymorphism patterns in the promoter region of the MC1R gene are associated with
      development of freckles and solar lentigines.

PMID- 18079749
TI  - Identification of a genetic locus for ichthyosis vulgaris on chromosome 10q22.3
      q24.2.
AB  - Ichthyosis vulgaris (IV) is one of the most commonly inherited disorders and has
      an estimated prevalence rate of 2.29% in China. To date, only one gene
      responsible for IV, the filaggrin gene (FLG), was identified, but genetic
      heterogeneity exists. In this study, two Chinese families with autosomal-dominant
      IV were genetically characterized. The FLG gene was first excluded as the disease
      causing gene in the two families. The larger family was then characterized by
      genome-wide linkage analysis to identify a new genetic locus for IV. Significant
      linkage was identified with markers on chromosome 10q22.3-q24.2 with a maximum
      LOD score of 3.19. No other markers showed a LOD score of >1.5. Fine mapping
      defined the new genetic locus within a 20.7 cM region between markers D10S569 and
      D10S1709. The second family also showed positive linkage to the same 10q22.3
      q24.2 region. The combined maximum LOD score in the two families was 3.95.
      Identification of linkage in two independent families provides strong genetic
      evidence that a previously unreported gene for IV is located on chromosome
      10q22.3-q24.2. Future studies of the candidate genes at the 10q IV locus will
      identify a specific gene, which will provide insights into the pathogenesis of
      IV.

PMID- 18079750
TI  - Plakophilin-3-deficient mice develop hair coat abnormalities and are prone to
      cutaneous inflammation.
AB  - We generated mice deficient in plakophilin-3 (PKP3), a member of the Armadillo
      repeat family and a component of desmosomes and stress granules in epithelial
      cells. In these mice, several subsets of hair follicles (HFs) had morphological
      abnormalities, and the majority of awl and auchene hair shafts had fewer medullar
      air columns. Desmosomes were absent from the basal layer of the outer root sheath
      of HFs and from the matrix cells that are in contact with dermal papillae. In the
      basal layer of PKP3-null epidermis, densities of desmosomes and adherens
      junctions were remarkably altered. Compensatory changes in several junctional
      proteins were observed. PKP3-null mice housed in conventional facilities were
      prone to dermatitis. Our animal model provides in vivo evidence that PKP3 plays a
      critical role in morphogenesis of HFs and shafts and in limiting inflammatory
      responses in the skin.

PMID- 18079751
TI  - IGF1 promotes resistance to apoptosis in melanoma cells through an increased
      expression of BCL2, BCL-X(L), and survivin.
AB  - IGF1 plays a key role in the development and growth of multiple tumors and in the
      prevention of apoptosis. In melanoma cells, IGF1 has been shown to mediate
      resistance to anoikis-induced apoptosis. However, the effect of IGF1 on other
      proapoptotic stimuli has never been reported. Further, the molecular mechanisms
      by which IGF1 mediates its prosurvival properties in melanoma cells remain
      unknown. Here, we demonstrate that IGF1 impairs the onset of tumor necrosis
      factor-related apoptosis-inducing ligand and staurosporine-induced apoptosis in
      melanoma cells expressing either wild-type or oncogenic B-Raf. Further, we show
      that IGF1 inhibits mitochondrial damage that occurs during apoptosis, thereby
      indicating that IGF1 acts at the level of mitochondria to mediate its
      antiapoptotic stimuli. Accordingly, IGF1 increases the mRNA levels and protein
      expression of antiapoptotic members of the BCL2 family--BCL2 and BCL-X(L)--and
      that of the inhibitor of apoptosis protein, survivin. Further, their specific
      silencing by small interfering RNA prevents the protective effect of IGF1. These
      findings therefore delineate the molecular mechanisms by which IGF1 mediates its
      prosurvival properties and provide a basis for clinical strategies designed to
      neutralize IGF1 or its target genes.

PMID- 18079752
TI  - Single-strand DNA-mediated targeted mutagenesis of genomic DNA in early mouse
      embryos is stimulated by Rad51/54 and by Ku70/86 inhibition.
AB  - Low and variable efficiency is a major problem in targeted gene alteration, which
      is used as a primary tool in gene therapy and animal model studies. We tested
      several types of constructs alone, or in combination with other factors, to
      introduce a point mutation into the alphaB-crystallin gene in one-celled mouse
      embryos. We found that co-injection of ssDNA along with antibodies against
      Ku70/86, or supplementing the system with hRad51/hRad54, increases efficiency of
      targeted mutagenesis. These findings suggest that proteins in the homologous
      recombination DNA repair pathway contribute, and that proteins involved in the
      alternative nonhomologous end-joining pathway inhibit, ssDNA-mediated targeted
      mutagenesis. This is the first successful demonstration of targeted mutation in
      early mouse embryos. This novel methodology of supplying protein factors to
      stimulate gene modification in the nucleus has not been previously reported.

PMID- 18079753
TI  - Escherichia coli nitroreductase plus CB1954 enhances the effect of radiotherapy
      in vitro and in vivo.
AB  - Escherichia coli nitroreductase (NTR) converts the prodrug CB1954 (5-(aziridin-1
      yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent that causes DNA
      crosslinks. In this study, the ability of NTR to enhance the combined effects of
      CB1954 and radiation has been tested in vitro and in vivo. Stably transduced
      ovarian cancer cells (SKOV3-NTR) that are sensitive to CB1954 (IC(50)=0.35 muM)
      demonstrated enhanced cytotoxicity when treated with CB1954 and single-fraction
      irradiation. The NTR-CB1954 system mediated a bystander effect in combination
      with radiation on transfer of conditioned medium from SKOV3-NTR, but not SKOV3,
      cells to SW480 target cells. The ability of CB1954 to enhance radiation-induced
      cytotoxicity in SKOV3-NTR (but not SKOV3) cells was also demonstrated by
      fluorescence-activated cell sorting (FACS) with dual staining for propidium
      iodide/fluorescein diacetate, 4',6-diamidino-2-phenylindole dichloride staining
      of apoptotic cells and measurement of double-stranded DNA breaks by FACS and
      confocal microscopy for gammaH2AX foci. Adenoviral delivery of NTR, under
      constitutive cytomegalovirus or tissue-specific CTP1 promoters, increased the in
      vitro cytotoxicity of CB1954 plus radiation in MTT and clonogenic assays.
      Finally, adenoviral delivery of NTR plus CB1954 enhanced the effect of
      fractionated radiotherapy (12 Gy in four fractions) in SW480 xenograft tumours in
      nude mice.

PMID- 18079754
TI  - Vascular endothelial growth factor reduced hypoxia-induced death of human
      myoblasts and improved their engraftment in mouse muscles.
AB  - Muscle precursor cell (myoblasts) transplantation is considered as a potential
      approach to restore dystrophin expression in Duchenne muscular dystrophy (DMD)
      patients. The study purpose was to verify the implication of hypoxia in the
      myoblast death observed after their transplantation and also to evaluate the
      potential beneficial effects of vascular endothelial growth factor (VEGF)
      overexpression on myoblast engraftment in a murine model. Pimonidazole
      hydrochloride (hypoxyprobe-1) was used to mark selectively myoblasts to evaluate
      their hypoxia in vivo. In vitro, hypoxia was induced by culturing human myoblasts
      in hypoxic environment. In vitro effects of VEGF(165) on survival of human cells
      was assessed by Hoescht-PI labeling. Tibialis anterior (TA) female mouse muscles
      were electroporated with a plasmid containing the VEGF(165) or with an empty
      vector. Circulating VEGF concentration was assessed by ELISA. After 2 weeks of
      electroporation, severe combined immunodeficient (SCID) mice were transplanted
      with 800 000 human male myoblasts labeled with radioactive thymidine. Mouse
      muscles were harvested 2 and 4 days later and myoblast survival and proliferation
      were evaluated by scintigraphy and Y chromosome quantitative PCR. The long-term
      graft success was evaluated using gamma-radiograph imaging and by counting the
      dystrophin positive muscle fibers. Hypoxyprobe labeling has shown that most of
      the transplanted myoblasts were hypoxic. The transplantation of radioactive male
      myoblasts in female mice electroporated with the VEGF(165) plasmid demonstrated
      that VEGF reduced their death by 10% but did not improve their proliferation.
      VEGF(165) enhanced human myoblast survival in vitro under hypoxic conditions.
      Electroporation of TA muscles of SCID mouse with the vector coding for VEGF(165)
      promoted angiogenesis and improved by 1.5-fold the success of myoblast
      transplantation in comparison with the control mice that were electroporated with
      the empty vector. These results indicate that hypoxia is partially responsible
      for the death of the transplanted myoblasts. VEGF can be used to improve myoblast
      survival and the graft success.

PMID- 18079755
TI  - Microscopic imaging techniques for drug discovery.
AB  - Microscopic imaging can enhance the drug discovery process by helping to describe
      how disease processes unfold and how potential therapies might intervene.
      Recently introduced technologies, and enhancements to existing techniques, are
      addressing technical issues that have limited the usefulness of microscopic
      imaging in the past. In particular, these innovations are improving spatial
      resolution, increasing tissue penetration, overcoming physical access issues and
      enhancing experimental throughput. Notable recent trends, which are discussed in
      this article, include the development of super-resolution microscopes, the
      incorporation of multiphoton techniques into intravital and fibre-optic
      microscopy and the automation of microscopy and image analysis for high-content
      screening. Together, these developments are augmenting the existing assays and
      disease models that are used in early drug discovery and, in some cases, enabling
      new ones.

PMID- 18079756
TI  - Derive and conquer: sourcing and differentiating stem cells for therapeutic
      applications.
AB  - Although great progress has been made in the isolation and culture of stem cells,
      the future of stem-cell-based therapies and their productive use in drug
      discovery and regenerative medicine depends on two key factors: finding reliable
      sources of multipotent and pluripotent cells and the ability to control their
      differentiation to generate desired derivatives. It is essential for clinical
      applications to establish reliable sources of pathogen-free human embryonic stem
      cells (ESCs) and develop suitable differentiation techniques. Here, we address
      some of the problems associated with the sourcing of human ESCs and discuss the
      current status of stem-cell differentiation technology.

PMID- 18079757
TI  - Impact of lipoproteins on the biological activity and disposition of hydrophobic
      drugs: implications for drug discovery.
AB  - In contrast to many traditional pharmaceutical agents that exhibit a high degree
      of aqueous solubility, new drug candidates are frequently highly lipophilic
      compounds. The aqueous environment of the blood provides a thermodynamically
      unfavourable environment for the disposition of such hydrophobic drugs. However,
      this limitation can be overcome by association with circulating lipoproteins.
      Elucidation of the mechanisms that dictate drug-lipoprotein association and blood
      to-tissue partitioning of lipoprotein encapsulated drugs might yield valuable
      insight into the factors governing the pharmacological activity and potential
      toxicity of these compounds. This Review discusses the impact of hydrophobic drug
      lipoprotein interactions on pharmacokinetics, drug metabolism, tissue
      distribution and biological activity of various hydrophobic compounds, and
      outlines how best to use this information in drug discovery and development
      programmes.

PMID- 18079759
TI  - Influence of exposure error and effect modification by socioeconomic status on
      the association of acute cardiovascular mortality with particulate matter in
      Phoenix.
AB  - Using ZIP code-level mortality data, the association of cardiovascular mortality
      with PM(2.5) and PM(10-2.5), measured at a central monitoring site, was
      determined for three populations at different distances from the monitoring site
      but with similar numbers of deaths and therefore similar statistical power. The %
      risk and statistical significance for the association of mortality with PM(2.5)
      fell off with distance from the monitor, as would be expected if exposure error
      increased with distance. However, the % risk for PM(10-2.5) increased in going
      from the population in Central Phoenix, where the monitoring site was located, to
      a population in a Middle Ring around Phoenix and fell off in an Outer Ring
      population. The % risks for the Outer Ring were low for each of the six lag days
      (0-5) and for the 6-day moving average. The lag structures for PM(2.5) and PM(10
      2.5) also differed for the Central Phoenix and Middle Ring populations. These
      differences led us to examine the socioeconomic status (SES) of the populations.
      On the basis of education and income, the population in Central Phoenix had a
      lower SES than the Middle Ring. Thus, the differences between Central Phoenix and
      the Middle Ring may be due to effect modification by SES and differences in
      exposure error. However, the effect modification by SES may be different for
      thoracic coarse particulate matter (PM) than for fine PM. This study provides new
      information on the association of PM(10-2.5) with cardiovascular mortality. In
      the Middle Ring, the % risk per 10 microg/m3 increase in PM(10-2.5) concentration
      (lower and upper 95% confidence levels) for lag day 1 was 3.4 (1.0, 5.8) and for
      the 6-day distributed-lag was 3.8 (0.3, 7.5). The differences in lag structure
      for PM(2.5) and PM(10-2.5) provide evidence that the two particle size classes
      have health effects that are different and independent. This study also helps
      explain the high % risks for PM(2.5) found for Central Phoenix, 6.6 (1.1, 12.5)
      for lag day 1, and 11.5 (2.8, 20.9) for the 6-day moving average. The smaller
      area may have a lower exposure error, and the lower SES population may be more
      susceptible to fine PM as compared to the larger areas and more heterogeneous
      populations used in many studies.

PMID- 18079760
TI  - Effects of exposure measurement error on particle matter epidemiology: a
      simulation using data from a panel study in Baltimore, MD.
AB  - Ascertaining the true risk associated with exposure to particulate matter (PM) is
      difficult, given the fact that pollutant components are frequently correlated
      with each other and with other gaseous pollutants; relationships between ambient
      concentrations and personal exposures are often not well understood; and PM,
      unlike its gaseous co-pollutants, does not represent a single chemical. In order
      to examine differences between observed versus true health risk estimate from
      epidemiologic studies, we conducted a simulation using data from a recent multi
      pollutant exposure assessment study in Baltimore, MD. The objectives of the
      simulation were twofold: (a) to estimate the distribution of personal air
      pollutant exposures one might expect to observe within a population, given the
      corresponding ambient concentrations found in that location and; (b) using an
      assumed true health risk with exposure to one pollutant, to estimate the
      distribution of health risk estimates likely to be observed in an epidemiologic
      study using ambient pollutant concentrations as a surrogate of exposure as
      compared with actual personal pollutant exposures. Results from the simulations
      showed that PM2.5 was the only pollutant where a true association with its total
      personal exposures resulted in a significant observed association with its
      ambient concentrations. The simulated results also showed that true health risks
      associated with personal exposure to O3 and NO2 would result in no significant
      observed associations with any of their respective ambient concentrations.
      Conversely, a true association with PM2.5 would result in a significant, observed
      association with NO2 (beta=0.0115, 95% confidence interval (CI): 0.0056, 0.0185)
      and a true association with exposure to SO4(2-) would result in an observed
      significant association with O3 (beta=0.0035, 95% CI: 0.0021, 0.0051) given the
      covariance of the ambient pollutant concentrations. The results provide an
      indication that, in Baltimore during this study period, ambient gaseous
      concentrations may not have been adequate surrogates for corresponding personal
      gaseous exposures to allow the question to be investigated using central site
      monitors. Alternatively, the findings may suggest that in some locations,
      observed associations with the gaseous pollutants should be interpreted with
      caution, as they may be reflecting associations with PM or one of its chemical
      components.

PMID- 18079761
TI  - Controlling for confounding in the presence of measurement error in hierarchical
      models: a Bayesian approach.
AB  - A major concern in studies that address the health effects of air pollution is
      whether an observed association between concentrations of a pollutant and a
      health outcome is all, or in part, due to the correlation between that exposure
      and either a second pollutant or a confounder. The addition of exposure
      measurement error to such data complicates matters further. To account for
      measurement error when data come from a multi-city study, Schwartz and Coull
      (2003) proposed a two-stage estimator. These authors showed via both first
      principles and simulation that their approach yields unbiased estimates for the
      parameters of interest. However, these estimates have large variability. In this
      paper, we describe a fully Bayesian approach that yields estimators that are much
      more efficient than the existing two-stage measurement error correction yet still
      unbiased. The proposed approach can also incorporate additional exposures or
      confounders without requiring strict assumptions that are necessary in existing
      formulations of the model. We compare the properties of the Bayesian estimators
      to existing approaches via simulation.

PMID- 18079762
TI  - Multipollutant modeling issues in a study of ambient air quality and emergency
      department visits in Atlanta.
AB  - Multipollutant models are frequently used to differentiate roles of multiple
      pollutants in epidemiologic studies of ambient air pollution. In the presence of
      differing levels of measurement error across pollutants under consideration,
      however, they can be biased and as misleading as single-pollutant models. Their
      appropriate interpretation depends on the relationships among the pollutant
      measurements and the outcomes in question. In situations where two or more
      pollutant variables may be acting as surrogates for the etiologic agent(s),
      multipollutant models can help identify the best surrogate, but the risk
      estimates may be influenced by inclusion of a second variable that is not itself
      an independent risk factor for the outcome in question. In this paper, these
      issues will be illustrated in the context of an ongoing study of emergency visits
      in Atlanta. Emergency department visits from 41 of 42 hospitals serving the 20
      county Atlanta metropolitan area for the period 1993-2004 (n=10,206,389 visits)
      were studied in relation to ambient pollutant levels, including speciated
      particle measurements from an intensive monitoring campaign at a downtown station
      starting in 1998. Relative to our earlier publications, reporting results through
      2000, the period for which the speciated data are available is now tripled (6
      years in length). Poisson generalized linear models were used to examine outcome
      counts in relation to 3-day moving average concentrations of pollutants of a
      priori interest (ozone, nitrogen dioxide, carbon monoxide, sulfur dioxide,
      oxygenated hydrocarbons, PM10, coarse PM, PM2.5, and the following components of
      PM2.5: elemental carbon, organic carbon, sulfate, and water-soluble transition
      metals). In the present analysis, we report results for two outcome groups: a
      respiratory outcomes group and a cardiovascular outcomes group. For
      cardiovascular visits, associations were observed with CO, NO2, and PM2.5
      elemental carbon and organic carbon. In multipollutant models, CO was the
      strongest predictor. For respiratory visits, associations were observed with
      ozone, PM10, CO, and NO2 in single-pollutant models. In multipollutant models,
      PM10 and ozone persisted as predictors, with ozone the stronger predictor.
      Caveats and considerations in interpreting the multipollutant model results are
      discussed.

PMID- 18079763
TI  - Further interpretation of the acute effect of nitrogen dioxide observed in
      Canadian time-series studies.
AB  - In this paper, the pooled NO2 association with nonaccidental mortality is
      examined across 10 cities in Canada in single- and two-pollutant time-series
      models. The results reaffirm that NO2 has the strongest association with
      mortality, particularly in the warm season. Although attributing such effects to
      NO2 cannot be ruled out, it is plausible that NO2 is acting as an indicator for
      some other exposure affecting the population. This could include PM2.5, as has
      been suggested from some personal exposure data, but it could also be indicating
      a more specific type of PM2.5, such as traffic-related particles, given that in
      cities the main source of NO2 is motor vehicle exhaust. NO2 could also be acting
      as a surrogate for other pollutant(s) originating from motor vehicles or high
      temperature combustion, such as volatile organic compounds (VOCs) or polycyclic
      aromatic hydrocarbons. Another possibility is other oxidized nitrogen species
      ("NO(z)") or photochemically produced pollutants that can co-vary with NO2,
      especially during urban stagnation events. Data to test these different
      possibilities across several Canadian cities are examined. The focus is on
      correlations in time or space between NO2 and other pollutants that are more
      strongly linked to vehicle emissions. The results support the hypothesis that NO2
      is a better indicator than PM2.5 of a range of other toxic pollutants. This
      includes VOCs, aldehydes, NO(z) and particle-bound organics in motor vehicle
      exhaust. Thus, overall, the strong effect of NO2 in Canadian cities could be a
      result of it being the best indicator, among the pollutants monitored, of fresh
      combustion (likely motor vehicles) as well as photochemically processed urban
      air.

PMID- 18079764
TI  - Characterization of PM2.5, gaseous pollutants, and meteorological interactions in
      the context of time-series health effects models.
AB  - Associations of particulate matter (PM) and ozone with morbidity and mortality
      have been reported in many recent observational epidemiology studies. These
      studies often considered other gaseous co-pollutants also as potential
      confounders, including nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon
      monoxide (CO). However, because each of these air pollutants can have different
      seasonal patterns and chemical interactions, the estimation and interpretation of
      each pollutant's individual risk estimates may not be straightforward. Multi
      collinearity among the air pollution and weather variables also leaves the
      possibility of confounding and over- or under-fitting of meteorological
      variables, thereby potentially influencing the health effect estimates for the
      various pollutants in differing ways. To investigate these issues, we examined
      the temporal relationships among air pollution and weather variables in the
      context of air pollution health effects models. We compiled daily data for PM
      less than 2.5 mum (PM2.5), ozone, NO2, SO2, CO, temperature, dew point, relative
      humidity, wind speed, and barometric pressure for New York City for the years
      1999-2002. We conducted several sets of analyses to characterize air pollution
      and weather data interactions, to assess different aspects of these data issues:
      (1) spatial/temporal variation of PM2.5 and gaseous pollutants measured at
      multiple monitors; (2) temporal relationships among air pollution and weather
      variables; and (3) extent and nature of multi-collinearity of air pollution and
      weather variables in the context of health effects models. The air pollution
      variables showed a varying extent of intercorrelations with each other and with
      weather variables, and these correlations also varied across seasons. For
      example, NO2 exhibited the strongest negative correlation with wind speed among
      the pollutants considered, while ozone's correlation with PM2.5 changed signs
      across the seasons (positive in summer and negative in winter). The extent of
      multi-collinearity problems also varied across pollutants and choice of health
      effects models commonly used in the literature. These results indicate that the
      health effects regression need to be run by season for some pollutants to provide
      the most meaningful results. We also find that model choice and interpretation
      needs to take into consideration the varying pollutant concurvities with the
      model co-variables in each pollutant's health effects model specification.
      Finally, we provide an example for analysis of associations between these air
      pollutants and asthma emergency department visits in New York City, which
      evaluate the relationship between the various pollutants' risk estimates and
      their respective concurvities, and discuss the limitations that these results
      imply about the interpretability of multi-pollutant health effects models.

PMID- 18079766
TI  - On the interpretation of epidemiological studies of ambient air pollution.
AB  - Studies of the effects of ambient air pollution on human health are complicated
      by the fact that individuals are exposed to a complex mixture of toxic and non
      toxic substances that vary in their make-up in space and in time. It is
      impossible using standard epidemiological designs to uniquely identify any
      individual component of air pollution as a causal agent of a health effect
      because of simultaneous exposure to all or a subset of ambient pollutants.
      Nevertheless, associations observed for a particular pollutant can be interpreted
      as a marker of toxicity of the mixture, and regulatory action on judiciously
      selected pollutants can benefit health, as such actions can modify the complex
      mixture. This paper argues that we may be able to further our understanding of
      the effects of air pollution on human health by investigating whether particular
      mixtures are more toxic through (1) conducting and reporting results for all
      measured components; (2) possibly characterizing the complex mixture by
      developing synoptic categorizations of daily air pollution, through cluster or
      latent profile analysis; (3) a careful analysis of differences in the mixtures
      between locations; and (4) toxicological studies and controlled studies on humans
      that make use of factorial designs for various components of the air pollution
      mixture.

PMID- 18079765
TI  - Health effects of air pollution observed in cohort studies in Europe.
AB  - In recent years, several studies in Europe have associated within-city contrasts
      in air pollution with various health end points including mortality in cohort
      studies of adults, and respiratory morbidity in cross-sectional and cohort
      studies of children. Many of these studies have used NO2 contrasts as the primary
      exposure variable, which raises the issue of whether such associations are
      uniquely found for NO2 per se, or whether NO2 acts as a surrogate for a complex
      mixture of combustion pollutants primarily derived from vehicular traffic.
      Exposure assessment in these studies has been based on dispersion modelling, on
      data from routine monitoring networks, on stochastic models developed from
      dedicated spatially resolved monitoring, or some combination of these. The
      results of a number of recent European studies are discussed.

PMID- 18079767
TI  - Viewpoint: using gene-environment interactions to dissect the effects of complex
      mixtures.
AB  - Teasing out the health effects of constituents of complex mixtures poses
      formidable statistical challenges owing to the problem of multicollinearity.
      While statistical devices such as regression on principal components, model
      selection, and model averaging offer some approaches to this problem,
      incorporation of external information is likely to be more helpful. I explore a
      general hierarchical modeling framework that would allow such information as
      sources, genetic interactions, and toxicology to be included in the higher levels
      of the model.

PMID- 18079769
TI  - Panel discussion review: session two--interpretation of observed associations
      between multiple ambient air pollutants and health effects in epidemiologic
      analyses.
AB  - Air pollution epidemiologic research has often utilized ambient air
      concentrations measured from centrally located monitors as a surrogate measure of
      exposure to these pollutants. Associations between these ambient concentrations
      and health outcomes such as lung function, hospital admissions, and mortality
      have been examined in short- and long-term cohort studies as well as in time
      series and case-crossover studies. The issues related to interpreting the
      observed associations of ambient air pollutants with health outcomes were
      discussed at the US EPA sponsored workshop on December 13 and 14, 2006 in Chapel
      Hill, North Carolina, USA. The second session of this workshop focused on the
      following topics: (1) statistical methodology and study designs that may improve
      understanding of multipollutant health effects; (2) ambient concentrations as
      surrogate measures of pollutant mixtures; and (3) source-focused epidemiologic
      research. New methodology and approaches to better distinguish the effects of
      individual pollutants include multicity hierarchical modeling and the use of case
      crossover analysis to control for copollutants. An alternative approach is to
      examine the mixture as a whole using principal component analysis. Another
      important consideration is to what extent the observed health associations are
      attributable to individual pollutants, which are often from common sources and
      are correlated, versus the pollutant mixtures that the pollutants are
      representing. For example, several ambient air concentrations, such as
      particulate matter mass, nitrogen dioxide, and carbon monoxide, may be serving as
      surrogate measures of motor vehicle exhaust. Source apportionment analysis is one
      method that may allow further advancement in understanding the source components
      that contribute to multipollutant health effects.

PMID- 18079768
TI  - Panel discussion review: session 1--exposure assessment and related errors in air
      pollution epidemiologic studies.
AB  - Examining the validity of exposure metrics used in air pollution epidemiologic
      models has been a key focus of recent exposure assessment studies. The objective
      of this work has been, largely, to determine what a given exposure metric
      represents and to quantify and reduce any potential errors resulting from using
      these metrics in lieu of true exposure measurements. The current manuscript
      summarizes the presentations of the co-authors from a recent EPA workshop, held
      in December 2006, dealing with the role and contributions of exposure assessment
      in addressing these issues. Results are presented from US and Canadian exposure
      and pollutant measurement studies as well as theoretical simulations to
      investigate what both particulate and gaseous pollutant concentrations represent
      and the potential errors resulting from their use in air pollution epidemiologic
      studies. Quantifying the association between ambient pollutant concentrations and
      corresponding personal exposures has led to the concept of defining attenuation
      factors, or alpha. Specifically, characterizing pollutant-specific estimates for
      alpha was shown to be useful in developing regression calibration methods
      involving PM epidemiologic risk estimates. For some gaseous pollutants such as
      NO2 and SO2, the associations between ambient concentrations and personal
      exposures were shown to be complex and still poorly understood. Results from
      recent panel studies suggest that ambient NO2 measurements may, in some
      locations, be serving as surrogates to traffic pollutants, including traffic
      related PM2.5, hopanes, steranes, and oxidized nitrogen compounds (rather than
      NO2).

PMID- 18079770
TI  - Panel discussion review: session three--issues involved in interpretation of
      epidemiologic analyses--statistical modeling.
AB  - The Clean Air Act mandates that the US Environmental Protection Agency (EPA)
      develop National Ambient Air Quality Standards for criteria air pollutants and
      conduct periodic reviews of the standards based on new scientific evidence. In
      recent reviews, evidence from epidemiologic studies has played a key role.
      Epidemiologic studies often provide evidence for effects of several air
      pollutants. Determining whether there are independent effects of the separate
      pollutants is a challenge. Among the many issues confronting the interpretation
      of epidemiologic studies of multi-pollutant exposures and health effects are
      those specifically related to statistical modeling. The EPA convened a workshop
      on 13 and 14 December 2006 in Chapel Hill, North Carolina, USA, to discuss these
      and other issues; Session Three of the workshop was devoted specifically to
      statistical modeling. Prominent statistical modeling issues in epidemiologic
      studies of air pollution include (1) measurement error across the co-pollutants;
      (2) correlation and multi-collinearity among the co-pollutants; (3) the timing of
      the concentration-response function; (4) confounding; and (5) spatial analyses.

PMID- 18079771
TI  - Panel discussion review: session four--assessing biological plausibility of
      epidemiological findings in air pollution research.
AB  - In December 2006, the U.S. Environmental Protection Agency (EPA) sponsored a 2
      day workshop on "Interpretation of Epidemiologic Studies of Multipollutant
      Exposure and Health Effects" in Chapel Hill, NC. The final session at this
      workshop was devoted to assessing the biological plausibility of epidemiological
      findings with regard to criteria air pollutants. The presentations and the panel
      contributions of this last session primarily focused on controlled exposure
      studies and led to wide-ranging discussions, some of which were provocative. The
      panel summary provides some guidance to future evaluations of the biological
      plausibility of the epidemiological reports on criteria pollutants and is
      intended to stimulate thinking, without drawing any definitive conclusions. This
      paper does not approach, nor was it intended to approach, the more formal
      analytical approach such as that used in EPA's development of its Science
      Assessment Document for the criteria pollutants.

PMID- 18079772
TI  - Random surfaces that suppress single scattering.
AB  - We present a method for numerically generating a one-dimensional random surface,
      defined by the equation x(3)=zeta(x(1)), that suppresses single-scattering
      processes in the scattering of light from the surface within a specified range of
      scattering angles. Rigorous numerical calculations of the scattering of light
      from surfaces generated by this approach show that the single-scattering
      contribution to the mean scattered intensity is indeed suppressed within that
      range of angles.

PMID- 18079773
TI  - Interferometry of hyper-Rayleigh scattering by inhomogeneous thin films.
AB  - The use of specific symmetry properties of optical second-harmonic generation
      (the s, s-exclusion rule) has allowed us to observe high-contrast hyper-Rayleigh
      interference patterns in completely diffuse light, an effect that has no analog
      in the case of linear (Rayleigh) scattering.

PMID- 18079774
TI  - Long-period fiber gratings based on periodic microbends.
AB  - We demonstrate a new type of high-performance long-period fiber grating based on
      arc-induced periodic microbends. The fabrication method is simple and does not
      require special fibers. Flexibility in controlling the filter parameters makes it
      possible to produce arbitrary filter profiles by use of a simple apodization
      technique, which is difficult to do with conventional long-period gratings.

PMID- 18079775
TI  - Bragg gratings in defect-free germanium-doped optical fibers.
AB  - Bragg gratings have been written in germanium-doped optical fibers that have been
      treated to remove the UV absorption bands associated with oxygen-deficient
      defects. When one is using high-intensity 193-nm light from an ArF excimer laser
      to fabricate the gratings, the refractive index increases and the grating
      transmission spectra are similar to those obtained in standard (untreated) fiber.

PMID- 18079776
TI  - Holographic recording and retrieval of polarized light by use of polyester
      containing cyanoazobenzene units in the side chain.
AB  - We examined the holographic recording properties of polyester containing
      cyanoazobenzene units in the side chain. It was revealed that, when a linearly
      polarized object beam with an arbitrary polarization direction was recorded, the
      retrieved beam had the same polarization state as that of the object beam, with a
      constant diffraction efficiency of 0.1. Moreover, two object beams with mutually
      orthogonal linear polarization could be recorded and retrieved separately from
      the same area. This is, to our knowledge, the first example of holographic
      polarization multiplexing. The retrieved images were found to resolve details of
      ~40line pairs/mm and a 40-mum -pitched checkerboard pattern. The resolution of
      the system is limited by the CCD cameras that are used. Polarization encoding to
      increase the storage capacity and (or) the signal-to-noise ratio of holographic
      data recording is also discussed.

PMID- 18079777
TI  - Robust one-beam interferometer with phase-delay control.
AB  - A robust one-beam interferometer with external phase-delay control is described.
      The device resembles a Mach-Zehnder interferometer in which the two arms are
      together in one collimated beam. However, the proposed device is not an amplitude
      division interferometer but a wave-front division one. The phase-delay control
      occurs at the interferometer output with the help of two polarizing beam
      splitters, a quarter-wave plate, a Faraday rotator, and a polarizer. An
      additional phase delay is introduced by application of an electrical current to
      the Faraday rotator or by rotation of the polarizer (the latter is of topological
      origin), which permits the use of techniques of phase-stepping interferometry.

PMID- 18079778
TI  - Statistical properties of low-frequency fluctuations during single-mode operation
      in distributed-feedback lasers: experiments and modeling.
AB  - Extensive experimental and numerical investigations of feedback-induced
      instabilities in single-mode distributed-feedback lasers are presented that
      confirm the basic assumptions of the Lang-Kobayashi model. We give experimental
      evidence of the occurrence of low-frequency fluctuation (LFF), alternation
      between LFF and stable emission, and coherence collapse during single-mode
      operation of the laser. We have obtained quantitative agreement between modeling
      and experiment in long-time statistical investigations of the time intervals
      between subsequent LFF dropouts. In particular, we show that even the dependence
      of the dynamics on the injection current, which results in a scaling law, is
      quantitatively identical in modeling and experiment.

PMID- 18079779
TI  - Microcavity lasing of optically excited cadmium sulfide thin films at room
      temperature.
AB  - We report what is believed to be the first observation of lasing of an optically
      pumped thin CdS film formed by laser ablation on glass. Laser action is observed
      at room temperature, and the emission peak is at 501 nm. X-ray diffraction shows
      that the polycrystalline films are of wurtzite structure and have (002) preferred
      orientation. Fabry-Perot laser modes are spaced 16 nm apart, indicating a cavity
      length of 2.9mum . The cavity is formed by consistently self-formed microcavities
      within the hexagonal lattice.

PMID- 18079780
TI  - High-power diode-pumped passively mode-locked Yb:YAG lasers.
AB  - We obtained 74-kW peak power and 3.5-W average output power in 1-ps pulses from a
      diode-pumped Yb:YAG laser at 1030 nm that was passively mode locked with a
      semiconductor saturable-absorber mirror. Another laser produced 57-kW peak power
      and as much as 8.1-W average output power in 2.2-ps pulses, split into two nearly
      diffraction-limited beams (M(2)<1.2) . To our knowledge, these are by far the
      highest reported peak and average output powers from a diode-pumped mode-locked
      laser in this pulse-duration regime.

PMID- 18079781
TI  - Diode-pumped 1-W Er-doped fluoride glass M-profile fiber laser emitting at 2.8
      mum.
AB  - We report a novel short-length diode-pumped cw fiber laser with high output power
      at a wavelength of 2.8mum . The system combines continuous-wave diode pumping at
      970 nm, a high doping concentration (5-mol. % ErF(3)) of the active fiber, and an
      annular geometry of the laser medium, an M-profile fiber. Output powers in excess
      of 1 W with a slope efficiency of 25% were obtained.

PMID- 18079782
TI  - Fourfold output power enhancement and threshold reduction through thermal effects
      in an Er(3+)/Yb(3+)-codoped optical fiber laser excited at 1.064 mum.
AB  - Thermally induced output power enhancement and threshold reduction in an
      Er(3+)/Yb(3+) -codoped optical fiber laser at 1.54mum pumped by 1.064-mu;m cw
      radiation is demonstrated. Steady fourfold output power increase and threshold
      decrease were achieved by heating of the Yb(3+) -sensitized Er(3+) -doped fiber
      laser medium in the temperature range 23-150 degrees C degrees . The laser
      efficiency thermal behavior is assigned to the temperature-dependent effective
      absorption cross section of the ytterbium sensitizer through the so-called
      multiphonon-assisted anti-Stokes excitation process.

PMID- 18079783
TI  - Method for measuring the mean time of flight spent by photons inside a volume
      element of a highly diffusing medium.
AB  - A method of measuring the mean time of flight, ?t(i)? , spent by photons inside a
      generic volume element of a highly diffusing medium is presented. The method
      comes from a general property of the radiative transfer equation and is based on
      relative measurements of cw attenuation that correspond to small variations of
      the absorption coefficient inside the volume element. By use of a liquid phantom
      and small gels with known optical properties it was possible to measure ?t(i)?
      with good accuracy, even when it was only a few picoseconds long. The results
      were in good agreement with Monte Carlo results.

PMID- 18079784
TI  - Continuous-wave quasi-phase-matched generation of 60 mW at 465 nm by single-pass
      frequency doubling of a laser diode in backswitch-poled lithium niobate.
AB  - We report continuous-wave single-pass second-harmonic generation (SHG) in 4-mum 
      period 0.5-mm-thick backswitch-poled lithium niobate. Pump sources at 920-930 nm
      include both Ti:sapphire and diode-oscillator-amplifier lasers. SHG of a
      Ti:sapphire laser at 6.1%/W efficiency, producing 61 mW of power at 460 nm, is
      demonstrated in 50-mm-long periodically poled lithium niobate samples with a
      nonlinear coefficient d(eff) approximately 9pm/V, and 60 mW at 465 nm and 2.8%/W
      efficiency is obtained by SHG of a laser-diode source.

PMID- 18079785
TI  - Polarization switching as a result of cascading of two simultaneously phase
      matched quadratic processes.
AB  - A method of intensity-dependent polarization switching is proposed. The effect is
      based on simultaneous action of two phase-matched second-order processes in a
      quadratic medium. Using analytical and numerical techniques, we demonstrate that
      a single linearly polarized fundamental wave, when it is propagating in such a
      medium, can efficiently generate a new fundamental wave of orthogonal
      polarization. The polarization switching is explained by an effective four-wave
      mixing process that is performed through second-order cascading.

PMID- 18079786
TI  - Second-harmonic generation in He+-implanted gadolinium calcium oxoborate planar
      waveguides.
AB  - What is believed to be the first investigation of second-harmonic generation
      (SHG) in Ca(4)GdO (BO(3))(3) waveguides is reported. A planar waveguide was
      formed by 2-MeV-helium implantation. We cut the sample to achieve type I
      noncritical phase matching of an 823-nm fundamental wave for fundamental light
      propagating along the y axis and polarized along the z crystallophysic axis of
      the crystal. SHG was achieved with a relatively low pumping power of a cw
      Ti:sapphire laser. The results indicate that the nonlinearity of the material
      remains in the guiding region after ion implantation.

PMID- 18079787
TI  - Nonvolatile holographic storage in iron-doped lithium tantalate with continuous
      wave laser light.
AB  - Holograms have been recorded in congruent LiTaO(3):Fe with continuous-wave laser
      light by use of a two-step process. Blue gating light (lambda=488 nm) sensitizes
      the crystals for holographic recording with red light (lambda=660 nm) of a diode
      laser. Refractive-index changes of as much as 1.0x10(-5) are achieved for
      intensities of the red light of 1 W/cm(2) . The saturation values are
      proportional to the intensity of the writing light. Nondestructive readout with
      red light is possible, and the holograms remain erasable for blue light.

PMID- 18079788
TI  - Detection of ultrafast phenomena by use of a modified Sagnac interferometer.
AB  - We describe a time-division interferometer based on the Sagnac geometry for
      monitoring ultrafast changes in the real and the imaginary components of the
      refractive index as well as phase changes that are due to surface displacement.
      Particular advantages of this interferometer are its simple common-path design
      and operation at normal incidence with a microscope objective for both pumping
      and probing. Operation is demonstrated by detection of temperature changes and
      coherent phonon generation in a gold film.

PMID- 18079789
TI  - High-energy conversion efficiency of transient stimulated Raman scattering in
      methane pumped by the fundamental of a femtosecond Ti:sapphire laser.
AB  - We studied stimulated Raman scattering in pressurized methane in the highly
      transient regime pumped by 140-fs 0.7-mJ pulses from a Ti:sapphire (Ti:S) laser
      tuned at 750 nm. Energy-conversion efficiency of the first Stokes of more than
      15% was achieved, with no strong sign of saturation with as much as 40 atm
      (1atm=760Torr) of Raman gas pressure. To our knowledge, this is the highest
      conversion efficiency of transient stimulated Raman scattering generated directly
      from the fundamental of a Ti:S laser.

PMID- 18079790
TI  - Infrared photosensitivity in silica glasses exposed to femtosecond laser pulses.
AB  - We investigate the use of infrared femtosecond laser pulses to induce highly
      localized refractive-index changes in fused-silica glasses. We characterize the
      magnitude of the change as a function of exposure and measure index changes as
      large as 3x10(-3) and 5x10(-3) in pure fused silica and boron-doped silica,
      respectively. The potential of this technique for writing three-dimensional
      photonic structures in bulk glasses is demonstrated by the fabrication of a Y
      coupler within a sample of pure fused silica.

PMID- 18079791
TI  - Characterization of sub-6-fs optical pulses with spectral phase interferometry
      for direct electric-field reconstruction.
AB  - We demonstrate spectral phase interferometry for direct electric-field
      reconstruction (SPIDER) as a novel method to characterize sub-6-fs pulses with
      nanojoule pulse energy. SPIDER reconstructs pulse phase and amplitude from a
      measurement of only two optical spectra by use of a fast noniterative algorithm.
      SPIDER is well suited to the measurement of ultrabroadband pulses because it is
      quite insensitive to crystal phase-matching bandwidth and to unknown detector
      spectral responsivity. Moreover, it combines highly accurate pulse-shape
      measurement with the potential for online laser system diagnostics at video
      refresh rates.

PMID- 18079792
TI  - Effects of lateral load and external twist on polarization-mode dispersion of
      spun and unspun fibers.
AB  - Using the coupled-mode theory, we have developed a theoretical model to analyze
      the effects of lateral load and external twist on polarization-mode dispersion
      (PMD) of spun and unspun fibers. Modeling results show that spun and unspun
      fibers have very different PMD responses to lateral load and external twist.
      Experimental results show good agreement with the theory.

PMID- 18079793
TI  - Dual on-fiber thin-film heaters for fiber gratings with independently adjustable
      chirp and wavelength.
AB  - Dual, independently addressable thin-film resistive heaters fabricated in a
      multilayer geometry on the surface of an optical fiber provide a new, flexible
      means for thermally tuning the properties of intracore gratings. In particular,
      control of the current that is applied to each of these heaters permits the chirp
      and the central wavelength of the grating to be adjusted independently. The
      designs and simple fabrication procedures for these types of device, the
      important physics of heat flow in them, and a tunable add-drop filter that
      demonstrates essential aspects of their operation are described.

PMID- 18079794
TI  - All-incoherent dispersion-compensated optical correlator.
AB  - We report on a simple, spatially incoherent, wavelength-independent imaging
      system that, in contrast to the conventional case, exhibits a dispersion
      compensated point-spread function. Our hybrid (diffractive-refractive) three-lens
      imaging configuration thus acts as an all-incoherent dispersion-compensated
      optical irradiance correlator. So the optical arrangement is well adapted to
      processing color information (both spatially and temporally incoherent) under
      natural illumination.

PMID- 18079795
TI  - Analysis of photoinduced stress distribution in fiber Bragg gratings.
AB  - We discuss the analytical expressions that describe the displacement field
      resulting from the inscription of a Bragg grating in a Ge-doped optical fiber.
      The equations stem from a phenomenological approach and allow calculation of the
      induced stresses. Our model provides an efficient tool to analyze the effects of
      radiation-induced density variations on the properties of fiber Bragg gratings.

PMID- 18079796
TI  - Lens-free in-line optical isolators.
AB  - We constructed a lens-free in-line optical isolator by embedding an isolator chip
      in a thermally expanded core (TEC) fiber without complicated optical alignment.
      The chip consists of two pairs of rutile wedges and garnet plates. We fabricated
      the TEC fibers by heating a single-mode fiber with a 200-mum outer diameter; low
      loss and a spot diameter as large as 49 mum were successfully obtained. The
      fabricated isolator has excellent optical properties, an insertion loss of 0.45
      dB, and an isolation of more than 50 dB at a 1.55-mum wavelength, which confirms
      the usefulness of the integration techniques.

PMID- 18079797
TI  - Pixel size limit in holographic memories.
AB  - The bandwidth of holographic recording in LiNbO(3) (Fe doped) in the 90 degrees
      geometry is studied theoretically and experimentally. The wide holographic
      bandwidth of LiNbO(3) makes it possible to record submicrometer pixels and
      reconstruct them by phase conjugation in a holographic memory system. This
      approach reduces the system cost and increases the system storage density. We
      demonstrate the recording and the phase-conjugate reconstruction of various pixel
      sizes down to 1 mumx1 mum . The signal-noise ratio and the bit-error rate are
      examined.

PMID- 18079798
TI  - Pressure tuning of thermal lensing for high-power scaling.
AB  - A new concept is introduced whereby thermal stresses generated through the
      pumping process are canceled by an applied force. By use of a Nd:YVO(4) disk
      laser as a model system, significant reduction of thermal lensing and deformation
      is demonstrated as a function of applied pressure, and the output power (19 W
      TEM(00)) is limited only by the available pump power.

PMID- 18079799
TI  - Nonlinear dynamics of self-pulsating laser diodes under external drive.
AB  - A self-pulsating laser diode under external drive shows the nonlinear dynamical
      effects of two competing frequencies. One can establish a route to chaos by
      increasing the modulation current. However, when the modulation frequency is
      varied, the chaotic state is suddenly destroyed at the harmonic frequencies of
      the self-pulsating frequency. This approach therefore offers a simple chaotic
      light source for possible optical chaotic communication.

PMID- 18079800
TI  - Photoinduced orientation of azo dye in various polymer matrices.
AB  - Photoinduced dichroism in various polymers containing the same azo dye has been
      studied. "Angular hole burning" and molecular reorientation have been identified
      by analysis of dichroism dynamics at various probe wavelengths. The glass
      transition temperature T(g) is of major relevance for the reorientation of
      optically active molecules. For low T(g) (below ambient temperature) thermal
      diffusion impedes anisotropy buildup. For higher T(g) the angular distribution
      induced by the polarized pump beam is frozen. We propose a simple model based on
      diffusion rates in trans and cis molecules.

PMID- 18079801
TI  - High photosensitivity and nanometer-scale phase separation in GeO(2)-SiO(2) glass
      thin films.
AB  - Amorphous xGeO(2)-(1-x)SiO(2) thin films exhibit large negative index changes (4
      8%) in the high GeO(2) region (x>~0.25) on irradiation with ArF laser pulses. The
      sign of the index change is opposite the low GeO(2) region X<0.25, and the
      magnitude of the index change is larger by an order of magnitude than that
      reported so far. Cross-sectional transmission electron microscope observation has
      revealed that nanometer-scale phase separation is induced in these highly
      photosensitive glasses by irradiation with ArF excimer laser light pulses or
      electron beams. This is a first finding of microphase separation in SiO(2)-GeO(2)
      glasses by irradiation and provides an essential constraint on the modeling of
      photonic effects induced by irradiation in these glasses.

PMID- 18079802
TI  - Improved sensitivity in blue-membrane bacteriorhodopsin films.
AB  - We show that D85N/V49A, a mutant bacteriorhodopsin in which two residues,
      aspartate (D) at position 85 and valine (V) at position 49, have been replaced
      with asparagine (N) and alanine (A), respectively, has significantly improved
      optical properties compared with other forms of blue-membrane Bacteriorhodopsin.
      Absorption studies of the mutant in gels show that it forms the P(490) state at
      light levels that are comparable with M-state formation in wild-type films.
      Theoretical calculations based on Kramers-Kronig transformation of light-induced
      absorption data predict that the refractive index is three times larger than that
      of mutant D85N. Holographic measurements performed on gelatin-based films confirm
      that the sensitivity is improved by a factor of 50 over that of D85N.

PMID- 18079803
TI  - Real-time in vivo imaging of human gastrointestinal ultrastructure by use of
      endoscopic optical coherence tomography with a novel efficient interferometer
      design.
AB  - We report on the design and initial clinical experience with a real-time
      endoscopic optical coherence tomography (EOCT) imaging system. The EOCT unit
      includes a high-speed optical coherence tomography interferometer, endoscope
      compatible catheter probes, and real-time data capture and display hardware and
      software. Several technological innovations are introduced that improve EOCT
      efficiency and performance. In initial clinical studies using the EOCT system,
      the esophagus, stomach, duodenum, ileum, colon, and rectum of patients with
      normal endoscopic findings were examined. In these initial investigations, EOCT
      imaging clearly delineated the substructure of the mucosa and submucosa in
      several gastrointestinal organs; microscopic structures such as glands, blood
      vessels, pits, villi, and crypts were also observed.

PMID- 18079804
TI  - Dispersive-scan measurement of the fast component of the third-order nonlinearity
      of bulk materials and waveguides.
AB  - A new, simple method to measure the nonlinear refraction and absorption of bulk
      material and waveguides is proposed. The method relies on the evolution of the
      intensity and width of femtosecond-pulse spectra, owing to self-phase modulation,
      as a function of variable chirp and stretching introduced at the input.

PMID- 18079805
TI  - Optical nonlinearity and structural phase-transition observation of organic dye
      doped polymer silica hybrid material.
AB  - The optical nonlinearity of organic dye-doped poly(methyl methacrylate) (PMMA)
      silica-gel hybrid material was investigated by second-harmonic-generation
      measurement. We found that incorporation of in situ polymerized solgel precursors
      into the organic dye-doped PMMA significantly improved the nonlinear optical
      stability of the system. However, improvement of thermal stability occurred only
      when a sufficient amount of silica gel was incorporated. A structural phase
      transition from pure polymer to a hybrid system was found near a 10-mol.% silica
      gel concentration. The optimum polymer/tetraethoxysilane molar ratio is 2:1 to
      1:1.

PMID- 18079806
TI  - Near-field optical study of photorefractive surface waves in BaTiO(3).
AB  - Near-field optical microscopy has been used to study photorefractive surface
      waves in BaTiO(3). The field distribution of the photorefractive surface wave
      near the crystal-air interface has been measured and compared with theory.
      Experimental data indicate that a micrometer-wide transition layer with
      dielectric and photorefractive properties that are different from the properties
      of the bulk BaTiO(3) exists near the interface.

PMID- 18079807
TI  - Heterodyne measurement of Wigner distributions for classical optical fields.
AB  - We demonstrate a two-window heterodyne method for measuring the x-p cross
      correlation, ??(*)(x)? (p)?, of an optical field ? for transverse position x and
      transverse momentum p. This scheme permits independent control of the x and p
      resolution. A simple linear transform of the x-p correlation function yields the
      Wigner phase-space distribution. This technique is useful for both coherent and
      low-coherence light sources and may permit new biological imaging techniques
      based on transverse coherence measurement with time gating. We point out an
      interesting analogy between x-p correlation measurements for classical-wave and
      quantum fields.

PMID- 18079808
TI  - Femtosecond cubic optical nonlinearity of thin nickel films.
AB  - Transient pump-probe measurements of circular anisotropy in nickel films induced
      by 38-fs optical pulses show an instantaneous response that is related to the
      optical orientation of the spins of free electrons. Measurements in a sample of
      variable thickness, performed in both transmission and reflection, revealed that
      the surface significantly influences the degenerate cubic optical nonlinearity of
      the nickel films to a depth of approximately 4-5 nm into the bulk.

PMID- 18079809
TI  - Improved robustness of target location in nonhomogeneous backgrounds by use of
      the maximum-likelihood ratio test location algorithm.
AB  - We address the problem of localizing small targets with random gray levels that
      appear in random background clutter. We consider the recently proposed maximum
      likelihood ratio test (MLRT) algorithm, which scans the observed scene with an
      estimation window in which the local statistics are estimated. In the presence of
      a spatially homogeneous background, we show that if the estimation window is a
      few times larger than the target itself, the MLRT is quasi-equivalent to the
      optimal maximum-likelihood (ML) algorithm, which uses the whole scene for
      estimating the background statistics. The MLRT thus constitutes an efficient
      alternative to the ML algorithm and is more robust in dealing with spatially
      nonhomogeneous clutter since it utilizes a small estimation window.

PMID- 18079810
TI  - Variable-time-delay optical coherent transient signal processing.
AB  - A technique is proposed and experimentally demonstrated that achieves
      simultaneous optical pattern waveform storage and programmable time delay for
      continuous real-time signal processing by use of optical coherent transient
      technology. We achieve variable-time-delay and broadband signal processing by
      frequency shifting of two chirped programming pulses, the chirp rate of one being
      twice that of the other, without using brief reference pulses and without
      changing the timing of the programming sequence. We demonstrate the technique
      experimentally in Tm(3+): YAG at 5 K for 40-MHz chirps by performing temporal
      signal convolution with true-time delays that vary over a 250-ns range.

PMID- 18079811
TI  - Generation and characterization of 0.6-THz polarization domain-wall trains in an
      ultralow-birefringence spun fiber.
AB  - Polarization domain-wall (PDW) trains have been generated at a repetition rate of
      0.6 THz in an ultralow-birefringence spun optical fiber and measured by use of an
      adapted frequency-resolved optical gating technique. Characterization of the
      intensity and the phase of the PDW train shows complete switching between
      adjacent domains of counterrotating circular polarizations and directly confirms
      predictions based on numerical simulations of the incoherently coupled nonlinear
      Schrodinger equations.

PMID- 18079812
TI  - Observation of chirped soliton dynamics at lambda = 1.55 microm in a single-mode
      optical fiber with frequency-resolved optical gating.
AB  - We present an experimental observation of the dynamics of an initially chirped
      optical soliton at 1.55microm that is propagating through a single-mode optical
      fiber, using frequency-resolved optical gating (FROG). FROG permits observation
      of both the amplitude and the phase profiles of ultrashort pulses, providing
      complete information on the pulse evolution. The features that are detected,
      which include what is believed to be the first experimental observation of phase
      slips, are in quantitative agreement with numerical simulations that employ the
      nonlinear Schrodinger equation.

PMID- 18079813
TI  - Nonlinearity in holey optical fibers: measurement and future opportunities.
AB  - Holey fibers combine two-dimensional microstructuring with one-dimensional
      longitudinal propagation, resulting in fibers with tailorable dispersive and
      nonlinear properties. We measure the effective nonlinearity of a typical holey
      fiber. The small effective area that is possible in this type of fiber
      significantly enhances its effective nonlinearity relative to standard fiber.

PMID- 18079814
TI  - Pulsed top-hat beam thermal-lens measurement for ultraviolet dielectric coatings.
AB  - A mode-mismatched surface thermal-lens technique with pulsed top-hat beam
      excitation and a near-field detection scheme are developed to measure in situ the
      thermoelastic response of ultraviolet dielectric coatings to excimer-laser (193-
      or 248-nm) irradiation. The thermal-lens technique is demonstrated to be not only
      convenient for accurate determination of the laser-induced damage threshold
      (LIDT) but also sensitive to measurement of the thermoelastic response of
      dielectric coatings irradiated with fluence far below the LIDT, and hence is
      shown to be appropriate for time-resolved predamage investigation. A minimum
      detectable surface displacement of approximately 0.002 nm is achieved with a
      simple experimental configuration. Nonlinear absorption as well as the nonlinear
      effect in laser conditioning of a LaF(3)/MgF (2) highly reflective dielectric
      coating are observed for what is believed to be the first time.

PMID- 18079815
TI  - Excimer-laser-induced densification in binary silica glasses.
AB  - We report that the rate of excimer-laser-induced densification is a strong
      function of composition in the binary metal-oxide-silica system. The pulsed
      excimer-laser-induced densification rate is shown to increase with metal-oxide
      content. A good correlation was found between the densification rate and the
      relative softness of the glass, as indicated by the annealing temperature. The
      densification rate for all the glasses was also found to be a strong function of
      the excimer-laser wavelength in the order 157nm>193nm >248nm .

PMID- 18079816
TI  - Crystallization of GeO(2)-SiO(2) glass by poling with ArF-laser excitation.
AB  - We report on crystallization of 15.7GeO(2) 84.3SiO(2) (in mol.%) glass by poling
      with ArF-laser excitation. The UV intensity was 100(mJ/cm (2))/pulse , and the
      number of shots was 10(4) . The crystallites that were observed in the glass were
      approximately 15-20microm in diameter. The crystallization feature was dependent
      on the poling electric field, showing a threshold field of ~0.5x10(5)V/cm ,
      beyond which crystallization occurred.

PMID- 18079817
TI  - Two-photon optical-beam-induced current imaging of indium gallium nitride blue
      light-emitting diodes.
AB  - Epilayers of packaged indium gallium nitride light-emitting diodes (LED's) are
      characterized by optical-beam-induced current (OBIC) and photoluminescence laser
      scanning microscopy through two-photon excitation. Light scattering and
      absorption in the packaging material and the p-doped top layer of the LED's are
      greatly reduced as a result of employing a longer excitation wavelength, with
      energy that is less than the bandgap of the top p layer. Compared with single
      photon OBIC, two-photon OBIC imaging not only exhibits superior image quality but
      also reveals more clearly the characteristics of the epilayers that are being
      focused on.

PMID- 18079818
TI  - Observation of quadratic spatial solitons in periodically poled lithium niobate.
AB  - We report what are to our knowledge the first observation and characterization of
      quadratic spatial solitons in periodically poled lithium niobate (PPLN). Using a
      Nd:YAG (1064-nm) source, we observed self-trapped solitary-wave propagation over
      more than six diffraction lengths as a result of the cascaded quadratic nonlinear
      process. Low-threshold operation (5-kW peak power) was measured for the quasi
      phase-matched PPLN structure designed for frequency doubling.

PMID- 18079819
TI  - Engineering competing nonlinearities.
AB  - Weak modulation of a quasi-phase-matching (QPM) grating opens possibilities for
      engineering both the average quadratic nonlinearity and the incoherent average
      cubic nonlinearity induced by QPM. The relative strength of the average quadratic
      and effective (intrinsic plus induced) cubic nonlinearity is studied for LiNbO(3)
      . We show how the induced average cubic nonlinearity can be engineered to
      dominate the intrinsic material cubic nonlinearity and how doing so will allow
      the intensity at which the quadratic and cubic nonlinearities balance and thus
      compete to be decreased to a few gigawatts per square centimeter.

PMID- 18079820
TI  - Accessing the optical nonlinearity of metals with metal- dielectric photonic
      bandgap structures.
AB  - Metals typically have very large nonlinear susceptibilities (~10(6) times larger
      than those of typical dielectrics), but because they are nearly opaque their
      nonlinear properties are effectively inaccessible. We demonstrate numerically
      that a multilayer metal-dielectric structure in which the metal is the dominant
      nonlinear [chi((3))] material can have much larger intensity-dependent changes in
      the complex amplitude of the transmitted beam than a bulk sample containing the
      same thickness of metal. For 80 nm of copper the magnitude of the nonlinear phase
      shift is predicted to be as much as 40 times larger for the layered copper-silica
      sample, and the transmission is also greatly increased. The effective nonlinear
      refractive-index coefficient n(2) of this composite material can be as large as
      (3+6iota)x10(-9) cm (2)/W , which is among the largest values for known,
      reasonably transmissive materials.

PMID- 18079821
TI  - Low-temperature thermal fixing of holograms in photorefractive
      La(3)Ga(5)SiO(14):Pr(3+) crystal.
AB  - Thermal fixing in a La(3)Ga (5)SiO (14):Pr (3+) photorefractive crystal is
      demonstrated all the way down to room temperature. This, to our knowledge, is the
      first report of such an effect in any photorefractive material. From the
      temperature dependence of the process the activation energy of the carriers
      involved in the fixing process is measured to be E(A)=0.89 eV . Further, an
      effective photorefractive charge density of (1.4+/-0.2)x10(16) cm (-3) and Debye
      screening length of (6.8+/-0.7)x10(-6) cm is measured.

PMID- 18079822
TI  - Broadband antireflection gratings fabricated upon silicon substrates.
AB  - We fabricated a two-dimensional subwavelength structured (SWS) surface upon a
      crystal silicon substrate. The SWS surface was patterned by electron beam
      lithography and etched by an SF(6) fast atom beam. The SWS grating had a conical
      profile, the period was 150 nm, and the groove was approximately 350 nm deep. The
      reflectivity was examined at 2002500-nm wavelengths. At 400 nm the reflectivity
      decreased to 0.5% from the 54.7% of the silicon substrate. We also used HeNe
      laser light to examine the reflectivity as a function of the incident angle.

PMID- 18079823
TI  - Phase-dependent loss due to nonadiabatic ionization by sub-10-fs pulses.
AB  - For the first time to the author's knowledge, the effect of phase-dependent loss
      that can be used to stabilize the phase of a sub-10-fs laser pulse with respect
      to the envelope is shown. This loss is caused by the nonadiabatic response of an
      atom illuminated by a short pulse, which leads to the dependence of the tunneling
      ionization on the absolute phase of the pulse. The phase selectivity can be
      employed as a phase-dependent filter within the laser cavity with important
      applications in nonlinear optics in the single-cycle regime.

PMID- 18079824
TI  - Ultrawide tunable Er soliton fiber laser amplified in Yb-doped fiber.
AB  - A Raman-shifted and frequency-doubled high-power Er-fiber soliton laser for
      seeding an efficient high-power Yb fiber femtosecond amplifier is demonstrated.
      The Raman-shifted and frequency-doubled Er-soliton laser is tunable from 1.00 to
      1.070microm and produces bandwidth-limited 24-pJ pulses at a repetition rate of
      50 MHz with a FWHM pulse width of 170 fs at 1.040microm . The Yb(3+) amplifier
      has a slope efficiency of 52% and generates 3-ps linearly chirped pulses with an
      average power of 0.8 W at 1.05microm . After pulse compression, 74-fs bandwidth
      limited pulses with an average power of 0.4 W and a pulse energy of 8 nJ are
      generated.

PMID- 18079825
TI  - Propagation of ultrawideband short pulses of terahertz radiation through
      submillimeter-diameter circular waveguides.
AB  - We report experimental investigations in which quasi-optical methods were used to
      efficiently couple freely propagating, optoelectronically generated,
      subpicosecond pulses of terahertz (THz) radiation into submillimeter circular
      metal tubes (waveguides) and, consequently, to measure the transmitted pulses
      from these waveguides. We observe very dispersive low-loss propagation over the
      frequency band from 0.65 to 3.5 THz, with frequency-dependent group velocities
      nu(g) ranging from c/4 to c and phase velocities nu(p) from 4c to c , where
      nu(g)nu(p)=c(2) . The linearly polarized incoming THz pulses couple significantly
      only into the TE(11) , TM(11) , and TE(12) modes of the utilized 24- and 4-mm
      long stainless-steel tubes, with inside diameters of 240 and 280microm ,
      respectively.

PMID- 18079826
TI  - Time-interval analysis of laser-pulse-timing fluctuations.
AB  - A new technique has been proposed and demonstrated for measuring the pulse-timing
      fluctuations of mode-locked lasers at low Fourier frequencies. The time interval
      between the laser pulses is precisely measured by use of zero-dead-time counters
      referenced to a stable atomic oscillator. By combination of this method with the
      time-domain demodulation technique, the phase-noise power spectral density of a
      mode-locked Cr:LiSAF laser has been estimated for the 1-mHz-1-MHz Fourier
      frequency range, with a 240-dB dynamic range.

PMID- 18079827
TI  - Vector-based plane-wave spectrum method for the propagation of cylindrical
      electromagnetic fields.
AB  - We present a vector-based plane-wave spectrum (VPWS) method for efficient
      propagation of cylindrical electromagnetic fields. In comparison with
      electromagnetic propagation integrals, the VPWS method significantly reduces time
      of propagation. Numerical results that illustrate the utility of this method are
      presented.

PMID- 18079828
TI  - Optical trapping of nanoparticles and microparticles by a Gaussian standing wave.
AB  - The optical trapping of nanoparticles and microparticles by a Gaussian standing
      wave is experimentally demonstrated for the first time to the authors' knowledge.
      The standing wave is obtained under a microscope objective as a result of the
      interference of an incoming laser beam and a beam reflected on a microscope slide
      that has been coated with a system of reflective dielectric layers. Experimental
      results show that three-dimensional trapping of nanoparticles (100-nm polystyrene
      spheres) and one or more vertically aligned micro-objects (5-mum polystyrene
      spheres, yeast cells) can easily be achieved by use of even highly aberrated
      beams or objectives with low numerical apertures.

PMID- 18079829
TI  - Scattering from particles on surfaces: visibility factor and polydispersity.
AB  - We have developed an experimental method based on the visibility factor of light
      scattering minima to obtain size-polydispersity information from contaminants
      upon a flat substrate. We verify the method by using double-interaction-model
      calculations and use this technique to examine experimentally the radial
      variation of a micrometer-sized fiber and the size polydispersity of spherical
      particles upon a substrate.

PMID- 18079830
TI  - Pulse-overlapped dispersion-managed data transmission and intrachannel four-wave
      mixing.
AB  - We show that strong overlap of adjacent pulses in dispersion-managed return-to
      zero transmission reduces pulse-to-pulse interaction and timing jitter. The
      limiting factors for this pulse-overlapped transmission are the amplitude
      fluctuations and the ghost pulse generation induced by four-wave mixing between
      spectral components within a single channel.

PMID- 18079831
TI  - Novel designs for sampled grating-based multiplexers demultiplexers.
AB  - Novel multiplexers-demultiplexers for dense wavelength-division multiplexing
      systems that use interleaved sampled gratings are presented. It is shown that,
      with the appropriate design, configurations ranging from hybrid to add-drop as
      well as all-grating-based multiplexers can easily be realized.

PMID- 18079832
TI  - Grating resonances in air-silica microstructured optical fibers.
AB  - We report what is believed to be the first demonstration of optical fiber
      gratings written in photonic crystal fibers. The fiber consists of a germanium
      doped photosensitive core surrounded by a hexagonal periodic air-hole lattice in
      a silica matrix. The spectra of these gratings allow for a detailed
      characterization of the fiber. In particular, the gratings facilitate coupling to
      higher-order leaky modes. We show that the spatial distribution and the effective
      index of these modes are determined largely by the design of the lattice and that
      the grating spectra are unaffected by the refractive index surrounding the fiber.
      We describe these measurements and corresponding simulations and discuss their
      implications for the understanding of such air-hole structures.

PMID- 18079833
TI  - Localization in frequency for periodically kicked light propagation in a
      dispersive single-mode fiber.
AB  - We show a special effect of localization in the temporal frequency domain of
      light pulses that propagate in a dispersive single-mode fiber in the presence of
      a time-periodic phase modulation that is repeatedly applied at equally spaced
      locations along the fiber. The effect is analogous to the dynamical localization
      that occurs for the quantum kicked rotor, which is similar to Anderson
      localization in disordered solids. The wave behavior eliminates the diffusive
      spread of sidebands (harmonics). The light propagation, which is described by a
      Schrodinger-like propagation equation, can provide a new testing ground for the
      investigation of localization besides shedding light on technologically important
      pulse propagation in fibers and mode-locked lasers.

PMID- 18079834
TI  - Loop-mirror filters based on saturable-gain or-absorber gratings.
AB  - We present a novel all-fiber narrow-band filter based on pump-induced saturable
      gain or-absorber gratings in a loop mirror. Our design provides built-in
      interferometric phase alignment of the signal to the grating for optimal
      filtering. Notch or bandpass functionality is determined by the choice of gain or
      absorption and the input ports selected for the pump and signal. The loop-mirror
      filter has potential bandwidths from the submegahertz to beyond the gigahertz
      regimes, and one can tune it optically by changing the wavelength of the pump
      light that establishes the grating. Such filters have potential applications to
      wavelength-division-multiplexed optical networks and optical rf signal
      processing.

PMID- 18079835
TI  - Optical correlation with totally incoherent light.
AB  - An optical correlator that can operate with totally incoherent light is
      presented. Such a correlator can be designed to compensate completely for the
      inherent chromatic aberrations by resorting to elements with specialized,
      possibly impractical, dispersion characteristics. Nevertheless, a practical
      configuration that exploits available achromatic lenses and Fresnel zone plates
      was designed, built, and tested experimentally. The results reveal that
      detectable correlation peaks can be obtained with totally incoherent white light.
      The designs, experimental procedures, and results are presented.

PMID- 18079836
TI  - Efficient phase estimation for large-field-of-view adaptive optics.
AB  - We propose a maximum a posteriori-based estimation of the turbulent phase in a
      large field of view (FOV) to overcome the anisoplanatism limitation in adaptive
      optics. We show that, whatever the true atmospheric profile, a small number of
      equivalent layers (two or three) is required for accurate restoration of the
      phase in the whole FOV. The implications for multiconjugate adaptive optics are
      discussed in terms of the number and conjugated heights of the deformable
      mirrors. The number of guide stars required for wave-front measurements in the
      field is also discussed: three (or even two) guide stars are sufficient to
      produce good performance.

PMID- 18079837
TI  - Spectroscopic polarimetry with a channeled spectrum.
AB  - We describe a novel method for the spectroscopic measurement of the state of
      polarization (SOP) of light. A pair of thick birefringent retarders is
      incorporated into the spectroscopic polarimeter, so the generated channeled
      spectrum is composed of three quasi-cosinusoidal components carrying the
      information about the SOP of the light that is being measured. Fourier inversion
      of the channeled spectrum provides significant parameters for determination of
      the spectrally resolved Stokes parameters of light. No mechanically movable
      components for polarization control or active devices for polarization modulation
      are used, and all the Stokes parameters can be determined at once from only the
      single spectrum. The effectiveness of this method is demonstrated by the
      generation of elliptically polarized light whose SOP varies with wave number.

PMID- 18079838
TI  - Beam-splitting ball lens: a new integrated optical component.
AB  - A beam-splitting ball lens is introduced as a new integrated optical component
      for board- and backplane-level optical interconnection applications. The proposed
      beam-splitting ball lenses can be used in conjunction with polymer fiber image
      guides to split and combine imaged patterns of two-dimensional array optical
      data. Power and resolution performance parameters of a packaged system are
      presented.

PMID- 18079840
TI  - Optimal interferometer designs for optical coherence tomography.
AB  - We introduce a family of power-conserving fiber-optic interferometer designs for
      low-coherence reflectometry that use optical circulators, unbalanced couplers,
      and (or) balanced heterodyne detection. Simple design equations for optimization
      of the signal-to-noise ratio of the interferometers are expressed in terms of
      relevant signal and noise sources and measurable system parameters. We use the
      equations to evaluate the expected performance of the new configurations compared
      with that of the standard Michelson interferometer that is commonly used in
      optical coherence tomography (OCT) systems. The analysis indicates that improved
      sensitivity is expected for all the new interferometer designs, compared with the
      sensitivity of the standard OCT interferometer, under high-speed imaging
      conditions.

PMID- 18079839
TI  - Polymer relaxations determined by use of a temporally and thermally stable
      interferometer.
AB  - We describe a phase-controlled, highly stable interferometer that is ideal for
      use in long-time and high-temperature studies. We recorded output intensity
      variations of <0.2% for over 6 h at temperatures up to 150 degrees C. The setup
      was used to study in situ the temperature and frequency characteristics of a thin
      polymer film composed of 4-dimethylamino-4?-nitrostilbene doped into poly(methyl
      methacrylate). The mobility of the dopant molecules, which governed the electro
      optic property of the film, was used to probe the dye-doped polymer's rheology.
      We demonstrate one application of the interferometer in probing both the alpha
      and the beta relaxations of the polymer.

PMID- 18079841
TI  - Planar Bragg gratings made by excimer-laser modification of ion-exchanged
      waveguides.
AB  - The refractive indices of planar silver-ion-exchanged waveguides have been
      modified by UV excimer laser irradiation (lambda=193 nm) . The effective index
      changes of the fundamental modes of the waveguides after exposition are as large
      as 2x10(-2) . The procedure permits the fabrication of integrated optical
      components in a direct way, with neither the use of standard lithography nor
      previous sensitizing of the substrate. Optical characterization of the irradiated
      samples is presented. By the use of appropriate masks, we have fabricated planar
      Bragg gratings.

PMID- 18079842
TI  - Efficient all-solid-state yellow laser source producing 1.2-W average power.
AB  - We report a practical and efficient all-solid-state laser source operating at 578
      nm. The source comprises a diode-pumped Nd:YAG laser gain medium producing
      fundamental output at 1064 nm, an intracavity LiIO (3) Raman-active crystal that
      generates first-Stokes output at 1155 nm, and an intracavity LiB(3)O(5) frequency
      doubling crystal, which frequency doubles the first-Stokes output to 578 nm. Q 
      switched output with as much as 1.2-W average power has been obtained; conversion
      efficiencies from the fundamental to the yellow as high as 33% have been
      obtained.

PMID- 18079843
TI  - Frequency-sweep generation by resonant self-injection locking.
AB  - We report a novel application of self-injection locking. A diode laser is
      injection locked to its own frequency-shifted emission. By resonant phase
      modulation of the fed-back light, the laser's emission frequency is shown to
      swing periodically through the locking range. The laser operates as a sweep
      generator driven by resonant self-injection locking.

PMID- 18079844
TI  - Synchronous, dual-wavelength, injection-seeded amplification of 5-ns pulses in a
      flash-lamp-pumped Ti:sapphire laser.
AB  - The outputs of two cw diode lasers are coupled into a flash-lamp-pumped
      Ti:sapphire laser cavity for regenerative amplification. Slices of each seed beam
      are simultaneously trapped in the cavity and amplified for approximately 33 round
      trips. The output is a 4.7-ns pulse, the total pulse energy is 110 mJ, and
      linewidths are only 50% greater than the Fourier-transform limit. The timing
      jitter between the pulses at the two wavelengths is less than +/-75 ps , and
      their relative energy is controlled by adjustment of the seed power of the cw
      diode lasers. Gain competition between the two frequencies does not lead to
      instabilities.

PMID- 18079845
TI  - Frequency locking a laser to an optical cavity by use of spatial mode
      interference.
AB  - We present a novel technique to frequency lock a laser to an optical cavity. This
      technique, tilt locking, utilizes a misalignment of the laser with respect to the
      cavity to produce a nonresonant spatial mode. By observing the interference
      between the carrier and the spatial mode one can obtain a quantum-noise-limited
      frequency discriminator. Tilt locking offers a number of potential benefits over
      existing locking schemes, including low cost, high sensitivity, and simple
      implementation.

PMID- 18079846
TI  - Synthesized optical coherence tomography for imaging of scattering objects by use
      of a stepwise frequency-modulated tunable laser diode.
AB  - A technique named synthesized optical coherence tomography (SOCT) has been
      proposed and developed as an alternative method to the well-known optical
      coherence tomography for cross-sectional imaging of scattering objects. SOCT is
      based on the principle of synthesis of an optical coherence function by use of a
      tunable laser diode. With stepwise frequency modulation of light and synchronous
      phase modulation, the coherence function is synthesized into a peak at an
      arbitrary location. The longitudinal scattering distribution of the object under
      test is thus obtained without a mechanically driven reference. Two-dimensional
      tomography was demonstrated in a basic experiment with a lateral mechanical scan.

PMID- 18079847
TI  - Resolution improvement by nonconfocal theta microscopy.
AB  - We present a novel scanning fluorescence microscopy technique, nonconfocal theta
      microscopy (NCTM), that provides almost isotropic resolution. In NCTM,
      multiphoton absorption from two orthogonal illumination directions is used to
      induce fluorescence emission. Therefore the point-spread function of the
      microscope is described by the product of illumination point-spread functions
      with reduced spatial overlap, which provides the resolution improvement and the
      more isotropic observation volume. We discuss the technical details of this new
      method.

PMID- 18079848
TI  - Fast, reconfigurable light-induced waveguides.
AB  - Fast and reconfigurable one-dimensional waveguides are produced by interband
      photorefraction. The index barriers are induced by ultraviolet light. The guiding
      of a red laser beam with a full width at half-maximum of 15 mum is demonstrated.
      Buildup and decay times of the waveguide in pure KNbO(3) are of the order of 100
      mus and 10 ms, respectively. The intensity of the guided light has no influence
      on the guiding properties over the range from 4 mW/cm(2) to 200 W/cm(2) . By
      reconfiguration of the waveguide, deflection angles of as much as 1.75 deg inside
      the crystal are achieved.

PMID- 18079849
TI  - Spontaneous hexagon formation in photorefractive crystal with a single pump wave.
AB  - A new scheme for spontaneous formation of hexagonal optical patterns in
      photorefractive crystals with dominant reflection gratings and a single pump wave
      is proposed and realized experimentally. It is shown theoretically that
      spontaneous hexagon formation results from random small-angle scattering of the
      pump wave inside the crystal. The threshold of spontaneous hexagon formation is
      found.

PMID- 18079850
TI  - Optical parametric generation and phase matching in magneto-optic media.
AB  - We derive the equations and main characteristics of optical parametric generation
      in magneto-optic media. The key performances are discussed in terms of Stokes
      parameters and conservation laws of electromagnetic linear and angular momentum.

PMID- 18079851
TI  - Quadratic solitons in nonconservative media.
AB  - We develop a perturbation theory for the evolution of solitary waves in quadratic
      nonconservative nonlinear media. The expressions derived for the solitons'
      amplitude and width permit us to estimate straightforwardly the damping
      amplification rate of an arbitrary soliton of the unperturbed system. The
      analytical results obtained agree well with numerical experiments.

PMID- 18079852
TI  - Nonlinear spatially resolved phase spectroscopy.
AB  - A new method for the determination of spatially resolved phase differences of
      nonlinear susceptibilities is presented. The technique is based on the
      interference of the signal field with a reference field. A phase-shifting element
      that directly changes the phase difference between the two second-harmonic fields
      is introduced. The reliability of the method is tested by an experiment with two
      quartz crystals. As a first application, a measurement of the phase difference
      between domains in antiferromagnetic YMnO(3) is presented.

PMID- 18079853
TI  - High-repetition-rate ultrashort-pulse optical parametric oscillator continuously
      tunable from 2.8 to 6.8 mum.
AB  - We describe a synchronously pumped femtosecond optical parametric oscillator
      based on periodically poled LiNbO(3) that is broadly tunable in the mid infrared.
      A transmission window of periodically poled lithium niobate beyond the
      conventionally accepted infrared absorption edge of 5.4 mum has been exploited to
      produce idler pulses that are tunable across a wavelength range of 4 mum , with
      milliwatt-level output powers at wavelengths as long as 6.8 mum . We also present
      experimental tuning results that are in good agreement with the theoretical phase
      matching predicted from published infrared-corrected Sellmeier equations for
      LiNbO(3) .

PMID- 18079854
TI  - Spatially distributed spectral storage.
AB  - A new technique for overcoming the effects of excitation-induced frequency shifts
      in swept-carrier optical memories is proposed and demonstrated. Spectral storage
      capacity increases of more than 2 orders of magnitude were achieved through
      implementation of the method.

PMID- 18079855
TI  - Mirror-dispersion-controlled sub-10-fs optical parametric amplifier in the
      visible.
AB  - Pulses from an optical parametric amplifier in the visible are compressed to sub
      10-fs duration by a delay line made exclusively from chirped dielectric mirrors.
      We employ what we believe are the first ultrabroadband visible chirped mirrors,
      which provide negative group-delay dispersion up to the blue-green spectral
      region. The setup is compact and reliable, and we used it to observe, for what is
      to our knowledge the first time in organic molecules, coherent oscillations with
      periods as short as 16 fs.

PMID- 18079856
TI  - Implementation of spectral phase interferometry for direct electric-field
      reconstruction with a simultaneously recorded reference interferogram.
AB  - An improvement of the technique of spectral phase interferometry for direct
      electric-field reconstruction is presented. The possibility of simultaneously
      recording two interference spectra, one containing complete information on the
      spectral amplitude and the other containing complete information on the spectral
      phase, on a single one-dimensional detector is demonstrated. This is, to the
      author's knowledge, the only method that permits the complete characterization of
      an ultrashort light pulse with a single one-dimensional integrating detector and
      an algebraic inversion procedure.

PMID- 18079857
TI  - Transverse-electric and transverse-magnetic beam modes beyond the paraxial
      approximation.
AB  - Transverse-electric and transverse-magnetic beam modes are considered based on a
      theory in which complex dipole sources and sinks are oriented along the beam
      axis; the theory is similar to one that was previously presented for transverse
      dipoles. The field in the region of the waist is explored. Modes with such
      polarization have been reported from a wide range of laser types.

PMID- 18079858
TI  - Three-dimensional electric-field vector measurement with an electro-optic sensing
      technique.
AB  - A new technique for three-dimensional (3D) electric-field (e-field) vector
      measurement is presented. Three laser beams with different propagation paths in
      an electro-optic (EO) crystal were used to resolve 3D components of e-field
      vectors. We adopted a special geometric shape of bismuth silicon oxide EO crystal
      so that the three beams would propagate within it. A sensitivity of 0.6 V/cm
      square root Hz was achieved. A commercial Ansoft Maxwell 3D field simulator was
      also used to verify our measurements.

PMID- 18079859
TI  - Fluorine-doped SiO2 glasses for F2 excimer laser optics: fluorine content and
      color-center formation.
AB  - Color-center formation in F-doped, OH-free synthetic SiO(2) glasses by
      irradiation with F(2) excimer lasers (157 nm) was examined as a function of the F
      content. The concentration of photoinduced E(') centers was reduced to
      approximately 1/20 by 1 mol.% F(2) doping and remained almost constant on further
      doping to 7.3 mol. %. The absorption edge was considerably shifted to a lower
      wavelength (157.4 nm -->153 nm for a 5-mm-thick sample) by 1-mol. % doping and
      decreased only slightly on further doping. The intensities of the Raman bands
      that are due to three- and four-membered ring structures were significantly
      reduced by 1-mol. % F doping. These results strongly suggest that elimination of
      strained Si-O-Si bonds by F doping plays a central role in the improvement of
      radiation resistance of SiO(2) glasses to F(2) laser light.

PMID- 18079860
TI  - Optical detection of cold atoms without spontaneous emission.
AB  - We have demonstrated nondestructive detection of cold atoms with a probe laser by
      a frequency-modulation spectroscopy technique. We were able to tune the probe
      laser and its sidebands far from atomic resonance to reduce the spontaneous
      emission to less than 0.2 photon per atom during detection.

PMID- 18079861
TI  - Multistage dispersion compensator using ring resonators.
AB  - A compact, multichannel dispersion-compensating filter is demonstrated with D=
      4200 ps/nm, a +/-5-ps group delay ripple, <3-dB loss, and a 4.5-GHz passband
      width out of a 12.5-GHz free spectral range. We show that multistage designs can
      achieve a substantial increase in passband width and peak dispersion for a given
      group-delay ripple compared with single-stage designs. The dispersion
      compensation effectiveness was demonstrated in a 320-km, seven-channel nonlinear
      system simulation for OC48 signals.

PMID- 18079862
TI  - Superchirped moire grating based on an acousto-optic superlattice with a chirped
      fiber Bragg grating.
AB  - A superchirped moire grating has multiple superimposed chirped Bragg gratings. We
      show that a superchirped moire grating can be formed in an acousto-optic
      superlattice with a chirped fiber Bragg grating. There are multiple transmission
      peaks related to Fabry-Perot resonance in the transmission spectrum. The peak
      spacing is varied by the acoustic frequency. The proposed devices can be used as
      tunable multiple-passband transmission filters and switches.

PMID- 18079863
TI  - Raman-assisted parametric frequency conversion in a normally dispersive single
      mode fiber.
AB  - We demonstrate efficient frequency conversion with large frequency shifts of an
      anti-Stokes signal into a parametrically seeded Stokes idler, which is generated
      by a highly mismatched three-wave mixing interaction and subsequent Raman
      amplification in a normally dispersive single-mode fiber. The use of non-phase
      matched waves in Raman-assisted three-wave mixing interactions overcomes the
      strict spectral limitations imposed by phase-matching conditions in parametric
      frequency-conversion processes.

PMID- 18079864
TI  - Generation of a 64-GHz, 3.3-ps transform-limited pulse train from a fiber laser
      employing higher-order frequency-modulated mode locking.
AB  - We demonstrate the generation of optical pulses at a repetition rate of 64 GHz
      directly from a frequency-modulated (FM) mode-locked fiber laser. This is
      achieved by phase modulation at 16 GHz and by initiating of higher-order FM mode
      locking by use of an intracavity Fabry-Perot filter with a free spectral range of
      64 GHz. This process yielded transform-limited pulses with a width of 3.3 ps. We
      investigated the operating characteristics of the laser and compared them with
      the characteristics that were predicted theoretically.

PMID- 18079865
TI  - Self-starting mode locking of a Nd:glass fiber laser by use of the third-order
      nonlinearity of low-temperature-grown GaAs.
AB  - We present a diode-pumped Nd:glass fiber laser, emitting at 1060 nm, that is
      passively mode locked by fast nonlinear loss in low-temperature-grown GaAs (LT
      GaAs). This new mode-locking mechanism is based on intensity-dependent defocusing
      in LT-GaAs that occurs after nonresonant generation of free carriers by two
      photon absorption. Mode locking is self-starting and produces pulses as short as
      4.1 ps.

PMID- 18079866
TI  - Experimental synchronization of chaotic oscillations in externally injected
      semiconductor lasers in a low-frequency fluctuation regime.
AB  - Synchronization of chaotic oscillations between external-cavity and injected
      semiconductor lasers is experimentally observed in a low-frequency fluctuation
      regime. Not only from the occurrence of power drop events between their waveforms
      but also from the detailed structures of mode transition in power recovery
      processes of low-frequency fluctuations, it is confirmed that the two systems are
      synchronized in coherence-collapse states.

PMID- 18079867
TI  - Electronically tunable external-cavity laser diode.
AB  - We present a new concept for an electronically tunable diode laser. It is based
      on an external-cavity configuration with simultaneous feedback and intracavity
      spatial separation of the laser's spectral components. The electronical
      tunability is achieved by insertion of a liquid-crystal array as an
      electronically controlled aperture into the region of spatial separation of the
      spectral components. Wavelength tunability without mechanical movement over a
      range of 10 nm and two-color operation are demonstrated with a 670-nm laser
      diode.

PMID- 18079868
TI  - Efficient grating-tuned mid-infrared Cr2+:CdSe laser.
AB  - Room-temperature, all-solid-state, broadly tunable laser operation of Cr(2+) 
      doped CdSe has been demonstrated. Pumping with a Q -switched Tm, Ho:YLF laser
      running at a 1-kHz repetition rate achieved broadband output of 500 mW at 2.6
      microm with 48% absorbed power slope efficiency. With reduced efficiency, as much
      as 815 mW of power was obtained. With a diffraction grating, the Cr(2+): CdSe
      laser was tuned from 2.3 to 2.9 microm with 10-nm bandwidth (FWHM) and output
      power up to 350 mW.

PMID- 18079869
TI  - Directly diode-pumped tunable continuous-wave room-temperature Cr4+:YAG laser.
AB  - We report what is to our knowledge the first directly diode-pumped tunable (over
      120 nm) continuous-wave Cr(4+): YAG laser, operating near 1.5 microm . At room
      temperature the laser delivered as much as 200 mW of power at 4 W of absorbed
      pump power. We also report observation of slow laser output degradation and
      bleaching in highly concentrated crystals, which we suggest is due to a
      photorefractive phenomenon.

PMID- 18079870
TI  - Production and characterization of Ti:sapphire thin films grown by reactive laser
      ablation with elemental precursors.
AB  - Crystalline Ti:sapphire (Ti:Al(2)O(3)) thin films were grown at low temperatures
      upon Al(2)O(3) (0001) substrates by reactive crossed-beam laser ablation at 248
      nm by use of a liquid Ti-Al alloy target and O(2) . The films were investigated
      ex situ by x-ray diffraction, x-ray photoelectron spectroscopy, and Rutherford
      backscattering spectrometry. Low-temperature luminescence was identical to that
      for Ti(3+) ions in bulk samples of Al(2)O(3) .

PMID- 18079871
TI  - High-flow-velocity and shear-rate imaging by use of color Doppler optical
      coherence tomography.
AB  - Color Doppler optical coherence tomography (CDOCT) is capable of precise velocity
      mapping in turbid media. Previous CDOCT systems based on the short-time Fourier
      transform have been limited to maximum flow velocities of the order of tens of
      millimeters per second. We describe a technique, based on interference signal
      demodulation at multiple frequencies, to extend the physiological relevance of
      CDOCT by increasing the dynamic range of measurable velocities to hundreds of
      millimeters per second. The physiologically important parameter of shear rate is
      also derived from CDOCT measurements. The measured flow-velocity profiles and
      shear-rate distributions correlate very well with theoretical predictions. The
      multiple demodulation technique, therefore, may be useful to monitor blood flow
      in vivo and to identify regions with high and low shear rates.

PMID- 18079872
TI  - Near-field effects of focused illumination on periodic structures in scanning
      tunneling optical microscopy.
AB  - The influence of a focused polarized Gaussian beam on image formation was
      studied. We show that the position of the tip with reference to the center of the
      beam involves asymmetry in the intensity map. A comparison between s and p
      polarization can be made, owing to the definition of both a three-dimensional
      polarized Gaussian beam and a three-dimensional object. This result implies that
      the best way to scan a sample consists in moving it and not the tip; moreover,
      focusing the incident light to get a higher signal-to-noise ratio must be done
      carefully with respect to the sample period.

PMID- 18079873
TI  - 31%-efficient blue second-harmonic generation in a periodically poled MgO:LiNbO3
      waveguide by frequency doubling of an AlGaAs laser diode.
AB  - We present a method of controlling the shape of the domain-inverted structure in
      an off-cut MgO:LiNbO(3) crystal by utilizing a two-dimensional high-voltage
      application. With this technique a periodically domain-inverted structure with a
      period of 3.2 microm and a thickness of 2.0 microm was fabricated over a 10-mm
      interaction length. This structure has made possible sufficient overlaps between
      propagation modes and domain inversion in the waveguide. Using this structure, we
      demonstrated cw blue second-harmonic generation of 17.3 mW of power at a
      wavelength of 426 nm with single-pass 55-mW cw AlGaAs laser diode input, which
      corresponded to 31% power-conversion efficiency.

PMID- 18079874
TI  - Nonlinear frequency response of a moving grating with an applied field in bismuth
      silicon oxide.
AB  - A fully nonlinear frequency response of a moving grating in bismuth silicon
      oxide, including the effects of an applied electric field, is modeled by solution
      of the time-dependent Kukhtarev equations for photorefractive materials. The
      numerical results are used to define fully the nonlinear response function
      F(m)=a(-1)[1-exp(-am)], where m is the modulation index in the intensity pattern,
      to yield the unknown quantity a over a broad range of detuning frequencies f .
      For low f, the response is superlinear with a<0, and for relatively large f it is
      sublinear with a>0 . In the midrange we predict, for the first time to our
      knowledge, a characteristic frequency f(l) at which a=0 and the response is
      linear, that is, F(m) approximately m, despite the presence of nonlinearly
      generated higher harmonics of the fundamental grating wave number. In view of
      this linear behavior, writing a hologram at the linear-response frequency f(l)
      might permit a more faithful reproduction of an object than that which is
      possible by writing at the frequency of maximum response at the resonance.

PMID- 18079875
TI  - Polarization-dependent laser-induced grating measurements.
AB  - The formation of electrostrictive gratings during laser-induced grating (LIG)
      experiments is considered in an electromagnetic rather than an electrostatic
      approach. A different form of the relation that was used previously for the
      electrostrictive pressure was achieved. The theoretical findings were
      experimentally verified by polarization-dependent LIG spectroscopy measurements
      of a mixture of nitrogen with methanol vapor at high pressure with 1064-nm
      radiation. Conditions for suppressing the contribution of the electrostrictive
      grating relative to that of the simultaneously generated thermal grating signals
      were found theoretically and experimentally. The technique can potentially
      increase detection sensitivity for population gratings in high-density gas
      mixtures.

PMID- 18079876
TI  - Scaling law for second-order hyperpolarizability in poly(triacetylene) molecular
      wires.
AB  - Poly(triacetylenes) are rodlike molecules with electrons delocalized over a one
      dimensional path. We show that they exhibit a power-law dependence of the second
      order hyperpolarizability gamma on the monomer unit n for short molecules and a
      smooth saturation toward a linear increase in longer molecules. The power law of
      gamma?n(a) with a approximately 2.5 from dengenerate four-wave mixing and third
      harmonic generation measurements is in good agreement with quantum-chemical
      calculations. The critical conjugation length for saturation in the three cases
      is shown to be approximately 60 carbon-carbon bonds, which indicates the upper
      boundary for the electron delocalization in such a one-dimensional molecular
      wire.

PMID- 18079877
TI  - Single-frequency continuous-wave radiation from 0.77 to 1.73 microm generated by
      a green-pumped optical parametric oscillator with periodically poled LiTaO3.
AB  - We describe a cw optical parametric oscillator (OPO) with multigrating
      periodically poled LiTaO(3) . Pumped by a single-frequency 532-nm laser, the OPO
      emits single-frequency radiation at wavelengths from 0.77 to 1.73 microm with as
      much as 60 mW of output power. Mode-hop-free operation for as long as 50 min, a
      low frequency drift (<70 MHz/h), and as much as 700-MHz continuous frequency
      tuning of signal and idler are demonstrated.

PMID- 18079878
TI  - Practical scheme for polarization-insensitive and frequency-conversion interval
      independent four-wave mixing in semiconductor optical amplifiers.
AB  - A practical scheme for polarization-insensitive and frequency-conversion interval
      independent four-wave mixing in an optical loop configuration is proposed that
      uses one conventional semiconductor optical amplifier device and two
      perpendicular polarized pump sources. The significant advantages of this
      technique are simplicity of configuration, efficient conjugate power generation,
      effective suppression of the signal and one pump wave at the output port, and
      reduction in noise.

PMID- 18079879
TI  - Nanosecond periodically poled lithium niobate optical parametric generator pumped
      at 532 nm by a single-frequency passively Q-switched Nd:YAG laser.
AB  - We report an efficient, visible, nanosecond optical parametric generator of
      periodically poled lithium niobate pumped at 532 nm by a frequency-doubled, diode
      pumped, passively Q -switched, single-mode Nd:YAG laser with 90-muJ pulse energy.
      The signal radiation is tunable from 637 to 593 nm. The maximum signal-conversion
      efficiency is 23%. Optical parametric amplification of a He-Ne laser at 632.8 nm
      is also studied.

PMID- 18079880
TI  - Intracavity second-harmonic and sum-frequency generation with a laser-diode
      pumped multitransition-oscillation LiNdP4O12 laser.
AB  - Efficient simultaneous intracavity second-harmonic and sum-frequency generation
      that is free from irregular large amplitude fluctuations (the so-called green
      problem) is achieved with a laser-diode-pumped LiNdP(4)O(12) (LNP) laser with a
      type II phase-matching KTiOPO(4) crystal. Observed frequency-mixing operations
      result from the simultaneous single-frequency oscillations on different
      transitions that arise from the wide fluorescence linewidth in a stoichiometric
      LNP laser that possesses inherently high Nd concentrations. Sum-frequency
      generation has been shown to arise from the interaction of oscillating
      longitudinal modes that belong to different transitions. A promising application
      to coherent terahertz-wave radiation by use of photomixers is proposed.

PMID- 18079881
TI  - Compact, actively Q-switched optical parametric oscillator.
AB  - An ultracompact, actively Q -switched optical parametric oscillator (OPO) has
      been realized that is only 30 mm in length, based on a semimonolithic microchip
      laser, a quadrupole deflector, and a monolithic periodically poled lithium
      niobate crystal. The OPO threshold was 550 mW when Nd:YAG was used as the gain
      material and 590 mW for Nd:Y VO(4), giving signal pulses of as much as 8.7 muJ in
      energy with Nd:YAG at 1 kHz and 5.9-muJ pulses with Nd:Y VO(4) at 5 kHz, for 1.2-
      and 2-W laser diode pumping, respectively. The output was single frequency and
      could be tuned over the range 1540-3440 nm.

PMID- 18079882
TI  - Nonlinear directional coupler in periodically poled lithium niobate.
AB  - Nonlinear wave propagation was investigated experimentally in coupled waveguides
      by means of the cascaded nonlinearity in quasi-phase-matched second-harmonic
      generation. With a specially designed wave-vector-mismatch distribution along the
      propagation axis, cascading was optimized for low fundamental depletion. High
      contrast, ultrafast all-optical switching with switching powers of tens of watts
      was observed.

PMID- 18079883
TI  - Highly efficient degenerate four-wave mixing with multipass geometries in a
      polymer laser dye saturable amplifier.
AB  - We demonstrate the use of highly efficient degenerate four-wave mixing for phase
      conjugation with multipass geometries in a polymer laser dye saturable amplifier.
      Phase-conjugate energy reflectivity of as much as 20,000% with a four-pass
      geometry in the longitudinally pumped polymer dye was obtained at 564 nm.

PMID- 18079884
TI  - Transient stimulated Raman scattering in gas mixtures.
AB  - We studied, for the first time to our knowledge, transient stimulated Raman
      scattering in H(2)- D(2) and H(2)- CH(4) gas mixtures excited with 200-fs and 2
      ps, 390-nm pulses. Depending on the composition and partial pressure, of those
      gases, we observed approximately 40 output lines simultaneously. Under optimum
      conditions a conversion efficiency of as much as 8% in the combination Raman line
      at 556 nm was obtained in the H(2)- CH(4) gas mixtures. The difference between
      picosecond and femtosecond pumping is due to self-phase modulation and to
      generation of a spectral continuum in the latter. Our calculation of the ratio of
      the partial pressures is in a good agreement with the experimental results. A new
      method for measuring the unknown Raman scattering cross section of gas molecules
      is suggested.

PMID- 18079885
TI  - Fiber-coupled writing and reading in magneto-optical media.
AB  - Curie point writing and Kerr signal reading in magneto-optical disk media are
      accomplished with a flint glass single-mode fiber that connects the optical
      source (laser diode)-detector and the magneto-optical medium. The Kerr signal is
      detected sensitively with high stability against external disturbances such as
      stress and deformation of the fiber. This technique offers a simple, flexible,
      light, movable, and remotely settable means for signal processing of magneto
      optical devices.

PMID- 18079886
TI  - Lithographic antennas at visible frequencies.
AB  - The response of antenna-coupled thin-film Ni-NiO-Ni diodes to 633-nm helium-neon
      laser radiation is investigated. Although these detectors and their integrated
      dipole antennas are optimized for the detection of mid-infrared radiation, a
      polarization dependence of the measured response to visible radiation is
      observed. The strongest signals are measured for the polarization parallel to the
      dipole antenna axis, which demonstrates antenna operation of the device in the
      visible in addition to the expected thermal and photoelectric effects. The
      connection structure of the diode also resonates and contributes to the
      polarization-dependent signal. The receiving area of the dipole antenna is
      approximately 2 microm(2) .

PMID- 18079887
TI  - Soot-velocity measurements by particle vaporization velocimetry.
AB  - We demonstrate a new imaging technique for velocity measurements in particle
      laden flows. The technique, particle vaporization velocimetry, is a form of flow
      tagging based on laser vaporization of absorbing particles at defined locations
      in the flow. The locations of these tagged regions are then interrogated after a
      known delay to determine the convective velocity. Results are presented for
      vaporization of carbonaceous (soot) particles in a nonreacting gas jet and a
      hydrocarbon flame, with interrogation provided by either elastic scattering or
      laser-induced incandescence from the soot. The long lifetime of the tagged soot
      regions (>2 ms) allows measurements to be made over a wide range of velocities.

PMID- 18079888
TI  - Frequency structure in an electronically tuned Ti:sapphire laser: periodic
      appearance of static fringes in both homodyne and heterodyne Michelson
      interferometers.
AB  - Static interference fringes were observed repeatedly with changes of path
      difference in both homodyne and heterodyne Michelson interferometers. This unique
      coherence property of an electronically tuned Ti:sapphire laser with an
      intracavity acousto-optic tunable filter (AOTF) has revealed the frequency
      structure and dynamics of the laser field. The fact that static interference
      occurred in a heterodyne interferometer with unequal path lengths indicates
      backscattering of the intracavity laser field, suggesting that Brillouin-enhanced
      four-wave mixing occurs in the intracavity AOTF.

PMID- 18079889
TI  - Hidden instabilities in the Ti:sapphire Kerr lens mode-locked laser.
AB  - It is experimentally shown that pulse-to-pulse instabilities in the output of
      Kerr lens mode-locked Ti:sapphire lasers are usual and that they can affect some
      of the pulse variables (e.g., the spot size) and not others (e.g., pulse duration
      and energy). These instabilities are not detectable in the averaged signals (such
      as the autocorrelation of the pulse) that are customarily used for controlling
      the laser. But, if they are present but are disregarded, these instabilities have
      undesirable consequences in almost any application. A simple way to detect and
      eliminate the instabilities is described.

PMID- 18079890
TI  - Pulse timing stabilization of a mode-locked Cr:LiSAF laser.
AB  - The pulse repetition frequency of a mode-locked Cr:LiSAF laser has been
      stabilized to an electrical reference oscillator by use of an electrical feedback
      technique. The phase and frequency differences between the laser and the
      reference are detected by use of a digital phase detector, which overcomes the
      difficulties of a conventional double-balanced mixer. We obtained rms timing
      jitters of 20 fs (25 mHz-10 kHz) and 7 fs (25 mHz-1 kHz) relative to the
      reference.

PMID- 18079891
TI  - Single-shot real-time characterization of chirped-pulse amplification systems by
      spectral phase interferometry for direct electric-field reconstruction.
AB  - We characterize chirped-pulse amplification systems by using spectral phase
      interferometry for direct electric-field reconstruction. For the first time to
      the authors' knowledge, single-shot real-time operation has been obtained for
      this technique, leading to a fast and accurate optimization of these systems.

PMID- 18079893
TI  - Far field of polarization gratings.
AB  - In a recent Letter [Opt. Lett. 24, 584 (1999)], Gori analyzed polarization
      gratings and proposed using them as a tool to measure Stokes parameters. Most of
      his analysis dealt with the near field, but practical exploitation of his
      approach relies on the far field. A discussion focusing on the far field is
      presented, and recipes are suggested for actual implementations of such devices.

PMID- 18079894
TI  - Self-imaging in photonic crystals in a subwavelength range.
AB  - Self-imaging was observed in simulations and in microwave experiments that were
      performed on a face-centered cubic photonic crystal structure. The structure was
      composed of dielectric spheres that generally were smaller than the incident
      wavelength. Such self-imaging phenomena occurred along the direction of
      propagation and at distances smaller than the propagating wavelength.

PMID- 18079895
TI  - Enhancement of chi((2)) cascading processes in one-dimensional photonic bandgap
      structures.
AB  - We theoretically analyze the nonlinear phase shifts induced by cascaded
      chi((2)):chi((2)) processes in one-dimensional photonic bandgap structures. We
      find that the enhancement of the density of modes near the band edge, coupled
      with a suitable choice of relative phase mismatch, leads to a remarkable new
      effect: The relative phase shift of the fundamental field on transmission can be
      of the order of pi over a distance of 7mum , with input intensities of the order
      of only 10 MW/cm(2).

PMID- 18079896
TI  - Observation of phase-matched electromagnetic scattering in an active dielectric
      cylinder.
AB  - A theoretical investigation of oblique plane-wave electromagnetic scattering in
      an active dielectric cylinder predicted the existence of anomalous resonances at
      discrete plane-wave angles of incidence. These resonances may be understood as
      being due to a leaky-wave phase-matching boundary condition. Experiments were
      performed with active dielectric cylinders to confirm the existence of discrete
      resonances. Cross coupling between TE and TM modes was clearly detected for both
      active and passive scattering. Enhancement of active scattered field intensities
      was observed in experiments with finite-diameter pump and probe laser beams.
      Optical pumping of a dye solution was used to provide the gain.

PMID- 18079897
TI  - Nonreciprocal diffraction by spatial modulation of absorption and refraction.
AB  - Linear diffraction gratings that provide strongly asymmetric diffraction without
      surface modulation are created and studied. The spatial phase shift of the
      refractive-index grating relative to the absorption grating is the origin of
      nonreciprocal behavior.

PMID- 18079898
TI  - Technique for multiplying the repetition rates of periodic trains of pulses by
      means of a temporal self-imaging effect in chirped fiber gratings.
AB  - We show that a temporal effect that is equivalent to the spatial self-imaging
      (Talbot) effect applies to the reflection of periodic signals from linearly
      chirped fiber gratings. The effect can be used for multiplying the repetition
      frequency of a given periodic pulse train without distorting the individual pulse
      characteristics. The practical limit on the frequency-multiplication factor
      depends only on the temporal width of the individual pulse. Thus we demonstrate
      that a suitable combination of well-known techniques for short-pulse generation,
      such as pulse mode locking, and the technique proposed here allows us to obtain
      short-pulse trains with ultrahigh repetition rates (in the terahertz regime).
      Results from simulations show good agreement with those predicted by theory.

PMID- 18079899
TI  - Bit rate and pulse width dependence of four-wave mixing of short optical pulses
      in semiconductor optical amplifiers.
AB  - We investigate the saturation properties of four-wave mixing of short optical
      pulses in a semiconductor optical amplifier. By varying the gain of the optical
      amplifier, we find a strong dependence of both conversion efficiency and signal
      to-background ratio on pulse width and bit rate. In particular, the signal-to
      background ratio can be optimized for a specific amplifier gain. This behavior,
      which is coherently described in experiment and theory, is attributed to the
      dynamics of the amplified spontaneous emission, which is the main source of noise
      in a semiconductor optical amplifier.

PMID- 18079900
TI  - Improvement of the ultraviolet-proof property of silica glass fibers for ArF
      excimer-laser applications.
AB  - The effects of preirradiation by ArF excimer laser and thermal annealing on the
      transmission properties of a silica fiber were investigated. The durability of
      the fiber when it was exposed to ArF excimer laser irradiation was improved by
      preirradiation at room temperature and subsequent thermal annealing at 600
      degrees C.

PMID- 18079901
TI  - String data alignment by a spatial coding and moirA technique.
AB  - A method for string alignment is presented in which a moire technique is applied
      to one-dimensional spatial encoding patterns. String alignment, an essential
      operation in genome analysis, evaluates local similarity between sequences of
      bases or amino acids. The method uses a simple procedure to provide matching
      results for not only the same locus but also neighboring loci. Experimental
      verification shows the effectiveness of the proposed method.

PMID- 18079902
TI  - 1.50-mum-band gain-shifted thulium-doped fiber amplifier with 1.05- and 1.56-mum
      dual-wavelength pumping.
AB  - We propose and demonstrate a 1.50-mum- band gain-shifted thulium-doped fiber
      amplifier (TDFA) by using a novel dual-wavelength (1.05and1.56 -mum) pumping
      scheme for what we believe is the first time. By providing a small amount of 1.56
      mum power to a conventional upconversion-pumped TDFA, we successfully
      demonstrated a small-signal gain larger than 25 dB and a noise figure of 5 dB in
      a 1475-1510-nm band.

PMID- 18079903
TI  - Timing restoration dynamics in an actively mode-locked fiber ring laser.
AB  - Using electronic phase detection, we study the dynamics that govern pulse
      retiming in an actively mode-locked fiber laser. We compare the dynamics for
      amplitude and for phase modulation and identify the characteristic time constants
      for each case. The retiming dynamics for amplitude modulation are revealed as a
      first-order exponential decay, whereas for phase modulation the dynamics are
      those of a damped harmonic oscillator. We show that the measured time constants
      agree with predictions given by the soliton perturbation theory.

PMID- 18079904
TI  - Theory of linearly birefringent fibers: an alternative approach.
AB  - We tackle the theory of linearly birefringent single-mode dielectric fibers in
      terms of magnetic fields, instead of the usual electric fields. The new approach
      simplifies the analysis of the minor field component as a function of the radial
      coordinate. Several previous results are reconfirmed and unified. New closed-form
      expressions are found for the field in a fiber in which the physical index seen
      by the minor component matches, in a part of the cross section, the guided-mode
      equivalent index.

PMID- 18079905
TI  - Wavelength-scanning digital interference holography for optical section imaging.
AB  - We propose and experimentally demonstrate a simple digital holographic method
      that allows reconstruction of three-dimensional object images with a narrow depth
      of focus or axial resolution. A number of holograms are optically generated by
      use of different wavelengths spaced at regular intervals. The holograms are
      recorded on a digital camera and reconstructed numerically. Multiwavelength
      interference of the holograms results in images of the contour plane whose
      thickness can be made arbitrarily narrow. Objects at different distances from the
      hologram plane are imaged clearly and independently, with complete suppression of
      the out-of-focus images. The technique is available only in digital holography
      and should have useful applications in holographic microscopy.

PMID- 18079906
TI  - Global rainbow thermometry for droplet-temperature measurement.
AB  - Standard rainbow thermometry connects the scattering angle of the main rainbow
      maximum, generated by a single droplet, to the droplet's refractive index and
      thus to its temperature. Droplet nonsphericity influences the rainbow position
      and therefore degrades the quality of the droplet-temperature measurement. We
      propose global rainbow thermometry, which measures the average rainbow position
      that is created by multiple droplets and from which a mean temperature can be
      derived. The new technique aims at eliminating the nonsphericity effect. The
      principle of this method is presented, and a typical recorded image is discussed.

PMID- 18079907
TI  - Refractivity of nitrogen gas in the vacuum ultraviolet.
AB  - We have measured the refractivity of nitrogen gas in the ultraviolet and the
      vacuum ultraviolet, using a Fourier-transform spectrometer. A new two-term
      Sellmeier formula for the standard refractivity between 145 and 270 nm is
      derived.

PMID- 18079908
TI  - Measurement of trench depth by infrared interferometry.
AB  - Measurement and control of high-aspect-ratio structures such as dynamic random
      access memory trenches is an important step in the manufacture of modern memory
      devices. We present a novel technique based on infrared interferometry that has
      been implemented in manufacturing and is capable of measuring sub- 0.25-mum -wide
      and 10-mum -deep trenches nondestructively and with an accuracy of better than
      0.1mum .

PMID- 18079909
TI  - Miniaturized time-scanning Fourier transform spectrometer based on silicon
      technology.
AB  - We present a miniaturized Fourier transform spectrometer (FTS) based on optical
      microelectromechanical system technology. The FTS is a Michelson interferometer
      with one scanning mirror. A new type of electrostatic comb drive actuator moves
      the mirror. We have measured a nonlinearity of the driving system of +/-0.5 mum
      for a displacement of 38.5 mum . A method is presented to correct the spectrum to
      get rid of the nonlinearity. The driving reproducibility is +/-25 nm. The
      measured resolution of the spectrometer after the phase correction is 6 nm at a
      wavelength of 633 nm.

PMID- 18079910
TI  - Volume grating preferential-order focusing waveguide coupler.
AB  - A volume grating focusing waveguide coupler has been designed, fabricated, and
      tested. The volume grating is designed to couple a 633-nm wave guided in a single
      mode polyimide waveguide preferentially into the air cover. The beam is
      outcoupled normally to the surface of the waveguide and focused to a line 25 mm
      above the waveguide. The slanted-fringe volume grating is holographically
      recorded by the interference of two coherent 364-nm ultraviolet waves focused
      with a cylindrical lens to produce the chirped grating. The 1-mm-long volume
      grating coupler exhibits a preferential-coupling ratio of 0.98, a coupling
      efficiency of 95%, and an almost diffraction-limited focal line with a full width
      at half-maximum of 10.49mum.

PMID- 18079911
TI  - Underlying dynamics of the pedestal components in a modulated laser diode with
      noise.
AB  - We demonstrate that the pedestal components observed in the power spectra of a
      directly modulated laser diode, which were interpreted as a sign of instability
      of the periodic regime, are an indication of the coexistence of a chaotic regime
      with the periodic one. We present the underlying dynamics behind the rise of
      these pedestals, showing two different situations in which the pedestals appear.
      In both, a periodic regime coexists with another attractor, a saddle cycle in one
      case and a chaotic attractor in the other. The random fluctuations included in
      the laser diode model allow the coexisting attractors to merge in the observed
      behavior of the laser.

PMID- 18079912
TI  - Focusing of a tabletop soft-x-ray laser beam and laser ablation.
AB  - We focused the beam of a high-repetition-rate capillary-discharge tabletop laser
      operating at a wavelength of 46.9 nm, using a spherical Si/Sc multilayer mirror.
      The energy densities significantly exceeded the thresholds for the ablation of
      metals. Single-shot laser ablation patterns were used in combination with ray
      tracing computations to characterize the focused beam. The radiation intensity
      within the 2-mum -diameter central region of the focal spot was estimated to be
      approximately 10(11)W/cm(2), with a corresponding energy density of ~100 J/cm(2).

PMID- 18079913
TI  - Generation of 160-ps terawatt-power CO(2) laser pulses.
AB  - We have developed a three-stage CO(2) master-oscillator-amplifier system that
      produces 1.1 TW of peak power. The system generates 170 J of energy in a
      diffraction-limited 160+/-10ps pulse on the 10P(20) line. We also report the
      realization of a two-wavelength terawatt-peak-power CO(2) laser that can be tuned
      to an arbitrary pair of lines. A two-stage semiconductor switching system driven
      by a picosecond-pulse Nd:YAG laser was used to slice a short, low-power 10.6-mum
      pulse for amplification. A simple plasma shutter helped to compensate for gain
      narrowing in a final three-pass amplifier and to shorten the pulse.

PMID- 18079914
TI  - 4.0-4.5-mum lasing of Fe:ZnSe below 180 K, a new mid-infrared laser material.
AB  - Lasing of Fe:ZnSe is demonstrated, for the first time to the authors' knowledge,
      for temperatures ranging from 15 to 180 K. The output wavelength of the Fe:ZnSe
      laser was observed to tune with temperature from 3.98mum at 15 K to 4.54mum at
      180 K. With an Er:YAG laser operating at 2.698mum as the pump source, a maximum
      energy per pulse of 12muJ at 130 K was produced. Laser slope efficiencies of 3.2%
      at 19 K and 8.2% at 150 K were determined for an output coupling of 0.6%. A laser
      emission linewidth of 0.007mum at 3.98mum was measured at 15 K. Absorption and
      emission spectra and emission lifetimes for Fe:ZnSe are also discussed.

PMID- 18079915
TI  - Integrated optical biosensor for detection of multivalent proteins.
AB  - We have developed a simple, highly sensitive and specific optical waveguide
      sensor for the detection of multivalent proteins. The optical biosensor is based
      on optically tagged glycolipid receptors embedded within a fluid phospholipid
      bilayer membrane formed upon the surface of a planar optical waveguide. Binding
      of multivalent cholera toxin triggers a fluorescence resonance energy transfer
      that results in a two-color optical change that is monitored by measurement of
      emitted luminescence above the waveguide surface. The sensor approach is highly
      sensitive and specific and requires no additional reagents and washing steps.
      Demonstration of protein-receptor recognition by use of planar optical waveguides
      provides a path forward for the development of fieldable miniaturized biosensor
      arrays.

PMID- 18079916
TI  - Frequency-domain immersion technique for accurate optical property measurements
      of turbid media.
AB  - We demonstrate that absorption coefficient micro(a) and reduced scattering
      coefficient micro(s)(?) of a small turbid object can be measured to high accuracy
      with a frequency-domain immersion technique. For this technique the sample is
      immersed in a calibrated scattering medium and the optical properties are
      obtained from a differential measurement. Compared with conventional approaches,
      the immersion technique improves accuracy, minimizes variations owing to probe
      coupling and motion, reduces the effects of boundary conditions, and offers
      simple and rapid measurement once the immersion medium is calibrated. Accuracy
      tests of immersion-based measurements of micro(a) and micro(s)(?) agree with
      reference values to within 3.6% and 2.6%, respectively. These tests are limited
      by the accuracy of the reference samples rather than by the accuracy of the
      immersion medium or the precision of the immersion approach. We demonstrate the
      in vivo capabilities of the technique through time-resolved measurements of
      micro(a) and micro(s)(?) for a human hand during cuff occlusion on the upper arm.

PMID- 18079917
TI  - Nonuniqueness in optical tomography: relevance of the P1 approximation.
AB  - The question of whether a unique distribution of the absorption coefficient, the
      scattering coefficient, and the refractive index of a turbid medium can be
      reconstructed by optical tomography is considered. A recent publication [Opt.
      Lett. 23, 882 (1998)] established that such reconstruction is not possible when
      photon transport is well modeled by the diffusion equation. A simple proof is
      offered that, when measurements at high modulation frequencies are included, the
      more exact P1 model of light transport suggests that this reconstruction may be
      possible.

PMID- 18079918
TI  - Deconvolution of local surface response from topography in nanometer profilometry
      with a dual-scan method.
AB  - In profilometric measurements, by scanning the sample twice with a fixed vertical
      offset, one can separate the signal that comes from surface heterogeneity from
      the topographic signal. Using differential confocal microscopy, a newly developed
      open-loop nanometer profilometric technique, we demonstrated this dual-scan
      method on composite samples and obtained 10-nm depth resolution. This technique
      can also be applied to other profilometric techniques such as atomic force
      microscopy and scanning tunneling microscopy.

PMID- 18079919
TI  - Interactions and switching of spatial soliton pairs in the vicinity of a
      nonlinear interface.
AB  - The interaction of spatial soliton pairs with a nonlinear interface was studied
      theoretically. With mediation of the interface, the two solitons exhibited
      efficient switching and double switching. A closed-form particlelike model,
      validated by propagation calculations, yielded the soliton trajectories and
      switching characteristics.

PMID- 18079920
TI  - Soliton multistability as a result of double-resonance wave mixing in chi((2))
      media.
AB  - We investigate analytically and numerically the existence and stability
      properties of three-wave solitons resulting from double-resonance (type I plus
      type II) parametric interaction in a purely quadratic nonlinear medium. The
      existence of a family of stable solitons for the double-resonance model is
      demonstrated in a broad parameter range. Moreover, these solitons are shown to
      exhibit multistability, a feature that is potentially useful for optical
      switching applications. Finally, we find and present a novel family of quasi
      solitons.

PMID- 18079921
TI  - Effect of temperature and atmospheric environment on the photodegradation of some
      Disperse Red 1-type polymers.
AB  - The photodegradation of the azobenzene chromophore DR1 {4-[N-ethyl-N-(2
      hydroxyethyl)amino]-4(?)-nitroazobenzene]} incorporated as a side chain or as a
      guest in a poly(methyl) methacrylate host has been evaluated as a function of
      wavelength, temperature, and the atmospheric environment. The effects of these
      variables on the lifetime of DR1-based electro-optic devices is quantified.

PMID- 18079922
TI  - Broadband optical frequency comb generation with a phase-modulated parametric
      oscillator.
AB  - We introduce a novel broadband optical frequency comb generator consisting of a
      parametric oscillator with an intracavity electro-optic phase modulator. The
      parametric oscillator is pumped by 532-nm light and produces near-degenerate
      signal and idler fields. The modulator generates a comb structure about both the
      signal and the idler. Coupling between the two families of modes results in a
      dispersion-limited comb that spans 20 nm (5.3 THz). A signal-to-noise ratio of
      >30 dB in a 300-kHz bandwidth is observed in the beat frequency between
      individual comb elements and a reference laser.

PMID- 18079923
TI  - Electro-optic spectral tuning in a continuous-wave, asymmetric-duty-cycle,
      periodically poled LiNbO(3) optical parametric oscillator.
AB  - We demonstrate electro-optic spectral tuning in a continuous-wave periodically
      poled LiNbO(3) (PPLN) optical parametric oscillator (OPO). We achieve 8.91 cm(-1)
      of rapid spectral tuning, with a linear tuning rate of 2.89 cm(-1) /(kV/mm), by
      applying electric fields up to +/-1.5 kV/mm across the crystal while it is
      operating within the OPO. Intentionally poling the PPLN crystal with an
      asymmetric domain structure enables tuning, and numerical predictions closely
      match the experimental observations. The tuning is considerably larger than the
      typical operational bandwidth of the OPO, indicating that we are in fact shifting
      the gain curve of the PPLN crystal.

PMID- 18079924
TI  - Demonstration of partial erasing of picosecond temporal optical data by use of
      accumulated photon echoes.
AB  - We demonstrated partial erasing of temporal optical data on a picosecond time
      scale by use of accumulated photon echoes. In a photon-echo memory the temporal
      data at time tau are stored as a frequency grating of period 1/tau in the
      absorption spectrum of a material. Partial erasing of the temporal data is
      achieved by irradiation of the material with a pulse pair at time separation tau
      , but the phase of one of the pulses is shifted 180 degrees . This process does
      not produce a frequency grating, and no echo is emitted. The experiment was
      performed with a dye-doped polymer film. The 180 degrees phase shift was obtained
      by use of a half-wave plate.

PMID- 18079925
TI  - Optimized phase quantization for diffractive elements by use of a bias phase.
AB  - Many applications of diffractive phase elements involve the calculation of a
      continuous phase profile that is subsequently quantized for fabrication. The
      quantization process maps the continuous range of phase values to a limited
      number of discrete steps. We report our observation of the influence of this
      quantization process on the performance of mode-selecting diffractive elements
      and show that the quantization process produces significantly better results by
      use of an optimized bias phase. In principle this process can be employed to a
      greater or lesser extent in any quantization process.

PMID- 18079926
TI  - Behavior of cholesteric liquid crystals in a Fabry-Perot cavity.
AB  - We investigate the behavior of cholesteric liquid crystals (CLC's) inside a Fabry
      Perot (FP) cavity. Although FP cavities filled with various liquid crystals have
      been extensively studied, to our knowledge the behavior of CLC-based FP cavities
      has not been reported. In CLC the twisted structure can be changed because the
      pitch is a function of temperature. In a parallel-rubbed CLC FP cavity the
      balance between strong surface anchoring and elastic energy yield a steplike
      resonance spectrum. This corresponds to the quantized effective pitch that the
      system assumes when both surface alignments are fixed. Experiment results for
      parallel-rubbed samples are presented and explained theoretically by use of Jones
      matrix calculations.

PMID- 18079927
TI  - Correction of the quenching effect in two-dimensional laser-induced fluorescence
      measurement of laser-ablation processes.
AB  - Laser-induced fluorescence (LIF) and two-dimensional laser-induced fluorescence
      were used for measurement of the fluorescence lifetime of the A(1)?(+) state of
      BaO molecules in the laser-ablation process of BaTiO(3) and YBa(2)Cu(3)O(7-x) in
      the oxygen background gas. The zero-pressure lifetime and the quenching rate were
      also determined as tau(0)=357ns and k=5.1 x 10(-6)ns(-1)mTorr(-1) , respectively.
      The spatiotemporal changes of the collisional quenching of BaO molecules were
      successfully visualized, and the influence of the quenching on the spatial
      distribution imaging of BaO molecule was corrected.

PMID- 18079928
TI  - Self-starting mode-locked Cr(4+):YAG laser with a low-loss broadband
      semiconductor saturable-absorber mirror.
AB  - We report a self-starting mode-locked Cr(4+):YAG laser with a low-loss broadband
      metal reflector-based semiconductor saturable-absorber mirror. The minimum pulse
      width was 44 fs at a wavelength of 1520 nm.

PMID- 18079929
TI  - Direct measurement of a photoconductive receiver's temporal response by dithered
      edge sampling.
AB  - We present the results of a direct measurement of the temporal response of a
      terahertz (THz) photoconductive receiver obtained by dithered-edge sampling. The
      receiver response has structure that accounts for the negative-going leading edge
      of the pulse shape that is often seen in measurements made with these receivers
      in a conventional sampling arrangement. We show that the THz pulse shape measured
      by conventional photoconductive sampling is indeed a cross correlation of the
      pulse with the measured receiver's response.

PMID- 18079930
TI  - Full-field characterization of femtosecond pulses by spectrum and cross
      correlation measurements.
AB  - We present a practical and accurate technique for retrieving the amplitude and
      the phase of ultrashort pulses from a nonlinear (second-order) intensity cross
      correlation and the spectrum that overcomes shortcomings of previous attempts. We
      apply the algorithm to theoretical and experimental data and compare it with
      frequency-resolved optical gating.

PMID- 18079931
TI  - High-energy pulse compression by use of negative phase shifts produced by the
      cascade chi((2)):chi((2)) nonlinearity.
AB  - We report a simple optical pulse-compression technique based on quadratic
      nonlinear media. Negative nonlinear phase shifts are generated by phase
      mismatched second-harmonic generation, and the phase-modulated pulses are then
      compressed by propagation through materials with normal dispersion. Millijoule
      energy pulses from a Ti:sapphire amplifier are compressed from 120 to 30 fs, and
      calculations indicate that compression ratios of >10 are realistically achievable
      by use of this approach with optimal materials. The insertion loss of the
      compressor can be less than 10% of the pulse energy, and scaling to higher pulse
      energies will be straightforward.

PMID- 18079932
TI  - Second-harmonic generation frequency-resolved optical gating analysis of low
      intensity shaped femtosecond pulses at 1.55 mum.
AB  - We illustrate observation and characterization of medium- and low-intensity
      shaped ultrashort pulses at lambda=1.55mum through single-shot geometry
      (multishot-average) second-harmonic generation-frequency-resolved optical gating.
      The pulses are shaped by amplitude filters in the Fourier plane of a compact
      folded shaper. Sensitivity to pulses with energies of less than 20 pJ and high
      dynamic range is reported for this configuration. Application of this method to
      the propagation of ~170-fs pulses through a 50-m fiber link is also illustrated.

PMID- 18079933
TI  - Frequency-upconverted organic crystal.
AB  - The fluorescent characteristics of Troger's base have been investigated
      experimentally. A one-photon-induced fluorescent spectrum was observed, and the
      peak wavelength was at 337 nm with a full width at half-maximum of ~85nm . The
      violet radiation of the Troger's base crystal could result from the pi(*) -pi
      transition of the benzenoid pi bond. Two-photon-pumped frequency-upconverted
      fluorescence was obtained, which is a wideband emission with the main peak
      wavelength at 337 nm and a subordinate peak. Donor groups and acceptor groups of
      electrons in the aromatic rings strengthen the two-photon-pumped frequency
      upconverted fluorescence.

PMID- 18079934
TI  - Hartmann wave-front scanner.
AB  - A wave-front sensor is described that uses a programmable moving aperture to scan
      an incoming wave front. The position of the diffraction spot is recorded behind
      an objective lens with a two-dimensional sensor and gives an estimate of the
      local slope at the aperture position. Then the wave front is reconstructed by
      processing of the slope data. The device is basically a programmable Hartmann
      wave-front sensor. Compared with a microlens Shack-Hartmann wave-front sensor,
      its much longer focal length provides higher resolution, although real-time
      operation is lost. A practical implementation of the new scanner with a liquid
      crystal television as the programmable aperture is presented.

PMID- 18079935
TI  - Scalar diffraction of spherical waves by a plane aperture: a general analysis
      based on the critical points.
AB  - We present a formulation of the scalar diffraction of spherical waves through
      plane apertures that takes advantage of the importance of the critical points and
      the semiperiodic zones that are defined in the plane of the aperture. Our
      approach overcomes the intrinsic limitations of stationary-phase methods (when
      the critical points coalesce) and allows a direct implementation in terms of
      numerical algorithms for computations of any predefined accuracy. The method is
      illustrated with examples corresponding to a rectangular aperture.

PMID- 18079936
TI  - Piecewise smooth phase reconstruction.
AB  - A well-founded and computationally fast method is presented for filtering and
      interpolating noisy and discontinuous wrapped phase fields that preserves both
      the 2pi discontinuities that come from the wrapping effect and the true
      discontinuities that may be present. It also permits the incorporation of an
      associated quality map, if it is available, in a natural way. Examples of its
      application to the computation of the isoclinic phase from photoelastic data and
      to the recovery of discontinuous phase fields from speckle interferometry are
      presented.

PMID- 18079937
TI  - Long, narrow all-light atom guide.
AB  - A 1-mm-diameter all-light atom guide capable of transporting ultracold atoms tens
      of centimeters with high efficiency is described. We made the atom tunnel, a dark
      hollow beam that is blue detuned from resonance, by passing a few tens of
      milliwatts of energy from a TEM(00) diode laser beam through an optical sequence
      composed of three axicons and a simple lens. We demonstrate transport of 10(8)Cs
      atoms approximately 20 cm with minimal heating. We show that it is possible for
      one to control the direction and speed of the atoms in the tunnel by varying the
      detuning of the tunnel beam.

PMID- 18079938
TI  - Confocal enhanced optical coherence tomography for nondestructive evaluation of
      paints and coatings.
AB  - We investigate confocal enhanced optical coherence tomography as a nondestructive
      evaluation tool for imaging with improved image contrast and depth resolution
      through a highly scattering paint layer. The depth responses provided by confocal
      microscopy, optical coherence tomography, and confocal enhanced optical coherence
      tomography for imaging through paint are investigated. We demonstrate that a new
      combination of confocal microscopy and optical coherence tomography provides
      significantly improved resolution and contrast for coherence gated imaging of
      substrate structures under the paint.

PMID- 18079940
TI  - All-fiber coherent beam combining of fiber lasers.
AB  - One half of a 2x2 fused taper single-mode fiber coupler is used for the all-fiber
      spatial and spectral beam combining of two fiber lasers.

PMID- 18079939
TI  - Resonant optical cavity used as a nonradiating source for optical near-field
      microscopy.
AB  - Nonradiating sources are emitting devices whose geometry prohibits
      electromagnetic emission. First, we show that a ring cavity can be substituted
      for the usual prism in scanning tunneling optical microscopy. Second, we find
      that near-field detection is an ideal way to explore the behavior of such
      nonradiating sources.

PMID- 18079941
TI  - Bit-error-rate analysis for a 100-Gbit/s nonlinear optical loop mirror
      demultiplexer employing soliton control and signal pulses.
AB  - On the basis of a previously derived mathematical model, the power penalty
      associated with a nonlinear optical loop mirror (NOLM) demultiplexer was
      calculated, with timing jitter noise, bit-to-bit cross talk, and channel cross
      talk taken into consideration. Simulation results show that a 3-dBm improvement
      in the receiver sensitivity at a bit error rate of 10(-9) can be achieved by
      choice of the appropriate walk-off time between the control and the signal pulses
      within the NOLM demultiplexer.

PMID- 18079942
TI  - Observation of phase conservation in multiwavelength binary phase shift-keying
      pulse-sequence generation at 10 Gbits/s by use of a spectrum-sliced
      supercontinuum in an optical fiber.
AB  - Phase conservation in multiwavelength binary phase shift-keying (BPSK) pulse
      sequence generation by slicing of a supercontinuum spectrum with a dispersion
      flattened normal-dispersion fiber is experimentally observed. A 10-Gbit/s BPSK
      pulse sequence with a bit-error rate of <10(-10) is successfully generated over a
      20-nm-wide wavelength range 1540-1560 nm.

PMID- 18079943
TI  - Temperature-dependent gain and noise in fiber Raman amplifiers.
AB  - An experimental investigation of the temperature dependence of the gain and noise
      performance of a silica-fiber Raman amplifier is described. A decrease in the
      Raman scattering cross section in a fiber amplifier cooled from a temperature of
      300 K to 77 K was measured and found to be in agreement with theoretical values.
      No difference between the Raman gain coefficients at these two temperatures was
      observed.

PMID- 18079944
TI  - Locking in photosensitivity within optical fiber and planar waveguides by
      ultraviolet preexposure.
AB  - Strong photosensitivity is locked in permanently after hydrogen outdiffusion of
      hydrogen-loaded waveguides presensitized with UV light by either pulsed 193-nm or
      cw 244-nm laser output.

PMID- 18079945
TI  - Visualizing the whispering gallery modes in a cylindrical optical microcavity.
AB  - Whispering gallery modes in cylindrical integrated optics microcavities have, for
      what is to our knowledge the first time, been mapped with a photon scanning
      tunneling microscope. Optical images were obtained with a spatial resolution of
      50 nm. By combination of information on the spatial optical distributions with
      wavelength-dependent measurements, an unexpectedly rich variety of intracavity
      phenomena, such as polarization conversion and interference of copropagating and
      counterpropagating modes, could be directly observed. A quantitative comparison
      of the experimental data with computer simulations results in a comprehensive
      understanding of the various whispering gallery modes inside the microcavity.

PMID- 18079946
TI  - Single-molecule detection with a two-photon fluorescence microscope with fast
      scanning capabilities and polarization sensitivity.
AB  - We describe a laser-scanning two-photon fluorescence microscope that is capable
      of observing single molecules with excellent temporal resolution and three
      dimensional spatial resolution. To demonstrate the capabilities of the instrument
      we present single-molecule fluorescence data obtained in several different
      scanning modes. In addition, a polarization-sensitive detection scheme can
      provide detailed three-dimensional information about the orientations of
      molecules in any of these scanning modes.

PMID- 18079947
TI  - High-resolution spectrometry for diffuse light by use of anamorphic
      concentration.
AB  - A new scheme to improve the spectral resolution of grating-based spectrometers
      for diffuse light is proposed and demonstrated. It exploits an anamorphic
      transformation that reduces the beam divergence in the direction of the grating
      grooves while increasing the divergence in the orthogonal direction to improve
      the spectral resolution without any loss of light. Up to 12-fold improvement in
      the spectral resolution was obtained.

PMID- 18079948
TI  - Optical phase locking in the microradian domain: potential applications to NASA
      spaceborne optical measurements.
AB  - We have constructed and demonstrated a high-performance optical phase-locked loop
      between two cw Nd:YAG lasers. The feedback system is relatively simple, employing
      only the laser's internal piezoelectric transducer and an external acousto-optic
      modulator. A residual phase noise of the order of 1microrad between two optical
      fields is achieved in the locked condition, as is verified by time- and frequency
      domain analyses by the two-oscillator approach that is conventionally used in rf
      measurement. Potential applications to NASA space-based optical measurements are
      discussed.

PMID- 18079949
TI  - Fourier-transform infrared imaging using a rapid-scan spectrometer.
AB  - We present a major improvement to the Fourier-transform infrared (FTIR) imaging
      technique brought about by replacement of the commonly used step-scan
      spectrometer with a rapid-scanning spectrometer. This advancement dramatically
      decreases the time required for data collection without decreasing the data
      quality. With this new instrumental setup, an imaging data set consisting of
      64x64 spectra with a 4-cm (-1) spectral resolution over a 1360-cm (-1) spectral
      range can be collected in 34 s. As a practical example, we demonstrate what we
      believe to be the first application of FTIR imaging to the screening of
      adsorbates on the elements of a combinatorial library containing different
      supported catalyst materials in the same reactant feed.

PMID- 18079950
TI  - Kilohertz linewidth from frequency-stabilized mid-infrared quantum cascade
      lasers.
AB  - Frequency stabilization of mid-IR quantum cascade (QC) lasers to the kilohertz
      level has been accomplished by use of electronic servo techniques. With this
      active feedback, an 8.5-microm QC distributed-feedback laser is locked to the
      side of a rovibrational resonance of nitrous oxide (N(2) O) at 1176.61cm (-1) . A
      stabilized frequency-noise spectral density of 42Hz/ radicalHz has been measured
      at 100 kHz; the calculated laser linewidth is 12 kHz.

PMID- 18079951
TI  - From amplified spontaneous emission to laser oscillation: dynamics in a short
      cavity polymer laser.
AB  - We present an experimental study of the input-output characteristics of an
      ultrashort pumped pi -conjugated polymer in solution. By comparing the results
      for configurations with zero, one, and two mirrors around the polymer, we show
      that the physics is driven by amplified spontaneous emission and not by
      cooperative emission. This finding is substantiated by picosecond-time-scale
      measurements of the evolution of the emission of the polymer. For the two-mirror
      configuration a sharply defined threshold for laser oscillation is found; the
      output of the laser exhibits strong pulsations.

PMID- 18079953
TI  - Photorefractive polymeric optical spatial solitons.
AB  - We predict the formation of optical spatial solitons in photorefractive polymers.
      The orientational enhancement from the doped chromophores and the dependency of
      the quantum efficiency of generating mobile holes on the electric field make the
      polymeric solitons behave differently from other photorefractive solitons.

PMID- 18079952
TI  - Observation of a nonlinear mode in a cylindrical Fabry-Perot cavity.
AB  - We report what is believed to be the first observation of a nonlinear mode in a
      cylindrical nonlinear Fabry-Perot cavity. The field enhancement from cavity
      buildup, as well as the large chi((3)) optical nonlinearity that is due to
      resonantly excited (85)Rb vapor, allows the nonlinear mode to form at low
      incident optical powers of less than 1 mW. The mode is observed to occur for both
      self-focusing and self-defocusing nonlinearity.

PMID- 18079954
TI  - Phase-coherent optical frequency division by 3 of 532-nm laser light with a
      continuous-wave optical parametric oscillator.
AB  - Phase-locked 3:1 division of an optical frequency was achieved with a continuous
      wave monolithic optical parametric oscillator (OPO) pumped by a 532-nm Nd:YAG
      laser, by use of 5% MgO-doped LiNbO(3) as a nonlinear optical crystal. The OPO
      generated signal light (798 nm) with 4-mW power and idler light (1596 nm) with 3
      mW power for a pump power of 68 mW. Approximately 2microW of second harmonics
      (SH's) of the idler light was produced by external-cavity-enhanced SH generation
      by use of a periodically poled LiNbO(3) crystal. The beat signal between the
      signal light and the SH of the idler light was observed with a signal-to-noise
      ratio of 40 dB at a 10-kHz bandwidth and was successfully phase locked to a
      signal from a synthesizer through the electro-optic effect of the crystal.

PMID- 18079955
TI  - Solitons and collapse suppression due to parametric interaction in bulk Kerr
      media.
AB  - We demonstrate that weak parametric interaction of a fundamental beam with its
      harmonic field in a Kerr medium can drastically modify the beam dynamics, giving
      rise to very complex bifurcation phenomena and quasi solitons. Most importantly,
      we reveal a novel physical mechanism of the collapse suppression in a bulk
      optical Kerr medium: parametric coupling to a weakly radiating harmonic field.

PMID- 18079956
TI  - Highly sensitive self-mixing measurement of Brillouin scattering with a laser
      diode-pumped microchip LiNdP(4)O(12) laser.
AB  - Brillouin scattering has been measured with a high degree of sensitivity by a
      system built around a laser-diode-pumped microchip LiNdP(4)O(12) laser. An
      efficient self-mixing modulation effect that is due to the interference between a
      lasing field and a weak field fed back from an acousto-optic modulator by means
      of a phase-conjugate reflection was used. Laser-Doppler velocimetry that can
      discriminate the direction of motion has been demonstrated.

PMID- 18079957
TI  - Optical alignment of azo-polymer-stabilized nematic liquid crystals.
AB  - Optical alignment and strong residual birefringence in a nematic liquid crystal
      that is stabilized by a polymer network are described. The polymer's main chain
      contains an azo dye, which is responsible for the repulsion of the axis of the
      guest-host system from the electric field of the excitation light.

PMID- 18079958
TI  - Measurement of pulse asymmetry by three-photon-absorption autocorrelation in a
      GaAsP photodiode.
AB  - Three-photon absorption in a GaAsP photodiode is used for what is believed to be
      the first time for nonlinear optical autocorrelation at wavelengths from 1.4 to
      1.6microm . Theoretical intensity dependence and contrast ratios are achieved,
      and the ratio of the three- to the two-photon-absorption coefficient is measured.
      Finally, it is demonstrated that pulse asymmetry can be measured with no
      direction-of-time ambiguity by use of unbalanced three-photon-absorption
      autocorrelation.

PMID- 18079959
TI  - Symmetries, chirp-free points, and bistability in dispersion-managed fiber lines.
AB  - We show from an elementary symmetry analysis that, in dispersion-compensated
      systems for which a lossless model is valid, nonlinearity requires a chirp-free
      point at the center of symmetry (if such exists) of the map for any kind of
      unique periodic solution. We also present an example of a more-complex map when
      the periodic solution is not unique.

PMID- 18079960
TI  - Efficient femtosecond traveling-wave optical parametric amplification in
      periodically poled KTiOPO(4).
AB  - We report, for the first time to our knowledge, high-power femtosecond traveling
      wave optical parametric amplification by use of periodically poled KTiOPO(4) .
      With a single pass through a 4-mm-long sample of 1.23-mm thickness we achieved
      40% internal conversion efficiency and 5microJ of single-pulse idler energy near
      3.8microm , using only 75microJ of energy from the output of a conventional 1-kHz
      Ti:sapphire regenerative amplifier. The 210-fs-long idler pulses were almost
      transform limited. We discuss the specific problems encountered in high-power
      parametric conversion, such as unwanted quasi-phase-matched upconversion
      processes for polarization configurations that utilize the largest (d(33))
      nonlinear coefficient and the related formation of color centers (gray tracking)
      in KTiOPO(4) .

PMID- 18079961
TI  - Fourier-transform sum-frequency surface vibrational spectroscopy with femtosecond
      pulses.
AB  - We present a Fourier-transform spectroscopic technique for investigation of
      surfaces and interfaces based on IR-visible sum-frequency generation with
      femtosecond light pulses. The observed spectrum has a resolution that is
      independent of the input pulse characteristics.

PMID- 18079962
TI  - TRAIL-R deficiency in mice promotes susceptibility to chronic inflammation and
      tumorigenesis.
AB  - Preclinical data support the potential of the death-signaling receptors for TRAIL
      as targets for cancer therapy. However, it is unclear whether these death
      signaling receptors suppress the emergence and growth of malignant tumors in
      vivo. Herein we show that TNF-related apoptosis-inducing ligand receptor (TRAIL
      R), the only proapoptotic death-signaling receptor for TRAIL in the mouse,
      suppresses inflammation and tumorigenesis. Loss of a single TRAIL-R allele on the
      lymphoma-prone Emu-myc genetic background significantly reduced median lymphoma
      free survival. TRAIL-R-deficient lymphomas developed with equal frequency
      irrespective of mono- or biallelic loss of TRAIL-R, had increased metastatic
      potential, and showed apoptotic defects relative to WT littermates. In addition,
      TRAIL-R-/- mice showed decreased long-term survival following a sublethal dose of
      ionizing radiation. Histological evaluation of moribund irradiated TRAIL-R-/-
      animals showed hallmarks of bronchopneumonia as well as tumor formation with
      increased NF-kappaB p65 expression. TRAIL-R also suppressed diethylnitrosamine
      induced (DEN-induced) hepatocarcinogenesis, as an increased number of large
      tumors with apoptotic defects developed in the livers of DEN-treated TRAIL-R-/-
      mice. Thus TRAIL-R may function as an inflammation and tumor suppressor in
      multiple tissues in vivo.

PMID- 18079963
TI  - Suppression of renal cell carcinoma growth by inhibition of Notch signaling in
      vitro and in vivo.
AB  - Loss of the tumor suppressor gene von Hippel-Lindau (VHL) plays a key role in the
      oncogenesis of clear cell renal cell carcinoma (CCRCC). The loss leads to
      stabilization of the HIF transcription complex, which induces angiogenic and
      mitogenic pathways essential for tumor formation. Nonetheless, additional
      oncogenic events have been postulated to be required for the formation of CCRCC
      tumors. Here, we show that the Notch signaling cascade is constitutively active
      in human CCRCC cell lines independently of the VHL/HIF pathway. Blocking Notch
      signaling resulted in attenuation of proliferation and restrained anchorage
      independent growth of CCRCC cell lines. Using siRNA targeting the different Notch
      receptors established that the growth-promoting effects of the Notch signaling
      pathway were attributable to Notch-1 and that Notch-1 knockdown was accompanied
      by elevated levels of the negative cell-cycle regulators p21 Cip1 and/or p27
      Kip1. Treatment of nude mice with an inhibitor of Notch signaling potently
      inhibited growth of xenotransplanted CCRCC cells. Moreover, Notch-1 and the Notch
      ligand Jagged-1 were expressed at significantly higher levels in CCRCC tumors
      than in normal human renal tissue, and the growth of primary CCRCC cells was
      attenuated upon inhibition of Notch signaling. These findings indicate that the
      Notch cascade may represent a novel and therapeutically accessible pathway in
      CCRCC.

PMID- 18079964
TI  - Immunostimulatory Tim-1-specific antibody deprograms Tregs and prevents
      transplant tolerance in mice.
AB  - T cell Ig mucin (Tim) molecules modulate CD4(+) T cell responses. In keeping with
      the view that Tim-1 generates a stimulatory signal for CD4(+) T cell activation,
      we hypothesized that an agonist Tim-1-specific mAb would intensify the CD4(+) T
      cell-dependant allograft response. Unexpectedly, we determined that a particular
      Tim-1-specific mAb exerted reciprocal effects upon the commitment of
      alloactivated T cells to regulatory and effector phenotypes. Commitment to the
      Th1 and Th17 phenotypes was fostered, whereas commitment to the Treg phenotype
      was hindered. Moreover, ligation of Tim-1 in vitro effectively deprogrammed Tregs
      and thus produced Tregs unable to control T cell responses. Overall, the effects
      of the agonist Tim-1-specific mAb on the allograft response stemmed from enhanced
      expansion and survival of T effector cells; a capacity to deprogram natural
      Tregs; and inhibition of the conversion of naive CD4(+) T cells into Tregs. The
      reciprocal effects of agonist Tim-1-specific mAbs upon effector T cells and Tregs
      serve to prevent allogeneic transplant tolerance.

PMID- 18079965
TI  - Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its
      ligands in apoE-/- mice.
AB  - Endothelial dysfunction is a key triggering event in atherosclerosis. Following
      the entry of lipoproteins into the vessel wall, their rapid modification results
      in the generation of advanced glycation endproduct epitopes and subsequent
      infiltration of inflammatory cells. These inflammatory cells release receptor for
      advanced glycation endproduct (RAGE) ligands, specifically S100/calgranulins and
      high-mobility group box 1, which sustain vascular injury. Here, we demonstrate
      critical roles for RAGE and its ligands in vascular inflammation, endothelial
      dysfunction, and atherosclerotic plaque development in a mouse model of
      atherosclerosis, apoE-/- mice. Experiments in primary aortic endothelial cells
      isolated from mice and in cultured human aortic endothelial cells revealed the
      central role of JNK signaling in transducing the impact of RAGE ligands on
      inflammation. These data highlight unifying mechanisms whereby endothelial RAGE
      and its ligands mediate vascular and inflammatory stresses that culminate in
      atherosclerosis in the vulnerable vessel wall.

PMID- 18079966
TI  - Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3
      pathway in murine models of stroke.
AB  - Secretoneurin (SN), a neuropeptide derived from secretogranin II, promotes
      neurite outgrowth of immature cerebellar granule cells. SN also aids in the
      growth and repair of neuronal tissue, although the precise mechanisms underlying
      the promotion of brain tissue neuroprotection and plasticity by SN are not
      understood. Here, in a rat model of stroke and in ischemic human brain tissue, SN
      was markedly upregulated in both neurons and endothelial cells. SN-mediated
      neuroprotection rescued primary cortical cell cultures from oxygen/glucose
      deprivation. SN also induced expression of the antiapoptotic proteins Bcl-2 and
      Bcl-xL through the Jak2/Stat3 pathway and inhibited apoptosis by blocking caspase
      3 activation. In addition, rats with occluded right middle cerebral arteries
      showed less cerebral infarction, improved motor performance, and increased brain
      metabolic activity following i.v. administration of SN. Furthermore, SN injection
      enhanced stem cell targeting to the injured brain in mice and promoted the
      formation of new blood vessels to increase local cortical blood flow in the
      ischemic hemisphere. Both in vitro and in vivo, SN not only promoted
      neuroprotection, but also enhanced neurogenesis and angiogenesis. Our results
      demonstrate that SN acts directly on neurons after hypoxia and ischemic insult to
      further their survival by activating the Jak2/Stat3 pathway.

PMID- 18079967
TI  - TRAIL-R deficiency in mice enhances lymph node metastasis without affecting
      primary tumor development.
AB  - TRAIL is a promising anticancer agent due to its ability to selectively induce
      apoptosis in established tumor cell lines but not nontransformed cells. Herein,
      we demonstrate a role for the apoptosis-inducing TRAIL receptor (TRAIL-R) as a
      metastasis suppressor. Although mouse models employing tumor transplantation have
      shown that TRAIL can reduce tumor growth, autochthonous tumor models have
      generated conflicting results with respect to the physiological role of the TRAIL
      system during tumorigenesis. We used a multistage model of squamous cell
      carcinoma to examine the role of TRAIL-R throughout all steps of tumor
      development. DMBA/TPA-treated TRAIL-R-deficient mice showed neither an increase
      in number or growth rate of benign papillomas nor an increase in the rate of
      progression to squamous cell carcinoma. However, metastasis to lymph nodes was
      significantly enhanced, indicating a role for TRAIL-R specifically in the
      suppression of metastasis. We also found that adherent TRAIL-R-expressing skin
      carcinoma cells were TRAIL resistant in vitro but were sensitized to TRAIL upon
      detachment by inactivation of the ERK signaling pathway. As detachment from the
      primary tumor is an obligatory step in metastasis, this provides a possible
      mechanism by which TRAIL-R could inhibit metastasis. Hence, treatment of cancer
      patients with agonists of the apoptosis-inducing receptors for TRAIL may prove
      useful in reducing the incidence of metastasis.

PMID- 18079968
TI  - Phospholipase C beta3 deficiency leads to macrophage hypersensitivity to
      apoptotic induction and reduction of atherosclerosis in mice.
AB  - Atherosclerosis is an inflammatory disease that is associated with monocyte
      recruitment and subsequent differentiation into lipid-laden macrophages at sites
      of arterial lesions, leading to the development of atherosclerotic plaques. PLC
      is a key member of signaling pathways initiated by G protein-coupled ligands in
      macrophages. However, the role of this enzyme in the regulation of macrophage
      function is not known. Here, we studied macrophages from mice lacking PLC beta2,
      PLC beta3, or both PLC isoforms and found that PLC beta3 is the major functional
      PLC beta isoform in murine macrophages. Although PLC beta3 deficiency did not
      affect macrophage migration, adhesion, or phagocytosis, it resulted in macrophage
      hypersensitivity to multiple inducers of apoptosis. PLC beta3 appeared to
      regulate this sensitivity via PKC-dependent upregulation of Bcl-XL. The
      significance of PLC beta signaling in vivo was examined using the apoE-deficient
      mouse model of atherosclerosis. Mice lacking both PLC beta3 and apoE exhibited
      fewer total macrophages and increased macrophage apoptosis in atherosclerotic
      lesions, as well as reduced atherosclerotic lesion size when compared with mice
      lacking only apoE. These results demonstrate what we believe to be a novel role
      for PLC activity in promoting macrophage survival in atherosclerotic plaques and
      identify PLC beta3 as a potential target for treatment of atherosclerosis.

PMID- 18079970
TI  - The MEF2D transcription factor mediates stress-dependent cardiac remodeling in
      mice.
AB  - The adult heart responds to excessive neurohumoral signaling and workload by a
      pathological growth response characterized by hypertrophy of cardiomyocytes and
      activation of a fetal program of cardiac gene expression. These responses
      culminate in diminished pump function, ventricular dilatation, wall thinning, and
      fibrosis, and can result in sudden death. Myocyte enhancer factor-2 (MEF2)
      transcription factors serve as targets of the signaling pathways that drive
      pathological cardiac remodeling, but the requirement for MEF2 factors in the
      progression of heart disease in vivo has not been determined. MEF2A and MEF2D are
      the primary MEF2 factors expressed in the adult heart. To specifically determine
      the role of MEF2D in pathological cardiac remodeling, we generated mice with a
      conditional MEF2D allele. MEF2D-null mice were viable, but were resistant to
      cardiac hypertrophy, fetal gene activation, and fibrosis in response to pressure
      overload and beta-chronic adrenergic stimulation. Furthermore, we show in a
      transgenic mouse model that forced overexpression of MEF2D was sufficient to
      drive the fetal gene program and pathological remodeling of the heart. These
      results reveal a unique and important function for MEF2D in stress-dependent
      cardiac growth and reprogramming of gene expression in the adult heart.

PMID- 18079971
TI  - Athletic Involvement and Adolescent Delinquency.
AB  - Athough conventional wisdom suggests that organized sport deters delinquency by
      building character, structuring adolescents' time, and providing incentives for
      socially approved behavior, the empirical evidence to date has been mixed. Based
      on a sample of approximately 600 Western New York adolescents, the present study
      examined how self-reported jock identity, school athlete status, and frequency of
      athletic activity differentially influenced a range of delinquent behaviors.
      Neither athlete status nor frequency of athletic activity predicted these
      behaviors; however, jock identity was associated with significantly more
      incidents of delinquency. This finding was robust across both gender and race.
      Follow-up analyses indicated that jock identity facilitated both minor and major
      delinquency, with major delinquency effects for white but not black adolescents.

PMID- 18079969
TI  - The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis
      and metastatic progression in mice by amplifying ErbB2 signaling.
AB  - Overexpression of the receptor tyrosine kinase EPH receptor A2 (EphA2) is
      commonly observed in aggressive breast cancer and correlates with a poor
      prognosis. However, while EphA2 has been reported to enhance tumorigenesis,
      proliferation, and MAPK activation in several model systems, other studies
      suggest that EphA2 activation diminishes these processes and inhibits the
      activity of MAPK upon ligand stimulation. In this study, we eliminated EphA2
      expression in 2 transgenic mouse models of mammary carcinoma. EphA2 deficiency
      impaired tumor initiation and metastatic progression in mice overexpressing ErbB2
      (also known as Neu) in the mammary epithelium (MMTV-Neu mice), but not in mice
      overexpressing the polyomavirus middle T antigen in mammary epithelium (MMTV-PyV
      mT mice). Histologic and ex vivo analyses of MMTV-Neu mouse mammary epithelium
      indicated that EphA2 enhanced tumor proliferation and motility. Biochemical
      analyses revealed that EphA2 formed a complex with ErbB2 in human and murine
      breast carcinoma cells, resulting in enhanced activation of Ras-MAPK signaling
      and RhoA GTPase. Additionally, MMTV-Neu, but not MMTV-PyV-mT, tumors were
      sensitive to therapeutic inhibition of EphA2. These data suggest that EphA2
      cooperates with ErbB2 to promote tumor progression in mice and may provide a
      novel therapeutic target for ErbB2-dependent tumors in humans. Moreover, EphA2
      function in tumor progression appeared to depend on oncogene context, an
      important consideration for the application of therapies targeting EphA2.

PMID- 18079973
TI  - Intrathecal polymer-based interleukin-10 gene delivery for neuropathic pain.
AB  - Research on communication between glia and neurons has increased in the past
      decade. The onset of neuropathic pain, a major clinical problem that is not
      resolved by available therapeutics, involves activation of spinal cord glia
      through the release of proinflammatory cytokines in acute animal models of
      neuropathic pain. Here, we demonstrate for the first time that the spinal action
      of the proinflammatory cytokine, interleukin 1 (IL-1) is involved in maintaining
      persistent (2 months) allodynia induced by chronic-constriction injury (CCI). The
      anti-inflammatory cytokine IL-10 can suppress proinflammatory cytokines and
      spinal cord glial amplification of pain. Given that IL-1 is a key mediator of
      neuropathic pain, developing a clinically viable means of long-term delivery of
      IL-10 to the spinal cord is desirable. High doses of intrathecal IL-10-gene
      therapy using naked plasmid DNA (free pDNA-IL-10) is effective, but the dose
      required limits its potential clinical utility. Here we show that intrathecal
      gene therapy for neuropathic pain is improved sufficiently using two, distinct
      synthetic polymers, poly(lactic-co-glycolic) and polyethylenimine, that
      substantially lower doses of pDNA-IL-10 are effective. In conclusion, synthetic
      polymers used as i.t. gene-delivery systems are well-tolerated and improve the
      long-duration efficacy of pDNA-IL-10 gene therapy.

PMID- 18079975
TI  - Microwave-Enhanced Fluorous Synthesis.
AB  - A new technology for high-speed solution-phase parallel synthesis has been
      developed by the combination of microwave heating and fluorous tagging
      strategies. This article highlights several applications of this technology in
      the synthesis of library scaffolds involving Pd-catalyzed cross-coupling and
      multicomponent reactions.

PMID- 18079974
TI  - Investigation of miRNA biology by bioinformatic tools and impact of miRNAs in
      colorectal cancer--regulatory relationship of c-Myc and p53 with miRNAs.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate gene
      expression at the posttranscriptional and translational levels and have been
      demonstrated to be involved in diverse biological functions. Mounting evidence in
      recent years has shown that miRNAs play key roles in tumorigenesis due to
      abnormal expression of and mutations in miRNAs. High throughput miRNA expression
      profiling of several major tumor types has identified miRNAs associated with
      clinical diagnosis and prognosis of cancer treatment. Previously our group has
      discovered a novel regulatory relationship between tumor suppressor gene p53 with
      miRNAs expression and a number of miRNA promoters contain putative p53 binding
      sites. In addition, others have reported that c-myc can mediate a large number of
      miRNAs expression. In this review, we will emphasize algorithms to identify mRNA
      targets of miRNAs and the roles of miRNAs in colorectal cancer. In particular, we
      will discuss a novel regulatory relationship of miRNAs with tumor suppressor p53
      and c-myc. miRNAs are becoming promising novel targets and biomarkers for future
      cancer therapeutic development and clinical molecular diagnosis.

PMID- 18079976
TI  - Molecular Phylogeny of Neotropical Anopheles (Nyssorhynchus) Albitarsis Species
      Complex (Diptera: Culicidae).
AB  - A phylogeny was reconstructed for four species belonging to the Neotropical
      Anopheles (Nyssorhynchus) albitarsis complex using partial sequences from the
      mitochondrial cytochrome oxidase I (COI) and NADH dehydrogenase 4 (ND4) genes and
      the ribosomal DNA ITS2 and D2 expansion region of the 28S subunit. The basis for
      initial characterization of each member of the complex was by correlated random
      amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR) markers.
      Analyses were carried out with and without an outgroup (An.(Nys.) argyritarsis
      Robineau-Desvoidy) by using maximum parsimony, maximum likelihood, and Bayesian
      methods. A total evidence approach without the outgroup, using separate models
      for "fast" (COI and ND4 position 3) and "slow" (rDNA ITS2 and D2, and COI and ND4
      position 1) partitions, gave the best supported topology, showing close
      relationships of An. albitarsis Lynch-Arribalzaga to An. albitarsis B and An.
      marajoara Galvao & Damasceno to An. deaneorum Rosa-Freitas. Analyses with the
      outgroup included showed poorer support, possibly because of a long branch
      attraction effect caused by a divergent outgroup, which caused one of the An.
      marajoara specimens to cluster with An. deaneorum in some analyses. The
      relationship of the above-mentioned result to a separately proposed hypothesis
      suggesting a fifth species in the complex is discussed.

PMID- 18079978
TI  - Relative threat and recognition ability in the responses of tropical mockingbirds
      to song playback.
AB  - It has been suggested that individual recognition based on song may be
      constrained by repertoire size in songbirds with very large song repertoires.
      This hypothesis has been difficult to test because there are few studies on
      species with very large repertoires and because traditional experiments based on
      the dear enemy effect do not provide evidence against recognition. The tropical
      mockingbird, Mimus gilvus, is a cooperative breeder with very large song
      repertoires and stable territorial neighbourhoods. The social system of this
      species allowed us to test individual recognition based on song independently
      from the dear enemy effect by evaluating male response to playback of strangers,
      neighbours (from shared and unshared boundaries), co-males (i.e. other males in
      the same social group) and own songs. Although subjects did not show a dear enemy
      effect, they were less aggressive to co-males than to all other singers. Our
      results suggest that recognition in tropical mockingbirds (1) does not simply
      distinguish between familiar and unfamiliar singers, (2) requires a small sample
      of both songs and song types, (3) does not rely on individual-specific sequences
      of song types and (4) is not likely to rely on group-specific vocal signatures
      potentially available in cooperatively breeding groups. We conclude that this is
      a case of true recognition and suggest that the lack of a dear enemy effect in
      this and other species with large repertoires may relate to the role of song in
      mate attraction and the perception of neighbours as a threat to future paternity.

PMID- 18079979
TI  - Shape-dependent designability studies of lattice proteins.
AB  - One important problem in computational structural biology is protein
      designability, that is, why protein sequences are not random strings of amino
      acids but instead show regular patterns that encode protein structures. Many
      previous studies that have attempted to solve the problem have relied upon
      reduced models of proteins. In particular, the 2D square and the 3D cubic
      lattices together with reduced amino acid alphabet models have been examined
      extensively and have lead to interesting results that shed some light on
      evolutionary relationship among proteins. Here we perform designability studies
      on the 2D square lattice and explore the effects of variable overall shapes on
      protein designability using a binary hydrophobic-polar (HP) amino acid alphabet.
      Because we rely on a simple energy function that counts the total number of H-H
      interactions between non-sequential residues, we restrict our studies to protein
      shapes that have the same number of residues and also a constant number of non
      bonded contacts. We have found that there is a marked difference in the
      designability between various protein shapes, with some of them accounting for a
      significantly larger share of the total foldable sequences.

PMID- 18079980
TI  - Color-object interference in young children: A Stroop effect in children 31/2
      61/2 years old.
AB  - The Stroop color-word task cannot be administered to children who are unable to
      read. However, our color-object Stroop task can. One hundred and sixty-eight
      children of 31/2-61/2 years (50% female; 24 children at each 6-month interval)
      were shown line drawings of familiar objects in a color that was congruent (e.g.,
      an orange carrot), incongruent (e.g., a green carrot), or neutral (for objects
      having no canonical color [e.g., a red book]), and abstract shapes, each drawn in
      one of six colors. Half the children were asked to name the color in which each
      object was drawn, and half were to name each object. Children's predominant
      tendency was to say what the object was; when instructed to do otherwise they
      were slower and less accurate. Children were faster and more accurate at naming
      the color of a stimulus when the form could not be named (abstract shape) than
      when it could, even if in its canonical color. The heightened interference to
      color-naming versus object-naming was not due to lack of familiarity with color
      names or group differences: Children in the color condition were as fast and
      accurate at naming the colors of abstract shapes as were children in the form
      condition at naming familiar objects.

PMID- 18079981
TI  - Microwave Ablation With a Triaxial Antenna: Results in ex vivo Bovine Liver.
AB  - We apply a new triaxial antenna for microwave ablation procedures to an ex vivo
      bovine liver. The antenna consists of a coaxial monopole inserted through a
      biopsy needle positioned one quarter-wavelength from the antenna base. The
      insertion needle creates a triaxial structure, which enhances return loss more
      than 10 dB, maximizing energy transfer to the tissue while minimizing feed cable
      heating and invasiveness. Numerical electromagnetic and thermal simulations are
      used to optimize the antenna design and predict heating patterns. Numerical and
      ex vivo experimental results show that the lesion size depends strongly on
      ablation time and average input power, but not on peak power. Pulsing algorithms
      are also explored. We were able to measure a 3.8-cm lesion using 50 W for 7 min,
      which we believe to be the largest lesion reported thus far using a 17-gauge
      insertion needle.

PMID- 18079982
TI  - Analysis and experimental validation of a triaxial antenna for microwave tumor
      ablation.
AB  - We apply a new triaxial antenna for microwave ablation procedures. The antenna
      consists of a coaxial monopole inserted through an 18-gauge biopsy needle
      positioned one quarter-wavelength from the antenna base. The biopsy needle
      creates a triaxial structure, which enhances return loss by more than 10 dB, thus
      limiting return currents along the feed line. Numerical simulations are used to
      optimize the antenna design. Numerical and ex-vivo experimental results are
      presented to quantify the field distribution, heating pattern and return loss of
      the antenna.

PMID- 18079983
TI  - Cesium fluoride and tetra-n-butylammonium fluoride mediated 1,4-N-->O shift of
      disubstituted phenyl ring of a bicalutamide derivative.
AB  - A novel 1,4-N-->O migration of a disubstituted phenyl ring was observed during N
      methylation of a bicalutamide derivative, (2S)-2-(tert-butyldimethylsilanyloxy)-N
      (4-cyano-3-trifluoromethylphenyl)-3-(4-fluorophenoxy)-2-methylpropionamide, in
      the presence of CsF-Celite/acetonitrile and desilylation of (2S)-2-(tert
      butyldimethylsilanyloxy)-N-(4-cyano-3-trifluoromethylphenyl)-3-(4-fluorophenoxy)
      2,N-dimethylpropionamide in tetra-n-butylammonium fluoride/THF. Both NMR and X
      ray analysis confirmed the structure of the 1,4-N-->O disubstituted phenyl ring
      migrated product.

PMID- 18079985
TI  - Understanding the dynamic behavior of genetic regulatory networks by functional
      decomposition.
AB  - A number of mechanistic and predictive genetic regulatory networks (GRNs)
      comprising dozens of genes have already been characterized at the level of cis
      regulatory interactions. Reconstructions of networks of 100's to 1000's of genes
      and their interactions are currently underway. Understanding the organizational
      and functional principles underlying these networks is probably the single
      greatest challenge facing genomics today. We review the current approaches to
      deciphering large-scale GRNs and discuss some of their limitations. We then
      propose a bottom-up approach in which large-scale GRNs are first organized in
      terms of functionally distinct GRN building blocks of one or a few genes.
      Biological processes may then be viewed as the outcome of functional interactions
      among these simple, well-characterized functional building blocks. We describe
      several putative GRN functional building blocks and show that they can be located
      within GRNs on the basis of their interaction topology and additional, simple and
      experimentally testable constraints.

PMID- 18079986
TI  - Synthesis of irreversibly binding bicalutamide analogs for imaging studies.
AB  - A new synthetic methodology for preparing radioactive androgen receptor binding
      compounds in order to determine receptor-ligands interactions has been developed.

PMID- 18079987
TI  - Synthesis of oxazolidinedione derived bicalutamide analogs.
AB  - The synthesis of chiral oxazolidinedione derived bicalutamide analogs has been
      discussed.

PMID- 18079988
TI  - Prognostic Values of microRNAs in Colorectal Cancer.
AB  - The functions of non-coding microRNAs (miRNAs) in tumorigenesis are just
      beginning to emerge. Previous studies from our laboratory have identified a
      number of miRNAs that were deregulated in colon cancer cell lines due to the
      deletion of the p53 tumor suppressor gene. In this study, the in vivo
      significance of some of these miRNAs was further evaluated using colorectal
      clinical samples. Ten miRNAs (hsa-let-7b, hsa-let-7g, hsa-miR-15b, hsa-miR-181b,
      hsa-miR-191, hsa-miR-200c, hsa-miR-26a, hsa-miR-27a, hsa-miR-30a-5p and hsa-miR
      30c) were evaluated for their potential prognostic value in colorectal cancer
      patients. Forty eight snap frozen clinical colorectal samples (24 colorectal
      cancer and 24 paired normal patient samples) with detailed clinical follow-up
      information were selected. The expression levels of 10 miRNAs were quantified via
      qRT-PCR analysis. The statistical significance of these markers for disease
      prognosis was evaluated using a two tailed paired Wilcoxon test. A Kaplan-Meier
      survival curve was generated followed by performing a Logrank test. Among the ten
      miRNAs, hsa-miR-15b (p = 0.0278), hsa-miR-181b (p = 0.0002), hsa-miR-191 (p =
      0.0264) and hsa-miR-200c (p = 0.0017) were significantly over-expressed in tumors
      compared to normal colorectal samples. Kaplan-Meier survival analysis indicated
      that hsa-miR-200c was significantly associated with patient survival (p =
      0.0122). The patients (n = 15) with higher hsa-miR-200c expression had a shorter
      survival time (median survival = 26 months) compared to patients (n = 9) with
      lower expression (median survival = 38 months). Sequencing analysis revealed that
      hsa-miR-181b (p = 0.0098) and hsa-miR-200c (p = 0.0322) expression were strongly
      associated with the mutation status of the p53 tumor suppressor gene. Some of
      these miRNAs may function as oncogenes due to their over-expression in tumors.
      hsa-miR-200c may be a potential novel prognostic factor in colorectal cancer.

PMID- 18079989
TI  - Photochemical Schiemann Reaction in Ionic Liquids.
AB  - Photochemical Schiemann reactions of imidazole derivatives 1 and 4 were carried
      out in 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid [bmim][BF(4)]
      as solvent. The effects of temperature, co-solvent and wavelength on the rate of
      the reaction and product yield were examined. The use of ionic liquid increases
      the yield of the photochemical fluorodediazoniation reaction of 2 at 0 degrees C.
      Careful temperature control is necessary to minimize the photodecomposition of
      the ionic liquid in order to increase the yield of product.

PMID- 18079990
TI  - Crack Cocaine Injection Practices and HIV Risk: Findings From New York and
      Bridgeport.
AB  - This article examines the behavioral practices and health risks associated with
      preparing crack cocaine for injection. Using an ethno-epidemiological approach,
      injection drug users (n=38) were recruited between 1999 and 2000 from public
      settings in New York City and Bridgeport, Connecticut and responded to a
      semistructured interview focusing on crack injection initiation and their most
      recent crack injection. Study findings indicate that methods of preparing crack
      for injection were impacted by a transforming agent, heat applied to the
      "cooker," heroin use, age of the injector, and geographic location of the
      injector. The findings suggest that crack injectors use a variety of methods to
      prepare crack, which may carry different risks for the transmission of bloodborne
      pathogens. In particular, crack injection may be an important factor in the
      current HIV epidemic.

PMID- 18079992
TI  - Brain Mechanisms for Interpreting the Actions of Others From Biological-Motion
      Cues.
AB  - Humans are an intensely social species. Our social abilities depend upon
      specialized brain systems for rapidly recognizing the faces of others, for
      interpreting the actions of others through an analysis of biological-motion cues,
      and for determining the emotional states of others via inspection of facial
      expression. Recent work has implicated the superior temporal sulcus (STS) region
      as an important component of the social brain. Functional neuroimaging studies
      have provided clues about how this region is involved in the visual analysis and
      interpretation of other people's actions. STS activity is modulated by the
      context within which the actions of biological entities are observed. Such a
      contextual influence is consistent with a broader tradition within social
      psychology emphasizing the powerful influences of situational and contextual
      factors on behavior and perception. The STS region also shows promise as a region
      of importance in the investigation of both typical and impaired social-cognitive
      development. Future work should aim to inform us better of the development of
      interrelationships between the STS region and other regions of the social brain,
      including the amygdala and the fusiform gyrus.

PMID- 18079991
TI  - Effects of cytokines and infections on brain neurochemistry.
AB  - Administration of cytokines to animals can elicit many effects on the brain,
      particularly neuroendocrine and behavioral effects. Cytokine administration also
      alters neurotransmission, which may underlie these effects. The most well studied
      effect is the activation of the hypothalamo-pituitary-adrenocortical (HPA) axis,
      especially that by interleukin-1 (IL-1). Peripheral and central administration of
      IL-1 also induces norepinephrine (NE) release in the brain, most markedly in the
      hypothalamus. Small changes in brain dopamine (DA) are occasionally observed, but
      these effects are not regionally selective. IL-1 also increases brain
      concentrations of tryptophan, and the metabolism of serotonin (5-HT) throughout
      the brain in a regionally nonselective manner. Increases of tryptophan and 5-HT,
      but not NE, are also elicited by IL-6, which also activates the HPA axis,
      although it is much less potent in these respects than IL-1. IL-2 has modest
      effects on DA, NE and 5-HT. Like IL-6, tumor necrosis factor-alpha (TNFalpha)
      activates the HPA axis, but affects NE and tryptophan only at high doses. The
      interferons (IFN's) induce fever and HPA axis activation in man, but such effects
      are weak or absent in rodents. The reported effects of IFN's on brain
      catecholamines and serotonin have been very varied. However, interferon-gamma,
      and to a lesser extent, interferon-alpha, have profound effects on the catabolism
      of tryptophan, effectively reducing its concentration in plasma, and may thus
      limit brain 5-HT synthesis.Administration of endotoxin (LPS) elicits responses
      similar to those of IL-1. Bacterial and viral infections induce HPA activation,
      and also increase brain NE and 5-HT metabolism and brain tryptophan. Typically,
      there is also behavioral depression. These effects are strikingly similar to
      those of IL-1, suggesting that IL-1 secretion, which accompanies many infections,
      may mediate these responses. Studies with IL-1 antagonists, support this
      possibility, although in most cases the antagonism is incomplete, suggesting the
      existence of multiple mechanisms. Because LPS is known to stimulate the secretion
      of IL-1, IL-6 and TNFalpha, it seems likely that these cytokines mediate at least
      some of the responses, but studies with antagonists indicate that there are
      multiple mechanisms. The neurochemical responses to cytokines are likely to
      underlie the endocrine and behavioral responses. The NE response to IL-1 appears
      to be instrumental in the HPA activation, but other mechanisms exist. Neither the
      noradrenergic nor the serotonergic systems appear to be involved in the major
      behavioral responses. The significance of the serotonin response is unknown.

PMID- 18079993
TI  - Resilience Among Young Men Who Have Sex With Men in New York City.
AB  - This article describes a study of resilience among young men who have sex with
      men (YMSM). Resilience is defined as positive adaptation in the context of
      hardship. Using targeted sampling to capture the diversity and range of this
      hidden population, we recruited 569 YMSM ages 17-28 years old and examined a
      subset of 134 YMSM who had experienced severe childhood adversity, as indicated
      by placement in foster care. Most of the YMSM in this subset were from racial or
      ethnic minority backgrounds and fewer than half identified as gay or homosexual
      (46.3 percent). More than half (58.3 percent) exhibited positive outcomes on four
      of seven indicators of adaptive functioning. YMSM who identified as either
      bisexual or heterosexual exhibited lower rates of resilience. Structural- as well
      as individual-level factors appear to be implicated in resilience among YMSM.
      Findings underscore the importance of fostering stable sexual identity as a means
      of building resilience.

PMID- 18079994
TI  - The development of an Arabidopsis model system for genome-wide analysis of
      polyploidy effects.
AB  - Arabidopsis is a model system not only for studying numerous aspects of plant
      biology, but also for understanding mechanisms of the rapid evolutionary process
      associated with genome duplication and polyploidization. Although in animals
      interspecific hybrids are often sterile and aneuploids are related to disease
      syndromes, both Arabidopsis autopolyploids and allopolyploids occur in nature and
      can be readily formed in the laboratory, providing an attractive system for
      comparing changes in gene expression and genome structure among relatively
      'young' and 'established' or 'ancient' polyploids. Powerful reverse and forward
      genetics in Arabidopsis offer an exceptional means by which regulatory mechanisms
      of gene and genome duplication may be revealed. Moreover, the Arabidopsis genome
      is completely sequenced; both coding and non-coding sequences are available. We
      have developed spotted oligo-gene and chromosome microarrays using the complete
      Arabidopsis genome sequence. The oligo-gene microarray consists of ~26 000 70-mer
      oligonucleotides that are designed from all annotated genes in Arabidopsis, and
      the chromosome microarray contains 1 kb genomic tiling fragments amplified from a
      chromosomal region or the complete sequence of chromosome 4. We have demonstrated
      the utility of microarrays for genome-wide analysis of changes in gene
      expression, genome organization and chromatin structure in Arabidopsis polyploids
      and related species.

PMID- 18079996
TI  - Macrophage migration inhibitory factor in pediatric patients undergoing surgery
      for congenital heart repair.
AB  - Macrophage migration inhibitory factor (MIF), a proinflammatory mediator, has
      been shown to be elevated following heart surgery in adults and may be associated
      with several postoperative complications, including cardiac and pulmonary
      dysfunction. In this study, we aimed to measure perioperative plasma MIF,
      interleukin (IL)-8, and free T4 in 20 children age <4 years undergoing surgical
      repair of congenital heart lesions with left ventricular volume overload, and to
      determine whether the response of these mediators determined postoperative
      outcomes. Plasma samples were obtained preoperatively, immediately on arrival in
      the pediatric intensive care unit (PICU), and at 12, 24, and 48 h. Patients were
      continuously monitored in the PICU, and data were recorded daily for therapeutic
      and monitoring procedures that reflected the invasiveness, intensity, and
      complexity of care rendered (therapeutic interventional scoring system, TISS).
      Preoperative plasma MIF, IL-8, and free T4 were not different from age-matched
      healthy children. However, plasma MIF and IL-8 increased significantly 2 h after
      completion of cardiopulmonary bypass, and then normalized within 24 h. Peak
      postoperative levels of MIF (48 +/- 24 ng/mL) and IL-8 (79 +/- 57 pg/mL)
      correlated significantly with duration of cardiopulmonary bypass. The magnitude
      of the postoperative increase in plasma MIF was associated with increased number
      of days required for mechanical ventilation (r = 0.553; P = 0.012), and peak
      plasma IL-8 correlated significantly with the fraction of inhaled oxygen (FiO(2))
      required immediately after surgery (r = 0.510; P = 0.02). Higher circulating MIF
      levels correlated significantly with increased inotropic support requirements on
      the second postoperative day, whereas higher postoperative IL-8 levels were
      associated with higher TISS scores, suggesting increased need for postoperative
      medical care. These data suggest a potential negative effect of high circulating
      levels of MIF in the immediate postoperative period on respiratory and
      cardiovascular functions, and support the development of therapeutic strategies
      targeting MIF function in this clinical setting.

PMID- 18079995
TI  - Catecholamines-crafty weapons in the inflammatory arsenal of immune/inflammatory
      cells or opening pandora's box?
AB  - It is well established that catecholamines (CAs), which regulate immune and
      inflammatory responses, derive from the adrenal medulla and from presynaptic
      neurons. Recent studies reveal that T cells also can synthesize and release
      catecholamines which then can regulate T cell function. We have shown recently
      that macrophages and neutrophils, when stimulated, can generate and release
      catecholamines de novo which, then, in an autocrine/paracrine manner, regulate
      mediator release from these phagocytes via engagement of adrenergic receptors.
      Moreover, regulation of catecholamine-generating enzymes as well as degrading
      enzymes clearly alter the inflammatory response of phagocytes, such as the
      release of proinflammatory mediators. Accordingly, it appears that phagocytic
      cells and lymphocytes may represent a major, newly recognized source of
      catecholamines that regulate inflammatory responses.

PMID- 18079999
TI  - Investigating lipid interactions and the process of raft formation in cellular
      membranes using ToF-SIMS.
AB  - There is an increased interest in how lipids interact with each other, especially
      in the lateral separation of lipids into coexisting liquid phases as this is
      believed to be an attribute of raft formation in cell membranes. ToF-SIMS has
      shown itself to be an excellent tool for investigating cellular and model
      membrane systems and will be perhaps the most powerful one for investigating raft
      formation. Results from our laboratory show the capability of ToF-SIMS at
      identifying unequivocally the content of coexisting liquid lipid phases. Using
      supported lipid monolayers we find that the inclusion of
      dipalmitoylphosphatidylethanolamine (DPPE) to a homogeneous
      dipalmitoylphosphatidylcholine (DPPC)/cholesterol phase results in the formation
      of cholesterol-rich domains [A.G. Sostarecz, C.M. McQuaw, A.G. Ewing, N.
      Winograd, J. Am. Chem. Soc. 126 (2004) 13882]. Also, for DPPE/cholesterol systems
      a single homogeneous DPPE/cholesterol phase is formed at ~50 mol% cholesterol,
      whereas DPPC/cholesterol systems form a single phase at 30 mol% cholesterol [C.M.
      McQuaw, A. Sostarecz, L. Zheng, A.G. Ewing, N. Winograd, Langmuir 21 (2005) 807].
      Currently we are exploring the incorporation of sphingomyelin into phospholipid
      cholesterol mixtures in an effort to gain a better understanding of its role in
      raft formation.

PMID- 18079998
TI  - alpha-Lipoic acid modulates extracellular matrix and angiogenesis gene expression
      in non-healing wounds treated with hyperbaric oxygen therapy.
AB  - alpha-Lipoic acid (LA) has been found previously to accelerate wound repair in
      patients affected by chronic wounds who underwent hyperbaric oxygen (HBO)
      therapy. Because proteinases are important in wound repair, we hypothesized that
      LA may regulate matrix metalloproteinase (MMP) expression in cells that are
      involved in wound repair. Patients undergoing HBO therapy were double-blind
      randomized into two groups: the LA group and the placebo group. Gene expression
      profiles for MMPs and for angiogenesis mediators were evaluated in biopsies
      collected at the first HBO session, at the seventh HBO session, and after 14 days
      of HBO treatment. ELISA tests were used to validate microarray expression of
      selected genes. LA supplementation in combination with HBO therapy downregulated
      the inflammatory cytokines and the growth factors which, in turn, affect MMPs
      expression. The disruption of the positive autocrine feedback loops that maintain
      the chronic wound state promotes progression of the healing process.

PMID- 18080000
TI  - The Effects of Age Composition of 12-Step Groups on Adolescent 12-Step
      Participation and Substance Use Outcome.
AB  - Youth substance use disorder treatment programs frequently advocate integration
      into 12-Step fellowships to help prevent relapse. However, the effects of the
      predominantly adult composition of 12-step groups on adolescent involvement and
      substance use outcome remain unstudied. Greater knowledge could enhance the
      specificity of treatment recommendations for youth. To this end, adolescents (N =
      74; M age = 15.9, 62% female) were recruited during inpatient treatment and
      followed up 3 and 6 months later. Greater age similarity was found to positively
      influence attendance rates and the perceived importance of attendance, and was
      marginally related to increased step-work and less substance use. These
      preliminary findings suggest locating and directing youth to meetings where other
      youth are present may improve 12-step attendance, involvement, and substance use
      outcomes.

PMID- 18080001
TI  - Aging and Visual Attention.
AB  - Older adults are often slower and less accurate than are younger adults in
      performing visual-search tasks, suggesting an age-related decline in attentional
      functioning. Age-related decline in attention, however, is not entirely
      pervasive. Visual search that is based on the observer's expectations (i.e., top
      down attention) is relatively preserved as a function of adult age. Neuroimaging
      research suggests that age-related decline occurs in the structure and function
      of brain regions mediating the visual sensory input, whereas activation of
      regions in the frontal and parietal lobes is often greater for older adults than
      for younger adults. This increased activation may represent an age-related
      increase in the role of top-down attention during visual tasks. To obtain a more
      complete account of age-related decline and preservation of visual attention,
      current research is beginning to explore the relation of neuroimaging measures of
      brain structure and function to behavioral measures of visual attention.

PMID- 18080002
TI  - The Social and Economic Impact of Sanctions and Time Limits on Recipients of
      Temporary Assistance to Needy Families.
AB  - A central feature of the reforms enacted through the Personal Responsibility and
      Work Opportunity Reconciliation Act (welfare reform) has been the adoption of
      strategies to involuntarily remove Temporary Assistance to Needy Families (TANF)
      recipients from the welfare rolls, including increased use of sanctions and time
      limits on welfare receipt. Drawing on data from a three year panel study of women
      who had been receiving welfare in a state which adopted stringent sanctioning and
      time limit policies, we investigate predictors of recipients' TANF status after
      implementation of welfare reform, and identify differences in post-reform
      material resources, hardships and quality of life based on TANF status. Almost
      half of all welfare case closures during the first time period after reforms were
      implemented through involuntary strategies. Relatively few baseline
      characteristics predicted different outcomes once welfare time limits and
      sanctions were implemented. Those who were timed off welfare had substantially
      lower incomes in the year following their removal. One third of all respondents,
      regardless of reason for leaving TANF reported having insufficient food, housing
      problems and lack of access to needed medical care.

PMID- 18080003
TI  - In vitro microscopic imaging of enhanced thrombolysis with 120-kHz ultrasound in
      a human clot model.
AB  - Substantial enhancement of recombinant tissue plasminogen activator (rt-PA)
      thrombolysis can be achieved with ultrasound, suggesting its use as an adjunctive
      treatment in thrombolytic therapy for stroke. A microscopic visualization method
      was used to measure the lysis of human whole-blood clots treated with human fresh
      frozen plasma (HFFP), rt-PA, and 120-kHz ultrasound for 30 min at T = 37  degrees
      C. The clot-plasma interface was imaged using an inverted optical microscope and
      the thrombolytic front analyzed as a function of time. Ultrasound treatment
      significantly enhanced the mean lytic rate from 0.5 to 3.4 MUm/min (a 580%
      change) compared with rt-PA treatment alone.

PMID- 18080004
TI  - SPELLING CORRECTION IN THE PUBMED SEARCH ENGINE.
AB  - It is known that users of internet search engines often enter queries with
      misspellings in one or more search terms. Several web search engines make
      suggestions for correcting misspelled words, but the methods used are proprietary
      and unpublished to our knowledge. Here we describe the methodology we have
      developed to perform spelling correction for the PubMed search engine. Our
      approach is based on the noisy channel model for spelling correction and makes
      use of statistics harvested from user logs to estimate the probabilities of
      different types of edits that lead to misspellings. The unique problems
      encountered in correcting search engine queries are discussed and our solutions
      are outlined.

PMID- 18080005
TI  - Temperamental and Joint Attentional Predictors of Language Development.
AB  - Individual differences in child temperament have been associated with individual
      differences in language development. Similarly, relationships have been reported
      between early nonverbal social communication (joint attention) and both
      temperament and language. The present study examined whether individual
      differences in joint attention might mediate temperament-language relationships.
      Temperament, language, and joint attention were assessed in 51 21-month-olds.
      Results indicated an inverse relationship between aspects of temperamental
      difficulty, including low executive control and high negative affect, and
      language development. Temperamental aspects of negative affect were also
      inversely predictive of joint attention. However, the utility of a model in which
      joint attention mediates the relationship between temperament and language during
      the second year was not supported.

PMID- 18080006
TI  - Two-Term Asymptotic Approximation of a Cardiac Restitution Curve.
AB  - If spatial extent is neglected, ionic models of cardiac cells consist of systems
      of ordinary differential equations (ODEs) which have the property of
      excitability, i.e., a brief stimulus produces a prolonged evolution (called an
      action potential in the cardiac context) before the eventual return to
      equilibrium. Under repeated stimulation, or pacing, cardiac tissue exhibits
      electrical restitution: the steady-state action potential duration (APD) at a
      given pacing period B shortens as B is decreased. Independent of ionic models,
      restitution is often modeled phenomenologically by a one-dimensional mapping of
      the form APD(next) = f(B - APD(previous)). Under some circumstances, a
      restitution function f can be derived as an asymptotic approximation to the
      behavior of an ionic model.In this paper, extending previous work, we derive the
      next term in such an asymptotic approximation for a particular ionic model
      consisting of two ODEs. The two-term approximation exhibits excellent
      quantitative agreement with the actual restitution curve, whereas the leading
      order approximation significantly underestimates actual APD values.

PMID- 18080009
TI  - Motivational Antecedents of Preventive Proactivity in Late Life: Linking Future
      Orientation and Exercise.
AB  - Future orientation is considered as a motivational antecedent of late-life
      proactivity. In a panel study of 453 old-old adults, we linked future orientation
      to exercise, a key component of late-life proactivity. Findings based on
      hierarchical linear modeling reveal that future orientation at baseline predicts
      changes in exercise during the subsequent four years. Whereas exercise behavior
      generally declined over time, future orientation and female gender were
      associated with smaller decline. These results suggest that future-oriented
      thinking has a lasting impact on health promotion behavior. Future orientation
      thus represents a dispositional antecedent of preventive proactivity as proposed
      in our successful aging model.

PMID- 18080007
TI  - Cholinergic interneurons are differentially distributed in the human striatum.
AB  - BACKGROUND: The striatum (caudate nucleus, CN, and putamen, Put) is a group of
      subcortical nuclei involved in planning and executing voluntary movements as well
      as in cognitive processes. Its neuronal composition includes projection neurons,
      which connect the striatum with other structures, and interneurons, whose main
      roles are maintaining the striatal organization and the regulation of the
      projection neurons. The unique electrophysiological and functional properties of
      the cholinergic interneurons give them a crucial modulating function on the
      overall striatal response. METHODOLOGY/PRINCIPLE FINDINGS: This study was carried
      out using stereological methods to examine the volume and density (cells/mm(3))
      of these interneurons, as visualized by choline acetyltransferase (ChAT)
      immunoreactivity, in the following territories of the CN and Put of nine normal
      human brains: 1) precommissural head; 2) postcommissural head; 3) body; 4) gyrus
      and 5) tail of the CN; 6) precommissural and 7) postcommissural Put. The
      distribution of ChAT interneurons was analyzed with respect to the topographical,
      functional and chemical territories of the dorsal striatum. The CN was more
      densely populated by cholinergic neurons than the Put, and their density
      increased along the anteroposterior axis of the striatum with the CN body having
      the highest neuronal density. The associative territory of the dorsal striatum
      was by far the most densely populated. The striosomes of the CN precommissural
      head and the postcommissural Put contained the greatest number of ChAT-ir
      interneurons. The intrastriosomal ChAT-ir neurons were abundant on the periphery
      of the striosomes throughout the striatum. CONCLUSIONS/SIGNIFICANCE: All these
      data reveal that cholinergic interneurons are differentially distributed in the
      distinct topographical and functional territories of the human dorsal striatum,
      as well as in its chemical compartments. This heterogeneity may indicate that the
      posterior aspects of the CN require a special integration of information by
      interneurons. Interestingly, these striatal regions have been very much left out
      in functional studies.

PMID- 18080010
TI  - Gerontology at Case Western Reserve University: A History of Pioneering
      Scholarship.

PMID- 18080011
TI  - Homeopathy, fundamentalism, and the memory of water.

PMID- 18080013
TI  - Broad funding for oxaliplatin in Ontario (finally!).

PMID- 18080014
TI  - Anemia is a common but neglected complication of adjuvant chemotherapy for early
      breast cancer.
AB  - In this study, we set out to determine the frequency and severity of anemia and
      the corrective interventions used during adjuvant chemotherapy for breast
      cancer.We conducted a retrospective electronic chart review of 702 patients who
      received adjuvant breast cancer chemotherapy at four BC Cancer Agency centres in
      2002 and 2003. For these patients, we recorded the initial hemoglobin reading and
      the date of the first hemoglobin reading in the ranges 110-119 g/L, 100-109 g/L,
      90-99 g/L, and <90 g/L. We also recorded any discussion about, or delivery of,
      interventions for anemia [transfusion, epoetin (epo) or both].Median age of the
      study population was 51 years, and it varied with chemotherapy type. Among the
      patients, 12% had a hemoglobin reading <120 g/L before the start of chemotherapy.
      Overall, the proportion of patients with at least one hemoglobin reading <120 g/L
      was 78%; <110 g/L, 54%; <100 g/L, 31%; and <90 g/L, 14%. Depending on
      chemotherapy type, a hemoglobin reading <100 g/L occurred in 5% to 54% of
      patients. Intervention rates increased as hemoglobin declined. For 99 patients
      with a hemoglobin reading <90 g/L, a discussion of anemia was documented in the
      treatment chart in 49% of cases, a transfusion was delivered in 23%, epo was used
      in 11%, and transfusion and epo were both delivered in 5%.Anemia was relatively
      common and varied with chemotherapy type. Documentation of a discussion of anemia
      occurred in fewer than 20% of the patients with a hemoglobin reading of 90-99 g/L
      and in only half the patients with a hemoglobin reading <90 g/L. Intervention
      rates were low at hemoglobin readings for which randomized trials have shown that
      intervention can improve quality of life.

PMID- 18080015
TI  - Integrating regional and community lung cancer services to improve patient care.
AB  - Lung cancer is the leading cause of cancer death in Canada. The organization of
      health care services is central to the delivery of accessible, high-quality
      medical care and may be one factor that influences patient outcome. An exciting
      opportunity arose for clinicians to initiate the redesign of lung cancer services
      provided by three institutions in the Greater Toronto Area. This qualitative
      report describes the integrated lung cancer network that they developed, the
      innovation it has facilitated, and the systematic approach being taken to
      evaluate its impact. Available clinical resources were deployed to restructure
      services along patient-centred lines and to provide greater access to the
      specialist lung cancer team. A non-hierarchical clinical network was established
      that consolidates the lung cancer team. A multi-institutional and
      multidisciplinary tumour board and comprehensive thoracic oncology clinics are at
      its core. This innovative organizational paradigm considers all of the available
      services at each facility and aims to fully integrate specialists across the
      three institutions, thereby maximizing resource utilization. We believe that this
      paradigm may have wider applicability. The network is currently working to
      complete a current program of further service improvements and to objectively
      assess its impact on patient outcome.

PMID- 18080016
TI  - Role of vaccine therapy in cancer: biology and practice.
AB  - Vaccines constitute a potential new therapeutic approach for a range of human
      cancers. Unlike other therapeutics, vaccines initiate a dynamic process in the
      host immune system that can be exploited with subsequent therapies. Indeed,
      recent preclinical and clinical studies with cancer vaccines have provided
      evidence that this unique therapeutic modality should lead to consideration of
      new paradigms in both clinical trial design and endpoints and in combination
      therapies. The present article reviews and sets out a rationale for these new
      paradigms, with a focus on prostate cancer.

PMID- 18080017
TI  - The antitumour activities of statins.

PMID- 18080018
TI  - Studies on oligosaccharyl transferase in yeast.
AB  - In yeast, OT consists of nine different subunits, all of which contain one or
      more predicted transmembrane segments. In yeast, five of these proteins are
      encoded by essential genes, Swp1p, Wbp1p, Ost2p, Ost1p and Stt3p. Four others are
      not essential Ost3p, Ost4p, Ost5p, Ost6p. All yeast OT subunits have been cloned
      and sequenced (Kelleher et al., 1992; 2003; Kelleher & Gilmore, 1997; Kumar et
      al., 1994; 1995; Breuer & Bause, 1995) and the structure of one of them, Ost4p,
      has been solved by NMR (Zubkov et al., 2004). Very recently, the preliminary
      crystal structure of the lumenal domain of an archaeal Stt3p homolog has been
      reported (Mayumi et al., 2007). Homologs of all OT subunits have been identified
      in higher eukaryotic organisms (Kelleher et al., 1992; 2003; Kumar et al., 1994;
      Kelleher & Gilmore, 1997).

PMID- 18080019
TI  - Leukemic stem cells: from metabolic pathways and signaling to a new concept of
      drug resistance targeting.
AB  - Cancer stem cells are a small subset of cancer cells constituting a reservoir of
      self-sustaining cells with the exclusive ability to self-renew and maintain the
      tumor. These cells are identified by specific stem cell markers: antigens,
      molecules and signaling pathways. Transcription factors and molecules associated
      with oncogenesis, such as NF-kappaB, Bmi-1, Notch, WNT beta-catenin, Sonic
      hedgehog and their biochemical pathways, active only in a small minority of
      cancer cells might play key roles in determining the biology and the overall long
      term behavior of a tumor. The molecules and pathways specific for cancer stem
      cells, which contribute to their drug resistance, are potential targets for new
      therapeutic strategies.

PMID- 18080020
TI  - Response of Acanthamoeba castellanii mitochondria to oxidative stress.
AB  - The purpose of this study was to examine the effects of oxidative stress caused
      by hydroperoxide (H(2)O(2)) in the presence of iron ions (Fe(2+)) on mitochondria
      of the amoeba Acanthamoeba castellanii. We used isolated mitochondria of A.
      castellanii and exposed them to four levels of H(2)O(2) concentration: 0.5, 5,
      15, and 25 mM. We measured basic energetics of mitochondria: oxygen consumption
      in phosphorylation state (state 3) and resting state (state 4), respiratory
      coefficient rates (RC), ADP/O ratios, membrane potential (DeltaPsi(m)), ability
      to accumulate Ca(2+) , and cytochrome c release. Our results show that the
      increasing concentrations of H(2)O(2) stimulates respiration in states 3 and 4.
      The highest concentration of H(2)O(2) caused a 3-fold increase in respiration in
      state 3 compared to the control. Respiratory coefficients and ADP/O ratios
      decreased with increasing stress conditions. Membrane potential significantly
      collapsed with increasing hydroperoxide concentration. The ability to accumulate
      Ca(2+) also decreased with the increasing stress treatment. The lowest stress
      treatment (0.5 mM H(2)O(2)) significantly decreased oxygen consumption in state 3
      and 4, RC, and membrane potential. The ADP/O ratio decreased significantly under
      5 mM H(2)O(2) treatment, while Ca(2+) accumulation rate decreased significantly
      at 15 mM H(2)O(2). We also observed cytochrome c release under increasing stress
      conditions. However, this release was not linear. These results indicate that as
      low as 0.5 mM H(2)O(2) with Fe(2+) damage the basic energetics of mitochondria of
      the unicellular eukaryotic organism Acanthamoeba castellanii.

PMID- 18080021
TI  - Chemical synthesis of dolichyl phosphates, their analogues and derivatives and
      application of these compounds in biochemical assays.
AB  - Several methods for simple and efficient chemical synthesis of dolichyl
      phosphates and their analogues and derivatives are briefly summarized with a
      special emphasis on chemical modification of phosphoryl group and preparation of
      dolichyl phosphates labelled at the omega-end and at the gamma-isoprene unit of
      the isoprene chain by fluorescent groups, 2-aminopyridine and 1-aminonaphtalene
      residues. Additionally, data on biochemical assays with application of the
      compounds mentioned above are presented.

PMID- 18080022
TI  - Structural and functional characteristics of two novel members of pathogensis
      related multigene family of class 10 from yellow lupine+.
AB  - PR-10 proteins (pathogensis-related), ubiquitous within the plant kingdom, are
      usually encoded by multigene families. To date we have identified 10 homologous
      pr-10 genes in a yellow lupine cDNA library. Here, the structure and expression
      of two newly identified yellow lupine pr-10 genes (LlYpr10-2b and LlYpr10-2f) are
      presented. Many potential regulatory sites were found in both gene promoters
      including common ones as well as those unique for each gene. However, promoter
      deletion analysis in transgenic tobacco plants revealed similar patterns of
      reporter gene (gus) expression. Shortened fragments of both gene promoters
      studied caused high GUS activity in leaves (along vascular bundles), stamen
      stigma, anthers and pollen grains. When conjugated with longer LlYpr-10.2
      promoter fragments, GUS was additionally present in petal edges. Only a long
      fragment of the LlYpr10-2b gene promoter caused GUS expression in the stem. In
      yellow lupine the pr-10.2 genes are present in all studied organs, but their
      level of expression depends on the stage of development and is affected by
      wounding, oxidative stress and salicylic acid treatment. Silencing of the Llpr
      10.2b gene in 4-week-old yellow lupine plants did not lead to any visible
      symptoms, which suggests that the function of the silenced gene is supplemented
      by its close homologues, still present in the studied plants.

PMID- 18080023
TI  - [New advances in the treatment of chronic hepatitis B: position of entecavir].

PMID- 18080024
TI  - [Daptomycin: revitalizing a former drug due to the need of new active agents
      against grampositive multiresistant bacterias].
AB  - The development of mechanisms of resistance of many Gram-positive bacterial
      strains that cause complicated skin and soft tissue infections, as well as sepsis
      and bacteremia, has necessitated the search for new drugs that will improve
      treatment strategies. Daptomycin is a cyclic lipopeptide antibacterial that was
      launched for the treatment of complicated skin and soft tissue infections caused
      by Gram-positive organisms. The drug's mechanism of action is different from that
      of any other antibiotic. It binds to bacterial membranes and causes a rapid
      depolarization of membrane potential. This loss of membrane potential causes
      inhibition of protein, DNA and RNA synthesis, which results in bacterial cell
      death. The in vitro spectrum of activity of daptomycin encompasses most
      clinically relevant aerobic Gram-positive pathogenic bacteria. Compared to other
      antibiotics with a similar antibacterial spectrum, daptomycin does not cause
      nephrotoxicity. Taking these and other characteristics into consideration,
      daptomycin appears to be a good alternative to other drugs used in the treatment
      of complicated skin and soft tissue infections and in Gram-positive bacteremial
      infections.

PMID- 18080025
TI  - [Ertapenem].

PMID- 18080026
TI  - [Multivariate analysis used in the investigation of antimicrobials].
AB  - Multivariate analysis techniques are reviewed. The study of variables requires
      special methods with two precise objectives, the simultaneous analysis of all the
      inputs and logical support when making decisions. The most common descriptive and
      explanatory techniques are discussed. The seven common steps usually developed
      for multivariate tests implementation are shown. The creation of an advisory
      board for methodology used by research entities is proposed for the rational
      control and performance of research processes. The need for more inventors, as
      well as more financial assistance for researchers, is highlighted.

PMID- 18080027
TI  - [Biotechnologic drugs and chemotherapy for infectious diseases].
AB  - Developments in biotechnology in recent years have enabled the discovery of new
      pharmacological agents for the treatment and prophylaxis of infectious diseases.
      The agents obtained from these biotechnological procedures possess specific
      characteristics which significantly distinguish them from drugs obtained by
      chemical synthesis. These properties cover the entire development process, from
      investigation and production up to their administration to patients. The
      pharmokinetics of these preparations influence their administration routes and
      dosage regimens. The discovery of these drugs has led to major advances in the
      treatment and prophylaxis of infectious processes which until very recently had
      no effective treatment. The investigation and production of these drugs requires
      the use of highly technical resources resulting in high costs and therefore a
      more expensive drug on the market compared to other drugs. Nevertheless, well
      documented pharmoeconomic studies show that the use of this type of drug for
      certain symptoms may be highly cost effective. This article includes some of the
      possible applications of biotechnology in the infectious disease field, although
      the current situation indicates that more detailed and broader applications may
      be elaborated on in ensuing issues. The future of these drugs in chemical therapy
      for the treatment and prophylaxis of infectious diseases is exceedingly promising
      and many of these drugs are currently under laboratory investigation, more so
      than those under development from a chemical synthesis approach.

PMID- 18080028
TI  - [Phenotypes and genetic mechanisms of resistance to macrolides and lincosamides
      in viridans group streptococci].
AB  - Viridans group streptococci (VGS) are part of the oropharyngeal, intestinal and
      genital flora, but they may cause endocarditis and bacteremia in susceptible
      patients. Penicillin- and macrolide-resistant strains are increasing every year.
      The aim of this study was to investigate genetic mechanisms of resistance to
      macrolides in clinically relevant isolates. We identified 85 isolates from
      January 2004 to June 2006. Susceptibility to penicillin, cefotaxime,
      erythromycin, clindamycin and gentamycin was determined. A resistance phenotype
      was assigned according to the disk approximation test (erythromycin-clindamycin).
      The mechanism of resistance was determined by PCR for the following genes: ermB,
      ermA, ermC, ermA (TR) and mefA/E. We identified 51 isolates belonging to
      Streptococcus anginosus species, most of which were obtained from abdominal
      abscesses, and 34 isolates belonging to other species, most of which were
      obtained from blood cultures. The macrolide resistance rate was 28.2% (24/85).
      The MLS(B) phenotype was observed in 66.7% of the isolates, primarily in the S.
      anginosus group. The M phenotype was predominant in S. mitis and S. oralis.
      Isolates that expressed the constitutive MLS(B) phenotype carried the ermB gene,
      and those that expressed the inducible MLSB phenotype carried the ermA gene.
      Isolates that expressed the M phenotype carried the mefA/E gene. There was
      coresistance with penicillin in 20.8% (5/24) of the isolates. Coresistance with
      penicillin was low. These results suggest that screening for macrolide resistance
      in VGS would be desirable because of the potential transmission of resistance
      genes to other pathogenic streptococci.

PMID- 18080029
TI  - [Knowledge and attitude of primary health care doctors in the treatment of
      community-acquired infections].
AB  - The aim of this study was to evaluate the knowledge and attitude of the doctors
      who attend patients with community-acquired infections and who are responsible
      for most of the antibiotic prescriptions in primary health care. At the same
      time, the evolution experienced in the last ten years in relation to the main
      parameters analyzed was studied. The study was conducted by personal interviews,
      using a structured questionnaire, administered to 855 doctors of different
      specialties, who make up a statistically significant nationwide sample. The study
      showed that in spite of the improvements in the knowledge of the microbiology of
      infectious diseases and the choice of antimicrobial agents, there are still
      certain areas that need improvement. These are, above all, in regard to the
      bacterial resistance problem, underevaluation of the viral etiology of certain
      respiratory tract infections and the somewhat condescending attitude with "visits
      by third parties", indulgence prescriptions and therapeutic noncompliance.
      Efficacy defined not only as clinical remission but also, and essentially, as
      antibacterial coverage, are the main parameters considered when participating
      physicians choose an antibiotic.

PMID- 18080030
TI  - Fungicidal activity of a phospholipase-A2-derived synthetic peptide variant
      against Candida albicans.
AB  - pEM-2, a 13-mer synthetic peptide variant derived from myotoxin II, a
      phospholipase A(2) homologue present in Bothrops asper snake venom, has shown
      potent bactericidal activity in previous studies due to the combination of
      cationic and hydrophobic amino acids, including three tryptophan-substituted
      residues in its sequence. This study reports that pEM-2 also exerts potent
      fungicidal activity against a variety of clinically relevant Candida species,
      killing 100% of yeasts at concentrations near 10 mg/l (5 microM), as indicated by
      plate counting assays. Thus, this peptide displays a broad-spectrum antimicrobial
      activity, in the absence of hemolytic activity. The fungicidal action of pEM-2
      against Candida can be partially inhibited by increasing concentrations of
      extracellular divalent cations (Ca(+2) or Mg(+2)), in agreement with its proposed
      membrane-permeabilizing mechanism of action.

PMID- 18080032
TI  - [Epidemiological study of Staphylococcus aureus nasal carriage in senior
      centers].
AB  - The observation of an increasing number of methicillin-resistant Staphylococcus
      aureus (MRSA) isolates in some population groups prompted us to study the risk
      factors and the epidemiological profile of S. aureus nasal carriage in healthy
      adults 65 years of age and older residing in the province of Segovia. Attention
      was particularly focused on the possibility that some of the infections were
      community-acquired. We conducted a prospective and observational study of people
      who usually visited senior citizen centers in the province of Segovia (Carbonero,
      Cuellar, Cantalejo) and its capital. The analysis period took place between
      January and May 2003. Infections were classified as community-acquired, hospital
      acquired or health-care associated. Isolates of methicillin-resistant (MRSA) and
      methicillin-susceptible S. aureus (MSSA) were studied by pulsed-field gel
      electrophoresis (PFGE). There were 34 (19.5%) The prevalence of nasal carriage of
      S. aureus was 19.5% and that for MRSA was 1.1%. Female sex was significantly
      associated with the carriage state. All S. aureus isolates were mupirocin
      susceptible. 100% susceptibility and specificity was obtained through latex
      agglutination testing. The molecular study showed that the transmission for MRSA
      was monoclonal and that for MSSA was more policlonal. The results presented here
      form the basis for similar studies in other Spanish senior citizen centers and
      provide evidence that MRSA strains are beginning to circulate and are becoming
      significantly established within the community, thus highlighting the need for
      implementing control strategies to prevent dissemination.

PMID- 18080031
TI  - Activity of ertapenem and other antimicrobials against ESBL-producing
      enterobacteria isolated from urine in patients from Madrid.
AB  - The objective of this study was to evaluate the activity of ertapenem and other
      antimicrobials against extended-spectrum beta-lactamase (ESBL)-producing
      enterobacteria isolated from patients' urine samples at 4 community healthcare
      centers in the Madrid (Spain) area and to determine the prevalence of ESBL
      producing enterobacteria in community-acquired urinary tract infections. The
      antibiotic susceptibility results were compared by patient age and sex. A total
      of 293 strains were studied. The minimum inhibitory concentration (MIC) for each
      antibiotic was determined using the agar dilution method. The tested carbapenems
      were the antibiotics with the greatest activity (ertapenem MIC(90)=0.06 mg/l;
      imipenem MIC(90)=0.5 mg/l), with no intermediate or resistant strains being
      observed. High rates of resistance to ciprofloxacin (80.9%) and cotrimoxazole
      were observed (62.1%). The global prevalence of ESBL-producing enterobacteria was
      3.6% (293/8,139). Prevalence according to areas was 5.3% in Getafe, 3.45% in
      Arguelles, 3.02% in Alcala de Henares and 3.56% in Mostoles. The global
      prevalence of ESBL-producing Escherichia coli was 4.15% (279/6,721). The analysis
      of resistance according to patient sex (males versus females) showed no
      significant differences. The analysis of resistance according to patient age (<50
      years versus > or = 50 years) showed statistically significant differences (more
      resistance among subjects > or = 50 years old) for cotrimoxazole (OR=0.43, 95%CI:
      0.20-0.93, p=0.018) and ciprofloxacin (OR=0.32, 95%CI: 0.14-0.74, p=0.0027). In
      view of the good activity shown by ertapenem, and the continuous increase in the
      prevalence of ESBL strains, this antibiotic and some of the others could be a
      good choice for the treatment of community-acquired urinary tract infections
      produced by such bacteria in Spain.

PMID- 18080034
TI  - [The birth of the greatest invention of the 20th century].

PMID- 18080033
TI  - [Epidemiology of genotypic resistance of HIV-1 in Valencia. A 4-year study].
AB  - HIV resistance to antiretroviral drugs was studied in 348 samples taken from
      patients at the Molecular Biology Unit of the Microbiology Department of the
      Hospital La Fe, from January 2003 to July 2007. Once the viral load in plasma was
      determined, resistance was detected using complete gene sequencing for protease
      up to position 3464 of the HIV-1 reverse transcriptase gene. The results were
      analyzed using the Omiga 1.2 (Oxford Molecular Group) and HIV db Genotypic
      Resistance Interpretation Algorithm Version 4.3.0 (Stanford University) programs.
      The drugs least affected by the presence of mutations leading to resistance were
      the protease inhibitors darunavir, tripanavir and lopinavir (sensitivity >80%),
      the nucleoside reverse transcriptase inhibitors tenofovir and lamivudine
      (sensitivity >90%) and the non-nucleoside reverse transcriptase inhibitor TMC125
      (sensitivity >80%).

PMID- 18080035
TI  - Biological agents targeting interleukin-18.
AB  - Interleukin (IL)-18 is an important regulator of both innate and acquired immune
      responses. It is upregulated in several human autoimmune and inflammatory
      diseases, and, therefore, might represent a novel therapeutic target. This review
      highlights the biology of IL-18, its central role in inflammation and immune
      response, as well as provides evidence for the involvement of IL-18 in selected
      chronic inflammatory diseases. After that, the authors discuss various
      therapeutic strategies of IL-18 blockade in clinical and preclinical models,
      particularly the inhibition of IL-18 secretion, IL-18 binding protein, anti-IL-18
      monoclonal antibodies and soluble IL-18 receptor.

PMID- 18080036
TI  - The mTOR pathway as a potential target for the development of therapies against
      neurological disease.
AB  - The mammalian target of rapamycin (mTOR) is a protein tyrosine kinase that
      regulates cell proliferation and survival via its effects on transcription,
      translation and autophagy. The activity of mTOR is controlled by a number of
      nutrient and energy sensing pathways, inhibiting cell proliferation under
      conditions of deprivation. In addition, mTOR has been associated with the
      inhibition of apoptosis and the clearance of toxic protein aggregates. Many
      neurodegenerative diseases are characterized by neuronal death via apoptosis, and
      it is possible that modulation of mTOR activity may offer some protection against
      their effects. In particular, diseases involving oxygen and nutrient deprivation,
      such as stroke, or diseases characterized by aggregate formation, such as
      Alzheimer's and Huntington's disease, could gain substantial benefit by either
      inhibiting or enhancing mTOR activity. In addition, inhibition of mTOR in
      cancerous tissue decreases cell proliferation and increases apoptosis, and is an
      effective therapy for brain tumors. In this article, the effects of mTOR and
      their potential usefulness for the treatment of neurological disease are
      examined.

PMID- 18080037
TI  - Cellular pathways leading to neuronal dysfunction and degeneration.
AB  - There is no cure for devastating neurodegenerative disorders such as Alzheimer's,
      Parkinson's, Huntington's diseases or amyotrophic lateral sclerosis, which cause
      longterm suffering and ultimately death. Slowly progressing neurodegenerative
      diseases affect the lives of many thousands of patients and their families. These
      disorders are characterized by pathological changes in disease-specific areas of
      the brain. In each disease, these pathological processes lead to dysfunction and
      degeneration in distinct subsets of neurons. Research on neurodegenerative
      disorders has revealed a complex picture of cellular pathology involving
      abnormalities in biochemical processes, gene regulation, responses to external
      stimuli, etc. However, despite the differences in the clinical manifestations and
      selective neuronal vulnerability, on cellular and molecular levels the underlying
      pathological processes appear similar across different diseases, suggesting
      common pathways of neurodegeneration. Elucidation of the precise
      neurodegenerative mechanism(s) is essential for development of effective and safe
      therapy for these lethal human disorders.

PMID- 18080038
TI  - Tumor suppressor genes as cancer therapeutics.
AB  - Cancer formation is a multistep process that involves the sequential activation
      of oncogenes as well as the inactivation of tumor suppressor genes often in the
      same clone of cells. These genetic changes generate concomitant phenotypic
      changes in the tumor cells that allow them to continue to survive and expand.
      Over the past decade a number of genetic alterations in oncogenes and tumor
      suppressor genes have been identified and extensive research has elucidated their
      role in cellular growth, differentiation and apoptosis. Targeting tumor
      suppressor gene pathways is an attractive therapeutic strategy in cancer. This
      review summarizes the current achievements and future prospects of gene
      replacement therapy. Methods of gene delivery are described, particularly those
      that have commonly be used in clinical trials. We discuss efforts to achieve
      tissue-specific gene delivery and improved efficiency of gene delivery.

PMID- 18080039
TI  - Serotonergic drugs--a possible role in the treatment of psoriasis?
AB  - Psoriasis is a chronic inflammatory skin disease, where specific immunity and/or
      innate immunity may be of importance in the disease pathogenesis. Psoriasis may
      be worsened by stress, which suggests that a neuroimmune interaction is
      contributing to the disease. Serotonin (5-HT) is a monoamine which besides
      general effects also has an impact on cell proliferation, migration and
      apoptosis. 5-HT exerts its effects via several receptors. 5-HT has a role in
      inflammation, and 5-HT receptors as well as its transporter protein have been
      found in psoriatic skin. 5-HT 1A receptor-positive mast cells, and 5-HT 2A
      receptor and serotonin reuptake transporter (SERT)-positive T lymphocytes may be
      targets for therapy with serotonergic drugs in psoriasis.

PMID- 18080040
TI  - Molecular basis of insulin action.
AB  - Insulin is the main anabolic and anticatabolic hormone in mammals. The
      stimulatory effect of insulin on glucose uptake in muscle and adipose tissue is a
      consequence of the rapid translocation of GLUT4 glucose transporters from an
      intracellular site to the cell surface. The actions of insulin are initiated by
      hormone binding to its cell surface receptors. Insulin receptors are ligand
      stimulated protein tyrosine kinases and phosphorylate a number of proteins, known
      as insulin receptor substrate proteins. Insulin resistance has been recognized as
      a main pathogenic factor in the development of type 2 diabetes, and has been
      associated with dyslipidemia, hypertension, endothelial dysfunction, inflammation
      and coagulative state. The current challenge is the study of impaired insulin
      signaling pathways leading to beta-cell dysfunction and its progression to type 2
      diabetes, as well as control of chronic inflammation processes that may improve
      insulin action.

PMID- 18080041
TI  - Molecule of the month. Plerixafor hydrochloride.

PMID- 18080042
TI  - Waiting for treatment for chronic pain - a survey of existing benchmarks: toward
      establishing evidence-based benchmarks for medically acceptable waiting times.
AB  - As medical costs escalate, health care resources must be prioritized. In this
      context, there is an increasing need for benchmarks and best practices in wait
      time management. In December 2005, the Canadian Pain Society struck a Task Force
      to identify benchmarks for acceptable wait times for treatment of chronic pain.
      The task force mandate included a systematic review and survey to identify
      national or international wait time benchmarks for chronic pain, proposed or in
      use, along with a review of the evidence upon which they are based. An extensive
      systematic review of the literature and a survey of International Association for
      the Study of Pain Chapter Presidents and key informants has identified that there
      are no established benchmarks or guidelines for acceptable wait times for the
      treatment of chronic pain in use in the world. In countries with generic
      guidelines or wait time standards that apply to all outpatient clinics, there
      have been significant challenges faced by pain clinics in meeting the established
      targets. Important next steps are to ensure appropriate additional research and
      the establishment of international benchmarks or guidelines for acceptable wait
      times for the treatment of chronic pain. This will facilitate advocacy for
      improved access to appropriate care for people suffering from chronic pain around
      the world.

PMID- 18080043
TI  - A randomized, double-blind, placebo-controlled clinical trial using a low
      frequency magnetic field in the treatment of musculoskeletal chronic pain.
AB  - Exposure to a specific pulsed electromagnetic field (PEMF) has been shown to
      produce analgesic (antinociceptive) effects in many organisms. In a randomized,
      double-blind, sham-controlled clinical trial, patients with either chronic
      generalized pain from fibromyalgia (FM) or chronic localized musculoskeletal or
      inflammatory pain were exposed to a PEMF (400 microT) through a portable device
      fitted to their head during twice-daily 40 min treatments over seven days. The
      effect of this PEMF on pain reduction was recorded using a visual analogue scale.
      A differential effect of PEMF over sham treatment was noticed in patients with
      FM, which approached statistical significance (P=0.06) despite low numbers
      (n=17); this effect was not evident in those without FM (P=0.93; n=15). PEMF may
      be a novel, safe and effective therapeutic tool for use in at least certain
      subsets of patients with chronic, nonmalignant pain. Clearly, however, a larger
      randomized, double-blind clinical trial with just FM patients is warranted.

PMID- 18080044
TI  - Pain due to multiple sclerosis: analysis of the prevalence and economic burden in
      Canada.
AB  - BACKGROUND: Multiple sclerosis (MS) is a neurological disease affecting
      approximately 50,000 Canadians. Although studies have described overall MS costs,
      none have focused specifically on MS-related pain. OBJECTIVES: To estimate the
      prevalence of MS-related pain in Canada, the proportion of patients treated and
      responding to treatment for MS-related pain, and the associated economic burden.
      METHODS: Results were captured through physician and patient surveys. Patients
      were recruited through MS clinics and the MS Society. Patient-reported outcomes
      and resource utilization over the previous six months were collected by telephone
      interview. Costs were measured in 2004 Canadian dollars. The economic burden was
      extrapolated to the population using national demographics and prevalence.
      Spearman's rho assessed the relationship between cost and pain severity. RESULTS:
      Physicians estimated that 46% of their MS patients experienced MS-related pain,
      and that 35% received treatment for pain. Pain was reported to be relieved
      somewhat in 29%+/-10% of their patients, adequately in 26%+/-19% and poorly in
      27%+/-13%, while 17%+/-9% received no relief. Two hundred ninety-seven
      participants completed the patient survey. Seventy-one per cent (211 of 297
      patients) experienced MS-related pain. Eighty per cent of patients reported
      taking some type of medication to manage their pain, and of these, 82% reported
      some reduction in pain. The mean +/- SD direct cost per patient of MS-related
      pain was dollars 2,528+/-5,695. The mean +/- SD indirect cost per patient was
      dollars 669+/-875. Total costs were positively correlated with levels of self
      reported pain (rho=0.291, rho<0.0001). The estimated six-month burden of pain of
      MS patients in Canada was dollars 79,444,888. CONCLUSIONS: The prevalence of pain
      is high in MS patients. This condition may be underdiagnosed and undertreated,
      and results in a significant economic burden on society.

PMID- 18080045
TI  - Anxiety sensitivity, fear of pain and pain-related disability in children and
      adolescents with chronic pain.
AB  - BACKGROUND: Converging lines of evidence suggest that anxiety sensitivity and
      fear of pain may be important vulnerability factors in the development of
      avoidance behaviours and disability in adults with chronic pain. However, these
      factors have not been evaluated in children with chronic pain. OBJECTIVES: To
      examine the relationships among anxiety sensitivity, fear of pain and pain
      related disability in children and adolescents with chronic pain. METHODS: An
      interview and five questionnaires (Childhood Anxiety Sensitivity Index, Pain
      Anxiety Symptoms Scale, Functional Disability Inventory, Multidimensional Anxiety
      Scale for Children, and Reynolds Child or Adolescent Depression Scale) were
      administered to 21 children and adolescents eight to 17 years of age (mean +/- SD
      14.24+/-2.21 years) who continued to experience pain an average of three years
      after discharge from a specialized pain clinic for children. RESULTS: Anxiety
      sensitivity accounted for 38.6% of the variance in fear of pain (F[1,20]=11.30;
      P=0.003) and fear of pain accounted for 39.9% of the variance in pain-related
      disability (F[1,20]=11.95; P=0.003), but anxiety sensitivity was not
      significantly related to pain disability (R2=0.09; P>0.05). CONCLUSIONS: These
      findings indicate that children with high levels of anxiety sensitivity had a
      higher fear of pain, which, in turn, was linked to increased pain disability. The
      results of this study suggest that anxiety sensitivity and fear of pain may play
      important and distinct roles in the processes that maintain chronic pain and pain
      related disability in children.

PMID- 18080046
TI  - Pain assessment in a geriatric psychiatry program.
AB  - BACKGROUND: The assessment of pain in older persons with psychiatric illness is
      particularly challenging for health care professionals. There are few well-tested
      pain assessment tools for this population. OBJECTIVES: A study was conducted to
      explore pain assessment and management issues in geriatric psychiatry. METHODS:
      Seventy-four staff members of a geriatric psychiatry service at Regional Mental
      Health Care London, St Joseph's Health Care London, London, Ontario completed a
      survey to assess current pain assessment and management practice for geriatric
      psychiatry patients, and to identify indicators used to assess pain in this
      population. The results of the survey were later shared with members of the
      program's pain management team in a focus group discussion to explore
      opportunities on how to transfer these findings into clinical practice. RESULTS:
      The majority of survey respondents (91.8%) agreed that pain assessment and
      management could be improved for patients; only 14.9% reported that there was a
      consistent approach to pain management. Misconceptions and attitudes about pain,
      lack of easily administered pain tools, inconsistent monitoring of pain, and lack
      of documentation of pain symptoms and indicators were identified as significant
      barriers to optimal pain management for their patients. A number of behaviours
      indicative of pain were identified but emphasis was placed on recognition of
      changes from usual behaviour. CONCLUSIONS: The findings of the present study
      highlight the need for a comprehensive, practical and consistent approach to pain
      assessment and management, and provide insight into the critical components,
      including behavioural indicators, that could be incorporated into a pain protocol
      to be used with this population.

PMID- 18080047
TI  - Survey of the practice of spinal cord stimulators and intrathecal analgesic
      delivery implants for management of pain in Canada.
AB  - BACKGROUND: In 2006, the Canadian Neuromodulation Society was formed. The present
      survey characterizes the practice of spinal cord stimulator (SCS) and intrathecal
      analgesic delivery pump (IADP) implantation for pain management in different
      centres across Canada. METHOD: A structured questionnaire was designed to examine
      the funding source, infrastructure and patient screening process in different
      centres implanting SCSs and IADPs. Centres that performed more than 10 implants
      per year were surveyed. The survey was centre-based, ie, each centre received one
      questionnaire regardless of the number of staff involved in neuromodulation
      practice. RESULTS: Fourteen centres were identified and 13 responded.
      Implantation of SCS and IADP was performed in 12 and 10 centres, respectively. In
      most centres, failed back surgery syndrome was the most frequent indication for
      SCS and IADP implantation. For SCS, all centres always performed a trial; the
      majority used percutaneous electrode (83%) before the SCS implantation. Routine
      psychological screening was performed in 25% of centres before any SCS trial
      procedure. For IADP, all centres performed a trial injection or infusion before
      implantation. Five centres (50%) performed psychological screening in almost all
      patients. Continuous infusion techniques were the most popular (50%) used for the
      trial. CONCLUSION: The present survey provides a 'snapshot' of the practice of
      SCS and IADP implantation in Canada. A review of SCS and IADP trials indicated
      that Canadian practices are mostly, but not always, consistent with those
      elsewhere.

PMID- 18080048
TI  - Fifteen minutes of left prefrontal repetitive transcranial magnetic stimulation
      acutely increases thermal pain thresholds in healthy adults.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) of the motor cortex appears
      to alter pain perception in healthy adults and in patients with chronic
      neuropathic pain. There is, however, emerging brain imaging evidence that the
      left prefrontal cortex is involved in pain inhibition in humans. OBJECTIVE:
      Because the prefrontal cortex may be involved in descending pain inhibitory
      systems, the present pilot study was conducted to investigate whether stimulation
      of the left prefrontal cortex via TMS might affect pain perception in healthy
      adults. METHODS: Twenty healthy adults with no history of depression or chronic
      pain conditions volunteered to participate in a pilot laboratory study in which
      thermal pain thresholds were assessed before and after 15 min of repetitive TMS
      (rTMS) over the left prefrontal cortex (10 Hz, 100% resting motor threshold, 2 s
      on, 60 s off, 300 pulses total). Subjects were randomly assigned to receive
      either real or sham rTMS and were blind to condition. RESULTS: Subjects who
      received real rTMS demonstrated a significant increase in thermal pain thresholds
      following TMS. Subjects receiving sham TMS experienced no change in pain
      threshold. CONCLUSIONS: rTMS over the left prefrontal cortex increases thermal
      pain thresholds in healthy adults. Results from the present study support the
      idea that the left prefrontal cortex may be a promising TMS cortical target for
      the management of pain. More research is needed to establish the reliability of
      these findings, maximize the effect, determine the length of effect and elucidate
      possible mechanisms of action.

PMID- 18080049
TI  - Health care utilization and changes in health status over time for migraineurs.
AB  - BACKGROUND: Determining how migraineurs manage their condition from the viewpoint
      of health resource utilization (including both medical and personal resources)
      may provide insights that could lead to more effective care strategies.
      OBJECTIVES: To determine the relative importance of modifiable health-influencing
      activities for migraineurs, and to compare the effects of these activities
      between migraineurs and nonmigraineurs in the general population. METHODS: Linear
      regression analysis was applied to all persons older than 19 years of age with
      migraine in the Canadian Community Health Survey Cycle 1.1. The dependent
      variable was reported health status change over time. Explanatory variables were
      a series of health care utilization, health behaviour and background control
      variables. RESULTS: Results showed that health status was positively associated
      with higher levels of physical activity and negatively associated with smoking
      for both migraineurs and nonmigraineurs, even when controlling for all other
      variables. CONCLUSION: By modifying controllable resources and behaviours, the
      reported health status of migraineurs can be improved as effectively as
      nonmigraineurs.

PMID- 18080050
TI  - Canadian credentialing guidelines for endoscopic privileges: an overview.

PMID- 18080051
TI  - Prevalence of screening in patients newly diagnosed with colorectal cancer in
      Ontario.
AB  - OBJECTIVES: The primary objective was to determine the proportion of individuals
      with a new diagnosis of colorectal cancer (CRC) in Ontario in whom the cancer was
      screen detected. The secondary objectives were to determine the cancer stage at
      diagnosis and the indications for the procedure in patients who received their
      first colonoscopy. PATIENTS AND METHODS: Individuals admitted to a hospital with
      a new diagnosis of CRC were randomly selected after stratifying by hospital type
      (teaching or community). The Canadian Institute for Health Information's
      Discharge Abstract Database was used to identify individuals with a first
      diagnosis of CRC during calendar year (CY) 2000, and Ontario Health Insurance
      Plan data were used to identify people 50 to 74 years of age who had their first
      colonoscopy during CY 2000. Up to 20 individuals were selected for each group
      (CRC or colonoscopy) in each of seven randomly selected community hospitals and
      three randomly selected teaching hospitals. Data were abstracted from the
      hospital charts. RESULTS: The hospital charts of 152 patients with a new
      diagnosis of CRC were examined. Of the 133 patients in whom screening status
      could be determined, eight had screen-detected cancers (6.0%). Of the 99 patients
      (65% of the sample) in whom stage could be determined, 43 (43.4%) had advanced
      disease (tumour-node-metastasis stage III or IV) at diagnosis. The hospital
      charts of 184 patients who underwent their first colonoscopy were examined. Of
      the 175 patients in whom the indication for colonoscopy could be determined, 45
      underwent the procedure for screening purposes, 10 were for diagnostic workup of
      anemia and 120 for evaluation of symptoms. CONCLUSIONS: The low proportion (6%)
      of screen-detected CRC and the high proportion of patients (43.4%) with advanced
      disease at diagnosis reflect the lack of an organized screening program.

PMID- 18080052
TI  - Endoscopic transpapillary approach to the gallbladder for diagnosing gallbladder
      cancer.
AB  - PURPOSE: Gallbladder cancer (GBC) has a poor prognosis that is related to delayed
      diagnosis. The present study evaluated the efficacy of the transcystic ductal
      approach in diagnosing GBC. METHODS: A catheter was introduced into the
      gallbladder endoscopically via the cystic duct to obtain bile for cytology.
      Subsequently, cytology specimens were collected using a brush, and intraductal
      ultrasonography (IDUS) was performed using a miniature probe in patients
      suspected of having GBC. RESULTS: Bile cytology was performed successfully in 23
      of 25 patients (92%). The sensitivity, specificity and accuracy of cytology were
      44.4%, 100% and 78.3%, respectively. Brush cytology and IDUS were successful in
      six of eight (75%) and nine of 15 (60%) patients, respectively. Brush cytology
      was positive in two of five patients with GBC. In all four patients with invasive
      cancer, IDUS showed an irregularity or disruption of the outermost hyperechoic
      layer. CONCLUSIONS: The endoscopic transpapillary approach to the gallbladder was
      useful for the diagnosis of GBC. Brush cytology and IDUS may improve diagnostic
      efficacy and provide more useful information.

PMID- 18080053
TI  - Mode of transmission, rather than the hepatitis C virus, as a major determinant
      of poor interpersonal relationships in patients with chronic hepatitis C.
AB  - BACKGROUND: Recent studies have demonstrated that patients with the hepatitis C
      virus (HCV) have significant neurocognitive impairment. OBJECTIVE: To assess
      whether chronic HCV infection impacts on patient marital status, living
      arrangement and employment. METHODS: The charts of patients with chronic
      hepatitis C and hepatitis B were reviewed. RESULTS: The mean (+/- SD) age of the
      129 patients with the hepatitis B virus (HBV) was 46+/-15 years and that of the
      428 patients with HCV was 48+/-15 years. Sixty-seven per cent of HBV patients
      were men, compared with 68% of HCV patients. Eighty per cent of HCV patients were
      Caucasian, compared with 44% of patients with HBV. The main modes of transmission
      were intravenous drug use (37%) and transfusion of blood products (37%) for HCV,
      compared with country of origin (76%) for HBV. There were no differences in
      marital status rates between HBV- and HCV-infected patients (HBV - married (73%),
      single (21%) and divorced (6%); and HCV - married (66%), single (23%) and
      divorced (10%); P=0.20). HCV patients lived alone more often than HBV patients
      (HBV - 13%, HCV - 22%; P=0.03). There was no difference in overall employment
      rate between HCV and HBV patients (81% versus 87%; P=0.15). Though there may not
      have been overall differences between HCV and HBV marital status and employment
      status, there were differences in the HCV subgroups. These subgroup differences
      were discovered in the multivariate analysis; mode of transmission was identified
      as the only predictor of the patients' marital status and employment status.
      CONCLUSIONS: The most important determinant of interpersonal relationships was
      the mode of transmission of the viral hepatitis rather than the type of viral
      infection: past intravenous drug users had lower level relationships.

PMID- 18080054
TI  - Maintenance treatment of gastroesophageal reflux disease: an evaluation of
      continuous and on-demand therapy with rabeprazole 20 mg.
AB  - OBJECTIVE: To evaluate continuous therapy (COT) and on-demand therapy (ODT) with
      rabeprazole 20 mg for maintenance in uninvestigated gastroesophageal reflux
      disease (GERD). METHODS: This randomized, open-label study enrolled 331 GERD
      (heartburn-predominant) patients with a pre-existing proton pump inhibitor
      history of one month or longer, to an acute four-week trial with 20 mg
      rabeprazole daily for heartburn management. Patients who achieved satisfactory
      heartburn control during the acute phase (three days or less of heartburn, with
      no more than one episode rated as moderate, and heartburn rated satisfactorily or
      completely controlled with minimal rescue antacid use in the seven days preceding
      randomization) were randomly assigned to six months of rabeprazole 20 mg given as
      either daily COT or daily ODT, which was initiated upon symptom recurrence and
      stopped upon symptom resolution. Rescue antacid usage was permitted and tracked.
      Primary efficacy was measured as the proportion of heartburn-free days over six
      months. RESULTS: For the 268 patients, the mean percentage of heartburn-free days
      for the COT group and for the ODT group were 90.3%+/-14.8% and 64.8%+/-22.3%,
      respectively (P<0.0001). COT was associated with an increased number of
      medication intake days (154+/-40.2) versus ODT (68+/-46.1), with less heartburn
      episodes observed with COT versus ODT, respectively (n=7, n=26, P<0.0001). Ninety
      two per cent of COT patients and 79% of ODT patients were either 'satisfied' or
      'very satisfied' with treatment. The mean usage of antacids was low and similar
      in both groups. COT and ODT regimens were safe and well-tolerated, with a similar
      incidence of adverse events. CONCLUSION: Results based on symptom assessments
      favour COT with rabeprazole 20 mg for maintenance therapy in patients with
      uninvestigated GERD; however, both therapy types are safe and acceptable
      treatment options for selected patients.

PMID- 18080055
TI  - Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared to 2.4 g/day
      (400 mg tablets) for the treatment of mildly to moderately active ulcerative
      colitis: The ASCEND I trial.
AB  - BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown
      to be effective in treating mildly to moderately active ulcerative colitis (UC),
      but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4
      g/day in patients with mildly to moderately active UC and in the subgroup with
      moderate disease. PATIENTS AND METHODS: A six-week, multicentre, randomized,
      double-blind, controlled trial assessing the safety and clinical efficacy of a
      new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to
      moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet
      [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was
      overall improvement (ie, treatment success), defined as complete remission or
      response to therapy from baseline to week 6. Primary safety end points were
      adverse events and laboratory evaluations. Data were also analyzed separately for
      the prespecified subgroup of patients with moderate UC at baseline. RESULTS:
      Treatment success was not statistically different between the treatment groups at
      week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine
      2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the
      efficacy end point (P=0.441). Among the moderate disease subgroup, however, the
      higher initial dose was more effective; 57% of patients (53 of 93) given delayed
      release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day
      achieved treatment success (P=0.0384). Both regimens were well tolerated.
      CONCLUSIONS: Delayed-release oral mesalamine is an effective and well-tolerated
      initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day
      dose may enhance treatment success rates in patients with moderate disease
      compared with mesalamine 2.4 g/day.

PMID- 18080056
TI  - Refractory Crohn's disease of the vulva treated with infliximab: a case report.
AB  - Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disorder
      of the gastrointestinal tract. The common presentation includes abdominal pain,
      abdominal cramping and diarrhea. Many patients may exhibit systemic symptoms of
      fever and weight loss. Approximately 20% to 40% of patients will experience
      extraintestinal manifestations that involve the eyes, skin and joints. Women may
      experience a variety of gynecological manifestations, including vulvovaginal
      involvement, which is often not recognized and also difficult to treat. A case of
      refractory vulvovaginal CD is presented and the literature of gynecological
      manifestations of CD and its treatment are reviewed.

PMID- 18080057
TI  - Elastography in hepatology.
AB  - A common characteristic of all chronic liver diseases is the occurrence and
      progression of fibrosis toward cirrhosis. Consequently, liver fibrosis assessment
      plays an important role in hepatology. Besides its importance for prognosis,
      determining the level of fibrosis reveals the natural history of the disease and
      the risk factors associated with its progression, to guide the antifibrotic
      action of different treatments. Currently, in clinical practice, there are three
      available methods for the evaluation of liver fibrosis: liver biopsy, which is
      still considered to be the 'gold standard'; serological markers of fibrosis and
      their mathematical combination - suggested in recent years to be an alternative
      to liver biopsy - and, more recently, transient elastography (TE). TE is a new,
      simple and noninvasive method used to measure liver stiffness. This technique is
      based on the progressing speed of an elastic shear wave within the liver.
      Currently, there are only a few studies that have evaluated TE effectiveness in
      chronic liver diseases, mostly in patients infected with the hepatitis C virus.
      Further studies are needed in patients with chronic liver disease, to assess the
      effectiveness of the fibrosis treatment.

PMID- 18080058
TI  - Who provides gastrointestinal endoscopy in Canada?
AB  - PURPOSE: To determine who provides gastrointestinal endoscopy in Canada and to
      understand provincial and regional differences in endoscopy providers. METHODS:
      Aggregate physician sociodemographic and activity data for 2002 were obtained
      from the Canadian Institute of Health Information's National Physician Database.
      Physicians were classified as gastroenterologists, general surgeons and others.
      RESULTS: In 2002, 1444 physicians, including 735 surgeons, 551
      gastroenterologists and 158 others, performed at least 100 colonoscopies or 100
      gastroscopies. Gastroenterologists performed 53% of all colonoscopies and 59% of
      all gastroscopies. Gastroenterologists were the primary providers of
      colonoscopies in large urban areas, whereas surgeons were the primary providers
      in smaller urban and rural areas. An average of 317 colonoscopies were performed
      by surgeons, 516 by gastroenterologists and 203 by other physicians. The
      proportion of surgeon colonoscopists in each province ranged from 47% to 71%.
      CONCLUSIONS: Surgeons and gastroenterologists are the major providers of
      gastrointestinal endoscopy in Canada, but the distribution of these providers
      among provinces and urban and rural areas varies. Although surgeon endoscopists
      are more numerous, on average, they perform fewer procedures annually than
      internists.

PMID- 18080059
TI  - Combined pharmacotherapies and behavioral interventions for alcohol dependence
      (The COMBINE Study): examination of posttreatment drinking outcomes.
AB  - OBJECTIVE: The aim of this study was to examine the efficacy of pharmacological
      and behavioral interventions across 1 year posttreatment in the COMBINE
      (Combining Medications and Behavioral Interventions) Study. METHOD: Alcohol
      dependent individuals (N = 1,383; 428 women) recruited at 11 outpatient academic
      alcoholism-treatment clinics across the United States participated in a
      randomized, double-blind, placebo-controlled trial. They received 16 weeks of
      naltrexone (Revia) or acamprosate (Campral) or both medications and/or placebos
      in combination with medical management (MM), with or without combined behavioral
      intervention (CBI); one group received CBI without pills or MM. Drinking behavior
      and clinical status were assessed at the end of treatment (Week 16) and at Weeks
      26, 52, and 68. RESULTS: Prior treatment with active naltrexone, without active
      acamprosate or CBI or with active acamprosate plus CBI, and CBI with double
      placebo resulted in a significantly higher percentage of days abstinent than
      double placebos with no CBI (p < .05). Having received CBI was associated with
      positive clinical response posttreatment, compared with not having received CBI.
      Prior treatment with naltrexone increased the time to the first heavy-drinking
      day posttreatment (p = .03). No differences were found between patients who had
      received CBI without MM or pills and those having received MM and double placebo
      with or without CBI. No significant main effects for acamprosate were found on
      any of the outcome measures. CONCLUSIONS: Previous treatment with MM and either
      CBI or naltrexone, or both, but not acamprosate, was associated with sustained
      efficacy beyond discontinuation. Reasons for the maintained treatment gains with
      naltrexone and/or CBI and potential methods to extend them are discussed.

PMID- 18080060
TI  - A brief intervention for at-risk drinking in an employee assistance program.
AB  - OBJECTIVE: The current pilot study examined the preliminary efficacy of a brief
      intervention (BI) for at-risk drinking in an employee assistance program. METHOD:
      Clients (N = 107) entering the employee assistance program (EAP) for mental
      health services were screened and met criteria for at-risk drinking. EAP
      therapists were randomly assigned to deliver either the BI plus EAP services as
      usual (SAU) or SAU only. Participants in the final analyses consisted of 44 BI +
      SAU (30 women, 14 men) and 30 SAU (21 women, 9 men) EAP clients who completed a 3
      month follow-up. RESULTS: Results suggested that participants in the BI + SAU
      group had significant reductions in peak blood alcohol concentration, peak
      quantity, and alcohol-related consequences compared with the SAU group. Men in
      the BI + SAU group had greater reductions in alcohol-related problems compared
      with men in the SAU group. Groups did not differ by number of total EAP sessions
      attended or rates of presenting problem resolution. CONCLUSIONS: Results provide
      preliminary evidence to support the integration of alcohol screening and BI as a
      low-cost method of intervening with clients with at-risk drinking in the context
      of co-occurring presenting problems.

PMID- 18080061
TI  - Network support for drinking: an application of multiple groups growth mixture
      modeling to examine client-treatment matching.
AB  - OBJECTIVE: The current study re-examined the Project MATCH (Matching Alcoholism
      Treatments to Client Heterogeneity) hypothesis that individuals with high network
      support for drinking would have the best treatment outcomes if they were assigned
      to twelve-step facilitation (TSF). METHOD: Drinking consequences, as measured by
      the Drinking Inventory of Consequences, was the primary outcome measure. Growth
      mixture models with multiple groups were used to estimate the drinking
      consequence trajectories of 952 outpatients during the 12 months following
      treatment for each of the three Project MATCH treatment conditions. Growth
      factors within latent trajectory classes were regressed on network support for
      drinking to assess whether treatment condition moderated the relationship between
      network support for drinking and drinking consequences over time. RESULTS: Three
      latent classes were identified, representing low (n = 154, 16.2%), medium (n =
      400, 42%), and high (n = 398, 41.8%) levels of drinking consequences. Classes did
      not differ across treatment groups. Greater network support for drinking
      predicted more drinking consequences over time but only for clients assigned to
      cognitive-behavioral therapy and motivational enhancement therapy, not TSF.
      CONCLUSIONS: This study provides further support for one of the original Project
      MATCH matching hypotheses: Clients with social networks supportive of drinking
      had better outcomes immediately after treatment if they were assigned to TSF.
      Because the original Project MATCH studies found this matching effect only at the
      3-year follow-up, these results add validity to the network support for drinking
      matching effect. The study also provides additional evidence that accounting for
      heterogeneity in alcohol treatment outcomes is important for accurately
      estimating treatment effectiveness.

PMID- 18080062
TI  - Is intimate partner violence associated with the use of alcohol treatment
      services? Results from the National Survey on Drug Use and Health.
AB  - OBJECTIVE: The purpose of this study was to examine (1) the prevalence of alcohol
      treatment use by intimate partner violence (IPV) type (any IPV, victimization,
      and perpetration) among problem drinkers and (2) the relationship between alcohol
      treatment use and IPV, by IPV type, in the general population. METHOD: The sample
      was drawn from the 2002 National Survey on Drug Use and Health. Black, Hispanic,
      and non-Hispanic white cohabiting respondents 18-49 years of age and who reported
      one or more alcohol problems in the past year are included in the analysis.
      Logistic regression was used to examine the relationship between alcohol
      treatment use and IPV. RESULTS: The prevalence of alcohol treatment use was
      significantly greater among individuals exposed to IPV, regardless of IPV type
      (7.4%, 7.8%, and 6.9% among those with any IPV, victimization, and perpetration,
      respectively) compared with those without reported IPV (2.8%, 2.8%, and 3.0%,
      respectively). Any IPV (adjusted odds ratio [AOR] = 1.97, 95% confidence interval
      [CI]: 1.06-3.65) and IPV victimization (AOR = 1.93, CI: 1.00-3.73), but not
      perpetration, were associated with alcohol treatment use. Male gender, alcohol
      abuse/dependence, illicit drug abuse/dependence, and serious mental illness were
      positively and significantly associated with alcohol treatment in all three
      models. CONCLUSIONS: IPV, especially victimization, may have a substantial impact
      on alcohol treatment services. Findings highlight the potential to identify IPV
      in alcohol treatment settings and provide referral and intervention services.

PMID- 18080063
TI  - Alcohol-related sexual assault victimization among adolescents: prevalence,
      characteristics, and correlates.
AB  - OBJECTIVE: The purpose of this study was to document the prevalence and describe
      the characteristics of alcohol-related sexual assault among middle and high
      school students. METHOD: A Web-based, self-administered survey was used to
      collect data on 7th- through 12th-grade students (n = 1,037) in a large
      metropolitan area in the Midwest. A modified version of the Sexual Experiences
      Survey was used to ask students about their sexual victimization experiences so
      as to examine the involvement of alcohol within specific assault events. The
      sample was equally distributed by biological gender and ethnicity (white vs
      black) and was, on average (SD), 14 (2) years of age. RESULTS: Findings from the
      study indicate that alcohol was involved in approximately 12%-20% of the assault
      cases, depending on age and gender of the respondent. For females, the presence
      of alcohol during assault differed significantly based on the location at which
      the assault occurred, ranging from 6% (at the survivor's home) to 29% (at parties
      or someone else's home). Furthermore, alcohol-related assault among females was
      more likely to involve physical force than non-alcohol-related assault.
      CONCLUSIONS: Results are discussed in light of the risk factors of alcohol
      related assault among adolescents as well as the nature of social contexts that
      fosters alcohol-related sexual assault among both adolescents and college
      students.

PMID- 18080064
TI  - Patterns of association between alcohol consumption and internalizing and
      externalizing problems in young adults.
AB  - OBJECTIVE: This study examined levels of internalizing and externalizing problems
      over the full spectrum of alcohol consumption in young adults and identified
      whether social factors account for the associations of alcohol consumption with
      internalizing and externalizing problems. METHOD: This study was a cross
      sectional random sample study among 2,258 young adult men and women from the
      general population of southwest Netherlands. Five groups were distinguished: (1)
      nondrinkers; (2) occasional drinkers (monthly or less); and regular drinkers (two
      or more times monthly) who were further classified into (3) low-level drinkers
      (one to two drinks per occasion), (4) higher-level drinkers (three to four drinks
      per occasion), or (5) excessive drinkers (five or more drinks per occasion).
      Internalizing problems and externalizing problems, social support, and negative
      social exchange were measured with standardized questionnaires. RESULTS: U-shaped
      associations were found between alcohol consumption and various internalizing
      problems. Low social support accounted for higher rates of internalizing problems
      in nondrinkers and negative social exchange accounted for higher rates of
      internalizing problems in excessive drinkers. Also, excessive drinking was
      associated with various externalizing problems. A J-shaped association was found
      between alcohol consumption and aggressive behavior, with higher rates for
      occasional and excessive drinkers compared with low-level drinkers. Negative
      social exchange partly accounted for associations between alcohol consumption and
      externalizing problems. CONCLUSIONS: Nondrinkers and excessive drinkers differ
      from low-level drinkers in risk factors for poor mental health, and these factors
      may contribute to their elevated rates of mental health problems. Interventions
      that address the experience of negative social exchange may produce both mental
      health benefits and a reduction of excessive drinking.

PMID- 18080065
TI  - The association between depressive symptoms, substance use, and HIV risk among
      youth with an arrest history.
AB  - OBJECTIVE: Juvenile justice youth are at increased risk for contracting human
      immunodeficiency virus (HIV)/sexually transmitted infections because of higher
      rates of substance use and sexual risk-taking behaviors. However, little is known
      about the relationship between depressive symptoms, substance use, and HIV risk
      among youth who traditionally present with behavioral symptoms. METHOD:
      Adolescents and young adults (N = 835) who participated in a larger multisite HIV
      prevention program in three states provided baseline data on depressive symptoms,
      substance use, sexual risk, risk attitudes, and mental health history.
      Participants were grouped as arrestees and nonarrestees based on self-reported
      arrest history. This study examined differences between juvenile arrestees with
      depressive symptoms (n = 27) and those without depressive symptoms (n = 181) on
      various substance-use, sexual-risk, and mental health outcomes. RESULTS:
      Arrestees who endorsed a clinically significant level of depressive symptoms
      reported significantly greater drug and alcohol use, greater substance use during
      sex, a lower proportion of condom use, and more psychiatric hospitalizations than
      arrestees without depressive symptoms. CONCLUSIONS: Greater depressive
      symptomatology among juvenile arrestees is associated with increased risk for
      substance use and HIV; however, these findings need to be replicated with a
      larger, more representative sample of juveniles with depressive symptoms.
      Understanding more about the association of depressive symptoms with drug
      behaviors and sexual risk among juvenile offenders, even at time of first arrest,
      is essential for creating successful substance use and HIV prevention
      interventions within the juvenile justice system.

PMID- 18080066
TI  - A dangerous transition: women's drinking and related victimization from high
      school to the first year at college.
AB  - OBJECTIVE: The current study assessed women's risk for victimization during the
      first year at college, based on changes in drinking during the transition from
      high school to college. We were specifically interested in differential risk for
      victimization based on women's change in drinking status over the transition to
      college. We compared continued abstainers with women who began drinking ("new"
      drinkers) and women who continued drinking but either decreased, increased, or
      did not change their level of weekly drinking. METHOD: Data were collected using
      a Web-based survey each fall for the first 2 years at college with one cohort (N
      = 886) of incoming freshmen women at a large state university in New York. Women
      reported on their alcohol and other drug use, psychological symptoms, number of
      sexual partners, and experiences with physical and sexual victimization for the
      year before entering college (Year 1 survey) and for the first year at college
      (Year 2 survey). RESULTS: Abstainers were significantly less likely to experience
      physical or sexual victimization during the first year at college, compared with
      drinkers. Logistic regression indicated that there were differences in the
      predictors of physical and sexual victimization during the first year at college.
      These differences included history of victimization, psychological symptoms, and
      number of sexual partners, as well as the type of change in drinking over the
      transition. CONCLUSIONS: In comparison with abstainers, having a history of
      physical victimization, greater psychological symptoms, and being a "new" drinker
      increased the odds of physical victimization, whereas having a greater number of
      current psychological symptoms, sexual partners, and increasing weekly drinking
      increased the odds of sexual victimization during the first year at college.
      These findings have implications for prevention efforts targeting young women
      entering college.

PMID- 18080068
TI  - Male at-risk drinkers with heavy episodic drinking: a subclinical diagnosis?
AB  - OBJECTIVE: The aim of this study was to examine to what extent general hospital
      inpatients with risky drinking patterns differ regarding alcohol-associated
      characteristics. In particular, we tested whether persons with at-risk and heavy
      episodic drinking (ARHE) differ from those persons with at-risk drinking only
      (AR) and heavy episodic drinking only (HE). METHOD: The participants were
      recruited using a two-stage sampling process: (1) screening and (2) diagnostic.
      All in-patients from four general hospitals, ages 18-64 years (N = 14,332), were
      systematically screened for alcohol use. For this study, men with AR, HE, or ARHE
      (n = 425) were used, and men with current alcohol dependence or alcohol abuse
      were excluded. The severity of the alcohol problem was assessed by the number of
      lifetime Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
      diagnostic criteria met. Among the participants' diseases, those that were 100%
      attributable to alcohol (assigned an alcohol-attributable fraction of 1 [AAF =
      1]) were analyzed. RESULTS: Of the sample, 35.3% of the persons were identified
      with AR, 22.6% with HE, and 42.1% with ARHE. Multinomial logistic regression
      revealed that, when controlling for age, ARHE was associated with increased odds
      of having a more severe alcohol problem (odds ratio [OR] = 2.06, confidence
      interval [CI]: 1.23-3.45), using formal help (OR = 2.21, CI: 1.02-4.79), and
      having diseases with AAF = 1 (OR = 3.43, CI: 1.58-7.43), compared with AR.
      CONCLUSIONS: Among at-risk drinkers, persons with ARHE are a special subgroup
      because there appears to be an indication of a subclinical diagnosis. To provide
      adequate intervention, future research and clinical practice should distinguish
      between different risky drinking patterns.

PMID- 18080067
TI  - A comparison of three vulnerability models for the onset of substance use in a
      high-risk sample.
AB  - OBJECTIVE: The purpose of this prospective study was to compare the following
      three vulnerability models for early-onset substance use in a high-risk sample:
      the deviance proneness model, the negative affect regulation model, and a
      comprehensive model including both delinquency and negative affect. METHOD: The
      sample included 249 15- to 19-year-old adolescents (57% children of alcoholics)
      and their fathers, all of whom were seen at follow-up 5 years later. At both
      times of measurement, participants completed a clinical psychiatric interview and
      a battery of self-report questionnaires assessing temperament, negative affect,
      delinquency, and substance use. RESULTS: Although all of the models fit the data
      well, the deviance proneness model was parsimonious and provided the best fit.
      Delinquency played a significant mediating role, whereas negative affect did not.
      Moreover, negative affect and delinquency were not significantly related to one
      another. CONCLUSIONS: Results from this study suggest that the deviance proneness
      model may be a more useful theoretical framework than the negative affect
      regulation model or a comprehensive model when examining the onset of substance
      use, particularly in a high-risk sample.

PMID- 18080069
TI  - Party behaviors and characteristics and serial drunkenness among college
      students.
AB  - OBJECTIVE: This study examined the relationships between party behaviors and
      social contextual factors for the largest party attended by college students and
      serial drunkenness by students over the 3 traditional weekend party days
      (Thursday-Saturday). METHOD: On two separate 3-day party time periods in the
      spring of 2006, a random sample of 3,600 students from two large public
      universities completed a Web-based survey. The survey was administered on a
      Sunday evening and assessed alcohol consumption, party behaviors and
      observations, and other social contextual factors occurring during the 3 previous
      days. Serial drunkenness was measured as having gotten drunk on 0-3 days for the
      specified 3-day period for students who had attended one or more parties.
      RESULTS: Multivariate analysis indicated that serial drunkenness was associated
      with being white, being single without a partner, having ridden with a drinking
      driver over the weekend, drunken behaviors by other students at the largest party
      attended, the number of drinks the student consumed before attending the party,
      the number of drinks consumed at the largest party, and the number of friends
      that attended the party with the student. A lower frequency of serial drunkenness
      was associated with the perception that alcohol was difficult to obtain.
      CONCLUSIONS: The availability of alcohol before and at the largest party attended
      over the weekend, attending the party with a larger number of friends, and
      drunken behaviors by other students at the party, plus riding with a drinking
      driver after the party, were associated with serial drunkenness over the 3-day
      period by the students at these two universities.

PMID- 18080070
TI  - Positive functioning and alcohol-use disorders from adolescence to young
      adulthood.
AB  - OBJECTIVE: This research examined the longitudinal relationship between positive
      functioning and alcohol-use disorders from late adolescence into young adulthood.
      METHOD: This study used prospective, longitudinal data from the Seattle Social
      Development Project on a contemporary sample of 808 young adult men and women
      interviewed multiple times since childhood. The analysis employed a longitudinal
      path analysis to examine the relationship between positive functioning and
      alcohol-use disorders across four time points between ages 15-18 and age 27.
      RESULTS: Positive functioning and alcohol-use disorders showed moderately strong
      continuity from adolescence through young adulthood. Positive functioning in
      adolescence predicts reduced likelihood of a diagnosis of alcohol abuse and
      dependence (as defined in Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition) at age 21, and positive functioning at age 21 predicts reduced
      likelihood of alcohol abuse and dependence at age 24 in this sample. These
      findings remain even after controlling for continuity in positive functioning and
      alcohol-use disorders, associations between positive functioning and alcohol use
      in adolescence, and sociodemographic differences attributable to gender,
      race/ethnicity, and poverty. CONCLUSIONS: Positive functioning in adolescence and
      early adulthood can decrease the probability of developing alcohol-use disorders
      in young adulthood. The data from this study suggest that promoting positive
      development in childhood, adolescence, and early adulthood should be a focus of
      programs seeking to prevent alcohol abuse and dependence. Providing continued
      support for the development of positive functioning through the transition from
      adolescence to adulthood could decrease the chance of the development of alcohol
      use disorders in adulthood.

PMID- 18080071
TI  - The contextual role of alcohol outlet density in college drinking.
AB  - OBJECTIVE: The objective of the study is to examine the relationship between the
      physical availability of off-campus alcohol and drinking outcomes among college
      students. METHOD: A multilevel analysis of students (N = 17,051) nested within
      college campuses (N = 32) was conducted. Four problem-drinking-related outcomes
      (i.e., average number of drinks when partying, frequency of drunkenness in past 2
      weeks, 30-day frequency of drinking, and greatest number of drinks in one
      sitting) along with individual level covariates of drinking were introduced at
      the student level. The physical availability of alcohol was assessed as the
      number of on-premise and off-premise alcohol outlets within 3 miles of campus per
      1,000 students enrolled. RESULTS: Higher densities of on-premise alcohol outlets
      were strongly related to drinking outcomes even after controlling for individual
      predictors of college drinking. The association indicated that the campus means
      for the average number of drinks when partying and the number of drinking
      occasions in the past 30 days were, respectively, 1.13 drinks and 1.32 occasions
      greater when the outlet density was 2 SDs higher. CONCLUSIONS: Off-campus, on
      premise outlet density is strongly associated with college-drinking outcomes.
      Given the limited number of modifiable factors that affect college drinking, on
      premise outlet density represents a potential modifiable means of addressing the
      problem.

PMID- 18080072
TI  - Differential effects of acculturation on drinking behavior in Chinese- and Korean
      American college students.
AB  - OBJECTIVE: Recent evidence suggests increasing rates of alcohol use and related
      disorders among Asian-American young adults. Relatively little research has
      focused on this group, and few studies have examined heterogeneity in drinking
      prevalence and correlates across Asian subgroups. This study examined interactive
      effects of ethnicity, acculturation, and gender on drinking behavior among Asian
      American undergraduates. METHOD: Participants were 112 Chinese Americans and 108
      Korean Americans (mean age = 19.2 years, 61% female) who completed measures of
      alcohol use, acculturation, and demographic factors. Multivariate analyses
      examined drinking behavior (defined as quantity, frequency, and duration) as a
      function of ethnicity, gender, and acculturation. RESULTS: Overall, Korean
      ethnicity predicted increased drinking, and acculturation predicted decreased
      drinking. However, acculturation interacted with ethnicity such that its
      influence was protective for Korean Americans and negligible for Chinese
      Americans. CONCLUSIONS: Previous research implicates acculturation as a risk
      factor for drinking among Asian Americans, but the current findings suggest that
      protective effects may also exist. Results also indicate that Korean ethnicity is
      a risk factor particularly in the context of low acculturation. These findings
      illustrate the need to consider ethnic subgroup differences in drinking rates and
      in risk and protective factors for alcohol use among Asian Americans.

PMID- 18080073
TI  - Drinking and drinking-related problems among heterosexual and sexual minority
      women.
AB  - OBJECTIVE: Studies of alcohol use among lesbians have typically used convenience
      samples with uncertain generalizability or general population samples with small
      numbers of lesbians. Here we compare rates of high-risk and problem drinking in a
      large sample of Chicago-area lesbians and a national sample of age- and education
      matched urban heterosexual women. METHOD: Data came from comparable face-to-face
      interviews with 405 self-identified Chicago-area lesbians and with 548 urban
      women from a U.S. national sample. Rates of hazardous drinking (heavy episodic
      drinking, intoxication, drinking-related problems, alcohol-dependence symptoms)
      were compared for exclusively heterosexual, mostly heterosexual, bisexual, mostly
      lesbian, and exclusively lesbian subgroups. RESULTS: Exclusively heterosexual
      women had lower rates than did all other women on all measures of hazardous
      drinking. Exclusively heterosexual women also reported less childhood sexual
      abuse, early alcohol use, and depression. Bisexual women reported more hazardous
      drinking indicators and depression than did exclusively or mostly lesbian women.
      CONCLUSIONS: These results indicate that sexual minority women are likely to have
      elevated risks of hazardous drinking. The differences between lesbian and
      bisexual women suggest that more attention is needed to subgroup differences
      among sexual minority women. Health care providers need to know the sexual
      identity of their patients and how their sexual identity may affect their risks
      for hazardous drinking. Higher rates of childhood sexual abuse, early drinking,
      and depression among sexual minority women suggest that these experiences may be
      important in assessing and treating problems related to their drinking, and in
      developing prevention and early intervention strategies.

PMID- 18080074
TI  - Gender differences in the relationship of community services and informal support
      to seven-year drinking trajectories of alcohol-dependent and problem drinkers.
AB  - OBJECTIVE: The purpose of this study was to examine how community service
      contacts and informal support are related to the course of drinking for dependent
      and problem-drinking persons in a population-based sample of women versus men
      over 7 years. METHOD: Alcohol-dependent (n = 600) and problem-drinking (n = 992)
      men and women were identified through probability surveys in the general
      population and treatment programs throughout a California county. Participants
      were interviewed at baseline and again 1, 3, 5, and 7 years later. Models
      predicting the differential impact of community services and informal influences
      on men and women's alcohol consumption over time were estimated using a
      multilevel mixed model, while controlling for demographic characteristics and
      problem severity. RESULTS: Dependent and problem-drinking men consumed more than
      women, yet a trend of reduced drinking over time was found for both men and
      women. Alcoholics Anonymous attendance was related to decreased consumption for
      men and women regardless of severity; contact with the mental health system was
      similarly related to decreased consumption for both genders. For problem-drinking
      women, welfare contacts were related to decreased consumption. A family
      intervention was the only informal influence that had differential effects on
      dependent and problem-drinking men and women's alcohol consumption. CONCLUSIONS:
      Findings point to the continued benefits of facilitating social support and
      mental health visits for both dependent and problem-drinking men and women.
      Developing means to identify and intervene in the range of community service
      settings, particularly in the mental health and legal system, continues to be
      important. Innovative interventions for families to encourage engagement in
      chemical dependency treatment are also warranted.

PMID- 18080075
TI  - Aging and drinking problems among mature adults: the moderating effects of
      positive alcohol expectancies and workforce disengagement.
AB  - OBJECTIVE: This article examines the relationship between aging and drinking
      problems among mature workers and the moderating effects of positive alcohol
      expectancies (PAEs) and workforce disengagement. METHOD: This longitudinal study
      collected data on mature adults (i.e., retirement eligible) in three employment
      sectors (i.e., construction, manufacturing, and transportation) over five
      periods: T1 was 6 months before their retirement eligibility date and T5 was 4
      years afterward. AtT1, 1,122 subjects participated in the survey; at T5, 917
      participated in the survey. Problem drinking was assessed in all five waves by
      the Drinking Problems Index. PAEs were measured at T4 and T5 by the Alcohol
      Outcomes Expectancies Scale. Workforce disengagement was assessed by subjects'
      employment status at T5 (i.e., still working despite eligibility versus fully
      retired/not working). Control variables were employment sector, age at T1, and
      gender. RESULTS: PAEs moderated the relationship between aging and drinking
      problems: High PAEs were associated with an increase in drinking problems,
      whereas low PAEs were associated with a decrease in drinking problems. With
      regard to disengagement, continuing to work amplified the moderating effects of
      PAEs on the relationship between aging and drinking problems, whereas the
      moderating effects of PAEs were attenuated for the fully retired. CONCLUSIONS:
      This study provides further evidence of the significance of PAEs and drinking
      problems among mature adults, particularly as they are conditioned by
      disengagement from work. Implications for employee/member assistance program are
      discussed.

PMID- 18080076
TI  - Identifying mediators of the relationship between religiousness/spirituality and
      alcohol use.
AB  - OBJECTIVE: Religiousness is known to be inversely related to alcohol use and
      problems, but few studies have attempted to identify mediators of this
      relationship. We examined beliefs about alcohol, social influences, well-being,
      and motives for drinking as potential mediators of the relationship between
      religiousness/spirituality and alcohol use and problems. METHOD: Participants
      were 315 female and 197 male college students who responded to a survey sent to a
      stratified (by gender and year in school) random sample. We used path analysis to
      test models specifying hypothesized mediators of the relationship between several
      religious/spiritual constructs (identified via factor analysis in previous
      studies) and alcohol use and problems. Models were tested in the full sample and
      a subsample consisting of alcohol users only. RESULTS: The effect of
      religious/spiritual involvement on alcohol use was mediated by negative beliefs
      about alcohol, social influences, and spiritual well-being. The effect of
      religious struggle on alcohol problems was mediated by spiritual well-being.
      Search for meaning had both direct and indirect (via negative beliefs about
      alcohol) effects on use and problems. Negative beliefs about alcohol and social
      influences were related to alcohol use via enhancement motives and, in some
      models, social motives for drinking. Spiritual well-being was related to alcohol
      problems via coping motives. Social influences also had direct effects on alcohol
      use. CONCLUSIONS: Although future studies using longitudinal designs are needed,
      the study identified several plausible mechanisms by which
      religiousness/spirituality could causally impact alcohol use and problems.
      Results also provide further support for the motivational model of alcohol use.

PMID- 18080077
TI  - [Medical core competence and delegation in anaesthesia. Resolution of the German
      Society for Anaesthesiology and Intensive Care Medicine and the Professional
      Association of German Anaesthetists from 26.10.2007/08.11.2007].

PMID- 18080078
TI  - [Organ donation].
AB  - For patients with end-stage organ disease transplantation of human organs is a
      well-established therapy, and in most cases it is the only life-saving one. But
      the lack of available organs is a big problem. The legal basis in Germany is the
      transplantation law (TPG). According to this law, every ventilated patient with
      diagnosed brain death is a potential organ donor. However, brain death may lead
      to strong reactions in the patient's cardiovascular system as well as
      disturbances in thermoregulation, water and electrolyte balance, and the
      endocrine and haemostatic systems. Thus, protecting the organs of the organ donor
      and, furthermore, caring for his or her relatives are great challenges for every
      physician and nurse in the intensive care unit.

PMID- 18080080
TI  - Topological estimation biases with covarion evolution.
AB  - Covarion processes allow changes in evolutionary rates at sites along the
      branches of a phylogenetic tree. Covarion-like evolution is increasingly
      recognized as an important mode of protein evolution. Several recent reports
      suggest that maximum likelihood estimation employing covarion models may support
      different optimal topologies than estimation using standard rates-across-sites
      (RAS) models. However, it remains to be demonstrated that ignoring covarion
      evolution will generally result in topological misestimation. In this study we
      performed analytical and theoretical studies of limiting distances under the
      covarion model and four-taxon tree simulations to investigate the extent to which
      the covarion process impacts on phylogenetic estimation. In particular, we
      assessed the limits of an RAS model-based maximum likelihood method to recover
      the phylogenies when the sequence data were simulated under the covarion
      processes. We find that, when ignored, covarion processes can induce systematic
      errors in phylogeny reconstruction. Surprisingly, when sequences are evolved
      under a covarion process but an RAS model is used for estimation, we find that a
      long branch repel bias occurs.

PMID- 18080081
TI  - In vitro induction of 60-kDa and 70-kDa heat shock proteins by endosulphan and
      monocrotophos in sheep blowfly Lucilia cuprina.
AB  - The effect of two most commonly used and highly toxic organic pesticides,
      endosulphan (organochlorine) and monocrotophos (organophosphate), was studied in
      a blowfly, Lucilia cuprina, to test whether these pesticides induce the stress
      response and, if so, whether the intensity of the response, in terms of induction
      of heat shock proteins (HSPs), HSP60 and HSP70 in particular, is pesticide
      concentration dependent. The in vitro exposure of larval and adult tissues to
      varying concentrations of these pesticides (endosulphan: 1.0-4.0 ppm for larva
      and 0.05-0.50 ppm for adult; monocrotophos: 0.0005-0.0050 ppm for larva and
      0.0001-0.0010 ppm for adult) revealed that both compounds were able to induce the
      expression of HSP60 and HSP70 proteins. Western blot analysis of these HSPs
      indicated that the induction of expression was tissue-specific. The trypan blue
      staining of pesticide-exposed tissues demonstrated monocrotophos to exert more
      severe effect than endosulphan, as the former compound induced both HSP60 and
      HSP70 significantly at a much lower concentration than that of the later. The
      pattern of expression of these HSPs, in general, appeared in direct correlation
      with the pesticide concentration. Gut tissues were found relatively more
      sensitive to pesticide toxicity than other tissues, as revealed by trypan blue
      staining, and hence, they might serve as primary targets for early detection of
      pesticide toxicity. The results indicated that either of these HSPs or both could
      serve as a potential biomarker toward assessment and monitoring of toxicity
      induced by these pesticides.

PMID- 18080082
TI  - Heavy metal concentrations in feathers of Korean shorebirds.
AB  - This study presents concentrations of zinc, manganese, copper, lead, and cadmium
      in the feather of five shorebird species from Yeongjong Island, Korea in the East
      Asian-Australian migration flyways. The objectives of this study were to
      determine levels of heavy metal concentrations in the feathers of shorebirds, to
      evaluate the pattern of heavy metal concentrations in the feather and the liver,
      and to examine the correlation between heavy metal concentrations in the feathers
      and livers. We hypothesized that difference of heavy metal concentrations will
      show by the breeding ground of shorebirds. Lead concentrations in dunlins
      (geomean = 14.8 microg/g wet weight) and great knots (20.8 microg/g wet weight)
      feathers were significantly higher than Terek sandpipers (3.32 microg/g wet
      weight); other metals were not different among shorebirds. Zinc, lead, and
      cadmium concentrations in the feather were correlated with the liver
      concentrations, but manganese and copper concentrations were not. Zinc,
      manganese, copper, lead, and cadmium concentrations in the feather from this
      study were within the range of earlier studies for wild birds, but cadmium
      concentrations in dunlins were higher than other studies. Because lead
      concentrations in livers and feathers of the Terek sandpiper were lower than in
      other shorebirds, we suggest that Terek sandpipers were exposed to lower lead
      concentrations than Kentish plovers, dunlins, and great knots on their breeding
      ground.

PMID- 18080085
TI  - Difference in functional outcome of ipsilateral tinnitus after intraoperative
      occurrence of the trigemino-cardiac reflex in surgery for vestibular schwannomas.
AB  - OBJECT: Surgical manipulation of the fifth cranial nerve in its intra- or
      extracranial course may lead to bradycardia or even asystole as well as arterial
      hypotension, a phenomenon described as the trigemino-cardiac reflex (TCR), first
      described by the authors previously [11]. The authors report here the impact of
      this reflex on post-operative ipsilateral tinnitus in patients undergoing
      vestibular schwannoma surgery. METHODS: Thirty six patients scheduled for
      vestibular schwannoma surgery were studied retrospectively for parameters
      influencing the post-operative ipsilateral tinnitus function. According to the
      occurrence of intra- operative TCR the patients were divided into a TCR-subgroup
      and a non-TCR subgroup. There was no difference in tumour size between these
      subgroups. RESULTS: The TCR occurred in 17% of the patients during vestibular
      schwannoma surgery and influenced the occurrence of post-operative ipsilateral
      tinnitus: the overall incidence of post-operative ipsilateral tinnitus was 22%.
      Sixty (60) percent of the patients in the TCR subgroup and 17% of those in the
      non-TCR subgroup experienced ipsilateral tinnitus postoperatively. There was no
      correlation between tinnitus and pre- or post-operative hearing function.
      CONCLUSION: Hypotension after intra-operative TCR is not only a negative
      prognostic factor for hearing preservation but also for ipsilateral tinnitus in
      patients undergoing vestibular schwannoma surgery. In combination with worse
      hearing function after intra-operative TCR, the present finding underlines the
      importance of the TCR during skull base surgery in relation to improved
      functional outcome.

PMID- 18080083
TI  - Regulation of cell-matrix contacts and beta-catenin signaling in VSMC by integrin
      linked kinase: implications for intimal thickening.
AB  - Vascular smooth muscle cell (VSMC) proliferation and migration is responsible for
      intimal thickening that occurs in restenosis and atherosclerosis. Integrin-linked
      kinase (ILK) is a serine/threonine protein kinase implicated in signaling
      pathways involved in cell proliferation and migration. We studied the involvement
      of ILK in intimal thickening. ILK expression was significantly increased in two
      models of intimal thickening: balloon-injured rat carotid arteries and human
      saphenous vein organ cultures. Over-expression of a dominant negative ILK (DN
      ILK) significantly reduced intimal thickening by approximately 50% in human
      saphenous vein organ cultures, demonstrating an important role in intimal
      thickening. ILK protein and activity was reduced on laminin and up-regulated on
      fibronectin, indicating ILK protein expression is modulated by extracellular
      matrix composition. Inhibition of ILK by siRNA knockdown and DN-ILK significantly
      decreased VSMC proliferation and migration while wild type ILK significantly
      increased proliferation and migration on laminin, confirming an essential role of
      ILK in both processes. Localization of paxillin and vinculin and protein levels
      of FAK and phospho-FAK indicated that inhibition of ILK reduced focal adhesion
      formation. Additionally, inhibition of ILK significantly attenuated the presence
      of the cell-cell complex proteins N-cadherin and beta-catenin, and beta-catenin
      signaling. We therefore suggest ILK modulates VSMC proliferation and migration at
      least in part by acting as a molecular scaffold in focal adhesions as well as
      modulating the stability of cell-cell contact proteins and beta-catenin
      signaling. In summary, ILK plays an important role in intimal thickening by
      modulating VSMC proliferation and migration via regulation of cell-matrix and
      cell-cell contacts and beta-catenin signaling.

PMID- 18080084
TI  - Metformin protects the ischemic heart by the Akt-mediated inhibition of
      mitochondrial permeability transition pore opening.
AB  - BACKGROUND: In the majority of studies, metformin has been demonstrated to
      cardioprotect diabetic patients, the mechanism of which is unclear. We
      hypothesized that metformin cardioprotects the ischemic heart through the Akt
      mediated inhibition of mitochondrial permeability transition pore (mPTP) opening.
      MATERIALS AND METHODS: Isolated perfused hearts from normoglycemic Wistar or from
      diabetic Goto-Kakizaki (GK) rats (N > or = 6/group) were subjected to 35 min
      ischemia and 120 min of reperfusion. Metformin (50 micromol/l) was added for 15
      min at reperfusion, alone or with LY294002 (15 micromol/l), a PI3K inhibitor.
      Infarct size and Akt phosphorylation were measured. Furthermore, the effect of
      metformin on mPTP opening in adult cardiomyocytes isolated from both strains was
      determined. RESULTS: Metformin reduced infarct size in both Wistar (35 +/- 2.7%
      metformin vs. 62 +/- 3.0% control: P < 0.05) and GK hearts (43 +/- 4.7% metformin
      vs. 60 +/- 3.8% control: P < 0.05). This protection was accompanied by a
      significant increase in Akt phosphorylation. LY294002 abolished the metformin
      induced Akt phosphorylation and the infarct-limiting effect of metformin in
      Wistar (61 +/- 6.7% metformin + LY294002 vs. 35 +/- 2.7% metformin: P < 0.05) and
      GK rats (56 +/- 5.7% metformin + LY294002 vs. 43 +/- 4.7% metformin: P < 0.05).
      In addition, metformin significantly inhibited mPTP opening and subsequent rigor
      contracture in both Wistar and GK cardiomyocytes subjected to oxidative stress,
      in a LY-sensitive manner. CONCLUSIONS: We report that metformin given at the time
      of reperfusion reduces myocardial infarct size in both the non-diabetic and
      diabetic heart and this protective effect is mediated through PI3K and is
      associated with Akt phosphorylation. Furthermore, cardioprotection appears to be
      executed through a PI3K-mediated inhibition of mPTP opening. These findings may
      explain in part the cardioprotective properties of metformin observed in clinical
      studies of diabetic patients.

PMID- 18080086
TI  - Austronesian genetic signature in East African Madagascar and Polynesia.
AB  - The dispersal of the Austronesian language family from Southeast Asia represents
      the last major diaspora leading to the peopling of Oceania to the East and the
      Indian Ocean to the West. Several theories have been proposed to explain the
      current locations, and the linguistic and cultural diversity of Austronesian
      populations. However, the existing data do not support unequivocally any given
      migrational scenario. In the current study, the genetic profile of 15 autosomal
      STR loci is reported for the first time for two populations from opposite poles
      of the Austronesian range, Madagascar at the West and Tonga to the East. These
      collections are also compared to geographically targeted reference populations of
      Austronesian descent in order to investigate their current relationships and
      potential source population(s) within Southeast Asia. Our results indicate that
      while Madagascar derives 66.3% of its genetic makeup from Africa, a clear
      connection between the East African island and Southeast Asia can be discerned.
      The data suggest that although geographic location has influenced the
      phylogenetic relationships between Austronesian populations, a genetic connection
      that binds them beyond geographical divides is apparent.

PMID- 18080087
TI  - A molecular pin to study the dynamics of beta-barrel formation in pore-forming
      toxins on erythrocytes: a sliding model.
AB  - gamma-Hemolysins are pore-forming toxins which develop from water-soluble
      monomers by combining two different 'albeit homologous' proteins. They form
      oligomeric pores in both cell and model membranes by undergoing a still poorly
      understood conformational rearrangement in the stem region. The stem is formed by
      three beta-strands, folded onto the core of the soluble protein and completely
      extended in the pore. We propose a new model to explain such a process. Seven
      double-cysteine mutants were developed by inserting one cysteine on the stretch
      that links the beta-hairpin to the core of the protein and another on different
      positions along the beta-strands. The membrane bound protein was blocked in a non
      lytic state by S-S bond formation. Six mutants were oxidized as inactive
      intermediates, but became active after adding DTT. These results demonstrate that
      the stem extension can be temporarily frozen and that the beta-barrel formation
      occurs by beta-strand concerted step-by-step sliding.

PMID- 18080088
TI  - The interface of protein-protein complexes: analysis of contacts and prediction
      of interactions.
AB  - Specific protein-protein interactions are essential for cellular functions.
      Experimentally determined three-dimensional structures of protein-protein
      complexes offer the possibility to characterize binding interfaces in terms of
      size, shape and packing density. Comparison with crystal-packing interfaces
      representing nonspecific protein-protein contacts gives insight into how specific
      binding differs from nonspecific low-affinity binding. An overview is given on
      empirical structural rules for specific protein-protein recognition derived from
      known complex structures. Although single parameters such as interface size,
      shape or surface complementary show clear trends for different interface types,
      each parameter alone is insufficient to fully distinguish between specific versus
      crystal-packing contacts. A combination of interface parameters is, however, well
      suited to characterize a specific interface. This knowledge provides us with the
      essential ingredients that make up a specific protein recognition site. It is
      also of great value for the prediction of protein binding sites and for the
      evaluation of predicted complex structures.

PMID- 18080089
TI  - Role of serotonin in the hepato-gastroIntestinal tract: an old molecule for new
      perspectives.
AB  - Beside its role as a neurotransmitter in the central nervous system, serotonin
      appears to be a central physiologic mediator of many gastrointestinal (GI)
      functions and a mediator of the brain-gut connection. By acting directly and via
      modulation of the enteric nervous system, serotonin has numerous effects on the
      GI tract. The main gut disturbances in which serotonin is involved are acute
      chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel
      syndrome. Serotonin also has mitogenic properties. Platelet-derived serotonin is
      involved in liver regeneration after partial hepatectomy. In diseased liver,
      serotonin may play a crucial role in the progression of hepatic fibrosis and the
      pathogenesis of steatohepatitis. Better understanding of the role of the
      serotonin receptor subtypes and serotonin mechanisms of action in the liver and
      gut may open new therapeutic strategies in hepato-gastrointestinal diseases.

PMID- 18080090
TI  - Prognostic factors in breast cancer patients with brain metastases.

PMID- 18080091
TI  - High glucose induced human umbilical vein endothelial cell injury: involvement of
      protein tyrosine nitration.
AB  - The dysfunction and further damage of endothelium play an important role in the
      development and progression of diabetic vascular complications. Protein tyrosine
      nitration is involved in endothelial cell injury induced by high glucose. Little
      is known about protein nitration in human umbilical vein endothelial cells
      (ECV304) induced by high glucose. In the present article, exposure of ECV304 to
      30 mM high glucose (HG30) and 40 mM high glucose (HG40) or hemin-nitrite-H2O2
      system for 72 h, the cell injury in ECV304 induced by high glucose and exogenous
      nitrating agent was studied. After 72 h treatment, it was found that high glucose
      stimulated ECV304 injury in a dose-dependent manner, including reducing cell
      viability, increasing malondialdehyde (MDA) content, decreasing glutathione (GSH)
      content, increasing intracellular reactive oxygen species (ROS), increasing the
      production of nitric oxygen (NO) (increased nitrite content in cell and nitrate
      content in medium) and generating protein tyrosine nitration. It was also found
      that protein tyrosine nitration could induce cell injury further. By comparison
      the protein tyrosine nitration induced by high glucose condition and extrinsic
      factors (hemin-nitrite-H2O2 system), it may be speculated that protein is
      nitrated selectively to generate nitrotyrosine in diabetic vascular
      complications.

PMID- 18080092
TI  - Gymnemic acid interacts with mammalian glycerol-3-phosphate dehydrogenase.
AB  - In a previous study, we found interaction of gymnemic acid (GA) with
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis. We
      now examined interaction of GA with glycolytic and related enzymes. We found that
      (1) GA induced a band smearing of glycerol-3-phosphate dehydrogenase (G3PDH) as
      well as that of GAPDH in SDS-PAGE, (2) GA diminished the G3PDH band detected by
      an antibody to phosphoserine, and (3) GA inhibited the G3PDH activity. The GA
      induced smearing of the G3PDH band was diminished by prior incubation of GA with
      gamma-cyclodextrin. GA gave no effects on the electrophoretic and phosphoserine
      bands of other glycolytic enzymes. NAD and NADH diminished the GA-induced
      smearing of the G3PDH and GAPDH bands in different concentration-dependent
      manner. Pretreatment of G3PDH with heated SDS-containing buffer or pretreatment
      with hydroxylamine diminished the GA-induced smearing of G3PDH. Deacylation of GA
      by alkaline hydrolysis diminished the smearing of G3PDH band, thereby indicating
      that the acyl moieties of GA were necessary for the GA-induced smearing of G3PDH.
      These results indicated the interaction of GA with G3PDH, an enzyme involved in
      glycerol metabolism. These studies suggest that GA may have some pharmacological
      activities including antidiabetic activity and lipid lowering effects via
      interaction with GAPDH and G3PDH.

PMID- 18080093
TI  - Mycophenolate mofetil therapy in uveitis: analysis of eight cases in a tertiary
      ophthalmic care centre in India.
AB  - Mycophenolate mofetil (MMF) is a relatively new immunomodulatory agent. The
      experience of MMF in inflammatory eye diseases is limited to a few case series.
      We report our experience of MMF in eight patients with uveitis. Control of
      inflammation was achieved in all patients. No patient had adverse side effects.
      Our study indicates that MMF is a safe and effective immunomodulatory agent.

PMID- 18080094
TI  - Long-term refractive stability following combined astigmatic keratotomy and
      phakoemulsification.
AB  - BACKGROUND: To determine whether combined astigmatic keratotomy and cataract
      surgery induces a sustained reduction in astigmatism. METHODS: Patients who had
      previously undergone combined cataract surgery and astigmatic keratotomy for
      naturally occurring astigmatism were identified and their notes reviewed. Mean
      final follow-up was 34 months (30-42 months). Fourteen eyes of 11 patients were
      eligible for study. Arcuate corneal incisions had been employed using the Buzard
      nomogram. Using power vector analysis, the post-operative refractive change at 6
      months and final follow-up was determined. RESULTS: The mean preoperative
      manifest cylindrical refractive error was 2.88 D (1.50-5.50 D). The mean
      postoperative manifest cylindrical refractive error was 1.89 and 1.79 D at 6
      months and final follow-up, respectively. Power vector analysis demonstrated a
      significant postoperative reduction in refractive blur at 6 months and final
      follow-up (P = 0.006, P = 0.004, respectively): mean preoperative blur strength
      was 2.90 D and mean postoperative blur strength was 1.33 and 1.25 D at 6 months
      and final follow-up, respectively. Sustained postoperative reduction in
      astigmatism was noted in 12 of 14 eyes at final follow-up. CONCLUSIONS:
      Astigmatic keratotomy is a well-established treatment for astigmatism. In this
      series, the refractive benefit from combined astigmatic keratotomy and cataract
      surgery is maintained for several years. No surgical complications were observed.

PMID- 18080095
TI  - The value of chemical fat-saturation pulse added to T1-weighted spin-echo
      sequence in evaluating gadolinium-enhancing brain lesions in multiple sclerosis.
AB  - PURPOSE: This study was undertaken to assess the value of a chemical (spectral)
      fat-saturation (fat-sat) pulse added to a T1-weighted spin-echo sequence after
      intravenous administration of paramagnetic contrast agent in detecting enhancing
      lesions in multiple sclerosis. MATERIALS AND METHODS: Twenty patients with
      relapsing-remitting multiple sclerosis underwent a brain 1.0-Tesla magnetic
      resonance (MR) scan with T1-weighted spin-echo sequences (24 contiguous para
      axial slices with a thickness of 5 mm, pixel size 0.96 mm(2), number of
      excitations 2, flip angle 90 degrees ) 5 min after intravenous injection of 0.1
      mmol/kg of gadodiamide with and without fat-sat, acquired with randomised order
      of priority. Two readers counted by consensus the number of enhancing lesions and
      assigned a conspicuity score (low conspicuity=1; high conspicuity=2) to each
      enhancing lesion during a randomised reading without any visual comparison
      between the two corresponding images (with and without fat-sat) of the same
      patient. McNemar and Wilcoxon matched-pair signed-rank tests were used. RESULTS:
      Seventy-two enhancing lesions without fat-sat and 94 with fat-sat were detected;
      22 lesions were visible only with fat-sat, whereas no lesion was detected only
      without fat-sat (p<0.0001). The conspicuity score was 1.17+/-0.38 (mean+/
      standard deviation) and 1.57+/-0.44, respectively (p<0.0001). CONCLUSIONS: A fat
      sat pulse added to a T1-weighted spin-echo sequence increases significantly the
      number and conspicuity of contrast-enhancing lesions in patients with relapsing
      remitting multiple sclerosis.

PMID- 18080096
TI  - Digital cineradiographic study of swallowing in patients with amyotrophic lateral
      sclerosis.
AB  - PURPOSE: This study was performed to evaluate the usefulness of digital
      cineradiography in detecting swallowing disorders in dysphagic patients affected
      by amyotrophic lateral sclerosis (ALS) with a view to planning an adequate
      therapeutic approach. MATERIAL AND METHODS: From January 2005 to September 2006,
      23 patients (10 men and 13 women; mean age 41.3+/-8.6 years) affected by ALS were
      evaluated with digital cineradiography to assess the grade of dysphagia. All
      patients were classified using the Hillel ALS Severity Scale (ALSSS). All
      examinations were performed with radiocontrolled equipment provided with a
      digital C-arm. RESULTS: The cineradiographic technique enabled us to
      differentiate patients with disorders of the oral (17/23) and/or pharyngeal
      (19/23) swallowing phase from those without swallowing dysfunction (4/23). In
      14/23 patients, passage of contrast medium into the upper airways was observed
      during swallowing, whereas in 5/23 cases, aspiration of contrast medium into the
      lower airways was recorded. CONCLUSIONS: The videofluoroscopic swallowing study
      has high diagnostic capabilities in the evaluation of swallowing disorders, as it
      is able to identify the degree and causes of impairment. In addition, the study
      proved useful for planning speech therapy and for follow-up in patients with ALS.

PMID- 18080097
TI  - Coronary variants and anomalies: methodology of visualisation with 64-slice CT
      and prevalence in 202 consecutive patients.
AB  - PURPOSE: This paper aims to provide the tools for a complete anatomical
      evaluation of the coronary tree using 64-slice computed tomography (CT) and
      evaluate the prevalence of anatomical variants and anomalies in a population of
      202 consecutive patients. MATERIALS AND METHODS: Two hundred and two patients
      with suspected coronary artery disease underwent 64-slice CT with a standard
      protocol. Two observers working in consensus evaluated and collected the data
      regarding anatomical variants and anomalies of the coronary vessels. RESULTS: In
      the 202 consecutive patients, the prevalence of anatomical variants was: left
      dominant circulation (7%), absent left main (5%), presence of intermediate branch
      (17%), aortic origin of conus branch (13%) and circumflex origin of sinus node
      branch (15%). Coronary anomalies (origin and course, intrinsic and termination)
      showed an overall prevalence of 25%. CONCLUSIONS: CT is the ideal method for the
      three-dimensional evaluation of the coronary tree. Anatomical variants and
      anomalies of the coronary arteries are quite common and should be known and
      recognised promptly by the operators.

PMID- 18080098
TI  - Imaging of myocardial infarction using a 64-slice MDCT scanner: correlation
      between infarcted region and status of territory-dependent coronary artery.
AB  - PURPOSE: This study was performed to evaluate the ability of 64-slice
      multidetector computed tomography (MDCT) to detect previous myocardial
      infarctions (MIs) in patients referred for the assessment of the coronary
      arteries. In patients with regional changes of left ventricular wall myocardial
      density, the territory-dependent coronary vessel status was examined. MATERIALS
      AND METHODS: We retrospectively assessed 202 consecutive patients referred for 64
      slice MDCT of the coronary arteries. In all cases, detailed, clinical,
      serological and electrocardiograph (ECG) data were collected to identify patients
      with a previous diagnosis of MI. An initial qualitative evaluation of MDCT images
      was performed in all patients to identify areas of suspected myocardial necrosis,
      which were defined as regions of lower density within normally enhanced left
      ventricular myocardium. Thereafter, in all patients with suspected MIs,
      attenuation values and left ventricular wall thickness were also measured at the
      level of the normal myocardium and within the hypodense regions. Each MI was also
      assigned to the distribution territory of a coronary vessel, and morphological
      data were combined with MDCT angiographic findings. RESULTS: After clinical
      assessment, MI was found in 27 patients (six acute).; 64-slice MDCT was able to
      detect the presence of MI in 24/27 cases, showing sensitivity and specificity of
      89% and 95%, respectively, and an overall diagnostic accuracy of 95%.
      Quantitative analysis showed a significant difference (p<0.01) between
      attenuation values of normal vs. infarcted myocardium (124.5+/-19 HU vs. 56.1+/
      23 HU, respectively); wall thinning was exclusively observed in chronic MIs
      (p<0.01). In 23/24 detected cases, analysis of territory-dependent arteries
      showed findings compatible with presence of MI. CONCLUSIONS: The presence of MI
      is well depicted with retrospective 64-slice MDCT. The main advantage of 64-slice
      MDCT is that it allows to evaluate and relate the status of a vessel and its
      dependent myocardial region in a single exam.

PMID- 18080099
TI  - Venous sinus thrombosis: a misdiagnosis using MR angiography.
AB  - INTRODUCTION: Magnetic resonance venography (MRV) is a non-invasive imaging
      modality that is used in many centers to supplant conventional cerebral digital
      subtraction angiography (DSA) for the diagnosis of dural venous sinus thrombosis.
      DISCUSSION: We present the case of a pregnant female diagnosed with dural venous
      sinus thrombosis by serial time-of-flight (TOF) MRV examinations, and treated
      with long-term anticoagulation based on these examinations. RESULTS: The
      appearance of the affected dural sinus did not change on MRV over the treatment
      period. The patient returned during follow-up with new-onset pulsatile tinnitus,
      which prompted us to perform DSA to exclude a dural arteriovenous fistula. DSA
      revealed that the segment of venous sinus diagnosed as thrombosed on MRV actually
      was patent but had a septation in its midsection. CONCLUSIONS: We concluded that
      the patient did not have a venous sinus thrombosis at the time of MRV
      examinations but rather an anatomical variant mimicking a thrombosis, which would
      not have required any treatment. MRV, particularly TOF MRV, is limited by
      artifacts in correctly identifying vascular anatomy and pathology and should be
      interpreted carefully. DSA remains the reference standard for most vascular
      imaging.

PMID- 18080100
TI  - Leptin regulates chondrogenic differentiation in ATDC5 cell-line through JAK/STAT
      and MAPK pathways.
AB  - Leptin, the satiety hormone, has been found to affect growth-plate cartilage
      development. In the present study, some of the signal transduction pathways that
      mediate leptin signaling in the ATDC5 chondrogenic cell-line, a model for
      endochondral ossification, were analyzed. For this purpose, real-time PCR,
      Western blots and immunofluorescence techniques were used. It was found that
      leptin increased phosphorylation of ERK1/2, p38, and STAT3 in a time- and dose
      dependent manner. Specific inhibition of STAT3 or ERK1/2, but not of P38, blocked
      the stimulatory effect of leptin on type X collagen mRNA levels. Moreover, leptin
      induced the translocation of ERK1/2 into the nucleus, as well as c-fos
      expression, indicating full activation of this cascade. Leptin-induced JNK
      phosphorylation was not observed, although leptin significantly and rapidly
      increased JNK protein levels and c-jun mRNA levels. In addition, ERK5 was
      identified in these cells, but there was no apparent effect of leptin on either
      its phosphorylation or protein level. The study indicates that the effects of
      leptin on growth-plate chondrocytes are specifically mediated through ERK1/2 and
      STAT3, while P38 is not essential for leptin-induced type X collagen expression.
      This is the first demonstration that these pathways are involved in leptin
      induced growth.

PMID- 18080101
TI  - What you think you know can hurt you: perceptual biases about HIV risk in
      intimate relationships.
AB  - The use of heuristic biases and the false consensus effect can lead individuals
      to misperceive risk of HIV infection. The current paper presents the results of
      two studies which sought to examine whether individuals, (a) weigh risk relevant
      information accurately in their assessments of HIV risk, and (b) are susceptible
      to the false consensus effect in their assessments of actual intimate partner
      risk behaviors. The results of the first study support the hypothesis that
      individuals do not use objective risk information based on probability statistics
      in their assessments of HIV risk. In addition, the results of the second study
      find that female partners exhibit the false consensus effect regarding sexual
      risk behaviors, whereas male partners did not. Discussion centers on the role of
      perceptual biases in HIV risk behaviors among individuals in intimate
      relationships.

PMID- 18080102
TI  - [The phenomenon of depth of anaesthesia].

PMID- 18080104
TI  - [Accidental intravascular bupivacaine administration].

PMID- 18080105
TI  - CCN2, the connective tissue growth factor.

PMID- 18080106
TI  - Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in
      persons with impaired fasting glucose and/or impaired glucose tolerance in the
      EUGENE2 study.
AB  - AIMS/HYPOTHESIS: We examined the phenotype of individuals with impaired fasting
      glucose (IFG) and/or impaired glucose tolerance (IGT) with regard to insulin
      release and insulin resistance. METHODS: Non-diabetic offspring (n=874; mean age
      40+/-10.4 years; BMI 26.6+/-4.9 kg/m(2)) of type 2 diabetic patients from five
      different European Centres (Denmark, Finland, Germany, Italy and Sweden) were
      examined with regard to insulin sensitivity (euglycaemic clamps), insulin release
      (IVGTT) and glucose tolerance (OGTT). The levels of glucagon-like peptide-1 (GLP
      1) and gastric inhibitory polypeptide (GIP) were measured during the OGTT in 278
      individuals. RESULTS: Normal glucose tolerance was found in 634 participants,
      while 110 had isolated IFG, 86 had isolated IGT and 44 had both IFG and IGT, i.e.
      about 28% had a form of reduced glucose tolerance. Participants with isolated IFG
      had lower glucose-corrected first-phase (0-10 min) and higher second-phase
      insulin release (10-60 min) during the IVGTT, while insulin sensitivity was
      reduced in all groups with abnormal glucose tolerance. Similarly, GLP-1 but not
      GIP levels were reduced in individuals with abnormal glucose tolerance.
      CONCLUSIONS/INTERPRETATION: The primary mechanism leading to hyperglycaemia in
      participants with isolated IFG is likely to be impaired basal and first-phase
      insulin secretion, whereas in isolated IGT the primary mechanism leading to
      postglucose load hyperglycaemia is insulin resistance. Reduced GLP-1 levels were
      seen in all groups with abnormal glucose tolerance and were unrelated to the
      insulin release pattern during an IVGTT.

PMID- 18080107
TI  - Loss of 50% of excess weight using a very low energy diet improves insulin
      stimulated glucose disposal and skeletal muscle insulin signalling in obese
      insulin-treated type 2 diabetic patients.
AB  - AIMS/HYPOTHESIS: Both energy restriction (ER) per se and weight loss improve
      glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term
      ER decreases basal endogenous glucose production (EGP) but not glucose disposal.
      In contrast the blood glucose-lowering mechanism of long-term ER with substantial
      weight loss has not been fully elucidated. The aim of this study was to
      investigate the effect of loss of 50% of excess weight [50% excess weight
      reduction (EWR)] on EGP, whole-body insulin sensitivity and the disturbed
      myocellular insulin-signalling pathway in ten obese insulin-treated type 2
      diabetic patients. METHODS: A euglycaemic-hyperinsulinaemic clamp with stable
      isotopes ([6,6-(2)H2]glucose and [2H5]glycerol) combined with skeletal muscle
      biopsies was performed during a very low energy diet (VLED; 1,883 kJ/day) on day
      2 and again after 50% EWR. Oral blood glucose-lowering agents and insulin were
      discontinued 3 weeks prior to the VLED and at the start of the VLED,
      respectively. RESULTS: Loss of 50% EWR (20.3+/-2.2 kg from day 2 to day of 50%
      EWR) normalised basal EGP and improved insulin sensitivity, especially insulin
      stimulated glucose disposal (18.8+/-2.0 to 39.1+/-2.8 micromol kg fat-free mass(
      1) min(-1), p=0.001). The latter was accompanied by improved insulin signalling
      at the level of the recently discovered protein kinase B/Akt substrates AS160 and
      PRAS40 along with a decrease in intramyocellular lipid (IMCL) content.
      CONCLUSIONS/INTERPRETATION: Considerable weight loss in obese, insulin-treated
      type 2 diabetic patients normalises basal EGP and improves insulin sensitivity
      resulting from an improvement in insulin signal transduction in skeletal muscle.
      The decrease in IMCL might contribute to this effect.

PMID- 18080108
TI  - [Spinal problems in persons with skeletal dysplasias].
AB  - Most skeletal dysplasias are characterized by small stature. Less well known is
      the fact that most skeletal dysplasias are also associated with specific spinal
      problems or deformities. This article summarizes the various aspects of spinal
      problems in this patient population as well as the diagnostic strategies and
      current and new treatment options.

PMID- 18080109
TI  - [Hyperphosphatasia and hypophosphatasia in childhood].
AB  - The treatment of phosphate diabetes and hyperphosphatasia requires an
      interdisciplinary therapy concept between paediatricians and orthopaedic
      surgeons. The surgical challenge is the correction of the multiplanar bending
      deformities and the pathological fractures. Different techniques are discussed in
      the literature without an outstanding recommendation for a special approach. This
      contribution gives an overview of the published methods and discusses various
      surgical concepts in view of our own clinical experience.

PMID- 18080110
TI  - Prohormones: novel biomarkers for corticosteroids in septic shock?

PMID- 18080111
TI  - The influence of corticosteroids on the release of novel biomarkers in human
      endotoxemia.
AB  - OBJECTIVE: Sepsis intervention studies need better patient stratification
      methods, and one way to realize this is the introduction of stable biomarkers. A
      set of recently developed novel biomarkers, based upon precursor-fragments of
      short-lived hormones, was previously shown to be increased during sepsis.
      However, it is not known whether these biomarkers are influenced by sepsis
      intervention strategies. Therefore we investigated the markers in a model of
      human endotoxemia intervened by increasing doses of prednisolone. DESIGN AND
      SETTING: Prospective, open-label study in a specialized clinical research unit of
      a university hospital. SUBJECTS: Thirty-two healthy male volunteers.
      INTERVENTIONS: Subjects received prednisolone orally at doses of 0, 3, 10 or 30
      mg (n=8 per group) at 2 h before intravenous injection of Escherichia coli
      lipopolysaccharide (LPS) (4 ng/kg). Blood samples were drawn during 24 h after
      LPS injection. MEASUREMENTS AND RESULTS: LPS injection caused an increase in
      levels of midregional pro-adrenomedullin (MR-proADM), midregional pro-atrial
      natriuretic peptide (MR-proANP), C-terminal pro-arginine-vasopressin (CT-proAVP)
      and procalcitonin (PCT). Prednisolone caused a dose dependent inhibition of MR
      proADM, MR-proANP and CT-proAVP levels. CONCLUSIONS: These results show that a
      set of novel, highly stable sepsis biomarkers was increased during human
      endotoxemia and was dose-dependently inhibited by corticosteroid pre-treatment.

PMID- 18080112
TI  - The influence of the lower patellar pole in the pathogenesis of chronic patellar
      tendinopathy.
AB  - Resection of the lower patellar pole provides good results in the treatment of
      jumper's knee. Therefore we hypothesized that the length of the lower patellar
      pole is increased in patients with chronic patellar tendinopathy. Cohort study,
      level of evidence 2. Between 2000 and 2005, 25 patients with chronic patellar
      tendinopathy underwent conservative and surgical treatment in our clinic. All of
      them had preoperative MRI were three independent examiners measured the Caton
      Index, the length and the ratio of the articular and non-articular patellar
      surface, tendon length and thickness and the thickness and length of the hypodens
      lesions in the patellar tendon. The measurements were compared with 50 MRI of a
      control group with no clinical patellofemoral disorders or patellar tendinopathy.
      Significant changes in tendon thickness (9.42+/-2.87 vs. 4.88+/-1.13; P<0.0001),
      a longer non-articular surface of the patella (10.62+/-2.86 vs. 7.098+/-2.53;
      P<0.0001) and significant higher ratio between the articular and the non
      articular patellar surface (0.32 vs. 0.24; P<0.0001) were found in the jumper's
      knee group. No significant changes were seen in the length of the articular
      surface or the Caton Index. The development of chronic patellar tendinopathy in
      athletes might be associated with a longer lower patellar pole as patients with
      jumper's knee showed a longer non-articular patellar surface compared with the
      control group.

PMID- 18080113
TI  - Biosynthesis of rubradirin as an ansamycin antibiotic from Streptomyces
      achromogenes var. rubradiris NRRL3061.
AB  - The four overlapping cosmids from the rubradirin producer, Streptomyces
      achromogenes var rubradiris NRRL 3061, have 58 ORFs within a 105.6 kb fragment.
      These ORFs harbored essential genes responsible for the formation and attachment
      of four distinct moieties, along with the genes associated with regulatory,
      resistance, and transport functions. The PKS (rubA) and glycosyltransferase
      (rubG2) genes were disrupted in order to demonstrate a complete elimination of
      rubradirin production. The rubradirin biosynthetic pathway was proposed based on
      the putative functions of the gene products, the functional identification of
      sugar genes, and the mutant strains.

PMID- 18080114
TI  - Heightened aggression after chronic flunitrazepam in male rats: potential links
      to cortical and caudate-putamen-binding sites.
AB  - RATIONALE: Higher doses of benzodiazepines induce sedation. However, in low to
      moderate doses, benzodiazepines can increase aggressive behavior both after acute
      and chronic administration. The determinants for increasing aggression after
      chronic intake of flunitrazepam, a so-called date rape drug, in violence-prone
      individuals are incompletely understood. OBJECTIVES: The aim of this study is to
      assess the effects of acute and chronic treatment with flunitrazepam on male
      aggression in resident rats. We also examined possible changes in binding to
      benzodiazepine receptors throughout the brain of rats that display aggressive
      behavior after repeated flunitrazepam treatment using quantitative receptor
      autoradiography. MATERIALS AND METHODS: The behaviors of the male Wistar resident
      rats (n = 35) toward a male intruder were recorded for 10 min twice a week. The
      salient aggressive and non-aggressive elements in the resident rat's behavior
      were analyzed. Initially, the dose-dependent effects of flunitrazepam (0.01,
      0.03, 0.1, 0.18, and 0.3 mg/kg) or vehicle were determined in all rats;
      subsequently, 0.3 mg/kg per day flunitrazepam was administered for 42 days (n =
      15), and a parallel group was treated with vehicle (n = 20). After the chronic
      treatment, the flunitrazepam (0, 0.01, 0.03, 0.1, 0.18, and 0.3 mg/kg) effects
      were again assessed. RESULTS: The most significant finding is the escalation of
      aggression after chronic treatment with flunitrazepam. A previously sedative 0.3
      mg/kg dose of flunitrazepam engendered very high levels of attack bites, sideways
      threats, and aggressive postures (total aggression) after 6 weeks of daily
      administration. Individual differences emerged, and these were associated with
      decreased binding to benzodiazepine receptors, mainly in the limbic structures
      such as the cingulate cortex (cingulate areas 1 and 2) and caudate-putamen
      (posterior part) of aggressive animals, suggesting that these areas are pivotal
      in the control of emotional and aggressive behavior. CONCLUSIONS: Chronic
      flunitrazepam produces changes in receptor binding in discrete areas of the
      cingulate cortex and caudate-putamen that are proposed to be part of the
      mechanisms for increased expression of aggressive behavior.

PMID- 18080116
TI  - Experiences at a small startup.

PMID- 18080115
TI  - Repeated amphetamine administration induces Fos in prefrontal cortical neurons
      that project to the lateral hypothalamus but not the nucleus accumbens or
      basolateral amygdala.
AB  - RATIONALE: The development of sensitization to amphetamine (AMPH) is dependent on
      increases in excitatory outflow from the medial prefrontal cortex (mPFC) to
      subcortical centers. These projections are clearly important for the progressive
      enhancement of the behavioral response during drug administration that persists
      through withdrawal. OBJECTIVES: The objective of this study was to identify the
      mPFC subcortical pathway(s) activated by a sensitizing regimen of AMPH. MATERIALS
      AND METHODS: Using retrograde labeling techniques, Fos activation was evaluated
      in the predominant projection pathways of the mPFC of sensitized rats after a
      challenge injection of AMPH. RESULTS: There was a significant increase in Fos
      immunoreactive cells in the mPFC, nucleus accumbens (NAc), basolateral amygdala
      (BLA), and lateral hypothalamus (LH) of rats treated repeatedly with AMPH when
      compared to vehicle-treated controls. The mPFC pyramidal neurons that project to
      the LH but not the NAc or BLA show a significant induction of Fos after repeated
      AMPH treatment. In addition, we found a dramatic increase in Fos-activated orexin
      neurons. CONCLUSIONS: The LH, a region implicated in natural and drug reward
      processes, may play a role in the development and persistence of sensitization to
      repeated AMPH through its connections with the mPFC and possibly through its
      orexin neurons.

PMID- 18080117
TI  - Preparation of beta-caryophyllene oxidation products and their determination in
      ambient aerosol samples.
AB  - Oxidation of beta-caryophyllene with ozone followed by reduction was carried out
      in dichloromethane. Reaction led to the formation of beta-caryophyllene aldehyde
      (11%, purity 90.8%) and beta-nocaryophyllone aldehyde (79%, purity 99%).
      Compounds were purified and separated by liquid-liquid extraction and flash
      chromatography. Identifications were achieved by electron-impact and electrospray
      ionization mass spectrometry, and precise structures were confirmed by one and
      two-dimensional nuclear magnetic resonance spectroscopy. The prepared compounds
      were used in the analysis of ambient aerosol samples collected during spring 2003
      at Hyytiala, Finland. beta-Nocaryophyllone aldehyde was positively identified and
      quantified in ambient aerosol samples for the first time. The amount of
      quantified beta-nocaryophyllone aldehyde of aerosol origin was 17.4 +/- 1.0 ng m(
      3) of sampled air. Comparison with previous findings led to the conclusion that
      oxidation products of beta-caryophyllene participate in biogenic aerosol
      formation over boreal forest during late spring.

PMID- 18080118
TI  - Problems in obtaining precise and accurate Sr isotope analysis from geological
      materials using laser ablation MC-ICPMS.
AB  - This paper reviews the problems encountered in eleven studies of Sr isotope
      analysis using laser ablation multicollector inductively coupled plasma mass
      spectrometry (LA-MC-ICPMS) in the period 1995-2006. This technique has been shown
      to have great potential, but the accuracy and precision are limited by: (1) large
      instrumental mass discrimination, (2) laser-induced isotopic and elemental
      fractionations and (3) molecular interferences. The most important isobaric
      interferences are Kr and Rb, whereas Ca dimer/argides and doubly charged rare
      earth elements (REE) are limited to sample materials which contain substantial
      amounts of these elements. With modern laser (193 nm) and MC-ICPMS equipment,
      minerals with >500 ppm Sr content can be analysed with a precision of better than
      100 ppm and a spatial resolution (spot size) of approximately 100 microm. The LA
      MC-ICPMS analysis of 87Sr/86Sr of both carbonate material and plagioclase is
      successful in all reported studies, although the higher 84Sr/86Sr ratios do
      suggest in some cases an influence of Ca dimer and/or argides. High Rb/Sr (>0.01)
      materials have been successfully analysed by carefully measuring the 85Rb/87Rb in
      standard material and by applying the standard-sample bracketing method for
      accurate Rb corrections. However, published LA-MC-ICPMS data on clinopyroxene,
      apatite and sphene records differences when compared with 87Sr/86Sr measured by
      thermal ionisation mass spectrometry (TIMS) and solution MC-ICPMS. This suggests
      that further studies are required to ensure that the most optimal correction
      methods are applied for all isobaric interferences.

PMID- 18080119
TI  - Direct eicosanoid profiling of the hypoxic lung by comprehensive analysis via
      capillary liquid chromatography with dual online photodiode-array and tandem mass
      spectrometric detection.
AB  - Eicosanoids are arachidonic acid-derived mediators, with partly contradictory,
      incompletely elucidated actions. Thus, epoxyeicosatrienoic acids (EETs) are
      controversially discussed as putative vasodilatative endothelium-derived
      hyperpolarizing factors in the cardiovascular compartment but reported as
      vasoconstrictors in the lung. Inconsistent findings concerning eicosanoid
      physiology may be because previous methods were lacking sensitivity,
      identification reliability, and/or have focused on special eicosanoid groups
      only, ignoring the overall mediator context, and thus limiting the correlation
      accuracy between autacoid formation and bioactivity profile. Therefore, we
      developed an approach which enables the simultaneous assessment of 44
      eicosanoids, including all representatives of the arachidonic acid cascade, i.e.,
      cytochrome P450, lipoxygenase, cyclooxygenase products, and free isoprostanes as
      in vivo markers of oxidative stress, in one 50-minute chromatographic run. The
      approach combines (i) source-specific sample extraction, (ii) rugged isocratic
      and high-sensitivity capillary liquid-chromatographic separation, and (iii)
      reliable dual online photodiode-array and electrospray ionization tandem mass
      spectrometric identification and quantitation. High sensitivity with limits of
      quantification in the femtogram range was achieved by use of capillary columns
      with typical high peak efficiency, due to small inner diameters, and virtually
      complete substance transfer to the mass spectrometer, due to flow rates in the
      low microliter range, instead of large inner diameter columns with low
      chromatographic signal and only partial analyte transfer employed by previous
      methods. This expeditious, global and sensitive technique provides the
      prerequisite for new, accurate insights regarding the physiology of specific
      mediators, for example EETs, in the context of all relevant vasoactive autacoids
      under varying conditions of oxidative stress by direct comparison of all
      eicosanoid generation profiles. Indeed, application of comprehensive
      "eicoprofiling" to hypoxically ventilated rabbit lungs revealed at a glance the
      enhanced biosynthesis of free EETs in the overall mediator generation context,
      thus suggesting their hypothetical contribution to hypoxic pulmonary
      vasoconstriction.

PMID- 18080120
TI  - High-level expression of a truncated 1,3-1,4-beta-D-glucanase from Fibrobacter
      succinogenes in Pichia pastoris by optimization of codons and fermentation.
AB  - 1,3-1,4-beta-D-glucanase is an important endoglycosidase in the brewing and
      animal feed industries. To achieve high-level expression of recombinant glucanase
      in Pichia pastoris, we designed sequences encoding the alpha-factor signal
      peptide from Saccharomyces cerevisiae and the truncated 1,3-1,4-beta-D-glucanase
      from Fibrobacter succinogenes as a whole. The codons encoding the 52 amino acids
      of the signal peptide and 106 residues of the glucanase protein were optimized
      for expression in P. pastoris; 189 nucleotides were changed. The G + C content
      was adjusted to 48-49%, and AT-rich stretches were eliminated to avoid premature
      termination. The messenger ribonucleic acid secondary structure near the AUG
      start codon was also adjusted to ensure efficient translation; the resulting
      glucanase production was twofold higher compared with that achieved with gene
      structure optimization alone. We also propose a new fermentation strategy for the
      induction phase, in which 5/95% glycerol/methanol mixed feed was used in days 1-3
      and 100% methanol was used on days 4-6. By comparison with methanol feed and
      glycerol/methanol-mixed feed alone, the yield of recombinant glucanase increased
      by 38.5 and 16.5%, respectively. The expressed optimized recombinant 1,3-1,4-beta
      D-glucanase constituted approximately 90% of the total secreted protein, reaching
      up to 3 g l(-1) in the medium.

PMID- 18080121
TI  - Electricity generation by thermophilic microorganisms from marine sediment.
AB  - The search for microorganisms that are capable of catalyzing the reduction of an
      electrode within a fuel cell has primarily been focused on bacteria that operate
      mesobiotically. Bacteria that function optimally under extreme conditions are
      beginning to be examined because they may serve as more effective catalysts
      (higher activity, greater stability, longer life, capable of utilizing a broader
      range of fuels) in microbial fuel cells. An examination of marine sediment from
      temperate waters (Charleston, SC) proved to be a good source of thermophilic
      electrode-reducing bacteria. Electric current normalized to the surface area of
      graphite electrodes was approximately ten times greater when sediment fuel cells
      were incubated at 60 degrees C (209 to 254 mA/m(2)) vs 22 degrees C (10 to 22
      mA/m(2)). Electricity-generating communities were selected in sediment fuel cells
      and then maintained without sediment or synthetic electron-carrying mediators in
      single-chambered fuel cells. Current was generated when cellulose or acetate was
      added as a substrate to the cells. The 16S ribosomal ribonucleic acid genes from
      the heavy biofilms that formed on the graphite anodes of acetate-fed fuel cells
      were cloned and sequenced. The preponderance of the clones (54 of 80) was most
      related to a Gram-positive thermophile, Thermincola carboxydophila (99%
      similarity). The remainder of clones from the community was most related to T.
      carboxydophila, or uncultured Firmicutes and Deferribacteres. Overall, the data
      indicate that temperate aquatic sediments are a good source of thermophilic
      electrode-reducing bacteria.

PMID- 18080122
TI  - Assessment of the psychological effects of genetic screening for hereditary
      hemochromatosis.
AB  - Discovery of genetic variants of the HFE gene has made it possible to screen for
      hereditary hemochromatosis. However, genetic screening raises ethical, legal,
      social, and psychological questions, which need to be addressed. To assess the
      psychological impact on individuals undergoing genetic screening for hereditary
      hemochromatosis and to determine the effects of providing different levels of
      information to the participants. Male residents, aged 30-50 years (n = 10,993)
      were invited to a genetic screening for hereditary hemochromatosis. Carriers of
      the gene variants H63D, S65C, and C282Y were offered additional biochemical
      screening using serum ferritin and transferrin saturation. Psychological factors
      were evaluated through questionnaires before and after genetic and biochemical
      screening. According to genotype, participants were divided into three groups
      with different risks profiles for having/developing clinical hemochromatosis (at
      risk, uncertain risk, no risk). Before completion of the questionnaires, 929
      participants received only genetic information and 366 received both genetic and
      biochemical information. At-risk participants receiving only genetic information
      generally displayed negative reactions to the test result, whereas participants
      receiving both genetic and biochemical information were more satisfied and had
      fewer negative psychological reactions to the test result. Genetic screening is
      more readily accepted by subjects when genetic information is supported by
      biochemical measurements, especially in participants with a risk of clinical
      disease.

PMID- 18080123
TI  - Celecoxib inhibits production of MMP and NO via down-regulation of NF-kappaB and
      JNK in a PGE2 independent manner in human articular chondrocytes.
AB  - The purpose of this study was to examine the effects of celecoxib on matrix
      metalloproteinases (MMP-1 and MMP-3), nitric oxide (NO), and the phosphorylation
      of nuclear factor-kappaB (NF-kappaB) and three mitogen-activated protein kinases
      (MAPKs), (p38, JNK and ERK) in human articular chondrocytes from normal,
      osteoarthritis, and rheumatoid arthritis cartilages. Celecoxib at 100 nM reduced
      the IL-1beta-induced productions of MMP-1, MMP-3, iNOS, and NO, whereas
      indomethacin at 100 nM showed no effect. The additional stimulation of
      prostaglandin E2 (PGE2) failed to restore those productions, while the production
      of PGE2 were reduced by 1 and 10 microM but not 100 nM of celecoxib. The
      inhibitors of NF-kappaB, JNK and p38, but not ERK, decreased IL-1beta-enhanced
      MMP-1, MMP-3 and NO production, respectively, and 100 nM celecoxib down-regulated
      the phosphorylation of NF-kappaB and JNK but has no effect on either p38 or ERK.
      Celecoxib has inhibitory effects on MMP-1, MMP-3 and NO productions, suggesting
      the protective roles directly on articular chondrocytes. Despite the COX-2
      selectivity, celecoxib affects those productions via not PGE2 but NF-kappaB and
      JNK MAPK.

PMID- 18080124
TI  - Comparison of trimethoprim-sulfamethoxazole and aerosolized pentamidine for
      primary prophylaxis of Pneumocystis jiroveci pneumonia in immunocompromised
      patients with connective tissue disease.
AB  - To evaluate the efficacy of primary prophylaxis for Pneumocystis jiroveci
      pneumonia (PCP) in patients with connective tissue disease (CTD) and
      immunosuppression, we compared trimethoprim-sulfamethoxazole (TMP-SMZ) with
      aerosolized pentamidine. Forty-eight CTD patients of Kitasato University Hospital
      whose CD4+ lymphocyte count in the peripheral blood was less than 300 microl(-1)
      were reviewed from 2002 to 2004. Twenty-seven patients received TMP-SMZ and none
      of them developed PCP. Among 18 patients receiving aerosolized pentamidine, three
      patients developed PCP. These data indicate that TMP-SMZ is better for
      prophylaxis than aerosolized pentamidine.

PMID- 18080125
TI  - Kalanchoe blossfeldiana plants expressing the Arabidopsis etr1-1 allele show
      reduced ethylene sensitivity.
AB  - Transgenic Kalanchoe blossfeldiana Poelln. with reduced ethylene sensitivity in
      flowers was obtained by Agrobacterium tumefaciens-mediated transformation using
      the plasmid pBEO210 containing the mutant ethylene receptor gene etr1-1 from
      Arabidopsis thaliana under the control of the flower-specific fbp1-promoter from
      Petunia. Three ethylene-resistent T0 lines, 300, 324 and 331, were selected and
      analyzed for postharvest-performance and morphological characteristics. Line 324
      was found to be infertile and only slightly less ethylene-sensitive than control
      plants, but lines 300 and 331 had significantly increased ethylene-resistance and
      were fertile. These two lines were analyzed for copy-number of the etr1-1 gene by
      Southern blotting and were crossed with the ethylene-sensitive cultivar 'Celine'
      to create T1 progeny. Line 300 contains two T-DNA copies per nucleus, one of
      which is rearranged, and these are unlinked according to segregation data from
      the crossing to 'Celine' and PCR-analysis of progeny plants. For control plants
      all flowers were closed after 2 days at 2 microl l(-1 )ethylene, but for line 300
      only 33% were closed after 10 days. Line 331 contains three T-DNA copies per
      nucleus and is more sensitive to ethylene than line 300. In the line 300 the etr1
      1 gene was found by RT-PCR to be expressed in petals and stamens but not in
      carpels and sepals. Both lines 300 and 331, and their progeny, appear
      morphologically and physiologically identical to control plants except for the
      higher ethylene resistance. Line 300 and its progeny with only one T-DNA copy
      have very low ethylene sensitivity and may be useful in future breeding.

PMID- 18080126
TI  - Comparative analysis of gene expression between CMS-D8 restored plants and normal
      non-restoring fertile plants in cotton by differential display.
AB  - CMS-D8 and its restorer were developed by introducing the cytoplasm and nuclear
      gene Rf (2) from the wild diploid Gossypium trilobum (D8) into the cultivated
      tetraploid Upland cotton (Gossypium hirsutum). No information is available on how
      the Rf (2) gene interacts with CMS-associated genes and how CMS-D8 cytoplasm
      affects nuclear gene expression. The objective of this study was to identify
      differentially expressed genes in anther tissues between the non-restoring
      fertile maintainer ARK8518 (rf(2) rf(2)) and its isogenic heterozygous D8
      restorer line, ARK8518R (Rf(2) rf(2)) with D8 cytoplasm, by mRNA differential
      display (DD). Out of more than 3,000 DDRT-PCR bands amplified by 31 primer
      combinations from 12 anchor primers and 8 arbitrary decamer primers,
      approximately 100 bands were identified as being qualitatively differentially
      displayed. A total of 38 cDNA fragments including 12 preferentially expressed
      cDNA bands in anther were isolated, cloned and sequenced. Reverse northern blot
      analysis showed that only 4 genes, including genes encoding a Cys-3-His zinc
      finger protein and aminopeptidase, were up-regulated, while 22 genes, including
      genes for phosphoribosylanthranilate transferase (PAT), starch synthase (SS), 4
      coumarate-CoA ligase, electron transporter, calnexin, arginine decarboxylase, and
      polyubiquitin, were down-regulated in the heterozygous restorer ARK8518R. The
      down-regulation of SS explains the lack of starch accumulation in sterile rf(2)
      pollen grains in the heterozygous restored plants. The molecular mechanism of CMS
      and its restoration, specifically the possible roles of SS and PAT genes in
      relation to restoration of Rf(2) to CMS-D8, are discussed. This investigation
      represents the first account of such an analysis in cotton.

PMID- 18080127
TI  - Radiofrequency ablation of high-grade dysplastic nodules in chronic liver
      disease: comparison with well-differentiated hepatocellular carcinoma based on
      long-term results.
AB  - This retrospective study compared the long-term results of percutaneous
      radiofrequency (RF) ablation for high-grade dysplastic nodules (DNs) and well
      differentiated hepatocellular carcinomas (HCCs). Between April 1999 and December
      2006, 20 patients with 21 high-grade DNs (range, 1.2-3.0 cm; mean, 1.9 cm) (group
      1) and 49 with a well-differentiated HCC (range, 1.0-5.0 cm; mean, 2.3 cm) (group
      2) underwent RF ablation. The technique effectiveness, local tumor progression,
      cancer-free and cumulative survivals using the Kaplan-Meier method were compared.
      The technique effectiveness rates at 1 year after RF ablation were 100% (19/19)
      and 94.1% (32/34) in groups 1 and 2, respectively (P > 0.05). The local tumor
      progression rates in groups 1 and 2 were 0% and 20.6% (7/34), respectively (P =
      0.041). The local tumor progression in group 2 was seen on follow-up computed
      tomography 4-58 months (mean, 17 months) after RF ablation. The 1-, 3-, and 5
      year cancer-free survival rates in groups 1 and 2 were 95.0% and 76.9%, 56.2% and
      44.6%, and 38.5% and 24.8%, respectively (P > 0.05). The 1-, 3-, and 5-year
      cumulative survival rates in groups 1 and 2 were 100% and 97.9%, 73.0% and 68.0%,
      and 63.8% and 51.1%, respectively (P > 0.05). Percutaneous RF ablation is
      effective for treating high-grade DNs and well-differentiated HCCs. The long-term
      results after RF ablation of high-grade DNs may be improved compared with those
      of well-differentiated HCCs.

PMID- 18080129
TI  - Basophilic inclusion body disease and neuronal intermediate filament inclusion
      disease: a comparative clinicopathological study.
AB  - While both neuronal intermediate filament inclusion disease (NIFID) and
      basophilic inclusion body disease (BIBD) show frontotemporal lobar degeneration
      and/or motor neuron disease, it remains unclear whether, and how, these diseases
      differ from each other. Here, we compared the clinicopathological characteristics
      of four BIBD and two NIFID cases. Atypical initial symptoms included weakness,
      dysarthria, and memory impairment in BIBD, and dysarthria in NIFID. Dementia
      developed more than 1 year after the onset in some BIBD and NIFID cases. Upper
      and lower motor neuron signs, parkinsonism, and parietal symptoms were noted in
      both diseases, and involuntary movements in BIBD. Pathologically, severe caudate
      atrophy was consistently found in both diseases. Cerebral atrophy was distributed
      in the convexity of the fronto-parietal region in NIFID cases. In both BIBD and
      NIFID, the frontotemporal cortex including the precentral gyrus, caudate nucleus,
      putamen, globus pallidus, thalamus, amygdala, hippocampus including the dentate
      gyrus, substantia nigra, and pyramidal tract were severely affected, whereas
      lower motor neuron degeneration was minimal. While alpha-internexin-positive
      inclusions without cores were found in both NIFID cases, one NIFID case also had
      alpha-internexin- and neurofilament-negative, but p62-positive, cytoplasmic
      spherical inclusions with eosinophilic p62-negative cores. These two types of
      inclusions frequently coexisted in the same neuron. In three BIBD cases,
      inclusions were tau-, alpha-synuclein-, alpha-internexin-, and neurofilament
      negative, but occasionally p62-positive. These findings suggest that: (1) the
      clinical features and distribution of neuronal loss are similar in BIBD and
      NIFID, and (2) an unknown protein besides alpha-internexin and neurofilament may
      play a pivotal pathogenetic role in at least some NIFID cases.

PMID- 18080128
TI  - Rapidly progressive metastatic multicentric epithelioid angiosarcoma of the small
      bowel: a case report and a review of literature.
AB  - BACKGROUND: Angiosarcoma is a rare high-grade neoplasm that frequently involves
      the skin and subcutaneous tissue. Rarely, angiosarcoma can occur in the
      gastrointestinal tract where it frequently exhibits multicentric epithelioid
      morphology. DESIGN: We report a case of multicentric epithelioid angiosarcoma
      (EAS) of the small intestine in a 73-year-old male patient who presented with
      weakness and melena, and was found to have bleeding lesions in the small
      intestine on upper gastrointestinal endoscopy. In addition to this case, we
      extensively reviewed the clinical and pathological features of previously
      reported cases of angiosarcoma of the small intestine in the English literature
      since 1970. RESULTS: Our patient presented with rare and aggressive EAS of the
      small intestine. Despite surgical resection of the lesions, the patient continued
      to worsen and developed rapidly progressive metastatic disease. He died within 4
      months of the diagnosis. CONCLUSIONS: Angiosarcoma, especially of the deep
      tissues and the gastrointestinal tract, is very aggressive and rapidly
      metastatic. The survival rate in these patients is extremely poor, and most
      patients die within 6 months to 1 year of the diagnosis. Treatment usually
      involves surgical resection of the bleeding lesions and frequent blood
      transfusions for symptom alleviation.

PMID- 18080130
TI  - Anti-tumor effect of PDT using Photofrin in a mouse angiosarcoma model.
AB  - Angiosarcoma, a malignant tumor of vascular endothelial cell origin, is a lethal
      disease for which complete cure is rarely seen. The objective of this study was
      to determine the efficiency of photodynamic therapy (PDT) as a new treatment for
      angiosarcoma. PDT (630 nm, 25 J/cm2) using Photofrin for a mouse angiosarcoma
      cell line of human origin (ISOS-1) showed that the rate of cell death increased
      with increase in the concentration of a photosensitizer (LD50: approximately 2
      microg/ml). Furthermore, PDT (630 nm, 100 J/cm2) with Photofrin (5 mg/kg, i.v.)
      in mice transplanted with ISOS-1 cells resulted in complete disappearance of the
      tumor in 40% of mice and marked inhibition of tumor growth in the remaining 60%.
      Significant increases in TUNEL-positive cells and Ki-67-positive cells ware seen
      4 h after PDT, indicating that PDT led to not only cell death but also inhibition
      of the proliferation of angiosarcoma cells. The results show that PDT is
      effective for treatment of angiosarcoma.

PMID- 18080131
TI  - Attractor models of working memory and their modulation by reward.
AB  - This work reports an empirical examination of two key issues in theoretical
      neuroscience: distractibility in the context of working memory (WM) and its
      reward dependence. While these issues have been examined fruitfully in isolation
      (e.g. Macoveanu et al. in Biol Cybern 96(4): 407-19, 2007), we address them here
      in tandem, with a focus on how distractibility and reward interact. In
      particular, we parameterise an observation model that embodies the nonlinear form
      of such interactions, as described in a recent neuronal network model (Gruber et
      al. in J Comput Neurosci 20:153-166, 2006). We observe that memory for a target
      stimulus can be corrupted by distracters in the delay period. Interestingly, in
      contrast to our theoretical predictions, this corruption was only partial.
      Distracters do not simply overwrite target; rather, a compromise is reached
      between target and distracter. Finally, we observed a trend towards a reduced
      distractibility under conditions of high reward. We discuss the implications of
      these findings for theoretical formulations of basal and dopamine (DA)-modulated
      neural bump- attractor networks of working memory.

PMID- 18080133
TI  - Adenohibernoma of the breast.

PMID- 18080132
TI  - Clinical application of aquaporin research: aquaporin-1 in the peritoneal
      membrane.
AB  - Peritoneal dialysis (PD) is an established mode of renal replacement therapy
      based on the exchange of fluid and solutes between blood and a dialysate that has
      been instilled in the peritoneal cavity. The dialysis process involves osmosis,
      as well as diffusive and convective transports through the highly vascularized
      peritoneal membrane. Computer simulations predicted that the membrane contains
      ultrasmall pores responsible for the selective transport of water across the
      capillary endothelium during crystalloid osmosis. The distribution of the water
      channel aquaporin-1 (AQP1), as well as its molecular structure ensuring an
      exquisite selectivity for water, fit with the characteristics of the ultrasmall
      pore. Peritoneal transport studies using AQP1 knockout mice demonstrated that the
      osmotic water flux across the peritoneal membrane is mediated by AQP1. This water
      transport accounts for 50% of the ultrafiltration during PD. Treatment with high
      dose corticosteroids upregulates the expression of AQP1 in peritoneal
      capillaries, resulting in increased water transport and ultrafiltration in rats.
      AQP1 may also play a role during inflammation, as vascular proliferation and
      leukocyte recruitment are both decreased in mice lacking AQP1. These data
      illustrate the potential of the peritoneal membrane as an experimental model in
      the investigation of the role of AQP1 in the endothelium at baseline and during
      inflammation. They emphasize the critical role of AQP1 during PD and suggest that
      manipulating AQP1 expression could be clinically useful in PD patients.

PMID- 18080134
TI  - Developing human minor salivary glands: morphological parallel relation between
      the expression of TGF-beta isoforms and cytoskeletal markers of glandular
      maturation.
AB  - Morphogenesis of salivary glands involves complex coordinated events.
      Synchronisation between cell proliferation, polarisation and differentiation,
      which are dependent on epithelial-mesenchymal interactions and on the
      microenvironment, is a requirement. Growth factors mediate many of these
      orchestrated biological processes and transforming growth factor-beta (TGF-beta)
      appear to be relevant. Using immunohistochemistry and immunofluorescence, we have
      mapped the distribution of TGF-beta 1, 2 and 3 and compared it with the
      expression of maturation markers in human salivary glands obtained from foetuses
      ranging from weeks 4 to 24 of gestation. TGF-beta 1 first appeared during
      canalisation stage in the surrounding mesenchyme and, in the more differentiated
      stages, was expressed in the cytoplasm of acinar cells throughout the adult
      gland. TGF-beta 2 was detected since the bud stage of the salivary gland. Its
      expression was observed in ductal cells and increased along gland
      differentiation, TGF-beta 3 was detected from the canalisation stage of the
      salivary gland, being weakly expressed on ductal cells, and it was the only
      factor detected on myoepithelial cells. The data suggest that TGF-beta have a
      role to play in salivary gland development and differentiation.

PMID- 18080135
TI  - Downregulated parafibromin expression is a promising marker for pathogenesis,
      invasion, metastasis and prognosis of gastric carcinomas.
AB  - Parafibromin is a protein encoded by the hyperparathyroidism 2 oncosuppressor
      gene and its downregulated expression is involved in pathogenesis of parathyroid
      carcinomas. To clarify the roles of parafibromin expression in tumourigenesis and
      progression of gastric carcinomas, it was examined by immunohistochemistry (IHC)
      on tissue microarray containing gastric carcinomas (n = 508), adenomas (n = 45)
      and gastritis (n = 49) with a comparison of its expression with
      clinicopathological parametres of carcinomas. Gastric carcinoma cell lines
      (MKN28, AGS, MKN45, KATO-III and HGC-27) were studied for parafibromin expression
      by IHC and western blot. Parafibromin expression was localised in the nucleus of
      gastric epithelial cells, adenoma, carcinoma cells and cell lines. Its expression
      was gradually decreased from gastritis to gastric carcinoma, through gastric
      adenomas (p < 0.05) and inversely correlated with tumour size, depth of invasion,
      lymphatic invasion, lymph node metastasis and Union Internationale Contre le
      Cancer (UICC) staging (p < 0.05) but not with sex or venous invasion (p > 0.05).
      Parafibromin was strongly expressed in older carcinoma patients compared with
      younger ones (p < 0.05). There was stronger positivity of parafibromin in
      intestinal-type than diffuse-type carcinomas (p < 0.05). Univariate analysis
      indicated cumulative survival rate of patients with positive parafibromin
      expression to be higher than without its expression (p < 0.05). Multivariate
      analysis showed that age, tumour size, depth of invasion, lymphatic invasion,
      lymph node metastasis, UICC staging and Lauren's classification but not sex,
      venous invasion or parafibromin expression were independent prognostic factors
      for carcinomas(p < 0.05). Downregulated parafibromin expression possibly
      contributed to pathogenesis, growth, invasion and metastasis of gastric
      carcinomas. It was considered as a promising marker to indicate the aggressive
      behaviours and prognosis of gastric carcinomas.

PMID- 18080136
TI  - Huge renal cyst with parietal renal cell carcinoma, osseous metaplasia and a
      papillary adenoma: a case report with unique clinicopathological features and
      literature review.
AB  - The unique clinicopathological features of a giant solitary renal cyst with a
      parietal clear cell carcinoma in contiguity with a focus of osseous metaplasia
      and a papillary adenoma are reported. Ultrasonography and computed tomography
      showed a single cyst with a focal wall irregularity. During surgery, a frozen
      section revealed the presence of a renal cell carcinoma of clear cell type, so a
      nephrectomy was performed. After extensive pathological sampling of the cyst's
      wall, a focus of osseous metaplasia in contiguity with the main tumour and a
      microscopic papillary adenoma were found. Diagnostic implications for the present
      case are discussed within a pertinent literature review.

PMID- 18080137
TI  - Primary adrenocortical sarcomatoid carcinoma: case report and review of
      literature.
AB  - Adrenocortical carcinoma (AC) mixed with a sarcoma or sarcoma-like component is
      exceptional, and only six cases have been detailed in the literature, three
      including osteo-, chondro-, or rhabdomyosarcoma components, and three others only
      showing a malignant spindle cell component. These histological subtypes,
      respectively called adrenal carcinosarcomas and sarcomatoid AC, represent poorly
      differentiated and extremely aggressive forms of carcinoma, with locoregional
      recurrence and metastases rapidly arising from the sarcomatous or sarcomatoid
      component, and death occurring in a few months. We report a case of AC in a 31
      year-old man presenting as a nonfunctional tumor, with a histological biphasic
      pattern combining few areas of differentiated AC and extensive areas of
      sarcomatoid spindle cell proliferation. The patient died 3 months of locoregional
      and distant recurrences after surgery despite apparently total tumor resection
      and VP16-cisplatinum chemotherapy. This case underlines the necessity to identify
      and isolate these carcinoma's subtypes with worse prognosis and the difficulties
      to distinguish them from metastatic carcinomas and retroperitoneal sarcomas, in
      relation to the particular adrenal cortex immunoprofile. According to the World
      Health Organization principles of terminology, we suggest these tumors be
      collectively classified as "adrenal sarcomatoid carcinomas," a designation that
      tends to unify all carcinomas with "pleomorphic, sarcomatoid, or sarcomatous
      elements."

PMID- 18080138
TI  - Mucosal colonization of gastric endocrine tumors mimicking mixed neoplasms.
AB  - Two cases of gastric tumors showing mixed composition of endocrine cell clusters
      and exocrine glands and originally diagnosed as mixed neoplasms are described. In
      both cases, the exocrine glandular component was restricted to the upper third of
      the neoplasms being consistently absent in areas of muscular wall invasion and,
      in case 2, in nodal metastases. These glands were in close anatomical contiguity
      with the glands of the overlying gastric mucosa or, in case 1, apparently derived
      from deep pouch-like invaginations of the mucosa. They showed either lack of
      dysplasia (case 1) or mild dysplasia (case 2) with a Ki67 proliferation index
      consistently lower than that of the intramucosal glands. The intratumoral glands
      presented intestinal metaplastic features confirmed by intense Cdx2
      immunostaining that, conversely, was absent in the endocrine component of the
      tumors. The latter showed intense vesicular monoamine transporter 2
      immunoreactivity consistent with its origin from the enterochromaffin-like cells
      of the gastric oxyntic mucosa. On the basis of these findings, it is proposed
      that the exocrine glands do not represent a true neoplastic component of the
      tumors. Although mucosal entrapment by the tumor cannot be ruled out, they more
      likely reflect a hitherto unrecognized mechanism of mucosal colonization of
      gastric endocrine tumors.

PMID- 18080140
TI  - Evaluation of antileishmanial potential of Tinospora sinensis against
      experimental visceral leishmaniasis.
AB  - The chemotherapeutic interventions against visceral leishmaniasis (VL) are
      limited and facing serious concerns of toxicity, high cost, and emerging drug
      resistance. There is a greater interest in new drug developments from
      traditionally used medicinal plants which offers unprecedented diversity in
      structures and bioactivity. With this rationale, ethanolic extract of Tinospora
      sinensis Linn and its four fractions were tested in vitro against promastigotes
      and intracellular amastigotes and in vivo in Leishmania donovani infected
      hamsters. Ethanolic extract exhibited an appreciable activity against
      promastigotes (IC(50) 37.6+/-6.2 microg/ml) and intracellular amastigotes (IC(50)
      29.8+/-3.4 microg/ml). In hamsters, it resulted in 76.2+/-9.2% inhibition at 500
      mg/kg/day x 5 oral dose level. Among fractions, n-butanol imparted highest in
      vitro and in vivo activities. Ethanolic extract and butanol fraction also
      enhances reactive oxygen species (ROS) and nitric oxide (NO) release. The results
      indicate that T. sinensis may provide new lead molecules for the development of
      alternative drugs against VL.

PMID- 18080139
TI  - PEComas: the past, the present and the future.
AB  - The perivascular epithelioid cell (PEC) is a cell type constantly present in a
      group of tumors called PEComas. PEC expresses myogenic and melanocytic markers,
      such as HMB45 and actin. Recently, recurrent chromosomal alterations have been
      demonstrated in PEC. At present, PEComa is a widely accepted entity. In the past
      10 years, the use of this term has allowed to report and describe numerous cases
      permitting to start highlighting the biology of this group of lesions. PEComas
      are related to the genetic alterations of tuberous sclerosis complex (TSC), an
      autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3)
      genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K
      pathway. There are some open questions about PEComas regarding its histogenesis,
      the definition of epithelioid angiomyolipoma and the identification of the
      histological criteria of malignancy. An innovative therapeutic trial using
      rapamycin is under way for tumors occurring in TSC such as renal angiomyolipoma
      and lymphangioleiomyomatosis. Its success could provide the rationale for the use
      of the same drug in other lesions composed of PECs, especially in the malignant
      ones.

PMID- 18080142
TI  - Survival of male Tengmalm's owls increases with cover of old forest in their
      territory.
AB  - The loss and fragmentation of forest habitats have been considered to pose a
      worldwide threat to the viability of forest-dwelling animals, especially to
      species that occupy old forests. We investigated whether the annual survival of
      sedentary male Tengmalm's owls Aegolius funereus was associated with the cover of
      old coniferous forests in Finland. Survival and recapture probabilities varied
      annually with density changes in populations of the main prey (Microtus voles).
      When this variation was controlled for, and relationships between survival and
      proportions of the three different forest age classes (old-growth, middle-aged,
      and young) were modeled separately, the old-growth model was the most
      parsimonious. Survival increased with the cover of old forest, although the
      extent of old forest within owl territories was relatively small (mean
      approximately 12%, range 2-37%). This association, however, varied among years
      and appeared especially in years of increasing vole abundance. At such times, old
      forests may sustain high populations of bank voles Clethrionomys glareolus,
      shrews and small passerines. In addition, old forests may serve as refuges
      against large avian predator species, such as Ural owls Strix uralensis and
      goshawks Accipiter gentilis. Our results suggest that changes in habitat quality
      created by agriculture and forestry may have the potential to reduce adult
      survival, an essential component of fitness and population viability.

PMID- 18080141
TI  - Gac two-component system in Pseudomonas syringae pv. tabaci is required for
      virulence but not for hypersensitive reaction.
AB  - Pseudomonas syringae pv. tabaci 6605 causes wildfire disease on host tobacco
      plants. To investigate the regulatory mechanism of the expression of virulence,
      Gac two-component system-defective mutants, DeltagacA and DeltagacS, and a double
      mutant, DeltagacADeltagacS, were generated. These mutants produced smaller
      amounts of N-acyl homoserine lactones required for quorum sensing, had lost
      swarming motility, and had reduced expression of virulence-related hrp genes and
      the algT gene required for exopolysaccharide production. The ability of the
      mutants to cause disease symptoms in their host tobacco plant was remarkably
      reduced, while they retained the ability to induce hypersensitive reaction (HR)
      in the nonhost plants. These results indicated that the Gac two-component system
      of P. syringae pv. tabaci 6605 is indispensable for virulence on the host plant,
      but not for HR induction in the nonhost plants.

PMID- 18080143
TI  - Utilization of prey from the decomposer system by generalist predators of
      grassland.
AB  - We investigated the linkage between the detrital subsystem and generalist
      predators of meadow ecosystems by manipulating prey availability in two different
      ways: we increased resource availability for the decomposer subsystem and thereby
      decomposer prey by adding mulch materials (detritus enhancement), and we added
      fruitflies (Drosophila melanogaster, Diptera; prey enhancement) to fenced plots.
      Both supplemented materials significantly differed in their (13)C/(12)C and
      (15)N/(14)N ratios from those of the natural litter. We measured density
      responses of detritivorous, herbivorous and predaceous arthropods to the
      increased resource supply. We used ratios of natural stable isotopes of N and C
      in arthropod tissues to trace the flux from the added resources to consumers and
      to relate density responses of consumers to changes in resource supply. Effects
      of resource enhancement propagated through at least two trophic levels, resulting
      in higher densities of major decomposer and predator taxa. Effects of detritus
      enhancement were much stronger than those of prey enhancement. Signatures of
      delta(13)C proved density responses of Collembola taxa to be related to the added
      mulch materials. Among generalist predators, densities of juvenile wolf spiders
      (Lycosidae) responded more to detritus-enhancement than to prey-enhancement
      treatments. In contrast, the density of the web-building linyphiid and the non
      web gnaphosid spiders remained unaffected. Each spider taxon, including those
      which did not respond numerically, was significantly enriched in (13)C in
      detritus-enhancement treatments, suggesting that they gain energy from the
      decomposer system. Numbers of herbivores-cicadellids and aphids-were similar in
      each of the treatments, indicating that they were unaffected by changes in
      predator density. Our results indicate that the lack of a numerical response to
      resource supplementation is not necessarily due to the absence of a trophic
      linkage, but may be caused by compensatory changes in mortality factors such as
      cannibalism and intraguild predation.

PMID- 18080144
TI  - The third World Kidney Day: looking back and thinking forward.

PMID- 18080145
TI  - [Implementation of an electronic patient record. Experience in an
      interdisciplinary pain clinic].
AB  - A complex electronic patient record was implemented in an interdisciplinary pain
      clinic. The goal was to create a tool that would allow structured access to the
      entries made by all specialty groups and permit data analysis for statistical and
      scientific purposes by means of integrated, coded fields. An electronic workflow
      was developed to facilitate the processing of documents. All entries dictated
      were converted to digital form and recorded directly into the electronic chart.
      Additional features included a structured medication list and a connection to the
      hospital's pre-existing electronic records. The various elements to be included
      in the chart were determined by an interdisciplinary team and progressively
      implemented using a commercially available system as a basis. In conclusion,
      implementation of a complex electronic patient record provides a valuable
      instrument for quality control, interdisciplinary collaboration and improved
      efficiency in a large, multimodal pain clinic.

PMID- 18080146
TI  - [Thunderclap headache caused by cerebellar infarction].
AB  - Thunderclap headache is an acute and severe headache and is often the first sign
      of a life-threatening neurovascular disorder. The case of a 44-year-old man is
      described who presented with a thunderclap headache as the only clinical symptom.
      The clinical examination did not reveal any other focal deficits or signs of
      motor or sensory failures. Routine blood tests, cerebral CT as well as
      cerebrospinal fluid analysis showed no pathological results. A cerebral MRI to
      exclude a symptomatic thunderclap headache revealed a right cerebellar
      infarction. This case expands the differential diagnosis of thunderclap headache
      and reinforces the need for magnetic resonance imaging in the evaluation of such
      patients, even when neurological examination, cerebral CT, and cerebrospinal
      fluid analysis are normal.

PMID- 18080147
TI  - Tensile stretching of cervical facet joint capsule and related axonal changes.
AB  - This study examines axonal changes in goat cervical facet joint capsules (FJC)
      subjected to low rate loading. Left C5-C6 FJC was subjected to a series of
      tensile tests from 2 mm to failure using a computer-controlled actuator. The FJC
      strain on the dorsal aspect was monitored by a stereo-imaging system. Stretched
      (n = 10) and unstretched (n = 7) capsules were harvested and serial sections were
      processed by a silver impregnation method. The mean peak actuator displacement
      was 21.3 mm (range: 12-30 mm). The average peak strain encompassing various
      regions of the capsule was 72.9 +/- 7.1%. Complete failure of the capsule was
      observed in 70% of the stretched capsules. Silver impregnation of the sections
      revealed nerve fibers and bundles in all the regions of the capsule. A blinded
      analysis of digital photomicrographs of axons revealed a statistically
      significant number of swollen axons with non-uniform caliber in stretched FJCs.
      Axons with terminal retraction balls, with occasional beaded appearance or with
      vacuolations were also observed. Stretching the FJC beyond physiological range
      could result in altered axonal morphology that may be related to secondary or
      delayed axotomy changes similar to those seen in central nervous system injuries
      where axons are subjected to stretching and shearing. These may contribute to
      neuropathic pain and are potentially related to neck pain after whiplash events.

PMID- 18080148
TI  - Absence of the mutated Trp2 allele but a common polymorphism of the COL9A2
      collagen gene is associated with early recurrence after lumbar discectomy in a
      German population.
AB  - Genetic factors seem to play a role in symptomatic lumbar disc disease (LDD). It
      has been shown previously that a tryptophan mutation of the COL9A2 gene is a
      major risk factor for LDD in a Finish population. The impact of collagen gene
      variations on the relapse rate after lumbar discectomy, however, has not been
      studied so far. Here, we conducted a cross-sectional genotyping study of patients
      who underwent lumbar discectomy to determine the influence of a COL9A2 mutation
      on the recurrence rates. Biopsy samples from 288 patients suffering from LDD with
      and without relapse were analyzed by PCR restriction fragment analysis and direct
      sequencing. The mutated Trp2 allele was not detected in the patients' samples of
      the present study. However, nine patients with recurrent LDD, but only two
      without recurrence were homozygous for the Arg allele. Homozygosity for the Arg
      allele of Col9A2 seems to be more frequent in the patient group with early
      recurrence although the differences in the allele frequencies were statistically
      not significant. In contrast, the Trp2 mutation seems not to be a major
      susceptibility factor for LDD in a German population.

PMID- 18080149
TI  - A novel method for removing the collagen network from acid-etched dentin by
      neodymium:yttrium-aluminum-garnet laser.
AB  - This study proposes a new application for the neodymium:yttrium-aluminum-garnet
      (Nd:YAG) laser in conservative dentistry, which is represented by the removal of
      collagen network from acid-etched dentin. Thirty extracted human upper premolars
      were selected to be given standardized buccal and lingual class V cavities. The
      teeth were randomly divided into three groups, each consisting of ten teeth:
      group 1, acid etch/Nd:YAG laser; group 2, acid etch/10% sodium hypochlorite
      (NaOCl); group 3, acid etch only. Five teeth from each group were prepared for
      the Masson trichrome technique, and the other five teeth were prepared for
      examination by scanning electron microscope. The results showed that the Nd:YAG
      laser can be used successfully as a novel method for removing collagen network
      from acid-etched dentin and can remove the collagen network more thoroughly than
      10% NaOCl.

PMID- 18080150
TI  - Abstracts of the Summer Student Research Award (SSRA) 2007 Research Symposium,
      University College Dublin, Ireland.

PMID- 18080151
TI  - Hospital mortality for Norwood and arterial switch operations as a function of
      institutional volume.
AB  - Regionalization of complex surgical procedures to high-volume centers is a model
      for improving hospital survival. We analyzed the effect of institutional volume
      on hospital mortality for the Norwood and arterial switch operations (ASO) as
      representative high-complexity neonatal cardiac procedures. Analysis of discharge
      data from the 2003 Kids' Inpatient Database (KID) was conducted. Association
      between institutional volume and in-hospital mortality was examined for the ASO
      or Norwood procedure. Logistic regression analysis was performed to calculate the
      probability of hospital mortality for both procedures.Significant inverse
      associations between institutional volume and in-hospital mortality for the
      Norwood procedure (p </= 0.001) and the ASO (p = 0.006) were demonstrated. In
      hospital mortality decreased for the ASO as institutional volume increased, with
      mortality rates of 9.4% for institutions performing two ASOs/year, 3.2% for 10
      ASOs/year, and 0.8% for 20 ASOs/year. Similarly, in-hospital mortality rates for
      hypoplastic left heart syndrome were 34.8% for two Norwood procedures/year, 25.7%
      for 10 Norwood procedures/year, and 16.7% for 20 Norwood procedures/year. An
      inverse relation was observed between in-hospital mortality and institutional
      volume for ASO and the Norwood procedure. These results suggest that selective
      regionalization of complex neonatal cardiac procedures might result in
      significant improvement in hospital survival nationally.

PMID- 18080152
TI  - Medication dosing and renal insufficiency in a pediatric cardiac intensive care
      unit: impact of pharmacist consultation.
AB  - Pediatric patients who have undergone cardiac surgery are at risk for renal
      insufficiency. The impact of pharmacist consultation in the pediatric cardiac
      intensive care unit (ICU) has yet to be defined. Patients admitted to the
      pediatric cardiac ICU at our institution from January through March of 2006 were
      included. Patient information, collected retrospectively, included: demographics,
      cardiac lesion/surgery, height, weight, need for peritoneal or hemodialysis, need
      for mechanical support, highest and lowest serum creatinine, ICU length of stay
      (LOS), renally eliminated medications, pharmacist recommendations (accepted or
      not), and appropriateness of dosing changes.There were 140 total admissions (131
      patients; age: 3.0 +/- 6.3 years) during the study period. In total, 14 classes
      of renally eliminated medications were administered, with 32.6 +/- 56.4 doses
      administered per patient admission. Thirty-seven patient admissions had one or
      more medications adjusted for renal insufficiency; the most commonly adjusted
      medication was ranitidine. Patients who required medication adjustment for renal
      dysfunction were significantly younger compared to those patients not requiring
      medication adjustment. Pharmacist recommendations were responsible for 96% of
      medication adjustments for renal dysfunction, and the recommendations were
      accepted and appropriate all of the time. The monetary impact of pharmacist
      interventions, in doses saved, was approximately $12,000. Pharmacist consultation
      can result in improved dosing of medications and cost savings. The youngest
      patients are most at risk for inappropriate dosing.

PMID- 18080153
TI  - Clinical utility of Doppler echocardiography in assessing aortic stenosis
      severity and predicting need for intervention in children.
AB  - The optimal echocardiographic methodology for predicting need for intervention in
      children with valvar aortic stenosis (VAS) is not known. We reviewed
      echocardiograms and catheterization reports of 79 children (aged 9.5 +/- 5.9
      years) with isolated VAS. The maximum and mean Doppler-predicted gradients from
      the apical (MIGAP), MEGAP)) and the suprasternal or right parasternal (MIGHP),
      MEGHP)) windows were measured. The peak-to-peak catheterization gradient and the
      intervention (if any) were recorded. All sites and methods of Doppler estimation
      of VAS gradient correlated in a linear fashion with the invasive gradient (R2 =
      0.34-0.50) and with one another (R2 = 0.48-0.86). MIGAP and MIGHP overestimated
      the invasive gradient in 60% and 86% of patients, whereas MEGAP and MEGHP
      underestimated the invasive gradient in 94% and 83% of patients, respectively.
      Age and diameter of the ascending aorta had small but significant effects on the
      level of agreement. A MIGHP < or = 55 mm Hg predicted no intervention with 100%
      accuracy, whereas the specificities of a MIGHP > 90 mm Hg, a MEGAP > 50 mm Hg,
      and a (MIGAP + MIGHP)/2 > 70 mm Hg for intervention were 94%, 100%, and 92%,
      respectively. The magnitude of overestimation was significantly lower from the
      apical window. In children with VAS, the best prediction of the catheterization
      gradient could be based on the average of MIGAP and MIGHP.

PMID- 18080154
TI  - Hybrid management for hypoplastic left heart syndrome : an experience from
      Brazil.
AB  - Initial surgical reconstruction for hypoplastic left heart syndrome (HLHS) is
      associated with satisfactory outcomes only in a few referral centers. Moreover,
      there is a persistent high-risk period for sudden death while the patient waits
      for the next surgical procedure. The development of a less invasive approach, so
      called "hybrid," postponing a major surgery outside the neonatal period, might
      reduce the immediate and late surgical burden on these patients. This is a
      retrospective study of a contemporary series of patients with HLHS seen in two
      separate institutions. Patients with HLHS or its variants who underwent a
      "hybrid" management were included in the study. Data are described as the mean
      and standard deviation or absolute numbers and percentage, as appropriate. From
      January 2004 to June 2006, 15 patients (10 male; 5 +/- 3.8 days old and 2.9 +/-
      0.5 kg) were included in the study. Ten had both mitral and aortic atresia; the
      ascending aorta and atrial septal defect measured 2.5 +/- 1.4 and 4.9 +/- 1.2 mm,
      respectively. There were six hospital survivors after stage I (mortality rate
      60%). During the interstage period, all but one patient needed additional
      procedures. One patient died of bacterial meningitis 4 months after stage I. Four
      patients were submitted to stage II operation at 6.6 +/- 0.5 months of age and
      one is waiting for the operation. All four required early reinterventions for
      pulmonary artery stenosis. Only one was discharged home and was not yet submitted
      to the third stage. The hybrid approach for HLHS was associated with poor results
      in this early experience from two independent institutions in a developing
      country. This might have been related to infrastructure and technical problems,
      as well as our own learning curve. Institutions working under the same conditions
      might face similar problems during their initial experience.

PMID- 18080155
TI  - Absence of Chlamydia pneumoniae and signs of atherosclerotic cardiovascular
      disease in adolescents with systemic lupus erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE) have accelerated atherogenesis.
      A recent study suggested that Chlamydia pneumoniae infection might also be a
      contributing factor in the development of atherogenesis in patients with SLE. The
      objective of this study was to investigate the possible association of C.
      pneumoniae infection with markers of atherosclerosis in adolescents with SLE
      compared with age-matched healthy controls. History and exam focused on
      cardiovascular risk factors were obtained from 20 patients with SLE and 20 age-
      and sex-matched controls. Laboratory studies included serum lipid profile and
      high-sensitivity C-reactive protein (hsCRP). Detection of C. pneumoniae in
      peripheral blood mononuclear cells (PBMCs) and in nasopharyngeal swab specimens
      was performed. Carotid Intima-Media Thickness (CIMT) was determined by sonography
      in all subjects. C. pneumoniae DNA was not detected in PBMCs of any of the
      patients or controls. Nasopharyngeal cultures were also negative for C.
      pneumoniae in all patients. CIMT was slightly higher in the SLE group (0.48 +/-
      0.049) compared with controls (0.454 +/- 0.041, p = 0.29). There was no
      significant difference between the two groups in body mass index, blood pressure,
      hsCRP, and serum cholesterol (total, LDL and HDL). Serum triglycerides were
      higher in the lupus group (p = 0.03). Children and adolescents with SLE might
      have accelerated atherosclerosis; however, we did not observe an association with
      C. pneumoniae infection in this population.

PMID- 18080157
TI  - Dressing of the axilla using a water-filled surgical glove after axilla grafting.
AB  - Usually, after grafting of the axilla, it is difficult to obtain a reliable
      dressing using traditional materials including tulls and fluffy gauzes. As an
      alternative to this traditional approach, a sterile surgical glove filled with
      saline can be used to obtain a bulky dressing.

PMID- 18080156
TI  - Novel archaea and bacteria dominate stable microbial communities in North
      America's Largest Hot Spring.
AB  - Boiling Springs Lake is an approximately 12,000 m(2), 55 degrees C, pH 2 thermal
      feature located in Lassen Volcanic National Park in northern California, USA. We
      assessed the microbial diversity in the lake by analyzing approximately 500
      sequences from clone libraries constructed using three different primer sets
      targeted at 16S rRNA genes and one targeted at 18S rRNA genes. We assessed the
      stability of the microbial community by constructing terminal restriction
      fragment length polymorphism (T-RFLP) profiles using DNA extracts collected in
      four separate years over a 7-year period. The four most prevalent phylotypes in
      the clone libraries shared an average approximately 85% sequence identity with
      their closest cultured relatives, and three fourths of the prokaryotic sequences
      shared less than 91% identity. Phylogenetic analyses revealed novel lineages
      devoid of cultivated representatives in the Bacterial and Archaeal domains. Many
      detected phylotypes were related to taxonomically diverse genera previously
      associated with high-temperature environments, while others were related to
      diverse Proteobacteria and Firmicutes that would not be expected to grow within
      BSL conditions. All of the 18S rRNA sequences most closely matched fungi in the
      phyla Ascomycota and Basidiomycota (91-99% identity). T-RFLP detected fragments
      corresponding to the most prevalent phylotypes detected in 16S rRNA gene
      libraries. The T-RFLPs from separate years were similar, and the water-derived T
      RFLPs were similar to the sediment-derived (average pairwise Sorenson's
      similarity index of 0.74, and 0.78, respectively). Collectively, these results
      indicate that a stable community of diverse novel microorganisms exists in
      Boiling Springs Lake.

PMID- 18080159
TI  - Infections after plastic procedures: incidences, etiologies, risk factors, and
      antibiotic prophylaxis.
AB  - BACKGROUND: Through a review of the English literature, this study aimed to
      assess the incidence, etiology, risk factors, and preventive measures for
      postoperative infections occurring after plastic surgery operations. METHODS: All
      studies describing the occurrence of infections after plastic surgery procedures
      including case reports, prospective trials, and retrospective series were
      selected. RESULTS: The 85 articles analyzed showed that incidences differ greatly
      among procedures and seem to be influenced by different and specific risk factors
      for each operation. Etiologic agents are primarily bacteria, although
      mycobacteria, virus, and fungi also have been described. No agreement exists on
      the use of antibiotic prophylaxis, except for abdominoplasties, because few
      specific prospective trials are present in the literature. CONCLUSIONS:
      Infections remain an important problem in plastic surgery with different points
      that still need to be clarified. Hopefully, in the future prospective randomized
      trials will definitively address this issue in order to provide plastic surgeons
      with clear and unbiased guidelines on its prevention and management.

PMID- 18080161
TI  - Predictors of outcome after abdominal aortic aneurysm rupture.

PMID- 18080162
TI  - Distribution and function of the nacrein-related proteins inferred from
      structural analysis.
AB  - Nacrein is the first identified molluscan organic matrix (OM) component
      considered to be specifically involved in nacreous layer formation (Miyamoto et
      al. in Proc Natl Acad Sci USA 93:9657-9660, 1996); however, its localization in
      shell microstructures and phylogeny of molluscs and function still remain
      unclear. Therefore, to elucidate the functions of the nacrein-related proteins,
      we set up three experiments focused on (1) the primary structure of the nacrein
      related proteins, (2) the tertiary structure of nacrein, and (3) in vitro
      crystallization of the proteins. In regard to the first experiment, our Western
      blot analysis and cDNA cloning clearly indicated for the first time the common
      occurrence of nacrein-related proteins both biochemically and genetically,
      independent of molluscan phylogeny and shell microstructures. Together with the
      data reported so far, we classified nacrein-related proteins into four types.
      Second, we determined the overall structure of nacrein via small-angle x-ray
      scattering via the program DAMMIN. This kind of research has never yet been
      attempted for the molluscan OM proteins. Our results inferred the structure of
      nacrein to be N-shaped based on the low-resolution solution dummy atom model
      structures that could be derived from the presence of the NG-repeat domain that
      was intercalated into two CA domains. Third, the result of the crystallization
      experiment revealed inhibitory activity of crystal formation for nacrein-related
      proteins when present in free state but the same molecule, when attached to the
      ISM, may regulate the form and size of aragonite crystal. These results
      demonstrate the fundamentally important function of nacrein-related proteins in
      molluscan shell formation.

PMID- 18080163
TI  - Ethyl 4-methyl heptanoate: a male-produced pheromone of Nicrophorus vespilloides.
AB  - Sexually mature male beetles of the genus Nicrophorus (Coleoptera: Silphidae)
      exhibit a conspicuous behavior, recognized as pheromone-releasing activity.
      Laboratory and field studies demonstrated that females are attracted to males
      that exhibit this behavior, both on or off reproductive resources. Here, we
      report the results of a study in which volatile chemicals released by calling
      Nicrophorus vespilloides were collected by solid-phase microextraction and
      analyzed by using coupled gas chromatography-mass spectrometry. These analyses
      revealed that ethyl 4-methyl heptanoate and (E)-geranylacetone are emitted by
      males that engage in the behavior. In the field, traps baited with racemic ethyl
      4-methyl heptanoate caught roughly equal numbers of male and female N.
      vespilloides. Some male and female Nicrophorus vespillo and male Nicrophorus
      humator were also caught in traps baited with this compound. Traps baited with
      (E)-geranylacetone did not catch significant numbers of beetles.

PMID- 18080164
TI  - Solid-phase microextraction method for in vivo measurement of allelochemical
      uptake.
AB  - Solid-phase microextraction (SPME) was used to measure allelochemical uptake by
      tomato plants in vivo. Exogenously applied 1,8-cineole was rapidly taken up by
      tomato, with the first traces of cineole being detected in the tomato stem just 1
      2 h after a single application of 0.5 mM cineole to soil. The pulse of cineole
      persisted in the tomato stem for 72 h. When cineole concentrations were measured
      24 h after a single application, trace amounts of cineole could be detected in
      tomato stem fluid at application concentrations as low as 50 microM. Tomato was
      also found to take up camphor, menthol, and coumarin, but not carveol. In
      preliminary tests with common ragweed (Artemisia annuifolia L.) and purslane
      (Portulaca oleraceae L.) plants growing in garden beds, both ragweed and purslane
      took up 1,8-cineole, and purslane also took up camphor. The quantitation of
      allelochemical uptake by plants is considered to be a crucial test of hypotheses
      of allelopathic effects, but demonstration of allelochemical uptake has had to be
      inferred based on observed toxicity due to the lack of methods to measure uptake
      in vivo. This new technique now provides a means of tracking compounds within
      target plants. Furthermore, the demonstrated rapid uptake of 1,8-cineole by
      plants suggests a potential mechanism whereby brief pulses of allelochemicals
      over an extended period of time might be able to exert an allelopathic effect on
      plants.

PMID- 18080165
TI  - An antiaphrodisiac in Heliconius melpomene butterflies.
AB  - Gilbert (1976) suggested that male-contributed odors of mated females of
      Heliconius erato could enforce monogamy. We investigated the pheromone system of
      a relative, Heliconius melpomene, using chemical analysis, behavioral
      experiments, and feeding experiments with labeled biosynthetic pheromone
      precursors. The abdominal scent glands of males contained a complex odor bouquet,
      consisting of the volatile compound (E)-beta-ocimene together with some trace
      components and a less volatile matrix made up predominately of esters of common
      C16- and C18-fatty acids with the alcohols ethanol, 2-propanol, 1-butanol,
      isobutanol, 1-hexanol, and (Z)-3-hexenol. This bouquet is formed during the first
      days after eclosion, and transferred during copulation to the females. Virgin
      female scent glands do not contain these compounds. The transfer of ocimene and
      the esters was shown by analysis of butterflies of both sexes before and after
      copulation. Additional proof was obtained by males fed with labeled D-13C6-
      glucose. They produced 13C-labeled ocimene and transferred it to females during
      copulation. Behavioral tests with ocimene applied to unmated females showed its
      repellency to males. The esters did not show such activity, but they moderated
      the evaporation rate of ocimene. Our investigation showed that beta-ocimene is an
      antiaphrodisiac pheromone of H. melpomene.

PMID- 18080166
TI  - Aggressive surgical management of peritoneal carcinomatosis with low mortality in
      a high-volume tertiary cancer center.
AB  - BACKGROUND: Cytoreductive surgery (CS) combined with hyperthermic intraperitoneal
      chemotherapy (HIPEC) for treatment of peritoneal carcinomatosis (PC)
      traditionally involves high perioperative morbidity and mortality. We report our
      experience performing CS-HIPEC in a high-volume regional perfusion program
      designed to limit morbidity and mortality. METHODS: A total of 122 patients
      underwent 124 CS-HIPEC procedures. Common tumors treated with CS-HIPEC included
      appendiceal (38.5%), colorectal (24.6%), and ovarian cancers (13.1%), and
      peritoneal mesothelioma (12.3%). Complete cytoreduction was performed in all
      patients, with organ resections performed as necessary. RESULTS: R0 resection was
      achieved in 28.7% of cases, R1 in 54.9%, and R2 in 16.4%. Median operative time
      was 460 minutes (range, 250-840 minutes), and median blood loss was 1150 mL
      (range, 10-14,000 mL). Median hospital and intensive care unit stays were 12 days
      (range, 6-50 days) and 3 days (range, 0-41 days), respectively. Grade 3 or 4
      morbidity by National Cancer Institute criteria (major morbidity) was seen in
      29.8% of cases, with overall morbidity 56.5%. Independent prognostic variables
      for major morbidity included number of anastomoses and degree of cytoreduction.
      In-hospital and 30-day mortality rates were 0% and 1.6%, respectively. The most
      favorable diagnosis was appendiceal cancer, for which 2-year survival was 66.7%,
      with lower-grade histologic subtypes of appendiceal cancer reaching 85.7% 2-year
      survival. Colorectal cancer had 2-year survival of 36.7%. CONCLUSIONS: In a high
      volume center with extensive experience treating peritoneal malignancies,
      perioperative mortality can be lowered to nearly zero, although morbidity remains
      high. CS-HIPEC procedures should be studied further in a controlled manner to
      help define their important role in the care of patients with PC.

PMID- 18080167
TI  - Hyperammonemic encephalopathy caused by carnitine deficiency.
AB  - Carnitine is an essential co-factor in fatty acid metabolism. Carnitine
      deficiency can impair fatty acid oxidation, rarely leading to hyperammonemia and
      encephalopathy. We present the case of a 35-year-old woman who developed acute
      mental status changes, asterixis, and diffuse muscle weakness. Her ammonia level
      was elevated at 276 microg/dL. Traditional ammonia-reducing therapies were
      initiated, but proved ineffective. Pharmacologic, microbial, and autoimmune
      causes for the hyperammonemia were excluded. The patient was severely
      malnourished and her carnitine level was found to be extremely low. After
      carnitine supplementation, ammonia levels normalized and the patient's mental
      status returned to baseline. In the setting of refractory hyperammonemia, this
      case illustrates how careful investigation may reveal a treatable condition.

PMID- 18080168
TI  - A daughter's duty.

PMID- 18080169
TI  - Laparoscopic approach to colorectal procedures in the obese patient: risk factor
      or benefit?
AB  - BACKGROUND: Obesity is a modern-day phenomenon that is increasing throughout the
      world. The aim of the present study was to provide data to establish whether the
      laparoscopic approach to colorectal surgery in the obese patient represents a
      risk or, rather, a benefit for the patient. METHOD: The data presented in this
      paper were obtained within the framework of a prospective multicenter study
      initiated by the "Laparoscopic Colorectal Surgery Study Group (LCSSG)" and
      performed on 5,853 recruited patients. The perioperative course was compared
      between the three groups: nonobese, obesity grade I, and obesity grade II/III.
      RESULTS: Increasing body mass index correlated with a highly significant increase
      in the duration of the operation (nonobese 167 min, grade I 182 min, grade II/III
      191 min; p < 0.001) and in the conversion rate (nonobese 5.5%, obesity grade I
      7.9%, obesity grade II/III 13.1%; p < 0.001). The intraoperative complication
      rate also showed a tendency to increase (nonobese 5.0%, grade I 6.2%, grade
      II/III 7.1%; p = 0.219). In contrast, no significant differences were found
      between the groups with regard to the postoperative complication rate (nonobese
      20.7%, grade I 21.0%, grade II/III 20.2%), the reoperation rate (nonobese 4.1%,
      grade I 3.9%, grade II/III 3.6%), and the postoperative mortality rate (nonobese
      1.1%, grade I 1.9%, grade II/III 1.8%). CONCLUSION: Laparoscopic colorectal
      surgery is clearly more technically demanding in the obese patient. Apart from
      this, however, it is not associated with any increased risk of postoperative
      complications, and thus demonstrates that the pathologically overweight patient
      can benefit to a particular degree from the laparoscopic modality.

PMID- 18080170
TI  - Involuntary vs. voluntary hospital admission. A systematic literature review on
      outcome diversity.
AB  - This article systematically reviews the literature on the outcome of acute
      hospitalization for adult general psychiatric patients admitted involuntarily as
      compared to patients admitted voluntarily. Inclusion and exclusion criteria
      qualified 41 out of 3,227 references found in Medline and PSYNDEXplus literature
      searches for this review. The authors independently rated these articles on six
      pre-defined indicators of research quality, carried out statistical comparisons
      ex-post facto where not reported, and computed for each adequate result the
      effect size index d for the comparison of means, and the Phi- or contingency
      coefficient for cross-tabulated data. Methodological quality of the studies,
      coming mostly from North American and European countries, showed significant
      variation and was higher concerning service-related than clinical or subjective
      outcomes. Main deficits appeared in sample size estimation, lack of clear follow
      up time-points, and the absence of standardized instruments used to assess
      clinical outcomes. Length of stay, readmission risk, and risk of involuntary
      readmission were at least equal or greater for involuntary patients. Involuntary
      patients showed no increased mortality, but did have higher suicide rates than
      voluntary patients. Further, involuntary patients demonstrated lower levels of
      social functioning, and equal levels of general psychopathology and treatment
      compliance; they were more dissatisfied with treatment and more frequently felt
      that hospitalization was not justified. Future methodologically-sound studies
      exploring this topic should focus on patient populations not represented here.
      Further research should also clarify if the legal admission status is
      sufficiently valid for differentiating the outcome of acute hospitalization.

PMID- 18080171
TI  - Risperidone versus haloperidol in children and adolescents with AD : a
      randomized, controlled, double-blind trial.
AB  - OBJECTIVE: The aim of the study was to compare safety, efficacy and tolerability
      of risperidone with haloperidol in the treatment of Autistic Disorder (AD).
      METHOD: This study was designed as a double-blind, prospective, for a 12-week
      period. A total of 30 subjects, between the ages of 8 and 18 with AD based on DSM
      IV criteria, were included in the study. Behavioral Rating Scales were performed
      by the investigators and the parents. Safety assessment included vital signs,
      electrocardiogram, electroencephalogram, adverse events, laboratory tests,
      extrapyramidal symptoms and the side effects. Both treatments were applied in a
      once daily dosage regimen of 0.01-0.08 mg/kg/day. RESULTS: The reduction from
      baseline in Ritvo-Freeman Real Life Rating Scale (RF-RLRS), sensory motor
      (subscale I) and language (subscale V) scores were significant in risperidone
      group (P < 0.05). Compared to haloperidol, risperidone led to a significantly
      greater reduction in the Aberrant Behavior Checklist (ABC) and Turgay DSM-IV
      Pervasive Developmental Disorder (PDD) scale scores (P < 0.05 and P < 0.01).
      There was a greater increase of prolactin in the risperidone group, while alanine
      amino transferase (ALT) had further increased in the haloperidol group. Sensory
      motor behaviors (subscale I) and language at the end of the 12th week, RF-RLRS
      sensory motor and language subscale scores decreased in the risperidone group
      further than the other group (P < 0.05). CONCLUSIONS: Risperidone was found to be
      more effective than haloperidol in the treatment of behavioral symptoms,
      impulsivity, language skills, and impaired social relations in children with AD.
      These results demonstrated that both drugs were safe and well tolerated in the
      treatment of AD.

PMID- 18080172
TI  - A personal tribute to Joseph R. Robinson: an inspiration for all generations.

PMID- 18080173
TI  - HNF4alpha is a crucial modulator of the cholesterol-dependent regulation of
      NPC1L1.
AB  - PURPOSE: Niemann-Pick C1-like 1 (NPC1L1) has been identified as a target of
      ezetimibe and found to be responsible for intestinal cholesterol absorption.
      Although, it was recently demonstrated that sterol responsive element binding
      protein 2 (SREBP2) is responsible for the cholesterol-dependent down-regulation
      of NPC1L1, the molecular mechanism of NPC1L1 expression is not fully understood.
      In the present study, we examined the involvement of hepatocyte nuclear factor
      4alpha (HNF4alpha), a key modulator of lipid metabolism, in the transcriptional
      regulation of human NPC1L1 gene. METHODS: Reporter gene assays and EMSAs were
      performed using human NPC1L1 promoter constructs and the effect of siHNF4alpha
      was examined. RESULTS: Transfection of SREBP2 induced the transcriptional
      activities of NPC1L1 and additional transfection of HNF4alpha results in a marked
      stimulation of the activities. Studies with deletion mutants indicated that
      important elements are located within 264 nt upstream in the human NPC1L1
      promoter. In addition, studies with mutations in putative binding sites of
      HNF4alpha indicated the existence of binding sites in -209 to -197 and -52 to 
      40. Moreover, HNF4alpha knockdown resulted in the reduced expression and
      regulation by cholesterol. CONCLUSIONS: It is concluded that HNF4alpha plays a
      crucial role in the expression and regulation of human NPC1L1 gene.

PMID- 18080175
TI  - Building an understanding of cystic fibrosis on the foundation of ABC transporter
      structures.
AB  - Cystic fibrosis (CF) is a fatal disease affecting the lungs and digestive system
      by impairment of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
      While over 1000 mutations in CFTR have been associated with CF, the majority of
      cases are linked to the deletion of phenylalanine 508 (delta F508). F508 is
      located in the first nucleotide binding domain (NBD1) of CFTR. This mutation is
      sufficient to impair the trafficking of CFTR to the plasma membrane and, thus,
      its function. As an ABC transporter, recent structural data from the family
      provide a framework on which to consider the effect of the delta F508 mutation on
      CFTR. There are fifty-seven known structures of ABC transporters and domains
      thereof. Only six of these structures are of the intact transporters. In
      addition, modern bioinformatic tools provide a wealth of sequence and structural
      information on the family. We will review the structural information from the
      RCSB structure repository and sequence databases of the ABC transporters. The
      available structural information was used to construct a model for CFTR based on
      the ABC transporter homologue, Sav1866, and provide a context for understanding
      the molecular pathology of Cystic Fibrosis.

PMID- 18080174
TI  - Mink growth hormone structural-functional relationships: effects of renaturing
      and storage conditions.
AB  - Fourier-transform infrared spectroscopy, in vitro bioassay and enzyme-linked
      immunoassay were used to study the structural-functional relationships of
      recombinant mink growth hormone (mGH), refolded and stored under different
      conditions. Porcine GH (pGH) was synthesized and used as an example. These two
      hormones, when refolded and stored the same way, had the same secondary
      structures, biological and immunological efficacy, and biological potency. Only
      the immunological potency differed, mGH being significantly less potent than pGH.
      Renaturation pH and storing frozen or at 4 degrees C in 5% glycerol did not
      affect either the secondary structure or the activity. However, freeze-drying
      raised the content of buried alpha-helices and lowered that of solvated alpha
      helices and of unordered structures. These conformational changes were associated
      with a reduction of immunological and biological potency of mGH and of
      immunological potency of pGH. These findings provide original information on the
      secondary structure of mGH, and show that conformational changes induced by
      lyophilization adversely affect its activity.

PMID- 18080176
TI  - Utility of the Revised Level of Service Inventory (LSI-R) in predicting
      recidivism after long-term incarceration.
AB  - Assessing an inmate's risk for recidivism may become more challenging as the
      length of incarceration increases. Although the population of Long-Term Inmates
      (LTIs) is burgeoning, no risk assessment tools have been specifically validated
      for this group. Based on a sample of 1,144 inmates released in a state without
      parole, we examine the utility of the Level of Service Inventory-Revised (LSI-R)
      in assessing risk of general and violent felony recidivism for LTIs (n = 555).
      Results indicate that (a) the LSI-R moderately predicts general, but not
      necessarily violent, recidivism, and (b) this predictive utility is not moderated
      by LTI status, and is based in part on ostensibly dynamic risk factors.
      Implications for informing parole decision-making and risk management for LTIs
      are discussed.

PMID- 18080177
TI  - Atrial fibrillation surgery in nonrheumatic mitral valve disease.
AB  - Atrial fibrillation (AF) is present in 30-50% of patients presenting for mitral
      valve surgery. If left untreated, AF in these patients is associated with
      increased morbidity and, possibly, increased mortality. Therefore, concomitant
      management of the arrhythmia is indicated in most mitral valve patients with
      preexisting AF. The cut-and-sew Cox-Maze III procedure is extremely effective,
      eliminating AF in 80-95%; however, it has been supplanted by newer operations
      that rely upon alternate energy sources to create lines of conduction block.
      Early and midterm results are good with a variety of technologies. Choice of
      lesion set remains a matter of debate, but success of ablation appears to be
      enhanced by a biatrial lesion set and exceeds 90% in some series. Targeted areas
      for improvement in combined mitral valve surgery and AF ablation include
      acceptance of uniform standards for reporting results, development of improved
      technology for ablation and intraoperative assessment, and creation of
      instrumentation that facilitates minimally invasive approaches.

PMID- 18080178
TI  - Intergenerational relations in a context of industrial transition: a study of
      agricultural labor from migrants in Nang Rong, Thailand.
AB  - This work investigates intergenerational relations in a rural setting
      experiencing the transition from rural subsistence to urban industrial economy.
      Help with harvesting rice from migrant children to their aging parents is used to
      illustrate changes that occur. The setting is Nang Rong, Thailand, an
      agricultural region that has experienced social, economic, and demographic
      transformations in the last three decades. In Nang Rong, out-migrants are young
      adults. Their parents, who remain in rural villages, are approaching ages where
      it becomes difficult to do agricultural labor. The migration of young adults
      contributes to a loss of household labor which puts pressure on households to
      meet their basic subsistence needs. Rice harvest help from returning or visiting
      migrants impacts intergenerational relations between adult children and parents.
      Results show that migrants are more likely to help with the rice harvest if their
      origin household owns securely titled land, and if the migrant has lower human
      capital achievements. Parents may use land as a strategic bequest to elicit
      support, which is consistent with an intergenerational bargaining perspective.

PMID- 18080180
TI  - Measures of spatial similarity and response magnitude in MEG and scalp EEG.
AB  - Sensor selection is typically used in magnetoencephalography (MEG) and scalp
      electroencephalography (EEG) studies, but this practice cannot differentiate
      between changes in the distribution of neural sources versus changes in the
      magnitude of neural sources. This problem is further complicated by (1) subject
      averaging despite sizable individual anatomical differences and (2) experimental
      designs that produce overlapping waveforms due to short latencies between
      stimuli. Using data from the entire spatial array of sensors, we present simple
      multivariate measures that (1) normalize against individual differences by
      comparison with each individual's standard response; (2) compare the similarity
      of spatial patterns in different conditions (angle test) to ascertain whether the
      distribution of neural sources is different; and (3) compare the response
      magnitude between conditions which are sufficiently similar (projection test).
      These claims are supported by applying the reported techniques to a short-term
      word priming paradigm as measured with MEG, revealing more reliable results as
      compared to traditional sensor selection methodology. Although precise cortical
      localization remains intractable, these techniques are easy to calculate,
      relatively assumption free, and yield the important psychological measures of
      similarity and response magnitude.

PMID- 18080179
TI  - An experimentally constrained computational model of NMDA oscillations in lamprey
      CPG neurons.
AB  - Rhythmicity is a characteristic of neural networks responsible for locomotion. In
      many organisms, activation of N-methyl-D: -aspartate (NMDA) receptors leads to
      generation of rhythmic locomotor patterns. In addition, single neurons can
      display intrinsic, NMDA-dependent membrane potential oscillations when
      pharmacologically isolated from each other by tetrodotoxin (TTX) application.
      Such NMDA-TTX oscillations have been characterized, for instance, in lamprey
      locomotor network neurons. Conceptual and computational models have been put
      forward to explain the appearance and characteristics of these oscillations.
      Here, we seek to refine the understanding of NMDA-TTX oscillations by combining
      new experimental evidence with computational modelling. We find that, in contrast
      to previous computational predictions, the oscillation frequency tends to
      increase when the NMDA concentration is increased. We develop a new, minimal
      computational model which can incorporate this new information. This model is
      further constrained by another new piece of experimental evidence: that regular
      looking NMDA-TTX oscillations can be obtained even after voltage-dependent
      potassium and high-voltage-activated calcium channels have been pharmacologically
      blocked. Our model conforms to several experimentally derived criteria that we
      have set up and is robust to parameter changes, as evaluated through sensitivity
      analysis. We use the model to re-analyze an old NMDA-TTX oscillation model, and
      suggest an explanation of why it failed to reproduce the new experimental data
      that we present here.

PMID- 18080182
TI  - Surface alpha 2-3- and alpha 2-6-sialylation of human monocytes and derived
      dendritic cells and its influence on endocytosis.
AB  - Several glycoconjugates are involved in the immune response. Sialic acid is
      frequently the glycan terminal sugar and it may modulate immune interactions.
      Dendritic cells (DCs) are antigen-presenting cells with high endocytic capacity
      and a central role in immune regulation. On this basis, DCs derived from
      monocytes (mo-DC) are utilised in immunotherapy, though many features are ignored
      and their use is still limited. We analyzed the surface sialylated glycans
      expressed during human mo-DC generation. This was monitored by lectin binding and
      analysis of sialyltransferases (ST) at the mRNA level and by specific enzymatic
      assays. We showed that alpha 2-3-sialylated O-glycans and alpha 2-6- and alpha 2
      3-sialylated N-glycans are present in monocytes and their expression increases
      during mo-DC differentiation. Three main ST genes are committed with this
      rearrangement: ST6Gal1 is specifically involved in the augmented alpha 2-6
      sialylated N-glycans; ST3Gal1 contributes for the alpha2-3-sialylation of O
      glycans, particularly T antigens; and ST3Gal4 may contribute for the increased
      alpha2-3-sialylated N-glycans. Upon mo-DC maturation, ST6Gal1 and ST3Gal4 are
      downregulated and ST3Gal1 is altered in a stimulus-dependent manner. We also
      observed that removing surface sialic acid of immature mo-DC by neuraminidase
      significantly decreased its endocytic capacity, while it increased in monocytes.
      Our results indicate the STs expression modulates the increased expression of
      surface sialylated structures during mo-DC generation, which is probably related
      with changes in cell mechanisms. The ST downregulation after mo-DC maturation
      probably results in a decreased sialylation or sialylated glycoconjugates
      involved in the endocytosis, contributing to the downregulation of one or more
      antigen-uptake mechanisms specific of mo-DC.

PMID- 18080181
TI  - Maternal modeling and the acquisition of fear and avoidance in toddlers:
      influence of stimulus preparedness and child temperament.
AB  - The aim of the present study was to investigate the influence of maternal
      modeling on the acquisition of fear and avoidance towards fear-relevant and fear
      irrelevant, novel stimuli in a sample of 71 toddlers. Children were shown a
      rubber snake or spider (fear-relevant objects) and a rubber mushroom or flower
      (fear-irrelevant objects), which were alternately paired with either negative or
      positive expression by their mothers. Both stimuli were presented again after a 1
      and a 10-min delay, while mothers maintained a neutral expression. The toddlers
      showed increased fear and avoidance of the objects following negative reaction
      from their mothers than following positive maternal expression. This was
      similarly true for both fear-relevant and fear-irrelevant stimuli. In addition,
      no association was found between child temperament and behavioral responses and a
      weak association emerged between child temperament and emotional responses. The
      results demonstrate that young children can rapidly form conditioned emotional
      and behavioral responses via maternal reactions regardless of stimulus
      preparedness or child temperament. It is suggested that early maternal modeling
      may be relevant to a broad spectrum of fearful reactions.

PMID- 18080183
TI  - The structural plasticity of heparan sulfate NA-domains and hence their role in
      mediating multivalent interactions is confirmed by high-accuracy (15)N-NMR
      relaxation studies.
AB  - Considering the biological importance of heparan sulfate (HS) and the significant
      activity of its highly-sulfated regions (S-domains), the paucity of known
      functions for the non-sulfated NA-domains is somewhat puzzling. It has been
      suggested that chain dynamics within the NA-domains are the key to their
      functional role in HS. In this study, we investigate this hypothesis using state
      of-the-art nuclear magnetic resonance (NMR) experiments at multiple frequencies.
      To resolve the problem of severe overlap in (1)H-NMR spectra of repetitive
      polysaccharides from proteoglycans, we have prepared oligosaccharides with the
      chemical structure of HS NA-domains containing the (15)N nucleus, which has
      enough chemical shift dispersion to probe the central residues of octasaccharides
      at atomic resolution using 600 MHz NMR. By performing NMR relaxation experiments
      at three magnetic-field strengths, high quality data on internal dynamics and
      rotational diffusion was obtained. Furthermore, translational diffusion could
      also be measured by NMR using pulse field gradients. These experimental data were
      used, in concert with molecular dynamics simulations, to provide information on
      local molecular shape, greatly aiding our relaxation analyses. Our results, which
      are more accurate than those presented previously, confirm the higher flexibility
      of the NA-domains as compared with reported data on S-domains. It is proposed
      that this flexibility has two functional roles. First, it confers a greater area
      of interaction from the anchoring point on the core protein for the bioactive S
      domains. Secondly, it allows multiple interactions along the same HS chain that
      are dynamically independent of each other.

PMID- 18080184
TI  - Intervention for apoptosis in cardiomyopathy.
AB  - Apoptosis plays an important role in pathogenesis of primary and secondary
      cardiomyopathies. It is proposed that antiapoptotic interventions may constitute
      an effective strategy for these diseases. Some of the antiapoptotic interventions
      are "old wine in a new bottle" measures already included in the conventional
      pharmacotherapy. As specific antiapoptotic treatment, caspase inhibitors and anti
      TNF-alpha antibody are in early phases of clinical trials in non-cardiac diseases
      or being contemplated for clinical studies. Non-pharmacotherapies such as cardiac
      resynchronization and left ventricular assist device also exert cardioprotection
      partly by antiapoptotic mechanisms. In the field of regenerative medicine,
      myocardial transplantation of bone marrow-derived stem cells has been performed.
      Although it is controversial whether it is a true regenerative medicine or the
      cytokine therapy, antiapoptotic effect of transplanted cells may also have a role
      in cardioprotection. Moreover, apoptosis may develop despite efforts for
      cardioprotection in some severe situations of heart failure. Cardiac repair and
      regeneration by cardiac stem cells may compensate a loss of cardiomyocytes
      avoiding a deleterious situation. Therefore, protection and/or potentiation of
      such effects by cardiac stem cells appear to be promising therapeutic strategy in
      the future. In this review, we discuss about the antiapoptotic interventions for
      cardiomyopathies in the "real world" and the future of clinical cardiology.

PMID- 18080185
TI  - Effects of nickel and temperature on the ground beetle Pterostichus
      oblongopunctatus (Coleoptera: Carabidae).
AB  - In natural ecosystems it is not unusual for an organism to be exposed both to
      chemical and physical stressful factors at the same time. Herein we present
      results of the study on nickel toxicity to the carabid beetle, Pterostichus
      oblongopunctatus, and effect of Ni and temperature on the beetles respiration
      rates. In the first part of the study (Experiment I) we measured the survival,
      respiration rates and internal Ni concentrations in animals exposed for 245 d at
      constant temperature (20 degrees C) to food contaminated with Ni at nominal
      concentrations 0; 600; 1,200; 2,400; 4,800; and 9,600 mg kg(-1) dry weigh (dw).
      The LC(50) was estimated at 8,351 mg Ni kg(-1), with no effect on fertility. We
      found a significant positive correlation between Ni concentration in food and
      internal body concentration of Ni, and a negative correlation between Ni exposure
      and the respiration rate. Based on these results, the concentration of 2,400 mg
      kg(-1) (LOEC for the respiration rate) was selected for the second part of the
      study (Experiment II) in which field-collected males of P. oblongopunctatus were
      exposed to Ni-contaminated food for 64 d and then to uncontaminated food for the
      next 64 d at three temperatures: 10, 15 and 20 degrees C. In this part of the
      study we found that the temperature under which the beetles were kept affected
      their respiration rates, and that effect of Ni on the respiration was significant
      only in animals originating from 20 degrees C. The results from both experiments
      indicate that negative effects of nickel appear only after relatively long
      exposure.

PMID- 18080186
TI  - Effects of bradykinin postconditioning on endogenous antioxidant enzyme activity
      after transient forebrain ischemia in rat.
AB  - Bradykinin is considered an important mediator of the inflammatory response in
      both the peripheral and the central nervous system and it has attracted recent
      interest as a potential mediator of brain injury following stroke. Bradykinin is
      recognized to play an important role in ischemic brain. We investigated the
      effect of bradykinin postconditioning on ischemic damage after 8 min of ischemia
      (four-vessel occlusion) and 3 days of reperfusion. Bradykinin was administered
      after 2 days of reperfusion at a dose of 150 microg/kg (i.p.). Catalase (CAT)
      activity was significantly increased in all examined regions (cortex, hippocampus
      and striatum) 3 days after 8 min of ischemia, but postconditioning decreased this
      activity below the control values. The total activity of superoxide dismutase
      (SOD) 3 days after ischemia was at control level with or without
      postconditioning. However, the analysis of individual SODs separately revealed
      interesting differences; while the activity of CuZnSOD was significantly
      decreased 3 days after ischemia, the activity of MnSOD was significantly
      increased compared to control levels. In both cases, postconditioning returned
      SOD activity to control levels. These findings are interesting because MnSOD is a
      mitochondrial enzyme and its activity in the cytosol suggests that a possible
      mechanism of protection provided by postconditioning could include prevention of
      release of mitochondrial proteins to the cytoplasm, resulting in protection
      against the mitochondrial pathway of apoptosis. 8 min of ischemia alone caused
      the degeneration of 52.37% neurons in the hippocampal CA1 region 3 days later.
      Bradykinin used as postconditioning 2 days after the same interval of ischemia
      enabled the survival of more than 97% of CA1 neurons. This study demonstrated
      that bradykinin postconditioning induces protection against ischemic brain injury
      and promotes neuronal survival.

PMID- 18080187
TI  - The contribution of the blood glutamate scavenging activity of pyruvate to its
      neuroprotective properties in a rat model of closed head injury.
AB  - The removal of excess glutamate from brain fluids after acute insults such as
      closed head injury (CHI) and stroke is expected to prevent excitotoxicity and the
      ensuing long lasting neurological deficits. Since blood glutamate scavenging
      accelerates the removal of excess glutamate from brain into blood and causes
      neuroprotection, we have evaluated here whether the neuroprotective properties of
      pyruvate could be partly accounted to its blood glutamate scavenging activity.
      The neurological outcome of rats after CHI improved significantly when treated
      with intravenous pyruvate (0.9 mmoles/100 g) but not with pyruvate administered
      together with glutamate. Pyruvate, at 5 micromole/100 g rat was neither
      protective not able to decrease blood glutamate but displayed the latter two
      properties when combined with 60 microg/100 g of glutamate-pyruvate transaminase.
      Since the neurological recovery from CHI was correlated with the decrease of
      blood glutamate levels, we conclude that pyruvate blood glutamate scavenging
      activity contributes to the spectrum of its neuroprotective mechanisms.

PMID- 18080188
TI  - Increased nitric oxide production and GFAP expression in the brains of influenza
      A/NWS virus infected mice.
AB  - The cause of influenza to the brain was investigated using the A/NWS/33 influenza
      virus infected BALB/c mouse model. NOS-2 mRNA levels in the infected mouse brain
      was greater than in control mice in all brain regions examined, particularly in
      the olfactory bulb and hippocampus by 1 day p.i. On the contrary, no differences
      in NOS-1 or NOS-3 mRNA levels were found between infected and control mice. There
      was also a marked increase in the levels of metabolites of nitric oxide in the
      olfactory bulb and hippocampus. Immunohistochemistry showed positive staining for
      anti-NOS-2 primarily in the hippocampus of infected mice. Further, anti-NOS-2 and
      GFAP staining was mostly found around capillary blood vessels of the hippocampus
      starting early in the course of the disease. These results indicate that the NWS
      enhances the activation of astrocytes and NOS-2 expression which in turn enhances
      NO production and the expansion of capillary blood vessels.

PMID- 18080189
TI  - Diphenyl diselenide-induced seizures in rat pups: possible interaction with
      glutamatergic system.
AB  - The aims of the present study were to investigate the possible involvement of
      glutamatergic system in seizures induced by diphenyl diselenide in rat pups
      (postnatal day, 12-14) and to evaluate the role of oxidative stress in seizures
      induced by diphenyl diselenide/glutamate. Glutamate (4 g/kg of body weight)
      administered in association with diphenyl diselenide (500 mg/kg of body weight)
      increased the latency for the appearance of the first seizure episode, reduced
      lipid peroxidation levels and catalase, Na+,K+-ATPase and delta-ALA-D activities.
      At the lowest dose (5 mg/kg of body weight), diphenyl diselenide reduced the
      appearance of seizure episodes induced by glutamate but did not alter the latency
      for the onset of the first episode. Glutamate uptake was inhibited in glutamate,
      diphenyl diselenide (the highest dose) and in the association of diphenyl
      diselenide (both doses) and glutamate groups. Pre-treatment with a N-methyl-D
      aspartate (NMDA) receptor antagonist, MK-801 (5S,10R-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine maleate), significantly prolonged the latency
      for the onset for the first convulsive episode. A non-NMDA receptor antagonist,
      DNQX (6,7-dinitroquinoxaline-2,3-dione), did not protect seizures induced by
      diphenyl diselenide. The results of the present study demonstrated that: (a) when
      diphenyl diselenide and glutamate were administered concomitantly in pups,
      glutamate was the main responsible for the neurotoxic effects; (b) oxidative
      stress was not involved in glutamate-induced seizures; (c) NMDA glutamatergic
      receptors, were at least in part, involved in diphenyl diselenide- induced
      seizures; and (d) diphenyl diselenide, at the lowest dose, protected seizures
      induced by glutamate.

PMID- 18080190
TI  - Chronic administration of lamotrigine downregulates COX-2 mRNA and protein in rat
      frontal cortex.
AB  - Chronic administration to rats of mood-stabilizers that are effective against
      mania in bipolar disorder, is reported to downregulate markers of the brain
      arachidonic acid cascade. We hypothesized that chronic administration of
      lamotrigine, which is used to treat depression and rapid cycling in bipolar
      disorder, might do so as well. Male CDF rats were administered a therapeutically
      relevant dose of lamotrigine (10 mg/kg) or vehicle intragastrically once daily
      for 42 days. Protein levels of isoforms of phospholipase A(2) (PLA(2)) and of
      cyclooxygenase (COX), and the mRNA level of COX-2, were quantified in the frontal
      cortex using immunoblotting and RT-PCR, respectively. Compared to vehicle-treated
      rats, chronic lamotrigine significantly decreased frontal cortex protein and mRNA
      levels of COX-2 without altering protein levels of the PLA(2) isoforms.
      Consistent with the hypothesis, lamotrigine and other mood-stabilizers have a
      common downregulatory action on COX-2 expression in rat brain, which may account
      in part for their efficacy in bipolar disorder.

PMID- 18080191
TI  - Liver transplantation in the setting of hepatocellular carcinoma and portal vein
      thrombosis: a challenging dilemma?
AB  - BACKGROUND: Portal vein thrombosis (PVT) represents a potentially unfavorable
      prognostic factor in liver transplantation (LT) for hepatocellular carcinoma
      (HCC). However, it is frequently difficult to establish preoperatively whether
      the thrombus is associated with tumor invasion or with stagnant flow. The purpose
      of this study was to further address this controversial issue. PATIENTS AND
      METHODS: We evaluated 12 consecutive patients who underwent liver transplantation
      for HCC in the setting of PVT. RESULTS: The origin of PVT in HCC patients could
      be accurately evaluated in 58% of the patients. Forty-two percent of patients had
      no evident portal vein invasion and only 17% of cases had tumor thrombi. One
      third of patients experienced tumor recurrence within the first posttransplant
      year, and one-third of patients became long-term survivors (median survival of 36
      months) with no evidence of tumor recurrence. One-year survival was 92%. Nine
      patients are currently alive after a median follow-up period of 25 months.
      CONCLUSIONS: PVT in the setting of HCC is characterized by poor patient outcome.
      However, a respectable number of instances are not accurately evaluated
      preoperatively, making the decision to exclude these patients from LT sometimes a
      challenging dilemma.

PMID- 18080192
TI  - Endoscopic patterns and histopathological features after eradication therapy in
      Helicobacter pylori-associated nodular gastritis.
AB  - The endoscopic finding of nodular gastritis (NG) is highly associated with
      presence of Helicobacter pylori infection. How the endoscopic patterns and
      histopathology of NG change after eradication of H. pylori is unclear. Twenty-one
      adults (3 men and 18 women) with H. pylori-associated NG found on endoscopy were
      enrolled for this study. The histological findings included gastritis activity,
      bacterial colonization, and lymphoid follicles. Repeat endoscopy for the
      endoscopic as well as histopathological features of gastric biopsy specimens was
      performed 2 months later after eradication treatment. H. pylori was successfully
      eradicated in 19 patients. Endoscopic NG disappeared in 12, improved in 5, and
      was unchanged in 4. After treatment, there was significant improvement in scores
      for gastritis activity [P < 0.001, 95% confidence interval (CI) 1.31-1.91],
      bacterial colonization (P < 0.001, 95% CI 0.71-1.14) and follicular gastritis (P
      = 0.047, 95% CI 0.04-0.52), primarily among patients whose endoscopic pattern
      resolved completely. The disappearance of nodularity on endoscopy was accompanied
      by a decrease in follicular gastritis score.

PMID- 18080193
TI  - Immunologic function of dendritic cells in esophageal cancer.
AB  - Esophageal cancer is one of the frequently occurring malignant cancers. The
      current therapy, including surgery, chemotherapy, radiotherapy, or a combination,
      is only to palliate the symptoms; overall the prognosis is poor. The
      immunotherapy of dendritic cells for esophageal cancer is a valuable method.
      Dendritic cells existing in the esophageal tissues play an important role in the
      host's immunosurveillance against cancer as the professional antigen-presenting
      cells. This review concerns the immunology of dendritic cells in esophageal
      cancer; it describes the expression of DCs in the normal esophageal tissues and
      benign disease of esophagus, relations between the DCs and cancer development in
      esophageal cancer, and the DC-based approach to establish treatment for
      esophageal cancer.

PMID- 18080194
TI  - Deficiency of 6B11+ invariant NK T-cells in celiac disease.
AB  - Immunoregulatory NK T-cells are deficient in certain autoimmune diseases. The
      purpose of this study was to investigate any deficiency of immunoregulatory NK T
      cells in celiac disease. NK T-cells were identified by flow cytometry with 6B11
      and V alpha 24 markers in blood from 18 normal and 12 celiac subjects. Blood
      mononuclear cells were stimulated with anti-CD3/CD28 antibodies and intracellular
      cytokines assessed at 4 h in seven normal and eight celiac subjects. V alpha
      24/GAPDH mRNA was quantitated in duodenal biopsies by real time PCR in 17 control
      and 13 celiac subjects. NK T-cells in celiac subjects were reduced to 30% of
      those in normal subjects. Intracellular IL-4, IL-10 and IL-13 increased
      significantly by 33-41% in normal subjects, but did not change in celiac
      subjects. V alpha 24/GAPDH mRNA from celiac subjects was reduced to 5% of levels
      in control subjects. We conclude that immunoregulatory NK T-cells are deficient
      in celiac disease.

PMID- 18080195
TI  - Gastric changes following colchicine therapy in patients with FMF.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is also called recurrent
      polyserositis. The salient features of this disease include brief recurrent
      episodes of peritonitis, pleuritis, and arthritis, which are usually associated
      with fever. Colchicine is highly effective in the treatment of FMF and in
      preventing the development of recurrent attacks and amyloidosis, and it is
      essential to make the correct diagnosis and institute daily therapy with
      colchicine (0.5-0.6 mg bid). Colchicine is used to treat a variety of conditions
      but it is known to have gastrointestinal (GI) side effects. In this study,
      effects of colchicines on the gastrointestinal tract were evaluated in patients
      with FMF treated with colchicine. METHODS: Biopsies were reviewed from 43
      patients attending Ain Shams University Hospital (Egypt) who were diagnosed with
      FMF and treated with colchicine. One-hundred and twelve GI biopsies, obtained
      over a 14-year period, were reviewed. This included biopsies from stomach body
      (38), stomach antrum (50), and colon (24). In addition, gastric biopsies were
      reviewed from 17 control patients who did not have FMF and were not on
      colchicine. RESULTS: Three patients known to have FMF and on colchicine therapy
      showed typical histological features of colchicine (metaphase mitoses, epithelial
      pseudoproliferation, mucin depletion, and frequent apoptosis). These features
      were seen only in gastric antral biopsies and not in colonic biopsies. None of
      the control group showed the characteristic morphological features of colchicine
      toxicity. CONCLUSION: This is the first report of histological changes seen in
      the stomach following colchicine therapy. In contrast with previous reports, we
      did not find any definitive change in the large intestine. Our data show that
      gastric changes can be encountered in symptomatic patients who have recently had
      colchicine. If these finding are seen histologically, they merit correlation with
      the clinical impression and should not be interpreted as toxicity in isolation.

PMID- 18080196
TI  - Helicobacter pylori stool antigen (HpSA) tests in children before and after
      eradication therapy: comparison of rapid immunochromatographic assay and HpSA
      ELISA.
AB  - The rapid immunochromatography for Helicobacter pylori (H. pylori) stool antigen
      (rapid HpSA) test is a recently-developed method for detection of H. pylori
      infection. The objective of this study was to assess the pre and post-eradication
      diagnostic accuracy of the rapid HpSA test compared with the conventional HpSA
      immunoassay (HpSA ELISA) in children. Sensitivity, specificity, positive
      predictive value, and negative predictive value for the rapid HpSA test were
      94.6, 98.4, 94.6, and 98.4%, respectively, and those for the HpSA ELISA were
      94.6, 96.1, 87.5, and 98.4%, respectively. No significant difference was observed
      between the sensitivity and specificity of the two HpSA tests in children (P =
      1.000 and P = 0.250) or the sensitivity and specificity of the two HpSA tests pre
      and post-eradication therapy (P = 1.000 and P = 1.000). The rapid HpSA and HpSA
      ELISA are reliable methods of detection of H. pylori infection in the pediatric
      population before and after eradication therapy.

PMID- 18080197
TI  - Acid-suppression therapy offers varied laryngopharyngeal and esophageal symptom
      relief in laryngopharyngeal reflux patients.
AB  - It is widely accepted that laryngopharyngeal reflux requires more aggressive and
      prolonged therapy than gastro-esophageal reflux disease. Otolaryngologists often
      observe that laryngopharyngeal symptoms, such as throat clearing, hoarseness,
      cough, and globus pharyngeus, are slower to resolve than esophageal symptoms,
      such as heartburn and regurgitation. The aim of this was to provide empirical
      evidence to support this observation and to carry out a detailed investigation of
      the differences between these symptoms. Forty-five patients with
      laryngopharyngeal and esophageal symptoms received acid-suppression therapy that
      involved the continuous administration of a proton-pump inhibitor for up to 6
      months. We investigated the differences in response to acid-suppression therapy
      between patients suffering from laryngopharyngeal and esophageal symptoms,
      respectively, who received upper gastrointestinal endoscopy and were assayed for
      serum Helicobacter pylori antibodies. The significance of the rate of symptom
      improvement was estimated by Kaplan-Meier analysis and the logrank test.
      Laryngopharyngeal symptoms improved significantly more slowly than esophageal
      symptoms following acid-suppression therapy (49.8 vs. 78.3%, 60 days after the
      start of acid suppression; P = 0.003). These differences were observed both in
      patients with erosive esophagitis (P = 0.008) and in H. pylori-seronegative
      patients (P = 0.001).

PMID- 18080198
TI  - Dendritic cells and toll-like receptors 2 and 4 in the ileum of Crohn's disease
      patients.
AB  - We investigated myeloid-dendritic cell (DC) marker and Toll-like receptor (TLR)-2
      and 4 distributions in ileal samples from Crohn's disease (CD) patients (n = 14)
      and controls (n = 13). In controls, no TLR-2+ cells were observed, and higher
      numbers of TLR-4+ and DC-SIGN+ cells (P < 0.01) were detected in ileal samples
      when compared versus colonic tissues. In non-inflamed CD ileum, TLR-4+ and DC
      SGN+ cells were depleted from superficial areas of the villus, and a significant
      CD1a+ cell infiltration (P < 0.01) was observed when compared to ileal controls
      and non-inflamed colonic CD samples. In inflamed CD ileum, DC-SIGN+, CD1a+, TLR
      4+and few TLR-4+DC-SIGN+ cells were detected as well as CD83 depletion. No
      correlation between TLR-2 and DC markers was detected in CD samples. A unique
      distribution of myeloid-DC markers characterized the CD ileum. Also, the presence
      of significant amounts of ileal CD1a+ cells may provide a relevant DC-mediated
      mechanism for antigen recognition in the pathogenesis of CD.

PMID- 18080199
TI  - Piloting the time diary method among Honduran immigrants: gendered time use.
AB  - By studying time allocation, a factor implicitly linked to health by structuring
      individuals' physical exercise, leisure, sleep, and access to care, we can better
      understand behavioral mechanisms to improve health in minority populations. We
      piloted the time diary method in a Honduran immigrant community to assess time
      spent in personal and interpersonal responsibilities, and we examined how these
      patterns varied by gender. In the context of participatory ethnography, 34 urban
      Honduran immigrants were recruited and followed over 7 days. Respondents reported
      activities by 30-min periods for seven 24-h days. Observed respondent-level
      reliability exceeded 0.7 for time spent in commuting, care work, family
      responsibility, and individual leisure, showing better results than 3- or 10-day
      tracking schemes. Gender differences in time allocation patterns were also
      observed. We argue that understanding time use patterns will elucidate gendered
      disparities in health outcomes associated with physical mobility, and in access
      to health care.

PMID- 18080200
TI  - Arab American immigrants in New York: health care and cancer knowledge,
      attitudes, and beliefs.
AB  - Arab immigrants living in the United States total between 1.5 million and 3.5
      million, and have been growing in number each decade. New York's Arab population,
      at 405,000, ranks third in the U.S. after California and Michigan. Despite the
      large numbers, little health research has focused on this population. Data about
      the cancer incidence, mortality, and screening practices of Arab Americans is
      overwhelmingly lacking. To better understand the health care and cancer
      knowledge, attitudes, and beliefs of Arab American immigrants, five single-gender
      focus groups were convened with Arab men and women in New York City. Attention
      was given to factors that act as barriers to utilization of general health care
      services, and of cancer prevention, treatment, and support services. The data
      revealed the importance of providing culturally and linguistically appropriate
      health interventions in partnership with trusted community leaders, and the need
      for follow-up research of this understudied immigrant population.

PMID- 18080201
TI  - Nano-aquarium for dynamic observation of living cells fabricated by femtosecond
      laser direct writing of photostructurable glass.
AB  - We demonstrate the fabrication of three-dimensional (3-D) hollow microstructures
      embedded in photostructurable glass by a nonlinear multiphoton absorption process
      using a femtosecond (fs) laser. Fs laser direct writing followed by annealing and
      successive wet etching in dilute hydrofluoric (HF) acid solution resulted in the
      rapid manufacturing of microchips with 3-D hollow microstructures for the dynamic
      observation of living microorganisms and cells in fresh water. The embedded
      microchannel structure enables us to analyze the continuous motion of Euglena
      gracilis. A microchamber with a movable microneedle demonstrates its ability for
      the elucidation of the information transmission process in Pleurosira laevis.
      Such microchips, referred to as nano-aquariums realize the efficient and highly
      functional observation of microorganisms and cells.

PMID- 18080203
TI  - Has the surge in media attention increased public awareness about colorectal
      cancer and screening?
AB  - The Centers for Disease Control and Prevention's Screen for Life campaign in
      March 1999 followed by the creation of National Colorectal Cancer Awareness Month
      in March 2000 heralded a surge in media attention to promote awareness about CRC
      and stimulate interest in screening. Our objective was to assess whether these
      campaigns have achieved their goal of educating the public about CRC and
      screening. The study sample was comprised of mostly unscreened, average-risk,
      English-speaking patients aged 50-75 years seen in an urban primary care setting.
      Knowledge was assessed using a 12-item true/false questionnaire based primarily
      on the content of key messages endorsed by the National Colorectal Cancer
      Roundtable (Cancer 95:1618-1628, 2002) and adopted in many of the media
      campaigns. Multiple linear regression was performed to identify demographic
      correlates of knowledge. A total of 356 subjects (83% <age 65, 58% female, 60%
      Black, 7% Hispanic, 60% <or=high school degree, 31% prior FOBT ) were surveyed.
      Most respondents (>or=67%) were aware of who gets CRC, age to initiate screening,
      the goals of screening and potential benefits. Fewer were aware that removing
      polyps can prevent CRC and that both polyps and CRC may be asymptomatic.
      Knowledge scores were lower among Blacks and those with a high school degree or
      less. Race and education were independent correlates of knowledge. These data
      suggest that recent media campaigns have been effective in increasing public
      awareness about CRC risk and screening but important gaps in knowledge remain.

PMID- 18080204
TI  - Previous cancer screening behavior as predictor of endoscopic colon cancer
      screening among women aged 50 and over, in NYC 2002.
AB  - Colon cancer screening rates in women are low. Whether screening for breast and
      cervical cancer is associated with colon cancer screening behavior is unknown but
      could provide linkage opportunities. To identify the extent to which both breast
      and cervical cancer screening increases uptake of colon cancer screening among
      women in New York City. Women at least 50 years old completed questionnaires for
      the New York Cancer Project. Analyses compared rates of endoscopic colon cancer
      screening with adherence to screening recommendations for breast and cervical
      cancer. Of the 3,386 women, 87.8% adhered to breast and cervical cancer screening
      guidelines, yet only 42.1% had received endoscopic colon cancer screening. Most
      women with colon cancer screening (95%) also reported past mammogram and Pap
      smear. In multivariable analysis, women who adhered to the other two procedures
      were more likely to have had colon cancer screening than women with no prior
      history (OR = 4.4; CI = 2.36, 8.20), after accounting for age, race/ethnicity,
      insurance status, family history of cancer and income. Significant predictors of
      endoscopic colon cancer screening included: age over 65 years (OR = 1.63; CI =
      1.23, 2.15) with 50-65 years old as the reference, any health insurance (OR =
      2.18; CI = 1.52, 3.13) and a family history of cancer (OR = 1.38; CI = 1.17,
      1.61). Colorectal cancer screening remains low, even among women who undergo
      other cancer screening tests. Opportunities to link cancer screening tests to
      encourage colon cancer screening merit closer attention.

PMID- 18080205
TI  - Patients' understanding of the regulation of dietary supplements.
AB  - The Dietary Supplement Health and Education Act (DSHEA) permits manufacturers to
      sell products without providing pre-market evidence of safety or efficacy. One
      fundamental reason for the passage of the DSHEA was to empower consumers to make
      their own choices, free from governmental restriction. Yet, little is known about
      the public's understanding of the supplement regulatory process. We undertook a
      study to assess patients' knowledge regarding governmental oversight of product
      marketing and advertising. A survey of 300 adult patients from the Baltimore
      Metropolitan area was administered after showing participants an advertisement
      for a dietary supplement. Patients were asked questions regarding their
      understanding of federal regulation of the advertised product. A total of 52% of
      respondents were unaware that the dietary supplement had not been approved by the
      government while 63% were unaware that the advertisement for that supplement had
      not been pre-approved. Factors associated with a lack of understanding of the
      product approval process included lower education level (OR 2.52; 95% CI 1.52
      4.19) and non-Caucasian race (OR 1.99; 95% CI 1.17-3.36). Lower education level
      was also associated with confusion regarding the advertisement approval process
      (OR 2.60; 95% CI 1.48-4.57). Based on these results, patients seem unclear about
      the government's role in the regulation of dietary supplements. Educational
      efforts should be geared towards clarifying these issues.

PMID- 18080206
TI  - Survey of pest infestation, asthma, and allergy in low-income housing.
AB  - Low-income housing often has multiple indoor health risks. Among them, pest
      infestation, pesticide use, and pest allergens are recognized as common risks
      which affect residents' health. Cockroach and rodent allergens are associated
      with morbidity and mortality of asthmatics. To characterize the levels of pest
      infestation, residents' attitudes toward pest control, and the relationships
      among cockroaches, mice, cockroach allergen level, asthma and allergy rate in
      public housing, we interviewed residents from 358 randomly selected apartments in
      Gary, Indiana and assessed the environmental conditions. Dust samples were
      collected from 101 apartment kitchen floors to analyze for cockroach allergen
      (Bla g 1 and Bla g 2) levels. Eighty one percent of the apartments were found
      infested by cockroaches, mice, ants, spiders, or flies. In the 101 apartments
      evaluated, 98% of the kitchen dust samples had detectable levels of Bla g 1
      allergen (>or=0.4 U/g), 52% had >or=2 U/g, and 33% had >or=8 U/g of Bla g 1.
      Among the 1,173 residents, 13% and 9% had physician-diagnosed asthma and allergy,
      respectively. Existence of diagnosed asthmatic was positively correlated with
      mouse infestations.

PMID- 18080208
TI  - Determination of myocardial energetic output for cardiac rhythm pacing.
AB  - This research is aimed to the determination of the changes in the cardiac
      energetic output for three different modes of cardiac rhythm pacing. The clinical
      investigation of thirteen patients with the permanent dual-chamber pacemaker
      implantation was carried out. The patients were taken to echocardiography
      examination conducted by way of three pacing modes (AAI, VVI and DDD). The
      myocardial energetic parameters-the stroke work index (SWI) and the myocardial
      oxygen consumption (MVO2) are not directly measurable, however, their values can
      be determined using the numerical model of the human cardiovascular system. The
      24-segment hemodynamical model (pulsating type) of the human cardiovascular
      system was used for the numerical simulation of the changes of myocardial
      workload for cardiac rhythm pacing. The model was fitted by well-measurable
      parameters for each patient. The calculated parameters were compared using the
      two-tailed Student's test. The differences of SWI and MVO2 between the modes AAI
      and VVI and the modes DDD and VVI are statistically significant (P<0.05). On the
      other hand, the hemodynamic effects for the stimulation modes DDD and AAI are
      almost identical, i.e. the differences are statistically insignificant (P>0.05).

PMID- 18080207
TI  - The associations between life satisfaction and health-related quality of life,
      chronic illness, and health behaviors among U.S. community-dwelling adults.
AB  - The primary purpose of this article was to examine the associations between life
      satisfaction level and health-related quality of life (HRQOL), chronic illness,
      and adverse health behaviors among adults in the U.S. and its territories. Data
      were obtained from the 2005 Behavioral Risk Factor Surveillance System, an
      ongoing, state-based, random-digit telephone survey of the noninstitutionalized
      U.S. population aged >or=18 years. An estimated 5.6% of U.S. adults (about 12
      million) reported that they were dissatisfied/very dissatisfied with their lives.
      As the level of life satisfaction decreased, the prevalence of fair/poor general
      health, disability, and infrequent social support increased as did the mean
      number of days in the past 30 days of physical distress, mental distress,
      activity limitation, depressive symptoms, anxiety symptoms, sleep insufficiency,
      and pain. The prevalence of smoking, obesity, physical inactivity, and heavy
      drinking also increased with decreasing level of life satisfaction. Moreover,
      adults with chronic illnesses were significantly more likely than those without
      to report life dissatisfaction. Notably, all of these associations remained
      significant after adjusting for sociodemographic characteristics. Our findings
      showed that HRQOL and health risk behaviors varied with level of life
      satisfaction. As life satisfaction appears to encompass many individual life
      domains, it may be an important concept for public health research.

PMID- 18080209
TI  - Method for measuring substrate preferences by individual members of microbial
      consortia proposed for bioaugmentation.
AB  - In this study we used the assimilation of isotope labeled CO(2) to measure the
      substrate preferences by two different bioaugmentation mixtures proposed for
      bioremediation of diesel oil contamination. All active microorganisms assimilate
      CO(2) in various carboxylation processes involved in growth. The CO(2)
      assimilation by the two mixtures was measured upon addition of glucose, diesel
      oil or specific compounds present in diesel oil (naphthalene, toluene,
      hexadecane, and octane). It was shown that within short term incubations with
      diesel oil (<5 h), one bioaugmentation mixture was superior to the other
      regarding the assimilation of CO(2). This observation was confirmed in a labor
      intensive long term microcosm study (60 days). The applied method open various
      possibilities for fast pre-testing of substrate-preferences by microbial
      bioaugmentation mixtures without microcosm experiments, on-site tests, and
      complicated chemical analysis. This study also demonstrates the possibility to
      obtain further information on the substrate preferences at a single cell level of
      phylogenetically defined microbial subgroups in bioaugmentation mixtures, based
      on combined analyses of microautoradiography and fluorescence in situ
      hybridization.

PMID- 18080210
TI  - A mathematical model of fatigue in skeletal muscle force contraction.
AB  - The ability for muscle to repeatedly generate force is limited by fatigue. The
      cellular mechanisms behind muscle fatigue are complex and potentially include
      breakdown at many points along the excitation-contraction pathway. In this paper
      we construct a mathematical model of the skeletal muscle excitation-contraction
      pathway based on the cellular biochemical events that link excitation to
      contraction. The model includes descriptions of membrane voltage, calcium cycling
      and crossbridge dynamics and was parameterised and validated using the response
      characteristics of mouse skeletal muscle to a range of electrical stimuli. This
      model was used to uncover the complexities of skeletal muscle fatigue. We also
      parameterised our model to describe force kinetics in fast and slow twitch fibre
      types, which have a number of biochemical and biophysical differences. How these
      differences interact to generate different force/fatigue responses in fast- and
      slow- twitch fibres is not well understood and we used our modelling approach to
      bring new insights to this relationship.

PMID- 18080211
TI  - Seasonal change and correlation with environmental parameters for 2-MIB in Feng
      Shen Reservoir, Taiwan.
AB  - Two common drinking water earthy/musty odorants, 2-methyl-isoborneol (2-MIB) and
      trans-1,10-dimethyl-trans-9-decalol (geosmin), were monitored and analyzed for
      their correlation with environmental conditions in Feng-Shen Reservoir (FSR),
      Taiwan. Long-term monitoring results, from December 2000 to July 2003, indicated
      that 2-MIB was present in the reservoir at concentrations between 10 and 200 ng
      L(-1), and those of geosmin were always smaller than 10 ng L(-1). The 2-MIB
      concentrations followed a trend of higher concentrations during the warm seasons.
      After being analyzed with 10 water quality and three meteorological parameters, 2
      MIB concentration was found to correlate with corresponding air and water
      temperatures. An analysis of air temperature history versus 2-MIB concentration
      in FSR suggested that 2-MIB concentration was best correlated with the mean of
      average daily temperature from 1 to 9 days before sampling, with R (2) = 0.90.
      This correlation was further employed to predict the 2-MIB concentration observed
      during another sampling period in FSR. A similar degree of fit was observed
      between predictions and experimental data, suggesting the potential applicability
      of the approach. In addition to the effect of temperature, heavy rainfalls that
      occurred before the sampling time may also reduce the 2-MIB concentration in the
      reservoir. A short-term continuous monitoring of the odorants for 32 h showed
      that both geosmin and 2-MIB concentrations in the reservoir remained almost
      constant, with only about a 10% difference during the sampling period. This may
      suggest that the odorants were uniformly distributed in the water near the
      sampling location in the reservoir.

PMID- 18080212
TI  - Comparative proteomic analysis of livers from ketotic cows.
AB  - The aim of this study was to examine molecular pathways activated in the liver of
      the ketotic cow to gain further understanding of the pathogenic effects of
      ketosis. We used two-dimensional-electrophoresis (2D-E) and matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF-TOF) tandem mass spectrometry to
      compare the liver proteomic profile between ketotic and normal cows. Thirty-eight
      different proteins were identified between these groups by 2D-E gel. These
      proteins play a role in energy metabolism, carbohydrate degradation, fatty acid
      metabolism, amino acid metabolism, antioxidation, cell structure, nucleotide
      metabolism, and protein metabolism. This is the first time the majority of these
      proteins have been reported in cow ketosis. Possible explanations for the
      differential expression patterns and their relevance to the pathogenesis of
      ketosis in the cow are discussed. This study is the first to provide a detailed
      insight into protein expression patterns in the liver of the ketotic cow, and the
      different proteins involved in the pathogenesis of bovine ketosis.

PMID- 18080213
TI  - Lower extremity peripheral vein bypass graft wall thickness changes demonstrated
      at 1 and 6 months after surgery with ultra-high spatial resolution black blood
      inner volume three-dimensional fast spin echo magnetic resonance imaging.
AB  - OBJECTIVE: To demonstrate lower extremity peripheral vein bypass graft wall
      thickness changes over time in a patient using very high spatial resolution
      cardiac gated, black blood inner volume three-dimensional (3D) fast spin echo
      (FSE) magnetic resonance imaging (MRI). CASE REPORT: A 52-year-old diabetic man
      with a history of hyperlipidemia underwent uncomplicated bypass grafting for an
      asymptomatic 5.2 cm popliteal artery aneurysm using reversed great saphenous
      vein. A segment of the bypass graft was studied at 1 and 6 months after surgery
      with cardiac gated inner volume 3D-FSE imaging with non-interpolated 0.195 mm(3)
      voxel volumes (0.3125 x 0.3125 x 2 mm). T1- and T2-weighted images were acquired
      in 10 min per contrast weighting. Graft imaging at one month after implantation
      illustrates expansion of the outer wall of the graft that partially resolves 5
      months later. CONCLUSION: In this patient, expansion of the lower extremity
      peripheral bypass graft wall can be characterized in clinical scan times with a
      3D-FSE MRI protocol using highly selective inner volume excitation followed by
      non-selective refocusing pulses. The resulting 3D images can potentially be used
      to study the biology of the vessel wall.

PMID- 18080214
TI  - An 18-item standardized Asthma Quality of Life Questionnaire-AQLQ(S).
AB  - The purpose of the present study was to examine the validity and reliability of
      the Asthma Quality of Life Questionnaire-AQLQ(S) in a sample of 160 Greek
      patients with asthma. Following evidence for sample-specific validity, the
      AQLQ(S) model was examined through exploratory and confirmatory factor analysis.
      An 18-item AQLQ(S) with the four factors of symptoms, activity limitations,
      sleep, and exposure in environmental stimuli fits the data (chi(2)/df ratio =
      2.26, NNFI = 0.92, CFI = 0.94, SRMR = 0.05). The 18-item AQLQ(S) showed a high
      internal consistency (Cronbach' a coefficient ranged from 0.83 to 0.96) and high
      9-week test-retest reliability (overall r = 0.88, ICC = 0.94). Responsiveness was
      confirmed throughout 2X2 ANOVA and 2X2 MANOVA, with respect to the total score (F
      = 42.30, P < 0.05), and the four AQLQ(S) factors (Wilks' lambda = 0.68, F =
      17.59, P < 0.05). The cross-sectional correlations between the 18-item AQLQ(S)
      and the: (1) FEV1% predicted and (2) Borg scale were low and moderately high,
      respectively. In conclusion, the 18-item AQLQ(S) derived from exploratory and
      confirmatory factor analysis appeared to have sufficient construct validity,
      cross-sectional validity, responsiveness, satisfactory test-retest reliability
      and internal consistency evidence for the Greek sample of adults with asthma.

PMID- 18080215
TI  - Analyzing growth and change: latent variable growth curve modeling with an
      application to clinical trials.
AB  - OBJECTIVE: Typical methods of analyzing data from clinical trials have
      shortcomings, notably comparisons of group means, use of change scores from pre-
      and post-treatment assessments, ignoring intervening assessments, and focusing on
      direct effects of treatment. A comparison of group means disregards the
      likelihood that individuals have different trajectories of change. Moreover,
      change scores ignore intervening assessments that may provide useful information
      about change. This paper compares results from traditional regression-based
      methods for analyzing data from a clinical trial (e.g., regression with change
      scores) with those of latent growth curve modeling (LGM). METHODS: LGM is a
      method that uses structural equation modeling techniques to model individual
      change, assess treatment effects and the relationship among multiple outcomes
      simultaneously, and model measurement error. The consequence is more precise
      parameter estimates while using data from all available time points. RESULTS:
      Results demonstrate that LGM can yield stronger parameter estimates than the
      traditional regression-based approach and explain more variance in the outcome.
      In trials where there is a true effect, but it is non-significant or marginally
      significant using the traditional methods, LGM may provide evidence of this
      effect. CONCLUSIONS: Analysts are encouraged to consider LGM as an additional and
      informative tool for analyzing clinical trial or other longitudinal data.

PMID- 18080217
TI  - Human uridine-cytidine kinase phosphorylation of ribavirin: a convenient method
      for activation of ribavirin for conjugation to proteins.
AB  - Ribavirin is a synthetic nucleoside analog that is used for the treatment of
      hepatitis C virus (HCV) infection. Its primary toxicity is hemolytic anemia,
      which sometimes necessitates dose reduction or discontinuation of therapy.
      Selective delivery of ribavirin into liver cells would be desirable to enhance
      its antiviral activity and avoid systemic side effects. One approach to liver
      specific targeting is conjugation of the ribavirin with asialoglycoprotein that
      is taken up specifically by liver cells. Human uridine-cytidine kinase-1 (UCK-1)
      was used for ribavirin phosphorylation to its monophosphate form. 1-Ethyl-3
      diisopropylaminocarbodiimide (EDC) was used as a coupling agent. The best results
      were obtained using direct conjugation protocol with a molar ratio of 6.5
      ribavirin monophosphate (RMP) molecules per one asialoorosomucoid (AsOR)
      molecule. Our findings show that ribavirin is a potential substrate of UCK-1, and
      RMP formed could be chemically coupled to AsOR to form a conjugate for liver
      specific targeting.

PMID- 18080216
TI  - Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus
      sporadic breast cancer susceptibility and survival.
AB  - Identifying genes associated with familial inheritance of breast cancer continues
      to be a major goal of current research as the known high penetrance genes could
      be attributable for only a small percentage of the risk. So, it is hypothesized
      that the low penetrance genes may also modify the risk for familial breast
      cancer. In the present case-control study, undertaken to examine the influence of
      polymorphisms of GSTs in familial and sporadic breast cancer susceptibility, 597
      women including 222 sporadic breast cancer patients, 125 familial breast cancer
      patients and 250 females with no history of cancer as controls were genotyped by
      PCR based methods. Odds Ratios (ORs) and 95% Confidence Intervals (95%CIs) were
      calculated by unconditional logistic regression adjusted to age. Interestingly,
      GSTM1 deletion was found to be significantly associated only with familial breast
      cancer (OR = 2.0; 95%CI = 1.252-3.128) while GSTT1 was associated only with
      sporadic breast cancer (OR = 2.3; 95%CI = 1.336-3.970). GSTP1 Ile105Val
      polymorphism was associated neither with sporadic nor familial breast cancer
      susceptibility (P value > 0.05). The GST genotypes did not have any effect on the
      survival of both familial and sporadic breast cancer patients. However, familial
      breast cancer patients with GSTM1 null genotype had a relative risk of 0.42
      (95%CI = 0.18-0.97) for an advanced disease stage. The results indicate that, in
      addition to the known high penetrance genes, certain low penetrance genes may
      also play a role, in the familial inheritance of breast cancer. It is also
      noticed that all the polymorphisms associated with sporadic breast cancer are not
      associated with familial breast cancer.

PMID- 18080218
TI  - Molecular and biochemical characterization of an endochitinase (ChiA-HD73) from
      Bacillus thuringiensis subsp. kurstaki HD-73.
AB  - An endochitinase gene (chiA-HD73) from the insecticidal bacterium Bacillus
      thuringiensis subsp. kurstaki HD-73 was cloned, sequenced, and expressed in
      Escherichia coli DH5alphaF'. The chitinase activity of the encoded protein was
      studied in assays with different fluorogenic substrates. The chiA-HD73 gene
      contained an open-reading frame that encoded an endochitinase with a deduced
      molecular weight and an isoelectric point of, respectively, 74.5 kDa and 5.75. A
      putative signal peptide with cleavage sites for both Gram-positive and Gram
      negative bacteria was identified. Comparison of ChiA-HD73 with other chitinases
      revealed a modular structure composed of a catalytic domain and a putative chitin
      binding domain. ChiA-HD73 hydrolyzed both tetrameric and trimeric fluorogenic
      substrates, but not a chitobiose analog substrate, suggesting that the activity
      of ChiA-HD73 is mainly endochitinolytic. In addition, ChiA-HD73 showed high
      enzymatic activity within a broad pH range (pH 4-10), with a peak activity at pH
      6.5. The optimal temperature for enzymatic activity was observed at 55 degrees C.
      Its activity in a broad range of temperatures and pH suggests ChiA-HD73 could
      have biotechnological applications in insect control, particularly in synergizing
      the insecticidal crystal protein toxins of B. thuringiensis.

PMID- 18080222
TI  - [Benchmarking in gastrointestinal endoscopy].

PMID- 18080223
TI  - [Benchmarking in gastrointestinal endoscopy].
AB  - Quality and costs of endoscopic procedures in gastroenterology have recently come
      into focus of professionals and patients alike. The project presented here
      combines benchmarking of indicators of quality and simultaneous assessment of
      costs in departments of endoscopy. In all 9400 examinations from 14 departments
      were analysed. First and most obvious results are presented: the machine-readable
      data sheet was filled out correctly in 95 % (compulsory data fields); endoscopy
      costs differed by factor two for diagnostic gastroscopy and by factor five for
      therapeutic ERCP; in some departments a polypectomy was performed in up to every
      second diagnostic colonoscopy while in others polypectomy occurred only in 10 %
      in some departments patient monitoring like pulse oxymetry was used only in half
      of the procedures. Interpretation of the data requires further validation by
      resumption of the project to obtain more data from possibly more departments.

PMID- 18080224
TI  - Successful treatment of steroid refractory active ulcerative colitis with natural
      interferon-beta--an open long-term trial.
AB  - INTRODUCTION: In some steroid refractory patients with active ulcerative colitis
      (UC), treatment with immunosuppressive agents, such as cyclosporin, azathioprine
      or 6-mercaptopurin is effective. However, there are patients who fail to respond
      to these treatment options or who cannot tolerate them. Application of natural
      interferon-beta (nIFN-beta) may offer an alternative. Following our positive
      results with nIFN-beta in a previously published open-labeled study, the present
      study was designed as an extension with the hypothesis that administration of
      higher dosage of nIFN-beta (1.0 vs. 0.5 MIU) could result in fewer relapse
      events. PATIENTS AND METHODS: 46 steroid refractory patients with active UC and a
      mean clinical activity index (CAI) of 13.2 +/- 3.7 (range 9-23) were treated with
      nIFN-beta in addition to existing basic medication (5-ASA/SASP plus
      corticosteroids). During an induction period of eight weeks, 18 patients (group
      A) received 0.5 MIU nIFN-beta daily and 28 patients (group B), 1.0 MIU nIFN-beta
      daily intravenously as a bolus injection. Patients who achieved complete
      remission (decrease of CAI to < or = 4) during the induction period received
      maintenance therapy with nIFN-beta at the same dose level three times a week and
      corticosteroids were withdrawn. Remissions and maintenance of remissions were
      evaluated. RESULTS: In both groups, a comparable number of complete remissions
      occurred during the induction period: in 16 / 18 patients (89 %) in group A and
      in 24 / 28 patients (86 %) in group B. Duration of maintenance treatment was 60.0
      +/- 90.0 weeks in group A and 52.7 +/- 9.6 weeks in group B. Under this
      treatment, relapses (increase of CAI to > or = 6) occurred in 5 / 16 patients (31
      %) vs. 1 / 24 patients (4 %) (p < or = 0.05). Hence, regarding maintaining
      remissions, the 1.0 MIU group outscored the 0.5 MIU group. Apart from known flu
      like side effects, the therapy was well tolerated by all patients in both groups.
      CONCLUSION: nIFN-beta may be a safe and effective alternative to induce and
      maintain remissions in patients with steroid refractory active UC. To validate
      the presented results, its effect has to be investigated in a randomized, placebo
      controlled dose-finding trial.

PMID- 18080225
TI  - [Primary liposarcoma of the liver--a rare mesenchymal tumor].
AB  - Primary sarcoms of the liver are rare. Most often angiosarcomas have been
      reported. Primary liposarcoma of the liver is extremely rare. We report a case of
      primary liposarcoma of the liver in a 48-year-old woman and compare it with the
      13 cases found in the literature. Histologic analysis showed a well
      differentiated liposarcoma. The treatment of choice is wide local tumor
      resection.

PMID- 18080226
TI  - [Autoimmune pancreatitis with normal IgG4-Levels: 4 case reports and review of
      the literature].
AB  - We report four cases of autoimmune pancreatitis in an 18-, a 22- and a 26-year
      old male patient and a 20-year-old female patient. The 20-year-old female patient
      was admitted to the hospital with upper abdominal pain and jaundice, the 18-year
      old patient with recurrent acute pancreatitis and cholestasis, the 26-year-old
      patient with right upper abdominal pain for four weeks and laboratory findings
      suggesting an acute pancreatitis. The 22-year-old patient presented with painless
      jaundice. EUS-guided fine needle aspiration was performed in all patients. The
      cytological findings and the EUS were decisive for the diagnosis of autoimmune
      pancreatitis in all four cases. In contrast, no patient showed elevated IgG4, or
      antibodies for carboanhydrase-II, for lactoferrin, or rheumatoid factor, serum
      markers reported to be positive in autoimmune pancreatitis. All patients were
      treated successfully with steroids, one patient relapsed after discontinuing the
      steroid medication and required renewed therapy. These case reports demonstrate
      that autoimmune pancreatitis should be considered in the differential diagnosis
      in cases of pancreatitis and/or jaundice also in western countries. As
      demonstrated, the diagnosis should not be based solely on the elevation of IgG4
      or autoantibodies.

PMID- 18080227
TI  - Surgical treatment of gastrointestinal stromal tumor in the esophagus: report of
      three cases.
AB  - BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal
      tumors of the alimentary tract. The term GIST was introduced in 2004 and
      understanding of the tumor's cellular origin, classification, diagnostic markers,
      and prognostic parameters has evolved dramatically over the last two decades.
      Hirota et al. proposed that GISTs originate from interstitial cells of Cajal -
      regulators of gut peristalsis that normally express CD 117 - which is the product
      of the c-kit proto-oncogene that encodes a tyrosine kinase receptor that
      regulates cellular proliferation in GISTs. In the esophagus, squamous cell
      carcinoma and adenocarcinoma are common malignant tumors and leiomyoma is the
      most frequent mesenchymal neoplasm. Esophageal GISTs, however, have been reported
      less frequently. METHODS: We report three cases of esophageal GISTs in patients
      who underwent surgical intervention in our institution. The patients suffered
      from dysphagia, without specific findings on initial physical examination.
      Submucosal tumors were suspected after the patients underwent barium swallow and
      endoscopic studies. In addition, positron emission tomography was used to study a
      submucosal tumor in one patient. RESULTS: The pathological diagnosis was
      confirmed in all cases by microscopic examination with hematoxylin and eosin
      stain and positive immunoreaction for c-kit. Two of them were low risk and the
      third one was high risk in character, according to the consensus approach and
      depending on the size and mitotic index of the tumor. CONCLUSION: The patients
      had uneventful postoperative recoveries and were followed up regularly at 3-month
      intervals.

PMID- 18080228
TI  - [Eosinophilic esophagitis--pathogenesis, clinical presentation and therapeutic
      management].
AB  - Eosinophilic esophagitis (EE) is a relatively new, chronic, TH 2-type allergic
      inflammation of the esophagus. EE occurs more frequently in men. Allergic
      diseases such as asthma or atopic dermatitis are present in 50-70 % of patients
      or their relatives. In adults, the most common presenting symptom of EE is
      dysphagia, with or without food bolus impaction. Endoscopic findings of EE
      include mucosal furrows, corrugated or concentric rings or ridges in the
      esophagus ("feline esophagus"), with or without tiny whitish exudates. The
      diagnosis is confirmed by the observation of high counts of eosinophils in the
      esophageal epithelium (at least 24 /HPF). The cornerstones of medical therapy are
      either topical or systemic corticosteroids. Additional therapies included
      leukotriene receptor antagonists (montelukast) and IL-5 blockers (Mepolizumab).
      Complications of EE such as esophageal strictures should be carefully dilated
      using either bougies or a balloon. Currently it is still not known whether the
      late complications of EE can be prevented by the use of anti-inflammatory agents
      and this can only be demonstrated through further long-term follow-up studies.

PMID- 18080230
TI  - [Childhood achalasia: a separate entity?].
AB  - BACKGROUND: Achalasia in childhood is rare, also the etiology and the
      pathogenesis of the early onset ort he disease is practically unknown. Little is
      known about the neuropathological changes in structure of the esophageal wall in
      non-hereditary, sporadic achalasia in children and ist differentiation to that in
      adults. The aim of our study was to examine the morphological properties or high
      pressure zone of the lower esophageal sphincter in children who had undergone a
      Heller myotomy because of achalasia as well as to compare them with the
      pathological findings in adults. METHODS: Muscle biopsies of the smooth
      musculature, a 20 x 10 mm long segment of the myenteric of the distal esophagus
      (lower boundary of the esophageal incision of the myotomy), were taken for
      histopathological and immunohistochemical studies. RESULTS: A conspicuous
      histomorphological finding was a marked reduction of the myenteric ganglion
      through to complete aganglionosis of the high-pressure zone of the lower
      esophageal sphincter. In contrast to achalasia in adults, neural inflammation was
      found only rarely. A pronounced fibrosis of the smooth muscle layers was found in
      all patients whereas muscular hypertrophy or visceral myopathy was not present.
      The interstitial Cajal cells were reduced, similar to those in adults.
      CONCLUSIONS: The variability of the clinical and pathological properties in cases
      of childhood achalasia are indicative of a complex pattern of varying etiologies
      and a comparison with the disease in adults does not, in principle, allow the
      assumption of a separate clinical entity. The present findings are compatible
      with the histopathological results of hereditary achalasia in children as
      described for Allgrove's syndrome.

PMID- 18080229
TI  - [Barrett carcinoma--diagnosis, screening, surveillance, endoscopic treatment,
      prevention].
AB  - An adenocarcinoma of the distal esophagus may also be designated as Barrett's
      carcinoma as it evolves from Barrett's esophagus. Barrett's esophagus currently
      is defined as a columnar metaplasia of the distal esophagus, as identified by
      endoscopy, that, upon histopathology, is confirmed to contain intestinal
      metaplasia. A different histological entity of columnar metaplasia of the distal
      esophagus is cardia-type mucosa which probably precedes intestinal metaplasia,
      but lacks goblet cells typical for the latter. The conversion rate from Barrett's
      esophagus to Barrett's carcinoma amounts to 0.5 to 1 % per year. Patients with
      reflux symptoms should undergo early endoscopy in order to search for Barrett's
      esophagus (screening). In those cases where Barrett's esophagus is identified,
      regular endoscopic controls should be scheduled (surveillance). The intervals for
      this have been defined by recent consented guidelines. The aim is to detect
      neoplasia early. Neoplasia confined to the epithelium or mucosal layer can mostly
      be treated by endoscopic resection. The depth of infiltration, as determined by
      histopathology of the resected specimen, allows one to estimate the risk of lymph
      node metastasis, and therefore is crucial for the final judgment as to whether
      the endoscopic intervention may be considered curative. Individually, the risk of
      metastasis has to be weighed against the risk of morbidity and mortality
      conferred by the alternative surgical resection. The rapid increase of the
      incidence of Barrett's carcinoma in Western countries suggests that life style
      factors, in particular overweight, having a causal role. Data from interventional
      trials on prevention are, however, pending.

PMID- 18080231
TI  - Prophylaxis, diagnosis and therapy of hepatitis B virus (HBV) infection: the
      German guidelines for the management of HBV infection.

PMID- 18080232
TI  - [Intestinal microcirculation in abdominal sepsis].

PMID- 18080233
TI  - Piper cubeba targets multiple aspects of the androgen-signalling pathway. A
      potential phytotherapy against prostate cancer growth?
AB  - Despite the high prevalence of prostate cancer (PC) in the Western world, there
      is a dearth of effective medication. Since the androgen-signalling pathway is
      very much involved in PC growth and development, we investigated the potential of
      Piper cubeba L. extract, P9605, in targeting multiple events simultaneously
      within this pathway. This may be more effective compared to an antiandrogen
      monotherapy. Our results indicated that P9605 inhibited proliferation in androgen
      dependent LNCaP human prostate cancer cells by reducing DNA synthesis and
      inducing apoptosis. This antigrowth effect was less pronounced in androgen
      independent PC-3 prostate cancer cell lines. P9605 potently inhibited 5 alpha
      reductase II activity, which is responsible for converting testosterone to its
      active form, dihydrotestosterone (DHT), in the prostate. It also acted as an
      antagonist at recombinant wild-type androgen receptors (AR). P9605 suppressed
      cell growth and prostate-specific antigen (PSA) secretion stimulated by
      physiological concentrations of DHT in LNCaP cells. Interestingly, it down
      regulated AR levels. In conclusion, our findings suggest that P9605 may
      potentially retard the growth of androgen-dependent PC via several mechanisms.

PMID- 18080234
TI  - Novel ent-Beyeran-19-oic acids from biotransformations of isosteviol metabolites
      by Mortierella isabellina.
AB  - Biotransformations of ENT-16beta-hydroxybeyeran-19-oic acid ( 1) by Mortierella
      isabellina produced hydroxylated metabolites. The isolated metabolites included
      three new compounds, ent-14beta,16beta-dihydroxybeyeran-19-oic acid ( 3), ent
      12beta-hydroxy-16-oxobeyeran-19-oic acid ( 4), and ent-7alpha,12beta-dihydroxy-16
      oxobeyeran-19-oic acid ( 5), and one known compound, ent-7alpha,16beta
      dihydroxybeyeran-19-oic acid ( 2). The structural elucidation was achieved by
      detailed analysis of LC-MS chromatograms, and MS and NMR spectroscopic data. In
      this study, M. isabellina hydroxylated the basic skeleton beyeran-19-oic acid at
      the 7beta-, 12alpha-, and 14alpha-positions, and oxidized the skeleton at the 16
      position. All compounds were evaluated with the cell viability assay. The results
      of the bioassay indicated that MTT formazan exocytosis occurs upon treatment of
      the cells with 1.

PMID- 18080235
TI  - [Landmarks of physiological development of the voice in childhood and adolescense
      (Part 1)].
AB  - The area of the functioning of the voice is a fundamental element of human
      communication apart from language, speaking, hearing and perceiving. Detailed
      knowledge of normal vocal development is a prerequisite for the diagnosis and
      therapy of vocal dysfunctions among children and adolescents by means of methods
      suitable for their age and their stages of development. In an overview, the
      landmarks of physiological development with normal value ranges relevant to
      practice are presented--from the newborn baby's first cry up to the age of young
      adults. The effects of various degrees of vocal activity on the part of children
      and adolescents on the parameters of vocal capacity and quality are taken into
      account, as well as the relationship between physical and vocal development.
      Furthermore, an overview of diagnostic methods suitable for this age group is
      given. Specialists for ENT and for Phoniatrics and Pediatric Audiology should be
      able to assess suitability for increased vocal activity and to care for vocal
      development during the vulnerable phase of the voice change. Manifold socio
      cultural and pedagogical influences are already possible in early childhood and
      throughout the phase of the "voice in growth". They should be taken advantage of
      prophylactically--also with regard to the learning of physiological vocal
      behavior as a prerequisite for dealing with possible subsequent strain in vocally
      intensive professions. In the following second part of this publication, the
      fundamentals described here are applied to diagnostics and therapy of vocal
      dysfunctions in this age group by means of methods suitable for this stage of
      development.

PMID- 18080237
TI  - [From the expert's office: bilateral high-frequency hearing loss with C5-Senke
      following explosion].

PMID- 18080238
TI  - [Antiseptics for ENT diseases].
AB  - Studies of the use of antiseptics for the treatment of diseases of the ear, nose
      and throat are rather rare in literature. Many of the until recently common drugs
      are now assessed as obsolete or dispensable. The local application of systemic
      antibiotics has to be rejected because of the microbial development of antibiotic
      resistance. Here is where antiseptics prove to have maintained their importance.
      On the basis of the present literature, an overview is given of the antiseptics
      that are presently recommended for use in ENT practice and their use in the area
      of the oral cavity, the nose, the ear and in wounds.

PMID- 18080239
TI  - Isolation and characterization of process related impurities of olanzapine using
      HPLC and ESI-MS/MS.
AB  - An RP-HPLC method for the simultaneous separation and determination of olanzapine
      (OLZ) and its process impurities in bulk drugs and pharmaceutical formulations
      was developed. The separation was accomplished on Inertsil ODS 3V (4.6 mm x 250
      mm; particle size 5 microm) column using 0.2 M ammonium acetate (pH = 4.50) and
      ACN as mobile phase in gradient elution mode. The analytes were monitored by a
      photo diode array (PDA) detector set at 254 nm and the flow rate was kept at 1.0
      mL/min. The chromatographic behavior of all the compounds was examined under
      variable compositions of different solvents, buffer concentrations, and pH. The
      method was validated in terms of accuracy, precision, and linearity. Four unknown
      process impurities observed consistently during the analysis of different batches
      of OLZ were isolated and characterized by ESI-MS/MS, (1)H NMR, and FT-IR. The
      proposed RP-HPLC method was successfully applied to the analysis of commercial
      formulations. The method could be of use not only for rapid and routine
      evaluation of the quality of OLZ in bulk drug manufacturing units but also for
      the detection of its impurities in pharmaceutical formulations.

PMID- 18080240
TI  - Correlations of dietary patterns with prostate health.
AB  - Both genetic and environmental influences may be involved in etiology of prostate
      health and prostate cancer. These include ethnic origin, family history, smoking,
      and diet. Adiposity and excess energy intake are potentially distinct risk
      factors and positive associations with prostate cancer risk for both were
      observed among case-control and cohort studies. Some epidemiological studies
      support an association between dietary fat, particularly saturated or animal
      fats, and prostate cancer risk. Of these, several suggest reduced risk with low
      fat diets high in n-3 fatty acids and increased risk with high-fat diets rich in
      n-6 fatty acids. Others suggested association with higher meat intake, possibly
      due to heterocyclic amines and polycyclic aromatic hydrocarbons, produced during
      grilling or frying. Positive association of prostate cancer risk with dairy
      intake could involve alpha-methylacyl-CoA racemase activity (required for beta
      oxidation of phytanic acid present in dairy products and red meat) or the
      suppression of vitamin D activity by calcium. Inverse associations were observed
      with dietary intake of plant foods. These include cereals, soy products, and
      fruit and vegetable sources of carotenoids. Numerous plant constituents may act
      synergistically in the prevention and inhibition of prostate disorders. These
      diet-risk associations may lead to future individualized diet recommendations
      based upon genetic polymorphisms.

PMID- 18080241
TI  - Nutrition and hemostasis: a focus on urbanization in South Africa.
AB  - South Africa is experiencing a rapid urbanization of its African population
      characterized by a demographic, nutrition, lifestyle, and health transition. The
      resultant high prevalence of high cardiovascular disease, in particular of
      stroke, is of concern. In this narrative review it is suggested that, together
      with hypertension, changes in the hemostatic system may be one of the major
      contributors to stroke in this population. It is further suggested that these
      changes are related to increased fat and animal protein intakes, decreased
      intakes of total carbohydrate and dietary fiber, as well as persistent suboptimal
      micronutrient intakes of Africans in transition. The effects of this nutrition
      transition on plasma fibrinogen, fibrin network structures, plasminogen activator
      inhibitor 1 activity levels and some other clotting and fibrinolytic factors are
      discussed. It is concluded that despite indications of present protective
      mechanisms against the development of coronary heart disease (CHD) in this
      population the observed changes in diet and hemostatic profiles may eventually
      lead to a high prevalence of both stroke and CHD in urban black South Africans.
      It is further suggested that timely nutritional interventions and research of
      effects thereof on the hemostatic system are urgently needed.

PMID- 18080242
TI  - Food bioactives, apoptosis, and cancer.
AB  - Apoptosis interchangeably referred to as programmed cell death is a key pathway
      for regulating homeostasis and morphogenesis of mammalian cells and is connected
      with several diseases, in particular, cancer. It is widely believed that
      misregulation of this pathway leads to the development of cancer. Reflecting this
      knowledge, the mechanism of action for many currently used anticancer agents were
      specifically targeted to regulate the apoptotic pathway further stressing the
      role of programmed cell death in maintaining normal homeostasis. Another widely
      accepted concept is the consumption of a variety of colorful foods with strong
      antioxidant properties. These dietary components also referred to as bioactives
      would help maintain a healthy body. Although for many of these bioactives exact
      nutritional benefits are not yet well defined, there is demonstrated scientific
      evidence suggesting a role for them in cancer prevention. This review summarizes
      the current knowledge of food bioactives that act through the signaling pathway
      inducing programmed cell death, thus providing the evidence for these substances
      in cancer prevention.

PMID- 18080243
TI  - Application of electron spin resonance (ESR) spectrometry in nutraceutical and
      food research.
AB  - Electron spin resonance (ESR) spectroscopy is able to directly measure the
      chemical species with unpaired electrons and has been widely used in a number of
      research fields. This review focused on its application in nutraceutical and food
      research. Current status of ESR in free radical scavenging capacity estimation,
      food oxidative stability evaluation, Cu(2+) chelating capacity determination were
      summarized. Also discussed was the potential of ESR spin-label oximetry technique
      in examination of lipid peroxidation and oxygen diffusion-concentration products
      in liposomes, oxygen transport and depletion, and membrane structure and dynamic
      properties. In addition, ESR application in identifying and estimating irradiated
      foods including meat, fruits, vegetables, spices, cereal grains, and oil seeds
      was reviewed. Finally, the potential use of ESR technique in investigating
      microstructure change, phase transition and viscosity related properties during
      food formulation, processing, and storage was briefly mentioned, along with its
      potential in determination of radio-stability of food components. This review may
      provide some fundamental knowledge of ESR and its application in nutraceutical
      and food research.

PMID- 18080244
TI  - Chemical stability of haloperidol injection by high performance thin-layer
      chromatography.
AB  - The chemical stability of haloperidol lactate injection was studied under
      different storage conditions by high performance thin-layer chromatography
      (HPTLC). The study was performed at 25 +/- 2 degrees C and at refrigeration
      temperature (8 +/- 1 degrees C) in original glass ampoules over 15 days after
      being opened. The samples tested at 25 +/- 2 degrees C were stored with exposure
      to and protection from light. Chromatographic separation was achieved on
      precoated silica gel F 254 HPTLC plates using a mixture of acetone/chloroform/n
      butanol/glacial acetic acid/water (5:10:10:2.5:2.5, v/v/v/v/v) as a mobile phase.
      Quantitative analyses were carried out at a wavelength of 254 nm. The method
      exhibited adequate linearity (r = 0.999), selectivity, precision (RSD = 1.92%),
      and accuracy (recoveries from 98.59 to 101.90%). The concentrations of all
      samples remained greater than or 90% of the original concentration. Haloperidol
      lactate injection was chemically stable under all conditions studied over 15
      days.

PMID- 18080245
TI  - Temperature sensitivity and fluorescence detection.
AB  - Fluorescence detectors are about three orders of magnitude more sensitive and
      specific making them ideal for trace analysis and complex sample matrices.
      However, temperature dependence of the signal is a disadvantage to fluorescence
      detectors. We have previously reported degradation of malondialdehyde (MDA)
      thiobarbituric acid (TBA) adduct at room temperature. The present experiments
      tested the notion that the detector response may be blunted due to increase in
      temperature over time. Repeated injections of the same standard curve over 4 h
      found a significant effect of time on the slopes of peak area-concentration
      curves. When the samples were iced and injected alternating with ambient
      temperature standard curve samples, no differences in slopes were seen between
      iced and ambient temperature samples. Cooling the housing of the fluorescence
      lamp significantly increased the fluorescence in the samples. Fluorescence
      increased 2.5% (95% confidence interval, 1.5-3.6%) for each 1 degrees C fall in
      temperature. MDA-TBA adduct remained stable at room temperature. Since the
      fluorescence signal is temperature sensitive, letting the detector warm up for 2
      h to obtain a steady temperature is more likely to give reproducible results
      compared to a detector that has not warmed up. These results have implications
      for other applications utilizing fluorescence detectors.

PMID- 18080246
TI  - Thiosugars--derivatization agents for chiral resolution of homoleucines.
AB  - o-Phthaldialdehyde was used in combination with a series of six thiosugars for
      the pre-column chiral derivatization of selected primary amino acids. The
      diastereomers were resolved on a conventional reversed-phase column and with
      fluorescence detection. A surprisingly effective resolution of 1-isoindolyl-(1
      thioglycosides) derived from 1-thio-beta-L-fucose was observed.

PMID- 18080247
TI  - On-line concentration of proteins by SDS-CGE with LIF detection.
AB  - We present a simple approach for on-line concentration of SDS-protein complexes
      by using poly(vinyl alcohol) (PVA) solution in CGE. In comparison to the coated
      capillary, the presence of EOF in CGE omitted the need to fill the capillaries
      with polymer solutions prior to the analysis. More importantly, we found that
      highly reproducible separation of eight proteins by 3.5% PVA was achieved between
      runs and without the regeneration of high bulk EOF; the RSD of migration times
      was less than 0.7%. To further improve the concentration sensitivity, neutral PVA
      was introduced into the capillary with the help of EOF to act as sieving matrix.
      The occurrence of stacking at the boundary between the PVA and the sample zone is
      mainly due to the retardation of proteins by PVA. As a result, the LODs at an S/N
      of 3 for SDS-protein complexes are of the order of sub-nM to several nM. For
      example, the LOD for BSA is 0.78 nM, which is a 91-fold sensitivity enhancement
      over the normal injection. In addition, our stacking method has been applied to
      the analyses of proteins in Escherichia coli cells. The peak for beta
      galactosidase (E. coli) was observed after 0.1 microM beta-galactosidase was
      spiked into the E. coli samples.

PMID- 18080248
TI  - CE hydrogen deuterium exchange-MS in peptide analysis.
AB  - CE and hydrogen-deuterium (H/D) exchange MS are useful tools in the analysis and
      characterisation of peptides. This study reports the facile coupling of these
      tools in the H/D exchange CE-MS analysis of model and pharmaceutically important
      peptides, using a sheath flow interface. The peptides varied in mass from 556
      (leucine enkephalin) to 1620 Da (bombesin), and in charge state from 0.33
      (leucine enkephalin) to 3.0 (substance P). The application of a BGE composed of
      ammonium formate buffer (25 mM, pD 3.5 in D(2)O (>98% D atom)), a sheath liquid
      composed of formic acid (0.25% v/v in D(2)O) and ACN (30:70 v/v), and dissolving
      the samples in a mixture of ACN/D(2)O (50:50 v/v) facilitates complete H/D
      exchange. Because of complete H/D exchange the ESI mass spectra produced are easy
      to interpret and comparable to those obtained from LC-MS analysis. The CE-H/D-MS
      approach has the advantage of requiring lower volumes of deuterated solvents. The
      b- and y-series fragments produced by using in-source decomposition correspond to
      those predicted. With the peptides studied, the complete exchange H/D exchange
      observed with both the molecular and fragment ions helps to confirm both amino
      acid composition and sequence.

PMID- 18080249
TI  - Two-color electrophoretic immunoassay for simultaneous measurement of insulin and
      glucagon content in islets of Langerhans.
AB  - A multianalyte CE competitive immunoassay using two-color detection was developed
      to measure insulin and glucagon in islets of Langerhans. Insulin was quantified
      with FITC-insulin (Ins*) and anti-insulin antibodies (Ins Ab) and glucagon was
      quantified with Cy5-glucagon (Glu*) and anti-glucagon antibodies (Glu Ab). A 3 mW
      Ar(+) laser at 488 nm and a 25 mW laser diode at 635 nm were used to excite FITC
      and Cy5, respectively. Fluorescence was split with a half-silvered mirror and
      passed through a 520 +/- 20 nm bandpass filter or a 663 nm longpass filter for
      the detection of insulin and glucagon, respectively. The two-color detection
      format enabled independent quantitation of both analytes even with concentrations
      of insulin immunoassay reagents 20-fold higher than glucagon reagents.
      Simultaneous calibration curves were generated and used to determine insulin and
      glucagon content in islets of Langerhans. Amounts of insulin and glucagon were
      56.6 +/- 3.2 and 1.0 +/- 0.5 ng/islet, respectively. LODs were 7 nM insulin and 3
      nM glucagon. The assay will be applicable to fast monitoring of multiple peptides
      secreted from islets of Langerhans and can be applied to other systems for the
      quantitation of multiple analytes with large differences in concentrations.

PMID- 18080250
TI  - Determination of sulfophenyl carboxylic acids in agricultural groundwater samples
      by CE with ultraviolet absorption detection.
AB  - An analytical method for the determination of six sulfophenyl carboxylic acids,
      namely (p-sulfophenyl)acetic, 2-(p-sulfophenyl)propionic, 2-(p
      sulfophenyl)butyric, 3-(p-sulfophenyl)butyric, 4-(p-sulfophenyl)butyric, and 5-(p
      sulfophenyl)valerianic acid, in agricultural irrigation water samples was
      developed. It involves an SPE procedure, an on-line preconcentration normal
      stacking mode and subsequent separation and determination using CE with UV
      detection (CE-UV). p-Sulfobenzoic acid was used as internal standard. The
      compounds were separated with an uncoated capillary and a 25 mM ammonium
      acetate/acetic acid buffer solution (pH 5.5) with 2-propanol (30% v/v) and 0.75
      mM CTAB. Analyses were run at -25 kV, 25 degrees C, and 100 s of hydrodynamic
      injection with UV detection at 225 nm. Quantification limits found ranged between
      4 and 6 ng/mL. The proposed method was validated using a recovery assay. It was
      satisfactorily used for the determination of these compounds in groundwater
      samples to track down the biodegradation of linear alkylbenzene sulfonates in an
      agricultural soil from the fertile plain of Granada (Spain).

PMID- 18080251
TI  - CE combined with rolling circle amplification for sensitive DNA detection.
AB  - Here we describe an assay which combines CE with rolling circle amplification
      (RCA) for sensitive DNA detection and quantification. RCA is an isothermal DNA
      replication technique that generates a long ssDNA with tandem repeats. It
      requires simpler temperature control in reaction and offers higher sequence
      specificity and greater quantitation capability compared to other amplification
      technologies. In this study, RCA amplified the DNA target via a circular
      template, and the product was digested into monomers for CE analysis. Less than 2
      fmol of the DNA target could easily be detected using this RCA-CE assay and the
      assay has a dynamic range of two orders of magnitudes. Moreover, simultaneous
      detection of both the target DNA and the internal standard was achieved by
      designing two padlock probes with different sizes, which could significantly
      improve the quantification accuracy. The RCA-CE assay is easy to perform, readily
      adaptable for detection of multiple targets because of the high resolution power
      of CE, and is compatible with other applications employing RCA as a signal
      amplification tool. Additionally, this assay can be used with a capillary array
      system to perform sensitive, high-throughput genetic screening.

PMID- 18080252
TI  - CE of poly(amidoamine) succinamic acid dendrimers using a poly(vinyl alcohol)
      coated capillary.
AB  - Various generations (G1-G8) of negatively charged poly(amidoamine) (PAMAM)
      succinamic acid dendrimers (PAMAM-SAH) were analyzed by CE using a poly(vinyl
      alcohol)-coated capillary. Due to its excellent stability and osmotic flow
      shielding effect, highly reproducible migration times were achieved for all
      generations of dendrimer (e.g., RSD for the migration times of G5 dendrimer was
      0.6%). We also observed a reverse trend in migration times for the PAMAM-SAH
      dendrimers (i.e., higher generations migrated faster than lower generation
      dendrimers) compared to amine-terminated PAMAM dendrimers reported in the
      literature. This reversal in migration times was attributed to the difference in
      counterion binding around these negatively charged dendrimers. This reverse trend
      allowed a generational separation for lower generation (G1-G3) dendrimers.
      However, a sufficient resolution for the migration peaks of higher generations
      (G4-G5) in a mixture could not be achieved. This could be due to their nearly
      identical charge/mass ratio and dense molecular conformations. In addition, we
      show that dye-functionalized PAMAM-SAH dendrimers can also be analyzed with high
      reproducibility using this method.

PMID- 18080253
TI  - The effect of conditioning of fused-silica capillaries on their electrophoretic
      performance.
AB  - In CE practice, conditioning of the capillary tube with strong base, acid, or
      both in sequence, has been recognized as essential to obtain reasonable precision
      in electroosmotic mobility (EOM), and consequently, in the migration times of
      analytes. This report focuses on the comparative study of three different
      approaches for capillary conditioning: etching with HF, etching with NaOH, and
      leaching with HCl after NaOH treatment. EOM-based measurements, including the
      hysteresis effect that characterizes the dependence of EOM with pH, were used to
      evaluate the conditioned silica surface. Additionally, indirect inspection of the
      conditioned surface was carried out by examining the electrophoretic profile of
      the cationic probe Ru(bpy)(3) (2+), known to strongly interact with the ionized
      silica surface while displaying no significant acid-base activity. It was shown
      that, once conditioned and prior to any CE measurement, extensive rinse of the
      capillary with the running electrolyte at high flow rate was essential to attain
      relatively rapid re-equilibration of the tube with the fluid. Insufficient rinse
      with the running electrolyte would result in negatively biased EOM measurements
      and significant drift in migration times. It was also established that relatively
      high flow rates of 1 M NaOH conditioning solution (4-5 column volumes per minute)
      was required to attain capillaries with reproducible electrophoretic performance
      within a reasonable conditioning time (typically, 1 h). In addition to relatively
      more extensive rehydroxylation of the silica surface, evidenced by the highest
      EOM values obtained, the sequential use of NaOH-etching and HCl-leaching provided
      better precision than HF-etching or NaOH-etching alone.

PMID- 18080254
TI  - A multiplex assay to identify 18 European mammal species from mixtures using the
      mitochondrial cytochrome b gene.
AB  - A novel species-specific multiplex to identify 18 common European mammalian
      species (badger, cat, cow, dog, donkey, fox, goat, guinea pig, harvest mouse,
      hedgehog, horse, house mouse, human, pig, rabbit, rat, red deer and sheep), many
      of which are often associated with forensic investigations, has been developed.
      The assay is based on the mitochondrial cytochrome b gene, which is commonly used
      in species identification and phylogeny studies. Areas of homology and variation
      were identified and were used to create universal and species-specific primers.
      The species-specific primers were designed such that they will only react with
      the species for which they were designed. Two primer sets were designed for each
      species making the test self-confirmatory. All primer sets produced the expected
      results. The multiplex was balanced at template concentration of 40 000 copies
      (approximately 1.36 pg). Validation was accomplished by analysing the same sample
      ten times to determine run variation and several samples for each species to
      determine between-sample variation. Twenty-eight additional mammalian species
      were reacted with the multiplex. The multiplex provides, for the first time, a
      definitive method for identification of species in a forensic context.

PMID- 18080255
TI  - Oxidative cross-coupling of arenes induced by single-electron transfer leading to
      biaryls by use of organoiodine(III) oxidants.

PMID- 18080256
TI  - Self-assembling nanoparticles at surfaces and interfaces.
AB  - Nanoparticles are the focus of much attention due to their astonishing properties
      and numerous possibilities for applications in nanotechnology. For realising
      versatile functions, assembly of nanoparticles in regular patterns on surfaces
      and at interfaces is required. Assembling nanoparticles generates new
      nanostructures, which have unforeseen collective, intrinsic physical properties.
      These properties can be exploited for multipurpose applications in
      nanoelectronics, spintronics, sensors, etc. This review surveys different
      techniques, currently employed and being developed, for assembling nanoparticles
      in to ordered nanostructures. In this endeavour, the principles and methods
      involved in the development of assemblies are discussed. Subsequently, different
      possibilities of nanoparticle-based nanostructures, obtained in multi-dimensions,
      are presented.

PMID- 18080257
TI  - Transmission holographic polymer dispersed liquid crystals based on a siloxane
      polymer.
AB  - The low surface energy and the great immiscibility of poly (dimethylsiloxane)
      (PDMS) with liquid crystals (LCs) are used in the fabrication of holographic
      polymer dispersed liquid crystals (HPDLCs). By adding increasing amounts of PDMS,
      the extent of the phase separation between the polymer and the LC, the LC channel
      width, and-eventually-also the diffraction efficiency of the film can be
      increased, while keeping the droplet size essentially the same. In addition, the
      presence of PDMS causes a decrease in the switching voltage and an increase in
      the response time. At an optimum content of PDMS (PUA40), a minimum switching
      voltage of 4 V microm(-1), a rise time of 0.20 ms, and a decay of 14.75 ms were
      obtained. Regarding the effect of the LC content, an overshoot of the diffraction
      efficiency was observed when the amount of LC exceeded 35 %, which can be
      attributed to droplet coalescence.

PMID- 18080258
TI  - Visualizing the frontier orbitals of a conformationally adapted metalloporphyrin.
AB  - We present a molecular-level study of the geometric and electronic properties of
      Co(II) tetraphenylporphyrin molecules adsorbed on the Cu(111) surface. A
      combination of low-temperature scanning tunneling microscopy and near-edge X-ray
      absorption fine structure observations reveals how the metal substrate induces a
      conformational adaptation into a distorted saddle-shaped geometry. By scanning
      tunneling spectroscopy we identified the discrete energy levels of the molecule
      and mapped their spatial electron-density distributions. These results, along
      with a simple theoretical description, provide a direct correlation between the
      shape of frontier molecular orbitals and intramolecular structural features.

PMID- 18080260
TI  - Organocatalytic enantioselective one-pot synthesis and application of substituted
      1,4-dihydropyridines--Hhantzsch ester analogues.
AB  - An easy and simple one-pot approach for the formation of optically active
      substituted 1,4-dihydropyridines by using asymmetric organocatalysis is
      presented. The one-pot reaction of alpha,beta-unsaturated aldehydes with beta
      diketones or beta-ketoesters and primary amines gives optically active 2,3
      substituted 1,4-dihydropyridines in moderate yields and with enantioselectivities
      up to 95 % ee. It is also demonstrated that the optically active 1,4
      dihydropyridines can be used in situ for the direct enantioselective reduction
      of, for example, alpha-ketoesters with high enantioselectivity.

PMID- 18080259
TI  - Monodisperse magnetite nanoparticles coupled with nuclear localization signal
      peptide for cell-nucleus targeting.
AB  - Functionalization of monodisperse superparamagnetic magnetite (Fe(3)O(4))
      nanoparticles for cell specific targeting is crucial for cancer diagnostics and
      therapeutics. Targeted magnetic nanoparticles can be used to enhance the tissue
      contrast in magnetic resonance imaging (MRI), to improve the efficiency in
      anticancer drug delivery, and to eliminate tumor cells by magnetic fluid
      hyperthermia. Herein we report the nucleus-targeting Fe(3)O(4) nanoparticles
      functionalized with protein and nuclear localization signal (NLS) peptide. These
      NLS-coated nanoparticles were introduced into the HeLa cell cytoplasm and
      nucleus, where the particles were monodispersed and non-aggregated. The success
      of labeling was examined and identified by fluorescence microscopy and MRI. The
      work demonstrates that monodisperse magnetic nanoparticles can be readily
      functionalized and stabilized for potential diagnostic and therapeutic
      applications.

PMID- 18080261
TI  - Conformational preference and potential templates of N-methylated cyclic
      pentaalanine peptides.
AB  - Systematic N-methylation of all peptide bonds in the cyclic pentapeptide cyclo(-D
      Ala-Ala(4)-) has been performed yielding 30 different N-methylated derivatives,
      of which only seven displayed a single conformation on the NMR time scale. The
      conformation of these differentially N-methylated peptides was recently reported
      by us (J. Am. Chem. Soc. 2006, 128, 15 164-15 172). Here we present the
      conformational characterization of nine additional N-methylated peptides from the
      previous library which are not homogeneous but exist as a mixture in which at
      least one conformation is preferred by over 80 %. The structures of these
      peptides are investigated employing various 2D-NMR techniques, distance geometry
      calculations and further refined by molecular dynamics simulations in explicit
      DMSO. The comparison of the conformation of these nine peptides and the seven
      conformationally homogeneous peptides allow us to draw conclusions regarding the
      influence of N-methylation on the peptide backbone of cyclic pentapeptide of the
      class cyclo(-D-Ala-Ala(4)-). Here we present the different conformational classes
      of the peptides arising from the definitive pattern of N-methylation which can
      eventually serve as templates for the design of bioactive peptides.

PMID- 18080262
TI  - Highly Enantio- and s-trans C=C bond selective catalytic hydrogenation of cyclic
      enones: alternative synthesis of (-)-menthol.
AB  - A highly enantioselective catalytic hydrogenation of cyclic enones was achieved
      by using the combination of a cationic Rh(I) complex, (S)-5,5'-bis{di(3,5-di-tert
      butyl-4-methoxyphenylphosphino)}-4,4'-bi-1,3-benzodioxole (DTBM-SEGPHOS), and
      (CH2CH2PPh3Br)2. The presence of an s-cis C=C bond isopropylidene moiety on the
      cyclic enone influenced the enantioselectivity of the hydrogenation. Thus, the
      hydrogenation of 3-alkyl-6-isopropylidene-2-cyclohexen-1-one, which contains both
      s-cis and s-trans enones, proceeded in excellent enantioselectivity (up to 98 %
      ee). To obtain high enantio- and s-trans selectivities, the addition of a halogen
      source to the cationic Rh complex was the essential step. With the key step of
      the s-trans selective asymmetric hydrogenation of piperitenone, we demonstrated a
      new synthetic method for optically pure (-)-menthol via three atom-economical
      hydrogenations. Moreover, we found that the complete s-trans and s-cis C=C bond
      selective reactions were also realized by the proper choice of both the chiral
      ligands and halides.

PMID- 18080263
TI  - Synthesis, molecular structure and properties of the [H6-nNi30C4(CO)34(CdCl)2]n-
      (n=3-6) bimetallic carbide carbonyl cluster: a model for the growth of noncompact
      interstitial metal carbides.
AB  - Reaction of the [Ni(9)C(CO)(17)](2-) dianion with CdCl(2)2.5 H(2)O in THF affords
      the novel bimetallic Ni--Cd carbide carbonyl clusters [H(6
      n)Ni(30)C(4)(CO)(34)(micro(5)-CdCl)(2)](n-) (n=3-6), which undergo several
      protonation-deprotonation equilibria in solution depending on the basicity of the
      solvent or upon addition of acids or bases. Although the occurrence in solution
      of these equilibria complicates the pertinent electrochemical studies on their
      electron-transfer activity, they clearly indicate that the clusters [H(6
      n)Ni(30)C(4)(CO)(34)(micro(5)-CdCl)(2)](n-) (n=3-6), as well as the structurally
      related [H(6-n)Ni(34)C(4)(CO)(38)](n-) (n=4-6), undergo reversible or partially
      reversible redox processes and provide circumstantial and unambiguous evidence
      for the presence of hydrides for n=3, 4 and 5. Three of the [H(6
      n)Ni(30)C(4)(CO)(34)(micro(5)-CdCl)(2)](n-) anions (n=4-6) have been structurally
      characterized in their [NMe(3)(CH(2)Ph)](4)[H(2)Ni(30)C(4)(CO)(34)(CdCl)(2)]2
      COMe(2), [NEt(4)](5)[HNi(30)C(4)(CO)(34)(CdCl)(2)]2 MeCN and
      [NMe(4)](6)[Ni(30)C(4)(CO)(34)(CdCl)(2)]6 MeCN salts, respectively. All three
      anions display almost identical geometries and bonding parameters, probably
      because charge effects are minimized by delocalization over such a large metal
      carbonyl anion. Moreover, the Ni(30)C(4) core in these Ni-Cd carbide clusters is
      identical within experimental error to those present in the
      [HNi(34)C(4)(CO)(38)](5-) and [Ni(35)C(4)(CO)(39)](6-) species, suggesting that
      the stepwise assembly of their nickel carbide cores may represent a general
      pathway of growth of nickel polycarbide clusters. The fact that the [H(6
      n)Ni(30)C(4)(CO)(34)(micro(5)-CdCl)(2)](n-)(n=4-6) anions display two valence
      electrons more than the structurally related [H(6-n)Ni(34)C(4)(CO)(38)](n-) (n=4
      6) species has been rationalized by extended Huckel molecular orbital (EHMO)
      analysis.

PMID- 18080264
TI  - Pd PEPPSI-IPr-mediated reactions in metal-coated capillaries under MACOS: the
      synthesis of indoles by sequential aryl amination/Heck coupling.
AB  - A method has been devised for the microwave-assisted, continuous-flow preparation
      of indole alkaloids by a two-step aryl amination/cross-coupling sequence of
      bromoalkenes and 2-bromoanilines. This process requires both the presence of a
      metal-lined flow tube (a 1180 micron capillary) and the Pd PEPPSI-IPr catalyst;
      without either, the catalyst or the film, there is zero turnover of this
      catalytic process. A silver film has been shown to provide some conversion (48-62
      %), but optimal results (quantitative) across a variety of bromoalkenes and
      bromoanilines were achieved by using a highly porous palladium film. Possible
      roles for the Pd film are considered, as is the interplay of the catalyst and the
      film.

PMID- 18080265
TI  - Concerted proton-electron transfer in pyridylphenols: the importance of the
      hydrogen bond.

PMID- 18080267
TI  - New routes for the functionalization of P4.

PMID- 18080266
TI  - Cationic rare-earth-metal half-sandwich complexes for the living trans-1,4
      isoprene polymerization.

PMID- 18080268
TI  - Crystal-to-crystal transformation between three Cu(I) coordination polymers and
      structural evidence for luminescence thermochromism.

PMID- 18080270
TI  - Successful management of a Jehovah's Witness with thrombotic thrombocytopenic
      purpura unwilling to be treated with therapeutic plasma exchange.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease treated
      successfully with plasma exchange. Jehovah's Witnesses whose religious beliefs
      preclude them from accepting plasma exchange may require alternative forms of
      therapy. We report a case of one such patient who presented with TTP, whom we
      successfully managed with vincristine and responded favorably without the need
      for plasma exchange.

PMID- 18080271
TI  - Therapeutic plasma exchange performed in parallel with extra corporeal membrane
      oxygenation for antibody mediated rejection after heart transplantation.
AB  - We report on the feasibility, safety, and efficacy of performing therapeutic
      plasmapheresis (TPE) in parallel with extracorporeal membrane oxygenation (ECMO)
      to alleviate antibody mediated rejection (AMR) after heart transplantation. Two
      pediatric and one adult patient presented with severe congestive heart failure
      and respiratory distress after heart transplantation and required ECMO support.
      TPE was initiated to treat AMR while patients remained on ECMO. Each patient
      received three to five procedures either every day or every other day. One
      equivalent total plasma volume (TPV) was processed for each procedure (patient
      TPV + ECMO extracorporeal TPV). A total of 13 TPE procedures were performed with
      12 procedures completed without complications or adverse events; one procedure
      was terminated before completion because of cardiac arrhythmia. Anti-HLA antibody
      titers decreased after TPE in all three patients. Ventricular function improved
      and ECMO was discontinued in 2 of 3 patients. Performing large volume TPE with a
      processed volume up to 2.5 times the patient's TPV is well tolerated in both
      pediatric (< or = 10 kg) and adult patients. TPE in parallel with ECMO is
      feasible, safe, and may be measurably effective at reducing anti-HLA antibodies
      and should be considered as part of the treatment for patients with early AMR
      after heart transplantation.

PMID- 18080272
TI  - Performance of a new separator system for routine autologous hematopoietic
      progenitor cell collection in small children.
AB  - The AMICUS system was recently introduced for peripheral blood stem cell (PBSC)
      aphereses in adults. We conducted a single center field evaluation to obtain data
      about the performance of this system in children with a body weight (bw) < 25 kg.
      Results of blood priming procedures were compared to historical data obtained
      with the Fenwal CS3000+ (CS 3000). From August, 2001 to February, 2007, 47/178
      (26%) PBSC aphereses procedures were performed in our institution with the AMICUS
      system in 35 small patients (median bw 13.9 kg; range 6.7-24; age 2.78 years;
      range 0.97-7.06). The patients suffered from various malignant primary diseases
      or recurrences. We primed the system with packed RBC in case of >30% dilution of
      the RBC volume (n = 31) or with saline (n = 16). Compared to the CS3000, the
      AMICUS revealed comparable collection efficiencies (CE) for CD34+ cells (median
      67%, range 26-120), lymphocytes (75%, 25-138), monocytes (54%, 23-173), and
      granulocytes (10%, 1.5-36), MNC (57% 24-125), but a significantly higher
      erythrocyte and granulocyte, and a lower platelet CE. There was a significant
      negative correlation between total leukocyte count and CE for MNC (r = -0.566; P
      < 0.001) and CD34+ cells (r = -0.517; P < 0.001). There was no significant
      statistical or clinical difference between the CE in blood-primed procedures and
      saline-primed procedures. With the AMICUS we saw statistically less citrate
      reactions compared to the CS 3000. We conclude that the AMICUS system is safe and
      efficient to harvest PBSC on a routine basis in pediatric patients, even in
      children < or =10 kg bw.

PMID- 18080276
TI  - Towards the optimal screening collection: a synthesis strategy.
AB  - The development of effective small-molecule probes and drugs entails at least
      three stages: 1) a discovery phase, often requiring the synthesis and screening
      of candidate compounds, 2) an optimization phase, requiring the synthesis and
      analysis of structural variants, 3) and a manufacturing phase, requiring the
      efficient, large-scale synthesis of the optimized probe or drug. Specialized
      project groups tend to undertake the individual activities without prior
      coordination; for example, contracted (outsourced) chemists may perform the first
      activity while in-house medicinal and process chemists perform the second and
      third development stages, respectively. The coordinated planning of these
      activities in advance of the first small-molecule screen tends not to be
      undertaken, and each project group can encounter a bottleneck that could, in
      principle, have been avoided with advance planning. Therefore, a challenge for
      synthetic chemistry is to develop a new kind of chemistry that yields a screening
      collection comprising small molecules that increase the probability of success in
      all three phases. Although this transformative chemistry remains elusive,
      progress is being made. Herein, we review a newly emerging strategy in diversity
      oriented small-molecule synthesis that may have the potential to achieve these
      challenging goals.

PMID- 18080284
TI  - Resistance to glyphosate from altered herbicide translocation patterns.
AB  - Glyphosate-resistant weeds have evolved as a result of the intensive use of
      glyphosate for weed control. An alteration in the way glyphosate is translocated
      within the plant has been identified as a mechanism of glyphosate resistance in
      populations of Lolium rigidum Gaud., L. multiflorum Lam. and Conyza canadensis
      (L.) Cronq. In these resistant plants, glyphosate becomes concentrated in the
      leaves rather than being translocating throughout the plant. This type of
      resistance is inherited as a single dominant or semi-dominant allele. Resistance
      due to reduced translocation appears to be a common mechanism of resistance in L.
      rigidum and C. canadensis, probably because it provides a greater level of
      resistance than other mechanisms. This type of glyphosate resistance also appears
      to reduce the fitness of plants that carry it. This may influence how glyphosate
      resistance can be managed.

PMID- 18080285
TI  - The control of Asian rust by glyphosate in glyphosate-resistant soybeans.
AB  - BACKGROUND: Glyphosate is a widely used broad-spectrum herbicide. Recent studies
      in glyphosate-resistant (GR) crops have shown that, in addition to its herbicidal
      activity, glyphosate exhibits activity against fungi, thereby providing disease
      control benefits. In GR wheat, glyphosate has shown both preventive and curative
      activities against Puccinia striiformis f. sp. tritici (Erikss) CO Johnston and
      Puccinia triticina Erikss, which cause stripe and leaf rusts respectively.
      RESULTS: Laboratory studies confirmed earlier observations that glyphosate has
      activity against Phakopsora pachyrhizi Syd & P Syd which causes Asian soybean
      rust (ASR) in GR soybeans. The results showed that glyphosate at rates between
      0.84 and 1.68 kg ha(-1) delayed the onset of ASR in GR soybeans. However, field
      trials conducted in Argentina and Brazil under natural infestations showed
      variable ASR control from application of glyphosate in GR soybeans. Further field
      studies are ongoing to define the activity of glyphosate against ASR.
      CONCLUSIONS: These results demonstrate the disease control activities of
      glyphosate against rust diseases in GR wheat and GR soybeans.

PMID- 18080286
TI  - Simulation modelling to understand the evolution and management of glyphosate
      resistance in weeds.
AB  - BACKGROUND: A simulation model is used to explore the influence of biological,
      ecological, genetic and operational (management) factors on the probability and
      rate of glyphosate resistance in model weed species. RESULTS: Glyphosate use for
      weed control prior to crop emergence is associated with low risks of resistance.
      These low risks can be further reduced by applying glyphosate in sequence with
      other broad-spectrum herbicides prior to crop seeding. Post-emergence glyphosate
      use, associated with glyphosate-resistant crops, very significantly increases
      risks of resistance evolution. Annual rotation with conventional crops reduces
      these risks, but the proportion of resistant populations can only be reduced to
      close to zero by mixing two of three post-emergence glyphosate applications with
      alternative herbicide modes of action. Weed species that are prolific seed
      producers with high seed bank turnover rates are most at risk of glyphosate
      resistance evolution. The model is especially sensitive to the initial frequency
      of R alleles, and other genetic and reproductive parameters, including weed
      breeding system, dominance of the resistance trait and relative fitness,
      influence rates of resistance. CONCLUSION: Changing patterns of glyphosate use
      associated with glyphosate-resistant crops are increasing risks of evolved
      glyphosate resistance. Strategies to mitigate these risks can be explored with
      simulation models. Models can also be used to identify weed species that are most
      at risk of evolving glyphosate resistance.

PMID- 18080287
TI  - Dose-response effects of clove oil from Syzygium aromaticum on the root-knot
      nematode Meloidogyne incognita.
AB  - BACKGROUND: Clove oil, derived from the plant Syzygium aromaticum (L.) Merr. &
      Perry, is active against various organisms, and was prepared in a soy
      lecithin/detergent formulation to determine concentrations active against the
      root-knot nematode Meloidogyne incognita (Kofoid and White) Chitwood. RESULTS: In
      microwell assays, the mean effective clove oil concentration that reduced egg
      hatch by 50% (EC(50)) was 0.097% (v/v) clove oil; the EC(50) for second-stage
      juvenile (J2) viability was 0.145% clove oil (compared with carrier control
      treatments). Volatiles from 5.0% clove oil reduced nematode egg hatch in water by
      30%, and decreased viability of hatched J2 by as much as 100%. Reductions were
      not as large with nematodes in carrier. In soil trials with J2 recovered from
      Baermann funnels, the EC(50) = 0.192% clove oil (compared with water controls).
      CONCLUSION: The results demonstrated that the tested formulation is active
      against M. incognita eggs and J2, that the EC(50) values for J2 in the microwell
      studies and the soil recovery tests were similar to each other and that direct
      contact with the clove oil is needed for optimal management results with this
      natural product.

PMID- 18080288
TI  - Influence of imidacloprid seed treatments on rice germination and early seedling
      growth.
AB  - BACKGROUND: Seed treatments with the chloronicotinyl insecticide imidacloprid
      (Gaucho 600 FS) were evaluated to determine whether differences in concentration
      and exposure regime influence the germination and early growth of rice. RESULTS:
      Continuous exposure to imidacloprid (4 days at 2000 mg AI L(-1)) significantly (P
      < 0.001) reduced normal germination by an average of 18% across the 15 cultivars
      examined. Nine days after sowing, plants showed no adverse effects from
      continuous imidacloprid treatment during germination, with shoot lengths and root
      system dry weights equalling, or occasionally exceeding (P < 0.05), those of
      untreated plants. Short-term imidacloprid exposure (2 h at 2000 mg L(-1)) at
      initial seed wetting did not affect germination (P > 0.05), and short-term (1 h)
      exposure of 48 h pregerminated seed to imidacloprid (2000 mg L(-1)) similarly had
      no significant effect on early subsequent growth. Plants arising from 48 h
      pregerminated seed exposed to imidacloprid (1 h) at concentrations up to 4000 mg
      L(-1) immediately before sowing were not significantly different from control
      plants at either 9 or 25 days post-sowing. CONCLUSION: Results show that
      imidacloprid will have no adverse effects on plant growth if applied to
      pregerminated rice shortly before sowing. Continuous exposure of seed during
      germination had more pronounced effects, and the initial response of different
      cultivars was highly variable. Cultivars with high levels of sensitivity (such as
      IR72) require further testing before continuous exposure to imidacloprid during
      germination can be recommended.

PMID- 18080289
TI  - Differential expression of cytochrome P450 genes between bromadiolone-resistant
      and anticoagulant-susceptible Norway rats: a possible role for pharmacokinetics
      in bromadiolone resistance.
AB  - BACKGROUND: Anticoagulant resistance in Norway rats, Rattus norvegicus (Berk.),
      has been suggested to be conferred by mutations in the VKORC1 gene, encoding the
      target protein of anticoagulant rodenticides. Other factors, e.g.
      pharmacokinetics, may also contribute to resistance, however. To examine the
      involvement of pharmacokinetics in bromadiolone resistance in male and female
      rats, liver expression profiles of seven cytochrome P450 genes from a Danish
      bromadiolone-resistant rat strain (with an Y139C-VKORC1 mutation) were compared
      with profiles from an anticoagulant-susceptible strain. RESULTS: In the presence
      of bromadiolone, the Cyp2e1, Cyp2c13, Cyp3a2 and Cyp3a3 genes were significantly
      overexpressed, while Cyp2c12 expression was suppressed in resistant female rats
      compared with susceptible females. Relative to susceptible males, resistant males
      showed significant overexpression of the Cyp2a1, Cyp2e1, Cyp3a2 and Cyp3a3 genes.
      On exposure to bromadiolone, females had higher Cyp2e1 expression than males,
      which possibly explains why female rats are generally more tolerant to
      anticoagulants than male rats. CONCLUSION: Results suggest that bromadiolone
      resistance in a Danish strain of Norway rats involves enhanced anticoagulant
      metabolism catalysed by cytochrome P450-2e1, -3a2 and -3a3. This
      pharmacokinetically based bromadiolone resistance is to some extent sex
      differentiated, as female resistance furthermore seems to involve overexpression
      of cytochrome P450-2c13 and suppression of P450-2c12, whereas male resistance
      appears to involve P450-2a1 overexpression.

PMID- 18080290
TI  - Pyrimidinyl-substituted amides and thioureas: syntheses, crystal structure and
      herbicidal activities.
AB  - BACKGROUND: The high herbicidal activities of [1,2,4]triazolo[1,5-c]pyrimidine
      and 2H-1,2,4-thiadiazolo[2,3-a]pyrimidine derivatives suggested the development
      of new fused heterocyclic compounds for application as herbicides. RESULTS: Three
      series of pyrimidinyl-substituted thioureas (4) and amides (5, 6) were
      synthesized, and the typical crystal structure of a 2H-1,2,4-thiadiazolo[2,3
      a]pyrimidine derivative (5a) was determined by X-ray diffraction. All the
      compounds were tested for herbicidal activity against selected weeds. CONCLUSION:
      The series of fused heterocyclic amides 5a to 5d exhibited high herbicidal
      activities both against monocotyledonous weeds (Echinochloa crus-galli L.,
      Sorghum bicolor (L.) Monch., Digitaria sanguinalis (L.) Scop) and against
      dicotyledonous weeds (Amaranthus retroflexus L. and Brassica campestris L.) in
      pre-emergence treatments. In particular, compound 5b at low concentration still
      showed high inhibitory activity against A. retroflexus in pre-emergence
      treatment. Different substituents at the meta positions of the pyrimidine ring
      were found to affect the herbicidal activity.

PMID- 18080291
TI  - Managing the risk of glyphosate resistance in Australian glyphosate- resistant
      cotton production systems.
AB  - BACKGROUND: Glyphosate-resistant cotton varieties are an important tool for weed
      control in Australian cotton production systems. To increase the sustainability
      of this technology and to minimise the likelihood of resistance evolving through
      its use, weed scientists, together with herbicide regulators, industry
      representatives and the technology owners, have developed a framework that guides
      the use of the technology. Central to this framework is a crop management plan
      (CMP) and grower accreditation course. A simulation model that takes into account
      the characteristics of the weed species, initial gene frequencies and any
      associated fitness penalties was developed to ensure that the CMP was
      sufficiently robust to minimise resistance risks. RESULTS: The simulations showed
      that, when a combination of weed control options was employed in addition to
      glyphosate, resistance did not evolve over the 30 year period of the simulation.
      CONCLUSION: These simulations underline the importance of maintaining an
      integrated system for weed management to prevent the evolution of glyphosate
      resistance, prolonging the use of glyphosate-resistant cotton.

PMID- 18080292
TI  - Developmental loss of NT-3 in vivo results in reduced levels of myelin-specific
      proteins, a reduced extent of myelination and increased apoptosis of Schwann
      cells.
AB  - This work investigates the role of NT-3 in peripheral myelination. Recent
      articles, based in vitro, propose that NT-3 acting through its high-affinity
      receptor TrkC may act to inhibit myelin formation by enhancing Schwann cell
      motility and/or migration. Here, we investigate this hypothesis in vivo by
      examining myelination formation in NT-3 mutant mice. On the day of birth, soon
      after the onset of myelination, axons showed normal ensheathment by Schwann
      cells, no change in the proportion of axons which had begun to myelinate, and no
      change in either myelin thickness or number of myelin lamellae. However in
      postnatal day 21 mice, when myelination is substantially complete, we observed an
      unexpected reduction in mRNA and protein levels for MAG and P(0), and in myelin
      thickness. This is the opposite result to that predicted from previous in vitro
      studies, where removal of an inhibitory NT-3 signal would have been expected to
      enhance myelination. These results suggest that, in vivo, the importance of NT-3
      as a major support factor for Schwann cells (Meier et al., (1999) J Neurosci
      19:3847-3859) over-rides its potential role as an myelin inhibitor, with the net
      effect that loss of NT-3 results in degradation of Schwann cell functions,
      including myelination. In support of this idea, Schwann cells of NT-3 null
      mutants showed increased expression of activated caspase-3. Finally, we observed
      significant reduction in width of the Schwann cell periaxonal collar in NT-3
      mutant animals suggesting that loss of NT-3 and resulting reduction in MAG levels
      may alter signaling at the axon-glial interface.

PMID- 18080293
TI  - Ultrastructural plasticity in the rat suprachiasmatic nucleus. Possible
      involvement in clock entrainment.
AB  - Circadian rhythms in mammals are synchronized to the light (L)/dark (D) cycle
      through messages relaying in the master clock, the suprachiasmatic nucleus of the
      hypothalamus (SCN). Here, we provide evidence that the SCN undergoes rhythmic
      ultrastructural rearrangements over the 24-h cycle characterized by day/night
      changes of the glial, axon terminal, and/or somato-dendritic coverage of neurons
      expressing arginine vasopressin (AVP) or vasoactive intestinal peptide (VIP), the
      two main sources of SCN efferents. At nighttime, we noted an increase in the
      glial coverage of the dendrites of the VIP neurons (+29%) that was concomitant
      with a decrease in the mean coverage of the somata (-36%) and dendrites (-43%) of
      these neurons by axon terminals. Conversely, glial coverage of the dendrites of
      AVP neurons decreased (-19%) with parallel increase in the extent of somatal
      (+96%) and dendritic (+52%) membrane appositions involving these neurons. These
      plastic events were concomitant with daily fluctuations in quantitative
      expression of glial fibrillary acidic protein (GFAP), which were then used as an
      index of structural plasticity. The GFAP rhythm appeared to be strictly dependent
      on light entrainment, indicating that structural reorganization of the SCN may
      subserve synchronization of the clock to the L/D cycle. Other results presented
      reinforced this view while showing that circulating glucocorticoid hormones,
      which are known to modulate photic entrainment, were required to maintain
      amplitude of the GFAP rhythm to normal values.

PMID- 18080294
TI  - Type III neuregulin-1 promotes oligodendrocyte myelination.
AB  - The axonal signals that regulate oligodendrocyte myelination during development
      of the central nervous system (CNS) have not been established. In this study, we
      have examined the regulation of oligodendrocyte myelination by the type III
      isoform of neuregulin-1 (NRG1), a neuronal signal essential for Schwann cell
      differentiation and myelination. In contrast to Schwann cells, primary
      oligodendrocytes differentiate normally when cocultured with dorsal root ganglia
      (DRG) neurons deficient in type III NRG1. However, they myelinate type III NRG1
      deficient neurites poorly in comparison to wild type cultures. Type III NRG1 is
      not sufficient to drive oligodendrocyte myelination as sympathetic neurons are
      not myelinated even with lentiviral-mediated expression of NRG1. Mice
      haploinsufficient for type III NRG1 are hypomyelinated in the brain, as evidenced
      by reduced amounts of myelin proteins and lipids and thinner myelin sheaths. In
      contrast, the optic nerve and spinal cord of heterozygotes are myelinated
      normally. Together, these results implicate type III NRG1 as a significant
      determinant of the extent of myelination in the brain and demonstrate important
      regional differences in the control of CNS myelination. They also indicate that
      oligodendrocyte myelination, but not differentiation, is promoted by axonal NRG1,
      underscoring important differences in the control of myelination in the CNS and
      peripheral nervous system (PNS).

PMID- 18080295
TI  - Nanomechanical characterization of polyaniline coated tobacco mosaic virus
      nanotubes.
AB  - Mechanical properties of polyaniline (PANI) coated self-assembled tobacco mosaic
      virus (TMV) nanotubes were measured by nanoindentation with an atomic force
      microscope (AFM) probe. The elastic modulus of PANI/TMV core-shell biocomposite
      tubes (outer diameter: 19 nm, inner diameter: 4 nm, PANI coating thickness: 0.5
      nm) was measured from the AFM force-displacement curves. Structural
      characteristics of the PANI coating, TMV tube, and their interface were studied
      by comparing the mechanical properties of individual constituent materials.
      Results showed that coating with a thin layer of PANI can change the physical and
      chemical properties of TMV nanotubes. The deformation behavior of such core-shell
      biocomposite tubes is discussed in conjunction with the obtained AFM force
      displacement curves, van der Waals interaction between PANI and TMV, and
      mechanical properties of individual constituent materials.

PMID- 18080296
TI  - Tissue engineered cartilage from hTGF beta2 transduced human adipose derived stem
      cells seeded in PLGA/alginate compound in vitro and in vivo.
AB  - Chondrogenic potential of human adipose derived stem cells (hASCs) makes them a
      possible source of seeding cells for cartilage tissue engineering. We aim to
      examine the chondrogenic differentiation of human transforming growth factor
      beta2 (hTGF beta2) transduced hASCs seeded in three-dimensional scaffold in vitro
      and in vivo. In this study, hASCs were isolated from human subcutaneous adipose
      tissue and transduced with a replication deficient adenovirus carrying hTGF beta2
      (Ad5-hTGF beta2), and then the transduced cells were seeded and cultured in
      PLGA/alginate compounds. RT-PCR analysis revealed that Ad5-hTGF beta2 transduced
      hASCs produced aggrecan and collagen type II after 7-day induction in vitro and
      continued throughout the culture period; this was also demonstrated by the
      positive staining of Alcian blue and immunohistochemistry for collagen type II.
      For in vivo study, Ad5-hTGF beta2 transduced hASCs seeded in PLGA/alginate
      compounds were implanted in subcutaneous pockets of nude mice; after 12 weeks,
      the implants were harvested and examined by haematoxylin and eosin staining, AB
      PAS staining, and immunohistochemical analysis, and the results demonstrated the
      formation of cartilage tissue. As a control, all these were not observed in the
      constructs with Ad5-EGFP transduced hASCs. In conclusion, our study demonstrates
      that adenovirus-mediated hTGF beta2 gene transfer is able to induce the hASCs
      into chondrogenic lineage both in vitro and in vivo. Ad5-hTGF beta2 transduced
      hASCs combined with three-dimensional PLGA/alginate compound may be a viable
      method in treating injuries of cartilage.

PMID- 18080297
TI  - Subcutaneous transplantation of autologous oral mucosal epithelial cell sheets
      fabricated on temperature-responsive culture dishes.
AB  - The oral mucosa is an attractive cell source for autologous transplantation in
      human patients who require regenerative therapies of various epithelia. However,
      the time-course of cellular changes in transplanted oral mucosal epithelia at
      ectopic sites remains poorly understood. By applying a rat model, we analyzed
      phenotypic changes in oral mucosal epithelial cell sheets after harvest from
      temperature-responsive culture dishes and subsequent autologous subcutaneous
      transplantation. We used monoclonal antibodies to identify epithelial-specific
      cytokeratins 4, 10, 13, and 14, the stem/progenitor cell marker p63, and
      proliferating cell nuclear antigen, within the regenerated tissues. Transplanted
      oral mucosal epithelial cell sheets proliferated during the first week after
      grafting in conjunction with host inflammation, but then began to degenerate
      afterward with complete disappearance after 3 weeks. Our findings suggest that
      host subcutaneous tissues support proliferation and differentiation of the oral
      mucosal epithelial cell sheets, but are unable to promote maintenance of stem and
      progenitor cells and therefore cannot produce long-term survivability.

PMID- 18080298
TI  - Nanofibrous matrices of poly(lactic acid) and gelatin polymeric blends for the
      improvement of cellular responses.
AB  - Substrates with a nanofibrous morphology are considered as a prospective matrix
      to populate and support cells in the tissue regeneration area. Although the
      nanofibers made of synthetic degradable polymers, including poly(lactic acid)
      (PLA), have been well studied, their poor cell affinity has restricted wider
      applications. Herein, we produced blending nanofibers made of PLA and gelatin to
      improve the cellular responses of PLA. For this, both PLA and gelatin were
      dissolved in an organic solvent, varying the compositions of PLA:gelatin at 1:3
      and 1:1 by weight, and the solutions were electrospun into nanofibers. At all
      compositions, nanofibers could be successfully generated with diameters of
      approximately hundreds of nanometers. The addition of gelatin into PLA markedly
      improved the wettability of the nanofibrous substrate. The osteoblastic cells
      attached and spread well on all the blending nanofibers and pure PLA. In
      particular, the cellular growth was significantly higher on the gelatin-blended
      PLA than on the pure PLA nanofiber. On the basis of this study, the PLA/gelatin
      blending polymeric nanofibers are considered to be useful as a bone cell
      supporting matrix in the tissue regeneration area.

PMID- 18080299
TI  - Fibronectin and pellet suspension culture promote differentiation of human
      mesenchymal stem cells into insulin producing cells.
AB  - Multipotential mesenchymal stem cells (MSCs) isolated from bone marrow can
      differentiate into multiple mesenchymal tissues and exhibit a neuronal phenotype
      under appropriate induction conditions. Methods promoting neural differentiation
      have been adapted to derive insulin producing cells (IPCs) from embryonic stem
      cells, but it remains unclear whether neuronal cell-based differentiation method
      will be able to derive IPCs from MSCs. Using a four-stage differentiation
      protocol which contains neuronal differentiation factor and IPC-conversion
      reagent-nicotinamide, the potential of human MSCs to differentiate into IPCs was
      evaluated by means of reverse transcription-polymerase chain reaction,
      immunostaining, and functional analysis. MSCs in monolayer spontaneously
      expressed genes for islet transcription factors, Nkx6.1 and Ngn3, but did not
      express insulin after treatment in this protocol. Pellet suspension culture and
      the addition of fibronectin enhanced pancreatic differentiation with increase in
      insulin and Glut2 gene expression. Switching of cells to high-glucose culture
      further increased immunostaining for proinsulin and insulin. IPCs secreted
      insulin in response to elevated glucose concentration, which was regulated by
      reagents that increase cyclic AMP production or modify calcium influx. Our data
      suggest that MSCs in the monolayer do not undergo IPC differentiation and pellet
      suspension culture with fibronectin promotes IPCs derived from MSCs.

PMID- 18080300
TI  - Stimulation of osteogenic activity in mesenchymal stem cells by FK506.
AB  - The aim of this study was to investigate the osteogenic induction by tacrolimus
      hydrate (FK506) of rat bone marrow-derived mesenchymal stem cells (MSCs). MSCs
      were cultured in alpha-MEM containing either (1) L-ascorbic acid-2-phosphate
      (AsAP) and beta-glycerophosphate (beta-GP) as a control; (2) AsAP and beta-GP
      plus FK506; (3) AsAP and beta-GP plus Dex; or (4) AsAP and beta-GP plus FK506 and
      Dex. The concentration of FK506 was varied from 5 to 5000 nM to investigate the
      dose-effect relationship. Sixteen days later, cells were harvested for analysis.
      Examination of morphology, alkaline phosphatase (APase) activity, calcium
      deposition, bone nodule formation, osteocalcin mRNA expression, and mineralized
      extracellular matrix formation showed that the osteogenic differentiation of MSCs
      was greatly promoted, bone nodule formation was enhanced, APase activity and the
      expression of osteocalcin mRNA were increased. FK506 was much more effective when
      combined with Dex. The best results were achieved with alpha-MEM containing 0.25
      mM AsAP, 10 mM beta-GP, 10 nM Dex, and 50 nM FK506. Formation of bone in vivo was
      also studied by transplanting MSCs-loaded ceramic cubes subcutaneously into the
      back of rats. Satisfactory results were achieved at 4 and 8 weeks. FK506 should
      be considered for use as an osteogenic agent.

PMID- 18080301
TI  - Porous beta-tricalcium phosphate/collagen composites prepared in an alkaline
      condition.
AB  - Bone substitute materials with natural bone-like structure are considered to be
      favorable for bone regeneration. In this work, porous beta-tricalcium phosphate
      (beta-TCP)/collagen composite consisting of bone-like microstructural units was
      prepared using nanosized beta-TCP particles and alkaline-disassembled collagen.
      The resulting composite showed a good interconnecting porous structure with
      approximately 90% porosity and 100 approximately 300 microm pore size. The pore
      walls were dense, and the combination status of collagen and nanosized beta-TCP
      particles demonstrated that nanosized beta-TCP particles tightly connected
      collagen microfibrils as a bone-like microstructural unit. MTT and alkaline
      phosphatase (ALP) assays showed that the porous composite had enhanced effects on
      cellular proliferation and activity of osteoblast compared with a control of pure
      collagen. It is suggested that the adoption of nanosized beta-TCP particles is a
      main contribution to the formation of the composite with a bone-like
      microstructural unit, and the unique microstructure could be a main role for the
      composite to have the positive influence on osteoblast cell proliferation.

PMID- 18080302
TI  - Antibacterial properties and corrosion resistance of Cu and Ag/Cu porous
      materials.
AB  - The porous materials of Cu and Ag/Cu were successfully prepared by the
      electrodeposition on a precursor of conventional polyamide foam. The
      microstructure of the porous materials was observed by scanning electron
      microscope. Their porosity and specific surface area were measured. The
      inhibition effect of Cu porous materials against E. coli was also investigated.
      The broad-spectrum of antibiosis of the Cu and Ag/Cu porous materials were
      characterized. The corrosion resistance of Cu, Ag/Cu coatings was also compared.
      The shape and size of pores are uniform in three directions for the porous
      materials. Their porosity may reach above 95% and specific surface area is beyond
      12.8 m(2)/m(3). The antibacterial test results show that the Cu porous materials
      not only exhibited high antibacterial effect and good broad-spectrum
      antibacterial properties, but also excellent persistent antibacterial effects;
      the antibacterial effects, and broad-spectrum of antibiosis were greatly improved
      through the deposition of a thin Ag coating on the surface of Cu porous material.

PMID- 18080303
TI  - Mechanism of calcium disilicide-induced calcification of crystalline silicon
      surfaces in simulated body fluid under zero bias.
AB  - A dry-etch spark ablation method was used to produce calcium disilicide
      (CaSi2/Si) layers on silicon surfaces, and their biomineralization under zero
      bias was followed by means of scanning electron microscopy, X-ray energy
      dispersive analysis, and Raman spectroscopy. CaSi2/Si wafers are bioinert at 25
      degrees C and bioactive at 37 degrees C. Mechanistic insights regarding
      biomineralization were derived from an analysis of film growth morphology and
      chemical composition after various soaking periods in standard simulated body
      fluid (SBF). Changes in CaSi2/Si calcification behavior as a function of reaction
      temperature and pH, SBF concentration, and various surface modification processes
      were also employed for this purpose. During CaSi2/Si calcification under zero
      bias, calcium phosphate (CaP) growth is strongly dependent on the structural
      degradation of CaSi2/Si grains. Surface silanol groups, initially present on the
      as-prepared material, cannot induce CaP nucleation, which begins only upon
      delamination of CaSi2/Si layers. The calcium phosphate phases, which are present
      during various growth stages, possibly include a combination of Mg-substituted
      whitlockite, monetite, and tricalcium phosphate.

PMID- 18080304
TI  - Histologic and histomorphometric evaluation of early and immediately loaded
      implants in the dog mandible.
AB  - New bone formation around US III OSSTEM implants after early and immediate
      loading was evaluated in this study. Three premolars and the first and second
      molars were first removed from the left mandible of five dogs. At 3 weeks after
      extraction of the teeth in the left mandible, the corresponding teeth in the
      right mandibles were removed. After 12 weeks of bone healing, five implants were
      placed in the left mandible. At 3 weeks after placement of implants in the left
      mandible, another five were placed in the right mandible. At the time of placing
      implants in the right mandible, four implants on each side were restored using a
      fixed provisional restoration. The anterior-most implant was not loaded and was
      used as controls. Periotest measurements performed immediately after implantation
      and after 16 weeks loading indicated implant stability for all groups tested. At
      16 weeks after loading, the rate of peri-implant bone formation for the early
      loaded, immediately loaded (IL), and control implants were observed to be 75.00,
      73.37, and 62.04%, respectively. It was thus concluded that early stability was
      achieved in early and IL implants using fixed provisional restoration, thereby
      resulting in the high rate of peri-implant bone formation.

PMID- 18080305
TI  - Comments from the editors.

PMID- 18080306
TI  - Biodegradable and thermoreversible hydrogels of poly(ethylene glycol)
      poly(epsilon-caprolactone-co-glycolide)-poly(ethylene glycol) aqueous solutions.
AB  - The aqueous solutions of triblock copolymers of poly(ethylene glycol)
      poly(epsilon-caprolactone-co-glycolide)-poly(ethylene glycol) [PEG-P(CL-GA)-PEG]
      undergoing sol-gel transition as the temperature increases from 20 to 60 degrees
      C were successfully prepared. The thermogelling block copolymers were synthesized
      by subtle control of the hydrophilic/hydrophobic balance and the chain
      microstructures. The amphiphilic block copolymer formed micelles in aqueous
      solution, and the micelle aggregated as the temperature increased. The sol-gel
      transition of the copolymer aqueous solutions was studied focusing on the
      structure-property relationship. GA was incorporated into the polymer chain to
      prevent crystallization of PCL component and increase the polymer degradation. It
      is expected to be a promising long-term delivery system for pH-sensitive drugs,
      proteins, and genes.

PMID- 18080307
TI  - Adhesion of protein residues to substituted (111) diamond surfaces: an insight
      from density functional theory and classical molecular dynamics simulations.
AB  - Protein-repellent diamond coatings have great potential value for surface
      coatings on implants and surgical instruments. The design of these coatings
      relies on a fundamental understanding of the intermolecular interactions involved
      in the adhesion of proteins to surfaces. To get insight into these interactions,
      adhesion energies of glycine to pure and Si and N-doped (111) diamond surfaces
      represented as clusters were calculated in the gas phase, using density
      functional theory (DFT) at the B3LYP/6-31G* level. The computed adhesion energies
      indicated that adhesion of glycine to diamond surface may be modified by
      introducing additional elements into the surface. The adhesion was also found to
      induce considerable change in the conformation of glycine when compared with the
      lowest-energy conformer of the free molecule. In the Si and N-substituted diamond
      clusters, notable changes in the structures involving the substituents atoms when
      compared with smaller parent molecules, such as 1-methyl-1-silaadamantane and 1
      azaadamantane, were detected. Adhesion free energy differences were estimated for
      a series of representative peptides (hydrophobic Phe-Gly-Phe, amphiphilic Arg-Gly
      Phe, and hydrophilic Arg-Gly-Arg) to a (111) diamond surface substituted with
      different amounts of N, Si, or F, using molecular dynamics simulations in an
      explicit water environment employing a Dreiding force field. The calculations
      were in agreement with the DFT results in that adsorption of the studied peptides
      to diamond surface is influenced by introducing additional elements to the
      surface. It has been shown that, in general, substitution will enhance
      electrostatic interactions between a surface and surrounding water, leading to a
      weaker adhesion of the studied peptides.

PMID- 18080308
TI  - Mechanical and chemical characteristics of an autologous glue.
AB  - The study evaluates the mechanical and chemical characteristics of autologous
      surgical glue made by mixing ultrafiltered plasma with glutaraldehyde (GTA).
      Human albumin 200 g/L mixed with different concentrations of GTA (25, 50, 75, or
      100 g/L) was used as a single protein set-up for testing tensile strength,
      elasticity, and rate of crosslinking. Subsequently, ultrafiltered canine or human
      plasma to obtain autologous glue replaced human albumin. BioGlue, a surgical
      glue, and Tissucol Duo, a fibrin sealant, were used as controls. Tensile strength
      of human albumin 200 g/L mixed with 75 g/L GTA is 825 +/- 109 N versus 672 +/-
      167 N for BioGlue. Ultrafiltered canine plasma showed a maximum tensile strength
      of 634 +/- 137 N when mixed with GTA 75 g/L. For human plasma, the maximum
      tensile strength of 436 +/- 69 N was reached after mixing with GTA 25 g/L.
      Autologous glue had a higher elasticity of 144 +/- 66 N versus 322 +/- 104 N for
      BioGlue at maximum load. Autologous glues for vascular repair can be easily
      prepared out of the patient's plasma. The optimal characteristics, compared to
      BioGlue, are obtained for ultrafiltered canine and human plasma by mixing with a
      GTA concentration of 50-75 g/L and 25-50 g/L, respectively. The autologous glue
      will exert less tensile strength than BioGlue but has a better compliance. In
      case where no plasma can obtained from the patient, mixing human albumin 200 g/L
      with GTA 75 g/L can be an alternative to BioGlue.

PMID- 18080309
TI  - Paclitaxel release from single and double-layered poly(DL-lactide-co
      glycolide)/poly(L-lactide) film for biodegradable coronary stent application.
AB  - Our laboratory has been developing a completely biodegradable coronary stent
      which is made of bilayers of biodegradable polyesters. This article presents the
      preliminary work done to exploit the drug delivery potential of such a polymeric
      stent. An antiproliferative drug (paclitaxel) was added either only to the top
      layer or to both layers and the in vitro release profiles were monitored for up
      to 90 days. Within 90 days, the measured paclitaxel release was almost entirely
      from the P(DL)LGA layer. In general, the release profiles show three distinct
      stages: (a) extremely slow diffusional release, (b) accelerated diffusion
      degradation release, and (c) saturation. Separate degradation studies (water
      absorption, molecular weight reduction, weight loss, and surface topography) were
      also conducted to better understand the observed release behavior.

PMID- 18080310
TI  - Effects of substitution degree of photoreactive groups on the properties of UV
      fabricated chitosan scaffold.
AB  - Hydroxypropyl chitosan (HPCS), a water-soluble chitosan derivate, was modified by
      introducing photoreactive azide groups (4-azidobenzoic acid, Az-) to the amino
      groups of HPCS, resulting in a photocrosslinkable Az-HPCS. Novel porous chitosan
      scaffolds thus were fabricated by ultraviolet (UV) light irradiation of Az-HPCS
      aqueous solutions. Fourier transform infrared spectroscopy, scanning electron
      microscopy, measurement of pore size and porosity, mechanical test, swelling
      test, in vitro biodegradation determination were used to analyze the effects of
      degree of substitution (DS) of Az-groups on the properties of the scaffolds. When
      DS of Az-groups increased from 2.8% to 5.6%, we found that (i) the pore size of
      Az-HPCS scaffolds increased by about twofold and the porosity increased slightly,
      probably due to more N(2) released from the crosslinking reaction with the
      increase of DS; (ii) both the tensile stress and strain increased by about
      threefold, relating to the increase of joint points, pore size, and porosity at a
      relative high DS; (iii) the swelling ratio and degradation rate decreased with
      the increase of Az-DS, because of the forming of a more compact network
      structure. Preliminary data of cell culture on Az-HPCS scaffold suggested its
      potential applicability for tissue engineering.

PMID- 18080311
TI  - Liver tissue responses to gelatin and gelatin/chitosan gels.
AB  - Gelatin and gelatin/chitosan gels, crosslinked using glutaraldehyde, were
      previously developed as substrates for three-dimensional cell-assembly
      techniques. In this study, the biocompatibility and biodegradation of gelatin and
      gelatin/chitosan gels were evaluated following implantation in rat livers for
      periods up to 16 weeks. The two gels were characterized by different inflammatory
      responses and degradation rates. The gelatin/chitosan gel is more efficient in
      inducing fibrin formation and vascularization at the implant-host interface. The
      degrees of inflammatory reaction for the gelatin/chitosan gel were significantly
      stronger than the gelatin gel. Advanced biodegradation of the gelatin gels was
      observed. These data indicate that the gelatin gel has better liver tissue
      biocompatibility and a faster biodegraded rate than the gelatin/chitosan gel.

PMID- 18080312
TI  - Shell-core imprinted polyacrylamide crosslinked chitosan for albumin removal from
      plasma.
AB  - Molecularly imprinted polymeric beads were prepared using albumin as the
      imprinted molecule, acrylamide as the functional monomer, and epichlorhydrin
      crosslinked chitosan beads as the supporting matrix. The recognition and binding
      of the imprinted beads was also tested with human plasma for the targeted removal
      of HSA. Plasma is a rich source of biochemical products that can act as
      biomarkers of disease or physiological status of a patient. The application of
      current proteomic technologies in the search for potential diagnostic/prognostic
      indicators in the plasma of patients is limited by highly abundant albumin that
      constitute >60% of the total plasma proteins. Removal of abundant proteins will
      help in the discovery and detection of less abundant proteins that may prove to
      be informative. The adsorption capacities of the imprinted polymeric beads for
      pure human serum albumin and plasma albumin were estimated as 92% and 80%,
      respectively. The easy preparation protocol of derivatised beads and good protein
      recognition properties make them attractive for biotechnologic approaches.

PMID- 18080313
TI  - Synthesis and characterization of collagen-chitosan-hydroxyapatite artificial
      bone matrix.
AB  - In this study, a new artificial bone matrix was constructed with collagen and
      Ca(5)(PO(4))(3)OH (hydroxyapatite/HA) which are the main components of natural
      bone. To improve the property of the artificial bone matrix, chitosan (CS), a
      kind of positive charged polysaccharide, was crosslinked into the scaffolds.
      Solid-liquid phase separation method was used to shape 3D porous structure
      benefited for cells growing into. The artificial bone matrix was investigated by
      transmission electron microscopy, scanning electron microscopy, and electron
      spectroscopy for chemical analysis, etc. for structures and characteristics. And
      its ability of bone repair was investigated by orthotope bone defect reparation
      in vivo. The results showed that the artificial bone matrix was a porousscaffold
      with three-dimension interconnected fiber microstructure. HA particles were
      dispersed evenly among collagen fiber and CS was modified on the surface of
      collagen fiber. It was indicated that this artificial bone matrix could be used
      as a bone substitute with outstanding properties.

PMID- 18080314
TI  - High definition.

PMID- 18080315
TI  - Population genetic studies of Alouatta belzebul from the Amazonian and Atlantic
      Forests.
AB  - Cytochrome b DNA sequence data (ca. 1,140 bp) of 66 Alouatta belzebul from the
      Amazonian and the Atlantic Forests of Brazil were used for phylogenetic
      reconstructions and population studies. Our sample consisted of 60 specimens from
      the Amazonian Forest (captured in 1984 and 1998 in Para-PA state) and six
      specimens from the Atlantic Forest (Paraiba-PB state). We found 32 haplotypes, 23
      in PA-1984 (with 12 present in more than one individual), 11 in PA-1998 (with two
      present in more than one individual), and a single haplotype in the PB sample.
      Animals from PA-1984 and PA-1998 shared three haplotypes while animals from Para
      and Paraiba did not share any haplotype. We found 57 variable sites, consisting
      of 53 transitions and four transversions, with most replacements occurring at
      third codon position (77.19%) and less frequently at first and second positions
      (10.53 and 12.28%, respectively). Genetic distance between all haplotypes varied
      between 0 and 1.2%. Nucleotide diversity estimates between PA-1984 haplotypes and
      PA-1998 haplotypes were the same (pi=0.01), and haplotype diversity estimates
      were very similar (h=0.96 and 0.93 for PA-1984 and PA-1998, respectively).
      Maximum parsimony, median-joining, split decomposition, and TCS showed that PA
      and PB haplotypes had not drastically diverged and that subsequent radiation
      within these regions was not apparent. No temporal structure was found between PA
      1984 and PA-1998. The sum of square deviation estimate for PA-1984 equaled 0.01
      (P=0.23), in agreement with a hypothetical model of sudden expansion contrary to
      PA-1998 whose sum of square deviation estimate (0.40; P=0.04) was not compatible
      with this model, although the small sample size of PA-1998 as well as the smaller
      area of capture could have also accounted for this result. Fu's F(s) and R(2)
      statistical neutrality tests corroborated these propositions. Lack of drastic
      differentiation was attributable to the once existing connection between the
      Atlantic and the Amazonian forests at a non-distant past.

PMID- 18080316
TI  - Patterns of correlation and covariation of anthropoid distal forelimb segments
      correspond to Hoxd expression territories.
AB  - Anthropoids in general and hominoids in particular exhibit differential
      adaptations in forearm and digital skeletal proportions to a diverse array of
      locomotor modes. Hox genes act as selector genes with spatially regulated
      expression patterns during development. Their expression in the forelimb appears
      to define modules that specify differential skeletal growth. Here we explore
      forelimb skeletal proportions in a large sample of anthropoids from a background
      provided by Hoxd expression patterns in late-stage murine embryonic forelimbs.
      Interspecific correlation and principal components analyses of primate forelimb
      data indicate that morphological variation in anthropoids reflects well-defined
      developmental modules downstream of Hoxd expression. The phalanges of digit one
      appear to represent a single growth module, whereas the metacarpals and manual
      phalanges of the posterior digits correspond to a second, independent, expression
      territory that extends proximally into the distal zeugopod. In particular,
      hominoids show very high correlations among the posterior digits and the
      independence of digit one. In addition, the distal radius is generally highly
      correlated with the posterior digits and not digit one. Relying on established
      functional differences among Hox paralogs, we present a model that parsimoniously
      explains hominoid forearm and digital proportions as a consequence of downstream
      effects of Hox. We, therefore, suggest that Hox-defined developmental modules
      have served as evolutionary modules during manual evolution in anthropoids.

PMID- 18080317
TI  - Distinct osteoblastic differentiation potential of murine fetal liver and bone
      marrow stroma-derived mesenchymal stem cells.
AB  - Bone marrow-derived mesenchymal stem cells (MSC) are able to differentiate into
      osteoblasts under appropriate induction. Although MSC-derived osteoblasts are
      part of the hematopoietic niche, the nature of the stromal component in fetal
      liver remains elusive. Here, we determined the in vitro osteoblastic
      differentiation potential of murine clonal fetal liver-derived cells (AFT024,
      BFC012, 2012) in comparison with bone marrow-derived cell lines (BMC9, BMC10).
      Bone morphogenetic protein-2 (BMP2) increased alkaline phosphatase (ALP)
      activity, an early osteoblastic marker, in AFT024 and 2012 cells, whereas
      dexamethasone had little or no effect. BMP2, but not dexamethasone, increased ALP
      activity in BMC9 cells, and both inducers increased ALP activity in BMC10 cells.
      BMP2 increased ALP mRNA in AFT024, 2012 and BMC9 cells. By contrast, ALP was not
      detected in BMC10 and BFC012 cells. BMP2 and dexamethasone increased osteopontin
      and osteocalcin mRNA expression in 2012 cells. Furthermore, bone marrow-derived
      cells showed extensive matrix mineralization, whereas fetal liver-derived cell
      lines showed no or very limited matrix mineralization capacity. These results
      indicate that the osteoblast differentiation potential differs in bone marrow and
      fetal liver-derived cell lines, which may be due to a distinct developmental
      program or different microenvironment in the two hematopoietic sites.

PMID- 18080318
TI  - Hand preference during unimanual and bimanual reaching actions in Sichuan snub
      nosed monkeys (Rhinopithecus roxellana).
AB  - Hand preferences were investigated during one unimanual action (food-reaching)
      and one bimanual action (mount-reaching) in a semi-free-ranging group of Sichuan
      snub-nosed monkeys (Rhinopithecus roxellana) in Zhouzhi National Nature Reserve,
      Qinling Mountains of China. Nine of 14 individuals tested on the unimanual food
      reaching action and all six individuals tested on the bimanual mount-reaching
      action exhibited a manual preference. Both significant right- and left-handed
      preferences were observed in the two actions. Sex did not affect either direction
      or strength of hand preference in the unimanual action. Hand preference for the
      bimanual action was stable over time, and the strength of hand preference was
      significantly stronger in the bimanual action than in the unimanual action.

PMID- 18080319
TI  - Tyrosine phosphorylation controls nuclear localization and transcriptional
      activity of Ssdp1 in mammalian cells.
AB  - The LIM-HD proteins interact with different cofactors, including Ssdp1 to
      regulate development in a diverse range of species. The single stranded DNA
      binding protein (Ssdp1) is a member of an evolutionarily conserved family of
      proteins that regulate critical transcriptional processes during embryonic
      development. Ssdp1 is localized predominantly in the cytoplasm of 293T cells but
      is translocated to the nucleus when co-transfected with Lck, a member of the Src
      family of non-receptor tyrosine kinases. The Src tyrosine kinase inhibitor PP2
      blocked the nuclear translocation of Ssdp1. Western blot analysis showed that co
      expression of Ssdp1 and Lck in 293T cells induces Ssdp1 phosphorylation. Mutation
      of the Ssdp1 N terminal tyrosine residues 23 and 25 markedly reduced both the
      phosphorylation and the nuclear localization of Ssdp1. Lck enhanced the
      transcriptional activity of Ssdp1 in the context of known components of a LIM
      homeodomain (LIM-HD)/cofactor complex. We propose that phosphorylation involving
      N-terminal tyrosine residues of Ssdp1 is a means of regulating its nuclear
      localization and subsequent transcriptional activation of LIM-HD complexes.

PMID- 18080320
TI  - Two modes of ERK activation by TNF in keratinocytes: different cellular outcomes
      and bi-directional modulation by vitamin D.
AB  - Inflammation, elicited in the skin following tissue damage or pathogen invasion,
      may become chronic with deleterious consequences. Tumor necrosis factor (TNF) is
      a key mediator of cutaneous inflammation and the keratinocyte an important
      protagonist of skin immunity. Calcitriol, the hormonally active vitamin D
      metabolite, and its analogs attenuate epidermal inflammation and inhibit the
      hyperproliferation of keratinocytes associated with the inflammatory disorder,
      psoriasis. Since activation of extracellular signal-regulated kinase (ERK)
      promotes keratinocyte proliferation and mediates epidermal inflammation, we
      studied the effect of calcitriol on ERK activation in HaCaT keratinocytes exposed
      to the ubiquitous inflammatory cytokine TNF. By using the EGF receptor (EGFR)
      tyrosine kinase inhibitor, AG1487 and the Src family inhibitor, PP-1, we
      established that TNF activated ERK in an EGFR and Src dependent and an EGFR and
      Src independent modes. EGFR dependent activation resulted in the upregulation of
      the transcription factor, c-Fos, while the EGFR independent activation mode was
      of a shorter duration, did not affect c-Fos expression but induced IL-8 mRNA
      expression. Pretreatment with calcitriol, enhanced TNF-induced EGFR-Src dependent
      ERK activation and tyrosine phosphorylation of the EGFR, but abolished the EGFR
      Src independent ERK activation. These effects were mirrored by enhancement of c
      Fos and inhibition of IL-8 induction by TNF. Treatment with calcitriol increased
      the rate of the de-phosphorylation of activated ERK, accounting for the
      inhibition of EGFR-Src independent ERK activation by TNF. It is possible that
      effects on the ERK cascade contribute to the effects of calcitriol and its
      synthetic analogs on cutaneous inflammation and keratinocyte proliferation.

PMID- 18080321
TI  - Disease-modifying effects of glucosamine HCl involving regulation of
      metalloproteinases and chemokines activated by interleukin-1beta in human primary
      synovial fibroblasts.
AB  - The purpose of this study was to investigate the possible involvement of synovium
      in cartilage destruction in osteoarthritis (OA) patients. Using human primary
      synovial fibroblasts (HPSFs), we examined the effects of glucosamine (GLN) on the
      regulation of the expression of matrix metalloproteinases (MMP-1, -2, and -13)
      and chemokines (IL-8, MCP-1, and RANTES) as well as the involvement of MAPK
      signal pathways (JNK, ERK, and p-38) and the transcription factor of NF-kappaB on
      the present or absence of interleukin (IL)-1beta. Our experiments showed that
      protein production and mRNA expressions of MMP-1, MMP-3, MMP-13, IL-8, MCP-1, and
      RANTES were downregulated by treatment with glucosamine in HPSFs. The results
      further showed that GLN could inhibit IkappaBalpha phosphorylation and
      IkappaBalpha degradation leading to inhibition of the translocation of NF-kappaB
      to nuclei. However, GLN upregulated MAPKs pathways in HPSFs cells with or without
      IL-1beta. The results suggest that the inhibition of MMP-1, -3, and -13
      expressions as well as IL-8, MCP-1, and RANTES productions by GLN might mediate
      suppression of NF-kappaB signal pathways, and HPSFs seem to have a potential
      functions as an alternative source of MMPs and chemokines for inducing the
      degradation of cartilage in OA.

PMID- 18080322
TI  - Noonan syndrome: psychological and psychiatric aspects.
AB  - Although Noonan syndrome (NS) is a disorder with a relatively high prevalence,
      virtually no information in adult patients is available about the psychological
      and psychopathological profile. In the present clinical report the first series
      of 10 NS patients from an ongoing project is presented. The purpose of the study
      is to investigate the psychopathology, social cognition and adaptation as well as
      the quality of life in NS patients aged 16 years or more. PTPN11 mutations were
      present in six patients and KRAS and SOS1 in one patient, respectively. In two
      patients no known mutation was found. The results demonstrate a variable level of
      intelligence and suggest moderately impaired social cognition in terms of emotion
      recognition and alexithymia. In some patients mild signs of anxiety and lowered
      mood are found that, however, do not meet the criteria for a specific psychiatric
      disorder. It is concluded that NS in adults is associated with a behavioral
      phenotype in which deficiencies in social and emotional recognition and
      expression may be key elements.

PMID- 18080323
TI  - Pseudoarthrosis of the clavicle and copper beaten skull associated with
      chromosome 10p11.21p12.1 microdeletion.
AB  - Congenital pseudoarthrosis of the clavicle (CPC) has been described in several
      genetic conditions including Floating-Harbor and Goltz syndromes, but rarely as a
      prompt to specific cytogenetic abnormalities. We report on a case of a de novo
      10p11.21p12.1 microdeletion in a boy with multiple problems including a beaten
      copper appearance of the cranium on skull X-ray and pseudoarthrosis of the right
      clavicle. This is the first description of these particular skeletal findings in
      the context of a chromosome 10p deletion.

PMID- 18080324
TI  - Genetic screening for reproductive purposes at school: is it a good strategy?
AB  - Thalassemia and Tay-Sachs disease were the first diseases in which the criteria
      for heterozygote genetic screening were met and successful programs for
      reproductive purposes were initiated in populations at risk. However, many of the
      couples first discover the possibility of genetic screening during pregnancy and
      efforts are made to bring couples to consider screening tests before the first
      pregnancy. In this context, high school offers a convenient setting and several
      pilot programs have been very successful. All evaluations of these programs found
      that education plays a critical role in allowing informed decisions and
      minimizing the possible harms. While it has been suggested that high school may
      be the best setting for reproductive screening programs, guidelines of several
      societies of human genetics recommend the use of carrier screening only in
      individuals older than 18 years. There are several other problems related to
      genetic screening programs at school and some are discussed in the review. Our
      opinion is that school should be a place to provide the tools for decisions by
      education only; while the option to have the genetic tests later in life or in
      another setting should be offered to the students as part of the education
      session. This may allow the students to decide when and where to have a genetic
      test.

PMID- 18080325
TI  - Bile duct anomalies in a male child with Noonan syndrome: a case for ras and
      notch pathway synergism.

PMID- 18080326
TI  - Bannayan-Riley-Ruvalcaba syndrome with posterior subcapsular congenital cataract
      and a consensus sequence splicing PTEN mutation.

PMID- 18080327
TI  - Priorities for public health research on craniosynostosis: summary and
      recommendations from a Centers for Disease Control and Prevention-sponsored
      meeting.
AB  - On June 8-9, 2006, the National Center on Birth Defects and Developmental
      Disabilities at the Centers for Disease Control and Prevention held a meeting
      entitled "Prioritizing a Public Health Research Agenda for Craniosynostosis". The
      meeting goals were to review current knowledge in the area, discuss research
      gaps, and identify future priorities for public health research. Participants
      with a broad range of expertise (including clinical and molecular genetics,
      cranial morphology, epidemiology, pediatrics, psychology, public health, and
      surgery) contributed to the development of the research agenda. Meeting
      participants were asked to consider public health significance and feasibility
      when identifying areas of priority for future public health research.
      Participants identified several priorities, including the need to better
      delineate the prevalence and phenotype of craniosynostosis (CS); to identify
      factors important in the causation of CS (including potentially modifiable
      environmental risk factors as well as genes involved in isolated CS and gene-gene
      and gene-environment interactions); and to better understand short- and long-term
      outcomes of CS (e.g., surgical, neurocognitive and neuropsychological outcomes,
      psychological adjustment, and social relationships) and issues related to
      clinical care that could affect those outcomes. The need for improved
      collaboration among clinical treatment centers and standardization of data
      collection to address these priorities was emphasized. These priorities will be
      used to guide future public health research on CS.

PMID- 18080328
TI  - Complex rearrangement of chromosomes 7q21.13-q22.1 confirms the ectrodactyly
      deafness locus and suggests new candidate genes.
AB  - Complex chromosomal rearrangements with more than two breakpoints are rare. We
      report on a 5-year-old girl, evaluated because of psychomotor delay, ectrodactyly
      of right hand and feet, craniofacial dysmorphic features, cleft palate, deafness,
      and tetralogy of Fallot. A standard karyotype suggested a small intrachromosomal
      duplication of chromosome 7q. The chromosomal rearrangement was characterized by
      mBAND, which disclosed a reciprocal interstitial translocation
      t(7;8)(q21q22;q23q24). FISH analysis and array-CGH analysis showed a paracentric
      inversion of 7q and a microdeletion of 7q21.13. The parents had normal
      chromosomes. The deletion found in the present patient confirms that candidate
      region of ectrodactyly-deafness (OMIM 220600) maps to 7q21 and suggests new
      candidate genes for that disorder. This patient also had facial features
      reminiscent of tricho-rhino-phalangeal syndrome and one chromosome breakpoint
      involved band 8q24, a locus for this disorder. In addition, FOG1 gene maps to
      8q23 and has been implicated in a subset of subjects with tretralogy of Fallot.
      We suggest that the aberration of 8q may have contributed to her facial and
      cardiac findings.

PMID- 18080329
TI  - Real-time cellular uptake of serotonin using fluorescence lifetime imaging with
      two-photon excitation.
AB  - The real-time uptake of serotonin, a neurotransmitter, by rat leukemia mast cell
      line RBL-2H3 and 5-hydroxytryptophan by Chinese hamster V79 cells has been
      studied by fluorescence lifetime imaging microscopy (FLIM), monitoring
      ultraviolet (340 nm) fluorescence induced by two-photon subpicosecond 630 nm
      excitation. Comparison with two-photon excitation with 590 nm photons or by three
      photon excitation at 740 nm shows that the use of 630 nm excitation provides
      optimal signal intensity and lowered background from auto-fluorescence of other
      cellular components. In intact cells, we observe using FLIM three distinct
      fluorescence lifetimes of serotonin and 5-hydroxytryptophan according to
      location. The normal fluorescence lifetimes of both serotonin (3.8 ns) and 5
      hydroxytryptophan (3.5 ns) in solution are reduced to approximately 2.5 ns
      immediately on uptake into the cell cytosol. The lifetime of internalized
      serotonin in RBL-2H3 cells is further reduced to approximately 2.0 ns when stored
      within secretory vesicles.

PMID- 18080330
TI  - NAD(+)-dependent DNA ligase: a novel target waiting for the right inhibitor.
AB  - DNA ligases (EC.6.5.1.1) are key enzymes that catalyze the formation of
      phosphodiester bonds at single stranded or double stranded breaks between
      adjacent 5' phosphoryl and 3' hydroxyl groups of DNA. These enzymes are important
      for survival because they are involved in major cellular processes like DNA
      replication/repair and recombination. DNA ligases can be classified into two
      groups on the basis of their cofactor specificities. NAD(+)-dependent DNA ligases
      are present in bacteria, some entomopox viruses and mimi virus while ATP
      dependent DNA ligases are ubiquitous. The former have recently been drawing a lot
      of attention as novel targets for antibiotics to overcome current drug resistance
      issues. Currently a diverse range of inhibitors have been identified. There are
      several issues to be addressed in the quest for optimized inhibitors of the
      enzyme. In the first part of the review we summarize current structural work on
      these enzymes. Subsequently we describe the currently available classes of
      inhibitors. We also address modalities to improve the specificity and potencies
      of new inhibitors identified using protein structure based rational approaches.
      In conclusion, NAD(+)-dependent ligases show great promise and represent a novel
      drug target whose time has come.

PMID- 18080331
TI  - Flavonoids as RTK inhibitors and potential anticancer agents.
AB  - Tyrosine kinase receptors (RTKs) play a crucial role in the regulation of the
      cell division cycle. Currently more than 50 RTKs divided into several subfamilies
      have been described. The inhibition of these enzymes has emerged as an important
      research-area. Compounds able to inhibit the activity of these enzymes are
      expected to display antiproliferative properties. Flavonoids are representative
      of various small molecules acting as RTK inhibitors. These naturally occurring
      compounds are able to bind to the ATP-binding site of several kinases. The most
      plausible current hypothesis explaining the action of these substances on kinases
      is that the chromenone moiety of the flavonoid acts as a mimetic of the adenine
      moiety of ATP, the receptor co-factor. In this review, we report recent results
      on the activity of natural and synthetic derivatives of flavonoids as inhibitors
      of RTKs. Mechanistic aspects, the therapeutic usefulness, and the potential
      clinical use are discussed.

PMID- 18080332
TI  - 2007 Focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous
      coronary intervention. A report of the American College of Cardiology/American
      Heart Association Task Force on Practice Guidelines.

PMID- 18080333
TI  - GDNF fusion protein for targeted-drug delivery across the human blood-brain
      barrier.
AB  - Glial-derived neurotrophic factor (GDNF) is a neurotrophin that could be
      developed as a neurotherapeutic for Parkinson's disease, stroke, and motor neuron
      disease. However, GDNF does not cross the blood-brain barrier (BBB). Human GDNF
      was re-engineered by fusion of the mature GDNF protein to the carboxyl terminus
      of the chimeric monoclonal antibody (MAb) to the human insulin receptor (HIR).
      The HIRMAb-GDNF fusion protein is bi-functional, and both binds the HIR, to
      trigger receptor-mediated transport across the BBB, and binds the GDNF receptor
      (GFR)-alpha1, to activate GDNF neuroprotection pathways behind the BBB. COS cells
      were dual transfected with the heavy chain (HC) and light chain fusion protein
      expression plasmids, and the HC of the fusion protein was immunoreactive with
      antibodies to both human IgG and GDNF. The HIRMAb-GDNF fusion protein bound with
      high affinity to the extracellular domain of both the HIR, ED(50) = 0.87 +/- 0.13
      nM, and the GFRalpha1, ED(50) = 1.68 +/- 0.17 nM. The HIRMAb-GDNF fusion protein
      activated luciferase gene expression in human neural SK-N-MC cells dual
      transfected with the c-ret kinase and a luciferase reporter gene under the
      influence of the rat tyrosine hydroxylase promoter, and the ED(50), 1.68 +/- 0.45
      nM, was identical to the ED(50) in the GFRalpha1 binding assay. The fusion
      protein was active in vivo in a rat middle cerebral artery occlusion model, where
      the stroke volume was reduced 77% (P < 0.001). In conclusion, these studies
      describe the re-engineering of GDNF, to make this neurotrophin transportable
      across the human BBB.

PMID- 18080334
TI  - Ensuring safe, quality care for hospitalized people with advanced illness, a core
      obligation for hospitalists.

PMID- 18080335
TI  - Combination of clonidine and diuretic in cirrhotic ascites with activated
      sympathetic nervous system: Would it be a magical bullet?

PMID- 18080336
TI  - Common myths about caring for patients with terminal illness: opportunities to
      improve care in the hospital setting.
AB  - BACKGROUND: Shortcomings in the quality of care of hospitalized patients at the
      end of life are well documented. Although hospitalists and residents are often
      involved in the care of hospitalized patients with terminal illness, little is
      known about their knowledge and beliefs concerning terminal illness, despite the
      importance of such physicians to the quality of care at the end of life. DESIGN:
      In 2006 we conducted an exploratory study at a large academic medical center to
      examine the knowledge, attitudes, and practices of hospitalists and residents (n
      = 52, response rate = 85.2%) about the care of terminally ill patients. Data were
      collected using a 22-item survey instrument adapted from previously published
      instruments. RESULTS: Several common myths about treating terminally ill patients
      were identified. These myths pertained to essential aspects of end-of-life care
      including pain and symptom control, indications for various medications, and
      eligibility for hospice. Physicians reported positive attitudes about hospice
      care as well as the belief that many patients who would benefit from hospice do
      not receive hospice at all or only late in the course of their illness.
      CONCLUSIONS: Our findings identified misunderstandings that hospitalists and
      residents commonly have, including about facts essential to know in order to
      provide appropriate pain and symptom management. Future interventions to improve
      knowledge need to focus on specific clinical knowledge about opioid therapy, as
      well as information about eligibility rules for hospice.

PMID- 18080337
TI  - Identification of inpatient DNR status: a safety hazard begging for
      standardization.
AB  - BACKGROUND: Ascertaining and documenting patients' preferences regarding end-of
      life care is required by accrediting organizations at hospital admission.
      However, hospitals vary widely in their methods of making these preferences
      (including do-not-resuscitate [DNR] status) available to frontline providers,
      increasing the potential for errors. METHODS: We surveyed 127 nursing executive
      members of the University HealthSystem Consortium (an alliance of academic
      medical centers), asking them to describe the current practices of their
      hospitals in identifying DNR orders. For those at institutions using color-coded
      wristbands, we also asked about other patient data depicted by wristbands and the
      choice of colors for DNR and these other indications. We used a commercial online
      survey tool with E-mail distribution. RESULTS: Sixty-nine nurse executives
      completed the survey (54%). Fifty-six percent of hospitals use paper
      documentation as their only mode to identify DNR orders, 16% use electronic
      health records, and 25% augment either paper or electronic documentation with a
      color-coded patient wristband. Of those using color-coded wristbands (n = 17), 8
      color schemes were reported. More than 70% of respondents recalled situations
      when confusion around a DNR order led to problems in patient care. CONCLUSIONS:
      Mechanisms to identify DNR orders vary significantly. For hospitals that use
      color-coded wristbands, the variety of color choices poses a risk for confusion
      and error. Building on existing and isolated state initiatives, a national
      mandate to standardize DNR identification and the color of patient wristbands
      would reduce the potential for errors and promote adherence to patients' wishes.

PMID- 18080338
TI  - Perceived health status, alcohol-related problems, and readiness to change among
      medically hospitalized, alcohol-dependent patients.
AB  - OBJECTIVE: Alcohol dependence is prevalent among medically hospitalized patients,
      and acute illness has the potential to increase motivation to change and provide
      a therapeutic window for treatment of alcohol dependence. This study evaluated
      the correlations of readiness to change drinking behavior with perceived physical
      and mental health status and specific alcohol-related consequences of medical
      inpatients. DESIGN AND MEASUREMENTS: The study was a cross-sectional survey of 50
      clinically recognized and subsequently confirmed alcohol-dependent patients
      admitted to general internal medicine teaching services with no evidence of
      chronic cognitive functional deficits. We estimated correlations of process-of
      change variables (problem recognition, ambivalence about change, and taking steps
      to change drinking) with measures of patient perception of general physical and
      mental health status and self-reported alcohol-related consequences. RESULTS:
      Problem recognition (r = -0.31, P = .028) and ambivalence about change (r = 
      0.41, P = .003), but not taking steps to change drinking (r = -0.26, P = .072)
      were significantly associated with perceived physical health. Perceived mental
      health was not associated with these variables, but greater alcohol-specific
      consequences were typically associated with greater recognition, ambivalence, and
      intent to change. CONCLUSIONS: Among alcohol-dependent patients with acute
      medical illness requiring hospitalization, poorer perceived health status was
      associated with increased recognition of drinking problems and thoughts about
      changing drinking behavior. Future research should evaluate if problem
      recognition and ambivalence modify treatment involvement and outcomes following
      hospitalization and if hospital-based interventions designed to link medical
      conditions and their treatment to alcohol dependence enhance recognition and
      ambivalence.

PMID- 18080339
TI  - Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B:
      Results at 1 year of a randomized, double-blind trial.
AB  - Chronic hepatitis B and its life-threatening sequelae are highly prevalent in
      China. There is a need for effective new therapies to suppress hepatitis B virus
      (HBV) replication and ameliorate liver disease. In this study, we compared the
      efficacy of telbivudine, a nucleoside analogue, with lamivudine in Chinese
      patients. In this phase III, double-blind, multicenter trial conducted in China,
      332 patients with compensated hepatitis B e antigen (HBeAg)-positive or HBeAg
      negative chronic hepatitis B were randomly assigned to treatment with 600 mg of
      telbivudine or 100 mg of lamivudine daily for 104 weeks. The primary efficacy
      endpoint was reduction in serum HBV DNA levels at week 52 of treatment. Secondary
      endpoints included clearance of HBV DNA to undetectable levels, HBeAg loss and
      seroconversion, therapeutic response, and alanine aminotransferase (ALT)
      normalization. Viral resistance and safety were assessed. At week 52, among 290
      HBeAg-positive patients, mean reductions of serum HBV DNA were significantly
      greater in telbivudine recipients than lamivudine recipients (6.3 log(10) versus
      5.5 log(10), P < 0.001), and HBV DNA was polymerase chain reaction-negative in
      significantly more telbivudine recipients than lamivudine recipients (67% versus
      38%, P < 0.001). ALT normalization (87% versus 75%, P = 0.007), therapeutic
      response (85% versus 62%, P = 0.001), and HBeAg loss (31% versus 20%, P = 0.047)
      were also significantly more common in the telbivudine group. Treatment effects
      showed similar patterns in the smaller HBeAg-negative group (n = 42). Viral
      resistance in telbivudine recipients was approximately half that observed with
      lamivudine; however, this difference was not statistically significant. Clinical
      adverse events were similar in the two treatment groups. CONCLUSION: In Chinese
      patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided
      greater antiviral and clinical efficacy than lamivudine, with less resistance.

PMID- 18080340
TI  - Monovalent cations and their influence on activated sludge floc chemistry,
      structure, and physical characteristics.
AB  - Multivalent cations have been known to be important components of activated
      sludge floc structure due to their bridging ability of the negatively charged
      sites on the biopolymer network. Recently in batch systems it was found that
      excess concentration of monovalent cations led to the deterioration in
      settleability, dewaterability of sludges and effluent quality of the system. In
      this study, effect of influent monovalent cations (potassium and sodium) on
      activated sludge floc structure was investigated in semi-continuous reactors.
      Results revealed that the increase in concentration of both ions correlated to
      the general increase in total EPS concentration. The zeta potential values were
      affected by the cation type and dose in such a way that sludge from sodium
      reactors had always higher zeta potential values (higher negative charge) than
      the sludges from potassium reactors. Flocs from sodium reactors were more fragile
      and weak and the capillary suction time values of these sludges were higher
      compared to those from potassium reactors. The findings of this research conclude
      that the floc structure is significantly weakened with the increase of monovalent
      cations. Even though EPS is produced, it is unable to bind the floc components
      together. With this, the physical properties of sludge deteriorate for both
      cations.

PMID- 18080341
TI  - Live cells-based cytotoxic sensorchip fabricated in a microfluidic system.
AB  - We report here a live cells-based sensorchip fabricated in microfluidic channels
      in which several laminar flows were achieved. In addition, we established a
      cytotoxic sensor cell line, which was transfected with a green fluorescence
      protein (GFP) plasmid derived from the heat shock protein 70B' (HSP70B')
      promoter, which is induced by cytotoxic reagents. The fluorescence in the sensor
      cells increased in a CdCl(2) dose-dependent manner in the microfluidic channels.
      In this system, cytotoxic reagents can be quantitatively detected in a quick,
      sensitive and high-throughput manner. The combination of sensor cells and
      microfluidic systems will provide an important basis for the development of micro
      total analysis systems (micro-TAS) technology, and can be applied to toxicology,
      environmental assessment and drug screening.

PMID- 18080342
TI  - Effect of solution pH on protein transmission and membrane capacity during virus
      filtration.
AB  - Although virus filtration is now an integral part of the overall viral clearance
      strategy for the purification of many commercial therapeutic proteins, there is
      currently little understanding of the factors controlling the performance of the
      virus filters. The objective of this study was to examine the effects of solution
      pH on protein transmission and capacity during virus filtration. Data were
      obtained using bovine serum albumin as a model protein with Viresolve 180
      membranes oriented with both the skin-side up and skin-side down. Membranes were
      also characterized using dextran sieving measurements both before and after
      protein filtration. Membrane capacity and protein yield were minimal at the
      protein isoelectric point, which was due to the greater degree of concentration
      polarization associated with the smaller protein diffusion coefficient at this
      pH. In contrast, the actual protein sieving coefficient was maximum at the
      protein isoelectric point due to the absence of any strong electrostatic
      exclusion under these conditions. The yield and capacity were both significantly
      greater when the membrane was oriented with the skin-side down. These results
      provide important insights into the effects of solution conditions on the
      performance of virus filtration membranes for protein purification.

PMID- 18080343
TI  - Functionalization of a poly(D,L)lactic acid surface with galactose to improve
      human keratinocyte behavior for artificial epidermis.
AB  - The production of artificial epidermis using reabsorbable polymeric matrices is
      one of possible goals; one of most used strategies in this field is the polymer
      substrate functionalitation using specific growth factors, in order to accelerate
      and improve keratinocyte adhesion and proliferation. In this study films of
      poly(D,L)lactide (P(D,L)LA), have been functionalized with various concentrations
      of galactose (GAL, 1-5-10%, w/v) conjugated with poly-L-lysine (PLL) using 1-etil
      3-(3-diaminopropil) carbodiimide (EDC) as a coupling agent. GAL is a disaccharide
      present in the extracellular matrix (ECM) and it is bind by Galectines, a family
      of cell receptors whose activation regulate the cell-matrix interaction and cell
      growth and apoptosis. One of these receptors, Galectin-7 (Gal-7), is selectively
      expressed by human keratinocytes. Spontaneously immortalized human keratinocytes
      (HaCaT) that express high level of Gal-7 were allowed to adhere for 4 h in serum
      free condition on control P(D,L)LA (PLA), and on PLA-GAL and cell proliferation;
      the production of matrix metalloproteinases (MMP-2, MMP-9, and MMP-28), involved
      in cellular migration and tissue homeostasis have been analyzed after 24 h. The
      presence of GAL onto the polymer surface increased both cell adhesion, spreading
      and proliferation along with MMP-9 and MMP-28 production, suggesting that polymer
      functionalization using GAL could be an useful tool for the production of an
      artificial epidermis.

PMID- 18080344
TI  - Thermodynamic and kinetic characterization using process dynamics: acidophilic
      ferrous iron oxidation by Leptospirillum ferrooxidans.
AB  - Kinetic and stoichiometric properties of acidophilic aerobic ferrous iron
      oxidation by growing and non-growing Leptospirillum ferrooxidans cultures were
      investigated. The use of a continuous stirred tank reactor operated at a variable
      dilution rate and equipped with on-line measurement of the electron donor,
      acceptor and anabolic substrate uptake rate enabled detailed kinetic
      characterization from a single experiment. It was demonstrated that substrate
      conversion and microbial growth are tightly coupled processes in L. ferrooxidans,
      and uncoupling occurs only due to the minor impact of substrate conversion for
      growth-independent maintenance purposes. The tight stoichiometric coupling
      implies bioenergetic uncoupling of the catabolism and anabolism because the Gibbs
      energy change for ferrous iron oxidation as a function of the actual growth rate
      of the culture ranges from -45 to -25 kJ mol-FeII(-1). Bioenergetic description
      of the process could only be achieved by introduction of a growth rate dependent
      Gibbs energy dissipation term. Removal of carbon dioxide from the influent gas
      stopped biomass growth, but the biomass specific respiration rate was unaffected
      or slightly stimulated. The uncoupling of the catabolism and anabolism is
      suggested to induce instantaneously an energy dissipation pathway. Also dosage of
      a low concentration propionic acid resulted in complete inhibition of the
      anabolism. Propionic acid served as an uncoupler of the membrane potential and
      all catabolic energy is required for the increased maintenance requirements.
      Recovery of the anabolism after reestablishment of the normal cultivation
      conditions was obtained only after 1-2 days. The results obtained provide
      additional constraints on cultivation of L. ferrooxidans for biotechnological
      application.

PMID- 18080346
TI  - Effect of electric currents on bacterial detachment and inactivation.
AB  - Since biofilms show strong resistance to conventional disinfectants and
      antimicrobials, control of initial bacterial adhesion is generally accepted as
      one of the most effective strategies for preventing biofilm formation. Although
      electrical methods have been widely studied, the specific properties of cathodic,
      anodic, and block currents that influence the bacterial detachment and
      inactivation remained largely unclear. This study investigated the specific role
      of electric currents in the detachment and inactivation of bacteria adhered to an
      electrode surface. A real-time bacterial adhesion observation and control system
      was employed that consisted of Pseudomonas aeruginosa PAO1 (PAO1) with green
      fluorescent protein as the indicator microorganism and a flow cell reactor
      mounted on a fluorescent microscope. The results suggest that the bacteria that
      remained on the electrode surface after application of a cathodic current were
      alive, although the extent of detachment was significant. In contrast, when an
      anodic current was applied, the bacteria that remained on the surface became
      inactive with time, although bacterial detachment was not significant. Further,
      under these conditions, active bacterial motions were observed, which weakened
      the binding between the electrode surface and bacteria. This phenomenon of
      bacterial motion on the surface can be used to maximize bacterial detachment by
      manipulation of the shear rate. These findings specific for each application of a
      cathodic or anodic electric current could successfully explain the effectiveness
      of block current application in controlling bacterial adhesion.

PMID- 18080345
TI  - Spectrophotometric ferric ion biosensor from Pseudomonas fluorescens culture.
AB  - Pseudomonas fluorescens cultures produce fluorescent siderophores. By utilizing
      optimal conditions for maximizing siderophore production in shake flask cultures
      of P. fluorescens, we report successful characterization of the culture broth
      supernatant as a robust ferric ions biosensor. For characterizing the ferric ions
      biosensor, we tested the effects of pH, buffers, different ferric salts and
      possible interference by ferrous ions under different solution conditions. We
      find that the biosensor is very specific to ferric ions only with sensitivity to
      concentrations as low as 10 microM. Further, the response time of the biosensor
      is the shortest (approximately 5 min or smaller) for citrate as the accompanying
      anion with ferric ions. While the response time is longer than that expected of
      normal biosensors, it is well compensated by the simplicity and economics of the
      biosensor production. Extremely low standard deviations in several experimental
      repeats also highlight the robustness of the ferric ions biosensor. Most
      importantly, the biosensor is extremely easy to use due to its straightforward
      spectrophotometric applications. We also show the utility of the biosensor with
      the high resolution technique of fluorescence microscopy. Finally, we report a
      novel mechanistic finding that siderophores present in the culture broth
      supernatants have two distinct optically active sites on them, which can be
      monitored independently in presence or absence of ferric ions.

PMID- 18080347
TI  - Determination of diffusion coefficients and diffusion characteristics for
      chlorferon and diethylthiophosphate in Ca-alginate gel beads.
AB  - Diffusion characteristics of chlorferon and diethylthiophosphate (DETP) in Ca
      alginate gel beads were studied to assist in designing and operating bioreactor
      systems. Diffusion coefficients for chlorferon and DETP in Ca-alginate gel beads
      determined at conditions suitable for biodegradation studies were 2.70 x 10(-11)
      m(2)/s and 4.28 x 10(-11) m(2)/s, respectively. Diffusivities of chlorferon and
      DETP were influenced by several factors, including viscosity of the bulk
      solution, agitation speed, and the concentrations of diffusing substrate and
      immobilized cells. Diffusion coefficients increased with increasing agitation
      speed, probably due to poor mixing at low speed and some attrition of beads at
      high speeds. Diffusion coefficients also increased with decreasing substrate
      concentration. Increased cell concentration in the gel beads caused lower
      diffusivity. Theoretical models to predict diffusivities as a function of cell
      weight fraction overestimated the effective diffusivities for both chlorferon and
      DETP, but linear relations between effective diffusivity and cell weight fraction
      were derived from experimental data. Calcium-alginate gel beads with radii of
      1.65-1.70 mm used in this study were not subject to diffusional limitations:
      external mass transfer resistances were negligible based on Biot number
      calculations and effectiveness factors indicated that internal mass transfer
      resistance was negligible. Therefore, the degradation rates of chlorferon and
      DETP inside Ca-alginate gel beads were reaction-limited.

PMID- 18080348
TI  - Proceedings of the Eleventh Conference on Cancer Therapy with Antibodies and
      Immunoconjugates. October 12-14, 2006. Parsippany, New Jersey, USA.

PMID- 18080350
TI  - Sexually transmitted diseases and risk behaviors among pregnant women attending
      inner city public sexually transmitted diseases clinics in Baltimore, MD, 1996
      2002.
AB  - OBJECTIVE: To determine the prevalence of sexually transmitted diseases (STDs)
      and characterize behavioral correlates among pregnant women attending inner city
      public STD clinics. STUDY DESIGN: A retrospective study of 2303 pregnant women
      frequency matched by clinic and year of visit to 2303 nonpregnant women seeking
      services during years 1996 to 2002 at public STD clinics in Baltimore, MD.
      RESULTS: On average, 329 pregnant women attended Baltimore City STD clinics each
      year during 1996 to 2002. Forty-six and a half percent of pregnant women knew
      they were pregnant when they presented to the STD clinic. Although pregnant women
      were younger (23.3 vs. 28.3 years of age, P <0.01) and more likely to have sought
      STD clinical services in the past (55.4% vs. 51.5%, P <0.01), they were less
      likely to report high-risk sexual behaviors such as new (4.6% vs. 7.0%, P <0.01)
      or multiple sex partners (11.6% vs. 13.9%, P <0.01) than nonpregnant women.
      However, prevalence of gonorrhea (4.8% pregnant vs. 4.2%), chlamydia (9.9% vs.
      7.7%), trichomoniasis (12.4% vs. 12.0%), and early syphilis (1.5% vs. 1.2%) was
      high, and both groups were equally as likely to have any STD. CONCLUSION: The
      prevalence of STDs was similar for pregnant and nonpregnant women attending the
      inner city public STD clinics, despite differences in risk factors for STDs.
      Understanding the impact of STDs on perinatal outcomes among this population and
      developing targeted interventions to reduce STD-related maternal and infant
      morbidity are critical public health issues.

PMID- 18080349
TI  - Phase I safety trial of two vaginal microbicide gels (Acidform or BufferGel) used
      with a diaphragm compared to KY jelly used with a diaphragm.
AB  - OBJECTIVES: To assess the safety and acceptability of 2 vaginal microbicide gels
      (Acidform and BufferGel) used with a diaphragm compared to KY Jelly used with a
      diaphragm among low-risk, sexually abstinent women. STUDY DESIGN: Eighty-one
      women enrolled in a randomized, masked, phase I safety study using a diaphragm
      with Acidform, BufferGel, or KY Jelly for 6 to 10 hours nightly for 14 nights.
      Physical examination, colposcopy, and lab studies were performed after 1 and 2
      weeks of use. Diaries and questionnaires were used to assess user acceptability.
      RESULTS: Sixty-nine participants (85%) completed the study. Safety and
      acceptability appeared similar among the 3 study groups and no serious adverse
      events related to the study products were reported. Adverse events were mild and
      anticipated. CONCLUSIONS: Acidform and BufferGel compared to KY Jelly, when used
      with diaphragm daily for 14 days, appeared to be safe and acceptable in a small
      study of low-risk abstinent women.

PMID- 18080351
TI  - Assessment of adherence to product dosing in a pilot microbicide study.
AB  - OBJECTIVES: To determine whether applicator staining could be incorporated into a
      microbicide study as a marker of adherence. GOAL: To test whether observers could
      identify intravaginally inserted applicators and compare the observers' ratings
      to subjects' self reports. STUDY DESIGN: Subjects participating in a 14-day
      microbicide trial to assess the safety of 0.5% PRO 2000 or matched placebo gel
      returned used and unused applicators. Each applicator was individually dyed or
      batched and immersed in a 0.4% trypan blue waterbath. Masked observers rated the
      applicators as intravaginally inserted or not; results were compared to subjects'
      self-reports. To determine if the dye would allow observers to differentiate
      whether applicators had been filled before intravaginal insertion, staff either
      filled applicators and discarded gel ex vivo or asked volunteers to
      intravaginally insert applicators without gel and mixed these with a random
      sampling of used and unused study samples. RESULTS: 358 of 360 applicators were
      returned; 306 were reported to have been vaginally inserted and 52 unused.
      Observers agreed with the participant's self reports in 98-99% of cases. No
      differences were observed between applicators stained individually or in batches.
      The ability to distinguish between applicators that were presumed to have been
      used properly, intravaginally inserted without gel, filled with gel and emptied
      ex vivo, or unused ranged from 76 to 87%. CONCLUSIONS: Staining of applicators is
      accurate, inexpensive, and correlated well with self-report in a study of short
      duration. This method could prove useful in assessing adherence to product dosing
      in future microbicide trials.

PMID- 18080352
TI  - An evaluation of the relative sensitivities of the venereal disease research
      laboratory test and the Treponema pallidum particle agglutination test among
      patients diagnosed with primary syphilis.
AB  - BACKGROUND: Because definitive methods for diagnosing primary syphilis are
      limited, it is important to optimize the sensitivity of serodiagnosis. OBJECTIVE:
      To determine the most sensitive testing approach to the diagnosis of primary
      syphilis, using the commonly available serologic tests: the Venereal Disease
      Research Laboratory (VDRL) test and the Treponema pallidum particle agglutination
      (TP-PA) test. METHODS: Sensitivities of 2 serologic testing strategies for
      primary syphilis were compared among 106 darkfield-confirmed cases treated in San
      Francisco from January 2002 through December 2004. RESULTS: The sensitivity of
      the diagnostic strategy using VDRL confirmed by TP-PA was 71% (95% CI, 61%-79%).
      Substituting Rapid Plasma Reagin test for VDRL in a subset of 51 patients
      produced the same sensitivity (71%; 95% CI, 56%-83%). The sensitivity of TP-PA as
      the first-line diagnostic test was 86% (95% CI, 78%-92%). The sensitivity of the
      former approach was significantly lower among HIV-positive patients, compared
      with HIV-negative patients (55% vs. 77%, P = 0.05). CONCLUSIONS: The TP-PA test
      as the first-line diagnostic test yielded higher sensitivity for primary syphilis
      than did the use of the currently recommended strategy.

PMID- 18080354
TI  - Proceedings of the First International Workshop on Double Balloon Enteroscopy,
      August, 2006. Tokyo, Japan.

PMID- 18080355
TI  - Proceedings of the Third Croatian Congress on Psychopharmacotherapy. September 26
      27, 2007. Sibenik, Croatia.

PMID- 18080353
TI  - Type-specific seroprevalence of herpes simplex virus type 2 and associated risk
      factors in middle-aged women from 6 countries: the IARC multicentric study.
AB  - GOAL: To determine type-specific seroprevalence of herpes simplex viruses (HSV-1
      and HSV-2) and HSV-2 risk factors. STUDY DESIGN: Six-hundred fifty eight middle
      aged control women (hospital-based in 4 of 6 countries) from a multicenter
      cervical cancer case-control study participated from 1985 to 1997. Type-specific
      serum IgG antibodies against HSV-1 and HSV-2 were detected with Western Blot.
      RESULTS: HSV-1 seroprevalence was 89% to 100% everywhere except Thailand (51%).
      HSV-2 seroprevalence ranged from 9% (Spain) to 57% (Colombia), and was
      independently associated with having >or=2 lifetime sexual partners overall [Odds
      ratio (OR), 2.1; 95% confidence interval (CI) 2.5-3.1], and in Morocco (OR, 2.7;
      95% CI, 1.2-6.1) and Thailand (OR, 4.4; 95% CI, 1.3-15.4), and with being
      unmarried in Colombia, Peru, Spain, but not significantly in Mali. Women whose
      male partner's sexual debut was <or=17 years had a higher HSV-2 risk (OR, 4.3 95%
      CI, 1.3-13.7). CONCLUSIONS: HSV-2 seroprevalence in middle-aged women varied over
      4-fold and was associated with riskier sexual behaviors in women and their male
      partners.

PMID- 18080356
TI  - Recent advances in asthma research. Proceedings of an international symposium.
      November 19-22, 2006. Deep Bay, St. John's, Antigua.

PMID- 18080357
TI  - Sexually transmitted diseases and risk behaviors among market vendors in China.
AB  - OBJECTIVES: The rate of sexually transmitted diseases (STDs) in China has soared
      over the past 20 years. There is a need to study STD prevalence in the general
      population of the country. GOAL: To report the prevalence and patterns of STDs
      and the relationships between STD status and demographic and behavioral factors.
      STUDY DESIGN: A total of 4,510 market vendors in a city in eastern China were
      interviewed and tested for STDs. RESULTS: The prevalence of any STD among
      participants was 16.55% (women, 21.04%; men, 11.54%). Among those who tested
      positive for an STD, chlamydia was most common (8.89%), followed by herpes
      (6.50%). Participants who had no schooling and participants who had college or
      higher level of schooling had a similarly high STD prevalence (26.19% vs. 24.00%,
      respectively). Prevalence of all STDs was significantly higher among women, those
      with more discretionary income, and those with multiple partners. CONCLUSIONS:
      Special considerations are needed for low versus high education groups as well as
      men versus women to maximize the effects of STD prevention programs and messages
      in China.

PMID- 18080358
TI  - Renin-angiotensin system blockade: therapeutic implications beyond blood pressure
      control.

PMID- 18080359
TI  - A case-control study to estimate the impact of the Icelandic population-based
      mammography screening program on breast cancer death.
AB  - BACKGROUND: The Icelandic breast cancer screening program, initiated November
      1987 in Reykjavik and covering the whole country from December 1989, comprises
      biennial invitation to mammography for women aged 40-69 years old. PURPOSE: To
      estimate the impact of mammography service screening in Iceland on deaths from
      breast cancer. MATERIAL AND METHODS: Cases were deaths from breast cancer from
      1990 onwards in women aged 40 and over at diagnosis, during the period November
      1987 to December 31, 2002. Age- and screening-area-matched, population-based
      controls were women who had also been invited to screening but were alive at the
      time their case died. RESULTS: Using conditional logistic regression on the data
      from 226 cases and 902 controls, the odds ratio for the risk of death from breast
      cancer in those attending at least one screen compared to those never screened
      was 0.59 (95% CI 0.41-0.84). After adjustment for healthy-volunteer bias and
      screening-opportunity bias, the odds ratio was 0.65 (95% CI 0.39-1.09).
      CONCLUSION: These results indicate a 35-40% reduction in breast cancer deaths by
      attending the Icelandic breast cancer screening program. These results are
      consistent with the overall evidence from other observational evaluations of
      mammography-based programs.

PMID- 18080360
TI  - Determination of a confirmation interval for %CDT TIA analysis.

PMID- 18080362
TI  - Aneurysm clip.

PMID- 18080363
TI  - Resident duty hours and professionalism--limits and opportunities.

PMID- 18080364
TI  - Bioethics and armed conflict.

PMID- 18080365
TI  - [What is in the guidelines].

PMID- 18080366
TI  - [Normal breathing or moist rattle sound?].

PMID- 18080367
TI  - [Chronic pruritus in old age].

PMID- 18080368
TI  - [Palliative measures in lung cancer].
AB  - A patient in the final stages of lung cancer primarily needs effective pain
      management, treatment of symptoms such as coughing, breathing difficulty, fatigue
      and if necessary, relief through anti-metastasis therapy when a curative therapy
      is no longer useful. After all best possible medical measures have been employed,
      the final tasks of the family physician include speaking and listening to the
      patient, ideally without time pressure, and providing supportive information for
      the patient and his family.

PMID- 18080369
TI  - [Emergency checklist: acute cholecystitis].

PMID- 18080370
TI  - [Blood sugar adjustment -- a large improvement potential].

PMID- 18080371
TI  - [Imaging of paranasal sinuses today].
AB  - CT is accepted as the gold standard for pathological-anatomical evaluation of
      paranasal sinus disease, CT is especially considered an obligatory part of
      planning surgical procedures. Indications for paranasal sinus CT include trauma,
      malignant disease, and chronic sinusitis, which accounts for the major part of
      examinations. Due to the benign character of the disease and the relatively
      moderate age of the patients involved, the radiation dose of paranasal sinus CT
      plays an important role. The use of a low-dose spiral CT technique and the
      reformation of coronal images out of the axial CT data instead of an additional
      direct coronal scan allow the effective dose of paranasal sinus CT to be reduced
      to the order of a chest radiogram. MRI is the preferred imaging modality in
      malignant disease or complications of inflammatory sinus disease that extend
      beyond the limits of the paranasal sinuses. The clinical value of other imaging
      modalities, including plain film radiography, ultrasound, or scintigraphy, is
      limited to special indications.

PMID- 18080372
TI  - [Treatment of midfacial fractures].
AB  - Fractures of the midface constitute half of all traumas involving facial bones.
      Computed tomography is very useful in primary diagnosis. Isolated fractures of
      the nasal bone and lateral midfacial structures may be diagnosed sufficiently by
      conventional x-rays. An exact description of the fracture lines along the
      midfacial buttresses is essential for treatment planning. For good aesthetics and
      function these have to be reconstructed accurately, which can be checked with x
      rays. The treatment of midfacial fractures has been revolutionized over the last
      two decades. A stabile three-dimensional reconstruction of the facial shape is
      now possible and the duration of treatment has shortened remarkably. The
      frequently occurring isolated fractures in the lateral part of the midface may be
      treated easily and effectively by semi-surgical methods such as the Gillies
      procedure or hook-repositioning.

PMID- 18080373
TI  - [Imaging in inflammatory diseases of the paranasal sinuses].
AB  - The goals of imaging in inflammatory disease of the paranasal sinuses are
      confirmation of the diagnosis, evaluation of the extent of the disease, and
      description of the different anatomic variants in order to select the patients
      who would benefit from surgical treatment of paranasal sinus disease. The most
      common inflammatory changes of the paranasal sinuses, the complications of
      inflammatory disease, and the optimal imaging strategy are presented.

PMID- 18080374
TI  - Too many rules can make an office less than patient friendly.

PMID- 18080375
TI  - Avoiding harassment and discrimination as an optometric employer.

PMID- 18080376
TI  - Biosecurity, livestock health and the livestock producer.

PMID- 18080377
TI  - Exotic Animal Diseases Bulletin. Australian Bat Lyssavirus(ABLV).

PMID- 18080378
TI  - [Primary splenic lymphoma and hepatitis B virus].

PMID- 18080379
TI  - [Bite of a poisonous snake].

PMID- 18080380
TI  - [Anemia and abdominal mass in a 15-years old patient].

PMID- 18080381
TI  - [Tetraparesis secondary to paravertebral tumour].

PMID- 18080382
TI  - [Occult bronchial foreign body aspiration].

PMID- 18080383
TI  - [Analysis of 7 years from liver transplantation programme].

PMID- 18080384
TI  - Epoetin alfa in critically ill patients.

PMID- 18080385
TI  - Low-tidal-volume ventilation.

PMID- 18080386
TI  - Spiraling instrument costs present many challenges.

PMID- 18080387
TI  - State policies to support adolescents.

PMID- 18080388
TI  - On lawful concubinage in Athens.

PMID- 18080389
TI  - Amor, ira, and sexual identity in Ovid's Metamorphoses.

PMID- 18080390
TI  - Cooks in Plautus.

PMID- 18080391
TI  - Hearing assistive technology considerations for older individuals with dual
      sensory loss.
AB  - This article focuses on the current state of the science related to audiologic
      rehabilitation of individuals with dual sensory impairment, with an emphasis on
      considerations for provision of appropriate hearing assistive technology for this
      population. A substantial increase in the number of older adults is predicted in
      the coming years, many of whom will have significant age-related impairments in
      hearing and vision. Thus, hearing care professionals will be called on
      increasingly to attend to the special needs of people with dual sensory
      impairments to ensure maximal quality of life and independence for these
      individuals. Access to sound is critical for individuals who live with
      compromises in both vision and hearing. Hearing assistive technology may improve
      not only their speech perception but also their connection and orientation to the
      environment, as well as enable greater mobility. Thus, the audiologist's
      provision of appropriate and carefully selected hearing assistive technology may
      contribute dramatically to the quality of life of the individual with dual
      sensory loss. Prefitting, fitting, and postfitting considerations in providing
      hearing aids and other assistive technology to individuals with dual sensory
      impairment are reviewed.

PMID- 18080392
TI  - "Cool" new treatment: NFL uses hypothermia for spinal cord injury.

PMID- 18080393
TI  - Ariadne and others: images of sleep in Greek and Early Roman art.

PMID- 18080394
TI  - Conflicts of interest:  avoid the appearance of impropriety.

PMID- 18080395
TI  - 2008 Buyer's Guide.

PMID- 18080396
TI  - Hands on: product reviews from street crews.

PMID- 18080397
TI  - The role of the plague in the Iliad.

PMID- 18080398
TI  - Slouching towards Boeotia: age and age-grading in the Hesiodic myth of the five
      races.

PMID- 18080400
TI  - Medea's divided self.

PMID- 18080399
TI  - Maraviroc (Celsentri) for multidrug-resistant human immunodeficiency virus (HIV)
      1.
AB  - (1) Maraviroc belongs to a new class of antiretroviral drugs designed to block
      entry of HIV-1 into CD4+ T-cells via the CCR5 coreceptor. It is indicated for
      combination therapy in treatment-experienced adults infected with CCR5-tropic HIV
      1 that is resistant to multiple antiretroviral agents. (2) Results from two
      randomized controlled trials (RCTs) indicate that in treatment experienced
      patients, maraviroc, combined with optimized background therapy (OBT),
      significantly decreases the level of HIV-1 RNA in the blood (viral load) when
      compared with OBT alone. The number of patients achieving undetectable viral
      loads and CD4+ cell count increases were also significantly higher in those
      receiving maraviroc. (3) Most patients experiencing treatment failure with
      maraviroc exhibit tropism changes from CCR5-tropic to CXCR4-using virus, but
      there is no evidence of disease progression. (4) Adverse effects reported with
      maraviroc include cough, fever, upper respiratory tract infections, rash, muscle
      and joint pain, abdominal pain, and postural hypotension (dizziness). No
      significant increases in cardiovascular events, hepatotoxicity, infections or
      malignancies have been reported with short-term maraviroc therapy. Several post
      marketing studies will assess maraviroc's long-term safety for immune function,
      liver function, malignancy, cardiac events, and risks associated with changes in
      tropism. (5) Results from an ongoing trial in treatment naive patients suggest
      that maraviroc may not be superior in terms of viral suppression to standard
      therapy, but may significantly increase the number of CD4+ T-cells.

PMID- 18080401
TI  - Attitudes toward death in Archaic Greece.

PMID- 18080402
TI  - Those Athenian bastards.

PMID- 18080403
TI  - Special report: pharmacogenomics of cancer-candidate genes.

PMID- 18080404
TI  - The sign of the fall: the scars of Orestes and Odysseus.

PMID- 18080405
TI  - Scripts and themes: cognitive research and the Homeric epic.

PMID- 18080406
TI  - Epidermal growth factor receptor mutations and tyrosine kinase inhibitor therapy
      in advanced non-small-cell lung cancer.

PMID- 18080408
TI  - Special report: cardiovascular pharmacogenomics.

PMID- 18080407
TI  - Maternity and mortality in Homeric poetry.

PMID- 18080409
TI  - Achilles heel: the death of Achilles in ancient myth.

PMID- 18080410
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) protocols. Preface.

PMID- 18080411
TI  - Guest Editorial: A note on the notion of commercialism.

PMID- 18080412
TI  - Pattern recognition by B cells: the role of antigen repetitiveness versus Toll
      like receptors.
AB  - Viruses induce excellent antibody responses due to several intrinsic features.
      Their repetitive, organised structure is optimal for the activation of the B cell
      receptor (BCR), leading to an increased humoral response and a decreased
      dependence on T cell help. Viruses also trigger Toll-like receptors (TLRs), which
      in addition to increasing overall Ig levels, drive the switch to the IgG2a
      isotype. This isotype is more efficient in viral and bacterial clearance and will
      activate complement, which in turn lowers the threshold of BCR activation.
      Exploiting these characteristics in vaccine design may help us to create vaccines
      which are as safe as a recombinant vaccine yet still as effective as a virus in
      inducing B cell responses.

PMID- 18080413
TI  - The multifunctional role of antibodies in the protective response to bacterial T
      cell-independent antigens.
AB  - While most complex antigens can induce antibody responses in a mature
      immunological system, this is not the case when injected into ontogenetically
      immature systems, as are found in neonates and pediatric-age children. Thus the
      antibody response to polysaccharides, which would in theory provide protection
      against infection by all polysaccharide encapsulated bacteria, including
      Streptococcus pneumoniae, Neisseria meningitides, and Haemophilus influenzae,
      cannot be stimulated by immunization with the polysaccharides by themselves. It
      was only with the introduction of conjugate vaccines that protection from these
      bacterial infections was provided to this susceptible age group. The introduction
      of these conjugate vaccines into the arsenal of vaccines serves as a remarkable
      example of how valuable it is to understand the mechanisms of biological
      processes. Many years of intense laboratory investigation demonstrated that when
      polysaccharides are covalently conjugated to proteins, the characteristics of the
      immune response are similar to that of the protein rather than the
      polysaccharide. These characteristics would induce an anti-polysaccharide
      response even in the pediatric population, which was heretofore unable to mount
      protective responses to the polysaccharide. With the advent of conjugate vaccines
      for the above three mentioned bacteria, the incidence of bacteremia, meningitis,
      and otitis media has almost been eliminated. This chapter discusses in some
      detail the mechanisms which underlie the effectiveness of conjugate vaccines and
      discusses some of the vaccines that have been commercialized.

PMID- 18080414
TI  - B cell lineage contributions to antiviral host responses.
AB  - B cell responses are a major immune protective mechanism induced against a large
      variety of pathogens. Technical advances over the last decade, particularly in
      the isolation and characterization of B cell subsets by multicolor flow
      cytometry, have demonstrated the multifaceted nature of pathogen-induced B cell
      responses. In addition to participation by the major follicular B cell
      population, three B cell subsets are now recognized as key contributors to
      pathogen-induced host defenses: marginal zone (MZ) B cells, B-1a and B-1b cells.
      Each of these subsets seems to require unique activation signals and to react
      with distinct response patterns. Here we provide a brief review of the main
      developmental and functional features of these B cell subsets. Furthermore, we
      outline our current understanding of how each subset contributes to the humoral
      response to influenza virus infection and what regulates their differential
      responses. Understanding of the multilayered nature of the humoral responses to
      infectious agents and the complex innate immune signals that shape pathogen
      specific humoral responses are likely at the heart of enhancing our ability to
      induce appropriate and long-lasting humoral responses for prophylaxis and
      therapy.

PMID- 18080415
TI  - The important and diverse roles of antibodies in the host response to Borrelia
      infections.
AB  - Antibodies are of critical importance in the host response to tick-borne Borrelia
      species that cause relapsing fever and Lyme disease. Recent studies on the role
      of various B cell subsets in the host response to Borrelia, complement
      independent, bactericidal antibodies, and diagnostics led to this review that
      focuses on the array of functions that antibodies to Borrelia can perform.

PMID- 18080416
TI  - A distinct role for B1b lymphocytes in T cell-independent immunity.
AB  - Pathogenesis of infectious disease is not only determined by the virulence of the
      microbe but also by the immune status of the host. Vaccination is the most
      effective means to control infectious diseases. A hallmark of the adaptive immune
      system is the generation of B cell memory, which provides a long-lasting
      protective antibody response that is central to the concept of vaccination.
      Recent studies revealed a distinct function for B1b lymphocytes, a minor subset
      of mature B cells that closely resembles that of memory B cells in a number of
      aspects. In contrast to the development of conventional B cell memory, which
      requires the formation of germinal centers and T cells, the development of B1b
      cell-mediated long-lasting antibody responses occurs independent of T cell help.
      T cell-independent (TI) antigens are important virulence factors expressed by a
      number of bacterial pathogens, including those associated with biological
      threats. TI antigens cannot be processed and presented to T cells and therefore
      are known to possess restricted T cell-dependent (TD) immunogenicity.
      Nevertheless, specific recognition of TI antigens by B1b cells and the highly
      protective antibody responses mounted by them clearly indicate a crucial role for
      this subset of B cells. Understanding the mechanisms of long-term immunity
      conferred by B1b cells may lead to improved vaccine efficacy for a variety of TI
      antigens.

PMID- 18080417
TI  - Secretory immunity following mutans streptococcal infection or immunization.
AB  - Salivary IgA antibody responses to mutans streptococci can be observed in early
      childhood, sometimes even before permanent colonization of the oral biofilm
      occurs. Many of these early immune responses are directed to components thought
      to be essential for establishment and emergence of mutans streptococci in the
      oral biofilm. Initial responses are likely to be modulated by antigen dose, by
      immunological maturity, and by previous encounters with similar antigenic
      epitopes in the pioneer commensal flora. Our understanding of these modulating
      factors is modest and is an opportunity for continued investigation. Under
      controlled conditions of infection, experimental vaccine approaches have
      repeatedly shown that infection and disease can be modified in the presence of
      elevated levels of antibody in the oral cavity. Protection can be observed
      regardless of antibody isotype or method used to actively or passively provide
      the immune reagent. Limited clinical trials have supported the utility of both of
      these approaches in humans. Refinements in antigen formulation, delivery
      vehicles, enhancing agents and routes of application, coupled with approaches
      that are timed to intercept most vulnerable periods of infection of primary and
      permanent dentition may well provide the healthcare practitioner with an
      additional tool to maintain oral health.

PMID- 18080418
TI  - [Advances in the field of osteoporosis].

PMID- 18080419
TI  - [Pulmonary MALT lymphoma].

PMID- 18080420
TI  - [Immunologic deficiencies. Optimizing diagnostic and therapeutic approaches].

PMID- 18080422
TI  - [International classification of primary immunologic deficiencies].

PMID- 18080421
TI  - [Immunity and defenses against infection].
AB  - The roles of the immune system are to protect the host from the various
      pathogenic agents and to ensure the tolerance to self. It brings into play two
      categories of processes which appeared successively during the evolution, innate
      immunity and adaptive immunity. The actors of these two processes will be
      recruited in a sequential way in the event of infection by a micro-organism.

PMID- 18080423
TI  - [Infectious complications of immune deficiencies].
AB  - Infections constitute the most common and severe complication of immune
      deficiencies. The pattern of infections is strikingly dependent on the type of
      immune defect. Antibody deficiencies usually manifest with recurrent capsulated
      bacteria related-infections of the respiratory tract, due to pneumoccoci and
      Haemophilus influenza. The same bacteria are implicated in asplenic patients with
      frequent sepsis of devastating consequences. Complement deficiencies must be
      looked for in case of meningococcal infections. Neutropenia and defects in
      phagocytic cell functions favour bacteraemia and invasive fungal infections.
      Importantly, neutropenia can rapidly lead to septic shock. Cellular immune
      deficiencies are associated with opportunistic infections including viral
      infections due to Herpes viridae, fungal and parasitic infections (Pneumocystis
      jiroveci, Toxoplasma gondii) and mycobacterial infections. Most of the time,
      immune defects are combined, accounting for the variety and the complexity of
      clinical presentations and microbial investigations.

PMID- 18080425
TI  - [How to diagnose a hereditary immunodeficiency?].
AB  - Efficient early identification of primary immunodeficiency is important for the
      patient prognosis and treatment. The first investigations need to be performed in
      case of severe, recurrent and/or unusual infections. Simple investigations like
      blood cell count, serum immunoglobulins level and postvaccination or post
      infection serologies allow to direct the diagnosis. The medical history, the
      clinical examination and these laboratory investigations permit to realize more
      specific investigations according to the type of primary immunodeficiency
      suspected.

PMID- 18080424
TI  - [When to suspect immunologic deficiency?].
AB  - Symptoms and signs that point to immunodeficiency are numerous and various.
      Recurrent history, unusual pathogens or severe course of infections should alert
      any physician to potential immunodeficiency state. If infections are the hallmark
      of immunodeficiency, other manifestations such as autoimmune diseases or
      particular malignancies can be a presenting feature of immunodeficiency. If many
      primary or secondary immunodeficiencies are well defined, it is important for the
      general practitioners to know that a large number of underlying conditions can
      lead to immunodeficiency states.

PMID- 18080426
TI  - [Infectious complications due to immunosuppression in organ transplant patients].
AB  - Prevention and treatment of allograft rejection by immunosuppressive treatments
      expose organ transplant patients to frequent and sometimes severe infectious
      complications. Immunosuppressive drugs inhibit both the immune response to
      alloantigens, and the anti-infectious immunity; they promote intracellular
      infections, including infections with viruses and with bacterial, parasitic and
      mycotic agents. Infectious risks are related to duration of immunosuppression
      exposure, type of immunosuppressive drugs, combination of drugs and trough levels
      required to control rejection. Assessment of the risk of infectious diseases in
      transplant patients before transplantation has to take into account past medical
      history, number of previous transplantations, immunosuppressive regimen, and the
      risk of infectious diseases transmitted from the donor. After the graft,
      infectious risks have to be assessed by clinical examination, repeated white
      blood cell count to detect leucopenia. In high risk population, monitoring for
      CMV and EBV infections is based on analysis of replication using nucleic acid
      based assays or antigenemia studies. Prophylactic anti-infectious therapy in high
      risk patients has resulted in reduction of the consequences of
      overimmunosuppression in organ transplantation.

PMID- 18080427
TI  - [Common variable immunodeficiency].
AB  - Common variable immunodeficiency (CVID) is the most frequent primary
      immunodeficiency in adults. It is characterized by severe hypogammaglobulinemia.
      Males and females are equally affected. The prevalence of the disease in France
      is probably arround 1/25,000; however CVID is rare in people from Asian ancestry
      and almost absent in Blacks. The deficit is familial in 20-25% of the cases.
      Clinical onset is usually during the third decade of life but may also concern
      children or seniors. Delay for diagnosis often remains of several years. Upper
      respiratory tract infections are the most frequent complications of CVID (> 85%)
      and may lead to severe bronchiectasis. Gastrointestinal and liver disease,
      autoimmune cytopenia, splenomegaly and lymphoproliferative disease may also
      complicate CVID. A specific genetic defect can be demonstrated in less than 5% of
      the cases. Therapy relies on IV or SC substitution using polyvalent
      immunoglobulins.

PMID- 18080428
TI  - [Immunoglobulin therapy of primary humoral immunologic deficiencies].
AB  - There is a strong body of evidence documenting that immunoglobulin therapy
      reduces the incidence and severity of infections in patients with primary humoral
      immunodeficiencies, whatever patient's age. Health-related quality of life is
      significantly improved in particular by self-infusions of subcutaneous
      immunoglobulins. Residual levels of total IgG over 6-800 mg/dL may help prevent
      progression of lung damage. Levels of IgG, clinical manifestations, pulmonary
      function tests and high resolution computed tomography routine surveillance is
      recommended.

PMID- 18080429
TI  - [Curing a congenital immunologic deficiency].

PMID- 18080430
TI  - [Patient handout. Common variable immunodeficiency].

PMID- 18080431
TI  - [Time for reading and the Ingelfinger rule].

PMID- 18080432
TI  - [National ranking exam N52. What could fall out at the exam?].

PMID- 18080433
TI  - [Diagnosis of Raynaud's phenomenon].

PMID- 18080434
TI  - [Diagnosis of urinary incontinence in the adult].

PMID- 18080435
TI  - [Diagnosis of acute diarrhea in the child and in the adult (with treatment). Part
      2--Diagnosis of acute diarrhea in the infant (with treatment)].

PMID- 18080436
TI  - [Psychopathological bases of medical psychology].

PMID- 18080437
TI  - [The adventure of Medicophone].

PMID- 18080438
TI  - Why is the topic of cancer and pregnancy so important? Why and how to read this
      book.

PMID- 18080439
TI  - Prenatal irradiation and pregnancy: the effects of diagnostic imaging and
      radiation therapy.

PMID- 18080440
TI  - Maternal and fetal effects of systemic therapy in the pregnant woman with cancer.

PMID- 18080441
TI  - Breast cancer during pregnancy: epidemiology, surgical treatment, and staging.

PMID- 18080442
TI  - Breast cancer during pregnancy: medical therapy and prognosis.

PMID- 18080443
TI  - Subsequent pregnancy after breast cancer.

PMID- 18080444
TI  - Cervical and endometrial cancer during pregnancy.

PMID- 18080445
TI  - Ovarian cancers in pregnancy.

PMID- 18080446
TI  - Fertility after the treatment of gynecologic tumors.
AB  - In a young woman with gynecologic cancer, preservation of fertility is possible.
      Fertility-sparing surgery may be safe in early ovarian cancer of certain
      histological subtypes such as ovarian tumors of low malignant potential,
      malignant ovarian germ cell tumors, and ovarian sex cord stromal tumors. For
      women with invasive epithelial ovarian cancer who have early-stage disease,
      fertility-sparing surgery may be an option. In some cases, fertility-sparing
      surgery may be followed by postoperative chemotherapy. The concept of fertility
      preserving surgery in early cervical cancer has been adopted by several leading
      centers worldwide as an option for stage Ia and small Ib disease without the
      presence of lymphovascular involvement. Nonsurgical options such as hormonal
      therapy may be considered for women with early-stage, low-grade endometrial
      cancer. Improvements in cancer cure rates and the development of conservative
      treatments mean that many young women with early gynecologic cancer can hope to
      start a new pregnancy after the treatment. Patients are generally advised to wait
      2 years after treatment for any malignancy before attempting pregnancy, but the
      optimal interval between cure and conception must be carefully determined by a
      multidisciplinary team including oncologist and obstetrician. Gynecologic surgery
      and hemotherapy can have an impact not only on fertility, but also on the course
      of a next pregnancy (increased risk of miscarriage and premature delivery, etc.)
      These risks must be taken into account by the obstetrician. Management of young
      women diagnosed with gynecologic cancer should be individualized, with the risk
      of conservative therapy balanced against the disadvantages of more radical
      treatment. The patient and the family should be extensively counseled. The
      alternatives to the traditional and standard radical procedures should be
      discussed, and the limitation of data regarding many conservative treatment
      options should be explained. The patients should be aware that by accepting
      fertility-sparing treatment they are assuming a small but undefined risk for
      recurrence of the disease. They need to know that these conservative therapeutic
      approaches are yet not considered "standard." Furthermore, patients need to be
      assessed for the realistic probabilities of achieving conception on the basis on
      their age, history, and infertility evaluation. Some of them will require
      assisted reproduction technology (ARTS) to help achieve a pregnancy, especially
      in vitro fertilization (IVF). They may also consider ovarian tissue, oocyte, or
      embryo cryopreservation before definitive cancer therapies. And, finally,
      patients also need to understand the risk of premature delivery and the
      consequences of prematurity. The care of the young patient with gynecologic
      malignancy is extremely complex and challenging. It necessarily requires a
      multidisciplinary approach with the close collaboration of gynecologist
      oncologist, reproductive endocrinologist, and perinatologist.

PMID- 18080447
TI  - Leukaemia and pregnancy.
AB  - In summary, the management of women diagnosed with leukaemia in pregnancy needs
      an interdisciplinary approach, including a careful oncological work-up as well as
      close monitoring of the pregnancy until delivery and beyond. Patients with acute
      leukaemias normally must receive anti-leukaemic treatment at full dosage prior to
      delivery, except for selected women diagnosed very close to term. Treatment
      should be avoided in the first trimester. The prognosis of pregnant women with
      acute leukaemia corresponds to that of an age-matched and diagnosis-matched non
      pregnant cohort of patients, provided appropriate treatment is given. If given as
      of the second trimester, the typical chemotherapy regimes used for acute
      leukaemias imply acceptable acute toxicities to the fetus, with a somewhat
      increased risk of premature birth or developmental retardation, but no clear
      evidence of late sequelae in children and adolescents who were exposed to
      cytostatic agents whilst in utero. In chronic leukaemias and MDS, treatment may
      often be delayed until after delivery. In CML targeted therapy with imatinib
      mesylate is safe as of the second trimester, and possibly even before. Obstetric
      care and monitoring of women with leukaemia are essential throughout the
      pregnancy to ensure the best possible outcome for mother and child.

PMID- 18080448
TI  - Hodgkin and non-Hodgkin lymphomas during pregnancy.

PMID- 18080449
TI  - Pregnancy and thyroid cancer.

PMID- 18080450
TI  - Gastrointestinal, urologic and lung malignancies during pregnancy.

PMID- 18080451
TI  - Melanoma during pregnancy: epidemiology, diagnosis, staging, clinical picture.

PMID- 18080452
TI  - Melanoma during pregnancy: therapeutic management and outcome.

PMID- 18080453
TI  - Metastatic involvement of placenta and foetus in pregnant women with cancer.

PMID- 18080454
TI  - The obstetric care of the pregnant woman with cancer.

PMID- 18080455
TI  - Fertility issues and options in young women with cancer.

PMID- 18080456
TI  - Psychooncologic care in young women facing cancer and pregnancy.

PMID- 18080457
TI  - Counseling young cancer patients about reproductive issues.

PMID- 18080458
TI  - Psychosocial issues in young women facing cancer and pregnancy: the role of
      patient advocacy.

PMID- 18080459
TI  - Long-term ex situ conservation of biological resources and the role of biological
      resource centers.
AB  - The establishment and maintenance of biological resource centers (BRCs) requires
      careful attention to implementation of reliable preservation technologies and
      appropriate quality control to ensure that recovered cultures and other
      biological materials perform in the same way as the originally isolated culture
      or material. There are many types of BRC that vary both in the kinds of material
      they hold and in the purposes for which the materials are provided. All BRCs are
      expected to provide materials and information of an appropriate quality for their
      application and work to standards relevant to those applications. There are
      important industrial, biomedical, and conservation issues that can only be
      addressed through effective and efficient operation of BRCs in the long- term.
      This requires a high degree of expertise in the maintenance and management of
      collections of biological materials at ultra-low temperatures, or as freeze-dried
      material, to secure their long-term integrity and relevance for future research,
      development, and conservation.

PMID- 18080460
TI  - The principles of freeze-drying.
AB  - This chapter provides an up-to-date overview of freeze-drying (lyophilization)
      with particulars relevance to stabilizing live cells or viruses for industrial
      applications as vaccines or seed culture. The chapter discusses the importance of
      formulation, cycle development, validation, and the need to satisfy
      pharmaceutical regulatory requirements necessary for the commercial exploitation
      of freeze-dried products.

PMID- 18080461
TI  - Principles of cryopreservation.
AB  - Cryopreservation is the use of very low temperatures to preserve structurally
      intact living cells and tissues. Unprotected freezing is normally lethal and this
      chapter seeks to analyze some of the mechanisms involved and to show how cooling
      can be used to produce stable conditions that preserve life. The biological
      effects of cooling are dominated by the freezing of water, which results in the
      concentration of the solutes that are dissolved in the remaining liquid phase.
      Rival theories of freezing injury have envisaged either that ice crystals pierce
      or tease apart the cells, destroying them by direct mechanical action, or that
      damage is from secondary effects via changes in the composition of the liquid
      phase. Cryoprotectants, simply by increasing the total concentration of all
      solutes in the system, reduce the amount of ice formed at any given temperature;
      but to be biologically acceptable they must be able to penetrate into the cells
      and have low toxicity. Many compounds have such properties, including glycerol,
      dimethyl sulfoxide, ethanediol, and propanediol. In fact, both damaging
      mechanisms are important, their relative contributions depending on cell type,
      cooling rate, and warming rate. A consensus has developed that intracellular
      freezing is dangerous, whereas extracellular ice is harmless. If the water
      permeability of the cell membrane is known it is possible to predict the effect
      of cooling rate on cell survival and the optimum rate will be a tradeoff between
      the risk of intracellular freezing and effects of the concentrated solutes.
      However, extracellular ice is not always innocuous: densely packed cells are more
      likely to be damaged by mechanical stresses within the channels where they are
      sequestered and with complex multicellular systems it is imperative not only to
      secure cell survival but also to avoid damage to the extracellular structure. Ice
      can be avoided by vitrification--the production of a glassy state that is defined
      by the viscosity reaching a sufficiently high value (approximatly 10(13) poises)
      to behave like a solid, but without any crystallization. Toxicity is the major
      problem in the use of vitrification methods. Whether freezing is permitted
      (conventional cryopreservation) or prevented (vitrification), the cryoprotectant
      has to gain access to all parts of the system. However, there are numerous
      barriers to the free diffusion of solutes (membranes), and these can result in
      transient, and sometimes equilibrium, changes in compartment volumes and these
      can be damaging. Hence, the processes of diffusion and osmosis have important
      effects during the introduction of cryoprotectants, the removal of
      cryoprotectants, the freezing process, and during thawing. These phenomena are
      amenable to experiment and analysis, and this has made it possible to develop
      effective methods for the preservation of a very wide range of cells and some
      tissues; these methods have found widespread applications in biology and
      medicine.

PMID- 18080462
TI  - Lyophilization of proteins.
AB  - This chapter describes the methods that can be applied to successfully freeze-dry
      proteins. Laboratory applications are given at small scale, typified by the
      purification of a protein intermediate as part of the analytical characterization
      of a protein, and at intermediate scale, as illustrated by the pilot development
      of a lyophilized protein reference material such as for use in bioassay or
      immunoassay. Advice on common problems with freeze-drying of proteins is also
      given.

PMID- 18080463
TI  - Vacuum-drying and cryopreservation of prokaryotes.
AB  - Traditionally, the ex situ study of prokaryotes (members of Archaea and Bacteria)
      has required access to living cultures. Although it may be possible to maintain a
      small number of strains by serial transfer, such methods are not the best,
      particularly for long-term storage or for keeping a large collection. One of the
      major problems is dealing with the vast range of organisms that have been
      isolated to date. Particularly in the case of methods of cultivating prokaryotes,
      it is almost impossible to give a simple list of media to use. However, general
      principles are outlined that should cover most of the currently known prokaryotes
      in pure culture. The methodologies used for the long-term storage of prokaryotes
      may be divided into those that involve freezing and those that involve vacuum
      drying. The methods described are those that are either used in the Deutsche
      Sammlung von Mikroorganismen und Zellkulturen GmbH (http://www.dsmz.de/index.htm)
      or in other national culture collections.

PMID- 18080464
TI  - Freeze-drying of yeast cultures.
AB  - A method is described that allows yeast species to be stored using a variation on
      the standard freeze-drying method, which employs evaporative cooling in a two
      stage process. Yeast cultures are placed in glass ampoules after having been
      mixed with a lyoprotectant. Primary drying is carried out using a centrifuge head
      connected to a standard freeze-dryer. Once the centrifuge head is running, air is
      removed and evaporated liquid is captured in the freeze-dryer. Centrifugation
      continues for 15 min and primary drying for a further 3 h. The ampoules are
      constricted using a glass blowing torch. They are then placed on the freeze-dryer
      manifold for secondary drying under vacuum overnight, using phosphorus pentoxide
      as a desiccant. The ampoules are sealed and removed from the manifold by melting
      the constricted section. Although the process causes an initial large drop in
      viability, further losses after storage are minimal. Yeast strains have remained
      viable for more than 30 yr when stored using this method and sufficient cells are
      recovered to produce new working stocks. Although survival rates are strain
      specific, nearly all National Collection of Yeast Cultures strains covering most
      yeast genera, have been successfully stored with little or no detectable change
      in strain characteristics.

PMID- 18080465
TI  - Cryopreservation of yeast cultures.
AB  - A method is described that allows a wide range of yeast species to be stored in
      liquid nitrogen while maintaining a high level of viability. Yeast cultures are
      sealed in commercially available polypropylene straws after having been mixed
      with a glycerol-based cryoprotectant. Once placed in a secondary cryotube the
      temperature of the sealed straws is reduced slowly to -30 degrees C in a methanol
      bath over a period of up to 3 h. The straws are then transferred directly to the
      liquid nitrogen and placed in a racking system for long-term storage.

PMID- 18080466
TI  - Freeze-drying fungi using a shelf freeze-drier.
AB  - Lyophilization, the removal of water by freezing and then volatilization at low
      pressure and temperature, has been employed as a standard long-term preservation
      method for many filamentous fungi. The method outlined involves the use of
      standard shelf freeze-drying and skimmed milk as a suspending
      solution/lyoprotectant. This approach has been employed to freeze-dry the
      majority of the 50,000 fungal strains that have been successfully lyophilized at
      the Centraal bureau voor Schimmelcultures (CBS) culture collection
      (http://www.cbs.knaw.nl/).

PMID- 18080467
TI  - Cryopreservation and freeze-drying of fungi employing centrifugal and shelf
      freeze-drying.
AB  - The aim of preserving a fungus is to maintain it in a viable state without change
      to its genetic, physiological, or anatomical characters. There are numerous
      methodologies available to preserve a fungus, but the two methods widely used by
      culture collections (biological or genetic resource centers) to achieve
      successful preservation are cryopreservation with liquid nitrogen using
      controlled-rate freezing and centrifugal freeze-drying. Generic methods are often
      used, but specific variations of a method may be required in order to achieve
      optimal stability. No single method can be applied to all fungi. More recently,
      techniques such as vitrification and encapsulation cryopreservation have been
      used to preserve recalcitrant fungi. The protocols described within this chapter
      have been developed over many years at one of the world's largest culture
      collections of filamentous fungi.

PMID- 18080468
TI  - Cryopreservation of microalgae and cyanobacteria.
AB  - Most culturable cyanobacteria and soil microalgae can be cryopreserved with
      relatively high viability. Furthermore, many freshwater and marine eukaryotic
      algae can also be cryopreserved, but typically with lower post-thaw viability
      levels. However, to date, most dinoflagellates, cryptophytes, synurophytes, and
      raphidophytes cannot be successfully cryopreserved. Marine diatoms can be
      cryopreserved, and often have high viability, although freshwater diatoms have
      thus far proven more problematic. Large numbers of strains have been examined,
      most notably at the four major protistan collections: Culture Collection of Algae
      and Protozoa (CCAP) (UK), The Provasoli-Guillard National Center for Culture of
      Marine Phytoplankton (CCMP) (USA), Sammlung von Algenku Huren Gottingen (SAG)
      (Germany), and The Culture Collection of Algae at the University of Texas at
      Austin (UTEX) (USA), and it has been observed that chlorarachniophytes,
      eustigmatophytes, pelagophytes, phaeothamniophytes, and ulvophytes also have very
      high success rates, comparable with the other green algae and cyanobacteria. It
      has been noted that virtually all algae with a large cell size, as well as most
      filamentous strains, cannot as yet be cryopreserved. There are no known
      fundamental reasons why large and more complex algae cannot be successfully
      cryopreserved. Thus, it is anticipated that further research on the basic
      mechanisms of freezing damage and the empirical development of improved protocols
      will continue to expand the number and diversity of algal taxa that can be
      successfully cryopreserved.

PMID- 18080469
TI  - Cryopreservation of plant cell suspensions.
AB  - The cryopreservation of dedifferentiated cells, grown in suspension culture, is
      one of the portfolio of techniques employed for the long-term conservation of
      higher plant germplasm. Suspension cultures are also important in biotechnology,
      particularly in transformation studies and for the production of specific
      metabolites, and, here, there is also a pressing need for genetically stable,
      long-term storage of cell lines. Cryopreservation of suspension cell cultures can
      be exploited by either slow, or rapid, cooling techniques. During slow cooling
      the extracellular solutions are nucleated and the cells cryodehydrate during
      controlled cooling as a consequence of extracellular ice, to the point where
      their intracellular fluids will vitrify on subsequent transfer to liquid
      nitrogen. In the rapid cooling protocols, the cells are prepared by extreme
      osmotic dehydration, with cryoprotection, before plunging the samples directly
      into liquid nitrogen to achieve vitrification. Extensive success has been
      achieved with both techniques but rapid cooling is, currently, widely favored
      because of its simplicity.

PMID- 18080470
TI  - Cryopreservation of shoot tips and meristems.
AB  - Shoot-tip meristem cryopreservation methodologies are reported for the
      complementary cryoprotective strategies of vitrification and equilibrium freezing
      using traditional controlled-rate freezing and chemical additive cryoprotection.
      Pregrowth, pretreatment, and cold acclimation approaches for the improvement of
      tolerance to liquid nitrogen are also presented. The chapter concludes by
      reporting an analytical protocol that profiles volatile hydrocarbon stress
      markers (for ethylene, hydroxyl radicals, and lipid peroxidation products) during
      cryopreservation. This method uses noninvasive headspace sampling and gas
      chromatography, and it is widely applicable across cryogenic systems.

PMID- 18080471
TI  - Cryopreservation of desiccation-tolerant seeds.
AB  - The cryopreservation of desiccation-tolerant seeds depends on two key steps:
      specimen dehydration in an environment that ensures the attainment of water
      contents below the high-moisture freezing limit; and transfer and maintenance at
      a subzero temperature that may be optimized in relation to the seed-lot moisture
      content and species. Temperatures about 70 degrees C below the glass transition
      temperature (Tg-70) or lower are recommended for seed storage. For fully
      desiccation-tolerant (type I) seeds, cryopreservation success tends to be
      independent of cooling regime and subzero (degrees C) temperature treatment when
      the seeds are dry. However, to maximize recovery of partially desiccation
      tolerant (type II) seeds there can be a requirement for slow cooling, avoidance
      of storage at certain subzero temperatures, and controlled imbibition following
      cryopreservation, particularly for endospermic seeds that are high in lipid.

PMID- 18080472
TI  - Cryopreservation of fish sperm.
AB  - This chapter provides detailed descriptions of the protocol used for fish sperm
      cryopreservation. The principles described can be applied to any species, but
      details are also given for individual fish species. Successful cryopreservation
      of fish spermatozoa depends on a range of factors including the collection of
      high quality sperm, equilibration conditions, choice of cryoprotectant medium,
      cooling/thawing regimes, and conditions for fertilization. Even though some
      general rules can be applied to any fish species, optimization of the protocol is
      needed for each individual species. Furthermore, because sperm derived from
      marine and freshwater fish differs markedly, the described protocol is mainly
      focused on the cryopreservation of sperm for freshwater fish because this poses
      the greater technical challenge.

PMID- 18080473
TI  - Cryopreservation of avian spermatozoa.
AB  - This chapter describes a simple system for cryopreservation of avian spermatozoa
      as pellets, formed by dropping volumes of sperm suspension directly into liquid
      nitrogen with dimethylacetamide as cryoprotectant. The method originates from the
      group at the Research Institute of Farm Animal Breeding and Genetics at St.
      Petersburg-Pushkin and is described here for chicken spermatozoa, but has also
      been adapted successfully for other species, such as Houbara bustards and
      pheasants.

PMID- 18080474
TI  - Cryopreservation of animal and human cell lines.
AB  - The long-term storage of human and animal cell lines is a relatively new branch
      of the science of cryopreservation of living organisms. The need to maintain the
      increasing numbers of cell lines, as they started to emerge from research
      laboratories from the mid-1900s, necessitated a radical approach to the problem.
      The realization that they could survive cryopreservation, and that a slow rate of
      cooling is essential for this survival, led to the eventual discovery of
      cryoprotectants. Subsequent development of mechanical freezers, which can
      accurately control the rate of cooling, now allows cells to be cryopreserved at
      their maximum viability. This chapter outlines the essentials steps for the
      successful preparation, freezing, and storage of cell lines.

PMID- 18080475
TI  - Cryopreservation of hematopoietic stem/progenitor cells for therapeutic use.
AB  - To date, more than 25,000 hematopoietic transplants have been carried out across
      Europe for hematological disorders, the majority being for hematological
      malignancies. At least 70% of these are autologous transplants, the remaining 30%
      being allogeneic, which are sourced from related (70% of the allogeneic) or
      unrelated donors. Peripheral blood mobilized with granulocyte colony stimulating
      factor is the major source of stem cells for transplantation, being used in
      approx 95% of autologous transplants and in approx 65% of allogeneic transplants.
      Other cell sources used for transplantation are bone marrow and umbilical cord
      blood. One crucial advance in the treatment of these disorders has been the
      development of the ability to cryopreserve hematopoietic stem cells for future
      transplantation. For bone marrow and mobilized peripheral blood, the majority of
      cryopreserved harvests come from autologous collections that are stored prior to
      a planned infusion following further treatment of the patient or at the time of a
      subsequent relapse. Other autologous harvests are stored as backup or "rainy day"
      harvests, the former specifically being intended to rescue patients who develop
      graft failure following an allogeneic transplant or who may require this
      transplant at a later date. Allogeneic bone marrow and mobilized peripheral blood
      are less often cryopreserved than autologous harvests. This is in contrast to
      umbilical cord blood that may be banked for directed or sibling (related)
      hematopoietic stem cell transplants, for allogeneic unrelated donations, and for
      autologous donations. Allogeneic unrelated donations are of particular use for
      providing a source of hematopoietic stem cells for ethnic minorities, patients
      with rare human leukocyte antigen types, or where the patient urgently requires a
      transplant and cannot wait for the weeks to months required to prepare a bone
      marrow donor. There are currently more than 200,000 banked umbilical cord blood
      units registered with the Bone Marrow Donors Worldwide registry. In this chapter,
      we describe several protocols that we have used to cryopreserve these different
      sources of hematopoietic stem/progenitor cells, keeping in mind that the
      protocols may vary among transplant processing centers.

PMID- 18080476
TI  - Cryopreservation of human embryonic stem cell lines.
AB  - Two different approaches have been adopted for the cryopreservation of human
      embryonic stem cells (hESCs): vitrification and conventional slow cooling/rapid
      warming. The vitrification method described here is designed for hESCs that grow
      as discrete colonies on a feeder cell monolayer, and are subcultured by manual
      subdivision of the colonies into multicellular clumps. hESCs that are subcultured
      by enzymatic dissociation can more conveniently be cryopreserved by conventional
      slow cooling/rapid warming methods. Although both methods are suitable for use in
      a research context, neither is suitable for cryopreservation of embryonic stem
      cells destined for clinical diagnostic or therapeutic uses without modification.

PMID- 18080477
TI  - Cryopreservation of primary animal cell cultures.
AB  - Cells isolated directly from tissues (primary cultures) have many applications in
      research and applications in the fields of toxicology, pharmacology, and
      virology. Where such preparations remain the only scientific option to achieve
      necessary results it is still possible to refine and reduce the use of animal and
      human sources of the tissue by cryopreservation of the primary cells for later
      use, this reduces the need for fresh tissues and enables improvements in
      standardization through the ability to provide the same cell preparation at
      different times and to different laboratories. The methods described provide
      options for adherent cultures as monolayers, harvested cell suspensions, and also
      lymphocytes isolated from peripheral blood.

PMID- 18080478
TI  - Cryopreservation of red blood cells and platelets.
AB  - Blood cells can be regarded as a classical field of application of low
      temperature biology. Cryopreservation methods have been developed for different
      categories of blood cells namely red blood cells (RBCs) (erythrocytes), platelets
      (thrombocytes), mononuclear cells (i.e., lymphocytes, monocytes), and
      hematopoietic progenitor cells. This chapter outlines the four most commonly
      applied techniques for RBCs and two for platelets.

PMID- 18080479
TI  - Cryopreservation of mammalian semen.
AB  - Mammalian spermatozoa were among the very first cells to be successfully
      cryopreserved and over the last five decades the use of frozen-thawed semen for
      artificial insemination has come to play an important role in domestic livestock
      production. More recently, semen freezing has increasingly been utilized in the
      establishment of genetic resource banks for endangered species. Semen is
      collected, most commonly either by use of an artificial vagina or by
      electroejaculation of an anaesthetized animal, and basic sperm parameters
      assessed. Semen is extended using a TEST-egg yolk-glycerol diluent, packaged in
      0.25-mL plastic straws and slowly cooled to 5 degrees C over a period of 1-2 h.
      Cooled straws are frozen by suspending within liquid nitrogen vapor above the
      liquid nitrogen surface before plunging into the liquid phase. Straws are thawed
      briefly in air before immersing in a 35 degrees C water bath for 15 s, and often
      are used directly for insemination without any further processing.

PMID- 18080480
TI  - Cryopreservation of mammalian oocytes.
AB  - Two methods for the cryopreservation of mammalian oocytes are described. One
      method uses a relatively low concentration of the cryoprotectant propanediol plus
      sucrose and requires controlled-rate cooling equipment to achieve a slow cooling
      rate. Such a method has produced live births from cryopreserved human oocytes.
      The second method described employs a high concentration of the cryoprotectant
      dimethyl sulfoxide plus a low concentration of polyethylene glycol. This method
      involves cooling by plunging standard straws into liquid nitrogen vapor, hence
      avoiding the need for specialized equipment, but requires technical ability to
      manipulate the oocytes quickly in the highly concentrated cryoprotectant
      solutions. Murine oocytes vitrified, using this technique, have resulted in live
      births.

PMID- 18080481
TI  - Cryopreservation of mammalian embryos.
AB  - The cryopreservation of mammalian embryos has expanded over the past 20 yr by
      encompassing a range of sophisticated methods to deal with different
      developmental stages and different sensitivities to low-temperature exposure. We
      have described a method for slow, controlled-rate freezing of early stage embryos
      based on exposure to 1,2-propanediol and sucrose, while the method for late-stage
      (blastocyst) embryos employs mixtures of glycerol and sucrose. Both methods have
      been used for animal and human embryos. A third rapid cooling or "vitrification"
      technique is described, which depends on brief but controlled exposure of
      multicellular embryos to mixtures of glycerol and 1,2-propanediol at high
      concentrations. This technique is used for successful animal embryo
      cryopreservation but is not yet widely applied in the clinic.

PMID- 18080482
TI  - Wrongful termination and workers' compensation: firing an employee with an open
      claim.

PMID- 18080483
TI  - How to integrate CAMBRA into private practice.
AB  - The traditional dentistry approach treated the disease with a limited surgical
      strategy aimed at removing carious lesions on teeth. Today, the dental profession
      is refocusing its efforts to include risk assessment with evidence-based
      diagnosis while also treating the biofilm component of the disease. While there
      is compelling science to support CAMBRA, there are fewer articles with practical
      direction regarding how to integrate CAMBRA diagnostics and treatment into
      clinical practice, which this article addresses.

PMID- 18080484
TI  - The role of dental hygienists, assistants, and office staff in CAMBRA.
AB  - The role of the dental team in caries management by risk assessment is critical
      to successful patient outcomes. Positive patient interactions and communication,
      proper appointment scheduling, diagnostics and data gathering, as well as
      implementation of noninvasive or minimally invasive procedures can be the
      responsibility of all members of the dental team. This article will evaluate the
      role of the clinical and administrative staff in maintaining a practice with a
      focus on disease prevention and management..

PMID- 18080485
TI  - Risky business: influencing people to change.
AB  - The evolution of prevention methods represents a positive development of
      significant value. Managing the behavioral components of prevention is crucial to
      create buy-in by staff and patients. Numerous recommendations for successful
      implementation of CAMBRA are cited. It is important for dentists to establish
      which option works best with each employee, and for the dental care team to do
      the same with each patient in the practice.

PMID- 18080486
TI  - Caries management by risk assessment: implementation guidelines.
AB  - ACT This consensus statement supports implementation of caries management by risk
      assessment in clinical practice by using the following principles: modification
      of the oral flora, patient education, remineralization, and minimal operative
      intervention. The statement includes a list of supporters.

PMID- 18080487
TI  - Heavy pondering on light.

PMID- 18080488
TI  - [Functional identification of the TRPM8 cold receptor in rat prostate epithelial
      cells].
AB  - For the first time by means of electrophysiology we demonstrate functional
      expression of cold/menthol sensitive TRPM8 channel in secretory epithelial cells
      plasma membrane from rat prostate. Under whole-cell patch-clamp technique rapid
      cooling from 33 to 21 degrees C of freshly isolated rat prostate epithelial cells
      elicited the significant outward rectifying membrane current with close to 0 mV
      reversal potential characteristic of TRPM8 activation. Extracellular application
      of chemical analog of cooling, menthol (100 microM) at 33 degrees C evoked
      similar current responses. Cold- and menthol-evoked currents could be detected
      only in elongated epithelial cells, which in prostate slices were labeled with
      anti-cytokeratin 8, suggesting that they belong to the apical secretory
      phenotype. No such current could be detected in round apparently basal epithelial
      cells. We conclude that in normal rat prostate functional expression of TRPM8 is
      restricted to plasma membrane of luminal apical epithelial cells.

PMID- 18080489
TI  - [Synaptic responses and intraganglionic connections of rat superior cervical
      ganglia neurons].
AB  - The rat superior cervical ganglion (SCG) neurones demonstrate responses on the
      threshold stimulation of the cervical sympathetic nerve, extrinsic (ECN) and
      intrinsic (ICN) carotid nerves. Both antidromic and synaptic responses were
      evoked by antidromic stimulation of ECN and ICN. The synaptic responses of each
      neuron differ by great variability amplitudes of the excitatory postsynaptic
      potentials and the currents, the rise time and the time constant decay of the
      postsynaptic current. We hypothesize that this variability of the synaptic
      responces is associated with the spatial distribution of synapses on the
      dendritic tree and on the neuron soma that are innervated by the single axon.

PMID- 18080490
TI  - [The role of nitric oxide and superoxide synthesis in protective mechanism of
      ecdysterone in the heart mitochondria of rats with streptozotocin-induced
      diabetes].
AB  - This study evaluated generation of O2*- and NO in heart mitochondria isolated
      from 9-week old streptozotocin (STZ)-induced diabetic rats and the effect of
      ecdysterone treatment on these parameters. Mitochondria isolated from 9-week old
      placebo-treated rats were used as control. Several parameters were evaluated: O2*
      production, the levels of stable NO metabolites nitrate, nitrite and total
      nitrosothiols, the level of bilirubine (as marker of CO generation), inducible
      (iNOS) and constitutive (nNOS) mtNOS, NADH- dependent nitrate reductase (NR) and
      inducible arginase II (AII) activity. We observed that diabetes was accompanied
      by a significant decrease in nNOS activity, nitrite, total nitrosothiols and
      bilirubine content while iNOS, NR and AII activity, as well as O2*- generation
      was increased in heart mitochondria. Ecdysterone treatment normalized the levels
      of stable NO metabolites, ability to generate superoxide, iNOS and nNOS activity,
      but not bilirubine level, NR and AII activity. These results suggest that
      ecdysterone treatment attenuates diabetes-induced mitochondrial alterations
      protecting against oxidative and nitrosative stresses. Thus, ecdysterone therapy,
      besides its well known importance in the maintenance of glycemic control, may
      help to protect against mitochondrial dysfunction associated to several age
      related disorders.

PMID- 18080491
TI  - [The protective effect of molsidomin in immune ovarian pathology in mice].
AB  - Experimental immune ovarian failure in CBA mice was induced by either
      administration of xenogenic anti-ovarian antibodies (scheme 1) or immunization
      with allogenic ovarian extracts (scheme 2). It was shown that both types of
      treatment impaired the meiotic maturation of oocytes: the number of cells at the
      stages of metaphase I and metaphase II decreased compared to the cells of control
      mice. In both schemes of experiments, impaired oogenesis was accompanied by
      reduction of percentage of viable follicular cells and by increase in the part of
      cells possessing morphological features of apoptosis. In contrast, the number of
      necrotic follicular cells increased in scheme 2 only. The donor of nitric oxide
      molsidomin (10 mg/ kg), when injected an hour before administration of xenogenic
      anti-ovarian antibodies or allogenic ovary extracts, improved the meiotic
      maturation of oocytes and favored follicular, lymph nodes and thymus cells
      survival by decreasing the number of apoptotic and necrotic cells.

PMID- 18080492
TI  - [NADPH-diaphorase neurons and their interrelationship with microvascular vessels
      in the basal forebrain limbic structures and hypothalamus].
AB  - NADPH-diaphorase histochemistry was used to study the distribution and density of
      labeled neurons in the limbic structures and hypothalamus in intact rat. NADPH
      diaphorase positive neurons were registered in the basal forebrain-medial septal
      nucleus (MS), the nuclei of the diagonal band of Broca (VDB, HDB), substancia
      innominata (SI) and the nucleus basalis of Meynert (B). These areas largely
      overlap with the cholinergic CH1-CH4 forebrain system of the rodent brain. The
      order of density of labeled neurons in different regions of the basal forebrain
      was as following sequence: HDB > VDB > SI > B. The highest densities of the
      reactive neurons (> 1000 labeled neurons per section 200x200 microm2) was found
      in the islands of Calleja (ICjs). In the supraoptic (SO) and paraventricular (Pa)
      nuclei of hypothalamus were recorded > 130 and > 100 labeled units, respectively.
      The lowest density of labeled neurons was recorded within the SI-B complex: < 10
      reactive units. Reactive neurons, their dendrites and axon-like processes within
      the ICjs, SO, Pa, the lateral nucleus hypothalamus (LH) often surround arterioles
      which traverse the structures. We suggest that NADPH-diaphorase-reactive (NO
      generating) neurons within the ICjs and hypothalamus are involved in regulation
      of the regional, blood flow (RBF) that is important to adapt the blood flow to
      changes in neuronal activity of the basal forebrain structures.

PMID- 18080493
TI  - [Functional activity of the peritoneal macrophages in mice with concanavalin A
      induced hepatitis].
AB  - Hepatitis of T-cell genesis, a model of autoimmune damage of human liver, was
      caused in mice of CBA line by concanavalin A (Con A). The damage of liver was
      examined by activities of transaminases (alanine aminotransferase, aspartate
      aminotransferase) and alkaline phosphatase in mice blood plasma. Functional
      activity of macrophages in peritoneal fluid was studied by examination of
      phagocytosis of latex particles and oxygen--dependent metabolism (nitro-blue
      tetrazolium- test). We demonstrated that a single intravenous injection of Con A
      in different doses (15 and 30 Mg/kg of body weight) caused acute hepatic damage
      in 20 hours. Weakening of macrophage functional activities may be one of the
      reasons of decrease in dead cells elimination following induction of immune
      hepatitis, it may support inflammatory reaction and promote the development of
      autoimmune process.

PMID- 18080494
TI  - [Effect of benzimidazole and its derivatives on electrical activity of Helix
      albescens Rossm neurons and behavior of rats].
AB  - We studied concentration dependency and the mechanisms of the effect of
      bezimidazole and its new derivatives on electrical processes in Helix albescens
      Rossm. neurons. These compounds appeared to have neurotropic properties dependent
      on their chemical structure and the types of neurons. We determined the
      threshold, optimal and toxic concentration values of the tested substances.
      Benzimidazole and 2-trifluoromethylbenzimidazole at concentrations of 10(-3) and
      10(-2) M elicit both excitatory and inhibitory postsynaptic potentials on soma
      membrane of some pacemaker and non-pacemaker neurons and even cause a strong
      depolarization. The membrane of pacemaker neurons (namely, neuron RPa2) was found
      to have at least two spatially separated trigger sites with different trigger
      mechanism of action potential. After single intraperitoneal injection (50 mg/kg)
      of the substance solution, the tested compounds based on the discovered effects
      were separated into two groups. The first group inhibits locomotion and
      psychoemotional state of rats, the second group elicits the opposite effect. We
      found that at 100 and 150 mg/kg all tested substances inhibit the animal's
      activity.

PMID- 18080495
TI  - [Effect of paxilline on Ca(2+)-dependent K+ current in smooth muscle cells
      isolated from rat vas deferens].
AB  - The properties of the outward Ca(2+)-dependent K+ current (KCa) were investigated
      in single smooth muscle cells (SMCs) isolated from epididymal part of the rat vas
      deferens (RVD) using amphotericin B perforated patch-clamp technique. The complex
      kinetic of the net outward current elicited by positive voltage steps from -80 mV
      to +40 mV suggested the presence of several components of this current. KCa
      current was separated from the net outward current by removal of Ca2+ from the
      external solution. KCa was characterized by slow kinetics of current activation
      and decay. Mycotoxin paxilline, the selective blocker of the large conductance
      KCa channels, inhibited KCa current in a dose-dependent manner. At the
      concentration of 70 nM paxilline evoked 50% inhibition of KCa and at 1 mkM
      complete suppression of KCa current was achieved. The blocking effect of low
      concentrations of a nonselective KCa channels inhibitor tetraethylammonium (TEA)
      was compared to that of paxilline. The external application of 0.3 mM TEA
      inhibited KCa current similarly to 1 mkM of paxilline. Finally, we studied the
      effect of paxilline on the resting membrane potential ofRVD SMCs. Paxilline (1
      mkM) did not affect the membrane potential of SMCs with the resting potential in
      the range of -60 to -40 mV. However, at potentials more positive than -40 mV
      application of paxilline significantly (up to 15 mV) depolarized the membrane of
      SMCs. These results suggest that the large conductance KCa channels in RVD SMCs
      do not contribute to the resting membrane potential but could serve as a
      hyperpolarizing mechanism at the significant membrane depolarizations.

PMID- 18080496
TI  - [Age-dependent state of the skin blood vessels].
AB  - Skin microcirculation was studies in 120 healthy people of different age and in
      individuals with signs of senile slackness. It was shown that ageing is
      accompanied by impairment of microcirculation which is determined by
      morphological alterations in microvessels, alterations in microhemodynamics and
      changes in rheological properties of blood. Senile slackness of the skin is
      characterized by the reduced quantity of functioning capillary loops which
      resembles the microcirculatory structure of aged people.

PMID- 18080497
TI  - The state of thyroid gland and psychical development of socially deprived
      children during treatment by "Iodide-100".
AB  - Socially deprived children of school age, who live on the territory of moderate
      iodine deficiency and under conditions of preventive treatment with "Iodide-100"
      drug have been examined. The following parameters have been examined: the size of
      thyroid gland, its functional activity and the level of children's mental
      development. The correlation link between the sizes of thyroid gland and the
      level of mental development, psychic functions of examined children has been
      established. Preventive treatment with "Iodide-100" significantly improved the
      investigated parameters.

PMID- 18080498
TI  - [Effect of thyroidectomy on energetics of isometric muscle contraction in white
      rats].
AB  - The effect of thyroidactomia on parameters of energetics of isometric
      contractions of front shin--bone muscle of white rats is studied in in situ
      experiments. It is shown that experimental atiriosis lengthen considerably the
      latent period of muscle contractions (+95%) considerably reduce (in 5.5 times)
      the speed of it contraction in first phase of contraction act and also
      considerably increase the time (+37%), which necessery for developing maximum
      strength of contraction. Thyroidactomia with general negative influence on
      ergothropic characteristics of isometric muscle contraction decrease considerably
      the expenditure of thermal energy on maximum strength of contraction unit (-17%)
      or on middle isometric tension unit (-9.3%).

PMID- 18080499
TI  - [Periodic motor-secretory activity of the stomach in disbalance of its regulatory
      mechanisms].
AB  - The periodic gastric motor-and-secretor activity in modeling of disbalance of
      autonomic nervous regulation in chronic fistula canine experiments was studied.
      It was found that autonomic nervous disbalance at the first stages was
      accompanied with reorganization of periodic gastric motor and secretor phase
      lengths which resulted in shortening of gastric basic myoelectrical rhythm period
      (BMRP), appearing of gastric acid secretion in fasted state and increasing of
      secretor response to exogenous histamine stimulation. Indeed, the gastric motor
      rhythms appeared to be more sensitive to changes in activity of regulatory
      mechanisms than the functional activity of the gastric secretor glands. Long-term
      disbalance of regulatory mechanisms caused the "regulatory rejection", which was
      associated with increasing of duodenogastric reflux and increasing of gastric
      BMRP, as well as with decreasing of gastric mucosal defending properties. We
      hypothesize that nonadrenergic noncholinergic pathway may play a role in
      reorganization of the observed gastric motor-and-secretor activity.

PMID- 18080500
TI  - [Psychophysiological characteristics of task solving of complexity-related
      tasks].
AB  - The impact of tasks complexity and factors of professional qualities of different
      groups of tested individuals with different occupational orientation on the
      outcome of task performance have been analyzed. The precise regularities of
      intellectual and temporal components of task complexity's components on activity
      quality have been revealed. The regularities found are proposed to use for
      assessment of professional suitability level.

PMID- 18080501
TI  - [Endocrine and immune interactions in healthy individuals during measured
      physical exercise].
AB  - The purpose of the study was to determine the effect of exercise on
      neuroendocrine and immune systems in healthy individuals. The small amount of
      correlation links between examined indexes points to a balanced state of
      neuroendocrinal and immune systems in healthy persons. The increase in the amount
      of correlation links under exercise of miscellaneous intensity in healthy
      individuals points to a functional tension of the examined systems. The analysis
      of variance revealed the dose-dependent effect of exercise on indexes of
      neuroendocrine and immune systems, and also the exercise-mediated effect of
      hypophysial-adrenal system indexes on cell immunity in healthy persons.

PMID- 18080502
TI  - [Frequency and prognostic value of chromosome abnormalities in multiple myeloma].
AB  - Chromosomal aberrations have been shown to significantly affect survival in
      multiple myeloma (MM), but few cytogenetic analyses among Japanese MM patients
      have been reported. Using a commercial laboratory, we performed interphase
      fluorescent in situ hybridization (FISH), as well as a conventional metaphase
      cytogenetic study (G-banding), among 106 of 131 patients between April 1997 and
      February 2007. Karyotype abnormalities were found in 21.2% (21 of 99 patients).
      Del(13q), del(17p), del(11q), t(11;14) and t(4;14) were detected by FISH in 36.0%
      (31/86), 24.7% (19/77), 7.6% (5/64), 18.2% (12/66) and 10.4% (7/67) of patients,
      respectively. The prevalence of abnormalities detected by G-banding was lower
      than that reported in European countries, but when compared with FISH studies, no
      difference was observed. Prognostic analyses of patients with these abnormal
      chromosomes revealed that those with abnormal karyotype and del(13q), t(4;14), as
      detected by FISH, had significantly poorer survival. This study suggests that the
      prevalence of chromosome abnormalities among Japanese patients is similar to that
      for European populations, and that chromosome studies by G-banding and FISH are
      essential to predict survival.

PMID- 18080503
TI  - [The unification of hematopoietic stem cell transplantation registry in Japan and
      establishment of the TRUMP system].
AB  - There are four registries of hematopoietic cell transplant in Japan; the Japan
      Society for Hematopoietic Cell Transplantation (JSHCT), Japanese Society of
      Pediatric Hematology, Japan Marrow Donor Program and Japan Cord Blood Bank
      Network, each playing an important role in society by reporting the number and
      outcomes of transplantations and contributing new findings obtained from studies
      on individual topics. However, there have been a number of difficulties with
      analyzing data in overlapping registries and multiple databases at centers
      affiliated with each of the four registry organizations. JSHCT was pivotal in
      orchestrating the computerization and unification of hematopoietic stem cell
      transplant registries for the purpose of resolving these issues and providing a
      more accurate awareness of hematopoietic stem cell transplantations performed in
      Japan. JSHCT played a central role in developing the "Transplant Registry Unified
      Management Program (TRUMP)" to enable transplant institutes to manage patient
      information with emphasis on convenience to institutes, safety of patient
      information, and quality of data management. While enhancing domestic registries,
      the program seeks to coordinate with other hematopoietic cell transplant
      registries around the world to contribute to the development of registries
      throughout Asia.

PMID- 18080505
TI  - [Long-term survival after autologous peripheral blood stem cell transplantation
      in a patient with primary AL amyloidosis complicating congestive heart failure].
AB  - A 44-year-old man was admitted to hospital because of respiratory distress and
      progressive edema in the lower extremities. He was diagnosed as having congestive
      heart failure, but his condition improved following intensive care.
      Echocardiogram revealed a thickened interventricular septum, insufficient
      diastolic function, and granular sparkling pattern in the ventricular wall.
      Pathological examination of a myocardial biopsy specimen showed the deposition of
      AL amyloid, resulting in a diagnosis of AL amyloidosis. He was then referred to
      our hospital for treatment. After a course of high-dose dexamethasone therapy,
      peripheral blood stem cells induced by the administration of granulocyte colony
      stimulating factor were harvested. He then received high-dose melphalan (HDM)
      with autologous peripheral blood stem cell transplantation (auto-PBSCT) support,
      leading to complete remission. He has been well for more than three years after
      the transplantation and enjoys the same daily life as before the onset of
      symptoms. HDM/auto-PBSCT for AL amyloidosis confers a higher response rate and
      longer survival than conventional chemotherapies; however, treatment-related
      toxicity is also high. Refinements of treatment strategies are urgently needed.
      This case provides insights into appropriate strategies for HDM/auto-PBSCT for AL
      amyloidosis with regard to patient selection, the best induction therapy, and the
      risk-adjusted melphalan conditioning dose; all of which should be confirmed by
      randomized controlled trials.

PMID- 18080504
TI  - [Encouraging results of stem cell transplantation following a melphalan-preceding
      intensified preparative regimen for refractory acute leukemia in children].
AB  - The results of allogeneic stem cell transplantation for patients with
      chemotherapy-resistant non-remission acute leukemia have been very poor. We have
      used a melphalan-preceding intensified preparative regimen in which a six-day
      interval is set between melphalan 70 mg/m2 and the main part of the preparative
      regimen to avoid toxicity in 15 consecutive pediatric patients with refractory
      acute leukemia. Only one patient died of transplant-related toxicity within 100
      days of transplant. One patient had refractory anemia originating from donor
      cells at three months after transplant. Eight patients relapsed at a median of
      six months after transplant; therefore, five of 15 patients have been in complete
      remission (CR) for a median of 61 months. Four of six patients who did not have
      blasts in their peripheral blood before melphalan are in CR This method seems to
      be safe and effective for refractory acute leukemia.

PMID- 18080506
TI  - [Amylase-producing multiple myeloma: a case report].
AB  - A 80-year-old man was admitted because of acute-onset thrombocytopenia and renal
      failure. He was diagnosed with Bence Jones (lambda) -type multiple myeloma
      associated with sepsis with methicillin-resistant Staphylococcus aureus. On
      admission, serum amylase activity was elevated to 1,814 IU/l (98% salivary type;
      S-amylase). Several days after admission, he developed bilateral myelomatous
      pleuritis. The activity of S-amylase in the effusion was 5,495 IU/l. Myeloma
      cells in the pleural effusion were positive for cytoplasmic amylase with an
      antibody against human amylase. High S-amylase activity was detected in the
      supernatant of cultured myeloma cells in the effusion. Furthermore, S-amylase
      gene expression was detected by RT-PCR. A diagnosis of amylase-producing multiple
      myeloma was made. The patient died of renal insufficiency complicated by severe
      DIC. We report a rare case of amylase-producing myeloma confirmed by
      immunocytochemistry, culture method, and gene expression.

PMID- 18080507
TI  - [Splenic marginal zone lymphoma associated with autoimmune hemolytic anemia
      treated with splenectomy and rituximab].
AB  - A 51-year-old woman, who presented with dyspnea on effort and was diagnosed with
      autoimmune hemolytic anemia in July 2004, was suspected of having splenic
      marginal zone lymphoma (SMZL) because of clonality of B cell on bone marrow and
      splenomegaly. She underwent splenectomy, and histopathological examination of the
      resected specimen confirmed the diagnosis of SMZL. The patient was treated with
      rituximab, and complete remission was achieved. Up to the present, three years
      after diagnosis, the patient has shown no evidence of progression.

PMID- 18080508
TI  - [Elevation of Epstein-Barr virus (EBV)-DNA in the peripheral blood of a patient
      with age-related EBV-associated B-cell lymphoproliferative disorder].
AB  - A 69-year-old man was admitted to our hospital with fever and right neck
      lymphadenopathy. A neck lymph node biopsy was performed. In the specimens,
      immunoblasts were present with an admixture of small T lymphocytes and
      macrophagocytes. Immunohistochemcal staining of immunoblasts was positive for
      CD20, CD30 and EBER. Epstein-Barr virus (EBV) serology showed elevated IgG
      antibody to VCA, and EBV DNA was detected in the peripheral blood. Since he
      showed latency II without immunodeficiency disease, we diagnosed age-related EBV
      associated B-cell lymphoproliferative disorder (EBV-LPD) as a result of aging and
      EBV infection. He was treated with 6 courses of the CHOP regimen plus rituximab,
      and achieved complete remission. EBV-DNA became undetectable at remission. In age
      related EBV-LPD, there is some possibility that EBV-DNA in the peripheral blood
      is valuable as a tumor biomarker.

PMID- 18080509
TI  - [Severe systemic edema correlated with serum VEGF titer in a patient with
      angioimmunoblastic T-cell lymphoma].
AB  - A 73-year-old woman was admitted with generalized lymphadenopathy, marked
      protrusion of the abdomen, severe systemic edema, oliguria, and dyspnea.
      Histological examination of a cervical lymph node specimen showed a typical
      structure of angioimmunoblastic T-cell lymphoma. CT scan revealed whole
      paraaortic lymphadenopathy, marked edematous lesions in the subcutaneous tissues
      and mesenterium, but small amounts of pleural effusion and ascites. This patient
      achieved complete remission after 5 courses of chemotherapy, a first course of
      CHOP followed by 4 courses of hyper CVAD plus high-dose MTX/AraC regimen
      alternatively. Her body weight was 58 kg on the day of admission and decreased to
      41kg after 5 courses of chemotherapy, accompanied with symptomatic improvement.
      We checked the kinetics of serum Vascular endothelial growth factor (VEGF)
      concentrations during the 5 courses of chemotherapy. Pretreatment serum level of
      VEGF was high and declined gradually within the normal range. The serum VEGF
      value was positively correlated with body weight (r = 0.95). Immunohistochemical
      study of the biopsy specimen revealed that endothelia of the venules and some
      dendritic cells were positive for VEGF. We speculated that significant edematous
      changes in this patient were associated with VEGF, which is known as a vascular
      permeability factor based on its ability to induce vascular leakage.

PMID- 18080510
TI  - [Multiple myeloma accompanying splenic amyloidosis and overwhelming
      pneumococcemia].
AB  - We present the case of an 84-year-old woman with multiple myeloma who developed
      overwhelming pneumococcemia. Significant pathologic findings of amyloidosis were
      confirmed in the spleen, adrenal glands, kidneys, liver and bone marrow on
      autopsy. In particular, the spleen was almost replaced by diffuse linear
      deposition of amyloid, and residual lymphoid tissue was scant. There is a well
      established association between asplenia and a predisposition to fulmination,
      frequently with fatal bacterial infection. In this case, functional hyposplenism
      as a result of amyloid replacement of the spleen led to overwhelming
      pneumococcemia. Functional hyposplenism due to amyloidosis predisposes patients
      to septicemia. As bacterial infections are a common complication in patients with
      multiple myeloma, it is important to know whether they have accompanying splenic
      amyloidosis. If there are findings of hyposplenism, it may be necessary to
      establish strategies to prevent fatal infection. Thought needs to be given to
      providing detailed education, and prophylactic or stand-by antibiotics for such
      patients.

PMID- 18080511
TI  - [Topical steroid injection for refractory oral chronic graft-versus-host
      disease].
AB  - The standard treatment for refractory oral chronic graft versus host disease
      (GVHD) has not been established. We present a case of AML accompanied by oral
      chronic GVHD in a 55-year-old man after allogeneic stem cell transplantation. The
      stomatitis of the patient was prolonged for a year and resistant to standard
      immunosuppressant therapy, including systemic administration of prednisolone and
      tacrolimus; however, local injection of 0.2% dexamethasone (0.5 mg per cm2) into
      the ulcerative area was drastically effective in improving refractory mucositis
      and mitigated a vicious cycle of mucosal damage and poor oral hygiene.

PMID- 18080512
TI  - [Varicella-zoster virus meningoencephalitis without skin manifestation in an
      allogeneic bone marrow transplantation patient successfully treated with
      aciclovir].
AB  - This report describes a 56-year-old man who developed meningoencephalitis as a
      result of varicella-zoster virus (VZV) without dermatomal manifestations. The
      patient received an allogeneic bone marrow transplantation for malignant
      lymphoma, and during treatment for chronic graft-versus-host disease, he
      presented with a fever and headache. Cerebrospinal fluid analysis revealed an
      increased cell count with lymphocyte predominance and an extremely high amount of
      VZV DNA, and an MRI study showed multiple lesions of increased T2 intensity
      within deep white matter regions. Meningoencephalitis was diagnosed and the
      patient was successfully treated with aciclovir administered at a dose of 30
      mg/kg/day for four weeks.

PMID- 18080513
TI  - [The present situation of the National University Hospital four years after its
      set-up as corporation].

PMID- 18080514
TI  - [Self-assesed quality of life in patients who underwent surgery for asymptomatic
      meningiomas].
AB  - The aim of our study was to assess the quality of life (QOL) of patients operated
      on for asymptomatic meningioma and to assess the correlation between QOL and
      operative complications. Of 21 surgically treated patients, 6 (28.6%) presented
      with persistent neurological impairments or events considered to be treatment
      related. Seventeen patients participated in the QOL survey using MOS Short-Form
      36-Item Health Survey (SF-36) for health-related QOL issues and the Hospital
      Anxiety and Depression Scale (HADS) for anxiety nd depression assessment. The
      mean scores for each of the 8 domains of SF-36 were comparable with these of a
      Japanese reference population. When we divided the patients into 2 groups
      according to the degree of headache, activity of daily living, or complications,
      the QOL of patients with persistent headache declined in the SF-36 domains
      related to physical function and vitality. Minor neurological impairments
      developed by 4 patients did not affect their QOL. In conclusion, surgery for
      asymptomatic meningioma has no negative impact on postoperative QOL if the
      surgical complications are minor. On the other hand, physical activities in some
      patients were hampered due to persistent headache. Besides the treatment-related
      morbidity and mortality rates, QOL issues should also be included in treatment
      indications for asymptomatic meningioma.

PMID- 18080515
TI  - [Transarterial NBCA embolization with transvenous partial outflow obstruction for
      superior petrosal sinus dural arteriovenous fistula: a case report].
AB  - We encountered a case of superior petrosal sinus dural arteriovenous fistula (SPS
      DAVF) which was treated by a combination of a transvenous and a transarterial
      approach after the failure of the transvenous approach alone. A 69-year-old man
      presented with a complaint of progressive left bulbar conjunctival conjestion,
      exophthalmos, and impaired vision. Cerebral angiography revealed a left SPS DAVF
      fed by the left middle meningeal artery, the meningeal branches of the left
      internal carotid artery and the left posterior meningeal artery. Venous drainage
      proceeded through the cavernous sinus (CS) toward the left superior ophthalmic
      vein (SOV). Transvenous embolization via the SOV was indicated because the left
      ipsilateral inferior petrosal sinus contributed to the normal venous return.
      However the microcatheter to the CS couldn't go through the tortuous SOV. Next a
      transarterial NBCA (n-butyl-cyanoacrylate) embolization of the affected sinuses
      was performed under arterial flow control with balloons and the partial coil
      embolization of the origin of the SOV. The coils in the SOV trapped NBCA and the
      sinuses were filled slowly with NBCA. The postoperative angiogram confirmed
      complete obliteration of the DAVF and the patient's ocular symptoms disappeared.
      DAVF is usually difficult to treat by transarterial embolization with NBCA
      because of its multiple feeders and high flow drainage. We should therefore
      carefully observe its structure and the blood flow change with 3D-DSA and the
      selective angiography while embolizing the DAVE.

PMID- 18080516
TI  - [Foraminal stenosis of the lumbar spine treated by decompression with an
      ultrasonic bone curette: a case report].
AB  - Lumbar foramimal stenosis is one of the important disorders underlying radicular
      symptoms and unrecognized or recurrent foraminal stenosis may result in failed
      back surgery. We report a 47-year old man with foraminal stenosis of the lumbar
      spine associated with a bone spur at the pars interarticularis. He suddenly
      experienced severe right leg pain, lumbago and gait disturbance. Radiographic
      studies revealed foraminal stenosis on the right L5/S1associated with a bone spur
      at the pars interarticularis. There was no dural sac compression by
      spondylolysis. As his symptoms failed to respond to conservative treatment, he
      underwent decompression without fusion with an ultrasonic bone curette. We
      performed lateral fenestration and foraminotomy at the right L5/S1 using the
      extraforaminal approach. After partial foraminotomy, the right L5 nerve root was
      compressed by the bone spur at the pars interarticularis. For satisfactory
      decompression we removed the bone spur using an ultrasonic bone curette. His
      symptoms disappeared immediately after surgery. Although long-term follow-up is
      necessary, we suggest that microdecompression with an ultrasonic bone curette is
      a useful method to treat patients with foraminal stenosis of the pars
      interarticularis.

PMID- 18080517
TI  - [A case of ruptured internal carotid artery aneurysm mimicking pituitary
      apoplexy].
AB  - A 48-year-old female presented with a sudden onset of headache and visual
      impairment. Nineteen years before, she had undergone a transsphenoidal surgery
      for a prolactin producing pituitary adenoma at our hospital without
      intraoperative arterial bleeding. On arrival, she exhibited dilated pupils and
      loss of bilateral visual acuity, but improved immediately after all examinations.
      MRI revealed a pituitary tumor with intratumoral hemorrhage, intraventricular
      hemorrhage and subdural hemorrhage. Cerebral angiography revealed a left
      intracavernous carotid artery aneurysm. Her medical history and radiological
      findings suggested the rupture of a de novo aneurysm causing a hemorrhage into a
      pituitary adenoma mimicking pituitary apoplexy. Endovascular occlusion of the
      aneurysm was performed by use of platinum coils. Because of rapid improvement of
      visual acuity, administration of terguride was chosen for shrinking the pituitary
      adenoma. If a pituitary adenoma is present, the possibility of a coincidental
      aneurysm should always be considered. This association should be kept in mind
      when evaluating any case of pituitary apoplexy.

PMID- 18080519
TI  - [Operative neurosurgery: personal view and historical backgrounds (4). Selective
      amygdalohippocampectomy SAHE].
AB  - Selective amygdalohippocampectomy SAHE has been pioneered by Yasargil et al in
      the mid 1970 within the scope of surgical treatment for intractable mesial
      temporal lobe epilepsy MTLE. In this article, the author has emphasized
      microsurgical points to be kept in mind in carrying out the procedure from the
      experience of just more than 200 surgeries performed by himself during the last
      14 years. Historical backgrounds of development of this technique, necessary
      topographic anatomy, perioperative management and our results were also
      presented. (1) Simple temporal lobectomy (S-lobectomy)--> Epilepsy temporal
      lobectomy (E-lobectomy)--> SAHE has been the way of development, in which the
      amygdala and hippocampus are resected together at Elobectomy while not at S
      lobectomy. At SAHE, the whole temporal lobe remains intact in order to preserve
      cognitive function as much as possible, although part of the temporal stem is cut
      as transsylvian access rout to the temporal horn and the hippocamopus. For a
      novice of this surgery, it is recommended to begin with S-lobectomy then proceed
      to SAHE after having trained himself by cadaver dissection. (2) Among several
      approaches for hippocampectomy, the transsylvian SAHE is considered to remain as
      a standard access to the amygdala and hippocampus also on the dominant
      hemisphere. Furthermore this approach can be used for other fields of
      neurosurgery: tentorial edge meningiomas, P2-P3 junction aneurysms and lesions of
      the insula and basal ganglia. (3) As for the method of SAHE, after having entered
      through the temporal stem into the temporal horn, the hippocampus is dissected
      between the medial margin of the collateral eminence and the tela chorioidea 
      fimbria hippocampi. By this way, most of the amygdala and anterior 2/3 of the
      hippocampus can be extirpated. En bloc resection enables precise histological
      examination and further molecular biological research considered to be
      indispensable for understanding the pathophysiology and treatment of intractable
      MTLE. (4) Following structures should be preserved at the time of SAHE.
      Laterocaudal group in the vicinity of the tentorial margin: Oculomotor nerve,
      posterior cerebral artery PCA with posterior communicating artery Pcom, medial
      posterior choroidal artery, A. temporalis posterior, trochlear nerve.
      Mediocranial group in the vicinity of the brain stem: Crus cerebri, AchoA,
      Tractus opticus, A. parietooccipitalis, Corpus geniculatum laterale. (5) In order
      to avoid surgical complications to be kept in mind. 1: AchoA should be preserved
      at any cost. 2: hemorrhagic diathesis due to longstanding medication of
      antiepileptics especially valproate should be corrected with fresh frozen plasma
      FFP, thrombocyte-preparation and/or Minirin. (6) Good results (Engel I+II) to
      stop or alleviate intractable seizures remarkably could be obtained in more than
      80% of patients in our previous report and also in this series of consecutive 190
      cases. Strict indication based on presurgical epileptological examinations
      including special electroencephalography EEG leading like Foramen ovale
      electrode, selective Wada test and interdisciplinary discussion are mandatory.
      These careful procedures bring good outcome by preventing complications
      especially postoperative deterioration of cognitive function.

PMID- 18080518
TI  - [Three cases of internal carotid artery dissection due to trivial trauma].
AB  - Three cases of internal carotid artery (ICA) dissection due to trivial trauma
      were reported. A 14-year-old, previously healthy, girl developed left hemiparesis
      after jogging. MRI sh owed cerebral infarction in the right basal ganglia and the
      MR angiography (MRA) revealed luminal narrowing of the right ICA as well as
      pseudolumen at the origin of the right ICA. She was treated with antithrombotic
      therapy. Follow-up MRA demonstrated normal signal in the right ICA. A 23-year-old
      woman admitted to the hospital because of minor facial injury due to a traffic
      accident. Although she had no apparent symptom, follow-up CT, one day after
      presentation,. showed cerebral infarction in the right basal ganglia. Angiography
      showed diminished luminal diameter of the right ICA. She was treated with
      antithrombotic therapy and follow-up angiography showed reconstitution of normal
      lumina of the right ICA. A 34-year-old woman was referred to our hospital because
      of transient ischemic attack following swimming. Neurological examination was
      normal and MRI did not show any ischemic lesion. MRA revealed diminished signal
      in the left ICA as well as string and pearl sign at the origin of the left ICA.
      She was treated with antithrombotic therapy, and follow-up angiography showed
      normalization of the left ICA. Cervical ICA dissection due to trivial trauma
      usually appears as an eccentric tapered stenosis arising at the origin of the ICA
      and resolves with complete or excellent recovery in most cases. Surgical or
      endovascular treatment should be reserved for patients who have persistent
      symptoms of ischemia despite adequate antithrombotic treatment.

PMID- 18080520
TI  - [Magnetic resonance imaging and pathology in epilepsy (5). Cavernous angioma and
      arteriovenous malformation].

PMID- 18080521
TI  - [Progress in understanding moleculr mechanisms of oncogenesis, and novel methods
      of tumor growth control].
AB  - Malignant tumor develop from cells with distorted signaling pathways controlling
      proliferation, migration, viability, differentiation, and genome integrity, as
      well as their influence on microenvironment. Progress in understanding molecular
      mechanisms of such alterations has led to the elaboration of new methods of anti
      tumor therapy based on the modulation of the activity of molecules playing a key
      role in tumor development (so-called "target therapy"). The paper describes basic
      mechanisms of the development of cell features determining malignant phenotype
      and new possibilities for its correction. In particular, recent finding
      concerning the role of reactive oxygen species in oncogenesis and anti-tumor
      therapy are considered.

PMID- 18080522
TI  - [Adoptive immunotherapy of malignancies].
AB  - The results of the studies show that mononuclear leukocytes isolated from human
      peripheral blood, malignant effusions, and surgically removed spleen can be
      generated into lymphokine-activated killers (LAK) characterized by high anti
      tumor activity. LAKs may be used foradoptive immunotherapy of malignant effusions
      and the prevention of tumor recurrence in oncological patients after radical
      surgery.

PMID- 18080523
TI  - [New approaches to search for antitumoral compounds].
AB  - The authors discuss the present-day state of search for antitumoral compounds at
      Blokhin Russian Oncological Research Center and promising approaches including
      computer technologies as means of search for new anticancerous targets and drugs.

PMID- 18080524
TI  - [Genetic and epigenetic factors of cervical tumor progression].
AB  - Infection with high risk papilloma viruses (HPV types 16, 18, and relative ones)
      initiates the development and progression of uterine neck cancer. The viral
      genome is found in pre-tumorous lesions (stage I to III intraepithelial
      neoplasias--CIN) and carcinomas, persisting in cells in episomal or integrated
      state. In all tumors, there is the expression of two viral transforming genes, E6
      and E7, the main function of which is the inactivation of genes that suppress
      tumoral growth, p53 and retinoblastoma gene. In CIN and carcinomas, losses of
      heterozygosity are found in various chromosomes, mainly in the areas of
      suppressor genes; some of them can be specific for certain stages of the
      malignant process. Among epigenetic alterations, the main significance for the
      progress of the disease belongs to the methylation of the promoter areas of the
      genes involved in the process of cell division, which may be specific for each
      separate tumor and appears in approximately 30 to 40% of tumors. Another
      important epigenetic alteration is the increase in the expression of p16ink4a
      gene, which is the inhibitor of cyclin-dependent kinases; this appears at CIN I
      stage and may serve as an additional early diagnostic marker. Telomerase activity
      has been identified in all uterine neck tumors, but each tumor has its own
      spectrum of spliced RNA coding this enzyme. Expression microchip technique has
      shown that each tumor is individual according to the spectrum of "working" genes,
      and this spectrum varies in the process of tumor progression.

PMID- 18080525
TI  - [The clinical significance of immunohistochemically detectable Ki-67 protein in
      renal cell carcinoma].
AB  - Great attention is paid to renal cell carcinoma (RCC) due to the growth of its
      prevalence. This paper is dedicated to the matching of classic clinical and
      pathological prognostic factors to the character of the expression of
      proliferation marker Ki-67 in this kind of cancer. The proliferative activity was
      analyzed in 101 RCC cases by immunohistochemical assays using antibodies to Ki
      67. In aggressive RCC and Fuhrman grade 3 to 4 tumors, Ki-67 level was found to
      be high more often. Besides, time to the appearance of remote metastases was
      significantly shorter, and total survival rate was significantly lower in RCC
      with high proliferative activity vs. low.

PMID- 18080526
TI  - [Mechanisms of the invasion of normal and malignant cells].
AB  - Different examples of invasion in normal ontogenesis and during the growth of
      malignant genetically altered cells are discussed. The invasive migration of
      single epithelial cells or cell groups may be regarded as pathological variants
      depending on complete or partial epithelio-mesenchymal transformation. A very
      special new type of epithelial cell dissemination from the monolayer was observed
      in our experiments with epithelial cells hyperexpressing transfected RhoA gene.
      In these experiments, mitotic cells were squeezed out of the contracted monolayer
      into a fluid medium, floated passively in this medium, and settled at the
      substrate forming new islands. It is important to find whether this type of
      dissemination not associated with active cell movements can take place in tumors
      in vivo.

PMID- 18080527
TI  - [The incidence of malignant tumors and mortality caused by them in Commonwealth
      of Independent States in 2005].
AB  - The world's incidence of cancer is 10.9 million new cases each year. In developed
      countries cancer in the second cause of death after cardiovascular diseases. In
      Russia, the number of patients with a newly established diagnosis of a malignant
      tumor increased by 4.6% in 2000-2005 reaching 469.2 thousands. Standardized
      indices of cancer incidence in Commonwealth of Independent States (CIS) were the
      highest in Belarus (312.5 per tens of thousand in men and 217.6 per tens of
      thousand in women), Russia (270.8 per tens of thousand and 196.8 per tens of
      thousand), and Kazakhstan (234.0 per tens of thousand and 171.4 per tens of
      thousand), lower in Armenia (201.3 per tens of thousand and 143.2 per tens of
      thousand) and Moldova (185 per tens of thousand and 162.2 per tens of thousand),
      and minimal in Azerbaydzhan (85.6 per tens of thousand and 73.5 per tens of
      thousand) and Kyrgyzstan (104.8 per tens of thousand and 115.3 per tens of
      thousand). The number of deaths caused by cancer is 6.7 million per year. In CIS,
      cancer-related mortality fell in Belarus (by 6.7% and 4.7% among men and women,
      respectively) and Kazakhstan (by 9.3% and 7.7%), while in Armenia it grew
      significantly (by 37.5% and 24.7%). In Russia, cancer-related mortality in 2000
      2005 decreased by 2.6% in men and 0.8% in women. In Russia, Kazakhstan, and
      Armenia, the incidence of cancer of prostate grew more intensively than that of
      other localizations. Mortality caused by colon cancer grew in Russia and Armenia
      (both genders) and Belarus (women); skin cancer mortality grew in Belarus and
      Kazakhstan (men); breast cancer mortality grew in Armenia.

PMID- 18080528
TI  - [The role of andrology as a field of reproductive medicine in the solution of
      demographic problems in Russia].
AB  - Under the conditions of a deepest demographic crisis, which is progressing in
      Russia and has led to the fact that Russian population diminishes by 1 million
      each year, the development of andrology should be considered a very important
      link in the state system of measures taken to increase birth rate. Andrology is
      an essential field of reproductive medicine and should receive a status of an
      individual medical specialty. At the same time, andrology should be organically
      connected with obstetrics and gynecology, which would provide effective
      diagnostics and treatment of the infertile marriage. It would be baneful and
      inappropriate to refer to andrology as one of officially recognized medical
      specialties such as urology, endocrinology, dermatovenerology, surgery, sexology
      etc. Andrology is a new polydisciplinary and multisectoral medical field
      requiring multifaceted biological and medical knowledge and special training of
      doctors; it does not tolerate narrowly specialized professional thinking and
      acting from a doctor working in this complicated medical field.

PMID- 18080529
TI  - [The risk for recurrent pulmonary tuberculosis in dispensary registration group
      III patients].
AB  - A statistical method was used to specify the significance of the most commonly
      encountered risk factors for recurrent pulmonary tuberculosis. Among others, 10
      factors that substantially influenced the development of an early recurrence were
      identified. These are distributed as follows: medical factors, such as
      comorbidity, the undulating course of a tuberculous process, a contact with a
      tuberculosis patient, an ineffective basic course of therapy for the underlying
      disease, intercurrent diseases, a decay phase, major and minor residual changes.
      Social risk factors were fewer; however, they also had a great influence--the
      unemployed and prisoners. A combination of 4 significant signs or more was of
      significance to the development of an early recurrence; in case of more than 2
      risk factors, the likelihood of a recurrence proved to be insignificant (p <
      0.05).

PMID- 18080530
TI  - [Relationship of the course of nephrotuberculosis in patients to various
      combinations of genetic markers].
AB  - To examine the body's responsiveness in different forms of nepthrotuberculosis,
      237 patients underwent comprehensive clinical laboratory studies. To reveal
      various combinations of genetic markers, the authors determine the phenotypes of
      haptoglobin, the activity of red blood cell glucose-6-phosphate dehydrogenase,
      the type of inactivation of isonicotinic acid hydrazide. According to the
      combinations of a complex of these genetic markers, the authors identified 4
      combinations: poor, good, relatively poor, and relatively good. The studies
      indicated the high incidence of common forms of nephrotuberculosis in subjects
      with poor and relatively poor combinations of genetic markers. The determination
      of various chronic renal failure-associated combinations of genetic markers may
      be used to identify risk groups for this disease.

PMID- 18080531
TI  - [Results of surgical treatment in patients with pulmonary tuberculosis].
AB  - The results of examination and treatment were analyzed in 647 patients operated
      on for pulmonary tuberculoma (PT) in 1990-2004. A pathological lung process was
      revealed in 47.0 +/- 0.3% cases on referral and in 53.0 +/- 0.3% at prophylactic
      fluorography. There were 157 (24.3 +/- 0.2%) bacteria-isolating patients; of them
      39 (24.8 +/- 0.4%) had drug-resistant Mycobacterium tuberculosis. With changes
      being revealed in the lung, the clinical diagnosis of PT was initially diagnosed
      in 161 (24.9 +/- 0.2%) patients. Infiltrative pulmonary tuberculosis was
      diagnosed in most cases (353 patients or 54.6 +/- 0.3%) and transformation of the
      process to a tuberculoma was noted during further treatment. A total of 647
      patients underwent 653 operations. The absolute majority of operations (n = 546
      or 83.6 +/- 0.4%) was represented by partial (or economic) lung resections. On
      pathohistological study, single and multiple tuberculomas were diagnosed in 364
      (55.7 +/- 0.3%) and 289 (44.3 +/- 0.3%) patients, respectively. The tuberculomas
      were in the phase of decay and contamination in 425 (65.1 +/- 65.1 +/- 0.3%) and
      311 (47.6 +/- 0.3%) patients, respectively. Postoperative complications were
      recorded in 36 (5.5 +/- 0.1%) patients. The efficiency of surgical treatment was
      99.7% (0.15 +/- 0.02% mortality) and 92.1% in the immediate and postoperative
      periods, respectively.

PMID- 18080532
TI  - [Experience with small-volume plasmapheresis used in the correction of hemostatic
      disorders in patients with progressive destructive pulmonary tuberculosis].
AB  - Pulmonary tuberculosis may result from a complex of the phenomena predisposing to
      impaired blood coagulation. The purpose of the investigation was to study the
      efficiency of small-volume plasmapheresis in the correction of hemostatic
      disorders in patients with progressive destructive pulmonary tuberculosis. The
      results of examination and treatment were analyzed in 112 patients aged 18 to 65
      years who had progressive destructive pulmonary tuberculosis treated at the
      Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences,
      in 1994 to 2004. The patients were divided into groups: Group 1 (basic)--43
      subjects receiving the standard therapy supplemented by 4 small-volume
      plasmapheresis sessions every 2 days and comparison groups: 2A--36 patients
      receiving 2 plasmapheresis sessions at a week interval and 2B--33 patients being
      on the standard therapy alone. In the presence of endogenous intoxication, the
      patients with disseminated and complicated fibrocavernous tuberculosis were
      ascertained to develop blood coagulative disorders typical of grades 1-2 chronic
      disseminated intravascular coagulation (DIC). The use of small-volume
      plasmapheresis in combination with antiaggregatory and anticoagulant therapy in
      patients with disseminated and complicated fibrocavernous pulmonary tuberculosis
      had a beneficial effect on the blood aggregation controlling system positive
      impact, prevented DIC progression, promoted improvement of blood rheological
      properties. With the standard therapy (including double plasmapheresis at a week
      interval), positive hemostatic changes were absent throughout the preoperative
      period.

PMID- 18080534
TI  - [Organization of antituberculosis care at a municipal level].

PMID- 18080533
TI  - [Study of DC-SIGN gene polymorphism in patients infected with Mycobacterium
      Tuberculosis strains of different genotypes in the Irkutsk Region].
AB  - Polymorphism of the promoter of DC-SIGN gene in Caucasians was studied at
      positions -336A/G and -871/G in 134 patients with pulmonary tuberculosis and 112
      healthy individuals, who lived in the Irkutsk Region, Eastern Siberia. In 90
      patients from the patient cohort M. tuberculosis DNA was isolated and
      investigated using the MIRU-VNTR typing test by 12 loci. Comparison of DC-SIGN
      gene polymorphism in patients with tuberculosis and healthy controls revealed no
      significant differences in loci -336A/ G and -871A/G. Analysis of MIRU-VNTR
      patterns identified 50 unique profiles, among which there were genotypes of the
      families Beijing, T. LAM, Haarlem, "Ural" (Haarlem 4) and X. Among 90 MIRU-VNTR
      genotypes, 42 profiles belonged to the Beijing family. Moreover, the minimum
      spanning tree (MST) test revealed a number of Beijing-like strains. The genotypes
      of the subjects affected with Beijing and Beijing-like strains and those affected
      with the strains of other families (non-Beijing) were compared. A significance
      reduction was found in the incidence of the -336G genotype among the subjects
      affected with Beijing strains versus those infected with non-Beijing strains at a
      frequency of 0.09 and 0.24, respectively (chi2 = 7.64; p = 0.006; OR = 2.7; 95%
      CI 1.1-6.1).

PMID- 18080535
TI  - Expanding generality of surface-enhanced Raman spectroscopy with borrowing SERS
      activity strategy.
AB  - Surface-enhanced Raman scattering (SERS) was discovered three decades ago and has
      gone through a tortuous pathway to develop into a powerful diagnostic technique.
      Recently, the lack of substrate, surface and molecular generalities of SERS has
      been circumvented to a large extent by devising and utilizing various
      nanostructures by many groups including ours. This article aims to present our
      recent approaches of utilizing the borrowing SERS activity strategy mainly
      through constructing two types of nanostructures. The first nanostructure is
      chemically synthesized Au nanoparticles coated with ultra-thin shells (ca. one to
      ten atomic layers) of various transition metals, e.g., Pt, Pd, Ni and Co,
      respectively. Boosted by the long-range effect of the enhanced electromagnetic
      (EM) field generated by the highly SERS-active Au core, the originally low
      surface enhancement of the transition metal can be substantially improved giving
      total enhancement factors up to 10(4)-10(5). It allows us to obtain the Raman
      spectra of surface water, having small Raman cross-section, on several transition
      metals for the first time. To expand the surface generality of SERS, tip-enhanced
      Raman spectroscopy (TERS) has been employed. With TERS, a nanogap can be formed
      controllably between an atomically flat metal surface and the tip with an
      optimized shape, within which the enhanced EM field from the tip can be coupled
      (borrowed) effectively. Therefore, one can obtain surface Raman signals (TERS
      signals) from adsorbed species at Au(110), Au(111) and, more importantly, Pt(l10)
      surfaces. The enhancement factor achieved on these single crystal surfaces can be
      up to 106, especially with a very high spatial resolution down to about 14 nm. To
      fully accomplish the borrowing strategy from different nanostructures and to
      explain the experimental observations, a three-dimensional finite-difference time
      domain method was used to calculate and evaluate the local EM field on the core
      shell nanoparticle surfaces and the TERS tips. Finally, prospects and further
      developments of this valuable strategy are briefly discussed with emphasis on the
      emerging experimental methodologies.

PMID- 18080536
TI  - Fluoride-responsive organogelator based on oxalamide-derived anthraquinone.
AB  - Anthraquinone derived oxalamide gelator 1 forms with aromatic solvents and
      alcohols very stable gels which selectively respond to the presence of fluoride
      anion by colour change and/or gel-to-sol transition.

PMID- 18080537
TI  - Polymorphism of (S)-triphenylglycol: kinetic dependent transformation of a new
      multipolymorphic system.
AB  - The appearance of six new polymorphic forms of (S)-triphenylglycol and the
      kinetically dependent transformation observed by DSC by means of quenching from
      the melt are reported.

PMID- 18080538
TI  - Solvothermal vs. bench-top reactions: control over the formation of discrete
      complexes and coordination polymers.
AB  - The formation of discrete complexes [M(mcoe)2S2] (M = Cu, Ni; S = MeOH, H2O) vs.
      a nitroso-bridged ferromagnetically-coupled Cu(II) coordination polymer
      [Cu(mcoe)2] is influenced by the use of solvothermal reaction conditions.

PMID- 18080539
TI  - Amplified electrochemical detection of DNA through the aggregation of Au
      nanoparticles on electrodes and the incorporation of methylene blue into the DNA
      crosslinked structure.
AB  - The amplified electrochemical sensing of DNA is accomplished by the analyte
      induced aggregation of nucleic acid-functionalized Au nanoparticles, deposition
      of the aggregates on a thiolated monolayer-functionalized electrode, and the
      voltammetric analysis of the redox-active methylene blue intercalated in the
      nucleic acid duplexes associated with the aggregates.

PMID- 18080540
TI  - Profiting from nature: macroporous copper with superior mechanical properties.
AB  - Macroporous copper with a complex hyperbolic morphology and superior mechanical
      properties was produced by replicating the remarkable form of a sea urchin
      skeletal plate using templated electrochemical deposition.

PMID- 18080541
TI  - Pseudo-tetrablock copolymers with ethylene and a functionalized comonomer.
AB  - Pseudo-tetrablock copolymers comprised of ethylene and 5-norbomen-2-yl acetate
      (1), were synthesized using the initiator system (L(i)Pr2)Ni(eta1
      CH2Ph)(PMe3)(2)[(L(i)Pr2) = N-(2,6-diisopropylphenyl)-2-(2,6
      diisopropylphenylimino)propanamide] and 2.5 equivalents of Ni(COD)2 [bis(1,5
      cyclooctadiene) nickel.

PMID- 18080542
TI  - Silica nanoparticle assisted DNA assays for optical signal amplification of
      conjugated polymer based fluorescent sensors.
AB  - A cationic conjugated polymer provided over 110-fold signal amplification for
      silica nanoparticle based assays, which allow detection of target DNAs at a
      concentration of 10 pM with a standard fluorometer.

PMID- 18080543
TI  - A luminescent multicomponent species made of fullerene and Ir(III)
      cyclometallated subunits.
AB  - The first system containing a luminescent Ir(m) cyclometallated species and a
      functionalized C60 unit has been prepared; triplet-triplet energy transfer from
      the Ir-based MLCT state to the C60 triplet state occurs, leading to
      phosphorescence (lifetime, 4.8 ms) of the derivatized-C60 at 77 K.

PMID- 18080544
TI  - Macropolyhedral boron-containing cluster chemistry. The unique nido-five-vertex
      <B2>-nido-ten-vertex conjuncto structure of [(eta5-C5Me5)2Rh2B11H15] via an
      unexpected cluster-dismantling.
AB  - B16H20 and [RhCl2(eta5-C5Me5)]2 with tmnd give [(eta5-C5Me5)2Rh2B11H15], which
      has an unprecedented thirteen-vertex macropolyhedral cluster core based on a nido
      ten-vertex {MB9} subcluster and a nido five-vertex {MB4} subcluster fused with
      their open-face {B2} edges in common.

PMID- 18080545
TI  - Continuous catalytic "one-pot" multi-step synthesis of 2-ethylhexanal from
      crotonaldehyde.
AB  - 2-ethylhexanal is synthesized directly from crotonaldehyde over a bifunctional
      acidic resin-supported palladium catalyst via hydrogenation and aldol
      condensation in supercritical CO2.

PMID- 18080546
TI  - A biaryl cross-coupling strategy for functionalisation of benzocrown ethers.
AB  - Preparation of (di)benzocrown-substituted aryl-zinc or -boron reagents and their
      palladium-catalysed cross-coupling with functionalised aryl halides is described
      for convenient synthesis of novel crown ether systems.

PMID- 18080547
TI  - Preparation of 2-deoxy-2-C-p-tolylsulfonyl-beta-D-glucopyranosyl p-tolylsulfones
      having non-chair conformation and their elimination reactions.
AB  - When the title sulfones, which have non-chair conformations, were stirred with
      silica gel, elimination of sulfinic acid occurred to give a 1-enitol derivative,
      if the hydroxyl group at C-6 was protected, whereas such an elimination did not
      proceed if the hydroxy group was free.

PMID- 18080548
TI  - Simultaneous anomalous reflection and quartz-crystal microbalance measurements of
      protein bindings on a gold surface.
AB  - Protein bindings onto a gold surface were detected simultaneously by QCM (delta
      F(water)) and anomalous reflection (deltaR) of gold on the same surface in
      aqueous solutions; the obtained delta F(water)/deltaR values correlated with
      surface areas and viscosity of proteins.

PMID- 18080549
TI  - Rhodium-catalysed addition reaction of aryl- and alkenylboronic acids to
      isocyanates.
AB  - The addition reaction of aryl- and alkenylboronic acids to isocyanates is
      catalysed by a rhodium(I) complex, affording secondary amides under mild
      conditions.

PMID- 18080550
TI  - A new diastereoselective aza-allyl conjugate addition-Michael addition-ring
      closure reaction sequence and its application in the construction of six
      contiguous stereogenic centres.
AB  - Reaction of the sodium anion of (S)-N-(alpha-methylbenzyl)allylamine with two
      equivalents of tert-butyl cinnamate results in a remarkable tandem aza-allyl
      conjugate addition-Michael addition-ring closure reaction, resulting in a chiral
      aminocyclohexane containing six new vicinal stereogenic centres with excellent
      levels of stereocontrol.

PMID- 18080551
TI  - Effect of fluorine on palladium-catalyzed cross-coupling reactions of aryl
      bromides with trifluoromethyl aryl ketones via difluoroenol silyl or
      monofluoroenol silyl ethers.
AB  - Palladium-catalyzed cross-coupling reactions of alpha-aryl-beta,beta-difluoroenol
      silyl and alpha-aryl-beta-fluoroenol silyl ethers with aryl bromides proceed
      smoothly with good functional compatibility.

PMID- 18080552
TI  - An asymmetric S(N)Ar reaction using the molecular chirality in a crystal.
AB  - An asymmetric S(N)Ar reaction was performed by using molecular chirality
      generated and amplified by the spontaneous crystallization of achiral
      naphthamides; the chirality was retained in a cold solution, caused by slow
      racemization, and was transferred to stable axially chiral materials with high
      enantiomeric excesses.

PMID- 18080553
TI  - [Study on the distribution of prevalence of hypercholesterolemia and borderline
      high cholesterol in Chinese adults].
AB  - OBJECTIVE: To study the distribution of prevalence on hypercholesterolemia and
      borderline high cholesterol of Chinese residents aged 20 years and above.
      METHODS: To detect the total fasting plasma cholesterol in 48 299 subjects among
      20 year-olds and above. RESULTS: Within a certain age range, the prevalence of
      both hypercholesterolemia and borderline high cholesterol increased with age, but
      there was a decreasing trend after 60-years of age in some regions. The
      prevalence of hypercholesterolemia increased to 12.53% in over 70 year-olds group
      from 1.36% in urban 20-year-olds, and increased to 5.15% from 60-year-olds group
      comparing to 0.98% of the 20-year-old group in rural areas. When comparing to the
      20-year-old age group, the prevalence of borderline high cholesterol of the 70
      age group in urban and rural increased by 4.4 and 4.2 times, respectively. The
      prevalence of hypercholesterolemia in each age group in urban were higher than
      that of in rural areas. In Rural I, it was higher than that of in Rural II ,
      Rural III and Rural IV. The prevalence rates of both hypercholesterolemia and
      borderline high cholesterol of the males in the less than 50 year-olds group were
      higher than that in females, which was quite different from the group older than
      50 years of age. As to borderline high cholesterol, similar result was also
      noticed. CONCLUSION: Within a certain age range, there was a trend that the
      prevalence of both hypercholesterolemia and borderline high cholesterol increased
      with age and related to regions which were classified by economic status. A
      distinct difference between males and females also existed.

PMID- 18080554
TI  - [Study on the relation between anthropometric parameters and lipids profiles].
AB  - OBJECTIVE: To study the relations between anthropometric parameters [body mass
      index (BMI), percent of body fat, waist circumference] and blood lipids of urban
      children in Beijing and to compare the ability of prediction effect of waist
      circumference, percent body fat and BMI on lipid profiles. METHODS: 852 children
      aged 9-10 were recruited with multi-stage sampling. Serum lipids of children were
      measured using automatic biochemical instrument. Fisher's exact test, trend test
      and median regression were used to analyze the data from 847 subjects with valid
      information. RESULTS: (1)With the rise of the BMI, percent body fat and waist
      circumference, total triglycerides (TG), total cholesterol (TC) and low density
      lipoprotein choleasterol (LDL-C) showed increasing trends while high density
      lipoprotein choleasterol (HDL-C) had a decreasing trend(P < 0.01). (2)TG was
      mainly influenced by waist circumference (t = 6.86), sex (t = 3.96) and percent
      of body fat (t = 1.85); TC was influenced by percent of body fat (t = 5.31); LDL
      C was influenced by waist circumference (t = 4.65), height (t = -2.79) and
      percent age of body fat (t = 2.77); HDL-C was influenced by waist circumference
      (t = -12.24), sex (1= -5.83). CONCLUSION: With the aggravation of children's
      fatness (BMI, WC and PBF), serum lipids would increase and WC seemed to be the
      best predictor for lipids among BMI, WC and PBF.

PMID- 18080555
TI  - [Study on the level of tobacco-generated smoke in several restautants and bars in
      Beijing, China].
AB  - OBJECTIVE: To investigate the current smoking regulations and their impacts on
      the environmental tobacco smoke (ETS) levels inside restaurants and bars in
      Beijing. METHODS: Telephone survey was used to investigate the smoking
      regulations. TSI Sidepak AM510 was used to measure the level of fine particles
      less than 2.5 microns in diameter (PM2.5) in restaurants and bars. Analysis of
      variance and non-parametric rank tests were used to examine the association
      between indoor and outdoor PM2.5 levels and (1) smoking regulations; and (2)
      types of restaurants and bars. RESULTS: Of the 305 restaurants and bars surveyed,
      27.9% had complete or partial smoking prohibiting rules. The average indoor
      PM2.5, level of the 92 restaurants and bars was 253.08 microg/m3 , 102.37% higher
      than the outdoor level. The average indoor and outdoor PM2.5 levels in the
      restaurants and bars with smoking ban regulations were 93.10 microg/m3 and 110.33
      microg/m3 whole 289.34 microg/m3 and 128.40 microg/m3 in those without,
      respectively. The average indoor and outdoor PM2.5 levels of bars were 413.46
      microg/m3 and 190.62 microg/m3, respectively, while in the western fast-food
      restaurants, they were 83.86 microg/m3 and 104.77 microg/m3, respectively. The
      outdoor PM2.5 levels were higher than the indoor levels in different classes of
      restaurants and bars. Furthermore, there was a significant positive correlation
      between PM2.5 levels and the number of smokers per cube meters (r = 0.47, P <
      0.001). CONCLUSION: Smoking regulations could effectively reduce the ETS level in
      restaurants and bars.

PMID- 18080556
TI  - [Factors in relation to repeated abortions among unmarried young people in
      Shanghai].
AB  - OBJECTIVE: To study the factors related to repeated abortions among unmarried
      young people, and to standardize the services as informed choice counseling and
      post abortion, and to reduce the repeated abortion rate. METHODS: A cross
      sectional survey using anonymous questionnaire was conducted among unmarried
      young women who requested termination of early pregnancy in 10 hospitals in
      Shanghai. RESULTS: 2343 subjects responded to the questionnaires. Results showed
      that the repeated abortion rate was 38.5%, repeated abortion rate within 1 year
      was 23.5%, and the high risk factors of abortion accounted for 40.2% . Subjects
      who were older than 19, unemployed, with poor education background, cohabitating
      and boyfriends being elder were more likely to have repeated abortions (OR > 1).
      Subjects who did not change boyfriend or use no contraception were more likely to
      have repeated abortions 1 year after abortion (OR > 1). CONCLUSION: No reliable
      contraception used after abortion seemed to be the main reason for repeated
      unwanted pregnancy. Being socially disadvantaged women such as unemployed or with
      poor education background, meanwhile cohabitating with boyfriends or boyfriends
      being elder etc. they should be viewed as the key population for intervention.
      Male involvement and reliable contraceptive methods use among young people should
      be emphasized as key steps for intervention. 1 year after abortion fell into the
      key period for intervention. Reinforcement on factors including: training for
      service providers to improve their skills, setting up standard technical process
      and monitoring systems to carry out the basic principle of 'Informed Choice', and
      widely launching post-coital contraception programs including emergency
      contraception, luteal phase contraception and menstrual induction should be
      stressed.

PMID- 18080557
TI  - [Analysis on factors affecting maternal mortality in China].
AB  - OBJECTIVE: To investigate the factors related to maternal mortality rate in 1000
      counties of projects on reducing maternal mortality rate (MMR) and eliminating
      tetanus neonates in China, 2003. METHODS: Study on the association was performed
      using data on average income per capita, hospital delivery rate and MMR. RESULTS:
      Data showed that income per capita and hospital delivery rate had strong
      association with MMR. MMR for women with income less than 1000 Chinese Yuan per
      capita was 100.9 per 100 000 live births, and with income over 2000 Yuan per
      capita was 61.8 per 100 000 live births. MMR was 107.2 per 100 000 live births
      for women with hospital delivery rate less than 50%, and 54.1 per 100 000 live
      births with hospital delivery rate over 75%. The hospital delivery rate was less
      than 50% in the counties with income less than 1000 Yuan per capita, and over 75%
      with income over 2000 Yuan per capita. Only 19.1% of the counties with income
      less than 1000 Yuan per capita and 66.7% over 2000 Yuan per capita reached 75%
      hospital delivery rate. CONCLUSION: MMR and hospital delivery rate were affected
      by economic level of individuals. MMR seemed inversely proportional to income per
      capita and hospital delivery rate. The hospital delivery rate in 1000 counties
      was closely associated with income per capita. MMR could be reduced by enhancing
      hospital delivery rate.

PMID- 18080558
TI  - [Epidemiological study on 38 418 syphilis cases during pregnancy].
AB  - OBJECTIVE: To explore the prevalence of syphilis and risk factors on pregnant
      women in Fujian province. METHODS: From July 1st, 2004 to June 30th, 2006,
      epidemiologic methods as questionnaires to fill in and rapid plasma reagent
      testing (RPR) were performed. Pregnant women with positive RPR test and then were
      confirmed by treponema pallidum test (TP). Intervention was provided to the
      pregnant women who were followed up to the postpartum periods. Results were
      compared during the peri-neonatal stage between syphilis-infected and non
      infected women. Factors which were relative to syphilis infection were analyzed
      by simple and then further logistic regression analysis. RESULTS: There were 38
      418 pregnant women under study, of whom 772 were confirmed including 60 who were
      still pregnant. The prevalence of syphilis during pregnancy was 1.85% (712/38
      418), with mostly underlying syphilis which played an important role during the
      neonatal stage. Main risk factors to have been found as: women's occupation,
      cultural background, place of living, husband's occupation, family income, having
      sexually transmitted disease(STD) infection. The prognosis of peri-neonatal stage
      was worse if the mother was having blood RPR test positive. Mortality of peri
      neonatal, preterm birth rate and low-birth weight rate were found also higher
      among mothers when RPR was positive (P < 0.01). CONCLUSION: The prevalence of
      syphilis in Fujian province was going up yearly. 8 factors including women's
      occupation, cultural background, place of living, received poor health education,
      having multiple sexual partners, husband's occupation, family income and having
      STD were main risk factors in the province, the mother's status of syphilis
      infection would strongly relate to the peri-neonatal stage of pregnancy.

PMID- 18080559
TI  - [Surveillance program set for influenza A virus (H1N1) in children in Taiyuan,
      China, 2005-2006].
AB  - OBJECTIVE: To study the epidemic situation and dominant strain of influenza in
      children with acute respiratory infection (ARI) during Flu season from Oct. 2005
      to Mar. 2006 in Taiyuan. METHODS: Madin-darby canine kidney (MDCK) cell culture
      and hemagglutination inhibition (HI) assay were used to isolate and identify type
      A influenza viruses (H1N1 and H3N2) and B influenza viruses from clinical samples
      collected from outpatients who visited the Department of Pediatric because of ARI
      from Oct. 2005 to Mar. 2006. Oct. 2005 and Mar. 2006, we collected 415 blood
      samples from children and adults to detect the influenza virus antibody titers by
      HI test to exclude respiratory diseases. RESULTS: 7 strains of H1N1 were isolated
      from 87 clinical specimens, with a positive rate of H1N1 as 8.04%. Out of 415
      blood samples being collected, the positive rates and the geometric mean titer of
      H1N1 antibody Mar. 2006 were significantly higher in 0-3, 3-7 and 7-18 year-olds
      than Oct.2005. CONCLUSION: H1N1 epidemic influenza did occur among children in
      winter and spring of 2005--2006 in Taiyuan city.

PMID- 18080560
TI  - [Molecular typing of Neisseria meningitidis serogroup C strains with pulsed field
      gel electrophoresis in China].
AB  - OBJECTIVE: To study the characteristics of epidemiology and molecular typing on
      Neisseria meningitidis serogroup C strains associated with outbreaks of Anhui
      province and sporadic cases in China, using pulsed field gel electrophoresis
      (PFGE). METHODS: 212 Neisseria meningitidis serogroup C strains were isolated
      from invasive meningococcal cases, close contacts and healthy carriers, including
      48 strains from Anhui province with 38 strains associated with serogroup C
      outbreaks. PFGE were performed by genomic DNA digestion with Nhe I restriction
      enzyme. The results of PFGE were analyzed by BioNumerics software (Version 4.0,
      Applied Maths BVBA, Belgium). RESULTS: A total number of 212 Neisseria
      meningitidis serogroup C isolates were typed by 43 patterns, named AH1 to AH43.
      In China, AH1 pattern was the major PFGE pattern with 69.3% (n = 147) of all
      strains, distributed in 11 provinces. Three types of PFGE patterns (AH1 to AH3)
      were found in 48 strains from Anhui province, in which, 93.8% (n = 45) belonged
      to AH1. 97.4% (n = 37) of 38 strains associated with serogroup C outbreaks in
      Anhui province showed AH1 pattern. A total of 53 serogroup C strains were
      isolated from invasive meningococcal cases with 67.9% (36/53) of AH pattern.
      71.9% (87/121) of serogroup C strains isolated from contacts of invasive
      meningococcal cases was AH1 pattern and 63.2% (24/38) of the strains from healthy
      carriers showed AH1 pattern. CONCLUSION: By PFGE typing and analysis, AH1 pattern
      of Neisseria meningitidis serogroup C strains was proved to be the main clone
      which causing the outbreaks in Anhui province and might be responsible for the
      sporadic serogroup C meningococcal disease epidemics else where in the country.

PMID- 18080561
TI  - [Study on the epidemiological characteristics of measles in Henan province during
      2004-2006].
AB  - OBJECTIVE: To understand the epidemiological characteristics of measles in Henan
      province during 2004-2006 and to evaluate the quality of measles special report
      system (MSS) in order to provide evidence for strategies and measures development
      for measles prevention and control. METHODS: Data were collected from the
      National Notifiable Disease Report System (NNDRS) and MSS on epidemiological
      characteristics of measles in Henan province during 2004-2006. RESULTS: The
      sensitivity of MSS was lower than that of NNDRS in Henan province during 2004
      2006. The incidence of measles appeared to be 2.54/100 000 in 2004 increased to
      8/100 000 during 2005-2006. The incidence of measles was higher in the central
      part of the province during the recent years with cases concentrated in March to
      May every year. The percentage of cases from age groups < 8 months and 8 months
      to 1 year olds increased yearly. All the cases with no or unclear vaccination
      record took up 77.13%, with 18.23% of the measles cases fell into the floating
      population. CONCLUSION: Improving the 2 doses and timely coverage rate of the
      first dose of measles vaccine strategy was essential for measles control and
      prevention. In order to improve the quality of measles surveillance program, the
      advantage of MSS and NNDRS should be integrated.

PMID- 18080562
TI  - [Study on the pathogens correlated to sexually transmitted diseases in 285 pre
      pubertal girls with vulvovaginitis in Beijing].
AB  - OBJECTIVE: To study the relationship between vulvovaginitis in pre-pubertal girls
      and pathogens as Chlamydia trachomatis (Ct), N. gonorrhoeae (Ng), Mycoplasma,
      Ureaplasma urealyticum (Uu), Mycoplasma hominis (Mh), M. genitalium (Mg), M.
      fermentans (Mf) and M. penetrans (Mpe), as well as to find out the proportion of
      mycoplasma which is correlated to sexually transmitted diseases (STD) and AIDS.
      METHODS Vulvae swab specimens from 285 pre-pubertal girls with vulvovaginitis
      (case group) and 128 healthy girls (control group) were collected and detected by
      nested polymerase chain reaction (nPCR) to identify the existence of pathogens as
      Ct, Ng, Uu, Mh, Mg, Mf and Mpe. nPCR with both high specificity and sensitivity,
      would not be influenced by the amount of pathogens in specimens or inactivated
      during the process of storage or transportation. RESULTS: The rate of detection
      on pathogens was 59.65% in the 285 specimens from case group including 'one kind
      of pathogen in one specimen' as 37.54% and 'two kinds' as 16.84% and 'three
      kinds' as 5.26%. However, in the 128 specimens from control group, the detectable
      rate of pathogen was 6.25%. Relationships were found between Ng (P < 0.01), Ct (P
      < 0.01), Uu (P < 0.01), Mg (P < 0.01), Mf (P < 0.05), Mpe (P < 0.01) and
      vulvovaginitis in pre-pubertal girls. In control group the pathogens were
      detected from 7 specimens including 5 Uu and 2 Mh. CONCLUSION: Some of the
      pathogens were correlated to STD and were important in causing vulvovaginitis in
      pre-pubertal girls. Vulvovaginitis might have been caused by more than one kind
      of pathogen in pre-pubertal girls. The locations of Mg, Mf and Ng in outer
      genital tracts were correlated to seasonal change. Macrolide seemed to be quite
      effective clinically in treating urogenital tract infection caused by mycoplasma
      and Ct.

PMID- 18080563
TI  - [Development and application of real-time polymerase chain reaction to detect
      Vibrio cholerae O1 and O139 in river water].
AB  - OBJECTIVE: To develop a real-time SYBR Green polymerase chain reaction (PCR) for
      detection of Vibrio cholerae serogroups O1 and O139, and to evaluate its
      reliability through detection of estuary water samples. METHODS: O antigen rfb
      genes specific for O1 and O139 were used for the design of PCR primers. The real
      time SYBR Green PCR system in detecting O1 and O139 specific rfb genes in one
      tube was developed, and its sensitivity, specificity and reproducibility were
      evaluated. The ability of the real-time PCR in detection of estuary water samples
      was compared with the routine PCR and bacteria isolation. RESULTS: The
      amplification of O1 or O139 specific target gene could be detected according to
      the melt curve temperature of amplicons. No amplification was observed in the
      templates of other 10 non-cholerae vibrios. When comparing to the real-time PCR
      to bacteria isolation in detection of 524 estuary water samples, it showed high
      sensitivity, plus also positive in real-time PCR detection among all the samples
      in which bacteria of O1 or O139 were isolated. CONCLUSION: The real-time SYBR
      Green PCR could be used as the first step of rapid environment screen of V.
      cholerae in water samples thus might enhance the efficiency of isolation in
      screening of large amount of water samples.

PMID- 18080564
TI  - [Establishment of standardized method for pulsed-field gel electrophoresis on
      Leptospira interrogans and analysis on their patterns].
AB  - OBJECTIVE: To establish a standardized operation procedure for pulsed-field gel
      electrophoresis (PFGE) on Leptospira interrogans as well as a figure digital
      database to develop the Chinese representative reference strains. METHODS: Under
      the characteristics of strains and referring to the other SOPs of PFGE on
      pathogens provided by CDC and PulseNet Asia Pacific, genomic chromosome DNA
      purification, restriction endonuclease digestion and the parameters for running
      PFGE were optimized. RESULTS: Not I digestion patterns of leptospiral genome for
      the Chinese representative strains were established and partial isolates of
      serogroup icterohaemorrhagiae from the leptospirosis surveillance in Sichuan and
      Anhui provinces were analyzed by PFGE. Results showed that each of all the 15
      Chinese representative strains had a unique pattern. 91.67% (22/24) of the 24
      isolates identified as serogroup icterohaemorrhagiae matched to the map of the
      reference strain 56601 (serogroup icterohaemorrhagiae serovar lai). CONCLUSION:
      The PFGE figures were clear with high resolution and the fragments were equally
      distributed by this standardized operating procedure so as to reveal the
      molecular-genetic characteristics of Leptospira interrogans. The patterns had
      high relativity with the serological identification and seemed to be very
      important for genetic analysis of strains in studying the outbreak of
      leptospirosis.

PMID- 18080565
TI  - [Study on the location of membrane and detection of antibody in the sera of genus
      specific antigen LipL41s in patients with Leptospira interrogans].
AB  - OBJECTIVE: To determine the location on outer envelope and natural antibody
      response and types of genus-specific lipoprotein antigen LipL41s in patients with
      Leptospira interrogans. METHODS: Microscope agglutination test (MAT) was used to
      examine leptospirosis patients' serum samples from Sichuan area, China. Ni-NTA
      affinity chromatography was performed to extract the target recombinant rLipL41/1
      and rLipL41/2 products that expressed under inducement of IPTG. Western blot
      assay was performed to detect the immunoreactivity between the sera from the
      patients infected with different serogroups of L. interrogans and rLipL41s.
      Immune aurosol electron microscopy was selected to locate the position of LipL41s
      on leptospiral envelope. ELISA based on rLipL41s was established to confirm the
      level and types of specific antibody. RESULTS: L. interrogans serogroup
      icterohaemorrhagiae remained to be the most dominant leptospiral serogroup in
      Sichuan area. All the sera from patients infected with different serogroups of L.
      interrogans could efficiently recognize the LipL41s which were the protein
      molecular that located on the external surface of leptospiral envelope. In the
      156 serum samples from MAT positive leptospirosis patients, the positive rates
      for rLipL41/1 or rLipL41/2 specific IgM appeared to be 84.6%-87.8% and 78.2%
      83.3%, respectively, while for rLipL41/1 or rLipL41/2 specific IgG they were
      69.2%-81.4% and 75.0%-80.1%, respectively. CONCLUSION: LipL41s were the
      leptospiral superficial protein antigen of L. interrogans. Both the LipL41/1 and
      LipL41/2 could induce serum antibodies IgM and IgG with extensive antigenic-cross
      reaction during natural infection of L. interrogans in general populations.
      Hence, rLipL41/1 or rLipL41/2 could be used as the antigen candidate for
      developing universal genetic engineering vaccine and detection kit.

PMID- 18080566
TI  - [Identification and typing for adenovirus by multiplex nest-PCR].
AB  - OBJECTIVE: To develop a rapid, sensitive and specific method in identifying and
      typing on adenovirus from clinical specimens. METHODS: Primers were designed
      using hexon gene of adenovirus as target. One primer pair was designed as
      universal primers for amplifying a 1278 bp gene fragment located at the hexon
      gene of adenovirus from all types. Four primer pairs located within the region of
      this 1278 bp were specifically designed for amplifying types 3, 7, 11 and 21 of
      adenoviruses, which were used for multiplex nest-PCR in a single tube. The
      products from this multiplex nest-PCR were 502 bp (for type 3), 311 bp (for type
      7), 880 bp (for type 11) and 237 bp (for type 21), respectively. Type of the
      adenovirus tested could then be determined after agarose electrophoresis analysis
      of the PCR products. RESULTS: PCR products with predicted sizes were visualized
      in the agarose gel for prototype strains of adenovirus types 3, 7, 11 and 21, but
      not for other respiratory viruses, indicating that the technique was specific
      without cross reaction with other viruses. Out of the 118 clinical specimens
      which had been proved to be adenovirus positive by tissue culture and/or
      immunofluerescence assay, 76 belonged to adenovirus type 3 (76/118, 64.4%), 37 to
      adenovirus type 7 (37/118, 31.4%), 3 to adenovirus type 11 (3/118, 2.5%) but no
      adenovirus type 21 was detected. Two of the 118 positive specimens which were
      positive by both tissue culture and immunofluerescence could not be identified,
      suggesting that these 2 strains (1.7%) were with the types other than types 3, 7,
      11 and 21. Out of the 33 specimens which were negative by both tissue culture and
      immunofluerescence, 3 showed positive by this multiplex PCR (2 of type 3 and 1 of
      type 7), suggesting this method was more sensitive than tissue culture and
      immunofluerescence. CONCLUSION: This multiplex nest-PCR method had the benefit of
      rapid,sensitive and specific nature so could be used for identifying types of
      adenoviruses in the clinical specimens.

PMID- 18080567
TI  - [Study on the genotype of Mycobacterium tuberculosis isolates from hospitals in
      Tianjin].
AB  - OBJECTIVE: To explore the characteristics on molecular epidemiology of
      Mycobacterium tuberculosis isolates from hospitals in Tianjin area. METHODS: One
      hundred M. tuberculosis isolated strains were collected in succession from August
      16th-December 25th, 2005 in Tianjin Haihe Hospital and genotyped by spoligotyping
      and multiple locus variable number-tandem repeat(VNTR). Data was analyzed by
      cluster software. Based on the concept of Beijing lineage, it was determinate two
      sub-groups: atypical Beijing strains and W strain/typical family strains by
      multiplex and real-time PCR. The associations of subgroups with drug resistance
      and age were assessed by the chi2 test. RESULTS: 96 M. tuberculosis strains were
      genotyped in which 91.7% (88/96) strains belonged to Beijing genotype (including
      3 Beijing-like strains) by spoligtyping. VNTR typing could differentiate 60
      genotypes among the 88 Beijing genotype strains. 93.2% of the Beijing lineage M.
      tuberculosis strains of this study belonged to W strain/typical Beijing family
      strains (82/88). No statistically significant differences were observed in the
      proportions of the two sub-groups in patients of different age, or drug
      resistance (P > 0.05). CONCLUSION: The M. tuberculosis Beijing genotype strains
      were dominated on tuberculosis hospital patients of Tianjin area. The
      discriminatory power of VNTR typing was higher than that of spoligtyping. The two
      sub-groups of Beijing lineage had been prevalent in Tianjin, however W
      strain/typical Beijing family strains were of preponderance.

PMID- 18080568
TI  - [Characterization of qnr gene for plasmid-mediated quionlone resistance].
AB  - OBJECTIVE: To explore the distribution of qnr gene and broad spectrum p-lactamase
      (ESBLs) gene in gram-negative bacteria which were isolated from our hospital
      patients. METHODS: qnr gene in nonrepetitive 129 isolates of Escherichia coli, 10
      isolates of Enterobacter cloacac and 29 isolates of K. pneunoniae were detected
      by polymerase chain reaction (PCR). For qnr gene positive strains, int I, SHV-1,
      TEM-1, CTX-M, OXA-I , OXA-II , OXA-III, DHA and EBC genes were examined. Plasmid
      conjugatable test was applied to examine whether qnr gene was located in
      conjugate plasmid and ERIC-PCR was carried out for DNA homologous analysis. ESBLs
      detection (according to phenotypic confirmatory test based on National Committee
      for Clinical Laboratory Standards criteria) and susceptibility test to 16
      antibiotics were also performed. RESULTS: qnr gene was found in 6 clinical
      isolates including 5 strain of E. coli and one strain of E. cloacac, but qnr gene
      was undetectable in K. pneunoniae isolates. The 6 clinical isolates were
      suspectible to imipenem but resistance to some other drugs while only 2 isolates
      of E. coli were susceptible to quinolone. Among the 6 qnr gene-positive strains,
      all of them belonged to I type integron-positive isolates, 4 isolates of them
      were TEM-1 producing strains,with only one isolate was OXA-III gene producing
      strain, and 2 isolates of them were EBC producing strains. Most of them were with
      2 ESBLs gene if not more. qnr gene was on transferable plasmids which could be
      disseminated by clone. CONCLUSION: In Wuhan city, the prevalence of qnr was
      confirmed. qnr gene were found with some ESBLs gene in the same strains, and qnr
      gene in suspect strains. The transmission of qnr gene producing strains could be
      mediated by transferable plasmids or clone, forcing us to make intensive
      investigation and take effective control measures.

PMID- 18080569
TI  - [Clinical-epidemiological study on newborn's apgar score in 'one minute' and
      relevant factors].
AB  - OBJECTIVE: To study the newborn's Apgar score in 'one minute' and relevant
      factors. METHODS: One year inpatient woman from a Maternal and Child Health
      Hospital of Anhui province were selected by cluster sampling method and newborn
      asphyxia situation was investigated using Apgar score and self-designed
      questionnaire. RESULTS: The Apgar score in 'one minute' which marking 8 to 10, 4
      to 7 and 0 to 3 were found in 1875 (73.78%), 426 (16.77%) and 240 infants (9.45%)
      respectively. The average Apgar score in 'one minute' and five minutes were (7.69
      +/- 2.27) and (9.01 +/- 1.89) respectively, The Apgar score in 'one minute' was
      significantly correlated with that of five minutes (Pearson coefficient
      correlation r = 0.841, P = 0.00). Ordinal regression analysis revealed that
      parturient age (OR = 1.04), being farmer (OR = 2.22), parity (OR = 1.26),
      assistant vaginal delivery (OR = 4.93), caesarean section (OR = 1.95), pregnancy
      induced hypertension syndrome (OR = 1.42), albuminuria in gestational period (OR
      = 1.44), newborn being male (OR = 1.23), low birth weight (OR = 2.94), inborn
      abnormality (OR = 12.12), premature birth (OR = 1.22) and complications of
      delivery (OR = 5.04) were risk factors while the number of years under study (OR
      = 0.91), prenatal check-up (OR = 0.48), body length of newborn infant (OR = 0.88)
      and single birth (OR = 0.57) were protective factors. CONCLUSION: Apgar score in
      'one minute' of newborn infant was affected by several factors as stated above.
      Health care program in earlier period toward community parturient should be
      strengthened in order to discover and control high risk factors of duration of
      pregnancy in earlier period.

PMID- 18080570
TI  - [Study on the correlation between hypertension and the indexes of vascular
      endothelial function among people living in the community].
AB  - OBJECTIVE: To study the features of hypertension and vessel endothelium
      functional parameter in people living at the community level as well as the risk
      factors of hypertension. Differences of angiotensin II (Ang II ), prostacyclin
      (PGI2) and nitric oxide (NO) among normal group and three hypertension groups
      were also studied. METHODS: By cluster sampling, 1134 adult Han people were
      selected from the residential communities. Medical history was documented and
      measurements of body height, body weight, waist circumference, hip circumference
      and blood pressure were performed. Serum NO levels were determined by cadmium
      reduction method while plasma Ang II and PGI2 concentration were determined by
      radioimmunoassay. SPSS 13.0 was used for data analysis. RESULTS: The total ratio
      of hypertension from people living at the community was 44.5%, with the
      standardized prevalence of hypertension as 15.3%. With the increase of age, the
      prevalence of hypertension also increased. Overweight and obesity seemed to be
      independent risk factors for hypertension. History of smoking and drinking and
      gender did not enter the logistic equation for hypertension. The amount of plasma
      Ang II concentration of the three hypertension groups was significantly lower
      than that in the normal group while the lowest group appeared to from the one
      that hypertension was under control. The NO and PGI2 levels of the two groups
      whose hypertension had been known were significantly higher than in the normal
      group while the difference between the group whose hypertension had not been
      measured and the normal group was not found. CONCLUSION: The prevalence of
      hypertension had been increasing. Control of body weight seemed to be a useful
      way for prevention of hypertension. We assumed that the negative feedback
      regulation of renin-angiotonin-aldosterone system in hypertension patient still
      existed which called for the research on the mechanism of hypertension.

PMID- 18080571
TI  - [Study on the application of Knox method to temporal-spatial cluster for
      infectious diseases].
AB  - OBJECTIVE: Application of Knox method was discussed in exploring temporal-spatial
      cluster for infectious diseases. METHODS: The theory of Knox method was
      introduced in detail. As an example, the temporal-spatial cluster of epidemic
      cerebrospinal meningitis cases from April to May in 2005 was explored in Beijing
      and the statistical process of Knox method was clearly demonstrated with related
      results well interpreted. RESULTS: Only when time and distance threshold values
      were set as 13 days and 29.67 km, potential temporal-spatial cluster could be
      detected in epidemic cerebrospinal meningitis cases. CONCLUSION: According to the
      characteristics of the epidemics, under Knox method, if appropriate threshold
      values of time and distance were chosen, information on temporal-spatial cluster
      of infectious diseases could be obtained. According to the records of different
      time and distance threshold values, the nature of an infectious disease might be
      explored. Thus Knox method could help us to strengthen the early warning system
      on infectious disease control strategy.

PMID- 18080572
TI  - [Estimation of gene-environment interaction regarding partial case-control study
      with missing data on gene information of the controls].
AB  - OBJECTIVE: To discuss the estimation on gene-environment interaction in partial
      case-control studies when gene information of the controls was partly missing.
      METHODS: The results of hot deck multiple imputation and listwise deletion
      analysis were compared when missing data was generated using Monte Carlo method
      in Stata 9.0. RESULTS: Coefficients of environment effect, gene effect and gene
      environment interaction were respectively estimated by means of hot deck multiple
      imputation and listwise deletion when approaching to those complete data with
      missing part less than 50 percent. Both estimated variances of the two methods
      were increasing with the increased proportion of missing data, but the estimated
      variance of hot deck multiple imputation was smaller than the one with listwise
      deletion in each proportion. CONCLUSION: Hot deck imputation could be adopted to
      make full use of existing information to estimate gene-environment interaction in
      the partial case-control study when missing proportion of gene data of controls
      was less than 50 percent so as to increase the precision of the estimation.

PMID- 18080573
TI  - [The impact of incorrectly-measured variables when mixed with precisely measured
      variables on the study of validity in epidemiological research].
AB  - OBJECTIVE: To explore the impact of measurement error on the associated effects
      under the incorrectly-measured variables when mixed with precisely measured
      variables. METHODS: Based on the functions of measurement error, correlation of
      incorrectly-measured predictors and precisely measured explanatory variables,
      number of precisely measured explanatory variables and associated effect, the 'R
      Project for Statistical Computing' method is used to analyze the impact of
      measurement on the validity of a study. RESULTS: Under the scenario that the
      continuous response Y and the continuous explanatory Z are precisely measured but
      the continuous predictor X is incorrectly-measured, when focusing on inference
      about the effect of X on Y, the non-differential measurement error always makes
      the value of estimated effect less than the actual value, and the attenuation
      effect of measurement error more closely worsens the correlation of X and Z.
      Under a misclassification dichotomous predictor X with an additional precisely
      measured explanatory variable Z and focusing on inference about the effect of X
      on Y, the misclassification bias is not only related to the sensitivity and
      specificity of exposure measurement, but also to the correlation between X and Z
      and exposure proportion of X. The attenuation factor (AF) decreases gradually
      with the increasing correlation between X and Z. For instance, in the p = 0.5
      scenario, AF is 1.419, and the estimated effect of dichotomous predictor X on
      continuous response Y is more than the actual effect. When it increases to 0.9,
      AF is 0.474, the estimated effect becomes less than the true effect. CONCLUSION:
      In the studies of the impact of measurement error in linear regression with
      additional precisely measured explanatory variables, the impact of measurement
      error on the associated effect is relatively complex, suggesting that it is
      necessary to control and to assess the measurement error bias in order to
      correctly interpret the results of a study.

PMID- 18080574
TI  - Ask the expert. The key elements involved in the successful implementation of an
      electronic documentation system for trauma nurses.

PMID- 18080575
TI  - A unique approach to inpatient injuries: the trauma triage response.

PMID- 18080576
TI  - Teaching complex trauma care in a curriculum challenges critical thinking and
      clinical judgment--how nurses can help.
AB  - Incorporating complex content into a nursing curriculum presents students with
      the knowledge and thinking skills necessary to enter a career in nursing. A level
      1 trauma center is a prefect environment to advance these thinking skills. Nurses
      act as professional role models and teachers as they clarify and explain their
      thinking to a student. When experienced nurses show invitational behaviors to
      students and share their knowledge with them, they ignite a strong desire within
      the student to progress. Caring, communication, and inclusion are key components
      that synergize the teaching/learning experience. The development of critical
      thinking is a continuous process that is best achieved through collaboration
      between the student, faculty, and professional, experienced nurses.

PMID- 18080577
TI  - A case study of right ventricular rupture in an elderly victim of motor vehicle
      crash: incorporating end-of-life care into trauma nursing.
AB  - Cardiac trauma fatalities occur in 22% of victims of motor vehicle crash. Blunt
      cardiac trauma may result in myocardial rupture. Mechanisms of injury include
      compression, deceleration, laceration, and "hydraulic ram" effect. Diagnosis is
      difficult because of coexisting injuries and the lack of evidence-based
      protocols. Physiological changes in the elderly and the presence of comorbid
      illness result in poor survival rates when myocardial rupture occurs. Trauma
      nurses must be prepared to provide end-of-life care related to the poor outcome
      associated with myocardial rupture. This case study reports a right ventricular
      rupture in an elderly patient involved in a frontal motor vehicle crash.

PMID- 18080578
TI  - Assessment of Ohio's adult and pediatric legislatively mandated prehospital
      trauma triage criteria.
AB  - BACKGROUND: The study objective was to validate prehospital indicators mandated
      by the Ohio legislature. METHOD: The design was a retrospective case review using
      adult and pediatric tools developed to assess prehospital documentation of
      anatomic and physiologic indicators of significant trauma. RESULTS: There were
      400 adult records with Glasgow Coma Score, the most frequently cited (23.5%).
      Fifty-four percent of the adult cases had at least 1 item checked. There were 104
      pediatric cases reviewed, where 49% of the cases had at least 1 indicator
      checked. CONCLUSIONS: The mandated trauma indicators appear to be valid measures
      for use in trauma research.

PMID- 18080579
TI  - Fluid resuscitation therapy for hemorrhagic shock.
AB  - Hemorrhagic shock is a severe life-threatening emergency affecting all organ
      systems of the body by depriving tissue of sufficient oxygen and nutrients by
      decreasing cardiac output. This article is a short review of the different types
      of shock, followed by information specifically referring to hemorrhagic shock.
      The American College of Surgeons categorized shock into 4 classes: (1)
      distributive; (2) obstructive; (3) cardiogenic; and (4) hemorrhagic. Similarly,
      the classes of hemorrhagic shock are grouped by signs and symptoms, amount of
      blood loss, and the type of fluid replacement. This updated review is helpful to
      trauma nurses in understanding the various clinical aspects of shock and the
      current recommendations for fluid resuscitation therapy following hemorrhagic
      shock.

PMID- 18080580
TI  - Ethical decisions in times of disaster: choices healthcare workers must make.
AB  - Healthcare providers are faced with increasing ethical challenges in providing
      care for patients during times of disaster and other public health emergencies.
      The code of ethics for most healthcare professions is somewhat ambiguous when
      addressing the responsibilities of healthcare providers during these times. The
      American Medical Association has created new, stronger language addressing
      physicians' duty to care for patients since the events of September 11, 2001, but
      other professions have not followed suit. Until such time, healthcare providers
      will continue to be faced with making challenging ethical decisions with little
      direction.

PMID- 18080581
TI  - Gender comparison of exposed trauma and posttraumatic stress disorder in a
      community sample of adolescents.
AB  - This study surveys the prevalence of exposed traumatic events and posttraumatic
      stress disorder among the high school students. A total of 735 students were
      selected by stratified cluster sampling. The self-report trauma checklists and
      Mississippi Scale were used. The most common traumatic experiences were
      "witnessing or being in a bad car accident," "getting some really bad news
      unexpectedly," and witnessing violence. The last 2 experiences were more common
      among girls. The rate of the subjects who scored more than the cutoff point in
      the Mississippi Scale was 27.2%. There is an extremely high rate of exposed
      trauma rate, and approximately one third of them have posttraumatic stress
      disorder symptoms.

PMID- 18080582
TI  - Effects of cyclooxygenase inhibitors on bone and cartilage metabolism--a review.
AB  - BACKGROUND: In this era of increeasing use of Nonsteroidal Anti-Inflammatory
      Drugs (NSAIDs) for treatment of painful/inflammatory disorders, it is necessary
      to review the effect of these drugs on bone and cartilage metabolism.
      Inflammation is an essential component of the healing process in bone, and
      cyclooxygenase (cox-1 and cox-2) enzymes play important roles in fracture repair.
      Therefore, there is concern that NSAIDs, which have anti-inflammatory and
      analgesic properties that are mediated by inhibition of cox-1 and cox-2 may delay
      the healing of bone injuries. Also as newer drugs, selective cox-2 inhibitors are
      being developed to avert the gastrointestinal symptoms of the non-specific
      NSAIDs, it is imperative that these substances are studied for any deleterious
      effect on bone and cartilage metabolism. METHODS: Literature on the subject was
      reviewed using manual library search, articles in journals and internet search.
      The search words were: NSAIDs and bone metabolism, cyclooxygenase inhibitors and
      bone metabolism. The search was done using medscape, ortolink and pubmed search
      engines. The search covered a period of 35 years (1970-2005). RESULTS: NSAIDs can
      either reversibly or irreversibly block the cyclooxygenase pathway thereby
      inhibiting prostaglandin synthesis. These cox inhibitors especially the cox-2
      have been found to inhibit the production of prostaglandins which are necessary
      in bone healing. Prostaglandins play a role in both osteoblastogenesis and bone
      resorption, and so, cox inhibitors suppress these functions. CONCLUSION: NSAIDs
      especially the cox-2 inhibitors should be avoided following fractures or implant
      surgery. They should be reserved for other painful inflammatory disorders in
      which bone resorption and formation mediated by prostaglandins are not required.

PMID- 18080583
TI  - Hazards of surgical diathermy.
AB  - BACKGROUND: Surgical diathermy is an invaluable facility widely used in the
      operating theatre. Its application in surgical practice is rapidly expanding.
      However, its use may be accompanied with hazards, which this review is intended
      to highlight. METHODS: Publications from local and international journals were
      reviewed. RESULTS: The role of diathermy in surgical practice has expanded beyond
      imagination in recent years. The patient, surgeon and the theatre staff are
      frequently exposed to hazards such as burns injury, electrocution, hypoxic
      stress, inhalation of diathermy plume, and gene mutation. However, strict
      adherence to preventive measures such as proper connection and handling of
      diathermy machine, avoidance of inflammable theatre gases, the use of suction
      device, theatre scavenging system and diathermy plume extraction system could
      significantly reduce the hazards. CONCLUSION: Continuous exposure to
      electrocautery appliances in surgical practice is associated with potential
      risks. Optimizing health and safety in work place should be an ongoing goal.
      Hence, all methods geared toward the reduction of these risks to health should be
      emphasized.

PMID- 18080584
TI  - Ethics of clinical trials.
AB  - BACKGROUND: Although clinical trials are conducted far more ethically and safer
      now than they were some decades ago, the elimination of gross abuses has tended
      to highlight more subtle ethical problems. Therefore, research in man, especially
      clinical drug trials, must now take into account ethical and legal requirements.
      This review examines the progress of clinical trial ethics, highlights the major
      ethical principles and challenges involved in the conduct of clinical trials, and
      suggests measures to ensure scientifically and ethically sound clinical trials.
      METHOD: An internet search and a perusal of the literature on the history of
      clinical trials, medical ethics and good clinical practice, reveal that apart
      from laying a general principle, the Oath of Hippocrates did not provide a guide
      on the specific ethical problems involved in undertaking research, an important
      arm of advancement in medical knowledge. Hence, to avert continued ethical abuses
      of subjects during clinical research, the current reference guideliNe--the
      Helsinki Declaration of 1964 (revised in 1975), was adopted by the World Medical
      Assembly. It emphasized four major principles: autonomy, nonmaleficience,
      beneficence and justice. In applying these principles, the researcher must obtain
      a written free and well informed consent from patients who should be aware of
      their right to withdraw from trial at any moment. Where possible, a new drug
      should always first be compared to placebo in order to prove its superiority. He
      must ethically monitor and assess risks and benefits of the trial throughout its
      duration and use a fair procedure in selecting research subjects and must respect
      the concept of inviolability of the human person. Ethical challenges confronting
      clinical trials include the appropriateness of the proposed research, obtaining
      free informed consent, use of medications after completion of drug trials, drug
      toxicities and long-term side effects as well as the release and publication of
      research result. CONCLUSION: To improve protection for research subjects and have
      ethically sound clinical trials, there is need to adhere to global standards and
      legislations; establish, strengthen and empower regulatory bodies; develop
      partnership among stakeholders; intensify public enlightenment and train research
      personnel.

PMID- 18080585
TI  - Human capital flight challenges within an equitable health system.
AB  - BACKGROUND: The issue of human capital flight has been discussed at different
      forums with a consensus opinion that it has its merits and demerits to equitable
      health system. Most often one nation becomes a substantial net exporter of
      talent, leaving the provider nation at risk of depleting its natural supply of
      talent. This paper looks into the historical perspective of human capital flight
      or "brain drain", and its burden. It attempts to elucidate the various causes and
      suggested solutions. The paper's objective is to educate colleagues on the
      conceptual and contextual imperatives of the issue. METHOD: Using a convenient
      sample of key informants who were medical colleagues in Nigeria relevant
      information was sourced from these colleagues, documents from the postgraduate
      medical college of Nigeria and the internet on maters relating to human capital
      flight and brain drain. RESULTS: Every year, thousands of qualified doctors, and
      other professionals leave Nigeria tempted by significantly higher wages, brighter
      prospects for employment and education, stability, food security. CONCLUSIONS: It
      appears that the potential exposure to different working conditions, resources
      and professional environments can be of advantage to the country, should Nigeria
      be able to recall these professionals. It also appears that necessary economic
      reforms that make staying at home rewarding, that is--good leadership, and policy
      planning that seriously looks into rural development, among other issues, are
      keys ingredients to reversing the trend in order to ensure a more equitable
      health system.

PMID- 18080586
TI  - Medical quackery in Nigeria; why the silence?
AB  - BACKGROUND: This paper examines the magnitude and scope of medical quackery
      practice in 21st Century Nigeria and wonders why there is so much complacency in
      tackling the problem. It also proffers solutions to the malady. METHODS:
      Definition and brief history of medical quackery both in the developed world and
      Nigeria is given. The scope of the practice in Nigeria is then examined. RESULTS:
      Medical quackery is rampant in Nigeria; Culprits cut across the whole strata of
      medical and health practitioners. The so called alternative/natural health
      practice has particularly assumed great popularity lately and the Federal
      Government seems to turn the other way in spite of their unsubstantiated, largely
      placebo 'Cures'. Homeopathy, in particular, is a medical quackery per excellence
      and should be banned. Law Enforcement Agents, Medical Practice Licensing Board
      and other Health Professions Licensing Boards, Nigeria Medical Association and
      other Health Profession Associations should take this problem seriously.
      Legislations should be made where they have not been made and enforced where they
      have been made and various professional bodies should not hesitate to sanction
      their erring members who deviate from acceptable practice. The government will
      also do well in addressing the key problems of poverty and illiteracy as these
      are twin brothers that promote the practice and acceptance of medical quackery.
      CONCLUSION: Unless concerted efforts are taken by all stake holders, especially
      the government, in tackling the health care problems in Nigeria, the decay in the
      system will continue and medical quackery will continue to thrive.

PMID- 18080587
TI  - Comparative analysis of urethral catheterization versus suprapubic cystostomy in
      management of neurogenic bladder in spinal injured patients.
AB  - BACKGROUND: The objective of this study was, to prospectively and retro
      respectively evaluate urethral catheterization (UC) versus supra-pubic cystostomy
      (SPC) in prevention of urinary tract infection (UTI) in patients with spinal cord
      injury lesion. METHODS: A total of 125 patients with neurogenic bladder and a
      mean age of 30 years had UC (n=80) and SPC (n=40) at the Jos University Teaching
      Hospital (JUTH) between January 1984 and June 2005. RESULTS: Episodes of UTI were
      significantly more; UC 65% versus 14% forS PC (P< O 0 5). Urinary tract infection
      occurred relatively late in the course of admission, in patient who had SPC.
      Patients in SPC group were significantly satisfied with this management option;
      57% versus 8% for UC. Similarly, mortality at 1 year post admission was
      significantly less; 9% versus 36% for UC and death due to UTI related septicaemia
      was 33% versus 18% respectively. CONCLUSION: It was concluded that SPC was a
      better management option since it was associated with a low morbidity, better
      quality of life and a longer life expectancy than UC.

PMID- 18080588
TI  - Predictors of request for antenatal sex determination among pregnant women in
      Osogbo, Nigeria.
AB  - BACKGROUND: Prenatal ultrasonograpghy is a useful diagnostic tool in modern day
      obstetrics. However, its application in prenatal sex determination would continue
      to attract reactions and comments. The objective of the study was to identify
      factors associated with fetal sex determination during ultrasonography, METHODS:
      A descriptive cross-sectional study was carried out among the pregnant women in
      SouthWestern Nigeria, to determine factors associated with willingness to know
      the sex of their unborn child using structured questionnaires. RESULTS: A total
      of 315 responses were obtained. Two hundred and nineteen (69.5%) respondents were
      interested in knowing the sex of their babies during ultrasonograghy. Younger
      mothers(= 29 years), primipara, those who had preference for a particular sex,
      those who planned to have more children based on desired sex, those who had
      problems detected in the index pregnancy and women who planned the index
      pregnancy were more willing to know the sex of their unborn child. Adjusting for
      other factors, pregnancies that were planned, determination to have more babies
      and house re-arrangement based on fetal sex of the index pregnancy were found to
      be significantly associated with desire to have prenatal sex determination.
      CONCLUSION: The study has demonstrated the factors that influence the request for
      prenatal sex determination among the pregnant women in Southwestern Nigeria and
      the effects of western influence.

PMID- 18080589
TI  - Seroprevalence of hepatitis B surface antigenaemia in children in a tertiary
      health institution in the Niger Delta of Nigeria.
AB  - BACKGROUND: There is paucity of data on the seroprevalence of HBV infection in
      children living in urban areas of the Niger Delta of Nigeria. The aim of this
      study is to determine the seroprevalence of hepatitis B surface antigenaemia
      among children presenting to the University of Port Harcourt Teaching Hospital
      (UPTH), to determine the trend in the seroprevalence of HBsAg over a five-year
      period and to correlate serological findings to clinical features. METHODS: Serum
      samples from 251 consecutively recruited children in UPTH aged =16 years were
      tested for Hepatitis B surface antigen using Clinotech HBsAg kits and confirmed
      using the Trinity Biotec enzyme linked immunosorbent assay based HBsAg kits.
      Medical records of the children were also obtained. RESULTS: The overall
      prevalence of HBsAg among children tested was 12.4%. HBsAg prevalence was highest
      in the 11-15 years age group (24.5%) and the lowest in the 6-10 years age group
      (11.0%). There was a statistically significant difference in the prevalence of HB
      V positivity based on age groups (?2, = 8.47, p = 0.014). Prevalence rate was
      relatively higher among males (13.7%) compared to females (10.7%). There is a
      statistically significant trend in the decline of HBsAg prevalence 1999 to 2004
      (?2, for trend = 11.38, p = 0.001). The predominant symptoms among children
      positive for HBsAg were hepatosplenomegaly (75%) and jaundice (64.5%).
      CONCLUSION: This study indicates a high prevalence of HBsAg among children
      presenting to a tertiary health facility in Port Harcourt.

PMID- 18080590
TI  - Changing pattern for extremity amputations in University of Maiduguri Teaching
      Hospital, Nigeria.
AB  - BACKGROUND: Trauma has been the major indication for limb amputation in almost
      all studies emanating from the different parts of Nigeria, except in Maiduguri.
      Earlier studies from this part of the country recorded malignancy as the leading
      indication for amputation. There is need to review the current pattern of causes.
      The aim of this study is to ascertain the current indications for amputation in
      the University of Maiduguri Teaching Hospital and compare the findings with
      similar studies conducted in this centre about 15 years ago with a view to
      highlighting the changes in the pattern of causes. This would enable meaningful
      preventive measures to be proffered. METHODS: Case notes of all patients that
      underwent amputation surgery at the University of Maiduguri Teaching Hospital
      between January 2000 and December 2004 were retrieved and retrospectively
      studied. Data collected from the folders include demographic indices, indication
      for amputation, level and laterality of amputation, follow up visits and use of
      prosthesis. RESULTS: Forty-five patients' case notes with 49 amputations were
      analyzed. The male to female ratio was 3.5:1. The peak age incidence was in the
      4th and 5th decade with 18 patients (40%). Trauma accounted for the highest
      indication with 21 amputations (42.8%) while malignancy was responsible for only
      9 (18.4%). There were more lower extremity amputations, 35 (71.4%), as compared
      to the upper extremity, 14 (28.6%). Below knee amputation was the commonest
      amputation carried out constituting 22 (62.8%) of the 35 lower limb amputations.
      CONCLUSION: Trauma, especially following from road traffic accidents was the
      major cause of limb loss in this part of Nigeria. Concerted efforts at enforcing
      the already existing traffic laws and regulations would go a long way in reducing
      the number and severity of cases of road traffic injuries that would require
      amputation.

PMID- 18080591
TI  - Fetal outcome following umbilical cord prolapse in Ahmadu Bello University
      Teaching Hospital, Kaduna (ABUTHK), northern Nigeria.
AB  - BACKGROUND: Umbilical cord is a clinical condition that calls for emergency
      decision making and action especially with a live and mature fetus. The objective
      of this study is to determine, fetal outcome and how various factors influence
      it. METHODS: This is a 12 1/2 year retrospective study of all 34 fetuses who
      suffered from cord prolapse at Ahmadu Bello University Teaching Hospital.
      RESULTS: There were 34 cases of cord prolapse, 23 perinatal deaths and a
      perinatal mortality rate of 67.64%. About 55% of babies of registered women died,
      while about 92% of the unregistered died. Eleven babies of the 22 women admitted
      with cervical dilatations of 7 cm and less, died and all the babies of women with
      cervical dilatations of 8 cm and above died. All 19 babies delivered vaginally
      and 3 of the 14 delivered abdominally, died. About eighty eight percent of the
      low-birth weight, and 37.5% of normal size babies died. Seventeen (51.5%) of the
      33 babies delivered, had Apgar score 0. All babies with Apgar scores 1-4 died,
      40% with Apgar scores 5-7 and 16.7% with Apgar scores 8-10 died. Maternal age,
      parity, ethnicity, gestational age, presentation and sex of the fetus did not
      influence outcome.

PMID- 18080592
TI  - Sexual behaviour and predictors of condom use among students of a Nigerian
      tertiary institution.
AB  - BACKGROUND: Increasing sexual networking among university students exposes them
      to the risk of sexually transmitted infections (STIs) including HIV/AIDS. Despite
      this, the level of condom use and sexual abstinence is low. OBJECTIVE: The
      objective of the study was to describe sexual behavior and identify predictors of
      condom use among students in a Nigerian university. METHODS: A cross sectional
      survey was conducted using self-administered questionnaires among 404 students of
      the Federal university of Technology, Minna in northern Nigeria. FINDINGS: A
      total of 328 (81.2%) questionnaires were completed and returned. There were 230
      male and 98 female respondents giving a sex ratio of 1:2.3. The respondent's ages
      ranged from 16 to 38 years with an overall mean of 23.53.51 years. A
      significantly higher proportion of males 184 (80.0%) reported being sexually
      experienced compared to 64 (65.0%) females (chi2 = 8.05 P < 0.05). The mean age
      of first sexual experience was also significantly higher among male students
      [18.92.1 years] compared to female students [16.41.7 years] (t = 11.36, P <
      0.01). Similarly, a significantly higher proportion (56.2%) of sexually active
      males had multiple partners compared to females (38.1%) (chi2 = 11.9, P = 0.001).
      In addition, the mean number of lifetime sexual partners was significantly higher
      (5.3) for males compared to females (2.6) [t = 12.0, P < 0.001]. Condom was
      consistently used by 38.3% (n=95) of sexually active students in both genders. A
      higher proportion (44.6%) (n=82) of male students reported regular use of condoms
      compared to (20.3%) (n=13) of (partners of) sexually active female students (chi2
      = 11.8 P = 0.001). Significant predictors of regular condom use include (male)
      gender, (higher) level of study and (single) marital status. CONCLUSION: Most
      students were sexually active and many practiced unsafe sex. This indicates the
      need for youth friendly reproductive health programmes targeting these students.

PMID- 18080593
TI  - The trend of HIV infection in Kano, Nigeria--a seven-year study of adult
      attendees of Aminu Kano Teaching Hospital.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is a huge concern with
      increasing epidemic proportions The consequences are devastating in developing
      countries particularly in large areas of southeast Asia and sub Saharan Africa
      including decrease in life-expectancy, huge loss of manpower and a heavy economic
      and social burden. Sub-Saharan Africa has been hit harder by HIV/AIDS pandemic
      than any other region of the world At the end of 2006, the Joint United Nations
      Programme on HIV/AIDS (UNAIDS) estimated that, globally 39.5 million people were
      living with HIV/AIDS, out of which 24.7 million were in sub-Saharan Africa. To
      determine the annual trend of HIV infection in Kano as well as the seroprevalence
      rates over the years. METHOD: This retrospective study includes all adults that
      are 15years and above, who are also AKTH attendees and. patients referred from
      other hospitals in Kano, who, based on clinical suspicion, were sent to the
      serology laboratory of the hospital for HIV screening and confirmation between
      January, 1997 and December, 2003. It however, excludes all pediatrics, antenatal
      care clinic attendees and all blood donors screened for HIV antibodies within the
      period. These have been collated under various risk groups elsewhere. RESULTS: Of
      9241 subjects tested, 3217 (34.8%) were confirmed seropositive for HIV antibodies
      consisting of 1908 (36.7%) and 1441 (35.7%) males and females respectively
      Analysis of results on yearly basis shows prevalence rates of 37.1% in 1997, 40%
      in 1998 and 47.9% in 1999. However, the HIV seroprevalence rates declined to
      22.6% among these subjects in 2000 before rising to the peak (48.8%) in 2002 from
      30% seroprevalence of the previous year, 2001. The prevalence rate for 2003 was
      32.1%. effective control strategies aimed at curbing the spread of HIV infection.

PMID- 18080594
TI  - Prevalence and magnitude of trachoma in a local government area of Sokoto State,
      north western Nigeria.
AB  - INTRODUCTION: In order to have baseline data for monitoring and evaluation of
      trachoma control activities in Sabon Birni LGA of Sokoto state Nigeria, a
      population based trachoma survey was conducted. The survey was designed to
      determine the prevalence of active trachoma and trichiasis as well as assess the
      prevalence of major risk factors for trachoma in the study area. METHOD: The
      survey was a population based cross sectional survey of persons of all ages in
      the study area. A minimum sample size of 2760 was determined and the study
      population was selected by two stage cluster random sampling technique. In the
      first selection stage 34 communities were randomly selected by probability
      proportional to size, while for the second sampling stage 90 persons of all ages
      were randomly chosen in each selected cluster. All chosen persons were assessed
      for trachoma using WHO trachoma simplified grading system and their households
      were assessed for trachoma environmental risk factors. RESULTS: The prevalence of
      blindness in the study population was 2.0% (95% CI 1.4%-2.6%) with trachoma
      responsible for l3.8%. The prevalence of active trachoma amongst children (1-9
      years) was 37% (CI 34.3%-39.8%), while trichiasis amongst adults was 2.3% (95% CI
      1.9%-2.7%). Over sixty percent of households had no functional latrine, while 81%
      of households had refuse and animal dung littered within their compounds. Sixty
      percent of children had 'unclean faces' and over 85% of households had access to
      water within their villages. CONCLUSIONS: Trachoma of public health concern still
      exists in some districts of northern Nigeria with significant environmental risk
      factors.

PMID- 18080595
TI  - The incidence and outcome of bilirubin encephalopathy in Nigeria: a bi-centre
      study.
AB  - OBJECTIVE: To determine the current trends in the incidence and outcome of
      bilirubin encephalopathy among Nigerian babies. METHODS: A review of the hospital
      records of babies managed for bilirubin encephalopathy at the Wesley Guild
      Hospital (WGH), Ilesa and Olabisi Onabanjo University Teaching Hospital (OOUTH),
      Sagamu, both in southwest Nigeria between 2001 and 2005 was carried out. The age,
      sex, weight, body temperature on admission, place of delivery and outcome of
      hospitalization were studied. The fatal cases and the survivors were compared for
      risk factors for mortality. RESULTS: Fifty eight (3.4%) and 57 (2.3%) babies had
      bilirubin encephalopathy out of 1706 and 2492 total neonatal admissions at OOUTH
      and WGH respectively. Of these 115 babies, 3 (2.6%), 84 (73.0%) and 28 (24.3%)
      were aged <3 days, 3-6 days and 7 days or more. Sixty eight (59.1%) babies were
      delivered in orthodox health facilities. Aside clinically suspected cases of G6PD
      deficiency, ABO incompatibility and septicaemia were commonly associated with
      bilirubin encephalopathy, Forty four (38.3%), 36 (31.3%) and 35 (30.4%) had
      Unconjugated bilirubin of <340 micromol/L, 341-425 micromol/L and >425 micromol/L
      respectively Sixty eight (59.1%) were discharged, 42 (36.5%) died while 5 (4.7%)
      were discharged against medical advice. Prematurity, low birth weight, severe
      anaemia and inability to do Exchange Blood Transfusion were significant risk
      factors for mortality among babies with bilirubin encephalopathy. Cerebral palsy,
      seizure disorders and deafness were the leading neurological sequelae (86.4%,
      40.9% and 36.4% respectively) among the 22 survivors who were followed up.
      CONCLUSION: Bilirubin encephalopathy remains a common clinical finding in Nigeria
      and the associated mortalities and neurological sequelae are significant.

PMID- 18080596
TI  - The effect of in-vivo intravenous administration of sodium meglumine diatrizoate
      on some haematological parameters.
AB  - BACKGROUND: To investigate the in-vivo effects of intravenous administration of
      sodium meglumine diatrizoate on some haematological parameters in a Nigerian
      population. METHODS: Blood samples were collected before and one hour after
      intravenous injection of sodium-meglumine diatrizoate from 50 subjects undergoing
      intravenous urography examinations who had no history of and laboratory confirmed
      diseases that may affect haematological parameters. Standard laboratory methods
      were used to assay the haemoglobin concentration (Hb), packed cell volume (PCV),
      total white blood cell (WBC) count and differentials and blood film for any
      morphological changes in the red blood cells (RBC). Comparisons were made between
      the mean values of these haematological parameters before and one hour post
      injection using paired t-test for any statistically significant differences.
      RESULTS: There were statistically significant reductions in the mean values of Hb
      concentration and the neutrophil count one hour post injection compared with
      their pretest values (p < 0.05). The lymphocytes were also significantly
      increased post injection compared to the pretest values whereas 70% of the
      erythrocytes were morphologically altered from their approximately 100%
      normocytic shape at pre-test. CONCLUSION: Intravenous administration of sodium
      meglumine diatrizoate causes in-vivo reduction in Hb concentration and neutrophil
      count in humans as well as poikilocytosis of the erythrocytes. Some of these
      effects have the potential of triggering or exacerbating crisis in a sickle cell
      anaemia subject which is endemic in our locality. Caution should therefore be
      exercised in the choice and administration of radiological contrast agents to
      sickle cell subjects. Preparations that are iso-osmolar with plasma and have less
      probability in precipitating crises should be preferred instead.

PMID- 18080597
TI  - Comparison of emergency caesarean section to misoprostol induction for the
      delivery of antepartum eclamptic patients: a pilot study.
AB  - BACKGROUND: Eclampsia has now emerged as one of the commonest cause of maternal
      mortality in Nigeria. There is need for research on best modality for delivery of
      eclamptics. METHODOLOGY: The pilot study was conducted on 50 eclamptic patients
      at the Federal Medical Centre, Azare. The patients were randomized for delivery
      either by caesarean section (CS) or induction of labour. The fetomaternal outcome
      of the two groups was compared. RESULTS: 25 of the patients had CS and 25 had
      induction of labour with misoprostol. The mean decision delivery interval was 4.1
      hours and 13.08 hours for the CS and misoprostol groups respectively. Misoprostol
      failure was recorded in 4 (16%) patients and they were subsequently delivered by
      CS. The duration of admission was longer in the CS group (mean of 10.1 days)
      compared to the misoprostol group (mean of 6.08 days). There were more maternal
      complications and admissions of babies into the SCBU in the CS group. Maternal
      mortality in the two groups was similar (2% each). CONCLUSION: Misoprostol is
      cheap, available and safe for delivery of antepartum eclamptics. In the event of
      delay at caesarean section for antepartum eclamptics patients, misoprostol
      induction should be started. A multicenter study is called for.

PMID- 18080598
TI  - Neural tube defects in a university teaching hospital in southern Nigeria: trends
      and outcome.
AB  - BACKGROUND: There has been some increase in the proportion of Neural Tube Defects
      (NTD) admitted in the University of Port Harcourt Teaching Hospital recently.
      Fora largely preventable birth defect, this increase is both unnecessary and
      unacceptable. This study was undertaken to describe the admission patterns and
      outcome of neural tube defects in University of Port Harcourt Teaching Hospital.
      METHODS: A retrospective study of babies with neural tube defects who were
      admitted into Special Care Baby Unit (SCBU) of the University of Port Harcourt
      Teaching Hospital from 1st May 2002 to 30th April 2005 was carried out. Their
      case notes were retrieved and information on the sex, maternal drugs during
      pregnancy, type of defect and associated malformations, prenatal diagnosis,
      management and outcome were obtained. The admission rate and the incidence were
      then calculated. RESULTS: There were 2891 total admissions (1691 males and 1200
      females) during the study period of which 37 (1.3%) were neonates with NTD. Of
      those with NTD, 25 were males and 12 female giving a male to female ratio of 2:1
      (statistically not significant p = 0.242.) The total hospital delivery at the
      study period was 7,388 of which 7 had NTD giving an incidence of 0.95/1000
      deliveries. The commonest type of NTD was myelomeningocoele in 31 (83.8%), and
      the commonest site was the thoracolumbar region (93.5%). Frontal encephalocoele
      was seen in 6 (16.2%). All the babies with myelomeningocoele presented with
      flaccid paraparesis and were incontinent of both urine and faeces. Seventeen of
      the babies had only spina bifida while 14 had additional defects including
      talipes equinovarus (8), hydrocephalus (2), frontal encephalocoele (1), and
      multiple malformations (3). Ten babies (27%) died, three of them after surgery.
      All the mothers received folic acid from the second trimester of pregnancy, but
      none did before pregnancy. CONCLUSION: The Incidence of NTD is on the increase in
      our environment. There is need to formulate/implement the policy of
      preconceptional folic acid therapy for all woman of childbearing age as a
      preventive measure

PMID- 18080599
TI  - Elective caesarean section at the Federal Medical Centre Makurdi, north central
      Nigeria.
AB  - BACKGROUND: Elective caesarean section is associated with less risk of adverse
      events compared to emergency caesarean section. Paradoxically, emergency
      caesarean deliveries continue to form the bulk of caesarean deliveries in our
      facility. The aim of this study is to determine the caesarean section rate,
      ascertain the trend of elective caesarean section, indications for elective
      caesarean section and elective caesarean mortality. METHODS: A retrospective
      analysis of the clinical records of all patients that had caesarean section
      between January 2004 and December 2006 at the Federal Medical Centre Makurdi was
      conducted. RESULTS: There were 4011 deliveries with 420 caesarean sections during
      the review period giving a caesarean section rate of 10.5%. The elective
      caesarean sections accounted for 69(16.4%) while emergency caesarean sections
      accounted for 351(83.6%) of all caesarean sections. The rate of elective
      caesarean section increased from 10.3% in 2004 to 22.8% in 2006 of all caesarean
      sections. Two or more previous caesarean sections were the commonest indication
      for elective caesarean section accounting for 23.2% of cases, followed by HIV
      infection in pregnancy accounting for 21.7% of cases. No maternal death occurred
      with elective caesarean section. CONCLUSION: There is a rising trend of elective
      caesarean section presently accounting for 1 out of every 6 caesarean sections in
      the centre. The commonest indication for elective caesarean section was two or
      more caesarean sections, followed by retroviral disease in pregnancy. Elective
      caesarean section remains safer than emergency caesarean section in our facility.

PMID- 18080600
TI  - Burden of domestic violence amongst infertile women attending infertility clinics
      in Nigeria.
AB  - BACKGROUND: Infertility affects about 20% or more of the population. Infertility
      can lead to domestic violence and any woman who experiences domestic violence
      because of infertility, has a double jeopardy. METHODS: This was a cross
      sectional study involving 233 infertile women attending infertility clinics in 3
      hospitals in Nigeria overa period of 12 months. RESULTS: Ninety seven (41.6%) of
      the women had experienced domestic violence because of their infertility state.
      The forms of domestic violence experienced were psychological torture 50 (51.5%),
      verbal abuse 38 (39.2%), ridicule 27 (27.8%), physical abuse 17 (17.5%) and
      deprivation 6 (6.2%). The main culprits were the husband 47 (48.5%) and female in
      laws 31 (32%). Yoruba women were more likely to experience domestic violence than
      other tribes, although this difference did not reach statistical significance ( p
      > 0.05.) Educational level, parity, type of marriage and duration of infertility
      were not statistically significant (p > 0.05). CONCLUSION: In this setting,
      infertile women are prone to domestic violence. Prompt evaluation, counselling of
      the couple, as well as early treatment and prevention of infertility is necessary
      to avoid the problem and domestic violence. This should form part of efforts to
      meet the millennium development goals.

PMID- 18080601
TI  - Osteoclastoma in an infant.
AB  - BACKGROUND: Conventionally, osteoclastoma is a benign but locally aggressive bone
      tumour with a tendency for local recurrence and rarely distant metastasis,
      diagnosed mainly in young adults, 15-40 years of age. Diagnosis before skeletal
      maturity is circumspect. We report a case of giant cell tumour of the clavicle
      (uncommon site) in a 2% year old girl that was first noticed at 6 months of age.
      METHOD: The case files of the patient as well as relevant literature were
      reviewed. RESULTS: A 2%-year-old girl presented with a 2-year history of right
      clavicularswelling first noticed at 6 months of age. The mass was initially
      painless and very slow growing involving the medial third of the clavicle. It
      rapidly increased in size to involve the entire clavicle with associated pain
      following manipulation by a traditional bone setter about 6 months after onset.
      She had incisional biopsy; the histological report of which was osteoclastoma.
      She then had excision of the mass with the involved clavicle uneventfully. She is
      being followed up for recurrence. CONCLUSION: Osteoclastoma can develop in early
      childhood far before skeletal maturity, may be congenital in manifestation and
      can affect anybone in the body.

PMID- 18080602
TI  - Psychological effects of speech disorders in an adult patient with untreated
      cleft palate.
AB  - BACKGROUND: Cleft palate of the primary or secondary type, is accompanied with
      various devastating physical and psychological effects. The purpose of this case
      study was to highlight the psychosocial problems the patients with these defects
      encounter both at the initial and later stages oftheirlives. METHOD: The case
      study focused on the history and clinical examination of a 25-year-old, single,
      female patient who presented with hypernasality and misarticulation of speech
      secondary to an incomplete cleft of the secondary palate which was not treated.
      RESULTS: The patient was found to break down with tears in the process of
      discussion about her social life; she disclosed having problems with interacting
      with the society and especially with her male friends. Examination revealed a 5
      centimeter (cm) long and 2 cm wide central defect involving the soft palate/uvula
      and causing a communication between the oral cavity/oropharnyx and nasal
      cavity/nasopharnyx. The patient was counseled and asked to come for surgery.
      However she has not come back since the day she came to our clinic. CONCLUSION:
      Speech defects in longstanding untreated clefts are not easily correctable and
      these have associated life-long impact on the quality of life of the patients,
      therefore, because some parents are afraid of surgical operations and may not
      want to subject the children to this treatment, this study will enlighten the
      clinicians to inform and emphasize to the parents/relations about these speech
      defects and psychological implications that will result if the children are not
      treated and even at the appropriate time.

PMID- 18080604
TI  - The quest for safer surgery.

PMID- 18080603
TI  - Dupuytren's contracture in a patient with type 2 diabetes mellitus--a case
      report.
AB  - BACKGROUND: Dupuytren's contracture is one of the manifestations of the hand
      syndrome in diabetes mellitus (DM). Its occurrence in diabetes mellitus is not
      commonly reported in this environment. This report aims to highlight the
      occurrence of Dupuytren's contracture as a rare manifestation of diabetic hand
      syndrome in a patient with type 2 DM. METHOD: The case note of a patient with
      type 2 DM who developed Dupuytren's contracture in both hands and the available
      literature on the subject were reviewed. RESULT: A 62-year-old Nigerian male
      Islamic Cleric with type 2 DM for sixteen years on follow-up at the Diabetes
      clinic of the Jos University Teaching Hospital (JUTH), Jos, developed flexion
      deformity involving both palms. His symptoms had progressed gradually over the
      preceding nine months before presentation. Physical examination revealed
      bilateral Dupuytren's contracture of the palms with hyperkeratosis and flexion
      deformities of the fingers. He was admitted to the surgical ward of JUTH and had
      surgery in the right hand. He is to have surgery in the left hand on a later
      date. CONCLUSION: Dupuytren's contracture is a rare presentation of diabetic hand
      syndrome. A careful hand examination by physicians in all DM patients for early
      diagnosis and treatment is recommended.

PMID- 18080605
TI  - Mortality and morbidity associated with late diagnosis of anorectal malformations
      in children.
AB  - AIM: The aim of this study was to highlight the timing of diagnosis of anorectal
      malformations and the morbidity and mortality associated with any delay. METHODS:
      We retrospectively reviewed all patients with anorectal malformations presenting
      to the Children's Hospital, Leicester between 1998-2005. Patient demographics
      included age at diagnosis, presenting complaint, type of anorectal malformation
      and sex. Associated malformations were carefully recorded as well as morbidity
      and mortality occurring as a consequence of the delay in diagnosis. RESULTS: Out
      of a total of 52 patients, 28 (53%) had delay in diagnosis of the malformation.
      This delay was associated with significant morbidity in 19% and sadly included
      two deaths (4%), both being directly related to the missed diagnosis. CONCLUSION:
      Despite the established, routine, systematic pre-discharge examination in all
      neonates, a significant proportion of anorectal malformations are not diagnosed
      at this time. This delay is the cause of significant morbidity and mortality.
      Simple perineal examination will clearly identify the existence of all anorectal
      malformations and therefore such morbidity and mortality is totally avoidable.

PMID- 18080606
TI  - Intravesical botulinum toxin type A in chronic interstitial cystitis: results of
      a pilot study.
AB  - AIM: To assess the efficacy of intravesical botulinum toxin type A (BTX-A) in
      interstitial cystitis (IC). METHODS: Eleven patients with IC were injected with
      BTX-A. Primary outcome measures were: Bristol Female Lower Urinary Tract Symptom
      Score, Kings Health Questionnaire and 24-hour frequency-volume chart. They had
      urodynamics done before and six weeks after injection. Detrusor contractility was
      assessed using the modified PIP1 (projected isovolumetric detrusor pressure).

PMID- 18080607
TI  - The treatment of non-union of the clavicle with the AO mini external fixator.
AB  - Osteosynthesis of non-union of fractures of the clavicle were achieved using bone
      graft and the AO mini external fixator. The technique was used in nine patients,
      and no neurovascular or pleural complications occurred. The average time before
      the patient was considered for this method was 11 months. The external fixator
      was removed at an average of eight weeks, with solid union in all cases. The
      outcome was excellent and all patients returned to pre-injury level of normal
      activity. This method provides safe and relatively simple treatment for this
      difficult non-union.

PMID- 18080608
TI  - Incentive spirometry decreases respiratory complications following major
      abdominal surgery.
AB  - Pulmonary complications are the leading cause of morbidity and mortality
      following major abdominal surgery. Chest physiotherapy aims to decrease the
      likelihood of these complications and hasten recovery. Exercises aimed at
      maximising inspiratory effort are the most beneficial for the patients. The
      incentive spirometer is a handheld device that patients use to achieve effective
      inspiration. In a nonrandomised pilot study of 263 patients we have found that
      the addition of the incentive spirometer, as part of an intensive post-operative
      physiotherapy programme, decreased the occurrence of pulmonary complications (6
      vs 17%, p = 0.01) and length of stay on the surgical high dependency unit (3.1 vs
      4 days p = 0.03). The two groups were comparable when age, sex, smoking history,
      the need for emergency surgery and post-operative analgesia were compared.

PMID- 18080609
TI  - Psychosocial factors and quality of life in colorectal cancer.
AB  - INTRODUCTION: Colorectal cancer (CRC) is one of the most common cancers in the
      UK. Quality of life (QoL) is increasingly being recognised as an important
      endpoint in the management of CRC. METHODS: Publications describing QoL in CRC
      were identified using Medline (PubMed) and PsychINFO. Reference lists of these
      articles were used to identify other relevant publications. RESULTS: Seventy-two
      publications described QoL changes in CRC. These were grouped into three
      categories: studies of psychological and psychiatric morbidity in CRC patients,
      QoL and survival in CRC and effects of psychological intervention on QoL and
      survival. CONCLUSION: Assessment of QoL is becoming increasingly important but is
      not routinely performed in CRC. Standard, validated and reliable questionnaires
      to evaluate the impact of cancer and its treatment in patients are available.
      There is an increasing need to establish comprehensive biopsychosocial databases
      to evaluate the relationship between QoL and survival in CRC.

PMID- 18080610
TI  - Surgery for ulcerative colitis.
AB  - Ulcerative colitis is an inflammatory condition of unknown aetiology affecting
      all or part of the rectum and colon. The mainstay of treatment is medical but
      there are specific indications for surgical intervention. This article reviews
      the evolution of surgical management and in particular compares outcome from
      proctocolectomy and pouch surgery. A number of factors determining choice of
      procedure are examined, including elective or emergency presentation, patient
      selection, technical issues, morbidity and quality of life. Emphasis is made
      regarding a full explanation of these factors so that the patient is fully
      involved in the final decision regarding choice of procedure.

PMID- 18080611
TI  - A stepped care approach to reduction of anterior shoulder dislocation in the
      prone position.
AB  - There are various methods of reducing anterior shoulder dislocations. The
      traditionally used methods like Kocher's and Hippocratic are associated with
      procedural complications and frequently require sedation/muscle relaxants which
      have their own complications and are associated with longer stay and monitoring
      requirement in the emergency department. We describe a stepped care approach to
      shoulder dislocation reduction in the prone position involving four steps and two
      new manipulation methods taking into consideration the pathological deforming
      forces in a dislocated shoulder and addressing them in a stepwise fashion. This
      method does not require sedation/muscle relaxants in the majority of cases, is
      easy to learn, relatively painless, associated with shorter stay in the emergency
      department and has fewer complications.

PMID- 18080612
TI  - Perforation of a retrocaecal appendix presenting clinically as a right lumbar
      abscess.
AB  - Presentations of acute appendicitis represent an ongoing challenge to surgeons.
      This case of retrocaecal perforated appendicitis presented clinically as a right
      lumbar abscess, with the concomitant new diagnosis of type 2 diabetes mellitus in
      a 66-year-old male. This case emphasises the importance of an abdominal CT scan
      in any patient presenting with unusual sepsis near the abdomen.

PMID- 18080613
TI  - Re: Modernising Medical Careers in surgery: can we adopt elements of the South
      African model?

PMID- 18080614
TI  - Re: Axial fixation of testes for prevention of recurrent testicular torsion.
      Surgeon 2006; 3(1): 20-21.

PMID- 18080615
TI  - Study supports activity of gemcitabine in treatment of early-stage breast cancer.

PMID- 18080616
TI  - Use of gene-expression profiling to recommend adjuvant chemotherapy for breast
      cancer.
AB  - One of the primary challenges in the treatment of patients with early-stage
      breast cancer is determining which patients will benefit from adjuvant
      chemotherapy. Traditionally, treatment decisions have been made based on a
      combination of tumor characteristics and patient and physician perspectives
      regarding risks and benefits. Recent technologic advances, including the
      development of gene-expression arrays, have led to the identification of
      molecular signatures that provide prognostic information in addition to the basic
      clinicopathologic features of individual tumors. While these new methods allow
      for more refined determination of prognosis for an individual patient, few data
      are available to support use of these new technologies in the clinic for
      treatment decision-making. At present, data from a single retrospective study are
      available to support the use of one assay, the 21-gene recurrence score, for
      decision-making regarding adjuvant chemotherapy. Large, multinational clinical
      trials are currently ongoing to evaluate the use of two of the multiparameter
      assays, although it will be many years before oncologists can apply the results
      of these trials in the clinic.

PMID- 18080617
TI  - Chemotherapeutic Strategies for advanced breast cancer.
AB  - Disease-free and overall survival have improved significantly for women diagnosed
      with early-stage breast cancer. At the same time, systemic therapy has only
      slightly enhanced long-term outcomes in advanced breast cancer, a disease that
      remains largely incurable. Several single-agent and combination chemotherapy
      approaches are available to women with hormone-insensitive advanced disease that
      may improve overall survival and progression-free survival, minimize symptoms and
      complications related to the disease, and improve overall quality of life. In
      addition, new cytotoxic and targeted agents have been recently introduced into
      practice and have improved both survival outcomes and quality of life. In this
      review, we will provide an update on commonly used chemotherapy-based regimens
      for the treatment of metastatic breast cancer, with a focus on tailoring therapy
      to different subtypes of the disease.

PMID- 18080618
TI  - Molecular targets on blood vessels for cancer therapies in clinical trials.
AB  - This review covers progress to date in the identification of molecular targets on
      blood vessels in cancers, as well as agents that act on those targets, with
      emphasis on those currently in clinical trials. Current vascular-targeting
      therapies comprise two general types--antiangiogenic therapy and antivascular
      therapy. Advances in antiangiogenic therapies, particularly inhibitors of
      vascular endothelial growth factors and their receptors, have clarified the
      capacity of these inhibitors to change tumor-associated vessel structure to a
      more normal state, thereby improving the ability of chemotherapeutics to access
      the tumors. The responses of other antiangiogenesis target molecules in humans
      are more complicated; for example, alphanubeta3 integrins are known to stimulate
      as well as inhibit angiogenesis, and cleavage of various extracellular
      proteins/proteoglycans by matrix metalloproteinases produces potent regulators of
      the angiogenic process. Antivascular therapies disrupt established blood vessels
      in solid tumors and often involve the use of ligand-based or small-molecule
      agents. Ligand-based agents, irrespective of the antiangiogenic capacity of the
      ligand, target antivascular effectors to molecules expressed specifically on
      blood vessels, such as aminopeptidase N, fibronectin extra-domain B, and prostate
      specific membrane antigen. Small-molecule antivascular agents, which are not
      targeted to molecules on blood vessels, rely on physical differences between the
      vasculatures in tumors and those in normal tissues.

PMID- 18080619
TI  - Management of Barrett's esophagus.
AB  - Barrett's esophagus represents replacement of normal distal esophageal squamous
      epithelium with specialized columnar epithelium containing goblet cells.
      Typically arising in the setting of chronic gastroesophageal reflux disease, the
      presence of Barrett's esophagus carries a 50- to 100-fold increased risk of
      developing esophageal cancer. Risk factors include male sex, smoking history,
      obesity, Caucasian ethnicity, age > 50 and > 5-year history of reflux symptoms.
      Aggressive medical or surgical antireflux therapy may ameliorate symptoms, but
      have not yet been proven to affect the risk of developing esophageal
      adenocarcinoma in randomized trials. Although dysplasia is an imperfect biomarker
      for the development of subsequent malignancy, random sampling of esophageal
      tissue for dysplasia remains the clinical standard. There have been no studies to
      establish that endoscopic screening/surveillance programs decrease the rates of
      death from cancer. Fit patients with Barrett's esophagus and high-grade dysplasia
      should undergo esophagectomy to prevent the risk of developing esophageal
      adenocarcinoma. For non-operative candidates, endoscopic ablative approaches may
      represent a reasonable therapeutic alternative.

PMID- 18080620
TI  - 'SiCKO'.

PMID- 18080621
TI  - The impact of nurse staffing on hospital costs and patient length of stay: a
      systematic review.
AB  - Research examining the relationships between nurse staffing, hospital costs, and
      length of stay is varied using a range of methods and definitions. This lack of
      coherence in definitions and measurement tools for cost and length of stay makes
      it difficult to conclude with certainty the results of nurse staffing on hospital
      cost and length of stay. However, the evidence reflected that significant
      reductions in cost and length of stay may be possible with higher ratios of
      nursing personnel in hospital settings. Sufficient numbers of RNs may prevent
      patient adverse events that cause patients to stay longer than necessary. Patient
      costs were also reduced with greater RN staffing as RNs have higher knowledge and
      skill levels to provide more effective nursing care as well as reduce patient
      resource consumption. Hospital administrators are encouraged to use higher ratios
      of RNs to non-licensed personnel to achieve their objectives of quality patient
      outcomes and cost containment.

PMID- 18080622
TI  - What role can nurse leaders play in reducing the incidence of pressure sores?
AB  - Pressure sores have plagued the nursing profession for many years as a major
      health care problem in terms of a patient's suffering and financial cost.
      Pressure sores are increasingly common in hospitalized patients in the United
      States with a 63% increase from 1993 to 2003. The nurse leader is accountable for
      the occurrence of pressure sores, a nurse-sensitive indicator, by a scorecard
      which is benchmarked against other facilities. The nurse leader must take a
      systematic approach in the prevention of pressure sores, with the strategy being
      consistent and motivating to the staff in order to improve patient outcome. The
      chief nursing officer, the unit manager, and the bedside nurse must all
      collaborate to prevent tissue injury in patients at risk for developing pressure
      sores and to promote wound healing in patients with existing breakdown.

PMID- 18080623
TI  - Validating HRSA's nurse supply and demand models: a state-level perspective.
AB  - In addition to federal initiatives, solutions to the nursing shortage must also
      be devised at the state level. Understanding the timing and severity of the
      nursing shortage in a particular state is paramount to devising appropriate
      solutions In 2005, the Health Resources and Services Administration released new
      versions of the Nurse Supply Model and Nurse Demand Model designed to project the
      supply of RNs and demand for RNs, LPNs, and nurse aides in the United States
      through the year 2020. The process used by two state-level analysts to project
      nurse supply and demand in North Carolina using the HRSA models is described. The
      authors conclude that the models work well for state-level forecasting but that
      users should carefully assess the default data provided with the model against
      independent data sources specific to their states.

PMID- 18080625
TI  - Politics, economics, and nursing shortages: a critical look at United States
      government policies.
AB  - The economic concept that the independent actions of buyers and sellers tend to
      move the market toward equilibrium where there is no shortage or surplus is basic
      in the classic and current literature of economics. The problem with subsidies is
      that nurses who receive subsidized educations are able to provide nursing
      services for less compensation because they paid less or nothing for their
      educations. Subsidies may be politically appealing, but they override market
      forces of supply and demand. The demand for nurses and nursing instructors can be
      met and maintained for generations to come with policies that expand roles and
      reimbursement for APNs and encourage the nurse and nursing instructor labor
      markets to correct themselves by providing fair compensation under Magnet status
      working conditions. Politics and policies meant to correct the nursing shortage
      should focus less on how to reduce the cost of producing nurses, and more on how
      to afford to compensate nurses with wages and benefits that achieve market
      equilibrium.

PMID- 18080624
TI  - Effect of guideline implementation on costs of hand hygiene.
AB  - Hands of health care personnel frequently serve as vectors for the transmission
      of organisms between patients and are also a major reservoir for pathogens with
      antimicrobial resistance. Hand hygiene is one effective strategy to reduce health
      care associated infections. The purposes of this study were to (a) compare the
      costs of hand hygiene in hospitals with high and low hand hygiene compliance as
      well as high and low frequency of alcohol hand rub use; and (b) examine
      associations between hospital characteristics and hand hygiene compliance as well
      as frequency of alcohol hand rub use. Nursing and health care policy leaders
      should look for ways to promote sustained adherence to hand hygiene
      recommendations.

PMID- 18080626
TI  - Crossing the quality chasm: creating the ideal patient care experience.
AB  - To create a health system that better meets patients' needs requires a
      fundamental redesign of our care delivery system and a new framework. Without a
      payment mechanism to reflect the value of care provided other than the face-to
      face visit, adoption of advanced medical home principles will be challenging. The
      hand-off of the patient between providers and settings of care is a critical time
      for the patient and its effectiveness impacts patient care outcomes. The
      appropriate utilization of hospital and other health system resources is crucial,
      especially as hospitals, emergency departments, and other health care venues
      increasingly face capacity constraints and throughput challenges. It becomes the
      responsibility of the multidisciplinary team of providers to ensure that patients
      being discharged have an identified personal physician or team who will provide a
      medical home, and that the handoff to this medical home is thorough and well
      coordinated. An ideal patient care experience is one in which all systems and
      processes are geared to meet the needs of the patient: a safety-oriented system
      that provides standardized, evidence-based care supported by technology, but that
      recognizes and responds to individual needs.

PMID- 18080627
TI  - Leadership: social identity and guiding from within.
AB  - An important field in leadership research is that of the social identity of the
      group and what that means for leadership. In health care, there are many
      different types of social identities that vary by hospital, geography, and
      profession. Leaders often sabotage their effectiveness when they do not consider
      the social values of the group. The work of leaders is to help move units and
      organizations to a higher level of performance. Identifying the social identity
      of the group is the first step. The most successful have expertise in assessing
      the social identity of groups and developing a commonality of a shared vision
      that represents the best work of the group and of the leader.

PMID- 18080628
TI  - Social networking: applications for health care recruitment.
AB  - In today's competitive landscape for health care talent, nursing executives and
      human resource professionals need to assess and evaluate new avenues for
      recruitment. The strategy of filling positions by means of print advertising is
      becoming outmoded quickly. As an industry, health care typically lags behind
      other industries when it relates to technology. This is especially true in
      implementing any interactive strategies to target hard-to-fill positions. Social
      networking sites have appeared on the Internet landscape quickly and continue to
      flourish. Nurse leaders need to capitalize on this phenomenon.

PMID- 18080629
TI  - Incorporating the National Guideline Clearinghouse into evidence-based nursing
      practice.
AB  - The National Guideline Clearinghouse (NGC) can be used as a means of integrating
      the constantly growing and changing body of scientific clinical evidence into the
      artful practice of nursing. The NGC offers an extensive collection of peer
      reviewed, current, scientific standards to support clinical decision making in
      nursing practice. Nurse leaders should take a leadership role in bringing these
      relevant resources and new nursing knowledge to policy and procedure committees
      for active consideration.

PMID- 18080630
TI  - Promoting social capital for the elderly.
AB  - The new gold standard has evolved from aging in place to aging in community.
      Having social capital by being an active member of a community has a positive
      effect and can decrease vulnerability to health risk. Federal and state monies
      have been utilized to support community activities for the elderly including the
      first meal programs and moving to community-based assisted living programs. While
      staying in the community is the ideal, a community can be created by progressive
      leadership in a traditional retirement community including a skilled nursing
      home. Retirement communities based on the six dimensions of wellness can create a
      nurturing environment. Nurse leaders can meet the challenge of creating strong
      environments for the elderly.

PMID- 18080631
TI  - [Annual Nurnberg Congress of BeKD (1)].

PMID- 18080632
TI  - ["Learning by doing". Project history of ambulatory nursing of children and
      adolescents of an oncologic department].

PMID- 18080633
TI  - [Migraines and headaches in pediatric nursing practice].

PMID- 18080634
TI  - [Children with cardiac pacemakers. A guideline by the Giessen/Marburg University
      Clinic].

PMID- 18080635
TI  - [Hygiene procedures in pasteurization of breast milk].

PMID- 18080636
TI  - [Planning concept for establishing home nursing care for children and adolescents
      in Tirol].

PMID- 18080637
TI  - [Parents of disabled children. An attachment theory observation].

PMID- 18080638
TI  - [The status of nursing hides a potential for latent violence].

PMID- 18080639
TI  - [7 questions concerning the personal budget].

PMID- 18080640
TI  - [Report of experiences "Between tears, rage and gratitude"].

PMID- 18080641
TI  - [Pediatrician critique: "Our egocentric consumer mentality unfit for
      grandchildren"].

PMID- 18080642
TI  - [Staying awake, but how?].

PMID- 18080643
TI  - Israel National Health Survey: new data for planners, clinicians, researchers and
      the public at large.

PMID- 18080644
TI  - The Israel National Health Survey: initial results and future directions.

PMID- 18080645
TI  - The Israel National Health Survey: issues and methods.
AB  - OBJECTIVE: The Israel National Health Survey--World Mental Health Survey (INHS)
      was designed to collect data on (a) the prevalence of mental disorders; (b) the
      prevalence of impairments and disabilities; (c) chronic conditions, disability,
      physical health, health services utilization and out-of-pocket medical
      expenditure which might be associated with mental disorder; and (d) socioeconomic
      and demographic correlates of mental disorder. This paper presents an overview of
      the methods used in this survey. METHOD: The INHS was a cross-sectional survey
      based on a representative sample of 5,000 adults, 21 years or older, from the
      general population of Israel. The Composite International Diagnostic Interview
      (WMH-CIDI) was administered in face-to-face interviews at the respondents' homes
      between May, 2003, and April, 2004, using computer assisted personal interview
      (CAPI) technology. RESULTS: The overall response rate was 72.6%. CONCLUSION: The
      methodology and the quality control procedures used have made the INHS database a
      unique source of information about the prevalence, disability burden and unmet
      health needs of people suffering from common mental disorders and substance
      disorders in Israel.

PMID- 18080646
TI  - Prevalence of mood and anxiety disorders in the community: results from the
      Israel National Health Survey.
AB  - OBJECTIVE: To estimate the 12-month and lifetime prevalence rates of mood and
      anxiety disorders in Israel and their socio-demographic correlates. METHOD: A
      representative sample of respondents extracted from the National Population
      Register of non-institutionalized residents, aged 21 or older, were interviewed
      at home between May, 2003, and April, 2004. DSM-IV disorders were assessed using
      a revised version of the Composite International Diagnostic Interview. RESULTS:
      Seventeen percent of the sampled adult population reported a lifetime occurrence
      of a mood or anxiety disorder, while nearly one in 10 (9.7%) reported a mood or
      anxiety disorder occurring during the previous 12 months. Mood disorders were
      twice as common as anxiety disorders. CONCLUSION: Contrary to expectations born
      out of Israel's unique life circumstances, the prevalence of mood or anxiety
      disorders fall within the range of other western countries. However, given the
      current age structure and the age of onset of these disorders, their total burden
      in the near future is likely to increase.

PMID- 18080647
TI  - Common mental disorders among Arab-Israelis: findings from the Israel National
      Health Survey.
AB  - OBJECTIVES: Psychiatric epidemiological data on Arab populations are generally
      scanty. This community-based survey, a component of the World Health
      Organization's 27-country study, explored the prevalence rates of anxiety and
      mood disorders, emotional distress and help-seeking practices among Arab
      Israelis, and compared them with those found among Jewish-Israelis. METHODS:
      Close to 5,000 non-institutionalized individuals were interviewed with the
      WHO/Composite International Diagnostic Interview (CIDI) to determine the
      prevalence rates of selected psychiatric diagnoses, and with the 12-item General
      Health Questionnaire (GHQ) to measure emotional distress. The schedule included
      other items, e.g., socio-demographic variables and help-seeking practices.
      RESULTS: Arab-Israelis, in contrast to Jewish-Israelis, had higher mean GHQ-12
      scores and lower self-appraisal of mental health. Twelve-month prevalence rates
      for any anxiety or affective disorder were not significantly higher among Arab
      Israelis. Among respondents with diagnosed disorders, rates of help-seeking from
      specialized health services were lower among Arab-Israelis than among Jewish
      Israelis. Intention to consult was elicited from both groups when the disorders
      were accompanied by higher distress scores. CONCLUSIONS: Despite major health
      gains, the social stresses impacting the Arab-Israeli minority may explain both
      the higher emotional distress and lower self-appraisal of mental health. However,
      no impact was observed of social causation factors on the rates of common mental
      disorders in the Arab-Israeli group. Cultural factors, including the definition
      of disorders and stigma and a lesser availability of culturally-tailored
      services, could account for the marked treatment gap.

PMID- 18080648
TI  - Twelve-month service utilization rates for mental health reasons: data from the
      Israel National Health Survey.
AB  - OBJECTIVE: To measure the 12-month utilization rates for mental health reasons in
      all types of services. METHOD: A representative sample extracted from the
      National Population Register of non-institutionalized residents aged 21 or older
      were interviewed at their homes between May 2003 and April 2004. DSM-IV disorders
      were assessed using a revised version of the Composite International Diagnostic
      Interview (WMH-CIDI). RESULTS: About 10% of the adult population receives some
      type of treatment for emotional or mental health problems within a single year.
      More than half of service consumers were not classified as suffering from mood or
      anxiety disorders. Of those diagnosed with mood or anxiety disorders in the past
      12 months only about 50% used any type of service for mental health problems.
      CONCLUSION: There is only a partial overlap between those who utilize the
      services and those who meet the criteria for a clinical diagnosis of mental
      disorder.

PMID- 18080649
TI  - Alcohol drinking patterns and prevalence of alcohol-abuse and dependence in the
      Israel National Health Survey.
AB  - BACKGROUND: Coexistence of disparate religious/cultural mores with regard to
      alcohol drinking within the changing social milieu of Israel provides an
      informative environment for investigation of alcohol consumption patterns and
      alcohol-related mental disorders. METHOD: A national population-based survey of
      Israeli adults was conducted as part of the WHO/World Mental Health Survey
      initiative. Logistic regression models accommodated the complex sampling design
      and accounted for potential confounders. RESULTS: Half of the 4,859 respondents
      reported any alcohol consumption in the year prior to interview; 5% drink 3 or
      more times weekly. DSM-IV criteria for alcohol-abuse or dependence (lifetime)
      were met by 4.3% of respondents. Significantly higher rates were found among
      males (AOR, adjusted odds ratio=7.3), younger adults (AOR=5.0), immigrants from
      the former Soviet Union (AOR=2.0), and those who were never married (AOR=1.6).
      LIMITATIONS: Under-reporting remains a potential concern in health behavior
      surveys, particularly in the face of opposing religious norms. CONCLUSIONS: The
      lifetime prevalence of alcohol abuse in Israel is identical to other European
      countries while drinking levels are considerably lower, suggesting a biological
      sensitivity alongside socio-cultural factors.

PMID- 18080650
TI  - Suicide ideation, planning and attempts: results from the Israel National Health
      Survey.
AB  - OBJECTIVES: To establish the lifetime prevalence rates of suicide ideations,
      plans and attempts, and to identify the conditional risks of suicide attempts
      following the prior onset of suicide ideation or planning. METHOD: A
      representative sample extracted from the National Population Register of non
      institutionalized residents, aged 21 or older, were interviewed at home between
      May 2003 and April 2004 using the Composite International Diagnostic Interview
      which included questions on suicide ideations, plans and attempts The final
      sample included 4,859 respondents. RESULTS: About 5.5% of the adults reported
      that they have thought of suicide, and 1.4% that they have attempted to commit
      suicide during their lifetime. The year following the onset of ideation
      constitutes the year of highest risk for suicide attempt. CONCLUSION: The risk of
      suicide attempt is highest among individuals with mental health disorders, while
      the transition from suicide ideation to suicide attempt among them is more likely
      to be planned. The youngest age group has the highest odds of suicide attempts
      and the highest odds of impulsive suicide attempts.

PMID- 18080651
TI  - Psychopathology and other health dimensions among the offspring of Holocaust
      survivors: results from the Israel National Health Survey.
AB  - BACKGROUND: Holocaust survivors show long-lasting psychopathological wounds and
      scars. The experiences they endured during WWII were thought to impair their
      parental functioning. A trans-generational transmission of the trauma has been
      reported by clinicians and by researchers exploring the vulnerability of the
      adult offspring when facing major stressful events. However, the two previous
      epidemiological studies conducted so far failed to show enhanced psychopathology
      when the children of the Holocaust survivors were compared with suitable
      controls. METHODS: In the Israel-component of the World Mental Health Survey
      offspring of Holocaust survivors were identified (N=430) and compared to
      offspring of Europe-born parents who did not reside in Nazi-occupied countries
      (N=417) on several measures of psychopathology and physical health dimensions
      that have a marked psychological components, and on health and mental health help
      seeking practices. RESULTS: No statistical differences were elicited between both
      groups on all those domains. CONCLUSIONS: Apparently, Holocaust survivor parents
      succeeded to spare their children from the untoward consequences of the
      psychological wounds and scars of their traumatic past. Survivors strived to
      secure a better and safer life for their children as evidenced by the relatively
      higher level of education that the offspring of the survivors were able to
      achieve than the comparison group, although their own educational career was
      truncated. Also, separations from parents until the end of adolescence of the
      children did not differ between the two

PMID- 18080652
TI  - Psychiatric epidemiology in Israel, 2007: reflections on the Israel National
      Health Survey.

PMID- 18080653
TI  - The emergence of a new interdiscipline: oncofertility.

PMID- 18080654
TI  - Fertility management for women with cancer.
AB  - With time, great strides are being made in the care of cancer sufferers. The
      longevity and quality of life of these unfortunate individuals continues to
      improve and the word "cure" is more commonly being heard. In a similar manner,
      there is also much reason for optimism regarding the future fertility options for
      patients with cancer as well as for those with other diseases that have a high
      likelihood of rendering a female infertile prior to completing her family. Figure
      2.4 outlines the various cryopreservation technologies currently available. While
      IVF and embryo freezing remain the gold standard at the present, refinements in
      in vitro maturation of oocytes and cryopreservation of oocytes and ovarian cortex
      will lead to improved results and availability of these technologies. Counseling
      patients of child-bearing age or their parents regarding future fertility when
      faced with a life-threatening cancer diagnosis is difficult but extremely
      important. With modern approaches to cancer care, survival rates have improved
      significantly. Therefore, the health care team has a responsibility to provide
      screening to identify these patients, provide education so that an informed
      decision can be made as rapidly as possible, and have a team ready to preserve
      fertility once a decision has been made. With the improvements in fertility
      outcomes for these patients, appropriate education of key communities, including
      cancer sufferers and their health care providers, will be necessary to ensure
      that the issue of fertility after cancer is at least discussed and offered to
      those in whom it is appropriate.

PMID- 18080655
TI  - Fertility preservation in adult male cancer patients.

PMID- 18080656
TI  - Managing fertility in childhood cancer patients.

PMID- 18080657
TI  - Fertility risk in pediatric and adolescent cancers.

PMID- 18080658
TI  - Bioengineering and the ovarian follicle.

PMID- 18080659
TI  - The science of cryobiology.

PMID- 18080660
TI  - Ovarian tissue cryopreservation and transplantation: banking reproductive
      potential for the future.

PMID- 18080661
TI  - Progress, history and promise of ovarian cryopreservation and transplantation for
      pediatric cancer patients.

PMID- 18080662
TI  - Oncofertility and the social sciences.

PMID- 18080663
TI  - Shared decision making: fertility and pediatric cancers.

PMID- 18080664
TI  - Today's research, tomorrows cures: the ethical implications of oncofertility.

PMID- 18080665
TI  - The psychosocial context of cancer-related infertility.

PMID- 18080666
TI  - Childhood cancer: fertility and psychosocial implications.

PMID- 18080667
TI  - Fertility preservation and adolescent cancer patients: lessons from adult
      survivors of childhood cancer and their parents.

PMID- 18080668
TI  - Oncofertility: a new medical discipline and the emerging scholar.

PMID- 18080670
TI  - Personal accounts of cancer and infertility.

PMID- 18080669
TI  - Oncofertility consortium consensus statement: guidelines for ovarian tissue
      cryopreservation.

PMID- 18080671
TI  - Influenza virus and redox mediated cell signaling: a complex network of
      virus/host interaction.
AB  - Several viruses, including influenza, induce an imbalance of intracellular redox
      state toward pro-oxidant conditions. Through different mechanisms these
      alterations contribute both to influenza virus replication and to the
      pathogenesis of virus-induced disease. At the same time, influenza virus
      activates several intracellular signaling pathways involved in important
      physiological functions of the cell. Interestingly, many of these pathways are
      finely regulated by small changes in intracellular redox state, and the virus
      induced redox imbalance might also control viral replication through this
      mechanism. Here we review the main intracellular redox-sensitive pathways
      activated upon influenza infection and involved in regulating viral replication.

PMID- 18080672
TI  - Genetic variability in E6 and E7 genes of human papillomavirus -16, -18, -31 and 
      33 from HIV-1-positive women in Italy.
AB  - Among 544 HIV-positive women screened for HPV-DNA between 2003 and 2005, 265
      (48.7%) were HPV-positive: 24 (9.1%) harboured HPV-16, 21 (7.9%) HPV-31, 12
      (4.5%) HPV-18, 7 (2.6%) HPV-33. E6 and E7 of these HPV types were sequenced to
      assess their diversity. Ranges of inter- and intra-variant diversity were 1.2-3
      3%, and 0.8-1.8 for E6 and 0.6-2.7%, and 0.6-2.0% for E7, respectively. HPV-31,
      the second most common HPV type, showed the highest diversity for both regions.
      On the whole, 26 out of 59 mutations were non-synonymous. The variability of
      these proteins may have implications in HPV vaccine strategies.

PMID- 18080673
TI  - The human bocavirus role in acute respiratory tract infections of pediatric
      patients as defined by viral load quantification.
AB  - The major objective of this study was to investigate the pathogenic role of human
      bocavirus (hBoV) in patients hospitalized with acute respiratory tract infection
      (ARTI). Overall, 685 respiratory samples from 426 patients were examined by PCR
      for human bocavirus, as well as for other known human respiratory viruses. HBoV
      was quantified by PCR. Forty/283 (14.1%) pediatric patients, and 2/143 (1.4%)
      adult patients were found to harbor hBoV for a total of 45 episodes (16 detected
      as single infection, and 29 as coinfection) of hBoV-associated respiratory
      infection. HBoV DNA quantification revealed the presence of an NPA viral load >
      1.0 x 10(5) DNA copies/ml in respiratory secretions from 17/40 (42.5%) children
      and 0/2 adults. Below this cut-off, hBoV appeared to be an innocent bystander or
      a persistent virus. Although hBoV may be frequently detected in children with
      upper or lower ARTI, in less than 50% young patients it appears to be potentially
      pathogenic.

PMID- 18080674
TI  - Evaluation of three different assays for the assessment of Epstein Barr Virus
      immunological status.
AB  - Various attempts have been made to improve Epstein Barr Virus serodiagnosis by
      developing convenient methods. The present study evaluated the performance of
      multiplexed bead assays and immunoblot based assays on automated platforms by
      comparing them with immunofluorescence based assays for the determination of EBV
      immune status. A total of 45 serum samples were included in the study. Serum
      samples were tested by multiplexed bead EBV assays (AtheNA Multi-Lyte, Zeus
      Scientific,USA) and immunoblot based assays (Euroline, Euroimmun AG, Germany) on
      automated platforms. Assay systems were evaluated by comparing them with
      immunofluorescence based assays (Zeus Scientific, USA). For EBV anti-VCA IgM,
      anti-VCA IgG, anti-EA and anti-EBNA, the kappa values reflecting agreements of
      AtheNA and IFA were 0.20, 0.54, 0.92 and 0.95 for anti-EA, anti-VCA IgG, anti-VCA
      IgM and anti-EBNA respectively and the agreements of Euroline and IFA were 0.53,
      0.67, 0.81 and 1.000 for anti-VCA IgG, anti-EA, anti-VCA IgM and anti-EBNA
      respectively. The results of the study performed on a limited number of serum
      samples demonstrated that the multiplexed bead assays and immunoblot assays agree
      with the standard IFA assay for anti-EBNA IgG and anti-VCA IgM detection while
      the agreement is less for anti-EA and anti-VCA IgG.

PMID- 18080675
TI  - Evaluation of a genotyping method based on the ospA gene to detect Borrelia
      burgdorferi sensu lato in multiple samples of lyme borreliosis patients.
AB  - In this study we have developed a new Restriction-Fragment-Length-Polymorphism
      (RFLP) genotyping method for rapid detection and identification of Borrelia
      genospecies present as unique species or as co-infection in multiple specimens
      obtained simultaneously from 29 individual patients affected by early or late
      Lyme borreliosis (LB). The target of the RFLP-genotyping was the heterogeneous
      plasmid located ospA gene, thus we developed a method able to detect and
      differentiate between six clinically relevant Borrelia genospecies circulating in
      Europe, B. burgdorferi sensu stricto, B. garinii, B. afzelii, B. valaisiana, B.
      bissettii and B. spielmanii. In this study Borrelia DNA could be detected by PCR
      in at least one specimen of each patient, except in one case of neuroborreliosis
      (NB); blood samples gave the highest sensitivity in all patient groups. The
      genotyping indicated that B. afzelii was present in 8 patients with skin
      involvement, B. garinii in 2 cases of NB and 4 cases with skin involvement, B.
      burgdorferi sensu stricto was detected in one patient with skin involvement and
      another with Lyme arthritis. Different Borrelia species in distinct specimens
      were identified in one patient with EM. The RFLP analysis of 11 patients revealed
      mixed patterns, which suggested pluri-infection with different Borrelia species.

PMID- 18080676
TI  - Activities of Linezolid against nontuberculous mycobacteria.
AB  - The activity of linezolid (Pfizer, USA) was tested by broth microdilution against
      53 clinical isolates of non-tuberculous mycobacteria (NTM), including the common
      disease producing species Mycobacterium avium, M. intracellulare, M. fortuitum,
      M. chelonae and M. abscessus, obtained from western Turkey. The isolates of M.
      abscessus and M. intracellulare were the least susceptible, M. mucogenicum, M.
      gordonae and M. avium were the most susceptible to linezolid of the common
      species of NTM. Linezolid showed a variable sensitivity in all strains;
      therefore, each species and strain must be individually evaluated, and it is
      always advisable to perform in vitro sensitivity tests before using the drug for
      human therapy.

PMID- 18080677
TI  - Development and clinical validation of a real-time PCR using a uni-molecular
      Scorpion-based probe for the detection of Mycoplasma pneumoniae in clinical
      isolates.
AB  - Mycoplasma pneumoniae (Mp) is a frequent cause of Community Acquired Pneumoniae
      (CAP). The etiological role of Mp is usually suspected using serological assays,
      but the detection of specific anti-Mp antibodies becomes possible only 1-2 weeks
      after the primary infection. On the contrary, direct diagnosis using real-time
      PCR allows an efficient detection of Mp DNA in all the phases of the infection
      and particularly during early serum negative periods. In this study, we developed
      a novel Scorpion-probe real-time PCR-based assay. The probe's uni-molecular
      structure offers thermodynamic advantages owing to its kinetic reaction,
      providing faster performances compared to a TaqMan-based assay, but maintaining
      the same sensitivity and specificity. The Scorpion-based assay was employed on
      388 clinical samples and compared with conventional qualitative PCR and
      serological tests. It was found more sensitive because it also allowed the
      detection of Mp in specimens found negative using classic qualitative PCR, but
      displaying seropositivity or a later seroconversion.

PMID- 18080678
TI  - Emergence of fluoroquinolone resistance in Escherichia coli isolates at the
      department of clinical hematology.
AB  - The aim of this study was to evaluate the dependence of Escherichia coli
      resistance to fluoroquinolones on their use in the outpatients and inpatients in
      the Hradec Kralove region of the Czech Republic. Data on inpatient
      fluoroquinolones use were obtained from the database of the Charles University
      Teaching Hospital Pharmacy and expressed as defined daily dose per 100 beds -
      days (DBD). Data on outpatient prescriptions were obtained from the database of
      the General Health Insurance Company and expressed in defined daily doses per
      1000 clients per day (DID). Escherichia coli strains were isolated from samples
      of urine of both community and hospitalized patients suffering from acute
      bacterial urinary tract infection, examined using aerobic cultivation, and
      determined by standard biochemical procedures. The utilization of
      fluoroquinolones in inpatients has significantly (p < 0.01) increased from 2.73
      DBD in 2001 to 4.89 DBD in 2006. In outpatients, fluoroquinolone utilization has
      also increased significantly from 0.29 DID to 1.15 DID (p < 0.01). In the same
      period, 11,856 Escherichia coli strains were isolated from inpatients and
      outpatients with urinary tract infection and tested for the susceptibility to
      fluoroquinolones. Resistance increased significantly (p < 0.01), both in the
      hospital (from 2% to 10%) and in the community (from 1% to 11%). The development
      of Escherichia coli resistance to fluoroquinolones correlates significantly with
      their utilization both in hospital (r = 0.996, p = 0.005) and in the community (r
      = 0.878, p = 0.029). Results of this study shows the impact of fluoroquinolone
      utilization on Escherichia coli resistance, and support the need of controlled
      use of these effective antibiotics.

PMID- 18080679
TI  - Microbiological evaluation of the effects of hyperbaric oxygen on periodontal
      disease.
AB  - The term periodontitis indicates a variety of clinical manifestations of
      infectious disorders in which the supporting tissues of the teeth are attacked.
      The initiation and progression of periodontal disease are attributed to the
      presence of elevated levels of pathogenic bacteria within the gingival crevice.
      Approaches to periodontal treatment range from surgical to regenerative therapy
      and anti-infective chemotherapy. Anti-infective drug therapy should be rationally
      based on the composition of the pathogenic microbiota. It is also important to
      recognize that the periodontopathic plaque constitutes a bacterial biofilm
      infection that may render the resident microorganisms more resistant than the
      same organisms grown planktonically. Hyperbaric oxygen (HBO) has been
      successfully used in several medical applications. The therapeutic effect is
      related to elevated partial oxygen pressure in the tissues. The aim of this study
      was to evaluate the effects of HBO on a selected number of patients suffering
      from adult chronic periodontitis in comparison with surgical intervention
      (scaling and root planning, SRP), as well as the effects of a combination of both
      therapies on the evolution over time of the microflora of the periodontal
      pockets. Bacteria were detected either by culture or by a molecular method (PCR).
      Microbiological data indicate that the combination of HBO and SRP substantially
      reduced (by up to 99.9%) the gram-negative anaerobe loads of the subgingival
      microflora. The low values of pathogens persisted for at least two months after
      the therapy. HBO or SRP alone produced a temporarily more limited effect on
      periodontal anaerobes. Additional experimental confirmation of these results was
      provided by molecular detection of the main periodontopathogenic bacteria with a
      significant reduction in the number of dental sites which harboured them. It is
      also shown that HBO both alone and in combination with SRP reduced the Gingival
      Index value to zero and gingival health persisted for 3 months at least. Thus, in
      parallel with the loss of periodontopathogenic bacteria, a substantial
      improvement in oral health was observed. In conclusion, this study has shown that
      HBO may represent a useful aid, especially in combination with SRP, as far as non
      surgical periodontal therapy is concerned.

PMID- 18080680
TI  - In vitro and in vivo activities of Haplophyllum myrtifolium against Leishmania
      tropica.
AB  - This study aimed to evaluate the in vitro and in vivo leishmanicidal activity of
      an endemic Turkish plant and compare its efficacy with a reference drug. In
      addition to the in vitro activities of the ethanol, acidified and alkaloid
      extracts and furoquinoline alkaloids skimmianine and gamma-fagarine, in vivo
      antileishmanial activitiy of the acidified extract of Haplophyllum myrtifolium
      Boiss. (Rutaceae) were investigated against Leishmania tropica (L. tropica), a
      causative agent of cutaneous leishmaniasis. All the extracts and pure compounds
      showed in vitro inhibitory activity against the promastigotes of. L. tropica. The
      in vitro 50% inhibitory concentrations of y-fagarine, acidified extract, ethanol
      extract, skimmianine and alkaloid extract against promastigotes were determined
      as 8.7, 9.4, 10.9, 25.7 and 25.8 microg/ml respectively. In vivo results of
      Haplophyllum myrtifolium acidified extract showed that this plant has a limited
      effect on decreasing the lesion size of experimental mice infected with
      Leishmania tropica. To the best of our knowledge, this is the first time both the
      in vitro and in vivo antileishmanial activity of Haplophyllum mrytifolium have
      been reported in the same research.

PMID- 18080681
TI  - Immunomodulatory effects of bovine colostrum in human peripheral blood
      mononuclear cells.
AB  - Human and bovine colostrum (BC) contain a remarkable amount of bioactive
      substances, including antibodies towards many common pathogens of the intestinal
      and respiratory tract as well as growth factors, vitamins, cytokines and other
      proteic, lipidic and glucidic factors. In this study we investigated whether BC
      had any immunomodulatory effect on human peripheral blood mononuclear cells
      (PBMC) from healthy donors. To this aim we focused on the production of IL-12 and
      IFN-gamma, cytokines involved in the Th1 polarization required for a successful
      immune response towards intracellular pathogens, such as bacteria and viruses. BC
      induced a dose-dependent production of IL-12 by CD14+ monocytes, but was unable
      to induce IFN-gamma production. However, BC differentially affected stimuli
      induced IFN-gamma production: it enhanced IFN-gamma in response to weak antigenic
      stimulation and it inhibited IFN-gamma in response to strong antigenic
      stimulation. These effects were not dose-dependent. We also measured PBMC
      proliferation, which was substantially unaffected by BC. Our data suggest that
      the Th1-promoting activity of BC could contribute, together with the antibodies,
      to the protective effect of BC on the offspring. BC could also represent an
      inexpensive therapeutic tool in prevention and treatment of several human
      microbial infections, including influenza.

PMID- 18080682
TI  - Etiological investigation of multiple respiratory infections in cats.
AB  - In order to evaluate the relevance of multiple infections in domestic cats with
      Upper Respiratory Tract Disease (URTD) one hundred animals with clinical signs
      were investigated for detection of Feline Herpesvirus type-1 (FHV-1),
      Chlamydophila felis, Feline Calicivirus (FCV) and Bordetella bronchiseptica from
      mucosal swabs. Forty-seven cats were positive for FCV, 42 cats for FHV-1, 26 for
      B. bronchiseptica and 8 for C. felis. Dual or multiple infections were found in
      33 of examined animals. Our results document that FCV and FHV-1 are the major
      recognized cause of URTD, although infections associated with other pathogens
      such as B. bronchiseptica or C. felis are also common in cats.

PMID- 18080683
TI  - Antimicrobial activity of a formulation for the low temperature disinfection of
      critical and semi-critical medical equipment and surfaces.
AB  - The antimicrobial activity of the disinfectant formulation UMONIUM38 (Isopropyl
      tridecyl-dimethyl-ammonium; Huckert's International, Nivelles, Belgium) planned
      for the low temperature disinfection of critical and semi-critical medical
      equipment and surfaces was evaluated under clean and dirty experimental
      conditions (high and low concentrations of organic material). The formulation was
      obtained by a synergic combination of three different active compounds, two
      alcohols and a quaternary ammonium. The anti-mycobacterial (Mycobacterium avium
      and Mycobacterium terrae), and antiviral (Poliovirus type 1, Adenovirus type 5,
      hepatitis B virus, and human immunodeficiency virus type 1) activities of this
      formulation were addressed using suspension assays. In addition, surface assays
      were also used to test the antibacterial (Pseudomonas aeruginosa, Escherichia
      coli, Staphylococcus aureus, Enterococcus hirae) and antimycotic (Candida
      albicans and Aspergillus niger) activities. The data document the dynamics of the
      antimicrobial activity under in vitro controlled conditions and highlight the
      relatively low influence of organic material on its activity.

PMID- 18080684
TI  - Enteric viruses in molluscan shellfish.
AB  - One hundred and thirty-seven bivalves were collected for environmental monitoring
      and the market; all the samples were analysed by RT-PCR test. Bacteriological
      counts meeting the European Union shellfish criteria were reached by 69.5% of all
      the samples, whereas the overall positive values for enteric virus presence were:
      25.5%, 18.2%, 8.0% and 2.1% for Rotavirus, Astrovirus, Enteroviruses, Norovirus,
      respectively. Mussels appear to be the most contaminated bivalves, with 64.8% of
      positive samples, 55.7% and 22.7% respectively for clams and oysters, whereas in
      the bivalves collected for human consumption 50.7% were enteric virus positive,
      as compared to 56.4% of the samples collected for growing-area classification.
      The overall positive sample was 54.0%.

PMID- 18080685
TI  - QuantiFERON TB Gold: a new method for latent tuberculosis infection.
AB  - QuantiFERON-TB Gold obtained approval in 2003 by the Food and Drug Administration
      as a valid tool for the diagnosis of latent tuberculosis. In this report, we
      evaluated its potential use in the immunological diagnosis of Mycobacterium
      tuberculosis infections in different groups of subjects. Our data indicate that
      QuantiFERON-TB Gold is specific for identifying subjects who have come into
      contact with M. tuberculosis and its use alongside traditional diagnostic
      techniques may be an important instrument for controlling tuberculosis.

PMID- 18080686
TI  - Clostridium baratii bacteremia associated with Kawasaki syndrome. First case
      report.
AB  - We experienced a case of a 3-year-old boy who presented signs and symptoms of
      Kawasaki syndrome. Two blood culture sets were processed by the hospital
      microbiology laboratory using a standard blood culturing system. The anaerobic
      bottles gave a positive result at day 3 after inoculation. The biochemical
      profiles produced by the RapID ANA II System showed that the organism was
      Clostridium baratii with a probability of 99%. Our case highlights the importance
      of C. baratii as a potential human pathogen and reports the associations with
      manifestations, which, to our knowledge, have not been previously described
      concomitantly with a clostridial infection.

PMID- 18080687
TI  - [Anticancer drugs used in medicine and being in clinical research].
AB  - Tumor diseases are most serious issue of clinical medicine and pharmacology. The
      coordination compounds of platinum (II) are fundamental group of drugs used in
      antineoplastic therapy and cisplatin is the first antitumor specimen used in
      health care. Cisplatin is used in treatment for e.g. ovarian carcinoma,
      microcellular and no microcellular pulmonary carcinoma, orchiencephaloma, neck
      and esophagus carcinoma. Carboplatin is the second specimen applied in tumors'
      therapy. Both the coordination compound of platinum (II) possesses similar
      antineoplastic action but have a different effectiveness of activity and
      toxicity. It's very important for contemporary medicine to create new effective
      cytotoxic compounds of platinum with better clinical tolerance.

PMID- 18080688
TI  - [One-year follow-up of TSH level and thyroid volume in patients with bone marrow
      or peripheral blood hematopoietic stem cell transplantation following
      chemotherapy].
AB  - Bone Hematopoietic Stem Cell Transplantation (HSCT) following high-dose chemo-
      and radiotherapy became treatment of choice in various numbers of hematological
      and hereditary or acquired immune disorders. Protocols preparing to allogenic
      transplantation have a few aims: eradication of neoplastic disease, suppression
      of defense system of recipient (reduction of transplant rejection), preparation
      of bone marrow microenvironment to implantation donor's cells. Chemotherapy is
      combined with acute side effects as nausea, vomiting, diarrhea, hair loss,
      mucositis, and hemorrhagic cystitis. Late toxic effects also appear, it require
      prolonged observation and care. Among them most common is dysfunction of thyroid
      and gonads in adults and growth inhibition in children. The aim of this study was
      prospective evaluation of thyroid function in adults with autologous and
      allogeneic BMT or HSCT following myeloablative chemotherapy. MATERIAL AND
      METHODS: 23 patients (16 females and 7 males) treated in Department of Hematology
      and Transplantology Medical University of Gdansk were included. Average age was
      34.3 years with range from 17-50 years. Each patient had endocrinological
      interview, physical examination of thyroid, TSH level assessment and
      ultrasonographic thyroid volume measurement before HSCT Identical control
      examinations were performed in third and twenty month after transplantation. TSH
      level and thyroid volume were tested for significant differences before and after
      transplantation using paired t-tests. A P-value of < 0.05 was considered
      statistically significant. RESULTS: 12 months after HSCT following myeloablative
      chemotherapy we noted on average decrease in volume of thyroid from 17,5 ml to
      13.5 ml (females to 9.7 ml). This difference was statistically significant with p
      = 0.002. Also 12 months after the procedure progressive rise in TSH level was
      noted from 2.0 mU/l to 3.2 mU/l. Nevertheless this tendency was not statistically
      significant with p = 0.08. CONCLUSIONS: We suggest control of TSH, fT4 level and
      thyroid ultrasound examination at least twice--before and 12 months after
      transplantation. Myeloablative chemotherapy before HSCT may cause early (after 3
      months) hypothyroidism--it may last one year after procedure. In case of high TSH
      level we suggest individually adapted L-thyroxine replacement therapy.

PMID- 18080689
TI  - [Concentration of soluble forms of selectins in serum and in cerebrospinal fluid
      in group of patients with neuroborreliosis--a preliminary study].
AB  - The results of the research already done, suggest an important role of selectins
      in inflammatory process of various etiology. Lack of selectins or their ligands
      causes severe complications, such as chronic inflammatory processes. The aim of
      this study was to analyze the role of selectins sL, sE and sP in the development
      and course of neuroborreliosis in the form of meningitis. We have also analyzed
      the influence of treatment on changes of selectins' concentration in serum and
      cerebrospinal fluid. MATERIAL AND METHODS: We have analyzed 17 patients with
      neuroborreliosis presenting as meningitis, in whom we measured by immunoenzymatic
      method concentration of selectins sL, sP and sE in blood and cerebrospinal fluid
      before and after 4-week therapy with cefotaxim. We used Human sL-selectin, Human
      sE-selectin and Human sP-selectin kits produced by Bender Med. Systems, Austria.
      Control group for measurement of concentration of selectins in serum consisted of
      8 healthy patients. Control group for measurement of concentration of selectins
      in cerebrospinal fluid consisted of 8 patients, in whom lumbar puncture excluded
      inflammatory disease of the central nervous system. RESULTS: In serum
      concentration of selectins sL and sP was significantly higher comparing to
      control group. After treatment concentration of these selectins decreased, but
      still was significantly higher than in control group. Only concentration of
      selectin sE was significantly lower than in control group and after treatment
      decreased further remaining lower comparing to control group. In cerebrospinal
      fluid concentration of selectin sL was significantly higher comparing to control
      group and increased after treatment. Concentration of selectins sE and sP
      increased before treatment and decreased after treatment, but still remained
      elevated comparing to control group. CONCLUSIONS: Persistence of increased
      concentration of selectins sP and sL in serum and also of selectin sE in
      cerebrospinal fluid in patients with neuroborreliosis after completed antibiotic
      therapy and regression of clinical symptoms can suggest permanence of chronic
      inflammatory state in consequence of survival of B. burgdorferi spirochetes in
      affected tissues.

PMID- 18080690
TI  - [Clinical assessment of the closure of a temporary diverting ileostomy].
AB  - Closure of the temporary diverting ileostomy is technically easy procedure but
      may have its own side effects, such as obstruction and anastomotic leak. The aim
      of this study was designed to assess the results of the closure of the protective
      ileostomy in the group of patients' operated on for inflammatory bowel disease
      and other inflammatory conditions with inflammatory exudate and to compare them
      with those who underwent surgery for uncomplicated colorectal cancer and
      precancerous conditions. Radiological examination of the efferent ileostomy loop
      was performed preoperatively to assess its influence on surgical strategy and
      postoperative complications resulting from the disturbances of passage of the
      intestinal contents. MATERIAL AND METHODS: This is a retrospective review of 48
      patients divided into 2 groups: patients who suffered from inflammatory bowel
      disease or peritonitis (group I, n = 16) and patients with uncomplicated
      malignant disease or precancerous conditions of the gastrointestinal tract (group
      II, n = 32). Moreover, 18 patients (group A) without preoperative radiological
      assessment were compared with 30 patients (group B) in whom such examination was
      carried out. Statistical analysis was performed by using of the U-Mann-Whitney,
      the Fisher's exact and Student's t-tests. The differences were considered
      significant for levels of less than 0.05. RESULTS: Postoperative complications
      (obstruction and anastomotic dehiscence) occurred in 9 patients (18.7%). Seven
      patients (14.6%) were reoperated on: 6 patients in group 1 (37.5%) and 1 patient
      in group II (3.1%), (p = 0.013). Out of all postoperative complications that
      required secondary surgery, 22.2% of them occurred in patients who did not have
      preoperative radiological examination performed and 10% of them had patients in
      whom radiological assessment was done. Radiological findings revealed efferent
      ileostomy loop stenosis in 4 patients (13.3%) what influenced the operative
      strategy. CONCLUSIONS: Postoperative complications rate was high (18.7%). Closure
      of the temporary diverting ileostomy in patients with inflammatory bowel disease
      or any other inflammatory conditions within the peritoneal cavity are at the
      increased risk of complications than in those with malignant diseases or
      precancerous conditions. Preoperative radiological examination of the efferent
      ileostomy loop is useful in planning of surgical approach and influences improved
      treatment results.

PMID- 18080691
TI  - [The effect of nonsteroidal anti-inflammatory drugs on oxidative/antioxidative
      balance].
AB  - Arachidonic acid cascade activated by cyclooxygenase is an important source of
      reactive oxygen species. Nonsteroidal anti-inflammatory drugs (NSAIDs) can shift
      an oxidative-antioxidative balance towards antioxidation by inhibiting
      cyclooxygenase. The aim of the study was to assess the influence of nonsteroidal
      antiinflammatory drugs on the oxidative-antioxidative balance using animal model.
      MATERIAL AND METHODS: . In the study acetylsalicylic acid (ASA) as COX-1 and COX
      2 inhibitors, and nimesulide as selective COX-2 inhibitor were used. An
      investigation was carried out on rats (of both sex), divided into two groups of
      ten animals each. Rats were given intragastrically for three weeks:
      acetylsalicylic acid (ASA) at doses of 2 and 10 mg/kg bw/day diclofenac at doses
      of 1 and 5 mg/kg bw/day, and nimesulide at doses of 2.5 mg and 12.5 mg/kg bw/day.
      Control group received water. Total antioxidant capacity, nitrotyrosine and TBARS
      in plasma, sulfhydryl groups in whole blood, and thiobarbiturate (TBARS) in
      hemolysates of erythrocytes concentrations were assessed. RESULTS: The applied
      doses of diclofenac significantly increased TBARS and nitrotyrosine
      concentrations and decreased total antioxidant capacity whereas ASA quite the
      opposite: decreased TBARS and nitrotyrosine concentrations and increased total
      antioxidant capacity. Nimesulide only at the dose of 12.5 mg/kg bw/day caused a
      decrease in plasma TBARS and nitrotyrosine concentration. CONCLUSION: This study
      demonstrated the potential antioxidant properties of ASA and nimesulide but not
      the other non-selective NSAIDs--diclofenac which turned out to exert pro
      oxidative effects. ASA appears to possess stronger antioxidant activity than
      nimesulide.

PMID- 18080692
TI  - [Correlation of membrane type I matrix metalloproteinase (MT1-MMP) expression
      with clinicomorphological features of tumor front in squamous cell carcinoma of
      the larynx].
AB  - Matrix metalloproteases (MMPs) are proteolytic enzymes contribute to tumor
      expansion by degrading components of the extracellular matrix. MPPs play a key
      role in tumor invasion and metastases of various cancers and head and neck
      carcinoma as well. The aim of this study was to investigate MT1-MMP expression in
      squamous cell carcinoma of the larynx to relate these levels of expression to
      clinicohistological features of the tumor and lymph nodes e.g. TNM, nodal
      micrometastases, tumor front grading and 3- and 5-year survival. MATERIAL AND
      METHODS: The study included 22 patients with laryngeal cancer surgical treated in
      ENT Department Medical University of Lodz between 1998 and 1999. The expression
      of MT1-MMP was evaluated immunohistochemically using monoclonal antibodies anti
      MT1-MMP (Mouse Anti-Human MT1-MMP, MAB3319 Chemicon). The polyclonal antibodies
      anti-CK for developing nodal micrometastases was used as well. RESULTS: Positive
      MT1-MMP expression in 68.2% cases was observed. Immunoexpression of MT1-MMP in
      advanced laryngeal carcinoma as indicator for 3-year survival was noted. In
      addition, levels of staining correlated with number of mitoses in tumor front and
      plasmocytolymphatic infiltration in its environment. CONCLUSIONS: The expression
      of MT1-MMP in tumor front appears to play an important role in determining
      prognosis in patients with carcinoma of the larynx.

PMID- 18080693
TI  - [Serum anti-p53 antibodies in gastric cancer patients].
AB  - Mutation of the p53 gene belongs to the most common genetic alteration in human
      cancer. Prognostic significance of serum anti-p53 antibodies in patients with
      gastric cancer is still a matter of controversy. The aim of the study was to
      estimate the presence of anti-p53 antibodies in serum of gastric cancer patients
      and relationship between anti-p53 antibodies and chosen clinical and
      pathomorphological data age, sex, localization of cancer, histology, stage of
      disease, metastases to lymph nodes and the time of survival. MATERIAL AND METHOD:
      Serum samples from 71 patients with gastric cancer were analyzed by specific
      enzyme-linked immunosorbent assay (ELISA) to determine the presence of serum anti
      p53 antibodies. The results were statistically compared with clinical and
      pathological features and postoperative survival. RESULTS: Anti-p53 antibodies
      were detected in 16 (23%) gastric cancer patients. The presence of p53 antibodies
      was connected with intestinal tumor type (p < 0.05) and older age (p = 0.0035).
      There were no association between anti-p53 antibodies, stage and the time of
      survival. CONCLUSION: These results suggest that in gastric cancer patients serum
      anti-p53 antibodies detected by ELISA are not predictor of prognosis.

PMID- 18080694
TI  - [Expression of glutathione S-transferase isoenzymes in tongue and floor of mouth
      squamous cell carcinomas].
AB  - Glutathione S-transferase (GST, EC 2.5.1.18) is one of the most important enzymes
      protecting cells against toxic, electrophilic compounds. It occurs in isoenzymes,
      expression of which changes in various pathological conditions including
      neoplasia. The aim of the present study was to analyze the expression pattern of
      GST pi, mi4 and alpha in human tongue and floor of mouth squamous cell
      carcinomas. MATERIAL AND METHODS: The studies were conducted on tissue samples
      obtained from surgery. RT-PCR was used to determine the GSTs-mRNA expression, and
      Western blotting to study GST pi protein expression. RESULTS: Indicated
      statistically significant differences in GST pi mRNA expression in tumor and
      control tissues. GST pi expression was raised in tumors on both mRNA and protein
      levels, whereas mRNA-GSTmi4 and alfa expression was diverse. CONCLUSION:
      Increased level of GST pi expression indicates its role in carcinogenesis.

PMID- 18080695
TI  - [Short run length of pixels in radiotexture of jaw alveolar ridge in human].
AB  - The real bone structure can be completely described by histomorphometric
      analysis; however, it needs bone biopsy. The development of imaging techniques
      and mathematical methods of texture parameters extraction from radiographs make
      it possible to reveal the characteristic bone features in non-invasive manner.
      The aim of this study was to formulate a mathematical description of image
      texture for finding out whether there exist any structural differences (run
      length matrix) in jaw bone depended on gender. Parameters derived from a run
      length matrix are used to characterize the texture in quantity. MATERIAL AND
      METHODS: 319 digital, standardized, intra-oral, plain radiographs of patients
      qualifying to dental implantations were included into this study. Straight-line
      series (runs) of pixels of similar gray level were searched and analyzed in
      radiographs. RESULTS: Exploring the local bone structure at particular fragments
      of the jaws, in females significantly more frequent the presence of short series
      of pixels in lower alveolar ridge than in upper alveolar ridge are observed. Only
      later aspects of maxillary alveolar ridge have the radiomicroarchitecture
      depending on patient's gender in respect to the investigated feature. In females,
      much more number of short series of the pixels is revealed at lateral aspect of
      alveolar ridge of mandible than at frontal aspect. CONCLUSION: Quantitative
      description of short series of pixels is useful for evaluation of radiotexture in
      images of alveolar ridge.

PMID- 18080696
TI  - [Acute lymphoblastic leukemia in a child with Sturge-Weber syndrome--case
      report].
AB  - Sturge-Weber syndrome belongs to the group of neuroektomesodermal diseases, so
      called facomatoses. In contrast to other diseases of this group, there are not
      any proofs of the genetic determinated background of the syndrome, as well as the
      higher frequency of cancer. However, the higher frequency of benign astrocytomas
      was observed. The presented case of the coincidence of the Sturge-Weber syndrome
      and acute lymphoblastic leukemia is the second case described in the literature.
      The authors present the therapeutical problems, associated with glaucoma and
      epilepsy in the course of this syndrome.

PMID- 18080697
TI  - [Cytokeratin detection as a diagnostic tool in oncology].
AB  - A large part of the cell cytoplasm of the cells consists of components forming
      cytoskeleton. The cytoskeleton is represented by actin-containing microfilaments,
      tubulin-containing microtubules and filaments of intermediate size. The last ones
      have diameters between 7-11 nm. Based on morphological, immunological and
      biochemical criteria the filaments of intermediate size are divided into: a)
      nuclear lamins; b) neurofilaments which are typical for neuronal cells; c)
      vimentin and vimentin-like filaments present especially in mesenchyma derived
      cells and d) filaments containing keratin-like proteins--cytokeratins.
      Cytokeratin filaments are a family of many different polypeptides and are normal
      components of epithelial cell cytoskeleton. Cytokeratins are expressed in various
      types of epithelia in different combinations. This is why antibodies against
      various cytokeratins have been used to characterize a wide variety of epithelial
      tumors. For example immunohistochemical detection of cytokeratin can identify
      micrometastases, not detected by conventional hematoxylin and eosin staining.
      Also serum cytokeratins levels are widely used as the markers of tumors of
      epithelial origin. In this review clinical applications of cytokeratins detection
      are presented.

PMID- 18080698
TI  - [Tuberculosis and HIV infection--main diagnostic and therapeutic problems].
AB  - Tuberculosis pertains to every third HIV-positive person in a world. Therefore
      HIV infection is considered the most evident risk factor for the primary
      tuberculosis or relapse of latent tubercular infection. Pulmonary tuberculosis is
      the most frequent clinical presentation in HIV-positive individuals, although the
      frequency of extrapulmonary tuberculosis is increasing with the CD4+ count
      reduction. Tuberculin skin testing and bacteriological tests are regarded as a
      "gold standard" of diagnosis. Molecular diagnostics and evaluation of a whole
      blood interferon-gamma release assay for the detection of Mycobacterium
      tuberculosis are not cost-effective therefore their application is limited. DOTS
      programs are recommended for the antimycobacterial treatment in HIV-infected
      patients. The increasing drug resistance of Mycobacterium tuberculosis (multi
      drug resistant tuberculosis--MDRTB) is emerging problem in the field of
      tuberculosis management.

PMID- 18080699
TI  - [The new serological markers of rheumatoid arthritis].
AB  - Rheumatoid arthritis (RA) is the most frequent human chronic inflammatory
      autoimmune disease. Its etiology is up to date not known. RA has been proven to
      be an antigen-specific lymphocyte T driven process. Many exo- and endogenous
      antigens having a possible potential to induce and maintain autoimmunologic
      reaction have been described. In this report RA associated autoantibodies,
      especially novel, most specific serological marker--anti-cyclic citrullinated
      peptide antibodies (aCCP) are presented.

PMID- 18080700
TI  - [Apoptosis lymphocytes T and B in adenoid].
AB  - Apoptosis is a physiological form of cell death, which plays an important role in
      embryogenesis, cellular homeostasis, tissue atrophy and removal of tumor and
      mutated cells. Apoptosis of T and B lymphocytes is a fundamental process
      regulating antigen receptor selection during T cell maturation and homeostasis of
      the immune system. It also plays a key role in elimination of autoreactive
      lymphocytes. There are two major signaling pathways of apoptosis: the death
      receptor pathway and intrinsic pathway the mitochondrial pathway.

PMID- 18080701
TI  - [Interactions between ethanol and histamine].
AB  - Histamine is biogenic amine that exerts the numerous important biological
      functions. Alcohol affect histamine action because those have common metabolizing
      enzymes--aldehyde dehydrogenase and aldehyde oxidase. Acetaldehyde can compete
      with aldehydes derived from histamine metabolism. Increased blood acetaldehyde
      resulting from abnormalities of alcohol dehydrogenase genotype in the Orientals
      population can release histamine from mast cells and basophiles, which induces
      the hypersensitivity reactions (flushing). These reactions may be blocked by
      antihistamine drugs. H2-receptor antagonists influence on the ethanol metabolism
      by the inhibition of the activity of alcohol metabolizing enzymes in the stomach
      and liver. Decreased activity of stomach alcohol dehydrogenase results in an
      increase in the blood ethanol concentrations, which may impairs the psychomotor
      skills and exceeds legal limits of driving. There are same evidences that ethanol
      affects the brain histamine level by the changes in the activity of enzymes
      involved in the synthesis and metabolism of histamine.

PMID- 18080702
TI  - [Changes of the localization and function of estrogen receptor alpha in the
      ovaries of postmenopausal women comparing to those of reproductive-age].
AB  - The distribution of estrogen receptors in the ovaries of postmenopausal women is
      a very up-to-date subject in the aspect of advantages and complications of
      estrogen replacement therapy and the risk of estrogen-dependent neoplasms of
      reproductive organs. Both ovarian structure and immunolocalization of estrogen
      receptor alpha (ERalpha) in postmenopausal women are substantially different than
      they are in women at the reproductive-age. The most important changes in the
      ovarian structure after menopause include a blurring of the line between medulla
      and cortex, the reduction of cortex thickness, formation of epithelial inclusion
      cysts, reduction of follicle number, tendency to fragmentation of corpora
      albicantia, and stromal invaginations of the surface epithelium. In the ovaries
      of reproductive-age women, ERalpha is observed in stroma, in protective, granular
      and interstitial cells as well as corpus luteum lutein cells. After menopause it
      is found in the cells of stroma, inclusion cysts and the ovarian surface
      epithelium (OSE). Particularly vital change in the structure of postmenopausal
      women's ovaries in the aspect of the development of estrogen-dependent neoplasms
      is associated with the occurrence of epithelial inclusion cysts and the presence
      of ERalpha in their epithelium. 90% of ovarian epithelial neoplasms, and
      especially serous cancers, are known to develop from epithelial cysts and (or) in
      OSE. On the other hand, finding ERalpha in the ovarian stroma and in luteal and
      paraluteal cells of the corpus luteum, especially in perimenopausal women, proves
      the auto- and (or) paracrine regulation of these cells; it is also an evidence
      for steroidogenic activity in the ovary.

PMID- 18080703
TI  - [Nonoxidative metabolites of ethanol as a markers of recent alcohol drinking].
AB  - Alcoholism is one of the most frequent dependences among people. The early
      detection of alcohol abuse could allow for faster introduction of treatment makes
      essential diagnostic problem. Many biochemical laboratory markers of low
      consumption, abuse or alcohol dependence have been introduced for several last
      years. However, the routinely used laboratory tests require an improvement in the
      diagnostic sensitivity and specificity. Their clinical utility is limited by half
      life in biological fluids. In this paper, the usefulness of nonoxidative
      metabolites of ethanol as a new markers of recent alcohol consumption has been
      presented. They are: fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG),
      ethyl sulphate (EtS) and phosphatidylo ethanol (PEth). The diagnostic value of
      those markers for detection of recent consumption seems to be higher than
      commonly used laboratory tests because the time of detection in biological fluids
      occur between that of the short-term (ethanol, methanol, HTOL/ HIAA index) and
      long-term markers (CDT, GGT MCV), that is, between one day and one week. The
      detection time of ester after the cessation of ethanol intake, so-called time
      window amounts: for FAEEs in serum up to 24 hours, for EtG in urine up to 5 days,
      for EtS in urine one and half day and for PEth in whole blood more than 2 weeks.
      Additionally, because EtG and FAEEs can be detected in hairs for months, they can
      be used as an indicators of chronically harmful alcohol consumption. The
      diagnostic usefulness of nonoxidative metabolites of ethanol has been also
      confirmed in programs of dependences treatment (as an abstinence monitoring
      tests), in forensic (as a postmortem markers for premortem drinking) and in
      prenatal diagnostics (as an indicators of fetal exposure to ethanol).

PMID- 18080704
TI  - Spatial heterogeneity of bacterial populations in monomictic Lake Estanya
      (Huesca, Spain).
AB  - Bacterial population changes were investigated in the monomictic Lake Estanya by
      combining microscopic analysis and two molecular methods involving the
      amplification of 16S rDNA genes using primers for the domain Bacteria and
      subsequent restriction fragment length polymorphism (PCR-RFLP) and denaturing
      gradient gel electrophoresis (PCR-DGGE). Both approaches revealed the vertical
      distribution of predominant microbial morphotypes and phylotypes in both
      holomictic and stratified periods, respectively, and showed that variations in
      structure and composition of bacterial populations are occurring in this lake as
      a function of depth and time. Through principal component analysis (PCA), these
      shifts could be related to different physicochemical parameters with temperature,
      oxygen concentration, and the incident light being of paramount importance as
      structuring variables. Comparison of RFLP and DGGE profiles by scoring
      similarities using the Jaccard coefficient and then building a multidimensional
      scaling map (MDS) showed equivalent results. Both techniques revealed that
      bacterial populations, present in the whole water column in the holomictic
      period, showed a high similarity with those located in the deeper part of the
      lake in the stratified period, evidencing that other factors, both biotic and
      abiotic, should also be considered as a force driving change in the composition
      of the bacterial community. Furthermore, DGGE analysis showed that sequences from
      prominent bands were affiliated to members of four major phyla of the domain
      Bacteria: Cyanobacteria, Bacteroidetes, Proteobacteria, and Actinobacteria, most
      of which corresponded to heterotrophic bacterial populations involved in carbon,
      sulfide, and nitrogen biogeochemical cycles, which were indistinguishable under
      the light microscope.

PMID- 18080705
TI  - Current status of the surgical treatment of atrial fibrillation.
AB  - Atrial fibrillation (AF) affects several million patients worldwide and is
      associated with a number of heart conditions, particularly coronary artery
      disease, rheumatic heart disease, hypertension, and congestive heart failure. The
      treatment of AF and its complications is quite costly. Atrial fibrillation
      usually results from multiple macro-re-entrant circuits in the left atrium. Very
      frequently, particularly in association with mitral valve disease, these circuits
      arise from the area of the junction of the pulmonary venous endothelium and the
      left atrial endocardium. Pharmacological therapy is at best 50% effective.
      Therapeutic options for AF include antiarrhythmic drugs, cardioversion,
      atrioventricular (A-V) node block, pacemaker insertion, and ablative surgery. In
      1987, Cox developed an effective surgical procedure to achieve ablation. Current
      ablative procedures include the classic cut-and-sew Maze operation or a
      modification of it, namely through catheter ablation, namely, cryoablation,
      radiofrequency ablation (dry or irrigated), and other forms of ablation (e.g.,
      laser, microwave). These procedures will be described, along with the
      indications, advantages and disadvantages of each. Special emphasis on the
      alternative means to cutting and sewing to achieve appropriate effective atrial
      scars will be stressed, and our experience with these approaches in 50 patients
      with AF and associated cardiac lesions and their outcomes is presented.

PMID- 18080706
TI  - Parastomal hernia-repair using mesh and an open technique.
AB  - INTRODUCTION: Parastomal hernia occurs in 35%-50% of patients who have had a
      stoma formed, whether for the digestive tract or the urinary tract. There are
      many repair techniques including primary repair and repair using different types
      of mesh prosthesis, and the surgical approach may be open or laparoscopic.
      However, all techniques suffer the disadvantage of a high index of hernia
      recurrence. PATIENTS AND METHODS: This study included 125 patients from the stoma
      clinic at our hospital. Hernia repair was performed on 25 of these patients who
      had a terminal colostomy because of either cancer or inflammatory disease.
      Preoperative colon preparation involved a cathartic, an evacuating enema, and
      antibiotic therapy in the preoperative period. The repair was conducted via an
      anterior approach, dissecting the skin around the stoma in the way a plastic
      surgeon handles an umbilical scar during abdominoplasty, in order to enter the
      hernia site. The hernial sac was left intact to form a bed on which to lay a
      lightweight polypropylene mesh, and this was then fixed to the deep face of the
      aponeurosis all around the stoma, with sutures placed in a U-shape with 1/0 or
      2/0 non-absorbent material. The mesh was also fixed to the external surface of
      the colon with simple sutures of 3/0 polyglycocolic acid. A closed supra
      aponeurotic drain was left in situ, and the skin was closed with 3/0 nylon.
      RESULTS: Of the corpus, 50 patients presented with parastomal hernia (40%), and
      25 of them underwent surgery. These patients were followed for a period of 12
      months, on average (range: 8-24 months). After operation, 2 patients (8%)
      experienced hernia recurrence and underwent further surgery to reinforce the
      abdominal wall with a new insertion of mesh prosthesis; 2 patients (8%) suffered
      surgical wound infection; and 2 patients (8%) developed a seroma. There was no
      rejection of the mesh, erosion of the colon, or fistula formation. CONCLUSIONS:
      Inserting a mesh prosthesis by this technique is a safe effective treatment for
      parastomal hernia, adding another option to the available repair solutions.
      Prospective and comparative studies are required to reinforce this study, and
      they should ideally include a greater number of patients in the study corpus.

PMID- 18080708
TI  - Micovascular techniques have better results in breast reconstruction.

PMID- 18080709
TI  - To drain or not to drain? The role of drainage in the contaminated and infected
      abdomen: an international and personal perspective.

PMID- 18080710
TI  - The need for anticoagulation following inferior vena cava filter placement:
      systematic review.
AB  - PURPOSE: To perform a systemic review to determine the effect of anticoagulation
      on the rates of venous thromboembolism (pulmonary embolus, deep venous
      thrombosis, inferior vena cava (IVC) filter thrombosis) following placement of an
      IVC filter. METHODS: A comprehensive computerized literature search was performed
      to identify relevant articles. Data were abstracted by two reviewers. Studies
      were included if it could be determined whether or not subjects received
      anticoagulation following filter placement, and if follow-up data were presented.
      A meta-analysis of patients from all included studies was performed. A total of
      14 articles were included in the final analysis, but the data from only nine
      articles could be used in the meta-analysis; five studies were excluded because
      they did not present raw data which could be analyzed in the meta-analysis. A
      total of 1,369 subjects were included in the final meta-analysis. RESULTS: The
      summary odds ratio for the effect of anticoagulation on venous thromboembolism
      rates following filter deployment was 0.639 (95% CI 0.351 to 1.159, p = 0.141).
      There was significant heterogeneity in the results from different studies [Q
      statistic of 15.95 (p = 0.043)]. Following the meta-analysis, there was a trend
      toward decreased venous thromboembolism rates in patients with post-filter
      anticoagulation (12.3% vs. 15.8%), but the result failed to reach statistical
      significance. CONCLUSION: Inferior vena cava filters can be placed in patients
      who cannot receive concomitant anticoagulation without placing them at
      significantly higher risk of development of venous thromboembolism.

PMID- 18080711
TI  - The cough reflex in animals: relevance to human cough research.
AB  - All mammalian species studied cough or display some similar respiratory reflex
      upon aerosol challenge with tussigenic stimuli such as citric acid or capsaicin.
      Animals cough to the same stimuli that evoke coughing in humans, and therapeutic
      agents that display antitussive effects in human studies also prevent coughing in
      animals. The many invasive procedures and complementary in vitro studies possible
      in animals but not readily reproduced in human subjects, along with the proven
      predictive value of cough studies in animals, provide the rationale for animal
      modeling of human cough. The advantages and disadvantages of studying cough in
      animals are discussed.

PMID- 18080712
TI  - Hiatal hernia repair at the initial laparoscopic adjustable gastric band
      operation reduces the need for reoperation.
AB  - BACKGROUND: Intractable reflux, either due to gastric prolapse or concentric
      pouch dilatation has been the most common indication for reoperation or band
      removal after laparoscopic adjustable gastric banding (LAGB). We have previously
      found that a simple hiatal hernia repair (HHR) leads to remission of these
      symptoms minimizing the need for band removal. We have subsequently added crural
      repair/HHR at the initial operation, where indicated. In this study compare the
      rate of reoperation in patients who underwent LAGB alone, or with concurrent HHR.
      METHODS: A retrospective review of a prospective database of all patients
      undergoing LAGB was performed to determine the incidence of reoperation in the
      two groups. RESULTS: Between July 2001 and August of 2006, 1298 patients
      underwent LAGB and 520 patients underwent LAGB with concurrent HHR (LAGB/HHR).
      The mean initial weight and BMI were 128 kg (range, 71.1-245.7 kg) and 45.4
      kg/m(2) (range, 28-75 kg/m(2)). Average follow-up for the LAGB and LAGB/HHR
      groups was 24.8 and 20.5 months, respectively. Rate of reoperation for HHR alone,
      or with band slip or concentric pouch dilatation, for LAGB and LAGB/HHR groups
      was 5.6% and 1.7% respectively (p < 0.001). Total reoperation rate for slip, HHR
      and pouch dilatation was 7.9% and 3.5%, respectively (p < 0.001). There was no
      significant difference in rate of slip repair alone between the two groups: 2.3%
      and 1.7%, respectively (p < 0.44). CONCLUSIONS: Adding HHR to LAGB where
      indicated significantly reduces reoperation rate. Every effort should be made to
      detect and repair HHR during placement of the band, as it will decrease future
      need for reoperation.

PMID- 18080713
TI  - Clinical, manometric, and ultrasonographic results of pneumatic balloon
      dilatation vs. lateral internal sphincterotomy for chronic anal fissure: a
      prospective, randomized, controlled trial.
AB  - PURPOSE: This prospective, randomized, controlled trial was designed to compare
      the clinical, functional, and morphologic results of pneumatic balloon dilatation
      with lateral internal sphincterotomy for the treatment of chronic anal fissure.
      METHODS: All patients with symptomatic chronic anal fissure were randomly
      assigned to pneumatic balloon dilatation or lateral internal sphincterotomy and
      invited to complete a standardized questionnaire inquiring about their symptoms.
      Anal ultrasonography and anal manometry were performed before and six months
      after surgery. A proctologic examination was performed between the fifth and
      sixth postoperative weeks. Anal continence, scored by using a validated
      continence grading scale, was evaluated preoperatively at 1 and 6 weeks and at 12
      and 24 months. RESULTS: Fifty-three patients, who satisfied selection criteria,
      were enrolled in the trial. Four patients (7.5 percent) were lost to follow-up.
      Twenty-four patients (11 males; mean age, 42 +/- 8.2 years) underwent pneumatic
      balloon dilatation and 25 patients (10 males; mean age, 44 +/- 7.3 years)
      underwent lateral internal sphincterotomy. Fissure-healing rates were 83.3
      percent in the pneumatic balloon dilatation and 92 percent in the lateral
      internal sphincterotomy group. Recurrent anal fissure was observed in one patient
      (4 percent) after lateral internal sphincterotomy. At anal manometry, mean
      resting pressure decrements obtained after pneumatic balloon dilatation and
      lateral internal sphincterotomy were 30.5 and 34.3 percent, respectively. After
      pneumatic balloon dilatation, anal ultrasonography did not show any significant
      sphincter damage. At 24-month follow-up, the incidence of incontinence,
      irrespective of severity, was 0 percent in the pneumatic balloon dilatation group
      and 16 percent in the lateral internal sphincterotomy group (P < 0.0001).
      CONCLUSIONS: As lateral internal sphincterotomy, pneumatic balloon dilatation
      grants a high anal fissure-healing rate but with a statistically significant
      reduction in postoperative anal incontinence.

PMID- 18080714
TI  - Use of intracolonic bypass secured by a biodegradable anastomotic ring to protect
      the low rectal anastomosis.
AB  - PURPOSE: Because of the relatively high morbidity and mortality of anastomotic
      leakage in patients with low rectal cancer who receive an anterior resection,
      many fecal diverting methods have been introduced. This study was designed to
      assess the efficacy and safety of the Valtrac-secured intracolonic bypass in
      protecting low rectal anastomosis and to compare the efficacy and complications
      of Valtrac-secured intracolonic bypass with those of loop ileostomy. METHODS:
      From January 2002 to April 2006, 83 patients with rectal cancer who underwent
      elective low anterior resection received intracolonic bypass or ileostomy.
      Demographics, clinical features, and operative data were recorded. RESULTS: Forty
      four patients (53 percent) received a Valtrac-secured intracolonic bypass and 39
      patients (47 percent) a loop ileostomy. The demographics and clinical features of
      the groups were similar. None of the patients developed clinical anastomotic
      leakage. Longer overall postoperative hospital stay (21.3 +/- 5.8 days) and
      higher costs incurred (3.1 +/- 0.9 x $1,000 U.S. dollars) were observed in the
      ileostomy group than in the intracolonic bypass group (12.5 +/- 6.3 days, 4.4 +/-
      1.2 x $1,000 U.S. dollars; P < 0.05). Stoma-related complications in the
      ileostomy group included dermatitis (12.8 percent), bleeding (2.6 percent), and
      intestinal obstruction after stoma closure (5.1 percent). No complications were
      observed in the intracolonic bypass group except for the Valtrac ring discharging
      en bloc, which compromised fecal evacuation in two cases (4.5 percent).
      CONCLUSIONS: The Valtrac-secured intracolonic bypass procedure is a safe,
      effective, but time-limited, diverting technique to protect an elective low
      colorectal anastomosis. Valtrac-secured intracolonic bypass, in contrast to loop
      ileostomy, avoids stoma-related complications or readmission for closure and is
      associated with decreased hospital time and cost.

PMID- 18080715
TI  - Production and bioactivity of common lichen metabolites as exemplified by
      Heterodea muelleri (Hampe) Nyl.
AB  - Based on results of a former study in 2005, this investigation aimed at
      quantifying UV- and cold temperature stress-induced changes within the secondary
      metabolite production of the cultured mycobiont of the lichen Heterodea muelleri
      (Hampe) Nyl. The chemical profiles of the mycobiont cultures and the lichen
      thallus were determined by high-performance liquid chromatography (HPLC) and thin
      layer chromatography (TLC) analyses. The voucher specimen of H. muelleri produced
      diffractaic acid as a major polyketide and barbatic acid as a satellite compound,
      whereas the untreated mycobiont did not contain any detectable secondary
      metabolites. While UV-C stress caused a general increase in substance formation,
      cold temperature stress resulted in a strong activation of barbatic acid
      biosynthesis. A further series of experiments focused on the effect of
      diffractaic and barbatic acids on the growth of the symbiotic photobiont
      Trebouxia jamesii; usnic acid was similarly tested. Pure substances were obtained
      from mycobiont cultures by performing preparative TLC. A determined quantity of
      algae was incubated on BBM plates that contained three different concentrations
      of the pure lichen metabolites. The growth of the photobionts was monitored over
      a period of 1 mo to evaluate the impact of each substance on the cultured algae.
      While diffractaic and usnic acid had no noticeable effect, barbatic acid strongly
      inhibited algal growth and resulted in cell death.

PMID- 18080716
TI  - A novel function of the receptor for advanced glycation end-products (RAGE) in
      association with tumorigenesis and tumor differentiation of HCC.
AB  - BACKGROUND: The expression of the receptor for advanced glycation end products
      (RAGE) has an impact on the mechanisms giving rise to characteristic features of
      various cancer cells. The purpose of this study was to elucidate the
      clinicopathological relevance of the level of RAGE expression in patients with
      hepatocellular carcinoma (HCC) and to explore the effect of RAGE expression on
      the characteristic features of HCC. METHODS: The expression of RAGE was assessed
      in paired cancer and noncancerous tissues with HCC, using reverse-transcription
      polymerase chain reaction (RT-PCR), and immunohistochemistry. The quantitative RT
      PCR data were analyzed in association with the clinicopathological factors of the
      patients with HCC. In in vitro experiments, the survival of RAGE-transfected Cos7
      and mock-transfected Cos7 cells was compared under hypoxic conditions. In
      addition, after reducing RAGE levels in RAGE-transfected Cos7 cells by siRNA,
      similar experiments were performed. RESULTS: The expression of RAGE mRNA was
      lower in normal liver than in hepatitis and highest in HCC. Furthermore, in HCC,
      it was high in well- and moderately differentiated tumors but declined as tumors
      dedifferentiated to poorly differentiated HCC. Furthermore, HCC lines resistant
      to hypoxia were found to have higher levels of RAGE expression, and RAGE
      transfectant also showed significantly prolonged survival under hypoxia.
      CONCLUSIONS: Our results suggest that HCC during the early stage of tumorigenesis
      with less blood supply may acquire resistance to stringent hypoxic milieu by
      hypoxia-induced RAGE expression.

PMID- 18080717
TI  - The complex relationships between sentinel node positivity, patient age, and
      primary tumor desmoplasia: analysis of 2303 melanoma patients treated at a single
      center.
AB  - BACKGROUND: Recent studies have shown that younger age is associated with a
      greater likelihood of positive sentinel node (SN) status in patients with
      localized melanoma. This is a paradoxical situation because it is well known that
      younger patients have a far more favorable overall survival rate than older
      patients. In addition, desmoplastic melanomas are associated with a lower
      frequency of SN positivity, although this is less well documented. METHODS: The
      outcome for 2303 cutaneous melanoma patients undergoing sentinel lymph node
      biopsy (SLNB) at the Sydney Melanoma Unit between 1993 and 2006 was examined to
      clarify the role of patient age and desmoplastic histogenetic type on SN
      positivity. RESULTS: By univariate analysis, patients aged <40 years had a higher
      SN positivity rate (22.6%) than patients aged > or =40 years (15.4%; P < .004).
      Features associated with SN positivity were tumor thickness, mitotic rate,
      ulcerative state, and nondesmoplastic histogenetic type (all P < .001). Patient
      sex and primary melanoma site were not statistically significantly associated.
      Multivariate analyses revealed that only tumor thickness, patient age,
      nondesmoplastic type (all P < .001), and ulceration (P < .026) were independently
      associated with SN positivity. Key prognostic determinants such as total number
      of disease-positive nodes (both SNs and non-SNs) and site of first relapse did
      not vary according to age. CONCLUSIONS: Tumor thickness, patient age,
      desmoplastic histogenetic type, and primary melanoma ulceration were all
      independently associated with SN status. The factors underlying the paradox of a
      poorer survival rate in older patients despite a lower incidence of positive SNs
      remain unclear.

PMID- 18080718
TI  - Prognosis of patients who relapse after fertility-sparing surgery in epithelial
      ovarian cancer.
AB  - BACKGROUND: The prognosis for patients who develop a recurrence after fertility
      sparing surgery for epithelial ovarian cancer (EOC) remains unclear. This is the
      first study to evaluate survival in patients who have developed a recurrence in
      this context. METHODS: The outcomes of relapsed patients reported in the
      literature in the four main series of fertility-sparing surgery for EOC were
      reviewed and updated (where feasible). RESULTS: Twenty-three of the 166 patients
      in the series were reported to have recurrent disease. The site of the recurrence
      was the peritoneum (+/- remaining ovary) in 17 patients, and distant in six
      patients. Twelve patients died of recurrent disease, two are still alive with
      persistent disease, eight are disease-free, and one is alive but her exact status
      is not known. Among eight patients (34%) with an isolated recurrence on the
      remaining ovary, two died and one was lost to follow-up. CONCLUSION: In this
      carefully monitored population, including systematic radiological examinations,
      the rate of isolated recurrences on the spared ovary is low. Recurrence in these
      patients carries a poor prognosis. Such results suggest that initial selection of
      candidates for fertility-sparing surgery should be carefully defined to reduce
      the rate of recurrences that carry a poor prognosis.

PMID- 18080719
TI  - Why Oregon patients request assisted death: family members' views.
AB  - BACKGROUND: Physician assisted death (PAD) was legalized through Oregon's Death
      with Dignity Act in 1994 and enacted in 1997. OBJECTIVE: The objective of this
      paper was to learn from family members why their loved ones requested PAD.
      DESIGN: This study used the cross-sectional survey. PARTICIPANTS: Participants of
      this study included family members of 83 Oregon decedents who made explicit
      requests for legalized PAD before their deaths, including 52 decedents who
      received prescriptions for a lethal medication and 32 who died of PAD.
      MEASUREMENTS: Family members rated the importance of 28 possible reasons their
      loved ones requested PAD on a 1-5 Likert scale, with higher scores representing
      greater importance. RESULTS: According to family members, the most important
      reasons that their loved ones requested PAD, all with a median score of 4.5 or
      greater, were wanting to control the circumstances of death and die at home, and
      worries about loss of dignity and future losses of independence, quality of life,
      and self-care ability. No physical symptoms at the time of the request were rated
      higher than a median of 2 in importance. Worries about symptoms and experiences
      in the future were, in general, more important reasons than symptoms or
      experiences at the time of the request. According to family members, the least
      important reasons their loved ones requested PAD included depression, financial
      concerns, and poor social support. CONCLUSIONS: Interventions that help patients
      maintain control, independence, and self-care in a home environment may be
      effective means of addressing serious requests for PAD.

PMID- 18080720
TI  - Foramen magnum meningioma: Dysphagia of atypical etiology.
AB  - INTRODUCTION: We present a case of a foramen magnum meningioma that highlights
      the importance of the neurologic exam when evaluating a patient with dysphagia. A
      58-year-old woman presented with an 18-month history of progressive dysphagia,
      chronic cough and 30-pound weight loss. Prior gastroenterologic and laryngologic
      workup was unrevealing. RESULTS: Her neurologic examination revealed an absent
      gag reflex, decreased sensation to light touch on bilateral distal extremities,
      hyperreflexia, and tandem gait instability. Repeat esophagogastroduodenoscopy was
      normal, whereas laryngoscopy and video fluoroscopy revealed marked hypopharyngeal
      dysfunction. Brain magnetic resonance imaging demonstrated a 3.1 x 2.7 x 2.9 cm
      foramen magnum mass consistent with meningioma. The patient underwent
      neurosurgical resection of her mass with near complete resolution of her
      neurologic symptoms. Pathology confirmed diagnosis of a WHO grade I
      meningothelial meningioma. CONCLUSION: CNS pathology is an uncommon but
      impressive cause of dysphagia. Our case demonstrates the importance of a thorough
      neurologic survey when evaluating such a patient.

PMID- 18080721
TI  - Enterohormonal changes after digestive adaptation: five-year results of a
      surgical proposal to treat obesity and associated diseases.
AB  - BACKGROUND: Recent physiological knowledge allows the design of bariatric
      procedures that aim at neuroendocrine changes instead of at restriction and
      malabsorption. Digestive adaptation is a surgical technique for obesity based in
      this rationale. METHODS: The technique includes a sleeve gastrectomy, an
      omentectomy and a jejunectomy that leaves initial jejunum and small bowel
      totaling at least 3 m (still within normal variation of adult human bowel
      length). Fasting ghrelin and resistin and fasting and postprandial GLP-1 and PYY
      were measured pre- and postoperatively. RESULTS:  PATIENTS: 228 patients with
      initial body mass index (BMI) varying from 35 to 51 kg/m(2); follow-up: 1 to 5
      years; average EBMIL% was 79.7% in the first year; 77.7% in the second year;
      71.6% in the third year; 68.9% in the fourth year. PATIENTS present early satiety
      and major improvement in presurgical comorbidities, especially diabetes. Fasting
      ghrelin and resistin were significantly reduced (P < 0.05); GLP-1 and PYY
      response to food ingestion was enhanced (P < 0.05). Surgical complications (4.4%)
      were resolved without sequela and without mortality. There was neither diarrhea
      nor detected malabsorption. CONCLUSIONS: Based on physiological and supported by
      evolutionary data, this procedure creates a proportionally reduced
      gastrointestinal (GI) tract that amplifies postprandial neuroendocrine responses.
      It leaves basic GI functions unharmed. It reduces production of ghrelin and
      resistin and takes more nutrients to be absorbed distally enhancing GLP-1 and PYY
      secretion. Diabetes was improved significantly without duodenal exclusion. The
      patients do not present symptoms nor need nutritional support or drug medication
      because of the procedure, which is safe to perform.

PMID- 18080722
TI  - Weight loss and body composition during the first postoperative year of a
      laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: Weight loss in patients undergoing gastric bypass should be primarily
      from fat mass (FM), minimizing the fat-free mass (FFM) loss. The aim of this
      study was to analyze changes in body weight and body composition during the first
      postoperative year in 50 morbidly obese patients undergoing a Laparoscopic Roux
      en-Y gastric bypass (LRYGBP) at the Obesity Clinic of the ABC Medical Center.
      METHODS: Patient's weight and body composition were obtained before surgery and 1
      year later using bioelectrical impedance analysis (BIA). Weight, FM, FMM, and
      total body water (TBW) were measured before and 1 year after surgery. Changes in
      body composition were particularly analyzed. RESULTS: There were 29 females and
      21 males with mean age of 41 +/- 12 years. Mean BMI before surgery and 1 year
      after surgery was 44.4 +/- 7.4 kg/m(2) and 28.3+/-4.3 kg/m(2), respectively. The
      percentage of excess body weight loss at the 1-year period was 86% for women and
      79.6% for men. The percentage of FM before surgery was 47.7 +/- 5.1, and 1 year
      later it was 28.8 +/- 8. The percentage of FFM was 66.5 +/- 16.5 before surgery
      and 58.3 +/- 13 at 1 year. CONCLUSIONS: There is a significant weight loss in
      patients undergoing LRYGBP. Weight loss mainly occurs as a consequence of
      reduction in the FM with less impact on the FFM.

PMID- 18080723
TI  - Psychosocial functioning, personality, and body image following vertical banded
      gastroplasty.
AB  - BACKGROUND: In addition to increased risks of morbidity and mortality, extreme
      obesity is substantially associated with psychosocial problems. Therefore, the
      ultimate goal of bariatric surgery should not only be reducing weight and
      counteracting comorbid conditions but also improving psychosocial functioning. In
      addition to being an important goal of bariatric surgery, enhanced psychosocial
      functioning may motivate patients to adhere to adequate health behavior to
      maintain the surgically established weight loss. METHODS: We evaluated early
      postoperative psychosocial functioning in several domains over time.
      Preoperatively as well as 6, 12, and 24 months after vertical banded
      gastroplasty, 104 patients were psychologically assessed using a semi-structured
      interview and psychological questionnaires focusing on psychosocial functioning,
      personality, and body image. RESULTS: Over time, we found significant changes in
      weight: 2 years excess weight loss was 58.6%. In addition, most aspects of
      psychosocial functioning showed significant improvements over time. However,
      initial improvements in depressive symptoms, sleeping problems, and neuroticism
      did not last. With respect to personality features, only short-term changes in
      self-esteem were found. The most robust improvements were seen in the case of
      body image. Finally, within the patient group, there was a wide variability in
      changes. CONCLUSION: Vertical banded gastroplasty not only leads to considerable
      weight loss but also to significant improvements in psychosocial functioning.
      However, some improvements waned over time, and successful postoperative
      functioning did not apply to all patients.

PMID- 18080724
TI  - The serial changes of ghrelin and leptin levels and their relations to weight
      loss after laparoscopic minigastric bypass surgery.
AB  - BACKGROUND: The ghrelin and leptin levels have been reported to be correlated
      with weight loss after bariatric surgery. However, the serial changes of ghrelin
      and leptin levels after laparoscopic minigastric bypass surgery (LMGBP) have not
      been reported yet. Therefore, we aimed to evaluate their serial changes and to
      analyze their relations to weight reduction after LMGBP. METHODS: Serial fasting
      serum leptin and ghrelin concentrations were measured in 68 morbidly obese
      patients before (M0) and 1 (M1), 3 (M3), 6 (M6), and 12 (M12) months after LMGBP
      surgery. The correlations between ghrelin, insulin, and leptin concentrations and
      weight reduction were analyzed. RESULTS: Leptin levels were significantly reduced
      at 1, 3, 6, and 12 months after surgery, respectively (vs M0, p < 0.001), whereas
      the ghrelin concentrations were not significantly changed after surgery. The
      percent of excess BMI lost (%EBL) 12 months after surgery was negatively
      correlated with higher preoperative ghrelin concentrations (p = 0.004) and larger
      preoperative BMI (p = 0.002) in the multivariate analysis. CONCLUSION: Higher
      preoperative ghrelin concentrations and larger BMI are predictive of less %EBL at
      12 months after LMGBP surgery.

PMID- 18080725
TI  - Pressure-controlled ventilation does not improve gas exchange in morbidly obese
      patients undergoing abdominal surgery.
AB  - BACKGROUND: Morbid obesity results in marked respiratory pathophysiologic changes
      that may lead to impaired intraoperative gas exchange. The decelerating
      inspiratory flow and constant inspiratory airway pressure resulting from pressure
      controlled ventilation (PCV) may be more adapted to these changes and improve gas
      exchanges compared with volume-controlled ventilation (VCV). METHODS: Forty
      morbidly obese patients scheduled for gastric bypass were included in this study.
      Total intravenous anesthesia was given using the target-controlled infusion
      technique. During the first intraoperative hour, VCV was used and the tidal
      volume was adjusted to keep end-tidal PCO(2) around 35 mmHg. After 1 h, patients
      were randomly allocated to 30-min VCV followed by 30-min PCV or the opposite
      sequence using a Siemens Servo 300. FiO(2) was 0.6. During PCV, airway pressure
      was adjusted to provide the same tidal volume as during VCV. Arterial blood was
      sampled for gas analysis every 15 min. Ventilatory parameters were also recorded.
      RESULTS: Peak inspiratory airway pressures were significantly lower during PCV
      than during VCV (P < 0.0001). The other ventilatory parameters were similar
      during the two periods of ventilation. PaO(2) and PaCO(2) were not significantly
      different during PCV and VCV. CONCLUSION: PCV does not improve gas exchange in
      morbidly obese patients undergoing gastric bypass compared to VCV.

PMID- 18080726
TI  - The impact of race on weight loss after Roux-en-Y gastric bypass surgery.
AB  - BACKGROUND: Gastric bypass surgery for morbid obesity has dramatically increased
      in volume over the past decade. Caucasian patients have been noted previously to
      lose more weight after bariatric surgery than African-Americans patients. Data
      regarding predictors of maintaining weight loss after surgery are minimal. We
      sought to determine predictors of long-term weight loss after bariatric surgery.
      METHODS: Retrospective analysis using a multivariate logistic regression model of
      all patients undergoing Roux-en-Y gastric bypass surgery at the Medical
      University of South Carolina from May 1993 to December 2004 for whom 2 years of
      follow-up data was available. Our dependent variable was the percentage of weight
      lost from baseline, dichotomized at +/-35%. Our primary independent variable was
      race, defined as Caucasian, African-American, or other. Relevant covariates were
      added to the model to control for their potential effects on outcome. RESULTS:
      One hundred eleven patients (17 male/94 female; 85% Caucasian, mean age 44 years
      (range 18-68 years). In our model, Caucasian subjects (adjusted odds ratio [OR] =
      7.60, 95% confidence intervals [95%CI] = 1.83-31.5) and late post surgical
      complications (adjusted OR = 2.67, 95%CI = 1.05-6.80) significantly predicted
      weight loss at 2 years, after controlling for relevant confounders. Other
      covariates did not significantly impact the model. CONCLUSION: Race and late post
      surgical complications significantly impacted the percentage of weight loss at 2
      years for patients undergoing Roux-en-Y gastric bypass surgery at our
      institution. Future research should be directed at determining potential genetic
      and/or social reasons for these differences.

PMID- 18080727
TI  - Incidence of lower limbs deep vein thrombosis after open and laparoscopic gastric
      bypass: a prospective study.
AB  - BACKGROUND: Lower limbs deep vein thrombosis (DVT) and pulmonary embolism (PE)
      are major causes of morbidity and mortality and are even higher in bariatric
      patients. The longer operative time and higher immobility in these patients
      increase the DVT risk. Although deaths after bariatric surgery have been
      reported, there is no consensus regarding the prophylaxis of DVT. This study's
      objective is to determine the incidence of lower limbs DVT in patients submitted
      to Roux-en-Y-gastric bypass (RYGBP) under prophylaxis by enoxaparin. METHODS:
      Patients with body mass index (BMI) equal to or higher than 35 kg/m(2) who
      submitted to RYGBP by laparotomy or laparoscopy using 40 mg/day of enoxaparin for
      15 days were recruited between October 2004 and August 2005. Individuals with
      previous DVT and heparin allergy were excluded. Patients were tested for DVT
      using color Doppler ultrasound performed before surgery and on the second and
      fifth weeks after surgery. RESULTS: The study population included 136 patients,
      with 126 concluding the protocol. There were 79% (100/126) of female patients
      aged 19 to 65 years old, with mean of 40 years SD = 10 and BMI between 35 and 61
      kg/m(2), mean of 43 kg/m(2) (SD = 5). All patients who submitted to RYGBP were
      divided as 55% (69/126) by laparoscopy and 45% (57/126) by laparotomy. The
      incidence rate of lower limbs DVT was 0.79% (1/126). CONCLUSION: The low
      incidence rate of DVT found in our study suggests that obesity might not be a
      major risk factor for venous thromboembolism in patients submitted to RYGBP.

PMID- 18080728
TI  - Laparoscopic conversion of vertical banded gastroplasty (Mason MacLean) into Roux
      en-Y gastric bypass.
AB  - BACKGROUND: Revision of bariatric procedures is required in 10 to 25% of patients
      either for insufficient weight loss or for complications. Patients undergoing
      vertical banded gastroplasty (VBG; Mason MacLean) may require revision in up to
      half of the cases in the long term. Roux-en-Y gastric bypass (RYGBP) is
      considered the procedure of choice for revision of VBG gastroplasty. PATIENTS AND
      METHODS: Eighteen patients, 16 women and 2 men with a mean age of 41.7 years
      (range 27-72) and a mean BMI at 37.6 kg/m(2) (range 22.5-47), underwent
      laparoscopic conversion of VBG into RYGBP. Indications for revisional surgery
      were insufficient weight loss (11 patients), stoma stenosis (4 patients), and
      acid reflux (3 patients). RESULTS: Operative time was on average 203 min (range
      60-300 min), and conversion was required in one patient (5.5%). There was no
      early postoperative mortality, and four patients (22.2%) developed immediate
      postoperative complications (gastrojejunostomy leak 1; stenosis of the
      gastrojejunal anastomosis 2; liver abscess 1). One patient died 6 months after
      conversion because of a bleeding anastomotic ulcer (late mortality 5.5%). Two
      patients (11.5%) developed late complications (incisional hernia 1; internal
      hernia 1). At a mean follow-up of 23, 4 months BMI is on average 29.8 kg/m(2)
      (range 22.7-37). CONCLUSION: Although revision of failed VBG into RYGBP gives
      good functional results, the risk of postoperative serious complications must be
      carefully evaluated before revision.

PMID- 18080729
TI  - Psychosocial impact of abdominoplasty.
AB  - BACKGROUND: The number of patients desiring reconstructive surgery after a huge
      weight loss achieved with gastric banding is increasing. This study was
      undertaken to determine whether plastic surgical removal of an overlap flap has a
      psychosocial effect on patients. METHODS: Thirty-women and four men who underwent
      overlap flap surgery were interviewed 1 day before, and again 3 and approximately
      12 months after the procedure using a series of instruments: Strauss and Appelt's
      Questionnaire for assessing one's body, the Body Perception Questionnaire by
      Paulus, the questionnaire for satisfaction of life by Fahrenberg, Myrtek,
      Schumacher, and Brahler, the Hospital Anxiety and Depression Scale (German
      version) by Herrmann, Buss, and Snaith, and the authors' general questionnaire
      after surgery. The same clinical parameters were also investigated in a control
      group of persons who did not undergo plastic surgery. Comparisons were made
      before and after surgery between and in both groups. RESULTS: In contrast to the
      control group, surgical patients reported a highly significant increase in self
      confidence and the feeling of being attractive (p <or= 0.001); 75% of the
      surgical patients stated that their expectations were met by the plastic surgical
      intervention. CONCLUSION: Plastic surgery after weight loss improves body image
      and subjective quality of life. These results will influence the indication for a
      reconstructive operation in future.

PMID- 18080730
TI  - Investigation of drug delivery by iontophoresis in a surgical wound utilizing
      microdialysis.
AB  - PURPOSE: This study investigated the penetration of lidocaine around and through
      a sutured incision following the application of iontophoretic and passive patches
      in the CD Hairless rat. MATERIALS AND METHODS: Concentrations in localized areas
      (suture, dermis, subcutaneous, and vascular) were determined using microdialysis
      sampling followed by analysis using liquid chromatography with UV detection.
      RESULTS: Iontophoresis significantly enhanced the dermal penetration of
      lidocaine. In an intact skin model, dermal concentrations were 40 times greater
      following iontophoretic delivery compared to passive delivery. In a sutured
      incision model, iontophoresis enhanced localized concentrations in the dermis,
      suture, and subcutaneous regions by 6-, 15-, and 20-fold, respectively.
      Iontophoretic delivery to a region containing a sutured incision was focused to
      the incision resulting in a greater increase in the suture concentration and in
      the subcutaneous region directly below the incision. CONCLUSIONS: The four
      microdialysis probe design was successful in the determination of localized drug
      penetration in a sutured incision model. Iontophoresis enhanced skin penetration
      and allowed for site specific delivery when applied to a sutured incision.

PMID- 18080731
TI  - Simultaneous determination of cadmium (II) and zinc (II) by molecular
      fluorescence spectroscopy and multiple linear regression using an
      anthrylpentaazamacrocycle chemosensor.
AB  - The work that is reported here concerns a method that allows the simultaneous
      determination of cadmium (II) and zinc (II) in aqueous solution by molecular
      fluorescence spectroscopy using 9-(1',4',7',10',13'-pentaazacyclopentadecyl)
      methylanthracene. For this chemosensor, the fluorophore pi-system is insulated
      from an azacrown donor by one methylene group. A self-quenching mechanism,
      resulting from an electron transfer from the nitrogens of the azacrown to the
      excited aromatic system, essentially precludes fluorescence emission.
      Fluorescence is restored when cadmium (II) or zinc (II) are chelated by the
      macrocycle. The difference between the emission spectra profiles of the free
      chemosensor, the cadmium and the zinc chelates is such that the concentration
      determination of the two metals and the remaining free chemosensor is possible at
      the nanomolar scale in only one experiment using a multiple linear regression
      algorithm. Usefulness and convenience of this simple method is proven by steady
      state and kinetic quantitative determination experiments.

PMID- 18080732
TI  - Phenotype-genotype analysis of cryopyrin-associated periodic syndromes (CAPS):
      description of a rare non-exon 3 and a novel CIAS1 missense mutation.
AB  - We describe in this paper the phenotype-genotype analysis of a Brazilian cohort
      of patients with cryopyrin-associated periodic syndromes (CAPS). Patient 1
      presented with an urticarial rash and recurrent fever exacerbated by cold
      weather, arthritis, and anterior uveitis, thus, receiving a clinical diagnosis of
      familial cold autoinflammatory syndrome. CIAS1 sequencing identified the T436I
      mutation, previously associated to a clinical phenotype of chronic infantile
      neurological cutaneous and articular/neonatal onset multisystem inflammatory
      disease. Patient 2 developed a papular exanthema with daily fever shortly after
      birth, frontal bossing, patellae enlargement, and cognitive and motor
      impairments. Sequencing identified the exceedingly rare G755R CIAS1 mutation in
      exon 4. Patient 3 developed skin rash and articular symptoms 6 h after birth,
      followed by aseptic meningitis. He was found to have the novel C148Y missense
      mutation in CIAS1. This report expands the spectrum of CIAS1 mutations associated
      to clinical disease, suggests that the same mutation can be associated with
      different clinical syndromes, and supports the evidence that CAPS patients should
      always be screened for mutations outside exon 3.

PMID- 18080733
TI  - Relation of antisocial and psychopathic traits to suicide-related behavior among
      offenders.
AB  - Offenders with antisocial traits are relatively likely to attempt suicide,
      largely because they are more likely to have high negative emotionality and low
      constraint. Among 682 male offenders, we tested whether negative emotionality,
      low constraint, and also substance use problems mediated any relationship between
      antisocial personality disorder (ASPD) and psychopathy on the one hand, and
      suicide-related behavior (SRB) and ideation on the other. ASPD and the
      impulsivity/lifestyle features of psychopathy weakly predicted SRB. High negative
      emotionality and low constraint (but not substance use) mediated the relation
      between ASPD and SRB. Impulsivity/lifestyle features of psychopathy retained an
      independent predictive effect. Self-report psychopathy measures added unique
      predictive variance to the Psychopathy Checklist-Revised. We discuss implications
      for suicide risk assessment and prevention.

PMID- 18080734
TI  - Introduction to commentaries on the Illinois pilot study of lineup reforms.

PMID- 18080735
TI  - Prenatal sex hormones (maternal and amniotic fluid) and gender-related play
      behavior in 13-month-old Infants.
AB  - Testosterone, estradiol, and progesterone levels were measured in the second
      trimester of pregnancy in maternal serum and amniotic fluid, and related to
      direct observations of gender-related play behavior in 63 male and 63 female
      offspring at age 13 months. During a structured play session, sex differences in
      toy preference were found: boys played more with masculine toys than girls (d =
      .53) and girls played more with feminine toys than boys (d = .35). Normal within
      sex variation in prenatal testosterone and estradiol levels was not significantly
      related to preference for masculine or feminine toys. For progesterone, an
      unexpected significant positive relationship was found in boys between the level
      in amniotic fluid and masculine toy preference. The mechanism explaining this
      relationship is presently not clear, and the finding may be a spurious one. The
      results of this study may indicate that a hormonal basis for the development of
      sex-typed toy preferences may manifest itself only after toddlerhood. It may also
      be that the effect size of this relationship is so small that it should be
      investigated with more sensitive measures or in larger populations.

PMID- 18080736
TI  - Intrauterine position effects on anogenital distance and digit ratio in male and
      female mice.
AB  - Anogenital distance (AGD) and the ratio of the second (index) to fourth (ring)
      digit lengths (2D:4D) are two widely used indicators of prenatal androgen
      exposure. The former is commonly used in rodent models, while the latter is
      principally used in human studies. We investigated variation in these two traits
      in C57BL/6J mice to test the hypothesis that variation in these two traits
      reflect a common underlying variable, presumably testosterone exposure. AGD is a
      sexually dimorphic trait used to sex young rodents. This distance typically
      increases and becomes more male-like in female pups when their uterine neighbors
      are male. 2D:4D is sexually dimorphic in a number of species, including humans
      and other great apes. Lower digit ratios may be associated with greater exposure
      to androgens during fetal development in humans. We found the expected sexual
      dimorphism in AGD, but no significant sex difference in 2D:4D, and no correlation
      between 2D:4D and AGD. Gestating next to males increased a pup's 2D:4D ratio, but
      it had no effect on AGD. The lack of correlation between 2D:4D and AGDs in this
      mouse strain suggests that these two measures do not reflect a common influence
      of androgen exposure. The possible roles of temporal and localized effects of
      masculinization are discussed.

PMID- 18080737
TI  - Human variability of fMRI brain activation in response to oculomotor stimuli.
AB  - Assessing interindividual variability of brain activation is of practical
      importance to the use of functional magnetic resonance imaging (fMRI) in the
      clinical context. The main objective of this study is to analyze the variability
      of the oculomotor system through horizontal optokinetic, pursuit and saccadic eye
      movement stimulations by means of fMRI. We found significant activation of many
      cortical and subcortical structures. The frequency of activation demonstrates a
      high variability between subjects. However, the most frequent activation regions
      were located in frontal areas and in regions comprising the middle temporal and
      medial superior temporal areas. Our study allowed the characterization of the
      most frequently involved foci in optokinetic stimulation, pursuit and saccadic
      eye movement tasks. The combination of these tasks constitutes a suitable tool
      for mapping major areas involved in the oculomotor system.

PMID- 18080738
TI  - Power calculations using exact data simulation: a useful tool for genetic study
      designs.
AB  - Statistical power calculations constitute an essential first step in the planning
      of scientific studies. If sufficient summary statistics are available, power
      calculations are in principle straightforward and computationally light. In
      designs, which comprise distinct groups (e.g., MZ & DZ twins), sufficient
      statistics can be calculated within each group, and analyzed in a multi-group
      model. However, when the number of possible groups is prohibitively large (say,
      in the hundreds), power calculations on the basis of the summary statistics
      become impractical. In that case, researchers may resort to Monte Carlo based
      power studies, which involve the simulation of hundreds or thousands of replicate
      samples for each specified set of population parameters. Here we present exact
      data simulation as a third method of power calculation. Exact data simulation
      involves a transformation of raw data so that the data fit the hypothesized model
      exactly. As in power calculation with summary statistics, exact data simulation
      is computationally light, while the number of groups in the analysis has little
      bearing on the practicality of the method. The method is applied to three genetic
      designs for illustrative purposes.

PMID- 18080739
TI  - Risk behaviors of homeless men in India: a potential bridge population for HIV
      infection.
AB  - This study investigated whether homeless men are a bridge group for transmission
      of HIV to the general population in India. A cross-sectional study design was
      used to measure subjects' past and current sexual activities. We surveyed 493 of
      606 homeless men aged 18-49 years who live in public places in Kolkata, India,
      who were invited to take part in a structured interview, using a CD player and
      earphones. Almost two-thirds of respondents had never attended school. Sex with
      commercial sex worker (CSWs), multiple sex partners, and inconsistent condom use
      were common. About 90% of married homeless men visited CSWs, but only 3.3%
      consistently used condoms. AIDS awareness and risk perception were very low. Less
      education and being married but not currently living with wife were associated
      with high-risk sexual behaviors. Homeless men should be considered a potential
      bridge for HIV transmission from CSWs to the general population. Appropriate non
      written communication strategies targeted to homeless people are urgently needed.
      Community intervention programs targeting the homeless, such as the 'Popular
      Opinion Leader' model, should be designed and evaluated.

PMID- 18080741
TI  - Therapist turnover and new program sustainability in mental health clinics as a
      function of organizational culture, climate, and service structure.
AB  - The present study incorporates organizational theory and organizational
      characteristics in examining issues related to the successful implementation of
      mental health services. Following the theoretical foundations of socio-technical
      and cultural models of organizational effectiveness, organizational climate,
      culture, legal and service structures, and workforce characteristics are examined
      as correlates of therapist turnover and new program sustainability in a
      nationwide sample of mental health clinics. Results of General Linear Modeling
      (GLM) with the organization as the unit of analysis revealed that organizations
      with the best climates as measured by the Organizational Social Context (OSC)
      profiling system, had annual turnover rates (10%) that were less than half the
      rates found in organizations with the worst climates (22%). In addition,
      organizations with the best culture profiles sustained new treatment or service
      programs over twice as long (50 vs. 24 months) as organizations with the worst
      cultures. Finally, clinics with separate children's services units had higher
      turnover rates than clinics that served adults and children within the same unit.
      The findings suggest that strategies to support the implementation of new mental
      health treatments and services should attend to organizational culture and
      climate, and to the compatibility of organizational service structures with the
      demand characteristics of treatments.

PMID- 18080742
TI  - Distinguishing proactive and reactive aggression in Chinese children.
AB  - This study examined proactive and reactive aggression and their relation to
      psychosocial adjustment in three samples (N = 767, 368 girls, M age = 10.03) of
      Chinese school age children. Confirmatory factor analyses revealed that a two
      factor model which distinguished both proactive and reactive aggression fit the
      data reasonably well, and also fit the data better than a single-factor model in
      all three samples. The distinction between proactive and reactive aggression was
      found for both boys and girls. Reactive aggression was more strongly related to
      reciprocated friendship (negatively), peer victimization, emotion dysregulation,
      hostile attributions of others' behavior in ambiguous social situations, and self
      reported loneliness and social anxiety (positively) than was proactive
      aggression. Proactive aggression was related to positive outcome expectancies and
      efficacy beliefs of aggression for boys but not for girls, but the significant
      gender difference was only found for positive outcome expectancies. The findings
      suggest that proactive and reactive aggression represent two distinct forms of
      aggression which are associated with specific adjustment outcomes in Chinese
      children.

PMID- 18080743
TI  - Making the connections: community capacity for tobacco control in an urban
      African American community.
AB  - Developing community capacity to improve health is a cornerstone of community
      based public health. The concept of community capacity reflects numerous facets
      and dimensions of community life and can have different meanings in different
      contexts. This paper explores how members of one community identify and interpret
      key aspects of their community's capacity to limit the availability and use of
      tobacco products. Particular attention is given to examining the
      interrelationship between various dimensions of community capacity in order to
      better understand the processes by which communities are able to mobilize for
      social change. The study is based on qualitative analysis of 19 in-depth
      interviews with key informants representing a variety of community sectors in
      Harlem, New York City. Findings indicate that the community is viewed as rich in
      human and social resources. A strong sense of community identity and
      connectedness underlies this reserve and serves as a catalyst for action.

PMID- 18080744
TI  - The sacred character of community life.
AB  - Theory and research suggest that there is a basic and irreducible human yearning
      for a relationship with something that transcends ourselves, something sacred.
      The sacred can be understood not only in individual terms, but also in terms of
      relationships, settings, and communities. Empirical studies indicate that the
      sacred has powerful implications for human behavior; it can be an organizing
      force and a resource to people in their most difficult times, yet it can also be
      a source of seemingly intractable problems. This paper reviews several of the
      promising steps psychologists have taken to learn about the sacred, learn from
      spiritual communities, and collaborate with these communities in efforts to
      better the world. Research and practice in this area is enriching our
      understanding of the meaning of community and the meaning of spirituality.

PMID- 18080745
TI  - The association of daily hassles and uplifts with family and life satisfaction:
      does cultural orientation make a difference?
AB  - The study examined similarities and differences between people having
      individualist and collectivist cultural orientations in terms of what they
      perceive as stressful and uplifting experiences in their daily lives, and the
      relation between daily experiences and family and life satisfaction. Data were
      collected from two representative community samples (697 Jews and 303 Arabs).
      Each sample was grouped into individualist and collectivist cultural
      orientations. The two cultural orientation groups differed with respect to the
      appraisal of positive and negative daily experiences. A structural equation
      modeling (SEM) multi-group analysis indicated a similar factor structure for
      hassles and uplifts in both groups. However, the two groups differed in the
      effects of positive and negative daily occurrences on family and life
      satisfaction.

PMID- 18080746
TI  - FK506 protects neurons following peripheral nerve injury via immunosuppression.
AB  - In this study, we have evaluated neuroprotective effect of an immunosuppressant
      immunophilin ligand, FK506, in the sciatic nerve injury model in rats. FK506 was
      injected to the sciatic nerve transected 3-month-old female Wistar rats (2
      mg/kg/day starting 1 day prior to sciatic nerve injury up to 7 day post
      operation). Equal number of sciatic nerve transected animals served as injured
      untreated controls. The contralateral side served as respective control. L4-L5
      region of the spinal cord was removed on day 1, 3, 7, 14, 21, and 28, post
      operation and then processed for cryo-sectioning and paraffin sectioning. The
      cryocut sections were used for immunohistochemistry for localizing all microglia
      (using anti-Iba-1) and MHC-II expressing microglia (with OX-6). The physical
      dissector method was applied on Nissl stained paraffin sections for absolute
      motor neuron counting in the L4-L5 region of spinal cord. FK506 treated animals
      presented 88.7% neuronal survival while the injured alone had 79.12%, which is
      significantly less than the treated animals. FK506 caused early proliferation of
      microglia at 1 and 3 days post operation. FK506 also significantly restricted
      transformation of these cells in to phagocytes. Colocalization of activated
      microglia by anti-Iba-1 and OX-6 antibodies, confirms that the MHC-II expressing
      cells in injured spinal cord are none other than microglial cells and MHC-II
      expressing cells are significantly less in treated as compared to untreated
      injured animals. We propose that immunosuppression is one of the main mechanisms
      by which FK506 protects the central neurons following peripheral injury.

PMID- 18080747
TI  - The LCT 13910 C/T polymorphism as a risk factor for osteoporosis, has no impact
      on metastatic bone disease in breast cancer.

PMID- 18080748
TI  - The potential risk of neoadjuvant chemotherapy in breast cancer patients--results
      from a prospective randomized trial of the Austrian Breast and Colorectal Cancer
      Study Group (ABCSG-07).
AB  - PURPOSE: To evaluate the impact that pre- and postoperatively administered
      chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF) and
      postoperative chemotherapy vs. postoperative chemotherapy alone have on long-term
      prognosis. PATIENTS AND METHODS: The ABCSG conducted a nationwide randomized
      phase III trial in high-risk endocrine non-responsive breast cancer patients
      comparing pre- and postoperative chemotherapy containing CMF as preoperative
      treatment vs. postoperative chemotherapy alone between 1991 and 1999. From 1996
      the ABCSG-07 protocol was amended to also allow randomization of high-risk
      endocrine-responsive patients. Of 423 eligible patients with high-risk primary
      breast cancer, 203 patients were randomly assigned to preoperatively receive
      three cycles of CMF (cyclophosphamide, methotrexate, fluorouracil; 600/40/600
      mg/m(2)) intravenously on day 1 and 8, while 195 patients received postoperative
      chemotherapy alone. In both groups, three cycles of CMF were given initially, and
      another three cycles of CMF were administered in node-negative patients, whereas
      node-positive patients received three cycles of EC (epirubicin, cyclophosphamide;
      70/600 mg/m(2)). RESULTS: Overall response rate to preoperative chemotherapy with
      three cycles of CMF was 56.2%; complete pathological response was achieved in 12
      patients (5.9%). Recurrence-free survival was significantly better in patients
      receiving chemotherapy postoperatively (HR 0.7, 0.515-0.955; P = 0.024). No
      survival difference was observed between the two therapy groups (HR 0.800, 0.563
      1.136; P = 0.213). DISCUSSION: Preoperative chemotherapy with CMF has to be
      considered as insufficient in high-risk breast cancer patients. Delayed surgery
      and anthracycline-based chemotherapy result in shorter recurrence-free survival
      but not overall survival.

PMID- 18080750
TI  - Proteomic study of the effects of complex environmental stresses in the livers of
      goldfish (Carassius auratus) that inhabit Gaobeidian Lake in Beijing, China.
AB  - Recent advances in proteomics have provided an excellent opportunity to
      understand biological adaptation under complex environmental stress at the
      protein level. Gaobeidian Lake, located in Beijing, China, is characterized by
      complex environmental stresses by serving as both the effluent of a wastewater
      treatment plant and a coolant of a nearby thermal power plant. Liver is the
      primary organ of energy metabolism and xenobiotic detoxification. To further our
      understanding of how organisms that live in Gaobeidian Lake acclimatize
      themselves to these complex environmental stresses, hepatic protein expression
      patterns were examined in goldfish Carassius auratus that inhabit the lake.
      Huairou Reservoir, a drinking water source, was used as a reference site. Twenty
      four protein spots, which were differently expressed in the two sites, were
      further digested with trypsin and analyzed by matrix-assisted laser
      desorption/ionization (MALDI) tandem time of flight mass spectrometry (TOF/TOF).
      The expression of several energy metabolism and oxidative stress proteins, such
      as glutathione peroxidase (GPx), ferritin H3, and liver basic fatty acid-binding
      protein (Lb-FABP) were found to be altered in this stressful environment. In
      addition to the up-regulation of GPx translation, both the mRNA levels and
      enzymatic activity of GPx protein were elevated in goldfish living in Gaobeidian
      Lake. The expression of both peroxisome proliferator activated receptor (PPAR),
      one of the most important metabolism and stress regulation genes as well as
      cytochrome P450 1A1 (CYP1A1), a detoxification gene, was also detected by real
      time PCR at the two sites. Increased expression levels of both PPAR-beta and
      CYP1A1 (P < 0.1) were observed in Gaobeidian Lake. Our study provides an
      integrative view of the expression levels of hepatic proteins and genes in
      goldfish under complex environmental stress that live in Gaobeidian Lake. Our
      results showed that anthropogenic environmental stresses in Gaobeidian Lake
      activated the regulation gene of lipid metabolism PPAR, elevated the lipid
      metabolism levels, and activated the anti-oxidative adaptation mechanism of
      organisms in the lake.

PMID- 18080749
TI  - Simplified apoptotic cascades.
AB  - Apoptosis is an evolutionarily conserved mode of cell death that is tightly
      regulated and critical for multicellular organism development and cellular
      homeostasis. Specific biochemical and morphological changes characterise cells
      undergoing apoptosis, and reflect the specificity in which activated apoptotic
      pathways follow. The two best-characterized apoptotic pathways are the extrinsic
      pathway and the intrinsic pathway, which involve cell surface death receptors and
      the mitochondria and endoplasmic reticulum respectively. Apoptotic stimuli lead
      to activation of either or both of these pathways, and involve sequential
      activation of different cysteine proteases (caspases), and in the case of the
      intrinsic pathway, activation of a family of Bcl-2 proteins that critically
      regulate cell death. Conversely, dis-inhibition of endogenous inhibitors is often
      required for effective apoptotic cell death. Furthermore, an interesting
      recurring protein-protein interaction within this framework of apoptotic cascades
      involves interactions between death domain motifs that are present on many of the
      regulatory proteins in both apoptotic pathways. Cardiomyocyte apoptosis has been
      demonstrated in human heart failure and in rodents, apoptosis itself directly
      causes dilated cardiomyopathy. Understanding the intricacies of apoptotic death
      pathways and determining the relevance of these to cardiomyopathy is therefore
      essential if cardiomyocyte apoptosis is to be a pharmacological target for heart
      failure therapy.

PMID- 18080752
TI  - Analysis of a vesicular glutamate transporter (VGLUT2) supports a cell-leakage
      mode in addition to vesicular packaging.
AB  - VGLUT2 is one of three vesicular glutamate transporters that play crucial roles
      in glutamatergic excitatory neurotransmission. We explored the functional
      properties of the rat VGLUT2 by heterologous expression of VGLUT2 in Xenopus
      oocytes. Immunocytochemical analysis indicated that most VGLUT2 protein was
      expressed in intracellular compartments but that some expression occurred also on
      the plasma membrane. Functional analysis revealed VGLUT2 to be active in two
      independent modes, namely, uptake into intracellular organelles and efflux at the
      plasma membrane. VGLUT-specific transport was identified based on the strong
      preference for glutamate over aspartate--in contrast to plasma-membrane or
      mitochondrial glutamate transporters--and sensitivity to known VGLUT blockers.
      VGLUT2 expression in oocytes (1) stimulated the influx of L-[(3)H]glutamate, but
      not D-[(3)H]aspartate, into digitonin-permeabilized oocytes and (2) stimulated
      efflux of L-glutamate, but not L-aspartate, from intact oocytes preinjected with
      (3)H-labeled amino acids. In the latter assay, cellular efflux of glutamate
      (which was blocked by rose bengal and trypan blue) may be analogous to vesicular
      packaging of glutamate. Our data are consistent with VGLUT2-mediated H(+)/L
      glutamate antiport, but not antiport with chloride. Expression of mammalian
      VGLUT1 and VGLUT3 also stimulated L-[(3)H]glutamate efflux from Xenopus oocytes,
      suggesting that this phenomenon is a general feature of vesicular glutamate
      transporters. Our findings support the idea that vesicular glutamate
      transporters, when transiently expressed on the neuronal plasma membrane, may
      mediate Ca(2+)-independent glutamate leakage in addition to their traditional
      role of packaging glutamate into synaptic vesicles for Ca(2+)-dependent
      exocytosis.

PMID- 18080753
TI  - Age- and sex-dependent differential interaction of nuclear trans-acting factors
      with Fmr-1 promoter in mice brain.
AB  - We have investigated relation between interaction of the trans-acting factors
      with Fmr-1 promoter and expression of FMRP isoforms in intact mouse brain as a
      function of age and sex. Our EMSA data reveal that among the three complexes
      formed with 136 bp Fmr-1 promoter fragment, the level of complex C1 significantly
      increases in adult brain but decreases in old brain in comparison to that in
      young. The level of total FMRP significantly decreases from young to old in the
      brain of both the sexes, however, among the three isoforms, expression of the 80
      kDa isoform significantly decreases in the brain of both the sexes where as the
      level of 70 kDa isoform decreases in females during aging. The present finding on
      relation between age- and sex-dependent interaction of trans-acting factors and
      expression of FMRP isoforms is novel and may be relevant for regulation of Fmr-1
      gene in brain function during aging.

PMID- 18080754
TI  - Complexity of depolarization-mediated ERK phosphorylation in cerebellar granule
      cells in primary cultures.
AB  - We previously showed that cultured mouse cerebellar granule cells during
      incubation in glutamine-replete medium respond to 45 mM [K(+)](e) after 20 and 60
      min incubation with extracellular-signal regulated kinase 1 and 2 (ERK(1/2))
      phosphorylation which is mainly, but probably not exclusively, secondary to
      glutamate release and transactivation of epidermal growth factor (EGF) receptors.
      In the present study the response after 20 min was shown to be abolished by
      protein kinase C (PKC) inhibition, whereas that at 60 min was PKC-independent.
      Addition of 50 microM glutamate to the cells caused ERK(1/2) phosphorylation
      already after 5 min most of which was sensitive to PKC inhibition although a
      minor part was PKC inhibition-resistant. Exposure to [K(+)](e) during incubation
      in glutamine-depleted medium caused no stimulated release of glutamate but a
      transactivation-independent ERK(1/2) phosphorylation at 20 and 60 min. The
      response at 20 min was insensitive to PKC inhibition. The potential importance of
      these complex responses for synaptic plasticity is discussed.

PMID- 18080755
TI  - Optimal design for epidemiological studies subject to designed missingness.
AB  - In large epidemiological studies, budgetary or logistical constraints will
      typically preclude study investigators from measuring all exposures, covariates
      and outcomes of interest on all study subjects. We develop a flexible theoretical
      framework that incorporates a number of familiar designs such as case control and
      cohort studies, as well as multistage sampling designs. Our framework also allows
      for designed missingness and includes the option for outcome dependent designs.
      Our formulation is based on maximum likelihood and generalizes well known results
      for inference with missing data to the multistage setting. A variety of
      techniques are applied to streamline the computation of the Hessian matrix for
      these designs, facilitating the development of an efficient software tool to
      implement a wide variety of designs.

PMID- 18080756
TI  - Are assertive community treatment and recovery compatible? Commentary on "ACT and
      recovery: integrating evidence-based practice and recovery orientation on
      assertive community treatment teams".

PMID- 18080757
TI  - Sensitivity analysis and model assessment: mathematical models for arterial blood
      flow and blood pressure.
AB  - The complexity of mathematical models describing the cardiovascular system has
      grown in recent years to more accurately account for physiological dynamics. To
      aid in model validation and design, classical deterministic sensitivity analysis
      is performed on the cardiovascular model first presented by Olufsen, Tran,
      Ottesen, Ellwein, Lipsitz and Novak (J Appl Physiol 99(4):1523-1537, 2005). This
      model uses 11 differential state equations with 52 parameters to predict arterial
      blood flow and blood pressure. The relative sensitivity solutions of the model
      state equations with respect to each of the parameters is calculated and a
      sensitivity ranking is created for each parameter. Parameters are separated into
      two groups: sensitive and insensitive parameters. Small changes in sensitive
      parameters have a large effect on the model solution while changes in insensitive
      parameters have a negligible effect. This analysis was successfully used to
      reduce the effective parameter space by more than half and the computation time
      by two thirds. Additionally, a simpler model was designed that retained the
      necessary features of the original model but with two-thirds of the state
      equations and half of the model parameters.

PMID- 18080758
TI  - Nonlinear assessment of cerebral autoregulation from spontaneous blood pressure
      and cerebral blood flow fluctuations.
AB  - Cerebral autoregulation (CA) is an most important mechanism responsible for the
      relatively constant blood flow supply to brain when cerebral perfusion pressure
      varies. Its assessment in nonacute cases has been relied on the quantification of
      the relationship between noninvasive beat-to-beat blood pressure (BP) and blood
      flow velocity (BFV). To overcome the nonstationary nature of physiological
      signals such as BP and BFV, a computational method called multimodal pressure
      flow (MMPF) analysis was recently developed to study the nonlinear BP-BFV
      relationship during the Valsalva maneuver (VM). The present study aimed to
      determine (i) whether this method can estimate autoregulation from spontaneous BP
      and BFV fluctuations during baseline rest conditions; (ii) whether there is any
      difference between the MMPF measures of autoregulation based on intra-arterial BP
      (ABP) and based on cerebral perfusion pressure (CPP); and (iii) whether the MMPF
      method provides reproducible and reliable measure for noninvasive assessment of
      autoregulation. To achieve these aims, we analyzed data from existing databases
      including: (i) ABP and BFV of 12 healthy control, 10 hypertensive, and 10 stroke
      subjects during baseline resting conditions and during the Valsalva maneuver, and
      (ii) ABP, CPP, and BFV of 30 patients with traumatic brain injury (TBI) who were
      being paralyzed, sedated, and ventilated. We showed that autoregulation in
      healthy control subjects can be characterized by specific phase shifts between BP
      and BFV oscillations during the Valsalva maneuver, and the BP-BFV phase shifts
      were reduced in hypertensive and stroke subjects (P < 0.01), indicating impaired
      autoregulation. Similar results were found during baseline condition from
      spontaneous BP and BFV oscillations. The BP-BFV phase shifts obtained during
      baseline and during VM were highly correlated (R > 0.8, P < 0.0001), showing no
      statistical difference (paired-t test P > 0.47). In TBI patients there were
      strong correlations between phases of ABP and CPP oscillations (R = 0.99, P <
      0.0001) and, thus, between ABP-BFV and CPP-BFV phase shifts (P < 0.0001, R =
      0.76). By repeating the MMPF 4 times on data of TBI subjects, each time on a
      selected cycle of spontaneous BP and BFV oscillations, we showed that MMPF had
      better reproducibility than traditional autoregulation index. These results
      indicate that the MMPF method, based on instantaneous phase relationships between
      cerebral blood flow velocity and peripheral blood pressure, has better
      performance than the traditional standard method, and can reliably assess
      cerebral autoregulation dynamics from ambulatory blood pressure and cerebral
      blood flow during supine rest conditions.

PMID- 18080759
TI  - Arterial baroreflexes and cardiovascular modeling.
AB  - Many cardiovascular models involve prediction of changes that occur when a
      subject is perturbed in some way, to move from one state to another. A
      successful, predictive model should involve at least two elements: First, the
      model should include some index of the intensity of the perturbation that elicits
      the response; effective responses should, in some fashion, be linearly or
      nonlinearity related to perturbations. Second, the model should factor in
      subjects' abilities to meet the challenges posed by the perturbations. This
      review indicates that these two basic components of a successful model may be
      difficult to incorporate. In the simple case of passive upright tilt, blood
      pressure measurements may not accurately indicate the stimulus, because blood
      pressure reductions are reversed by rapidly occurring reflex blood pressure
      increases. Since not all subject populations respond identically to hemodynamic
      challenges, it also may be important to characterize baroreflex responsiveness,
      and include such a term in a model. Although vagal and sympathetic baroreflex
      responses to stereotyped challenges can be measured accurately, recent research
      points to extraordinary variability of baroreflex responsiveness. The
      complexities discussed in this review should be considered, whether they are, or
      even can be incorporated into cardiovascular models.

PMID- 18080760
TI  - Concurrent inflammatory bowel disease and myelodysplastic syndrome: report of
      nine new cases and a review of the literature.
AB  - Nine patients with concurrent myelodysplastic syndrome (MDS) and inflammatory
      bowel disease (IBD) were examined. Median age at diagnosis of these patients was
      similar to the usual age of patients at diagnosis of IBD only. There was a strong
      predominance of Crohn's disease (seven of nine cases), with an unusually high
      frequency of colorectal involvement (five of nine cases). Inflammatory bowel
      disease was diagnosed first in one patient, MDS first in five patients, and both
      diseases were diagnosed simultaneously in three patients. All patients had
      moderate or severe anemia. The prognosis of IBD was determined by MDS. These
      observations suggest that there is an unclear common pathogenesis of IBD and MDS
      and, consequently that patients with IBD and anemia of non-obvious origin should
      be evaluated for the presence of MDS.

PMID- 18080761
TI  - Management of de novo hepatocellular carcinoma developing in a transplanted
      liver.

PMID- 18080762
TI  - Cytokine levels of TGF-beta, IL-10, and sTNFalphaRII in type C chronic liver
      disease.
AB  - Cytokines play a key role in regulation of immunity and inflammation. The aim of
      the study was to detect serum levels of TGF-beta, IL-10, and sTNFalphaRII in
      patients with type C chronic liver disease (CLD) and to correlate these with
      biochemical and histopathological parameters used to assess the severity of the
      disease. Blood samples were aseptically collected from 90 CLD patients. Cytokine
      levels were also followed up in 39 chronic hepatitis cases. Levels of the
      cytokines in 90 CLD patients were significantly higher than in controls. In the
      follow up patients, 12 were non-responders and the serum levels of cytokines were
      still elevated after therapy whereas in 27 responders cytokine levels were
      significantly reduced after therapy and correlated well with biochemical and
      histopathological parameters. It is inferred that cytokine levels reflect the
      level of inflammation in chronic hepatitis C virus (HCV) infection and can be
      used as indirect markers to assess the severity of liver disease.

PMID- 18080763
TI  - Interferon beta 1a versus interferon beta 1a plus ribavirin for the treatment of
      chronic hepatitis C in Chinese patients: a randomized, placebo-controlled trial.
AB  - For chronic hepatitis C virus (HCV) infection, the effects of current therapies
      are limited. To evaluate the efficacy and safety of the interferon beta-1a (IFN
      beta-1a) versus IFN beta-1a plus ribavirin (RBV) combination on Chinese treatment
      naive patients with chronic hepatitis C, a randomized, placebo-controlled study
      was performed. A total of 26 naive patients histologically confirmed to have
      chronic hepatitis C were double-blindly and randomly assigned to receive either
      IFN beta-1a 44 microg (12 MIU) (IFN beta-1a group) or placebo (placebo group)
      three times per week for 12 weeks. At the end of the 12 weeks of treatment, the
      patients who received IFN beta-1a continued to complete 24 weeks of treatment.
      Placebo non-responders were crossed over to IFN beta-1a plus RBV (1,000-1,200
      mg/day) combination therapy (IFN beta-1a plus RBV group) for 24 weeks after 4
      weeks washout. All patients were followed up for 24 weeks after the end of
      treatment. Sustained virological response (SVR) was defined as the absence of
      detectable HCV RNA in the serum both at the end of 24 weeks of treatment and at
      the end of 24 weeks of untreated follow-up. There were no differences in the
      clinical background between the groups before the initiation of treatment. At the
      end of the 12 weeks of double-blind therapy, HCV RNA was negative and
      undetectable in 10/11 patients (90.9%) in the IFN beta-1a group and none in the
      placebo group. The virological response rate (14/15, 93.3%) of the IFN beta-1a
      plus RBV group at week 12 after the initiation of therapy was similar to that of
      the IFN beta-1a group. SVR was observed in 5/11 (45.5%) of the IFN beta-1a group
      and 11/15 (73.3%) of the IFN beta-1a plus RBV group (P = 0.23). At the end of
      follow-up, a biochemical response was found in 5/11 patients in the IFN beta-1a
      group (45.5%) and 8/15 patients in the IFN beta-1a plus RBV group (53.3%, P =
      1.00). Multiple logistic regression analysis confirmed that an HCV RNA load lower
      than 1.0x10(6) copies/ml was independently associated with SVR (OR 11.00; 95% CI
      1.81-66.97; P = 0.003). The side effects were mild and similar in the two therapy
      groups. We conclude that IFN beta-1a alone or in combination with RBV provided
      considerable benefit in Chinese naive patients with chronic hepatitis C.
      Treatments with IFN beta-1a alone or IFN beta-1a plus RBV are safe and well
      tolerated, and may represent an alternative for chronic hepatitis C patients who
      are unable to tolerate pegylated interferon alpha.

PMID- 18080764
TI  - Increased prevalence of gallstone disease and impaired gallbladder motility in
      patients with Barrett's esophagus.
AB  - The prevalence of gallstones in patients with Barrett's esophagus (BE) and their
      gallbladder motility relative to that of healthy volunteers and GERD patients
      without BE were investigated. Of the 707 patients reviewed, 203 (125 males and 78
      females) had BE. The prevalence of gallstones was significantly higher in the
      patients with BE than in those without BE (34 vs. 20%, respectively). The
      gallbladder functions of 22 patients with GERD, 27 patients with BE and 21
      healthy volunteers were assessed by ultrasonography before and after a test meal.
      The patients with BE had significantly higher fasting volume and residual volume,
      but lower ejection volume, ejection fraction and ejection rate values than those
      of the healthy controls. None of the ultrasonographic parameters of patients
      without BE were significantly different from those of the controls. Patients with
      BE have a more complex gastrointestinal motility disorder that involves the
      gallbladder, and this makes this subset of patients with GERD more prone to
      gallstone disease.

PMID- 18080765
TI  - Predictive factors for clinical improvement with Enterra gastric electric
      stimulation treatment for refractory gastroparesis.
AB  - The objectives of this study were to determine the clinical response to Enterra
      gastric electric stimulation (GES) in patients with refractory gastroparesis and
      to determine factors associated with a favorable response. METHODS: This study
      was conducted in patients undergoing Enterra GES for refractory gastroparesis.
      Symptoms were scored before and after GES implantation using the Gastroparesis
      Cardinal Symptom Index (GCSI) with additional questions about abdominal pain and
      global clinical response. RESULTS: During an 18-month period, 29 patients
      underwent GES implantation. Follow-up data were available for 28 patients, with
      average follow-up of 148 days. At follow-up, 14 of 28 patients felt improved, 8
      remained the same, and 6 worsened. The overall GCSI significantly decreased with
      improvement in the nausea/vomiting subscore and the post-prandial subscore, but
      no improvement in the bloating subscore or abdominal pain. The decrease in GCSI
      was greater for diabetic patients than idiopathic patients. Patients with main
      symptom of nausea/vomiting had a greater improvement than patients with the main
      symptom of abdominal pain. Patients taking narcotic analgesics at the time of
      implant had a poorer response compared to patients who were not. CONCLUSIONS: GES
      resulted in clinical improvement in 50% of patients with refractory
      gastroparesis. Three clinical parameters were associated with a favorable
      clinical response: (1) diabetic rather than idiopathic gastroparesis, (2)
      nausea/vomiting rather than abdominal pain as the primary symptom, and (3)
      independence from narcotic analgesics prior to stimulator implantation. Knowledge
      of these three factors may allow improved patient selection for GES.

PMID- 18080766
TI  - Expression and prognostic roles of Eag1 in resected esophageal squamous cell
      carcinomas.
AB  - Expression of Eag1 was detected in resected esophageal squamous cell carcinomas
      tissues and matched tissues by immunohistochemistry and RT-PCR. Positive
      expression of Eag1 protein was 75% (51/68), and mRNA was 73% (8/11) in primary
      cancer tissues. Eag1 protein positively stained in all 10 metastatic lymph nodes.
      Eag1 protein and mRNA were negatively expressed in all non-cancerous matched
      tissues. Eag1 protein was associated with depth of penetration (P = 0.023), but
      not associated with other clinicopathological factors. Eag1 protein positive
      group had a significantly shorter survival time than the negative group (P =
      0.005). Survival rates at each time-point for the positive group were lower than
      that for the negative group (P = 0.006), and Eag1 was identified as an
      independent prognostic factor of long-term survival (P = 0.016). In conclusion,
      Eag1 was aberrantly expressed in ESCC and correlated with poor prognosis after
      surgery.

PMID- 18080767
TI  - Abberant crypt foci -- importance in colorectal carcinogenesis and expression of
      p53 and mdm2: a changing concept.
AB  - BACKGROUND: The presence of aberrant crypt foci (ACF) represents an important
      preneoplastic condition of the large intestine. The ACF are used extensively as
      the biological end point to study the effects of diet, biological agents and
      chemotherapeutic agents as they undergo distinct morphological and genetic
      changes in response to these factors. Till date, in human ACF, K-ras, beta
      catenin, carcinoembryonic antigen (CEA) and adenomatous polyposis coli (APC)
      protein expression have been investigated, but the expression of late markers of
      colon carcinogenesis have not been studied in great detail. AIMS: To study the
      significance of ACF in carcinogenesis, the incidence of ACF in colorectal
      carcinoma (CRC) patients and the expression profiles of the tumor repressor
      protein p53 and the murine double minute (mdm2) protein in ACF. METHODS AND
      MATERIALS: The pattern of expression, histology and immunohistochemistry of the
      p53 and mdm2 proteins were studied in 32 colectomy specimens. Careful scoring was
      carried out using standard criteria. The prevalence of ACF, types of ACF,
      surrounding mucosal changes and the relation of ACF with tumor morphology and
      aggressiveness were determined, as was any difference in the staining pattern
      between hyperplastic and dysplastic ACF. RESULT: Aberrant crypt foci were present
      in a large number of cases (84.4%), of which 65% were hyperplastic. All
      hyperplastic and dysplastic ACF tested positive for p53 in the nucleus. Both the
      nucleus and cytoplasm tested positive for mdm2 irrespective of the degree of
      dysplasia. No correlation was noted between ACF and tumor histology. CONCLUSION:
      The p53 and mdm2 proteins are expressed during the very early stages of mucosal
      changes in ACF, irrespective of histological changes, but the pattern of
      expression can differ depending on geographical barriers, genetic factors, diet
      and environmental conditions. This results suggests that the conventional adenoma
      carcinoma sequence is not completely correct. The detection of ACF and p53 and
      mdm2 expression can help to curtail the disease in its early stage by targeted
      therapy.

PMID- 18080769
TI  - The relationship between severity of liver cirrhosis and pulmonary function
      tests.
AB  - Pulmonary complications, mainly hepatopulmonary syndrome (HPS), are frequently
      observed in liver cirrhosis. In this study, the aim was to investigate the
      frequency of hypoxemia and impairment of pulmonary function tests (PFT) in
      patients with liver cirrhosis and to examine the relationships of these
      impairments with liver failure. A total of 39 patients with cirrhosis, 24 males
      and 15 females, were included in our study. The mean age of the patients was 47.5
      +/- 17.2 years. Arterial blood gases, PFT, and carbon monoxide diffusion tests
      (DLCO) were performed in all patients. Out of 39 cirrhotic patients, 21 (53.8%)
      had ascites, whereas 18 (46.2%) did not. Seven patients were in the Child-Pugh A
      group, 21 in the Child-Pugh B group, and 11 patients were in the Child-Pugh C
      group. Hypoxia was found in 33.3% of the patients. Although the PaO2 and SaO2
      values of patients with ascites were lower compared to those without ascites (P <
      0.05), no statistically significant difference was determined in the comparison
      of hypoxia between the groups (P > 0.05). Among the PFT parameters, FEV1/FVC and
      FEF25-75% values were found to be lower in patients with ascites than those
      without (P < 0.05). No differences were established between these two groups of
      patients in terms of DLCO (P > 0.05). While no differences were found in
      comparison of the DLCO values in between the groups (P > 0.05), there was a
      statistically significant difference in the ratio of DLCO to the alveolar
      ventilation (DLCO/VA) in between the groups (P < 0.05). On the other hand, a
      negative correlation was found between the DLCO/VA and Child points when the
      relationship between the Child-Pugh score and PFT parameters were investigated (r
      = -0.371, P < 0.05). Consequently, a relationship was established between the
      severity of liver failure and diffusion tests showing pulmonary complications
      invasively. We believe diffusions tests should be performed in addition to the
      PFT in order to determine pulmonary involvements particularly in patients who are
      candidates for liver transplantation.

PMID- 18080768
TI  - Serum ghrelin levels in inflammatory bowel disease with relation to disease
      activity and nutritional status.
AB  - Ghrelin possesses various biological activities -- it stimulates growth hormone
      (GH) release, plays a major role in energy metabolism, and is one of the hormones
      that affects body composition. It also plays a role in modulating immune response
      and inflammatory processes. In this study we aimed to determine whether serum
      ghrelin levels had correlation with markers associated with disease activation.
      We also investigated any probable relationship between serum ghrelin level and
      nutritional status. Serum levels of ghrelin and its relationship with disease
      activity and nutritional status were evaluated in 34 patients with ulcerative
      colitis (UC), 25 patients with Crohn's disease (CD), and 30 healthy controls.
      Serum ghrelin levels, serum IGF-1 and GH levels, and markers of disease activity
      (sedimentation, C-reactive protein, and fibrinogen) were measured in all
      subjects. Body composition and nutritional status was assessed by both direct (by
      anthropometry) and indirect (by bioimpedance) methods. Serum ghrelin levels were
      significantly higher in patients with active UC and CD than in those in remission
      (108 +/- 11 pg/ml vs. 71 +/- 13 pg/ml for UC patients, P < 0.001; 110 +/- 10
      pg/ml vs. 75 +/- 15 pg/ml for CD patients, P < 0.001). Circulating ghrelin levels
      in UC and CD patients were positively correlated with sedimentation, fibrinogen
      and CRP and was negatively correlated with IGF-1, BMI, TSFT, MAC, fat mass (%),
      and fat free mass (%). This study demonstrates that patients with active IBD have
      higher serum ghrelin levels than patients in remission and high levels of
      circulating ghrelin correlate with the severity of disease and the activity
      markers. Ghrelin levels in inflammatory bowel disease (IBD) patients show an
      appositive correlation with IGF-1 and bioelectrical impedance analysis, body
      composition, and anthropometric assessments. Finally, we arrived at the
      conclusion that ghrelin level may be important in determination of the activity
      in IBD patients and evaluation of nutritional status.

PMID- 18080770
TI  - Getting from the ethical to the empirical and back again: the danger of getting
      it wrong, and the possibilities for getting it right.

PMID- 18080771
TI  - Unpacking the meaning of quality in Quebec's health-care system: the input of
      commissions of inquiry.
AB  - The paper explores how several commissions of inquiry established in Quebec,
      Canada, have, over time, contributed in redefining the meaning of quality in
      health-care and its management. Adopting an interpretive analysis of commissions'
      reports, the paper examines the particular 'conceptual boxes' used by their
      members to tackle quality and the embedded nature of their work. It is shown that
      although quality was always considered, this was generally done by bringing into
      focus specific quality domains and issues, some new, others not so new. In
      addition, the various management approaches to quality featured in the reports
      were informed by evolving templates; although this evolution was not as straight
      and unwavering as some retrospective studies of quality in health-care seem to
      indicate. A common thread to all commissions is the fact that, beyond the
      definition of general principles, responsibility for quality oversight was not
      clearly assigned and criteria on whether quality initiatives should be voluntary
      or compulsory were often left unspecified. Further, quality was never regarded by
      the commissions as a strategic aspect of health-care. It is speculated that these
      failings on the part of commissions may partly explain the unassertive course of
      action taken by the provincial government in the area.

PMID- 18080772
TI  - What transition means for India's city poor.

PMID- 18080774
TI  - Cigarette smoking and risk of epithelial ovarian cancer.
AB  - BACKGROUND: An increased risk of mucinous ovarian tumors among cigarette smokers
      has been observed in multiple studies. The association of smoking with other
      histologic types of ovarian cancer is less clear, but potentially holds greater
      importance for prevention of disease incidence and mortality. METHODS: In a
      population-based study of 812 women with ovarian cancer diagnosed in western
      Washington State from 2002-2005 and 1,313 controls, we assessed the risk
      associated with cigarette smoking, with a particular focus on tumor subgroups
      jointly classified according to the degree of invasiveness and histology.
      Information was collected through in-person interviews, and logistic regression
      was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
      RESULTS: The incidence of both borderline and invasive mucinous ovarian tumors
      was increased among women with a history of cigarette smoking (ORs and 95% CIs =
      1.8, 1.2-2.9, and 1.8, 0.8-4.3, respectively). Increases in risk of these tumor
      types were most evident among women with greater smoking duration and pack-years
      of exposure, and among those who had smoked within the prior 15 years. We noted
      no clear patterns of risk of serous tumors with duration or pack-years of
      smoking; however, risk of these tumor types was somewhat elevated among women who
      had smoked within the previous 15 years (for borderline serous tumors, OR and 95%
      CI = 1.5, 0.9-2.3; for invasive serous tumors, OR and 95% CI = 1.4, 1.1-1.9). The
      risk of endometrioid, clear cell, and the remaining histologic types of invasive
      ovarian cancer was not increased among smokers. CONCLUSION: In the aggregate,
      evidence is insufficient to determine whether smoking is linked with risk of
      serous or other non-mucinous histologic types of ovarian cancer. Studies that
      employ additional histopathologic and molecular techniques to more accurately
      delineate subsets of tumors may improve our understanding of the impact of
      smoking on ovarian cancer risk.

PMID- 18080773
TI  - Expression of intermediate filaments, EGF and TGF-alpha in early human kidney
      development.
AB  - The spatial and temporal expression patterns of cytokeratins, vimentin,
      epithelial growth factor (EGF) and transforming growth factor alpha (TGF-alpha),
      were investigated in the 5-9-week old human mesonephros and metanephros. Vimentin
      was found in all mesonephric structures, while cytokeratins were seen only in the
      mesonephric tubules. EGF and TGF-alpha were detected early in all mesonephric
      structures, and immunoreactivity to both factors decreased in later stages. In
      the 5-6-week metanephros, vimentin immunoreactivity was found in all structures
      and later increased in the collecting system and interstitium. In the 5th week,
      cytokeratins 8 and 19 appeared in the ureteric bud and ampullae, and later showed
      increasing immunoreactivity in the collecting system and nephrons. The
      coexpression of intermediate filament proteins in metanephric development is a
      temporary feature and might be associated with mesenchymal to epithelial
      transformation of developing nephrons. In adult kidneys, such coexpression is
      associated with fibrosis or carcinomatous changes. At early stages,
      immunoreactivity to EGF and TGF-alpha was detected in all metanephric structures
      and from the 7th week onward, it decreased in differentiating nephrons. EGF and
      TGF-alpha patterns of appearance indicate their role in induction, proliferation
      and growth of metanephric structures. Disturbances in that pattern might cause
      reduction in kidney growth.

PMID- 18080775
TI  - Reproductive history in relation to breast cancer risk among Hispanic and non
      Hispanic white women.
AB  - OBJECTIVE: To evaluate reproductive history risk factors in breast cancer among
      Hispanic (HISP) women in the U.S. southwest, a population with approximately 33%
      lower breast cancer incidence than non-Hispanic whites (NHW). METHODS: Population
      based case-control study of HISP (796 cases, 919 controls) and NHW (1,525 cases,
      1,596 controls) women. RESULTS: 19.3% of HISP women reported five or more births
      and had a reduced risk of breast cancer, adjusted odds ratio (OR) 0.70 (95%
      confidence interval (CI): 0.50, 0.98) compared to those with one or two births.
      Breast cancer risk for HISP increased with older age at first birth, p trend =
      0.008. Parity and age at first birth associations were specific to ER positive
      tumors. HISP women who had given birth within five years had higher breast cancer
      risk than women with 16-25 years since a birth, OR 2.62 (95% CI: 1.44, 4.78); the
      trend with years since last birth was stronger than for NHWs, p interaction =
      0.05. CONCLUSIONS: Reproductive history influences on breast cancer risk among
      HISP were similar to associations reported for NHWs. Differences in the
      prevalence of reproductive risk factors would explain an estimated 6.6% lower
      breast cancer incidence for HISP compared to NHWs.

PMID- 18080776
TI  - Tetraiodothyroacetic acid, a small molecule integrin ligand, blocks angiogenesis
      induced by vascular endothelial growth factor and basic fibroblast growth factor.
AB  - Thyroid hormone has been recently shown to induce tumor growth and angiogenesis
      via a plasma-membrane hormone receptor on integrin alphaVbeta3. The receptor is
      at or near the Arg-Gly-Asp (RGD) recognition site on the integrin that is
      important to extracellular matrix (ECM) protein and vascular growth factor
      interactions with the integrin. In the present study, we examined the possibility
      that tetraiodothyroacetic acid (tetrac), a deaminated, non-agonist thyroid
      hormone analog that binds to the integrin receptor, may modulate vascular growth
      factor-induced angiogenesis in the absence of thyroid hormone. Angiogenesis
      models were studied in which VEGF or FGF2 (1-2 microg/ml) induced tube formation
      in human dermal microvascular endothelial cells (HDMEC), stimulated new blood
      vessel branch formation in the chick chorioallantoic membrane (CAM) and induced
      angiogenesis in the mouse matrigel model. In all models, tetrac (1-10 microM) and
      at 10 microg in mouse matrigel inhibited the pro-angiogenesis activity of VEGF
      and FGF2 by more than 50%. RT-PCR revealed that tetrac (1-3 microM) decreased
      abundance of angiopoietin-2 mRNA, but not angiopoietin-1 mRNA, in VEGF-exposed
      endothelial cells, suggesting that specific angiogenic pathways are targeted by
      tetrac. Tetrac is a novel, inexpensive small molecule whose anti-angiogenic
      activity in the present studies is proposed to reflect inhibition, via the
      integrin RGD recognition/thyroid hormone receptor site, of crosstalk between
      plasma-membrane vascular growth factor receptors and integrin alphaVbeta3.

PMID- 18080778
TI  - Spatial patterns in vegetation fires in the Indian region.
AB  - In this study, we used fire count datasets derived from Along Track Scanning
      Radiometer (ATSR) satellite to characterize spatial patterns in fire occurrences
      across highly diverse geographical, vegetation and topographic gradients in the
      Indian region. For characterizing the spatial patterns of fire occurrences,
      observed fire point patterns were tested against the hypothesis of a complete
      spatial random (CSR) pattern using three different techniques, the quadrat
      analysis, nearest neighbor analysis and Ripley's K function. Hierarchical nearest
      neighboring technique was used to depict the 'hotspots' of fire incidents. Of the
      different states, highest fire counts were recorded in Madhya Pradesh (14.77%)
      followed by Gujarat (10.86%), Maharastra (9.92%), Mizoram (7.66%), Jharkhand
      (6.41%), etc. With respect to the vegetation categories, highest number of fires
      were recorded in agricultural regions (40.26%) followed by tropical moist
      deciduous vegetation (12.72), dry deciduous vegetation (11.40%), abandoned slash
      and burn secondary forests (9.04%), tropical montane forests (8.07%) followed by
      others. Analysis of fire counts based on elevation and slope range suggested that
      maximum number of fires occurred in low and medium elevation types and in very
      low to low-slope categories. Results from three different spatial techniques for
      spatial pattern suggested clustered pattern in fire events compared to CSR. Most
      importantly, results from Ripley's K statistic suggested that fire events are
      highly clustered at a lag-distance of 125 miles. Hierarchical nearest neighboring
      clustering technique identified significant clusters of fire 'hotspots' in
      different states in northeast and central India. The implications of these
      results in fire management and mitigation were discussed. Also, this study
      highlights the potential of spatial point pattern statistics in environmental
      monitoring and assessment studies with special reference to fire events in the
      Indian region.

PMID- 18080777
TI  - Genotoxicity screening of the river Rasina in Serbia using the Allium anaphase
      telophase test.
AB  - Evaluation of the presence of genotoxic substances is especially important in
      rivers that serve as a source of drinking water. Nine water samples collected
      along the river Rasina in Serbia were analyzed for potential toxic and genotoxic
      effects using the Allium anaphase-telophase test. Inhibition of root growth
      relative to the negative control (synthetic water) was observed in all samples.
      Analysis of the genotoxic potential, through scoring anaphase and telophase
      aberrations, showed that in seven of the nine samples the level of aberrations
      was significantly increased relative to the negative control but was lower than
      that obtained for the positive control (methyl methanesulfonate). Changes in the
      relation between spindle and chromosome types of aberrations were found in some
      samples, indicating differences in the potential genotoxic substances present at
      the analyzed sites. The data, which were obtained from samples collected at the
      highest level of river water, warn that during periods of low flow the values
      could reach genotoxic activity. The Allium anaphase-telophase test can be
      recommended as an monitoring system, that can serve as the first alert for the
      presence of genotoxic environmental pollutants.

PMID- 18080779
TI  - Ecological restoration of mined-out areas of dry tropical environment, India.
AB  - The objective of the present study was to evince the long-term changes after
      natural revegetation and experimental revegetation of the coal mine spoils with
      respect to total plant biomass, available plant nutrients, nitrogen
      transformation and microbial biomass N (MBN) in dry tropical environment of
      India. Total plant biomass (above- and below-ground), plant available nitrogen,
      soil nitrogen mineralization and microbial biomass N (MBN) were studied for 2
      years in 5 and 10 years old naturally vegetated and revegetated coal mine spoils,
      and dry tropical forest ecosystem of India. In forest ecosystem, the above ground
      biomass values ranged from 3,520 to 3,630 kg ha(-1) and belowground from 6,280 to
      6,560 kg ha(-1). Plant available nitrogen ranged from 16.76 to 23.21 microg g(
      1), net N-mineralization from 9.8 to 48.53 microg g(-1) month(-1) and MBN from
      26.4 to 80.02 microg g(-1). In naturally revegetated mine spoil, the above ground
      biomass values ranged from 1,036 to 1,380 kg ha(-1) and belowground from 2,538 to
      3,380 kg ha(-1). Plant available nitrogen ranged from 7.33-17.14 microg g(-1),
      net N-mineralization from 3.1 to 12.46 microg g(-1) month(-1) and MBN from 14.2
      to 35.44 microg g(-1). In revegetated mine spoil, the above ground biomass values
      ranged from 1,224 to 1,678 kg ha(-1) and belowground from 2,870 to 4,130 kg ha(
      1). Plant available nitrogen ranged from 9.4 to 18.83 microg g(-1), net N
      mineralization from 4.2 to 16.2 microg g(-1) month(-1) and MBN from 21.6 to 42.6
      microg g(-1). The mean plant biomass values in 5 and 10 years mine spoils was
      lower compared to forest ecosystem by 2.5 and 2 times, respectively. N
      mineralization value in 5 year mine spoil was 3.5 times lower and in 10 years
      mine spoil 2 times lower compared to forest ecosystem. The MBN value was about 2
      times lower in both 5 and 10 year mine spoils compared to native forest. MBN was
      positively related to the re-vegetation age of the mine spoil.

PMID- 18080781
TI  - Analysing urban expansion and land use suitability for the city of Kahramanmaras,
      Turkey, and its surrounding region.
AB  - This study aimed at quantifying changes in urban area of the city of
      Kahramanmaras (K.Maras) between 1948 and 2006, and analysing suitability of
      existing land use (LU) to the land potential. Urban change information was
      derived from two black-white monoscopic aerial photographs, and IKONOS and the
      QuickBird images acquired in 1948, 1985, 2000 and 2006, respectively. QuickBird
      image and soil map with 1:25,000 scale were used to analyze suitability of the
      current LU pattern to the land potential. The findings showed that the urban area
      of K.Maras has expanded approximately 13 times during the past six decades.
      According to current LU and the soil map, productive and moderately productive
      soils were largely (73.2%) allocated for agricultural activities, which means
      that there was a strong consistency between the agricultural LU type and the land
      capability. However, widespread agriculture on the non-productive soils, and
      urbanization on the fertile agricultural lands were assessed as unsuitable from
      sustainable LU viewpoint. Considering this phenomenon, it is possible to say that
      rapid urban expansion has a growing pressure on the fertile agricultural soils.
      Monitoring LU changes, particularly urbanization, and developing effective LU
      plans based on the land capability were determined as the most important
      approaches to encourage sustainable use of land.

PMID- 18080780
TI  - Distribution and partition of polycyclic aromatic hydrocarbon in surface water of
      the Pearl River Estuary, South China.
AB  - Water samples were collected in the Pearl River Estuary in July 2002 and April
      2003. The particulate and dissolved phase polycyclic aromatic hydrocarbons (PAHs)
      were determined. Total PAH concentrations in water samples were higher in April
      of 2003 (C (p): 4.0-39.1 ng/L or 445.1-1,089.9 ng/g; C (w): 15.9-184.2 ng/L) than
      in July of 2002 (C (p): 2.6-26.6 ng/L or 297.7-1,336.6 ng/g; C (w): 12.9-28.3
      ng/L). It was found that 5, 6-ring PAHs enrich in the inner estuary samples and
      so did 3-ring PAHs in the July samples. Compositional differences in the
      suspended particulate matter (SPM) might be responsible for this observation. The
      partition coefficient (K (p)) increased with the increasing of the particular
      organic carbon content of suspended particles as well as the salinity of water,
      decreased with the increase of the total suspended particles content of samples.
      A linear correlation between logK (OC) and logK (OW) was found in two sampling
      periods. The observed values of logK (OC) exceed their predicted values derived
      form linear free energy relationship between logK (oc) and logK (ow), which could
      be attributed to the nonlinear sorption of soot-like carbons in suspended
      particles.

PMID- 18080782
TI  - Concentration of Cd, Cu, Pb, Zn, Al, and Fe in soils of Manresa, NE Spain.
AB  - The aims of this study were to determine the contents of cadmium (Cd), copper
      (Cu), lead (Pb), zinc (Zn), aluminium (Al), and iron (Fe) (aqua regia
      extractable) in 27 soil plots (54 samples) from Manresa, NE Spain, and to
      establish relationships between heavy metals and some soil properties. The main
      soil types were surveyed and the median concentrations (mg kg(-1)) obtained were
      Cd 0.28, Cu 20.3, Pb 18.6, Zn 67.4, Al 22,572, and Fe 21,551. Element
      concentrations for these soils were lower than the published values for the
      Valencia region (Spain) and Torrelles and Sant Climent municipal districts
      (Catalonia, Spain). In terms of soil properties, the results of this study
      suggest that, in Manresa soils, both trace element adsorption and retention are
      influenced by several properties such as clay minerals, carbonates, organic
      matter, and pH. All element contents were positively correlated with clay
      content. Pb and Zn were negatively correlated with pH and CaCO(3).

PMID- 18080783
TI  - Incidence of 3-hydroxy-3-methylglutaryl-coenzyme A lyase (HL) deficiency in
      Brazil, South America.
AB  - 3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency (3-hydroxy-3-methylglutaric
      aciduria, 3-HMG) is a rare autosomal recessive inborn error of metabolism
      involving the final step of leucine degradation. HL is the key enzyme for the
      production of glucose-sparing ketone bodies for brain. Positive biochemical
      findings are metabolic acidosis, hyperammonaemia, and hypoketotic hypoglycaemia
      in the neonatal period or infancy. In the present study we report 15 Brazilian
      patients with HL deficiency and present their clinical and biochemical findings.
      Urine from all patients contained large amounts of 3-hydroxy-3-methylglutaric, 3
      methylglutaconic, 3-hydroxyisovaleric and 3-methylglutaric acids, and 3
      methylcrotonylglycine was also observed in 13 patients. The main features at
      clinical presentation were hypoglycaemia (12 patients), seizures (10 patients),
      metabolic acidosis (9 patients), vomiting (6 patients), and hepatomegaly (5
      patients). All but two patients were of Portuguese ancestry. HL deficiency
      comprised 7.3% of total organic acidurias detected in our laboratory during a 13
      year time span, indicating a high incidence of this disorder in Brazil. Limited
      molecular characterization (4/15 patients only) revealed two mutations common for
      individuals of Portuguese/Spanish (Iberian Peninsula) ancestry (E37X and V168fs(
      2)). Our findings increase the number of HL-deficient patients and reinforce the
      characteristic phenotypic picture of the disease. Effective dietary interventions
      based on mild protein restriction and avoidance of fasting and possibly
      alternative C5 ketone body generating therapy for this disorder may provide
      further impetus and rationale for expanded newborn screening of HL deficiency. 

PMID- 18080785
TI  - New mutations of Nogo-C in hepatocellular carcinoma.
AB  - The neurite outgrowth inhibitor Nogo has attracted great interest, but its
      relevance with hepatocellular carcinoma has not been reported. This paper first
      found mutations of Nogo-C in HCC patients from Qidong in China: A172G (Thr58Ala),
      A340G (Arg114Gly), A571G (Ile191Val). In six examined patient cases from Qidong,
      the mutations occurred in five cases. The mutation Arg114Gly was predicted
      bioinformatically to affect Nogo-66 dimensional structure of Nogo-C. Our previous
      works also had indicated that mutant Nogo-C promoted liver cancer cell line
      apoptosis and resulted in molecular marker of HCC p53 gene transfer from nucleus
      to cytoplast. Above results revealed a new physiological role and clinical
      implications of Nogo-C on HCC.

PMID- 18080784
TI  - Establishment of the expression system for studying the function of active
      caspase-3 in zebrafish.
AB  - Caspase-3, a key molecule in apoptosis, has been extensively studied in cell
      culture system; however, it has been less well characterized in vivo because
      certain mediators are required for the proteolytic activation of effector
      caspases, including caspase-3. In this study, various forms of caspase-3 with the
      C-terminal GFP tag were inserted into the pCS2+ plasmid, and the expression
      patterns of caspase-3 proteins were characterized in a zebrafish model system
      using microinjection of nucleic acids into zebrafish embryos. We have verified
      that active caspase-3 was generated by its autocatalytic activity under the
      condition of caspase-2 prodomain (C2P)-caspase-3-GFP overexpression, indicating
      that the C2P domain is crucial for the activation of caspase-3. We also confirmed
      that the C2P domain plays an important role in regulating the nuclear
      localization of the C2P-caspase-3 chimeric protein. We used this expression
      system to establish an animal model system suitable for the investigation of the
      functional characteristics of caspase-3 in vivo. Thus, our study provides a
      useful and specific tool for investigating the molecular mechanisms by which
      active caspase-3 regulates apoptosis during embryonic development.

PMID- 18080786
TI  - Measuring health-related quality of life in Greek children: psychometric
      properties of the Greek version of the Pediatric Quality of Life Inventory(TM)
      4.0 Generic Core Scales.
AB  - OBJECTIVES: The aim of this study was to investigate the psychometric properties
      of the Greek version of the Pediatric Quality of Life Inventory(TM) 4.0
      (PedsQL(TM) 4.0) as a population health outcome measure. METHODS: After cultural
      linguistic validation, a cross-sectional study with the participation of 645
      children (8-12 years old) and their primary caregivers was conducted in a nation
      wide representative school-based sample to evaluate the psychometric properties
      of the measure. RESULTS: All PedsQL 4.0 scales showed satisfactory reliability,
      with Cronbach's alpha exceeding 0.70--except in self-reported Physical
      Functioning (alpha = 0.65). Test-retest stability intraclass correlation
      coefficients (ICCs) were above 0.60 in all subscales. No floor effects were
      detected in either the self-report or parent proxy versions. Ceiling effects
      ranged from 2.2% (self-report Total Score) to 31.1% (parent-report Social
      Functioning). Poor to moderate agreement between self report and proxy report was
      observed, especially for the younger age groups of children. Impact of gender,
      health status, and family affluence status were detected, as hypothesised from
      previous bibliography, with girls reporting lower health-related quality of life
      (HRQOL) than boys on the Emotional Functioning subscale, healthy children scoring
      significantly higher on all scales than those with chronic illnesses, and lower
      socioeconomic groups scoring significantly lower than higher socioeconomic
      groups. Factor analysis showed mainly comparable results with the original
      version. CONCLUSIONS: Present results support the reliability and validity of the
      PedsQL 4.0 Greek version. The instrument could be a valuable tool in HRQOL
      measurement in school health care settings and population-based studies in Greek
      speaking children, though it should be stressed that when possible, the child
      should be considered the first informant of his/her HRQOL.

PMID- 18080787
TI  - Is parental rearing an associated factor of quality of life in adulthood?
AB  - OBJECTIVE: To examine the hypothesis that favorable parental rearing is
      associated with better quality of life in adulthood. METHODS: Two hundred and
      ninety seven university students answered questions on quality of life (WHOQOL
      BREF), parenting style (s-EMBU), coping strategies (Coping Strategies Inventory),
      life events (Social Readjustment Rating Scale) and depressive symptoms (Beck
      Depression Inventory). Data was analyzed by means of hierarchical multiple linear
      regression. RESULTS: The remote variable of perceived child rearing practices was
      significantly associated with the quality of life of the students. Maternal
      emotional warmth was associated with two quality of life domains, psychological
      and social relationships, in addition to global quality of life. CONCLUSION:
      These results strengthen the empirical notion that favorable parental care may be
      associated with better quality of life in adulthood.

PMID- 18080788
TI  - Prolactin levels, breast-feeding and milk production in a cohort of young healthy
      women from high-risk breast cancer families: implications for breast cancer risk.
AB  - High prolactin levels have been associated with increased breast cancer risk.
      Prolactin is essential for breast-feeding. Prolactin is lowered primarily by the
      first full-term pregnancy and not by subsequent pregnancies. The protection from
      breast cancer conferred by a long breast-feeding duration (>1 year) seems to be
      much greater for women with BRCA1 mutations (45%) than for women in the general
      population (4%). One study reported poor milk production to be more common in
      BRCA1 carriers (75%) than in non-carriers (36%). We aimed to explore the
      relationships between prolactin levels, breast-feeding duration, milk production
      and BRCA carrier status in young healthy women from high-risk breast cancer
      families. Questionnaires including information on reproductive factors and
      lifestyle were completed by 269 healthy women, aged 40 years or younger. Body
      measurements and plasma prolactin levels were obtained during cycle days 5-10 and
      18-23. Prolactin was higher in nulliparous than in parous women (P < 0.0001). In
      parous women, post-lactational prolactin levels in both cycle phases were
      significantly negatively associated with breast-feeding duration of the first
      child (P < or = 0.009), but not with additional breast-feeding of subsequent
      children (P > or = 0.12). Prolactin was higher in women who reported insufficient
      versus sufficient milk production (P < or = 0.01). Neither BRCA1/2 carrier status
      nor increasing parity was significantly associated with prolactin, breast-feeding
      duration of the first child or milk production. In conclusion, post-lactational
      prolactin levels were determined by breast-feeding duration of the first child
      and not simply by the first full-term pregnancy. Since prolactin modifies the
      risk for breast cancer, adequate counseling in favor of breast-feeding is
      essential.

PMID- 18080789
TI  - Ulcerous change decreases the accuracy of endoscopic ultrasonography diagnosis
      for the invasive depth of early gastric cancer.
AB  - BACKGROUND: With the development of endoscopic submucosal dissection, an
      expansion of the criteria for local treatment was suggested for lesions with
      ulcerous changes or undifferentiated-type adenocarcinoma. AIM OF THE STUDY: To
      determine the efficacy of endoscopic ultrasonography for such lesions, we
      retrospectively analyzed factors that influenced accurate diagnosis by endoscopic
      ultrasonography of the depth of tumor invasion. METHODS: We investigated 267
      gastric adenocarcinomas for which histopathological results were obtained by
      endoscopic mucosal resection or gastrectomy. The lesions were divided into four
      groups by histological type and the presence of ulcerous changes. Five
      clinicopathological factors were assessed for their possible associations with
      incorrect diagnosis. RESULTS: The positive predictive value (PPV) for cancer
      limited within the mucosa (endoscopic ultrasonography, EUS-M) and cancer invaded
      into the submucosal layer (EUS-SM) were 88.0% (125 of 142 lesions) and 60.0% (30
      of 50 lesions), respectively. The lesions diagnosed as EUS-M/SM borderline (37
      lesions) included 19 lesions (51.4%) of M cancer and 17 lesions (45.9%) of SM
      cancer. In logistic analysis, ulcerous changes (p < 0.0001) and macroscopic
      classification (p = 0.0284) were factors that caused incorrect diagnosis by
      endoscopic ultrasonography. In the group having differentiated-type
      adenocarcinoma with ulcerous changes, the PPV of EUS-SM was 25% (3 of 12), and
      there was a significant difference (p < 0.05) between the EUS-SM of this group
      and that of the differentiated-type adenocarcinoma without ulcerous changes.
      CONCLUSION: The accuracy of endoscopic ultrasonography tumor staging was not
      sufficient for the lesions with ulcerous changes in our study. Therefore, we
      should be careful to perform endoscopic submucosal dissection for lesions with
      ulcerous changes.

PMID- 18080790
TI  - The results of three different treatment modalities in patients with locally
      advanced nasopharyngeal carcinoma.
AB  - The aim of the study was to evaluate the toxicity and efficacy of 62 patients
      with locally advanced nasopharyngeal carcinoma (NPC) (stage III, IVA, IVB)
      treated by three different modalities. Cisplatin was given weekly 35 mg/m(2)/day
      or every 3 weeks 100 mg/m(2)/day during radiotherapy (RT) in all patients.
      Patients were classified into following three groups: The patients in the group 1
      (n=23) were treated only with concurrent chemoradiotherapy (CCRT). In the group 2
      (n=15), before the CCRT, neoadjuvant chemotherapy, consisting of intravenous
      cisplatin and docetaxel on day 1, every 3 weeks treatment cycles was
      administered. In the group 3 (n=24), adjuvant chemotherapy, consisting of
      cisplatin on day 1 and 5-fluorouracil on day 1 to 5 every 3 weeks was used after
      CCRT. Three arms were treated with the same RT technique and dose. There was no
      difference for age, sex, and stage among the groups. Radiotherapy was
      administered in planned dose for all patients. A total of 82% patients completed
      planned chemotherapy concurrent with RT. The treatment related adverse effects
      were mild or moderate in intensity. There was no statistical difference between
      the groups regarding the treatment responses. Complete response rate of RT was
      73.9%, 86.7%, and 87.5%, respectively. Median progression free survival (PFS) and
      overall survival (OS) were 13, 12, 9 months and 22, 20, 15 months for groups 1,
      2, 3, respectively. No difference was observed in median OS and PFS among three
      groups. In our study, the efficacy and toxicity of neoadjuvant and/or adjuvant
      chemotherapy with CCRT and CCRT alone were found similar.

PMID- 18080791
TI  - Perceptions about psychosis and psychiatric services: a qualitative study from
      Vellore, India.
AB  - Each culture influences the perceptions of illness and pathways to health care
      that its members follow. Non-biomedical beliefs about psychosis and treatment are
      reported from the developing world. This study explored people's perceptions on
      psychosis to understand local perceptions of the condition. Focus group
      discussions were conducted with people who have relatives with psychosis (in five
      focus groups), with members of the general public (in four focus groups), and
      with patients who had recovered from psychosis (one group) in Vellore, South
      India. These discussions were recorded, transcribed and analyzed. Participants
      recognized psychosis as an illness category, and viewed indigenous healing
      methods as complementary to allopathic treatments. Multiple and apparently
      contradictory beliefs on different aspects of psychosis were often simultaneously
      held by participants. People in the community were more likely to express
      negative views about mental illness. Relatives of patients with psychosis wanted
      more support from mental health professionals and community in combating stigma
      against mental illness. Results of this study reveal the complex nature of
      illness perspectives among patients with psychosis, their relatives and
      community. Bio-medical and indigenous beliefs are simultaneously held by a
      significant number of people who often seek help from both modern and traditional
      health systems at the same time. The results indicate the need for better
      understanding of local perceptions of psychosis.

PMID- 18080792
TI  - Gender differences in the associations between past-year gambling problems and
      psychiatric disorders.
AB  - BACKGROUND: Psychiatric disorders frequently co-occur with pathological gambling.
      The extent to which co-occurence extends to subsyndromal levels of gambling or
      differs between women and men is incompletely understood. AIM: To examine whether
      the association between psychiatric disorders and past-year gambling problems is
      stronger in women than men. METHODS: Data from the national epidemiological
      survey of alcoholism and related disorders (NESARC) (n = 43,093) were analyzed.
      RESULTS: Increasing severity of past-year gambling problems was associated with
      increasing odds of most past-year Axis I and lifetime Axis II disorders,
      regardless of gender. Associations between gambling problems and major
      depression, dysthymia, panic disorder, and nicotine dependence were statistically
      stronger in women than in men. CONCLUSIONS: A severity-related association exists
      between past-year gambling problems and psychiatric disorders. The stronger
      associations in women suggest that gambling research, prevention and treatment
      efforts consider gender differences.

PMID- 18080793
TI  - Relationship between mandibular inferior cortex and general bone metabolism in
      older adults.
AB  - The purpose of this study was to investigate whether a link exists between the
      jawbone and general bone metabolism. The results of our study indicate that a
      mandibular inferior cortical erosion finding on dental panoramic radiographs is
      significantly associated with increased biochemical markers of bone turnover.
      INTRODUCTION: The purpose of this study was to investigate whether a link exists
      between the jawbone and general bone metabolism. METHODS: We measured values of
      serum bone-specific alkaline phosphatase (S-BAP) and urinary N-telopeptide cross
      links of type I collagen (U-NTX). To evaluate the jawbone, we used mandibular
      inferior cortex (MIC) classification on dental panoramic radiographs. After 134
      subjects were divided into three groups (C1: normal cortex, C2: mildly to
      moderately eroded cortex, C3: severely eroded cortex), we evaluated the
      relationship between S-BAP or U-NTX and MIC classification by Scheffe's multiple
      comparison test. RESULTS: A significant correlation was found between MIC
      classification and S-BAP (C1 vs. C2: p < 0.01, C1 vs. C3: p < 0.01, C2 vs. C3:
      NS). A significant correlation was found between MIC classification and U-NTX (C1
      vs. C2: p < 0.01, C1 vs. C3: p < 0.001, C2 vs. C3: p < 0.01). CONCLUSIONS: The
      results of our study indicate that the mandibular inferior cortical erosion
      finding on dental panoramic radiographs is significantly associated with
      increased S-BAP and U-NTX levels. We suggest that there is an association between
      the jawbone and general bone metabolism.

PMID- 18080794
TI  - Metal concentrations of common freshwater and marine fish from the Pearl River
      Delta, south China.
AB  - Sediments and fish, including tilapia (Oreochromis mossambicus), bighead carp
      (Aristichthys nobilis), grass carp (Ctenopharyngodon idellus), and mandarin fish
      (Siniperca chuatsi) were collected from different fish ponds in the Pearl River
      Delta (Tanzhou, Sanjiao, Guangzhou, Shipai, Changan, and Mai Po) for the analysis
      of metalloids and heavy metals [arsenic (As), cadmium (Cd), chromium (Cr),
      mercury (Hg), and lead (Pb)]. The pollution of As in pond sediments was great;
      however, As in the edible parts of pond fish were within the international
      permissible safety levels for human consumption. Axial muscles from 10 species
      each of freshwater and marine fish purchased from markets in Hong Kong were also
      analyzed for As, Cd, Cr, Cu, Hg, Ni, Pb and Zn. Freshwater fish contained 0.24 to
      2.13 mg/kg As, 0.10 to 0.17 mg/kg Cd, 0.09 to 0.36 mg/kg Cr, 0.06 to 0.35 mg/kg
      Cu, 0.07 to 0.34 mg/kg Hg, 0.04 to 0.36 mg/kg Ni, 0.11 to 0.52 mg/kg Pb, and 2.67
      to 19.1 mg/kg Zn (wet weight). Marine fish had higher Hg and lower Pb
      concentrations than freshwater fish. A few fish species had average
      concentrations greater than the international standards for Cd and Pb established
      by the European Union and the China National Standard Management Department.
      Total Hg concentrations in 10 of 20 market fish species were generally greater
      than those of the World Health Organization's recommended limit of 0.2 mg/kg for
      at-risk groups, such as children and pregnant women. Daily intake through fish
      consumption of these metals were compared with the Provisional Tolerable Weekly
      Intake proposed by the Joint Food and Agriculture Organization/World Health
      Organization Expert Committee on Food Additives. There appears to be potential
      threat to local people from Hg contamination because of the high marine fish
      consumption rate (142 g/d/person).

PMID- 18080795
TI  - Grouping lakes for water quality assessment and monitoring: the roles of
      regionalization and spatial scale.
AB  - Regionalization frameworks cluster geographic data to create contiguous regions
      of similar climate, geology and hydrology by delineating land into discrete
      regions, such as ecoregions or watersheds, often at several spatial scales.
      Although most regionalization schemes were not originally designed for aquatic
      ecosystem classification or management, they are often used for such purposes,
      with surprisingly few explicit tests of the relative ability of different
      regionalization frameworks to group lakes for water quality monitoring and
      assessment. We examined which of 11 different lake grouping schemes at two
      spatial scales best captures the maximum amount of variation in water quality
      among regions for total nutrients, water clarity, chlorophyll, overall trophic
      state, and alkalinity in 479 lakes in Michigan (USA). We conducted analyses on
      two data sets: one that included all lakes and one that included only minimally
      disturbed lakes. Using hierarchical linear models that partitioned total variance
      into within-region and among-region components, we found that ecological drainage
      units and 8-digit hydrologic units most consistently captured among-region
      heterogeneity at their respective spatial scales using all lakes (variation among
      lake groups = 3% to 50% and 12% to 52%, respectively). However, regionalization
      schemes capture less among-region variance for minimally disturbed lakes.
      Diagnostics of spatial autocorrelation provided insight into the relative
      performance of regionalization frameworks but also demonstrated that region size
      is only partly responsible for capturing variation among lakes. These results
      suggest that regionalization schemes can provide useful frameworks for lake water
      quality assessment and monitoring but that we must identify the appropriate
      spatial scale for the questions being asked, the type of management applied, and
      the metrics being assessed.

PMID- 18080796
TI  - Low genetic variability in the coat and movement proteins of American plum line
      pattern virus isolates from different geographic origins.
AB  - Until very recently isolates of American plum line pattern virus (APLPV) had not
      been reported from outside North America. The nucleotide sequences corresponding
      to the movement (MP) and coat (CP) proteins of eight APLPV isolates from five
      Mediterranean countries were determined. Sequence analysis showed that both MP
      and CP genes are highly conserved irrespective of geographic origin. The study of
      the distribution of synonymous and nonsynonymous changes along both open reading
      frames revealed that these proteins are under the effect of negative purifying
      selection. The MP and CP of APLPV possess most of the functional motifs described
      for other members of the genus Ilarvirus.

PMID- 18080797
TI  - Increased yield of porcine circovirus-2 by a combined treatment of PK-15 cells
      with interferon-gamma and inhibitors of endosomal-lysosomal system acidification.
AB  - Treatment of porcine kidney (PK-15) cells with either interferon-gamma (IFN
      gamma) or endosomal- lysosomal system acidification inhibitors increases
      replication of porcine circovirus type 2 (PCV2). In the present study, the effect
      of a combination of these treatments on the number of infected cells and virus
      yield was tested. The number of PCV2 (Stoon-1010)-infected PK-15 cells increased
      in cells treated with ammonium chloride (445 +/- 39% increase), IFN-gamma (446 +/
      8%), ammonium chloride + IFN-gamma (1721 +/- 283%), chloroquine diphosphate
      (1037 +/- 121%), chloroquine diphosphate + IFN-gamma (2199 +/- 255%), monensin
      (950 +/- 178%) and monensin + IFN-gamma (1948 +/- 60%). Combined IFN-gamma and
      endosomal-lysosomal system acidification inhibitors increased PCV2 yield by up to
      50 times compared to untreated PK-15. This augmented virus replication in PK-15
      cells may be helpful in the production of PCV2 vaccines.

PMID- 18080798
TI  - Elevated levels of interleukin-2 receptor and intercellular adhesion molecule 1
      in sera from a venezuelan cohort of patients with dengue.
AB  - This study evaluated the levels of soluble interleukin-2 receptor (sIL-2R) and
      soluble intercellular adhesion molecule-1 (sICAM-1) in patients with dengue. Sera
      from 17 patients with dengue fever (DF), 15 with dengue hemorrhagic fever (DHF)
      and 12 healthy individuals were obtained. Increased levels of sIL-2R and sICAM-1
      were found in patients with DF and DHF when compared to normal; those were not
      correlated with leukocytes, hepatic serum enzyme levels or haemostatic
      parameters. Levels of sIL-2R were related to the different grades of DHF. These
      results suggest that increased levels of sIL-2R and sICAM-1 are a common feature
      of dengue.

PMID- 18080799
TI  - Bleeding after antithrombotic therapy in patients with acute ischemic heart
      disease: is it the drugs or how we use them?
AB  - Definitions of bleeding must be considered when evaluating results of clinical
      trials. Assessments of bleeding impact based on clinical criteria may be more
      relevant to patient outcomes than those based on simple laboratory measures like
      an isolated change in hemoglobin, that do not appear to affect patient care. The
      risk of excessive bleeding in patients who receive antiplatelet and
      antithrombotic therapy is related to a combination of patient characteristics
      (older age, female sex, impaired renal function), and delivery factors (excessive
      dosing, stacking of anticoagulants). Investigators should justify components of
      bleeding endpoints as being clinically meaningful, sufficiently frequent in the
      study population, and affected by the intervention.

PMID- 18080800
TI  - Soluble P-selectin and vascular endothelial growth factor in steady state sickle
      cell disease: relationship to genotype.
AB  - Sickle cell disease (SCD) is characterised by abnormal coagulopathy and
      angiogenesis although their relationships in two common genotypes, homozygous
      (HbSS) SCD and sickle-haemoglobin C disease (HbSC), are unexplored. We measured
      markers of platelet activation (soluble P-selectin [sP-selectin]), fibrinolysis
      (D-dimer) and angiogenesis (vascular endothelial growth factor [VEGF]) in 27 HbSS
      patients, 37 HbSC patients and in 42 age and race matched subjects with normal
      haemoglobin (AA). sP-selectin (P = 0.025) and D-dimers (P < 0.001) were higher in
      HbSS than in HbSC but there was no difference in VEGF. In HbSC, sPselectin
      correlated with VEGF (P = 0.012) and D-dimers (P = 0.021). There were no
      significant correlations in health or in HbSS. Platelet and coagulation
      activation, but not angiogenic activity, is elevated in HbSS disease compared to
      the clinically milder HbSC genotype. The correlation between sP-selectin and VEGF
      in SCD and HbSC disease is consistent with the view that VEGF is released from
      platelets during in vivo activation.

PMID- 18080801
TI  - Physical properties of two types of calcium stores and SERCAs in human platelets.
AB  - The aim of this work was to obtain experimental data depending on the properties
      of calcium stores and SERCAs, to analyse these data in terms of the models based
      on simulation of the cellular compartments as communicating vessels, and to
      relate this way the data to the above properties. The main characteristics of the
      stores and corresponding SERCAs have been estimated. Calcium content in the DTS
      is approximately 1.5 x 10(6) ions per cell, that in the acidic stores,
      approximately 0.64 x 10(6) ions per cell. The rate constant of background calcium
      leakage from the DTS is approximately 0.0033 s(-1), that from the acidic stores,
      approximately 0.1 s(-1). The background activity of SERCA2b is approximately 0.22
      x 10(6 )s(-1) ions per cell, that of SERCA3, approximately 2.5 x 10(6 )s(-1) ions
      per cell. The properties of both calcium stores and the SERCAs and the
      characteristics found might be related to physiological or pathological state of
      the cells.

PMID- 18080802
TI  - External Qi of Yan Xin Qigong induces G2/M arrest and apoptosis of androgen
      independent prostate cancer cells by inhibiting Akt and NF-kappa B pathways.
AB  - Long-term clinical observations and ongoing studies have shown antitumor effects
      of external Qi of Yan Xin Qigong (YXQG-EQ) that originated from traditional
      Chinese medicine (TCM). In order to understand the molecular mechanisms
      underlying the antitumor effects of YXQG-EQ, we investigate the effects of YXQG
      EQ on growth and apoptosis in androgen-independent prostate cancer PC3 cells. We
      found that exposure to YXQG-EQ led to G2/M arrest associated with reduced cyclin
      B1 expression and apoptosis in PC3 cells. YXQG-EQ treatment inhibited
      constitutive and epidermal growth factor-induced Akt phosphorylation, basal and
      TNF-alpha-induced NF-kappaB activation, and downregulated anti-apoptotic Bcl-2
      and Bcl-xL expression. In contrast, exposure to YXQG-EQ increased phosphorylation
      of Akt and Erk1/2 in human umbilical vein endothelial cells (HUVEC), and had no
      cytotoxic effect on either HUVEC or peripheral blood mononuclear cells (PBMC).
      These results indicate that YXQG-EQ has profound effects on growth and apoptosis
      of prostate cancer cells by targeting survival pathways including the Akt and NF
      kappa B pathways.

PMID- 18080803
TI  - IKK gamma (NEMO) is involved in the coordination of the AP-1 and NF-kappa B
      pathways.
AB  - Tumor necrosis factor alpha (TNF alpha) activates the nuclear factor-kappaB (NF
      kappa B) pathway in various cell types, leading to expression of cell survival
      and inflammatory proteins. One mechanism of cell survival brought about by NF
      kappa B is the inhibition of Activator Protein-1 (AP-1), which when activated,
      could lead to cell death. However, TNFalpha can also induce the AP-1 pathway, and
      the mechanisms by which these two pathways are regulated in response to TNF alpha
      are poorly understood. We proposed that Inhibitor of kappa B Kinase gamma (IKK
      gamma) (which is also known as NF-kappa B essential modulator, NEMO) plays a key
      role in integrating and coordinating these two pathways. Our results showed that
      IKK gamma activates the AP-1 pathway, via a mechanism that is dependent on the
      first leucine zipper (LZ) domain of IKK gamma, by interacting with two proteins
      of the AP-1 complex, c-Jun and c-Fos, and changing the phosphorylation status of
      c-Jun. Even though IKK gamma is required for the activation of NF-kappa B, we
      found that it reduced the activity of NF-kappa B when it was overexpressed. In
      summary, we demonstrated that transfected IKK gamma, while inhibiting the NF
      kappa B pathway, directly interacts with the AP-1 proteins and activates the AP-1
      pathway independent of its effects on NF-kappa B. Our results indicate that IKK
      gamma regulates TNF alpha signaling by coordinating cell responses mediated by
      the AP-1 and NF-kappa B pathways.

PMID- 18080805
TI  - Racial and ethnic disparities in the treatment of cerebrovascular diseases:
      importance to the practicing neurosurgeon.
AB  - OBJECTIVES: In various surgical procedures, evidence for racial/ethnic
      disparities has continued to grow in recent years. Our purpose was to review the
      current literature regarding racial/ethnic disparities in the United States in
      the surgical treatment and outcome of three different cerebrovascular disease
      entities: carotid stenosis, intracranial aneurysm, and cerebral arteriovenous
      malformation (AVM). METHODS: We conducted an electronic search of literature
      published between January 1, 1966 and December 10, 2005 using MEDLINE (OVID),
      EMBASE, CINAHL, and Science Citation Index (Web of Science), along with manual
      reference checking, resulting in 313 screened items. Main outcome measures
      examined were racial/ethnic differences in procedure utilization rates and
      perioperative stroke, death, and complications. RESULTS: Out of 3,624,581
      articles indexed in MEDLINE pertaining to the treatment of these 3
      cerebrovascular diseases, 141 (0.004%) articles pertained to minority groups and
      33 (0.001%) articles met search criteria for inclusion in this review. Two
      additional articles were found in other searched databases. Carotid
      endarterectomy was the focus of 30 articles, and 5 articles pertained to
      craniotomy for treatment of intracranial aneurysms. No articles were found that
      examined racial differences in AVM treatment. Our systematic review found
      evidence of racial disparities in the surgical treatment of patients with carotid
      stenosis and aneurysmal subarachnoid hemorrhage. The data, however, is limited
      and confounded. CONCLUSION: Results of this comprehensive literature review
      suggest that racial disparities in cerebrovascular disease are understudied. Race
      associated differences in neurosurgical outcomes must be documented and
      vigorously investigated to determine the basis of any observed differences and
      ensure that we are providing the best care possible to all of our patients.

PMID- 18080804
TI  - A gain-of-function mutation of transcriptional factor PTL results in curly
      leaves, dwarfism and male sterility by affecting auxin homeostasis.
AB  - GT factors are plant-specific trihelix DNA-binding transcription factors, which
      are involved in light responses and other developmental processes in plant. We
      identified a gain-of-function mutant of a GT-2 factor gene, PETAL LOSS (PTL),
      which displayed pleiotropic phenotypes including dwarfism, curly leaves, retarded
      growth and male sterility. We found that constitutive and ectopic over-expression
      of PTL driven by the CaMV 35S promoter could not recapitulate the phenotypes of
      the 35S enhancer-driven mutant ptl-D, and was lethal in some of the transgenic
      plants at the cotyledon developmental stage, suggesting that accurate temporal
      and spatial expression of PTL is essential for its proper functional
      implementation during plant development. Further analysis showed that ptl-D was
      defective in auxin action and that the alteration of auxin distribution
      corresponded to the curly leaf phenotype. The fact that degeneration of septum
      cells and subsequent breakage along the stomium was not observed in ptl-D anthers
      suggests that defective anther dehiscence was the cause for male sterility.
      Identification and characterization of the gain-of-function mutant ptl-D will
      improve our understanding of the diverse functions of GT factors during plant
      development.

PMID- 18080806
TI  - The value of CT angiography and transcranial doppler sonography in triaging
      suspected cerebral vasospasm in SAH prior to endovascular therapy.
AB  - BACKGROUND: Transcranial Doppler sonography (TCD) is a noninvasive method for
      detecting arterial cerebral vasospasm (CVS) in aneurysmal subarachnoid hemorrhage
      (SAH). Computed tomographic angiography (CTA) has been increasingly used for CVS
      diagnosis. The purpose of this study was to evaluate the degree of agreement
      between TCD and CTA in diagnosing clinical CVS following SAH, and to define the
      role of CTA in triaging patients prior to digital subtraction angiography (DSA)
      and endovascular intervention. METHODS: Fifty-five consecutive patients with
      aneurysmal SAH who underwent sequential TCD and CTA were analyzed. TCD CVS was
      defined as anterior circulation peak mean velocity (PMV) >160 cm/s, basilar
      artery (BA) PMV >90 cm/s, and Lindegaard ratio (LR) >6. CTA CVS was defined as
      >50% luminal narrowing in the affected vessel. Clinical CVS was defined as the
      onset of new focal neurological deficit attributed to delayed ischemic injury.
      RESULTS: Thirteen patients (24%) had clinical CVS and 42 patients (76%) were
      asymptomatic. All patients with clinical CVS had also radiological evidence of
      CVS (agreement 100%). In 35 patients without clinical CVS, both tests agreed for
      absence of CVS in 28 cases (agreement 83%). The remaining 7 asymptomatic patients
      had radiological CVS only, in disagreement with clinical absence of CVS (17%).
      CONCLUSIONS: Clinical evaluation and TCD can reliably diagnose CVS in symptomatic
      patients and PMV >180 cm/s, or can rule out CVS in asymptomatic patients with PMV
      <140 cm/s. In this category of patients, adding a CTA to clinical evaluation and
      TCD may not be warranted.

PMID- 18080807
TI  - Amplification of acute focal ischemic deficit by narcotics.
AB  - INTRODUCTION: This article describes two patients with major ischemic stroke
      symptoms who had extremely small areas of acute brain infarction, suggestive of
      acute intrahemispheric diaschisis. Both patients were using narcotic analgesics
      during their stroke, and in both cases the clinical deficits improved
      dramatically with naloxone. DISCUSSION: We postulate that the narcotics amplified
      the ischemic stroke symptoms and that this effect was antagonized by naloxone.
      CONCLUSION: This suggests that the opiate system may be involved in the process
      of intrahemispheric diaschisis.

PMID- 18080808
TI  - Mineral chaperones: a role for fetuin-A and osteopontin in the inhibition and
      regression of pathologic calcification.
AB  - Clinical nephrologists are well aware of the consequences of pathologic
      mineralization (calcification). Several studies have found a strong association
      between vascular and valvular mineralization and advanced or end-stage chronic
      kidney disease (CKD), with shorter survival times and increased morbidity. In the
      cardiology community, until quite recently, ectopic mineralization was considered
      harmless or even beneficial. Some still assume that atherosclerotic intima
      mineralization stabilizes atherosclerotic plaques, thus doing more good than
      harm. We suggest that vascular mineralization and indeed soft tissue
      mineralization in general may be a way in which the body deals with certain
      adverse situations involving local inflammation, associated tissue damage and
      tissue remodeling. Ectopic soft tissue mineralization resembles physiological
      bone mineralization in many ways. Markers of mineralizing bone also are present
      during soft tissue mineralization. We postulate that it may be possible to
      reverse soft tissue mineralization by applying selected principles of bone
      catabolism, namely mineral dissolution and phagocytosis. We consider putative
      strategies for therapeutic intervention to maximize the clearing of calcified
      debris particles. In particular, we discuss the roles of the plasma protein
      fetuin-A/alpha2HS-glycoprotein and the mineral-binding protein osteopontin in the
      prevention and possible regression of mineralization in disease.

PMID- 18080809
TI  - Comparative analysis of inbred and hybrid maize at the diploid and tetraploid
      levels.
AB  - Heterosis often occurs in offspring derived from a cross between inbred or
      divergent parents and can be observed as the superior performance of these
      hybrids for a wide variety of characters. Heterosis was compared in maize lines
      at two ploidy levels, diploid and tetraploid, to gain a better understanding of
      the interaction of heterosis and ploidy level. Employing genetically identical
      diploid and tetraploid maize derived from four different inbred lines, we
      investigated heterosis for 11 morphological traits, including several plant
      height measures, as well as flowering time for both silks and anthers. We find
      that the heterotic response of a certain hybrid differs between diploid and
      tetraploid lines, and that the response at one ploidy cannot serve as a predictor
      for the other. Also, progressive heterosis was found for several of the
      characters in the tetraploid double-cross hybrid, which can have four different
      alleles at one locus, compared to the double-cross diploid hybrids, which can
      only possess two alleles per locus. Overall, the results indicate that the
      heterotic response of tetraploid maize lines differs significantly from that of
      the diploid.

PMID- 18080810
TI  - Mediation of beta-endorphin in andrographolide-induced plasma glucose-lowering
      action in type I diabetes-like animals.
AB  - In the present study, we investigated the mechanism(s) for glucose-lowering
      action of andrographolide in streptozotocin-induced diabetic rats (STZ-diabetic
      rats). Andrographolide lowered plasma glucose concentrations in a dose-dependent
      manner and increased plasma beta-endorphin-like immunoreactivity (BER) dose
      dependently in diabetic rats. Both of these responses to andrographolide were
      abolished by the pretreatment of animals with prazosin or N-(2-(2
      cyclopropylmethoxy) ethyl) 5-choro-alpha-dimethyl-1H-indole-3-thylamine (RS17053)
      at doses sufficient to block alpha1-adrenoceptors (ARs). Also, andrographolide
      enhanced BER release from isolated rat adrenal medulla in a concentration-related
      manner that could be abolished by alpha1-ARs antagonists. Bilateral adrenalectomy
      in STZ-diabetic rats eliminated the activities of andrographolide, including the
      plasma glucose-lowering effect and the plasma BER-elevating effect.
      Andrographolide failed to lower plasma glucose in the presence of opioid micro
      receptor antagonists and in the opioid micro-receptor knockout diabetic mice.
      Treatment of STZ-diabetic rats with andrographolide resulted in the reduced
      expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver and an increased
      expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle. These
      effects were also blocked by opioid micro-receptor antagonists. In conclusion,
      our results suggest that andrographolide may activate alpha1-ARs to enhance the
      secretion of beta-endorphin which can stimulate the opioid micro-receptors to
      reduce hepatic gluconeogenesis and to enhance the glucose uptake in soleus
      muscle, resulting in a decrease of plasma glucose in STZ-diabetic rats. However,
      the roles of other endogenous opioid peptides or the mixture of several opioid
      peptides in the activation of opioid micro-receptors associated with the plasma
      glucose-lowering action of andrographolide, should be considered and need more
      investigation in the future.

PMID- 18080811
TI  - Development of electrochemical biosensors based on sol-gel enzyme encapsulation
      and protective polymer membranes.
AB  - Protective polymer coatings have been used to enhance the retention of enzymes in
      sol-gel films as immobilisation phases in electrochemical biosensors. Carbon film
      electrodes were electrochemically modified with poly(neutral red) (PNR). These
      electrodes were coated with oxysilane sol-gels incorporating glucose oxidase and
      an outer coating of carboxylated PVC (CPVC) or polyurethane (PU), with and
      without Aliquat-336 or isopropyl myristate (IPM) plasticizer, was applied. The
      biosensors were characterised electrochemically using cyclic voltammetry and
      amperometry, electrochemical impedance spectroscopy and scanning electron
      microscopy. Impedance spectra showed that the electrode surface is most active
      when the sol-gel-GOx layer is not covered with a membrane. However, membranes
      without plasticizer extend the lifetime of the biosensor to more than 2 months
      when PU is used as an outer membrane. The linear range of the biosensors was
      found to be 0.05-0.50 mM of glucose and the biosensor with PU outer membrane
      exhibited higher sensitivity (ca.117 nA mM(-1)) in the region of linear response
      than that with CPVC. The biosensors were applied to glucose measurement in
      natural samples of commercial orange juice.

PMID- 18080812
TI  - The association of ABCB1 polymorphisms and elevated serum digitoxin
      concentrations in geriatric patients.
AB  - OBJECTIVE: Digitoxin is a known substrate of the efflux pump P-glycoprotein (gene
      name: ABCB1). P-glycoprotein expression was shown to be modulated by single
      nucleotide polymorphisms in the ABCB1 gene, but it remains unclear whether these
      polymorphisms influence digitoxin blood levels. Our objective was to examine the
      association of ABCB1 C3435T genotype and elevated serum digitoxin concentrations
      (SDC) in a cohort of 77 geriatric patients consecutively admitted to a geriatric
      department over a 12-month period. METHODS: The impact of ABCB1 3435 CC, CT, and
      TT genotypes on SDC and SDC normalized for daily digitoxin dosage and body weight
      was assessed by multivariate regression analysis. RESULTS: Among participants, 18
      (23%) had the CC, 36 (47%) the CT, and 23 (30%) the TT genotype. Adjusting for
      relevant covariates, no significant association of ABCB1 C3435T genotype and SDC
      or normalized SDC was detected. Mean SDC was 22.4 ng/ml (95% CI 18.9-25.9) for
      the TT, 21.8 ng/ml (95% CI 18.1-25.5) for the CT, and 25.7 ng/ml (95% CI 20.6
      30.8) for the CC genotype. The means for normalized SDC were 5.2 kg.l(-1) (95% CI
      4.3-6.1) for the TT, 6.1 kg.l(-1) (95% CI 4.7-7.5) for the CT, and 6.2 kg.l(-1)
      (95% CI 4.6-7.7) for the CC genotype. CONCLUSION: In this sample of frail
      geriatric patients, the impact of ABCB1 C3435T genotype on serum digitoxin
      concentration was not of major relevance. Regular monitoring of digitoxin blood
      levels and surveillance of appropriate drug use remain the best ways to prevent
      digitoxin intoxications in the elderly.

PMID- 18080813
TI  - Metabolic engineering of Escherichia coli to enhance phenylalanine production.
AB  - The global regulatory system of Escherichia coli, carbon storage regulator (Csr),
      was engineered to increase the intracellular concentration of
      phosphoenolpyruvate. We examined the effects of csrA and csrD mutations and csrB
      overexpression on phenylalanine production in E. coli NST37 (NST). Overexpression
      of csrB led to significantly greater phenylalanine production than csrA and csrD
      mutations (2.33 vs 1.67 and 1.61 g l(-1), respectively; P < 0.01). Furthermore,
      the overexpression of csrB was confirmed by the observed increase in csrB
      transcription level. We also determined the effect of overexpressing
      transketolase A (TktA) or glucose-6-phosphate dehydrogenase (Zwf) in NST and the
      csrA mutant of NST (NSTCSRA) on phenylalanine production. The NSTCSRA strain
      overexpressing TktA (NSTCSRA [pTktA]) produced significantly more phenylalanine
      than that of Zwf (2.39 vs 1.61 g l(-1); P > 0.01). Furthermore, we examined the
      effect of overexpressing TktA, 3-deoxy-D: -arabino-heptulosonate-7-phosphate
      synthase (AroF(FR)), and chorismate mutase/prephenate dehydratase (PheA(FR))
      together in NSTCSRA (NSTCSRA [pTkaFpA]). It is interesting to note that NSTCSRA
      [pTkaFpA] produced significantly less phenylalanine than both NSTCSRA [pTktA] and
      NST overexpressing csrB (NST [pCsrB]) (1.84 vs 2.39 and 2.33 g l(-1),
      respectively; P < 0.01). Thus, csrB overexpression or csrA mutation in
      combination with tktA overexpression was more effective than previous approaches
      that targeted the glycolytic or aromatic pathway enzymes for enhancing
      phenylalanine production.

PMID- 18080814
TI  - A thermoactive glucoamylase with biotechnological relevance from the
      thermoacidophilic Euryarchaeon Thermoplasma acidophilum.
AB  - A gene encoding an intracellular glucoamylase was identified in the genome of the
      extreme thermoacidophilic Archaeon Thermoplasma acidophilum. The gene taGA,
      consisting of 1,911 bp, was cloned and successfully expressed in Escherichia
      coli. The recombinant protein was purified 22-fold to homogeneity using heat
      treatment, anion-exchange chromatography, and gel filtration. Detailed analysis
      shows that the glucoamylase, with a molecular weight of 66 kDa per subunit, is a
      homodimer in its active state. Amylolytic activity was measured over a wide range
      of temperature (40-90 degrees C) and pH (pH 3.5-7) and was maximal at 75 degrees
      C and at acidic condition (pH 5). The recombinant archaeal glucoamylase uses a
      variety of polysaccharides as substrate, including glycogen and amylose. Maximal
      activity was measured towards amylopectin with a specific activity of 4.2 U/mg
      and increased almost threefold in the presence of manganese. Calcium ions have a
      pronounced effect on enzyme stability; in the presence of 5 mM CaCl(2), the half
      life increased from 15 min to 2 h at 80 degrees C.

PMID- 18080816
TI  - Graph decompositions for demographic loop analysis.
AB  - A new approach to loop analysis is presented in which decompositions of the total
      elasticity of a population projection matrix over a set of life history pathways
      are obtained as solutions of a constrained system of linear equations. In loop
      analysis, life history pathways are represented by loops in the life cycle graph,
      and the elasticity of the loop is interpreted as a measure of the contribution of
      the life history pathway to the population growth rate. Associated with the life
      cycle graph is a vector space -- the cycle space of the graph -- which is spanned
      by the loops. The elasticities of the transitions in the life cycle graph can be
      represented by a vector in the cycle space, and a loop decomposition of the life
      cycle graph is then defined to be any nonnegative linear combination of the loops
      which sum to the vector of elasticities. In contrast to previously published
      algorithms for carrying out loop analysis, we show that a given life cycle graph
      admits of either a unique loop decomposition or an infinite set of loop
      decompositions which can be characterized as a bounded convex set of nonnegative
      vectors. Using this approach, loop decompositions which minimize or maximize a
      linear objective function can be obtained as solutions of a linear programming
      problem, allowing us to place lower and upper bounds on the contributions of life
      history pathways to the population growth rate. Another consequence of our
      approach to loop analysis is that it allows us to identify the exact tradeoffs in
      contributions to the population growth rate that must exist between life history
      pathways.

PMID- 18080815
TI  - Quinolinic acid induced neurodegeneration in the striatum: a combined in vivo and
      in vitro analysis of receptor changes and microglia activation.
AB  - PURPOSE: Huntington's disease (HD) is a progressive neurodegenerative disorder,
      which is characterised by prominent neuronal cell loss in the basal ganglia with
      motor and cognitive disturbances. One of the most well-studied pharmacological
      models of HD is produced by local injection in the rat brain striatum of the
      excitotoxin quinolinic acid (QA), which produces many of the distinctive features
      of this human neurodegenerative disorder. Here, we report a detailed analysis,
      obtained both in vivo and in vitro of this pharmacological model of HD. MATERIALS
      AND METHODS: By combining emission tomography (PET) with autoradiographic and
      immunocytochemical confocal laser techniques, we quantified in the QA-injected
      striatum the temporal behavior (from 1 to 60 days from the excitotoxic insult) of
      neuronal cell density and receptor availability (adenosine A(2A) and dopamine
      D(2) receptors) together with the degree of microglia activation. RESULTS: Both
      approaches showed a loss of adenosine A(2A) and dopamine D(2) receptors
      paralleled by an increase of microglial activation. CONCLUSION: This combined
      longitudinal analysis of the disease progression, which suggested an impairment
      of neurotransmission, neuronal integrity and a reversible activation of brain
      inflammatory processes, might represent a more quantitative approach to compare
      the differential effects of treatments in slowing down or reversing HD in rodent
      models with potential applications to human patients.

PMID- 18080818
TI  - Temperature rise during polymerization of three different provisional materials.
AB  - The purpose of this study was to evaluate the temperature rise during
      polymerization of three different provisional materials by direct method on two
      different dentin disc thicknesses. Two autopolymerizing; bis-acrylic composite
      (Fill-in; Kerr), polymethyl methacrylate (Temdent; Weil Dental), and one light
      polymerizing composite (Revotek LC; GC) provisional restoration materials were
      used in this study. Sixty dentin discs were prepared from extracted molars
      (diameter, 5 mm; height, 1 or 2 mm). These dentin discs (1 or 2 mm) were placed
      on apparatus developed to measure temperature rise. The temperature rise during
      polymerization was measured under the dentin disc with a J-type thermocouple wire
      that was connected to a data logger. Statistical analysis was performed with two
      way analysis of variance followed by Tukey HSD test (alpha=0.05). Temperature
      rise values statistically varied according to the provisional restoration
      material used (light polymerized, auto polymerized; P<0.001) and the dentin
      thickness (1 and 2 mm; P<0.001). The polymethyl methacrylate based provisional
      material induced significantly higher temperature rise than other provisional
      restoration materials at 2-mm dentin thickness (P<0.01). At 1-mm dentin
      thickness, polymethyl methacrylate and composite induced significantly higher
      temperature increase than bis-acrylic composite provisional material (P<0.05).
      The risk for heat-induced pulpal damage should be taken into consideration during
      polymerization of provisional materials in deep cavities in which dentin
      thickness is less than 1 mm.

PMID- 18080817
TI  - AFM as a tool to probe and manipulate cellular processes.
AB  - The exploration of molecular processes governing physiological functions has
      significantly benefited from the emergence of novel nanoscaled techniques. Atomic
      force microscopy in force measurement mode can be used to investigate a multitude
      of cellular events in individual living cells with great sensitivity. Precise
      regions of the plasma membrane can be examined in relation to particular
      signalling pathways activated by a mechanical stimulus. Similarly, subtle
      cellular movements induced by biochemical activation of specific membrane
      receptors can be detected in real time with excellent temporal and spatial
      resolution. The possibility to challenge locally and mechanically cell surface
      receptors also provides information on the control exerted by a cell over
      individual adhesion sites. Overall, this information is vital for an in-depth
      understanding of mechanisms related to cellular movement and morphological
      regulation. Lastly, atomic force microscope-based nanomanipulations on living
      cells have recently been proposed as a tool to influence and monitor cellular
      homeostasis by introducing specific molecular entities into or extracting them
      from the cytoplasm of individual cells. This review provides detailed examples on
      how such atomic force microscopy experiments can be conducted to investigate
      processes relevant to cell physiology.

PMID- 18080819
TI  - Magnetic resonance elastography compared with rotational rheometry for in vitro
      brain tissue viscoelasticity measurement.
AB  - Magnetic resonance elastography (MRE) is an increasingly used method for non
      invasive determination of tissue stiffness. MRE has shown its ability to measure
      in vivo elasticity or viscoelasticity depending on the chosen rheological model.
      However, few data exist on quantitative comparison of MRE with reference
      mechanical measurement techniques. MRE has only been validated on soft
      homogeneous gels under both Hookean elasticity and linear viscoelasticity
      assumptions, but comparison studies are lacking concerning viscoelastic
      properties of complex heterogeneous tissues. In this context, the present study
      aims at comparing an MRE-based method combined with a wave equation inversion
      algorithm to rotational rheometry. For this purpose, experiments are performed on
      in vitro porcine brain tissue. The dynamic behavior of shear storage (G') and
      loss (G ('')) moduli obtained by both rheometry and MRE at different frequency
      ranges is similar to that of linear viscoelastic properties of brain tissue found
      in other studies. This continuity between rheometry and MRE results consolidates
      the quantitative nature of values found by MRE in terms of viscoelastic
      parameters of soft heterogeneous tissues. Based on these results, the limits of
      MRE in terms of frequency range are also discussed.

PMID- 18080821
TI  - Idiopathic dilatation of the right atrium in a female adult.

PMID- 18080820
TI  - Chloroquine retinopathy: lipofuscin- and melanin-related fundus autofluorescence,
      optical coherence tomography and multifocal electroretinography.
AB  - PURPOSE: To evaluate melanin-related near-infrared fundus autofluorescence (NIA,
      excitation 787 nm, emission > 800 nm), lipofuscin-related fundus autofluorescence
      (FAF, excitation 488 nm, emission >500 nm), optical coherence tomography (OCT),
      and multifocal electroretinography (mfERG) in patients with chloroquine (CQ)
      retinopathy. METHODS: Two patients with progressed CQ retinopathy underwent
      clinical examination, ISCEV mfERG evaluation, and FAF and NIA imaging using a
      confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2) with
      either a 30 degrees or wide-angle field-of-view. OCT3 imaging was performed in
      one of these patients. RESULTS: In the foveola, FAF and NIA were relatively
      normal. Parafoveal loss of retinal pigment epithelium (RPE) was indicated by
      absent FAF and NIA. An area of reduced FAF and NIA surrounded the parafoveal
      region of RPE loss. In the adjacent area, FAF was increased and increased NIA
      marked the peripheral border of increased FAF. Wide-field imaging revealed
      increased FAF in association with retinal vessels. Retinal thickness was markedly
      reduced in the OCT predominantly in the parafoveal region. Visual field loss and
      mfERG amplitude reduction corresponded to areas with increased or reduced FAF and
      NIA. CONCLUSION: Patterns of FAF and NIA indicate different stages of
      pathophysiologic processes involving lipofuscin and melanin in the RPE. Combined
      retinal imaging and functional testing provides further insights in the
      pathogenesis and development of retinal degenerative disease. An association of
      CQ retinopathy with retinal vessels architecture is hypothesized.

PMID- 18080822
TI  - The symptoms of autonomic dysfunction in HIV-positive Africans.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with
      autonomic neuropathy. The resultant autonomic dysfunction impairs quality of life
      and can have fatal consequences. Our aim was to clearly define the symptoms of
      autonomic dysfunction in African HIV-positive patients and determine whether
      these symptoms were related with (a) autonomic reflex responses (b) the degree of
      immunosupression. METHODS: Thirty-one HIV-positive treatment-naive African
      patients (mean CD4 cell count 269.5 +/- 253.4/mm3) and 12 healthy controls
      completed a detailed questionnaire (Autonomic System Profile, Mayo Clinic,
      Rochester, MN) relating to specific symptoms of autonomic dysfunction. After
      completion of the questionnaire, subjects underwent a standard battery of
      autonomic reflex tests. RESULTS: The autonomic symptom score was higher in the
      male HIV-positive patients (26.7 +/- 14.7 points) and female patients with CD4
      <200/mm3 (24.7 +/- 18.0) than sex-matched controls (male controls, 9.9 +/- 6.8, P
      < 0.05; female controls, 8.8 +/- 10.1; P < 0.05). Six patients had scores
      indicative of severe autonomic dysfunction (>43.8 points). The most common
      autonomic symptoms were: orthostatic intolerance, secretomotor and
      gastrointestinal dysfunction. There was no relationship between CD4 cell counts
      and autonomic symptom scores. The blood pressure response to sustained handgrip
      was blunted, but all other cardiovascular reflex tests were within the normal
      range or borderline. CONCLUSION: African HIV-positive patients report symptoms of
      autonomic dysfunction, despite normal or borderline autonomic reflex responses.

PMID- 18080823
TI  - Unusual presentation of infected vertebroplasty with delayed cement dislodgment
      in an immunocompromised patient: case report and review of literature.
AB  - Percutaneous vertebroplasty has been established as a safe and effective
      treatment for compression fractures of osteoporotic vertebrae. Complications of
      vertebroplasty, such as infection or anterior cement extrusion, are rare. Herein,
      we report an unusual presentation in an immunocompromised patient with an
      insidious infection of the disk. This infection resulted in dislodgment of the
      cement inferiorly and a compression fracture of the adjacent vertebra 6 months
      after vertebroplasty. We discuss the significance of this case and compare it
      with 7 others found in the literature.

PMID- 18080824
TI  - Intestinal bacterial overgrowth after Roux-en-Y gastric bypass.
AB  - The aim of the present study was to report the occurrence of serious
      subnutrition, associated to intestinal bacterial overgrowth, in two patients
      submitted to bariatric surgery. Two female patients (body mass index, 49 and 50
      kg/m(2), respectively) were submitted to Y-en-Roux gastric bypass. The first
      patient evolved a 52% loss of body weight within 21 months after surgery; the
      other, a 34% loss of initial body weight within 15 months after surgery, results
      corresponding, respectively, to 62 and 45 kg weight losses. However, both
      patients reported asthenia, hair fallout, and edema, and one also reported
      diarrhea, but none was feverish. Their respective albuminemias were of 24 and 23
      g/l. A respiratory hydrogen test suggested bacterial hyperproliferation. Thirty
      days after ciprofloxacin and tetracyclin treatments, they showed improved albumin
      levels and nutritional states, both confirmed by results of hydrogen breath
      tests. Bacterial overgrowth is an important complication that can compromise
      clinical evolution of patients submitted to intestinal surgery like gastroplasty
      with Y-Roux anastomosis. In cases of clinical suspicion or a confirmed diagnosis,
      adequate antibiotics, sometimes requiring to be cyclically repeated, should be
      administered.

PMID- 18080825
TI  - Severe obesity and P-wave dispersion: the effect of surgically induced weight
      loss.
AB  - BACKGROUND: Recent data have shown that obesity is an important potential risk
      factor for atrial fibrillation (AF). The mechanism of development of AF in
      obesity patients is still unclear and may be related to atrial refractoriness
      heterogeneity. The aim of our study was to determine the influence of bariatric
      surgery with a consequent substantial weight loss on P-wave dispersion in
      morbidly obese population. METHODS: We enrolled in this study 40 severe obese
      patients, and 40 age-matched non-obese healthy subjects were also recruited as
      controls. All subjects underwent conventional 12-lead electrocardiography for the
      analysis of P-wave dispersion. All subjects underwent bariatric surgery and were
      resubmitted to electrocardiography, biochemical, and anthropometric examination
      within 12 months after intervention. RESULTS: Severe obese patients had greater
      values in P-wave duration and dispersion than the normal weight controls.
      Bariatric surgery reduced significantly P-wave dispersion. There was a
      significant correlation between decrease of atrial refractoriness heterogeneity
      and bariatric-surgery-induced weight loss. CONCLUSIONS: In severe obese patients,
      surgically induced weight loss reduction is associated with significant decreased
      in P-wave dispersion. The reduction of the atrial refractoriness heterogeneity
      may be of clinical significance by reducing the risk of atrial fibrillation in
      morbidly obese subjects.

PMID- 18080826
TI  - Routine preoperative ultrasonography and selective cholecystectomy in
      laparoscopic Roux-en-Y gastric bypass. Why not?
AB  - BACKGROUND: Preoperative evaluation and treatment of biliary lithiasis in morbid
      obese patients who are candidates to bariatric surgery raise a series of
      questions which to date has no clear consensus. The aim of this study was to
      evaluate the results of routine preoperative abdominal ultrasonography and
      selective cholecystectomy comparing patients who underwent laparoscopic Roux-en-Y
      gastric bypass (RYGBP) with and without simultaneous cholecystectomy. METHODS:
      The prospective database of all the patients who underwent laparoscopic RYGBP in
      our institution was reviewed. The demographic characteristics, comorbidities,
      operative time, hospital stay, and postoperative complications were analyzed.
      RESULTS: From August 2001 to December 2006, 1,311 patients underwent laparoscopic
      RYGBP, 137 (10.4%) of them were excluded due to previous cholecystectomy. In 128
      (10.9%) of the remaining 1,174 patients, a cholecystectomy associated to
      laparoscopic RYGBP was performed. The mean age was 38.5 +/- 10.1 years, and 106
      (82.8%) were women. The mean operative time in patients with and without
      simultaneous cholecystectomy was 129.8 +/- 45 and 108.5 +/- 43 min, respectively
      (p < 0.001). The hospital stay was 3.6 +/- 0.8 days in patients with simultaneous
      cholecystectomy and 4 +/- 3 days in patients without simultaneous cholecystectomy
      (p = 0.003). There were no deaths. Postoperative complications were observed in 9
      (7%) and 73 (6.9%) patients with and without simultaneous cholecystectomy
      respectively (p = NS). Postoperative complications were not related to the
      cholecystectomy. CONCLUSION: Cholecystectomy associated to laparoscopic RYGBP
      should be considered in all patients with preoperative ultrasound diagnosis of
      cholelithiasis.

PMID- 18080828
TI  - Multicomponental fluorimetric determination of aluminium, gallium and indium.
AB  - For the fast characteristics of mixtures of Aluminium, Gallium and Indium the
      fluorimetric evaluation in the form of complexes with 8-Hydroxyquinoline-5
      sulphonic acid is described at selected pH. The highly collinear correlated
      fluorescent spectra and their first derivation were evaluated under various
      experimental conditions with the Multiple Linear Regression (MLR), Partial Least
      Squares (PLS) methods and Kalman filtering. When comparing the results, the PLS
      gives the least relative prediction errors under optimal conditions, 5.6-15.9%
      for the concentration range of Al 0.025-0.2 microg cm(-3), Ga 0.1-0.8 microgcm(
      3) and In 0.1-0.8 microg cm(-3) in the mixture.

PMID- 18080827
TI  - A literature review describing the role of return-to-work coordinators in trial
      programs and interventions designed to prevent workplace disability.
AB  - OBJECTIVE: Return-to-work (RTW) coordination has been suggested as an effective
      strategy for preventing workplace disability, but the scope of these services is
      not well described. The objective of this study was to describe the activities of
      RTW coordinators in published trials to provide a basis for establishing
      necessary competencies. METHODS: A keyword search of MEDLINE and CINAHL databases
      was conducted to identify intervention studies with a RTW coordinator providing
      direct, on-site workplace liaison to reduce work absences associated with
      physical health ailments. This search yielded 2,383 titles that were inspected by
      two examiners. Using a stepwise process that allowed for assessment of inter
      observer agreement, 90 full articles were selected and reviewed, and 40 articles
      (22 studies) met criteria for inclusion. RESULTS: All but two studies (of
      traumatic brain injury) focused on musculoskeletal conditions or work injuries.
      Twenty-nine RTW coordinator activities were identified, but there was variation
      in the training background, workplace activities, and contextual setting of RTW
      coordinators. Based on reported RTW coordinator activities, six preliminary
      competency domains were identified: (1) ergonomic and workplace assessment; (2)
      clinical interviewing; (3) social problem solving; (4) workplace mediation; (5)
      knowledge of business and legal aspects; and (6) knowledge of medical conditions.
      DISCUSSION: Principal activities of RTW coordination involve workplace
      assessment, planning for transitional duty, and facilitating communication and
      agreement among stakeholders. Successful RTW coordination may depend more on
      competencies in ergonomic job accommodation, communication, and conflict
      resolution than on medical training.

PMID- 18080829
TI  - HIV-related discrimination reported by people living with HIV in London, UK.
AB  - The objective was to examine the extent to which people living with HIV in London
      reported being discriminated against because of their infection. In 2004-2005,
      people living with HIV attending NHS outpatient HIV clinics in north east London
      were asked: "Have you ever been treated unfairly or differently because of your
      HIV status-in other words discriminated against?". Of the 1,687 people who
      returned a questionnaire (73% response rate), data from 1,385 respondents were
      included in this analysis; 448 heterosexual women and 210 heterosexual men of
      black African origin, 727 gay/bisexual men (621 white, 106 ethnic minority).
      Overall, nearly one-third of respondents (29.9%, 414/1,385) said they had been
      discriminated against because of their HIV infection. Of those who reported
      experiencing HIV-related discrimination, almost a half (49.6%, 200/403) said this
      had involved a health care worker including their dentist (n = 102, 25.3%) or
      primary care physician (n = 70, 17.4%).

PMID- 18080830
TI  - Assessing HIV/AIDS stigma and discrimination in developing countries.
AB  - HIV/AIDS-related stigma and discrimination are barriers to HIV prevention
      effectiveness, voluntary counseling and testing uptake, and accessing care in
      many international settings. Most published stigma scales are not comprehensive
      and have been primarily tested in developed countries. We sought to draw on
      existing literature to develop a scale with strong psychometric properties that
      could easily be used in developing countries. From 82 compiled questions, we
      tested a 50-item scale which yielded 3 dimensions with 22 items in pilot testing
      in rural northern Thailand (n = 200) and urban and peri-urban Zimbabwe (n = 221).
      The three factors (shame, blame and social isolation; perceived discrimination;
      equity) had high internal consistency reliability and good divergent validity in
      both research settings. Systematic and significant differences in stigmatizing
      attitudes were found across countries, with few differences by age or sex noted
      within sites. This short, comprehensive and standardized measure can be easily
      incorporated into questionnaires in international research settings.

PMID- 18080831
TI  - Improving the effectiveness of mental health services.

PMID- 18080832
TI  - Involvement of proteolytic activation of protein kinase R in the apoptosis of
      PC12 pheochromocytoma cells.
AB  - Protein kinase R (PKR) is a serine/threonine-specific protein kinase implicated
      in the control of cell growth, differentiation, interferon-induced antiviral
      response, and induction of apoptosis. It is activated by various stress signals
      and growth factors. Activated PKR phosphorylates the alpha subunit of eukaryotic
      initiation factor 2 (eIF2alpha), thereby inhibiting the initiation of
      translation. PKR also mediates the activation of several transcription factors
      (STAT1, p53, and NFkappaB) regulating both pro- and antiapoptotic mechanisms. In
      the present work, we studied the signaling pathways leading to PKR activation and
      apoptosis in PC12 rat pheochromocytoma cells, a model system of neuronal
      differentiation and cell death. We found that administration of various apoptosis
      inducing agents and conditions (serum starvation, anisomycin, LY294002,
      etoposide, and cisplatin) led to the proteolytic cleavage of PKR in PC12 cells.
      This cleavage was in strong correlation with the time kinetics of DNA
      fragmentation and morphological alterations characteristic of apoptosis. PKR was
      activated by the proteolytic cleavage: increased phosphorylation of eIF2alpha was
      found to run parallel with PKR cleavage. The activation of caspase-3 and caspase
      9 was stimulated by all apoptosis inducing agents used in this study. The
      activation of caspase-3 preceded the cleavage of PKR after serum withdrawal,
      anisomycin and etoposide treatment, while coincided with it in cells treated with
      LY294002 or cisplatin. These observations suggest that early activation of
      caspase-3 is upstream of PKR proteolysis and that proteolytic activation of PKR
      may play a general role in the apoptosis of PC12 cells induced by various forms
      of cellular stress.

PMID- 18080833
TI  - Estimation using penalized quasilikelihood and quasi-pseudo-likelihood in Poisson
      mixed models.
AB  - We consider two estimation schemes based on penalized quasilikelihood and quasi
      pseudo-likelihood in Poisson mixed models. The asymptotic bias in regression
      coefficients and variance components estimated by penalized quasilikelihood (PQL)
      is studied for small values of the variance components. We show the PQL
      estimators of both regression coefficients and variance components in Poisson
      mixed models have a smaller order of bias compared to those for binomial data.
      Unbiased estimating equations based on quasi-pseudo-likelihood are proposed and
      are shown to yield consistent estimators under some regularity conditions. The
      finite sample performance of these two methods is compared through a simulation
      study.

PMID- 18080834
TI  - Staging of early colorectal cancers: magnifying colonoscopy versus endoscopic
      ultrasonography for estimation of depth of invasion.
AB  - BACKGROUND AND AIMS: Preoperative estimation of depth of invasion in early
      colorectal cancers (CRCs) is essential for patient management. This study was
      conducted to compare the diagnostic accuracies of magnifying colonoscopy and
      endoscopic ultrasonography (EUS) for estimating the depth of invasion of early
      CRCs. SUBJECTS AND METHODS: A total of 438 early CRCs were removed endoscopically
      or surgically from July 1993 through March 1999 at our hospital. Before removal,
      102 lesions were evaluated with both magnifying colonoscopy and EUS and were
      included in this analysis. The diagnostic accuracy of each method, referring to
      the histology of the resected specimens, was evaluated. RESULTS: The overall
      diagnostic accuracies were 87% (89/102) for magnifying colonoscopy and 75%
      (76/102) for EUS (P = 0.0985). Subgroup analysis was also done for polypoid and
      non-polypoid lesions. For polypoid lesions, the overall diagnostic accuracies of
      magnifying colonoscopy and EUS were 88% (60/68) and 72% (49/68), (P = 0.0785),
      and for non-polypoid lesions, they were 85% (29/34) and 79% (27/34), (P =
      0.7169). CONCLUSION: Although, there is a substantial difference in the overall
      diagnostic accuracies, it is not statistically significant. Therefore, we
      conclude that magnifying colonoscopy is at least as accurate as EUS for
      preoperative staging of early CRCs.

PMID- 18080835
TI  - Regulatory effects of mechanical strain on the chondrogenic differentiation of
      MSCs in a collagen-GAG scaffold: experimental and computational analysis.
AB  - The effective treatment of cartilage defects by tissue engineering requires an
      improved understanding of the effect of mechanical forces on cell differentiation
      within three-dimensional (3D) matrices. The objective of this study was to
      investigate the effects of mechanical constraint and cyclic tensile strain on the
      chondrogenic differentiation of mesenchymal stem cells (MSCs) in a 3D collagen
      type I-glycosaminoglycan (GAG) scaffold. A multi-station uniaxial stretching
      bioreactor was fabricated to facilitate application of cyclic strain to the
      constructs cultured in a chondrogenic medium. Mechanical constraint, created by
      uniaxial clamping, prevented the cell-mediated contraction of the scaffolds and
      resulted in a reduction in the rate of GAG synthesis as measured by [35S] sulfate
      incorporation relative to unconstrained controls. However, the rate of GAG
      synthesis was increased following application of continuous 10% cyclic tensile
      loading at 1 Hz for 7 days. A poroelastic finite element analysis of the 3D
      scaffold computed a maximum fluid flow of 19 microm/s and maximum principal
      strains of 8% under 10% stretch suggesting these magnitudes were sufficient to
      mechano-regulate the chondrogenic differentiation process.

PMID- 18080836
TI  - 'Encounters with experience': empirical bioethics and the future.

PMID- 18080838
TI  - Evaluation of relationship between meteorological parameters and air pollutant
      concentrations during winter season in Elazig, Turkey.
AB  - In recent years, due to the rapid increase in population density, building
      density and energy consumption, the outdoor air quality has deteriorated in the
      crowded urban areas of Turkey. Elazig city, which is located in the east Anatolia
      region of Turkey, is also influenced by air pollutants. In the present study,
      relationship between monitored air pollutant concentrations such as SO2 and the
      total suspended particles (TSP) data and meteorological factors such as wind
      speed, temperature, relative humidity, solar radiation and atmospheric pressure
      was investigated in months of October, November, December, January, February, and
      March during the period of 3 years (2003, 2004 and 2005) for Elazig city.
      According to the results of linear and non-linear regression analysis, it was
      found that there is a moderate and weak level of relation between the air
      pollutant concentrations and the meteorological factors in Elazig city. The
      correlation between the previous day's SO2, TSP concentrations and actual
      concentrations of these pollutants on that day was investigated and the
      coefficient of determination R2 was found to be 0.64 and 0.54, respectively. The
      statistical models of SO2 and TSP including all of meteorological parameters gave
      R2 of 0.20 and 0.12, respectively. Further, in order to develop this model,
      previous day's SO2 and TSP concentrations were added to the equations. The new
      model for SO2 and TSP was improved considerably with R2 = 0.74 and 0.61,
      respectively.

PMID- 18080837
TI  - Radiation therapy in acromegaly.
AB  - Radiation therapy is generally not a primary treatment modality for growth
      hormone-secreting pituitary adenomas. However, in patients with acromegaly
      refractory to medical and/or surgical interventions, radiation can offer durable
      tumor control and often biochemical remission. Technique of radiation therapy
      delivery and dose vary by adenoma size and extrasellar extension. Radiation can
      be delivered in a single sitting by stereotactic radiosurgery or in fractionated
      form of smaller doses delivered over typically 5-6 weeks in 25-30 treatments. A
      brief overview of forms of radiation modalities is reviewed followed by
      discussion of the role for radiation therapy, rationale of delivery method, and
      potential adverse effects.

PMID- 18080839
TI  - Comparing the therapeutic outcome of different alpha-blocker treatments for BPH
      in the same individuals.
AB  - OBJECTIVE: Alpha-blockers are the most widely used agents to treat lower urinary
      tract symptoms in males, and switching between alpha-blockers is a frequent
      management option when the desired effect could not be obtained. There is no data
      in the literature that reveal the outcome of treatments with different alpha
      blockers within the same patient. We sought the answer to this question in a
      setting where the same individuals were treated with two different agents during
      different time frames. MATERIALS AND METHODS: Forty males with benign prostatic
      hyperplasia (BPH) applying to the Department of Urology with lower urinary tract
      symptoms (LUTS) were enrolled in the study consecutively. Patients were evaluated
      with detailed medical history, IPSS forms, digital rectal examination (DRE),
      urinary ultrasound, PSA, and uroflowmetry. The subjects received terazosin 5 mg
      daily for 3 months, and controlled release form of alfuzosin 10 mg daily for
      another 3 months, leaving a 1-month clearance period in between. The above
      mentioned detailed evaluations were carried out before and after each alpha
      blocker regimen. RESULTS: Mean age and PSA level was 63.3+/-1.6 years (45-80),
      and 2.1+/-0.4 ng/ml (0.16-6.3 ng/ml). IPSS and Qmax values before treatment with
      terazosin and alfuzosin were similar. Improvements in IPSS and Qmax values after
      treatments with both terazosin and alfuzosin were significant. There was no
      statistically significant difference between the drugs in terms of percent
      improvements in IPSS and Qmax with alpha-blocker treatment. No untoward effect
      except for transient dizziness in one case with terazosin treatment was
      encountered. CONCLUSION: Different alpha-blockers, which are used during
      different time frames in the same individuals, provide similar efficiency
      outcome. When the desired effect in the treatment for BPH could not be obtained
      with one alpha-blocker, there may not be any benefit in switching to another one.

PMID- 18080840
TI  - Identification of the tree shrew ATP-binding cassette transporter A1 (ABCA1) and
      its expression in tissues : cDNA sequence and expression of tree shrew ABCA1.
AB  - ATP-binding cassette transporter A1 (ABCA1) modulates plasma levels of high
      density lipoprotein (HDL), a cardiovascular protecting factor. Tree shrew was
      considered to be an animal protected from atherosclerosis characterized by high
      proportion of HDL in plasma. The cDNA clones and expression of tree shrew ABCA1
      was identified using SMART-RACE and Real-Time PCR techniques respectively. The
      nucleotide sequence of tree shrew ABCA1 covered 7,762 bp, including a 6,786 bp
      coding region which encoded a 2,261 amino acids protein with the high identity to
      human ABCA1 (95%). Tree shrew ABCA1 was expressed in various tissues, the highest
      in lung, followed by liver, kidney, spleen and cardiac muscle in turn from high
      to medium expression levels. This pattern was partially different from that of
      human ABCA1 which was low in kidney and cardiac muscle. This work could shed new
      light on its role of ABCA1 in the distinctive HDL metabolism in tree shrew.

PMID- 18080841
TI  - Expression and purification of Zantedeschia aethiopica agglutinin in Escherichia
      coli.
AB  - Recombinant Zantedeschia aethiopica agglutinin (ZAA) was expressed in Escherichia
      coli as N-terminal His-tagged fusion. After induction with isopropylthio-beta-D
      galactoside (IPTG), the recombinant ZAA was purified by metal-affinity
      chromatography. The purified ZAA protein was applied in anti-fungal assay and the
      result showed that recombinant ZAA had anti-fungal activity towards leaf mold
      (Fulvia fulva), one of the most serious phytopathogenic fungi causing significant
      yield loss of crops. This study suggests that ZAA could be an effective candidate
      in genetic engineering of plants for the control of leaf mold.

PMID- 18080842
TI  - Molecular cloning and preliminary analysis of the human alpha-methylacyl-CoA
      racemase promoter.
AB  - Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in beta-oxidation of
      branched-chain fatty acids and bile acid intermediates. Recent works have
      revealed that AMACR is overexpressed in prostate cancer and functionally
      important for the growth of prostate cancer cells. Despite the recent interest in
      AMACR as a diagnostic marker for prostate cancer, little is known about the
      transcriptional regulation of AMACR in prostate cancer. To elucidate the
      regulation of the AMACR gene, a 2.3-kb fragment of its 5' flanking region was
      cloned into pGL3-Basic, then using tansfection and Dual-luciferase reporter
      assay, a preliminary analysis on promoter activity and function of this 2.3-kb
      sequence was carried out. This 2.3-kb fragment represented promoter activity that
      consistent with the expression level in LNCaP and PC-3 cells respectively.
      Transfection experiments of 5'-deletion mutants into LNCaP cells revealed a
      positive-regulatory region located between nucleotides -423 and -93 that may be
      responsible for AMACR transactivation in LNCaP cells. Cotransfection experiments
      revealed that promoter activity of this 2.3-kb sequence was down-regulated by
      C/EBPalpha, p53, NF-kappaB p50. And data from luciferase-based reporter assays
      suggest that the promoter function of AMACR is independent of androgen receptor
      mediated signaling.

PMID- 18080843
TI  - Association of the mutation for the human carboxypeptidase E gene exon 4 with the
      severity of coronary artery atherosclerosis.
AB  - OBJECTIVE: To test the hypothesis that the identification of mutation in the
      carboxypeptidase E (CPE) gene which leads to marked hyperproinsulinaemia is
      consistent with a possible role for mutations in CPE in the development of
      coronary atherosclerosis. METHODS: The study subjects consisted of 1084
      consecutive patients (812 males and 272 females) who will undergo coronary
      angiography. The severity of coronary atherosclerosis was defined by the
      Gensini's score system. The proinsulin level was measured using highly sensitive
      two-site sandwich ELISA methods. Screening for mutations of the 4th exon and exon
      intron junctional region of the CPE gene was performed by polymerase chain
      reaction followed by bidirectional sequencing. RESULTS: Sequencing of the CPE
      gene exon 4 in 1084 consecutive patients revealed 2 genetic variants, the G-to-A
      substitution at nucleotide 2855 in exon 4 (synonymous mutation) and A-to-G
      substitution at nucleotide 2925 in intron 4. Although the proinsulin level was
      not influenced by the presence of the two point mutation, the Gensini score was
      significantly influenced by the presence of the A2925G mutant (P = 0.023).
      Furthermore, we found a higher prevalence of subjects with the A2925G
      heterozygous mutant among higher Gensini score subjects than it among lower
      Gensini score subjects, and this difference reached statistical significance (P =
      0.006, OR 1.465, 95%CI 1.116-1.924). In addition, the frequency distribution of
      the G2855A mutant was differed in the higher Gensini score subjects than it in
      the lower Gensini score subjects belonging to high-risk category as smokers, and
      the statistical significance was reached (P = 0.043, OR 2.075, 95%CI 1.024
      4.207). CONCLUSIONS: In the present study, the severity of the coronary
      atherosclerosis estimated by Gensini score was significantly influenced by the
      presence of the A2925G mutant and G2855A mutant of the CPE gene, and the exactly
      mechanism underlying the association needs further study.

PMID- 18080844
TI  - Clinical significance of tumor location in remnant gastric cancers developed
      after partial gastrectomy for primary gastric cancer.
AB  - We sought to elucidate the clinical value of tumor location of the remnant
      gastric cancer developed after partial gastrectomy for gastric cancer to
      determine the disease characteristics and surgical outcome. Fifty-two patients
      underwent a second operation with a curative intent because of remnant gastric
      cancer after undergoing partial gastrectomy for gastric cancer between 1995 and
      2005. The clinicopathological features of their primary and recurrent diseases,
      surgical results, and survivals according to tumor sites within the remnant
      stomach were examined. Tumors that developed at the anastomotic site (n = 27) in
      remnant stomach favored a female gender, younger age, and unfavorable
      histological characteristics of primary and recurrent diseases and were also
      associated with lower tumor resectability than those that developed in the non
      anastomotic site (n = 25). The overall 5-year survival rates of patients that
      experienced an anastomotic recurrence and non-anastomotic recurrence were 36.9
      and 95.8% (p = 0.001), respectively, and the overall 5-year survival rates of
      patients with stage I primary gastric cancer were 83.3 and 100% (p = 0.018) for
      anastomotic and non-anastomotic recurrence. Tumor location of remnant gastric
      cancer is an important factor for predicting surgical outcome, but it also
      reflects the characteristics of primary and recurrent diseases. It is hoped that
      these results will assist surgeons establishing the treatment plan for remnant
      gastric cancer.

PMID- 18080845
TI  - Central expressions of ghrelin and cholecystokinin in rats with gastric
      electrical stimulation.
AB  - BACKGROUND: Gastric electrical stimulation (GES) has recently been proposed for
      the treatment of obesity. The aim of this study was to explore the possible
      central mechanisms involved in GES by investigating the expression of orexigenic
      and anorexigenic peptides in the rodent hypothalamus and hippocampus. METHODS:
      The experiment was designed in two parts: an acute experiment with 2 h GES and a
      chronic experiment with 14-day continuous GES. After stimulation, the expressions
      of an orexigenic hormone, ghrelin, in the hypothalamus and an anorexigenic
      hormone, cholecystokinin (CCK), in the hippocampus were detected by the
      immunohistochemical method. GES was performed using parameters similar to those
      used in clinical studies for treating obesity. RESULTS: Compared with the control
      group, 2 h GES resulted in a decrease in the number of ghrelin-immunoreactive
      (ghrelin-IR) neurons in the hypothalamic paraventricular nucleus (PVN, 34.8 +/-
      1.86 vs 57.2 +/- 2.95, P = 0.02) and the supraoptic nucleus (SON, 51.2 +/- 3.21
      vs 82.8 +/- 3.08, P = 0.01); the CCK-immunoreactive (CCK-IR) neurons in the
      hippocampus were of no changes (7.4 +/- 0.87 vs 6.2 +/- 0.58, P = 0.29). After
      the 14-day GES, the number of CCK-IR neurons in the hippocampus was increased
      compared with that of the control group (4.0 +/- 0.32 vs 2.4 +/- 0.51, P = 0.03).
      However, there were no changes in the number of ghrelin-IR neurons either in the
      PVN or in the SON. CONCLUSIONS: These results indicate that the expression of
      ghrelin and CCK can be altered by GES. GES may be able to alter energy
      homeostasis by modulating the expressions of food intake-related hormones in the
      central nervous system: reducing the level of orexigenic ghrelin acutely and
      increasing the level of anorexigenic CCK chronically.

PMID- 18080847
TI  - Spinocerebellar ataxia type 7 presenting as Stargardt's disease.

PMID- 18080846
TI  - Comparison of weight loss and morbidity after gastric bypass and gastric banding.
      A single center European experience.
AB  - BACKGROUND: Gastric bypass and gastric banding are widely used to treat morbid
      obesity and both procedures offer certain advantages. The indication for these
      two treatment options continue to be subject to debate. METHODS: A single-center
      case-controlled matched-pair cohort study was performed. Fifty-three primary
      gastric bypass patients (GB) operated between January 2002 and May 2005 were
      matched by gender, age, race, and initial bodyweight to 53 patients who underwent
      laparoscopic adjustable gastric banding (LAGB) in the same time period. RESULTS:
      Both groups were comparable regarding age, race, gender, preoperative body mass
      index, and excessive weight. Severe early complications occurred in six patients
      (11.3%) in the GB group and were not seen in the LAGB group. Severe late
      complications occurred in three patients (5.7%) in the GB group and one patient
      (1.9%) in the LAGB group. No mortality occurred in either group. Weight loss was
      significantly lower in the LAGB group than in the GB group at all time points
      during the follow-up. Significantly more patients were treated successfully
      (excess weight loss >50%) in the GB group than in the LAGB group. After 2 years,
      76% of the patients in the GB group were treated successfully versus 40% of the
      patients in the LAGB group (P = 0.03). CONCLUSION: Gastric bypass and gastric
      banding are safe and without mortality. Gastric bypass is more effective in terms
      of weight loss and the number of successfully treated patients. Gastric banding
      is a procedure with less severe complications.

PMID- 18080848
TI  - Screening for POLG1 mutations in a Southern Italian ataxia population.

PMID- 18080849
TI  - MRI and SPECT of midbrain and striatal degeneration in fragile X-associated
      tremor/ataxia syndrome.

PMID- 18080850
TI  - Plasma levels of nitric oxide and stroke outcome.
AB  - Production of reactive oxygen species after cerebral blood flow disruption may
      enhance tissue damage through multiple molecular pathways. Changes in nitric
      oxide (NO) metabolism and oxidative stress status were investigated in 47
      patients with ischemic stroke by measuring plasma nitric oxide (NO) and
      peroxynitrite (ONOO(-)) levels.A correlation was sought between these two
      parameters and i) baseline stroke severity based on the National Institute of
      Health stroke scale (NIHSS) and ii) neurological outcome in terms of NIHSS
      changes from entry (T(0)) to 30 days after symptom onset (T(1)). The control
      group consisted of 30 age- and sex-matched healthy subjects. Mean plasma levels
      of ONOO(-) (arbitrary fluorescence number +/- SD) were significantly higher in
      patients (7.70 +/- 1.71 vs 5.35 +/- 0.69, p < 0.001), whereas mean NO levels
      (nmol/mg protein) were significantly higher in controls (115.40 +/- 12.40 vs.
      51.10 +/- 12.50, p < 0.001). Plasma ONOO(-) was significantly higher among
      patients with non-lacunar stroke (8.48 +/- 1.50 vs. 6.95 +/- 1.58 in those with
      lacunar stroke; p = 0.001), whereas NO levels were significantly higher among
      lacunar stroke patients (60.00 +/- 7.86, vs. 41.77 +/- 9.29 in patients with
      nonlacunar stroke; p < 0.001). Nitric oxide plasma levels were also associated
      with an unfavorable evolution in non-lacunar stroke, since a 10 unit increase in
      NO predicted a 1 point reduction in the NIHSS score at T1. Findings show that
      changes in NO metabolism may be considered as markers of brain injury in patients
      with ischemic stroke. Further work is needed to establish whether the amount of
      biochemical changes related to oxidative stress may influence outcome in these
      patients.

PMID- 18080852
TI  - Acute transverse myelitis with normal brain MRI : long-term risk of MS.
AB  - OBJECTIVE: To investigate the long-term risk of developing MS in patients
      presenting with acute transverse myelitis (ATM) and normal brain MRI scans at
      onset. METHODS: We studied 58 ATM patients with normal brain MRI at presentation
      for up to 5 years with serial neurologic and imaging studies. All patients
      underwent CSF analysis at onset which was defined positive if two or more IgG
      oligoclonal bands and/or elevated IgG index were present. Brain and spinal cord
      MRI scans were obtained every 6 months for the first 2 years, and annually
      thereafter unless the patient experienced a second neurologic attack different
      from the initial episode to confirm CDMS or there was demonstration of MRI
      lesions confirming dissemination in time and space to fulfill McDonald imaging
      criteria to diagnose MS. RESULTS: Seventeen of 58 (29%) patients developed MS of
      which 7 (41%) patients developed CDMS and 10 (59%) developed MS using McDonald
      Imaging Criteria. Mean time to CDMS by a second clinical attack was 11. 1 months
      compared to 19. 2 months by MRI lesions (P = 0. 03). None of the patients
      developed MS after 24 months of onset. All 17 patients who developed MS had
      positive CSF although 15 patients who had positive CSF did not develop MS during
      the 5 years of follow-up. CONCLUSIONS: The majority of patients with ATM and
      normal brain MRI do not develop MS after 5 years of follow-up confirming the
      relatively low risk compared to patients with abnormal brain MRI scans. CSF is
      helpful in distinguishing patients more likely to develop MS. Compared to
      clinical attacks, serial imaging may not lead to an earlier diagnosis in ATM
      patients with normal brain MRI.

PMID- 18080853
TI  - Hyperhomocysteinemia is associated with cognitive impairment in multiple
      sclerosis.
AB  - Hyperhomocysteinemia (HHcy) has been associated with cognitive impairment in
      various neurological diseases. Cognitive impairment occurs early in multiple
      sclerosis (MS). Conflicting data have been reported regarding plasma total
      homocysteine (tHcy) levels in MS patients, and the impact of HHcy on cognitive
      impairment in MS is not known. This study investigated whether plasma total
      homocysteine levels are increased in MS and if HHcy is associated with cognitive
      impairment in MS. We compared tHcy levels in 94 patients with MS and 53 healthy
      age-matched controls. We used a neuropsychological test battery that included the
      Raven's Coloured Progressive Matrices, the Visual Search Test, the Trail Making
      Test A and B, the Immediate and Delayed Recall of a Short Story, the 30 Paired
      Word Associates, the Rey-Osterrieth Complex Figure Test, and the Semantic and
      Verbal Fluency Tests. Clinical (sex, age, type of MS, relapse, disease duration,
      coexisting disease, smoking habit, and physical disability) and laboratory
      variables (HHcy, low serum levels of folate and vit.B12, MTHFR genotype) were
      evaluated for their ability to predict cognitive impairment. The mean tHcy was
      higher in patients (13.19 micromol/L, SD5.58) than in controls (9.81 micromol/L,
      SD2.53; p < 0.001). Univariate analysis determined the following factors to be
      associated with cognitive impairment: higher age at observation, chronic
      progressive course of disease, longer disease duration,moderate or severe
      physical disability, and frequency of HHcy. With multivariate regression
      analysis, there remained a significant association only between frequency of HHcy
      and cognitive impairment (beta 0.262, p = 0.01). We conclude that tHcy levels are
      increased in MS and that HHcy is associated with cognitive impairment in this
      disease.

PMID- 18080855
TI  - Marked differences in prevalence of multiple sclerosis between ethnic groups in
      Oslo, Norway.
AB  - OBJECTIVES: Oslo, the capital of Norway, has a high prevalence of multiple
      sclerosis (MS). In recent decades there has been substantial immigration to Oslo
      from Asia, the Middle East and Africa. The aim of the study was to estimate the
      prevalence of MS among non-Western immigrants living in Oslo, adjusted for
      duration of residence. METHODS: Data were obtained from the MS registry at
      Ulleval University Hospital. The prevalence of MS was adjusted for ethnicity, age
      and duration of residence in Norway. RESULTS: A total of 786 definite MS patients
      were alive and resident in Oslo on 31 December 2005, yielding a crude prevalence
      of 148/10(5). Twenty-seven patients were of non-Western origin: Middle East 14,
      Asia 9, Africa 4. The non-Western patients' mean age at migration was 20. The
      crude prevalence (95 % CI) of MS patients was 170/10(5) (159-182) for the
      Norwegian/Western, 85/10(5) (50-143) for the Middle East, 21/10(5) (11-41) for
      the Asian, and 20/10(5) (7-53) for the African cohorts. The high MS prevalence in
      the Middle East cohort and the low prevalence among Asian/African immigrants were
      also pronounced after adjustment for age and duration of residence. CONCLUSIONS:
      The Middle East immigrants had a markedly higher prevalence of MS despite a
      shorter duration of residence than other non-Western patients. These findings
      suggest that people from the Middle East have a greater genetic disposition for
      MS. Furthermore, the high age at migration among the non-Western immigrants
      indicates that possible environmental factors affecting MS risk may also act on
      adults.

PMID- 18080856
TI  - MR imaging of brainstem atrophy in progressive supranuclear palsy.
AB  - BACKGROUND: To enhance the sensitivity and specificity of the clinical diagnosis
      of progressive supranuclear palsy (PSP), neuroradiological parameters established
      in pathologically proven cases are needed. METHODS: We examined brainstem atrophy
      in five pathologically confirmed PSP patients (three men, mean age at death 77
      years, range 64-84 years). Time interval between symptom onset and MRI ranged
      from 1 to 5 years, and between MRI and death from 33 to 52 months. Only one
      patient had clinical diagnosis of PSP at the time of MRI. Control group consisted
      of 19 age- and gender-matched healthy subjects. Seventeen morphometric parameters
      of the midbrain and pons were measured on T1-weighted midsagittal and T2-weighted
      axial MRI scans with Image Analyzer. Measurements of superior cerebellar peduncle
      (SCP) width were performed on PSP autopsy specimens. RESULTS: Mean SCP width on
      MRI in PSP (2.7 +/- 0.8 mm, 95%CI: 2.1-3.3) was smaller than in controls (3.7 +/-
      0.5 mm, 95%CI: 3.5-3.9). Mean SCP width at autopsy was 8% smaller than mean SCP
      width on MRI. Midsagittal midbrain area in PSP (99.1 +/- 6.9 mm(2), 95%CI: 90.5
      107.6) was smaller than in controls (141.0 +/- 18.1 mm(2), 95%CI: 132.2-149.7).
      Midbrain/pons area ratio in PSP was 1:5 and in controls was 1:4 (p < 0.01).
      Repeat MRI 17 months later in one PSP case revealed 30% decrease of SCP width.
      CONCLUSIONS: MR imaging with quantitative analysis may be useful in the diagnosis
      of early PSP and in monitoring disease course.

PMID- 18080854
TI  - High field MR imaging and 1H-MR spectroscopy in clinically isolated syndromes
      suggestive of multiple sclerosis: correlation between metabolic alterations and
      diagnostic MR imaging criteria.
AB  - PURPOSE: To prospectively investigate metabolic changes in the normal-appearing
      white matter (NAWM) of patients presenting with clinically isolated syndromes
      (CIS) suggestive of multiple sclerosis (MS) and to correlate these changes to
      conventional MR imaging findings in terms of MR imaging criteria. MATERIALS AND
      METHODS: Multisequence MR imaging of the brain and (1)H-MR spectroscopy of the
      parietal NAWM were performed in 31 patients presenting with CIS and in 20
      controls using a 3. 0 T MR system. MR imaging criteria and International Panel
      criteria were assessed based on imaging, clinical and paraclinical results.
      Metabolite ratios and absolute concentrations of N-acetyl-aspartate (tNAA),
      myoinositol (Ins), choline (Cho), and total creatine (tCr) were determined. The
      metabolite concentrations were correlated with the fulfilled MR imaging criteria.
      RESULTS: In comparison to the control group, the CIS group showed significantly
      decreased mean tNAA concentrations (-8. 1%, p = 0. 012). Significant changes
      could not be detected regarding Ins, tCr and Cho. No significant correlations
      between absolute metabolite concentrations and MR imaging criteria were observed.
      Patients with and without a lesion dissemination in space showed no significant
      differences of their metabolite concentrations. CONCLUSION: As assessed by (1)H
      MRS a significant axonal damage already occurs during the first demyelinating
      episode in patients with CIS. Conventional MR imaging in terms of diagnostic
      imaging criteria does not significantly reflect NAWM disease activity in terms of
      metabolic alterations detected by (1)H-MR spectroscopy.

PMID- 18080857
TI  - Impact of psychiatric disorders on Parkinson's disease : a nationwide follow-up
      study from Sweden.
AB  - OBJECTIVES: To analyze whether hospitalization for a psychiatric disorder
      predicts Parkinson's disease (PD) in men and women in different age groups after
      accounting for socioeconomic status and geographical region. METHODS: Data from
      the MigMed database were used to identify all people in Sweden hospitalized for
      psychiatric disorder and PD during the study period (1987 to 2001). Standardized
      incidence ratios (SIRs) with 95% confidence intervals (CI) for PD were calculated
      among those with and without hospitalization for psychiatric disorder. RESULTS:
      There were 1876 cases of PD among those with psychiatric disorder during the
      study period. The risk of developing PD was strongest among those under age 50;
      the SIR was 11.56 (95% CI 9.15-14.41). The risk was attenuated with increasing
      age in both men and women. There were similar risk patterns in all subtypes of
      psychiatric disorders in PD patients. The overall risk of PD among people with
      psychiatric disorders was higher for women than men. CONCLUSIONS: A psychiatric
      disorder is an appreciable risk factor for the development of PD, particularly in
      people under age 50. The association between PD and psychiatric disorders should
      be taken into account by clinicians and health care providers.

PMID- 18080858
TI  - Viral outcome of simian-human immunodeficiency virus SHIV-89.6P adapted to
      cynomolgus monkeys.
AB  - Simian-human immunodeficiency virus (SHIV) 89.6P is considered to be one of the
      most pathogenic chimeric viruses in rhesus macaques. However, when crossing from
      one to another species of monkeys the pathogenicity of this virus may be
      affected. By using SHIV-89.6P(cy243), a virus obtained by passaging SHIV-89.6P in
      cynomolgus macaques, we investigated the dynamics of viral replication and the
      impact of the inoculum size (from 10 up to 50 monkey infectious dose) on the
      progression of the infection in 22 cynomolgus macaques. SHIV-89.6P(cy243 )caused
      massive depletion of CD4+ T-cells within 4 weeks of the inoculum, followed by an
      irreversible immune deficiency in a high proportion of the infected monkeys. This
      study demonstrates that SHIV-89.6P(cy243) is pathogenic in cynomolgus macaques
      and that the dynamics of the viral replication and the rate of clinical
      progression depend on the size of the inoculum. Our findings provide unique and
      relevant data, particularly with regard to the value of the in vivo titration
      used to select the most appropriate infectious dose to study the "virus-host"
      interplay.

PMID- 18080859
TI  - Ambient air monitoring of Beijing MSW logistics facilities in 2006.
AB  - In China, "green" integrated waste management methods are being implemented in
      response to environmental concerns. We measured the air quality at several
      municipal solid waste (MSW) sites to provide information for the incorporation of
      logistics facilities within the current integrated waste management system. We
      monitored ambient air quality at eight MSW collecting stations, five transfer
      stations, one composting plant, and five disposal sites in Beijing during April
      2006. Composite air samples were collected and analyzed for levels of odor,
      ammonia (NH3), hydrogen sulfide (H2S), total suspended particles (TSPs), carbon
      monoxide (CO), sulfur dioxide (SO2), and nitrogen dioxide (NO2). The results of
      our atmospheric monitoring demonstrated that although CO and SO2 were within
      acceptable emission levels according to ambient standards, levels of H2S, TSP,
      and NO2 in the ambient air at most MSW logistics facilities far exceeded ambient
      limits established for China. The primary pollutants in the ambient air at
      Beijing MSW logistics facilities were H2S, TSPs, NO2, and odor. To improve
      current environmental conditions at MSW logistics facilities, the Chinese
      government encourages the separation of biogenic waste from MSW at the source.

PMID- 18080860
TI  - The ecological impact of four IGR insecticides in adults of Hyposoter didymator
      (Hym., Ichneumonidae): pharmacokinetics approach.
AB  - Adults of the parasitoid Hyposoter didymator were topically treated with four
      insect growth regulator (IGR) insecticides at different doses, including their
      respective maximum field recommended concentrations (MFRCs) [registered in Spain
      or recommended by manufacturers]. Methoxyfenozide and tebufenozide (100, 500 and
      1,000 mg/l) did not affect any life parameter or the first parasitoid's
      offspring. In contrast, diflubenzuron (100, 500 and 1,000 mg/l) and pyriproxyfen
      (75, 500 and 1,000 mg/l) caused sublethal effects, decreasing the offspring
      emergence as a result of the parasitoid mortality during its immature stages
      inside the host and the life span of female offspring. In a second part,
      pharmacokinetic studies using a (14)C isotope of each IGR showed similar patterns
      of penetration through the cuticle, but different absorption and distribution
      rates inside the insect body. Cuticular penetration of pyriproxyfen reached about
      99% in 3 days and those of diflubenzuron, methoxyfenozide and tebufenozide ranged
      from 82% to 86%. All insecticides were recovered from the reproductive system of
      insects and eggs. For pyriproxyfen and diflubenzuron absorption in the adult body
      tissues reach >65%, whereas this was only 40% for tebufenozide and
      methoxyfenozide. No statistical differences were found between sexes. The current
      data reflect that several mechanisms are likely to be involved in the selectivity
      of these products towards this parasitoid.

PMID- 18080861
TI  - Hypothesis: human serum-borne albumin bound lipids promote cellular survival
      after apoptosis induction by a variety of stimuli.
AB  - A tight control of proliferation and cell death is required to maintain
      homeostasis in multicellular organisms. Several specific pro- and anti-apoptotic
      regulators and pathways have been deciphered being responsible for these complex
      tasks. Here we describe a human serum-borne activity promoting cellular fitness
      and inhibiting apoptosis after a plethora of different cell death stimuli. The
      factor(s) do not inhibit a specific death pathway, instead it/they can be
      considered as general pro-survival factor(s) for cultured cells. The activity is
      heat stable (30 min, 96 degrees C), co-migrates with albumin in size exclusion
      chromatography, and is sensitive to chemical delipidation. A similar activity is
      observed in native, non-delipidated preparations of human albumin, while
      delipidated albumin is not effective. These properties point to heat stable
      factors that exert anti-apoptotic activities, most likely albumin bound bioactive
      lipids. The activity prevented Akt dephosphorylation and degradation, after
      apoptosis induction by staurosporine and the production of reactive oxygen
      species after UV-B irradiation. In conclusion human serum-enriched bioactive
      lipids promote survival of cultured cells overriding the pro-apoptotic effects of
      a variety of apoptosis inducing agents.

PMID- 18080862
TI  - Polyketide analysis using mass spectrometry, evaporative light scattering, and
      charged aerosol detector systems.
AB  - In this study, a mass spectrometer (MS), an evaporative light scattering detector
      (ELSD), and a charged aerosol detector (CAD) were used to analyze an erythromycin
      precursor (termed 6-deoxyerythronolide B). The work highlights the capabilities
      of each detector to analyze a representative polyketide compound that does not
      possess a natural chromophore, and presents the first comparison to include a
      charged aerosol system. Each detector was evaluated based upon limit of detection
      (LOD), dynamic range, and precision in the context of polyketide analysis. Due to
      its low LOD, wide dynamic range, and ability to provide molecular weight
      information, the MS was deemed the best detection option for the analysis of low
      concentration, poorly identified polyketide compounds. Alternatively, both the
      CAD and ELSD systems studied showed better precision and accuracy. The ELSD
      demonstrated the best precision at 3%, but its LOD was limited to concentrations
      primarily greater than or equal to 1 mg/L. The Corona CAD demonstrated a LOD
      (0.012 mg/L) and dynamic range comparable to mass spectroscopy and therefore
      serves as a more cost-efficient alternative for polyketide production schemes
      with low titers.

PMID- 18080863
TI  - The importance of electron microscopy in the study of capillary endothelial
      cells: an historical review.
AB  - The second half of the 20th century has witnessed the birth and growth of
      biological ultrastructural research in which electron microscopy plays a crucial
      role. The electron microscope has contributed greatly to biology and medicine, as
      is clearly indicated by the large number of publications devoted to reporting
      observations on the fine structure of biological specimens. Ultrastructural
      studies, initially concerned with macromolecular complexes, had by the mid-1950s
      revealed a previous unimaginable complexity in the organization of the eukaryotic
      cell. This review article summarizes the literature data concerning the important
      role played by the electron microscope in the study and characterization of
      capillary endothelial cells.

PMID- 18080864
TI  - Low shear stress-induced interleukin-8 mRNA expression in endothelial cells is
      mechanotransduced by integrins and the cytoskeleton.
AB  - Shear stress is thought to be important in maintaining vascular homeostasis and
      regulating vascular remodeling. The authors have previously shown that low shear
      stress increases interleukin (IL)-8 gene expression in endothelial cells.
      However, the detailed events that contribute to the regulation of this expression
      remain to be identified. In this study, the authors examined whether the shear
      stress-induced IL-8 mRNA expression in endothelial cells is mechanotransduced by
      integrins and the cytoskeleton. Exposure of endothelial cells to low shear stress
      (4.2 dyne/cm(2)) rapidly increased the expression of IL-8 mRNA. The induced IL-8
      mRNA expression was inhibited by GRGDNP, which blocked the binding of integrins
      to the extracellular matrix. Additionally, this increase was attenuated by both
      anti-alpha(v)beta(3) integrin and anti-beta(1) integrin antibodies. Treatment of
      endothelial cells with either low shear stress or cytochalasin D resulted in the
      disruption of the cytoskeleton. Following the disruption of filamentous F-actin,
      the IL-8 mRNA expression in endothelial cells also increased, indicating that the
      shear stress-induced IL-8 mRNA expression may be mediated by the disruption of
      actin fibers. Taken together, these data suggest that integrins and the actin
      cytoskeleton play important roles in regulating the shear stress-induced IL-8
      gene expression. Supplementary materials are available for the Materials and
      Methods section of this article. Go to the publisher's online of edition of
      Endothelium for this free supplemental resource.

PMID- 18080865
TI  - Role of ligand-specific integrins in endothelial cell alignment and elongation
      induced by cyclic strain.
AB  - Ligand-specific integrins are thought to play a critical role in regulating
      multiple biological processes. However, the mechanisms by which ligand-specific
      integrins mediate external stimuli and activate intracellular signaling pathways
      remain to be elucidated. The aim of this study was to clarify the role of ligand
      specific integrins in the morphological changes induced by cyclic strain (CS) via
      the p38 mitogen-activated protein kinase (p38 MAPK) pathway. Endothelial cells
      (ECs) were cultured on collagen (a ligand for integrin alpha 2 beta1, but not for
      alpha 5 and beta 4)-coated flexible plates and incubated for 24 h with or without
      anti-alpha2 integrin antibody (anti-alpha2), anti-alpha5, anti-beta1, or anti
      beta4. ECs were then subjected to 15.6% average CS at 60 cycles/min up to 24 h.
      After exposure to CS, the cell shape index (defined as (4pi x cell area)/(cell
      perimeter)(2)), the cell orientation angle, and activation of p38 MAPK were
      assessed. ECs in the absence of integrin-blocking antibodies were elongated and
      aligned in response to CS. Anti-alpha 2 and anti-beta1 abolished both
      morphological changes of ECs as well as the activation of p38 MAPK. In contrast,
      anti-alpha 5 and anti-beta 4 inhibited neither morphological changes of ECs nor
      the activation of p38 MAPK. Our results indicate that ligand-specific integrins
      play a crucial role in the morphological changes of ECs induced by CS via the p38
      MAPK pathway.

PMID- 18080867
TI  - A novel methodology to probe endothelial differential gene expression profile
      reveals novel genes.
AB  - Endothelial dysfunction is a major feature of vascular diseases. A practical,
      minimally invasive method to effectively "probe" gene transcription for an
      individual patient's endothelium has potential to "customize" assessment for an
      individual at risk of vascular disease as well as pathophysiologic insight in an
      in vivo human, clinical context. Published literature lacks a methodology to
      identify endothelial differential gene expression in individuals with vascular
      disease. We describe a methodology to do so. The aim of this study was to
      specifically utilize (a) cutaneous microvascular biopsy, (b) laser capture
      microdissection, (c) cDNA amplification, (d) suppression subtractive
      hybridization, (e) high-throughput sequencing techniques, (f) real-time
      polymerase chain reaction (PCR), and (g) in combination of these methods, to
      profile differential gene expression in the context of cardiovascular and
      cerebrovascular disease. Endothelial cells were obtained by laser capture
      microdissection from a patient and a healthy sibling's microvascular biopsy
      tissues. Endothelial RNA was extracted, reverse transcribed, and amplified to ds
      cDNA. Suppression subtractive hybridization was used to establish an endothelial
      differential gene expression library. Real-time PCR confirmed SERP1, caspase 8,
      IGFBP7, S100A4, F85, and F147 up-regulation between 1.4- and 3.47-fold. The
      authors have successfully established a methodology to profile endothelial
      differential gene expression and identified six differentially expressed genes.
      This minimally invasive novel method has potential wide application in the
      customized assessment of many patients suffering vascular diseases.

PMID- 18080866
TI  - Transcriptome of angiopoietin 1-activated human umbilical vein endothelial cells.
AB  - Angiopoietin 1 (Ang-1) is the main ligand for endothelial cell-specific tyrosine
      kinase (Tie-2) receptors and it promotes migration and proliferation and inhibits
      apoptosis and vascular leakage. The exact mechanisms through which the Ang-1
      exerts these effects remain unclear. The authors exposed human umbilical vein
      endothelial cells (HUVECs) to Ang-1 (300 ng/mL) for 4 h and conducted gene
      expression profiling using oligonucleotide microarrays. Real-time polymerase
      chain reaction (PCR) was also conducted to verify several of the genes that were
      regulated by Ang-1. Exposure to Ang-1 resulted in induction of 86 genes that are
      involved in endothelial cell (EC) proliferation, differentiation, migration, and
      survival. Thirty-six of these genes, including stanniocalcin, cyclin D1, vascular
      endothelial growth factor C, fms-related tyrosine kinase 1, interleukin 8, and
      CXCR4 have previously been shown to be induced by vascular endothelial growth
      factor (VEGF), suggesting significant similarities between VEGF and Ang-1
      pathways. Ang-1 exposure also inhibited mRNA expressions of 49 genes, most of
      which are involved in cell cycle arrest, apoptosis, and suppression of
      transcription. These results indicate that Ang-1 triggers coordinated responses
      in endothelial cells designed to inhibit the expression of proapoptotic and
      antiproliferative genes and up-regulate proproliferative, proangiogenic, and
      antiapoptotic pathways. Moreover, we also found that the Erk1/2,
      phosphatidylinositol (PI) 3-kinase, and the mTOR pathways are involved in Ang-1
      induced gene expression in HUVECs.

PMID- 18080868
TI  - gamma-Aminbuturic acid A receptor mitigates homocysteine-induced endothelial cell
      permeability.
AB  - Many cerebrovascular disorders are accompanied by an increased homocysteine (Hcy)
      levels. We have previously shown that acute hyperhomocysteinemia (HHcy) leads to
      an increased microvascular permeability in the mouse brain. Hcy competitively
      binds to gamma -aminbuturic acid (GABA) receptors and may increase vascular
      permeability by acting as an excitatory neurotransmitter. However, the role of
      GABA-A (GABA(A)) receptor in Hcy-induced endothelial cell (EC) permeability
      remains unclear. In the present study we attempted to determine the role of
      GABA(A) receptor and the possible mechanisms involved in Hcy-induced EC layer
      permeability. Mouse aortic and brain ECs were grown in Transwells and treated
      with 50 mu M Hcy in the presence or absence of GABA(A)-specific agonist muscimol.
      Role of matrix metalloproteinase-9 (MMP-9) was determined using its activity
      inhibitor GM-6001. Involvement of extracellular signal-regulated kinase (ERK)
      signaling was assessed using its kinase activity inhibitors PD98059 or U0126. EC
      permeability to the known content of bovine serum albumin (BSA)-conjugated with
      Alexa Flour-488 was assessed by measuring fluorescence intensity of the solutes
      in the Transwell's lower chambers. It was found that Hcy induced the formation of
      filamentous actin (F-actin). Hcy-induced EC permeability to BSA was significantly
      decreased by GABA and muscimol treatments. Presence of MMP-9 or ERK kinase
      activity inhibitors restored the Hcy-induced EC permeability to its baseline
      level. The mediation BSA leakage through the ECs was further confirmed in the
      experiments where Hcy-induced alterations in transendothelial electrical
      resistance of confluent ECs were assessed. The data suggest that Hcy increases EC
      layer permeability through inhibition of GABA(A) receptor and F-actin formation,
      in part, by transducing ERK and MMP-9 activation.

PMID- 18080869
TI  - Both senescence and apoptosis induced by deprivation of growth factors were
      inhibited by a novel butyrolactone derivative through depressing integrin beta4
      in vascular endothelial cells.
AB  - Both senescence and apoptosis of vascular endothelial cells (VECs) are involved
      in the development of cardiovascular diseases, including atherosclerosis. To
      understand the association between senescence and apoptosis in vascular
      endothelial cells, the authors first explored whether senescence and apoptosis
      took place at the same time in human umbilical vein endothelial cells (HUVECs)
      deprived of the growth factors. Integrin beta4 is a key factor in HUVEC
      apoptosis, to know whether this integrin is implicated in VEC senescence, the
      authors checked the changes of integrin beta4 level during HUVEC aging. Then the
      authors investigated the effects of 3BDO (3-benzyl-5-((2-nitrophenoxy)methyl)
      dihydrofuran-2(3H)-one) on the senescence induced by deprivation of serum and
      fibroblast growth factor (FGF)-2. The results showed that deprivation of growth
      factors not only induced apoptosis, but also triggered senescence in HUVECs. The
      authors found that the level of integrin beta 4 was increased markedly during
      HUVEC senescence. 3BDO (20 to 60 microg/mL) could inhibit both senescence and
      apoptosis and depress integrin beta 4 level. The data suggested that integrin
      beta4 might be a pivotal factor in the relationship between senescence and
      apoptosis.

PMID- 18080870
TI  - Glutathione-S-transferase protects against oxidative injury of endothelial cell
      tight junctions.
AB  - Oxidative damage of endothelial tight junction permeability is involved in the
      pathophysiology of a variety of vascular diseases. The authors studied the role
      of the antioxidant enzyme, human glutathione-S-transferase A4-4 (hGSTA4-4), in
      regulating expression of major molecules of tight junction in vascular
      endothelial cells under oxidative stress induced by H(2)O(2). A vascular
      endothelial cell line, mouse pancreatic endothelial cells (MS1), was transduced
      with recombinant adenoviral vector containing hGSTA4-4 gene. hGSTA4-4 induced
      expression of tight junction proteins occludin and zonula occludens (ZO)-1 under
      oxidative stress. Increased hGSTA4-4 expression correlated with increased
      transepithelial electrical resistance and decreased tyrosine phosphorylation of
      occludin and ZO-1 following exposure to H(2)O(2). In addition, morphologic
      dissociation of occludin, ZO-1, and F-actin during oxidative stress was reduced
      in hGSTA4-4-expressing cells. To explore a genetic approach for vascular diseases
      associated with disruption of tight junction proteins, we introduced the same
      viral vector to blood vessels of mice, rats, and rabbits ex vivo and found strong
      expression of hGSTA4-4 in endothelial cells. These results demonstrate that
      oxidative stress mediated disruption of tight junctions in endothelial cells may
      be attenuated by hGSTA4-4 expression.

PMID- 18080871
TI  - Circulating precursor levels of endothelin-1 and adrenomedullin, two endothelium
      derived, counteracting substances, in sepsis.
AB  - Plasma levels of endothelin-1 (ET-1) and adrenomedullin (ADM), two opposingly
      acting peptides, correlate with mortality in endotoxemia, but their measurement
      is cumbersome. New sandwich assays have been introduced that measure more stable
      precursor fragments. The objective of this study was to investigate the
      counterplay of their precursor peptides in septic patients and to compare them
      with disease severity and other biomarkers. Blood samples of an observational
      study in 95 consecutive critically ill patients admitted to the intensive care
      unit (ICU) were analyzed. CT-proET-1 and MR-proADM concentrations on admission
      were measured using new sandwich immunoassays. Depending on the clinical severity
      of the infection, both CT-proET-1 and MR-proADM levels exhibited a gradual
      increase from Systemic Inflammatory Response Syndrome (SIRS) to sepsis and septic
      shock (p < .001). Compared to the group of survivors, the group of nonsurvivors
      had higher median values of MR-proADM (5.7 nmol/L [range 0.4 to 21.0] versus 1.9
      nmol/L [range 0.3 to 17.1], p < .02) and similar CT-proET-1 levels (56.0pmol/L
      [range 0.5 to 271.0] versus 54.1pmol/L [range 1.0 to 506.0], p = .86). Receiver
      operating characteristics (ROC) curve analysis showed a higher prognostic
      accuracy of the calculated ratio of both counteracting substances as compared to
      CT-proET-1 (p = 0.001) and C-reactive protein (CRP) (p = .001) and in the range
      of MR-proADM (p = .51), procalcitonin (p = 0.22), and the APACHE II score (p =
      .61). Endothelin-1 and adrenomedullin precursor peptides gradually increase with
      increasing severities of infection in critically ill patients. The ratio of the
      two counteracting peptides correlates with mortality and shows a prognostic
      accuracy to predict adverse outcome comparable to the APACHE II score.

PMID- 18080872
TI  - Hypoxia disturbs fetal hemodynamics and growth.
AB  - Low-birth-weight babies have an increased risk of cardiovascular disease (CVD) in
      later life. The authors hypothesize that fetal hypoxia alters the structure and
      function of the developing cardiovascular system resulting in CVD. They
      investigated the effects of chronic hypoxia on cardiac performance, hemodynamic
      control, and growth during the second half of embryonic chick development. Three
      stages of hemodynamic adaptations were identified in hypoxic chick embryos. At
      embryonic day 13 (E13), heart rate and blood pressure were higher in hypoxic
      embryos. At E17, this was followed by sympathetic hyperinnervation of peripheral
      arteries, resulting in increased vasoconstriction during a chemoreflex. This was
      accompanied by dilatation of the left ventricle and a 50% reduction in cardiac
      contractility. E19 hypoxic embryos had a 33% higher baseline vascular tone, but
      failed to maintain blood pressure during acute stress, indicating cardiac
      failure. Reduced body, heart, and liver weights followed the hemodynamic changes.
      Chronic hypoxia induces dilated cardiomyopathy and sympathetic hyperinnervation
      of the peripheral vasculature leading to aberrant fetal hemodynamics and fetal
      growth restriction. This study identifies that alterations in fetal hemodynamic
      regulation are in the causal pathway between disturbances in fetal environment,
      restricted fetal growth and CVD, and establishes fetal hypoxia as a novel risk
      factor for cardiovascular disease.

PMID- 18080873
TI  - Final report on the safety assessment of Ricinus Communis (Castor) Seed Oil,
      Hydrogenated Castor Oil, Glyceryl Ricinoleate, Glyceryl Ricinoleate SE,
      Ricinoleic Acid, Potassium Ricinoleate, Sodium Ricinoleate, Zinc Ricinoleate,
      Cetyl Ricinoleate, Ethyl Ricinoleate, Glycol Ricinoleate, Isopropyl Ricinoleate,
      Methyl Ricinoleate, and Octyldodecyl Ricinoleate.
AB  - The oil derived from the seed of the Ricinus communis plant and its primary
      constituent, Ricinoleic Acid, along with certain of its salts and esters function
      primarily as skin-conditioning agents, emulsion stabilizers, and surfactants in
      cosmetics, although other functions are described. Ricinus Communis (Castor) Seed
      Oil is the naming convention for castor oil used in cosmetics. It is produced by
      cold pressing the seeds and subsequent clarification of the oil by heat. Castor
      oil does not contain ricin because ricin does not partition into the oil. Castor
      oil and Glyceryl Ricinoleate absorb ultraviolet (UV) light, with a maximum
      absorbance at 270 nm. Castor oil and Hydrogenated Castor Oil reportedly were used
      in 769 and 202 cosmetic products, respectively, in 2002; fewer uses were reported
      for the other ingredients in this group. The highest reported use concentration
      (81%) for castor oil is associated with lipstick. Castor oil is classified by
      Food and Drug Administration (FDA) as generally recognized as safe and effective
      for use as a stimulant laxative. The Joint Food and Agriculture Organization
      (FAO)/World Health Organization (WHO) Expert Committee on Food Additives
      established an acceptable daily castor oil intake (for man) of 0 to 0.7 mg/kg
      body weight. Castor oil is hydrolyzed in the small intestine by pancreatic
      enzymes, leading to the release of glycerol and Ricinoleic Acid, although 3,6
      epoxyoctanedioic acid, 3,6-epoxydecanedioic acid, and 3,6-epoxydodecanedioic acid
      also appear to be metabolites. Castor oil and Ricinoleic Acid can enhance the
      transdermal penetration of other chemicals. Although chemically similar to
      prostaglandin E(1), Ricinoleic Acid did not have the same physiological
      properties. These ingredients are not acute toxicants, and a National Toxicology
      Program (NTP) subchronic oral toxicity study using castor oil at concentrations
      up to 10% in the diet of rats was not toxic. Other subchronic studies of castor
      oil produced similar findings. Undiluted castor oil produced minimal ocular
      toxicity in one study, but none in another. Undiluted castor oil was severely
      irritating to rabbit skin in one study, only slightly irritating in another,
      mildly irritating to guinea pig and rat skin, but not irritating to miniature
      swine skin. Ricinoleic Acid was nonirritating in mice and in one rabbit study,
      but produced well-defined erythema at abraded and intact skin sites in another
      rabbit study. Zinc Ricinoleate was not a sensitizer in guinea pigs. Neither
      castor oil nor Sodium Ricinoleate was genotoxic in bacterial or mammalian test
      systems. Ricinoleic Acid produced no neoplasms or hyperplasia in one mouse study
      and was not a tumor promoter in another mouse study, but did produce epidermal
      hyperplasia. Castor oil extract had a strong suppressive effect on S(180) body
      tumors and ARS ascites cancer in male Kunming mice. No dose-related reproductive
      toxicity was found in mice fed up to 10% castor oil for 13 weeks. Female rats
      injected intramuscularly with castor oil on the first day after estrus had
      suppressed ovarian folliculogenesis and anti-implantation and abortive effects.
      Castor oil used as a vehicle control in rats receiving subcutaneous injections
      had no effect on spermatogenesis. A methanol extract of Ricinus communis var.
      minor seeds (ether-soluble fraction) produced anti-implantation, anticonceptive,
      and estrogenic activity in rats and mice. Clinically, castor oil has been used to
      stimulate labor. Castor oil is not a significant skin irritant, sensitizer, or
      photosensitizer in human clinical tests, but patients with occupational
      dermatoses may have a positive reaction to castor oil or Ricinoleic Acid. The
      instillation of a castor oil solution into the eyes of nine patients resulted in
      mild and transient discomfort and minor epithelial changes. In another study
      involving 100 patients, the instillation of castor oil produced corneal
      epithelial cell death and continuity breaks in the epithelium. Because castor oil
      contains Ricinoleic Acid as the primary fatty acid group, the Cosmetic Ingredient
      Review (CIR) Expert Panel considered the safety test data on the oil broadly
      applicable to this entire group of cosmetic ingredients. The available data
      demonstrate few toxic effects. Although animal studies indicate no significant
      irritant or sensitization potential, positive reactions to Ricinoleic Acid in
      selected populations with identified dermatoses did suggest that sensitization
      reactions may be higher in that population. Overall, however, the clinical
      experience suggests that sensitization reactions are seen infrequently. In the
      absence of inhalation toxicity data on these ingredients, the Panel determined
      that these ingredients can be used safely in aerosolized cosmetic products
      because the particle sizes produced are not respirable. Overall, the CIR Expert
      Panel concluded that these cosmetic ingredients are safe in the practices of use
      and concentrations as described in this safety assessment.

PMID- 18080874
TI  - Final report on the amended safety assessment of Propyl Gallate.
AB  - Propyl Gallate is the n-propyl ester of gallic acid (3,4,5-trihydroxybenzoic
      acid). It is soluble in ethanol, ethyl ether, oil, lard, and aqueous solutions of
      polyethylene glycol (PEG) ethers of cetyl alcohol, but only slightly soluble in
      water. Propyl Gallate currently is used as an antioxidant in a reported 167
      cosmetic products at maximum concentrations of 0.1%. Propyl Gallate is a
      generally recognized as safe (GRAS) antioxidant to protect fats, oils, and fat
      containing food from rancidity that results from the formation of peroxides. Data
      on dermal absorption are not available, but Propyl Gallate is absorbed when
      ingested, then methylated, conjugated, and excreted in the urine. The biological
      activity of Propyl Gallate is consistent with its free-radical scavenging
      ability, with effects that include antimicrobial activity, enzyme inhibition,
      inhibition of biosynthetic processes, inhibition of the formation of
      nitrosamines, anesthesia, inhibition of neuromuscular response to chemicals,
      ionizing/ultraviolet (UV) radiation protection, chemoprotection, antimutagenesis,
      anticarcinogenesis and antitumorigenesis, antiteratogenesis, and
      anticariogenesis. Animal toxicity studies indicate that Propyl Gallate was
      slightly toxic when ingested, but no systemic effects were noted with dermal
      application. Propyl Gallate is a strong sensitizer when tested intradermally,
      less sensitizing when tested topically, and nonsensitizing topically at 0.1% in
      one study. In a second study, Propyl Gallate (15 mg dissolved in 8 ml vehicle)
      was sensitizing to guinea pigs. Acute eye irritation tests conducted on nine
      cosmetic formulations, each containing less than 1% Propyl Gallate, were
      negative. A phototoxicity study conducted on a cosmetic formulation containing
      0.003% Propyl Gallate determined that the product was not phototoxic to guinea
      pigs. In one study, female rats fed 0.5 g Propyl Gallate had substantially
      increased fetal resorption rates when compared to controls, but in four other
      studies, Propyl Gallate at doses up to 2.04 g/kg was nonteratogenic in rats,
      rabbits, mice, and hamsters. In clinical cumulative irritancy tests, Propyl
      Gallate was nonirritating at concentrations up to 10%. Patch tests at
      concentrations less than 1% yielded positive elicitation responses. Repeat-insult
      patch tests using cosmetic formulations with 0.003% Propyl Gallate produced no
      irritation or sensitization. Propyl Gallate at a concentration of 10% in alcohol
      was nonphototoxic in 25 subjects. Cosmetic formulations, each containing 0.003%
      Propyl Gallate, produced no signs of photosensitization or phototoxicity in a
      total of 371 subjects. Although Propyl Gallate is not a skin irritant in clinical
      tests, the available data demonstrate that it is a skin sensitizer and that it
      may be a sensitizer at lower concentrations than originally thought, i.e., at
      concentrations less than 1%. In actual practice, cosmetic formulations contain
      Propyl Gallate at concentrations up to 0.1% and usage has increased over the past
      20 years. In spite of the increased exposure associated with increased use, it is
      the clinical experience of the Panel that the use of Propyl Gallate in cosmetics
      has not resulted in sensitization reactions. Therefore, the Panel believes that a
      concentration limitation of 0.1% in cosmetics is necessary (given the evidence of
      sensitization at concentrations less than 1%) and sufficient (given that current
      products are not producing adverse reactions).

PMID- 18080876
TI  - Comparison between chicken and rabbit antibody based particle enhanced cystatin C
      reagents for immunoturbidimetry.
AB  - We have compared three commercial particle enhanced cystatin C reagents. One of
      the reagents utilizes chicken antibodies and the other two reagents are rabbit
      antibody based. We show that the chicken antibody based reagent yields a higher
      delta absorbance when reacting with the antigen. IgY coupled to latex particles
      show a strong scatter response even at high antigen concentrations in contrast to
      the steep decline in scatter previously reported for IgY antibodies in solution.
      The reagent also showed a low CV for duplicate samples. Laying hens thus seems as
      an interesting source of antibodies for particle-enhanced immunoassays.

PMID- 18080877
TI  - Development of a lateral flow assay for rapid detection of bovine antibody to
      Anaplasma marginale.
AB  - A rapid lateral flow assay for detection of bovine antibody to Anaplasma
      marginale was developed. The assay used a recombinant peptide of major surface
      protein 5 as the antigen and a monoclonal antibody specific for bovine IgG(1)
      conjugated with colloidal gold beads for detection. Serum and anticoagulated
      blood samples were obtained from cattle in an area where anaplasmosis was
      endemic. The samples were selected based on positive identification of the
      organism in blood smears. The unclotted blood samples were used for PCR
      determination of the presence of A. marginale while the sera were tested by a
      commercial competitive enzyme immunoassay (CELISA) and by the lateral flow assay
      (LFA). Similar samples, collected at a Canadian sales barn, were tested by the
      CELISA and LFA and 10% were tested by PCR for the presence of A. marginale
      nucleic acid. In addition, stored serum samples from a second endemic area were
      tested by CELISA and LFA. Of the 114 smear positive samples, all were positive by
      CELISA and LFA. All samples were also positive by PCR. Samples from Canadian
      sources (n=524) were negative in the CELISA but 11 sera gave false positive
      reactions in the LFA. All samples tested were PCR negative. Of 113 samples from
      herds with anaplasmosis, 53 were positive in the CELISA and 50 were LFA positive.

PMID- 18080878
TI  - Establishment and characterization of monoclonal and polyclonal antibodies
      against human intestinal fatty acid-binding protein (I-FABP) using synthetic
      regional peptides and recombinant I-FABP.
AB  - We have succeeded in raising highly specific anti-human intestinal fatty acid
      binding protein (I-FABP) monoclonal antibodies by immunizing animals with three
      synthetic regional peptides, i.e., the amino terminal (RP-1: N-acetylated 1-19
      cysteine), middle portion (RP-2: cysteinyl-91-107) and carboxylic terminal (RP-3:
      cysteinyl-121-131) regions of human I-FABP, and the whole I-FABP molecule as
      antigens. We also raised a polyclonal antibody by immunizing with a recombinant
      (r) I-FABP. To ascertain the specificity of these antibodies for human I-FABP,
      the immunological reactivity of each was examined by a binding assay using rI
      FABP, partially purified native I-FABP and related proteins such as liver-type
      (L)-FABP, heart-type (H)-FABP, as well as the regional peptides as reactants, and
      by Western blot analysis. In addition, the expression and distribution of I-FABP
      in the human gastrointestinal tract were investigated by an immunohistochemical
      technique using a carboxylic terminal region-specific monoclonal antibody, 8F9,
      and a polyclonal antibody, DN-R2. Our results indicated that both the monoclonal
      and polyclonal antibodies established in this study were highly specific for I
      FABP, but not for L-FABP and H-FABP. Especially, the monoclonal antibodies raised
      against the regional peptides, showed regional specificity for the I-FABP
      molecule. Immunoreactivity of I-FABP was demonstrated in the mucosal epithelium
      of the jejunum and ileum by immunohistochemical staining, and the
      immunoreactivity was based on the presence of the whole I-FABP molecule but not
      the presence of any precursors or degradation products containing a carboxylic
      terminal fragment. It is concluded that some of these monoclonal and polyclonal
      antibodies, such as 8F9, 4205, and DN-R2, will be suitable for use in research on
      the immunochemistry and clinical chemistry of I-FABP because those antibodies can
      recognize both types of native and denatured I-FABP. In order to detect I-FABP in
      blood samples, it is essential to use this type of antibody, reactive to native
      type of I-FABP. It is anticipated that, in the near future, such a method for
      measuring I-FABP will be developed as a useful tool for diagnosing intestinal
      ischemia by using some of these antibodies.

PMID- 18080879
TI  - Novel tools for functional analysis of CD11c: activation-specific, activation
      independent, and activating antibodies.
AB  - Functions and binding properties of four CD11c-specific mAbs are described here.
      The mAb 496B stimulated, while 496K inhibited ligand binding of CD11c. The
      stimulatory mAb, 496B, as well as the inhibitory mAbs BU15 and 496 K appear to
      act allosterically, as they do not bind the CD11c I domain. The mAb 3.9 bound
      preferentially to activated forms of CD11c and the binding was divalent cation
      dependent. CD11c binding to 3.9 recapitulates many of the integrin-ligand
      interactions. Our data suggest that 3.9 is a competitive antagonist, BU15 and
      496K are allosteric antagonists, and 496B is an allosteric agonist of CD11c.
      These mAbs provide a set of tools to study the functions of the dendritic cell
      marker, CD11c.

PMID- 18080880
TI  - Detection of Salmonella typhimurium in raw meats using in-house prepared
      monoclonal antibody coated magnetic beads and PCR assay of the fimA gene.
AB  - A method for detection of Salmonella Typhimurium in meat samples that uses in
      house monoclonal antibody (MAb) coated magnetic beads for immunomagnetic
      separation (IMS) associated with PCR amplification of the gene fimA was
      developed. An internal amplification control (IAC) of the PCR reaction was
      constructed. The fimA PCR has shown 100% sensitivity and specificity when tested
      with various bacteria. The detection limit of the IMS-PCR method, using a post
      enrichment in BHI broth for 6 h between IMS and PCR, was 1-10 CFU/mL. The method
      proved to be rapid (27 hrs), highly sensitive (1-10 CFU/25 g), and specific for
      detection of S. Typhimurium from experimentally contaminated pork and chicken
      meat samples.

PMID- 18080881
TI  - Label-free piezoelectric immunosensor for rapid assay of Escherichia coli.
AB  - A piezoelectric sensor with immobilized polyclonal antibody was developed as a
      label-free assay for the model bacterium, Escherichia coli. The polyclonal
      antibody was prepared from mice BALB/c and covalently immobilized on the sensing
      gold electrode of the piezoelectric quartz crystal. The biosensor was able to
      detect E. coli in the range of 10(6)-10(9) CFU/mL; signal of the negative control
      was not statistically relevant in the selected range. Samples could be analyzed
      in four minutes and one measuring cycle including regeneration was completed
      within ten minutes. Repeatability of the developed method is discussed; the
      signal obtained from three different biosensors was 12.9+/-0.4 Hz for the sample
      containing 10(8) CFU/mL.

PMID- 18080882
TI  - Antigen heterologous enzyme linked immunosorbent assay for the measurement of
      estrone-3-glucuronide.
AB  - We report a novel antigen heterologous enzyme linked immunosorbent assay for the
      direct estimation of estrone-3-glucuronide (E1-3-G) in diluted human urine. The
      differential behavior of antibody towards the labeled and unlabelled analyte in
      heterologous systems forms the basis of the present assay. Antiserum was raised
      in New Zealand white rabbits using estrone-3-glucuronide-bovine serum albumin (E1
      3-G-BSA) as immunogen and nandrolone-17-HS (N-17-HS) coupled to horseradish
      peroxidase (HRP) with and without urea bridge ((N-17-HS-Urea-HRP/N-17-HS-HRP) as
      an enzyme labeled reagent. To the E1-3-G antibody coated wells, 50 microL
      standard or appropriately diluted (1:20) female urine samples were added along
      with nandrolone-17-HS-HRP/N-17-HS-Urea-HRP conjugate (100 microL) and were
      incubated at room temperature (RT) for 1 hour. Bound enzyme activity was measured
      by using tetramethyl benzidine/hydrogen peroxide (TMB/H(2)O(2)) as substrate. The
      cross-reaction of E1-3-G antiserum with C(18), C(19), C(21), C(27) steroids was
      less than 0.1% in both assays. Incorporation of urea bridge in the enzyme
      conjugate has decreased the effective displacement dose, i.e., ED(50) from 20
      ng/ml to as low as 2 ng/mL. The sensitivity of the assay using N-17-HS-HRP and N
      17-HS-Urea-HRP was 0.6 ng/mL and 0.4 ng/mL, respectively. The intra-assay and
      inter-assay coefficient of variation (CVs) ranged from 4.7-9.0% and 5.1-6.4%,
      respectively. The estrone glucuronide level was also determined in female urine
      samples of 26 and 28 days cycle depicting a prominent peak corresponding to the
      preovulatory phase. The urinary E1-3-G values correlated well with those obtained
      by heat denaturation of urine samples r=0.94 (n=27).

PMID- 18080883
TI  - Establishment of hybrid cell lines producing monoclonal antibodies to a synthetic
      peptide from the E1 region of the hepatitis C virus.
AB  - We aimed at establishing hybridoma cells secreting monoclonal antibodies (mAbs)
      against E1 synthetic peptide of HCV. BALB/c mice were immunized with HCV E1
      synthetic peptide (GHRMAWDMM) and its spleenocytes were fused with the P3NS1
      myeloma cell line. Two highly reactive and specific mAbs (10C7 IgG2b mAb, and
      10B2 IgG1 mAb) were generated. The target HCV E1 antigen was identified at
      approximately 38 kDa in serum of infected individuals. A newly developed ELISA
      detected the target antigen in 90% of sera from HCV RNA infected individuals with
      a specificity of 84%. So, the generated mAbs may provide promising probes for
      serodiagnosis of HCV infection.

PMID- 18080886
TI  - Proceedings of the Network for Environmental Risk Assessment and Management
      (NERAM) IV Colloquium. Cuernavaca, Mexico.

PMID- 18080884
TI  - Kosmotropes enhance the yield of antibody purified by affinity chromatography
      using immobilized bacterial immunoglobulin binding proteins.
AB  - The yield of antibody purified using affinity chromatography on immobilized
      Protein A or Protein G was increased up to 5-fold (500%) by including kosmotropic
      salts in the binding buffer. The binding buffer is used to equilibrate the
      affinity column before applying a sample to the column and also to dilute the
      sample prior to loading onto the affinity column to optimize conditions for a
      maximal binding of antibodies to affinity gels. In this study, the kosmotropic
      salts that were effective in greatly increasing antibody binding to Protein A
      included both inorganic and organic salts of ammonium; sodium; or potassium
      sulfate, phosphate, polycarboxylates; for example, succinate, citrate,
      isocitrate, N-(2-hydroxyethylene diamine triacetate (HEDTA), ethylene diamine
      tetraacetate (EDTA), and ethylene glycol-O,O'-bis(2-aminoethyl)-N,N,N'N'-tetra
      acetate(EGTA). On an equal-molar basis, the greater the number of carboxylic
      groups within the polycarboxylate molecule, the greater the increase in the yield
      of the purified antibody that was observed. The data show that kosmotropes can be
      used as effective additives to enhance the binding of immunoglobulins to Protein
      A or Protein G gels with a resultant increase in the yield of the purified
      antibodies. Thus, it appears that strongly hydrated anions (citrate, sulfate, and
      phosphate) and weakly hydrated cations (ammonium, potassium) increase the yield
      of antibody purified on either Protein A or Protein G affinity gels.

PMID- 18080887
TI  - International perspectives on air quality: risk management principles for policy
      development--conference statement.
AB  - This statement is the result of discussions held at the 2005 NERAM IV Colloquium
      "International Perspectives on Air Quality: Risk Management Principles for Policy
      Development" and represents the collective views of 35 delegates, including
      international air quality policy analysts, academics, nongovernmental
      organizations, industry representatives, and decision makers from Mexico, Canada,
      the United States, the United Kingdom, Brazil, Hong Kong, and The Netherlands on
      principles for global air quality management. The objective of the colloquium was
      to "establish principles for air quality management based on the identification
      of international best practice in air quality policy development and
      implementation." This statement represents the main findings of a breakout group
      discussion session, presentations of an international panel of speakers from
      Canada, the United States, Mexico, and Hong Kong and views of the delegates
      expressed in plenary discussions. NERAM undertook a transparent process to try to
      ensure that the statement would accurately reflect the conference discussions,
      including documenting the proceedings and inviting delegates' comments on draft
      versions of the statement.

PMID- 18080888
TI  - Air quality risk management.
AB  - Rather than attempt to provide a comprehensive account of air quality risk
      assessment, as might be found in a textbook or manual, this article discusses
      some issues that are of current importance in the United Kingdom and the rest of
      Europe, with special emphasis on risk assessment in the context of policy
      formulation, and emerging scientific knowledge. There are two pollutants of
      particular concern and that both pose challenges for risk assessment and policy,
      and they are particulate matter (PM) and ozone. The article describes some issues
      for health risk assessment and finally some forward-looking suggestions for
      future approaches to air quality management.

PMID- 18080890
TI  - Air quality risk assessment and management.
AB  - This article provides (1) a synthesis of the literature on the linkages between
      air pollution and human health, (2) an overview of quality management approaches
      in Canada, the United States, and the European Union (EU), and (3) future
      directions for air quality research. Numerous studies examining short-term
      effects of air pollution show significant associations between ambient levels of
      particulate matter (PM) and other air pollutants and increases in premature
      mortality and hospitalizations for cardiovascular and respiratory illnesses.
      Several well-designed epidemiological studies confirmed the adverse long-term
      effects of PM on both mortality and morbidity. Epidemiological studies also
      document significant associations between ozone (O3), sulfur (SO2), and nitrogen
      oxides (NO(x)) and adverse health outcomes; however, the effects of gaseous
      pollutants are less well documented. Subpopulations that are more susceptible to
      air pollution include children, the elderly, those with cardiorespiratory
      disease, and socioeconomically deprived individuals. Canada-wide standards for
      ambient air concentrations of PM2.5 and O3 were set in 2000, providing air
      quality targets to be achieved by 2010. In the United States, the Clean Air Act
      provides the framework for the establishment and review of National Ambient Air
      Quality Standards for criteria air pollutants and the establishment of emissions
      standards for hazardous air pollutants. The 1996 European Union's enactment of
      the Framework Directive for Air Quality established the process for setting
      Europe-wide limit values for a series of pollutants. The Clean Air for Europe
      program was established by the European Union to review existing limit values,
      emission ceilings, and abatement protocols, as set out in the current
      legislation. These initiatives serve as the legislative framework for air quality
      management in North America and Europe.

PMID- 18080889
TI  - Challenges to managing air pollution.
AB  - There is never enough money, time, or resources to do all the things that need to
      be done--a statement that is true both for governments and individuals. For
      governments, this fact implies that (1) priorities need to be established; (2)
      goals are essential to be set to address these priorities, partly with an eye
      toward maximizing the net benefits to society; and (3) policies need to be
      implemented to reach those goals efficiently and effectively. In this article,
      major challenges of managing air pollution in each of these areas are examined.

PMID- 18080891
TI  - Meeting the future challenges of air quality management in the United States.
AB  - The U.S. Clean Air Act (CAA, or the Act) and its amendments has achieved
      substantial progress in cleaning up the nation's air. Over the past 30 years, the
      CAA reduced emissions of the 6 principal ("criteria") pollutants by over 25%,
      even while gross domestic product (GDP) has increased over 150% and population
      and energy consumption rose by nearly 40%. However, despite the tremendous gains
      the Act has brought, the country's air quality management (AQM) system still
      faces substantial challenges. In response to a congressional request for an
      independent evaluation of the overall effectiveness of the CAA, the National
      Research Council formed the Committee on Air Quality Management. Composed of 25
      members with diverse areas of air quality expertise, the committee was charged
      with developing scientific and technical recommendations for strengthening the
      nation's AQM system. In 2004, the National Academies published their
      recommendations in a text entitled Air Quality Management in the United States
      (National Research Council, 2004).

PMID- 18080892
TI  - Principles for air quality management: an environmental nongovernment
      organization (ENGO) perspective.
AB  - Over the past 10-15 years there have been many positive developments in
      environmental policy that have resulted in reductions in air pollutant emissions
      in Canada. This article presents an environmental nongovernmental organization
      (ENGO) perspective on air quality management policy initiatives at various levels
      in Canada, including a discussion of gaps, barriers, and opportunities for future
      integrated policy solutions to address both air quality and climate change.

PMID- 18080893
TI  - WHO Air Quality Guidelines for Europe.
AB  - This article describes the WHO Air Quality Guidelines and highlights two projects
      that were initiated to update the risk assessment of the main air pollutants:
      "Systematic Review of Health Aspects of Air Quality in Europe" and the "Global
      Update of WHO Air Quality Guidelines." The report of the Systematic Review
      emphasizes that the accumulated evidence is sufficient to require actions
      reducing the health impacts of air pollution in Europe. The global update of the
      air quality guidelines focuses on particulate matter (PM), ozone, NO2, and SO2
      and addresses issues associated with the practical feasibility of attaining the
      guidelines in developing countries. The article illustrates WHO's activities
      toward gathering the best available international scientific evidence to support
      air quality policy development in all regions of the world.

PMID- 18080894
TI  - Impacts of the Convention on Long-range Transboundary Air Pollution on air
      quality in Europe.
AB  - The Convention on Long-range Transboundary Air Pollution has been one of the main
      ways of protecting the environment in Europe from air pollution. This convention
      has successfully bridged different political systems even through times of
      political change, and is a prime example of what can be achieved through
      intergovernmental cooperation. Through creating an effective framework for
      controlling and reducing the damage to human health and the environment from
      transboundary air pollution, this convention has proved successful. This article
      considers the development of the convention and its work on adverse air pollution
      effects, in particular on activities related to quantifying effects on human
      health as carried out by the convention's joint (with WHO) Task Force on the
      Health Effects of Air Pollution (Task Force on Health), and concludes with some
      indications of the convention's future priorities.

PMID- 18080895
TI  - Air quality management in Mexico.
AB  - Several significant program and policy measures have been implemented in Mexico
      over the past 15 yr to improve air quality. This article provides an overview of
      air quality management strategies in Mexico, including (1) policy initiatives
      such as vehicle use restrictions, air quality standards, vehicle emissions, and
      fuel quality standards, and (2) supporting programs including establishment of a
      national emission inventory, an air pollution episodes program, and the
      implementation of exposure and health effects studies. Trends in air pollution
      episodes and ambient air pollutant concentrations are described.

PMID- 18080896
TI  - U.S. air quality management: local, regional and global approaches.
AB  - The purpose of this article is to review approaches to air quality management
      (AQM) in the United States. To characterize AQM in the United States, four
      examples that addressed local, regional, and global scale air pollution are
      described. These examples include: (1) the Hazardous Air Pollutants (HAPs)
      program, (2) National Ambient Air Quality Standards (NAAQS) program, (3) "Cap &
      Trade" programs, and (4) U.S. global pollution control efforts. These four
      examples were chosen because each presents a different approach to AQM. This was
      not intended to be a comprehensive description of U.S. AQM programs, but rather
      representative of selected examples that highlight the themes of this program.
      Some general principles that are illustrated in the article and are considered
      important characteristics of U.S. AQM are: Ensure open access to information and
      transparency in decision making. Develop and sustain a well-trained workforce.
      Facilitate training, networking, and technology transfer among air quality
      managers. Integrate planning and coordination of efforts across jurisdictions
      (across federal, state, and local agencies). Educate and encourage participation
      of stakeholders. Balance of societal benefits and costs. Apply innovative
      approaches, where possible. Fund research to improve the scientific basis for
      problem identification and effective AQM strategy development.

PMID- 18080897
TI  - Canada-wide standards and innovative transboundary air quality initiatives.
AB  - Canada's approach to air quality management is one that has brought with it
      opportunities for the development of unique approaches to risk management. Even
      with Canada's relatively low levels of pollution, science has demonstrated
      clearly that air quality and ecosystem improvements are worthwhile. To achieve
      change and address air quality in Canada, Canadian governments work together
      since, under the constitution, they share responsibility for the environment. At
      the same time, because air pollution knows no boundaries, working with the
      governments of other nations is essential to get results. International
      cooperation at all levels provides opportunities with potential for real change.
      Cooperation within transboundary airsheds is proving a fruitful source of
      innovative opportunities to reduce cross-border barriers to air quality
      improvements. In relation to the NERAM Colloquium objective to establish
      principles for air quality management based on the identification of
      international best practice in air quality policy development and implementation,
      Canada has developed, both at home and with the United States, interesting air
      management strategies and initiatives from which certain lessons may be taken
      that could be useful in other countries with similar situations. In particular,
      the Canada-wide strategies for smog and acid rain were developed by Canadian
      governments, strategies that improve and protect air quality at home, while
      Canada-U.S. transboundary airshed projects provide examples of international
      initiatives to improve air quality.

PMID- 18080898
TI  - Development of a health effects-based priority ranking system for air emissions
      reductions from oil refineries in Canada.
AB  - In Canada, the Canadian Council of Ministers for the Environment (CCME) is
      currently engaged in a process to determine how best to reduce air emissions from
      oil refineries. The National Framework for Petroleum Refineries Emissions
      Reduction (NFPRER) is being developed with the input of stakeholders, including
      nongovernment organizations (NGOs), industry, and regulatory jurisdictions. One
      component of this framework is the development of a tool to prioritize emissions
      for reduction based on estimated health impacts. HEIDI II (Health Effects
      Indicators Decision Index II) is a spreadsheet-based model that prioritizes a
      series of carcinogenic and noncarcinogenic air toxicicants and criteria air
      contaminants commonly emitted from Canadian oil refineries. A generic
      meteorological dispersion model was applied to reported annual emissions data for
      each of Canada's 20 refineries. Photodegradation rates and ambient levels of each
      substance were accounted for, and air concentrations were calculated for 20
      geographic zones around each refinery. These were coupled to toxicity data
      derived mainly from Health Canada and the U.S. Environmental Protection Agency
      (EPA), and applied to target populations of children, adults and seniors. HEIDI
      II predicts incidence of relevant disease endpoints from each substance emitted,
      except for benzene, toluene, ethylbenzene, and xylene (BTEX) and polycyclic
      aromatic hydrocarbons (PAH), which were treated as chemical mixtures. Rankings
      were based on predicted case incidence or the application of a common health
      impact metric, disability-adjusted life years (DALYs), to the predicted
      incidence. Using the DALY approach, priority rankings can be made within each of
      the chemical classes, or across all three classes together. HEIDI II incorporates
      several switches that allow the user to investigate alternate scenarios based on
      stack height, average daily sunlight hours (for calculating photodegradation),
      and the possibility of emissions below regulatory reporting thresholds.

PMID- 18080899
TI  - Evaluation and identification of priority air pollutants for environmental
      management on the basis of risk analysis in Russia.
AB  - Since 1997, more than 30 health-risk analyses were conducted using Russian data
      sets. These studies demonstrated that air pollution is the most important
      environmental contributor toward morbidity and mortality risk in Russia, with 90%
      of the total human health risk coming from the criteria pollutants total
      suspended particulate (TSP), SO2, and NO(x). This article contributes to the
      ongoing discussion of the magnitude of this health issue in Russia by providing
      an estimate of both the mortality rate attributed to airborne pollutants and the
      associated economic damages. The 90% confidence interval of mortality is 46,000
      132,000, and the associated economic damages are between 2.6 and 6.5% of gross
      domestic product (GDP). The largest source of uncertainty in mortality is the
      concentration-response parameter, accounting for 50-60% of the total variability
      in the estimate. The point estimate of 87,000 implies that mortality due to
      airborne pollutants is threefold higher than reported due to tuberculosis,
      twofold due to transportation accidents, and about the same as that from suicide
      and homicide combined. By 2002 there was enough evidence regarding potential
      health hazard and air pollution exposure in Russia to start environmental
      management reform. In 2004 Russia officially adopted guidelines for health risk
      analysis associated with air pollution. The next step is to use this health-risk
      assessment approach as a lead for sensible reforms of the emissions-permit system
      and environmental finance.

PMID- 18080900
TI  - Toxicological effects of in utero and lactational exposure of rats to a mixture
      of environmental contaminants detected in Canadian Arctic human populations.
AB  - As part of the program to investigate mixture effects of environmental
      pollutants, this study describes clinical, biochemical, and histopathological
      effects in rats perinatally exposed to a mixture of persistent organochlorine
      pollutants and methylmercury that simulates the blood contaminant profile of
      humans residing in the Canadian Arctic. Groups of pregnant rats were administered
      orally 0, 0.05, 0.5, or 5 mg/kg body weight (bw)/d of a reconstituted mixture of
      organochlorine pollutants (referred to as mixture hereafter) from gestational day
      (GD) 1 to postnatal day (PND) 23. Positive and vehicle controls were given
      Aroclor 1254 (Aroclor hereafter, 15 mg/kg bw) and corn oil (vehicle),
      respectively. After parturition, the pups were colled to 8 per litter on PND 4,
      and killed on PND 35, 77, or 350, when tissues were collected for analysis.
      Gestational and lactational exposure of rats to mixture up to 5 mg/kg bw produced
      adverse effects in the offspring, including growth suppression, decreased spleen
      and thymic weights, increased serum cholesterol and liver microsomal enzyme
      activities, lower liver retinoid levels, and histological changes in the liver,
      thyroid, and spleen. Histological changes in the liver consisted of hepatic
      inflammation, vacuolation, and hypertrophy, while alterations in the thyroid were
      characterized by hypertrophy and hyperplasia of follicles. The hepatic and
      thyroidal effects were mild even at the highest dose. The spleen showed a dose
      dependent atrophy in the lymphoid nodules and periarteriolar lymphatic sheath
      regions. Aroclor produced effects similar to those seen in the highest mixture
      group. In summary, this study demonstrates that exposure to the reconstituted
      mixture at 5 mg/kg bw produced growth suppression, changes in organ weights, and
      biochemical and histopathological changes in liver, thyroid, and spleen. This
      study also demonstrated that the blood level in rats given the 5-mg/kg dose,
      where most of the effects were observed, is 100-fold higher than the blood level
      in the 0.05-mg/kg group, which is comparable to that found in humans living in
      the Canadian Arctic region.

PMID- 18080901
TI  - Biomonitoring recycled water in the Santa Ana River Basin in southern California.
AB  - The Santa Ana River (SAR) is the primary source of groundwater recharge for the
      Orange County Groundwater Basin in coastal southern California. Approximately 85%
      base flow in the SAR originates from wastewater treatment plants operated by
      three dischargers. An on-line, flow-through bioassay using Japanese medaka
      (Oryzias latipes) as a means of judging potential public health impacts was
      employed to evaluate the water quality of the surface water and shallow
      groundwater originating from the SAR. Three chronic (3-4.5 mo) exposures using
      orange-red (outbred, OR) and see-through (color mutant, ST-II) Japanese medaka as
      bioindicators were conducted to evaluate endocrinologic, reproductive, and
      morphologic endpoints. No statistically significant differences in gross
      morphological endpoints, mortality, gender ratios, and vitellogenin induction
      were observed in fish from SAR groundwater treatment compared to the group tested
      in solute reconstituted reverse osmosis-treated or granular activated carbon
      (GAC)-treated control waters. Significant differences were observed in egg
      reproduction and the time to hatch in SAR groundwater; however, total
      hatchability was not significantly lower. To evaluate the estrogenic activity of
      the surfacewater source of the groundwater, SAR surface water was evaluated for
      vitellogenin and gonadal histopathology in juvenile medaka with no effects
      observed. These results demonstrate that OR Japanese medaka may be a sensitive
      strain as an on-line monitor to predict potential impacts of water quality, but
      further studies are needed to elicit causative agents within the water mixture.

PMID- 18080902
TI  - Imidacloprid induces neurobehavioral deficits and increases expression of glial
      fibrillary acidic protein in the motor cortex and hippocampus in offspring rats
      following in utero exposure.
AB  - Imidacloprid, a neonicotinoid, is one of the fastest growing insecticides in use
      worldwide because of its selectivity for insects. The potential for neurotoxicity
      following in utero exposure to imidacloprid is not known. Timed pregnant Sprague
      Dawley rats (300-350 g) on d 9 of gestation were treated with a single
      intraperitoneal injection (i.p.) of imidacloprid (337 mg/kg, 0.75 x LD50, in corn
      oil). Control rats were treated with corn oil. On postnatal day (PND) 30, all
      male and female offspring were evaluated for (a) acetylcholinesterase (AChE) and
      butyrylcholinesterase (BuChE) activity, (b) ligand binding for nicotinic
      acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (m2
      mAChR), (c) sensorimotor performance (inclined plane, beam-walking, and forepaw
      grip), and (d) pathological alterations in the brain (using cresyl violet and
      glial fibrillary acidic protein [GFAP] immunostaining). The offspring of treated
      mothers exhibited significant sensorimotor impairments at PND 30 during
      behavioral assessments. These changes were associated with increased AChE
      activity in the midbrain, cortex and brainstem (125-145% increase) and in plasma
      (125% increase). Ligand binding densities for [3H]cytosine for alpha4beta2 type
      nAchR did not show any significant change, whereas [3H]AFDX 384, a ligand for
      m2mAChR, was significantly increased in the cortex of offspring (120-155%
      increase) of imidacloprid-treated mothers. Histopathological evaluation using
      cresyl violet staining did not show any alteration in surviving neurons in
      various brain regions. On the other hand, there was a rise in GFAP immunostaining
      in motor cortex layer III, CA1, CA3, and the dentate gyrus subfield of the
      hippocampus of offspring of imidacloprid-treated mothers. The results indicate
      that gestational exposure to a single large, nonlethal, dose of imidacloprid
      produces significant neurobehavioral deficits and an increased expression of GFAP
      in several brain regions of the offspring on PND 30, corresponding to a human
      early adolescent age. These changes may have long-term adverse health effects in
      the offspring.

PMID- 18080903
TI  - Exposure of developing chicks to perfluorooctanoic acid induces defects in
      prehatch and early posthatch development.
AB  - There is increasing concern over the widespread use of perfluorinated chemicals,
      which accumulate in various tissues and penetrate the mammalian fetus. A chick
      model was established for the rapid evaluation of teratogenicity of these
      chemicals, an important issue because developmental defects often occur at lower
      exposures than those required for adult systemic toxicity. Chicken eggs were
      injected with varying doses of perfluorooctanoic acid prior to incubation.
      Observed were defects in hatching, increased incidence of splayed legs, and
      interference with the appropriate development of yellow plumage. All these
      defects are potentially related to essential molecular/biochemical and functional
      development of the chick. Because of the relationship between structural defects
      and vulnerability of the developing brain, our model points to the need to
      evaluate neurobehavioral teratogenicity, which may involve even lower doses.

PMID- 18080904
TI  - Chronic exposure of Rana pipiens tadpoles to UVB radiation and the estrogenic
      chemical 4-tert-octylphenol.
AB  - While adverse effects of exposure to ultraviolet B radiation (UVBR) and
      environmental pollutants on amphibians have been documented, few studies examined
      the effects of interactions between environmental stressors on amphibian health.
      Here the impacts of chronic exposure to UVBR and the estrogenic chemical 4-tert
      octylphenol (OP), alone and in combination, on the survival, development, growth,
      and metamorphosis of Rana pipiens (northern leopard frog) tadpoles are evaluated.
      Tadpoles were exposed to environmentally relevant levels of OP (0.01 or 10 nM),
      with and without exposure to UVBR (approximately 0.22 W/m2). After 8 mo of
      exposure, animals were transferred to a clean-water grow-out system for 3
      additional mo. There was no effect of treatments on the weights of animals at wk
      42 or on the age, snout-vent length (SVL), and weights of tadpoles at forelimb
      emergence (FLE). However, tadpoles exposed to UVBR had markedly delayed
      development and significantly fewer reached metamorphosis compared to control
      animals. Although exposure to UVBR and OP together produced the highest incidence
      of mortality and developmental anomalies, UVBR alone was sufficient to produce
      significant mortality of tadpoles, and exposure to UVBR or OP alone induced a
      significant increase in malformations and abnormalities. The malformations
      observed consisted mainly of spinal curvature. Our results show that chronic
      exposure to environmental levels of UVBR or OP alone exerts lethal and/or
      sublethal effects on R. pipiens tadpoles.

PMID- 18080905
TI  - Re: M. B. Forrester and R. D. Merz (2006), Comparison of trends in gastroschisis
      and prenatal illicit drug use rates. J. Toxicol. Environ. Health A 69:1253-1259.

PMID- 18080906
TI  - Manganese peroxidase production by immobilized Phanerochaete chrysosporium BKM-F
      1767 in a cell bioreactor.
AB  - Manganese-dependent peroxidase (MnP) production was performed in an immobilized
      cell bioreactor in which Phanerochaete chrysosporium BKM-F-1767 was immobilized
      on polystyrene foam. The immobilized cell culture yielded significantly greater
      MnP activity than the conventional stationary liquid culture. Cultivation was
      carried out in batch mode; the effect of glucose concentration was investigated
      and growth kinetics parameters were found as, micromax=0.59 day(-1), Ks=0.33 g/L
      and Kss=14.5. Batch operation led to maximum MnP (770.82 U/L) in the culture
      medium containing 0.05% Tween 80, 10 g/L glucose, and 174 microM Mn2+ at 37
      degrees C and pH 4.5. Enzyme productivity was obtained as 110.12 U/day/L.

PMID- 18080907
TI  - Comparison of some properties of free and immobilized alpha-amylase by
      Aspergillus sclerotiorum in calcium alginate gel beads.
AB  - Some properties of immobilized alpha-amylase by Aspergillus sclerotiorum within
      calcium alginate gel beads were investigated and compared with soluble enzyme.
      Optimum pH and temperature were found to be 5.0 and 40 degrees C, respectively,
      for both soluble and immobilized enzymes. The immobilized enzyme had a better Km
      value, but kcat/Km values were the same for both enzymes. Entrapment within
      calcium alginate gel beads improved, remarkably, the thermal and storage
      stability of alpha-amylase. The half life values of immobilized enzyme and
      soluble enzyme at 60 degrees C were 164.2, and 26.2 min, respectively. The
      midpoint of thermal inactivation (Tm) shifted from 56 degrees C (for soluble
      enzyme) to 65.4 degrees C for immobilized enzyme. The percentages of soluble
      starch hydrolysis for soluble and immobilized alpha-amylase were determined to be
      97.5 and 92.2% for 60 min, respectively.

PMID- 18080908
TI  - Synthesis of the human insulin gene: protein expression, scaling up and
      bioactivity.
AB  - Optimized Synthetic human insulin gene was preferred to easy of cloning, plasmid
      stability, and protein expression away from the native sequence and its rare
      codons. Two steps to obtain the insulin, so we assembled the gene of 293 bp using
      a battery of overlapped synthetic oligos, then cloned into pET101directional TOPO
      expression vector downstream to the T7 promoter. The proinsulin products were
      produced as inclusion bodies in E. coli at a level of 10%. The batch cultivation
      of the strain yielded 6 g/L, while the high cell density of fed-batch cultivation
      yielded 46 g/L. The proinsulin purification yielded 110 mg/gram cell weight, and
      1.3 mg/gram of a bioactive insulin. The native insulin was generated by enzymatic
      conversion of chemically processed proinsulin. The produced insulin was matched
      with that of a commercial aqueous version at a level of enzyme immunoassys, SDS
      PAGE, RP-HPLC, and bioactivity. The present results showed that the produced
      insulin has a comparable biochemical and potency similar to that of commercial
      one.

PMID- 18080909
TI  - PCR of immobilized DNA molecules isolated from human blood cells by a non
      enzymatic method.
AB  - DNA molecules suitable for amplification by Polymerase Chain Reaction were
      obtained by immobilizing whole blood or isolated leukocytes and incubating the
      immobilized cells for one hour with the known non-enzymatic solution described
      for preparing intact DNA molecules for PFGE. Cell immobilization was done in
      agarose gels and punches of 1.2 mm of diameter had the amount of DNA needed for
      amplifying chromosomal and mitochondrial sequences, many times. The approach was
      successfully used in preparing DNA molecules from multiple samples in flat-bottom
      96-well ELISA plates. The procedure is simple and does not demand special
      conditions for sample transportation or conservation; thus, it should be useful
      to collect and process samples under field conditions in epidemiological studies.

PMID- 18080910
TI  - Two biosensors for phenolic compounds based on mushroom (Agaricus bisporus)
      homogenate: comparison in terms of some important parameters of the biosensors.
AB  - Interest in molecular imprinted polymer techniques has increased because they
      allows for the improvement of some stability characteristics of enzymes. The high
      stability of molecularly imprinted enzymes for a substrate can make them ideal
      alternatives as recognition elements for sensors. A bioimprinted mushroom tissue
      homogenate biosensor was constructed in a very simple way. For this purpose,
      sulfite was used. The enzyme, polyphenol oxidase, was first complexed by using a
      competitive inhibitor, sulfite, in aqueous medium and then the enzyme was
      immobilized on gelatin by crosslinking with glutaraldehyde on a glass electrode
      surface. Similarly, polyphenol oxidase uncomplexed with sulfite was also
      immobilized on a glass electrode in the same conditions. The aim of the study was
      to compare the two biosensors in terms of their repeatability and thermal, pH,
      and operational stability; also, the linear ranges of the two biosensors were
      compared with each other.

PMID- 18080911
TI  - Effect of immobilization on kinetic and thermodynamic characteristics of sulfide
      oxidase from Arthrobacter species.
AB  - In order to determine the impact of immobilization on biocatalytic efficacy of
      sulfide oxidase, the kinetic and thermodynamic properties of native and DEAE
      cellulose immobilized sulfide oxidase from Arthrobacter species FR-3 were
      evaluated. Immobilization increased the catalytic efficiency of sulfide oxidase
      by producing a lower Michaelis-Menten constant (Km) and a higher rate of
      catalysis (Vmax) at different temperatures. The first-order kinetic analysis of
      thermal denaturation demonstrated that the values of enthalpy (delta H*d) and
      entropy (delta S*d) of immobilized sulfide oxidase were lower than the native
      enzyme, confirming the thermal stabilization of sulfide oxidase by
      immobilization. The delta H*d and delta S*d of the immobilized enzyme at 35
      degrees C were 138.07 kJ/mol and 122.04 J/K/mol, respectively. These results
      suggest that immobilization made the sulfide oxidase from Arthrobacter sp. FR-3
      thermodynamically more efficient for catalysis of sulfide oxidation.

PMID- 18080912
TI  - Overexpression, effective renaturation, and bioactivity of novel single-chain
      antibodies against TNF-alpha.
AB  - Neutralization of tumor necrosis factor-alpha (TNF-alpha) has become an effective
      therapeutic strategy for TNF-related autoimmune diseases. Due to the limitations
      of the large molecular inhibitors in the therapy, development of novel TNF-alpha
      inhibitors is very attractive and useful. In this study, based on the previously
      designed domain antibody, two novel human anti-TNF single-chain antibodies were
      constructed using modular consensus frameworks of human antibody as scaffold to
      display the antagonistic peptides. A variety of expression plasmids were used to
      determine the optimal expression system. The single-chain antibodies were always
      overexpressed in E.coli BL21(DE3) host as inclusion bodies. Under the optimized
      refolding conditions, the inclusion bodies were renatured successfully and the
      refolded single-chain antibodies could bind with TNF-alpha and block TNF-induced
      cytotoxicity on L929 cells. The bioactivity of the single-chain antibodies was
      significantly increased over the domain antibody.

PMID- 18080913
TI  - Total RNA-isolation of abdominal hernia of rats for quantitative real-time
      reverse transcription (RT) PCR assays.
AB  - Increasing complications in incisional hernia surgery call for novel treatments.
      A gene expression analysis of injured tissues displays important parameters for
      tissue regeneration. Until today, no reliable method has been described for a
      quantitative gene expression analysis of hernia tissues. In this work, a protocol
      is described for the isolation of DNA-free total RNA of incisional hernias for
      the first time. Moreover, real-time RT PCR assays for collagen type I and III and
      TGF-beta1 are demonstrated for relative gene expression analyses. Both methods
      enable relative gene expression analyses of hernia tissues for the first time.

PMID- 18080914
TI  - Purification of monomeric prolactin charge isoform from buffalo pituitaries.
AB  - A standard protocol for isolation of buffalo prolactin (buPRL) was modified at
      the alcohol precipitation step. This modification could separate lower molecular
      weight prolactin from the higher molecular weight prolactin (PRL). Reloading the
      prolactin onto a Sephacryl S-200 gel purified the buPRL monomer. The purity of
      buPRL monomer was confirmed by 15% SDS PAGE. The buPRL monomer was >90% pure. It
      was characterized by specific anti-buPRL serum in ELISA and Western blot. A
      native PAGE of the PRL showed three charge isoforms. A protocol was standardized
      to separate prolactin monomeric least acidic isoforms using an anion exchanger.

PMID- 18080915
TI  - Praseodymium methanesulfonate catalyzed one-pot synthesis of 3,4-dihydropyrimidin
      2-(1H)-ones.
AB  - A series of 3,4-dihydropyrimidin-2-(1H)-ones compounds was synthesized
      efficiently by a one-pot cyclocondensation of an aldehyde, 1,3-dicarbonyl
      compound, and urea in absolute ethanol under refluxing temperature using
      praseodymium methanesulfonate as catalyst. After the reaction, the catalyst can
      be easily recovered and reused several times without distinct decrease in
      reaction yields.

PMID- 18080916
TI  - One-pot solvent free synthesis and DNA binding studies of thieno[2,3-b]-1,8
      naphthyridines.
AB  - With the aim of evaluating interaction between double-stranded calf thymus
      (ds)DNA and sulphur containing fused planar rings, the derivatives of 1,8
      naphthyridine containing thiono groups were synthesized by the condensation of 2
      mercapto-3-formyl[1,8]naphthyridines using 1-chloroacetone, 2-chloroacetamide,
      chloroaceticacid, and 2-chloro-1-phenylethanone in the presence of anhydrous
      potassium carbonate as s catalyst under solvent free microwave irradiation. The
      structures of the compounds were elucidated on the basis of elemental analysis,
      IR, (1)H NMR, and mass spectra. The interaction of thieno[2,3-b]-1,8
      naphthyridine-2-carboxylic acid (TNC) (3a) with ct-DNA was studied by UV-Vis
      spectrophotometry, viscosity, thermal denaturation, as well as cyclic voltammetry
      experiments. On binding to DNA, the absorption spectrum underwent bathochromic
      and hypochromic shifts. Binding parameters, determined from spectrophotometric
      measurements indicated a binding constant of Kb=2.1 x 10(6) M(-1). The thieno[2,3
      b]-1,8-naphthyridine-2-carboxylic acid (3a) increases the viscosity of sonicated
      rod-like DNA fragments. The binding of TNC to DNA increased the melting
      temperature by about 4 degrees C. The decrease in peak current heights and shifts
      of peak potential values are observed by the addition of calf thymus DNA in
      cyclic voltammetry studies.

PMID- 18080917
TI  - The acute effect of oral ethanol intake on gastric myoelectrical activity in
      healthy volunteers.
AB  - The acute effect of ethanol intake on the upper gastrointestinal system is not
      clearly known. Animal studies have shown that ethanol inhibited the antral muscle
      fiber contractions and slow wave activity. BACKGROUND/AIMS: To show the acute
      effect of oral ethanol intake on gastric myoelectrical activity in healthy
      volunteers. METHODS: Fourteen healthy male volunteers were included in the study.
      They were given control solution with test meal and ethanol with test meal on two
      different days. Electrogastrography recordings were obtained in pre-/postprandial
      periods. RESULTS: On the days of ethanol intake, blood alcohol level reached
      above 80 mg/dl in 10 volunteers. Ethanol intake did not show any significant
      effect on any of the electrogastrography parameters. CONCLUSIONS: Though
      reasonable blood alcohol level was achieved and six volunteers experienced upper
      gastrointestinal system complaints, ethanol had no effect on gastric
      myoelectrical activity.

PMID- 18080918
TI  - Association between type 2 diabetes mellitus and Helicobacter pylori infection.
AB  - BACKGROUND/AIMS: It is well known that patients with diabetes mellitus are more
      prone to infection. In patients with diabetes mellitus, chronic infections are
      frequent and severe, due to the impairment of their immune status. The aim of
      this study was to determine the association between Helicobacter pylori infection
      and type 2 diabetes mellitus in the United Arab Emirates population. This is a
      case and control study comparison of type 2 diabetes mellitus and non-diabetic
      groups. The study was conducted at the primary health care clinics in United Arab
      Emirates during the period from June 2002 to August 2003. The study included 210
      type 2 diabetes mellitus patients and 210 non-diabetic subjects. METHODS:
      Helicobacter pylori was assessed by histopathological examination by measuring
      antibody profiles (IgG and IgA) among type 2 diabetes mellitus patients and the
      non-diabetic group. RESULTS: The mean age of type 2 diabetes mellitus patients
      infected with Helicobacter pylori was 48.1 +/- 7.9 years compared to 46.7 +/- 5.4
      years in the non-diabetic infected subjects. A positive antibody titer for
      Helicobacter pylori infection (IgA >or=300) was found in 76.7% of the diabetic
      subjects compared to 64.8% of the non-diabetic subjects (p<0.009). There was
      higher prevalence of Helicobacter pylori infection in diabetic obese patients
      than the non-diabetic subjects (23.6% vs 11.8%, p<0.001). Muscular (47.2%),
      gastrointestinal (29.8%), chronic bronchitis (22.4%), nausea (19.9%), anemia
      (18%), abdominal pain (12.4%), diarrhea (10.6%) and vomiting (7.5%) were more
      common in diabetic patients infected with Helicobacter pylori. CONCLUSIONS: The
      present study suggests that there is a significant association between
      Helicobacter pylori infection and type 2 diabetes mellitus. Helicobacter pylori
      infection was significantly higher in diabetic obese patients than non-diabetic
      subjects.

PMID- 18080919
TI  - Mucins in the colorectal neoplastic spectrum with reference to conventional and
      serrated adenomas.
AB  - BACKGROUND/AIMS: Alterations in expression of mucins and aberrant expression of
      various types of mucin genes were observed in colorectal adenomas and carcinomas,
      though their significance in neoplastic transformation of colorectal epithelium
      is yet to be determined. The aim of this study was to determine expression of
      MUC1, MUC2, MUC5AC, and MUC6 through conventional adenoma-carcinoma sequence and
      polyps involved in the "serrated" pathway of the colorectum using tissue array
      technique. METHODS: In this study, a total of 172 cases including 100 colorectal
      polyps [8 hyperplastic polyps, 10 sessile serrated adenomas, 19 tubular, 37
      tubulovillous, and 26 villous adenomas], 16 adenomas with intramucosal carcinoma,
      28 conventional colorectal cancers, and 28 normal mucosae were examined. Tissue
      array blocks were prepared and sections were stained immunohistochemically for
      MUC1, MUC2, MUC5AC, and MUC6. RESULTS: Expression of MUC1 significantly increased
      in close correlation with the neoplastic process and reached its highest values
      in intramucosal carcinomas and conventional colorectal cancers (p<0.001). In
      contrast, MUC2 expression showed a significant decrease in intramucosal carcinoma
      and conventional colorectal cancer groups (p<0.001). Sessile serrated adenomas
      exhibited the highest MUC5AC expression while adenomatous polyps showed an
      increase in MUC5AC expression in parallel with neoplastic progression (p<0.001).
      Hyperplastic polyps seemed to lie between normal mucosa and sessile serrated
      adenomas in terms of mucin expression, suggesting that they are morphologically
      and histogenetically linked. CONCLUSIONS: Upregulation of MUC1 and MUC6 through
      the adenoma-carcinoma sequence together with downregulation of MUC2 and MUC5AC at
      the neoplastic end of the spectrum seem to follow the steps of malignant
      transformation.

PMID- 18080920
TI  - Erythropoietin attenuates hydrogen peroxide-induced damage of hepatocytes.
AB  - BACKGROUND/AIMS: High levels of hydrogen peroxide (H2O2) are observed during
      inflammatory and ischemic states of the liver and usually lead to cellular
      dysfunction and cytotoxicity. Recently, it has been reported that erythropoietin
      and mitochondrial K (ATP) channel openers have a protective effect via a
      pharmacological preconditioning action during ischemia reperfusion injury of the
      liver and heart. However, it remains unclear as to whether K (ATP) channel
      blockers can reduce the protective effect of erythropoietin in the H2O2-induced
      injury of hepatocytes. METHODS: To determine whether erythropoietin treatment
      decreases H2O2-induced toxicity, we used human hepatocyte cell line Hep3B for
      assays. Cells were pretreated with different dosages of erythropoietin (0.1-1-10
      50 IU/ml) 2 h before H2O2 application. For determination of effects of blockage
      of mitochondrial K (ATP) channels during erythropoietin treatment, glibenclamide
      treatment was applied to the medium 2 h before H2O2 toxicity. Cell number,
      lactate dehydrogenase and caspase- 3 levels were measured in erythropoietin,
      glibenclamide and/or H2O2-treated groups. RESULTS: Erythropoietin treatment
      significantly increased cell number at the 24th and 48th h compared to the
      control group. H2O2 application induced apoptosis and lactate dehydrogenase
      release from Hep3B cells and decreased cell number. Erythropoietin prevents H2O2
      toxicity in hepatocytes. The K channel inhibitor glibenclamide decreased the
      cytoproliferative and cytoprotective effect of erythropoietin during H2O2
      toxicity of Hep3B cells. CONCLUSIONS: Erythropoietin treatment may be considered
      as a therapeutic agent during oxidative injuries of hepatocytes and its
      cytoprotective effect is abolished by glibenclamide.

PMID- 18080921
TI  - Serum insulin like growth factor-1 (IGF-1) and insulin like growth factor binding
      protein-3 (IGFBP-3) levels in liver cirrhosis.
AB  - BACKGROUND/AIMS: Impaired growth hormone-insulin like growth factor system in
      hepatic cirrhosis leads to cirrhosis-related complications. In this study, we
      aimed to investigate whether serum levels of insulin like growth factor-1 and
      insulin like growth factor binding protein-3 are related to the level of hepatic
      dysfunction, clinical grade, and etiologic factors of the disease in patients
      with liver cirrhosis. METHODS: Forty-two patients with liver cirrhosis who were
      diagnosed by means of clinical findings, endoscopy, imaging studies, or
      histopathology were enrolled in the study. An age- and sex-matched control group
      was comprised of 37 healthy controls with no signs of liver disease by clinical
      or laboratory findings. The demographic features (age, sex, height, and weight)
      and serum levels of liver function tests, urea, creatinine, sodium, potassium,
      insulin like growth factor-1, and insulin like growth factor binding protein- 3
      and hemogram values were recorded for each individual. The patients were grouped
      according to Child Pugh classification and etiology. RESULTS: Insulin like growth
      factor-1 and insulin like growth factor binding protein-3 levels were
      significantly lower in the cirrhotic group in comparison to the control group
      (p<0.005). A statistically significant decrease in levels of insulin like growth
      factor-1 and insulin like growth factor binding protein-3 was correlated with the
      degree of liver dysfunction, namely, lowest decrease in Child Pugh class A and
      highest decrease in class C. With respect to etiology, insulin like growth factor
      1 levels of alcohol-related liver cirrhosis were significantly lower than those
      of hepatitis B- related cirrhosis. There was no relation between insulin like
      growth factor binding protein-3 level and etiology. In the cirrhotic group,
      insulin like growth factor- 1 level was positively correlated with serum albumin
      and negatively correlated with serum creatinine and sodium levels and spleen
      size. Likewise, insulin like growth factor binding protein-3 level was positively
      correlated with serum albumin. There was a negative correlation between insulin
      like growth factor binding protein-3 level and serum bilirubin and spleen size.
      CONCLUSIONS: Insulin like growth factor-1 and insulin like growth factor binding
      protein-3 levels are related to the level of clinical impairment and were
      independent of the etiology. They may serve as novel markers of hepatocellular
      dysfunction.

PMID- 18080922
TI  - Takayasu's arteritis in a case diagnosed as Crohn's disease.
AB  - Takayasu's arteritis is a chronic granulomatous vasculitis of unknown etiology
      that primarily affects the great arteries; the aorta and its branches, and
      pulmonary and coronary arteries are the most commonly affected. Takayasu's
      arteritis and inflammatory bowel disease in the same individual has been
      occasionally reported in the literature. We report a case with Takayasu's
      arteritis and Crohn's disease.

PMID- 18080923
TI  - A rare cause of chronic abdominal pain, weight loss and anemia: abdominal
      actinomycosis.
AB  - Abdominal actinomycosis is a subacute/chronic bacterial infection that affects
      different body regions. A 46-year-old female presenting with intermittent
      abdominal pain, nausea, vomiting, transient bowel obstruction, weight loss (18
      kg), anemia, and hypoalbuminemia was evaluated in our clinic. Physical
      examination showed diffuse slight tenderness and a relatively fixed tender mass
      with ill-defined edges localized to the right lower quadrant. We did not make any
      specific diagnosis after complete laboratory, endoscopic and radiological
      investigations. We confirmed abdominal actinomycosis after explorative laparotomy
      and histopathological examination of biopsy specimen taken from the mesenterium
      and omentum. After long-term penicillin (6 months) treatment, significant
      clinical and laboratory improvement were observed. In conclusion, abdominal
      actinomycosis should be considered in the differential diagnosis of chronic
      inflammatory disease with mass lesion and intestinal obstruction.

PMID- 18080924
TI  - Acute uremia and intestinal obstruction due to a retroperitoneal hydatid cyst.
AB  - Hydatid disease should be considered in the differential diagnosis of any cystic
      mass in endemic areas. The symptoms due to bulk effect, usually occurring over a
      certain period of time, depend on the site and size of the cyst. We report an
      unusual presentation of retroperitoneal hydatid cyst with rapidly developing
      uremia and acute intestinal obstruction.

PMID- 18080925
TI  - Congenital pouch colon: is it really a rare pathology?
AB  - Congenital pouch colon is a condition of a shortened and pouch-like dilated colon
      and it is usually associated with an anorectal malformation. The pathogenesis and
      embryology of congenital pouch colon are not well understood, but dietary,
      environmental factors and familial inheritance may be contributing factors in
      this pathology. Most of the cases in the literature have been reported from
      India. This increased regional incidence may be attributed to the lack of
      awareness of this pathology or its mislabeling rather than regional distribution.
      Congenital pouch colon is classified into four types based on the length of the
      abnormal colon. A variable dilatation of the rectum and sigmoid is always present
      in anorectal malformation. However, there is no clear definition of a limit for
      the dilatation of the rectum and sigmoid observed in anorectal malformation.
      Furthermore, many surgeons do not routinely take a biopsy from a dilated rectum
      or sigmoid during a colostomy procedure in anorectal malformation cases. For
      these reasons, type IV congenital pouch colon can be easily underdiagnosed.
      Surgical treatment options in type IV congenital pouch colon include resection of
      the affected sites of the colon or excisional tapering coloplasty. In the
      undiagnosed cases, congenital pouch colon results in severe constipation and
      overflow incontinence. We herein report two additional new cases of type IV
      congenital pouch colon.

PMID- 18080926
TI  - Dieulafoy's lesion of the anal canal: report of a case.
AB  - BACKGROUND/AIMS: Dieulafoy's lesion of the anal canal is a very rare clinical
      case. Although it was first described in the stomach, there has been an
      increasing frequency, especially in the last decade, of reports of the lesion in
      the colorectal region. METHODS: Herein, we report one case presenting with
      massive hematochezia requiring multiple blood transfusions due to a Dieulafoy's
      lesion in the anal canal. To our knowledge, this is the fourth case in Medline.
      Surgical oversewing was attempted twice but rebleeding occurred, and local
      excision through the anal canal was performed. RESULTS: The patient was treated
      successfully with mucosectomy including the lesion. CONCLUSIONS: Sclerotherapy,
      alcohol and epinephrine injection, thermocoagulation and selective arterial
      embolization are the options of therapeutic endoscopy and interventional
      radiology. As for surgical management, oversewing is an alternative technique.
      However, in our opinion, because of the recurrent and life-threatening manner of
      this arterial bleeding pattern, local excision, if possible, is the most reliable
      management of the disease.

PMID- 18080927
TI  - Pegylated interferon treatment of acute pericarditis associated with acute
      hepatitis C.
AB  - A 65-year-old female patient was admitted to our hospital with the symptoms of
      chest pain, dyspnea and fatigue. She had undergone a tooth extraction three
      months before. She took no medication. Echocardiography revealed pericardial
      effusion. The serum alanine aminotransferase (ALT) at presentation was 650 IU/L
      and aspartate aminotransferase (AST) was 600 IU/L. Hepatitis C virus (HCV) RNA
      level was 150,000 IU/ml. Genotype was 1b. Acute pericarditis was considered to be
      caused by acute HCV infection. The patient was followed without treatment. One
      month later, AST and ALT were found as 65 IU/L and 82 IU/L, respectively; there
      were symptoms of effort dyspnea and fatigue. Echocardiography showed minimal
      decrease in pericardial effusion compared to one month previously. HCV RNA level
      was again checked and found as 155,000 IU/ml. The patient was given pegylated
      interferon. One month later, the pericardial effusion and related symptoms had
      disappeared. The pegylated interferon treatment was sustained for 24 weeks and
      HCV-RNA was found negative at the 3rd and 6th months of the treatment and six
      months after the end of treatment. We conclude that pegylated interferon may be
      offered to patients with symptomatic acute HCV-related pericarditis.

PMID- 18080928
TI  - Primary angiosarcoma of the spleen.
AB  - Primary angiosarcoma of the spleen is a rare neoplasm with a very poor prognosis.
      We present computed tomography and magnetic resonance imaging of a 49-year-old
      man with primary splenic angiosarcoma and liver metastasis. The literature on
      primary splenic angiosarcoma is reviewed and imaging variability of this rare
      tumor is discussed.

PMID- 18080929
TI  - [Patient surveys as an element of quality management in outpatient care:
      development and assessment of a questionnaire].
AB  - OBJECTIVE: The present study was designed to develop and assess a questionnaire
      measuring all relevant quality dimensions of general practice care from the
      patients' perspective. Furthermore, the study aimed to evaluate the
      implementation of a patient survey in outpatient care. METHODS: Based on the
      Kolner Patientenfragebogen (KPF) and by developing some additional new items, we
      created the new questionnaire KPF-A (Kolner Patientenfragebogen-ambulant) which
      covers all relevant aspects of outpatient care. The questionnaire was distributed
      to the patients of 41 GP's and specialists in ambulatory care from different
      regions of Germany. N=3188 patients were included in the sample. We used these
      data to assess some selected psychometric characteristics of the KPF-A. Factor
      analysis was used to examine the underlying factor structure. A qualitative study
      was conducted to evaluate the implementation of the patient survey. Therefore,
      all N=41 doctors involved were asked to complete five open questions concerning
      their experience. RESULTS: Most scales of the KPF-A showed good psychometric
      characteristics in the present study. Factor analysis revealed a two-factors
      solution for the new items representing the dimensions "professional competence"
      and "medical equipment". We have not yet been able to find a sound factor
      solution for those items representing the dimension "Staff and Organisation". The
      results of the qualitative study revealed a satisfying implementation of the
      patient survey in daily routine from the doctors' perspective. The length of the
      questionnaire was criticised by some participants. In the design of the study
      patients were supposed to fill in the questionnaires after consultation. This
      turned out to be difficult. We therefore modified the KPF-A so that patients can
      fill it in either before or after consultation.

PMID- 18080930
TI  - [Small-scale care by SHI physicians and their subjective choice of location
      within an oversupplied planning area].
AB  - OBJECTIVE: The aim of this study was to analyse whether geographical disparities
      exist in the outpatient care within the current planning districts of the German
      Association of SHI Physicians. Additionally, the motivation for the choice of a
      specific location by doctors was explored. METHODOLOGY: The study is based on two
      methods. Firstly on a geographical-statistical analysis of the ambulatory care in
      the study district (Rhein-Erft Distric), and secondly on a postal survey of the
      physicians. From a population of 619 physicians, 210 were chosen through a random
      sampling and sent a questionnaire. 117 physicians participated in the survey
      (rate of return: 55.7%). RESULTS: In the study district a considerable centre
      periphery difference exists when considering ambulatory care. Even though the
      planning district is adequately supplied according to the rules of the German
      Association of SHI Physicians, there are postcode areas that are undersupplied
      with physicians. Some of the observed geographical heterogeneities proved to be
      statistically significant. The postal survey has shown that there are a variety
      of factors determining the choice of location of physicians. It was not possible
      to determine whether economic factors play a greater role than soft site-related
      factors. CONCLUSION: The results of the study indicate that the current
      requirements of the German Association of SHI Physicians are insufficient to
      solve the problem of grographically equal ambulatory care. Taking into account
      that economic motives for choice of location are not significant for the
      physicians on their own, geographical disparities cannot be eliminated by
      financial incentives only.

PMID- 18080931
TI  - [Socioeconomic burden of hip fractures in Germany].
AB  - BACKGROUND AND OBJECTIVE: Treatment of hip fractures is a major challenge for the
      German health-care system due to the increasing incidence, high mortality rate,
      and need for long-term care. The purpose of this study was to determine the
      present and future economic burden of hip fractures in Germany. METHODS: Annual
      costs of hip fractures were determined from a societal perspective, by
      multiplying individual lifetime costs at different ages by the incidence of hip
      fractures (incidence-based cost-of-illness study). To calculate individual
      lifetime costs, a Markov decision model was developed. Secondary data were used.
      RESULTS: Total annual costs related to hip fractures were euro 2.77 billion. Due
      to population aging, costs of hip fractures may increase to euro 3.85 billion in
      2030. CONCLUSION: The result implies the need to identify effective prevention
      strategies for hip fractures and evaluate their cost-effectiveness.

PMID- 18080932
TI  - [Needs and wishes of healthy patients - how should physicians deal with them?].
AB  - BACKGROUND: It is hardly known how physicians feel and act if patients complain
      about social damage, familial tragedies or problems at work instead of illnesses
      or diseases. METHODS: Seven general practitioners discussed this subject in a
      focus-group setting. Within two hours, the three female and four male
      practitioners described some typical needs and wishes of their healthy patients.
      They were also encouraged to relate their feelings, reactions and behaviour as
      doctors. We interpreted the transcript of the recorded discussion according to
      the rules of a content-analysis. RESULTS: Certificates, (non-medical) advice and
      information, general care and reducing expenses are the main reasons for healthy
      patients to see them, the doctors quoted. The doctor's feelings depend on the
      personality of the patient and the reported problems. As a result, the
      physician's acceptance of needs and wishes of healthy patients varies over a
      broad spectrum and the decisions differ and seem arbitrary, although reporting on
      similar situations. Her/his personal attributes and mood mainly determine their
      decision about the patient's wishes. DISCUSSION: The question of whether to
      refuse or to respect healthy patients' wishes was arbitrary in this focus-group
      setting. Because no specific medical curriculum exists, rules for doctors'
      reactions and decisions on social, familial or working problems of their patients
      could be helpful. In particular, specific problems should be dealt with by social
      workers and related professions.

PMID- 18080933
TI  - [Do German nutrition interventions for children and adolescents meet quality
      criteria for program planning and evaluation? - Results of a survey of
      institutions at state and regional levels].
AB  - PURPOSE: The international literature describes comprehensive nutrition
      interventions for children and adolescents, and gives recommendations for
      successful program planning. For Germany, only few studies on these issues are
      available, and there is a particular scarcity of data on implementation,
      acceptance and effectiveness of nutrition interventions. Thus the aim of this
      study was to record nutrition interventions at state and regional levels in
      Germany, and to assess their project design and evaluation quality. On the basis
      of these data, conclusions about implementation, acceptance and effectiveness of
      interventions are made. METHODS: Quality indicators for project design, process
      and outcome evaluation were developed according to international literature and
      related quality assurance models. State ministries, public health departments,
      non-governmental institutions for health at state level and "Healthy Cities"
      (n=105) were surveyed about their nutrition interventions for children and
      adolescents including evaluation with a standardised questionnaire. The
      interventions were assessed using the developed quality criteria. RESULTS: The
      response rate was 70.5%. 42 primary preventive nutrition interventions were
      recorded. The quality criteria for program planning were only partly fulfilled.
      Encouraging results were, among others, that 54.8% of the projects combined
      behaviourally focused and environment focused criterions, 90.5% started in
      kindergarten or primary school, 88.1% involved parents, 85.7% cooperated with
      other institutions and 73.8% integrated nutrition specialists. 77.8% of the
      projects conducted a process evaluation (n=28), 60.7% of those had a good
      evaluation quality. Changing the environmental context proved to be the greatest
      challenge. The projects were well accepted by the target group. An outcome
      evaluation was conducted by 61.1% of the projects (n=22), 27.2% of those
      evaluations had a (very) good quality. Among these projects, 3 could improve
      nutrition knowledge, 3 environmental context and 3 nutrition behaviour.
      Improvements of medical parameters have not been recorded. CONCLUSION: In
      Germany, a high number of nutrition interventions for children and adolescents is
      being conducted. However, only five quality indicators were fulfilled by more
      than 75% of the projects. Because of inadequate evaluation quality, only little
      evidence for implementation, acceptance, and effectiveness could be found. More
      evaluation studies are needed to more successfully plan, implement and assess
      future interventions.

PMID- 18080934
TI  - [Variability of physician judgements in school entry examinations].
AB  - AIM: Data from school entry examinations were used for studying the variability
      of judgements between physicians performing the examinations. Two diagnoses were
      subject to examination: 1) Obesity, because an external criterion was available
      for this one. The medical classifications were compared with automated
      classifications using an external criterion. 2) Language anomalies, because these
      are the most frequent diagnoses. No external criterion had been available, thus
      differences within the group of examining physicians were considered. MATERIAL
      AND METHODS: Data from all school entry examinations performed in the city of
      Hannover between 1998 and 2001 were used. Altogether 14 physicians were involved,
      but due to low case numbers the data of two had to be omitted. The analyses are
      based on 18,303 datasets. For obesity the agreement rates between physicians' and
      automatically generated diagnoses were ascertained by calculating sensitivity and
      specificity. Comparisons of differences between physicians with respect to
      chances of getting a diagnosis were performed using logistic regression. RESULTS:
      The sensitivity of classifying body weights above the 75 (th) percentile
      correctly was 0.64 over all years of observation. The respective sensitivity of
      classifying children with body weights above the 97 (th) percentile was 0.70.
      Considerable differences over the four years of observation occurred. For
      performing logistic regressions, the diagnoses of the physician with the smallest
      difference from an external criterion were used as standard of comparison. The
      diagnoses of the physician with the largest difference yielded an OR=0.08. The
      overall variability within the group of examining physicians was large. With
      respect to language anomalies, although considerable, the within-group
      differences were smaller. The largest odds ratio in this case was OR=0.40.
      CONCLUSION: Diagnoses from school entry examinations vary according to the
      physicians involved. Thus the data should not be used for epidemiological
      studies. In order to improve data quality, the involved physicians should be
      extensively trained in using the instruments, and their instructions should be
      formulated more clearly in order to facilitate their application.

PMID- 18080935
TI  - [Health behaviour and health-risk behaviour among job-seekers: a screening at an
      employment agency].
AB  - AIM: The purpose of this study was to investigate the distribution of health
      behaviours and health-risk behaviours among three groups of job-seeking persons
      at employment agencies: short-term unemployed, long-term unemployed, and non
      unemployed (e.g., threatened by job loss) persons. A related aim was to identify
      the general willingness of persons recruited at employment agencies to
      participate in a study regarding health behaviours. METHOD: At the employment
      agency Greifswald (Western Pomerania, Germany), over a period of two weeks, all
      job-seeking persons while waiting were personally asked to participate in a
      screening regarding health behaviours. RESULTS: A total of 1672 persons (M=34
      years, 54% women), that is 74.3% of all job-seekers, participated in the
      screening. Regarding physical activity, fruit and vegetable intake, smoking, at
      risk drinking, drug use and overweight, all three groups showed a lack of health
      behaviour and increased risky behaviour compared to the general population or
      nation-wide guidelines. ANOVAs, chi (2) tests and logistic regressions showed
      significant differences among the three groups. Non-unemployed persons were more
      likely to report a healthier life style compared to both unemployed groups. Long
      term unemployed persons had a higher risk of smoking (OR=1.56; CI 95%=1.14-2.12)
      and of using drugs (OR=2.79; CI 95%=1.30-5.98) compared to short-term unemployed
      persons. CONCLUSIONS: The high participation rate, along with the high rates of
      risky behaviour and lack of health behaviour indicate the demand for intervention
      programs for job-seekers and the opportunity of using this setting for proactive
      interventions that could reach more than 70% of all job-seekers.

PMID- 18080936
TI  - [Modelling of the costs of productivity losses due to smoking in Germany for the
      year 2005].
AB  - PURPOSE: The aim of this study was to estimate disease-related productivity costs
      attributable to smoking in the year 2005 in Germany. METHODS: The calculation was
      based on the updated relative smoking-related disease risk found in the US Cancer
      Prevention Study II combined with data on smoking prevalence for Germany. With
      this, smoking-attributable cases resulting in premature mortality, invalidity,
      and temporal disability to work could be estimated. Neoplasms, diseases of the
      circulatory and the respiratory systems as well as health problems in children
      younger than one year were considered in the analysis. The human capital approach
      was applied to calculate years of potential work loss and productivity costs as a
      result of smoking. Various sensitivity analyses were conducted to test for
      robustness of the underlying model. RESULTS: Based on the assumptions within the
      model, 107,389 deaths, 14,112 invalidity cases, and 1.19 million cases of
      temporary disability to work were found to be due to smoking in 2005 in Germany,
      respectively. As a result, productivity costs of 9.6 billion were caused by
      smoking. CONCLUSIONS: The model showed that smoking has a high financial effect.
      Even so, further analyses are necessary to estimate an overall impact of smoking
      on the German society.

PMID- 18080940
TI  - Dopamine and serotonin interactions in the prefrontal cortex: insights on
      antipsychotic drugs and their mechanism of action.
AB  - Diminished activity within the prefrontal cortex (PFC) has been associated with
      many of the cognitive deficits that are observed in schizophrenia. It has been
      hypothesized that antipsychotic drugs (APDs) used to treat schizophrenia restore
      normal activity by antagonizing the dopamine (DA) D2 receptor, which is also
      known to modulate key ionic currents in the PFC. However, the hypothesis that an
      under-active cortical DA system is responsible for schizophrenic symptoms has
      been challenged by evidence that newer atypical APDs are weak antagonists at the
      D2 receptor but potent antagonists at the serotonin (5-HT) 2A receptor . This
      review examines how DA and 5-HT modulate cortical activity and how they may
      interact in ways that are relevant to schizophrenia. It is concluded that
      although D2 receptor antagonism remains a critical factor in restoring impaired
      cortical activity, effects on 5-HT receptors may act in a synergistic manner on
      NMDA and GABA currents to potentiate antipsychotic actions in the PFC.

PMID- 18080946
TI  - Gating deficits in model networks: a path to schizophrenia?
AB  - Gating deficits and hallucinatory sensations are prominent symptoms of
      schizophrenia. Comparing these abnormalities with the failure modes of network
      models is an interesting way to explore how they arise. We present a network
      model that can both propagate and gate signals. The model exhibits effects
      reminiscent of clinically observed pathologies when the balance between
      excitation and inhibition that it requires is not properly maintained.

PMID- 18080949
TI  - Physiological and neuromuscular responses of competitive cyclists during a
      simulated self-paced interval training session.
AB  - Responses of twelve competitive cyclists performing an interval training session,
      consisting of three successive 10-min self-paced exercise bouts separated by two
      15-min active recovery periods, were studied. Power output (PO), heart rate,
      pedaling cadence, ventilatory variables, overall ratings of perceived exertion
      (RPE) and electromyographic (EMG) activity of the vastus lateralis, vastus
      medialis, biceps femoris and medial hamstrings were recorded during each exercise
      bout. Mean PO (p<0.05) decreased significantly across the self-paced bouts, while
      RPE (p<0.01) increased significantly. PO and EMG activity did not show
      significant changes between the 3rd and 9th minute of each self-paced bout. Every
      self-paced bout showed an oxygen uptake (VO(2)) slow component between the 3rd
      and 9th minute and there was no effect of bout order on the magnitude of the
      VO(2) slow component. This study reveals that during an interval training
      session, moderately trained competitive cyclists are able to repeat three 10-min
      self-paced exercise bouts with only a slight decrease in PO (approximately 3%)
      and by maintaining unchanged physiological and neuromuscular responses. Moreover,
      the VO(2) slow component during each exercise bout was not related to changes in
      muscle activity, as every exercise bout was performed at a muscular work steady
      state with a constant PO.

PMID- 18080950
TI  - Heart rate responses at onset of contraction.
AB  - We tested the hypothesis that the initial heart rate (HR) response at the onset
      of maximal handgrip contraction is altered after training. 17 volunteers (nine
      trained and eight controls) performed ten intermittent static handgrip
      contractions with maximal effort, alternating between 15-s contractions and 15-s
      pauses. High-intensity static handgrip training was performed using the
      nondominant arm alone for 4 weeks. Handgrip force (HGF) and HR were analyzed for
      the initial 7 s of every static handgrip exercise. Peak HR (pre-training: 94.5 +/
      12.8 beats/min; post-training: 89.7 +/- 10.2 beats/min, p < 0.05) decreased.
      However, the magnitude of HR change at the onset of contraction remained constant
      (pre-training: 23.0 +/- 7.7 beats/min; post-training: 25.7 +/- 6.5 beats/min, p =
      0.0767), while the HR responses in the subsequent bouts increased after training
      (p < 0.001). The resting HR decreased (pre-training: 71.5 +/- 9.3 beats/min; post
      training 64.1 +/- 5.7 beats/min, p < 0.05). Maximal HGF increased by 11.1 % in
      trained arms and by 8.7 % in untrained arms, although an increase in maximal
      forearm girth was only observed in the trained arm (2.0 %, p < 0.0001). Although
      high-intensity training modulated the abrupt HR responses, the magnitude of the
      response remained unchanged at the onset of maximal forearm contraction and the
      resting HR significantly decreased.

PMID- 18080951
TI  - Sprint vs. interval training in football.
AB  - The aim of this study was to compare the effects of high-intensity aerobic
      interval and repeated-sprint ability (RSA) training on aerobic and anaerobic
      physiological variables in male football players. Forty-two participants were
      randomly assigned to either the interval training group (ITG, 4 x 4 min running
      at 90 - 95 % of HRmax; n = 21) or repeated-sprint training group (RSG, 3 x 6
      maximal shuttle sprints of 40 m; n = 21). The following outcomes were measured at
      baseline and after 7 weeks of training: maximum oxygen uptake, respiratory
      compensation point, football-specific endurance (Yo-Yo Intermittent Recovery
      Test, YYIRT), 10-m sprint time, jump height and power, and RSA. Significant group
      x time interaction was found for YYIRT (p = 0.003) with RSG showing greater
      improvement (from 1917 +/- 439 to 2455 +/- 488 m) than ITG (from 1846 +/- 329 to
      2077 +/- 300 m). Similarly, a significant interaction was found in RSA mean time
      (p = 0.006) with only the RSG group showing an improvement after training (from
      7.53 +/- 0.21 to 7.37 +/- 0.17 s). No other group x time interactions were found.
      Significant pre-post changes were found for absolute and relative maximum oxygen
      uptake and respiratory compensation point (p < 0.05). These findings suggest that
      the RSA training protocol used in this study can be an effective training
      strategy for inducing aerobic and football-specific training adaptations.

PMID- 18080952
TI  - Erythropoietin induces a shift of muscle phenotype from fast glycolytic to slow
      oxidative.
AB  - Sedentary and trained rat groups were studied. Each of these groups was either
      erythropoietin or placebo treated. Erythropoietin treatment increased
      significantly all haematological parameters studied. Training per se failed to
      modify haematological parameters. In a second time, we studied the specific
      activity of several oxidative enzymes in three different muscles. In sedentary
      rats, erythropoietin treatment increased significantly the specific activities of
      cytochrome c oxidase and L-3-hydroxyacyl CoA dehydrogenase in the soleus and
      those of L-3-hydroxyacyl CoA dehydrogenase and phosphofructokinase in both
      locomotor muscles. Training increased the oxidative enzymes activities in all
      muscles studied. In trained rats, effects of erythropoietin and training on
      oxidative enzymes activities were additive. In all erythropoietin treated
      muscles, the expression of slow twitch myosin light chains and oxidative myosin
      heavy chains increased. A similar phenomenon took place in all trained groups for
      light chains and in placebo treated trained rats for heavy chains. In trained
      groups, the effects of the hormone and of training were additive. Our results
      suggest strongly that two different mechanisms are involved in the response of
      skeletal muscles to erythropoietin treatment and to endurance training and
      probably whole body endurance is affected by erythropoietin treatment by an
      increase of oxygenation of all tissues.

PMID- 18080953
TI  - Trend in sports injuries among young people in Finland.
AB  - The main purpose of this study was to explore how the number of home, sports, and
      other leisure time injuries among young people aged 15 - 25 years has developed
      in Finland in 1988 - 2003. In 1988, 2559 people aged 15 - 25 years were
      interviewed by Statistics Finland. In 1993, 1997 and 2003 those amounts were 751,
      1638 and 1382. The subjects were asked in a telephone interview to report the
      injuries in which they had been involved during the previous 12 months. The crude
      injury incidence in 2003 was 364 per 1000 person years in men and 246 in women.
      The total number of injuries increased 49 % between the years 1988 and 2003. The
      number of sports injuries increased the most. The increase was greater among men
      than women, and the injury rate was higher among both men and women aged 15 - 19
      years than those aged 20 - 25 years. More research is needed on whether and how
      exercise and time at home have changed and become riskier among young people. It
      is also essential to find out which prevention methods are the most effective
      among young people and implement these measures in a well-planned and targeted
      manner.

PMID- 18080954
TI  - Capacity building in medical education and health outcomes in developing
      countries: the missing link.
AB  - BACKGROUND: Finding evidence for the link between capacity building in medical
      education and improved health outcomes in developing countries is an important
      challenge. We describe the Foundation for Advancement of International Medical
      Education and Research (FAIMER) Institute, a two year, part-time fellowship in
      medical education methodology and leadership and its evaluation as a model to
      bridge this gap by collecting quantitative and qualitative data on intermediary
      outcomes. METHODS: FAIMER has used the following framework of human capacity
      building programs: 1) identify young and talented individuals with potential to
      become agents for change; 2) organize and deliver an effective learning
      intervention that is relevant for the environment; 3) facilitate the opportunity
      for real-life application of acquired knowledge and skills with support; and 4)
      promote development of a sustainable career path with opportunities for growth
      and advancement. RESULTS: Twenty-three percent of curriculum innovation projects
      were directly related to community health. Of the 35 fellows in the first three
      classes of the Institute, there have been 11 promotions, 9 peer-reviewed
      publications and 14 international poster presentations, indicating development of
      the medical education field. Other qualitative and quantitative program
      evaluation data are presented. DISCUSSION: The link between capacity building in
      medical education and improved health can be demonstrated in several ways: align
      curriculum with local health needs, place learners in community clinical
      settings, teach basic healthcare workers, become involved in national policy
      development and develop the field of medical education. CONCLUSION: While
      experimental models may not be possible to evaluate the effect of capacity
      building, methods described may help support the connection between improved
      medical education and health.

PMID- 18080955
TI  - Understanding diversity as a framework for improving student throughput.
AB  - INTRODUCTION: Literature suggests that a diverse body of healthcare graduates
      could extend health service delivery. However, the literature also indicates that
      the throughput of minority, working class, and historically disadvantaged
      students is problematic. Poor throughput is attributed to the way that university
      environments alienate some students. This brief communication highlights lessons
      learned from exploratory interviews with four first-year oral hygiene students at
      a university in South Africa. It provides insight into the issues that contribute
      to academic success and failure. METHODS: Semi-structured, individual interviews,
      to gain information regarding students' university academic experiences were
      conducted. Enablers and barriers to learning identified in the literature were
      used to capture themes. FINDINGS: The following three themes emerged: educational
      identity, language and finances. The analysis showed how a white middle class
      student recognized practices that are rewarded at university and how three,
      working-class, black students experienced tension between their expectations and
      experiences and the university culture. However, far from being victims, these
      students provided suggestions on how their transition might be facilitated.
      CONCLUSION: Evidence suggests that these students wanted both to be apprenticed
      into the new way of doing things while having their differences acknowledged. A
      model for education that initiates learners and also challenges the culture of
      power is suggested.

PMID- 18080956
TI  - Exploring language barriers to Evidence-based Health Care (EBHC) in post-graduate
      medical students: a randomised trial.
AB  - BACKGROUND: Understanding the written English language might be a barrier when
      teaching Evidence-based Health Care (EBHC) to Spanish-speaking physicians. AIM:
      To quantify the magnitude of this potential barrier. METHOD: Cochrane Review
      abstracts in English or in Spanish were randomly distributed among first-year
      residents at the Pontificia Universidad Catolica of Chile. Residents answered
      investigator-designed questionnaires to measure their comprehension while the
      time needed to complete the task was recorded. RESULTS: Groups were similar at
      baseline. Mean score for those reading in Spanish was 11.9 +/- 2.8 (range 5 to
      18) compared to 10.5 +/- 3.8 (range 1 to 17) for those reading in English
      (p=0.04). Low scores ( pound 9) were twice as frequent for the English group than
      for the Spanish group (16.7% vs 34.7%; p=0.042). The time to complete the task
      was also longer for the group reading in English. CONCLUSION: Language should be
      taken into account when teaching EBHC to Spanish-speaking physicians.

PMID- 18080957
TI  - E-learning education solutions for caregivers in long-term care (LTC) facilities:
      new possibilities.
AB  - CONTEXT: Online learning (referred to as e-learning throughout this article) has
      proved to be a useful tool for delivering accessible and convenient education to
      busy clinical healthcare workers. The ABS Management Company specifically
      designed a program to provide nurses and caregivers with the necessary knowledge
      and skills to improve the quality of care and the quality of life for the
      geriatric population in long-term care (LTC) facilities. OBJECTIVES: The purpose
      of the "Online Solutions: Quality Education for Quality Care in Long-Term Care"
      program is to use new educational pedagogies and innovative ways to conceptualise
      and deliver healthcare education to meet the complex issues and concerns of
      caregivers in LTC facilities. METHODS: During the one-year period that data were
      collected for this study, 881 caregivers completed the eight (one-hour) modules
      in the program. Of these, 753 (85%) completed the optional assessment (both the
      pre and post tests) for one or more of the eight modules. Therefore, of the 881
      employees who reviewed all eight modules (881x8 = 7048 modules), 1046 modules
      (15%) had both pre-post test data upon which to build the analysis. FINDINGS:
      Information from the evaluation revealed learner improvement in pre-post test
      scores in excess of 10%, suggesting an increase in new and relevant skills and
      knowledge related to abuse and neglect, elopement, infection control, nutrition
      and hydration, pressure ulcers, provision of basic care and restraints. Moreover,
      the data indicated a reduction in the use of restraints and occurrence of
      pressure ulcers, suggesting that learners applied new knowledge and skills in the
      workplace. Finally, staff turnover rates decreased more than 20% suggesting
      greater job satisfaction after participating in the program. CONCLUSIONS: The
      research findings point to an urgent and unmet need to provide more accessible
      just-in-time, just-for-you education programs for caregivers in LTC facilities to
      ensure quality and efficient services to residents and their families.

PMID- 18080958
TI  - Partnering to enhance interprofessional service-learning innovations and
      addictions recovery.
AB  - CONTEXT: Service-learning programs are reported to benefit students, faculty,
      higher education institutions, community agencies and the relationships among
      these groups. An interprofessional service-learning paradigm may strengthen these
      benefits. Community settings can expose students to social and cultural
      determinants of health, in addition to those biomedical determinants more
      commonly addressed in health sciences curricula. These experiences can also
      enhance student understanding of the complexities underlying treatment and
      prevention of modern health problems, particularly chronic diseases. OBJECTIVE:
      The purpose of this initiative was to create and deliver interprofessional
      service-learning innovations that would enhance student learning and addictions
      recovery. To address this initiative, the University of Washington's Health
      Science Partnerships in Interdisciplinary Clinical Education (HSPICE) and the
      Salvation Army Adult Rehabilitation Center (ARC) began a community-campus
      partnership in 1997. Innovations took into account student educational objectives
      established by HSPICE which included: participation in interdisciplinary teams,
      in conjunction with community partners to identify and reduce population-based
      health issues, realization and articulation of biases regarding issues faced by
      the participating community, acquiring an understanding of the broader
      determinants of health and developing an understanding of why the complexity of
      population health requires interdisciplinary strategies for cost effectiveness.
      DISCUSSION: Findings are reported from evaluations, needs assessments and ongoing
      feedback of men recovering from addictions, as applied to health education
      materials and presentations developed for the ARC. Future directions are
      highlighted, including the need for further research and evaluation efforts aimed
      at rigorously assessing cost savings and student knowledge, skills and cultural
      sensitivity, among others.

PMID- 18080959
TI  - A framework for integrating interprofessional education curriculum in the health
      sciences.
AB  - CONTEXT: Traditionally, the structures of health professional education in Canada
      and elsewhere have been largely based on "silos" in which health professionals
      are educated in relative isolation to one another. The curriculum content and
      structure has followed strict disciplinary lines. Recent commissions, committees
      and policy documents in Canada have identified the importance of reshaping
      educational preparation and the professional training of health care
      professionals (Commission on the Future of Health Care in Canada, 2002; Health
      Council of Canada, 2005). OBJECTIVES: This brief communication describes an
      interprofessional curricular approach that combines characteristics of Barr et
      al.'s (2005) extracurricular and crossbar models of interprofessional education
      curriculum. METHODS: An interprofessional education curriculum that combines
      principles of an integrative, continuous, early-to-late and blended learning
      approach. DISCUSSION: The curricular approach supports exposing students to
      interprofessional education at an early stage in their training and then to
      continue with regular reinforcement. Another guiding principle is that
      interprofessional education is integrative rather than supplementary to the
      existing core curriculum. Early evaluation results suggest favourable
      satisfaction amongst students and faculty as well as significant effect on
      attitudes toward interprofessional teamwork and education. An ongoing evaluation
      is continuing based upon the various levels of Freeth et al.'s (2002)
      interprofessional education evaluation framework.

PMID- 18080960
TI  - Gender sensitization among health providers and communities through
      transformative learning tools: experiences from Karachi, Pakistan.
AB  - CONTEXT: Pakistan lags far behind most developing countries in women's health and
      gender equity. Appropriateness of health care services vis-a-vis the gender
      specific cultural norms that influence clients' needs are not very visible and
      are more difficult to monitor. Programs and services need to be sensitively
      designed to facilitate women's access to physical and social needs. This paper
      narrates the experience of working with health providers from public and private
      sectors, community, local government representatives and community-based
      organizations. Through transformative learning, this endeavour focused on
      initiating a process of sensitization on gender related health issues for women.
      APPROACH: The initiative was primarily based on the use of the following two
      standardized tools: 'Health Workers for Change' for working with health providers
      and 'Initiating Women Empowerment for Health' for interacting with the community.
      Both tools focus primarily on women's health and social issues affecting their
      health status. The research methodology used was predominantly qualitative, using
      focus group discussions, participatory rural appraisal and interactive workshops.
      IMPLICATIONS: This approach endeavours to sensitize the health service providers
      to the health needs of female clients and encourages behavioural changes.
      Simultaneously, it creates an opportunity to raise awareness among women and the
      community in general regarding appropriate health-seeking behaviour and the
      timely use of health services. The information collected is evidence for policy
      makers regarding the gender-based problems faced by women who are seeking health
      care and it suggests how to overcome these problems.

PMID- 18080961
TI  - Strengthening immunization in a West African country: Mali.
AB  - OBJECTIVES AND CONTEXT: This paper describes the preliminary outcomes of a
      collaborative capacity-building initiative performed in Mali to strengthen the
      immunization program. METHODS: We conducted baseline assessments, training and
      post-training assessments in four programmatic areas: vaccine management,
      immunization safety, surveillance, and vaccine coverage, using adapted World
      Health Organization (WHO) tools. Impact assessment was done by evaluation of
      trainee performance, programmatic impact and sustainability. RESULTS: Qualitative
      and quantitative improvement of trainee performance was seen after the training
      interventions: some knowledge improvement, greater compliance with vaccine
      management practices and improved vaccine coverage. Deficiencies in information
      transfer to the periphery were identified. CONCLUSIONS: The program involves
      shared responsibility for planning, implementation and financing with national
      stakeholders while emphasizing the training of leaders and managers to ensure
      sustainability. Although short-term gains were measured, our initial assessments
      indicate that sustained impact will require improvements in staffing, financing
      and guidelines to ensure delivery of information and skills to the periphery.

PMID- 18080962
TI  - Integrating public health and medicine: first steps in a new curriculum.
AB  - CONTEXT: Recent outbreaks of infectious diseases and humanitarian crises
      highlight the need for an understanding of public health issues in medical
      progams. However, public health teaching is perceived as peripheral in current
      Australian university medical programs. OBJECTIVE: To integrate public health
      into clinical and biomedical teaching throughout the new medicine program at the
      University of NSW. METHODS: The medicine program has been designed with three
      phases and with clinical experiences introduced early in the program. The
      approach is to trigger learning with scenarios and with vertical integration to
      reinforce lifelong learning. Public health teaching and understanding has been
      integrated into all the scenarios. DISCUSSION: As the program is only in its 4th
      year, there has been no summative evaluation of the impact of this approach.
      However, formative evaluation through Phase 1 student portfolios has demonstrated
      a good understanding of public health concepts in the satisfactory way students
      have addressed one of the eight graduate capabilities: Social and Cultural
      Aspects of Health and Disease. Another indicator of an appreciation of public
      health issues in medicine has been the choice of social and cultural topics in
      students' independent learning projects. CONCLUSION: Summative evaluation will
      occur when the University's new program graduates work in the existing health
      care system. It is proposed that they will be followed up to see whether they
      apply the public health values in their practice.

PMID- 18080963
TI  - Contextual learning to improve health care and patient safety.
AB  - CONTEXT: Two unmatched blood units were transfused to a patient undergoing
      surgery. In order to learn from this kind of error, the department had to report
      the adverse event, the staff had to discuss the situation of what went wrong and
      why and how to improve their routines to prevent such errors in the future. In
      health care, learning to improve quality and safety needs to occur at the
      individual, team and organisational levels. However, most formal learning occurs
      at the individual level at the start of a professional career. Errors are too
      often seen as personal carelessness or incompetence to be corrected by "naming,
      blaming and shaming." However, errors occur within the context of teams in
      organisations and learning needs to move from the individual to the context.
      Thus, understanding and improving how health professionals work together in
      organisations is a crucial part of the efforts to improve patient care and
      safety. OBJECTIVE: The purpose of this paper is to show how health personnel can
      improve and avoid harmful errors in patient care by delivering care within the
      setting of a clinical team and addressing and analyzing errors through a
      systematic learning process. This paper describes this learning process in detail
      and shows how it can be applied to various clinical situations to improve patient
      safety. FINDINGS: Learning takes place on several levels: from single-loop
      learning (adaptive learning) through double-loop learning (reflection in and on
      action) to triple-loop learning (meta-learning), and extending ones understanding
      and competencies of how to learn individually and in groups. Linking professional
      knowledge (e.g. medical sciences) and improvement knowledge (knowledge of system
      improvement), and paying attention to multidisciplinary team learning, are
      crucial to understanding how patient care and safety can be improved in clinical
      microsystems.

PMID- 18080964
TI  - Clinical skills training in a skills lab compared with skills training in
      internships: comparison of skills development curricula.
AB  - CONTEXT: The necessity of learning skills through "integrated skills training" at
      an undergraduate level has been supported by several studies. The University of
      Antwerp implemented undergraduate skills training in its renewed curriculum in
      1998, after it was demonstrated that Flemish students did not master their
      medical skills as well as Dutch students who received "integrated skills
      training" as part of their undergraduate medical course. AIM: The aim of this
      study was to compare the skill outcome levels of two different student
      populations: students who had been trained in basic clinical skills mainly
      through clinical internships in year 7 with students who had learned these skills
      through an integrated longitudinal programme in a special learning environment in
      years 1-5 prior to their internship experience. STUDY SAMPLE: Students of the
      traditional curriculum learned skills through a 75 hour programme in years 4 and
      5, through plenary sessions followed by a 12 month period of internships during
      which skills could be further practiced. We tested this group right after
      completion of their internships. Students from the renewed curriculum followed a
      200 hour intensive small group skills training programme offered in years 1-5.
      This group was tested before starting their internships. RESULTS: On global OSCE
      scores, renewed curriculum students had significantly higher overall scores
      (p<0.001) and they scored significantly higher at 6 of 15 stations. There was no
      significant difference at 8 stations, while traditional curriculum students
      scored better at station 1. DISCUSSION: 5 years and 200 hours of integrated
      undergraduate skills training is more effective as a method of learning basic
      clinical skills, compared to learning these skills through 75 hours of
      traditional skill training and reinforcement of these skills in 12 month clinical
      internships, when measured by means of an OSCE.

PMID- 18080965
TI  - Introduction of regular formative assessment to enhance learning for clinical
      students at Muhimbili University College, Tanzania.
AB  - OBJECTIVE: To determine if undertaking regular Formative Assessment (FA) in the
      setting of our medical school enhanced the students' learning experience.
      METHODS: An FA intervention was designed and implemented with clinical students
      during their clerkship in the academic year 2003/04. FA was administered as
      structured verbal comments on daily clinical case presentations. Evaluation of
      the intervention included pre- and post-surveys exploring the perceptions of
      students and teachers on the quality of the learning experience. Focus group
      discussions with students and with teachers were held at the start and conclusion
      of the intervention to identify strengths and weaknesses of FA. FINDINGS: All
      participating teachers perceived that students were interested in learning before
      the intervention. Teachers who perceived that students achieved the set learning
      objectives increased from 0% before to 28% after the intervention. Most teachers
      (71%) and students (86%) perceived FA to enrich students' learning experience.
      Students appreciated the positive change in teachers' attitudes during the FA
      intervention. Both students and teachers recommended that FA become a regular and
      routine activity. CONCLUSIONS: Students and teachers viewed FA as a positive,
      feasible intervention. They thought it enriched the learning process and
      recommended it be a routine learning activity.

PMID- 18080966
TI  - Report on an interdisciplinary program for allied health.
AB  - CONTEXT: A central recommendation from the Pew Health Commission to educators has
      been to empower future care providers to function effectively as teams.
      Administrators and faculty members within a school of allied health sciences thus
      established an interdisciplinary program where students would learn to function
      as team members and demonstrate competencies required for practice in diverse,
      demanding, and continually changing health care environments. Students from five
      disciplines have participated in featured events, mentored activities and
      capstone projects, earning credit in an interdisciplinary course of study that
      complements offerings in their home disciplines. GOAL: This follow-up article
      reports on the progress and development since 2002 of an interdisciplinary
      program known as Team IDEAL. Formative evaluation measures used to assess
      satisfaction with the program are presented alongside a discussion of new
      directions. CONCLUSION: Team IDEAL will move forward in a streamlined form that
      reflects its central aim. IDEAL leadership will remain cognizant of the effects
      of discipline-specific curricular changes, complex programming, and student
      perspectives on the process interdisciplinary education.

PMID- 18080967
TI  - Global poverty, human development, and the brain drain.

PMID- 18080969
TI  - Vietnamese women immigrants' life adaptation, social support, and depression.
AB  - The purpose of this study was to explore the relationships between life
      adaptation, social support, and depression among migrant Vietnamese women living
      in Meinong Township, Kaohsiung County. With a cross-sectional study design, 143
      participants were recruited by purposive sampling. Structured questionnaires
      including Demographic Inventory Scale, Life Adaptation Scale, Social Support
      Scale, and Beck Depression Inventory Scale were used. Data were analyzed with
      Pearson's correlation and One-way ANOVA. The results showed that Vietnamese
      women's social support was significantly correlated with the length of time
      living in Taiwan, the length of marriage, and their husbands' age. Women's social
      support was significantly different with languages in common, the way of
      acquaintance with her husband, and family members living together. Depression was
      significantly different with family income. Life adaptation was also
      significantly different with family income. Moreover, there was a significantly
      positive correlation between Vietnamese women's social support and life
      adaptation, and significantly negative correlations between Vietnamese women's
      social support and depression, and between their life adaptation and depression.
      The study findings could be used as references for health professionals and
      government agencies to institute strategies and policies for promoting migrant
      Vietnamese women's life adaptation.

PMID- 18080970
TI  - Research into care quality criteria for long-term care institutions.
AB  - The purpose of this paper was to determine the criteria that reflect the quality
      of care provided by long-term care institutions. Research was conducted using a
      two-step procedure that first utilized the SERVQUAL model with Fuzzy Delphi
      Method to establish the proper criteria by which service quality could be
      measured. A total of 200 questionnaires were mailed to expert respondents, of
      which 89 were returned and 77 deemed valid for use in this study. We then applied
      the Multi-Criteria Decision Making Process to determine the degree of importance
      of each criterion to long-term care institution service quality planning work.
      Secondly, 200 questionnaires were distributed and 74 valid responses were
      returned. Based on the 5 SERVQUAL model constructs, this study found 17 of the 28
      criteria, to be pertinent to nursing care quality, with those in the
      Responsiveness and Empathy domains being the ones most critical.

PMID- 18080971
TI  - Effects of internal marketing on nurse job satisfaction and organizational
      commitment: example of medical centers in Southern Taiwan.
AB  - As nurses typically represent the largest percentage of employees at medical
      centers, their role in medical care is exceptionally important and becoming more
      so over time. The quality and functions of nurses impact greatly on medical care
      quality. The concept of internal marketing, with origins in the field of market
      research, argues that enterprises should value and respect their employees by
      treating them as internal customers. Such a marketing concept challenges
      traditional marketing methods, which focus on serving external customers only.
      The main objective of internal marketing is to help internal customers
      (employees) gain greater job satisfaction, which should promote job performance
      and facilitate the organization accomplishing its ultimate business objectives. A
      question in the medical service industry is whether internal marketing can
      similarly increase the job satisfaction of nurses and enhance their commitment to
      the organization. This study aimed to explore the relational model of nurse
      perceptions related to internal marketing, job satisfaction, and organizational
      commitment by choosing nurses from two medical centers in Southern Taiwan as
      research subjects. Of 450 questionnaire distributed, 300 valid questionnaires
      were returned, giving a response rate of 66.7%. After conducting statistical
      analysis and estimation using structural equation modeling, findings included:
      (1) job satisfaction has positive effects on organizational commitment; (2) nurse
      perceptions of internal marketing have positive effects on job satisfaction; and
      (3) nurse perceptions of internal marketing have positive effects on
      organizational commitment.

PMID- 18080972
TI  - Gender differences in quality of life for post coronary artery bypass grafting
      patients in Taiwan.
AB  - The purpose of this study was to investigate gender differences in quality of
      life for post Coronary Artery Bypass Grafting (CABG) patients in Taiwan. Cross
      sectional survey research design and purposive sampling were used in this study,
      for which 100 subjects, including 50 males and 50 females, were recruited from a
      medical center in northern Taiwan. Quality of life was measured by Short Form 36,
      while gender role function and demographic data were collected using a
      demographic questionnaire. An Independent t test and one way ANOVA were employed
      to analyze data. Study results showed significant differences in quality of life
      between genders. There was a statistically significant difference in the physical
      component summary score, post-CABG, between males (M=45.5) and females (M=40.1,
      p< .05), which indicates that men demonstrated higher physical functioning than
      women. Within this component, the greatest difference between the genders was
      noted in sub-items related to physical functions. Men and women achieved mean
      scores of 42.2 and 37.9, respectively (p< .05). For the mental component summary
      section, sub-items related to vitality also demonstrated statistical
      significance; with men achieving a mean score of 49.6 and women a mean score of
      45.2 (p< .05). Of interest, post-CABG patients who had greater role
      responsibilities, such as taking care of elderly or doing housework, obtained
      significantly higher quality of life scores.

PMID- 18080973
TI  - Suk-Sam-Bai: the quality of life perceptions among middle-aged women living with
      a disability in Isaan, Thailand.
AB  - Midlife represents a time of shifting roles and biopsychosociocultural change for
      women. Physical disabilities compound the effect of such on daily life and
      quality of life. The objective of this study was to explore how middle-aged women
      with disabilities in Isaan perceived their current quality of life. A qualitative
      method was applied. Data were collected using in-depth interviews and
      observations. Sixteen disabled women were recruited through purposive and
      theoretical sampling. Qualitative data were analyzed using both thematic and
      content analysis. Triangulation was used to ensure data rigor. "Suk-Sam-Bai" was
      a term frequently used by disabled women in this study to define their quality of
      life. Life experiences, goals, and achievements lead to experiences of gain,
      maintenance, and loss in three interrelated aspects that include: fluctuations in
      physical capacity and health, maintaining gender role, and a caring and
      supportive environment. These three aspects impact on an individual's personal
      perception of Suk-Sam-Bai. Study findings indicate that gender and culture play
      significant roles in the lives of disabled women in Isaan culture. Based on study
      findings, providing gender- cultural sensitive nursing care is essential to
      delivering comprehensive and effective healthcare to women with disabilities.

PMID- 18080974
TI  - The effectiveness of hospital-based diabetes case management: an example from a
      northern Taiwan regional hospital.
AB  - The aim of this study was to design, implement and evaluate disease outcomes at a
      regional hospital- based case management program of care for patients with type 2
      diabetes. A medical team and practice guidelines were established in line with
      the health insurance strategy of Taiwan's Bureau of National Health Insurance
      (BNHI) and American Diabetes Association (ADA) Standards of Care for Diabetes
      (2003 edition). Also, a set of self-care booklets was designed suitable for use
      by the subject group. The study was prospective and followed the patients from
      enrollment to one year. Patient outcomes were determined based on laboratory
      examinations and recorded self-care behavior. Data were collected at enrollment
      and over 4 follow-up times within a one year period. Generalized Estimating
      Equation (GEE) multiple linear regression and logistic regression were used for
      repeated measurements and adjustments of the effects of specific prognostic
      factors. Sixty subjects diagnosed with type 2 diabetes (mean duration 3.25 years)
      were recruited. All participants were married with a mean age of 52.5 years. A
      majority (58.3%) was male and 65% were ethnic Hakka. Self-care knowledge and
      behavior accomplishment rates were: taking medications by oneself, 91.3% (knowing
      medicines, 25.4%); hypoglycemia management, 23.3%; monitoring blood sugar, 46.7%;
      exercise, 35.8%; diet management, 51.7% and foot care, 92.8%. Significantly
      improved ADA diabetes care standard items included HbA1C (p< .0001), fasting
      glucose (p< .01) and triglycerides (p< .05). The study incorporated evidence
      based guidelines, public health insurance strategies and self-care booklets into
      a protocol to provide comprehensive care. The implemented diabetes program
      achieved diabetes care goals and improved patient self-care.

PMID- 18080975
TI  - An investigation into competence in TCM of BSN graduates from technological
      universities in Taiwan.
AB  - The purpose of this study was to determine what competences in Traditional
      Chinese Medicine (TCM) should be possessed by Bachelor of Science in Nursing
      (BSN) graduates from technological universities in Taiwan. There were two phases
      in this study: focus groups and expert panel discussion. First, we held four
      focus groups, and interviewed 31 participants, including consumers, nursing staff
      and clinical nursing faculty. The interview tapes were transcribed verbatim, were
      proofed for accuracy and the content was analyzed. The results were then
      discussed by four academic experts in a panel discussion. Results indicated that
      the TCM competences of BSN graduates from technological universities should
      include the following: (1) to understand the basic concepts of TCM, including
      Yin/Yang, the Five Evolutive Phases, holistic view, the Five Viscera and Six
      Bowels, Meridians, etiology, and concepts of therapy and health preservation; (2)
      to recognize the cold and hot nature of food; (3) to illustrate the common
      dietetic care for immune enhancement in the four seasons, and the foods that help
      postnatal and postoperative physical regeneration; (4) to illustrate the
      properties, indications, and administration of common Chinese medicines,
      including: Ginseng, Lycium, Astragalus, Angelica sinensis (danggui),
      Chrysanthemum, Pinellia, Zizyphi fructus; (5) to describe the properties,
      indications, adverse effects, and administration of Siwutang and Shenghuatang;
      (6) to describe basic principles of administering both Chinese medicine and
      Western medicine; (7) to describe the indications and cautions of the following
      techniques: acupuncture, scraping therapy, and cupping; (8) to implement
      acupressure as a measure for promoting comfort under the following conditions:
      pain, vomiting, insomnia, palpitations; and (9) to demonstrate an open mind and
      cautious attitude to respect consumers using TCM. Results of the study can serve
      as a reference for nurse educators when training BSN graduates from technological
      universities in TCM competences.

PMID- 18080976
TI  - Quality of life, symptom distress, and social support among renal transplant
      recipients in Southern Taiwan: a correlational study.
AB  - Quality of life is an important indicator for evaluating therapeutic outcomes and
      mortality in patients with end-stage renal disease. Few studies have explored the
      impact of symptom distress and social support on quality of life in this
      population. A correlational study was designed to examine the influence of
      symptom distress, social support and demographic characteristics on quality of
      life in renal transplant recipients. A convenience sample of 113 renal transplant
      recipients was recruited from a medical center in Southern Taiwan. A structured
      questionnaire was used to collect data. This four-part tool included: Quality of
      Life Index--Kidney Transplant Version III, Physical Symptom Distress Scale,
      Social Support Scale, and demographic characteristics. Data were analyzed by
      descriptive and inferential statistics (SPSS 10.1 statistical package).
      Percentage, rank, mean and standard deviation, t-tests, chi-square, ANOVA,
      Pearson's correlation and multiple regression were computed. Results showed that
      renal transplant recipients had a moderate quality of life. Social support and
      symptom distress, age, employment status, and household income significantly
      explained 28.8% of the variance in quality of life. Findings suggest implications
      for interventional programming and research aimed toward improving quality of
      life, including individual and family-based approaches designed to enhance
      recipients' social support and address effective management of symptoms.
      Recruiting a transplant clinical nurse specialist to design and implement an
      intervention program also is recommended.

PMID- 18080977
TI  - [Palliative care in patients with advanced chronic obstructive pulmonary
      disease].

PMID- 18080978
TI  - [Domiciliary oxygen therapy].

PMID- 18080979
TI  - [Cytokeratins - tissue and biochemical markers of non-small cell lung cancer].

PMID- 18080980
TI  - [The prognostic value of cytokeratin 19 expression in non-small cell lung
      cancer].
AB  - INTRODUCTION: Cytokeratins are important part of cytoskeleton. Cytokeratin 19 (CK
      19) belongs to type I cytokeratins. Lung cancer is currently most frequently
      diagnosed neoplasm in males in many developed countries and in Poland. The
      prognosis in lung cancer remains unfavourable. The aim of this study was to
      evaluate the prognostic value of cytokeratin 19 expression in non-small cell lung
      cancer. MATERIAL AND METHODS: We examined the degree of cytokeratin 19 expression
      in 94 patients with non-small cell lung cancer, who had undergone surgery. The
      group consisted of 64 men and 30 women. The mean age was 59,12 +/- 8,61 years.
      Histological diagnosis was squamous cell carcinoma in 59 patients, adenocarcinoma
      in 26 patients, large cell carcinoma in 5 patients and non-small cell lung cancer
      without determination of the subtype in 4 patients. Cytokeratin 19 expression was
      examined immunohistochemically with Monoclonal Mouse Anti-Human Cytokeratin 19
      Clone BA 17 DAKO M 0772. All patients were observed for 24 months. 45 patients
      (48%) survived, 49 died. RESULTS: In all examined tumors we observed positive
      cytoplasmatic staining of cytokeratin 19. In 41 cases (44%) it was weak staining
      (CK 1), in 35 (37%) medium (CK 2) and in 18 (19%) strong one (CK 3). We
      demonstrated higher expression of cytokeratin 19 in these patients, who survived
      2 years (p = 0,003). We also observed relationship between higher expression of
      CK 19 and survival in patients with squamous cell cancer, but there was no
      correlation with survival in patients with adenocarcinoma. CONCLUSIONS: Our
      results suggest that the degree of cytokeratin 19 expression could be a new
      prognostic factor in non-small cell lung cancer. Cytokeratin 19 expression has
      prognostic value in patients with squamous cell lung cancer but not in patients
      with adenocarcinoma.

PMID- 18080981
TI  - [The variability of peak inspiratory flow (PIF) on valves imitating dry powder
      inhalers resistance during asthma and COPD exacerbations].
AB  - INTRODUCTION: Drugs used in asthma or COPD exacerbation are delivered to the
      lungs by inhalation. This is facilitated, among other factors, by the use of dry
      powder inhalers (DPIs). Lung deposition from DPI depends predominantly on peak
      inspiratory flow (PIF). The aim of the study was to asses the variability of PIF
      generated by patients using different types of DPI inhalers during asthma or COPD
      exacerbation and to trace possible relationships between PIF value and some
      spirometric values. MATERIAL AND METHODS: There were 28 patient fulfilling
      inclusion criteria, among them 17 (4 women) were suffering from COPD and 11 (8
      women) from asthma. Spirometry, PEF and PIF measurements were performed in the
      first and the last day of hospitalisation. Peek inspiratory flow was obtained
      using In-Check DIAL - a device which simulated airflow resistances equivalent to
      Turbuhaler, Diskus and Aeroliser respectively. RESULTS: The significant
      improvement in PIF was observed only in patients with COPD. There were no
      statistically significant correlations between PIF and both FEV1 and PEF except
      those in the first day of hospitalization in COPD patients (r = 0.66-0.81).
      Optimal PIF was achieved in all patients only with Diskus. CONCLUSIONS:
      Measurements of peek inspiratory flow are useful in choosing the most suitable
      DPI for patients with COPD and asthma exacerbations. We conclude that in those
      patients, PIF measurement should complement a standard spirometry.

PMID- 18080982
TI  - [Long-term domiciliary oxygen therapy (LTOT) in Poland in the years 1986-2005].
AB  - INTRODUCTION: Long-term domiciliary oxygen therapy (LTOT) is part to of pulmonary
      care system. Uniform qualification criteria and methods of follow-up for patients
      undergoing LTOT have been adopted. There are 63 LTOT centres located in Poland
      run by specialists in pulmonology. On the occasion of 20 years of LTOT in Poland,
      an analysis of its development, number of patients treated, diagnoses, survival
      and equipment was performed. MATERIAL AND METHODS: Data were taken from
      structurized LTOT centres reports. RESULTS AND CONCLUSIONS: A history of LTOT may
      be divided into 3 periods, steady grow in the years 1986-1991, stagnation between
      1992-2000 and rapid grow in the last 3 years. On 01.01.2006 there was 2601
      patients receiving LTOT therapy. The most common diagnosis was COPD (85%)
      followed by kyphoscolisis (5%), TB sequels (4.6%), IPF (3.6%) and other rare
      diseases. Treatment is reimbursed by the National Health System. Oxygen is
      administered via an oxygen concentrator. Due to insufficient resources from the
      NHS the needs for LTOT treatment are not fulfilled. There are 8.4 patients
      treated with LTOT per 100 000 people, with large regional differences ranging
      from 3.7 to 14.9/100 000. The most frequent cause of death in patients receiving
      LTOT treatment was exacerbation of respiratory failure (71.3%), followed by
      sudden death (5.1%), myocardial infarction or pulmonary embolism (4.4%), lung
      cancer (4%) and other or not known causes (15.2%). Survival in patients receiving
      LTOT treatment from the years 1986-1995 was rather short: 54.6% survived less
      than 3 years, 3-4 years survived 13.3%, 4-5 years 11.3% and more than 5 years
      survived 19.7% of treated patients.

PMID- 18080983
TI  - [Chemotherapy of advanced non small cell lung cancer: effect on survival and
      symptoms affecting quality of life].
AB  - INTRODUCTION: The study presents treatment results of 168 patients with non small
      cell lung cancer in stage IIIB and IV treated since year 2002 to 2006 in
      Oncological Center in Cracow. MATERIAL AND METHODS: Four regimens of
      chemotherapy: EP (cisplatin, vepesid), MVP (mitomycin C, vinblastin, cisplatin),
      PN (cisplatin,vinorelbin) and PG (cisplatin, gemcytabin) were used. RESULTS:
      Average survival time in group treated with MVP regimen was 7,8 months (median
      4,3 months), PG 7,1 months (median 7,3 months), EP 10,2 months (median 7,5
      months), PN 14,1 months (median 9,8 months). Differences in median survival time
      were not significant. Average time to progression in group treated with MVP
      regimen was 3,5 months (median 2,6 months), PG 5,2 months (median 5,8 months): EP
      6,6 months (median 5,2 months), PN 6,7 months (median 5,6 months). Improvement in
      control of symptoms regarding dyspnea, pain and cough was reached in 60%, 38,7%
      and 60% of patients respectively. There were no significant differences between
      chemotherapy regimens regarding improvement in symptoms control. CONCLUSIONS:
      Cisplatin + vinorelbin regimen can be recommended as standard method because of
      the best treatment results.

PMID- 18080984
TI  - [Analysis of memory dysfunction in OSAS patients].
AB  - INTRODUCTION: Hypoxia, reduced cerebral perfusion and sleep fragmentation as the
      result of recurrent apnea-related episodes in sleep apnea patients may have
      impact on mental performance such as memory and concentration. Increased number
      of traffic accidents has been observed in OSAS patients. Patients often complain
      of concentration and memory problems, as well as sleepiness. The diagnosis of
      perception processes requires neuropsychological diagnosis. MATERIAL AND METHODS:
      22 sleep apnea patients were involved in the study. RESULTS: Correlation between
      the number of mistakes in Benton Test and AHI has been observed (r = 0.63; p <
      0.005), as well as between AHI and memory in Number Repeating Test based on
      Wechsler-R (r = 0.49; p < 0.05). No correlations have been found between results
      of Benton Test and sleepiness scale. Mean saturation and lowest saturation didn't
      show any correlation with neuropsychological tests. Qualitative analysis of
      mistakes in both Benton and Bender-Gestalt Tests did not suggest any organic
      changes in the brain. AHI seems to be more important predictor of memory
      dysfunction than sleepiness scale score. CONCLUSIONS: Specific tests, specially
      used in neuropsychological diagnosis, could be useful in the diagnosis of memory
      perception disorders and treatment effectiveness assessment in OSAS patients.

PMID- 18080985
TI  - [Evaluation of humoral immune response against mycobacterial antigens in
      bronchoalveolar lavage fluid from patients with pulmonary tuberculosis confirmed
      by genetic and culture methods].
AB  - INTRODUCTION: The resistance to TB is cells-mediated but humoral response is
      common and may be correlated with the lack of effective local cellular defence
      mechanisms. The goal of the study was to evaluate IgG, IgA and IgM mediated
      humoral immune response against 38kDa plus 16kDa and 38kDa plus lipoarabinomannan
      (LAM) mycobacterial antigens in BALF from patients with culture confirmed and PCR
      positive pulmonary tuberculosis (TB) compared to non-tuberculous controls (NTB).
      MATERIAL AND METHODS: 79 BALF samples (46 TB and 30 NTB) were examined. In 25
      BALF samples from TB patients nucleic acids from M. tuberculosis were detected by
      PCR method. Commercially available ELISA - based assays against proteins 38kDa
      and 16kDa or 38kDa plus LAM were used. Three different dilutions of BALF: 1 : 1
      and 1 : 10 were tested. Mean IgG level against 38 + LAM was significantly higher
      in TB group compared to control (p < 0,0001). No difference was observed between
      TB and NTB group in titer of IgM antibodies. RESULTS: Sensitivity of the tests
      based on IgG anti38kDa + 16kDa was 49%, IgG anti38kDa + LAM - 33%, IgA anti38kDa
      + LAM - 100%, IgM anti38kDa + LAM - 35%. Specificity of examined assays: IgA
      anti38kDa + LAM - 13%, IgM anti38kDa + LAM - 75%, IgG anti38kDa + 16kDa - 87%,
      IgG anti38kDa + LAM - 93%. The findings of the study indicate that TB is
      associated with the presence of detectable levels of antibodies in the BALF.
      CONCLUSIONS: Examined tests detecting IgG in BALF can be used in combination with
      other diagnostic methods to increase diagnostic accuracy of pulmonary TB.

PMID- 18080986
TI  - [The relationship between markers of airway inflammation and thickness of the
      basement membrane in patients with asthma].
AB  - INTRODUCTION: Airway inflammation and remodeling are well recognized features of
      asthma. Remodeling is usually regarded as a consequence of chronic inflammation,
      however there are also data suggesting that remodeling is a relatively
      independent process in asthma. Neither inflammation nor remodeling is a uniform
      process. Thus the precise relationship between markers of inflammation and
      different patterns of remodeling are still matter of investigations. The aim of
      the study was to assess the relationship between total and differential cell
      count in induced sputum (IS) and BALF, and thickness of the basement membrane
      (BM) in patients with stable asthma. MATERIAL AND METHODS: 18 patients with
      asthma (M/F 9/9, mean age 36 +/- 15 yrs). Duration of symptoms amounted to 12.7
      +/- 11.5 years. Patients who have not been treated with steroids for at least 3
      months were enrolled to the study. All patients underwent sputum induction and
      fiberoptic bronchoscopy with BAL and bronchial biopsies. Total and differential
      cell counts were measured in induced sputum and BALF. Light-microscopic
      measurements of BM thickness were performed in hematoxylin-eosin stained slides
      of bronchial wall specimens with semi-automatic software analysis. RESULTS: Mean
      BM thickness was 12.9 +/- 2.8 microm (range: 8.5-20.7 microm). Total sputum cell
      count was 3.4 +/- 2.7 x 106 cells/ml, whereas in BALF 9.7 +/- 10.2 x 106
      cells/ml. There was no correlation between differential cell count in induced
      sputum and BALF. No significant correlations between BM thickness and total and
      differential cell count in IS and BALF were observed. There also was no
      correlation between BM thickness and length of asthma duration or degree of the
      disease. CONCLUSIONS: There was no relationship between BM thickness and total
      number of cells nor number of eosinophils in BALF and/or IS.

PMID- 18080987
TI  - [Complex sleep apnea syndrome].
AB  - Some patients with obstructive sleep apnea (OSA) develop persistent central sleep
      apnea activity when started on continuous positive airway pressure (CPAP). This
      recently recognized syndrome, complex sleep apnea syndrome (CompSAS), is thought
      to be due to dysfunction of the respiratory center in a setting of an obstructive
      sleep apnea. We present the current knowledge on epidemiology, pathophysiology,
      and treatment options in CompSAS. We review the current literature on CompSAS,
      and present our own data on this interesting condition.

PMID- 18080988
TI  - [Histone dependent signalization during pharmacotherapy of chronic obstructive
      pulmonary disease].
AB  - Chronic obstructive pulmonary disease (COPD) is a 4(th) major cause of morbidity
      and mortality worldwide. Cigarette smoking and oxidative/nitrosative stress
      leading to chronic inflammation is considered as a major cause of COPD but up to
      now, details of molecular pathways responsible for development of disease are
      unknown. Recent reports indicate the role of disruption in histone function in
      promoting synthesis of inflammatory cytokines through increased gene
      transcription which underlies disease development. Core histone
      acetylation/deacetylation regulate their transcription activity and drug induced
      changes of its intensity may be an interesting field of further research. In this
      article the opinions about the role of steroids as inhibitors of the inflammatory
      process as well as resistance to steroids have been presented. Findings from
      studies which aimed to explore the anti-inflammatory activity of drugs such as
      theophylline and N-acetylcysteine and their ability to suppress oxidative stress
      may suggest the usefulness of these drugs in causative treatment of COPD.
      However, further studies are necessary to confirm these findings.

PMID- 18080989
TI  - [Palliative care in chronic obstructive pulmonary disease].
AB  - Traditionally focusing on terminally ill cancer patients, palliative care
      services have recently attempted to involve patients with other chronic, life -
      threatening diseases, e.g. chronic obstructive pulmonary disease (COPD). In this
      group of patients both quality of life and life expectancy is poor.
      Unfortunately, patients with COPD don't receive adequate special medical service,
      although this progressive disease causes almost as many deaths as lung cancer.
      The suffering of patients dying from COPD is not smaller than cancer patients.
      The major symptoms are usually dyspnoe, cough, fatigue, depression, emotional and
      psychosocial problems. In fact, their needs are really palliative, so we try to
      pay attention to the quality of life of people suffering from COPD. It is
      important to underline that medical palliation of these patients falls not only
      to the management of the main clinical symptoms, but also to adopt a holistic,
      multiprofessional approach and working with their families and caregivers.

PMID- 18080990
TI  - [Pathogenesis and clinical features of nonasthmatic eosinophilic bronchitis].
AB  - The introduction of induced sputum, as the diagnostic and research tool allowed
      to define nonasthmatic eosinophilic bronchitis characterized as a chronic cough
      in patients with no symptoms or objective evidence of variable airflow
      obstruction, with normal airway hyperresponsiveness and sputum eosinophilia.
      Eosinophilic bronchitis is an important cause of chronic cough. Studies in which
      the assessment of airway inflammation has been undertaken in chronic cough
      patients have shown that nonasthmatic eosinophilic bronchitis accounts for 10 to
      30% of cases referred for specialist investigation. Eosinophilic bronchitis, like
      asthma, is characterized by eosinophilic airway inflammation, but unlike asthma,
      there is no airway hyperresponsiveness or bronchoconstriction. The airway
      immunopathology of asthma and eosinophilic bronchitis are almost identical. An
      obvious question is why an apparently similar pattern of airway inflammation is
      associated with different functional abnormalities in patients with nonasthmatic
      eosinophilic bronchitis and asthma. The differences in functional association may
      be related to differences in the localization of mast cells within the airway
      wall, with airway smooth muscle infiltration occurring in patients with asthma,
      and epithelial infiltration in patients with nonasthmatic eosinophilic
      bronchitis.

PMID- 18080991
TI  - Organising pneumonia and lung cancer - case report and review of the literature.
AB  - Organising pneumonia (OP) is a distinct clinicopathological entity resulting from
      pulmonary reaction to noxious environmental or endogenous factors, but also
      idiopathic cases have been noted. Frequently, small foci of OP accompany lung
      cancer infiltrations. Also OP is sometimes a reaction to radio- or chemotherapy,
      but it is rarely a predominant lesion in the course of lung cancer. We present
      the case of 65-year-old patient who presented with fever, dry cough, exertional
      dyspnoea and pneumonic consolidation in the right lower lobe. Bronchoscopy
      revealed squamous carcinoma obstructing the right lower bronchi. He was
      surgically treated, and the right lower lobe was resected. Pathological
      examination of a specimen revealed only small infiltration of carcinoma cells in
      the wall of the bronchi and large confluent areas of organising pneumonia.
      Surgery was a sufficient treatment for both diseases. Six months later he was in
      good condition without any pulmonary infiltrations. To sum up, a case of
      endobronchial squamous cell carcinoma in stage T1N0M0 with predominant clinical
      and radiological signs of OP is presented.

PMID- 18080992
TI  - [Pulmonary malakoplakia and Rhodococcus equi infection. A report of two cases and
      review].
AB  - Malakoplakia is a rare, chronic, granulomatous disease seen in immunocompromised
      patients, caused by multiple infectious agents, most often bacteria.
      Microscopically, accumulations of macrophages with granular cytoplasm and intra-
      or extracellular structures, called Michaelis-Gutmann bodies are characteristic.
      Main cause of pulmonary malakoplakia is Rhodococcus equi infection. We report two
      cases of pulmonary malakoplakia, in one case R. equi infection was confirmed. We
      also present a summary of recent knowledge about the pathogenesis, morphology and
      clinical course of the disease.

PMID- 18080994
TI  - Homology versus analogy: possible evolutionary relationship of immunoglobulins,
      cupredoxins, and Cu,Zn-superoxide dismutase.
AB  - The 'immunoglobulin-like' fold is one of most common structural motifs observed
      in proteins. This topology is found in more than 80 superfamilies of proteins,
      including Cu,Zn-superoxide dismutase (SOD) and cupredoxin. Evolutionary
      relationships have not been identified, but may exist. The challenge remains,
      therefore, of resolving the issue of whether the diverse distribution of the fold
      is accounted for by divergent evolution of function or convergent evolution of
      structure following multiple independent origins of function. Since the early
      studies that revealed conformational similarity of immunoglobulins and other
      proteins, the number of primary structures available for comparison has
      dramatically increased and new computational approaches for analysis of sequences
      have been developed. It now appears that a hypothesis of a common evolutionary
      origin for cupredoxins, Cu,Zn-SOD, and immunoglobulins may be credible. The
      distinction between protein homology and protein analogy is fundamental. The
      immunoglobulin-like fold may represent a robust system within which to examine
      again the issue of protein homology versus analogy.

PMID- 18080996
TI  - On molecular recognition of an uranyl chelate by monoclonal antibodies.
AB  - The energy landscape of the uranyl (UO2) chelate dissociated from a monoclonal
      antibody U08S was investigated using dynamic force spectroscopy (DFS). The uranyl
      ion (UO2(2+)) is chelated with the ligand dicarboxy-phenanthroline (DCP). The
      monoclonal antibody U08S was raised against UO2-DCP and does not cross-react with
      DCP alone. The results of plotting the most probable force against the logarithm
      of the loading rate show two distinguished values of slopes of multiple fitting
      lines, as observed in our previous study on that system with monoclonal antibody
      U04S (Odorico et al., 2007a. Biophys. J. 93: 645-654.). It indicates an unbinding
      process undergoing at least two activation states. We have generated the
      histogram of unbinding events with respect to the composite stiffness of the
      complex between the protein and the uranyl compound. Combining the model of Bell
      and Evans with that of Williams, we have estimated the number of parallel bonds
      involved in the unbinding process and determined the value of stiffness for
      individual bonds. We propose that the uranyl compound binds to the two antibodies
      U04S and U0c at structurally equivalent locations and forms the interaction with
      similar coordination modes. In addition, the unbinding process goes through two
      steps; the first weakens the bonding of the central metal with AspL50 of the
      antibody and the second breaks other non-bonded interactions of the compound with
      the antibody.

PMID- 18080995
TI  - Past, present and future of atomic force microscopy in life sciences and
      medicine.
AB  - To introduce this special issue of the Journal of Molecular Recognition dedicated
      to the applications of atomic force microscopy (AFM) in life sciences, this paper
      presents a short summary of the history of AFM in biology. Based on contributions
      from the first international conference of AFM in biological sciences and
      medicine (AFM BioMed Barcelona, 19-21 April 2007), we present and discuss recent
      progress made using AFM for studying cells and cellular interactions, probing
      single molecules, imaging biosurfaces at high resolution and investigating model
      membranes and their interactions. Future prospects in these different fields are
      also highlighted.

PMID- 18080997
TI  - Atomic force microscopy in life sciences and medicine. Editorial.

PMID- 18080998
TI  - Progression of cortical and spinal dysfunctions over time in amyotrophic lateral
      sclerosis.
AB  - In view of the conflicting results about the links between lower and upper motor
      neuron (LMN, UMN) dysfunction in amyotrophic lateral sclerosis (ALS), we
      undertook this study to correlate their changes over time. Single motor units
      (MUs) were characterized by their macro-MU potentials, twitch amplitude, and
      excitatory responses to transcranial magnetic stimulation (TMS). Ten ALS patients
      were studied 2 to 4 times and their data were subdivided into epochs
      corresponding to mean disease duration of 12 (58 MUs), 20 (60 MUs), 32 (50 MUs),
      43 (40 MUs), and 168 months (55 MUs). The MU size increased and the contractile
      effectiveness and the excitatory response rates decreased significantly with
      time. The contractile effectiveness of MUs producing normal excitatory responses
      decreased with time, whereas a gradual loss of excitatory responses was observed
      among MUs with normal electromechanical properties. Since no correlation was
      found between UMN and LMN dysfunction, we conclude that UMN and LMN probably
      degenerate independently in ALS.

PMID- 18080999
TI  - Isolated fetal ascites due to Budd-Chiari syndrome.

PMID- 18081000
TI  - The cannabinoid receptor agonist nabilone for the treatment of dementia-related
      agitation.

PMID- 18081001
TI  - Firearms and dementia: a smoking gun?

PMID- 18081002
TI  - Association of catechol-O-methyltransferase variants with loudness dependence of
      auditory evoked potentials.
AB  - OBJECTIVE: The loudness dependence of auditory evoked potentials (LDAEP) provides
      a measure of the central serotonergic activity. As dopamine transporter
      availabilities also correlate with LDAEP, a dopaminergic influence is probable.
      The enzyme catechol-O-methyltransferase (COMT) is involved in the inactivation of
      synaptic dopamine. The aim of this study was to investigate the relationship
      between genetic variants of the COMT gene influencing synaptic dopamine levels
      and the LDAEP. METHODS: Rs737865 in intron 1, rs4680 coding for a Val158Met
      substitution and rs165599 in the 3' region were investigated in 95 carefully
      selected healthy subjects of German descent (41 males, 54 females). The LDAEP was
      calculated as a linear regression slope with stimulus intensity as independent
      and N1/P2-amplitude as dependent variables. RESULTS: Single marker analysis
      showed weak associations for two single nucleotide polymorphisms (SNPs)
      (rs737865: CC vs. T allele carrier; rs4680: G-allele carrier vs. AA homozygotes).
      A-G (rs4680-rs165599) was associated with lower LDAEP scores. Accordingly,
      haplotype analysis with all SNPs (rs737865-rs4680-rs165599) showed that the T-A-G
      haplotype was associated with lower scores. CONCLUSIONS: These findings support
      the hypothesis that the LDAEP is also influenced by dopaminergic transmission.
      However, replications of these very preliminary but potentially important
      findings in independent samples are needed.

PMID- 18081003
TI  - NPC-db, a Niemann-Pick type C disease gene variation database.
AB  - Niemann-Pick type C (NPC) disease is a rare autosomal-recessive lysosomal storage
      disease typically accompanied by progressive impairment of nervous system and
      liver function. Biochemically, the disorder presents with an inhibited egress of
      cholesterol and glycosphingolipids from endosomal and lysosomal compartments in
      neuronal and nonneuronal cells. In the majority of NPC patients, mutations in the
      NPC1 gene can be identified. About 5% of patients show mutations in the NPC2
      gene. Many different mutations can cause NPC disease and multiple variants not
      associated with the disease are known in both genes. A continuously updated
      collection of gene variants is lacking to date and only limited information is
      available on genotype-phenotype correlation. We have created the NPC disease gene
      variation database (NPC-db; http://npc.fzk.de; last accessed 24 October 2007).
      This database aims to provide a comprehensive overview of the sequence variants
      in NPC1 and NPC2, including information on their functional consequences and
      associated haplotypes. Moreover, genotype data and clinical information from
      individual NPC patients provide information on the impact of functional variants.
      NPC-db addresses professionals and nonprofessionals dealing with NPC disease on a
      clinical, diagnostic, research, or personal basis. The user is encouraged to
      search contents and submit novel information, thereby contributing to generate a
      valuable open-access tool that will allow a better understanding of the molecular
      and clinical details of NPC disease.

PMID- 18081004
TI  - Repressing the neuron within.
AB  - A myriad of coordinated signals control cellular differentiation. Reprogramming
      the cell's proteome drives global changes in cell morphology and function that
      define cell phenotype. A switch in alternative splicing of many pre-mRNAs
      encoding neuronal-specific proteins accompanies neuronal differentiation. Three
      groups recently showed that the global splicing repressor, polypyrimidine track
      binding protein (PTB), regulates this switch.1-3 Although a subset of neuronal
      genes are turned on in both non-neuronal and neuronal cells, restricted
      expression of PTB in non-neuronal cells diverts their mRNAs to nonsense-mediated
      decay and prevents protein expression. When the PTB brake is released, the cell
      splices like a neuron.

PMID- 18081006
TI  - "JIP"ing along the axon: the complex roles of JIPs in axonal transport.
AB  - JIPs are JNK interacting proteins and bind to JNK cascade kinases. JIP1 and JIP3
      were known to be adaptors linking cargo to Kinesin-I, a major molecular motor for
      axonal transport. Recent research sheds further light on JIPs' complex roles in
      axonal transport, namely in activation of Kinesin-I and in cargo release. In
      Drosophila, APLIP1/JIP1 allows the Kinesin-I complex to enable cargo release
      through activation of JNK signaling.1 In mammalian cell culture, JIP1 is
      necessary and, together with UNC-76/FEZ1, sufficient for activating Kinesin-I.2 I
      discuss and compare the many roles played by JIP1 and JIP3 through interactions
      with several distinct players, in retrograde as well as anterograde transport.

PMID- 18081007
TI  - A shifting paradigm: histone deacetylases and transcriptional activation.
AB  - Transcriptional repression and silencing have been strongly associated with
      hypoacetylation of histones. Accordingly, histone deacetylases, which remove
      acetyl groups from histones, have been shown to participate in mechanisms of
      transcriptional repression. Therefore, current models of the role of acetylation
      in transcriptional regulation focus on the acetylation status of histones and
      designate histone acetyltransferases, which add acetyl groups to histones, as
      transcriptional coactivators and histone deacetylases as corepressors. In recent
      years, an accumulation of studies have shown that these enzymes also target non
      histone proteins and that histone deacetylases have clear roles as coactivators
      at a variety of genes, some of which are key regulators of cell growth and
      survival. This review summarizes the evidence for histone deacetylases as
      coactivators and provides models of coactivation mechanisms, some of which
      integrate roles of acetylated histones and non-histone proteins in transcription.

PMID- 18081005
TI  - Damage-induced reactivation of cohesin in postreplicative DNA repair.
AB  - Cohesin establishes sister-chromatid cohesion during S phase to ensure proper
      chromosome segregation in mitosis. It also facilitates postreplicative homologous
      recombination repair of DNA double-strand breaks by promoting local pairing of
      damaged and intact sister chromatids. In G2 phase, cohesin that is not bound to
      chromatin is inactivated, but its reactivation can occur in response to DNA
      damage. Recent papers by Koshland's and Sjogren's groups describe the critical
      role of the known cohesin cofactor Eco1 (Ctf7) and ATR checkpoint kinase in
      damage-induced reactivation of cohesin, revealing an intricate mechanism that
      regulates sister-chromatid pairing to maintain genome integrity.

PMID- 18081008
TI  - Calibration of the Andersen cascade impactor for the characterization of nasal
      products.
AB  - Current cascade impactor protocols do not completely rule out nasal preparations
      entering the lower respiratory tract. A modified cascade impactor (MCI) was
      developed to characterize the particle size fraction capable of deposition in the
      lower respiratory tract. This is an important measure of the potential for
      delivery to a site which is not the route of administration, and which could lead
      to potential toxicity. Monodisperse aerosols were utilized to calibrate the Stage
      -2 and Stage -0 of an Andersen Mk II nonviable cascade impactor at 15 L per
      minute flow rate. While these sampling conditions are beyond the normal working
      range of impactor theory in practice the instrument was shown to discriminate the
      designated particle sizes sampled. This novel setup extended the upper limit of
      the range of particle sizes that the cascade impactor can characterize from 8.7
      to 16.5 microm.

PMID- 18081009
TI  - Drosophila telomeres: an exception providing new insights.
AB  - Drosophila telomeres comprise DNA sequences that differ dramatically from those
      of other eukaryotes. Telomere functions, however, are similar to those found in
      telomerase-based telomeres, even though the underlying mechanisms may differ.
      Drosophila telomeres use arrays of retrotransposons to maintain chromosome
      length, while nearly all other eukaryotes rely on telomerase-generated short
      repeats. Regardless of the DNA sequence, several end-binding proteins are
      evolutionarily conserved. Away from the end, the Drosophila telomeric and
      subtelomeric DNA sequences are complexed with unique combinations of proteins
      that also modulate chromatin structure elsewhere in the genome. Maintaining and
      regulating the transcriptional activity of the telomeric retrotransposons in
      Drosophila requires specific chromatin structures and, while telomeric silencing
      spreads from the terminal repeats in yeast, the source of telomeric silencing in
      Drosophila is the subterminal arrays. However, the subterminal arrays in both
      species may be involved in telomere-telomere associations and/or communication.

PMID- 18081010
TI  - Alternative splicing: current perspectives.
AB  - Alternative splicing is a well-characterized mechanism by which multiple
      transcripts are generated from a single mRNA precursor. By allowing production of
      several protein isoforms from one pre-mRNA, alternative splicing contributes to
      proteomic diversity. But what do we know about the origin of this mechanism? Do
      the same evolutionary forces apply to alternatively and constitutively splice
      exons? Do similar forces act on all types of alternative splicing? Are the
      products generated by alternative splicing functional? Why is "improper"
      recognition of exons and introns allowed by the splicing machinery? In this
      review, we summarize the current knowledge regarding these issues from an
      evolutionary perspective.

PMID- 18081011
TI  - Right or left turn? RecA family protein filaments promote homologous
      recombination through clockwise axial rotation.
AB  - The RecA family proteins mediate homologous recombination, a ubiquitous mechanism
      for repairing DNA double-strand breaks (DSBs) and stalled replication forks.
      Members of this family include bacterial RecA, archaeal RadA and Rad51, and
      eukaryotic Rad51 and Dmc1. These proteins bind to single-stranded DNA at a DSB
      site to form a presynaptic nucleoprotein filament, align this presynaptic
      filament with homologous sequences in another double-stranded DNA segment,
      promote DNA strand exchange and then dissociate. It was generally accepted that
      RecA family proteins function throughout their catalytic cycles as right-handed
      helical filaments with six protomers per helical turn. However, we recently
      reported that archaeal RadA proteins can also form an extended right-handed
      filament with three monomers per helical turn and a left-handed protein filament
      with four monomers per helical turn. Subsequent structural and functional
      analyses suggest that RecA family protein filaments, similar to the F1-ATPase
      rotary motor, perform ATP-dependent clockwise axial rotation during their
      catalytic cycles. This new hypothesis has opened a new avenue for understanding
      the molecular mechanism of RecA family proteins in homologous recombination.

PMID- 18081015
TI  - Knowledge-making distinctions in synthetic biology.
AB  - Synthetic biology is an increasingly high-profile area of research that can be
      understood as encompassing three broad approaches towards the synthesis of living
      systems: DNA-based device construction, genome-driven cell engineering and
      protocell creation. Each approach is characterized by different aims, methods and
      constructs, in addition to a range of positions on intellectual property and
      regulatory regimes. We identify subtle but important differences between the
      schools in relation to their treatments of genetic determinism, cellular context
      and complexity. These distinctions tie into two broader issues that define
      synthetic biology: the relationships between biology and engineering, and between
      synthesis and analysis. These themes also illuminate synthetic biology's
      connections to genetic and other forms of biological engineering, as well as to
      systems biology. We suggest that all these knowledge-making distinctions in
      synthetic biology raise fundamental questions about the nature of biological
      investigation and its relationship to the construction of biological components
      and systems.

PMID- 18081012
TI  - Magnetic resonance imaging-based detection of glial brain tumors in mice after
      antiangiogenic treatment.
AB  - Proper delineation of gliomas using contrast-enhanced magnetic resonance imaging
      (CE-MRI) poses a problem in neuro-oncology. The blood brain barrier (BBB) in
      areas of diffuse-infiltrative growth may be intact, precluding extravasation and
      subsequent MR-based detection of the contrast agent gadolinium
      diethylenetriaminepenta-acetic acid (Gd-DTPA). Treatment with antiangiogenic
      compounds may further complicate tumor detection as such compounds can restore
      the BBB in angiogenic regions. The increasing number of clinical trials with
      antiangiogenic compounds for treatment of gliomas calls for the development of
      alternative imaging modalities. Here we investigated whether CE-MRI using
      ultrasmall particles of iron oxide (USPIO, Sinerem) as blood pool contrast agent
      has additional value for detection of glioma in the brain of nude mice. We
      compared conventional T1-weighted Gd-DTPA-enhanced MRI to T2*-weighted USPIO
      enhanced MRI in mice carrying orthotopic U87 glioma, which were either or not
      treated with the antiangiogenic compound vandetanib (ZD6474, ZACTIMA). In
      untreated animals, vessel leakage within the tumor and a relatively high tumor
      blood volume resulted in good MRI visibility with Gd-DTPA- and USPIO-enhanced
      MRI, respectively. Consistent with previous findings, vandetanib treatment
      restored the BBB in the tumor vasculature, resulting in loss of tumor
      detectability in Gd-DTPA MRI. However, due to decreased blood volume, treated
      tumors could be readily detected in USPIO-enhanced MRI scans. Our findings
      suggest that Gd-DTPA MRI results in overestimation of the effect of
      antiangiogenic therapy of glioma and that USPIO-MRI provides an important
      complementary diagnostic tool to evaluate response to antiangiogenic therapy of
      these tumors.

PMID- 18081016
TI  - Asymmetric nuclear reprogramming in somatic cell nuclear transfer?
AB  - Despite the progress achieved over the last decade after the birth of the first
      cloned mammal, the efficiency of reproductive cloning remains invariably low.
      However, research aiming at the use of nuclear transfer for the production of
      patient-tailored stem cells for cell/tissue therapy is progressing rapidly. Yet,
      reproductive cloning has many potential implications for animal breeding,
      transgenic research and the conservation of endangered species. In this article
      we suggest that the changes in the epi-/genotype observed in cloned embryos arise
      from unbalanced nuclear reprogramming between parental chromosomes. It is
      probable that the oocyte reprogramming machinery, devised for resident
      chromosomes, cannot target the paternal alleles of somatic cells. We, therefore,
      suggest that a reasonable approach to balance this asymmetry in nuclear
      reprogramming might involve the transient expression in donor cells of chromatin
      remodelling proteins, which are physiologically expressed during spermatogenesis,
      in order to induce a male-specific chromatin organisation in the somatic cells
      before nuclear transfer.

PMID- 18081017
TI  - From priming to plasticity: the changing fate of rhizodermic cells.
AB  - The fate of root epidermal cells is controlled by a complex interplay of
      transcriptional regulators, generating a genetically determined, position-biased
      arrangement of root hair cells. This pattern is altered during postembryonic
      development and in response to environmental signals to confer developmental
      plasticity that acclimates the plant to the prevailing conditions. Based on the
      hypothesis that events downstream of this initial mechanism can modulate the
      pattern installed during embryogenesis, we have developed a reaction diffusion
      model that reproduces the root hair patterning previously observed
      experimentally. Under all growth conditions, an almost equal spacing between root
      hair forming cells was observed both in vitro and in silico, indicating that long
      range intercellular communication is crucial for the trichoblasts' decision to
      form a root hair. We assume that a hair growth promoter (HGP) is upregulated in
      root-hair-forming cells by a trichoblast-specific component. Once established,
      HGP production is self-enhancing. The autocatalytic regulation of HGP is
      antagonized by an HGP-produced hair growth inhibitor (HGI). HGI is exported from
      trichoblasts and diffuses to neighboring cells, where it inhibits further HGP
      production and promotes the non-hair cell fate. Under conditions of phosphate
      deficiency, we hypothesise that HGP production is increased and HGI diffusion
      rate is reduced, leading to a position-independent formation of extra root hairs.

PMID- 18081020
TI  - The 7th UK Evolutionary Developmental Biology Meeting, 7th August 2007.

PMID- 18081019
TI  - Light resonance energy transfer-based methods in the study of G protein-coupled
      receptor oligomerization.
AB  - Since most of the functions in cells are mediated by multimeric protein
      complexes, the determination of protein-protein interactions is an important step
      in the study of cellular mechanisms. Traditionally, after screening for possible
      target interactors by means of a yeast two-hybrid screen, several methods are
      used to validate the initial result before carrying out functional experiments.
      Nowadays, non-invasive fluorescence-based methods like Bioluminescence Resonance
      Energy Transfer (BRET) and Fluorescence Resonance Energy Transfer (FRET) are
      widely used in the study of protein-protein interactions in living cells. In the
      present review, we address the individual strengths and weaknesses of both RET
      approaches, providing information on their possible future use in the study of G
      protein-coupled receptor oligomerization.

PMID- 18081021
TI  - DNA barcoding of animal species-response to DeSalle.

PMID- 18081023
TI  - Heritability of obsessive-compulsive symptom dimensions.
AB  - Recent research has shown that obsessive-compulsive symptoms (OCS) differ
      remarkably among patients and can be divided into several symptom dimensions. OCS
      are influenced by genetic components, but it is unknown to what extent these
      symptom dimensions are heritable. The phenotypic heterogeneity also raises the
      question to what extent the symptom dimensions are influenced by specific or
      shared genetic factors. We studied a population sample of 1,383 female twins from
      the Virginia Twin Registry. OCS was measured by a questionnaire with 20 items
      from the Padua Inventory. After factor analysis, three reliable OC symptom
      dimensions were retained: Rumination, Contamination, and Checking. These OC
      dimensions were analyzed with multivariate genetic models to investigate both the
      overlap and uniqueness of genetic and environmental contributions underlying OC
      symptom dimensions. The multivariate common pathway model provided the best
      description of the data. All symptom dimensions share variation with a latent
      common factor, that is, OC behavior. Variation in this common factor was
      explained by both genes (36%) and environmental factors (64%). Only the
      Contamination dimension was influenced by specific genes and seemed to be a
      relatively independent dimension. The results suggest that a broad OC behavioral
      phenotype exists, influenced by both genes and nonshared environment. In
      addition, we found evidence for specific genetic and environmental factors
      underlying the Contamination dimension. Use of the Contamination dimension could
      therefore provide a powerful approach for the detection of genetic susceptibility
      loci that contribute to OCS.

PMID- 18081024
TI  - Association study for genes at chromosome 5p13-q11 in attention deficit
      hyperactivity disorder.
AB  - Linkage of attention deficit hyperactivity disorder (ADHD) to the short arm
      centromeric region of chromosome 5 has been reported in multiple studies. The
      overlapping region (5p13-q11) contains a number of strong candidate genes for
      ADHD, based on their role in brain function or neurodevelopment. The aim of this
      study was to investigate some of the top candidates among these genes in relation
      to ADHD in a sample of 245 nuclear families from the Toronto area. We
      investigated the genes for the glial cell-derived neurotropic factor (GDNF), the
      fibroblast growth factor 10 (FGF10), islet-1 (ISL1), the hyperpolarized potassium
      channel (HCN1) and the integrin alpha 1 (ITGA1). In addition to these genes, we
      assessed the 3'region of the SLC1A3 gene, a glutamate transporter implicated in
      ADHD by a previous association study. A total of 36 polymorphisms were selected
      across the six genes. We performed family-based association and haplotype
      analyses. ADHD is a dimensional disorder, with symptoms of inattention and
      hyperactivity-impulsivity therefore, we also conducted quantitative analysis in
      relation to symptom scores for both dimensions. Single marker and haplotype
      analyses yielded little evidence of association for any of the genes tested in
      this study. Moreover, we were unable to replicate the positive association
      findings reported for SLC1A3. Our results suggest that these six genes are
      unlikely to be susceptibility genes in the chromosome 5p13-q11 region and other
      genes should now be considered for priority study.

PMID- 18081025
TI  - A first stage genome-wide screen for regions shared identical-by-descent in
      Hutterite families with multiple sclerosis.
AB  - The complexity of multiple sclerosis (MS) genetics has made the search for novel
      genes using traditional sharing methods problematic. In order to minimize the
      genetic heterogeneity present in the MS population we have screened the Canadian
      MS population for individuals belonging to the Hutterite Brethren. Seven
      Hutterites with clinically definite MS were ascertained and are related to a
      common founder by eight generations. Six of the 7 affected individuals and 21 of
      their unaffected family members (total = 27) were genotyped for 807 markers.
      Haplotypes were then inspected for sharing among the six MS patients. There were
      three haplotypes shared among all six MS patients. The haplotypes were located at
      2q34-35, 4q31-32, and 17p13. An additional 15 haplotypes were shared among five
      of the six Hutterites MS patients. The HLA Class II region was one of the
      highlighted regions; however, the shared MHC haplotype bore the DRB1*04 allele
      and not the MS-associated DRB1*15 allele providing further evidence of the
      complexity of the MHC. Additional genotyping to refine the haplotypes followed by
      screening for potential variants may lead to the identification of a novel MS
      susceptibility gene(s) in this unique population.

PMID- 18081026
TI  - A loss-of-function mutation in the FTSJ1 gene causes nonsyndromic X-linked mental
      retardation in a Japanese family.
AB  - Mental retardation (MR) is a common trait, affecting approximately 2-3% of
      individuals in the general population. Although the etiology of MR remains
      largely unknown, genetics apparently play a major role. Recent molecular studies
      of X-linked form of MR in European and North American countries have revealed 24
      nonsyndromic X-linked mental retardation (NS-XLMR) genes including FTSJ1, a human
      homolog of the Escherichia coli 2'-O-rRNA methyltransferase FtsJ/RrmJ gene. Here
      we identified a novel FTSJ1 mutation in an XLMR family through mutation screening
      of a cohort of 73 unrelated Japanese male probands with MR. Sequence analysis of
      the proband and his mother revealed a G > A substitution at the consensus for the
      donor splicing site in intron 8 (c.571 + 1G > A) of FTSJ1. This mutation
      prevented the removal intron 8 from the pre-mRNA, thereby leading to a frameshift
      in the mutant FTSJ1 mRNA and resulting in a premature termination in exon 9.
      Quantitative RT-PCR showed a significant reduction of mutant FTSJ1 mRNA in the
      patient's lymphoblast cells, which was restored by treatment with cycloheximide,
      a potent inhibitor of nonsense-mediated mRNA decay (NMD). Therefore, mRNAs
      carrying this mutation are likely subject to degradation by NMD. Together, loss
      of-function of FTSJ1 may be a mechanism for the cognitive dysfunction observed in
      this family. Our study also suggested that the FTSJ1 mutation probably accounts
      for XLMR in Japanese at a similar frequency (1-2%) as in Europeans.

PMID- 18081027
TI  - Linkage analysis of attention deficit hyperactivity disorder.
AB  - Results of behavioral genetic and molecular genetic studies have converged to
      suggest that both genes contribute to the development of ADHD. Although prior
      linkage studies have produced intriguing results, their results have been
      inconsistent, with no clear pattern of results emerging across studies. We
      genotyped 5,980 SNPs across the genome in 1,187 individuals from families with
      children diagnosed with ADHD. We then performed two nonparametric linkage
      analyses on ADHD families: (1) an affected sibling pair linkage analysis on 217
      families with 601 siblings diagnosed with ADHD and (2) a variance components
      linkage analysis using the number of ADHD symptoms as the phenotype on 260
      families with 1,100 phenotyped siblings. The affection status linkage analysis
      had a maximum LOD score of 1.85 on chromosome 8 at 54.2 cM. The maximum LOD score
      in the variance components linkage analysis was 0.8 on chromosome 8 at 93.4 cM.
      The absence of regions of significant or suggestive linkage in these data suggest
      that there are no genes of large effect contributing to the ADHD phenotype.

PMID- 18081028
TI  - The -1021 C/T DBH polymorphism is associated with neuropsychological performance
      among children and adolescents with ADHD.
AB  - Catecholaminergic imbalance has increasingly been implicated in the
      pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The enzyme
      dopamine-beta-hydroxylase (D beta H)-critical to catecholaminergic regulation-is
      under strong genetic control, with the -1021 C/T polymorphism accounting for up
      to 50% of the enzymatic activity. This work aimed to investigate association
      between this functional polymorphism and the performance of children and
      adolescents with ADHD in neuropsychological measures of executive function (EF).
      Sixty-four drug-naive patients with ADHD undertook a Continuous Performance Test
      and the Wisconsin Card Sorting Test. By means of a factorial analysis, a
      composite measure of EF was extracted. Performance according to genotypic group
      was analyzed, including age as a confounder. In addition, a family-based
      association test was conducted as a confirmatory analysis. Principal components
      analysis of neuropsychological measures loaded two factors that explained 83.8%
      of total variance. Cognitive performance, as measured by the composite score,
      showed significant difference between genotypic groups after adjustment for age
      (P = 0.002). The CC homozygosity was associated with a diminished global EF
      performance, a result that was corroborated by the intra-familial analysis. The
      present study demonstrated an association between the neuropsychological
      performance of children with ADHD and a functional polymorphism in the promoter
      region of the DBH gene. The refinement of the ADHD phenotype by means of
      composite measures of EF can contribute to uncover the molecular underpinnings of
      ADHD.

PMID- 18081029
TI  - Up-regulation of ADM and SEPX1 in the lymphoblastoid cells of patients in
      monozygotic twins discordant for schizophrenia.
AB  - The contribution of genetic factors to schizophrenia is well established and
      recent studies have indicated several strong candidate genes. However, the
      pathophysiology of schizophrenia has not been totally elucidated yet. To date,
      studies of monozygotic twins discordant for schizophrenia have provided insight
      into the pathophysiology of this illness; this type of study can exclude inter
      individual variability and confounding factors such as effects of drugs. In this
      study we used DNA microarray analysis to examine the mRNA expression patterns in
      the lymphoblastoid (LB) cells derived from two pairs of monozygotic twins
      discordant for schizophrenia. From five independent replicates for each pair of
      twins, we selected five genes, which included adrenomedullin (ADM) and
      selenoprotein X1 (SEPX1), as significantly changed in both twins with
      schizophrenia. Interestingly, ADM was previously reported to be up-regulated in
      both the LB cells and plasma of schizophrenic patients, and SEPX1 was included in
      the list of genes up-regulated in the peripheral blood cells of schizophrenia
      patients by microarray analysis. Then, we performed a genetic association study
      of schizophrenia in the Japanese population and examined the copy number
      variations, but observed no association. These findings suggest the possible role
      of ADM and SEPX1 as biomarkers of schizophrenia. The results also support the
      usefulness of gene expression analysis in LB cells of monozygotic twins
      discordant for an illness.

PMID- 18081030
TI  - On the necessity for animal experimentation.

PMID- 18081032
TI  - Potential of dendritic-cell immunotherapy for relapse after allogeneic
      hematopoietic stem cell transplantation, shown by WT1 peptide- and keyhole-limpet
      hemocyanin-pulsed, donor-derived dendritic-cell vaccine for acute myeloid
      leukemia.
AB  - Induction of leukemia-specific immune responses is a promising treatment for
      acute myeloid leukemia. A 58-year-old woman received Wilms' tumor 1 (WT1) peptide
      and keyhole limpet hemocyanin (KLH)-pulsed, donor-derived dendritic cell (DC)
      vaccination for AML relapse after allogeneic stem cell transplantation. The
      vaccination induced immune responses to the naive antigen KLH, whereas definitive
      immune responses to WT1 were not detected. Leukemia gradually progressed despite
      of vaccination. This study indicates that DC vaccination can induce an antigen
      specific immune response in a patient after allogeneic stem cell transplantation,
      thus representing a viable strategy to induce antigen-specific immune responses
      in such patients.

PMID- 18081033
TI  - Happy authors!

PMID- 18081034
TI  - Chemokine receptor 4 (CXCR4) is part of the lipopolysaccharide "sensing
      apparatus".
AB  - Recognition of bacterial lipopolysaccharide (LPS) by the innate immune system
      involves at least three receptor molecules: CD14, TLR4 and MD-2. Additional
      receptor components such as heat shock proteins, chemokine receptor 4 (CXCR4), or
      CD55 have been suggested to be part of this activation cluster; possibly acting
      as additional LPS transfer molecules. Our group has previously identified CXCR4
      as a component of the "LPS-sensing apparatus". In this study we aimed to
      elucidate the role that CXCR4 plays in innate immune responses to LPS. Here we
      demonstrate that CXCR4 transfection results in responsiveness to LPS.
      Fluorescence correlation spectroscopy experiments further showed that LPS
      directly interacts with CXCR4. Our data suggest that CXCR4 is not only involved
      in LPS binding but is also responsible for triggering signalling, especially
      mitogen-activated protein kinases in response to LPS. Finally, co-clustering of
      CXCR4 with other LPS receptors seems to be crucial for LPS signalling, thus
      suggesting that CXCR4 is a functional part of the multimeric LPS "sensing
      apparatus".

PMID- 18081035
TI  - Neonatal CD8+ T cells are slow to develop into lytic effectors after HSV
      infection in vivo.
AB  - HSV is an important neonatal pathogen. We defined the kinetics of the primary CTL
      response to HSV-2 in vivo in neonatal mice. Using a replication-defective HSV-2
      virus, we demonstrate that neonates mount a primary HSV-specific CTL effector
      response in the draining LN, with delayed onset and shortened peak activity, in
      contrast to the rapid, strong response observed in adult mice. The shortened peak
      neonatal CTL response is independent of HSV dose and is associated with retarded
      CD8(+) T cell expansion, reduced expansion of HSV-specific tetramer-positive
      CD8(+) T cells and a reduced CD8(+) T cell IFN-gamma response. Paradoxically,
      neonatal CD8(+) T cells display enhanced non-specific early activation that is
      not sustained. Neonatal HSV-specific TCR-transgenic CD8(+) T cells showed reduced
      proliferation in vivo when transferred into HSV-infected neonatal mice compared
      to adult T cell controls. Our data suggest that early events in CD8(+) T cell
      priming underlie the attenuated newborn CTL response to HSV.

PMID- 18081036
TI  - c-FLIP(S) reduces activation of caspase and NF-kappaB pathways and decreases T
      cell survival.
AB  - Effective stimulation of NF-kappaB in T cells following TCR ligation requires the
      activity of caspase-8. The active caspase-8 complex includes the paracaspase,
      MALT1, and Bcl-10, which connect to the NF-kappaB pathway. It has been less clear
      what regulates the level of caspase-8 activity during T cell activation. A likely
      candidate is cellular FLIP (c-FLIP), an enzymatically inert caspase-8 homologue.
      Two alternatively spliced forms of c-FLIP exist, a long form (c-FLIP(L)) and a
      short-form (c-FLIP(S)). The latter lacks the C-terminal caspase-like domain. c
      FLIP(L) can heterodimerize with and activate caspase-8 through an activation loop
      in the C terminus of c-FLIP(L). Here we show that, in contrast to c-FLIP(L), c
      FLIP(S) inhibits activation of caspase-8 in T cells, and consequently reduces
      recruitment of MALT1 and Bcl-10 to the active caspase complex. This results in
      reduced activity of NF-kappaB. Consequently, T cells from c-FLIP(S)-transgenic
      mice undergo more rapid cell death both spontaneously and after activation. The
      findings suggest that c-FLIP(S) functions to reduce the expansion of T cells
      during an immune response.

PMID- 18081037
TI  - Efficient induction of mucosal and systemic immune responses by virus-like
      particles administered intranasally: implications for vaccine design.
AB  - Intranasal (i.n.) immunization aims to induce local as well as systemic immune
      responses. In the present study, we assessed a vaccine platform based on virus
      like particles (VLP) derived from the RNA phage Qbeta for i.n. immunization. We
      found that both i.n. and subcutaneous (s.c.) administration of Qbeta-VLP elicited
      strong and comparable specific IgG responses in serum and lung. Surprisingly,
      both routes also induced high levels of specific IgA in serum. In contrast, only
      i.n. administration of Qbeta-VLP resulted in local IgA production in the lung.
      Efficient induction of B cell responses by i.n. administration of VLP was further
      supported by the presence of large numbers of germinal centers (GC) as well as
      memory B cells in the spleen and plasma cells in the bone marrow. Results
      obtained for the VLP itself could be extended to an antigen covalently attached
      to it. Specifically, i.n. immunization of mice with VLP displaying the influenza
      virus derived ectodomain of the M2 protein resulted in strong M2-specific
      antibody responses as well as anti-viral protection. In contrast, i.n.
      immunization with VLP displaying p33 peptide, the major CTL epitope of
      lymphocytic choriomeningitis virus, induced relatively inefficient cytotoxic T
      cell responses, resulting in low numbers of specific T cells and poor effector
      cell differentiation. Taken together, these results suggest that effective
      antibody-based vaccines are achievable by i.n. administration of Qbeta-VLP
      displaying specific antigens.

PMID- 18081039
TI  - Characterization of a subset of antigen-specific human central memory CD4+ T
      lymphocytes producing effector cytokines.
AB  - CCR7(+ )central memory (T(CM)) CD4(+) T cells play a central role in long-term
      immunological memory. Recent reports indicate that a proportion of CD4(+) T(CM)
      is able to produce effector cytokines. The phenotype and the role of this subset
      remain unknown. We characterized cytokine-producing human CD4(+) T(CM) specific
      for cleared protein and persistent viral Ag. Our results demonstrate that the
      type of Ag stimulation is a major determinant of CD4(+) T(CM) differentiation.
      CMV-specific T(CM) were significantly more differentiated than protein Ag
      specific T(CM) and included higher proportions of IFN-gamma-producing cells. The
      expression of killer cell lectin-like receptor G1 (KLRG1) by protein Ag- and CMV
      specific T(CM) was associated with increased production of effector cytokines.
      KLRG1(+) T(CM) expressed high levels of CD127, suggesting that they can survive
      long term under the influence of IL-7. The induction of KLRG1(+) T(CM) may
      therefore represent an important target of vaccination against pathogens
      controlled by cellular immune responses.

PMID- 18081038
TI  - Increased TLR responses in dendritic cells lacking the ITAM-containing adapters
      DAP12 and FcRgamma.
AB  - The inhibitory effect of DAP12 on macrophages has been revealed by examining
      myeloid cells from DAP12-deficient mice. In this report, we demonstrate that both
      DAP12 and the FcepsilonRIgamma-chain (FcRgamma) are required for negative
      regulation of TLR responses in bone marrow-derived dendritic cells (DC). Loss of
      both DAP12 and FcRgamma enhanced the pro-inflammatory cytokine production and
      maturation of DC after TLR stimulation, resulting in a greater percentage of DC
      that produced IL-12 p40, TNF, and IL-6, and expressed high levels of MHC class
      II, CD80, and CD86. Whereas DC lacking only DAP12 showed some increased TLR
      responses, those lacking only FcRgamma had a greater enhancement of maturation
      and cytokine production, though to a lesser extent than DC lacking both DAP12 and
      FcRgamma. Additionally, antigen-specific T cell proliferation was enhanced by
      DAP12(-/-)FcRgamma(-/-) DC relative to wild-type DC after maturation. Similar to
      DAP12(-/-)FcRgamma(-/-) DC, Syk-deficient DC also had increased inflammatory
      cytokine production, maturation, and antigen presentation. These results confirm
      the inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM)
      signaling in myeloid cells and show that DC and macrophages differ in their
      dependence on the ITAM-containing adapters DAP12 and FcRgamma for negative
      regulation of TLR signaling.

PMID- 18081041
TI  - Broad T cell immunity to the LcrV virulence protein is induced by targeted
      delivery to DEC-205/CD205-positive mouse dendritic cells.
AB  - There is a need for a more efficient vaccine against the bacterium Yersinia
      pestis, the agent of pneumonic plague. The F1-LcrV (F1-V) subunit vaccine in
      alhydrogel is known to induce humoral immunity. In this study, we utilized DC to
      investigate cellular immunity. We genetically engineered the LcrV virulence
      protein into the anti-DEC-205/CD205 mAb and thereby targeted the conjugated
      protein directly to mouse DEC-205(+) DC in situ. We observed antigen-specific
      CD4(+) T cell immunity measured by intracellular staining for IFN-gamma in three
      different mouse strains (C57BL/6, BALB/c, and C3H/HeJ), while we could not
      observe such T cell responses with F1-V vaccine in alhydrogel. Using a peptide
      library for LcrV protein, we identified two or more distinct CD4(+) T cell
      mimetopes in each MHC haplotype, consistent with the induction of broad immunity.
      When compared to nontargeted standard protein vaccine, DC targeting greatly
      increased the efficiency for inducing IFN-gamma-producing T cells. The targeted
      LcrV protein induced antibody responses to a similar extent as the F1-V subunit
      vaccine, but Th1-dependent IgG2a and IgG2c isotypes were observed only after anti
      DEC-205:LcrV mAb immunization. This study sets the stage for the analysis of
      functional roles of IFN-gamma-producing T cells in Y. pestis infection.

PMID- 18081040
TI  - Identification of murine B cell lines that undergo somatic hypermutation focused
      to A:T and G:C residues.
AB  - Activation-induced deaminase (AID) is the master regulator of class switch
      recombination (CSR) and somatic hypermutation (SHM), but the mechanisms
      regulating AID function are obscure. The differential pattern of switch plasmid
      activity in three IgM(+)/AID(+) and two IgG(+)/AID(+) B cell lines prompted an
      analysis of global gene expression to discover the origin of these cells. Gene
      profiling suggested that the IgG(+)/AID(+) B cell lines derived from germinal
      center B cells. Analysis of SHM potential demonstrates that the IgVkappa domains
      are inducibly diversified at high rate during in vitro culture. The mutation
      spectra focused to A:T base pairs, revealing a component of the hypermutation
      program that occurs preferentially during phase 2 of SHM. The A:T error spectra
      were analyzed and were not characteristic of polymerase eta activity. A
      differential pattern of three consensus motifs used for A:T base substitutions
      was observed in WT and Poleta-, Msh2- and Msh6-deficient B cells. Strikingly,
      mutations in our B cell lines recapitulated the mutable motif profile for Poleta
      and Msh2 deficiency, respectively, and suggest that an additional pathway for the
      generation of A:T mutations in SHM is conserved in mouse and human.

PMID- 18081042
TI  - The strength of T cell stimulation determines IL-7 responsiveness, secondary
      expansion, and lineage commitment of primed human CD4+IL-7Rhi T cells.
AB  - Mouse memory T cell precursors express IL-7 receptor-alpha (IL-7R), proliferate
      with homeostatic cytokines and undergo secondary expansions with antigen. Here,
      we analyzed how the strength of antigenic stimulation regulates IL-7R expression,
      cytokine responsiveness and expansion potential of DC-primed human CD4(+ )T
      cells. IL-7R expression on proliferating T cells was highest at intermediate
      strength of stimulation, and purified CCR7(+)IL-7R(hi) and CCR7(-)IL-7R(lo)
      subsets had characteristics of memory and effector cells, respectively. However,
      CCR7(+)IL-7R(hi) cells generated under different priming conditions had
      strikingly different properties. Thus, increasing strength of stimulation
      promoted IL-7 responsiveness that correlated with reduced phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN) expression and enhanced s6 kinase
      activation, suggesting a tunable IL-7R coupling to PI3 kinase-dependent signaling
      pathways. Furthermore, functional and gene expression analysis revealed that
      intermediate-stimulated CCR7(+)IL-7R(hi) cells were similar to non-polarized
      central memory cells with high expansion potential. Conversely, high-stimulated
      CCR7(+)IL-7R(hi) cells shared characteristics with circulating pre-Th1 cells and
      differentiated spontaneously to Th1 effector cells. These results show that the
      strength of stimulation determines properties of activated IL-7R(hi) T cells, and
      suggest that memory T cell subsets could be derived from CCR7(+) precursors that
      received different strengths of stimulation.

PMID- 18081043
TI  - Long-term maternal imprinting of the specific B cell repertoire by maternal
      antibodies.
AB  - Maternal antibodies protect newborns whilst they are immunologically immature.
      This study shows that maternal antibodies can also shape the B cell repertoire of
      the offspring long after the maternal antibodies themselves become undetectable.
      V(H)DJ(H) gene-targeted (VI10) mice expressing a heavy chain specific for
      vesicular stomatitis virus (VSV) produce a 20-fold increased spontaneous titer of
      VSV-neutralizing antibodies. When transferred from mother to offspring, these
      antibodies prevented accumulation of Ag-specific transitional type 2 and marginal
      zone B cells with an activated phenotype and favored selection to the B cell
      follicles. This effect was B cell-intrinsic and lasted up to adulthood. The pups
      nursed by mothers producing specific antibodies developed higher endogenous
      antibody titers of this specificity which perpetuated the effects of specific B
      cell selection into the mature follicular compartment, presumably by blocking
      auto-Ag-dependent development of transitional type 2 B cells in the spleen. This
      repertoire change was functional, as following infection of adult mice with VSV,
      those pups that had received specific maternal antibodies as neonates had
      increased pre-immune titers and mounted strong early IgG neutralizing antibodies.

PMID- 18081044
TI  - [Influenza vaccination for medical personnel].

PMID- 18081045
TI  - [Recommendations of the Vaccine Standards Commission of the Robert Koch
      Institute].

PMID- 18081046
TI  - [The Nobel Prize for the creation of the knockout mouse].

PMID- 18081047
TI  - [Vaccination against Alzheimer's disease?].

PMID- 18081048
TI  - [Vaccination sceptics--vaccination opponents].

PMID- 18081049
TI  - [HIV--vaccine study failures].

PMID- 18081050
TI  - [Vaccination for travel].

PMID- 18081051
TI  - [Vaccination against human papillomavirus. An new prevention strategy against
      cancer].

PMID- 18081053
TI  - [Trends in vaccine development].

PMID- 18081055
TI  - [Statement of accounts].

PMID- 18081057
TI  - [Helping ourselves to promote our scientific advancement].

PMID- 18081065
TI  - Dynamic skin cooling with an environmentally compatible alternative cryogen
      during laser surgery.
AB  - BACKGROUND AND OBJECTIVES: Cryogen spray cooling with tetrafluoroethane (R134a)
      has been used to enhance epidermal protection during dermatologic laser surgery.
      However, R134a has a very high global warming potential (GWP = 1300). Our
      objective was to evaluate the cooling effectiveness of an alternative cryogen
      with a much lower GWP, namely liquid carbon dioxide (CO(2), GWP = 1). STUDY
      DESIGN/MATERIALS AND METHODS: A thin-film thermocouple deposited on an epoxy skin
      phantom was used to measure surface temperature (T(s)) variations induced by
      R134a or CO(2) sprays. The temperature distribution in the skin phantom was
      estimated using T(s) and Duhamel's method. Impact pressure and noise level of
      both cryogen sprays were measured with a dynamic sensor and sound meter,
      respectively. Consumption of both cryogens was also evaluated. RESULTS: For R134a
      sprays, T(s) was kept almost constant after 15 milliseconds. For CO(2) sprays,
      T(s) decreased continuously during the entire spurt of 50 milliseconds. The
      minimum T(s) induced by the CO(2) sprays was lower than that induced by R134a
      when the spurt duration was longer than 35 milliseconds. Numerical simulation
      shows that CO(2) sprays were able to induce very similar temperature reductions
      in the skin phantom as compared to R134a sprays when the spurt duration and delay
      time were selected appropriately. R134a sprays induced an impact pressure of 3.6
      kPa, as compared to 43.1 kPa for CO(2) sprays. The maximum noise level for R134a
      sprays was 109 dBA as compared to 135 dBA for the CO(2) sprays. The R134a
      consumption for a 50 milliseconds spurt is 67 mg as compared to 225 mg for a
      CO(2) spurt of the same duration. CONCLUSIONS: CO(2) sprays are expected to have
      similar skin cooling efficacy as R134a sprays. Although the CO(2) consumption is
      higher than R134a, its contribution to global warming is still much less than
      R134a. The effects of varying spurt durations on in vivo human skin and the
      impact on cutaneous blood flow require further investigation.

PMID- 18081066
TI  - Photodynamic inactivation of Enterococcus faecalis in dental root canals in
      vitro.
AB  - BACKGROUND AND OBJECTIVES: We previously reported the use of a flexible fiber
      optic that uniformly distributed light in the root canal space for targeting
      bacteria after their sensitization with methylene blue (MB). In the present
      study, we investigated the photodynamic effects of MB on Enterococcus faecalis
      species in experimentally infected root canals of extracted teeth after their
      sensitization with a concentration of MB that exhibits reduced dark toxicity.
      STUDY DESIGN/MATERIALS AND METHODS: In a model of root canal infection, 64 root
      canal specimens were prepared from extracted, single-rooted teeth and inoculated
      with E. faecalis (ATCC 29212). Three days later root canal infection was
      confirmed by scanning electron microscopy. The root canal systems were then
      incubated with 6.25 microg/ml MB for 5 minutes followed by exposure to light at
      665 nm (60 J/cm(2)) that was delivered from a diode laser via a fiber optic with
      a diameter of 500 microm. Following photodynamic therapy (PDT) the canal content
      was sampled by flushing the root canals, serially diluted and cultured on blood
      agar. Survival fractions were calculated by counting colony-forming units. High
      performance liquid chromatography (HPLC) was employed to determine the porphyrins
      content of E. faecalis. RESULTS: Scanning electron microscopy confirmed the
      presence of bacteria in the root canal system. PDT achieved 77.5% reduction of E.
      faecalis viability. MB alone and light alone reduced bacterial viability by 19.5%
      and 40.5%, respectively. HPLC did not reveal any porphyrin patterns expressed by
      E. faecalis. CONCLUSION: The results of this study support the need to determine
      the optimum MB concentration and light parameters to maximize bacterial killing
      in root canals.

PMID- 18081069
TI  - TEM/local excision: indications, techniques, outcomes, and the future.
AB  - Transanal endoscopic microsurgery (TEM) has emerged as a safe method for excising
      virtually any rectal adenoma and carefully selected cancers. Extended
      applications include treatment of extra- and supra-sphincteric fistulae,
      rectovaginal fistulae, anastomotic strictures, and sinus tracts. The procedure
      utilizes an air-tight system, long shafted instruments, high-quality magnifying
      optics, and constant carbon dioxide insufflation, all of which facilitate a
      precise excision and closure with clear margins. Complications are few, most
      patients can be treated as an outpatient.

PMID- 18081072
TI  - [The history of active immunization. Prevention is better than healing].

PMID- 18081075
TI  - [The immunologic basis of vaccination. Hightech training for the immune system].

PMID- 18081076
TI  - [Production and quality control of vaccines].

PMID- 18081078
TI  - [Death of a vaccine--the fall of LYMErix].

PMID- 18081080
TI  - [An oral vaccine against rotavirus-caused gastroenteritis].

PMID- 18081081
TI  - [Adjuvants for human vaccines].

PMID- 18081082
TI  - Microcalorimetric and spectroscopic investigation of the antibacterial properties
      of cationic ytterbium(III)-porphyrin complexes lacking charged peripheral groups.
AB  - The antibacterial activities towards Escherichia coli of two cationic Yb(III)
      monoporphyrin complexes, [Yb(III)(TMP)(H2O)3]Cl (1) and [Yb(III)(TTP)(H2O)3]Cl
      (2), were investigated at the cellular and sub-cellular levels. The biological
      effects of the complexes on the growth of E. coli were evaluated by
      microcalorimetry and by analysis of the resulting metabolic thermogenic curves,
      from which IC50 values and metabolic parameters such as growth rate and
      generation time were derived. At the subcellular level, DNA-binding experiments
      were performed by means of UV/VIS- and fluorescence-titration experiments, as
      well as by near-infrared (NIR) emission, which revealed that 1 and 2 strongly
      bind to herring-sperm DNA (HS-DNA), though by different binding modes.

PMID- 18081083
TI  - Hoogsteen vs. Watson-Crick base pairing: incorporation of 2-substituted adenine-
      and 7-deazaadenine 2'-deoxy-beta-D-ribonucleosides into oligonucleotides.
AB  - Various 2-substituted 2'-deoxyadenosines and 7-deazaadenosines have been
      synthesized. The phosphonate building block 9 of 2-chloro-7-deaza-2'
      deoxyadenosine (7-deazacladribine; 2) was prepared by 4,4'-dimethoxytritylation
      of the parent nucleoside (-->7), followed by protection of the amino function
      with a formamidine residue (-->8). The latter was reacted with PCl3/N
      methylmorpholine/1,2,4-triazole to give compound 9. Moreover, 2-methoxy-2'
      deoxyadenosine (2'-deoxyspongosine; 1b) was converted into the fully protected
      derivative 12, which was then transformed into the 2-cyanoethyl phosphoramidite
      14. Also the 2-(trifluoromethyl)-substituted 2'-deoxyadenosines 19-21 were
      prepared by glycosylation of the chromophore 16 with the halogenose 17, followed
      by one-pot deprotection and nucleophilic displacement of the 6-Cl substituent.
      The new DNA building blocks 9 and 14 were used--together with formerly prepared
      cladribine derivative 4--for solid-phase synthesis of a series of
      oligodeoxyribonucleotides. These were studied with respect to their thermal
      stability as well as of the base pairing mode (Watson-Crick vs. Hoogsteen) of
      modified bases.

PMID- 18081084
TI  - Synthesis and antifungal activity of aromatic bis-gamma-lactones analogous to
      avenaciolide.
AB  - Avenaciolide is a bis-gamma-lactone isolated from Aspergillus avenaceus and
      possesses antifungal activity. Here, we describe the total syntheses and
      characterization by elemental analyses, and IR and NMR spectroscopy of three new
      bis-gamma-lactones analogous to avenaciolide, where the octyl group of the
      natural product was replaced by aromatic groups. The effects of the avenaciolide,
      the novel compounds, and their synthetic precursors on the mycelia development
      and conidia germination of Colletotrichum gloeosporioides were evaluated in
      vitro. The new compounds were as active as avenaciolide in the tested conditions,
      while the synthetic precursors were inactive. The preparation and
      characterization of 15 new synthetic intermediates are also described.

PMID- 18081085
TI  - Acute toxicity of the water-soluble fraction of spent lubricating oil on the
      African catfish Clarias gariepinus.
AB  - Static tests were employed to assess the acute toxicity of the water-soluble
      fraction (WSF) of spent automotive lubricating oil (of mixed SAE grades) on
      Clarias gariepinus, a freshwater fish commonly cultured in Nigeria. Median lethal
      concentrations (LC50) of the WSF were found to decrease as a function of exposure
      time from 690+/-21 (after 24 h) to 513+/-58 mg/l (after 96 h). The
      characteristics of the WSF such as mean acidity (pH 6.6), turbidity (40 NTU),
      total dissolved solids (TDS; 40 mg/l) and significantly reduced (P<0.05)
      dissolved-oxygen (DO) values (1.44 mg/l) were not compliant with existing
      standards set for discharged effluents. The solubility of the detected straight
      chain aliphatics ranked as C14>C16>C32>C18>C28; that of the simple aromatics was
      ortho-xylene>para-xylene; and that of the polyaromatic hydrocarbons (PAHs) was
      acenaphthylene>9H
      fluorene>naphthalene>anthracene>phenanthrene>chrysene>benzo[k]fluoranthene>benzo[
      ]pyrene>benzo[b]fluoranthene, most of which being serious carcinogens. These oil
      constituents and the overall physico-chemical properties of the WSF are expected
      to act synergistically on the test organism (C. gariepinus), eliciting the
      quantal responses observed. The toxicity of the WSF points to the base
      constituent, oxidative degradation, and mechano-chemical reactions associated
      with aged crankcase oils. These oils, therefore, should definitely no longer be
      disposed into water streams or landscape, not even at sub-lethal concentrations,
      because of the inherent toxicity of their soluble fractions and the associated
      danger of bioaccumulation.

PMID- 18081086
TI  - Evolution of 'ligand-diffusion chreodes' on protein-surface models: a genetic
      algorithm study.
AB  - Lattice models have been previously used to model ligand diffusion on protein
      surfaces. Using such models, it has been shown that the presence of pathways (or
      'chreodes') of consecutive residues with certain properties can decrease the
      number of steps required for the arrival of a ligand at the active site. In this
      work, we show that, based on a genetic algorithm, ligand-diffusion pathways can
      evolve on a protein surface, when this surface is selected for shortening the
      travel length toward the active site. Biological implications of these results
      are discussed.

PMID- 18081087
TI  - Microbial transformation of spirolaxine, a bioactive undecaketide fungal
      metabolite from the basidiomycete Sporotrichum laxum.
AB  - Incubation of (+)-spirolaxine (= (3R)-5-hydroxy-7-methoxy-3-{5-[(2R,5R,7R)-2
      methyl-1,6-dioxaspiro[4.5]dec-7-yl]pentyl}-2-benzofuran-1(3H)-one; 1a) with
      Bacillus megaterium afforded two new mono- and one new dihydroxylated
      metabolite(s), all OH groups being introduced on the non-activated six-membered
      ring. In contrast, exposure of 1a to Cunninghamella echinulata gave rise to
      hydroxylation on the five-membered ring of the parent structure. The structures
      and absolute configurations of the new products 1b-e were deduced on the basis of
      MS and NMR data. The metabolite 1b was investigated, in comparison to 1a, for its
      cytotoxicity (sulforhodamin-B test) and for its antiproliferative activity
      towards bovine microvascular endothelial cells (BMEC).

PMID- 18081088
TI  - Spectroscopic analysis of the binding interaction between tinidazole and bovine
      serum albumin (BSA).
AB  - The interaction between bovine serum albumin (BSA) and tinidazole (Tindamax; 1)
      in aqueous solution was investigated in detail by means of UV/VIS and
      fluorescence spectroscopy, as well as through resonance light-scattering (RLS)
      spectroscopy. The apparent binding constant and number of binding sites were
      determined at three different temperatures, as well as the average binding
      distances between 1 and the nearest amino acid residue(s) of BSA, as analyzed by
      means of Forster's theory of non-radiation energy transfer. Compound 1 was found
      to quench the inner fluorescence of BSA by forming a tight 1:1 aggregate, based
      on both static quenching and non-radiation energy transfer. The entropy change
      upon complexation was positive, and the enthalpy change was negative, indicating
      that the observed spontaneous binding is mainly driven by electrostatic
      interactions.

PMID- 18081089
TI  - Transcription-inhibition and antitumor activities of N-alkylated
      tetraazacyclododecanes.
AB  - A series of alkyl-substituted tetraazacyclododecane congeners were synthesized,
      and their antitumor activities towards human HeLa cells as well as their effect
      on the in vitro transcription with T7 RNA polymerase were investigated. A
      structure-activity-relationship (SAR) study identified the most-active congeners
      as those with medium alkyl-chain lengths. Three compounds, 5-7, were found to
      exhibit significant biological activities, with IC50 values towards HeLa cells in
      the low-micromolar range.

PMID- 18081090
TI  - Synthesis of oligonucleotides carrying 5'-5' linkages using copper-catalyzed
      cycloaddition reactions.
AB  - There is considerable interest in coupling oligonucleotides to molecules and
      surfaces. Although amino- and thiol-containing oligonucleotides are being
      successfully used for this purpose, cycloaddition reactions may offer greater
      advantages due to their higher chemoselectivity and speed. In this study, copper
      catalyzed 1,3-dipolar cycloaddition reactions between oligonucleotides carrying
      azido and alkyne groups are examined. For this purpose, several protocols for the
      preparation of oligonucleotides carrying these two groups are described. The non
      templated chemical ligation of two oligonucleotides via copper-catalyzed [3+2]
      cycloaddition is described. By solid-phase methodology, oligonucleotides carrying
      5'-5' linkages can be obtained in good yields.

PMID- 18081091
TI  - Two new antibacterial sesquiterpenoids from Centipeda minima.
AB  - Two new guaiane-type sesquiterpene lactones, compounds 1 and 2, along with three
      known guaianolide- or pseudoguaianolides, were isolated from Centipeda minima
      (whole plant). Their structures were identified by spectroscopic and mass
      spectrometric analyses. The configuration at C5 of the guaiane framework of 1 was
      rationalized by quantum-mechanical calculations (Table 2). All compounds were
      found to be active against eight different microbial pathogens (Table 3), with
      MIC values in the range of 6.25-100 microg/ml.

PMID- 18081092
TI  - Qualitative and quantitative HPLC/MS determination of proanthocyanidins in areca
      nut (Areca catechu).
AB  - Proanthocyanidins (PACs) in areca nut (Areca catechu L.) were analyzed by high
      performance liquid chromatography (HPLC) combined with electrospray-ionization
      mass spectrometry (ESI-MS) and compared to grape seed extract. Under optimized
      conditions, the separated PACs were individually analyzed and identified on the
      basis of their [M+H]+ peaks. The PAC distribution in areca nut was found to be
      very similar to that in grape seed, but lacking any gallate conjugates. Based on
      reverse-phase HPLC separation, the PAC monomers (+)-catechin (CA, 1) and (-)
      epicatechin (EC; 2) were successfully quantified by ESI-MS in the selected-ion
      monitoring (SIM) mode, (-)-epigallocatechin (EGC; 3) being used as internal
      standard. Detailed quality and validation assays showed that the accuracy and
      repeatability (n = 8) were within 10% for each analyte.

PMID- 18081093
TI  - Solid-phase total synthesis and antimicrobial activities of loloatins A-D.
AB  - The first total synthesis of the decapeptide antibiotics loloatins A-D (1-4),
      originally isolated from the marine bacterial isolate MK-PNG-276A, possibly in
      the genus Bacillus, was accomplished by solid-phase peptide synthesis (SPPS),
      followed by 'head-to-tail' cyclization of the activated linear precursors,
      without protection of nucleophilic side-chain functions, on a safety-catch resin.
      The synthetic peptides were equally active as the natural products isolated from
      the bacterial source and found to possess similar bacterial selectivity as other
      members in the family of amphipathic antimicrobial cyclic decapeptides.

PMID- 18081094
TI  - Studies on the cytotoxicity of miscellaneous compounds from Eupatorium
      betonicaeforme (D.C.) Baker (Asteraceae).
AB  - A detailed study on the cytotoxic effects of five known constituents isolated
      from the flowers and roots of Eupatorium betonicaeforme is reported, including
      2,2-dimethyl-6-vinylchroman-4-one (1), 2-senecioyl-4-vinylphenol (2), 6-acetyl
      2,2-dimethylchroman-4-one (3), (4E)-8beta-angeloyloxy-9beta,10beta-dihydroxy-1
      oxogermacra-4,11(13)-dien-12,6alpha-olide (4), and 3beta-hydroxyicosan-1,5beta
      olide (5). The sesquiterpene lactone 4 exhibited the highest cytotoxicity, with
      IC50 values ranging from 3.9 to 9.9 microM, showing some degree of cell
      selectivity. The antiproliferative activity of 4 was examined towards HL-60
      cells, and found to diminish cell viability in a dose-dependent manner. Moreover,
      at all concentrations tested, there was a decrease in the number of cells capable
      of incorporating 5-bromo-2'-deoxyuridine (BrdU), indicating disruption of DNA
      synthesis. The morphological changes induced by 4 were compatible with apoptotic
      cell death. This work, thus, corroborates the anticancer potential of Eupatorium
      secondary metabolites.

PMID- 18081095
TI  - Arguside A: a new cytotoxic triterpene glycoside from the sea cucumber Bohadschia
      argus Jaeger.
AB  - A new holostane-based triterpene glycoside, arguside A (1), was isolated from the
      sea cucumber Bohadschia argus, collected in the South China Sea. The structure of
      the new compound was elucidated by spectroscopic and mass-spectrometric analyses,
      in combination with chemical transformations. Compound 1 exhibited significant
      cytotoxicity against different human tumor cell lines, being more active towards
      HCT-116 cells (IC50 = 0.14 microM) than 10-hydroxycamptothecin (HCP) used as
      positive control.

PMID- 18081096
TI  - Glucosides from the roots of Capparis tenera.
AB  - Two new lignan glucosides, compounds 2 and 3, two new 1H-indole-alkaloid
      glucosides, 5 and 6, as well as two new phenolic glucosides, 7 and 10, were
      isolated from the roots of Capparis tenera, together with five known compounds.
      Their structures were characterized by chemical and spectroscopic methods. Most
      of these isolates were obtained for the first time from Capparidaceae. The
      antioxidant and anti-inflammatory activities of the new compounds were
      investigated.

PMID- 18081097
TI  - Effect of substitution pattern of ancillary ligands on the DNA-binding behavior
      of two new Ru(II)-polypyridyl complexes.
AB  - The new ligand 2-(4-phenoxyphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (ppip)
      and its Ru(II) complexes [Ru(2,9-dmp)2(ppip)]2+ (1) and [Ru(4,7-dmp)2(ppip)]2+
      (2; 2,9- and 4,7-dmp = 2,9- and 4,7-dimethyl-1,10-phenanthroline, resp.) were
      synthesized and characterized. The binding properties of the two complexes
      towards calf-thymus DNA (CT-DNA) in buffered H2O (pH 7.2) were investigated by
      different spectrophotometric methods and viscosity measurements. Both 1 and 2
      strongly bind to CT-DNA by means of intercalation, but with different binding
      strengths. In contrast to the more tightly bound complex 2, the sterically more
      demanding complex 1 showed no fluorescence emission, neither alone nor in the
      presence of CT-DNA. Our results demonstrate that the position of Me groups on
      phenanthroline (phen) ancillary ligands significantly affects the overall DNA
      recognition propensities of Ru(II)-polypyridyl complexes. Further, the partly
      resolved complex 2 was shown by circular dichroism (CD) to stereoselectively
      recognize CT-DNA, in contrast to 1.

PMID- 18081098
TI  - High diversity of Ligularia dictyoneura in chemical composition and DNA sequence.
AB  - The chemical composition of root extracts of the title species collected at 20
      different places in the Hengduan Mountains of China was examined. From these
      samples, a total of 17 eremophilane derivatives were isolated, three of which
      were new franoeremophilane derivatives: 3beta-acetoxy-6beta
      (angeloyloxy)furanoeremophilan-10beta-ol, 1alpha-acetoxyfuranoeremophilan
      15,6alpha-olide, and 6beta-[2-(hydroxymethyl)prop-2-enoyloxy]furanoeremophil
      1(10)-ene. Based on the chemical composition, the samples could be classified
      into as many as seven types: one type containing non-furanoeremophilane
      derivatives and the other six containing furanoeremophilane derivatives with
      different oxidation levels. Results of DNA sequencing of the atpB-rbcL region and
      the internal transcribed spacers of the ribosomal RNA gene also indicated a high
      diversity in the species.

PMID- 18081099
TI  - The first steps of chemical evolution towards the origin of life.

PMID- 18081100
TI  - Redox processes of sulfur and manganese in a constructed wetland.
AB  - Constructed wetlands are very popular in terms of wastewater treatment today.
      Formation of redox potential gradients inside such a system strongly influences
      the wastewater-treatment efficiency. Individual oxidation forms of sulfur, and
      dissolved and precipitated manganese forms were determined in the vegetation bed
      of the constructed wetland. The aim of the speciation analysis was to contribute
      to the characterization of its redox properties. Sulfur was mostly oxidized at
      the inflow. The concentration of sulfates at the inflow varied from 25 to 55
      mg/l, while concentration of sulfides was always lower than 6.0 mg/l and mostly
      even lower than 1.0 mg/l. However, sulfates were reduced during the pretreatment
      and the wastewater flow through the vegetation bed. The concentration of total
      manganese varied from 0.2 to 0.8 mg/l. Approximately 60% of Mn was precipitated
      at the inflow. The content of precipitated Mn forms declined to ca. 40-50% at the
      inflow zone, this content was almost constant across the vegetation bed to the
      outflow when water was sampled from 60-cm depth. However, the content of
      precipitated Mn forms increased to ca. 74% for samples from 20-cm depth. With
      respect to the aeration of the system, manganese can be precipitated as MnO2 in
      these samples.

PMID- 18081101
TI  - Three novel, structurally unique spirocyclic alkaloids from the halotolerant B-17
      fungal strain of Aspergillus variecolor.
AB  - During our search for novel antitumor lead compounds from microorganisms living
      under extreme conditions, three novel alkaloids, variecolortides A-C (1-3), were
      isolated from the mycelia of the halotolerant fungal strain Aspergillus
      variecolor B-17. The new compounds were found to share an unprecedented 'spiro
      anthronopyranoid diketopiperazine' structure, with a stable hemiaminal function,
      as corroborated by in-depth NMR-spectroscopic and mass-spectrometric analyses, as
      well as by a single-crystal X-ray analysis of 1. All compounds were shown to
      exhibit weak cytotoxic and antioxidant activities.

PMID- 18081103
TI  - Tetralones and flavonoids from Pyrola calliantha.
AB  - Two new tetralones, pyrolones A (1) and B (2), and a new flavonol glycoside, 2''
      O-(4-hydroxybenzoyl)hyperin (3), were isolated from Pyrola calliantha (whole
      plant), together with six structurally related compounds, including 2''-O
      galloylhyperin (4), hyperin (5), formononetin (6), quercetin 3-O-alpha-L
      arabinopyranoside (7), quercetin 3-O-alpha-L-arabinofuranoside (8), and
      kaempferol 3-O-beta-D-galactopyranoside (9). The structures and absolute
      configurations of the new compounds were elucidated on the basis of spectroscopic
      (UV, ORD, CD, NMR) and mass-spectrometric (HR-ESI-MS) analyses.

PMID- 18081104
TI  - Intra- and intermolecular interactions influence the reactivity of RNA
      oligonucleotides.
AB  - The transesterification of RNA oligonucleotides was studied over a wide pH range.
      The rate constants obtained indicate that, under neutral conditions,
      oligonucleotides with an adenosine moiety as the 5'-linked nucleoside can be up
      to 1000-fold more reactive than the reference oligonucleotide, a 13-mer oligo-U
      (1). Experiments with the modified oligonucleotide with N6,N6-dimethyladenosine
      (9) as the 5'-linked nucleoside moiety suggest that the exocyclic amino group is
      involved in the reaction, influencing the reactivity of the neighboring
      phosphodiester bond. In addition to such intramolecular interactions, weak
      intermolecular interactions most probably contribute to the reactivity.

PMID- 18081102
TI  - 4'''-Acetylvitexin-2''-O-rhamnoside, isoorientin, orientin, and 8
      methoxykaempferol-3-O-glucoside as markers for the differentiation of Crataegus
      monogyna and Crataegus pentagyna from Crataegus laevigata (Rosaceae).
AB  - In our chemotaxonomic investigation of pharmaceutically relevant Crataegus
      species, the qualitative and quantitative flavonoid fingerprint of Crataegus
      monogyna and C. pentagyna is presented. Six flavonoids were identified as vitexin
      2''-O-rhamnoside (1), vitexin (2), isovitexin (3), rutin (4), hyperoside (5), and
      isoquercitrin (6). Besides the verification of the main compounds isoorientin (7)
      and orientin (8) in C. pentagyna, further four flavonoids were isolated and
      identified as isoorientin-2''-O-rhamnoside (9), orientin-2''-O-rhamnoside (10),
      isovitexin-2''-O-rhamnoside (11), and 8-methoxykaempferol-3-O-glucoside (12) by
      means of 1D- and 2D-NMR, MS, and UV analyses. Compound 12 was isolated for the
      first time from C. pentagyna. In contrast to C. pentagyna, C. monogyna samples
      were predominated by 4'''-acetylvitexin-2''-O-rhamnoside (13), which was missing
      in C. pentagyna. Hence, 13 represents an interesting compound for chemotaxonomy
      of C. monogyna, whereas the main flavonoids 7, 8, and 12 could be proposed as
      markers for C. pentagyna. The absence of 7, 8, 12, and 13 in C. laevigata offers
      an appropriate tool for additional differentiation from C. monogyna and C.
      pentagyna, and for sample identification and quality control of the three main
      Crataegus species used in European phytotherapy.

PMID- 18081105
TI  - Two new alkaloids from Brachystemma calycinum and their inhibitory effects on
      lymphocyte proliferation.
AB  - Two new alkaloids, brachystemidines F (1) and G (2), were isolated from the roots
      of Brachystemma calycinum. Their structures were established on the basis of
      detailed spectroscopic analyses, including extensive NMR and HR-MS techniques.
      Compound 2, which exhibits an unusual N-hydroxydiazenyl (HO-N=N) moiety, is a
      potent immunosuppressive agent, as demonstrated by inhibition of mouse T- and B
      lymphocyte proliferation, with IC50 values of 6.33 and 5.60 microg/ml, resp.

PMID- 18081108
TI  - Structural investigation of endomorphins by experimental and theoretical methods:
      hunting for the bioactive conformation.

PMID- 18081109
TI  - The Center for the Study of Biological Complexity--the first five years.

PMID- 18081110
TI  - Enantioselective C--C bond formation to sulfonylimines through use of the 2
      pyridinesulfonyl group as a novel stereocontroller.
AB  - Enantioselective C--C bond formation to 2-pyridinesulfonylimines afforded
      products with good enantioselectivity. Dynamic induction of chirality on the
      sulfur by coordination of a chiral Lewis acid to the pyridine nitrogen and one of
      the prochiral sulfonyl oxygens induces enantioselectivity. Since the 2
      pyridinesulfonyl group can easily be removed after the reaction, it acts not only
      as an activating group but also as an efficient stereocontroller.

PMID- 18081111
TI  - More than bystanders: the effect of olefins on transition-metal-catalyzed cross
      coupling reactions.
AB  - Olefins and alkynes are ubiquitous in transition-metal catalysis, whether
      introduced by the substrate, the catalyst, or as an additive. Whereas the impact
      of metals and ligands is relatively well understood, the effects of olefins in
      these reactions are generally underappreciated, even though numerous examples of
      olefins influencing the outcome of a reaction, through increased activity,
      stability, or selectivity, have been reported. This Review provides an overview
      of the interaction of olefins with transition metals and documents examples of
      olefins influencing the outcome of catalytic reactions, in particular cross
      coupling reactions. It should thus provide a basis for the improved understanding
      and further utilization of olefin and alkyne effects in transition-metal
      catalyzed reactions.

PMID- 18081112
TI  - Diamonds are a chemist's best friend: diamondoid chemistry beyond adamantane.
AB  - Marilyn Monroe knew that "diamonds are a girl's best friend" but, in the
      meantime, many chemists have realized that they are also extremely attractive
      objects in contemporary chemistry. The chemist's diamonds are usually quite small
      (herein: nanometer-sized "diamondoids") and as a result of their unique structure
      are unusual chemical building blocks. Since lower diamondoids (up to triamantane)
      have recently become available in large amounts from petroleum and higher
      diamondoids (starting from tetramantane) are now also accessible from crude oil
      new research involving them has begun to emerge. Having well-defined structures
      makes these cage compounds so special compared to other nanometer-scale diamonds.
      Selective and high-yielding synthetic approaches to the functionalization of
      diamondoids gives derivatives that can find applications in, for example,
      polymers, coating materials, drugs, and molecular electronics.

PMID- 18081113
TI  - Supramolecular assemblies based on organometallic quinonoid linkers: a new class
      of coordination networks.
AB  - Self-assembly of coordination frameworks exhibiting original architectures is an
      active area of research. Generally, such assemblies are constructed from organic
      spacers and transition metals of different geometrical structures. Herein, we
      report a novel class of supramolecular coordination assemblies with
      organometallic linkers based on metalated quinonoid and thioquinonoid complexes
      that serve as spacers. The organometallic ligands are stable and have the general
      formula [Cp*M(eta(4)-benzoquinone)] (o- and p-benzoquinone, Cp*=C(5)Me(5), M=Rh,
      Ir) and [Cp*Ir(eta(4)-thiobenzoquinone)] (o- and p-thiobenzoquinone). These units
      bind through both oxygen or sulfur atoms to metal ions of different coordination
      geometry, such as Cu(I), Ag(I), and Pt(II), to generate supramolecular
      coordination networks, with the metalated quinonoid or thioquinonoid linkers
      acting as backbones and the metal centers as nodes. This novel family of
      supramolecular assemblies exhibits short pi-pi and MM interactions. These results
      illustrate successfully the role of the organometallic linkers to produce an
      impressive range of novel supramolecular architectures that hold promise for the
      development of functional materials.

PMID- 18081114
TI  - Cascade reactions using LiAlH4 and grignard reagents in the presence of water.

PMID- 18081115
TI  - A new design strategy for organic optoelectronic materials by lateral boryl
      substitution.

PMID- 18081116
TI  - Palladium-catalyzed aryl amination-heck cyclization cascade: a one-flask approach
      to 3-substituted indoles.

PMID- 18081117
TI  - Golden carousel in catalysis: the cationic gold/propargylic ester cycle.

PMID- 18081118
TI  - Self-flocculating/self-dispersing oscillation of microgels.

PMID- 18081119
TI  - Octa-, deca-, trideca-, and tetradecanuclear heterometallic cyclic chromium
      copper cages.

PMID- 18081120
TI  - Intramolecular carbolithiation of alkynes: anti selectivity.

PMID- 18081121
TI  - Cyclic triolborates: air- and water-stable ate complexes of organoboronic acids.

PMID- 18081122
TI  - Foam films obtained with ionic liquid.

PMID- 18081123
TI  - Platinum-catalyzed intramolecular [4C+3C] cycloaddition between dienes and
      allenes.

PMID- 18081124
TI  - Catalytic asymmetric reaction with water: enantioselective synthesis of alpha
      hydroxyesters by a copper-carbenoid O-H insertion reaction.

PMID- 18081125
TI  - Decrypting the TEM images for deciphering the microstructural code of complex
      oxides.
AB  - The knowledge of the structure of the real solids is required for achieving the
      desired architectures in the research of new materials and/or optimizing the
      relationships between structure and properties. Understanding complex oxides
      needs accurate characterization at different length scales and the combined
      application of all solid-state techniques. Deciphering the relationships between
      all this information provides codes that allow the identification of the
      different structural levels, their roles and the way they interact. These step-by
      step routes are illustrated through two basic mechanisms of solid-state
      chemistry: to determine the building units of one complex oxide in order to
      predict the existence of other arrangements on the one hand and to correlate
      complex ordering phenomena, such as those involving charges, orbitals and spins
      of manganese atoms in perovskite-type manganites on the other hand.

PMID- 18081126
TI  - New chiral lanthanide amide ate complexes for the catalysed synthesis of scalemic
      nitrogen-containing heterocycles.
AB  - New chiral binaphthylamido yttrium and ytterbium ate complexes with lithium and
      potassium counterions have been synthesised and characterised. X-ray structures
      have been obtained for [Li(thf)4][Ln{(R)-C20H12(NC5H9)2}2] (Ln=Yb, Y) and
      [K(thf)5][Yb{(R)-C20H12(NCH2CMe3)2}2] as isostructural complexes. The efficiency
      of these complexes for the enantioselective intramolecular hydroamination was
      examined. [Li(thf)4][Yb{(R)-C20H12(NC5H9)2}2] afforded the highest enantiomeric
      excess (up to 87 %) for the synthesis of a spiropyrrolidine, while
      [Li(thf)4][Y{(R)-C20H12(NC5H9)2}2] proved to be slightly more active. The role of
      the counter cation in the active catalytic species was evidenced by the
      comparison between lithium and potassium ate complexes. The most active catalyst
      of this series, [Li(thf)4][Yb{(R)-C20H12(NCH2CMe3)2}2], was successfully used for
      the cyclisation of aminopentenes with internal double bonds.

PMID- 18081127
TI  - Half-sandwich o-N,N-dimethylaminobenzyl complexes over the full size range of
      group 3 and lanthanide metals. synthesis, structural characterization, and
      catalysis of phosphine P--H bond addition to carbodiimides.
AB  - The acid-base reactions between the rare-earth metal (Ln) tris(ortho-N,N
      dimethylaminobenzyl) complexes [Ln(CH2C(H4NMe2-o)3] with one equivalent of the
      silylene-linked cyclopentadiene-amine ligand (C5Me4H)SiMe2NH(C6H2Me3-2,4,6)
      afforded the corresponding half-sandwich aminobenzyl complexes
      [{Me2Si(C5Me4)(NC6H2Me3-2,4,6)}Ln(CH2C6H4NMe2-o)(thf)] (2-Ln) (Ln=Y, La, Pr, Nd,
      Sm, Gd, Lu) in 60-87 % isolated yields. The one-pot reaction between ScCl(3) and
      [Me2Si(C5Me4)(NC6H2Me3-2,4,6)]Li2 followed by reaction with LiCH2C6H4NMe2-o in
      THF gave the scandium analogue [{Me2Si(C5Me4)(NC6H2Me3-2,4,6)}Sc(CH2C6H4NMe2-o)]
      (2-Sc) in 67 % isolated yield. 2-Sc could not be prepared by the acid-base
      reaction between [Sc(CH2C6H4NMe2-o)3] and (C5Me4H)SiMe2NH(C6H2Me3-2,4,6). These
      half-sandwich rare-earth metal aminobenzyl complexes can serve as efficient
      catalyst precursors for the catalytic addition of various phosphine P--H bonds to
      carbodiimides to form a series of phosphaguanidine derivatives with excellent
      tolerability to aromatic carbon-halogen bonds. A significant increase in the
      catalytic activity was observed, as a result of an increase in the metal size
      with a general trend of La>Pr, Nd>Sm>Gd>Lu>Sc. The reaction of 2-La with 1 equiv
      of Ph2PH yielded the corresponding phosphide complex [{Me2Si(C5Me4)(NC6H2Me3
      2,4,6)}La(PPh2)(thf)2] (4), which, on recrystallization from benzene, gave the
      dimeric analogue [{Me2Si(C5Me4)(NC6H2Me3-2,4,6)}La(PPh2)]2 (5). Addition of 4 or
      5 to iPrN=C=NiPr in THF yielded the phosphaguanidinate complex
      [{Me2Si(C5Me4)(NC6H2Me3-2,4,6)}La{iPrNC(PPh2)NiPr}(thf)] (6), which, on
      recrystallization from ether, afforded the ether-coordinated structurally
      characterizable analogue [{Me2Si(C5Me4)(NC6H2Me3
      2,4,6)}La{iPrNC(PPh2)NiPr}(OEt2)] (7). The reaction of 6 or 7 with Ph2PH in THF
      yielded 4 and the phosphaguanidine iPrN=C(PPh2)NHiPr (3a). These results suggest
      that the catalytic formation of a phosphaguanidine compound proceeds through the
      nucleophilic addition of a phosphide species, which is formed by the acid-base
      reaction between a rare-earth metal o-dimethylaminobenzyl bond and a phosphine P-
      H bond, to a carbodiimide, followed by the protonolysis of the resultant
      phosphaguanidinate species by a phosphine P--H bond. Almost all of the rare earth
      complexes reported this paper were structurally characterized by X-ray
      diffraction studies.

PMID- 18081128
TI  - Antiaromaticity and reactivity of a planar cyclooctatetraene fully annelated with
      bicyclo[2.1.1]hexane units.
AB  - A detailed investigation has been made into the antiaromaticity and chemical
      reactivity of a planar cyclooctatetraene (COT) molecule fully annelated with
      bicyclo[2.1.1]hexane units 2. In spite of its planar 8pi-electronic structure,
      theoretical calculations have indicated that the antiaromaticity of COT 2 is
      considerably decreased in comparison with a planar COT 16 with D 4h symmetry.
      This behavior appears to be related to the wider HOMO-LUMO gap of 2 relative to
      16, which is caused by the raised LUMO level as a result of the effective sigma
      pi* orbital interaction between the strained bicyclic framework and the COT pi
      system. The two-electron reduction of 2 required the use of potassium mirror or a
      combination of lithium/corannulene in highly dried [D8]THF at -78 degrees C under
      vacuum. In contrast, the [4+2] cycloaddition of 2 with tetracyanoethylene (TCNE)
      proceeded quite smoothly owing to the high-lying HOMO. Reaction of 2 with meta
      chloroperbenzoic acid gave all-trans tetraepoxide 23 in the same way as the
      corresponding benzene derivative 3. While the Simons-Smith-type cyclopropanation
      of benzene 3 gave tricyclopropanated derivative 21, the reaction of 2 only
      afforded isomers of dicyclopropanated derivatives 25 and 26. Yet, the reactivity
      of 2 is higher than the parent COT, which does not show any reactivity under the
      same conditions. On the basis of homodesmic reactions, it was concluded that
      release of strain is also an important factor for such relatively high reactivity
      in the epoxidation and cyclopropanation of bicycloannelated COT 2 as well as
      benzene 3.

PMID- 18081129
TI  - Exploring the relation between amplification and binding in dynamic combinatorial
      libraries of macrocyclic synthetic receptors in water.
AB  - Herein we describe an extensive study of the response of a set of closely related
      dynamic combinatorial libraries (DCLs) of macrocyclic receptors to the
      introduction of a focused range of guest molecules. We have determined the
      amplification of two sets of diastereomeric receptors induced by a series of
      neutral and cationic guests, including biologically relevant compounds such as
      acetylcholine and morphine. The host-guest binding affinities were investigated
      using isothermal titration calorimetry. The resulting dataset enabled a detailed
      analysis of the relationship between the amplification of selected receptors and
      host-guest Gibbs binding energies, giving insight into the factors affecting the
      design, simulation and interpretation of DCL experiments. In particular, two
      questions were addressed: Is amplification by a given guest selective for the
      best receptor? And does the best guest induce the largest amplification of a
      given receptor? Our experimental results and computer simulations showed that the
      relative levels of amplification of hosts by a guest are well-correlated with
      their relative affinities, and simulations have confirmed previous observations
      that amplification can be selective for the best receptor when only modest
      amounts of guest are used. In contrast, the correlation between guest binding and
      the extent of amplification of a given receptor across a wide range of guests
      tends to be poorer, because every guest has its own unique set of affinities for
      competing receptors in the DCL. This implies that the results of screening a DCL
      for selective receptors by comparing the response of the mixture to two different
      guests should be interpreted with caution. DCLs are complex mixtures in which all
      compounds are connected through a set of equilibria. Obtaining quantitative
      information about all host-guest binding constants from such systems will require
      the explicit and simultaneous consideration of all of the main equilibria within
      a DCL.

PMID- 18081130
TI  - Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and
      gene expression in mammalian cells.
AB  - Through the use of various layer-by-layer polyelectrolyte (PE) coating schemes,
      such as the common poly(diallyldimethylammonium chloride)-poly(4-styrenesulfonic
      acid) (PDADMAC-PSS) system, the mammalian cellular uptake of gold nanorods can be
      tuned from very high to very low by manipulating the surface charge and
      functional groups of the PEs. The toxicity of these nanorods is also examined.
      Since the PE coatings are individually toxic, the toxicity of nanorods coated in
      these PEs is measured and cells are found to be greater than 90% viable in nearly
      all cases, even at very high concentrations. This viability assay may not be a
      complete indicator of toxicity, and thus gene-expression analysis is used to
      examine the molecular changes of cells exposed to PDADMAC-coated nanorods, which
      enter cells at the highest concentrations. Indicators of cell stress, such as
      heat-shock proteins, are not significantly up- or down-regulated following
      nanorod uptake, which suggests that PDADMAC-coated gold nanorods have negligible
      impact on cell function. Furthermore, a very low number of genes experience any
      significant change in expression (0.35% of genes examined). These results
      indicate that gold nanorods are well suited for therapeutic applications, such as
      thermal cancer therapy, due to their tunable cell uptake and low toxicity.

PMID- 18081131
TI  - Quantum-dot-based electrochemical immunoassay for high-throughput screening of
      the prostate-specific antigen.

PMID- 18081132
TI  - Ultrasharp optical-fiber nanoprobe array for Raman local-enhancement imaging.

PMID- 18081133
TI  - A multidisciplinary approach for the identification of novel HIV-1 non-nucleoside
      reverse transcriptase inhibitors: S-DABOCs and DAVPs.
AB  - Among the FDA approved drugs for the treatment of AIDS, non-nucleoside reverse
      transcriptase inhibitors (NNRTIs) are essential components of first-line anti-HIV
      1 therapy because of the less-severe adverse effects associated with NNRTIs
      administration in comparison to therapies based on other anti-HIV-1 agents. In
      this contest, 3,4-dihydro-2-alkoxy-6-benzyl-4-oxypyrimidines (DABOs) have been
      the object of many studies aimed at identifying novel analogues endowed with
      potent inhibitory activity towards HIV-1 wild type and especially drug-resistant
      mutants. Accordingly, based on the encouraging results obtained from the
      biological screening of our internal collection of S-DABO derivatives, we started
      with the systematic functionalization of the pyrimidine scaffold to identify the
      minimal required structural features for RT inhibition. Herein, we describe how
      the combination of synthetic, biological, and molecular modeling studies led to
      the identification of two novel subclasses of S-DABO analogues: S-DABO cytosine
      analogues (S-DABOCs) and 4-dimethyamino-6-vinylpyrimidines (DAVPs).

PMID- 18081134
TI  - Modeling and selection of flexible proteins for structure-based drug design:
      backbone and side chain movements in p38 MAPK.
AB  - Receptor rearrangement upon ligand binding (induced fit) is a major stumbling
      block in docking and virtual screening. Even though numerous studies have
      stressed the importance of including protein flexibility in ligand docking,
      currently available methods provide only a partial solution to the problem. Most
      of these methods, being computer intensive, are often impractical to use in
      actual drug discovery settings. We had earlier shown that ligand-induced receptor
      side-chain conformational changes could be modeled statistically using data on
      known receptor-ligand complexes. In this paper, we show that a similar approach
      can be used to model more complex changes like backbone flips and loop movements.
      We have used p38 MAPK as a test case and have shown that a few simple structural
      features of ligands are sufficient to predict the induced variation in receptor
      conformations. Rigorous validation, both by internal resampling methods and on an
      external test set, corroborates this finding and demonstrates the robustness of
      the models. We have also compared our results with those from an earlier
      molecular dynamics simulation study on DFG loop conformations of p38 MAPK, and
      found that the results matched in the two cases. Our statistical approach enables
      one to predict the final ligand-induced conformation of the active site of a
      protein, based on a few ligand properties, prior to docking the ligand. We can do
      this without having to trace the step-by-step process by which this state is
      arrived at (as in molecular dynamics simulations), thereby drastically reducing
      computational effort.

PMID- 18081135
TI  - Mg 2+-doped GaN nanoparticles as blue-light emitters: a method to avoid sintering
      at high temperatures.
AB  - Bright blue-light emission at 410 nm is observed from Mg(2+)-doped GaN
      nanoparticles prepared by the nitridation of Ga(2)MgO(4) nanoparticles at 950
      degrees C. The sintering of these nanoparticles during high-temperature
      nitridation was prevented by mixing the Ga(2)MgO(4) precursor nanoparticles with
      La(2)O(3) as an inert matrix before the nitridation process. The Mg(2+)-doped GaN
      nanoparticles were isolated from the matrix by etching with 10 % nitric acid. The
      Mg(2+)-doped GaN nanoparticles were characterized by photoluminescence, atomic
      force microscopy, X-ray diffraction, and IR analyses.

PMID- 18081141
TI  - Infrared measurement of human skin temperature to predict the individual maximum
      safe radiant exposure (IMSRE).
AB  - BACKGROUND AND OBJECTIVES: Radiant exposure (RE) is a critical treatment
      parameter to be optimized for laser hair removal (LHR). An objective and
      quantitative method to assess the individual maximum safe radiant exposure
      (IMSRE) would help clinicians optimize LHR while at the same time providing the
      safest possible laser therapy. STUDY DESIGN: Pulsed photo-thermal radiometry
      (PPTR) measurements were on a total of 403 spots on 13 volunteers. The
      radiometric signal at 20 milliseconds after the diagnostic laser pulse was used
      to predict the IMSRE using a simple analytic relationship. Laser pulses
      (wavelength 755 nm, 3 milliseconds pulse, 50 milliseconds cryogen spray cooling,
      30 milliseconds delay) with RE's below and above the predicted IMSRE (range: 10
      100 J/cm(2)) were applied and resulting injuries quantified through blind
      scoring. RESULTS: IMSRE can be predicted quite robustly with PPTR for the broad
      range of human skin photo-types (I-IV) considered in this study. CONCLUSIONS: The
      method presented herein should be useful in helping clinicians optimize LHR on an
      individual patient basis, with the highest possible safety.

PMID- 18081142
TI  - Effect of low-level laser therapy on bone repair: histological study in rats.
AB  - BACKGROUND AND OBJECTIVES: Bone remodeling is characterized as a cyclic and
      lengthy process. It is currently accepted that not only this dynamics is
      triggered by a biological process, but also biochemical, electrical, and
      mechanical stimuli are key factors for the maintenance of bone tissue. The
      hypothesis that low-level laser therapy (LLLT) may favor bone repair has been
      suggested. The purpose of this study was to evaluate the bone repair in defects
      created in rat lower jaws after stimulation with infrared LLLT directly on the
      injured tissue. STUDY DESIGN/MATERIALS AND METHODS: Bone defects were prepared on
      the mandibles of 30 Holtzman rats allocated in two groups (n = 15), which were
      divided in three evaluation period (15, 45, and 60 days), with five animals each.
      control group-no treatment of the defect; laser group-single laser irradiation
      with a GaAlAs semiconductor diode laser device (lambda = 780 nm; P = 35 mW; t =
      40 s; Theta = 1.0 mm; D = 178 J/cm(2); E = 1.4 J) directly on the defect area.
      The rats were sacrificed at the pre-established periods and the mandibles were
      removed and processed for staining with hematoxylin and eosin, Masson's Trichrome
      and picrosirius techniques. RESULTS: The histological results showed bone
      formation in both groups. However, the laser group exhibited an advanced tissue
      response compared to the control group, abbreviating the initial inflammatory
      reaction and promoting rapid new bone matrix formation at 15 and 45 days
      (P<0.05). On the other hand, there were no significant differences between the
      groups at 60 days. CONCLUSION: The use of infrared LLLT directly to the injured
      tissue showed a biostimulating effect on bone remodeling by stimulating the
      modulation of the initial inflammatory response and anticipating the resolution
      to normal conditions at the earlier periods. However, there were no differences
      between the groups at 60 days.

PMID- 18081143
TI  - GaAlAs (830 nm) low-level laser enhances peripheral endogenous opioid analgesia
      in rats.
AB  - BACKGROUND: Low-level laser therapy (LLLT) has been reported to relieve pain with
      minimal side effects. Recent studies have demonstrated that opioid-containing
      immune cells migrate to inflamed sites and release beta-endorphins to inhibit
      pain as a mode of peripheral endogenous opioid analgesia. The present study
      investigates whether LLLT may enhance peripheral endogenous opioid analgesia.
      METHODS: The effect of LLLT on opioid analgesia and production was evaluated in
      vivo in a rat model of inflammation as well as in vitro in Jurkat cells, a human
      T-cell leukemia cell line. mRNA expression of the beta-endorphin precursors
      proopiomelanocortin and corticotrophin releasing factor was assessed by reverse
      transcription polymerase chain reaction. RESULTS: LLLT produced an analgesic
      effect in inflamed peripheral tissue which was transiently antagonized by
      naloxone. Beta-endorphin precursor mRNA expression increased with LLLT, both in
      vivo and in vitro. CONCLUSION: This study demonstrates that LLLT produces
      analgesic effects in a rat model of peripheral inflammation. We further revealed
      an additional mechanism of LLLT-mediated analgesia via enhancement of peripheral
      endogenous opioids. These findings suggest that LLLT induces analgesia in rats by
      enhancing peripheral endogenous opioid production in addition to previously
      reported mechanisms.

PMID- 18081144
TI  - KTP laser and nitinol alloy stents: are they compatible?
AB  - BACKGROUND/OBJECTIVE: Nitinol alloy stents are in frequent use in recanalizing
      malignant airway stenoses. Potassium titanyl phosphate (KTP) is one of the lasers
      of choice in removal of obstructing airway lesions. There is a paucity of
      research regarding the safety of these advances working together. STUDY
      DESIGN/MATERIALS AND METHODS: In vitro study involving direct contact application
      of KTP laser with nitinol alloy stents under microscope guidance in varying
      gaseous environments. RESULTS: Stent damage can occur once power settings exceed
      one watt. Complete stent destruction occurs regardless of gaseous environment at
      a mere three watts of power. CONCLUSIONS: Our results suggest that KTP laser is
      unsafe to use in the presence of a nitinol alloy stent, regardless of the gaseous
      environment.

PMID- 18081147
TI  - A randomised, split-face comparison of facial hair removal with the alexandrite
      laser and intense pulsed light system.
AB  - INTRODUCTION: Despite the high incidence of polycystic ovary syndrome (PCOS) in
      women attending for facial hair removal there are few studies looking
      specifically at this patient group. We carried out a split-face study directly
      comparing the efficacy of a 3 milliseconds pulse duration alexandrite laser with
      the Lumina IPL system in 38 women with PCOS. MATERIALS AND METHODS: Each patient
      underwent six treatments using both systems, with 1, 3 and 6 months follow-up.
      Hair counts, hair-free intervals and patient satisfaction were recorded for all
      patients. RESULTS: After six treatments, alexandrite laser treatment resulted in
      longer median hair-free intervals when compared to IPL (7 weeks vs. 2 weeks; P <
      0.001). Decrease in hair counts was significantly larger on the Alexandrite side
      compared to the IPL side at 1, 3 and 6 months (52%, 43% and 46% vs. 21%, 21% and
      27%; P < 0.001). Patient satisfaction scores, using linear analogue scales (LAS),
      at 1, 3 and 6 months were significantly higher for the alexandrite laser than the
      IPL (8.7, 7.8 and 7.7 vs. 5.7, 5.1 and 5.1; P < or = 0.002). CONCLUSIONS: The
      alexandrite laser resulted in significantly longer hair-free intervals, a larger
      reduction in hair counts and greater patient satisfaction than the IPL and
      appeared to be more effective in this patient group. It is clear from the results
      in this study that the GentleLase alexandrite laser is more effective at reducing
      facial hirsutism in women with PCOS than the Lumina IPL. It is probable that this
      is due to the specific wavelength, short pulse duration and single pulse delivery
      of the GentleLase alexandrite laser, resulting in more follicular destruction
      than the IPL.

PMID- 18081148
TI  - Diode laser hair removal around ileo-colo ostomys is safe, effective and
      beneficial: a pilot study.
AB  - BACKGROUND AND OBJECTIVE: Hair removal around an ileo-colo ostomy can cause a
      number of problems. We compared laser hair removal with mechanical shaving around
      the ostomy. METHOD: Eleven patients were selected with hairy skin around the
      ostomy for therapy with an AlGaAs diode laser at 800 nm. Three to four treatments
      were given with an interval of 6 weeks. RESULTS: Ten patients completed laser
      therapy. The average hair reduction was 60% based on visual inspection. Shaving
      frequency reduced from once a week to once every 6 weeks. CONCLUSIONS: Laser hair
      removal likely becomes the preferred method in ostomy patients.

PMID- 18081149
TI  - A novel "patient-like" model of cholangiocarcinoma progression based on bile duct
      inoculation of tumorigenic rat cholangiocyte cell lines.
AB  - Intrahepatic cholangiocarcinoma typically presents in an advanced stage in which
      treatment options are limited. In an effort to recapitulate key biological and
      clinical features of the progressive disease, we established a novel rat model
      based on bile duct inoculation of rat cholangiocyte cell lines in different
      stages of tumor progression. Our BDEneu cell line, which is highly tumorigenic,
      originated from an immortalized rat cholangiocyte cell line (BDE1 cells) that was
      stably transfected to constitutively overexpress mutationally activated rat neu
      oncogene. Our less aggressive tumorigenic BDEsp cholangiocyte cell line was
      derived from the spontaneous in vitro neoplastic transformation of the same
      parent BDE1 cell line. Unlike BDEneu cells, BDEsp cells expressed wild-type c-neu
      and exhibited in vitro growth rates intermediate between those of BDEneu and BDE1
      cholangiocytes. Cyclooxygenase-2 and activated Akt were significantly
      overexpressed in BDEsp cells over those of BDE1 cells, and at higher levels than
      those expressed in BDEneu cells. Only BDEneu cells overexpressed activated
      p185(neu), which was associated with a significant increase in phospho-p44/42
      mitogen-activated protein kinase (MAPK). Mucin 1 (MUC1) messenger RNA (mRNA), an
      indicator of cholangiocarcinoma cell progression, was also significantly
      overexpressed in BDEneu cells over that of BDEsp cells. BDEneu cells inoculated
      into the bile duct of isogenic rats resulted over a 21- to 26-day period in rapid
      exponential cholangiocarcinoma tumor growth within liver, paralleled by increases
      in bile duct obstruction and gross peritoneal metastases. Under comparable
      conditions, BDEsp cells yielded only small nonmetastatic intrahepatic
      cholangiocarcinomas without bile duct obstruction. CONCLUSIONS: A novel model of
      cholangiocarcinoma progression mimicking progressive development of the advanced
      human disease has been established, which may serve as a powerful preclinical
      platform to study cholangiocarcinoma progression and for rapidly testing
      treatment approaches.

PMID- 18081150
TI  - The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular
      transformation and tumor formation without Ha-ras co-transfection.
AB  - Hepatitis C virus (HCV) is an important cause of chronic liver disease and is
      complicated by hepatocellular carcinoma (HCC). Mechanisms whereby the virus
      promotes cellular transformation are poorly understood. We hypothesized that the
      guanosine triphosphatase activity encoded in the HCV NS4B protein's nucleotide
      binding motif (NBM) might play a role in the transformation process. Here we
      report that NS4B can transform NIH-3T3 cells, leading to tumor formation in vivo.
      This transformation was independent of co-transfection with activated Ha-ras.
      Detailed analyses of NS4B mutants revealed that this transforming activity could
      be progressively inhibited and completely abrogated by increasing genetic
      impairment of the NS4B nucleotide binding motif. CONCLUSION: NS4B has in vitro
      and in vivo tumorigenic potential, and the NS4B transforming activity is indeed
      mediated by its NBM. Moreover, our results suggest that pharmacological
      inhibition of the latter might inhibit not only HCV replication but also the
      associated HCC.

PMID- 18081151
TI  - Impact of pre- and postoperative multimodality therapy on rectal cancer.
AB  - Surgery is the primary treatment of rectal cancer. However, variability in
      surgical outcomes led to development of combined therapies including pelvic
      radiation and systemic chemotherapy. The evolution of these therapies both
      individually and combined, their successes and limitations is discussed in the
      context of an evolving understanding of rectal cancer biology. The impact of
      standardized optimal surgery on the need for additional therapy and trends in
      treating complete responders to neoadjuvant therapy is also reviewed.

PMID- 18081152
TI  - The role of clinical trials in the development of novel surgical techniques.
AB  - The new paradigm and standard for medicine and surgery is the evidence-based
      practice for which the randomized controlled trial is fundamental. Despite the
      early involvement of surgeons in clinical trials, randomized trials testing novel
      surgical therapies are not common. Indeed, only 24% of surgical patients are
      managed based on level 1 evidence. This chapter details how randomized controlled
      trial methodologies facilitate the development of level 1 evidence in support of
      minimally invasive colon cancer surgery.

PMID- 18081153
TI  - Molecular profiling and risk stratification of adenocarcinoma of the colon.
AB  - Staging systems are used to predict the clinical and biologic behavior of tumors.
      This manuscript examines several molecular markers that hope to improve staging
      for colon cancer. It is unclear if a molecular marker, genetic signature, or a
      combination of histologic, genetic, and molecular parameters will provide the
      best prognostic information. What is clear is that more accurate staging tools
      are needed so patients receive the best therapy.

PMID- 18081154
TI  - Geriatric syndromes in elderly patients admitted to an inpatient cardiology ward.
AB  - BACKGROUND: Older adults make up an increasing proportion of patients
      hospitalized with cardiovascular disease. Such patients often have multiple
      coexisting geriatric syndromes that may affect management and outcomes and are
      frequently underdiagnosed and untreated. OBJECTIVES: To determine the prevalence
      of geriatric syndromes and incidence of selected adverse events in hospitalized
      elderly patients with cardiovascular disease. DESIGN: A prospective cohort study.
      SETTING: Urban academic medical center. PATIENTS: One hundred patients at least
      70 years old with cardiovascular disease hospitalized on a cardiology ward.
      MEASUREMENTS: Standard geriatric screens were administered to assess mood,
      function, and cognitive status. Patients were followed prospectively for adverse
      events such as falls, urinary tract infection (UTI), and use of restraints.
      RESULTS: The mean age of the patients was 79.2 +/- 5.5 years, 61% were female,
      68% were white, and mean length of stay was 7 days. Geriatric syndromes were
      prevalent and included functional impairment (35% dependent in >or=1 activity of
      daily living), cognitive impairment (19% with abnormal results on the Short
      Blessed Test), and polypharmacy. Thirty-seven percent of patients were prescribed
      a potentially inappropriate medication on admission or discharge. Patients
      receiving a Foley catheter were at increased risk for UTI. CONCLUSIONS: These
      findings suggest that geriatric syndromes are prevalent among older patients
      hospitalized for cardiovascular disease. Further study is needed to determine if
      interventions designed to increase recognition and treatment of these syndromes
      can improve outcomes in this patient population.

PMID- 18081155
TI  - No association of genetic variants of liver X receptor-beta with Alzheimer's
      disease risk.
AB  - Apolipoprotein E (APOE) epsilon4 allele is the strongest hitherto known risk
      factor for sporadic Alzheimer's disease (AD). Liver X receptor-beta (LXRbeta) is
      a transcription factor that controls expression of genes involved in brain
      cholesterol metabolism, and one of the main LXRbeta targets is APOE. To evaluate
      the relationship between LXRbeta genetic variants and AD, independently or in
      concert with the APOE epsilon4 allele, we examined three LXRbeta polymorphisms
      located in introns 2 (rs 2695121), 5 (rs 1052533), and 7 (rs 1405655), in 414
      Spanish AD patients and 447 controls. The current study does not demonstrate an
      association between LXRbeta genotypes or haplotypes and AD, neither in the total
      sample nor when the populations were stratified for the presence or absence of
      the APOE epsilon4 allele.

PMID- 18081157
TI  - Evidence for association between genetic variants of p75 neurotrophin receptor
      (p75NTR) gene and antidepressant treatment response in Chinese major depressive
      disorder.
AB  - The p75 neurotrophin receptor (p75(NTR)) is an essential component of
      neurotrophin system, and has been implicated in the pathogenesis of major
      depressive disorder (MDD) and in the mechanism of antidepressant action. This
      study aimed to delineate the association between phenotype (MDD susceptibility
      and antidepressant response) and genotype (p75(NTR) common genetic variants) in a
      Chinese population. A total of 228 MDD patients and 402 unrelated controls were
      recruited. Subjects took selective serotonin reuptake inhibitors (SSRIs) and
      responders were defined as those with at least a 50% decrease in score of the
      Hamilton Rating Scale for Depression (HAM-D) from baseline. Five p75(NTR)
      polymorphisms were genotyped and their association with MDD or treatment response
      was assessed by haplotype and single marker analysis. No significant association
      with MDD was discovered in single locus or haplotype analyses. With regard to the
      therapeutic outcome, however, one missense polymorphism (S250L) showed
      association in both genotype distribution (P = 0.039) and allele frequency (P =
      0.012). Haplotype analysis also revealed that p75(NTR) TCT carriers had a more
      unfavorable response to therapy (P = 0.010). Our exploratory study has
      demonstrated the association between p75(NTR) and SSRI response for the first
      time, which may assist in individualized therapy for MDD patients in the future.

PMID- 18081158
TI  - Suggestive linkage of a chromosomal locus on 18p11 to cyclothymic temperament in
      bipolar disorder families.
AB  - Attempts to identify bipolar disorder (BP) genes have only enjoyed limited
      success. One potential cause for this problem is that the traditional categorical
      BP phenotypes currently used in genetic linkage studies are not the most
      informative, efficient, or biologically relevant. An alternative to these strict
      categorical BP phenotypes is quantitative BP phenotypes. By isolating one aspect
      of a complex trait such as BP into a simple, intermediate, quantitative trait,
      genes that contribute to the larger complex trait can be more readily identified.
      Along these lines, we utilized a temperament-based measure (cyclothymic
      temperament) as a quantitative, intermediate BP phenotype in linkage analyses and
      hypothesized that this measure might more efficiently detect loci for BP or
      temperamental traits that predispose to BP. A total of 158 individuals with
      temperament data from 28 BP families were used in the linkage analyses. All
      pedigrees had a proband diagnosed with BPI or BPII and at least two other family
      members with a mood disorder diagnosis. An 8 cM genome scan was performed and
      analyzed using MERLIN nonparametric multipoint regression linkage for a
      cyclothymic temperament trait. The highest overall LOD score was on chromosome 18
      (LOD = 2.71, P = 0.0002). Other linkage peaks which may indicate potential
      regions of interest were found on chromosomes 3 and 7. The temperament-based
      cyclothymic trait yielded a higher peak LOD score and a lower P-value than
      analyses using traditional, categorical phenotypes in a separate analysis
      including these same families.

PMID- 18081160
TI  - Colon cancer: trials, results, techniques (LAP and HALS), future.
AB  - Laparoscopic resection of colon cancer became mired in controversy when it
      appeared that the technique might be associated with an increased risk of tumor
      recurrence within the surgical incisions. This was not a uniform finding among
      all surgeons, however, and other evidence suggested that this did not occur in
      experienced hands. Thus were born several randomized controlled trials of
      laparoscopic versus open colectomy for cancer in the early and mid-1990s. These
      trials came to maturity between 2002 and 2006 and form the basis of this review.

PMID- 18081161
TI  - Laparoscopic proctectomy for rectal adenocarcinoma.
AB  - During the past 15 years, there has been increasing enthusiasm for the use of
      laparoscopic techniques in the operative treatment of patients suffering from
      colorectal disease. Laparoscopic colectomy has been demonstrated to be safe for
      patients suffering from adenocarcinoma of the intraperitoneal colon. Attention is
      now being focused on the treatment of patients with rectal adenocarcinoma using
      laparoscopic methods. Prospective data analysis will be crucial in determining
      whether laparoscopic proctectomy provides equivalent results to open procedures.

PMID- 18081162
TI  - Clinical significance of RLS.
AB  - While the restless legs syndrome (RLS) may have been known in antiquity, it has
      only recently come to medical attention. Individuals with RLS fall along a
      spectrum from mild, infrequent symptoms to those with severe daily life-impairing
      discomforts and sleep disruption. These problems can cause impaired mood, daytime
      fatigue, cognitive difficulties, and inability to participate in a variety of
      quiet activities. This leads to a general reduction in quality of life similar to
      other significant psychiatric and medical disorders. Recent studies suggest that
      RLS may be a risk factor for developing both psychiatric disorders (such as major
      depression and anxiety) and somatic diseases (such as hypertension and
      cardiovascular disease). In dialysis patients, RLS has been found to be a risk
      factor for mortality. Therefore, those with RLS who have clinically significant
      symptoms suffer increased morbidity and are at risk for impaired long-term
      medical outcomes.

PMID- 18081163
TI  - Tireless work on restless legs: guest editors' introduction.

PMID- 18081164
TI  - Update of the pathophysiology of the restless-legs-syndrome.
AB  - The Restless Legs Syndrome (RLS) is a heterogeneous disease. Symptomatic or
      secondary forms encompass iron deficiency, uremia, pregnancy, polyneuropathy, and
      other causes. The so-called idiopathic RLS syndrome preferentially affects
      patients with a younger onset before the age of 30. Here we summarize
      pathophysiological results along the anatomical route, beginning at the cortex
      and followed by the basal ganglia, thalamus, A11 neurones, substantia nigra,
      brainstem nuclei, and spinal cord. Genetic risk variants for RLS have recently
      been identified in two genes, one of them the homeobox gene MEIS1, known to be
      involved in embryonic development and variants in a second locus containing the
      genes encoding mitogen-activated protein kinase MAP2K5, and the transcription
      factor LBXCOR1. A third one, the BTBD9 gene with unknown function encodes a
      BTB(POZ) domain. Accordingly, new concepts on pathophysiology have to bridge
      conventional knowledge with possible consequences deriving from these findings.
      Furthermore, this may create a framework to help understand why dopamine, opioid,
      and some anticonvulsant therapies are effective in RLS patients.

PMID- 18081165
TI  - Genetic analyses of dopamine related genes in adult ADHD patients suggest an
      association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3
      VNTRs.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable
      psychiatric disorder in children and adults. Recent meta-analyses have indicated
      an association between genes involved in dopaminergic signaling and childhood
      ADHD, but little is known about their possible role in adult ADHD. In this study
      of adults with ADHD, we evaluated the three most commonly studied ADHD candidate
      genetic polymorphisms; the dopamine receptor D4 (DRD4) exon 3 VNTR repeat, a
      microsatellite repeat 18.5 kb upstream of the DRD5 locus and the 3'UTR dopamine
      transporter SLC6A3 (DAT 1) VNTR. We examined 358 clinically diagnosed adult
      Norwegian ADHD patients (51% males) and 340 ethnically matched controls. We found
      a nominally significant overall association with adult ADHD for the DRD5
      microsatellite marker (P = 0.04), and a trend toward increased risk associated
      with the 148-bp allele consistent with recent meta-analyses. The strongest
      overall association (P = 0.02) and increased risk for the 148-bp allele [odds
      ratio (OR) = 1.27 (95% CI: 1.00-1.61)] were seen in the inattentive and combined
      inattentive/hyperactive group as previously reported for childhood ADHD. No
      association was found for the DRD4 or SLC6A3 polymorphisms in this patient
      sample. In conclusion, our results among adults with a clinical diagnosis of ADHD
      support an association between ADHD and the DRD5 locus, but not the DRD4 or
      SLC6A3 loci. It is possible that the latter polymorphisms are associated with a
      transient form of ADHD with better long-term clinical outcome.

PMID- 18081166
TI  - Breaking bad news: a practical approach for the hospitalist.
AB  - Communicating bad news to patients and their families is a difficult but routine
      responsibility for hospitalists. Most practitioners have little or no formal
      training for this task. Preparation for, delivery of, and follow-up to these
      conversations should be deliberately planned in order to meet patients' needs. In
      this article, we review the literature that guides this process and, with a case
      example, describe steps practitioners can take to effectively deliver bad news
      and pitfalls that should be avoided. As competency in this skill set is necessary
      for effective patient care, hands-on training should be part of the core
      curriculum for all health care practitioners. Hospitalists should be proficient
      in this area and may serve as role models and instructors for colleagues and
      trainees.

PMID- 18081167
TI  - Quality of life after rectal resection and multimodality therapy.
AB  - Modern management of locally advanced rectal cancer requires a multimodality
      approach. This includes radical surgery, pelvic radiotherapy, and systemic
      chemotherapy. It can require a permanent colostomy and result in significant
      bowel, sexual, and urinary dysfunction. In order to determine the effectiveness
      of various multimodality regimens it is important to not only assess conventional
      oncologic outcomes but also the impact on patient's quality of life.

PMID- 18081168
TI  - Emerging technologies including robotics and natural orifice transluminal
      endoscopic surgery (NOTES) colorectal surgery.
AB  - Endoluminal and minimally invasive techniques have a long history and bright
      future in colorectal surgery. First, we will examine how old (colonoscopy) and
      new (laparoscopy) techniques combine in the form of laparoscopically assisted
      colonoscopic polypectomy for removal of "colonoscopically unresectable" colon
      polyps. Next, we will review the early experiences with robot-assisted minimally
      invasive colon resections. Lastly, we will introduce the next frontier in
      minimally invasive surgery, natural orifice transluminal endoscopic surgery
      (NOTES).

PMID- 18081170
TI  - Evaluation of an innovative pediatric clerkship structure using multiple outcome
      variables including career choice.
AB  - BACKGROUND: Few studies have examined alternative structures for inpatient
      clerkships. OBJECTIVE: Compare 2 inpatient clerkship structures using multiple
      outcome variables. DESIGN: Prospective, randomized controlled trial. SETTING:
      Tertiary-care, freestanding children's hospital. SUBJECTS: All medical students
      enrolled in the third-year pediatric clerkship in the 2001-2003 academic years.
      INTERVENTION: A clerkship structure consisting of an academic attending, a third
      year pediatric resident, and 4 third-year medical students, but no interns.
      MEASUREMENTS: Student end-of-rotation examinations, evaluations, a questionnaire,
      and career choices were used to evaluate the intervention. Patient logs and
      resource utilization were also assessed. Statistical analysis included evaluating
      differences between groups and measuring effect size. RESULTS: Two hundred and
      three students were randomized. Compared with those on the traditional services,
      students on the intervention service encountered more key diagnoses in the
      patients they cared for (4.4 vs. 3.6, P < .01). These students also gave higher
      ratings to their overall attitude (4.48 vs. 4.26, P = .02) and input into patient
      care decisions (4.45 vs. 3.98, P < .01). More than twice as many students on the
      intervention service matched in pediatrics (OR 2.52, 95% confidence interval 0.99
      6.38). Multivariate analysis of length of stay and total charges for selected
      patients revealed similar outcomes. CONCLUSIONS: A third-year pediatric clerkship
      that focuses on students is associated with increased satisfaction, higher
      interest in pediatrics, and consistent resource utilization. The intervention,
      therefore, merits continuation, whereas further research is required to identify
      which aspects of the intervention are responsible for its positive effects.

PMID- 18081169
TI  - The biologic significance of micrometastatic disease and sentinel lymph node
      technology on colorectal cancer.
AB  - The sentinel lymph node (SLN) technique has practical applications in multiple
      solid tumors including colorectal carcinoma. Identifying the SLN(s) provides
      better staging of the regional lymphatics beyond standard H&E analysis. This
      additional information assists in predicting biology and may be useful in guiding
      adjuvant therapy. We postulate the era of sentinel node has ushered in a new
      generation of node-negative patients; patients that have an exceptionally
      favorable outcome when compared to historic controls.

PMID- 18081171
TI  - An electronic strategy to identify hospitalized heart failure patients.
AB  - BACKGROUND: A common challenge in improving performance measures regarding heart
      failure (HF) is identifying patients early in the course of their hospitalization
      so that multidisciplinary education and clinical interventions can be
      implemented. We describe the accuracy of using an electronic pharmacy-based
      strategy to identify hospitalized patients likely to have a principal diagnosis
      of HF at discharge. METHODS: We evaluated 2 strategies. The first used the
      receipt of an intravenous loop diuretic as a single predictor; the second
      incorporated additional lab, pharmacy, and demographic information in a
      multivariable general estimating equation. RESULTS: Receipt of an intravenous
      diuretic predicted a discharge diagnosis of heart failure with a sensitivity of
      0.89 and a specificity of 0.87. Adding age, B-type natriuretic peptide level,
      previous hospitalizations, attending physician specialty, and receipt of
      spironolactone into the predictor improved the sensitivity to 0.91 and the
      specificity to 0.89. CONCLUSIONS: The receipt of intravenous loop diuretics is a
      reasonable and easily implemented screening test to identify patients likely to
      have a principal diagnosis of heart failure at discharge. The accuracy is
      improved by incorporating other electronically available variables.

PMID- 18081174
TI  - A rash decision.

PMID- 18081175
TI  - Discontinuation of antiplatelet therapy prior to low-risk noncardiac surgery in
      patients with drug-eluting stents: a retrospective cohort study.
AB  - BACKGROUND: Drug-eluting coronary stents (DESs) pose a challenge in the
      perioperative period. Sirolimus and paclitaxel may inhibit reendothelialization
      of the traumatized vessel, making it vulnerable to platelet-mediated thrombosis.
      Given the anecdotal evidence and case series suggesting that DESs may be more
      vulnerable to thrombosis on discontinuation of antiplatelet agents than are bare
      metal stents, we sought to quantify this risk. METHODS: We linked the Cleveland
      Clinic Heart Center database with the Cleveland Clinic Internal Medicine
      Preoperative Assessment Consultation and Treatment (IMPACT) Center database to
      identify all patients who had undergone DES placement at the Cleveland Clinic and
      subsequently were evaluated for noncardiac surgery between July 2003 and July
      2005. Outcome measures included 30-day rate of postoperative myocardial
      infarction (MI), DES thrombosis, major bleeding, and all-cause mortality.
      RESULTS: We identified 114 patients who underwent noncardiac surgery a median of
      236 days (IQR 125-354) after stent placement. Forty-five patients (40%) underwent
      surgery within 180 days of stenting, 15 of whom (13%) underwent surgery within 90
      days of stenting. Eighty-eight patients (77%) discontinued all antiplatelet
      agents a median of 10 days before surgery. No patients died. Two patients (1.8%,
      95% CI 0.5%-6.2%) suffered postoperative MIs, but postoperative catheterization
      showed neither had DES thrombosis (0%, 95% CI 0%-3.3%). One patient developed
      major bleeding (0.9%, CI 0.2%-4.8%). CONCLUSIONS: These data suggest that the
      overall risk of stent thrombosis is low in low-risk noncardiac surgery patients
      with DESs, particularly those who have undergone at least 180 days of
      antiplatelet therapy, even after complete discontinuation of antiplatelet agents.

PMID- 18081172
TI  - Environmental novelty is signaled by reduction of the hippocampal theta
      frequency.
AB  - The hippocampal formation (HF) plays a key role in novelty detection, but the
      mechanisms remain unknown. Novelty detection aids the encoding of new information
      into memory-a process thought to depend on the HF and to be modulated by the
      theta rhythm of EEG. We examined EEG recorded in the HF of rats foraging for food
      within a novel environment, as it became familiar over the next five days, and in
      two more novel environments unexpectedly experienced in trials interspersed with
      familiar trials over three further days. We found that environmental novelty
      produces a sharp reduction in the theta frequency of foraging rats, that this
      reduction is greater for an unexpected environment than for a completely novel
      one, and that it slowly disappears with increasing familiarity. These results do
      not reflect changes in running speed and suggest that the septo-hippocampal
      system signals unexpected environmental change via a reduction in theta
      frequency. In addition, they provide evidence in support of a cholinergically
      mediated mechanism for novelty detection, have important implications for our
      understanding of oscillatory coding within memory and for the interpretation of
      event-related potentials, and provide indirect support for the oscillatory
      interference model of grid cell firing in medial entorhinal cortex.

PMID- 18081176
TI  - Intranasal dopamine application increases dopaminergic activity in the
      neostriatum and nucleus accumbens and enhances motor activity in the open field.
AB  - Dopamine (DA) plays an important role in a number of behavioral processes and
      neurological disorders. The intranasal administration of DA provides improved
      brain penetrability in comparison to systemic administration. We investigated the
      effects of intranasal administration of DA on the activity of dopaminergic
      neurons of the mesostriatal and mesolimbic systems and on motor activity. Rats
      previously implanted with guide-cannulae in the neostriatum (NS) and nucleus
      accumbens (NAc) were submitted to microdialysis procedure under urethane
      anesthesia. Vehicle or DA (0.03, 0.3, or 3.0 mg/kg) was administered bilaterally
      into the nostrils. In a separate study, animals received an intraperitoneal
      (i.p.) injection of vehicle or DA (0.03, 0.3, 3.0, or 30.0 mg/kg). Samples were
      collected every 10 min and analyzed for the content of DA and metabolites using
      high-performance liquid chromatography. For the open field study, rats were given
      intranasal vehicle or DA (0.03, 0.3, or 3.0 mg/kg) and placed into the field for
      30 min. Motor activity (locomotion and rearing) and grooming were analyzed in
      blocks of 10 min using Ethovision. Intranasal DA (3.0 mg/kg) significantly
      increased DA levels in the NS and NAc immediately after administration. A
      comparable effect was obtained only after i.p. administration of 30 mg/kg DA. In
      the open field, the 3.0 mg/kg dose significantly decreased grooming behavior in
      the second 10 min interval and significantly increased locomotor activity in the
      third 10 min interval. The data indicate that intranasal administration of DA can
      influence dopaminergic functions and motor activity, and has a potential
      application in the therapy of diseases affecting the dopaminergic system.

PMID- 18081177
TI  - In the eye of the storm.

PMID- 18081178
TI  - Klebsiella pneumoniae endophthalmitis with associated hepatic abscess.
AB  - Klebsiella pneumoniae liver abscess is known to be associated with metastatic
      endophthalmitis, with most cases clustered in Taiwan. We report a case of
      Klebsiella liver abscess with metastatic endophthalmitis in a nondiabetic Haitian
      man without underlying medical problems.

PMID- 18081179
TI  - Color-coded wristbands: promoting safety or confusion?

PMID- 18081180
TI  - Asymmetric muscle atrophy from childhood polio.

PMID- 18081181
TI  - The enduring effects of an adolescent social stressor on synaptic density, part
      II: Poststress reversal of synaptic loss in the cortex by adinazolam and MK-801.
AB  - Experience programs synaptic development to match the needs of the environment.
      This process depends on the nature and timing of the experience. Exposure to
      stress during adolescence selectively reduces synaptic density in the prefrontal
      cortex (a later maturing region), while sparing hippocampal synapses (an earlier
      maturing region). To determine whether the anatomical effects of an adolescent
      social stressor in rats endures into adulthood and are reversible, male subjects
      were isolation or group housed between days 30 and 35 and then treated with
      vehicle, adinazolam, MK-801, or tianeptine between days 40 and 55. At day 60,
      immunohistochemistry revealed a 13.5% +/- 5.3% reduction in synaptophysin in the
      infralimbic cortex and cingulate gyrus in isolation-housed subjects. MK-801 and
      adinazolam restored cortical synaptic density to within 2% of group-housed
      values, suggesting that the synaptic loss induced by stress during adolescence is
      modulated through reduced glutamatergic activity directly by NMDA antagonism or
      indirectly by enhancing GABAergic activity. Tianeptine did not modulate
      adolescent stress effects in the prefrontal cortex. None of these drugs increased
      cortical synaptophysin in group-housed controls. Increased synaptophysin was
      observed in the group-housed condition in the hippocampus, striatum, and nucleus
      accumbens following drug exposure. Although stress did not decrease synaptic
      density in these regions, drug exposure failed to increase synaptic density when
      compared with the controls. Taken together, stress-induced changes in cortical,
      but not hippocampal, synaptic density initiated during adolescence endure into
      adulthood. These cortical changes can be reversed through a reduction of
      glutamatergic activity, but not serotonin augmentation.

PMID- 18081182
TI  - Oscillatory firing of dopamine neurons: differences between cells in the
      substantia nigra and ventral tegmental area.
AB  - Neuronal oscillations have been suggested to play an important role in
      information processing in the brain. Using spectral analysis, we have recently
      shown that the repetitive burst-like firing in many dopamine (DA) neurons in the
      ventral tegmental area (VTA) can be described as a slow oscillation (SO) in
      firing rate. In this study, we examined whether DA neurons in the adjacent
      substantia nigra (SN) also display a SO. DA neurons were recorded extracellularly
      using the cells/track technique in chloral hydrate-anesthetized rats. Spectral
      analysis showed that firing patterns of SN DA neurons exhibited a SO similar to
      that observed in VTA DA neurons. The amplitude of the SO, however, was much
      reduced in the SN compared with that in the VTA and so was the number of DA
      neurons qualified as high-SO cells. In high-SO DA neurons, the amplitude of the
      SO was strongly correlated with the degree of bursting, and this correlation was
      observed in both the VTA and SN. In low-SO cells, however, the SO was more
      significantly correlated with the variability of firing than with firing rate and
      bursting. Since the generation of the SO depends on afferent inputs to DA
      neurons, a better understanding of its difference between the SN and VTA may
      provide important insights into the neural networks that control DA neurons in
      the two areas.

PMID- 18081183
TI  - Pharmacological MRI in awake rats predicts selective binding of alpha4beta2
      nicotinic receptors.
AB  - Neuronal nicotinic receptors are the subject of intensive research focused on
      developing novel therapies for drug abuse, neurocognitive disorders,
      neurodegenerative diseases, and pain. In this study, we have applied
      pharmacological magnetic resonance imaging (phMRI) in awake rats to map
      functional brain responses to the selective alpha(4)beta(2) nicotinic receptor
      agonists, A-85380, and ABT-594. Moreover, we have validated our methods by
      comparison with autoradiography using [(3)H]-A-85380 and [(3)H]-ABT-594. Under
      awake conditions (no anesthesia during scanning) where rats were habituated to
      the imaging environment, both compounds increased regional cerebral blood volume
      (rCBV) across multiple brain regions that closely matched regional brain receptor
      distribution with the same tritiated compounds. In addition, regional ABT-594
      induced rCBV changes under awake conditions were also derived and characterized
      using a pharmacological model. Area-under-curve and maximum rCBV changes in brain
      were found to be dose-related and region-specific, and corresponded well with the
      known preclinical behavioral profile of this drug. In contrast, under conditions
      of alpha-chloralose anesthesia where physiological variables were maintained
      within normal ranges, increases in rCBV induced by ABT-594 were primarily
      restricted to some cortical areas and did not agree well with autoradiography
      data. Our data demonstrate the utility of using phMRI in awake animals to
      characterize selective pharmacological action but also highlight an important
      confound (anesthesia) that is rarely considered in preclinical phMRI studies.

PMID- 18081184
TI  - Neurotoxic-related changes in tyrosine hydroxylase, microglia, myelin, and the
      blood-brain barrier in the caudate-putamen from acute methamphetamine exposure.
AB  - Changes in the histological morphology of the caudate-putamen (CPu) were
      determined after a high-dose methamphetamine (METH) exposure in an effort to
      elucidate whether BBB disruption plays a role in CPu neurotoxicity. This was
      accomplished by evaluating the tyrosine hydroxylase immunoreactivity (TH-IR),
      isolectin B4 reactivity, Black Gold II (BG-II) and Fluoro-Jade C (FJ-C) staining,
      and immunoreactivity to mouse immunoglobulin G (IgG-IR) in adult male mice at 90
      min, 4-h, 12-h, 1-day, and 3-day post-METH exposure. The IgG-IR indicated that
      the BBB was only modestly altered in the CPu at time points after
      neurodegeneration occurred and dependent on hyperthermia and status epilepticus.
      The modest CPu IgG-IR changes observed in the perivascular areas indicated that
      immunoglobulins were present on some CPu microglia 1 day or more after METH. The
      first signs of CPu damage were swellings in the TH-IR axons, myelin damage, and a
      few degenerating neurons at 4-h post-METH. The loss of TH-IR was dependent on
      hyperthermia but not seizures or CPu neurodegeneration, and the TH-IR was
      virtually absent throughout the CPu within 12 h. Surprisingly, signs of FJ-C
      labeling (degenerating) axons in the CPu were seen only in the regions of
      pronounced somatic neurodegeneration and independent of TH-IR loss. Microglial
      activation did not occur until 1 day or more post-METH. In summary, a major BBB
      disruption within the CPu does not directly contribute to neurotoxicity in this
      single high-dose METH exposure. However, seizure activity produced or exacerbated
      by amygdalar BBB disruption can significantly increase CPu somatic
      neurodegeneration (but not affect dopamine (DA) terminal damage). The time course
      of microglial activation indicates a response to the neurodegeneration, myelin
      damage, and/or damaged DA terminals after loss of TH-IR.

PMID- 18081186
TI  - Masa--hospitalist.

PMID- 18081185
TI  - A randomized clinical trial to compare the use of safety net enclosures with
      standard restraints in agitated hospitalized patients.
AB  - BACKGROUND: Although hospitals attempt to minimize the use of restraints, certain
      cases require their application. For such patients, there is a need for novel,
      safe and more humane restraint systems. OBJECTIVE: To assess the acceptability
      and efficacy of safe enclosures in agitated hospitalized patients. DESIGN: Single
      centered randomized controlled trial. SETTING: Community hospital. PATIENTS:
      Agitated hospitalized patients requiring restraint. INTERVENTION: Patients were
      randomized to either standard restraints or the safe enclosure. We used the SOMA
      Safe Enclosure. MEASUREMENTS: Perception scores of relatives, physicians, and
      nurses; agitation scores of patients (assessed using the Agitated Behavior Scale
      (ABS) and the Alcohol Withdrawal Assessment Form (AWAF)); length of stay; time in
      restraints; total dose of medication used to treat agitation; and injuries.
      RESULTS: Of the 49 patients randomized, 20 were assigned to the safe enclosure
      group and 29 were assigned to the standard restraint group. Relatives, physicians
      and secondary nurses rated the safe enclosure more positively than standard
      restraints (P < .001, P < .001, P = .023, respectively). There was no difference
      between groups in level of agitation (AWA at 48 hours, P = .8516; ABS at 48
      hours, P = .3743); length of stay (P = .3077); time in restraints (P = .5745);or
      total dose of medication (anti-anxiety medications, P = .5607; anti-psychotic
      medications, P = .7858). There was one injury to a patient in the standard
      restraint group and none in the safe enclosure group. CONCLUSIONS: For
      hospitalized patients requiring restraint, the SOMA Safe Enclosure is effective
      and more acceptable to relatives, physicians, and secondary nurses than currently
      used restraints.

PMID- 18081187
TI  - Effects of rapid response systems on clinical outcomes: systematic review and
      meta-analysis.
AB  - BACKGROUND: A rapid response system (RRS) consists of providers who immediately
      assess and treat unstable hospitalized patients. Examples include medical
      emergency teams and rapid response teams. Early reports of major improvements in
      patient outcomes led to widespread utilization of RRSs, despite the negative
      results of a subsequent cluster-randomized trial. PURPOSE: To evaluate the
      effects of RRSs on clinical outcomes through a systematic literature review. DATA
      SOURCES: MEDLINE, BIOSIS, and CINAHL searches through August 2006, review of
      conference proceedings and article bibliographies. STUDY SELECTION: Randomized
      and nonrandomized controlled trials, interrupted time series, and before-after
      studies reporting effects of an RRS on inpatient mortality, cardiopulmonary
      arrests, or unscheduled ICU admissions. DATA EXTRACTION: Two authors
      independently determined study eligibility, abstracted data, and classified study
      quality. DATA SYNTHESIS: Thirteen studies met inclusion criteria: 1 cluster
      randomized controlled trial (RCT), 1 interrupted time series, and 11 before-after
      studies. The RCT showed no effects on any clinical outcome. Before-after studies
      showed reductions in inpatient mortality (RR = 0.82, 95% CI: 0.74-0.91) and
      cardiac arrest (RR = 0.73, 95% CI: 0.65-0.83). However, these studies were of
      poor methodological quality, and control hospitals in the RCT reported reductions
      in mortality and cardiac arrest rates comparable to those in the before-after
      studies. CONCLUSIONS: Published studies of RRSs have not found consistent
      improvement in clinical outcomes and have been of poor methodological quality.
      The positive results of before-after trials likely reflects secular trends and
      biased outcome ascertainment, as the improved outcomes they reported were of
      similar magnitude to those of the control group in the RCT. The effectiveness of
      the RRS concept remains unproven.

PMID- 18081188
TI  - Functional reconstruction of traumatic loss of flexors in forearm with
      gastrocnemius myocutaneous flap transfer.
AB  - Reconstruction of flexor function of forearm remains a challenge in the
      reconstructive surgery. With development of microsurgical techniques,
      reconstructive surgeons have been able to envision muscle transplantation for
      restoration of function and not simply for provision of soft tissue coverage. In
      this report, we present our experience in three patients of successful treatment
      of traumatic flexor loss in the forearm with the microsurgical medial
      gastrocnemius myocutaneous flap. At 18- to 24-months follow-up, the detected
      action potential (Latency and Amplity) in the transferred muscle was
      significantly improved in the EMG examination. The strength of the digital
      flexion reached to III degree in one case, IV degree in two cases. No
      complications were noted in the donor legs. We conclude that the microsurgical
      medial gastrocnemius myocutaneous flap transfer can be an ideal alternative for
      functional reconstruction of the forearm flexor muscle in three posttrauma
      patients.

PMID- 18081189
TI  - Deformity of lumbar spine after selective dorsal rhizotomy for spastic cerebral
      palsy.
AB  - To observe the effect of selective dorsal rhizotomy (SDR) on the deformity of the
      lumbar spine, a retrospective review was conducted from October 1992 to December
      2002 on children who had undergone SDR in our department, and in whom
      preoperative and postoperative spine radiographs had been obtained. The angles of
      hyperlordolysis were measured. The study group comprised 219 patients, in which
      61 cases were followed up and examined between May 2004 and February 2005. The
      mean age at surgery was 6.9 years (range 3-20 years), with a mean time to recent
      follow-up radiographs of 6.3 years (5-9 years). A total 219 children underwent
      laminectomy from L(2)-S(1). Scoliosis existed in one case, and two cases of L(5)
      spondylolysis were detected before surgery. One case presented lumbar
      hyperlordosis. After SDR, 10 cases showed distinctively abnormal walking posture
      of hyperlordolysis. Compared with the preoperative angle of hyperlordolysis, the
      angle was improved after the operation. Among them, four patients developed
      spondylolysis and spondylolisthesis (grade I). We also observed that one case
      developed lumbar kyphosis deformity. In conclusion, cerebral palsy patients may
      develop spinal deformity. Some cases showed distinctively abnormal walking
      posture of hyperlordolysis, and they developed spondylolysis and
      spondylolisthesis after surgery.

PMID- 18081190
TI  - Growth in the larval zebrafish pectoral fin and trunk musculature.
AB  - After initial patterning, muscle in the trunk and fins of teleosts grows
      extensively. Here, we describe muscle growth in zebrafish, with emphasis on the
      pectoral fin musculature. In the trunk, slow muscle fibers differentiate first.
      In contrast, slow muscle does not appear in the pectoral fin until the beginning
      of the juvenile period. Mosaic hyperplasia contributes to trunk muscle growth,
      and new fibers are apparent within the muscle as early as 6 mm standard length.
      In the pectoral fin muscle, mosaic hyperplasia is not evident at any examined
      stage. Instead, the predominant mode of hyperplasia is stratified. In larval
      pectoral fin muscle new fibers appear subjacent to the skin, and this correlates
      with the expression of myogenic genes such as muscle regulatory factors and Pax7.
      Our results suggest that regulation of fiber type development and muscle growth
      may differ in the pectoral fin and trunk.

PMID- 18081191
TI  - Proteome analysis of Streptococcus suis serotype 2.
AB  - Outbreaks in humans, caused by Streptococcus suis serotype 2 (SS2), were reported
      in 1998 and 2005 in China. However, the mechanism of SS2-associated infection
      remains unclear. For the first time, a 2-D gel approach combined with MS was used
      to establish a comprehensive 2-D reference map for aiding our understanding of
      the pathogenicity of SS2. The identification of 694 out of 834 processed spots
      revealed 373 proteins. Most of the identified proteins were located in the
      cytoplasm and were involved in energy metabolism, protein synthesis, and cellular
      processes. Proteins that were abundant in the 2-DE gels could be linked mainly to
      housekeeping functions in carbohydrate metabolism, protein quality control and
      translation. 2-DE of secretory proteins was performed using IPG strips of pH 4-7.
      Among the 102 protein spots processed, 87 spots representing 77 proteins were
      successfully identified. Some virulence-associated proteins of SS2 were found,
      including arginine deiminase, ornithine carbamoyl-transferase, carbamate kinase,
      muramidase-released protein precursor, extracellular factor, and suilysin.
      Enolase and endopeptidase have been proposed as putative virulence-associated
      factors in this study. The 2-D reference map might provide a powerful tool for
      analyzing the virulence factor and the regulatory network involved in the
      pathogenicity of this microorganism.

PMID- 18081192
TI  - Highly selective and rapid enrichment of phosphorylated peptides using gallium
      oxide-coated magnetic microspheres for MALDI-TOF-MS and nano-LC-ESI-MS/MS/MS
      analysis.
AB  - In this work, we present, to our knowledge, the first demonstration of the
      utility of iron oxide magnetic microspheres coated with gallium oxide for the
      highly selective enrichment of phosphopeptide prior to mass spectrometric
      analysis. These microspheres that we prepared not only have a shell of gallium
      oxide, giving them a high-trapping capacity for the phosphopeptides, but also
      their magnetic property enables easy isolation by positioning an external
      magnetic field. Tryptic digest products of phosphoproteins including beta-casein,
      ovalbumin, casein, as well as five protein mixtures were used as the samples to
      exemplify the feasibility of this approach. In very short time (only 0.5 min),
      phosphopeptides sufficient for characterization by MALDI-TOF-MS were selectively
      enriched by the Ga(2)O(3)-coated Fe(3)O(4) microspheres. The performance of the
      Ga(2)O(3)-coated Fe(3)O(4) microspheres were further compared with Fe(3+)
      immobilized magnetic silica microspheres, commercial Fe(3+)-IMAC resin, and TiO2
      beads for enrichment of peptides originating from tryptic digestion of beta
      casein and BSA with a molar ratio of 1:50, and the results proved a stronger
      selective ability of Ga(2)O(3)-coated Fe(3)O(4) microspheres over the other
      materials. Finally, the Ga(2)O(3)-coated Fe(3)O(4) microspheres were successfully
      utilized for enrichment of phosphopeptides from digestion products of rat liver
      extract. All results show that Ga(2)O(3)-coated Fe(3)O(4) microsphere is an
      effective material for selective isolation and concentration of phosphopeptides.

PMID- 18081195
TI  - Measurement error in the explanatory variable of a binary regression: regression
      calibration and integrated conditional likelihood in studies of residential radon
      and lung cancer.
AB  - In epidemiology, one approach to investigating the dependence of disease risk on
      an explanatory variable in the presence of several confounding variables is by
      fitting a binary regression using a conditional likelihood, thus eliminating the
      nuisance parameters. When the explanatory variable is measured with error, the
      estimated regression coefficient is biased usually towards zero. Motivated by the
      need to correct for this bias in analyses that combine data from a number of case
      control studies of lung cancer risk associated with exposure to residential
      radon, two approaches are investigated. Both employ the conditional distribution
      of the true explanatory variable given the measured one. The method of regression
      calibration uses the expected value of the true given measured variable as the
      covariate. The second approach integrates the conditional likelihood numerically
      by sampling from the distribution of the true given measured explanatory
      variable. The two approaches give very similar point estimates and confidence
      intervals not only for the motivating example but also for an artificial data set
      with known properties. These results and some further simulations that
      demonstrate correct coverage for the confidence intervals suggest that for
      studies of residential radon and lung cancer the regression calibration approach
      will perform very well, so that nothing more sophisticated is needed to correct
      for measurement error.

PMID- 18081197
TI  - Substituent effects on 13C chemical shifts of alkyl-substituted 4-oxo-1,3
      dioxolanes and 5-oxo-1,3-oxathiolanes.
AB  - The 13C NMR chemical shifts for 4-oxo-1,3-dioxolane (1) and its all methyl
      substituted derivatives (2-10) as well as for 5-oxo-1,3-oxathiolane (11) and its
      nine alkyl-substituted derivatives (12-20) are reported. The magnitude and
      variety of the substituent effects are in accordance with the envelope
      conformations in which the oxygen or sulfur atom locates at the tip of the
      envelope as postulated on the basis of earlier data.

PMID- 18081196
TI  - A novel stepwise analysis procedure of genome-wide expression profiles identifies
      transcript signatures of thiamine genes as classifiers of mitochondrial mutants.
AB  - To extract functional information on genes and processes from large expression
      datasets, analysis methods are required that can computationally deal with these
      amounts of data, are tunable to specific research questions, and construct
      classifiers that are not overspecific to the dataset at hand. To satisfy these
      requirements, a stepwise procedure that combines elements from principal
      component analysis and discriminant analysis, was developed to specifically
      retrieve genes involved in processes of interest and classify samples based upon
      those genes. In a global expression dataset of 300 gene knock-outs in
      Saccharomyces cerevisiae, the procedure successfully classified samples with
      similar 'cellular component' Gene Ontology annotations of the knock-out gene by
      expression signatures of limited numbers of genes. The genes discriminating
      'mitochondrion' from the other subgroups were evaluated in more detail. The
      thiamine pathway turned out to be one of the processes involved and was
      successfully evaluated in a logistic model to predict whether yeast knock-outs
      were mitochondrial or not. Further, this pathway is biologically related to the
      mitochondrial system. Hence, this strongly indicates that our approach is
      effective and efficient in extracting meaningful information from large
      microarray experiments and assigning functions to yet uncharacterized genes.

PMID- 18081198
TI  - Electrophoresis of a charge-regulated toroid normal to a large disk.
AB  - The electrophoresis of a charge-regulated toroid (doughnut-shaped entity) normal
      to a large disk is investigated under the conditions of low surface potential and
      weak applied electric field. The system considered is capable of modeling the
      electrophoretic behavior of various types of biocolloids such as bacterial DNA,
      plasmid DNA, and anabaenopsis near a perfectly conducting planar wall. The
      influences of the size of the toroid, the separation distance between the toroid
      and the disk, the charged conditions on the surfaces of the toroid and the disk,
      and the thickness of electric double layer on the electrophoretic mobility of the
      toroid are discussed. The results of numerical simulation reveal that under
      typical conditions the electrophoretic behavior of the toroid can be different
      from that of an integrated entity. For instance, if the surface of the toroid
      carries both acidic and basic functional groups, its mobility may have a local
      maximum as the thickness of double layer varies. We show that the electrophoretic
      behavior of the toroid is different, both qualitatively and quantitatively, from
      that of the corresponding integrated particle (particle without hole).

PMID- 18081199
TI  - Response surface examination of the relationship between experimental conditions
      and product distribution in electrophoretically mediated microanalysis.
AB  - This work presents the first known use of response surface methodology (RSM) in
      electrophoretically mediated microanalysis. This concept is demonstrated by
      examining the optimization of reaction conditions for the conversion of
      nicotinamide adenine dinucleotide to nicotinamide adenine dinucleotide, reduced
      form by glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) in the conversion
      of glucose-6-phosphate to 6-phosphogluconate. Experimental factors including
      voltage, enzyme concentration, and mixing time of reaction at the applied voltage
      were selected at three levels and tested in a Box-Behnken response surface
      design. Upon migration in a capillary under CE conditions, plugs of substrate and
      enzyme are injected separately in buffer and allowed to react at variable
      conditions. Extent of reaction and product ratios were subsequently determined by
      CE. The model predicted results are shown to be in good agreement (7.1%
      discrepancy difference) with experimental data. The use of chemometric RSM
      provides a direct relationship between electrophoretic conditions and product
      distribution of microscale reactions using CE, thereby offering a new and
      versatile approach to optimizing enzymatic experimental conditions.

PMID- 18081200
TI  - Signal modelization for improved precision of assessment of minimum and mean
      telomere lengths.
AB  - Telomere length is an important measure of cell and tissue regenerative
      capacities. The mean telomere length is classically used as global indicator of a
      tissue telomere length. In skeletal muscle, which is made of postmitotic
      myonuclei and satellite cells (muscle stem cells), minimum telomere length is
      also used to assess the telomere length of satellite cells and newly incorporated
      myonuclei. At present, the estimation of the method reproducibility during the
      assessment of mean and minimum telomere length using Southern blot analysis has
      never been documented. The aim of this report is to describe a signal
      modelization for improved precision of assessment of minimum and mean telomere
      lengths and to document the method reproducibility. Telomeres are assessed using
      a Southern technique where the gel is directly hybridized with the specific probe
      without the membrane-transferring step in order to prevent telomeric low signal
      loss. We found that the improved signal analysis for determination of telomere
      length is associated with coefficients of variation ranging from 1.37 to 4.29%
      for the mean telomeric restriction fragment (TRF) length and from 2.04 to 4.95%
      for the minimum TRF length. Improved method reproducibility would allow saving
      time and biological material as duplicate and triplicate measurement of the same
      sample is no longer required.

PMID- 18081201
TI  - Nanoliter-volume protein enrichment, tryptic digestion, and partial separation
      based on isoelectric points by CE for MALDI mass spectral analysis.
AB  - Sequence-specific proteolysis is an important part of protein identification by
      MS. Digestion of protein is commonly performed in-solution, in sample vials with
      volumes ranging from milli- to microliters. When digestion is performed with a
      sample volume below 1 microL, handling of solution and potential sample loss via
      adsorption become significant issues. In this report, a proof of concept for the
      digestion of a small volume protein solution inside a capillary was demonstrated
      using a discontinuous buffer system previously studied (Nesbitt, C. A., et al. J.
      Chromatogr. A 2005, 1073, 175-180). Upon voltage application, a pH junction was
      created by the discontinuous buffer. Using myoglobin as an example, the protein
      molecules were enriched at the junction with an estimated volume of a few
      nanoliters. A protease, trypsin, was then introduced to myoglobin at the junction
      by coenrichment to induce in-capillary digestion. The voltage application was
      then suspended to provide the necessary time (2 h) for the proteolysis to
      proceed. When completed, voltage application was resumed, and the discontinuous
      buffer reconcentrated the peptides formed from digestion. Importantly, the
      refocused peptides appeared to roughly elute according to their pIs, resulting in
      a partial separation. Direct sample deposition from capillary was performed to
      facilitate mass spectral analysis by MALDI. The partial separation, according to
      pI, offered the potential benefits of MALDI MS signal enhancement and provided
      supplementary pI information for peptide identity assignment.

PMID- 18081202
TI  - CE coupled with amperometric detection using a boron-doped diamond
      microelectrode: validation of a method for endogenous norepinephrine analysis in
      tissue.
AB  - The level of endogenous norepinephrine (NE) in several tissue types was
      determined by CE with amperometric detection. We report herein on the method
      validation by HPLC using both amperometric and coulometric detection (CD). Keys
      to the method were the use of a diamond microelectrode for detection and off-line
      SPE for sample preparation. The run buffer was a 250 mM borate solution adjusted
      to pH 8.8 with potassium hydroxide. The diamond microelectrode exhibited a low
      and stable background current, and a low peak-to-peak noise < or =0.65 pA at the
      detection potential of +0.86 V versus Ag/AgCl. For standard solutions, the
      detector signal (i.e., oxidation current) changed linearly with the NE
      concentration (r(2) = 0.999) between 60 and 1000 nmol/L with an estimated LOD of
      51 nmol/L (S/N = 3) and a response variability of 4.5% (RSD, n = 5). An Oasis MCX
      sorbent was used for SPE and the procedure produced an NE recovery of 95.1 +/-
      5.6% (n = 6) from tissue homogenates. NE levels in the spleen, small intestine,
      and heart of a normotensive rat were found to be in the range of 0.77-0.97, 0.22
      0.32, and 0.29-0.45 microg/g tissue (n = 3), respectively.

PMID- 18081203
TI  - Statistical data processing of mobility curves of univalent weak bases.
AB  - This paper brings a new rigorous and complete statistical approach to the data
      processing of the mobility curves of univalent weak bases. This approach is based
      on application of the least square method to the equation of the related mobility
      curve. Thus, an equation for the best fit is derived and its mathematical
      solution is found. The solution brings best estimates of the mobility curve
      parameters, i.e., dissociation constant K and ionic mobility of the protonated
      base U. Further, explicit formulas have been derived for the calculation of
      related statistical parameters, i.e., SDs of effective mobility s(u), of the
      dissociation constant s(K), and of ionic mobility of protonated base s(U). The
      mathematical functions used in the above approach do not impose any limitations
      on the data used, i.e., the mobility and pH values used may be real numbers
      (positive, negative, zero).

PMID- 18081204
TI  - Thermodynamical studies of designed ligands binding to Cel7A using partial
      filling capillary electrophoresis.
AB  - A convenient experimental method for thermodynamical studies based on partial
      filling affinity CE is presented. The advantages of this approach are the
      possibility to determine binding energies from relatively weak interactions as
      well as the small amounts of samples consumed. In order to explore the affinity
      and selectivity of the cellobiohydrolase Cel7A, a number of propranolol analogues
      were recently designed. The affinities of a selection of these ligands were
      determined in the temperature interval 15-40 degrees C, and DeltaG degrees ,
      DeltaH degrees and DeltaS degrees were obtained by means of Van't Hoff plots.
      Through these experiments, the importance of the entropy contribution in the
      complexation between the ligands and Cel7A has been demonstrated.

PMID- 18081205
TI  - Fast fluorescent staining of protein in sodium dodecyl sulfate polyacrylamide
      gels by palmatine.
AB  - A fast and sensitive protein fluorescent detection method in SDS-PAGE using the
      natural product palmatine is described. Palmatine is an alkaloid found in various
      plants exhibiting a broad spectrum of antibiotic activity in humans. The
      sensitivity of palmatine staining is similar to those of the SYPRO Red, SYPRO
      Tangerine, and SYPRO Orange protein gel stains - about 4 ng per protein band.
      This detection sensitivity is comparable to colloidal CBB staining. Since
      proteins stained with palmatine do not need destaining, the staining procedure
      can be easily shortened and completed in about 30 min. Stained proteins can be
      photographed using a UV transilluminator. The results of the present study
      suggest that the palmatine staining is sensitive, rapid, low cost, and safe for a
      broad application to the research of protein.

PMID- 18081206
TI  - Flavan-3-ols: nature, occurrence and biological activity.
AB  - Representing the most common flavonoid consumed in the American diet, the flavan
      3-ols and their polymeric condensation products, the proanthocyanidins, are
      regarded as functional ingredients in various beverages, whole and processed
      foods, herbal remedies and supplements. Their presence in food affects food
      quality parameters such as astringency, bitterness, sourness, sweetness, salivary
      viscosity, aroma, and color formation. The ability of flavan-3-ols to aid food
      functionality has also been established in terms of microbial stability,
      foamability, oxidative stability, and heat stability. While some foods only
      contain monomeric flavan-3-ols [(-)-epicatechin predominates] and dimeric
      proanthocyanidins, most foods contain oligomers of degree of polymerization
      values ranging from 1-10 or greater than 10. Flavan-3-ols have been reported to
      exhibit several health beneficial effects by acting as antioxidant,
      anticarcinogen, cardiopreventive, antimicrobial, anti-viral, and neuro-protective
      agents. This review summarizes the distribution and health effects of these
      compounds.

PMID- 18081208
TI  - Estimation of chromatographic parameters on two silica-based columns connected in
      series under nonaqueous reversed phase liquid chromatographic conditions.
AB  - Empirical equations were produced to relate important chromatographic parameters
      on two silica-based columns serially linked, in isocratic nonaqueous RP HPLC, to
      retention times and peak widths of the separated compounds on the individual
      columns. These equations were derived because the experimental data seemed to
      deviate from the values expected, applying basic chromatographic theoretical
      equations. The chromatographic parameters studied were retention time, peak
      width, resolution, number of theoretical plates, capacity factor, and separation
      factor. In addition, empirical linear relationships were produced for the
      estimation of the above mentioned parameters of the serial systems, in direct and
      reverse order, relating them to those obtained on each column, separately. The
      experimentally obtained values were in good agreement with those estimated by the
      derived equations.

PMID- 18081207
TI  - Phenolic compounds: evidence for inhibitory effects against obesity and their
      underlying molecular signaling mechanisms.
AB  - Phenolic compounds are widely present in the plant kingdom. Many epidemiological
      studies have indicated that consumption of some plant-derived foodstuffs with
      high phenolic content is associated with the prevention of some diseases and that
      these compounds may have similar properties to antioxidants, antimutagenic
      agents, antithrombotic agents, anti-inflammatory agents, anti-HIV-1, and
      anticancer agents. However, obesity is an important topic in the world of public
      health and preventive medicine. Relationships between body mass index, waist
      circumference, or waist-to-hip ratio and the risk of development of some diseases
      (such as heart disease, dyslipidemia, hypertension, non-alcoholic fatty liver
      disease, diabetes, kidney failure, cancer, stroke, osteoarthritis, and sleep
      apnea) have been observed. Evidence that phenolic compounds have beneficial
      effects in fighting obesity is increasingly being reported in the scientific
      literature. These in vitro and in vivo effects of phenolic compounds on the
      induction of pre-adipocytic and adipocytic apoptosis and inhibition of adipocytic
      lipid accumulation are considered in detail here. This review presents evidence
      of their inhibitory effects on obesity and their underlying molecular signaling
      mechanisms.

PMID- 18081209
TI  - Development of an HPLC multi-residue method for the determination of ten
      quinolones in bovine liver and porcine kidney according to the European Union
      Decision 2002/657/EC.
AB  - A sensitive multi-residue analytical method was developed for the determination
      of ten quinolones: enoxacin, ofloxacin, norfloxacin, ciprofloxacin, danofloxacin,
      enrofloxacin, sarafloxacin, oxolinic acid, nalidixic acid, and flumequine in
      bovine liver and porcine kidney. A simple liquid extraction step followed by a
      solid phase extraction clean up procedure was applied for the extraction of
      quinolones from liver and kidney tissues. Recoveries of the extraction varied
      between 82 and 88% for bovine liver and 92 and 95% for porcine kidney. Separation
      was performed on an ODS-3 PerfectSil Target (250 x 4 mm) 5 microm analytical
      column at 25 degrees C. The mobile phase consisted of a mixture of TFA 0.1%
      CH(3)CN-CH(3)OH, delivered at a flow rate of 1.2 mL/min according to a gradient
      program. Elution of quinolones and the internal standard (caffeine, 7.5
      ng/microL) was complete within 27 min. Photodiode array detection was used for
      monitoring the eluants at 275 and 255 nm. The method was fully validated
      according to the European Union Decision 2002/657/EC, determining linearity,
      selectivity, decision limit, detection capability, accuracy, and precision. The
      LODs of the specific method of quinolone determination in bovine liver varied
      between 3 and 7 microg/kg and in porcine kidney between 3 and 4 microg/kg.

PMID- 18081210
TI  - GC-MS analysis of organic compounds in wastewater and sewage sludge.
AB  - A multimethod based on liquid-liquid extraction and solid-liquid extraction for
      the analysis of persistent organic pollutants in water and sludge from sewage
      treatment plants has been established. Traces of 22 organic compounds used in
      industry and personal care products (PCPs) were analyzed by GC/MS. The LODs for
      the analytes were less than 2.3 ng/L for wastewater and 31 microg/kg (dry weight
      matter) for sewage sludge. Satisfactory recoveries (70-130%) were achieved. The
      validated method permits the analysis of water and sludge samples at various
      stages of the treatment from different sewage treatment plants. Thus, the
      distribution between water and sludge as well as the dissipation of the compounds
      analyzed were balanced. By this means, the efficiency of different wastewater
      treatment plants (WWTPs) can be evaluated and measures can be taken to optimize
      the treatment process at different stages.

PMID- 18081212
TI  - High-resolution solid-state MAS NMR of proteins-Crh as an example.
AB  - Solid-state NMR spectroscopy provides unique possibilities for the structural
      investigation of insoluble molecules at the atomic level. Recent efforts aim at
      solving the complete structures of biological macromolecules using high
      resolution magic angle spinning NMR. Structurally homogenous samples of
      [(13)C,(15)N]-labeled proteins have to be used in this type of studies.
      Microcrystalline model proteins present valuable tools for the developments of
      methods towards this goal. This review discusses recent progress in the field,
      using the Crh protein as an illustrative example. We discuss strategies for
      resonance assignments and for the determination of structure and dynamics, as
      well as techniques for the detection of protein interaction partners and folding
      mechanisms by solid-state NMR methods.

PMID- 18081213
TI  - Chromatographic NMR: a tool for the analysis of mixtures of small molecules.
AB  - The addition of a solid to a mixture of small molecules introduces variations on
      the average translational mobility of these latter, proportional to the affinity
      of a given moiety for the less-mobile phase. This effect is at the basis of
      chromatographic separation, but can be used to simplify the NMR analysis of
      mixtures as well. In fact, as the induced differences in molecular mobility can
      span orders of magnitude, it becomes a much easier task to split the overall NMR
      spectrum of the mixture into one of the pure components using pulsed field
      gradient (PFG) methods. We have demonstrated recently this approach, in the
      context of HRMAS (high-resolution magic angle spinning) NMR, as required to
      recover high-resolution spectra in solid/liquid mixtures. In this review, we
      shall cover some of the principles and the practicality of this HRMAS-PFG
      approach for the study of mixtures. A comparison of the actual (in LC) and
      virtual (in NMR) separation capabilities of a few combinations of solid phase
      material/solvent composition shows similarities but also some striking
      differences: bare (not functionalized) silica expresses a superior potential for
      resolving spectral components than expected on the basis of the LC outcome.

PMID- 18081214
TI  - Developing strategies for detection of gene doping.
AB  - It is feared that the use of gene transfer technology to enhance athletic
      performance, the practice that has received the term 'gene doping', may soon
      become a real threat to the world of sport. As recognised by the anti-doping
      community, gene doping, like doping in any form, undermines principles of fair
      play in sport and most importantly, involves major health risks to athletes who
      partake in gene doping. One attraction of gene doping for such athletes and their
      entourage lies in the apparent difficulty of detecting its use. Since the
      realisation of the threat of gene doping to sport in 2001, the anti-doping
      community and scientists from different disciplines concerned with potential
      misuse of gene therapy technologies for performance enhancement have focused
      extensive efforts on developing robust methods for gene doping detection which
      could be used by the World Anti-Doping Agency to monitor athletes and would meet
      the requirements of a legally defensible test. Here we review the approaches and
      technologies which are being evaluated for the detection of gene doping, as well
      as for monitoring the efficacy of legitimate gene therapy, in relation to the
      detection target, the type of sample required for analysis and detection methods.
      We examine the accumulated knowledge on responses of the body, at both cellular
      and systemic levels, to gene transfer and evaluate strategies for gene doping
      detection based on current knowledge of gene technology, immunology,
      transcriptomics, proteomics, biochemistry and physiology.

PMID- 18081215
TI  - Positive predictive value of computerized records for major congenital
      malformations.
AB  - PURPOSE: To assess the positive predictive value of computerized records in a
      linked database of vital records and infant claims, with medical record
      confirmation to detect congenital malformations in a Medicaid population.
      METHODS: Study subjects were selected from cases identified for three studies of
      congenital malformations in the Tennessee Medicaid (TennCare) population
      including 173 827 (studies 1 and 2) and 519 465 (study 3) mother/infant pairs.
      Possible malformations were identified from computerized databases of birth
      certificates linked with maternal and infant claims. Medical records were
      reviewed for all possible congenital malformations and positive predictive values
      were calculated for each data source and for each malformation. RESULTS: Among
      1430 potential congenital malformations identified from either birth certificates
      or inpatient claims, 67.7% were confirmed by medical record review. The positive
      predictive value varied considerably depending on the data source and the organ
      system. For example, cardiac defects had a very low positive predictive value
      when identified from birth certificates, and somewhat higher positive predictive
      value when identified from inpatient claims. Orofacial defects had 90.9% positive
      predictive value from birth certificates and inpatient claims. Requiring evidence
      of a diagnostic or therapeutic procedure increased the positive predictive value
      to >90% for specific defects, but substantially reduced the number of included
      cases. CONCLUSIONS: Depending on the defect, computerized claims data linked to
      vital records offer opportunities for identifying birth defects in populations of
      vulnerable persons. However, for many defects, medical record confirmation is
      likely to be required to provide valid identification of malformation occurrence.

PMID- 18081216
TI  - What's wrong with sentinel node mapping in colon cancer?
AB  - Despite near-universal embrace of the concept and clinical relevance of lymphatic
      mapping for sentinel node identification and analysis for cancers of the breast
      and integument, the same technique has struggled to a find a role in
      gastrointestinal cancers in general and, perhaps, in colon cancer in particular.
      Despite many studies demonstrating its feasibility in malignancies of the large
      bowel, concern is continually aroused by the variable and often unacceptably low
      sensitivity rates. Additionally, many confess uncertainty as to what benefit it
      could ever confer to patients even if it were proven sufficiently accurate given
      that standard surgical resection incorporates mesenteric resection anyway.
      However, the huge impact sentinel node mapping has had on clinical practice in
      certain cancers means that each of these aspects merit careful reconsideration,
      from very first principles.

PMID- 18081218
TI  - Role of endoscopic retrograde cholangiopancreatography in acute pancreatitis.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is a useful tool in the
      evaluation and management of acute pancreatitis. This review will focus on the
      role of ERCP in specific causes of acute pancreatitis, including microlithiasis
      and gallstone disease, pancreas divisum, Sphincter of Oddi dysfunction, tumors of
      the pancreaticobiliary tract, pancreatic pseudocysts, and pancreatic duct injury.
      Indications for endoscopic techniques such as biliary and pancreatic
      sphincterotomy, stenting, stricture dilation, treatment of duct leaks, drainage
      of fluid collections and stone extraction will also be discussed in this review.
      With the advent of less invasive and safer diagnostic modalities including
      endoscopic ultrasound (EUS) and magnetic retrograde cholangiopancreatography
      (MRCP), ERCP is appropriately becoming a therapeutic rather than diagnostic tool
      in the management of acute pancreatitis and its complications.

PMID- 18081217
TI  - Review of idiopathic pancreatitis.
AB  - Recent advances in understanding of pancreatitis and advances in technology have
      uncovered the veils of idiopathic pancreatitis to a point where a thorough
      history and judicious use of diagnostic techniques elucidate the cause in over
      80% of cases. This review examines the multitude of etiologies of what were once
      labeled idiopathic pancreatitis and provides the current evidence on each. This
      review begins with a background review of the current epidemiology of idiopathic
      pancreatitis prior to discussion of various etiologies. Etiologies of
      medications, infections, toxins, autoimmune disorders, vascular causes, and
      anatomic and functional causes are explored in detail. We conclude with
      management of true idiopathic pancreatitis and a summary of the various etiologic
      agents. Throughout this review, areas of controversies are highlighted.

PMID- 18081219
TI  - Utility of endoscopic ultrasound in pancreatitis: a review.
AB  - The close proximity of the endoscopic ultrasound probe to the pancreas results in
      superior spatial resolution compared to CT scan and MRI. In addition, endoscopic
      ultrasound (EUS) is a minimally invasive procedure that does not share the
      relatively high complication rate of ERCP. Due to these advantages, EUS has
      evolved into an important technique to assess pancreatobiliary disease. This
      review will discuss the role of EUS in patients with pancreatitis. The
      indications can be divided into acute pancreatitis and chronic pancreatitis. In
      acute pancreatitis, EUS is used to determine the etiology; in suspected chronic
      pancreatitis it is helpful to establish the diagnosis. Lastly, this review will
      discuss biliary pancreatitis with suspicion for persistent choledocholithiasis.

PMID- 18081220
TI  - Autoimmune pancreatitis: a review.
AB  - Autoimmune pancreatitis has emerged over the last 40 years from a proposed
      concept to a well established and recognized entity. As an efficient mimicker of
      pancreatic carcinoma, its early and appropriate recognition are crucial. With
      mounting understanding of its pathogenesis and natural history, significant
      advances have been made in the diagnosis of autoimmune pancreatitis. The
      characteristic laboratory features and imaging seen in autoimmune pancreatitis
      are reviewed along with some of the proposed diagnostic criteria and treatment
      algorithms.

PMID- 18081222
TI  - Pancreatic endocrine and exocrine changes in celiac disease.
AB  - Although there is a great deal of information on celiac disease and associated
      involvement of other non-intestinal sites, data on concomitant changes in the
      structure and function of the pancreas is limited. The present review critically
      examines pancreatic endocrine changes that have been well documented in the
      literature, including insulin-dependent diabetes mellitus. Pancreatic exocrine
      alterations may also occur, and if severe, marked malnutrition with pancreatic
      failure and ductal calcification have been observed. Finally, other pancreatic
      disorders have been recorded with celiac disease.

PMID- 18081221
TI  - Sphincter of Oddi dysfunction and pancreatitis.
AB  - Sphincter of Oddi dysfunction (SOD) is a term used to describe a group of
      heterogenous pain syndromes caused by abnormalities in sphincter contractility.
      Biliary and pancreatic SOD are each sub-classified as type I, II or III,
      according to the Milwaukee classification. SOD appears to carry an increased risk
      of acute pancreatitis as well as rates of post ERCP pancreatitis of over 30%.
      Various mechanisms have been postulated but the exact role of SOD in the
      pathophysiology of acute pancreatitis is unknown. There is also an association
      between SOD and chronic pancreatitis but it is still unclear if this is a cause
      or effect relationship. Management of SOD is aimed at sphincter ablation, usually
      by endoscopic sphincterotomy (ES). Patients with type I SOD will benefit from ES
      in 55%-95% of cases. Sphincter of Oddi manometry is not necessary before ES in
      type I SOD. For patients with types II and III the benefit of ES is lower. These
      patients should be more thoroughly evaluated before performing ES. Some
      researchers have found that manometry and ablation of both the biliary and
      pancreatic sphincters is required to adequately assess and treat SOD. In
      pancreatic SOD up to 88% of patients will benefit from sphincterotomy. Therefore,
      there have been calls from some quarters for the current classification system to
      be scrapped in favour of an overall system encompassing both biliary and
      pancreatic types. Future work should be aimed at understanding the mechanisms
      underlying the relationship between SOD and pancreatitis and identifying patient
      factors that will help predict benefit from endoscopic therapy.

PMID- 18081223
TI  - Transplantation for the treatment of type 1 diabetes.
AB  - Transplantation of pancreatic tissue, as either the intact whole pancreas or
      isolated pancreatic islets has become a clinical option to be considered in the
      treatment of patients with type 1 insulin-dependant diabetes mellitus. A
      successful whole pancreas or islet transplant offers the advantages of attaining
      normal or near normal blood glucose control and normal hemoglobin A1c levels
      without the risks of severe hypoglycemia associate with intensive insulin
      therapy. Both forms of transplants are also effective at eliminating the
      occurrence of significant hypoglycemic events (even with only partial islet
      function evident). Whereas whole pancreas transplantation has also been shown to
      be very effective at maintaining a euglycemic state over a sustained period of
      time, thus providing an opportunity for a recipient to benefit from improvement
      of their blood glucose control, it is associated with a significant risk of
      surgical and post-operative complications. Islet transplantation is attractive as
      a less invasive alternative to whole pancreas transplant and offers the future
      promise of immunosuppression-free transplantation through pre-transplant culture.
      Islet transplantation however, may not always achieve the sustained level of
      tight glucose control necessary for reducing the risk of secondary diabetic
      complications and exposes the patient to the adverse effects of
      immunosuppression. Although recent advances have led to an increased rate of
      obtaining insulin-independence following islet transplantation, further
      developments are needed to improve the long-term viability and function of the
      graft to maintain improved glucose control over time.

PMID- 18081224
TI  - Evaluation of quantitative contrast harmonic imaging to assess malignancy of
      liver tumors: a prospective controlled two-center study.
AB  - AIM: To establish the extent to which contrast enhancement with SonoVue in
      combination with quantitative evaluation of contrast-medium dynamics facilitates
      the detection of hepatic tumors. METHODS: One hundred patients with
      histologically confirmed malignant or benign hepatic tumor (maximum size 5 cm)
      were analyzed. Contrast-enhanced ultrasound (bolus injection 2.5 mL SonoVue) was
      carried out with intermittent breath-holding technique using a multifrequency
      transducer (2.5-4 MHz). Native vascularization was analyzed with power Doppler.
      The contrast-enhanced dynamic ultrasound investigation was carried out with
      contrast harmonic imaging in true detection mode during the arterial, portal
      venous and late phases. Mechanical index was set at 0.15. Perfusion analysis was
      performed by post-processing of the raw data [time intensity curve (TIC)
      analysis]. The cut-off of the gray value differences between tumor and normal
      liver tissue was established using Receiver Operating Characteristic (ROC)
      analysis 64-line multi-slice computed tomography served as reference method in
      all cases. Magnetic resonance tomography was used additionally in 19 cases.
      RESULTS: One hundred patients with 59 malignant (43 colon, 5 breast, 2 endocrine
      metastases, 7 hepatocellular carcinomas and 2 kidney cancers) and 41 benign (15
      hemangiomas, 7 focal nodular hyperplasias, 5 complicated cysts, 2 abscesses and
      12 circumscribed fatty changes) tumors were included. The late venous phase
      proved to be the most sensitive for classification of the tumor type. Fifty-eight
      of the 59 malignant tumors were classified as true positive, and one as false
      negative. This resulted in a sensitivity of 98.3%. Of the 41 benign tumors, 37
      were classified as true negative and 4 as false negative, which corresponds to a
      specificity of 90.2%. Altogether, 95.0% of the diagnoses were classified as
      correct on the basis of the histological classification. No investigator
      dependency (P = 0.23) was noted. CONCLUSION: The results show the possibility of
      accurate prediction of malignancy of hepatic tumors with a positive prognostic
      value of 93.5% using advanced contrast-enhanced ultrasound. Contrast enhancement
      with SonoVue in combination with quantitative evaluation of contrast-medium
      dynamics is a valuable tool to discriminate hepatic tumors.

PMID- 18081225
TI  - Analysis of the expression of coxsackievirus and adenovirus receptor in five
      colon cancer cell lines.
AB  - AIM: To investigate the expression of coxsackievirus and adenovirus receptor
      (CAR) and adenovirus-mediated reporter gene transfer in five human colon cancer
      cell lines. METHODS: Expression of CAR-specific mRNA and protein was analyzed by
      reverse transcriptase polymerase chain reaction and Western blotting,
      respectively. Adenovirus-based gene delivery was evaluated by infection of cells
      with adenoviral vector carrying the green fluorescent protein (GFP) gene.
      RESULTS: All the colon cancer cell lines examined (HT29, LS180, SW480, SW948 and
      SW1116) expressed CAR full-length mRNA and an alternatively-spliced variant that
      lacks the transmembrane coding exon. All cell lines were detected as CAR-positive
      by Western blot analysis. Further, all cells we examined were efficiently
      infected with adenoviral vector-GFP. CONCLUSION: The data indicated that the five
      colon cancer cell lines tested expressed adenovirus primary receptor and could be
      efficiently infected by adenoviral vectors. Therefore, these cell lines will be
      useful for adenovirus-based gene transfer and research.

PMID- 18081226
TI  - Probiotic bacteria change Escherichia coli-induced gene expression in cultured
      colonocytes: Implications in intestinal pathophysiology.
AB  - AIM: To investigate the change in eukaryotic gene expression profile in Caco-2
      cells after infection with strains of Escherichia coli and commensal probiotic
      bacteria. METHODS: A 19,200 gene/expressed sequence tag gene chip was used to
      examine expression of genes after infection of Caco-2 cells with strains of
      normal flora E. coli, Lactobacillus plantarum, and a combination of the two.
      RESULTS: The cDNA microarray revealed up-regulation of 155 and down-regulation of
      177 genes by E. coli. L. plantarum up-regulated 45 and down-regulated 36 genes.
      During mixed infection, 27 genes were up-regulated and 59 were down-regulated,
      with nullification of stimulatory/inhibitory effects on most of the genes.
      Expression of several new genes was noted in this group. CONCLUSION: The
      commensal bacterial strains used in this study induced the expression of a large
      number of genes in colonocyte-like cultured cells and changed the expression of
      several genes involved in important cellular processes such as regulation of
      transcription, protein biosynthesis, metabolism, cell adhesion, ubiquitination,
      and apoptosis. Such changes induced by the presence of probiotic bacteria may
      shape the physiologic and pathologic responses they trigger in the host.

PMID- 18081227
TI  - Inflammatory cytokines promote inducible nitric oxide synthase-mediated DNA
      damage in hamster gallbladder epithelial cells.
AB  - AIM: To investigate the link between chronic biliary inflammation and
      carcinogenesis using hamster gallbladder epithelial cells. METHODS: Gallbladder
      epithelial cells were isolated from hamsters and cultured with a mixture of
      inflammatory cytokines including interleukin-1beta, interferon-gamma, and tumor
      necrosis factor-alpha. Inducible nitric oxide synthase (iNOS) expression, nitric
      oxide (NO) generation, and DNA damage were evaluated. RESULTS: NO generation was
      increased significantly following cytokine stimulation, and suppressed by an iNOS
      inhibitor. iNOS mRNA expression was demonstrated in the gallbladder epithelial
      cells during exposure to inflammatory cytokines. Furthermore, NO-dependent DNA
      damage, estimated by the comet assay, was significantly increased by cytokines,
      and decreased to control levels by an iNOS inhibitor. CONCLUSION: Cytokine
      stimulation induced iNOS expression and NO generation in normal hamster
      gallbladder epithelial cells, which was sufficient to cause DNA damage. These
      results indicate that NO-mediated genotoxicity induced by inflammatory cytokines
      through activation of iNOS may be involved in the process of biliary
      carcinogenesis in response to chronic inflammation of the biliary tree.

PMID- 18081228
TI  - Intestinal endotoxemia plays a central role in development of hepatopulmonary
      syndrome in a cirrhotic rat model induced by multiple pathogenic factors.
AB  - AIM: To characterize the correlation between severity of hepatopulmonary syndrome
      (HPS) and degree of hepatic dysfunction, and to explore how intestinal
      endotoxemia (IETM) affects the development of HPS in cirrhotic rats. METHODS:
      Male Wister rats were fed with a diet containing maize flour, lard, cholesterol,
      and alcohol and injected subcutaneously with CCl(4) oil solution every two days
      for 8 wk to induce typical cirrhosis and development of HPS. The animals were
      also given a nitric oxide (NO) production inhibitor, N(omega)-nitro-L-arginine
      methyl ester (L-NAME) intraperitoneally, and an iNOS inhibitor, aminoguanidine
      hydrochloride (AG) via gavage daily from the end of the 4th wk to the end of the
      6th or 8th wk, or a HO-1 inhibitor, zinc protoporphyrin (ZnPP) intraperitoneally
      12 h prior to killing. Blood, liver and lung tissues were sampled. RESULTS:
      Histological deterioration of the lung paralleled to that of the liver in the
      cirrhotic rats. The number of pulmonary capillaries was progressively increased
      from 6.1 +/- 1.1 (count/filed) at the 4th wk to 14.5 +/- 2.4 (count/filed) at the
      8th wk in the cirrhotic rats. Increased pulmonary capillaries were associated
      with increased blood levels of lipopolysaccharide (LPS) (0.31 +/- 0.08 EU/mL vs
      control 0.09 +/- 0.03 EU/mL), alanine transferase (ALT, 219.1 +/- 17.4 U/L vs
      control 5.9 +/- 2.2 U/L) and portal vein pressure. Compared with normal control
      animals, the number of total cells in bronchoalveolar lavage fluid (BALF) of the
      cirrhotic rats at the 8th wk was not changed, but the number of macrophages and
      the ratio of macrophages to total cells were increased by nearly 2-fold, protein
      expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide
      synthase (eNOS) started to increase significantly at the 4th wk, and reached its
      peak at the 8th wk in the lung of cirrhotic rats. The increase of iNOS expression
      appeared to be quicker than that of eNOS. NO(2)(-)/NO(3)(-) was also increased,
      which was correlated to the increase of iNOS (r = 0.7699, P < 0.0001) and eNOS (r
      = 0.5829, P < 0.002). mRNA expression of eNOS and iNOS was highly consistent with
      their protein expression. CONCLUSION: Progression and severity of HPS as
      indicated by both increased pulmonary capillaries and histological changes are
      closely associated with LPS levels and progression of hepatic dysfunction as
      indicated by increased levels of ALT and portal vein pressure. Intestinal
      endotoxemia plays a central role in the development of HPS in the cirrhotic rat
      model by inducing NO and/or CO.

PMID- 18081229
TI  - Two distinct pathways of p16 gene inactivation in gallbladder cancer.
AB  - AIM: To examine the mechanism of inactivation of the p16 gene in gallbladder
      cancer, and to investigate p16 alterations and their correlation with
      clinicopathological features. METHODS: Specimens were collected surgically from
      51 patients with gallbladder cancer. We evaluated the status of protein
      expression, loss of heterozygosity (LOH), homozygous deletion and promoter
      hypermethylation using immunohistochemistry, microsatellite analysis,
      quantitative real-time polymerase chain reaction (PCR) and methylation-specific
      PCR, respectively. In addition, mutations were examined by direct DNA sequencing.
      RESULTS: Homozygous deletions of the p16 gene exon2, LOH at 9p21-22, p16 promoter
      hypermethylation, and loss of p16 protein expression were detected in 26.0%
      (13/50), 56.9% (29/51), 72.5% (37/51) and 62.7% (32/51), respectively. No
      mutations were found. LOH at 9p21 correlated with the loss of p16 protein
      expression (P < 0.05). Homozygous deletion of the p16 gene, a combination LOH and
      promoter hypermethylation, and multiple LOH at 9p21 were significantly correlated
      with the loss of p16 protein expression (P < 0.05). LOH at 9p21 and promoter
      hypermethylation of the p16 gene were detected in 15.4% (2/13) and 92.3% (12/13)
      of the tumors with homozygous deletion of the p16 gene, respectively. P16
      alterations were not associated with clinicopathological features. CONCLUSION:
      Our results suggest that LOH and homozygous deletion may be two distinct pathways
      in the inactivation of the p16 gene. Homozygous deletion, a combination of LOH
      and promoter hypermethylation, and multiple LOH are major mechanisms of p16
      inactivation in gallbladder cancer.

PMID- 18081230
TI  - Left-sided gallbladder: its clinical significance and imaging presentations.
AB  - AIM: To assess the importance of preoperative diagnosis and presentation of left
      sided gallbladder using ultrasound (US), CT and angiography. METHODS:
      Retrospective review of 1482 patients who underwent enhanced CT scanning was
      performed. Left-sided gallbladder was diagnosed if a right-sided ligamentum teres
      was present. The image presentations on US, CT and angiography were also
      reviewed. RESULTS: Left-sided gallbladder was diagnosed in nine patients. The
      associated abnormalities on CT imaging included portal vein anomalies, absence of
      umbilical portion of the portal vein in the left lobe of the liver, club-shaped
      portal vein in the right lobe of the liver, and difficulty in identifying segment
      IV. Angiography in six of nine patients demonstrated abnormal portal venous
      system (trifurcation type in four of six patients). The main hepatic arteries
      followed the portal veins in all six patients. The segment IV artery was
      identified in four of six patients using angiography, although segment IV was
      difficult to define on CT imaging. Hepatectomy was performed in three patients
      with concomitant liver tumor and the diagnosis of left-sided gallbladder was
      confirmed intraoperatively. CONCLUSION: Left-sided gallbladder is an important
      clinical entity in hepatectomy due to its associated portal venous and biliary
      anomalies. It should be considered in US, CT and angiography images that
      demonstrate no definite segment IV, absence of umbilical portion of the portal
      vein in the left lobe, and club-shaped right anterior portal vein.

PMID- 18081231
TI  - New method for long-term monitoring of intragastric pH.
AB  - AIM: Consecutive monitoring of intragastric pH using the Bravo capsule. METHODS:
      We put threads through a Bravo capsule and then affixed it to the gastric wall by
      endoscopic hemoclipping in seven subjects. Study data were uploaded to a computer
      via Datalink every 48 h. In this way, repeated monitoring of intragastric pH was
      undertaken. RESULTS: All subjects were able to monitor gastric pH over a 1-wk
      period, and five for > 2 wk. No complications were encountered during the
      monitoring. After pH monitoring, we safely retrieved the capsule endoscopically.
      CONCLUSION: Clipping a Bravo capsule onto the gastric wall enabled long-term
      intragastric pH monitoring. This is a methodological report of pH monitoring over
      a period of > 2 wk.

PMID- 18081232
TI  - Personality factors and profiles in variants of irritable bowel syndrome.
AB  - AIM: To study the association between irritable bowel syndrome (IBS) variants
      (constipation, diarrhea, or both) and personality traits in non-psychiatric
      patients. METHODS: IBS was diagnosed using the Rome II diagnostic criteria after
      exclusion of organic bowel pathology. The entry of each patient was confirmed
      following a psychiatric interview. Personality traits and the score of each
      factor were evaluated using the NEO Five Factor Inventory. RESULTS: One hundred
      and fifty patients were studied. The mean age (+/- SD) was 33.4 (+/- 11.0) year
      (62% female). Subjects scored higher in neuroticism (26.25 +/- 7.80 vs 22.92 +/-
      9.54, P < 0.0005), openness (26.25 +/- 5.22 vs 27.94 +/- 4.87, P < 0.0005) and
      conscientiousness (32.90 +/- 7.80 vs 31.62 +/- 5.64, P < 0.01) compared to our
      general population derived from universities of Iran. Our studied population
      consisted of 71 patients with Diarrhea dominant-IBS, 33 with Constipation
      dominant-IBS and 46 with Altering type-IBS. Scores of conscientiousness and
      neuroticism were significantly higher in C-IBS compared to D-IBS and A-IBS (35.79
      +/- 5.65 vs 31.95 +/- 6.80, P = 0.035 and 31.97 +/- 9.87, P = 0.043,
      respectively). Conscientiousness was the highest dimension of personality in each
      of the variants. Patients with C-IBS had almost similar personality profiles,
      composed of higher scores for neuroticism and conscientiousness, with low levels
      of agreeableness, openness and extraversion that were close to those of the
      general population. CONCLUSION: Differences were observed between IBS patients
      and the general population, as well as between IBS subtypes, in terms of
      personality factors. Patients with constipation-predominant IBS showed similar
      personality profiles. Patients with each subtype of IBS may benefit from
      psychological interventions, which can be focused considering the characteristics
      of each subtype.

PMID- 18081233
TI  - Prevalence of fatty liver disease and its risk factors in the population of South
      China.
AB  - AIM: To investigate the population-based prevalence of fatty liver disease (FLD)
      and its risk factors in Guangdong Province, China. METHODS: A cross-sectional
      survey with multiple-stage stratified cluster and random sampling of inhabitants
      over 7-year-old was performed in 6 urban and rural areas of Guangdong Province,
      China. Questionnaires, designed by co-working of epidemiologists and
      hepatologists, included demographic characteristics, current medication use,
      medical history and health-relevant behaviors, i.e. alcohol consumption, smoking
      habits, dietary habits and physical activities. Anthropometric measurements,
      biochemical tests and abdominal ultrasonography were carried out. RESULTS: Among
      the 3543 subjects, 609 (17.2%) were diagnosed having FLD (18.0% males, 16.7%
      females, P > 0.05). Among them, the prevalence of confirmed alcoholic liver
      disease (ALD), suspected ALD and nonalcoholic fatty liver disease (NAFLD) were
      0.4%, 1.8%, and 15.0%, respectively. The prevalence rate (23.0%) was
      significantly higher in urban areas than (12.9%) in rural areas. After adjustment
      for age, gender and residency, the standardized prevalence of FLD in adults was
      14.5%. Among them, confirmed ALD, suspected ALD and NAFLD were 0.5%, 2.3%, and
      11.7%, respectively, in adults and 1.3% (all NAFLD) in children at the age of 7
      18 years. The overall prevalence of FLD increased with age in both genders to the
      peak of 27.4% in the group of subjects at the age of 60-70 years. The prevalence
      rate was significantly higher in men than in women under the age of 50 years
      (22.4% vs 7.1%, P < 0.001). However, the opposite phenomenon was found over the
      age of 50 years (20.6% vs 27.6%, P < 0.05). Multivariate and logistic regression
      analysis indicated that male gender, urban residency, low education, high blood
      pressure, body mass index, waist circumference, waist to hip ratio, serum
      triglyceride and glucose levels were the risk factors for FLD. CONCLUSION: FLD,
      especially NAFLD, is prevalent in South China. There are many risk factors for
      FLD.

PMID- 18081234
TI  - Antitumor and antiangiogenic activities of anti-vascular endothelial growth
      factor hairpin ribozyme in human hepatocellular carcinoma cell cultures and
      xenografts.
AB  - AIM: To study the effectiveness and mechanisms of anti- human vascular
      endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis, oncogenicity
      and tumor growth in a hepatocarcinoma cell line and a xenografted model. METHODS:
      The artificial anti-hVEGF hairpin ribozyme was transfected into hepatocarcinoma
      cell line SMMC-7,721 and, subsequently, polymerase chain reaction (PCR) and
      reverse transcription polymerase chain reaction (RT-PCR) were performed to
      confirm the ribozyme gene integration and transcription. To determine the effects
      of ribozyme ,VEGF expression was detected by semiquantitative RT-PCR and enzyme
      liked immunosorbent assay (ELISA). MTT assay was carried out to measure the cell
      proliferation. Furthermore,the transfected and control cells were inoculated into
      nude mice respectively, the growth of cells in nude mice and angiogenesis were
      observed. RESULTS: VEGF expression was down-regulated sharply by ribozyme in
      transfected SMMC-7,721 cells and xenografted tumor. Compared to the control
      group, the transfected cells grew slower in cell cultures and xenografts, and the
      xenograft formation was delayed as well. In addition, the microvessel density of
      the xenografted tumor was obviously declined in the transfected group. As
      demonstrated by microscopy,reduction of VEGF production induced by ribozyme
      resulted in a significantly higher cell differentiation and less proliferation
      vigor in xenografted tumor. CONCLUSION: Anti-hVEGF hairpin ribozyme can
      effectively inhibit VEGF expression and growth of hepatocarcinoma in vitro and in
      vivo. VEGF is functionally related to cell proliferation, differentiation and
      tumori-genesis in hepatocarcinoma.

PMID- 18081235
TI  - Complete pathological response following down-staging chemoradiation in locally
      advanced pancreatic cancer: challenging the boundaries.
AB  - Pancreatic cancer is an aggressive malignancy, relatively resistant to
      chemotherapy and radiotherapy, which usually presents late. Disease specific
      mortality approaches unity despite advances in adjuvant therapy. We present the
      first reported case of complete pathological response following neoadjuvant
      therapy in a locally advanced pancreatic adenocarcinoma.

PMID- 18081236
TI  - Metastatic hepatocellular carcinoma of the external auditory canal.
AB  - This report describes a rare case of metastatic hepatocellular carcinoma (HCC)
      presenting a huge mass in the left external auditory canal (EAC). The patient was
      a 55-year-old man with hepatitis B virus-related HCC. He presented to our
      department with a three-month history of increasing left otalgia, and hearing
      loss with recent fresh aural bleeding. Histopathologic examination indicated that
      the tumor was secondary to HCC. Although external irradiation was not effective,
      the tumor was treated with surgical debulking and high dose rate 192 Ir remote
      afterloading system (RALS) for postoperative intracavitary irradiation. A review
      of the literature revealed only five other cases of HCC metastasis to the
      temporal bone, all of which mainly metastasized in the internal acoustic meatus.
      The present case is the first report of HCC metastasis to the EAC.

PMID- 18081237
TI  - Decompensated porto-pulmonary hypertension in a cirrhotic patient with thrombosis
      of portocaval shunt.
AB  - We report a case of decompensated porto-pulmonary hypertension closely associated
      with the development of intra-portocaval shunt thrombosis. A woman with Laennec's
      cirrhosis was hospitalized because of severe dyspnea and edema. She underwent
      surgical portocaval anastomosis ten years ago. Imaging studies showed massive
      intra-shunt thrombosis, portal hypertension, ascites, pleuro-pericardial
      effusions and enlargement of right cardiac cavities. Cardiac catheterization
      allowed to rule out coronary and left-sided heart abnormalities and led to the
      diagnosis of pre-capillary pulmonary hypertension. Antithrombotic treatment with
      low molecular weight heparin was instituted. The management also included ACE
      inhibitors, spironolactone, low-salt diet and lactulose. The patient was
      discharged and three months later we observed the disappearance of edema, ascites
      and pleuro-pericardial effusions, a marked body weight reduction and improved
      dyspnea and liver function tests. A possible link between the development of
      intra-shunt thrombosis and clinical decompensation in our patient was
      hypothesized. In fact, it has been demonstrated that the increased portal
      pressure, caused by occlusion of portosystemic shunt, reduces renal plasma flow
      and increases systemic endothelin-1 concentration. In our patient the
      disappearance of edematous state and improved dyspnea observed after
      recanalization of the shunt strongly support this hypothesis.

PMID- 18081238
TI  - Malignant fibrous histiocytoma presenting as hemoperitoneum mimicking
      hepatocellular carcinoma rupture.
AB  - Malignant fibrous histiocytoma (MFH) is a pleomorphic mesenchynal sarcoma. It is
      uncommonly arises primarily from the intra-peritoneal cavity. Primary peritoneal
      MFH with tumor bleeding and rupture is rare. We describe the imaging features of
      a 70-year-old patient presenting with ruptured hemorrhagic peritoneal MFH at
      subhepatic area, accompanied by massive hemoperitoneum, mimicking a ruptured
      pedunculated hepatocellular carcinoma. Computed tomography (CT) revealed a large
      heterogeneous enhanced subhepatic mass with adjacent liver, gallbladder and colon
      invasion. Tumor hemorrhage and rupture complicated with peritoneal seeding and
      massive bloody ascites were also detected. Angiography showed a hypervascular
      tumor fed by enlarged right hepatic arteries, cystic artery and omental branches
      of gastroepiploic artery. The patient underwent laparotomy for tumor resection,
      but the tumor recurred one month after operation. To our knowledge, the CT
      appearance of ruptured intraperitoneal MFH complicated by hemoperitoneum has not
      been previously described.

PMID- 18081239
TI  - Eosinophilic enteritis presenting as a rare cause for ileo-ileal intussusception.
AB  - Eosinophilic enteritis, a relatively rare entity, usually involves gastric antrum
      or proximal small bowel. Our case is rarer in its involvement of the distal small
      bowel and presents unusually as intussusception. The disease if diagnosed in the
      initial stages responds well to medical treatment but if associated with
      complications or misdiagnosed, surgical modality is the treatment of choice. In
      our case, the patient presented with acute intestinal obstruction due to
      intussusception and emergency laparotomy with ileoileal anastomosis was done.
      Histopathology confirmed the diagnosis as eosinophilic enteritis. This case with
      such a presentation is discussed here.

PMID- 18081240
TI  - Migrated endoclip and stone formation after cholecystectomy: a new danger of
      acute pancreatitis.
AB  - Endoclip migration into the common bile duct following laparoscopic
      cholecystectomy (LC) is an extremely rare complication. Migrated endoclip into
      the common bile duct can cause obstruction, serve as a nidus for stone formation,
      and cause cholangitis. We report a case of obstructive jaundice and acute biliary
      pancreatitis due to choledocholithiasis caused by a migrated endoclip 6 mo after
      LC. The patient underwent early endoscopic retrograde cholangiopancreatography
      (ERCP) with endoscopic sphincterotomy and stone extraction.

PMID- 18081241
TI  - Applications of mesenchymal stem cells labeled with Tat peptide conjugated
      quantum dots to cell tracking in mouse body.
AB  - Fluorescent quantum dots have great potential in cellular labeling and tracking.
      Here, PEG encapsulated CdSe/ZnS quantum dots have been conjugated with Tat
      peptide, and introduced into living mesenchymal stem cells. The Tat peptide
      conjugated quantum dots in mesenchymal stem cells were assessed by fluorescent
      microscopy, laser confocal microscope and. flow cytometry. The result shows that
      Tat peptide conjugated quantum dots could enter mesenchymal stem cells
      efficiently. The Tat-quantum dots labeled stem cells were further injected into
      the tail veins of NOD/SCID beta2 M null mice, and the tissue distribution of
      these labeled cells in nude mice were examined with fluorescence microscope. The
      result shows that characteristic fluorescence of quantum dots was observed
      primarily in the liver, the lung and the spleen, with little or no quantum dots
      accumulation in the brain, the heart, or the kidney.

PMID- 18081242
TI  - Postsynthetic derivatization of fluorophores with alpha-sulfo-beta-alanine
      dipeptide linker. Application to the preparation of water-soluble cyanine and
      rhodamine dyes.
AB  - A straightforward method to enhance water solubility of fluorescent organic dyes
      (cyanines and rhodamines) by a postsynthetic chemical derivatization of their
      carboxylic acid functionality with an original disulfonated heterobifunctional
      linker is described. Significant water solubility enhancement is achieved without
      compromising either the photophysical properties (especially large molar
      extinction coefficients and high quantum yields) or bioconjugation efficiency of
      the parent non-water-soluble fluorophores. The results both demonstrate the
      strong potential of these new compounds as fluorescent labels for a broad range
      of biotechnology and biomedical applications and illustrate the utility of such
      an easy-to-handle water-solubizing group.

PMID- 18081243
TI  - What's driving false discovery rates?
AB  - The "Paris Guidelines" have begun the process of standardizing reporting for
      proteomics. New bioinformatics tools have improved the process for estimating
      error rates of peptide identifications. This perspective seeks to consider these
      advances in the context of proteomics' short history. As increasing numbers of
      proteomics papers come from biologists rather than technologists, developing
      consensus standards for estimating error will be increasingly necessary.
      Standardizing this assessment should be welcomed as a reflection of the growing
      impact of proteomic technologies.

PMID- 18081244
TI  - Data augmentation algorithms for detecting conserved domains in protein
      sequences: a comparative study.
AB  - Protein conserved domains are distinct units of molecular structure, usually
      associated with particular aspects of molecular function such as catalysis or
      binding. These conserved subsequences are often unobserved and thus in need of
      detection. Motif discovery methods can be used to find these unobserved domains
      given a set of sequences. This paper presents the data augmentation (DA)
      framework that unifies a suite of motif-finding algorithms through maximizing the
      same likelihood function by imputing the unobserved data. The data augmentation
      refers to those methods that formulate iterative optimization by exploiting the
      unobserved data. Two categories of maximum likelihood based motif-finding
      algorithms are illustrated under the DA framework. The first is the deterministic
      algorithms that are to maximize the likelihood function by performing an
      iteratively optimal local search in the alignment space. The second is the
      stochastic algorithms that are to iteratively draw motif location samples via
      Monte Carlo simulation and simultaneously keep track of the superior solution
      with the best likelihood. As a result, four DA motif discovery algorithms are
      described, evaluated, and compared by aligning real and simulated protein
      sequences.

PMID- 18081245
TI  - Enhanced membrane protein topology prediction using a hierarchical classification
      method and a new scoring function.
AB  - The prediction of transmembrane (TM) helix and topology provides important
      information about the structure and function of a membrane protein. Due to the
      experimental difficulties in obtaining a high-resolution model, computational
      methods are highly desirable. In this paper, we present a hierarchical
      classification method using support vector machines (SVMs) that integrates
      selected features by capturing the sequence-to-structure relationship and
      developing a new scoring function based on membrane protein folding. The proposed
      approach is evaluated on low- and high-resolution data sets with cross
      validation, and the topology (sidedness) prediction accuracy reaches as high as
      90%. Our method is also found to correctly predict both the location of TM
      helices and the topology for 69% of the low-resolution benchmark set. We also
      test our method for discrimination between soluble and membrane proteins and
      achieve very low overall false positive (0.5%) and false negative rates (0 to
      approximately 1.2%). Lastly, the analysis of the scoring function suggests that
      the topogeneses of single-spanning and multispanning TM proteins have different
      levels of complexity, and the consideration of interloop topogenic interactions
      for the latter is the key to achieving better predictions. This method can
      facilitate the annotation of membrane proteomes to extract useful structural and
      functional information. It is publicly available at http://bio
      cluster.iis.sinica.edu.tw/~bioapp/SVMtop.

PMID- 18081247
TI  - Identification of geranic acid, a tyrosinase inhibitor in lemongrass (Cymbopogon
      citratus).
AB  - Lemongrass is a popular Asian herb having a lemon-like flavor. Very recently,
      potent tyrosinase inhibitory activity has been found in lemongrass in addition to
      various biological activities reported in the literature. The aim of the present
      study is to identify the active compounds in the lemongrass. An assay-guided
      purification revealed that one of the active substances was geranic acid. Geranic
      acid has two stereoisomers, which are responsible for the trans and cis geometry
      on the conjugated double bond. Both isomers are present in the active ethyl
      acetate-soluble extract of the lemongrass, and their IC50 values were calculated
      to be 0.14 and 2.3 mM, respectively. The structure requirement of geranic acid
      for the potent tyrosinase inhibitory activity was investigated using geranic acid
      related compounds.

PMID- 18081246
TI  - Comparison of 1D and 2D NMR spectroscopy for metabolic profiling.
AB  - High-resolution, liquid state nuclear magnetic resonance (NMR) spectroscopy is a
      popular platform for metabolic profiling because the technique is nondestructive,
      quantitative, reproducible, and the spectra contain a wealth of biochemical
      information. Because of the large dynamic range of metabolite concentrations in
      biofluids, statistical analyses of one-dimensional (1D) proton NMR data tend to
      be biased toward selecting changes in more abundant metabolites. Although two
      dimensional (2D) proton-proton experiments can alleviate spectral crowding, they
      have been mainly used for structural determination. In this study, 2D total
      correlation spectroscopy NMR was used to compare the global metabolic profiles of
      urine obtained from wild-type and Abcc6-knockout mice. The 2D data were compared
      to an improved 1D experiment in which signal contributions from macromolecules
      and the urea peak have been spectroscopically removed for more accurate
      quantitation of low-abundance metabolites. Although statistical models from both
      1D and 2D data could differentiate samples acquired from the two groups of mice,
      only the 2D spectra allowed the characterization of statistically relevant
      changes in the low-abundance metabolites. While acquisition of the 2D data
      require more time, the data obtained resulted in a more meaningful and
      comprehensive metabolic profile, aided in metabolite identifications, and
      minimized ambiguities in peak assignments.

PMID- 18081248
TI  - Characterization of volatile aroma compounds in cooked black rice.
AB  - Black rice ( Oryza sativa L.), an aromatic specialty rice popular in Asia, has a
      unique flavor, the volatile chemistry of which has not been reported. The
      objectives of this research were to study volatile profiles of cooked black rice
      and to characterize the odor-active compounds. Thirty-five volatile compounds
      were identified by gas chromatography-mass spectrometry using a dynamic headspace
      system with Tenax trapping. Aldehydes and aromatics were quantitatively in the
      greatest abundance, accounting for 80.1% of total relative concentration of
      volatiles. The concentration of 2-acetyl-1-pyrroline (2-AP) was high, exceeded
      only by hexanal, nonanal, and 2-pentylfuran. A total of 25 odor-active compounds,
      determined by gas chromatography-olfactometry, were applied to principal
      component analysis, demonstrating significant differences between a black and a
      traditional white rice cultivar in terms of aroma and explaining 93.0% of the
      total variation. 2-AP, guaiacol, indole, and p-xylene largely influenced the
      difference between the aroma in cooked black and white rice. 2-AP and guaiacol
      were major contributors to the unique character of black rice based on odor
      thresholds, relative concentrations, and olfactometry.

PMID- 18081249
TI  - 1H NMR quantitative determination of photosynthetic pigments from green beans
      (Phaseolus vulgaris L.).
AB  - Using 1H nuclear magnetic resonance spectroscopy (1D and 2D), the two types of
      photosynthetic pigments (chlorophylls, their derivatives, and carotenoids) of
      "green beans" (immature pods of Phaseolus vulgaris L.) were analyzed. Compared to
      other analytical methods (light spectroscopy or chromatography), 1H NMR
      spectroscopy is a fast analytical way that provides more information on
      chlorophyll derivatives (allomers and epimers) than ultraviolet-visible
      spectroscopy. Moreover, it gives a large amount of data without prior
      chromatographic separation.

PMID- 18081250
TI  - Macroscopic DNA helices.
AB  - Presently there is great interest in the construction of nanostructures from DNA
      fragments. Here we report the preparation of much larger helical textures with
      different shapes from pure DNA fragments. We have observed them while preparing
      crystals of the dodecamer d(AAAAAATTTTTT), which only contains adenine and
      thymine. Noncoding regions of the genome are always rich in these two bases. We
      have found a strong influence of ions either monovalent or divalent, with which
      different crystalline structures are found. All of them contain long helical
      stacks of duplexes in the unit cell. The most remarkable structures are
      macroscopic helices with diameters and pitch in the range of 20-40 microm. Thus,
      pure DNA oligonucleotides may form a hierarchy of helical structures, going from
      the B-form double helix (pitch, p = 33 A) to helical stacks of duplexes (p
      approximately 900 A), and to macroscopic helices (p approximately 300,000 A).
      These different levels of organization are reminiscent of the different levels of
      organization of DNA in eukaryotic chromosomes.

PMID- 18081251
TI  - Composition and distribution of carrabiose moieties in hybrid kappa-/iota
      carrageenans using carrageenases.
AB  - Hybrid kappa/iota-carrageeans extracted from Gigartina skottsbergii,
      Chondracanthus chamissoi, and Chondrus crispus were incubated with
      Pseudoalteromonas carrageenovora kappa-carrageenase and Alteromonas fortis iota
      carrageenase. The degradation products as well as the resistant fraction were
      fully characterized by chromatography, NMR, and mass spectrometry. The low
      percentage of degradation observed after treatment by the iota-carrageenase
      suggests that long segments of iota-carrabiose or block of iota-carrageenan are
      low in abundance. The degradation products of the kappa-carrageenase allow
      discriminating three modes of kappa-carrabiose distribution: blocks of kappa
      carrabiose, kappa-carrabiose rich fraction containing iota-carrabiose units
      probably randomly distributed, and iota-carrabiose rich fraction which
      corresponds to the resistant fraction. The proportions of each fraction were
      related to the botanical origin as well as the place of growth of the seaweed.

PMID- 18081252
TI  - Self-assembled micelles of biodegradable triblock copolymers based on poly(ethyl
      ethylene phosphate) and poly(-caprolactone) as drug carriers.
AB  - A series of novel amphiphilic triblock copolymers of poly(ethyl ethylene
      phosphate) and poly(-caprolactone) (PEEP-PCL-PEEP) with various PEEP and PCL
      block lengths were synthesized and characterized. These triblock copolymers
      formed micelles composed of a hydrophobic core of poly(-caprolactone) (PCL) and a
      hydrophilic shell of poly(ethyl ethylene phosphate) (PEEP) in aqueous solution.
      The micelle morphology was spherical, determined by transmission electron
      microscopy. It was found that the size and critical micelle concentration values
      of the micelles depended on both hydrophobic PCL block length and PEEP
      hydrophilic block length. The in vitro degradation characteristics of the
      triblock copolymers were investigated in micellar form, showing that these
      copolymers were completely biodegradable under enzymatic catalysis of Pseudomonas
      lipase and phosphodiesterase I. These triblock copolymers were used for
      paclitaxel (PTX) encapsulation to demonstrate the potential in drug delivery. PTX
      was successfully loaded into the micelles, and the in vitro release profile was
      found to be correlative to the polymer composition. These biodegradable triblock
      copolymer micelles are potential as novel carriers for hydrophobic drug delivery.

PMID- 18081253
TI  - Macroscopic hydrogels by self-assembly of oligolactate-grafted dextran
      microspheres.
AB  - A novel approach is presented to create self-assembling hydrogels. Microspheres
      based on cross-linked dextran were chemically modified with L- or D-oligolactate
      chains. Successful grafting of the particles was confirmed by Fourier transform
      infrared (FT-IR) and Raman and X-ray photoelectron spectroscopy (XPS).
      Rheological analysis of aqueous dispersions of oligolactate-grafted microspheres
      demonstrated that hydrophobic interactions between oligolactate chains on the
      surface of various microspheres resulted in the formation of an almost fully
      elastic gel. A mixture of microspheres substituted with L- or D-oligolactates of
      opposite chirality resulted in gels with highest strength, likely due to
      stereocomplexation between the enantiomers. The network properties could be
      modulated by varying the solid content of the gel, the DS (i.e., number of
      lactate grafts per 100 glucopyranose units) and the DP (i.e., degree of
      polymerization) of the oligolactate grafts. Protein loading of the hydrogels
      could be achieved by simply mixing the microspheres with protein solution.
      Release experiments showed a continuous release of the entrapped lysozyme, with
      50% released after 5 days and full preservation of its enzymatic activity. The
      biocompatible nature of the material, the protein-friendly self-assembly of the
      hydrogel and the possibility to tailor the gel properties, makes this hydrogel
      system an attractive candidate for pharmaceutical and biomedical applications.

PMID- 18081254
TI  - Morphinane alkaloid dimers from Sinomenium acutum.
AB  - Two new morphinane alkaloid dimers, 2,2'-disinomenine (1) and 7',8'-dihydro-1,1'
      disinomenine (2), and known 1, 1'-disinomenine (3), were isolated from ethanol
      extracts of stems of Sinomenium acutum. Their structures were elucidated on the
      basis of spectroscopic methods. The absolute configuration of alkaloids 1-3 was
      determined by direct comparison of their CD spectra with the known alkaloid
      sinomenine. The isolated alkaloids were tested for cytotoxicity against A549,
      P388, and HeLa cell lines, and 1 and 3 showed weak inhibition against A549 and
      Hela cells.

PMID- 18081255
TI  - Angucyclinones from an Indonesian Streptomyces sp.
AB  - Six new angucyclinone polyketides named panglimycins A-F were isolated together
      with the three known metabolites (+)-fujianmycin A, (+)-ochromycinone, and emycin
      C from the bioassay-guided fractionation of the extract of the Indonesian
      Streptomyces strain ICBB8230. The new compounds are highly oxygenated
      angucyclinones that appear to be biosynthetically derived from ochromycinone or
      fujianmycin. Their structures were determined by X-ray crystal analysis,
      interpretation of 1D- and 2D-NMR spectra, and comparison of the data with those
      of structurally related known natural products. Despite structural similarities
      to angucyclinones with antibiotic activities, the panglimycins did not exhibit
      any growth inhibition when tested against several bacteria and fungi.

PMID- 18081256
TI  - Triterpene glycosides from the roots of Astragalus flavescens.
AB  - Six new triterpene saponins, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D
      xylopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-21-epi-kudzusapogenol A (1), 3-O
      alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D
      glucuronopyranosyl-21-epi-kudzusapogenol A (2), 3-O-alpha-L-rhamnopyranosyl-(1-
      >2)-beta-D-xylopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-22-O-beta-D
      glucopyranosyl-21-epi-kudzusapogenol A (3), 3-O-alpha-L-rhamnopyranosyl-(1-->2)
      beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-22-O-beta-D
      glucopyranosyl-21-epi-kudzusapogenol A (4), 3-O-alpha-L-rhamnopyranosyl-(1-->2)
      beta-D-xylopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-22-O-alpha-L
      arabinopyranosyl-21-epi-kudzusapogenol A (5), and 3-O-alpha-L-rhamnopyranosyl-(1-
      >2)-beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-22-O-alpha-L
      arabinopyranosyl-21-epi-kudzusapogenol A (6), were isolated from the roots of
      Astragalus flavescens, together with the known trajanoside B, azukisaponin V, and
      astragalosides IV, VII, and VIII. Their structures were established mainly by 2D
      NMR techniques and mass spectrometry.

PMID- 18081257
TI  - Synthesis and biological evaluation of 10,11-dihydrodictyostatin, a potent
      analogue of the marine anticancer agent dictyostatin.
AB  - By employing a diverted total synthesis strategy with late-stage intermediates,
      10,11-dihydrodictyostatin ( 5) was prepared and evaluated in vitro for growth
      inhibition against a range of human cancer cell lines, including the NCI/ADR
      Taxol-resistant cell line. This novel dictyostatin analogue was found to retain
      potent antimitotic activity, with a comparable profile to discodermolide and
      Taxol, functioning by microtubule stabilization and G2/M arrest. These SAR
      studies provide further insight into the interaction between dictyostatin ( 1)
      and its tubulin target.

PMID- 18081258
TI  - Anti-HIV cyclotides from the Chinese medicinal herb Viola yedoensis.
AB  - Cyclotides are macrocyclic plant peptides characterized by a knotted arrangement
      of three disulfide bonds. They display a range of interesting bioactivities,
      including anti-HIV and insecticidal activities. More than 100 different
      cyclotides have been isolated from two phylogenetically distant plant families,
      the Rubiaceae and Violaceae. In this study we have characterized the cyclotides
      from Viola yedoensis, an important Chinese herb from the Violaceae family that
      has been reported to contain potential anti-HIV agents. From V. yedoensis five
      new and three known cyclotides were identified and shown to have anti-HIV
      activity. The most active of these is cycloviolacin Y5, which is one of the most
      potent of all cyclotides tested so far using in vitro XTT-based anti-HIV assays.
      Cycloviolacin Y5 is the most hydrophobic of the cyclotides from V. yedoensis. We
      show that there is a positive correlation between the hydrophobicity and the anti
      HIV activity of the new cyclotides and that this trend tracks with their ability
      to disrupt membranes, as judged from hemolytic assays on human erythrocytes.

PMID- 18081259
TI  - Proton-conducting glass electrolyte.
AB  - A new porous glass electrolyte consisting of heteropolyacids, i.e.,
      phosphotungstic acid (PWA) and phosphomolybdic acid, was investigated and was
      found to yield a remarkably high proton conductivity of 1.014 S cm(-1) at 30
      degrees C and 85% relative humidity. This is the first time such a high proton
      conductivity value has been reported for a heteropolyacid glass membrane. The
      glass was applied as the electrolyte for an H(2)/O(2) fuel cell, and a maximum
      power density of 41.5 mW/cm(2) at 32 degrees C was attained using this new PWA
      containing electrode.

PMID- 18081260
TI  - Method for microfluidic whole-chip temperature measurement using thin-film
      poly(dimethylsiloxane)/rhodamine B.
AB  - A novel method is presented for on-chip temperature measurements using a
      poly(dimethylsiloxane) (PDMS) thin film dissolved with Rhodamine B dye. This thin
      film is sandwiched between two glass substrates (one of which is 150 microm
      thick) and bonded to a microchannel molded in a PDMS substrate. Whole-chip
      (liquid and substrate) temperature measurements can be obtained via fluorescent
      intensity visualization. For verification purposes, the thin film was tested with
      a tapered microchannel subjected to Joule heating, with resulting axial
      temperature gradients comparing well with numerical simulations. Errors induced
      by the definite film thickness are discussed and accounted for during
      experimental and analytical analysis. Alternative validation using the
      traditional in-channel Rhodamine B injection method was also attempted. The thin
      film has several advantages over traditional methods. First, false intensity
      readings due to adsorption and absorption of Rhodamine B into PDMS channels are
      eliminated. Second, whole-chip temperature measurements are possible. Third,
      separation of working liquid from Rhodamine B dye prevents possible
      electrophoresis effects.

PMID- 18081261
TI  - Poly(ethylene glycol)-functionalized devices for electric field gradient
      focusing.
AB  - Electric field gradient focusing (EFGF) is an equilibrium gradient focusing
      technique that depends on an electric field gradient and a hydrodynamic
      counterflow to focus, concentrate, and separate charged analytes. In this work,
      EFGF devices were fabricated from poly(ethylene glycol) (PEG)-functionalized
      acrylic plastic. The separation channel was formed in an ionically conductive and
      protein-resistant PEG-functionalized hydrogel, which was cast in a changing cross
      sectional cavity in the plastic device. A linear electric field gradient was
      obtained by applying a voltage lengthwise across the shaped hydrogel. Standard
      proteins were used as analytes to demonstrate the performance of these EFGF
      devices. With an increase in counterflow rate or decrease in applied voltage,
      analyte bands broadened, but resolution increased in agreement with theory. To
      reduce analyte band dispersion and improve focusing performance, a protein
      compatible PEG-functionalized monolith was incorporated in the EFGF channel.
      Compared with focusing in an open channel, protein bands in the monolith-filled
      EFGF channel were significantly narrower.

PMID- 18081262
TI  - Charger: combination of signal processing and statistical learning algorithms for
      precursor charge-state determination from electron-transfer dissociation spectra.
AB  - Tandem mass spectrometry in combination with liquid chromatography has emerged as
      a powerful tool for characterization of complex protein mixtures in a high
      throughput manner. One of the bioinformatics challenges posed by the mass
      spectral data analysis is the determination of precursor charge when unit mass
      resolution is used for detecting fragment ions. The charge-state information is
      used to filter database sequences before they are correlated to experimental
      data. In the absence of the accurate charge state, several charge states are
      assumed. This dramatically increases database search times. To address this
      problem, we have developed an approach for charge-state determination of peptides
      from their tandem mass spectra obtained in fragmentations via electron-transfer
      dissociation (ETD) reactions. Protein analysis by ETD is thought to enhance the
      range of amino acid sequences that can be analyzed by mass spectrometry-based
      proteomics. One example is the improved capability to characterize phosphorylated
      peptides. Our approach to charge-state determination uses a combination of signal
      processing and statistical machine learning. The signal processing employs
      correlation and convolution analyses to determine precursor masses and charge
      states of peptides. We discuss applicability of these methods to spectra of
      different charge states. We note that in our applications correlation analysis
      outperforms the convolution in determining peptide charge states. The correlation
      analysis is best suited for spectra with prevalence of complementary ions. It is
      highly specific but is dependent on quality of spectra. The linear discriminant
      analysis (LDA) approach uses a number of other spectral features to predict
      charge states. We train LDA classifier on a set of manually curated spectral data
      from a mixture of proteins of known identity. There are over 5000 spectra in the
      training set. A number of features, pertinent to spectra of peptides obtained via
      ETD reactions, have been used in the training. The loading coefficients of LDA
      indicate the relative importance of different features for charge-state
      determination. We have applied our model to a test data set generated from a
      mixture of 49 proteins. We search the spectra with and without use of the charge
      state determination. The charge-state determination helps to significantly save
      the database search times. We discuss the cost associated with the possible
      misclassification of charge states.

PMID- 18081263
TI  - Correlation of global electrophilicity with the activation energy in single-step
      concerted reactions.
AB  - The experimental energy of activation (Ea) of the single-step concerted oxidation
      process of aliphatic primary alcohols by quinolinium bromochromate (QBC) are
      correlated with the theoretically evaluated global electrophilicity values (w)
      [as proposed by Parr et al. (J. Am. Chem. Soc. 1999, 121, 1922)]. Conceptual
      justification in favor of correlating w of the substrate with Ea involved in a
      single-step concerted reaction is also discussed. The evaluated w values at HF/cc
      pVTZ and MP2/6-31G(d,p) methods are found to be as expected (when we consider
      structural aspects), although there are some inconsistencies in other methods
      [e.g., HF/6-31G(d,p), B3LYP/cc-pVTZ, BLYP/dnp, PW91/dnp, PWC/dnp, VWN/dnp]. The
      reasons for the inconsistencies, even with a superior B3LYP/cc-pVTZ method, are
      discussed thoroughly. It is observed that the higher the value of w, the more the
      value of Ea involved in the process of oxidation of primary alcohols by QBC. The
      present study also reveals that the apparent success of insignificant (i.e., much
      smaller) local electrophilicity values (S+O(OH)), evaluated using Hirshfeld
      population analysis (HPA), in explaining observed trend of experimental Ea values
      turns out to be ambiguous when more significant (i.e., much larger) local
      nucleophilicity values (S-O(OH)) are also compared. This is evident from the
      corresponding correlation coefficient values.

PMID- 18081264
TI  - Ultraviolet cavity ringdown spectra and the S1(n,pi) ring-inversion potential
      energy function for 2-cyclohexen-1-one-d0 and Its 2,6,6-d3 isotopomer.
AB  - The cavity ringdown spectra of 2-cyclohexen-1-one (2CHO) and its 2,6,6-d3
      isotopomer (2CHO-d3) have been recorded in the spectral region near their
      S1(n,pi)<--S0 band origins which are at 26,081.3 and 26,075.3 cm-1, respectively.
      The data allow several of the quantum states of nu39, the ring inversion, to be
      determined for both the ground and excited electronic states. These were utilized
      to calculate the one-dimensional potential energy functions which best fit the
      data. The barriers to inversion for the S0 and S1(n,pi) states were found to be
      1,900 +/- 300 and 3,550 +/- 500 cm-1, respectively. Density functional theory
      calculations predict values of 2,090 and 2,265 cm-1, respectively.

PMID- 18081265
TI  - Magnetic isotope effect on kinetic parameters and quantum beats of radical pairs
      in micellar solution studied by optically detected esr using pulsed microwave.
AB  - We investigated the quantum beats, the oscillation between singlet and triplet
      states of radical pairs induced by the microwave field resonant to one of the
      component radicals. They were observed as the alternation of the yields of the
      component radicals by a nanosecond time-resolved optical absorption with the X
      band (9.15 GHz) resonant microwave pulse. This technique was applied to the
      photochemical reaction of benzophenone, benzophenone-d(10), and benzophenone
      carbonyl-(13)C in a sodium dodecylsulfate micellar solution with a step-by-step
      increase of the resonant microwave pulse width. The yields of the component
      radicals showed alternation with an increase of the microwave pulse width. This
      indicates that the radical pair retains spin coherence in the micellar solution.
      The magnetic isotope effect on the amplitude of the quantum beat was observed.
      The MW effect on the quantum beat of BP-(13)C decreases from 80% to 60% of that
      of BP by irradiation of the pi-pulse MW due to spin-locking. The kinetic
      parameters were also determined using the X- or Ku-band (17.44 GHz) region. They
      are almost similar to each other except for the intersystem recombination rate in
      the system of BP-(13)C, which may be slightly higher than those in other systems.

PMID- 18081266
TI  - Double-hybrid functionals for thermochemical kinetics.
AB  - We propose two new double-hybrid functionals, denoted B2K-PLYP and mPW2K-PLYP,
      which yield thermochemical performance comparable to existing double-hybrid
      functionals but offer superior performance for barrier heights of various kinds.
      We show that the new functionals yield excellent performance for all of the
      following: (a) main-group thermochemistry; (b) main-group thermochemical
      kinetics; (c) late transition metal reactions. In addition, B2K-PLYP performs
      well for weak interactions.

PMID- 18081268
TI  - Balancing the influence of molecular complexity on fingerprint similarity
      searching.
AB  - Differences in molecular complexity and size are known to bias the evaluation of
      fingerprint similarity. For example, complex molecules tend to produce
      fingerprints with higher bit density than simple ones, which often leads to
      artificially high similarity values in search calculations. We introduce here a
      variant of the Tversky coefficient that makes it possible to modulate or
      eliminate molecular complexity effects when evaluating fingerprint similarity.
      This has enabled us to study in detail the role of molecular complexity in
      similarity searching and the relationship between reference and active database
      compounds. Balancing complexity effects leads to constant distributions of
      similarity values for reference and database molecules, independent of how
      compound contributions are weighted. When searching for active compounds with
      varying complexity, hit rates can be optimized by modulating complexity effects,
      rather than eliminating them, and adjusting relative compound weights. For
      reference molecules and active database compounds having different complexity,
      preferred parameter settings are identified.

PMID- 18081269
TI  - Syntheses, crystal structures, and spectral properties of a series of 3,8
      Bisphenyl-1,10-phenanthroline derivatives: precursors of 3,8-Bis(4
      mercaptophenyl)-1,10-phenanthroline and Its ruthenium(II) complex for preparing
      nanocomposite junctions with gold nanoparticles between 1 microm gap gold
      electrodes.
AB  - A multistep synthesis was achieved to obtain 3,8-bis(4-mercaptophenyl)-1,10
      phenanthroline, which has two free thiol end groups with a molecular length of
      1.89 nm, and its ruthenium(II) complex. Five single-crystal structures and UV-vis
      spectra of related intermediates in methanol and the solid state were studied in
      order to obtain additional information on the molecules as well as on the
      supramolecular interactions in the structures. Thermal and electrochemical
      properties of related Ru(II) complexes were also involved. 3,8-Bis(4
      mercaptophenyl)-1,10-phenanthroline and one of its ruthenium(II) complexes were
      then treated with gold nanoparticles (Au-NPs) via in situ thiol-to-thiol ligand
      exchange in the presence of two facing Au electrodes with a 1 x 1 microm(2) gap.
      Stable molecular junctions composed of self-assembled films were produced as
      revealed by an obvious increase of the conductivity between the Au electrodes,
      wherein dithiols-bridged Au-NPs were attached to the electrodes by means of Au-S
      bonded contacts. Temperature-dependent current-voltage (I-V) measurements for the
      junctions were performed in the temperature range of 7-300 K, and classical
      Arrhenius plots and their linear fits were obtained to determine the average
      activation energies (DeltaE) of these devices. It is found that when the Ru(II)
      ion is introduced, the conductivity of the nanodevice is increased and the energy
      barrier is lowered under the same experimental conditions.

PMID- 18081270
TI  - Supramolecular isomerism with polythreaded topology based on [Mo8O26]4- isomers.
AB  - Two compounds, namely, [Cu(bbi)](2)[Cu(2)(bbi)(2)(delta-Mo(8)O(26))0.5][alpha
      Mo(8)O(26)]0.5 (1) and [Cu(bbi)][Cu(bbi)(theta-Mo(8)O(26))0.5] (2), where bbi is
      1,1'-(1,4-butanediyl)bis(imidazole), were synthesized under hydrothermal
      conditions at different pH values. Their crystal structures were determined by X
      ray diffraction. Compounds 1 and 2 are supramolecular isomers with a polythreaded
      topology based on octamolybdate building blocks.

PMID- 18081271
TI  - Photochemical synthesis and reactivity studies of dirhenacarboranes.
AB  - Ultraviolet irradiation of [PPh(4)][closo-1-CB(8)H(9)] with [Re(2)(CO)(10)] in
      THF (tetrahydrofuran) at ambient temperature affords the dirhenacarborane anion
      [6,10-{Re(CO)(4)}-10-(micro-H)-6,6,6-(CO)(3)-closo-6,1-ReCB(8)H(8)]-, isolated as
      its [PPh(4)]+ salt (1). Further irradiation of 1 yields a second isomeric anion
      [6,10-{Re(CO)(4)}-6-(micro-H)-10,10,10-(CO)(3)-closo-10,1-ReCB(8)H(8)]- that was
      characterized as a [N(PPh(3))(2)]+ salt (2). Reaction of 1 with NOBF(4) produces
      the neutral dirhenacarborane compound [8,10-{Re(CO)(4)}-8,10-(micro-H)2-6,6
      (CO)(2)-6-NO-closo-6,1-ReCB(8)H(7)] (3). Compounds 1-3 all consist of a central
      {closo-ReCB(8)} cluster with a second rhenium center which is exo-polyhedral.
      Attempts to substitute the carbonyl ligands of 3 with other donor ligands such as
      phosphines, isocyanides, or alkynes resulted in loss of the exo-polyhedral
      rhenium moiety and formation of a monorhenium anion, [6,6-(CO)(2)-6-NO-closo-6,1
      ReCB(8)H(9)]-, isolated as its [N(PPh(3))(2)]+ salt (4). The heterometallic
      dimetallacarborane species, [6,7,10-{Cu(PPh(3))}-7,10-(micro-H)2-6,6-(CO)(2)-6-NO
      closo-6,1-ReCB(8)H(7)] (5) and [6,7-{Au(PPh(3))}-7-(micro-H)-6,6-(CO)(2)-6-NO
      closo-6,1-ReCB(8)H(8)] (6) were formed from reactions of 4 with {Cu(PPh(3))}+ and
      {Au(PPh(3))}+, respectively. Similarly, reaction of 4 with {Ir(CO)(PPh(3))(2)}+
      afforded two products, [6,10-{Ir(micro-PPh(2))(Ph)(CO)(PPh(3))}-10-(micro-H)-6-CO
      6-NO-closo-6,1-ReCB(8)H(8)] (7) and [6,9,10-{Ir(micro-PPh(2))(H)(PPh(3))}-9
      (micro-H)-6-CO-6-NO-10-Ph-closo-6,1-ReCB(8)H(8)] (8). The solid-state structures
      of compounds 1-8 were all unequivocally established by single-crystal X-ray
      diffraction experiments.

PMID- 18081272
TI  - Influence of the electronics of the phosphine ligands on the H-H bond elongation
      in dihydrogen complexes.
AB  - Five new monocationic dihydrogen complexes of ruthenium of the type trans
      [RuCl(eta(2)-H(2))(PP)(2)][BF(4)] (PP = bis-1,2(diarylphosphino)ethane, aryl = p
      fluorobenzyl, 1a, benzyl, 2a, m-methylbenzyl, 3a, p-methylbenzyl, 4a, p
      isopropylbenzyl, 5a) have been prepared by protonating the precursor hydride
      complexes trans-[RuCl(H)(PP)(2)] using HBF(4).OEt(2). The dihydrogen complexes
      are quite stable and have been isolated in the solid state. The intact nature of
      the H-H bond in these derivatives has been established from the short spin
      lattice relaxation times (T1, ms) and observation of substantial H, D couplings
      in the HD isotopomers. The H-H bond distances (dHH, A) increase systematically
      from 0.97 to 1.03 A as the electron-donor ability of the substituent on the
      diphosphine ligand increases from the p-fluorobenzyl to the p-isopropylbenzyl
      moiety. The d(HH) in trans-[Ru(eta(2)
      H(2))(Cl)((C(6)H(5)CH(2))(2)PCH(2)CH(2)P(CH(2)C(6)H(5))(2))(2)][BF(4)], 2a, was
      found to be 1.08(5) A by X-ray crystallography. In addition, two new 16-electron
      dicationic dihydrogen complexes of the type [Ru(eta(2)-H(2))(PP)(2)][OTf](2) (PP
      = (ArCH(2))(2)PCH(2)CH(2)P(CH(2)Ar)(2), Ar = m-CH(3)C(6)H(4-), 6a, p
      CH(3)C(6)H(4)-, 7a) have also been prepared and characterized. These derivatives
      were found to possess elongated dihydrogen ligands.

PMID- 18081273
TI  - Lead and aluminum bonding in Pb-AI metaphosphate glasses.
AB  - The bonding properties of cations in phosphate glasses determine many short- and
      medium-range structural features in the glass network, hence influencing bulk
      properties. In this work, Pb-Al-metaphosphate glasses (1 -
      x)Pb(PO(3))(2).xAI(PO(3))(3) with 0 < or = x < or = 1 were analyzed to determine
      the effect of the substitution of Pb by AI on the glass structure in the
      metaphosphate composition. The glass transition temperature and density were
      measured as a function of the Al concentration. The vibrational and structural
      properties were probed by Raman spectroscopy and nuclear magnetic resonance of
      (31)P, (27)AI, and (207)Pb. Aluminum incorporates homogeneously in the glass
      creating a stiffer and less packed network. The average coordination number for
      AI decreases from 5.9 to 5.0 as x increases from 0.1 to 1, indicating more
      covalent AI-O bonds. The coordination number of Pb in these glasses is greater
      than 8, showing an increasing ionic behavior for compositions richer in AI. A
      quantitative analysis of the phosphate speciation shows definite trends in the
      bonding of AIO(n) groups and phosphate tetrahedra. In glasses with x < 0.48,
      phosphate groups share preferentially only one nonbridging O corner with an
      AIO(n) coordination polyhedron. For x > 0.48 more than one nonbridging O can be
      linked to AIO(n) polyhedra. There is no corner sharing of O between AIO(n) and
      PbO(n) polyhedra nor between AIO(n) themselves throughout the compositional
      range. The PbO(n) coordination polyhedra show considerable nonbridging O sharing,
      with each O participating in the coordination sphere of at least two Pb. The
      bonding preferences determined for Al are consistent with the behavior observed
      in Na-AI and Ca-AI metaphosphates, indicating this may be a general behavior for
      ternary phosphate glasses.

PMID- 18081274
TI  - Template-assisted synthesis of shape-controlled Rh2P nanocrystals.
AB  - When reacted with trioctylphosphine at approximately 360 degrees C, rhodium
      nanocrystals convert to rhodium phosphide Rh(2)P nanocrystals. Careful control
      over synthetic variables, such as temperature, stabilizing ligands, and
      cosolvents, can result in Rh(2)P nanocrystals with shapes that reflect the Rh
      nanocrystal templates. Accordingly, Rh nanocrystals with multipod, cube- and
      triangle-derived shapes convert to Rh(2)P nanocrystals that maintain the shape of
      their Rh precursors. Both dense and hollow Rh(2)P nanocrystals can be generated
      using a single unified chemical conversion strategy. These empirical guidelines
      for generating a morphologically diverse library of Rh(2)P nanocrystals provide
      important insights into shape conservation using nanocrystal templates and will
      likely be portable to other multielement systems for which rigorous shape
      controlled synthesis remains challenging.

PMID- 18081275
TI  - Nickel(II) complexes containing bidentate amido phosphine ligands derived from
      alpha-iminophosphorus ylides: synthesis and structural characterization.
AB  - The reactions of prop-2-ynyltriphenylphosphonium bromide with a series of primary
      aromatic or aliphatic amines in refluxing acetonitrile generated the
      corresponding 2-hydrocarbylaminoprop-1-enyltriphenylphosphonium bromide
      [RNHC(Me)=CHPPh(3)]+Br- (R = 2,6-C(6)H(3)iPr(2) (1a), 2,6-C(6)H(3)Me(2) (1b), Ph
      (1c), t-Bu (1d)) as crystalline solids. Deprotonation of 1a-d with NaH in THF at 
      35 degrees C afforded the alpha-iminophosphorus ylides RN=C(Me)CH=PPh(3) (2a-d)
      in high yield. Spectroscopic and crystallographic data of 2 suggest a strong
      intramolecular interaction between the imino nitrogen and the phosphorus atom. In
      contrast to N-arylated 2a-c, the N-tert-butyl-derived 2d is extremely moisture
      sensitive. Hydrolysis of 2d led to elimination of benzene and generated
      concomitantly the phosphine oxide 3d that contains an ene-amine functionality.
      The reactions of 2a-c with Ni(COD)(2) in the presence of an excess amount of
      pyridine in toluene produced the divalent nickel complexes of the type [kappa(2)
      RNC(Me)=CHPPh(2)]Ni(Ph)(Py) (4a-c). The solution and solid-state structures of
      these new compounds are presented.

PMID- 18081276
TI  - Coordination chemistry of a model for the GP cofactor in the Hmd hydrogenase:
      hydrogen-bonding and hydrogen-transfer catalysis.
AB  - Cp(*)M(2+) complexes (M = Rh, Ir; Cp(*) = C(5)Me(5)) are described for 6
      (carboxymethyl)-4-methyl-2-hydroxypyridine (cmhpH(2)), an analogue of the
      guanylylpyridone cofactor in the hydrogenase Hmd. Three findings indicate that
      Cp(*)M(Hcmhp)(+) stabilizes the binding of hydrogen-bond acceptors to the sixth
      coordination site: (i) water binds in preference to Cl-, (ii) the adduct
      Cp(*)Rh(cmhp)(2-hydroxypyridine) exhibits a very short intramolecular hydrogen
      bond (r(o-o) = 2.38 A; (1)H NMR delta(H) 17.2), and (iii) Cp(*)Ir(cmhpH)Cl
      efficiently catalyzes the dehydrogenation of PhCH(OH)Me to PhC(O)Me.

PMID- 18081277
TI  - Twofold hydrogallation of C triple bonds c triple bonds by H-GaCl(2)-synthesis of
      chelating Lewis acids and their application in adduct formation.
AB  - The twofold addition of Ga-H to Ctriple bonds C triple bonds (hydrogallation) did
      not succeed by treatment of alkynes with an excess of dialkylgallium hydrides. In
      contrast, double hydrogallation was easily achieved by the reactions of H-GaCl(2)
      with trimethylsilyl-substituted alkynes [trimethylsilylphenylethyne and 1,4
      bis(trimethylsilylethynyl)benzene] in appropriate stoichiometric ratios. The
      monoalkyne yielded the compound [H(5)C(6)-CH(2)-C(SiMe(3))(GaCl(2))(2)](2), 1,
      which was only sparingly soluble in n-hexane. Crystal structure determination
      revealed a dimeric formula unit possessing two parallel Ga(2)Cl(2) heterocycles
      in the solid state. Treatment of the dialkyne with four equivalents of the
      hydride gave a colorless precipitate, which was completely insoluble in
      hydrocarbons. Addition of diethyl ether to both products afforded soluble and
      monomeric etherates 1(OEt(2))(2) and 2 in which the two or four gallium atoms,
      respectively, were coordinated by ether molecules. Preliminary experiments with
      simple Lewis bases showed the principle capability of 1 to act as an effective
      chelating Lewis acid. Adducts of the type [H(5)C(6)-CH(2)
      C(SiMe(3))(GaCl(2))(GaClX)(micro-Cl)]- (4-6) resulted upon treatment with halide
      ions (X = Cl, Br, I).

PMID- 18081278
TI  - Addition of alkyl radicals to transition-metal-coordinated CO: calculation of the
      reaction of [Ru(CO)5] and related complexes and relevance to alkane
      carbonylation.
AB  - Electronic structure methods have been used to study the transition state and
      products of the reaction between alkyl radicals and CO coordinated in transition
      metal complexes. At the B3LYP DFT level, methyl addition to a carbonyl of
      [Ru(CO)5] or [Ru(CO)3(dmpe)] is calculated to be about 6 kcal/mol more exothermic
      than addition to free CO. In contrast, methyl addition to [Mo(CO)6] is 12
      kcal/mol less exothermic than addition to CO, while the reaction enthalpy of
      methyl addition to [Pd(CO)4] is comparable to that of free CO. Related results
      are obtained at the CCSD-T level and for the reactions of the cyclohexyl radical.
      The transition state for these reactions is characterized by significant
      distortion of the geometry of the reactant complex, which include lengthening and
      bending of the M-CO bond, but with negligible C-C bond formation. Accordingly,
      the activation energy for addition to coordinated carbonyls is 2-10 kcal/mol
      greater than that of addition to free CO. Additional calculations were also
      carried out on representative unsaturated metal carbonyls. The calculated results
      afford an understanding of the mechanism of previously reported photochemical
      alkane carbonylation systems utilizing d(8)-ML5 metal carbonyls as cocatalysts.
      In particular, it is strongly indicated that such systems operate via direct
      attack by an alkyl radical at a CO ligand, a reaction that has not previously
      been proposed.

PMID- 18081279
TI  - Oxidative diamination of alkenes with ureas as nitrogen sources: mechanistic
      pathways in the presence of a high oxidation state palladium catalyst.
AB  - A first palladium-catalyzed intramolecular diamination of unfunctionalized
      terminal alkenes has recently been reported. This study investigates the details
      of its mechanistic course based on NMR titration, kinetic measurements
      competition experiments, and deuterium labeling. It concludes a two-step
      procedure consisting of syn-aminopalladation with an unligated palladium(II)
      catalyst state followed by oxidation to palladium(IV) and subsequent C-N bond
      formation to give the final products as cyclic diamines. Related reactions
      employing sulfamides give rise to aminoalkoxy-functionalization of alkenes. This
      process was investigated employing deuterated alkenes and found to follow an
      identical mechanism where stereochemistry is concerned. It exemplifies the
      importance of cationic palladium(IV) intermediates prior to the final reductive
      elimination from palladium and proves that the nucelophile for this step stems
      from the immediate coordination sphere of the palladium(IV) precursor. These
      results have important implications for the general development of alkene 1,2
      difunctionalization and for the individual processes of aminopalladation and
      palladium-catalyzed C(alkyl)-N bond formation.

PMID- 18081280
TI  - Dithiabenzisapphyrin: a core-modified sapphyrin bearing exocyclic double bonds at
      the meso-positions.

PMID- 18081281
TI  - Insight into the mechanisms of cooperative self-assembly: the "sergeants-and
      soldiers" principle of chiral and achiral C3-symmetrical discotic triamides.
AB  - On the basis of temperature-dependent UV-vis and circular dichroism (CD)
      spectroscopy measurements, we observed that C3-symmetrical discotic molecules,
      chiral (R)-1 and achiral 2, both self-assemble in a highly cooperative fashion.
      Chiral (R)-1 shows a higher degree of cooperativity, meaning it requires a larger
      nucleus before elongation sets in, as compared to achiral 2. Next to that, we
      investigated the mechanism of the "sergeants-and-soldiers" principle, where we
      found that the chiral sergeant (R)-1 strongly amplifies the preference in
      handedness of the mixed stacks of (R)-1 and 2. However, the elongation
      temperature and the degree of cooperativity are linearly dependent on both, at
      least in the regime above 4% of sergeant in the mixed system. Remarkably, we
      observed that at room temperature a fast exchange on the second time scale exists
      between molecules and stacks of sergeant (R)-1 and soldier 2, and that
      interconversion between M and P helices is fast at this temperature.

PMID- 18081282
TI  - Electrochemistry and electrogenerated chemiluminescence of 3,6
      di(spirobifluorene)-N-phenylcarbazole.
AB  - We report here the electrochemistry, luminescence, and electrogenerated
      chemiluminescence (ECL) of 3,6-dispirobifluorene-N-phenylcarbazole (DSBFNPC).
      DSBFNPC contains two spirobifluorene groups covalently attached to the N
      phenylcarbazole core. The optimized geometry as determined from semiempirical
      MNDO calculations shows that the phenyl group is twisted 89 degrees from the
      plane of central carbazole, indicating a lack of electron delocalization between
      these groups. However, the two fluorene rings of each spirobifluorene group are
      twisted 58 degrees relative to each other and two spirobifluorene groups are
      twisted 64 degrees from the N-phenylcarbazole ring, suggesting some charge
      delocalization among these groups. The cyclic voltammetry of this compound shows
      two reversible oxidation waves (assigned to the formation of the cation and
      dication) and a two-electron reduction wave that becomes reversible at higher
      scan rates (assigned to formation of anion). Digital simulations were carried out
      to obtain details of the electrochemical processes, and electrochemical behavior
      was compared to that of phenylcarbazole (PC). Upon cycling between the oxidation
      and reduction waves, ECL is produced by radical ion annihilation. The
      photophysical properties of DSBFNPC show a strong resemblance to the parent
      compound, PC, and the ECL spectrum produced via radical ion annihilation shows
      good agreement with the fluorescence emission spectrum of DSBFNPC.

PMID- 18081283
TI  - Verification of biochemical activity for proteins nanografted on gold surfaces.
AB  - We demonstrate that the Atomic Force Microscope (AFM) can be used to immobilize a
      dicysteine-terminated protein (Maltose Binding Protein, MBP-cys-cys for short) at
      well-defined locations directly on gold substrates via nanografting and
      characterize the in situ bioactivity of these proteins within the fabricated
      nanopatterns. This method exploits the high spatial and orientational control of
      the protein monolayer assembly allowed by nanografting, combined with the high
      sensitivity of the AFM for detecting ligand-binding events. The maltose-mediated
      conformational changes within the MBP have been found to change the AFM-tip
      protein interaction, therefore causing the frictional signal to change. Our
      measurements show that the protein ligand-binding function is maintained upon the
      immobilization process and is not affected by (a) the addition of the cysteine
      dipeptide, (b) the spatial confinement associated with nanografting, and (c) the
      interaction between the protein and the Au substrate. These surface-confined
      proteins can also be regenerated, and their frictional response is reproducible
      through several maltose exposure/washing cycles. By measuring the change in the
      frictional force above the protein nanopatterns as a function of maltose
      concentration, we determined the dissociation constant for the MBP-cys
      cys/maltose system to be kd = (1 +/- 0.04) microM. Our results show that the MBP
      cys-cys system provides a very sensitive surface-based, protein nanobiosensor for
      maltose detection at the attogram level (approximately 100 nM concentration). The
      implications of our study for the fabrication of molecular-scale biological
      sensors are discussed at the end of the paper.

PMID- 18081284
TI  - Synthesis and redox behavior of flavin mononucleotide-functionalized single
      walled carbon nanotubes.
AB  - In this contribution, we describe the synthesis and covalent attachment of an
      analogue of the flavin mononucleotide (FMN) cofactor onto carboxylic
      functionalities of single-walled carbon nanotubes (SWNTs). The synthesis of FMN
      derivative (12) was possible by coupling flavin H-phosphonate (9) with an
      aliphatic alcohol, using a previously unreported N-(3-dimethylaminopropyl)-N'
      ethylcarbodiimide hydrochloride coupling. We found that the flavin moiety of 12
      SWNT shows a strong pi-pi interaction with the nanotube side-walls. This leads to
      a collapsed FMN configuration that quenches flavin photoluminescence (PL). The
      treatment of 12-SWNT with sodium dodecyl sulfate (SDS) overcomes this strong
      nanotube/isoalloxazine interaction and restores the FMN into extended
      conformation that recovers its luminescence. In addition, redox cycling as well
      as extended sonication were proven capable to temporally restore PL as well.
      Cyclic voltammetry of FMN onto SWNT forests indicated profound differences for
      the extended and collapsed FMN configurations in relation to oxygenated nanotube
      functionalities that act as mediators. These findings provide a fundamental
      understanding for flavin-related SWNT nanostructures that could ultimately find a
      number of usages in nanotube-mediated biosensing devices.

PMID- 18081285
TI  - Isomagnetophoresis to discriminate subtle difference in magnetic susceptibility.

PMID- 18081286
TI  - DNA-protein cross-links between guanine and lysine depend on the mechanism of
      oxidation for formation of C5 vs C8 guanosine adducts.
AB  - The reaction between N(alpha)-acetyllysine methyl ester (Lys) and 2'
      deoxyguanosine (dGuo) was used to study structural aspects of DNA-protein cross
      link (DPC) formation. The precise structure of DPCs depended on the nature of the
      oxidant and cross-linking reactions in which a series of different oxidation
      conditions generated a distribution of adducts, principally
      spirodiiminodihydantoins with lysine appended at the purine position of C5 (5-Lys
      Sp), C8 (8-Lys-Sp), or both C5 and C8 (5,8-diLys-Sp). Singlet oxygen oxidation of
      dGuo produced 5-Lys-Sp exclusively when Rose Bengal or methylene blue was used to
      photochemically generate (1)O2 in the presence of Lys, whereas riboflavin or
      benzophenone-mediated photochemistry generated lysine radicals and led to C8
      adduct formation, yielding 8-Lys-Sp and 5,8-diLys-Sp. Notably, the yield of dGuo
      modifications from riboflavin photooxidation increased dramatically in the
      presence of lysine. Oxidation of deoxyguanosine/lysine mixtures with Na2IrCl6 or
      sulfate radicals produced both 5-Lys-Sp and 8-Lys-Sp. The same adducts were
      formed in single and double-stranded oligodeoxynucleotides, and these could be
      analyzed after nuclease digestion. Adduct formation in duplex DNA was somewhat
      dependent on the accessibility of lysine to C5 vs C8 of the purine. No adduct
      formation was detected between lysine and the other nucleobases T, C, or A.
      Overall, the precise location of adduct formation at C5 vs C8 of guanine appears
      to be diagnostic of the oxidation pathway.

PMID- 18081287
TI  - Strictosidine synthase: mechanism of a Pictet-Spengler catalyzing enzyme.
AB  - The Pictet-Spengler reaction, which yields either a beta-carboline or a
      tetrahydroquinoline product from an aromatic amine and an aldehyde, is widely
      utilized in plant alkaloid biosynthesis. Here we deconvolute the role that the
      biosynthetic enzyme strictosidine synthase plays in catalyzing the
      stereoselective synthesis of a beta-carboline product. Notably, the rate
      controlling step of the enzyme mechanism, as identified by the appearance of a
      primary kinetic isotope effect (KIE), is the rearomatization of a positively
      charged intermediate. The KIE of a nonenzymatic Pictet-Spengler reaction
      indicates that rearomatization is also rate-controlling in solution, suggesting
      that the enzyme does not significantly change the mechanism of the reaction.
      Additionally, the pH dependence of the solution and enzymatic reactions provides
      evidence for a sequence of acid-base catalysis steps that catalyze the Pictet
      Spengler reaction. An additional acid-catalyzed step, most likely protonation of
      a carbinolamine intermediate, is also significantly rate controlling. We propose
      that this step is efficiently catalyzed by the enzyme. Structural analysis of a
      bisubstrate inhibitor bound to the enzyme suggests that the active site is
      exquisitely tuned to correctly orient the iminium intermediate for productive
      cyclization to form the diastereoselective product. Furthermore, ab initio
      calculations suggest the structures of possible productive transition states
      involved in the mechanism. Importantly, these calculations suggest that a
      spiroindolenine intermediate, often invoked in the Pictet-Spengler mechanism,
      does not occur. A detailed mechanism for enzymatic catalysis of the beta
      carboline product is proposed from these data.

PMID- 18081288
TI  - Chloride anion controlled molecular "switching". Binding of 2,5,7-trinitro-9
      dicyanomethylenefluorene-C60 by tetrathiafulvalene calix[4]pyrrole and
      photophysical generation of two different charge-separated states.

PMID- 18081289
TI  - Programming multiple protein patterns on a single DNA nanostructure.

PMID- 18081290
TI  - Competitive aryl-iodide vs aryl-aryl reductive elimination reactions in Pt(IV)
      complexes: experimental and theoretical studies.
AB  - The platinum(IV) complex trans-(dmpe)Pt(IV)(Ar)2I2 (2, dmpe = 1,2
      dimethylphosphinoethane, Ar = 4-FC6H4) rapidly reacts, upon moderate heating in
      solution under ambient light, via two distinct pathways: isomerization to the
      corresponding cis-isomer (3) and Ar-I reductive elimination to give
      (dmpe)Pt(II)(Ar)I (4). Complex 3 undergoes, upon prolonged heating at high
      temperatures, an exclusive Ar-Ar reductive elimination reaction to give
      (dmpe)Pt(II)I2. Experimental and DFT studies showed that the 2-to-3 isomerization
      proceeds via three pathways: photochemical or thermal phosphine chelate opening
      and a mechanism involving cleavage of the Pt-I bond. The isomerization reaction
      is significantly slowed down but not stopped in the absence of light or in the
      presence of an excess of tetra-n-butylammonium iodide. On the other hand, the Ar
      I reductive elimination from 2 proceeds via the Pt(delta+)-I(delta-) ion pairlike
      transition state. Use of the rigid dmpe analogue 1,2-dimethylphosphinobenzene
      (dmpbz) as the ligand shuts down the chelate ring-opening isomerization pathway
      and enables faster Ar-I reductive elimination thus making the latter reaction the
      major reaction route for the dmpbz supported trans-diiodo Pt(IV) complex 8.

PMID- 18081291
TI  - An enantioselective organocatalytic oxidative dearomatization strategy.

PMID- 18081292
TI  - Alpha-amination of nitrogen heterocycles: ring-fused aminals.

PMID- 18081293
TI  - Intramolecular crosslinking of an optically inactive 3(10)-helical peptide:
      stabilization of structure and helix sense.

PMID- 18081294
TI  - Highly efficient, living coordinative chain-transfer polymerization of propene
      with ZnEt2: practical production of ultrahigh to very low molecular weight
      amorphous atactic polypropenes of extremely narrow polydispersity.

PMID- 18081295
TI  - Simple, efficient, and modular syntheses of polyene natural products via
      iterative cross-coupling.

PMID- 18081296
TI  - Fully intermolecular nickel-catalyzed three-component couplings via internal
      redox.

PMID- 18081297
TI  - Direct coupling of catharanthine and vindoline to provide vinblastine: total
      synthesis of (+)- and ent-(-)-vinblastine.

PMID- 18081298
TI  - Simple and Effective 3D Recognition of Domoic Acid Using a Molecularly Imprinted
      Polymer [J. Am. Chem. Soc. 2007, 129, 13626-13632].

PMID- 18081299
TI  - Synthetic studies on altemicidin: stereocontrolled construction of the core
      framework.
AB  - The stereoselective synthesis of the key intermediate for altemicidin has been
      accomplished. The synthesis commenced with a bicyclo[3.3.0] framework, which was
      readily obtained via an intramolecular C-H insertion reaction. A Curtius
      rearrangement was employed as a key step to stereoselectively construct the beta
      hydroxyl alpha-disubstituted-alpha-amino acid structure. Synthesis of vinylogous
      urea was achieved using hydrolysis of nitrile intermediate.

PMID- 18081300
TI  - A facile synthesis of 2-methylquinolines via Pd-catalyzed aza-wacker oxidative
      cyclization.
AB  - A novel Pd-catalyzed Wacker-type oxidative cyclization under air is described. By
      using this cyclization, a series of 2-methylquinolines are readily prepared with
      good yields under mild conditions.

PMID- 18081301
TI  - Anion recognition by 1,2,3-triazolium receptors: application of click chemistry
      in anion recognition.
AB  - Cyclic and acyclic bile acid-based 1,2,3-triazolium receptors which show
      remarkable ability to recognize anions through C-H...X- hydrogen bond
      interactions have been synthesized using click chemistry.

PMID- 18081302
TI  - Development of a novel Pd-catalyzed N-acyl vinylogous carbamate synthesis for the
      key intermediate of ICE inhibitor VX-765.
AB  - A novel Pd-catalyzed coupling of Cbz-protected proline amide with 4-bromo-5
      ethoxyfuran-2(5H)-one was developed for the synthesis of the P1-P2 unit (5) of VX
      765. The process afforded quantitative coupling in the presence of water,
      providing a 1:1 mixture of 5 and its ethoxy epimer epi-5. Compound 5 was isolated
      as a single diastereomer via fractional crystallization, which was
      stereoselectively converted to 17 via hydrogenation, and subsequently transformed
      to VX-765. Nine examples of the Pd coupling are presented with yields ranging
      from 76-98%.

PMID- 18081303
TI  - Stereoselective RhI-catalyzed tandem conjugate addition of boronic acids-Michael
      cyclization.
AB  - The first examples of the stereoselective sequence RhI-catalyzed tandem conjugate
      addition of boronic acids to enones-Michael cyclization, is reported. The
      reaction is carried out in dioxane-H2O at rt, and 1,2,3-trisubstituted indans are
      obtained in a highly regio- and stereoselective fashion.

PMID- 18081304
TI  - Synthesis of a nanocar with an angled chassis. Toward circling movement.
AB  - Nanocars with an angled chassis have been synthesized and imaged using scanning
      tunneling microscopy. These angled chassis nanocars were designed to further our
      understanding of the directional control and surface-rolling capabilities of this
      class of nanomachines. The alkylated carbazole inner core might enable the
      molecular scaffold to produce circular rolling motions of the nanovehicles on
      surfaces.

PMID- 18081305
TI  - Alternative and expedient asymmetric syntheses of L-(+)-noviose.
AB  - L-(+)-noviose, the sugar component of the antibiotic novobiocin, was synthesized
      from readily available non-carbohydrate starting materials relying on
      stoichiometric and asymmetric processes by two independent methods, comprising
      six and nine steps, in 27 and 20% overall yields, respectively.

PMID- 18081306
TI  - Macromolecular salen catalyst with largely enhanced catalytic activity.
AB  - A dinuclear copper(II) Schiff-base complex was immobilized in a poly(acrylate)
      matrix by emulsion polymerization. The spheric microbeads were used for aerobic
      catalytic oxidation of 3,5-di-tert-butylcatechol into 3,5-di-tert-butylquinone in
      methanol at ambient temperature to study the contribution of the macromolecular
      matrix to the overall rate acceleration of the reaction. The polymeric catalyst
      catalyzes the oxidation about 1 order of magnitude faster (kcat/knon = 470,000)
      than its low molecular weight analogue (kcat/knon = 60,000).

PMID- 18081307
TI  - Engineered systems for detection and discovery of nuclear hormone-like compounds.
AB  - Biomolecular engineering has many applications in the identification of
      potentially therapeutic compounds. An important class of these compounds is those
      that bind and modulate the activity of the human nuclear hormone receptors
      (NHRs). NHRs are typically made up of clearly defined domains with known
      function, including one that mediates ligand recognition and NHR activation.
      Engineered systems that include these ligand-binding domains (LBDs) can be used
      to identify potential therapeutic ligands that target a given NHR. These methods
      must couple the binding event to a readily detectable signal, ideally in a high
      throughput format. Recent efforts have delivered a variety of new techniques,
      including those that involve fusions of LBDs to easily assayed reporter proteins.
      In some cases these systems allow hormone-dependent selectable phenotypes to be
      generated in non-native hosts, providing potential tools for both isolation and
      evolution of new therapeutics in vivo. Here we provide an overview and a
      comparison of many of the available tools in this area, with an emphasis on a
      novel allosteric hormone-regulated sensor protein that provides ligand-dependent
      phenotypes in the relatively simple background of Escherichia coli bacterial
      cells.

PMID- 18081308
TI  - S2 deletion variants of human PRL receptors demonstrate that extracellular domain
      conformation can alter conformation of the intracellular signaling domain.
AB  - Using spacers between the C-termini of the long (LF) or short (SF) human
      prolactin receptors and luciferase/GFP such that bioluminescence resonance energy
      transfer (BRET) occurred minimally in intact versions of these receptors in the
      absence of ligand, we have monitored the BRET signal after deletion of regions of
      the extracellular domain (ECD). Deletion of S2 produced ligand-independent BRET
      for only those pairings normally occurring in the presence of ligand with the
      intact receptor. Deletion of the similarly sized S1, or S1 plus S2, produced no
      ligand-independent or -dependent BRET. When deleted receptors were transfected
      into human breast (T47D) or prostate (DU145) cancer cells incubated in the
      absence of added prolactin (PRL) and presence of anti-PRL, expression of the
      DeltaS2LF resulted in increased cell number, whereas expression of the intact
      receptor did not. When endogenous beta-casein expression was examined in T47D
      cells, the DeltaS2LF and DeltaS2F1a both showed ligand-independent activation of
      transcription, again not duplicated by the intact receptor. Paired with evidence
      in the literature for predimerization of PRLRs, these results demonstrate that
      altered ECD conformation, and not just a change in bulk, produces altered
      conformation of the intracellular signaling region of the receptors, supporting
      the concept that ligand binding to the ECD of intact predimerized receptors could
      initiate signaling. In addition, the current work supports a dual proliferative
      and differentiative role for the LF receptor, but only a differentiative role for
      the SF1a receptor. Naturally occurring DeltaS2 PRL receptors (PRLR) were also
      found in normal and cancerous human cells. This additionally suggests a
      heretofore unappreciated ligand-independent role for PRLRs.

PMID- 18081309
TI  - Basic folded and low-populated locally disordered conformers of SUMO-2
      characterized by NMR spectroscopy at varying pressures.
AB  - SUMO proteins, a group of post-translational ubiquitin-like modifiers, have
      target enzymes (E1 and E2) like other ubiquitin-like modifiers, e.g., ubiquitin
      and NEDD8, but their physiological roles are quite different. In an effort to
      determine the characteristic molecular design of ubiquitin-like modifiers, we
      have investigated the structure of human SUMO-2 in solution not only in its basic
      folded state but also in its higher-energy state by utilizing standard and
      variable-pressure NMR spectroscopy, respectively. We have determined average
      coordinates of the basic folded conformer at ambient pressure, which gives a
      backbone structure almost identical with those of ubiquitin and NEDD8. We have
      further investigated conformational fluctuations in a wide conformational space
      using variable-pressure NMR spectroscopy in the range of 30-3 kbar, by which we
      find a low-populated ( approximately 2.5%) alternative conformer preferentially
      disordered in the enzyme-binding segment. The alternative conformer is
      structurally very close to but markedly different in equilibrium population from
      those for ubiquitin and NEDD8. These results support our notion that post
      translational ubiquitin-like modifiers are evolutionarily designed for function
      both structurally and thermodynamically in their low-populated, high-energy
      conformers rather than in their basic folded conformers.

PMID- 18081310
TI  - A quantitative index of substrate promiscuity.
AB  - Catalytic promiscuity is a widespread, but poorly understood, phenomenon among
      enzymes with particular relevance to the evolution of new functions, drug
      metabolism, and in vitro biocatalyst engineering. However, there is at present no
      way to quantitatively measure or compare this important parameter of enzyme
      function. Here we define a quantitative index of promiscuity (I) that can be
      calculated from the catalytic efficiencies of an enzyme toward a defined set of
      substrates. A weighted promiscuity index (J) that accounts for patterns of
      similarity and dissimilarity among the substrates in the set is also defined.
      Promiscuity indices were calculated for three different enzyme classes: eight
      serine and cysteine proteases, two glutathione S-transferase (GST) isoforms, and
      three cytochrome P450 (CYP) isoforms. The proteases ranged from completely
      specific (granzyme B, J = 0.00) to highly promiscuous (cruzain, J = 0.83). The
      four drug-metabolizing enzymes studied (GST A1-1 and the CYP isoforms) were
      highly promiscuous, with J values between 0.72 and 0.92; GST A4-4, involved in
      the clearance of lipid peroxidation products, is moderately promiscuous (J =
      0.37). Promiscuity indices also allowed for studies of correlation between
      substrate promiscuity and an enzyme's activity toward its most-favored substrate,
      for each of the three enzyme classes.

PMID- 18081311
TI  - Catalytic properties of ADAM12 and its domain deletion mutants.
AB  - Human ADAM12 (a disintegrin and metalloproteinase) is a multidomain zinc
      metalloproteinase expressed at high levels during development and in human
      tumors. ADAM12 exists as two splice variants: a classical type 1 membrane
      anchored form (ADAM12-L) and a secreted splice variant (ADAM12-S) consisting of
      pro, catalytic, disintegrin, cysteine-rich, and EGF domains. Here we present a
      novel activity of recombinant ADAM12-S and its domain deletion mutants on S
      carboxymethylated transferrin (Cm-Tf). Cleavage of Cm-Tf occurred at multiple
      sites, and N-terminal sequencing showed that the enzyme exhibits restricted
      specificity but a consensus sequence could not be defined as its subsite
      requirements are promiscuous. Kinetic analysis revealed that the noncatalytic C
      terminal domains are important regulators of Cm-Tf activity and that ADAM12-PC
      consisting of the pro domain and catalytic domain is the most active on this
      substrate. It was also observed that NaCl inhibits ADAM12. Among the tissue
      inhibitors of metalloproteinases (TIMP) examined, the N-terminal domain of TIMP-3
      (N-TIMP-3) inhibits ADAM12-S and ADAM12-PC with low nanomolar Ki(app) values
      while TIMP-2 inhibits them with a slightly lower affinity (9-44 nM). However,
      TIMP-1 is a much weaker inhibitor. N-TIMP-3 variants that lack MMP inhibitory
      activity but retained the ability to inhibit ADAM17/TACE failed to inhibit
      ADAM12. These results indicate unique enzymatic properties of ADAM12 among the
      members of the ADAM family of metalloproteinases.

PMID- 18081312
TI  - Carbon isotope effect study on orotidine 5'-monophosphate decarboxylase: support
      for an anionic intermediate.
AB  - Orotidine 5'-monophosphate decarboxylase has been heavily examined in recent
      years due to its enzymatic proficiency, which provides a catalytic enhancement to
      a reaction rate approximately 1017 times greater than that of the nonenzymatic
      reaction. Several mechanisms proposed to explain this catalytic enhancement have
      included covalent addition, ylide or carbene formation, and most recently
      concerted protonation. All of these mechanisms have circumvented the formation of
      a high-energy vinyl anionic intermediate. To investigate the presence of an
      anionic intermediate, 13C isotope effect studies have been performed using the
      alternate substrate 5-fluoro-OMP (OMP = orotidine 5'-monophosphate). Isotope
      effects obtained for the wild-type enzyme with OMP and 5-fluoro-OMP are 1.0255
      and 1.0106, respectively, corresponding to a decrease of approximately 1.5% for 5
      fluoro-OMP. With the K59A enzyme, the intrinisic isotope effects show a similar
      decrease of approximately 1.9% from 1.0543 with OMP to 1.0356 with 5-fluoro-OMP.
      This decrease results from the inductive effect of the fluorine, which stabilizes
      the carbanion intermediate by electron withdrawal and produces a reaction with an
      earlier transition state. The isotope effect for the decarboxylation of the slow
      substrate 2'-deoxy-OMP produced a intrinsic isotope effect of nearly 1.0461.

PMID- 18081313
TI  - Structural and dynamic basis of phospholamban and sarcolipin inhibition of Ca(2+)
      ATPase.
AB  - Phospholamban (PLN) and sarcolipin (SLN) are two single-pass membrane proteins
      that regulate Ca2+-ATPase (SERCA), an ATP-driven pump that translocates calcium
      ions into the lumen of the sarcoplasmic reticulum, initiating muscle relaxation.
      Both proteins bind SERCA through intramembrane interactions, impeding calcium
      translocation. While phosphorylation of PLN at Ser-16 and/or Thr-17 reestablishes
      calcium flux, the regulatory mechanism of SLN remains elusive. SERCA has been
      crystallized in several different states along the enzymatic reaction
      coordinates, providing remarkable mechanistic information; however, the lack of
      high-resolution crystals in the presence of PLN and SLN limits the current
      understanding of the regulatory mechanism. This brief review offers a survey of
      our hybrid structural approach using solution and solid-state NMR methodologies
      to understand SERCA regulation from the point of view of PLN and SLN. These
      results have improved our understanding of the calcium translocation process and
      are the basis for designing new therapeutic approaches to ameliorate muscle
      malfunctions.

PMID- 18081314
TI  - Characterization of the substrate mimic bound to engineered prostacyclin synthase
      in solution using high-resolution NMR spectroscopy and mutagenesis: implication
      of the molecular mechanism in biosynthesis of prostacyclin.
AB  - High-resolution NMR spectroscopy was used to determine the docking of a substrate
      (prostaglandin H2) mimic (U46619) to the engineered prostacyclin (PGI2) synthase
      (PGIS) in solution. The binding of U46619 to the PGIS protein was demonstrated by
      1D NMR titration, and the significant perturbation of the chemical shifts of
      protons at C-11, H2C, and H20 of U46619 were observed upon U46619 binding to the
      engineered PGIS in a concentration-dependent manner. The detailed conformational
      change and 3D structure of the PGIS-bound U46619 were further demonstrated by 2D
      1H NMR experiments using the transferred NOE technique. The distances between the
      protons H20 and H2, H18 and H2, and H18 and H4 are shorter following their
      binding to the PGIS in solution-down to within 5 A. These shorter distances
      resulted in a widely open conformation, where the triangle shape of the unbound
      U46619 changed to a more compact conformation with an oval shape. The bound
      conformation of U46619 fits the crystal structure of the PGIS substrate binding
      pocket considerably better than that of the unbound U46619. The residues
      important to the substrate binding in the active site pocket of PGIS were also
      predicted. For example, Trp282 could be one of the most important residues and is
      suspected to play a role in the determination of specific catalytic function,
      which has been established by the docking studies using the NMR structure of the
      PGIS-bound form of U46619 and the PGIS crystal structure. These studies have
      provided the structural information for the interaction of the PGIS with its
      substrate mimic. The noted conformational changes where the C-6 position is
      closer to the C-9 position of U46619 provided the first experimental data for
      understanding the molecular mechanism of the catalytic function of PGIS in the
      isomerization of PGH2 to prostacyclin.

PMID- 18081315
TI  - Serine 23 and 36 phosphorylation of caveolin-2 is differentially regulated by
      targeting to lipid raft/caveolae and in mitotic endothelial cells.
AB  - In the present study, using a combination of reconstituted systems and
      endothelial cells endogenously expressing caveolins, we show that phosphorylation
      of caveolin-2 at serines 23 and 36 can be differentially regulated by caveolin-1
      mediated subcellular targeting to lipid raft/caveolae and in endothelial cells
      synchronized in mitosis. Detergent insolubility and sucrose flotation gradient
      experiments revealed that serine 23 phosphorylation of caveolin-2 preferably
      occurs in detergent-resistant membranes (DRMs), while serine 36 phosphorylation
      takes place in non-DRMs. Furthermore, immunofluorescence microscopy studies
      determined that in the presence of caveolin-1, serine 23-phosphorylated caveolin
      2 mostly localizes to plasma membrane, while serine 36-phosphorylated caveolin-2
      primarily resides in intracellular compartments. To directly address the role of
      caveolin-1 in regulating phosphorylation of endogenous caveolin-2, we have used
      the siRNA approach. The specific knockdown of caveolin-1 in endothelial cells
      decreases caveolin-2 phosphorylation at serine 23 but not at serine 36. Thus,
      upregulation of serine 23 phosphorylation of caveolin-2 depends on caveolin-1
      driven targeting to plasma membrane lipid rafts and caveolae. Interestingly,
      although serine 36 phosphorylation does not seem to be regulated in endothelial
      cells by caveolin-1, it can be selectively upregulated in endothelial cells
      synchronized in mitosis. The latter data suggests a possible involvement of
      serine 36-phosphorylated caveolin-2 in modulating mitosis.

PMID- 18081316
TI  - Reversible inhibition of alpha-ketoglutarate dehydrogenase by hydrogen peroxide:
      glutathionylation and protection of lipoic acid.
AB  - We have previously demonstrated that when cardiac mitochondria were challenged
      with H2O2, NADH production and oxidative phosphorylation declined. Upon
      consumption of H2O2, mitochondrial function was restored. These alterations were
      due, in large part, to reversible glutathionylation and inhibition of the Krebs
      cycle enzyme alpha-ketoglutarate dehydrogenase. The current study was undertaken
      to identify the site and consequences of alpha-ketoglutarate dehydrogenase
      glutathionylation. Mitochondria were treated with H2O2 for varying periods of
      time. Protein sulfhydryls that had undergone H2O2 mediated glutathionylation were
      specifically derivatized with N-ethylmaleimide-biotin. Subsequent purification of
      biotin labeled (glutathionylated) protein and Western blot analysis revealed that
      the E2 subunit of alpha-ketoglutarate dehydrogenase was reversibly
      glutathionylated. Further analysis revealed that lipoic acid, a required cofactor
      covalently attached to the E2 subunit, was the site of glutathionylation. The
      relative level of glutathionylated lipoic acid closely paralleled the degree of
      enzyme inhibition and reactivation. Glutathionylation of alpha-ketoglutarate
      dehydrogenase protected lipoic acid from modification by the electrophilic lipid
      peroxidation product 4-hydroxy-2-nonenal. Glutathionylation of alpha
      ketoglutarate dehydrogenase can therefore be viewed as an antioxidant response
      protecting the enzyme from oxidative damage.

PMID- 18081317
TI  - Structural arrangement and conformational dynamics of the gamma subunit of the
      Na+/K+-ATPase.
AB  - The Na+/K+-ATPase couples the chemical energy in ATP to transport Na+ and K+
      across the plasma membrane against a concentration gradient. The ion pump is
      composed of two mandatory subunits: the alpha subunit, which is the major
      catalytic subunit, and the beta subunit, which is required for proper trafficking
      of the complex to the plasma membrane. In some tissues, the ion pump also
      contains an optional third subunit, gamma, which modulates the pump activity. To
      examine the conformational dynamics of the gamma subunit during ion transport and
      its position in relation to the alpha and the beta subunits, we have used
      fluorescence resonance energy transfer under voltage clamp conditions. From these
      experiments, evidence is provided that the gamma subunit is located adjacent to
      the M2-M6-M9 pocket of the alpha subunit at the transmembrane-extracellular
      interface. We have also used fluorescence resonance energy transfer to
      investigate the relative movement of the three subunits as the ion pump shuttles
      between the two main conformational states, E1 and E2, as described by the Albers
      Post scheme. The results from this study suggest that there is no relative change
      in distance between the alpha and gamma subunits but there is a relative change
      in distance between the beta and gamma subunits during the E2 to E1 transition.
      It was also observed that labeling the gamma subunit at specific residues with
      fluorophores induces a decrease in K+-induced stationary current. This result
      could be due to a perturbation in the K+ branch of the reaction cycle of the
      pump, representing a new way to inhibit the pump.

PMID- 18081318
TI  - Hydrophobic substitutions in the first residue of the CRAC segment of the gp41
      protein of HIV.
AB  - We investigated the peptides N-acetyl-AWYIK-amide and N-acetyl-VWYIK-amide
      corresponding to single amino acid substitutions in LWYIK, a segment found in the
      gp41 protein of HIV and believed to play a role in sequestering this protein to a
      cholesterol-rich domain in the membrane. The effects of these peptides on the
      thermotropic phase transitions of 1-stearoyl-2-oleoylphosphatidylcholine (SOPC)
      and mixtures of SOPC and cholesterol were intermediate between that having the
      wild-type sequence (LWYIK) and another (IWYIK), the least active peptide
      previously studied. This correlated with results from studies of single mutations
      in the gp41 protein of HIV-1, in which L679 of the LWYIK segment is replaced with
      either A or V, measuring the capability of TZM-BL HeLa-based HIV-1 indicator
      cells to form syncytia. The peptides were also comparatively analyzed in silico.
      All together, the results suggest that the mode of interaction of this region of
      gp41 with the polar heads of membrane lipids contributes to its cholesterol
      selectivity and that this is somehow related to the biological activity of the
      viral glycoprotein.

PMID- 18081319
TI  - Suppression of microtubule dynamic instability by the +TIP protein EB1 and its
      modulation by the CAP-Gly domain of p150glued.
AB  - The EB1+TIP protein family and its binding partners track growing plus ends of
      microtubules in cells and are thought to regulate their dynamics. Here we
      determined the effects of EB1 and the N-terminal CAP-Gly domain (p150n) of one of
      its major binding partners, p150Glued, both separately and together, on the
      dynamic instability parameters at plus ends of purified steady-state
      microtubules. With EB1 alone, the shortening rate, the extent of shortening, and
      the catastrophe frequency were suppressed in the absence of significant effects
      on the growth rate or rescue frequency. The effects of EB1 on dynamics were
      significantly different when p150n was added together with EB1. The rate and
      extent of shortening and the catastrophe frequency were suppressed 3-4 times more
      strongly than with EB1 alone. In addition, the EB1-p150n complex increased the
      rescue frequency and the mean length the microtubules grew, parameters that were
      not significantly affected by EB1 alone. Similarly, deletion of EB1's C-terminal
      tail, which is a crucial binding region for p150n, significantly increased the
      ability of EB1 to suppress shortening dynamics. EB1 by itself bound along the
      length of the microtubules with 1 mol of EB1 dimer bound per approximately 12 mol
      of tubulin dimer. Approximately twice the amount of EB1 was recruited to the
      microtubules in the presence of p150n. Our results indicate that inactivation of
      EB1's flexible C-terminal tail significantly changes EB1's ability to modulate
      microtubule dynamics. They further suggest that p150Glued may activate and
      thereby facilitate the recruitment of EB1 to the tips of microtubules to regulate
      their dynamics.

PMID- 18081320
TI  - Structure and function of PA4872 from Pseudomonas aeruginosa, a novel class of
      oxaloacetate decarboxylase from the PEP mutase/isocitrate lyase superfamily.
AB  - Pseudomonas aeruginosa PA4872 was identified by sequence analysis as a
      structurally and functionally novel member of the PEP mutase/isocitrate lyase
      superfamily and therefore targeted for investigation. Substrate screens ruled out
      overlap with known catalytic functions of superfamily members. The crystal
      structure of PA4872 in complex with oxalate (a stable analogue of the shared
      family alpha-oxyanion carboxylate intermediate/transition state) and Mg2+ was
      determined at 1.9 A resolution. As with other PEP mutase/isocitrate lyase
      superfamily members, the protein assembles into a dimer of dimers with each
      subunit adopting an alpha/beta barrel fold and two subunits swapping their
      barrel's C-terminal alpha-helices. Mg2+ and oxalate bind in the same manner as
      observed with other superfamily members. The active site gating loop, known to
      play a catalytic role in the PEP mutase and lyase branches of the superfamily,
      adopts an open conformation. The Nepsilon of His235, an invariant residue in the
      PA4872 sequence family, is oriented toward a C(2) oxygen of oxalate analogous to
      the C(3) of a pyruvyl moiety. Deuterium exchange into alpha-oxocarboxylate
      containing compounds was confirmed by 1H NMR spectroscopy. Having ruled out known
      activities, the involvement of a pyruvate enolate intermediate suggested a
      decarboxylase activity of an alpha-oxocarboxylate substrate. Enzymatic assays led
      to the discovery that PA4872 decarboxylates oxaloacetate (kcat = 7500 s(-1) and
      Km = 2.2 mM) and 3-methyloxaloacetate (kcat = 250 s(-1) and Km = 0.63 mM). Genome
      context of the fourteen sequence family members indicates that the enzyme is used
      by select group of Gram-negative bacteria to maintain cellular concentrations of
      bicarbonate and pyruvate; however the decarboxylation activity cannot be
      attributed to a pathway common to the various bacterial species.

PMID- 18081321
TI  - Aquaporin 0-calmodulin interaction and the effect of aquaporin 0 phosphorylation.
AB  - Aquaporin 0 (AQP0), also known as major intrinsic protein of lens, is the most
      abundant membrane protein in the lens and it undergoes a host of C-terminally
      directed posttranslational modifications. The C-terminal region containing the
      major phosphorylation sites is a putative calmodulin-binding site, and calmodulin
      has been shown to regulate AQP0 water permeability. The purpose of the present
      study was to elucidate the role of AQP0 phosphorylation on calmodulin binding.
      AQP0 C-terminal peptides were synthesized with and without serine phosphorylation
      on S231 and S235, and the ability of these peptides to bind dansyl-labeled
      calmodulin and the calcium dependence of the interaction was assessed using a
      fluorescence binding assay. The AQP0 C-terminal phosphorylated peptides were
      found to have 20-50-fold lower affinities for calmodulin than the
      unphosphorylated peptide. Chemical cross-linking studies revealed specific sites
      of AQP0-calmodulin interaction that are significantly reduced by AQP0
      phosphorylation. These data suggest that AQP0 C-terminal phosphorylation affects
      calmodulin binding in vivo and has a role in regulation of AQP0 function.

PMID- 18081323
TI  - Conformational and noncovalent complexation changes in proteins during
      electrospray ionization.
AB  - Electrospray ion sources efficiently produce gas-phase ions from proteins and
      their noncovalent complexes. Charge-state distributions of these ions are
      increasingly used to gauge their conformations in the solution phase. Here we
      investigate how this correlation is affected by the spraying conditions at the
      early stage of droplet generation, prior to the ionization process. We followed
      the folding behavior of model proteins cytochrome c and ubiquitin and the
      dissociation of the noncovalent holomyoglobin complex. Spray current
      measurements, fast Taylor cone imaging, and mass analysis of the generated ions
      indicated that the protein structure experienced conformational or complexation
      changes upon variations in the spraying mode of the electrospray ionization
      source. These effects resulted in a departure from the original secondary,
      tertiary, and quaternary structure of proteins, possibly introducing artifacts in
      related studies. Therefore, if a particular gas-phase ion conformation is
      required or correlations with the liquid-phase conformations are studied, it is
      advantageous to maintain a particular spraying mode. Alternatively, spraying mode
      induced changes can be utilized to alter the structure of proteins in, for
      example, time-resolved experiments for the study of protein folding dynamics.

PMID- 18081322
TI  - Chemical interplay in the mechanism of partial agonist activation in alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.
AB  - Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, one
      subtype in the family of ionotropic glutamate receptors, are the main receptors
      responsible for excitatory signaling in the mammalian central nervous system.
      Previous studies utilitizing the isolated ligand binding domain of these
      receptors have provided insight into the role of specific ligand-protein
      interactions in mediating receptor activation. However, these studies relied
      heavily on the partial agonist kainate, in which the alpha-amine group is
      constrained in a pyrrolidine ring. Here we have studied a series of substituted
      and unsubstituted willardiines with primary alpha-amine groups similar to that of
      the full agonist glutamate whose activation can be varied depending on the size
      of the substituent. The specific ligand-protein interactions in the mechanism of
      partial agonism in this subtype were investigated using vibrational spectroscopy,
      and the large-scale conformational changes in the ligand binding domain were
      studied with fluorescence resonance energy transfer (FRET). These investigations
      show that the strength of the interaction at the alpha-amine group correlates
      with the extent of cleft closure and extent of activation, with the agonist of
      higher efficacy showing larger cleft closure and stronger interactions at this
      group, suggesting that this is one of the mechanisms by which the agonist
      controls receptor activation.

PMID- 18081324
TI  - TOF-SIMS and principal component analysis characterization of the multilayer
      surface grafting of small molecules: antibacterial furanones.
AB  - Furanone compounds (fimbrolides) have attracted interest as antibacterial
      compounds for use in human health care, for instance, as an antibacterial coating
      for medical devices to combat device-centered infections. To ensure effectiveness
      for extended periods of time, they must be immobilized covalently onto a device
      surface; in this study, this was done via azide/nitrene chemistry and
      photochemical coupling. However, the detection and quantification of surface
      immobilized small molecules such as furanones presents a considerable analytical
      challenge, yet is necessary for optimization of coatings and reliable
      interpretation of biological responses. We have utilized the surface sensitivity
      and chemical specificity of time-of-flight secondary ion mass spectrometry (TOF
      SIMS) to characterize each step of the grafting sequence. On account of the
      complexity of the data, principal component analysis (PCA) was used to interpret
      and compare spectra. The results demonstrate the utility of TOF-SIMS with PCA for
      the detection of the surface-grafted small molecules azidoaniline and a
      brominated furanone; imaging of the bromine ion peaks also enabled assessment of
      grafting uniformity. Thus, successful multilayer coating and furanone grafting
      was observed, and substantial and uniform coverage of furanone molecules on the
      surface. Even multiple grafting steps involving, in the present case, two low
      molecular weight compounds can readily be disentangled by PCA. The utility of TOF
      SIMS analysis with PCA is particularly well illustrated in the present case by
      the grafting of the furanone molecules, which did not yield a singular unique
      peak in the positive ion mass spectra, whereas the collective spectral changes
      elucidated by PCA provided unambiguous verification of successful grafting of
      this low molecular weight compound.

PMID- 18081325
TI  - Characterization of polar compounds and oligomers in secondary organic aerosol
      using liquid chromatography coupled to mass spectrometry.
AB  - A generic method has been developed for the analysis of polar compounds and
      oligomers in secondary organic aerosol (SOA) formed during atmospheric simulation
      chamber experiments. The technique has been successfully applied to SOA formed in
      a variety of systems, ranging from ozonolysis of biogenic volatile organic
      compounds to aromatic photooxidation. An example application of the method is
      described for the SOA produced from the reaction of ozone with cis-3-hexenyl
      acetate, an important biogenic precursor. A range of solvents were tested as
      extraction media, and water was found to yield the highest recovery. Extracts
      were analyzed using reversed-phase liquid chromatography coupled to ion trap mass
      spectrometry. In order to determine correct molecular weight assignments and
      increase sensitivity for less polar species, a series of low-concentration mobile
      phase additives were used (NaCl, LiBr, NH4OH). Lithium bromide produced better
      fragmentation patterns, with more structural information than in the other cases
      with no reduction in sensitivity. The main reaction products identified in the
      particle-phase were 3-acetoxypropanal, 3-acetoxypropanoic acid, and 3
      acetoxypropane peroxoic acid and a series of dimers and trimers up to 500 Da.
      Structural identification of oligomers indicates the presence of linear
      polyesters possibly formed via esterfication reactions or decomposition of
      peroxyhemiacetals.

PMID- 18081326
TI  - X-ray photoelectron spectrometry depth profiling of organic thin films using C60
      sputtering.
AB  - A buckminsterfullerene (C(60)) ion beam was used for X-ray photoelectron
      spectrometry depth profiling of various organic thin films. Specimens
      representing different interfaces in organic light-emitting diode devices,
      including hole-conducting poly(ethylenedioxythiophene), poly(styrenesulfonic
      acid) (PEDOT:PSS) thin films on ITO with and without polysilicic acid doping,
      light-emitting Ir-containing 4,4'-bis(carbazol-9-yl)biphenyl (CBP) molecules on
      PEDOT:PSS, and electron-conducting 2,2',2' '(1,3,5-benzinetriyl)tris(1-phenyl-1-H
      benzimidazole) (TPBi) molecules on CBP, were studied. In all cases, a clear
      multilayer structure was observed. The chemical composition and elemental state
      were preserved after C(60+) ion sputtering. The sputter rate was found to
      decrease with sputtering time. This is due to the deposition of amorphous carbon
      on the surface, with the rate of implantation highly dependent on the surface
      interacting with the ion beam.

PMID- 18081328
TI  - Isotropic-to-nematic phase transition in a liquid-crystal droplet.
AB  - In this paper, we focus on the isotropic-to-nematic phase transition in a liquid
      crystal droplet. We present the results of an experiment to measure the growth of
      the nematic phase within an isotropic phase liquid-crystal droplet.
      Experimentally, we observe two primary phase transition regimes. At short time
      scales, our experimental results (R(t) approximately t0.51) show good agreement
      with a Stefan-type model of the evolution of the nematic phase within the
      isotropic phase of a liquid crystal. As time progresses, the growth of the
      nematic phase is restricted by increased confinement of the droplet boundary.
      During this stage of growth, the nematic phase grows at a slower rate of R(t)
      approximately t0.31. The slower growth at later stages might be due to a variety
      of factors such as confinement-induced latent heat reduction; a change of defect
      strength during its evolution; or interactions between the defect and the
      interface between the liquid crystal and oil or between adjacent defects. The
      presence of two growth regimes is also consistent with the molecular simulations
      of Bradac et al. (Bradac, Z.; Kralj, S.; Zumer, S. Phys. Rev. E 2002, 65, 021705)
      who identify an early stage domain regime and a late stage confinement regime.
      For the domain and confinement regimes, Bradac et al. (Bradac, Z.; Kralj, S.;
      Zumer, S. Phys. Rev. E 2002, 65, 021705) obtained growth exponents of 0.49 +/-
      0.05 and 0.25 +/- 0.05. These are remarkably close to the values 0.51 and 0.31
      observed in our experiments.

PMID- 18081329
TI  - Adhesion from tethered ligand-receptor bonds with microsecond lifetimes.
AB  - According to classical thermodynamics, biological ligand-receptor bonds should
      have a median lifetime of about 2 ms, and nearly half should have lifetimes of
      nanoseconds to microseconds. As a result, it is clear that many "weak" bonds are
      indispensable for cellular adhesion, signaling, and other critical events.
      However, the forces required to rupture such weak bonds and the adhesion they
      provide between surfaces are largely unknown because of their propensity to
      dissociate rapidly from a measuring probe. To measure such weak bond forces
      quantitatively, we followed nature's example of adhering surfaces with many weak
      ligand-receptor bonds. Analogously to how multiplicity promotes stronger adhesion
      between cellular membranes, multiple bonds created significant adhesion between
      model cellular surfaces. Specifically, we used an automated surface forces
      apparatus to measure the adhesion between complementary surfaces bearing dense
      populations of streptavidin receptors and flexible PEG tethers that each anchored
      a weakly binding ligand (HABA, or 2-(4-hydroxyphenylazo) benzoic acid). We show
      that this short-lived bond (<100 mus) leads to low forces of dissociation and
      only a small fraction being simultaneously bound. These results are significant
      because the HABA-streptavidin bond energy ( approximately 10.5kBT) is similar to
      the average found in nature (14.7kBT). The measurements exemplify how a single
      ligand-receptor bond may fall apart and rejoin many times before completing a
      cellular function yet can still exhibit strength in numbers.

PMID- 18081330
TI  - Settlement of Ulva zoospores on patterned fluorinated and PEGylated monolayer
      surfaces.
AB  - Various designs for coatings that resist the attachment of marine organisms are
      based on the concept of "ambiguous" surfaces that present both hydrophobic and
      hydrophilic functionalities as surface domains. In order to facilitate the
      optimal design of such surfaces, information is needed on the scale of the
      domains that the settling stages of marine organisms are able to distinguish.
      Previous experiments showed that Ulva zoospores settle (attach) in high numbers
      onto fluorinated monolayers compared to PEGylated monolayers. The main aim of the
      present study was to determine, when zoospores of the green alga Ulva are
      presented with a choice of fluorinated or PEGylated surfaces, what the minimum
      dimensions of the two types of surface are that zoospores can detect and
      consequently settle on. Silicon wafers were chemically modified to produce a
      pattern of squares containing alternating fluorinated and PEGylated stripes of
      different widths on either a uniform fluorinated or PEGylated background. Each 1
      cm x 1 cm square contained stripes with widths of 500, 200, 100, 50, 20, 5, or 2
      microm as well as an unpatterned square with a chemistry opposite that of the
      background. Spores were selective in choosing where to settle, settling at higher
      densities on fluorinated stripes compared to PEGylated stripes. However, the
      magnitude of response, and the consequences for settlement on patterned areas
      overall, was dependent on both the width of the stripes and the chemistry of the
      background. The data are discussed in relation to the ability of spores to
      "choose" favorable sites for settlement and the implications for the development
      of novel antifouling coatings.

PMID- 18081331
TI  - Patterning on nonplanar substrates: flexible honeycomb films from a range of self
      assembling star copolymers.
AB  - The effect of glass transition temperature, Tg, on the self-assembly of
      "honeycomb" microstructures on nonplanar substrates was probed by the synthesis
      of a library of core cross-linked star polymers with different arm compositions.
      Star polymers based on poly(dimethyl siloxane), poly(ethyl acrylate), poly(methyl
      acrylate), poly(tert-butyl acrylate), and poly(methyl methacrylate) were
      synthesized by the "arm first" strategy using atom-transfer radical
      polymerization. Reaction conditions were optimized, and a series of high
      molecular weight star polymers were prepared in high yield. The glass transition
      temperature of the star polymers ranged from -123 to 100 degrees C which allowed
      the suitability for the formation of porous honeycomb-like films via the "breath
      figure" technique on nonplanar surfaces to be investigated. All star compositions
      successfully formed ordered films on flat surfaces. However, only star polymer
      compositions with a Tg below 48 degrees C could form homogeneous honeycomb
      coatings on the surface of nonplanar substrates.

PMID- 18081332
TI  - Preparation of gold-tellurium hybrid nanomaterials for surface-enhanced Raman
      spectroscopy.
AB  - We report a simple method for preparing three different SERS-active substrates.
      Concentrated hydrazine solution as the reducing agent and tellurium dioxide as
      the precursor were used to prepare Te nanowires (NWs). The as-prepared Te NWs
      have an average length of 547.7 +/- 111.6 nm and an average width of 15.1 +/- 2.7
      nm. Through the reaction of Te NWs with sodium tetrachloroaurate in the presence
      of hexadecyltrimethylammonium bromide (CTAB) over reaction times of 10, 20, and
      60 min, gold-tellurium nanodumbbells, gold-tellurium nanopeapods, and gold pearl
      necklace nanomaterials (Au PNNs) were obtained, respectively. By controlling the
      reaction time, the distance between adjacent gold nanoparticles (Au NPs) in each
      Te nanowire was tunable, allowing us to investigate its effect on the SERS
      signals. Having shorter distances among Au NPs (greater electromagnetic fields),
      the Au PNNs provided a reproducible enhancement factor of 5.6 x 10(9).

PMID- 18081333
TI  - A photopatternable silicone for biological applications.
AB  - We show the application of a commercially available photopatternable silicone
      (PPS) that combines the advantageous features of both PDMS and SU-8 to address a
      critical bioMEMS materials deficiency. Using PPS, we demonstrate the ability to
      pattern free-standing mechanically isolated elastomeric structures on a silicon
      substrate: a feat that is challenging to accomplish using soft lithography-based
      fabrication. PPS readily integrates with many cell-based bioMEMS since it
      exhibits low autofluorescence and cells easily attach and proliferate on PPS
      coated substrates. Because of its inherent photopatternable properties, PPS is
      compatible with standard microfabrication processes and easily aligns to complex
      featured substrates on a wafer scale. By leveraging PPS' unique properties, we
      demonstrate the design of a simple dielectrophoresis-based bioMEMS device for
      patterning mammalian cells. The key material properties and integration
      capabilities explored in this work should present new avenues for exploring
      silicone microstructures for the design and implementation of increasingly
      complex bioMEMS architectures.

PMID- 18081334
TI  - Highly stable foams from block oligomers synthesized by enzymatic reactions.
AB  - We have synthesized a new amphiphilic block oligomer by the enzymatic linking of
      a fatty acid (lauric acid) to a fructan oligomer (inulin) and tested the
      functionality of this carbohydrate derivative in foam stabilization. The
      structure of the modified oligosaccharide was found to be (Fruc)n(Glc)1CO-C11H23,
      which implies that on average one lauric acid molecule was linked to one inulin
      molecule. The new component produces foams with exceptional stability. Our
      results show that enzymatic acylation can produce an entirely new class of
      amphiphilic materials, with functionality comparable to that of synthetic block
      copolymers.

PMID- 18081335
TI  - Umbrella sampling of solute vibrational line shifts in mixed quantum-classical
      molecular dynamics simulations.
AB  - An umbrella sampling approach for vibrational frequency line shifts is presented.
      The technique allows for efficient sampling of the solvent configurations
      corresponding to frequency shifts of a solute in mixed quantum-classical
      simulations. The approach is generally applicable and can also be used within
      traditional perturbation theory calculations of frequency shifts. It is
      particularly useful in the extraction of detailed mechanistic information about
      the solute-solvent interactions giving rise to the frequency shifts. The method
      is illustrated by application to the simple I2 in a liquid Xe system, and the
      advantages are discussed.

PMID- 18081336
TI  - Electron-transfer reactions in supercritical water.
AB  - Free energies and dynamics of electron-transfer reactions for a diatomic donor
      acceptor complex in ambient and supercritical water are studied via molecular
      dynamics computer simulations using a two-state electronic description. The free
      energy perturbation method is employed to examine diabatic electronic curves
      relevant to charge separation and recombination and electron self-exchange. It is
      found that the diabatic curves are anharmonic and vary with the charge
      distributions of the donor-acceptor complex, consonant with earlier studies under
      ambient conditions. Nonetheless, the extent of their anharmonicity and dependence
      on charge distributions grows with decreasing solvent density so that the Marcus
      free energy relationship breaks down in low-density supercritical water. The
      influence of solvent dynamics associated with activation, deactivation, and
      adiabatic barrier crossing on reaction kinetics is analyzed. Although the
      transition state theory generally provides a reasonable framework to describe
      electron-transfer kinetics in a wide range of thermodynamic conditions, the
      deviation of the reaction rate from the transition state theory predictions
      increases as the water density decreases.

PMID- 18081337
TI  - Canonical variational transition-state theory study of the CF3CH2CH3 + OH
      reaction.
AB  - Variational transition-state theory rate constants with multidimensional
      tunneling contributions using the small curvature method have been calculated for
      the CF3CH2CH3 (HFC-263fb) + OH reaction over a temperature range from 200 to 373
      K. The mPW1B95-41.0 hybrid functional, parametrized by Albu and Swaminathan to
      generate theoretical rate constants nearly identical to the experimental values
      for the CH3F + OH reaction, has been used in conjunction with the 6-31+G** basis
      set to explore the potential energy surface of the title reaction. The good
      agreement found between theoretical predictions and the experimental data
      available suggests that the present approach is an excellent option to obtain
      high-quality results at low computational cost for direct dynamics studies of
      hydrogen abstraction reactions from complex hydrofluorocarbons. The reliability
      of the structure activity relationship used to estimate rate constant values for
      OH reactions with hydrofluorocarbons is also discussed in detail.

PMID- 18081338
TI  - Interaction of ethylene oxide-propylene oxide copolymers with ionic surfactants
      studied by calorimetry: random versus block copolymers.
AB  - The present study used calorimetric techniques to follow the interaction of
      random and block ethylene oxide (EO)-propylene oxide (PO) copolymers with ionic
      surfactants. Features such as the intensity of the interaction (evaluated through
      their critical aggregation concentrations) and the profile of the isothermal
      titration calorimetry (ITC) curves were comparatively analyzed for random and
      block copolymers with similar composition (number of EO and PO units). Random
      copolymers displayed an interaction similar to that observed with other
      hydrophilic homopolymers with the additional characteristic that the intensity of
      the interaction increased with the increase in the copolymer hydrophobicity (as
      determined by its PO content), revealing that these copolymers display an
      intermediate behavior between PEO and PPO. For nonaggregated block copolymers
      (unimers) with large enough EO blocks (molar mass above 2000 g mol-1), ITC curves
      revealed that the anionic surfactant sodium dodecylsulfate (SDS) interacts with
      the PO and EO blocks almost independently, being more favorable with the PO
      block, which controls the critical aggregation concentration (cac) value. Effects
      of temperature and of the nature of the ionic surfactants on their interaction
      with these copolymers were found to agree with the previously reported trends.

PMID- 18081339
TI  - Optimizing conical intersections without derivative coupling vectors: application
      to multistate multireference second-order perturbation theory (MS-CASPT2).
AB  - We introduce a new method for optimizing minimal energy conical intersections
      (MECIs), based on a sequential penalty constrained optimization in conjunction
      with a smoothing function. The method is applied to optimize MECI geometries
      using the multistate formulation of second-order multireference perturbation
      theory (MS-CASPT2). Resulting geometries and energetics for conjugated molecules
      including ethylene, butadiene, stilbene, and the green fluorescent protein
      chromophore are compared with state-averaged complete active space self
      consistent field (SA-CASSCF) and, where possible, benchmark multireference single
      and double-excitation configuration interaction (MRSDCI) optimizations. Finally,
      we introduce the idea of "minimal distance conical intersections", which are
      points on the intersection seam that lie closest to some specified geometry such
      as the Franck-Condon point or a local minimum on the excited state.

PMID- 18081340
TI  - Reactivity of superoxide anion radical with a perchlorotriphenylmethyl (trityl)
      radical.
AB  - The reaction of superoxide radical with a tricarboxylate derivative of
      perchlorotriphenylmethyl radical (PTM-TC) is studied. PTM-TC is a stable
      ("inert") free radical, which gives a single sharp electron paramagnetic
      resonance (EPR) peak in aqueous solutions. PTM-TC also gives a characteristic
      optical absorption at 380 nm. Superoxide, on reaction with PTM-TC, induced a
      decrease in the intensity of the EPR signal and optical absorption of PTM-TC at
      380 nm. The signal loss was specific to superoxide and linearly dependent on the
      superoxide flux in the system. Competitive kinetics experiments revealed that PTM
      TC reacts with superoxide with an apparent second-order rate constant of
      8.3x10(8) M(-1) s(-1). Electrochemical and mass spectrometric analyses of the
      reaction suggested the formation of perchlorotriphenylmethane and molecular
      oxygen as products. The high sensitivity of detection of PTM-TC combined with the
      high rate constant of the reaction of superoxide with PTM-TC may offer a
      potential opportunity for measurement of superoxide in biological systems. In
      conclusion, the PTM-TC molecule has high sensitivity and specificity for
      superoxide radicals and thus may enable quantitative detection of superoxide
      generation in biological systems using EPR and/or spectrophotometric methods.

PMID- 18081341
TI  - Phonon-driven exciton dissociation at donor-acceptor polymer heterojunctions:
      direct versus bridge-mediated vibronic coupling pathways.
AB  - We present a molecular-level, quantum dynamical analysis of phonon-driven exciton
      dissociation at polymer heterojunctions, using a linear vibronic coupling model
      parametrized for 3 electronic states and 24 vibrational modes. Quantum dynamical
      simulations were carried out using the multiconfiguration time-dependent Hartree
      method. In this study, which significantly extends the two-state model of Tamura
      et al. (Tamura, H.; Bittner, E. R.; Burghardt, I. J. Chem. Phys. 2007, 126,
      021103), we focus on the role of bridge states, which can mediate the decay of
      the photogenerated exciton and possibly interfere with the direct transition
      toward an interfacial charge-separated state. Both the direct and bridge-mediated
      pathways are found to depend critically on the dynamical interplay of high
      frequency C=C stretch modes and low-frequency ring-torsional modes. The dynamical
      mechanism is interpreted in terms of a hierarchical electron-phonon model,
      leading to the identification of generalized reaction coordinates for the
      nonadiabatic process. Variation of the vibronic coupling model parameters in a
      realistic range provides evidence that the direct exciton decay pathway is not
      dynamically robust, and bridge-mediated pathways can become dominant. The
      ultrafast, coherent dynamics is of pronounced nonequilibrium character and cannot
      be modeled by conventional kinetic equations. The predicted femtosecond to
      picosecond decay times are consistent with time-resolved spectroscopic
      observations.

PMID- 18081343
TI  - Synthesis and properties of oligonucleotides with iodo-substituted aromatic
      aglycons: investigation of possible halogen bonding base pairs.
AB  - Ab initio calculations of halogen bond energies of artificial base pairs
      constructed between iodinated aromatic nucleobase mimics and nitrogen-containing
      acceptor molecules such as pyridine and imidazole suggest that modified base
      pairs are converted to optimized planar base pairs with weak Delta E values of 
      0.19 to -3.93 kcal/mol. To evaluate the contribution of halogen bonding toward
      duplex stabilization of such modified nucleobase mimics introduced into
      artificial base pairs, we synthesized three C-nucleoside analogues 1-3 with
      several iodinated aromatic rings and an imidazole nucleoside derivative 4 and
      incorporated them into oligodeoxynucleotides. Hybridization studies of modified
      oligodeoxynucleotides incorporating iodoaromatic bases showed their unique
      universal base-like ability; however, no indication of halogen bond formation was
      observed. A more sophisticated design is required for the development of new base
      pairs stabilized by halogen bonding.

PMID- 18081344
TI  - A simple helical macrocyclic polyazapyridinophane as a stereoselective receptor
      of biologically important dicarboxylates under physiological conditions.
AB  - The interaction of a synthetic enantiopure azamacrocyclic receptor (L) with
      biologically important chiral dicarboxylates (A, 1-7) has been studied by means
      of potentiometric titrations in 0.15 M NaCl aqueous solution in a wide pH range.
      This macrocycle forms strong complexes of the type [HnLA](n-2) (with n = 0-5). As
      a general trend, the binding is much tighter at basic or neutral pH than in
      acidic medium. Interestingly, nonprotected excitatory amino acids (Asp and Glu)
      are strongly bound even at acidic pH. Regarding selectivity, the receptor showed
      stereoselective binding toward those substrates bearing an H-bonding donor at
      Calpha, being S-selective in most of the cases, except for glutamic acid. Thus, L
      displayed an excellent enantioselectivity for (S)-malate dianion (KS/KR = 11.50
      at pH 10.0 and KS/KR = 6.86 at pH 7.0) and exhibited moderate enantiopreference
      for (S,S)-tartrate (KSS/KRR = 3.01 at pH 10 and KSS/KRR = 1.70 at pH 7.0). For
      this last anion, a very good diastereopreference was also observed (KSS/KRS =
      8.46 at pH 10 and KSS/KRS = 4.99 at pH 7.0). On the contrary, L is smoothly R
      selective toward (R)-Glu (KR/KS = 3.22 at pH 10 and KR/KS = 2.05 at pH 7.0) due
      to its longer and more flexible molecular structure. The stereoselectivity of the
      corresponding complexes decreased when decreasing pH values. For the hydroxy
      derivatives, mass spectrometry also reflected the trends observed by
      potentiometry and confirmed the receptor:dicarboxylate 1:1 stoichiometry of the
      supramolecular complexes. Additional experimental techniques were used to study
      the most stereoselective example. Solution studies by NMR suggested a good
      geometrical complementarity between the malate dianion and the receptor, which
      showed a predominant helical conformation in solution. Besides, self-diffusion
      rates (PGSE) of the diastereomeric complexes with malate also agree with binding
      data. Circular dichroism was also used in this case at different pH values,
      showing a very good correlation between the helical content of the receptor and
      the stereoselectivity of the molecular recognition process.

PMID- 18081345
TI  - Characterization of the switch in the mechanism of an intramolecular Diels-Alder
      reaction.
AB  - Changing the dienophile moiety of an intramolecular Diels-Alder (IMDA)
      cycloaddition from an allyl ether to an allenyl ether can dramatically change the
      regioselectivity. We hereby show by density functional theory computations that
      such unprecedented divergence is produced by an underlying change in the
      mechanism of the reaction. The allyl ether yields a fused tetrahydrofuran through
      a classical Diels-Alder reaction, whereas the allenyl ether yields a
      (methylidene)tetrahydropyran through a stepwise process. The latter reaction
      involves an extreme asynchronism in the bond-forming events with a diradicaloid
      intermediate that is stabilized by conjugation and synergistic (captodative)
      effects. Comparison with intermolecular model D-A reactions, which are concerted
      processes with various degrees of asynchrony, helps explain the change in
      regioselectivity for the IMDA reaction of allyl systems and the shift in
      mechanism for the IMDA reaction of the allenyl derivatives studied.

PMID- 18081346
TI  - Synthesis of isotopically labeled P-site substrates for the ribosomal peptidyl
      transferase reaction.
AB  - Isotopomers of the ribosomal P-site substrate, the trinucleotide peptide
      conjugate CCA-pcb (Zhong, M.; Strobel, S. A. Org. Lett. 2006, 8, 55-58), have
      been designed and synthesized in 26-35 steps. These include individual isotopic
      substitution at the alpha-hydrogen, carbonyl carbon, and carbonyl oxygen of the
      amino acid, the O2' and O3' of the adenosine, and a remote label in the N3 and N4
      of both cytidines. These isotopomers were synthesized by coupling cytidylyl
      (3',5')-cytidine phosphoramidite isotopomers as the common synthetic
      intermediates, with isotopically substituted A-Phe-cap-biotin (A-pcb). The
      isotopic enrichment is higher than 99% for 1-13C (Phe), 2-2H (Phe), and 3,4-15N2
      (cytidine), 93% for 2'/3'-18 O (adenosine), and 64% for 1-18 O (Phe). A new
      synthesis of highly enriched [1-18 O2]phenylalanine has been developed. The
      synthesis of [3'-18 O]adenosine was improved by Lewis acid aided regioselective
      ring opening of the epoxide and by an economical SN2-SN2 method with high
      isotopic enrichment (93%). Such substrates are valuable for studies of the
      ribosomal peptidyl transferase reaction by complete kinetic isotope effect
      analysis and of other biological processes catalyzed by nucleic acid related
      enzymes, including polymerases, reverse transcriptases, ligases, nucleases, and
      ribozymes.

PMID- 18081347
TI  - 1-amino-2-phenylcyclopentane-1-carboxylic acid: a conformationally restricted
      phenylalanine analogue.
AB  - DFT calculations at the B3LYP/6-311G(d,p) level have been used to investigate the
      intrinsic conformational preferences of 1-amino-2-phenylcyclopentane-1-carboxylic
      acid (c5Phe), a constrained analogue of phenylalanine in which the alpha and beta
      carbons are included in a cyclopentane ring. Specifically, the N-acetyl-N'
      methylamide derivatives of the cis and trans stereoisomers, where cis and trans
      refer to the relative position between the amino group and the phenyl ring, have
      been calculated. Solvent effects have been examined using a self-consistent
      reaction field (SCRF) method. Results indicate that the conformational space of
      the cis stereoisomer is much more restricted than that of the trans derivative
      both in the gas phase and in solution.

PMID- 18081348
TI  - Quantitative study of interactions between oxygen lone pair and aromatic rings:
      substituent effect and the importance of closeness of contact.
AB  - Current models describe aromatic rings as polar groups based on the fact that
      benzene and hexafluorobenzene are known to have large and permanent quadrupole
      moments. This report describes a quantitative study of the interactions between
      oxygen lone pair and aromatic rings. We found that even electron-rich aromatic
      rings and oxygen lone pairs exhibit attractive interactions. Free energies of
      interactions are determined using the triptycene scaffold and the equilibrium
      constants were determined by low-temperature 1H NMR spectroscopy. An X-ray
      structure analysis for one of the model compounds confirms the close proximity
      between the oxygen and the center of the aromatic ring. Theoretical calculations
      at the MP2/aug-cc-pVTZ level corroborate the experimental results. The origin of
      attractive interactions was explored by using aromatic rings with a wide range of
      substituents. The interactions between an oxygen lone pair and an aromatic ring
      are attractive at van der Waals' distance even with electron-donating
      substituents. Electron-withdrawing groups increase the strength of the attractive
      interactions. The results from this study can be only partly rationalized by
      using the current models of aromatic system. Electrostatic-based models are
      consistent with the fact that stronger electron-withdrawing groups lead to
      stronger attractions, but fail to predict or rationalize the fact that weak
      attractions even exist between electron-rich arenes and oxygen lone pairs. The
      conclusion from this study is that aromatic rings cannot be treated as a simple
      quadrupolar functional group at van der Waals' distance. Dispersion forces and
      local dipole should also be considered.

PMID- 18081349
TI  - Facile synthesis of a "ready to use" precursor of porphobilinogen and its amino
      Acid derivatives.
AB  - A practical synthesis of porphobilinogen based on the biosynthetic mechanism is
      described. The crossed Mukayiama aldol reaction is the key step creating the
      central carbon-carbon bond between the two protected forms of 5-aminolevulinic
      acids. The optimized sequence gives a crystalline, storable precursor, which can
      be transformed in high yield into porphobilinogen and bioconjugates thereof. The
      enzymatic hydrolysis of the precursor produces porphobilinogen in quantitative
      yield.

PMID- 18081350
TI  - A reversible pH-dependent intramolecular pyridine-aldehyde cyclization.
AB  - A dipicolylamine (DPA) attached to an aldehyde moiety cyclizes to form a
      pyridinium-fused heterocycle. This intramolecular reaction between the pyridine
      and aldehyde moieties is reversible, and the position of the equilibrium is
      controlled by pH. The fused-ring heterocycle is stabilized under acidic
      conditions, whereas the ring-opened form is the major species under basic
      conditions. The ring-closed form can be utilized as a masked aldehyde precursor
      to access a variety of functional metal chelators containing the DPA unit.

PMID- 18081351
TI  - Chiral tertiary diamines in asymmetric synthesis.

PMID- 18081352
TI  - Systematic study on quantum confinement and waveguide effects for elastic and
      inelastic currents in atomic gold wire: importance of the phase factor for
      modeling electrodes.
AB  - Quantum confinement of the electrodes is an important issue for electron
      transport through molecular or atomic wire junctions. To assess the importance of
      waveguide effects by quantum confinement of the electrodes, we have calculated
      elastic and inelastic conductance and inelastic electron tunneling spectra of
      atomic gold wire with gold electrodes for several models. The results show the
      quite important role of the phase factors between the modeled electrodes and the
      contact region.

PMID- 18081353
TI  - Rayleigh-instability-induced metal nanoparticle chains encapsulated in nanotubes
      produced by atomic layer deposition.
AB  - Cu nanoparticle chains encapsulated in Al2O3 nanotubes were successfully
      generated in a controlled manner by reduction of CuO nanowires embedded in Al2O3
      at a sufficiently high temperature. The Al2O3 coating was deposited by atomic
      layer deposition (ALD). The particles mainly show a rodlike shape and are
      regularly distributed. The particle diameters and chain lengths corresponding to
      the inner diameters and lengths of the tubes, respectively, are controlled by the
      size of the CuO nanowire templates. Rayleigh instability, assisted by the uniform
      volume shrinkage created by the reduction of oxide to metal, is proposed to
      induce the formation of the nanochains. This method may potentially be extended
      to the synthesis of nanochains of other metals by reducing corresponding oxide
      nanowires embedded in ALD shells.

PMID- 18081354
TI  - Herding nanotransporters: localized activation via release and sequestration of
      control molecules.
AB  - A challenge for nanotechnology is the dynamic and specific control of
      nanomachines by the user. Molecular shuttles, consisting of cargo-binding
      microtubules propelled by surface-immobilized kinesin motor proteins, are an
      example of a nanoscale system that ideally can be selectively activated at
      programmable locations and times. Here we discuss a biomimetic solution where
      activating molecules are delivered locally via photolysis of a caged compound and
      subsequently sequestered in an enzymatic network. The controlled sequestration of
      the activator not only creates a rapid deactivation when the stimulus is removed
      but also sharpens the concentration profile of the rapidly diffusing activator.
      This improvement comes at the expense of a reduced efficiency in the utilization
      of the activator molecules, suggesting that these nanosystems are most
      efficiently addressed as a swarm rather than as individuals. Our work represents
      a step toward transferring the cellular control strategies of molecular
      activation to bionanotechnology.

PMID- 18081355
TI  - Bioequivalence following buccal and sublingual placement of fentanyl buccal
      tablet 400 microg in healthy subjects.
AB  - BACKGROUND AND OBJECTIVE: The fentanyl buccal tablet (FBT) is formulated to
      enhance the rate and extent of fentanyl absorption across the buccal mucosa. FBT
      is indicated for the management of breakthrough pain (a transient flare of pain
      on a background of chronic pain otherwise controlled by treatment with opioids)
      in patients with cancer who are already receiving and who are tolerant to opioid
      therapy for their underlying persistent cancer pain. This study assessed the
      bioequivalence of a single 400-microg dose of FBT following buccal (i.e. above a
      molar tooth between the upper gum and cheek) and sublingual (i.e. placed under
      the tongue) placement in order to provide an alternative option to patients.
      METHODS: Healthy subjects were randomized to receive one FBT 400 microg buccally
      and sublingually (with naltrexone to minimize opioid effects) in an open-label,
      crossover design. Bioequivalence, as determined from the maximum plasma drug
      concentration (C(max)) and the area under the plasma drug concentration-time
      curve from time 0 to infinity (AUC(infinity)), was established if the 90%
      confidence interval (CI) for the ratio of the means of sublingual/buccal values
      fell within the range of 0.80 to 1.25. RESULTS: Ninety subjects were enrolled (67
      men, 23 women; median age 24 years), and 78 completed the study. The criteria for
      bioequivalence were met for both C(max) and AUC(infinity) for the two sites of
      tablet placement: sublingual/buccal ratio for C(max) = 0.868 (90% CI 0.815,
      0.924); sublingual/buccal ratio for AUC(infinity) = 0.947 (90% CI 0.901, 0.995).
      Buccal and sublingual placement resulted in similar values for both AUC from time
      0 to t(max') (AUC(tmax')), where t(max') is the median time to C(max) of a single
      400-microg dose of FBT administered buccally (mean [SD]: 0.35 [0.16] ng . h/mL
      buccal; 0.35 [0.16] ng . h/mL sublingual) and for time to C(max) (median [range]:
      0.75 [0.33-3.13] hours buccal; 0.78 [0.17-3.00] hours sublingual). FBT was
      generally well tolerated following placement at both sites in healthy volunteers
      administered naltrexone. CONCLUSION: The results of this study support sublingual
      FBT placement as a viable alternative to buccal placement in patients who may
      require an alternate administration site.

PMID- 18081356
TI  - Virological response in patients with hepatitis C virus genotype 1b and a high
      viral load: impact of peginterferon-alpha-2a plus ribavirin dose reductions and
      host-related factors.
AB  - BACKGROUND AND OBJECTIVE: In Japan the prevalence of the hepatitis C virus (HCV)
      antibody is highest in the elderly population. Therefore, it is important for
      elderly patients to undergo interferon (IFN) therapy. In patients with HCV
      genotype 1b and a high viral load, the sustained virological response (SVR) rate
      is lower in older compared with younger patients receiving combination antiviral
      therapy. In addition, inadequate adherence to combination therapy is often seen
      in elderly patients, and is associated with reduced response rates. The aim of
      this retrospective analysis was to evaluate the effects of host-related factors
      (i.e. sex, age, baseline HCV RNA level, bodyweight and fibrosis stage) and
      peginterferon (PEG IFN)-alpha-2a plus ribavirin dose reductions on SVR rates.
      METHODS: A total of 192 treatment-naive patients with a HCV genotype 1b infection
      and a high viral load were included in the analysis. Patients had been enrolled
      into a phase III trial of 48 weeks of treatment with PEG IFN-alpha-2a plus
      ribavirin or PEG IFN-alpha-2a plus placebo. All patients were evaluated for
      effect of drug exposure on SVR. In addition, the impact of host-related factors
      or dose reductions on SVR was assessed. RESULTS: Approximately 30% of patients
      were considered elderly (> or =60 years of age). The overall SVR rate was
      significantly higher in patients treated with combination therapy versus
      monotherapy (59.4% vs 24.0%, p < 0.001). Attainment of an SVR following
      combination therapy was not influenced by any factor evaluated in the analysis,
      although elderly males were associated with decreased SVR rates. Younger age
      (odds ratio [OR] 1.081; 95% CI 1.125, 1.034; p = 0.0009), lower baseline HCV RNA
      levels (OR 1.003; 95% CI 1.006, 1.001; p = 0.006) and a severe fibrosis stage
      (F3/4) [OR 6.194; 95% CI 1.037, 37.000; p = 0.0455] significantly increased the
      likelihood of achieving an SVR with monotherapy. In the combination therapy
      group, patients maintaining a full dosage schedule of PEG IFN-alpha-2a and
      ribavirin and those requiring dose reductions of either study drug had similar
      SVR rates (64.5% vs 61.9%). However, the SVR rate was reduced to 33.3% among
      patients who discontinued combination therapy. Three out of the 31 patients who
      received the full dosage schedule were elderly patients. In addition, of the 15
      patients who discontinued combination therapy, three were <50 years of age and
      six were > or =60 years of age. The SVR rate was reduced in patients with
      cumulative PEG IFN-alpha-2a and ribavirin doses of <60%; the majority of these
      patients were elderly. CONCLUSION: The attainment of an SVR following PEG IFN
      alpha-2a plus ribavirin combination therapy was not influenced by any of the host
      related factors evaluated in this analysis, although elderly males were
      associated with a decreased SVR rate. Younger age, male sex and lower baseline
      HCV RNA levels significantly increased the likelihood of achieving an SVR with
      monotherapy. In addition, dose reductions appeared to have a negative impact on
      SVR in elderly patients. Therefore, it is important to minimize PEG IFN-alpha-2a
      and ribavirin dose reductions by effectively managing treatment-related adverse
      events in elderly patients.

PMID- 18081357
TI  - Secondary pulmonary hypertension: haemodynamic effects of torasemide versus
      furosemide.
AB  - BACKGROUND AND OBJECTIVE: Experimental data have demonstrated controversial
      results regarding loop diuretics and their influence on the pulmonary
      vasculature. The aim of this pilot study was to compare the effect of torasemide
      versus furosemide on systemic and pulmonary haemodynamics in patients with
      secondary pulmonary hypertension. METHODS: Twenty-one patients were enrolled in
      this double-blind, randomized trial: the furosemide group (n = 11) received 40 mg
      intravenously (IV) and 80 mg orally whereas the torasemide group (n = 10)
      received 20 mg IV and 20 mg orally. Haemodynamic variables were documented and
      endothelin-1 and arterial angiotensin-II plasma levels were simultaneously
      analysed at baseline (T0), 5 minutes after IV administration (T1), at baseline
      prior to oral administration (T2), and 60 minutes after oral administration (T3).
      RESULTS: Cardiac output (relative treatment effect over time between groups; p =
      0.03) increased significantly in the torasemide group compared with the
      furosemide group. In the furosemide group, a significant increase in arterial
      angiotensin-II (AT-II) plasma levels was observed compared with the torasemide
      group (relative treatment effect over time between groups; p = 0.031).
      CONCLUSION: Torasemide increased cardiac output (relative treatment effect over
      the time), whereas treatment with furosemide significantly increased arterial AT
      II plasma levels. A possible explanation for these findings might be activation
      of the renin-angiotensin system by furosemide. However, the underlying
      pathomechanism remains to be established and evidence from an adequately powered
      trial is needed to determine if furosemide aggravates cardiac function by
      increasing AT-II plasma levels.

PMID- 18081358
TI  - Prevention of propofol-induced injection pain by sufentanil: a placebo-controlled
      comparison with remifentanil.
AB  - BACKGROUND AND OBJECTIVE: Propofol produces anaesthesia with rapid recovery but
      also causes pain or discomfort on injection. The effect of remifentanil in
      prevention of propofol-induced injection pain has been demonstrated in earlier
      studies. However, sufentanil, an opioid analgesic, has not been evaluated as an
      agent for managing pain on injection of propofol. In this study we aimed to
      compare the efficacy of remifentanil and sufentanil for the prevention of
      propofol-induced pain. METHODS: This double-blind, placebo-controlled clinical
      study was carried out from July 2006 to February 2007, and included patients who
      were candidates for elective surgery in a university hospital. From 92 American
      Society of Anesthesiologists (ASA) status I-II adult patients, 80 were randomly
      assigned to four groups of 20 each. Patients received 2 mL of sufentanil 0.01 mg,
      2 mL of remifentanil 0.01 mg, 2 mL of remifentanil 0.02 mg, or 2 mL of saline 60
      seconds prior to administration of 5 mL of propofol 1%. Patients were asked prior
      to losing consciousness whether they felt any pain due to propofol injection, and
      their pain scores were evaluated on the four-point scale of Ambesh et al.
      RESULTS: The incidence of pain was significantly lower in the remifentanil 0.02
      mg group, remifentanil 0.01-mg group and sufentanil group compared with the
      saline group (40%, 70%, 75% and 100%, respectively, p < 0.05). Median pain
      intensity scores were significantly lower in the group receiving remifentanil
      0.02 mg than in the sufentanil group (0 and 1 respectively, p < 0.05). The median
      intensity of propofol-induced pain was statistically similar between the groups
      receiving sufentanil or remifentanil 0.01 mg and the placebo group (1, 1 and 1,
      respectively, p > 0.05). CONCLUSION: Remifentanil 0.02 mg administered over 60
      seconds before propofol administration is more effective than sufentanil 0.01 mg,
      remifentanil 0.01 mg or placebo administered 1 minute prior to propofol in
      reducing the incidence and intensity of injection pain.

PMID- 18081359
TI  - Post-Hoc analysis of a head-to-head hyaluronic acid comparison in knee
      osteoarthritis using the 2004 OMERACT-OARSI responder criteria.
AB  - BACKGROUND AND OBJECTIVE: Several intra-articular hyaluronic acid products are
      available for treating osteoarthritis (OA) of the knee, including hylan G-F 20
      and the bioengineered straight-chain hyaluronic acid (Bio-HA). A recently
      published study in patients with knee OA demonstrated non-inferiority with regard
      to efficacy, using the pain subscore of the Western Ontario and McMaster
      Universities Osteoarthritis Index (safety data favoured Bio-HA with regard to
      knee effusions). However, the Osteoarthritis Research Society International
      (OARSI) Standing Committee for Clinical Trials Response Criteria Initiative
      together with the Outcome Measures in Rheumatology (OMERACT) committee have
      published new response criteria for OA clinical trials. These criteria focus on
      change in pain and physical function. The aim of this study was to reanalyse the
      data from the original comparative study of hylan G-F 20 and Bio-HA in knee OA
      utilising the new OMERACT-OARSI response criteria. METHODS: The original study
      was a prospective, multicentre, randomized, double-blind trial of 321 patients
      with knee OA who received hylan G-F 20 or Bio-HA via three intra-articular
      injections 1 week apart. This post-hoc analysis of the data using the modified
      OMERACT-OARSI responder criteria focused only on efficacy. RESULTS: Using the
      OMERACT-OARSI criteria, 112 of the 157 patients (71%) receiving Bio-HA were
      considered to have a response compared with 99 of the 158 patients (63%)
      receiving hylan G-F 20 (p = 0.10). CONCLUSIONS: Application of the new,
      standardized definition of a responder in OA clinical trials to the existing data
      reinforces that Bio-HA is non-inferior to hylan G-F 20 for knee OA. Both agents
      were similarly well tolerated, but Bio-HA was associated with a lower incidence
      of effusions, suggesting that Bio-HA has an improved risk-benefit profile
      compared with hylan G-F 20.

PMID- 18081360
TI  - Lack of bioequivalence between two aciclovir tablets in healthy subjects.
AB  - OBJECTIVE: This study aimed to compare the systemic bioavailability of two
      aciclovir tablets, Rouz-Aciclovir (test) and Zovirax (reference), in 12 healthy
      volunteers. METHODS: In a crossover design, each subject received a single oral
      dose of aciclovir 400 mg followed by a 7-day washout period. Plasma
      concentrations of aciclovir were measured for up to 12 hours using a validated
      high-performance liquid chromatography method with a lower limit of
      quantification of 50 microg/L. RESULTS: The mean values of maximum plasma
      concentration (C(max)), time to C(max) (t(max)), area under the plasma
      concentration-time curve from time 0 to 12 hours (AUC(12)) and from time 0 to
      infinity (AUC(infinity)), and plasma half-life following administration of the
      test product were 999.6 microg/L, 2.08 h, 4911.2 microg/L . h, 5417.7 microg/L .
      h and 3.08 h, respectively, and for the reference product 775.8 microg/L, 2.58 h,
      3862.1 microg/L . h, 4295.4 microg/L . h and 3.14 h, respectively. The
      test/reference geometric ratio for C(max) (90% CI) was 1.30 (97.1, 174.8). The
      test/reference geometric ratios for AUC(12) (90% CI) and AUC(infinity) (90% CI)
      were 1.26 (99.7, 159.1) and 1.24 (98.9, 155.6), respectively. Therefore, the 90%
      CIs of C(max), AUC(12) and AUC(infinity) were not within the acceptable range of
      80 and 125 suggested by the US FDA bioequivalence guideline. CONCLUSION: The
      results of the present study suggest that the aciclovir test product was not
      bioequivalent to the reference product. The exact reasons for this remain to be
      determined. However, we think the difference should be attributed to the
      difference in the type and amounts of ingredients used in the formulation that
      probably affect the contact time of aciclovir with the sites of absorption in the
      gut.

PMID- 18081361
TI  - Cost-effectiveness analysis of the addition of rituximab to CHOP in young
      patients with good-prognosis diffuse large-B-cell lymphoma.
AB  - BACKGROUND AND OBJECTIVE: Diffuse large-B-cell lymphoma (DLBCL) is an aggressive
      form of lymphoma. It accounts for 30-40% of all new cases of non-Hodgkin's
      lymphoma and is the subtype with the highest overall incidence. Before the
      development of monoclonal antibodies, the standard treatment of newly diagnosed
      DLBCL was based on combination therapy with cyclophosphamide, doxorubicin,
      vincristine and prednisone (CHOP). Current treatment consists of the combination
      of CHOP and the monoclonal antibody rituximab (R-CHOP regimen), with recovery
      rates of 70%. The aim of this study was to compare the efficacy (survival) and
      direct medical costs of two chemotherapy regimens, R-CHOP and CHOP, in the
      treatment of DLBCL in young patients with a good prognosis. METHODS: A decision
      analysis model with tree structure was used to compare R-CHOP and CHOP in the
      treatment of young patients with DLBCL from the perspective of the Italian
      National Health Service. Patients entered at the root of the tree and followed
      one of the six possible therapeutic pathways. After receiving one of the two
      chemotherapy treatments (R-CHOP or CHOP) for 5 months, patients could have a
      complete response or not. In the presence of no response, patients underwent
      rescue therapy. In the case of relapse after 3 years' follow-up (following an
      initial complete response at 5 months), patients were given rescue therapy. The
      model provided an estimate of mean survival (life-years gained [LYG]) and mean
      costs (direct medical costs) over a period of 3 years. Both survival and costs
      were discounted at a rate of 3%. Costs were in euro, year 2007 values. Several
      sensitivity analyses were carried out with varying clinical parameters. RESULTS:
      The LYG with the R-CHOP regimen was higher (2.697 LYG per patient) than with the
      CHOP regimen (2.517 LYG per patient). When taking into account the cost of rescue
      therapy, the overall mean treatment cost per patient was lower with the R-CHOP
      regimen (22,113.44 euro) than with the CHOP regimen (22,831.17 euro). Sensitivity
      analyses showed that the incremental cost-effectiveness ratios per LYG for
      complete response at 5 months (16,816.00 euro) and for relapse-free survival at 3
      years (11,967.12 euro) were below the internationally accepted threshold (50,000
      euro). Furthermore, for survival at 3 years, R-CHOP was confirmed as the dominant
      therapy (lower expected mean costs, higher number of LYG). CONCLUSIONS: Our study
      demonstrated the clinical and economic benefits of adding rituximab to a CHOP
      chemotherapy regimen in young patients who present with DLBCL with good
      prognosis. The higher costs associated with rituximab were offset by the
      significantly lower rescue therapy costs. Further studies that include patients
      with unfavourable prognosis are needed to confirm these findings.

PMID- 18081362
TI  - Gabapentin for decerebrate rigidity: a case report.
AB  - A 48-year-old woman suddenly lost consciousness as a result of a right rostral
      pontine tegmentum haemorrhage. The patient presented with decerebrate rigidity
      (DR) and regained full consciousness 5 days after the initial onset. The patient
      was given gabapentin 1200 mg/day nasogastrically and her DR significantly
      improved, although other antiepileptic drugs such as phenytoin and carbamazepine
      were given in larger dosages to decrease muscle hypertonicity. The patients'
      preserved consciousness and motor-evoked potentials to transcranial magnetic
      stimulation indicated a derangement of the extrapyramidal tracts with
      preservation of the pyramidal tracts. This case report discusses the possible
      mechanisms of action of gabapentin in DR.

PMID- 18081363
TI  - Physiological responses to exercise at altitude : an update.
AB  - Studies performed over the past decade have yielded new information related to
      the physiological and metabolic adjustments made in response to both short- and
      long-term high-altitude exposure. These investigations have examined the
      potential mechanisms responsible for the alterations observed in such key
      variables as heart rate, stroke volume, cardiac output, muscle blood flow,
      substrate utilization and mitochondrial function, both at rest and during
      exercise of varying intensities. Additionally, the occurrence and mechanisms
      related to the 'lactate paradox' continues to intrigue investigators. It is
      apparent that exposure to high altitude is an environmental stressor that elicits
      a robust sympathoadrenal response that contributes to many of the critical
      adjustments and adaptations mentioned above. Furthermore, as some of these
      important physiological adaptations are known to enhance performance, it has
      become popular to incorporate an aspect of altitude living/training into the
      training regimens of endurance athletes (e.g. 'live high-train low'). Finally, it
      is important to note that many factors influence the extent to which individuals
      adjust and adapt to the stress imposed by exposure to high altitude. Included
      among these are (i) the degree of hypoxia; (ii) the duration of exposure to
      hypoxic conditions; (iii) the exercise intensity (absolute vs relative workload);
      and (iv) the inter-individual variability in adapting to hypoxic environments
      ('responders' vs 'non-responders').

PMID- 18081364
TI  - Aspartate as an ergogenic supplement.
AB  - Aspartate has been regularly listed in exercise physiology textbooks as an
      ergogenic substance since the first known trial by Professor Henri Laborit's
      laboratory in the late 1950s, aimed at verifying its ergogenic potential. The
      main outcomes of aspartate supplementation are attenuation of exercise-induced
      hyperammonaemia and increase of exercise endurance. In the available literature,
      the impact of aspartate on endurance seems generally favourable in humans, but it
      is not so favourable in experimental animals. In studies reporting increased
      endurance, no correlation has been found between its dosage and the increment of
      exercise time. Mechanisms supposed to explain the ergogenic effect of aspartate
      have also been reviewed in this article. Claims of a glycogen-sparing action,
      reduced hyperammonaemia and a higher rate of free fatty acid oxidation have not
      been confirmed unequivocally by the literature. Aspartate has not been shown to
      increase muscle endurance or strength. It is often used in combinations that are
      briefly reviewed in this article. However, the number of studies are presently
      too low to draw conclusions about the efficacy of these aspartate combinations.
      Furthermore, as in most studies on supplements, including aspartate alone or in
      combination, it is difficult to exclude a potential publication bias against non
      significant results.

PMID- 18081365
TI  - Mobility and stability adaptations in the shoulder of the overhead athlete: a
      theoretical and evidence-based perspective.
AB  - Overhead athletes require a delicate balance of shoulder mobility and stability
      in order to meet the functional demands of their respective sport. Altered
      shoulder mobility has been reported in overhead athletes and is thought to
      develop secondary to adaptive structural changes to the joint resulting from the
      extreme physiological demands of overhead activity. Researchers have speculated
      as to whether these structural adaptations compromise shoulder stability, thus
      exposing the overhead athlete to shoulder injury. Debate continues as to whether
      these altered mobility patterns arise from soft-tissue or osseous adaptations
      within and around the shoulder. Researchers have used quantitative techniques in
      an attempt to better characterize these structural adaptations in the shoulders
      of overhead athletes. Throwing athletes have been shown to display altered
      rotational range of motion (ROM) patterns in the dominant shoulder that favour
      increased external rotation and limited internal rotation ROM. Throwers also show
      a loss of horizontal or cross-body adduction in the throwing shoulder when
      compared with the non-throwing shoulder. This posterior shoulder immobility in
      the throwing shoulder is thought by some researchers to be associated with
      reactive scarring or contracture of the periscapular soft-tissue structures (e.g.
      posterior capsule and/or cuff musculature); however, evidence of reactive
      scarring or contractures of the posterior-inferior capsule or cuff musculature
      from anatomic or noninvasive imaging studies is lacking. Conversely,
      translational ROM (laxity) has been consistently shown to be symmetric between
      dominant and non-dominant shoulders of overhead athletes. From a skeletal
      perspective, throwing shoulders are shown to have more humeral retroversion when
      compared with the non-throwing shoulder. Alterations in humeral retroversion are
      thought to develop over time in young pre-adolescent throwers when the proximal
      humeral epiphysis is not yet completely fused. Even though the evidence is
      inconclusive at the present time, there is more compelling evidence that leads us
      to believe that altered shoulder mobility in the overhead-throwing athlete is
      more strongly associated with adaptive changes in proximal humeral anatomy (i.e.
      retroversion) than to structural changes in the articular and periarticular soft
      tissue structures. In addition, this retroversion is thought to account for the
      observed shift in the arc of rotational ROM in overhead athletes. However, in
      some athletes, capsulo-ligamentous adaptations such as anterior-inferior
      stretching or posterior-inferior contracture may become superimposed upon the
      osseous changes. This may ultimately lead to pathological manifestations such as
      secondary impingement, type II superior labrum from anterior to posterior (SLAP)
      lesions and/or internal (glenoid) impingement. Overuse injuries in the overhead
      athlete are a common and perplexing clinical problem in sports medicine and,
      therefore, it is imperative for sports medicine clinicians to have a thorough
      understanding of the short- and long-term effects of overhead activity on the
      shoulder complex. It is our intention that the information presented will serve
      as a guide for clinicians who treat the shoulders of overhead athletes.

PMID- 18081366
TI  - The Yo-Yo intermittent recovery test : a useful tool for evaluation of physical
      performance in intermittent sports.
AB  - The two Yo-Yo intermittent recovery (IR) tests evaluate an individual's ability
      to repeatedly perform intense exercise. The Yo-Yo IR level 1 (Yo-Yo IR1) test
      focuses on the capacity to carry out intermittent exercise leading to a maximal
      activation of the aerobic system, whereas Yo-Yo IR level 2 (Yo-Yo IR2) determines
      an individual's ability to recover from repeated exercise with a high
      contribution from the anaerobic system. Evaluations of elite athletes in various
      sports involving intermittent exercise showed that the higher the level of
      competition the better an athlete performs in the Yo-Yo IR tests. Performance in
      the Yo-Yo IR tests for young athletes increases with rising age. The Yo-Yo IR
      tests have shown to be a more sensitive measure of changes in performance than
      maximum oxygen uptake. The Yo-Yo IR tests provide a simple and valid way to
      obtain important information of an individual's capacity to perform repeated
      intense exercise and to examine changes in performance.

PMID- 18081367
TI  - The effect of sport concussion on neurocognitive function, self-report symptoms
      and postural control : a meta-analysis.
AB  - Sport concussion is commonly assessed using a battery of tests that evaluate
      neurocognitive functioning, postural control and self-report symptoms. The degree
      to which concussion affects each of these measures is unclear. Thus, the purpose
      of this meta-analysis is to systematically review and quantify the effect of
      sport concussion on each assessment measure when administered immediately post
      injury and in the 2 weeks following injury. PubMed and PsychINFO databases were
      searched from January 1970 to June 2006, from which 39 were included for review.
      Studies were selected for review if they included concussed athletes who were
      evaluated using one of the three assessment measures. One post-morbid assessment
      must have been completed within 14 days of injury and compared with a baseline
      measure or control group. Study design, type of neurocognitive assessment, timing
      of assessment following injury and number of post-concussion assessments were
      extracted as potential moderators. Sport-related concussion had a large negative
      effect (mean Delta; 95% confidence interval) on neurocognitive functioning (
      0.81; -1.01, -0.60), self-report symptoms (-3.31; -6.35, -0.27) and postural
      control (-2.56; -6.44, 1.32) in the initial assessment following injury. A
      reduced, but large effect, was also seen in the 14 days following the initial
      assessment for neurocognitive functioning (-0.26; -0.46, -0.06), self-report
      symptoms (-1.09; -2.07, -0.11) and postural control (-1.16; -2.59, 0.27). Our
      findings demonstrated large effects for each aspect of the assessment battery.
      These findings support the use of the multifaceted concussion evaluation.

PMID- 18081368
TI  - The athlete's heart: a contemporary appraisal of the 'Morganroth hypothesis'.
AB  - As early as 1975, Morganroth and colleagues hypothesized that the cardiac
      morphological adaptation observed in athletes corresponded with the nature of the
      haemodynamic stimulus imposed on the ventricles during repeated exercise bouts.
      Endurance training purportedly leads to an eccentric form of cardiac hypertrophy,
      principally characterized by increased left ventricular (LV) cavity dimension,
      and thus LV mass (LVM), as a consequence of prolonged repetitive volume overload.
      In contrast, strength training is supposedly associated with a concentric form of
      hypertrophy where increased ventricular wall thickness, with no change in cavity
      size, underpins the elevated LVM as a consequence of the pressure overload
      produced during strenuous resistive exercise. The 'Morganroth hypothesis' has
      been broadly adopted in the scientific and medical literature, partly as a
      consequence of a large body of cross-sectional evidence suggesting that endurance
      athletes have greater cavity dimensions than control subjects or resistance
      athletes. However, in conflict with the 'Morganroth hypothesis', several studies
      suggest that LV wall thickness is increased more in endurance-, than strength
      trained athletes and others have reported no morphological changes in resistance
      trained athletes. Such controversial data may reflect variability in the training
      stimuli, with little obvious attempt to quantify these issues in previous
      research. Further reflection on the 'Morganroth hypothesis' may also be pertinent
      as more sensitive technologies, such as magnetic resonance imaging, are now being
      employed for the assessment of cardiac morphology. Finally, the process of
      scaling (or normalizing) cardiac size for between-subject differences in body
      size and composition has further complicated the description and understanding of
      cardiac morphology in athletes. Specifically, it is possible that the increased
      LVM observed in some athletes may merely reflect a 'larger than normal' body
      size. These considerations emphasise the limitations of the predominance of cross
      sectional comparisons in the available literature, which assume that differences
      between groups are due to a training effect per se rather than other between
      subject differences. The small number of longitudinal training studies undertaken
      in athletes suggest that individuals with athlete's heart can exhibit further
      cardiac adaptation in response to training resumption. Longitudinal training
      studies undertaken in previously sedentary subjects generally indicate that
      exercise results in enlargement of LV cavity size, increases in wall thickness or
      LVM following training. However, there are currently limited longitudinal data
      available to comment on the effects of different modalities of exercise training
      on LV cavity dimension and wall thickness. In summary, significant caveats
      related to cross-sectional literature, the relative insensitivity of
      echocardiographic measurements and the paucity of evidence from longitudinal
      exercise training studies, warrant ongoing research to verify the 'Morganroth
      hypothesis'.

PMID- 18081369
TI  - Aromatase inhibitors in early hormone receptor-positive breast cancer : what is
      the optimal initiation time for the maximum benefit?
AB  - Breast cancer is common, affecting one in nine women worldwide. As stipulated by
      the St Gallen consensus guidelines, hormone therapy is an integral part of
      treatment for hormone-responsive disease. Previously, this has been with
      tamoxifen; however, as a result of a number of recent studies, aromatase
      inhibitors are now competing for use as first-line agents. In addition, there is
      as yet no firm consensus as to when and how these drugs should be used within the
      adjuvant setting. This article reviews the use of aromatase inhibitors in early
      stage hormone-positive breast cancer. It describes the evidence from the studies
      involving the aromatase inhibitors in an upfront, switch and extended setting. It
      further discusses the mathematical models proposed to determine the optimum
      timing of initiation. In light of the ongoing research into predictive
      biomarkers, this review then concentrates on whether future focus should be on
      more individualized treatment strategies than the optimum timing of aromatase
      inhibitors.

PMID- 18081370
TI  - Antiepileptic drug development in children: considerations for a revisited
      strategy.
AB  - The European Commission and the European Parliament have acknowledged the
      specific need for a proper evaluation of new drugs in children. The evaluation of
      the antiepileptic drugs (AEDs) available on the market illustrates the deficit in
      therapeutic trials for childhood epilepsy syndromes. Currently, the development
      of AEDs is mainly performed in children with focal epilepsy, whereas infants and
      the specific age-related epilepsy syndromes, particularly epileptic
      encephalopathies, are neglected. Infantile epilepsies remain 'therapeutic
      orphans', although they are the most frequent and deleterious disorders in the
      area of epilepsy. In order to circumvent the difficulties faced when conducting
      AED trials in children, we addressed the question of improving feasibility
      without decreasing quality, while optimally taking into account paediatric
      ethical requirements. For this review, we first raise the issues of paediatric
      epilepsies that require special considerations for randomized controlled trials
      (RCTs) in children. Then, we attempt to determine to what extent adult data could
      be extrapolated to children. Finally, we review innovative approaches that could
      be used in the evaluation of AEDs in children. The main specificities of
      paediatric epilepsies (heterogeneity, severity, cognitive impact,
      pharmacoresistance, syndrome-specific efficacy profile) are related to brain
      development and should be taken into consideration when establishing specific
      guidelines for the evaluation of AEDs in children. Extrapolating efficacy data
      from adults to children may be possible in focal epilepsy except in infants who
      need age-specific trials. Epileptic encephalopathies do not exist in adults and
      require specific trials. Pharmacokinetic data are required below a lower age
      limit for extrapolation of adult data to be determined in a case-to-case
      approach. Safety data are required at any paediatric age. RCTs in small but
      homogeneous populations in each paediatric-specific epileptic syndrome, the use
      of sequential or responder-enrichment designs, and population pharmacokinetics
      represent potentially promising approaches to evaluate drugs in children in an
      efficient way.

PMID- 18081371
TI  - Nonresponse to treatment for hepatitis C: current management strategies.
AB  - Chronic hepatitis C affects >170 million people worldwide, causing cirrhosis and
      liver cancer in a sizeable proportion of patients. Substantial progress has been
      made in the treatment of chronic hepatitis C. More than 50% of patients can
      achieve sustained virological response after 24-48 weeks of interferon and
      ribavirin combination therapy, making chronic hepatitis C a potentially curable
      disease. However, a large proportion of patients with chronic hepatitis C do not
      clear the virus after current standard therapy. Hepatitis C virus develops two
      pathways to counteract the antiviral effect of interferon. Some chronic hepatitis
      C patients may have a virus that is more resistant to interferon therapy, while
      other patients appear to have defective immune responses or poor tolerance or
      compliance to interferon-based antiviral therapy. The possible strategies to
      improve antiviral efficiency in these nonresponders are to increase the dosage,
      prolong the duration of treatment and improve the compliance of patients. A total
      of 6-15% of prior nonresponders to standard interferon plus ribavirin therapy
      will respond to re-treatment with peginterferon plus ribavirin, while 32-50% of
      patients who have relapsed will respond to re-treatment. New small molecules are
      under development to treat chronic hepatitis C and may be important particularly
      in the treatment of prior nonresponders to current standard therapy.

PMID- 18081373
TI  - Pharmacological treatment of early multiple sclerosis.
AB  - Currently, six medications are approved by the US FDA for the treatment of
      relapsing forms of multiple sclerosis (MS). In contrast, no pharmacological agent
      has proved to be effective in patients with secondary-progressive MS without
      relapses, or in patients with primary-progressive MS. One of the principal issues
      concerning an optimal pharmacotherapy for relapsing forms of MS is the optimal
      time of treatment initiation. There is now an almost universal consensus among MS
      experts that many patients will benefit from early therapy. However, several
      formidable challenges exist in identifying individuals who will benefit versus
      those who will do well without intervention. How do we define early MS and what
      clinical and paraclinical markers may be useful in defining the timing and nature
      of therapy? Do patients with a benign form of MS require therapy or are they
      exposed unnecessarily to adverse effects of our currently available medications?
      How do we identify disease progression and treatment failures? This review
      discusses these issues and outlines the evidence for application of 'early'
      treatment in patients with relapsing forms of MS.

PMID- 18081372
TI  - Antiretroviral therapy : optimal sequencing of therapy to avoid resistance.
AB  - In the second decade of highly active antiretroviral therapy, drug regimens offer
      more potent, less toxic and more durable choices. However, strategies addressing
      convenient sequential use of active antiretroviral combinations are rarely
      presented in the literature. Studies have seldom directly addressed this issue,
      despite it being a matter of daily use in clinical practice. This is, in part,
      because of the complexity of HIV-1 resistance information as well as the
      complexity of designing these types of studies. Nevertheless, several principles
      can effectively assist the planning of antiretroviral drug sequencing. The
      introduction of tenofovir disoproxil fumarate, abacavir and emtricitabine into
      current nucleoside backbone options, with each of them selecting for an
      individual pattern of resistance mutations, now permits sequencing in the context
      of previously popular thymidine analogues (zidovudine and stavudine). Similarly,
      newer ritonavir-boosted protease inhibitors could potentially be sequenced in a
      manner that uses the least cross-resistance prone protease inhibitor at the start
      of therapy, while leaving the most cross-resistance prone drugs for later, as
      long as there is rationale to employ such a compound because of its utility
      against commonly observed drug-resistant forms of HIV-1.

PMID- 18081374
TI  - Sevelamer hydrochloride: a review of its use for hyperphosphataemia in patients
      with end-stage renal disease on haemodialysis.
AB  - Sevelamer (Renagel), an orally administered metal-free cationic hydrogel
      polymer/resin that binds dietary phosphate in the gastrointestinal (GI) tract, is
      approved for use in the US, Europe and several other countries for the treatment
      of hyperphosphataemia in adult patients with end-stage renal disease (ESRD) on
      haemodialysis or peritoneal dialysis.Clinical evidence shows that sevelamer was
      at least as effective as calcium acetate and calcium carbonate at controlling
      serum phosphorus, calcium-phosphorus product (Ca x P) and intact parathyroid
      hormone (iPTH) levels, but generally reduced serum calcium levels to a greater
      extent and was associated with a lower risk of hypercalcaemic episodes than
      calcium-based phosphate binders. Sevelamer appeared to slow the progression of
      cardiovascular calcification in patients with ESRD and also had a beneficial
      effect on serum low-density lipoprotein-cholesterol (LDL-C) levels. In patients
      receiving chronic haemodialysis, there was no between-group difference in all
      cause mortality between sevelamer and calcium-based phosphate binder therapy in
      the primary efficacy analysis in the large (n >2100), 3-year DCOR trial; in the
      smaller (n = 109) nonblind RIND trial in patients new to dialysis, data suggest
      there is an overall survival benefit with sevelamer versus calcium-based
      phosphate binder treatment. The relative survival benefits and cost effectiveness
      of these phosphate binder therapies remains to be fully determined. Sevelamer
      treatment was generally as well tolerated as calcium acetate or calcium carbonate
      treatment. Overall, sevelamer is a valuable option for the management of
      hyperphosphataemia in patients with ESRD on haemodialysis.

PMID- 18081375
TI  - Parnaparin : a review of its use in the management of venous thromboembolism,
      chronic venous disease and other vascular disorders.
AB  - Parnaparin (Fluxum) is a low molecular weight heparin (LMWH) that is effective
      and generally well tolerated in the prevention of venous thrombosis, and in the
      treatment of chronic venous disease and venous and arterial thrombosis. Overall,
      the efficacy of parnaparin is at least as good as that of unfractionated heparin
      (UFH), but recent data indicate that parnaparin is more effective in preventing a
      triple composite endpoint of death, acute myocardial infarction (MI) and
      myocardial revascularisation in patients with unstable angina or acute ST-segment
      elevation myocardial infarction (STEMI). As with other LMWHs, parnaparin has a
      more convenient, once-daily, subcutaneous administration regimen and better local
      tolerability than UFH. Very little evidence comparing LMWHs is available but,
      because of similarities between these agents, very large studies would be needed
      to show significant differences. Meanwhile, data indicate that parnaparin is a
      useful option in the range of available LMWHs.

PMID- 18081376
TI  - Diclofenac sodium injection (Dyloject): in postoperative pain.
AB  - *A new formulation of the nonselective NSAID diclofenac sodium suitable for
      intravenous bolus injection has been developed using hydroxypropyl beta
      cyclodextrin as a solubility enhancer (HPbetaCD diclofenac). * HPbetaCD
      diclofenac intravenous bolus injection was shown to be bioequivalent to the
      existing parenteral formulation of diclofenac containing propylene glycol and
      benzyl alcohol as solubilizers (PG-BA diclofenac), which is relatively insoluble
      and requires slow intravenous infusion over 30 minutes. * Single-dose HPbetaCD
      diclofenac 3.75, 9.4, 18.75, 25, 37.5, 50 and 75 mg administered by intravenous
      bolus injection produced significantly greater responses than placebo for total
      pain relief (TOTPAR) over 6 hours or pain intensity at 4 hours in the treatment
      of moderate or severe postoperative dental pain in randomized, double-blind
      trials. HPbetaCD diclofenac 37.5 and 75 mg were similar in efficacy to
      intravenous bolus ketorolac 30 mg. * In a well controlled trial, single-dose
      HPbetaCD diclofenac 75 mg intravenous bolus injection was shown to be superior to
      PG-BA diclofenac 75 mg intravenous infusion with respect to TOTPAR over 4 hours,
      indicating faster onset of analgesia in the treatment of moderate or severe
      postoperative dental pain. Both HPbetaCD diclofenac and PG-BA diclofenac were
      superior to placebo. * HPbetaCD diclofenac was generally well tolerated during
      single-dose treatment of postoperative pain. The tolerability profile was similar
      to that of PG-BA diclofenac, but with a lower incidence of thrombophlebitis.

PMID- 18081378
TI  - Fluorescent resonant energy transfer: correlated fluctuations of donor and
      acceptor.
AB  - Mounting evidence suggests that in single-molecule fluorescent resonant energy
      transfer (FRET) measurements, correlation between fluctuations in donor and
      acceptor may be important. We present a general theory to describe this
      correlation and its effect on the FRET rate. The correlation arises from low
      energy excitations (e.g., acoustic phonons) of the molecule to which a donor
      acceptor pair is attached, and results in an effective interaction between local
      environments or baths associated with the donor and the acceptor. The correlation
      is found to reduce the transfer rate, in particular, at short donor-acceptor
      distances. The theory can quantitatively explain recent measurements of
      polyproline peptides.

PMID- 18081377
TI  - Raltegravir.
AB  - * Raltegravir, the first in a new class of orally administered HIV type-1 (HIV-1)
      integrase inhibitors, selectively inhibits the strand transfer activity of HIV-1
      and its integration into human DNA, a key stage in retroviral propagation,
      thereby limiting viral replication and the infection of new cells. * In two
      randomized, double-blind (with in-house blinding), placebo-controlled,
      multicentre, ongoing phase III trials, the proportion of patients achieving HIV-1
      RNA loads of <400 copies/mL (primary endpoint) was significantly greater in
      raltegravir plus optimized background therapy (OBT) recipients than in placebo
      plus OBT recipients (preliminary 24-week results). * The proportion of patients
      achieving viral loads of <50 copies/mL was significantly greater with raltegravir
      plus OBT than with placebo plus OBT in the two studies. * In addition, mean CD4+
      cell counts (secondary endpoint) were significantly increased from baseline in
      patients receiving raltegravir plus OBT relative to those receiving placebo plus
      OBT. * Raltegravir therapy was well tolerated overall. The incidence of mild to
      moderate adverse events was similar in the raltegravir and placebo arms of the
      two randomized trials.

PMID- 18081379
TI  - The radiative lifetime of metastable CO (a 3Pi, v=0).
AB  - We present a combined experimental and theoretical study on the radiative
      lifetime of CO in the a (3)Pi(1,2), v=0 state. CO molecules in a beam are
      prepared in selected rotational levels of this metastable state, Stark
      decelerated, and electrostatically trapped. From the phosphorescence decay in the
      trap, the radiative lifetime is measured to be 2.63+/-0.03 ms for the a (3)Pi(1),
      v=0, J=1 level. From the spin-orbit coupling between the a (3)Pi and the A (1)Pi
      states a 20% longer radiative lifetime of 3.16 ms is calculated for this level.
      It is concluded that coupling to other (1)Pi states contributes to the observed
      phosphorescence rate of metastable CO.

PMID- 18081380
TI  - The importance of middle-range Hartree-Fock-type exchange for hybrid density
      functionals.
AB  - Hybrid functionals are responsible for much of the utility of modern Kohn-Sham
      density functional theory. When rigorously applied to solid-state metallic and
      small band gap systems, however, the slow decay of their nonlocal Hartree-Fock
      type exchange makes hybrids computationally challenging and introduces unphysical
      effects. This can be remedied by using a range-separated hybrid which only keeps
      short-range nonlocal exchange, as in the functional of Heyd et al. [J. Chem.
      Phys. 118, 8207 (2003)]. On the other hand, many molecular properties require
      full long-range nonlocal exchange, which can also be included by means of a range
      separated hybrid such as the recently introduced LC-omegaPBE functional [O. A.
      Vydrov and G. E. Scuseria, J. Chem. Phys. 125, 234109 (2006)]. In this paper, we
      show that a three-range hybrid which mainly includes middle-range Hartree-Fock
      type exchange and neglects long- and short-range Hartree-Fock-type exchange
      yields excellent accuracy for thermochemistry, barrier heights, and band gaps,
      emphasizing that the middle-range part of the 1/r potential seems crucial to
      accurately model these properties.

PMID- 18081381
TI  - Laboratory detection of the elusive HSCO+ isomer.
AB  - The rotational spectrum of protonated carbonyl sulfide, HSCO(+), has now been
      detected in the centimeter-wave band in a molecular beam by Fourier transform
      microwave spectroscopy. Rotational and centrifugal distortion constants have been
      determined from transitions in the K(a)=0 ladder of the normal isotopic species,
      and DSCO(+) and H(34)SCO(+). HSCO(+) is systematically more abundant by a factor
      of three than HOCS(+), the isomer obtained by attaching the H(+) to the other end
      of the molecule, which ab initio calculations long predicted to be higher in
      energy by 4-5 kcalmol. Because HSCO(+) is comparable in polarity to HOCS(+) and
      is apparently more stable and because OCS is widely distributed in astronomical
      sources, HSCO(+) is a good candidate for detection with radio telescopes.

PMID- 18081382
TI  - A coherent nonlinear optical signal induced by electron correlations.
AB  - The correlated behavior of electrons determines the structure and optical
      properties of molecules, semiconductors, and other systems. Valuable information
      on these correlations is provided by measuring the response to femtosecond laser
      pulses, which probe the very short time period during which the excited particles
      remain correlated. The interpretation of four-wave-mixing techniques, commonly
      used to study the energy levels and dynamics of many-electron systems, is
      complicated by many competing effects and overlapping resonances. Here we propose
      a coherent optical technique, specifically designed to provide a background-free
      probe for electronic correlations in many-electron systems. The proposed signal
      pulse is generated only when the electrons are correlated, which gives rise to an
      extraordinary sensitivity. The peak pattern in two-dimensional plots, obtained by
      displaying the signal versus two frequencies conjugated to two pulse delays,
      provides a direct visualization and specific signatures of the many-electron wave
      functions.

PMID- 18081383
TI  - A simple and efficient CCSD(T)-F12 approximation.
AB  - A new explicitly correlated CCSD(T)-F12 approximation is presented and tested for
      23 molecules and 15 chemical reactions. The F12 correction strongly improves the
      basis set convergence of correlation and reaction energies. Errors of the Hartree
      Fock contributions are effectively removed by including MP2 single excitations
      into the auxiliary basis set. Using aug-cc-pVTZ basis sets the CCSD(T)-F12
      calculations are more accurate and two orders of magnitude faster than standard
      CCSD(T)/aug-cc-pV5Z calculations.

PMID- 18081384
TI  - Nuclear spin selection rules for reactive collision systems by the spin
      modification probability method.
AB  - The spin-modification probability (SMP) method, which provides fundamental and
      detailed quantitative information on the nuclear spin selection rules, is
      discussed more systematically and generalized for reactive collision systems
      involving more than one configuration of reactant and product molecules,
      explicitly taking account of the conservation of the overall nuclear spin
      symmetry as well as the conservation of the total nuclear spin angular momentum,
      under the assumption of no nuclear hyperfine interaction. The values of SMP once
      calculated can be used for any system of identical nuclei of any spin as long as
      the system has the corresponding nuclear spin symmetry. The values of SMP
      calculated for simple systems can also be used for more complex systems
      containing several kinds of identical nuclei or various isotopomers. The
      generalized formulation of statistical scattering theory which can easily
      represent various rearrangement mechanisms is also presented.

PMID- 18081385
TI  - A particle-particle, particle-density algorithm for the calculation of
      electrostatic interactions of particles with slablike geometry.
AB  - We present a fast and accurate method to calculate the electrostatic energy and
      forces of interacting particles with the boundary conditions appropriate to
      surfaces, i.e., periodic in the two directions parallel to the surface and free
      in the perpendicular direction. In the spirit of the Ewald method, the problem is
      divided into a short range and a long range part. The charge density responsible
      for the long range part is represented by plane waves in the periodic directions
      and by finite elements in the nonperiodic direction. Our method has computational
      complexity of O(N(g) log(N(g))) with a very small prefactor, where N(g) is the
      number of grid points.

PMID- 18081386
TI  - Split charge equilibration method with correct dissociation limits.
AB  - Analytic reactive potentials rely on electronegativity equalization to describe
      how the electron distribution is affected as chemical reactions occur. However,
      such models predict fractional charges for neutral species with different
      electronegativities. To overcome this well-known dissociation problem, an
      approach taking advantage of the concept of split charges [R. A. Nistor, J. G.
      Polihronov, M. H. Muser, and N. J. Mosey, J. Chem. Phys. 125, 094108 (2006)] is
      put forward. A first implementation is presented. Starting from a previous model
      [P. Bultinck, W. Langenaeker, P. Lahorte, F. D. Proft, P. Geerlings, M.
      Waroquier, and J. P. Tollenaere, J. Phys. Chem. A 106, 7887 (2002)], a new
      contribution to the total energy is introduced in order to make up for the lack
      of suitable constraints on the charge density. Its effect is to restrain charge
      transfer between remote atoms. As a consequence, systems in gas phase naturally
      decompose into neutral fragments. This result is achieved using two empirical
      parameters in addition to atomic electronegativities and hardnesses.

PMID- 18081387
TI  - Solving the Schrodinger equation for helium atom and its isoelectronic ions with
      the free iterative complement interaction (ICI) method.
AB  - The Schrodinger equation was solved very accurately for helium atom and its
      isoelectronic ions (Z=1-10) with the free iterative complement interaction (ICI)
      method followed by the variational principle. We obtained highly accurate wave
      functions and energies of helium atom and its isoelectronic ions. For helium, the
      calculated energy was 
      2.903,724,377,034,119,598,311,159,245,194,404,446,696,905,37 a.u., correct over
      40 digit accuracy, and for H(-), it was 
      0.527,751,016,544,377,196,590,814,566,747,511,383,045,02 a.u. These results prove
      numerically that with the free ICI method, we can calculate the solutions of the
      Schrodinger equation as accurately as one desires. We examined several types of
      scaling function g and initial function psi(0) of the free ICI method. The
      performance was good when logarithm functions were used in the initial function
      because the logarithm function is physically essential for three-particle
      collision area. The best performance was obtained when we introduce a new
      logarithm function containing not only r(1) and r(2) but also r(12) in the same
      logarithm function.

PMID- 18081388
TI  - The use of atomic intrinsic polarizabilities in the evaluation of the dispersion
      energy.
AB  - The recent approach presented by Becke and Johnson [J. Chem. Phys. 122, 154104
      (2005); 123, 024101 (2005); 123, 154101 (2005); 124, 174104 (2006); 124, 014104
      (2006)] for the evaluation of dispersion interactions based on the properties of
      the exchange-hole dipole moment is combined with a Hirshfeld-type partitioning
      for the molecular polarizabilities into atomic contributions, recently presented
      by some of the present authors [A. Krishtal et al., J. Chem. Phys. 125, 034312
      (2006)]. The results on a series of nine dimers, involving neon, methane, ethene,
      acetylene, benzene, and CO(2), taken at their equilibrium geometry, indicate that
      when the C(6), C(8), and C(10) terms are taken into account, the resulting
      dispersion energies can be obtained deviating 3% or 8% from high level literature
      data [E. R. Johnson and A. D. Becke, J. Chem. Phys. 124, 174104 (2006)], without
      the use of a damping function, the only outlier being the parallel face-to-face
      benzene dimer.

PMID- 18081389
TI  - Temperature, pressure, and isotope effects on the structure and properties of
      liquid water: a lattice approach.
AB  - We present a lattice model to describe the effect of isotopic replacement,
      temperature, and pressure changes on the formation of hydrogen bonds in liquid
      water. The approach builds upon a previously established generalized lattice
      theory for hydrogen bonded liquids [B. A. Veytsman, J. Phys. Chem. 94, 8499
      (1990)], accounts for the binding order of 1/2 in water-water association
      complexes, and introduces the pressure dependence of the degree of hydrogen
      bonding (that arises due to differences between the molar volumes of bonded and
      free water) by considering the number of effective binding sites to be a function
      of pressure. The predictions are validated using experimental data on the
      temperature and pressure dependence of the static dielectric constant of liquid
      water. The model is found to correctly reproduce the experimentally observed
      decrease of the dielectric constant with increasing temperature without any
      adjustable parameters and by assuming values for the enthalpy and entropy of
      hydrogen bond formation as they are determined from the respective experiments.
      The pressure dependence of the dielectric constant of water is quantitatively
      predicted up to pressures of 2 kbars and exhibits qualitative agreement at higher
      pressures. Furthermore, the model suggests a--temperature dependent--decrease of
      hydrogen bond formation at high pressures. The sensitive dependence of the
      structure of water on temperature and pressure that is described by the model
      rationalizes the different solubilization characteristics that have been observed
      in aqueous systems upon change of temperature and pressure conditions. The
      simplicity of the presented lattice model might render the approach attractive
      for designing optimized processing conditions in water-based solutions or the
      simulation of more complex multicomponent systems.

PMID- 18081390
TI  - Hyperfine resolved spectrum of the bromomethyl radical, CH2Br, by Fourier
      transform microwave spectroscopy.
AB  - Pure rotational spectra of the bromomethyl radical, CH(2)Br, were measured by
      using a Fourier transform microwave (FT-MW) spectrometer in order to fully
      resolve hyperfine structures arising from both the bromine and hydrogen nuclei.
      We detected a total of 124 lines for the (79)Br and (81)Br isotopomers, including
      K(a)=0 (ortho species) and K(a)=1 (para species). No hyperfine splitting due to
      the hydrogen nuclei was observed for the para species, directly confirming the
      planarity of the radical. We conducted a global analysis of our present FT-MW
      results and previous measurements in the millimeter-wave region and obtained an
      exhaustive list of molecular constants. The sign of the Fermi constant of the
      bromine nucleus was unambiguously determined to be positive, which is opposite to
      that found in previous work in the millimeter-wave region and in electron spin
      resonance experiment on this radical. The present study permitted a systematic
      comparison to be made of the hyperfine coupling constants of both the halogen and
      hydrogen nuclei for CH(2)X-type compounds, where X=F, Cl, and Br.

PMID- 18081391
TI  - The B 1Pi state of NaCs: high resolution laser induced fluorescence spectroscopy
      and potential construction.
AB  - The lowest (1)Pi state of the NaCs molecule, the B(1)(1)Pi state, was studied
      using a dye laser for inducing fluorescence that was resolved by a high
      resolution Fourier-transform spectrometer. The presence of argon buffer gas
      yielded rich rotational relaxation spectra allowing to enlarge the data set for
      the B(1)(1)Pi state, to obtain Lambda-splittings and to reveal numerous local
      perturbations. 543 weakly perturbed energy levels for rotational quantum numbers
      from J(')=5 to 168 and vibrational quantum numbers from v(')=0 to 25, which cover
      about 87% of the potential well depth, were used for a direct pointwise fit of
      the potential energy curve applying the inverted perturbation approach method.
      The resulting potential reproduces the term values for v(')=0-7 with an
      experimental accuracy of about 0.01-0.02 cm(-1), whereas for v(')=8-25 the
      deviations increase due to the perturbations, going to the order of 1 cm(-1); an
      extrapolation is made to the dissociation asymptote.

PMID- 18081392
TI  - Collisional quenching at ultralow energies: controlling efficiency with internal
      state selection.
AB  - Calculations have been carried out for the vibrational quenching of excited H(2)
      molecules which collide with Li(+) ions at ultralow energies. The dynamics has
      been treated exactly using the well-known quantum coupled-channel expansions over
      different initial vibrational levels. The overall interaction potential has been
      obtained from the calculations carried out earlier by our group using highly
      correlated ab initio methods. The results indicate that specific features of the
      scattering observables, e.g., the appearance of Ramsauer-Townsend minima in
      elastic channel cross sections and the marked increase of the cooling rates from
      specific initial states, can be linked to potential properties at vanishing
      energies (sign and size of scattering lengths) and to the presence of either
      virtual states or bound states. The suggestion is made such that by selecting the
      initial state preparation of the molecular partners, the ionic interactions would
      be amenable to controlling quenching efficiency at ultralow energies.

PMID- 18081393
TI  - Rydberg spectra of trans-1,2-dibromoethylene.
AB  - (2+1) resonance-enhanced multiphoton ionization spectra of jet-cooled trans-1,2
      dibromoethylene are reported for the first time. The two-photon spectral region
      between 149.7 and 141.2 nm was examined. A 4p(z)<--pi Rydberg transition between
      66,800 and 68,000 cm(-1) with A(g) excited state symmetry was analyzed, as well
      as two 4f<--pi Rydberg transitions with B(g) excited state symmetry and one 4f<-
      pi Rydberg transition with A(g) excited state symmetry between 68,000 and 70,800
      cm(-1). All Rydberg transitions observed in this work belong to series that
      converge to the first ionization potential of the molecule. The short vibrational
      progressions observed involve two totally symmetric in-plane normal modes: C=C-H
      bending (nu(3)) and C=C-Br bending (nu(5)) with average excited state frequencies
      of 829 and 226 cm(-1), respectively.

PMID- 18081394
TI  - The vibrationless A<--X transition of the jet-cooled deuterated methyl peroxy
      radical CD3O2 by cavity ringdown spectroscopy.
AB  - The nearly rotationally resolved spectrum of the A (2)A(')<--X (2)A(") 0(0)(0)
      transition of perdeutero methyl peroxy near 1.35 microm has been studied via
      pulsed cavity ringdown spectroscopy. Albeit, this is a weak transition, it is
      possible to observe the spectrum under jet-cooled conditions (approximately 15 K)
      by combining a source of narrow-bandwidth radiation (approximately 250 MHz) with
      a supersonic slit-jet expansion incorporating an electric discharge. The near
      infrared radiation was obtained by using stimulated Raman scattering and a
      pulsed, nearly Fourier-transform-limited Ti:sapphire amplifier seeded by a
      scanable cw Ti:sapphire ring laser. The experimental spectrum has been fitted
      using a model Hamiltonian that includes the rigid body rotation of an asymmetric
      top and the spin-rotation interaction. An excellent quality fit was obtained
      resulting in the determination of 15 molecular parameters characterizing the A
      and X states. Other results reported for CD(3)O(2) include an estimate of the
      radical concentration and the vibronic transition dipole from the observed
      absorption intensities. Details about the spectral linewidths are also discussed.

PMID- 18081395
TI  - High-resolution laser spectroscopy on the S1<--S0 transition of jet-cooled
      anthracene: rotational structure and Stark effect.
AB  - We present rotationally resolved spectra of the S(1)<--S(0) transition of
      anthracene at 27,687.153(4) cm(-1) as well as Stark effect measurements of the
      free anthracene molecule in electric fields of up to 85 kV/cm. The molecule is
      rotationally cooled in a supersonic jet expansion to a temperature of 4 K. The
      rotational constants of the electronic states S(0) and S(1) are determined by a
      simplex fit comparing the experimental spectra with simulations for an asymmetric
      rigid rotor. The measured and simulated energies are in very good agreement and
      the estimated accuracy of the rotational constants is 1 per thousand.
      Furthermore, the polarizabilities of the electronic states S(0) and S(1) are
      investigated. At an electric field of 85 kV/cm, line shifts of up to 150 MHz
      caused by a change in the polarizability of Deltaalpha=123(7) a.u. and
      broadenings due to the anisotropy are observed. The components of the tensor
      polarizabilities of the electronic states S(0) and S(1) are determined by
      simulating the complete spectra using second-order perturbation theory.

PMID- 18081396
TI  - Imaging studies of the photodissociation of H2S+ cations. I. Illustrations of the
      role of nuclear spin.
AB  - Ion imaging methods have been used to study the dynamics of H(2)(D(2)) molecular
      elimination from H(2)S(+)(D(2)S(+)) cations following photoexcitation to the
      A(2)A(1) state in the wavelength range 300<lambda<360 nm. Ground (X (2)B(1))
      state parent ions were formed by multiphoton ionization of a jet cooled
      H(2)S(D(2)S) sample, resonance enhanced at the two photon energy by the v=0 level
      of the (1)A(2)(... 2b(1) (1)4pb(2)(1)) Rydberg state. This Rydberg excited state
      predissociates sufficiently slowly that the 2+1 resonance enhanced multiphoton
      ionization (REMPI) spectrum shows resolved rovibronic structure, thereby allowing
      full quantum state selectivity at this intermediate stage of the cation
      preparation process. Analysis of the S(+) ion images following one photon
      excitation of the resulting H(2)S(+)(D(2)S(+)) cations shows that these fragments
      are formed in their ground (4)S state, and that the H(2)(D(2)) cofragments are
      formed predominantly (if not exclusively) in rotational states with either odd or
      even J rotational quantum number--depending on the chosen REMPI preparation
      wavelength. This striking specificity for forming ortho- or para-H(2)(D(2))
      products can be traced back to the state selectivity introduced in the REMPI
      preparation step. In the case of H(2)S, therefore, the nuclear spin symmetry of
      the two equivalent H nuclei in ortho-H(2)S (and H(2)S(+)) carries through into
      ortho-H(2) products, and para-H(2)S molecules map into para-H(2) fragments,
      surviving photoionization of the Rydberg state, photolysis of the resulting
      parent cation, and two subsequent radiationless transitions during the evolution
      from the photoexcited (A(2)A(1) state) cation through to S((4)S)+H(2) products.
      We identify two distinct fragmentation pathways. One, which we term route I,
      involves nonadiabatic (Renner-Teller) coupling to the X state at near linear
      configurations and subsequent (spin-orbit induced) coupling to the repulsive
      (4)A(2) potential energy surface (PES) at smaller bond angles. This process
      operates throughout the photolysis wavelength range investigated and yields
      rotationally "cool" and vibrationally "cold" H(2) products. The second (route II)
      shows a long wavelength threshold lambda approximately 335 nm, and gradually
      becomes dominant as the photolysis wavelength is reduced. Route II dissociation
      involves vibronically facilitated nonadiabatic transfer from the A to the
      B(2)B(2) state, followed by spin-orbit induced transfer to the (4)A(2) PES; the
      route II fragmentation dynamics results in H(2) products carrying higher levels
      of rotational and vibrational excitation.

PMID- 18081397
TI  - Imaging studies of the photodissociation of H2S+ cations. II.
AB  - Ion imaging methods have been used to explore the photodissociation dynamics of
      state-selected H(2)S(+) and D(2)S(+) cations. Predissociation following one
      photon excitation to the A (2)A(1) state at wavelengths (385< or =lambda(phot)<
      or =420 nm) in the vicinity of the first dissociation threshold results in
      formation of ground state S(+) fragment ions; the partner H(2)(D(2)) fragments
      are deduced to be rotationally "cold." Two photon dissociation processes are also
      observed, resonance enhanced at the energy of one absorbed photon by the
      predissociating A state levels. Two photon excitation at these wavelengths is
      deduced to populate an excited state of (2)A(1) symmetry, which dissociates to
      electronically excited S(+)((2)D) products, together with vibrationally excited
      H(2)(D(2)) cofragments. Ground state SH(+)(SD(+)) fragments, attributable to a
      one photon dissociation process, are observed once lambda(phot)< or =325 nm. Two
      photon induced production of SH(+)(SD(+)) fragments is also observed, at all
      wavelengths studied (i.e., at all lambda(phot)< or =420 nm). These SH(+)(SD(+))
      fragments are deduced to be formed in their singlet (i.e., a (1)Delta and b
      (1)Sigma(+)) excited states, with high levels of rotational excitation. The
      observed product branching and energy disposals are discussed within the context
      of the (limited) available knowledge relating to the excited electronic states of
      the H(2)S(+) cation.

PMID- 18081399
TI  - High-resolution slice imaging of quantum state-to-state photodissociation of
      methyl bromide.
AB  - The photodissociation of rotationally state-selected methyl bromide is studied in
      the wavelength region between 213 and 235 nm using slice imaging. A hexapole
      state selector is used to focus a single (JK=11) rotational quantum state of the
      parent molecule, and a high speed slice imaging detector measures directly the
      three-dimensional recoil distribution of the methyl fragment. Experiments were
      performed on both normal (CH(3)Br) and deuterated (CD(3)Br) parent molecules. The
      velocity distribution of the methyl fragment shows a rich structure, especially
      for the CD(3) photofragment, assigned to the formation of vibrationally excited
      methyl fragments in the nu(1) and nu(4) vibrational modes. The CH(3) fragment
      formed with ground state Br((2)P(3/2)) is observed to be rotationally more
      excited, by some 230-340 cm(-1), compared to the methyl fragment formed with spin
      orbit excited Br((2)P(1/2)). Branching ratios and angular distributions are
      obtained for various methyl product states and they are observed to vary with
      photodissociation energy. The nonadiabatic transition probability for the
      (3)Q(0+)-->(1)Q(1) transition is calculated from the images and differences
      between the isotopes are observed. Comparison with previous non-state-selected
      experiments indicates an enhanced nonadiabatic transition probability for state
      selected K=1 methyl bromide parent molecules. From the state-to-state
      photodissociation experiments the dissociationenergy for both isotopes was
      determined, D(0)(CH(3)Br)=23 400+/-133 cm(-1) and D(0)(CD(3)Br)=23 827+/-94 cm(
      1).

PMID- 18081398
TI  - Photoelectron spectroscopy of hydrated adenine anions.
AB  - We report the observation of hydrated adenine anions, A(-)(H(2)O)(n), n=1-7, and
      their study by anion photoelectron spectroscopy. Values for photoelectron
      threshold energies, E(T), and vertical detachment energies are tabulated for A(
      )(H(2)O)(n) along with those for hydrated uracil anions, U(-)(H(2)O)(n), which
      are presented for comparison. Analysis of these and previously measured
      photoelectron spectra of hydrated nucleobase anions leads to the conclusion that
      threshold energies significantly overstate electron affinity values in these
      cases, and that extrapolation of hydrated nucleobase anion threshold values to
      n=0 leads to incorrect electron affinity values for the nucleobases themselves.
      Sequential shifts between spectra, however, lead to the conclusion that A(
      )(H(2)O)(3) is likely to be the smallest adiabatically stable, hydrated adenine
      anion.

PMID- 18081400
TI  - Reference interaction site model and molecular dynamics study of structure and
      thermodynamics of methanol.
AB  - Thermodynamic and structural properties of various models of liquid methanol are
      investigated in the framework provided by the reference interaction site model
      (RISM) theory of molecular fluids. The theoretical predictions are systematically
      compared with molecular dynamics simulations both at ambient conditions and along
      a few supercritical isotherms. RISM results for the liquid-vapor phase separation
      are also obtained and assessed against available Gibbs ensemble Monte Carlo data.
      At ambient conditions, the theoretical correlations weakly depend on the specific
      details of the molecular models and reproduce the simulation results with
      different degrees of accuracy, depending on the pair of interaction sites
      considered. The position and the strength of the hydrogen bond are quite
      satisfactorily predicted. RISM results for the internal energy are almost
      quantitative whereas the pressure is generally overestimated. As for the liquid
      vapor phase coexistence, RISM predictions for the vapor branch and for the
      critical temperature are quite accurate; on the other side, the liquid branch
      densities, and consequently the critical density, are underestimated. We discuss
      our results in terms of intrinsic limitations, and suitable improvements, of the
      RISM approach in describing the physical properties of polar fluids, and in the
      perspective of a more general investigation of mixtures of methanol with nonpolar
      fluids of specific interest in the physics of associating fluids.

PMID- 18081401
TI  - Numerical calculation of the combinatorial entropy of partially ordered ice.
AB  - Using a one-parameter case as an example, we demonstrate that multicanonical
      simulations allow for accurate estimates of the residual combinatorial entropy of
      partially ordered ice. For the considered case, corrections to an (approximate)
      analytical formula are found to be small, never exceeding 0.5%. The method allows
      one as well to calculate combinatorial entropies for other systems.

PMID- 18081403
TI  - Global perspectives on the energy landscapes of liquids, supercooled liquids, and
      glassy systems: geodesic pathways through the potential energy landscape.
AB  - How useful it is to think about the potential energy landscape of a complex many
      body system depends in large measure on how direct the connection is to the
      system's dynamics. In this paper we show that, within what we call the potential
      energy-landscape ensemble, it is possible to make direct connections between the
      geometry of the landscape and the long-time dynamical behaviors of systems such
      as supercooled liquids. We show, in particular, that the onset of slow dynamics
      in such systems is governed directly by the lengths of their geodesics--the
      shortest paths through their landscapes within the special ensemble. The more
      convoluted and labyrinthine these geodesics are, the slower that dynamics is.
      Geodesics in the landscape ensemble have sufficiently well-defined
      characteristics that it is straightforward to search for them numerically, a
      point we illustrate by computing the geodesic lengths for an ordinary atomic
      liquid and a binary glass-forming atomic mixture. We find that the temperature
      dependence of the diffusion constants of these systems, including the precipitous
      drop as the glass-forming system approaches its empirical mode-coupling
      transition, is predicted quantitatively by the growth of the geodesic path
      lengths.

PMID- 18081402
TI  - Global perspectives on the energy landscapes of liquids, supercooled liquids, and
      glassy systems: the potential energy landscape ensemble.
AB  - In principle, all of the dynamical complexities of many-body systems are
      encapsulated in the potential energy landscapes on which the atoms move--an
      observation that suggests that the essentials of the dynamics ought to be
      determined by the geometry of those landscapes. But what are the principal
      geometric features that control the long-time dynamics? We suggest that the key
      lies not in the local minima and saddles of the landscape, but in a more global
      property of the surface: its accessible pathways. In order to make this notion
      more precise we introduce two ideas: (1) a switch to a new ensemble that
      deemphasizes the concept of potential barriers, and (2) a way of finding optimum
      pathways within this new ensemble. The potential energy landscape ensemble, which
      we describe in the current paper, regards the maximum accessible potential
      energy, rather than the temperature, as a control variable. We show here that
      while this approach is thermodynamically equivalent to the canonical ensemble, it
      not only sidesteps the idea of barriers it allows us to be quantitative about the
      connectivity of a landscape. We illustrate these ideas with calculations on a
      simple atomic liquid and on the Kob-Andersen [Phys. Rev. E 51, 4626 (1995)] of a
      glass-forming liquid, showing, in the process, that the landscape of the Kob
      Anderson model appears to have a connectivity transition at the landscape energy
      associated with its empirical mode-coupling transition. We turn to the problem of
      finding the most efficient pathways through potential energy landscapes in our
      companion paper.

PMID- 18081404
TI  - Solvent dependence of OH bend vibrational relaxation of monomeric water molecules
      in liquids.
AB  - The vibrational relaxation rates of the OH bending mode of monomeric H(2)O
      molecules diluted in various liquid halogenated methane and ethane derivates have
      been determined by a picosecond infrared pump-probe study. Relaxation time
      constants between 4.8 and 40.5 ps have been obtained. The discussion of the
      general solvent dependence suggests that in all cases the solvent fundamental
      with the smallest energy mismatch is favorably populated by this intermolecular
      energy transfer process.

PMID- 18081405
TI  - Nuclear spin dynamics using time-dependent projection operators: application to
      the saturation of dipolar order in slowly rotating samples.
AB  - An extension of the projection operators method is presented by considering
      explicit time-dependent projection operators. The usefulness of the present
      formalism is demonstrated by an investigation of nonadiabatic corrections to the
      evolution of a many-body system under a slow motion. A theoretical and
      experimental study of the saturation of nuclear spins dipolar order induced by a
      slow sample rotation is presented. Theoretically, the master equation of the
      dipolar order beyond the limit of an adiabatic evolution is established. It is
      shown how the time dependence of the projection operators is related to
      saturation of the dipolar order. A formal expression of the saturation rate is
      derived and its dependence upon the angle between rotation axis and external
      magnetic field is derived. Comparison with experimental data obtained on
      polycrystalline adamantane validates our theoretical approach.

PMID- 18081406
TI  - Liquid methanol Monte Carlo simulations with a refined potential which includes
      polarizability, nonadditivity, and intramolecular relaxation.
AB  - Monte Carlo simulations of liquid methanol were performed using a refined ab
      initio derived potential which includes polarizability, nonadditivity, and
      intramolecular relaxation. The results present good agreement between the
      energetic and structural properties predicted by the model and those predicted by
      ab initio calculations of methanol clusters and experimental values of gas and
      condensed phases. The molecular level picture of methanol shows the existence of
      both rings and linear polymers in the methanol liquid phase.

PMID- 18081407
TI  - Simple model for transport phenomena: microscopic construction of Maxwell
      demonlike engine.
AB  - We present a microscopic Hamiltonian framework to develop Maxwell demonlike
      engine. Our model consists of an equilibrium thermal bath and a nonequilibrium
      bath, latter generated by driving with an external stationary, Gaussian noise.
      The engine we develop can be considered as a device to extract work by modifying
      internal fluctuations. Our theoretical analysis focuses on finding the essential
      ingredients necessary for generating fluctuation induced transport under
      nonequilibrium condition. An important outcome of our model is that the net
      motion occurs when the nonlinear bath is modulated by the external noise,
      creating the nonzero effective temperature even when the temperature of both the
      baths are the same.

PMID- 18081408
TI  - Atomistic simulation of nanoporous layered double hydroxide materials and their
      properties. II. Adsorption and diffusion.
AB  - Nanoporous layered double hydroxide (LDH) materials have wide applications,
      ranging from being good adsorbents for gases (particularly CO(2)) and liquid ions
      to membranes and catalysts. They also have applications in medicine,
      environmental remediation, and electrochemistry. Their general chemical
      composition is [M(1-x)(II)M(x)(III)(OH(-))(2)](x+)[X(nm)(m-)nH(2)O], where M
      represents a metallic cation (of valence II or III), and X(nm)(m-) is an m
      valence inorganic, or heteropolyacid, or organic anion. We study diffusion and
      adsorption of CO(2) in a particular LDH with M(II)=Mg, M(III)=Al, and x
      approximately = 0.71, using an atomistic model developed based on energy
      minimization and molecular dynamics simulations, together with a modified form of
      the consistent-valence force field. The adsorption isotherms and self-diffusivity
      of CO(2) in the material are computed over a range of temperature, using
      molecular simulations. The computed diffusivities are within one order of
      magnitude of the measured ones at lower temperatures, while agreeing well with
      the data at high temperatures. The measured and computed adsorption isotherms
      agree at low loadings, but differ by about 25% at high loadings. Possible reasons
      for the differences between the computed properties and the experimental data are
      discussed, and a model for improving the accuracy of the computed properties is
      suggested. Also studied are the material's hydration and swelling properties. As
      water molecules are added to the pore space, the LDH material swells to some
      extent, with the hydration energy exhibiting interesting variations with the
      number of the water molecules added. The implications of the results are
      discussed.

PMID- 18081409
TI  - Methane dissociation on Ni(111): the effects of lattice motion and relaxation on
      reactivity.
AB  - The effects of lattice motion and relaxation on the dissociative adsorption of
      methane on a Ni(111) surface are explored. Electronic structure methods based on
      the density functional theory are used to compute the potential energy surface
      for this reaction. It is found that, in the transition state and product regions,
      there are forces causing the Ni atom over which the molecule dissociates to move
      out of the surface. In order to examine the extent to which the lattice might
      pucker during this reaction, high dimensional fully quantum scattering
      calculations are carried out. It is found that a significant amount of lattice
      puckering can occur, even at large collision energies, lowering the barrier to
      reaction and increasing the dissociative sticking probability. This is shown to
      be in contrast to the predictions of the surface oscillator model. While we
      observe similar puckering forces for this reaction on Pt(111), our calculations
      suggest that the puckering on this surface will be considerably less due to the
      larger metal atom mass. The "laser off" reactivities of CD(3)H on Ni(111) are
      computed, and it is demonstrated that there can be significant contributions to
      the reactivity from vibrationally excited molecules, particularly at lower
      collision energies, or when a large nozzle temperature is required to attain the
      necessary collision energy for reaction. Comparisons are made with recent
      experiments with regard to the variation of reactivity with collision energy,
      vibrational state, and surface temperature.

PMID- 18081410
TI  - Phase equilibria in model surfactants forming Langmuir monolayers.
AB  - The study of Langmuir monolayers has generated the attention of researchers
      because of their unique properties and their not well understood phase
      equilibrium. These monolayers exhibit interesting phase diagrams where the
      unusual liquid-liquid equilibrium can be observed for a single component
      monolayer. Monte Carlo computer simulations in the virtual Gibbs ensemble were
      used to obtain the phase diagram of Langmuir monolayers. The liquid-vapor and
      liquid-liquid phase equilibria were considered by constructing the Cailletet
      Mathias phase diagrams. By using the Ising model and the rectilinear
      approximations the identification of the critical properties for both equilibria
      was determined. These critical parameters were calculated as a function of the
      strength of the interaction between the surfactant molecules and the aqueous
      subphase. As a result, we have identified the coexistence between a liquid
      expanded state (LES)-vapor and the liquid condensed state-LES, in agreement with
      experimental and theoretical evidence in the literature. We obtained a clear
      separation of phases and a strong dependence on the strength of the solvent used.
      Namely, as the interaction between the solvent and the head of the surfactant
      increases, the critical properties also increase. Equilibrium states were
      characterized by computing thermodynamic quantities as a function of temperature
      and solvent strength.

PMID- 18081411
TI  - On the relative stabilities of gold nanoparticles.
AB  - We calculate and compare the relative free energies of ideal/pristine gold
      nanoparticles for morphologies produced previously in vapor synthesis computer
      simulations. The results in conjunction with previous work provide a unique and
      direct quantitative comparison between ideal thermodynamics and kinetics in the
      synthesis of gold nanoparticles for an identical system. The ideal/pristine free
      energies suggest that the I(h) morphology was the most stable structure up to the
      147(I(h)) followed by the TO(h) for all the remaining nanoparticle sizes. A
      grouping of m-D(h) structures was identified in the size range N=146-318 with
      stabilities which were very close to the most stable I(h) and TO(h) structures.
      The free energy analysis was somewhat at odds with population statistics obtained
      from our kinetic growth simulations where the I(h) dominated and where very
      little presumably stable TO(h) nanoparticles were produced, implying that kinetic
      mechanisms are more influential than thermodynamic considerations. On the other
      hand other possible reasons for such discrepancies are discussed; one of these
      includes an interesting observation where the I(h) morphology was found to have a
      unique ability to incorporate exposed surface disorder such as adatoms into
      stable hexagonal surface structures through internal and surface structural
      rearrangements, leading to a possible enhancement in stabilities of I(h)-type
      morphologies.

PMID- 18081412
TI  - On the formation mechanism of the "pancake" decahedron gold nanoparticle.
AB  - We have studied the thermodynamic and kinetic growth mechanisms behind the
      formation of the "pancake" decahedron (D(h)) gold nanoparticle using computer
      simulation. Free energy calculations showed that the full pancake morphology is
      thermodynamically unstable across all the nanoparticle size ranges studied.
      However, from observations of growth simulations we discovered that a kinetic
      transport mechanism plays a significant contributing role in the formation
      process through a transfer of adatoms from the top and bottom (111) D(h) faces to
      the side (100) faces. More specifically we observed how diffusing adatoms on the
      (111) face are at times "pulled" off this face and into the (111)-(100) edge of
      the D(h), forcing a row of (100) side atoms into a (1x5) hexagonal
      reconstruction. Subsequently, this row of atoms was observed to buckle and then
      deconstruct forcing adatoms out onto the (100) side face completing the transfer.
      This transport mechanism is shown to be the main kinetic driving force behind the
      growth of the thermodynamically unstable pancake D(h) nanoparticle. The observed
      mechanism has implications for the nonequilibrium morphologies of nanoparticles
      involving a (100)-(111) surface boundary, especially for systems with surface
      reconstructions which increase the density of the surface.

PMID- 18081413
TI  - Site-dependent electron-stimulated reactions in water films on TiO2(110).
AB  - Electron-stimulated reactions in thin [<3 ML (monolayer)] water films adsorbed on
      TiO(2)(110) are investigated. Irradiation with 100 eV electrons results in
      electron-stimulated dissociation and electron-stimulated desorption (ESD) of
      adsorbed water molecules. The molecular water ESD yield increases linearly with
      water coverage theta for 0< or =theta< or =1 ML and 1<theta< or =2 ML. However,
      for theta>1 ML, the water ESD yield per additional water molecule adsorbed (i.e.,
      the slope of the ESD yield versus coverage) is 3.5 times larger than for theta<1
      ML. In contrast, the number of water molecules dissociated per incident electron
      increases linearly for theta< or =2 ML without changing slope at theta=1 ML. The
      total electron-stimulated sputtering rate, as measured by postirradiation
      temperature programmed desorption of the remaining water, is larger for theta>1
      ML due to the increased water ESD for those coverages. The water ESD yields
      versus electron energy (for 5-50 eV) are qualitatively similar for 1, 2, and 40
      ML water films. In each case, the observed ESD threshold is at approximately 10
      eV and the yield increases monotonically with increasing electron energy. The
      results indicate that excitations in the adsorbed water layer are primarily
      responsible for the ESD in thin water films on TiO(2)(110). Experiments on
      "isotopically layered" films with D(2)O adsorbed on the Ti(4+) sites (D(2)O(Ti))
      and H(2)O adsorbed on the bridging oxygen atoms (H(2)O(BBO)) demonstrate that
      increasing the water coverage above 1 ML rapidly suppresses the electron
      stimulated desorption of D(2)O(Ti) and D atoms, despite the fact that the total
      water ESD and atomic hydrogen ESD yields increase with increasing coverage. The
      coverage dependence of the electron-stimulated reactions is probably related to
      the different bonding geometries for H(2)O(Ti) and H(2)O(BBO) and its influence
      on the desorption probability of the reaction products.

PMID- 18081414
TI  - Multiscale modeling of materials based on force and charge density fidelity.
AB  - The approximate representation of a quantum solid as an equivalent composite
      semiclassical solid is considered for insulating materials. The composite is
      comprised of point ions moving on a potential energy surface. In the classical
      bulk domain this potential energy is represented by potentials constructed to
      give the same structure and elastic properties as the underlying quantum solid.
      In a small local quantum domain the potential is determined from a detailed
      quantum calculation of the electronic structure. The new features of this well
      studied problem are (1) a clearly stated theoretical context in which
      approximations leading to the model are introduced, (2) the representation of the
      classical domain by potentials focused on reproducing the specific quantum
      response being studied, (3) development of "pseudoatoms" for a realistic
      treatment of charge densities where bonds have been broken to define the
      environment of the quantum domain, and (4) inclusion of polarization effects on
      the quantum domain due to its distant bulk environment. This formal structure is
      illustrated in detail for a SiO(2) nanorod. More importantly, each component of
      the proposed modeling is tested quantitatively for this case, verifying its
      accuracy as a faithful multiscale model of the original quantum solid. To do so,
      the charge density of the entire nanorod is calculated quantum mechanically to
      provide the reference by which to judge the accuracy of the modeling. The
      construction of the classical potentials, the rod, the pseudoatoms, and the
      multipoles is discussed and tested in detail. It is then shown that the quantum
      rod, the rod constructed from the classical potentials, and the composite
      classical/quantum rod all have the same equilibrium structure and response to
      elastic strain. In more detail, the charge density and forces in the quantum
      subdomain are accurately reproduced by the proposed modeling of the environmental
      effects even for strains beyond the linear domain. The accuracy of the modeling
      is shown to apply for two quite different choices for the underlying quantum
      chemical method: transfer Hamiltonian and density functional methods.

PMID- 18081415
TI  - How cationic gold clusters respond to a single sulfur atom.
AB  - Results describing the interaction of a single sulfur atom with cationic gold
      clusters (Au(n) (+), n=1-8) using density functional theory are described.
      Stability of these clusters is studied through their binding energies, second
      order differences in the total energies, fragmentation behavior, and atom
      attachment energies. The lowest energy structures for these clusters appear to be
      three dimensional right from n=3. In most cases the sulfur atom in the structure
      of Au(n)S(+) is observed to displace the gold atom siting at the peripheral site
      of the Au(n) (+) cluster. The dissociation channels of Au(n)S(+) clusters follow
      the same trend as Au(n) (+) cluster, based on the even/odd number of gold atoms
      in the cluster, with the exception of Au(3)S(+). This cluster dissociates into Au
      and Au(2)S(+), signifying the relative stability of Au(2)S(+) cluster regardless
      of having an odd number of valence electrons. Clusters with an even number of
      gold atoms dissociate into Au and Au(n-1)(S)(+) and clusters with an odd number
      of gold atoms dissociate into Au(2) and Au(n-2)(S)(+) clusters. An empirical
      relation is found between the conduction molecular orbital and the number of
      atoms in the Au(n)S(+) cluster.

PMID- 18081416
TI  - Study on the interaction between tetracene and Cu(110) surface.
AB  - The electronic structure of tetracene on Cu (110) surface has been studied by
      using ultraviolet photoemission spectroscopy (UPS). The emission features from
      the organic molecule are located from 1 to 10 eV below the Fermi level, and they
      shift in binding energy with increasing the coverage of the organic material. For
      the surface with multilayer of tetracene, six well-resolved features were found
      at 1.90, 3.40, 4.70, 5.95, 6.95, and 9.15 eV below the Fermi level, respectively.
      On the surface with a lower coverage of tetracene, angle-resolved UPS
      measurements suggest that the molecular plane is parallel to the substrate.
      Density functional theory calculation confirms the flat-lying adsorption mode and
      shows that the tetracene molecule prefers to be adsorbed on the long bridge site
      with its long axis in the [110] azimuth.

PMID- 18081417
TI  - Structure, energetics, and bonding of amorphous Au-Si alloys.
AB  - First principles periodic calculations based on gradient-corrected density
      functional theory have been performed to examine the structure, energetics, and
      bonding of amorphous Au-Si alloys with varying Au:Si composition ratios. Our
      results predict that the Au-Si alloy forms the most stable structure when the Si
      content is around 40-50 at. %, with an energy gain of about 0.15 eV/atom. In
      addition, the volume change per atom in the alloy exhibits a distinctive
      nonlinear trend, with the minimum value around 60 at. % Si. The occurrence of the
      minimum in the Au-Si mixing energy and volume is attributed to strong
      hybridization of the Au 5d-Si 3p states. We also present variations in the radial
      distribution function and atomic coordination number as a function of Au:Si
      composition ratio, with discussion of the nature of local packing and chemical
      bonding in the Au-Si alloy system.

PMID- 18081418
TI  - Molecular dynamics simulation of nanocolloidal amorphous silica particles: Part
      I.
AB  - Explicit molecular dynamics simulations were applied to a pair of amorphous
      silica nanoparticles in aqueous solution, with diameter of 4.4 nm and with four
      different background electrolyte concentrations, to extract the mean force acting
      between the two silica nanoparticles. Dependences of the interparticle forces on
      the separation and the background electrolyte concentration were demonstrated.
      The nature of the interaction of the counterions with charged silica surface
      sites (deprotonated silanols) was investigated. A "patchy" double layer of
      adsorbed sodium counterions was observed. Dependences of the interparticle
      potential of mean force on the separation and the background electrolyte
      concentration were demonstrated. Direct evidence of the solvation forces is
      presented in terms of changes of the water ordering at the surfaces of the
      isolated and double nanoparticles. The nature of the interaction of the
      counterions with charged silica surface sites (deprotonated silanols) was
      investigated in terms of quantifying the effects of the number of water molecules
      separately inside each pair of nanoparticles by defining an impermeability
      measure. A direct correlation was found between the impermeability (related to
      the silica surface "hairiness") and the disruption of water ordering. Differences
      in the impermeability between the two nanoparticles are attributed to differences
      in the calculated electric dipole moment.

PMID- 18081419
TI  - Transient diffusion in a tube with dead ends.
AB  - A particle diffusing in a tube with dead ends, from time to time enters a dead
      end, spends some time in the dead end, and then comes back to the tube. As a
      result, the particle spends in the tube only a part of the entire observation
      time that leads to slowdown of its diffusion along the tube. We study the
      transient diffusion in a tube with periodic identical dead ends formed by
      cavities of volume V(cav) connected to the tube by cylindrical channels of length
      L and radius a, which is assumed to be much smaller than the tube radius R and
      the distance l between neighboring dead ends. Assuming that the particle initial
      position is uniformly distributed over the tube, we analyze the monotonic
      decrease of the particle diffusion coefficient D(t) from its initial value
      D(0)=D, which characterizes diffusion in the tube without dead ends, to its
      asymptotic long-time value D(infinity)=D(eff)<D. We derive an expression for the
      Laplace transform of D(t), denoted by D(s), where s is the Laplace parameter.
      Although the expression is too complicated to be inverted analytically, we use it
      to find the relaxation time of the process as a function of the geometric
      parameters of the system mentioned above. To check the accuracy of our results,
      we ran Brownian dynamics simulations and found the mean squared displacement of
      the particle as a function of time by averaging over 5x10(4) realizations of the
      particle trajectory. The time-dependent mean squared displacement found in
      simulations is compared with that obtained by numerically inverting the Laplace
      transform of the mean squared displacement predicted by the theory, which is
      given by 2D(s)/s. Comparison shows excellent agreement between the two time
      dependences that support the approximations used when developing the theory.

PMID- 18081420
TI  - Lattice model of equilibrium polymerization. VI. Measures of fluid "complexity"
      and search for generalized corresponding states.
AB  - Particle association in "complex" fluids containing charged, polar, or polymeric
      molecular species often leads to deviations from the corresponding state
      description of "simple" fluids in which the molecules are assumed to have
      relatively symmetric interactions and shapes. This fundamental problem is
      addressed by developing a minimal thermodynamic model of activated equilibrium
      polymerization solutions that incorporates effects associated with the
      competition between van der Waals and associative interactions, as well as
      features related to molecular anisotropy and many-body interactions. As a dual
      purpose, we focus on thermodynamic signatures that can be used to identify the
      nature of dynamic clustering transitions and the interaction parameters
      associated with these rounded thermodynamic transitions. The analysis begins by
      examining "singular" features in the concentration dependence of the osmotic
      pressure Pi that generically characterize the onset of particle association.
      Because molecular self-assembly can strongly couple with fluid phase separation,
      evidence is also sought for associative interactions in the behavior of the
      second A(2) and third A(3) osmotic virial coefficients. In particular, the
      temperatures T(Theta2) and T(Theta3) where A(2) and A(3), respectively, vanish
      are found to contain valuable information about the relative strength of the
      associative and van der Waals interactions. The critical temperature T(c) for
      phase separation, the critical composition phi(c), and the rectilinear diameter
      A(d), describing the asymmetry of the coexistence curve for phase separation,
      along with the average cluster mass L(c) and extent of polymerization Phi(c) at
      the critical point, further specify the relevant interaction parameters of our
      model. Collectively, these characteristic properties provide a thermodynamic
      metric for defining fluid complexity and in developing a theoretically based
      corresponding state relation for complex fluids.

PMID- 18081421
TI  - Electric field-induced translocation of single-stranded DNA through a polarized
      carbon nanotube membrane.
AB  - Molecular dynamics simulations based on a novel polarizable nanotube model were
      performed to study the dynamics in translocation of a single-stranded
      deoxyribonucleic acid oligonucleotide through a polarized carbon nanotube
      membrane by an applied electric field. The study revealed a nonlinear dependence
      of translocation velocity and an inverse quadratic dependence of translocation
      time on the electric field strength, as well as a threshold electric field below
      which the translocation process becomes impossible. The translocation rate was
      found to be pore-size dependent. The polarizable nanotube model developed for
      this study provides a useful platform for investigating the dynamics of a range
      of bionanosystems.

PMID- 18081422
TI  - Quantum reaction rates and sampling of quantum equilibrium structure.

PMID- 18081423
TI  - Lessons from "lower" organisms: what worms, flies, and zebrafish can teach us
      about human energy metabolism.
AB  - A pandemic of metabolic diseases (atherosclerosis, diabetes mellitus, and
      obesity), unleashed by multiple social and economic factors beyond the control of
      most individuals, threatens to diminish human life span for the first time in the
      modern era. Given the redundancy and inherent complexity of processes regulating
      the uptake, transport, catabolism, and synthesis of nutrients, magic bullets to
      target these diseases will be hard to find. Recent studies using the worm
      Caenorhabditis elegans, the fly Drosophila melanogaster, and the zebrafish Danio
      rerio indicate that these "lower" metazoans possess unique attributes that should
      help in identifying, investigating, and even validating new pharmaceutical
      targets for these diseases. We summarize findings in these organisms that shed
      light on highly conserved pathways of energy homeostasis.

PMID- 18081424
TI  - AGEMAP: a gene expression database for aging in mice.
AB  - We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project) gene
      expression database, which is a resource that catalogs changes in gene expression
      as a function of age in mice. The AGEMAP database includes expression changes for
      8,932 genes in 16 tissues as a function of age. We found great heterogeneity in
      the amount of transcriptional changes with age in different tissues. Some tissues
      displayed large transcriptional differences in old mice, suggesting that these
      tissues may contribute strongly to organismal decline. Other tissues showed few
      or no changes in expression with age, indicating strong levels of homeostasis
      throughout life. Based on the pattern of age-related transcriptional changes, we
      found that tissues could be classified into one of three aging processes: (1) a
      pattern common to neural tissues, (2) a pattern for vascular tissues, and (3) a
      pattern for steroid-responsive tissues. We observed that different tissues age in
      a coordinated fashion in individual mice, such that certain mice exhibit rapid
      aging, whereas others exhibit slow aging for multiple tissues. Finally, we
      compared the transcriptional profiles for aging in mice to those from humans,
      flies, and worms. We found that genes involved in the electron transport chain
      show common age regulation in all four species, indicating that these genes may
      be exceptionally good markers of aging. However, we saw no overall correlation of
      age regulation between mice and humans, suggesting that aging processes in mice
      and humans may be fundamentally different.

PMID- 18081425
TI  - Genome organization and gene expression shape the transposable element
      distribution in the Drosophila melanogaster euchromatin.
AB  - The distribution of transposable elements (TEs) in a genome reflects a balance
      between insertion rate and selection against new insertions. Understanding the
      distribution of TEs therefore provides insights into the forces shaping the
      organization of genomes. Past research has shown that TEs tend to accumulate in
      genomic regions with low gene density and low recombination rate. However, little
      is known about the factors modulating insertion rates across the genome and their
      evolutionary significance. One candidate factor is gene expression, which has
      been suggested to increase local insertion rate by rendering DNA more accessible.
      We test this hypothesis by comparing the TE density around germline- and soma
      expressed genes in the euchromatin of Drosophila melanogaster. Because only
      insertions that occur in the germline are transmitted to the next generation, we
      predicted a higher density of TEs around germline-expressed genes than soma
      expressed genes. We show that the rate of TE insertions is greater near germline-
      than soma-expressed genes. However, this effect is partly offset by stronger
      selection for genome compactness (against excess noncoding DNA) on germline
      expressed genes. We also demonstrate that the local genome organization in
      clusters of coexpressed genes plays a fundamental role in the genomic
      distribution of TEs. Our analysis shows that-in addition to recombination rate
      the distribution of TEs is shaped by the interaction of gene expression and
      genome organization. The important role of selection for compactness sheds a new
      light on the role of TEs in genome evolution. Instead of making genomes grow
      passively, TEs are controlled by the forces shaping genome compactness, most
      likely linked to the efficiency of gene expression or its complexity and possibly
      their interaction with mechanisms of TE silencing.

PMID- 18081426
TI  - Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding
      yeast mitosis.
AB  - During cell division all chromosomes must be segregated accurately to each
      daughter cell. Errors in this process give rise to aneuploidy, which leads to
      birth defects and is implicated in cancer progression. The spindle checkpoint is
      a surveillance mechanism that ensures high fidelity of chromosome segregation by
      inhibiting anaphase until all kinetochores have established bipolar attachments
      to spindle microtubules. Bub1 kinase is a core component of the spindle
      checkpoint, and cells lacking Bub1 fail to arrest in response to microtubule
      drugs and precociously segregate their DNA. The mitotic role(s) of Bub1 kinase
      activity remain elusive, and it is controversial whether this C-terminal domain
      of Bub1p is required for spindle checkpoint arrest. Here we make a detailed
      analysis of budding yeast cells lacking the kinase domain (bub1DeltaK). We show
      that despite being able to arrest in response to microtubule depolymerisation and
      kinetochore-microtubule attachment defects, bub1DeltaK cells are sensitive to
      microtubule drugs. This is because bub1DeltaK cells display significant
      chromosome mis-segregation upon release from nocodazole arrest. bub1DeltaK cells
      mislocalise Sgo1p, and we demonstrate that both the Bub1 kinase domain and Sgo1p
      are required for accurate chromosome biorientation after nocodazole treatment. We
      propose that Bub1 kinase and Sgo1p act together to ensure efficient biorientation
      of sister chromatids during mitosis.

PMID- 18081430
TI  - Periadventitial adipose tissue (tunica adiposa): enemy or friend around?

PMID- 18081427
TI  - Rrp1b, a new candidate susceptibility gene for breast cancer progression and
      metastasis.
AB  - A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B
      (Rrp1b), was identified through two independent approaches. First, yeast two
      hybrid, immunoprecipitation, and functional assays demonstrated a physical and
      functional interaction between Rrp1b and the previous identified metastasis
      modifier Sipa1. In parallel, using mouse and human metastasis gene expression
      data it was observed that extracellular matrix (ECM) genes are common components
      of metastasis predictive signatures, suggesting that ECM genes are either
      important markers or causal factors in metastasis. To investigate the
      relationship between ECM genes and poor prognosis in breast cancer, expression
      quantitative trait locus analysis of polyoma middle-T transgene-induced mammary
      tumor was performed. ECM gene expression was found to be consistently associated
      with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM
      gene expression, tumor growth, and dissemination in metastasis assays.
      Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor
      cells predicted survival in a human breast cancer gene expression dataset.
      Finally, constitutional polymorphism within RRP1B was found to be significantly
      associated with tumor progression in two independent breast cancer cohorts. These
      data suggest that RRP1B may be a novel susceptibility gene for breast cancer
      progression and metastasis.

PMID- 18081432
TI  - Adequacy of pathology resident training for employment: a survey report from the
      Future of Pathology Task Group.

PMID- 18081428
TI  - Excess single-stranded DNA inhibits meiotic double-strand break repair.
AB  - During meiosis, self-inflicted DNA double-strand breaks (DSBs) are created by the
      protein Spo11 and repaired by homologous recombination leading to gene
      conversions and crossovers. Crossover formation is vital for the segregation of
      homologous chromosomes during the first meiotic division and requires the RecA
      orthologue, Dmc1. We analyzed repair during meiosis of site-specific DSBs created
      by another nuclease, VMA1-derived endonuclease (VDE), in cells lacking Dmc1
      strand-exchange protein. Turnover and resection of the VDE-DSBs was assessed in
      two different reporter cassettes that can repair using flanking direct repeat
      sequences, thereby obviating the need for a Dmc1-dependent DNA strand invasion
      step. Access of the single-strand binding complex replication protein A, which is
      normally used in all modes of DSB repair, was checked in chromatin
      immunoprecipitation experiments, using antibody against Rfa1. Repair of the VDE
      DSBs was severely inhibited in dmc1Delta cells, a defect that was associated with
      a reduction in the long tract resection required to initiate single-strand
      annealing between the flanking repeat sequences. Mutants that either reduce Spo11
      DSB formation or abolish resection at Spo11-DSBs rescued the repair block. We
      also found that a replication protein A component, Rfa1, does not accumulate to
      expected levels at unrepaired single-stranded DNA (ssDNA) in dmc1Delta cells. The
      requirement of Dmc1 for VDE-DSB repair using flanking repeats appears to be
      caused by the accumulation of large quantities of ssDNA that accumulate at Spo11
      DSBs when Dmc1 is absent. We propose that these resected DSBs sequester both
      resection machinery and ssDNA binding proteins, which in wild-type cells would
      normally be recycled as Spo11-DSBs repair. The implication is that repair
      proteins are in limited supply, and this could reflect an underlying mechanism
      for regulating DSB repair in wild-type cells, providing protection from
      potentially harmful effects of overabundant repair proteins.

PMID- 18081434
TI  - Critical values comparison: a College of American Pathologists Q-Probes survey of
      163 clinical laboratories.
AB  - CONTEXT: Critical laboratory values are values that may be indicative of life
      threatening conditions requiring rapid clinical intervention. Designation of
      critical values by clinical laboratories is required by the Clinical Laboratory
      Improvement Amendments and regulatory agencies. The development of critical
      values often involves consultation with clinical services. Also, questions are
      frequently asked about how critical values compare between institutions.
      OBJECTIVE: To examine and compare critical value ranges for selected common
      critical value analytes. Additional specific questions addressed the source of
      these values, the inclusion of specific items on a critical values list, and the
      procedures for establishing such lists. DESIGN: A total of 163 clinical
      laboratories provided critical values for potassium, calcium, magnesium, thyroid
      stimulating hormone, hemoglobin, platelet count, and activated partial
      thromboplastin time. Collected data were subjected to analysis for statistical
      variation. A questionnaire regarding demographic characteristics, institutional
      practices, and critical values management was also completed by participants.
      RESULTS: There was slight variation in pediatric and adult critical values used
      by the central 80% of study laboratories. Three areas of interest were noted: (1)
      27% of laboratories allowed nonpractitioners to accept inpatient critical value
      reports, (2) there was nonconsensus regarding the handling of outpatient critical
      values during weekday versus evening/weekend hours, and (3) only 56% of
      respondents had a written critical values policy or procedure. CONCLUSIONS:
      Pediatric and adult critical values for the selected analytes were consistent in
      a comparison between the 163 clinical laboratories. Several weaknesses in current
      critical values management were identified. A consensus critical values list that
      may be of value to other institutions was assembled.

PMID- 18081436
TI  - Vimentin reactivity in renal oncocytoma: immunohistochemical study of 234 cases.
AB  - CONTEXT: The expression of vimentin in benign renal oncocytomas has been
      controversial. However, this is of clinical significance because immunostains may
      be used in differential diagnosis of renal tumors on limited biopsy specimens.
      Using different staining and analysis methods, we studied vimentin
      immunoreactivity in a large series of renal oncocytomas with a special emphasis
      on the immunoreactivity patterns. OBJECTIVE: Immunohistochemical expression of
      vimentin has been used in the differential diagnosis of renal epithelial
      neoplasms. Although typically expressed in most renal cell carcinomas, the
      immunoreactivity of this intermediate filament in renal oncocytomas has been
      controversial. DESIGN: We studied vimentin immunoreactivity in a large series of
      234 renal oncocytomas using 2 staining methods as well as manual and automated
      imaging analyses. RESULTS: We found that the focal vimentin immunoreactivity can
      be seen in most (72.6%) renal oncocytomas with vimentin-positive tumor cells
      usually found in the edge of a central scar or in small clusters scattered
      throughout the tumor. Computer-aided imaging analysis using ChromaVision
      Automatic Cellular Imaging System II confirmed the difference in vimentin
      immunoreactivity between oncocytoma and other renal neoplasms. CONCLUSIONS: Our
      study of vimentin immunohistochemistry in a series of renal oncocytomas, which to
      our knowledge is the largest ever published, showed focal vimentin positivity
      detected in most oncocytomas. Because the vimentin staining patterns in renal
      oncocytomas are different from those seen in clear cell or papillary renal cell
      carcinomas, we consider vimentin staining to be helpful in the differential
      diagnosis of oncocytoma from other renal tumor mimics. Furthermore, strong
      vimentin positivity in a renal cell neoplasm does not exclude the diagnosis of
      renal oncocytoma, particularly in a limited biopsy specimen.

PMID- 18081435
TI  - A pilot study of vasculogenic mimicry immunohistochemical expression in
      hepatocellular carcinoma.
AB  - CONTEXT: The "de novo" formation of fluid-conducting patterns by tumor cells,
      termed vasculogenic mimicry (VM), is associated with increased mortality in many
      different solid tumors. OBJECTIVE: To identify VM patterns in hepatocellular
      carcinoma (HCC) and to determine whether these patterns were associated with more
      rapid tumor recurrence after orthotopic liver transplantation. DESIGN: Subjects
      included 20 patients who underwent orthotopic liver transplantation and were
      found to have HCC in the liver explant. Samples from 5 normal postmortem livers
      and 5 explanted livers with hepatitis C virus cirrhosis without HCC served as
      control tissues. Patterned matrix VM expression in HCC was identified by the
      presence of laminin-positive loops surrounding packets of tumor cells. Time to
      HCC recurrence after orthotopic liver transplantation was compared between
      patients with and without patterned VM expression. The relationships among VM in
      HCC, cause of chronic liver disease, serum alpha-fetoprotein level at the time of
      diagnosis, tissue expression by epidermal growth factor receptor, and endothelial
      markers including vascular endothelial growth factor and CD31 were assessed.
      RESULTS: Patterned matrix VM was identified in 11 of 20 primary HCC tissue
      samples. Vasculogenic mimicry was absent in all 10 control cases and was not
      identified in any area of dysplasia. The expression of VM in HCC lesions in liver
      explants was associated with more rapid posttransplant recurrence (P = .01).
      Vasculogenic mimicry was not associated with the cause of liver disease, serum
      alpha-fetoprotein level at time of diagnosis, or expression of epidermal growth
      factor receptor, vascular endothelial growth factor, or CD31. CONCLUSIONS:
      Vasculogenic mimicry of the patterned matrix type is present in hepatocellular
      carcinoma and is associated with tumor recurrence after orthotopic liver
      transplantation. Vasculogenic mimicry lesions are not associated with endothelial
      markers in HCC.

PMID- 18081437
TI  - Polymorphisms in TGFbeta and TNFalpha are associated with the myelodysplastic
      syndrome phenotype.
AB  - CONTEXT: Myelodysplastic syndromes (MDSs) are characterized by ineffective
      hematopoiesis, excessive apoptosis, and the aberrant expression of a number of
      cytokines. The genes encoding these cytokines are significantly polymorphic. It
      is unknown whether these cytokine polymorphisms are associated with, and may
      therefore be playing a role in the pathogenesis of, MDS. OBJECTIVE: To determine
      if certain polymorphisms in the tumor necrosis factor alpha (TNF-alpha) and
      transforming growth factor beta (TGF-beta) cytokines are overrepresented in a
      cohort of patients with MDSs. DESIGN: DNA was isolated from the peripheral blood
      or bone marrow aspirate of 21 patients with MDS. The genotypes for 4 different
      polymorphisms, 2 in TNFalpha and 2 in TGFbeta1, were determined using single
      specific-primer polymerase chain reaction. The allele and genotype frequencies
      were compared with similar populations in the National Cancer Institute SNP500
      database. RESULTS: In our MDS population, the -308A/A genotype of the TNFalpha
      gene and the TGFbeta1 allele +29T and genotype +29T/T, each associated with
      higher levels of expression, were overrepresented in our MDS population.
      CONCLUSIONS: Polymorphisms associated with increased expression in the cytokines
      TNFalpha and TGFbeta1 are overrepresented in the MDS population suggesting that
      increased TNF-alpha and TGF-beta1 activity may contribute to the susceptibility
      and/or pathogenesis of MDS. Further studies with larger sample sizes are
      warranted to confirm our observation.

PMID- 18081438
TI  - Patterns of add-on tests for hospitalized and for private patient populations.
AB  - CONTEXT: The policy of storing clinical samples in a pathology laboratory is
      based on long-standing practice rather than on objective data regarding the
      actual use of the stored samples. OBJECTIVE: To determine the time after initial
      order that requests for add-on tests are submitted to the laboratory. These data
      might be useful for improving the efficiency of sample storage. DESIGN: Two
      hundred sixteen add-on requests evenly divided between inpatients and private
      practice patients were reviewed for types of tests added on and the time of the
      requests. RESULTS: Ninety-five percent of add-on test requests for inpatients
      were made by 0.75 day after the initial order (range, 0.01-4.3 days). However,
      the 95th percentile for private practice patients' add-on requests did not occur
      until 5.6 days later (range, 0.01-7.0 days). The pattern of add-on tests for
      hospitalized patients also differed from those for private practice patients.
      Most add-on tests for hospitalized patients were for routine hospital tests, and
      the private practice add-on requests were for assays that were not as routine,
      frequently for testing referred to the reference laboratory. This difference
      affected the rapidity of completing the add-on tests. CONCLUSIONS: Samples for
      hospitalized patients can be stored for 3 days, but samples from patients in
      private practices should be held for 7 days. This change of "usual" storage
      practice would increase the efficient use of laboratory space and personnel.
      Screening all requests for add-on tests for hospitalized patients might reduce
      the frequency of unnecessary add-on requests, further increasing the efficiency
      of the laboratory.

PMID- 18081439
TI  - Novel criteria for parathyroid hormone levels in parathyroid hormone-guided
      parathyroid surgery.
AB  - CONTEXT: Novel criteria for decrease of perioperative parathyroid hormone
      measurement may improve the accuracy of perioperative quick parathyroid hormone
      (qPTH)-guided parathyroidectomy. OBJECTIVE: To assess overall cure rate based on
      conventional criteria (50% decline of qPTH). Perioperative qPTH levels were
      evaluated to determine novel criteria for successful parathyroid surgery. DESIGN:
      Analysis of perioperative qPTH measurement findings of all consecutive patients
      undergoing parathyroidectomy for hyperparathyroidism (72 with primary
      hyperparathyroidism and 28 with secondary or tertiary hyperparathyroidism or
      multiple endocrine neoplasia I/IIa disease). RESULTS: Measurement of qPTH (based
      solely on the criterion of greater than 50% decline of parathyroid hormone) in 72
      patients with primary hyperparathyroidism (77 procedures) showed true-positive
      results in 69, false-positive results in 4, and true-negative results in 4
      procedures. In our series, false-positive and true-negative results were
      associated with high postexcision levels. However, when qPTH declines of greater
      than 70% and 80% were used in cases of postexcision qPTH levels of 100 to 200
      ng/L and greater than 200 ng/L, respectively, no false-positive results were
      observed. CONCLUSIONS: Through adherence to these novel criteria, reexploration
      of the neck could have been prevented in 29% of patients with primary
      hyperparathyroidism due to multiple gland disease. These novel criteria demand
      future evaluation to establish their value.

PMID- 18081440
TI  - Tissue handling for genome-wide expression analysis: a review of the issues,
      evidence, and opportunities.
AB  - CONTEXT: Molecular diagnostic applications that use microarrays to analyze large
      numbers of genes simultaneously require high-quality mRNA. As these genome-wide
      expression assays become more commonly used in medical practice, pathologists and
      oncologists will benefit from understanding the importance of obtaining high
      quality RNA in order to generate reliable diagnostic and prognostic information,
      especially as these relate to cancer. OBJECTIVE: To review the effects that
      different tissue preservation techniques have on RNA quality and to provide
      practical advice on changes in tissue acquisition and handling that may soon be
      needed for certain clinical situations. DATA SOURCES: A review of recent
      literature on RNA quality, tissue fixation, cancer diagnosis, and gene expression
      analysis. CONCLUSIONS: Studies have consistently shown that frozen tissue yields
      more intact RNA than formalin-fixed, paraffin-embedded tissue. The chemical
      modification, cross-linking, and fragmentation caused by formalin fixation often
      render RNA unsuitable for microarray analysis. Thus, when expression analysis
      involving hundreds or more than 1000 gene markers is contemplated, pathologists
      should consider freezing a specimen within half an hour (preferably within
      minutes) of surgical resection and storing it at -80 degrees C or below. In
      coming years, pathologists will need to work closely with oncologists and other
      clinicians to determine when saving frozen tissue for microarray expression
      analysis is both practical and necessary. In select cases, the benefit of
      implementing a few extra tissue-handling steps may improve diagnostic and
      prognostic capability.

PMID- 18081441
TI  - Thrombotic microangiopathy in cocaine abuse-associated malignant hypertension:
      report of 2 cases with review of the literature.
AB  - Cocaine is one of the most commonly used illicit drugs. Acute renal failure is an
      emergent complication in patients with acute cocaine intoxication. It is well
      known that rhabdomyolysis and vasoconstriction can be important pathogenetic
      mechanisms resulting in acute renal failure in these patients. Clinically,
      although cocaine abuse is associated with elevated blood pressure, persistent
      accelerated hypertension reaching levels diagnostic of malignant hypertension is
      uncommon. Cocaine-induced malignant hypertension associated with morphologic
      features of thrombotic macroangiopathy has been rarely mentioned in the
      literature. We report 2 cases of cocaine abuse-associated malignant hypertension
      with renal failure. Kidney biopsies revealed thrombotic microangiopathy with
      fibrinoid necrosis of arterioles and glomerular tufts. Cocaine-mediated
      endothelial injury and platelet activation may play important pathogenetic roles
      in cocaine abusers who develop acute renal failure and malignant hypertension.

PMID- 18081442
TI  - Diffuse filiform polyposis with unique histology mimicking familial adenomatous
      polyposis in a patient without inflammatory bowel disease.
AB  - Filiform polyposis is an uncommon entity that is most often encountered in the
      colon of patients with a history of inflammatory bowel disease (IBD). Filiform
      polyposis is characterized by a large number of "wormlike" polyps lined by
      histologically normal colonic mucosa. These polyps can mimic adenomatous polyps.
      Only rare cases without a history or evidence of IBD have been reported.
      Neuromuscular and vascular hamartoma of the small bowel is a rare, focal disorder
      characterized by disorganized smooth muscle fascicles throughout the submucosa
      accompanied by fibrosis, nerve fibers, ganglion cells, and vessels. To our
      knowledge, there is only one report of this lesion in the large bowel (cecum),
      where it presented as a mass. Here we report the case of a 50-year-old man with
      no known history or symptoms of IBD presenting with filiform polyposis involving
      the entire colon, clinically mimicking familial adenomatous polyposis, and
      showing histologic features similar to neuromuscular and vascular hamartoma of
      the small bowel.

PMID- 18081443
TI  - Sclerosing epithelioid fibrosarcoma of the cecum: a radiation-associated tumor in
      a previously unreported site.
AB  - Data from the nuclear reactor explosion in Chernobyl and the atomic bomb
      detonations in Hiroshima and Nagasaki demonstrated an association between
      ionizing radiation and tumoriogenesis. There is a significant association between
      external beam radiation and radiation-induced sarcoma. Sclerosing epithelioid
      fibrosarcoma is a rare form of malignant fibrosarcoma that is low grade and
      indolent with distinct immunohistopathologic characteristics that usually occurs
      in the soft tissues of the extremities. A 62-year-old man from Kiev who aided in
      the cleanup at Chernobyl presented with crampy abdominal pain, nausea, and
      vomiting. His workup revealed a cecal mass, and the final pathology from his
      laparotomy confirmed sclerosing epithelioid fibrosarcoma with metastasis to the
      liver. In addition to a review of the literature, we report the first case of
      sclerosing epithelioid fibrosarcoma arising from the large bowel. Exposure to
      ionizing radiation from Chernobyl could have played a role in the development of
      his tumor.

PMID- 18081444
TI  - Amnion nodosum revisited: clinicopathologic and placental correlations.
AB  - Amnion nodosum is commonly regarded as a placental hallmark of severe and
      prolonged oligohydramnios. It consists of nodules of amorphous granular material
      present on the surface of the amnion. We reviewed all 45 cases of amnion nodosum
      from our placental database from 1994 through 2003 (study group). The control
      group consisted of 45 cases from the same database matched for gestational age
      but without amnion nodosum. Oligohydramnios, multiple pregnancy, perinatal
      mortality, macerated stillbirths, and chronic twin-twin transfusion were the most
      common clinical features encountered in the study group. Luminal vascular
      abnormalities of chorionic villi, fibrosis of chorionic villi, and placental
      edema were the placental features that were more frequently present in the study
      group.

PMID- 18081445
TI  - Bernard-Soulier syndrome: an inherited platelet disorder.
AB  - Bernard-Soulier syndrome is an inherited platelet disorder, which is transmitted
      in an autosomal recessive manner. This syndrome is characterized by variable
      thrombocytopenia and large defective platelets. Bernard-Soulier syndrome often
      presents early with bleeding symptoms, such as epistaxis, ecchymosis,
      menometrorrhagia, and gingival or gastrointestinal bleeding. Diagnosis can be
      confirmed by platelet aggregation studies and flow cytometry. The differential
      diagnosis includes the other inherited giant platelet disorders, as well as von
      Willebrand disease and immune thrombocytopenia purpura. Treatment is generally
      supportive with platelet transfusions when absolutely necessary and avoidance of
      antiplatelet medications. Recombinant activated factor VII and desmopressin have
      been used in attempts to shorten bleeding times; however, no definitive studies
      regarding their effectiveness have been reported.

PMID- 18081448
TI  - Snake bites in north east Sri Lanka.
AB  - INTRODUCTION: Snake bite is a major problem in Sri Lanka where recent decades of
      warfare and economic sanctions have complicated its management. RESULTS: A
      retrospective review of snake bites in north-east Sri Lanka was undertaken in
      2005 to review management. Of 303 victims, 145 revealed a local response, 134 a
      prolonged clotting time, 46 ptosis and five respiratory failure. One died. Of 97
      snakes identified: 42 were saw-scaled vipers, 14 Russell's vipers, 6 cobras and 6
      kraits. Most bites occurred at the harvest and the median age of victims was 32
      years. There was no difference in morbidity or mortality at any age. In total,
      262 snake bite cases were treated within 3 hours of the bite, and 183 were given
      antivenom. Seventy victims reacted adversely, of whom 61 received hydrocortisone,
      chlorpheniramine and subcutaneous adrenaline. No significant side effects were
      noted. CONCLUSION: North-east Sri Lanka has endured two decades of civil
      disruption but public knowledge and an established protocol for management,
      including adrenaline, has compensated for shortages in medical staff and
      infrastructure. The resumption of economic sanctions in 2007 is likely to counter
      that success.

PMID- 18081449
TI  - 'Perimeteritis' and rural health in Manitoba, Canada: perspectives from rural
      healthcare managers.
AB  - INTRODUCTION: Rural areas in many parts of the world are facing issues such as
      economic restructuring, environmental degradation, aging, and depopulation. These
      issues impact the health and wellbeing of the people living in rural communities.
      The purpose of this study was to assess rural healthcare managers' understanding
      of rural community wellbeing. Specifically, definitions were sought for rural,
      community, health, wellbeing, and healthy rural community. METHODS: The research
      reported in this article is based on a set of interviews with each of the 20
      healthcare professionals who either managed healthcare centres or administered
      specialized programs in the rural health care centres in the Assiniboine Regional
      Health Authority in southwestern Manitoba, Canada. RESULTS: Capitalizing on the
      open-ended structure of the interviews, respondents were thoughtful and
      philosophical in their responses. This produced a rich array of definitions of
      rural, community, health, wellbeing, and healthy rural community. In doing so,
      the struggles for rural communities in southwestern Manitoba were highlighted.
      The findings also illustrated that definitions of health and wellbeing do not fit
      standard biomedical or health determinant models alone. CONCLUSIONS: This study
      was a follow up to another study that employed focus groups to obtain rural
      resident perceptions of rural, community, wellbeing, and health in southwestern
      Manitoba. The study reported on here argued that the specific views of healthcare
      managers were necessary to further illustrate the complexities in understanding
      definitions of community and condition. The results are consistent with previous
      research on this topic in southern Manitoba and the recent literature in that
      there are no universally accepted definitions of rural, community, wellbeing, or
      health. Further, the study illustrated that professionals charged with managing
      healthcare services in rural Manitoba maintain very broad definitions of health
      and wellbeing. Most significantly, the determinants of health and wellbeing were
      central to defining individual and community condition and quality of life.

PMID- 18081450
TI  - Help wanted: newspapers seek Ph.D.'s in biomedical sciences.

PMID- 18081455
TI  - The eradication of poverty one child at a time through breastfeeding: a
      contribution to the global theme issue on poverty and human development, October
      22, 2007.

PMID- 18081456
TI  - The immune system in human milk and the developing infant.
AB  - The concept of the immune system in human milk emerged in the 1970s from clinical
      and laboratory observations made between the late 18th through the mid-20th
      centuries. The discovery of living leukocytes in human milk in 1970 was the final
      link to the chain of evidence that culminated in the concept. The concept was
      later expanded to include not only antimicrobial but also anti-inflammatory and
      immunoregulatory agents. These agents evolved to compensate for developmental
      delays in the immune system during infancy. Indeed, that explains the defense by
      human milk against common infectious diseases in infancy, necrotizing
      enterocolitis in preterm infants, and immune-mediated disorders such as Crohn's
      disease in later childhood. These diverse evolutionary outcomes underscore the
      superiority of human milk for the nutrition of human infants. Finally, other
      components of the immune system in human milk and their fate and functions in the
      developing infant may well be discovered in the near future.

PMID- 18081457
TI  - Effects of a human milk-derived human milk fortifier on the antibacterial actions
      of human milk.
AB  - OBJECTIVES: To compare the effects of a human breastmilk-derived fortifier on the
      antibacterial activity of milk obtained from lactating mothers delivering
      prematurely with the effects of a powdered fortifier on the same milk. STUDY
      DESIGN: Human milk samples were obtained after the first week of postnatal life
      from 10 lactating mothers, who had delivered prematurely. A bovine milk-based
      powdered fortifier and a human breastmilk-based frozen fortifier were evaluated.
      All mothers were healthy and they were not on any medications, although they were
      taking prenatal vitamins during lactation. The effects of each fortifier on the
      antimicrobial activity of milk toward Enterobacter sakazaki (ES), Escherichia
      coli, Clostridium difficile (CD), and Shigella soneii (SS) were evaluated by both
      the filter paper method and the growth inhibition method. RESULTS: Human milk
      inhibited the growth of all of the test organisms. This antibacterial activity
      was almost totally inhibited by the addition of the bovine protein-based human
      milk fortifier, while it remained unaffected by the addition of the human
      breastmilk-based fortifier. CONCLUSIONS: Breastmilk from women who have delivered
      preterm has antibacterial activity that can be affected by the addition of bovine
      based fortifier, but not by the addition of a human breastmilk-based fortifier.

PMID- 18081458
TI  - Microlipid-induced oxidative stress in human breastmilk: in vitro effects on
      intestinal epithelial cells.
AB  - OBJECTIVES: To (1) determine whether medium chain fatty acids (Microlipid) added
      to human breastmilk generates reactive oxygen species (ROS), and (2) measure the
      physiological effect(s) of Microlipid) (ML)-supplemented human breastmilk in an
      enterocyte cell culture bioassay. METHODS: ML was added to milk according to
      manufacturer's recommendations and total hydroperoxides measured at intervals
      with the FOX 2 and TBARS assays. Physiological effects of supplementation were
      measured using a human enterocyte cell line (Caco-2BBE) and/or a primary human
      fetal intestinal cell culture (FHS-74 Int). Endpoints included: intracellular
      oxidative stress, transepithelial electrical resistance (TEER), apoptosis, and
      interleukin (IL)-6 production. RESULTS: Immediately postsupplementation, ML did
      not significantly increase ROS, as determined by both the FOX 2 and TBARS assays.
      Further, storage of milk + ML at 4 degrees C prevented significant increases in
      total hydroperoxides. However, by 4 hours postsupplementation at room
      temperature, both assays revealed significantly higher hydroperoxide and lipid
      peroxide levels. ML-supplemented milk stored at room temperature for 4 hours had
      the following effects in cell culture bioassays: elevated oxidative stress,
      increased rates of apoptosis, decreased transmembrane electrical resistance
      (TEER) values and, in both cell culture assays, significantly increased secretion
      of IL-6. CONCLUSIONS: Based on our measurements of extracellular and
      intracellular ROS, milk supplemented with fresh ML does not induce significant
      oxidative stress. However, when stored for 4 hours at room temperature, ML
      induces significant levels of oxidative stress. Decreases in TEER and increases
      in apoptosis and IL-6 secretion are consistent with ML-induced oxidative stress.
      It therefore is likely that in clinical situations, if ML-supplemented milk is
      not administered quickly, the newborn may be placed at greater risk of oxidative
      stress.

PMID- 18081459
TI  - A breastfeeding e-learning project based on a web forum.
AB  - OBJECTIVE: The Internet has introduced new ways of learning that may complement
      medical training during the residency period. We describe the experience with a
      new method of e-learning for training in human lactation and breastfeeding
      counselling. Pediatric residents participated in the Human Lactation Forum
      maintained by the Spanish Pediatric Association Breastfeeding Committee, a site
      on the Internet where parents may write in for pediatric advice on breastfeeding.
      METHODS: From April 2005 to May 2006, 42 pediatric residents from four hospitals
      in Spain received a month of intensive theoretical training on breastfeeding, and
      afterward, they took weekly turns answering parents' questions in the forum.
      Before and after the experience, they completed a pre-post knowledge test and an
      opinion postexperience questionnaire with open questions. A t-test was used to
      analyze the differences pre- and posttest; the opinion questionnaire was analyzed
      qualitatively. RESULTS: The mean age of participants was 28.3 years; 88% were
      women, and 80% were in their third or fourth year of residency. The percentage of
      correct answers was higher after participation in the program, and the difference
      had statistic significance. The residents estimated that nearly a half of their
      patients needed breastfeeding advice, and they thought that the program improved
      their knowledge of breastfeeding and their communication skills with mothers. On
      average, they spent 2.9 hours daily to answer the questions. CONCLUSIONS: The
      learning experience was positively evaluated by the participants and contributed
      to increase their knowledge and skills in breastfeeding issues. We think it is a
      good method for training future pediatricians on breastfeeding management. In
      addition, the instrument may contribute to improve lactation knowledge among
      pediatricians.

PMID- 18081460
TI  - A critical review of pharmaceutical galactagogues.
AB  - Use of plant and drug products to enhance lactation is widespread, and numerous
      papers have been published in the medical literature claiming efficacy for
      various products. This paper will review and evaluate the published literature on
      the most widely used pharmaceuticals that are used as galactagogues.
      Breastfeeding physiology is reviewed with the aim of creating a framework for
      understanding galactagogue pharmacology. Published articles were selected and
      evaluated using the principles of evidence-based medicine, and were also
      evaluated using the principles of good lactation management. Only three studies
      on oxytocin and seven studies on dopamine antagonists were found to be useful.
      Oxytocin is probably not useful as a galactagogue, except possibly in rare
      circumstances of tetraplegic mothers. Dopamine antagonists appear not to enhance
      milk supply if mothers are given good lactation support and employ these
      practices. The safety of the dopamine antagonists has not been adequately
      evaluated, so their use should be avoided unless other measures have failed.

PMID- 18081461
TI  - ABM Clinical Protocol #17: Guidelines for breastfeeding infants with cleft lip,
      cleft palate, or cleft lip and palate.

PMID- 18081464
TI  - Distribution of industry-sponsored diaper bags from maternity facilities in
      Massachusetts.

PMID- 18081466
TI  - The moving picture cure: self-therapy documentaries.

PMID- 18081465
TI  - Special issue on film: introduction.

PMID- 18081467
TI  - David Cronenberg's benevolent pathology: technology, trauma, and the perverse
      social link in "Crash".

PMID- 18081468
TI  - Identity as subterfuge: a Kleinian and Winnicottian reading of David Lynch's
      "Mulholland Drive".

PMID- 18081469
TI  - Sexuality, power, and love in Cavani's "The Night Porter": psychological trauma
      and beyond.

PMID- 18081470
TI  - Perversion, fetish, and creativity: the fate of desire in "Utz".

PMID- 18081471
TI  - Moolaade.

PMID- 18081472
TI  - Impersonation of the true self.

PMID- 18081473
TI  - Paranoiac visions and neo-realities in the recent cinema: reflections on Tausk's
      "Influencing Machine in Schizophrenia".

PMID- 18081475
TI  - CyberKnife rhizotomy for facetogenic back pain: a pilot study.
AB  - OBJECT: By targeting the medial branches of the dorsal rami, radiofrequency
      ablation and facet joint injections can provide temporary amelioration of facet
      joint-producing (or facetogenic) back pain. The authors used CyberKnife
      radiosurgery to denervate affected facet joints with the goal of obtaining a less
      invasive yet more thorough and durable antinociceptive rhizotomy. METHODS:
      Patients with refractory low-back pain, in whom symptoms are temporarily resolved
      by facet joint injections, were eligible. The patients were required to exhibit
      positron emission tomography-positive findings at the affected levels.
      Radiosurgical rhizotomy, targeting the facet joint, was performed in a single
      session with a marginal prescription dose of 40 Gy and a maximal dose of 60 Gy.
      RESULTS: Seven facet joints in 5 patients with presumptive facetogenic back pain
      underwent CyberKnife lesioning. The median follow-up was 9.8 months (range 3-16
      months). The mean planning target volume was 1.7 cm(3) (range 0.9-2.7 cm(3)). A
      dose of 40 Gy was prescribed to a mean isodose line of 79% (range 75-80%). Within
      1 month of radiosurgery, improvement in pain was observed in 3 of the 5 patients
      with durable responses at 16, 12, and 6 months, respectively, of follow-up. Two
      patients, after 12 and 3 months of follow-up, have neither improved nor worsened.
      No patient has experienced acute or late-onset toxicity. CONCLUSIONS: These
      preliminary results suggest that CyberKnife radiosurgery could be a safe,
      effective, and non-invasive alternative to radiofrequency ablation for managing
      facetogenic back pain. No patient suffered recurrent symptoms after radiosurgery.
      It is not yet known whether pain relief due to such lesions will be more durable
      than that produced by alternative procedures. A larger series of patients with
      long-term follow-up is ongoing.

PMID- 18081476
TI  - Multisession CyberKnife radiosurgery for optic nerve sheath meningiomas.
AB  - Optic nerve sheath meningiomas (ONSMs) are benign lesions originating from the
      dural sheath of the optic nerve. Progressive growth can lead to gradual loss of
      vision and exophthalmos. Loss of vision following microsurgical resection is not
      uncommon, and although stereotactic fractionated radiotherapy can be a safe
      alternative to control tumor growth and preserve vision, it may also lead to
      complications. Frame-based stereotactic radiosurgery has only been rarely used
      because single-fraction high-dose treatments of intrinsic optic nerve lesions may
      induce unacceptably high toxicity. New frameless radiosurgery devices such as the
      robotic CyberKnife, an image-guided radiosurgery system, can provide the
      extremely tight conformality and submillimetric accuracy of frame-based systems
      combined with the possibility of delivering radiation in several sessions. In the
      present report the authors review the clinical presentation and management of
      ONSMs and describe their preliminary experience using multisession radiosurgery
      to treat these lesions.

PMID- 18081477
TI  - Role of Gamma Knife surgery in the management of pineal region tumors.
AB  - OBJECT: Increasingly, radiosurgery is used to treat pineal region tumors, either
      as a primary treatment or as an adjunct to conventional radiation therapy. The
      authors report their experience with Gamma Knife surgery (GKS) for the treatment
      of pineal region tumors. METHODS: The authors retrospectively reviewed the charts
      of all patients undergoing GKS at their institution between 1997 and 2005.
      Seventeen patients underwent GKS for nonmetastatic tumors of the pineal region.
      All patients were treated using Leksell Gamma Plan treatment planning software
      (versions 4.12::5.34). The mean treatment volume was 7.42 cm(3) (range 1.2-32.5
      cm(3)). Prescribed doses ranged from 12 to 18 Gy. All doses were prescribed to
      the 50% isodose line. Independent neuroradiologists reviewed all follow-up
      imaging studies for evidence of progression of disease. RESULTS: One patient
      (Case 10) died 6 days after GKS. Mean clinical and imaging follow-up in the
      remaining 16 cases was 31 months. Local control was established during a mean
      neuroimaging follow-up period of 31 months (range 1-95) in 16 patients (100%). In
      2 of these 16 patients (one with an anaplastic astrocytoma, the other with a
      primitive neuroectodermal tumor), leptomeningeal and spinal spread of tumor
      developed despite control of the pineal lesions. There were no new neurological
      deficits attributable to GKS. Three patients died (including the one who died 6
      days after GKS) during the follow-up period. Conclusions Excellent control of
      pineal region brain tumors can be obtained with GKS when it is used in
      conjunction with surgery, conventional radiation therapy, or both. Patient
      survival and quality of life can be optimized through the use of multimodal
      treatment, including surgery, conventional radiation therapy and/or radiosurgery,
      and chemotherapy, when applicable.

PMID- 18081478
TI  - Irradiation of glomus jugulare tumors: a historical perspective.
AB  - Glomus jugulare tumors are rare, slow-growing vascular lesions that arise from
      the chief cells of the paraganglia within the jugular bulb. They can be
      associated with the tympanic branch of the glossopharyngeal nerve (Jacobsen
      nerve) or the auricular branch of the vagus nerve (Arnold nerve) and are also
      referred to as chemodectomas or nonchromaffin paragangliomas. Optimal treatment
      of these histologically benign tumors remains controversial. Surgery remains the
      treatment of choice, but can carry high morbidity rates. External-beam radiation
      was originally used for subtotal resections and in patients who were poor
      surgical candidates; however, radiosurgery has recently been introduced as an
      effective and safe treatment option for patients with these tumors. In this
      article the authors discuss the history of radiation therapy for glomus jugulare
      tumors, focusing on recent radiosurgical results.

PMID- 18081479
TI  - Stereotactic radiosurgery for Cushing disease: a review.
AB  - A contemporary review of the use of stereotactic radiosurgery in the treatment of
      Cushing disease (CD) is presented with information drawn from a literature review
      and from the author's experience. Stereotactic radiosurgery is an effective and
      safe therapeutic alternative for treating CD in carefully selected cases.
      Improvements in imaging, dose planning, and general understanding of radiobiology
      are likely to yield better results in the future.

PMID- 18081480
TI  - Stereotactic radiosurgery for functional disorders.
AB  - Stereotactic radiosurgery (SRS) with the Gamma Knife and linear accelerator has
      revolutionized neurosurgery over the past 20 years. The most common indications
      for radiosurgery today are tumors and arteriovenous malformations of the brain.
      Functional indications such as treatment of movement disorders or intractable
      pain only contribute a small percentage of treated patients. Although SRS is the
      only noninvasive form of treatment for functional disorders, it also has some
      limitations: neurophysiological confirmation of the target structure is not
      possible, and one therefore must rely exclusively on anatomical targeting.
      Furthermore, lesion sizes may vary, and shielding adjacent radiosensitive neural
      structures may be difficult or impossible. The most common indication for
      functional SRS is the treatment of trigeminal neuralgia. Radiosurgical treatment
      for epilepsy and certain psychiatric illnesses is performed in several centers as
      part of strict research protocols, and radiosurgical pallidotomy or medial
      thalamotomy is no longer recommended due to the high risk of complications.
      Radiosurgical ventrolateral thalamotomy for the treatment of tremor in patients
      with Parkinson disease or multiple sclerosis, as well as in the treatment of
      essential tremor, may be indicated for a select group of patients with advanced
      age, significant medical conditions that preclude treatment with open surgery, or
      patients who must receive anticoagulation therapy. A promising new application of
      SRS is high-dose radiosurgery delivered to the pituitary stalk. This treatment
      has already been successfully performed in several centers around the world to
      treat severe pain in patients with end-stage cancer.

PMID- 18081481
TI  - Contemporary methods of radiosurgery treatment with the Novalis linear
      accelerator system.
AB  - Radiosurgery has emerged as an indispensable component of the multidisciplinary
      approach to neoplastic, functional, and vascular diseases of the central nervous
      system. In recent years, a number of newly developed integrated systems have been
      introduced for radiosurgery and fractionated stereotactic radiotherapy
      treatments. These modern systems extend the flexibility of radiosurgical
      treatment in allowing the use of frameless image-guided radiation delivery as
      well as high-precision fractionated treatments. The Novalis linear accelerator
      system demonstrates adequate precision and reliability for cranial and
      extracranial radiosurgery, including functional treatments utilizing either frame
      based or frameless image-guided methods.

PMID- 18081482
TI  - Proton radiosurgery in neurosurgery.
AB  - OBJECT: Photon energy deposition from gamma or photon sources follows the law of
      exponential decay. Consequently, energy is deposited over the entire path of the
      radiation beam, resulting in dose distribution before and after the target is
      reached. In contrast, the physical properties of protons are such that energy
      deposition occurs with no exit dose beyond the target volume. Therefore, relative
      to photons, proton beams represent a superior platform for the administration of
      radiosurgery. METHODS: In this review, the authors will discuss the fundamental
      principles underlying photon- and proton-based stereotactic radiosurgery (SRS).
      The clinical efficacy of proton-based SRS in the treatment of arteriovenous
      malformations, vestibular schwannomas, and pituitary adenomas is reviewed.
      RESULTS: Direct comparisons of clinical results attained using photon- and proton
      based SRS are confounded by a bias toward reserving proton beams for the
      treatment of larger and more complex lesions. Despite this bias, the clinical
      outcomes for proton-based SRS have been excellent and have been at least
      comparable to those for photon-based treatments. CONCLUSIONS: The physical
      properties of proton radiation offer superior conformality in dose distribution
      relative to photon irradiation. This advantage becomes more apparent as the
      lesion size increases and will probably be magnified with the development of
      intensity-modulated proton techniques.

PMID- 18081483
TI  - Robotics and its applications in stereotactic radiosurgery.
AB  - Stereotactic radiosurgery has undergone a remarkable evolution since its
      conception and the subsequent introduction of image-guided radiosurgery,
      primarily because of the concurrent advances in imaging and computer technology.
      However, recent improvements in real-time imaging, inverse planning techniques,
      and frameless alternatives have greatly enhanced the conformity and accuracy of
      the radiosurgical procedure. As a consequence, the possibility of
      hypofractionation is offered, and both intra- and extracranial targets can now be
      ablated with sustained submillimetric precision. Although all indispensable
      features, none is as impressive or useful as the incorporation of robotics,
      robotic beam delivery, or robotic-assisted planning, which has only served to
      improve the accuracy and homogeneity of therapy. The aim of this article was to
      describe the general technological basis of robots in radiosurgery and to review
      current clinical usage of robotic radiosurgery devices. Emphasis has been placed
      on robotic principles and the various popular applications currently available.

PMID- 18081484
TI  - Advances in the radiosurgical treatment of large inoperable arteriovenous
      malformations.
AB  - Radiosurgery has proven useful in the treatment of small arteriovenous
      malformations (AVMs) of the brain. However, the volume of healthy tissue
      irradiated around large lesions is rather significant, necessitating reduced
      radiation doses to avoid complications. As a consequence, this can produce poorer
      obliteration rates. Several strategies have been developed in the past decade to
      circumvent dose-volume problems with large AVMs, including repeated treatments as
      well as dose, and volume fractionation schemes. Although success on par with that
      achieved in lesions smaller than 3 ml remains elusive, improvements over the
      obliteration rate, the complication rate or both have been reported after
      conventional single-dose stereotactic radiosurgery (SRS). Radiosurgery with a
      marginal dose or peripheral dose < 15 Gy rarely obliterates AVMs, yet most
      lesions diminish in size posttreatment. Higher doses may then be reapplied to any
      residual nidi after an appropriate follow-up period. Volume fractionation divides
      AVMs into smaller segments to be treated on separate occasions. Doses > 15 Gy
      irradiate target volumes of only 5-15 ml, thereby minimizing the radiation
      delivered to the surrounding brain tissue. Fewer adverse radiological effects
      with the use of fractionated radiosurgery over standard radiosurgery have been
      reported. Advances in AVM localization, dose delivery, and dosimetry have revived
      interest in hypofractionated SRS. Investigators dispensing >or= 7 Gy per fraction
      minimum doses have achieved occlusion with an acceptable number of complications
      in 53-70% of patients. The extended latency period between treatment and
      occlusion, about 5 years for emerging techniques (such as salvage, staged volume,
      and hypofractionated radiotherapy), exposes the patient to the risk of hemorrhage
      during that period. Nevertheless, improvements in dose planning and target
      delineation will continue to improve the prognosis in patients harboring
      inoperable AVMs.

PMID- 18081485
TI  - Gamma Knife stereotactic radiosurgical treatment of idiopathic trigeminal
      neuralgia: long-term outcome and complications.
AB  - OBJECT: Stereotactic radiosurgery (SRS) with the Gamma Knife (GK) is a rapidly
      emerging surgical modality in the management of medically refractory idiopathic
      trigeminal neuralgia (TN). The current study examines the long-term outcome in
      patients with drug-resistant idiopathic TN who underwent GK surgery at the
      authors' institution. METHODS: One hundred and six consecutive patients (38 men
      and 68 women) with proven medically refractory idiopathic TN were included in
      this retrospective study. Their ages were 41-82 years (mean 72.3 years). All
      patients underwent SRS with prescribed maximal radiation doses ranging from 70 to
      85 Gy. Isocenters 1-3 were used and plugging was used selectively. The follow-up
      period was 12-72 months (mean 34.3 months). The patients were divided into 2
      groups according to their history of previous surgery. RESULTS: The initial
      response rate in patients with no history of previous surgery was 92.9%; in those
      who had undergone previous surgery, the initial response rate was 85.7%. At the
      end of the 1st posttreatment year, an excellent outcome was achieved in 82.5% of
      patients who had not had previous surgery, and in 69.4% of those who had. The
      respective outcome rates for the 2nd posttreatment year were 78 and 63.5%,
      respectively. The most common complication was the development of persistent
      paresthesia, which occurred in 15.8% of patients with no previous surgery and
      16.3% of those with previous surgery. CONCLUSIONS: Stereotactic radiosurgery with
      the GK is a safe and effective treatment option for patients with medically
      refractory idiopathic TN.

PMID- 18081486
TI  - CyberKnife radiosurgical rhizotomy for the treatment of atypical trigeminal nerve
      pain.
AB  - OBJECT: Patients with atypical trigeminal neuralgia (TN) have unilateral pain in
      the trigeminal distribution that is dull, aching, or burning in nature and is
      constant or nearly constant. Studies of most radiosurgical and surgical series
      have shown lower response rates in patients with atypical TN. This study
      represents the first report of the treatment of atypical TN with frameless
      CyberKnife stereotactic radiosurgery (SRS). METHODS: Between 2002 and 2007, 7
      patients that satisfied the criteria for atypical TN and underwent SRS were
      included in our study. A 6-8-mm segment of the trigeminal nerve was targeted,
      excluding the proximal 3 mm at the brainstem. All patients were treated in a
      single session with a median maximum dose of 78 Gy and a median marginal dose of
      64 Gy. RESULTS: Outcomes in 7 patients with a mean age of 61.6 years and a median
      follow-up of 20 months are reported. Following SRS, 4 patients had complete pain
      relief, 2 had minimal pain relief with some decrease in the intensity of their
      pain, and 1 patient experienced no pain relief. Pain relief was reported within 1
      week of SRS in 4 patients and at 4 months in 2 patients. After a median follow-up
      of 28 months, pain did not recur in any of the 4 patients who had reported
      complete pain relief. Complications after SRS included bothersome numbness in 3
      patients and significant dysesthesias in 1 patient. CONCLUSIONS: The authors have
      previously reported a 90% rate of excellent pain relief in patients with classic
      TN treated with CyberKnife SRS. Compared with patients with classic TN, patients
      with atypical TN have a lower rate of pain relief. Nevertheless, the nearly 60%
      rate of success after SRS achieved in this study is still comparable to or better
      than results achieved with any other treatment modality for atypical TN.

PMID- 18081487
TI  - Neuroophthalmological evaluation after Gamma Knife surgery for cavernous sinus
      meningiomas.
AB  - OBJECT: Treatment options for patients with cavernous sinus meningiomas (CSMs)
      include microsurgical tumor resection, radiotherapy, and radiosurgery. Gamma
      Knife surgery (GKS) is increasingly being used because it is associated with
      lower mortality and morbidity rates than microsurgery. The purpose of this study
      was to assess the role of GKS in the treatment of CSM and to thoroughly analyze
      the clinical response to GKS. METHODS: Between January 2001 and December 2005,
      123 patients (25 men and 98 women; mean age 62.6 +/- 11 years, range 31-86 years)
      who underwent treatment for CSMs were included in this study. Of these, 41
      patients underwent microsurgery before GKS, whereas the remaining 82 had GKS as a
      first-line therapy after a diagnosis was made based on magnetic resonance imaging
      findings. Dysfunction in cranial nerves (CNs) II, III, IV, V, and VI was noted in
      74 patients at the time of GKS. The mean tumor volume was 7.99 cm(3) (0.7-30.5
      cm(3)). The mean prescription dose to the tumor margin was 13.8 +/- 1.1 Gy (range
      10-20 Gy). RESULTS: The overall tumor control rate was 98.4% with a median follow
      up of 36 months. The actuarial tumor control rate at 5 years was 90.5%. A
      reduction in tumor volume was observed in 53 patients (43.1%), whereas in 68
      patients (55.3%) no volumetric variation was recorded. Of the 74 patients who
      presented with CN deficits, improvement was noted in 23 (31.1%). CONCLUSIONS:
      Gamma Knife surgery is a useful treatment for CSM both as a first- or second-line
      therapy. It is a safe and effective treatment for tumors located close to the
      optic pathways.

PMID- 18081490
TI  - The long haul: risks associated with livestock transport.

PMID- 18081491
TI  - Casting a wider net for countermeasure R&D funding decisions.
AB  - Among potential bioweapons attacks, endemic infectious diseases (that is, those
      naturally occurring diseases that afflict us every year), and a potential
      influenza pandemic, how should we apportion funding and resources for basic
      research and countermeasure development? To address this question, I argue for a
      "combined risk assessment" that considers bioweapons attacks with natural
      pandemics and endemic infectious disease. At present, risk assessments for
      bioweapons attacks are carried out separately from the assessments long carried
      out for endemic infectious diseases to make public health and medical care
      decisions. One result of this separation is that funding decisions may be unduly
      influenced by an overblown fear of a big bioweapons attack and by political whim.
      The result of the simplified combined risk assessment presented here argues for
      more funding and resources for endemic infectious disease and for placing
      biodefense against anthrax and other bioweapons in a place lower in the risk
      hierarchy. Since the assessment here considers only fatalities to make the point
      that our priorities are skewed, the conclusions are only a "first word" on the
      subject, far from the last. Furthermore, the impact of other issues on
      priorities, such as national and international policy, is not considered. It is a
      call for a debate on the public stage of the policy and other rationale and the
      quantitative risk assessment arguments that now place bioweapons attacks at the
      top of our risk ranking.

PMID- 18081492
TI  - Pandemic policy and planning considerations for universities: findings from a
      tabletop exercise.
AB  - The potential for a novel influenza virus to cause a pandemic represents a
      significant threat to global health. Planning for pandemic flu, as compared to
      planning for other types of hazards, presents some unique challenges to
      businesses, communities, and education institutions. To identify and address the
      challenges that may be faced by major metropolitan universities during a flu
      pandemic, a tabletop exercise was developed, offered, and evaluated. Its purpose
      was to assess existing University of Washington (UW) plans and policies for
      responding to an influenza pandemic. On May 31, 2006, more than 50 participants,
      including UW administrators and unit leaders and a number of key external
      partners, participated in a tabletop exercise designed to simulate all phases of
      an influenza pandemic. This exercise revealed existing gaps in university
      pandemic influenza plans and policies, including issues related to isolation and
      quarantine, continuity of operations, disaster mental health services,
      integration of volunteers into a disaster response, tracking travel of university
      students and personnel, communication problems, and ways to meet the needs of
      resident and foreign students and faculty during an outbreak. Policy and planning
      recommendations are offered that address each of these challenges faced by UW as
      well as other major research universities and colleges.

PMID- 18081493
TI  - Community response grids: using information technology to help communities
      respond to bioterror emergencies.
AB  - Access to accurate and trusted information is vital in preparing for, responding
      to, and recovering from an emergency. To facilitate response in large-scale
      emergency situations, Community Response Grids (CRGs) integrate Internet and
      mobile technologies to enable residents to report information, professional
      emergency responders to disseminate instructions, and residents to assist one
      another. CRGs use technology to help residents and professional emergency
      responders to work together in community response to emergencies, including
      bioterrorism events. In a time of increased danger from bioterrorist threats, the
      application of advanced information and communication technologies to community
      response is vital in confronting such threats. This article describes CRGs, their
      underlying concepts, development efforts, their relevance to biosecurity and
      bioterrorism, and future research issues in the use of technology to facilitate
      community response.

PMID- 18081494
TI  - Quantitative impact of mental health preparedness training for public health
      professionals.
AB  - Coordinating and integrating mental health topics into emergency preparedness
      planning is a critical step for ensuring effective response to the psychological
      issues connected with trauma. In order to remedy the current lack of integration,
      potential response providers must receive effective mental health preparedness
      training. The current study provided mental health preparedness training to
      public health and allied health professionals in Kansas and assessed the impact
      of the training on perceived mental health preparedness knowledge. Participants
      included 157 potential first and secondary responders from public health and
      allied fields who attended one of 10 training presentations on mental health
      emergency preparedness. Pre- and post-presentation, participants responded to six
      Likert-scale questions about their perceived knowledge of topics and level of
      mental health preparedness. Questions addressed common psychological responses to
      disaster or terrorist events, stress reactions of specific populations,
      psychological resiliency, mental health preparedness integration, and level of
      agency preparedness. Post-training, participants reported statistically
      significant (p<0.001) increases in perceived level of knowledge on all topics.
      Participants were also significantly more likely (p<0.001) to report that their
      agency could respond to the mental health issues related to a disaster or
      emergency. The current study provides data about gaps in practitioner knowledge
      regarding mental health preparedness in Kansas. While the self-report nature of
      responses is a limitation, these findings serve as the first step toward
      producing and implementing effective mental health preparedness information and
      training on a wide scale.

PMID- 18081496
TI  - Synthetic genomics | options for governance.

PMID- 18081497
TI  - Children should be among the highest priority groups to receive immunization for
      seasonal and pandemic influenza.

PMID- 18081503
TI  - Angiotensin-converting enzyme genotype and successful ascent to extreme high
      altitude.
AB  - Interindividual variation in acclimatization to altitude suggests a genetic
      component, and several candidate genes have been proposed. One such candidate is
      a polymorphism in the angiotensin converting enzyme (ACE) gene, where the
      insertion (I-allele), rather than the deletion (D-allele), of a 287 base pair
      sequence has been associated with lower circulating and tissue ACE activity and
      has a greater than normal frequency among elite endurance athletes and, in a
      single study, among elite high altitude mountaineers. We tested the hypothesis
      that the I-allele is associated with successful ascent to the extreme high
      altitude of 8000 m. 141 mountaineers who had participated in expeditions
      attempting to climb an 8000-m peak completed a questionnaire and provided a
      buccal swab for ACE I/D genotyping. ACE genotype was determined in 139
      mountaineers. ACE genotype distribution differed significantly between those who
      had successfully climbed beyond 8000 m and those who had not (p = 0.003), with a
      relative overrepresentation of the I-allele among the successful group (0.55 vs.
      0.36 in successful vs. unsuccessful, respectively). The I-allele was associated
      with increased maximum altitudes achieved: 8079 +/- 947 m for DDs, 8107 +/- 653 m
      for IDs, and 8559 +/- 565 m for IIs (p = 0.007). There was no statistical
      difference in ACE genotype frequency between those who climbed to over 8000 m
      using supplementary oxygen and those who did not (p = 0.267). This study
      demonstrates an association between the ACE I-allele and successful ascent to
      over 8000 m.

PMID- 18081504
TI  - Hematological and lipid profile changes in sea-level natives after exposure to
      3550-m altitude for 8 months.
AB  - The aim of this epidemiological study was to determinate the effects on
      hematological and lipid profile in a young group of newcomers to altitude after
      being exposed chronically for 8 months to 3550 m (n = 50), age 17.8 +/- 0.7; and
      not overweight, BMI 22.9 +/- 0.5). Readings taken at altitude on day 1 and on
      month 8 were hematocrit (Hct, %), hemoglobin (Hb, g/dL), Sa(O(2)), total
      leukocyte and subset count (mm(3), %), and lipid profile (mg/dL). The same
      measurements were taken in a comparative group (CG) at sea level (SL). At
      altitude, elevations of Hct (44.6 +/- 0.4; 51.2 +/- 0.4) and Hb (15.5 +/- 0.1;
      17.3 +/- 0.1) were seen (p < 0.001) and none with Hb >/= 21 g/dL. No correlation
      was observed between Hb and Sa(O(2)), r = 0.11, p > 0.05. Total leukocyte count
      showed no changes (6037 +/- 74; 6002 +/- 43), but a relative neutropenia (55.2 + 
      1.5; 50.6 + -1.3) and lymphocytosis (34.2 + 1; 42.4 + 1, p < 0.001) between
      periods were found and also when compared to SL. Also, an inverse relationship
      between Sa(O(2)) and total leukocytes on month 8 (r = 0.46; r(2) = 0.204),
      suggesting a probable representation of a hypoxia effect. Total cholesterol
      (153.8 +/- 4.5; 157.3 +/- 5.1; p, ns) showed no changes, but a mild decrease of
      LDL-cholesterol (88.4 +/- 3.3; 81.0 +/- 3.9; p < 0.05), and a rise in
      triglycerides (121.6 +/- 10.9; 178.8 +/- 11.7; p < 0.001) was found. Changes
      observed in leukocytes subset count and triglycerides could suggest a
      contributory role of hypoxic conditions, raising some future epidemiological
      concerns regarding immune system and fatty acid behaviour at altitude.

PMID- 18081505
TI  - Arterial oxygen saturation and hemoglobin mass in postmenopausal untrained and
      trained altitude residents.
AB  - Because of lacking ventilatory stimulation by sex hormones in postmenopausal
      women (PW), one might expect a lowered arterial oxygen saturation (S(O(2))) in
      hypoxia and therefore a stronger erythropoietic reaction than in young women
      (YW). Nine untrained (UTRPW) and 11 trained (TRPW) postmenopausal altitude
      residents (2600 m) were compared to 16 untrained (UTRYW) and 16 trained young
      women (TRYW) to check this hypothesis and to study the combined response to
      hypoxia and training. S(O(2)) was decreased in PW (89.2% +/- 2.2 vs. 93.6 +/-
      0.7% in YW, p < 0.01). Hb mass, however, was similar in UT (UTRYW: 9.2 +/- 0.9
      g/kg(1), UTRPW: 8.7 +/- 1.0 g/kg). But if body fat rise with age was excluded by
      relation to fat-free mass, Hb mass was increased in UTRPW (+1.2 g/kg, p < 0.05)
      compared to UTRYW. Training caused a similar rise of Hb mass in PW and YW (0.3
      g/kg per mL/kg x min(1) rise in V(O(2peak))). There was no difference in
      erythropoietin among the groups. Ferritin was higher in PW than YW. The results
      show that female hormones and fitness level have to be considered in studies on
      erythropoiesis at altitude. The role of erythropoietin during chronic hypoxia
      still has to be clarified.

PMID- 18081506
TI  - Residents at high altitude show a lower glucose profile than sea-level residents
      throughout 12-hour blood continuous monitoring.
AB  - It is known that residents at high altitude (HA) have a lower basal glycemia than
      residents at sea level (SL). However, whether such a difference is maintained
      throughout the full day remains unknown. We compared 12-h blood glucose profiles
      from 10 healthy males native residents at HA (3250 m) and 8 male residents at SL.
      Glucose profile at HA was lower throughout the glucose monitoring than that at SL
      (mean profile: 50.6 +/- 3.7 and 73.4 +/- 4.0 mg/dL, respectively; p < 0.001).
      Basal and postprandial insulin and triacylglycerol values were similar in both
      groups. In conclusion, HA natives resident have a lower blood glucose profile
      than SL residents throughout 12-h continuous monitoring.

PMID- 18081507
TI  - Acute hypobaric hypoxia (5486 m) induces greater pulmonary HIF-1 activation in
      hilltop compared to madison rats.
AB  - Compared to Madison strain Sprague-Dawley rats, the Hilltop strain is resistant
      to acute hypoxic pulmonary vasoconstriction and pulmonary leak, a pathology
      resembling high altitude pulmonary edema (HAPE) in humans. Hypoxia inducible
      transcription factor-1 (HIF-1) mediates transcription of proteins that can
      "rescue" tissue from hypoxia, including vasoactive and angiogenic proteins such
      as inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor
      (VEGF). Because these proteins have theoretical relevance to the etiology of
      HAPE, we hypothesized that hypoxia-resistant Hilltop rats acutely exposed to high
      altitude would have greater HIF-1 activity and expression of iNOS and VEGF as
      compared to hypoxia-sensitive Madison rats. Animals were exposed to normobaric
      normoxia or hypobaric hypoxia (18 h at 5486 m). The presence of nuclear HIF-1
      heterodimer subunits, HIF-1-DNA binding, and iNOS and VEGF protein expression
      were determined in lung tissue. Hypoxic HIF-1beta expression, HIF-1-DNA binding,
      and iNOS and VEGF expression were greater in Hilltop than in Madison rats. After
      18-h hypobaric hypoxia, HIF-1 activity and HIF-mediated protein expression were
      elevated in Hilltop rats, but not in Madison rats. To our knowledge, this is the
      first report of differing HIF-1 activation between two strains of animals with
      clearly divergent physiological responses to identical hypoxic conditions.

PMID- 18081508
TI  - Capillary supply and fiber morphometry in rat myocardium after intermittent
      exposure to hypobaric hypoxia.
AB  - Three groups of male rats were submitted to an intermittent hypobaric hypoxia
      (IHH) program for 22 days (4 h/day, 5 days/week) in a hypobaric chamber at a
      simulated altitude of 5000 m. Hearts were removed at the end of the program (H
      group) and 20 and 40 days later (P20 and P40 groups). A control group (C) was
      maintained at sea-level pressure. Transverse sections from myocardium were cut
      and histochemically stained in order to measure fiber morphometry and
      capillaries. We observed a progressive increase from C to H to P20 animals in
      capillary (4124 to 4733 to 4816 capillaries/mm(2)) and fiber densities (2844 to
      3125 to 3284 fibers/mm(2)) associated with significant reductions in fiber area
      (273, 235, and 227 microm(2)), perimeter (69, 64, and 62 microm), and diffusion
      distances (18.2, 16.9, and 16.6 microm). The most significant differences between
      C and hypoxic groups were found when morphometrical and vascular fiber parameters
      were combined. The myocardium of the latter had more capillaries per fiber area
      and per fiber perimeter. These findings indicate that the IHH program elicits an
      adaptive response of rat myocardium to a more efficient O2 delivery to
      mitochondria of cardiac muscle cells. Capillarization and fiber morphometric
      changes showed marked differences over time. In all cases, P20 had higher
      capillarization parameters and fiber morphometry reductions than H, thus
      indicating that a delay of about 20 days exists after the hypoxic stimulus ceases
      to reach complete angiogenesis and fiber morphometry changes. However, P40
      animals showed a recovery to basal values of the parameters related to fiber
      morphometry (area, perimeter, and diffusion distances), but maintained high
      capillarity values (capillary density, NCF, CCA, CCP).

PMID- 18081509
TI  - Evidence for increased intracranial pressure in high altitude pulmonary edema.
AB  - We sought to determine if optic nerve sheath diameter (ONSD), a surrogate measure
      of ICP, is increased in high altitude pulmonary edema (HAPE). Five HAPE patients
      (one with a codiagnosis of high altitude cerebral edema [HACE]) treated at the
      Himalayan Rescue Association clinic in Pheriche, Nepal (4240 m), underwent optic
      nerve sheath ultrasonography (ONSU) at admission to determine ONSD. Results were
      compared to ONSD in 32 control subjects at the same altitude without evidence of
      altitude illness. Four of the five HAPE patients underwent repeat ONSU at
      discharge. All exams were read by two blinded observers. The mean ONSD for HAPE
      patients on presentation was 5.7 +/- 0.44 mm and for controls was 4.7 +/- 0.56 mm
      (p = 0.003). Excluding the patient with a coexistent clinical diagnosis of HACE,
      mean ONSD at presentation for the other four HAPE patients was 5.7 +/- 0.50 mm
      and was significantly different from controls (p = 0.007). In the four HAPE
      patients with repeat exams, ONSD decreased by 17% +/- 15% (95% CI 4-30%) between
      admission and discharge. We conclude that HAPE is associated with increased ONSD,
      a surrogate measure of increased ICP.

PMID- 18081510
TI  - High altitude and retinal detachment.
AB  - We describe the case of a 38-year-old man who presented with bilateral retinal
      detachments following a trek in Tibet during which time he took acetazolamide for
      prophylaxis of acute mountain sickness (AMS). This is the first time that retinal
      detachment has been described following a sojourn to high altitude. Acetazolamide
      has not been previously associated with retinal detachment when used for
      prophylaxis of AMS or indeed during its many ophthalmic applications. The patient
      made a good recovery following surgery, and we speculate that, although this
      could be coincidental and the patient did have risk factors for retinal
      detachment, the possibility of a causal link to high altitude should at least be
      entertained. We hypothesize that vitreous dehydration may have caused
      vitreoretinal traction and that hypobaric hypoxia may have changed the dynamic
      relationship between vitreous, retina, retinal pigment epithelium (RPE) and
      choroid, causing preexisting retinal holes to open, allowing subretinal fluid to
      accumulate and detach the retina.

PMID- 18081511
TI  - Arterial thrombosis at high altitude resulting in loss of limb.
AB  - Vascular thrombosis is an uncommon but recognized peril of high altitude travel.
      Traditionally, this has been associated with prolonged exposure to extreme
      altitudes where dehydration, hemoconcentration, cold, use of constrictive
      clothing, and enforced stasis due to severe weather have been named as
      contributing factors. It is widely hypothesized that hypoxia itself alters the
      coagulation cascade to create a prothrombotic milieu, though evidence thus far is
      limited and frequently conflicting. Case reports have described venous
      thrombosis, pulmonary embolism, cerebrovascular accidents, transient ischemic
      attacks, and thromboses of the portal circulation at altitude. We report a unique
      case of aortic thrombosis presenting with critical lower extremity ischemia in a
      previously healthy individual after a brief exposure to altitudes up to 4620 m.
      None of the frequently invoked risk factors of dehydration, cold, enforced use of
      constrictive clothing, weather-imposed inactivity, or extreme altitude were
      present, and no medical predisposition to thrombosis was identified, suggesting
      hypoxia as the most likely prothrombotic stimulus. We discuss the treatment of
      this problem and the application of Doppler ultrasonography in a wilderness
      setting.

PMID- 18081514
TI  - Adjuvant therapy for unresectable meningiomas: benign and malignant.

PMID- 18081517
TI  - Veterinary medicine, global health.

PMID- 18081518
TI  - What is your diagnosis? Tarsometatarsal subluxation.

PMID- 18081519
TI  - Employment, starting salaries, and educational indebtedness of year-2007
      graduates of US veterinary medical colleges.

PMID- 18081520
TI  - Myths and misconceptions in veterinary dentistry.

PMID- 18081522
TI  - Assessment of anemia as an independent predictor of response to chemotherapy and
      survival in dogs with lymphoma: 96 cases (1993-2006).
AB  - OBJECTIVE: To determine whether the presence of anemia (Hct < or = 37%) at the
      time of diagnosis of lymphoma is a negative prognostic indicator for response to
      treatment and survival time in dogs that are undergoing chemotherapy. DESIGN:
      Retrospective case series. Animals-96 dogs with lymphoma that were receiving
      chemotherapy. Procedures-Information regarding signalment, initial hematologic
      data, chemotherapy protocol, clinical response, and date of death was
      retrospectively collected from medical records of dogs with lymphoma. Univariate,
      multivariate, and survival analyses were performed to determine the effect of
      anemia on initial response to chemotherapy and on survival time. RESULTS:
      Overall, dogs without anemia (n = 56) were 4 times as likely as dogs with anemia
      (40) to have a complete response following chemotherapy. Anemic dogs had a
      significantly shorter median survival time (139 days), compared with survival
      time of nonanemic dogs (315 days). Subset analysis of dogs with multicentric
      lymphoma (matched for clinical stage and chemotherapy protocol) revealed that the
      dogs with anemia (n = 24) had a significantly shorter median survival time (101
      days), compared with survival time of dogs without anemia (24; 284 days). Other
      variables were not associated with survival time. CONCLUSIONS AND CLINICAL
      RELEVANCE: These findings suggested that anemia is a negative prognostic factor
      for dogs with lymphoma that are undergoing chemotherapy. Further investigation
      will be necessary to determine the impact of resolution of anemia on clinical
      outcome in dogs with lymphoma.

PMID- 18081523
TI  - Prevalence, clinical features, and causes of epistaxis in dogs: 176 cases (1996
      2001).
AB  - OBJECTIVE: To determine prevalence, clinical features, and causes of epistaxis in
      dogs. DESIGN: Retrospective case series. ANIMALS: 176 dogs with epistaxis.
      PROCEDURES: Medical records were reviewed for information related to signalment,
      clinical features, diagnosis, and outcome. RESULTS: 132 (75%) dogs were initially
      examined by the hospital's emergency service; prevalence of epistaxis was 0.3%.
      Dogs with epistaxis were more likely to be old (> or = 6 years), male, and large
      (> or = 26 kg [58.5 lb]) than were dogs in a reference population. In 109 (62%)
      dogs with epistaxis, an underlying cause was identified; 115 underlying disorders
      were identified, with 90 classified as local and 25 classified as systemic. Local
      causes of epistaxis included nasal neoplasia (n = 35), trauma (33), idiopathic
      rhinitis (20), and periapical abscess (2). Systemic causes included
      thrombocytopenia (12), thrombocytopathia (7), coagulopathy (3), hypertension (2),
      and vasculitis (1). Dogs with local causes were more likely to have unilateral
      than bilateral epistaxis, but 11 of 21 (52%) dogs with systemic disorders also
      had unilateral epistaxis. Dogs with systemic disorders were more likely to have
      clinical signs of systemic disease. Duration of epistaxis (acute vs chronic),
      severity, and duration of hospitalization were similar for dogs with local versus
      systemic disorders. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that
      epistaxis was a common disorder in dogs and frequently regarded as an emergency.
      Local causes of epistaxis were predominant, but clinical features traditionally
      thought to be helpful in distinguishing local versus systemic causes could not be
      reliably used for this purpose.

PMID- 18081524
TI  - Hemangiosarcoma in cats: 53 cases (1992-2002).
AB  - OBJECTIVE: To characterize the biological behavior and prognostic factors
      associated with hemangiosarcoma in cats. DESIGN: Retrospective case series.
      ANIMALS: 53 cats with hemangiosarcoma. PROCEDURES: Data were retrieved from a
      state veterinary diagnostic laboratory, 3 veterinary colleges, and a private
      practice. RESULTS: Cutaneous and subcutaneous tumor locations were more common
      than visceral (abdominal and thoracic) and oral locations. Surgical excision was
      the primary treatment in 47 cats. Tumor-free surgical margins were more likely in
      cutaneous than subcutaneous lesions and were associated with longer survival
      times. Local recurrence was observed in 6 of 12 cats with subcutaneous lesions
      for which follow-up was available. Metastatic disease was detected in 5 of 13
      cats with adequate staging at initial diagnosis. A sixth cat had pulmonary
      metastases at the time of euthanasia. In 4 of 10 cats with visceral
      hemangiosarcoma, the diagnosis was made at necropsy or they were euthanized at
      the time of diagnosis. Adjuvant therapy was uncommonly used. Eighteen of the 21
      known deaths or euthanasias were tumor-related. Higher mitotic counts (> 3 in 10
      hpfs) were associated with shorter survival times. CONCLUSIONS AND CLINICAL
      RELEVANCE: Subcutaneous hemangiosarcoma was more biologically aggressive than the
      cutaneous form and was more likely to recur locally and result in euthanasia or
      death of the cat. Metastatic potential of the cutaneous and subcutaneous forms
      may be greater than previously reported. Visceral hemangiosarcoma is associated
      with a grave prognosis.

PMID- 18081525
TI  - A multicenter case-control study of risk factors for equine protozoal
      myeloencephalitis.
AB  - OBJECTIVE: To identify risk factors for equine protozoal myeloencephalitis (EPM)
      among horses examined at 11 equine referral hospitals. DESIGN: Case-control
      study. ANIMALS: 183 horses with EPM, 297 horses with neurologic disease other
      than EPM (neurologic controls), and 168 horses with non-neurologic diseases (non
      neurologic controls) examined at 11 equine referral hospitals in the United
      States. PROCEDURES: A study data form was completed for all horses. Data were
      compared between the case group and each of the control groups by means of
      bivariate and multivariate polytomous logistic regression. RESULTS: Relative to
      neurologic control horses, case horses were more likely to be > or = 2 years old
      and to have a history of cats residing on the premises. Relative to non
      neurologic control horses, case horses were more likely to be used for racing or
      Western performance. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that
      cats may play a role in the natural epidemiology of EPM, that the disease is less
      common among horses < 2 years of age relative to other neurologic diseases, and
      that horses used for particular types of competition may have an increased risk
      of developing EPM.

PMID- 18081527
TI  - Effect of repeated administration of oxytocin during diestrus on duration of
      function of corpora lutea in mares.
AB  - OBJECTIVE: To determine whether IM administration of exogenous oxytocin twice
      daily on days 7 to 14 after ovulation blocks luteolysis and causes prolonged
      function of corpora lutea (CL) in mares. DESIGN: Prospective study. ANIMALS: 12
      mares. PROCEDURES: Beginning on the day of ovulation (day 0), jugular blood
      samples were collected every other day until day 40 for determination of
      progesterone concentration. On day 7, mares (n = 6/group) were treated with
      saline (0.9% NaCl) solution (control group) or oxytocin. Beginning on day 7,
      control mares received 3 mL of sterile saline solution every 12 hours, IM, and
      oxytocin-treated mares received 60 units of oxytocin every 12 hours, IM, through
      day 14. Mares were considered to have prolonged CL function if progesterone
      concentration remained > 1.0 ng/mL continuously through day 30. RESULTS: The
      proportion of mares with prolonged CL function was significantly higher in the
      oxytocin-treated group (6/6), compared with the control group (0/6). All control
      mares underwent luteolysis by day 16, at which time their progesterone
      concentrations were < 1.0 ng/mL. In contrast, all 6 oxytocin-treated mares
      maintained progesterone concentrations > 1.0 ng/mL continuously through day 30.
      CONCLUSIONS AND CLINICAL RELEVANCE: IM administration of 60 units of oxytocin
      twice daily on days 7 to 14 after ovulation was an efficacious method of
      inhibiting luteolysis and extending CL function in mares. Disrupting luteolysis
      by administering exogenous oxytocin during diestrus appears to be a plausible and
      practical method of long-term suppression of estrus in mares.

PMID- 18081528
TI  - Transendoscopic, laser-assisted ventriculocordectomy for treatment of left
      laryngeal hemiplegia in horses: 22 cases (1999-2005).
AB  - OBJECTIVE: To determine long-term effects of transendoscopic, laser-assisted
      ventriculocordectomy (LAVC) on airway noise and performance in horses with
      naturally occurring left laryngeal hemiplegia. DESIGN: Retrospective case series.
      ANIMALS: 22 horses with left laryngeal hemiplegia treated by means of LAVC.
      PROCEDURES: Medical records were reviewed and initial complaint, intended use of
      the horse, duration of abnormal airway noise, preoperative performance level,
      endoscopic findings, surgical procedure, postoperative treatment, and
      complications were recorded. Follow-up telephone interviews with owners and
      trainers were conducted to determine time for return to intended use, level of
      postoperative performance, and percentage reduction in airway noise. RESULTS: All
      horses were examined because of excessive airway noise; 10 (45%) had concurrent
      exercise intolerance. Left ventriculocordectomy was performed in all 22 horses;
      bilateral ventriculocordectomy (right ventriculocordectomy was done 1 year later)
      was performed in 1 horse (5%). Complications occurred in 3 (14%) horses. Twenty
      (91%) horses returned to their intended use. Excessive airway noise was
      eliminated after surgery in 18 (82%) horses; exercise intolerance improved
      postoperatively in 8 of 10 horses. Three racing Thoroughbreds returned to racing;
      1 additional racehorse returned to racing but required a laryngoplasty 1 year
      later to continue racing. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested
      that LAVC was an effective procedure for elimination of excessive airway noise
      and improvement of performance in horses with left laryngeal hemiplegia.

PMID- 18081529
TI  - Effect of passive transfer status on preweaning growth performance in dairy goat
      kids.
AB  - OBJECTIVE: To evaluate the effect of passive transfer status (determined from
      measurements of serum IgG concentration at 24 hours after parturition [sIgG-24])
      on preweaning growth performance in dairy goat kids. DESIGN: Prospective
      observational study. ANIMALS: 20 healthy nursing dairy doe kids in a natural
      nonintensive breeding environment. PROCEDURES: For each kid, sIgG-24 was
      measured. Body weight was measured at birth and at the time of weaning 30 days
      (ie, 29 to 31 days) after birth; average daily gain from birth to day 30 and
      weight at day 30 were used as measures of preweaning growth performance.
      Regression analysis was used to evaluate associations between sIgG-24 and
      measures of preweaning growth performance. RESULTS: Mean +/- SD sIgG-24 was 31.7
      +/- 10.3 mg/mL. Mean body weights at birth and weaning were 4.105 +/- 0.981 kg
      (9.031 +/- 2.158 lb) and 9.310 +/- 2.554 kg (20.482 +/- 5.619 lb), respectively;
      average daily gain was 0.174 +/- 0.072 kg/d (0.383 +/- 0.158 lb/d). No
      significant association was detected between sIgG-24 and birth weight. However,
      sIgG-24 was significantly associated with average daily gain (R(2) = 0.48) and
      weight at day 30 (R(2) = 0.56). Each increase in sIgG-24 of 1 mg/mL was
      associated with an increase in average daily gain of 0.005 kg/d (0.011 lb/d) and
      an increase in weight at day 30 of 0.185 kg (0.407 lb). CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that passive transfer status (determined as sIgG-24)
      was a significant source of variation in preweaning growth performance in dairy
      doe kids reared in this nonintensive breeding environment.

PMID- 18081530
TI  - Naturally transmitted herpesvirus papio-2 infection in a black and white colobus
      monkey.
AB  - CASE DESCRIPTION: A 6.5-year-old female eastern black and white colobus monkey
      (Colobus guereza) was evaluated after acute onset of ataxia and inappetence.
      CLINICAL FINDINGS: The monkey was ataxic and lethargic, but no other
      abnormalities were detected via physical examination, radiography, or
      clinicopathologic analyses. During the next 2 days, the monkey's clinical
      condition deteriorated, and its WBC count decreased dramatically. Cytologic
      examination of a CSF sample revealed marked lymphohistiocytic inflammation.
      TREATMENT AND OUTCOME: Despite supportive care, the monkey became apneic; after
      20 hours of mechanical ventilation, fatal cardiac arrest occurred. At necropsy,
      numerous petechiae were detected within the white matter tracts of the brain;
      microscopic lesions of multifocal necrosis and hemorrhage with intranuclear
      inclusions identified in the brain and adrenal glands were consistent with an
      acute herpesvirus infection. A specific diagnosis of herpesvirus papio-2 (HVP-2)
      infection was made on the basis of results of serologic testing; PCR assay of
      tissue specimens; live virus isolation from the lungs; and immunohistochemical
      identification of the virus within brain, spinal cord, and adrenal gland lesions.
      Via phylogenetic tree analysis, the colobus HVP-2 isolate was grouped with
      neuroinvasive strains of the virus. The virus was most likely transmitted to the
      colobus monkey through toys shared with a nearby colony of baboons (the natural
      host of HVP-2). CLINICAL RELEVANCE: To the authors' knowledge, this is the first
      reported case of natural transmission of HVP-2 to a nonhost species. Infection
      with HVP-2 should be a differential diagnosis for acute encephalopathy in primate
      monkeys and humans, particularly following exposure to baboons.

PMID- 18081532
TI  - Recent advances in pig-to-human organ and cell transplantation.
AB  - Xenotransplantation using pigs offers the prospect of an unlimited number of
      organs and cells for clinical transplantation. A major step forward has been
      achieved with the introduction of pigs homozygous for alpha1,3
      galactosyltransferase gene-knockouts that do not express the major antigenic
      target for primate antipig antibodies (i.e., Galalpha1,3Gal). Heterotopic heart
      transplants have survived for 2-6 months in baboons. However, other immune and
      pathophysiologic barriers remain, including: i) anti-non-Gal antibodies and cells
      of the innate immune system; and ii) thrombogenesis associated with
      incompatibilities in the coagulation-anticoagulation systems of pig and primate.
      Further genetic modification of the organ-source pig to overcome these barriers
      is being undertaken.

PMID- 18081533
TI  - Rationale for anti-CD200 immunotherapy in B-CLL and other hematologic
      malignancies: new concepts in blocking immune suppression.
AB  - Immune evasion in cancer is increasingly recognized as a contributing factor in
      the failure of a natural host antitumor immune response as well as in the failure
      of cancer vaccine trials. Immune evasion may be the result of a number of
      factors, including expansion of regulatory T cells, production of
      immunosuppressive cytokines, downregulation of HLA class I and tumor-associated
      antigens and upregulation of immunosuppressive molecules on the surface of tumor
      cells. CD200, a cell surface ligand that plays a role in regulating the immune
      system, has been shown to be upregulated on the surface of some hematologic and
      solid tumor malignancies. This review characterizes the role of CD200 in immune
      suppression, and describes strategies to target this molecule in the oncology
      setting, thus directly modulating immune regulation and potentially altering
      tolerance to tumor antigens.

PMID- 18081534
TI  - Exploitation of stem cell homing for gene delivery.
AB  - Stem cells have been the focus of numerous investigations to treat diseases as
      far ranging as diabetes, chronic heart failure and multiple sclerosis over the
      past decade. The process of stem-cell-based repair of acute injury involves
      homing and engrafting of the stem cell of interest to the site of injury followed
      by either differentiation of the stem cell to indigenous end-organ cells or
      liberation of paracrine factors that lead to preservation and/or optimization of
      organ function. Recognition of the ability of stem cells to home to sites of
      acute injury suggests that, if appropriately defined and harnessed, stem cell
      homing could serve as a means of local drug delivery through the infusion of
      genetically engineering stem cells that secrete gene products of interest. The
      authors have recently demonstrated the use of this approach in preclinical
      studies of acute myocardial function. In addition, the use of engineered cells
      that home to appropriate niches have been used to correct genetic deficiency
      states (i.e., severe combined immunodeficiency, diabetes mellitus) in patients
      with otherwise chronic debilitating diseases. This review focuses on exploiting
      stem cell homing for gene transfer and on the state of the art and the challenges
      that face the field.

PMID- 18081535
TI  - Protective cancer immunotherapy: what can the innate immune system contribute?
AB  - Despite significant efforts to induce protection against malignant diseases, the
      clinical effects of antitumour vaccines are poor. However, recent studies on a
      quadrivalent human papilloma virus vaccine suggest that protection against
      secondary tumour development is feasible. While this scenario benefits rather
      from antiviral protection than from direct antitumour responses, immunisation
      against cancers of non-viral origin demands strategies that rely on the
      circumvention of intrinsic regulatory mechanisms. Strong activation of innate
      immune cells seems to be key and, thus, the choice of adjuvant determines
      vaccination efficacy. The recently acquired knowledge about molecular and
      cellular recognition of microbial molecules suggests how one can modulate innate
      and adaptive immune reactions to potentially induce robust T- and B-cell
      reactions capable of prohibiting tumour development and progression. Here, the
      authors review the present knowledge of innate immune reactions, which may help
      to define rationales on the design of novel antitumour vaccines.

PMID- 18081536
TI  - Galectin-1 as a potential therapeutic target in autoimmune disorders and cancer.
AB  - Galectin-1, a member of a family of highly conserved glycan-binding proteins, has
      emerged as a regulator of immune cell tolerance and homeostasis. This endogenous
      lectin widely expressed at sites of inflammation and tumour growth, has been
      postulated as an attractive immunosuppressive agent to restore immune cell
      tolerance and homeostasis in autoimmune and inflammatory settings. On the other
      hand, galectin-1 contributes to different steps of tumour progression including
      cell adhesion, migration and tumour-immune escape, suggesting that blockade of
      galectin-1 might result in therapeutic benefits in cancer. Recent findings
      implicating galectin-glycoprotein lattices as selective regulators of
      inflammatory responses have provided new insights into the understanding of the
      molecular bases of galectin-1-induced immunoregulation. Here the authors review
      the dual role of galectin-1 as a selective immunosuppressive agent in T helper
      (T(H))1 and T(H)17-mediated inflammatory/autoimmune disorders and a potential
      therapeutic target in cancer and metastasis.

PMID- 18081537
TI  - MicroRNAs as targets for antisense-based therapeutics.
AB  - MicroRNAs (miRNAs) are a novel class of endogenous non-coding single-stranded
      RNAs, which regulate gene expression post-transcriptionally by base pairing with
      their target mRNAs. So far > 5000 miRNA entries have been registered and miRNAs
      have been implicated in most, if not all, central cellular processes and several
      diseases. As the mechanism of action for miRNA regulation of target mRNAs is
      mediated by Watson-Crick base pairing, antisense oligonucleotides targeting the
      miRNAs appear as an obvious choice to specifically inhibit miRNA function.
      Indeed, miRNAs can be antagonized in vivo by oligonucleotides composed of high
      affinity nucleotide mimics. Lessons learned from traditional antisense strategies
      and small-interfering RNA approaches, that is from potent nucleotide mimics,
      design rules, pharmacokinetics, administration and safety issues, are likely to
      pave the way for future clinical trials of miRNA-antagonizing oligonucleotides.

PMID- 18081538
TI  - Neutrophils in antibody-based immunotherapy of cancer.
AB  - Monoclonal antibodies (mAb) are presently considered key therapeutic drugs for
      the treatment of malignancies. They can be designed to specifically target tumour
      associated antigens and initiate several effector mechanisms, which potentially
      leads to elimination of the tumour. Through their Fc tail mAbs interact with Fc
      receptors (FcR) that are expressed on immune cells. Neutrophils are the most
      abundant circulating FcR-expressing white blood cells with potent cytotoxic
      ability that is enhanced in the presence of antitumour mAbs. They furthermore
      play a role in regulating adaptive immunity, which may lead to the initiation of
      antitumour immune responses. Yet, neutrophils receive surprisingly little
      attention as potential effector cell population. This article reviews the
      scientific data that supports the possibility of exploiting neutrophils for mAb
      based immunotherapy of cancer. An increasing awareness and understanding of this
      topic may allow for future development of new anticancer therapies.

PMID- 18081539
TI  - Current use and development of vaccines for Japanese encephalitis.
AB  - BACKGROUND: Japanese encephalitis (JE) is a significant cause of human morbidity
      and mortality throughout Asia. Vaccines for JE have been available for many years
      and their use has been effective in reducing the incidence of JE disease in
      several countries but, as disease incidence has decreased, concerns regarding
      adverse events following immunisation have increased. OBJECTIVE: To review
      existing JE vaccines and new candidates in advanced preclinical or clinical
      evaluation. METHODS: The review primarily covers published and some unpublished
      literature from the past decade describing current use of approved JE vaccines in
      various parts of the world, and advanced development and clinical testing of
      alternative vaccine candidates. RESULTS/CONCLUSION: There is a clear need for
      additional licensing of existing or new JE vaccines. Several promising candidates
      are currently in use or completing clinical trials.

PMID- 18081540
TI  - Cetuximab in non-small cell lung cancer.
AB  - Advanced non-small cell lung carcinoma (NSCLC) remains a challenge to treat due
      to its high local and systemic recurrence. The overall survival remains poor
      despite the approval of several new chemotherapeutic agents in the management of
      advanced NSCLC. Overexpression or mutations in the EGFR have been shown to be
      associated with a significant percentage of NSCLC. The development of targeted
      agents, such as cetuximab, against the EGFR is therefore a rational objective.
      Several preclinical and clinical studies suggest that cetuximab is active against
      NSCLC. This paper reviews the application of cetuximab in NSCLC.

PMID- 18081541
TI  - Abatacept: the first T lymphocyte co-stimulation modulator, for the treatment of
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a multisystem autoimmune disease, of unknown
      aetiology with high morbidity and significantly increased mortality. Over recent
      years, the introduction of targeted therapies with biologic agents have made
      major inroads to the outcomes in RA. The first such agents developed were TNF
      alpha inhibitors. However, despite their high efficacy, up to 30% patients fail
      to respond adequately, or develop adverse reaction to TNF-alpha inhibitors. This
      suggests that other pathological mechanisms are involved, in addition to those
      mediated by TNF-alpha. Abnormal T-cell function has long been thought to play a
      key role in the pathogenesis of RA, stimulating both the production of pro
      inflammatory cytokines and recruitment of other inflammatory cells, resulting in
      joint destruction and systemic disease. Abatacept, the first of a group of T-cell
      co-stimulation modulators, targeting T-cell activation, has recently been
      licensed for use in RA and shows promise as a useful drug to treat this major
      disabling disease.

PMID- 18081542
TI  - Infliximab in dermatological treatment: beyond psoriasis.
AB  - Infliximab is a chimeric monoclonal antibody of the IgG1 class. Experience from
      its use has been accumulated in rheumatology and gastroenterology by the
      treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis
      and inflammatory bowel disease, respectively. Because of its TNF-alpha binding
      capacity it has been approved for the treatment of moderate-to-severe plaque
      psoriasis. Moreover, it has also been evaluated in other inflammatory dermatoses
      as well as systemic diseases involving the skin such as severe atopic dermatitis,
      pityriasis rubra pilaris, pyoderma gangrenosum and cutaneous sarcoidosis. The
      possible future uses of infliximab in dermatology are being reviewed herein.

PMID- 18081543
TI  - Hydroxylapatite-coated acetabular shells with arc deposited titanium surface
      roughening and dual radius design.
AB  - A retrospective review of two multicenter prospective stud- ies was performed of
      a dual radius design acetabular shell, one with a titanium arc deposited surface
      roughening and hydroxylapatite coating (AD HA) designed to optimize initial
      component stability and enhance biological ixation and the other grit-blasted and
      HA (GB HA) coated. The purpose of the study was to evaluate intermediate clinical
      and radiographic success of this device, as compared to a grit-blasted HA (GB HA)
      coated shell of the same design. Eighty-nine hips (83 patients) with a diagnosis
      of noninlam- matory degenerative joint disease (NIDJD) were implanted with the AD
      HA shells (Group 1) by three surgeons at three sites. Patients were evaluated
      clinically and radiographi- cally for 5 to 8 years postoperatively (mean, 5.5
      years). Clinical and radiographic data for 179 cases with GB HA shells and a
      diagnosis of NIDJD (Group 2) were reviewed retrospectively at an equivalent time
      frame. Fifty-eight hips in each group with a minimum 5-year follow-up were
      identiied through patient matching, based on age, gender, and preoperative body
      mass index, to provide the cohorts for this study. Radiographically, all patients
      in Group 1 were stable, and there were no cases of acetabular loosening or
      revision of the acetabular shell. Three patients in Group 2 had radiographic
      evidence of acetabular shell migration and eight shells (three dislocations, ive
      acetabular loosenings) had been revised by 60 months postoperatively.
      Intermediate results with the AD HA shells are encouraging, as evidenced by
      clinical success, radiographic stability, and 100% survi- vorship at 5 to 8 years
      (mean, 66 months).

PMID- 18081544
TI  - Acetabular development in developmental dysplasia of the hip. A radiographic
      study in anatomically reduced and uncomplicated hips.
AB  - The objective of this prospective, controlled study was to assess the
      radiographic course of acetabular develop- ment in developmental dysplasia of the
      hip (DDH). The study consisted of 14 patients (mean age at operation, 12 months;
      range, 6 to 18 months) from a large, prospective series diagnosed with unilateral
      DDH and treated by a soft tissue surgical procedure via the posteromedial
      approach. All patients had intraoperative radiographic anatomic reductions, did
      not have any type of complica- tion during follow-up, and were followed until at
      least 10 years of age. Unaffected contralateral hips were used as controls. The
      acetabular angle of Sharp (AA) was measured to determine acetabular development.
      Mean follow-up was 112 months. A significant difference (p < 0.005) was observed
      between the mean AA values of affected and unaffected hips at operation and at
      the first three follow-up visits (mean age was 24, 41, and 56 months,
      respectively). This significant difference was not present (p > 0.05) at the
      latest two follow-up visits (mean age was 90 and 124 months, respectively). It
      can be concluded that a marked radiographic improvement in acetabular slope
      occurs within 1 year postoperatively. This improvement continues slowly during
      the childhood period, and the acetabulum attains previously determined normal AA
      values at nearly 7 to 8 years of age for those patients whose dysplastic hips
      were anatomically reduced at less than 18 months of age and for those who did not
      experience complications during follow-up.

PMID- 18081545
TI  - Fracture-dislocation of the elbow functional outcome following treatment with a
      standardized protocol.
AB  - Fracture-dislocation of the elbow is a signiicant injury with mixed outcomes. The
      purpose of the study was to evaluate patient perceived outcome following surgical
      stabilization of these complex injuries. Twenty-nine available patients (76%)
      from 37 identiied with "terrible triad" injury patterns, in- cluding ulnohumeral
      dislocation, radial head fracture, and coronoid fracture, were available for a
      minimum 1-year follow-up (mean, 27 months). All patients were evaluated by their
      treating physician. Radiographic outcome was evaluated at latest follow-up.
      Functional outcome was based upon DASH, Mayo elbow performance, and Broberg-Mor-
      rey scores. Complications were recorded. Results included that the average lexion
      extension arc of elbow motion was 109 degrees +/- 27 degrees , and the average
      pronation-supination arc was 128 degrees +/- 44 degrees . Grip strength averaged
      72% of the contralateral extremity. The Mayo score was a mean of 81 (range, 45 to
      100), the Broberg-Morrey mean was 77 (range, 33 to 100) The mean DASH was 28
      (range, 0 to 72). When compared to the age-based normal values, the mean
      patient's DASH score was 1.4 SD worse than an average person of the same age None
      of the injury characteristics, patient demographics or treatment modalities was
      signiicantly associated with a poor outcome at the 95% conidence interval.
      Conclusions are that the results with terrible triad injuries are often
      unsatisfactory, but surgical management with the use of a systematic approach may
      be beneicial. Our approach led to the restoration of elbow joint stability in all
      patients.

PMID- 18081546
TI  - Patella instability.

PMID- 18081547
TI  - Comparison of fixation methods for scaphoid nonunions: a biomechanical model.
AB  - The purpose of this study was to analyze the relative bio- mechanical stability
      of three types of internal ixation with cancellous bone graft in a cadaveric,
      scaphoid nonunion model. A scaphoid nonunion model was created by remov- ing a
      volar wedge of bone from the waist of the scaphoid in 18 fresh frozen human
      cadavers. Cancellous sawbone graft was inserted into the osteotomy site and three
      groups of six cadavers each were then internally ixed with a pair of parallel
      0.045-inch K-wires, Mini-Acutrak screws, or Standard Acutrak screws, respectively
      for each group. The potted specimens were tested using an Instron(R) tensile
      testing machine by applying force to the distal pole of the scaphoid. The load
      and stiffness were calculated at 2 mm and 4 mm of displacement. Results showed
      that both the Mini-Acutrak screw and the Standard Acutrak screw were
      statistically stronger and stiffer at 2 mm displacement than the pair of parallel
      0.045-inch K-wires. No statistically sig- niicant difference between the Standard
      and Mini-Acutrak screws was noted at 2 mm displacement. At higher loads (4 mm
      displacement), the Standard Acutrak became statisti- cally stronger and stiffer
      than the Mini-Acutrak screw. It was concluded that the Standard Acutrak screw
      followed by the Mini-Acutrak screw may be a better option than a pair of parallel
      0.045-inch K-wires when treating scaphoid nonunions. The screws have increased
      strength of ixation and stiffness when compared to K-wires. Also, unlike the K
      wires, the Acutrak screws enhance fracture healing by achieving interfragmentary
      compression. Even in a cancel- lous bone graft model, interfragmentary
      compression was achieved and our concern that the bone graft would "spit out" was
      allayed.

PMID- 18081548
TI  - Biomechanics of external fixation: a review of the literature.
AB  - External fixation for the purpose of bony realignment has been in practice since
      the early 1900s and is widely used today. External fixators are primarily used
      for trauma but may also be used for deformity correction and arthrodesis, among
      other applications. The advantages of external fixation over open reduction and
      internal fixation and intramedullary nailing include simplicity of application,
      adjustability of the construct, and increased access for wound care and wound
      monitoring after fixation is achieved. Frame design requires a combination of
      pins, wires, clamps, rings, and rods to ultimately form a stable construct that
      can apply compressive, distractive, or neutral forces on bone.

PMID- 18081549
TI  - Rheumatoid arthritis treatment and monitoring of outcomes--where are we
      [corrected] in 2007?
AB  - Rheumatoid arthritis (RA) treatment has witnessed major advances over the last 10
      to 20 years. Methotrexate has emerged as the cornerstone of treatment with new
      biologic agents being used in addition in severe and resistant patients. New
      drugs being developed with novel modes of action are promising to expand
      treatment options and help provide better disease control for RA patients. In
      addition to medications, equally important is aggressive disease activity
      monitoring using one of the composite scores available in order to match
      treatments to disease activity. Disease activity score (DAS), DAS28 (with a 28
      joint count), clinical disease activity index (CDAI), simplified disease activity
      index (SDAI), and routine assessment of patient index data (RAPID) are valuable
      tools and should be used in routine care to achieve disease control.

PMID- 18081550
TI  - The modified racking hitch(MRH) knot: a new sliding knot for arthroscopic
      surgery.
AB  - Sliding knots are commonly used in arthroscopic surgery and can be problematic in
      terms of strength and loop security. A new sliding knot for arthroscopic surgery,
      a modified racking hitch (MRH) knot, is described. The knot is essentially a
      modified cow's hitch knot that includes two self-locking loops. By tensioning the
      loop strands, a snug knot is created without backward sliding and provides
      excellent knot and loop security. In laboratory testing, the MRH knot provided
      comparable strength and security to other sliding knots. Experience gained from
      approximately 5 years of clinical use has added to the promise of the useful
      application of the MRH knot in arthroscopy.

PMID- 18081551
TI  - Septic arthritis of the acromioclavicular joint - a report of four cases.

PMID- 18081552
TI  - Surgical management of os acromiale: a case report and review of the literature.

PMID- 18081554
TI  - Isolation and characterisation of four cDNAs encoding neuromedin U (NMU) from the
      brain and gut of goldfish, and the inhibitory effect of a deduced NMU on food
      intake and locomotor activity.
AB  - In rodents, neuromedin U (NMU; U for its original effects examined in the uterus)
      is a multifunctional neuropeptide implicated in the regulation of the circulatory
      and digestive systems and energy homeostasis, especially appetite. However, there
      is no available information on the nature and physiological roles of NMU in fish.
      Therefore, we attempted to isolate and characterise transcripts encoding NMU from
      the brain and gut of the goldfish, and to examine the involvement of NMU in the
      regulation of feeding behaviour in this species. We identified four cDNAs
      encoding three NMU orthologs from the brain and gut. Putative peptides consisting
      of 21, 25 and 38 amino acid residues (NMU-21, NMU-25 and NMU-38) were deduced
      from their nucleotide sequences. Two mRNAs for NMU-25 were strongly expressed in
      the gut and weakly expressed in the brain and testis. By contrast, mRNA for NMU
      21 was strongly expressed in the brain and weakly expressed in the peripheral
      tissues. Expression of mRNA for NMU-38 was weakly expressed only in the brain.
      Therefore, we examined the effect of feeding status on the expression of NMU-21
      mRNA in the brain. Fasting for 7 days induced a significant decrease in the
      expression levels of NMU-21 mRNA in the brain. We also synthesised NMU-21 after
      deducing its C-terminal amide from the NMU-21 mRNA, and then investigated the
      effect of intracerebroventricular (i.c.v.) administration of NMU-21 on food
      intake and locomotor activity in the goldfish. NMU-21, injected i.c.v.,
      suppressed food intake and locomotor activity in a dose-dependent manner. These
      results suggest that NMU orthologs exist in fish, and that the NMU-21 deduced
      from them can potently inhibit food intake and locomotor activity in goldfish.

PMID- 18081555
TI  - Chronic central administration of apelin-13 over 10 days increases food intake,
      body weight, locomotor activity and body temperature in C57BL/6 mice.
AB  - The peptide apelin has been located in a wide range of tissues, including the
      gastrointestinal tract, stomach and adipose tissue. Apelin and its receptor has
      also been detected in the arcuate and paraventricular nuclei of the hypothalamus,
      which are involved in the control of feeding behaviour and energy expenditure.
      This distribution suggests apelin may play a role in energy homeostasis, but
      previous attempts to discern the effects of apelin by acute injection into the
      brain have yielded conflicting results. We examined the effect of a chronic 10
      day intracerebroventricular (i.c.v.) infusion of apelin-13 into the third
      ventricle on food intake, body temperature and locomotor activity in C57BL/6
      mice. Apelin-13 (1 microg/day) increased food intake significantly on days 3-7 of
      infusion; thereafter, food intake of treated and control individuals converged.
      This convergence was potentially because of progressive conversion of apelin-13
      to [Pyr(1)]apelin-13 which has a four-fold lower receptor binding affinity at the
      orphan G protein-coupled receptor, APJ. Locomotor activity was also higher in the
      apelin-treated mice, especially during the nocturnal peak, when most feeding
      occurs, and the first hours of the light phase. Body temperature was also
      elevated during this increased period of activity, but was otherwise unaffected.
      Apelin-13-infused animals gained more weight than the saline-infused controls,
      suggesting the elevated locomotor activity did not offset the increased food
      intake. Elevated locomotion and the consequent increases in body temperature were
      probably secondary effects to the increased food intake. These results suggest
      that apelin-13 may play a central role in the control of feeding behaviour and is
      one of only two peripheral ligands known to stimulate rather than inhibit intake.
      As apelin production is elevated during obesity, this may provide an important
      feed-forward mechanism exacerbating the problem. Antagonists of the apelin
      receptor may therefore be useful pharmaceuticals in the treatment of obesity.

PMID- 18081556
TI  - The anti-ghrelin Spiegelmer NOX-B11-3 blocks ghrelin- but not fasting-induced
      neuronal activation in the hypothalamic arcuate nucleus.
AB  - The hypothalamic arcuate nucleus (Arc) is the presumed target site for the
      orexigenic hormone ghrelin, which is secreted from the stomach during fasting.
      Ghrelin directly activates Arc neurones. Similar to exogenous ghrelin, overnight
      food deprivation also induces c-Fos expression in the Arc of mice. In the present
      study, we tested the role of endogenous ghrelin in the fasting-induced c-Fos
      expression in the Arc of mice. We used NOX-B11-3, the latest generation of the
      recently developed ghrelin-binding compounds, so-called RNA Spiegelmers (SPM) to
      block endogenous ghrelin action during food deprivation. The specificity and
      potency of this compound was also tested in electrophysiological and
      immunohistological experiments. In electrophysiological in vitro single cell
      recordings, NOX-B11-3 effectively blocked the excitatory effect of ghrelin in the
      medial Arc (ArcM) of rats whereas the biologically inactive control SPM had no
      effect. Furthermore, NOX-B11-3 (15 mg/kg i.p.) potently suppressed ghrelin
      induced (25 microg/kg s.c., 12 h after SPM injection) c-Fos expression in the
      Arc. However, when injected at the beginning of a 14-h fasting period, the same
      dose of NOX-B11-3 had no effect on the c-Fos expression in the Arc of mice. These
      results demonstrate that NOX-B11-3 is a long-acting compound, which effectively
      blocks the effect of exogenous ghrelin on neuronal activity in the Arc under in
      vitro and in vivo conditions. Furthermore, increased ghrelin signalling does not
      appear to be a necessary factor for the activation of Arc neurones during food
      deprivation or other fasting-related signals might have masked or compensated for
      the loss of the ghrelin effect.

PMID- 18081557
TI  - Temporal migration of gonadotrophin-releasing hormone-1 neurones is modified in
      GAD67 knockout mice.
AB  - Gonadotrophin-releasing hormone (GnRH-1) neurones reside in the forebrain and
      regulate gonadal function via the hypothalamic-pituitary-gonadal axis. Disruption
      of this axis results in reproductive dysfunction. During embryonic development,
      GnRH-1 neurones migrate from the nasal pit through the nasal/forebrain junction
      (NFJ) into the developing brain. Prenatally gamma-aminobutyric acid (GABA) is
      excitatory and has been shown to play a role in nervous system development. Both
      in vivo and in vitro experiments suggest that GABA inhibits migration of GnRH-1
      neurones. The present study examines the migration of GnRH-1 neurones in GAD67
      knockout (KO) mice to further elucidate the role of GABA on GnRH-1 neuronal
      development. Three stages were examined, embryonic day (E)12.5, E14.5 and E17.5.
      GnRH-1 cell number and location were analysed by immunocytochemistry and in situ
      hybridisation histochemistry. The total number of GnRH-1 immunopositive cells was
      similar between wild-type (WT) and KO mice. However, significant differences were
      found in the overall distribution of GnRH-1 immunopositive cells in GAD67 KO
      compared to WT mice at all stages. Subsequent analysis by area revealed
      differences occurred at the NFJ with an increase in GnRH-1 cells in GAD67 KO at
      E14.5 and a decrease in GnRH-1 cells in GAD67 KO at E17.5. Comparable counts for
      cells expressing GnRH-1 transcript and protein were obtained. These data indicate
      that attenuated levels of GABA accelerate GnRH-1 cell migration in nasal areas as
      well as movement of GnRH-1 cells into the central nervous system at the NFJ.

PMID- 18081558
TI  - Pituitary function and the somatotrophic system in patients with idiopathic
      Parkinson's disease under chronic dopaminergic therapy.
AB  - Idiopathic Parkinson's disease and dopaminergic medication may influence
      pituitary hormone secretion. The present study aimed to reveal any abnormalities
      of the somatotrophic system induced by the disease itself and/or the dopaminergic
      therapy. Investigations of other pituitary hormones under basal and stimulated
      conditions, as well as an analysis of body composition, were also performed. This
      was a controlled diagnostic study in which luteinising hormone-releasing hormone,
      thyroid-releasing hormone, corticotrophin-releasing hormone and arginine
      hydrochloride were administered to ten patients with idiopathic Parkinson's
      disease under dopaminergic medication. Basal and stimulated hormone
      concentrations and bioelectrical impedance analyses were compared with those of
      healthy, age-matched controls. Basal growth hormone (GH) at -30 and 0 min was
      higher in Parkinsonian patients (2.74 +/- 3.79 ng/ml versus 0.53 +/- 0.10 ng/ml
      and 2.12 +/- 2.44 ng/ml versus 0.51 +/- 0.03 ng/ml; P < 0.05). The area under the
      GH curve after stimulation was greater in Parkinsonian patients (502.4 +/- 202.6
      ng x min/ml versus 312.0 +/- 98.5 ng x min/ml; P < 0.05), depending on higher
      basal GH levels, rather than a greater arginine response. No differences in
      insulin growth factor (IGF)-1 or IGF-BP3 concentrations were detected. There were
      no differences between the groups in basal and stimulated gonadotrophic,
      corticotrophic and thyrotrophic function, or body composition. Prolactin was
      below the detection limit in the patients during the course of the study.
      Parkinsonian patients experience marked hypoprolactinaemia and repeated
      stimulation of GH secretion during chronic dopaminergic therapy. Our findings
      suggest a peripheral GH resistance in these chronically-treated patients.

PMID- 18081559
TI  - Alpha-oestrogen and progestin receptor expression in the hypothalamus and
      preoptic area dopaminergic neurones during oestrous in cycling rats.
AB  - A secretory surge of prolactin occurs on the afternoon of oestrous in cycling
      rats. Although prolactin is regulated by ovarian steroids, plasma oestradiol and
      progesterone levels do not vary during oestrous. Because prolactin release is
      tonically inhibited by hypothalamic dopamine and modulated by dopamine
      transmission in the preoptic area (POA), the present study aimed to evaluate
      whether oestrogen receptor (ER)-alpha and progestin receptor (PR) expression in
      the dopaminergic neurones of arcuate (ARC), periventricular, anteroventral
      periventricular (AVPe) and ventromedial preoptic (VMPO) nuclei changes during the
      day of oestrous. Cycling rats were perfused every 2 h from 10-20 h on oestrous.
      Brain sections were double-labelled to ERalpha or PR and tyrosine hydroxylase
      (TH). The number of TH-immunoreactive (ir) neurones did not vary significantly in
      any area evaluated. ERalpha expression in TH-ir neurones increased at 14 and 16 h
      in the rostral-ARC and dorsomedial-ARC, 14 h in the caudal-ARC and 16 h in the
      VMPO, whereas it was unaltered in the ventrolateral-ARC, periventricular and
      AVPe. PR expression in TH-ir neurones of the periventricular and rostral,
      dorsomedial, ventrolateral and caudal-ARC decreased transitorily during the
      afternoon, showing the lowest levels between 14 and 16 h; but it did not vary in
      the AVPe and VMPO. Plasma oestradiol and progesterone concentrations were low and
      unaltered during oestrous, indicating that the changes in receptors expression
      were probably not due to variation in ligand levels. Thus, our data suggest that
      variations in ERalpha and PR expression may promote changes in the activity of
      medial basal hypothalamus and POA dopaminergic neurones, even under unaltered
      secretion of ovarian steroids, which could facilitate the occurrence and modulate
      the magnitude of the prolactin surge on oestrous.

PMID- 18081560
TI  - Leptin deficiency per se dictates body composition and insulin action in ob/ob
      mice.
AB  - Obese humans are often insulin- and leptin resistant. Since leptin can affect
      glucose metabolism, it is conceivable that a lack of leptin signal transduction
      contributes to insulin resistance. It remains unclear whether leptin affects
      glucose metabolism via peripheral and/or central mechanistic routes. In the
      present study, we aimed: (i) to determine the relative contributions of lack of
      leptin signal transduction and adiposity to insulin resistance and (ii) to
      establish the impact of central leptin action on glucose metabolism. To address
      the first point, ob/ob mice were subjected to severe calorie restriction, so that
      their body weight became similar to that of wild-type mice. Insulin sensitivity
      was measured in obese ob/ob, lean (food restricted) ob/ob and lean, weight
      matched wild-type mice. To address the second point, leptin (or vehicle) was
      i.c.v. infused to the lateral cerebral ventricle of ob/ob mice and insulin
      sensitivity was determined. Hyperinsulinaemic euglyceamic clamps were used to
      quantify insulin sensitivity. Food restriction barely affected body composition,
      although it profoundly curtailed body weight. Insulin suppressed hepatic glucose
      production (HGP) to a greater extent in lean ob/ob than in obese ob/ob mice, but
      its impact remained considerably less than in wild-type mice (% suppression: 11.8
      +/- 8.9 versus 1.3 +/- 1.1 versus 56.6 +/- 13.0%/nmol, for lean, obese ob/ob and
      wild-type mice, respectively; P < 0.05). The insulin-mediated glucose disposal
      (GD) of lean ob/ob mice was also in between that of obese ob/ob and wild-type
      mice (37.5 +/- 21.4 versus 25.1 +/- 14.6 versus 59.6 +/- 17.3 mumol/min/kg/nmol
      of insulin, respectively; P < 0.05 wild-type versus obese ob/ob mice). Leptin
      infusion acutely enhanced both hepatic insulin sensitivity (insulin-induced
      inhibition of HGP) and insulin-mediated GD (9.1 +/- 2.4 versus 5.0 +/- 2.7%/nmol
      of insulin, and 25.6 +/- 5.6 versus 13.6 +/- 4.8 mumol/min/kg/nmol of insulin,
      respectively; P < 0.05 for both comparisons) in ob/ob mice. Both a lack of leptin
      signals and adiposity may contribute to insulin resistance in obese individuals.
      Diminution of central leptin signalling can critically affect glucose metabolism
      in these individuals.

PMID- 18081562
TI  - Stem cells, hormones and pituitary adenomas.
AB  - We still do not understand the pathogenesis of the majority of pituitary adenomas
      or why, once formed, their behaviour tends to be so benign. Understanding trophic
      activity in the normal pituitary may be the key. Despite the fact that changes in
      indices of cell division and programmed cell death that are too small to measure
      can produce highly significant fluxes in cell populations, little by little, the
      fascinating patterns of integrated responses of pituitary cells to hormonal
      stimuli are now being revealed.

PMID- 18081561
TI  - The effects of galanin-like peptide on energy balance, body temperature and brain
      activity in the mouse and rat are independent of the GALR2/3 receptor.
AB  - Galanin-like peptide (GALP) is a neuropeptide that is thought to act on the
      galanin receptors GALR1, GALR2 and GALR3. In rats, i.c.v. injection of GALP has
      dichotomous actions on energy balance, stimulating feeding over the first hour,
      but reducing food intake and body weight at 24 h, as well as causing an increase
      in core body temperature. In mice, GALP only induces an anorexic action, and its
      effects on core body temperature are unknown. One aim of the present study was to
      determine the effects of GALP on core body temperature in mice.
      Intracerebroventricular injection of GALP into conscious mice had no effect on
      feeding over 1 h, but caused a significant reduction in food intake and body
      weight at 24 h. It also caused an immediate drop in core body temperature, which
      was followed by an increase in body temperature. To understand these different
      effects of GALP on energy balance in mice compared to rats, and to determine the
      involvement of GALR2 and GALR3, immunohistochemistry was performed to localise c
      Fos, a marker of cell activation. Intracerebroventricular injection of GALP
      induced c-Fos expression in the parenchyma surrounding the ventricles, the
      ventricular ependymal cells and the meninges in mice and rats. GALP also induced
      c-Fos expression in the supraoptic nucleus, dorsomedial hypothalamic nucleus,
      lateral hypothalamus and nucleus tractus solitarius in rats but not in mice.
      Central administration of a GALR2/3 agonist in rats did not induce c-Fos in any
      of the brain regions that expressed this protein after GALP injection, and had no
      effect on food intake, body weight and body temperature in rats or mice. These
      data suggest that GALP induces differential effects on energy balance and brain
      activity in mice compared to rats, which are unlikely to be due to activation of
      the GALR2 or GALR3 receptor.

PMID- 18081563
TI  - BSACI guidelines for the management of allergic and non-allergic rhinitis.
AB  - This guidance for the management of patients with allergic and non-allergic
      rhinitis has been prepared by the Standards of Care Committee (SOCC) of the
      British Society for Allergy and Clinical Immunology (BSACI). The guideline is
      based on evidence as well as on expert opinion and is for use by both adult
      physicians and paediatricians practicing in allergy. The recommendations are
      evidence graded. During the development of these guidelines, all BSACI members
      were included in the consultation process using a web-based system. Their
      comments and suggestions were carefully considered by the SOCC. Where evidence
      was lacking, consensus was reached by the experts on the committee. Included in
      this guideline are clinical classification of rhinitis, aetiology, diagnosis,
      investigations and management including subcutaneous and sublingual
      immunotherapy. There are also special sections for children, co-morbid
      associations and pregnancy. Finally, we have made recommendations for potential
      areas of future research.

PMID- 18081565
TI  - The central role of reviewers in sustaining this journal.

PMID- 18081566
TI  - The scope, mission and method of contemporary public health.
AB  - A coherent public health response is critical to successfully addressing a wide
      range of issues facing society - from avian influenza through to climate change
      and obesity. Much can be learned from the long and varied history of public
      health. From the pioneering work of Ibn Sina to the 'new public health' and
      recent WHO commission on the social determinants of health, we see that public
      health has been constantly responsive to emerging concerns. It is also clear that
      it is not only 'traditional' notions of public health but action from diverse
      fields has helped to achieve the improvements in health that we now see. However,
      great inequality in health outcomes remain as we enter the 21st Century. Our
      challenge as the public health community is to engage diverse groups in
      advocating not just for health, but also for reductions in poverty and
      inequality.

PMID- 18081567
TI  - How can public health deal with the problems set by neo-liberalism? A response to
      'The scope, mission and method of contemporary public health'.

PMID- 18081568
TI  - Clients' perspective on service quality for type 2 diabetes in Australia.
AB  - OBJECTIVES: To explore the needs, expectations, feelings and experiences of
      people with type 2 diabetes for developing quantitative instruments for a
      questionnaire study of service quality. METHODS: Using two focus group
      discussions (n=33), potential service quality dimensions for type 2 diabetes were
      assessed for Australian relevance. These included 11 indicators identified from a
      systematic literature review: communication, autonomy, choice of care provider,
      continuity of care, quality of basic amenities, dignity, timeliness, prevention
      and early detection, safety, confidentiality and availability. RESULTS: The focus
      group discussions supported the importance of the 11 service quality indicators
      but gave more importance to education, diet, communication, autonomy, choice of
      care provider and support group and less to confidentiality and availability.
      Three new themes were generated from the discussions: education, diet and support
      group. CONCLUSION: Measuring service quality for type 2 diabetes requires
      considering health system, culture and disease-specific factors.

PMID- 18081569
TI  - Analysis of primary prevention services for cardiovascular disease in Australia's
      community pharmacies.
AB  - OBJECTIVE: To analyse the prevalence and factors associated with the provision of
      primary preventive services for cardiovascular disease (CVD) in Australia's
      community pharmacies. METHODS: The data were from the 2002 Australia's National
      Pharmacy Database Project. Questionnaires were completed by a nationally
      representative 1,131 out of a possible 1,391 pharmacies (81.3% response rate),
      stratified into PhARIA (remoteness) zones. Preventive services for CVD were
      analysed by frequency of provision of services. Ordinal analysis and logistic
      regression analysis were used to ascertain predictors of services. RESULTS: Most
      community pharmacies initiated nicotine replacement therapies, 58.1% provided
      blood pressure screening, 11.6% anthropometric tests and 7.6% blood cholesterol
      screening. Pharmacies in promotional groups, having high customer numbers, an
      enclosed counselling area, or forward pharmacy area, were significantly
      associated with providing preventive services for CVD. CONCLUSIONS AND
      IMPLICATION: The configuration and size of Australia's community pharmacies were
      associated with providing primary preventive services for CVD.

PMID- 18081570
TI  - Stroke surveillance: population-based estimates and projections for New Zealand.
AB  - OBJECTIVE: To estimate the incidence, prevalence and mortality of stroke in New
      Zealand (NZ) in 2001, projected to 2011. METHODS: Multistate lifetable models
      were constructed using smoothed rates of first-ever stroke incidence and relative
      risks of mortality estimated from the most recent Auckland Regional Community
      Stroke (ARCOS) Study. Estimates of the burden of stroke in NZ were calculated by
      applying rates output by the model to the 2001 population. Stroke incidence,
      prevalence and mortality were then projected to 2011, assuming similar trends in
      stroke incidence and case fatality to those estimated between the 1991/92 and
      2002/03 studies. RESULTS: A total of 5,200 first-ever strokes were estimated to
      have occurred in NZ in 2001. Rates of stroke rose exponentially with increasing
      age and were 20% higher among males than females at most ages. Nevertheless, the
      lifetable risk of stroke was lower for males (16%) than females (18%). On
      average, males survived a year longer than females after a first-ever stroke (9.0
      vs. 8.2 years). The incidence rates of first-ever stroke declined by
      approximately 1% per year between 1991 and 2003. The lifetable risk of stroke
      remained stable for females but increased for males (from 14% to 16%) over this
      period. Stroke prevalence also increased by approximately 1% per year, whereas
      stroke-related mortality fell by 4% per year. If these trends continue,
      approximately 6,000 first-ever strokes (2% annual increase), 45,000 stroke
      survivors (2% annual increase) and 2,000 stroke-related deaths (1% annual
      decline) are expected in 2011. CONCLUSION: Stroke mortality is falling faster
      than stroke incidence. This, together with population growth and ageing, will
      lead to a rising burden of stroke-related disability over the next decade.

PMID- 18081571
TI  - Safe storage of methadone takeaway doses - a survey of patient practice.
AB  - OBJECTIVE: To determine current methadone takeaway storage practice among
      patients receiving supervised methadone treatment and takeaway doses at community
      pharmacies. METHODS: A cross-sectional survey was conducted in 2006 in Sydney,
      New South Wales. It addressed: safe storage of methadone takeaways; knowledge of
      risk of methadone ingestion by small children; and information provision from
      health care providers about the safe storage of methadone. RESULTS: Eighty-seven
      patients participated in the survey. The majority stored their methadone
      takeaways in a cupboard (48%) or secure cabinet (34%). All but one participant
      were aware of the risks of methadone ingestion by small children. Eighty-seven
      per cent had discussed safe storage of takeaways with a health professional.
      CONCLUSIONS: Most patients receiving methadone takeaways store them safely and
      are aware of the risk that methadone ingestion poses to children. IMPLICATIONS:
      Clinicians should ensure patients are adequately informed about safe takeaway
      storage and the risk of methadone ingestion by children.

PMID- 18081572
TI  - The use of alcohol and medicines among Australian adults.
AB  - OBJECTIVE: To collect Australian population-based data on concurrent use of
      conventional medicines, complementary/alternative medicines (CAM), and alcohol.
      METHOD: National survey administered in December 2005 to 816 Australian adults.
      RESULTS: 71% of respondents reported recent (last 24 hour) use of conventional
      medicine or CAM. 24% had recently consumed alcohol and conventional medicine, 17%
      alcohol and CAM and 13% alcohol and both types of medicines. Use of blood
      pressure and arthritis medicines was significantly more likely among daily
      drinkers than less than daily drinkers and non-drinkers. CONCLUSIONS: Concurrent
      use of medicines and alcohol is common, particularly among older people.
      IMPLICATIONS: Use of alcohol may have an impact on the stability of chronic
      illness managed by medicines or other types of interactions with medicines, such
      as sedation. Health care professionals should routinely inquire about such use to
      be able to incorporate appropriate safety strategies into clinical management.

PMID- 18081573
TI  - Prescribed stimulant use by Western Australians with Attention Deficit
      Hyperactivity Disorder (ADHD): does amount dispensed exceed the expected
      authorised use?
AB  - OBJECTIVE: To investigate to what extent Western Australian (WA) patients with
      Attention Deficit Hyperactivity Disorder (ADHD) received prescribed stimulants in
      excess of their notified dose from WA pharmacies in 2004 (termed 'discrepancy').
      DESIGN AND DATA SOURCES: Analysis of administrative data about all people aged
      two years and older who were prescribed stimulants for the treatment of ADHD in
      WA, and had at least one stimulant prescription dispensed from a WA pharmacy
      during the period 1 January to 31 December 2004. OUTCOME MEASURES: Discrepancies
      were identified using minimum and maximum estimation methods (MinDE, MaxDE). We
      calculated for both methods the discrepancy prevalence by age and sex and annual
      surplus of stimulant accrued by age. RESULTS: Of the 15,190 ADHD patients who
      comprised the study population, 5.4% to 19.0% received stimulants surplus to
      requirement in 2004, with peak prevalences in 6-8 year-olds (MaxDE 20.1%) and 25
      34 year-olds (MaxDE 27.6%; MinDE 10.5%). The amount of stimulant dispensed
      surplus to requirement was highly skewed, with median annual values that ranged
      from one to 4.1 standard bottles (100 tablets) of dexamphetamine 5 mg for the
      MinDE and MaxDE methods, respectively. CONCLUSION: It is difficult to
      definitively estimate to what extent WA ADHD patients accrued excess stimulant
      medication using routine administrative data. Improvements to the WA Stimulant
      Regulatory Guidelines are recommended in the interests of patient safety, public
      transparency, methodological rigour and encouraging good prescribing practices.

PMID- 18081574
TI  - What have sampling and data collection got to do with good qualitative research?
AB  - OBJECTIVE: To highlight the importance of sampling and data collection processes
      in qualitative interview studies, and to discuss the contribution of these
      processes to determining the strength of the evidence generated and thereby to
      decisions for public health practice and policy. APPROACH: This discussion is
      informed by a hierarchy-of-evidence-for-practice model. The paper provides
      succinct guidelines for key sampling and data collection considerations in
      qualitative research involving interview studies. The importance of allowing time
      for immersion in a given community to become familiar with the context and
      population is discussed, as well as the practical constraints that sometimes
      operate against this stage. The role of theory in guiding sample selection is
      discussed both in terms of identifying likely sources of rich data and in
      understanding the issues emerging from the data. It is noted that sampling
      further assists in confirming the developing evidence and also illuminates data
      that does not seem to fit. The importance of reporting sampling and data
      collection processes is highlighted clearly to enable others to assess both the
      strength of the evidence and the broader applications of the findings.
      CONCLUSION: Sampling and data collection processes are critical to determining
      the quality of a study and the generalisability of the findings. We argue that
      these processes should operate within the parameters of the research goal, be
      guided by emerging theoretical considerations, cover a range of relevant
      participant perspectives, and be clearly outlined in research reports with an
      explanation of any research limitations.

PMID- 18081575
TI  - Generating best evidence from qualitative research: the role of data analysis.
AB  - OBJECTIVE: To outline the importance of the clarity of data analysis in the doing
      and reporting of interview-based qualitative research. APPROACH: We explore the
      clear links between data analysis and evidence. We argue that transparency in the
      data analysis process is integral to determining the evidence that is generated.
      Data analysis must occur concurrently with data collection and comprises an
      ongoing process of 'testing the fit' between the data collected and analysis. We
      discuss four steps in the process of thematic data analysis: immersion, coding,
      categorising and generation of themes. CONCLUSION: Rigorous and systematic
      analysis of qualitative data is integral to the production of high-quality
      research. Studies that give an explicit account of the data analysis process
      provide insights into how conclusions are reached while studies that explain
      themes anchored to data and theory produce the strongest evidence.

PMID- 18081553
TI  - Paracrinicity: the story of 30 years of cellular pituitary crosstalk.
AB  - Living organisms represent, in essence, dynamic interactions of high complexity
      between membrane-separated compartments that cannot exist on their own, but reach
      behaviour in co-ordination. In multicellular organisms, there must be
      communication and co-ordination between individual cells and cell groups to
      achieve appropriate behaviour of the system. Depending on the mode of signal
      transportation and the target, intercellular communication is neuronal, hormonal,
      paracrine or juxtacrine. Cell signalling can also be self-targeting or autocrine.
      Although the notion of paracrine and autocrine signalling was already suggested
      more than 100 years ago, it is only during the last 30 years that these
      mechanisms have been characterised. In the anterior pituitary, paracrine
      communication and autocrine loops that operate during fetal and postnatal
      development in mammals and lower vertebrates have been shown in all hormonal cell
      types and in folliculo-stellate cells. More than 100 compounds have been
      identified that have, or may have, paracrine or autocrine actions. They include
      the neurotransmitters acetylcholine and gamma-aminobutyric acid, peptides such as
      vasoactive intestinal peptide, galanin, endothelins, calcitonin, neuromedin B and
      melanocortins, growth factors of the epidermal growth factor, fibroblast growth
      factor, nerve growth factor and transforming growth factor-beta families,
      cytokines, tissue factors such as annexin-1 and follistatin, hormones, nitric
      oxide, purines, retinoids and fatty acid derivatives. In addition, connective
      tissue cells, endothelial cells and vascular pericytes may influence
      paracrinicity by delivering growth factors, cytokines, heparan sulphate
      proteoglycans and proteases. Basement membranes may influence paracrine
      signalling through the binding of signalling molecules to heparan sulphate
      proteoglycans. Paracrine/autocrine actions are highly context-dependent. They are
      turned on/off when hormonal outputs need to be adapted to changing demands of the
      organism, such as during reproduction, stress, inflammation, starvation and
      circadian rhythms. Specificity and selectivity in autocrine/paracrine
      interactions may rely on microanatomical specialisations, functional
      compartmentalisation in receptor-ligand distribution and the non-equilibrium
      dynamics of the receptor-ligand interactions in the loops.

PMID- 18081576
TI  - A survey of suppression of public health information by Australian governments.
AB  - BACKGROUND: It is cause for concern when a democratically elected government
      suppresses embarrassing information by hindering public health research or the
      publication of research findings. We conducted a survey of Australian public
      health academics to estimate the level of acts of suppression of research by
      Australian governments, to characterise these events, and to gather views on what
      interventions might be effective in curbing them. METHODS: A total of 302
      academics in 17 institutions completed a postal questionnaire in August 2006 (46%
      of 652 invited). The instrument sought details of suppression events they had
      witnessed since 2001. RESULTS: There were 142 suppression events, including 85
      personally experienced by 21.2% (n=64) of respondents. The rates were higher in
      2005/06 than in earlier years. No State or Territory was immune from suppression.
      Although governments most commonly hindered research by sanitising, delaying or
      prohibiting publications (66% of events), no part of the research process was
      unaffected. Researchers commonly believed their work was targeted because it drew
      attention to failings in health services (48%), the health status of a vulnerable
      group (26%), or pointed to a harm in the environment (11%). The government agency
      seeking to suppress the health information mostly succeeded (87%) and,
      consequently, the public was left uninformed or given a false impression.
      Respondents identified a full range of participative, cognitive, structural and
      legislative control strategies. CONCLUSION: The suppression of public health
      information is widely practised by Australian governments. IMPLICATIONS: Systemic
      interventions are necessary to preserve the integrity of public health research
      conducted with government involvement.

PMID- 18081577
TI  - Barriers and facilitators to influenza vaccination among high-risk groups aged
      less than 65 years - views from general practitioners and practice nurses.
AB  - OBJECTIVES: To explore the views of general practitioners and practice nurses
      about barriers to influenza vaccination among under 65 high-risk patients and
      strategies to overcome those barriers. METHODS: Focus group discussions with
      general practitioners and practice nurses. RESULTS: Barriers identified included:
      lack of awareness among patients about influenza vaccination; GP workload; poor
      GP motivation; lack of practice nurses; lack of patient recall systems; cost of
      vaccine; and lack of media campaign. Strategies proposed included: public
      education campaigns; free supply of vaccine; dissemination of evidence to
      motivate GPs; incentives to establish recall systems; and greater involvement of
      practice nurses in the process. CONCLUSION: Influenza vaccination has not been
      well accepted by people aged less than 65 years. Implementation of proposed
      strategies has the potential to improve the vaccination coverage. IMPLICATIONS:
      An improvement in influenza vaccination coverage among people less than 65 years
      who are in high-risk groups has the potential to reduce hospitalisation and
      health care costs.

PMID- 18081578
TI  - Severe mental illness is a new risk marker for blood-borne viruses and sexually
      transmitted infections.
AB  - OBJECTIVE: To determine whether severe mental illness (SMI) constitutes a risk
      for the acquisition of sexually transmissible infections (STIs) and blood-borne
      viruses (BBVs), including human immunodeficiency virus (HIV), both locally and
      globally. METHOD: Database searches revealed 51 eligible studies for the review.
      Studies with samples of patients with SMI were analysed and compared with
      population data. RESULTS: Most studies were conducted in the United States and
      the majority examined levels of risk behaviours. The review revealed that many
      countries, including Australia, had not had any prevalence studies for STIs or
      any BBVs among patients with SMI. STIs, HIV and other BBVs, as well as risk
      behaviours, were more prevalent in patients with SMI, compared with population
      rates. Overall, a weighted mean of 4% of patients with SMI had HIV infection and
      10-20% had hepatitis C virus (HCV). CONCLUSIONS: Severe mental illness appears to
      be a risk marker for the presence of STIs, HIV and other BBVs. HIV and HCV
      prevalences were elevated for those with risk behaviour histories, but rates also
      seem elevated for patients with SMI lacking such histories when compared with the
      general population. IMPLICATIONS: Programs are needed, particularly in the United
      States, for screening all patients with SMI for STIs and BBVs to kerb this
      epidemic. Such strategies could also be applicable in Australia, but there is
      less conclusive evidence.

PMID- 18081579
TI  - Use of 'dual protection' and other combinations of contraceptive methods in
      Australia.
AB  - OBJECTIVE: To examine the demographic profiles of contraceptive users in
      Australia, paying particular attention to the use of condoms with other methods.
      METHOD: Data from a specific section on contraceptive use in the 2005 Wave 5 of
      the nationwide, longitudinal Household Income and Labour Dynamics in Australia
      (HILDA) were analysed. The section was restricted to 2,221 women aged 18-44;
      women were excluded if they were pregnant or subfecund, or if they or their
      partner had been sterilised. RESULTS: Two-thirds of respondents were using
      contraception, including more than 15% who indicated use of more than one method.
      The contraceptive pill (39%) was the most widely used method, followed by the
      condom (28%). Women using sex-related methods were more likely to be using more
      than one method. More than one-quarter of pill users (28%) were using condoms as
      well. The combination of pill and condom was significantly associated with age,
      being a student, and country of birth. Less than 3% of women reported using
      rhythm methods and of these two-thirds were using another method. CONCLUSIONS:
      Dual protection provided by the combination of the condom with the pill or other
      methods has become an important factor in the prevention of sexually transmitted
      infections and unwanted pregnancies, but continuing education on dual protection
      and better access to treatment is still necessary for both men and women,
      particularly among at-risk groups.

PMID- 18081580
TI  - Estimates for cervical abnormalities in Vanuatu.
AB  - OBJECTIVE: To use the Pap smear to establish a recent prevalence of cervical
      abnormalities within a select population in Vanuatu, a developing country.
      METHODS: Cervical smears (n=907) were collected from Ni-Vanuatu women from both
      urban and rural islands within Vanuatu between August 2001 and September 2005.
      RESULTS: The prevalence of low-grade epithelial abnormalities for the total
      population was 2.9% and the prevalence of the high-grade epithelial
      abnormalities/cancer was 2.0%. There was a significant difference (p<0.05) in
      prevalence of high-grade epithelial abnormalities/cancer between the urban and
      rural populations sampled, with a higher prevalence in the urban population.
      CONCLUSIONS: The prevalence of pre-cancer and cancer in Vanuatu is high compared
      with Victorian (Australian) statistics yet comparable with other developing
      countries with no cervical screening programs available. IMPLICATIONS: This study
      will hopefully assist in future planning of women's health programs and relevant
      preventive strategies to combat cervical cancer in Vanuatu.

PMID- 18081581
TI  - Contact tracing in a regional sexual health clinic: audit outcomes and
      implications for sexually transmissible infection control.
AB  - OBJECTIVE: To evaluate contact tracing outcomes in a regional sexual health
      clinic (SHC) and to investigate contact tracing outcome measures. METHOD: A
      retrospective audit of contact tracing activities for all 126 cases of Chlamydia
      trachomatis, 19 cases of Neisseria gonorrhoeae and two cases of early syphilis
      diagnosed during 2004 was conducted at a regional SHC in Queensland, Australia.
      RESULTS: Patient referral was used for almost all contact tracing. The ratio of
      index cases to contacts reported by the index case as known to be treated and
      seen at the clinic was 1:0.71 and 1:0.26 respectively. Ratios of index cases to
      contacts for chlamydial infection and gonorrhoea were similar. Records identified
      that past partners were treated less often than current regular partners and were
      rarely seen at the clinic. The ratio of total index cases to total clients seen
      as contacts, including contacts of index cases diagnosed elsewhere, was 1:0.52.
      IMPLICATIONS: Improving information and resources for index cases should be a
      priority of any contact tracing program, with a focus on strategies to increase
      contact tracing of past partners. A method of evaluating contact tracing
      processes can include summary outcome data such as the ratio of total index cases
      to total clients seen as contacts and the proportion of contacts testing
      positive. Such measures may be useful in evaluating new contact tracing
      strategies and may also be applicable for the development of a national standard
      for contact tracing.

PMID- 18081582
TI  - Journal impact factors: what do they mean for public health?

PMID- 18081583
TI  - Insufficient rural doctors: Maslow's theory and the need for social
      accountability.

PMID- 18081584
TI  - Response to Swinburn et al. on obesity program evaluation.

PMID- 18081588
TI  - Cyanobacterial composition of microbial mats from an Australian thermal spring: a
      polyphasic evaluation.
AB  - Cyanobacterial composition of microbial mats from an alkaline thermal spring
      issuing at 43-71 degrees C from tropical north-eastern Australia are described
      using a polyphasic approach. Eight genera and 10 species from three
      cyanobacterial orders were identified based on morphological characters. These
      represented taxa previously known as thermophilic from other continents.
      Ultrastructural analysis of the tower mats revealed two filamentous morphotypes
      contributed the majority of the biomass. Both types had ultrastructural
      characteristics of the family Pseudanabaenaceae. DNA extracts were made from
      sections of the tentaculiform towers and the microbial community analysed by 16S
      cyanobacteria-specific PCR and denaturing-gradient gel electrophoresis. Five
      significant bands were identified and sequenced. Two bands clustered closely with
      Oscillatoria amphigranulata isolated from New Zealand hot springs; one unique
      phylotype had only moderate similarity to a range of Leptolyngbya species; and
      one phylotype was closely related to a number of Geitlerinema species. Generally
      the approaches yielded complementary information, however the results suggest
      that species designation based on morphological and ultrastructural criteria
      alone often fails to recognize their true phylogenetic position. Conversely some
      molecular techniques may fail to detect rare taxa suggesting that the widest
      possible suite of techniques be applied when conducting analyses of
      cyanobacterial diversity of natural populations. This is the first polyphasic
      evaluation of thermophilic cyanobacterial communities from the Australian
      continent.

PMID- 18081589
TI  - Light enhanced amino acid uptake by dominant bacterioplankton groups in surface
      waters of the Atlantic Ocean.
AB  - (35)S-Methionine and (3)H-leucine bioassay tracer experiments were conducted on
      two meridional transatlantic cruises to assess whether dominant planktonic
      microorganisms use visible sunlight to enhance uptake of these organic molecules
      at ambient concentrations. The two numerically dominant groups of oceanic
      bacterioplankton were Prochlorococcus cyanobacteria and bacteria with low nucleic
      acid (LNA) content, comprising 60% SAR11-related cells. The results of flow
      cytometric sorting of labelled bacterioplankton cells showed that when incubated
      in the light, Prochlorococcus and LNA bacteria increased their uptake of amino
      acids on average by 50% and 23%, respectively, compared with those incubated in
      the dark. Amino acid uptake of Synechococcus cyanobacteria was also enhanced by
      visible light, but bacteria with high nucleic acid content showed no light
      stimulation. Additionally, differential uptake of the two amino acids by the
      Prochlorococcus and LNA cells was observed. The populations of these two types of
      cells on average completely accounted for the determined 22% light enhancement of
      amino acid uptake by the total bacterioplankton community, suggesting a plausible
      way of harnessing light energy for selectively transporting scarce nutrients that
      could explain the numerical dominance of these groups in situ.

PMID- 18081590
TI  - Candidatus 'Brocadia fulgida': an autofluorescent anaerobic ammonium oxidizing
      bacterium.
AB  - Anaerobic ammonium oxidizing (anammox) bacteria are detected in many natural
      ecosystems and wastewater treatment plants worldwide. This study describes the
      enrichment of anammox bacteria in the presence of acetate. The results obtained
      extend the concept that the anammox bacteria can be enriched to high densities in
      the presence of substrates for heterotrophic growth. Batch experiments showed
      that among the tested biomass, the biomass from the Candidatus 'Brocadia fulgida'
      enrichment culture oxidizes acetate at the highest rate. Continuous cultivation
      experiments showed that in the presence of acetate, ammonium, nitrite and
      nitrate, Candidatus 'Brocadia fulgida' out-competed other anammox bacteria. The
      results indicated that Candidatus 'Brocadia fulgida' did not incorporate acetate
      directly into their biomass. Candidatus 'Brocadia fulgida' exhibited the common
      characteristics of anammox bacteria: the presence of an anammoxosome and
      ladderane lipids and the production of hydrazine in the presence of
      hydroxylamine. Interestingly, the biofilm aggregates of this species showed
      strong autofluorescence. It is the only known anammox species exhibiting this
      feature. The autofluorescent extracellular polymeric substance had two excitation
      (352 and 442 nm) and two emission (464 and 521 nm) maxima.

PMID- 18081591
TI  - A strain of Lactobacillus plantarum affects segmented filamentous bacteria in the
      intestine of immunosuppressed mice.
AB  - Segmented filamentous bacteria (SFB) are present in the gastrointestinal tract of
      mice from weaning until the maturation of the immune system. Probiotic bacteria
      also have an effect on host immunity. To study the relationships established
      between these bacteria, samples from a mouse model fed with Lactobacillus
      plantarum under different immunological conditions were analysed. SFB populations
      were measured by a newly designed group-specific quantitative PCR assay. The
      results confirmed the presence of the probiotic in the intestine and an expansion
      of SFB in the ileum of immunocompromised mice, which was abolished upon
      administration of L. plantarum, an effect not described to date.

PMID- 18081592
TI  - Endophytic colonization of Vitis vinifera L. by Burkholderia phytofirmans strain
      PsJN: from the rhizosphere to inflorescence tissues.
AB  - The colonization pattern of Vitis vinifera L. by Burkholderia phytofirmans strain
      PsJN was determined using grapevine fruiting cuttings with emphasis on putative
      inflorescence colonization under nonsterile conditions. Two-week-old rooted
      plants harbouring flower bud initials, grown in nonsterile soil, were inoculated
      with PsJN:gfp2x. Plant colonization was subsequently monitored at various times
      after inoculation with plate counts and epifluorescence and/or confocal
      microscopy. Strain PsJN was chronologically detected on the root surfaces, in the
      endorhiza, inside grape inflorescence stalks, not inside preflower buds and
      flowers but rather as an endophyte inside young berries. Data demonstrated low
      endophytic populations of strain PsJN in inflorescence organs, i.e. grape stalks
      and immature berries with inconsistency among plants for bacterial colonization
      of inflorescences. Nevertheless, endophytic colonization of inflorescences by
      strain PsJN was substantial for some plants. Microscopic analysis revealed PsJN
      as a thriving endophyte in inflorescence organs after the colonization process.
      Strain PsJN was visualized colonizing the root surface, entering the endorhiza
      and spreading to grape inflorescence stalks, pedicels and then to immature
      berries through xylem vessels. In parallel to these observations, a natural
      microbial communities was also detected on and inside plants, demonstrating the
      colonization of grapevine by strain PsJN in the presence of other microorganisms.

PMID- 18081593
TI  - Enrichment of anaerobic benzene-degrading microorganisms by in situ microcosms.
AB  - Microcosms filled with different solids (sand, lava, Amberlite XAD-7) were
      exposed for 67 days in the sulfidic part of a groundwater monitoring well
      downstream of the source zone of a benzene-contaminated aquifer and subsequently
      incubated in the laboratory. Benzene was repeatedly degraded in several
      microcosms accompanied by production of sulfide, leading to stable benzene
      degrading enrichment cultures. In control microcosms without filling material,
      benzene was initially degraded, but the benzene-degrading capacity could not be
      sustained. The results indicate that long-term physiologically active benzene
      degrading microorganisms were attached to surfaces of the solids. The
      biodiversity and attachment behavior of microorganisms in the in situ microcosms
      was assessed by confocal laser scanning microscopy and single-strand conformation
      polymorphism (SSCP) analysis, followed by sequencing of dominant SSCP bands. The
      microbial community was composed of several different Bacteria, representing
      members of Clostridia, Bacteroidales, all subgroups of the Proteobacteria,
      Verrucomicrobia, Nitrospira, Chloroflexi and Chlorobi. Only a few archaeal
      sequences could be retrieved from the communities. The majority of phylotypes
      were affiliated to bacterial groups with a possible functional relationship to
      the bacterial sulfur cycle, thus indicating that the microbial community in the
      investigated aquifer zone depends mainly on inorganic sulfur compounds as
      electron donors or acceptors, a finding that corresponds to the geochemical data.

PMID- 18081596
TI  - Polycystic ovary syndrome: a transgenerational evolutionary adaptation.
AB  - Polycystic ovary syndrome has a common association with anovulatory infertility,
      while the physical symptoms are often associated with the increased androgens
      that are part of the endocrine profile. There is a well-recognised association
      with lipid and glucose metabolism anomalies and, when undergoing ovulation
      induction, ovarian hyperstimulation syndrome. This common condition is familial,
      but a contributory gene has yet to be found. The question of why a gene that
      predisposes to anovulation, diabetes and heart disease might have perpetuated so
      frequently is addressed. Three hypotheses for evolutionary advantage are
      discussed. The food deprivation hypothesis considers the role of the observed
      increase in ovulation when women with the condition lose weight in relation to
      seasonality. The refeeding hypothesis considers the androgenic and slightly
      enhanced anabolic metabolism in relation to periods of privation and the
      advantage of preferential early ovulation when refeeding after a period of
      privation. The transgenerational privation hypothesis considers the effect of
      persistent, severe, yet subfatal privation on individuals both in utero and
      throughout life. While an androgenic, anabolic state would improve efficiency in
      the use of food for protein synthesis and fat storage, benefiting the fetus both
      in relation to its in utero development and neonatal survival, survival and
      reproductive capacity as an adult benefits by a genotype expressing itself in
      women of successive generations.

PMID- 18081597
TI  - Developmental mismatch: consequences for later cardiorespiratory health.
AB  - Clinical and epidemiological studies have established that people who were small
      at birth and had poor infant growth have an increased risk of adult
      cardiovascular and respiratory disease, particularly if their restricted early
      growth is followed by accelerated childhood weight gain. This relationship
      extends across the normal range of infant size in a graded manner. The 'mismatch
      hypothesis' proposes that ill health in later life originates through
      developmental plastic responses made by the fetus and infant; these responses
      increase the risk of adult disease if the environment in childhood and adult life
      differs from that predicted during early development.

PMID- 18081598
TI  - Hormone replacement therapy use and variations in the risk of breast cancer.
AB  - OBJECTIVE: To determine the effect of different types and formulations of hormone
      replacement therapy (HRT) on the risk of breast cancer in postmenopausal women.
      DESIGN: Population-based case-control study. SETTING: UK, 1988-2004.
      PARTICIPANTS: Women 50-75 years between 1998 and 2004. MAIN OUTCOME MEASURES:
      Breast cancer incidence to estimate the rate ratio (RR) associated with use of
      various HRTs over a 30-year period. RESULTS: We identified 6347 incident cases of
      breast cancer that were matched with 31,516 controls. Cases were on average 61
      years at diagnosis and 22% had undergone a hysterectomy. The rate of breast
      cancer was increased with the use of opposed estrogens in oral form (adjusted RR
      1.38; 95% CI 1.27-1.49) in contrast to patch form (RR 1.08; 95% CI 0.81-1.43).
      This rate was similarly elevated with both continuous (RR 1.29; 95% CI 1.07-1.56)
      and sequential (RR 1.33; 95% CI 1.21-1.46) forms of opposed estrogen. The rate of
      breast cancer was not increased among exclusive users of unopposed estrogens (RR
      0.97; 95% CI 0.86-1.09) or of tibolone (RR 0.86; 95% CI 0.65-1.13). Users of
      tibolone who had switched from opposed estrogens, however, had an elevated rate
      (RR 1.29; 95% CI 1.09-1.52). The rate of breast cancer increased by 25% (95% CI
      20-30%) with every ten prescriptions of orally administered opposed estrogen.
      CONCLUSIONS: The risk of breast cancer varies with the formulation and
      preparation of HRT. Opposed estrogens (progesterone-estrogen) in oral form are
      associated with an increased risk of breast cancer, which increases with use.
      Transdermal opposed estrogens, unopposed estrogens and tibolone do not increase
      this risk. However, this study is an observational study that carries risks of
      various biases, and thus the findings need to be interpreted with caution.

PMID- 18081599
TI  - A prospective longitudinal population-based study of clinical miscarriage in an
      urban Swedish population.
AB  - OBJECTIVE: To describe the incidence of clinical miscarriage and to investigate
      the factors influencing the occurrence of clinical miscarriage. DESIGN:
      Prospective study with both cross-sectional and longitudinal comparisons.
      SETTING: City of Goteborg, Sweden. POPULATION: Population-based study in cohorts
      of 19-year-old women followed longitudinally. MAIN OUTCOME MEASURES: Incidence of
      miscarriage and pregnancy outcome. MATERIAL AND METHODS: A postal questionnaire
      was sent to women born in 1962 and resident in the city of Goteborg in 1981 (n =
      656) regarding pregnancy outcome, clinical miscarriage and other reproductive
      health factors. Responders in 1981 were contacted again and requested to answer a
      similar questionnaire every fifth year up to 2001. The same process was repeated
      in 1991 with women born in 1972 (n = 780) with follow up of these responders in
      1996 and 2001. A third cohort of 19-year-old women born in 1982 (n = 666) was
      interviewed in 2001. The self-reported pregnancy data were verified from hospital
      files. RESULTS: Complete data were available for 341 women born in 1962 and
      assessed up to the age of 39 years (ever pregnant, n = 320, 94%). There were in
      total 887 pregnancies (live birth, n = 590, 67%; miscarriage, n = 108, 12%; legal
      abortion, n = 173, 20% and ectopic pregnancy, n = 16, 2%). Of the 320 'ever
      pregnant' women, 80 women (25%) had experienced a miscarriage. 76.3% had
      experienced one miscarriage, 16.3% had two miscarriages and 7.4% had three or
      more miscarriages. The clinical miscarriage rates in women at different ages were
      as follows: 20-24 years 13.5%, 25-29 years 12.3%, 30-34 years 10.3% and 35-39
      years 17.5%. The corresponding miscarriage rate in the 1972 cohort followed from
      19 to 29 years of age was 11%, and in the 1982 cohort assessed at 19 years of
      age, the miscarriage rate was 9%. No risk factor for miscarriage could be
      reliably identified. CONCLUSIONS: Clinical miscarriage constituted 12% of all
      pregnancies, and one in four women who had been pregnant up to 39 years of age
      had experienced a miscarriage. Three or more miscarriages were experienced by
      7.4%. The occurrence of a miscarriage was not influenced by the order of the
      pregnancy.

PMID- 18081600
TI  - Is adiposity across life associated with subsequent hysterectomy risk? Findings
      from the 1946 British birth cohort study.
AB  - OBJECTIVE: To examine the associations between adiposity at time points from
      early life onwards and subsequent hysterectomy risk. DESIGN: Prospective birth
      cohort study. SETTING: England, Scotland and Wales. POPULATION: Women from the
      Medical Research Council National Survey of Health and Development study, with
      complete data on hysterectomy status (n= 1790). METHODS: Survival analysis
      methods were used to examine the associations between body mass index at time
      points across life and subsequent hysterectomy rates. MAIN OUTCOME MEASURE: Self
      reported hysterectomy with or without oophorectomy. RESULTS: From 20 years
      onwards, those women who were classified as underweight had lower hysterectomy
      rates, and from 36 years onwards, those women who were overweight had higher
      hysterectomy rates than those who were normal weight. Women who were obese in
      adolescence and early adulthood had lower rates of hysterectomy than those who
      were normal weight, although numbers categorised as obese at these ages were
      small. Women who were obese in later adulthood had higher subsequent rates of
      hysterectomy. Greater increases in weight between ages 36 and 53 years were
      associated with higher rates of hysterectomy in later adulthood. These results
      were not explained by parity, age at menarche or socio-economic position.
      CONCLUSIONS: These results suggest that variation in hysterectomy rates may be
      partially explained by variation in adiposity, and so with the recent changes in
      levels of overweight and obesity in populations, there may be increasing demand
      for gynaecological treatments in the future.

PMID- 18081601
TI  - A 2-year follow-up study of anxiety and depression in women referred for
      colposcopy after an abnormal cervical smear.
AB  - OBJECTIVES: The aim of this study was to determine if there were any long-lasting
      elevated anxiety levels in women attending colposcopy after an abnormal cervical
      smear. DESIGN: Prospective study. SETTING: Department of Obstetrics and
      Gynaecology, Malmo University Hospital, Sweden. POPULATION: One hundred
      consecutive women were invited to participate when referred for colposcopy.
      METHODS: Women in the study group completed the State-Trait Anxiety Inventory,
      the Montgomery-Asberg Depression Rating Scale-self-rate (MADRS-S) and had a
      psychosocial interview prior to colposcopy at their two follow-up visits. MAIN
      OUTCOME MEASURES: State anxiety levels and depression scores at first visit, 6
      months and 2 years. RESULTS: At follow up, levels of state anxiety and the
      depression scores of the women studied had decreased and were comparable to those
      of Swedish normative data. Two variables from the MADRS-S, 'ability to focus on
      different activities' and 'emotional involvement with others and in activities'
      were the most prominent for women with moderate to severe depression. At the 2
      year visit, 30% of the women still had a fear of cancer. CONCLUSIONS: Referral
      for colposcopy after an abnormal cervical smear does not seem to result in long
      lasting anxiety and depression. However, a subgroup of women, with the initially
      highest depression scores, still had at 2-year state anxiety levels and
      depression scores significantly higher than normal. Almost one-third of the women
      still had a fear of cancer in spite of lower 2-year state anxiety levels.

PMID- 18081602
TI  - Randomised trial of laparoscopic Burch colposuspension versus tension-free
      vaginal tape: long-term follow up.
AB  - OBJECTIVE: To compare the long-term efficacy of laparoscopic Burch
      colposuspension with tension-free vaginal tape (TVT) for the treatment of
      urodynamic stress urinary incontinence (SUI). DESIGN: Long-term follow up from a
      prospective randomised trial. SETTING: Academic tertiary referral centre. SAMPLE:
      Seventy-two women with urodynamic SUI from two institutions. METHODS: Subjects
      were randomised to either laparoscopic Burch or TVT from August 1999 to August
      2002. Follow-up evaluations occurred 6 months, 1 year, 2 years, and 4-8 years
      after surgery. MAIN OUTCOME MEASURES: Subjects completed the Incontinence
      Severity Index, Urogenital Distress Inventory 6 (UDI-6), Incontinence Impact
      Questionnaire (IIQ-7), and Patient Global Impression of Improvement (PGI-I)
      scales. RESULTS: Median follow-up duration was 65 months (range 12-88 months)
      with 92% completing at least one follow-up visit. Seventy-four percent of
      subjects had long-term (4-8 years) follow up. Fifty-eight percent of subjects
      receiving laparoscopic Burch compared with 48% of TVT subjects reported any
      urinary incontinence 4-8 years after surgery (Relative Risk (RR):1.19; 95% CI:
      0.71-2.0) with no significant difference between groups. Bothersome SUI symptoms
      were seen in 11 and 8%, respectively, 4-8 years after surgery (P = 0.26). There
      was significant improvement in the postoperative UDI-6 and IIQ-7 scores in both
      groups at 1-2 years that were maintained throughout follow up with no significant
      differences between the groups. CONCLUSIONS: TVT has similar long-term efficacy
      to laparoscopic Burch for the treatment of SUI. A substantial proportion of
      subjects have some degree of urinary incontinence 4-8 years after surgery;
      however, the majority of incontinence is not bothersome.

PMID- 18081603
TI  - Diabetes mellitus following gestational diabetes: role of subsequent pregnancy.
AB  - OBJECTIVE: This study was designed to determine the rate of diabetes up to 13
      years after pregnancies complicated by gestational diabetes and to identify risk
      factors for developing diabetes. The role of a subsequent pregnancy, with and
      without gestational diabetes, was also examined. DESIGN: This was a retrospective
      cohort study of women with gestational diabetes. POPULATION AND SETTING: Women
      who had gestational diabetes in their first pregnancy between 1989 and 2002 were
      identified through a population-based perinatal database in Nova Scotia, Canada.
      METHODS: Subsequent diagnoses of diabetes, up to 13 years after the first
      pregnancy, were obtained from physician billing and hospital discharge databases.
      Cox proportional hazards regression models were used to estimate adjusted
      relative risks (RR) and 95% confidence intervals. MAIN OUTCOME MEASURES:
      Diagnosis of diabetes after pregnancy. RESULTS: Of the 1401 nulliparous women
      with gestational diabetes, 251 women (17.9%) developed diabetes in the follow-up
      period. The cumulative incidence at 1, 5, and 10 years was 5.9, 14.8, and 22.2%,
      respectively. Factors significantly associated with an increased risk of
      developing diabetes mellitus included a pre-pregnancy weight of > or = 86 kg (RR
      = 1.8, 95% CI 1.2-2.9), insulin therapy during the index pregnancy (RR = 4.1, 95%
      CI 2.1-7.9), neonatal hypoglycaemia (RR = 2.6, 95% CI 1.6-4.2), and a subsequent
      pregnancy with gestational diabetes (RR = 2.3, 95% CI 1.6-3.4). CONCLUSION:
      Indicators of the severity of gestational diabetes, defined by insulin use,
      neonatal hypoglycaemia, and recurrent gestational diabetes in a subsequent
      pregnancy, are important in predicting a subsequent diagnosis of diabetes. Our
      findings do not support the theory that subsequent pregnancy, per se, increases
      the risk of developing diabetes.

PMID- 18081604
TI  - The carotid bodies influence growth responses to moderate maternal undernutrition
      in late-gestation fetal sheep.
AB  - OBJECTIVE: To determine the role of carotid sinus innervation on differential
      fetal organ growth during maternal nutrient restriction in late pregnancy.
      DESIGN: Randomised controlled study. SETTING: University research facility.
      SAMPLE: Thirty-nine Merino ewes. METHODS: At 113 days gestational age (dGA),
      fetuses were bilaterally carotid sinus denervated or sham denervated. From 118
      dGA, the surgery groups were subdivided into two dietary groups, and their ewes
      were fed 100% of nutrient requirements or 50% until tissue collection at 140 dGA.
      This provided four groups (sham/control diet, sham/restricted diet,
      denervated/control diet and denervated/restricted diet). MAIN OUTCOME MEASURES:
      Fetal organ weights and hormone levels and maternal weight change during the
      dietary restriction. RESULTS: Adrenal glands were larger in sham/restricted diet
      fetuses than in sham/control diet or denervated/restricted diet fetuses (P <
      0.05). Fetal adrenal weight and brain-to-liver weight ratio were positively
      related to maternal weight change during the nutritional challenge in sham
      fetuses only (P < 0.05). Fetal liver weight was negatively related to maternal
      weight change during nutritional challenge in sham fetuses only (P < 0.05).
      CONCLUSIONS: We have shown a reduction in liver growth but sparing of adrenal
      growth in response to moderate maternal undernutrition, which is dependent on
      intact carotid body innervation. This suggests a new role for the carotid bodies
      in the control of differential organ growth during such undernutrition.

PMID- 18081607
TI  - What's in a name? Proposed name changes of the US National Institute on Drug
      Abuse and the US National Institute on Alcohol Abuse and Alcoholism.

PMID- 18081605
TI  - Obstetric outcomes subsequent to intrauterine death in the first pregnancy.
AB  - OBJECTIVE: To compare obstetric outcomes in the pregnancy subsequent to
      intrauterine death with that following live birth in first pregnancy. DESIGN:
      Retrospective cohort study. SETTING: Grampian region of Scotland, UK. POPULATION:
      All women who had their first and second deliveries in Grampian between 1976 and
      2006. METHODS: All women delivering for the first time between 1976 and 2002 had
      follow up until 2006 to study their next pregnancy. Those women who had an
      intrauterine death in their first pregnancy formed the exposed cohort, while
      those who had a live birth formed the unexposed cohort. MAIN OUTCOME MEASURES:
      Maternal and neonatal outcomes in the second pregnancy, including pre-eclampsia,
      placental abruption, induction of labour, instrumental delivery, caesarean
      delivery, malpresentation, prematurity, low birthweight and stillbirth. RESULTS:
      The exposed cohort (n = 364) was at increased risk of pre-eclampsia (OR 3.1, 95%
      CI 1.7-5.7); placental abruption (OR 9.4, 95% CI 4.5-19.7); induction of labour
      (OR 3.2, 95% CI 2.4-4.2); instrumental delivery (OR 2.0, 95% CI 1.4-3.0);
      elective (OR 3.1, 95% CI 2-4.8) and emergency caesarean deliveries (OR 2.1, 95%
      CI 1.5-3.0); and prematurity (OR 2.8, 95% CI 1.9-4.2), low birthweight (OR 2.8,
      95% CI 1.7-4.5) and malpresentation (OR 2.8, 95% CI 2.0-3.9) of the infant as
      compared with the unexposed cohort (n = 33,715). The adjusted odds ratio for
      stillbirth was 1.2 and 95% CI 0.4-3.4. CONCLUSION: While the majority of women
      with a previous stillbirth have a live birth in the subsequent pregnancy, they
      are a high-risk group with an increased incidence of adverse maternal and
      neonatal outcomes.

PMID- 18081609
TI  - Closing remarks: addiction societies as valuable assets.

PMID- 18081606
TI  - Impact of the use of antenatal corticosteroids on mortality, cerebral lesions and
      5-year neurodevelopmental outcomes of very preterm infants: the EPIPAGE cohort
      study.
AB  - OBJECTIVE: To assess the impact of antenatal corticosteroids (ACS) on neonatal
      mortality, cerebral lesions and 5-year neurodevelopmental outcome of infants born
      at 24-27 and 28-32 weeks of gestational age (GA). DESIGN: Observational
      population-based study including all births at GAs between 22 and 32 weeks in
      1997 in nine regions of France. Survivors were assessed at the age of 5 years.
      SAMPLE AND METHODS: The population enrolled in the follow up comprised 2323
      infants; there were 23 deaths before age 5 years and outcome at 5 years was
      available for up to 1781 subjects. Two GA subgroups (24-27 and 28-32 weeks of GA)
      were analysed separately. Propensity scores were used to reduce bias in the
      estimation of the association between ACS treatment and outcomes. MAIN OUTCOME
      MEASURES: Neonatal death, neonatal white matter injury, cerebral palsy, mental
      processing composite (MPC) of the Kaufman Assessment Battery for Children test
      and behavioural difficulties at 5 years. RESULTS: In the 28- to 32-week GA
      subgroup, there was a significant association between ACS and a decreased risk of
      both neonatal death (OR = 0.61 [0.41-0.91]) and white matter injury (OR = 0.60
      [0.46-0.79]) but only a nonsignificant trend for improved 5-year outcome
      (cerebral palsy, MPC < 70). In the 24- to 27-week GA subgroup, ACS was associated
      with a significant decrease risk of neonatal death (OR = 0.43 [0.27-0.68]) but
      there was only a trend for a lower risk of white matter injury and no beneficial
      impact on outcome at 5 years. Limiting the analysis to only those who received
      complete courses of ACS did not modify the results. CONCLUSION: The study shows
      that ACS therapy greatly increases the survival of very preterm infants,
      including the most immature, but there is little evidence that ACS affects long
      term neurodevelopmental and behavioural outcome in 28- to 32-week survivors, and
      none in <28-week survivors.

PMID- 18081610
TI  - Conversation with Rudolf Moos.

PMID- 18081611
TI  - Regression to the mean in addiction research.

PMID- 18081612
TI  - Alcohol and violence: a complex nexus of drinking environment and drinking
      pattern.

PMID- 18081613
TI  - The clinical fallacy and treatment outcomes.

PMID- 18081614
TI  - Rural-urban migration, illicit drug use and hazardous/harmful drinking in the
      young Thai population.
AB  - AIMS: Limited data are available about whether rural-urban migration, often
      characterized by exposure to urban life stress and a reduction in social network
      and support, can affect the prevalence of illicit drug use and hazardous/harmful
      drinking. The purpose of our study was to examine the prevalence of these risky
      behaviours among Thai young adults and to describe their association between
      their migration status and these outcomes. DESIGN: A population-based cross
      sectional survey. SETTING: A representative sample of 1052 residents, aged 16-25
      years (467 males and 585 females) in a suburban community of Bangkok in 2003 and
      2004. MEASUREMENTS: (i) Exposures-migration (defined as the occasion when a young
      person born in a more rural area moves for the first time into Greater Bangkok);
      and (ii) outcomes-illicit drug use was assessed with an anonymous self-report
      adapted from the Diagnostic Interview Schedule (DIS) and hazardous/harmful
      drinking with Alcohol Use Disorder Identification Test (AUDIT). FINDINGS: The
      results showed that 10.9% (82 males and 17 females) had illicit drug use and
      24.3% (179 males and 62 females) hazardous and harmful drinking. In multivariate
      analysis, rural-urban migration was not associated with illicit drug use, whereas
      hazardous/harmful drinking was associated independently with being late migrants,
      who moved at the age of 15 or older. CONCLUSIONS: Illicit drug use and
      hazardous/harmful drinking were common among young Thais. The potential effect of
      migration on hazardous and harmful drinking identified in this study may be
      helpful for the design and implementation of preventive measures.

PMID- 18081615
TI  - Value-added education and smoking uptake in schools: a cohort study.
AB  - AIM: To show that schools achieving higher examination pass and lower truancy
      rates than expected, given that their pupil populations (high value-added
      schools) are associated with a lower incidence of smoking among pupils (13-14
      years). DESIGN: Value-added scores for schools were derived from standardized
      residuals of two regression equations predicting separately the proportion of
      pupils passing high school diplomas and the half-days lost to truancy from the
      socio-economic and ethnic profiles of pupils. The risk of regular smoking at 1-
      and 2-year follow-up was examined in relation to the value-added score in a
      cohort of 8352 UK pupils. Random-effects logistic regression was used to adjust
      for baseline smoking status and other adolescent smoking risk factors. SETTING: A
      total of 52 schools, West Midlands, UK. PARTICIPANTS: Year 9 pupils aged 13-14
      years (n = 8352) were followed-up after 1 year (n = 7444; 89.1% of original
      cohort) and 2 years (n = 6819; 84.6% of original cohort excluding pupils from two
      schools that dropped out). MEASUREMENTS: Regular smoking (at least one cigarette
      per week). FINDINGS: Schools with high value-added scores occurred throughout the
      socio-demographic spectrum. The odds ratio (95% confidence interval) for regular
      smoking for a 1 standard deviation increase in the value-added measure was 0.85
      (0.73-0.99) at 1-year and 0.80 (0.71-0.91) at 2-year follow-ups. Baseline smoking
      status did not moderate this. CONCLUSIONS: Schools with high value-added scores
      are associated with lower incidence of smoking. Some schools appear to break the
      strong link between deprivation and smoking. Understanding the mechanisms could
      be of great public health significance.

PMID- 18081616
TI  - Widespread cognitive impairment in psychogenic anterograde amnesia.
AB  - A 34-year-old man without a past history of any psychiatric or neurological
      disorder developed severe anterograde amnesia following a psychological trauma.
      Initial assessment of neuropsychological functions 3 months after the
      psychological trauma indicated severe memory deficits for acquiring new
      information in both verbal and visual modalities with widespread cognitive
      deficits in attention, executive functions, and intellectual ability.
      Importantly, working and remote memory were intact. The case illustrates that
      psychogenic anterograde amnesia might be associated with a wider range of
      cognitive deficits. Possible neurobiological explanations are discussed to
      explain large cognitive impairments associated with anterograde psychogenic
      amnesia.

PMID- 18081617
TI  - Sociodemographic and clinical factors associated with relapse in schizophrenia.
AB  - The aim of the present study was to examine sociodemographic and clinical factors
      associated with relapse in schizophrenia. The study group consisted of a
      convenience sample of 40 schizophrenia patients (20 patients each in relapse and
      remission). Relapse and remission were defined based on clinical criteria (ICD-10
      criteria, course since last episode, and duration of remission) and psychometric
      criteria (scores on Socio-Occupational Functioning Assessment Scale [SOFAS] and
      Positive and Negative Syndrome Scale for Schizophrenia [PANSS]). The index group
      was evaluated after the occurrence of current relapse but within 6 months of its
      onset. Sociodemographic, current psychopathology (PANSS) and functioning (SOFAS),
      and other (mainly retrospective) variables were assessed with a specifically
      designed clinical profile sheet, Schedule for Affective Disorders and
      Schizophrenia Lifetime version, Presumptive Stressful life Events Scale, and
      World Health Organization Life Chart Schedule for Assessment of Course and
      Outcome of Schizophrenia. Patients who had relapsed were more symptomatic and
      exhibited greater dysfunction in comparison to remitted patients. Relapse in
      schizophrenia was significantly associated with unemployment, number of psychotic
      episodes, side-effects of medication, and life events score. The present findings
      suggest that a severe illness (no. psychotic episodes, unemployment),
      psychological stress and inappropriate treatment (side-effects of medicines) may
      be causally related to relapse in schizophrenia. However, the possibility that
      these variables may be caused by relapse or may be explained by a common
      underlying variable needs to be assessed prospectively.

PMID- 18081618
TI  - Application of Empowerment Scale to patients with schizophrenia: Japanese
      experience.
AB  - Rogers et al. invented the Empowerment Scale, and conducted a factor analysis,
      which found five factors: self-esteem, power, activism, righteous anger and
      optimism. Hata et al. translated this scale into Japanese and named it
      Empowerment Scale-J. They found that the score of the righteous anger factor does
      not have a significant correlation with the overall score of the Empowerment
      Score-J. With the aim of clarifying the characteristics of the Empowerment Scale
      J, the purpose of the present study was to assess the levels of empowerment in 72
      Japanese patients with chronic schizophrenia using the scale, and examine the
      relationship between the results of the scale and the results of the following
      two batteries: Social Adjustment Scale II (SAS II), and Expanded Attributional
      Style Questionnaire (EASQ; a questionnaire to assess some aspects of attitude
      toward negative circumstances). Four results were obtained as follows. No
      significant correlation was found between the score of righteous anger factor and
      overall score. No significant correlation was found between the Empowerment Scale
      J score and the degree of social adjustment. Significant correlations were found
      between some subscales of Empowerment Scale-J and the degree of social
      adjustments: self-esteem and optimism, but inverse correlations were obtained
      between the power factor and the righteous anger factor and the degree of social
      adjustment. Results for the EASQ showed that subjects with a higher righteous
      anger score have a tendency opposite to that of subjects with higher social
      adjustment. On the basis of these results it is suggested that behavior related
      to the righteous anger among Japanese persons with schizophrenia may have some
      negative influence on their social adaptation and that in applying Empowerment
      scale-J attention should be paid to the significance of the righteous anger
      factor.

PMID- 18081619
TI  - Brief assessment of cognition in schizophrenia: validation of the Japanese
      version.
AB  - This preliminary study was performed to test the reliability and validity of the
      Brief Assessment of Cognition in Schizophrenia (BACS) as an assessment tool in a
      Japanese-language version (BACS-J). The subjects for the present study were 30
      outpatients with chronic schizophrenia. Each subject gave written informed
      consent to participate in the research. Cronbach's alpha for the BACS-J was 0.77.
      The BACS-J composite score was significantly correlated with all primary measures
      of BACS-J (verbal memory, working memory, motor speed, verbal fluency, attention,
      and executive function). All BACS-J primary measures and the composite score were
      significantly correlated between two assessments. The mean score of the Digit
      Sequencing Task and composite score on the second assessment were significantly
      larger than those on the first assessment. All BACS-J primary measures except the
      Symbol Coding Task were significantly correlated with relevant standard
      neurocognitive tests. Also, the BACS-J composite score was significantly
      correlated with all standard neurocognitive tests except the Continuous
      Performance Test. A principal components analysis with varimax rotation resulted
      in a three-factor solution (executive function and memory; motor speed and
      general cognitive functions; and working memory). This preliminary study
      indicates that the BACS-J is a reliable and practical scale to evaluate cognitive
      function.

PMID- 18081620
TI  - Factors related to quality of life in depressive outpatients in Taiwan.
AB  - Issues related to recovery of quality of life (QoL) in depressive outpatients
      have been raised. This descriptive correlation study investigated QoL in
      depressive outpatients in Taiwan. A total of 181 depressive outpatients
      participated in the study. Their QoL levels were measured using the Taiwanese
      version of the Short Form of the World Health Organization Quality of Life
      questionnaire (WHOQOL-BREF). The results indicate that multiple predicting
      factors including marriage, less severity of depression, better social support,
      and better medical professional-patient interaction are associated with better
      QoL in depressive outpatients in the physical, psychological, social
      relationship, and environmental domains. QoL and its correlation with depressive
      outpatients must be emphasized in order to develop appropriate strategies to
      improve QoL and treatment efficacy.

PMID- 18081621
TI  - Activation of the prefrontal cortex during the Trail-Making Test detected with
      multichannel near-infrared spectroscopy.
AB  - The Trail-Making Test (TMT) is a neuropsychological test for evaluating executive
      function, and the TMT Part B reflects more complex cognitive processes including
      cognitive set shifting. The prefrontal cortex (PFC) is thought to be involved in
      these cognitive processes. The purpose of the present paper was to investigate
      PFC activation during performance of the TMT Part A and Part B using multichannel
      near-infrared spectroscopy (NIRS). Subjects were 41 healthy right-handed
      volunteers. The hemodynamic changes in the PFC during the TMT were measured on a
      22-channel NIRS machine. The subjects had a greater increase of oxygenated
      hemoglobin ([oxyHb]) during the TMT Part B than during Part A in the PFC. Twenty
      seven out of the 41 subjects had a bilateral increase of [oxyHb] in the PFC
      during Part B according to laterality index. NIRS detected activation in the PFC
      during the performance of the TMT Part B and this PFC activation may reflect
      executive functions including cognitive set shifting involved in the TMT Part B.

PMID- 18081622
TI  - Risperidone, olanzapine and quetiapine in the treatment of behavioral and
      psychological symptoms in patients with Alzheimer's disease: preliminary findings
      from a naturalistic, retrospective study.
AB  - The objectives of this retrospective, naturalistic study were to provide
      preliminary data on the effects of 6 months treatment with risperidone,
      olanzapine and quetiapine on behavioral disturbances, within a sample of
      outpatients with mild to moderate Alzheimer's disease, and on predictors of
      response. Between July 2005 and December 2005, data were collected from 58
      consecutive outpatients with a DSM-IV-TR diagnosis of Alzheimer's disease with
      behavioral disturbances, who received a 6-month treatment with risperidone,
      olanzapine or quetiapine. Primary outcome measures were Neuropsychiatric
      Inventory (NPI) total score and its items forming the basic core of behavioral
      disturbances in Alzheimer's disease: delusions, hallucinations and
      agitation/aggressiveness. Secondary outcome measures were Mini-Mental State
      Examination (MMSE), Activities of Daily Living, Instrumental Activities of Daily
      Living and Clinical Insight Rating scale. Correlations between baseline MMSE
      score and improvements in behavioral disturbances were investigated. At 6 months
      mean NPI total score had fallen 43.5% in the risperidone group, 45.6% in the
      olanzapine group and 33.3% in the quetiapine group, with no significant between
      group differences. Global cognitive function showed no significant change from
      baseline to end-point. Incidence of adverse events was low. A significant
      correlation was found between MMSE score and NPI total score and NPI item
      agitation decreases. Risperidone, olanzapine and quetiapine produced significant
      improvements in behavioral disturbances and were well tolerated. No significant
      differences emerged among treatments. The preliminary results also suggest that
      baseline cognitive function might influence treatment response.

PMID- 18081623
TI  - Use of low-dose topiramate in substance use disorder and bodyweight control.
AB  - In recent years topiramate has been used for psychiatric patients, mainly for
      controlling substance use and food intake. A total of 46 patients who received
      topiramate treatment during the study period were identified from a computer
      database. Nineteen had received topiramate for at least 1 month. Twelve patients
      received topiramate for anticraving effects (alcohol, n = 9; heroin/amphetamine,
      n = 1; meperidine, n = 1; and nicotine, n = 1). On an average dosage of 112.5
      mg/day, nine of the 12 patients (excluding three alcoholic patients) achieved
      complete or partial remission from the substance use disorders. The present
      results show that six of the nine patients achieved full or partial remission
      from alcohol use disorder on a dosage of 100 mg/day. Topiramate was also used to
      control seven patients' bodyweight (mean bodyweight change, 1.53 kg). Four of
      them achieved bodyweight loss in the 1-month follow up, with an average change of
      2.65 kg. Based on the present findings topiramate <100 mg/day may be effective in
      treating patient with alcohol use disorder, and that topiramate has not shown
      remarkable benefit of bodyweight loss.

PMID- 18081624
TI  - Cognitive insight and acute psychosis in schizophrenia.
AB  - Cognitive insight is a new concept. There are very few data regarding the
      relationship between cognitive insight and positive symptoms. The goal of the
      present study was to investigate the impact of acute psychosis (delusions and
      hallucinations) on overconfidence in judgments and self-reflectiveness of
      patients with schizophrenia. The Beck Cognitive Insight Scale was used to compare
      the cognitive insight of schizophrenia patients with (n = 93) and without (n =
      45) current psychotic symptoms. Clinical symptoms and clinical insight of the
      patients were also assessed. The present findings suggest that both
      overconfidence in judgments and impaired self-reflectiveness are associated with
      acute psychosis. Only diminished self-reflectiveness seem to be improved
      following hospitalization. Although overconfidence of schizophrenia patients in
      their judgments was more severe in schizophrenia patients with psychotic
      symptoms, self-certainty of schizophrenia patients may be a relatively persistent
      characteristic that is also present after recovery of psychosis. Studies with
      larger samples involving follow up for longer periods will be valuable to
      understand the nature of the relationship between cognitive insight and clinical
      symptoms of schizophrenia.

PMID- 18081625
TI  - Auditory hallucination coping techniques and their relationship to psychotic
      symptomatology.
AB  - Use of coping techniques is of importance in the treatment for patients
      experiencing auditory hallucinations. Phenomenological features of auditory
      hallucinations and other psychotic symptoms are assumed to be factors influencing
      the coping activities. The aim of the present study was to determine psychotic
      symptoms including auditory hallucination phenomenological features that have
      effects on coping activities. The authors investigated 17 generally used coping
      techniques of 144 chronically psychotic patients who were currently experiencing
      auditory hallucination in DSM-IV schizophrenia or schizoaffective psychosis.
      Using factor analysis, scales characterizing the styles of coping application and
      efficacy were constructed. To assess the phenomenological features, the authors
      used the Matsuzawa Assessment Schedule for Auditory Hallucination (MASAH), which
      had been devised to assess four basic phenomenological features: intractability,
      delusion, influence, and externality. The Positive and Negative Syndrome Scale
      (PANSS) was also applied for the assessment of psychotic symptoms. Regression
      analyses were conducted to determine the features and symptoms that could have
      effects on coping activities. Constructed scales were those of distraction and
      counteraction styles for each of coping application and efficacy. It was found
      that MASAH influence and externality features had an activating effect on both
      distraction and counteraction coping application, and counteraction coping
      application, respectively, and that PANSS negative symptom clusters and MASAH
      delusion feature had an inhibiting effect on distraction and counteraction coping
      application, respectively. No salient factor for coping efficacy was recognized.
      The current study presents information on the relationship between coping
      activities and the psychotic experience features and symptoms, which can be of
      help for planning coping training programs.

PMID- 18081626
TI  - Age of onset has limited association with body mass index at time of presentation
      for anorexia nervosa: comparison of peak-onset and late-onset anorexia nervosa
      groups.
AB  - The clinical characteristics differentiating late-onset anorexia nervosa (AN)
      from typical pubertal onset AN remain unclear. The purpose of the present study
      was to examine these differences in a retrospective analysis. A total of 149
      female AN patients was divided into two groups: a peak-onset AN group (n = 125)
      in which onset occurred between the ages of 15 and 24 years, and a late-onset AN
      group (n = 24) in which onset occurred at the age of > or =25 years. A logistic
      regression analysis was conducted with this classification as the target variable
      and five clinical factors as explanatory variables for the clinical
      characteristics at the time of initial examination. Body mass index (BMI) at the
      time of presentation was identified as a possible factor affecting classification
      as peak-onset or late-onset AN. In addition, a negative linear correlation was
      detected between age of onset and BMI at the time of initial examination. The
      results suggest that BMI at the time of the initial examination is an important
      clinical characteristic to differentiate peak-onset AN and late-onset AN.

PMID- 18081627
TI  - Emotional distress and its correlates among parents of children with pervasive
      developmental disorders.
AB  - A number of studies have reported that parents of autistic children face higher
      levels of stress, but few studies examined the stress associated with the home
      care of children with pervasive developmental disorders (PDD) other than autistic
      disorder. The aims of the present study were therefore to (i) evaluate the
      emotional stress level of parents caring for their children with PDD; and (ii)
      explore the correlates of their emotional stress. Participants were 147 families
      (147 mothers and 122 fathers) of 158 children with PDD (42 with autistic
      disorder, 35 with Asperger's disorder and 81 with PDD not otherwise specified).
      K6 was used to measure the stress level of the parents. Marital relationships and
      personality were assessed with the Intimate Bond Measure and the NEO Five-Factor
      Inventory, respectively. The parents also rated the characteristics of their
      children with PDD through the Pervasive Developmental Disorder-Autism Society
      Japan Rating Scale (PARS). The mean K6 score of the mothers was significantly
      higher than that of the women in the general population in Japan. Stepwise
      multiple regression indicated that the emotional stress of the mothers was
      correlated with the personality traits of Neuroticism and Agreeableness,
      perceived Control by the husband, and the children's PARS score. Clinicians can
      deliver better service by paying appropriate attention to the emotional distress
      of mothers of children with not only autistic disorder but also other PDD.

PMID- 18081628
TI  - Reliability and validity of questionnaire for neurobehavioral disability
      following traumatic brain injury.
AB  - The neurobehavioral disability recognized in traumatic brain injury (TBI) is a
      severe sequela, but there is no appropriate classification due to its various
      manifestations. In the present study a questionnaire for a simple investigation
      of this disability was prepared, and its reliability and validity verified. The
      survey was conducted on 72 patients with TBI by the caregiver of each patient. As
      a result, good reliability was indicated by the split-half method (coefficient of
      reliability: 0.95, obtained using Spearman-Brown correction formula). The total
      score of the questionnaire had a significant correlation with the total score of
      the simultaneously conducted Japanese version of Neuropsychiatry Inventory at the
      0.01 level (Spearman's rank correlation, 0.47). It also had a significant
      correlation with the total score of the simultaneously conducted Japanese version
      of the Dysexecutive Questionnaire at the 0.05 level (Spearman's rank correlation,
      0.36). Six factors constituting this neurobehavioral disability were extracted
      from a factor analysis of the questionnaire survey. These factors are angry
      outburst, avolition, deficits of sympathy, depressed mood, discourse deficits,
      and degradation of appearance. Each factor indicated good internal consistency
      (Cronbach alpha, 0.86-0.94). The present results indicate that this questionnaire
      has good reliability and validity, therefore it can be a significant indicator in
      TBI neurobehavioral disability study.

PMID- 18081629
TI  - Effectiveness of comprehensive supports for schizophrenic women during pregnancy
      and puerperium: preliminary study.
AB  - The risks of deteriorated psychiatric symptoms/daily life functioning should be
      warned of in schizophrenic women during pregnancy and puerperium. The purpose of
      the present paper was to prospectively monitor mental status and functioning of
      pregnant women with schizophrenia, and investigate the effects of various
      supports. Subjects were 20 schizophrenic women who visited a clinic providing
      care and support for pregnant women with psychiatric diseases, consisting of 12
      patients with psychotic deterioration (deterioration group) and eight remitted
      stable patients (stable group). Psychiatric assessments were performed using
      Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning
      (GAF) at three time-points: at the first examination, after fixed prescription
      during pregnancy, and after delivery. The types/doses of drugs and other non-drug
      related supports (13 items) were recorded during the study period. Although a
      higher total PANSS score at the first examination (P = 0.004) and lower GAF
      scores at the first examination and even after fixed prescription (P = 0.0003)
      were observed in the deterioration group, those after delivery finally caught up
      with the levels in the stable group. Doses of antipsychotic drugs were gradually
      increased in the deterioration group although no significant differences in
      chlorpromazine equivalent doses were found between the two groups after fixed
      prescription. There was a positive correlation between the number of non-drug
      related supports and amelioration score in PANSS (r(s) = 0.553, P = 0.012). These
      findings suggest that comprehensive intervention is a requisite in pregnant
      schizophrenic women, especially with psychotic deterioration, and that non-drug
      related supports may also contribute to maintenance of good and stable mental
      status in these patients.

PMID- 18081630
TI  - Two dimensions of anosognosia in patients with Alzheimer's disease: reliability
      and validity of the Japanese version of the Anosognosia Questionnaire for
      Dementia (AQ-D).
AB  - Although a number of studies have examined anosognosia of cognitive deficits in
      patients with Alzheimer's disease (AD), not much is known about the anosognosia
      of behavioral symptoms in AD. The aims of the present study were to establish a
      Japanese version of the Anosognosia Questionnaire-Dementia (AQ-D) and to examine
      its factor structure, reliability and validity, and to identify the effects of
      various variables on the AQ-D. Factor structure, internal consistency, test
      retest reliability and concurrent validity of the Japanese version of the AQ-D
      were analyzed. Multiple regression was then done using the results of the AQ-D as
      dependent variables and entering all relevant predictor variables. Both the
      internal consistency and the test-retest reliability of the AQ-D were excellent.
      Factor analysis indicated four factors: anosognosia of basic and instrumental
      activities of daily living; that of episodic memory and orientation; that of
      disinhibited behaviors; and that of apathy and depression. The first two factors
      were regarded as anosognosia of cognitive deficits and were associated with Mini
      Mental State Examination scores, while the latter two factors were regarded as
      anosognosia of behavioral symptoms and were associated with the Neuropsychiatric
      Inventory (NPI) score. A dissociation between the two domains of anosognosia was
      confirmed, namely of cognitive deficits and of behavioral symptoms using the
      Japanese version of the AQ-D. The knowledge that various factors may have
      different effects on different domains of anosognosia in patients with AD may
      serve as useful information for clinicians assessing anosognosia in AD.

PMID- 18081631
TI  - Panic symptoms in schizophrenia: comorbidity and clinical correlates.
AB  - The aim of the present study was to investigate the prevalence of panic attack
      (PA) and panic disorder (PD) in patients with schizophrenia and detect the
      clinical features. Forty-nine patients with schizophrenia were included in the
      study. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating
      Scale (HDRS), Clinical Global Impression (CGI), Extrapyramidal Symptom Rating
      Scale (ESRS) and Bandelow Panic and Agoraphobia Rating Scale were administered.
      Fifteen patients were found to have PA and seven patients had PD. Patients with
      panic symptoms had higher scores of PANSS, HDRS, CGI and ESRS. Comorbid panic
      symptoms in schizophrenia may be related to positive symptoms, extrapyramidal
      side-effects and depression.

PMID- 18081632
TI  - Dexamethasone suppression test in borderline personality disorder: impact of PTSD
      symptoms.
AB  - The purpose of the present study was to investigate the impact of post-traumatic
      stress disorder (PTSD) symptoms on hypothalamic-pituitary-adrenal axis feedback
      regulation in 18 female patients with borderline personality disorder (BPD) and
      21 healthy controls. Reduced feedback sensitivity was found in BPD patients with
      a low number of PTSD symptoms, while findings in the BPD group with a high number
      of PTSD symptoms did not differ from those in controls. The results suggest a
      hypo-suppression in the dexamethasone suppression test in BPD with few PTSD
      symptoms.

PMID- 18081633
TI  - Comparison of developmental/intellectual changes between autistic disorder and
      pervasive developmental disorder not otherwise specified in preschool years.
AB  - This study is the first to compare the change in developmental quotient (DQ) or
      IQ between autistic disorder (AD) and pervasive developmental disorder not
      otherwise specified (PDDNOS) in preschool years. Forty-nine AD children and 77
      PDDNOS children were evaluated at age 2 and at age > or =5. The AD children were
      significantly lower in DQ/IQ at initial evaluation and outcome evaluation (also
      with initial DQ being controlled for) than the PDDNOS children.

PMID- 18081634
TI  - Increased positive thought disorder with illness duration in patients with
      schizophrenia.
AB  - It is unclear whether the severity of positive formal thought disorder, a core
      clinical feature of schizophrenia, is stable or worsening through the chronic
      course of the illness. The neurocognitive basis for positive thought disorder
      also remains unclear. The aim of the present paper was to examine the
      relationship between thought disorder as measured by the Thought Disorder Index
      (TDI) and duration of illness and neuropsychological indices in 79 patients with
      schizophrenia. TDI scores increased in proportion to illness duration. TDI scores
      were not associated with verbal memory or executive functioning. These results
      indicate an ongoing worsening of positive thought disorder through the course of
      illness in schizophrenia.

PMID- 18081635
TI  - Methamphetamine psychosis in which tardive dystonia was successfully treated with
      clonazepam.
AB  - Reported herein is a case of methamphetamine psychosis in which tardive dystonia
      was treated successfully with clonazepam. The patient was a 69-year-old man who
      had taken methamphetamine habitually for approximately 40 years. Auditory
      hallucinations had developed 25 years previously, for which haloperidol had been
      prescribed. Tardive dystonia had developed in December 2005. Haloperidol was
      withdrawn and risperidone or olanzapine alone had been administered, but neither
      had improved the dystonic posture. However, when clonazepam was added, a gradual
      improvement in the dystonic posture became evident. Tardive dystonia is currently
      treated on a trial-and-error basis. Accumulation of further cases similar to the
      present one is very important for establishing an effective treatment.

PMID- 18081636
TI  - Effectiveness of carbamazepine for benzodiazepine-resistant impulsive aggression
      in a patient with frontal infarctions.
AB  - Anticonvulsants have been used for the treatment of impulsive aggression since
      the 1980s. A 50-year-old man suffered from irritability and agitation after
      developing a right ipsilateral frontal lobe infarction as a result of Moyamoya
      disease; these symptoms caused difficulties with his working and interpersonal
      relationships. The patient had been treated using multiple benzodiazepine agents
      for 2 years but his symptoms had not improved. However, after treatment with
      carbamazepine (CBZ; 200 mg) was begun, the patient's irritability and agitation
      gradually decreased. The efficacy of CBZ treatment in this patient suggests a
      method for controlling benzodiazepine-resistant impulsive aggression.

PMID- 18081637
TI  - Onset of multiple sclerosis following post-partum depressive and manic episodes.

PMID- 18081638
TI  - Olanzapine monotherapy for late-onset vocal tics in a schizophrenic patient.

PMID- 18081639
TI  - Successful treatment of Meige's syndrome induced by risperidone and fluvoxamine
      with olanzapine monotherapy in schizophrenia.

PMID- 18081640
TI  - Proposals for suicide prevention in general hospitals in Japan.

PMID- 18081642
TI  - Review article: The endoscopic treatment of gastro-oesophageal reflux disease.
AB  - BACKGROUND: Over the last 10 years a number of endoscopic procedures for treating
      gastro-oesophageal reflux disease (GORD) have been developed (suturing,
      injections, implants and radiofrequency ablation), thus obviating the need for
      long-term proton pump inhibitors (PPI) and the potential morbidity of
      laparoscopic fundoplication. AIM: To present an update of the literature studying
      the clinical efficacy of endoscopic antireflux procedures, and to discuss further
      developments. METHODS: A PubMed search was performed for endoscopic suturing,
      antireflux treatment, endoscopic gastroplication, polymer injection,
      radiofrequency ablation of GORD. Own recent research was compared with existing
      data. Information concerning GORD endotherapy were gathered. RESULTS:
      Uncontrolled studies have reported promising clinical results on the short to
      intermediate term for most endoscopic GORD procedures, but the placebo effect
      remained unknown. It is, therefore, commendable that the three main procedures
      (Endocinch, Stretta and Enteryx) have now all been tested against a sham
      procedure. Although all three techniques were able to improve symptoms, quality
      of life and PPI use, oesophageal acid reduction was unremarkable. Endocinch and
      Stretta are safe outpatient procedures. Concerns about the durability of
      Endocinch have risen. Polymer injection (Enteryx) and gel prosthesis implantation
      (Gatekeeper) were recalled for severe complications and lack of efficacy,
      respectively. CONCLUSIONS: Endotherapy has shown the potential to treat
      (uncomplicated) GORD. However, some early procedures have failed or proven
      unsafe. Further developments and studies are necessary to determine what
      modifications to these techniques are required to produce optimal efficacy and
      durability. Until then, widespread clinical use of endotherapy for GORD should
      probably be avoided.

PMID- 18081643
TI  - Review article: The measurement of non-acid gastro-oesophageal reflux.
AB  - BACKGROUND: Oesophageal pH monitoring has been used for three decades to study
      gastro-oesophageal reflux, but it does not allow detection of non-acid reflux
      episodes. AIM: To discuss the techniques by which non-acid reflux can be measured
      and to evaluate the clinical relevance of such measurements. METHODS: Review of
      the literature on non-acid reflux monitoring. RESULTS: Ambulatory oesophageal
      impedance monitoring (using a catheter with ring electrodes) allows one to detect
      all types of gastro-oesophageal reflux, acid as well as non-acid. Measurement of
      intra-oesophageal bilirubin concentration also detects reflux irrespective of the
      pH, but only when there is bilirubin in the gastric juice and technical short
      comings limit the applicability of this technique. In untreated subjects, about
      50% of reflux episodes are non-acid (nadir pH > 4). In patients on acid
      inhibition, up to 95% of reflux episodes are non-acid. Treatment with an acid
      inhibitor leads to a significant decrease in the incidence of acid reflux
      episodes, but not to a reduction in the total number of reflux episodes. This
      shift is associated with a shift in symptoms from heartburn to regurgitation.
      With impedance monitoring, the temporal association between symptoms that persist
      during inhibition of acid secretion and non-acid reflux events can be
      demonstrated. In a proportion of patients with chronic cough, the coughing
      episodes are preceded by non-acid reflux. CONCLUSIONS: Intraluminal impedance
      monitoring of gastro-oesophageal reflux is a feasible technique, which provides
      clinically important information about the relationships between symptoms and non
      acid reflux events.

PMID- 18081644
TI  - Review article: Gastro-oesophageal reflux disease--application of the concept of
      complete remission.
AB  - BACKGROUND: Therapeutic success in the treatment of gastro-oesophageal reflux
      disease cannot be measured by endoscopic healing or symptomatic relief alone.
      Assessment of treatment efficacy should be based on symptomatic relief and
      endoscopic healing. As most questionnaires focus on heartburn, it is important to
      stress that there is more to gastro-oesophageal reflux disease than just
      heartburn. The 'complete remission' concept was recently introduced; an approach
      in which endoscopic appearances and symptomatic relief are integrated, thus
      allowing the full gastro-oesophageal reflux disease picture and its changes over
      time to be described in a simple and accurate manner. Complete remission is
      defined as the absence of both oesophagitis and symptoms. ReQuest, a relatively
      new questionnaire acceptable as a clinical endpoint in trials, seems to be of use
      in daily practice. AIM: To review the utility of the ReQuest questionnaire.
      RESULTS: This questionnaire assesses the gastro-oesophageal reflux disease
      symptom profile using 67 symptom descriptions adapted from patients' view,
      doctors' view, clinical trials and from the literature. Individual symptoms are
      reduced to seven dimensions by factor analysis and expert consensus. This gives
      insight into multiple symptoms over time as well as individual patient profiles.
      ReQuest determines symptom relief using a gastro-oesophageal reflux disease
      symptom threshold. This unique concept allows the doctor to measure the time to
      first symptom relief and also to sustained symptom relief. CONCLUSIONS: ReQuest
      makes it possible to evaluate the complete symptom spectrum in patients with non
      erosive oesophageal reflux disease and gastro-oesophageal reflux disease. ReQuest
      is available for daily practice to use for comparability with regard to treatment
      efficacy.

PMID- 18081645
TI  - Review article: The laryngological manifestations of reflux disease; why the
      scepticism?
AB  - BACKGROUND: Despite increasing clinical and experimental evidence of its
      existence, otolaryngological manifestations of reflux disease remain
      controversial, concerning diagnosis as well as treatment. AIM: Proper
      understanding of laryngopharyngeal reflux disease (LPRD). METHOD: Review of
      literature. RESULTS: Scepticism concerning LPRD is based upon differences between
      gastro-oesophageal reflux disease and LPRD; lack of specificity and sensitivity
      of diagnostic tests to confirm LPRD; non-specificity of laryngological symptoms,
      which are difficult to distinguish from other causes of upper respiratory tract
      inflammation; non-specificity of laryngological signs in laryngoscopy, with high
      intra- and inter-observer variability in evaluation; diagnosis of LPRD is
      essentially only based on a combination of diagnostic signs and symptoms, which
      cannot be attributed to other pathology; slow, or sometimes lack of, response of
      LPRD symptoms to proton pump inhibitor (PPI) medication and lack of evidence
      concerning efficacy of PPIs in placebo-controlled trials. CONCLUSIONS: LPRD
      remains a diagnosis by exclusion and resolution of symptoms following 4-month
      trial of 40 mg PPI twice daily is, for all practical purposes, considered proof
      of the initial diagnosis. However, non-response does not exclude LPRD as PPIs
      have no influence on noxious non-acid components of the refluxate.

PMID- 18081646
TI  - Review article: Helicobacter pylori eradication for the prevention of gastric
      cancer.
AB  - BACKGROUND: Gastric cancer is the fourth most common cancer and second leading
      cause of cancer-related death worldwide. A clear association between Helicobacter
      pylori infection and gastric cancer was established years ago. H. pylori
      eradication may be an effective approach to decrease morbidity and mortality of
      gastric cancer. AIM: To discuss current evidence of H. pylori eradication for
      prevention of gastric cancer. RESULTS: Recent studies have shown that the
      association between H. pylori and gastric cancer has probably been
      underestimated. This may have resulted from negative H. pylori status in subjects
      after loss of colonisation in the presence of atrophic gastritis and intestinal
      metaplasia, prior to development of gastric cancer. The recognition of the
      central role of H. pylori in carcinogenesis has increased expectations of gastric
      cancer prevention by H. pylori eradication. A primary preventive effect of
      eradication in subjects with H. pylori-induced gastritis has been demonstrated.
      However, a secondary preventive effect in patients with pre-malignant gastric
      lesions is still controversial, especially in patients with intestinal metaplasia
      and dysplasia. CONCLUSIONS: At this moment, H. pylori eradication seems indicated
      at the earliest stage of gastric carcinogenesis. This treatment policy requires
      confirmation; results of ongoing randomised controlled trials are therefore
      eagerly awaited.

PMID- 18081647
TI  - Review article: The diagnosis and management of gastroparesis.
AB  - BACKGROUND: Gastroparesis is a disorder characterized by a delay in gastric
      emptying of a meal in the absence of a mechanical gastric outlet obstruction.
      AIM: To provide an evidence based overview on diagnosis and management of
      gastroparesis. METHODS: A PubMed search was performed using search terms
      including gastroparesis, gastric retention, gastric emptying, accommodation,
      manometry, prokinetics, antiemetics, metoclopramide, domperidone, erythromycin,
      botulinum toxin, gastric pacing. Relevant studies were identified and original
      articles and reviews were collected. References in these articles were examined
      for relevance and included where appropriate. RESULTS: Diagnosis of gastroparesis
      is based on the presence of symptoms such as nausea, vomiting and postprandial
      abdominal fullness and on an objectively determined delay in gastric emptying.
      The true prevalence of gastroparesis is unknown. Gastric emptying can be assessed
      by scintigraphy and stable isotope breath tests. Management of gastroparesis
      consists of dietary and lifestyle measures and/or pharmacological interventions
      (prokinetics, antiemetics, intrapyloric botulinum toxin injection) or other
      interventions that focus on adequate nutrient intake either through a
      nasoduodenal tube, percutaneous gastrostomy or jejunostomy. CONCLUSIONS: Accurate
      diagnosis of gastroparesis requires an adequate protocol to measure gastric
      emptying. Treatment options in gastroparesis remain limited despite the disabling
      nature of the disorder.

PMID- 18081648
TI  - Review article: The relevance of surveillance endoscopy in long-lasting
      inflammatory bowel disease.
AB  - BACKGROUND: Development of colitis-associated colorectal cancer is an important
      clinical problem in patients with colonic inflammatory bowel disease (IBD).
      British and American guidelines recommend to start surveillance after a disease
      duration of 8-10 or 15-20 years for patients with extensive or left-sided
      colitis, respectively. AIM: To assess the evidence level of current surveillance
      strategies. METHODS: A PubMed-based literature search using the search terms
      inflammatory bowel disease, ulcerative colitis, Crohn's disease, dysplasia,
      colorectal cancer and surveillance was performed. RESULTS: Low-grade and high
      grade dysplastic lesions progress to cancer in a high percentage of patients.
      Furthermore, concurrent cancer is found in approximately one-third of the
      patients with colonic dysplasia. Low-level evidence showing reduced colorectal
      cancer-related mortality in patients who were undergoing surveillance is
      available. Patients with concomitant primary sclerosing cholangitis form a
      subgroup of IBD patients with an even higher risk of colorectal neoplasia.
      CONCLUSIONS: Colonic surveillance prolongs life expectancy of patients with long
      lasting IBD.

PMID- 18081649
TI  - Review article: The clinical importance of growth in children with inflammatory
      bowel disease: is it important to the gastroenterologist?
AB  - BACKGROUND: Growth in children with inflammatory bowel disease is often
      compromised. AIM: To explore the origins of growth retardation in paediatric
      inflammatory bowel disease and to consider management strategies. METHODS:
      Relevant literature was identified and reviewed. RESULTS: A combination of the
      following factors results in growth retardation: insufficient food intake,
      malabsorption, increased catabolism, disease activity, disease extension,
      complications of disease and the side-effects of treatment. CONCLUSIONS: Failure
      of normal growth in a child with inflammatory bowel disease is an indicator of
      insufficient and unsuccessful therapy. The major causative factor is chronic
      anorexia because of chronic catabolic illness. Growth resumes to normal after
      effective control of the disease and nutritional intake. Regular follow-up of
      growth in these children is mandatory, and the measurement of both height and
      weight is an ideal indication of effective treatment. Failure of sustained growth
      in a child or adolescent with inflammatory bowel disease is a warning to consider
      a change of clinical strategy.

PMID- 18081650
TI  - Review article: Inflammatory bowel disease and genetics.
AB  - INTRODUCTION: Inflammatory bowel disease (IBD) comprising ulcerative colitis (UC)
      and Crohn's disease (CD) is multigenic disorder. Tremendous progress has been
      achieved in unravelling the genetic background of IBD. It has led to the
      discovery of mutations in NOD2 associated with ileal CD and numerous other genes
      have been found to be associated with IBD susceptibility. METHODS: A review of
      the literature on the genetic background of IBD was performed. RESULTS: It is
      only partially understood how mutations in NOD2 lead to CD. Mouse models, in
      vitro data and studies in humans offer conflicting data as regards whether there
      is a loss or gain of function of NOD2 in CD. Several additional genes have been
      identified of which only a few are currently being recognized as potential
      disease causing or disease modifying genes. Promising candidate genes include
      TLR4, MDR1, NOD1 (CARD4), DLG5 as well as the IBD5 locus including SLC22A4/5.
      CONCLUSIONS: Although genetic research has not yet led to a better prediction of
      the disease course or patient selection for medical therapy, remarkable progress
      has been made in the understanding of the pathogenesis of IBD. For future genetic
      research, accurate phenotyping of patients is very important and large population
      based cohorts are needed. Eventually, genetic research may be able to classify
      different disease phenotypes on a more detailed molecular basis and may provide
      important contributions in the development of new therapeutic approaches.

PMID- 18081651
TI  - Review article: Management of diverticulitis.
AB  - BACKGROUND AND AIM: The incidence and therefore complications of (sigmoid)
      diverticular disease are increasing. METHODS: Review of current literature.
      RESULTS: From all patients, 15% will develop diverticulitis, 5% complications and
      5% diverticular bleeding. Diagnosis is established with computerised tomography.
      Colonoscopy is needed to rule out malignancy. NSAIDs increase the risk of
      perforation; steroids, diabetes, collagen vascular disease and immune compromised
      are associated with complicated disease and death. In mild diverticulitis,
      antibiotics are recommended. In complicated disease with abscesses, <5 cm
      antibiotics are sufficient. Larger abscesses are drained under computerised
      tomography-guidance. Peritonitis forms an indication for surgery. Diverticulitis
      recurrence rate is around 30%, most are uncomplicated. Recurrence after surgery
      is around 10%. Elective surgery is reserved for fistula closure and obstruction.
      The need for elective surgery to prevent recurrence has diminished because of new
      insights. Important is to identify risk groups. New issues are the possible
      relationship between diverticulitis and cancer, segmental colitis associated with
      diverticulitis, and treatment of diverticulitis with mesalazine and probiotics.
      CONCLUSIONS: Uncomplicated diverticulitis is treated medically. Complicated
      diverticulitis with small abscesses is treated with antibiotics while larger
      abscesses are drained with computerised tomography-guided puncture. Emergency
      surgery is reserved for peritonitis, elective surgery for fistula/stenosis.
      Surgery to prevent recurrence is indicated only in selected cases (e.g. immune
      compromised).

PMID- 18081652
TI  - Review article: Stem cell transplantation for the treatment of gastrointestinal
      diseases--current applications and future perspectives.
AB  - BACKGROUND: Haematopoietic stem cell transplantation (HSCT) can be used to cure
      or ameliorate a variety of non-malignant diseases. These range from inherent
      defects of haematopoiesis, through metabolic diseases, to severe autoimmune
      diseases. The rationale for this strategy is based on the concept of
      immunoablation using high-dose chemotherapy, with subsequent regeneration of
      naive T-lymphocytes derived from reinfused haematopoietic progenitor cells.
      Possibly the use of SCT allows the administration of high-dose chemotherapy
      resulting in a prompt remission in these therapy-refractory patients. AIM: This
      review highlights the major scientific developments and defines the areas of
      successful use of HSCT in gastrointestinal disorders and gives a perspective on
      possible future applications. METHODS: A search in the Medline has been conducted
      and all relevant published data were analysed. RESULTS: HSCT has been proved
      successful in treating refractory Crohn's disease. A selected group of refractory
      coeliac patients having a high risk of developing enteropathy associated T-cell
      lymphoma has been recently treated with promising results. In cryptogenic
      cirrhosis, basic research and unpublished data concerning mesenchymal SCT are
      encouraging. CONCLUSION: In refractory autoimmune gastrointestinal diseases, it
      seems that high-dose chemotherapy followed by HSCT is feasible and safe and might
      result in long-term improvement of disease activity.

PMID- 18081653
TI  - Review article: New developments in colonic imaging.
AB  - BACKGROUND: Colonoscopic detection and removal of neoplasia from the colorectum
      prevent the development of colorectal cancer. Sporadic adenomas and neoplasia
      associated with ulcerative colitis are frequently missed during colonoscopy, as a
      result of which, interval cancers might develop. AIM: To review new developments
      in colonoscopic imaging concerning the detection of neoplasia. METHODS: Medical
      databases were searched for relevant publications, dealing with advanced
      endoscopic imaging techniques during colonoscopy. RESULTS: Pancolonic
      chromoendoscopy has shown to increase the detection of sporadic adenomas and
      ulcerative colitis associated neoplasia, at the expense of longer examination
      times. As chromoendoscopy is labour intensive and time-consuming, its widespread
      use has been hampered. Narrow band imaging is a novel endoscopic imaging
      technique, which enhances mucosal and vascular details. Recent studies indicate
      that narrow band imaging has a high yield for neoplasia; however, no improvement
      compared to standard colonoscopy has been demonstrated. Autofluorescence imaging
      is another new technique for which blue endoscopic light is used to induce
      mucosal autofluorescence. So far, preliminary results have shown promising
      results of autofluorescence imaging for neoplasia detection. CONCLUSION: Whether
      chromoendoscopy or novel advanced imaging techniques will change current
      colonoscopic practice depends on results of future studies comparing these
      different colonoscopic techniques.

PMID- 18081654
TI  - Review article: Detection and management of hereditary non-polyposis colorectal
      cancer (Lynch syndrome).
AB  - BACKGROUND: The most common hereditary colorectal cancer syndrome is hereditary
      non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome. Diagnosis
      of this syndrome is difficult, because of lack of specific diagnostic features.
      AIM: To discuss the diagnostic criteria and laboratory work up for HNPCC.
      Furthermore, surveillance programs for HNPCC and treatment of HNPCC associated
      colorectal cancer are discussed. RESULTS: Current diagnostic criteria, including
      the Amsterdam II and Bethesda criteria, are suboptimal for the detection of
      HNPCC. Molecular screening by microsatellite instability (MSI) and
      immunohistochemistry (IHC) is useful in the diagnosis of HNPCC. Both techniques
      have a higher sensitivity compared to the Amsterdam II and Bethesda criteria. A
      combination of both MSI and IHC provides the most optimal selection for mutation
      analysis. After identification of a mutation in an affected individual, genetic
      counselling and presymptomatic mutation analysis should be offered to relatives.
      Furthermore, colonoscopic surveillance should be performed in proven mutation
      carriers. CONCLUSIONS: Identification of HNPCC is a clinical challenge involving
      many clinicians. Identification of persons at risk can be achieved by a
      combination of a detailed family history, testing with molecular and mutation
      analysis.

PMID- 18081655
TI  - Review article: The Lynch syndrome (hereditary nonpolyposis colorectal cancer).
AB  - BACKGROUND: The most common inherited colorectal cancer syndrome is the Lynch
      syndrome (HNPCC) which is characterized by the development of colorectal,
      endometrial, and other cancers and the presence of microsatellite instability
      (MSI) in tumours. The syndrome is due to a mutation in one of the mismatch repair
      (MMR) genes: MSH2, MLH1, MSH6 and PMS2. AIMS: To evaluate the clinical features
      of the Lynch syndrome and to assess the tools that are available for the
      identification of families with this syndrome. METHODS: A systematic literature
      search using PubMed and reference lists of retrieved articles was performed.
      RESULTS: The review provides an update of the clinical phenotype of the Lynch
      syndrome. Until recently, the Amsterdam criteria were the most important tool for
      the identification of Lynch syndrome. Nowadays, the Bethesda guidelines are more
      widely used. These guidelines describe all clinical conditions in which a search
      for MSI indicated. Both MSI-analysis as well as immunohistochemical analysis of
      the MMR-proteins are appropriate to identify patients with a high probability of
      carrying a MMR-gene mutation. CONCLUSION: All specialists that are involved in
      the treatment of cancer patients should know the Bethesda criteria in order to
      identify all families suspected of the Lynch syndrome.

PMID- 18081656
TI  - Original article: New surgical approaches to the Klatskin tumour.
AB  - BACKGROUND: Surgical treatment of hilar cholangiocarcinoma (Klatskin tumours) is
      difficult because of its central location in the liver hilum. Recent developments
      in surgical techniques have improved the outcome after resection. AIM: To
      describe the surgical approaches currently applied in our centre and the impact
      of these strategies on outcome and criteria for resection. METHODS: From 1988 to
      2003, 99 consecutive patients underwent resection for hilar cholangiocarcinoma.
      Patients were analysed for rate of R0 resections in relation with Bismuth
      classification. Morbidity, mortality and survival were assessed. RESULTS: The
      rate of hilar resections in combination with (extended) liver resections for type
      III and IV tumours increased from 24% to 95% in the last 5 years of the study
      period. Eight patients (8%) had Bismuth type IV tumours. Four of these patients
      underwent palliative local excisions of the hepatic duct confluence whereas the
      other four patients underwent hilar resection in combination with partial liver
      resection, resulting in microscopically radical resections. There was no
      mortality in this group. Overall postoperative morbidity and mortality were 68%
      and 10%, respectively. CONCLUSIONS: An aggressive surgical approach consisting of
      hilar resections combined with partial liver resections including segments 1 and
      4, resulted in a higher rate of R0 resections. Even Bismuth type IV tumours may
      be resectable depending on the biliary anatomy of the hepatic duct confluence.

PMID- 18081657
TI  - Review article: Probiotics in gastrointestinal and liver diseases.
AB  - BACKGROUND: Probiotics, defined as live micro-organisms with beneficial effects
      for the host, are widely applied in gastrointestinal and liver diseases. AIM AND
      METHOD: To review the available evidence of clinical trials on probiotics in
      gastrointestinal and liver diseases, with a major focus on irritable bowel
      syndrome, inflammatory bowel disease, pancreatitis and chronic liver diseases.
      RESULTS: Evidence for the therapeutic or preventive application of particular
      probiotic strains is available for antibiotic-associated diarrhoea, rota-virus
      associated diarrhoea and pouchitis. Results are encouraging for irritable bowel
      syndrome, ulcerative colitis and for reducing side effects by Helicobacter pylori
      eradication therapies, but are less clear for Crohn's disease, lactose
      intolerance and constipation. In general, for most of these patient groups, more
      placebo-controlled methodologically well-designed studies that pay attention to
      both clinical outcome and mechanistic aspects are required. The application in
      liver disease and pancreatitis is promising, but more human trials have to be
      awaited. Possible mechanisms of probiotics include modulation of the intestinal
      microbiota and the immune system, but different bacterial may have different
      effects. CONCLUSION: Further insight into disease entities and the functioning of
      probiotic strains is required to be able to select disease-specific strains,
      which have to be tested in well-designed placebo-controlled studies.

PMID- 18081658
TI  - Review article: The function and regulation of proteins involved in bile salt
      biosynthesis and transport.
AB  - BACKGROUND: Bile salts are produced and secreted by the liver and are required
      for intestinal absorption of fatty food components and excretion of endobiotics
      and xenobiotics. They are reabsorbed in the terminal ileum and transported back
      to the liver via the portal tract. Dedicated bile salt transporters in
      hepatocytes and enterocytes are responsible for the unidirectional transport of
      bile salts in the enterohepatic cycle. AIM: To give an overview of the function
      and regulations of proteins involved in bile salt synthesis and transport.
      METHODS: Data presented are obtained from PubMed-accessible literature combined
      with our own recent research. RESULT: Hepatocytes and enterocytes contain unique
      bile salt importers (sodium-taurocholate cotransporting polypeptide and apical
      sodium-dependent bile acid transporter, respectively) and exporters (bile salt
      export pump and organic solute transporter alpha-beta, respectively). Enzymes
      involved in bile salt biosynthesis reside in different subcellular locations,
      including the endoplasmic reticulum, mitochondria, cytosol and peroxisomes.
      Defective expression or function of the transporters or enzymes may lead to
      cholastasis. The bile salt-activated transcription factor Farnesoid X receptor
      controls expression of genes involved in bile salt biosynthesis and transport.
      CONCLUSIONS: Detailed knowledge is available about the enzymes and transporters
      involved in bile salt homeostasis and how their defective function is associated
      with cholestasis. In contrast, the process of intracellular bile salt transport
      is largely unexplored.

PMID- 18081659
TI  - Review article: Multimodality treatment of liver metastases increases suitability
      for surgical treatment.
AB  - BACKGROUND: Liver metastases of colorectal cancer occur frequently, but only 10
      20% are eligible for liver surgery. Recent new developments changed the concepts
      of treating patients with colorectal liver metastases. AIM: To describe the
      available modalities that can result in increasing resectability rate. METHODS:
      Potentials and drawbacks of portal vein embolization, radiofrequency ablation
      (RFA), trans-ablated tumour hepatectomy, neoadjuvant chemotherapy and the
      approach to patients with extrahepatic metastases are described. RESULTS: Portal
      vein embolization is a well-established technique to increase the volume of the
      future liver remnant. RFA should be applied if partial liver resection alone
      cannot make the liver tumour-free. Neoadjuvant chemotherapy in patients with
      unresectable liver metastases can result in secondary resectability rates of 15
      40%. Hepatotoxicity can lead to a higher complication rate after partial liver
      resection. A limited number of extrahepatic tumour localizations should be
      resected as well. CONCLUSIONS: A more aggressive approach to patients with
      colorectal liver metastases improves resectability rate and survival.
      Unfortunately, these new options have not been thoroughly evaluated in randomized
      controlled trials. For some of these modalities, the currently available results
      are so promising that it might be difficult to start such trials in the future.

PMID- 18081660
TI  - Review article: Success and failure of nucleoside and nucleotide analogues in
      chronic hepatitis B.
AB  - BACKGROUND: Strong suppression of viral replication and normalization of alanine
      aminotransferase is feasible with nucleos(t)ide analogues. It is estimated viral
      replication and liver inflammation can be controlled in 90% of patients with
      chronic hepatitis B with the current available treatments. AIM: To review the
      studies currently available on the management of chronic hepatitis B with
      nucleos(t)ide analogues. RESULTS: Although very potent, nucleos(t)ide analogues
      are not effective in every patient. Some factors are known to influence treatment
      outcome, but many host and viral factors are still unknown. Stopping rules have
      to be defined to assess treatment efficacy in an early stage and change the
      regimen. Discontinuation of nucleos(t)ide analogues is often followed by
      reactivation of HBV. Data on the risk factors for relapse are necessary in order
      to decide if treatment can be safely discontinued. Another major drawback of
      nucleos(t)ide analogues is the emergence of resistance. The efficacy of compounds
      for the treatment of mutant virus and the impact of cross-resistance is largely
      unknown. The use of combination therapy to prevent resistance looks promising,
      but has to be proven. CONCLUSIONS: HBV has become a treatable disease, however
      much research is needed to optimize treatment for individual patients and
      treatment failures.

PMID- 18081661
TI  - Review article: Management of ascites and associated complications in patients
      with cirrhosis.
AB  - BACKGROUND: Ascites is the most common complication of cirrhosis, associated with
      an expected survival below 50% after 5 years. Prognosis is particularly poor for
      patients with refractory ascites and for those developing complications,
      including spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS).
      AIM: To provide an evidence-based overview of the pathophysiology, diagnosis and
      clinical management of ascites secondary to liver cirrhosis. METHODS: Review
      based on relevant medical literature. RESULTS: Portal hypertension, splanchnic
      vasodilatation and renal sodium retention are fundamental in the pathophysiology
      of ascites formation. The SAAG (serum-ascites albumin gradient) allows reliable
      assessment of the cause of ascites. The majority of cirrhotic patients with
      ascites can be managed with dietary sodium restriction in combination with
      diuretic agents. Large volume paracentesis with albumin suppletion and TIPS are
      therapeutic options in patients with refractory ascites. Prophylactic antibiotics
      for SBP should be given in certain patient populations. CONCLUSIONS: Recent
      advances in the diagnosis and treatment of ascites and associated complications
      have improved the medical management and poor prognosis of patients with these
      manifestations of advanced liver disease. Early diagnosis, adequate treatment and
      focus on prevention of complications remain essential as well as timely referral
      for liver transplantation.

PMID- 18081662
TI  - Review article: Non-alcoholic fatty liver disease in morbidly obese patients and
      the effect of bariatric surgery.
AB  - BACKGROUND: Morbid obesity is strongly associated with non-alcoholic fatty liver
      disease. The effects of bariatric surgery on liver tests an histological
      abnormalities after weight loss are controversial. AIM: To review the literature
      on the prevalence of non-alcoholic fatty liver disease in patients with morbid
      obesity with respect to laboratory and histopathological parameters and the
      effect of weight loss on these parameters after bariatric surgery. RESULTS:
      Standard liver tests do not seem to be a sensitive tool for the assessment and
      follow-up of non-alcoholic fatty liver disease in obesity. In nearly all patients
      with morbid obesity, histological abnormalities reflecting non-alcoholic fatty
      liver disease are present. Bariatric surgery in these patients will decrease the
      grade of steatosis. However, there are some concerns about the effect of
      bariatric surgery on hepatic inflammation and fibrosis. In particular, older
      follow-up studies reported negative results as opposed to more recent studies,
      which also showed improvement in hepatic inflammation and fibrosis.
      Unfortunately, most studies had limitations because of the selection of patients.
      CONCLUSION: Despite limitations in many studies, bariatric surgery seems to be a
      promising treatment in patients with obesity presenting with non-alcoholic fatty
      liver disease.

PMID- 18081663
TI  - Review article: The management of non-cirrhotic non-malignant portal vein
      thrombosis and concurrent portal hypertension in adults.
AB  - BACKGROUND: Extrahepatic portal vein thrombosis is an important cause of non
      cirrhotic portal hypertension. AIM: To provide an update on recent advances in
      the aetiology and management of acute and chronic non-cirrhotic non-malignant
      extrahepatic portal vein thrombosis. METHOD: A PubMed search was performed to
      identify relevant literature using search terms including 'portal vein
      thrombosis', 'variceal bleeding' and 'portal biliopathy'. RESULTS:
      Myeloproliferative disease is the most common risk factor in patients with non
      cirrhotic non-malignant extrahepatic portal vein thrombosis. Anticoagulation
      therapy for at least 3 months is indicated in patients with acute extrahepatic
      portal vein thrombosis. However, in patients with extrahepatic portal vein
      thrombosis due to a prothrombotic disorder, permanent anticoagulation therapy can
      be considered. The most important complication of extrahepatic portal vein
      thrombosis is oesophagogastric variceal bleeding. Endoscopic treatment is the
      first-line treatment for variceal bleeding. In several of the patients with
      extrahepatic portal vein thrombosis biliopathy changes on endoscopic retrograde
      cholangiography (ERCP) have been reported. Dependent on the persistence of the
      biliary obstruction, treatment can vary from ERCP to hepaticojejunostomy.
      CONCLUSION: Prothrombotic disorders are the major causes of non-cirrhotic, non
      malignant extrahepatic portal vein thrombosis and anticoagulation therapy is
      warranted in these patients. The prognosis of patients with non-cirrhotic, non
      malignant extrahepatic portal vein thrombosis is good, and is not determined by
      portal hypertension complications but mainly by the underlying cause of
      thrombosis.

PMID- 18081664
TI  - Review article: The prevalence and clinical relevance of cytochrome P450
      polymorphisms.
AB  - BACKGROUND: Most drugs currently used in clinical practice are effective in only
      25% to 60% of patients, while adverse drug reactions (ADRs) as a consequence of
      treatment are estimated to cost billions of US dollars and tens of thousands of
      deaths. AIM: To review the prevalence and clinical significance of cytochrome
      P450 polymorphisms. RESULTS: The cytochrome P450 enzyme families 1-3 are
      responsible for 70 to 80% of all phase I dependent drug metabolisms. In 90%
      metabolic activity dependents on six enzymes: CYP1A2, CYP3A, CYP2C9, CYP2C19,
      CYP2D6 and CYP2E1. Polymorphisms in the CYP450 gene can influence metabolic
      activity of the subsequent enzymes. A poor metabolizer (PM) has no or very poor
      enzyme activity. A consequence of PM is drug toxicity if no other metabolic route
      is available, or when multiple drugs are metabolized by the same cytochrome. In
      that case dose reduction is an option to prevent toxic effects. CONCLUSIONS: In
      the future genotyping should be considered to identify patients who might be at
      risk of severe toxic responses, in order to guide appropriate individual dosage.
      Medical therapy should be a close cooperation between clinicians, pharmacologists
      and laboratory specialists, leading to reduced therapeutic errors, ADRs and
      health care costs.

PMID- 18081665
TI  - Review article: Surgical management of chronic pancreatitis.
AB  - BACKGROUND: The therapeutic approach to patients with chronic pancreatitis (CP)
      is complicated by the fact that patients are presented to the physician at
      different stages of disease and in the presence of varying clinical symptoms.
      Generally, an expectant approach is justified for patients with asymptomatic CP.
      At present, patients with symptoms related to gland destruction are initially
      treated by endoscopic means, while surgical treatment of CP is usually reserved
      for intractable abdominal pain, suspicion of cancer, and complications such as
      persistent pseudocysts. AIM: To review the studies currently available evaluating
      surgical and/or endoscopic management of CP. RESULTS: Improvements in imaging
      techniques, as well as a better understanding of the pathophysiology of CP and
      mechanisms causing pain, have led to a more conscious selection of patients for
      surgery. Type of surgery depends on whether the pancreatic duct is dilated,
      presence of an inflammatory mass and occurrence of complications (pseudocysts,
      gastric outlet obstruction). Eventually, after initial endoscopic treatment, a
      substantial number of patients still need surgery for persistent complaints.
      CONCLUSIONS: For patients with symptomatic CP, a multidisciplinary approach is
      indicated with low threshold to surgical intervention, since long-term pain
      relief is accomplished more often after surgical treatment than after endoscopic
      treatment.

PMID- 18081666
TI  - Review article: Translumenal endoscopic debridement of organized pancreatic
      necrosis--the first step towards natural orifice translumenal endoscopic surgery.
AB  - BACKGROUND: Over the last decades, gastrointestinal endoscopy has transformed
      from serving purely diagnostic purposes to therapeutic applications. One recent
      major progress is taking the endoscope beyond the gastrointestinal lumen into the
      peritoneal cavity for diagnostic and therapeutic procedures. The first step
      towards Natural Orifice Translumenal Endoscopic Surgery (NOTES) was translumenal
      endoscopic debridement of pancreatic necrosis. AIM: To overview current status of
      endoscopic debridement of organized pancreatic necrosis. Finally, we take a short
      look into the potential future of translumenal endoscopic procedures. METHODS:
      Medical databases were searched for relevant publications, dealing with
      endoscopic debridement of pancreatic necrosis and NOTES. RESULTS: All current
      published studies concerning endoscopic debridement of organized pancreatic
      necrosis were retrospectively performed and relatively small (largest n = 25).
      Success rates varies from 80-93% and complication rates from 7-20%. There was no
      procedure related mortality reported. Published NOTES experiments showed
      feasibility of a variety of transgastric, transcolonic and transvaginal
      procedures in the porcine model. CONCLUSION: Endoscopic debridement seems to be
      an effective and relatively safe minimally invasive therapy in patients with
      symptomatic organized pancreatic necrosis and is the first step towards NOTES.
      Further comparative studies need to define its definitive role in the management
      of these patients.

PMID- 18081667
TI  - Review article: The gastrointestinal tract: neuroendocrine regulation of satiety
      and food intake.
AB  - BACKGROUND: The gastrointestinal tract elicits numerous signals regulating food
      intake and satiety, and recently many studies have been performed to elucidate
      the mechanisms regulating these signals. AIM: To describe the effects of the
      gastrointestinal tract on satiety, satiation and food intake. METHODS: A PubMed
      search was performed to identify and select the relevant literature using search
      terms including 'gastric satiety, intestine + satiety, satiation,
      cholecystokinin, ghrelin, peptide YY, glucagon-like peptide-1 and ileal brake'.
      RESULTS: Satiation, satiety and food intake result, among other factors, from
      signals originating in the stomach caused by distension and signals from the
      small intestine. These intestinal signals result from nutrient sensing in the gut
      and activate neural and humoral pathways. Activation of the distal part of the
      gut, the so called ileal brake, leads to reduction in hunger and food intake, and
      models of chronic ileal brake activation lead to massive weight loss. CONCLUSION:
      Gastrointestinal signals are crucial for the regulation of food intake, satiety
      and satiation. The ileal brake deserves special attention, as both ileal
      intubation studies and surgical studies demonstrate that activation of the ileal
      brake reduces food intake. In the surgical models, weight loss occurs without
      adaptation to the anorectic effects of ileal brake activation.

PMID- 18081668
TI  - Two-minute mental health care for elderly patients: inside primary care visits.
AB  - OBJECTIVES: To assess how care is delivered for mental disorders using videotapes
      of office visits involving elderly patients. DESIGN: Mixed-method observational
      analysis of the nature of the topics discussed, content of discussion, and the
      time spent on mental health. SETTINGS: Three types of settings: an academic
      medical center, a managed care group, and fee-for-service solo practitioners.
      PARTICIPANTS: Thirty-five primary care physicians and 366 of their elderly
      patients. MEASUREMENTS: Videotapes of 385 visits covering 2,472 diverse topics
      were analyzed. Coding of the videotapes identified topics, determined talk time,
      and coded the dynamics of talk. RESULTS: Mental health topics occurred in 22% of
      visits, although patient survey indicated that 50% of the patients were
      depressed. A typical mental health discussion lasted approximately 2 minutes.
      Qualitative analysis suggested wide variations in physician effort in providing
      mental health care. Referrals to mental health specialists were rare even for
      severely depressed and suicidal patients. CONCLUSION: Little time is spent on
      mental health care for elderly patients despite heavy disease burdens. Standards
      of care based on a count of visits "during which a mental health problem is
      discussed" may need to be supplemented with guidelines about what should happen
      during the visit. System-level interventions are needed.

PMID- 18081669
TI  - Flu: effect of vaccine in elderly care home residents: a randomized trial.
AB  - OBJECTIVES: To determine whether assessing seroprotection after influenza vaccine
      and administering booster vaccination where not achieved reduces hospitalization
      and death. To estimate the overall seroprotection rate of influenza vaccine.
      DESIGN: A two-arm, partially blind, randomized, multicenter, parallel-group,
      controlled trial. SETTING: Twenty-six care homes in three South London boroughs
      in fall 2004. PARTICIPANTS: Two hundred seventy-seven elderly permanent care home
      residents meeting eligibility criteria. INTERVENTION: Postvaccination blood
      samples were randomized to booster evaluation or no booster evaluation (control).
      If evaluation revealed inadequate seroprotection, a booster vaccine was
      administered. MEASUREMENTS: Primary outcome was hospitalization to end April
      2005; secondary outcomes were death, antibiotic use, and seroprotection. RESULTS:
      Sixty percent of the controls and 41% of the booster evaluation group responded
      to routine vaccination. Booster vaccination where indicated increased
      seroprotection rates in the booster evaluation group to 66%. Treatment groups did
      not differ in any outcome measures in the intention-to-treat analysis
      (hospitalization odds ratio=1.02, 95% confidence interval=0.55-1.87). There was a
      tendency towards greater differences between groups in the per-protocol analysis
      than in the intention-to-treat analysis, particularly regarding seroprotection
      rates. The same effect was observed in the a priori exploratory analysis of
      residents not seroprotected after routine vaccination alone. CONCLUSION: In a
      year without circulating influenza, there is no clinical benefit of administering
      a booster vaccine if routine trivalent vaccination fails to result in
      seroprotection. Hemagglutination titers rose in two strains postbooster
      vaccination but fell against the novel strain, Wyoming. The benefit of such a
      booster strategy when influenza is prevalent thus remains uncertain.

PMID- 18081670
TI  - Indwelling device use and antibiotic resistance in nursing homes: identifying a
      high-risk group.
AB  - OBJECTIVES: To quantify the relationship between indwelling devices (urinary
      catheters, feeding tubes, and peripherally inserted central catheters) and
      carriage of antimicrobial-resistant pathogens in nursing home residents. DESIGN:
      Cross-sectional. SETTING: Community nursing home in Southeast Michigan.
      PARTICIPANTS: Residents with indwelling devices (n=100) and randomly selected
      control residents (n=100) in 14 nursing homes. MEASUREMENTS: Data on age,
      functional status, and Charlson comorbidity score were collected. Samples were
      obtained from nares, oropharynx, groin, wounds, perianal area, and enteral
      feeding tube site. Standard microbiological methods were used to identify
      methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant
      enterococci (VRE), and ceftazidime-resistant (CTZ-R) gram-negative bacteria
      (GNB). RESULTS: Use of indwelling devices was associated with colonization with
      MRSA at any site (odds ratio (OR)=2.0, P=.04), groin (OR=4.8, P=.006), and
      perianal area (OR=3.6, P=.01) and CTZ-R GNB at any site (OR=5.6, P=.003). Use of
      enteral feeding tubes was associated with MRSA colonization in the oropharynx
      (OR=3.3, P=.02). CONCLUSION: Use of indwelling devices is associated with greater
      colonization with antimicrobial-resistant pathogens. This study serves as an
      initial step in defining a high-risk group that merits intensive infection
      control efforts.

PMID- 18081671
TI  - The effect of age on outcomes of sling surgery for urinary incontinence.
AB  - OBJECTIVES: To measure the effect of patient age on outcomes of sling surgery for
      stress urinary incontinence. DESIGN: Analysis of Medicare claims data. SETTING:
      Analysis of the 1999 to 2001 Medicare Public Use Files provided by the Centers
      for Medicare and Medicaid Services on a 5% national random sample of
      beneficiaries. PARTICIPANTS: Women who underwent sling procedures between July 1,
      1999, and December 31, 2000, were identified according to Common Procedural
      Terminology, Fourth Edition, code 57288 (sling operation for stress
      incontinence). Subjects were tracked for 6 months before surgery to identify
      preoperative comorbidities and for 12 months after surgery to assess short-term
      complications. Subjects were stratified for analysis at age 75. MEASUREMENTS:
      Bivariate analyses were conducted with patients stratified at age 75, and
      multivariate analyses were also conducted to identify the independent effects of
      patient age and comorbidities on outcomes. RESULTS: A total of 1,356 procedures
      were performed during the 18-month index period. This extrapolates to 27,120
      procedures in all Medicare beneficiaries. At 1 year after surgery, overall
      outcomes in younger women (aged 65-74) were significantly better than in older
      women with respect to postoperative urge incontinence (20.0% vs 12.6%), treatment
      failure (10.5% vs 7.2%), and outlet obstruction (10.5% vs 6.6%). Older age and
      greater comorbidity were associated with greater risk of nonurological events
      (e.g., pulmonary embolism and cardiac events). CONCLUSION: Women aged 75 and
      older are more likely to experience postoperative urge incontinence, treatment
      failure, and outlet obstruction after sling surgery. Older age and comorbidities
      were associated with higher rates of nonurological complications.

PMID- 18081672
TI  - Effects of change in physical activity on physical function limitations in older
      women: mediating roles of physical function performance and self-efficacy.
AB  - OBJECTIVES: To examine the hypothesis that changes in self-efficacy and
      functional performance mediate, in part, the beneficial effect of physical
      activity on functional limitations over time. DESIGN: Prospective, observational
      study. SETTING: Community-based. PARTICIPANTS: Two hundred forty-nine community
      dwelling older women. MEASUREMENTS: Participants completed measures of self
      reported physical activity, functional limitations, and self-efficacy. Four
      measures of physical function performance were also assessed. Measures were
      completed at baseline and 24 months. Data were analyzed using a panel model
      within a covariance modeling framework. RESULTS: Results indicated that increases
      in physical activity over time were associated with greater improvements in self
      efficacy, which was associated in turn with improved physical function
      performance, both of which mediated the association between physical activity and
      functional limitations. Fewer functional limitations at baseline were also
      associated with higher levels of self-efficacy at 24 months. Age, race, and
      health status covariates did not significantly change these relationships.
      CONCLUSION: The findings support the mediating roles of self-efficacy and
      physical function performance in the relationship between longitudinal changes in
      physical activity and functional limitations in older women.

PMID- 18081674
TI  - The development of academic geriatric medicine: progress toward preparing the
      nation's physicians to care for an aging population.
AB  - Academic geriatric medicine programs are critical for training the physician
      workforce to care effectively for aging Americans. This article describes the
      progress made by medical schools in developing these programs. Academic leaders
      in geriatrics at all 145 accredited allopathic and osteopathic medical schools in
      the United States were surveyed in the winter of 2005 (68% response rate) and
      results compared with findings from a similar 2001 survey. Physician faculty in
      geriatrics at U.S. medical schools increased from 7.5 (mean) full-time
      equivalents (FTEs) in 2001 to 9.6 FTEs in 2005. Faculty and staff effort is
      mostly devoted to clinical practice (mean 36.9%) and education (mean 34.6%). A
      small number of programs focus on research; only six responding schools devote
      more than 40% of faculty effort to research. Seventy-one percent reported that
      their medical school required a geriatrics medical student clerkship or that
      their geriatric training was integrated into a required clinical rotation. In
      summary, from 2001 to 2005, more fellows and faculty have been recruited and
      trained, and some academic programs have emerged with strong education, research,
      and clinical initiatives. Medical student exposure to geriatrics curriculum has
      increased, although few academic geriatricians are pursuing research careers, and
      the number of practicing geriatricians is declining. An expanded investment in
      training the physician workforce to care for older adults will be required to
      ensure adequate care for aging Americans.

PMID- 18081673
TI  - After-hours calls from long-term care facilities in a geriatric medicine training
      program.
AB  - OBJECTIVES: To describe after-hours telephone calls from nurses in long-term care
      (LTC) facilities to doctors in a geriatric medicine training program. DESIGN:
      Evaluation of 1,928 after-hours calls from LTC facilities over a 10-month period
      in 2005/06. SETTING: Geriatrics fellowship program and three affiliated LTC
      facilities. PARTICIPANTS: Eight geriatrics fellows and 40 medicine interns.
      MEASUREMENTS: Data were collected on call characteristics (such as reason for
      call and call outcome) and physician attitudes about the call, scored using a 5
      point Likert scale. RESULTS: Clinical problems were the focus of 70.4% of the
      calls. The range of clinical problems was broad; most common reasons for calls
      were falls (n=377), pain (n=138), and agitation (n=100). The majority of calls
      resulted in medical intervention, including new medications or treatments
      (43.4%), diagnostic tests (10.2%), or more-extensive medical evaluation in the
      emergency department (9.1%) or by an on-site physician (2.4%). Overall, physician
      trainees had favorable attitudes about most after-hours calls, although medicine
      interns taking calls had a less-favorable impression and felt less prepared to
      manage them. CONCLUSION: After-hours telephone calls from LTC facilities are
      common, reflect the heterogeneity of geriatric health concerns, and typically
      result in intervention. As the LTC population grows, more study is needed on
      telephone care and optimal strategies for training physicians in this important
      aspect of LTC.

PMID- 18081675
TI  - Improving evidence-based management of depression for older Americans in primary
      care: if not now, when?

PMID- 18081676
TI  - Thoughts on the development of geriatrics.

PMID- 18081677
TI  - The circle.

PMID- 18081678
TI  - Smoking and mortality in the oldest-old, evidence from a prospective cohort of
      56,000 Hong Kong Chinese.

PMID- 18081680
TI  - Geriatric syndromes.

PMID- 18081681
TI  - Small intestinal intussusceptions caused by percutaneous endoscopic jejunostomy
      tube placement.

PMID- 18081682
TI  - Subungual melanoma: a particularly invasive "onychomycosis".

PMID- 18081683
TI  - A transient increase in cerebrospinal fluid tau level after epileptic seizure in
      an elderly patient.

PMID- 18081684
TI  - Are recurrent fallers depressed?

PMID- 18081685
TI  - Cholinesterase inhibitors and use of psychotropic medications in a sample of
      patients with dementia.

PMID- 18081686
TI  - Erythrocyte volume is a poor predictor of cobalamin and folate deficiency in
      geriatric patients.

PMID- 18081687
TI  - The close association between low economic status and glucose intolerance in
      elderly subjects in a rural area in Laos.

PMID- 18081688
TI  - Altered blood pressure homeostasis in the oldest old and survival.

PMID- 18081689
TI  - Curriculum development in geriatric medicine for obstetrics and gynecology
      residents.

PMID- 18081690
TI  - Translational mini-review series on complement factor H: genetics and disease
      associations of human complement factor H.
AB  - Factor H is an abundant plasma glycoprotein that plays a critical role in the
      regulation of the complement system in plasma and in the protection of host cells
      and tissues from damage by complement activation. Several recent studies have
      described the association of genetic variations of the complement factor H gene
      (CFH) with atypical haemolytic uraemic syndrome (aHUS), age-related macular
      degeneration (AMD) and membranoproliferative glomerulonephritis (MPGN). This
      review summarizes our current knowledge of CFH genetics and examines the CFH
      genotype-phenotype correlations that are helping to understand the molecular
      basis underlying these renal and ocular pathologies.

PMID- 18081693
TI  - Intravital multi-photon microscopy reveals several levels of heterogeneity in
      endocytic uptake by mouse renal proximal tubules.
AB  - Understanding renal function requires one to integrate the structural complexity
      of kidney nephrons and the dynamic nature of their cellular processes. Multi
      photon fluorescence microscopy is a state-of-the-art imaging technique for in
      vivo analysis of kidney tubules structure and function in real time. This study
      presents visual evidence for several levels of heterogeneity of proximal tubular
      endocytic uptake in the superficial renal mouse cortex and illustrates the
      potential of multi-photon microscopy for providing a comprehensive and dynamic
      portrayal of renal function.

PMID- 18081691
TI  - Translational mini-review series on complement factor H: structural and
      functional correlations for factor H.
AB  - The 155-kDa glycoprotein, complement factor H (CFH), is a regulator of complement
      activation that is abundant in human plasma. Three-dimensional structures of over
      half the 20 complement control protein (CCP) modules in CFH have been solved in
      the context of single-, double- and triple-module segments. Proven binding sites
      for C3b occupy the N and C termini of this elongated molecule and may be brought
      together by a bend in CFH mediated by its central CCP modules. The C-terminal CCP
      20 is key to the ability of the molecule to adhere to polyanionic markers on self
      surfaces where CFH acts to regulate amplification of the alternative pathway of
      complement. The surface patch on CCP 20 that binds to model glycosaminoglycans
      has been mapped using nuclear magnetic resonance (NMR), as has a second
      glycosaminoglycan-binding patch on CCP 7. These patches include many of the
      residue positions at which sequence variations have been linked to three
      complement-mediated disorders: dense deposit disease, age-related macular
      degeneration and atypical haemolytic uraemic syndrome. In one plausible model,
      CCP 20 anchors CFH to self-surfaces via a C3b/polyanion composite binding site,
      CCP 7 acts as a 'proof-reader' to help discriminate self- from non-self patterns
      of sulphation, and CCPs 1-4 disrupt C3/C5 convertase formation and stability.

PMID- 18081694
TI  - Cytokine-induced beta-cell apoptosis is NO-dependent, mitochondria-mediated and
      inhibited by BCL-XL.
AB  - Pro-inflammatory cytokines are implicated as the main mediators of beta-cell
      death during type 1 diabetes but the exact mechanisms remain unknown. This study
      examined the effects of interleukin-1beta (IL-1beta), interferon-gamma (IFNgamma)
      and tumour necrosis factor alpha (TNFalpha) on a rat insulinoma cell line (RIN-r)
      in order to identify the core mechanism of cytokine-induced beta-cell death.
      Treatment of cells with a combination of IL-1beta and IFNgamma (IL
      1beta/IFNgamma)induced apoptotic cell death. TNFalpha neither induced beta-cell
      death nor did it potentiate the effects of IL-1beta, IFNgamma or IL
      1beta/IFNgamma . The cytotoxic effect of IL-1beta/IFNgamma was associated with
      the expression of inducible nitric oxide synthase (iNOS) and production of nitric
      oxide. Adenoviral-mediated expression of iNOS (AdiNOS) alone was sufficient to
      induce caspase activity and apoptosis. The broad range caspase inhibitor, Boc-D
      fmk, blocked IL-1beta/IFNgamma -induced caspase activity, but not nitric oxide
      production nor cell death. However, pre-treatment with L-NIO, a NOS inhibitor,
      prevented nitric oxide production, caspase activity and reduced apoptosis. IL
      1beta/IFNgamma -induced apoptosis was accompanied by loss of mitochondrial
      membrane potential, release of cytochrome c and cleavage of pro-caspase-9, -7 and
      -3. Transduction of cells with Ad-Bcl-X(L) blocked both iNOS and cytokine
      mediated mitochondrial changes and subsequent apoptosis, downstream of nitric
      oxide. We conclude that cytokine-induced nitric oxide production is both
      essential and sufficient for caspase activation and beta-cell death, and have
      identified Bcl-X(L) as a potential target to combat beta-cell apoptosis.

PMID- 18081695
TI  - The Pseudomonas aeruginosa Type III secretion system plays a dual role in the
      regulation of caspase-1 mediated IL-1beta maturation.
AB  - Pseudomonas aeruginosa is an opportunistic bacterial pathogen that forms a
      serious problem for immunocompromised patients and also the leading cause of
      mortality in cystic fibrosis. The overall importance of a functional Type III
      secretion system (T3SS) in P. aeruginosa virulence has been well established, but
      the underlying mechanisms are still unclear. Using in vitro infected macrophages
      as w as a murine model of acute lung infection, we show that the Caspase-1
      mediated maturation and secretion of IL-1beta needs a translocation competent
      T3SS and Flagellin, but not the Type III effector proteins ExoS, ExoT and ExoY.
      However, ExoS was found to negative regulate the P. aeruginosa induced IL-1beta
      maturation by a mechanism that is dependent on its ADP ribosyltransferase
      activity. Moreov ExoS deficiency also switched the mode of macrophage death from
      apoptosis to pro-inflammatory pyroptosis. Altogether, these data demonstrate a
      dual role for the P. aeruginosa T3SS in the regulation of Caspase-1 mediated IL
      1beta production and provide new insights into the mechanisms of immune evasion
      by this pathogen.

PMID- 18081697
TI  - Mucin immunohistochemistry in the diagnosis and mapping of extramammary Paget's
      disease.
AB  - Extramammary Paget's disease (EMPD) is a rare skin cancer of the genital region
      in which cancer cells with enlarged nuclei and pale cytoplasm are scattered
      singly in the affected epidermis. These cancer cells, called Paget cells, contain
      mucin, which is never found in normal epidermis. The oligosaccharide side chains
      of Paget cell mucin end with sialic acid. Sialic acid is easily detected by
      zirconyl haematoxylin or alcian blue. The other sugars in the oligosaccharide
      chains can be detected by the periodic acid-Shiff reaction. Rarely, the diagnosis
      of EMPD is complicated by the absence of mucin from the Paget cells. We have
      examined such an atypical case. The oligosaccharide side chains, including the
      sialic acids, are absent. In both this case and a typical case, the Paget cells
      contain epithelial membrane antigen mucin (MUC1) core protein and usually contain
      gastric surface-type mucin (MUC5AC) core protein, which can be stained by
      antibodies. Since neither core protein is found in normal epidermis, epithelial
      membrane antigen core protein may be the most reliable diagnostic marker for
      extramammary Paget's disease. In both the atypical case and the typical case of
      Paget's disease, some cells that look like keratinocytes contain mucin core
      proteins. These may be incipient Paget cells. We suggest that using th epithelial
      membrane antigen core protein as a marker for the true extent of extramammary
      Paget's disease could facilitate complete excision and reduce the rate of
      recurrence.

PMID- 18081700
TI  - A clinicopathological study of 13 cases of intravascular lymphoma: experience in
      a single institution over a 9-yr period.
AB  - Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma in which the
      lymphoma cells proliferate exclusively in lumina of small vessels. Here, we
      report a clinicopathological study of 13 cases IVL diagnosed at our institution
      between March 1999 and July 2007, and evaluated the clinical characteristics,
      usefulness of random skin biopsy and response to chemotherapy containing
      rituximab. Three of 13 patients were diagnosed at autopsy. The most common
      clinical features were unexplained fever, neurological deterioration, respiratory
      failure, and poor performance status. Thrombocytopenia, high serum lactate
      dehydrogenase and soluble interleukin2 receptor levels were the most common
      laboratory abnormalities. Adrenal tumor was detected in four cases and pituitary
      involvement was seen in all three autopsied cases and in two surviving patient by
      brain magnetic resonance imaging. Bone marrow invasion was seen in all 13 cases
      by bone marrow smear, and it was subtle in trephine biopsy. Immunohistochemical
      analyses revealed that CD5 was positive in one-third of the cases. Most of the
      cases were positive for MUM1/IRF, Bcl-2 and negative for CD10 and BCL-6
      indicating the postgerminal center cell origin of this peculiar type of lymphoma.
      On random skin biopsy, the most recent seven patients were diagnosed promptly and
      chemotherapy containing rituximab was successfully administered. Patients with
      IVL exhibit the characteristic clinical and immunophenotypic features cited above
      and the use of random skin biopsy facilitates prompt diagnosis. Early
      commencement of chemotherapy containing rituximab appears promising for this
      peculiar lymphoma. As the recent seven patients were diagnosed by random skin
      biopsy over the past 13 months, the incidence of IVL is thought to be much higher
      than generally accepted.

PMID- 18081698
TI  - Expression of the NF-kappaB inhibitor ABIN-3 in response to TNF and toll-like
      receptor 4 stimulation is itself regulated by NF-kappaB.
AB  - Although the nuclear factor-kappaB (NF-kappaB)-dependent gene expression is
      critical to the induction of an efficient immune response to infection or tissue
      injury, excessive or prolonged NF-kappaB signalling can contribute to the
      development of several inflammatory diseases. Therefore, the NF-kappaB signal
      transduction pathway is tightly regulated by several intracellular proteins. We
      have previously identified A20-binding inhibitor of NF-kappaB activation (ABIN)-3
      as an lipopolysaccharide (LPS)-inducible protein in monocytes that negatively
      regulates NF-B activation in response to tumour necrosis factor (TNF) and LPS.
      Here we report that ABIN-3 expression is also up-regulated upon TNF treatment of
      monocytes and other non-myeloid cell types. We also found a significantly
      enhanced expression of ABIN-3 in monocytes of sepsis patients, which is restored
      to control levels by corticotherapy. To further understand the transcriptional
      regulation of ABIN-3 expression, we isolated the human ABIN-3 promoter and
      investigated its activation in response to TNF and LPS. This revealed that the
      LPS- and TNF-inducible expression of ABIN-3 is dependent on the binding of NF
      kappaB to a specific B site in the ABIN-3 promoter. Altogether, these data
      indicate an important role for NF-kappaB-dependent gene expression of ABIN-3 in
      the negative feedback regulation of TNF receptor and toll-like receptor 4 induced
      NF-kappaB activation.

PMID- 18081701
TI  - Functional impairment of hematopoietic progenitor cells in patients with coronary
      heart disease.
AB  - The circulating form of endothelial progenitors cells (EPCs) are derived from
      bone marrow (BM)-derived hematopoietic stem cells (HSCs). Enhanced mobilization
      of EPCs was shown to be linked to cardiac diseases. This study investigated
      whether reduced EPC levels in advanced coronary heart disease (CHD) are secondary
      to a functional exhaustion of HSCs in the BM or to reduced mobilization. Number
      and functional properties of EPCs were assessed in 15 healthy controls, and 40
      patients with CHD. The colony-forming unit (CFU) capacity of BM-derived
      mononuclear cells and the CD34+ HSC number were examined in four healthy
      volunteers, and 15 CHD patients. EPC number was reduced in CHD patients (P < 0.01
      vs. controls). Moreover, the migratory capacity was significantly impaired in
      EPCs of CHD patients (P < 0.05 vs. controls). On multivariate analysis, CHD was
      an independent predictor of functional EPC impairment. CFUs were reduced in CHD
      patients (59.6 +/- 21.2 vs. 75.4 +/- 25.8 in controls, P < 0.05). CHD was also
      predictor of impaired CFU capacity. In this small clinical study, CHD is
      associated with selective impairment of HSC function in the BM and in the
      peripheral blood, which may contribute to impairment of cardiac function.

PMID- 18081702
TI  - Impact of cytomegalovirus serostatus on outcome of unrelated cord blood
      transplantation for adults: a single-institute experience in Japan.
AB  - Cytomegalovirus (CMV) disease is one of the major infectious complications after
      allogeneic hematopoietic stem cell transplantation (SCT). Several studies have
      shown that CMV-seropositive patients have a substantial survival disadvantage
      after bone marrow transplantation (BMT) or peripheral blood SCT (PBSCT). Between
      August 1998 and February 2006, 101 adult patients underwent myeloablative cord
      blood transplantation (CBT) from unrelated donors at our institution. Sixteen and
      85 patients were CMV-seronegative and CMV-seropositive, respectively, prior to
      CBT. Outcomes of CBT were compared between CMV-seronegative and CMV-seropositive
      patients. The cumulative incidences of neutrophil engraftment at 60 d after CBT
      did not differ between CMV-seronegative and CMV-seropositive patients (100% and
      94%, P = 0.09); however, the cumulative incidence of platelet engraftment at 100
      d was higher in CMV-seronegative patients than CMV-seropositive patients (100%
      vs. 86%, P < 0.005). The cumulative incidence of CMV antigenemia at 100 d was
      lower in CMV-seronegative patients than CMV-seropositive patients (0% vs. 77%, P
      < 0.001); however, the cumulative incidences of CMV disease did not differ
      between CMV-seronegative and CMV-seropositive patients (0% vs. 1%, P = 0.84). The
      probabilities of disease-free survival at 2 yr also did not differ between CMV
      seronegative and CMV-seropositive patients (92% vs. 72%, P = 0.16). The outcomes
      of CBT for CMV-seropositive patients as well as CMV-seronegative patients in our
      series were favorable. This might be due to effective antiviral therapy for CMV
      infection. Large-scale studies are needed to determine the impact of recipient
      CMV serostatus on the outcome of CBT for adults.

PMID- 18081703
TI  - Spontaneous rupture of the spleen as immediate complication in autologous
      transplantation for primary systemic amyloidosis.
AB  - Although splenic rupture is a recognized complication of primary amyloidosis,
      very few cases have been reported in the context of stem cell transplantation. A
      patient with systemic primary amyloidosis with renal and cardiac involvement and
      factor X deficiency, who developed a splenic rupture 24 h after the peripheral
      blood stem cells infusion during autologous transplantation, is described. This
      complication has been reported during stem cell mobilization and after post
      transplant hematopoietic recovery, but we have not found a previous report of
      splenic rupture in the immediate postinfusion period. This case illustrates that
      splenic rupture can occur at any time during the transplant procedure. Need for
      close monitoring, particularly in patients with factor X deficiency after
      receiving granulocyte colony stimulating factor, two recently recognized risk
      factors for splenic hemorrhage, is highlighted.

PMID- 18081704
TI  - Congenital dyserythropoietic anaemia, type I, in a Caucasian patient with retinal
      angioid streaks (homozygous Arg1042Trp mutation in codanin-1).
AB  - A congenital dyserythropoietic anaemia (CDA) was recognised in a French Caucasian
      male patient. Blood smears showed a pronounced aniso-poikilocytosis. Bone marrow
      light microscopy showed signs of dyserythropoesis, but no internuclear chromatin
      bridges. Electron microscopy disclosed erythroblast nuclei with the Swiss cheese
      aspect and the presence of cytoplasmic organelles, assessing the diagnosis of CDA
      I. The presence of internuclear chromatin bridges may thus be missing in CDA I.
      The patient proved to be homozygous for the Arg1042Trp mutation in codanin-1 (the
      'Bedouin mutation'). By the age of 25, the patient's vision started to
      deteriorate as a result of retinal angioid streaks and macular abnormalities.
      Evolution was controlled and the patient, being nearly 50 yr old now, still has a
      partial use of his eyes. This second case of retinal angioid streaks reported in
      CDA I adds to the non-haematological features likely to be associated with this
      condition.

PMID- 18081705
TI  - Cytogenetic studies at diagnosis in polycythemia vera: clinical and JAK2V617F
      allele burden correlates.
AB  - The prognostic significance of cytogenetic findings at diagnosis in polycythemia
      vera (PV) was investigated in a retrospective series of 137 patients.
      Cytogenetics were normal in 117 patients (85%) and displayed a -Y abnormality in
      five patients (7% of male patients), and other chromosomal abnormalities in 15
      patients (11%). The most frequent cytogenetic anomalies were trisomy 8 (n = 4),
      trisomy 9 (n = 2), deletion 20q (n = 2) and chromosomal 1 abnormalities (n = 2).
      Parameters that were significantly associated with abnormal cytogenetics included
      age > or = 60 yr (P = 0.02), but not JAK2V617F allele burden, thrombosis,
      hemorrhage, leukemic/fibrotic transformation, or survival. We conclude that
      cytogenetic anomalies occur infrequently at PV diagnosis and do not confer an
      adverse outcome.

PMID- 18081706
TI  - Beta-thalassemia intermedia due to two novel mutations in the promoter region of
      the beta-globin gene.
AB  - Two novel beta-thalassemia mutations affecting the promoter region of the beta
      globin gene are described. The first mutation, found in a Moroccan family, is a G
      ->A substitution at position -190 relative to the beta-globin gene Cap site. The
      second, found in an Algerian patient, is a G-->C substitution at position -56
      relative to the beta-globin Cap site. These two mutations occur in a region (-50
      to -300) where promoter elements important for differential control of gene
      expression have been described and lead to beta-thalassemia intermedia in
      association with a beta(0)-thalassemia mutations.

PMID- 18081707
TI  - Treatment of adult T-cell leukemia/lymphoma: past, present, and future.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy caused by
      human T-cell lymphotrophic virus type I. Clinical manifestations of ATLL range
      from smoldering to chronic, lymphoma and acute. Patients with acute and lymphoma
      type ATLL require therapeutic intervention. Conventional chemotherapeutic
      regimens used against other malignant lymphoma have been administered to ATLL
      patients, but the therapeutic outcomes of acute and lymphoma type ATLL remain
      very poor. Promising results of allogeneic stem cell transplantation (SCT) for
      ATLL patients have recently been reported and the treatment outcome might be
      improved for some ATLL patients. Besides conventional chemotherapy and SCT,
      interferon, zidovudine, arsenic trioxide, targeted therapy against surface
      molecule on ATLL cells, retinoid derivatives, and bortezomib have been
      administered to ATLL patients in pilot or phase I/II studies. Further studies are
      required to confirm the clinical benefits of these novel therapeutics. This
      article reviews the current status and future directions of ATLL treatment.

PMID- 18081708
TI  - Enhancement of T cell activation by immobilized hu5C8 (anti-CD40L) monoclonal
      antibody.
AB  - BACKGROUND: Soluble monoclonal antibodies (MoAb) targeting CD40L on T cells can
      partially block T cell alloreactivity by preventing the costimulatory signal of
      antigen presenting cells through CD40. However, it is not known if these MoAbs
      can also deliver inhibiting or stimulating signals through the CD40L receptor.
      MATERIALS AND METHODS: Blood mononuclear cells were stimulated by mitogens or
      allogeneic stimulator cells in the presence of hu5C8 MoAb, either in soluble
      form, or immobilized to the culture wells. T cell responses were evaluated by
      means of primary and secondary mixed lymphocyte culture (MLC), cytotoxic T
      lymphocyte (CTL) generation, immunophenotype, apoptosis assay and cytokine
      release. Also, the effect of hu5C8 on cells inhibited by CTLA4-Ig was tested.
      RESULTS: While the soluble hu5C8 inhibited T cell proliferation, the immobilized
      hu5C8 enhanced both mitogen and alloantigen-induced proliferative and cytotoxic T
      cell responses, without inducing further apoptotic T cell death. In the presence
      of CTLA4-Ig, immobilized hu5C8 increased the residual CD28-independent
      proliferation of alloantigen-specific T cells both in primary and secondary MLC,
      and prevented the inhibiting effect of CTLA4-Ig on the generation of CTL.
      Immobilized hu5C8 MoAb-stimulated T cells also showed a limited capacity of
      producing interleukin (IL)-10, even in the presence of CTLA4-Ig. CONCLUSIONS: We
      show that the hu5C8 MoAb has a strong mitogenic activity when immobilized, likely
      due to higher crosslinking capacity as compared to the soluble antibody.
      Strategies to induce ex-vivo T cell responses against tumor or viral antigens by
      means of hu5C8 MoAb antibody will be exploited based on these findings.

PMID- 18081709
TI  - CD44 and hyaluronan engagement promotes dexamethasone resistance in human myeloma
      cells.
AB  - Dexamethasone (Dex) is an effective therapeutic agent against multiple myeloma
      (MM); however, resistance to it often becomes a clinical issue. CD44 is an
      adhesion molecule that serves as a cell surface receptor for extracellular matrix
      components, including hyaluronan (HA). HA is an extracellular matrix component
      that is involved in survival and progression in MM. In the present report, we
      describe isolation of a CD44-expressing population from a Dex-sensitive MM cell
      line, RPMI8226, in which the CD44-high population had a significantly higher
      potential to resist Dex than did the CD44-low population. Furthermore, we
      demonstrate that CD44 engagement by an anti-CD44 monoclonal antibody (mAb) or HA
      protects MM cells from Dex-induced growth inhibition. The activity of HA was
      partially inhibited by blocking its binding to CD44, indicating that CD44
      mediates HA activity promoting MM cell survival. CD44 engagement by an anti-CD44
      mAb led to phosphorylation and degradation of IkappaB-alpha, thus preventing its
      Dex-induced up-regulation. Our data suggest that CD44 is not only an important
      mediator for the survival activity of HA, but it may also contribute to MM cell
      resistance to Dex.

PMID- 18081711
TI  - Effects of early experience and genotype on serotonin transporter regulation in
      infant rhesus macaques.
AB  - The moderating effect of early experience on gene-behavior associations has been
      well characterized. The molecular events that allow for such moderation are not
      well understood, however. We assessed the impact of early experience and
      serotonin transporter linked promoter polymorphism (rh5-HTTLPR) genotype on
      peripheral serotonin transporter (5-HTT) regulation in response to a
      maternal/social separation and relocation stressor in infant rhesus macaques. We
      further tested the hypothesis that modulation of 5-HTT regulation by rearing
      and/or genotype is mediated by glucocorticoid (GC) availability. Fifty-three
      infant (3-4 months of age) rhesus macaques that were either nursery reared (NR)
      or mother reared (MR) were genotyped for rh5-HTTLPR. Infants were blood sampled
      within 2.5 h of maternal or social separation/relocation and again 5 h later.
      Infants were then administered dexamethasone, a synthetic GC and blood sampled
      16.5 h later. 5-HTT RNA was quantified from peripheral blood mononuclear cells.
      Plasma cortisol was measured at all time points. The MR individuals upregulated 5
      HTT significantly during maternal/social separation, while NR individuals did
      not. Concomitant increases in cortisol were not observed, but dexamethasone
      treatment stimulated 5-HTT expression regardless of genotype/rearing group, and 5
      HTT expression in the post-stressor sample was correlated with plasma cortisol
      levels at all time points. Our data indicate that early experience exerted a
      strong influence on 5-HTT regulation during a stressor in infant rhesus macaques
      independent of rh5-HTTLPR genotype. We also showed that GCs may stimulate 5-HTT
      expression but that there likely exist faster-acting transcriptional regulators
      of 5-HTT that are in place as a function of experience.

PMID- 18081710
TI  - Multivariate permutation analysis associates multiple polymorphisms with
      subphenotypes of major depression.
AB  - Unipolar major depressive disorder (MDD) is a prevalent, disabling condition with
      multiple genetic and environmental factors impacting disease risk. The diagnosis
      of MDD relies on a cumulative measure derived from multiple trait dimensions and
      alone is limited in elucidating MDD genetic determinants. We and others have
      proposed that MDD may be better dissected using paradigms that assess how
      specific genes associate with component features of MDD. This within-disease
      design requires both a well-phenotyped cohort and a robust statistical approach
      that retains power with multiple tests of genetic association. In the present
      study, common polymorphic variants of genes related to central monoaminergic and
      cholinergic pathways that previous studies align with functional change in vitro
      or depression associations in vivo were genotyped in 110 individuals with
      unipolar MDD. Subphenotypic characteristics were examined using responses to
      individual items assessed with the Structured Clinical Interview for Diagnostic
      and Statistical Manual of Mental Disorders (DSM IV), the 17-item Hamilton Rating
      Scale for Depression (HAM-D) and the NEO Five Factor Inventory. Multivariate
      Permutation Testing (MPT) was used to infer genotype-phenotype relationships
      underlying dimensional findings within clinical categories. MPT analyses show
      significant associations of the norepinephrine transporter (NET, SLC6A2) -182 T/C
      (rs2242446) with recurrent depression [odds ratio, OR = 4.15 (1.91-9.02)], NET 
      3081 A/T (rs28386840) with increase in appetite [OR = 3.58 (1.53-8.39)] and the
      presynaptic choline transporter (CHT, SLC5A7) Ile89Val (rs1013940) with HAM-D-17
      total score {i.e. overall depression severity [OR = 2.74 (1.05-7.18)]}. These
      relationships illustrate an approach to the elucidation of gene influences on
      trait components of MDD and with replication, may help identify MDD
      subpopulations that can benefit from more targeted pharmacotherapy.

PMID- 18081712
TI  - Neuronal cell adhesion molecule deletion induces a cognitive and behavioral
      phenotype reflective of impulsivity.
AB  - Cell adhesion molecules, such as neuronal cell adhesion molecule (Nr-CAM),
      mediate cell-cell interactions in both the developing and mature nervous system.
      Neuronal cell adhesion molecule is believed to play a critical role in cell
      adhesion and migration, axonal growth, guidance, target recognition and synapse
      formation. Here, wild-type, heterozygous and Nr-CAM null mice were assessed on a
      battery of five learning tasks (Lashley maze, odor discrimination, passive
      avoidance, spatial water maze and fear conditioning) previously developed to
      characterize the general learning abilities of laboratory mice. Additionally, all
      animals were tested on 10 measures of sensory/motor function, emotionality and
      stress reactivity. We report that the Nr-CAM deletion had no impact on four of
      the learning tasks (fear conditioning, spatial water maze, Lashley maze and odor
      discrimination). However, Nr-CAM null mice exhibited impaired performance on a
      task that required animals to suppress movement (passive avoidance). Although Nr
      CAM mutants expressed normal levels of general activity and body weights, they
      did exhibit an increased propensity to enter stressful areas of novel
      environments (the center of an open field and the lighted side of a dark/light
      box), exhibited higher sensitivity to pain (hot plate) and were more sensitive to
      the aversive effects of foot shock (shock-induced freezing). This behavioral
      phenotype suggests that Nr-CAM does not play a central role in the regulation of
      general cognitive abilities but may have a critical function in regulating
      impulsivity and possibly an animal's susceptibility to drug abuse and addiction.

PMID- 18081713
TI  - Evolution toward a new adaptive optimum: phenotypic evolution in a fossil
      stickleback lineage.
AB  - Natural selection has almost certainly shaped many evolutionary trajectories
      documented in fossil lineages, but it has proven difficult to demonstrate this
      claim by analyzing sequences of evolutionary changes. In a recently published and
      particularly promising test case, an evolutionary time series of populations
      displaying armor reduction in a fossil stickleback lineage could not be
      consistently distinguished from a null model of neutral drift, despite excellent
      temporal resolution and an abundance of indirect evidence implicating natural
      selection. Here, we revisit this case study, applying analyses that differ from
      standard approaches in that: (1) we do not treat genetic drift as a null model,
      and instead assess neutral and adaptive explanations on equal footing using the
      Akaike Information Criterion; and (2) rather than constant directional selection,
      the adaptive scenario we consider is that of a population ascending a peak on the
      adaptive landscape, modeled as an Orstein-Uhlenbeck process. For all three
      skeletal features measured in the stickleback lineage, the adaptive model
      decisively outperforms neutral evolution, supporting a role for natural selection
      in the evolution of these traits. These results demonstrate that, at least under
      favorable circumstances, it is possible to infer in fossil lineages the
      relationship between evolutionary change and features of the adaptive landscape.

PMID- 18081714
TI  - Partitioning adaptive differentiation across a patchy landscape: shade avoidance
      traits in impatiens capensis.
AB  - Adaptation to different habitat types across a patchy landscape may either arise
      independently in each patch or occur due to repeated colonization of each patch
      by the same specialized genotype. We tested whether open- and closed-canopy forms
      of Impatiens capensis, an herbaceous annual plant of eastern North America, have
      evolved repeatedly by comparing hierarchical measures of F(ST) estimated from
      AFLPs to morphological differentiation measured by Q(ST) for five pairs of
      populations found in open and closed habitats in five New England regions.
      Morphological differentiation between habitats (Q(HT)) in elongation traits was
      greater than marker divergence (F(HT)), suggesting adaptive differentiation.
      Genotypes from open- and closed-canopy habitats differed in shade avoidance
      traits in several population pairs, whereas patterns of AFLP differentiation
      suggest this differentiation does not have a single origin. These results suggest
      that open- and closed-canopy habitats present different selective pressures, but
      that the outcome of diversifying selection may differ depending on specific
      closed- and open-canopy habitats and on starting genetic variation. Hierarchical
      partitioning of F(ST) and Q(ST) makes it possible to distinguish global
      stabilizing selection on traits across a landscape from diversifying selection
      between habitat types within regions.

PMID- 18081715
TI  - Polyandry facilitates postcopulatory inbreeding avoidance in house mice.
AB  - The avoidance of genetic incompatibilities between parental genotypes has been
      proposed to account for the evolution of polyandry. An extension of this
      hypothesis suggests polyandry may provide an opportunity for females to avoid the
      cost of inbreeding by exploiting postcopulatory mechanisms that bias paternity
      toward unrelated male genotypes. Here we test the inbreeding avoidance hypothesis
      in house mice by experimentally manipulating genetic compatibility via matings
      between siblings and nonsiblings. We observed little difference in reproductive
      success between females mated to two siblings or females mated to two
      nonsiblings. Females mated to both a sibling and a nonsibling tended to have a
      lower litter survival, but only when the first male to mate was a sibling.
      Microsatellite data revealed that paternity was biased toward nonsiblings when a
      female mated with both a sibling and a nonsibling. Unlike previous studies of
      invertebrates, paternity bias toward the sibling male was independent of mating
      sequence. We provide one of the first empirical demonstrations that polyandry
      facilitates postcopulatory sexual selection in a vertebrate. We discuss this
      result in relation to the possibility of selective fertilization of ova based on
      major histocompatibility complex (MHC) haploid expression of sperm.

PMID- 18081717
TI  - Interpopulation hybrid breakdown maps to the mitochondrial genome.
AB  - Hybrid breakdown, or outbreeding depression, is the loss of fitness observed in
      crosses between genetically divergent populations. The role of maternally
      inherited mitochondrial genomes in hybrid breakdown has not been widely examined.
      Using laboratory crosses of the marine copepod Tigriopus californicus, we report
      that the low fitness of F(3) hybrids is completely restored in the offspring of
      maternal backcrosses, where parental mitochondrial and nuclear genomic
      combinations are reassembled. Paternal backcrosses, which result in mismatched
      mitochondrial and nuclear genomes, fail to restore hybrid fitness. These results
      suggest that fitness loss in T. californicus hybrids is completely attributable
      to nuclear-mitochondrial genomic interactions. Analyses of ATP synthetic capacity
      in isolated mitochondria from hybrid and backcross animals found that reduced ATP
      synthesis in hybrids was also largely restored in backcrosses, again with
      maternal backcrosses outperforming paternal backcrosses. The strong fitness
      consequences of nuclear-mitochondrial interactions have important, and often
      overlooked, implications for evolutionary and conservation biology.

PMID- 18081718
TI  - Clinical impact of nucleophosmin mutations and Flt3 internal tandem duplications
      in patients older than 60 yr with acute myeloid leukaemia.
AB  - BACKGROUND: Nucleophosmin (NPM1) and Flt3 internal tandem duplications (Flt3-ITD
      mutations) represent the most frequent molecular aberrations in patients with
      acute myeloid leukemia (AML). While NPM1 mutations are associated with favourable
      prognosis in younger AML patients, Flt3-ITD mutations reflect an unfavourable
      prognostic factor in these patients. So far, especially NPM1 mutations have not
      yet been evaluated exclusively in older patients. PATIENTS AND METHODS: We
      retrospectively analysed the prevalence of NPM1 and Flt3-ITD mutations and its
      association with complete remission (CR), and survival in 99 elderly patients
      (median age 71 yr, range 60-85 yr) newly diagnosed for AML. Primary treatment
      approach was curative in 54, and palliative in 38 patients, while seven patients
      received best supportive care only. The mean follow-up of surviving patients was
      600 d. RESULTS: Sixty-seven patients were tested negative for NPM1 and Flt3-ITD
      mutations (group 1), 16 patients carried only a NPM1 mutation (group 2) and nine
      patients had only a Flt3-ITD mutation (group 3) while additional seven patients
      were positive for both aberrations (group 4). We can demonstrate a significant
      higher rate of CR comparing wildtype vs. NPM1 positive patients (40.5% for group
      1 vs. 80.0% for group 2, P = 0.03) for patients receiving curative therapy.
      Interestingly, there is no significant difference in overall survival between
      group 1 and group 2 (Log-rank test P = 0.22, median 440 d vs. 1125 d). In
      contrast, patients carrying a Flt3-ITD mutation had a significant worse overall
      survival compared to wildtype patients (P = 0.03, median 210 d for group 3 + 4
      vs. 634 d for group 1 + 2) while no difference of CR rate could be observed
      (42.8% vs. 48.9%, P = 0.91). CONCLUSION: As elderly but medically fit patients
      with AML carrying a NPM1 mutation have a high CR rate, age itself should not be a
      barrier for induction treatment. However, new therapeutic concepts of
      postremission therapy (e.g. allogeneic stem cell transplantation after dose
      reduced conditioning) should be considered for these patients in first CR.

PMID- 18081720
TI  - Effective treatment and prophylaxis of hyperuricemia and impaired renal function
      in tumor lysis syndrome with low doses of rasburicase.
AB  - BACKGROUND: Tumor lysis syndrome (TLS) is a complication that can cause renal
      failure by precipitation of uric acid (UA) and phosphate crystals in renal
      tubules. Rasburicase proved to be effective in rapidly reducing UA levels. Costs
      of rasburicase average up to 4500 euros. To assess if lower doses of rasburicase
      are effective, we treated patients with lower doses than recommended. PATIENTS
      AND METHODS: Fifty patients received rasburicase for prophylaxis (n = 8) or
      treatment (n = 42) of TLS. The median age was 67 yr (16-88), 21 were female. The
      majority of patients (n = 46) had hematologic malignancies (acute leukemia, 14;
      lymphoma, 26; myeloproliferative/myelodysplastic syndromes, 6) and four had solid
      tumors. Creatinine levels were increased in 42 patients. RESULTS: Baseline median
      UA and creatinine levels were 856.5 micromol/L (339-1659.5 micromol/L) and 192.7
      micromol/L (65.4-761.1 micromol/L), respectively. Patients received between one
      and eight doses of rasburicase, the median total dose was 0.049 mg/kg. UA levels
      were lowered by 83%. After rasburicase treatment, median serum UA and creatinine
      levels were 160.6 micromol/L (5.9-779.2 micromol/L) and 111.4 micromol/L (46.9
      610 micromol/L), respectively. Treatment costs were reduced by 96.8%.
      CONCLUSIONS: Low doses of rasburicase are effective and cost-saving for
      prophylaxis and treatment of TLS. Application of an initial dose of 3-4.5 mg of
      rasburicase and subsequently dosage as needed, depending on UA levels, is
      feasible.

PMID- 18081721
TI  - Biological and clinical relevance of matrix metalloproteinases 2 and 9 in acute
      myeloid leukaemias and myelodysplastic syndromes.
AB  - We analysed by immunocytochemistry metalloproteinase (MMP)-2 and MMP-9 expression
      in bone marrow cells from 54 acute myeloid leukaemia (AML) patients, 153
      myelodysplastic syndrome (MDS) patients, and 52 non-haemopathic subjects, in
      order to evaluate whether MMP expression abnormalities were associated with
      relevant laboratory or clinical findings. In normal samples MMP-2 was detected in
      rare myeloid cells, MMP-9 in most maturing myeloid cells. In MDS MMP-2 myeloid
      levels were higher than in controls (P < 0.0001); MMP-2 and MMP-9 were often co
      expressed. Also many erythroblasts expressed MMP-2. There was a positive
      correlation between MMP-2 erythroblast expression and erythroid dysplasia (P =
      0.002) and an inverse correlation between MMP-2 or MMP-9 myeloid expression and
      blast cell percentage (P = 0.05 and P = 0.04 respectively). High MMP levels in
      myeloid cells were associated with longer overall survival (P = 0.03) and
      evolution-free survival (P = 0.04). In AML MMP-2 levels were lower than in MDS (P
      < 0.0001) and MMP-9 levels lower than in MDS and controls (P < 0.0001). MMP
      levels did not predict response to therapy. The release of active MMPs was
      detected by colorimetric analysis in cell cultures from representative MDS and
      AML cases. In conclusion, we have demonstrated an abnormal MMP expression in AML
      as well as in MDS. The production and release of these enzymes may influence
      haematopoietic cell behaviour. In MDS, the detection of MMP deregulated
      expression may be important also from the clinical point of view: it may provide
      a useful tool for diagnosis, prognosis and a possible target for experimental
      treatments.

PMID- 18081722
TI  - Non-invasive assessment of liver fibrosis by transient elastography in post
      transfusional iron overload.
AB  - BACKGROUND: Liver fibrosis, assessed by biopsy, is the main complication of post
      transfusional liver iron overload. Transient elastography (TE) is a new, non
      invasive method able to measure liver stiffness (LS) caused by fibrosis. METHOD:
      We prospectively evaluated the predictive value of LS measurement for liver
      fibrosis evaluation in 15 chronically transfused patients and compared these
      results with the METAVIR histological fibrosis stage from liver biopsies.
      RESULTS: Mean TE values significantly differed in patients with severe fibrosis
      (METAVIR F3, F4): 9.1 (+/-3.7 SD) kPa from those with mild or no fibrosis
      (METAVIR F0, F1, F2): 5.9 (+/-1.8 SD) kPa (P = 0.046). TE value above 6.25 kPa
      (Se = 80%; Sp = 70%; AUROC = 0.820) identified patients at risk for severe
      fibrosis (Negative Predictive Value 88%; Positive Predictive Value 57%).
      CONCLUSION: Transient elastography appears to be a reliable tool to evaluate
      liver fibrosis in post-transfusional iron overload.

PMID- 18081719
TI  - The heart in transfusion dependent homozygous thalassaemia today--prediction,
      prevention and management.
AB  - Cardiac disease remains the major cause of death in thalassaemia major. This
      review deals with the mechanisms involved in heart failure development, the
      peculiar clinical presentation of congestive heart failure and provides
      guidelines for diagnosis and management of the acute phase of cardiac failure. It
      emphasizes the need for intensive medical--cardiac care and aggressive iron
      chelating management as, with such approaches, today, the patients outcomes can
      be favourable in the long term. It covers advances in the assessment of cardiac
      iron overload with the use of magnetic resonance imaging and makes
      recommendations for preventing the onset of cardiac problems by tailoring iron
      chelation therapy appropriate to the degree of cardiac iron loading found.

PMID- 18081723
TI  - Association between promoter and coding region mutations of UDP
      glucuronosyltransferase 1A1 and beta-thalassemia/Hb E with cholelithiasis.
AB  - BACKGROUND AND OBJECTIVES: Cholelithiasis has been observed with high incidence
      in beta-thalassemia/hemoglobin E (beta-thal/Hb E). Recent studies have shown that
      a variant TATA-box in the promoter region of the UDP-glucuronosyltransferase 1A1
      (UGT1A1) gene is associated with the development of cholelithiasis. The coding
      region mutation (G71R) of the UGT1A1 gene was higher in Asians than those in
      Caucasians. The relationship between the variant UGT1A1 promoter and coding
      region gene and cholelithiasis in beta-thal/Hb E subjects were investigated.
      METHODS: One hundred and seventeen beta-thal/Hb E subjects entered this study.
      The TATA-box and G71R mutations were analyzed by fragment size analysis and
      restriction fragment length polymorphism methods, respectively. RESULTS: The
      incidence of cholelithiasis was higher in heterozygous (68.3%) and homozygous
      (100%) subjects compared with normal UGT1A1 haplotype (61.4%). Total bilirubin
      level (6.0 +/- 2.03 mg/dL) in the homozygous group was significantly higher than
      that of wild type (3.31 +/- 1.83 ng/dL). Prevalence of cholelithiasis increased
      with age (OR = 1.1, 95% CI = 1.03-1.12, P < 0.001). Female gender (OR = 3.7, 95%
      CI = 1.3-10.6, P < 0.01) and elevated liver enzyme (OR = 1.02, 95%CI = 1.0-1.04,
      P < 0.02) were two other risk factors for cholelithiasis in beta-thal/Hb E.
      CONCLUSION: This study shows that the combined TATA-box variants and G71R
      mutations of the UGT1A1 is associated with cholelithiasis in beta-thal/Hb E.

PMID- 18081724
TI  - Wilms tumour gene 1 overexpression in bone marrow as a marker for minimal
      residual disease in acute myeloid leukaemia.
AB  - OBJECTIVES: Wilms tumour gene 1 (WT1) is overexpressed in leucocytes of most
      acute myeloid leukaemia (AML) patients. However, the clinical relevance of WT1
      gene expression as minimal residual disease (MRD) marker in AML has been
      questioned. METHODS: We determined the expression of WT1 gene in bone marrow (BM)
      mononuclear cells of 100 AML patients at diagnosis and compared it with other MRD
      markers during follow up in 16 patients using quantitative reverse transcription
      polymerase chain reaction. RESULTS: The median WT1 gene expression was 9.7% of
      K562 cell line WT1 expression (lower quartile 1.5%, upper quartile 29.9%, n =
      100) at diagnosis and, 0.053% (lower quartile 0.022%, upper quartile 0.125%, n =
      87) in molecular or immunophenotypic remission. Median WT1 expression in control
      BM was 0.029% (lower quartile 0.013%, upper quartile 0.061%, n = 22). The upper
      99% percentile of remission samples was 0.3%, which was regarded as the cut-off
      of increased WT1 gene expression in AML and was exceeded in 87% of all AML
      patients at diagnosis. WT1 and the other MRD markers showed only minor
      differences in profiles during follow-up. WT1 expression at diagnosis with median
      value 9.7% as the cut-off level or as a continuous variable had no prognostic
      significance for 2-yr survival. CONCLUSIONS: The sensitivity of WT1 as a MRD
      marker was low due to the relatively high background WT1 gene expression in BM
      cells at remission and in subjects without haematological malignancies.
      Therefore, WT1 gene expression analysis would be beneficial only in those
      patients who do not have a more specific and sensitive MRD marker.

PMID- 18081725
TI  - The CEACAM1 transmembrane domain, but not the cytoplasmic domain, directs
      internalization of human pathogens via membrane microdomains.
AB  - Several bacterial pathogens exploit carcinoembryonic antigen-related cell
      adhesion molecules (CEACAMs) to promote attachment and uptake into eukaryotic
      host cells. The widely expressed isoform CEACAM1 is involved in cell-cell
      adhesion, regulation of cell proliferation, insulin homeostasis, and neo
      angiogenesis, processes that depend on the cytoplasmic domain of CEACAM1. By
      analysing the molecular requirements for CEACAM1-mediated internalization of
      bacteria, we surprisingly find that the CEACAM1 cytoplasmic domain is completely
      obsolete for bacterial uptake. Accordingly, CEACAM1-4L as well as a CEACAM1
      mutant with a complete deletion of the cytoplasmic domain (CEACAM1 DeltaCT)
      promote equivalent internalization of several human pathogens. CEACAM1-4L- and
      CEACAM1 DeltaCT-mediated uptake proceeds in the presence of inhibitors of actin
      microfilament dynamics, which is in contrast to CEACAM3-mediated internalization.
      Bacteria-engaged CEACAM1-4L and CEACAM1 DeltaCT, but not CEACAM3, localize to a
      gangliosid GM1- and GPI-anchored protein-containing portion of the plasma
      membrane. In addition, interference with cholesterol-rich membrane microdomains
      severely blocks bacterial uptake via CEACAM1-4L and CEACAM1 DeltaCT, but not
      CEACAM3. Similar to GPI-anchored CEACAM6, both CEACAM1-4L as well as CEACAM1
      DeltaCT partition into a low-density, Triton-insoluble membrane fraction upon
      receptor clustering, whereas CEACAM3 is not detected in this fraction. Bacterial
      uptake by truncated CEACAM1 or chimeric CEACAM1/CEACAM3 molecules reveals that
      the transmembrane domain of CEACAM1 is responsible for its association with
      membrane microdomains. Together, these data argue for a functional role of lipid
      rafts in CEACAM1-mediated endocytosis that is promoted by the transmembrane
      domain of the receptor and that might be relevant for CEACAM1 function in
      physiologic settings.

PMID- 18081726
TI  - Yersinia outer proteins: Yops.
AB  - The pathogenic bacteria Yersinia spp. contain a virulence plasmid that encodes a
      type III secretion system and effectors. During infection, four of the effectors
      target the actin cytoskeleton, crippling the phagocytic machinery in the infected
      cell. The remaining two effectors dampen the innate immune response by targeting
      important signalling pathways. Although the biochemical activity for each of
      these effectors is known, the mechanisms involved in their ordered secretion and
      delivery remain elusive.

PMID- 18081727
TI  - Early steps of the hepatitis C virus life cycle.
AB  - To replicate its genome, a virus needs to cross the plasma membrane of a host
      cell and get access to cytosolic and/or nuclear components. For an enveloped
      virus, this involves binding to the plasma membrane, followed by migration of the
      virion to a microdomain or an endosomal vesicle where fusion between the virion
      envelope and a host cell membrane occurs. Increasing evidences indicate that
      virus entry is a tightly regulated process. Although we are still far from
      understanding the details of hepatitis C virus (HCV) entry, recent data show that
      this virus enters into target cells in a slow and complex multistep process
      involving the presence of several entry factors. Initial attachment of the virion
      may involve glycosaminoglycans and the low-density lipoprotein receptor, and it
      is followed by the sequential interaction with the scavenger receptor class B
      type I, the tetraspanin CD81 and tight junction protein Claudin-1, -6 or -9.
      Furthermore, the identification of EWI-2wint as a new partner of CD81 which
      blocks E2-CD81 interaction provides additional evidence of the complexity of the
      HCV entry process. The current knowledge accumulated on HCV entry is summarized
      in this review.

PMID- 18081728
TI  - Serum retinol-binding protein 4 is not increased in obesity or obesity-associated
      type 2 diabetes mellitus, but is reduced after relevant reductions in body fat
      following gastric bypass.
AB  - OBJECTIVE: Controversy exists regarding the elevation of serum retinol-binding
      protein 4 (RBP4) in human obesity and type 2 diabetes mellitus (T2DM). In the
      present study, we have compared serum RBP4 in lean and obese patients with or
      without T2DM, and analysed the effect of weight loss on serum RBP4. DESIGN: Forty
      two Caucasian subjects were included in the study. Serum RBP4 was measured by
      ELISA and Western blot. In addition, serum RBP4 was measured in 21 morbidly obese
      patients before and after 4, 8 and 15 months of weight loss following Roux-en-Y
      gastric bypass (RYGBP). RESULTS: No significant effect of either obesity or
      diabetes on serum RBP4 was observed. Serum RBP4 concentrations (measured by
      either ELISA or Western blot) did not correlate with body mass index (BMI), body
      fat or any indicator of glucose metabolism or insulin resistance. Weight loss
      following RYGBP did not modify serum RBP4 at 15 months (P = 0.472). However, the
      variations in serum RBP4 were significantly associated with the reduction in body
      fat (r = 0.48; P = 0.026). Patients loosing over 20% of fat mass (n = 11) showed
      significantly different RBP4 concentrations compared to those individuals
      exhibiting smaller adiposity reductions (n = 10) (-11.0 +/- 6.4 vs.+5.8 +/- 3.6
      mg/l; P = 0.036). Furthermore, RBP4 levels were significantly reduced at 4 (P =
      0.006) and 8 (P = 0.015) months only in those patients loosing over 20% of fat
      mass. CONCLUSION: Serum RBP4 concentrations are not increased in obese patients
      with or without T2DM. A decrease in RBP4 levels was only observed after
      surgically induced weight loss accompanied by relevant reductions in body fat.
      RBP4 might be considered as a dynamic marker of negative energy balance being
      reduced during weight loss when a negative energy balance threshold is reached.
      Furthermore, RBP4 variation in the first month after RYGBP may be a predictor of
      weight loss success.

PMID- 18081729
TI  - Acid-related oesophageal sensitivity, not dysmotility, differentiates subgroups
      of patients with non-erosive reflux disease.
AB  - BACKGROUND: Patients with non-erosive reflux disease can experience reflux
      symptoms with similar frequency and severity as those with erosive reflux
      disease. Oesophageal motility and acid sensitivity are thought to influence
      symptom occurrence. AIM: To compare the effect of infused hydrochloric acid on
      oesophageal physiology in patients with non-erosive reflux disease and erosive
      reflux disease. METHODS: Twelve healthy controls and 39 patients with reflux
      disease [14 erosive reflux disease, 11 non-erosive reflux disease with normal
      (functional heartburn) and 14 non-erosive reflux disease with excess acid
      exposure] had hydrochloric acid and saline infused into distal and then proximal
      oesophagus. Oesophageal contraction amplitude, lower oesophageal sphincter
      pressure and pain intensity were documented at baseline and during each infusion.
      RESULTS: Patients with non-erosive reflux disease had higher pain sensitivity to
      acid than those with erosive reflux disease and controls. Proximal acid infusion
      caused greater pain than distal in patients with non-erosive reflux disease. Acid
      and saline sensitivity were more pronounced in patients with functional
      heartburn. Lower oesophageal sphincter pressure and oesophageal contraction
      amplitudes were lower in the erosive reflux disease and non-erosive reflux
      disease groups, but did not change during infusions. CONCLUSIONS: Patients with
      non-erosive reflux disease and, to a lesser extent, patients with erosive reflux
      disease, are sensitive to acid in the oesophagus, being more sensitive to
      proximal acid. Hypersensitivity is most marked in functional heartburn patients.
      This acid sensitivity is not associated with motility change.

PMID- 18081730
TI  - The use of adalimumab in the management of refractory Crohn's disease.
AB  - BACKGROUND: Adalimumab is a humanized monoclonal antibody targeting tumour
      necrosis factor-alpha. Recent clinical trials have demonstrated its efficacy in
      Crohn's disease; however, experience in clinical practice remains limited. AIM:
      To investigate the efficacy and safety of adalimumab in the clinical setting.
      METHODS: The clinical outcomes of patients with medically refractory Crohn's
      disease treated with adalimumab in the Western General Hospital Edinburgh, over a
      3-year period (2003-2006), were studied. RESULTS: Twenty-two (14 females; age at
      therapy: 32.6 years) patients were treated using an 80/40 mg induction regimen
      followed by fortnightly 40 mg treatment. All had proven refractory/intolerant to
      corticosteroids and immunosuppression. Twenty patients had had previous
      infliximab infusions - of these eight (36%), six (27%), three (14%) had previous
      infusion reactions, no response and lost response to infliximab, respectively.
      Over a period of 1.0 years (IQR: 0.62-2.5), Kaplan-Meier analyses showed that 68%
      (seven nonresponders) were in clinical remission and 67% (five surgery -
      discounting oral CD) avoided further surgery for active disease. 59% required
      dose escalation to 40 mg weekly (0.55 years; IQR: 0.22-1.4). Three (50%) primary
      nonresponders to infliximab achieved remission. Two patients developed serious
      infective complications and one patient developed lung cancer. CONCLUSIONS:
      Adalimumab is efficacious in refractory Crohn's disease, with benefit observed in
      infliximab primary nonresponders. However, many patients require escalation of
      dosing regimen.

PMID- 18081731
TI  - Transient elastography to assess hepatic fibrosis in primary biliary cirrhosis.
AB  - BACKGROUND: Liver stiffness measurements may have potential for detecting and
      monitoring hepatic fibrosis in chronic liver disease. AIM: To study the
      detection, quantification and progression of hepatic fibrosis in primary biliary
      cirrhosis by liver stiffness measurements. METHODS: Liver stiffness measurements
      were generated in 80 patients with primary biliary cirrhosis by applying
      transient elastography; however, as there were 55 with liver biopsy, histological
      stage (METAVIR) and liver stiffness measurements were compared only in these 55
      patients. The efficiency of liver stiffness measurements in predicting stage of
      fibrosis was determined from the area under receiver operating characteristics
      curve analysis. RESULTS: Of the 80 patients included, 91, 4% were women and their
      mean age was 56 +/- 12 (s.d.) years. A significant correlation was found (P <
      0.05) between histological fibrosis stage (METAVIR) and liver stiffness
      measurements. The values obtained from area under receiver operating
      characteristic curve analysis of liver stiffness measurement data were 0.89 for F
      > 2 and 0.96 for F = 4. Liver stiffness measurements were 9.0 +/- 5.3 and 7.9 +/-
      6.0 kPa for patients followed up more than 5 years and less than 5 years,
      respectively (P > 0.05). CONCLUSIONS: In patients with primary biliary cirrhosis,
      median values of liver stiffness measurements correlated with histological
      severity of hepatic fibrosis. Liver stiffness measurements appear to be promising
      for liver fibrosis detection and quantification, as well as monitoring its
      progression, in patients with primary biliary cirrhosis. The progression rate of
      hepatic fibrosis in our primary biliary cirrhosis patients appears to be slow.

PMID- 18081732
TI  - A novel partial 5HT3 agonist DDP733 after a standard refluxogenic meal reduces
      reflux events: a randomized, double-blind, placebo-controlled pharmacodynamic
      study.
AB  - BACKGROUND: DDP733, a selective partial 5HT(3) receptor agonist, increases lower
      oesophageal sphincter pressure in experimental animal models. However, its effect
      on gastro-oesophageal reflux or lower oesophageal sphincter pressure in humans
      remains unknown. AIM: To evaluate the effect of DDP733 on reflux episodes in
      healthy volunteers receiving a refluxogenic meal. METHODS: A randomized, double
      blind, placebo-controlled cross-over study evaluated the pharmacodynamic effects
      of DDP733 (0.5, 0.8 and 1.4 mg). Healthy subjects underwent oesophageal manometry
      and intra-oesophageal multichannel intraluminal impedance and pH after a
      refluxogenic meal. RESULTS: DDP733 0.5 mg significantly (P = 0.013) reduced the
      rate of reflux episodes after a refluxogenic meal from 10 (+/-2.2) on placebo to
      6 (+/-1.2) on drug over a 2-h period. DDP733 0.8 and 1.4 mg had no significant
      effect on reducing the number of reflux episodes. Significant differences in
      resting lower oesophageal sphincter pressure and the proportion of time pH was <4
      (placebo minus drug) after a refluxogenic meal were not observed. No serious
      adverse events were reported. CONCLUSION: In healthy subjects, the partial 5HT(3)
      agonist DDP733 at a dose of 0.5 mg significantly reduces the rate of reflux
      events, but did not result in a significant change in lower oesophageal sphincter
      pressure at 1 h postdosing.

PMID- 18081733
TI  - Clinical trial: interferon alpha-2b continuous long-term therapy vs. repeated 24
      week cycles for re-treating chronic hepatitis C.
AB  - BACKGROUND: Treatment options are limited for patients with hepatitis C virus who
      do not experience sustained viral eradication with pegylated interferon and
      ribavirin therapy. AIM: To compare, in an open-label, randomized study, long-term
      continuous interferon alpha-2b treatment with repeated 24-week courses in
      patients with chronic hepatitis C virus that relapsed after prior interferon
      monotherapy. METHODS: A total of 499 patients received 24 weeks of interferon
      alpha-2b, 3 MIU administered 3 TIW. Responders (normal alanine aminotransferase
      and negative hepatitis C virus -RNA, n = 244) were then randomized to continuous
      interferon therapy (1, 2 or 3 MIU TIW depending on response) or cyclical therapy
      (3 MIU TIW for 24 weeks per relapse). Mean Knodell inflammation (I + II + III)
      and necrosis (IV) scores at baseline vs. year 2 were compared. RESULTS: Patients
      receiving continuous low-dose therapy vs. cycled therapy had larger reductions in
      inflammation (-3.9 vs. -3.1) and fibrosis (-0.49 vs. -0.24). Among both groups,
      the mean change was -3.4 for inflammation and -0.36 for fibrosis. Overall, 73%
      (95% CI: 67-79) of patients experienced reduced inflammation and 28% (95% CI: 22
      34) had reduced fibrosis. CONCLUSIONS: Our results suggest hepatitis C virus
      patients experiencing viral suppression during long-term maintenance therapy with
      interferon demonstrate histological improvement. Further prospective trials
      testing this hypothesis are in progress.

PMID- 18081734
TI  - Serum resistin is positively correlated with the accumulation of metabolic
      syndrome factors in type 2 diabetes.
AB  - OBJECTIVE: Resistin, secreted from adipocytes, causes insulin resistance in
      rodents. We reported that the G/G genotype of a resistin gene promoter single
      nucleotide polymorphism (SNP) at -420 increases type 2 diabetes (T2DM)
      susceptibility by enhancing promoter activity. We also showed that serum resistin
      was positively correlated with G at SNP-420, the duration of T2DM, and HbA1c in
      T2DM. The aim of this study was to determine the relation between serum resistin
      and factors related to the metabolic syndrome (MetS) in T2DM. DESIGN, PATIENTS
      AND MEASUREMENTS: We analysed 238 Japanese T2DM subjects (124 males and 114
      females, age 60.2 +/- 11.3 years, body mass index (BMI) 24.1 +/- 3.9) whose
      overnight fasting sera were available. Serum resistin was measured using ELISA.
      RESULTS: Serum resistin was higher in subjects with either obesity (P = 0.041),
      low HDL (P = 0.004), high triglycerides (TG) (P = 0.019), hypertension (HT) (P =
      0.001) or atherosclerosis (P = 0.012). Simple regression analysis revealed that
      serum resistin was correlated with lower HDL, TG and high-sensitivity C-reactive
      protein (hsCRP). Multiple regression analysis (or logistic regression analysis
      for HT), adjusted for age, gender, BMI and the duration of T2DM, revealed that
      serum resistin was correlated with lower HDL (P = 0.008), TG (P = 0.041), HT (P =
      0.031) and hsCRP (P = 0.004). Serum resistin was positively correlated with the
      number of MetS factors, independent of age, gender and the duration of T2DM (P <
      0.001). Adjustment by either thiazolidinedione (TZD) treatment or hsCRP had no
      effects on these findings. CONCLUSIONS: Serum resistin was positively correlated
      with the accumulation of MetS factors in T2DM.

PMID- 18081736
TI  - Baseline microbiota activity and initial bifidobacteria counts influence
      responses to prebiotic dosing in healthy subjects.
AB  - BACKGROUND: Dietary intervention with prebiotics can cause changes in the colonic
      microbiota and their metabolic activities. AIM: To investigate whether the
      response to prebiotic dosing is influenced by the baseline metabolic activity of
      the colonic flora and bifidobacteria counts. METHODS: The 4-week effect of
      lactulose (10 g bid.; n = 29) and oligofructose-enriched inulin (10 g bid.; n =
      19) was evaluated in healthy human volunteers. Lactose-[(15)N, (15)N]-ureide was
      used to study the colonic NH(3)-metabolism. Urine (48 h) and faeces (72 h) were
      collected and analysed for p-cresol and (15)N-content by gas chromatography-mass
      spectrometry and isotope ratio mass spectrometer, respectively. Faecal
      bifidobacteria were quantified by real-time polymerase chain reaction. RESULTS:
      After the 4-week prebiotic administration period, the urinary excretion of p
      cresol and (15)N was significantly decreased in both groups (P < 0.05)
      corresponding to a significantly higher faecal excretion of (15)N (P < 0.05). The
      decrease in urinary (15)N and p-cresol excretion significantly correlated with
      baseline (15)N and p-cresol levels (P < 0.05), indicating that subjects with
      higher baseline levels showed a higher response to prebiotic dosing. Furthermore,
      a significant correlation was seen between baseline bifidobacteria counts and the
      effect of prebiotic intake (P < 0.05). CONCLUSION: The response to prebiotic
      dosing, as indicated by the fate of NH(3), p-cresol and bifidobacteria, is
      determined by the initial colonic conditions.

PMID- 18081735
TI  - Factors predicting survival in patients with advanced oesophageal cancer: a
      prospective multicentre evaluation.
AB  - BACKGROUND: Oesophageal cancer is often diagnosed at an advanced stage, with poor
      prognosis and severe morbidity. In majority of cases, palliative treatment is the
      only option available. AIM: To find factors that can predict survival for
      patients with incurable cancer of the oesophagus or gastro-oesophageal junction
      and hence aid in the choice of treatment. METHODS: Ninety-six patients were
      included. Health-related quality of life questionnaires (EORTC QLQ C-30 and QLQ
      OES18) were administered and computerized tomography-derived size assessment of
      the primary tumours was performed. Univariate and multivariate Cox-regression
      analyses were used to determine potential predictors of survival. RESULTS:
      Karnofsky Index, occurrence of metastases (M-stage), Union International Contre
      le Cancer-stage, computerized tomography-derived tumour size assessment and 10 of
      25 scales and single items from the health-related quality of life questionnaires
      were found to be related to survival. In the multivariate analysis, three of the
      health-related quality of life questionnaire scales (physical functioning,
      fatigue and reflux) were found to add prognostic information to M-stage, the
      single strongest predictor (HR 1.9, P < 0.01). CONCLUSION: In addition to M
      stage, the outcome of health-related quality of life questionnaires can sharpen
      the prediction of survival in patients with advanced cancer of the oesophagus or
      gastro-oesophageal junction and thus aid in the choice of palliative treatment
      strategy.

PMID- 18081737
TI  - Peginterferon alfa-2a/ribavirin in hepatitis C virus patients nontolerant or
      nonresponsive to peginterferon alfa-2b/ribavirin.
AB  - BACKGROUND: Peginterferon alfa-2a/ribavirin treatment resulted in fewer
      incidences of depression and flu-like symptoms than that of standard
      interferon/ribavirin, whereas peginterferon alfa-2b/ribavirin and standard
      interferon/ribavirin treatment resulted in similar incidences of these adverse
      events (AEs). AIM: To assess the efficacy and safety of peginterferon alfa
      2a/ribavirin in genotype 1-infected patients treated for up to 12 weeks with
      peginterferon alfa-2b/ribavirin but not achieving early virologic response (EVR)
      (non-EVR) or nontolerant (NT) because of depression, fatigue, flu-like symptoms,
      or injection-site reactions. METHODS: Nontolerants were treated for an additional
      36 weeks and non-EVRs for an additional 60 weeks with peginterferon alfa-2a (180
      microg/week)/ribavirin (1000/1200 mg/day). Patients with detectable HCV RNA after
      12 weeks were discontinued. RESULTS: Of 25 NTs, 23 (92%) were HCV-RNA negative
      after 12 weeks on peginterferon alfa-2a/ribavirin and 14 (56%) achieved sustained
      virologic response. Of 32 non-EVRs to peginterferon alfa-2b/ribavirin, four (13%)
      achieved EVR with peginterferon alfa-2a/ribavirin and one (3%) achieved sustained
      virologic response. Four non-EVRs and 0 NTs were withdrawn for AEs; 26 (81%) and
      24 (96%), respectively, completed peginterferon alfa-2a/ribavirin treatment or
      were withdrawn for insufficient response at week 12. In NTs, depression, fatigue,
      flu-like symptoms, and injection-site reactions declined during treatment.
      CONCLUSION: Most patients who did not tolerate peginterferon alfa-2b/ribavirin
      because of AEs, and who completed the full 36-week course of peginterferon alfa
      2a/ribavirin treatment, achieved sustained virologic response.

PMID- 18081738
TI  - Adipokines and cytokines in non-alcoholic fatty liver disease.
AB  - BACKGROUND: Several adipocytokines have been implicated in the pathogenesis non
      alcoholic fatty liver disease (NAFLD). AIM: To assess adipocytokines in NAFLD
      patients and controls. METHODS: A total of 95 patients (26 non-alcoholic
      steatohepatitis (NASH), 19 simple steatosis (SS), 38 obese controls and 12 non
      obese controls) were included. Fasting serum insulin, glucose, visfatin,
      resistin, adiponectin, tumour necrosis factor-alpha (TNF-alpha), interleukin-8
      (IL-8) and IL-6 were determined. Univariate and multivariate analyses were used
      to compare groups and determine associations. RESULTS: Serum TNF-alpha and IL-8
      were higher in NAFLD patients when compared with both obese and non-obese
      controls. Analysis involving all patients revealed a significant correlation
      between serum TNF-alpha and IL-8 (P < 6.319e-08), and between IL-6 and IL-8 (P <
      5.271e-15). Homeostatic model assessment scores negatively correlated with
      adiponectin in NAFLD (P < 0.0032). Serum visfatin was higher in all three obese
      groups than in non-obese controls (P < 0.02, P < 0.002 and P < 0.008). Visfatin
      in NASH patients was lower than SS and obese controls. Although TNF-alpha was
      associated with NAFLD (P < 0.02), it was interdependent on visfatin. In
      comparison to SS, four factors were independently associated with NASH: age,
      alanine aminotransferase, IL-8 and adiponectin (P < 0.05). Multivariate analysis
      indicated that TNF-alpha was the only independent predictor of fibrosis in NASH
      (P < 0.0004). CONCLUSION: These findings support a complex interaction between
      adipocytokines and the pathogenesis of NAFLD.

PMID- 18081739
TI  - Effect of aerobic training on 99mTc-methoxy isobutyl isonitrile (99mTc-sestamibi)
      uptake by myocardium and skeletal muscle: implication for noninvasive assessment
      of muscle metabolic profile.
AB  - AIM: The effect of long-term endurance training on skeletal muscle and myocardial
      uptake of (99m)Tc-sestamibi, a radiopharmaceutical accumulating in the
      mitochondria, was investigated. METHODS: Twenty-six Wistar rats were divided into
      a trained (5 days week(-1) endurance running for 14 weeks) and an untrained
      group. On completion of training, (99m)Tc-sestamibi was administered and, 2 h
      post-injection, the myocardium and the soleus, extensor digitorum longus (EDL)
      and medial gastrocnemius (MG) muscles were removed for the measurement of
      cytochrome c oxidase (CCO) activity and (99m)Tc-sestamibi uptake. Tissue (99m)Tc
      sestamibi kinetics was preliminarily studied in 16 other rats for up to 2 h post
      injection. RESULTS: Two hours post-injection (99m)Tc-sestamibi uptake was either
      stable (myocardium) or still rising (skeletal muscles). Both CCO activity and
      (99m)Tc-sestamibi uptake decreased in the same order (myocardium, soleus, EDL,
      MG) in the tissues examined. The CCO activity of the EDL and MG muscles was
      higher (P < 0.05) in the trained compared to the untrained group. (99m)Tc
      sestamibi uptake in the soleus and EDL muscles was higher (P < 0.05) in the
      trained compared to the untrained rats, whereas the difference in MG was
      marginally significant (P = 0.06) in favour of the trained group. CONCLUSIONS:
      Long-term endurance training, resulting in elevated skeletal muscle CCO activity,
      is also associated with a similar increase in (99m)Tc-sestamibi uptake. This
      finding suggests that (99m)Tc-sestamibi could be used in imaging assessment of
      skeletal muscle metabolism with possible applications in both clinical and sports
      medicine settings.

PMID- 18081740
TI  - Angiotensin II-induced contractions in human jejunal wall musculature in vitro.
AB  - AIM: Angiotensin II is well known for its contractile effects on smooth muscle
      cells. This effect is also present in the gut previously shown in animal models.
      The aim of this study was to clarify expression and localization of angiotensin
      II receptors in the human small intestine and to explore the pharmacological
      profile of angiotensin II effects in vitro. METHODS: Strips of jejunal muscle
      wall from 32 patients undergoing bariatric surgery were used to record isometric
      tension in vitro in response to angiotensin II (10(-10)-10(-5) M) alone and in
      the presence of PD123319 (10(-7) M), losartan (10(-7) M), PD123319 (10(-7) M) and
      losartan (10(-7) M) in combination, tetrodotoxin (TTX) (10(-6) M), atropine (10(
      6) M) and guanethidine (3 x 10(-6) M). Western blot, immunohistochemistry and RT
      PCR were performed on corresponding muscle samples to identify expression and
      localization of key components of the renin-angiotensin system. RESULTS:
      Angiotensin II elicited concentration-dependent contraction in both longitudinal
      and circular jejunal muscle wall strips; neither TTX, atropine nor guanethidine
      affected this action. Losartan alone and in combination with PD123319 shifted the
      concentration-response curve to the right. Transcription of angiotensinogen, ACE
      and angiotensin II types 1 and 2 receptor RNA was detected in all patients.
      Immunohistochemistry detected angiotensin II type 1 receptors in the musculature;
      both angiotensin II types 1 and type 2 receptors were found in the myenteric
      plexus. CONCLUSION: This pharmacological analysis indicates that the contractile
      action elicited by angiotensin II on jejunal wall musculature is primarily
      mediated through the angiotensin II type 1 receptor located on the musculature.

PMID- 18081741
TI  - Disrupted intracellular calcium regulates BACE1 gene expression via nuclear
      factor of activated T cells 1 (NFAT 1) signaling.
AB  - Beta-site APP-cleaving enzyme 1 (BACE1) expression is elevated in the brains of
      Alzheimer's disease (AD) patients and in aged-animal models. Because both AD and
      aging are associated with disrupted calcium homeostasis, we investigated the role
      of nuclear factor of activated T cells (NFAT) - a transcription factor regulated
      by the calcium- and calmodulin-dependent phosphatase calcineurin - in BACE1
      expression. BACE1 expression was stimulated by a calcium ionophore in primary
      cortical cultures, and by SH-SY5Y neuroblastoma cells, which was both blocked by
      pretreatment with either cyclosporin A, an inhibitor of calcineurin, or
      ethyleneglycotetraacetic acid, a calcium chelator. Gel shift assays revealed
      direct binding of NFAT1 to specific DNA sequences within the BACE1 gene promoter
      region. Treatment with amyloid beta (Abeta), one of the major factors in AD
      pathogenesis, stimulated activation and nuclear translocation of NFAT1 following
      up-regulation of BACE1 expression. In addition, primary cortical cultures from
      Tg2576 mouse brains generated more Abeta by ionophore stimulation, which was
      reversed by cyclosporin A treatment. Furthermore, NFAT1 activation was observed
      in Tg2576 mouse brains. These results suggest that calcium ionophore- or Abeta
      induced increases in intracellular calcium concentration stimulate BACE1
      expression, resulting in accelerated Abeta generation, and that this process is
      mediated through the calcineurin-NFAT1 signaling pathway. This process may play a
      significant role in the pathogenesis of AD and aging.

PMID- 18081742
TI  - Elevated Ras/protein kinase A activity in Saccharomyces cerevisiae reduces
      proliferation rate and lifespan by two different reactive oxygen species
      dependent routes.
AB  - Cells with overactive RAS/protein kinase A (PKA) signaling, such as RAS2(Val19)
      cells, exhibit reduced proliferation rates and accelerated replicative
      senescence. We show here that the extended generation time of RAS2(Val19)cells is
      the result of abrogated ATP/ADP carrier activity of the mitochondria. Both PKA
      dependent and independent routes are responsible for inhibiting ATP/ADP exchange
      in the RAS-overactive cells. The reduced carrier activity is due, at least in
      part, to elevated levels of reactive oxygen species (ROS), which also cause a
      proteolysis-dependent fragmentation of the Aac2p carrier both in vivo and on
      isolated mitochondria. Attenuated carrier activity is suppressed by overproducing
      the superoxide dismutase, Sod1p, and this enhances both the proliferation rate
      and the replicative longevity of RAS2(Val19) cells. In contrast, overproducing
      functional Aac2p restored proliferation but not longevity of RAS2(Val19) cells.
      Thus, Ras signaling affects proliferation rate and replicative lifespan by two
      different, ROS-dependent, routes. While the reduction in generation time is
      linked to the inactivation, specifically, of the mitochondrial nucleotide
      carrier, longevity is affected by other, and hitherto unknown, target(s) of ROS
      attack.

PMID- 18081743
TI  - One big, and many small reasons that direct selection on offspring number is
      still open for discussion.
AB  - In a recent paper, I proposed that natural selection should act to increase
      offspring number when diversification bet hedging is favoured. The simple
      underlying reasoning is that a target diversification strategy is more reliably
      generated with increasing sample size. The intention of opening a discussion has
      been realized; recent criticisms of the idea argue that selection does not act to
      increase offspring number when population size is large or infinite. Here I agree
      that criticisms have merit; indeed they are largely confined to the caveats
      discussed in my original paper. The critique, however, implies a verdict of
      outright rejection of the idea of selection on offspring number, which would be
      erroneous. Contrary to the assertions of the criticism, then, the importance of
      selection acting directly on offspring number remains an open question.

PMID- 18081744
TI  - Wing morphology and fluctuating asymmetry depend on the host plant in cactophilic
      Drosophila.
AB  - As in most insect groups, host plant shifts in cactophilic Drosophila represent
      environmental challenges as flies must adjust their developmental programme to
      the presence of different chemical compounds and/or to a microflora that may
      differ in the diversity and abundance of yeasts and bacteria. In this context,
      wing morphology provides an excellent opportunity to investigate the factors that
      may induce changes during development. In this work, we investigated phenotypic
      plasticity and developmental instability of wing morphology in flies on the
      cactophilic Drosophila buzzatii and Drosophila koepferae raised on alternative
      breeding substrates. We detected significant differences in wing size between and
      within species, and between flies reared on different cactus hosts. However,
      differences in wing shape between flies emerged from different cactus hosts were
      not significant either in D. buzzatii or in D. koepferae. Our results also showed
      that morphological responses involved the entire organ, as variation in size and
      shape correlated between different portions of the wing. Finally, we studied the
      effect of the rearing cactus host on developmental instability as measured by the
      degree of fluctuating asymmetry (FA). Levels of FA in wing size were
      significantly greater in flies of both species reared in non-preferred when
      compared with those reared in preferred host cacti. Our results are discussed in
      the framework of an integrative view aimed at investigating the relevance of host
      plant shifts in the evolution of the guild of cactophilic Drosophila species that
      diversified in South America.

PMID- 18081745
TI  - Decay of unused characters by selection and drift.
AB  - The reduction and loss of redundant phenotypic characters is a common feature of
      evolution. However, the mechanisms that drive deterioration of unused characters
      remain unclear. Here, we outline a simple framework where the relative importance
      of selective and neutral processes varies with environmental factors, because of
      variation in the fitness costs associated with unused traits. We tested our
      hypotheses using experimental evolution of the bacterium Pseudomonas fluorescens
      in spatially uniform environments. Results show that an unused character,
      swimming motility, decayed over evolutionary time and the rate of this decay
      varied among selection environments with different levels of resource
      availability. This is explained in the context of an environment-specific genetic
      correlation between motility and fitness, which is negative when resources are
      limited but neutral at higher resource levels. Thus, selection against an unused
      character was most effective in environments where the fitness cost was the
      greatest. This suggests that the same character can decay by different mechanisms
      depending upon environmental factors and supports previous evidence to show that
      resource availability can critically affect the outcomes of evolution.

PMID- 18081746
TI  - Cryptic diversification in ancient asexuals: evidence from the bdelloid rotifer
      Philodina flaviceps.
AB  - Bdelloid rotifers, darwinulid ostracods and some oribatid mites have been called
      'ancient asexuals' as they speciated and survived over long-term evolutionary
      timescale without sexual recombination. Data on their genetic diversification are
      contrasting: within-species diversification is present mostly at a continental
      scale in a parthenogenetic oribatid mite, whereas almost no genetic
      diversification at all seems to occur within darwinulid ostracod species.
      Strangely enough, no clear data for bdelloid rotifers are available so far. In
      this paper, we analyse partial COI mtDNA sequences to show that a bdelloid
      rotifer, Philodina flaviceps, so far considered a single traditional
      morphological species, has actually been able to diversify into at least nine
      distinct evolutionary entities, with genetic distances between lineages
      comparable with those between different traditional species within the same
      genus. We discovered that local coexistence of such different independent
      lineages is very common: up to four lineages were found in a same stream, and up
      to three in a single moss sample of 5 cm(2). In contrast to the large-scale
      geographic pattern that has recently been reported in the oribatid mite, the
      spatial distribution of the bdelloid lineages provided evidence of micro
      phylogeographic patterns. If the mtDNA diversity indicates that the lineages are
      independent and represent sympatric cryptic species within P. flaviceps, then the
      actual bdelloid diversity can be expected to be much greater than that recognized
      today.

PMID- 18081747
TI  - Efficacy and safety of desloratadine combined with dipyridamole in the treatment
      of chronic urticaria.
AB  - Chronic urticaria (CU) imposes profound impairment on patient's quality of life.
      Our study was done to evaluate the clinical efficacy and safety of desloratadine
      combined with dipyridamole, which is a platelet adhesion inhibitor in the
      treatment of CU. A randomized study was done in 64 autoimmunity CU patients with
      positive autologous plasma skin test (APST): 34 patients as treatment and 30
      controls. The treatment group was treated with desloratadine and dipyridamole,
      and the control group was treated with desloratadine only. The efficiency and
      side-effect were evaluated at the end of treatment. The levels of fragment F(1+2)
      were measured by enzyme-linked immunosorbent assay in all patients at pre- and
      post-treatment. The clinical effectiveness rates of treatment and control group
      were, respectively, 85.20% (21 cured, 8 obvious effectiveness) and 70% (14 cured,
      7 obvious effectiveness); they have a significant difference (x = 4.09, P <
      0.05). Before treatment, the weals and pruritus in the treatment and control
      group were, respectively, (1.74 +/- 0.90, 1.79 +/- 0.73) and (1.67 +/- 0.84, 1.73
      +/- 0.78). After treatment, the weals and pruritus in treatment and control group
      were, respectively, (0.38 +/- 0.73, 0.58 +/- 0.89) and (0.67 +/- 0.96, 1.10 +/-
      1.12). These findings provide new insights into the pathogenesis of CU and
      suggest new therapeutic opportunities for treating this disease.

PMID- 18081748
TI  - Psoriasis: consensus on topical therapies.
AB  - OBJECTIVE: A consensus conference was convened to evaluate the topical treatment
      of psoriasis. PARTICIPANTS: Members of the International Psoriasis Council (IPC)
      with broad clinical experience in the treatment of psoriasis and a specialist in
      meta- and pharmacoeconomic analyses were invited to participate on the consensus
      panel. Those accepting the invitation convened in Saariselka, Finland. EVIDENCE:
      An advisory group on topical treatments was nominated by the organizing panel
      members. All participants reported at the consensus conference on evidence based
      data with respect to disease severity assessment, the available data on efficacy
      and safety and on a comparative efficacy/safety analysis. CONSENSUS PROCESS: At
      the consensus conference, the presentations were discussed and conclusions, which
      were reached by the group, were recorded. Active participants of the group wrote
      assigned sections of this consensus document with a majority of participants
      agreed on the conclusions.

PMID- 18081749
TI  - A generalized skin eruption in a human immunodeficiency virus-infected boy.

PMID- 18081750
TI  - Repigmentation of the white hair after systemic corticosteroids for bullous
      pemphigoid.

PMID- 18081751
TI  - Thick melanoma: the problem continues.
AB  - BACKGROUND: The incidence of melanoma and its associated mortality has stabilized
      over the recent years, due in part to efforts directed at better prevention and
      detection of these lesions. We analysed the trends in the distribution of
      melanomas, mainly according to their thickness. METHODS: Data from the
      Dermatology Service of 'Virgen de la Victoria' University Hospital in Malaga
      (Spain) showed a total of 459 cases of melanoma between 1990 and 2005, both
      inclusive. The lesions were stratified according to year of diagnosis (1990-96
      and 1997-2005), sex, age (0-49, > or = 50), thickness (0-0.99, 1.00-1.99, and >
      or = 2 mm) and the histological subtype [lentigo maligna melanoma (LMM),
      superficial spreading melanoma (SSM), nodular melanoma (NM) and acral lentiginous
      melanoma (ALM)]. Particular attention was given to the distribution of the groups
      according to thickness. RESULTS: The number of new cases rose by 92% between the
      two study periods (1990-1996 and 1997-2005). However, the number of new cases of
      thick melanoma remained almost constant over the two periods, being associated
      with persons over 50 years of age (65.1% vs. 64.3%), with men having half the
      cases (48.4% vs. 47%). The proportion of nodular melanomas within the group of
      thick melanomas was high in both periods (36.5% and 39.3%, respectively).
      CONCLUSIONS: This study shows that despite the large increase in new melanomas,
      the diagnosis of thick melanomas has remained constant, mainly in persons over
      the age 50 years, with a relative increase in men. New strategies and education
      programmes are, therefore, required for the early detection of this type of
      tumour to reduce its incidence in these patients.

PMID- 18081752
TI  - The effects of skin colour distribution and topography cues on the perception of
      female facial age and health.
AB  - According to evolutionary psychology, the preference for some facial
      characteristics reflects adaptations for mate choice because they signal aspects
      of mate quality. Although morphological features such as facial symmetry and
      sexually dimorphic traits have been studied extensively in recent years, little
      is known about skin condition in this context. The preferences for young and
      healthy looking skin could offer an explanation as to why women place such an
      importance on the condition of their skin and its refinement through e.g.,
      cosmetic products. Recent research showed that facial skin colour distribution
      significantly influences the perception of age and attractiveness of female
      faces, independent of skin surface topography cues. However, the relative effect
      of skin colour distribution and topography cues on age and health perception
      remains to be investigated. We present data showing that both skin colour
      distribution and skin surface topography cues not only significantly influence
      the perception of female facial age and health but also convey differential
      information with regard to the strength of these effects. Our data indicate that
      skin surface topography cues account for a large proportion of variation in
      facial age perception, whereas skin colour distribution seems to be a stronger
      health cue.

PMID- 18081753
TI  - Prospective randomized non-blinded clinical trial on the use of dapsone plus
      antihistamine vs. antihistamine in patients with chronic idiopathic urticaria.
AB  - BACKGROUND: Treatment of chronic idiopathic urticaria (CIU) is difficult.
      OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of
      dapsone in CIU. METHODS: The response to dapsone was evaluated in 65 CIU patients
      with a randomized, two armed study: 3-month dapsone + desloratadin and 3-month
      desloratadin. All were followed for up to 3 months and 3 months after; all took
      desloratadine 10 mg daily throughout the study. The primary measure of efficacy
      was a daily urticaria activity score (UAS) of weal numbers and itch (maximum
      score, 42 per week). RESULTS: Sixty-five patients completed the randomized 3
      month trial medication. Mean reduction in UAS from baseline at 3 months was 7
      [95% confidence interval (95% CI), 6.92-7.08] for active group and 5.77 (95% CI,
      5.47-6.08) for control subjects (P < 0.001). The reduction in visual analogue
      score (VAS) at 3 months for active group (mean, 2.58; 95% CI, 2.33-2.83) and
      control subjects (mean, 2.55; 95% CI, 2.38-2.73) was also significant (P <
      0.001). The reduction of UAS and VAS at 3 months compared between active group
      and control subjects showed no significant difference. Mean reduction in UAS from
      the end of the study at 3 months after was 1.16 and -4.8 for active and control
      subjects, respectively. These results were compared with each other, and it was
      statistically significant (P <or= 0.05). LIMITATIONS: No placebo was used. The
      study was not blinded. Lack of blinding may have led to bias. The follow-up
      period was short. CONCLUSION: This study shows that dapsone leads to a persistent
      decrease in VAS and UAS and is associated with complete remission in some
      patients.

PMID- 18081754
TI  - New lifestyle drugs and somatoform disorders in dermatology.
AB  - An increasing number of healthy individuals make use of 'lifestyle' drugs, such
      as nootropics, psychopharmaca, hormones and eco-drugs. In this respect, the fact
      that many people try to improve their outer appearance, solve their 'cosmetic
      problems', influence their rate of hair growth and altogether delay, halt or even
      reverse the natural ageing process has become a relevant matter for the
      practising dermatologist. Lifestyle drugs in dermatology are taken in an attempt
      to increase personal life quality by means of attaining a certain, psychosocially
      defined beauty ideal. They are not taken to manage a medically identifiable, well
      defined disease. Often, patients suffering from somatoform disorders, such as
      hypochondriac disorders, body dysmorphic disorders, somatization disorders or
      persistent somatoform pain disorders, may spontaneously ask physicians, in
      particular dermatologists and plastic surgeons, to prescribe them lifestyle
      drugs. Typically, patients repeatedly present with alleged 'physical symptoms'
      that turn out to be subjective complaints without any underlying identifiable
      medical disease. The use of lifestyle drugs without any proper medical indication
      may lead to a chronification of the emotional disorders that had ultimately been
      the cause of the patients' request for such drugs. Such disorders may need to be
      treated promptly with psychotherapy and/or appropriate psychopharmacotherapy, and
      the choice of the treatment requires an accurate differential diagnostic
      approach.

PMID- 18081755
TI  - Deliberate self-harm by under-15-year-olds: characteristics, trends and outcome.
AB  - BACKGROUND: Relatively little information is available about the characteristics
      and long-term outcome of children and adolescents aged under 15 years who present
      to general hospitals because of deliberate self-harm (DSH). METHOD: Information
      was collected on 710 consecutive under-15-year-olds presenting to a general
      hospital in central England with DSH over a 26-year period (1978-2003). Outcome
      in terms of death was investigated from national statistics in 464 cases
      presenting during the first 20 years of the study. RESULTS: Most individuals were
      aged 12-14 years. In this age group the female:male ratio was 6.5:1. Nearly all
      (680/710, 95.8%) had taken overdoses, over half of these episodes involving
      paracetamol (acetaminophen). Few had a history of prior (7.7%) or current
      psychiatric treatment (7.7%), although a quarter (150/559, 26.8%) had a history
      of previous DSH. Suicidal intent was usually low. The most frequent problems were
      difficulties in relationships with family members (77.3%) and with friends
      (38.9%), and school/study problems (37.9%). The long-term risk of suicide was
      low, 1.1% (N = 5) having died by probable suicide after a mean follow-up period
      of 11 years 2 months. CONCLUSIONS: DSH in children and young adolescents is
      usually related to life problems, is generally of low suicidal intent, and is
      associated with a relatively low long-term risk of suicide.

PMID- 18081756
TI  - Improving early language and literacy skills: differential effects of an oral
      language versus a phonology with reading intervention.
AB  - BACKGROUND: This study compares the efficacy of two school-based intervention
      programmes (Phonology with Reading (P + R) and Oral Language (OL)) for children
      with poor oral language at school entry. METHODS: Following screening of 960
      children, 152 children (mean age 4;09) were selected from 19 schools on the basis
      of poor vocabulary and verbal reasoning skills and randomly allocated to either
      the P + R programme or the OL programme. Both groups of children received 20
      weeks of daily intervention alternating between small group and individual
      sessions, delivered by trained teaching assistants. Children in the P + R group
      received training in letter-sound knowledge, phonological awareness and book
      level reading skills. Children in the OL group received instruction in
      vocabulary, comprehension, inference generation and narrative skills. The
      children's progress was monitored at four time points: pre-, mid- and post
      intervention, and after a 5-month delay, using measures of literacy, language and
      phonological awareness. RESULTS: The data are clustered (children within schools)
      and robust confidence intervals are reported. At the end of the 20-week
      intervention programme, children in the P + R group showed an advantage over the
      OL group on literacy and phonological measures, while children in the OL group
      showed an advantage over the P + R group on measures of vocabulary and
      grammatical skills. These gains were maintained over a 5-month period.
      CONCLUSIONS: Intervention programmes designed to develop oral language skills can
      be delivered successfully by trained teaching assistants to children at school
      entry. Training using P + R fostered decoding ability whereas the OL programme
      improved vocabulary and grammatical skills that are foundations for reading
      comprehension. However, at the end of the intervention, more than 50% of at-risk
      children remain in need of literacy support.

PMID- 18081757
TI  - Verbal ability and delinquency: testing the moderating role of psychopathic
      traits.
AB  - BACKGROUND: Impaired verbal abilities are one of the most consistent risk factors
      for serious antisocial and delinquent behavior. However, individuals with
      psychopathic traits often show serious antisocial behavior, despite showing no
      impairment in their verbal abilities. Thus, the aim of the current study was to
      examine whether psychopathy moderates the relationship between verbal abilities
      and delinquent behavior in a sample of detained youth. METHODS: The sample
      included 100 detained adolescent boys who were assessed on self-reported
      delinquent acts and psychopathic traits, as well as their age at first offense
      based on official records. Participants also completed a competitive computer
      task involving two levels of provocation, during which skin conductance was
      measured. A standard measure of receptive vocabulary was individually
      administered. RESULTS: As predicted, there was a significant interaction between
      callous-unemotional (CU) traits (a critical dimension of psychopathy) and verbal
      ability when predicting violent delinquency. Individuals who were high on CU
      traits with higher scores on the measure of verbal abilities reported the
      greatest violent delinquency. These individuals also showed the lowest level of
      skin conductance reactivity during the provocation task. CONCLUSIONS: The results
      suggest CU traits are an important moderator of the relation between verbal
      abilities and violent delinquency.

PMID- 18081758
TI  - Emotions that afflict the heart: influence of the autonomic nervous system on
      temporal dispersion of myocardial repolarization.

PMID- 18081759
TI  - Anomalous insertion of the right superior pulmonary vein into the left pulmonary
      vein antrum: a previously unreported anomaly affecting ablation for atrial
      fibrillation.

PMID- 18081760
TI  - Ultra rapid local activity in adenosine-induced atrial fibrillation.

PMID- 18081761
TI  - Effect of ischemia on implantable defibrillator intracardiac shock electrograms.
AB  - INTRODUCTION: Few attempts have been made to extract information from the
      ventricular electrogram (EGM) recorded by implantable cardioverter defibrillators
      (ICD) aside from the discrimination of supraventricular tachycardia and
      ventricular tachycardia. The current study aims to examine the effect of ischemia
      in the major coronary artery distributions on the shock EGM from ICDs. METHODS:
      Domestic crossbred pigs (n = 10, 20-40 kg) were implanted with a dual-coil right
      ventricular defibrillation system. Through the femoral approach, percutaneous
      balloon occlusion of the major coronary arteries was performed. The left anterior
      descending (LAD), left circumflex (LCx), and right coronary (RCA) arteries were
      occluded in random order for 3-5 minutes with 30-minute periods of reperfusion in
      between and the shock EGMs were recorded and analyzed. RESULTS: During peak
      ischemia, R wave amplitude increased by a mean of 204.3% (P = 0.003), increased
      by a mean of 73.8% (P = 0.0009), and decreased by a mean of 28.0% (P = 0.109) in
      the LAD, LCx, and RCA territories, respectively. During peak ischemia ST segments
      elevated by a mean of 105.3% (P = 0.041), elevated by a mean of 114.9% (P =
      0.064), and decreased by a mean of 584.5% (P = 0.006) in the LAD, LCx, and RCA
      territories, respectively. CONCLUSIONS: Ischemia affects ICD shock EGMs in a
      manner that appears to vary depending on the culprit vessel. Our data demonstrate
      the feasibility of ischemia detection from ICD shock EGMs.

PMID- 18081762
TI  - Brugada syndrome in pure black Africans.
AB  - AIMS: Although all races are concerned with the Brugada syndrome, no case has
      ever been reported among black Africans. We describe five different cases in this
      specific group of populations. METHODS AND RESULTS: In all patients, Brugada
      syndrome was identified after detailed noninvasive and invasive evaluations. Sex
      ratio was four males for one female. Convulsive syncope was noticed in 1 patient
      with a family history of sudden death. Diagnostic coved-type pattern was observed
      spontaneously in the normal position of right precordial leads in 3 patients and
      in a higher position of leads in 3 patients. Sixty percent had first-degree
      atrioventricular block. An ajmaline test was performed in 4 patients and was
      positive either in normal position of leads or in superior position in all of
      them. Sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) was
      inducible during programmed ventricular stimulation in 3 patients. Right
      ventricular cineangiography found localized apical hypokinesia with preserved
      systolic function in 1 patient. Automatic cardioverter defibrillator was
      implanted in 2 patients. SCN5A was not found in any of the patients. CONCLUSION:
      These observations demonstrate that Brugada syndrome is also present in black
      African populations, and increasingly reported cases of apparent sudden death in
      the sub-Saharan part of the world need to rule out cardiac electrical disturbance
      such as Brugada syndrome.

PMID- 18081763
TI  - A rewarming maneuver demonstrates the contribution of blood flow to electrode
      cooling during internally irrigated RF ablation.
AB  - INTRODUCTION: Titration of radiofrequency (RF) ablation energy to avoid steam
      pops while maximizing lesion size is difficult because of disparities between
      electrode and tissue temperature. We hypothesized that the variable contribution
      of local blood flow to electrode cooling contributes to electrode-tissue
      temperature disparity, even with an irrigated RF catheter. METHODS AND RESULTS:
      Forty RF lesions were made in the atria of live swine with an internally
      irrigated cooled RF catheter. Prior to RF delivery, the catheter tip was cooled
      and then allowed to rewarm to body temperature by stopping irrigant flow. The
      rewarming time (RT) was noted. The catheter was again cooled and RF energy
      delivered, with power titrated to achieve electrode temperature of 40 degrees C,
      which was previously defined as the approximate upper limit of safety. Lesion
      formation and steam pops were observed with intracardiac echocardiography. The RT
      ranged from 10 to 47 seconds. Nine steam pops were seen. The mean RT for lesions
      with pops was faster than those without (20 vs. 33 seconds, P = 0.003). The 20
      lesions with faster RT required more power to achieve target temperature than the
      20 lesions with slower RT (P = 0.01). Eight of nine steam pops occurred in the
      group with faster RT. CONCLUSIONS: RT quantifies convective heating by blood
      prior to RF. Faster RT predicts greater cooling by blood during irrigated RF, a
      greater power requirement to reach target electrode temperature, and a higher
      risk of steam pops during fixed-temperature ablation. RT therefore can
      demonstrate the variation in blood cooling with each lesion and can be used to
      tailor energy delivery to maximize efficacy and safety.

PMID- 18081764
TI  - Sympathoexcitation increases the QT/RR slope in healthy men: differential effects
      of hypoxia, dobutamine, and phenylephrine.
AB  - INTRODUCTION: Dynamic ventricular repolarization assessed by QT/RR slopes studies
      the effects of modifications in cardiac repolarization independently of
      variations in RR interval (RR). The effects of changes in sympathetic and vagal
      activity on the QT/RR slope are controversial. We tested the hypothesis that
      sympathoexcitation is an important determinant of the QT/RR slope. METHODS AND
      RESULTS: We compared the effects of a reflex sympathetic activation in response
      to hypoxia, to the direct effects of the infusion of the beta-adrenergic agent
      dobutamine, on the QTa (apex) and QTe (end)/RR slopes. Dobutamine was titrated to
      obtain similar increases in cardiac output than with hypoxia. Cardiac vagal
      activity was estimated by rMSSD and pNN50. In a second group of healthy subjects,
      we assessed the effect of a reflex cardiac vagal activation in response to
      phenylephrine infusion on the same variables. We observed a similar increase in
      QTa and QTe slopes during hypoxia and dobutamine (both P < 0.017 vs. normoxia),
      despite divergent changes in cardiac vagal activity, as rMSSD and pNN50 decreased
      with hypoxia compared to normoxia (P < 0.001) but increased during dobutamine
      infusion compared to hypoxia (P < 0.017). In contrast, these slopes did not
      change during the rises in rMSSD and pNN50 elicited by phenylephrine (P > 0.7).
      CONCLUSION: Beta-adrenergic stimulation induces comparable increases in the QT/RR
      slopes than hypoxia, but in the presence of a larger cardiac vagal activity.
      Vagal cardiac activation by phenylephrine does not change the QT slopes. This
      reveals that the sympathetic system is an important determinant of QT/RR
      dynamicity in healthy men.

PMID- 18081765
TI  - Mental health in migrant children.
AB  - Many factors have been identified to explain differences in mental health
      problems between migrant and native children: the process of migration, the
      ethnic minority position of migrants, their specific cultural background and the
      selection of migrants. In this paper, the international literature regarding
      mental health of migrant children is reviewed using strict selection criteria. An
      extensive search was carried out to locate journal articles on the subject of
      mental health in migrant youth published since the 1990s. Only 20 studies met all
      inclusion criteria. Besides the conclusion that the studies did not unequivocally
      find an increased risk of mental health problems in migrant children, it proved
      to be very difficult to draw any sound conclusions with respect to these
      children's risk of mental health problems, since the impact of migration on
      children's mental health varied with the informants used and the characteristics
      of the migrant group and of the host country. The lack of univocal definitions of
      key terms further complicated generalised conclusions in this research field. As
      such, this research field is in urgent need of more research using standardised
      research designs, methodology and definitions. A proposition for this research
      design is made.

PMID- 18081766
TI  - Research review: dopamine transfer deficit: a neurobiological theory of altered
      reinforcement mechanisms in ADHD.
AB  - This review considers the hypothesis that changes in dopamine signalling might
      account for altered sensitivity to positive reinforcement in children with ADHD.
      The existing evidence regarding dopamine cell activity in relation to positive
      reinforcement is reviewed. We focus on the anticipatory firing of dopamine cells
      brought about by a transfer of dopamine cell responses to cues that precede
      reinforcers. It is proposed that in children with ADHD there is diminished
      anticipatory dopamine cell firing, which we call the dopamine transfer deficit
      (DTD). The DTD theory leads to specific and testable predictions for human and
      animal research. The extent to which DTD explains symptoms of ADHD and effects of
      pharmacological interventions is discussed. We conclude by considering the neural
      changes underlying the etiology of DTD.

PMID- 18081767
TI  - Psychological problems in children with cerebral palsy: a cross-sectional
      European study.
AB  - OBJECTIVES: To describe psychological symptoms in 8-12-year-old children with
      cerebral palsy; to investigate predictors of these symptoms and their impact on
      the child and family. DESIGN: A cross-sectional multi-centre survey.
      PARTICIPANTS: Eight hundred and eighteen children with cerebral palsy, aged 8-12
      years, identified from population-based registers of cerebral palsy in eight
      European regions and from multiple sources in one further region. MAIN OUTCOME
      MEASURES: The Strengths and Difficulties Questionnaire (SDQ)(P4-16) and the Total
      Difficulties Score (TDS) dichotomised into normal/borderline (TDS < or = 16)
      versus abnormal (TDS > 16). STATISTICAL ANALYSIS: Multilevel, multivariable
      logistic regression to relate the presence of psychological symptoms to child and
      family characteristics. RESULTS: About a quarter of the children had TDS > 16
      indicating significant psychological symptoms, most commonly in the domain Peer
      Problems. Better gross motor function, poorer intellect, more pain, having a
      disabled or ill sibling and living in a town were independently associated with
      TDS > 16. The risk of TDS > 16 was odds ratio (OR) = .2 (95% CI: .1 to .3)
      comparing children with the most and least severe functional limitations; OR =
      3.2 (95%CI: 2.1 to 4.8) comparing children with IQ < 70 and others; OR = 2.7 (95%
      CI: 1.5 to 4.6) comparing children in severe pain and others; OR = 2.7 (95%
      CI:1.6 to 4.6) comparing children with another disabled sibling or OR = 1.8
      (95%CI: 1.2 to 2.8) no siblings and others; OR = 1.8 (95% CI: 1.1 to 2.8)
      comparing children resident in a town and others. Among parents who reported
      their child to have psychological problems, 95% said they had lasted over a year,
      37% said they distressed their child and 42% said they burdened the family at
      least 'quite a lot'. CONCLUSIONS: A significant proportion of children with
      cerebral palsy have psychological symptoms or social impairment sufficiently
      severe to warrant referral to specialist services. Care must be taken in the
      assessment and management of children with cerebral palsy to ensure psychological
      problems are not overlooked and potentially preventable risk factors like pain
      are treated effectively. The validity of the SDQ for children with severe
      disability warrants further assessment.

PMID- 18081768
TI  - A single Mahaim fiber causing both antidromic and orthodromic reciprocating
      tachycardia.
AB  - We describe the case of a 56-year-old woman referred for electrophysiological
      (EP) testing for medically refractory supraventricular arrhythmias. During the EP
      study, the patient was found to have a right free wall atriofasicular (Mahaim
      type) accessory pathway and an inducible left bundle morphology preexcited
      tachycardia secondary to antidromic reciprocating tachycardia. The patient also
      had an inducible narrow complex orthodromic reciprocating tachycardia (ORT).
      Mapping revealed that the earliest site of retrograde atrial activation during
      ORT was along the lateral tricuspid annulus. This was the same location where the
      atriofasicular accessory pathway potential was recorded during sinus rhythm.
      Radiofrequency ablation at this site eliminated inducibility of both tachycardias
      and any evidence of antegrade or retrograde accessory pathway conduction. This
      report describes the case of a very rare right free wall Mahaim type fiber with
      both antegrade and retrograde conduction capabilities responsible for both
      antidromic and ORT.

PMID- 18081769
TI  - Temporal stability of the location of the esophagus in patients undergoing a
      repeat left atrial ablation procedure for atrial fibrillation or flutter.
AB  - BACKGROUND: The esophagus may be mobile during a left atrial (LA) ablation
      procedure for atrial fibrillation (AF). OBJECTIVE: The goal of the study was to
      determine whether the location of the esophagus is stable in patients undergoing
      a repeat LA ablation procedure. METHODS: Forty-two patients underwent repeat LA
      ablation a mean of 7 +/- 2 months after the initial procedure. Cinefluoroscopic
      images of the esophagus during a barium swallow were recorded and the course of
      the esophagus was tagged on the 3D map. The position of the esophagus at the
      index and repeat procedure were compared. RESULTS: At the index procedure, the
      esophagus was located near the left pulmonary veins (PVs) in 20 (48%), right PVs
      in 13 (31%), and at the mid LA in 9 (21%) patients. During the repeat procedure,
      the esophagus was found to be near the left PVs in 22 (52%), right PVs in 11
      (26%), and at the mid LA in 9 patients (21%). In 35 of the 42 patients (83%),
      there was no change in the esophageal location, and in the remaining seven
      patients (17%), its position had shifted by > or =1 cm (range 1.0-4.0 cm).
      CONCLUSIONS: In more than 80% of patients presenting for a repeat LA ablation
      procedure, the esophagus is in the same position relative to the PVs as during
      the initial procedure. Therefore, if radiofrequency ablation at a particular
      location was limited by the position of the esophagus, safe ablation at that site
      is unlikely to be feasible during a repeat procedure.

PMID- 18081770
TI  - Differences in 12-lead electrocardiogram between symptomatic and asymptomatic
      Brugada syndrome patients.
AB  - INTRODUCTION: Brugada syndrome (BrS) is an inherited disorder that predisposes
      some subjects to sudden cardiac death (SCD). It is not well established which BrS
      patients are at risk of severe arrhythmias. Our aim was to study whether standard
      12-lead electrocardiogram (ECG) would give useful information for this purpose.
      METHODS: This study included 200 BrS probands (142 male, 62%; mean age 42 +/- 16
      years). Symptoms related to BrS were defined as syncope, documented ventricular
      tachyarrhythmia, or SCD. We determined PR, QRS, QTc, T(peak), and T(end) interval
      from leads II and V(2) and QRS from lead V(5), R'/S ratio from lead aVR (aVR
      sign), QRS axis, and J-point elevation amplitude from right precordial leads from
      the baseline ECGs. RESULTS: Sixty-six subjects (33%) had experienced symptoms
      related to BrS. The only significant difference between the symptomatic and
      asymptomatic BrS subjects was the QRS duration measured from lead II or lead
      V(2), for example, the mean QRS in V(2) was 115 +/- 26 ms in symptomatic versus
      104 +/- 19 ms in asymptomatic patients (P < 0.001). The optimized cut-off point
      of V(2) QRS > or =120 ms gave an odds ratio (OR) of 2.5 (95% CI: 1.4-4.6, P =
      0.003) for being symptomatic. In a multivariate analysis adjusted with gender,
      age, and SCN5A mutation, the OR was 2.6 (95% CI: 1.4-4.8, P = 0.004). CONCLUSION:
      Prolonged QRS duration, measured from standard 12-lead ECG, is associated with
      symptoms and could serve as a simple noninvasive risk marker of vulnerability to
      life-threatening ventricular arrhythmias in BrS.

PMID- 18081771
TI  - GOLDART--Gold Alloy Versus Platinum-Iridium Electrode for Ablation of AVNRT.
AB  - INTRODUCTION: Radiofrequency (RF) catheter ablation targeting the slow pathway is
      currently the most effective treatment for patients with atrioventricular nodal
      reciprocating tachycardia (AVNRT). Gold exhibits a more than four times greater
      thermal conductivity than platinum, and the creation of deeper lesions was
      demonstrated in ex vivo animal experiments. The current clinical trial was
      initiated to compare gold catheters with standard platinum-iridium (Pt-Ir)
      material and to analyze differences in the increase of power or temperature as a
      function of time during RF ablation. METHODS: A prospective, randomized
      multicenter study design was used to compare RF deliveries at the slow pathway
      with standard Pt-Ir tip catheters (128 patients), as well as gold alloy tip
      electrodes (124 patients) during AVNRT ablation. RESULTS: Although there was a
      trend towards higher power delivery in the gold group (4.96 vs. 4.28 W/s), this
      trend was not statistically significant. Likewise, cumulative duration of all RF
      ablations, total procedure time, and power delivered at other time points were
      not significantly different between the groups. Also, the occurrence of AV-block
      and sensations of pain were similar in both treatment groups. However, charring
      on the catheter tip after the intervention was observed eightfold more frequently
      in the Pt-Ir group. CONCLUSION: In conclusion, power delivery cannot be
      significantly increased by RF ablation of AVNRT with gold electrodes. But the
      electrode material seems to be safe and well-tolerated and specifically did not
      increase the risk of AV-block. The significant reduction of coagulum formation on
      gold tips suggests a possible advantage of this material beyond its better
      conduction properties.

PMID- 18081772
TI  - Time and temperature profile of catheter cryoablation of right septal and free
      wall accessory pathways in children.
AB  - INTRODUCTION: The overall acute success with cryoablation for accessory pathways
      (APs) has been reported to be lower than with radiofrequency ablation. Generally,
      prior cryomapping (limited to -30 degrees C) has been used to test for loss of AP
      conduction and absence of atrioventricular (AV) node impairment. However, the
      temperature at which loss of AP conduction occurs may be variable. The purpose of
      this study was to evaluate the time and temperature profile at which loss of AP
      conduction occurs. METHODS AND RESULTS: A retrospective study evaluated 25
      patients (mean age 13.3 +/- 3.6 years) who underwent cryoablation for right-sided
      APs (22 manifest/3 concealed). Direct cryoablation (-80 degrees C) without
      cryomapping was performed using a "time to success" strategy. If AP conduction
      was successfully interrupted within 25 seconds of the onset of cryoablation, the
      lesion was continued for 240 seconds; otherwise it was terminated and further
      mapping was performed. Cryoablation was successful in 24/25 (96%) patients.
      Temperature at loss of AP conduction was -66.2 +/--16.7 degrees C (range +32 to 
      84 degrees C) with conduction block at temperatures lower than -30 degrees C for
      all but 3 APs. Critical time to success (interval from cryoadherence to loss of
      AP conduction) was significantly shorter for permanently successful cryolesions,
      compared with transiently successful lesions (6.3 +/- 4.1 vs. 11.2 +/- 2.2 sec; P
      < 0.001). There were no major complications. CONCLUSIONS: Cryothermal energy
      required for successful ablation may be variable and restricting test
      applications to -30 degrees may limit its efficacy. A "time to success" strategy
      may improve outcome of cryoablation for right-sided APs in children without
      compromising safety.

PMID- 18081773
TI  - Complications associated with generator replacement in response to device
      advisories.
AB  - INTRODUCTION: Device recalls create problems for patients and physicians, for the
      risks associated with replacement may be greater than the device failure rate. In
      2005, Medtronic, Guidant, and St. Jude had implantable cardioverter defibrillator
      (ICD) recalls on several of their devices. There were no national standards to
      guide physicians on the management of such patients. We report the reasons for
      and outcomes of ICD and pacemaker generator changes from our practice resulting
      from these advisories. METHODS AND RESULTS: After an advisory was issued, the
      patients with an affected device were contacted, evaluated in the office by one
      of the electrophysiologists in our group, and a management plan was determined.
      Two hundred and twenty-two of 1,039 (Medtronic 273, Guidant 766) (21.4%) patients
      with advisory devices underwent device replacement. Nine minor complications
      occurred: hematoma managed conservatively (n = 6); local discomfort (n = 1); and
      incisional infections treated successfully with oral antibiotics (n = 2). Major
      complications occurred in nine patients (4.1%). Four atrial leads were damaged,
      two of which were repaired, one during the same procedure and the other at a
      later date. One patient required a reoperation to tighten a loose ventricular
      lead set screw. Hematoma requiring evacuation occurred in one patient, and pocket
      revision was necessary in two patients secondary to severe discomfort due to the
      positioning of the device in the pocket. One patient had a cerebrovascular
      accident preoperatively. There were no perioperative deaths or infections
      requiring system removal. CONCLUSION: Even with experienced operators
      complications can occur when replacing generators for a device recall. Careful
      risk assessment for each individual patient should be performed and efforts made
      to minimize generator changes.

PMID- 18081774
TI  - The adhesion of putative probiotic lactobacilli to cultured epithelial cells and
      porcine intestinal mucus.
AB  - AIMS: To investigate the adhesion of lactobacilli and their subsequent
      competitive exclusion ability against pathogens. METHODS AND RESULTS: Four
      species of putative probiotic lactobacilli were studied for their adhesion
      abilities. First, the adhesion to Caco-2 cells was examined by light and electron
      microscopy. The four species were then labelled by [methyl-(3)H] thymidine and
      their adhesion to porcine intestinal mucus was determined by radioactivity. The
      tested lactobacilli showed best adhesion on ileal mucus compared with duodenal
      and jejunal mucus. Oxidative compound pre-treatment (NaIO(3) and NaIO(4))
      dramatically decreased the adhesion of the lactobacilli to mucus. Pre-treating
      mucus with proteolytic enzymes (proteinase K and trypsin) resulted in the
      increase of adhesion in Lactobacillus serotype Reuteri I2021, but the results in
      the other species were variable. Lactobacillus serotype Fermentum I5007 showed
      greatest adhesion potential and exerted the best competitive exclusion against
      Salmonella and Escherichia. CONCLUSIONS: Adhesion ability in lactobacilli is
      species-specific. Lactobacilli with higher adhesion index have better competitive
      exclusion ability. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that
      there is a positive correlation between adhesion and competitive exclusion
      ability of lactobacilli. Additionally, the in vitro adhesion assay is a feasible
      way to screen unknown lactobacilli, potentially for future industrial
      applications.

PMID- 18081775
TI  - Discrimination of gamma-irradiated and nonirradiated Vibrio vulnificus by using
      real-time polymerase chain reaction.
AB  - AIMS: To develop a PCR strategy for Vibrio vulnificus in irradiated foods.
      METHODS AND RESULTS: Real-time PCR was used to discriminate between DNA from
      gamma-irradiated and nonirradiated cells. gamma-Irradiation at 1.08 KGy and above
      of cell suspensions containing 1 x 10(6) CFU ml(-1) resulted in 0 CFU ml(-1).
      Real-time PCR was able to detect 86.6% destruction by 1.08 KGy, while ethidium
      bromide monoazide (EMA) real-time PCR was able to detect 93.2% destruction at
      this dose. With 3.0 and 5.0 KGy, EMA real-time PCR was able to detect 99.3% and
      100% destruction, respectively. CONCLUSIONS: The inability to detect via PCR
      extensively degraded DNA resulting from gamma-irradiation can be taken as
      evidence of cell death. The increased ability of EMA to further reduce the
      detectable number of target sequences via PCR, with DNA from cells exposed to
      increased doses of gamma-irradiation, can be considered to reflect the
      accompanying increase in membrane damage which allows EMA to penetrate the cells.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study that has made use
      of the PCR to discriminate between gamma-irradiated and nonirradiated bacterial
      cells and has led to insights regarding the ability of the PCR to discriminate
      between nonirradiated and gamma-irradiation destroyed cells.

PMID- 18081776
TI  - Influence of epigallocatechin gallate and phenolic compounds from green tea on
      the growth of Oenococcus oeni.
AB  - AIMS: To investigate the effect of phenolic compounds on the growth of Oenococcus
      oeni. METHODS AND RESULTS: Oenococci are usually grown in media often
      supplemented with complex additives such as tomato juice. In order to improve our
      knowledge about the growth requirements of oenococci, we added several juices and
      leaf extracts such as green tea to the culture media and screened them for growth
      stimulating substances to substitute complex supplements such as juices by more
      defined components. We found that also green tea could cause a growth stimulation
      of Oenococcus oeni strain B2. CONCLUSIONS: Further experiments showed that the
      stimulating effect was as a result of the phenolic compounds of green tea,
      especially epigallocatechin gallate (EGCG). On the other hand, EGCG could also
      inhibit the growth of O. oeni strain B2 just depending on its concentration.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Individual catechins should have a minor
      influence on the growth of oenococci during wine making as their concentration in
      grapes is <30 mg kg(-1) grape. Whether there is a synergistic effect of the
      different catechins in wine has to be investigated.

PMID- 18081777
TI  - Assessment of real-time RT-PCR for quantification of Lactobacillus plantarum gene
      expression during stationary phase and nutrient starvation.
AB  - AIMS: In this study, we evaluated the impact of different real-time reverse
      transcription PCR (RT-PCR) data normalization methods on the interpretation of
      stationary-phase and nutrient-starved Lactobacillus plantarum WCFS1 gene
      expression levels. METHODS AND RESULTS: Lactobacillus plantarum WCFS1 culture
      characteristics and housekeeping gene transcripts were measured during stationary
      phase in standard growth medium and during extreme nutrient starvation. These
      conditions differentially affected L. plantarum viability and RNA/DNA ratios.
      Real-time RT-PCR gene expression data were normalized according to three
      different methods: (i) total RNA amounts added to the reactions; (ii) the
      comparative 2(-Delta Delta Ct) method using recA as a reference; and (iii) the
      geNorm approach based on the average expression values of several housekeeping
      genes. Each of these methods revealed differences in the abundance of
      housekeeping gene transcripts between L. plantarum in the exponential phase of
      growth and in stationary phase or undergoing nutrient starvation. CONCLUSIONS:
      Real-time RT-PCR data analysis with a normalization factor comprised of several
      of the most stably expressed housekeeping genes best accounted for the expected
      activity levels of the cells contained in the different cultures. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The relative normalization of real-time RT-PCR data
      using multiple housekeeping reference genes should be useful for the
      quantification of bacterial gene expression levels in nonoptimal growth
      conditions in situ.

PMID- 18081778
TI  - Habitat utilization by coral reef fish: implications for specialists vs.
      generalists in a changing environment.
AB  - 1. The impact of environmental disturbance and habitat loss on associated species
      is expected to be dependent on a species' level of specialization. We examined
      habitat use and specialization of coral reef fish from the diverse and
      ecologically important family Pomacentridae, and determined which species are
      susceptible to declines in coral cover due to disturbance induced by crown-of
      thorns seastar (COTS, Acanthaster planci L.). 2. A high proportion of pomacentrid
      species live in association with live coral as adults (40%) or juveniles (53%).
      Adults of many species had strong affiliations with branching corals, while
      juveniles favoured plating growth forms, reflecting the sizes of refuge provided
      by coral types. 3. Juveniles of species that associated with coral had narrower
      niche breadths than adult conspecifics, due to associations with specific coral
      types. The especially high coral association and narrower niche breadth of
      juveniles suggest that the presence of live coral is crucial for many species
      during early life history, and that disturbance-induced coral loss may have
      serious flow-on effects on adult abundance. 4. Microhabitat availability was a
      poor predictor of fish species abundance. Significant correlations between
      coverage of coral types and abundance of five adults and two juvenile species
      were detected; however, these relationships explained <35% and <10% of the
      variation in abundance of adult and juvenile species, respectively. 5. Niche
      breadth explained 74% of the variation in species' mean response to coral decline
      and it is clear that disturbance has a greater impact on resource specialists,
      suggesting that increasing frequency and intensity of coral loss will cause reef
      fish communities to become dominated by habitat generalists at the expense of
      coral-dwelling specialists.

PMID- 18081779
TI  - Density dependence hypotheses and the distribution of fecundity.
AB  - 1. Beja & Palma (2008, Journal of Animal Ecology, 77, doi: 10.1111/j.1365
      2656.2007.01312.x) attempt to provide a critical analysis of the effectiveness
      and limitations of a previously published method (Ferrer et al. 2006, Journal of
      Animal Ecology, 75, 111-117.) to discriminate between Habitat Heterogeneity
      Hypothesis and the Individual Adjustment Hypothesis using real data from a
      Bonelli's eagle Hieraaetus fasciatus population. 2. They conclude that
      significant and strong correlations between mean and CV or skewness are expected
      under a biologically plausible assumption about brood size distribution, and that
      the two hypotheses cannot therefore be distinguished. 3. A major concern we have
      with their paper centres on this biologically plausible brood-size distribution.
      They used the same quasi-Poisson distribution of brood sizes (typical for a
      saturate population under Habitat Heterogeneity Hypothesis) for both families of
      simulations. So, is not surprising that both groups gave similar results. 4. They
      argued that this approach was 'empirical', free of theoretical assumptions. But
      in testing between hypotheses, what we are looking for is precisely the
      differences among theoretical brood-size distributions predicted under the two
      hypotheses. 5. Summarizing, with the same mean fecundity at high densities, both
      hypotheses must have different brood-size distributions. So the use of a single
      left-skewed distribution, typical of a real saturated population (most likely
      under Habitat Heterogeneity Hypothesis) in attempts to distinguish between the
      two hypotheses by re-sampling several times on the same left-skewed distribution,
      as done by Beja & Palma, is clearly inappropriate.

PMID- 18081780
TI  - The evolution of prey body size reaction norms in diverse communities.
AB  - 1. Heterogeneous predation risks can select for predator-specific plastic
      defences in prey populations. However, diverse predation threats can generate
      diffuse selection, which, in turn, can lead to the evolution of more generalized
      reaction norms. Unreliable predator cues also can select for more generalized
      plasticity in prey. 2. Here, I evaluated the extent to which variation in risk
      from a focal predator vs. variation in risk from predator diversity and
      composition were associated with variation in body mass reaction norms in 18 prey
      populations. Toward this end, I assayed the body mass reaction norms in a common
      garden experiment for spotted salamander larvae Ambystoma maculatum in response
      to marbled salamander predators Ambystoma opacum, local predator richness and the
      densities of two auxiliary predator species. 3. When raised under controlled
      conditions, prey larvae generally were smaller when exposed to A. opacum
      kairomones. Among populations, the mean and slope of body mass variation was
      unrelated to A. opacum's local density. 4. Predator richness and several key
      environmental factors were not associated with reaction norm variation. Instead,
      the density of an auxiliary newt predator species was correlated with reduced
      mass reaction norm slopes. Results suggest that diffuse selection from auxiliary
      predators can modify the evolution of life-history plasticity.

PMID- 18081781
TI  - Biotic disturbance and benthic community dynamics in salmon-bearing streams.
AB  - 1. Organisms can impact ecosystems via multiple pathways, often with positive and
      negative impacts on inhabitants. Understanding the context dependency of these
      types of impacts remains challenging. For example, organisms may perform
      different functions at different densities. 2. Anadromous salmon accumulate > 99%
      of their lifetime growth in marine ecosystems, and then return to spawn, often at
      high densities, in relatively confined freshwaters. While previous research has
      focused on how salmon nutrients can fertilize benthic communities, we examined
      how an ecosystem engineer, sockeye salmon Oncorhynchus nerka, influences seasonal
      dynamics of stream benthic communities through their nest-digging activities in
      south-western Alaska, USA. Benthic invertebrate and algal abundance were
      quantified every 7-14 days during the open water seasons of 10 streams in riffle
      and run habitats across multiple years, leading to 25 different stream-year
      combinations that spanned a large gradient of salmon density. 3. In streams with
      few or no salmon, benthic algal and insect biomass were fairly constant
      throughout the season. However, in streams with more than 0.1 salmon m(-2), algal
      and insect biomass decreased by an average of 75-85% during salmon spawning.
      Algal biomass recovered quickly following salmon disturbance, occasionally
      reaching pre-salmon biomass. In contrast, in streams with more than 0.1 salmon m(
      2), aquatic insect populations did not recover to pre-salmon levels within the
      same season. We observed no positive impacts of salmon on algae or insects via
      fertilization from carcass nutrients. 4. Salmon, when their populations exceed
      thresholds in spawning density, are an important component of stream disturbance
      regimes and influence seasonal dynamics of benthic communities. Human activities
      that drive salmon densities below threshold densities, as has likely happened in
      many streams, will lead to altered seasonal dynamics of stream communities. Human
      activities that alter animal populations that are sources of biogenic disturbance
      can result in shifts in community dynamics.

PMID- 18081782
TI  - Radiotherapy and wound healing.
AB  - This review article discusses basic radiation physics and effects of radiation on
      wounds. It examines various postulated hypothesis on the role of circulatory
      decrease and radiation-induced direct cellular damage. The new concept related to
      the radiation pathogenesis proposes that there is a cascade of cytokines
      initiated immediately after the radiation. Sustained activation of myofibroblasts
      in the wound accounts for its chronicity. Recent advances highlight that
      transforming growth factor beta1 is the master switch in pathogenesis of
      radiation fibrosis. This articles overviews its role and summarises the available
      evidences related to radiation damage. The goal of this article was to provide
      its modern understanding, as future research will concentrate on antagonising the
      effects of cytokines to promote wound healing.

PMID- 18081783
TI  - Neonatal necrotising fasciitis--Varanasi experience.
AB  - Neonatal necrotising fasciitis (NNF) is a rare and fatal disorder. Successful
      outcome depends on timely intervention. This paper presents single-centre
      experience of presentation, management and outcome of the condition. Fifteen
      patients of NNF were managed during the study period of 5 years. Parameters
      studied were age, sex, site of involvement and treatment. Treatment included
      intravenous (i.v.) antibiotics and conservative surgery. Age of presentation was
      10-28 days. Male to female ratio was 2:1. Neck and scalp were the commonest site
      (53.3%). Culture reports were unimicrobial in 66% with predominance of
      Staphylococcus species. Predisposing factors included rural environment (100%),
      malnourishment (60%), boils (40%) and scratch injury (13%). Forty per cent had
      idiopathic NNF. Wound healing was by secondary intention in 46.6% and skin
      grafting in 53.3%. Overall survival was 80%, while the premature had poorer
      outcome. NNF is a serious disorder. Early treatment with i.v. antibiotics and
      supportive measures followed by debridement improves survival.

PMID- 18081784
TI  - When will I see you again? The fate of research findings from international wound
      care conferences*.
AB  - Medical conferences provide a forum for the rapid dissemination of research
      directly to health professionals and academics. However, the published record of
      poster and oral presentations from these meetings is usually limited to
      abstracts. We aimed to assess how many wound studies presented as conference
      abstracts were eventually published in journals and to identify the factors that
      predicted publication. The study was a retrospective review. We identified
      abstracts relating to oral and poster presentation from two large wound
      conferences. Following data extraction from the abstracts, a systematic search
      was conducted to examine if the research was subsequently published as a journal
      article. A time-to-event analysis was conducted to assess predictive associations
      between features of the research reported in the conference abstracts and time to
      full publication. In total, 492 abstracts from two European wound care
      conferences were identified (467 after exclusions). Of the abstracts included,
      60% (279) were for posters and 40% (188) were for oral presentations. Over half
      of the abstracts (53%) reported results from case studies or case series design.
      In total, only 57 (12%) of the abstracts included resulted in a related
      publication. Analysis suggested that those studies reporting positive findings
      were significantly more likely to be published (hazard ratio 1.79, P= 0.001, 95%
      CIs 1.26-2.55). Few studies presented as conference abstracts at these two wounds
      conferences were subsequently published. This may be because of the low
      methodological quality of studies accepted for poster or oral presentation.

PMID- 18081785
TI  - Leg ulceration in Portugal: quality of life.
AB  - This study was undertaken to examine the impact of chronic leg ulceration on
      patients' health-related quality of life in an audit of practice in Lisbon,
      Portugal, and to observe the changes following 12 weeks of treatment. A
      questionnaire was administered at entry into an observational study and following
      12 weeks of treatment. Patients entering the study were asked to complete the
      Nottingham Health Profile (NHP), Euroqol and visual analogue (VA) pain
      questionnaires at entry and after 12 weeks. Principal analysis compared final
      scores with those found at baseline and compared results with Portuguese
      normative data. In total, 98 patients entered the study and completed the initial
      questionnaire, with 68 (69.3%) patients completing the follow-up questionnaire.
      There were significantly (P < 0.001) higher scores for the patients compared with
      normative data for all domains of the NHP (all P < 0.001). Improvements were
      noted for all NHP scores after 12 weeks, although only bodily pain showed a
      significant improvement [mean difference (d) = 10.5, P = 0.003], with significant
      improvement also in Euroqol (d = 0.10, P = 0.027). Energy and social isolation
      improved substantially in the eight (11.8%) patients whose ulcers healed, but did
      not achieve statistical significance, although VA pain score did (d = 4.85, P <
      0.001). Patients suffering from leg ulceration show modest improvements in
      perceived health following 12 weeks of usual care in Portugal. Improvements in
      practice may enhance the magnitude of these improvements.

PMID- 18081786
TI  - Abdominal wall mucocele: a late complication of colostomy closure.
AB  - We present a case of incisional enteric mucocele formation 10 years following
      colostomy closure. The patient was admitted to the hospital with the symptoms of
      an abdominal wall mass lying on previously closed colostomy incision. Clinical
      presentation, diagnostic work up and pathology of the case were discussed. To our
      knowledge, this is the first abdominal wall mucocele after colostomy closure
      reported in the literature.

PMID- 18081788
TI  - Protein expression levels of excision repair cross-complementation group 1 and
      xeroderma pigmentosum D correlate with response to platinum-based chemotherapy in
      the patients with advanced epithelial ovarian cancer.
AB  - This study was undertaken to examine whether there is an association between
      excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum D
      (XPD) protein expression levels and response to platinum-based chemotherapy in
      epithelial ovarian cancer (EOC). The study cohort consisted of 91 consecutive
      patients suffering from stage III or IV disease of primary EOC from 1999 to 2004
      at the Women's Hospital, School of Medicine, Zhejiang University. There were 36
      sensitive cases of serous ovarian cancer, 27 resistant cases of serous ovarian
      cancer, 15 cases of clear cell cancer, and 13 cases with serous ovarian cancer
      receiving neoadjuvant chemotherapy. The ovarian tissue microsections were stained
      by standard immunohistochemical techniques to show ERCC1 and XPD protein
      expression levels. In resistance group of serous ovarian cancer, ERCC1 and XPD
      protein expression levels were significantly higher than those of sensitivity
      group, and after receiving neoadjuvant chemotherapy, they showed 23% and 32%
      higher than before. Meanwhile, their levels of clear cell cancer group were
      significantly higher than serous ovarian cancer group's. Upregulation of ERCC1
      and XPD protein expression was associated with resistance process to platinum
      based chemotherapy in advanced EOC. This study provided evidence that differences
      of nucleotide excision repair-related genes expression may have an effect on the
      observed differences in clinical behavior of EOC.

PMID- 18081789
TI  - Clinical and pathologic prognostic factors in adult granulosa cell tumors of the
      ovary.
AB  - The objective of this study was to determine the clinicopathologic prognostic
      factors in adult granulosa cell tumors of the ovary. A retrospective review of
      the records of patients of granulosa tumors who were treated at our institute
      over a period of 10 years (1995-2005) was done. Clinical, pathologic, and follow
      up data were collected. A total of 34 patients who were treated during this
      period were subjected to analysis. Cox univariate analysis and Wilcoxon's test
      for multivariate analysis were used as part of the SPSS software for examining
      the data. It was found that optimal cytoreduction (P = 0.02), presence of nuclear
      atypia (P < 0.001), and increased mitoses (P = 0.03) were the three factors that
      impacted significantly on survival. Age, stage of the tumor, parity, and size of
      the tumor had no significant effect on survival. Patients who received
      chemotherapy had a better median disease-free survival than those who did not (60
      vs 48 months), but this did not reach statistical significance (P = 0.08).
      Optimal cytoreduction, nuclear atypia, and increased mitoses are the
      statistically significant prognostic factors and may be used for selecting
      patients for adjuvant therapy.

PMID- 18081790
TI  - A qualitative study: beliefs and attitudes of women undergoing abdominal
      hysterectomy in Turkey.
AB  - The study was designed as a descriptive one to reveal the beliefs and attitudes
      of the women undergoing abdominal hysterectomy. It was carried out at the
      university hospital in Erzurum between July 2005 and March 2006. The data were
      collected through semistructured in-depth interviews with 31 women undergoing
      abdominal hysterectomy. The data obtained were evaluated by content analysis.
      These evaluations revealed five themes concerning the beliefs and attitudes of
      the women undergoing abdominal hysterectomy: (1) feminine identity, (2)
      husband/family relationships, (3) sexual life, (4) menopause, and (5) relatives'
      opinions. These findings about cultural beliefs and attitudes of the women
      undergoing hysterectomy will enable health care providers to provide culturally
      sensitive and comprehensive care to women; it is also expected to enable health
      care providers to instruct women to avoid unnecessary delay of hysterectomy.

PMID- 18081791
TI  - Desmoplastic small round cell tumor masquerading as advanced ovarian cancer.
AB  - Desmoplastic small round cell tumor (DSRCT) is a rare abdominal malignancy
      usually diagnosed in young adult males. Most patients have widespread disease at
      presentation, with an organ of origin difficult to ascertain. A 33-year-old
      female presented to her gynecologist with complaints of suprapubic pressure,
      abdominal pain, and increased abdominal girth. She had a large intraabdominal
      tumor on ultrasound, thought to be ovarian cancer. She underwent surgical
      exploration, which confirmed a malignancy, but the exact etiology was uncertain.
      Final pathology was consistent with DSRCT. DSRCT is a rare malignancy that can
      mimic other more commonly seen tumors such as lymphoma and ovarian cancer. When
      encountering an extensive intraabdominal malignancy of uncertain etiology, DSRCT
      should be in the differential diagnosis.

PMID- 18081792
TI  - Low response rate of second-line chemotherapy for recurrent or refractory clear
      cell carcinoma of the ovary: a retrospective Japan Clear Cell Carcinoma Study.
AB  - Clear cell carcinoma (CCC) of the ovary has been recognized to show resistance to
      anticancer agents in the first-line chemotherapy. Our aim was to evaluate the
      effect of second-line chemotherapy in a retrospective study. A total of 75
      patients diagnosed with CCC and treated between 1992 and 2002 in collaborating
      hospitals were reviewed. Criteria for the patients' enrollment were 1) diagnosis
      of pure-type CCC at the initial operation, 2) treatment after one systemic
      postoperative chemotherapy, 3) measurable recurrent or refractory tumor, 4) at
      least two cycles of second-line chemotherapy and assessable for the response, and
      5) adequate clinical information. Regimens of first-line chemotherapy were
      conventional platinum-based therapy in 33 cases, paclitaxel plus platinum in 24
      cases, irinotecan plus platinum in 9 cases, and irinotecan plus mitomycin C in 7
      cases. Treatment-free periods were more than 6 months in 24 cases (group A) and
      less than 6 months in 51 cases (group B). In group A, response was observed in
      two cases (8%): one with conventional platinum therapy and another with
      irinotecan plus platinum. In group B, three cases (6%) responded: two with
      platinum plus etoposide and one case with irinotecan plus platinum. Median
      overall survival was 16 months in group A and 7 months in group B (P = 0.04).
      These findings suggest recurrent or resistant CCC is extremely chemoresistant,
      and there is only small benefit of long treatment-free period in CCC patients.
      Another strategy including molecular-targeting therapy is warranted for the
      treatment of recurrent or refractory CCC.

PMID- 18081793
TI  - Potential benefit of Sunitinib in recurrent and refractory ovarian clear cell
      adenocarcinoma.
AB  - Ovarian clear cell adenocarcinoma (OCCA) is a unique biological subtype of
      epithelial ovarian cancer, with a similar gene profile to renal cell carcinoma
      (RCC). Sunitinib is a vascular endothelial growth factor receptor tyrosine kinase
      inhibitor with proven antitumor activity in RCC and a rational biological option
      for treatment of OCCA. A 60-year-old woman presented with recurrent and
      refractory stage IA OCCA, after 9 years of remission. Sunitinib was initiated as
      fifth-line chemotherapy, associated with cystic degeneration of liver metastasis
      and a short downward trend in her CA125 level. Recurrent and refractory OCCA may
      respond to Sunitinib. Clinical trials are needed to objectively confirm these
      findings, as benefit may be limited in patients with extensively pretreated
      tumors.

PMID- 18081794
TI  - Sentinel node procedure in vulvar squamous cell carcinoma: a histomorphologic
      review of 32 cases. The significance of anucleate structures on
      immunohistochemistry.
AB  - The sentinel lymph node (SLN) procedure is used in our institute in the setting
      of an observational multicenter study investigating the reliability of the
      sentinel node procedure in vulvar carcinoma (GROINSS-V: The Groningen
      International Study on Sentinel Nodes in Vulvar Cancer). One of our patients had
      a groin recurrence where the SLN had been reported as negative. After reviewing
      this SLN, it contained several anucleate, keratin-positive structures on
      immunohistochemistry, and in the same area on hematoxylin and eosin coloring, one
      single cell with a nucleus interpreted as a tumor cell. Our objective was to
      assess how frequently these anucleate structures occur and whether such nodes
      should be regarded as positive. The sentinel nodes from 32 patients with early
      stage vulvar squamous cell carcinoma were reviewed. Seventy-seven SLN's were
      identified. In ten patients, the SLN was positive and a bilateral inguinofemoral
      lymph node dissection was subsequently performed. In two of these ten patients,
      both with a macrometastasis on SLN, further metastatic disease was present in the
      dissection specimen. Anucleate keratin-positive structures were seen on
      immunohistochemistry in 14 SLN's (18%), usually along with metastasis or single
      tumor cells, but in five nodes this was the only abnormality (mean follow-up
      period of 26.28 months). Anucleate keratin-positive structures are a common
      finding in immunohistochemical examination of SLN's. Our findings suggest that
      they are of no clinical significance and the SLN should be regarded as negative.
      When an atypical cell with a nucleus is present, the SLN should be classified as
      positive and further management should be accordingly.

PMID- 18081795
TI  - The outcome of patients with stage I endometrial cancer involving the lower
      uterine segment.
AB  - The objective of this study was to evaluate whether lower uterine segment
      involvement (LUSI) correlates with recurrence and survival in women with stage I
      endometrial adenocarcinoma and whether it is associated with poor prognostic
      histopathologic features. Three hundred seventy-five consecutive patients with
      endometrial carcinoma stage I compromised the study population. The patients were
      divided into two groups according to the presence of LUSI with endometrial
      carcinoma. The two groups were compared with regard to prognostic factors and
      outcome measures by using the Pearson chi(2) test, log-rank test, and Cox
      proportional hazards model. LUSI was present in 89 (24%) patients with stage I
      endometrial carcinoma. LUSI was significantly associated with grade 3 tumor (P =
      0.022), deep myometrial invasion (P < 0.0001), and the presence of capillary
      space-like involvement (CSLI) (P = 0.003). Kaplan-Meier survival curves
      demonstrated that patients with LUSI had a lower recurrence-free survival (log
      rank test; P = 0.009) and a worse overall survival (log-rank test; P = 0.0008).
      In the Cox proportional hazards model, only a trend toward higher recurrence rate
      (HR = 2.4, 95% CI 0.7, 8.2; P = 0.16) and a trend toward poorer overall survival
      (HR = 1.54, 95% CI 0.82, 2.91; P = 0.18) were noted when LUSI was present. In
      patients with stage I endometrial cancer, the presence of LUSI is associated with
      grade 3 tumor, deep myometrial invasion, and the presence of CSLI. A larger group
      of patients is necessary to conclude whether higher recurrence rate and poorer
      overall survival are associated with the presence of LUSI.

PMID- 18081796
TI  - Multicenter cohort study on treatment results and risk factors in stage II
      endometrial carcinoma.
AB  - The aim of this study was to report outcome data and prognostic factors from a
      large cohort of pathologic stage II endometrioid type endometrial carcinoma. One
      hundred forty-two stage IIA-B patients were included. A central histopathologic
      review was performed. Follow-up ranged from 2 to 217 months with a median of 61
      months. End points of the study were local and locoregional recurrence rates,
      distant metastasis-free survival (DMFS), disease-free survival (DFS), and disease
      specific survival (DSS). The local failure rate was 5.1% for stage IIA patients
      and 10.8% for stage IIB patients. Grade was the only significant prognostic
      factor for local failure. With respect to DMFS, DFS, and DSS, grade 3 showed to
      be the most prominent prognostic factor in multivariate analyses. Lymphvascular
      space involvement combined with grades 3 and 2 and myometrial invasion greater
      than 0.5 also showed to be significant for DMFS and DFS. Our study showed grade 3
      to be the most important single independent predictive factor for locoregional
      and distant recurrences in endometrial carcinoma stage II.

PMID- 18081797
TI  - Anaemia in heart failure: a common interaction with renal insufficiency called
      the cardio-renal anaemia syndrome.
AB  - BACKGROUND: Although many studies have found a high prevalence of anaemia in
      patients with congestive heart failure (CHF), few have carefully examined the
      relationship between the CHF and the prevalence of anaemia and chronic renal
      insufficiency (CRI). Patients with advanced renal failure, significant anaemia,
      diffuse atherosclerosis, respiratory disease and more elderly patients have been
      systematically excluded from the great majority of the randomised clinical
      trials. DISCUSSION: Both anaemia and renal insufficiency are very common
      associated diseases associated with increased mortality, morbidity and rate of
      hospitalisation in CHF patients. Impaired renal function is associated with
      adverse outcomes because it represents a marker of coexistent disease and more
      diffuse atherosclerosis. In patients with CHF, progressive renal dysfunction
      leads to a decrease in erythropoietin (EPO) levels with reduced erythrocyte
      production from bone marrow. This may explain the common association between CHF,
      anaemia and CRI in clinical practice. The normalisation of haemoglobin
      concentration by EPO in patients with CHF and CRI results in improved exercise
      capacity by increasing oxygen delivery and improving cardiac function.
      CONCLUSION: In this review, we describe the mechanisms linking anaemic status,
      CRI and CHF, the prognostic relevance of each disease, treatment implications,
      and potential benefit of EPO administration.

PMID- 18081798
TI  - Hirsutism.
AB  - Hirsutism is defined as the excessive growth of terminal hair on the face and
      body of a female in a typical male pattern distribution. Hirsutism is a common
      clinical problem in women and the treatment depends on the cause of hirsutism.
      Untreated hirsutism can be associated with considerable loss of self-esteem and
      psychological morbidity. Hyperandrogenemia is the key trigger for excess hair
      growth. Polycystic ovary syndrome and idiopathic hirsutism are the most common
      cause of hirsutism. As with all medical problems, investigation begins with a
      careful history, examination and then investigation directed at the possible
      cause. A raised serum testosterone level of > 150 ng/dl (5.2 nmol/l) should
      prompt further investigations to exclude an underlying androgen-secreting tumour.
      The treatment of hirsutism is most effective using combination therapy, including
      lifestyle therapies, androgen suppression, peripheral androgen blockage and
      cosmetic treatments. Women should be warned not to expect improvement or at least
      3-6 months after therapy is begun and lifelong therapy may be needed to prevent
      recurrence. The current review discusses definition, pathogenesis, differential
      diagnosis, diagnostic strategies, management, guidelines and the authors'
      recommendations about hirsutism.

PMID- 18081799
TI  - The clinical value of rapid assay for plasma B-type natriuretic peptide in
      differentiating congestive heart failure from pulmonary causes of dyspnoea.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is a cardiac neurohormone secreted
      from the cardiac ventricles in response to pressure overload. OBJECTIVE: To
      evaluate the optimal cutoff point of plasma BNP in diagnosing congestive heart
      failure (CHF). METHODS: We conducted a prospective study of 195 patients who were
      hospitalised with dyspnoea. Pulmonary capillary wedge pressure (PCWP) was
      measured with a Swan-Ganz catheterisation and plasma BNP level was obtained by a
      rapid immunofluorescence assay in all patients. PCWP >12 mmHg was chosen as the
      golden standard for left ventricular dysfunction in this study. The subjects were
      divided into two groups by the criteria, one group with dyspnoea caused by CHF
      (n=134) and the other caused by lung diseases (n=61). RESULTS: (1) BNP cutoff
      point of 100 pg/ml had a sensitivity of 94.34%, a specificity of 92.13% and an
      accuracy of 93.33% for differentiating CHF from pulmonary dyspnoea. (2) By
      multiple logistic-regression analysis, measurements of BNP added significantly
      independent predictive power to other clinical variables in models predicting
      which patients had CHF. CONCLUSION: A value of 100 pg/ml or more for a rapid BNP
      assay may be the most accurate independent predictor of the presence or absence
      of CHF.

PMID- 18081800
TI  - Massage therapy for the treatment of depression: a systematic review.
AB  - BACKGROUND: People with depressive disorders or subsyndromal symptoms of
      depression (SSD) often use complementary and alternative therapies, including
      massage therapy (MT). This systematic review evaluates the evidence, from
      randomised clinical trials (RCTs), for the effectiveness of multiple sessions of
      classical European (Swedish) MT for the treatment of depression. METHODS:
      Eligible RCTs were identified via eight electronic databases and manual searches
      of references. Two reviewers independently selected trials, assessed trial
      quality and extracted data. RESULTS: Four RCTs met our inclusion criteria. Three
      of these RCTs compared MT with relaxation therapies, but provided insufficient
      data and analyses to contribute meaningfully to the evaluation of MT for
      depression. The fourth included RCT used MT as a control condition to evaluate a
      depression-specific acupuncture treatment. This trial provided limited evidence
      that, in the early stages of treatment, MT is less effective than acupuncture for
      treating depression, a treatment which itself is not accepted for this condition.
      CONCLUSIONS: Despite previous research suggesting that MT may be an effective
      treatment for depression, there is currently a lack of evidence to support this
      assertion from RCTs that have selected participants for depression or SSD.

PMID- 18081801
TI  - In vivo models for early development of colorectal liver metastasis.
AB  - In Europe, colorectal cancer is the second most prevalent form of cancer
      diagnosed. Globally each year, almost one million cases of colorectal cancer are
      registered and almost half a million deaths are attributed to this disease. This
      high mortality is associated with the development of liver metastases. For
      oncological advances to occur, accurate in vivo models are required to study
      colorectal cancer metastasis development. These models, by increasing our
      understanding of the early stages of colorectal liver establishment, will
      facilitate the development of novel therapeutic interventions and allow the
      clinical effects of these interventions to be studied. By analysis of current in
      vivo models for early development of colorectal liver metastasis, this review
      examines available methods of the tumour cell preparation, introduction and
      monitoring in vivo. An insight into the technical problems which can occur will
      be discussed. The implications of these different techniques on the resulting
      metastasis picture will be analysed. Existing in vivo models are assessed
      regarding the accuracy of the metastatic picture they portray.

PMID- 18081802
TI  - Replantation of three avulsed permanent incisors with complicated crown
      fractures.
AB  - AIM: To report a rare case of multiple avulsions of permanent teeth associated
      with complicated crown fractures. SUMMARY: The case describes a 3-year follow-up
      of the treatment of three avulsed maxillary incisors with complicated crown
      fractures. The teeth were replanted after an extra-oral time of 90 min (extra
      oral dry time 6 min). After root canal treatment, the fractured maxillary
      incisors were restored with a layered hybrid composite material to re-establish
      aesthetics and function. Follow-up visits showed signs of replacement resorption
      affecting the maxillary central incisors but only minor signs of root resorption
      on the maxillary right lateral incisor. These findings were supported by digital
      volume tomography, which was performed 18 and 36 months post-trauma in order to
      assess extent, severity and progression of root resorption more accurately.
      *Healing of avulsed teeth depends on the degree of periodontal ligament (PDL)
      damage. *Digital volume tomography might improve diagnostics of root resorption.

PMID- 18081803
TI  - Canal preparation using only one Ni-Ti rotary instrument: preliminary
      observations.
AB  - AIM: To describe a novel canal preparation technique using only one Ni-Ti rotary
      instrument. SUMMARY: In this novel technique, the canal is negotiated to the
      working length with a size 08 hand file. Then, the canal preparation is completed
      with an F2 ProTaper instrument used in a reciprocating movement. In larger
      canals, the use of additional hand files may be required to complete the apical
      enlargement. *A novel canal preparation technique is introduced using only one Ni
      Ti rotary instrument in a reciprocating movement. *The advantages of the
      technique include a reduced number of instruments, lower cost, a reduced
      instrument fatigue and the elimination of possible prion cross-contamination
      associated with the single use of endodontic instruments.

PMID- 18081804
TI  - Efficacy of ProTaper Universal rotary retreatment system for gutta-percha removal
      from root canals.
AB  - AIM: To evaluate the efficacy of the ProTaper Universal rotary retreatment system
      for gutta-percha (GP) removal from root canals. METHODOLOGY: Root canals of 60
      extracted human maxillary anterior teeth were prepared and filled with laterally
      condensed GP and AH Plus sealer. Teeth were divided into three groups: group A-
      GP removal completed with the ProTaper Universal rotary retreatment system and
      with further canal repreparation accomplished with ProTaper Universal rotary
      instruments; group B--GP removal was completed using Gates Glidden drills and
      Hedstrom files with chloroform as a solvent, followed with further canal
      repreparation with ProTaper Universal rotary instruments; group C--the same as
      group B for GP removal with further canal preparation with stainless steel K-flex
      files (Kerr). The operating time was recorded. Teeth were rendered transparent
      for the evaluation of the area of remaining GP/sealer in bucco-lingual and mesial
      distal directions. Statistical analysis was performed by using repeated measures
      analysis of variance and anova. Results The ProTaper Universal technique (group
      A) resulted in a smaller percentage of canal area covered by residual GP/sealer
      than in groups B and C, with a significant difference between groups A and C (P <
      0.05). Mean operating time for group A was 6.73 min, which was significantly
      shorter (P < 0.05) than group B (10.86 min) and group C (13.52 min). CONCLUSIONS:
      In this laboratory study all test techniques left GP/sealer remnants within the
      root canal. The ProTaper Universal rotary retreatment system proved to be an
      efficient method of removing GP and sealer from maxillary anterior teeth.

PMID- 18081805
TI  - Antimicrobial activity of various 'active' gutta-percha points against
      Enterococcus faecalis in simulated root canals.
AB  - AIM: To test the antimicrobial activity of various gutta-percha points against
      Enterococcus faecalis in simulated root canals. METHODOLOGY: Root canals were
      simulated by inoculated glass capillaries. A 2.5 microL increment of a suspension
      of E. faecalis was placed into 10 simulated root canals together with Calcium
      Hydroxide(R) points (CHP), Calcium Hydroxide Plus(R) points (CH+P), active
      points(R) (AP), conventional gutta-percha points (CP) (Coltene Whaledent,
      Langenau, Germany) or no points (NP) (control) (each n = 2). The points and
      simulated root canals were flushed with 2 mL of sterile saline solution after 10
      min or after 5 h of anaerobic incubation (37 degrees C, 100% humidity). Dilution
      sequences until 10(-3) and 10(-4) were prepared and plated on agar plates. The
      original suspension, diluted until 10(-6) and 10(-7), served as another control.
      The numbers of colony forming units were counted after 24 h. This experimental
      procedure was repeated 15 times. RESULTS: Without gutta-percha points, bacteria
      grew threefold in number within 5 h. With CHP and CH+P bacterial counts at 10 min
      and 5 h were approximately 50% compared with the control. AP killed all bacteria
      within 5 h. With CP, bacteria proliferated more than without points (counts at 5
      h 177% of NP). Except for CHP versus CH+P differences between groups were
      statistically significant (Mann-Whitney test, P < 0.01). CONCLUSIONS: In this
      experimental model, the potential of CHP and CH+P to kill E. faecalis was
      limited. CP stimulated bacterial growth. AP killed all bacteria after 5 h.

PMID- 18081806
TI  - Root form and canal morphology of mandibular premolars in a Jordanian population.
AB  - AIM: To investigate the root canal anatomy of mandibular premolars in a Jordanian
      population. METHODOLOGY: Nine hundred extracted mandibular premolars were
      examined. After the length of the teeth was measured, the presence of
      developmental grooves and furcated roots was noted. Following the preparation of
      access cavities, pulp tissue was removed and the canal systems were stained. The
      teeth were then rendered clear by demineralization and immersion in methyl
      salicylate. Cleared teeth were examined and the following features were
      evaluated: (i) type of root canals; (ii) presence and location of lateral canals;
      transverse anastomosis; (iii) location of apical foramina; and (iv) frequency of
      apical deltas. RESULTS: The mean lengths of first and second mandibular premolars
      were 22.6 mm (18-27.5 mm) and 22.2 mm (16-26.5 mm), respectively. Although the
      majority of the specimens corresponded to Vertucci's classification scheme,
      analysis of this large data set revealed four additional root canal morphologies.
      Variable root canal morphologies were found in the mandibular first premolars;
      two separate apical foramina were found in 33% of the teeth with two canals,
      compared to 6.2% with one apical foramen. Teeth with three separate apical
      foramina were scarce (2.2%). The majority of the mandibular second premolars had
      a single canal; 72% of teeth possessed type I canal systems, whilst 22.8% of the
      roots had two canals with two separate apical foramina. CONCLUSIONS: The
      prevalence of multiple canals in the investigated Jordanian mandibular premolars
      was high, especially for the second mandibular premolar, in comparison with
      previous studies performed on populations of different racial origin.

PMID- 18081807
TI  - Micropush-out bond strengths of gutta-percha versus thermoplastic synthetic
      polymer-based systems - an ex vivo study.
AB  - AIM: To compare the interfacial strength and failure mode of root fillings
      consisting of different technique-material combinations. METHODOLOGY: Human
      mandibular premolars (n = 144) instrumented to apical size 40 and .06 taper were
      divided into 12 experimental groups. The root canals were filled with either
      gutta-percha (groups 1-6) or Resilon (groups 7-12) core materials combined with
      AH Plus (groups 1, 4, 7, 10), Ketac-Endo (groups 2, 5, 8, 11) or Epiphany (groups
      3, 6, 9, 12) using cold lateral compaction (groups 1-3, groups 7-9) or System B
      with Obtura II (groups 4-6, groups 10-12). Three serial 1.00 +/- 0.05-mm-thick
      root slices were prepared and push-out tests on the filling material were
      performed. Interactions amongst the compaction techniques, core materials and
      sealers were analysed using a three-way analysis of variance (anova) (P < 0.05).
      One-way anova and Duncan's Multiple Range tests were used to compare the bond
      strengths of the 12 groups. Fracture modes of all root slices were evaluated
      stereomicroscopically at x40 magnification. RESULTS: All the parameters except
      compaction techniques had significant interactions (P < 0.05). A significant
      difference was found amongst the groups (P < 0.05). Gutta-percha/Ketac-Endo/cold
      lateral compaction and gutta-percha/AH Plus/cold lateral compaction groups had
      the highest micropush-out bond strength values (P < 0.05). The number of overall
      cohesive failures was significantly more than that of adhesive failures (P <
      0.05). CONCLUSIONS: The push-out bond strengths of Resilon/Epiphany combinations
      were lower than those of gutta-percha/conventional root canal sealer
      combinations. Core materials and sealers may affect the push-out bond strengths
      of root canal filling materials.

PMID- 18081808
TI  - Effect of photo-activated disinfection on endodontic pathogens ex vivo.
AB  - AIM: To test the hypothesis that photo-activated disinfection (PAD) has a
      bactericidal effect on pathogens inoculated in root canals, with emphasis on
      biofilm formation/destruction. METHODOLOGY: Root canals of extracted teeth (n =
      38) were prepared (size 30, 0.10 taper), autoclaved, divided into three groups
      and two negative controls inoculated (Streptococcus anginosus, Enterococcus
      faecalis or Fusobacterium nucleatum) and treated (PAD, laser, dye or positive
      control) according to a cross-sectional design. Resultant colony-forming unit
      counts were associated with observations of cell structural changes using
      environmental scanning electron microscopy (ESEM) on inoculated dentinal surfaces
      (n = 22, two controls) before (1, 2 and 6 days of incubation) and after treatment
      with PAD. RESULTS: Treatment of root canals with PAD (15 J) caused a significant
      reduction of the bacterial load, resulting in a 93.8% kill of S. anginosus (P <
      0.0001), a 88.4% kill of E. faecalis (P < 0.05) and a 98.5% kill of F. nucleatum
      (P < 0.0001), but no sterilization. Laser alone had no significant effect on the
      load nor did the dye without laser. The ESEM experiment showed that individual
      cells or monolayers were easily eliminated with PAD. But when biofilms were
      present (2 and 6 days for E. faecalis, 6 days for S. anginosus), bacterial
      eradication was substantially reduced in deep layers. CONCLUSIONS: Photo
      activated disinfection is not an alternative but a possible supplement to the
      existing protocols for root canal disinfection as the interaction between light
      (diode laser) and associated dye (TBO) provides a broad-spectrum effect. Some
      endodontic pathogens that grow as single-species biofilms, however, are difficult
      to eradicate.

PMID- 18081809
TI  - Thermal transfer in extracted incisors during thermal pulp sensitivity testing.
AB  - AIM: To measure the temperature distribution within tooth structure during and
      after application of thermal stimuli used during pulp sensitivity testing.
      METHODOLOGY: Extracted intact human maxillary anterior teeth were investigated
      for temperature changes at the labial enamel, the dentino-enamel junction (DEJ)
      and pulpal surface during and after a 5-s application of six different thermal
      stimuli: hot water (80 degrees C), heated gutta-percha (140 degrees C), carbon
      dioxide dry ice (-72 degrees C), refrigerant spray (-50 degrees C), ice stick (0
      degrees C) and cold water (2 degrees C). J-type thermocouples and heat conduction
      paste were used to detect temperature changes, together with a data acquisition
      system (Labview). Data were analysed using analysis of variance, with a
      confidence level of P < 0.05. RESULTS: Temperature change was detected more
      quickly at the DEJ and pulpal surface with the application of hot water, heated
      gutta-percha and refrigerant spray than with carbon dioxide dry ice and ice (P <
      0.05). Cold water and refrigerant spray were in the same range in terms of time
      to detect temperature change at both the DEJ and pulpal surface. Thermal stimuli
      with greater temperature difference from tooth temperature created a greater
      thermal gradient initially, followed by a greater temperature change at the DEJ
      and the pulpal surface. In this regard, ice and cold water were weaker stimuli
      than others (P < 0.05). CONCLUSIONS: Thermal stimuli used in pulp testing are
      highly variable in terms of temperature of the stimulus, rate of thermal transfer
      to the tooth and extent of temperature change within tooth structure. Overall,
      dry ice and refrigerant spray provide the most consistent stimuli, whereas heated
      gutta-percha and hot water were highly variable. Ice was a weak stimulus.

PMID- 18081810
TI  - Gingival and bone necrosis caused by accidental sodium hypochlorite injection
      instead of anaesthetic solution.
AB  - AIM: To report clinical complications (pain, necrotic gingival tissue and bone
      sequestration) resulting from accidental injection of sodium hypochlorite.
      SUMMARY: Root canal treatment is a routine clinical procedure with few reported
      complications. Sodium hypochlorite (NaOCl) is commonly used as an irrigant during
      the procedure because of its tissue-dissolving, antibacterial and lubricating
      properties. This paper presents a case in which accidental injection of sodium
      hypochlorite into the lingual gingiva of a female patient caused gingival and
      bone necrosis. Surgical intervention was required. KEY LEARNING POINTS: *Sodium
      hypochlorite is dangerous if injected into the tissues. *The presentation of
      sodium hypochlorite in glass, anaesthetic type cartridges is potentially
      dangerous, and should be condemned. *All healthcare workers should check
      carefully the contents of any syringe before injecting into patients.

PMID- 18081811
TI  - Hydrogen peroxide induces expression and activation of AMP-activated protein
      kinase in a dental pulp cell line.
AB  - AIM: To investigate the effects of hydrogen peroxide on cell viability and
      expression and activation of AMP-activated protein kinase (AMPK) in rat dental
      pulp cell line RPC-C2A. METHODOLOGY: RPC-C2A cells derived from rat dental pulp
      were maintained in MEM supplemented with 10% FBS at 37 degrees C, in a humidified
      atmosphere at 5% CO(2). Cells were cultured in the presence or absence of
      H(2)O(2) for up to 60 min at concentrations of from 0.1 to 3.0 mmol L(-1). Cell
      viability was analysed by WST-1 reduction assay. Expression of AMPK subunit
      isoforms was analysed by Western blotting using antibodies to the catalytic
      alpha1 and regulatory beta1 and gamma1 subunit isoforms. The effect of silencing
      AMPKalpha1 on cell viability was determined using siRNA. RESULTS: Exposure to
      H(2)O(2) decreased cell viability in a time- and dose-dependent manner. The
      catalytic AMPKalpha1 subunit and its activated form, phospho-AMPKalpha, increased
      with exposure to H(2)O(2) in a time- and dose-dependent manner, whereas the
      regulatory beta1 and gamma1 subunits showed no change. Downregulation of
      AMPKalpha1 resulted in a reduction in cell viability in H(2)O(2)-treated cells at
      a concentration of 0.1 mmol L(-1) for 30 min incubation, indicating an increased
      sensitivity to H(2)O(2). CONCLUSIONS: Reactive oxygen induced energy fuel gauge
      enzyme AMPKalpha expression and its activation by phosphorylation in RPC-C2A
      cells, suggesting that AMPK is essential for protection against H(2)O(2)-induced
      nonapoptotic cell death. Therefore, AMPK may be a therapeutic modulation target
      for treatment of the dentine-pulp complex injured by reactive oxygen.

PMID- 18081812
TI  - Efficacy of three rotary NiTi instruments in removing gutta-percha from root
      canals.
AB  - AIM: To investigate the ability of three rotary nickel-titanium instruments and
      hand instrumentation to remove gutta-percha and sealer. METHODOLOGY: Sixty
      freshly extracted human single-rooted teeth, each with one root canal, were
      instrumented with K-files and filled using cold lateral compaction of gutta
      percha and AH Plus (Dentsply Detrey, Konstanz, Germany) sealer. The teeth were
      randomly divided into four groups of 15 specimens each. Removal of gutta-percha
      was performed with the following devices and techniques: ProTaper, R-Endo, Mtwo
      and Hedstrom files. The specimens were rendered transparent and the area of
      remaining filling material on the root canal wall was measured using a computer
      image analysis program. Statistical analysis was accomplished by Kruskal-Wallis
      and Mann-Whitney U-tests with Bonferroni correction for the analysis of residual
      root filling material and working time. RESULTS: The ProTaper group had less
      filling material inside the root canals than the other groups, but a significant
      difference was found between only the ProTaper and Mtwo groups (P < 0.05). The
      retreatment time for Mtwo and ProTaper was significantly shorter compared with R
      Endo and manual instrumentation with Hedstrom files (P < 0.001). R-Endo was
      significantly faster than manual instrumentation (P < 0.001). CONCLUSIONS: Under
      the experimental conditions, ProTaper left significantly less gutta-percha and
      sealer than Mtwo instruments. Complete removal of materials did not occur with
      any of the instrument systems investigated.

PMID- 18081813
TI  - Resection margins and R1 rates in pancreatic cancer--are we there yet?
AB  - The prognosis of pancreatic cancer is poor, even for those patients who undergo
      surgical resection. The rate of local recurrence is high, despite the fact that
      in most series complete ('R0') resection is reported to be achieved in the
      majority of patients. The discrepancy between pathological assessment and
      clinical outcome indicates that microscopic margin involvement (R1) is frequently
      underreported, and potential causes for this are discussed in this review.
      Special emphasis is given to the variation that exists between currently used
      dissection techniques and their impact on the assessment of the resection margins
      in pancreatoduodenectomy specimens.

PMID- 18081814
TI  - Progesterone receptor reactivity in renal oncocytoma and chromophobe renal cell
      carcinoma.
AB  - AIMS: To investigate the reactivity for oestrogen and progesterone receptors (ER
      and PR) in renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC).
      MATERIALS AND METHODS: Thirty-eight RO, 25 CHRCC, 20 papillary RCC with oncocytic
      cytoplasm and 10 clear cell RCC with dominant eosinophilic cytoplasm were
      submitted for immunohistochemistry for ER, PR, CD117 and RCC. RESULTS: All cases
      of RO and CHRCC displayed moderately positive reactivity for PR. The nuclear
      reactivity ranged from 60% to 90% in RO and from occasional cells to 70% in
      CHRCC. In CHRCC, reactivity tended to be more prevalent in areas of tumour cells
      with eosinophilic cytoplasm. Progesterone reactivity was focal in areas. All RO
      and most CHRCC were reactive for CD117 and neither RO nor CHRCC was reactive for
      RCC. CD117 reactivity tended to be more intense in CHRCC than in RO. Negative
      reactivity for CD117 and positive reactivity for RCC were observed in almost all
      RCC, as reported in the literature. CONCLUSIONS: PR can be used in combination
      with CD117 and RCC in the differential diagnosis of RO and eosinophilic variant
      of CHRCC with other RCC with oncocytic or eosinophilic cytoplasm.

PMID- 18081815
TI  - Alpha-methylacyl-CoA racemase (AMACR) immunohistochemistry in Barrett's and
      colorectal mucosa: only significant overexpression favours a diagnosis of
      intraepithelial neoplasia.

PMID- 18081816
TI  - A giant myxoid mammary myofibroblastoma: evidence for a myogenic/synthetic
      phenotype and an extracellular matrix rich in fibronectin.

PMID- 18081817
TI  - Grading of serous ovarian carcinoma: further evidence of a lack of agreement
      between conventional grading systems.

PMID- 18081818
TI  - CD10 is a characteristic marker of tumours forming morules with biotin-rich,
      optically clear nuclei that occur in different organs.

PMID- 18081819
TI  - Psychiatric symptoms in children and adolescents with cyclic vomiting syndrome
      and their parents.
AB  - OBJECTIVE: To conduct a pilot study to evaluate the prevalence of psychiatric
      symptoms in children and adolescents with cyclic vomiting syndrome and to assess
      family history of psychiatric disorder. BACKGROUND: Little is known about
      psychiatric comorbidity in youth with cyclic vomiting syndrome, a periodic
      syndrome. METHODS: Eighty-five parents, of children aged 3-18 years with cyclic
      vomiting syndrome confirmed in a multidisciplinary clinic, completed the age
      appropriate Children's Symptom Inventory, a questionnaire that screens for
      psychiatric symptoms in pediatric patients. Twenty-one adolescents aged 13-18
      years completed the Youth's Report, a self-report form of this questionnaire.
      Sixty-two parents completed a family psychiatric history checklist. RESULTS:
      These children and their parents evidenced a high prevalence of anxiety and mood
      symptoms compared to norms of the Children's Symptom Inventory and population
      norms for internalizing psychiatric disorders. On the age-appropriate Children's
      Symptom Inventory, 47% of subjects (40/85) met diagnostic cut-off for an anxiety
      disorder, and 14% (12/85) for an affective disorder. Discrepancies were found in
      parent and adolescent reports for symptoms of panic disorder (chi-square = 4.83,
      df = 1, P = .028), posttraumatic stress disorder (chi-square = 6.87, df = 1, P =
      .009), and somatization disorder (chi-square = 6.41, df = 1, P = .01), with
      parents reporting significantly more symptoms than the adolescents. Internalizing
      disorders were also prevalent in the parents with 59% (36/62) endorsing either an
      anxiety and/or an affective disorder. Mothers reported a significantly higher
      prevalence of anxiety disorders (35%) than did fathers (13%) (chi-square = 8.43,
      df = 1, P < .004). CONCLUSION: Children and adolescents with cyclic vomiting
      syndrome appear to be at increased risk for internalizing psychiatric disorders,
      especially anxiety disorders. Further research using standardized psychiatric
      interviews and a control group are indicated to further assess psychiatric
      disorders in children and adolescents with cyclic vomiting syndrome.

PMID- 18081820
TI  - Behavioral dependence in patients with medication overuse headache: a cross
      sectional study in consulting patients using the DSM-IV criteria.
AB  - OBJECTIVE: The aim of this study was to assess behavioral dependence on migraine
      abortive drugs in medication-overuse headache (MOH) patients and identify the
      predisposing factors. BACKGROUND: It is common occurrence that MOH patients
      relapse after medication withdrawal. Behavioral determinants of medication
      overuse should therefore be identified in MOH patients. METHODS: This was a cross
      sectional, multicenter study that included 247 MOH patients (according to
      International Classification of Headache Disorders, 2nd edition criteria)
      consulting in French headache specialty centers. Face-to-face interviews were
      conducted by senior neurologists using a structured questionnaire including the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)
      criteria for the evaluation of dependence, Hospital Anxiety and Depression Scale
      for the evaluation of anxiety and depression, and 6-item short-form Headache
      Impact Test scale for the determination of functional impact. RESULTS: Most MOH
      patients had pre-existing primary migraine (87.4%) and current migraine-type
      headaches (83.0%). Treatments overused included triptans (45.8%), opioid
      analgesics alone or in combination (43.3% of patients), and analgesics (27.9%).
      Nonmigraine abortive substances (tobacco, caffeine, sedatives/anxiolytics) were
      overused by 13.8% of patients. Two-thirds of MOH patients (66.8%) were considered
      dependent on acute treatments of headaches according to the DSM-IV criteria. Most
      dependent MOH patients had migraine as pre-existing primary headache (85.7%) and
      current migraine-type headaches (87.9%), and most of them overused opioid
      analgesics. More dependent than nondependent MOH patients were dependent on
      psychoactive substances (17.6% vs 6.1%). Multivariate logistic analysis indicated
      that risk factors of dependence on acute treatments of headaches pertained both
      to the underlying disease (history of migraine, unilateral headaches) and to drug
      addiction (opioid overuse, previous withdrawal). Affective symptoms did not
      appear among the predictive factors of dependence. CONCLUSION: In some cases, MOH
      thus appears to belong to the spectrum of addictive behaviors. In clinical
      practice, behavioral management of MOH should be undertaken besides
      pharmacological management.

PMID- 18081821
TI  - Acute and interictal allodynia in patients with different headache forms: an
      Italian pilot study.
AB  - OBJECTIVE: To investigate allodynia in patients with different primary headaches.
      BACKGROUND: Many migraineurs have allodynia during headache attacks; some may
      have allodynia outside attacks; allodynia may also be associated with other
      primary headaches. METHODS: A total of 260 consecutive primary headache patients
      presenting for the first time at a headache center, and 23 nonheadache controls
      answered written questions (subsequently repeated verbally) to determine the
      presence of acute and interictal allodynia. RESULTS: We divided the patients
      into: episodic migraine (N = 177), subdivided into only migraine without aura (N
      = 114) and those sometimes or always reporting migraine with aura (N = 63);
      episodic tension-type headache (N = 28); chronic headaches (headache > or = 15
      days/month, N = 52), including chronic migraine, chronic tension-type headache,
      and medication-overuse headache; and other headache forms (N = 3). Acute
      allodynia was present in 132 (50.7%), significantly more often in patients
      sometimes or always suffering migraine with aura, and those with chronic headache
      forms, compared to patients with migraine without aura and episodic tension-type
      headache. Interictal allodynia was present in 63 (24.2%) patients, with
      significantly higher frequency in those having migraine with aura attacks than
      controls and common migraine patients. CONCLUSIONS: Allodynia is not specific to
      migraine but is frequent in all headache patients: acute allodynia was reported
      in half those interviewed and in over a third of patients in each headache
      category; interictal allodynia was reported by nearly 25%.

PMID- 18081822
TI  - Recurrent headache due to MS plaque.

PMID- 18081824
TI  - Lifetime basilar migraine: a pontine syndrome?
AB  - We describe the clinical and radiological findings of an 82-year-old woman
      patient with basilar type migraine attacks occurring over 70 years with a similar
      pattern of intensity and symptoms. We provide some evidence to suggest that
      gradual development of calcifications in the pontine tegmental nuclei can trigger
      attacks of basilar type migraine.

PMID- 18081825
TI  - Hypnic headache responsive to low-dose topiramate: a case report.
AB  - This is a clinical report of a 63-year-old woman, with a 3-year history of severe
      episodes of hypnic headache responding to low-doses of topiramate (25 mg at
      bedtime). Topiramate has been used at the dosage of 100 mg/day for hypnic
      headache prevention in one recent case report with benefit. This report confirms
      the efficacy of topiramate in hypnic headache even using low-dose regimen
      therapy.

PMID- 18081823
TI  - Phenotypic and genetic analysis of a large family with migraine-associated
      vertigo.
AB  - OBJECTIVES: To describe a large multigenerational family with migraine-associated
      vertigo (MAV) combining a detailed phenotypic and genetic analysis. BACKGROUND:
      Migraine-associated vertigo is said to be highly prevalent in the general
      population and, like other migraine syndromes, its etiology is felt to have a
      strong genetic component. However, so far, there have been no reports of large
      families with MAV. METHODS: Detailed clinical study was conducted on a large
      multigenerational family with MAV. Genetic study using identical-by-descent
      analysis with dense single nucleotide polymorphism (SNP) arrays was performed to
      examine consistent inheritance pattern among the affecteds. RESULTS: Clinical
      features of MAV were variable although most had other migraine symptoms with at
      least some of their attacks. We did not find a region of the genome shared by all
      eight subjects with MAV indicating a polygenetic inheritance for MAV even in this
      single large family. CONCLUSIONS: A region on 11q shared by most affected females
      may contain a susceptibility allele for MAV that is expressed exclusively or
      predominantly by women.

PMID- 18081826
TI  - The use of factor VIII/von Willebrand factor concentrate for immune tolerance
      induction in haemophilia A patients with high-titre inhibitors: association of
      clinical outcome with inhibitor epitope profile.
AB  - A retrospective chart review of 11 subjects with severe haemophilia A and high
      titre inhibitors who received a von Willebrand factor-containing FVIII
      concentrate (VWF/FVIII) for immune tolerance induction (ITI) was accompanied by B
      cell inhibitor epitope mapping during 10/11 treatment courses. ITI was successful
      or partially successful in all seven subjects who received VWF/FVIII for initial
      ITI, and failed in all four subjects whose ITI with this product was initiated
      following treatment failure using recombinant factor VIII. Variables including
      age at inhibitor development and age at ITI initiation, interval between
      inhibitor detection and ITI initiation, titre at start of ITI, and peak
      historical titres prior to and during ITI were not statistically significant
      outcome predictors in this cohort. However, the B cell epitope specificity in all
      four successful and in one of two partially successful ITI subjects for whom
      information was available included the C2 and excluded the A2 domains.
      Conversely, FVIII B cell epitopes in one partially successful ITI and in all
      three failed ITI subjects for whom data were available mapped to both the C2 and
      the A2 domains. The FVIII B cell epitope profile was associated with ITI outcome
      in this VWF/FVIII-treated cohort. Its role in predicting ITI outcome and guiding
      choice of FVIII product for ITI requires further study.

PMID- 18081827
TI  - Recombinant activated factor VII for haemophilia patients with inhibitors
      undergoing orthopaedic surgery: a review of the literature.
AB  - Arthropathy is prevalent in patients with haemophilia and inhibitors and is a
      major source of pain and disability, significantly reducing quality of life.
      Recombinant activated factor VII (rFVIIa; NovoSeven is one of the treatments
      available for acute life-threatening bleeding episodes in haemophilia patients
      with inhibitors. It has also been used successfully in a range of orthopaedic
      surgical procedures in these patients. This is a review of published data on
      elective orthopaedic procedures in haemophilia patients with inhibitors under
      cover of rFVIIa from January 2002 to November 2006. Articles were retrieved from
      MEDLINE using specified search parameters. Twelve articles covering a total of 80
      orthopaedic procedures were identified. In the vast majority of cases, rFVIIa
      provided safe and effective haemostatic cover during orthopaedic surgery with no
      bleeding complications. There was variation in the administered dose, although
      the majority of patients were treated with 90 mug kg(-1) bolus followed by either
      continuous infusion or bolus infusion. Of those cases reporting bleeding
      complications, most were considered to be related to an inadequate amount of
      rFVIIa. The cumulative experience presented here suggests that rFVIIa is safe and
      effective for providing adequate haemostatic cover for haemophilia patients with
      inhibitors undergoing orthopaedic surgery. The optimal dosing regimen and mode of
      administration has yet to be identified. Further controlled trials are needed to
      confirm these experiences.

PMID- 18081828
TI  - Protecting the joints of mice and men.

PMID- 18081830
TI  - Low-dose immune tolerance induction for paediatric haemophilia patients with
      factor VIII inhibitors.
AB  - The development of an inhibitor against factor VIII (FVIII) is a serious
      complication in children with haemophilia A. Immune tolerance induction (ITI)
      therapy is generally considered to be the best approach to eradicate the
      inhibitor. In this paper, the low-dose (< or =50 IU kg(-1) twice or three times
      weekly with plasma-derived factor concentrates) ITI regimen used in Turkey is
      discussed. This regimen was given to 21 haemophilia A patients with high titer
      inhibitors. The median age at the beginning of ITI was 9 years and exposure days
      were 25. The median pre-ITI historical peak inhibitor titer, and inhibitor titer
      when ITI started were 80 BU (range 6.0-517), 19.2 BU (range 3.6-515),
      respectively. Complete immune tolerance was defined as the time at which at least
      two negative inhibitor assays was obtained with no anamnestic response. Our two
      cases were not reached in follow-up period. Immune tolerance could be achieved in
      5 of 19 (26.3%) patients within a median time of 6 months. Partial tolerance was
      obtained in 7 patients while treatment failed in spite of significant decreased
      inhibitor levels in the other patients. A relapse developed in one immune
      tolerized patient, one year later. The level of inhibitor titer at the beginning
      of ITI (< or =10 BU), the pre-ITI historical peak inhibitor titer (<50 BU), and
      the time between the first diagnosis inhibitor to starting ITI (<12 months) were
      main factors in the success (complete or partial tolerance) of ITI. In
      conclusion, the outcome of low-dose ITI protocol was not satisfactory in this
      retrospective study.

PMID- 18081829
TI  - A web-based registry of inherited bleeding disorders in the region of Emilia
      Romagna: results at three and a half years.
AB  - A Registry of inherited bleeding disorders was set up in the Region of Emilia
      Romagna (RER) to collect information about these diseases and to improve the
      quality of care. From January 2003, the eight Haemophilia Centres (HC) in the RER
      began to use computerized clinical records; every 6 months, they send data to
      Parma Hospital to be processed and published in a website
      (http://www.registroemofiliarer.it). Great efforts are made to ensure high
      quality of data. Results of general interest are included in a free 'public area'
      and more sensitive data in a 'reserved area' (open only to HC and to health
      authorities). A total of 610 individuals are included: 249 haemophilia A (HA), 63
      haemophilia B (HB), 173 von Willebrand's disease, 69 rare bleeding disorders,
      seven platelet disorders and 49 haemophilia carriers; 131 were genotyped, 188
      were tested for inhibitors (16 affected). The most frequent bleeding was
      haemarthrosis. The joint score (evaluated in 104 haemophiliacs) was higher in
      severe HA. There were 22 HIV-positive and 182 hepatitis C virus-positive patients
      (21% have chronic hepatitis, two hepatocellular carcinoma). In 2005, two patients
      received primary prophylaxis, 47 secondary prophylaxis, four children were on
      immune-tolerance induction. From 2003 to 2005 the use of recombinant products was
      greatly increased and the majority of patients received them. The mean clotting
      factor consumption for prophylaxis was higher than on-demand treatment. The main
      features of registry are to collect high quality and comprehensive data of all
      patients followed by HC, to improve quality of care and it's availability on the
      web.

PMID- 18081831
TI  - Increased frequency of the CTLA-4 49 A/G polymorphism in patients with acquired
      haemophilia A compared to healthy controls.
AB  - Acquired haemophilia (AH) is an autoimmune disorder characterized by
      autoantibodies against endogenous factor VIII (FVIII). Half of the patients
      present with an underlying disease known to cause the FVIII autoantibodies
      whereas in the other half the disease is of idiopathic nature. Recently, it has
      been shown that variants of the polymorphic cytotoxic T lymphocyte antigen-4
      (CTLA-4) gene are associated with autoimmune diseases and also represent a risk
      factor for inhibitor formation in inherited haemophilia A. In the present study,
      we investigated whether CTLA-4 variants also play a role in the pathogenesis of
      AH. Therefore, we analyzed three single nucleotide polymorphisms (SNPs) of the
      CTLA-4 gene (-318 C/T, +49 A/G and CT60 A/G) in 57 AH patients and 98 controls.
      The CTLA-4 + 49 G allele occurred with a significantly higher frequency in
      patients with AH compared with controls [odds ratio (OR) = 2.17, 95% confidence
      interval (CI): 1.36-3.48, P = 0.001]. This effect was mainly caused by a higher
      frequency of the 49 G allele in female patients (OR = 5.1, 95% CI: 1.76-15.02, P
      = 0.002), whereas in males the frequencies were not significantly different (OR =
      1.4, P = 0.5). A higher frequency of the G allele was also observed in the
      subcohort with AH and underlying autoimmune disease (OR = 3.1, P = 0.04). Our
      observations of a higher frequency of the CTLA-4 + 49 A/G SNP in AH patients are
      in concordance with findings in other autoimmune disorders. In conclusion, on the
      background of the CTLA-4 gene polymorphism, further genetic and/or environmental
      factors might contribute to and finally trigger the clinical manifestation of AH.

PMID- 18081832
TI  - Posturographic analysis of balance control in patients with haemophilic
      arthropathy.
AB  - Musculoskeletal disorders in haemophiliacs represent the highest percentage of
      lesions, giving rise to haemophilic arthropathy (HA) which predominantly affects
      lower limbs, influencing postural control, standing and walking. Leading a
      sedentary lifestyle seems to influence strength and muscular resistance in
      haemophiliacs which, in turn, are related to articular stability and the
      prevention of articular degenerative processes. The objective of this work was to
      study alterations in balance to subsequently evaluate the appropriate
      therapeutics and how this influences the development of arthropathy. Twenty-five
      haemophiliacs with HA, 25 haemophiliacs without HA (NHA) and 25 healthy control
      subjects (CTL) took part in this study. Tests were performed on a force platform
      and the subjects remained as still as possible for 30 s under different
      conditions: (i) bilateral stance with eyes open; (ii) bilateral stance with eyes
      closed; (iii) right unilateral stance; and (iv) left unilateral stance. The
      results of these tests indicated significant differences (P < 0.05) between the
      groups HA, NHA and CTL. The HA group presented worse results for both unilateral
      and bilateral stance when compared with the other two cohorts. Surprisingly, the
      NHA group displayed a worse balance than the controls. A single calculated
      parameter (mean frequency) did not show significant differences. This apparently
      indicates the absence of pathology in the nervous system in relation to postural
      control. The results suggest that our patients should participate in physical
      exercise programmes, rehabilitation and physiotherapy to improve their postural
      control.

PMID- 18081833
TI  - Congenital FX deficiency combined with other clotting defects or with other
      abnormalities: a critical evaluation of the literature.
AB  - The presence of more than one congenital clotting defect in a given patient is a
      rare event but not an exceptional one. Combined defects of factor X (FX) are very
      rare because congenital isolated FX deficiency is by itself very rare. A perusal
      of personal files and of the literature has yielded 12 families with FX
      deficiency in which an association with another clotting factor deficiency was
      found. The associated defects were factor VII (FVII) or factor VIII (FVIII) or
      factor XII (FXII) deficiency. By far the most frequently associated was with
      FVII. Two forms of this association were found. In the first form there is casual
      association of both FVII and FX deficiency in the proband with independent
      recessive segregation of the two defects in other family members. The second form
      is because of abnormalities in chromosome 13 (deletions, translocations and so
      on) involving both FX and FVII genes. These genes are known to be very close and
      located on the long arm of chromosome 13 at about 13q34. In this form the
      hereditary pattern is autosomal dominant. Isolated FX deficiency and, more
      frequently, combined FX + FVII deficiency appear also associated with coagulation
      unrelated abnormalities (carotid body tumours, mitral valve prolapse, atrial
      septal defect, ventricular septal defect, thrombocytopenia absent radius (TAR)
      syndrome, mental retardation, microcephaly and cleft palate). Diagnosis of a
      combined clotting defect could be difficult on the basis of global tests. For
      example, both isolated FX deficiency and combined FX + FVII deficiency yield a
      prolongation of basal PTT and PT. Only specific assays could allow one to reach
      the correct diagnosis. In cases of casual association with other defects, it is
      also important to study family members, as the two defects should segregate
      independently.

PMID- 18081834
TI  - Single 270 microg kg(-1)-dose rFVIIa vs. standard 90 microg kg(-1)-dose rFVIIa
      and APCC for home treatment of joint bleeds in haemophilia patients with
      inhibitors: a randomized comparison.
AB  - Evidence suggests greater doses of recombinant activated factor VII (rFVIIa;
      NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) than currently administered may
      result in enhanced haemostasis and convenience for patients with haemophilia A
      and B with inhibitors. This study evaluated efficacy and safety of rFVIIa and an
      activated prothrombin complex concentrate (APCC; Factor Eight Inhibitor Bypassing
      Activity [FEIBA], Baxter AG, Vienna, Austria) for controlling joint bleeds in a
      home-treatment setting. Patients received each of three treatments in one of six
      possible sequences: 270 microg kg(-1) rFVIIa at hour 0 + placebo at hours 3 and
      6, 90 microg kg(-1) rFVIIa at hours 0, 3 and 6, and 75 U kg(-1) APCC at hour 0.
      Efficacy was assessed by the requirement for additional haemostatics within 9 h
      and by a novel global response algorithm. The percentage of rFVIIa 270 microg kg(
      1) group patients requiring additional haemostatics within 9 h (8.3%) was
      significantly lower than that for the APCC group (36.4%, P = 0.032). The
      percentage of rFVIIa 90 x 3 microg kg(-1) group patients requiring such rescue
      medication (9.1%) was also lower compared to the APCC group. This result
      approached, but did not reach statistical significance (P = 0.069). Both rFVIIa
      treatment groups showed similar use of rescue medication (8.3% and 9.1% of
      episodes for rFVIIa 270 microg kg(-1) and rFVIIa 90 x 3 microg kg(-1) groups
      respectively). No significant differences in treatment response were observed
      with the global response algorithm (P = 0.173). No safety issues were identified.
      A single dose of rFVIIa 270 microg kg(-1) is as safe and effective as rFVIIa 90 x
      3 microg kg(-1) dosing, and may be considered a potentially more effective
      alternative to APCCs for the management of joint bleeding in this population.

PMID- 18081835
TI  - Experimental animal use in the study of haemophilic bleeding.

PMID- 18081836
TI  - Immune tolerance induction with mycophenolate-mofetil in two children with
      haemophilia B and inhibitor.
AB  - Immune tolerance induction (ITI) in haemophilia B patients with inhibitor should
      be carefully considered because of the relatively poor (25%) overall success rate
      and the high risk of complications. ITI in combination with an immunosuppressive
      treatment was started in two children with haemophilia B with factor IX (FIX)
      inhibitor. To avoid anaphylactic reactions and inhibitor boost, the FIX
      replacement therapy was stopped and patients received a treatment with
      recombinant activated factor VII (rFVIIa). After disappearance of FIX inhibitor,
      a combination of mycophenolate-mofetil (MMF), dexamethasone (DEXA) and
      intravenous immunoglobulin (IVIG) and a high dose FIX replacement therapy was
      started. Immune tolerance could be induced in patient 2, whereas eradication of
      FIX inhibitor was incomplete in patient 1. Both patients benefited from the
      immune suppressive treatment and FIX replacement therapy was tolerated without
      any allergic complications. Neither development of a nephrotic syndrome nor a
      severe bleeding episode was observed. Strategies to induce tolerance in
      haemophilia B patients with inhibitors need to be explored in a systematic way.
      Given the low frequency of disease and even lower incidence of inhibitors,
      prospective randomized studies may not be possible. International registry-based
      retrospective and prospective data collection could play the key role in the
      study of the outcome variables in ITI for haemophilia B.

PMID- 18081837
TI  - Abnormal medial prefrontal cortex connectivity and defective fear extinction in
      the presymptomatic G93A SOD1 mouse model of ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal progressive neuropathy associated
      with the degeneration of spinal and brainstem motor neurons. Although ALS is
      essentially considered as a lower motor neuron disease, prefrontal cortex atrophy
      underlying executive function deficits have been extensively reported in ALS
      patients. Here, we examine whether prefrontal cortex neuronal abnormalities and
      related cognitive impairments are present in presymptomatic G93A Cu/Zn superoxide
      dismutase mice, a mouse model for familial ALS. Structural characteristics of
      prelimbic/infralimbic (PL/IL) medial prefrontal cortex (mPFC) neurons were
      studied in 3-month-old G93A and wild-type mice with the Golgi-Cox method, while
      mPFC-related cognitive operations were assessed using the conditioned fear
      extinction paradigm. Sholl analysis performed on the dendritic material showed a
      reduction in dendrite length and branch nodes on basal dendrites of PL/IL neurons
      in G93A mice. Spine density was also decreased on basal dendrite segments of
      branch order five. Consistent with the altered morphology of PL/IL cortical
      regions, G93A mice showed impaired extinction of conditioned fear. Our findings
      indicate that abnormal prefrontal cortex connectivity and function are
      appreciable before the onset of motor disturbances in this model.

PMID- 18081838
TI  - Complete mitochondrial genome sequence of the wine yeast Candida zemplinina:
      intraspecies distribution of a novel group-IIB1 intron with eubacterial
      affiliations.
AB  - The mtDNA of the ascomycetous wine yeast Candida zemplinina is a circularly
      mapping genome of 23,114 bp. It contains 35 genes coding for the seven basic
      subunits of oxidative phosporylation found in yeasts (the genes encoding for NADH
      oxidoreductase subunits are absent), the ribosomal protein Var1, two rRNAs and 25
      tRNA genes. Although protein phylogenetic analysis showed a divergent
      mitochondrial genome, several traits appeared preserved. The conserved gene
      blocks between the mtDNAs of C. zemplinina and Candida glabrata were maintained
      and changes in gene order and putative promoters were due to restricted genome
      reshuffling. New heterogeneous hairpin elements were identified scattered
      throughout cox1 introns. The large subunit rRNA gene harboured the first group
      IIB1 intron containing a putative active reverse transcriptase (RT) in
      mitochondrial genomes of fungi. Phylogenetic analysis of the RT protein confirmed
      its closer relationship to eubacterial intronic RTs, while being only distantly
      related to all other fungal mitochondrial group-II introns and RTs. The findings
      point towards an early migration event of a eubacterial group-II intron to the
      mitochondrial genome of C. zemplinina.

PMID- 18081839
TI  - The biosynthesis of peptidoglycan lipid-linked intermediates.
AB  - The biosynthesis of bacterial cell wall peptidoglycan is a complex process
      involving many different steps taking place in the cytoplasm (synthesis of the
      nucleotide precursors) and on the inner and outer sides of the cytoplasmic
      membrane (assembly and polymerization of the disaccharide-peptide monomer unit,
      respectively). This review summarizes the current knowledge on the membrane steps
      leading to the formation of the lipid II intermediate, i.e. the substrate of the
      polymerization reactions. It makes the point on past and recent data that have
      significantly contributed to the understanding of the biosynthesis of
      undecaprenyl phosphate, the carrier lipid required for the anchoring of the
      peptidoglycan hydrophilic units in the membrane, and to the characterization of
      the MraY and MurG enzymes which catalyze the successive transfers of the N
      acetylmuramoyl-peptide and N-acetylglucosamine moieties onto the carrier lipid,
      respectively. Enzyme inhibitors and antibacterial compounds interfering with
      these essential metabolic steps and interesting targets are presented.

PMID- 18081840
TI  - Diversity and distribution of hemerythrin-like proteins in prokaryotes.
AB  - Hemerythrins are oxygen-binding proteins found in the body fluids and tissues of
      certain invertebrates. Oxygen is bound at a nonheme iron centre consisting of two
      oxo-bridged iron atoms bound to a characteristic set of conserved histidine:
      aspartate and glutamate residues with the motifs H-HxxxE-HxxxH-HxxxxD. It has
      recently been demonstrated biochemically that two bacterial proteins bearing the
      same motifs do in fact possess similar iron centres and bind oxygen in the same
      way. The recent profusion of prokaryotic genomic sequence data has shown that
      proteins bearing hemerythrin motifs are present in a wide variety of bacteria,
      and a few archaea. Some of these are short proteins as in eukaryotes; others
      appear to consist of a hemerythrin domain fused to another domain, generally a
      putative signal transduction domain such as a methyl-accepting chemotaxis
      protein, a histidine kinase, or a GGDEF protein (cyclic di-GMP synthase). If, as
      initial evidence suggests, these are in fact hemerythrin-like oxygen-binding
      proteins, then their diversity in prokaryotes far exceeds that seen in
      eukaryotes. Here, a survey is presented of prokaryotic protein sequences bearing
      hemerythrin-like motifs, for which the designation 'bacteriohemerythrins' is
      proposed, and their functions are speculated.

PMID- 18081841
TI  - Microbial colonization of an in vitro model of a tissue engineered human skin
      equivalent--a novel approach.
AB  - This was a preliminary investigation to define the conditions of colonization of
      a human skin equivalent (SE) model with cutaneous microorganisms. SEs of 24 mm
      diameter were constructed with a dermal matrix of fibrin containing fibroblasts
      and a stratified epidermis. Microbial colonization of the SEs was carried out in
      a dry environment, comparable to 'in vivo' skin, using a blotting technique to
      remove inoculation fluid. The microbial communities were sampled by scrub washing
      and viable cells enumerated on selective growth medium. Staphylococcus
      epidermidis, Propionibacterium acnes and Malassezia furfur (human skin
      commensals) and Staphylococcus aureus (transient pathogen) were colonized at
      inoculum densities of 10(2)-10(6) CFU SE(-1) on the surface of replicate SEs.
      Growth of all species was supported for upto 72-120 h, with recovery densities of
      between 10(4)-10(9) CFU SE(-1). A novel, real-time growth monitoring method was
      also developed, using S. aureus containing a lux cassette. Light output increased
      from 20 to 95 h, and colonization increased from 10(2) to 10(8) CFU SE(-1), as
      confirmed by conventional recovery. Thus, the SE model has potential to
      investigate interactions between resident and transient microbial communities
      with themselves and their habitat, and for testing treatments to control pathogen
      colonization of human skin.

PMID- 18081843
TI  - Antibacterial activity of ZnO nanoparticle suspensions on a broad spectrum of
      microorganisms.
AB  - Nanoparticle metal oxides represent a new class of important materials that are
      increasingly being developed for use in research and health-related applications.
      Highly ionic metal oxides are interesting not only for their wide variety of
      physical and chemical properties but also for their antibacterial activity.
      Although the in vitro antibacterial activity and efficacy of regular zinc oxides
      have been investigated, little is known about the antibacterial activity of
      nanoparticles of ZnO. Preliminary growth analysis data suggest that nanoparticles
      of ZnO have significantly higher antibacterial effects on Staphylococcus aureus
      than do five other metal oxide nanoparticles. In addition, studies have clearly
      demonstrated that ZnO nanoparticles have a wide range of antibacterial effects on
      a number of other microorganisms. The antibacterial activity of ZnO may be
      dependent on the size and the presence of normal visible light. The data suggest
      that ZnO nanoparticles have a potential application as a bacteriostatic agent in
      visible light and may have future applications in the development of derivative
      agents to control the spread and infection of a variety of bacterial strains.

PMID- 18081842
TI  - Assimilation of homotaurine-nitrogen by Burkholderia sp. and excretion of
      sulfopropanoate.
AB  - Homotaurine (3-aminopropanesulfonate), free or derivatized, is in widespread
      pharmaceutical and laboratory use. Studies with enrichment cultures indicated
      that the compound is degradable as a sole source of carbon or as a sole source of
      nitrogen for bacterial growth. A pure culture of Burkholderia sp. was isolated
      which assimilated the amino group from homotaurine in a glucose-salts medium, and
      which released an organosulfonate, 3-sulfopropanoate, into the medium
      stoichiometrically. The deamination involved an inducible 2-oxoglutarate
      dependent aminotransferase to yield glutamate, and 3-sulfopropanal. Release of
      the amino group was attributed to the measured NADP-coupled glutamate
      dehydrogenase.

PMID- 18081844
TI  - Evidence that the potential for dissimilatory ferric iron reduction is widespread
      among acidophilic heterotrophic bacteria.
AB  - Nineteen characterized strains and isolates of acidophilic heterotrophic bacteria
      were screened for their abilities to catalyse the reductive dissolution of the
      ferric iron mineral schwertmannite, under oxygen-limiting conditions. Acidocella
      facilis, Acidobacterium capsulatum, and all of the Acidiphilium, Acidocella and
      Acidobacterium-like isolates that grew in liquid cultures were able to reduce
      iron. In contrast, neither Acidisphaera rubrifaciens nor three Acidisphaera-like
      isolates tested were found to have the capacity for dissimilatory iron reduction.
      One of two iron-oxidizing Frateuria-like isolates also reduced iron under oxygen
      limiting conditions. Microbial dissolution of schwertmannite was paralleled with
      increased concentrations of soluble ferrous iron and sulfate in microbial
      cultures, together with increased pH values and decreased redox potentials. While
      dissimilatory ferric iron reduction has been described previously for
      Acidiphilium spp., this is this first report of this capacity in Acidocella and
      the moderate acidophile Acidobacterium. The finding has significant implications
      for understanding of the biogeochemistry of acidic environments.

PMID- 18081845
TI  - A review on the interactions between gut microbiota and innate immunity of fish.
AB  - Although fish immunology has progressed in the last few years, the contribution
      of the normal endogenous microbiota to the overall health status has been so far
      underestimated. In this context, the establishment of a normal or protective
      microbiota constitutes a key component to maintain good health, through
      competitive exclusion mechanisms, and has implications for the development and
      maturation of the immune system. The normal microbiota influences the innate
      immune system, which is of vital importance for the disease resistance of fish
      and is divided into physical barriers, humoral and cellular components. Innate
      humoral parameters include antimicrobial peptides, lysozyme, complement
      components, transferrin, pentraxins, lectins, antiproteases and natural
      antibodies, whereas nonspecific cytotoxic cells and phagocytes
      (monocytes/macrophages and neutrophils) constitute innate cellular immune
      effectors. Cytokines are an integral component of the adaptive and innate immune
      response, particularly IL-1 beta, interferon, tumor necrosis factor-alpha,
      transforming growth factor-beta and several chemokines regulate innate immunity.
      This review covers the innate immune mechanisms of protection against pathogens,
      in relation with the installation and composition of the normal endogenous
      microbiota in fish and its role on health. Knowledge of such interaction may
      offer novel and useful means designing adequate therapeutic strategies for
      disease prevention and treatment.

PMID- 18081846
TI  - The role of monocyte/macrophages as vehicles of dissemination of Simkania
      negevensis: an in vitro simulation model.
AB  - Exposure to Simkania negevensis (Sn), an intracellular microorganism that has
      been associated with respiratory tract infections in infants and adults, is
      prevalent. Sn can multiply within free-living amoebae and has been detected in
      domestic water supplies, which may constitute a source of infection with the
      organism. Its path of transport from its portal of entry to the body to its
      target organs is unknown. In this study, the possibility that
      monocytes/macrophages may serve as vehicles of transmission was examined. In
      vitro cocultivation of Sn-infected Acanthamoeba polyphaga with the
      monocyte/macrophage cell line U937 resulted in the death of the amoebae and
      infection of the U937 cells. Sn entered and multiplied in U937 cells within short
      periods of time, and the microorganism could be transferred from U937 cells to
      cell cultures of various origins. Uninfected monocyte/macrophages could become
      infected when in contact with either actively or persistently Sn-infected cell
      cultures. Persistently infected cultures in contact with uninfected U937 cells
      became actively infected. The results of this study provide a basis for
      determination of the molecular mechanisms of monocyte/macrophage-cell
      interactions in transfer of infection and may contribute to a better
      understanding of the pathogenesis of Sn infections in vivo.

PMID- 18081847
TI  - Osteomyelitis and the role of biofilms in chronic infection.
AB  - Understanding the mechanisms implicated in the initial attachment, development,
      and maturation of a biofilm phenotype are of tremendous importance for their
      effect on the medical, industrial, and public health arenas. This review explores
      the current understanding of the nature of biofilms and the impact that molecular
      interactions between the bacteria themselves, as well as between bacteria and the
      host, may have on biofilm development and phenotype using the nonmotile Gram
      positive coccus, Staphylococcus aureus, as an example.

PMID- 18081848
TI  - T cell infiltration is associated with increased Lyme arthritis in TLR2-/- mice.
AB  - C57BL/6 mice deficient in TLR2 develop more severe arthritis following infection
      with Borrelia burgdorferi than do wild-type C57BL/6 mice, and this increase is
      suppressed by the simultaneous presence of the scid mutation. This suggested a
      requirement for lymphocytes in the development of subacute Lyme arthritis in
      TLR2(-/-) mice, a feature not commonly associated with this arthritis. The
      increased pathology of B. burgdorferi-infected TLR2(-/-) mice was also
      accompanied by an increase in mononuclear cell infiltration. In this study, T
      cells were found to be responsible for the increase in mononuclear cells in
      infected TLR2(-/-) C3H mice. Accordingly, transcripts for the IFN-inducible T
      cell chemokines, CXCL9 and CXCL10, were greatly enhanced in joint tissue from
      TLR2(-/-) mice, as were transcripts for a prototypical IFN-inducible gene IFN
      gamma-induced GTPase (igtp). Treatment of murine synovial cells with sonicated B.
      burgdorferi resulted in induction of transcripts for chemokines and other IFN
      inducible genes, irrespective of the presence of TLR2. The presence of T
      lymphocytes greatly enhanced the transcriptional response of synovial cells.
      These results suggest that the increased inflammatory cell infiltration in TLR2(
      /-) C3H mice is the result of localized overproduction of T cell attracting
      chemokines.

PMID- 18081849
TI  - Biological activities from extracts of endophytic fungi isolated from Viguiera
      arenaria and Tithonia diversifolia.
AB  - A total of 39 endophytic fungi have been isolated from Viguiera arenaria and
      Tithonia diversifolia, both collected in Sao Paulo State, Brazil. The isolates
      were identified based on their ribosomal DNA sequences. The ethyl acetate (EtOAc)
      extracts of all endophytic fungi were evaluated for their antimicrobial,
      antiparasitic and antitumoral activity. Antimicrobial screening was conducted
      using an agar diffusion assay against three pathogenic microorganisms:
      Staphylococcus aureus, Escherichia coli and Candida albicans. Antiparasitic
      activity was determined by enzymatic inhibition of gGAPDH of Trypanosoma cruzi
      and adenine phosphorybosiltransferase (APRT) of Leishmania tarentolae.
      Antitumoral activity was tested against human T leukemia cells by the Mosmann
      colorimetric method. All extracts showed activity in at least one assay: 79.5% of
      the extracts were cytotoxic against leukemia cells, 5.1% of the extracts were
      active against S. aureus, 25.6% against E. coli and 64.1% against Candida
      albicans. Only one extract showed promising results in the inhibition of
      parasitic enzymes gGAPDH (95.0%) and three were found to inhibit APRT activity.
      The cytotoxic extract produced by the strain VA1 (Glomerella cingulata) was
      fractionated and yielded nectriapyrone and tyrosol. Nectriapyrone showed relevant
      cytotoxic activity against both human T leukemia and melanoma tumor cell lines.

PMID- 18081850
TI  - M-cells: origin, morphology and role in mucosal immunity and microbial
      pathogenesis.
AB  - M-cells are specialized cells found in the follicle-associated epithelium of
      intestinal Peyer's patches of gut-associated lymphoid tissue and in isolated
      lymphoid follicles, appendix and in mucosal-associated lymphoid tissue sites
      outside the gastrointestinal tract. In the gastrointestinal tract, M-cells play
      an important role in transport of antigen from the lumen of the small intestine
      to mucosal lymphoid tissues, where processing and initiation of immune responses
      occur. Thus, M-cells act as gateways to the mucosal immune system and this
      function has been exploited by many invading pathogens. Understanding the
      mechanism by which M-cells sample antigen will inform the design of oral vaccines
      with improved efficacy in priming mucosal and systemic immune responses. In this
      review, the origin and morphology of M-cells, and their role in mucosal immunity
      and pathogenesis of infections are discussed.

PMID- 18081851
TI  - Pro-inflammatory cytokine release in keratinocytes is mediated through the MAPK
      signal-integrating kinases.
AB  - The mitogen-activated protein kinases (MAPKs) are known to play a key role in the
      regulation of cytokine expression in several cell types. MAPK signal-integrating
      kinase 1 (Mnk1) is a kinase activated through both the stress- and cytokine
      activated p38 MAPK pathway and the classical extracellular signal-regulated
      kinase 1/2 (ERK1/2) pathway. In this study, we demonstrate that in cultured
      normal human keratinocytes Mnk1 and its downstream target eukaryotic initiation
      factor 4E (eIF4E) are phosphorylated in a time-dependent manner in response to
      stimulation with anisomycin or interleukin (IL)-1beta. Both the stimuli are well
      recognized activators of the p38 MAPK pathway. Furthermore, we show that the Mnk
      inhibitor CGP57380 is capable of inhibiting the phosphorylation of eIF4E in
      keratinocytes, and that the abolishment of eIF4E phosphorylation dramatically
      decreases the anisomycin-induced protein release of the pro-inflammatory
      cytokines tumor necrosis factor-alpha (TNF-alpha), IL-1beta and IL-6 as well as
      the IL-1beta-induced protein release of TNF-alpha. Therefore, we propose that
      Mnk1 might contribute to the expression of pro-inflammatory cytokines found in
      inflammatory skin diseases.

PMID- 18081852
TI  - CD40 ligation during dendritic cell maturation reduces cell death and prevents
      interleukin-10-induced regression to macrophage-like monocytes.
AB  - Dendritic cells (DCs) have become popular candidates in cancer vaccination
      because of their crucial role in inducing T-cell responses. However, clinical
      studies greatly differ in their protocols for generating DCs and the efficacy in
      treating established tumors needs to be improved. We systematically analyzed DCs
      maturated by five different protocols for surface markers, the alloproliferative
      T-cell response, the DC survival after cytokine deprivation, the stability of
      surface markers under the influence of interleukin-10 (IL-10) and the DC cytokine
      secretion pattern. Monocyte-derived DCs were maturated by CD40-ligand (CD40-L),
      unmethylated cytosine-guanosine dinucleotides-oligodinucleotides (CpG-ODN), an
      inflammatory cytokine cocktail (ICC), a combination of ICC and CD40-L, or ICC,
      CD40-L and CpG-ODN. A high co-expression of DC maturation and costimulation
      markers was found after treatment with ICC plus CD40-L (69.3 +/- 9.6% CD83/CD80
      double positive staining) and correlated with a significantly increased cell
      survival, a high expression of the antiapoptotic factor bcl-(XL), a stable
      CD83(high)/CD14(low) expression under the influence of IL-10, and a strong
      alloproliferative T-cell response. In conclusion, our data support the use of
      maturation protocols containing ICC plus CD40-L in order to generate highly
      mature, phenotypically stable, cell-death resistant, and T-cell stimulatory DCs
      for clinical application in cancer patients.

PMID- 18081853
TI  - Global features of the Alcanivorax borkumensis SK2 genome.
AB  - The global feature of the completely sequenced Alcanivorax borkumensis SK2 type
      strain chromosome is its symmetry and homogeneity. The origin and terminus of
      replication are located opposite to each other in the chromosome and are
      discerned with high signal to noise ratios by maximal oligonucleotide usage
      biases on the leading and lagging strand. Genomic DNA structure is rather uniform
      throughout the chromosome with respect to intrinsic curvature, position
      preference or base stacking energy. The orthologs and paralogs of A. borkumensis
      genes with the highest sequence homology were found in most cases among gamma
      Proteobacteria, with Acinetobacter and P. aeruginosa as closest relatives. A.
      borkumensis shares a similar oligonucleotide usage and promoter structure with
      the Pseudomonadales. A comparatively low number of only 18 genome islands with
      atypical oligonucleotide usage was detected in the A. borkumensis chromosome. The
      gene clusters that confer the assimilation of aliphatic hydrocarbons, are
      localized in two genome islands which were probably acquired from an ancestor of
      the Yersinia lineage, whereas the alk genes of Pseudomonas putida still exhibit
      the typical Alcanivorax oligonucleotide signature indicating a complex evolution
      of this major hydrocarbonoclastic trait.

PMID- 18081854
TI  - Relationship between assemblages of mycorrhizal fungi and bacteria on grass
      roots.
AB  - Soils support an enormous microbial diversity, but the ecological drivers of this
      diversity are poorly understood. Interactions between the roots of individual
      grass species and the arbuscular mycorrhizal (AM) fungi and bacteria in their
      rhizoplane were studied in a grazed, unimproved upland pasture. Individual root
      fragments were isolated from soil cores, DNA extracted and used to identify plant
      species and assess rhizoplane bacterial and AM fungal assemblages, by amplifying
      part of the small-subunit ribosomal RNA gene, followed by terminal restriction
      fragment length polymorphism analysis. For the first time we showed that AM
      fungal and bacterial assemblages are related in situ and that this relationship
      occurred at the community level. Principal coordinate analyses of the data show
      that the AM fungi were a major factor determining the bacterial assemblage on
      grass roots. We also report a strong influence of the composition of the plant
      community on AM fungal assemblage. The bacterial assemblage was also influenced
      by soil pH and was spatially structured, whereas AM fungi were influenced neither
      by the bacteria nor by soil pH. Our study shows that linkages between plant roots
      and their microbial communities exist in a complex web of interactions that act
      at individual and at community levels, with AM fungi influencing the bacterial
      assemblage, but not the other way round.

PMID- 18081855
TI  - An investigation into the effect of potassium ions on the folding of silk fibroin
      studied by generalized two-dimensional NMR-NMR correlation and Raman
      spectroscopy.
AB  - We used generalized two-dimensional NMR-NMR correlation to examine the effect of
      potassium ions on the conformation transition in silk fibroin to investigate the
      possibility that the fairly high K+ ion content found in the distal end of silk
      secreting ducts in the silkworms could have a bearing on natural formation of the
      silk fiber. This has enabled us to propose a detailed mechanism for the
      transition process. Our evidence indicates that increasing the [K+] from 0 to 3.7
      mg.g(-1) in the silk fibroin, as is thought to occur as the silk fibroin moves
      through the secretory pathway to the spigot, produces a sequence of secondary
      structural changes: helix and/or random coil-->helix-like-->beta-sheet-like-
      >beta-sheet. The sequence is the same as that produced in silk fibroin films by
      decreasing the pH of fibroin from 6.8 to 4.8. In addition, we used Raman
      spectroscopy to study the effect of K+ ions on the Fermi doublet resonance of the
      tyrosyl phenolic ring at 850 and 830 cm(-1). The intensity ratio I(850)/I(830) at
      these wave numbers indicated that the hydrogen bonding formed by the tyrosyl
      phenolic-OH becomes more stable with an increase in the K+ ion concentration as
      above. Our investigation on the effect of K+ ions on fibroin may help provide a
      theoretical basis for understanding the natural silk-spinning process and the
      conditions required for biomimetic spinning. It may also have relevance to the
      aggregation of other beta-sheet proteins, including prion proteins,
      neurofibrillary proteins and amyloid plaques.

PMID- 18081856
TI  - Atypical Microsporum canis variant in an immunosuppressed child.
AB  - A 10-year old boy with X-chromosomal adrenoleukodystrophy presented with scaly
      patches on the scalp and diffuse effluvium. He was on immunosuppressive therapy
      because of a chronic graft-versus-host-reaction after allogenic bone marrow
      transplantation. At home he had been in contact with cats, rabbits and guinea
      pigs. Through Wood light and KOH examination, we confirmed the diagnosis of tinea
      capitis and started antimycotic therapy. The morphology of the culture first
      suggested Epidermophyton floccosum, Trichophyton mentagrophytes var. nodulare or
      Trichophyton tonsurans as possible causes for this infection. Further studies,
      however, revealed an atypical form of Microsporum canis infection.

PMID- 18081857
TI  - Injection lipolysis for reduction of saddlebag trochanteric bulges--half-side
      controlled pilot study.
AB  - BACKGROUND: Phosphatidylcholine, a lecithin extracted from soybeans can reduce
      serum cholesterol to some extent. Intravenous use may prevent fat embolism in
      polytrauma patients. When injected intralesionally in a formulation containing
      also deoxycholate and ethanol it is supposed to act as "fat burner" to reduce
      undesired fat deposits; there is little evidence-based scientific support for
      this indication. OBJECTIVE: To evaluate the capability of phosphatidylcholine +
      deoxycholate + ethanol (PPC/DC/E) to reduce body fat with a half-side pilot study
      for the reduction of saddlebag trochanteric bulges. METHODS: PPC/DC/E was
      injected into the right posterior trochanteric areas three times at weeks 0, 3
      and 6. Treatment areas and the same regions of the contralateral side as a
      control were evaluated by sonography. Tape measurements were taken and the
      thickness of the subcutaneous adipose tissue (SAT) was measured with an optical
      device (Lipometer) at baseline and at week 8 and week 20 (2 and 14 weeks after
      completing therapy). RESULTS: In this half-side trial, no significant reduction
      of subcutaneous fat was achieved after three treatments with PPC/DC/E when
      compared to the untreated side.Transient inflammatory reactions occurred in all
      patients. LIMITATIONS: Only the commercially available formulation containing the
      three components was tested. CONCLUSION: The off-label use of PPC/DC/E as a "fat
      burner" did not produce measurable reduction of undesired trochanteric fat
      deposits.

PMID- 18081858
TI  - C-reactive protein associated with periodontitis in a Thai population.
AB  - AIM: C-reactive protein (CRP) has been implicated as a possible mediator of the
      association between periodontitis and several systemic diseases. Previous studies
      suggest an association between increased CRP levels and periodontitis
      predominantly in Caucasians. This study evaluated the associations of chronic
      periodontitis and Porphyromonas gingivalis with CRP in systemically healthy Thai
      adults. MATERIAL AND METHODS: Serum high-sensitivity CRP was measured in 21
      generalized periodontitis, 62 localized periodontitis, and 38 periodontally
      healthy control subjects. P. gingivalis in subgingival plaque samples was
      analyzed by polymerase chain reaction. RESULTS: Overall, these subjects had a
      median CRP level lower than that reported in the western populations. Subjects
      with generalized periodontitis and localized periodontitis had higher median CRP
      levels than controls (1.78 and 0.65 mg/l versus 0.25 mg/l, p<0.001). Multivariate
      linear regression showed that log CRP levels were increased in subjects with
      generalized periodontitis (p<0.01) and localized periodontitis (p=0.03) compared
      with the controls, adjusted for age, body mass index and smoking. Presence of P.
      gingivalis was also independently associated with elevated log CRP levels
      (p<0.001). CONCLUSION: Periodontitis and subgingival P. gingivalis are associated
      with increased CRP levels. These findings suggest that periodontal infection may
      contribute to systemic inflammatory burden in otherwise healthy individuals.

PMID- 18081859
TI  - Enamel matrix derivative and low-level laser therapy in the treatment of intra
      bony defects: a randomized placebo-controlled clinical trial.
AB  - AIM: The aim of this study was to evaluate the immediate post-operative pain,
      wound healing and clinical results after the application of an enamel matrix
      protein derivative (EMD) alone or combined with a low-level laser therapy (LLLT)
      for the treatment of deep intra-bony defects. MATERIAL AND METHODS: This study
      was an intra-individual longitudinal test of 12 months' duration conducted using
      a blinded, split-mouth, placebo-controlled and randomized design. In 22
      periodontitis patients, one intra-bony defect was randomly treated with EMD+LLLT,
      while EMD alone was applied to the contra-lateral defect site. LLLT was used both
      intra- and post-operatively. Clinical measurements were performed by a blinded
      periodontist at the time of surgery, in the first week and in the first, second,
      sixth and 12th month. Visual analogue scale (VAS) scores were recorded for pain
      assessment. RESULTS: The results have shown that the treatment of intra-bony
      defects with EMD alone or EMD+LLLT leads to probing depth reduction and
      attachment-level gain. In addition, EMD+LLLT had resulted in less gingival
      recession (p<0.05), less swelling (p<0.001) and less VAS scores (p<0.02) compared
      with EMD alone. CONCLUSION: This study shows that EMD is an effective, safe and
      predictable biomaterial for periodontal regeneration and LLLT may improve the
      effects of EMD by reducing post-operative complications.

PMID- 18081860
TI  - Self-reported gingivitis and tooth loss poorly predict C-reactive protein levels:
      a study among Finnish young adults.
AB  - OBJECTIVES: Our aim in this cross-sectional study was to investigate whether self
      reported gingivitis and tooth loss were associated with elevated levels of C
      reactive protein (CRP) using the same study population where these dental
      conditions have earlier been associated with prevalent angina pectoris. MATERIAL
      AND METHODS: The study population consisted of those Northern Finland birth
      cohort 1966 members who lived in Northern Finland or in the Helsinki region
      (n=8463) at the time of the survey (1996-1997). The participation rate in a
      health examination was 71% (n=6033). Gingivitis and tooth loss were determined on
      the basis of self-reported questions. Prevalence proportion ratios (PPR) and 95%
      confidence intervals (CI) were estimated using multivariate regression models.
      RESULTS: The results showed that self-reported gingivitis and tooth loss were
      weakly associated with elevated levels of CRP (>3 mg/l): adjusted PPR 1.1, CI 1.0
      1.3 and PPR 1.1, CI 0.7-1.7, respectively. The proportion of variation in CRP
      explained by self-reported gingivitis and tooth loss was small, being <1%.
      CONCLUSION: The results suggest that self-reported gingivitis and tooth loss have
      a miniscule effect on CRP levels among a general population of young adults.

PMID- 18081861
TI  - Is there a temporal trend in the reported treatment efficacy of periodontal
      regeneration? A meta-analysis of randomized-controlled trials.
AB  - BACKGROUND/AIM: The aim of study was to conduct a meta-analysis to investigate
      whether or not there was a temporal trend in the treatment efficacy reported in
      the randomized-controlled trials (RCTs) on guided tissue regeneration (GTR) or
      enamel matrix protein derivatives (EMD) in the treatment of infrabony defects.
      MATERIAL AND METHODS: The treatment outcomes were changes in probing pocket depth
      (PPD) and clinical attachment level (CAL). Weighted multilevel and ordinary
      regression analyses were performed to test the temporal relationship between
      treatment effect difference or treatment effectiveness and publication years.
      RESULTS: For PPD reduction, non-significant positive relationships were found in
      the treatment effect difference or treatment effect of both GTR and flap
      operation. For CAL gain, a small positive relationship was found in the treatment
      effect difference, but a significant positive trend in the treatment effect of
      flap operation was found. No significant temporal trend was found in the
      treatment effect difference for EMD. CONCLUSIONS: There was no evidence to
      support or refute a temporal trend in the treatment effect of regenerative
      procedures, but a positive trend was observed in the control group. These results
      suggest that only RCTs should be included in the meta-analysis, as the treatment
      effect of the control group may not be constant.

PMID- 18081862
TI  - Subgingival microbial profiles in chronic periodontitis patients from Chile,
      Colombia and Spain.
AB  - AIM: To investigate the subgingival microbiota of distinct periodontitis patient
      populations, in Chile, Colombia and Spain, using identical clinical and
      bacteriological methods. MATERIAL AND METHODS: In this multicentre study, 114
      chronic periodontitis patients were selected. Patients were examined using an
      identical clinical protocol and pooled subgingival samples were obtained from
      each patient. Samples were processed in the three laboratories by means of
      culturing under identical clinical and microbiological protocols. Total anaerobic
      counts and frequency of detection and proportions of nine periodontal pathogens
      were calculated. Variables were analysed by means of anova, chi(2), Kruskal
      Wallis and Dunn's multiple comparison tests. RESULTS: The Colombian population
      demonstrated greater severity of periodontitis, with significantly deeper mean
      probing pocket depth, and had a significantly lower percentage of current
      smokers. When comparing samples from the three patient populations, the total
      counts were significantly higher in the Colombian patients. The numbers of
      putative pathogens differed among groups. Tannerella forsythia was found less
      frequently in Chilean samples, while Parvimonas micra and enteric rods differed
      significantly among the three population groups. CONCLUSION: Significant
      differences among Chile, Colombia and Spain existed regarding the frequency and
      proportions of specific periodontal pathogens in the subgingival microbiota of
      periodontitis patients.

PMID- 18081863
TI  - Dual P2Y 12 receptor signaling in thrombin-stimulated platelets--involvement of
      phosphoinositide 3-kinase beta but not gamma isoform in Ca2+ mobilization and
      procoagulant activity.
AB  - During thrombus formation, thrombin, which is abundantly present at sites of
      vascular injury, activates platelets in part via autocrine-produced ADP. We
      investigated the signaling pathways by which thrombin and ADP in synergy induced
      platelet Ca(2+) elevation and procoagulant activity, and we monitored the
      consequences for the coagulation process. Even at high thrombin concentration,
      autocrine and added ADP enhanced and prolonged Ca(2+) depletion from internal
      stores via stimulation of the P2Y(12) receptors. This P2Y(12)-dependent effect
      was mediated via two distinct signaling pathways. The first is enhanced Ca(2+)
      mobilization by the inositol 1,4,5-trisphosphate receptors due to inhibition of
      protein kinase A. The second pathway concerns prolonged activation of
      phosphoinositide 3-kinase (PI3-K) and phospholipase C. Experiments with
      phosphoinositide 3-kinase isoform-selective inhibitors and p110gamma deficient
      platelets demonstrated that the phosphoinositide 3-kinase beta and not the
      phosphoinositide 3-kinase gamma isoform is responsible for the prolonged Ca(2+)
      response and for the subsequent increases in procoagulant activity and
      coagulation. Taken together, these results demonstrate a dual P2Y(12)-dependent
      signaling mechanism, which increases the platelet-activating effect of thrombin
      by prolongation of Ca(2+) elevation, thereby facilitating the coagulation
      process.

PMID- 18081864
TI  - Poly(silicate)-metabolizing silicatein in siliceous spicules and silicasomes of
      demosponges comprises dual enzymatic activities (silica polymerase and silica
      esterase).
AB  - Siliceous sponges can synthesize poly(silicate) for their spicules enzymatically
      using silicatein. We found that silicatein exists in silica-filled cell
      organelles (silicasomes) that transport the enzyme to the spicules. We show for
      the first time that recombinant silicatein acts as a silica polymerase and also
      as a silica esterase. The enzymatic polymerization/polycondensation of silicic
      acid follows a distinct course. In addition, we show that silicatein cleaves the
      ester-like bond in bis(p-aminophenoxy)-dimethylsilane. Enzymatic parameters for
      silica esterase activity are given. The reaction is completely blocked by sodium
      hexafluorosilicate and E-64. We consider that the dual function of silicatein
      (silica polymerase and silica esterase) will be useful for the rational synthesis
      of structured new silica biomaterials.

PMID- 18081865
TI  - Ciz1, a p21 cip1/Waf1-interacting zinc finger protein and DNA replication factor,
      is a novel molecular partner for human enhancer of rudimentary homolog.
AB  - Enhancer of rudimentary homolog (Drosophila) (ERH) is a small, highly conserved,
      nuclear protein with a unique three-dimensional structure, whose gene has been
      identified in animals, plants and protists, but not in fungi. Involvement of ERH
      in fundamental processes such as regulation of pyrimidine metabolism, cell cycle
      progression, transcription and cell growth control has been suggested. Here,
      employing a yeast two-hybrid system, a glutathione S-transferase pull-down assay
      and tandem MS, we demonstrate that Ciz1 is a bona fide interactor of human ERH.
      Ciz1 is a nuclear zinc finger protein interacting with p21(Cip1/Waf1), a
      universal inhibitor of cyclin-dependent kinases, and is a DNA replication factor.
      The region of Ciz1 necessary for the interaction with ERH spans residues 531-644,
      encompassing its first zinc finger motif. This region overlaps the p21(Cip1/Waf1)
      binding site, suggesting that the interaction with ERH could block the binding of
      p21(Cip1/Waf1) by Ciz1 in the cell. When ERH and Ciz1 are coexpressed in HeLa
      cells, Ciz1 recruits ERH to DNA replication foci.

PMID- 18081866
TI  - Mammalian Gup1, a homolog of Saccharomyces cerevisiae glycerol uptake/transporter
      1, acts as a negative regulator for N-terminal palmitoylation of Sonic hedgehog.
AB  - Mammalian glycerol uptake/transporter 1 (Gup1), a homolog of Saccharomyces
      cerevisiae Gup1, is predicted to be a member of the membrane-bound O
      acyltransferase family and is highly homologous to mammalian hedgehog
      acyltransferase, known as Skn, the homolog of the Drosophila skinny hedgehog gene
      product. Although mammalian Gup1 has a sequence conserved among the membrane
      bound O-acyltransferase family, the histidine residue in the motif that is
      indispensable to the acyltransferase activity of the family has been replaced
      with leucine. In this study, we cloned Gup1 cDNA from adult mouse lung and
      examined whether Gup1 is involved in the regulation of N-terminal palmitoylation
      of Sonic hedgehog (Shh). Subcellular localization of mouse Gup1 was
      indistinguishable from that of mouse Skn detected using the fluorescence of
      enhanced green fluorescent protein that was fused to each C terminus of these
      proteins. Gup1 and Skn were co-localized with an endoplasmic reticulum marker, 78
      kDa glucose-regulated protein, suggesting that these two molecules interact with
      overlapped targets, including Shh. In fact, full-length Shh coprecipitated with
      FLAG-tagged Gup1 by immunoprecipitation using anti-FLAG IgG. Ectopic expression
      of Gup1 with full-length Shh in cells lacking endogenous Skn showed no hedgehog
      acyltransferase activity as determined using the monoclonal antibody 5E1, which
      was found to recognize the palmitoylated N-terminal signaling domain of Shh under
      denaturing conditions. On the other hand, Gup1 interfered with the palmitoylation
      of Shh catalyzed by endogenous Skn in COS7 and NSC34. These results suggest that
      Gup1 is a negative regulator of N-terminal palmitoylation of Shh and may
      contribute to the variety of biological actions of Shh.

PMID- 18081867
TI  - Surgical factors influencing mesiodistal implant angulation.
AB  - OBJECTIVES: The aim of this experimental study was to identify relevant surgical
      parameters influencing the mesiodistal angular deviation of dental implants.
      MATERIAL AND METHODS: Pilot drillings of 2 mm diameter were performed in bovine
      ribs with a parallelometer. The subsequent preparation of the implant socket was
      performed freehand. Utilizing six different implant systems, at least 80
      drillings per system of different diameters were performed. The pilot drillings
      were marked with 2 mm steel pins and cephalometric radiographs were taken. The
      mesiodistal angle between the longitudinal implant axis and the marked pilot
      drillings was measured and evaluated by a blinded investigator. To evaluate the
      influence of the surgeons' experience, their drillings were compared with those
      of a group of unexperienced surgeons. Additionally, the influence of drilling
      speed and size of bur steps on drilling accuracy were evaluated. RESULTS: The
      difference between the lowest value of 0.91 degrees of mesiodistal angular
      deviation found for 3i implants and the highest of 1.36 degrees for Ankylos
      implants was of low statistical significance (P=0.065). Drillings of experienced
      surgeons showed less deviation compared with those of a beginners group
      (P<0.0001). Higher deviations were measured when a bur size was skipped.
      Drillings performed at high speed showed significantly higher deviations than
      those with fewer rewinds per minute. CONCLUSION: In order to achieve precise
      implant angulation, all bur diameters available should be used. Utilizing low
      drilling speeds results in less mesiodistal deviation. The surgeon's experience
      seems to be the most relevant factor in precise implant placement.

PMID- 18081868
TI  - Osteoprotegerin levels in peri-implant crevicular fluid.
AB  - AIMS: To evaluate the levels of soluble receptor activator of nuclear factor
      kappaB ligand (sRANKL) and osteoprotegerin (OPG) in crevicular fluid of
      endosseous dental implants. METHODS: Eighty-six implants in 39 patients were
      evaluated. All patients were treated with root-type implants placed at least 16
      months and loaded at least 12 months before the examination. Peri-implant
      crevicular fluid (PICF) samples were obtained from buccal and lingual aspects of
      implants. Modified plaque index, probing depth, gingival index, and bleeding on
      probing (BOP) were recorded at four sites per implant. PICF levels of sRANKL and
      OPG were analysed by ELISA. Spearman's correlations were utilised to relate
      biochemical data and clinical parameters. RESULTS: The PICF level of sRANKL did
      not show significant correlation with the clinical parameters or the OPG level.
      The total amount of OPG was positively correlated with PICF volume, gingival
      index, and BOP (P<0.05) and negatively correlated with pack years (P<0.05).
      CONCLUSION: The findings of this preliminary study suggest that the crevicular
      fluid level of OPG deserves further investigation as a possible marker to
      evaluate the health status of surrounding tissues of dental implants, as this was
      not the case for the sRANKL level. Larger scale studies, particularly in peri
      implantitis cases, may shed more light on this subject.

PMID- 18081869
TI  - Bone regeneration of dental implant dehiscence defects using a cultured
      periosteum membrane.
AB  - OBJECTIVES: This study aimed to demonstrate the feasibility of a cultured
      periosteum (CP) membrane for use in guided bone regeneration at sites of implant
      dehiscence. MATERIAL AND METHODS: Four healthy beagle dogs were used in this
      study. Implant dehiscence defects (4 x 4 x 3 mm) were surgically created at
      mandibular premolar sites where premolars had been extracted 3 months back.
      Dental implants (3.75 mm in diameter and 7 mm in length) with machined surfaces
      were placed into the defect sites (14 implants in total). Each dehiscence
      defective implant was randomly assigned to one of the following two groups: (1)
      PRP gel without cells (control) or (2) a periosteum membrane cultured on PRP gel
      (experimental). Dogs were killed 12 weeks after operation and nondecalcified
      histological sections were made for histomorphometric analyses including percent
      linear bone fill (LF) and bone-to-implant contact (BIC). RESULTS: Bone
      regeneration in the treatment group with a CP membrane was significantly greater
      than that in the control group and was confirmed by LF analysis. LF values in the
      experimental and the control groups were 72.36+/-3.14% and 37.03+/-4.63%,
      respectively (P<0.05). The BIC values in both groups were not significantly
      different from each other. The BIC values in the experimental and the control
      groups were 40.76+/-10.30% and 30.58+/-9.69%, respectively (P=0.25) and were
      similar to native bone. CONCLUSION: This study demonstrated the feasibility of a
      CP membrane to regenerate bone at implant dehiscence defect.

PMID- 18081870
TI  - Immediately loaded titanium implant with a tissue-stabilizing/maintaining design
      ('beyond platform switch') retrieved from man after 4 weeks: a histological and
      histomorphometrical evaluation. A case report.
AB  - BACKGROUND: After implant insertion and loading, crestal bone usually undergoes
      remodeling and resorption. If the horizontal relationship between the outer edge
      of the implant and a smaller-diameter component ('platform switching') is
      altered, there seems to be reduced crestal bone loss. Immediate loading allows
      immediate restoration of esthetics and function, reduces morbidity, and
      facilitates functional rehabilitation. MATERIALS AND METHODS: Three Morse cone
      connection implants were inserted in the right posterior mandible in a 29-year
      old partially edentulous patient. The platform of the implant was inserted 2 mm
      below the level of the alveolar crest. After a 1-month loading period, the most
      distal mandibular implant was retrieved with a trephine bur for psychological
      reasons. RESULTS: At low-power magnification, it was possible to see that bone
      was present 2 mm above the level of the implant shoulder. No resorption of the
      coronal bone was present. No infrabony pockets were present. At the level of the
      shoulder of the implant, it was possible to observe the presence of dense
      connective tissue with only a few scattered inflammatory cells. Newly formed bone
      was found in direct contact with the implant surface. The bone-implant contact
      percentage was 65.3+/-4.8%. CONCLUSIONS: Abutments smaller than the diameter of
      the implant body (platform switching) in combination with an absence of
      micromovement and microgap may protect the peri-implant soft and mineralized
      tissues, explaining the observed absence of bone resorption. Immediate loading
      did not interfere with bone formation and did not have adverse effects on
      osseointegration.

PMID- 18081871
TI  - Step-wise analysis of the dental implant insertion process using the finite
      element technique.
AB  - OBJECTIVES: Using the finite element method (FEM), the insertion process of a
      dental implant into a section of the human mandible is analysed. The ultimate aim
      of this article is to advance the use of an innovative engineering approach in
      dental practices, especially in the process of dental implantation. MATERIAL AND
      METHODS: The FEM and analysis techniques are used to replicate and evaluate the
      stress profile created within the mandible during the implantation process.
      RESULTS: The von Mises stress profiles in both cancellous and cortical bone are
      examined during implant insertion. The applied torque and the insertion stage are
      found to strongly influence the resulting stress profile within the surrounding
      jawbone. CONCLUSIONS: Through the combination of both dental and engineering
      expertise, a simplified and efficient modelling technique is developed. This
      improves the understanding of the biomechanical reaction that the jawbone
      exhibits due to the insertion of implant. The current research is a pilot study
      using the FEM to model and simulate the dental implantation process. The
      assumptions made in the modelling and simulation process are: (1) the
      implantation process is simulated as a step-wise process instead of a continuous
      process; (2) the implant is parallel threaded and the implant does not rotate
      during insertion into the jawbone. Although the modelling and simulation
      techniques had to be simplified, a significant amount of information is gained
      that helps lay a good foundation for future research. Recommendations for future
      studies include the variation of the torque applied during the implantation
      process and upgrading the software capabilities to simulate the full dynamical
      process of implantation.

PMID- 18081872
TI  - Biomechanical rationale for a single implant-retained mandibular overdenture: an
      in vitro study.
AB  - OBJECTIVES: This study aimed to examine the biomechanical rationale of a single
      implant-retained overdenture (SIO) system using an in vitro model. MATERIAL AND
      METHODS: Laboratory implant analogs (3.75 x 13 mm) were embedded into the midline
      and canine regions on both sides of the mandibular phantom model with artificial
      mucosa. Magnetic attachments (flat, FM; dome, DM) and a ball attachment (Ball)
      were mounted to the abutment where lateral forces were measured with four
      miniature strain gauges attached to the surface. A 50 N static load was applied
      at five different sites of the occlusal surface of the simulated denture base
      using each counterpart of the attachments. Strain data were compared between SIO
      and two implant-retained configurations (TIO) with three attachments. Three
      dimensional (3D) denture base displacements were also measured. Statistical
      analysis was performed by multiple comparisons using a post hoc test (P<0.05).
      RESULTS: Statistically significantly smaller lateral forces to abutments were
      obtained in SIO than in TIO with the Ball with the molar load, while there were
      no statistical differences between SIO and TIO with FM. There were no statistical
      differences in 3D denture base movements between SIO and TIO in the midline and
      molar regions, while there were larger movements in SIO than in TIO with FM.
      CONCLUSION: Within the limitations of our in vitro study, we suggested that
      single-implant overdentures with dome-type magnet or ball attachments had
      biomechanical effects similar to two-implant overdentures in terms of lateral
      forces to the abutment and denture base movements under molar functional loads.

PMID- 18081874
TI  - Serum macrophage migration inhibitory factor (MIF) levels after allogeneic
      hematopoietic stem cell transplantation.
AB  - Macrophage migration inhibitory factor (MIF) may play an important role in the
      pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic
      hematopoietic stem cell transplantation (allo-HSCT), as MIF plays an important
      role to regulate the production of tumor necrosis factor-alpha (TNF-alpha), one
      of the inflammatory cytokines which induces and exacerbates aGVHD. We examined
      the association between serum MIF levels and aGVHD vs. chronic GVHD (cGVHD) in
      allo-SCT patients in this study. We found a significant increase in the peak
      serum MIF (14.46 ng +/- 1.47 ng/ml) at onset in patients that developed aGVHD (n
      = 23, P = 0.009). We also found that mean serum MIF levels in patients who
      developed extensive type cGVHD within 6 months (12.58 +/- 2.18 ng/ml, n = 13)
      were significantly higher than MIF levels before allo-HSCT (7.86 +/- 1.17 ng/ml,
      n = 19, P = 0.04). Therefore, we speculated that serum MIF levels increase during
      the active phase of both aGVHD and cGVHD.

PMID- 18081876
TI  - Downregulation of ING3 mRNA expression predicts poor prognosis in head and neck
      cancer.
AB  - Although many clinical and pathological prognostic factors such as tumor stage
      and lymph-node involvement have been described, to date no reliable or clinically
      applicable marker or tumor aggressiveness has been identified for head and neck
      cancer. In an attempt to identify such a molecular prognostic marker, we analyzed
      the mRNA expression status of ING3 by quantitative reverse transcription
      polymerase chain reaction. We also examined p53 mutation status and investigated
      its relationship with ING3, as well its clinicopathological characteristics.
      About half of the 71 tumor samples demonstrated downregulation of ING3 compared
      to their matched normal counterparts. Although most clinicopathological variables
      were not significantly related to ING3 downregulation or p53 mutation status, a
      significant relationship was detected in terms of overall survival between the
      cases with low and normal to high ING3 expression. At 5 years follow up,
      approximately 60% of the patients with normal to high ING3 expression survived,
      whereas this was 35% in the patients with low ING3 expression. Multivariate
      analysis also showed downregulation of ING3 as an independent prognostic factor
      for poor overall survival. These results reveal that ING3 would function as a
      potential tumor suppressor molecule and that low levels of ING3 may indicate an
      aggressive nature of head and neck cancer.

PMID- 18081878
TI  - Development of glutathione S-transferase-P-negative foci accompanying nuclear
      factor-erythroid 2-related factor 2 expression during early stage of rat
      hepatocarcinogenesis.
AB  - Glutathione S-transferase P (GST-P), a marker for rat hepatic preneoplastic
      lesions, is suggested to bind to Jun N-terminal kinase (JNK) to repress stress
      response, and GST-P gene expression is regulated by a transcription factor,
      nuclear factor-erythroid 2-related factor 2 (Nrf2). In this study, we examined by
      immunohistochemistry whether JNK2, p38 mitogen-activated protein kinase, and Nrf2
      were expressed in GST-P-positive foci induced by the Solt-Farber protocol. At 2
      weeks after partial hepatectomy, all GST-P-positive foci were negative for p38,
      and 86.4 +/- 5.6% and 64.7 +/- 6.3% of GST-P-positive foci were negative for JNK2
      and Nrf2, respectively. Western blot analysis showed decreased p38 mitogen
      activated protein kinase and JNK2 expression in livers treated with the protocol.
      In immunohistochemistry, besides GST-P-positive foci, GST-P-negative foci were
      detected as p38-negative foci in the surrounding tissues positive for p38. In
      contrast to GST-P-positive foci, most GST-P-negative foci showed enhanced Nrf2
      expression. The number of GST-P-negative foci was 76 +/- 18/10 mm(2) of liver
      section at 2 weeks, but was undetectable at 1 week. The area of GST-P-negative
      foci was 0.09 +/- 0.05 mm(2), smaller than that of GST-P-positive ones (0.29 +/-
      0.23). After treatment with carbon tetrachloride, small vacuoles due to liver
      injury were frequently observed inside GST-P-negative foci but less frequently in
      GST-P-positive foci. However, this treatment resulted in expression of JNK2, p38,
      and Nrf2 in both foci. These results showed development of GST-P-negative foci
      during the early stage of hepatocarcinogenesis and suggested that Nrf2 is not
      responsible for GST-P expression in rat hepatic preneoplastic foci.

PMID- 18081877
TI  - Humoral immune responses in patients vaccinated with 1-146 HER2 protein complexed
      with cholesteryl pullulan nanogel.
AB  - The CHP-HER2 vaccine, comprising truncated 146HER2 protein complexed with
      nanogels of cholesteryl pullulan (CHP), is a novel protein antigen vaccine that
      elicits 146HER2-specific CD8(+) and CD4(+) T-cell immune responses in patients
      with HER2-expressing tumors. We analyzed the humoral responses in patients
      vaccinated with CHP-HER2 and those with CHP-HER2 plus granulocyte-macrophage
      colony-stimulating factor (GM-CSF). The vaccine was injected subcutaneously at a
      dose of 300 microg protein. Nine patients received the vaccine alone over the
      first four injections, followed by CHP-HER2 with GM-CSF or OK-432, whereas six
      received CHP-HER2 plus GM-CSF from the first cycle. 146HER2-specific IgG
      antibodies were induced in 14 patients, who were negative at baseline. The
      antibodies became detectable after the second or third vaccination and reached
      plateau levels after the third or fourth cycle in patients vaccinated with CHP
      HER2 plus GM-CSF. In contrast, the antibodies appeared only after the third to
      sixth vaccination and the plateau appeared after the fourth to eighth cycle in
      patients vaccinated with the CHP-HER2 vaccine alone over the first four cycles.
      The antibodies induced by the vaccine were not reactive with HER2 antigen
      expressed on the cell surface in any of the patients. Epitope analysis using
      overlapping peptides revealed a single region in the 146HER2 protein, amino acids
      127-146, in eight patients who were initially vaccinated with CHP-HER2 alone.
      Similarly, the same HER2 region was recognized dominantly in patients vaccinated
      with GM-CSF. Our results indicate that CHP-HER2 induced HER2-specific humoral
      responses in patients with HER2-expressing tumors and that GM-CSF seems to
      accelerate the responses.

PMID- 18081879
TI  - Sex steroid receptors expression and hormone-induced cell proliferation in human
      osteosarcoma.
AB  - Sex steroid receptors including estrogen receptors (ER), progesterone receptors
      (PR), and androgen receptors (AR) have been sporadically reported in human
      osteosarcoma or its cell lines. Therefore, sex steroids have been considered to
      play some roles in human osteosarcoma, but no systematic and detailed studies
      regarding the correlation between the status of these receptors in sarcoma cells
      and clinicopathological parameters have been reported. We examined the existence
      of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistry. We then
      characterized the potential influence of sex steroids on cell proliferation of
      osteosarcoma cells using MG-63 human osteosarcoma cell line, which expressed all
      of these receptors. ER-beta and PR were detected in the great majority of the
      cases (23 and 24 cases, respectively) but ER-alpha and aromatase were not
      detected in all the cases, and AR was detected only in eight cases. There was a
      significant positive correlation between ER-beta and Ki-67 (MIB1) labeling
      indexes. The absence of aromatase in tumors also suggests the relative importance
      of concentrations of circulating sex steroids. Proliferation of MG-63 cells was
      significantly stimulated by estradiol, progesterone, and 5 alpha
      dihydrotestosterone (DHT), and was significantly suppressed by the addition of
      fulvestrant (ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR
      and AR, respectively. Sex steroids, particularly estrogen and progesterone, are
      considered to play important roles in the regulation of cell proliferation in
      human osteosarcoma. In addition, these data suggest the potential for a novel
      endocrine therapy in osteosarcoma using clinically available inhibitors of
      progesterone and estrogen actions.

PMID- 18081880
TI  - Genetic developments in autoimmune thyroid disease: an evolutionary process.
AB  - The identification of genes placing individuals at an increased risk for the
      development of autoimmune thyroid disease (AITD) has been a slow process.
      However, over the last 20 years or so real progress has been made with the
      mapping of novel loci, via a number of different approaches. First, through the
      use of traditional immunological methods, Human Leucocyte Antigen (HLA)/Major
      Histocompatibility Complex (MHC) was the first gene region to be associated with
      AITD and consistent replications have been reported. Second, the CTLA-4 gene
      region on 2q33 was the first non-MHC replicated locus to be primarily identified
      using the candidate gene method. Third, family-based linkage studies led to the
      mapping of a new type 1 diabetes locus, the PTPN22 gene, which has subsequently
      been independently replicated as a susceptibility gene for Graves' disease (GD).
      Fourth, despite many unsuccessful attempts at implicating the TSHR gene as a
      susceptibility locus for GD, a recent approach of 'tagging' all the common
      variation within the gene has led to its identification as the first GD specific
      locus. Moreover, the use of tag single nucleotide polymorphisms (SNPs) has also
      been used to implicate the recently identified type 1 diabetes locus, CD25 as a
      susceptibility gene for GD. Finally, large scale, ongoing genome-wide association
      studies in multiple autoimmune diseases (AID) states, including AITD seem likely
      to lead to the identification of additional MHC and non-MHC susceptibility loci.

PMID- 18081882
TI  - Medication with antihistamines impairs allergen-specific immunotherapy in mice.
AB  - BACKGROUND: Histamine released from activated mast cells and basophils is an
      important mediator in allergy. Therefore, antihistamines are efficiently and
      widely used to suppress allergic symptoms. OBJECTIVE: This study evaluated the
      role of antihistamines in sensitization against allergens and in the efficiency
      of allergen-specific immunotherapy. METHODS: CBA mice were sensitized and de
      sensitized with bee venom allergen extracts and the major allergen phospholipase
      A2. Clemastine was used to test the effect of a histamine-1 receptor antagonist
      on the immune responses to phospholipase A2. RESULTS: The results demonstrated
      that sensitization against bee venom was strongly enhanced during treatment with
      antihistamines. Clemastine increased IgE production while decreasing IgG2a
      production against bee venom. This T-helper type 2 shift of the humoral response
      appeared to be caused by reduced IFN-gamma and enhanced IL-4 secretion from
      allergen-specific T cells. We also found reduced TNF-alpha, IL-6 and major
      histocompatibility complex class-II expression by macrophages. In sensitized
      mice, the efficiency of allergen-specific immunotherapy was reduced by clemastine
      treatment. CONCLUSION: Antihistamines may enhance allergic sensitization and
      reduce the efficiency of allergen-specific immunotherapy. Future studies will
      need to demonstrate to what extent pre-medication with antihistamine also affects
      allergen-specific immunotherapy in humans.

PMID- 18081881
TI  - Allergological implication of the quaternary hexameric structure of the cockroach
      allergen Per a 3.
AB  - BACKGROUND: Cockroach allergens play a very important role in allergic diseases,
      especially asthma. The major allergen of the American cockroach (Periplaneta
      americana), Per a 3, naturally occurs as isoforms of hexamers. OBJECTIVE: The aim
      of this study was to investigate whether the hexameric structures of Per a 3
      influence their allergenicity and immunogenicity. METHODS: Therefore, we compared
      the different effects of native hexamers and dissociated monomers of cockroach
      haemolymph (HL), containing almost only Per a 3 proteins (HL-Per a 3), on
      proliferation and T-helper type 1 (Th1)/Th2 cytokine production of human CD4(+) T
      cells in co-culture with allergen-pulsed monocyte-derived autologous dendritic
      cells (DC) as well as the leukotriene release of basophils. RESULTS: In P.
      americana-sensitized and non-sensitized donors the HL-Per a 3 monomers were
      internalized faster by immature DC and induced higher proliferation and IFN-gamma
      production than the hexamers. While in non-sensitized donors IL-4 and IL-5 as
      well as IL-10 production were also increased after stimulation with monomeric HL
      Per a 3-pulsed DC, Th2 cytokine and IL-10 production were only enhanced in P.
      americana-sensitized donors using hexameric HL-Per a 3-pulsed DC. Furthermore, in
      the leukotriene release assay the monomers were less effective than the hexamers.
      CONCLUSION: Our data indicate that the quaternary structure can influence both
      allergenicity and immunogenicity, also depending on the sensitization status. The
      monomeric variant of Per a 3 allergens could be a possible candidate for a
      specific immunotherapy because the IgE-mediated allergic reaction and the Th2
      inducing capacity are diminished while the Th1-inducing capacity is retained.

PMID- 18081883
TI  - Primary prevention of allergy: avoiding risk or providing protection?
AB  - Primary prevention strategies of allergy so far have been aimed to fight allergy
      causes, by avoiding risk factors and inhibiting their mechanisms of action. The
      results of trials testing food or airborne allergen avoidance as a prevention
      strategy were, however, rather disappointing. A reverse approach for primary
      prevention of allergies aims to facilitate exposure to protecting factors which
      promote the induction of immunologic tolerance against innocuous antigens. These
      factors are associated with farming environment and a 'traditional lifestyle',
      but identification of these factors is quite difficult. Major candidates include
      food-borne microbes, helminths or their components, which are able to stimulate
      mucosal immunity, particularly in the gut. Similarly, new preventive and
      therapeutic strategies are being tested to induce specific food-allergen oral
      tolerance through the ingestion of progressively increasing doses of the
      offending food. This shifting of allergy prevention research from avoidance to
      tolerance induction will hopefully allow us to reverse the epidemic trend of
      allergy diseases.

PMID- 18081885
TI  - Combined effects of hypoxia and endurance training on lipid metabolism in rat
      skeletal muscle.
AB  - AIM: To determine whether endurance training can counterbalance the negative
      effects of hypoxia on mitochondrial phosphorylation and expression of the long
      chain mitochondrial fatty acid transporter muscle carnitine palmitoyl transferase
      1 (mCPT-1). METHODS: Male Wistar rats were exposed either to hypobaric hypoxia
      (at a simulated altitude of approximately 4000 m, PIO(2) approximately 90 mmHg)
      or to normoxia (sea level) for 5 weeks. In each environment, rats were randomly
      assigned to two groups. The trained group went through a 5-week endurance
      training programme. The control group remained sedentary for the same time
      period. Muscle fatty acid oxidation capacity was evaluated after the 5-week
      period on isolated mitochondria prepared from quadriceps muscles with the use of
      palmitoylcarnitine or pamitoylCoA + carnitine. RESULTS: Chronic hypoxia decreased
      basal (V(0), -31% with pamitoylCoA + carnitine and -21% with palmitoylcarnitine,
      P < 0.05) and maximal (V(max), -31% with pamitoylCoA + carnitine, P < 0.05)
      respiration rates, hydroxyacylCoA dehydrogenase activity (-48%, P < 0.05), mCPT-1
      activity index (-34%, P < 0.05) and mCPT-1 protein content (-34%, P < 0.05). Five
      weeks of endurance training in hypoxia brought V(0), mCPT-1 activity index and
      mCPT-1 protein content values back to sedentary normoxic levels. Moreover, in the
      group trained in hypoxia, V(max) reached a higher level than in the group that
      maintained a sedentary lifestyle in normoxia (24.2 nmol O(2). min(-1) . mg(-1)
      for hypoxic training vs. 19.9 nmol O(2) . min(-1) . mg(-1) for normoxic
      sedentarity, P < 0.05). CONCLUSION: Endurance training can attenuate chronic
      hypoxia-induced impairments in mitochondrial fatty acid oxidation. This training
      effect seems mostly mediated by mCPT-1 activity rather than by mCPT-1 content.

PMID- 18081884
TI  - Hormonal regulation of renomedullary hyaluronan.
AB  - AIM: Hyaluronan (HA) is involved in renomedullary water handling through its
      water-binding capacity. This study addressed the effect of hormones involved in
      regulating fluid-electrolyte homeostasis on renomedullary HA content in vivo and
      in vitro. METHODS: The kidneys from rats treated with L-NAME, indomethacin,
      vasopressin (AVP) or methylprednisolone (MP) during euvolaemia or water loading
      were analysed for HA by RIA, ELISA and histochemical staining. HA was measured in
      renomedullary interstitial cells treated with AVP, angiotensin II (Ang II) or a
      combination of AVP and Ang II. RESULTS: Baseline renal cortical and medullary HA
      content was unaffected by 2 h of intravenous treatment with L-NAME (NOS
      inhibitor) or indomethacin (cyclo-oxygenase inhibitor), whereas AVP reduced
      medullary HA by 33%. During 2 h of acute water loading, diuresis was accompanied
      by an increase in renomedullary HA (+45%), but cortical HA was unaffected. In
      both L-NAME- and indomethacin-treated animals, the water loading-induced increase
      in renomedullary HA was absent, indicating involvement of NO and prostaglandins.
      After 7 days of MP treatment, medullary HA was reduced by 40%, but the water
      loading-induced elevation in HA remained. In cultured renomedullary interstitial
      cells, AVP reduced the HA content in the supernatant by 63%, and simultaneous
      treatment with Ang II reduced the HA content even further (95%). CONCLUSION: AVP
      reduces HA content, and NO and prostaglandins are needed for the increase in HA
      during water loading.

PMID- 18081886
TI  - Regulation of the human serotonin transporter mediated by long-term action of
      serotonin in Caco-2 cells.
AB  - AIM: The aim of this study was to determine the effect of long-term serotonin (5
      hydroxytryptamine, 5-HT) treatment on the human serotonin transporter (hSERT)
      function and its expression. METHODS: This study was carried out in the
      enterocyte-like cell line Caco-2. These cells constitutively express the hSERT
      and have been shown to be an excellent model for the study of this protein. We
      measured serotonin transport, levels of mRNA expression and of the SERT protein
      after treating the cells with serotonin. RESULTS: Serotonin treatment diminished
      hSERT activity in a concentration and period-dependent way by increasing the K(t)
      value and reducing V(max). This inhibition was reversible and was not mediated by
      either the action of 5-HT(2), 5-HT(3) or 5-HT(4) receptors, or by the
      intracellular second messengers, protein kinase C and cAMP. 5-HT did not seem to
      affect either the mRNA level of the SERT or the protein transporter measured in
      either the membrane or the cell lysate. The 5-HT treatment effect was additive to
      the inhibitory effect of treatment with a low concentration of citalopram and
      fluoxetine. Nevertheless, 5-HT did not increase the inhibition yielded by
      treatment with high concentration citalopram. CONCLUSION: The chronic increase in
      serotonin in the extracellular medium diminishes the function of the SERT. This
      effect seems to be due to an effect on the transporter molecule itself in the
      membrane, without altering protein synthesis, intracellular traffic, or its
      availability.

PMID- 18081887
TI  - Increased extracellular 5-HT but no change in sleep after perfusion of a 5-HT1A
      antagonist into the dorsal raphe nucleus of rats.
AB  - AIM: The 5-HT(1A) receptor antagonist 4-Iodo-N-[2-[4-(methoxyphenyl)-1
      piperazinyl]ethyl]-N-2-pyridinyl-benzamide hydrochloride (p-MPPI) (10 microM) was
      perfused into the dorsal raphe nucleus (DRN) to study simultaneously the effects
      of the drug on the DRN and frontal cortex extracellular serotonin (5
      hydroxytryptamine, 5-HT) levels and concurring behavioural states. METHODS:
      Waking, slow wave sleep and rapid eye movement sleep were determined by
      polygraphic recordings during microdialysis perfusion and extracellular sample
      collection. The samples were analysed by microbore high-performance liquid
      chromatography coupled with electrochemical detection for analysis of 5-HT.
      RESULTS: p-MPPI perfusion into the DRN (n = 6) produced a sixfold 5-HT increase
      in the DRN during all behavioural states. The increased 5-HT level was most
      likely related to the blockage of 5-HT(1A) receptors in the DRN by p-MPPI. No
      significant effect was seen on sleep. CONCLUSION: Despite the dramatic increase
      in DRN extracellular 5-HT produced by p-MPPI, only a transient and nonsignificant
      effect on sleep was recorded. It is suggested that the usual coupling between 5
      HT level and behavioural state may be lost when an excessive serotonergic output
      is pharmacologically achieved.

PMID- 18081889
TI  - Childhood precursor B-cell acute lymphoblastic leukaemia and monosomy 7 with
      phenotypic shift at relapse; evidence for the stem cell origins of monosomy 7.

PMID- 18081888
TI  - Heat shock factor activation in human muscles following a demanding intermittent
      exercise protocol is attenuated with hyperthermia.
AB  - AIM: The present study investigated whether increased activation of heat shock
      factors (HSF) following exercise relates primarily to the increased muscle
      temperature or to exercise in general. METHODS: Six subjects completed 40 min of
      intermittent cycling (15s:15s exercise:recovery at 300 +/- 22 W) at an ambient
      temperature of either 20.0 +/- 1.3 or 40.3 +/- 0.7 degrees C. Muscle biopsies
      were taken prior to and immediately following the exercise protocol with samples
      analysed for HSF DNA binding by electrophoretic mobility shift assay. RESULTS:
      Exercise at 40 degrees C resulted in significantly increased oesophageal (39.3 +/
      0.2 degrees C) and muscle temperature (40.0 +/- 0.2 degrees C) at the end of the
      exercise protocol compared with 20 degrees C (oesophageal, 38.1 +/- 0.1 degrees
      C; muscle, 38.9 +/- 0.2 degrees C). However, an increased DNA binding of HSF was
      not evident following exercise at 40 degrees C (reduced by 21 +/- 22%) whereas it
      increased by 29 +/- 51% following exercise at 20 degrees C. CONCLUSION: It
      appears that increased temperature is not the major factor responsible for
      activation of HSF DNA binding.

PMID- 18081890
TI  - Intracranial haemorrhage in haemophilia A and B.
AB  - In countries with a good standard of health care, intracranial haemorrhage (ICH)
      during the neonatal period affects 3.5-4.0% of all haemophilia boys, which is
      considerably (40-80 times) higher than expected in the normal population. ICHs
      are also frequent after the neonatal period, affecting 3-10% of the haemophilia
      population who are mainly treated on demand. The risk is higher in inhibitor
      patients. Spontaneous haemorrhage is reported more frequently than trauma-induced
      haemorrhage in most studies. The prevalence of ICH in patients treated with a
      prophylactic regimen is not known. Although more frequent in younger patients, a
      substantial proportion of ICH occur in adults, suggesting that general risk
      factors because of age, such as hypertension, are increasingly important as the
      haemophiliac gets older. Some studies have reported a substantial proportion of
      ICH affecting patients with milder forms of haemophilia. The risk of ICH has to
      be considered when discussing treatment strategies for haemophilia patients.

PMID- 18081891
TI  - Bleeding into an emphysematous bulla.

PMID- 18081892
TI  - Arsenic trioxide induces de novo protein synthesis of annexin-1 in neutrophils:
      association with a heat shock-like response and not apoptosis.
AB  - We recently demonstrated that arsenic trioxide (ATO) induced apoptosis in human
      neutrophils and increased de novo protein synthesis. Here, we identified one of
      these newly synthesized proteins as annexin-1 (AnxA1), a protein recently found
      to be proapoptotic in neutrophils when added exogenously. AnxA1 was detected at
      the cell membrane of ATO-induced neutrophils as well as in the supernatants.
      Using neutrophils harvested from AnxA1 knockout mice, we found that the
      proapoptotic activity of ATO was similar in neutrophils, regardless of AnxA1
      levels. A second protein was identified as heat shock protein (Hsp) 89alpha.
      Because ATO is known to induce a HS-like response in a variety of cells, we
      investigated its ability to induce gene expression of Hsp in neutrophils and
      found that ATO increases HSP90AA1, HSPA1 and HSPB1 mRNA in these cells. We
      conclude that ATO-induced neutrophil apoptosis by an AnxA1-independent mechanism.
      Our data provide the first evidence that ATO induces a stress response in human
      neutrophils and that de novo synthesis of AnxA1 is related to this event rather
      than to the proapoptotic activity of ATO.

PMID- 18081893
TI  - Identification of a thrombin-interactive site within the FVIII A2 domain that is
      responsible for the cleavage at Arg372.
AB  - FVIII is activated by cleavage at Arg(372), Arg(740), and Arg(1689) by thrombin.
      This study showed that an anti-A2 monoclonal antibody, with a specific epitope
      for residues 484-509, and anti-FVIII inhibitor alloantibodies with similar A2
      epitopes, inhibited thrombin-catalyzed FVIII activation. Sodium dodecyl sulphate
      polyacrylamide gel electrophoresis analysis showed that cleavage at Arg(372) but
      not at Arg(740) occurred at approximately fourfold decreased rate in the presence
      of anti-A2 antibody. Peptide 484-509 also inhibited co-factor activation,
      consistent with inhibition of cleavage at Arg(372). Direct binding studies using
      active-site modified thrombin showed that a 484-509 peptide as well as the anti
      A2 antibodies blocked the A2-thrombin binding. Furthermore, covalent cross
      linking was observed between the 484-509 peptide and thrombin following reaction
      with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. Mutant A2 molecules in which
      the clustered basic residues in this sequence were converted to alanine were used
      to assess the binding reactions in a surface plasmon resonance-based assay.
      Mutants R484A, R489A, R490A, H497A and K499A possessed two to fivefold lower
      affinity than wild-type A2. These findings demonstrate that clustered basic
      residues within the 484-509 region of the A2 domain play a part of key role in
      thrombin-binding, which is responsible for thrombin-catalyzed FVIII activation by
      cleavage at Arg(372).

PMID- 18081894
TI  - Endothelial hyperplasia and endothelial galectin-3 expression are prognostic
      factors in primary central nervous system lymphomas.
AB  - Recently, considerable attention has been focused on the identification of
      clinically relevant prognostic markers for primary central nervous system
      lymphomas (PCNSL). The present study investigated whether three morphological
      features, i.e. necrosis, reactive perivascular T-cell infiltrate and endothelial
      hyperplasia, and galectin-1 and galectin-3 immunohistochemical expression have
      prognostic roles in a series of 58 PCNSL samples from 44 immunocompetent and 14
      immunocompromised patients. The presence of endothelial hyperplasia (identified
      in 21% of the assessable cases) was identified as a bad prognostic factor for
      immunocompetent PCNSL patients, whereas the other morphological features were not
      associated with any prognostic value. Lymphomatous cells of eight PCNSL cases
      expressed galectin-3 without any prognostic value, and lymphomatous cells did not
      express galectin-1. In contrast, endothelial expression of galectin-3 was
      identified (by means of uni- and multi-variate analyses) as a bad prognostic
      factor for immunocompetent PCNSL patients. In addition, a combination of
      endothelial hyperplasia and/or endothelial galectin-3 expression was shown to be
      an independent prognostic factor for immunocompetent PCNSL patients treated with
      methotrexate-based chemotherapy. In summary, this study suggests that endothelial
      related markers can identify risk groups of PCNSL patients and indicates that
      galectin-3 could be involved in PCNSL angiogenesis.

PMID- 18081895
TI  - Severity of psoriasis and health-related quality of life: the moderating effects
      of temperament.

PMID- 18081896
TI  - Successful use of etanercept in type I pityriasis rubra pilaris.

PMID- 18081897
TI  - Childhood lichen planus after simultaneous measles-mumps-rubella and diphtheria
      tetanus-pertussis-polio vaccinations.

PMID- 18081898
TI  - Tungiasis: eggs seen with dermoscopy.

PMID- 18081899
TI  - Two-year follow-up of posterior capsule opacification after implantation of a
      hydrophilic or hydrophobic acrylic intraocular lens.
AB  - PURPOSE: To evaluate posterior capsule opacification (PCO) 2 years after cataract
      surgery following implantation of a hydrophilic or a hydrophobic single-piece
      acrylic intraocular lens (IOL) with a sharp edge. METHODS: Phacoemulsification
      cataract surgery was performed in one eye of 120 patients with senile cataract in
      this prospective study. They were randomized to implantation of either a
      hydrophilic acrylic IOL (BL27; Bausch & Lomb, Rochester, NY, USA) or a
      hydrophobic acrylic IOL (AcrySof) SA60AT; Alcon Laboratories, Fort Worth, TX,
      USA). Two years after surgery, retroillumination images were obtained and PCO
      area and severity were evaluated using pocoman software. Best corrected visual
      acuity (VA) (both high-contrast [100%] and low-contrast [2.5%]), glare, laser
      flare and intraocular pressure were measured. Capsulotomy rates were recorded.
      RESULTS: Patients implanted with the hydrophilic IOL had a greater percentage
      area and severity of PCO compared with patients with the hydrophobic IOL (p <
      0.001). There was no difference in PCO between men and women in the hydrophilic
      group. However, in the hydrophobic group, women had significantly more PCO than
      men (p < 0.05). Patients with the hydrophobic acrylic IOL had better high- and
      low-contrast visual activity (VA) (p < 0.01) and less glare (p < 0.001) than
      those with a hydrophilic acrylic IOL. Of the patients with the hydrophilic IOL,
      42% underwent capsulotomy, compared with 10% in the hydrophobic group (p <
      0.001). CONCLUSIONS: Two years after surgery, patients with the SA60AT
      hydrophobic acrylic IOL had less PCO and better high- and low-contrast VA than
      patients with the BL27 hydrophilic acrylic IOL.

PMID- 18081900
TI  - Diagnostic compatibility of structural and haemodynamic parameters in open-angle
      glaucoma patients.
AB  - PURPOSE: Current evidence indicates that alteration in ocular blood flow may be
      relevant in open-angle glaucoma (OAG) patients independent of intraocular
      pressure (IOP). Presently, the lack of an adequate methodology capable of
      assessing all vascular beds limits the clinical role of blood flow parameters in
      glaucoma management. We aimed to compare differences in retinal nerve fibre layer
      (RNFL) thickness and retrobulbar haemodynamics between OAG patients and healthy
      age-matched control subjects. METHODS: Sixty eyes of 30 OAG patients and 30
      healthy age-matched controls were enrolled into the prospective, randomized
      study. Retinal nerve fibre layer thickness was analysed by scanning laser
      polarimetry (SLP). Standard SLP parameters were determined, including: average
      temporal, superior, nasal, inferior thickness (TSNIT); superior and inferior
      averages; TSNIT standard deviation (TSNIT-SD), and nerve fibre indicator (NFI).
      Retrobulbar haemodynamics were assessed using colour Doppler imaging (CDI). Peak
      systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility index (PI) and
      resistivity index (RI) in the ophthalmic artery (OA), central retinal artery
      (CRA) and short posterior ciliary artery (SPCA) were evaluated. RESULTS: The RNFL
      in OAG patients was statistically significantly thinner compared with that in age
      matched controls: the NFI was 24.9 +/- 10.24 in OAG patients and 16.13 +/- 7.95
      in healthy controls (p < 0.05). Statistically significant differences were
      observed: CRA PSV was 20.54 +/- 7.84 cm/second in OAG subjects and 16.5 +/- 6.19
      cm/second in healthy controls (p = 0.0038); OA EDV was 8.99 +/- 4.71 cm/second in
      OAG subjects and 5.93 +/- 3.23 cm/second in healthy controls (p = 0.0048).
      Correlation analysis of NFI was in positive association with CRA EDV (r = 0.395;
      p < 0.05) and CRA PI (r = 0.403; p < 0.05) in OAG subjects, but no statistically
      significant association was seen in healthy controls. CONCLUSIONS: Statistically
      significant thinning of the RNFL in association with reduced retrobulbar blood
      flow velocities was observed in OAG patients. Combining ocular structural
      alterations with ocular circulation assessment may increase our ability to
      elucidate potential IOP-independent glaucomatous risk factors.

PMID- 18081901
TI  - Incidence and clinical characteristics of symptomatic choroidal metastasis from
      lung cancer.
AB  - PURPOSE: To determine the clinical characteristics of symptomatic choroidal
      metastasis (CM) resulting from metastatic lung cancer. METHODS: Twenty-two
      consecutive patients with symptomatic CM resulting from lung cancer were
      retrospectively reviewed for ocular findings, medical history and systemic
      disease. All patients underwent a complete screening for further organ metastasis
      by computed tomography (CT) and bone scintigraphy. Annual frequency of CM was
      determined and compared with the incidence predicted from ocular screening
      studies. RESULTS: In eight of 22 (36%; 95% confidence interval [CI] 17-59)
      patients, lung cancer had been diagnosed before occurrence of CM, with a median
      interval of 13 months. In 14 patients lung cancer was detected after diagnosis of
      CM, with a median interval of 1 month. Choroidal metastasis was unilateral,
      solitary and located close to or at the posterior pole in the majority of
      patients. Further organ metastasis with a median number of three affected organ
      systems was present in 19 (86%; 95% CI 65-97) patients. Median survival after
      diagnosis of symptomatic CM was 13 months, by contrast with 2 months in lung
      cancer patients with CM identified in an ocular screening study. The mean number
      of patients in Berlin diagnosed with symptomatic CM was 1.4 per year, which was
      two orders of magnitude less than predicted from screening studies. CONCLUSIONS:
      Symptomatic choroidal lung cancer metastasis in the majority of patients presents
      as a solitary tumour before diagnosis of lung cancer in patients with multiple
      organ systems affected by metastatic disease. Contrary to predictions from ocular
      screening studies, it is a rare clinical entity.

PMID- 18081902
TI  - Polyglactin sutures versus nylon sutures for suturing of conjunctival autograft
      in pterygium surgery.

PMID- 18081903
TI  - Vasopressin in catecholamine-refractory shock in children.
AB  - Severe septic and cardiogenic shock is associated with a high mortality in
      neonates, children and adolescents. Common therapies include the administration
      of fluids and the use of conventional inotropes. However, in severe forms of
      shock, cardio-circulatory failure may be secondary to profound vasoparalysis and
      unresponsive to conventional therapies. We reviewed the literature on the use of
      arginine-vasopressin (AVP) and terlipressin (TP) as a rescue therapy in neonates,
      children and adolescents with catecholamine-refractory shock or cardio
      circulatory arrest. We identified 17 reports (11 case series, 6 case reports) on
      a total of 109 patients. Only two studies were prospective. The age of treated
      patients ranged from extremely low birth weight infants of 23 weeks' gestation to
      a 19-year-old adolescent. The most common indication for either drug was
      catecholamine-refractory septic shock (nine reports). Commonly reported responses
      following AVP/TP administration were a rapid increase in systemic arterial blood
      pressure, an increase in urine output, and a decrease in serum lactate. In most
      reports, AVP and TP had a significant impact on the required dose of inotropes
      which could be reduced. Despite the use of AVP/TP, mortality was high (52/109).
      In view of the limited number of paediatric patients treated with AVP/TP, no
      definite recommendations on their use in children with severe forms of cardio
      circulatory failure can be issued. There is a need for larger prospective trials
      assessing the efficacy and safety profiles of these drugs in a defined setting.
      Until more data are available, and taking into consideration the detrimental
      impact catecholamine-refractory shock has on children, the use of AVP/TP as a
      rescue therapy should be considered on an individual basis.

PMID- 18081904
TI  - Intravitreal bevacizumab for vitreous haemorrhage.

PMID- 18081905
TI  - Intravitreal and intracameral bevacizumab to treat neovascular complications of
      retinopathy of prematurity.

PMID- 18081906
TI  - Is poor glycaemic control in diabetic patients a risk factor of myopia?
AB  - PURPOSE: As a consequence of an increasing prevalence of short-sightedness
      (myopia) in countries that have adopted western dietary patterns, it has been
      hypothesized that hyperglycaemia and hyperinsulinaemia induce myopia. The purpose
      of this study was to evaluate the relation between glycosylated haemoglobin
      (HbA(1c)), insulin dosage and myopia in diabetic patients. METHODS: All type 1
      diabetic patients aged 16-26 years [mean age 22.0, standard deviation (SD) 2.9]
      attending the eye clinic at Steno Diabetes Center, Copenhagen, in 1995-1997 were
      included in the study (n = 393). The following data were collected from the
      medical records from baseline to 2005: age at diabetes onset, age at baseline,
      sex, weight, HbA(1c), insulin dosage, refractive error, visual acuity and ocular
      diabetes complications. RESULTS: The prevalence of myopia [spherical equivalent
      (SE) < or = -0.5 D] was 53.3% [95% confidence interval (CI) +/- 5.29] at
      baseline. We followed 252 patients for 7.1 years (SD 2.2). In a logistic
      regression analysis, age at baseline [odds ratio (OR) 0.90 (95% CI 0.82; 0.99), P
      = 0.031], duration of diabetes at baseline [OR 0.95 (95% CI 0.91; 0.99), P =
      0.047] and HbA(1c) [OR 1.26 (95% CI 1.03; 1.47), P = 0.022] were associated with
      myopia. The relative risk of a myopic shift was 1.7 (95% CI 1.28; 2.26) in
      patients aged 16-21 years and 1.6 (95% CI 1.19; 2.14) in patients with HbA(1c)
      above 8.8%. Insulin dosage was not related to myopia. CONCLUSION: The prevalence
      of myopia in diabetic patients is considerably higher than in the background
      Danish population. Poor metabolic control of glucose is a suggested risk factor
      of myopia. The study suggests that myopia may be regarded as a complication of
      hyperglycaemia in diabetes.

PMID- 18081908
TI  - Effect of driver distraction and low alcohol concentrations on useful field of
      view and frequency-doubling technology perimetry.
AB  - PURPOSE: To investigate the effects of a mental psychometric task that simulates
      the distraction effect of a hands-free mobile phone and of low alcohol
      concentrations (0.3-0.5 g/l) on two tests: the useful field of view (UFOV) and
      frequency-doubling technology (FDT) perimetry. METHODS: Thirty-seven healthy
      young vehicle drivers aged 22 +/- 3 years were subjected to a computer version of
      the UFOV test and FDT perimetry, undertaken according to a counterbalanced within
      subject design. The tests were performed in two sessions (an 'alcohol session'
      and a 'sober session'), while undertaking or not undertaking a psychometric test
      [the Paced Auditory Serial Addition Test (PASAT)] to simulate the effect of
      distraction. Each subject was instructed to concentrate on the PASAT while taking
      each test. RESULTS: UFOV scores were affected when the PASAT was performed
      simultaneously (P < 0.0001) in that longer times were required to identify a
      central target and the location of a peripheral target. FDT perimetry was
      affected by the addition of the PASAT, with a significant reduction in mean
      sensitivity and a localized sensitivity loss [pattern standard deviation (PSD) >6
      dB]. Test times, false-positive and negative catch trial responses were all
      increased. However, the UFOV test and FDT perimetry results were not
      significantly affected by a low alcohol concentration. CONCLUSION: Distraction
      significantly affects performance in the UFOV test and frequency-doubling
      technology perimetry. Our findings suggest that using a hands-free mobile phone
      while driving may lead to a low-to-moderate crash risk in young adults with
      normal visual function.

PMID- 18081909
TI  - Encephalopathy induced by levetiracetam added to valproate.
AB  - BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced
      encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy
      with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA)
      (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per
      6 months to two per month. Neuropsychological testing showed impaired word
      fluency, psychomotor speed and working memory. The interictal
      electroencephalogram (EEG) showed a generalized slowing to 5 per second theta
      rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following
      discontinuation of LEV, EEG and neuropsychological findings improved and seizure
      frequency decreased.

PMID- 18081910
TI  - The reliability of the MSFC and its components.
AB  - BACKGROUND: The Multiple Sclerosis Functional Composite (MSFC) is a
      multidimensional measurement tool for multiple sclerosis (MS) including a measure
      of ambulation (Timed 25-foot Walk [TWT]), arm function (Nine-Hole Peg Test
      [9HPT]) and cognition (Paced Auditory Serial Addition Test [PASAT]). OBJECTIVES:
      To assess the reliability and practice effects in the Finnish version of the MSFC
      and its components. MATERIALS AND METHODS: Ten relapsing-remitting MS patients
      and 10 healthy controls underwent five testing sessions with the MSFC over a 4
      week period. RESULTS: The MSFC showed excellent intra- (0.99) and inter-rater
      (1.0) reliability. The MSFC, especially the 9HPT and the PASAT showed significant
      practice effects. On the 9HPT the controls remained stable whereas the patients
      improved their performance; on the PASAT both groups improved. CONCLUSIONS: The
      MSFC showed excellent intra- and inter-rater reliability although the 9HPT and
      the PASAT were prone to considerable practice effects.

PMID- 18081911
TI  - No benefit of treatment with cyclophosphamide and autologous blood stem cell
      transplantation in multifocal motor neuropathy.
AB  - INTRODUCTION: Patients with multifocal motor neuropathy (MMN) usually respond to
      intravenous immunoglobulin (IVIG), but because of the short-lasting effect the
      treatment must be given repeatedly. Remission after treatment with high-dose
      cyclophosphamide has recently been reported in one patient refractory to IVIG.
      CASE REPORT: Here we report on a patient who responded to IVIG, but temporarily
      deteriorated dramatically after treatment with high-dose cyclophosphamide and
      autologous blood stem cell transplantation. Today the situation is the same as
      before the treatment with cyclophosphamide and blood stem cell transplantation,
      i.e. IVIG is given every 4 weeks. CONCLUSION: Our patient did not benefit from
      the treatment with high-dose cyclophosphamide and autologous blood stem cell
      transplantation. The effect of treatment with high-dose cyclophosphamide in MMN
      seems to be difficult to predict and that should be paid attention to if this
      type of treatment is considered.

PMID- 18081912
TI  - Is spinal epidural lipomatosis an MRI-based diagnosis with clinical implications?
      A retrospective analysis.
AB  - OBJECTIVES: Magnetic resonance imaging (MRI) is considered the most sensitive
      modality for evaluating spinal epidural lipomatosis (SEL) in vivo. The aim of
      this study was to compare the existing MRI classifications of SEL and to
      reevaluate the clinico-radiological correlation of SEL as a pathological entity.
      MATERIALS AND METHODS: Measurements of the cervical, thoracic and lumbar spine
      were performed in a retrospective setting within 1406 data sets from the digital
      MRI archives. RESULTS: It could be shown that the existing MRI classifications
      developed for different spinal regions complemented each other. However, there
      was no distinct correlation of these MRI findings with clinical symptoms because
      other morphological changes existed that probably caused the patients'
      complaints. CONCLUSION: Existing SEL classifications developed either for the
      lumbar or the thoracic spine were found to be applicable to both regions, but the
      very vague association with clinical symptoms should caution against premature
      conclusions with respect to the clinical significance of SEL.

PMID- 18081913
TI  - Costs of brain disorders in Finland.
AB  - OBJECTIVE: To calculate the costs of brain disorders on the national level.
      METHODS: Electronic data bases, national registers and internet data. RESULTS:
      Any brain disorder was estimated to affect a fifth of the Finnish population. The
      three most common disorders were migraine, anxiety disorder and affective
      disorder. The total costs of brain disorders constituted 3% of the national gross
      product, or 45% of all the health-care costs. However, this is likely a
      conservative estimate, because not all chronic brain disorders and not all costs
      were included. Of the total costs of brain disorders, 32% were for direct health
      care, 23% for indirect medical care and 45% for indirect costs. Dementia was the
      most costly individual brain disorder followed by addiction and affective
      disorders. Most costly per case were brain tumours and multiple sclerosis.
      CONCLUSION: Brain disorders constitute a costly part of the population's health
      costs. Directed preventive measures are needed to counteract the population
      morbidity and to control the increasing cost pressure in health care.

PMID- 18081914
TI  - MxA protein assay for optimal monitoring of IFN-beta bioactivity in the treatment
      of MS patients.
AB  - OBJECTIVES: Myxovirus resistance protein A (MxA) can be used as a marker of the
      bioactivity of interferon-beta (IFN-beta) therapy. Two to forty per cent of IFN
      beta-treated multiple sclerosis (MS) patients develop IFN-beta-neutralizing
      antibodies (NAb) with subsequent attenuation of MxA protein induction. The aim of
      this study was to set up a simple MxA enzyme immunoassay (EIA) for the
      measurement of MxA protein and to evaluate the EIA test by comparing the results
      with flow cytometric analysis and the measurement of NAb. METHODS: total of 51
      IFN-beta-treated relapsing-remitting MS (RRMS) patients were tested for MxA
      protein expression by using both MxA EIA assay and flow cytometric analysis.
      Thirteen patients were confirmed to be NAb-positive. RESULTS: The correlation
      between EIA and flow cytometric analysis was significant with a wider range of
      measured levels in the EIA. Patients with NAb had low MxA levels, but in some
      patients, remaining MxA induction could be detected despite NAb. CONCLUSIONS: The
      MxA EIA assay seems to be a practical method for large-scale analysis of the
      bioactivity of IFN-beta treatment.

PMID- 18081915
TI  - Clinical predictors in patients with refractory epilepsy exposed to
      levetiracetam: a single-center study.
AB  - OBJECTIVES: This aim of the study was to ascertain the importance of clinical
      parameters on the response to treatment in refractory epilepsy patients on
      levetiracetam (LEV). MATERIALS AND METHODS: We retrospectively evaluated medical
      records of 132 patients aged 17-78 years with refractory epilepsy (defined as a
      failure of at least two antiepileptic drugs due to the lack of efficacy) exposed
      to LEV. We analyzed the response (seizure freedom or continuing LEV) using
      logistic regression. RESULTS: Of 132 patients exposed to LEV, 103 cases continued
      the drug. Of the discontinuations (29/132), 75% were for lack of efficacy and 25%
      for tolerability problems. Twenty-three percent of the previously refractory
      patients achieved seizure freedom for at least 1 year with LEV in combination
      therapy. The dose of LEV in 80% of seizure-free patients was 1000 mg/day or less.
      The duration of epilepsy, age and sex were not associated with response to LEV.
      Seizure freedom was associated with epileptic syndrome or etiology. If no
      specific syndrome was recognized, there was a significantly greater chance for
      response compared with temporal lobe epilepsy (OR 20.76; 95% CI 2.12-203.61).
      CONCLUSIONS: Our study was based on the careful clinical evaluation of the
      patients with extensive use of video EEG (50%) and MRI scans (95%). These
      clinical predictors were evasive in previous studies. This study showed that they
      are worth pursuing but significantly larger groups of patients need to be
      investigated to reach significant findings.

PMID- 18081916
TI  - Tilt table testing in patients with suspected epilepsy.
AB  - BACKGROUND: Approximately 20-30% of patients with epilepsy are misdiagnosed and
      syncope often seems to be the mistaken cause. We re-evaluated patients referred
      to an epilepsy clinic where suspicion of neurally mediated (reflex) syncope were
      raised using tilt table testing (HUT). METHODS: HUT laboratory results and
      medical records of 120 consecutive patients were reviewed retrospectively over a
      period of 27 months. RESULTS: HUT was positive in 59 (49%) patients. Seventeen of
      38 (45%) patients previously diagnosed with epilepsy and taking antiepileptic
      drugs were found to be misdiagnosed. Four of 21 patients with epilepsy (19%) had
      dual diagnoses of reflex syncope and epilepsy. CONCLUSION: HUT is an informative
      investigation when suspicions of reflex syncope are raised in patients referred
      to an epilepsy clinic. Reflex syncope is an important and common differential
      diagnosis of epilepsy.

PMID- 18081918
TI  - A critical review of candidacy for orthotopic liver transplantation in alcoholic
      liver disease.
AB  - The majority of candidates with end-stage alcoholic liver disease (ESALD) in the
      United States who are eligible for referral for liver transplantation (LT) are
      not being referred. There is a lack of firm consensus for the duration of
      abstinence from alcohol as well as what constitutes good psychosocial criteria
      for listing for LT. Evidence shows that the general public and the practicing
      physicians outside the transplant community perceive that patients with a history
      of alcohol abuse will make poor transplant candidates. However, physicians in the
      transplant community perceive selected patients with ESALD as good candidates.
      When considering patients for listing for LT, 3 months of alcohol abstinence may
      be more ideal than 6 months. Patients with a lack of social support, active
      smoking, psychotic or personality disorders, or a pattern of nonadherence should
      be listed only with reservation. Those who have a diagnosis of alcohol abuse as
      opposed to alcohol dependence may make better transplant candidates. Patients who
      have regular appointments with a psychiatrist or psychologist in addictions
      treatment training also seem to do more favorably.

PMID- 18081917
TI  - Evaluation of the NK2 homeobox 1 gene (NKX2-1) as a Hirschsprung's disease locus.
AB  - Hirschsprung's disease (HSCR, colonic aganglionosis) is an oligogenic entity that
      usually requires mutations in RET and other interacting loci. Decreased levels of
      RET expression may lead to the manifestation of HSCR. We previously showed that
      RET transcription was decreased due to alteration of the NKX2-1 binding site by
      two HSCR-associated RET promoter single nucleotide polymorphisms (SNPs). This
      prompted us to investigate whether DNA alterations in NKX2-1 could play a role in
      HSCR by affecting the RET-regulatory properties of the NKX2-1 protein. Our
      initial study on 86 Chinese HSCR patients revealed a Gly322Ser amino acid
      substitution in the NKX2-1 protein. In this study, we have examined 102
      additional Chinese and 70 Caucasian patients and 194 Chinese and 60 Caucasian
      unselected, unrelated, subjects as controls. The relevance of the DNA changes
      detected in NKX2-1 by direct sequencing were evaluated using bioinformatics,
      reporter and binding-assays, mouse neurosphere culture, immunohistochemistry and
      immunofluorescence techniques. Met3Leu and Pro48Pro were identified in 2
      Caucasian and 1 Chinese patients respectively. In vitro analysis showed that
      Met3Leu reduced the activity of the RET promoter by 100% in the presence of the
      wild-type or HSCR-associated RET promoter SNP alleles. The apparent binding
      affinity of the NKX2-1 mutated protein was not decreased. The Met3Leu mutation
      may affect the interaction of NKX2-1 with its protein partners. The absence of
      NKX2-1 expression in mouse but not in human gut suggests that the role of NKX2-1
      in gut development differs between the two species. NKX2-1 mutations could
      contribute to HSCR by affecting RET expression through defective interactions
      with other transcription factors.

PMID- 18081919
TI  - Genetic influences on disordered eating behaviour are largely independent of body
      mass index.
AB  - OBJECTIVE: Prior studies suggest eating disorders and related characteristics are
      moderately to substantially heritable. We are interested in identifying the genes
      underlying disordered eating behaviour (DEB), and want to know how much of the
      genetic influence underlying DEB is attributable to genetic influences on body
      mass index (BMI). METHOD: Bivariate analyses were performed, in adolescent twins
      and siblings, to estimate the genetic and environmental contributions for DEB,
      BMI, and their overlap. RESULTS: Shared genetic risk factors explained the
      overlap between BMI and DEB (genetic correlation was 0.43 in women, 0.51 in men).
      DEB was highly heritable in women (a(2) = 0.65; a(2) independent of BMI = 0.53)
      and moderately heritable in men (a(2) = 0.39; a(2) independent of BMI = 0.29).
      BMI was highly heritable in both men (a(2) = 0.76) and women (a(2) = 0.80).
      CONCLUSION: The entire correlation between DEB and BMI was explained by shared
      genetic risk, but the majority of genetic influences on DEB were due to genetic
      effects independent of BMI.

PMID- 18081920
TI  - Complaints of stress in young soldiers strongly predispose to psychiatric
      morbidity and mortality: Danish national cohort study with 10-year follow-up.
AB  - OBJECTIVE: Serving military can be regarded as exposure to a moderate enforced
      stressor independent of other vulnerability factors. The aims of this study were
      i) to explore psychiatric morbidity and mortality during 10 years of follow-up in
      a cohort of healthy adolescent Danish conscripts and ii) to investigate whether
      stress-related disorders precede other psychiatric disorders. METHOD: Controlled
      national cohort study on all psychiatric hospital contacts in young men referred
      to the Military Psychiatric Department (MPD) with 10 years of follow-up. RESULTS:
      During the follow-up period, 24% of conscripts seen at the MPD were diagnosed
      with a psychiatric disorder compared with 4% in the control cohort. Almost all
      diagnostic categories were over-represented but especially psychotic disorders.
      Mortality was substantially increased. Of subjects initially diagnosed with
      stress-related disorders at the MPD, 20% later on developed psychopathology.
      CONCLUSION: Young healthy men complaining of mental distress following a stressor
      are strongly disposed to psychiatric morbidity and mortality. The study suggests
      that stress-related disorders often precede more severe psychopathology.

PMID- 18081921
TI  - Illicit drug use in patients with psychotic disorders compared with that in the
      general population: a cross-sectional study.
AB  - OBJECTIVE: Prevalence estimates of illicit drug use in psychotic disorders vary
      between studies, and only a few studies compared prevalence estimates with those
      in the general population. METHOD: Cross-sectional study comparing 148 stable
      phase patients with schizophrenia or bipolar disorder with 329 representative
      general citizens of Oslo. A total of 849 patients from the same hospital
      department in the same time period constituted a patient reference group.
      RESULTS: Lifetime illicit drug use was 44% higher (P < 0.001) in study patients
      than in the general population sample; while lifetime use of amphetamine/cocaine
      was 160% higher (P < 0.001). No differences were found between user groups for
      sociodemographic characteristics. CONCLUSION: Patients with psychotic disorders
      in stable phase had a markedly higher lifetime use of any illicit substance,
      especially amphetamine/cocaine, than the general population. They also seemed to
      use drugs more periodically. The same sociodemographic characteristics were
      associated with increased illicit drug use in both groups.

PMID- 18081922
TI  - Premorbid adjustment, symptom development and quality of life in first episode
      psychosis: a systematic review and critical reappraisal.
AB  - OBJECTIVE: To systematically review the relationship of premorbid adjustment to
      symptomatology in first episode psychosis (FEP), taking into account the
      influence of duration of untreated psychosis (DUP). METHOD: Electronic databases
      were searched to identify relevant studies. RESULTS: A variety of approaches to
      the reporting of premorbid adjustment were identified. There was no significant
      association between premorbid adjustment and DUP, supporting the proposition that
      they are independent constructs. The effect of premorbid adjustment upon positive
      symptomatology was negligible. Premorbid adjustment had a modest effect upon
      negative symptoms and quality of life, increasing over duration of follow-up.
      CONCLUSION: Premorbid adjustment remains a valid construct in the study of FEP.
      Both premorbid adjustment and DUP confer independent effects on aspects of
      symptomatology in FEP. Results for premorbid adjustment are similar to previous
      findings in more chronic samples. The potential for conceptualizing premorbid
      functioning by developmental, academic/social and typological approaches is
      currently underexploited.

PMID- 18081923
TI  - Validity and reliability of the Spanish versions of the Bech-Rafaelsen's mania
      and melancholia scales for bipolar disorders.
AB  - OBJECTIVE: To assess classical psychometric properties of the Spanish versions of
      the Bech-Rafaelsen's mania (MAS) and melancholia (MES) scales. METHOD:
      Observational, prospective, and multicentric study in bipolar out-patients.
      Convergent validity was assessed against the Young Mania Rating Scale and the
      Montgomery-Asberg Depression Rating Scale. Discriminant validity, reliability,
      and sensitivity to change, were also assessed. RESULTS: One hundred and thirteen
      bipolar patients with a manic episode and 102 bipolar patients with a depressive
      episode were included. Both the MAS and the MES showed appropriate convergent
      validity (r > 0.90), discriminant validity (P < 0.0001), internal consistency
      (Cronbach's alpha >0.80), test-retest reliability [intraclass correlation
      coefficient (ICC) = 0.69 for the MAS and 0.94 for the MES], inter-rater
      reliability (ICC > 0.80), and sensitivity to change at 4 weeks since inception (P
      < 0.0001; within-group effect size >or=1.8). CONCLUSION: The Spanish versions of
      both scales present appropriate psychometric estimates in bipolar patients
      treated in ambulatory care.

PMID- 18081924
TI  - Elevated cytokine expression in the orbitofrontal cortex of victims of suicide.
AB  - OBJECTIVE: Based on the reported association between cytokines with depression
      and suicide, and evidence of increased markers of inflammation in the brain of
      suicide victims, the present study examined the expression of cytokines in the
      orbitofrontal cortex of suicide victims. METHOD: In a postmortem sample obtained
      from the Brodman area 11 of suicides (n = 34) and controls (n = 17), real-time RT
      PCR was used to compare the expression of mRNA species for tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-1 beta, 4, 5, 6, and 13. RESULTS: Increased
      expression of IL-4 was found in women suicide victims and IL-13 in men suicide
      victims. Elevated but not significant cytokine expression was also observed for
      TNF-alpha in women suicide victims. CONCLUSION: To our knowledge, these results
      provide the first evidence of the presence of mRNA transcripts of type 2 T-helper
      cytokines in the human orbitofrontal cortex and their increased expression in the
      brain of suicides.

PMID- 18081925
TI  - Differential resistance to cell entry by porcine endogenous retrovirus subgroup A
      in rodent species.
AB  - BACKGROUND: The risk of zoonotic infection by porcine endogenous retroviruses
      (PERV) has been highlighted in the context of pig-to-human xenotransplantation.
      The use of receptors for cell entry often determines the host range of
      retroviruses. A human-tropic PERV subgroup, PERV-A, can enter human cells through
      either of two homologous multitransmembrane proteins, huPAR-1 and huPAR-2. Here,
      we characterised human PARs and their homologues in the PERV-A resistant rodent
      species, mouse and rat (muPAR and ratPAR, respectively). RESULTS: Upon exogenous
      expression in PERV-A resistant cells, human and rat PARs, but not muPAR,
      conferred PERV-A sensitivity. Exogenously expressed ratPAR binds PERV-A Env and
      allows PERV-A infection with equivalent efficiency to that of huPAR-1. Endogenous
      ratPAR expression in rat cell lines appeared to be too low for PERV-A infection.
      In contrast, the presence of Pro at position 109 in muPAR was identified to be
      the determinant for PERV-A resistance. Pro109. was shown to be located in the
      second extracellular loop (ECL2) and affected PERV-A Env binding to PAR
      molecules. CONCLUSION: The basis of resistance to PERV-A infection in two rodent
      species is different. Identification of a single a.a. mutation in muPAR, which is
      responsible for mouse cell resistance to PERV-A highlighted the importance of ECL
      2 for the viral receptor function.

PMID- 18081927
TI  - Assessment of three-dimensional set-up errors in conventional head and neck
      radiotherapy using electronic portal imaging device.
AB  - BACKGROUND: Set-up errors are an inherent part of radiation treatment process.
      Coverage of target volume is a direct function of set-up margins, which should be
      optimized to prevent inadvertent irradiation of adjacent normal tissues. The aim
      of this study was to evaluate three-dimensional (3D) set-up errors and propose
      optimum margins for target volume coverage in head and neck radiotherapy.
      METHODS: The dataset consisted of 93 pairs of orthogonal simulator and
      corresponding portal images on which 558 point positions were measured to
      calculate translational displacement in 25 patients undergoing conventional head
      and neck radiotherapy with antero-lateral wedge pair technique. Mean
      displacements, population systematic (Sigma) and random (sigma) errors and 3D
      vector of displacement was calculated. Set-up margins were calculated using
      published margin recipes. RESULTS: The mean displacement in antero-posterior
      (AP), medio-lateral (ML) and supero-inferior (SI) direction was -0.25 mm (-6.50
      to +7.70 mm), -0.48 mm (-5.50 to +7.80 mm) and +0.45 mm (-7.30 to +7.40 mm)
      respectively. Ninety three percent of the displacements were within 5 mm in all
      three cardinal directions. Population systematic (Sigma) and random errors
      (sigma) were 0.96, 0.98 and 1.20 mm and 1.94, 1.97 and 2.48 mm in AP, ML and SI
      direction respectively. The mean 3D vector of displacement was 3.84 cm. Using van
      Herk's formula, the clinical target volume to planning target volume margins were
      3.76, 3.83 and 4.74 mm in AP, ML and SI direction respectively. CONCLUSION: The
      present study report compares well with published set-up error data relevant to
      head and neck radiotherapy practice. The set-up margins were <5 mm in all
      directions. Caution is warranted against adopting generic margin recipes as
      different margin generating recipes lead to a different probability of target
      volume coverage.

PMID- 18081926
TI  - Role of the long cytoplasmic domain of the SIV Env glycoprotein in early and late
      stages of infection.
AB  - BACKGROUND: The Env glycoproteins of retroviruses play an important role in the
      initial steps of infection involving the binding to cell surface receptors and
      entry by membrane fusion. The Env glycoprotein also plays an important role in
      viral assembly at a late step of infection. Although the Env glycoprotein
      interacts with viral matrix proteins and cellular proteins associated with lipid
      rafts, its possible role during the early replication events remains unclear.
      Truncation of the cytoplasmic tail (CT) of the Env glycoprotein is acquired by
      SIV in the course of adaptation to human cells, and is known to be a determinant
      of SIV pathogenicity. RESULTS: We compared SIV viruses with full length or
      truncated (T) Env glycoproteins to analyze possible differences in entry and post
      entry events, and assembly of virions. We observed that early steps in
      replication of SIV with full length or T Env were similar in dividing and non
      dividing cells. However, the proviral DNA of the pathogenic virus clone SIVmac239
      with full length Env was imported to the nucleus about 20-fold more efficiently
      than proviral DNA of SIVmac239T with T Env, and 100-fold more efficiently than an
      SIVmac18T variant with a single mutation A239T in the SU subunit and with a
      truncated cytoplasmic tail (CT). In contrast, proviral DNA of SIVmac18 with a
      full length CT and with a single mutation A239T in the SU subunit was imported to
      the nucleus about 50-fold more efficiently than SIVmac18T. SIV particles with
      full length Env were released from rhesus monkey PBMC, whereas a restriction of
      release of virus particles was observed from human 293T, CEMx174, HUT78 or
      macrophages. In contrast, SIV with T Envs were able to overcome the inhibition of
      release in human HUT78, CEMx174, 293T or growth-arrested CEMx174 cells and
      macrophages resulting in production of infectious particles. We found that the
      long CT of the Env glycoprotein was required for association of Env with lipid
      rafts. An Env mutant C787S which eliminated palmitoylation did not abolish Env
      incorporation into lipid rafts, but prevented virus assembly. CONCLUSION: The
      results indicate that the long cytoplasmic tail of the SIV Env glycoprotein may
      govern post-entry replication events and plays a role in the assembly process.

PMID- 18081928
TI  - The E3 ubiquitin ligase skp2 regulates neural differentiation independent from
      the cell cycle.
AB  - BACKGROUND: The SCFskp2 complex is an E3 ubiquitin ligase that is known to target
      a number of cell cycle regulators, including cyclin-dependent kinase inhibitors,
      for proteolysis. While its role in regulation of cell division has been well
      documented, additional functions in differentiation, including in the nervous
      system, have not been investigated. RESULTS: Using Xenopus as a model system,
      here we demonstrate that skp2 has an additional role in regulation of
      differentiation of primary neurons, the first neurons to differentiate in the
      neural plate. Xenopus skp2 shows a dynamic expression pattern in early embryonic
      neural tissue and depletion of skp2 results in generation of extra primary
      neurons. In contrast, over-expression of skp2 inhibits neurogenesis in a manner
      dependent on its ability to act as part of the SCFskp2 complex. Moreover,
      inhibition of neurogenesis by skp2 occurs upstream of the proneural gene encoding
      NeuroD and prior to cell cycle exit. We have previously demonstrated that the
      Xenopus cyclin dependent kinase inhibitor Xic1 is essential for primary
      neurogenesis at an early stage, and before these cells exit the cell cycle. We
      show that SCFskp2 degrades Xic1 in embryos and this contributes to the ability of
      skp2 to regulate neurogenesis. CONCLUSION: We conclude that the SCFskp2 complex
      has functions in the control of neuronal differentiation additional to its role
      in cell cycle regulation. Thus, it is well placed to be a co-ordinating factor
      regulating both cell proliferation and cell differentiation directly.

PMID- 18081929
TI  - Linear scleroderma as a rare cause of enophthalmos: a case report.
AB  - INTRODUCTION: Enophthalmos is an important physical sign which can be easily
      missed. CASE PRESENTATION: A 64-year old female presented with painless and
      progressive shrinking of her right eye. Visual acuity was 6/6 in both eyes. The
      main clinical findings included exophthalmometry readings of 14 mm in the right
      eye and 22 mm in the left eye and a linear scar on her right forehead. This scar
      is a feature of linear scleroderma and called "en coup de sabre". She was
      referred to a dermatologist for further assessment. CONCLUSION: Enophthalmos is
      defined as the relative recession of the globe into the bony orbit and if
      measuring greater than 2 mm can give a noticeable cosmetic deformity. Scleroderma
      is a systemic or localised disease. Linear scleroderma has the following features
      localised fibrosis of the skin, blood vessels, subcutaneous fat, muscle and
      sometimes bone. Histology shows an inflammatory and a sclerotic phase. Ophthalmic
      effects include enophthalmos, lash loss, lid induration or tightening and
      periorbital oedema.

PMID- 18081931
TI  - Leiomyosarcoma of the skin with osteoclast-like giant cells: a case report.
AB  - INTRODUCTION: Osteoclast-like giant cells have been noted in various malignant
      tumors, such as, carcinomas of pancreas and liver and leiomyosarcomas of non
      cutaneous locations, such as, uterus and rectum. We were unable to find any
      reported case of a leiomyosarcoma of the skin where osteoclast-like giant cells
      were present in the tumor. CASE PRESENTATION: We report a case of a 59-year-old
      woman with a cutaneous leiomyosarcoma associated with osteoclast-like giant cells
      arising from the subcutaneous artery of the leg. The nature of the giant cells is
      discussed in light of the findings from the immunostaining as well as survey of
      the literature. CONCLUSION: A rare case of cutaneous leiomyosarcoma with
      osteoclast-like giant cells is reported. The giant cells in the tumor appear to
      be reactive histiocytic cells.

PMID- 18081930
TI  - Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured
      ions.
AB  - INTRODUCTION: Metabolic acidosis during hemorrhagic shock is common and
      conventionally considered to be due to hyperlactatemia. There is increasing
      awareness, however, that other nonlactate, unmeasured anions contribute to this
      type of acidosis. METHODS: Eleven anesthetized dogs were hemorrhaged to a mean
      arterial pressure of 45 mm Hg and were kept at this level until a metabolic
      oxygen debt of 120 mLO2/kg body weight had evolved. Blood pH, partial pressure of
      carbon dioxide, and concentrations of sodium, potassium, magnesium, calcium,
      chloride, lactate, albumin, and phosphate were measured at baseline, in shock,
      and during 3 hours post-therapy. Strong ion difference and the amount of weak
      plasma acid were calculated. To detect the presence of unmeasured anions, anion
      gap and strong ion gap were determined. Capillary electrophoresis was used to
      identify potential contributors to unmeasured anions. RESULTS: During induction
      of shock, pH decreased significantly from 7.41 to 7.19. The transient increase in
      lactate concentration from 1.5 to 5.5 mEq/L during shock was not sufficient to
      explain the transient increases in anion gap (+11.0 mEq/L) and strong ion gap
      (+7.1 mEq/L), suggesting that substantial amounts of unmeasured anions must have
      been generated. Capillary electrophoresis revealed increases in serum
      concentration of acetate (2.2 mEq/L), citrate (2.2 mEq/L), alpha-ketoglutarate
      (35.3 microEq/L), fumarate (6.2 microEq/L), sulfate (0.1 mEq/L), and urate (55.9
      microEq/L) after shock induction. CONCLUSION: Large amounts of unmeasured anions
      were generated after hemorrhage in this highly standardized model of hemorrhagic
      shock. Capillary electrophoresis suggested that the hitherto unmeasured anions
      citrate and acetate, but not sulfate, contributed significantly to the changes in
      strong ion gap associated with induction of shock.

PMID- 18081932
TI  - Denoising inferred functional association networks obtained by gene fusion
      analysis.
AB  - BACKGROUND: Gene fusion detection - also known as the 'Rosetta Stone' method -
      involves the identification of fused composite genes in a set of reference
      genomes, which indicates potential interactions between its un-fused counterpart
      genes in query genomes. The precision of this method typically improves with an
      ever-increasing number of reference genomes. RESULTS: In order to explore the
      usefulness and scope of this approach for protein interaction prediction and
      generate a high-quality, non-redundant set of interacting pairs of proteins
      across a wide taxonomic range, we have exhaustively performed gene fusion
      analysis for 184 genomes using an efficient variant of a previously developed
      protocol. By analyzing interaction graphs and applying a threshold that limits
      the maximum number of possible interactions within the largest graph components,
      we show that we can reduce the number of implausible interactions due to the
      detection of promiscuous domains. With this generally applicable approach, we
      generate a robust set of over 2 million distinct and testable interactions
      encompassing 696,894 proteins in 184 species or strains, most of which have never
      been the subject of high-throughput experimental proteomics. We investigate the
      cumulative effect of increasing numbers of genomes on the fidelity and quantity
      of predictions, and show that, for large numbers of genomes, predictions do not
      become saturated but continue to grow linearly, for the majority of the species.
      We also examine the percentage of component (and composite) proteins with
      relation to the number of genes and further validate the functional categories
      that are highly represented in this robust set of detected genome-wide
      interactions. CONCLUSION: We illustrate the phylogenetic and functional diversity
      of gene fusion events across genomes, and their usefulness for accurate
      prediction of protein interaction and function.

PMID- 18081933
TI  - Genome-wide expression patterns of invasion front, inner tumor mass and
      surrounding normal epithelium of colorectal tumors.
AB  - Colorectal tumors have characteristic genome-wide expression patterns that allow
      their distinction from normal colon epithelia and facilitate clinical prognosis.
      The expression heterogeneity within a primary colorectal tumor has not been
      studied on a genome scale yet. Here we investigated three compartments of
      colorectal tumors, the invasion front, the inner tumor mass, and surrounding
      normal epithelial tissue by microdissection and microarray-based expression
      profiling. In both tumor compartments many genes were differentially expressed
      when compared to normal epithelium. The sets of significantly deregulated genes
      in both compartments overlapped to a large extent and revealed various
      interesting known and novel pathways that could have contributed to
      tumorigenesis. Cells from the invasion front and inner tumor mass, however, did
      not show significant differences in their expression profile, neither on the
      single gene level nor on the pathway level. Instead, gene expression differences
      between individuals are more pronounced as all patient-matched tumor samples
      clustered in close proximity to each other. With respect to invasion front and
      inner tumor mass we conclude that the specific tumor cell micro-environment does
      not have a strong influence on expression patterns: largely similar genome-wide
      expression programs operate in the invasion front and interior compartment of a
      colorectal tumor.

PMID- 18081934
TI  - An analysis of the epitope knowledge related to Mycobacteria.
AB  - BACKGROUND: Tuberculosis, caused by the bacterium Mycobacterium tuberculosis,
      remains a leading cause of infectious disease morbidity and mortality, and is
      responsible for more than 2 million deaths a year. Reports about extremely drug
      resistant (XDR) strains have further heightened the sense of urgency for the
      development of novel strategies to prevent and treat TB. Detailed knowledge of
      the epitopes recognized by immune responses can aid in vaccine and diagnostics
      development, and provides important tools for basic research. The analysis of
      epitope data corresponding to M. tuberculosis can also identify gaps in our
      knowledge, and suggest potential areas for further research and discovery. The
      Immune Epitope Database (IEDB) is compiled mainly from literature sources, and
      describes a broad array of source organisms, including M. tuberculosis and other
      Mycobacterial species. DESCRIPTION: A comprehensive analysis of IEDB data
      regarding the genus Mycobacteria was performed. The distribution of antibody/B
      cell and T cell epitopes was analyzed in terms of their associated recognition
      cell type effector function and chemical properties. The various species, strains
      and proteins which the epitope were derived, were also examined. Additional
      variables considered were the host in which the epitopes were defined, the
      specific TB disease state associated with epitope recognition, and the HLA
      associated with disease susceptibility and endemic regions were also scrutinized.
      Finally, based on these results, standardized reference datasets of mycobacterial
      epitopes were generated. CONCLUSION: All current TB-related epitope data was
      cataloged for the first time from the published literature. The resulting
      inventory of more than a thousand different epitopes should prove a useful tool
      for the broad scientific community. Knowledge gaps specific to TB epitope data
      were also identified. In summary, few non-peptidic or post-translationally
      modified epitopes have been defined. Most importantly epitopes have apparently
      been defined from only 7% of all ORFs, and the top 30 most frequently studied
      protein antigens contain 65% of the epitopes, leaving the majority of M.
      tuberculosis genome unexplored. A lack of information related to the specific
      strains from which epitopes are derived is also evident. Finally, the generation
      of reference lists of mycobacterial epitopes should also facilitate future
      vaccine and diagnostic research.

PMID- 18081935
TI  - Orthologs of the small RPB8 subunit of the eukaryotic RNA polymerases are
      conserved in hyperthermophilic Crenarchaeota and "Korarchaeota".
AB  - Although most of the key components of the transcription apparatus, and in
      particular, RNA polymerase (RNAP) subunits, are conserved between archaea and
      eukaryotes, no archaeal homologs of the small RPB8 subunit of eukaryotic RNAP
      have been detected. We report that orthologs of RPB8 are encoded in all sequenced
      genomes of hyperthermophilic Crenarchaeota and a recently sequenced "korarchaeal"
      genome, but not in Euryarchaeota or the mesophilic crenarchaeon Cenarchaeum
      symbiosum. These findings suggest that all 12 core subunits of eukaryotic RNAPs
      were already present in the last common ancestor of the extant archaea.

PMID- 18081936
TI  - Ubiquitination of HTLV-I Tax in response to DNA damage regulates nuclear complex
      formation and nuclear export.
AB  - BACKGROUND: The HTLV-I oncoprotein, Tax, is a pleiotropic protein whose activity
      is partially regulated by its ability to interact with, and perturb the functions
      of, numerous cellular proteins. Tax is predominantly a nuclear protein that
      localizes to nuclear foci known as Tax Speckled Structures (TSS). We recently
      reported that the localization of Tax and its interactions with cellular proteins
      are altered in response to various forms of genotoxic and cellular stress. The
      level of cytoplasmic Tax increases in response to stress and this relocalization
      depends upon the interaction of Tax with CRM1. Cellular pathways and signals that
      regulate the subcellular localization of Tax remain to be determined. However,
      post-translational modifications including sumoylation and ubiquitination are
      known to influence the subcellular localization of Tax and its interactions with
      cellular proteins. The sumoylated form of Tax exists predominantly in the nucleus
      while ubiquitinated Tax exists predominantly in the cytoplasm. Therefore, we
      hypothesized that post-translational modifications of Tax that occur in response
      to DNA damage regulate the localization of Tax and its interactions with cellular
      proteins. RESULTS: We found a significant increase in mono-ubiquitination of Tax
      in response to UV irradiation. Mutation of specific lysine residues (K280 and
      K284) within Tax inhibited DNA damage-induced ubiquitination. In contrast to wild
      type Tax, which undergoes transient nucleocytoplasmic shuttling in response to
      DNA damage, the K280 and K284 mutants were retained in nuclear foci following UV
      irradiation and remained co-localized with the cellular TSS protein, sc35.
      CONCLUSION: This study demonstrates that the localization of Tax, and its
      interactions with cellular proteins, are dynamic following DNA damage and depend
      on the post-translational modification status of Tax. Specifically, DNA damage
      induces the ubiquitination of Tax at K280 and K284. Ubiquitination of these
      residues facilitates the dissociation of Tax from sc35-containing nuclear foci,
      and stimulates nuclear export of Tax through the CRM1 pathway.

PMID- 18081937
TI  - Incidence of early posterior shoulder dislocation in brachial plexus birth palsy.
AB  - BACKGROUND: Posterior dislocation of the shoulder in brachial plexus birth palsy
      during the first year of life is rare but the incidence increases with age. The
      aim was to calculate the incidence of these lesions in children below one year of
      age. METHODS: The incidence of brachial plexus birth lesion and occurrence of
      posterior shoulder dislocation was calculated based on a prospective follow up of
      all brachial plexus patients at an age below one in Malmo municipality, Sweden,
      2000-2005. RESULTS: The incidence of brachial plexus birth palsy was 3.8/1000
      living infants and year with a corresponding incidence of posterior shoulder
      dislocation (history, clinical examination and x-ray) during the first year of
      0.28/1000 living infants and year, i.e. 7.3% of all brachial plexus birth
      palsies. CONCLUSION: All children with a brachial plexus birth lesion (incidence
      3.8 per thousand) should be screened, above the assessment of neurological
      recovery, during the first year of life for posterior dislocation of the shoulder
      (incidence 0.28 per thousand) since such a condition may occur in 7% of children
      with a brachial plexus birth lesion.

PMID- 18081938
TI  - Depression and quality of life in cancer survivors: is there a relationship with
      physical activity?
AB  - BACKGROUND: Evidence is growing on the benefit of physical activity to improve
      well-being following a cancer diagnosis. This study examined changes in physical
      activity from pre to post diagnosis and explored this relationship with quality
      of life and depression. METHODS: Participants were recruited by posters and by
      letter of invitation. The questionnaire was completed by 59 prostate and 32
      breast cancer survivors. RESULTS: Physical activity decreased by 72 minutes per
      week from pre to post diagnosis, although 20.9% reported having increased
      activity post diagnosis. Over 30% were considered depressed. Breast cancer
      participants who increased physical activity post diagnosis reported higher
      scores for Physical Wellbeing subscale (26 versus 21; F[1,29] = 5.19, p < .03),
      Emotional Wellbeing subscale (22 versus 19; F[1,30] = 4.57, p < .04) and
      Functional Wellbeing subscale (26 versus 19; F[1,30] = 9.03, p < .001). A greater
      proportion of participants taking part in no physical activity were depressed
      (55.6%; chi2 = 6.83, p < .04). CONCLUSION: Over 25% of participants identified
      with emotional and/or well being problems, and more than half reported
      insufficient physical activity to yield benefits. Future research needs to gain a
      better understanding of why cancer survivors decrease their physical activity
      following a cancer diagnosis and what is necessary for them in order to retain or
      increase their physical activity.

PMID- 18081940
TI  - Aspirin and reproductive outcomes.
AB  - In the late 1980s and early 1990s, researchers hypothesized that aspirin could be
      used to prevent or delay the onset of preeclampsia. This hypothesis was tested in
      numerous trials which showed limited, but positive results. Subsequently, aspirin
      has been used in an attempt to improve pregnancy outcomes in women who have both
      antiphospholipid antibodies and a history of recurrent loss, and has also been
      used in an attempt to improve the success of in vitro fertilization. In theory,
      aspirin has both positive and negative effects on reproduction. Aspirin, which
      suppresses cyclooxygenase, has the potential to interfere with implantation, but
      also has the potential to support the maintenance of pregnancy. Aspirin is
      prescribed with increasing frequency to reduce the risk of maternal thrombosis
      and reduce the risk of miscarriage and poor pregnancy outcome. Aspirin alone,
      however, is not considered sufficient to prevent thrombosis and even in women
      with the antiphospholipid syndrome, the question as to whether low-dose aspirin
      improves pregnancy outcomes has not been answered affirmatively. Aspirin has
      potential risks. Aspirin inhibits platelet function and can contribute to
      maternal and fetal bleeding. Aspirin crosses the placenta. Although aspirin has
      not been associated with other congenital anomalies, it has been associated with
      an increased risk of vascular disruptions, particularly gastroschisis and
      possibly premature closure of the ductus arteriosus. Nonetheless, large trials
      demonstrate low-dose aspirin's relative safety and generally positive effects on
      reproductive outcomes.

PMID- 18081941
TI  - Cervical cerclage: a review of the evidence.
AB  - Cervical insufficiency is a difficult and confusing diagnosis. Its diagnostic
      criteria, etiology, and treatment are all debated. Cervical cerclage has been a
      common practice in obstetrics since it was first described by Shirodker and then
      McDonald in the 1950s. Cerclages have been placed because of a patient's
      obstetrical history, physical examination, ultrasound, or a combination of the
      above. However, the data supporting cerclage placement is limited. There has
      never been a prospective, randomized, controlled trial of cerclage versus no
      cerclage in patients with a classic history of cervical insufficiency (multiple
      painless second trimester losses occurring at progressively earlier gestational
      ages). This article attempts to review the relevant studies regarding cerclage
      placement for the treatment of cervical insufficiency. Based on the current
      literature, there is evidence supporting cervical cerclage in the following
      limited circumstances: a history of 3 or more spontaneous preterm births or
      second trimester losses; a high-risk patient with a singleton pregnancy who has a
      short cervix in the second trimester. Because the majority of patients with risk
      factors for preterm birth and second trimester loss (poor obstetric history,
      short cervix) will still deliver at term or near-term, studies on the
      effectiveness of cervical cerclage would need many patients to be powered
      appropriately.

PMID- 18081939
TI  - Polycystic ovary syndrome and oocyte developmental competence.
AB  - Folliculogenesis is a complex process, in which multiple endocrine and
      intraovarian paracrine interactions create a changing intrafollicular
      microenvironment for appropriate oocyte development. Within this
      microenvironment, bidirectional cumulus cell-oocyte signaling governs the gradual
      acquisition of developmental competence by the oocyte, defined as the ability of
      the oocyte to complete meiosis and undergo fertilization, embryogenesis, and term
      development. These regulatory mechanisms of follicle growth, controlled in part
      by the oocyte itself, are susceptible to derangement in polycystic ovary syndrome
      (PCOS), a heterogeneous syndrome characterized by ovarian hyperandrogenism,
      insulin resistance, and paracrine dysregulation of follicle development.
      Consequently, only a subset of PCOS patients experience reduced pregnancy outcome
      after ovarian stimulation for in vitro fertilization. Recent data implicate
      functional associations between endocrine/paracrine abnormalities, metabolic
      dysfunction, and altered oocyte gene expression with impaired oocyte
      developmental competence in women with PCOS. Therefore, an understanding of how
      developmentally relevant endocrine/paracrine factors interact to promote optimal
      oocyte developmental is crucial to identify those PCOS patients who might benefit
      from long-term correction of follicle growth to improve fertility, optimize
      follicular responsiveness to gonadotropin therapy, and enhance pregnancy outcome
      by in vitro fertilization.

PMID- 18081942
TI  - Effect of resveratrol, tyrosol and beta-sitosterol on oxidised low-density
      lipoprotein-stimulated oxidative stress, arachidonic acid release and
      prostaglandin E2 synthesis by RAW 264.7 macrophages.
AB  - Oxidation of LDL is hypothesised as an early and critical event in atherogenesis.
      Oxidised LDL (oxLDL) favour the transformation of macrophages into foam cells, an
      important cell involved in atherosclerosis. Furthermore, oxLDL cause multiple
      changes in macrophage functions. Thus, oxLDL induces certain genes, suppresses
      others and alters cell lipid metabolism. Consumption of a Mediterranean diet is
      associated with a low incidence of atherosclerotic disease, but data about the
      specific dietary constituents involved and mechanisms conferring cardioprotection
      are still sparse. The aim of the present study was to determine the effect of
      representative minor components of wine and olive oil on reactive oxygen species
      and eicosanoid synthesis induced by oxLDL-stimulated macrophages. We observed
      that exposure to non-toxic oxLDL concentrations leads to the production of H2O2
      by RAW 264.7 macrophages and this effect was reverted by apocynin, a NADPH
      oxidase inhibitor. Moreover, oxLDL induced arachidonic acid (AA) release, cyclo
      oxygenase-2 overexpression and subsequent PGE2 release. We observed that
      resveratrol and tyrosol revert H2O2 production induced by oxLDL as well as AA
      release and PGE2 synthesis and that these effects were not as a consequence of
      these compounds interfering with the oxLDL binding to their receptors.
      Interestingly, beta-sitosterol presence enhances these polyphenol actions. Thus,
      we found a synergistic action of polyphenols of olive oil and wine and beta
      sitosterol of olive oil led to the modulation of the effects of oxLDL on
      oxidative stress and PGE2 synthesis.

PMID- 18081943
TI  - Gamma-tocotrienol-induced apoptosis in human gastric cancer SGC-7901 cells is
      associated with a suppression in mitogen-activated protein kinase signalling.
AB  - Tocotrienols have been shown to inhibit proliferation and induce apoptosis in
      cancer cells. However, the molecular mechanisms involved in tocotrienol-induced
      apoptosis are still unclear. In the present study, gamma-tocotrienol induced
      apoptosis in human gastric adenocarcinoma SGC-7901 cell line through down
      regulation of the extracellular signal-regulated kinase (ERK) signalling pathway.
      Furthermore, gamma-tocotrienol-induced apoptosis was accompanied by down
      regulation of Bcl-2, up regulation of Bax, activation of caspase-3, and
      subsequent poly (ADP-ribose) polymerase cleavage. These results indicated that up
      or down regulation of Bcl-2 family proteins play a major role in the initiation
      of gamma-tocotrienol-induced apoptosis as an activator of caspase-3. Gamma
      tocotrienol also down regulated the activation of the Raf-ERK signalling pathway,
      and down regulated c-Myc by decreasing the expressions of Raf-1 and p-ERK1/2
      proteins. The results suggest that key regulators in tocotrienol-induced
      apoptosis may be Bcl-2 families and caspase-3 in SGC-7901 cells through down
      regulation of the Raf-ERK signalling pathway.

PMID- 18081944
TI  - Regulation of angiopoietin-like protein 4/fasting-induced adipose factor
      (Angptl4/FIAF) expression in mouse white adipose tissue and 3T3-L1 adipocytes.
AB  - Angiopoietin-like protein 4 (Angptl4)/FIAF (fasting-induced adipose factor) was
      first identified as a target for PPAR and to be strongly induced in white adipose
      tissue (WAT) by fasting. Here we have examined the regulation of the expression
      and release of this adipokine in mouse WAT and in 3T3-L1 adipocytes. Angptl4/FIAF
      expression was measured by RT-PCR and real-time PCR; plasma Angptl4/FIAF and
      release of the protein in cell culture was determined by western blotting. The
      Angptl4/FIAF gene was expressed in each of the major WAT depots of mice, the mRNA
      level in WAT being similar to the liver and much higher (>50-fold) than skeletal
      muscle. Fasting mice (18 h) resulted in a substantial increase in Angptl4/FIAF
      mRNA in liver and muscle (9.5- and 21-fold, respectively); however, there was no
      effect of fasting on Angptl4/FIAF mRNA in WAT and the plasma level of
      Angptl4/FIAF was unchanged. The Angptl4/FIAF gene was expressed in 3T3-L1
      adipocytes before and after differentiation, the level increasing post
      differentiation; Angptl4/FIAF was released into the culture medium. Insulin,
      leptin, dexamethasone, noradrenaline, TNFalpha and several IL (IL-1beta, IL-6, IL
      10, IL-18) had little effect on Angptl4/FIAF mRNA levels in 3T3-L1 adipocytes.
      However, a major stimulation of Angptl4/FIAF expression was observed with
      rosiglitazone and the inflammatory prostaglandins PGD2 and PGJ2. Angptl4/FIAF
      does not act as an adipose tissue signal of nutritional status, but is markedly
      induced by fasting in liver and skeletal muscle.

PMID- 18081945
TI  - Effect of blueberry feeding on plasma lipids in pigs.
AB  - Two feeding trials were conducted with pigs to determine the effects of blueberry
      supplementation on plasma lipid levels and other indices of cardiovascular
      benefit. In the first trial, where basal diets contained a high level of plant
      based components (70 % soya, oats and barley), supplementation with 1, 2 and 4 %
      blueberries resulted in a decrease in total, LDL- and HDL-cholesterol. The
      greatest reduction was observed in the 2 % blueberry-fed pigs, where total, LDL-
      and HDL-cholesterol were reduced 11.7, 15.1 and 8.3 %, respectively. In the
      second trial where basal diets contained only 20 % (w/w) of soya, oats and
      barley, the lipid-modulating effect of blueberries was attenuated, so that
      supplementation with 1.5 % blueberries reduced total cholesterol by 8 %, which
      occurred only in pigs whose diets had been supplemented with cholesterol (0.08
      %), NaCl (0.11 %) and fructose (9 %). In the first feeding trial, blueberry
      supplementation had no effect on blood platelet activity. Blueberry
      supplementation also had no effect on the susceptibility of leucocyte DNA to
      oxidation in the first trial and no effect on the susceptibility of LDL to
      oxidation in the second trial. Results of these two feeding trials are discussed
      in relation to the effects of basal diet composition on lipid-modulating effects
      of blueberries.

PMID- 18081946
TI  - The level of carbonation of a sugar-sweetened beverage preload affects satiety
      and short-term energy and food intakes.
AB  - The consumption of sugar-sweetened beverages is associated with increased
      incidence of overweight and obesity, and a factor underlying this putative link
      could be the relatively low levels of satiety that may be induced by these
      beverages. Although many sugar-sweetened beverages are carbonated, little
      attention has been given to the potential effects of level of carbonation on
      satiety and subsequent intakes. We hypothesized that increasing the level of
      carbonation in a sugar-sweetened beverage would increase satiety and decrease
      intakes in the short term. Using a randomized, within-subject cross-over design,
      thirty non-obese subjects (fifteen women, fifteen men) participated on three
      occasions, 1 week apart. Following a standard breakfast, subjects consumed a
      beverage preload 10 min before consuming a lunch ad libitum. Preloads were the
      same sugar-sweetened beverage (400 ml, 639 kJ) with three levels of carbonation,
      which were low (1.7 volumes), medium (2.5 volumes) and high (3.7 volumes).
      Satiety was assessed using visual analogue scales and intakes were measured at
      the lunch and for the rest of the day. Compared with the beverage with low
      carbonation, consumption of the beverages with medium and high carbonation led to
      significantly (P < 0.05) higher satiety until lunch, when intakes of food and
      energy were significantly (P < 0.05) lower. There were no significant effects on
      satiety following lunch or on intakes for the rest of the day. This short-term
      study suggests that the level of carbonation may need to be taken into account
      when assessing potential effects of beverages on satiety and intake.

PMID- 18081947
TI  - Antibody-based immunotherapy in high-risk neuroblastoma.
AB  - Although great advances have been made in the treatment of low- and intermediate
      risk neuroblastoma in recent years, the prognosis for advanced disease remains
      poor. Therapies based on monoclonal antibodies that specifically target tumour
      cells have shown promise for treatment of high-risk neuroblastoma. This article
      reviews the use of monoclonal antibodies either as monotherapy or as part of a
      multifaceted treatment approach for advanced neuroblastoma, and explains how
      toxins, cytokines, radioactive isotopes or chemotherapeutic drugs can be
      conjugated to antibodies to enhance their effects. Tumour resistance, the
      development of blocking antibodies, and other problems hindering the
      effectiveness of monoclonal antibodies are also discussed. Future therapies under
      investigation in the area of immunotherapy for neuroblastoma are considered.

PMID- 18081948
TI  - A long-term observational study of the impact of badger removal on herd
      restrictions due to bovine TB in the Irish midlands during 1989--2004.
AB  - An observational study was carried out, using data collected from four areas in
      the Irish midlands, between 1989 and 2004, to critically evaluate the long-term
      effects of proactive badger culling and to provide insights into reactive badger
      culling tuberculosis (TB) prevalence in cattle. Confirmed cattle herd TB
      incidence is the outcome measure used throughout. Relative to reactive culling,
      proactive badger culling was associated with a decrease in incidence in each of
      the 16 years of observation, which encompassed periods of both intensive and less
      intensive badger removal. By 2004, we observed a decrease of 22% [95% confidence
      interval (CI) 15-29, P<0.001] in the entire proactive and 37% (95% CI 25-47,
      P<0.001), in the inner proactive removal areas. The size of the decrease
      increased with time (P=0.055). There was a decrease (constant over time) of at
      least 14% (95% CI 76-97, P=0.013) in incidence in the inner compared to the outer
      control area (herds < or = 2 km, >2 km, from proactive removal area boundaries,
      respectively). Incidence in the outer proactive removal area (herds < 1.6 km from
      the proactive removal boundary) was similar to the inner control area (P=0.890).
      Incidence in the outer control area and total control area, compared to a
      neighbouring area some distance away, increased over the course of the study.
      Differences with the total control area were not statistically significant but
      the outer control area was 11% higher than the neighbouring area by 2004
      (borderline significance P=0.057).

PMID- 18081949
TI  - Tick infestation on roe deer in relation to geographic and remotely sensed
      climatic variables in a tick-borne encephalitis endemic area.
AB  - Roe deer Capreolus capreolus are among the most important feeding hosts for the
      sheep tick Ixodes ricinus, thus contributing to the occurrence of tick-borne
      diseases in Europe. Tick-borne encephalitis (TBE), which is transmitted by co
      feeding of larvae and nymphs on rodents, requires precise climatic conditions to
      occur. We used roe deer as sentinels for potential circulation of TBE virus in
      Northern Italy, by examining the association between tick infestation, occurrence
      of TBE human cases, geographical and climatic parameters. Tick infestation on roe
      deer, and particularly frequency of co-feeding, was clearly associated with the
      geographic location and the autumnal cooling rate. Consistently, TBE occurrence
      in humans was geographically related to co-feeding tick abundance. The
      surveillance of tick infestation on roe deer, combined with remotely sensed
      climatic data, could therefore be used as an inexpensive early risk assessment
      tool of favourable conditions for TBE emergence and persistence in humans.

PMID- 18081950
TI  - Lack of response of INT-407 cells to the presence of non-culturable Campylobacter
      jejuni.
AB  - Many contradictory articles on the infectivity of non-culturable Campylobacter
      jejuni can be found. We studied the effect of non-culturable C. jejuni in an in
      vitro assay. To prevent the potential effect of a few culturable bacteria in the
      non-culturable suspension, INT-407 cells, which mimic the outer cell layer in the
      small intestines, were exposed to culturable C. jejuni suspensions with or
      without non-culturable C. jejuni. The number of bacteria adhering to and/or
      invading INT-407 cells and the IL-8 secretion were measured. No differences were
      found between bacterial suspensions with or without non-culturable C. jejuni
      added. These findings show that non-culturable C. jejuni do not adhere to or
      invade INT-407 cells and do not induce an immune response. As previous studies
      showed a correlation between the used in vitro assays and the effect in vivo, our
      study strongly suggests that culturability is a good indicator of the risk for C.
      jejuni infection.

PMID- 18081951
TI  - Prevalence of RTI/STI agents and HIV infection in symptomatic and asymptomatic
      women attending peripheral health set-ups in Delhi, India.
AB  - The study was carried out in symptomatic and asymptomatic women attending
      peripheral health centres to determine the laboratory prevalence of sexually
      transmitted infection (STI), reproductive tract infection (RTI) and HIV. A total
      of 4090 women in four study groups were subjected to general and speculum
      examination and screened for aetiological agents of RTI/STI by standard
      laboratory techniques. The main complaint was vaginal discharge, singly (11.2%)
      or along with other symptoms (49.0%). Prevalence of RTI/STI/HIV infection was
      36.8%. Agents of RTIs were harboured by 24.3% and that of STIs by 12.5%. HIV
      seroprevalence was very low (0.1%). HSV-2 represented the commonest aetiological
      agent of STIs, suggesting the necessity of including anti-HSV treatment in the
      national syndromic management guidelines. The present study highlights the
      importance of routine RTI/STI screening of antenatal mothers to avoid adverse
      consequences to the unborn child, and periodic surveys to detect the infection
      pattern in symptomatic and asymptomatic women, in order to control HIV infection.

PMID- 18081952
TI  - Precis of Evolution in Four Dimensions.
AB  - In his theory of evolution, Darwin recognized that the conditions of life play a
      role in the generation of hereditary variations, as well as in their selection.
      However, as evolutionary theory was developed further, heredity became identified
      with genetics, and variation was seen in terms of combinations of randomly
      generated gene mutations. We argue that this view is now changing, because it is
      clear that a notion of hereditary variation that is based solely on randomly
      varying genes that are unaffected by developmental conditions is an inadequate
      basis for evolutionary theories. Such a view not only fails to provide satisfying
      explanations of many evolutionary phenomena, it also makes assumptions that are
      not consistent with the data that are emerging from disciplines ranging from
      molecular biology to cultural studies. These data show that the genome is far
      more responsive to the environment than previously thought, and that not all
      transmissible variation is underlain by genetic differences. In Evolution in Four
      Dimensions (2005) we identify four types of inheritance (genetic, epigenetic,
      behavioral, and symbol-based), each of which can provide variations on which
      natural selection will act. Some of these variations arise in response to
      developmental conditions, so there are Lamarckian aspects to evolution. We argue
      that a better insight into evolutionary processes will result from recognizing
      that transmitted variations that are not based on DNA differences have played a
      role. This is particularly true for understanding the evolution of human
      behavior, where all four dimensions of heredity have been important.

PMID- 18081967
TI  - Animal innovation defined and operationalized.
AB  - Innovation is a key component of most definitions of culture and intelligence.
      Additionally, innovations may affect a species' ecology and evolution.
      Nonetheless, conceptual and empirical work on innovation has only recently begun.
      In particular, largely because the existing operational definition (first
      occurrence in a population) requires long-term studies of populations, there has
      been no systematic study of innovation in wild animals. To facilitate such study,
      we have produced a new definition of innovation: Innovation is the process that
      generates in an individual a novel learned behavior that is not simply a
      consequence of social learning or environmental induction. Using this definition,
      we propose a new operational approach for distinguishing innovations in the
      field. The operational criteria employ information from the following sources:
      (1) the behavior's geographic and local prevalence and individual frequency; (2)
      properties of the behavior, such as the social role of the behavior, the context
      in which the behavior is exhibited, and its similarity to other behaviors; (3)
      changes in the occurrence of the behavior over time; and (4) knowledge of
      spontaneous or experimentally induced behavior in captivity. These criteria do
      not require long-term studies at a single site, but information from multiple
      populations of a species will generally be needed. These criteria are
      systematized into a dichotomous key that can be used to assess whether a behavior
      observed in the field is likely to be an innovation.

PMID- 18081987
TI  - Neural mechanism of bradycardiac responses elicited by acupuncture-like
      stimulation to a hind limb in anesthetized rats.
AB  - The effects of acupuncture-like stimulation of a hind limb on heart rate were
      examined in anesthetized rats. An acupuncture needle, having a diameter of either
      160 or 340 microm, was inserted into the skin and underlying muscles at a depth
      of about 5 mm and twisted right and left twice every second for 1 min.
      Stimulation by a needle with a diameter of either 160 or 340 microm produced a
      decrease in heart rate. Severance of the femoral and sciatic nerves ipsilateral
      to the hind-limb stimulation completely abolished the bradycardiac response.
      Also, heart rate was significantly decreased by acupuncture-like stimulation of
      the hind-limb muscles alone, but was not significantly influenced by the
      stimulation of the hind-limb skin alone. The bradycardiac response induced by
      acupuncture-like stimulation was not influenced by bilateral severance of the
      vagal nerves at the cervical level, but was abolished by bilateral stellectomy.
      Acupuncture-like stimulation of the hind limb induced a decrease in the activity
      of the cardiac sympathetic efferent nerve as well as a decrease in heart rate.
      These results indicate that the decrease in heart rate induced by acupuncture
      like stimulation of a hind limb is a reflex response. The afferent pathway is
      composed of hind-limb muscle afferents, and the efferent pathway is composed of
      cardiac sympathetic nerves.

PMID- 18081988
TI  - Cost-effectiveness and budget impact of long-acting risperidone in Portugal: a
      modeling exercise.
AB  - BACKGROUND: Previous analyses have shown that long-acting risperidone (LAR) is
      cost-effective in several Western countries. In Portugal, however, the costs of
      key services are lower. Therefore, available evidence in other countries may have
      limited relevance. OBJECTIVE: To estimate costs and effects of LAR versus a
      conventional depot and a short-acting oral atypical antipsychotic over a 5-year
      period in Portugal. METHODS: An existing discrete event model was adapted to
      reflect the Portuguese healthcare setting, based on expert opinion, clinical,
      epidemiological, and cost data. The model compares three scenarios. In scenario
      1, patients start with a conventional depot; in scenario 2, with LAR; and in
      scenario 3, with oral risperidone. The model simulates individual patient
      histories while taking into account patient characteristics such as risk to
      society and side-effects. Subsequently, the model simulates patient histories in
      terms of outpatient appointments, psychotic episodes, treatment, compliance,
      symptom scores, lack of ability to take care presenting an actual risk, and
      treatment setting. Outcomes were number of psychotic episodes, cumulative symptom
      score and direct medical costs. Univariate sensitivity analyses were carried out.
      RESULTS: Compared to a conventional depot and an oral atypical, LAR was estimated
      to save approximately euro 3603 and euro 4682 per patient (respectively) and
      avoid 0.44 and 0.59 relapses per patient in 5 years. Sensitivity analyses showed
      that the outcome of dominance was only sensitive to estimates about unit costs of
      hospital/institutionalization, potential risk, and to the reduction in symptoms
      by use of atypicals. CONCLUSION: Based on this modeling exercise, it could be
      expected that LAR may be a cost-effective treatment with limited budget impact in
      Portugal. However, further studies are required to test the generalizability of
      the results of the present modeling study to the larger population of Portugal.

PMID- 18081989
TI  - ApoB/A1 and LDL-C/HDL-C and the prediction of cardiovascular risk in statin
      treated patients.
AB  - BACKGROUND: It is generally accepted that low density lipoprotein cholesterol
      (LDL-C) or calculated ratios such as LDL-C to high density lipoprotein
      cholesterol (HDL-C) (LDL-C/HDL-C) are useful predictors of risk of cardiovascular
      disease in the primary as well as in the secondary prevention setting. However,
      there is accumulating evidence that the ratio of the corresponding
      apolipoproteins (apoB/A1) might be superior in some populations. Little is known
      with regard to the prognostic significance of apoB/A1 in patients treated with
      statins according to the guidelines. OBJECTIVE: The present study assesses the
      prognostic value of apoB/A1 in such patients receiving statin therapy. METHODS:
      This study was performed in a population of 593 statin-treated patients with
      known coronary heart disease (CHD). It is a post-hoc analysis of a published
      study on the effect of folic acid on cardiovascular risk. The association of
      lipids and apolipoproteins with cardiovascular events was evaluated using
      univariate and multivariate Cox regression models. RESULTS: The apoB/A1 ratio was
      associated with clinical outcome when corrected for standard risk factors,
      whereas LDL-C/HDL-C was not, which could indicate additional significant
      prognostic value of apoB/A1 over and above this classic lipid ratio. However,
      this additional prognostic value was not confirmed by receiver operating
      characteristic (ROC) curves, which showed no increase in the area under the
      curve. CONCLUSION: In statin-treated patients with known CHD, apoB/A1 is
      positively associated with clinical events, whereas the LDL-C/HDL-C is not, but
      apoB/A1 does not increase the area under the curve.

PMID- 18081990
TI  - Running away to the circus.

PMID- 18081991
TI  - Addressing the caregiving crisis.

PMID- 18081992
TI  - Looking back and looking forward.

PMID- 18081993
TI  - Relationship between body mass index and medical care expenditures for North
      Carolina adolescents enrolled in Medicaid in 2004.
AB  - INTRODUCTION: Many studies document that overweight and obese adults have
      substantially higher medical care expenditures than do adults of normal weight,
      but comparable data for children or adolescents are few. This study examines
      patterns of expenditure for medical care and use of medical care services among a
      sample of North Carolina adolescents enrolled in Medicaid, stratified by body
      mass index categories. METHODS: North Carolina public health records, which
      include clinically measured height and weight, were linked to 2004 North Carolina
      Medicaid enrollment records to find adolescents aged 12-18 years whose records
      matched. We then examined all paid claims for 2004 of the 3528 adolescents whose
      records matched. Total expenditures by sex and race, hospital costs, physician
      costs, and prescription drug costs were tabulated and stratified by body mass
      index. We also examined, by body mass index, the percentage of adolescents who
      had a paid claim for selected diagnosed health conditions. RESULTS: Overall, and
      for most demographic and service categories, overweight adolescents and at-risk
      for-overweight adolescents had higher average Medicaid expenditures than did
      normal-weight adolescents. Some of these differences were statistically
      significant. Overweight adolescents were significantly more likely to have a paid
      claim for services related to diabetes, asthma, or other respiratory conditions.
      CONCLUSION: Although based on a small sample, our results suggest that overweight
      has negative health consequences as early as adolescence. Further studies with
      larger samples could help confirm the findings of our study.

PMID- 18081994
TI  - "It is our exercise family": experiences of ethnic older adults in a group-based
      exercise program.
AB  - INTRODUCTION: Enhance Fitness (EF) (formerly the Lifetime Fitness Program) is an
      evidence-based community exercise program for older adults. From 1998 to 2005,
      participation of ethnic older adults increased significantly. However, little
      research is available about what ethnic older adults want or need to continue
      participation in exercise programs. The purpose of this study was to examine how
      physical environment, social environment, and individual biology and behavior
      influence adherence to exercise for ethnic older adults participating in EF.
      METHODS: Six focus groups were conducted with 52 older adults participating in
      EF. Facilitators asked questions about factors that helped participants continue
      exercising in EF. Interviews were audiotaped and transcribed. Transcripts were
      systematically reviewed using content analysis. RESULTS: Focus group participants
      were Chinese (n = 21, 40%), African American (n = 18, 35%), white (n = 10, 19%),
      and Japanese (n = 3, 6%). Mean (SD) age was 76 years (7.4). Participants had, on
      average, participated in EF for 44 months (SD = 37.8). Results revealed four
      themes related to adherence. First, environmental factors that promoted adherence
      were location of the classes, transportation, weather, and the facility. Second,
      design of the exercise program that encouraged adherence included exercise
      content and type of delivery. Third, social support factors that encouraged
      adherence were the socializing and support between class participants and support
      from family, health care providers, and the class instructors. Finally,
      individual factors that encouraged adherence were personality traits and
      feelings, past physical activity experience, health benefits, and mental
      stimulation. CONCLUSION: Findings from this study suggest strategies for
      developing community-based physical activity programs for older adults from
      ethnically diverse communities.

PMID- 18081995
TI  - Factors related to cardiovascular disease risk reduction in midlife and older
      women: a qualitative study.
AB  - INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death for
      women in the United States. A healthy diet and appropriate physical activity can
      help reduce the risk for CVD. However, many women do not follow recommendations
      for these behaviors. In this study, we used qualitative methods to better
      understand knowledge and awareness about CVD in women, perceived threat of CVD,
      barriers to heart-healthy eating and physical activity, and intervention
      strategies for behavior change. METHODS: We conducted four focus groups with 38
      white women aged 40 years or older in Kansas and Arkansas. We also interviewed 25
      Cooperative State Research, Education, and Extension Service agents in those
      states. Environmental audits of grocery stores and the physical environment were
      done in three communities. RESULTS: Most women were aware of the modifiable risk
      factors for CVD. Although they realized they were susceptible, they thought CVD
      was something they could overcome. Common barriers to achieving a heart-healthy
      diet included time and concern about wasting food. Most women had positive
      attitudes toward physical activity and reported exercising in the past, but found
      it difficult to resume when their routine was disrupted. The environmental audits
      suggested that there are opportunities to be physically active and that with the
      exception of fresh fish in Kansas, healthful foods are readily available in local
      food stores. CONCLUSION: Interventions to change behavior should be hands-on,
      have a goal-setting component, and include opportunities for social interaction.
      It is especially important to offer interventions as awareness increases and
      women seek opportunities to build skills to change behavior.

PMID- 18081996
TI  - A comprehensive assessment of the difficulty level and cultural sensitivity of
      online cancer prevention resources for older minority men.
AB  - INTRODUCTION: Older men are at increased risk for prostate cancer. As seniors
      turn to the Internet for cancer information, it is important that the resources
      they locate about lifestyle behaviors and screening are culturally appropriate
      and easy to understand. This study was a comprehensive analysis of prostate
      cancer risk as portrayed on the Internet with assessment of content readability
      and cultural sensitivity. METHODS: We selected Web sites about prostate cancer
      risk and prevention by comparing common sites across three top-rated search
      engines (Google, Yahoo!, and MSN). A total of 70 Web sites on prostate cancer
      containing a Web page on risk factors or prevention or both for racial and ethnic
      populations were included. We assessed readability of one page per Web site using
      Simple Measure of Gobbledygook (SMOG), Flesch-Kincaid (FK), and Flesch Reading
      Ease (FRE) measures. Cultural sensitivity of the Web page was evaluated using the
      Cultural Sensitivity Assessment Tool (CSAT) and questions from a cultural
      sensitivity checklist. RESULTS: Mean readability of Web pages was Grade 12.90
      (high school graduate level) using SMOG and Grade 11.20 according to FK. Mean FRE
      was 45.04 (fairly difficult to read). The mean CSAT score was 2.78 and classified
      as culturally sensitive. Of the 36 Web pages considered culturally sensitive
      (CSAT >2.50), 75% did not portray images of representative racial or ethnic
      individuals as intended readers or as being at high risk for prostate cancer.
      Older adults and seniors were identified as intended readers on 73% of Web pages.
      CONCLUSION: Online cancer resources are targeting appropriate age groups (high
      risk older adults). However, the pages required fairly high-level reading skills
      and had limited cultural sensitivity. These factors make the pages unsuitable for
      diverse Internet users.

PMID- 18081997
TI  - Discussions by elders and adult children about end-of-life preparation and
      preferences.
AB  - INTRODUCTION: In the United States, 73% of deaths occur among people aged 65
      years or older. Although most would prefer to die at home after a short illness,
      most actually die in institutions after prolonged declines. Despite this
      discrepancy, elders and their adult children often do not discuss end-of-life
      preferences. Use of advance directives has not been widespread, and people often
      avoid the subject until a crisis. This project focused on informal family
      communication about end-of-life preparation and preferences, about which little
      is known. METHODS: In May 2006, we conducted in-depth exploratory interviews with
      15 older adults about their end-of-life preparation and preferences and with 15
      younger adults about their parents' end-of-life preparation and preferences. The
      interview included an item rating the depth of discussion. RESULTS: Participants
      in both groups were primarily female and white. Mean age of older adults was 78.6
      years (range, 70-88 years). Mean age of younger adults was 53.1 years (range, 42
      63 years); mean age of their parents was 82.6 years (range, 68-99 years). Nine
      older adults reported discussing end-of-life preparation and preferences with
      their adult children; six had barely discussed the topic at all. Ten younger
      adults reported having talked with their parents about end-of-life preparation
      and preferences; five had not discussed it. Barriers to discussions about end-of
      life preparation and preferences were fear of death, trust in others to make
      decisions, family dynamics, and uncertainty about preferences. Facilitators for
      discussion were acceptance of the reality of death, prior experience with death,
      religion or spirituality, and a desire to help the family. Successful strategies
      included casually approaching the topic and writing down end-of-life preparation
      and preferences. CONCLUSION: Knowing the obstacles to and facilitators for
      discussion can help health care and public health professionals target approaches
      to encouraging elders and their families to discuss end-of-life preparation and
      preferences before a crisis.

PMID- 18081998
TI  - Smoking status as a predictor of hip fracture risk in postmenopausal women of
      northwest Texas.
AB  - INTRODUCTION: The purpose of this study was to determine the effect of cigarette
      smoking on the risk of hip fracture for postmenopausal women living in rural and
      urban areas of Northwest Texas. METHODS: Using an unmatched case-control design,
      we compared postmenopausal women who had recently experienced osteoporotic hip
      fracture with women who had not. Both study groups completed a questionnaire on
      demographic, clinical, and behavioral risk factors for osteoporotic hip fracture.
      We categorized smoking status as never smoked, former smoker, and current smoker.
      Covariates included age, weight, age at menopause, physical activity, estrogen
      replacement, calcium supplementation, and rurality. We used univariate and
      multivariate logistic regressions to test the associations between hip fracture
      and the independent variables of interest. RESULTS: We found an increased risk of
      hip fracture for former smokers (adjusted odds ratio [OR], 2.27; 95% confidence
      interval [CI], 1.22-4.21) and current smokers (adjusted OR, 3.72; 95% CI, 1.59
      8.70). Residence in a rural county (population <100,000) also was associated with
      increased risk (adjusted OR, 2.71; 95% CI, 1.48-4.95). CONCLUSION: Former and
      current smoking increased the risk of hip fracture in this population of
      postmenopausal women.

PMID- 18081999
TI  - Applying the small-area estimation method to estimate a population eligible for
      breast cancer detection services.
AB  - INTRODUCTION: Populations eligible for public health programs are often narrowly
      defined and, therefore, difficult to describe quantitatively, particularly at the
      local level, because of lack of data. This information, however, is vital for
      program planning and evaluation. We demonstrate the application of a statistical
      method using multiple sources of data to generate county estimates of women
      eligible for free breast cancer screening and diagnostic services through
      California's Cancer Detection Programs: Every Woman Counts. METHODS: We used the
      small-area estimation method to determine the proportion of eligible women by
      county and racial/ethnic group. To do so, we included individual and community
      data in a generalized, linear, mixed-effect model. RESULTS: Our method yielded
      widely varied estimated proportions of service-eligible women at the county
      level. In all counties, the estimated proportion of eligible women was higher for
      Hispanics than for whites, blacks, Asian/Pacific Islanders, or American
      Indian/Alaska Natives. Across counties, the estimated proportions of eligible
      Hispanic women varied more than did those of women of other races. CONCLUSION:
      The small-area estimation method is a powerful tool for approximating narrowly
      defined eligible or target populations that are not represented fully in any one
      data source. The variability and reliability of the estimates are measurable and
      meaningful. Public health programs can use this method to estimate the size of
      local populations eligible for, or in need of, preventive health services and
      interventions.

PMID- 18082000
TI  - Dietary practices, dining out behavior, and physical activity correlates of
      weight loss maintenance.
AB  - INTRODUCTION: Loss of excess weight can improve blood lipids, insulin
      sensitivity, and blood pressure. However, data are scant on behavioral strategies
      related to maintenance of weight loss. We examined dietary practices, physical
      activity, and self-efficacy among adults self-reported to be successful at
      maintaining weight loss. METHODS: Using the 2004 Styles survey, a mailed survey
      of U.S. adults aged 18 years or older, we examined behaviors associated with
      weight loss maintenance among people who reported trying to lose weight. We
      analyzed data on number of daily fruit and vegetable servings, minutes per week
      of physical activity, dining out behavior, and confidence in one's ability to
      engage in behavioral strategies. We conducted frequency and multivariable
      logistic regression analyses. RESULTS: More men (35.5%) than women (27.7%) were
      classified as successful weight loss maintainers. Compared with adults who
      reported eating at a fast-food restaurant two or more times per week, adults who
      reported not eating at fast-food restaurants were more successful at weight loss
      maintenance (odds ratio, 1.62; 95% confidence interval, 1.09-2.42). Compared with
      adults who consumed fewer than five fruit and vegetable servings per day and were
      sedentary, adults who consumed fewer than five fruit and vegetable servings per
      day and accrued 420 minutes or more per week of physical activity or consumed
      five or more fruit and vegetable servings and accrued 150 minutes or more per
      week of activity were more successful at weight loss maintenance. CONCLUSION: The
      behavioral strategy of reducing consumption of fast foods could assist people in
      keeping weight off. The combined approach of consuming five or more fruit and
      vegetable servings per day and attaining 150 minutes or more per week of physical
      activity was a common strategy among adults successful at weight loss
      maintenance.

PMID- 18082001
TI  - Pausa para tu Salud: reduction of weight and waistlines by integrating exercise
      breaks into workplace organizational routine.
AB  - INTRODUCTION: Proactive worksite strategies that change the physical or
      sociocultural environment(s) to incorporate obligatory physical activity may be
      necessary to engage sedentary people. This study describes implementation and
      evaluation of an intervention, Pausa para tu Salud (Pause for Your Health), that
      integrated a brief period of group exercise into the workday. METHODS: An
      uncontrolled pretest-post-test study design tested the effects of integrating
      daily 10-minute exercise breaks during paid work time during January 2003 through
      January 2004. A total of 335 Mexican Ministry of Health office workers provided
      baseline data as a part of routine annual clinical screening examinations.
      RESULTS: Baseline mean body mass index and waist circumferences were 27.8 kg/m(2)
      and 87.6 cm for women and 26.6 kg/m(2) and 89.7 cm for men. Complete data were
      available for 271 (80.9%) employees at 1-year follow-up. Two-tailed, paired t
      test comparisons were used. Body mass index decreased by 0.32 kg/m(2) (P = .05),
      and waist circumference by 1.6 cm (P = .0009) overall. The body mass index
      decrease, however, was significant only for men (-0.43 kg/m(2), P = .03).
      Multivariate analyses revealed a significant decrease in diastolic blood pressure
      among women (z = -2.04, P = .042). CONCLUSION: The intervention was associated
      with significant improvements in both measures of body composition. Substantive
      health and organizational benefits may result from integrating brief periods of
      physical activity into the workday if these findings are replicated in randomized
      controlled trials in other worksites.

PMID- 18082002
TI  - Can newly acquired healthy behaviors persist? An analysis of health behavior
      decay.
AB  - INTRODUCTION: We evaluated data from the Coronary Health Improvement Project
      (CHIP) to determine whether improved health behaviors associated with this
      intervention persisted or decayed during 18 months of follow-up. METHODS:
      Participants were 348 volunteers aged 24 to 81 years from the Rockford, Illinois,
      metropolitan area enrolled in CHIP, a 4-week educational course delivered as
      lectures. The intervention taught the importance of making better lifestyle
      choices and improving dietary and physical activity behaviors. Physical activity
      and dietary behaviors were assessed at baseline, and changes in behaviors were
      assessed at 6 weeks and 18 months. Changes were evaluated according to quartile
      groupings of each variable at baseline. RESULTS: No baseline differences were
      found between participants who dropped out and participants who provided data
      through 18 months. Mean changes significantly improved through 6 weeks for each
      of the 21 selected physical activity and dietary behavior variables except
      percentage of daily calories from carbohydrates. Mean changes significantly
      improved through 18 months for each of the 21 variables except calories from
      protein, alcohol, and whole grain servings. The percentage of participants who
      improved their physical or dietary behavior at 6 weeks ranged from 49% for
      percentage of daily calories from carbohydrates (64% at 18 months) to 91% for
      intake of dietary cholesterol per day (84% at 18 months). The level of change
      through 18 months for all variables was significantly influenced by quartile
      groupings at baseline. Physical activity improved significantly through 18 months
      only for participants in the lowest two quartiles of physical activity at
      baseline. Exercise decreased significantly through 18 months for participants in
      the highest quartile of physical activity at baseline. CONCLUSION: During an 18
      month period, participants' physical activity and dietary behaviors improved
      significantly. Even though behavior improvement tended to be greater at 6 weeks,
      most healthy behaviors did not return to baseline levels after 18 months.

PMID- 18082003
TI  - Managed-Medicare health club benefit and reduced health care costs among older
      adults.
AB  - INTRODUCTION: Our study was undertaken to determine the association between use
      of a health plan-sponsored health club benefit by older adults and total health
      care costs over 2 years. METHODS: This retrospective cohort study used
      administrative and claims data from a Medicare Advantage plan. Participants (n =
      4766) were enrolled in the plan for at least 1 year before participating in the
      plan-sponsored health club benefit (Silver Sneakers). Controls (n = 9035) were
      matched to participants by age and sex according to the index date of Silver
      Sneakers enrollment. Multivariate regression models were used to estimate health
      care use and costs and to make subgroup comparisons according to frequency of
      health club visits. RESULTS: Compared with controls, Silver Sneakers participants
      were older and more likely to be male, used more preventive services, and had
      higher total health care costs at baseline. Adjusted total health care costs for
      Silver Sneakers participants and controls did not differ significantly in year 1.
      By year 2, compared with controls, Silver Sneakers participants had significantly
      fewer inpatient admissions (-2.3%, 95% confidence interval, -3.3% to -1.2%; P <
      .001) and lower total health care costs (-$500; 95% confidence interval, -$892 to
      -$106; P = .01]. Silver Sneakers participants who averaged at least two health
      club visits per week over 2 years incurred at least $1252 (95% confidence
      interval, -$1937 to -$567; P < .001) less in health care costs in year 2 than did
      those who visited on average less than once per week. CONCLUSION: Regular use of
      a health club benefit was associated with slower growth in total health care
      costs in the long term but not in the short term. These findings warrant
      additional prospective investigations to determine whether policies to offer
      health club benefits and promote physical activity among older adults can reduce
      increases in health care costs.

PMID- 18082004
TI  - Variation in quality of diabetes care at the levels of patient, physician, and
      clinic.
AB  - INTRODUCTION: We studied variance in glycated hemoglobin (HbA1c) values among
      adults with diabetes to identify variation in quality of diabetes care at the
      levels of patient, physician, and clinic, and to identify which levels contribute
      the most to variation and which variables at each level are related to quality of
      diabetes care. METHODS: Study subjects were 120 primary care physicians and their
      2589 eligible adult patients with diabetes seen at 18 clinics. The dependent
      variable was HbA1c values recorded in clinical databases. Multivariate
      hierarchical models were used to partition variation in HbA1c values across the
      levels of patient, physician, or clinic and to identify significant predictors of
      HbA1c at each level. RESULTS: More than 95% of variance in HbA1c values was
      attributable to the patient level. Much less variance was seen at the physician
      and clinic level. Inclusion of patient and physician covariates did not
      substantially change this pattern of results. Intensification of pharmacotherapy
      (t = -7.40, P < .01) and patient age (t = 2.10, P < .05) were related to
      favorable change in HbA1c. Physician age, physician specialty, number of diabetes
      patients per physician, patient comorbidity, and clinic assignment did not
      predict change in HbA1c value. The overall model with covariates explained 11.8%
      of change in HbA1c value over time. CONCLUSION: These data suggest that most
      variance in HbA1c values is attributable to patient factors, although physicians
      play a major role in some patient factors (e.g., intensification of medication).
      These findings may lead to more effective care-improvement strategies and
      accountability measures.

PMID- 18082006
TI  - Obesity and diabetes in Jordan: findings from the behavioral risk factor
      surveillance system, 2004.
AB  - INTRODUCTION: Chronic diseases are the leading cause of morbidity and mortality
      in Jordan. The Jordanian Ministry of Health, in collaboration with the Centers
      for Disease Control and Prevention, established a behavioral risk factor
      surveillance system to monitor the behavioral risk factors associated with
      chronic diseases. METHODS: We used a multistage sampling design to select
      households from which we then randomly selected and interviewed one adult aged 18
      years or older. A random subsample of the adults interviewed were then invited to
      visit the local health clinic, where we obtained medical measurements, including
      blood lipids (low-density lipoprotein, high-density lipoprotein, and
      triglycerides) and fasting blood glucose. RESULTS: Approximately 9% of the
      participants in the subsample who underwent medical testing reported having been
      diagnosed with diabetes previously, compared with 16.9% diagnosed in our
      laboratory testing. About 12.3% of the participants were glucose intolerant, and
      about 35% were obese. Obesity was significantly associated with diabetes, high
      blood pressure, high cholesterol, and asthma. Compared with adults of normal
      weight, obese adults had an adjusted odds ratio of 3.27 (95% CI, 1.58-6.76) for
      diabetes, 3.69 (95% CI, 2.13-6.39) for high blood pressure, 3.45 (95% CI, 1.68
      7.10) for high cholesterol, and 5.12 (95% CI, 1.53-17.19) for asthma. DISCUSSION:
      Obesity, poor diet, and physical inactivity create a major chronic disease burden
      in Jordan that is likely to increase substantially in the next few years. Our
      findings argue for establishment of a more preventive orientation in health care
      and public health systems in Jordan.

PMID- 18082005
TI  - The effect of advanced access implementation on quality of diabetes care.
AB  - INTRODUCTION: The study analyzes the effect of an advanced access program on
      quality of diabetes care. METHODS: We conducted this study in a medical group of
      240,000 members served by 17 primary care clinics. Seven thousand adult patients
      older than 18 years of age with diabetes were identified from administrative
      databases. Two aspects of advanced access - wait time for appointments and
      continuity of care - were calculated yearly for each patient during 1999 through
      2001. We developed three composite measures of glucose and lipid control -
      process (proportion of patients with appropriate testing rates of hemoglobin A1c
      [HbA1c] and low-density lipoprotein [LDL]), good control (proportion with HbA1c <
      8% and LDL < 130 mg/dL) and excellent control (proportion with HbA1c < 7% and LDL
      < 100 mg/dL) - and assessed them each year for each patient. We used multilevel
      logistic regression to predict the measures in 2000 and 2001 (years during and
      after advanced access implementation) relative to 1999 (year pre-advanced
      access). RESULTS: After implementation of advanced access, wait time decreased
      from 21.6 days to 4.2 days, and continuity improved by 6.5% (both P < .01). The
      percentage of patients with HbA1c < 7% increased from 44.4% to 52.3% and with LDL
      < 100 mg/dL from 29.8% to 38.7%. Increased continuity predicted improved process
      (P = .01), good control (P = .033), and excellent control (P < .001). However,
      wait time did not significantly predict process (P = .62) or quality measures (P
      = .95). CONCLUSION: Measures of the quality of diabetes control improved in the
      year after implementation of advanced access, but better care did not correlate
      with decreased wait time to see a provider. However, improved continuity of care
      predicted improvements in both process and quality of diabetes care.

PMID- 18082007
TI  - Translating a community-based motivational support program to increase physical
      activity among older adults with diabetes at community clinics: a pilot study of
      Physical Activity for a Lifetime of Success (PALS).
AB  - BACKGROUND: Regular physical activity is an important goal for elders with
      chronic health conditions. CONTEXT: This report describes Physical Activity for a
      Lifetime of Success (PALS), an attempt to translate a motivational support
      program for physical activity, Active Choices, for use by a group of diverse, low
      income, community-dwelling elders with diabetes. METHODS: PALS linked physical
      activity assessment and brief counseling by primary care providers with a
      structured referral to a community-based motivational telephone support program
      delivered by older adult volunteers. People with diabetes aged 65 years or older
      who were receiving care at two community clinics were randomized to receive
      either immediate or delayed intervention. The main intended outcome measure was
      physical activity level; the secondary outcome measure was mean hemoglobin A1c.
      CONSEQUENCES: One-third of those offered referral to the PALS program in the
      clinic setting declined. Another 44% subsequently declined enrollment or were
      unreachable by the support center. Only 14 (21%) of those offered referral
      enrolled in the program. Among these 14, the percentage who were sufficiently
      active was higher at follow-up than at enrollment, though not significantly so.
      Using an intent-to-treat analysis, which included all randomized clinic patients,
      we found no significant change in mean hemoglobin A1c for the intervention group
      compared with controls. INTERPRETATION: A community-based referral and support
      program to increase physical activity among elderly, ethnically diverse, low
      income people with diabetes, many of whom are not English-speaking, may be
      thwarted by unforeseen barriers. Those who enroll and participate in the PALS
      program appear to increase their level of physical activity.

PMID- 18082008
TI  - A survey of policies and local ordinances supporting physical activity in Hawaii
      counties.
AB  - BACKGROUND: Features of the built environment that influence physical activity
      behavior characterize Active Community Environments. CONTEXT: Whether Active
      Community Environments policies exist in the state of Hawaii's four counties is
      unknown. The purpose of this study was to provide a baseline assessment of these
      policies in Hawaii. METHODS: A survey assessing policies in six domains (i.e.,
      sidewalks, bike lanes, greenways, recreational facilities, commercial buildings,
      and shared-use paths) was completed by employees of Hawaii planning departments.
      CONSEQUENCES: Honolulu County had the most policies (n = 13), followed by Maui
      County (n = 6), Kauai County (n = 2), and Hawaii County (n = 1). Written policies
      were most prevalent in Honolulu County (n = 15), followed by Kauai County (n =
      14), Hawaii County, (n = 4), and Maui County (n = 3). Sidewalk policies were
      reported for Honolulu County, Maui County (no written policies were found for
      Maui County), and Kauai County. Bike lane and greenway policies were found for
      Honolulu County (reported and written) and Kauai County (written). Recreation
      facility and pedestrian shared-use path policies existed for all counties,
      although only Honolulu and Kauai counties had written policies for commercial
      buildings (Maui County reported having policies). Few policies directly addressed
      physical activity promotion. INTERPRETATION: The most populous county, Honolulu,
      had the most policies in place, although discrepancies existed between reported
      and written policies. This baseline measure of physical activity-related policies
      will help focus efforts of county coalitions to increase opportunities for
      physical activity. Additional policies should be tracked with population behavior
      surveillance.

PMID- 18082009
TI  - Expanding the delivery of clinical preventive services through community
      collaboration: the SPARC model.
AB  - BACKGROUND: Population-based rates of adult vaccinations and cancer screenings
      are low, with less than 40% of older adults up to date with routinely recommended
      prevention services. Delivery rates are lower still in poor and minority
      communities. CONTEXT: During the past 10 years, Sickness Prevention Achieved
      through Regional Collaboration (SPARC), a New England-based nonprofit agency, has
      developed a promising model for increasing community-wide delivery of prevention
      services. However, the SPARC model has not been tested in communities elsewhere.
      In 2006, the Centers for Disease Control and Prevention facilitated a partnership
      between SPARC and the Aging Services division of the Atlanta Regional Commission
      to evaluate the program's replicability. METHODS: SPARC coalitions involving
      local public health agencies, hospitals, social service organizations, and
      advocacy groups were established in two counties of the region, with the Atlanta
      Regional Commission providing regional coordination. Using the SPARC model, the
      coalitions planned, marketed, and implemented community-based activities to
      deliver adult screenings and vaccinations. CONSEQUENCES: During a 3-week pilot
      phase, SPARC clinics were held in central Atlanta at three senior housing
      facilities, a local fire station, and a charter middle school, delivering 353
      prevention services to 314 residents. In Fayette County, 634 people received
      influenza vaccinations on Election Day at SPARC clinics located near 10 polling
      places. INTERPRETATION: The SPARC model provides a practical framework for
      improving the community-wide delivery of disease prevention services. The model
      can galvanize local health services providers to develop successful locally
      tailored interventions, and the approach is applicable in communities outside of
      SPARC's home region.

PMID- 18082010
TI  - Engaging partners to initiate evaluation efforts: tactics used and lessons
      learned from the prevention research centers program.
AB  - BACKGROUND: The Centers for Disease Control and Prevention's (CDC's) Prevention
      Research Centers (PRC) Program underwent a 2-year evaluation planning project
      using a participatory process that allowed perspectives from the national
      community of PRC partners to be expressed and reflected in a national logic
      model. CONTEXT: The PRC Program recognized the challenge in developing a
      feasible, useable, and relevant evaluation process for a large, diverse program.
      To address the challenge, participatory and utilization-focused evaluation models
      were used. METHODS: Four tactics guided the evaluation planning process: 1)
      assessing stakeholders' communication needs and existing communication mechanisms
      and infrastructure; 2) using existing mechanisms and establishing others as
      needed to inform, educate, and request feedback; 3) listening to and using
      feedback received; and 4) obtaining adequate resources and building flexibility
      into the project plan to support multifaceted mechanisms for data collection.
      CONSEQUENCES: Participatory methods resulted in buy-in from stakeholders and the
      development of a national logic model. Benefits included CDC's use of the logic
      model for program planning and development of a national evaluation protocol and
      increased expectations among PRC partners for involvement. Challenges included
      the time, effort, and investment of program resources required for the
      participatory approach and the identification of whom to engage and when to
      engage them for feedback on project decisions. INTERPRETATION: By using a
      participatory and utilization-focused model, program partners positively
      influenced how CDC developed an evaluation plan. The tactics we used can guide
      the involvement of program stakeholders and help with decisions on appropriate
      methods and approaches for engaging partners.

PMID- 18082011
TI  - Depression as a major component of public health for older adults.
AB  - Although public health is often conceptualized only as the prevention of physical
      illness, recent data suggest that mental illnesses are increasingly relevant to
      the mission of disease prevention and health promotion. Projections are that by
      2020, depression will be second only to heart disease in its contribution to the
      global burden of disease as measured by disability-adjusted life years. Also, as
      the population ages, successive cohorts of older adults will account for
      increasingly larger segments of the U.S. population. We present the diagnostic
      criteria for, prevalence of, and risk factors for depressive disorders among
      older adults; the challenges of recognizing and treating depression in this
      population; the cost-effectiveness of relevant public health interventions; and
      the public health implications of these disorders.

PMID- 18082012
TI  - Eating as an automatic behavior.
AB  - The continued growth of the obesity epidemic at a time when obesity is highly
      stigmatizing should make us question the assumption that, given the right
      information and motivation, people can successfully reduce their food intake over
      the long term. An alternative view is that eating is an automatic behavior over
      which the environment has more control than do individuals. Automatic behaviors
      are those that occur without awareness, are initiated without intention, tend to
      continue without control, and operate efficiently or with little effort. The
      concept that eating is an automatic behavior is supported by studies that
      demonstrate the impact of the environmental context and food presentation on
      eating. The amount of food eaten is strongly influenced by factors such as
      portion size, food visibility and salience, and the ease of obtaining food.
      Moreover, people are often unaware of the amount of food they have eaten or of
      the environmental influences on their eating. A revised view of eating as an
      automatic behavior, as opposed to one that humans can self-regulate, has profound
      implications for our response to the obesity epidemic, suggesting that the focus
      should be less on nutrition education and more on shaping the food environment.

PMID- 18082013
TI  - Developing a Telephone Assessment of Physical Activity (TAPA) questionnaire for
      older adults.
AB  - INTRODUCTION: We report on development and preliminary validation of a brief,
      telephone-based measurement tool for assessing physical activity in older adults.
      The Telephone Assessment of Physical Activity (TAPA) questionnaire is based on
      the University of Washington Health Promotion Research Center's Rapid Assessment
      of Physical Activity (RAPA), a written questionnaire. METHODS: The Rapid
      Assessment of Physical Activity questionnaire was modified to permit interviewers
      to administer it as a telephone interview. We retained its scoring levels and
      interpretation. The pilot test of the telephone version assessed the
      questionnaire's ease of administration and construct validity in a community
      based sample of older adults. Spearman rho and kappa statistics were computed for
      comparison with the Rapid Assessment of Physical Activity questionnaire and the
      Community Healthy Activities Model Program for Seniors questionnaire. RESULTS:
      Thirty-four older adults completed the telephone assessment. A Spearman rho of
      0.74 and a kappa statistic of 0.48 were found between TAPA and the written RAPA.
      CONCLUSION: The pilot test demonstrated that the TAPA questionnaire is a
      promising instrument for use as a brief, telephone-based questionnaire for
      assessing physical activity in older adults.

PMID- 18082014
TI  - Design and national dissemination of the StrongWomen Community Strength Training
      Program.
AB  - BACKGROUND: Physical activity is essential for maintaining health and function
      with age, especially among women. Strength training exercises combat weakness and
      frailty and mitigate the development of chronic disease. Community-based programs
      offer accessible opportunities for strength training. PROGRAM DESIGN: The
      StrongWomen Program is an evidence-informed, community-based strength training
      program developed and disseminated to enable women aged 40 or older to maintain
      their strength, function, and independence. The StrongWomen Workshop and
      StrongWomen Tool Kit are the training and implementation tools for the
      StrongWomen Program. Program leaders are trained at the StrongWomen Workshop.
      They receive the StrongWomen Tool Kit and subsequent support to implement the
      program in their communities. DISSEMINATION: Program dissemination began in May
      2003 with a three-part approach: recruiting leaders and forming key partnerships,
      soliciting participant interest and supporting implementation, and promoting
      growth and sustainability. ASSESSMENT: We conducted site visits during the first
      year to assess curriculum adherence. We conducted a telephone survey to collect
      data on program leaders, participants, locations, and logistics. We used a
      database to track workshop locations and program leaders. As of July 2006, 881
      leaders in 43 states were trained; leaders from 35 states had implemented
      programs. CONCLUSION: Evidence-informed strength training programs can be
      successful when dissemination occurs at the community level using trained
      leaders. This research demonstrates that hands-on training, a written manual,
      partnerships with key organizations, and leader support contributed to the
      successful dissemination of the StrongWomen Program. Results presented provide a
      model that may aid the dissemination of other community-based exercise programs.

PMID- 18082015
TI  - Treating depression in older adults: challenges to implementing the
      recommendations of an expert panel.
AB  - Depression is increasingly recognized as a significant public health problem
      among older adults. Because the condition is highly treatable and currently
      undertreated among community-based older adults, late-life depression is an
      appropriate focus for disease prevention programs. We report findings from a
      recent project to review the scientific literature for published reports about
      treatment for depression among community-dwelling older adults and to recommend
      the interventions with proven effectiveness. We also summarize the research
      findings related to each recommended intervention and describe the elements of
      each. To show the difficulties involved in translating research into practice, we
      describe real-world experiences in implementing these evidence-based
      interventions in various community settings. Because depression among older
      people is viewed more and more as a public health problem, we suggest that
      partnerships of providers, patients, and policy makers be forged to overcome
      challenges related to funding, training, and implementing treatments for this
      condition.

PMID- 18082016
TI  - Disaster preparedness and the chronic disease needs of vulnerable older adults.
AB  - About 80% of older adults have at least one chronic condition that makes them
      more vulnerable than healthy people during a disaster. These chronic conditions -
      combined with the physiological, sensory, and cognitive changes experienced as
      part of aging - result in frail older adults having special needs during
      emergencies. Planning and coordination among public health and emergency
      preparedness professionals and professionals who provide services for the aging
      are essential to meet these special needs. Several tools and strategies already
      exist to help prepare these professionals to protect and assist older adults
      during a disaster. These include having professionals from diverse fields work
      and train in coalitions, ensuring that advocates for older adults participate in
      community-wide emergency preparedness, and using community mapping data to
      identify areas where many older adults live.

PMID- 18082017
TI  - Use of colonoscopy and flexible sigmoidoscopy among African Americans and whites
      in a low-income population.

PMID- 18082018
TI  - Wavelet transfer function in the analysis of the influence of a palm grip on
      actual vibrations of an upper limb.
AB  - Algorithms used to determine the vibrations to which hand-tool operators are
      exposed take into account only vibrations measured on a tool. Thus, the
      significant influence of constraints joining the elements of the tool-operator
      system is neglected. This paper attempts to determine the influence of grip on
      vibrations recorded both on the tool and on the limb. The estimation was based on
      the use of the wavelet transfer function, in which the analysis was done by
      filtration with wavelet functions. Signals recorded with the specially designed
      system were utilised in investigations.

PMID- 18082019
TI  - A vibroacoustic model of selected human larynx diseases.
AB  - With the present development of digital registration and methods for processing
      speech it is possible to make effective objective acoustic diagnostics for
      medical purposes. These methods are useful as all pathologies and diseases of the
      human vocal tract influence the quality of a patient's speech signal. Diagnostics
      of the voice organ can be defined as an unambiguous recognition of the current
      condition of a specific voice source. Such recognition is based on an evaluation
      of essential acoustic parameters of the speech signal. This requires creating a
      vibroacoustic model of selected deformations of Polish speech in relation to
      specific human larynx diseases. An analysis of speech and parameter mapping in 29
      dimensional space is reviewed in this study. Speech parameters were extracted in
      time, frequency and cepstral (quefrency) domains resulting in diagrams that
      qualified symptoms and conditions of selected human larynx diseases. The paper
      presents graphically selected human larynx diseases.

PMID- 18082020
TI  - A power transformer as a source of noise.
AB  - This article presents selected results of analyses and simulations carried out as
      part of research performed at the Central Institute of Labor Protection - the
      National Research Institute (CIOP-PIB) in connection with the development of a
      system for active reduction of noise emitted by high power electricity
      transformers. This analysis covers the transformer as a source of noise as well
      as a mathematical description of the phenomenon of radiation of vibroacoustic
      energy through a transformer enclosure modeled as a vibrating rectangular plate.
      Also described is an acoustic model of the transformer in the form of an array of
      loudspeakers.

PMID- 18082021
TI  - Central auditory damage induced by solvent exposure.
AB  - Different studies have demonstrated that solvents may induce auditory damage. It
      has been suggested that part of this damage may be localised in central auditory
      pathways. The present study aimed to investigate possible auditory processing
      disorders related to solvent exposure. Thirty solvent-exposed workers and 30
      gender-, age- and educational level-matched control subjects were selected to
      participate in the study. To select participants, a questionnaire, otoscopy, pure
      tone audiometry and tympanometry were carried out. Filtered speech (FS), random
      gap detection (RGD) and hearing-in-noise tests (HINT) were conducted in the
      selected participants. Both groups of workers presented as a mean normal hearing
      thresholds. However, significant differences between groups were observed for
      RGD, FS and HINT. It is concluded that a possible auditory processing disorder
      may be related to solvent exposure.

PMID- 18082022
TI  - Wroclaw's motorway ring-road--noise protection.
AB  - The 35.4-km stretch of the A8 motorway, i.e., Wroclaw's motorway ring-road
      (WMRR), passes through the north-west part of the city of Wroclaw and 4
      neighbouring districts. Analyses have shown that WMRR will be a source of noise
      in the environment, which may adversely affect large areas. Normative
      environmental protection acts mandate taking all the necessary technical and
      organizational measures to reduce noise generated by the operation of WMRR in
      order to comply with the acoustic environment quality standards. The paper
      presents the research methodology adopted for assessing noise impact and
      designing acoustic barriers, and proposed designs of acoustic barriers which take
      into account the acoustic requirements, technical limitations, urban development,
      and architectural conditions.

PMID- 18082023
TI  - Theoretical predictions and actual hearing threshold levels in workers exposed to
      ultrasonic noise of impulsive character--a pilot study.
AB  - Results of standard pure-tone audiometry (PTA) were collected from 25 workers,
      mainly females, aged 23-58 years, exposed for 2-13 years to ultrasonic noise
      emitted by ultrasonic welders. Hearing tests were completed by evaluation of
      exposure to ultrasonic noise. The subjects' actual audiometric hearing threshold
      levels (HTLs) were compared with theoretical predictions calculated according to
      ISO 1999:1990. In 60% of cases sound pressure levels in the 10-40 kHz 1/3-octave
      bands at workstands exceeded Polish exposure limits for ultrasonic noise. Our
      comparison of predicted and measured HTLs suggests that the ISO 1999:1990 method,
      intended for audible noise, might also make it possible to predict reliably
      permanent hearing loss (in the 2000-6000 Hz frequency range) after exposure to
      ultrasonic noise. No significant progress of hearing impairment (assessed using
      PTA) in the operators of ultrasonic welders was noted. Nevertheless, further
      studies on the hearing status of workers exposed to ultrasonic noise are needed.

PMID- 18082024
TI  - Noise reduction of spiral ducts.
AB  - The paper presents noise reduction (NR) of spiral ducts as a result of
      computational modeling of acoustic wave propagation. Three-dimensional models
      were created with the finite element method in COMSOL Multiphysics version 3.3.
      Nine models of spiral ducts with 1-9 spiral leads were considered. Time-harmonic
      analysis was used to predict NR, which was shown in spectral and interval
      frequency bands. Spiral duct performance can be seen as a comparison of NR before
      and after a change from a circular to a spiral duct.

PMID- 18082025
TI  - Assessing the acoustical climate of underground stations.
AB  - Designing a proper acoustical environment--indispensable to speech recognition-
      in long enclosures is difficult. Although there is some literature on the
      acoustical conditions in underground stations, there is still little information
      about methods that make estimation of correct reverberation conditions possible.
      This paper discusses the assessment of the reverberation conditions of
      underground stations. A comparison of the measurements of reverberation time in
      Warsaw's underground stations with calculated data proves there are divergences
      between measured and calculated early decay time values, especially for long
      source-receiver distances. Rapid speech transmission index values for measured
      stations are also presented.

PMID- 18082026
TI  - Location of noise sources in fluid power machines.
AB  - This paper discusses noise generation mechanisms and techniques for noise
      reduction in fluid power units. Major noise sources in fluid power units can be
      identified with a sound intensity method. It has been proved that components of
      power units with larger sound radiating surfaces such as an electric motor and an
      oil reservoir produce a major part of global noise radiation.

PMID- 18082027
TI  - Accuracy of assessing the level of impulse sound from distant sources.
AB  - Impulse sound events are characterised by ultra high pressures and low
      frequencies. Lower frequency sounds are generally less attenuated over a given
      distance in the atmosphere than higher frequencies. Thus, impulse sounds can be
      heard over greater distances and will be more affected by the environment. To
      calculate a long-term average immission level it is necessary to apply weighting
      factors like the probability of the occurrence of each weather condition during
      the relevant time period. This means that when measuring impulse noise at a long
      distance it is necessary to follow environmental parameters in many points along
      the way sound travels and also to have a database of sound transfer functions in
      the long term. The paper analyses the uncertainty of immission measurement
      results of impulse sound from cladding and destroying explosive materials. The
      influence of environmental conditions on the way sound travels is the focus of
      this paper.

PMID- 18082028
TI  - Decision support system for designing effective noise hazard prevention
      strategies.
AB  - A decision support system for designing effective noise hazard prevention (NHP)
      strategies is proposed. NHP consists of four modules: (a) database, (b) input,
      (c) algorithms, and (d) solution. The user can choose among single-, two-, and
      three-approach solution procedures. Heuristic and genetic algorithms are used to
      determine appropriate noise controls (NCs). From the given noise condition and NC
      budget, NHP recommends a minimum-cost NHP strategy that prevents any worker's
      daily noise exposure from exceeding the permissible level. If the budget is
      insufficient, NHP is able to search for a feasible noise hazard strategy that
      requires a minimum NC budget.

PMID- 18082029
TI  - Effects of dexamethasone on the ultrastructure of alveolar type II cells in young
      rats with lipopolysaccharide-induced acute lung injury.
AB  - OBJECTIVE: Alveolar type II (AT II) cells play a crucial role in the maintenance
      of pulmonary surfactant homeostasis and pulmonary immunity. The effects of
      dexamethasone (Dex) on the ultrastructure of AT II cells after acute lung injury
      remain unknown. This study focused on the ultrastructural changes caused by acute
      lung injury and on the effects of Dex administration on these ultrastructural
      changes in young rats. METHODS: Seventy-two 21-day-old Sprague-Dawley rats were
      randomly divided into control, acute lung injury and Dex-treated groups. Rats in
      the lung injury group were intraperitoneally injected with 4 mg/kg
      lipopolysaccharide (LPS) in order to induce acute lung injury, while the control
      rats were injected with the same amount of normal saline (NS). The Dex-treated
      group was injected first with LPS followed 1 hr later by Dex (5 mg/kg) injection.
      Eight rats in each group were sacrificed 24, 48 and 72 hrs after LPS or NS
      injection. Lung samples were obtained from the lower parts of left lungs and
      fixed with 2.5% glutaraldehyde for transmission electron microscope examination.
      RESULTS: Microvilli of AT II cells disappeared and the number of lamellar bodies
      (LBs) increased in the lung injury group 24 hrs after LPS injection. The ring
      like arrangement of LBs around nuclei was present until 48 hrs after LPS
      injection. By 48 hrs after LPS injection, giant LBs with vacuole-like
      abnormalities appeared. The shape of nuclei became irregular and the border of
      the nuclei became blurred. By 72 hrs after LPS injection, the number of LBs was
      obviously reduced; nucleoli disappeared; and karyolysis occurred in some of the
      nuclei. In contrast, in the Dex-treated group, LBs crowded on one side of AT II
      cells and exocytosis appeared on the same side by 24 hrs after LPS injection. By
      48 hrs, the number of LBs was reduced. The number of mitochondria increased, and
      some of them became swollen and enlarged. However, by 72 hrs, the number of LBs
      increased and the ring-like arrangement of LBs around the nucleus again appeared.
      CONCLUSIONS: Ultrastructural changes of AT II cells following lung injury induced
      by LPS were time-dependent in young rats. Dex may ameliorate AT II cell injury
      and promote functional restoration of AT II cells in LPS-induced acute lung
      injury.

PMID- 18082030
TI  - [Plasma concentrations of vascular endothelial growth factor and tissue factor in
      children with acute lymphoblastic leukemia].
AB  - OBJECTIVE: To detect plasma concentrations of vascular endothelial cell growth
      factor (VEGF) and tissue factor (TF) in children with acute lymphoblastic
      leukemia (ALL) and explore their clinical significance in ALL. METHODS: Thirty
      three children with newly diagnosed ALL, including 18 cases of low risk, 7 cases
      of moderate risk and 8 cases of high risk, were enrolled in this study. Twenty
      five patients received a complete remission and 8 cases were in non-remission
      after conventional remission induction chemotherapy. Plasma concentrations of
      VEGF and TF in the patients were detected using ELISA before and after treatment.
      Sixteen healthy children served as normal control group. RESULTS: Plasma
      concentrations of VEGF and TF in ALL patients before treatment were significantly
      higher than those in normal controls (P < 0.01). Plasma concentrations of VEGF
      and TF in the non-remission group before treatment were significantly higher than
      those in the remission group (P < 0.05) and the control group (P < 0.01). After
      treatment the plasma concentrations of VEGF and TF in the non-remission group
      were not significantly reduced and higher than those in the remission and the
      control groups (P < 0.01). There were significant differences in plasma
      concentrations of VEGF and TF among the low-risk, moderate-risk and high-risk
      groups before and after treatment (P < 0.05). Plasma concentrations of VEGF and
      TF in the high risk group were not significantly reduced after treatment and
      higher than those in the control group (P < 0.01). A linear correlation was noted
      between plasma VEGF and TF concentrations in ALL patients before treatment
      (r=0.50, P < 0.01). CONCLUSIONS: VEGF and TF play an important role in the
      development of ALL and may be useful to the evaluation of the severity and the
      outcome in ALL.

PMID- 18082031
TI  - [Application of PCR-DGGE technique in G-6-PD deficiency].
AB  - OBJECTIVE: To detect gene mutations of children with glucose-6-phosphorate
      dehydrogenase (G-6-PD) deficiency and of carriers of G-6-PD deficiency gene with
      the technique of polymerase chain reaction and denatured gradient gel
      electrophoresis (PCR-DGGE), and to explore the value of the technique in the
      diagnosis of G-6-PD deficiency and G-6-PD deficiency gene carrying. METHODS:
      cDNAs were harvested by reverse transcription method after RNAs had been
      extracted from peripheral blood of 43 children with G-6-PD deficiency and of
      their family members (36 lineages). Electrophoresis behaviors of the fragment
      from exons 11-12 of G-6-PD cDNA were detected with the technique of PCR-DGGE.
      Gene sequencing was then performed for the abnormal electrophoresis bands.
      RESULTS: Abnormal electrophoresis bands were found in the 1304-1520 fragment of G
      6-PD cDNA in 33 out of 36 family lineages. The G-6-PD/6-PGD ratio was below 1.00
      in 9 mothers of patients. Three of them had the G-6-PD/6-PGD ratio lower than
      0.50. The PCR-DGGE bands were the same in the 3 mothers. Gene sequencing showed
      double heterozygote in the 3 mothers, but the maternal carriers of G-6-PD
      deficiency gene who had normal G-6-PD/6-PGD ratio showed mono-heterozygote in
      gene sequencing. Three mutational sites were found in the 1304-1520 fragment,
      i.e., C1311TG1376T and G1388A. The electrophoresis behaviors were different among
      the 3 gene mutational sites. CONCLUSIONS: PCR-DGGE is a sensitive and reliable
      technique in the screening of gene mutations. It is useful in the diagnosis of G
      6-PD deficiency, especially in the diagnosis of female G-6-PD deficiency gene
      carrying.

PMID- 18082032
TI  - [Interleukin-13 expression before and after pulse treatment with
      methylprednisolone in children with steroid-responsive nephrotic syndrome].
AB  - OBJECTIVE: To study serum concentration and mRNA expression of interleukin-13 (IL
      13) in children with steroid-responsive nephrotic syndrome (SRNS) and the effect
      of methylprednisolone pulse therapy (MPT) on IL-13 expression. METHODS: Twenty
      eight children with SRNS were enrolled in this study. Serum protein level of IL
      13 was measured using ELISA and IL-13 mRNA expression in peripheral blood
      mononuclear cells (PBMC) was detected with RT-PCR before MPT, 2 and 5 days after
      MPT, and 2 weeks after disappearance of proteinuria following MPT. Twenty-four
      urinary protein was measured with the biuret assay. Twenty healthy children were
      used as controls. RESULTS: Serum IL-13 levels (38.48 +/- 13.01 pg/mL vs 5.18 +/-
      2.71 pg/mL) and PBMC IL-13 mRNA expression (1.31 +/- 0.23 vs 0.36 +/- 0.07)
      before MPT in SRNS patients were significantly higher than in the controls. After
      5 days of MPT and 2 weeks after disappearance of proteinuria following MPT, serum
      IL-13 levels (15.33 +/- 7.81 and 5.35 +/- 2.12 pg/mL respectively) and PBMC IL-13
      mRNA expression (0.89 +/- 0.26 and 0.33 +/- 0.08 respectively) were significantly
      reduced (P < 0.01). Serum IL-13 levels and PBMC IL-13 mRNA expression in SRNS
      patients 2 weeks after disappearance of proteinuria following MPT were reduced to
      control levels, but remained at a higher level than controls 5 days after MPT. A
      positive correlation was found between serum levels of IL-13 and 24-hour urinary
      protein in SRNS patients before (r=0.75, P < 0.01) and after 2 and 5 days of MPT
      (r=0.68, r=0.71 respectively; P < 0.05). CONCLUSIONS: Serum IL-13 levels and PBMC
      IL-13 mRNA expression in children with SRNS increase. MPT can inhibit the
      expression of protein and mRNA of IL-13 in these patients.

PMID- 18082033
TI  - [Relationship between soluble intercellular adhesion molecule-1 and severe
      pneumonia].
AB  - OBJECTIVE: It has been reported that soluble intercellular adhesion molecule-1
      (sICAM-1) participates in many immune and inflammatory reactions. Its expression
      and role in severe pneumonia has not fully been understood. This study aimed to
      investigate the changes of sICAM-1 expression in severe pneumonia and the
      relationship between sICAM-1 and severe pneumonia in children. METHODS: Serum
      sICAM-1 levels were determined by the double antibody sand using ELISA in 50
      children with severe pneumonia and 56 children with mild pneumonia. Fifty-two
      healthy children served as control group. RESULTS: Serum sICAM-1 levels in
      children with severe pneumonia (402.36 +/- 31.24 mu g/L) were remarkably higher
      than those in the mild pneumonia group (278.86 +/- 36.24 mu g/L) at the acute
      stage and higher than in the control group (180.74 +/- 21.46 mu g/L) (P < 0.01).
      Serum sICAM-1 levels in children with severe pneumonia decreased significantly at
      the recovery stage (198.56 +/- 12.63 mu g/L) (P < 0.01), which were not
      statistically different from those in the mild pneumonia group at the recovery
      stage and the control group. There were no significant differences in serum sICAM
      1 levels among the severe pneumonia subgroups caused by different pathogens
      (bacteria, virus or Mycoplasma) at the acute stage. Serum sICAM-1 levels at the
      acute stage in children with severe pneumonia who were treated successfully were
      not significantly different from those in patients whose symptoms were partly
      improved. CONCLUSIONS: sICAM-1 might be involved in the inflammation course of
      severe pneumonia. It can severe as a marker of the diagnosis and the severity
      evaluation of severe pneumonia.

PMID- 18082034
TI  - [Comparison of clinical data of childhood asthma in different periods in
      Changsha].
AB  - OBJECTIVE: The incidence of childhood asthma is growing. This study aimed to find
      the changes of clinical features of childhood asthma over a 20-year period.
      METHODS: The medical data of 200 children with asthma between May 1986 and
      February 1988 (group 1) and of another 200 asthmatic children between June 2005
      and May 2006 (group 2) were studied retrospectively. RESULTS: Sixty-seven
      patients (33.5%) in group 1 and 128 patients (64.0%) in group 2 had concomitant
      allergic rhinitis (P < 0.01). The incidence of exercise-induced asthma, drug
      allergy and irritating smell allergy was significantly higher in group 2 than in
      group 1 (P < 0.05). Twenty-nine patients (14.5%) in group 1 and 112 patients
      (56.0%) in group 2 re-visited to the clinic (P < 0.01). The patients in group 1
      received nonspecific immune and desensitizing therapy but those in group 2
      received inhaled glucocorticoid therapy during the remission stage. After 3
      months treatment, asthma was in under control in 11 patients (37.9%, 11/29) in
      group 1 and in 93 patients in group 2 (83.0%, 93/112) (P < 0.01). CONCLUSIONS:
      The incidence of concomitant anaphylaxis increased in asthmatic children over a
      20-year period. The compliance of re-examination has increased in asthmatic
      children in recent years and this may be associated with a better efficacy of
      inhaled glucocorticosteroid therapy.

PMID- 18082035
TI  - [Sleep disorders and their influencing factors in primary school children from
      Urumqi].
AB  - OBJECTIVE: To understand the prevalence of sleep disorders and their influencing
      factors in primary school children from Urumqi. METHODS: A total of 2034 children
      at the ages of 6-14 years were randomly sampled in 3 districts of Urumqi. The
      children's sleep states and their family and social environments were
      investigated through questionnaires. RESULTS: The prevalence of sleep disorders
      in the subjects was 55%. The prevalence of sleep inquietude was the highest
      (14.7%), followed by sleep talking (4.8%), sleep walking (1.5%), nocturnal
      enuresis (1.5%), sleep teeth grinding (5.7%), habitual snoring (12.9%), sleep
      apnea (0.5%), and waking up by choke (1.9%). Taking drugs to stimulate or inhibit
      the central nervous system, frequent colds, confined housing area, family
      history, and sleeping with parents were risk factors for the development of sleep
      disorders. CONCLUSIONS: The prevalence of sleep disorders within primary school
      children in Urumqi is higher than the reported data. The development of sleep
      disorders is multifactorial.

PMID- 18082036
TI  - [Expression of CD21 in peripheral blood B lymphocytes of neonates].
AB  - OBJECTIVE: To study the cause of low immunologic function and insufficiency of
      immunoglobulin synthesis in neonates by detecting CD21 expression in B
      lymphocytes in different age group children. METHODS: This study consisted of
      three age group children: 2-26 days (n=18), 6 months-2 years (n=12) and 3-12
      years (n=17). CD21 expression in B lymphocytes was detected with flow cytometry.
      Serum levels of immunoglobulins were measured by immunoturbidimetry. RESULTS: The
      percentage and the number of B lymphocytes expressing CD21 in the neonate group
      were significantly lower than in the other two age groups. The neonate group also
      showed lower mean fluorescence intension (MFI) of CD21. The percentage and the
      number of B lymphocytes expressing CD21 as well as the MFI of CD21 increased
      significantly with the age. The serum levels of IgA and IgM in the neonate group
      were noticeably lower than those in the other two age groups. The serum levels of
      IgA and IgM also increased significantly with the age. CONCLUSIONS: Low CD21
      expression in B lymphocytes may be related to low function of humoral immunity in
      neonates.

PMID- 18082037
TI  - [Etiology and high risk factors of neonatal ventilator-associated pneumonia].
AB  - OBJECTIVE: Ventilator-associated pneumonia (VAP) is a common nosocomial infection
      and is responsible for a very high mortality in neonatal intensive care unit
      (NICU) patients. This study was designed to investigate the etiology and high
      risk factors of neonatal VAP. METHODS: The clinical data of 106 critical neonates
      who were treated with mechanical ventilator between 2003 and 2005 were studied
      retrospectively. RESULTS: Of the 106 neonates, 84 received mechanical ventilation
      for > or = 48 hrs. Thirty-five (41.7%) out of the 84 patients developed VAP.
      Univariate analysis showed that gestational age, duration of mechanical
      ventilation, reintubation, birth weights, primary lung disease and gamma globulin
      administration were associated with the development of VAP (P < 0.05).
      Multivariate stepwise logistic regression analysis showed that primary lung
      disease (OR=3.671, 95% CI=1.0-13.45, P < 0.05), duration of mechanical
      ventilation (OR=4.945, CI=1.51-16.21, P < 0.01), reintubation (OR=7.721, 95%
      CI=2.31-25.85, P < 0.01) and high-dose gamma globulin administration (OR=5.520,
      95%CI=2.08-16.26, P < 0.01) were predicted factors for the development of VAP.
      The detection rate of gram negative bacilli (76.9%) was the highest, followed by
      gram positive coccus (17.9%) in VAP patients. CONCLUSIONS: Opportunistic drug
      resistant bacteria are common pathogens for neonatal VAP. The risk of VAP is
      multifactorial, including external medical environments and patients' internal
      agents.

PMID- 18082038
TI  - [Measurement of B-lymphocyte stimulator mRNA expression in children with
      infectious mononucleosis by real-time fluorescence quantitative method].
AB  - OBJECTIVE: B cell multiplication plays a key role in infections mononucleosis.
      The present study was designed to detect the expression of B-lymphocyte
      stimulator (BLyS) mRNA in peripheral blood using real-time fluorescence
      quantitative polymerase chain reaction (RFQ-PCR) in children with infectious
      mononucleosis in order to explore the role of BLys in this disorder. METHODS:
      Specific primers and TaqMan probes of BLyS were designed, and fluorescence of the
      PCR products were detected continuously during amplification. According to the
      standard curves created by plasmid DNA, the expression level of target genes in
      clinical samples were calculated using Stata Software version 8.0, and the
      results were presented as the ratio of copies of target gene mRNA to beta2
      microglobulin (beta2M) mRNA copies. BLyS mRNA expression in peripheral blood was
      measured by RFQ-PCR in 18 children with infectious mononucleosis and the results
      were compared with those measured in 15 healthy controls. RESULTS: The range of
      target gene mRNA detected by REQ-PCR was from 109 ng/L to 101 ng/L. The
      coefficient of variation for intra-experimental and inter-experimental
      reproducibility ranged from 1.88% to 5.89% and 6.32% to 12.34%, respectively.
      BLyS mRNA expression in peripheral blood in children with infectious
      mononucleosis were significantly higher than that in controls (1.65+/-0.10 vs
      0.56+/-0.08; P < 0.01). CONCLUSIONS: RFQ-PCR has a high sensitivity and
      reproducibility for the measurement of BLyS mRNA expression. BLyS may be involved
      in the development of infectious mononucleosis.

PMID- 18082039
TI  - [Serum levels of IgG subclasses and vitamin A in children with recurrent
      respiratory tract infection].
AB  - OBJECTIVE: The development of recurrent respiratory tract infection (RRTI) is
      related to vitamin A deficiency and immune function abnormality in children. This
      study examined serum levels of IgG subclasses and vitamin A in children with
      recurrent respiratory tract infection. METHODS: Serum IgG subclasses levels
      (IgG1, IgG2, IgG3, IgG4) were detected using ELISA and serum vitamin A levels
      were detected using high performance liquid chromatography-Miller method in 80
      children with RRTI (ranged from 2-10 years old). The values were compared with
      those from 80 aged-matched healthy children. RESULTS: Serum levels of IgG2 (1.52
      +/- 0.18 g/L) and IgG4 (0.22 +/- 0.12 g/L) in children with RRTI were
      significantly lower than controls (IgG2: 2.23 +/- 0.08 g/L; IgG4: 0.28 +/- 0.01
      g/L) (P < 0.05). Serum vitamin A levels in children with RRTI were also
      significantly lower than controls (1.16 +/- 0.22 micromol/L vs 1.56 +/- 0.12
      micromol/L; P < 0.05). IgG2 and IgG4 deficiency (27%) was the most common in 22
      RRTI children with vitamin A deficiency. CONCLUSIONS: Serum levels of IgG
      subclasses, IgG2 and IgG4, and vitamin A decrease in children with RRTI. There
      might be some relationship between the decreased IgG2 and IgG4 levels and vitamin
      A deficiency.

PMID- 18082040
TI  - [Role and mechanism of Salvia miltiorrhiza Bunge in alleviating injury induced by
      hypoxia/reoxygenation in HK-2 cells].
AB  - OBJECTIVE: Salvia miltorrhiza Bunge (SMB) is a traditional Chinese herb, which is
      considered to promote blood flow and remove blood stasis. This study examined
      whether SMB can alleviate injury induced by hypoxia/reoxygenation (H/R) in human
      kidney proximal tubular cells-2 (HK-2 cells). METHODS: There were 3 experimental
      groups: control, H/R injury and SMB-treated H/R injury. H/R injury of HK-2 cells
      was induced by first covering the cells with and then removing liquid paraffin
      wax. Different concentrations of compound SMB solution (0.05%, 0.10%, 0.15% or
      0.20%) were administered to the SMB-treated H/R injury group before the hypoxic
      injury. After 4, 12 and 24 hrs of hypoxia and 4, 12, 24 and 48 hrs of
      reoxygenation, morphologic changes of HK-2 cells were observed under an inverted
      microscope. Cell viability was measured by the MTT method. Lactate dehydrogenase
      (LDH) activity in the culture supernatants was assayed using biochemical methods;
      TNF-alpha levels were determined by radioimmunoassay (RIA). RESULTS: The number
      of HK-2 cells was significantly reduced in the H/R injury group after hypoxia,
      and reached a nadir 24 hrs after hypoxia treatment. Various concentrations of SMB
      treated groups showed significantly greater number of HK-2 cells than the H/R
      injury group. SMB solution (0.10%) produced the best effect. The levels of LDH
      and TNF-alpha in the H/R injury group were significantly increased, and reached a
      peak between 24 hrs of hypoxia and 4 hrs of reoxygenation when compared to the
      control group. Pre-treating with 0.10% SMB resulted in significantly lower levels
      of LDH and TNF-alpha than in the untreated H/R injury group at various time
      points of H/R. CONCLUSIONS: SMB has protective effects against H/R injury of HK-2
      cells, possibly through inhibition of inflammatory cytokines.

PMID- 18082041
TI  - [Protective effects of heat shock preconditioning on the experimental autoimmune
      encephalomyelitis rats].
AB  - OBJECTIVE: To study the effects of heat shock preconditioning on the expression
      of heat shock protein-70 (HSP70) and apoptosis of the neuron in experimental
      autoimmune encephalomyelitis (EAE) rats. METHODS: Thirty-six Wistar rats were
      randomly divided into control, EAE and heat shock preconditioning groups (n=12
      each). The EAE animal model was induced with guinea pig myelin basic protein.
      Heat shock preconditioning was performed 24 hrs prior to the EAE model
      inducement. No treatment was done in the control group. The neurological signs
      were observed after immunization. The spinal cords were removed and stained with
      hematoxylin and eosin. HSP70 was detected by immunohistochemistry. Apoptosis of
      the neuron was measured by TUNEL. RESULTS: Heat shock preconditioning
      significantly alleviated clinical signs and neuronal injury. HSP70 expression in
      the heat shock preconditioning group was significantly higher than in the
      untreated EAE group (21.08 +/- 0.87 vs 10.17 +/- 0.51; P < 0.01). Heat shock
      preconditioning suppressed apoptosis of the neuron compared with the EAE group
      (apoptosis rate: 21.92 +/- 1.00% vs 58.92 +/- 1.67%; P < 0.01). CONCLUSIONS: Heat
      shock preconditioning might improve the neurological outcome in EAE rats,
      possibly through the induction of HSP70 synthesis and the reduction of apoptosis
      of the neuron in spinal cords.

PMID- 18082042
TI  - [Relationship between copper injury and apoptosis and the effect of curcumin on
      copper-injured BRL cells].
AB  - OBJECTIVE: To study the relationship between copper-induced apoptosis and
      reactive oxygen species (ROS) in BRL cells and the effect of curcumin, a plant
      derived polyphenol, on copper-injured BRL cells. METHODS: BRL cells were treated
      with CuSO4 (100 micromol/L) or curcumin + CuSO4. The BRL cells without any
      treatment were used as controls. Flow cytometry was applied to detect the
      production of ROS with fluorescent probe DCFH-DA. MTT colorimetry was used to
      evaluate cell activity. Apoptosis was measured using Hoechst 33258 staining and
      Annexin V-FITC and propidiumiodide (PI) staining. JNK/SAPK protein level was
      detected using Western blot. RESULTS: ROS levels (711.70 +/- 68.33 vs 87.22 +/-
      7.58) and apoptosis rate (45.08 +/- 1.87% vs 8.23 +/- 2.56%) of BRL cells reached
      to a peak after 6 hrs of CuSO4 treatment, which were significantly higher than
      controls (P < 0.01). JNK/SAPK levels increased significantly after 6 hrs of CuSO4
      treatment and peaked at 24 hrs of CuSO4 treatment compared with controls (P <
      0.01). Curcumin pretreatment decreased significantly ROS and JNK/SAPK levels as
      well as the apoptosis rate when compared with the CuSO4-treated alone group (P <
      0.01). CONCLUSIONS: Copper may induce apoptosis of BRL cells. ROS participated in
      apoptosis induced by copper. Curcumin produced protections on copper-injured BRL
      cells possibly by anti-oxidation and inhibition of p-JNK expression.

PMID- 18082043
TI  - [Effects of mouse bone marrow mesenchymal stem cells on the expression of
      chemokine receptors of spleenocytes after phytohemagglutinin stimulation].
AB  - OBJECTIVE: To explore the effect of mouse bone marrow mesenchymal stem cells
      (MSCs) on the expression of chemokine receptors in T lymphocytes in vitro.
      METHODS: Mouse bone marrow MSCs were separated with Percoll, cultured and
      expanded in low glucose DMEM. C57BL/6 mouse spleenocytes were cultured in the 24
      hole flasks by the density of 1 x10(6)/hole. Phytohemagglutinin (PHA) was then
      added to the holes and cultured for 72 hrs. This study consisted of three groups.
      Groups A and B were co-cultured by adding MSCs as the ratio of 0.1 and 0.01 to
      spleenocytes respectively. The control group was cultured without MSCs. Three
      days later the suspended spleenocytes were harvested for detecting the expression
      of three chemokine receptors CXCR3, CCR5 and CCR7 in T lymphocytes by the flow
      cytometry. RESULTS: The expression of CD3(+)CCR5(+) and CD3(+)CCR7(+) were
      statistically different among the three groups. Group A had the strongest
      expression, followed by group B and the control group. The expression of
      CD3(+)CXCR3(+) in group A was statistically higher than that in group B and the
      control group. CONCLUSIONS: MSCs could up-regulate the expression of chemokine
      receptors CXCR3, CCR5 and CCR7 in T lymphocytes stimulated by PHA.

PMID- 18082045
TI  - [5-azacytidine enhances anti-tumor efficacy of doxorubicin to neuroblastoma cell
      lines].
AB  - OBJECTIVE: The loss of caspase-8 expression correlates with unfavorable survival
      outcomes in neuroblastoma (NB). Caspase-8 gene inactivation is caused by
      methylation. This study aimed to explore the effect of the demethylation agent 5
      azacytidine on caspase-8 expression and whether 5-azacytidine can increase the
      sensitivity of chemotherapy drug doxorubicin to NB cells. METHODS: Caspase-8 mRNA
      expression in NB cell lines (SH-SY5Y cells) was examined by RT-PCR before and
      after 5-azacytidine treatment. Survival rates of SH-SY5Y cells were detected
      using MTT analysis and compared among the doxorubicin alone treatment, 5
      azacytidine along with doxorubicin treatment, and caspase-8 inhibitor+5
      azacytidine+doxorubicin treatment groups. RESULTS: Caspase-8 mRNA was not
      expressed in untreated SH-SY5Y cell lines. Caspase-8 mRNA expression in SH-SY5Y
      cells was detectable 3 days after 5-azacytidine treatment, and increased
      significantly 5 days after 5-azacytidine treatment (P < 0.05). Survival rates of
      SH-SY5Y cells treated with 5-azacytidine along with different concentrations of
      doxorubicin (0.05, 0.1,0.25, 0.5 microg/mL) were (77.61 +/- 7.30)%, (57.35 +/-
      6.64)%, (46.25 +/- 4.46)% and (35.59 +/- 5.12)%, respectively, which were
      significantly lower than those treated with doxorubicin alone (94.89 +/- 4.15%,
      80.60 +/- 8.50%, 64.48 +/- 4.92% and 52.32 +/- 6.71%) (P < 0.01). Caspase-8
      inhibitor pretreatment resulted in an increased survival rate of SH-SY5Y cells
      (92.95 +/- 3.48%, 78.39 +/- 4.28 %, 62.31 +/- 6.50% and 49.92 +/- 5.77%) compared
      with the 5-azacytidine+doxorubicin treatment group. CONCLUSIONS: 5-azacytidine
      may enhance anti-tumor efficacy of doxorubicin to NB cell lines, possibly through
      an up-regulation of caspase-8 mRNA expression.

PMID- 18082044
TI  - [Alterations of proadrenomedullin N-terminal 20-peptide in rats with pulmonary
      hypertension induced by high pulmonary blood flow].
AB  - OBJECTIVE: The mechanism of high pulmonary blood flow-induced pulmonary
      hypertension remains unclear. The aim of this study was to explore the effect of
      proadrenomedullin N-terminal 20-peptide (PAMP) on pulmonary hypertension, through
      examining the alterations of pulmonary PAMP expression and plasma PAMP
      concentration in rats with pulmonary hypertension induced by high pulmonary blood
      flow. METHODS: Sixteen male Sprague-Dawley rats were randomly divided into
      control (n=8) and shunt groups (n=8). Aortocaval shunting was produced in the
      shunt group. After 11 weeks of shunting, systolic pulmonary artery pressure
      (sPAP), diastolic pulmonary artery pressure (dPAP) and mean pulmonary artery
      pressure (mPAP) were evaluated by using a right cardiac catheterization
      procedure. The ultrastructural changes in intra-acinar pulmonary arteries were
      observed. The concentration of plasma PAMP was measured by radioimmunoassay. The
      expression of PAMP in pulmonary arteries was detected by immunohistochemical
      assay. RESULTS: sPAP, dPAP and mPAP were significantly increased in shunt rats
      compared with controls (P < 0.01). Ultrastructural changes, such as hyperplasia
      and swelling of endothelial cells, irregularity of internal elastic laminar, and
      hypertrophy and increased number of synthetic phenotype of smooth muscle cells,
      were found in intra-acinar pulmonary muscularized arteries in the shunt group.
      Plasma PAMP concentration (616 +/- 195 pg /mL vs 427 +/- 90 pg /mL) and PAMP
      expression in endothelial cells (0.62 +/- 0.09 vs 0.38 +/- 0.12) and in smooth
      muscle cells (0.24 +/- 0.07 vs 0.14 +/- 0.05) of pulmonary arteries increased
      significantly in the shut group compared with controls. CONCLUSIONS: The up
      regulation of pulmonary and plasm PAMP expression might be involved in the
      development of high pulmonary blood flow-induced pulmonary hypertension.

PMID- 18082046
TI  - [Influence of human cytomegalovirus infection on cell cycle and replication
      licensing factor Cdt1 in human embryonic lung fibroblastic cells].
AB  - OBJECTIVE: To study the influence of human cytomegalovirus (HCMV) infection on
      cell cycle and the expression of replication licensing factor Cdt1 in human
      embryonic lung fibroblastic (HEL) cells and to explore the pathogenesis of HCMV
      infection. METHODS: HEL cells were synchronized in the G0/G1 phase by the serum
      starvation method. The synchronized HEL cells were infected with HCMV, and those
      that were not subjected to HCMV infection were used as the control group. The HEL
      cells were harvested at 12, 24, 48, 72 and 96 hrs of HCMV infection. The cell
      cycle of HEL cells was detected by the flow cytometry. The expression of Cdt1
      mRNA in HEL cells was determined by reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: The cells in the G1 phase in the control group was
      significantly more than in the HCMV-infected group 12 and 24 hrs after infection
      (P < 0.01). The expression of Cdt1 mRNA in the HCMV-infected group was
      significantly lower 12 and 24 hrs after infection but increased significantly 48
      hrs after infection compared with the control group (P < 0.05). The expression of
      Cdt1 mRNA reached a peak at 12 hrs of infection in the control group, but at 48
      hrs of infection in the HCMV-infected group, which markedly lagged behind the
      control group. CONCLUSIONS: HCMV infection arrests the cell cycle of HEL cells at
      the G1 phase. HCMV infection makes Cdt1 expression delay. HCMV infection can
      interfere cell cycle of HEL cells possibly through affecting the expression of
      Cdt1.

PMID- 18082047
TI  - [Polymorphism of human cytomegalovirus UL134 gene in low-passage clinical
      isolates].
AB  - OBJECTIVE: Human cytomegalovirus (HCMV) displays genetic polymorphisms. Nineteen
      open reading frames (ORFs, UL133-UL151) found in the Toledo strain of HCMV and
      other low-passage clinical isolates may be essential for viral infection. This
      study aimed to analyze the polymorphism of HCMV UL134 gene in clinical isolates
      and explore the relationship between the polymorphism and HCMV infection.
      METHODS: PCR was performed to amplify entire UL134 region in 32 clinical
      isolates, which had been proven as HCMV-DNA positive by FQ-PCR. PCR products were
      sequenced. RESULTS: All of the 32 isolates were amplified and sequenced
      successfully. HCMV UL134 gene was highly conserved in the clinical isolates.
      UL134 ORF and its predicted protein in the clinical strains displayed 96.4%-98.3%
      nucleotide identity and 92.7%-94.9% amino acid identity respectively compared to
      those in the Toledo strain. A new posttranslational modification site,
      sulfationcamp (SUL) site, was found in UL134 protein of all of the clinical
      isolates except 35j. CONCLUSIONS: HCMV UL134 gene in clinical isolates was highly
      conserved. No substantial relation was found between UL134 gene and HCMV
      infectious diseases.

PMID- 18082048
TI  - [Rapamycin affects eIF- 4E expression in rat myocardial fibroblasts infected by
      Coxsackievirus B3].
AB  - OBJECTIVE: This study examined the effect of rapamycin, an inhibitor of mammalian
      target of rapamycin (mTOR), on eukaryotic initiation factor (eIF- 4E) expression
      in rat myocardial fibroblasts infected by Coxsackievirus B3 (CVB3) in order to
      identify the drug target for treatment of viral myocarditis. METHODS: Primary
      cultured rat myocardial fibroblasts were treated with CVB3 with multiplicity of
      infection (MOI=0.5 PFU/cell). The experiment consisted of four groups in which
      the cultured rat fibroblasts cells were treated with CVB3, rapamycin (10 nM) and
      CVB3 + rapamycin or placebo (control). Experimental model of CVB3-infected
      myocardial fibroblasts was confirmed by detection of CVB3 mRNA expression with RT
      PCR and observation of morphological changes of the infected cells with
      microscopy. eIF-4E expression was determined by both RT-PCR and Western Blot
      methods. RESULTS: Morphological changes were found in the fibroblasts treated
      with MOI 0.5 PFU/cell of CVB3 by transmission electron microscope and the viral
      particles were found in the cytoplasm. CVB3 mRNA was expressed in CVB3-infected
      fibroblasts after 1, 2, and 3 days after infection and 2 days after passage. The
      gray scale values of the eIF- 4E /beta -actin in the control, the CVB3, the
      rapamycin and the CVB3+rapamycin groups were 0.73 +/- 0.07, 0.87 +/- 0.03, 0.32
      +/- 0.03 and 0.56 +/- 0.04 respectively detected by RT-PCR, and were 0.79 +/-
      0.09, 1.35 +/- 0.12, 0.55 +/- 0.04, and 0.62 +/- 0.07 respectively detected by
      Western blot. EIF- 4E expression in the CVB3 group was higher than that in the
      control group. Both the rapamycin and the CVB3+rapamycin groups had lower eIF- 4E
      expression than the control and the CVB3 groups. CONCLUSIONS: CVB3 can infect
      myocardial fibroblasts and up-regulate the eIF- 4E expression in rat myocardial
      fibroblasts. Rapamycin can inhibit eIF- 4E expression and may be a potential
      medicine for treatment of viral myocarditis. It was suspected that mTOR/eIF- 4E
      signal pathway in rat myocardial fibroblasts might play an important role in the
      pathogenesis of viral myocarditis.

PMID- 18082049
TI  - [Effect of losartan on lung fibrosis in neonatal rats with hyperoxia-induced
      chronic lung disease].
AB  - OBJECTIVE: In addition to regulating blood pressure, angiotensin II is involved
      in lung fibrogenesis. This study aimed to explore the effect of losartan, an
      angiotensin II type 1 receptor antagonist, on lung fibrosis in neonatal rats with
      hyperoxia-induced chronic lung disease (CLD) and its possible mechanisms.
      METHODS: Neonatal Wistar rats were randomly divided into four groups within 24
      hrs after birth: room air exposure, hyperoxia exposure (85%-90% O2), hyperoxia
      exposure + losartan, and hyperoxia exposure + placebo. Losartan (5 mg/kg/d) or
      placebo was administered beginning on the 6th day after birth. After 7, 14 and 21
      days of exposure, 8 rats in each group were sacrificed. Lung histological changes
      were evaluated by hematoxylin-eosin staining. Levels of hydroxyproline (HYP),
      superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissues were
      determined by spectroscopy. RESULTS: Hyperoxia exposure resulted in decreased
      alveolar septation, enlarged terminal air space, increased collagen deposition,
      pulmonary hemorrhage, and pulmonary consolidation. In the hyperoxia exposure +
      losartan group, the alveolar septum became thinner and lung fibrosis was
      alleviated, but the alveolar space was not obviously deflated and the number of
      secondary septum was not increased. Hyperoxia exposure increased significantly
      the HYP contents in lung tissues 14 and 21 days after exposure. Addition of
      losartan to the hyperoxia exposure resulted in decreased HYP contents (471.46 +/-
      30.63 mu g/kg vs 545.15 +/- 34.90 mu g/kg for hypoxia alone; P < 0.01) after 21
      days of exposure. SOD activity increased 7 days after hyperoxia exposure and then
      decreased to levels similar to the air exposure group. MDA levels increased to a
      peak at 7 days and remained at higher levels through 21 days of exposure when
      compared with the air exposure group (P < 0.01). Losartan treatment significantly
      increased SOD activities (82.94 +/- 4.62 U/mg protein vs 67.78 +/-8.02 U/mg
      protein; P < 0.01) and decreased MDA levels (30.54 +/- 5.89 nmol/mg protein vs
      48.75 +/- 8.09 nmol/mg protein, P < 0.01) compared with the hyperoxia exposure
      group 21 days after exposure. CONCLUSIONS: Losartan attenuated lung fibrosis in
      neonatal rats with hyperoxia-induced CLD, possibly through an increase of
      antioxidase enzyme activity and reduction of lipid peroxidation.

PMID- 18082050
TI  - [Expression and roles of CDK4 and p21 in lung tissues of premature rats with
      hyperoxia-induced chronic lung disease].
AB  - OBJECTIVE: The pathogenic mechanisms of chronic lung disease (CLD) of premature
      infants are not fully understood. Its final pathological changes have been shown
      to relate with lung cell proliferation. The aim of the study was to explore the
      relationship of the expression of cyclin dependent kinase 4 (CDK4) mRNA and
      cyclin dependent kinase inhibitor (CDKI) p21 mRNA with lung cell proliferation.
      METHODS: Eighty premature rats were randomly assigned to a hyperoxia group and a
      control group (n=40 each). The hyperoxia group was exposed to high concentration
      of oxygen (FiO2 >0.90 and developed CLD. The control group was exposed to room
      air (FiO2 =0.21). The rats were randomly subdivided into groups sacrificed at 1,
      3, 7, 14 and 21 days of exposure. Lung tissues were collected and made into 5
      microm sections. Expression of proliferating cell nuclear antigen (PCNA) in lung
      tissues was detected by immunohistochemistry. Dynamic expression of CDK4 mRNA and
      p21 mRNA were detected by in situ hybridization. Lung histomorphology and
      fibrosis were observed by microscopy. RESULTS: Expression of PCNA and CDK4 mRNA
      of lung cells in the hyperoxia group increased significantly after 7 days of
      exposure, and further increased after 14 and 21 days compared with controls. p21
      mRNA expression in the hyperoxia group significantly increased after 1 and 3 days
      of exposure. After 7 days, p21 mRNA expression progressively decreased, but
      remained at a higher level than control through 21 days of exposure. PCNA
      expression was positively correlated to CDK4 mRNA expression (r=0.83, P < 0.05)
      and negatively correlated to p21 mRNA expression (r=-0.81, P < 0.05) in the
      hyperoxia group between 7 and 21 days of exposure. CONCLUSIONS: Hyperoxia can
      induce lung cell proliferation in premature rats. The over-expression of CDK4
      gene and the decreased expression of p21 gene in lung tissues may be associated
      with lung cell proliferation induced by hyperoxia.

PMID- 18082051
TI  - [Value of video-EEG in the diagnosis of childhood non-epileptic seizure].

PMID- 18082052
TI  - [Clinical analysis of 12 cases of Kawasaki disease complicated by Mycoplasma
      pneumoniae pneumonia].

PMID- 18082053
TI  - [Selective screening of inborn errors of metabolism in Foshan City: clinical
      analysis of 5 cases].

PMID- 18082054
TI  - [Relationship between psychological characteristics and the severity of asthma in
      children].

PMID- 18082055
TI  - [A case report of macrophage activation syndrome complicated by systemic onset
      juvenile idiopathic arthritis].

PMID- 18082056
TI  - [A case report of Alport syndrome with esophageal leiomyomatosis].

PMID- 18082057
TI  - [Unrelated umbilical cord blood transplantation for the treatment of childhood
      infantile malignant osteopetrosis: a case report].

PMID- 18082058
TI  - [Three children with Crohn's disease in one family].

PMID- 18082059
TI  - [Resistin-like molecules and inflammation response].

PMID- 18082060
TI  - [Roles of integrin-linked kinase in renal diseases].

PMID- 18082061
TI  - [Neonatal lupus syndromes].

PMID- 18082062
TI  - [Childhood lead poisoning (Part B)].

PMID- 18082063
TI  - Introducing early medical abortion in Australia: there is a need to update
      abortion laws.
AB  - Recent changes to Federal Therapeutic Goods Administration legislation have seen
      the limited introduction of the drug mifepristone to Australia for the purpose of
      early medical abortion. At the same time it has become evident that both
      methotrexate and misoprostol, licenced and available for other indications, are
      being used safely and appropriately for early abortion by Australian medical
      practitioners. Early medical abortion is widely practiced overseas where its
      safety and effectiveness are well supported by current evidence. However,
      abortion law in many states is still contained within the Criminal Codes and does
      not reflect current evidence-based abortion practice. In other states and
      territories restrictions on where abortions may be performed pose potential
      barriers to the introduction of mifepristone for medical abortion. There is an
      urgent need for abortion law to be clarified and made uniform across the country
      so that the best possible services can be provided to Australian women.

PMID- 18082064
TI  - Depression, social support and adherence to highly active antiretroviral therapy
      in people living with HIV/AIDS.
AB  - BACKGROUND: The present study investigated the prevalence of depression in HIV
      positive individuals and its association with adherence to highly active
      antiretroviral therapy (HAART). METHODS: HIV-positive (n = 80) and HIV-negative
      (n = 20) participants were assessed for depression and adherence via clinical
      interview and self-reporting. RESULTS: Fourteen percent of the HIV-seropositive
      group met the criteria for current mood disorder compared with 5% of controls.
      Similarly, 39% of the HIV-seropositive participants met the criteria for a past
      major depressive episode compared with 15% of controls. Non-adherence to HAART
      was reported by 30.5% of those prescribed HAART and was significantly associated
      with living alone and relationship status. CONCLUSIONS: The present study found
      compromised psychological health in people living with HIV infection. It is
      recommended that health professionals continue to screen for depression,
      relationship status and living situation to ensure adherence to HAART.

PMID- 18082065
TI  - Using epidemiological and molecular methods to investigate an outbreak of
      gonorrhoea associated with heterosexual contact in Newcastle, NSW, Australia.
AB  - BACKGROUND: We report a cluster of gonorrhoea among mainly heterosexual men that
      occurred in October 2005, which was first identified when routine weekly
      surveillance review procedures indicated a three-fold increase in reporting rates
      compared with historical data. METHODS: Each case was followed up with the
      treating medical officer to review treatment regimes and risk exposures, and to
      carry out enhanced contact tracing. The phenotype and genotype of the outbreak
      gonococcal isolates and gonococci prevalent in the months preceding and following
      the cluster were determined. Links between cases reported from the local Sexual
      Health Clinic and those reported by general practitioners were established.
      RESULTS: Laboratory data indicated that a particular gonococcal subtype (ST 225
      and NR/Brpyst) was prevalent during the outbreak. CONCLUSIONS: Gonorrhoea rates
      returned to pre-outbreak levels following a targeted health promotion
      intervention with no further cases of the outbreak subtype detected.

PMID- 18082066
TI  - Aboriginal women's stories of sexually transmissible infection transmission and
      condom use in remote central Australia.
AB  - BACKGROUND: Sexually transmissible infection (STI) rates are persistently high in
      central Australia, creating conditions for a potential HIV pandemic in the area.
      There is a shortage of qualitative research examining the underlying factors
      affecting STI transmission in this region. The present study investigates
      Aboriginal women's current levels of knowledge regarding STI and their
      transmission, perception of risk for STI, patterns of condom use, access to
      condoms and experiences of condom negotiation with their partners. It also
      explores the sociocultural context of their sexual health. METHODS: The present
      study used qualitative methods with a semistructured questionnaire. Twenty-four
      women aged 18-35 years from one remote central-Australian Aboriginal community
      were recruited. RESULTS: The results revealed poor understandings of STI
      transmission, limited access to condoms and low levels of condom use despite a
      high perception of risk to STI. They also identified specific issues facing these
      women regarding the sociocultural context of their condom use, their access to
      condoms and the transmission of STI. The perceived effects of alcohol abuse,
      infidelity, sexual assault and shame on the acquisition of STI were significant
      issues for the women. CONCLUSION: This research has identified an urgent need for
      further qualitative research into the sociocultural factors that facilitate the
      spread of STI among Aboriginal people of remote central Australia. Implications
      include the need to increase their knowledge regarding STI and STI transmission,
      to increase women's access to condoms and to incorporate the teaching of skills
      to deal with sexual assault and violence into sexual-health education.

PMID- 18082067
TI  - Adolescent girls' communication with partners about microbicide use.
AB  - BACKGROUND: Topical microbicides could be a female-controlled method of
      preventing sexually transmissible infections. Despite the possibility of
      surreptitious use, most women report that they would tell partners, and
      microbicides may be detectable. The purpose of the present study was to examine
      communication between adolescent girls and their partners regarding microbicides.
      METHODS: Girls (aged 14-21 years) participated in a 6-month study in which they
      were given vaginal moisturisers to use when they had intercourse. Data was
      collected about their demographics, sexual histories and conversations with
      mothers and partners. Both quantitative and qualitative analyses were conducted.
      RESULTS: Girls (n = 171) were asked about conversations with their partners.
      Talking with mothers and using the product were significantly related to talking
      with partners. Reasons for not talking were intrapersonal or interpersonal
      variables, the context of the relationship did not warrant an explanation and the
      lack of a decision to communicate. There seemed to be no difference in
      conversations for those who used or did not use. Girls had conversations with
      their partners when deciding to be in the study, when they were engaged in study
      activities or when deciding to use the product. Conversations about using the
      product focused on needing to use the product because of study demands, the
      lubricating properties or wanting to experience product use. CONCLUSIONS: Most of
      the girls talked to their partners and had positive conversations. Girls may need
      help initiating conversations and managing reluctant partners.

PMID- 18082068
TI  - General practice intervention to increase opportunistic screening for chlamydia.
AB  - We describe an 18-month intervention that was designed to improve opportunistic
      screening for chlamydia in General Practice. Key strategies included engaging and
      informing general practitioners, adopting a simplified screening protocol,
      providing feedback on practice testing performance and developing resources for
      use with patients. This uncontrolled before and after study found that the
      overall impact on testing was modest and largely transient, and was insufficient
      to impact on the current chlamydia epidemic. Major additional measures would be
      required to further substantially increase testing levels. These could include
      financial incentives linked to screening performance and increased community
      awareness to increase patient demand for testing.

PMID- 18082069
TI  - Evaluation, using two assessment instruments, of the American and British
      national guidelines for the management of sexually transmissible and genital
      infections.
AB  - BACKGROUND: The objective of the present study was to compare, utilising two
      guideline assessment instruments, six corresponding clinical practice guidelines
      of the British Association for Sexual Health and HIV and the Centres for Disease
      Control. METHODS: Three raters independently assessed the recently published
      guidelines for gonorrhoea, chlamydial infection, early syphilis, pelvic
      inflammatory disease, bacterial vaginosis and HIV testing using two instruments,
      the Cluzeau and the AGREE (Appraisal of Guidelines for Research and Evaluation
      instrument). The Cluzeau scores were a simple percentage comparison; the AGREE
      scores were a standardised score for each guideline development domain.
      Differences were assessed using the Wilcoxson signed ranks test. Inter-rater
      variability was calculated on the Cluzeau instrument utilising the intragroup
      correlation method. RESULTS: The British Association for Sexual Health and HIV
      guidelines scored higher than the Centres for Disease Control guidelines in many
      of the assessed domains. There were significant differences between the two in
      many of the scores (P = 0.026-0.028). Inter-rater concordance was high to very
      high at 0.70-0.83. CONCLUSIONS: There were often major differences in scores
      between the two guideline groups. It is necessary for wider discussion within the
      profession to consider the significance of these findings.

PMID- 18082070
TI  - Male sex work and HIV risk among young heroin users in Hanoi, Vietnam.
AB  - The present study describes complex drug and sexual risk in a group of male sex
      workers (n = 79) who were recruited in the context of a larger study of young
      heroin users in Hanoi, Vietnam (n = 1270). Male sex workers were significantly
      more likely than male non-sex workers to be migrants (P < 0.001) and to have
      unstable housing (P < 0.001), to have lifetime exposure to marijuana (P < 0.001),
      3,4 methylenedioxymethamphetamine (MDMA, ecstasy) (P < 0.01), amphetamines (P <
      0.05), cocaine (P < 0.01) and morphine (P < 0.001). Male sex workers are more
      likely to currently use MDMA (P < 0.05), amphetamines (P < 0.001), morphine (P <
      0.05) and to 'smoke' as their most frequent mode of heroin administration (P <
      0.01). Male sex workers are more likely to have both male and female concurrent
      sex partners (P < 0.001), to have a history of sexual victimisation (P < 0.001),
      to have had more than three different sex partners in the past 30 days (P <
      0.001), and to have had partners who injected drugs before sex (P < 0.001) or who
      used drugs during sex (P < 0.01). In their last sexual encounter with a client
      partner, approximately one-third (31.1%) reported having had receptive anal sex.
      In nearly three-quarters of these exchanges (71.4%), no condom was used.
      Similarly, in their last sexual encounter with a client partner, 42.2% reported
      having had insertive anal sex and in nearly half (47.4%) of these encounters no
      condom was used. Consistent with recent data from elsewhere in the region, there
      is an urgent need for additional research on male sex work in South-east Asia in
      order to properly situate behavioural interventions for male sex workers in this
      region.

PMID- 18082071
TI  - Sexual dysfunction in men treated with depot antipsychotic drugs: a pilot study.
AB  - BACKGROUND: Sexual dysfunction is common, but often under-recognised, in people
      with schizophrenia. Many antipsychotic drugs are known to cause prolactin
      elevation, and it is often assumed that sexual dysfunction is a consequence of
      prolactin elevation. We investigated the relationship between sexual function and
      serum concentrations of prolactin and testosterone in men receiving regular long
      acting depot injections of antipsychotic medication. METHODS: Twenty-two men
      attending a community depot clinic participated. A structured interview was used
      to collect information about sexual function, and serum prolactin and
      testosterone concentrations were measured. RESULTS: Sexual dysfunction was
      common, with 73% of men reporting problems in at least one area of sexual
      function. Six men had elevated serum prolactin and one had reduced serum
      testosterone. Antipsychotic drug dose was positively correlated with serum
      prolactin and negatively correlated with serum testosterone, but there was no
      association between serum prolactin or testosterone concentrations and any
      measure of sexual dysfunction. CONCLUSION: Sexual dysfunction is a major problem
      for men living with chronic schizophrenia, but our results suggest that it is not
      directly attributable to elevated prolactin or reduced testosterone
      concentrations.

PMID- 18082072
TI  - Young women's misperceptions about sexually transmissible infection testing: a
      'clean and clear' misunderstanding.
AB  - BACKGROUND: This exploratory study investigated young women's perceptions of
      sexually transmissible infection (STI) testing received during gynaecological
      care. Correlates of the incorrect perception that STI testing occurred were
      assessed. METHODS: Cross-sectional study of sexually active young women, age 18
      24 years, attending a university healthcare setting for gynaecological care (n =
      109). Two hundred and four women were approached and 87 were ineligible; of the
      remaining 117, 93.2% chose to enrol. RESULTS: Of the women enrolled, 25.7%
      falsely perceived that they were STI tested (labelled 'clean and clear'). Only
      approximately one in seven (14.7%) accurately understood the STI for which they
      were tested. In multivariate analyses, controlling for race, STI symptoms,
      depression, number of lifetime visits to the gynaecologist, and suspicion of
      current STI, three variables were significant: minority race (adjusted odds ratio
      (AOR) = 4.84, confidence interval (CI) = 1.38-16.96, P = 0.01), earlier age at
      sexual debut (AOR = 4.67, CI = 1.73-12.57, P = 0.002), and previous STI diagnosis
      (AOR = 3.38, CI = 1.07-10.66, P = 0.04). COMMENT: The findings suggest that many
      young women may have an inaccurate understanding of the STI testing they undergo
      during gynaecological care and may operate under the misperception they are
      'clean and clear' of STI. Women with said misperception were more likely to be of
      minority race and report relatively earlier age of sexual debut and previous STI
      diagnosis. Further investigation is warranted to determine whether the 'clean and
      clear' misperception influences young women's sexual risk behaviour.

PMID- 18082073
TI  - [Supraglottic and glottic carcinomas. Study of the incidence in the last 31
      years].
AB  - INTRODUCTION: Laryngeal carcinoma is a common neoplasia in our country. It is
      well-known that the supraglottis is more frequently involved in Mediterranean
      countries. We present our results on the incidence of neoplasias affecting
      supraglottis and glottis and we find a change in the normal trend. OBJECTIVE: To
      study the incidence of glottic and supraglottic tumours in our hospital over the
      last 31 years. We also analyze risk factors such as smoking and alcohol in the
      population of the Valencian Region. PATIENTS AND METHOD: We performed a
      retrospective review of 991 patients diagnosed as having carcinomas of the
      glottis and supraglottis between 1974 and 2005. The epidemiological data about
      the consumption of tobacco and alcohol in the population of the Valencian Region,
      Spain, are obtained from descriptive epidemiological studies (Health Statistics
      and the 2003 National Health Survey). CONCLUSIONS: With a total of 548 carcinomas
      of the glottis and 443 of the supraglottis, we find a change in the incidence
      maintained since 1990, with statistically significant differences (P=.0056).
      Thus, we can state that the glottis is more frequently affected than the
      supraglottis. Changes in the consumption of tobacco and alcohol cannot explain
      this current change.

PMID- 18082074
TI  - [Surgical complications in salvage surgery of patients with head and neck
      carcinomas treated with concomitant chemoradiotherapy (CCR)].
AB  - INTRODUCTION: One way of treating head and neck carcinomas is using concomitant
      chemoradiotherapy (CCR). In this study we will try to evaluate the incidence of
      complications in rescue surgery after CCR. MATERIAL AND METHOD: We have studied
      data from 103 patients diagnosed as having stage III or IV squamous head and neck
      carcinoma between 1997 and 2005. They were treated following two different CCR
      protocols. RESULTS: Of the 103 patients, 26 (25 %) required rescue surgery. Eight
      patients in this group (30.76 % of those operated on) presented complications.
      The average stay in our department was 52.8 days (7-197 days). CONCLUSIONS:
      Patients treated with CCR who have needed rescue surgery apparently have a higher
      rate of complications and a longer stay than those treated with surgery alone.

PMID- 18082075
TI  - [Auditory and corporal laterality, logoaudiometry, and monaural hearing aid
      gain].
AB  - INTRODUCTION AND OBJECTIVE: To identify the auditory or clinical test that has
      the best correlation with the ear in which we apply the monaural hearing aid in
      symmetric bilateral hearing loss. MATERIAL AND METHOD: A total of 37 adult
      patients with symmetric bilateral hearing loss were examined regarding the
      correlation between the best score in speech discrimination test, corporal
      laterality, auditory laterality with dichotic digits in Spanish and score for
      filtered words with monaural hearing aid. RESULTS: The best correlation was
      obtained between auditory laterality and gain with hearing aid (0.940).
      CONCLUSIONS: The dichotic test for auditory laterality is a good tool for
      identifying the best ear in which to apply a monaural hearing aid. The results of
      this paper suggest the necessity to apply this test in patients before a hearing
      aid is indicated.

PMID- 18082076
TI  - [Diagnosis of proximal gastro-oesophageal reflux in patients with rhonchopathy
      and sleep apnoea].
AB  - INTRODUCTION: The close relationship between gastro-oesophageal reflux disease
      and sleep-related breathing disorders allows the consideration of treatment with
      proton pump inhibitors as a feasible alternative for patients with snoring or
      mild to moderate sleep apnoea syndrome. Nevertheless, the presence of gastro
      oesophageal reflux in the proximal oesophagus must be identified objectively with
      a double channel oesophageal pH-metry. OBJECTIVE: To identify clinical data
      allowing the selection of patients most likely to have proximal oesophageal
      reflux, and, therefore, candidates for oesophageal pH-metry. MATERIAL AND METHOD:
      Between January 2004 and September 2006, 121 patients were prospectively
      included. In these patients, a nocturnal polysomnography and a 24 hour double
      channel pH-metry were performed on the same day. We compared statistically the
      clinical data, endoscopic examination of the upper airway and the pH-metry
      results. RESULTS: A good correlation was observed between the presence of
      symptoms suggesting pharyngo-laryngeal acid reflux and endoscopic examination of
      this area (P< .009). However, the comparison between clinical data and pH-metry
      results was not statistically significant. CONCLUSIONS: Clinical symptoms and
      endoscopic examination alone are not good tools to determine the presence of
      gastro-oesophageal reflux in the pharynx, in this group of patients. Its presence
      must be ascertained by a double channel oesophageal pH-metry.

PMID- 18082077
TI  - [Complications and sequelae in acoustic neuroma surgery].
AB  - OBJECTIVE: To evaluate the complications and sequelae of acoustic neuroma
      surgery, according to tumour size. PATIENTS AND METHOD: A retrospective analysis
      of 120 patients who underwent microsurgical resection of vestibular schwannomas
      between November 1994 and September 2006 was undertaken. Tumour size, extent of
      removal, preservation of facial and cochlear nerves, complications, and sequelae
      were considered. The degree of hearing preservation after surgery was determined
      by the Gardner-Robertson classification. RESULTS: There were 39 small (<1.5 cm),
      59 medium (1.5-3 cm), and 22 large tumours (>3 cm). Gross total resection was
      accomplished in 106 cases (88.3 %). The facial nerve was anatomically and
      functionally preserved in 103 cases on long-term follow-up (85.4 %). The cochlear
      nerve was functionally preserved (Gardner-Robertson class 1 and 2) in 54.4 % of
      the small tumours with useful preoperative hearing. Two patients died due to
      postoperative complications (mortality rate, 1.6 %), and 15 (12.5 %) developed a
      CSF leak. CONCLUSIONS: Despite the progress in the surgical treatment of acoustic
      neuromas, a considerable rate of complications and sequelae still remains.
      Therefore, there is a need to balance pros and cons of surgery in each patient
      according to the concurrent circumstances, as well as to consider other
      therapeutic strategies such as radiosurgery or a wait-and-see policy.

PMID- 18082078
TI  - [Organ preservation in laryngeal and hypopharyngeal cancer].
AB  - Organ preservation in advanced laryngeal and hypopharyngeal squamous cell
      carcinoma has been a major target for clinical research in the last years. For a
      long time, partial surgery and radiotherapy were the only options that could
      preserve the larynx. Partial surgery has developed new open techniques and, with
      the introduction of laser it continues to have a clear role in organ
      preservation. Radiotherapy seeks better results with the use of altered
      fractions. But, the real revolution began after 1980 with the introduction of
      chemotherapy that increased the options. Induction chemotherapy followed by
      radiotherapy where response is good has allowed the larynx to be preserved in
      about half of the cases, without jeopardizing survival. Concomitant
      chemoradiotherapy gives better results in preservation, and induction
      chemotherapy followed by concomitant chemoradiotherapy is under clinical
      research. Finally, new targeted treatments open up new fields in clinical
      research. With so many options and in view of the lack of a global agreement,
      more multidisciplinary clinical research is still needed in order to define the
      best strategy for each patient.

PMID- 18082079
TI  - [Unusual nasal clinical entities].
AB  - Three cases of rare entities in nasal pathology are reported. Two of them are
      high-grade lymphomas (T/NK type), with nasal blockage as the first symptom.
      Clinical course and treatment response are described. The third case refers to an
      infrequent benign nasal entity called angiocentric eosinophilic fibrosis. Its
      aetiology and management remains rather uncertain nowadays.

PMID- 18082080
TI  - [EXIT procedure in the management of severe foetal airway obstruction. the
      paediatric otolaryngologist's perspective].
AB  - The ex-utero intrapartum treatment (EXIT) procedure is a technique designed to
      allow partial foetal delivery via caesarean section with establishment of a safe
      foetal airway by either intubation, bronchoscopy, or tracheostomy while foetal
      oxygenation is maintained through utero-placental circulation. The most common
      indication for the EXIT procedure is the presence of foetal airway obstruction,
      which is usually caused by a prenatal diagnosed neck mass. We report three cases
      of head and neck tumours with airway obstruction treated by means of EXIT and
      with different solutions in the management of the airway. With the involvement of
      Paediatric Otolaryngologists in EXIT, new indications and select variations from
      the standard EXIT protocol should be considered.

PMID- 18082081
TI  - [The silent sinus syndrome].
AB  - The silent sinus syndrome is a very infrequent pathology. It is described as an
      enophthalmos secondary to collapse and opacification of maxillary sinus without
      presenting sinus or nasal symptoms. Osteomeatal complex obstruction is the
      triggering physiopathologic factor. The clinical symptoms and imaging findings
      lead to the diagnosis. The treatment consists in restoring sinus ventilation and,
      if necessary, correcting the orbital floor. We report a case of a woman who was
      diagnosed and treated because of this entity in our hospital.

PMID- 18082082
TI  - [Telangiectatic capillary haemangioma of the tympanic membrane].

PMID- 18082083
TI  - [Vestibular myogenic evoked potentials in patients with benign paroxysmal
      positional vertigo].

PMID- 18082084
TI  - [The new coagulation cascade and its possible influence on the delicate balance
      between thrombosis and hemorrhage].

PMID- 18082085
TI  - [Inflammation, atherosclerosis, classic cardiovascular risk factors,
      biostatistics, clinical significance. Where are we?].

PMID- 18082086
TI  - [Cardiovascular prevention: a compelling reason?].

PMID- 18082087
TI  - [Morbidity and mortality in patients treated with oral anticoagulants].
AB  - INTRODUCTION AND OBJECTIVES: The number of patients receiving oral anticoagulant
      therapy has increased markedly in recent years, with the consequence that
      monitoring must be decentralized. The aim of this study was to provide reference
      values for the quality of care in patients receiving oral anticoagulants at large
      specialized Spanish centers for use in future comparative analyses. METHODS: The
      records of 20,347 outpatients who were receiving oral anticoagulants between
      January and December 2003 at four large Spanish centers were assessed. Databases
      at the four hospitals were searched for severe adverse events. RESULTS: In total,
      211,987 regular check-ups were carried out, 72.7% of which gave international
      normalized ratios (INRs) within the range 2-4. Overall, 2369 hemorrhagic events
      were observed, 190 (8%) of which were severe, with 20 deaths (0.1 per 100 patient
      years). In addition, there were 299 thromboembolic events, with 11 deaths (0.05
      per 100 patient-years). The frequency of these events was greater in patients
      with a cardiac prosthesis, who required more intense anticoagulation. The
      incidence of death with different diagnoses was also greater in anticoagulated
      patients with a cardiac prosthesis, and the highest probability of death (1 in 3)
      was associated with episodes of cerebral hemorrhage. The incidence of hemorrhage
      increased as the INR increased. In contrast, thrombotic events occurred
      principally when the INR was below 2, and were not observed with INRs over 6.
      CONCLUSIONS: The incidence of adverse events in patients receiving oral
      anticoagulant therapy at large Spanish centers was similar to that observed in
      other European countries.

PMID- 18082088
TI  - [Prognostic value of tumor necrosis factor-alpha in patients with ST-segment
      elevation acute myocardial infarction].
AB  - INTRODUCTION AND OBJECTIVES: Tumor necrosis factor-alpha (TNFalpha in patients
      with ST-segment elevation myocardial infarction (STEMI). The aim of this study
      was to determine the prognostic value of TNFalpha in this clinical setting at six
      month follow-up. METHODS: The levels of TNFalpha, C-reactive protein (CRP),
      interleukin 6 and type 1 soluble intercellular adhesion molecules measured within
      the first 10 h of symptom onset and at 48 h in 74 consecutive patients admitted
      with STEMI. The relationships between these levels and the incidence of ischemic
      events (i.e., angina, reinfarction, and death), heart failure (HF), or both
      (i.e., all cardiovascular events) were studied. RESULTS: Overall, TNFalpha levels
      were significantly higher in patients who had an ischemic event or HF than in
      those who did not (P<.02 for both). At 48 h, the adjusted odds ratios of those in
      the highest TNFalpha quartile (2.92 pg/mL) for the development of ischemic
      events, HF, and all cardiovascular events combined were 13.1, 9.59 and 9.75,
      respectively. A TNFalpha level of 2.04 pg/mL at 48 h had a sensitivity of 78% and
      a specificity of 72.5% in predicting a cardiovascular event of any form. The CRP
      level, but not the TNFalpha level, at admission was found to be an independent
      predictor of the development of a cardiovascular events. CONCLUSIONS: In patients
      with STEMI, the plasma TNFalpha level 48 h after symptom onset and the CRP level
      at admission were independent predictors of cardiovascular events.

PMID- 18082089
TI  - [Rosuvastatin and metformin decrease inflammation and oxidative stress in
      patients with hypertension and dyslipidemia].
AB  - INTRODUCTION AND OBJECTIVES: Both hypertension and dyslipidemia raise the risk of
      cardiovascular disease because they have proinflammatory effects and increase
      oxidative stress. The aim of this study was to evaluate the effects of
      rosuvastatin and metformin on inflammation and oxidative stress in patients with
      hypertension and dyslipidemia. METHODS: This open parallel-group clinical study
      involved 48 patients with hypertension and dyslipidemia. Of these, 16 were
      treated with rosuvastatin, 10 mg/day, while 16 received metformin, 1700 mg/day,
      and the 14 in the control group received starch placebo, 10 mg/day. The following
      variables were recorded during the study: age, weight, body mass index, blood
      pressure, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol,
      high-density lipoprotein (HDL) cholesterol, triglycerides, interleukin-6 (IL-6),
      tumor necrosis factor-alpha (TNFalpha) glutathione reductase (GSH), glutathione
      peroxidase (GPx), and superoxide dismutase (SOD). RESULTS: Administration of 10
      mg/day of rosuvastatin decreased total cholesterol by 41.7%, LDL cholesterol by
      63.0%, and triglycerides by 10.7%, and increased HDL cholesterol by 6.3%.
      Pharmacological treatment with either rosuvastatin or metformin lead to
      reductions in IL-6, TNFalpha, GSH and GPx levels and an increase in the SOD
      level, and there were significant interactions between the two treatment groups
      for these variables. CONCLUSIONS: Rosuvastatin improved the lipid profile.
      Moreover, both rosuvastatin and metformin reduced inflammation and oxidative
      stress. These results demonstrate the presence of an additional cardioprotective
      effect, which may result from a direct mechanism of action or be a pleiotropic
      effect. Further long-term studies are required to determine whether rosuvastatin
      or metformin can be used to decrease the cardiovascular risk resulting from
      oxidative stress and inflammation.

PMID- 18082090
TI  - [Coronary disease risk attributable to cardiovascular risk factors in the Spanish
      population].
AB  - INTRODUCTION AND OBJECTIVES: The proportion of the ischemic heart disease (IHD)
      burden attributable to cardiovascular risk factors in Spain has traditionally
      been extrapolated from populations in other countries. The aim of this study was
      to estimate the IHD risk attributable to smoking, hypercholesterolemia,
      hypertension, diabetes and excess weight using data from studies carried out in
      the Spanish population. METHODS: Data on the prevalence of cardiovascular risk
      factors in the general population were obtained from a meta-analysis of 48 cross
      sectional studies carried out in Spain, and data on corresponding prevalences
      among IHD patients were derived from the PRIAMHO II and PREVESE II multicenter
      hospital registries. Crude and adjusted relative risks of IHD were obtained from
      follow-up data collected over 5 years in a primary-care cohort of 6124 adults
      without cardiovascular disease. The crude and adjusted population attributable
      fractions for various risk factors were calculated for both sexes combined and
      for men and women separately. RESULTS: Among men, 42.5% (95% confidence interval
      [CI] 6.8%-59.6%) of the adjusted incidence of IHD was attributable to overweight,
      33.9% (95% CI 22.6%-41.0%) to smoking, 19.4% (95% CI 8.2%-26.5%) to
      hypercholesterolemia, and 15.5% (95% CI 1.6%-24.6%) to hypertension. Among women,
      36.5% (95% CI -8.0%-56.3%) of IHD cases were attributable to overweight, 24.8%
      (95% CI 12.0%-31.9%) to diabetes, and 20.1% (95% CI 6.1%-28.6%) to
      hypercholesterolemia. CONCLUSIONS: The cardiovascular risk factors found to
      contribute most to IHD in the Spanish population were excess weight in both
      sexes, followed by smoking in men.

PMID- 18082091
TI  - [Blood pressure control in hypertensive patients with left ventricular
      hypertrophy. The VIIDA Study].
AB  - INTRODUCTION AND OBJECTIVES: The aims were to determine the effectiveness of
      blood pressure (BP) control in hypertensive patients with left ventricular
      hypertrophy (LVH), as detected by ECG, and to identify the variables associated
      with poor control, particularly in diabetics. METHODS: The study included
      hypertensive patients with ECG evidence of LVH who attended cardiology outpatient
      clinics between April 2003 and November 2004. Patient characteristics and
      clinical variables were recorded on admission to the study. RESULTS: Of the
      16,123 patients included, 4037 (25.04%) had LVH at presentation. Some 58.1% of
      these latter patients had a history of cardiovascular disease. Only 8.1% of
      diabetic patients had BP values below 130/80 mmHg, whereas 22.4% of nondiabetic
      patients were well-controlled. Multivariate analysis showed that the only
      independent predictors of poor BP control were diabetes (odds ratio [OR] 3.62,
      95% confidence interval [CI] 2.7-4.7), female sex (OR 1.18, 95% CI 1.02-1.33),
      increased voltage recording in lead V5 (OR 1.027 per mm, 95% CI 1.01-1.03), and
      body mass index (OR 1.03, 95% CI 1.00-1.05), whereas a history of cardiovascular
      disease was associated with good BP control (OR 0.57, 95% CI 0.48-0.70).
      CONCLUSIONS: The prevalence of LVH, as identified by ECG, was high in
      hypertensive patients attending cardiology outpatient clinics, and comorbid
      conditions were common. Control of BP was suboptimal, particularly in diabetic
      patients, fewer than 10% of whom were well-controlled. Finally, BP control in
      patients with LVH was influenced by sex, body mass index, and a history of
      cardiovascular disease.

PMID- 18082092
TI  - [Influence of cardiopathy etiology on responses to cardiac resynchronization
      therapy].
AB  - INTRODUCTION AND OBJECTIVES: Little is known about how responses to cardiac
      resynchronization therapy (CRT) are affected by the nature of the underlying
      cardiopathy. The aim of this study was to investigate how cardiopathy etiology
      influences the effect of CRT on reverse left ventricular remodeling. METHODS: The
      study included 106 patients with left ventricular systolic dysfunction and left
      bundle branch block (LBBB) who were receiving CRT. Clinical and echocardiographic
      investigations were performed at baseline before implantation and at 6 and 12
      month follow-up to determine left ventricular diameter, volume and systolic
      function, and to quantify mitral regurgitation. RESULTS: During follow-up, it was
      observed that CRT reduced left ventricular volume and diameter, increased left
      ventricular ejection fraction (LVEF), and reduced mitral regurgitation severity
      irrespective of the etiology of the cardiopathy. In patients with ischemic
      dilated cardiomyopathy, LVEF increased by 34% and end-diastolic and end-systolic
      volumes decreased by 4% and 12%, respectively; in those with idiopathic dilated
      cardiomyopathy, LVEF increased by 38% and end-diastolic and end-systolic volumes
      decreased by 13% and 19%, respectively (P=NS for ischemic vs. non-ischemic
      disease). Nor were differences observed between the groups in clinical outcome:
      74% of the ischemic group responded compared with 62% of the non-ischemic group
      (P=NS). CONCLUSIONS: At 12-month follow-up, patients with left ventricular
      systolic dysfunction and LBBB treated by CRT showed clinical improvements and
      demonstrated reverse ventricular remodeling, irrespective of the etiology of
      their cardiopathy.

PMID- 18082093
TI  - [European practice guidelines on cardiac pacemakers and cardiac resynchronization
      therapy. Working Group of the European Society of Cardiology (ESC) on cardiac
      pacemakers and cardiac resynchronization therapy. Developed in collaboration with
      the European Heart Rhythm Association].

PMID- 18082094
TI  - [Spanish Cardiac Catheterization and Coronary Intervention Registry. 16th
      Official Report of the Spanish Society of Cardiology Working Group on Cardiac
      Catheterization and Interventional Cardiology (1990-2006)].
AB  - This article summarizes the data reported to the 2006 registry of the Spanish
      Society of Cardiology Working Group on Cardiac Catheterization and Interventional
      Cardiology. Data were obtained from 135 centers. Of these, 125 performed
      catheterizations mainly in adults, while 10 carried out procedures in pediatric
      patients only. In 2006, 126,196 diagnostic catheterizations were carried out. Of
      these, 113,228 were coronary angiograms, 7.6% more than in 2005. The population
      adjusted rate was 2560 coronary angiograms per million inhabitants. A total of
      57,041 percutaneous coronary interventions were performed, which was 7.8% more
      than in the previous year and which corresponds to a rate of 1293 per million
      inhabitants. Stents were used in 96.1% of coronary interventions. Overall, 90,006
      stents were implanted, of which 59.3% were drug-eluting stents. Moreover, 10,067
      interventions were carried out for acute myocardial infarction, 20.6% more than
      in 2005 and accounting for 17.6% of all percutaneous coronary interventions. Non
      coronary interventions were most frequently performed for adult congenital heart
      disease, with closure of an atrial septal defect being the most numerous, at 334
      procedures. Percutaneous mitral valvuloplasties were performed in 431 cases, a
      similar figure to that recorded in the previous registry, and the success rate
      was 93.6%. Each year, radial access continues to be used more frequently for
      coronary procedures. Finally, it is important to emphasize that a high percentage
      of laboratories reported results, which ensures that the data presented here can
      serve as an international reference source for percutaneous cardiac interventions
      performed in Spain.

PMID- 18082095
TI  - [Spanish Implantable Cardioverter-Defibrillator Registry. Third Official Report
      of the Spanish Society of Cardiology Working Group on Implantable Cardioverter
      Defibrillators (2006)].
AB  - INTRODUCTION AND OBJECTIVES: To report the 2006 findings of the Spanish
      Implantable Cardioverter-Defibrillator (ICD) Registry, established by the Working
      Group on Implantable Cardioverter-Defibrillators, Electrophysiology and
      Arrhythmia Section, Spanish Society of Cardiology. METHODS: Each ICD team
      voluntarily reported data to the Spanish Society of Cardiology by completing a
      single-page questionnaire. Prospective data were collected on 91.8% of
      implantations. RESULTS: In total, 2679 implantations were reported to the
      registry (86.6% of the estimated total). The reported implantation rate was 60
      per million inhabitants, and the estimated rate was 69 per million. The
      proportion of first implantations was 80%. The majority of ICDs were implanted in
      males (mean age 61.5 [14] years) with severe or moderate-to-severe left
      ventricular dysfunction who were in functional class II or I. Ischemic heart
      disease was the most frequent etiology, followed by dilated cardiomyopathy. This
      is the first year that half of first device implantations were carried out for
      primary prevention, with substantial increases among patients with ischemic heart
      disease and dilated cardiomyopathy. The number of ICDs incorporating cardiac
      resynchronization therapy has continued to grow, and now comprises 28.6% of all
      devices implanted. As in the previous year, around 70% of ICD implantations were
      performed in an electrophysiology laboratory by a cardiac electrophysiologist.
      The incidence of complications during device implantation was very low.
      CONCLUSIONS: The 2006 Spanish Implantable Cardioverter-Defibrillator Registry
      contains data on more than 86% of all ICD implantations performed in Spain. Half
      of first device implantations were carried out for the purposes of primary
      prevention.

PMID- 18082096
TI  - [Spanish Pacemaker Registry. Fourth Official Report of the Spanish Society of
      Cardiology Working Group on Cardiac Stimulation (2006)].
AB  - INTRODUCTION AND OBJECTIVES: The aim of this report was to describe the results
      of an analysis of the data on pacemaker implantations reported to the Spanish
      Pacemaker Registry during 2006. Special emphasis was placed on sociodemographic
      characteristics and on the pacing modes implemented for different
      electrocardiographic indications. METHODS: The data collected comprised all the
      information recorded with the European Pacemaker Patient Identification Card.
      Special software was used for the analysis. RESULTS: Information was received
      from 105 centers and involved a total of 10,401 cards. It represented 35% of all
      pacemakers implanted during 2006. The majority of implantations (57.5%) were
      performed in males, and this applied to all age decades, except the 90s. The
      average age of patients who received a first implant was 75 years.
      Atrioventricular block accounted for the greatest number of electrocardiographic
      indications. Some 25% of patients with sinus node disease received VVI/R pacing
      despite remaining in sinus rhythm. In addition, 1.5% of implanted devices
      provided cardiac pacing for ventricular resynchronization, and did not have an
      associated defibrillator function. Almost all the leads used were bipolar, with
      only 0.6% being unipolar. In addition, 35.2% of leads were active-fixation leads,
      while 24.3% of generator used throughout the year were for pulse generator
      replacement. Some 2.4% of generator replacements were due to erosion or
      infection. CONCLUSIONS: The number of pacemaker implantations and the incidence
      of conduction disturbance were both greater in males. Correspondingly, first
      implantations were carried out at a slightly younger age in males. The age decade
      during which the greatest number of pacemaker implantations was carried out was
      the 70s, followed by the 80s. Age was one of the factors that influenced the
      suitability of the pacing mode. In a significant percentage of patients, the
      pacing mode was inappropriate. The use of active-fixation electrodes continues to
      increase.

PMID- 18082097
TI  - [Congenital subaortic diverticulum].

PMID- 18082098
TI  - [Prognostic significance of creatinine clearance rate in patients with heart
      failure and normal serum creatinine].
AB  - Kidney failure is an important prognostic factor in patients with heart failure.
      Renal function is usually evaluated by measuring the serum creatinine level.
      However, a normal creatinine level can mask established kidney failure. We
      investigated the prognostic significance of the estimated creatinine clearance
      rate (Cockcroft formula) in 235 patients with heart failure and a normal serum
      creatinine level. The two-year mortality rate was significantly higher in
      patients who had established kidney disease (i.e., a creatinine clearance rate
      <60 mL/min) than in those who did not (35.1% vs. 10.1%, P<.001). Even when only
      patients without established kidney failure were analyzed, the creatinine
      clearance rate had prognostic significance (rate > or = 90 mL/min, mortality
      3.2%; rate 89-60 mL/min, mortality 13.9%; P=.02). On Cox regression analysis,
      which included age, sex, heart failure etiology, left ventricular ejection
      fraction, diabetes and hypertension, the creatinine clearance rate remained an
      independent predictor of mortality.

PMID- 18082099
TI  - [Nuclear changes and p62 expression in ischemic and dilated cardiomyopathy].
AB  - The study's objectives were to investigate nuclear stereology and to determine
      the level of p62, a protein involved in nuclear transport, in human
      cardiomyocytes from patients with heart failure due to ischemic cardiomyopathy
      (ICM) or dilated cardiomyopathy (DCM). We studied 23 human hearts: 10 had ICM, 10
      had DCM, and three were from control subjects. The size of the nucleus was
      significantly increased in ICM and DCM hearts compared with those from controls
      (by 60% and 66%, respectively, P=.03), as was the size of the nucleolus (by 59%,
      P=.02 and 75%, P=.03, respectively). In addition, the p62 level was significantly
      increased in both forms of cardiomyopathy compared with controls (ICM 110%,
      P=.01; and DCM 145%, P=.04). In the ICM group, there were correlations between
      the p62 level and nuclear size (r=0.615, P=.05) and between the p62 level and the
      heterochromatin percentage (r=-0.707; P=.02). In conclusion, cardiomyocytes from
      hearts affected by ICM and DCM showed changes in nuclear and nucleolar
      morphology. The p62 level had doubled in both forms of cardiomyopathy and, in ICM
      hearts, there was a correlation with nuclear changes.

PMID- 18082100
TI  - [Revista Espanola de Cardiologia 2007: scientific impact, manuscript management,
      activity, and diffusion].

PMID- 18082101
TI  - [Endovascular treatment of acute type-B aortic dissection through the ascending
      aorta].

PMID- 18082102
TI  - [Long-chain 3-hydroxyacyl-coenzyme a dehydrogenase deficiency and
      cardiomyopathy].

PMID- 18082103
TI  - [Expert consensus document on Beta-adrenergic receptor blockers and cocaine use].

PMID- 18082105
TI  - [The "Gretchen question" for psychiatry--the importance of religion and
      spirituality in psychiatric treatment].
AB  - OBJECTIVE: The subject of religion and spirituality has attracted little
      attention in psychiatric research so far. The aim of the study was to give an
      overview of the attitudes of patients as well as psychiatrists towards regarding
      the importance of religion and spirituality in the treatment of mental illness.
      Furthermore we tried to give a description of established ideas involving both
      dimensions into the treatment of psychiatric patients. METHODS: We performed a
      search for relevant literature using the electronic databases Medline, PubMed,
      Psyndex and Embase. In addition we used the internet search engines Scopus and
      Google Scholar. RESULTS: Patients mention religion twice as often as an important
      factor in their lives as compared to psychiatrists. Consecutively, particular
      emphasis should be paid to the integration of both dimensions into clinical
      treatment. Additionally, the education of mental health professionals,
      consultation and the enrollment of religious or spiritual needs of patients when
      taking their medical history are essential factors. Religious coping and positive
      and negative components in matters of mental health are highlighted. CONCLUSIONS:
      More attention should be paid to the "religiosity gap" between patients and their
      psychiatrists. The entirety of a human being includes a physical, emotional,
      social as well as a spiritual dimension. Mental health professionals ignoring one
      of these aspects may delay recovery.

PMID- 18082106
TI  - [Are there substantial reasons for contraindicating antidepressants in bipolar
      disorder? Part III. The alternatives!].
AB  - After having described depressive symptoms along the course and different
      subtypes of bipolar disorder the authors focus on pharmacological alternatives to
      antidepressant medication in bipolar depression. In doing so, they review the
      newest literature on efficacy of antidepressants and compare effect size of the
      different alternatives like antipsychotics and mood stabilizers to those of
      antidepressants. Efficacy of antidepressants in bipolar depression is still
      discussed controversially, as scientific evidence, is as far as available, weak.
      Severity of depressive symptoms should define, wether or not antidepressants in
      comparison to alternative agents like antipsychotics or mood stabilizers should
      be implemented. According to a balanced analysis of pro's and con's
      antidepressants may be used in minor to medium depressive symptoms as well. For
      clinical safety reasons, and not due to scientific evidence, an antimanic agent
      should be implemented in addition to an antidepressant. Because of clinical
      wisdom, in patients with mixed episodes or rapid cycling antidepressants should
      be avoided.

PMID- 18082107
TI  - [The cardiovascular risk of schizophrenic patients].
AB  - OBJECTIVE: Schizophrenia is associated with increased cardiovascular mortality.
      The deceleration capacity of heart rate is discussed to be a predictor of
      mortality, more powerful than conventional measures of heart rate variability
      (HRV) or the left ventricular ejection fraction. The aim of this study was to
      determine whether patients with schizophrenia, receiving antipsychotic medication
      have a reduced HRV indicating an elevated mortality risk. METHODS: We quantified
      HRV and the deceleration capacity in 24-hour electrocardiogram recordings from 28
      medicated patients with schizophrenia and 28 matched controls. In addition to the
      evaluation of the 24-hour recording, 4-hour periods of "sleep" and "wake"
      recordings were evaluated separately, as activity has a major influence on HRV.
      Actigraphy was used to identify coherent sleep and wake phases and to ensure
      comparable levels of activity in patients and controls. RESULTS: Medicated
      patients showed a significant reduction of the HRV. The HRV was reduced
      significantly according to the time domain and frequency domain measures. The
      deceleration capacity of medicated patients was 5.36 compared with 8.26 for the
      controls (p < .05). CONCLUSIONS: Heart rate deceleration capacity is
      significantly reduced in schizophrenic patients treated with antipsychotics and
      may serve as an indicator of increased cardiovascular mortality risk.

PMID- 18082108
TI  - [Minor relatives of schizophrenia patients: burden and needs].
AB  - OBJECTIVES: The aim of the present study was to investigate the burden of minor
      relatives of schizophrenia patients and of the needs for support for the
      relatives. METHODS: 135 relatives of patients with schizophrenia or
      schizoaffective disorders were assessed by using the "Involvement Evaluation
      Questionnaire" and the "Carers' Needs Assessment for Schizophrenia". RESULTS:
      24.4% of the total sample (N=33) had minor (i.e. below 18 years) siblings (N=18)
      or children (N=15). If the patient had minor siblings, almost the half of the
      adult relatives reported moderate or severe problems. However, among those
      patients who had to take care for minor children, only a fifth reported moderate
      or severe problems. Among the patients' offsprings being under the age of 16
      behavioural disturbances, reduced appetite and other consequences of the disease
      were reported frequently. CONCLUSIONS: These results indicate that patients with
      schizophrenia or schizoaffective disorders often have minor relatives in their
      family frequently suffering from marked burden.

PMID- 18082109
TI  - [Psychosis sight from the complexity research--a model for the examination of the
      self organisation of a dysfunctional self].
AB  - Nowadays the multifactorial genesis of psychotic illnesses is undisputed. The
      question of the integration of the multilayered results is open from the
      biological, emotional and social area. Based on the results of the complexity
      research (chaos theory, theory of the self organisation) the hypothesis was
      formulated for the emergence of psychotic illnesses that these are understood
      themselves as an expression of a dysfunctional self. Such a dysfunctional self
      arises in a self organizing process. MATERIAL AND METHOD: The definition of the
      self was newly formulated. This happened on the knowledge of the complexity
      research and a bio- psycho-social model of illness and health. Ten main
      categories were defined, which seem essential for the development of a healthy,
      this means a flexible and autonomous self. In further consequence, based on these
      categories, a semistructured interview guide was developed. With this interview
      guide the information about the quality of the self organising process of the
      development of the self was collected. This guide was tested in the context of a
      master thesis in a multidimensional interview with a schizophrenic patient and
      his family. This interview was taken on video tap. The information on video
      became transcribed. Than the information was examined qualitatively to two
      aspects. This happened with the help of a qualitative contents analysis. The
      first aspect concerned the decision of the assignment to one or several of the
      ten categories. In a 2nd step it was judged, whether the examined information has
      to be classified as beneficial for the development of a healthy self or as
      impeding. RESULTS: The developed and used examination model is suitable to make
      the investigation of a self organizing self possible. At the individual case
      analysis of a patient with a schizophrenic psychosis the inhibiting influences
      for the development of a healthy self predominated at a large part of the 10
      categories. This corresponded to the hypothesis. CONCLUSIONS: The used
      examination model seems suitable, to examine qualitatively the development of the
      self in psychotic people. At a more comprehensive study it is necessary to
      shorten the duration of the interview and to carry out the evaluation directly of
      video or CD-ROM The result of the qualitative contents analysis showed obviously,
      in which categories the impeding effect on the development of a healthy self
      outweighed. This result supports the idea of an individualized multidimensional
      therapeutic concept, which supports the development of a healthy self. Out of
      this could surrender to consequences regarding an individual, multidimensional
      therapy which promotes the development of a healthy itself.

PMID- 18082110
TI  - [The "Werther-effect": legend or reality?].
AB  - In social sciences and in medicine, the term "Werther-effect" is used as a
      synonym for media induced imitation effects of suicidal behaviour. In Goethe s
      novel, the contemporary recipient could find a lot of details to identify with.
      One of these aspects is the detailed description of Werther s mental state, which
      suggests that suicidality plays a role in the novel a long time before the
      suicidal act at the end. Even though we find several reports on imitation effects
      connected to Goethe s Werther in literary works, the epidemiological extent of
      this phenomenon could never be determined. Also current social scientific
      research on the impact of suicide stories on suicidal behaviour could not
      completely remove the remaining lack of evidence of the phenomenon. Nevertheless,
      many studies support the hypothesis, that some aspects of quality of reporting
      could trigger short-term increases of suicides in certain population subgroups.
      In Austria, "Media Guidelines for Reporting on Suicides", have been issued to the
      media since 1987 as a suicide-preventive experiment. Since then, the aims of the
      experiment have been to reduce the numbers of suicides and suicide attempts in
      the Viennese subway and to reduce the overall suicide numbers. After the
      introduction of the media guidelines, the number of subway suicides and suicide
      attempts dropped more than 80% within 6 months. Since 1991, suicides plus suicide
      attempts - but not the number of suicides alone - have slowly and significantly
      increased. The increase of passenger numbers of the Viennese subway, which have
      nearly doubled, and the decrease of the overall suicide numbers in Vienna (-40%)
      and Austria (-33%) since mid 1987 increase the plausibility of the hypothesis,
      that the Austrian media guidelines have had an impact on suicidal behavior.

PMID- 18082111
TI  - [Sigmund Freud, Rudolf Meringer and Carl Mayer: slips of the tongue and mis
      readings. The history of a controversy].
AB  - In both his The Psychopathology of Everyday Life and his Lectures Sigmund Freud
      derived the terms unconscious, preconscious and conscious, particularly from
      slips in speech, slips in reading and forgetfulness. In these slips, Freud
      recognised parallels to dreams. In the work mentioned, he analysed these in depth
      as part of mental motivation. In the papers referred to, Sigmund Freud paid
      tribute to Rudolf Meringer and Carl Mayer's study which was published in 1895.
      Meringer and Mayer showed as phenomena reversals and rearrangement of whole
      words, syllables or sounds, along with pre-tones or anticipations and echoes,
      word contaminations and word substitutions as responsible for slips of the
      tongue. The present work demonstrates how passionately these three scientists
      have contributed to the controversy of their standpoints. For modern
      psycholinguistics and the psychology of language, speech errors are always an
      expression of a momentary malfunction of the human speech production system: for
      the cognitive process of speech production slips of the tongue offer an insight
      into speech processing. Pre-tones and echoes, serialization errors, as Meringer
      and Mayer recognised, represent the vast majority of slips of the tongue. They do
      not reveal any hidden point. But with lexical-semantic slips of the tongue the
      question of mental motivation is admissible. This short paper is a sign of
      appreciation and gratitude: firstly, a modest birthday gift for Sigmund Freud,
      secondly homage to Carl Mayer, who influenced generations of neurologists in his
      40 years of chairing the Psychiatric-Neurological Clinic in Innsbruck, so that
      Hans Ganner rightly spoke of a "Carl Mayer School". But lastly, this short study
      is also-and especially-a late recognition of Rudolf Meringer, the great Austrian
      linguist. The view an individual has concerning mental processes and the
      "topology of the psychic apparatus" is decisive as to the power of determination
      attached to the unconscious.

PMID- 18082112
TI  - Local cluster of psittacosis after bird show in the Netherlands, November 2007.

PMID- 18082113
TI  - AURES - the first Austrian report on antimicrobial resistance - perspective of
      the human sector.

PMID- 18082114
TI  - [Genes, forces and forms: mechanical aspects of prenatal craniofacial
      development].
AB  - Current knowledge of molecular signaling during craniofacial development is
      advancing rapidly. We know that cells can respond to mechanical stimuli by
      biochemical signaling. Thus, the link between mechanical stimuli and gene
      expression has become a new and important area of the morphological sciences.
      This field of research seems to be a revival of the old approach of developmental
      mechanics, which goes back to the embryologists His [36], Carey [13, 14], and
      Blechschmidt [5]. These researchers argued that forces play a fundamental role in
      tissue differentiation and morphogenesis. They understood morphogenesis as a
      closed system with living cells as the active part and biological, chemical, and
      physical laws as the rules. This review reports on linking mechanical aspects of
      developmental biology with the contemporary knowledge of tissue differentiation.
      We focus on the formation of cartilage (in relation to pressure), bone (in
      relation to shearing forces), and muscles (in relation to dilation forces). The
      cascade of molecules may be triggered by forces, which arise during physical cell
      and tissue interaction. Detailed morphological knowledge is mandatory to
      elucidate the exact location and timing of the regions where forces are exerted.
      Because this finding also holds true for the exact timing and location of
      signals, more 3D images of the developmental processes are required. Further
      research is also required to create methods for measuring forces within a tissue.
      The molecules whose presence and indispensability we are investigating appear to
      be mediators rather than creators of form.

PMID- 18082115
TI  - [Genetic origin of non-syndromic cleft lip and palate. TWIST, a candidate gene?
      Research protocol].
AB  - Non syndromic cleft lip and palate (CLP) is the most frequent human malformation.
      CLP is of complex inheritance and at least twenty contributing chromosomal
      regions have been identified by linkage studies. On the other hand, mutations in
      several genes such as TWIST and FGFR2 result in syndromic cranio-facial
      abnormalities of highly variable range. It is our hypothesis that some mutations
      at TWIST might contribute to CLP in absence of other dysmorphic features. Thus,
      DNA biopsies of patients with non syndromic CLP are collected and prepared to
      search for allelic variations or mutations at TWIST. This study should contribute
      to improve the classification of facial malformations relative to gene, to help
      to a better understanding of the inheritance pattern of this pathology, to help
      to genetic counselling for some cases aiming at the prevention of genetic
      disease. This project is based on a close cooperation between the Orthodontic
      Department, the Paediatric Surgery Department and the Center for Clinical
      Investigation (University Hospital in Strasbourg), in a joint project with an
      academic research laboratory, expert in molecular biology and genetics.

PMID- 18082116
TI  - [Odontometric data: applicability of Bolton's analysis to the people of Senegal].
AB  - One of the orthodontist's goals is to improve dental occlusion while taking into
      account dental, maxillary and facial balance. It is his responsibility, prior to
      any orthodontic treatment to make a positive and etiopathogenic diagnosis that
      will drive his treatment planning. One of the basic parameters to be considered
      is the mesiodistal width of the teeth. Indeed, a tooth size discrepancy often
      causes therapeutic failures; its diagnosis has been possible since 1958 thanks to
      Bolton whose researches were carried out on the American population. The
      principal objective of this study was to verify if his analysis is applicable to
      the Senegalese population. Its secondary objective was to specify the
      odontometric data of Senegalese subjects. For this reason, 60 Senegalese aged
      between 13 and 33 have been selected and for each subject we have measured the
      overjet and overbite, the mesiodistal and vestibulo-lingual diameters of the 12
      maxillary and mandibular teeth. The obtained results have allowed us to assume
      that the Bolton analysis can be applied to the Senegalese population as a whole.
      We have also found that the Senegalese subject's odontometric data did not have
      any significant difference with the known data.

PMID- 18082117
TI  - [Correlations between the volume of the sinuses and the facial bones and
      parameters of 3D cephalometry].
AB  - The goal of this work is to study, using a sample of 95 persons, the parameters
      of the 14 points of the 3D Treil cephalometric analysis and to compare them to
      the facial volumes of these subjects. The 3D parameters are described on three
      levels and for all three dimensions of space; they are also defined statistically
      for each class of occlusion, and indications are given for sagittal two
      dimensional variables. The correlations between all these variables and facial
      bones and air cavity volumes are also analyzed. The antero-posterior and vertical
      variables showed more statistically significant relationships with volumes than
      with transverse parameters. It appears that a Class III occlusion is primarily
      related to the vertical and antero-posterior position of the mandible and its
      morphology and not to its size, while Class II Division 1 types are associated
      with increased size of the maxillary sinuses. It also appears that facial hyper
      divergence is related to a decrease in the size of the maxilla and the mandible.

PMID- 18082118
TI  - [Interceptive treatment with the DAC appliance: structural analysis].
AB  - The aim of this retrospective short and middle term study was to evaluate dental
      and skeletal effects during early class II treatment. Thirty subjects were
      treated with DAC appliance, 32 children were not treated. Data were collected at
      the start of the study (t(1)), after the active treatment (t(1')) and 28 months
      after t(1) (t(2)). L.D.V. and Tweed cephalometric analyses were applied on the
      lateral roentgenograms of the three groups. Differences for all the variables
      from t(1) to t(1') and t(2) were calculated and compared by t-test. Results
      suggested that DAC appliance was able to achieve twice more mandibular growth in
      the treated group than in the non treated group. Anterior total skeletal and
      matricial rotations were similar to control group. Early DAC appliance achieved
      overjet correction thanks to major skeletal participation (89%) and little dental
      participation (11%). During following-up stage, overjet relapsed partially as
      shown in other articles with other appliances. As a conclusion, DAC appliance may
      be an orthopedic appliance indicated to achieve correction in class II skeletal
      pattern without maxillary prognathism and with mandibular retrognathism.

PMID- 18082119
TI  - [Evolution of orthodontic appliances from 1728 to 2007. Inaugural Conference of
      the 79th Scientific Meeting of the SFODF at Versailles, 31 May 2007].
AB  - The nature of orthodontic appliances depends, in part, on the development of
      therapeutic ideas and also on the materials and techniques that are available to
      practitioners. The first mechanisms appeared in 1728; they were attached to teeth
      by ligatures. Removable appliances, made of metal, ivory and, later, vulcanite
      developed as soon as practitioners became capable of taking reliable impressions,
      an epoch that began in 1840. A multiplicity of fixed appliances was introduced
      after the invention of a dental cement that could be used to attach them to teeth
      in 1871. But even before that, in 1860, dentists had begun to modify the form and
      the position of basal bone and to construct intra- and extra-oral appliances to
      accomplish this. And it wasn't until 1916 that Angle introduced the first bracket
      that allowed orthodontists to apply a couple of forces to teeth. For the most
      part, a new appliance didn't replace an older one. It was simply added to the
      armamentarium, which explains why we now have such a great diversity of systems
      at our disposal, and the imprecision of the indications for the use of many of
      them.

PMID- 18082120
TI  - [Validity of randomized clinical trials in evaluating the outcome of Class II
      treatments].
AB  - Despite on-going debates about their efficacy, functional appliances are still
      widely accepted and used by clinicians. According to the RCTs and their
      interpretations, the end result would be the same and you will not have more than
      2 mm of difference between different treatment modalities; however it has been
      repeatedly proven that there are significant variations between individuals in
      relation to their dental and skeletal changes and that is the most important
      common finding of all the studies in this field. This aspect of individual
      variation to treatment has to be considered and discussed in detail with patients
      and parents. We should not forget that the patient has 25% chance of obtaining a
      very good skeletal result and 25% chance of a very poor result or in between in
      50% of the cases, instead of basing our treatment decision on the averages.
      Despite extensive research including the RCTs in the area of Class II correction
      using different treatment modalities many questions remain unanswered. Future
      research in growth and genetics has the potential to clarify important points in
      patient selection and treatment outcome.

PMID- 18082123
TI  - An assay combining high-performance liquid chromatography and mass spectrometry
      to measure DNA interstrand cross-linking efficiency in oligonucleotides of
      varying sequences.
AB  - The main method of evaluating the DNA interstrand cross-linking ability of cancer
      chemotherapeutic agents in naked DNA currently involves the electrophoresis of
      relatively long radiolabeled duplex DNA fragments (typically approximately 2000
      bp) on neutral gels after incubation with the agent of interest. Denaturation by
      heating is carried out prior to loading, and a neutral gel allows reannealing of
      cross-linked DNA. To avoid the use of radioactivity we have developed a new
      method based on ion pair reversed phase liquid chromatography (RPLC) and mass
      spectrometry (MS) that allows characterization and quantitation of drug-DNA
      interstrand cross-links formed within short oligonucleotide duplexes (i.e., 12
      bp). Advantages of this assay include rapid throughput, as compared to
      electrophoretic methods, and the use of readily available short nonradiolabeled
      oligonucleotides of any sequence, thereby facilitating investigation of sequence
      selectivity. A further advantage is that all species separated by the
      chromatographic process can be positively identified by MS. Using this new
      method, we have investigated the rate of DNA cross-linking and sequence
      selectivity of the interstrand cross-linking agent SJG-136, a
      pyrrolobenzodiazepine (PBD) dimer currently in phase I clinical trials. The assay
      was found to be sufficiently sensitive and selective to allow separation of the
      unbound and drug-bound oligonucleotide species by high-performance liquid
      chromatography (HPLC) and to allow positive identification of these individual
      species by MS. A further benefit, as compared with electrophoretic methods, is
      that kinetic information can be obtained and compared for different binding
      sequences.

PMID- 18082124
TI  - A method to assess the lysosomal residence of proteins in cultured cells.
AB  - Analytical subcellular fractionation is playing an increasingly important role in
      proteomic studies to identify and validate components of cellular organelles. For
      lysosomes, definitive studies in this area have been restricted to rodent tissues
      due to technical constraints. Our goal was to design a quantitative assay that
      would allow clear demonstration of lysosomal localization in cultured human
      cells. We found that culturing HepG2 (human hepatocellular carcinoma) cells in
      progesterone-containing medium elicited an extensive shift in the buoyant density
      of lysosomes as measured by isopycnic centrifugation in sucrose density
      gradients. The density of other organelles remained essentially unchanged; thus,
      this shift represents a specific test for lysosomal localization. Progesterone
      treatment of a variety of other cultured cells also elicited a shift in lysosome
      density. This approach should represent a valuable tool for identification and
      validation of both luminal and membrane lysosomal proteins.

PMID- 18082125
TI  - Identification of ryanodine receptor 1 single-nucleotide polymorphisms by high
      resolution melting using the LightCycler 480 System.
AB  - High-resolution melting (HRM) allows single-nucleotide polymorphism (SNP)
      detection/typing using inexpensive generic heteroduplex-detecting double-stranded
      DNA (dsDNA) binding dyes. Until recently HRM has been a post-PCR process. With
      the LightCycler 480 System, however, the entire mutation screening process,
      including post-PCR analysis, can be performed using a single instrument. HRM
      assays were developed to allow screening of the ryanodine receptor gene (RYR1)
      for potential mutations causing malignant hyperthermia (MH) and/or central core
      disease (CCD) using the LightCycler 480 System. The assays were validated using
      engineered plasmids and/or genomic DNA samples that are either homozygous wild
      type or heterozygous for one of three SNPs that lead to the RyR1 amino acid
      substitutions T4826I, H4833Y, and/or R4861H. The HRM analyses were conducted
      using two different heteroduplex-detecting dsDNA binding dyes: LightCycler 480
      HRM dye and LCGreen Plus. Heterozygous samples for each of the HRM assays were
      readily distinguished from homozygous samples with both dyes. By using engineered
      plasmids, it was shown that even homozygous sequence variations can be identified
      by using either small amplicons or the addition of exogenous DNA after PCR. Thus,
      the LightCycler 480 System provides a novel, integrated, real-time PCR/HRM
      platform that allows high throughput, inexpensive SNP detection, and genotyping
      based on high-resolution amplicon melting.

PMID- 18082126
TI  - Development of an HPLC-MS/MS method for the selective determination of
      paracetamol metabolites in mouse urine.
AB  - An HPLC-MS/MS method has been developed for the selective quantitative analysis
      of paracetamol and its two major metabolites. The use of tandem MS enabled the
      detection and quantitation of metabolites in small sample sizes with high
      sensitivity and selectivity. Isocratic elution using acetonitrile and water
      containing formic acid combined with electrospray-tandem MS enabled the
      separation and accurate quantitation of each analyte and the internal standard 3
      acetamidophenol. The on-column limits of detection for paracetamol, paracetamol
      sulfate, and paracetamol glucuronide were 2.4, 1.2, and 1.2 pmol, respectively.
      The method was applied to quantitate paracetamol and its metabolites in mouse
      urine. It is highly specific, sensitive, and easily adaptable to measure these
      analytes in biological fluids of other animals.

PMID- 18082127
TI  - Differences in both matrix metalloproteinase 9 concentration and zymographic
      profile between plasma and serum with clot activators are due to the presence of
      amorphous silica or silicate salts in blood collection devices.
AB  - Matrix metalloproteinases (MMPs) are promising diagnostic tools, and blood
      sampling/handling alters MMP concentrations between plasma and serum and between
      serum with and without clot activators. To explain the higher MMP-9 expression in
      serum collected with clot accelerators relative to serum with no additives and to
      plasma, we analyzed the effects of increasing amounts of silica and silicates
      (components of clot activators) in citrate plasma, serum, and buffy coats
      collected in both plastic and glass tubes from 50 healthy donors, and we analyzed
      the effects of silica and silicate on cultured leukemia cells. The levels of MMP
      2 did not show significant changes between glass and plastic tubes, between serum
      and plasma, between serum with and without clot accelerators, or between silica
      and silicate treatments. No modification of MMP-9 expression was obtained by the
      addition of silica or silicate to previously separated plasma and serum.
      Increasing the amounts of nonsoluble silica and soluble silicate added to citrate
      and empty tubes prior to blood collection resulted in increasing levels of MMP-9
      relative to citrate plasma and serum. Silica and silicate added to buffy coats
      and leukemia cells significantly induced MMP-9 release/secretion, demonstrating
      that both silica and silicate induce the release of pro- and complexed MMP-9
      forms. We recommend limiting the misuse of serum and avoiding the interfering
      effects of clot activators.

PMID- 18082129
TI  - Uncoupling protein-2 accumulates rapidly in the inner mitochondrial membrane
      during mitochondrial reactive oxygen stress in macrophages.
AB  - Uncoupling protein-2 (UCP2) is a member of the inner mitochondrial membrane anion
      carrier superfamily. Although mRNA for UCP2 is widely expressed, protein
      expression is detected in only a few cell types, including macrophages. UCP2
      functions by an incompletely defined mechanism, to reduce reactive oxygen species
      production during mitochondrial electron transport. We observed that the
      abundance of UCP2 in macrophages increased rapidly in response to treatments
      (rotenone, antimycin A and diethyldithiocarbamate) that increased mitochondrial
      superoxide production, but not in response to superoxide produced outside the
      mitochondria or in response to H2O2. Increased UCP2 protein was not accompanied
      by increases in ucp2 gene expression or mRNA abundance, but was due to enhanced
      translational efficiency and possibly stabilization of UCP2 protein in the inner
      mitochondrial membrane. This was not dependent on mitochondrial membrane
      potential. These findings extend our understanding of the homeostatic function of
      UCP2 in regulating mitochondrial reactive oxygen production by identifying a
      feedback loop that senses mitochondrial reactive oxygen production and increases
      inner mitochondrial membrane UCP2 abundance and activity. Reactive oxygen species
      induction of UCP2 may facilitate survival of macrophages and retention of
      function in widely variable tissue environments.

PMID- 18082128
TI  - The role of rapid lipogenesis in insulin secretion: Insulin secretagogues acutely
      alter lipid composition of INS-1 832/13 cells.
AB  - Pancreatic beta cell mitochondria convert insulin secretagogues into products
      that support insulin exocytosis. We explored the idea that lipids are some of
      these products formed from acyl group transfer out of mitochondria to the
      cytosol, the site of lipid synthesis. There are two isoforms of acetyl-CoA
      carboxylase, the enzyme that forms malonyl-CoA from which C(2) units for lipid
      synthesis are formed. We found that ACC1, the isoform seen in lipogenic tissues,
      is the only isoform present in human and rat pancreatic islets and INS-1 832/13
      cells. Inhibitors of ACC and fatty acid synthase inhibited insulin release in
      islets and INS-1 cells. Carbon from glucose and pyruvate were rapidly
      incorporated into many lipid classes in INS-1 cells. Glucose and other insulin
      secretagogues acutely increased many lipids with C14-C24 chains including
      individual cholesterol esters, phospholipids and fatty acids. Many
      phosphatidylcholines and phosphatidylserines were increased and many
      phosphatidylinositols and several phosphatidylethanolamines were decreased. The
      results suggest that lipid remodeling and rapid lipogenesis from secretagogue
      carbon support insulin secretion.

PMID- 18082130
TI  - Dehydration-inducible changes in expression of two aquaporins in the sleeping
      chironomid, Polypedilum vanderplanki.
AB  - Aquaporin, AQP, is a channel protein that allows water to permeate across cell
      membranes. Larvae of the sleeping chironomid, Polypedilum vanderplanki, can
      withstand complete dehydration by entering anhydrobiosis, a state of suspended
      animation; however, the mechanism by which water flows out of the larval body
      during dehydration is still unclear. We isolated two cDNAs (PvAqp1 and PvAqp2)
      encoding water-selective aquaporins from the chironomid. When expressed in
      Xenopus oocytes, PvAQP1 and PvAQP2 facilitated permeation of water but not
      glycerol. Northern blots and in situ hybridization showed that expression of
      PvAqp1 was dehydration-inducible and ubiquitous whereas that of PvAqp2 was
      dehydration-repressive and fat body-specific. These data suggest distinct roles
      for these aquaporins in P. vanderplanki, i.e., PvAqp2 controls water homeostasis
      of fat body during normal conditions and PvAqp1 is involved in the removal of
      water during induction of anhydrobiosis.

PMID- 18082131
TI  - Growth-dependent effect of muscleblind knockdown on Caenorhabditis elegans.
AB  - The muscleblind-like (MBNL) proteins are tissue-specific alternative splicing
      regulators. Dysfunction of MBNL has been implicated in the pathogenesis of
      expanded CUG repeats-associated myotonic dystrophy (DM). In this study, we
      describe the identification and functional characterization of a Caenorhabditis
      elegans muscleblind (CeMbl) gene. CeMbl is a single gene alternatively spliced to
      generate two isoforms (CeMBL-A and CeMBL-B). It displays a high homology with
      human MBNL1 in the C3H1 zinc finger domains. CeMbl transcripts are detected in
      larval and adult stages. However, inactivation of CeMbl by RNA-mediated
      interference results in muscle phenotype only at adulthood. Immunofluorescence
      staining using anti-vinculin antibody reveals that the organization of dense body
      is disrupted in affected worms. Our results demonstrate a growth-dependent
      requirement of CeMbl on muscle structure and function. They also provide a
      possible molecular basis for the developmentally regulated toxicity of expanded
      CUG repeats.

PMID- 18082132
TI  - Differentiation-specific expression of chromatin remodeling factor BRM.
AB  - The chromatin remodeling complex SWI/SNF exclusively contains BRG1 or BRM as an
      ATPase subunit, but the physiological relevance of these ATPases is not yet
      clear. Here, we studied the developmental regulation of the brm gene. A
      differentiation-specific up-regulation of BRM expression was observed with P19,
      F9 and C2C12 cells as with neural cells and hepatocytes. The promoter region of
      brm contains two putative binding sites for CCAAT enhancer binding protein beta
      (C/EBPbeta). Each site partially overlapped with binding sites for GATAs.
      C/EBPbeta stimulated the transcriptional activity of the brm promoter but GATA2
      and 3 down-regulated the expression. C/EBPbeta bound to the proximal sequences of
      the promoter in differentiated cells and was replaced by GATAs which bound to the
      overlapping sites in the undifferentiated state. C/EBPbeta and GATAs may
      developmentally regulate the expression of brm by mutually exclusive binding.

PMID- 18082133
TI  - Structural changes of the regulatory proteins bound to the thin filaments in
      skeletal muscle contraction by X-ray fiber diffraction.
AB  - In order to clarify the structural changes related to the regulation mechanism in
      skeletal muscle contraction, the intensity changes of thin filament-based
      reflections were investigated by X-ray fiber diffraction. The time course and
      extent of intensity changes of the first to third order troponin (TN)-associated
      meridional reflections with a basic repeat of 38.4nm were different for each of
      these reflections. The intensity of the first and second thin filament layer
      lines changed in a reciprocal manner both during initial activation and during
      the force generation process. The axial spacings of the TN-meridional reflections
      decreased by approximately 0.1% upon activation relative to the relaxing state
      and increased by approximately 0.24% in the force generation state, in line with
      that of the 2.7-nm reflection. Ca(2+)-binding to TN triggered the shortening and
      a change in the helical symmetry of the thin filaments. Modeling of the
      structural changes using the intensities of the thin filament-based reflections
      suggested that the conformation of the globular core domain of TN altered upon
      activation, undergoing additional conformational changes at the tension plateau.
      The tail domain of TN moved together with tropomyosin during contraction. The
      results indicate that the structural changes of regulatory proteins bound to the
      actin filaments occur in two steps, the first in response to the Ca(2+)-binding
      and the second induced by actomyosin interaction.

PMID- 18082134
TI  - Commentary on H. Ide et al., "Tyk2 expression and its signaling enhances the
      invasiveness of prostate cancer cells".

PMID- 18082135
TI  - c-Jun amino terminal kinase 1 deficient mice are protected from streptozotocin
      induced islet injury.
AB  - In vitro studies have implicated the c-Jun amino terminal kinase (JNK) in
      cytokine-induced pancreatic injury leading to a loss of insulin production and
      hyperglycemia. We examined the role of JNK1 in the multiple low dose
      streptozotocin (MLD-STZ) model in which islet injury and hyperglycemia are
      dependent upon T cell immunity and pro-inflammatory cytokines. MLD-STZ in wild
      type mice induced islet leukocyte infiltration, cytokine production, beta-cell
      apoptosis, and hyperglycemia. In contrast, Jnk1-/- mice were substantially
      protected from a loss of insulin producing cells and hyperglycemia in the MLD-STZ
      model despite a marked islet T cell and macrophage infiltrate. Based upon several
      lines of evidence, this protection was attributed to a reduction in TNF-alpha
      production by infiltrating Jnk1-/- macrophages leading to reduced beta-cell
      apoptosis. In conclusion, JNK1 signaling plays an essential role in macrophage
      induced beta-cell apoptosis and the development of hyperglycemia in MLD-STZ
      induced pancreatic injury.

PMID- 18082136
TI  - Ecotoxicology of ozone: bioactivation of extracellular ascorbate.
AB  - The ascorbate pools of the extracellular respiratory lining fluids and the plant
      apoplast are currently considered as part of the first line of defence against
      ambient ozone. Ozone is in fact rapidly decomposed by ascorbate, but the only
      product identified so far (singlet oxygen) is toxic. Peroxy-l-threonic and peroxy
      oxalic acids are now derived as further decomposition products on the basis of
      Criegee-type ozone chemistry. These secondary toxicants may resemble known ozone
      induced transmitter molecules by participating in signalling events affecting
      plant and animal innate immunity.

PMID- 18082137
TI  - Mitochondrial dysfunction is a possible cause of accelerated senescence of
      mesothelial cells exposed to high glucose.
AB  - High glucose has been found to accelerate cell senescence in vitro. The exact
      mechanism of this effect is, however, still poorly understood. In this paper we
      show that human peritoneal mesothelial cells (HPMCs) propagated under high (30mM)
      glucose were characterized by higher density of DNA double-strand breaks than
      cells exposed to standard (5mM) glucose concentration. Under both low and high
      glucose conditions, the vast majority of DNA damage localized to non-telomeric
      regions of the genome. Moreover, exposure to high glucose resulted in increased
      accumulation of lipofuscin, increased production of superoxides and peroxides as
      well as reduced mitochondrial membrane potential and increased mitochondrial
      mass. Treatment of cells with the free radical scavenger PBN partially rescued
      the premature senescence caused by high glucose. Together, these results indicate
      that high glucose may accelerate senescence of HPMCs by impairing mitochondrial
      function, resulting in overproduction of reactive oxygen species and extensive
      DNA damage.

PMID- 18082138
TI  - Beta-trace protein is not superior to cystatin C for the estimation of GFR in
      patients receiving corticosteroids.
AB  - OBJECTIVES: Comparison of the effect of corticosteroid therapy on the diagnostic
      performance of cystatin C (Cys) and beta-trace protein (bTP), two endogenous
      markers of GFR. DESIGN AND METHODS: Out of a total of 193 pediatric inulin
      clearance studies, a random sample of 85 steroid-free studies served to establish
      GFR prediction equations (eGFR), which were used to compare the remaining 76
      steroid-free and 32 steroid-positive studies (median prednisone dose 33.0 mg m(
      2) day(-1)). RESULTS: We found a positive relationship between prednisone dose
      and eGFR(betaTP) (b=0.414, p=0.0002) and a negative relationship with eGFR(cys)
      (b=-0.208, p=0.0091). Only Cys independently predicted GFR below 90 mL min(-1)
      1.73 m(-2), both in steroid-positives (b=6.260, p=0.010) and steroid-negatives
      (b=6.845, p=0.012). Glucocorticoid therapy did not affect the accuracy in
      estimating GFR within 30% of measured GFR for Cys, while accuracy was lower with
      bTP (65.6% vs. 81.6%, p=0.08). CONCLUSION: Glucocorticoids have less impact on
      the diagnostic accuracy of Cys than bTP.

PMID- 18082139
TI  - Rapid and simple detection of a mycobacterium circulating antigen in serum of
      pulmonary tuberculosis patients by using a monoclonal antibody and Fast-Dot
      ELISA.
AB  - OBJECTIVES: Several immunoassays have been established for detection of
      Mycobacterium tuberculosis (MTB) antigens in serum, sputum and cerebrospinal
      fluid of tuberculous patients using polyclonal or monoclonal antibodies raised
      against different mycobacterium antigens. Some of these assays display both high
      sensitivity and specificity for the detection of these antigens. However, these
      assays require special and highly expensive equipment and the procedures require
      long periods for their completion. Thus, the rationale of this study was to
      establish and evaluate Fast-Dot-Enzyme-Linked Immunosorbent Assay (FD-ELISA) as a
      fast, cheap and field applicable assay for detection of mycobacterium antigen in
      serum of patients with pulmonary TB. DESIGNS AND METHODS: This study included
      three groups: group I: 175 tuberculous patients with pulmonary TB proves with
      sputum Ziehl-Neelsen (ZN) for acid-fast bacilli and sputum culture (all cases
      were culture positive for MTB); Group II: 65 patients with diseases other than
      pulmonary TB as bronchial carcinoma (17 patients), bronchial asthma (29 patients)
      and chronic obstructive pulmonary disease (19 patients); group III: 50 healthy
      individuals. Groups II and III served as negative control groups. The target
      mycobacterium antigen was identified in both crude mycobacterium antigens extract
      and serum of patients with pulmonary TB, using western blotting technique and
      anti-TB monoclonal antibody (TB20-mAb) and then it was estimated in the serum
      samples of all studied groups as an index of tuberculosis, using a newly
      developed FD-ELISA. RESULTS: The target mycobacterium antigen was identified at
      20 kDa molecular mass in crude mycobacterium antigens extract as well as in serum
      of patients with pulmonary TB. The developed FD-ELISA detected the mycobacterium
      antigen in the sera of 159 out of 175 pulmonary TB patients with a sensitivity of
      90.8% and 93.0% positive predictive value (PPV). In addition, it identified 12
      false weakly positive cases out of 115 samples of negative control groups (7 out
      of 65 non-TB patients and 5 out of 50 healthy individuals) with a specificity of
      89.6% and 86.6% negative predictive value (NPV). Standardization of the FD-ELISA
      using a serial dilution of the purified mycobacterium antigen indicated that the
      assay was able to detect 1.8 microg/ml as a lowest detectable antigen
      concentration. CONCLUSIONS: The newly developed FD-ELISA is a simple, rapid and
      highly sensitive assay for detection of mycobacterium antigen in patients with
      pulmonary TB. Moreover, all steps were performed at room temperature and without
      the need to use expensive equipment, and this may enhance the application of this
      assay in tuberculosis screening programs. Further study is needed for
      confirmation of FD-ELISA reproducibility in light infected pulmonary TB patients
      and in a large population.

PMID- 18082141
TI  - Catalase T and Cu,Zn-superoxide dismutase in the acetic acid-induced programmed
      cell death in Saccharomyces cerevisiae.
AB  - To investigate the role of catalase and superoxide dismutase (SOD) in the acetic
      acid (AA) induced yeast programmed cell death (AA-PCD), we compared Saccharomyces
      cerevisiae cells (C-Y) and cells individually over-expressing catalase T (CTT1-Y)
      and Cu,Zn-SOD (SOD1-Y) with respect to cell survival, hydrogen peroxide (H2O2)
      levels and enzyme activity as measured up to 200 min after AA treatment. AA-PCD
      does not occur in CTT1-Y, where H2O2 levels were lower than in C-Y and the over
      expressed catalase activity decreased with time. In SOD1-Y, AA-PCD was
      exacerbated; high H2O2 levels were found, SOD activity increased early, remaining
      constant en route to AA-PCD, but catalase activity was strongly reduced.

PMID- 18082140
TI  - Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced
      osteoblastic differentiation.
AB  - NELL1 is an extracellular protein inducing osteogenic differentiation and bone
      formation of osteoblastic cells. To elucidate the intracellular signaling cascade
      evoked by NELL1, we have shown that NELL1 protein transiently activates the MAPK
      signaling cascade, induces the phosphorylation of Runx2, and promotes the rapid
      intracellular accumulation of Tyr-phosphorylated proteins. Unlike BMP2, NELL1
      protein does not activate the Smad signaling cascade. These findings suggest that
      upon binding to a specific receptor NELL1 transduces an osteogenic signal through
      activation of certain Tyr-kinases associated with the Ras-MAPK cascade, and
      finally leads to the osteogenic differentiation.

PMID- 18082142
TI  - Structure-guided engineering of the coenzyme specificity of Pseudomonas
      fluorescens mannitol 2-dehydrogenase to enable efficient utilization of NAD(H)
      and NADP(H).
AB  - The structure of Pseudomonas fluorescens mannitol 2-dehydrogenase with bound NAD+
      leads to the suggestion that the carboxylate group of Asp(69) forms a bifurcated
      hydrogen bond with the 2' and 3' hydroxyl groups of the adenosine of NAD+ and
      contributes to the 400-fold preference of the enzyme for NAD+ as compared to
      NADP+. Accordingly, the enzyme with the Asp(69)-->Ala substitution was found to
      use NADP(H) almost as well as wild-type enzyme uses NAD(H). The Glu(68)-->Lys
      substitution was expected to enhance the electrostatic interaction of the enzyme
      with the 2'-phosphate of NADP+. The Glu(68)-->Lys:Asp(69)-->Ala doubly mutated
      enzyme showed about a 10-fold preference for NADP(H) over NAD(H), accompanied by
      a small decrease in catalytic efficiency for NAD(H)-dependent reactions as
      compared to wild-type enzyme.

PMID- 18082143
TI  - TRPA1 channel activation induces cholecystokinin release via extracellular
      calcium.
AB  - TRPA1 channels are non-selective cation channels activated by plant derived
      pungent products including allyl isothiocyanate (AITC) from mustard. Therefore,
      possible intestinal secretory functions of these channels were investigated. We
      detected TRPA1 mRNA in mouse and human duodenal mucosa and in intestinal mouse
      neuroendocrine STC-1 cells. Stimulation of STC-1 cells with AITC increased
      intracellular calcium ([Ca(2+)](i)) and significantly stimulated cholecystokinin
      secretion by 6.7-fold. AITC induced cholecystokinin release was completely
      blocked by TRPA1 antagonist ruthenium red and depletion of extracellular calcium
      and reduced by 36% by nimodipine and nifedipine. This suggests that spices in our
      daily food might stimulate digestive functions.

PMID- 18082144
TI  - Arabidopsis HY5 protein functions as a DNA-binding tag for purification and
      functional immobilization of proteins on agarose/DNA microplate.
AB  - Protein microarray is considered to be one of the key analytical tools for high
      throughput protein function analysis. Here, we report that the Arabidopsis HY5
      functions as a novel DNA-binding tag (DBtag) for proteins. We also demonstrate
      that the DBtagged proteins could be immobilized and purified on a newly designed
      agarose/DNA microplate. Furthermore, we show three applications using the
      microarray: (1) detection of autophosphorylation activity of DBtagged human
      protein kinases and inhibition of their activity by staurosporine, (2) specific
      cleavage of DBtagged proteins by a virus protease and caspase 3, and (3)
      detection of a protein-protein interaction between the DBtagged UBE2N and UBE2v1.
      Thus, this method may facilitate rapid functional analysis of a wide range of
      proteins.

PMID- 18082145
TI  - Prion protein structure is affected by pH-dependent interaction with membranes: a
      study in a model system.
AB  - Interaction of full length recombinant hamster prion protein with liposomes
      mimicking lipid rafts or non-raft membrane regions was studied by circular
      dichroism, chemical cross-linking and sucrose gradient ultracentrifugation. At pH
      7.0, the protein bound
      palmitoyloleoylphosphatidylcholine/cholesterol/sphingomyelin/monosialoganglioside
      GM1 (GM1) ganglioside liposomes but not palmitoyloleoylphosphatidylcholine alone
      (bound/free=0.33 and 0.01, respectively), maintaining the native alpha-helical
      structure and monomeric form. At pH 5.0, though still binding to quaternary
      mixtures, in particular GM1, the protein bound also to
      palmitoyloleoylphosphatidylcholine (bound/free 0.35) becoming unfolded and
      oligomeric. The pH-dependent interaction with raft or non-raft membranes might
      have implication in vivo, by stabilizing or destabilizing the protein.

PMID- 18082146
TI  - Toll-like receptor 4 and cytokine expression involved in functional immune
      response in an originally established porcine intestinal epitheliocyte cell line.
AB  - To study the immune responses of porcine intestinal epithelial cells to gram
      negative bacteria via toll-like receptors (TLRs), originally established porcine
      intestinal epitheliocyte (PIE) cells were treated with lipopolysaccharide (LPS)
      or swine-specific enterotoxigenic Escherichia coli (ETEC). Real-time quantitative
      PCR revealed that PIE cells expressed TLR1-9 and MD-2 mRNAs, preferentially
      expressed TLR4/MD-2. Immunostaining of PIE cells revealed that TLR4 was precisely
      expressed in PIE cells at the protein level. PIE cells treated with LPS had up
      regulated expression of several TLRs (TLR2, 3, 4, 5 and 8), type 1 helper T (Th1)
      cytokines (interleukin (IL)-1alpha, IL-1beta, IL-6, IL-15, 18, leukemia
      inhibitory factor (LIF), and interferon (IFN)-beta), and chemokines (monocyte
      chemoattractant protein (MCP)-1 and IL-8). ETEC enhanced the expression of TLR2,
      Th1 type cytokines (IL-1alpha, IL-12p35 and IL-6) and chemokines (MCP-1 and IL
      8). These results indicate that PIE induces inflammatory responses by up
      regulating Th1 cytokines and chemokines in response to LPS or ETEC, suggesting
      that PIE is a useful cell line for studying inflammatory responses via TLR4/MD-2
      in intestinal epithelial cells.

PMID- 18082147
TI  - Proteases as modulators of tumor-stromal interaction: primary tumors to bone
      metastases.
AB  - As cells undergo oncogenic transformation and as malignant cells arrive at
      metastatic sites, a complex interplay occurs with the surrounding stroma. This
      dialogue between the tumor and stroma ultimately dictates the success of the
      tumor cells in the given microenvironment. As a result, understanding the
      molecular mechanisms at work is important for developing new therapeutic
      modalities. Proteases are major players in the interaction between tumor and
      stroma. This review will focus on the role of proteases in modulating tumor
      stromal interactions of both primary breast and prostate tumors as well as at
      bone metastatic sites in a way that favors tumor growth.

PMID- 18082148
TI  - Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary
      radioprotection.
AB  - Development of radiation therapy (RT)-induced lung injury is associated with
      chronic production of reactive oxygen and nitrogen species (ROS/RNS). MnTE-2
      PyP5+ is a catalytic Mn porphyrin mimic of SOD, already shown to protect lungs
      from RT-induced injury by scavenging ROS/RNS. The purpose of this study was to
      compare MnTE-2-PyP5+ with a newly introduced analogue MnTnHex-2-PyP5+, which is
      expected to be a more effective radioprotector due to its lipophilic properties.
      This study shows that Fischer rats which were irradiated to their right
      hemithorax (28 Gy) have less pulmonary injury as measured using breathing
      frequencies when treated with daily subcutaneous injections of MnTE-2-PyP5+ (3
      and 6 mg/kg) or MnTnHex-2-PyP5+ (0.3, 0.6, or 1.0 mg/kg) for 2 weeks after RT.
      However, at 16 weeks post-RT, only MnTE-2-PyP5+ at a dose of 6 mg/kg is able to
      ameliorate oxidative damage, block activation of HIF-1alpha and TGF-beta, and
      impair upregulation of CA-IX and VEGF. MnTnHex-2-PyP5+ at a dose of 0.3 mg/kg is
      effective only in reducing RT-induced TGF-beta and CA-IX expression. Significant
      loss of body weight was observed in animals receiving MnTnHex-2-PyP5+ (0.3 and
      0.6 mg/kg). MnTnHex-2-PyP5+ has the ability to dissolve lipid membranes, causing
      local irritation/necrosis at injection sites if given at doses of 1 mg/kg or
      higher. In conclusion, both compounds show an ability to ameliorate lung damage
      as measured using breathing frequencies and histopathologic evaluation. However,
      MnTE-2-PyP5+ at 6 mg/kg proved to be more effective in reducing expression of key
      molecular factors known to play an important role in radiation-induced lung
      injury.

PMID- 18082149
TI  - Ischemic preconditioning of the rat retina: protective role of ferritin.
AB  - Ischemic preconditioning (IPC) of the retina, accomplished by ischemia of short
      duration, is highly effective in preventing subsequent severe injury caused by
      iron-dependent free radical burst after prolonged ischemia. To investigate the
      mechanistic basis for IPC rescue, we examined changes in the levels of the
      retinal redox-active and labile iron pool, ferritin, and ferritin-bound iron.
      Prolonged ischemia severely impaired retinal function, with total loss of the
      full-field electroretinographic response. IPC provided marked protection against
      such injury. Histological examination revealed that ischemia-associated
      structural damage and loss of cells in the outer and inner nuclear layers were
      largely prevented by IPC. Ferritin levels decreased after prolonged ischemia but
      remained close to normal when the ischemic episode was preceded by IPC. The
      protective effect of IPC on retinal function and ferritin was blocked by a zinc
      desferrioxamine complex known to interfere with iron signaling. The results
      suggest a mechanism whereby IPC activates an iron signaling pathway leading to a
      marked increase in ferritin levels, which mediates resistance to prolonged
      ischemia.

PMID- 18082150
TI  - Detection of local polarity and conformational changes at the active site of
      rabbit muscle creatine kinase with a new arginine-specific fluorescent probe.
AB  - A new polarity-sensitive fluorescent probe, 3-(4-chloro-6-p-glyoxal-phenoxy-1,3,5
      triazinylamino)-7-(dimethylamino)-2-methylphenazine (CGTDP), is synthesized for
      selective labeling of active-site arginine residues. The probe comprises a
      neutral red moiety as a polarity-sensitive fluorophore and a phenylglyoxal unit
      as an arginine-specific labeling group. The probe exhibits a sensitive response
      of shift of fluorescence maximum emission wavelength to solvent polarity only
      instead of pH or temperature, which leads to the use of the probe in detecting
      the local polarity and conformational changes of the active site of rabbit muscle
      creatine kinase (CK) denatured by pH or temperature. The polarity of the active
      site domain has been first found to correspond to a dielectric constant of about
      44, and the conformational change of the active site directly revealed by CGTDP
      occurs far before that of CK as a whole disclosed by the intrinsic tryptophan
      fluorescence during acid or thermal denaturation. The present strategy may
      provide a useful method to detect the local polarity and conformational changes
      of the active sites of many enzymes that employ arginine residues as anion
      recognition sites under different denaturation conditions.

PMID- 18082151
TI  - Proteomic analysis of mouse islets after multiple low-dose streptozotocin
      injection.
AB  - The islets of Langerhans are scattered throughout the pancreas and play a major
      role in the control of metabolic fuel homeostasis. To get a better understanding
      of the mechanisms underlying type 1 diabetes mellitus, we have generated a mouse
      model by injections of multiple low-dose streptozotocin. The islets in the mouse
      pancreas were handpicked and proteins from the islets were then isolated and
      separated by two-dimensional gel electrophoresis. Seven proteins were found to be
      altered significantly at expression level. Among the seven proteins, four were up
      regulated and three were down-regulated in diabetic mice as compared with
      controls. These proteins were successfully identified by matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry and the changes of
      selected protein expression were further validated by quantitative real time PCR
      and Western blotting. Voltage-dependent anion-selective channel protein 1 and
      peroxiredoxin-4 were found for the first time to be associated with type 1
      diabetes mellitus in mouse islets in the current study. These results suggest
      that glucose transport, beta cell proliferation/death, and oxidative stress play
      important roles in maintaining the balance of glucose level. Our study also
      provides novel insight into the mechanism of type 1 diabetes mellitus.

PMID- 18082152
TI  - Human CpG binding protein interacts with MLL1, MLL2 and hSet1 and regulates Hox
      gene expression.
AB  - Human encodes several histone H3-Lysine 4 (H3K4) specific methyl-transferases
      (HMTs) such as MLL1 (mixed lineage leukemia 1), MLL2, MLL3, hSet1 etc, that play
      critical roles in gene expression. These HMTs are present as distinct multi
      protein complexes with several proteins in common. Herein, we have affinity
      purified and characterized human CpG binding protein (CGBP) and its interacting
      proteins from human cells. We demonstrated that CGBP is co-purified with three
      H3K4 specific HMTs MLL1, MLL2, and hSet1. We also performed independent immuno
      precipitation of MLL1, MLL2 and hSet1 complexes from human cell and demonstrated
      that each of these complexes contains CGBP. In addition, CGBP is co-localized
      with MLL1, MLL2 and hSet1 in vivo and binds to the promoter of MLL target gene
      HoxA7. Antisense mediated knock down of CGBP diminished the recruitment of MLL1
      and down regulated levels of H3K4 trimethylation in HoxA7 promoter affecting its
      expression. These results demonstrated that CGBP interacts with MLL1, MLL2 as
      well as hSet1 HMTs and plays critical roles in regulations of MLL target genes.

PMID- 18082153
TI  - Profound challenges do remain in our understanding of the mechanisms of gene
      regulation.

PMID- 18082154
TI  - Characterization of a neuregulin-1 gene promoter: positive regulation of type I
      isoforms by NF-kappaB.
AB  - The neuregulin-1 (Nrg1) gene encodes for a group of growth factors with multiple
      functions during mammalian development. Overexpression of Nrg1 is found in many
      different cancer types and correlates with cancer progression and an aggressive
      phenotype. In this study we identified the promoter of Nrg1 type I isoforms.
      Reporter gene assays revealed that 850 bp upstream from the translation
      initiation codon are necessary for high transcriptional activity in murine Neuro
      2A neuroblastoma cells. The core promoter is highly conserved among mammals, has
      multiple transcription start sites and is located in a CpG island. The conserved
      promoter region contains GC-and GT-box elements and overexpression of Sp1
      increased promoter activity, while ZBP-89 decreased the activity. Overexpression
      of the NF-kappaB subunit p65 (RelA) led to a strong activation of the promoter
      mediated through a single NF-kappaB binding site. Reflecting that the
      transcriptional activity of NF-kappaB and Sp1 are increased upon Nrg-stimulation
      in breast cancer cells this study suggests a potential mechanism of a positive
      feedback loop/autoregulation of neuregulin.

PMID- 18082155
TI  - Semifluorinated alkanes--primitive surfactants of fascinating properties.
AB  - Semifluorinated alkanes (SFAs) are diblock molecules, in which two mutually
      immiscible moieties, namely the hydrocarbon segment and the perfluorinated
      segment are bound covalently. The presence of two opposing segments within one
      molecule makes semifluorinated alkanes a very interesting class of compounds,
      which show a particular behavior both in bulk and at interfaces. Their highly
      asymmetric structure, arising from the incompatibility of the both constituent
      parts, results in surface activity of these molecules (so-called primitive
      surfactants) when dissolved in organic solvents, and allows for the Langmuir
      monolayer formation if spread at the air/water interface, despite of the absence
      of any polar group. Since 1984 (when SFAs have been characterized for the first
      time by Rabolt et al. [Rabolt JF, Russell TP, Twieg RJ. Macromolecules
      1984;17:2786]), semifluorinated alkanes have been subjected to many studies. The
      present article reviews the results obtained so far and covers the aspects of
      their synthesis, properties in bulk (solutions and solid state) and applications.
      Special emphasis is put on the Langmuir monolayer properties and self
      organization of SFAs on solid substrates.

PMID- 18082156
TI  - [Amyloid goiter: first sign of systemic amyloidosis].
AB  - Although amyloid infiltration of the thyroid gland is an uncommon but well-known
      phenomenon, the appearance of a goiter secondary to amyloid deposits is rare. The
      goiter enlarges rapidly and progressively, often becoming compressive like
      thyroid cancer. The diagnosis is rarely suggested clinically even in the presence
      of known amyloidosis. We describe the case of a 45-year-old patient who presented
      an amyloid goiter as the first manifestation of systemic amyloidosis, probably
      secondary to bronchiectasis.

PMID- 18082157
TI  - How do people apprehend large numerosities?
AB  - People discriminate remarkably well among large numerosities. These
      discriminations, however, need not entail numerical representation of the
      quantities being compared. This research evaluated the role of both non-numerical
      and numerical information in adult judgments of relative numerosity for large
      numerosity spatial arrays. Results of Experiment 1 indicated that judgments of
      relative numerosity were affected by the amount of open space in the arrays being
      compared. Further, the accuracy of verbal estimates of the numerosities of the
      arrays made upon completion of the comparison task bore little relation to
      performance on that task. Experiment 2, however, showed that numerical estimates
      for individually presented arrays were affected in much the same way by open
      space within or around the edges of the array as were the comparative judgments
      examined in Experiment 1. The findings suggest that adults heuristically utilize
      non-numerical cues as well as numerical information in apprehending large
      numerosities.

PMID- 18082159
TI  - Cell rearrangement and cell division during the tissue level morphogenesis of
      evaginating Drosophila imaginal discs.
AB  - The evagination of Drosophila imaginal discs is a classic system for studying
      tissue level morphogenesis. Evagination involves a dramatic change in morphology
      and published data argue that this is mediated by cell shape changes. We have
      reexamined the evagination of both the leg and wing discs and find that the
      process involves cell rearrangement and that cell divisions take place during the
      process. The number of cells across the width of the ptc domain in the wing and
      the omb domain in the leg decreased as the tissue extended during evagination and
      we observed cell rearrangement to be common during this period. In addition,
      almost half of the cells in the region of the leg examined divided between 4 and
      8 h after white prepupae formation. Interestingly, these divisions were not
      typically oriented parallel to the axis of elongation. Our observations show that
      disc evagination involves multiple cellular behaviors, as is the case for many
      other morphogenetic processes.

PMID- 18082158
TI  - Squid, Cup, and PABP55B function together to regulate gurken translation in
      Drosophila.
AB  - During Drosophila melanogaster oogenesis, the proper localization of gurken (grk)
      mRNA and protein is required for the establishment of the dorsal-ventral axis of
      the egg and future embryo. Squid (Sqd) is an RNA-binding protein that is required
      for the correct localization and translational regulation of the grk message. We
      show that Cup and polyA-binding protein (PABP) interact physically with Sqd and
      with each other in ovaries. We show that cup mutants lay dorsalized eggs, enhance
      dorsalization of weak sqd alleles, and display defects in grk mRNA localization
      and Grk protein accumulation. In contrast, pAbp mutants lay ventralized eggs and
      enhance grk haploinsufficiency. PABP also interacts genetically and biochemically
      with Encore. These data predict a model in which Cup and Sqd mediate
      translational repression of unlocalized grk mRNA, and PABP and Enc facilitate
      translational activation of the message once it is fully localized to the dorsal
      anterior region of the oocyte. These data also provide the first evidence of a
      link between the complex of commonly used trans-acting factors and Enc, a factor
      that is required for grk translation.

PMID- 18082161
TI  - Cardiovascular effects of L-glutamate injected in the medial prefrontal cortex of
      spontaneously hypertensive rats.
AB  - We have previously reported that l-glutamate (L-glu) injected into the ventral
      portion of medial prefrontal cortex (vMPFC) of unanesthetized normotensive Wistar
      rats elicited cardiovascular responses. In the present study we investigated
      whether the spontaneously hypertensive rat (SHR) exhibit abnormal cardiovascular
      responses after L-glu microinjection in the vMPFC. Microinjections of L-glu (3,
      9, 27, 81 or 150 nmol/200 nl) caused long-lasting dose-related depressor and
      bradycardiac responses in unanesthetized SHR (n=6, each dose). Pressor and
      tachycardiac responses were evoked after the injection of 81 nmol of L-glu in the
      vMPFC of normotensive Wistar rats (n=6). Systemic pretreatment with the beta1
      adrenoceptor antagonist atenolol (1.5 mg/kg, i.v.) had no effect on L-glu
      cardiovascular responses evoked in the SHR (n=5). However, the treatment with the
      muscarinic antagonist homatropine methyl bromide (1 mg/kg, i.v.) blocked the
      bradycardiac response to L-glu, without significant effects on depressor response
      evoked by L-glu in the SHR (n=5). These results indicate that the bradycardiac
      response to the injection of L-glu injection in the vMPFC is due to activation of
      the parasympathetic system and not to inhibition of the cardiac sympathetic
      input. In conclusion, results indicate opposite cardiovascular responses when L
      glu was microinjected in the vMPFC of unanesthetized SHR or normotensive. The
      bradycardiac response observed in the SHR was due to parasympathetic activation
      and was not affected by pharmacological blockade of the cardiac sympathetic
      output.

PMID- 18082160
TI  - 5-Fluorotryptamine is a partial agonist at 5-HT3 receptors, and reveals that size
      and electronegativity at the 5 position of tryptamine are critical for efficient
      receptor function.
AB  - Antagonists, but not agonists, of the 5-HT3 receptor are useful therapeutic
      agents, and it is possible that partial agonists may also be potentially useful
      in the clinic. Here we show that 5-fluorotryptamine (5-FT) is a partial agonist
      at both 5-HT3A and 5-HT3AB receptors with an Rmax (Imax/Imax 5-HT) of 0.64 and
      0.45 respectively. It is about 10 fold less potent than 5-HT: EC50=16 and 27
      microM, and Ki for displacement of [3H]granisetron binding=0.8 and 1.8 microM for
      5-HT3A and 5-HT3AB receptors respectively. We have also explored the potencies
      and efficacies of tryptamine and a range of 5-substituted tryptamine derivatives.
      At 5-HT3A receptors tryptamine is a weak (Rmax=0.15), low affinity (EC50=113
      microM; Ki=4.8 microM) partial agonist, while 5-chlorotryptamine has a similar
      affinity to 5-FT (EC50=8.1 microM; Ki=2.7 microM) but is a very weak partial
      agonist (Rmax=0. 0037). These, and data from 5-methyltryptamine and 5
      methoxytryptamine, reveal the importance of size and electronegativity at this
      location for efficient channel opening.

PMID- 18082162
TI  - Antimalarial quinolones: synthesis, potency, and mechanistic studies.
AB  - In the present article we examine the antiplasmodial activities of novel
      quinolone derivatives bearing extended alkyl or alkoxy side chains terminated by
      a trifluoromethyl group. In the series under investigation, the IC50 values
      ranged from 1.2 to approximately 30 nM against chloroquine-sensitive and
      multidrug-resistant Plasmodium falciparum strains. Modest to significant cross
      resistance was noted in evaluation of these haloalkyl- and haloalkoxyquinolones
      for activity against the atovaquone-resistant clinical isolate Tm90-C2B,
      indicating that a primary target for some of these compounds is the parasite
      cytochrome bc1 complex. Additional evidence to support this biochemical mechanism
      includes the use of oxygen biosensor plate technology to show that the quinolone
      derivatives block oxygen consumption by parasitized red blood cells in a fashion
      similar to atovaquone in side-by-side experiments. Atovaquone is extremely potent
      and is the only drug in clinical use that targets the Plasmodium bc1 complex, but
      rapid emergence of resistance to it in both mono- and combination therapy is
      evident and therefore additional drugs are needed to target the cytochrome bc1
      complex which are active against atovaquone-resistant parasites. Our study of a
      number of halogenated alkyl and alkoxy 4(1H)-quinolones highlights the potential
      for development of "endochin-like quinolones" (ELQ), bearing an extended
      trifluoroalkyl moiety at the 3-position, that exhibit selective antiplasmodial
      effects in the low nanomolar range and inhibitory activity against chloroquine
      and atovaquone-resistant parasites. Further studies of halogenated alkyl- and
      alkoxy-quinolones may lead to the development of safe and effective therapeutics
      for use in treatment or prevention of malaria and other parasitic diseases.

PMID- 18082163
TI  - Prenatal antibiotic treatment does not decrease group B streptococcus
      colonization at delivery.
AB  - OBJECTIVE: To evaluate whether an outpatient antibiotic regimen decreased group B
      streptococcal (GBS) colonization to preclude the use of intrapartum antibiotics.
      METHODS: A double-blind randomized controlled trial evaluating prenatal oral
      amoxicillin versus placebo with the primary outcome of GBS colonization at the
      time of labor. RESULTS: Of those patients receiving both amoxicillin and a repeat
      culture at the time of labor, 6 of the 14 (43%) tested positive for GBS
      colonization. Given persistent GBS colonization of 67% (10/15) in the placebo
      group, treatment with amoxicillin did not significantly impact colonization at
      the time of delivery (P=0.20). CONCLUSION: A regimen of outpatient amoxicillin
      was associated with persistent GBS colonization in 43% of women at the time of
      labor. Oral prenatal antibiotic prophylaxis against GBS does not sufficiently
      reduce colonization to preclude intrapartum intravenous antibiotics.

PMID- 18082164
TI  - Complications of loop ileostomy and ileostomy closure and their implications for
      extended enterostomal therapy: a prospective clinical study.
AB  - INTRODUCTION: Patients who have a temporary loop ileostomy have impaired quality
      of life. Complications associated with a loop ileostomy or ileostomy closure will
      impair patients' quality of life further and require extended enterostomal
      therapy. We performed a prospective audit of loop ileostomy to ascertain the
      nature of the workload that may be created with ileostomy-related complications.
      PATIENTS AND METHODS: One hundred and forty patients (67 males, 73 females,
      median age 50 years, range 5-90 years) who received a temporary loop ileostomy
      were analysed after completion of proformas on a prospective basis between 1999
      and 2006. RESULTS: Operation was performed for rectal cancer 100 (71%), familial
      adenomatous polyposis 14 (10%), ulcerative colitis 21 (15%) and for trauma or
      Hirchsprung's disease 5 (3%). Complications of loop ileostomy were: retraction 1
      (0.7%), ileostomy flux 11 (8%), stomal prolapse 1 (0.7%), parastomal hernia 1
      (0.7%), paraileostomy abscess 4 (3%) and severe skin excoriation 9 (6%). The loop
      ileostomy was reversed in 117 (83%) at a median (range) of 13 weeks (1-60).
      Ileostomy closure-related complications were: small bowel fistula 1 (0.9%), small
      bowel obstruction 5 (4.3%) and a stitch sinus in 1 (0.9%). Five women developed
      recto-vaginal fistula (n=3; 2.6%), pouch-vaginal fistula (n=1; 0.9%) and pouch
      anal fistula (n=1; 0.9%) that required extended enterostomal therapy, after loop
      ileostomy reversal. CONCLUSION: Nineteen percent of patients following creation
      of a loop ileostomy and 10.5% of patients after reversal of the ileostomy
      required extended enterostomal care by a specialized enterostomal therapist,
      which supported resumption of a normal life.

PMID- 18082165
TI  - Variability of the impact transient during repeated barefoot walking trials.
AB  - Most studies of human gait assume that the normal gait patterns are consistent
      and therefore that it is adequate to assess the baseline condition once. However,
      recent research has brought this assumption into question. The purpose of this
      study is to evaluate the repeatability of components of the ground reaction
      force, peak force loading rate and percent of ground reaction force at impact
      above 60Hz, across repeated walking trials throughout the experiment. Twenty-two
      subjects walked barefoot 10 times across a force platform interspersed between
      trial blocks of three different shod conditions. We used traditional grouped data
      analysis (ANOVA) as well as a more novel single-subject analysis. The grouped
      analysis revealed one statistically significant comparison between barefoot
      trials for the root mean square greater than 60Hz variable. The single-subject
      analysis revealed that approximately 5% of the barefoot trials were significantly
      different for each of the peak force loading rate and percent of impact transient
      signal above 60Hz variables. We suggest that these results, from both data
      analysis techniques, are not biologically relevant because the magnitudes of most
      of the changes were not large enough to have a biological significance (peak
      force loading rate differences less than 50%, and less than 0.05-fold differences
      in the percent of the ground reaction force above 60Hz). In conclusion, our data
      suggest that baseline impact force measurements during walking are stable and do
      not need to be recorded between experimental conditions in walking studies.

PMID- 18082166
TI  - Trunk density profile estimates from dual X-ray absorptiometry.
AB  - Accurate body segment parameters are necessary to estimate joint loads when using
      biomechanical models. Geometric methods can provide individualized data for these
      models but the accuracy of the geometric methods depends on accurate segment
      density estimates. The trunk, which is important in many biomechanical models,
      has the largest variability in density along its length. Therefore, the
      objectives of this study were to: (1) develop a new method for modeling trunk
      density profiles based on dual X-ray absorptiometry (DXA) and (2) develop a trunk
      density function for college-aged females and males that can be used in geometric
      methods. To this end, the density profiles of 25 females and 24 males were
      determined by combining the measurements from a photogrammetric method and DXA
      readings. A discrete Fourier transformation was then used to develop the density
      functions for each sex. The individual density and average density profiles
      compare well with the literature. There were distinct differences between the
      profiles of two of participants (one female and one male), and the average for
      their sex. It is believed that the variations in these two participants' density
      profiles were a result of the amount and distribution of fat they possessed.
      Further studies are needed to support this possibility. The new density functions
      eliminate the uniform density assumption associated with some geometric models
      thus providing more accurate trunk segment parameter estimates. In turn, more
      accurate moments and forces can be estimated for the kinetic analyses of certain
      human movements.

PMID- 18082167
TI  - The villi contribute to the mechanics in the guinea pig small intestine.
AB  - Previous studies have shown that intestinal mucosa is compressed in vivo. The
      present study investigated the contribution of the mucosal villi to the
      biomechanical properties in circumferential direction in the guinea pig jejunum.
      Eight 20-cm-long jejunal segments were excised and each separated into two 10-cm
      long segments. The mucosal villi were scraped off from half the segments. The
      segments were pressurized in vitro with Krebs solution from 0-10cmH(2)O using a
      ramp distension protocol with simultaneous diameter recordings. Circumferential
      stresses and strains were computed from the diameter, pressure and the zero
      stress state data. Removing the villi resulted in small opening angles (139+/-16
      degrees vs 189+/-27 degrees with villi) and small absolute values of residual
      strain (inner: -0.05+/-0.03 vs -0.33+/-0.06 with villi; outer: 0.11+/-0.04 vs
      0.33+/-0.08 with villi) (P<0.001). The outer diameter as a function of the
      pressure did not differ between jejunal segments with villi and without villi.
      The average mid-wall stress-strain curve without villi was shifted to the left
      compared to the segment with villi, indicating the wall was stiffer without
      villi. However, if the stress-strain computation for the segments with villi was
      referenced to the zero-stress state of the segments without villi, the curve was
      only partly shifted to the left. In conclusion, this paper provides the first
      direct experimental evidence that the villi are important for the biomechanical
      properties of guinea pig small intestine in circumferential direction, because
      the villi not only affect the zero-stress state configuration but also partially
      affect the stress-strain distribution in the intestinal wall. Therefore, the
      villi should be taken into account in the analysis of biomechanical properties of
      the intestinal wall.

PMID- 18082168
TI  - Modeling the kinetics of cell membrane spreading on substrates with ligand
      density gradient.
AB  - An analytical model is developed for the effect of surface gradient in ligand
      density on the adhesion kinetics of a curved elastic membrane with mobile
      receptors. The displacement and speed of spreading at the edge of adhesion zone
      as well as the density profile of receptors along the membrane are predicted as a
      function of time. According to results, in the diffusion-controlled regime, the
      front edge displacement of adhesion zone and the rate of membrane spreading
      decreased with increasing the ligand density in a certain direction. Furthermore,
      the displacement of the edge of the adhesion zone did not scale with the square
      root of time, as observed on substrates with uniform ligand density.

PMID- 18082169
TI  - Monodisperse, hypercrosslinked polymer microspheres as tailor-made sorbents for
      highly efficient solid-phase extractions of polar pollutants from water samples.
AB  - In this detailed analytical study, we have evaluated in-house synthesised
      polymeric solid-phase extraction (SPE) sorbents in the form of monodisperse,
      hypercrosslinked polymer microspheres with diameters in the low micrometre range
      (approximately 4 microm). More specifically, their performance in the on-line SPE
      of a group of polar pollutants has been investigated thoroughly. The novel
      hypercrosslinked materials were compared with satisfactory results to commercial
      SPE sorbents with similar chemical and morphological properties, albeit that the
      commercial materials had higher particle sizes and broader particle size
      distributions. The on-line SPE method developed using these novel particles as
      packing material was applied successfully to ultrapure, mineral, tap and Ebre
      river water samples, with near total recoveries of all the analytes studied when
      500 ml samples were percolated through the sorbents. Method validation with river
      water samples demonstrated good linearity, low detection limits as well as
      satisfactory precision in terms of repeatability and reproducibility, with values
      of relative standard deviation (%RSD) lower than 6.7 and 8.7%, respectively.

PMID- 18082170
TI  - Optimized method avoiding solvent-induced response enhancement in the analysis of
      volatile and semi-volatile polyfluorinated alkylated compounds using gas
      chromatography-mass spectrometry.
AB  - A method for the analysis of airborne (semi-)volatile polyfluorinated alkyl
      substances (PFASs) was optimized to avoid solvent-induced response enhancements
      as observed using ethyl acetate as extraction solvent (recoveries up to 300%,
      likely due to acetic acid as impurity). Of nine solvents tested, only the use of
      acetone, dichloromethane, methyl tert-butyl ether, and acetone:petroleum ether
      (1:1, v/v) resulted in recoveries below 100% and acetone:methyl tert-butyl ether
      (1:1, v/v) was chosen as suited extraction solvent. An appropriate GC capillary
      column and the application of mass-labelled internal standards appeared to be
      essential for these analyses. Instrumental limits of detection of <0.2 pg
      (dimethylperfluoroocatanesulfonamide, ethyl-[(2)H(5)]perfluorooctanesulfonamide,
      methyl-[(2)H(3)]perfluorooctanesulfonamide) to 8.2 pg
      (perfluorooctanesulfonamide) and LOQ of 0.4 pg
      (dimethylperfluoroocatanesulfonamide, ethyl-[(2)H(5)]perfluorooctanesulfonamide,
      methyl-[(2)H(3)]perfluorooctanesulfonamide) to 16.4 pg
      (perfluorooctanesulfonamide) were determined.

PMID- 18082171
TI  - Comprehensive two-dimensional gas chromatography for enhanced analysis of
      naphthas: new column combination involving permethylated cyclodextrin in the
      second dimension.
AB  - A new column association using comprehensive two-dimensional gas chromatography
      for the detailed molecular analysis of hydrocarbon mixtures is reported in this
      paper. In order to compare the impact of two different secondary columns, a novel
      column combination relying on a GC x 2GC system was used. This system is based on
      a non-polar first column (PONA) combined with both a permethylated beta
      cyclodextrin (beta-Dex 120) stationary phase and a polysilphenylensiloxane (BPX
      50) in the second dimension. Compared to BPX 50 stationary phase, the
      implementation of beta-cyclodextrin columns as the second dimension was found to
      improve the resolution between paraffins and naphthenes in the naphtha range but
      not in the middle distillate range. Attempts to improve the results and to
      understand the interaction mechanism remained unsuccessful. Therefore, the
      benefits of the beta-Dex 120-column are only demonstrated on heavy naphtha cut
      for the quantitation of hydrocarbons.

PMID- 18082172
TI  - Purification by centrifugal partition chromatography of amphiphilic compounds,
      glycolipids and pseudo-glycolipids synthesized by using cells.
AB  - Centrifugal partition chromatography (CPC) was applied to separate amphiphilic
      glycolipids and pseudo-glycolipids synthesized by using cells. Neutral and acidic
      lipid fractions were isolated by CPC under suitable conditions respectively.
      Separation of neutral lipid, Gb3-type and Gb4-type oligosaccharide synthesized by
      using cells, was performed with a two-phase solvent system composed of chloroform
      methanol-water at a volume ratio of 5:6:4. On the other hand, separation of
      acidic lipid, GM3-type oligosaccharide synthesized by using cells, and
      ganglioside extracted from rat brain were performed with a two-phase solvent
      system composed of butanol-ethanol-1% acetic acid at a volume ratio of 4:1:5.
      8.3mg of Gb3 analogue, 5.1mg of Gb4 analogue, and 19.5mg of GM3 analogue were
      purified from 3.2l of culture medium obtained by incubation of African green
      monkey kidney (Vero) cells with 50 microM n-dodecyl beta-lactoside using CPC.

PMID- 18082173
TI  - Polanyi-based models for the adsorption of naphthalene from aqueous solutions
      onto nonpolar polymeric adsorbents.
AB  - In this research, naphthalene was adopted as the representative model compound of
      PAHs, and static adsorption of naphthalene from aqueous solution onto three
      commercial polymeric adsorbents with different pore structure was investigated.
      Nonlinear isotherms models, i.e., Freundlich, Langmuir, and Polanyi-Dubinin-Manes
      (PDM) models were tested to fit experimental data, and the experimental data were
      found to fit well by the PDM model. Through both isotherm modeling and
      constructing "characteristic curve," Polanyi theory was useful to describe the
      adsorption process of naphthalene by polymeric adsorbents, providing evidence
      that a micropore filling phenomenon was involved during the adsorption process.
      In addition, a good linear correlation was obtained between the naphthalene
      adsorption capacities and the micropore volume of adsorbents (Vmicro), whereas no
      linear relationship was found between the naphthalene adsorption capacities and
      the specific surface area of adsorbents. Based on the PDM model, the micropore
      volumes of adsorbents was introduced to normalize the equilibrium adsorbed volume
      (qv), plots of qv/V(micro) vs adsorption potential density for naphthalene on
      three different polymeric adsorbents were collapsed to a single correlation
      curve, which would be of great benefit to predict the adsorption capacity of
      adsorbent for the purpose of adsorption engineering design.

PMID- 18082174
TI  - Investigation on the assembled structure-property correlation of supramolecular
      hydrogel formed from low-molecular-weight gelator.
AB  - The investigation on structure-property correlation is important for
      understanding the gelating mechanism of supramolecular hydrogels. In this paper,
      a low-molecular-weight hydrogelator (termed as gelator 1) prepared from 1,2,4,5
      benzene tetracarboxylic acid (BTA) and 4-hydroxy pyridine (PHP) was able to gel
      water effectively. The influence of environmental stimulation, such as cooling
      speed and ultrasonic treatment, on the structure of the assembling fibers and the
      macroscopic properties of the gels was investigated via multiple techniques. The
      results indicated that the fiber size decreased as increasing the cooling speed
      and the smallest fibers were obtained under ultrasonic treatment. As the fibers
      became smaller, the gel with higher T(gel), lower bonded water content and higher
      dynamic modulus was obtained. Therefore it is possible to control the gel
      performances via the environmental stimulation. The relationship between the
      assembled structure and properties is helpful for understanding the gel formation
      mechanism and makes the gels suitable for different applications.

PMID- 18082175
TI  - In situ growth of nanogold on quartz crystal microbalance and its application in
      the interaction between heparin and antithrombin III.
AB  - A novel biosensor for detecting antithrombin III (AT III) was constructed based
      on in situ growth of nanogold on the gold electrode of quartz crystal
      microbalance (QCM). The growth process of nanogold was monitored by QCM in real
      time. Heparin was used as the affinity ligand and immobilized onto the nanogold
      modified gold electrode. A flow injection analysis-quartz crystal microbalance
      (FIA-QCM) system was used to investigate the relationship between nanogold growth
      and the AT III response. Along with the nanogold particle growth within initial 5
      min, the amount of heparin immobilized onto the nanogold modified electrode
      increased quickly. Correspondingly, the frequency response to AT III binding
      increased rapidly at the same time. After that, both the immobilized amount of
      heparin and the sensor response to AT III decreased gradually. Compared with the
      directly immobilized large nanogold particles, the in situ grown particles with
      the same size occupy more sensor surface, resulting in higher frequency shifts to
      AT III in the interaction study between heparin and AT III. The obtained
      constants of AT III binding to immobilized heparin are k(ass)=(1.65+/-0.12)x10(3)
      L/mols, k diss=(2.63+/-0.18)x10(-2) 1/s and K(A)=(6.27+/-0.42)x10(4) L/mol.

PMID- 18082176
TI  - Design and synthesis of ordered mesoporous silica materials with high degree of
      silica condensation at high temperature from a mixture of polymer surfactant with
      small organic ammonium.
AB  - Thermal stability on a mixture of triblock polymer (P123) and fluorocarbon
      surfactant (FC-4) in acidic media for synthesis of ordered mesoporous materials
      has been carefully investigated by NMR spectroscopy at various treated
      temperatures (RT-180 degrees C) and the templating mechanism of the mixture on
      high-temperature synthesis has been proposed. Accordingly, we have designed
      fluorocarbon-free templates for syntheses of ordered mesoporous silica materials
      at high temperatures. As expected, ordered mesoporous silica materials with high
      degree of silica condensation are synthesized at high temperatures from these
      designed templates.

PMID- 18082177
TI  - Structural characterization of U(VI) surface complexes on kaolinite in the
      presence of humic acid using EXAFS spectroscopy.
AB  - To determine the influence of humic acid (HA), pH, and presence of atmospheric
      CO2 on the sorption of U(VI) onto kaolinite, the structure of the surface
      complexes was studied by U L III-edge extended X-ray absorption fine structure
      (EXAFS) spectroscopy. The best fits to the experimental EXAFS data were obtained
      by including two uranium coordination shells with two axial (O ax) and five
      equatorial (O eq) oxygen atoms at 1.77+/-0.02 and 2.34+/-0.02 A, respectively,
      and two coordination shells with one Al/Si atom each at 3.1 and 3.3 A. As in the
      case of the binary system U(VI)-kaolinite, uranium forms inner-sphere surface
      complexes by edge sharing with aluminum octahedra and/or silicon tetrahedra. HA
      and atmospheric CO2 as well as pH had no influence on the EXAFS structural
      parameters in the pH range of 5-8. Despite the presence of HA, U(VI) prefers to
      sorb directly onto kaolinite and not to HA that is bound to the clay surface. X
      ray photoelectron spectroscopy (XPS) measurements of kaolinite particles that had
      been exposed to HA suspensions showed that significant parts of the kaolinite
      surface are not covered by HA.

PMID- 18082178
TI  - A one-step aqueous synthetic route to extremely small CdSe nanoparticles.
AB  - By employing Na2Se as a selenium source, we demonstrate that extremely small (
      approximately 1 nm) mercapto acid-stabilized CdSe nanoparticles can be
      conveniently prepared in water. The as-prepared nanoparticles start to show
      dominant near band-gap photoluminescence in the blue spectral range and show high
      photoluminescence in the green spectral range.

PMID- 18082179
TI  - Surface-modified carbon black for As(V) removal.
AB  - This paper reports the results of the adsorption performance of As(V) removal by
      a commercial carbon black and its H2SO4-modified form in a single-ion situation.
      The influence of different process parameters and the physicochemical principles
      involved were studied in detail. Acid modification caused morphological changes
      in the virgin carbon black as evidenced by BET surface area measurements and SEM
      study. FTIR spectra showed the introduction of sulfonic acid group in the parent
      carbon due to H2SO4 treatment. TGA analysis revealed higher weight loss
      characteristics of the modified carbon, demonstrating the creation of functional
      groups. The point of zero charge (pH pzc) of the modified carbon black is highly
      acidic (3.5) compared to commercial carbon black (6.4). It directly infers the
      generation of acidic functional moieties in the carbon black. The adsorption
      experiments were carried out following batch equilibrium techniques. The kinetics
      and thermodynamics of adsorption were investigated to unveil the mechanism and
      nature of the adsorption process, respectively. The kinetic parameters of
      different models were calculated and discussed. The kinetics of adsorption can be
      expressed by a pseudo-second-order model and intraparticle diffusion was not the
      rate-determining step. Dependence of pH on adsorption showed maximum metal uptake
      in the range of 4-5 and inferred surface complexion as the principal mechanism of
      adsorption. The equilibrium adsorption data were modeled using Freundlich,
      Langmuir, and Dubinin-Kaganer-Radushkevich (DKR) isotherm equations and the
      corresponding isotherm parameters were calculated and discussed in detail.

PMID- 18082180
TI  - In crystallo capture of a Michaelis complex and product-binding modes of a
      bacterial phosphotriesterase.
AB  - The mechanism by which the binuclear metallophosphotriesterases (PTEs, E.C.
      3.1.8.1) catalyse substrate hydrolysis has been extensively studied. The mu
      hydroxo bridge between the metal ions has been proposed to be the initiating
      nucleophile in the hydrolytic reaction. In contrast, analysis of some biomimetic
      systems has indicated that mu-hydroxo bridges are often not themselves
      nucleophiles, but act as general bases for freely exchangeable nucleophilic water
      molecules. Herein, we present crystallographic analyses of a bacterial PTE from
      Agrobacterium radiobacter, OpdA, capturing the enzyme-substrate complex during
      hydrolysis. This model of the Michaelis complex suggests the alignment of the
      substrate will favour attack from a solvent molecule terminally coordinated to
      the alpha-metal ion. The bridging of both metal ions by the product, without
      disruption of the mu-hydroxo bridge, is also consistent with nucleophilic attack
      occurring from the terminal position. When phosphodiesters are soaked into
      crystals of OpdA, they coordinate bidentately to the beta-metal ion, displacing
      the mu-hydroxo bridge. Thus, alternative product-binding modes exist for the
      PTEs, and it is the bridging mode that appears to result from phosphotriester
      hydrolysis. Kinetic analysis of the PTE and promiscuous phosphodiesterase
      activities confirms that the presence of a mu-hydroxo bridge during
      phosphotriester hydrolysis is correlated with a lower pK(a) for the nucleophile,
      consistent with a general base function during catalysis.

PMID- 18082181
TI  - Alpha-synuclein selectively binds to anionic phospholipids embedded in liquid
      disordered domains.
AB  - Previous studies indicate that binding of alpha-synuclein to membranes is
      critical for its physiological function and the development of Parkinson's
      disease (PD). Here, we have investigated the association of fluorescence-labeled
      alpha-synuclein variants with different types of giant unilamellar vesicles using
      confocal microscopy. We found that alpha-synuclein binds with high affinity to
      anionic phospholipids, when they are embedded in a liquid-disordered as opposed
      to a liquid-ordered environment. This indicates that not only electrostatic
      forces but also lipid packing and hydrophobic interactions are critical for the
      association of alpha-synuclein with membranes in vitro. When compared to wild
      type alpha-synuclein, the disease-causing alpha-synuclein variant A30P bound less
      efficiently to anionic phospholipids, while the variant E46K showed enhanced
      binding. This suggests that the natural association of alpha-synuclein with
      membranes is altered in the inherited forms of Parkinson's disease.

PMID- 18082182
TI  - Hypomanic, cyclothymic and hostile personality traits in bipolar spectrum
      illness: a family-based study.
AB  - OBJECTIVES: To examine hypomanic, cyclothymic and hostile personality traits in a
      large, euthymic, family-based group of individuals with bipolar disorder (BPD)
      and their affectively ill and healthy relatives. To test whether these traits
      follow a distribution with the most "pathological" scores in the bipolar disorder
      I (BPD I) group and the least "pathological" scores in the unaffected relatives.
      METHODS: Two-hundred and ninety-six individuals from 47 bipolar disorder families
      were administered a battery of personality questionnaires (Temperament Evaluation
      of Memphis, Pisa, Paris, and San Diego; Temperament and Character Inventory;
      Affective Neuroscience Personality Scale; Hypomanic Personality Scale; Borderline
      Traits Questionnaire) as well as a self-rating depression (Beck Depression
      Inventory) and mania (Altman Self-Rating Mania) scale. Out of the 296
      participants, 57 were diagnosed with BPD I, 24 with bipolar disorder II (BPD II),
      58 with recurrent major depression (MDE-R), 45 had one previous depressive
      episode (MDE-S), and 86 were unaffected. Twenty six individuals had another DSM
      IV diagnosis. RESULTS: The BPD I group displayed elevated hypomanic, cyclothymic
      and hostile traits. These traits were also characteristic of the BPD II group but
      were less salient in the MDE-R group. The MDE-S group did not differ
      significantly from unaffected relatives. Hypomanic personality characteristics
      were clearly elevated in both BPD groups and differentiated BPD from major
      depressive disorder (MDD) individuals. CONCLUSIONS: Our results provide
      preliminary support for the hypothesis that temperament is a genetically
      quantitative trait.

PMID- 18082183
TI  - Pure alexia for kana. Characterization of alexia with lesions of the inferior
      occipital cortex.
AB  - OBJECTIVE: To characterize reading impairments caused by lesions in the posterior
      occipital cortices. METHODS: We gave six patients with these lesions reading and
      writing tests and located a critical site for alexia using MRI and SPECT.
      RESULTS: The patients read three-character kana (Japanese syllabograms) nonwords,
      and five-character kana nonwords significantly or at a near significant level
      more poorly and slowly than normal subjects, whereas they read kanji (Japanese
      morphograms) almost correctly but more slowly. Letter-by-letter reading with a
      single-kana character identification impairment (in five patients), a word-length
      effect, kinesthetic facilitation, a lexicality effect, and minor to mild agraphia
      for kanji (in three patients) were observed. These deficits were characteristic
      of pure alexia. Alexia disappeared within a few months except in one patient who
      had extensive hypoperfusion in the left occipital lobe. A shared lesion was
      located in the left posterior fusiform/inferior occipital gyri (Area 18/19) on
      MRI, and there was blood flow reduction around this area on SPECT. This area
      coincided with the activation site for kana word covert reading in our previous
      study. CONCLUSIONS: These results suggest that pure alexia particularly for kana,
      or more generally pure alexia for letters, is caused by a lesion in the posterior
      inferior occipital cortex, characterized primarily by impaired kana character or
      letter identification, with relatively preserved kanji or word recognition.

PMID- 18082193
TI  - Tadalafil increases Akt and extracellular signal-regulated kinase 1/2 activation,
      and prevents apoptotic cell death in the penis following denervation.
AB  - PURPOSE: Despite techniques to preserve the cavernous nerves during radical
      prostatectomy erectile dysfunction remains a complication. We determined whether
      bilateral cavernous nerve resection induces apoptosis in the penis. We also
      determined whether treatment with the phosphodiesterase-5 inhibitor tadalafil
      prevents apoptosis as well as the specific mechanisms involved. MATERIALS AND
      METHODS: Mice were subjected to cavernous nerve resection or sham surgery.
      Penises were processed for the identification of apoptotic cells, changes in
      phosphorylation of several protein kinases and immunolocalization of specific
      kinases. Mice were also placed on tadalafil or vehicle after cavernous nerve
      resection and the penises were processed as described. Statistical analysis was
      performed with the Mann-Whitney U test for comparisons among groups or Student's
      t test. RESULTS: An increase in apoptotic cavernous smooth muscle and endothelial
      cells was evident by 2 weeks, which further increased 4 and 6 weeks after
      cavernous nerve resection. Apoptosis coincided with an increase in the
      phosphorylation of c-jun N-terminal kinase and p38 mitogen activated protein
      kinase. Phospho-c-jun N-terminal kinase was immunolocalized to endothelial and
      smooth muscle cells. Treatment with tadalafil decreased the number of apoptotic
      cells and increased the phosphorylation of the 2 survival associated kinases Akt
      and extracellular signal-regulated kinase 1/2. CONCLUSIONS: These results provide
      a rationale for the early use of phosphodiesterase-5 inhibition following radical
      prostatectomy or extensive pelvic surgery, during which there may be injury to
      the cavernous nerves, to aid in the return of erectile function.

PMID- 18082194
TI  - Pubo-urethral ligament transection causes stress urinary incontinence in the
      female rat: a novel animal model of stress urinary incontinence.
AB  - PURPOSE: We hypothesized that transection of the pubo-urethral ligament in the
      female rat would cause stress urinary incontinence, as indicated by decreased
      leak point pressure. We created a novel model of pubo-urethral ligament
      deficiency in the rat and validated our model through comparison with an
      established model of stress urinary incontinence. MATERIALS AND METHODS: A total
      of 21 female age matched Sprague-Dawley rats (Harlan, Indianapolis, Indiana) were
      randomly assigned to 5 groups, including pubo-urethral ligament transection or
      sham pubo-urethral ligament transection with leak point pressure measured 4 days
      (groups 1 and 2) or 10 days (groups 3 and 4) postoperatively and bilateral
      pudendal nerve transection with leak point pressure measured 4 days
      postoperatively (group 5). Leak point pressure was measured in all groups via a
      suprapubic catheter. The Wilcoxon signed rank test was used to evaluate
      differences between the groups. RESULTS: Leak point pressure was significantly
      decreased in the pubo-urethral ligament transection groups compared to that in
      the sham treated groups after 4 days (mean +/- SEM 16.3 cm +/-2.74 vs 36.6 +/-
      8.39 cm H(2)O, p <0.00001), although it was no different from that in the
      pudendal nerve transection group (14.5 +/- 1.06 cm H(2)O, p <0.44). Ten days
      after surgery leak point pressure remained significantly lower in the pubo
      urethral ligament transection groups compared to that in the sham treated groups
      (17.6 +/- 6.36 vs 31.2 +/- 5.14 cm H(2)O, p <0.00001), indicating the durability
      of pubo-urethral ligament transection for inducing stress urinary incontinence in
      female rats. CONCLUSIONS: Our results demonstrate that deficiency of the pubo
      urethral ligament in the female rat induces stress urinary incontinence
      comparable to that in a previously established model of pudendal nerve
      transection induced stress urinary incontinence. This novel rat model could be
      used to investigate the mechanisms of urethral hypermobility in female stress
      urinary incontinence or potential therapeutic interventions for stress urinary
      incontinence.

PMID- 18082195
TI  - Mechanisms by which a phytotherapeutic drug influences bladder activity in rats.
AB  - PURPOSE: We investigated the mechanisms by which Eviprostat, a phytotherapeutic
      drug for benign prostatic hyperplasia, influences bladder activity in rats.
      MATERIALS AND METHODS: A total of 42 female rats were divided into a control
      group and an Eviprostat group. Rats in the control group were fed a standard
      diet, while animals in the Eviprostat group were fed a diet containing 0.1%
      Eviprostat. After 2 weeks 14 rats (7 rats per group) underwent continuous
      cystometry with physiological saline or 0.1% acetic acid solution and bladder
      activity was recorded. Body weight, blood pressure, plasma monoamines and
      adenosine triphosphate were measured in another 14 rats (7 per group). In the
      remaining 14 rats (7 per group) 0.1% acetic acid solution was infused into the
      bladder and urinary adenosine triphosphate was measured before and after
      stimulation. RESULTS: During cystometry with acetic acid the interval between
      bladder contractions was shorter and maximum bladder contraction pressure was
      higher in the control group compared with results obtained using physiological
      saline but such differences were not seen in the Eviprostat group. Plasma
      adrenaline and noradrenaline were lower in the Eviprostat group than the control
      group but no difference in blood pressure was observed. Urinary adenosine
      triphosphate was higher in the 2 groups than before stimulation but the increase
      was smaller in the Eviprostat group than in the control group. CONCLUSIONS: These
      results suggest that Eviprostat acts to maintain low catecholamine and also
      inhibit pathological bladder activity by decreasing adenosine triphosphate
      release from the bladder.

PMID- 18082196
TI  - Abnormal expression of differentiation related proteins and proteoglycan core
      proteins in the urothelium of patients with interstitial cystitis.
AB  - PURPOSE: Expression of the proteoglycan core proteins biglycan, decorin, perlecan
      and syndecan-1, and differentiation related markers of keratins 18 and 20 were
      examined to determine the origins of the loss of the glycosaminoglycan layer and
      investigate more fully the altered differentiation of the urothelium in
      interstitial cystitis. MATERIALS AND METHODS: Formalin fixed biopsies from 27
      patients with interstitial cystitis and 5 controls were immunohistochemically
      labeled for the described proteins and scored using a modification of previous
      scoring for other markers. Inflammation was scored from hematoxylin and eosin
      stained slides. By combining previous with new data, cluster analysis showed the
      relationships among the markers and samples. RESULTS: Interstitial cystitis
      specimens clustered into 4 groups, ranging from most biomarkers abnormal to most
      biomarkers normal, but all clustered separately from normal controls. One group
      of interstitial cystitis specimens mainly showed aberrant expression of E
      cadherin, which might represent an early abnormality. The biomarkers fell into 2
      major groupings. One group consisted of chondroitin sulfate, perlecan, biglycan,
      decorin and the tight junction protein ZO-1. A second cluster consisted of
      uroplakin, the epithelial marker keratin 18 and 20, and the morphology of the
      layer. E-cadherin and syndecan-1 showed little relation to the other 2 clusters
      or to each other. Inflammation correlated moderately with syndecan-1 but to no
      other marker. CONCLUSIONS: Findings strongly suggest abnormal differentiation in
      the interstitial cystitis urothelium with a loss of barrier function markers and
      altered differentiation markers being independent and occurring independently of
      inflammation. Loss of the glycosaminoglycan layer was associated with a loss of
      biglycan and perlecan on the luminal layer.

PMID- 18082197
TI  - Bacterial cystitis is accompanied by increased peripheral thermal sensitivity in
      mice.
AB  - PURPOSE: Visceral inflammation and pain associated with chemical cystitis produce
      increased sensitivity to noxious stimuli in the sacral dermatomes. We determined
      whether a similar sensitization occurs in response to bacterial cystitis.
      MATERIALS AND METHODS: Bacterial cystitis was induced by intravesical
      instillation of Escherichia coli 1677 in female C57BL/6N and C3H/OuJ mice
      (Jackson Laboratories, Bar Harbor, Maine). C3H/HeJ mice (Jackson Laboratories)
      served as a control because C3H/HeJ mice lack functional toll-like receptor 4,
      which is an essential component of cellular recognition of bacterial
      lipopolysaccharide. Hind paw sensitivity to thermal stimulus was quantitatively
      determined 1, 2, 7 and 14 days after infection. RESULTS: Intravesical
      instillation of E. coli produced infection in all strains of mice. Infection
      persisted in all C3H/OuJ and C3H/HeJ mice but it spontaneously cleared in some
      C57BL/6N mice. Increased sensitivity to thermal stimuli was observed in C57BL/6N
      and C3H/OuJ mice starting 1 to 2 days after E. coli instillation and it was still
      present 14 days after instillation. Increased sensitivity to thermal stimuli did
      not occur in C3H/HeJ mice. CONCLUSIONS: E. coli induced cystitis produced
      increased sensitivity to peripheral thermal stimuli in mice with competent toll
      like receptor 4.

PMID- 18082198
TI  - Association of polymorphisms in TGFB1 and prostate cancer prognosis.
AB  - PURPOSE: Because of the role of TGFB1 in prostate cancer and progression, we
      hypothesized that polymorphisms of TGFB1 at C-509T may be associated with
      prostate cancer risk and/or more aggressive tumors. MATERIALS AND METHODS: This
      is a case-control study. Controls consisted of male volunteers 40 years old or
      older with a normal digital rectal examination and prostate specific antigen 2.5
      ng/ml or less. Cases consisted of men with biopsy proven prostate cancer. High
      grade prostate cancer included all cancers of Gleason sum 7 or greater. Poor
      prognosis in cases was defined as any stage with Gleason sum 8-10, pT3A (if
      Gleason sum was greater than 7), pT3B or higher (all Gleason sums), any N1 or
      higher, any M1 or higher, or any documented PSA recurrence (biochemical failure).
      Single nucleotide polymorphisms were genotyped using allelic discrimination
      assays. Logistic regression models were used to estimate the OR with the
      corresponding 95% CI for individual racial/ethnic groups. Allelic frequency
      across ethnic/racial groups was compared using Pearson's chi-square test.
      RESULTS: A total of 653 cases and 1,476 controls were genotyped at C-509T. The TT
      genotype showed a significant protective effect against high grade prostate
      cancer (OR 0.482, 95% CI 0.274-0.849). In addition, the TT genotype was
      associated with a decreased risk of poor prognosis prostate cancer (OR 0.488, 95%
      CI 0.236-1.009). Limiting analysis to nonHispanic white men showed that the TT
      genotype had an even more pronounced protective effect for poor prognosis
      prostate cancer (OR 0.297, 95% CI 0.100-0.887). Finally, there was a significant
      difference in the distribution of allelic frequency across racial/ethnic groups
      (p <0.0001). CONCLUSIONS: We observed an association between single nucleotide
      polymorphisms of TGFB1 at C-509T and a decreased risk of aggressive prostate
      cancer. The TT genotype of TGFB1 at C-509T demonstrates a protective effect
      against high grade prostate cancer and cases with poor prognosis.

PMID- 18082199
TI  - Selective prostate cancer thermal ablation with laser activated gold nanoshells.
AB  - PURPOSE: Laser activated gold nanoshell thermal ablation represents a new,
      minimally invasive technology that offers benign tissue sparing thermal ablation
      of malignant tumors. We evaluated the efficacy of this technology for eradicating
      prostate cancer in a subcutaneous tumor model. MATERIALS AND METHODS: The 110 nm
      gold nanoshells with a 10 nm gold shell are designed to act as intense near
      infrared absorbers. PC-3 cells were injected on the dorsum of nude mice in 3
      groups, including 1-gold nanoshell plus near infrared laser, 2-saline alone and 3
      near infrared laser alone. Animals received 7.0 ml/gm body weight (low dose) or
      8.5 ml/gm body weight (high dose) nanoshells via tail vein injection. Control
      animals received saline. A 810 nm near infrared laser with a 200 mu laser fiber
      and an energy setting of 4 W/cm(2) was aimed at the tumor bed for 3 minutes.
      Tumors were measured at days 0, 7, 14 and 21. Tissue temperature was monitored
      during laser activation. Tumors were harvested at day 21 and stained with
      hematoxylin and eosin, and for nicotinamide adenine dinucleotide diaphorase
      activity. RESULTS: We observed 93% tumor necrosis and regression in the high dose
      treated group. Nicotinamide adenine dinucleotide staining corroborated this
      finding. The ablation zone was sharply limited to the laser spot size. There was
      no difference in the size or tumor histology in control groups, indicating a
      benign course for near infrared laser treatment alone. Temperatures up to 65.4C
      were attained in the treated group. CONCLUSIONS: Laser activated gold nanoshell
      ablation is an effective and selective technique for prostate cancer ablation in
      an ectopic murine tumor model.

PMID- 18082200
TI  - Tissue inhibitor of metalloproteinases-3 promoter methylation is an independent
      prognostic factor for bladder cancer.
AB  - PURPOSE: TIMP-3 (tissue inhibitor of metalloproteinases-3) is 1 of 4 members of a
      family of proteins that were originally classified according to their ability to
      inhibit matrix metalloproteinases. We analyzed TIMP-3 methylation in 175 urine
      sediment DNA samples from patients with bladder cancer with well characterized
      clinicopathological parameters, including patient outcome. MATERIALS AND METHODS:
      We examined urine sediment DNA for aberrant methylation of 9 genes, including
      TIMP-3, by quantitative fluorogenic real-time polymerase chain reaction. RESULTS:
      Using an optimal cutoff value by TaqMan(R) quantitation we found that the risk of
      death was statistically significantly higher in patients with higher TIMP-3 and
      ARF methylation (HR 1.99, 95% CI 1.12 to 3.27, p = 0.01 and HR 1.66, 95% CI 1.00
      to 2.76, p = 0.05, respectively) than in patients without/lower TIMP3 and ARF
      methylation in urine. A significant correlation was also seen between the risk of
      death and stage 3 tumor (HR 2.73, 95% CI 1.58 to 4.72, p = 0.003) and metastasis
      (HR 3.32, 95% CI 1.98 to 5.57, p = 0.0001). Multivariate analysis subsequently
      revealed that TIMP-3 methylation was an independent prognostic factor for bladder
      cancer survival with stage and metastasis (p = 0.001 and 0.02, respectively).
      CONCLUSIONS: These results suggest that TIMP-3 promoter methylation could be a
      clinically applicable marker for bladder cancer progression.

PMID- 18082201
TI  - Anti-angiogenic gene therapy for metastatic renal cell carcinoma produces tumor
      growth suppression in an athymic nude mouse model.
AB  - PURPOSE: We investigated the anti-angiogenic and antitumor properties of 2
      adenoviral vectors expressing the endostatin-angiostatin fusion protein Ad
      EndoAngio and the soluble, endothelium specific tyrosine kinase receptor Ad-Tie2
      in a mouse renal cell carcinoma xenograft model. MATERIALS AND METHODS: A total
      of 29 bilateral subcutaneous renal cell carcinomas were induced in athymic nude
      mice. On days 2 and 10 following tumor establishment the mice were intratumorally
      injected with an adenoviral vector in the right flank only. Seven treatment
      groups were randomly assigned, including the control group of 7 mice, the Ad-GFP
      control group of 7, the Ad-Tie2 group of 9, the Ad-EndoAngio group of 8, the Ad
      GFP plus Ad-Tie2 group of 7, the Ad-GFP plus Ad-EndoAngio group of 9 and the Ad
      EndoAngio plus Ad-Tie2 group of 8. Tumor volume was measured biweekly for 60
      days. Additionally, each treatment group was administered fluorescent rhodamine
      conjugated bovine serum albumin dye for vascular imaging. After establishing skin
      windows overlying the tumors dual photon optical imaging was used to
      qualitatively assess the tumor vasculature. RESULTS: Tumors treated with Ad
      EndoAngio, Ad-GFP plus Ad-EndoAngio and Ad-EndoAngio plus Ad-Tie2 demonstrated
      82%, 83% and 87% growth reduction, respectively, compared to controls (p <0.001).
      Furthermore, in vivo imaging revealed a decrease in the number of blood vessels,
      lumen diameter and flow velocity in these treatment groups. CONCLUSIONS:
      Adenoviral vectors expressing endostatin-angiostatin fusion protein have
      effective anti-angiogenic action against human renal cell carcinoma cells as well
      as potential as a novel treatment for metastatic renal cell carcinoma.

PMID- 18082202
TI  - Proteomic identification of interleukin-2 therapy response in metastatic renal
      cell cancer.
AB  - PURPOSE: To detect a predictive protein profile that distinguishes interleukin-2
      therapy responders and nonresponders among patients with metastatic renal cell
      carcinoma we used surface-enhanced laser desorption/ionization time-of-flight
      mass spectrometry. MATERIALS AND METHODS: Protein extracts from 56 patients with
      metastatic clear cell patients renal cell carcinoma obtained from radical
      nephrectomy specimens before interleukin-2 therapy were applied to protein chip
      arrays of different chromatographic properties and analyzed using surface
      enhanced laser desorption/ionization time-of-flight mass spectrometry. A class
      prediction algorithm was applied to identify a subset of protein peaks with
      expression values associated with interleukin-2 response status. Multivariate
      analysis was performed to assess the association between the proteomic profile
      and interleukin-2 response status, controlling for the effect of lymphadenopathy.
      RESULTS: From 513 protein peaks we discovered a predictor set of 11 that
      performed optimally for predicting interleukin-2 response status with 86%
      accuracy (Fisher's p <0.004, permutation p <0.01). Results were validated in an
      independent data set with 72% overall accuracy (p <0.05, permutation p <0.01). On
      multivariate analysis the proteomic profile was significantly associated with the
      interleukin-2 response when corrected for lymph node status (p <0.04).
      CONCLUSIONS: We identified and validated a proteomic pattern that is an
      independent predictor of the interleukin-2 response. The ability to predict the
      probability of the interleukin-2 response could permit targeted selection of the
      patients most likely to respond to interleukin-2, while avoiding unwanted
      toxicity in patients less likely to respond. This proteomic predictor has the
      potential to significantly aid clinicians in the decision making of appropriate
      therapy for patients with metastatic renal cell carcinoma.

PMID- 18082203
TI  - Comparison of renal transplantation outcomes in children with and without bladder
      dysfunction. A customized approach equals the difference.
AB  - PURPOSE: We examined the development of urological abnormalities in a group of
      pediatric renal transplant recipients. MATERIALS AND METHODS: We reviewed 211
      patients younger than 19 years who underwent 226 renal transplants. Three groups
      of patients were studied-136 children with end stage renal disease due to a
      nonurological cause (group 1), 56 children with a urological disorder but with an
      adequate bladder (group 2a) and 19 children with lower urinary tract dysfunction
      and/or inadequate bladder drainage (group 2b). A total of 15 children in group 2b
      underwent bladder augmentation (ureterocystoplasty in 6, enterocystoplasty in 9),
      2 underwent continent urinary diversion, 1 underwent autoaugmentation and 1
      underwent a Mitrofanoff procedure at the bladder for easier drainage. Kidney
      transplantation was performed in the classic manner by extraperitoneal access,
      and whenever possible the ureter was reimplanted using an antireflux procedure.
      RESULTS: At a mean followup of 75 months 13 children had died, 59 grafts were
      lost and 15 children had received a second transplant. Two patients in group 2a
      required a complementary urological procedure to preserve renal function (1
      enterocystoplasty, 1 vesicostomy). A total of 12 major surgical complications
      occurred in 226 kidney transplants (5.3%), with a similar incidence in all
      groups. The overall graft survival at 5 years was 75%, 74% and 84%, respectively,
      in groups 1, 2a and 2b. CONCLUSIONS: With individualized treatment children with
      severely inferior lower urinary tract function may undergo renal transplantation
      with a safe and adequate outcome.

PMID- 18082204
TI  - Biofeedback therapy and home pelvic floor exercises for lower urinary tract
      dysfunction after posterior urethral valve ablation.
AB  - PURPOSE: We sought to determine the effectiveness of biofeedback therapy and home
      pelvic floor exercises in children presenting with lower urinary tract
      dysfunction after posterior urethral valve ablation. MATERIALS AND METHODS:
      Children with urodynamically proved lower urinary tract dysfunction after
      successful valve ablation were enrolled for biofeedback therapy and home pelvic
      floor exercises. Detrusor pressure and electromyography findings were visually
      conveyed to patients on the computer screen. Patients were instructed to
      interrupt detrusor pressure increments by tensing the pelvic floor musculature in
      the presence of detrusor overactivity. In the presence of the nonrelaxing pelvic
      floor patients were first instructed to tighten the pelvic floor musculature and
      then to relax. RESULTS: A total of 30 children were enrolled for biofeedback
      therapy and home pelvic floor exercises between October 2005 and December 2006.
      Median patient age at first session was 5.1 years (range 4.5 to 12). Three
      patients (10%) had an excellent response, and 18 (60%) had a good response, with
      an overall consistent response of 70%. Nine patients (30%) had an inconsistent
      response. Mean number of sessions to achieve consistent urodynamic response was
      3.5 (range 2 to 7). Mean baseline cystometric bladder capacity was 65% of normal
      for age (range 45% to 80%), which improved to a mean of 87.25% (50% to 100%)
      after treatment (p = 0.001). Of the 21 children who had a consistent response 11
      (52%) do not require any further anticholinergics and 15 (71%) are free of clean
      intermittent catheterization. At a mean followup of 11 months (range 5 to 18)
      none of the patients had relapse. CONCLUSIONS: Biofeedback therapy and home
      pelvic floor exercises provide significant and durable relief in post-valve
      ablation persistent lower urinary tract dysfunction.

PMID- 18082205
TI  - What to anticipate with experience in pediatric laparoscopic ablative renal
      surgery.
AB  - PURPOSE: Laparoscopic renal surgery in pediatric urology is moving forward at a
      slower pace than desired. To guide beginning surgeons in what to expect in their
      first years of surgical experience, we present our first 6 years of pediatric
      laparoscopic ablative renal surgery experience to highlight the changing
      laparoscopic surgical parameters during this interval. MATERIALS AND METHODS: We
      retrospectively analyzed all children who underwent laparoscopic ablative renal
      surgery (nephrectomy and heminephroureterectomy) performed by 1 surgeon between
      January 2000 and December 2005. After searching the medical, operative and
      anesthesia records we compared patient characteristics and operative parameters
      such as blood loss and operative time through the years. RESULTS: A total of 39
      children (25 girls, 14 boys) with a mean age of 6.9 years underwent laparoscopic
      renal surgery. Mean operative time was 204 minutes for nephrectomy (26 cases) and
      291 minutes for heminephroureterectomy (14). A statistically significant decrease
      in operative time was noted in the fourth year for nephrectomy cases (20 cases, p
      = 0.003). Blood loss decrease was significant at the fourth year after 10 cases
      of heminephroureterectomy (p = 0.036). Thus, operative time was the only changing
      parameter with experience in nephrectomy, while blood loss changed in
      heminephroureterectomy. CONCLUSIONS: This report details the operative parameters
      changing during the first 6 years as our experience increased in an academic
      setting. This outcome serves as a realistic guide regarding expectations for
      beginning laparoscopists, and should encourage the continuation of pediatric
      laparoscopic renal surgery.

PMID- 18082206
TI  - The efficacy of dihydrotestosterone transdermal gel before primary hypospadias
      surgery: a prospective, controlled, randomized study.
AB  - PURPOSE: We sought to evaluate the efficacy of transdermal dihydrotestosterone
      treatment based on the results of hypospadias repair in children with primary
      hypospadias. MATERIALS AND METHODS: A total of 75 randomized consecutive children
      who were a mean of 33.4 +/- 3.7 months old and had primary hypospadias were
      included in the study between September 2004 and April 2006. While 37 children
      were treated with 2.5% transdermal gel daily, applied directly onto the penile
      shaft and glans for 3 months (group 1), 38 children did not receive any treatment
      preoperatively (group 2). All children underwent hypospadias repair using
      tubularized incised plate urethroplasty. Postoperative complications were
      analyzed using the Mann-Whitney U test with respect to fistulas, urethral
      strictures, diverticula, meatal stenosis, glanular dehiscence and scar formation
      according to the results at 1-year followup. RESULTS: Mean ages of the children
      in groups 1 and 2 were similar (30.8 +/- 5.4 months and 35.1 +/- 5.1 months,
      respectively). The urethral meatus was coronal in 70%, penile in 24% and
      penoscrotal in 5% of the patients in group 1, while it was coronal in 84% and
      penile in 16% of the patients in group 2. Postoperative complications included
      urethrocutaneous fistula in 4 patients (11%) in group 2, compared to 1 patient
      (3%) in group 1 (p >0.05). While 3 patients (8%) in group 2 had glanular
      dehiscence, no patient in the dihydrotestosterone group had this complication (p
      <0.05). There were 2 patients with meatal stenosis in group 2 (5%), and no
      patient with meatal stenosis in group 1 (p >0.05). In addition, there were 16
      patients (42%) with moderate to severe postoperative scar formation in group 2,
      compared to only 2 patients (5%) in the dihydrotestosterone group (p <0.05).
      Finally, there was a significant difference between the overall reoperation rates
      of group 2 (9 patients, 24%) and group 1 (1 patient, 3%, p <0.05). None of our
      patients had signs or symptoms of urethral stricture or urethral diverticulum.
      CONCLUSIONS: Pretreatment with dihydrotestosterone transdermal gel was effective
      in decreasing the complications and improving the cosmetic results after
      hypospadias repair.

PMID- 18082207
TI  - Economic impact of failed or delayed primary repair of bladder exstrophy:
      differences in cost of hospitalization.
AB  - PURPOSE: Patients with bladder exstrophy and failed primary newborn closure or
      who undergo delayed primary repair have suboptimal functional outcomes. We sought
      to determine whether these patients also have costlier, more resource intensive
      hospitalizations compared to patients who undergo neonatal primary closure.
      MATERIALS AND METHODS: We reviewed hospital coding records to identify patients
      who underwent surgical repair of classic bladder exstrophy at The Johns Hopkins
      Hospital between 1997 and 2006, and obtained charge records for each
      hospitalization. Total hospital charges (excluding professional fees) were
      inflation adjusted to year 2005 dollars. Cases were identified as newborn primary
      repair, delayed primary repair or reclosure of failed prior repair. RESULTS:
      Results of classic exstrophy repair were analyzed in 80 patients. A total of 34
      procedures were newborn primary repairs, 15 were delayed primary repairs and 31
      were reclosures of failed prior repair. All of the patients undergoing delayed
      primary repairs and reclosures underwent osteotomy, compared to only 21% of those
      undergoing newborn primary repair. Overall mean inflation adjusted
      hospitalization charge was $66,348 +/- $26,625 (range $29,689 to $179,403).
      Newborn closures were significantly less costly (mean charge $53,188 +/- $15,086)
      than either reclosure ($71,621 +/- $19,366) or delayed primary closure ($85,278
      +/- $42,354, p <0.0001). Controlling for multiple variables in a regression model
      showed that the primary factors associated with charges were operative time, days
      in intensive care unit and length of stay. Length of stay and operative times
      were significantly shorter in the newborn surgical group, likely accounting for
      the lower costs in this group (despite higher intensive care unit use). Mean
      hospital charges and mean length of stay increased during the study period.
      CONCLUSIONS: Primary newborn exstrophy repair is associated with lower surgical
      hospitalization costs compared to delayed primary repair and reclosure. Combined
      with previous data on clinical outcomes, these data reiterate the paramount
      importance of achieving a successful initial newborn closure whenever possible.

PMID- 18082208
TI  - Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in
      children with low grade vesicoureteral reflux: results from a prospective
      randomized study.
AB  - PURPOSE: Antibiotic prophylaxis is given to children at risk for urinary tract
      infection. However, evidence concerning its effectiveness in grade I to III
      vesicoureteral reflux is lacking. The objective of this study was to determine
      whether antibiotic prophylaxis reduces the incidence of urinary tract infection
      in young children with low grade vesicoureteral reflux. MATERIALS AND METHODS:
      Children 1 month to 3 years old with grade I to III vesicoureteral reflux were
      assigned randomly to receive daily cotrimoxazole or no treatment, and followed
      for 18 months. A urinary tract infection constituted an exit criterion. Infection
      free survival rates were calculated using the Kaplan-Meier method and compared
      using the log rank test. RESULTS: A total of 225 children were enrolled in the
      study. Distribution of gender, age at inclusion and reflux grade were similar
      between the 2 groups. There was no significant difference in the occurrence of
      urinary tract infection between the 2 groups (17% vs 26%, p = 0.2). However, a
      significant association was found between treatment and patient gender (p =
      0.017). Prophylaxis significantly reduced urinary tract infection in boys (p =
      0.013), most notably in boys with grade III vesicoureteral reflux (p = 0.042).
      CONCLUSIONS: These data suggest that antibiotic prophylaxis does not reduce the
      overall incidence of urinary tract infection in children with low grade
      vesicoureteral reflux. However, such a strategy may prevent further urinary tract
      infection in boys with grade III reflux.

PMID- 18082209
TI  - Study characteristics of abstracts presented at the annual meetings of the
      southeastern section of the American Urological Association (1996-2005).
AB  - PURPOSE: We determined study characteristics, authorship and institutional origin
      of studies presented in abstract form at the Southeastern Section of the American
      Urological Association annual meetings and identified predictors of full text
      publication. MATERIALS AND METHODS: All abstracts of poster and podium
      presentations from the Southeastern Section of the American Urological
      Association annual meetings from 1996 to 2005 were reviewed. A standardized
      evaluation form was developed and tested in 2 subsets of 50 abstracts, and then
      applied by 2 individual reviewers with specific coding instructions. Predictor
      variables analyzed included study origin, design, topic, domain, presentation
      form, number of patients, reporting of statistical analysis and gender.
      Univariate and multivariate analysis was applied using SPSS version 14.0.
      RESULTS: A total of 1,195 abstracts were found eligible for review. The mean
      number of abstracts presented per year was 120 +/- 16 (range 107 to 146). In
      clinical studies (1,068) approximately three-quarters of the abstracts reported
      case series (801, 75.0%). Cohort studies accounted for 11.2% of the abstracts and
      4.0% were randomized controlled trials or systematic reviews/meta-analyses.
      Median followup was 64 months (range 17 to 126) and the overall publication rate
      was 33.5%. First and senior female authorship were identified in 6.2% (74) and
      5.4% (64) of abstracts presented, respectively. CONCLUSIONS: A majority of
      studies presented at the Southeastern Section of the American Urological
      Association annual meetings continue to represent small case series that may not
      be well suited to guide clinical decision making. Only a third of studies are
      subsequently published in the peer reviewed literature. The percentage of
      abstracts with female authorship remains low suggesting that increased efforts to
      involve women in urological research are indicated.

PMID- 18082210
TI  - The EZ Trainer: validation of a portable and inexpensive simulator for training
      basic laparoscopic skills.
AB  - PURPOSE: We assessed the face and content validity of a new portable laparoscopic
      trainer, the EZ Trainer. MATERIALS AND METHODS: The portable, affordable EZ
      trainer system was conceived, designed and commissioned by academic surgeons from
      the departments of urology at our 2 institutions with the express purpose of
      advancing laparoscopic surgical training. A total of 42 participants, including
      general surgeons, obstetricians/gynecologists, urologists and industry
      representatives, assessed the face and the content validity of the trainer using
      a standard questionnaire. Participants were stratified into high (greater than 30
      laparoscopic cases per year) and low (less than 30 cases per year) volume
      laparoscopists. RESULTS: Of the participants 96% rated the trainer as a realistic
      laparoscopic training format. Of high volume laparoscopists 81.5% rated the
      trainer as comfortable to use, 92.6% found that the trainer was a realistic
      practice format, 70.4% would purchase the trainer for personal use and 85.2%
      would recommend that the trainer be made available to surgical residents in their
      discipline. Of low volume laparoscopists 87% rated the trainer as comfortable to
      use, 93.3% found that the trainer was a realistic practice format, 73.3% would
      purchase the trainer for personal use and 80% would recommend that the trainer be
      made available to diverse surgical residents. CONCLUSIONS: The EZ trainer system
      has face and content validity as a portable laparoscopic trainer across a broad
      range of surgical disciplines.

PMID- 18082211
TI  - Urinary incontinence prevalence: results from the National Health and Nutrition
      Examination Survey.
AB  - PURPOSE: We determined racial differences in urinary incontinence prevalence
      using the 2001-2004 National Health and Nutrition Examination Survey. MATERIALS
      AND METHODS: The National Health and Nutrition Examination Survey is a continuous
      survey of a representative sample of the noninstitutionalized United States
      population. Demographic, self-reported racial/ethnic data and responses to the
      urinary portion of the survey were available for 4,229 women older than 20 years.
      We classified women by urinary incontinence subtype, that is pure stress
      incontinence, pure urge incontinence or mixed incontinence. Logistic regression
      models were fitted to investigate racial differences by type of urinary
      incontinence. RESULTS: The sample was racially and ethnically diverse with 58%
      white nonHispanic, 22% Mexican-American and 20% black nonHispanic. Women were
      divided into 3 age ranges of 20 to 39 years old (36.3%), 40 to 59 (28%), and 60
      years old or older (35.7%). Of the 4,229 women in the analytical sample 49.6%
      (2,098) reported urinary incontinence symptoms. Of those reporting incontinence
      symptoms 49.8% reported pure stress incontinence, 34.3% mixed incontinence and
      15.9% pure urge incontinence. The odds of pure stress incontinence in white and
      Mexican-American women were approximately 2.5 times higher than in black women
      (OR 2.79, CI 2.1-3.8 and OR 2.5, CI 1.9-3.4) after adjusting for age, parity,
      body mass index and activity level. In contrast, black and Mexican-American women
      were more likely to report pure urge incontinence compared to white women (OR
      0.6, CI 0.43-0.8). The prevalence of mixed incontinence was not significantly
      different among race/ethnicity groups. CONCLUSIONS: Race/ethnicity differences
      exist in self-reported urinary incontinence. While self-reported urinary
      incontinence is prevalent in United States community dwelling women regardless of
      racial background, the odds of pure stress incontinence are at least 2.5-fold
      higher in white and Mexican-American women than in black women.

PMID- 18082212
TI  - Effects of urinary incontinence, comorbidity and race on quality of life outcomes
      in women.
AB  - PURPOSE: We investigated the effects of comorbidity and urinary incontinence on
      both generic and incontinence specific quality of life outcome measures, and
      investigated whether the association between urinary incontinence and quality of
      life varies by race. MATERIALS AND METHODS: Study participants were 2,109 women
      40 to 69 years old randomly selected from an urban health maintenance
      organization and interviewed in person for a study of risk factors for urinary
      incontinence. The sample was racially diverse consisting of 48% white, 18% black,
      17% Hispanic and 16% Asian-American women. In addition to incontinence,
      reproductive and medical history questionnaires, all participants completed the
      Medical Outcomes Study Short Form 36, a measure of health related quality of
      life. All participants with daily and weekly incontinence (29%) completed the
      Incontinence Impact Questionnaire, an incontinence specific quality of life
      measure. The health maintenance organization's inpatient and outpatient
      electronic databases were used to calculate a Charlson comorbidity index score
      for each participant. ANCOVA was used to produce a model adjusting for
      sociodemographic variables, comorbidity and incontinence frequency. The same
      model was run for each of 4 racial groupings to examine differences by
      race/ethnicity. RESULTS: Urinary incontinence is significantly associated with a
      decreased quality of life and those with more frequent incontinence have
      significantly lower quality of life scores. In our model the Charlson score, an
      objective measure of comorbidity based on hospital and physician records, also
      has a significant negative impact on quality of life. When comorbidity is
      controlled, incontinence frequency continues to have a significant negative
      association with quality of life except among the sickest women. For women with
      the greatest extent of comorbidity, incontinence frequency is not significantly
      associated with negative quality of life outcomes. We did not find clear patterns
      of variation by race. CONCLUSIONS: Urinary incontinence and comorbidity each have
      an independent and significant role in reducing quality of life outcomes for all
      but the sickest women.

PMID- 18082213
TI  - Attenuation of oxidative stress after varicocelectomy in subfertile patients with
      varicocele.
AB  - PURPOSE: We examined changes due to oxidative damage to spermatozoa and
      alterations in antioxidant capacity in subfertile patients with varicocele before
      and after varicocelectomy in a prospective study. MATERIALS AND METHODS: A total
      of 30 young subfertile male patients with varicocele were recruited in this
      study. Varicocele was diagnosed by physical examination and Doppler ultrasound.
      Semen analysis was performed in the 30 patients before and 6 months after
      varicocelectomy using a computer assisted semen analyzer. The parameters for
      evaluating oxidative stress changes were 4977 bp deletion of mitochondrial DNA in
      sperm, as detected by polymerase chain reaction, the 8-OHdG (8-hydroxy-2'
      deoxyguanosine) content in spermatozoa DNA, as measured by a high performance
      liquid chromatography electrochemical method, and seminal plasma protein thiols
      and ascorbic acid, as measured by spectrophotometric methods. RESULTS: Semen
      quality, including motility, morphology and sperm density, was improved in 22
      patients (73.3%) after varicocelectomy. The incidence of 4977 bp deletion of
      mitochondrial DNA in sperm was 40% (12 of 30 patients) and 13.3% (4 of 30) before
      and after surgery, respectively. Mean +/- SD 8-OHdG content in sperm DNA, and
      seminal plasma protein thiols and ascorbic acid were 10.27 +/- 2.24/10(5) 2'
      deoxyguanosine, 0.77 +/- 0.75 nmole/ml and 1.87 +/- 0.40 mg/dl before operation,
      and 5.95 +/- 1.46/10(5) 2'-deoxyguanosine, 3.00 +/- 1.17 nmole/ml and 3.12 +/-
      0.94 mg/dl after surgery, respectively. The incidence of 4977 bp deletion of
      mitochondrial DNA in sperm and the level of 8-OHdG in sperm DNA were decreased,
      and seminal plasma protein thiols and ascorbic acid were increased significantly
      in all 30 patients after varicocelectomy. Also, in the 8 patients in whom semen
      quality did not improve after surgery a significant decrease in 8-OHdG in sperm
      DNA, and a significant increase in seminal plasma protein thiols and ascorbic
      acid were observed. CONCLUSIONS: Subfertile patients with varicocele had a
      significant decrease in oxidative damage in sperm DNA and an increase in
      antioxidant capacity in seminal plasma after varicocelectomy, indicating that
      surgery is effective treatment in such patients.

PMID- 18082214
TI  - Sexual function and genital sensitivity following feminizing genitoplasty for
      congenital adrenal hyperplasia.
AB  - PURPOSE: Female sex assignment followed by cosmetic genitoplasty to feminize the
      genitalia in infancy remains standard practice in the clinical management of
      ambiguous genitalia. The effects of surgery on genital sensitivity have never
      been objectively evaluated. To our knowledge the current study is the first to
      evaluate genital sensitivity and sexual function in women with congenital adrenal
      hyperplasia. MATERIALS AND METHODS: A total of 28 women with congenital adrenal
      hyperplasia and 10 normal controls were recruited. Details of prior genital
      surgery were obtained from medical records. Sensitivity thresholds for the
      clitoris and upper vagina were measured using a GenitoSensory Analyzer (Medoc,
      Ramat, Israel). Sexual function was assessed using a standardized measure.
      RESULTS: Of 28 women with congenital adrenal hyperplasia 24 had undergone
      feminizing genital surgery. In women who underwent surgery there was significant
      impairment to sensitivity in the clitoris compared to controls. No difference was
      observed for the sensitivity threshold in the upper vagina, where surgery had not
      been done in any of the women. Data on the 4 women with congenital adrenal
      hyperplasia who had not undergone surgery were similar to those in controls.
      Sexual function difficulties were more severe in women who underwent surgery,
      especially vaginal penetration difficulties and intercourse frequency. Linear
      relationships were observed for impairment to sensitivity and severity of sexual
      difficulties. CONCLUSIONS: Genital sensitivity is impaired in areas where
      feminizing genital surgery had been done and impairment to sensitivity are
      linearly related to difficulties in sexual function. The new information may help
      inform clinicians and parents making difficult decisions about genital surgery
      for infants with ambiguous genitalia.

PMID- 18082215
TI  - Halving ischemia time during laparoscopic partial nephrectomy.
AB  - PURPOSE: Laparoscopic partial nephrectomy has demonstrated renal functional and 5
      year oncological outcomes equivalent to those of open partial nephrectomy. A
      remaining critique of laparoscopic partial nephrectomy is its 10-minute longer
      ischemia time compared to open surgery. We present an early unclamping
      laparoscopic partial nephrectomy technique that decreases ischemia time by more
      than 50%. MATERIALS AND METHODS: During standard laparoscopic partial nephrectomy
      renal reconstruction is completely performed under ischemic conditions. In our
      early unclamping technique only the initial parenchymal suturing is performed
      under ischemia with the remainder of bolstered renorrhaphy performed in the
      revascularized kidney. Of 100 consecutive nonrandomized patients the initial 50
      underwent standard laparoscopic partial nephrectomy (group 1) and the subsequent
      50 underwent early unclamping laparoscopic partial nephrectomy (group 2).
      RESULTS: Baseline demographics (body mass index, mean tumor size and
      central/hilar tumor location) and intraoperative parameters (need for
      pelvicaliceal repair, blood loss and operative time) were similar in the groups.
      However, warm ischemia time was significantly lower in group 2 (31.1 vs 13.9
      minutes, p <0.0001). In groups 1 and 2 ischemia time was 30 minutes or greater in
      60% vs 0% of patients (p <0.0001). Compared to group 1 overall complications (22%
      vs 16%), postoperative renal hemorrhage (4% vs 2%) and the re-intervention rate
      (16% vs 6%) trended lower in group 2 (p = not significant). No patient had a
      positive cancer margin, required open conversion or showed renal dysfunction.
      CONCLUSIONS: This early unclamping laparoscopic partial nephrectomy technique
      significantly decreases ischemia time by more than 50% and also trends toward
      decreased complications. Our current mean ischemia time of less than 14 minutes
      is lower than or equivalent to that in contemporary open partial nephrectomy
      series.

PMID- 18082216
TI  - The effects of dutasteride, tamsulosin and combination therapy on lower urinary
      tract symptoms in men with benign prostatic hyperplasia and prostatic
      enlargement: 2-year results from the CombAT study.
AB  - PURPOSE: We investigated whether combination therapy with dutasteride and
      tamsulosin is more effective than either monotherapy alone for improving symptoms
      and long-term outcomes in men with moderate to severe lower urinary tract
      symptoms and prostatic enlargement (30 cc or greater). We report preplanned 2
      year analyses. MATERIALS AND METHODS: The CombAT study is an ongoing,
      multicenter, randomized, double-blind, parallel group study. Men 50 years or
      older with a clinical diagnosis of benign prostatic hyperplasia, International
      Prostate Symptom Score 12 points or greater, prostate volume 30 cc or greater,
      total serum prostate specific antigen 1.5 ng/ml or greater to 10 ng/ml or less
      and peak urinary flow greater than 5 to 15 ml per second or less with a minimum
      voided volume of 125 ml or greater were randomized to 0.5 mg dutasteride, 0.4 mg
      tamsulosin or the combination once daily for 4 years. Symptoms were assessed
      every 3 months and peak urinary flow was assessed every 6 months. The primary end
      point at 2 years was the change in International Prostate Symptom Score from
      baseline. RESULTS: Combination therapy resulted in significantly greater
      improvements in symptoms vs dutasteride from month 3 and tamsulosin from month 9,
      and in benign prostatic hyperplasia related health status from months 3 and 12,
      respectively. There was a significantly greater improvement from baseline in peak
      urinary flow for combination therapy vs dutasteride and tamsulosin monotherapies
      from month 6. There was a significant increase in drug related adverse events
      with combination therapy vs monotherapies, although most did not result in the
      cessation of therapy. CONCLUSIONS: In men with moderate to severe lower urinary
      tract symptoms and prostate enlargement (30 cc or greater) combination therapy
      provides a significantly greater degree of benefit than tamsulosin or dutasteride
      monotherapy.

PMID- 18082218
TI  - A new device for the treatment of post-prostatectomy incontinence: adjustable
      perineal male sling.
AB  - PURPOSE: We describe a novel male sling device for the treatment of post
      prostatectomy incontinence that allows tension adjustment over the urethra
      postoperatively. We report the short-term results in patients with severe
      incontinence who were treated with this device. MATERIALS AND METHODS: An
      adjustable male sling procedure was performed in 19 patients with a mean age of
      67.5 years (range 59 to 80) who had severe post-prostatectomy incontinence. A
      tissue expander, including a silicone balloon expander, a small tube and a self
      sealing valve that allowed the expander to gradually fill with saline solution,
      was used for this procedure. A pocket was created to anchor the balloon expander
      in its position by suturing 2 polypropylene meshes to each other around the
      filled balloon expander. The empty silicone balloon expander was inserted into
      this pocket and the sling was placed over the urethra. The injection port was
      secured inside the scrotum and connected to the balloon expander. RESULTS:
      Average operative time was 63 minutes (range 45 to 90). A total of 11 patients
      required injections. The average number of adjustments was 2 (range 1 to 3) and
      average injected volume was 6.3 cc (range 5 to 10). Of the patients 15 (78.9%)
      were completely dry and 2 (10.5%) improved significantly to 1 to 2 pads per day
      at a mean followup of 17.3 months (range 12 to 25). CONCLUSIONS: Our short-term
      results suggest that a tissue expander makes the male sling procedure more
      effective. However, since it is a new device, long-term results are needed to
      evaluate durability.

PMID- 18082217
TI  - Effect of saw palmetto soft gel capsule on lower urinary tract symptoms
      associated with benign prostatic hyperplasia: a randomized trial in Shanghai,
      China.
AB  - PURPOSE: We determined the effect of Prostataplex in men with lower urinary tract
      symptoms associated with benign prostatic hyperplasia. MATERIALS AND METHODS: A
      total of 92 Chinese men between 49 and 75 years old with lower urinary tract
      symptoms were randomly assigned in this double-blind, placebo controlled trial.
      The 46 patients in the intervention group were given 2 Prostataplex soft gels
      daily for 12 weeks, while the 46 in the control group were given 2 placebo soft
      gels for the same time. RESULTS: The treated and control groups appeared to have
      more than a 95% compliance rate, as judged by counting the remaining pills in the
      bottle collected at the end of trial months 1 to 3. After 12 weeks of
      intervention the mean +/- SD maximum urinary flow rate was significantly higher
      in the treatment group than in the control group (14.07 +/- 2.56 vs 11.74 +/-
      1.23 ml per second, p <0.001), while relative urinary resistance was
      significantly lower in the treatment group than in the control group (2.35 +/-
      0.83 vs 3.02 +/- 1.18, p = 0.002). While there was no significant difference in
      mean prostate volume or International Prostate Symptom Score between the 2
      groups, 18 of 46 patients (39.1%) in the treatment group showed an International
      Prostate Symptom Score improvement (decrease of 3 or greater) after intervention,
      whereas only 1 of 46 (2.2%) in the control group showed an International Prostate
      Symptom Score improvement (chi-square test p <0.001). CONCLUSIONS: Prostataplex
      may have short-term effects in improving symptoms and objective measures in
      Chinese men with lower urinary tract symptoms associated with benign prostatic
      hyperplasia.

PMID- 18082219
TI  - Predictors of success with postoperative voiding trials after a mid urethral
      sling procedure.
AB  - PURPOSE: We identified predictors of passing a voiding trial after incontinence
      surgery with a mid urethral sling and examined if successful performance on a
      voiding trial was maintained. MATERIALS AND METHODS: A total of 89 women
      scheduled for incontinence surgery were enrolled from July 2005 until April 2006.
      Voiding trials were performed the day of discharge from the hospital, with a two
      thirds volume void after a 300 ml fill considered passing. Those who passed
      underwent a second voiding trial 3 hours later. RESULTS: Of the participants 60
      (67.4%) underwent tension-free vaginal tape surgery, 29 underwent transobturator
      tape (32.6%) and 64 (71.9%) underwent concurrent vaginal repairs. A total of 59
      (67.0%) participants passed the first voiding trial. Univariate analysis
      identified 12 potential predicting variables for passing the first voiding trial.
      From these 12, model building via backward stepwise logistic regression found
      maximum flow on preoperative uroflowmetry to be the only significant predictive
      variable (p = 0.0002). Of the 59 women who passed the initial voiding trial 9
      (16.4%) failed the second voiding trial. None of the 11 participants who had
      maximal flow rates greater than 30 cc per second failed the first or second
      voiding trial, whereas 17 of 22 subjects (77.3%) who had maximal flow rates less
      than 15 cc per second failed either of these trials. CONCLUSIONS: Maximum flow
      rates on preoperative uroflowmetry were the best predictor of passing an initial
      voiding trial after undergoing a mid urethral sling procedure for incontinence.
      However, the ability to maintain performance on a second voiding trial, even only
      3 hours after passing an initial trial, is not assured.

PMID- 18082220
TI  - Minimum 24-month followup of the sling for the treatment of stress urinary
      incontinence.
AB  - PURPOSE: The SPARC procedure is a retropubic approach for the placement of a
      synthetic polypropylene sling for stress urinary incontinence. Although the
      approach appears to be efficacious, there still exist limited long-term data. We
      report our experience with SPARC at a minimum followup of 24 months. MATERIALS
      AND METHODS: Patients with stress urinary incontinence undergoing a SPARC sling
      procedure were entered into a prospective, institutional review board approved
      database. Postoperatively patients were asked to complete quality of life
      questionnaires at 6 months and annually thereafter. Success was defined by
      questionnaire response of 1 or fewer stress urinary incontinence episode per week
      or greater than 70% subjective improvement in those with greater than 1 stress
      urinary incontinence episodes per week. RESULTS: A total of 307 patients were
      identified during a 5-year period, of whom 280 were more than 24 months from
      surgery. Of the patients 154 (55%) had questionnaire followup at 24 months or
      greater from surgery (mean 36, median 36, range 24 to 49). Mean Valsalva leak
      point pressure in this subset of patients was 66 cm H(2)O (median 63, range 15 to
      175). Of the patients 106 (68.8%) reported 1 or greater stress urinary
      incontinence episodes per week and 11 (7.1%) reported greater than 70% subjective
      improvement despite greater than 1 stress urinary incontinence episodes per week.
      Based on these definitions 75.9% of the cases were considered successful.
      CONCLUSIONS: The antegrade polypropylene mid urethral sling appears effective and
      most patients are satisfied with the outcome. The ease and minimally invasive
      nature of this technique does not preclude significant complications.
      Nevertheless, results in this series are competitive with those of other
      available surgical options.

PMID- 18082221
TI  - Treatment of obturator neuralgia with laparoscopic neurolysis.
AB  - PURPOSE: Obturator neuralgia is a cause of pelvic and perineal pain that is
      rarely suggested, probably because it is poorly understood. We report the results
      of a pilot study of laparoscopic treatment for obturator neuralgia. MATERIALS AND
      METHODS: Seven patients (8 nerves) with obturator neuralgia were treated at our
      department. The etiology was idiopathic in 3 cases and iatrogenic following
      inguinal hernia surgery in 3 and TVT(R) repair in 2. The diagnosis was based on
      allodynic pain of the anterior and internal surface of the thigh, which was
      associated with limping with a sidestepping gait. It was confirmed by an
      anesthetic block under computerized tomography monitoring using a posterior
      approach. RESULTS: Treatment consisted of transperitoneal laparoscopic neurolysis
      with dissection of the nerve and section of the scarring fibrosis or prosthetic
      mesh in contact with it. In idiopathic cases nerve release was performed by
      sectioning the internal obturator muscle and the obturator membrane, causing
      compression and making it possible to widen the obturator foramen. At a mean
      followup of 16 months the rate of an at least 50% improvement in pain was 87.5%
      (7 of 8 cases), including complete disappearance of pain in 50% (4 of 8).
      CONCLUSIONS: Minimally invasive treatment with laparoscopic truncular release of
      obturator neuralgia yielded encouraging and good results.

PMID- 18082222
TI  - Seasonal variations in urinary calculi attacks and their association with
      climate: a population based study.
AB  - PURPOSE: In this nationwide population based study we used 5-year data on urinary
      calculi patient visits to emergency departments in Taiwan to investigate the
      seasonal variation in urinary calculi attacks and the association with 5 climatic
      parameters. MATERIALS AND METHODS: Comprehensive details on total admissions to
      emergency departments were obtained from the Taiwan National Health Insurance
      Research Database (1999 to 2003), providing monthly urinary calculi attack rates
      per 100,000 of the population. Subgroups of urinary calculi incidences were
      created based on gender and 3 age groups (18 to 44, 45 to 64 and 65 years old or
      older). Following adjustment for time trend effects, evaluation of the monthly
      urinary calculi attack rates and the effects of climatic factors was performed
      using auto-regressive integrated moving average regression methodology. RESULTS:
      The seasonal trends in the monthly urinary calculi attack rates revealed a peak
      in July to September, followed by a sharp decline in October, with the auto
      regressive integrated moving average tests for seasonality demonstrating
      significance for each gender group, for each age group and for the whole sample
      (all p <0.001). Although significant associations were found between ambient
      temperature, atmospheric pressure and hours of sunshine vis-a-vis monthly urinary
      calculi attack rates for the total population, after adjustment for trends and
      seasonality, ambient temperature was found to be the sole major factor having any
      positive association with the monthly attack rates. CONCLUSIONS: We conclude that
      seasonal variations do exist in the monthly urinary calculi attack rates for all
      age and gender populations, and that following time series statistical
      adjustment, only ambient temperature had any consistent association with monthly
      attack rates.

PMID- 18082223
TI  - Muscle tenderness in men with chronic prostatitis/chronic pelvic pain syndrome:
      the chronic prostatitis cohort study.
AB  - PURPOSE: Myofascial pain is a possible etiology for category III chronic
      prostatitis/chronic pelvic pain syndrome, either secondary to
      infection/inflammation or as the primary cause. We documented tenderness on
      physical examination in a large multicenter cohort of patients with chronic
      pelvic pain syndrome and compared to controls. MATERIALS AND METHODS: Data were
      reviewed from the National Institutes of Health Chronic Prostatitis Cohort study
      on 384 men with chronic pelvic pain syndrome and 121 asymptomatic controls who
      had complete unblinded physical examination data from 7 clinical centers between
      October 1998 and August 2001. Tenderness in 11 sites including prostate,
      genitals, abdomen and pelvic floor together with prostate size and consistency
      was evaluated. Data were correlated with cultures and symptoms. RESULTS: Overall
      51% of patients with chronic pelvic pain syndrome and 7% of controls had any
      tenderness. The most common site was prostate (41% chronic pelvic pain syndrome,
      5% controls), followed by external and internal pelvic floor (13% and 14% chronic
      pelvic pain syndrome, 0 controls) and suprapubic area (9% chronic pelvic pain
      syndrome, 0 controls). Of patients with chronic pelvic pain syndrome 25% had 1
      tender site, 11% had 2 and 6% had 3 tender sites. Tenderness did not correlate
      with inflammation or infection in the prostate fluid. Prostate consistency was
      normal in 79% of patients with chronic pelvic pain syndrome and in 95% of
      controls, and did not correlate with symptom severity. Patients with chronic
      pelvic pain syndrome with any tenderness had significantly higher Chronic
      Prostatitis Symptom Index scores at baseline and at 1 year (24.1 vs 21.2 and 20.2
      vs 17.5, p <0.0001) compared to patients without tenderness. CONCLUSIONS:
      Abdominal/pelvic tenderness is present in half of the patients with chronic
      pelvic pain syndrome but only 7% of controls. Extraprostatic tenderness may
      identify a cohort of patients with a neuromuscular source of pain.

PMID- 18082224
TI  - Followup of patients with interstitial cystitis responsive to treatment with
      intravesical bacillus Calmette-Guerin or placebo.
AB  - PURPOSE: We evaluated the longer term response in patients with interstitial
      cystitis who initially responded to intravesical bacillus Calmette-Guerin or
      placebo in a randomized clinical trial. MATERIALS AND METHODS: Patients with
      interstitial cystitis who responded positively to treatment with bacillus
      Calmette-Guerin or placebo after 34 weeks of followup in a double-blind clinical
      trial were followed for an additional 34 weeks in an observational study to
      assess response durability. Outcomes at 68 weeks included a patient reported
      global response assessment, 24-hour voiding diary, and pain, urgency and
      validated interstitial cystitis symptom indexes. RESULTS: Of responders to
      bacillus Calmette-Guerin or placebo in the clinical trial 38 continued extended
      followup in the observational study. A total of 12 (75%) responders who received
      placebo and 19 (86%) who received bacillus Calmette-Guerin considered themselves
      to remain moderately or markedly improved at week 68. Improved symptom outcomes
      were also generally maintained during followup in the 2 groups. CONCLUSIONS: Most
      patients who respond to therapy with intravesical bacillus Calmette-Guerin or
      placebo maintain improved symptoms for up to 68 weeks after the initiation of
      therapy. However, initial response rates are low and placebo responders
      demonstrated essentially the same durability of response as bacillus Calmette
      Guerin responders. These results argue against the routine use of bacillus
      Calmette-Guerin in this patient group.

PMID- 18082225
TI  - Modelling the formation of necrotic regions in avascular tumours.
AB  - The mechanisms underlying the formation of necrotic regions within avascular
      tumours are not well understood. In this paper, we examine the relative roles of
      nutrient deprivation and of cell death, from both the proliferating phase of the
      cell cycle via apoptosis and from the quiescent phase via necrosis, in changing
      the structure within multicellular tumour spheroids and particularly the
      accumulation of dead cell material in the centre. A mathematical model is
      presented and studied that accounts for nutrient diffusion, changes in cell
      cycling rates, the two different routes to cell death as well as active motion of
      cells and passive motion of the dead cell material. In studying the accumulation
      of dead cell matter we do not distinguish between the route by which each was
      formed. The resulting mathematical model is examined for a number of scenarios.
      Results show that in many cases the size of the necrotic core is closely
      correlated with low levels in nutrient concentration. However, in certain cases,
      particularly where the rate of necrosis is large, the resulting necrotic core can
      lead to regions of non-negligible nutrient concentration-dependent upon the mode
      of cell death.

PMID- 18082226
TI  - Temporally distinct response of irradiated normal human fibroblasts and their
      bystander cells to energetic heavy ions.
AB  - Ionizing radiation-induced bystander effects have been documented for a multitude
      of endpoints such as mutations, chromosome aberrations and cell death, which
      arise in nonirradiated bystander cells having received signals from directly
      irradiated cells; however, energetic heavy ion-induced bystander response is
      incompletely characterized. To address this, we employed precise microbeams of
      carbon and neon ions for targeting only a very small fraction of cells in
      confluent fibroblast cultures. Conventional broadfield irradiation was conducted
      in parallel to see the effects in irradiated cells. Exposure of 0.00026% of cells
      led to nearly 10% reductions in the clonogenic survival and twofold rises in the
      apoptotic incidence regardless of ion species. Whilst apoptotic frequency
      increased with time up to 72 h postirradiation in irradiated cells, its frequency
      escalated up to 24h postirradiation but declined at 48 h postirradiation in
      bystander cells, indicating that bystander cells exhibit transient commitment to
      apoptosis. Carbon- and neon-ion microbeam irradiation similarly caused almost
      twofold increments in the levels of serine 15-phosphorylated p53 proteins,
      irrespective of whether 0.00026, 0.0013 or 0.0066% of cells were targeted.
      Whereas the levels of phosphorylated p53 were elevated and remained unchanged at
      2h and 6h postirradiation in irradiated cells, its levels rose at 6h
      postirradiation but not at 2h postirradiation in bystander cells, suggesting that
      bystander cells manifest delayed p53 phosphorylation. Collectively, our results
      indicate that heavy ions inactivate clonogenic potential of bystander cells, and
      that the time course of the response to heavy ions differs between irradiated and
      bystander cells. These induced bystander responses could be a defensive mechanism
      that minimizes further expansion of aberrant cells.

PMID- 18082227
TI  - Interaction of cytochrome P4501A1 genotypes with other risk factors and
      susceptibility to lung cancer.
AB  - Lung cancer is the most common cause of death throughout the world with cigarette
      smoking being established as the major etiological factor in lung cancer. Since
      not much information is available regarding the polymorphism in drug metabolizing
      enzymes and lung cancer risk in the Indian population, the present case-control
      study attempted to investigate the association of polymorphisms in cytochrome
      P450 1A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1) with risk to squamous
      cell carcinoma of lung malignancy. Patients suffering from lung cancer (n=200)
      and visiting OPD facility of Department of Radiotherapy, King George's Medical
      University, Lucknow, were included in the study. Equal number (n=200) of age and
      sex matched healthy individuals were also enrolled in the study. Our data
      revealed that the variant genotypes of CYP1A1*2A, CYP1A1*2C and CYP1A1*4 were
      found to be over represented in the lung cancer patients when compared to
      controls. CYP1A1*2A variant genotypes (combined heterozygous and mutant
      genotypes) revealed significant association towards the lung cancer risk (OR:
      1.93, 95%CI: 1.28-2.89, p=0.002). Likewise, GSTM1 null genotypes were found to be
      over represented in patients when compared to controls. Haplotype analysis
      revealed that CYP1A1 haplotype, C-G-C increased the lung cancer risk (OR: 3.90,
      95%CI: 1.00-15.04, p=0.025) in the patients. The lung cancer risk was increased
      several two-to fourfold in the patients carrying the genotype combinations of
      CYP1A1*2A and GSTM1 suggesting the role of gene-gene interaction in lung cancer.
      Cigarette smoking or tobacco chewing or alcohol consumption was also found to
      interact with CYP1A1 genotypes in increasing the risk to lung cancer further
      demonstrating the role of gene-environment interaction in development of lung
      cancer.

PMID- 18082228
TI  - Central blockade of melanocortin receptors attenuates the metabolic and locomotor
      responses to peripheral interleukin-1beta administration.
AB  - Loss of appetite and cachexia is an obstacle in the treatment of chronic
      infection and cancer. Proinflammatory cytokines released from activated immune
      cells and acting in the central nervous system (CNS) are prime candidates for
      mediating these metabolic changes, potentially affecting both energy intake as
      well as energy expenditure. The effect of intravenous administration of two
      proinflammatory cytokines, interleukin (IL)-1beta (15 microg/kg) and tumor
      necrosis factor (TNF)-alpha (10 microg/kg), on food and water intake, locomotor
      activity, oxygen consumption (VO2), and respiratory exchange ratio (RER) was
      evaluated. The two cytokines elicited a comparable decrease in food intake and
      activated similar numbers of cells in the paraventricular nucleus of the
      hypothalamus (PVH), a region that plays a critical role in the regulation of
      appetite and metabolism (determined via expression of the immediate early gene, c
      fos). However, only IL-1beta reduced locomotion and RER, and increased VO2, while
      TNF-alpha was without effect. To examine the role of the melanocortins in
      mediating IL-1beta- induced metabolic changes, animals were pretreated centrally
      with a melanocortin receptor antagonist, HS014. Pretreatment with HS014 blocked
      the effect of IL-1beta on food intake and RER at later time points (beyond 8 h
      post injection), as well as the hypoactivity and increased metabolic rate.
      Further, HS014 blocked the induction of Fos-ir in the PVH. These data highlight
      the importance of the melanocortin system, particularly within the PVH, in
      mediating a broad range of metabolic responses to IL-1beta.

PMID- 18082229
TI  - Propofol enhances both tonic and phasic inhibitory currents in second-order
      neurons of the solitary tract nucleus (NTS).
AB  - The anesthetic propofol is thought to induce rapid hypnotic sedation by
      facilitating a GABAergic tonic current in forebrain neurons. The depression of
      cardiovascular and respiratory regulation often observed during propofol suggests
      potential additional actions within the brainstem. Here we determined the impacts
      of propofol on both GABAergic and glutamatergic synaptic mechanisms in a class of
      solitary tract nucleus (NTS) neurons common to brainstem reflex pathways. In
      horizontal brainstem slices, we recorded from NTS neurons directly activated by
      solitary tract (ST) axons. We identified these second-order NTS neurons by time
      invariant ("jitter"<200 micros), "all-or-none" glutamatergic excitatory
      postsynaptic currents (EPSCs) in response to shocks to the ST. In order to assess
      propofol actions, we measured ST-evoked, spontaneous and miniature EPSCs and
      inhibitory postsynaptic currents (IPSCs) during propofol exposure. Propofol
      prolonged miniature IPSC decay time constants by 50% above control at 1.8 microM.
      Low concentrations of gabazine (SR-95531) blocked phasic GABA currents. At higher
      concentrations, propofol (30 microM) induced a gabazine-insensitive tonic current
      that was blocked by picrotoxin or bicuculline. In contrast, total propofol
      concentrations up to 30 microM had no effect on EPSCs. Thus, propofol enhanced
      phasic GABA events in NTS at lower concentrations than tonic current induction,
      opposite to the relative sensitivity observed in forebrain regions. These data
      suggest that therapeutic levels of propofol facilitate phasic (synaptic)
      inhibitory transmission in second-order NTS neurons which likely inhibits
      autonomic reflex pathways during anesthesia.

PMID- 18082231
TI  - Expression and significance of PTEN in canine mammary gland tumours.
AB  - To explore the expression and clinical importance of the anti-oncogene
      phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in canine
      mammary gland tumours, PTEN expression was compared in 50 cases of canine mammary
      tumour and four examples of normal mammary tissue using real-time quantitative
      PCR. PTEN expression was similar in benign mammary tumours and normal mammary
      tissues (P>0.05), but was lower in malignant tumours than in normal mammary
      tissues or benign mammary tumours (P<0.001). PTEN expression was also low in the
      lymph node metastases of malignant mammary tumours. The expression profile of
      PTEN in malignant mammary tumours compared to those without lymph node metastasis
      varied significantly. Low-level PETN expression might play an important role in
      carcinogenesis and the progression of canine mammary tumours, and PTEN protein
      detection might be useful in evaluating tumour development and prognosis.

PMID- 18082230
TI  - Brown adipose tissue sympathetic nerve activity is potentiated by activation of 5
      hydroxytryptamine (5-HT)1A/5-HT7 receptors in the rat spinal cord.
AB  - In urethane-chloralose anesthetized, neuromuscularly blocked, ventilated rats,
      microinjection of NMDA (12 pmol) into the right fourth thoracic segment (T4)
      spinal intermediolateral nucleus (IML) immediately increased ipsilateral brown
      adipose tissue (BAT) sympathetic nerve activity (SNA; peak +492% of control),
      expired CO2 (+0.1%) heart rate (+48 beats min(-1)) and arterial pressure (+8
      mmHg). The increase in BAT SNA evoked by T4 IML microinjection of NMDA was
      potentiated when it was administered immediately following a T4 IML
      microinjection of 5-hydroxytryptamine (5-HT, 100 pmol) or the 5-HT1A/5-HT7
      receptor agonist, 8-OH-DPAT (600 pmol), (area under the curve: 184%, and 259% of
      the NMDA-only response, respectively). In contrast, T4 IML microinjection of the
      5-HT2 receptor agonist, DOI (28 pmol) did not potentiate the NMDA-evoked increase
      in BAT SNA (101% of NMDA-only response). Microinjection into the T4 IML of the
      selective 5-HT1A antagonist, WAY-100635 (500 pmol), plus the 5-HT7 antagonist, SB
      269970 (500 pmol), prevented the 5-HT-induced potentiation of the NMDA-evoked
      increase in BAT SNA. When administered separately, WAY-100635 (800 pmol) and SB
      269970 (800 pmol) attenuated the 8-OH-DPAT-induced potentiation of the NMDA
      evoked increase in BAT SNA through effects on the amplitude and duration of the
      response, respectively. The selective 5-HT2 receptor antagonist, ketanserin (100
      pmol), did not attenuate the potentiations of the NMDA-evoked increase in BAT SNA
      induced by either 5-HT or 8-OH-DPAT. These results demonstrate that activation of
      5-HT1A/5-HT7 receptors can act synergistically with NMDA receptor activation
      within the IML to markedly increase BAT SNA.

PMID- 18082232
TI  - [Efficacy of specific physiotherapy for temporomandibular joint dysfunction of
      muscular origin].
AB  - INTRODUCTION: Little explanation is given to patients with temporomandibular
      disorders and muscles dysfunction on the mechanism and the expected results of
      conservative treatment. The purpose of this prospective study was to evaluate the
      efficacy of specific physical therapy prescribed after this explanation was given
      and also after using a flat occlusal splint adapted only if muscle pain remained
      after physical therapy. MATERIAL AND METHOD: Twenty-seven patients with
      temporomandibular joint dysfunction of muscular origin were evaluated after a
      mean of six sessions of specialized physical therapy with professionals. Patients
      were treated by oral and facial massages and were trained for self-reeducation.
      They were also trained for a specific exercise named the "propulsive/opening
      maneuver". Every patient was questioned on the subjective evolution of pain and
      the current maximal pain was evaluated with the Visual Analogical Scale (VAS).
      Clinical evaluation focused on tenderness of masticator muscles and also assessed
      the changes in the amplitude of mouth opening. RESULTS: Ninety-three percent of
      the patients treated by specific physical therapy had a significant reduction of
      their maximal pain feeling (p<0.05). The recovery of an optimal mouth opening
      without deviation was also improved as was the protrusion. For 33% of the
      patients a flat nighttime occlusal splint was necessary as a complementary
      treatment. Twenty-two percent of the patients decided to change their treatment
      for alternative therapies (osteopathy, acupuncture, etc.). Fifty percent of the
      patients were convinced of the efficacy of the prescribed treatment. DISCUSSION:
      Patients who undertake the specific physical therapy and who regularly practice
      self-physical therapy succeed in relaxing their masticator muscles and in
      decreasing the level of pain. Explanations given by the doctor concerning the
      etiology of pain, during temporomandibular joint dysfunction of muscular origin,
      and the purpose of specific physical therapy increase the capacity of self
      relaxation. A flat occlusal splint is indicated for patients who grind their
      teeth and for those whose pain resists to physical therapy.

PMID- 18082233
TI  - Antimalarial resistance and DHFR/DHPS genotypes of Plasmodium falciparum three
      years after introduction of sulfadoxine-pyrimethamine and amodiaquine in rural
      Tanzania.
AB  - We assessed the efficacy of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ)
      and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania, 3 years after
      their introduction as first- and second-line treatments for uncomplicated
      malaria, respectively. Under five children with uncomplicated malaria were given
      standard treatments of either SP (n=66) or AQ (n=30) and treatment outcomes after
      14 and 28 days were determined. Total treatment failure of 18 and 42.5% was
      observed for SP on days 14 and 28, respectively. For AQ, total treatment failure
      of 27 and 53% was found on day 14 and 28, respectively. On day 14, significantly
      lower SP total treatment failures were observed in 2004 compared with results
      from a study conducted in 1999 in the same location. No relationship was detected
      between clinical outcome and DHFR/DHPS genotypes, but the point mutation
      prevalence in parasites was higher than in 1999. Pre-treatment blood levels of SP
      were detected in a quarter of the study children: less than expected. We report
      unacceptably high levels of total treatment failures, both for first- and second
      line treatments for uncomplicated malaria in Tanzania 3 years after their
      introduction, supporting the decision to replace them with artemisinin-based
      combination therapy.

PMID- 18082234
TI  - Diagnostic value of nodule palpation in onchocerciasis.
AB  - Nodule palpation is the major diagnostic tool for determining the prevalence of
      infection in areas of the African Programme for Onchocerciasis Control (APOC) and
      is recommended for identifying communities at risk and selecting them for mass
      drug administration. The diagnostic value of palpation, however, has not been
      quantified in terms of sensitivity and predictive values. We derive these
      measures from the probability that a nodule is palpable, which has been estimated
      by stochastic simulations from an extensive pre-control database. We show that
      nodule palpation is only reliable in highly endemic areas and that false-positive
      diagnoses can lead to considerable misclassifications of regions where endemicity
      is actually low. Its diagnostic precision is poor because of large intra- and
      inter-individual variability. The findings underline the need for further
      development of available diagnostics that allow long-term monitoring when
      endemicity declines.

PMID- 18082235
TI  - Enzyme-assisted synthesis and structure characterization of glucuronide
      conjugates of eleven anabolic steroid metabolites.
AB  - Enzyme-assisted in vitro synthesis of eleven glucuronide-conjugated anabolic
      androgenic steroid (AAS) metabolites was performed using biphenyl-induced rat
      liver microsomal enzymes. The substrates within the study were the main compounds
      and metabolites detected in human urine after dosing of, e.g. metandienone,
      metenolone, methyltestosterone, nandrolone, and testosterone. Yields of
      glucuronidation reactions were 13-28% for most compounds, but significantly
      higher (77-78%) for the substrates with 4-ene-3-one double bond system of the
      steroid A-ring. Characterization of glucuronide-conjugated AAS structures was
      based on nuclear magnetic resonance spectroscopy ((1)H NMR) and on liquid
      chromatographic-mass spectrometric (LC-MS) and tandem mass spectrometric (LC
      MS/MS) analyses in positive and negative ion mode electrospray ionization (ESI).
      Only minor differences were observed in optimal synthesis conditions between
      various substrates, which offer a potential to apply this in vitro assay as a
      default method for glucuronidation of new AAS substrates. The method allowed for
      a rapid production pathway of stereochemically pure AAS glucuronides in milligram
      amount, such as needed, e.g. in the development of analytical methods in forensic
      or pharmaceutical sciences, as well as in doping control.

PMID- 18082237
TI  - Membrane fluidity altering and enzyme inactivating in sarcoma 180 cells post the
      exposure to sonoactivated hematoporphyrin in vitro.
AB  - Sonodynamic therapy (SDT) is a novel tumor therapy method. We investigated
      membrane fluidity, activity of the enzymes and membrane morphology in vitro post
      hematoporphyrin-SDT treatment. Furthermore, the potential mechanisms behind the
      changes in membrane fluidity and enzymic activity were discussed. Tumor cells
      were exposed to ultrasound at 1.75 MHz for up to 3 min in the presence and
      absence of hematoporphyrin. Fluorescence polarization, contents of Malonaldehyde,
      and levels of free fatty acid were assessed. Activity of enzymes was checked by
      the plumbic nitrate detection method. For the morphologic study, a scanning
      electron microscope was used to observe the cellular surface. Ultrasonically
      induced cell damage increased in the presence of HPD (from 15% to 24%). Compared
      with ultrasound treatment alone, the fluidity decreased from 5.037 to 3.908,
      malonaldehyde content and free fatty acid level increased from 0.743 nmol/mL to
      0.97 9 nmol/mL and from 237.180 micromol/L to 730.769 micromol/L, respectively,
      post ultrasound combined with HPD treatment. Inactivity of adenylate cyclase and
      guanylate cyclase and significant deformation of the cellular surface were also
      observed post SDT treatment. Our results suggested that alterations in membrane
      modality and lipid composition played important roles in SDT-mediated inhibition
      of tumor growth, even inducing tumor cell death, which might be attributed to a
      sono-chemical activation mechanism.

PMID- 18082236
TI  - Ultrasound simulation of real-time temperature estimation during radiofrequency
      ablation using finite element models.
AB  - Radiofrequency ablation is the most common minimally invasive therapy used in the
      United States to treat hepatocellular carcinoma and liver metastases. The ability
      to perform real-time temperature imaging while a patient is undergoing ablation
      therapy may help reduce the high recurrence rates following ablation therapy.
      Ultrasound echo signals undergo time shifts with increasing temperature due to
      sound speed and thermal expansion, which are tracked using both 1D cross
      correlation and 2D block matching based speckle tracking methods. In this paper,
      we present a quantitative evaluation of the accuracy and precision of temperature
      estimation using the above algorithms on both simulated and experimental data. A
      finite element analysis simulation of radiofrequency ablation of hepatic tissue
      was developed. Finite element analysis provides a method to obtain the exact
      temperature distribution along with a mapping of the tissue displacement due to
      thermal expansion. These local displacement maps were combined with the
      displacement due to speed of sound changes and utilized to generate ultrasound
      radiofrequency frames at specified time increments over the entire ablation
      procedure. These echo signals provide an ideal test-bed to evaluate the
      performance of both speckle tracking methods, since the estimated temperature
      results can be compared directly to the exact finite element solution. Our
      results indicate that the 1D cross-correlation (CC) method underestimates the
      cumulative displacement by 0.20mm, while the underestimation with 2D block
      matching (BM) is about 0.14 mm after 360 s of ablation. The 1D method also
      overestimates the size of the ablated region by 5.4% when compared to 2.4% with
      the 2D method after 720 s of ablation. Hence 2D block matching provides better
      tracking of temperature variations when compared to the 1D cross-correlation
      method over the entire duration of the ablation procedure. In addition, results
      obtained using 1D cross-correlation diverge from the ideal finite element results
      after 7 min of ablation and for temperatures greater than 65 degrees C. In a
      similar manner, experimental results presented using a tissue-mimicking phantom
      also demonstrate that the maximum percent difference with 2D block matching was
      5%, when compared to 31% with the 1D method over the 700 s heating duration on
      the phantom.

PMID- 18082238
TI  - Effects of perceptual learning on primary visual cortex activity in humans.
AB  - Psychophysical and neuroimaging studies suggest that perceptual learning may
      affect activity in primary visual cortex (V1). Yet, it remains unclear whether
      such changes involve intrinsic V1 plasticity or feedback from later processing
      stages. Here we recorded high-density electro-encephalography in 24 volunteers,
      24-h after training on a visual texture discrimination task in the upper or lower
      visual-field. Post-training improvement in upper visual-field was associated with
      changes in early visual responses, starting 40ms post-stimulus, with reduced
      amplitude of retinotopic C1, known to reflect V1 activity. No behavioral or
      neurophysiological effect was found after training in lower visual-field,
      suggesting retinotopic constraints on perceptual learning. Our results
      demonstrate that successful acquisition of a perceptual skill can produce long
      lasting changes for initial sensory inputs in the adult human visual system.

PMID- 18082239
TI  - Eccentric grouping by proximity in multistable dot lattices.
AB  - The Pure Distance Law predicts grouping by proximity in dot lattices that can be
      organised in four ways by grouping dots along parallel lines. It specifies a
      quantitative relationship between the relative probability of perceiving an
      organisation and the relative distance between the grouped dots. The current
      study was set up to investigate whether this principle holds both for centrally
      and for eccentrically displayed dot lattices. To this end, dot lattices were
      displayed either in central vision, or to the right of fixation with their
      closest border at 3 degrees or 15 degrees. We found that the Pure Distance Law
      adequately predicted grouping of centrally displayed dot lattices but did not
      capture the eccentric data well, even when the eccentric dot lattices were
      scaled. Specifically, a better fit was obtained when we included the possibility
      in the model that in some trials participants could not report an organisation
      and consequently responded randomly. A plausible interpretation for the
      occurrence of random responses in the eccentric conditions is that under these
      circumstances an attention shift is required from the locus of fixation towards
      the dot lattice, which occasionally fails to take place. When grouping could be
      reported, scale and eccentricity appeared to interact. The effect of the relative
      interdot distances on the perceptual organisation of the dot lattices was
      estimated to be stronger in peripheral vision than in central vision at the two
      largest scales, but this difference disappeared when the smallest scale was
      applied.

PMID- 18082240
TI  - Extracellular proteins, polysaccharides and enzymes impact on sludge aerobic
      digestion after ultrasonic pretreatment.
AB  - Ultrasonic pretreatment of excess sludge can improve its aerobic digestibility,
      leading to enhanced sludge reduction. In order to understand the mechanisms of
      this improvement, sludge flocs were divided into four layers, i.e. (1) slime, (2)
      loosely bound extracellular polymeric substances (LB-EPS), (3) tightly bound EPS
      (TB-EPS) and (4) pellet. Extracellular proteins, polysaccharides and five types
      of hydrolytic enzymes (protease, alpha-amylase, alpha-glucosidase, alkaline
      phosphatase and acid-phosphatase) from sludge flocs were investigated to
      determine their influence on sludge aerobic digestion after ultrasonic
      pretreatment. Results suggested that most of the extracellular enzymes (except
      alpha-amylase) were present in pellet and TB-EPS layers, with minor quantities
      detected in LB-EPS and slime layers, and almost none detected in bulk solution.
      As for alpha-amylase in sludge flocs, most of it (52.6%) was also mainly bound
      with pellet; however, the rest of it was dispersed nearly uniformly throughout
      the sludge flocs. Ultrasonic pretreatment enhances enzymatic activities and
      promotes the shifts of extracellular proteins, polysaccharides and enzymes from
      inner layers of sludge flocs, i.e., pellet and TB-EPS, to outer layers, i.e.,
      slime, to increase the contact and interaction among extracellular proteins,
      polysaccharides and enzymes that were originally embedded in the sludge flocs,
      resulting in improved efficiency in aerobic digestion. The optimum ultrasonic
      pretreatment conditions had a lasting time of 10min and density of 3 kWL(-1) at
      the frequency of 20 kHz. With the optimum ultrasonic pretreatment, the sludge
      reduction for TSS in aerobic digestion was 42.7% in which the part of 11.8% was
      removed by the ultrasonic pretreatment, compared with 20.9% for control, after an
      aerobic digestion time of 10.5d.

PMID- 18082241
TI  - Modeling the removal of dissolved organic carbon by ion exchange in a completely
      mixed flow reactor.
AB  - A mathematical model was developed to describe removal of dissolved organic
      carbon (DOC) by a macroporous, strong-base anion exchange resin in a completely
      mixed flow reactor with resin recycle and partial resin regeneration. The two
      scale model consisted of a microscale model describing the uptake of DOC by the
      resin coupled with a macroscale model describing the continuous-flow process.
      Equilibrium and kinetic parameters were estimated from batch laboratory
      experiments. The model was validated using continuous-flow data from two pilot
      plant studies. Model predictions were found to be in good agreement with the
      observed pilot plant data.

PMID- 18082242
TI  - Statistical assessment of the accuracy and precision of bacteria- and virus-sized
      microsphere enumerations by epifluorescence microscopy.
AB  - Fluorescent microspheres are increasingly used in environmental studies to
      evaluate threats of viral and bacterial pathogens in drinking water and to
      investigate colloid-facilitated contaminant transport. A commonly accepted
      technique for the enumeration of viruses, bacteria, and virus- and bacteria-sized
      particles by microscopy involves a field-of-view (field) approach to estimate
      concentration. Few studies have focused on those factors that are most important
      in ensuring precise and accurate measures of concentration. Microsphere counts in
      suspensions of artificial groundwater and deionized water were contrasted in this
      study to gain a greater understanding of the effect of ionic strength and the
      presence of precipitates in groundwater matrices that can bias microsphere
      enumerations. To investigate microsphere enumeration with minimal bias from other
      factors, a commonly used standard method was used to prepare slides and enumerate
      microspheres, with particular care to randomly select fields for counting. A
      factorial experiment evaluated two factors, (1) the density of microspheres in
      each field and (2) the number of counts in an enumeration. Two parameters,
      relative standard deviation and percent error, were used to assess methodological
      precision and accuracy. Visual observations of the slides indicated that some
      biases, such as undulation in the filter membrane or bubble entrained in the
      mounting medium, create biases in microsphere enumeration. Additional biases were
      introduced by the presence of precipitates that form in artificial groundwater
      saturated with calcite. Microsphere density was found to be critical for ensuring
      methodological precision, whereas the total number of microspheres counted was
      essential to ensuring methodological accuracy. The results suggested that to
      minimize variability using the field approach, the enumeration of at least 350
      microspheres and 25-40 microspheresfield (-1) is necessary.

PMID- 18082243
TI  - Comment on "Evaluating landfill disposal of chromated copper arsenate (CCA)
      treated wood and potential effects on groundwater: Evidence from Florida" by
      Jennifer K. Saxe, Eric J. Wannamaker, Scott W. Conklin, Todd F. Shupe and Barbara
      D. Beck [Chemosphere 66 (3) (2007) 496-504].

PMID- 18082244
TI  - Traffic and catalytic converter - related atmospheric contamination in the
      metropolitan region of the city of Rio de Janeiro, Brazil.
AB  - In this work, 24-h PM10 samples were collected in Rio de Janeiro, Brazil, and
      analysed for trace elements (Cd, Ce, Cu, La, Mo, Ni, Pb, Pd, Rh, Sb and Sn). The
      sampling was carried out at five locations (Bonsucesso; Centro, downtown city;
      Copacabana; Nova Iguacu and Sumare) with different traffic densities and
      anthropogenic activities. An analytical method based on the EPA method for the
      determination of trace elements in airborne particulate matter (PM), using
      ultrasonic-assisted extraction and inductively coupled plasma mass spectrometry
      (ICP-MS) was applied. Our results suggest that vehicular traffic is the most
      important source of environmental pollution at the studied sites. The presence of
      Mo, Pd and Rh in the analysed filters reflects an additional source of pollution
      caused by the erosion and deterioration of automotive catalytic converters.

PMID- 18082245
TI  - Comparison of microbial indicators under two water regimes in a soil amended with
      combined paper mill sludge and decomposed cow manure.
AB  - An incubation study was conducted under laboratory conditions to compare the
      effects of soil amendment of combined paper mill sludge (PS) and decomposed cow
      manure (DCM) on selected microbial indicators. A lateritic soil (Typic
      Haplustalf) was amended with 0 (control), 20 or 80tha(-1) (wet weight) of PS or
      DCM. The amended soils were then adjusted to 60% water holding capacity (WHC) or
      submerged conditions, and incubated at 27 degrees C in dark for up to 120days
      (d). The microbial biomass C (MBC), the basal soil respiration and the enzyme
      activities of the beta-glucosidase, acid phosphatase and sulphatase were analyzed
      at day 15, 30, 45, 60 and 120. Compared to the unamended soil (control), the MBC,
      the basal soil respiration and the enzyme activities increased with the rate of
      PS and DCM. At similar rate, the DCM treatment increased significantly the MBC,
      the soil respiration and the enzyme activities compared to the PS treatment.
      Also, the water regimes affected the microbial activities. At 60% WHC, the MBC
      and soil respiration increased during the first 30d and decreased thereafter. The
      enzyme activities showed similar trends, where they increased for the first 60d,
      and decreased thereafter. In contrast, under submerged condition, the MBC and
      enzymes activities declined during 120d, whereas the soil respiration increased.
      Compared to the control, the used of PS and DCM had no negative impact of the
      soil microbial parameters, even at the highest application rate. Long-term field
      experiments are required to confirm these laboratory results.

PMID- 18082246
TI  - Second generation anticoagulant rodenticides in tawny owls (Strix aluco) from
      Great Britain.
AB  - Secondary exposure of vertebrate predators to second generation anticoagulant
      rodenticides (SGARs) is widespread in Britain. Tawny owl (Strix aluco)
      populations in the UK are thought to have declined since the 1970s, when SGARs
      were first introduced, and these compounds may have contributed to any decline in
      owl numbers. Our aims were to conduct the first systematic survey of SGAR
      exposure in tawny owls and ascertain whether there had been a change in the
      proportion of exposed birds that was concurrent with the decline in the
      population. Liver difenacoum, bromadiolone, flocoumafen and brodifacoum
      concentrations in British tawny owls from two periods (1990-1993 and 2003-2005)
      were quantified. In total, some 20% of birds contained detectable residues of one
      or more SGAR. The extent of exposure (% of birds exposed, magnitude of residues)
      to different SGARs did not change consistently between time periods. Of the
      raptors analysed to date in Britain, tawny owls had the lowest proportion of
      individuals that contained detectable liver residues and so appear to be the
      least vulnerable to exposure and/or assimilation of SGARs. We found no clear
      evidence to implicate SGARs as a major factor affecting tawny owl numbers in
      Britain between 1990 and 2005.

PMID- 18082247
TI  - Development of an innovative soil remediation: "Cyclodextrin-enhanced combined
      technology".
AB  - This paper introduces an in situ "Cyclodextrin-enhanced soil bioremediation
      technology" which is a combination of 1. in situ bioventilation for
      biodegradation in the unsaturated soil zone; 2. physico-chemical treatment of the
      pumped ground water; 3. impulsive flushing for the three-phase soil. For
      enhancement of biodegradation and solubilization randomly methylated beta
      cyclodextrin (RAMEB) was used. An additional aim of this study was to prove the
      importance of the technology monitoring which was used for characterisation of
      the soil processes by an integrated methodology. It consists of physico-chemical,
      biological and ecotoxicological methods specific for the contaminants. For
      technology monitoring the mobile soil phases--soil gas and ground water--were
      analysed. Sampling of the whole soil was carried out at the start and end of the
      technology application. RAMEB resulted in the enhanced removal of pollutants both
      from the saturated and unsaturated soil zones. Moreover, the biodegradation was
      more effective than the pump and treat technology, proved by the establishment of
      the carbon material balance in all soil phases.

PMID- 18082248
TI  - Histological comparison of bone induced from autogenously grafted periosteum with
      bone induced from autogenously grafted bone marrow in the rat calvarial defect
      model.
AB  - Both periosteum and bone marrow have the potential to induce heterotopic bone
      when grafted. Whether the process of bone formation is controlled by the
      recipient environment where the donor graft is placed or by factors from the
      donor site is not well documented. The purpose of this study was to examine the
      histology of new bone induced by either autogenously grafted periosteum or
      autogenously grafted bone marrow using the rat calvarial defect model in Sprague
      Dawley rats. Grafts of either bone marrow or periosteum obtained from tibias were
      placed in calvarial defects with beta-tricalcium phosphate. Ten days after
      grafting, active cell proliferation was observed in the defects of both types of
      grafts. After 20 days, cancellous bone formation was observed in the defects with
      bone marrow grafts, and intramembranous bone formation was observed in the
      defects with periosteal grafts. After 30 days, bone marrow grafts had developed
      bone with a bone marrow-like structure, and the periosteal grafts had produced
      cortical bone structure in the defects. The findings suggest that the type of
      bone formation is determined by characteristics of the donor site.

PMID- 18082249
TI  - Detection of viral genomes of caprine arthritis-encephalitis virus (CAEV) in
      semen and in genital tract tissues of male goat.
AB  - The aim of this study was to determine the infectious status of semen and genital
      tract tissues from male goat naturally infected with the caprine lentivirus.
      Firstly, polymerase chain reaction (PCR) was used to detect the presence of CAEV
      proviral-DNA in the circulating mononuclear cells, semen (spermatozoa and non
      spermatic cells), and genital tract tissues (testis, epididymis, vas deferens,
      and vesicular gland) of nine bucks. RT-PCR was used to detect the presence of
      CAEV viral RNA in seminal plasma. Secondly, in situ hybridization was performed
      on PCR-positive samples from the head, body, and tail of the epididymis. CAEV
      proviral-DNA was identified by PCR in the blood cells of 7/9 bucks and in non
      spermatic cells of the seminal plasma of 3/9 bucks. No CAEV proviral-DNA was
      identified in the spermatozoa fraction. The presence of CAEV proviral-DNA in non
      spermatic cells and the presence of CAEV in the seminal plasma was significantly
      higher (p<0.01) in bucks with PCR-positive blood. Two of the three bucks with
      positive seminal plasma cells presented with at least one PCR-positive genital
      tract tissue. Proviral-DNA was found in the head (3/9), body (3/9), and tail
      (2/9) of the epididymis. In situ hybridization confirmed the presence of viral
      mRNA in at least one of each of these tissues, in the periphery of the epididymal
      epithelium. This study clearly demonstrates the presence of viral mRNA and
      proviral-DNA in naturally infected male goat semen and in various tissues of the
      male genital tract.

PMID- 18082250
TI  - Mirror neurons in humans: consisting or confounding evidence?
AB  - The widely known discovery of mirror neurons in macaques shows that premotor and
      parietal cortical areas are not only involved in executing one's own movement,
      but are also active when observing the action of others. The goal of this essay
      is to critically evaluate the substance of functional magnetic resonance imaging
      (fMRI) and positron emission tomography (PET) studies whose aim has been to
      reveal the presence of a parallel system in humans. An inspection of this
      literature suggests that there is relatively weak evidence for the existence of a
      circuit with 'mirror' properties in humans, such as that described in monkeys.

PMID- 18082251
TI  - Sedimentary and water column processes in the Oyster Grounds: a potentially
      hypoxic region of the North Sea.
AB  - The purpose of this research was to investigate the potential causes of low
      oxygen levels in the bottom water of the Oyster Grounds region of the shallow
      southern North Sea, an area which provides suitable conditions for low oxygen
      levels to develop. At the end of the summer stratified period, relevant
      biogeochemical processes were investigated using a combination of sedimentary and
      water column rate measurements. Phytoplankton nitrate and ammonium uptake was
      measured throughout the water column using (15)N labelled isotopes and showed
      ammonium uptake dominated in the upper and bottom mixed layer with a maximum
      294.4 micromol N m(-3)h(-1). In the deep chlorophyll maximum at the thermocline,
      primary production was dominated by nitrate uptake, with an average of 35.0
      micromol N m(-3)h(-1), relative to ammonium uptake, with an average of 24.6
      micromol N m(-3)h(-1). This high relative nitrate uptake will in part result in
      exportable new production to the isolated bottom mixed layer and sediments, as
      opposed to regenerated ammonium driven uptake. This biomass export was indicated
      by significant benthic oxygen consumption rates in the stratified region (782
      1275 micromol O(2)m(-2)h(-1)micromol N m(-3)h(-1)) long after the end of the
      spring bloom. The sediments were also an active net source of nitrate, ammonium,
      phosphate and silicate into the bottom mixed layer of 4.4, 8.4, 2.3 and 68.8
      micromol m(-2)h(-1), respectively. The export of new production within the
      thermocline to the bottom mixed layer and the consequent sediment oxygen
      consumption in the isolated bottom mixed layer in the Oyster Grounds are expected
      to have contributed to the low bottom water oxygen concentrations of 2.07 mg l(
      1) (64.7 micromol l(-1)) measured. The long stratified period associated with
      this low oxygen is predicted to occur more regularly in the future and continued
      monitoring of this ecologically important region is therefore essential if the
      causes of these potentially damaging low oxygen levels are to be fully
      understood.

PMID- 18082252
TI  - Distribution of DDT and other persistent organic contaminants in Canyons and on
      the continental shelf off the central California coast.
AB  - Sediment samples were collected to delineate the distribution of contaminants
      along the central California coast. Sampling included a variety of Canyons and
      shelf/slope areas to evaluate contaminant transport patterns and potential
      delivery to Canyons and the continental slope to a depth of 1200 m. Sediments
      were collected and analyzed for organic contaminants using standard techniques of
      the NOAA National Status and Trends Program (NS&T). DDT is distributed on the
      shelf within a zone of fine-grained sediments between Half Moon and Monterey
      Bays. DDT was found at higher concentrations in Ascension, Ano Nuevo, and
      Monterey/Soquel Canyons than in Pioneer and Carmel Canyons, the Gulf of the
      Farallones, or the continental slope. The Monterey Bay watershed appears to be
      the primary source of DDT. In contrast, PAHs and PCBs on the shelf appear to be
      derived primarily from San Francisco Bay. DDT appears to be delivered to the deep
      ocean via the Canyons more than from cross-shelf sediment transport. Sediment
      budget estimates for the continental shelf north of Monterey Bay need further
      refinement and more data to account for the movement of material from Monterey
      Bay onto the shelf.

PMID- 18082253
TI  - Mechanical properties of single electrospun collagen type I fibers.
AB  - The mechanical properties of single electrospun collagen fibers were investigated
      using scanning mode bending tests performed with an AFM. Electrospun collagen
      fibers with diameters ranging from 100 to 600 nm were successfully produced by
      electrospinning of an 8% w/v solution of acid soluble collagen in 1,1,1,3,3,3
      hexafluoro-2-propanol (HFP). Circular dichroism (CD) spectroscopy showed that 45%
      of the triple helical structure of collagen molecules was denatured in the
      electrospun fibers. The electrospun fibers were water soluble and became
      insoluble after cross-linking with glutaraldehyde vapor for 24h. The bending
      moduli and shear moduli of both non- and cross-linked single electrospun collagen
      fibers were determined by scanning mode bending tests after depositing the fibers
      on glass substrates containing micro-channels. The bending moduli of the
      electrospun fibers ranged from 1.3 to 7.8 GPa at ambient conditions and ranged
      from 0.07 to 0.26 MPa when immersed in PBS buffer. As the diameter of the fibrils
      increased, a decrease in bending modulus was measured clearly indicating
      mechanical anisotropy of the fiber. Cross-linking of the electrospun fibers with
      glutaraldehyde vapor increased the shear modulus of the fiber from approximately
      30 to approximately 50 MPa at ambient conditions.

PMID- 18082254
TI  - The use of charge-coupled polymeric microparticles and micromagnets for
      modulating the bioavailability of orally delivered macromolecules.
AB  - Protein drugs have low bioavailability after oral administration, which is due in
      part to fast transit of the drugs or drug delivery vehicles through the
      gastrointestinal tract. Increasing the time that the drugs spend in the intestine
      after dosing would allow for greater absorption and increased bioavailability. We
      developed a formulation strategy that can be used to prolong intestinal retention
      of drug delivery vehicles without substantial alterations to current polymeric
      encapsulation strategies. A model drug, insulin, was encapsulated in negatively
      charged poly(lactic-co-glycolic acid) (PLGA) microparticles, and the
      microparticles were subsequently mixed with positively charged micromagnets,
      whose size will prevent them from being absorbed. Stable complexes formed through
      electrostatic interaction. The complexes were effectively immobilized in vitro in
      a model of the mouse small intestine by application of an external magnetic
      field. Mice that were gavaged with radio-labeled complexes and fitted with a
      magnetic belt retained 32.5% of the (125)I-insulin in the small intestine
      compared with 5.4% for the control group 6h after administration (p=0.005).
      Furthermore, mice similarly gavaged with complexes encapsulating insulin (120
      Units/kg) exhibited long-term glucose reduction in the groups with magnetic
      belts. The corresponding bioavailability of insulin was 5.11% compared with 0.87%
      for the control group (p=0.007).

PMID- 18082255
TI  - Cytokine signaling, inflammation, innate immunity and preterm labour - a workshop
      report.

PMID- 18082256
TI  - Overexpression of stem cell associated ALDH1A1, a target of the leukemogenic
      transcription factor TLX1/HOX11, inhibits lymphopoiesis and promotes myelopoiesis
      in murine hematopoietic progenitors.
AB  - TLX1/HOX11 is an oncogenic transcription factor in human T-cell leukemia,
      however, the molecular basis for its transforming activity has remained elusive.
      The ALDH1A1 gene, whose product participates in retinoic acid synthesis, was
      previously identified as a TLX1-responsive gene. Here, we confirm regulation of
      ALDH1A1 transcription by TLX1 and show that ALDH1A1 can profoundly perturb murine
      hematopoiesis by promoting myeloid differentiation at the expense of
      lymphopoiesis. Together, these data demonstrate that ALDH1A1 plays a key role in
      normal hematopoiesis, and confirm ALDH1A1 as a TLX1 transcriptional target that
      may contribute to the ability of this homeoprotein to alter cell fate and induce
      tumor growth.

PMID- 18082257
TI  - Phase II clinical trial of arsenic trioxide with liposomal doxorubicin,
      vincristine, and dexamethasone in newly diagnosed multiple myeloma.
AB  - In patients with multiple myeloma, there is preclinical justification to combine
      arsenic trioxide (ATO and As(2)O(3)) with DVd (Doxiltrade mark, vincristine, and
      dexamethasone) for newly diagnosed patients. Eleven patients on this phase II
      trial received 0.15 mg/kg of ATO for five consecutive days followed by four
      cycles of DVd plus ATO with the ATO at 0.25mg/kg IV twice per week. The most
      common grade 3 toxicities were hyperglycemia, hyponatremia, and hypocalcemia.
      There were four partial and no complete responses. We could not demonstrate that
      the addition of ATO with this schedule improved the response rate of MM to DVd.

PMID- 18082258
TI  - Are mouthwashes a reliable source of constitutional DNA in patients with
      leukemia?

PMID- 18082259
TI  - Physical abuse during adolescence: Gender differences in the adolescents'
      perceptions of family functioning and parenting.
AB  - OBJECTIVE: To examine the relationship between physical abuse of adolescents and
      parenting by mothers and fathers and whether the association differs by gender.
      METHODS: Subjects were adolescents, 51 girls and 45 boys, documented by Child
      Protective Services (CPS) as physically abused during adolescence. Comparison
      subjects were non-abused adolescents, 47 girls and 48 boys, from the same
      suburban communities. Subjects completed the following: Family Adaptability and
      Cohesion Evaluation Scale, Parental Bonding Instrument, modified Conflict Tactics
      Scale (assessing physical abuse/punishment by each parent). RESULTS: Although CPS
      generally cited fathers as the abuse perpetrators, abused boys and girls often
      reported experiencing physical maltreatment from both parents. Not surprisingly,
      comparison subjects rated parents more positively than abused subjects. For both
      groups, mothers were perceived as more caring and less controlling, were reported
      to have closer relationships with their adolescents, and were less likely to use
      abuse/harsh punishment than were fathers. Differences between the adolescents'
      perceptions of mothers and fathers were more pronounced for abused than for
      comparison subjects. Boys' and girls' perceptions of parenting were generally
      similar except that girls, especially the abused girls, reported feeling less
      close to fathers. Abused girls also viewed mothers as less caring than the other
      groups viewed mothers. Abused girls were also less likely than abused boys to
      perceive that either parent, but particularly fathers, had provided them with an
      optimum style of parenting. CONCLUSIONS: Adolescents who experienced relatively
      mild physical abuse reported dysfunctional family relationships, which may place
      them at risk of poor adult outcomes. Adolescents' reports suggest that CPS
      reports may underestimate physical maltreatment by mothers.

PMID- 18082261
TI  - The role of hemocytes in the immunity of the spider Acanthoscurria gomesiana.
AB  - Invertebrates protect themselves against microbial infection through cellular and
      humoral immune defenses. Since the available information on the immune system of
      spiders is scarce, the main goal of the present study was to investigate the role
      of hemocytes and antimicrobial peptides (AMPs) in defense against microbes of
      spider Acanthoscurria gomesiana. We previously described the purification and
      characterization of two AMPs from the hemocytes of naive spider A. gomesiana,
      gomesin and acanthoscurrin. Here we show that 57% of the hemocytes store both
      gomesin and acanthoscurrin, either in the same or in different granules.
      Progomesin labeling in hemocyte granules indicates that gomesin is addressed to
      those organelles as a propeptide. In vivo and in vitro experiments showed that
      lipopolysaccharide (LPS) and yeast caused the hemocytes to migrate. Once they
      have reached the infection site, hemocytes may secrete coagulation cascade
      components and AMPs to cell-free hemolymph. Furthermore, our results suggest that
      phagocytosis is not the major defense mechanism activated after microbial
      challenge. Therefore, the main reactions involved in the spider immune defense
      might be coagulation and AMP secretion.

PMID- 18082260
TI  - Interplay between childhood maltreatment, parental bonding, and gender effects:
      impact on quality of life.
AB  - OBJECTIVE: The aim of this study was to examine associations between childhood
      adversity, parental bonding, gender, depressive symptoms, and quality of life in
      non-treatment-seeking adults from the community. METHOD: Effects of differential
      parental rearing were compared in adults who reported a high degree of childhood
      maltreatment (n=72) and those who reported no significant adverse events in
      childhood (n=69). Subjects completed retrospective measures of childhood
      maltreatment and perceived parenting style, as well as measures of current
      depressive symptoms and quality of life. RESULTS: The subjects without childhood
      maltreatment were younger and endorsed less current depressive symptomatology
      than did subjects with childhood maltreatment. While the subjects without a
      history of maltreatment reported more "optimal" bonding experiences with their
      parents, the maltreatment group members were more likely to characterize their
      early parental bonding experiences in terms of "affectionless control" (p<.001
      for both maternal and paternal parenting), "affectionate constraint" (p=.025 for
      maternal parenting and p=.004 for paternal parenting), or "weak or absent"
      bonding (p<.001 for both maternal and paternal parenting). Results of a multiple
      regression analysis revealed that overall quality of paternal care (p=.015) and
      current level of depressive symptoms (p<.001) were significant independent
      predictors of adult quality of life. Gender effects between subjects providing
      parental bonding data were limited to the group with childhood maltreatment.
      CONCLUSION: These findings extend previous work documenting a relationship
      between early life maltreatment and suboptimal parental bonding, suggesting
      gender-specific effects of maternal and paternal care. Effects of childhood
      maltreatment on quality of life in adulthood appear to be linked with the quality
      of childhood paternal care and the occurrence of depressive symptomatology in
      adulthood, suggesting possible targets for primary or secondary prevention.

PMID- 18082262
TI  - TraM protein of plasmid R1: in vitro selection of the target region reveals two
      consensus 7 bp binding motifs spaced by a 4 bp linker of defined sequence.
AB  - The TraM protein encoded by plasmid R1 has three functions in conjugative
      transfer: (i) it positively controls transfer gene expression, (ii) it stimulates
      efficient site-specific ssDNA cleavage at the oriT in vivo and (iii) it couples
      the relaxosome to the envelope-bound transport complex. Plasmid R1 contains two
      binding regions for TraM, sbmA and sbmB, either of which comprises several
      minimal TraM targets. SELEX of a randomized minimal (18 bp) TraM binding sequence
      was used to search for sequences that bind TraM most efficiently. This approach
      resulted in a sequence with a modular structure with two 7 bp consensus motifs 5'
      T1G2A3N4T5C6R7 and 5' T1G2A3N4T5Y6R7 spaced by a 4 bp linker with the consensus
      sequence 5' Y1A2/C2T3/G3A4. EMSAs revealed that evolution in vivo was for maximal
      binding affinity. R1 derivatives with mutated sbmA and sbmB sites based on one in
      vitro selected sequence were found to be either 5-fold impaired (mut sbmA) in
      conjugation or could not be transferred by conjugation anymore (mut sbmB).
      Transcriptional lacZ fusions demonstrated that the introduced sbmB mutations
      affected promoter activity severely and abrogated autoregulation by TraM, thereby
      explaining this drastic effect on conjugal transfer. The implications of these
      findings are discussed in the context of the role of TraM.

PMID- 18082263
TI  - The role of phytochelatins and antioxidants in tolerance to Cd accumulation in
      Brassica juncea L.
AB  - A hydroponics experiment using Indian mustard (Brassica juncea L.) was conducted
      to investigate the effect of different concentrations (10-160 microM) of cadmium
      (Cd) and a fixed concentration (500 microM) of ethylene diamine tetra acetic acid
      (EDTA) on Cd accumulation and its toxicity for 14 and 28 days (d). The results
      showed that Cd alone and Cd+EDTA increased total dry biomass production,
      photosynthetic pigments and total protein content of B. juncea up to 160 microM
      with respect to control for 14d (hormesis effect). Further, on treatment with Cd
      at 160 microM for 28d, dry biomass of root and shoot, total protein content and
      total chlorophyll decreased up to 73%, 58%, 67% and 53% respectively, while in
      the case of Cd+EDTA, the decrease in the above parameters was 38%, 50%, 57% and
      46% with respect to their control. It was observed that the maximum Cd
      accumulation after 28d in the root and shoot was 1925 and 977 mg kg(-1) dry
      weight (dw), respectively, while in the case of Cd+EDTA it was 1013 and 2316 mg
      kg(-1)dw, respectively. Levels of phytochelatins (PCs), glutathione reductase
      (GR; EC 1.6.4.2), non-protein thiols (NP-SH) and glutathione (GSH) were monitored
      as plants primary and secondary metal detoxifying responses. Glutathione
      reductase showed three-fold increased activity for Cd and 2.2-fold for Cd+EDTA at
      160 microM after 14d followed by decreased activity after 28d with respect to
      control. Maximum synthesis of PCs was found at 10 microM of Cd exposure followed
      by a gradual decline after 28d. This may be correlated with reduced level of GSH,
      probably due to reduced GR activity, resulting in enhanced oxidative stress as
      also proved by phenotypic changes in plants such as browning of roots and
      yellowing of leaves. Thus, the capacity of B. juncea to accumulate and tolerate
      high concentrations of Cd, through enhanced level of PCs, GSH, NP-SH and GR
      suggests its applicability for phytoremediation.

PMID- 18082264
TI  - Comparison of toxicity of congener-153 of PCB, PBB, and PBDE to Daphnia magna.
AB  - Acute and reproductive toxicity tests were performed to assess the effects of two
      polybrominated flame retardants, polybrominated biphenyl (PBB)-153,
      polybrominated diphenyl ether (PBDE)-153, and polychlorinated biphenyl (PCB)-153
      on Daphnia magna. According to the 24-h acute toxicity test, up to concentration
      of 210 microg/L, these chemicals were not toxic to Daphnia. In the reproductive
      tests, we used concentrations of 12.5, 25, 50, and 100 microg/L. At the
      concentrations of 50 and 100 microg/L, the Daphnia started to die after the
      second test day, and there were no Daphnia alive on the fourth test day. The
      testing was continued using the concentrations of 12.5 and 25 microg/L. The
      reproductive tests were then repeated using only concentrations of 12.5 and 25
      microg/L. The results, based on the weight per volume (w/v) concentrations,
      showed that of the three compounds we tested PCB-153 had the most severe effects
      on the Daphnia reproduction. PBDE-153 was the least toxic, although in this
      group, too, offspring production was significantly lower and mortality
      significantly higher than those in the control group. Also, it was observed that
      PCB-153 accumulated into the parent Daphnia nearly three times more actively than
      the two other chemicals we tested. These chemicals, although having very similar
      structures, seem to affect differently the reproduction of Daphnia. They also
      seem to accumulate differently into Daphnia. Thus, further research data are
      needed to understand the mechanisms responsible for the effects caused by these
      kinds of chemicals and to assess their risks accurately.

PMID- 18082265
TI  - Potential of vetiver (Vetiveria zizanoides L. Nash) for phytoremediation of
      phenol.
AB  - Aseptically grown Vetiveria zizanoides were evaluated for their potential for
      phytoremediation of phenol from Murashige and Skoog's liquid medium. Phenol was
      found to be completely removed from incubation medium at the end of 4 days by V.
      zizanoides plantlets, when medium was supplemented with 50 and 100 mg L(-1)
      phenol, while with 200, 500, and 1000 mg L(-1) of phenol, 89%, 76% and 70%,
      respectively, were removed. Phenol removal was found to be associated with
      inherent production of peroxidase and hydrogen peroxide. Coupled with H(2)O(2)
      formation, the levels of antioxidant enzymes like superoxide dismutase and
      peroxidase showed an enhancement when plants were exposed to phenol, whereas
      catalase levels initially showed a decline due to the utilization of H(2)O(2) by
      peroxidase for phenol oxidation. However, when peroxidase levels declined, there
      was an enhancement in catalase levels to minimize the presence of H(2)O(2) in the
      medium. Having confirmed that the removal of phenol was by V. zizanoides
      plantlets, in the next phase, micropropagated plantlets and well-developed plants
      grown in hydroponics were used under in vivo conditions to study the effect of
      phenol (200 mg L(-1)) on plant growth and reuse. Although plant growth was
      reduced in presence of phenol, the results of the reuse study indicated the
      possibility of plants getting adapted to phenol without any decline in potential
      for phenol remediation.

PMID- 18082266
TI  - Toxic effects of 1-methyl-3-octylimidazolium bromide on the early embryonic
      development of the frog Rana nigromaculata.
AB  - Toxic effects of 1-methyl-3-octylimidazolium bromide ([C8mim]Br) on the early
      embryonic development of the frog Rana nigromaculata were evaluated. Frog embryos
      in different developmental stages (early cleavage, early gastrula, or neural
      plate) were exposed to 0, 45, 63, or 88.2 mg/L of the ionic liquid [C8mim]Br for
      96 h. The 96-h median lethal concentration values at the early cleavage, early
      gastrula, and neural plate stages of development were 85.1, 43.4, and 42.4 mg/L,
      respectively. In embryos exposed to [C8mim]Br, the duration of embryo
      dechorionation was prolonged in the early cleavage and neural plate, but not the
      early gastrula, stages of development compared with control embryos. Embryos in
      the neural plate developmental stage were found to have the highest mortality
      rate following [C8mim]Br exposure. These results suggest that [C8mim]Br has toxic
      effects on the early embryonic development of the frog.

PMID- 18082267
TI  - The elucidation of KIR2DL4 gene polymorphism.
AB  - The killer cell immunoglobulin-like receptors (KIRs) on NK cells recognize
      defined groups of HLA class I alleles. By this mechanism the NK cells fulfil a
      significant role in the first line of defense against infectious agents and
      cancer. For the treatment of leukaemia this NK cell allorecognition is of great
      importance. Still, an appropriate effect against the leukaemic cells requires
      sufficient expression of both KIR and HLA proteins. KIR gene polymorphism
      influence membrane expression of the KIR protein. We addressed KIR2DL4 gene
      polymorphism by a newly developed DNA and cDNA based direct sequencing based
      typing (SBT) and cloning approach. A panel of 44 individuals revealed a variety
      of KIR2DL4 alleles. Three new alleles have been identified, among those one
      allele showed alternatively spliced products. In conclusion, this approach is
      applicable for routine KIR2DL4 allele typing and enables the characterisation of
      new KIR2DL4 alleles.

PMID- 18082268
TI  - Studies on the anti-proliferative effects of novel DNA-intercalating bipyridyl
      thiourea-Pt(II) complexes against cisplatin-sensitive and -resistant human
      ovarian cancer cells.
AB  - Six bipyridyl complexes of platinum(II) with thiourea, with different
      substituents on thiourea moiety [Pt(bipy)(R,R'NCSNR'',R''')(2)]Cl(2) (bipy=2,2'
      bipyridine: R=R'=R''=R''' =H; R=Me, R'=R''=R'''=H; R=n-Bu, R'=R''=R'''=H; R=Et,
      R'=H, R''=Et, R'''=H; R=p-tolyl, R'=R''=R'''=H; R=phenyl, R'=H, R''=phenyl,
      R'''=H), rationally designed to intercalate into DNA, have been tested against a
      cisplatin (cDDP)-sensitive human ovarian carcinoma cell line (2008) and its 
      resistant variant (C13( *)). We show here that the anti-proliferative efficacy of
      these drugs was dependent on molecular structure, since it increased with
      ancillary ligand bulkiness and hydrophobicity of substituents on thiourea moiety.
      In particular, the presence of two phenyl groups on thiourea moiety confers an
      outstanding cytotoxicity. The increasing cell growth inhibition along the series
      of complexes partially paralleled with drug accumulation, particularly in
      resistant cells, but not with drug intercalation into DNA since all compounds
      exerted comparable ethidium bromide displacement ability. The cDDP-resistant
      phenotype seems, at least in part, to be involved in the action of these
      compounds, since the level of cross-resistance established for most complexes
      appeared to be in agreement with the observed impairment of drug accumulation in
      the resistant subline. These findings indicate that resistance to alkylating
      agents such as cDDP confers low level of cross-resistance to this class of DNA
      intercalators, which, however, depending on substituents on thiourea moiety may
      present remarkable cell growth inhibition even of resistant cells.

PMID- 18082269
TI  - Increasing incidence of Candida parapsilosis candidemia with caspofungin usage.
AB  - OBJECTIVES: To determine the impact on the change in epidemiology of Candida
      species at our institution since the introduction of caspofungin. METHODS: A 5
      year retrospective review of all candidemia at a major tertiary care center. Only
      one episode of candidemia per patient per admission was counted. All antifungal
      defined daily doses were also collected in this same time period. Regression
      analysis was performed on the data and correlation statistics among antifungal
      use and Candida species were assessed using a Pearson correlation analysis.
      RESULTS: There were 469 individual episodes of candidemia between fiscal year
      2002 and 2006 with the rate increasing every year. On regression analysis there
      was a significant increase in Candida parapsilosis candidemia (R(2)=0.90, p=0.02)
      and significant increase in caspofungin usage (R(2)=0.80, p<0.01), with a
      correspondingly significant decline in conventional (R(2)=-0.77, p<0.01) and
      lipid amphotericin B (R(2)=-0.95, p<0.05) usage. We found correlations between
      increased caspofungin usage (R(2)=0.94, p=0.017) and increased C. parapsilosis
      candidemia and decreased Candida tropicalis candidemia (R(2)=0.92, p<0.05) and a
      trend towards decreased Candida glabrata (R(2)=0.64, p=0.1). CONCLUSIONS: We
      showed significant correlations between increased caspofungin usage and an
      increased incidence of C. parapsilosis candidemia and reduction in C. tropicalis
      candidemia, with a trend towards less C. glabrata candidemia.

PMID- 18082270
TI  - Reduced incidence of insect-bite hypersensitivity in Icelandic horses is
      associated with a down-regulation of interleukin-4 by interleukin-10 and
      transforming growth factor-beta1.
AB  - Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by
      IgE-mediated reactions to bites of insects of the genus Culicoides. IBH does not
      occur in Iceland due to the absence of Culicoides. However, Icelandic horses
      exported to mainland Europe as adults (1st generation) have a > or =50% incidence
      of developing IBH. In contrast, their progeny (2nd generation) has a <10%
      incidence of IBH. Here we show that peripheral blood mononuclear cells (PBMC)
      from Icelandic horses born in mainland Europe and belonging either to the IBH or
      healthy subgroup produce less interleukin (IL)-4 after polyclonal or allergen
      specific stimulation when compared with counterparts from horses born in Iceland.
      We examined a role of IL-10 and transforming growth factor (TGF)-beta1 in down
      regulation of IL-4 in healthy 2nd generation Icelandic horses. Supernatants of
      PBMC from 2nd generation healthy horses down-regulated the proportion of IL-4
      producing cells and IL-4 production in stimulated cultures of PBMC from 1st
      generation IBH. This inhibition was mimicked by a combination of IL-10 and TGF
      beta1 but not by the single cytokines. Cultures of stimulated PBMC of healthy 2nd
      generation horses produced a low level of IL-4, but IL-4 production was increased
      by anti-equine IL-10 and anti-human TGF-beta1. This shows for the first time that
      in horses, IL-10 and TGF-beta1 combined regulate IL-4 production in vitro. It is
      suggested that in this naturally occurring IgE-mediated allergy, IL-10 and TGF
      beta1 have a role in the down-regulation of IL-4-induced allergen-specific Th2
      cells, thereby reducing the incidence of IBH.

PMID- 18082271
TI  - The role of tryptophan metabolism in iNOS transcription and nitric oxide
      production by chicken macrophage cells upon treatment with interferon gamma.
AB  - The influence of de novo synthesis of nicotinamide adenine dinucleotide (NAD)
      through the kynurenine (KYN) pathway of tryptophan (TRP) degradation on gene
      transcription of inducible nitric oxide synthase (iNOS) and nitric oxide (NO)
      production in chicken interferon gamma (ChIFN-gamma)-stimulated and non
      stimulated chicken macrophage cell line HD11 was investigated. Interferon gamma
      up regulation of iNOS transcription and NO production was dependent on an
      undisturbed flow through the KYN pathway. Inhibition of indoleamine-2,3
      dioxygenase, the rate-limiting enzyme of TRP catabolism, by 1-methyl-l-tryptophan
      (1-mTRP) down regulated both iNOS gene transcription and NO production. Addition
      of KYN to 1-mTRP-treated, ChIFN-gamma-stimulated macrophages circumvented the
      down regulation of iNOS transcription and NO production. Inhibition of poly(ADP
      ribose) polymerase (PARP), a nuclear enzyme involved in DNA repair, replication
      and transcription, which cleaves NAD into nicotinamide and ADP-ribose, down
      regulated iNOS gene transcription and NO production in ChIFN-gamma-stimulated
      HD11 cells. Our results suggest that prevention of NAD depletion in HD11 cells by
      ChIFN-gamma-mediated induction of IDO facilitates iNOS transcription and NO
      production. This effect is most likely a result of PARP1 automodification in the
      presence of NAD, known to facilitate transcription by changing chromatin
      structure and to allow NFkappaB binding to iNOS promoter which is hindered by
      direct protein-protein interaction between NFkappaB and unmodified PARP1.

PMID- 18082272
TI  - Role of IFN-gamma responsiveness in CD8 T-cell-mediated viral clearance and
      demyelination in coronavirus-infected mice.
AB  - Immunocompetent, but not RAG1(-/-) mice infected with MHV-JHM develop
      demyelination. Transferred CD8 T cell-enriched splenocytes reconstitute
      demyelination, and this ability is dependent on donor IFN-gamma. We used IFN
      gammaR1(-/-) mice to examine the target of IFN-gamma in CD8 T cell-mediated
      demyelination. In IFN-gammaR1(-/-)RAG1(-/-) recipients, demyelination is
      decreased, but not eliminated, while viral titers are significantly increased
      when compared to IFN-gammaR1(+/+)RAG1(-/-) recipients. IFN-gammaR1(-/-) CD8 T
      cells retain virus-specific effector function regardless of IFN-gammaR1
      expression. Although IFN-gammaR1 responsiveness is critical for maximal
      demyelination, increased levels of infectious virus coupled with adoptive
      transfer of CD8 T cells may result in myelin destruction independent of IFN
      gammaR1 expression.

PMID- 18082273
TI  - Maxillary sinus melanoma as the presenting feature of Carney complex.
AB  - We present a case of a large maxillary sinus tumor in a 6-year-old boy,
      immunohistologically indistinguishable from a malignant melanoma, that led to the
      diagnosis of Carney complex. The Carney complex is an autosomal dominant disorder
      characterized by mucocutaneous pigmented lesions and neoplasia of multiple
      endocrine glands and is usually due to an inactivating mutation of the gene for
      the protein kinase A regulatory subunit 1A. The Carney complex has characteristic
      head and neck manifestations that can point to the diagnosis of this potentially
      lethal condition.

PMID- 18082274
TI  - Development of a quantitative real-time PCR for determination of genotype
      frequencies for studies in baculovirus population biology.
AB  - Two bacmid-derived Autographa californica Multiple-capsid Nucleopolyhedrovirus
      genotypes - that differ only in a short tag sequence for differential PCR
      recognition - were generated. By electron microscopy, these genotypes were found
      to have identical polyhedra morphology. Mixtures of quantified polyhedra were
      made and used to validate a SYBR Green I-based quantitative real-time PCR (qPCR)
      to determine genotype frequencies in mixed genotype populations. The PCR could
      accurately quantify genotype ratios over a range of 8 orders of magnitude. Only a
      small correction of the genotype ratio was necessary to obtain a valid result.
      Low levels of aspecific background (a fluorescent signal when the template
      corresponding with the primer set used is not present) were measured in these
      validation experiments and in a typical laboratory setup. A small fitness
      difference between the genotypes generated was observed in a median lethal dose
      bioassay. The bacmid-derived virus genotypes generated and the qPCR assays are
      valuable tools for studying the population biology of baculoviruses.

PMID- 18082275
TI  - Repeated intracerebral teneurin C-terminal associated peptide (TCAP)-1 injections
      produce enduring changes in behavioral responses to corticotropin-releasing
      factor (CRF) in rat models of anxiety.
AB  - The teneurin C-terminal associated peptides (TCAP) are a recently discovered
      family of peptides encoded by a bioactive neuropeptide-like gene sequence found
      at the carboxy terminus of the teneurin transmembrane proteins. TCAP is
      structurally related to the corticotropin-releasing factor (CRF) family of
      peptides. Synthetic TCAP-3 and TCAP-1 are active in vitro in stimulating cAMP and
      proliferation in neuronal lines. TCAP-1 mRNA is expressed in limbic brain regions
      and modulates acoustic startle behavior in rats when injected into the
      basolateral amygdala. In the current study, TCAP-1 was administered into the
      cerebral ventricles once per day for 5 days to rats. At 1-3 weeks after the last
      TCAP-1 treatment, the rats were tested in the elevated plus maze, open field
      test, or the acoustic startle test, with or without an acute CRF injection 30 min
      prior to the test. The results show a difference in behavioral response between
      TCAP-treated and saline-treated rats, but only when an acute CRF challenge is
      delivered prior to testing. In the plus maze and open field tests, acute CRF
      effects were enhanced by prior TCAP-1 treatment, whereas in the acoustic startle
      test, the acute CRF effects were diminished by prior TCAP-1 administration.

PMID- 18082276
TI  - Comparison of the effect of an H(3)-inverse agonist on energy intake and
      hypothalamic histamine release in normal mice and leptin resistant mice with high
      fat diet-induced obesity.
AB  - Leptin is a key signal linking peripheral adiposity levels to the regulation of
      energy homeostasis in the brain. The injection of leptin decreases body weight
      and food intake in lean rodents; however, in a rodent model of high fat diet
      induced obesity (DIO), the exogenous leptin cannot improve adiposity. This
      ineffectiveness is known as leptin resistance, and the factors downstream of
      leptin signaling have received attention as viable targets in the treatment of
      obesity. We previously reported that the histaminergic system is one of the
      targets of leptin. In the present study, the effect of an H(3)-receptor inverse
      agonist on hypothalamic histamine release and energy intake was investigated in
      normal and DIO mice. Leptin (1.3 mg/kg, i.p.) significantly increased
      hypothalamic histamine release and reduced 12 h-energy intake in normal mice, but
      had no such effects in DIO mice. In contrast, clobenpropit (5 mg/kg, i.p.), an
      H(3)-inverse agonist, elicited a significant increase in histamine release in
      both types of mice. Clobenpropit did not reduce 12 h-energy intake; however, it
      decreased 3 h-energy intake in both types of mice. These results suggest that
      lack of the activation of the histaminergic system partly contributes to obesity
      in DIO mice and direct activation of the histaminergic system circumvents leptin
      resistance.

PMID- 18082277
TI  - Cadmium biodynamics in the oligochaete Lumbriculus variegatus and its
      implications for trophic transfer.
AB  - It has become increasingly apparent that diet can be a major source of trace
      metal bioaccumulation in aquatic organisms. In this study, we examined cadmium
      uptake, efflux, and subcellular compartmentalization dynamics in the freshwater
      oligochaete Lumbriculus variegatus. L. variegatus is an important component of
      freshwater food webs in Europe and North America and is potentially useful as a
      standard food source for laboratory-based trophic transfer studies. Cadmium
      accumulation and depuration were each followed for 10 days. Rate constants of
      uptake (k(u)) and efflux (k(e)) were estimated and subcellular Cd
      compartmentalization was followed over the course of uptake and efflux. The
      partitioning of Cd into operationally-defined subcellular compartments was
      relatively consistent throughout the 20-day experiment, with the majority of Cd
      accumulating in the cytosol. No major changes in Cd compartmentalization were
      observed over uptake or depuration, but there appeared to be some exchange
      between heat-stable and heat-labile cytosolic protein fractions. Cadmium
      accumulation from solution was strongly affected by ambient calcium
      concentrations, suggesting competition between Cd and Ca for uptake sites.
      Finally, we demonstrate the ability to manipulate the whole body calcium content
      of L. variegatus as a potential tool for examining calcium influences on dietary
      Cd dynamics. The potential for this species to be an important conduit of Cd to
      higher trophic levels is discussed, along with its potential as a standardized
      food source in metal trophic transfer studies.

PMID- 18082278
TI  - Ketoconazole, an antifungal imidazole, increases the sensitivity of rainbow trout
      to 17alpha-ethynylestradiol exposure.
AB  - This study focuses on effects of two classes of xenobiotics, azole fungicides and
      xenoestrogens, both of which have been detected in the aquatic environment. We
      hypothesize that azoles and estrogenic compounds are metabolized by cytochrome
      P450 (CYP) enzymes, and in particular CYP1A and CYP3A, to more readily excreted
      metabolites. We exposed rainbow trout (Oncorhynchus mykiss) to two different
      pharmaceutical representatives of theses two classes, such as the imidazole
      ketoconazole and the synthetic estrogen analogue, 17alpha-ethynylestradiol
      (EE(2)). Juvenile rainbow trout were i.p. injected with a single low dose of
      EE(2) (2.5 microg/kg), alone or in combination with ketoconazole (100mg/kg).
      Hepatic microsomal CYP1A and CYP3A protein expressions were analyzed in Western
      blots using polyclonal antibodies (PAb) and enhanced cheminoluminescence. CYP1A
      activities were analyzed using the ethoxyresorufin-O-deethylase (EROD) assay and
      CYP3A activities were analyzed using the benzyloxy-4-[trifluoromethyl]-coumarin-O
      debenzyloxylase (BFCOD) assay. Plasma vitellogenin (vtg) and sex steroid hormones
      (i.e. 17beta-estradiol, testosterone and 11-keto-testosterone) were analyzed
      using commercially available ELISA-kits. The vtg mRNA expression was analyzed
      using quantitative (Q)-PCR. The dose of EE(2) selected had little or no effect on
      the estrogen receptor (ER) mediated vtg induction. However, in combination with
      ketoconazole this threshold-dose of EE(2) resulted in significantly elevated
      plasma vtg levels, 6 days post injection. Exposure to ketoconazole resulted in up
      to nine-fold induction of CYP1A after 3 days. However, this nine-fold induction
      was not reflected on the CYP1A catalytic activity, where exposure to ketoconazole
      resulted only in a two-fold increase in activity. Ketoconazole increased CYP3A
      protein levels 1.5-fold and decreased BFCOD activities by 80% at days 3 and 6.
      Treatment with ketoconazole and EE(2) alone and in combination had no significant
      effect on sex steroid hormones, compared to vehicle-treated fish. This study
      demonstrates that exposure to ketoconazole compromises the function of key
      enzymes involved in metabolic clearance of xenobiotics and steroids, and
      increases the sensitivity to EE(2) exposure in juvenile rainbow trout.

PMID- 18082279
TI  - Rapidly growing angiosarcoma of the pericardium presenting as hemorrhagic
      pericardial effusion.
AB  - Primary angiosarcoma of the heart is exceptionally rare. Angiosarcoma of the
      heart often go undetected until late in the course of the disease as symptoms are
      insidious and available non-invasive imaging modalities lack specificity.
      Recently, we experienced an angiosarcoma of the pericardium that presented
      hemorrhagic pericardial effusion initially, but progressed rapidly during short
      period. Our case showed that, when initial diagnosis is not clear, early
      aggressive diagnostic modality such as surgical exploration or more frequent
      follow-up examination is needed for earlier detection and chance of targeted
      therapy. Of particular, unexplained bloody pericardial effusion as observed in
      our patient should prompt the clinician to continue to search for a malignant
      etiology for improving survival in this fatal cancer.

PMID- 18082280
TI  - Different perceptual sensitivities for Chernoff's face between children and
      adults.
AB  - The aim of this study was to investigate the differences between children and
      adults in recognizing facial expressions of simple line drawings of "Chernoff's
      face". First, the angles of the eyebrows and mouth of Chernoff's face were
      changed in a stepwise way with a personal computer, and the emotional response of
      the subjects was evaluated by a questionnaire. Second, three drawings of non
      target stimuli (neutral face, angry face, and wheelchair) and target stimuli were
      used to elicit event-related potentials (ERPs). Children had higher scores for
      the facial expressions than adults, and relied much more on the angles of the
      eyebrows and mouth. The major ERP findings were (1) the latencies of P100 and
      N170 were significantly longer in children than adults, (2) the amplitudes of
      P100 were significantly larger in children than adults, but the N170 amplitudes
      were not significantly different, and (3) a slow negative shift was recorded with
      a latency of 240-460ms at the posterior-temporal site for angry face compared
      with neutral face in adults but not in children. These results suggest that the
      differences in the electrophysiological recognition of facial expressions can be
      set at 240ms after appearance of the Chernoff's face in adults but not in
      children.

PMID- 18082281
TI  - The oral absorption of phospholipid prodrugs: in vivo and in vitro mechanistic
      investigation of trafficking of a lecithin-valproic acid conjugate following oral
      administration.
AB  - The purpose of this study was to evaluate the oral absorption characteristics of
      a phospholipid-drug conjugate, comprising direct conjugation between the lecithin
      and the drug moiety through the sn-2 position. We investigated the mechanisms
      involved with the trafficking of this conjugate following oral administration in
      the gastrointestinal (GI) lumen, within the enterocyte and further. A
      phospholipid-valproic acid conjugate (DP-VPA) was utilized as a model molecule.
      The oral absorption of this conjugate in rats was investigated following
      administration in long (LCT) vs. medium (MCT) chain triglyceride formulations,
      and in the postprandial vs. fasted state. Oral administration within the LCT
      solution caused more than a 3-fold increase in DP-VPA bioavailability in
      comparison to the MCT solution. Moreover, a significant food effect was evident
      for DP-VPA. Hence, we evaluated the lymphatic transport of DP-VPA in mesenteric
      lymph duct cannulated freely moving rats. Sixty percent of the absorbed DP-VPA
      was associated with lymphatic transport. Similar DP-VPA absorption was obtained
      in secretory type II PLA(2) knockout mice (C57BL/6) and in control mice (BALB/c).
      Moreover, nil DP-VPA degradation in serum and very low (4.8%) degradation by bee
      venom PLA(2)in vitro were obtained. In conclusion, direct conjugation between the
      drug and the phospholipid produces a complex having unique absorption properties
      that include: (1) a stable complex that does not undergo degradation in the GI
      tract; (2) permeation through the gut wall and entering intact to the enterocyte;
      and (3) association with chylomicron in the enterocyte and reaching the systemic
      circulation via the lymphatic route. These unique properties may be of interest
      in drug delivery.

PMID- 18082282
TI  - Improved intestinal absorption of calcitonin by mucoadhesive delivery of novel
      pectin-liposome nanocomplexes.
AB  - Self-assembling pectin-liposome nanocomplexes (PLNs) were prepared by a simple
      mixing of cationic liposomes with pectin solution, in order to improve intestinal
      absorption of calcitonin (eCT). Both in-vitro and in-vivo evaluations for PLNs
      were evaluated. The results showed that average particle size of PLNs was
      significantly larger than that of initial cationic liposomes. The surface charges
      were shifted from positive to negative after mixing with pectin. The PLNs made of
      high degree of esterification (DE) pectin showed less negatively charged values
      than those made of low DE pectin. The entrapment efficiency in cationic liposomes
      was in the same range even if the drug loading was increased. The in-vivo
      mucoadhesive test of pectin by confocal laser scanning microscopy demonstrated
      stronger mucoadhesive properties of PLNs made of low DE pectin, compared to
      cationic liposomes and PLNs made of other pectins. Moreover, high intensities of
      a fluorescent marker could be observed throughout the small intestines (i.e.
      duodenum, jejunum and ileum) and remained at the site of mucoadhesion even after
      6 h of administration of PLNs made of low DE pectin. The eCT-loaded PLNs
      demonstrated a strong pharmacological action over the eCT solution and eCT-loaded
      liposomes, in which an enhanced and prolonged reduction in plasma calcium
      concentration of rats was observed. This was attributed to the ability of pectin
      to adhere to the mucus layer and prolong retention in the intestinal mucosa.

PMID- 18082283
TI  - Organogels and their use in drug delivery--a review.
AB  - Organogels are semi-solid systems, in which an organic liquid phase is
      immobilized by a three-dimensional network composed of self-assembled,
      intertwined gelator fibers. Despite their majoritarily liquid composition, these
      systems demonstrate the appearance and rheological behaviour of solids.
      Investigative research pertaining to these systems has only picked up speed in
      the last few decades. Consequently, many burning questions regarding organogel
      systems, such as the specific molecular requirements guaranteeing gelation, still
      await definite answers. Nonetheless, the application of different organogel
      systems to various areas of interest has been quick to follow their discoveries.
      Unfortunately, their use in drug delivery is still quite limited by the scarce
      toxicology information available on organogelators, as well as by the few
      pharmaceutically-accepted solvents used in gel systems. This review aims at
      providing a global view of organogels, with special emphasis on the interplay
      between the gelator's structural characteristics and the ensuing intermolecular
      interactions. A subsequent focus is placed on the application of organogels as
      drug delivery platforms for active agent administration via diverse routes such
      as transdermal, oral, and parenteral.

PMID- 18082284
TI  - Short-term reproducibility of impaired fasting glycaemia, impaired glucose
      tolerance and diabetes The ADDITION study, DK.
AB  - We evaluated variations in glucose measurements and the reproducibility of
      glucose tolerance classification in a high-risk screening setting in general
      practice. Screening for diabetes was performed in persons aged 40-69 years. Based
      on capillary fasting (FBG) and 2-h blood glucose (2 hBG) individuals with
      impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT) and diabetes
      had a second test done after 14 days. Intra-individual coefficients of variation
      (CV) were estimated in each glucose tolerance class using the approximation
      CV(2)(x)=var(ln(x)). Bland-Altman plots with limits of agreement were made. In
      the total population, the CV(intra) was 7.9% and 13.8% for FBG and 2 hBG,
      respectively. Limits of agreement ranged from -1.15 to 1.67 mmol/l for FBG and
      from - 2.62 to 3.27 mmol/l for 2 hBG. One individual with IFG and 22.5% with IGT
      had diabetes at the second test, 76.1% with diabetes had this diagnosis
      confirmed, and about 30% with IFG and IGT had normal glucose tolerance at the
      second test. The expected values of repeated capillary blood glucose measurements
      were about+/-1 and+/-3 mmol/l for FBG and 2 hBG, respectively. Yet, 70% of high
      risk prediabetic individuals were persistently classified with abnormal glucose
      regulation; diabetes was confirmed in 76% of the cases.

PMID- 18082285
TI  - A simple clinical score for type 2 diabetes mellitus screening in the Canary
      Islands.
AB  - AIM: To develop a straightforward risk score for type 2 diabetes (DM2) screening
      to use in clinical practice. METHODS: A sample of 6237 adult inhabitants of the
      Canary Islands (Spain) was randomly divided into two subgroups: one yielded data
      used to develop the instrument, and the other yielded data used for validation
      testing. Performance of the instrument was compared in persons with clinically
      diagnosed DM2 and undiagnosed diabetes. The risk score, calculated by
      multivariate logistic regression, included the potential risk variables that
      yielded the highest odds ratio in the univariate analysis. A cut-off point for
      screening purposes was established at a 99% negative predictive value. RESULTS:
      In men, variables included in the risk score were age, waist/height ratio,
      familial antecedents of diabetes, and systolic blood pressure (ROC curve 0.837,
      95% CI: 0.803-0.871). In women, the risk score contained the same variables plus
      gestational diabetes history (ROC curve 0.874, 95% CI: 0.847-0901). Excluding
      systolic blood pressure from the score had no significant effect on the area
      under the curve. This instrument resulted valid only for people aged less than 55
      years. CONCLUSIONS: This simple risk score for DM2 would be easy to apply in
      clinical practice.

PMID- 18082286
TI  - Perceived smoking prevalence at school-level and children's smoking initiation: a
      multi-level analysis of a cross-sectional data in Taiwan.
AB  - OBJECTIVES: Literature on the influence of smoking prevalence at school-level on
      the smoking initiation among elementary school children is scarce. The aim of the
      current study was to explore this in school clusters stratified according to
      student's perceived smoking prevalence in the school while adjusting for social
      impact of individual students. METHOD: The data was obtained from a survey
      administered to 13 elementary schools in Taoyuan County, a final sample of 1585
      3rd and 4th grade students. Multi-level logistic regression analysis (MLRA) was
      used to examine the influence variable at school-level as well as individual
      socio-environment level had on smoking status of elementary schools students.
      RESULTS: Attending a school where the students reported a perception of high
      smoking prevalence had a greater effect on smoking behavior in boys than girls
      when compared with students attending a lower smoking prevalence school, after
      adjustment for student-level characteristics. CONCLUSIONS: Our study confirmed
      that a broader school environment with a high student perception of smoking
      prevalence is associated with children's smoking behavior in boys. The findings
      further indicate the need for enforcement of anti-smoking policies within schools
      with higher smoking rates to reduce visibility of smoking among school children.

PMID- 18082287
TI  - [Orn5]URP acts as a pure antagonist of urotensinergic receptors in rat cortical
      astrocytes.
AB  - Cultured rat astrocytes, which express functional urotensin II (UII)/UII-related
      peptide (URP) receptors (UT), represent a very suitable model to investigate the
      pharmacological profile of UII and URP analogs towards native UT. We have
      recently designed three URP analogs [D-Trp4]URP, [Orn5]URP and [D-Tyr6]URP, that
      act as UT antagonists in the rat aortic ring bioassay. However, it has been
      previously reported that UII/URP analogs capable of inhibiting the contractile
      activity of UII possess agonistic activity on UT-transfected cells. In the
      present study, we have compared the ability of URP analogs to compete for [125
      I]URP binding and to modulate cytosolic calcium concentration ([Ca2+]c) in
      cultured rat astrocytes. All three analogs displaced radioligand binding: [D
      Trp4]URP and [D-Tyr6]URP interacted with high- and low-affinity sites whereas
      [Orn5]URP only bound high-affinity sites. [D-Trp4]URP and [D-Tyr6]URP both
      induced a robust increase in [Ca2+]c in astrocytes while [Orn5]URP was totally
      devoid of activity. [Orn5]URP provoked a concentration-dependent inhibition of
      URP- and UII-evoked [Ca2+]c increase and a rightward shift of the URP and UII
      dose-response curves. The present data indicate that [D-Trp4]URP and [D-Tyr6]URP,
      which act as UII antagonists in the rat aortic ring assay, behave as agonists in
      the [Ca2+]c mobilization assay in cultured astrocytes, whereas [Orn5]URP is a
      pure selective antagonist in both rat aortic ring contraction and astrocyte
      [Ca2+]c mobilization assays.

PMID- 18082289
TI  - Over-expressed human divalent metal transporter 1 is involved in iron
      accumulation in MES23.5 cells.
AB  - Elevated iron accumulation has been reported in brain regions in some
      neurodegenerative disorders. However, the mechanism for this is largely unknown.
      Divalent metal transporter 1 (DMT1) is an important divalent cation transporter.
      The aim of the present study is to construct recombinant adenovirus encoding
      human DMT1 with iron responsive element (DMT1+IRE) and infect MES23.5
      dopaminergic cells in order to investigate the relationship between increased
      DMT1+IRE expression and iron accumulation. The human DMT1 gene was obtained by RT
      PCR from tissues of human duodenum. AdDMT1+IRE was successfully constructed and
      identified by PCR, restriction endonuclease analyses and DNA sequencing,
      respectively. It was able to efficiently infect MES23.5 cells, which was
      confirmed by RT-PCR and Western blots. When incubated with 100 microM ferrous
      iron for 6h, the intracellular iron levels dramatically increased in AdDMT1+IRE
      infected MES23.5 cells compared to the solely adenovirus infected cells.
      Meanwhile, the levels of hydroxyl free radicals and malondialdehyde (MDA) in
      these cells increased. This led to the activation of caspase-3. The apoptosis in
      AdDMT1+IRE infected cells was shown with hypercondensed nuclei using Hoechst
      staining. Analysis of DNA extracted from these cells showed the typical "ladder
      pattern", indicating the formation of mono- and oligonucleosomes. These results
      suggested that increased DMT1+IRE expression in MES23.5 cells caused the
      increased intracellular iron accumulation. This resulted in the increased
      oxidative stress leading to ultimate cell apoptosis.

PMID- 18082288
TI  - PYY(3-36) induces Fos in the arcuate nucleus and in both catecholaminergic and
      non-catecholaminergic neurons in the nucleus tractus solitarius of rats.
AB  - Peptide YY (3-36) [PYY(3-36)] inhibits feeding in rodents, nonhuman primates and
      humans, yet the neural circuits underlying this action remain to be determined.
      Here we assessed whether PYY(3-36) inhibits feeding by activating neurons in
      forebrain and hindbrain sites containing Y2 receptors and linked to control of
      food intake, or in hindbrain sites immediately downstream of vagal afferent
      neurons. Rats received an anorexigenic dose of PYY(3-36), and the number of
      neurons expressing Fos, an indicator of neuronal activation, was determined in
      anterior hypothalamus (AH), arcuate nucleus (ARC), dorsomedial hypothalamus
      (DMH), lateral hypothalamus (LH), ventromedial hypothalamus (VMH), central
      nucleus of the amygdala (CeA), area postrema (AP), and caudal medial nucleus
      tractus solitarius (cmNTS), commissural NTS (cNTS), and gelatinosus NTS (gNTS).
      Expression of tyrosine hydroxylase (TH), an indicator of catecholamine synthesis,
      was also measured in the cmNTS. PYY(3-36) increased Fos in ARC, cmNTS, gNTS and
      AP. Approximately 10% of Fos+ neurons in the cmNTS were TH+. These results
      suggest that PYY(3-36) inhibits feeding through direct activation of ARC neurons,
      and direct and/or indirect activation via vagal afferent nerves of cmNTS, gNTS
      and AP, including some catecholaminergic neurons in the cmNTS.

PMID- 18082290
TI  - CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as
      an application example.
AB  - Phosphodiesterase (PDE) 7 is a high affinity cAMP-specific PDE whose functional
      role in T-cells has been the subject of some controversy. Recent findings on
      tissue distribution, however, support the hypothesis that PDE7 could be a good
      target for the treatment of airway diseases, T-cell related diseases or central
      nervous system (CNS) disorders. Therefore, the identification of selective
      inhibitors targeted against PDE7 enzyme has become an attractive area of
      research. We report here the first use of the descriptors generated by the CODES
      program for ligand-based virtual screening. This program codifies molecules from
      a topological point of view and the generated descriptors are related to the
      chemical nature of the atoms, the atomic bonds and the connectivity with the rest
      of the molecule. They are also able to distinguish among stereoisomers. By using
      this approach, 173 compounds were codified, and their similarity with the
      reference compound was analysed. Based on the analysis, new potential PDE7
      inhibitors have been identified, synthesized and biologically evaluated
      confirming that CODES descriptors are valid for ligand-based virtual screening
      and provided new lead compounds for further optimization as potent and selective
      PDE7 inhibitors.

PMID- 18082291
TI  - Dietary intake adequacy and cognitive function in free-living active elderly: a
      cross-sectional and short-term prospective study.
AB  - BACKGROUND & AIMS: Adequate dietary intake might prevent cognitive decline among
      ageing subjects; hence, the relationships between dietary intake and cognitive
      function in a sample of non-institutionalized active elderly were assessed.
      METHODS: Total 187 subjects aged over 65. Dietary intake was assessed using a
      three-day record and cognitive function using the mini-mental state examination
      (MMSE). After 8.5+/-3.5 months of follow-up, cognitive function was re-assessed
      in 110 subjects. RESULTS: A considerable portion of the subjects presented a low
      intake of several key nutrients. At baseline, no differences were found between
      subjects with normal or low MMSE score regarding all dietary parameters. At
      follow-up, 63 subjects (57%) showed a mild improvement of their MMSE score; their
      consumption of calcium and of n-3 fatty acids was higher (p<0.01 and p<0.03,
      respectively) than subjects without improvement. Similarly, multivariate logistic
      regression showed subjects whose consumption of calcium was above the dietary
      reference intake had a significantly higher odds ratio (OR) of improving their
      MMSE (OR=5.41; 95% CI: 1.44-20.29), whereas no effect was found for n-3 fatty
      acids (OR=2.48; 95% CI: 0.46-13.36). CONCLUSION: Increased calcium consumption is
      related to improved cognitive function; the exact effect of n-3 fatty acids
      intake remains to be assessed.

PMID- 18082292
TI  - Re: typhoid fever vaccines: systematic review and meta-analysis of randomised
      clinical trials.

PMID- 18082293
TI  - Infection of monocytes or immature dendritic cells (DCs) with an attenuated
      rabies virus results in DC maturation and a strong activation of the NFkappaB
      signaling pathway.
AB  - To assess the potential role of dendritic cells (DCs) or monocytes in the
      development of a protective immune response, we infected human immature DCs or
      monocytes with a live rabies virus (RV) vaccine strain (SPBNGAS-GAS) and a
      pathogenic RV (DOG4). Both cell types were infected with SPBNGAS-GAS and DOG4 and
      both RVs were similarly potent in inducing maturation of immature DCs or
      monocytes. However, in contrast to DOG4, SPBNGAS-GAS induced very high levels of
      IFN-alpha1 mRNA in monocytes and DCs. Furthermore, at least 26 other genes
      related to the NFkappaB signaling pathway were strongly upregulated in SPBNGAS
      GAS-infected DCs, but only somewhat increased in DOG4-infected cells. Thus, the
      extent of upregulation of NFkappaB pathway-related genes in DCs infected with the
      live RV vaccine strain might explain the strong protective activity of SPBNGAS
      GAS.

PMID- 18082294
TI  - Intradermal/subcutaneous immunization by electroporation improves plasmid vaccine
      delivery and potency in pigs and rhesus macaques.
AB  - In an effort to improve DNA vaccine immune potency electroporation has emerged as
      a method of delivery of plasmids to target tissues. However, few studies have
      examined the use of this technology to deliver plasmid vaccines to the skin. Here
      we studied the effect of electroporation on DNA vaccine potency and gene delivery
      using skin as a target tissue in larger animal species. Using a pig model, we
      determined that high plasmid concentrations resulted in improved gene expression
      for plasmid GFP delivered by the intradermal/subcutaneous (ID/SQ) route. In a
      macaque model, we observed higher cellular and humoral responses to an HIV DNA
      vaccine, which included plasmid-encoded IL-12, with electroporation compared to
      ID/SQ injection alone. The induced responses were TH1 mediated. These results
      support that skin electroporation may have importance as an immunization approach
      in larger animal models.

PMID- 18082295
TI  - Immunogenicity and safety of aerosolized measles vaccine: systematic review and
      meta-analysis.
AB  - Aerosols are the most promising non-injectable method of measles vaccination
      studied so far and their efficacy is thought to be comparable to injected
      vaccine. We conducted a systematic review up to May 2006 to examine the
      immunogenicity and safety of aerosolized measles vaccine (Edmonston-Zagreb or
      Schwarz strains) 1 month or more after vaccination. Where possible we estimated
      pooled serological response rates and odds ratios (with 95% confidence intervals,
      CI) comparing aerosolized and subcutaneous vaccines in children in three age
      groups and adults. We included seven randomized trials, four non-randomized
      trials and six uncontrolled studies providing serological outcome data on 2887
      individuals. In children below 10 months, the studies were heterogeneous. In four
      comparative studies, seroconversion rates were lower with aerosolized than with
      subcutaneous vaccine and in two of these the difference was unlikely to be due to
      chance. In children 10-36 months, the pooled seroconversion rate with aerosolized
      vaccine was 93.5% (89.4-97.7%) and 97.1% (92.4-100%) with subcutaneous vaccine
      (odds ratio 0.27, 0.04-1.62). In 5-15-year olds the studies were heterogeneous.
      In all comparative studies aerosolized vaccine was more immunogenic than
      subcutaneous. Reported side effects were mild. Aerosolized measles vaccine
      appears to be equally or more immunogenic than subcutaneous vaccine in children
      aged 10 months and older. Large randomized trials are needed to establish the
      efficacy and safety of aerosolized measles vaccine as primary and booster doses.

PMID- 18082296
TI  - Sudden deaths following influenza vaccination: can this be expected?
AB  - BACKGROUND: In November 2006, four Dutch people, aged 53, 58, 80 and 88, died
      unexpectedly on the day they had received their influenza vaccination. A rapid
      epidemiological assessment was needed to quantify the risk of a causal
      association. METHODS: Using routinely available data on age-stratified population
      size, cardiovascular mortality, and vaccination coverage, a daily rate and daily
      risk of sudden death per 5-year age-group was calculated. A cumulative
      probability that at least one person in four specific age-groups would die on the
      day of vaccination was calculated using a binomial distribution. No assumptions
      on deaths in other age groups were included. RESULTS: The overall likelihood that
      at least one person in each of the four age categories 50-54, 55-59, 80-84 and 85
      89 would die suddenly on the day of influenza vaccination in the Netherlands was
      calculated to be 0.016. This was 330 times more likely than nobody dying in each
      of these categories, and 45 times less likely than the most probable outcome.
      CONCLUSION: We concluded that there was a small but real chance of the four
      deaths occurring without a causal link to the vaccination. Policy decisions
      regarding unexpected deaths following vaccination can benefit from a rapid
      epidemiological evaluation.

PMID- 18082297
TI  - Assessment of the natural radioactivity and radiological hazards in Turkish
      cement and its raw materials.
AB  - The natural radioactivity due to presence of (226)Ra, (232)Th and (40)K
      radionuclides in raw materials, intermediate products (clinker) and end products
      (22 different cement types) was measured using a gamma-ray spectrometry with HPGe
      detector. The specific radioactivity of (226)Ra, (232)Th and (40)K in the
      analyzed cement samples ranged from 12.5+/-0.3 to 162.5+/-1.7Bqkg(-1) with a mean
      of 40.5+/-26.7Bqkg(-1), 6.7+/-0.3 to 124.9+/-2.5Bqkg(-1) with a mean of 26.1+/
      18.9Bqkg(-1) and 64.4+/-2.3 to 679.3+/-18.2Bqkg(-1) with a mean of 267.1+/
      102.4Bqkg(-1), respectively. The radium equivalent activity (Ra(eq)), the gamma
      index, the emanation coefficient, the (222)Rn mass exhalation rate and the indoor
      absorbed dose rate were estimated for the radiation hazard of the natural
      radioactivity in all samples. The calculated Ra(eq) values of cement samples
      (37.2+/-8.7-331.1+/-15.5Bqkg(-1) with a mean of 98.3+/-53.8) are lower than the
      limit of 370Bqkg(-1) set for building materials. The Ra(eq) values were compared
      with the corresponding values for cement of different countries. The mean indoor
      absorbed dose rate is slightly higher than the population-weighted average of
      84nGyh(-1).

PMID- 18082298
TI  - Are there inequalities in choice of birthing position? Sociodemographic and
      labour factors associated with the supine position during the second stage of
      labour.
AB  - OBJECTIVE: to establish which factors are associated with birthing positions
      throughout the second stage of labour and at the time of birth. DESIGN:
      retrospective cohort study. SETTING: primary care midwifery practices in the
      Netherlands. PARTICIPANTS: 665 low-risk women who received midwife-led care.
      MEASUREMENTS AND FINDINGS: a postal questionnaire was sent to women 3-4 years
      after birth. The number of women who remained in the supine position throughout
      the second stage varied between midwifery practices, ranging from 31.3% to 95.9%
      (p<0.001). The majority of women pushed and gave birth in the supine position.
      For positions used throughout the second stage of labour, a stepwise forward
      logistic regression analysis was used to examine effects controlled for other
      factors. Women aged 36 years and highly educated women were less likely to use
      the supine pushing position alone [odds ratio (OR) 0.54, 95% confidence intervals
      (CI) 0.31-0.94; OR 0.40, 95% CI 0.21-0.73, respectively]. Women who pushed for
      longer than 60 minutes and who were referred during the second stage of labour
      were also less likely to use the supine position alone (OR 0.32, 95% CI 0.16
      0.64; OR 0.44, 95% CI 0.23-0.86, respectively). Bivariate analyses were conducted
      for effects on position at the time of birth. Age 36 years, higher education and
      homebirth were associated with giving birth in a non-supine position. KEY
      CONCLUSIONS: the finding that highly educated and older women were more likely to
      use non-supine birthing positions suggests inequalities in position choice.
      Although the Dutch maternity care system empowers women to choose their own place
      of birth, many may not be encouraged to make choices in birthing positions.
      IMPLICATIONS FOR PRACTICE: education of women, midwives, obstetricians and
      perhaps the public in general is necessary to make alternatives to the supine
      position a logical option for all women. Future studies need to establish
      midwife, clinical and other factors that have an effect on women's choice of
      birthing positions, and identify strategies that empower women to make their own
      choices.

PMID- 18082299
TI  - Safety studies of l-alanyl-l-glutamine (l-AG).
AB  - The safety of l-alanyl-l-glutamine (l-AG) derived by fermentation using a
      recombinant Escherichia coli strain containing the l-amino acid alpha-ligase gene
      from Bacillus subtilis, was assessed in acute and subchronic toxicity studies in
      the rat. l-AG was tested in vitro in a bacterial reverse mutation assay and in a
      chromosome aberration assay. l-AG was not acutely toxic when administered to
      Sprague-Dawley rats by gavage at 2000mg/kg bw. In a 14-day range-finding study, l
      AG at up to 5% in the diet was without effect. In the 13-week dietary study,
      there were no toxicologically significant differences between the treated groups
      (1.0, 3.0 and 5.0% l-AG) and the controls (0% and 5% l-AG produced via a
      different method) with respect to body weight gain, feed consumption, feed
      efficiency, or the results of ophthalmological, haematological, clinical
      chemistry, and urinalysis evaluations. Three of 10 high-dose males had mild
      testicular changes, however, these were of exactly the same nature and severity
      as those that occur spontaneously, and were considered unlikely to be treatment
      related. The NOAEL in both males and females was established as the highest dose
      tested at 3129 and 3601mg/kg bw/day, respectively (5.0% in the diet). There was
      no evidence of genotoxicity of l-AG in the Ames assay or in the in vitro CHL cell
      chromosome aberration study.

PMID- 18082300
TI  - Categorization and sensorimotor interaction with objects.
AB  - Three experiments were aimed at verifying whether the modality of interaction
      with objects and the goals defined by the task influences the weight of the
      properties used for categorization. In Experiment 1 we used everyday objects
      (cups and glasses). In order to exclude that the results depended on pre-stored
      categorical knowledge and to assess the role of a purely perceptual property such
      as colour, novel objects were used respectively in Experiment 2 and Experiment 3.
      Participants experienced objects in different modalities of interaction: Vision,
      Vision+Action, Action, and Mirror (they observed an experimenter touching and
      lifting them), then they were submitted to a similarity evaluation task and to a
      more action-based sorting task. Objects varied in intrinsic properties which had
      a different degree of interactivity: Grip, Shape, Size and Colour. Overall Grip,
      the most interactive property, was relevant for categorization, together with
      Size in Experiment 1 and with Shape in Experiment 2 and Experiment 3. The
      relevance of Grip in the sorting task confirms that goal-relevant properties are
      more weighted. The absence of a modality effect is discussed in the framework of
      the theories arguing that the vision of objects and of conspecifics interacting
      with objects automatically activates motor information.

PMID- 18082301
TI  - Aripiprazole resolves symptomatic hyperprolactinemia in a male schizophrenic
      patient.

PMID- 18082302
TI  - Metformin for metabolic dysregulation in schizophrenic patients treated with
      olanzapine.
AB  - The second generation antipsychotic drugs, such as risperidone, olanzapine, and
      quetiapine, are effective in treating patients with schizophrenia and have been
      considered as the first line therapy. Recently, increasing attention has been
      drawn to the potential diabetogenic effect of these novel antipsychotics. The
      goal of this study was to evaluate the effect of metformin treatment on the
      olanzapine-induced metabolic disturbance in schizophrenic patients. Twenty-four
      schizophrenic subjects who had received olanzapine treatment at least 3 months
      were assigned to the therapy with metformin 1500 mg/day for 8 weeks. The
      metabolic parameters were quantitatively assessed at baseline, weeks 2, 4, and 8
      by using the intravenous glucose tolerance test. After an 8-week treatment with
      metformin, the body weight, fasting levels of glucose, triglyceride, and insulin,
      insulin secretion, and insulin resistance significantly decreased. Half of study
      subjects with metabolic syndrome obtained improvement after the metformin trial.
      Subjects' psychopathological condition remained unchanged during the study
      period. The olanzapine-induced metabolic disturbance could be reversed after 8
      week metformin treatment. Based on the results of this study, we hypothesize that
      metformin could modulate the effect of olanzapine-induced metabolic disturbance.

PMID- 18082303
TI  - Modulation of the expression of the pi class of glutathione S-transferase by
      Andrographis paniculata extracts and andrographolide.
AB  - Andrographis paniculata (Ap) is a commonly used herb for traditional medicine in
      many Southeast Asian countries. In the present study, we investigated the effect
      of Ap on the expression of the pi class of glutathione S-transferase (GSTP) in
      rat primary hepatocytes. Hepatocytes were treated with 25 or 50 microg/mL of
      ethanol or ethyl acetate extracts of Ap (ApEE or ApEAE) or 10 or 20 microM
      andrographolide, which is the major active diterpene lactone of Ap, for 48 h.
      ApEE, ApEAE, and andrographolide dose-dependently induced GSTP protein and mRNA
      expression. In a GST activity assay, GST activity was significantly higher in
      cells treated with the maximum concentrations of ApEE, ApEAE, and andrographolide
      than in control cells (P<0.05). The pTA-2713 luciferase reporter construct
      containing rat GSTP enhancer 1 (GPE1) was transiently transfected into Clone 9
      liver cells. Cells treated with ApEE, ApEAE, and andrographolide showed a dose
      dependent increase in luciferase activity. GPE1 deletion abolished the induction
      efficiency of Ap. Also, the induction of GSTP expression by Ap was inhibited by
      wortmannin, which is an inhibitor of the phosphatidylinositol 3-kinase (PI3K)/Akt
      pathway. These results indicate that ApEE, ApEAE, and andrographolide induce GSTP
      expression. This induction is likely related to the PI3K/Akt pathway, and GPE1,
      an enhancer element in GSTP promoter, is essential for the induction.

PMID- 18082304
TI  - An in vitro approach to assess the toxicity of inhaled tobacco smoke components:
      nicotine, cadmium, formaldehyde and urethane.
AB  - One of the first lines of defence to inhaled toxins is the barrier formed by the
      tracheobronchial epithelium, making this the ideal region for studying the
      toxicity of inhaled substances. This study utilises a highly differentiated,
      three-dimensional, in vitro model of human upper respiratory tract epithelium
      (EpiAirway-100) to measure the acute toxicological responses to well
      characterised tobacco smoke components. To determine the suitability of this
      model for screening inhaled toxicants, the EpiAirway tissue model (ETM) was
      treated apically with tobacco smoke components (nicotine, formaldehyde, cadmium,
      urethane) which are known to induce a variety of toxic effects (e.g. cytotoxic,
      thrombogenic, carcinogenic). A range of concentrations were used to model
      different mechanisms and severity of toxicity which were then compared to known
      in vivo responses. Similar trends in stress response occurred, with distinct
      alterations to the tissue in response to all four toxins. At high concentrations,
      cell viability decreased and tight junctions were degraded, but at sub-toxic
      concentrations epithelial resistance (indicating tissue integrity) increased 20
      60% from control. This peak in resistance coincided with an increase in secreted
      protein levels, elevated cytokine release and goblet cell hyperplasia and
      hypertrophy. In conclusion, acute exposure to tobacco smoke components induces
      measurable toxic responses within human respiratory epithelium. Sub-toxic
      concentrations appear to illicit a protective response by increasing mucus
      secretion and mediating immune responses via cytokine release. These responses
      are comparable to human in vivo responses, indicating potential for the ETM as a
      tool for screening the toxicity of inhaled compounds.

PMID- 18082305
TI  - Bonding durability of HEMA-free and HEMA-containing one-step adhesives to dentine
      surrounded by bonded enamel.
AB  - OBJECTIVE: To evaluate the bonding durability of HEMA-free and HEMA-containing
      one-step adhesives to dentine surrounded by bonded enamel after 1-year storage in
      water. MATERIAL AND METHOD: Flat coronal dentine surfaces of extracted human
      molars were prepared, leaving the surrounding enamel. Two one-step self-etch
      adhesive systems: HEMA-containing Tri-S Bond (TSB; Kuraray Medical Inc., Tokyo,
      Japan) and HEMA-free G Bond (GB; GC Co., Tokyo, Japan), were applied to both
      dentine and the surrounding enamel surfaces according to manufacturers'
      instructions. Following resin composite crown (Clearfil AP-X, Kuraray Medical
      Inc., Tokyo, Japan) build-ups, the bonded specimens were stored in 37 degrees C
      water for 24h (control group), 3 months, 6 months and 1 year. After the
      designated periods of water storage, the specimens were serially sectioned
      perpendicular to the adhesive interface into 0.7 mm thick slabs, and then trimmed
      to form hour-glass configurations with a 1mm2 cross-sectional area. The micro
      tensile bond strength (muTBS) test was carried out at a crosshead speed of
      1.0mm/min. The muTBS data were statistically analyzed using two-way ANOVA, t
      test, and Tukey's HSD post hoc multiple comparison tests (alpha=0.05). RESULTS:
      After 1 year water of storage, the bond strength of TSB to dentine was
      significantly lower compared with the 1-day, 3-month and 6-month groups (p<0.05).
      On the other hand, the muTBS of GB decreased over time, but there was no
      significant difference between the experimental periods (p>0.05). CLINICAL
      SIGNIFICANCE: Bonded enamel margins may not maintain the integrity of the resin
      dentine interface created by HEMA-free and HEMA-containing one-step adhesives.

PMID- 18082306
TI  - Use of temporary inferior vena cava filter placement in pregnant women near term.

PMID- 18082307
TI  - Recurrent Kikuchi-Fujimoto necrotizing lymphadenitis during pregnancy.

PMID- 18082308
TI  - Clinical scale ex vivo expansion of cord blood-derived outgrowth endothelial
      progenitor cells is associated with high incidence of karyotype aberrations.
AB  - OBJECTIVE: Endothelial progenitor cells (EPCs) are involved in neovessel
      formation. So far, therapeutic angiogenesis is hampered by the low frequency and
      limited proliferative potential of these cells isolated from peripheral blood.
      Recently, it has been shown that cord blood-derived EPCs (CB EPCs) can be ex vivo
      expanded on a clinical scale. In this study, we evaluated the expansion potential
      of CB EPCs together with their phenotypic, functional, and chromosomal stability
      over time. MATERIALS AND METHODS: Flow cytometry, in vitro tube formation, and
      proliferation assays were performed to characterize CB EPC-derived cells.
      Chromosomal stability was evaluated by karyotype analysis. In vitro and in vivo
      tumorigenicity was evaluated by soft agar assay and injection into nonobese
      diabetic/severe combined immunodeficient mice, respectively. RESULTS: We showed
      that CB EPC-derived cells displayed phenotypic and functional features of EPCs,
      although a process of maturation was observed over time. Although we confirmed
      that CB EPCs have a greater expansion potential compared to peripheral blood
      EPCS, we observed a high incidence of cytogenetic alterations (71%) in the
      expanded endothelial cell population, even at early times of culture. In two
      cases, spontaneous transformation in vitro was documented, but none of the
      samples tested showed tumorigenic potential in vivo. Conversely, no karyotype
      alterations have been observed on peripheral blood EPCs-derived cells.
      CONCLUSIONS: We confirm that CB represents a good source for clinical ex vivo
      expansion of EPCs. However, because of high frequency of karyotype alterations,
      these cells cannot be considered free of risk in clinical application.

PMID- 18082309
TI  - Cadmium adsorption on vermiculite, zeolite and pumice: batch experimental
      studies.
AB  - Batch experiments were performed to evaluate the combined effects of ionic
      activity, pH, and contact time on the cadmium sorption in three different
      minerals, vermiculite, zeolite, and pumice, commonly employed as substrata in
      nurseries and recently considered for their potential use in remediation methods.
      The extent of cadmium sorption was vermiculite>zeolite>pumice, as shown by the
      Langmuir and Freundlich parameters, and it was highly dependent on mineral
      characteristics. The percentage of cadmium sorption in zeolite and vermiculite
      did not depend on cadmium concentration, while in pumice this percentage was
      positively correlated to the initial cadmium concentration. At low cadmium
      concentrations (30-120 microM), the metal sorbed on zeolite was mainly present in
      the nonexchangeable form (70%) at levels much higher than those found for
      vermiculite and pumice. The primary variable responsible for determination of
      cadmium mobility in these minerals was confirmed to be pH. The ionic
      concentrations of Hoagland nutrient solution were significantly modified by both
      pH and mineral composition, while the presence of cadmium caused no changes. With
      vermiculite and zeolite, the time-course of cadmium sorption was related to
      mineral composition to a greater extent than to cadmium concentration. While with
      pumice, the percentage of cadmium sorbed after 6 weeks was lower than with the
      other two minerals, and it was inversely correlated to the initial cadmium
      concentration.

PMID- 18082310
TI  - Successful de-fragmentation of woodland by planting in an agricultural landscape?
      An assessment based on landscape indicators.
AB  - Habitat fragmentation is the focus of much conservation concern and associated
      research. In some countries, such as Britain, the main phase of fragmentation
      occurred centuries ago and the focus of conservation management is now on
      restoration and recovery. Scenario studies have suggested that spatial targeting
      is preferable if landscape scale restoration is to be achieved, and that this
      should bring greater benefits than site-focussed activities but this has rarely
      been tested in practice. In Britain, woodland expansion has been encouraged
      through a number of financial incentives, which have evolved from instruments
      that encouraged almost any addition to the potential woodland resource, to grant
      schemes that have set out to restore connectivity to remnant ancient woodland.
      This study assessed the degree of de-fragmentation achieved by woodland expansion
      on the Isle of Wight and in particular the success of spatial targeting of new
      woodland planting implemented through grant aid in the JIGSAW (Joining and
      Increasing Grant Scheme for Ancient Woodland) scheme. Five steps in the re
      development of broad-leaved woodland were tested using eight indicators - six
      commonly used landscape metrics, and two ecologically scaled indicators derived
      from application of least-cost network evaluation. Only half of the measures
      indicated de-fragmentation over the whole sequence of five steps. However, the
      spatial targeting did appear successful, when compared to equivalent untargeted
      grant-aided woodland expansion, and resulted in positive change to six of the
      eight indicators. We discuss the utility of the indicators and ways in which
      future targeting could be supported by their application.

PMID- 18082311
TI  - The geography of conflict between elk and agricultural values in the Cypress
      Hills, Canada.
AB  - Complex ecological issues like depredation and its management are determined by
      multiple factors acting at more than one scale and are interlinked with complex
      human social and economic behaviour. Depredation by wild herbivores can be a
      major obstacle to agricultural community support for wildlife conservation. For
      three decades, crop and fence damage, competition with livestock for native
      rangeland and tame pasture, and depredation of stored feed by elk (Cervus elaphus
      canadensis) have been the cause of conflict with agricultural producers in the
      Cypress Hills, Alberta and Saskatchewan. Tolerance of elk presence on private
      lands is low because few benefits accrue to private landowners; rather they
      largely perceive elk as a public resource produced at their expense. Government
      management actions have focused on abatement inputs (e.g., population reduction;
      fencing) and compensation, but incentives to alter land use patterns (crop choice
      and location) in response to damages have not been considered. Nor has there been
      information on spatial structure of the elk population that would allow targeted
      management actions instead of attempting to manage the entire population. In this
      study we analysed the spatial structure of the Cypress Hills elk population, the
      distribution of the elk harvest in relation to agricultural conflicts, developed
      models of the spatial patterns of conflict fields, and evaluated compensation
      patterns for damage by wild herbivores. We propose modifications to current
      abatement and compensation programs and discuss alternative approaches involving
      changes to agricultural land use patterns that may reduce the intensity of
      conflicts with elk, and increase the acceptance capacity of landowners.

PMID- 18082312
TI  - Microbial and nutrient contaminants of fresh and coastal waters.

PMID- 18082313
TI  - Improvement of the activity of anaerobic sludge by low-intensity ultrasound.
AB  - This paper aims to study the enhancement effect of low-intensity ultrasound on
      anaerobic sludge activity and the efficiency of anaerobic wastewater treatment.
      Dehydrogenate activity (DHA) and the content of coenzyme F(420) were detected to
      indicate the change of activity of anaerobic sludge induced by ultrasound at 35
      kHz. Single-factor and multiple-factor optimization experiments showed that the
      optimal ultrasonic intensity and irradiation period were 0.2 W/cm(2) and 10 min,
      respectively, and the biological activity was enhanced dramatically under the
      optimal condition. The chemical oxygen demand (COD) removal efficiency was
      increased by ultrasonic treatment and the COD in the effluent was 30% lower than
      that of the control (without exposure). The hypothetical mechanism of biological
      activity enhancement by ultrasound was also discussed according to the results.

PMID- 18082314
TI  - Impact of land use on the biodiversity integrity of the moist sub-biome of the
      grassland biome, South Africa.
AB  - South Africa's moist grassland harbours globally significant biodiversity,
      supplies essential ecosystem services, supports crop and livestock agriculture,
      forestry and settlement, yet is poorly conserved. Ongoing transformation and
      limited opportunity for expanding the protected area network require instead that
      biodiversity conservation is 'mainstreamed' within other land uses. This exercise
      sought to identify the relative compatibility of 10 land uses (conservation,
      livestock or game ranching, tourism/recreation, rural settlement, dryland
      cropping, irrigated cropping, dairy farming, plantation forestry, and urban
      settlement) with maintaining biodiversity integrity. This was assessed using 46
      indicators for biodiversity integrity that covered landscape composition,
      structure, and functioning. Data was integrated into a single measure per land
      use through application of the analytic hierarchy process, with supporting
      information gained from interviews with experts. The rank order of importance
      amongst indicators was landscape structure, functioning and composition.
      Consistent differences among land uses for all three categories revealed two
      clear groupings. Conservation, livestock or game ranching had the lowest impact
      and retained substantial natural asset, while that for tourism/recreation was
      intermediate. All other land uses had a severe impact. Impact on biodiversity
      integrity depended mainly on the extent of transformation and fragmentation,
      which accounted for the greatest impact on habitats and species, and impairment
      of landscape functioning. It is suggested that a strategic intervention for
      maintaining biodiversity integrity of moist grassland is to support livestock or
      game ranching and limit ongoing urban sprawl.

PMID- 18082315
TI  - Sorption of styrene from aqueous solutions with oil absorptive resin.
AB  - We demonstrated the utility of oil-absorbing 4-tert-butylstyrene-divinylbenzene
      ethylene/propylene/diene resins in the removal of environmental hormones such as
      styrene from water. A maximum treatment efficiency of 99.47% was observed when
      using a static process, while the dynamic process yielded a maximum efficiency of
      96.25%. The sorption efficiency was greater for solutions containing higher
      initial concentrations of styrene and for extended static contact times, but
      decreased with increasing hydraulic retention time. The influences of styrene
      concentration, sorption time, and hydraulic retention time on sorption efficiency
      were successfully predicted using a polynomial equation, sigmoidal function and
      exponential decay equation, respectively. It was found that the sorption process
      was well described by a first-order kinetic model.

PMID- 18082316
TI  - Web-based surveys as an alternative to traditional mail methods.
AB  - Environmental economists have long used surveys to gather information about
      people's preferences. A recent innovation in survey methodology has been the
      advent of web-based surveys. While the Internet appears to offer a promising
      alternative to conventional survey administration modes, concerns exist over
      potential sampling biases associated with web-based surveys and the effect these
      may have on valuation estimates. This paper compares results obtained from a
      travel cost questionnaire of visitors to Fraser Island, Australia, that was
      conducted using two alternate survey administration modes; conventional mail and
      web-based. It is found that response rates and the socio-demographic make-up of
      respondents to the two survey modes are not statistically different. Moreover,
      both modes yield similar consumer surplus estimates.

PMID- 18082317
TI  - Core biopsies of renal tumors: a study on diagnostic accuracy, interobserver, and
      intraobserver variability.
AB  - OBJECTIVE: The diagnostic accuracy of in-bench core biopsies (CBs) from renal
      masses, and the interobserver and intraobserver variability in pathological
      subtyping of renal tumors were assessed. METHODS: We performed two CBs in 62
      consecutive renal masses suspected for renal cell carcinoma (RCC), obtained after
      radical or partial nephrectomy and, in one case, after autopsy. Routine
      hematoxylin-eosin (HE)-stained sections from each CB were evaluated by five
      pathologists on two occasions. The surgical specimen was the reference standard.
      Diagnostic accuracy and the generalized kappa for intraobserver and interobserver
      agreement were calculated. RESULTS: Five tumors were benign and 57 malignant.
      Eight percent to 16% of the CBs were considered inadequate for diagnosis. In 0-8%
      of the cases, the pathologist could not discriminate between a benign or
      malignant tumor. Overall accuracy ranged from 77% to 90%. Sensitivity (79-100%)
      and positive predictive value (100%) were high with narrow 95% confidence
      interval (95%CI). Specificity (100%) was high but negative predictive value (29%
      100%) varied, with wide 95% CI. Interobserver agreement was fair to almost
      perfect (kappa=-0.010 to 0.830) for the different subtypes. In 64-81% of the CBs,
      the subtype was correctly classified. Intraobserver agreement was substantial
      (mean kappa=0.628) for all pathologists. CONCLUSION: Diagnostic accuracy of CBs
      was high, with a diagnostic yield varying between 84% and 92%. Pathological
      subtyping of CBs was highly reproducible with the exception of the chromophobe
      renal cell carcinoma, which was problematic on HE-stained sections only.

PMID- 18082318
TI  - Editorial comment on: core biopsies of renal tumors: a study on diagnostic
      accuracy, interobserver, and intraobserver variability.

PMID- 18082319
TI  - Editorial comment on: core biopsies of renal tumors: a study on diagnostic
      accuracy, interobserver, and intraobserver variability.

PMID- 18082320
TI  - Intrafascial nerve-sparing endoscopic extraperitoneal radical prostatectomy.
AB  - OBJECTIVES: Based on our recently published anatomic studies, we present the most
      recent refinement of the endoscopic extraperitoneal radical prostatectomy
      (EERPE), the intrafascial nerve-sparing EERPE (nsEERPE). METHODS: As part of the
      intrafascial technique, the dissection plane is directly on the prostatic
      capsule, freeing the prostate laterally from its thin surrounding fascia that
      contains small vessels and nerves. The technique enables puboprostatic ligament
      preservation, leaving intact endopelvic fascia, periprostatic fascia, and
      neurovascular bundles. The operation was performed in 150 patients with
      indications for nerve-sparing procedure. RESULTS: The mean operative time was 131
      min (range: 50-210 min) and the mean catheterization time was 5.9 d (range: 4-20
      d). Twelve months postoperatively, 94.3% of the patients were continent (no need
      for pads), 4.6% had minimal stress incontinence, and one patient required >2
      pads/d. At the 12-mo follow-up, the potency rates (erections sufficient for
      intercourse with or without the use of phosphodiesterase 5 [PDE5] inhibitors) of
      the patients who underwent bilateral intrafascial nsEERPE were 89.7% (age: 44-55
      yr), 81.1% (age: 56-65 yr), and 61.9% (age: >65 yr). Positive surgical margins in
      pT2 and pT3 tumors were 4.5% and 29.4%, respectively. CONCLUSIONS: The
      intrafascial nsEERPE enables the dissection of the prostate with limited trauma
      to the surrounding fascias and the enclosed neurovascular bundles. We propose
      that the preserved neurovascular bundles with intrafascial nsEERPE are more
      viable. The results advocate this proposition.

PMID- 18082322
TI  - Bypassing cancer drug resistance by activating multiple death pathways--a
      proposal from the study of circumventing cancer drug resistance by induction of
      necroptosis.
AB  - Cancer drug resistance is a complex, dynamic, and "elusive" system rather than
      merely a matter of some drug-resistant factors. Current pharmacological
      approaches aim to restore the efficacy of the standard chemotherapy against drug
      resistant cancers via reactivating apoptosis and inhibiting drug transporters,
      simply because the current available anticancer drugs mostly induce apoptosis and
      many of them are the substrates/inducers of the drug transporters. However, since
      there are so many different types of defects in apoptotic pathways as well as
      numerous drug transporters, which could simultaneously contribute to cancer drug
      resistance, to succeed in the approach is theoretically possible but practically
      extremely difficult. To circumvent cancer drug resistance is an alternative
      choice. Since there are multiple death pathways with molecular mechanisms
      distinct from each other, we previously proposed that the barriers set up in
      cancer cells to avoid one pathway were not problems for another. Thus, no matter
      how dynamic, complex, and "elusive" the resistance occurs along one death pathway
      (e.g., apoptosis), the resistance would be sequestered within this pathway, and
      would not affect another death pathway with mechanisms distinct from the former,
      and vice versa, e.g., apoptotic resistant cancers can be sensitive to an
      induction of a nonapoptotic death. Indeed, we recently demonstrated that the
      cancer cells resistant to apoptotic inducers such as anthracycline antibiotics,
      vinca alkaloids, epipodophylotoxins, were sensitive to necroptotic inducers such
      as shikonin. Therefore, to bypass cancer drug resistance is principally
      achievable by simultaneously activating multiple death pathways using combined
      classes of death inducers (apoptosis, autophagy, necroptosis, etc.). Although
      each class of death inducers has its own action window and limit in killing
      cancer cells, a rationalized combination of several classes of death inducers
      that compliment each other would maximize their efficacy while simultaneously
      minimizing their weakness. Such "mixed bullets" would probably achieve a good
      therapeutic efficacy by bypassing cancer drug resistance.

PMID- 18082323
TI  - Speciation of chromium in water samples with cloud point extraction separation
      and preconcentration and determination by graphite furnace atomic absorption
      spectrometry.
AB  - A novel method has been developed for the speciation of chromium in natural water
      samples based on cloud point extraction (CPE) separation and preconcentration,
      and determination by graphite furnace atomic absorption spectrometry (GFAAS). In
      this method, Cr(III) reacts with 1-phenyl-3-methyl-4-benzoylpyrazol-5-one (PMBP)
      yielding a hydrophobic complex, which then is entrapped in the surfactant-rich
      phase, whereas Cr(VI) remained in aqueous phase. Thus, separation of Cr(III) and
      Cr(VI) could be realized. Total chromium was determined after the reduction of
      Cr(VI) to Cr(III) by using ascorbic acid as reducing reagent. PMBP was used not
      only as chelating reagent in CPE procedure, but also as chemical modifier in
      GFAAS determination of chromium. The detection limit for Cr(III) was 21 ng L(-1)
      with an enrichment factor of 42, and the relative standard deviation was 3.5%
      (n=7, c=10 ng mL(-1)). The proposed method has been applied to the speciation of
      chromium in natural water samples with satisfactory results.

PMID- 18082324
TI  - Photocatalytic treatment of black table olive processing wastewater.
AB  - The photocatalytic treatment of an effluent from black table olive processing
      over TiO2 suspensions was investigated. The study focused on the effect of
      various operating parameters on the treatment efficiency including initial
      organic load, catalyst type, concentration and reuse, and addition of hydrogen
      peroxide. Initial organic load, expressed in terms of chemical oxygen demand
      (COD), was studied in the range 1-8 g/L, anatase TiO2 concentrations in the range
      0.25-2 g/L and H2O2 concentrations in the range 0.025-0.15 g/L. Treatment
      efficiency, which was assessed in terms of COD, total phenols, aromatics and
      color reduction, generally increased with decreasing initial COD and increasing
      contact time, catalyst and H2O2 concentrations; however, for H2O2 there was a
      maximum dosage above which performance deteriorated. Depending on the conditions
      employed, nearly complete decoloration (>90%) could be achieved, while
      mineralization never exceeded 50%. Shake-flask tests with non-acclimated
      activated sludge showed that both the original and photocatalyzed effluents were
      degradable aerobically with the biodegradation rate of the original effluent
      being three times greater than the oxidized one. On the other hand,
      photocatalytic oxidation of the original effluent was at least two orders of
      magnitude faster than its biological oxidation to achieve comparable levels of
      degradation.

PMID- 18082325
TI  - Environmental feasibility of using coal ash as a fill material to raise the
      ground level.
AB  - Batch leach tests (BLTs) and column leach tests (CLTs) were conducted on bottom
      ash (BA), lagoon ash (LA), soil (S), and bottom ash-soil (BA-S) and lagoon ash
      soil (LA-S) mixtures to evaluate the environmental feasibility of using these as
      fill materials to raise the ground level at construction sites. For the BLTs, the
      leachability of the elements (i.e., Cr, Mn, Ni, and Zn) generally increased with
      decreasing pH from 6.3 to 3.0. In addition, the concentration of all the elements
      analyzed in the leachates increased with decreasing the liquid-to-solid (L/S)
      ratio. Freezing-thawing cycles had no significant effect on the leachability of
      the elements found in the BLTs. The initial concentrations of the leachates from
      the CLTs were higher than those of the leachates from the BLTs regardless of the
      materials tested due to the lower L/S ratio. The initial concentrations of As,
      Ni, Mn, Se, Cl-, and SO4(2-) in the leachates from the CLTs for the LA, BA, and
      LA-S and BA-S mixtures exceeded the drinking water standards (DWSs), which
      suggests that these materials may pose a risk to groundwater when these materials
      are used in areas where there is little dilution.

PMID- 18082326
TI  - Determination of trace aluminum in biological and water samples by cloud point
      extraction preconcentration and graphite furnace atomic absorption spectrometry
      detection.
AB  - A cloud point extraction (CPE) method for the preconcentration of trace aluminum
      prior to its determination by graphite furnace atomic absorption spectrometry
      (GFAAS) has been developed. The CPE method is based on the complex of Al(III)
      with 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (PMBP), and then entrapped in non
      ionic surfactant Triton X-114. PMBP was used not only as chelating reagent in CPE
      preconcentration, but also as chemical modifier in GFAAS determination. The main
      factors affecting CPE efficiency, such as pH of sample solution, concentration of
      PMBP and Triton X-114, equilibration temperature and time, were investigated in
      detail. An enrichment factor of 37 was obtained for the preconcentration of
      Al(III) with 10 mL solution. Under the optimal conditions, the detection limit of
      this method for Al(III) is 0.09 ng mL(-1), and the relative standard deviation is
      4.7% at 10 ng mL(-1) Al(III) level (n=7). The proposed method has been applied
      for determination of trace amount of aluminum in biological and water samples
      with satisfactory results.

PMID- 18082327
TI  - 3-D reconstruction of the atomic positions in a simulated gold nanocrystal based
      on discrete tomography: prospects of atomic resolution electron tomography.
AB  - A novel reconstruction procedure is proposed to achieve atomic resolution in
      electron tomography. The method exploits the fact that crystals are discrete
      assemblies of atoms (atomicity). This constraint enables us to obtain a three
      dimensional (3-D) reconstruction of test structures from less than 10 projections
      even in the presence of noise and defects. Phase contrast transmission electron
      microscopy (TEM) images of a gold nanocrystal were simulated in six different
      zone axes. The discrete number of atoms in every column is determined by
      application of the channelling theory to reconstructed electron exit waves. The
      procedure is experimentally validated by experiments with gold samples. Our
      results show that discrete tomography recovers the shape of the particle as well
      as the position of its 309 atoms from only three projections. Experiments on a
      nanocrystal that contains several missing atoms, both on the surface and in the
      core of the nanocrystal, while considering a high noise level in each simulated
      image were performed to prove the stability of the approach to reconstruct
      defects. The algorithm is well capable of handling structural defects in a highly
      noisy environment, even if this causes atom count "errors" in the projection
      data.

PMID- 18082328
TI  - Aromatase inhibitor-induced arthralgia: clinical experience and treatment
      recommendations.
AB  - It is well documented that the aromatase inhibitors (AIs) are superior to
      tamoxifen as adjuvant endocrine therapy in postmenopausal women with hormone
      receptor-positive breast cancer. However, compared with tamoxifen, an elevated
      incidence of arthralgia has been observed during AI treatment. Concerns have been
      raised that AI-induced arthralgia may dissuade patients from completing their
      full AI treatment course, and may also deter physicians from prescribing an AI if
      they feel that patients may be at risk of permanent joint damage. Patient
      education about the possibility of experiencing arthralgia, and effective
      management of symptoms if they appear, are important in helping patients adhere
      to AI treatment, and consequently improving breast cancer outcomes. In this
      paper, we discuss the potential mechanisms behind AI-induced arthralgia, review
      the frequency with which arthralgia occurs, and propose for the first time an
      algorithm specifically for the treatment of AI-induced arthralgia. As with joint
      pain in non-breast cancer patients, a sequential approach to disease management
      is recommended, involving modifying the patient's lifestyle in addition to taking
      a stratified approach to pharmacological intervention with analgesia and anti
      inflammatory medication. Knowing that joint symptoms can be managed in most
      patients may encourage patient-physician communication and treatment compliance.

PMID- 18082329
TI  - 5-HT excites globus pallidus neurons by multiple receptor mechanisms.
AB  - Anatomical and neurochemical studies indicated that the globus pallidus receives
      serotonergic innervation from raphe nuclei but the membrane effects of 5-HT on
      globus pallidus neurons are not entirely clear. We address this question by
      applying whole-cell patch-clamp recordings on globus pallidus neurons in immature
      rat brain slices. Under current-clamp recording, 5-HT depolarized globus pallidus
      neurons and increased their firing rate, an action blocked by both 5-HT(4) and 5
      HT(7) receptor antagonists and attributable to an increase in cation
      conductance(s). Further experiments indicated that 5-HT enhanced the
      hyperpolarization-activated inward conductance which is blocked by 5-HT(7)
      receptor antagonist. To determine if 5-HT exerts any presynaptic effects on
      GABAergic and glutamatergic inputs, the actions of 5-HT on synaptic currents were
      studied. At 10 microM, 5-HT increased the frequency of spontaneous inhibitory
      postsynaptic currents (sIPSCs) but had no effect on both the frequency and
      amplitude of miniature inhibitory postsynaptic currents (mIPSCs). However, 5-HT
      at a higher concentration (50 microM) decreased the frequency but not the
      amplitude of the mIPSCs, indicating an inhibition of GABA release from the
      presynaptic terminals. This effect was sensitive to 5-HT(1B) receptor antagonist.
      In addition to the presynaptic effects on GABAergic neurotransmission, 5-HT at 50
      microM had no consistent effects on glutamatergic neurotransmission,
      significantly increased the frequency of miniature excitatory postsynaptic
      currents (mEPSCs) in 4 of 11 neurons and decreased the frequency of mEPSCs in 3
      of 11 neurons. In conclusion, we found that 5-HT could modulate the excitability
      of globus pallidus neurons by both pre- and post-synaptic mechanisms. In view of
      the extensive innervation by globus pallidus neurons on other basal ganglia
      nuclei, this action of 5-HT originated from the raphe may have a profound effect
      on the operation of the entire basal ganglia network.

PMID- 18082330
TI  - Effect of social isolation on CB1 and D2 receptor and fatty acid amide hydrolase
      expression in rats.
AB  - Rearing rats in isolation has been shown to produce behavioral and neurochemical
      alterations similar to those observed in psychoses such as schizophrenia. Also, a
      dysregulation in both the endocannabinoid and dopaminergic systems has been
      implicated in schizophrenia. The aim of this study was to determine if there are
      differences in CB1 receptor and fatty acid amide hydrolase (FAAH) protein
      expression, as well as D2 dopamine receptor expression in different brain regions
      in rats reared in different environmental conditions. Twenty-one-day-old male
      Sprague-Dawley rats were either reared in individual cages (isolated rats) or in
      group cages of six per cage (group-housed rats) for 8 weeks. Quantitative
      fluorescence immunohistochemistry was performed on brain slices using antibodies
      specific to the CB1 or D2 receptor, or the enzyme FAAH. Raising rats in isolation
      led to a significant decrease in CB1 receptor expression in the caudate putamen
      and the amygdala, a significant increase in FAAH expression in the caudate
      putamen and the nucleus accumbens core and shell, and no significant change in D2
      receptor expression in any region studied. These results indicate that the
      endocannabinoid system is altered in an animal model of aspects of psychosis.
      This implies that rearing rats under different housing conditions may provide new
      insight into the role of the endocannabinoid system in the development of
      psychoses.

PMID- 18082331
TI  - The sodium-activated potassium channel Slack is modulated by hypercapnia and
      acidosis.
AB  - Slack (Slo 2.2), a member of the Slo potassium channel family, is activated by
      both voltage and cytosolic factors, such as Na(+) ([Na(+)](i)) and Cl(-) ([Cl(
      )](i)). Since the Slo family is known to play a role in hypoxia, and since
      hypoxia/ischemia is associated with an increase in H(+) and CO(2)
      intracellularly, we hypothesized that the Slack channel may be affected by
      changes in intracellular concentrations of CO(2) and H(+). To examine this, we
      expressed the Slack channel in Xenopus oocytes and the Slo 2.2 protein was
      allowed to be inserted into the plasma membrane. Inside-out patch recordings were
      performed to examine the response of Slack to different CO(2) concentrations
      (0.038%, 5%, 12%) and to different pH levels (6.3, 6.8, 7.3, 7.8, 8.3). In the
      presence of low [Na(+)](i) (5 mM), the Slack channel open probability decreased
      when exposed to decreased pH or increased CO(2) in a dose-dependent fashion (from
      0.28+/-0.03, n=3, at pH 7.3 to 0.006+/-0.005, n=3, P=0.0004, at pH 6.8; and from
      0.65+/-0.17, n=3, at 0.038% CO(2) to 0.22+/-0.07, n=3, P=0.04 at 12% CO(2)). In
      the presence of high [Na(+)](i) (45 mM), Slack open probability increased (from
      0.03+/-0.01 at 5 mM [Na(+)](i), n=3, to 0.11+/-0.01, n=3, P=0.01) even in the
      presence of decreased pH (6.3). Since Slack activity increases significantly when
      exposed to increased [Na(+)](i), even in presence of increased H(+), we propose
      that Slack may play an important role in pathological conditions during which
      there is an increase in the intracellular concentrations of both acid and Na(+),
      such as in ischemia/hypoxia.

PMID- 18082332
TI  - The interaction of Nogo-66 receptor with Nogo-p4 inhibits the neuronal
      differentiation of neural stem cells.
AB  - The Nogo-66 receptor (NgR) has been found throughout axons in the adult and
      maturing CNS. An interaction of Nogo on the oligodendrocyte surface with NgR on
      axons has been suggested to play an important role in limiting axonal growth. In
      our study, we found that neural stem cells (NSCs) derived from the spinal cords
      of rats expressed NgR significantly. After normal NSCs differentiation, the
      average neuronal neurite length was 97.80+/-6.97 microm and the percentage of
      differentiated neurons was 34.73+/-5.21% 3 days after the differentiation was
      initiated in vitro. If NSCs were allowed to differentiate in the presence of Nogo
      p4 (the active segment of Nogo-66), the average neurite length and the percentage
      of differentiated neurons were decreased, respectively, to 60.31+/-6.58 microm
      and 10.26+/-1.22%. An siRNA-mediated knockdown of NgR on NSCs could reverse the
      inhibitory effect of Nogo-p4 and restore the average neuronal neurite length as
      well as the percentage of differentiated neurons to 94.01+/-8.37 microm and
      31.84+/-4.03%. These results deepen our knowledge about the distribution of NgR
      and provide a possible strategy of treating NSCs to ameliorate neuronal
      differentiation after transplantation.

PMID- 18082333
TI  - The effect of mood stabilizer lithium on expression and activity of glutathione s
      transferase isoenzymes.
AB  - Chronic treatment with the mood stabilizer lithium is required to generate its
      mood stabilizing effect in the treatment of bipolar disorder. Our recent studies
      have shown that chronic lithium treatment increases mRNA and protein levels of
      the cytosolic glutathione s-transferase (GST) M1 isoenzyme. Cytosolic GST
      encompasses a family of detoxification enzymes that include four main classes:
      alpha (A), mu (M), pi (P) and theta (T). The purpose of this study is to examine
      the effect of lithium on GST isoenzymes that are expressed in brain, and
      determine the role of GST in the neuroprotective effects of lithium against
      oxidative stress. We found in primary cultured rat cerebral cortical cells that
      chronic lithium treatment not only increased GST M1 mRNA levels, but also
      increased GST M3, M5 and A4 mRNA levels. Chronic lithium treatment increased GST
      enzyme activity when 1-chloro-2, 4-dinitrobenzene and 4-hydroxynonenal were used
      as substrates. In addition, we found that chronic lithium treatment inhibited
      reactive oxygen metabolite H(2)O(2)-induced cell death and DNA fragmentation in
      primary cultured rat cerebral cortical cells, while GST inhibitor ethacrynic acid
      reduced the neuroprotective effect of lithium against H(2)O(2)-induced cell death
      and DNA fragmentation. Since GST conjugates glutathione, the major antioxidant in
      brain, with a variety of oxidized products to form nontoxic products, and plays
      an important role in cellular protection against oxidative stress, our findings
      suggest that lithium selectively targets GST isoenzymes in order to produce
      neuroprotective effects against oxidative stress.

PMID- 18082334
TI  - Characterization of heterogeneous glial cell populations involved in dehydration
      induced proliferation in the adult rat neurohypophysis.
AB  - The adult neurohypophysis (NH) is a well-established site of CNS plasticity: its
      glial cells, the pituicytes, reorganize their structure and undergo increased
      proliferation in response to stimulations such as dehydration. However, it
      remains to be clarified whether the newly-formed cells derive from pituicytes re
      entering the cell cycle or from glial precursors or stem cells. Here, we first
      analyze the expression of several glial markers in the adult rat NH and
      demonstrate that the pituicytes constitute a heterogeneous population. In
      particular, we identify a distinct subtype of glial cells expressing the
      oligodendrocyte precursor marker platelet-derived growth factor receptor alpha
      (pdgfralpha). In addition, adult NH explants can give rise to migratory
      precursors able to differentiate into mature oligodendrocytes, unlike NH cells in
      vivo. This led us to hypothesize that the adult NH could contain immature cells,
      therefore we used a neurosphere-forming assay to test for the presence of stem or
      progenitor cells. Adult NH cells can generate bipotent primary neurospheres but
      not secondary ones, suggesting that the structure contains glial progenitors but
      probably not stem cells. Finally, when the NH is stimulated by dehydration, we
      observe an increase in cell proliferation associated with an increase in cell
      death. By identifying the cells incorporating bromodeoxyuridine (BrdU) or
      positive for Ki67, we demonstrate that this increased proliferation concerns all
      glial cell types in the adult NH, including the pdgfralpha+ cells. Our study
      shows that the NH is a complex structure composed of multiple glial subtypes,
      which all participate in the physiological response to dehydration.

PMID- 18082336
TI  - Developmental expression and distribution of opioid receptors in zebrafish.
AB  - Zebrafish is a novel experimental model that has been used in developmental
      studies as well as in the study of pathological processes involved in human
      diseases. It has been demonstrated that the endogenous opioid system is involved
      in developmental mechanisms. We have studied the relationship between the
      different embryonic stages and opioid receptor expression for the four known
      opioid receptors in zebrafish (mu, delta 1, delta 2 and kappa). The mu opioid
      receptor is detected at higher levels than the other opioid receptors before the
      midblastula transition and during the segmentation period. The delta duplicate 2
      exhibits only one peak of expression at 21 h postfertilization (hpf), when the
      motor nervous system is forming. The kappa receptor is expressed at very low
      levels. In situ hybridization studies at 24 hpf show that the opioid receptors
      are widely distributed in zebrafish CNS and at 48 hpf their localization is
      detected in more defined structures. Our results support specific implications of
      the opioid receptors in developmental processes such as morphogenesis of the CNS,
      neurogenesis, neuroprotection and development of neuromuscular and digestive
      system. Pain-related alterations can be a consequence of changes in the
      endogenous opioid system during development, hence we provide important
      information that might help to solve pain-related pathological situations.

PMID- 18082335
TI  - alpha-Isoform of calcium-calmodulin-dependent protein kinase II and postsynaptic
      density protein 95 differentially regulate synaptic expression of NR2A- and NR2B
      containing N-methyl-d-aspartate receptors in hippocampus.
AB  - N-methyl-d-aspartate receptors (NMDARs) are critical determinants of
      bidirectional synaptic plasticity, however, studies of NMDAR function have been
      based primarily on pharmacological and electrophysiological manipulations, and it
      is still debated whether there are subunit-selective forms of long-term
      potentiation (LTP) and long-term depression (LTD). Here we provide
      ultrastructural analyses of axospinous synapses in cornu ammonis field 1 of
      hippocampus (CA1) stratum radiatum of transgenic mice with mutations to two key
      underlying postsynaptic density (PSD) proteins, postsynaptic density protein 95
      (PSD-95) and the alpha-isoform of calcium-calmodulin-dependent protein kinase II
      (alphaCaMKII). Distribution profiles of synaptic proteins in these mice reveal
      very different patterns of subunit-specific NMDAR localization, which may be
      related to the divergent phenotypes of the two mutants. In PSD-95, Dlg, ZO-1/Dlg
      homologous region (PDZ) 3-truncated mutant mice in which LTD could not be induced
      but LTP was found to be enhanced, we found a subtle, yet preferential
      displacement of synaptic N-methyl-d-aspartate receptor subunit 2B (NR2B) subunits
      in lateral regions of the synapse without affecting changes in the localization
      of N-methyl-d-aspartate receptor subunit 2A (NR2A) subunits. In persistent
      inhibitory alphaCaMKII Thr305 substituted with Asp in alpha-isoform of calcium
      calmodulin kinase II (T305D) mutant mice with severely impaired LTP but stable
      LTD expression, we found a selective reduction of NR2A subunits at both the
      synapse and throughout the cytoplasm of the spine without any effect on the NR2B
      subunit. In an experiment of mutual exclusivity, neither PSD-95 nor alphaCaMKII
      localization was found to be affected by mutations to the corresponding PSD
      protein suggesting that they are functionally independent of the other in the
      regulation of NR2A- and NR2B-containing NMDARs preceding synaptic activity.
      Consequently, there may exist at least two distinct PSD-95 and alphaCaMKII
      specific NMDAR complexes involved in mediating LTP and LTD through opposing
      signal transduction pathways in synapses of the hippocampus. The contrasting
      phenotypes of the PSD-95 and alphaCaMKII mutant mice further establish the
      prospect of an independent and, possibly, competing mechanism for the regulation
      of NMDAR-dependent bidirectional synaptic plasticity.

PMID- 18082338
TI  - Factors associated with history of non-fatal overdose among opioid users in the
      Swedish criminal justice system.
AB  - BACKGROUND: Overdose (OD) is a common cause of death in opioid users. Also, many
      current opioid users report a history of non-fatal OD. The present study aimed to
      identify factors associated with a history of non-fatal OD. METHODS: A sample of
      7085 Swedish criminal justice clients with alcohol or drug misuse was assessed,
      using the Addiction Severity Index. Subjects reporting use of opioids during the
      30 days prior to incarceration were included (n=1113). Relevant variables of
      misuse pattern, heredity, psychiatric symptoms and previous criminal charges were
      analysed in a logistic regression model. RESULTS: A history of non-fatal OD was
      reported by 55% (n=604). The estimated contribution to the variance in OD history
      was 25% for variables describing misuse pattern, compared to 10% for psychiatric
      symptoms, 8% for heredity, and 8% for previous criminal charges. The final model
      included the following variables: history of injection drug use (OR 3.28),
      history of heroin use (OR 2.87), history of suicide attempt (OR 1.92), history of
      tranquilliser use (OR 1.91), being born in Sweden or other Nordic countries (OR
      1.74), difficulty in controlling violent behaviour (OR 1.68), and paternal
      alcohol problems (OR 1.57). CONCLUSIONS: Suicide attempts and difficulty in
      controlling violent behaviour were associated with history of non-fatal OD,
      independent of variables of misuse pattern. This may indicate a possible
      association with impulse control disturbances, and may have clinical
      applications. Country of birth and heredity of alcohol problems also had some
      influence. As expected, severity of misuse most strongly contributed to history
      of non-fatal OD.

PMID- 18082337
TI  - Factors related to correctional facility incarceration among active injection
      drug users in Baltimore, MD.
AB  - AIM: We investigated the moderating effect of impulse control on the association
      between drug use and incarceration among active injection drug users (IDU).
      METHODS: The study sample consisted of 282 IDUs aged 15-50 years from the
      Baltimore metropolitan region who reported injection drug use within the past 6
      months and indicated that heroin or speedball was their drug of choice. Impulse
      control was measured using commission error standardized scores from the Test of
      Variables of Attention (TOVA). Incarceration was obtained using self-reported
      lifetime history of incarceration in correctional facilities. RESULTS: Findings
      indicated that impulse control moderated the association between years of
      injection drug use and incarceration in correctional facilities adjusting for
      ethnicity, gender, estimated pre-morbid intelligence, and age of first injection
      use. Specifically, among individuals who were intact in impulse control, four or
      more years of injection drug use was associated with incarceration (AOR=4.97, 95%
      CI: 2.02-12.23). This finding was not observed among individuals with impaired
      impulse control (AOR=0.57, 95% CI: 0.10-3.23). Furthermore, impulse control
      moderated the association between regular cocaine use and incarceration. Among
      individuals who had a history of cocaine use, individuals with low impulse
      control but not impaired were more likely to have reported time in a correctional
      facility (AOR=6.28, 95% CI: 1.68-23.60). There was no association among
      individuals with impaired or intact impulse control. CONCLUSION: Results
      highlight the importance of considering cognitive measures of impulse control in
      addressing negative outcomes associated with drug use.

PMID- 18082339
TI  - A systematic method for mapping multiple loci: an application to construct a
      genetic network for rheumatoid arthritis.
AB  - The advent of high-throughput single nucleotide polymorphisms (SNPs) omics
      technologies has brought tremendous genetic data. Systematic evaluation of the
      genome-wide SNPs is expected to provide breakthroughs in the understanding of
      complex diseases. In this study, we developed a new systematic method for mapping
      multiple loci and applied the proposed method to construct a genetic network for
      rheumatoid arthritis (RA) via analysis of 746 multiplex families genotyped with
      more than five thousands of genome-wide SNPs. We successfully identified 41
      significant SNPs relevant to RA, 25 associated genes and a number of important
      SNP-SNP interactions (SNP patterns). Many findings (loci, genes and interactions)
      have experimental support from previous studies while novel findings may define
      unknown genetic pathways for this complex disease. Finally, we constructed a
      genetic network by integrating the results from this analysis with the rapidly
      accumulated knowledge in biomedical domains, which gave us a more detailed
      insight onto the RA etiology. The results suggest that the proposed systematic
      method is powerful when applied to genome-wide association studies. Integrating
      the analysis of high-throughput SNP data with knowledge-based SNP functional
      annotation offers a promising way to reversely engineer the underlying genetic
      networks for complex human diseases.

PMID- 18082340
TI  - Epidemiological study of hepatitis E virus infection in European wild boars (Sus
      scrofa) in Spain.
AB  - Evidence of hepatitis E virus (HEV) infection in Spanish domestic pig has been
      reported and hence it was advisable to search for this zoonotic pathogen in wild
      boar populations. A total of 150 wild boar serum samples from eight geographic
      areas from South-Central Spain were used to investigate HEV infection in European
      wild boar (Sus scrofa) by means of serology and PCR and its distribution by age,
      region and management system. Anti-HEV IgG, IgM and IgA were determined by an in
      house ELISA. The overall seroprevalence was 42.7% (range 30.63-55.65%) and 19.6%
      (range 13.53-27.40%) of the animals tested positive for HEV RNA. Wild boar
      sequences were clustered within the genotype 3. This is the first description of
      HEV infection in Spanish wild boar and the results obtained may suggest a
      possible role of wild boar as a HEV reservoir for both domestic animals and
      humans.

PMID- 18082341
TI  - Melatonin-improved reproductive performance in sheep bred out of season.
AB  - The effects of melatonin implants on out-of-season breeding in New Zealand Romney
      composite ewes, was determined by comparison of reproductive performance in ewes
      treated with progesterone+equine chorionic gonadotrophin (eCG) (control; n=107),
      melatonin+progesterone+eCG (n=97) or melatonin+progesterone (n=96). Conception
      rates in melatonin+progesterone+eCG-treated ewes (67%) were higher than in the
      control ewes (P<0.01; 47%). Pregnancy rates were higher in
      melatonin+progesterone+eCG-treated ewes (55%; P<0.001) compared with the control
      ewes (40%). Fewer melatonin+progesterone-treated ewes displayed oestrus (14%;
      P<0.001) and subsequently became pregnant (6%). Oestrus rates in
      melatonin+progesterone-treated ewes (14%) were lower than both the
      melatonin+progesterone+eCG-treated (82%) and control ewes (86%; P<0.001), which
      were similar to each other. The number of foetuses per pregnant ewe was similar
      in all three treatment groups. Serum melatonin concentrations at Day -9 were
      higher in the ewes treated with melatonin and there was a large variation between
      individual ewes, but concentrations were similar for pregnant and nonpregnant
      ewes. The combination of higher conception rate and the trend for more lambs per
      pregnant ewes resulted in more lambs being born per ewe treated in
      melatonin+progesterone+eCG-treated ewes compared to the other two treatment
      groups. These results suggest that melatonin implants, in conjunction with
      administration of progesterone and eCG, may be suitable as a means of increasing
      the number of lambs born per ewe treated in an out-of-season breeding program in
      New Zealand sheep flocks while melatonin and progesterone is not.

PMID- 18082342
TI  - Uric acid: a surrogate of insulin resistance in older women.
AB  - OBJECTIVES: The relationship between serum uric acid (UA) and cardiovascular
      disease has been debated extensively and no conclusion has been reached yet. The
      main purpose of this study was to explore the sex-different relationship among
      insulin resistance, metabolic syndrome (MS) and hyperuricemia. METHODS: A
      community-based prospective study was conducted among people aged over 40 years
      in I-Lan County, Taiwan. A complete history taking, physical examination and
      laboratory tests were performed for each subject by the well-trained research
      staff. Insulin resistance was determined by the homeostasis model assessment
      (HOMA-IR). Serial comparisons were performed to evaluate the associations between
      MS, insulin resistance and hyperuricemia in both sexes. RESULTS: A total of 852
      subjects (mean age=64.6+/-11.3 years, 56.7% female) were enrolled. The prevalence
      of obesity, hyperuricemia, chronic kidney disease (CKD), insulin resistance and
      MS was 42.2, 31.2, 30.9, 36.0 and 47.5%, respectively. Subjects with MS were
      significantly older (63.4+/-10.0 years versus 60.4+/-12.4 years, P=0.019), higher
      in body mass index (BMI) (26.3+/-3.5 kg/m(2) versus 23.6+/-3.0 kg/m(2), P<0.001),
      serum UA (6.1+/-2.1mg/dl versus 5.5+/-1.7 mg/dl, P=0.003), HOMA-IR (2.7+/-3.4
      versus 1.0+/-0.8, P<0.001) and lower in glomerular filtration rate (GFR) (66.3+/
      17.7 ml/min/1.73 m(2) versus 72.0+/-15.2 ml/min/1.73 m(2), P=0.001). Male gender,
      CKD, BMI>23 kg/m(2) and insulin resistance were all independent risk factor for
      hyperuricemia with the covariate of age. When age and BMI were controlled,
      females had significantly higher prevalence of CKD and insulin resistance, but
      less hyperuricemia than males (P all<0.05). Adjusted for age, BMI and GFR,
      hyperuricemia and MS were both independent risk factors for insulin resistance in
      females (P=0.006, <0.001, respectively). In males, MS remained significantly
      associated with insulin resistance (P=0.002) but not hyperuricemia (P=0.813).
      When age, BMI and GFR were controlled, serum UA was positively related to HOMA-IR
      in females (gamma=0.117, P=0.012), but not in males (P=0.93). CONCLUSION: A
      positive association was identified between serum UA and insulin resistance in
      older women but not in men. Studies related to insulin resistance may be needed
      when hyperuricemia was identified in older women.

PMID- 18082343
TI  - Effective gene delivery with novel liposomal bubbles and ultrasonic destruction
      technology.
AB  - From the viewpoint of safety, non-viral vector systems represent an attractive
      gene delivery system for gene therapy. However, the transfection efficiency of
      non-viral vectors in vivo is generally very low. Previously, it was reported that
      microbubbles, utilized as imaging agents for diagnostic echocardiography, could
      promote gene delivery into cells when combined with ultrasound exposure. We
      therefore developed novel liposomal bubbles (Bubble liposomes) containing the
      lipid nanobubbles of perfluoropropane which is used as ultrasound imaging agent.
      These Bubble liposomes were smaller in diameter than conventional microbubbles
      and induced cavitation upon exposure to ultrasound. These results suggested that
      cavitation of these Bubble liposomes could be an efficient approach for
      delivering plasmid DNA into cells. In addition, in in vivo gene delivery, the
      combination of Bubble liposomes and ultrasound provided more effective gene
      delivery than conventional lipofection methods, further suggesting that Bubble
      liposomes could be effective as a non-viral vector system in in vivo gene
      delivery. In this review, we discuss the characteristics of Bubble liposomes and
      their potential utility as a gene delivery tool in vitro and in vivo.

PMID- 18082344
TI  - Preparation and stabilization of nifedipine lipid nanoparticles.
AB  - Design methods of nanoparticle formulations are divided into a break-down method
      and a build-up method. Furthermore, the former is further divided into dry and
      wet processes. For drug nanoparticle preparations, the wet process is generally
      employed, and organic solvents are used in most formulations. In this study, we
      investigated the preparation of nifedipine (NI) nanoparticles without using any
      organic solvent. NI nanoparticles with a mean particle size of approximately 50
      nm could be prepared without organic solvent by a combination of roll mixing and
      high-pressure homogenization. The X-ray diffraction peak of the sample prepared
      by roll mixing was present at an identical position (2theta) to that of NI
      crystals, showing that no peak shift was induced by interaction with lipid. These
      findings clarified that most NI remained as crystals in lipid. To maintain the
      particle size of the nanoparticles in suspension for a long time, a method of
      adding gelatin powder to the NI-lipid nanoparticle suspension, dissolving the
      mixture by heating, and then solidifying by cooling was investigated. The mean
      particle size of the sample was about 55 nm, and that after heat-liquefaction of
      the NI-lipid nanoparticle suspension gelated at 5 degrees C for 24h was also
      about 55 nm, showing that the nanoparticle condition was retained.

PMID- 18082345
TI  - Albumin-conjugated PEG liposome enhances tumor distribution of liposomal
      doxorubicin in rats.
AB  - To evaluate the effect of coupling of recombinant human serum albumin (rHSA) onto
      the surface of poly(ethylene glycol)-modified liposome (PEG liposome) on the in
      vivo disposition characteristics of liposomal doxorubicin (DXR), the
      pharmacokinetics and tissue distribution of DXR were evaluated after intravenous
      administration of rHSA-modified PEG (rHSA/PEG) liposomal DXR into tumor-bearing
      rats. rHSA/PEG liposome prepared using a hetero-bifunctional cross-linker, N
      succinimidyl 3-(2-pyridyldithio) propionate (SPDP), efficiently encapsulated DXR
      (over 95%). rHSA/PEG liposomal DXR showed longer blood-circulating property than
      PEG liposomal DXR and the hepatic and splenic clearances of rHSA/PEG liposomal
      DXR were significantly smaller than those of PEG liposomal DXR. It was also
      demonstrated that the disposition of DXR to the heart, one of the organs for DXR
      related side-effects, was significantly smaller than free DXR. Furthermore, the
      tumor accumulation of rHSA/PEG liposomal DXR was significantly larger than that
      of PEG liposomal DXR. The "therapeutic index", a criterion for therapeutic
      outcome, for rHSA/PEG liposomal DXR was significantly higher than PEG liposomal
      DXR. These results clearly indicate that rHSA-conjugation onto the surface of PEG
      liposome would be a useful approach to increase the effectiveness and safety of
      PEG liposomal DXR.

PMID- 18082346
TI  - The role of spatial location in auditory search.
AB  - The majority of research findings to date indicate that spatial cues play a minor
      role in enhancing listeners' ability to parse and detect a sound of interest when
      it is presented in a complex auditory scene comprising multiple simultaneous
      sounds. Frequency and temporal differences between sound streams provide more
      reliable cues for scene analysis as well as for directing attention to relevant
      auditory 'objects' in complex displays. The present study used naturalistic
      sounds with varying spectro-temporal profiles to examine whether spatial
      separation of sound sources can enhance target detection in an auditory search
      paradigm. The arrays of sounds were presented in virtual auditory space over
      headphones. The results of Experiment 1 suggest that target detection is enhanced
      when sound sources are spatially separated relative to when they are presented at
      the same location. Experiment 2 demonstrated that this effect is most prominent
      within the first 250 ms of exposure to the array of sounds. These findings
      suggest that spatial cues may be effective for enhancing early processes such as
      stream segregation, rather than simply directing attention to objects that have
      already been segmented.

PMID- 18082347
TI  - Origin of suppression of otoacoustic emissions evoked by two-tone bursts.
AB  - Otoacoustic emission (OAE) data recorded for tone bursts presented separately and
      as a two-tone burst complex, that had been reported previously [Yoshikawa, H.,
      Smurzynski, J., Probst R., 2000. Suppression of tone burst evoked otoacoustic
      emissions in relation to frequency separation. Hear. Res. 148, 95-106], were re
      processed using the method of adaptive approximations by matching pursuit (MP).
      Two types of stimuli were applied to record tone burst OAEs (TBOAEs): (a) cosine
      windowed tone bursts of 5-ms duration with center frequencies of 1, 1.5, 2 and
      3kHz, (b) complex stimuli consisting of a digital addition of the 1-kHz tone
      burst together with either the 1.5-, 2- or 3-kHz tone burst. The MP method
      allowed decomposition of signals into waveforms of defined frequency, latency,
      time span, and amplitude. This approach provided a high time-frequency (t-f)
      resolution and identified patterns of resonance modes that were characteristic
      for TBOAEs recorded in each individual ear. Individual responses to single-tone
      bursts were processed off-line to form 'sum of singles' responses. The results
      confirmed linear superposition behavior for a frequency separation of two-tone
      bursts of 2kHz (the 1-kHz and 3-kHz condition). For the 1, 1.5-kHz condition, the
      MP results revealed the existence of closely positioned resonance modes
      associated with responses recorded individually with the stimuli differing in
      frequency by 500Hz. Then, the differences between t-f distributions calculated
      for dual (two-tone bursts) and sum-of-singles conditions exhibited mutual
      suppression of resonance modes common to both stimuli. The degree of attenuation
      depended on the individual pattern of characteristic resonance modes, i.e.,
      suppression occurred when two resonant modes excited by both stimuli overlapped.
      It was postulated that the suppression observed in case of dual stimuli with
      closely-spaced components is due to mutual attenuation of the overlapping
      resonance modes.

PMID- 18082348
TI  - Alfa-glucosidase-inhibiting activity of some Mexican plants used in the treatment
      of type 2 diabetes.
AB  - Type 2 diabetes is an endocrine disease, which accounts for 9% of deaths
      worldwide. The aim of oral therapy is to reach normoglycemia to prevent later
      complications. Among glucose-lowering medications, alpha-glucosidase inhibitors
      delay the absorption of ingested carbohydrates, reducing the postprandial glucose
      and insulin peaks. In the present study, we tested the butanolic extracts of four
      Mexican plants with respect to their alpha-glucosidase inhibition activity,
      without excluding other possible mechanisms of action. The plants Cecropia
      obtusifolia Bertol., Equisetum myriochaetum Schlecht & Cham, Acosmium panamense
      (Benth.) Yacolev and Malmea depressa (Baill) R.E. Fries are used in traditional
      medicine to treat type 2 diabetes. In previous studies, we have demonstrated
      these plants' hypoglycemic activity and determined the phytochemical composition
      of their extracts. Our results in n-STZ diabetic rats loaded with maltose showed
      that Malmea and Acosmium extracts decreased plasma glucose significantly from 30
      min on resembling the effect of acarbose. Cecropia extract produced the highest
      reduction of plasma glucose, and at 90 min, the glucose level was lower than the
      fasting level, which suggests another mechanism of action. Equisetum did not
      exert any effect. In vitro assays of alpha-glucosidase activity showed an IC(50)
      of 14 microg/ml for Cecropia, 21 microg/ml for Malmea, and 109 microg/ml for
      Acosmium, which were lower than that of acarbose (128 microg/ml). Equisetum did
      not show any significant effect on this assay, either. These results contribute
      to understand the mechanism of action of these plants on glucose metabolism.

PMID- 18082349
TI  - Current concepts in maxillofacial imaging.
AB  - A review of state-of-the-art maxillofacial imaging is presented. Current imaging
      techniques include intra-oral radiographs, dental panoramic tomography,
      multidetector helical computed tomography, cone-beam computed tomography (CBCT)
      and magnetic resonance imaging (MRI). The commonest conditions encountered in
      clinical radiological practice are reviewed, including maxillofacial deformities,
      complicated dental impactions, maxillofacial trauma, jaw lesions (cysts,
      neoplasms, fibro-osseous lesions (FOLs) and infections), and temporomandibular
      joint pathology. Pre-operative assessment for dental implant placement is also
      briefly reviewed.

PMID- 18082350
TI  - Determination of nimodipine in human plasma by ultra performance liquid
      chromatography-tandem mass spectrometry and pharmacokinetic application.
AB  - A fast and sensitive ultra performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS/MS) method was developed for the determination and
      pharmacokinetic study of nimodipine in human plasma. With nitrendipine as the
      internal standard, sample pretreatment involved one-step extraction with diethyl
      ether of 0.5 ml plasma. The separation was carried out on an ACQUITY UPLC BEH
      C(18) column (50 mm x 2.1 mm, i.d., 1.7 microm) with water and acetonitrile (both
      containing 0.1% formic acid) as the mobile phase under gradient conditions at a
      flow rate of 0.35 ml/min. The detection was performed on a triple quadrupole
      tandem mass spectrometer by multiple reaction monitoring (MRM) mode via
      electrospray ionization (ESI) source. The standard curves were linear (r(2)> or
      =0.99) over the concentration range of 0.20-100 ng/ml with a limit of
      quantification (LLOQ) of 0.20 ng/ml. The intra- and inter-day precision (R.S.D.)
      values were below 14% and the accuracy (relative error R.E.) was ranged from 
      2.2% to 7.7% at all three quality control (QC) levels. The method herein
      described was superior to previous methods and successfully applied to the
      pharmacokinetic study of nimodipine tablets in healthy male volunteers after oral
      administration.

PMID- 18082351
TI  - FIA determination of ascorbic acid at low potential using a ruthenium oxide
      hexacyanoferrate modified carbon electrode.
AB  - The anodic oxidation of ascorbic acid on a ruthenium oxide hexacyanoferrate
      modified electrode was characterized by cyclic voltammetry. On this modified
      surface, the electrocatalytic process allows the determination of ascorbic acid
      to be performed at 0.0 V and pH 6.9 with a limit of detection of 2.2 microM in a
      flow injection configuration. Under this experimental condition, no interference
      from glucose, nitrite and uric acid was noticed. Lower detection limit values
      were obtained by measuring flow injection analysis (FIA) responses at 0.4V (0.14
      microM), but a concurrent loss of selectivity is expected at this more positive
      potential. Under optimal FIA operating conditions, the linear response of the
      method was extended up to 1 mM ascorbic acid. The repeatability of the method for
      injections of a 1.0 mM ascorbic acid solution was 2.0% (n=10). The usefulness of
      the method was demonstrated by an addition-recovery experiment with urine samples
      and the recovered values were in the 98-104% range.

PMID- 18082352
TI  - A quality by design approach to impurity method development for atomoxetine
      hydrochloride (LY139603).
AB  - The development of an ion-pairing HPLC method and associated system suitability
      parameters for the analysis of atomoxetine hydrochloride (LY139603 HCl) using a
      quality by design approach is described. Potential method conditions were
      evaluated for their ability to meet design requirements and statistically
      designed experiments were used to optimize conditions and demonstrate method
      robustness for the separation of atomoxetine and impurities. The separation of
      two early eluting impurities, phenyl methylaminopropanol (PMAP (+/-)3-methylamino
      1-phenylpropanol) and mandelic acid is correlated to the separation of other
      impurities that elute near the main sample component and the resolution of this
      peak pair is used as a system suitability test without the need for impurity
      reference standards.

PMID- 18082353
TI  - Sunitinib in the management of gastrointestinal stromal tumours (GISTs).
AB  - AIMS: Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of
      the gut with a 5-year survival of approximately 50%. Surgery remains the
      treatment of choice in resectable disease, with conventional chemotherapy largely
      ineffective. Over 90% of GIST possesses mutations in the c-KIT oncogene,
      producing an overactive tyrosine kinase, which may be driving the malignant
      process. Imatinib inhibits the aberrant tyrosine kinase and imatinib therapy in
      metastatic disease has shown significant clinical benefit. However, resistance
      typically develops within 2 years, with the need for further therapy. This
      article aims to introduce the reader to a new development in cancer therapeutics.
      METHODS: A literature search was performed using the MEDLINE database to identify
      publications relevant to the review. References within these articles were used
      to expand the search. Abstracts from recent ASCO symposia were hand searched for
      relevant articles. FINDINGS: Sunitinib (SU11248) is a novel multi-targeted
      tyrosine kinase inhibitor with activity not only against the receptor tyrosine
      kinase product of c-KIT but also other cell-signalling pathways that may be
      relevant in GIST; FLT3, platelet-derived growth receptor (PDGFR) and vascular
      endothelial growth factor receptor (VEGFR). Two Phase II trials and one Phase III
      trial have investigated the activity of sunitinib against imatinib-resistant
      GIST. Early results showed significant benefits in time to disease progression
      that led to licensing of the drug in America and more recently in Europe. A Phase
      III trial comparing dose-increased imatinib and sunitinib in progressed GIST is
      currently planned. CONCLUSIONS: Initial clinical results with sunitinib are
      promising and suggest a future role. Further studies are needed before sunitinib
      can be recommended for the routine treatment of imatinib-refractory GIST.

PMID- 18082354
TI  - [Update on the consensus conference on difficult airway management: what about
      the future?].

PMID- 18082355
TI  - [Impact of mobile intensive care units on treating stroke within the 3-hour time
      window in a semi-rural area].
AB  - OBJECTIVES: We tested the hypothesis that calling emergency medical services
      ("15", French equivalent of 911 or 999 calls) and response by a mobile intensive
      care unit staffed by emergency physicians (MICU) reduces the time to treatment to
      within the 3-hour time window required for administration of recombinant tissue
      plasminogen activator. METHODS: This study compared the time from symptom onset
      to admission (prehospital time), from admission to treatment (imaging and
      treatment delays, hospital time), and total time from symptom onset to treatment
      in an observational cohort of 53 consecutive patients, according to how they
      reached the hospital (Group 1: MICU and group 2: standard emergency ambulance
      dispatched by EMS center [2a] or direct admission [2b]). RESULTS: The study
      included 52 patients (1 was excluded because hospitalized at the time of the
      stroke): 27 (51.9%) in group 1, 16 (30.8%) in group 2a, and 9 (17.3%) in group
      2b. Calling "15" shortened total home-to-needle time by 24 minutes (p=0.034). The
      mean total time was not significantly shorter in group 1 (152 versus 162 min;
      p=0.27) but MICUs were used for patients farther away (mean distance 25 versus 11
      km; p=0.02). The average prehospital time was thus higher in group 1 (86 versus
      69 min; p=0.044), but was compensated by a reduction in the average hospital time
      (66 versus 93 min; p=0.0001), due mainly to shorter waits for imaging (22 versus
      45 min; p=0.0001). CONCLUSION: Calling the emergency services number reduces mean
      total time. MICUs were associated with a longer prehospital time, mainly due to
      greater distances, but they facilitated in-hospital management.

PMID- 18082356
TI  - [Fever as a prognostic factor for heat stroke].
AB  - OBJECTIVES: Classic heatstroke that is, due to very hot weather, rare in Europe.
      Its clinical characteristics and course in temperate zones are not well known.
      The objective of this study was to assess the influence of initial fever on
      prognosis in heatstroke. METHODS: All patients admitted through the emergency
      department from 8-13 August 2003 for heatstroke (defined by fever > or = 40
      degrees C, with neurologic symptoms in the absence of sepsis) were included in
      the study. Patients' clinical and laboratory indicators were recorded at
      admission. Follow-up took place at D28 and 1 year. The influence of fever on
      survival was assessed with the Kaplan-Meier method. RESULTS: During the study
      period, 63 patients, aged 78+/-9 years, were admitted for heatstroke, with a SAPS
      II (Simplified Acute Physiology Score) of 61+/-24. Core body temperature was
      41.4+/-1.2 degrees C. Mortality was 59% at D28 and 67% at 1 year. Prognosis was
      influenced from admission by temperature, with a higher probability of survival
      for patients with temperature < 41 degrees C, compared with those whose
      temperature > or = 41 degrees C (log-rank test: p<0.001). DISCUSSION: Prognosis
      is poor for classic heatstroke. Rapid temperature reduction, especially when it
      exceeds > 41 degrees C, must be considered a priority. Fever > or = 41 degrees C
      at admission for heatstroke is a poor prognostic factor that is simple to
      identify and may modify treatment strategies in the future.

PMID- 18082357
TI  - The symptom experience of oncology outpatients has a different impact on quality
      of-life outcomes.
AB  - The aims of this replication study were to determine if subgroups of oncology
      outpatients receiving active treatment could be identified based on their
      experience with the symptoms of fatigue, sleep disturbance, depression, and pain;
      whether patients in these subgroups differed on selected demographic, disease,
      and treatment characteristics; and if patients in these subgroups differed on
      functional status and quality of life (QOL). A convenience sample of 228 oncology
      outpatients was recruited from seven outpatient settings in Israel. Patients
      completed a demographic questionnaire, a Karnofsky Performance Status score, the
      Multidimensional Quality of Life Scale-Cancer, the Lee Fatigue Scale, the General
      Sleep Disturbance Scale, the Center for Epidemiological Studies-Depression Scale,
      and a numeric rating scale of worst pain intensity. Cluster analysis was used to
      identify the patient subgroups based on their symptom experience. Four relatively
      distinct patient subgroups were identified based on their experiences with the
      above symptoms (i.e., low levels of all four symptoms (32.9%), low levels of pain
      and high levels of fatigue (18.0%), high levels of pain and moderate levels of
      fatigue (42.5%), and high levels of all four symptoms (6.6%). No differences were
      found among the four subgroups on any demographic, disease, or treatment
      characteristics. The subgroup of patients who reported high levels of all four
      symptoms reported the worst functional status and poorest QOL. In conclusion,
      differences in the symptom experience of oncology outpatients suggest that
      patients may harbor different phenotypic characteristics (e.g., environmental or
      physiologic) or genetic determinants for experiencing symptoms that are
      independent of demographic, disease, and treatment characteristics.

PMID- 18082358
TI  - Plasma interleukin-6 and fatigue in terminally ill cancer patients.
AB  - Fatigue is one of the most distressing symptoms among terminally ill cancer
      patients. However, no effective intervention has been established. Several
      studies have suggested the role of cytokines in fatigue in cancer patients
      receiving anti-cancer treatment, patients with metastatic cancer, and cancer
      survivors, but not in terminally ill cancer patients. In the present study, the
      potential association between fatigue and plasma interleukin-6 (IL-6) was
      examined in 46 terminally ill cancer patients (median survival: 64.5 days) who
      received neither steroids nor nonsteroidal anti-inflammatory drugs. Fatigue was
      evaluated by the Cancer Fatigue Scale (CFS), which consists of multiple
      dimensions of fatigue, such as Physical, Affective, and Cognitive subscales.
      Plasma IL-6 levels were measured using an enzyme-linked immunosorbent assay and
      were compared between patients with and without "clinical fatigue" as defined by
      the total score of the CFS. Additionally, associations between each of the CFS
      scores and IL-6 levels were examined. As a result, the IL-6 level in patients
      with clinical fatigue (n=27 [59%]; mean, SD, median, and range: 37.1, 46.4, 17.1,
      and 3.7-182.5pg/ml, respectively) was significantly higher than those without
      clinical fatigue (n=19 [41%]; mean, SD, median, range: 14.3, 12.2, 8.0, and 2.8
      45.0pg/ml, respectively) (P=0.02). The IL-6 level significantly correlated with
      the Physical subscale score (r=0.35, P=0.02), but not with other subscale scores.
      In conclusion, IL-6 may play a role in fatigue, especially in the physical
      dimension, in terminally ill cancer patients. The results of the present study
      provide information to develop a new treatment strategy for cancer fatigue in
      terminally ill cancer patients.

PMID- 18082359
TI  - Use of the palliative outcome scale in Argentina: a cross-cultural adaptation and
      validation study.
AB  - Although measuring outcomes is essential to ensuring palliative care
      effectiveness, there is an absence of properly validated measures in many
      countries. We undertook a cross-cultural adaptation and validation of the
      Palliative Outcome Scale (POS) into a Spanish (Argentina) language and cultural
      context. The methodology used a sequence of phases: 1) verification of conceptual
      equivalence (literature review, professional interviews, and patient focus
      groups); 2) multiple translations; 3) committee review; and 4) field testing.
      Psychometric analysis entailed evaluation of quantitative content validity,
      construct validity, staff and patients' ratings comparison, internal consistency,
      test-retest reliability, and responsiveness to change. Conceptual equivalence was
      achieved. Multiple changes were introduced after the translations and field
      testing in 65 patients and 20 professionals. Content validity was high for all
      but one item. Construct validity against a validated quality-of-life measure
      (European Organization for Research and Treatment of Cancer Quality of Life C-30)
      was confirmed (rho=0.74, P<0.0005). There was acceptable agreement between staff
      and patients (Cohen's weighted kappa >0.3) for 5/10, 8/10, and 6/9 items at each
      of three time-point evaluations and good correlation for all but one item
      (Spearman coefficient >0.7). Internal consistency was acceptable (Cronbach's
      alpha=0.68-0.69 and 0.66-0.73) for patient and staff ratings, respectively, and
      test-retest reliability showed very high agreement for every item (>0.80). The
      Argentine POS showed adequate responsiveness to change, although significant
      difference was reached for only 3 out of 10 items for patients and staff,
      respectively. Completion of the POS did not take more than 12 and 6 minutes for
      patients and staff, respectively. This study indicates that the Argentine POS is
      a valid and reliable measure of palliative care outcomes with advanced cancer
      patients.

PMID- 18082360
TI  - Protocatechuic acid inhibits apoptosis by mitochondrial dysfunction in rotenone
      induced PC12 cells.
AB  - Protocatechuic acid (PCA), a phenolic compound isolated from the kernels of
      Alpinia (A.) oxyphylla, showed the significant neuroprotective effects on
      hydrogen peroxide (H2O2) or MPP+-induced apoptosis in cultured PC12 cells.
      However, the mechanism how PCA suppresses rotenone-induced neurotoxicity in
      cultured PC12 cells remains unclear. In this study, we investigated the
      protective effects of PCA in PC12 cells exposed to rotenone as an in vitro model
      of mitochondrial dysfunction and apoptotic cell death. The apoptosis in rotenone
      induced PC12 cells was accompanied by the loss of mitochondrial membrane
      potential, the formation of reactive oxygen species (ROS), the total glutathione
      depletion, activation of caspase-3 and down-regulation of Bcl-2. In contrast, PCA
      markedly attenuated the above-mentioned mitochondrial dysfunction in a dose
      dependent manner. Taken together, these results suggest that treatment of PC12
      cells with PCA can block rotenone-induced apoptosis via ameliorating the
      mitochondrial dysfunction.

PMID- 18082361
TI  - Purification and characterization of approximately 35 kDa antioxidant protein
      from curry leaves (Murraya koenigii L.).
AB  - Curry leaves (Murraya koenigii L. Spreng, Rutaceae) is an herbal species used in
      traditional medicine in eastern Asia. In this study, the antioxidant protein was
      purified by homogenization of curry leaves powder in Tris buffer, 65% ammonium
      sulphate precipitation and gel filtration on Sephadex G-75 column which resulted
      in three peaks (PI, PII and PIII). PII protein inhibited lipid peroxidation in
      human RBC ghost at 100 microg by 80%, whereas PI and PIII at 600 microg showed
      moderate antioxidant activity (40-50%). Homogeneity of PII was confirmed by
      rechromatographing on Sephadex G-75 and reverse phase HPLC. The antioxidant
      protein (PII) from curry leaves (APC) showed apparent molecular weight of 35 kDa
      by SDS-PAGE and MALDI/MS analysis. The protein nature of APC was established by
      the presence of amino acids and loss of antioxidant activity on heat and protease
      treatment. The APC at 0.8 microM inhibited lipoxygenase activity by 71%,
      effectively prevented diene, triene and tetraene lipids formation at 3 microM,
      and scavenged about 85% hydroxyl and DPPH radicals at 150-fold lesser
      concentration compared to BHA and alpha-tocopherol (400 microM). In addition, APC
      reduced cytochrome c and ferric ion, chelated ferrous ion, and inhibited ferrous
      sulfate: ascorbate-induced fragmentation and sugar oxidation to 80-90%. Thus, the
      present study demonstrates the in vitro characterization of antioxidant protein
      from the curry leaves (M. koenigii L.).

PMID- 18082362
TI  - The Philadelphia Face Perception Battery.
AB  - The Philadelphia Face Perception Battery (PFPB) tests four aspects of face
      perception: discrimination of facial similarity, attractiveness, gender, and age.
      Calibration with 116 neurologically intact subjects yielded average performance
      of approximately 90%. Across subjects, there was a low correlation (<0.22) in
      performance between the tests (with the exception of the attractiveness and age
      discrimination tests) suggesting that the tests measure independent aspects of
      face perception. There were modest effects of subject demographic factors upon
      performance, and test-retest reliability scores (between 0.37 and 0.75) were
      comparable to other neuropsychological batteries. Modification of the stimuli to
      obscure internal facial features lowered performance on the age, gender, and
      attractiveness discrimination tests between 2 and 4 standard deviations. The
      clinical sensitivity of the battery was demonstrated by testing a patient with
      acquired prosopagnosia. She showed performance impairments of between 2 and 4
      standard deviations on all sub-tests. The PFPB is freely available for non
      commercial use.

PMID- 18082363
TI  - Coexpression, coregulation, and cofunctionality of neighboring genes in
      eukaryotic genomes.
AB  - Accumulating evidence indicates that gene order in eukaryotic genomes is not
      completely random and that genes with similar expression levels tend to be
      clustered within the same genomic neighborhoods. The mechanism behind these gene
      coexpression clusters is as yet unclear. In this article, plausible biochemical,
      genetic, evolutionary, and technological determinants of this pattern are briefly
      reviewed.

PMID- 18082364
TI  - Voice onset time in women as a function of oral contraceptive use.
AB  - Previous studies of the effect of hormonal changes across phases of the menstrual
      cycle on voice onset time (VOT) have not considered the variable of oral
      contraceptive use. The purpose of this study was to examine both the effects of
      menstrual cycle phase and that of oral contraceptive use on VOT. It was
      hypothesized that women taking oral contraceptives would exhibit smaller VOT
      differences across the phases of their menstrual cycles. The study was a
      prospective matched-group experimental design. Participants were 10 women who
      were on oral contraceptives and 10 who were not. The participants were recorded
      over two menstrual cycles, on the 10th and 20th day to evaluate their speech
      during the preovulation and premenstrual phases of their menstrual cycle.
      Participants produced 10 repetitions of the phrase "Speak ___ to me" containing
      the target syllables /bae/ and /pae/. Repeated measure ANOVAs revealed no
      significant differences in VOT between the two groups. Statistical results showed
      significant interactions between the menstrual cycle phase and the 2 recording
      months. It is possible that month-to-month differences in hormonal levels and
      other factors that can affect speech may have a greater effect on VOT than either
      the taking of oral contraceptives or the phase differences within a menstrual
      cycle.

PMID- 18082365
TI  - Formant characteristics of vowels produced by Mandarin esophageal speakers.
AB  - With the use of the pharyngoesophageal (PE) segment as the neoglottis in
      esophageal speakers, their voice quality becomes significantly different from
      that of laryngeal speakers. The present study investigated the characteristics of
      the vocal tract resonance in Mandarin esophageal speakers. The first three
      formant frequencies of vowels /a, epsilon, i, [see in text], u, y/ produced by
      seven superior esophageal and seven laryngeal speakers of Mandarin were obtained.
      For each formant, the formant frequencies measured from the medial 80% of the
      vowel portion were averaged, and data obtained from esophageal speakers were
      compared with that obtained from laryngeal speakers. The results indicated that
      esophageal speakers were associated with significantly higher formant frequencies
      (F(1), F(2), and F(3)) and a significantly diminished vowel space circumscribed
      by the three corner vowels /i/, /a/, and /u/ when compared with laryngeal
      speakers. The findings that formant frequency changes across vowels were
      systematic and similar for esophageal and laryngeal speakers are consistent with
      those previously reported in English. It can be concluded that vocal tract
      transmission has been changed in esophageal speakers of Mandarin after
      laryngectomy.

PMID- 18082366
TI  - Dynamic MRI of larynx and vocal fold vibrations in normal phonation.
AB  - Dynamic magnetic resonance imaging (MRI) of the larynx and vocal folds during
      phonation was used for measuring the vertical laryngeal movements and the glottal
      angle of the vocal folds opening and closing in dynamic phase. The data used in
      this analysis were taken on 10 healthy volunteers during maximal inspiration and
      the prolonged phonation of the vowels [i] (as in key), [a] (as in car), [u] (as
      in loop), and the consonant [sh] (as in ship). The results of our MRI data have
      demonstrated the difference of the vocal folds movement in relation to the vowel
      and consonant sounds, with a large glottal opening for [sh] and a narrow opening
      for [i] and [u], and the difference of the laryngeal position in relation to the
      vowels, with [a] and [u] having a lower larynx position than [i]. Imaging the
      larynx's positions and the vocal folds' vibrations is possible using dynamic MRI.
      This technique permits measurements of laryngeal structures and glottal
      parameters in dynamic function with multiplanar high-resolution imaging. Analysis
      of laryngeal activity and vocal folds' vibration may be helpful for the
      evaluation of the phonation function and for the understanding of the physiology
      of vocal production and voice modulation.

PMID- 18082368
TI  - Missed opportunity for larynx preservation? Failure to distinguish verrucous and
      squamous cell carcinoma on microlaryngoscopy and biopsy.
AB  - The current standard for stage III and selected stage IV squamous cell carcinoma
      of the larynx includes organ sparing concurrent chemoradiation therapy. Verrucous
      carcinoma is predominantly treated with surgery, including laryngectomy in
      selected cases. Expert and appropriate pathologic interpretation of verrucous
      carcinoma with an ample biopsy specimen of the larynx using microlaryngoscopy can
      differ from the final pathology (squamous cell carcinoma) in a laryngectomy
      specimen. This can potentially lead to a failed opportunity for larynx
      preservation. A 68-year-old African-American male presented with a chief
      complaint of airway obstruction from a massive obstructing laryngeal tumor. This
      patient was initially treated with operative microlaryngoscopy and debulking of
      the laryngeal neoplasm. Computed tomography scan was not interpreted for
      cartilaginous invasion. Final pathological interpretation of this
      microlaryngoscopy and biopsy specimen included an "outside the institution"
      expert second opinion and that interpretation was consistent with verrucous
      carcinoma. Multidisciplinary head and neck oncology team recommendation was total
      laryngectomy. Final pathology report of the laryngectomy specimen revealed
      squamous cell carcinoma with extension through cartilage and anterior soft tissue
      extension. Expert and appropriate interpretation of an ample biopsy specimen by
      microlaryngoscopy can result in failure to distinguish verrucous from squamous
      cell carcinoma, potentially leading to missed opportunities for larynx
      preservation. In this case, cartilage invasion of a massive larynx squamous cell
      carcinoma made laryngectomy a reasonable therapeutic option.

PMID- 18082367
TI  - Transtheoretical model of health behavior change applied to voice therapy.
AB  - Studies of patient adherence to health behavior programs, such as physical
      exercise, smoking cessation, and diet, have resulted in the formulation and
      validation of the Transtheoretical Model (TTM) of behavior change. Although
      widely accepted as a guide for the development of health behavior interventions,
      this model has not been applied to vocal rehabilitation. Because resolution of
      vocal difficulties frequently depends on a patient's ability to make changes in
      vocal and health behaviors, the TTM may be a useful way to conceptualize voice
      behavior change processes, including the patient's readiness for change. The
      purpose of this paper is to apply the TTM to the voice therapy process to: (1)
      provide an organizing framework for understanding of behavior change in voice
      therapy, (2) explain how treatment adherence problems can arise, and (3) provide
      broad strategies to improve treatment adherence. Given the significant role of
      treatment adherence in treatment outcome, considering readiness for behavior
      change should be taken into account when planning treatment. Principles of health
      behavior change can aid speech pathologists in such understanding and estimating
      readiness for voice therapy.

PMID- 18082369
TI  - Vocal characteristics in children with attention deficit hyperactivity disorder.
AB  - The aim of this study was to evaluate vocal changes in patients with attention
      deficit hyperactivity disorder (ADHD). Nineteen children diagnosed to have ADHD
      according to the Diagnostic and Statistical Manual of Mental Disorders criteria
      and 19 controls were enrolled in this study. They underwent vocal perceptual
      evaluation and acoustic analysis. Hoarseness, breathiness, strain, and loudness
      were graded on a scale of 0-3. The following acoustic parameters were recorded:
      Fundamental frequency, Shimmer, Relative average perturbation, Noise-to-Harmony
      ratio, Voice Turbulence Index, and Habitual pitch. Children with ADHD were
      perceived to have significantly more hoarseness, breathiness, and straining in
      their voice. They were also louder compared to controls. There were no
      significant changes in the acoustic parameters except for the Fundamental
      frequency, which was lower in the ADHD group. The vocal behavior in children with
      ADHD is different than controls. Early diagnosis of such behavior in this group
      of children is important.

PMID- 18082370
TI  - Pain perception of children undergoing nasendoscopy for investigation of voice
      and resonance disorders.
AB  - The primary objective of this descriptive and correlational study was to
      determine the level of pain and discomfort perceived by children undergoing
      nasendoscopy for investigation of voice and resonance disorders. The secondary
      objective was to explore whether gender, age, previous experience of painful or
      distressing medical procedures, and previous experience of nasendoscopy
      influenced the perception of pain during nasendoscopy. Twenty-three children self
      reported the degree of pain perceived during nasendoscopy using the Wong-Baker
      Faces Pain Rating Scale. Parents also used this scale to rate their child's
      perceived pain. Otolaryngologists and speech pathologists rated the intensity and
      frequency of observed pain-related behaviors using the Child-Adult Medical
      Procedure Interaction Scale-Revised and the Procedure Behavior Checklist.
      Children perceived the procedure, on average, to be moderately painful, as did
      their parents. Only two children reported perceiving no pain during the
      procedure. The most frequently observed pain-related behaviors were muscle
      tension (86.96%), physical resistance (69.57%), requiring physical restraint
      (60.87%), crying (43.48%), and expressions of verbal pain (39.13%). No
      significant correlations were found between self-reported pain or observed pain
      and the variables of age, gender, previous experience of nasendoscopy, and
      previous experience of painful or distressing medical procedures, although
      children aged 4-7 years reported significantly more pain than children aged 8-18
      years. Most children perceive nasendoscopy to be painful to some degree. This
      perceived pain occurred in conjunction with several observable pain-related
      behaviors that have the potential to interfere with the success of the procedure.

PMID- 18082371
TI  - A concept of volume rendering guided search process to analyze medical data set.
AB  - This paper firstly presents an approach of parallel coordinates based parameter
      control panel (PCP). The PCP is used to control parameters of focal region-based
      volume rendering (FRVR) during data analysis. It uses a parallel coordinates
      style interface. Different rendering parameters represented with nodes on each
      axis, and renditions based on related parameters are connected using polylines to
      show dependencies between renditions and parameters. Based on the PCP, a concept
      of volume rendering guided search process is proposed. The search pipeline is
      divided into four phases. Different parameters of FRVR are recorded and modulated
      in the PCP during search phases. The concept shows that volume visualization
      could play the role of guiding a search process in the rendition space to help
      users to efficiently find local structures of interest. The usability of the
      proposed approach is evaluated to show its effectiveness.

PMID- 18082372
TI  - Surface modeling--uncertainty estimation and visualization.
AB  - The work presents a method of determining uncertainty of surface-based models
      that are reconstructed fragments of a human body built on the basis of slice
      images received from computed tomography CT or magnetic resonance imaging MRI. An
      analysis of geometric structure of the models has been carried out determining
      features, such as local inclination angle of the normal to the surface relative
      to the direction of scanning, and local radius of curvature. These features,
      together with the distance between slice images, have the largest influence on
      accuracy of the reconstructed surface-based models. A model of uncertainty has
      been determined by comparing properly selected virtual anatomical models and
      their spatial reconstructions. The estimated uncertainty model has then been
      employed to determine local errors in geometric structure of surface-based
      models. A quality visualisation of the errors in the geometric model has been
      presented in the form of a colour scale, and a quantity visualisation in the form
      of a ribbon, whose width is proportional to the uncertainty model.

PMID- 18082373
TI  - In vitro anti-Gram-positive and antistaphylococcal biofilm activity of newly
      halogenated pyrroles related to pyrrolomycins.

PMID- 18082374
TI  - Isolation and characterisation of two novel coliphages with high potential to
      control antibiotic-resistant pathogenic Escherichia coli (EHEC and EPEC).
AB  - Two newly isolated virulent coliphages (MVBS and MVSS) showed ability to lyse
      (form plaque on) a high percentage of pathogenic Escherichia coli strains of
      various serotypes and origins (292/310; 94.2%), whilst displaying low lytic
      (plaque-forming) capacity on non-pathogenic ECOR strains (MVBS and MVSS lysed
      10/72 (13.9%) and 15/72 (20.8%) strains, respectively). In comparison, a higher
      percentage (196/310, 63.2%) of tested isolates exhibited resistance to a broad
      range of antibiotics. It was also observed that, in contrast to antibiotics,
      phage treatment did not induce Shiga toxin production. These findings suggest
      that the newly isolated bacteriophages have potential for biocontrol and as
      therapeutic agents for pathogenic E. coli (EHEC and EPEC) strains.

PMID- 18082375
TI  - In vitro synergism between rokitamycin and co-trimoxazole against Streptococcus
      pyogenes, Streptococcus pneumoniae and staphylococci.

PMID- 18082376
TI  - First report of metronidazole-induced QT interval prolongation.

PMID- 18082377
TI  - Smoking in relation to anxiety and depression: evidence from a large population
      survey: the HUNT study.
AB  - Smoking is reported to be associated with depression and anxiety. The present
      study (a) examines these associations taking comorbidity into account, (b)
      investigates possible confounders, (c) examines how former smokers compared to
      current and never-smokers in terms of anxiety and depression, and if anxiety and
      depression decline by time since cessation. Participants (66%) aged 20-89 years
      in a population-based health survey (N=60,814) were screened employing the HADS.
      (a) The association with smoking was strongest in comorbid anxiety depression,
      followed by anxiety, and only marginal in depression. Associations were stronger
      in females and younger participants. (b) Variables partly accounting for the
      association comprised somatic symptoms, socio-demographics, alcohol problems, and
      low physical activity. (c) Anxiety and depression were most common in current
      smokers, followed by quitters, and then never-smokers. No decline in anxiety or
      depression was found with time since cessation. Previous studies of associations
      between depression and smoking might have overestimated the association when
      ignoring comorbid anxiety.

PMID- 18082378
TI  - Finding of abnormal scanning behavior in the Span of Apprehension task in
      schizophrenia but diagnostic non-specificity of sum scores.
AB  - Deficits in the Span of Apprehension (SOA) task have been discussed
      controversially as a trait marker of schizophrenia. The task was administered to
      47 schizophrenia and 48 depressed patients as well as to 46 controls. Results
      indicate a non-specificity of the SOA sum scores but differential abnormalities
      in spatial visual processing.

PMID- 18082379
TI  - A descriptive case-register study of delusional disorder.
AB  - OBJECTIVE: A few empirically based studies' data on delusional disorder (DD)
      exist. We aim to describe sociodemographic and clinical correlates of DD and to
      identify clinical profiles associated to DD and its subtypes. METHODS: This is a
      case-register study based on all those subjects attending community mental health
      services within a geographically well-defined area. Four hundred and sixty-seven
      patients had been diagnosed as DD cases at psychiatric services serving a
      catchment area of some 607,494 inhabitants living in South Barcelona (Spain)
      during a three-year period (2001-2003). A thorough systematic review of
      computerised medical records was used to establish DSM-IV diagnosis, rendering a
      valid sample of 370 patients who fulfilled DSM-IV criteria for DD. Independent
      variables gathered include sociodemographic data, family and personal psychiatric
      history, and comorbid diagnoses on all DSM-IV axes (including GAF). We used
      descriptive and univariate statistical methods to explore sample frequencies and
      correlates across DD types. RESULTS: The mean age of the patients was 55 years
      and the sample had a mean GAF score of 51 suggesting a poor functionality; 56.5%
      of the patients were female. The most frequent DD types were persecutory (48%),
      jealous (11%), mixed (11%) and somatic (5%), whilst 23% qualified for the NOS
      type. Most frequent symptoms identified were self-reference (40%), irritability
      (30%), depressive mood (20%) and aggressiveness (15%). Hallucinations were
      present in 16% of the patients (6% tactile; 4% olfactory). Nearly 9% had a family
      history of schizophrenia (higher among those with the jealous subtype) and 42%
      had a comorbid axis II diagnosis (mostly paranoid personality disorder).
      Depression was significantly more frequent among the persecutory and jealous
      types. Finally, global functioning was significantly better among jealous and
      mixed types and worse amongst erotomanic and grandiose cases (p=0.008).
      CONCLUSIONS: In the absence of other similar empirical data, this modest study
      provides unique empirical evidence of some clinical and risk correlates of DD and
      its subtypes.

PMID- 18082380
TI  - Temporal association of onset of daily smoking with adolescent substance use and
      psychiatric morbidity.
AB  - OBJECTIVE: The association between cigarette smoking and psychiatric disorders is
      well established for adult populations. However, only limited number of studies
      has investigated whether the young onset age of daily smoking (DS) among
      adolescents is associated with psychiatric morbidity and vice versa. METHODS:
      Data from 508 adolescents admitted to psychiatric hospitalization were collected.
      Cox proportional hazard model were used to compare the initiation of DS between
      adolescents with and without substance use (SUD), and other psychiatric
      disorders. RESULTS: Rates of DS were high in each diagnostic category. Boys
      started smoking at younger age (mean 12.4 years) than girls (13.0 years). Both
      boys and girls diagnosed with conduct or oppositional defiant disorders (COD) and
      also girls with SUD started daily smoking earlier as compared to those of same
      gender without these disorders.COD were found to be primary to the initiation of
      DS among boys. SUD, psychotic, and depressive disorders (DEP) were found to be
      secondary to DS among both genders. CONCLUSIONS: DS in adolescence is related
      with later SUD. COD are associated with subsequent initiation of DS among boys.
      The temporal gap between smoking initiation and COD is shorter among girls.
      Gender difference plays a role in association of DS and DEP. Initiation of DS at
      very early age should alert health care professionals of development of later
      psychopathology, especially SUD.

PMID- 18082382
TI  - Evaluation of antitubercular drug insertion into preformed
      dipalmitoylphosphatidylcholine monolayers.
AB  - Insertion profiles of antitubercular drugs isoniazid (INH), rifampicin (RFM) and
      ethambutol (ETH) into dipalmitoylphosphatidylcholine (DPPC) membrane models were
      evaluated by Langmuir monolayer technique. Maximum drug insertion into DPPC
      monolayer was observed with rifampicin with a surface pressure increase
      (Deltapi(max)) in the range of 21-33 mN/m depending upon rifampicin
      concentration. Isoniazid had minimal insertion resulting in a lower Deltapi(max)
      of about 2-3 mN/m, suggestive of minimal interactions between INH and DPPC.
      Ethambutol surface pressure increment on insertion resulted in an intermediate
      rise in the Deltapi(max) (6-10 mN/m). Antitubercular drug combination in the
      ratio of 2 mM:0.7 mM:4.5 mM for INH:RFM:ETH, attained Deltapi(max) between 25 and
      33 mN/m. Insertion profiles similar to rifampicin were exhibited by the
      antitubercular drug mixture suggestive of predominant rifampicin insertion into
      the DPPC monolayer. The extent of drug insertion into the DPPC monolayer is
      suggestive of the drug penetration potential into biological membranes in vivo.
      Higher RFM Deltapi(max) is suggestive of excellent cell membrane penetration,
      which explains broad reach of the drug to all the organs including the
      cerebrospinal fluid while lower Deltapi(max) of INH suggests poor membrane
      penetration restricting the entry of the drug in different biological membranes.
      DPPC membrane destabilization was observed at higher antitubercular drug
      concentrations indicated by the negative slopes of the surface pressure-time
      curves. This may correlate with the dose related toxic effects observed in
      tuberculosis affected patients. Drug insertion studies offer a potential tool in
      understanding the pharmacotoxicological behavior of the various pharmacological
      agents.

PMID- 18082383
TI  - In vitro screening assays to identify natural or synthetic acetylcholinesterase
      inhibitors: thin layer chromatography versus microplate methods.
AB  - Acetylcholinesterase inhibitors (AChEI) are currently still the best available
      pharmacotherapy for Alzheimer patients. Successful screening for new AChEI relies
      on effective and fast assays. Two colorimetric screening assays frequently used
      to search for new AChEI, namely a thin layer chromatography (TLC) assay with Fast
      Blue B salt as reagent and a 96-well plate assay based on Ellman's method, were
      compared. For the majority (83%) of the 138 test compounds of natural and
      synthetic origin, the results obtained with the two assays converged and both
      screening assays were considered suitable for the generation of new hits. Fifteen
      percent of investigated compounds were classified as active with the microplate
      assay but were shown to be inactive by TLC and about 2% were measured active by
      TLC but showed to be inactive with the microplate assay. These divergences were
      not due to the main differences between the experimental protocols of the two
      screening assays, namely the different colorimetric methods and pre-incubation of
      test compounds with acetylcholinesterase (AChE). They might be explained by the
      interaction of either AChE or test compounds with the silica of the TLC plates,
      resulting in an altered affinity of the enzyme for the compounds.

PMID- 18082381
TI  - Tracheal occlusion increases the rate of epithelial branching of embryonic mouse
      lung via the FGF10-FGFR2b-Sprouty2 pathway.
AB  - Tracheal occlusion during lung development accelerates growth in response to
      increased intraluminal pressure. In order to investigate the role of internal
      pressure on murine early lung development, we cauterized the tip of the trachea,
      to occlude it, and thus to increase internal pressure. This method allowed us to
      evaluate the effect of tracheal occlusion on the first few branch generations and
      on gene expression. We observed that the elevation of internal pressure induced
      more than a doubling in branching, associated with increased proliferation, while
      branch elongation speed increased 3-fold. Analysis by RT-PCR showed that Fgf10,
      Vegf, Sprouty2 and Shh mRNA expressions were affected by the change of
      intraluminal pressure after 48h of culture, suggesting mechanotransduction via
      internal pressure of these key developmental genes. Tracheal occlusion did not
      increase the number of branches of Fgfr2b-/- mice lungs nor of wild type lungs
      cultured with Fgfr2b antisense RNA. Tracheal occlusion of Fgf10(LacZ/-)
      hypomorphic lungs led to the formation of fewer branches than in wild type. We
      conclude that internal pressure regulates the FGF10-FGFR2b-Sprouty2 pathway and
      thus the speed of the branching process. Therefore pressure levels, fixed both by
      epithelial secretion and boundary conditions, can control or modulate the
      branching process via FGF10-FGFR2b-Sprouty2.

PMID- 18082384
TI  - [Constipation in children].
AB  - Constipation is a common pediatric problem. We propose guidelines based on an
      integration of expert opinion and a review of the medical literature.
      Physiopathology, symptoms, diagnosis for functional or organic constipation,
      clinical forms and treatment are considered.

PMID- 18082385
TI  - Developing an environmentally benign process for the production of
      microparticles: amphiphilic crystallization.
AB  - The production of microparticles for inhalation typically employs jet-milling
      which can be destructive to the solid-state properties of the particles. The
      objective of the current work was to develop a crystallization process for the
      production of respirable microparticles of salmeterol xinafoate (SX) with a
      controlled particle size distribution (PSD). Solvation of SX in aqueous
      poly(ethylene glycol) 400 (PEG 400) was investigated using HPLC and FTIR. SX was
      crystallized from PEG 400 solutions by the addition of water under a variety of
      conditions of supersaturation, addition rate of antisolvent and stirring speed.
      The crystals were filtered, dried at 50 degrees C and their PSDs were determined
      by laser diffraction. A logarithmic increase in solubility of SX was observed
      with increasing concentration of PEG 400 in water enabling the aqueous
      antisolvent crystallization of SX from PEG. Similar to antisolvent
      crystallization from conventional solvents, a 2(4) factorial study showed the
      particle size to decrease with increasing supersaturation. The PSD also depended
      on the balance of meso- and micromixing determined by the crystallization
      conditions. In particular a high addition rate (200 g min(-1)) and low stirrer
      speed (400 rpm) minimized the median diameter (2.54+/-0.40 microm) and produced a
      narrow PSD (90%<8.67+/-0.77 microm) of SX particles. Amphiphilic crystallization
      provided a novel, environmentally benign method to produce microparticles of SX
      with a controlled size range.

PMID- 18082386
TI  - Functional morphology of bite mechanics in the great barracuda (Sphyraena
      barracuda).
AB  - The great barracuda, Sphyraena barracuda, is a voracious marine predator that
      captures fish with a swift ram feeding strike. While aspects of its ram feeding
      kinematics have been examined, an unexamined aspect of their feeding strategy is
      the bite mechanism used to process prey. Barracuda can attack fish larger than
      the gape of their jaws, and in order to swallow large prey, can sever their prey
      into pieces with powerful jaws replete with sharp cutting teeth. Our study
      examines the functional morphology and biomechanics of 'ram-biting' behavior in
      great barracuda where the posterior portions of the oral jaws are used to slice
      through prey. Using fresh fish and preserved museum specimens, we examined the
      jaw mechanism of an ontogenetic series of barracuda ranging from 20 g to 8.2 kg.
      Jaw functional morphology was described from dissections of fresh specimens and
      bite mechanics were determined from jaw morphometrics using the software
      MandibLever (v3.2). High-speed video of barracuda biting (1500 framess(-1))
      revealed that prey are impacted at the corner of the mouth during capture in an
      orthogonal position where rapid repeated bites and short lateral headshakes
      result in cutting the prey in two. Predicted dynamic force output of the lower
      jaw nearly doubles from the tip to the corner of the mouth reaching as high as 58
      N in large individuals. A robust palatine bone embedded with large dagger-like
      teeth opposes the mandible at the rear of the jaws providing for a scissor-like
      bite capable of shearing through the flesh and bone of its prey.

PMID- 18082387
TI  - Editorial 2008.

PMID- 18082388
TI  - Do the peptide-binding properties of diabetogenic class II molecules explain
      autoreactivity?
AB  - One seminal aspect in autoimmune diabetes is antigen presentation of beta cell
      antigens by the diabetes-propensity class II histocompatibility molecules. The
      binding properties of I-Ag7 molecules are reviewed here and an emphasis is placed
      on their selection of peptides with a highly specific sequence motif, in which
      one or more acidic amino acids are found at the carboxy end interacting at the P9
      anchoring site of I-Ag7. The reasons for the central role of I-Ag7 in the
      autoimmune response are analyzed. The insulin B chain segment 9-23 is a hot spot
      for T cell selection and a striking example of a weak MHC binding peptide that
      triggers autoreactivity.

PMID- 18082390
TI  - Geotechnical and leaching properties of flowable fill incorporating waste foundry
      sand.
AB  - Waste foundry sand (WFS) can be converted into flowable fill for geotechnical
      applications. In this study, WFS samples were obtained from 17 independent metal
      casting facilities with different casting processes, thus representing a good
      range of WFS properties. The laboratory studies include physical, geotechnical
      and leaching properties of flowable fills consisting of WFS, cement, and fly ash
      mixed to different water contents. The main properties measured include WFS
      physical properties (density, particle gradation, grain shape, and fine content),
      WFS flowable fill geotechnical properties (unconfined compressive strength,
      hydraulic conductivity, setting time, and bleeding), and the fill's leaching
      properties (heavy metals and organics in the bleed water and the leachate
      extracted from hardened WFS flowable fills). The test results indicate that in
      terms of the physical properties, most of the data fall within narrow ranges,
      although data from the copper/aluminum-based WFS samples might fall beyond the
      ranges. Geotechnical properties of WFS flowable fills in both fresh and hardened
      phases were verified conforming to the features of specified flowable fills.
      Material leaching analyses indicate that the toxicity of WFS flowable fills is
      below regulated criteria. A mix formulation range originated from this study is
      proposed for the design of WFS made flowable fill.

PMID- 18082391
TI  - Fundamental characteristics of input waste of small MSW incinerators in Korea.
AB  - Waste incineration in a small incinerator is a simple and convenient way of
      treating waste discharged from small areas or from large facilities and buildings
      such as business centers, marketplaces, factories, and military units. Despite
      their ostensible advantages, however, many small incinerators frequently suffer
      from serious problems, e.g., unsystematic waste feeding, unstable combustion,
      deficient air pollution control devices, and consequently, environmental
      pollution. To obtain a better understanding of the characterization of wastes in
      small incinerators, we investigated a series of fundamental characteristics,
      i.e., physical composition, bulk density, proximate and ultimate analysis,
      potential energy content, and so on. The main waste components in small
      incinerators were identified as paper and plastic; the proportion of food waste
      was less than that in large incinerators. Especially, a low ratio of food waste
      had a strong influence on other waste characteristics, e.g., lower moisture
      content and bulk density, and higher potential energy. On the other hand, in
      contrast with that of HCl, there was no distinguishable linear relationship
      between Cl content in waste and PCDD/DF concentration in combustion gas.

PMID- 18082389
TI  - Division of labor, plasticity, and crosstalk between dendritic cell subsets.
AB  - For years, dendritic cell (DC) biologists have oscillated between two seemingly
      antagonistic ideas: functional specialization (division of labor) of DC subsets
      and plasticity (multitasking). More recently, a third hypothesis is gathering
      support: crosstalk between functionally distinct DC subsets. This reveals a
      previously unappreciated hierarchy of organization within the DC system, and
      provides a conceptual framework to understand how cooperation between
      functionally distinct, yet plastic, DC subsets can shape adaptive immunity and
      immunological memory. Here we review the recent advances in this area.

PMID- 18082392
TI  - Measuring permeability with a whole cell-based biosensor as an alternate assay
      for angiogenesis: comparison with common in vitro assays.
AB  - Angiogenesis plays cardinal role in normal developmental processes as well as in
      numerous pathologies. Multiple cytokines are released and act simultaneously to
      activate endothelial cells in vivo. The present study investigated the relative
      ability of vascular endothelial growth factor (VEGF), basic fibroblast growth
      factor (bFGF), hepatocyte growth factor (HGF), tumor necrosis factor-alpha (TNF
      alpha) in modulating cell monolayer permeability, migration, proliferation and
      tube formation individually and in combination. While the common methods for
      assaying angiogenesis were conducted for studying cell migration, proliferation
      and differentiation, endothelial cell monolayer permeability studies were carried
      out using a whole cell-based biosensor. The biosensor, consisting of a confluent
      monolayer of human umbilical vein endothelial cells (HUVECs) on a potassium ion
      selective electrode, takes advantage of cell monolayer permeability dysfunction
      to detect the presence of small quantities of cytokines. When a confluent
      monolayer of cells was formed on the membrane surface, the response of the
      electrode toward the marker ion, potassium, was inhibited. The response obtained
      after exposing this sensor to different cytokines for 1 and 3h, can be attributed
      to the modulation of monolayer permeability by these cytokines. The present study
      demonstrated that at the concentrations experimented with, the relative change in
      permeability assay in the presence of cytokines compared to the control was much
      higher than that observed in other assays, thereby bolstering the potential of
      the biosensor to act as a quick screening tool for angiogenesis.

PMID- 18082393
TI  - In pursuit of a super producer-alternative paths to high producing recombinant
      mammalian cells.
AB  - Recombinant mammalian cells are used to produce numerous, high-value protein
      therapeutics. Generating hyper-producing cell lines is crucial for delivery of
      products to ailing patients. Better understanding of the complex trait of
      hyperproductivity can facilitate the creation of hyper-producing cell lines.
      Ruminating over the reported transcriptomic and proteomic studies, we attempt to
      assess whether high productivity response is a result of minute changes occurring
      globally or large alterations observed locally at the molecular level. We present
      here our philosophical perspective on the alternative routes to high
      productivity. We contend that given the advances in genome-scale technologies and
      data analysis approaches, insights gained from elucidating the gene-trait
      relationship underlying hyperproductivity will accelerate the development of
      hyperproductive processes.

PMID- 18082395
TI  - Case-control study on childhood cancer in the vicinity of nuclear power plants in
      Germany 1980-2003.
AB  - The 1984 Windscale study raised concern about a possible association between
      living in the vicinity of nuclear power plants and childhood cancer. No such
      effect for all cancers was seen in ecological studies in Germany (1980-1995).
      Results from exploratory analyses led to a new study. Pre-selected areas around
      all 16 major nuclear power plants in Germany formed the study area. The design is
      a matched case-control study; cases are all cancers under five years diagnosed in
      1980-2003: 1592 cases, and 4735 controls. Inverse distance of place of residence
      to the nearest nuclear power plant at the time of diagnosis was used as the
      independent variable in a conditional logistic regression model. Results show an
      increased risk for childhood cancer under five years when living near nuclear
      power plants in Germany. The inner 5-km zone shows an increased risk (odds ratio
      1.47; lower one-sided 95% confidence limit 1.16). The effect was largely
      restricted to leukaemia. The results are compatible with the corresponding
      subgroups in the previous German ecological studies, with which this study shares
      most of the cases. They contrast with the lack of an effect observed or expected
      from other studies due to low doses from routine nuclear power plant operation.

PMID- 18082394
TI  - Circuit reconstruction tools today.
AB  - To understand how a brain processes information, we must understand the structure
      of its neural circuits-especially circuit interconnection topologies and the cell
      and synapse molecular architectures that determine circuit-signaling dynamics.
      Our information on these key aspects of neural circuit structure has remained
      incomplete and fragmentary, however, because of limitations of the best available
      imaging methods. Now, new transgenic tool mice and new image acquisition tools
      appear poised to permit very significant advances in our abilities to reconstruct
      circuit connection topologies and molecular architectures.

PMID- 18082396
TI  - Biological phosphorus removal in sequencing batch reactor with single-stage oxic
      process.
AB  - The performance of biological phosphorus removal (BPR) in a sequencing batch
      reactor (SBR) with single-stage oxic process was investigated using simulated
      municipal wastewater. The experimental results showed that BPR could be achieved
      in a SBR without anaerobic phase, which was conventionally considered as a key
      phase for BPR. Phosphorus (P) concentration 0.22-1.79 mg L(-1) in effluent can be
      obtained after 4h aeration when P concentration in influent was about 15-20 mg L(
      1), the dissolved oxygen (DO) was controlled at 3+/-0.2 mg L(-1) during aerobic
      phase and pH was maintained 7+/-0.1, which indicated the efficiencies of P
      removal were achieved 90% above. Experimental results also showed that P was
      mainly stored in the form of intracellular storage of polyphosphate (poly-P), and
      about 207.235 mg phosphates have been removed by the discharge of rich-phosphorus
      sludge for each SBR cycle. However, the energy storage poly-beta
      hydroxyalkanoates (PHA) was almost kept constant at a low level (5-6 mg L(-1))
      during the process. Those results showed that phosphate could be transformed to
      poly-P with single-stage oxic process without PHA accumulation, and BPR could be
      realized in net phosphate removal.

PMID- 18082397
TI  - Shell cracking strength in almond (Prunus dulcis [Mill.] D.A. Webb.) and its
      implication in uses as a value-added product.
AB  - Researchers are currently developing new value-added uses for almond shells, an
      abundant agricultural by-product. Almond varieties are distinguished by
      processors as being either hard or soft shelled, but these two broad classes of
      almond also exhibit varietal diversity in shell morphology and physical
      characters. By defining more precisely the physical and chemical characteristics
      of almond shells from different varieties, researchers will better understand
      which specific shell types are best suited for specific industrial processes.
      Eight diverse almond accessions were evaluated in two consecutive harvest seasons
      for nut and kernel weight, kernel percentage and shell cracking strength. Shell
      bulk density was evaluated in a separate year. Harvest year by almond accession
      interactions were highly significant (p0.01) for each of the analyzed variables.
      Significant (p0.01) correlations were noted for average nut weight with kernel
      weight, kernel percentage and shell cracking strength. A significant (p0.01)
      negative correlation for shell cracking strength with kernel percentage was
      noted. In some cases shell cracking strength was independent of the kernel
      percentage which suggests that either variety compositional differences or shell
      morphology affect the shell cracking strength. The varietal characterization of
      almond shell materials will assist in determining the best value-added uses for
      this abundant agricultural by-product.

PMID- 18082398
TI  - Pyrolysis of safflower (Charthamus tinctorius L.) seed press cake in a fixed-bed
      reactor: part 2. Structural characterization of pyrolysis bio-oils.
AB  - Biomass in the form of agricultural residues is becoming popular among new
      renewable energy sources, especially given its wide potential and abundant usage.
      Pyrolysis is the most important process among the thermal conversion processes of
      biomass. In this study, the various characteristics of bio-oils acquired under
      different pyrolysis conditions from safflower seed press cake (SPC) were
      identified. The elemental analyses and calorific values of the bio-oils were
      determined, and then the chemical compositions of the bio-oils were investigated
      using chromatographic and spectroscopic techniques such as column chromatography,
      (1)H NMR, FTIR and GC. The fuel properties of the bio-oil such as kinematic
      viscosity, flash point, density, water content and ASTM distillation were also
      determined. Chemical compositions of bio-oils showed that some quantities of
      hydrocarbons were present, while oxygenated and polar fractions dominated. The
      bio-oils obtained from safflower seed press cake were presented as an
      environmentally friendly feedstock candidate for biofuels and chemicals.

PMID- 18082399
TI  - Cadmium biosorption on Spirulina platensis biomass.
AB  - Dry biomass of Spirulina platensis re-hydrated for 48 h was employed as a
      biosorbent in tests of cadmium(II) removal from water. Various concentrations of
      biomass (from 1 to 4 g l(-1)) and metal (from 100 to 800 mg l(-1)) were tested.
      Low biomass levels (X(o)2 g l(-1)) ensured metal removal up to 98% only at Cd(0)=
      100 and 200 mg l(-1), while X(o)2.0 g l(-1) were needed at Cd(0)=400 mg l(-1) to
      achieve satisfactory results. Whereas X(o)=4.0 g l(-1) was effective to remove up
      to Cd(0)=500 mg l(-1), a further increase in metal concentration (Cd(0)=600 and
      800 mg l(-1)) led to progressive worsening of the system performance. At a given
      biomass levels, the kinetics of the process was better at low Cd(2+)
      concentrations, while, raising the adsorbent level from 1.0 to 2.0 g l(-1) and
      then to 4.0 g l(-1), the rate constant of biosorption increased by about one
      order of magnitude in both cases and the adsorption capacity of the system
      progressively decreased from 357 to 149 mg g(-1).

PMID- 18082400
TI  - Comparison of aerobic and anaerobic degradation of municipal solid waste in
      bioreactor landfills.
AB  - Two landfill bioreactors were operated under aerobic and anaerobic conditions in
      a thermo-insulated room at a constant temperature of 32 degrees C. Reactors were
      filled with 19.5 kg of shredded synthetic solid waste prepared according to the
      average municipal solid waste compositions determined in Istanbul and operated
      under wet-tomb management strategy by using leachate recirculation. Aerobic
      conditions in the reactor were developed by using an air compressor. The results
      of experiments indicated that aerobic reactor had higher organic, nitrogen,
      phosphorus and alkali metal removal efficiencies than the anaerobic one.
      Furthermore, stabilization time considerably decreased when using aerobic
      processes with leachate recirculation compared to the anaerobic system with the
      same recirculation scheme.

PMID- 18082401
TI  - Syntheses of tetrahydrothiophenes and tetrahydrofurans and studies of their
      derivatives as melanocortin-4 receptor ligands.
AB  - Piperazinebenzylamine derivatives from trans-4-(4
      chlorophenyl)tetrahydrothiophene-3-carboxylic acid 6 and its S-oxide 7 and
      sulfone 8, and the tetrahydrofuran 9 and its two regioisomers 11 and 13 were
      synthesized and studied for their binding affinities at the human melanocortin-4
      receptor. These five-membered ring constrained compounds possessed similar or
      lower potency compared to the acyclic analogs.

PMID- 18082402
TI  - Synthesis and anti-HIV activity of 2'-fluorine modified nucleoside phosphonates:
      analogs of GS-9148.
AB  - Modified purine analogs of GS-9148 [5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro
      furan-2-yloxymethyl]-phosphonic acid (2'-Fd4AP) were synthesized and their anti
      HIV potency evaluated. The antiviral activity of guanosine analog (2'-Fd4GP) was
      comparable that of to 2'-Fd4AP in MT-2 cells, but selectivity was reduced.

PMID- 18082403
TI  - Prognosis of patients with local recurrence after mastectomy or conservative
      surgery for early-stage invasive breast cancer.
AB  - Between 1983 and 1987, 1309 women with stage I or II breast cancer underwent
      mastectomy (n=894) or conservative surgery (CS, n=415). Of these patients, 124
      developed an isolated local recurrence (ILR): chest wall, 56 and in-breast, 68.
      The 10-year actuarial rate of cause-specific survival after treatment for ILR was
      52%. On multivariate analysis three independent prognostic factors for the risk
      of death after ILR were identified: operability of recurrence (operable vs.
      inoperable, relative risk [RR]: 5.9), age at initial diagnosis (>40 vs. < or = 40
      years, RR: 2.2) and time to ILR (>24 vs. < or = 24 months, RR: 2). Initial lymph
      node stage (negative vs. positive) showed borderline significance (p=0.06), and
      type of initial surgery (CS vs. mastectomy) and recurrent tumor grade (1-2 vs. 3)
      were not independent predictors of survival. In the mastectomy group, single
      surgical scar recurrence with initial node negative stage predicted good
      prognosis, and the 10-year survival was 85%. In the CS group, the 10-year
      survival rate was 88% with new primary tumor and 54% with true recurrence
      (p=0.01), and the type of salvage surgery (mastectomy vs. repeat complete
      excision) had no significant impact on survival (p=0.2). The majority (n=44) of
      CS patients developed < or = 2 cm in-breast recurrence, and the 10-year survival
      was 81% after both salvage excision (n=28) and mastectomy (n=16). The identified
      unfavorable prognostic factors are pointers of the forthcoming systemic
      progression. Patients with < or = 2 cm in-breast recurrence might receive a
      second CS.

PMID- 18082404
TI  - SAS-6 is a cartwheel protein that establishes the 9-fold symmetry of the
      centriole.
AB  - Centrioles consist of nine-triplet microtubules arranged in rotational symmetry.
      This structure is highly conserved among various eukaryotic organisms and serves
      as the base for the ciliary axoneme. Recently, several proteins such as SAS-6
      have been identified as essential to the early process of centriole assembly, but
      the mechanism that produces the 9-fold symmetry is poorly understood. In C.
      elegans and Drosophila, SAS-6 has been suggested to function in the formation of
      a centriolar precursor, a central tube that then assembles nine-singlet
      microtubules on its surface. However, the generality of the central tube is not
      clear because in many other organisms, the first structure appearing in the
      centriole assembly is not a tube but a flat amorphous ring or a cartwheel-a
      structure with a hub and nine radiating spokes. Here we show that in
      Chlamydomonas the SAS-6 protein localizes to the central part of the cartwheel
      and that a null mutant of SAS-6, bld12, lacks that part. Intriguingly, this
      mutant frequently has centrioles composed of 7, 8, 10, or 11 triplets in addition
      to 9-triplet centrioles. We presume that, in many organisms, SAS-6 is an
      essential component of the cartwheel, a structure that stabilizes the 9-triplet
      structure.

PMID- 18082405
TI  - Short-wavelength light sensitivity of circadian, pupillary, and visual awareness
      in humans lacking an outer retina.
AB  - As the ear has dual functions for audition and balance, the eye has a dual role
      in detecting light for a wide range of behavioral and physiological functions
      separate from sight. These responses are driven primarily by stimulation of
      photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short
      wavelength ( approximately 480 nm) blue light and remain functional in the
      absence of rods and cones. We examined the spectral sensitivity of non-image
      forming responses in two profoundly blind subjects lacking functional rods and
      cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found
      that short-wavelength light preferentially suppressed melatonin, reset the
      circadian pacemaker, and directly enhanced alertness compared to 555 nm exposure,
      which is the peak sensitivity of the photopic visual system. In an action
      spectrum for pupillary constriction, the female subject exhibited a peak spectral
      sensitivity (lambda(max)) of 480 nm, matching that of the pRGCs but not that of
      the rods and cones. This subject was also able to correctly report a threshold
      short-wavelength stimulus ( approximately 480 nm) but not other wavelengths.
      Collectively these data show that pRGCs contribute to both circadian physiology
      and rudimentary visual awareness in humans and challenge the assumption that rod-
      and cone-based photoreception mediate all "visual" responses to light.

PMID- 18082406
TI  - The influence of cell mechanics, cell-cell interactions, and proliferation on
      epithelial packing.
AB  - BACKGROUND: Epithelial junctional networks assume packing geometries
      characterized by different cell shapes, neighbor number distributions and areas.
      The development of specific packing geometries is tightly controlled; in the
      Drosophila wing epithelium, cells convert from an irregular to a hexagonal array
      shortly before hair formation. Packing geometry is determined by developmental
      mechanisms that likely control the biophysical properties of cells and their
      interactions. RESULTS: To understand how physical cellular properties and
      proliferation determine cell-packing geometries, we use a vertex model for the
      epithelial junctional network in which cell packing geometries correspond to
      stable and stationary network configurations. The model takes into account cell
      elasticity and junctional forces arising from cortical contractility and
      adhesion. By numerically simulating proliferation, we generate different network
      morphologies that depend on physical parameters. These networks differ in polygon
      class distribution, cell area variation, and the rate of T1 and T2 transitions
      during growth. Comparing theoretical results to observed cell morphologies
      reveals regions of parameter space where calculated network morphologies match
      observed ones. We independently estimate parameter values by quantifying network
      deformations caused by laser ablating individual cell boundaries. CONCLUSIONS:
      The vertex model accounts qualitatively and quantitatively for the observed
      packing geometry in the wing disc and its response to perturbation by laser
      ablation. Epithelial packing geometry is a consequence of both physical cellular
      properties and the disordering influence of proliferation. The occurrence of T2
      transitions during network growth suggests that elimination of cells from the
      proliferating disc epithelium may be the result of junctional force balances.

PMID- 18082407
TI  - Factors affecting anteroposterior instability following cruciate-retaining total
      knee arthroplasty in patients with rheumatoid arthritis.
AB  - Controversy persists concerning around posterior cruciate ligament (PCL)
      retention in total knee arthroplasty (TKA) for patients with rheumatoid arthritis
      (RA). This study investigated factors affecting anteroposterior (AP) instability
      following cruciate-retaining (CR)-TKA. In a consecutive series of 70 knees from
      52 RA patients, total displacement (TD) was measured using a KT-2000 arthrometer
      before and after CR-TKA under anesthesia, and changes in TD were defined as
      DeltaTD. TD was also measured under anesthesia in 65 knees from 48 RA patients at
      a mean of 7.5 years after CR-TKA. Mean postoperative TD was 9.4+/-0.95 mm,
      representing an increase of about 1.5-1.8 mm compared to preoperative TD, and
      possibly reflecting resection of the anterior cruciate ligament. Correlation
      analysis revealed significant negative correlations between DeltaTD and both
      preoperative flexion angle (r=-0.67, p<0.001) and preoperative extension angle
      (r=-0.63, p<0.001), suggesting that TD in knees with flexion contracture
      increased postoperatively. At medium-term follow-up, no patients displayed AP
      instability, and mean TD was 8.3+/-0.48 mm. A significant correlation was found
      between TD and permissible flexion angle (r=0.61, p<0.001). These results
      indicate that TD is basically maintained during the course of CR-TKA in RA, but
      may be slightly affected by factors other than the PCL itself.

PMID- 18082409
TI  - Structural requirements for the stability of novel cephalosporins to AmpC beta
      lactamase based on 3D-structure.
AB  - AmpC beta-lactamase is one of the leading causes of Pseudomonas aeruginosa (P.
      aeruginosa) resistance to cephalosporins. FR259647 is a cephalosporin having a
      novel pyrazolium substituent at the 3-position and exhibits excellent activity
      (MIC=1 microg/mL) against the AmpC beta-lactamase overproducing P. aeruginosa
      FP1380 strain in comparison with the third-generation cephalosporins FK518
      [Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and
      Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 454; Abstracts of Papers,
      30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta,
      GA, October 21-24, 1990, Abs. 455; Abstracts of Papers, 30th Interscience
      Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24,
      1990, Abs. 456; Abstracts of Papers, 30th Interscience Conference on
      Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs.
      457] (MIC=16 microg/mL) and ceftazidime (CAZ) (MIC=128 microg/mL). The stability
      of FR259647 and FK518 to AmpC beta-lactamase was evaluated using MIC assays
      against both the P. aeruginosa PAO1 strain and a PAO1 mutant strain overproducing
      AmpC beta-lactamase as a differential assay, which indicates that the main
      difference derives from their stability to AmpC beta-lactamase. A structural
      analysis using computer simulations indicated that the difference in stability
      may be due to steric hindrance of the 3-position substituents causing
      differential affinity. This steric hindrance may disturb entry of the
      cephalosporins into the binding pocket. We predicted the possibility of
      inhibition of entry as a potential means of enhancing stability by conformational
      analysis. In order to validate this speculation, novel FR259647 derivatives 4-9
      were designed, calculated, synthesized, and evaluated. As a result, we
      demonstrated that their probability of entry correlated with the MIC ratio of the
      mutant strain to the parent strain and supports the validity of our model.

PMID- 18082408
TI  - alpha- and beta-substituted phosphonate analogs of LPA as autotaxin inhibitors.
AB  - Autotaxin (ATX) is an attractive pharmacological target due to its
      lysophospholipase D activity which leads to the production of lysophosphatidic
      acid (LPA). Blockage of ATX produced LPA by small molecules could be a potential
      anticancer chemotherapy. In our previous study, we have identified the two beta
      hydroxy phosphonate analogs of LPA (compounds f17 and f18) as ATX inhibitors.
      With this work, we investigated alpha- and beta-substituted phosphonate analogs
      of LPA and evaluated them for ATX inhibitory activity. The stereochemistry of
      beta-hydroxy phosphonates was also studied.

PMID- 18082410
TI  - Fluorinated methylenecyclopropane analogues of nucleosides. Synthesis and
      antiviral activity of (Z)- and (E)-9-{[(2-fluoromethyl-2-hydroxymethyl)
      cyclopropylidene]methyl}adenine and -guanine.
AB  - Synthesis and antiviral activity of the title fluoromethylenecyclopropane
      analogues 15a, 15b, 16a, and 16b is described. Methylenecyclopropane carboxylate
      was first transformed to 2,2-bis-hydroxymethylmethylenecyclopropane. Selective
      monoacetylation followed by introduction of fluorine gave 2-acetoxymethyl-2
      fluoromethylmethylenecyclopropane as the key intermediate. The synthesis of
      analogues 15a, 15b, 16a, and 16b then followed alkylation-elimination procedure
      as described previously for other methylenecyclopropane analogues [corrected]
      Compounds 15a, 15b, 16a and 16b were not active against Epstein-Barr virus (EBV)
      [corrected] Analogue 15a inhibited hepatitis C virus by virtue of its
      cytotoxicity and it moderately inhibited replication of the Towne strain of human
      cytomegalovirus (HCMV). The E-isomer 16a was a substrate for adenosine deaminase,
      whereas the Z-isomer 15a was not deaminated.

PMID- 18082411
TI  - High-resolution Z-contrast imaging and EELS study of functional oxide materials.
AB  - Functional complex-oxide materials show a wide variety of properties and
      behaviors that cannot be found in any other class of materials, including high
      temperature superconductivity and colossal magneto resistance. Consequently, this
      group of oxide materials has become the focus of many experimental as well as
      theoretical studies, aiming at understanding the fundamental mechanisms and
      properties that govern these complex structures. Here, we will review our high
      resolution Z-contrast imaging and electron energy-loss studies of two complex
      oxide materials systems, more specifically low-angle tilt grain-boundaries in
      YBa(2)Cu(3)O(7) (YBCO), and the spin-state transition in LaCoO(3). It will be
      shown that the O K-edge pre-peak can be used to quantify the hole-concentration
      in the vicinity of the dislocation core in YBCO, as well as to determine the
      Co(3+) spin-state in LaCoO(3).

PMID- 18082412
TI  - A microRNA-based gene dysregulation pathway in Huntington's disease.
AB  - Huntington's disease (HD) is a dominantly-inherited neurodegenerative disorder
      which is incurable and ultimately fatal. HD is characterised by widespread mRNA
      dysregulation, particularly in neurons of the forebrain, by mechanisms which are
      not fully understood. Such dysregulation has been demonstrated to result, in
      part, from aberrant nuclear localisation of the transcriptional repressor, REST.
      Here, we show that expression of a number of neuronal-specific microRNAs is also
      dysregulated in HD tissues, probably as a result of increased repression by REST.
      This phenomenon is observed in both murine models of HD and in the brains of
      human HD sufferers. MicroRNA loss is reflected in increased levels of a number of
      target messenger RNAs. These data are the first to demonstrate a role for
      microRNAs in HD, and indicate that the molecular aetiology of HD is reflected in
      a loss of neuronal identity, caused in part by dysregulation of both
      transcriptional and post-transcriptional mechanisms.

PMID- 18082413
TI  - The antiphospholipid syndrome and heart valve surgery.
AB  - The antiphospholipid syndrome (APLS) is a complex autoimmune disease often
      connected to systemic lupus erythematodes. Main features are thromboses, fetal
      loss and specific antibodies. The involved autoantibodies are directed against
      plasma proteins such as beta2glycoprotein1 (beta2GPI) or prothrombin which depend
      on negatively charged phospholipids. Direct antibodies against phospholipids are
      of no importance for APLS. Clotting tests such as activated partial
      thromboplastin time or diluted Russell's viper venom test (dRVVT) can show a
      prolonged time for coagulation despite a prothrombotic state in vivo but the
      investigator needs awareness about disturbing phospholipid sources and other
      influential factors. Enzyme linked immuno sorbent assay tests for antibodies
      against cardiolipin, beta2GPI and prothrombin are valuable solid phase tests with
      different specificity. Antiphospholipid, anticardiolipin or lupus anticoagulant
      are misnomers in connection with APLS. They are preserved as a reminiscence of
      the pioneering work on the way to the still not exactly revealed basics of APLS.
      Valve operations in APLS patients seem to be rare; a meta-analysis of 57 cases
      proves that the perioperative management is, at the moment, an empirical approach
      with high morbidity and mortality in these young patients.

PMID- 18082414
TI  - Improved results with single-stage total correction of Taussig-Bing anomaly.
AB  - OBJECTIVE: The arterial-switch operation (ASO) for management of Taussig-Bing
      anomaly is associated with important morbidity, mainly related to multiple
      associated cardiac anomalies. Our surgical management has evolved to suggest a
      single-stage total repair strategy tailored to address all abnormalities on an
      individual basis. We examine the efficacy of this treatment approach. METHODS:
      Thirty-three children, (infants n=29), with Taussig-Bing underwent ASO (1979
      2005). In our earlier experience (group 1, n=17), initial palliation was
      performed as needed, including pulmonary-artery banding (n=9), coarctation repair
      (n=6), and atrial septostomy (n=3) followed by ASO at a later age. In our later
      experience (group 2, n=16), single-stage total repair was performed; ASO with
      ventricular septal defect closure and baffling of left ventricle to neo-aorta
      performed in neonates with arch obstruction (n=8), or at age 6 weeks in those
      with no arch obstruction (n=8). Concomitant relief of right-ventricle outflow
      tract obstruction (RVOTO) was performed in 14 patients. Demographics and
      operative variables affecting outcomes were analyzed. RESULTS: Mean age at
      operation for group 1 and 2 patients was 312+/-477 and 42+/-31 days (p<0.0001).
      Aortic arch obstruction (52%), sub-aortic RVOTO (61%) and unusual coronary
      patterns (52%) were similar for both groups. One-year survival for group 1 and 2
      patients was 47+/-5% and 100% (p=0.001). Associated anomalies such as great
      vessels position, arch obstruction, and unusual coronaries were not significant
      risk factors for mortality on multivariable analysis. Ten-year freedom from RVOT
      and arch re-operation was 55+/-5% and 96+/-4%. Five-year event-free survival for
      groups 1 and 2 was 35+/-6% and 87+/-1% (p=0.0016). Significant factors affecting
      event-free survival were group 1 (HR 108, p=0.0005), and larger weight at surgery
      (HR 1.3, p=0.02). CONCLUSIONS: The Taussig-Bing anomaly is complex and often
      associated with other cardiac anomalies (arch obstruction, RVOTO, unusual
      coronary pattern). Advances in perioperative care have significantly mitigated
      mortality. In our experience with single-stage total repair, event-free survival,
      especially freedom from RVOT re-operation, has significantly improved.

PMID- 18082415
TI  - Algorithm for primary closure in sternal wound infection: a single institution 10
      year experience.
AB  - OBJECTIVES: To evaluate a simple treatment algorithm in sternal wound infection
      (SWI) allowing for primary closure and to describe the different surgical
      techniques and their associated morbidity and mortality. METHODS: A retrospective
      analysis of all patients operated on between 1996 and 2004 in a single tertiary
      care institution. All epidemiological and surgical data were prospectively
      collected in our database. Univariate and multivariate analysis were used to
      determine preoperative and perioperative risks factors for 90-day and long-term
      mortality. RESULTS: Out of 5905 procedures, 146 sternal wound infections were
      documented (2.4%). The respective incidence of SWI for CABG, isolated valve, or
      combined procedures were 2.8%, 1.1%, and 3.2%. Pathogens involved were S.
      epidermidis (44.5%), S. aureus (31.5%), and gram-negative rods (19.2%). Re
      operation was required in 131/146 patients. Mean time to the first re-operation
      was 17.3+/-12 days. Modalities of treatment consisted of drainage alone (44
      patients), rewiring (25 patients), debridement, rewiring and mediastinal lavage
      (52 patients), and partial/complete sternal resection (10 patients). Additional
      procedures were required in 49 patients (37.7%). The 90-day mortality for
      uninfected patients and patients with superficial SWI were 4.4% and 2.8% (p=0.78)
      whereas for patients with deep SWI, 90-day mortality was 14.5% (DSWI vs others,
      p<0.0001). CONCLUSIONS: Deep sternal wound infection (DSWI) remains a dreadful
      complication in contemporary cardiac surgery while risk factors are currently
      well defined. Using a simple approach of primary closure together with liberal
      use of vascularized flaps has allowed us to achieve satisfactory short-term
      outcome in this subset of patients.

PMID- 18082416
TI  - Shall we operate? Preoperative assessment in elderly cancer patients (PACE) can
      help. A SIOG surgical task force prospective study.
AB  - BACKGROUND: A number of elderly cancer patients do not receive standard surgery
      for solid tumors because they are considered unfit for treatment as a consequence
      of inaccurate estimation of the operative risk. To tailor treatment to onco
      geriatric series, oncologists are now beginning to use a comprehensive geriatric
      assessment (CGA). This study investigates the value of an extended CGA in
      assessing the suitability of elderly patients for surgical intervention. PATIENTS
      AND METHODS: Preoperative assessment of cancer in the elderly (PACE) incorporates
      validated instruments including the CGA, an assessment of fatigue and performance
      status and an anaesthesiologist's evaluation of operative risk. An international
      prospective study was conducted using 460 consecutively recruited elderly cancer
      patients who received PACE prior to elective surgery. Mortality, post-operative
      complications (morbidity) and length of hospital stay were recorded up to 30 days
      after surgery. RESULTS: Poor health in relation to disability (assessed using the
      instrumental activities of daily living (IADL)), fatigue and performance status
      (PS) were associated with a 50% increase in the relative risk of post-operative
      complications. Multivariate analysis identified moderate/severe fatigue, a
      dependent IADL and an abnormal PS as the most important independent predictors of
      post-surgical complications. Disability assessed by activities of daily living
      (ADL), IADL and PS were associated with an extended hospital stay. CONCLUSION:
      PACE represents a valuable tool in enhancing the decision process concerning the
      candidacy of elderly cancer patients for surgical intervention and can reduce
      inappropriate age-related inequity in access to surgical intervention. It is
      recommended that PACE be used routinely in surgical practice.

PMID- 18082417
TI  - Innate immunity, insulin resistance and type 2 diabetes.
AB  - Recent evidence has disclosed previously unrecognized links among insulin
      resistance, obesity, circulating immune markers, immunogenetic susceptibility,
      macrophage function and chronic infection. Genetic variations leading to altered
      production or function of circulating innate immune proteins, cellular pattern
      recognition receptors and inflammatory cytokines have been linked with insulin
      resistance, type 2 diabetes, obesity and atherosclerosis. Cellular innate immune
      associations with obesity and insulin resistance include increased white blood
      cell count and adipose tissue macrophage numbers. The innate immune response is
      modulated possibly by both predisposition (genetic or fetal programming), perhaps
      owing to evolutionary pressures caused by acute infections at the population
      level (pandemics), and chronic low exposure to environmental products or
      infectious agents. The common characteristics shared among innate immunity
      activation, obesity and insulin resistance are summarized.

PMID- 18082419
TI  - Differentiation of isomeric compounds by two-stage proton transfer reaction time
      of-flight mass spectrometry.
AB  - We investigated a two-stage ion source for proton transfer reaction (PTR)
      ionization to achieve more selective mass spectrometric (MS) detection of
      selected volatile organic compounds (VOCs) than that achieved with commonly used
      PTR-MS instruments, which are based on single-step PTR ionization with H3O+. The
      two-stage PTR ion source generated reagent ions other than H3O+ by an initial PTR
      between H3O+ and a selected VOC, and then a second PTR ionization occurred only
      for VOCs with proton affinities larger than the affinity of the reagent VOC.
      Acetone and acetonitrile were useful as reagent VOCs because they provided
      dominant peaks as a protonated form. Using two-stage PTR-MS, we differentiated
      isomeric VOCs (for example, ethyl acetate and 1,4-dioxane) by means of
      differences in their proton affinities; protonated acetone formed the [M + H]+
      ion from ethyl acetate but not from 1,4-dioxane. The PTR-MS-derived
      concentrations agreed quantitatively with those independently determined by
      Fourier transform infrared spectroscopy (FT-IR) at parts per million by volume
      (ppmv) levels. In addition, interfering fragment ions formed from alkyl benzenes
      at m/z 79 (C6H7+) could be distinguished from the m/z 79 ion arising from
      protonation of benzene, and therefore this method would prevent overestimation of
      benzene concentrations in air samples in which both benzene and alkyl benzenes
      are present. This two-stage PTR ionization may be useful for distinguishing
      various isomeric species, including aldehydes and ketones, if appropriate reagent
      ions are selected.

PMID- 18082418
TI  - Effects of acute caffeine administration on NOS and Bax/Bcl2 expression in the
      myocardium of rat.
AB  - Caffeine is the most frequently ingested neuroactive drug in the world and it is
      largely used to delay fatigue and improve physical activity. Caffeine can
      modulate NO synthesis in cells and may influence muscular function by modifying
      the cellular cycle life-death. There is little data concerning the relationship
      between caffeine in the heart, NOS expression and apoptosis and no data regarding
      the acute effect of high doses of caffeine in the in vivo myocardium. We
      therefore studied hemodynamic NOS and Bax/Bcl2 expression in the rat myocardium
      after a single cafffeine administration. Thirty-two male rats were divided into
      six groups: the first was iv-injected with caffeine (16 mg/kg), the second with
      caffeine + L-NAME (30 mg/kg), the third with caffeine + L-arg (0.5 g/kg), the
      fourth with caffeine + L-NAME + L-arg and finally the fifth with saline. Mean
      arterial blood pressure (MAP) was monitored for 30 min, then the animals were
      killed. The sixth group was injected with caffeine and killed after 2 h. The
      hearts were isolated and processed by immunohistochemistry. We found that
      caffeine increased MAP temporarily while caffeine + L-NAME increased it for a
      longer period. In the control myocardium, all NOS isoforms were expressed. The
      Bcl2 were strongly expressed inside the perinuclear cytoplasm whereas Bax was
      very faintly detectable in the peripheral cytoplasm. In caffeine and caffeine + L
      NAME treated animals, NOS expression disappeared. Bax and Bcl2 expression did not
      vary. The l-arg administration reversed these caffeine and L-NAME effects on NOS
      expression. Two hours after caffeine, NOS expression increased and Bax and Bcl2
      expression did not vary, although Bcl2 was mainly expressed in the peripheral
      cytoplasm. We conclude that improved caffeine-induced physical performance could
      also be related to caffeine's ability to interfere with endogenous myocardial NO
      synthesis. Furthermore, we suggest that myocardial cell plays an effective anti
      apoptotic role against acute caffeine administration.

PMID- 18082420
TI  - Expression, purification and characterization of a recombinant Lipomyces starkey
      dextranase in Pichia pastoris.
AB  - The DEX gene encoding an extracellular dextranase from Lipomyces starkeyi was
      cloned into vector pPIC9k-His6 and was expressed in Pichia pastoris GS115 strain
      under the control of AOX1 promoter. After 107 h of the 5L-scaled fermentation,
      wet cells weight of the recombinant P. pastoris Mut(+) strain reached to
      588.6g/L, and the concentration of dextranase and enzyme activity in the
      supernatant were 0.46 g/L and 83900 U/L, respectively. The activity of dextranase
      was improved 17.56-fold by cation-exchange chromatography only with a final yield
      of 71.61% and the specific activity of the purified enzyme was 181.96 U/mg. The
      purified dextranase, analyzed by SDS-PAGE and Western blotting, showed only one
      homogeneous band. Then the factors affecting the dextranase activity were
      evaluated. The optimal temperature and pH was 30 degrees C and pH 4.5,
      respectively. Metal ions Al(3+), Cu(2+), Fe(3+), and SDS could completely inhibit
      the enzyme activity, whereas Mg(2+) enhanced 145% of the enzyme activity. These
      characters are much different from what was previously reported for the L.
      starkeyi dextranase that was either expressed in S. cerevisiae or purified from
      natural L. starkeyi.

PMID- 18082421
TI  - Purification of the extracellular domain of the membrane protein GlialCAM
      expressed in HEK and CHO cells and comparison of the glycosylation.
AB  - Adhesion molecules are essential for a wide range of biological and physiological
      functions, including cell-cell interactions, cell interactions with the
      extracellular matrix, cell migration, proliferation and survival. Defects in cell
      adhesion have been associated with pathological conditions such as neoplasia, and
      neurodegenerative diseases. We have identified a new adhesion molecule of the
      immunoglobulin family, GlialCAM. The same protein was recently published under
      the name hepaCAM and was suggested to be associated with hepatocellular
      carcinoma. Here we have expressed and purified the extracellular domain of this
      molecule in two mammalian expression systems, HEK and CHO cells. A three step
      purification protocol gave an over 95% pure protein. The extracellular domain of
      GlialCAM possesses several potential N- and O-glycosylation sites. Glycosylation
      is one of the most common post-translational modifications of secreted proteins
      and of the extracellular domains of membrane bound proteins. It can influence
      both the activity and the stability of the protein. The glycosylation pattern has
      been shown to depend on the cell type where the protein is expressed. We examined
      if differences in the glycosylation of this protein could be detected when it was
      expressed in the two commonly used mammalian expression systems, HEK and CHO.
      Differences in the glycosylation were detected.

PMID- 18082422
TI  - Selenomethionine labeling of large biological macromolecular complexes: probing
      the structure of marine bacterial virus PM2.
AB  - There is a need for improved tools for labeling protein species within large
      macromolecular assemblies. Here we describe a method for the efficient
      selenomethionine labeling of the membrane-containing bacterial virus PM2 for
      structural studies. By examining potential host cells a strain was found which
      was auxotrophic for methionine, and by performing a multiparameter search of
      conditions it was possible to derive a robust protocol which simultaneously
      minimized the toxic effects of the selenomethionine, so that a reasonable virus
      yield was maintained, whilst still achieving essentially complete labeling. This
      has allowed us to fingerprint the protein constituents of the virus in a
      relatively low resolution electron density map. Such a technique can be adapted
      to other macromolecule complexes studied by X-ray crystallography.

PMID- 18082423
TI  - Single particle analysis based on Zernike phase contrast transmission electron
      microscopy.
AB  - We present the first application of Zernike phase-contrast transmission electron
      microscopy to single-particle 3D reconstruction of a protein, using GroEL
      chaperonin as the test specimen. We evaluated the performance of the technique by
      comparing 3D models derived from Zernike phase contrast imaging, with models from
      conventional underfocus phase contrast imaging. The same resolution, about 12A,
      was achieved by both imaging methods. The reconstruction based on Zernike phase
      contrast data required about 30% fewer particles. The advantages and prospects of
      each technique are discussed.

PMID- 18082424
TI  - Sensing without seeing in comparative visual search.
AB  - Rensink [Rensink, R. A. (2004). Visual sensing without seeing. Psychological
      Science, 15(1), 27-32] has presented evidence suggesting visual changes may be
      sensed without an accompanying visual experience. Here, we report two experiments
      in which we monitored observers' eye-movements whilst they searched for a
      difference between two simultaneously presented images and pressed separate
      response keys when a difference was seen or sensed. We first assessed whether
      sensing performance was random by collecting ratings of confidence in the
      validity of sensing and assessing gaze location during sensing. Sensing was not
      random: fixation position and confidence ratings were different when a difference
      was present compared to catch trials. Furthermore, the uniformity of objects in
      the images and the type of difference appear to affect seeing and sensing
      differently, suggesting that these processes are dissociated. The possibility is
      discussed of a sensing mechanism that increases vigilance toward unconsciously
      registered differences, particularly changes to scene layout.

PMID- 18082425
TI  - Neuronal correlates of "free will" are associated with regional specialization in
      the human intrinsic/default network.
AB  - Recently, we proposed a fundamental subdivision of the human cortex into two
      complementary networks-an "extrinsic" one which deals with the external
      environment, and an "intrinsic" one which largely overlaps with the "default
      mode" system, and deals with internally oriented and endogenous mental processes.
      Here we tested this hypothesis by contrasting decision making under external and
      internally-derived conditions. Subjects were presented with an external cue, and
      were required to either follow an external instruction ("determined" condition)
      or to ignore it and follow a voluntary decision process ("free-will" condition).
      Our results show that a well defined component of the intrinsic system-the right
      inferior parietal cortex-was preferentially activated during the "free-will"
      condition. Importantly, this activity was significantly higher than the base-line
      resting state. The results support a self-related role for the intrinsic system
      and provide clear evidence for both hemispheric and regional specialization in
      the human intrinsic system.

PMID- 18082426
TI  - Whole brain voxel-wise analysis of single-subject serial DTI by permutation
      testing.
AB  - Diffusion tensor MRI (DTI) has been widely used to investigate brain
      microstructural changes in pathological conditions as well as for normal
      development and aging. In particular, longitudinal changes are vital to the
      understanding of progression but these studies are typically designed for
      specific regions of interest. To analyze changes in these regions traditional
      statistical methods are often employed to elucidate group differences which are
      measured against the variability found in a control cohort. However, in some
      cases, rather than collecting multiple subjects into two groups, it is necessary
      and more informative to analyze the data for individual subjects. There is also a
      need for understanding changes in a single subject without prior information
      regarding the spatial distribution of the pathology, but no formal statistical
      framework exists for these voxel-wise analyses of DTI. In this study, we present
      PERVADE (permutation voxel-wise analysis of diffusion estimates), a whole brain
      analysis method for detecting localized FA changes between two separate points in
      time of any given subject, without any prior hypothesis about where changes might
      occur. Exploiting the nature of DTI that it is calculated from multiple diffusion
      weighted images of each region, permutation testing, a non-parametric hypothesis
      testing technique, was modified for the analysis of serial DTI data and
      implemented for voxel-wise hypothesis tests of diffusion metric changes, as well
      as for suprathreshold cluster analysis to correct for multiple comparisons. We
      describe PERVADE in detail and present results from Monte Carlo simulation
      supporting the validity of the technique as well as illustrative examples from a
      healthy subject and patients in the early stages of multiple sclerosis.

PMID- 18082427
TI  - Mirroring others' emotions relates to empathy and interpersonal competence in
      children.
AB  - The mirror neuron system (MNS) has been proposed to play an important role in
      social cognition by providing a neural mechanism by which others' actions,
      intentions, and emotions can be understood. Here functional magnetic resonance
      imaging was used to directly examine the relationship between MNS activity and
      two distinct indicators of social functioning in typically-developing children
      (aged 10.1 years+/-7 months): empathy and interpersonal competence. Reliable
      activity in pars opercularis, the frontal component of the MNS, was elicited by
      observation and imitation of emotional expressions. Importantly, activity in this
      region (as well as in the anterior insula and amygdala) was significantly and
      positively correlated with established behavioral measures indexing children's
      empathic behavior (during both imitation and observation) and interpersonal
      skills (during imitation only). These findings suggest that simulation mechanisms
      and the MNS may indeed be relevant to social functioning in everyday life during
      typical human development.

PMID- 18082429
TI  - Changes in activity of striato-thalamo-cortical network precede generalized spike
      wave discharges.
AB  - The pathophysiology of generalized spike wave discharges (GSW) is not completely
      understood. Thalamus, basal ganglia and neocortex have been implicated in the
      generation of GSW, yet the specific role of each structure remains to be
      clarified. In six children with idiopathic generalized epilepsy (IGE), we
      performed combined EEG-fMRI to identify GSW-related changes in blood oxygen level
      dependent (BOLD) signal in the striato-thalamo-cortical network. In all patients,
      within-subject analysis demonstrated BOLD signal changes that preceded the GSW.
      An increase in BOLD signal in the medial thalamus started 6 s before the onset of
      the GSW. Decreases in cortical BOLD signal were mainly found in frontoparietal
      areas and precuneus starting 6 to 3 s before the GSW. All patients showed a
      decrease in BOLD signal in the head of the caudate nucleus with a variable onset.
      The temporospatial pattern of BOLD signal changes suggests that GSW on the
      cortical surface is preceded by a sequence of neuronal events in the thalamo
      cortical-striatal network. Approximately 6 s before the GSW, the thalamus shows
      an increase in neuronal activity along with regional decreases in cortical
      activity. These changes in thalamo-cortical activity are followed by a
      deactivation of the caudate nucleus. These early changes in BOLD signal may
      reflect changes in neuronal activity that contribute to the generation of GSW and
      may contribute to the transition from a normal to a generalized hypersynchronous
      pattern of neuronal activity. Our preliminary findings warrant further studies on
      a larger number of patients to explore the influence of age, medication and type
      of epileptic syndrome.

PMID- 18082428
TI  - A method for functional network connectivity among spatially independent resting
      state components in schizophrenia.
AB  - Functional connectivity of the brain has been studied by analyzing correlation
      differences in time courses among seed voxels or regions with other voxels of the
      brain in healthy individuals as well as in patients with brain disorders. The
      spatial extent of strongly temporally coherent brain regions co-activated during
      rest has also been examined using independent component analysis (ICA). However,
      the weaker temporal relationships among ICA component time courses, which we
      operationally define as a measure of functional network connectivity (FNC), have
      not yet been studied. In this study, we propose an approach for evaluating FNC
      and apply it to functional magnetic resonance imaging (fMRI) data collected from
      persons with schizophrenia and healthy controls. We examined the connectivity and
      latency among ICA component time courses to test the hypothesis that patients
      with schizophrenia would show increased functional connectivity and increased lag
      among resting state networks compared to controls. Resting state fMRI data were
      collected and the inter-relationships among seven selected resting state networks
      (identified using group ICA) were evaluated by correlating each subject's ICA
      time courses with one another. Patients showed higher correlation than controls
      among most of the dominant resting state networks. Patients also had slightly
      more variability in functional connectivity than controls. We present a novel
      approach for quantifying functional connectivity among brain networks identified
      with spatial ICA. Significant differences between patient and control
      connectivity in different networks were revealed possibly reflecting deficiencies
      in cortical processing in patients.

PMID- 18082430
TI  - Phylogeny, species limits, and biogeography of the Brazilian lizards of the genus
      Eurolophosaurus (Squamata: Tropiduridae) as inferred from mitochondrial DNA
      sequences.
AB  - Phylogenetic relationships and divergence times for 10 populations of the three
      recognized "species" of Brazilian lizards of genus Eurolophosaurus were estimated
      from 1229bp of cyt b, COI, 12S, and 16S rRNA mitochondrial gene segments.
      Eurolophosaurus is monophyletic and the basal split within the genus separates E.
      divaricatus from a clade comprising E. amathites and E. nanuzae. Three
      populations of E. divaricatus, which occurs along the western bank of Rio Sao
      Francisco, were consistently grouped together. On the east bank of the river, E.
      amathites and E. nanuzae from state of Bahia were recovered as the sister group
      of E. nanuzae populations from state of Minas Gerais. The paraphyly of E. nanuzae
      and the high divergence levels among populations of E. divaricatus strongly
      suggest that species limits in Eurolophosaurus should be revised. Even
      considering an extreme evolutionary rate of 2.8% sequence divergence per million
      years for the four gene segments analyzed together, E. divaricatus would have
      separated from the two other species by at least 5.5my ago, and E. amathites from
      E. nanuzae populations from Bahia and Minas Gerais, respectively, by 1.5 and
      3.5my. The paleolacustrine hypothesis and changes in the course of the river
      potentially explain faunal divergence in the area, but divergences are much older
      than previously admitted.

PMID- 18082431
TI  - Proteus syndrome associated with hemimegalencephaly and Ohtahara syndrome: report
      of two cases.
AB  - The authors report two cases of Brazilian children with most of the common
      syndromic features of Proteus syndrome, such as asymmetric overgrowth of tissues,
      skin abnormalities, hypotonia and mental retardation. In both patients, a
      refractory epilepsy, compatible with Ohtahara syndrome, as well as
      hemimegalencephaly, with asymmetric distribution of facial fat, were also
      diagnosed.

PMID- 18082432
TI  - A single naive CD8+ T cell precursor can develop into diverse effector and memory
      subsets.
AB  - Upon first antigen encounter, naive CD8(+) T cells get activated, clonally
      expand, and can develop into very distinct subsets, such as short-living effector
      cells or different memory subpopulations. The origin of subset diversification is
      currently unknown, but qualitative and quantitative differences in early signals
      received by individual precursor cells have been suggested as a major
      determinant. We show that transfer of a single antigen-specific naive T cell into
      a normal recipient mouse allowed recovery of clonally expanded daughter cells
      upon immunization. With this experimental approach, we conclusively demonstrated
      that a wide range of diversity could develop out of a single precursor cell,
      including different types of effector and memory T cells. Interestingly, single
      cell-derived subset diversification resembled that of polyclonal T cell responses
      in the same individual mouse, although differentiation patterns differed between
      immunization strategies. These data implicate that subset diversification is both
      shaped and synchronized during the expansion phase.

PMID- 18082434
TI  - Ultrasonographic diagnosis of septic arthritis of the distal interphalangeal
      joint in cattle.
AB  - Diagnosis of septic arthritis in the distal interphalangeal joint (SADIJ) is
      often difficult, particularly when arthrocentesis or probing of the joint space
      are inconclusive. The aim of this prospective study was to investigate the
      usefulness of ultrasonography in reinforcing a tentative clinical diagnosis of
      SADIJ in 60 Holstein-Friesian cows with septic arthritis in one distal
      interphalangeal joint (DIJ). The diagnosis of septic arthritis was based on the
      results of clinical examination and radiographic images, as well as surgical
      findings. The DIJ of the partner claw of the same foot and the normal DIJs of 18
      healthy Holstein-Friesian cows were used as controls. Visualisation, echogenicity
      and flow phenomena of the synovial fluid were assessed ultrasonographically. The
      size of the dorsal pouch of the distal interphalangeal joint (DPDIJ) was
      determined by measuring two defined distances. The DPDIJ could be imaged in all
      cows with SADIJ, although the quality of the image varied from good (63%) or
      moderate (30%) to poor (7%). The echogenicity of the synovial fluid in joints
      with SADIJ did not differ from those of the partner claws. Flow phenomena were
      seen in only 30% of the DPDIJs with septic arthritis and in none of the DPDIJs of
      the partner claws. The DPDIJ was larger in DIJs with septic arthritis than in
      those of the partner claws and controls (P<0.05). The dorsopalmar/plantar
      distance of the DPDIJ indicated a suitable sensitivity (0.97) and specificity
      (1.0) for the diagnosis of septic arthritis when a threshold value of 6mm was
      used. Ultrasonographic examination of the DIJ appeared to be a reliable method
      for confirming a tentative clinical diagnosis of septic arthritis in cattle.

PMID- 18082433
TI  - TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of
      apoptotic cells.
AB  - The T cell immunoglobulin mucin (TIM) proteins regulate T cell activation and
      tolerance. Here we showed that TIM-4 is expressed on human and mouse macrophages
      and dendritic cells, and both TIM-4 and TIM-1 specifically bound
      phosphatidylserine (PS) on the surface of apoptotic cells but not any other
      phospholipid tested. TIM-4(+) peritoneal macrophages, TIM-1(+) kidney cells, and
      TIM-4- or TIM-1-transfected cells efficiently phagocytosed apoptotic cells, and
      phagocytosis could be blocked by TIM-4 or TIM-1 monoclonal antibodies. Mutations
      in the unique cavity of TIM-4 eliminated PS binding and phagocytosis. TIM-4 mAbs
      that blocked PS binding and phagocytosis mapped to epitopes in this binding
      cavity. These results show that TIM-4 and TIM-1 are immunologically restricted
      members of the group of receptors whose recognition of PS is critical for the
      efficient clearance of apoptotic cells and prevention of autoimmunity.

PMID- 18082435
TI  - Resolution and sensitivity aspects of ultrafast J-resolved 2D NMR spectra.
AB  - Recent ultrafast techniques enable nD NMR spectra to be obtained in a single
      scan. However, resolution enhancement in the ultrafast domain leads to important
      sensitivity losses and lineshape distortions. In order to understand better
      resolution and spatial encoding aspects of continuous phase-encoding schemes, a
      theoretical and experimental comparison of different excitation patterns is
      carried out. Molecular diffusion appears to be the main cause of signal-to-noise
      ratio decrease, and a multi-echo excitation scheme is proposed to limit its
      effects when a good resolution is needed. Results obtained on 2D J-resolved
      spectra are presented.

PMID- 18082436
TI  - Sensitivity enhancement in natural-abundance solid-state 33S MAS NMR spectroscopy
      employing adiabatic inversion pulses to the satellite transitions.
AB  - The WURST (wideband uniform rate smooth truncation) and hyperbolic secant (HS)
      pulse elements have each been employed as pairs of inversion pulses to induce
      population transfer (PT) between the four energy levels in natural abundance
      solid-state (33)S (spin I=3/2) MAS NMR, thereby leading to a significant gain in
      intensity for the central transition (CT). The pair of inversion pulses are
      applied to the satellite transitions for a series of inorganic sulfates, the
      sulfate ions in the two cementitious materials ettringite and thaumasite, and the
      two tetrathiometallates (NH(4))(2)WS(4) and (NH(4))(2)MoS(4). These materials all
      exhibit (33)S quadrupole coupling constants (C(Q)) in the range 0.1-1.0 MHz, with
      precise C(Q) values being determined from analysis of the PT enhanced (33)S MAS
      NMR spectra. The enhancement factors for the WURST and HS elements are quite
      similar and are all in the range 1.74-2.25 for the studied samples, in excellent
      agreement with earlier reports on HS enhancement factors (1.6-2.4) observed for
      other spin I=3/2 nuclei with similar C(Q) values (0.3-1.2 MHz). Thus, a time
      saving in instrument time by a factor up to five has been achieved in natural
      abundance (33)S MAS NMR, a time saving which is extremely welcome for this
      important low-gamma nucleus.

PMID- 18082438
TI  - Gastric dilatation-volvulus associated with diaphragmatic hernia in three cats:
      clinical presentation, surgical treatment and presumptive aetiology.
AB  - Three cats were examined because of acute dyspnoea and sudden abdominal
      enlargement. In all cats, radiographs revealed gastric dilatation-volvulus (GDV)
      and diaphragmatic hernia. Cardiovascular shock and dyspnoea were treated by
      intravenous fluid-therapy, oxygen administration and relief of diaphragmatic
      pressure by means of stomach decompression and in one case placing the patient in
      an inclined position. Gastric decompression was performed by needle
      gastrocentesis, placement of a rhino-gastric tube, or a combination of these.
      Diaphragmatic herniorrhaphy was performed in either case; one cat also underwent
      gastropexy. The immediate postoperative period resolved uneventfully and the cats
      were doing well at follow-up. Feline GDV is a rare event in which diaphragmatic
      hernia may be a predisposing factor.

PMID- 18082437
TI  - Improvement in distance stereoacuity following surgery for intermittent
      exotropia.
AB  - PURPOSE: To evaluate whether distance stereoacuity improves following surgery for
      intermittent exotropia using the Frisby Davis Distance (FD2) and Distance Randot
      stereotests. METHODS: Eighteen patients (median age, 24 years; range, 5 to 68
      years) with intermittent exotropia were prospectively enrolled. Stereoacuity was
      measured pre- and 6 weeks postoperatively using the FD2 and Frisby near tests
      (real depth tests) and Preschool Randot and Distance Randot tests (polaroid
      vectographs). RESULTS: Distance stereoacuity measured with the FD2 improved from
      a median preoperative value of 80 to 40 arcsec postoperatively (p = 0.04) and
      stereoacuity measured with the Distance Randot improved from a median of nil to
      200 arcsec (p = 0.06). In those that had subnormal stereoacuity preoperatively,
      there was even more marked improvement in distance stereoacuity (FD2 median nil
      vs 40 arcsec, p = 0.002; Distance Randot median nil vs 200 arcsec, p = 0.004).
      Near stereoacuity measured with Frisby and Preschool Randot remained unchanged
      pre- to postoperatively (median, 60 and 80 arcsec, respectively). CONCLUSIONS:
      There was improvement in distance stereoacuity measured with both the FD2 and the
      Distance Randot stereotests in patients who underwent surgery for intermittent
      exotropia. The FD2 and Distance Randot may be useful outcome measures in future
      clinical trials of interventions for intermittent exotropia.

PMID- 18082439
TI  - Vacuolar myelopathy: a case report of functional, clinical, and radiological
      improvement after highly active antiretroviral therapy.

PMID- 18082440
TI  - Splenic puncture: diagnostic accuracy and safety in infectious diseases.

PMID- 18082441
TI  - Inhibitory activity and conformation changes of soybean trypsin inhibitors
      induced by ultrasound.
AB  - The inhibitory activities, sulfhydryl bonds and far-UV circular dichroism (CD)
      spectra of Kunitz and Bowman-Birk soybean trypsin inhibitors (KTI and BBTI) were
      measured before and after ultrasound treatments. The differences between KTI and
      BBTI in conformation changes and resistance to ultrasound were observed. The
      secondary structures of KTI were found to be composed of beta-sheet (22.5%), beta
      turn (16.2%) and random coils (61.4%) while that of BBTI composed of only beta
      sheet (52.6%) and random coils (47.4%). KTI lost its inhibitory activity more
      quickly than BBTI, proportionally to the ultrasound amplitudes and sonication
      durations used. Relevant synchronous phenomena observed included the inactivation
      of KTI, significant rise in sulfhydryl content and corresponding conformation
      changes, in which there were dramatic decreases in both beta-turn and random coil
      contents and increase in the beta-sheet structure over the entire sonication
      duration and ultrasonic amplitude scale used by the study. Ultrasound affected
      the activities and conformations of KTI and BBTI by exerting an influence on
      their disulfide bonds. For KTI, up to 55% of inhibitory activity could be
      inactivated, at which about 71.5% of disulfide bonds were altered and the
      [theta]200nm value was changed from native -2545deg cm2 dmol(-1) to -1827 deg cm2
      dmol(-1). Whereas for BBTI, far-UV CD spectra, beta-sheet and random structures
      were barely affected, only about 5.29% of disulfide bonds were found altered and
      the [theta]200nm value was changed only from native -797 deg cm2 dmol(-1) to -700
      deg cm2 dmol(-1). It is concluded that ultrasound inactivates KTI by inducing a
      reduction in the disulfide bonds and then changes the conformations.

PMID- 18082442
TI  - Accuracy of Biodex system 3 pro computerized dynamometer in passive mode.
AB  - A specific experimental design has been developed to determine the accuracy of
      the Biodex system 3 pro dynamometer in passive mode. Five cyclic stretching
      repetitions were imposed to an elastic rubber band at different velocities using
      the dynamometer, and the torque produced was measured using both the dynamometer
      and external force and position sensors. Velocity patterns performed by the
      dynamometer were also characterized and our results show that these patterns were
      reliable (ICC=1.00). The torque measured with the dynamometer and the sensors
      were reliable (ICC=1.00), although significant differences were observed between
      both methods. However, the measured torque standard error was velocity
      independent and was lower than 0.33 Nm. Moreover, regressions between the two
      torque measurements were close to the axes-bisector (r=1.00, slope: 1.01+/-0.01,
      y-intercept: -0.36+/-0.22 Nm). Finally, our results showed decreases in torque
      during the five cycles, but these decreases were not due to the dynamometer. It
      can be concluded that the dynamometer performed valid torque measurements in
      passive mode, and was an accurate tool to determine passive mechanical properties
      of the musculo-articular system. However, some discrepancies between the
      programmed and the measured speed profiles have been observed when approaching
      the speed limit of the system.

PMID- 18082443
TI  - The analysis of the activity of aneugenic chemicals, from cultured cells to
      rodent zygotes: an overview of the Protection of the European Population from
      Aneugenic Chemicals (PEPFAC project).

PMID- 18082444
TI  - Correlation of viral load as determined by real-time RT-PCR and clinical
      characteristics of respiratory syncytial virus lower respiratory tract infections
      in early infancy.
AB  - BACKGROUND: In infants hospitalized for a lower respiratory tract infection (RTI)
      caused by respiratory syncytial virus (RSV), the correlation between viral load
      (VL) and patient clinical characteristics remains to be defined. OBJECTIVES: To
      define this correlation. STUDY DESIGN: prospective study of 47 infants admitted
      to hospital in the period November 2006-May 2007 with a diagnosis of lower RTI.
      Nasopharyngeal aspirates (NPAs) were taken at admission, discharge, and at post
      discharge control visits. VL was quantified by real-time RT-PCR for RSV subgroups
      A and B. RESULTS: Patients with bronchiolitis were compared with young patients
      with lower RTI other than bronchiolitis. Patients with bronchiolitis had a
      significantly lower age than patients with other syndromes, and a significantly
      longer duration of symptoms. Duration of hospitalization was not different in the
      two groups of patients, and was not related to RSV subgroup or viral coinfection.
      A sustained decrease in VL was observed in the general patient population between
      admission, discharge and post-discharge follow-up visits. CONCLUSIONS: (i)
      patients with bronchiolitis were significantly younger than patients with other
      lower RTIs; (ii) symptom duration was significantly longer in patients with
      bronchiolitis; (iii) RSV VL significantly decreased between admission and
      discharge.

PMID- 18082445
TI  - Particle availability controls agglutination in pelagic tintinnids in the
      Southern Ocean.
AB  - Mechanisms of particle selectivity controlling agglutination within the
      agglomerated tintinnid genus Stenosemella spp. Jorgensen were studied during two
      iron fertilisation experiments (EisenEx and EIFEX) conducted in the Southern
      Ocean in austral spring 2000 and late austral summer to early autumn 2004.
      Representative SEM pictures of Stenosemella spp. loricae were taken on the day of
      fertilisation, during the middle and at the end of both experiments. Whereas
      during EisenEx particles used for agglutination were unambiguously dominated by
      coccoliths of Emiliania huxleyi (Lohmann) Hay & Mohle, agglutinated particles
      during EIFEX mainly consisted of broken diatom frustules (BF) of heavily
      silicified species. This observation is supported by the ratio of E. huxleyi
      (Eh)/BF abundances in the water column during both experiments. During EisenEx we
      observed an Eh/BF ratio which was an order-of-magnitude higher compared to the
      EIFEX experiment. Thus, our results clearly indicated that particle availability
      seems to be the driving mechanism in the agglutination of Southern Ocean
      tintinnids. Furthermore, possible implications for the vertical flux of
      agglutinated biogenic particles to deep ocean waters and sediments are discussed.

PMID- 18082446
TI  - An unusual precipitant of tako-tsubo cardiomyopathy.
AB  - A 76-year-old woman presents with acute pulmonary oedema and cardiogenic shock
      10h after elective electrical cardioversion for atrial fibrillation. Her
      echocardiogram shows new wall motion abnormalities with akinesis of the apical
      and mid segments of the left ventricle and her resting ECG contains deep T wave
      inversion and QTc prolongation. Angiography reveals non-occlusive coronary artery
      disease. The echocardiogram on day 6 shows resolution of left ventricular wall
      motion abnormalities and a return to normal systolic function. The diagnosis of
      tako-tsubo cardiomyopathy was made. This is the first report of this condition
      precipitated by electrical cardioversion.

PMID- 18082447
TI  - Thymic cyst causing superior venacava syndrome relieved by mediastinoscopy--a
      rare presentation.
AB  - Superior venacava obstruction is most often caused by intrathoracic malignant
      masses. The commonest cause of benign superior venacava obstruction is fibrosing
      mediastinitis. A thymic cyst causing marked superior venacava obstruction is very
      rare and has not been reported. We hereby present a case of a 40-year-old man
      with such a finding who presented with chest pain and facial congestion.
      Evaluation revealed a mediastinal mass causing marked superior venacaval
      obstruction. He underwent a mediastinoscopy, which showed a cyst. It was drained
      following which there was complete resolution of symptoms post-operatively.
      Histopathology of the lesion confirmed a thymic cyst.

PMID- 18082448
TI  - Cardiac echinococcosis with negative serologies: a report of two cases.
AB  - Cardiac involvement in hydatid cyst disease is uncommon, occurring in
      approximately 2% of hydatid cases. Two cases of cardiac hydatid cysts with
      negative serologic tests are reported herein. In Case 1, the patient underwent
      surgery to remove cysts from the liver and 10 years later presented with symptoms
      and signs of ischaemic heart disease. In Case 2, the patient first underwent
      surgery to remove cysts from the brain and 3 years later for cyst removal from
      the breast. In both cases the diagnosis was established by transthoracic two
      dimensional echocardiography and then confirmed by surgery and histological
      examination. These cases are of particular interest because of the rarity of
      cardiac localisation as a new site of the hydatid cyst after one or more previous
      surgeries for hydatid cyst removal, and stress the need for frequent reevaluation
      to detect new hydatid cyst formation in the heart and elsewhere caused by the
      Echinococcosis organism.

PMID- 18082449
TI  - The curative excision of left ventricular hydatic cyst.
AB  - This cystic mass located in apical region near inferior wall was also
      demonstrated with transoesophageal echocardiography and multislice computerised
      tomography (MCT). The cystic tissue was removed from the myocardium by peeling.
      The cyst was extracted entirely. Ventricular space was washed with hypertonic
      saline serum. Ventriculotomy was closed from inside with dacron patch and
      ventricular geometry was protected successfully. Sewing line was strengthened by
      using teflon stripes externally.

PMID- 18082450
TI  - Mitral valve replacement in patient with absent right superior vena cava, pectus
      excavatum, Marfan syndrome and severe mitral regurgitation.
AB  - Combination of persistent left superior vena cava (PLSVC) draining into right
      atrium via the coronary sinus with a normal right superior vena cava (RSVC) is
      the most common systemic venous anomaly in visceroatrial situs solitus. On the
      other hand, a PLSVC in absence of RSVC is an extremely rare anomaly.
      Cardiovascular abnormalities are frequently encountered in patients with Marfan's
      syndrome but absence of RSVC with PLSVC is not reported in these patients. We
      report on a 52-year-old man with Marfan syndrome, an absence of right superior
      vena cava, severe pectus excavatum and severe mitral regurgitation who underwent
      successful mitral valve replacement. CT scan chest revealed marked cardiac
      deviation to the left associated with severe pectus excavatum, absent right
      superior vena cava and persistent left superior vena cava. During surgery
      replacement of mitral valve was performed through midsternotomy successfully.

PMID- 18082452
TI  - Revolutionizing assessment in a clinical skills environment--a global approach:
      the recorded assessment.
AB  - Assessment is an essential component of education and a key element of the
      student experience. This is never more apparent than in the assessment of student
      nurses competency in practice skills. The use of clinical skills centres to
      facilitate the acquisition of nursing skills continues to gain popularity,
      nonetheless the methods used to develop and assess competency within these
      environments remains diverse with contemporary literature suggesting that the
      objective structured clinical examination (OSCE) is predominantly used. This
      paper presents an innovative approach used within a skills environment to
      summatively assess nursing students at the end of their first year; one that
      seeks to cultivate clinical competency through a process of self-appraisal and
      appreciation of evidence-based literature. The recorded assessment is a unique
      strategy that endeavours to make the learning experience more meaningful for the
      students, through the use of an audio-visual tool and written critique. The
      critique is crucial to the learning process by encouraging the student to adopt a
      critical and holistic view of their practice; essential skills for future
      practitioners.

PMID- 18082451
TI  - Nomograms for predicting survival of patients with newly diagnosed glioblastoma:
      prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3.
AB  - BACKGROUND: A randomised trial published by the European Organisation for
      Research and Treatment of Cancer (EORTC) and the National Cancer Institute of
      Canada (NCIC) Clinical Trials Group (trial 26981-22981/CE.3) showed that addition
      of temozolomide to radiotherapy in the treatment of patients with newly diagnosed
      glioblastoma significantly improved survival. We aimed to undertake an
      exploratory subanalysis of the EORTC and NCIC data to confirm or identify new
      prognostic factors for survival in adult patients with glioblastoma, derive
      nomograms that predict an individual patient's prognosis, and suggest
      stratification factors for future trials. METHODS: Data from 573 patients with
      newly diagnosed glioblastoma who were randomly assigned to radiotherapy alone or
      to the same radiotherapy plus temozolomide in the EORTC and NCIC trial were
      included in this subanalysis. Survival modelling was done in three patient
      populations: intention-to-treat population of all randomised patients (population
      1); patients assigned temozolomide and radiotherapy (population 2, n=287); and
      patients assigned temozolomide and radiotherapy who had assessment of MGMT
      promoter methylation status and who had undergone tumour resection (population 3,
      n=103). Cox proportional hazards models were fitted with and without O6
      methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Nomograms
      were developed to predict an individual patient's median and 2-year survival
      probabilities. No nomogram was developed in the radiotherapy-alone group because
      combined treatment is now the new standard of care. FINDINGS: Independent of the
      MGMT promoter methylation status, analysis in all randomised patients (population
      1) identified combined treatment with temozolomide, more extensive tumour
      resection, younger age, Mini-Mental State Examination (MMSE) score of 27 or
      higher, and no corticosteroid treatment at baseline as independent prognostic
      factors correlated with improved survival outcome. In patients assigned
      temozolomide and radiotherapy (population 2), younger age, better performance
      status, more extensive tumour resection, and MMSE score of 27 or higher were
      associated with better survival. In patients who had tumours resected, who were
      assigned temozolomide and radiotherapy, and who had available MGMT promoter
      methylation status (population 3), methylated MGMT, better performance status,
      and MMSE score of 27 or higher were associated with improved survival. Nomograms
      were developed and are available at http://www.eortc.be/tools/gbmcalculator.
      INTERPRETATION: MGMT promoter methylation status, age, performance status, extent
      of resection, and MMSE are suggested as eligibility or stratification factors for
      future trials in patients with newly diagnosed glioblastoma. Stratifying by MGMT
      promoter methylation status should be mandatory in all glioblastoma trials that
      use alkylating chemotherapy. Nomograms can be used to predict an individual
      patient's prognosis, and they integrate pertinent molecular information that is
      consistent with a paradigm shift towards individualised patient management.

PMID- 18082453
TI  - The N-terminal, TPR-containing domain of the mitotic checkpoint protein BUBR1
      does not bind fatty acids.

PMID- 18082454
TI  - Applications of domain-domain interactions in pathway study.
AB  - The domain combination pair approach is employed to derive putative protein
      domain-domain interactions (DDI) from the protein-protein interactions (PPI)
      database DIP. The results of putative DDI are computed for seven species. To
      determine the prediction performance, putative DDI results are compared with that
      of the database InterDom, where an average matching ratio of about 76% can be
      achieved. Several real PPI pathways are reconstructed based on the predicted DDI
      results. It is found that the pathways could be reconstructed with reasonable
      accuracy. Furthermore, a novel quantity, so called AP-order index, is introduced
      to predict the regulatory order for six PPI pathways. It is found that the AP
      order index is a very reliable parameter to determine the regulatory order of
      PPI.

PMID- 18082455
TI  - Prediction of outcome in isolated congenital diaphragmatic hernia and its
      consequences for fetal therapy.
AB  - Congenital diaphragmatic hernia (CDH) can be diagnosed in the prenatal period
      either as part of other anomalies or as an isolated birth defect. The clinical
      impact of this surgically correctable anatomical defect lies in its impairment of
      lung development. Currently, up to 30% of babies with isolated CDH die from the
      consequences of lung hypoplasia and/or pulmonary hypertension. Antenatal
      prediction of outcome essentially relies on the measurement of lung development
      by the so-called lung area to head circumference ratio (LHR). By expressing
      observed LHR as a proportion of what is normally expected (O/E LHR) at a certain
      time point in gestation, a prediction of outcome can be made. When O/E LHR is
      less than 25% of the normal, postnatal death is very likely. In these cases, an
      antenatal intervention that can improve lung development is currently offered.
      Currently, this is done by percutaneous fetal endoscopic tracheal occlusion
      (FETO) with a balloon at 26-28 weeks, and reversal of occlusion at 34 weeks. The
      feasibility and safety of percutaneous FETO have been established and the
      procedure seems to improve outcome in severe CDH. The lung response to, and
      outcome after, FETO depend on pre-existing lung size respectively gestational age
      at birth. Prenatal decision making can therefore be stratified according to
      measured lung size.

PMID- 18082456
TI  - Semantic memory impairment in temporal lobe epilepsy associated with hippocampal
      sclerosis.
AB  - Episodic memory impairment is a well-recognized feature of mesial temporal lobe
      epilepsy. Semantic memory has received much less attention in this patient
      population. In this study, semantic memory aspects (word-picture matching, word
      definition, confrontation and responsive naming, and word list generation) in 19
      patients with left and right temporal lobe epilepsy secondary to mesial temporal
      sclerosis (MTS) were compared with those of normal controls. Patients with LMTS
      showed impaired performance in word definition (compared to controls and RMTS)
      and in responsive naming (compared to controls). RMTS and LMTS patients performed
      worse than controls in word-picture matching. Both patients with left and right
      mesial temporal lobe epilepsy performed worse than controls in word list
      generation and in confrontation naming tests. Attentional-executive dysfunction
      may have contributed to these deficits. We conclude that patients with left and
      right MTS display impaired aspects of semantic knowledge. A better understanding
      of semantic processing difficulties in these patients will provide better insight
      into the difficulties with activities of daily living in this patient population.

PMID- 18082457
TI  - Toward the development of predictive equations of back muscle capacity based on
      frequency- and temporal-domain electromyographic indices computed from
      intermittent static contractions.
AB  - BACKGROUND CONTEXT: Back muscles capacity is impaired in chronic low back pain
      patients but no motivation-free test exists to measure it. A functional endurance
      test (FET) was used to assess capacity of back muscles using surface
      electromyographic (EMG) indices as outcome measures. PURPOSE: The main objective
      of the present study was to explore the possibility of combining different types
      of EMG indices to predict absolute endurance and strength. STUDY DESIGN/SETTING:
      A cross-sectional study using a repeated measures design in laboratory setting.
      METHODS: Healthy subjects (44 men and 29 women) performed maximal voluntary
      contractions (Strength criterion: extension moment at L5/S1) and a fatigue test
      involving intermittent static extension contractions to exhaustion (Tend
      endurance criterion: time to reach exhaustion). Surface EMG signals were
      collected from four pairs of back muscles. From the first 5 minutes (women) or 10
      minutes (men) of EMG data, frequency- and temporal-domain analyses were applied
      to compute various EMG indices. RESULTS: Strength values ranged from 153 to
      508Nm, whereas Tend values ranged from 3 to 57 minutes across the subjects.
      Gender-specific multiple regression equations were developed, using the retained
      EMG indices from the four electrode sites, to predict Tend (men: R(2)=0.76,
      error=9%; women: R(2)=0.70, error=17%) and Strength (men: R(2)=0.72, error=9%;
      women: R(2)=0.25, error=13%). CONCLUSIONS: It appears to be possible to predict
      the capacity of back muscles using an intermittent and time-limited (submaximal)
      fatigue task. Frequency- and temporal-domain EMG indices were shown to provide
      complementary information in this respect. This FET has potential to better infer
      back muscle capacity for realistic occupational tasks because more specific
      muscle fatigue mechanisms are involved.

PMID- 18082458
TI  - Repair of cervical esophageal perforation using longus colli muscle flap: a case
      report of a patient with cervical spinal cord injury.
AB  - BACKGROUND CONTEXT: Perforation of the esophagus after anterior cervical spine
      surgery is a rare, but well-recognized complication. The management of esophageal
      perforation is controversial, and either nonoperative or operative treatment can
      be selected. PURPOSE: Several reports have described the use of a
      sternocleidomastoid muscle flap for esophageal repair. In this case report, we
      describe a longus colli muscle flap as a substitute for a sternocleidomastoid
      flap in a patient with an esophageal perforation. STUDY DESIGN: Case report.
      PATIENT SAMPLE: A 20-year-old man sustained cervical spinal cord injury, on
      diving and hitting his head against the bottom of a pool. A C6 burst fracture was
      observed with posterior displacement of a bone fragment into the spinal canal.
      The patient exhibited complete paralysis below the C8 spinal segment level.
      METHODS: The patient underwent subtotal corpectomy of the sixth cervical vertebra
      with the iliac bone graft and augmented posterior spinal fixation (C5-7) with
      pedicle screws. After the primary operation, the patient showed signs of
      infection such as throat pain, a high fever, and osteolytic change of the grafted
      bone by cervical radiograph. A second operation was performed to replace the
      graft bone using fibula. On the day after the operation, food residue was
      confirmed in the suction drainage tube, suggesting esophagus perforation. A third
      operation was immediately performed to confirm and treat esophagus perforation,
      although apparent esophageal perforation could not be detected at the second
      operation. Because the erosion around the perforation of the esophageal posterior
      wall was extensive, a longus colli muscle flap transposition was accordingly
      performed into the interspace between the esophageal posterior wall and the
      grafted bone in addition to simple suturing of the perforation. RESULTS: Neither
      high fever nor pharyngeal pain has recurred at latest follow-up, 5 years after
      surgery. CONCLUSIONS: To the best of our knowledge, this is the first report
      concerning the use of a longus colli muscle flap for esophageal perforation after
      anterior cervical spine surgery.

PMID- 18082459
TI  - Improving accuracy and reducing errors in spinal surgery--a new technique for
      thoracolumbar-level localization using computer-assisted image guidance.
AB  - BACKGROUND CONTEXT: The accurate identification of the correct vertebral level
      during surgery remains problematic and still accounts for a significant
      percentage of litigation. The ideal technique for spinal-level localization would
      have the following characteristics: easy availability in the operating theater,
      lowest-possible radiation exposure for the professional team and the patient,
      simple technique which is easily reproducible at any time during surgery, usable
      with all forms of spine surgery, permanently recordable, able to be used
      throughout the spine, able to be easily checked by nonspecialist members of the
      team, and accurate. PURPOSE: We describe a new technique for thoracolumbar-level
      localization, based on these principles, which uses computer-assisted image
      guidance. STUDY DESIGN: Surgery technique development in clinical practice.
      METHODS: The technique uses standard image intensifier radiology with FluoroNav
      Spine or FluoroNav MAST software on the StealthStation computer-assisted surgery
      system. (Medtronic Navigation, Louisville, ed) Adjacent, contiguous, images are
      taken in the desired plane from the reference area of the lumbosacral junction to
      the general area of operative interest. These images can then be displayed
      simultaneously on the computer screen. Use of the probe extension feature allows
      counting, external to the skin and drapes, from the reference level to the level
      of interest at any time without additional radiation exposure. Standard
      navigation can then be undertaken at the operative level. RESULTS: This technique
      has been used in 17 cases, all of which have been undertaken in the mid- or low
      thoracic and lumbar regions where the operative level is not visible on the same
      image intensifier image as the lumbosacral junction. All cases have undergone
      postoperative radiology to check the surgery level and no cases of incorrect
      level of surgery have occurred. No accuracy errors have developed during surgery
      and no complications from the reference arc have occurred. CONCLUSIONS: This
      technique is indicated for level localization in the spine where the operative
      level cannot be visualized on the same fluoroscopy field of view as the reference
      level. It has a relative contraindication in the upper thoracic spine, in the
      very obese, and in the presence of osteoporosis where fluoroscopic imaging is
      difficult, although we postulate a technique using preoperative computed
      tomography (CT) to overcome these difficulties. This technique satisfies a number
      of criteria for the "ideal technique" and has advantages over current methods. A
      number of caveats are level localization and the use of this technique are
      presented.

PMID- 18082460
TI  - Feasibility of a stem cell therapy for intervertebral disc degeneration.
AB  - BACKGROUND CONTEXT: Different strategies to supplement/replenish the disc cell
      population have been proposed. Recently, adult stem cells have shown promise as a
      cell source for a variety of tissue engineering and cell therapy applications. A
      stem cell can renew itself through cell division and can be induced to develop
      into many different specialized cell types. Moreover, stem cells have shown
      ability to migrate and engraft within various tissues, as well as to exert
      stimulatory effects on other cell types through various mechanisms (eg, paracrine
      effects, cell-cell interactions). These characteristics make stem cells worthy of
      investigation as a source of cells for intervertebral disc (IVD) tissue
      engineering and cell therapy. PURPOSE: To determine feasibility of a stem cell
      therapy of IVD degeneration. STUDY DESIGN: In vitro studies of adult human cells
      to examine interactions between nucleus pulposus cells (NPCs) and mesenchymal
      stem cells (MSCs) at different ratios in 3-D pellet culture. In vivo studies of
      healthy adult rabbit discs injected with allogenic adult rabbit MSCs to examine
      stem cell survival and engraftment in living disc tissue. METHODS: In vitro
      study: Human NPCs were cocultured with human MSCs in different ratios (75:25,
      50:50, 25:75) for 2 weeks in pellet culture, for comparison with pure NPC (100:0)
      and pure MSC (0:100) pellet cultures. Proteoglycan synthesis rate and
      glycosaminoglycan (GAG) content were measured by radioactive sulfate
      incorporation and dimethylmethylene blue assay, respectively. In vivo study: MSCs
      were isolated from the bone marrow of a New Zealand White (NZW) rabbit,
      retrovirally transduced with the lacZ marker gene, and injected into the nucleus
      pulposi of the L2-3, L3-4, and L4-5 lumbar discs of 12 other NZW rabbits. Three
      rabbits each were sacrificed at 3, 6, 12, or 24 weeks after cell implantation,
      and X-Gal staining was done to assess survival and localization of MSCs in the
      disc tissues. RESULTS: In vitro study: the 75:25 and 50:50 NPC:MSC cocultures
      yielded the greatest increases in extracellular matrix (ECM) production. In vivo
      study: MSCs were detected in histological sections of rabbit discs up to 24 weeks
      after allogenic stem cell implantation, without evidence of systemic illness in
      the recipient rabbits. The 24-week results in particular suggested the
      possibility of stem cell migration and engraftment into the inner annulus
      fibrosus. CONCLUSIONS: These encouraging results support feasibility of a stem
      cell therapy approach toward supplementation/replenishment of IVD cells and
      synthesis/maintenance of a more functional ECM in a degenerated disc. Moreover,
      the in vivo results demonstrate that transplanted MSCs survive and successfully
      engraft into the IVD tissue, and are effective vehicles for exogenous gene
      delivery to the IVD--thus there appear to be multiple mechanisms whereby stem
      cells might able to confer therapeutic effects in a stem cell therapy of IVD
      degeneration.

PMID- 18082461
TI  - Degenerative lumbar spinal stenosis: an evidence-based clinical guideline for the
      diagnosis and treatment of degenerative lumbar spinal stenosis.
AB  - BACKGROUND CONTEXT: The objective of the North American Spine Society (NASS)
      evidence-based clinical guideline for the diagnosis and treatment of degenerative
      lumbar spinal stenosis (DLSS) is to provide evidence-based recommendations to
      address key clinical questions surrounding the diagnosis and treatment of DLSS.
      The guideline is intended to reflect contemporary treatment concepts for
      symptomatic DLSS as reflected in the highest quality clinical literature
      available on this subject as of April 2006. The goals of the guideline
      recommendations are to assist in delivering optimum, efficacious treatment, and
      functional recovery from this spinal disorder. PURPOSE: To provide an evidence
      based tool that assists practitioners in improving the quality and efficiency of
      care delivered to patients with DLSS. STUDY DESIGN/SETTING: Evidence-based
      clinical guideline. METHODS: This report is from the Spinal Stenosis Work Group
      of the NASS Clinical Guidelines Committee. The work group comprised medical,
      diagnostic, interventional, and surgical spinal care specialists, all of whom
      were trained in the principles of evidence-based analysis. In the development of
      this guideline, the work group arrived at a consensus definition of a working
      diagnosis of lumbar spinal stenosis by use of a modification of the nominal group
      technique. Each member of the group formatted a series of clinical questions to
      be addressed by the group and the final list of questions agreed on by the group
      is the subject of this report. A literature search addressing each question and
      using a specific literature search protocol was performed on English language
      references found in MEDLINE, EMBASE (Drugs and Pharmacology), and four
      additional, evidence-based, databases. The relevant literature to answer each
      clinical question was then independently rated by at least two reviewers using
      the NASS-adopted standardized levels of evidence. An evidentiary table was
      created for each of the questions. Any discrepancies in evidence levels among the
      initial raters were resolved by at least two additional members' review of the
      reference and independent rating. Final grades of recommendation for the answer
      to each clinical question were arrived at in face-to-face meetings among members
      of the work group using the NASS-adopted standardized grades of recommendation.
      When Levels I to IV evidence was insufficient to support a recommendation to
      answer a specific clinical question, expert consensus was arrived at by the work
      group through the modified nominal group technique and is clearly identified as
      such in the guideline. RESULTS: Eighteen clinical questions were asked,
      addressing issues of prognosis, diagnosis, and treatment of DLSS. The answers to
      these 18 clinical questions are summarized in this document along with their
      respective levels of evidence and grades of recommendation in support of these
      answers. CONCLUSIONS: A clinical guideline for DLSS has been created using the
      techniques of evidence-based medicine and using the best available evidence as a
      tool to aid both practitioners and patients involved with the care of this
      disease. The entire guideline document including the evidentiary tables,
      suggestions for future research, and all references is available electronically
      at the NASS Web site (www.spine.org) and will remain updated on a timely
      schedule.

PMID- 18082462
TI  - Uncorrected sagittal plane imbalance predisposes to symptomatic instrumentation
      failure.
AB  - BACKGROUND CONTEXT: Elucidation of the factors responsible for symptomatic
      failure of spinal instrumentation has been a keen interest for many
      investigators. PURPOSE: To quantitate the number of symptomatic instrumentation
      failures (SIFs) encountered during a 2-year period. The effect of sagittal plane
      imbalance (corrected or uncorrected) on the rate of SIF was evaluated. STUDY
      DESIGN: Retrospective evaluation of all patients requiring spinal instrumentation
      to determine which factors predispose toward instrumentation failure. PATIENT
      SAMPLE: All patients requiring spinal instrumentation over a 2-year period were
      retrospectively studied. OUTCOME MEASURES: Sagittal plane imbalance pre- and
      postoperatively was determined using Cobb angle analysis on plain X-rays. SIF was
      defined as screw back-out and/or breakage, pseudarthrosis, cage migration, or rod
      disconnection in patients with concordant symptoms. Asymptomatic patients did not
      demonstrate instrumentation failure on the routine postoperative X-rays. METHODS:
      Of the 355 patients who fit the criteria, 47 patients presented with either
      idiopathic or secondary sagittal plane deformity preoperatively. Additionally,
      long-segment fixation, smoking, age, and fixation across junctional segments were
      evaluated as risk factors for SIF. RESULTS: Of the 47 patients with sagittal
      plane deformity, 40 patients (85%) achieved correction demonstrated on
      postoperative radiographs whereas in 7 (15%), the sagittal plane imbalance was
      not corrected. Of these seven cases, five suffered instrumentation failure
      (failure rate 71.5%) versus no instrumentation failures (failure rate 0%) for the
      remaining 40 patients. SIF was demonstrated in 10 patients overall (failure rate
      of 2.8%). There was no correlation found between factors such as age, indications
      for surgery, or long-segment fixation, and instrumentation failure. CONCLUSIONS:
      Failure to correct sagittal plane deformity intraoperatively predisposes patients
      to SIF regardless of age, level of surgery, or indication of surgery.

PMID- 18082463
TI  - Biomechanical comparison of different anchors (foundations) for the pediatric
      dual growing rod technique.
AB  - BACKGROUND CONTEXT: Children with early onset scoliosis benefit from early
      operative treatment with dual growing rods as they provide an "internal brace"
      for the spine and allow curve correction and sequential lengthenings to maximize
      thoracic cage development. The foundations that provide anchor points for the
      dual growing rods may incorporate hooks, screws, or a hybrid construct. It is
      unclear how stable different types of foundation constructs are with regard to
      pullout. PURPOSE: This study was to determine the differences in stability
      between four foundation configurations used in the pediatric dual growing rod
      technique. Eight porcine spines were sectioned and randomly assigned to one of
      four foundation groups: 1) hook-hook with cross-link; 2) hook-screw with cross
      link; 3) screw-screw with cross-link; and 4) screw-screw without cross-link.
      After instrumentation, biomechanical pullout tests were conducted. Ultimate
      failure loads, modes of failure, and level of instrumentation were analyzed.
      STUDY DESIGN/SETTING: Controlled in vitro laboratory investigation. RESULTS:
      Screw-screw with cross-link constructs demonstrated the greatest failure load but
      this was not statistically significant compared with the screw-screw without
      cross-link constructs. Both screw-screw constructs were statistically stronger
      than either construct containing hooks. There was no difference between the hook
      screw and hook-hook constructs that was statistically significant. Hook
      containing constructs sustained higher failure loads in lumbar versus thoracic
      vertebrae. CONCLUSIONS: A foundation composed of four pedicle screws implanted in
      two adjacent vertebral bodies provides the strongest construct in pullout
      testing. A cross-link does not seem to enhance fixation. Hook constructs are
      stronger in lumbar versus thoracic laminae.

PMID- 18082464
TI  - Posterior spinal fusion using a pedicle nail system with polymethylmethacrylate
      in a paraplegic patient after vertebral collapse caused by osteoporosis.
AB  - BACKGROUND CONTEXT: Because posterior decompression and fusion for vertebral
      collapse in an osteoporotic spine sometimes results in a pullout of the pedicle
      screw. Several authors reported that fixation of pedicle screws in severely
      osteoporotic bone could be improved by inserting polymethylmethacrylate (PMMA)
      into the hole before inserting the screw. However, pedicle screws were not
      designed to be used with PMMA. PURPOSE: To report a patient with vertebral
      collapse who were treated using a novel-concept, pedicle nail using with PMMA.
      STUDY DESIGN: Case report. METHODS: The patient was a 74-year-old female who
      experienced back pain after some heavy lifting 3 months before. She was laid up
      for 2 months because of the back pain and weakness of her lower legs. Radiographs
      and magnetic resonance imaging showed vertebral collapse and neural severe
      compression from the posterior wall of vertebra T12. The pedicle nail consists of
      an outer sheath with evenly spaced holes and an internal, removable, threaded
      component. The outer sheath and the internal component were connected before
      insertion. The pedicle nail attaches to and is bound by the PMMA through the
      holes of the outer sheath. We performed a T11-L1 posterior fusion and laminectomy
      using the pedicle nail, and we used a hydroxyapatite block to perform a
      transpedicular vertebroplasty of T12. RESULTS: Bone union was observed on a
      lateral radiograph without pedicle nail loosening. CONCLUSIONS: The authors
      speculate that posterior spinal fusion and vertebroplasty using the pedicle nail
      will be a reasonable choice for delayed paraplegia after osteoporotic vertebral
      fracture.

PMID- 18082465
TI  - Isolated C3-C4 disc herniations present as a painless myelopathy.
AB  - BACKGROUND CONTEXT: Cervical disc herniations at the C3-C4 level are distinctly
      uncommon. The authors present the first case series of isolated C3-C4 disc
      herniations presenting with myelopathy. PURPOSE: To elucidate a rare presentation
      of the uncommon C3-C4 disc herniation. STUDY DESIGN: Case series. PATIENT SAMPLE:
      The four patients who presented with myelopathy caused by isolated C3-C4 disc
      herniations, at the spine unit, Vancouver General Hospital between 1999 and 2005.
      OUTCOME MEASURE: Improvement in neurological status. METHODS: We retrospectively
      reviewed the files of the patients. The clinical features and outcome of surgery
      were assessed. RESULTS: The C3-C4 disc herniation can present as with no or mild
      pain, and hand numbness was a prominent symptom. Early recognition and treatment
      led to favorable outcome. CONCLUSIONS: Myelopathy is rarely caused by a C3-C4
      disc herniation. This etiology may be underdiagnosed but has a more favorable
      outcome in those cases where rapid diagnosis is followed by spinal cord
      decompression.

PMID- 18082466
TI  - Bone morphogenetic protein-7 protects human intervertebral disc cells in vitro
      from apoptosis.
AB  - BACKGROUND CONTEXT: Disc degeneration includes dysfunction and loss of disc cells
      leading to a decrease in extracellular matrix (ECM) components. Apoptosis has
      been identified in degenerated discs. Bone morphogenetic protein-7 (BMP-7) has
      been reported to stimulate ECM synthesis in the intervertebral disc (IVD), but
      its effect on disc cell viability is unknown. PURPOSE: To investigate whether BMP
      7 can protect disc cells from programmed cell death while enhancing ECM
      production. STUDY DESIGN: An in vitro study to examine the effect of BMP-7 on
      apoptosis of IVD cells. METHODS: Human nucleus pulposus (NP) cells were cultured
      in monolayer, and human recombinant pure BMP-7 (rhBMP-7) was added to the medium
      when the cells were in the second passage. Thereafter, apoptosis was induced by
      either tumor necrosis factor-alpha (TNF-alpha) or hydrogen peroxide (H(2)O(2)).
      Cellular apoptosis was evaluated by terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling assay and caspase-3 activity. ECM synthesis was
      assessed by immunofluorescence for collagen-2 and aggrecan. To study the
      possibility of bone induction by rhBMP-7 in disc cells, alkaline phosphatase
      activity and Alizarin red-S staining were evaluated. RESULTS: Apoptosis was
      induced by both TNF-alpha and H(2)O(2). Addition of rhBMP-7 resulted in
      inhibition of the apoptotic effects caused by both inducers. Further, BMP-7
      decreased caspase-3 activity. In the presence of BMP-7, ECM production was
      maintained by the cells despite being in an apoptotic environment. No
      osteoblastic induction of the disc cells was seen. CONCLUSIONS: BMP-7 was
      demonstrated to prevent apoptosis of human disc cells in vitro. One of the
      antiapoptotic effects of BMP-7 on NP cells might be a result of its inactivation
      of caspase-3. Collagen production was maintained by addition of rhBMP-7 in an
      apoptotic environment.

PMID- 18082468
TI  - Participatory design with children in the development of a support system for
      patient-centered care in pediatric oncology.
AB  - Developing software for children with severe illness poses a number of design
      challenges. In this paper we describe participatory design methods used in the
      development of SISOM, a support system for children with cancer age 7-12 to help
      children elicit and report their symptoms/problems in a child-friendly, age
      adjusted manner, and to assist clinicians at the point of care in addressing and
      integrating children's reported symptoms and problems in patient care. The
      particular design challenges in the development of a clinical support tool for
      seriously ill children are described, followed by the participatory design
      techniques we used to meet these challenges. Healthy children and children with
      cancer participated actively in different stages of the design process. We
      describe how children contributed to the graphical design of the system's
      interface; selection of understandable, child-friendly terms used in the system;
      iconic and graphical representations; and its usability. The methods applied
      helped us to significantly improve and adapt SISOM to children's cognitive and
      emotional developmental stage. Working with children as partners in the design
      also provided important insights into the role children can play in participatory
      design that may be helpful for other system developers who wish to design support
      applications for ill children. Children had very creative design ideas that
      considerably improved the software. However, system development for seriously ill
      children also requires psychological and pedagogical insights and design and
      usability expertise. This limits the role children can play as full design
      partners.

PMID- 18082467
TI  - Traumatic spondyloptosis resulting from high-energy trauma concurrent with a
      tonic-clonic seizure.
AB  - BACKGROUND CONTEXT: Traumatic lumbosacral dislocation injuries are rare, high
      energy injuries that are challenging to surgically manage. PURPOSE: To report a
      patient with a traumatic spondyloptosis of L5 on S1 as a result of bilateral
      pedicle fractures of L4 and L5 occurring during a motor vehicle accident,
      concurrent with a tonic-clonic seizure. The mechanism and treatment of the injury
      are discussed. STUDY DESIGN: Clinical case report and literature review. METHODS:
      A staged circumferential fusion was performed with posterior reduction of L5 to
      the sacrum and instrumentation and fusion from L2 to the pelvis, followed 12 days
      later by anterior diskectomies and arthrodesis from L3 to S1. RESULTS: Near
      anatomic reduction and solid fusion were obtained and maintained at 3-year follow
      up. The patient remained neurologically intact in all lumbosacral roots
      throughout the course of treatment. CONCLUSIONS: The injury pattern described is
      quite rare. This case of multilevel, bilateral pedicle fracture with traumatic L5
      S1 spondyloptosis was successfully treated by circumferential reduction and
      arthrodesis without neurological injury.

PMID- 18082469
TI  - Early and late effects of cardiac resynchronization therapy on force-frequency
      relation and contractility regulating gene expression in heart failure patients.
AB  - BACKGROUND: Heart failure is associated with a reduction in left ventricular (LV)
      contractility as evidenced by a blunted force-frequency response (FFR) and
      downregulation of contractility regulating genes. OBJECTIVE: This study sought to
      investigate whether cardiac resynchronization therapy (CRT) is capable of
      reversing the blunted FFR and the downregulation of contractility regulating
      genes. METHODS: Twenty heart failure patients underwent echocardiographic
      examination during incremental AAI and DDD-CRT pacing at 70, 90, and 110
      beats/min, immediately after and 4 months after CRT implantation. The FFR was
      determined from the ratio of the LV systolic pressure/end systolic volume index
      at given heart rate. In a subgroup of 6 patients with idiopathic dilated
      cardiomyopathy, serial LV dP/dtmax was invasively measured during both pacing
      modes and serial LV endomyocardial biopsies were taken to measure sarcoplasmatic
      reticulum calcium ATPase 2alpha (SERCA2alpha), phospholamban (PLN), sarcolemmal
      sodium calcium exchanger (NCX), beta1-adrenoreceptor (beta1-AR), and apelin (APL)
      gene expression using reverse-transcriptase polymerase chain reaction. RESULTS:
      Acutely, DDD-CRT pacing was associated with a decrease in dyssynchrony (P <.01)
      and increase in diastolic filling time (P <.01) at all heart rates paralleled by
      an upward shift of the FFR (P <.01) without force-frequency amplification. A
      greater upward shift of the FFR was noticed during DDD-CRT as compared with AAI
      (P <.01) after 4 months. In addition, CRT was associated with a significant force
      frequency amplification at follow-up as evidenced from the steeper slope of the
      FFR relationship (P = .039). This was associated with a significant upregulation
      of SERCA2alpha P = .01), PLN (P = .01), their ratio (P = .01), ratio of SERCA/NCX
      (P = .02), beta1-AR (P = .03), and APL (P = .01) mRNA levels. CONCLUSION: CRT is
      associated with an acute upward shift in the FFR without force-frequency
      amplification related to restored synchronicity and increased filling time of the
      LV. Only chronic CRT is associated with force-frequency amplification in parallel
      to upregulation of contractility regulating genes.

PMID- 18082470
TI  - A comparison of methods and results in recruiting white and black women into
      reproductive studies: the MMC-PSU cooperative center on reproduction experience.
AB  - Establishing a holistic approach for the enrollment of subjects into clinical
      trials that includes strategies for the recruitment of non-traditional and
      minority populations has been an elusive task. The existence of such a design,
      that is understood and embraced by investigators and the target communities,
      would streamline the current level of commitment of time, energy and resources.
      This is necessary to successfully encourage individual and community
      participation in research studies. The Center for Research in Reproduction at
      Meharry set out to recruit a large number of African American women volunteers of
      reproductive age into clinical trials. The experience, of recruiting volunteers
      from the African American community for clinical trials in the Meharry Medical
      College/Pennsylvania State University (MMC/PSU)'s Cooperative Center for Research
      in Reproduction at Meharry, is presented.

PMID- 18082471
TI  - Mitochondrial DNA variant A4917G, smoking and spontaneous preterm birth.
AB  - Spontaneous preterm birth (PTB; <37 weeks gestation) is a major risk factor for
      neonatal morbidity and mortality. The exact cause of PTB is unknown but oxidative
      stress may play an important role. Genetic studies have recently begun to
      elucidate the role of genetic variation in PTB but these studies have overlooked
      the mitochondrial genome/gene(s) as a plausible PTB candidate. In the present
      study, we sought to document association between nonsynonymous mitochondrial DNA
      (mtDNA) variants A4917G, G10398A and T4216C and PTB. We performed a case (PTB;
      <36 weeks gestation)-control (normal term) analysis of these mtDNA markers and
      examined their potential interaction with smoking in PTB. A sample of 422
      pregnant Caucasian women (220 preterm and 202 terms) was examined for
      association. Haplogroup T marker A4917G was identified as a possible candidate
      for association with PTB after adjusting for smoking (OR=1.99 [95% CI 0.93-4.24])
      as was T4216C (OR=1.63 [95% CI 0.93-2.83]). No significant multi-locus
      interactions or interactions with other environmental variables were observed.
      Our data, although preliminary, support the hypothesis that mitochondrial genome
      polymorphisms may play a significant role in PTB through an interaction with
      smoking.

PMID- 18082472
TI  - A fast method for the quantification of methylamine in fermentation broths by gas
      chromatography.
AB  - The objective of this study was to develop a method for the quantitative analysis
      of the methylamine concentration in fermentation broths of Hyphomicrobium
      zavarzinii ZV 580 cultures. For this purpose an established method for the
      quantification of free amino acids in such matrices was adapted and validated.
      The detection limit was 10 microM, the calibration curve showed good linearity
      (R2=0.9998) in the concentration range between 0.1 and 8 mM. The standard
      deviation of the injection-to-injection reproducibility (n=10) of the retention
      coefficient was <1%, that of the peak area<5%. In case of the sample-to-sample
      reproducibility (n=8), the standard deviation was <5% for the retention
      coefficient and <10% for the peak area. The validated method was successfully
      applied for monitoring a fed-batch bioprocess (starting volume: 8L, initial
      methylamine hydrochloride concentration: 10 mM) producing a dye-linked
      formaldehyde dehydrogenase in H. zavarzinii ZV 580.

PMID- 18082473
TI  - Study comparing oesophageal capsule endoscopy versus EGD in the detection of
      varices.
AB  - BACKGROUND: Endoscopic screening and surveillance of cirrhotic patients for
      oesophageal varices is advocated before initiation of prophylactic therapy for
      prevention of the first variceal haemorrhage. AIMS: To compare the diagnostic
      yield of oesophageal capsule endoscopy (ECE) with Esophagogastroduodenoscopy
      (EGD) for detecting and grading oesophageal varices and to determine patient
      tolerance for each procedure. PATIENTS: Twenty consecutive cirrhotic patients
      scheduled for EGD were enrolled in the study. METHODS: Patients underwent ECE
      followed by EGD. Patients completed a visual analogue scale after each procedure,
      assessing level of anxiety, pain, overall satisfaction, and willingness to repeat
      each procedure. RESULTS: On EGD, 19/20 patients had oesophageal varices. ECE
      detected varices in 13/19 (68% sensitivity). ECE identified nine out of ten
      varices rated grade II or higher on EGD. The post-study analogue scale showed a
      greater level of anxiety before EGD (avg. 2.75/10) versus ECE (avg. 1.5/10).
      CONCLUSIONS: ECE may be used in the assessment of EV. It appears to have more
      discordance with EGD when evaluating smaller varices. The minimal discomfort,
      lack of sedation, and decreased risk make ECE a possible substitute to EGD in
      patients unable or unwilling to undergo EGD.

PMID- 18082474
TI  - Esophageal impedance-pH monitoring.
AB  - Classical techniques like endoscopy and esophageal pH-metry are routinely used to
      study patients with symptoms related to gastroesophageal reflux disease (GERD).
      Although these techniques have been useful over the years both for diagnosis and
      therapeutic guidance, there are still many patients with typical or atypical GERD
      symptoms with normal endoscopy and pH-metry that do not respond adequately to
      antisecretory therapy. Ambulatory esophageal impedance-pH monitoring is a new
      technique that can be used to evaluate all types of gastroesophageal reflux,
      achieving higher rates of sensitivity and specificity than standard techniques.
      This review describes esophageal impedance-pH monitoring, summarizing the current
      literature on validation studies and clinical application.

PMID- 18082475
TI  - Severe hypokaliemia and metabolic alkalosis in a Crohn's disease patient after
      budesonide treatment: evidence for intestinal secretion of potassium.

PMID- 18082476
TI  - Relationship between nonalcoholic fatty liver disease prevalence and visceral fat
      in obese adolescents.
AB  - BACKGROUND: Visceral adiposity is the major risk factor for paediatric
      nonalcoholic fatty liver disease. AIMS: Determine the prevalence of nonalcoholic
      fatty liver disease according to the visceral fat quartile. SUBJECTS: 181 obese
      adolescents including 113 girls (16.58+/-1.56 years) and 68 boys (16.87+/-1.62
      years) were evaluated. METHODS: The inclusion criteria were obesity and post
      pubertal stage of Tanner. Visceral fat of obese adolescents was distributed in
      quartiles after ultrasound nonalcoholic fatty liver disease diagnosis. RESULTS:
      Nonalcoholic fatty liver disease prevalence was 45.30%. It was observed that
      62.07% and 76.47% of girls and boys with nonalcoholic fatty liver disease were
      found in the 4th quartile. In a multivariate logistic analysis it was observed
      that only visceral fat remained statistically significant, every 1cm increase in
      visceral fat was associated with a 1.97 fold (95% CI 1.06-3.66) in boys and 2.08
      fold (95% CI 1.38-3.13) in girls increased risk to develop nonalcoholic fatty
      liver disease. Indeed it was verified a positive correlation between visceral
      fat, body mass index, insulin levels, homeostasis model assessment insulin
      resistance index and steatosis degree. CONCLUSIONS: Our findings suggested that
      the expansion of visceral fat was a determinant factor to increase nonalcoholic
      fatty liver disease prevalence and the visceral fat measured by ultrasound might
      be a good predictor to identify risk for nonalcoholic fatty liver disease in
      obese adolescents. It was confirmed by a stronger correlation between visceral
      fat and body mass index.

PMID- 18082477
TI  - Assessment of tissue scaffold degradation using electrochemical techniques.
AB  - Degradation of a commercially available collagen-glycosaminoglycan dermal
      equivalent matrix was studied using electrochemical techniques. Degradation was
      accelerated by exposure to gamma radiation followed by storage at elevated
      temperatures or exposure to enzymes. The time-dependent diffusion of a small,
      electrochemically active, molecular probe, potassium ferrocyanide, through the
      matrix was monitored via changes in the oxidation peak currents of cyclic
      voltammograms. These measurements were made using a two-compartment diffusion
      chamber with the sample positioned well away from the working electrodes and a
      single-compartment electrode cell where the matrix was in direct contact with the
      working electrode. The relative merits of these two approaches are considered.
      Regardless of the approach chosen, amperometry appears well suited to monitoring
      progressive diffusivity changes through mechanically weak porous structures
      subject to different solution environments.

PMID- 18082478
TI  - Transverse thoracodorsal artery perforator flaps: experience with 31 free flaps.
AB  - The conventional design of free thoracodorsal artery perforator (TDAP) flaps is
      orientated vertically along the long axis of the latissimus dorsi muscle, i.e.
      along the course of the descending branch of the thoracodorsal artery. However,
      this method does not consider perforators derived from the transverse branch of
      the thoracodorsal artery, and leaves a long scar that runs perpendicular to the
      relaxed skin tension line. Accordingly, scar widening and hypertrophy are
      frequently encountered problems. From April 2004 to December 2005, 31 free TDAP
      flap transfers were performed in 29 patients for reconstruction of the lower
      extremity (16 flaps), head and neck (12 flaps), and upper extremity (three
      flaps). Flap long axes were laid transversely following the relaxed skin tension
      line and paddles were designed to include proximal perforators from both branches
      of the thoracodorsal artery. Flap sizes ranged from 7x5 cm to 22x12 cm with a
      mean thickness of 7.5mm (range 3-13 mm). Among the 40 perforators employed as
      pedicles, 34 were derived from the descending branch and six were from the
      transverse branch of the thoracodorsal artery. Except for a single case of total
      flap loss, the other flaps were successfully transferred. Donor scars ranged from
      6 to 28 mm in width after a minimum follow-up period of 10 months. The transverse
      design may be preferred whilst planning free TDAP flap transfer, because the
      surgeon has a wider choice of perforators and the final donor scar has a less
      disfiguring appearance.

PMID- 18082479
TI  - Further reporting of tibial stress fractures complicating free fibula grafts.

PMID- 18082480
TI  - An obesity paradox in acute heart failure.

PMID- 18082481
TI  - The pathophysiology of acute heart failure--it is a lot about fluid accumulation.

PMID- 18082482
TI  - Establishing the effectiveness of coronary intervention for acute myocardial
      infarction.

PMID- 18082483
TI  - The pathophysiology of acute heart failure--is it all about fluid accumulation?
AB  - Despite significant advancement in chronic heart failure (HF), no breakthroughs
      have occurred in the last 2 decades in our understanding of the pathophysiology,
      classification, and treatment of acute HF (AHF). Traditional thinking, which has
      been that this disorder is a result of gradual fluid accumulation on a background
      of chronic HF, has been called into question by recent large registries enrolling
      less selected patient populations. It is increasingly recognized that many
      patients with this syndrome are elderly, have relatively preserved ejection
      fraction, and have mild or no preexisting chronic HF. In this review, we propose
      2 primary subtypes of AHF: (1) acute decompensated cardiac failure, characterized
      by deterioration of cardiac performance over days to weeks leading to
      decompensation; and (2) acute vascular failure, characterized by acute
      hypertension and increased vascular stiffness. Registry data suggest that the
      latter is the more common form of AHF in the general population, although the
      former is often overrepresented in studies focused in academic tertiary care
      centers. Regardless of the clinical subtype, a variety of pathophysiologic
      mechanisms may play a role in this disorder, many of which remain poorly
      understood. In this review, we describe current understanding of the
      pathophysiology of AHF, including a critical evaluation of the data supporting
      both traditional and novel mechanisms, and suggest a framework for integrating
      these mechanisms into an overall model of AHF.

PMID- 18082484
TI  - Rationale and design of the Trial of Routine ANgioplasty and Stenting After
      Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER
      AMI).
AB  - BACKGROUND: Most patients with ST-elevation myocardial infarction present to
      hospitals without percutaneous coronary intervention (PCI) facilities and receive
      fibrinolysis. The role of routine early PCI after fibrinolysis, using stents and
      contemporary pharmacotherapy, has not been studied in a large adequately powered
      randomized trial. OBJECTIVE: To compare a pharmacoinvasive strategy of transfer
      for routine PCI within 6 hours after fibrinolysis with standard treatment after
      fibrinolysis (including predefined criteria for rescue PCI and delayed cardiac
      catheterization for patients who do not require rescue PCI). METHODS: A total of
      1200 patients with high-risk ST-elevation myocardial infarction presenting to non
      PCI centers will be randomized to a pharmacoinvasive strategy (transfer for
      routine PCI within 6 hours of fibrinolysis) or to standard treatment after
      fibrinolysis. The primary end point is the 30-day composite of death,
      reinfarction, recurrent ischemia, heart failure, or shock. RESULTS: More than 900
      patients have been enrolled as of April 2007. An interim safety analysis of the
      first 536 patients demonstrated no safety concerns. Enrolment is expected to be
      completed in late 2007. CONCLUSIONS: This study will provide important data on
      whether routine early PCI within 6 hours after fibrinolysis is safe and superior
      to the standard treatment of fibrinolysis with rescue PCI or delayed cardiac
      catheterization.

PMID- 18082485
TI  - Rationale, design, and baseline characteristics for a large international trial
      of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial
      (Outcome Reduction with an Initial Glargine Intervention).
AB  - AIMS: Impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and
      diabetes arise due to insufficient insulin secretion and are risk factors for
      cardiovascular (CV) events. Thus, targeting normal fasting glucose levels with
      insulin may reduce CV events. Previous studies suggest that omega-3 fatty acid
      supplements may reduce CV death; however, their effect in high-risk dysglycemic
      individuals is not known. METHODS: People aged > or = 50 years with evidence of
      CV disease and with IFG, IGT, newly detected or established diabetes (on 0 or 1
      oral agent), and a local glycated hemoglobin < 150% of the upper limit of normal
      for that assay were recruited and allocated to (a) either 1 daily injection of
      insulin glargine with the dose titrated to achieve a fasting plasma glucose < or
      = 5.3 mmol/L (95 mg/dL), or standard glycemic care; and (b) either omega-3-acid
      ethyl esters 90 (1 g consisting of EPA 465 mg and DHA 375 mg) or identical
      placebo, according to a 2 x 2 factorial design. The 2 different primary outcomes
      for the insulin and omega-3 fatty acid arms are CV events and CV death,
      respectively. RESULTS: A total of 12,612 (mean age 64, 35% women) people in 40
      countries were randomized during a 2-year period ending December 2005. Eighty-two
      percent had established diabetes, 6% had new diabetes, and 12% had IGT or IFG;
      the mean fasting plasma glucose was 7.3 mmol/L (131 mg/dL). CONCLUSIONS: The
      ORIGIN trial will determine whether or not either or both of these interventions
      can reduce CV events.

PMID- 18082486
TI  - Monitoring the ACTIVE-W trial: some issues in monitoring a noninferiority trial.
AB  - Noninferiority comparisons of new to current therapies and the use of composite
      outcomes represent significant advances in the design of clinical trials. They
      increasingly characterize trials of new cardiovascular agents, posing new
      challenges to Data Safety Monitoring Boards (DSMB) and principal investigators.
      The ACTIVE-W study was a noninferiority comparison of the combination of
      clopidogrel and acetylsalicylic acid versus oral anticoagulant among patients
      with atrial fibrillation. When unexpectedly high rates of stroke and then of the
      composite outcome of stroke, non-central nervous system systemic embolism,
      myocardial infarction, and vascular death emerged, the DSMB modified its
      monitoring plan and conducted its first formal interim analysis much earlier than
      had been planned in the DSMB charter. The study was terminated when only 27% of
      the anticipated outcomes had occurred. This paper discusses issues of appropriate
      stopping guidelines for noninferiority trials and the early emergence of
      significant harm in relation to one component (stroke) of a composite outcome.
      Conditional power was not determined concurrently with the HRs during the
      monitoring of ACTIVE-W; however, the members of the DSMB now believe that such
      calculations should be considered as useful adjuncts to the calculation of HRs
      and could lead to earlier termination of noninferiority trials whose interim
      results suggest futility, without the need for convincing proof of harm.

PMID- 18082487
TI  - Comparing invasive and noninvasive management strategies for acute myocardial
      infarction using administrative databases.
AB  - PURPOSE: The aim of this study was to compare outcomes after acute myocardial
      infarction between regions with low and high catheterization access. METHODS:
      Observational study using administrative databases of patients with acute
      myocardial infarction in provinces with low (Ontario) and high (Quebec and
      British Colombia) access to invasive cardiac procedures (ICP, n = 141718). Using
      instrumental variables to control for confounding, effectiveness of treatment was
      measured on 1-year mortality among marginal patients (patients for whom treatment
      is discretionary and highly dependent on access to ICP). RESULTS: The ICP
      approach was associated with overall decreased mortality (-11%, 95% CI -13% to 
      8%) with statistically significant reductions in low-access regions (-16%, 95% CI
      -21% to -10%). High-access regions (QC -8%, 95% CI -19% to 4%) (BC -2%, 95% CI 
      12% to 7%) exhibited smaller marginal benefits. CONCLUSION: The invasive approach
      benefits all marginal patients, with greater benefits in regions of lower access,
      indicating a threshold of availability above which further mortality benefits are
      negligible.

PMID- 18082489
TI  - Inflammatory responses after intracoronary injection of autologous mononuclear
      bone marrow cells in patients with acute myocardial infarction.
AB  - BACKGROUND: Inflammatory responses after intracoronary injection of autologous
      mononuclear bone marrow cells (mBMC) are not clarified. The aim of this study was
      to investigate the influence of intracoronary injection of mBMC on inflammatory
      mediators in patients with acute myocardial infarction (AMI). METHODS: Patients
      with AMI in the ASTAMI trial (N = 100) treated with percutaneous coronary
      intervention were randomized to intracoronary injections of mBMC or control.
      Fasting blood samples were drawn the day before stem cell transplantation
      (baseline 4-5 days after AMI) and 1 day, 3 days, 2 to 3 weeks, and 3 months after
      transplantation for determination of circulating levels of selected inflammatory
      markers and mRNA levels in whole blood samples. RESULTS: From baseline to day 1,
      the levels of interleukin 6 and the expression of tumor necrosis factor alpha
      mRNA increased significantly in the mBMC group compared to the control group (P <
      .05 for both). The decrease in interleukin 6 levels from baseline to 2 to 3 weeks
      in the mBMC group was less pronounced than in the controls (P < .05), as was also
      the decrease in C-reactive protein levels from baseline to day 1 and day 3 in the
      mBMC group (P < .05). However, from baseline to 3 months the levels of tumor
      necrosis factor alpha and monocyte chemoattractant protein 1 increased less in
      the mBMC group (P < .05 for both). CONCLUSION: Intracoronary injection of mBMC in
      patients with AMI induces a marked short-term inflammatory response, but a
      slightly reduced inflammation after 3 months which may have implications for the
      timing of stem cell transplantation in AMI.

PMID- 18082488
TI  - Myeloid-related protein 8/14 and the risk of cardiovascular death or myocardial
      infarction after an acute coronary syndrome in the Pravastatin or Atorvastatin
      Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction (PROVE IT
      TIMI 22) trial.
AB  - BACKGROUND: Using a transcriptional profiling approach, we recently identified
      myeloid-related protein 8/14 (MRP-8/14) to be expressed by platelets during acute
      myocardial infarction (MI). Elevated concentrations of MRP-8/14 are associated
      with a higher risk for future cardiovascular events in apparently healthy
      individuals but have not been assessed with respect to prognosis in patients with
      acute coronary syndrome. METHODS: We performed a nested case-control study (n =
      237 case-control pairs) among patients enrolled in the Pravastatin or
      Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial
      Infarction 22 (PROVE IT-TIMI 22) trial (mean follow-up 24 months) to investigate
      the risk of cardiovascular death or MI associated with MRP-8/14 measured at 30
      days after an acute coronary syndrome. RESULTS: Patients with cardiovascular
      death or MI after 30 days (cases) had higher median [25th, 75th percentile] MRP
      8/14 levels than patients who remained free of recurrent events (5.6 [2.8, 13.5]
      mg/L vs 4.0 [1.9, 10.1] mg/L, P = .020). The risk of a recurrent cardiovascular
      event increased with each increasing quartile of MRP-8/14 (P-trend = 0.007) such
      that patients with the highest levels had a 2.0-fold increased odds (95% CI 1.1
      3.6, P = .029) of a recurrent event after adjusting for standard risk indicators,
      randomized treatment, and C-reactive protein. Patients with elevated levels of
      MRP-8/14 and high-sensitivity C-reactive protein showed significantly increased
      risk of cardiovascular death or MI compared with patients with the lowest levels
      of both markers (adjusted odds ratio 2.1, 95% CI 1.2-3.8). CONCLUSIONS: Myeloid
      related protein 8/14 may be a useful biomarker of platelet and inflammatory
      disease activity in atherothrombosis and may serve as a novel target for
      therapeutic intervention.

PMID- 18082490
TI  - Biomarker analysis by fluorokine multianalyte profiling distinguishes patients
      requiring intervention from patients with long-term quiescent coronary artery
      disease: a potential approach to identify atherosclerotic disease progression.
AB  - BACKGROUND: The study rationale was to compare the biomarker profile of
      metalloproteinases (MMPs) and inflammation markers (IMs) in patients requiring
      revascularization with that of patients with long-term, clinically quiescent
      coronary artery disease (CAD). METHODS: Seventy-eight patients with symptomatic
      CAD (S-CAD) (7 patients with myocardial infarction and 71 patients with stable
      angina) and 67 patients with asymptomatic CAD (A-CAD) were enrolled. Plasma
      samples were analyzed for MMPs, MMP inhibitors (MMPIs), IMs, coagulation factors,
      and apolipoproteins by use of the fluorokine multianalyte profiling assay.
      RESULTS: Patients with S-CAD had markedly elevated levels of specific MMPs (MMP
      2, MMP-9), MMPIs (alpha2-macroglobulin, tissue inhibitor of MMP 1), IMs (C
      reactive protein; interleukin [IL] 8; IL-10, regulated upon activation, normal T
      cell expressed and secreted [RANTES], endothelin, plasminogen activator inhibitor
      1, and apolipoprotein C-III compared with patients with A-CAD (P < .005 for all
      measurements), whereas patients with A-CAD had significantly greater levels of
      MMP-3 and IL-1alpha compared with patients with S-CAD (P < or = .02 for both
      measurements). CONCLUSIONS: A specific profile of MMPs, IMs, and other biomarkers
      distinguishes the patient with progressive coronary atherosclerosis culminating
      in either elective or emergent percutaneous coronary intervention from the
      patient with quiescent disease. The early implementation of a biomarker analysis
      may identify the patient at risk for plaque progression and refine the definition
      of "stable" angina.

PMID- 18082491
TI  - Kidney dysfunction and fatal cardiovascular disease--an association independent
      of atherosclerotic events: results from the Health, Aging, and Body Composition
      (Health ABC) study.
AB  - BACKGROUND: Impaired kidney function has been associated with increased risk for
      death, myocardial infarction, stroke, and heart failure in high-risk populations.
      We evaluated whether impaired kidney function predicted risk of fatal
      cardiovascular disease independent of prevalent and incident cardiovascular
      events. METHODS: The Health, Aging, and Body Composition study is a cohort of
      well-functioning, elderly participants aged 70 to 79 years at entry. We measured
      serum cystatin C and creatinine from baseline plasma samples of 3044 participants
      and followed them over 6 years, examining the associations among kidney function,
      cardiovascular death, and incident cardiovascular events. Cystatin C was
      categorized as low (< 0.84 mg/L), medium (0.84-1.18 mg/L), or high (> or = 1.19
      mg/L); serum creatinine (cutoff value of > or = 1.3 in women and > or = 1.5 in
      men) and estimated glomerular filtration rate (eGFR; greater and less than 60
      mL/min per 1.73 m2) were dichotomized. RESULTS: During follow-up, 242
      cardiovascular deaths occurred, of which 69 were in participants without prior
      cardiovascular events; 294 incident cardiovascular events occurred including 135
      myocardial infarctions and 163 strokes. Higher cystatin C concentrations were
      significantly associated with cardiovascular death (adjusted hazard ratio [HR]
      1.70, 95% confidence interval [CI] 1.05-2.76 for the medium cystatin C group; and
      HR 2.24, 95% CI 1.30-3.86 for the high cystatin C group, relative to the low
      cystatin C group). The point estimate was of greater magnitude in the analysis
      that excluded prevalent cardiovascular disease (adjusted HR 2.68, 95% CI 0.94
      7.70 for the medium cystatin C group; and HR 4.91, 95% CI, 1.55-15.54 for the
      high cystatin C group). Elevated creatinine levels (adjusted HR 1.54, 95% CI 1.02
      2.33, and HR 2.28, 95% CI 1.10-4.73 among participants without a history of
      cardiovascular disease) were also associated with cardiovascular death. No
      significant association was found between low eGFR and cardiovascular death. In
      addition, cystatin C, low eGFR, or elevated creatinine levels were not associated
      with other cardiovascular events. CONCLUSION: Impaired kidney function is a
      strong predictor of cardiovascular death, particularly among participants without
      prior history of cardiovascular disease.

PMID- 18082492
TI  - Recovery of normal ventricular function in patients with dilated cardiomyopathy:
      predictors of an increasingly prevalent clinical event.
AB  - BACKGROUND: This investigation was designed to identify clinical variables
      associated with recovery of normal ventricular function in patients with dilated
      cardiomyopathy treated with medical therapy. Recovery of normal ventricular
      function with medical treatment of patients with dilated cardiomyopathy is
      observed with increasing frequency. However, the clinical variables associated
      with such dramatic improvement of ventricular performance are poorly defined.
      METHODS: Fifty-three patients with dilated cardiomyopathy and reduced ejection
      fractions who achieved an increase in ejection fraction to > or = 40% with
      medical therapy were identified during follow-up in a dedicated heart failure
      clinic. A cohort of patients frequency-matched on baseline ejection fraction who
      did not recover ventricular systolic function to this magnitude constituted the
      control group. Clinical variables characterizing the 2 groups were compared by
      univariable analysis. Variables that significantly differed between the 2 groups
      were entered in a stepwise logistic regression analysis to identify factors
      independently associated with recovery of ejection fraction to > or = 40%.
      RESULTS: In the final logistic regression model, QRS duration, sex, etiology of
      cardiomyopathy, diabetes, and systolic blood pressure were significantly
      associated with improvement of ejection fraction to > or = 40%. CONCLUSIONS: Five
      clinical variables that are independently associated with improvement of left
      ventricular ejection fraction to normal or near-normal values with medical
      therapy alone were identified by this modeling process. These variables may be
      used to discriminate between patients in whom ventricular function will normalize
      with medical therapy alone and those who will require more aggressive
      pharmacologic or device therapy.

PMID- 18082493
TI  - Pentraxin 3, a new marker for vascular inflammation, predicts adverse clinical
      outcomes in patients with heart failure.
AB  - BACKGROUND: Pentraxin 3 (PTX3) is a novel inflammatory marker produced by
      endothelial cells, smooth muscle cells, and macrophages. The purpose of the
      present study was to examine the clinical significance of plasma PTX3 levels in
      patients with heart failure. METHODS: We measured the plasma PTX3 levels in 196
      patients with heart failure and 60 control subjects without heart failure by
      sandwich enzyme-linked immunosorbent assay. Patients were prospectively followed
      during a median follow-up period of 655 days with the end points of cardiac death
      or progressive heart failure requiring rehospitalization. RESULTS: Plasma PTX3
      concentrations were higher in patients with heart failure than in control
      subjects (P < .0001) and increased as the severity of New York Heart Association
      functional class advanced (P < .0001). A total of 63 cardiac events occurred
      during a follow-up period, and cardiac event-free rate was markedly lower in
      patients with high PTX3 levels than in those with normal PTX3 levels (44.7% vs
      89.2%, P < .0001). The multivariate Cox proportional hazard analysis demonstrated
      that the plasma PTX3 level, but not the high-sensitive C-reactive protein, was
      the independent predictor of cardiac events (hazard ratio 1.20, 95% CI 1.03-1.40,
      P = .0162). Patients were divided into 4 groups based on plasma PTX3 values from
      first to fourth quartile. The highest fourth quartile of plasma PTX3 levels was
      associated with the highest risk of cardiac events (9.23-fold compared with the
      first quartile). CONCLUSIONS: The plasma PTX3 level provides important prognostic
      information for the risk stratification of patients with heart failure.

PMID- 18082494
TI  - Cystatin C and risk of heart failure in the Physicians' Health Study (PHS).
AB  - BACKGROUND: Chronic kidney disease is a risk factor for heart failure (HF).
      Although cystatin C can detect early kidney dysfunction, limited data are
      available on the association between cystatin C and HF. METHODS: In a prospective
      nested case-control study design, we examined whether cystatin C is associated
      with an increased risk of HF in the PHS and whether such an association is
      stronger in hypertensive subjects. We selected 220 cases of incident HF and 220
      controls, matched on age, year of birth, and time of blood collection. Plasma
      cystatin C was measured using an immunonephelometry method. We used conditional
      logistic regression to estimate relative risks (RRs). RESULTS: Compared with the
      lowest tertile, the multivariable adjusted RR (95% CI) for HF was 1.15 (0.69
      1.89) and 1.78 (1.01-3.13) for the second and third tertiles of cystatin C,
      respectively. Additional adjustment for systolic blood pressure and history of
      hypertension attenuated this association (RR = 1.0, 1.23 [0.73-2.09], and 1.61
      [0.90-2.88] from the lowest to the highest tertile, respectively). Furthermore,
      we observed a 4-fold increased risk of HF in the second and third tertiles of
      cystatin C among hypertensive individuals and no meaningful effects of cystatin C
      on HF among nonhypertensive subjects. CONCLUSIONS: Our data demonstrated that
      higher levels of cystatin C are associated with an increased risk of HF and that
      such association may be limited to hypertensive individuals. Additional studies
      are warranted to further examine the relationship between hypertension and
      cystatin C on the risk of HF.

PMID- 18082495
TI  - Amiodarone use after acute myocardial infarction complicated by heart failure
      and/or left ventricular dysfunction may be associated with excess mortality.
AB  - BACKGROUND: We sought to assess the association of amiodarone use with mortality
      during consecutive periods in patients with post-acute myocardial infarction with
      left ventricular systolic dysfunction and/or HF treated with a contemporary
      medical regimen. METHODS: This study used data from VALIANT, a randomized
      comparison of valsartan, captopril, or both in patients with acute myocardial
      infarction with HF and/or left ventricular systolic dysfunction. We compared
      baseline characteristics of 825 patients treated with amiodarone at randomization
      with 13,875 patients not treated with amiodarone. Using Cox models, we examined
      the association of amiodarone use with subsequent mortality during consecutive
      periods after randomization (days 1-16, 17-45, 46-198, and 199-1096). RESULTS:
      Patients treated with amiodarone were older, had higher Killip class, and were
      more likely to have a history of diabetes mellitus and hypertension. Adjusting
      for baseline predictors of mortality, we found that amiodarone use was associated
      with a significant increase in mortality during 3 of the 4 periods: hazard ratio
      1.5, 95% CI (1.1-2.0), P = .02, for days 1 to 16; 2.1 (1.5-2.9), P < .001, for
      days 17 to 45; 1.1 (0.83-1.46), P = .51, for days 46 to 198; and 1.4 (1.2-1.6), P
      < .001, for days 199 to 1096. CONCLUSION: In this study, amiodarone use was
      associated with excess early and late all-cause and cardiovascular mortality.
      These observational findings are in contrast to earlier randomized trials of
      amiodarone and need to be validated prospectively.

PMID- 18082496
TI  - Effects of clopidogrel and aspirin in combination versus aspirin alone on
      platelet activation and major receptor expression in diabetic patients: the
      PLavix Use for Treatment Of Diabetes (PLUTO-Diabetes) trial.
AB  - BACKGROUND: Clopidogrel is widely used in diabetic patients after vascular
      events; however, the ability of this thienopyridine to yield additional
      antiplatelet protection on top of aspirin has never been explored in a controlled
      study with comprehensive assessment of platelet activity. The objective of this
      study was to compare the antiplatelet profiles of clopidogrel + aspirin in
      combination (C + ASA) versus aspirin alone (ASA) in patients with type 2 diabetes
      mellitus. METHODS: Seventy patients with documented diabetes already treated with
      antecedent aspirin were randomly assigned to receive C + ASA or ASA in the PLUTO
      Diabetes trial. Platelet studies included adenosine diphosphate-, collagen-, and
      arachidonic acid-induced aggregometry; PFA-100 (Dade-Behring, Miami, FL) and
      Ultegra (Accumetrics, San Diego, CA) analyzers; and expression of 6 major
      receptors by flow cytometry at baseline and at day 30 after randomization.
      RESULTS: There were no differences in the baseline clinical and platelet
      characteristics between the C + ASA and ASA groups, or subsequent significant
      changes in platelet biomarkers in the ASA group, except for diminished collagen
      induced aggregation (P = .02). In contrast, when compared with the ASA group,
      therapy with C + ASA resulted in significant inhibition of platelet activity
      assessed by adenosine diphosphate aggregation (P = .0001); closure time
      prolongation (P = .0003) and reduction of platelet activation units with Ultegra
      (P = .0001); and expression of platelet/endothelial cell adhesion molecule 1 (P =
      .002), glycoprotein IIb/IIIa antigen (P = .0002), and activity (P = .0001).
      CONCLUSION: Treatment with C + ASA for 1 month provides significantly greater
      inhibition of platelet activity than ASA alone in diabetic patients in this small
      randomized trial. However, despite dual antiplatelet regimen, diabetic patients
      exhibit high residual activity of some platelet biomarkers, including unaffected
      protease-activated receptor 1 receptor expression.

PMID- 18082497
TI  - Right atrial pacing and the risk of postimplant atrial fibrillation in cardiac
      resynchronization therapy recipients.
AB  - BACKGROUND: In patients with cardiac resynchronization therapy (CRT) devices,
      right atrial (RA) pacing introduces a significant prolongation in interatrial
      conduction time, delaying left atrial mechanical systole and curtailing left
      ventricular filling. The resultant increase in left-sided filling pressures may
      facilitate atrial fibrillation (AF). We sought to determine whether the extent of
      RA pacing influences the incidence of AF after CRT. METHODS: Consecutive CRT
      patients (n = 309) followed at our institution were retrospectively studied for
      percentage of RA pacing and incidence of high atrial rates, as determined by
      regular device interrogations. Additional clinical data were collected from the
      medical record. RESULTS: The mean follow-up was 18.1 +/- 13.3 months, during
      which 209 (67.6%) patients had at least 1 detected high atrial rate episode
      consistent with AF. Higher percentages of RA pacing were associated with a
      greater risk of postimplant AF, with its incidence increasing incrementally with
      quartiles of RA pacing: 44.6%, 64.3%, 79.7%, and 81.6%, respectively (P < .001).
      After controlling for all factors predictive of postimplant AF on univariate
      analysis (right atrial pacing quartile, follow-up duration, mitral regurgitation
      severity, and prior AF history), RA pacing quartile remained a significant
      predictor of post-CRT AF (hazard ratio 1.92, 95% CI 1.40-2.62, P < .001) upon
      multivariate analysis. In addition to predicting AF incidence, higher RA pacing
      quartiles were also associated with significantly greater AF burden. CONCLUSIONS:
      Compared to atrial sensing, atrial pacing is associated with a 2-fold increased
      risk of post-CRT AF. Prospective comparison of DDD and VDD pacing modes in CRT is
      warranted.

PMID- 18082498
TI  - A randomized comparison of amiodarone and class IC antiarrhythmic drugs to treat
      atrial fibrillation in patients paced for sinus node disease: the Prevention
      Investigation and Treatment: A Group for Observation and Research on Atrial
      arrhythmias (PITAGORA) trial.
AB  - BACKGROUND: Rhythm control is an important goal in the treatment of recurrent
      atrial tachyarrhythmias (AT). The PITAGORA study was a randomized trial in
      patients paced for sinus node disease (SND), designed to test the noninferiority
      of class IC antiarrhythmic drugs (AADs) to amiodarone in terms of a primary end
      point composed of death, permanent AT, cardiovascular hospitalization, atrial
      cardioversion, or AAD change. METHODS: Randomization was stratified to assign 2
      patients to amiodarone and 2 patients to class IC AADs: propafenone or
      flecainide. One hundred seventy-six patients (46% men, 72 +/- 8 years) were
      enrolled. Device diagnostics continuously monitored AT recurrences and duration.
      RESULTS: In a mean follow-up of 20 +/- 9 months, the primary end point occurred
      in 23 (30.7%) of 75 class IC patients and in 28 (40.0%) of 70 amiodarone
      patients. The absolute difference in the end point incidence (-9.3%; 95% CI
      between 3.7% and -22.3%) confirmed the noninferiority of class IC to amiodarone
      (P = .007). Kaplan-Meier 1-year freedom from AT episodes >10 minutes, 1 day, and
      7 days was 40%, 73%, and 91% for amiodarone and 28%, 78%, and 86% for class IC
      AADs (P = nonsignificant). CONCLUSIONS: In patients paced for SND and suffering
      from AT, class IC AADs proved not to be inferior to amiodarone in terms of the
      primary composite end point described or end points which were differently
      composed of mortality, efficacy, or AAD side effects. The AADs studied also
      showed similar results in terms of symptoms, quality of life, and freedom from AT
      recurrences.

PMID- 18082499
TI  - Comparison of vascular response to zotarolimus-eluting stent versus sirolimus
      eluting stent: intravascular ultrasound results from ENDEAVOR III.
AB  - BACKGROUND: The purpose of this study was to investigate the vascular response of
      zotarolimus-eluting stent (ZES) and sirolimus-eluting stent (SES) using serial
      intravascular ultrasound (IVUS). METHODS: Data were obtained from the Endeavor
      Drug-Eluting Coronary Stent System Versus the Center Siromlimus-Eluting Coronary
      Stent System in De Novo Native Coronary Artery Lesions (ENDEAVOR) III trial, a
      randomized study comparing ZES and SES for the treatment of de novo native
      coronary artery lesions. Serial (baseline and 8-month follow-up) IVUS was
      available in 258 patients (190 ZES, 68 SES). RESULTS: At 8 months, ZES had
      greater percentage of neointimal volume index (ZES 1.1 +/- 0.8 mm3/mm vs SES 0.2
      +/- 0.1 mm3/mm, P < .01), resulting in smaller lumen volume index (6.0 +/- 2.0
      mm3/mm vs 7.0 +/- 2.1 mm3/mm, P < .05). Zotarolimus-eluting stents showed larger
      IVUS-detectable neointimal coverage over stent surface (50.2% vs 10.5%, P < .01)
      and greater mean neointimal thickness (0.19 +/- 0.07 mm vs 0.10 +/- 0.06 mm, P <
      .01). Zotarolimus-eluting stents had a significantly lower incidence of late
      acquired incomplete stent apposition. CONCLUSIONS: Zotarolimus-eluting stent is
      associated with a significantly greater amount of neointimal hyperplasia compared
      with SES. This amount of hyperplasia in ZES is distributed throughout the stent
      at 8-month follow-up.

PMID- 18082500
TI  - A randomized, double-blind, placebo-controlled study of the safety and efficacy
      of intravenous MCC-135 as an adjunct to primary percutaneous coronary
      intervention in patients with acute myocardial infarction: Evaluation of MCC-135
      for left ventricular salvage in acute myocardial infarction (EVOLVE).
AB  - OBJECTIVES: The objective of the study was to test the hypothesis that
      intracellular calcium modulation by 5-methyl-2-[piperazin-1-yl] benzene sulfonic
      acid monohydrate (MCC-135 [Caldaret]; Mitsubishi Pharma Corporation, Osaka,
      Japan) would preserve left ventricular function and reduce infarct size in
      patients undergoing primary percutaneous coronary intervention (PCI) for ST
      elevation myocardial infarction (STEMI). BACKGROUND: Calcium overload inside
      myocytes during ischemia and reperfusion not only affects myocardial function but
      also may be related to myocyte necrosis. MCC-135 is the first in a new class of
      agents that modulate intracellular calcium overload. METHODS: Patients with acute
      STEMI undergoing primary PCI were randomized into placebo, low-dose, and high
      dose MCC-135 groups. The predefined target population was those with anterior
      myocardial infarction and pre-PCI TIMI grade flow 0 or 1. Left ventricular
      ejection fraction (LVEF) on Day 5 was the primary end point. Secondary end points
      included infarct size measured by single photon emission computed tomography and
      by serum cardiac markers. Patients were followed up to 30 days for clinical
      outcome. RESULTS: Among 500 patients enrolled, 141 qualified as the target
      population. In this target population, there was no difference in the LVEF
      between 3 groups (placebo: 47.0% +/- 1.7% [mean +/- SEM], the low dose: 47.4% +/-
      1.7%, the high dose: 45.1% +/- 2.0%). The infarct size on day 5 was not
      significantly different between the groups. The composite clinical outcome
      occurred in 25.5% in the placebo group, in 19.2% in the low-dose group, and in
      34.2% in the high-dose group during a 30-day follow-up period (P =
      nonsignificant). MCC-135 appeared to be safe and well tolerated. CONCLUSION:
      There were no significant benefits of MCC-135 on preservation of LVEF and
      reduction of infarct size on day 5 in patients with STEMI undergoing primary PCI.

PMID- 18082501
TI  - Risk-adjusted sequential probability ratio test control chart methods for
      monitoring operator and institutional mortality rates in interventional
      cardiology.
AB  - BACKGROUND: The objective of this study was to evaluate risk-adjusted sequential
      probability ratio test control charts for the detection of significant
      discrepancies between institution or individual interventional cardiologist
      postprocedural mortality rates and national or local event rate expectations.
      METHODS: Eight thousand nine hundred forty-two percutaneous coronary
      interventional procedures were performed by 27 operators between January 1, 2002,
      and November 30, 2006. The institution-based evaluation included all procedures,
      and the individual-based evaluations included 8750 procedures performed by 18
      operators who had each done at least 100 PCI procedures. Risk-adjusted sequential
      probability ratio test control charts were developed to assess whether the odds
      ratios (ORs) for death were >2.0 for alpha = beta = 0.10. The American College of
      Cardiology 1.1 prediction model was used to risk-adjust both the institution and
      individuals, and an additional local model was used for individuals. RESULTS:
      After national risk adjustment, the local institution did not show mortality of
      more than a 1.5 OR. Two operators had a >2.0 mortality OR after national risk
      adjustment, and one of those remained elevated after local risk adjustment. Of 18
      operators, 10 had insufficient data to allow us to accept or reject the
      hypothesis of increased risk. CONCLUSIONS: The local institution performed within
      national expectations, but 1 operator was identified as having poor performance,
      which prompted an in-depth review of that operator's cases. The review revealed
      that the operator had an unusually high number of patients who presented with
      risk factors not included in the risk-adjustment models. This study highlights
      the utility of risk-adjusted sequential probability ratio test as a method for
      outcomes monitoring and quality control in interventional cardiology.

PMID- 18082502
TI  - Guideline adjudicated fibrinolytic failure: incidence, findings, and management
      in a contemporary clinical trial.
AB  - BACKGROUND: Rescue percutaneous coronary intervention (PCI) is efficacious after
      clinical failure of fibrinolytic therapy and is recommended for those with
      persistent ischemia, hemodynamic, or electrical instability. We sought to
      describe the frequency of fibrinolytic failure (rescue eligibility) as well as
      the patient characteristics associated with rescue eligibility, rescue referral,
      and PCI. METHODS AND RESULTS: Eligibility, indication, and referral for guideline
      based rescue PCI were adjudicated in 221 patients enrolled in the WEST trial.
      WEST treated patients at earliest medical contact and used a
      tenectaplase/enoxaparin regimen. Ninety patients (41%) were adjudicated with
      acute myocardial infarction as rescue eligible of whom 68 were referred for
      rescue PCI. Baseline characteristics did not predict rescue eligibility or
      referral. Emergency angiography before PCI performed a median of 82 minutes
      (interquartile range 50-99) after rescue referral showed TIMI flow grade 2 or 3
      in 34 (50%). Percutaneous coronary intervention was adjudicated as successful in
      58 of 60 attempts. Procedures began approximately 45 minutes sooner in patients
      initially admitted to PCI-capable hospitals. Compared to those with clinically
      successful fibrinolytic therapy, rescue eligible patients demonstrated higher
      median peak creatine phosphokinase (1889 [1243-3746] vs 999 [440-2048], P < .01)
      and 30-day median NT-proBNP levels (748 [391-1916] vs 431 [153-1016], P < .01).
      CONCLUSIONS: Rescue eligibility determined by guideline criteria is common after
      contemporary fibrinolysis and is not predicted by conventional baseline
      characteristics. Half of rescue-referred patients are patent at angiography:
      although contemporary PCI success rates are high, rescue eligibility is
      associated with larger infarctions.

PMID- 18082503
TI  - Use of endothelial progenitor cell capture stent (Genous Bio-Engineered R Stent)
      during primary percutaneous coronary intervention in acute myocardial infarction:
      intermediate- to long-term clinical follow-up.
AB  - AIMS: We assessed the use of the endothelial progenitor cell (EPC) capture stent
      in primary percutaneous intervention in ST-elevation myocardial infarction
      (STEMI). METHODS AND RESULTS: One hundred and twenty patients with acute STEMI
      without cardiogenic shock received 129 EPC capture stents. Procedural success was
      achieved in 95% of patients. Dual antiplatelet therapy was given for a month and
      statin therapy started immediately after the procedure. The study end points are
      major adverse cardiac events inhospital and at 30 days, 6 months, and 1 year.
      Hypertension was present in 47.5% and diabetes mellitus in 30% of the patients.
      The left anterior descending artery was the treated artery in 54% of the
      patients. Mean lesion length was 17.4 +/- 7.15 mm with mean reference vessel
      diameter of 3.18 +/- 0.6 mm. Platelet glycoprotein IIb/IIIa inhibitor was used in
      14% of patients and 58% had thrombosuction before stent implantation. Ninety-five
      percent of patients achieved Thrombolysis in Myocardial Infarction 3 flow with
      cumulative major adverse cardiac event rate at 1.6% inhospital, 4.2% at 30 days,
      5.8% at 6 months, and 9.2% at 1 year. There was 1 patient each with acute and
      subacute stent thrombosis but no incidence of late stent thrombosis. CONCLUSION:
      Using EPC capture stent during primary percutaneous coronary intervention for
      STEMI is feasible and safe.

PMID- 18082504
TI  - Effects of pretreatment with clopidogrel on nonemergent percutaneous coronary
      intervention after fibrinolytic administration for ST-segment elevation
      myocardial infarction: a Clopidogrel as Adjunctive Reperfusion Therapy
      Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 study.
AB  - BACKGROUND: The use of routine nonemergent percutaneous coronary intervention
      (PCI) among patients with ST-segment elevation myocardial infarction (STEMI)
      after fibrinolytic therapy is unknown. We sought to evaluate the effect of
      nonemergent PCI on mortality among patients with STEMI treated with fibrinolytic
      administration and the consequence of clopidogrel pretreatment on this effect.
      METHODS: CLARITY-TIMI 28 randomized 3491 patients with STEMI treated with
      fibrinolytic administration and aspirin to clopidogrel or placebo. All patients
      were to undergo angiography 48 to 192 hours after randomization. Percutaneous
      coronary intervention was performed at the discretion of the treating physician.
      Nonemergent PCI, which was defined as PCI that was not precipitated by recurrent
      myocardial infarction, was performed in 1781 patients (55.7%). RESULTS:
      Nonemergent PCI did not affect 30-day mortality (2.0% vs 2.3% among patients who
      did not undergo PCI). However, nonemergent PCI was associated with lower
      mortality among patients randomized to clopidogrel (1.3% vs 2.8%, P = .04) but
      not among those randomized to placebo (2.6% vs 1.7%, P = .25; interaction P =
      .025). In multivariate modeling, PCI remained associated with lower mortality
      among patients randomized to clopidogrel (OR 0.34, 95% CI 0.13-0.92, P = .034)
      but not placebo (OR 1.41, 95% CI 0.63-3.19, P = .40, interaction P = .028).
      CONCLUSION: Among patients with STEMI treated with fibrinolytic administration
      and aspirin, nonemergent PCI was associated with lower mortality among patients
      pretreated with clopidogrel. These results suggest that routine nonemergent PCI
      is beneficial among such patients, although further confirmatory randomized
      studies are needed.

PMID- 18082505
TI  - Culprit-only or multivessel revascularization in patients with acute coronary
      syndromes: an American College of Cardiology National Cardiovascular Database
      Registry report.
AB  - BACKGROUND: Multivessel (MV) coronary artery disease (CAD) frequently exists in
      patients presenting with non-ST-elevation (NSTE) acute coronary syndromes (ACSs).
      Although an early invasive strategy improves outcome in these patients, there are
      limited data on culprit-only, single-vessel (SV) percutaneous coronary
      intervention (PCI) or MV PCI in the NSTE ACS setting. METHODS: To identify the
      predictors of SV versus MV PCI in patients with ACS and compare their outcomes up
      to hospital discharge, we analyzed the records of 105,866 patients undergoing PCI
      with ACS and MV CAD from 402 centers reported to the American College of
      Cardiology National Cardiovascular Database Registry between 2000 and 2004.
      Demographic, clinical, and angiographic characteristics of the patients were used
      to create a propensity score for SV versus MV PCI. RESULTS: Single-vessel PCI was
      performed in 68% (72,048 patients), whereas the remaining 32% (33,818 patients)
      had MV PCI. Factors independently associated with the performance of SV versus MV
      PCI were presentation with NSTE infarction (vs unstable angina), adjusted odds
      ratio (OR) of 1.29 (95% CI 1.24-1.34); being older, adjusted OR of 1.09 (95% CI
      1.08-1.11) per decade; and presence of total occlusion, adjusted OR of 1.25 (95%
      CI 1.16-1.36). The c-statistic for the model was 0.70. Procedural success was
      achieved in 91% of SV PCI and 88% of MV PCI (P < .001). Inhospital mortality was
      1.3% and 1.2%, respectively (P = .09; adjusted OR 1.11 [95% CI 0.97-1.27], P =
      .13). Rates of morbidity, such as bleeding, development of renal failure, or
      nonfatal cardiogenic shock, were similar for both groups. CONCLUSIONS: In
      patients with MV CAD, presenting with ACS and selected for PCI, performance of MV
      PCI appears to be associated with at least as successful an inhospital outcome as
      SV PCI.

PMID- 18082506
TI  - Role of magnetic resonance imaging in arrhythmogenic right ventricular dysplasia:
      insights from the North American arrhythmogenic right ventricular dysplasia
      (ARVD/C) study.
AB  - BACKGROUND: Prior reports describing magnetic resonance (MR) imaging
      abnormalities in arrhythmogenic right ventricular dysplasia (ARVD/C) were limited
      by nonuniform inclusion criteria. The aim of our study was to define the
      prevalence, sensitivity, and specificity of quantitative MR imaging findings in
      the probands of multidisciplinary study of right ventricular dysplasia. METHODS:
      Individuals with ventricular arrhythmias of left bundle-branch block morphology
      meeting the Task Force criteria for ARVD/C underwent MR imaging. The MR images
      were compared with 10 patients with idiopathic ventricular tachycardia (VT) and
      25 controls. Of the 42 study probands, 40 met the Task Force criteria exclusive
      of MR imaging findings. All MR images were interpreted in a blinded fashion.
      RESULTS: Right ventricle fat infiltration was reported in 24 (60%) probands and
      none of the patients with idiopathic VT or controls. Six patients (15%) had fat
      infiltration of the left ventricle. Right ventricle regional dysfunction was
      observed in 32 probands (80%) and none of the patients with idiopathic VT or
      controls. Qualitative RV function was abnormal in 26 probands (60%); however,
      quantitative RV ejection fraction was abnormal in 85% (24/28) of the probands. An
      RV ejection fraction <50% had a sensitivity of 73% and a specificity of 95% in
      diagnosis of ARVD/C. CONCLUSIONS: Fat infiltration is seldom the only MR imaging
      abnormality and is less sensitive for ARVD/C diagnosis compared with RV regional
      dysfunction. Qualitative estimates of RV function may underestimate the
      prevalence of RV dysfunction in ARVD/C. Quantitative evaluation of RV by MR
      imaging may have a high sensitivity and specificity for ARVD/C diagnosis.

PMID- 18082507
TI  - Predictive value of coronary calcifications for future cardiac events in
      asymptomatic individuals.
AB  - BACKGROUND: Reliable risk stratification is crucial for efficient prevention of
      coronary artery disease. The following prospective study determined the
      predictive value of coronary calcifications for future cardiovascular events.
      METHODS: We included 1726 asymptomatic individuals (1018 men, 708 women, age 57.7
      +/- 13.3 years) referred for a cardiological examination. Coronary calcifications
      were determined with the Imatron C 150 XP electron beam computed tomography
      scanner. For quantification of coronary calcifications, we calculated the
      Agatston score. Over a mean observation period of 40.3 +/- 7.3 months we
      registered the event rate for cardiac death (CD) and myocardial infarction (MI).
      RESULTS: The Agatston score in patients who died of CD (n = 65) or had an MI (n =
      114) was significantly higher compared with those without cardiac events (458 +/-
      228 vs 206 +/- 201, P < .01). An Agatston score above the 75th percentile was
      associated with a significantly higher annualized event rate for MI (3.6% vs
      1.6%, P < .05) and for CD (2.2% vs 0.9%) compared with patients with scores below
      the 75th percentile. No cardiac events were observed in patients where coronary
      calcifications could be excluded. CONCLUSIONS: By determination of coronary
      calcifications, patients at risk for future MI and CD could be identified within
      an asymptomatic population independent of concomitant risk factors. At the same
      time, future cardiovascular events could be excluded in patients without coronary
      calcifications.

PMID- 18082508
TI  - Failure of digital echocardiography to accurately diagnose intracardiac shunts.
AB  - BACKGROUND: Intravenous agitated saline injection during transthoracic
      echocardiography assists in the detection of right to left intracardiac and
      intrapulmonary shunts. Whether digital echocardiography offers comparable
      sensitivity and specificity to analog tape recording to assess shunts is unknown.
      Technical differences between methods could lead to significant differences in
      shunt detection. METHODS: Agitated saline was injected intravenously at rest and
      with Valsalva in 189 consecutive patient studies (406 injections).
      Echocardiographers assessed presence and degree of left ventricle contrast on
      simultaneously recorded analog tape and digital echocardiography images in
      blinded fashion. RESULTS: Digital echocardiography had low overall sensitivity
      (rest 0.50, valsalva 0.63, late 0.39) compared to analog tape. Longer clip
      lengths improved sensitivity for detection of late contrast passage (rest 0.50,
      valsalva 0.67, late 0.46). CONCLUSION: Digital echocardiography saline contrast
      studies have poor sensitivity for assessment of intracardiac shunts versus analog
      tape, and increasing clip length only modestly increases sensitivity. Joint
      Photographic Experts Group digital compression losses may be an important cause
      of failure to detect intracardiac shunts, including patent foramen ovale.

PMID- 18082509
TI  - Pulmonary vascular input impedance is a combined measure of pulmonary vascular
      resistance and stiffness and predicts clinical outcomes better than pulmonary
      vascular resistance alone in pediatric patients with pulmonary hypertension.
AB  - BACKGROUND: Pulmonary vascular resistance (PVR) is the current standard for
      evaluating reactivity in children with pulmonary arterial hypertension (PAH).
      However, PVR measures only the mean component of right ventricular afterload and
      neglects pulsatile effects. We recently developed and validated a method to
      measure pulmonary vascular input impedance, which revealed excellent correlation
      between the zero harmonic impedance value and PVR and suggested a correlation
      between higher-harmonic impedance values and pulmonary vascular stiffness. Here
      we show that input impedance can be measured routinely and easily in the
      catheterization laboratory, that impedance provides PVR and pulmonary vascular
      stiffness from a single measurement, and that impedance is a better predictor of
      disease outcomes compared with PVR. METHODS: Pressure and velocity waveforms
      within the main pulmonary artery were measured during right heart catheterization
      of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH
      undergoing reactivity evaluation (49 subjects, 95 conditions). A correction
      factor needed to transform velocity into flow was obtained by calibrating against
      cardiac output. Input impedance was obtained off-line by dividing Fourier
      transformed pressure and flow waveforms. RESULTS: Exceptional correlation was
      found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x
      + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of
      impedance was found to best correlate with indexed pulse pressure over stroke
      volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n
      = 25), cumulative logistic regression between outcomes to total indexed impedance
      was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 =
      0.3131). CONCLUSIONS: Input impedance can be consistently and easily obtained
      from pulse-wave Doppler and a single catheter pressure measurement, provides
      comprehensive characterization of the main components of RV afterload, and better
      predicts patient outcomes compared with PVR alone.

PMID- 18082510
TI  - Interactions of wine drinking with omega-3 fatty acids in patients with coronary
      heart disease: a fish-like effect of moderate wine drinking.
AB  - BACKGROUND: Moderate alcohol drinking and marine omega-3 fatty acids (omega3)
      have both been associated with low mortality from coronary heart disease (CHD).
      However, there is little data evaluating the interactions of wine ethanol
      drinking with omega3 in CHD patients. METHODS: The relationships between wine
      drinking and marine omega3 were evaluated in a cross-sectional study in patients
      with CHD participating in a randomized trial testing the effect of a high alpha
      linolenic acid (ALA, the main plant omega3) diet. Daily ethanol intake was
      calculated as energy and expressed as a percentage of total energy. Plant and
      marine omega3 in the diet were carefully evaluated in each patient in both
      groups. RESULTS: Patients were classified according to their habitual consumption
      of ethanol. Patients in the "high ALA group" and controls ("low ALA group") were
      analyzed separately. Within each group, there was a progressive increase in
      marine omega3 levels with increased alcohol intake, with a level of
      eicosapentanoic acid (EPA) that increased by 50% (P < .005) and 37% (P < .05) in
      the low and high ALA groups, respectively. After controlling for potential
      confounders (including dietary EPA) in a multivariate linear model, the
      association between wine ethanol and EPA remained significant in the low (P <
      .001) and high (P < .05) ALA groups. CONCLUSION: In these patients with CHD,
      moderate wine drinking was associated with higher marine omega3 concentrations
      than no alcohol use. Although the data have to be confirmed in large groups, this
      effect of wine comparable to that of fish may partly explain the protective
      effects of wine drinking against CHD.

PMID- 18082511
TI  - Effect of pulmonary artery angioplasty on exercise function after repair of
      tetralogy of Fallot.
AB  - BACKGROUND: The slope of the minute ventilation versus CO2 production
      relationship (VE/VCO2 slope) is an index of gas exchange efficiency during
      exercise. In patients with repaired tetralogy of Fallot (rTOF), it correlates
      negatively with exercise capacity and is one of the best predictors of peak
      oxygen consumption (VO2). In these patients, the magnitude of the VE/VCO2 slope
      is related to the severity of pulmonary blood flow maldistribution (PBFM). The
      purpose of this study was to determine whether, in patients with rTOF,
      improvements in PBFM after a successful balloon angioplasty procedure (BAP)
      result in improvements in peak VO2 and gas exchange during exercise. METHODS:
      Seventeen patients with rTOF and residual pulmonary artery stenoses referred for
      BAP were recruited. Exercise tests were performed and PBFM determined before and
      after BAP. RESULTS: Nine patients (group 1) had a successful BAP (ie, improvement
      of >5 percentage points in PBFM); 8 did not (group 2). Patients in group 1 had
      significantly greater improvements in VE/VCO2 slope, peak VO2, and peak oxygen
      pulse (an index of forward stroke volume at peak exercise) than did patients in
      group 2. A significant correlation existed between the improvement in PBFM and
      the decline in the VE/VCO2 slope (r = -0.70, P = .002). Changes in peak oxygen
      pulse accounted for 89% of the improvement in peak VO2. CONCLUSIONS: In these
      patients, a successful BAP resulted in improved peak VO2 and more efficient gas
      exchange during exercise. The improvement in peak VO2 appeared to be mediated by
      an increase in forward stroke volume.

PMID- 18082512
TI  - Increased central aortic stiffness and left ventricular mass in normotensive
      young subjects after successful coarctation repair.
AB  - BACKGROUND: Hypertension occurs in 20% to 40% of survivors of anatomically
      successful repair of aortic coarctation (CoA). The aim of the present study was
      to examine the role of central aortic function in this setting. METHODS: Forty
      normotensive asymptomatic subjects with successful CoA repair (age 12 +/- 8
      years) and 20 age- and sex-matched control subjects underwent detailed magnetic
      resonance imaging investigation of the thoracic aorta and left ventricle. Aortic
      distensibility, compliance, and stiffness beta index were calculated in the
      central (precoarctation) and descending (postcoarctation) aorta. Aortic pulse
      wave velocity was measured and left ventricular mass was calculated. RESULTS:
      Compared to control subjects, CoA subjects had markedly decreased central aortic
      distensibility (2.8 +/- 0.7 vs 4.2 +/- 0.5 mm Hg(-1) x 10(-3), P < .001) and
      compliance (1.7 +/- 0.3 vs 2.5 +/- 0.6 mm2 mm Hg(-1), P < .001) and increased
      stiffness beta index (5.2 +/- 1 vs 2.5 +/- 0.6, P < .001). Pulse wave velocity
      was also significantly increased in the CoA subjects (4.7 +/- 1.3 vs 3.3 +/- 0.6
      m/sec, P < .001). Left ventricular mass index was higher in the CoA subjects (84
      +/-11 vs 73 +/-10 g/m2, P = .01) and correlated significantly with aortic
      stiffness beta index (r2 = 0.8, P < .0001). By contrast, descending aortic
      characteristics were similar in the CoA and control subjects. CONCLUSION: Central
      aortic stiffness is markedly increased and associated with increased left
      ventricular mass in normotensive young subjects after successful early repair of
      CoA.

PMID- 18082513
TI  - Comparison of clinical characteristics and arterial remodeling by intravascular
      ultrasonic imaging in three age groups (< or =55, 56 to 69 and > or =70 years) of
      Japanese patients with acute myocardial infarction.
AB  - Recent epidemiologic, pathologic, and intravascular ultrasound (IVUS) studies
      have shown that there are differences in coronary risk factors or plaque
      morphology between younger and older patients with acute myocardial infarctions
      (AMIs). This study examined clinical background and plaque morphology using IVUS
      in younger and older adults with AMIs in Japan. The study population consisted of
      96 patients with AMIs, for whom preinterventional IVUS images were obtained.
      Patients were classified into 3 groups: a young group (aged < or =55 years), a
      middle-aged group (aged 56 to 69 years), and an old group (aged > or =70 years).
      The remodeling index was defined as the ratio of the external elastic membrane
      area at the culprit lesion to the external elastic membrane area at the proximal
      reference site. Expansive remodeling was defined as a remodeling index >1.05 and
      constrictive remodeling as a remodeling index <0.95. The frequency of
      hypercholesterolemia was significantly different among the 3 age groups. Total
      cholesterol (p <0.001), low-density lipoprotein cholesterol (p <0.005), and
      triglyceride (p <0.05) levels and body mass index (p <0.001) in the young group
      were significantly higher than in the old group. On IVUS images, constrictive
      remodeling was most common in the young group, whereas expansive remodeling
      occurred most commonly in the middle-aged and old groups. In conclusion, this
      study demonstrated that patients with AMIs in the young group had higher levels
      of hypercholesterolemia, obesity, and constrictive remodeling compared with those
      in the old group. The differences in arterial remodeling of the culprit lesions
      between younger and older patients with AMIs may reflect different biologic
      mechanisms of plaque activation and destabilization.

PMID- 18082514
TI  - Prevalence, predictors, time course, and long-term clinical implications of left
      ventricular functional recovery after mechanical reperfusion for acute myocardial
      infarction.
AB  - This study prospectively evaluated the prevalence, predictors, time course, and
      prognostic impact of left ventricular (LV) functional recovery after successful
      primary percutaneous coronary intervention in 228 consecutive patients with acute
      myocardial infarctions (AMIs) and LV dysfunction. Serial echocardiographic exams
      were performed within 24 hours (time 1) and at 1 month (time 2) and 6 months
      (time 3) after AMI. Overall, 133 patients (58%) showed significant LV functional
      recovery (> or =10% ejection fraction increase compared with time 1 or ejection
      fraction > or =50%) at time 3. Early (from time 1 to time 2) and late (from time
      2 to time 3) functional recovery patterns were detected in 102 patients (45%) and
      31 patients (14%), respectively. Independent predictors of LV functional recovery
      were enzymatic infarct size (p = 0.0001), time from symptom onset to reperfusion
      (p = 0.022), extent and severity of baseline LV wall motion abnormalities (p =
      0.007), and female gender (p = 0.031). Six-month LV remodeling rates were 36% and
      64% in patients with and without LV functional recovery (p = 0.0001). The five
      year cardiac death rate was significantly lower in patients with LV functional
      recovery than in those without (8% vs 18%, respectively, p = 0.024). The time
      course of LV functional recovery during 6 months did not significantly affect
      long-term survival. In conclusion, after successful mechanical reperfusion of
      AMIs, nearly half of patients showed poor LV functional recovery. The presence of
      significant LV functional recovery 6 months after reperfused AMI, but not the
      specific time course of recovery, is clearly associated with a better long-term
      clinical outcome. Simple baseline variables can predict the improvement of
      cardiac function after reperfused AMI.

PMID- 18082515
TI  - Effect on outcome of an increase of serum cardiac troponin T in patients with
      healing or healed ST-elevation myocardial infarction.
AB  - Recently, an association between minimally elevated cardiac troponin levels and
      cardiovascular risk in the general population has been reported. However, the
      prevalence and clinical importance of elevated cardiac troponin T (cTnT) levels
      remain unclear in patients with histories of myocardial infarction (MI). In this
      study, 1,807 consecutive patients with ST-segment elevation MIs were
      prospectively studied (77.1% men; mean age 64.4 years). Venous blood samples were
      obtained in the chronic stage of MI (28 +/- 7 days after onset), and serum cTnT
      levels were determined. During the average follow-up of 1,042 days, 84 patients
      died and 83 had nonfatal reinfarctions. Patients with cTnT levels in the highest
      quartile (> or = 0.040 ng/ml [n = 353]) had a higher incidence of all-cause death
      (8.2% vs 5.2%, p = 0.049) and nonfatal reinfarction (8.3% vs 5.1%, p = 0.048)
      than patients with cTnT levels from the lower 3 quartiles (<0.040 ng/ml [n =
      1,064]). Multivariate Cox regression analysis revealed that a minimally elevated
      cTnT level (> or =0.040 ng/ml) was a significant predictor of all-cause mortality
      (hazard ratio 1.79, 95% confidence interval 1.10 to 2.90, p <0.02) and nonfatal
      reinfarction (hazard ratio 1.50, 95% confidence interval 1.13 to 2.20, p <0.03).
      Subgroup analysis showed that an elevated cTnT level was also a predictor of all
      cause mortality and nonfatal reinfarction in patients without heart failure. In
      conclusion, minimally elevated cTnT levels in the chronic stage of MI predicted
      long-term adverse clinical outcomes.

PMID- 18082516
TI  - Patterns and implications of B-type natriuretic peptide measurement in patients
      with non-ST-segment elevation acute coronary syndromes.
AB  - Elevated B-type natriuretic peptide (BNP) levels are associated with increased
      risk for mortality in patients with non-ST-segment-elevation (NSTE) acute
      coronary syndromes (ACS). However, the optimal use of BNP measurement for the
      risk stratification of these patients remains unclear. This study was conducted
      to analyze patterns of, and factors associated with, BNP measurement in patients
      with NSTE ACS from 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? (CRUSADE) quality improvement
      initiative from 2003 through 2006. The association of degree of BNP elevation
      with in-hospital mortality in patients with measured BNP levels across risk
      categories was also analyzed. A total of 16,323 of 77,071 patients (21.2%) from
      486 hospitals had BNP levels measured; the rate of BNP measurement by quarter
      increased from 5.1% to 27.7% during this analysis. Factors most strongly
      associated with BNP measurement included signs of heart failure on presentation,
      older age, previous heart failure, faster presenting heart rate, and higher body
      mass index. The adjusted risk for mortality was higher in patients who had BNP
      levels measured than in those who did not (adjusted odds ratio 1.14, 95%
      confidence interval 1.03 to 1.25). In patients with BNP levels measured, a higher
      degree of BNP elevation was associated with incrementally higher in-hospital
      mortality rates across risk categories. BNP levels were measured in approximately
      1/5 of patients with NSTE ACS in contemporary practice. BNP was most frequently
      measured in patients presenting with high-risk characteristics, but the
      association of incremental increases in BNP levels with higher mortality rates
      was similar across risk categories. In conclusion, more widespread measurement of
      BNP levels for risk stratification of patients with NSTE ACS may be warranted.

PMID- 18082517
TI  - Effect of thrombocytopenia on outcomes following treatment with either enoxaparin
      or unfractionated heparin in patients presenting with acute coronary syndromes.
AB  - Thrombocytopenia is associated with an increased risk for adverse cardiac events
      and bleeding in patients presenting with acute coronary syndromes (ACS) treated
      with unfractionated heparin (UFH). Enoxaparin has been shown to improve outcomes
      in ACS; however, its effect on the development of thrombocytopenia in this
      population is not well documented. This study was conducted to examine the
      incidence and clinical importance of thrombocytopenia in patients presenting with
      non-ST-elevation ACS randomized to treatment with enoxaparin or UFH.
      Thrombocytopenia was defined as a platelet count <100 x 10(9)/L or a >50%
      decrease from baseline. Thrombocytopenia developed in a total of 93 of 3,910
      patients during the follow-up period of 14 days; the incidence was similar
      between study arms. The development of thrombocytopenia was associated with more
      frequent death, nonfatal myocardial infarction, and urgent revascularization
      during the study period (odds ratio 2.96, p = 0.001). This association was
      independent of assignment to treatment with enoxaparin or UFH (p for interaction
      = 0.47). Major bleeding was also more common in patients with thrombocytopenia
      regardless of treatment. In conclusion, thrombocytopenia is a significant
      correlate of adverse events in patients presenting with non-ST-elevation ACS
      treated with either enoxaparin or UFH.

PMID- 18082518
TI  - Relation of baseline plasma phospholipid levels to cardiovascular outcomes at two
      years in men with acute coronary syndrome referred for coronary angiography.
AB  - In addition to cholesterol and triglycerides, plasma also contains phospholipids.
      The choline-containing phospholipids constitute >90% of total plasma
      phospholipids. To date, no studies have looked specifically at the prognostic
      significance of total phospholipids in patients with known or suspected coronary
      artery disease. The present study investigated the long-term prognostic
      significance of total choline-containing phospholipid levels in a well
      characterized cohort of 193 men with acute coronary syndromes who were referred
      for coronary angiography at a Department of Veterans Affairs Medical Center. All
      patients were followed prospectively for the development of vascular outcomes.
      After controlling for a variety of baseline variables (including established
      biomarkers such high-sensitivity C-reactive protein and fibrinogen), plasma
      phospholipid values (analyzed as a continuous variable) were a strong and
      independent predictor of each of the individual end points of all-cause mortality
      (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41 to 0.90, p = 0.0126),
      cardiac mortality (HR 0.49, 95% CI 0.29 to 0.81, p = 0.0057), and myocardial
      infarction (HR 0.71, 95% CI 0.52 to 0.98, p = 0.0342) when using a Cox
      proportional-hazards model. In addition, baseline phospholipid values were also
      an independent predictor of the composite outcome of all-cause mortality, fatal
      or nonfatal myocardial infarction, or stroke (HR 0.66, 95% CI 0.49 to 0.90, p =
      0.0075). In conclusion, these data demonstrate that low baseline levels of total
      choline-containing phospholipid are a strong and independent predictor of
      cardiovascular outcomes (including mortality) in patients with acute coronary
      syndromes.

PMID- 18082519
TI  - Comparison of prognostic value of pharmacologic stress echocardiography in chest
      pain patients with versus without diabetes mellitus and positive exercise
      electrocardiography.
AB  - The aim of this study was to compare the prognostic value of pharmacologic stress
      echocardiography in diabetic and nondiabetic patients with chest pain and
      intermediate- to high-threshold positive exercise electrocardiographic results. A
      total of 935 patients with chest pain (131 diabetic patients) with ST-segment
      depression > or =1 mm on exercise electrocardiography at > or =75-W workload
      underwent dipyridamole (n = 786) or dobutamine (n = 149) stress echocardiography
      and were followed up for the occurence of hard (death and infarction) and major
      events (death, infarction, and late revascularization). During a median follow-up
      of 26 months, 158 events (51 deaths, 28 myocardial infarctions, and 79 late
      revascularizations) occurred: 34 in diabetic and 124 in nondiabetic patients (26%
      vs 15%, p = 0.003). Independent predictors of hard events were age, diabetes, and
      ischemia at stress echocardiography. Five-year hard event rates were 24% in
      patients with and 4% in those without ischemia (p <0.0001). Independent
      predictors of major events were age, diabetes, hypercholesterolemia, smoking
      habit, antianginal therapy at the time of testing, and ischemia at stress
      echocardiography. Five-year major event rates were 46% in patients with and 7% in
      those without ischemia (p <0.0001). Stress echocardiography results yielded
      effective prognostic information in diabetic and nondiabetic patients. However,
      the latter had worse outcomes in both the presence and absence of ischemia.
      Nevertheless, a nonischemic test result predicted an uneventful 6-month period
      and 2% major event rate at 1-year follow-up in both populations. In conclusion,
      stress echocardiography was effective in risk stratifying diabetic and
      nondiabetic patients with intermediate- to high-threshold ischemic exercise
      electrocardiographic results. However, major event rates associated with a
      nonischemic test result were similar in diabetic and nondiabetic patients during
      the first year of follow-up and markedly increased in the former thereafter.

PMID- 18082520
TI  - Comparison of cardiovascular events in patients with angiographically documented
      coronary narrowing with combined renin-angiotensin system inhibitor plus statin
      versus renin-angiotensin system inhibitor alone versus statin alone (from the
      Japanese Coronary Artery Disease Study).
AB  - Statins and renin-angiotensin system (RAS) inhibitors are 2 classes of drugs
      prescribed frequently in clinical practice that may have pleiotropic effects in
      addition to cholesterol-lowering and blood pressure-lowering effects,
      respectively. Combined treatment with statins and RAS inhibitors may have
      additional benefits beyond each monotherapy. We assessed the usefulness of the
      combined treatment in the Japanese Coronary Artery Disease (JCAD) Study
      population. In the JCAD Study, 13,812 patients with angiographically shown
      narrowing in > or =1 of 3 major coronary arteries were followed up for a mean of
      2.7 years. The primary end point of the study was all cardiovascular events. In
      the present study, baseline covariates possibly influencing the event rate were
      adjusted between the control and treatment groups. Although there were no
      statistically significant differences in event rates between patients receiving
      neither statins nor RAS inhibitors and those receiving either drug, Kaplan-Meier
      analysis showed a 22% decrease (p = 0.0286) in the event rate with combined
      treatment. In conclusion, statins combined with RAS inhibitors may decrease
      cardiovascular events in patients with coronary artery disease.

PMID- 18082521
TI  - Usefulness of 64-slice multidetector computed tomography for detecting drug
      eluting in-stent restenosis.
AB  - The aim of this study was to evaluate the accuracy of a new-generation spiral
      multidetector computed tomographic scanner (the Brilliance 64) in the diagnosis
      of coronary in-stent restenosis (ISR). Forty-one patients with 87 coronary stents
      (70 drug-eluting stents) implanted were examined. Patients underwent
      multidetector computed tomography (MDCT) 6.7 +/- 6.9 days before scheduled
      invasive coronary angiography, using intravenous contrast enhancement. Images
      were reconstructed in multiple formats using retrospective electrocardiographic
      gating. Stents were viewed in their long and short axes and were visually
      classified for the presence or absence of binary ISR (diameter reduction >50%),
      including the 5-mm borders proximal and distal to the stent. ISR was found by
      invasive coronary angiography in 13 of the stented segments (15%) and in 8
      patients (19%). Of these, 11 cases of ISR were correctly detected by MDCT;
      additionally, 1 severely calcified stented segment was considered as occluded by
      MDCT (sensitivity 84%, 95% confidence interval [CI] 54% to 98%). Seventy-three of
      74 stented segments without ISR were correctly classified by MDCT (specificity
      97%, 95% CI 93% to 100%), whereas 2 stented segments were classified as false
      negative ISR. The positive predictive value was 92% (95% CI 84% to 97%), the
      negative predictive value was 97% (95% CI 90% to 99%), and predictive accuracy
      was 96% (95% CI 90% to 99%). After the exclusion of the calcified stented
      segment, the sensitivity, specificity, positive predictive value, negative
      predictive value, and predictive accuracy were 84% (95% CI 74% to 91%), 100% (95%
      CI 96% to 100%), 100% (95% CI 96% to 100%), 97% (CI 90% to 99%), and 98% (95% CI
      92% to 99%), respectively. In conclusion, even with improved scanner technology,
      the sensitivity for the detection of ISR was moderate (84%). Thus, further
      studies are needed to determine whether MDCT will be a clinically useful and cost
      effective tool for the evaluation of ISR in the clinical arena.

PMID- 18082523
TI  - Relation of haptoglobin phenotype to early vascular changes in patients with
      diabetes mellitus.
AB  - Haptoglobin (Hp) is an antioxidant protein and the major susceptibility gene for
      atherosclerosis in diabetic patients. The effect of Hp phenotype on arterial
      compliance and metabolic and inflammatory parameters was investigated. Patients
      were divided into 3 groups according to Hp phenotype of Hp 2-2, Hp 2-1, and Hp 1
      1. Arterial elasticity of large and small arteries was evaluated using the pulse
      wave contour analysis method. The large-artery elasticity index (LAEI) was lower
      in patients with Hp 2-2 compared with Hp 1-1 (8.4 +/- 2.3 vs 12.6 +/- 4.1 ml/mm
      Hg x 100; p <0.0001). The difference in LAEIs between the Hp 2-1 and Hp 1-1
      groups was also significant (9.9 +/- 2.6 vs 12.6 +/- 4.1 ml/mm Hg x 100; p =
      0.025). The Hp 2-2 and Hp 2-1 groups did not differ from one another. The small
      artery elasticity index (SAEI) was significantly lower in patients with Hp 2-2
      compared with Hp 1-1 (2.8 +/- 1.0 vs 4.4 +/- 1.9 ml/mm Hg x 100; p = 0.004).
      Differences in SAEIs between patients with Hp 2-1 and Hp 1-1, as well as those
      with Hp 2-1 and Hp 2-2, were not detected. Systemic vascular resistance differed
      significantly across groups, driven by the difference between patients with Hp 2
      2 and Hp 1-1. In conclusion, LAEI and SAEI were significantly lower and systemic
      vascular resistance was higher in homozygotes for the 2 allele (Hp 2-2) compared
      with patients with Hp 2-1 or Hp 1-1 phenotypes. Differences in arterial
      elasticity were detected despite the lack of by-phenotype differences in glycemic
      control, blood pressure, or presence of cardiovascular risk factors.

PMID- 18082522
TI  - Exercise training amount and intensity effects on metabolic syndrome (from
      Studies of a Targeted Risk Reduction Intervention through Defined Exercise).
AB  - Although exercise improves individual risk factors for metabolic syndrome (MS),
      there is little research on the effect of exercise on MS as a whole. The
      objective of this study was to determine how much exercise is recommended to
      decrease the prevalence of MS. Of 334 subjects randomly assigned, 227 finished
      and 171 (80 women, 91 men) had complete data for all 5 Adult Treatment Panel III
      defined MS risk factors and were included in this analysis. Subjects were
      randomly assigned to a 6-month control or 1 of 3 eight-month exercise training
      groups of (1) low amount/moderate intensity (equivalent to walking approximately
      19 km/week), (2) low amount/vigorous intensity (equivalent to jogging
      approximately 19 km/week), or (3) high amount/vigorous intensity (equivalent to
      jogging approximately 32 km/week). The low-amount/moderate-intensity exercise
      prescription improved MS relative to inactive controls (p <0.05). However, the
      same amount of exercise at vigorous intensity was not significantly better than
      inactive controls, suggesting that lower-intensity exercise may be more effective
      in improving MS. The high-amount/vigorous-intensity group improved MS relative to
      controls (p <0.0001), the low-amount/vigorous-intensity group (p = 0.001), and
      the moderate-intensity group (p = 0.07), suggesting an exercise-dose effect. In
      conclusion, a modest amount of moderate-intensity exercise in the absence of
      dietary changes significantly improved MS and thus supported the recommendation
      that adults get 30 minutes of moderate-intensity exercise every day. A higher
      amount of vigorous exercise had greater and more widespread benefits. Finally,
      there was an indication that moderate-intensity may be better than vigorous
      intensity exercise for improving MS.

PMID- 18082524
TI  - Comparison of echocardiographic measures of left ventricular diastolic function
      in early hypertension.
AB  - Left ventricular (LV) diastolic dysfunction identifies patients at risk of
      developing heart failure and may be common in patients with hypertension. The
      prevalence of LV diastolic dysfunction in patients with newly diagnosed
      hypertension was compared using criteria provided by the Canadian Consensus,
      European Study Group, and American Medical Association guidelines. One hundred
      twenty patients with newly diagnosed untreated hypertension (mean age 46.9 +/-
      2.1 years; 62 men, 58 women) with increased blood pressure (clinic >140/90 mm Hg,
      daytime ambulatory >135/85 mm Hg) underwent comprehensive 2-dimensional
      echocardiography. Transmitral inflow velocities were measured using pulse-wave
      Doppler with and without Valsalva's maneuver, and a comprehensive assessment of
      tissue Doppler velocities was performed. The prevalence of LV diastolic
      dysfunction varied according to criteria used. There was a high prevalence of LV
      diastolic dysfunction (59%; n = 71) using Canadian Consensus guidelines; 27% of
      patients (n = 32) had a pseudonormal pattern unmasked using Valsalva's maneuver
      and 32% (n = 39) had impaired relaxation at rest. Significantly fewer patients
      (10%; n = 12) had this diagnosis using European or American Medical Association
      guidelines (23%; n = 27). Using tissue Doppler imaging (early-late diastolic
      velocity ratio <1), the prevalence of LV diastolic dysfunction was 59% (n = 71),
      identical to findings using the Canadian Consensus guidelines. In conclusion,
      current national consensus guidelines defining LV diastolic dysfunction varied
      widely and underdiagnosed LV diastolic dysfunction in patients with newly
      diagnosed hypertension. Tissue Doppler imaging assessment is a rapidly and widely
      available tool that is as sensitive as the most stringent national guidelines and
      should be systematically incorporated into a more comprehensive assessment of LV
      diastolic dysfunction in this population.

PMID- 18082525
TI  - Effects of surgical septal myectomy on left ventricular wall thickness and
      diastolic filling.
AB  - This study was conducted to examine the late effects of surgical myectomy on left
      ventricular (LV) structure and diastolic function in patients with obstructive
      hypertrophic cardiomyopathy. Patients with hypertrophic cardiomyopathy who had
      complete echocardiographic studies before and > or =6 months after myectomy were
      included in this retrospective analysis of cavity dimension, septal and LV
      posterior wall thicknesses, and Doppler flow variables. Compared with
      preoperative measurement, mean septal thickness (23.6 vs 19.5 mm, p <0.001) and
      LV posterior wall thickness (14.2 vs 12.4 mm, p <0.001) were smaller after
      myectomy. Likewise, mitral inflow Doppler velocity curves indicated improvement
      in LV filling, with decreased mitral E velocity (0.95 to 0.87 m/s, p = 0.008). In
      conclusion, the long-term benefits of this operation may be mediated in part by
      favorable LV remodeling and changes in LV diastolic filling.

PMID- 18082526
TI  - Simplifying the estimation of jugular venous pressure.
AB  - The classic technique of estimating jugular venous pressure, with variable
      inclination of the upper body and the sternal angle as the reference point, is
      complicated and little used in general practice. The aim of this prospective,
      comparative study was to assess whether estimating neck vein distension with the
      patient in the sitting position could be used to detecting elevated venous
      pressure. Patients (n = 96) who underwent right-sided cardiac catheterization or
      endomyocardial biopsy were evaluated. The visible height of the right internal
      jugular venous column above the clavicle was estimated, and the mean pressure in
      the right atrium or superior vena cava at cardiac catheterization was measured.
      Invasive venous pressure was elevated (>8 mm Hg) in 23 patients. A deep venous
      column visibly distended above the right clavicle in the sitting position had
      sensitivity of 65% and specificity of 85% to identify truly elevated venous
      pressure. Abdominal compression increased sensitivity to 77% but decreased
      specificity to 68%. In conclusion, studying the deep neck veins of a sitting
      patient simplifies the estimation of jugular venous pressure and has moderate to
      high diagnostic performance in detecting elevated central venous pressure.

PMID- 18082527
TI  - Survey of current practices of the specialty of physicians interpreting cardiac
      and noncardiac findings of coronary computed tomographic angiography.
AB  - Computed tomographic angiography, as an imaging modality to evaluate the coronary
      arteries, has been rapidly expanding since the release of 64-slice machines.
      Little is known about current practice patterns. This study was conducted to
      evaluate current practice patterns and views regarding the interpretation of
      noncardiac findings by distributing a survey to the approximately 800 attendees
      of the first annual meeting of the Society of Cardiovascular Computed Tomography
      in 2006. Of the 214 returned surveys, 16% were completed by radiologists and 82%
      by cardiologists. Ninety-nine subjects were experienced readers. At very few
      centers (9%), cardiologists read the cardiac and noncardiac portions. Few (9%)
      believed that cardiologists alone adequately interpreted noncardiac findings.
      Most subjects (72%) in the experienced and novice groups believed that the
      interpretation of noncardiac findings required input from the radiologists (p =
      0.896). In conclusion, most survey respondents believed that radiologists and
      cardiologists should be involved in interpretation of coronary computed
      tomographic angiograms. In addition, coronary computed tomographic angiography
      and computed tomography for lung cancer should not be used as a screening tool,
      although computed tomography for calcium scoring is a reasonable screening tool.

PMID- 18082528
TI  - Comparison with computed tomography of two ultrasound devices for diagnosis of
      abdominal aortic aneurysm.
AB  - Screening for abdominal aortic aneurysms (AAAs) in patients at risk will become
      more cost effective if a simple, inexpensive, and reliable ultrasound device is
      available. The aim of this study was to compare a 2-dimensional, handheld
      ultrasound device and a newly developed ultrasound volume scanner (based on
      bladder scan technology) with computed tomography (CT) for diagnosing AAA. A
      total of 146 patients (mean age 69 +/- 10 years; 127 men) were screened for the
      presence of AAAs (diameter >3 cm) using CT. All patients were examined with the
      handheld ultrasound device and the volume scanner. Maximal diameters and volumes
      were used for the analyses. AAAs were diagnosed by CT in 116 patients (80%). The
      absolute difference of aortic diameter between ultrasound and CT was <5 mm in 88%
      of patients. Limits of agreement between ultrasound and CT (-6.6 to 9.4 mm)
      exceeded the limits of clinical acceptability (+/-5 mm). An excellent correlation
      between ultrasound and CT was observed (r = 0.98). The correlation coefficient
      between the volume scanner and CT was 0.86, with agreement of 90% and kappa value
      of 0.73. Using an optimal cut-off value of >56 ml, defined by receiver-operating
      characteristic curve analysis, sensitivity, specificity, and the positive and
      negative predictive values of the volume scanner for detecting AAA were 90%, 90%,
      97%, and 71%, respectively. In conclusion, this study shows that a 2-dimensional,
      handheld ultrasound device and a newly developed ultrasound volume scanner can
      effectively identify patients with AAAs confirmed by CT.

PMID- 18082529
TI  - Echocardiographic characteristics in patients > or =100 years of age.
AB  - The centenarian population is increasing, and patients > or =100 years old are
      encountered more frequently in clinical practice. Cardiovascular disease is the
      most common cause of death in this subset of patients. We report the
      echocardiographic characteristics of 63 hospitalized centenarians. Patients
      ranged in age from 100 to 112 years and were admitted to the hospital for a
      variety of diagnoses. The mean left ventricular end-diastolic dimension was 3.9
      +/- 0.7 cm (2.8 to 5.8), the mean left ventricular end-systolic dimension was 1.8
      +/- 0.7 cm (0.8 to 3.5), the mean ventricular septal thickness was 1.2 +/- 0.25
      cm (0.8 to 1.9), the mean left ventricular posterior wall thickness was 1.1 +/-
      0.14 cm (0.8 to 1.6), the mean left ventricular ejection fraction was 84% +/- 11%
      (49% to 97%), the mean aortic root diameter at the level of the sinuses was 3.3
      +/- 0.4 cm (2.1 to 4.1), the mean left atrial dimension was 4.5 +/- 0.7 cm (3.1
      to 7), the mean right ventricular end-diastolic dimension was 3.4 +/- 0.6 cm (2.0
      to 4.8), and the mean pulmonary artery systolic pressure was 37 +/- 14 mm Hg.
      Moderate or severe valvular lesions were common, including aortic stenosis (27%),
      aortic regurgitation (17%), mitral regurgitation (22%), and tricuspid
      regurgitation (28%). In conclusion, centenarian hearts have important differences
      from younger hearts, including more hypertrophied left ventricle, higher ejection
      fraction, higher pulmonary artery systolic pressure, and more prevalent
      significant valvular heart disease.

PMID- 18082530
TI  - Heart rate and blood pressure response in adult men and women during exercise and
      sexual activity.
AB  - The purpose of this study was to assess the heart rate (HR) and blood pressure
      (BP) response of sexual activity compared with treadmill exercise in adult men
      and women. Nineteen men, 55 +/- 8 years, and 13 women, 51 +/- 7 years, underwent
      a maximal Bruce protocol treadmill stress test followed by home-monitored sexual
      activity using noninvasive HR and BP recording devices. The mean treadmill times
      were significantly shorter than the mean times of sexual activity for men and
      women (p <0.001 and p = 0.002, respectively). For the men, average maximum HR,
      systolic BP, and HR-BP product during sexual activity were 72%, 80%, and 57% of
      respective measurements during treadmill exercise. For the women, maximum HR,
      systolic BP, and HR-BP product during sexual activity were 64%, 75%, and 48% of
      respective measurements during treadmill exercise. Age correlated inversely with
      duration of treadmill exercise (a 9-second decrease in duration per increasing
      year of age; p = 0.036), and with the duration of sexual activity (a 1-minute
      decrease in duration per increasing year of age; p = 0.024). Treadmill exercise
      duration predicted sexual activity duration (a 2.3-minute increase in sexual
      activity duration per each minute treadmill duration; p = 0.026). In conclusion,
      sexual activity provides modest physical stress comparable with stage II of the
      standard multistage Bruce treadmill protocol for men and stage I for women.

PMID- 18082531
TI  - Extracardiac manifestations of infective endocarditis and their historical
      descriptions.
AB  - In his landmark "Gulstonian Lectures on Malignant Endocarditis," published in
      1885, William Osler commented, "Few diseases present greater difficulties in the
      way of diagnosis than malignant endocarditis, difficulties which in many cases
      are practically insurmountable." At that time, the fields of microbiology and
      blood cultures were in their infancy, and the diagnosis was made premortem in
      just half the patients with the condition. After Osler's report, extracardiac
      physical findings became essential clues to earlier diagnosis. Today, infective
      endocarditis is most commonly suggested from the history and often clinched by an
      echocardiogram and blood cultures. Although prized physical manifestations are
      much less frequent now, they still do occur and may be an invaluable clue that
      leads to earlier, more effective treatment. The investigators review these
      extracardiac findings along with their historical descriptions: splinter
      hemorrhages, emboli, Osler's nodes, Janeway and Bowman lesions of the eye, Roth
      spots, petechiae, and clubbing.

PMID- 18082532
TI  - The Clinical Outcomes Utilizing Revascularizaton and Aggressive Drug Evaluation
      trial: a vindication of the power of medical therapy for the secondary prevention
      of coronary heart disease.

PMID- 18082533
TI  - The late open-coronary artery hypothesis: dead, or not definitively tested?
AB  - Continued controversy surrounds the optimal therapeutic approach to the patient
      who does not undergo percutaneous coronary intervention (PCI) early during acute
      myocardial infarction, when ischemic myocardium could still be salvaged, and who
      presents days to weeks after the acute event with persistent total occlusion of
      the infarct-related coronary artery. The Occluded Artery Trial (OAT) demonstrated
      no measurable effect of PCI on outcome. There were trends, however, for more
      frequent reinfarctions and a higher estimated 4-year cumulative primary event
      rate. Because patient selection included only patients with 1- or 2-vessel
      coronary disease, and because interventionalists were permitted to perform PCI on
      the noninfarct-related arteries, >85% of patients in the intervention group had
      no coronary arteries with significant obstructions after PCI, a situation that
      would cause the functional regression of existing collaterals. If subsequent
      plaque rupture and total occlusion of any of the 3 coronary arteries occurred
      (expected in 5% to 15% of patients with acute coronary syndromes over the first 1
      to 2 years), the impaired collateral flow immediately after new acute occlusion
      would predispose to greater myocardial injury and therefore greater patient risk,
      which could explain the negative effects of the OAT study, and which raises the
      disturbing possibility that complete revascularization in patients with recent
      acute coronary syndromes could possibly lead to greater risks in the following 1
      to 2 years in those patients who experience recurrent acute coronary occlusion.
      Conversely, late opening of the culprit artery in patients with multivessel
      coronary disease, without all arteries being patent, may favorably alter late
      outcomes. In conclusion, the therapeutic implications of the OAT study apply to a
      specific patient cohort; whether late opening of the culprit artery improves or
      impairs outcome appears critically to depend on the specific cohort treated.

PMID- 18082534
TI  - Comparison of resident self-assessments with trained faculty and standardized
      patient assessments of clinical and technical skills in a structured educational
      module.
AB  - BACKGROUND: This study assessed the reliability of surgical resident self
      assessment in comparison with faculty and standardized patient (SP) assessments
      during a structured educational module focused on perioperative management of a
      simulated adverse event. METHODS: Seven general surgery residents participated in
      this module. Residents were assessed during videotaped preoperative and
      postoperative SP encounters and when dissecting a tumor off of a standardized
      inanimate vena cava model in a simulated operating room. RESULTS: Preoperative
      and postoperative assessments by SPs correlated significantly (P < .05) with
      faculty assessments (r = .75 and r = .79, respectively), but not resident self
      assessments. Coefficient alpha was greater than .70 for all assessments except
      resident preoperative self-assessments. CONCLUSIONS: Faculty and SP assessments
      can provide reliable data useful for formative feedback. Although resident self
      assessment may be useful for the formative assessment of technical skills,
      results suggest that in the absence of training, residents are not reliable self
      assessors of preoperative and postoperative interactions with SPs.

PMID- 18082535
TI  - The emotional intelligence of surgical residents: a descriptive study.
AB  - BACKGROUND: We assessed educational needs with regard to leadership,
      communication, and emotional intelligence (EI) among surgical residents. METHODS:
      General surgery residents (n = 74) were examined using the BarOn Emotional
      Quotient Inventory (EQ-i) and a 20-item survey. RESULTS: Residents believed that
      leadership skills were important (mean 4.7, SD .5) and that they had skills in
      each the five EI areas (overall mean 4.1, SD .8). Both the overall group's EQ-i
      scores (mean 106.6, SD 11.6), as well as scores on the 20 components of the EQ-i
      (range of means 102-110), were higher than national norms. Individuals varied
      substantially on EQ-i subscale scores. CONCLUSIONS: Surgical residents believed
      that leadership skills are important and scored strongly on both an EI self
      assessment and the EQ-i. Specific individual differences in subscale scores can
      potentially identify areas for direct educational intervention.

PMID- 18082536
TI  - The use of a cognitive task analysis-based multimedia program to teach surgical
      decision making in flexor tendon repair.
AB  - BACKGROUND: The aim of this study was to compare the surgical knowledge of
      residents before and after receiving a cognitive task analysis-based multimedia
      teaching module. METHODS: Ten plastic surgery residents were evaluated performing
      flexor tendon repair on 3 occasions. Traditional learning occurred between the
      first and second trial and served as the control. A teaching module was
      introduced as an intervention between the second and third trial using cognitive
      task analysis to illustrate decision-making skills. RESULTS: All residents showed
      improvement in their decision-making ability when performing flexor tendon repair
      after each surgical procedure. The group improved through traditional methods as
      well as exposure to our talk-aloud protocol (P > .01). After being trained using
      the cognitive task analysis curriculum the group displayed a statistically
      significant knowledge expansion (P < .01). CONCLUSIONS: Residents receiving
      cognitive task analysis-based multimedia surgical curriculum instruction achieved
      greater command of problem solving and are better equipped to make correct
      decisions in flexor tendon repair.

PMID- 18082537
TI  - Patient assessment and management examination: lack of correlation between
      faculty assessment and resident self-assessment.
AB  - BACKGROUND: The Patient Assessment and Management Examination (PAME) is a
      standardized patient examination designed to assess management skills of senior
      residents. This study explored the relationship between faculty and resident self
      evaluation by using PAME. METHODS: Nine postgraduate year (PGY) 4 and PGY5
      residents were examined with a 5 case PAME. Faculty rated interactions between
      residents and standardized patients and residents rated themselves based on
      review of audio-video recordings of their interactions. We examined correlations
      between faculty and resident self-assessments. RESULTS: Faculty and resident
      ratings of physical examination skills was the only competency that correlated
      significantly. Correlations were not significant for the other 15 competencies
      (Pearson r, -.197 to .262). Correlation was no better when examined within each
      case. CONCLUSIONS: Although PAME may be a useful tool, this study suggests that
      even senior residents do not assess their performance as clinicians similarly to
      faculty. Further research is needed to better understand the source of these
      disagreements.

PMID- 18082538
TI  - Assessing the teaching of procedural skills: can cognitive task analysis add to
      our traditional teaching methods?
AB  - BACKGROUND: The purpose of this study was to determine if a cognitive task
      analysis (CTA) could capture steps and decision points that were not articulated
      during traditional teaching of a colonoscopy. METHODS: Three expert colorectal
      surgeons were videotaped performing a colonoscopy. After the videotapes were
      transcribed, the experts participated in a CTA. A 26-step procedural checklist
      and a 16-step cognitive demands table was created by using information obtained
      in the CTA. The videotape transcriptions were transposed onto the procedural
      checklist and cognitive demands table to identify steps and decision points that
      were omitted during traditional teaching. RESULTS: Surgeon A described 50% of
      "how-to" steps and 43% of decision points. Surgeon B described 30% of steps and
      25% of decisions. Surgeon C described 26% of steps and 38% of cognitive
      decisions. CONCLUSIONS: By using CTA, we were able to identify relevant steps and
      decision points that were omitted during traditional teaching by all 3 experts.

PMID- 18082539
TI  - Structured assessment format for evaluating operative reports in general surgery.
AB  - BACKGROUND: Despite its multifaceted importance, no validated or reliable tools
      assess the quality of the dictated operative note. This study determined the
      construct validity, interrater reliability, and internal consistency of a
      Structured Assessment Format for Evaluating Operative Reports (SAFE-OR) in
      general surgery. METHODS: SAFE-OR was developed by using consensus criteria set
      forth by the Canadian Association of General Surgeons. This instrument includes a
      structured assessment and a global quality rating scale. Residents divided into
      novice and experienced groups viewed and dictated a videotaped laparoscopic
      sigmoid colectomy. Blinded, independent faculty evaluators graded the transcribed
      reports using SAFE-OR. RESULTS: Twenty-one residents participated in the study.
      Mean structured assessment scores (out of 44) were significantly lower for novice
      versus experienced residents (23.3 +/- 5.2 vs 34.1 +/- 6.0, t = .001). Mean
      global quality scores (out of 45) were similarly lower for novice residents (25.6
      +/- 4.7 vs 35.9 +/- 7.6, t = .006). Interclass correlation coefficients were .98
      (95% confidence interval, .96-.99) for structured assessment and .93 (95%
      confidence interval, .83-.97) for global quality scales. Cronbach alpha
      coefficients for internal consistency were .85 for structured assessment and .96
      for global quality assessment scales. CONCLUSIONS: SAFE-OR shows significant
      construct validity, excellent interrater reliability, and high internal
      consistency. This tool will allow educators to objectively evaluate the quality
      of trainee operative reports and provide a mechanism for implementing,
      monitoring, and refining curriculum for dictation skills.

PMID- 18082540
TI  - Enlarged parathyroid glands discovered in normocalcemic patients during thyroid
      surgery.
AB  - BACKGROUND: This is a retrospective study analyzing data of normocalcemic
      patients with enlarged parathyroid glands discovered during thyroid surgery and
      comparing it with data of patients operated on for proved primary
      hyperparathyroidism. METHODS: The records of patients with enlarged parathyroid
      glands (group 1) and those with primary hyperparathyroidism (group 2) were
      reviewed. RESULTS: There were 11 patients in group 1 and 123 patients in group 2.
      Enlarged parathyroid glands identified at thyroid surgery were lighter and
      developed in younger patients. Biochemistry and pathology revealed that these
      were less hyperfunctioning. Sex, number of diseased glands per patient, and cell
      type were not statistically different between the 2 groups. CONCLUSIONS: Enlarged
      parathyroid glands discovered at the time of surgery are mildly hyperfunctioning.
      They may represent an early pathologic stage responsible for overt primary
      hyperparathyroidism. We recommend removal of enlarged parathyroid glands found
      during thyroid operation in normocalcemic patients as long as at least 1 normal
      parathyroid gland remains.

PMID- 18082541
TI  - The positive effect of adenoma weight and oxyphil cell content on preoperative
      localization with 99mTc-sestamibi scanning for primary hyperparathyroidism.
AB  - BACKGROUND: Although the sensitivity of sestamibi scanning (MIBI) is high in
      patients with solitary parathyroid adenomas, negative sestamibi scan results are
      inevitable. The exact mechanism of visualization of abnormal and hyperfunctioning
      parathyroid tissue is not yet clear. The aims of this clinical study were (1) to
      evaluate positive and negative sestamibi scan results with regard to adenoma
      weight and oxyphil cell content and (2) to compare the effects of adenoma weight
      and oxyphil cell content on the results of sestamibi scanning. PATIENTS: The
      patients were divided in 2 groups according to their sestamibi scan results.
      Group 1 consisted of 27 patients with positive sestamibi scan results, and group
      2 consisted of 20 patients with negative sestamibi scan results. Parathyroid
      adenoma weight and oxyphil cell content were determined in all patients. RESULTS:
      The weight and oxyphil cell content of the parathyroid adenomas in the patients
      of group 1 were significantly higher than those in the patients of group 2 (P =
      .001). An adenoma weight >600 mg and an oxyphil cell content >20% increased the
      rate of obtaining a positive sestamibi scan result 10- and 4-fold, respectively.
      CONCLUSIONS: Both adenoma weight and oxyphil cell content were found to
      significantly correlate with positive sestamibi scan results. In patients with
      high-weight adenomas, adenoma weight was the most significant factor in obtaining
      positive MIBI scan results, whereas in patients with low adenoma weights, high
      oxyphil cell content was the most significant factor in obtaining positive MIBI
      scan results.

PMID- 18082542
TI  - Thyroid surgery: comparison between the electrothermal bipolar vessel sealing
      system, harmonic scalpel, and classic suture ligation.
AB  - BACKGROUND: This study was conducted to compare the outcome of total
      thyroidectomy using the electrothermal bipolar vessel sealing system, the
      harmonic scalpel, and the classic suture ligation technique. METHODS: This was a
      retrospective study of prospectively collected data from 382 consecutive total
      thyroidectomies from September 2004 to August 2006. Patients were divided into 3
      groups: group SL patients (n = 90) underwent total thyroidectomy with the classic
      suture ligation technique, group L (n = 148) with the electrothermal bipolar
      vessel sealer, and group U (n = 144) with the harmonic scalpel. The main outcomes
      measured were surgical and hospitalization time, intraoperative and postoperative
      bleeding, postoperative hypocalcemia, and superior and inferior laryngeal nerves
      injuries. RESULTS: The 3 groups were similar in terms of demographics, thyroid
      gland weight and pathology, perioperative complications, and hospital stay.
      Compared with the classic technique, surgical time was reduced significantly by
      about 20% when the bipolar vessel sealer or harmonic scalpel was used (93.3 +/-
      12.5 vs 74.3 +/- 14.2 and 73.8 +/- 13.8 min, P = .001, and P = .001,
      respectively). CONCLUSIONS: Both the bipolar vessel sealer and harmonic scalpel
      are safe, useful, and time-saving alternatives to the traditional suture ligation
      technique for thyroid surgery. Because no differences were observed regarding
      these 2 devices, the choice should be made based on the surgeon's preferences and
      experience.

PMID- 18082543
TI  - The effectiveness of extended lymph node dissection for gastric cancer performed
      in Costa Rica under the supervision of a Japanese surgeon: a comparison with
      surgical results in Japan.
AB  - OBJECTIVE: In 1996, the Gastric Cancer Detection Center in Costa Rica (CR)
      initiated extended lymph node (D2) dissection for gastric cancer patients. We
      present an analysis of the surgical results compared with those in Japan.
      BACKGROUND: D2 dissection for gastric cancer is a standard surgical procedure in
      Japan, whereas it is still controversial in the West because of its poor survival
      benefit and high morbidity and mortality. METHODS: Between January 1996 and March
      2000, 199 gastric cancer patients in Costa Rica underwent gastrectomy with D2
      dissection (CR group). A Japanese surgeon performed or assisted on every
      gastrectomy with Costa Rican surgeons. During the same period, 497 gastric cancer
      patients underwent D2 dissection at Tokyo Women's Medical University (TWMU),
      Tokyo, Japan (TWMU group). RESULTS: The operative morbidity was 39.0% in the CR
      group and 27.0% in the TWMU group (P < .05). The 30-day postoperative mortality
      in the CR group and the TWMU group was 5% and 0.2%, respectively (P < .05). The 5
      year survival rate in the CR group and the TWMU group was 98.0% and 99.3% in
      stage IA, 88.6% and 94.4% in stage IB, 77.8% and 76.9% in stage II, 60.1% and
      66.4% in stage IIIA, 27.2% and 47.2% in stage IIIB, and 39.7% and 27.6% in stage
      VI, respectively (not significant in any stage). The overall 5-year survival rate
      in the CR group and the TWMU group was 72.5% and 69.7%, respectively (not
      significant). CONCLUSIONS: D2 dissection performed at the same level of quality
      as in Japan consequently produced the same long-term survival in Costa Rica as in
      Japan.

PMID- 18082544
TI  - Extra-anatomic revascularization and aortic exclusion for mycotic aneurysms of
      the infrarenal aorta and iliac arteries in an Asian population.
AB  - OBJECTIVES: To study the clinical presentation, management and eventual outcome
      of patients with mycotic abdominal aortic aneurysms managed with aortic exclusion
      and extra-anatomic reconstruction. DESIGN: A retrospective chart review of 18
      cases treated at a single institution. METHODS: Medical records of 18 patients
      admitted to our institution from October 1997 to July 2006 with a diagnosis of
      mycotic abdominal aortic aneurysms were reviewed. In all cases, the diagnosis was
      confirmed by abdominal computed tomography and empirical parenteral antibiotics
      were administered. Seventeen patients had surgical debridement, aneurysm
      exclusion, and extra-anatomic reconstruction. The antibiotics were continued in
      the postoperative period for 6 weeks. RESULTS: Immunosuppression was present in
      72%, with diabetes mellitus present in 56%. Salmonella sp was the causative
      organism in 72% of cases. Most patients presented late, with a 67% incidence of
      contained rupture. Seventy-two percent needed early or emergency surgery with
      less than 1 week of preoperative antibiotics. Disease-specific mortality was 39%
      (7/18). There was 1 late death during the mean follow-up period of 34 +/- 26
      months. One patient with an infrarenal aneurysm arising relatively close (neck, 2
      cm) to the renal arteries died on table when proximal ligatures cut through the
      friable aortic wall, resulting in uncontrollable exsanguination. One third of
      patients on long-term graft surveillance developed mild to moderate stenosis at
      the anastomotic site. CONCLUSIONS: Empirical antibiotics must be started early,
      aiming to achieve 1 week of antibiotics prior to surgery. In the Asian
      population, 3 characteristics are apparent: (1) most patients are
      immunocompromised; (2) patients present late in the course of disease; and (3)
      Salmonella is usually responsible. Extra-anatomic bypass may provide a safe
      option for revascularization of mycotic aneurysms of the iliac arteries and
      infrarenal aorta.

PMID- 18082545
TI  - Functional outcomes of two types of subtotal colectomy for slow-transit
      constipation: ileosigmoidal anastomosis and cecorectal anastomosis.
AB  - BACKGROUND: Some patients with severe slow-transit constipation may benefit from
      subtotal colectomy, but there is no consensus on standard operative mode. The aim
      of the study was to compare the functional outcomes of subtotal colectomy with
      cecorectal anastomosis (CRA) with those of subtotal colectomy with ileosigmoidal
      anastomosis (ISA) in patients with severe slow-transit constipation. METHODS:
      Records of 79 patients who received preoperative investigation to confirm slow
      transit at our institution from 1989 to 2004 and subsequently received colectomy
      with CRA (n = 34) or colectomy with ISA (n = 45) were reviewed. The mean follow
      up was 2 years (range 1-15). RESULTS: Postoperative defecation frequency
      increased and symptoms such as bloating and abdominal pain decreased in both
      groups. More CRA patients than ISA patients experienced persistent constipation
      and continued using laxatives or enemas at the 12-month follow-up. More ISA
      patients (93.3%) than CRA patients (73.5%) were satisfied with the procedure,
      whereas some patients in both groups complained of excessively high stool
      frequency and fecal incontinence. CONCLUSION: Both CRA and ISA procedures
      increase the number of bowel movements; however, ISA results in higher defecation
      frequency, less use of laxatives and enemas, and higher patient satisfaction.

PMID- 18082546
TI  - Trauma patients: you can get them in, but you can't get them out.
AB  - BACKGROUND: The majority of inpatient trauma care resources are consumed by a
      small proportion of severely injured patients. METHODS: Hospital lengths of stay
      (LOS), resource consumption, and postdischarge placement were abstracted from the
      institutional trauma registry. RESULTS: Patients (n = 4,070) were evaluated by
      the trauma service during the study period. The overall mean LOS was 4.4 days,
      and beds were occupied on 18,005 days. Two hundred forty-four (6%) patients
      remained in the hospital >14 days after injury and occupied beds on 8,560 (47%)
      days. These patients were older, more severely injured, and required
      proportionately more intensive care unit and operative care. Injuries to the
      head, abdomen, and extremities were independently associated with longer LOS.
      Most patients with longer LOS were placed in long-term acute care or received
      home nursing care after discharge. CONCLUSIONS: Almost half of inpatient trauma
      bed-days are occupied by a small proportion of patients with long-term care
      needs.

PMID- 18082547
TI  - Staged repair of massive incisional hernias with loss of abdominal domain: a
      novel approach.
AB  - BACKGROUND: The management of massive ventral hernias with loss of intra
      abdominal domain is a challenging surgical dilemma. We report a novel approach
      for repairing these extremely complicated hernias. METHODS: We retrospectively
      reviewed our experience with the staged resection of Gore Tex Dual mesh (WL Gore
      and Associates, Flagstaff, AZ) in the setting of massive abdominal wall defects.
      The initial stage involves reduction of the hernia and placement of a large sheet
      of Gore Tex Dual mesh secured to the fascial edges. Subsequent stages involve
      serial excision of the mesh until the fascia can be approximated in the midline
      without tension. Finally, the mesh is excised, and the fascia is reapproximated
      with component separation and AlloDerm (Lifecell Corporation, Branchburg, NJ)
      underlay. RESULTS: We have performed this procedure on 8 patients, with a mean
      age of 53 years (range 35-76). All patients had multiply recurrent ventral
      hernias with an average of 4.3 prior laparotomies (range 2-9). The fascial defect
      averaged 535 cm2 (300-884 cm2), and on average 6 serial operations were necessary
      to achieve fascial closure. The average length of stay was 36 days (range 9-90).
      One patient developed a postoperative wound infection requiring operative
      debridement, and 1 recurrence was identified during follow-up after an early
      wound complication. CONCLUSIONS: Serial Gore-Tex excision to facilitate primary
      fascial closure with AlloDerm sublay is an effective treatment for massive,
      incisional hernias with loss of abdominal domain and avoids the risks associated
      with long-term prosthetic fascial closures.

PMID- 18082548
TI  - Long-term changes in weight loss and obesity-related comorbidities after Roux-en
      Y gastric bypass: a primary care experience.
AB  - BACKGROUND: Long-term results of Roux-en-Y gastric bypass (RYGB) are nonexistent
      in the veterans affairs (VA) population. We compare excess weight loss (EWL)
      success and medical comorbidity changes between the VA and non-VA population
      after RYGB. METHODS: Retrospective review of consecutive subjects undergoing RYGB
      from 1997 to 2002 at the Los Angeles VA. Weight and comorbidity data were
      collected every 6 and 12 months, respectively. RESULTS: Fifty-nine subjects were
      included; 54%, 58%, 46.8%, and 44.1% of subjects achieved EWL >50% at years 1 to
      4. Hypertension resolved in 23%, 30%, and 32% at months 12 to 36. Obstructive
      sleep apnea resolved in 37%, 48%, 48%, 44%, and 60% at months 12 to 60. Diabetes
      mellitus resolved in 86%, 84%, 79%, and 80% at months 12 to 48. Improvements in
      the lipid panel were observed by month 12 and maintained thereafter. CONCLUSIONS:
      EWL and proportion of subjects with resolved hypertension and obstructive sleep
      apnea are inferior to the non-VA population. Nevertheless, improvements in
      measures of success are maintained in the VA population.

PMID- 18082549
TI  - Aneurysmal bone cyst originating from the first rib.
AB  - Aneurysmal bone cyst is a benign tumor of the skeletal system and rare in the
      ribs. A 25-year-old woman was found to have an abnormal shadow in the left chest
      on the radiologic examinations. The first rib containing tumor was removed.
      Pathologic findings showed an aneurysmal bone cyst.

PMID- 18082550
TI  - Obstructing phytobezoar arising from proximal jejunal diverticulum.
AB  - The following report illustrates a rare case of small bowel obstruction which
      occurred when a large phytobezoar, which had formed in a proximal jejunal
      diverticulum, dislodged and migrated distally. Obstruction and subsequent
      perforation resulted when the phytobezoar passed into the narrow terminal ileum
      and lodged just proximal to the ileocecal valve. The images are presented for
      educational purposes.

PMID- 18082551
TI  - Open cholecystectomy in the laparoendoscopic era.
AB  - Laparoscopic cholecystectomy has all but replaced the traditional open approach.
      Hence open cholecystectomy (OC) is principally reserved for cases in which
      laparoscopy fails, leaving fewer surgeons with experience in the procedure
      required for the most challenging cases. This review of OC includes discussion of
      the indications for a primary open approach, conversion from laparoscopy,
      technical aspects of OC, and alternatives (cholecystostomy and subtotal
      cholecystectomy). Strategies for safe OC must be formally addressed in residency
      programs.

PMID- 18082552
TI  - Choledochojejunostomy revision performed by using the laparoscopic linear cutter.
AB  - Choledochojejunostomy is commonly performed for biliary bypass for benign and
      malignant disease. Anastomotic stricture is a known complication of enteric
      surgery. We report the use of the laparoscopic linear cutter at laparotomy to
      revise a choledochojejunostomy created 12 years previously for benign disease.

PMID- 18082554
TI  - The impact of prophylactic antibiotics on postoperative infection complication in
      elective laparoscopic cholecystectomy: a prospective randomized study.

PMID- 18082553
TI  - Two-channel gastric pacing with a novel implantable gastric pacemaker accelerates
      glucagon-induced delayed gastric emptying in dogs.
AB  - BACKGROUND: The aim of the current study was to investigate the efficacy of 2
      channel gastric electrical stimulation (GES) with a custom-made implantable
      pacemaker on delayed gastric emptying and gastric dysrhythmia induced by glucagon
      in dogs. METHODS: Six dogs were studied in 4 randomized session (saline,
      glucagon, glucagon with single-channel or 2-channel GES). GES was applied via the
      first pair of electrodes for single-channel GES or the first and third pairs of
      electrodes for 2-channel GES. Gastric emptying was assessed for 90 minutes and
      gastric slow waves were recorded at the same time. RESULTS: Both single-channel
      and 2-channel GES improved gastric dysrhythmia (P < .05 vs glucagon session). Two
      channel GES but not single-channel GES improved glucagon-induced delayed gastric
      emptying at 30 minutes, 45 minutes, 60 minutes, 75 minutes, and 90 minutes.
      CONCLUSION: Two-channel GES with a novel implantable pacemaker is more efficient
      and effective than single-channel GES in improving delayed gastric emptying
      induced by glucagon. This implantable multipoint pacemaker may provide a new
      option for treatment of gastric motility disorders.

PMID- 18082555
TI  - Glycine transport inhibitors and the treatment of schizophrenia.

PMID- 18082557
TI  - The 2007 Recommendations of the International Commission on Radiological
      Protection. ICRP publication 103.
AB  - These revised Recommendations for a System of Radiological Protection formally
      replace the Commission's previous, 1990, Recommendations; and update,
      consolidate, and develop the additional guidance on the control of exposure from
      radiation sources issued since 1990. Thus, the present Recommendations update the
      radiation and tissue weighting factors in the quantities equivalent and effective
      dose and update the radiation detriment, based on the latest available scientific
      information of the biology and physics of radiation exposure. They maintain the
      Commission's three fundamental principles of radiological protection, namely
      justification, optimisation, and the application of dose limits, clarifying how
      they apply to radiation sources delivering exposure and to individuals receiving
      exposure. The Recommendations evolve from the previous process-based protection
      approach using practices and interventions by moving to an approach based on the
      exposure situation. They recognise planned, emergency, and existing exposure
      situations, and apply the fundamental principles of justification and
      optimisation of protection to all of these situations. They maintain the
      Commission's current individual dose limits for effective dose and equivalent
      dose from all regulated sources in planned exposure situations. They reinforce
      the principle of optimisation of protection, which should be applicable in a
      similar way to all exposure situations, subject to the following restrictions on
      individual doses and risks; dose and risk constraints for planned exposure
      situations, and reference levels for emergency and existing exposure situations.
      The Recommendations also include an approach for developing a framework to
      demonstrate radiological protection of the environment.

PMID- 18082565
TI  - Assessing the function of human UNC-93B in Toll-like receptor signaling and major
      histocompatibility complex II response.
AB  - The high sequence identity observed between UNC-93B of mouse and human imply
      common evolutionary ancestors and a conserved function. A nonconservative point
      mutation in the mouse Unc93b1 gene has been associated with defective Toll-like
      receptor (TLR) signaling and impaired major histocompatibility complex (MHC) I
      and II restricted antigen responses. Like murine UNC-93B, the human homologue is
      predicted to form 12 transmembrane domains, and it localizes to the endoplasmic
      reticulum. In human beings its expression is highest in professional antigen
      presenting cells such as dendritic cells and macrophages. Interestingly, UNC-93B
      itself is specifically induced by TLR3 signaling in monocyte-derived dendritic
      cells and macrophages. To study the effect of UNC-93B deficiency in TLR signaling
      and antigen-presentation in human beings, UNC-93B message was knocked down in
      monocyte-derived dendritic cells and a reduced TNFalpha production in response to
      TLR3 agonists was observed. In the same experiment, the achieved knockdown had no
      effect on an MHC II-dependent antigen response, suggesting that the reduced
      quantity of human UNC-93B was still capable of supporting class II antigen
      presentation or that UNC-93B is not required for class II antigen presentation in
      human antigen-presenting cells.

PMID- 18082566
TI  - Inhibitory oligodeoxynucleotides downregulate herpes simplex virus-induced
      plasmacytoid dendritic cell type I interferon production and modulate cell
      function.
AB  - Recognition of nucleic acids by TLR9 expressed by human plasmacytoid dendritic
      cells (PDC) plays a key role in the defense against viral infections. Upon
      microbial pathogen stimulation, PDC secrete large amounts of type I interferon
      and arbitrate thereby both innate and adaptive immune mechanisms. Unmethylated
      CpG motifs, which are an integral part of bacterial or viral DNA, are used in
      vitro and in vivo to activate the TLR9 pathway, whereas inhibitory
      oligodeoxynucleotide (iODN) are capable of depressing TLR9 signaling. In this
      study we demonstrate that TTAGGG motifs containing iODN efficiently block the
      TLR9 signaling in terms of herpes simplex virus (HSV)-induced type I interferon
      production by PDC. However, iODN, as well as control ODN, still promote PDC
      maturation with upregulated expression of costimulatory molecules, major
      histocompatibility complex molecules, and other signs for PDC maturation.
      Furthermore, iODN and control ODN incubated PDC demonstrate increased T-cell
      stimulatory functions. Coculture experiments with autologous T cells indicate
      that iODN-treated PDC induce more CD4(+)CD25(+)Foxp3(+) T regulatory cells from
      naive CD4(+) T cells and preincubation of HSV-stimulated PDC with iODN
      upregulated T cells' IFN-gamma production. These data indicate that iODN, while
      blocking type I interferon production by PDC, modify PDC activation and
      maturation as well as T-cell priming and stimulation. Knowledge about the
      different functions of iODN on PDC elucidated might be crucial for
      immunotherapeutic strategies in which iODN motifs are used to prevent the
      interaction of CpG-DNA with TLR9 to calm down specific immunological responses,
      because our data indicate that iODN might not only have inhibitory functions but
      also be effective activators of immune cells.

PMID- 18082567
TI  - Mannose-binding lectin genotypes and pre-eclampsia: a case-control study.
AB  - Both immunological and placental factors are involved in the pathogenesis of pre
      eclampsia. The complement factor mannose-binding lectin (MBL) is associated with
      adverse pregnancy outcomes and has been suggested to play a role in abnormal
      placentation. We investigated whether MBL genotypes are associated with the
      systemic maternal syndrome pre-eclampsia. MBL2 gene polymorphisms were determined
      in a case-control study including 157 women with pre-eclampsia (case subjects)
      and 157 women with uncomplicated pregnancies (control subjects). Considering MBL
      polymorphisms, case and control subjects were categorized in groups of high (A),
      intermediate (B), and low (C) MBL production. No association was found between
      MBL genotypes and pre-eclampsia; adjusted odds ratios and 95% confidence
      intervals (95% CI) for group B were 0.97 (95% CI = 0.46-2.07) and for group C
      were 1.44 (95% CI = 0.52-3.94). A trend was found between MBL genotype groups B
      and C and severe pre-eclampsia or eclampsia. MBL genotypes were not found to be
      associated with pre-eclampsia; however low-MBL production genotypes might be
      considered as disease modifier. This suggests that MBL may play a role in
      modulating placental inflammation by facilitating clearance of apoptotic cells
      and cell debris.

PMID- 18082568
TI  - Behavior of serum human major histocompatibility complex class I antigen levels
      in human immunodeficiency virus-infected patients during antiretroviral therapy:
      correlation with clinical outcome.
AB  - Human major histocompatibility complex class I antigens (HLA-A, -B, and -C) are
      heterodimeric molecules composed of a alpha heavy chain noncovalently associated
      with an invariant protein known as beta(2)-microglobulin. Beside being expressed
      on the membrane of the large majority of nucleated cells, HLA class I antigens
      are evident in serum (sHLA-I). We have previously detected a significant increase
      in the serum level of beta(2)-microglobulin-associated HLA-I antigens in human
      immunodeficiency virus (HIV)-infected patients compared with HIV-negative
      controls. The introduction of highly active antiretroviral therapy (HAART)
      modified the clinical course of the disease and decreased the acquired
      immunodeficiency syndrome-related morbidity and mortality. Therefore, we measured
      the levels of sHLA-I antigens in 64 HIV-infected patients before and during HAART
      treatment and correlated them with the immunological and virological response to
      antiretroviral treatment. Serum sHLA-I antigen level was elevated in all HIV
      infected patients before and significantly decreased after 36 months of HAART
      treatment, correlating with the decrease of plasma HIV-RNA level and with the
      increase of CD4+ T-lymphocyte number. These results suggest that the measurement
      of sHLA-I antigens serum level might represent a useful surrogate marker to
      monitor HIV-positive patients undergoing HAART treatment.

PMID- 18082569
TI  - Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms
      with gastritis and precancerous lesions.
AB  - A Toll-like receptor-4 (TLR-4) Asp299Gly and Thr399Ileu substitution reduces
      responsiveness to Helicobacter pylori (H. pylori) lipopolysaccharide. CagA+
      strains of H. pylori are known to be associated with gastroduodenal diseases.
      Therefore we aimed to evaluate association of TLR-4 substitutions and CagA
      seropositivity with gastritis and precancerous lesions in a northern Indian
      population. After upper gastrointestinal endoscopy, 130 rapid urease test (RUT)
      positive patients with nonulcer dyspepsia (NUD) were included. Patients with NUD
      were also screened for H. pylori infection using modified Giemsa staining and
      anti-CagA IgG enzyme-linked immunoabsorbent assay. All patients and 200
      asymptomatic control subjects were genotyped for TLR-4 substitutions using
      polymerase chain reaction-restriction fragment length polymorphism. We observed
      that frequencies of TLR-4 Asp299Gly variants were comparable between patients and
      control subjects, and also between positive and negative groups of precancerous
      lesions in patients. Frequencies of TLR-4 399Ileu allele (8% vs 3%, p = 0.008)
      and Asp299-Ileu399 haplotype (6.5% vs 3%, p = 0.022) were higher in patients than
      in control subjects at risk for gastritis (OR = 2.6 and 2.5, respectively). TLR-4
      399Ileu allele carriers had higher risk for plasma cell infiltration (p = 0.023,
      OR = 10.6) that led to atrophy (p = 0.028, OR = 4.2) and intestinal metaplasia (p
      = 0.009, OR = 4.7). CagA positivity was more frequently associated with lymphoid
      follicle formation (p = 0.033, OR = 2.53). In conclusion TLR-4 Thr399Ileu
      substitution may be a risk factor for gastritis and precancerous lesions. CagA
      positivity may be a risk factor for lymphoid follicle development but not for
      other precancerous lesions in a northern Indian population.

PMID- 18082570
TI  - Promoter and neck region length variation of DC-SIGN is not associated with
      susceptibility to tuberculosis in Tunisian patients.
AB  - The C-type lectin DC-SIGN (CD209) is an important pathogen recognition receptor
      of the innate immune system. Recent studies showed that DC-SIGN is the major
      receptor of Mycobacterium tuberculosis on human dendritic cells and that
      polymorphisms in the DC-SIGN promoter region are associated with susceptibility
      to tuberculosis. In this light, we aimed to study the potential implication of DC
      SIGN genetic variation in the predisposition to tuberculosis in a group of
      Tunisian patients. We thus performed an association study comprising 138
      tuberculosis patients and 140 healthy controls. Sequencing of the DC-SIGN
      promoter region detected four polymorphisms (-939, -871, -601, and -336), but no
      differences in their allelic distribution were observed between the two groups.
      In addition, the analysis of length variation in the DC-SIGN neck region
      indicated extremely low levels of polymorphisms and, again, no differences
      between patients and controls. Our data showed therefore that neither promoter
      variants nor length variation in the neck region of DC-SIGN is associated with
      susceptibility to tuberculosis in Tunisian patients.

PMID- 18082571
TI  - Description of HLA-A*0127N, a novel nonexpressed allele identified by SBT.
AB  - We describe the isolation and characterization of a novel HLA-A null allele,
      officially named A*0127N. The A*0127N exon 2, 3, and 4 nucleotide sequence is
      identical to that of A*010101 except at position 553, where a G is substituted by
      a T, resulting in a coding change in exon 3 (GAG>TAG) from Glu to the stop codon
      AMB. The mutation described is responsible for the premature ending of the
      translation.

PMID- 18082572
TI  - High-throughput sequence-based typing strategy for HLA-DRB1 based on real-time
      polymerase chain reaction.
AB  - DNA sequencing is the gold standard for high-resolution genotyping of the highly
      polymorphic human leukocyte antigen (HLA) loci. In the case of hematopoietic stem
      cell transplantation, four-digit typing of HLA class I and II genes is indicated.
      We developed a group-specific, real-time polymerase chain reaction (PCR) strategy
      for amplification of DRB1 applying TaqMan chemistry on different real-time
      machines. For evaluation of genotyping accuracy and ambiguity resolution, 115
      well-characterized samples were adapted. Separate analysis of each allele was
      possible in 100 samples (87%). Of the samples, 13% (n = 15) showed amplification
      in one of the eight group-specific PCR mixes: one sample according to the group
      DRB1*15, 16, along with 14 samples according to the group DRB1*03, *11, *13, *14.
      Further testing of the 14 (12.2%) samples associated with group DRB1*03, *11,
      *13, *14 was performed with specific intron primers. In conclusion this typing
      scheme generates results within 1 day, thereby making sequencing for different
      requirements attractive.

PMID- 18082573
TI  - HLA class I polymorphism in the Cuban population.
AB  - The extreme polymorphism found at some of the human leukocyte antigen (HLA)
      system loci makes it an invaluable tool for population genetic analyses. In the
      present study the genetic polymorphism of the Cuban population was estimated at
      HLA-A, -B, and -Cw loci by DNA typing. HLA class I allele and haplotype diversity
      were determined in 390 unrelated Cuban individuals (188 whites and 202 mulattos)
      from all over the country. In whites 19, 27, and 14 allele families for the HLA
      A, -B, and -Cw loci, respectively, were identified. In mulattos, for the same
      loci, 20, 18, and 14 allele families were identified. Allele and haplotypes
      frequencies, comparisons with other worldwide populations based on genetic
      distances, neighbor-joining dendrograms, and correspondence analyses were
      estimated. Most of the identified allele groups and haplotypes are also common to
      sub-Saharan African and Europeans populations. However, Amerindian and Asian
      alleles were also detected at lower frequencies. The results clearly reveal the
      high diversity and interethnic admixture of the studied population. Our results
      provide useful information for the further studies of the Cuban population
      evolution and disease association in terms of HLA class I genes.

PMID- 18082574
TI  - Human leukocyte antigen class I polymorphism in Miao, Bouyei, and Shui ethnic
      minorities of Guizhou, China.
AB  - The majority of Miaos, Bouyeis, and Shuis are distributed in the Guizhou province
      of southwest China. They live within vast areas, while each ethnicity lives in
      individual concentrated communities in small areas. Their origin, migration, and
      relationship have long been interesting to anthropologists. In the present study,
      polymorphism of HLA-A, -B, and -C genes was investigated using the sequencing
      based typing method in the Miao, Bouyei, and Shui from Guizhou, southwest China.
      Generally, Miao, Bouyei, and Shui share the most high-frequency alleles,
      suggesting that these three ethnic groups might be subject to intensive gene
      exchange because of their close location. However, it appears that some alleles
      distribute ethnic-specifically for each ethnicity. The dendrogram constructed
      according to the neighbor-joining method demonstrates that Miao, Bouyei, and Shui
      cluster together and form a branch with other southern Chinese ethnic groups,
      indicating that Miao, Bouyei, and Shui are three genetically close ethnic groups
      and inherit more characteristics of southern Chinese populations. The study will
      increase our understanding of the HLA polymorphism in Chinese populations.

PMID- 18082579
TI  - Strategies to prevent unrecognised oesophageal intubation during out-of-hospital
      cardiac arrest.

PMID- 18082575
TI  - The autoimmune disease-associated IL12B and IL23R polymorphisms in multiple
      sclerosis.
AB  - Recently published genetic studies in psoriasis, inflammatory bowel disease, and
      ankylosing spondylitis identified significant associations with IL12B and IL23R
      polymorphisms. An important role for the IL-12/IL-23 pathway in multiple
      sclerosis (MS) is supported by immunologic studies in patients and animal models.
      To determine whether IL12B/IL23R disease-associated polymorphisms play a role in
      susceptibility to MS, we genotyped 910 MS-nuclear families, totaling 3132
      individuals. Family-based association analysis was performed. There was no
      evidence of transmission distortion of any of the tested alleles in this data
      set.

PMID- 18082580
TI  - Microbial genomics.

PMID- 18082582
TI  - Active surveillance for favorable risk prostate cancer: what are the results, and
      how safe is it?
AB  - Active surveillance for favorable risk prostate cancer has become increasingly
      popular in populations in which prostate cancer screening is widespread because
      of evidence that prostate cancer screening results in the detection of disease
      that is not clinically significant in many patients (ie, untreated, would not
      pose a threat to health). The approach is supported by data showing that patients
      who fall into the category of clinically insignificant disease can be identified
      with reasonable accuracy and that patients who are initially classified as low
      risk who reclassify over time as higher risk and are treated radically are still
      cured in most cases. This means (1) identifying patients who have a low
      likelihood of disease progression during their lifetime based on clinical and
      pathologic features of the disease and patient age and comorbidity, (2) close
      monitoring over time, (3) reasonable criteria for intervention that will both
      identify more aggressive disease in a timely fashion and not result in excessive
      treatment, and (4) meeting the communication challenge to reduce the
      psychological burden of living with untreated cancer. The results of active
      surveillance, the criteria for patient selection, and the appropriate triggers
      for intervention are reviewed.

PMID- 18082583
TI  - Hormone therapy and radiotherapy for intermediate risk prostate cancer.
AB  - The optimal therapy for prostate cancer classified as "intermediate risk" on the
      basis of prostate-specific antigen, Gleason score, and clinical T stage is
      currently evolving. The role of hormonal therapy in these patients remains
      controversial, particularly in the setting of dose-escalated radiation. In this
      review, we examine the currently available data and describe maturing studies
      that address the optimal timing, duration, and potential risks and benefits of
      adding hormonal therapy to external-beam radiation for intermediate-risk
      patients. We conclude that until additional data become available, a short course
      of androgen deprivation, concurrent with radiation, should be considered in
      selected intermediate-risk patients who may be at greatest risk for failure if
      treated with external-beam radiation alone.

PMID- 18082584
TI  - Postprostatectomy radiation therapy for prostate cancer.
AB  - Radical prostatectomy is the most common initial treatment for prostate cancer.
      Patients with high-risk pathologic features, such as a positive margin or seminal
      vesicle involvement, have a 40% to 50% risk of developing biochemical failure at
      some point in the future. Radiotherapy to the prostate bed has been used both
      adjuvantly and for salvage. There continues to be an active debate regarding when
      radiation should be administered, although 3 recent randomized trials show a
      consistent improvement in biochemical failure when adjuvant radiotherapy is
      administered as compared with radical prostatectomy alone. Because the morbidity
      of postoperative radiotherapy is relatively low, when pathologic high risk
      factors are present adjuvant radiotherapy should be considered. The role of
      androgen deprivation postprostatectomy is less well defined.

PMID- 18082585
TI  - Combined permanent implant and external-beam radiation therapy for prostate
      cancer.
AB  - A number of series have been published examining the utility of combining low
      dose rate permanent interstitial implants with external-beam radiation (CMT).
      However, the data show conflicting results. Comparisons of these studies are
      confounded by the lack of similar biochemical failure definitions, inequities in
      risk groups between compared arms, variable implant quality, and differences in
      implant margins and techniques. Despite these limitations, the literature does
      suggest that CMT may help spare patients the need for androgen deprivation,
      overcome adverse pathologic factors, and correct for poor implant quality. We
      present the recent innovation and potential benefits of using implant dose
      adjusted intensity-modulated radiation therapy.

PMID- 18082586
TI  - Pelvic lymph node irradiation for prostate cancer: who, why, and when?
AB  - Prostate cancers are best characterized by their clinical (TNM) stage, Gleason
      score, and serum prostate-specific antigen (PSA) level. These 3 factors are known
      to influence the risk of pelvic nodal involvement. By combining these prognostic
      factors, nomograms and equations have been developed and are widely used in
      clinical practice as an accurate way of predicting the probability of a given
      pathological stage. Patients who have a significant risk of pelvic nodal
      metastasis will likely have higher biochemical failure rates. Results from the
      multi-institutional prospective trials have shown that patients at an
      intermediate to high risk for pelvic nodal involvement experience disease
      progression-free survival benefits from the use of whole pelvic radiotherapy
      combined with hormone therapy. Yet, significant biological interactions between
      radiation treatment volumes and timing of hormone therapy have been shown.
      Further study of these issues is necessary to define the best treatment for
      patients at significant risk of pelvic lymph node involvement.

PMID- 18082587
TI  - Hypofractionation for prostate cancer: a critical review.
AB  - In ideal circumstances, the fractionation schedule of radiotherapy should match
      the fractionation sensitivity of the tumor relative to the nearby normal tissues.
      A number of recent publications have suggested that the alpha-beta ratio
      (alpha/beta) for prostate is low, in the range of 1 to 3 Gy. If alpha/beta is
      truly low, then hypofractionated schedules using fewer, larger fractions should
      improve the therapeutic ratio. This critical review examines the clinical
      experience with hypofractionation. Several prospective trials indicate that
      toxicity is limited with sophisticated dose delivery and compact clinical target
      volume to planning target volume margins, but the single-arm nature of these
      trials precludes definitive statements on efficacy. Several large randomized
      trials comparing conventional fractionation to hypofractionation are ongoing and
      are described. Until these trials are completed and the results submitted for
      rigorous peer review, the notion that alpha/beta for prostate cancer is low
      remains an unconfirmed hypothesis.

PMID- 18082588
TI  - Intensity-modulated radiation therapy: supportive data for prostate cancer.
AB  - Since its introduction into clinical use in the mid-1990s, intensity-modulated
      radiation therapy (IMRT) has emerged as the most effective and widely used form
      of external-beam radiotherapy for localized prostate cancer. Multiple studies
      have confirmed the importance of delivering sufficiently high doses to the
      prostate to achieve cure. The dosimetric superiority of IMRT over conventional
      techniques to produce conformal dose distributions that allow for organ sparing
      has been shown. A growing number of reports have confirmed that IMRT is the
      safest way to deliver high doses of external-beam irradiation to the prostate and
      the regional lymph nodes. Advances in imaging and onboard verification systems
      continue to advance the capabilities of IMRT and have potential implications with
      regards to further dose escalation and hypofractionated regimens. The clinical
      data in support of IMRT and the associated technical aspects of IMRT treatment
      planning and implementation are highlighted in this review.

PMID- 18082589
TI  - Image-guided radiotherapy for localized prostate cancer: treating a moving
      target.
AB  - Prostate motion during external-beam radiotherapy can affect outcomes in patients
      with localized prostate cancer. Prostate motion and deformation are currently
      being characterized with different techniques. There is significant individual
      variation among patients with respect to the observed motion and its dosimetric
      consequences. There is also significant difference in the accuracy of different
      localization methods currently used to adjust for prostate motion. The motion of
      the prostate gland can itself affect the accuracy of different localization
      methods. The dosimetric impact on target areas and organs at risk should be
      studied for different localization techniques, treatment plan margins, and
      treatment schedules. Such assessments will be increasingly important with smaller
      treatment margins, smaller fraction numbers, and higher radiation doses.
      Understanding and managing the consequences of anatomic variations within the
      lower pelvis should be a priority in designing and implementing future clinical
      trials.

PMID- 18082590
TI  - Measuring health-related quality of life consequences from primary treatment for
      early-stage prostate cancer.
AB  - Radical prostatectomy, external radiation therapy, and brachytherapy are all
      mainstay treatment options for clinically localized prostate cancer. Over time,
      each of these treatments has been modified so as to maximize percent cancer-free
      survival while minimizing health-related risks such as urinary incontinence,
      bowel incontinence, and sexual dysfunction. With these efforts, there is still
      not one superior single treatment that is devoid of side effects. Concurrently,
      efforts have been made to generate validated health-related quality of life
      (HRQOL) measurement scales to aid in the decision making by both physician and
      patient. HRQOL measurement scales enable physicians to have informed discussions
      with patients about potential likelihood of a given set of side effects with the
      various prostate cancer treatment options. This review will highlight prostate
      cancer HRQOL outcomes and delineate further areas of study necessary to optimize
      evidence-based decision making for prostate cancer patients.

PMID- 18082591
TI  - Three drug indications for patients with peripheral arterial disease bite the
      dust: report from the American Heart Association meeting 2007 in Orlando.

PMID- 18082594
TI  - Paradigms for the three rs: DNA replication, recombination, and repair.
AB  - The recent decade has engendered a convergence of the otherwise distinct fields
      of DNA replication, recombination, and repair, as we are learning how these
      essential transactions can operate in coordination to achieve genomic stability
      and to ensure cellular viability. In the next decade, we can anticipate a
      functional understanding of the roles of posttranslational protein modifications
      in the regulation and prioritizing of pathways for genomic maintenance. The
      fundamental knowledge gained should lead to more effective clinical intervention
      in human disease.

PMID- 18082595
TI  - Gene regulation in the postgenomic era: technology takes the wheel.
AB  - Transcriptional regulation in eukaryotes is a complicated set of processes
      involving hundreds of proteins. The past decade has seen significant progress in
      the development of technologies that allow the dissection of the interplay
      between these regulatory factors. These methodologies have advanced the field to
      the point where regulation can be examined at the genome level and where
      intricate regulatory questions can be addressed in multicellular organisms. The
      application of these technologies over the coming decade promises exciting views
      of how complexes integrate to create defined regulatory networks.

PMID- 18082596
TI  - RNA 1997-2007: a remarkable decade of discovery.
AB  - The past decade has witnessed spectacular progress in the field of RNA biology
      and biochemistry; old problems have been solved, and new ones have emerged. This
      perspective briefly reviews where we are today and where we might be 10 years
      hence.

PMID- 18082597
TI  - New modes of translational control in development, behavior, and disease.
AB  - Over the last 10 years, the field of translational control has been enriched by
      atomic resolution structures of ribosomal complexes and factors in different
      functional states, and increased in sophistication by wedding genetics,
      reconstituted systems, and structural biology to elucidate basic reactions and
      mRNA-specific control mechanisms. New regulatory principles have emerged,
      including repression by micro-RNAs (miRNAs) and mRNA sequestration in cytoplasmic
      granules, and the field has extended its reach into development, brain function,
      and human disease. Here we seek to highlight some of the exciting developments of
      the last decade from the perspectives of our own approaches and expertise;
      accordingly, many highly noteworthy achievements could not be mentioned and we
      refer interested readers to the numerous excellent reviews cited below.

PMID- 18082598
TI  - The age of crosstalk: phosphorylation, ubiquitination, and beyond.
AB  - Crosstalk between different types of posttranslational modification is an
      emerging theme in eukaryotic biology. Particularly prominent are the multiple
      connections between phosphorylation and ubiquitination, which act either
      positively or negatively in both directions to regulate these processes.

PMID- 18082599
TI  - The DNA damage response: ten years after.
AB  - The DNA damage response (DDR), through the action of sensors, transducers, and
      effectors, orchestrates the appropriate repair of DNA damage and resolution of
      DNA replication problems, coordinating these processes with ongoing cellular
      physiology. In the past decade, we have witnessed an explosion in understanding
      of DNA damage sensing, signaling, and the complex interplay between protein
      phosphorylation and the ubiquitin pathway employed by the DDR network to execute
      the response to DNA damage. These findings have important implications for aging
      and cancer.

PMID- 18082600
TI  - Lucifer's labyrinth--ten years of path finding in cell death.
AB  - Cell death, as a foil to cell expansion, has become one of the most intensively
      studied research areas of modern biology. Almost every aspect of life is
      intimately enmeshed with the proper regulation of cell death, which either
      contributes to or forms the basis of most human disease pathogenesis. Now, with
      our ever-expanding knowledge of the various death pathways, comes the hope that
      we might harness cell death--by either inhibition or promotion--to translate the
      concepts into cure.

PMID- 18082601
TI  - Variability and robustness in biomolecular systems.
AB  - The need to perform sophisticated information processing in an environment that
      is variable and noisy restricts the functional design of biological networks. We
      discuss several of the strategies that cells and multicellular organisms have
      evolved to deal with this demand.

PMID- 18082602
TI  - Coordinated control of dCTCF and gypsy chromatin insulators in Drosophila.
AB  - CTCF plays a central role in vertebrate insulators and forms part of the Fab-8
      insulator in Drosophila. dCTCF is present at hundreds of sites in the Drosophila
      genome, where it is located at the boundaries between bands and interbands in
      polytene chromosomes. dCTCF colocalizes with CP190, which is required for proper
      binding of dCTCF to chromatin, but not with the other gypsy insulator proteins
      Su(Hw) or Mod(mdg4)2.2. Mutations in the CP190 gene affect Fab-8 insulator
      activity, suggesting that CP190 is an essential component of both gypsy and dCTCF
      insulators. dCTCF is present at specific nuclear locations, forming large
      insulator bodies that overlap with those formed by Su(Hw), Mod(mdg4)2.2, and
      CP190. The results suggest that Su(Hw) and dCTCF may be the DNA-binding
      components of two different subsets of insulators that share CP190 and cooperate
      in the formation of insulator bodies to regulate the organization of the
      chromatin fiber in the nucleus.

PMID- 18082603
TI  - Purification of human telomerase complexes identifies factors involved in
      telomerase biogenesis and telomere length regulation.
AB  - The identities and roles of proteins associated with human telomerase remain
      poorly defined. To gain insight, we undertook an affinity purification of
      endogenously assembled human telomerase complexes. We show that specific subsets
      of H/ACA, Sm, and hnRNP proteins associate with active and inactive telomerase
      RNPs, while two NTPase proteins associate preferentially with active enzyme. All
      three core H/ACA-motif binding proteins are telomerase holoenzyme components
      essential for RNP accumulation. On the other hand, telomerase RNPs lacking
      interaction with Sm proteins or hnRNP C remain fully functional for telomere
      elongation. Curiously, overexpression of either associated hnRNP protein (hnRNP C
      and hnRNP U) or either NTPase protein (NAT10 and GNL3L) induced telomere
      shortening. Our findings suggest that endogenous human telomerase complexes are
      more heterogeneous than those of single-celled eukaryotes, have predominantly
      shared rather than telomerase-specific proteins, and make numerous regulatory
      interactions.

PMID- 18082604
TI  - A UAF1-containing multisubunit protein complex regulates the Fanconi anemia
      pathway.
AB  - The deubiquitinating enzyme USP1 controls the cellular levels of the DNA damage
      response protein Ub-FANCD2, a key protein of the Fanconi anemia DNA repair
      pathway. Here we report the purification of a USP1 multisubunit protein complex
      from HeLa cells containing stoichiometric amounts of a WD40 repeat-containing
      protein, USP1 associated factor 1 (UAF1). In vitro reconstitution of USP1
      deubiquitinating enzyme activity, using either ubiquitin-7-amido-4-methylcoumarin
      (Ub-AMC) or purified monoubiquitinated FANCD2 protein as substrates, demonstrates
      that UAF1 functions as an activator of USP1. UAF1 binding increases the catalytic
      turnover (kcat) but does not increase the affinity of the USP1 enzyme for the
      substrate (KM). Moreover, we show that DNA damage results in an immediate shutoff
      of transcription of the USP1 gene, leading to a rapid decline in the USP1/UAF1
      protein complex. Taken together, our results describe a mechanism of regulation
      of the deubiquitinating enzyme, USP1, and of DNA repair.

PMID- 18082605
TI  - Deubiquitination of FANCD2 is required for DNA crosslink repair.
AB  - Monoubiquitination of FANCD2 and PCNA promotes DNA repair. It causes chromatin
      accumulation of FANCD2 and facilitates PCNA's recruitment of translesion
      polymerases to stalled replication. USP1, a protease that removes monoubiquitin
      from FANCD2 and PCNA, was thought to reverse the DNA damage response of these
      substrates. We disrupted USP1 in chicken cells to dissect its role in a stable
      genetic system. USP1 ablation increases FANCD2 and PCNA monoubiquitination but
      unexpectedly results in DNA crosslinker sensitivity. This defective DNA repair is
      associated with constitutively chromatin-bound, monoubiquitinated FANCD2. In
      contrast, persistent PCNA monoubiquitination has negligible impact on DNA repair
      or mutagenesis. USP1 was previously shown to autocleave after DNA damage. In
      DT40, USP1 autocleavage is not stimulated by DNA damage, and expressing a
      noncleavable mutant in the USP1 knockout strain partially rescues crosslinker
      sensitivity. We conclude that efficient DNA crosslink repair requires FANCD2
      deubiquitination, whereas FANCD2 monoubiquitination is not dependent on USP1
      autocleavage.

PMID- 18082606
TI  - A positive role for NLI/Ldb1 in long-range beta-globin locus control region
      function.
AB  - Long-range interactions between distant regulatory elements, such as enhancers,
      and their target genes underlie the specificity of gene expression in many
      developmentally regulated gene families. NLI/Ldb1, a widely expressed nuclear
      factor, is a potential mediator of long-range interactions. Here, we show that
      NLI/Ldb1 and erythroid-binding partners GATA-1/SCL/LMO2 bind in vivo to the beta
      globin locus control region (LCR). The C-terminal LIM interaction domain of NLI
      is required for formation of the complex on chromatin. Loss of the LIM domain
      converts NLI into a dominant-negative inhibitor of globin gene expression, and
      knockdown of NLI by using shRNA results in failure to activate beta-globin
      expression. Kinetic studies reveal that the NLI/GATA-1/SCL/LMO2 complex is
      detected at the beta-globin promoter coincident with RNA Pol II recruitment, beta
      globin transcription, and chromatin loop formation during erythroid
      differentiation, providing evidence that NLI facilitates long-range gene
      activation.

PMID- 18082607
TI  - PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an
      adjacent bromodomain required for gene silencing.
AB  - Tandem PHD and bromodomains are often found in chromatin-associated proteins and
      have been shown to cooperate in gene silencing. Each domain can bind specifically
      modified histones: the mechanisms of cooperation between these domains are
      unknown. We show that the PHD domain of the KAP1 corepressor functions as an
      intramolecular E3 ligase for sumoylation of the adjacent bromodomain. The RING
      finger-like structure of the PHD domain is required for both Ubc9 binding and
      sumoylation and directs modification to specific lysine residues in the
      bromodomain. Sumoylation is required for KAP1-mediated gene silencing and
      functions by directly recruiting the SETDB1 histone methyltransferase and the
      CHD3/Mi2 component of the NuRD complex via SUMO-interacting motifs. Sumoylated
      KAP1 stimulates the histone methyltransferase activity of SETDB1. These data
      provide a mechanistic explanation for the cooperation of PHD and bromodomains in
      gene regulation and describe a function of the PHD domain as an intramolecular E3
      SUMO ligase.

PMID- 18082608
TI  - Competition between the ATPase Prp5 and branch region-U2 snRNA pairing modulates
      the fidelity of spliceosome assembly.
AB  - ATPase-facilitated steps during spliceosome function have been postulated to
      afford opportunities for kinetic proofreading. Spliceosome assembly requires the
      ATPase Prp5p, whose activity might thus impact fidelity during initial intron
      recognition. Using alanine mutations in S. cerevisiae Prp5p, we identified a
      suboptimal intron whose splicing could be improved by altered Prp5p activity and
      then, using this intron, screened for potent prp5 mutants. These prp5 alleles
      specifically alter branch region selectivity, with improved splicing in vivo of
      suboptimal substrates correlating with reduced ATPase activity in vitro for a
      series of mutants in ATPase motif III (SAT). Because these effects are abrogated
      by compensatory U2 snRNA mutations or other changes that increase branch region
      U2 pairing, these results explicitly link a fidelity event with a defined
      physical structure, the branch region-U2 snRNA duplex, and provide strong
      evidence that progression of the splicing pathway requires branch region-U2 snRNA
      pairing prior to Prp5p-facilitated conformational change.

PMID- 18082609
TI  - The DEAD-box protein Dbp5 controls mRNA export by triggering specific RNA:protein
      remodeling events.
AB  - Messenger RNA (mRNA) export involves the unidirectional passage of
      ribonucleoprotein particles (RNPs) through nuclear pore complexes (NPCs),
      presumably driven by the ATP-dependent activity of the DEAD-box protein Dbp5.
      Here we report that Dbp5 functions as an RNP remodeling protein to displace the
      RNA-binding protein Nab2 from RNA. Strikingly, the ADP-bound form of Dbp5 and not
      ATP hydrolysis is required for RNP remodeling. In vivo studies with nab2 and dbp5
      mutants show that a Nab2-bound mRNP is a physiological Dbp5 target. We propose
      that Dbp5 functions as a nucleotide-dependent switch to control mRNA export
      efficiency and release the mRNP from the NPC.

PMID- 18082610
TI  - Trm9-catalyzed tRNA modifications link translation to the DNA damage response.
AB  - Transcriptional and posttranslational signals are known mechanisms that promote
      efficient responses to DNA damage. We have identified Saccharomyces cerevisiae
      tRNA methyltransferase 9 (Trm9) as an enzyme that prevents cell death via
      translational enhancement of DNA damage response proteins. Trm9 methylates the
      uridine wobble base of tRNAARG(UCU) and tRNAGLU(UUC). We used computational and
      molecular approaches to predict that Trm9 enhances the translation of some
      transcripts overrepresented with specific arginine and glutamic acid codons. We
      found that translation elongation factor 3 (YEF3) and the ribonucleotide
      reductase (RNR1 and RNR3) large subunits are overrepresented with specific
      arginine and glutamic acid codons, and we demonstrated that Trm9 significantly
      enhances Yef3, Rnr1, and Rnr3 protein levels. Additionally, we identified 425
      genes, which included YEF3, RNR1, and RNR3, with a unique codon usage pattern
      linked to Trm9. We propose that Trm9-specific tRNA modifications enhance codon
      specific translation elongation and promote increased levels of key damage
      response proteins.

PMID- 18082612
TI  - PDZ domains of Par-3 as potential phosphoinositide signaling integrators.
AB  - Multiple PDZ domain scaffold protein Par-3 and phosphoinositides (PIPs) are
      required for polarity in diverse cell types. We show that the second PDZ domain
      of Par-3 binds to phosphatidylinositol (PI) lipid membranes with high affinity.
      We further demonstrate that a large subset of PDZ domains in mammalian genomes
      are capable of binding to PI lipid membranes, indicating that lipid binding is
      the second most prevalent interaction mode of PDZ domains known to date. The
      biochemical and structural basis of Par-3 PDZ2-mediated membrane interaction is
      characterized in detail. The membrane binding capacity of Par-3 PDZ2 is critical
      for epithelial cell polarization. Interestingly, the lipid phosphatase PTEN
      directly binds to the third PDZ domain of Par-3. The concatenation of the PIP
      binding PDZ2 and the lipid phosphatase PTEN-binding PDZ3 endows Par-3 as an ideal
      scaffold protein for integrating PIP signaling events during cellular
      polarization.

PMID- 18082613
TI  - c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1.
AB  - c-IAP1, a member of the inhibitor of apoptosis protein (IAP) family and a RING
      finger ubiquitin ligase (E3), has been proposed to be an important oncogene. In
      many types of cancers, the levels of c-IAP1 are upregulated, which contributes
      positively to tumorigenesis. However, the mechanism by which c-IAP1 promotes
      tumorigenesis has proven elusive. Although proteins in the IAP family may
      function as caspase inhibitors, c-IAP1 was shown to be a poor inhibitor of
      caspases. Here we show that c-IAP1 catalyzes ubiquitination of Max-dimerization
      protein-1 (Mad1), a cellular antagonist of Myc. Ubiquitination of Mad1 by c-IAP1
      accelerates its degradation by the 26S proteasome pathway, and this reduction of
      the Mad1 levels cooperates with Myc to promote cell proliferation. Our results
      demonstrate that c-IAP1 exerts its oncogenic functions by promoting the
      degradation of an important negative regulator in the Myc pathway.

PMID- 18082611
TI  - Structural organization of the anaphase-promoting complex bound to the mitotic
      activator Slp1.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is a conserved multisubunit E3
      ubiquitin (Ub) ligase required to signal the degradation of key cell-cycle
      regulators. Using single particle cryo-electron microscopy (cryo-EM), we have
      determined a three-dimensional (3D) structure of the core APC/C from
      Schizosaccharomyces pombe bound to the APC/C activator Slp1/Cdc20. At the 27 A
      resolution of our density map, the APC/C is a triangular-shaped structure,
      approximately 19x17x15 nm in size, with a deep internal cavity and a prominent
      horn-like protrusion emanating from a lip of the cavity. Using antibody labeling
      and mutant analysis, we have localized 12 of 13 core APC/C components, as well as
      the position of the activator Slp1, enabling us to propose a structural model of
      APC/C organization. Comparison of the APC/C with another multiprotein E3 ligase,
      the SCF complex, uncovers remarkable structural similarities.

PMID- 18082615
TI  - A peptide affinity column for the identification of integrin alpha IIb-binding
      proteins.
AB  - To understand the regulation of integrin alpha(IIb)beta(3), a critical platelet
      adhesion molecule, we have developed a peptide affinity chromatography method
      using the known integrin regulatory motif, LAMWKVGFFKR. Using standard Fmoc
      chemistry, this peptide was synthesized onto a Toyopearl AF-Amino-650 M resin on
      a 6-aminohexanoic acid (Ahx) linker. Peptide density was controlled by
      acetylation of 83% of the Ahx amino groups. Four recombinant human proteins
      (CIB1, PP1, ICln and RN181), previously identified as binding to this integrin
      regulatory motif, were specifically retained by the column containing the
      integrin peptide but not by a column presenting an irrelevant peptide.
      Hemoglobin, creatine kinase, bovine serum albumin, fibrinogen and alpha-tubulin
      failed to bind under the chosen conditions. Immunodetection methods confirmed the
      binding of endogenous platelet proteins, including CIB1, PP1, ICln RN181, AUP-1
      and beta3-integrin, from a detergent-free platelet lysate. Thus, we describe a
      reproducible method that facilitates the reliable extraction of specific integrin
      binding proteins from complex biological matrices. This methodology may enable
      the sensitive and specific identification of proteins that interact with linear,
      membrane-proximal peptide motifs such as the integrin regulatory motif
      LAMWKVGFFKR.

PMID- 18082614
TI  - Construction of a reagentless glucose biosensor using molecular exciton
      luminescence.
AB  - Fluorescent protein biosensors, which exhibit a significant change in
      fluorescence based on the physical interaction between protein and ligand, may
      prove to be effective tools to measure a variety of analytes. In particular, real
      time monitoring of glucose levels has potential applications in bioprocess
      monitoring and in minimizing health complications caused by diabetes. In this
      work, site-directed mutagenesis of the Escherichia coli glucose/galactose binding
      protein (GGBP) was used to engineer double-cysteine mutations that allowed
      selective covalent attachment of thiol-reactive dyes. Because GGBP undergoes a
      large conformational change on the addition of glucose, rational placement of
      these sites allowed glucose-dependent spatial realignment of the two
      fluorophores, which was monitored as a change in fluorescence intensity and
      extinction coefficients. Using targeted mutagenesis of the GGBP binding pocket,
      glucose biosensors were created to measure concentrations spanning five orders of
      magnitude (0.04-12,000 microM). The glucose biosensor retained its function in
      complex solutions that contained realistic concentrations of protein and
      potential interfering agents found in blood serum. In addition to the development
      of a fluorescent protein sensor for glucose, this work helps to expand the
      spectroscopic tools used for the detection of conformational movements within a
      single polypeptide chain.

PMID- 18082616
TI  - Submitochondrial localization of associated mu-calpain and calpastatin.
AB  - Recently, we have reported the presence of calpain-calpastatin system in
      mitochondria of bovine pulmonary smooth muscle [P. Kar, T. Chakraborti, S. Roy,
      R. Choudhury, S. Chakraborti, Arch. Biochem. Biophys. 466 (2007) 290-299].
      Herein, we report its localization in the mitochondria. Immunoblot,
      immunoelectron microscopy and casein zymographic studies suggest that mu-calpain
      and calpastatin are present in the inner mitochondrial membrane; but not in the
      outer mitochondrial membrane or in the inter membrane space or in the matrix of
      the mitochondria. Co-immunoprecipitation studies suggest that mu-calpain
      calpastatin is associated in the inner mitochondrial membrane. Additionally, the
      proteinase K and sodium carbonate treatments of the mitoplasts revealed that mu
      calpain is integrally and calpastatin is peripherally embedded to the outer
      surface of inner mitochondrial membrane. These studies indicate that an
      association between mu-calpain and calpastatin occurs in the inner membrane
      towards the inter membrane space of the mitochondria, which provides better
      insight about the protease regulation towards initiation of apoptotic processes
      mediated by mitochondria.

PMID- 18082617
TI  - In vivo effect of an antilipolytic drug (3,5'-dimethylpyrazole) on autophagic
      proteolysis and autophagy-related gene expression in rat liver.
AB  - Autophagy is an intracellular pathway induced by starvation, inhibited by
      nutrients, that is responsible for degradation of long-lived proteins and altered
      cell organelles. This process is involved in cell maintenance could be induced by
      antilipolytic drugs and may have anti-aging effects [A. Donati, The involvement
      of macroautophagy in aging and anti-aging interventions, Mol. Aspects Med. 27
      (2006) 455-470]. We analyzed the effect of an intraperitoneal injection of an
      antilipolytic agent (3,5'-dimethylpyrazole, DMP, 12mg/kg b.w.), that mimics
      nutrient shortage on autophagy and expression of autophagic genes in the liver of
      male 3-month-old Sprague-Dawley albino rats. Autophagy was evaluated by observing
      electron micrographs of the liver autophagosomal compartment and by monitoring
      protein degradation assessed by the release of valine into the bloodstream. LC3
      gene expression, whose product is one of the best known markers of autophagy, was
      also monitored. As expected, DMP decreased the plasma levels of free fatty acids,
      glucose, and insulin and increased autophagic vacuoles and proteolysis. DMP
      treatment caused an increase in the expression of the LC3 gene although this
      occurred later than the induction of authophagic proteolysis caused by DMP.
      Glucose treatment rescued the effects caused by DMP on glucose and insulin plasma
      levels and negatively affected the rate of autophagic proteolysis, but did not
      suppress the positive regulatory effect on LC3 mRNA levels. In conclusion,
      antilipolytic drugs may induce both autophagic proteolysis and higher expression
      of an autophagy-related gene and the effect on autophagy gene expression might
      not be secondary to the stimulation of autophagic proteolysis.

PMID- 18082619
TI  - Clusterin, a novel modulator of TGF-beta signaling, is involved in Smad2/3
      stability.
AB  - Clusterin (CLU) is known as a multifunctional protein involved in a variety of
      physiological processes including lipid transport, epithelial cell
      differentiation, tumorigenesis, and apoptosis. It is known that CLU interacts
      with TGF-beta type ll receptor (TbetaRll). However, the relationship of CLU and
      TGF-beta signaling is unclear. Here we present that CLU is a novel modulator of
      TGF-beta signaling by regulating Smad2/3 proteins. Overexpression of CLU enhanced
      TGF-beta-induced transcriptional activity and increased the amount of Smad2/3
      proteins, while CLU siRNA repressed TGF-beta-induced transcriptional activity and
      decreased the amount of Smad2/3 proteins in Hep3B cells. We also found that CLU
      was involved in Smad2/3 stability at the protein level. These findings suggest
      that CLU regulates TGF-beta signaling pathway by modulating the stability of
      Smad2/3 proteins.

PMID- 18082618
TI  - CD437 induces apoptosis in ovarian adenocarcinoma cells via ER stress signaling.
AB  - A synthetic retinoid, CD437, has been shown to exert potent anti-tumor activity
      against various types of cancer cell lines, regardless of their sensitivities to
      natural retinoids. We herein demonstrate that CD437 induces endoplasmic reticulum
      (ER) stress, including the up-regulation of CHOP, BIP and GADD34 mRNA through ER
      stress transducer (PERK and IRE1alpha) activation in an ovarian adenocarcinoma
      cell line, SKOV3. It was also shown that CD437 induced the CHOP and GADD34
      expressions in another four ovarian adenocarcinoma cell lines, indicating that
      CD437 functions as an ER stress inducer in these cell lines. Moreover, the siRNA
      mediated knockdown of inducible CHOP expression prevented the cytotoxic effect of
      CD437. These results suggest that ER stress plays an important role in the
      mechanism by which CD437 induces apoptosis in ovarian adenocarcinoma cells.

PMID- 18082620
TI  - Structural studies of the SET domain from RIZ1 tumor suppressor.
AB  - RIZ1 is a transcriptional regulator and tumor suppressor that catalyzes
      methylation of lysine 9 of histone H3. It contains a distinct SET domain,
      sometimes referred to as PR (PRDI-BF1 and RIZ1 homology) domain, that is
      responsible for its catalytic activity. We determined the solution structure of
      the PR domain from RIZ1 and characterized its interaction with S-adenosyl-l
      homocysteine (SAH) and a peptide from histone H3. Despite low sequence identity
      with canonical SET domains, the PR domain displays a typical SET fold including a
      pseudo-knot at the C-terminus. The N-flanking sequence of RIZ1 PR domain adopts a
      novel conformation and interacts closely with the SET fold. The C-flanking
      sequence contains an alpha-helix that points away from the protein face that
      harbors active site in other SET domains. The SET fold of RIZ1 does not have
      detectable affinity for SAH but it interacts with a synthetic peptide comprising
      residues 1-20 of histone H3.

PMID- 18082621
TI  - Mechano-sensitive channels regulate the stomatal aperture in Vicia faba.
AB  - In the bright fields, stomata of the plants are fully opened to raise the
      transpiration rate and CO(2) uptake required for photosynthesis. Stomatal opening
      is driven by the activation of plasma membrane H(+)-ATPase and K(+)(in) channels,
      and the Ca(2+)-dependent inactivation and blockage of both components were
      supposed to be inevitable function to regulate the stomatal aperture. Although,
      it is still obscure how these activities are regulated at the open state.
      Application of an amphipathic membrane creator, trinitrophenol (TNP), instantly
      generates the convex curvature in the plasma membrane, which occurs in the phases
      of stomatal opening and closure. TNP surely activates mechanosensitive Ca(2+)
      permeable channels and attenuates the promotion of stomatal opening, but does not
      inhibit and promote stomatal closure. These results suggest that activation of
      mechanosensitive Ca(2+)-permeable channels regulates the opening phase of stomata
      in plants.

PMID- 18082622
TI  - Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of
      oxidative CPT I modification.
AB  - Intracellular redox balance may affect nutrient metabolism in skeletal muscle.
      Astaxanthin, a carotenoid contained in various natural foods, exerts high
      antioxidative capacity in the skeletal muscles. The present study investigated
      the effect of astaxanthin on muscle lipid metabolism in exercise. ICR mice (8
      weeks old) were divided into four different groups: sedentary, sedentary treated
      with astaxanthin, running exercise, and exercise treated with astaxanthin. After
      4 weeks of treatment, exercise groups performed treadmill running. Astaxanthin
      increased fat utilization during exercise compared with mice on a normal diet
      with prolongation of the running time to exhaustion. Colocalization of fatty acid
      translocase with carnitine palmitoyltransferase I (CPT I) in skeletal muscle was
      increased by astaxanthin. We also found that hexanoyl-lysine modification of CPT
      I was increased by exercise, while astaxanthin prevented this increase. In
      additional experiment, we found that astaxanthin treatment accelerated the
      decrease of body fat accumulation with exercise training. Our results suggested
      that astaxanthin promoted lipid metabolism rather than glucose utilization during
      exercise via CPT I activation, which led to improvement of endurance and
      efficient reduction of adipose tissue with training.

PMID- 18082623
TI  - Isolation of inhibitory RNA aptamers against severe acute respiratory syndrome
      (SARS) coronavirus NTPase/Helicase.
AB  - Recent outbreak of Severe Acute Respiratory Syndrome (SARS) that caused almost
      800 victims requires a development of efficient inhibitor against SARS
      coronavirus (SCV). In this study, RNA aptamers against SCV NTPase/Helicase
      (nsP10) were isolated from RNA library containing random sequences of 40 nts
      using in vitro selection technique. Nucleotide sequences of enriched RNA aptamer
      pool (ES15 RNA) contain AG-rich conserved sequence of 10-11 nucleotides
      [AAAGGR(G)GAAG; R, purine base] and/or additional sequence of 5 nucleotides
      [GAAAG], which mainly reside at the loop region in all the predicted secondary
      structures. Isolated RNAs were observed to efficiently inhibit double-stranded
      DNA unwinding activity of the helicase by up to approximately 85% with an IC(50)
      value of 1.2nM but show a slight effect on ATPase activity of the protein in the
      presence of cofactor, poly (rU). These results suggest that the pool of selected
      aptamers might be potentially useful as anti-SCV agents.

PMID- 18082625
TI  - Structure, dynamics, and stability of assemblies of the human prion fragment
      SNQNNF.
AB  - Misfolding of the prion protein (PrP) is associated with the development of
      Transmissible Spongiform Encephalopathies. The recent crystal structure of
      'steric zipper' aggregates of the peptide SNQNNF (human PrP fragment 170-175) has
      highlighted its potential involvement in the misfolding process. A detailed
      molecular dynamics investigation on SNQNNF aggregates has been performed to
      analyze the behavior of the assemblies in a non-crystalline context. Stability,
      dynamics, and structural features suggest that SNQNNF assemblies are very good
      candidates to be involved in the structure of PrP fibrils. In addition, the
      analysis of small aggregates shows that steric zipper interfaces are able to
      stabilize assemblies composed of four strands per sheet. Altogether, the present
      findings indicate that steric zipper may play a key role in prion diseases. This
      suggestion is also corroborated by MD analyses of point mutations within the
      region 170-175.

PMID- 18082624
TI  - 0610009K11Rik, a testis-specific and germ cell nuclear receptor-interacting
      protein.
AB  - Using an in silico approach, a putative nuclear receptor-interacting protein
      0610009K11Rik was identified in mouse testis. We named this gene testis-specific
      nuclear receptor-interacting protein-1 (Tnrip-1). Tnrip-1 was predominantly
      expressed in the testis of adult mouse tissues. Expression of Tnrip-1 in the
      testis was regulated during postnatal development, with robust expression in 14
      day-old or older testes. In situ hybridization analyses showed that Tnrip-1 is
      highly expressed in pachytene spermatocytes and spermatids. Consistent with its
      mRNA expression, Tnrip-1 protein was detected in adult mouse testes.
      Immunohistochemical studies showed that Tnrip-1 is a nuclear protein and mainly
      expressed in pachytene spermatocytes and round spermatids. Moreover, co
      immunoprecipitation analyses showed that endogenous Tnrip-1 protein can interact
      with germ cell nuclear receptor (GCNF) in adult mouse testes. Our results suggest
      that Tnrip-1 is a testis-specific and GCNF-interacting protein which may be
      involved in the modulation of GCNF-mediated gene transcription in spermatogenic
      cells within the testis.

PMID- 18082626
TI  - Dihydroorotase of human malarial parasite Plasmodium falciparum differs from host
      enzyme.
AB  - Plasmodium falciparum, the causative agent of human malaria, is totally dependent
      on de novo pyrimidine biosynthetic pathway. A gene encoding P. falciparum
      dihydroorotase (pfDHOase) was cloned and expressed in Escherichia coli as
      monofunctional enzyme. PfDHOase revealed a molecular mass of 42kDa. In gel
      filtration chromatography, the major enzyme activity eluted at 40kDa, indicating
      that it functions in a monomeric form. This was similarly observed using the
      native enzyme purified from P. falciparum. Interestingly, kinetic parameters of
      the enzyme and inhibitory effect by orotate and its 5-substituted derivatives
      parallel that found in mammalian type I DHOase. Thus, the malarial enzyme shares
      characteristics of both type I and type II DHOases. This study provides the
      monofunctional property of the parasite DHOase lending further insights into its
      differences from the human enzyme which forms part of a multifunctional protein.

PMID- 18082627
TI  - SP600125 inhibits Kv channels through a JNK-independent pathway in cancer cells.
AB  - Kv channels represent new important targets for the control of cancer growth and
      a better understanding of their regulating pathways in cancer cells is necessary
      to develop therapeutic strategies. In this study, we have addressed the putative
      modulation of Kv by MAP kinases through a pharmacological approach. We have found
      that the commonly used JNK inhibitor SP600125 strongly inhibits Kv channels
      through a JNK-independent pathway, likely interacting directly with the channels
      at the external side of the membrane. Our results indicate that the use of this
      compound may produce misleading conclusions for the role of JNK in cell cycle.

PMID- 18082628
TI  - Expression of BCR-ABL1 oncogene relative to ABL1 gene changes overtime in chronic
      myeloid leukemia.
AB  - Using a quantitative single nucleotide polymorphism (SNP) assay we have
      investigated the changes in the expression of the BCR-ABL1 oncogene relative to
      the wild-type ABL1 and BCR alleles in cells from chronic myeloid leukemia (CML)
      patients not responding to therapy. The results show a progressive increase in
      the BCR-ABL1 oncogene expression at the expense of decreased expression of the
      ABL1 allele, not involved in the fusion. No relative changes in the expression of
      the two BCR alleles were found. These results demonstrate that allele-specific
      changes in gene expression, with selective, progressive silencing of the wild
      type ABL1 allele in favor of the oncogenic BCR-ABL1 allele occur in CML patients
      with therapy-resistant disease.

PMID- 18082629
TI  - Fragments of obestatin as modulators of feed intake, circulating lipids, and
      stored fat.
AB  - Obestatin, shown to reduce feed intake and gain in body weight in rodents, is a
      very attractive candidate to be used against obesity. In this study, we aimed to
      investigate the relationship between the primary structure and activity of
      obestatin. Also of interest to us is a peptide of minimal length that closely
      mimics obestatin. Towards the same, we synthesized rodent obestatin and three
      overlapping fragments spanning residues 1-13, 6-18, and 11-23 of obestatin. These
      peptides subsequent to purification and characterization were tested upon adult
      male mice for their ability to reduce feed intake and gain in body weight. The N
      terminal peptide (residues 1-13) mimicked obestatin the closest. The middle
      fragment (residues 6-18) significantly reduced epididymal fat without much
      altering feed intake or body weight.

PMID- 18082630
TI  - Lower hemoglobin concentrations and subsequent decline in kidney function in an
      apparently healthy population aged 60 year and older.
AB  - BACKGROUND: Anemia and decreased kidney function are recognized as risk factors
      for morbidity and mortality in the elderly. The role of hemoglobin in renal
      function changes among elderly patients is not fully understood. METHODS: Of
      1,500 people screened, 121 normotensive non-diabetic elderly patients were
      recruited, and underwent biochemistry examinations at the baseline, second and
      fourth years of a 4-year longitudinal study. Serum creatinine and calculated
      renal parameters, including the Cockroft-Gault (CG) formula, Modification of Diet
      in Renal Disease (MDRD) Study and abbreviated MDRD (abMDRD) equations were used
      to evaluate renal function and progression of kidney disease. Chronic kidney
      disease (CKD) was defined as a glomerular filtration rate (GFR) of <60
      ml/min/1.73 m(2). Multivariate regression analyses were used to explore
      predictors for decline in renal parameters. RESULTS: Ages ranged from 60 to 81
      year (mean: 71.8+/-3.8). Baseline hemoglobin concentrations ranged from 11.9 to
      17.3 g/dl (mean: 14.1+/-1.1). Serum creatinine increased and CG creatinine
      clearance (CrCl), MDRD and abMDRD GFR decreased during follow-up (all p< or
      =0.001). The prevalence of CKD significantly increased only in those with
      baseline hemoglobin concentrations of <14 g/dl (p< or =0.03, based on findings of
      both MDRD and abMDRD GFR). Baseline hemoglobin correlates with 4-year changes of
      MDRD and abMDRD GFR in univariate (both p<0.001) and multivariate regression
      analyses (both p<0.05). CONCLUSIONS: This longitudinal study revealed that the
      aging process was associated with decline of renal function in the elderly.
      Because hemoglobin concentrations are an independent predictor for subsequent
      decline in kidney function, it should be considered in the assessment of renal
      disease and GFR in the elderly.

PMID- 18082631
TI  - Undetectable phenytoin serum levels by an automated particle-enhanced
      turbidimetric inhibition immunoassay in a patient with monoclonal IgM lambda.
AB  - INTRODUCTION: Phenytoin is a drug used for the treatment of different types of
      seizures. Its variable pharmacokinetics, mainly a consequence of variable
      bioavailability, saturable protein binding and saturable hepatic metabolism,
      predisposes the drug to therapeutic drug monitoring. Several methods to analyze
      the drug in serum exist with immunoassays being the method of choice for routine
      measurements. Immunoassays are specific and sensitive, but cross-reactivity,
      possibly leading to erroneous serum levels, is a concern. We report a patient
      with falsely undetectable phenytoin serum levels. CASE REPORT: This 73-year old
      woman was treated with intravenous phenytoin due to epilepsia partialis continua
      in the context of a bilateral cerebrovascular insult. Anamnestically, a chronic
      lymphatic leukemia was known. In this patient, serum phenytoin levels became only
      detectable by the particle enhanced turbidimetric inhibition immunoassay used
      after precipitation of serum proteins. Protein electrophoresis revealed a
      monoclonal immunoglobulin, identified as IgMlambda. With other methods such as
      HPLC and fluorescence depolarization immunoassay, phenytoin was detectable.
      CONCLUSION: We propose interference between the monoclonal IgMlambda and/or other
      serum proteins and the particle-enhanced turbidimetric inhibition immunoassay,
      rendering phenytoin falsely undetectable in samples of this patient. In such
      patients, alternative methods such as HPLC should be used to prevent dosage
      errors.

PMID- 18082632
TI  - Influence of age and visceral fat area on plasma adiponectin concentrations in
      women with normal glucose tolerance.
AB  - BACKGROUND: Age-related adiponectin concentration has been discrepantly reported.
      We investigated the distribution of adiponectin by age in healthy women with
      normal glucose tolerance (NGT) and the relationship of adiponectin with visceral
      fat area (VFA). METHODS: Three-hundred fifty-nine women (age: 38+/-0.6 years,
      BMI: 26.5+/-0.2 kg/m(2)) were categorized into 4 age-groups: 20-29, 30-39, 40-49,
      and 50-64 years. Computed tomography was performed to measure abdominal fat area
      and adiponectin, TNF-alpha, interleukin-6 (IL-6), CRP, insulin, free fatty acid
      (FFA), and blood urea nitrogen (BUN) were determined. RESULTS: No significant
      differences were observed in BMI, total body fat percent and concentrations of
      insulin, IL-6 and CRP among age-groups. Waist circumference, total fat area at
      L4, and FFA were significantly higher only in postmenopausal women than in
      previous decades of premenopausal women. VFA, adiponectin and TNF-alpha
      concentrations are significantly higher in older women than in younger women.
      Higher adiponectin concentration in older women was clearly shown even after
      adjustment for VFA (P<0.05). Age per se was positively correlated with plasma
      adiponectin concentrations (r=0.21, P<0.001) and these relationship became
      stronger (r=0.36, P<0.001) after controlled for VFA. VFA was negatively
      correlated with adiponectin (r=-0.16, P<0.01) in total studied population.
      However, when analyzed subgroups separately, a strong negative correlation (r=
      0.37, P<0.001) was found in younger women (<40 years), while a weak significant
      relationship (r=-0.18, P<0.05) was found in older women (> or =40 years). In a
      multiple stepwise regression model to predict adiponectin, only age and VFA
      remained in the model at P<0.001. CONCLUSIONS: We observed a significant positive
      relationship between plasma adiponectin and age, even after adjustment for
      visceral adiposity. These associations suggest that adiponectin concentrations
      are affected by visceral adiposity, with additional independent effects of age.

PMID- 18082634
TI  - Structure and mechanisms of the DsbB-DsbA disulfide bond generation machine.
AB  - All organisms possess specific cellular machinery that introduces disulfide bonds
      into proteins newly synthesized and transported out of the cytosol. In E. coli,
      the membrane-integrated DsbB protein cooperates with ubiquinone to generate a
      disulfide bond, which is transferred to DsbA, a periplasmic dithiol oxido
      reductase that serves as the direct disulfide bond donor to proteins folding
      oxidatively in this compartment. Despite the extensive accumulation of knowledge
      on this oxidation system, molecular details of the DsbB reaction mechanisms had
      been controversial due partly to the lack of structural information until our
      recent determination of the crystal structure of a DsbA-DsbB-ubiquinone complex.
      In this review we discuss the structural and chemical nature of reaction
      intermediates in the DsbB catalysis and the illuminated molecular mechanisms that
      account for the de novo formation of a disulfide bond and its donation to DsbA.
      It is suggested that DsbB gains the ability to oxidize its specific substrate,
      DsbA, having very high redox potential, by undergoing a DsbA-induced
      rearrangement of cysteine residues. One of the DsbB cysteines that are now
      reduced then interacts with ubiquinone to form a charge transfer complex, leading
      to the regeneration of a disulfide at the DsbB active site, and the cycle can
      begin anew.

PMID- 18082635
TI  - Identification, cloning and functional characterization of a novel dermonecrotic
      toxin (phospholipase D) from brown spider (Loxosceles intermedia) venom.
AB  - Brown spider bites are associated with lesions including dermonecrosis,
      gravitational spreading and a massive inflammatory response, along with systemic
      problems that may include hematological disturbances and renal failure. The
      mechanisms by which the venom exerts its noxious effects are currently under
      investigation. It is known that the venom contains a major toxin (dermonecrotic
      toxin, biochemically a phospholipase D) that can experimentally induce
      dermonecrosis, inflammatory response, animal mortality and platelet aggregation.
      Herein, we describe cloning, heterologous expression, purification and
      functionality of a novel isoform of the 33 kDa dermonecrotic toxin. Circular
      dichroism analysis evidenced correct folding for the toxin. The recombinant toxin
      was recognized by whole venom serum antibodies and by a specific antibody to a
      previously described dermonecrotic toxin. The identified toxin was found to
      display phospholipase activity and dermonecrotic properties. Additionally, the
      toxin caused a massive inflammatory response in rabbit skin dermis, evoked
      platelet aggregation, increased vascular permeability, caused edema and death in
      mice. These characteristics in combination with functional studies for other
      dermonecrotic toxins illustrate that a family of dermonecrotic toxins exists, and
      includes a novel member with high activity that may be useful for future
      structural and functional studies.

PMID- 18082636
TI  - N-acetylcysteine amide (AD4) attenuates oxidative stress in beta-thalassemia
      blood cells.
AB  - Many aspects of the pathology in beta-hemoglobinopathies (beta-thalassemia and
      sickle cell anemia) are mediated by oxidative stress. In the present study we
      tested a novel thiol compound, N-acetylcysteine amide (AD4), the amide form of N
      acetyl cysteine (NAC) for its antioxidant effects. Using flow-cytometry, we
      showed that in vitro treatment of blood cells from beta-thalassemic patients with
      AD4 elevated the reduced glutathione (GSH) content of red blood cells (RBC),
      platelets and polymorphonuclear (PMN) leukocytes, and reduced their ROS. These
      effects resulted in a significant reduced sensitivity of thalassemic RBC to
      hemolysis and phagocytosis by macrophages. Intra-peritoneal injection of AD4 to
      beta-thalassemic mice (150 mg/kg) reduced the parameters of oxidative stress
      (p<0.001). Our results show the superiority of AD4, compared to NAC, in reducing
      oxidative stress markers in thalassemic cells both in vitro and in vivo.

PMID- 18082637
TI  - Differential regulation of apolipoprotein A-I gene expression by vitamin D
      receptor modulators.
AB  - We have found that 1,25-dihydroxy-cholecalciferol (1,25-(OH)(2)D(3)) represses
      the expression of the apolipoprotein A-I (apo A-I) gene in hepatocytes. In this
      manuscript we examined the effects of the vitamin D receptor (VDR) modulators
      EB1089 (EB) and ZK191784 (ZK) on expression of the apo A-I gene in liver (HepG2)
      and in intestinal (Caco-2) cells. In HepG2 cells, EB and ZK induced apo A-I
      secretion and gene promoter activity in a dose-dependent manner. This induction
      did not require the VDR since antisense-mediated inhibition of VDR had no
      appreciable effect on apo A-I promoter activity in cells treated with EB or ZK.
      Although repression of apo A-I gene expression by 1,25-(OH)(2)D(3) in hepatocytes
      required nuclear receptor binding to site A in the promoter, this cis-element was
      insufficient for induction of apo-AI by EB and ZK. In Caco-2 cells, treatment
      with 1,25-(OH)(2)D(3) had no effect on apo A-I protein secretion or promoter
      activity while EB induced and ZK inhibited apo A-I gene expression. Gel shift
      assays showed that none of the treatments resulted in a change in site A binding
      activity. These results indicate that VDR modulators in hepatocytes and
      intestinal cells differentially regulate expression of the apo A-I gene.

PMID- 18082638
TI  - Reactive oxygen species are generated through a BLT2-linked cascade in Ras
      transformed cells.
AB  - Although production of reactive oxygen species (ROS) by oncogenic Ras is thought
      to be crucial for Ras transformation, very little is known about the signaling
      mechanism involved. In the present study, we investigated whether BLT2, a low
      affinity leukotriene B(4) receptor, is involved in the generation of ROS in H
      Ras(V12)-transformed fibroblasts. We show that downregulation of BLT2 using RNA
      interference or antisense oligonucleotides inhibits ROS generation, and that Nox1
      acts downstream of BLT2. Moreover, BLT2 overexpression caused increased ROS
      production and partial transformation. Taken together, our results suggest that a
      BLT2-Nox1-linked cascade is responsible for the elevated ROS generation in Ras
      transformed cells. Our finding may contribute to clarifying the signaling events
      underlying the enhanced levels of ROS frequently observed in various transformed
      cells and possibly serve as a basis for developing new therapeutic strategies for
      human cancers.

PMID- 18082639
TI  - trans-Arachidonic acids induce a heme oxygenase-dependent vasorelaxation of
      cerebral microvasculature.
AB  - Nitrative stress is an important regulator of vascular tone. We have recently
      described that trans-arachidonic acids (TAA) are major products of NO(2)(.)
      mediated isomerization of arachidonic acid in cell membranes and that nitrative
      stress increases TAA levels leading to neural microvascular degeneration. In the
      present study, we explored whether TAA exert acute effects on neuromicrovascular
      tone and investigated potential mechanisms thereof. TAA induced an endothelium
      dependent vasorelaxation of rat brain pial microvasculature. This vasorelaxation
      was independent of nitric oxide, prostanoids, lipoxygenase products, and CYP(450)
      metabolite trans-hydroxyeicosatetraenoic acids. However, inhibition of heme
      oxygenase (using zinc protoporphyrin IX) and of dependent soluble guanylate
      cyclase (sGC; using ODQ) significantly diminished (by approximately 70%) the TAA
      induced vasorelaxation. Consistent with these findings, TAA stimulated heme
      oxygenase (HO)-2-dependent bilirubin (using siRNA HO-2) and cGMP formation, and
      the HO product carbon monoxide (using CO-releasing CORM-2) reproduced the sGC
      dependent cGMP formation and vasorelaxation. Further exploration revealed that
      TAA-induced vasorelaxation and bilirubin formation (HO activation) were nearly
      abrogated by large-conductance calcium-dependent potassium channels (BK(Ca))
      (using TEA and iberiotoxin). Opening of BK(Ca) with the selective activator
      NS1619 induced a concentration-dependent vasorelaxation, which was inhibited by
      HO and sGC inhibitors. Coimmunoprecipitation suggested a molecular complex
      interaction between BK(Ca) and HO-2 (but not HO-1). Collectively, these findings
      identify new properties of TAA, specifically cerebral vasorelaxation through
      interactive activation of BK(Ca) with HO-2 and, in turn, sGC. Our findings
      provide new insights into the characterization of nitrative stress-derived TAA
      products, by showing they can act as acute mediators of nitrative stress on
      neurovascular tone.

PMID- 18082640
TI  - Treatment with a farnesyltransferase inhibitor improves survival in mice with a
      Hutchinson-Gilford progeria syndrome mutation.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a progeroid syndrome characterized
      by multiple aging-like disease phenotypes. We recently reported that a protein
      farnesyltransferase inhibitor (FTI) improved several disease phenotypes in mice
      with a HGPS mutation (Lmna(HG/+)). Here, we investigated the impact of an FTI on
      the survival of Lmna(HG/+) mice. The FTI significantly improved the survival of
      both male and female Lmna(HG/+) mice. Treatment with the FTI also improved body
      weight curves and reduced the number of spontaneous rib fractures. This study
      provides further evidence for a beneficial effect of an FTI in HGPS.

PMID- 18082641
TI  - A quantitative and morphometric study of tryptase-positive mast cells in
      cutaneous leprosy lesions.
AB  - While mast cells are known to induce differences in the matrix structures,
      microvascular patterns, and immune responses in a number of diseases, the
      possible role of mast cells in these same processes over the spectrum of leprosy
      has not yet been investigated. Thus, ascertaining the possible influence of mast
      cells in the outcome of the anti-leprosy response to Mycobacterium leprae is of
      major importance. In this study, 51 cutaneous biopsies of leprosy patients were
      stained with anti-tryptase antibody in order to quantify mast cells in leprosy
      lesions and compare the number and size of these cells in all the forms of
      leprosy. Biopsies were grouped according to an adapted Ridley-Jopling clinical
      immunological classification (17 T, 17 B and 17 L). It was found that the L
      (lepromatous leprosy) group had the lowest dermal mast cell density values among
      the three groups studied. Furthermore, the average mast cell cross-sectional area
      was significantly higher in the L in comparison to the B (borderline-borderline)
      and T (tuberculoid) biopsies, suggesting mast cell functional differences within
      the groups. The higher mast cell density in the T and B groups was considered
      indirect evidence of the role of mast cells in the activated immune response to
      M. leprae infection.

PMID- 18082642
TI  - [Placental glycoproteins in the mammals].
AB  - Placental tissue exhibits a typical glycosylation pattern, which differs from
      that observed in the pituitary gland. Depending to the species and pregnancy
      period, the placenta synthesizes diverse glycoproteins, some of which have
      significant hormonal activity, others being detected in maternal circulation.
      Thus, these molecules are of interest both from a fundamental and clinical point
      of view. Among the mammalian placental glycoproteins currently recognized,
      chorionic gonadotrophins from primates and Equidae, placental lactogen from
      bovines and the pregnancy-associated glycoproteins from ruminant species are
      particularly noteworthy. The diversity of saccharidic structures leads to
      multiple forms of placental glycoproteins exhibiting distinct structural and
      biological properties. For instance, concerning the chorionic gonadotrophins, the
      association of both alpha and beta subunits is essential for the binding of the
      hormone to specific receptors. Moreover, the N-linked oligossacharides are
      required for the activation of effectors systems. Bovine placental lactogen is a
      glycosylated hormone, exhibiting somatotropin- and prolactin-like activities.
      Several N-glycosylation sites confer to pregnancy-associated glycoproteins a long
      half-life (8-10 days) in maternal circulation. Assay of these molecules can be
      used for routine early pregnancy diagnosis and the follow-up of embryonic and
      fetal mortalities.

PMID- 18082643
TI  - Absence of hypogonadism in a male patient with a giant prolactinoma: a clinical
      paradox.
AB  - BACKGROUND: Impotence and decreased libido are the cardinal features of
      prolactinomas in males. We describe the unusual clinical, pathological and
      biochemical features in a male patient with a giant prolactinoma and normal
      gonadal function. CASE REPORT: A 57 year-old man presented with visual symptoms
      related to a 30x25x60mm tumor of the sella and skull base. Biopsy revealed a
      pituitary adenoma and subsequent hormone profiles demonstrated grossly elevated
      serum prolactin (131,412ng/ml), LH at the upper limit of normal and normal
      testosterone. The patient had no symptoms of decreased libido or impotence
      related to this giant prolactinoma. Immunohistochemistry revealed a tumor that
      was positive for prolactin, alpha-subunit and LH. Cabergoline greatly reduced
      prolactin levels but these remained above normal. LH, testosterone and alpha
      subunit levels were decreased in parallel. Loss of libido and impotence became
      apparent when testosterone fell below normal, a situation that resolved with
      further cabergoline treatment and prolactin inhibition and testosterone therapy.
      CONCLUSIONS: Sexual dysfunction is a hallmark of prolactinomas in males. Tumors
      that co-secrete prolactin and LH are extremely rare and this is the first such
      case reported in an adult male. In this case, normal testosterone was maintained
      by intact LH levels even in the face of the highest prolactin level reported to
      date.

PMID- 18082644
TI  - Achievements in resonance Raman spectroscopy review of a technique with a
      distinct analytical chemistry potential.
AB  - In an extended introduction, key aspects of resonance Raman spectroscopy (RRS)
      such as enhanced sensitivity and selectivity are briefly discussed in comparison
      with normal RS. The analytical potential is outlined. Then achievements in
      different fields of research are highlighted in four sections, with emphasis on
      recent breakthroughs: (1) The use of visible RRS for analyzing carotenoids in
      biological matrices, for pigments and dyes as dealt with in art and forensics,
      and for characterizing carbon nanotubes. (2) The use of RRS in the deep UV
      (excitation below 260nm) in the bioanalytical and life sciences fields, including
      nucleic acids, proteins and protein-drug interactions. Metalloproteins can be
      studied by visible RRS in resonance with their chromophoric absorption. (3)
      Progress in theoretical calculations of RRS excitation profiles and enhancement
      factors, which ultimately might facilitate analytical RRS. (4) Instrumental and
      methodological achievements including fiber-optic UV-RRS, coupling of RRS to
      liquid chromatography and capillary electrophoresis. Sensitivities can approach
      the single-molecule level with surface-enhanced RRS or tip-enhanced RRS. Last but
      not least, promising fluorescence background rejection techniques based on time
      gated detection will be presented. This review ends with a concluding section on
      future expectations for RRS, in particular its potential as an analytical
      technique.

PMID- 18082645
TI  - Biomonitoring: an appealing tool for assessment of metal pollution in the aquatic
      ecosystem.
AB  - Wide occurrence of aquatic metal pollution has caused much attention.
      Biomonitoring offers an appealing tool for the assessment of metal pollution in
      aquatic ecosystem. The bioindicators including algae, macrophyte, zooplankton,
      insect, bivalve mollusks, gastropod, fish, amphibian and others are enumerated
      and compared for their advantages and disadvantages in practical biomonitoring of
      aquatic metal pollution. The common biomonitoring techniques classified as
      bioaccumulation, biochemical alterations, morphological and behavior observation,
      population- and community-level approaches and modeling are discussed. The
      potential applications of biomonitoring are proposed to mainly include evaluation
      of actual aquatic metal pollution, bioremediation, toxicology prediction and
      researches on toxicological mechanism. Further perspectives are made for the
      biomonitoring of metal pollution in aquatic ecosystem.

PMID- 18082646
TI  - Potential of front face fluorescence associated to PLS regression to predict
      nutritional parameters in heat treated infant formula models.
AB  - This work shows that front face fluorescence spectroscopy associated to partial
      least squares (PLS) calibration is a fast and simple method to assess the
      nutritional impact of heat treatment on milk samples. Emission spectra of
      tryptophan (Trp) and of advanced Maillard products (AMP) were recorded on intact
      milk samples non-heated and heated at seven temperatures (72 degrees C, 80
      degrees C, 87 degrees C, 95 degrees C, 100 degrees C, 110 degrees C and 115
      degrees C) for six different times (from 2 min to 9.5 min) by means of front face
      fluorescence. PLS calibrations were constructed in order to indirectly quantify
      three indicators: vitamin C, protein denaturation and accumulation of Maillard
      products using the fluorescence of advanced Maillard products and soluble
      tryptophan method (FAST). The prediction models allowed obtaining an estimation
      of these indicators with a relative error of 12% for vitamin C and about 18% for
      the FAST index and soluble whey protein ratio.

PMID- 18082647
TI  - Chemometric analysis of diesel fuel for forensic and environmental applications.
AB  - Diesel fuel samples were analyzed using gas chromatography-mass spectrometry (GC
      MS) and chemometric procedures to associate and discriminate samples for
      potential use in forensic and environmental applications. Twenty-five diesel
      samples, representing 13 different brands, were collected from service stations
      in the Lansing, Michigan area. From the GC-MS data, mass-to-charge ratios were
      identified to represent aliphatic (m/z 57) and aromatic (m/z 91 and 141)
      compounds. The total ion chromatogram (TIC) and extracted ion chromatograms
      (EICs) of the chosen ions were evaluated using Pearson product moment correlation
      (PPMC) and principal component analysis (PCA). Diesel samples from the same brand
      showed higher PPMC coefficients, while those from different brands showed lower
      values. EICs generally provided a wider range of correlation coefficients than
      the TIC, with correspondingly increased discrimination among samples for EIC m/z
      91. PCA grouped the diesel samples into four distinct clusters for the TIC. The
      first cluster consisted of four samples from the same brand, two clusters
      contained one diesel sample each of different brands, and the fourth cluster
      contained the remaining diesel samples. The same trend was observed using each
      EIC, with an increase in the number of clusters formed for EIC m/z 57 and 91.
      Both statistical procedures suggest aromatic components (specifically, those with
      m/z 91) provide the greatest discrimination among diesel samples. This conclusion
      was supported by identifying the chemical components that contribute the most to
      the variance. The relative amount of aliphatic versus aromatic components was
      found to cause the greatest discrimination among samples in the data set.

PMID- 18082648
TI  - Numerical analysis of the Gran methods. A comparative study.
AB  - The paper concerns mainly the modified Gran methods, considered as extrapolative
      standard addition methods. Particularly, the approximation: [Formula: see text]
      where xi congruent with 2, is applied for the needs of the modified Gran I
      methods, in accurate and simplified versions, denoted as MG(I)A and MG(I)S
      methods. These methods are compared with Gran II methods, in original (G(II)) and
      modified accurate (MG(II)A) versions. All the methods were tested with use of
      results obtained from simulated potentiometric titrations. The effects involved
      with a pre-assumed slope vartheta(*)-value for a redox indicator electrode and in
      errors in potential (E) and volume (V) readouts on the error in equivalence
      volume (V(eq)) value thus determined is considered. It is recognized that MG(I)A
      and MG(II)A appear to be the best methods applicable for V(eq) determination
      among ones considered hitherto. Moreover, the MG(I)S method is the best choice
      for determination of the true slope theta(*)-value for the redox indicator
      electrode.

PMID- 18082649
TI  - Single hollow fiber SLM extraction of polyamines followed by tosyl chloride
      derivatization and HPLC determination.
AB  - Determination of polyamines in biological fluids possesses medical diagnostic
      relevance. Despite the vast panel of analytical methods developed for polyamines
      they are not applied in routine clinical usage, mainly due to the time and labor
      consuming sample preparation step and complicated derivatization procedures.
      Thus, new simpler methods are needed. This paper describes a single hollow fiber
      SLM extraction method of polyamines followed by simple pre-column derivatization
      with tosyl chloride and HPLC-UV analysis. The influence of different parameters
      such as the extraction time, organic phase composition, acceptor pH, donor pH,
      acceptor volume, donor volume and stirring speed on the transport parameters and
      enrichment was studied and discussed. The optimized method was applied to real
      matrices such as urine and plasma.

PMID- 18082650
TI  - On-line coupling of solid-phase extraction to high-performance liquid
      chromatography for determination of estrogens in environment.
AB  - A method based on on-line solid-phase extraction (SPE) coupling to high
      performance liquid chromatography (HPLC) for the determination of estrogens has
      been developed. This method can continuously perform extraction of estrone,
      estradiol, estriol and diethylstilbestrol from aqueous samples without any other
      pretreatment, which can then be analyzed by HPLC with a UV detector at 230 nm. A
      pre-concentration column was adapted with methanol/water for chromatographic
      separation and two kinds of sorbents were involved, which are octadecyl-bonded
      silica and cigarette filter. The condition of pH of samples, sample loading flow
      rate and desorption time were all optimized, and the performances of both two
      sorbents were satisfactory. The on-line SPE system requires very low maintenance
      and just involved a switching-valve-filter system and a flow-inject pump, and the
      operation of the whole SPE-HPLC instrumentation is quite simple. The detection
      limits for pre-concentrating 50 mL of standard solution using cigarette filter as
      sorbent ranged from 0.98 to 78.1 ngL(-1). The enhancement factors were in the
      range of 197-326. The recoveries of estrogens spiked in real water samples ranged
      from 85 to 112%. The precisions for nine replicate measurements of a standard
      mixture (5.0 microgL(-1)) were in the range of 1.0-3.4%.

PMID- 18082651
TI  - Extraction and determination of organophosphorus pesticides in water samples by a
      new liquid phase microextraction-gas chromatography-flame photometric detection.
AB  - A rapid, sensitive and efficient liquid phase microextraction (LPME) method was
      developed to determine trace concentrations of some organophosphorus pesticides
      in water samples. This method combines liquid phase microextraction with gas
      chromatographic (GC) analysis in a simple and inexpensive apparatus involving
      very little organic solvent consumption. It involves exposing a floated drop of
      an organic solvent on the surface of aqueous solution in a sealed vial.
      Experimental parameters which control the performance of LPME such as type of
      organic solvent, organic solvent and sample volumes, sample stirring rate, sample
      solution temperature, salt addition and exposure time were investigated and
      optimized. Finally, the enrichment factor, dynamic linear range (DLR), limit of
      detection (LOD) and precision of the method were evaluated by the water samples
      spiked with organophosphorus pesticides. Using optimum extraction conditions,
      very low detection limits (0.01-0.04mugL(-1)) and good linearities
      (0.9983<r(2)<0.9999) were achieved. The LPME was performed for determination of
      organophosphorus pesticides in different types of natural water samples and
      acceptable recoveries (96-104%) and precisions (3.5<R.S.D.%<8.9) were obtained.
      The results suggested that the newly proposed LPME method is a rapid, accurate
      and effective sample preparation method and could be successfully applied for
      extraction and determination of organophosphorus pesticides in water samples.

PMID- 18082652
TI  - Square wave adsorptive cathodic stripping voltammetry automated by sequential
      injection analysis Potentialities and limitations exemplified by the
      determination of methyl parathion in water samples.
AB  - This paper describes the development and evaluation of a sequential injection
      method to automate the determination of methyl parathion by square wave
      adsorptive cathodic stripping voltammetry exploiting the concept of monosegmented
      flow analysis to perform in-line sample conditioning and standard addition.
      Accumulation and stripping steps are made in the sample medium conditioned with
      40 mmolL(-1) Britton-Robinson buffer (pH 10) in 0.25 molL(-1) NaNO3. The
      homogenized mixture is injected at a flow rate of 10 microLs(-1) toward the flow
      cell, which is adapted to the capillary of a hanging drop mercury electrode.
      After a suitable deposition time, the flow is stopped and the potential is
      scanned from -0.3 to -1.0V versus Ag/AgCl at frequency of 250 Hz and pulse height
      of 25 mV. The linear dynamic range is observed for methyl parathion
      concentrations between 0.010 and 0.50 mgL(-1), with detection and quantification
      limits of 2 and 7 microgL(-1), respectively. The sampling throughput is 25 h(-1)
      if the in line standard addition and sample conditioning protocols are followed,
      but this frequency can be increased up to 61 h(-1) if the sample is conditioned
      off-line and quantified using an external calibration curve. The method was
      applied for determination of methyl parathion in spiked water samples and the
      accuracy was evaluated either by comparison to high performance liquid
      chromatography with UV detection, or by the recovery percentages. Although no
      evidences of statistically significant differences were observed between the
      expected and obtained concentrations, because of the susceptibility of the method
      to interference by other pesticides (e.g., parathion, dichlorvos) and natural
      organic matter (e.g., fulvic and humic acids), isolation of the analyte may be
      required when more complex sample matrices are encountered.

PMID- 18082653
TI  - Parallel analysis of stimulants in saliva and urine by gas chromatography/mass
      spectrometry: perspectives for "in competition" anti-doping analysis.
AB  - Stimulants are banned by the World Anti-Doping Agency (WADA) if used "in
      competition". Being the analysis of stimulants presently carried out on urine
      samples only, it might be useful, for a better interpretation of analytical data,
      to discriminate between an early intake of the substance and an administration
      specifically aimed to improve the sport performance. The purpose of the study was
      to investigate the differences, in terms of excretion/disappearance of drugs,
      between urine and oral fluid, a sample that can reflect plasmatic concentrations.
      Oral fluid and urine samples were collected following oral administration of the
      following stimulants: modafinil (100 mg), selegiline (10 mg),
      crotetamide/cropropamide (50 mg each), pentetrazol (100 mg), ephedrine (12 mg),
      sibutramine (10 mg), mate de coca (a dose containing about 3mg of cocaine);
      analysis of drugs/metabolites was carried out by gas chromatography/mass
      spectrometry (GC/MS) in both body fluids. Our results show that both the absolute
      concentrations and their variation as a function of time, in urine and in oral
      fluid, are generally markedly different, being the drugs eliminated from urine
      much more slowly than from oral fluid. Our results also suggest that the analysis
      of oral fluid could be used to successfully complement the data obtained from
      urine for "in competition" anti-doping tests; in all those cases in which the
      metabolite(s) concentration of a substance in urine is very low and the parent
      compound is not detected, it is indeed impossible, relying on urinary data only,
      to discriminate between recent administrations of small doses and remote
      administrations of higher doses.

PMID- 18082654
TI  - Dual sensing of oxygen and temperature using quantum dots and a ruthenium
      complex.
AB  - A scheme for the simultaneous determination of oxygen and temperature using
      quantum dots and a ruthenium complex is demonstrated. The luminescent complex
      [Ru(II)-tris(4,7-diphenyl-1,10-phenanthroline)]2+ is immobilized in a non
      hydrolytic sol-gel matrix and used as the oxygen sensor. The temperature
      information is provided by the luminescent emission of core-shell CdSe-ZnS
      semiconductor nanocrystals immobilized in the same material. Measurements of
      oxygen and temperature could be performed with associated errors of +/-2% of
      oxygen concentration and +/-1 degrees C, respectively. In addition, it is shown
      that while the dye luminescence intensity is quenched both by oxygen and
      temperature, the nanocrystals luminescent emission responds only to temperature.
      Results presented demonstrate that the combined luminescence response allows the
      simultaneous assessment of both parameters using a single optical fiber system.
      In particular, it was shown that a 10% error in the measured oxygen
      concentration, induced by a change in the sample temperature, could be
      compensated using the nanocrystals temperature information and a correction
      function.

PMID- 18082655
TI  - Development of an aminocarboxylic acid-modified infrared chemical sensor for
      selective determination of tyrosine in urine.
AB  - An infrared (IR) chemical sensor based on immobilization of an acidified tris(2
      aminoethyl)amine (ATAA) for the detection of tyrosine in urine is described. The
      sensing phase (i.e., coating) was saturated with nickel ions so that it would
      interact with tyrosine molecules in aqueous solution through the formation of
      stable ATAA-Ni2+-tyrosine complexes. Investigation of the signals of nine amino
      acids shows that only the three containing phenyl groups could be detected by
      this sensor system. A unique spectral feature located at 1515 cm(-1) allowed
      tyrosine to be discriminated from the other two amino acids. To examine the
      performance of the ATAA sensing phase in the quantitative analysis of tyrosine,
      the effects of several factors were examined. pH affected the ability of tyrosine
      to form complexes; the optimal signal occurred at ca. pH 8. The concentration of
      ammonia buffer also affected the analytical signals through a competition effect;
      lower concentrations of ammonia buffer provided higher intensity signals. It was
      found that nickel ions are the most useful for detection of tyrosine. Although
      the concentration of nickel ions had less influence on the analytical signal than
      did the concentration of the ammonia buffer, the signal intensity was optimal
      when the nickel ions and the target molecule had similar concentrations. The
      detected time profiles indicated that the ATAA sensor phase functioned via a
      surface adsorption mechanism. The linear range of signal intensities was up to
      600 microM with a detection limit of 30 microM.

PMID- 18082656
TI  - Isolation of Pu-isotopes from environmental samples using ion chromatography for
      accelerator mass spectrometry and alpha spectrometry.
AB  - A radiochemical method for the isolation of plutonium-isotopes from environmental
      samples, based on the use of specific extraction chromatography resins for
      actinides (TEVA), Eichrom Industries, Inc.), has been set up in our laboratory
      and optimised for their posterior determination by alpha spectrometry (AS) or
      accelerator mass spectrometry (AMS). The proposed radiochemical method has
      replaced in our lab a well-established one based on the use of a relatively un
      specific anion-exchange resin (AG) 1X8, Bio-rad Laboratories, Inc.), because it
      is clearly less time consuming, reduces the amounts and molarities of acid wastes
      produced, and reproducibly gives high radiochemical yields. In order to check the
      reliability of the proposed radiochemical method for the determination of
      plutonium-isotopes in different environmental matrixes, twin aliquots of a set of
      samples were prepared with TEVA and with AG 1X8 resins and measured by AS. Some
      samples prepared with TEVA resins were measured as well by AMS. As it is shown in
      the text, there is a comfortable agreement between AS and AMS, which adequately
      validates the method.

PMID- 18082657
TI  - Rapid determination of acetaminophen and p-aminophenol in pharmaceutical
      formulations using miniaturized capillary electrophoresis with amperometric
      detection.
AB  - Capability of fast analysis of a novel miniaturized capillary electrophoresis
      with carbon disk electrode amperometric detection (mini-CE-AD) system was
      demonstrated by determining acetaminophen and p-aminophenol in dosage forms.
      Factors influencing the separation and detection processes were examined and
      optimized. Under the optimum conditions, the end-capillary 300 microm carbon disc
      electrode amperometric detector offered favorable signal-to-noise characteristics
      at a relatively low potential (+600 mV versus Ag/AgCl) for detecting
      acetaminophen and p-aminophenol. Two analytes can been separated within 150 s in
      a 8.5 cm length capillary at a separation voltage of 2000V using a Na2B4O7-KH2PO4
      running buffer (pH 7.2). Acetaminophen and p-aminophenol could be detected down
      to the 1.4 x 10(-6)-5.9 x 10(-7) molL(-1) level with linearity up to the 1.0 x
      10(-3) molL(-1) level examined. The inter-day repeatability for analytes in peak
      current (R.S.D.< or =2.3%) and migration times (R.S.D.< or =1.3%) were excellent.
      The proposed mini-CE-AD system should find a wide range of analytical
      applications in pharmaceutical formulations as an alternative to conventional CE
      and mu-CE.

PMID- 18082658
TI  - Selectivity and recovery performance of phosphate-selective molecularly imprinted
      polymer.
AB  - A phosphate-selective molecularly imprinted polymer was prepared using 1-allyl-2
      thiourea as a functional monomer, and the binding ability and selectivity of the
      polymer were evaluated. The imprinted polymer showed high binding ability to and
      selectivity for phosphate in aqueous media. The recoverability of phosphate from
      the imprinted polymer was also examined, and nearly 70% of highly concentrated
      phosphate could be recovered.

PMID- 18082659
TI  - Reducing unintended pregnancy in the United States.

PMID- 18082660
TI  - Intrauterine contraception as an alternative to interval tubal sterilization.

PMID- 18082661
TI  - Estimates of contraceptive failure from the 2002 National Survey of Family
      Growth.
AB  - BACKGROUND: In 2001, the US government's "Healthy People 2010" initiative set a
      goal of reducing contraceptive failure during the first year of use from 13% in
      1995 to 7% by 2010. We provide updated estimates of contraceptive failure for the
      most commonly used reversible methods in the United States, as well as an
      assessment of changes in failure rates from 1995 to 2002. STUDY DESIGN: Estimates
      are obtained using the 2002 National Survey of Family Growth (NSFG), a nationally
      representative sample of US women containing information on their
      characteristics, pregnancies and contraceptive use. We also use the 2001 Abortion
      Patient Survey to correct for underreporting of abortion in the NSFG. We measure
      trends in contraceptive failure between 1995 and 2002, provide new estimates for
      several population subgroups, examine changes in subgroup differences since 1995
      and identify socioeconomic characteristics associated with elevated risks of
      failure for three commonly used reversible contraceptive methods in the United
      States: the pill, male condom and withdrawal. RESULTS: In 2002, 12.4% of all
      episodes of contraceptive use ended with a failure within 12 months after
      initiation of use. Injectable and oral contraceptives remain the most effective
      reversible methods used by women in the United States, with probabilities of
      failure during the first 12 months of use of 7% and 9%, respectively. The
      probabilities of failure for withdrawal (18%) and the condom (17%) are similar.
      Reliance on fertility-awareness-based methods results in the highest probability
      of failure (25%). Population subgroups experience different probabilities of
      failure, but the characteristics of users that may predict elevated risks are not
      the same for all methods. CONCLUSION: There was no clear improvement in
      contraceptive effectiveness between 1995 and 2002. Failure rates remain high for
      users of the condom, withdrawal and fertility-awareness methods, but for all
      methods, the risk of failure is greatly affected by socioeconomic characteristics
      of the users.

PMID- 18082662
TI  - Subject and clinician experience with the levonorgestrel-releasing intrauterine
      system.
AB  - BACKGROUND: Because use of intrauterine contraception is now expanding, this
      article reports early US clinical experience with the levonorgestrel-releasing
      intrauterine system (LNG IUS) and assesses subjects' and clinicians' judgment of
      the adequacy of product information and the overall level of product satisfaction
      in order to provide insight to new providers of the LNG IUS. STUDY DESIGN:
      Multicenter, open-label, uncontrolled, Phase IIIb study. Investigators had no
      prior experience with the LNG IUS. Subjects and investigators completed surveys
      and questionnaires at 3, 6 and 12 months. RESULTS: A total of 509 women, aged 18
      to 45 years, were enrolled in this study between July 2000 and June 2002, and 506
      (99.4%) received a LNG IUS after the first (488/506, 95.9%) or second (18/20,
      90%) insertion attempt. Insertion was rated as "easy" by 91.8% of investigators.
      Continuation rate at 12 months was 79%. Primary reasons for premature
      discontinuation were expulsion (4.5%) and menstrual cycle problems (3.8%). Most
      subjects (84.5%) indicated a high level of satisfaction with the LNG IUS.
      CONCLUSION: Over 95% of women had successful insertions of the LNG IUS at first
      attempt, and less than 1% were unsuccessful after two attempts. Both clinicians
      and subjects were highly satisfied with product information and their experience
      with the LNG IUS. One-year continuation rates were comparable to those of other
      reversible methods.

PMID- 18082663
TI  - Cytological evaluation and investigation of the vaginal flora of long-term users
      of the levonorgestrel-releasing intrauterine system (LNG-IUS).
AB  - BACKGROUND: The study was conducted to evaluate the cytopathological findings and
      vaginal flora in cervical smear samples from women using the levonorgestrel
      releasing intrauterine system (LNG-IUS) for a period of up to 7 years. STUDY
      DESIGN: Postinsertion cytology examinations were conducted on 187 women who had
      an LNG-IUS inserted between April and September 1998 in the family planning
      clinic of the Universidade Estadual de Campinas. RESULTS: During the 7 years of
      follow-up, a high frequency of candidiasis was found from the fourth through the
      seventh year of use in comparison to the first year of use. No significant
      results were found with respect to cytopathological abnormalities or other
      microbiological alterations following insertion of the LNG-IUS. CONCLUSION: Use
      of the LNG-IUS had no effect on cervical smears over the 7-year follow-up period;
      however, an increase occurred in the frequency of candidiasis.

PMID- 18082664
TI  - Effects on serum hormone levels of low-dose estrogen in place of placebo during
      the hormone-free interval of an oral contraceptive.
AB  - BACKGROUND: The study was conducted to evaluate the effects of low-dose estrogen
      compared to placebo on ovarian activity during the traditional 7-day hormone-free
      interval (HFI) of an oral contraceptive (OC). STUDY DESIGN: Women were randomized
      to placebo or low-dose estrogen for 7 days during the HFI. Serum levels of
      estradiol, follicle-stimulating hormone (FSH), luteinizing hormone and inhibin B
      were obtained before, during and after treatment. RESULTS: Mean hormone levels
      remained constant or only increased slightly for the low-dose estrogen group
      compared to greater more sustained increases observed for the placebo group.
      Estradiol, FSH and inhibin B levels were substantially higher for those on
      placebo. Differences were most noticeable by the end of the HFI and persisted
      into the subsequent cycle. CONCLUSION: Subjects receiving low-dose estrogen for 7
      days during the HFI demonstrated more pronounced ovarian suppression compared to
      placebo as evidenced by attenuation of increases in serum inhibin B, FSH and
      estradiol levels.

PMID- 18082665
TI  - Self pregnancy testing in an urban family planning clinic: promising results for
      a new approach to contraceptive follow-up.
AB  - BACKGROUND: Immediate initiation of depo-medroxyprogesterone acetate (DMPA)
      increases continuation and decreases pregnancies compared to conventional (next
      menstrual period) initiation. A drawback is the need to return in 4 weeks for a
      repeat pregnancy test to identify any pregnancy that was too early to diagnose on
      the day of injection. If women can perform home pregnancy tests (HPTs) to detect
      human chorionic gonadotropin (hCG) in urine, the need for this follow-up visit
      may be eliminated. This study assesses whether women can perform their own HPT.
      STUDY DESIGN: This is a single-visit observational trial of an HPT kit. Subjects
      recruited from a waiting room in an urban family planning clinic received an HPT
      kit with standard instructions to use immediately. Subjects and a research
      assistant each interpreted the test. Their results were then compared to a
      standard cassette type test for detection of hCG performed by clinic staff. kappa
      was calculated to assess the level of agreement. RESULTS: Three hundred ten
      subjects enrolled. They were young (mean age, 25.2 years), mostly Hispanic (91%)
      women. A change in the font and explicitness of the instructions decreased the
      incidence of invalid tests from 12.7% to 4.8%. The subject and research
      assistant's interpretation of the test had a high level of agreement, kappa=0.95
      [95% confidence interval (CI), 0.92-0.99]. There was also a high level of
      agreement between the subjects' results and the standard test, kappa=0.88 (95%
      CI, 0.82-0.95). CONCLUSIONS: Women presenting for pregnancy testing at an urban
      clinic are able to perform HPTs with a high level of accuracy. The appearance of
      the instructions influenced the incidence of false-negative and invalid tests.
      Home pregnancy tests may be useful in follow-up protocols when immediate
      initiation of DMPA is employed.

PMID- 18082666
TI  - A qualitative study of barriers to postpartum sterilization and women's attitudes
      toward unfulfilled sterilization requests.
AB  - BACKGROUND: This longitudinal, qualitative study explores barriers to postpartum
      sterilization from the perspective of low-income minority women. We examine
      women's feelings and attitudes regarding a canceled or postponed procedure over
      time. STUDY DESIGN: We conducted structured, in-depth baseline interviews with 34
      postpartum women with unfulfilled sterilization requests in a university hospital
      setting. Follow-up phone interviews were conducted at 6 weeks and 6 months
      postpartum. RESULTS: Reasons for unfulfilled sterilization requests included last
      minute misgivings, maternal medical complications, lack of a valid Medicaid
      consent form, fear of the procedure and provider influence. Sense of autonomy
      regarding sterilization decision making and ability to obtain interval
      sterilization or initiate and/or successfully use reversible contraception
      influenced subsequent attitudes regarding an unfulfilled request. CONCLUSIONS:
      Sterilization counseling should include comprehensive information regarding the
      surgical procedure and associated risks and the development of a backup
      contraceptive plan, with particular emphasis on increasing contraceptive self
      efficacy and autonomy in sterilization decision making.

PMID- 18082667
TI  - Second-trimester pregnancy termination with 600-microg vs. 400-microg vaginal
      misoprostol and systematic curettage postexpulsion: a randomized trial.
AB  - BACKGROUND: This study was conducted to compare efficacy and safety of 600 mcg of
      misoprostol vaginally every 6 h up to four doses vs. 400 mcg of misoprostol
      vaginally every 4 h up to five doses, followed by systematic curettage of the
      uterine cavity, for pregnancy termination between 12 and 20 weeks' gestation.
      STUDY DESIGN: We used a randomized clinical trial conducted at Hospital Gineco
      Obstetrico "Eusebio Hernandez", Havana, Cuba. Subjects were women requesting
      voluntary termination of pregnancies between 12 and 20 weeks' gestation. Two
      hundred ten women were randomly assigned to receive 600 mcg of vaginal
      misoprostol every 6 h up to four doses (Group I) vs. 400 mcg of vaginal
      misoprostol every 4 h up to five doses (Group II), followed by curettage 1 h
      after expulsion. The main outcomes measured were successful abortion rate and
      mean expulsion time. RESULTS: Successful abortion occurred in 103/105 women
      (98.1%) in Group I and in 99/105 (94.3%) in Group II [p=.279, relative risk
      (RR)=3.121 and 95% confidence interval for RR=0.615 to 15.833]. Fetus mean
      expulsion time was 10.7+/-1.3 (SD) h in Group I and 11.5+/-5.0 (SD) h in Group II
      (p=.209). CONCLUSIONS: Six hundred micrograms of misoprostol administered
      vaginally every 6 h was as effective as 400 mcg of misoprostol every 4 h for
      second-trimester pregnancy termination.

PMID- 18082668
TI  - A randomized trial of tramadol versus ibuprofen as an adjunct to pain control
      during vacuum aspiration abortion.
AB  - BACKGROUND: The study was conducted to determine whether tramadol is more
      effective than ibuprofen for reducing pain during uterine aspiration for
      abortion. STUDY DESIGN: Women presenting to a community-based abortion clinic
      were invited to participate in this double-blind, randomized trial. Following
      informed consent, subjects were randomly assigned to receive either 50 mg
      tramadol or 800 mg ibuprofen orally in addition to the standard clinic analgesic
      protocol. The primary outcome was pain as verbally rated on a scale from 0 to 10.
      Measurements were obtained immediately after and 30 min postprocedure. RESULTS:
      One hundred fifty-eight women were enrolled, 80 women were randomized to
      ibuprofen and 78 women, to tramadol. Immediately after the procedure, the mean
      pain scores in both treatment groups were 4.9 (95% CI=4.3-5.5). Thirty min
      postoperatively the mean pain score in the ibuprofen group was 2.8 compared to
      3.6 in the tramadol group (p=.04). CONCLUSION: There was no difference in
      immediate postprocedure pain between women receiving tramadol or ibuprofen.
      Ibuprofen is somewhat more effective than tramadol at reducing pain 30 min
      following surgical abortion.

PMID- 18082669
TI  - The effect of consolidation of abortion services on patient outcomes.
AB  - BACKGROUND: In 2001, a service dedicated to family planning was created within a
      large public hospital to improve patient care services. This retrospective chart
      review demonstrates the benefit of focusing these services in a specialty clinic.
      STUDY DESIGN: A power analysis was performed and determined that a minimum of 136
      charts were needed in each arm of the study to determine if, following an
      elective abortion, there was a significant increase in attendance at the
      scheduled postoperative visit. Secondary variables included analysis of
      contraceptive choice, incidence of continuation of injectable contraception and
      incidence of repeat pregnancy. RESULTS: After counseling services were initiated,
      there was a 27% increase in the number of patients returning for the
      postoperative clinic appointment within 8 weeks [32% (61/191) in 1998 vs. 59%
      (80/136) in 2001; p<.0001]. There was also a significant decrease in patients
      without a plan for contraception, 29% in 1998 vs. 11% in 2001, and a decrease in
      repeat pregnancies from 9% in 1998 to 1.5% in 2001. There was no difference in
      patient adherence with injectable contraception. CONCLUSION: Consolidation of
      abortion services improves subsequent use of contraception and reduces incidence
      of repeat pregnancy.

PMID- 18082671
TI  - Recommendations for standardized definitions of "bleeding" and "spotting".

PMID- 18082672
TI  - The immunocytokine scFv23/TNF targeting HER-2/neu induces synergistic cytotoxic
      effects with 5-fluorouracil in TNF-resistant pancreatic cancer cell lines.
AB  - Human pancreatic tumor cells are highly resistant to both tumor necrosis factor
      (TNF) and to chemotherapeutic agents. HER-2/neu expression has been proposed as a
      negative prognostic marker in pancreatic intraepithelial neoplasia. Our approach
      was to utilize HER-2/neu expression on the surface of tumor cells as a
      therapeutic target employing scFv23/TNF, immunocytokine composed of a single
      chain Fv antibody (scFv23) targeting the HER-2/neu and the cytokine TNF as the
      cytotoxic moiety, to deliver TNF directly to TNF-resistant pancreatic tumor
      cells. Using a panel of human pancreatic cell lines, which overexpress HER-2/neu,
      we evaluated the in vitro response of cells to TNF, scFv23/TNF, Herceptin, and a
      combination of scFv23/TNF with various chemotherapeutic agents. We found that all
      pancreatic cancer cell lines were highly resistant to the cytotoxic effects of
      TNF and that scFv23/TNF was highly cytotoxic to TNF-resistant HER-2/neu
      expressing pancreatic cancer cell lines at levels rivaling that of conventional
      chemotherapeutic agents. Combination studies demonstrated a synergistic cytotoxic
      effect of scFv23/TNF with 5-fluorouracil (5-FU) in TNF-resistant pancreatic
      cancer cell lines. Mechanistic studies demonstrated that the 5-FU plus scFv23/TNF
      combination specifically resulted in a down-regulation of HER-2/neu, p-Akt and
      Bcl-2 and up-regulation of TNF-R1. In addition, the combination 5-FU plus
      scFv23/TNF induced apoptosis and this synergistic effect was dependent on
      activation of caspase-8 and caspase-3. Delivery of the cytokine TNF to HER-2/neu
      expressing pancreatic tumor cells, which are inherently resistant to TNF using
      scFv23/TNF may be an effective therapy for pancreatic cancer especially when
      utilized in combination with 5-FU.

PMID- 18082673
TI  - Tyrosine depletion lowers dopamine synthesis and desipramine-induced prefrontal
      cortex catecholamine levels.
AB  - The relationship between limited tyrosine availability, DA (dopamine) synthesis
      and DA levels in the medial prefrontal cortex (MPFC) of the rat was examined by
      in vivo microdialysis. We administered a tyrosine- and phenylalanine-free mixture
      of large neutral amino acids (LNAA-) IP to lower brain tyrosine, and the
      norepinephrine transporter inhibitor desipramine (DMI) 10 mg/kg IP to raise MPFC
      DA levels without affecting DA synthesis. For examination of DOPA levels, NSD
      1015 20 microM was included in perfusate. Neither NSD-1015 nor DMI affected
      tyrosine levels. LNAA- lowered tyrosine levels by 45%, and lowered DOPA levels as
      well; this was not additionally affected by concurrent DMI 10 mg/kg IP. In
      parallel studies DMI markedly increased extracellular levels of DA (420%
      baseline) and norepinephrine (NE) (864% baseline). LNAA- had no effect on
      baseline levels of DA or NE but robustly lowered DMI-induced DA (176% baseline)
      as well as NE (237% baseline) levels. Even when DMI (20 microM) was administered
      in perfusate, LNAA- still lowered DMI-induced DA and NE levels. We conclude that
      while baseline mesocortical DA synthesis is indeed dependent on tyrosine
      availability, the MPFC maintains normal extracellular DA and NA levels in the
      face of moderately lower DA synthesis. During other than baseline conditions,
      however, tyrosine depletion can lower ECF DA and NE levels in MPFC. These data
      offer a potential mechanism linking dysregulation of tyrosine transport and
      cognitive deficits in schizophrenia.

PMID- 18082674
TI  - Retinoic acid promotes mouse splenic B cell surface IgG expression and maturation
      stimulated by CD40 and IL-4.
AB  - Retinoic acid (RA) increases antibody production in vivo but its role in B-cell
      activation is unclear. In a model of purified mouse splenic B cells stimulated by
      CD40 coreceptor (as a surrogate of T cell co-stimulation), IL-4, a principal Th-2
      cytokine, and ligation of the B-cell antigen receptor, CD40 engagement or IL-4
      alone induced B-cell activation indicated by increased Ig gamma1 germline
      transcripts, cell proliferation, and surface (s)IgG1 expression, while triple
      stimulation with the combination of anti-CD40/IL-4/anti-mu synergized to heighten
      B-cell activation. Although RA was growth inhibitory for anti-CD40-activated B
      cells, RA increased the proportion of B cells that had more differentiated
      phenotypes, such as expression of higher level of activation-induced deaminase,
      Blimp-1, CD138/syndecan-1 and sIgG1. Overall, RA can promote B-cell maturation at
      the population level by increasing the number of sIgG1 and CD138 expressing
      cells, which may be related to the potentiation of humoral immunity in vivo.

PMID- 18082675
TI  - Cyclophilin A produced by thymocytes regulates the migration of murine bone
      marrow cells.
AB  - Supernatant obtained from high dose hydrocortisone resistant thymocytes can
      induce migration of the bone marrow cell precursors to the periphery. This
      biological activity depends on the presence of the 18 kDa protein, whose amino
      acid sequence fits with the sequence of the secretory form of murine cyclophilin
      A (SP-18). Cyclophilin A isolated from the supernatant of the cortisone-resistant
      thymoma EL-4 shows its characteristic functional features as it demonstrates
      isomerase activity and binds with cyclosporine A. The cyclophilin A obtained
      manifests chemotactic activity that regulates migration of bone marrow cell
      precursors of neutrophils, T-, B- and dendritic cells.

PMID- 18082676
TI  - Grammatical pattern learning by human infants and cotton-top tamarin monkeys.
AB  - There is a surprising degree of overlapping structure evident across the
      languages of the world. One factor leading to cross-linguistic similarities may
      be constraints on human learning abilities. Linguistic structures that are easier
      for infants to learn should predominate in human languages. If correct, then (a)
      human infants should more readily acquire structures that are consistent with the
      form of natural language, whereas (b) non-human primates' patterns of learning
      should be less tightly linked to the structure of human languages. Prior
      experiments have not directly compared laboratory-based learning of grammatical
      structures by human infants and non-human primates, especially under comparable
      testing conditions and with similar materials. Five experiments with 12-month-old
      human infants and adult cotton-top tamarin monkeys addressed these predictions,
      employing comparable methods (familiarization-discrimination) and materials.
      Infants rapidly acquired complex grammatical structures by using statistically
      predictive patterns, failing to learn structures that lacked such patterns. In
      contrast, the tamarins only exploited predictive patterns when learning
      relatively simple grammatical structures. Infant learning abilities may serve
      both to facilitate natural language acquisition and to impose constraints on the
      structure of human languages.

PMID- 18082677
TI  - 2DE identification of proteins exhibiting turnover and phosphorylation dynamics
      during sea urchin egg activation.
AB  - The animal egg is a unique quiescent cell, prepackaged with maternal mRNAs and
      proteins that have functions in early development. Rapid, transient signaling at
      fertilization alters egg physiology, resulting in Ca(2+) release from the
      endoplasmic reticulum (ER) and cytoplasmic alkalinization. These events trigger
      the zygote developmental program through initiation of DNA synthesis and entry
      into mitosis. Post-translational modifications of maternal proteins are
      responsible for the spatio-temporal regulation that orchestrates egg activation.
      We used functional proteomics to identify the candidate maternal proteins
      involved in egg activation and early development. As the first step of this
      analysis, we present the data on the baseline maternal proteome, in particular,
      on proteins exhibiting changes in abundance and in phosphorylation state upon egg
      activation. We identify 94 proteins that were stable, reproducibly displayed a
      shift in isoelectric point, or changed in relative abundance at specific times
      after activation. The identities of these proteins were determined by quadrupole
      time-of-flight tandem mass spectrometry. The set of the most dynamic proteins
      appear to be enriched in intermediary metabolism proteins, cytoskeletal proteins,
      gamete associated proteins and proteins that have Ca(2+) mediated activities.

PMID- 18082678
TI  - Deletion of the Pitx1 genomic locus affects mandibular tooth morphogenesis and
      expression of the Barx1 and Tbx1 genes.
AB  - Pitx1 is a bicoid-related homeodomain factor that exhibits preferential
      expression in the developing hindlimb, mandible, pituitary gland and teeth. Pitx1
      gene-deleted mice exhibit striking abnormalities in morphogenesis and growth of
      both hindlimb and mandible, suggesting a proliferative defect in these two
      structures. Here, we studied the expression and regulation of Pitx1 in both
      mandible and developing teeth and analyzed tooth morphology, cell proliferation,
      apoptosis and expression of Pitx2, Barx1 and Tbx1 in dental tissues of Pitx1-/-
      mouse embryos. Pitx1 expression is restricted to the epithelium of the growing
      tooth anlagen. Tissue recombination and bead implantation experiments
      demonstrated that bone morphogenetic protein-4 down-regulates Pitx1 expression in
      both mandibular mesenchyme and dental epithelium. Deletion of the Pitx1 locus
      results in micrognathia and abnormal morphology of the mandibular molars.
      Although Pitx2 expression in teeth of Pitx1-/- embryos is not altered, expression
      of Barx1 decreased in the mesenchyme of the mandibular molars. Furthermore, Pitx1
      deletion results in suppression of Tbx1 expression in dental epithelium. Taken
      together, these results indicate that independent genetic pathways in mandibular
      and maxillary processes determine tooth development and morphology.

PMID- 18082679
TI  - Extraembryonic development in insects and the acrobatics of blastokinesis.
AB  - Extraembryonic development is familiar to mouse researchers, but the term is
      largely unknown among insect developmental geneticists. This is not surprising,
      as the model system Drosophila melanogaster has an extremely reduced
      extraembryonic component, the amnioserosa. In contrast, most insects retain the
      ancestral complement of two distinct extraembryonic membranes, amnion and serosa.
      These membranes are involved in several key morphogenetic events at specific
      developmental stages. The events of anatrepsis and katatrepsis--collectively
      referred to as blastokinesis--are specific to hemimetabolous insects.
      Corresponding events in holometabolous insects are simplified and lack formal
      names. All insects retain dorsal closure, which has been well studied in
      Drosophila. This review aims to resurrect both the terminology and awareness of
      insect extraembryonic development--which were last common currency in the late
      nineteenth and early twentieth centuries--as a number of recent studies have
      identified essential components of these events, through RNA interference of
      developmental genes and ectopic hormonal treatments. As much remains unknown,
      this topic offers opportunities for research on tissue specification, the
      regulation of cell shape changes and tissue interactions during morphogenesis,
      tracing the origins and final fates of cell and tissue lineages, and ascertaining
      the membranes' functions between morphogenetic events.

PMID- 18082682
TI  - Vesical prolapse in an apparently "normal" bladder.
AB  - Bladder prolapse is extremely rare in children. Reports have been limited to
      pathologic bladder conditions such as the exstrophy-epispadias complex. We report
      an interesting presentation of bladder prolapse in a child with Williams syndrome
      with an apparently normal bladder.

PMID- 18082680
TI  - Integrin beta1-mediated matrix assembly and signaling are critical for the normal
      development and function of the kidney glomerulus.
AB  - The human kidneys filter 180 l of blood every day via about 2.5 million
      glomeruli. The three layers of the glomerular filtration apparatus consist of
      fenestrated endothelium, specialized extracellular matrix known as the glomerular
      basement membrane (GBM) and the podocyte foot processes with their modified
      adherens junctions known as the slit diaphragm (SD). In this study we explored
      the contribution of podocyte beta1 integrin signaling for normal glomerular
      function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre
      beta1-fl/fl mice) are born normal but cannot complete postnatal renal
      development. They exhibit detectable proteinuria on day 1 and die within a week.
      The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium
      but show severe GBM defects with multilaminations and splitting including
      podocyte foot process effacement. The integrin linked kinase (ILK) is a
      downstream mediator of integrin beta1 activity in epithelial cells. To further
      explore whether integrin beta1-mediated signaling facilitates proper glomerular
      filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK
      fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at
      birth and die within 15 weeks of age due to renal failure. Collectively, our
      studies demonstrate that podocyte beta1 integrin and ILK signaling is critical
      for postnatal development and function of the glomerular filtration apparatus.

PMID- 18082683
TI  - An unusual case of neuroblastoma with angiomatoid features.
AB  - Neuroblastoma is the most commonly occurring solid tumor in children. Most of
      these neoplasms are diagnosed within the first few years of life. The diagnosis
      of neuroblastoma may be difficult because of its ability to arise in different
      locations, its propensity to metastasize, and variable clinical signs and
      symptoms. Therefore, accurate and timely pathologic diagnosis is imperative.
      Herein, we present the rare description of an angiomatoid neuroblastoma. Only 1
      other case has been previously reported.

PMID- 18082681
TI  - Transcriptional control of cell-cycle quiescence during C. elegans development.
AB  - During the development of the C. elegans reproductive system, cells that give
      rise to the vulva, the vulval precursor cells (VPCs), remain quiescent for two
      larval stages before resuming cell division in the third larval stage. We have
      identified several transcriptional regulators that contribute to this temporary
      cell-cycle arrest. Mutation of lin-1 or lin-31, two downstream targets of the
      Receptor Tyrosine kinase (RTK)/Ras/MAP kinase cascade that controls VPC cell
      fate, disrupts the temporary VPC quiescence. We found that the LIN-1/Ets and LIN
      31/FoxB transcription factors promote expression of CKI-1, a member of the p27
      family of cyclin-dependent kinase inhibitors (CKIs). LIN-1 and LIN-31 promote cki
      1/Kip-1 transcription prior to their inhibition through RTK/Ras/MAPK activation.
      Another mutation identified in the screen defined the mdt-13 TRAP240 Mediator
      subunit. Further analysis of the multi-subunit Mediator complex revealed that a
      specific subset of its components act in VPC quiescence. These components
      substantially overlap with the CDK-8 module implicated in transcriptional
      repression. Taken together, strict control of cell-cycle quiescence during VPC
      development involves transcriptional induction of CKI-1 and transcriptional
      regulation through the Mediator complex. These transcriptional regulators
      represent potential molecular connections between development and the basic cell
      cycle machinery.

PMID- 18082684
TI  - Spermatic cord hydatid cyst: an unusual localization.
AB  - Lesions of the groin include hernia, hydrocele, spermatic cord cyst, undescended
      testes, lymphadenopathy, and abscess. Hydatid cysts are endemic in certain
      regions of the world. They are usually located in the liver, lung, spleen, brain,
      and kidney. Although many uncommon locations have been reported, hydatid disease
      has been reported 3 times in the spermatic cord. This is the first report of a
      child with hydatid disease in the spermatic cord. A 9-year-old boy with a
      spermatic cord cyst proven to be a hydatid cyst is reported.

PMID- 18082685
TI  - Primary renal botryoid rhabdomyosarcoma: diagnosis and outcome.
AB  - Primary renal rhabdomyosarcoma is a rare entity. We report on a pediatric patient
      who, despite having multiple metastases to the lung on presentation, is free of
      disease 28 months after radical nephrectomy combined with chemotherapy and
      radiation therapy.

PMID- 18082686
TI  - Infected congenital splenic cyst associated with duodenal duplication cyst and
      malrotation--a case report.
AB  - Congenital splenic cyst is a rare entity. A potential complication of this
      anomaly is infection. We report on an 18-month-old boy who had Salmonella
      enterocolitis and 2 weeks later was found to have an infected splenic cyst. At
      surgery, a duodenal duplication cyst and malrotation of the gut were incidentally
      found. Infected splenic cysts usually occur in older children or adults. To the
      best of our knowledge, congenital splenic cyst has not previously been reported
      in association with other malformations.

PMID- 18082687
TI  - An unusual case: a giant paraesophageal hiatal hernia with intrathoracic spleen,
      preduodenal portal vein, malrotation, and left inferior vena cava.
AB  - A giant paraesophageal hiatal hernia with preduodenal portal vein, nonrotating
      gut, intrathoracic spleen, and left inferior vena cava has not been reported to
      date. This set of complex anomalies can have significant clinical implications.
      Awareness of these anomalies is essential to avoid further complications.

PMID- 18082688
TI  - Liver transplantation for multiple liver metastases from solid pseudopapillary
      tumor of the pancreas.
AB  - Solid pseudopapillary tumor (SPT) of the pancreas usually shows a benign clinical
      course. However, sometimes, distant metastasis may occur. Even in such case, the
      prognosis is good only if metastatic lesions are resected completely. We report
      the case of a 14-year-old girl with SPT of the pancreas and unresectable
      synchronous liver metastasis who underwent successful living donor liver
      transplantation. For 2 years, she has been disease free. This is the first report
      on transplantation to relieve liver metastasis of SPT.

PMID- 18082689
TI  - Toy magnet ingestion in children: revising the algorithm.
AB  - The widespread popularity of magnetic toy sets has resulted in increased reports
      of magnet ingestion and subsequent complications. Traditional algorithms for
      ingested foreign bodies have advocated passage of these objects through the
      gastrointestinal tract spontaneously. In regard to magnet ingestion, the unique
      mechanism of pathogenesis, attraction of 2 or more magnets across multiple loops
      of bowel, has led to several cases of intestinal perforation caused by bowel wall
      erosion and necrosis between the magnets. Unfortunately, a misdiagnosis and
      misconception that a solitary magnet has been ingested may lead to a delay in
      diagnosis and subsequent severe and possibly preventable complications. We report
      a case in which a child presented having thought to have ingested a solitary
      magnetic toy from a magnet construction set. This resulted in the premature
      discharge from the hospital and the patient's subsequent return with an
      intraabdominal perforation resulting in an emergency laparotomy. The recent
      increase of case reports related to magnet ingestion has resulted in proposed
      treatment regimens for patients ingesting multiple magnets. We would also
      initiate the magnet algorithm if even presumably a single magnet was ingested.
      This would include close observation and early intervention, either with
      endoscopy or surgical exploration, which would theoretically prevent the more
      severe complications, reported in the literature.

PMID- 18082690
TI  - Prenatally diagnosed patent urachus with bladder prolapse.
AB  - We report 2 cases of patent urachus with bladder prolapse, which has a
      characteristic finding of "disappearance of cyst" antenatally. In the first case,
      a 34-year-old woman presented at 14 weeks gestation for evaluation of a cyst.
      Prenatal ultrasonography revealed a cystic mass at the base of the umbilical
      cord, communicating with the bladder. At 26 weeks gestation, the cyst had
      disappeared, and a solid mass bulged out inferior to the umbilical cord. At term,
      the patient delivered a male infant. Examination of the neonate demonstrated
      mucosal protrusion inferior to the umbilical cord. Catheterization confirmed
      communication with the bladder. We diagnosed patent urachus with bladder
      prolapse. In the second case, a 36-year-old woman presented at 19 weeks gestation
      for evaluation of moderate bilateral hydronephrosis and an abdominal cyst.
      Prenatal ultrasonography revealed a cystic mass at the base of the umbilical
      cord, communicating with the bladder. At 26 weeks gestation, the cyst had
      disappeared. At term, the patient delivered a male infant displaying patent
      urachus with bladder prolapse. Understanding of the development of urachus is
      important for prenatal diagnosis, which in turn allows surgery immediately after
      birth. We showed bladder function after surgery remains good at school age.

PMID- 18082691
TI  - History of the Pacific Association of Pediatric Surgeons: the first 15 years
      (1968-1983).

PMID- 18082692
TI  - The anatomy of the cremaster muscle during inguinoscrotal testicular descent in
      the rat.
AB  - BACKGROUND: Extrapolation of rat testicular descent studies to humans has been
      criticized because of anatomical differences of the cremaster muscle. Human
      cremaster is described as a thin strip rather than a large, complete sac as in
      rats, which is proposed to be more important in propelling the testis during
      descent. This study investigated cremaster muscle anatomy and ontogeny in both
      normal and cryptorchid rat models. METHODS: Gubernacula from 4 groups of neonatal
      rats were sectioned longitudinally and transversely: normal Sprague-Dawley,
      capsaicin pretreated, flutamide pretreated, and congenital cryptorchid rats.
      Gubernacula were stained with hematoxylin-eosin, Masson trichrome, and desmin
      immunohistochemistry to study muscle development. RESULTS: Myoblasts are more
      numerous at the gubernacular tip, whereas the most differentiated muscle is
      proximal. Rat cremaster develops as an elongated strip rather than a complete sac
      derived from abdominal wall muscles. Flutamide and capsaicin pretreatment
      disrupts development. CONCLUSION: Rat cremaster muscle develops as a strip,
      bearing close resemblance to human cremaster muscle, permitting extrapolation of
      cremaster function to human testicular descent. The cremaster muscle appears to
      differentiate from the gubernacular tip during elongation to the scrotum, and
      requires intact sensory innervation and androgen.

PMID- 18082693
TI  - In vitro sensitivity of mouse esophagus to agonists in different pH medium
      values.
AB  - AIM: The aim of this study is to determine the in vitro sensitivity of mouse
      esophagus to contracting and relaxing agonists in different pH medium values.
      MATERIALS AND METHODS: Forty-eight Swiss albino mice (30-40 g) of both sexes were
      anesthetized with tiopental sodium (30 mg/kg). After exsanguinations from
      abdominal artery, esophagi were removed and suspended under 0.6 g of resting
      tension in a tissue bath containing 10 mL of Krebs solution at 37 degrees C. The
      experiments were performed in different pH mediums 7.4, 6.4, 4, and 2. Carbachol
      and acetylcholine were used as contractile agonists, and noradrenalin and
      isoproterenol to evaluate relaxation responses. Data concerning similar
      concentrations of contractile agonists obtained from different pH mediums were
      analyzed using Kruskal-Wallis nonparametric analysis of variance and post hoc
      Dunn test. Relaxation responses were compared with Student t test. A P value less
      than .05 was considered significant. The study was approved by Local Ethical
      Committee of Kirikkale University. RESULTS: Carbachol and acetylcholine caused
      concentration-dependent contractility in pH 7.4, 6.4, and 4, but contractile
      responses were inhibited in pH 2. In carbachol and acetylcholine experiments,
      there was a significant decrease in contractile responses to all concentrations
      in conjunction with a decreased in pH value. Relaxation responses in pH 2 and 4
      could not be obtained because precontraction of tissues was not possible.
      Noradrenalin and isoproterenol produced concentration-dependent relaxations in pH
      7.4 and 6.4. Although noradrenalin responses showed no significant difference
      according to pH, isoproterenol caused better relaxations in pH 6.4 (between 10(
      8) and 10(-6) mol/L) when compared to pH 7.4 studies. CONCLUSION: The mouse
      esophagus has impaired contractile responses to carbachol and acetylcholine in
      decreased pH values. Contraction responses did not occur in pH medium of 2. In
      contrast, esophagus segments showed better relaxations in lower pH values with
      isoproterenol.

PMID- 18082694
TI  - Towards a near-zero recurrence rate in laparoscopic inguinal hernia repair for
      pediatric patients of all ages.
AB  - BACKGROUND/PURPOSE: The recurrence rate in laparoscopic inguinal hernia (LIH)
      repair remains high. The aim of this study was to assess whether the introduction
      of technical improvements, including (1) decreasing tension on the purse-string
      knot when closing the internal hernia opening by injecting normal saline
      extraperitoneally, (2) using an airtight knot, and (3) stress-testing the
      airtightness of the knot by increasing intraperitoneal gas pressure, could
      eliminate recurrence in LIH repair in pediatric patients of all ages. METHODS: A
      retrospective review was performed of the prospectively collected data of 451 LIH
      repairs in 314 children of various ages in our institution from September 2002 to
      September 2006. The technical improvements mentioned above to prevent recurrence
      were introduced in the second half of the series of operations (tensionless
      repair [TL]). The data on both groups of operations were then compared. RESULTS:
      A total of 225 hernias were repaired in the first group (164 patients), compared
      with 226 in the TL group (150 patients). The differences between the ratio of
      boys to girls (129:35 vs 112:38) and the mean ages (50.84 +/- 48.15 vs 45.59 +/-
      47.95 m) in the 2 groups were not statistically significant. The recurrence rate
      in the TL group was much lower than in the first group (0.4% vs 4.88%, P = .003).
      There was no postoperative testicular atrophy in either group of patients.
      CONCLUSION: It is possible to achieve a near-zero recurrence rate in laparoscopic
      hernia repair in pediatric patients of all ages.

PMID- 18082695
TI  - The effectiveness of ureteric reimplantation during bladder augmentation for high
      grade vesicoureteric reflux in patients with neurogenic bladder: long-term
      outcome.
AB  - PURPOSE: The outcome of ureteric reimplantation (UR) during bladder augmentation
      (BA) for high-grade vesicoureteric reflux (HVUR) in patients with neurogenic
      bladder was assessed to determine the effectiveness of UR. A literature review of
      HVUR and BA was also performed. METHODS: Twenty-two consecutive
      sigmoidocolocystoplasty patients were reviewed retrospectively; 10 had unilateral
      HVUR only, 3 had bilateral HVUR, and 9 had unilateral HVUR associated with low
      grade VUR in the contralateral renal unit (RU). Preoperatively, VUR was grade V
      in 3 RU, grade IV in 22 RU, grade III in 5 RU, and grade II in 4 RU. Ureteric
      reimplantation was performed in the native bladder in 24 RU (16 patients) and in
      the colon cap in 10 RU (6 patients). RESULTS: Mean age at
      sigmoidocolocystoplasty/UR was 8.5 years (range, 2-15 years). Mean follow-up was
      12.8 years (range, 2-22 years). Postoperatively, cystourethrography showed
      residual VUR (grade IV to grade III) in only 1 RU (3%); diethylenetriamine
      pentaacetic acid scintigraphy showed no obstruction in all RU; (99m)Tc
      dimercaptosuccinic acid was improved in 13 RU, unchanged in 18 RU, and worsened
      in 3 RU; and serum creatinine remained normal in 20 patients and worsened in 2.
      Urinary tract infection, universal preoperatively, was seen postoperatively in
      only 2 patients. In the literature, 0% to 16.7% of HVUR persisted after BA alone,
      and no long-term data were available. CONCLUSIONS: Ureteric reimplantation during
      BA is safe and effective for treating HVUR in patients with neurogenic bladder.

PMID- 18082696
TI  - Is a vesicoamniotic shunt intrinsically bad? Shunting a normal fetal bladder.
AB  - INTRODUCTION: We previously demonstrated that in utero vesicoamniotic shunting of
      obstructive uropathy in fetal lambs produces a shrunken noncompliant bladder. We
      hypothesized that the normal fetal bladder filling and emptying cycle in fetal
      life is critical to the development of normal bladder function. MATERIALS AND
      METHODS: We placed vesicoamniotic shunts in 4 normal fetal lambs at 74 days'
      gestation. The fetuses were delivered at term (145 days), and bladder volume and
      compliance were measured and compared with those measurements in 3 normal term
      fetuses. The lambs were then killed and the renal tracts and bladders removed
      submitted to histologic examination. RESULTS: All shunted lambs survived to term.
      Three normal control lambs were delivered at term. The mean bladder volume in
      shunted lambs was 4 +/- 2.8 mL (n = 4) compared with 60 +/- 17 mL (n = 3) in
      control lambs (P < .05). Bladders in the shunted lambs had very poor compliance
      compared with normal lambs' bladders. Histologic examination of the shunted
      bladders showed increased fibrosis and distortion of the muscle layers compared
      with control bladders. CONCLUSION: Even in the absence of obstruction, preventing
      normal bladder filling and emptying in fetal life produces fibrotic bladders with
      poor compliance.

PMID- 18082697
TI  - Effectiveness of diaphragmatic repair using an abdominal muscle flap in patients
      with recurrent congenital diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: Recurrent congenital diaphragmatic hernia (Re-CDH) is a well
      known complication of CDH repair. Although surgical treatment is required for Re
      CDH, the question regarding which technique is the optimal treatment has not yet
      been elucidated. We performed a repair using an abdominal muscle flap (AMF) for
      Re-CDH and herein report our experience. PATIENTS AND RESULTS: Four patients
      using AMF had left Re-CDH. The patient's age at operation was around 1 year old
      in all patients. In the first repair during the neonatal period, a Gore-Tex patch
      was required for the large defect in 3 patients, whereas a primary closure was
      selected in 1 patient because the anterior diaphragm remained as a partial
      remnant. In the 3 patients in whom a Gore-Tex patch was used in the first
      operation, recurrence occurred twice. All of the patients suffered from both
      pulmonary hypertension and growth retardation. A repair using AMF (the flap of
      both the internal oblique and the transversalis abdominal muscle) was performed
      in all patients. The clinical course was good in all patients, with an
      improvement of both pulmonary hypertension and growth retardation without any
      recurrence of CDH. CONCLUSION: The use of an AMF was thus found to be an
      effective technique for repairing a large defect in Re-CDH.

PMID- 18082698
TI  - An established extracorporeal membrane oxygenation protocol promotes survival in
      extreme hypothermia.
AB  - BACKGROUND: Historical reports indicate that active rewarming with extracorporeal
      membrane oxygenation (ECMO) can salvage a patient after hypothermic cardiac
      arrest. We created a protocol that includes ECMO for extreme hypothermia to guide
      rewarming of the hypothermic patient. METHODS: A retrospective review of the ECMO
      rewarming protocol (2004-2006) was conducted. RESULTS: The active rewarming
      protocol is a flowchart that is available on our hospital intranet and can be
      accessed in the trauma bay. A severely hypothermic patient triggers the
      activation of a TRAUMA ONE-OP ECMO response. During the 2-year period, there were
      5 activations of the system and 4 children were placed on ECMO. Two of the 4 were
      dramatically salvaged and eventually discharged neurologically intact. All 5
      children were found pulseless at the scene before transport. The average time
      from the injury occurrence to arrival was 94 minutes (range, 41-181 minutes).
      Mean cardiopulmonary resuscitation time was 78.2 minutes (range, 37-152 minutes).
      The mean core temperature on arrival was 25.4 degrees C (range, 20.4 degrees C
      28.6 degrees C). The average time from arrival to ECMO cannulation was 25.5
      minutes (range, 16-37 minutes). CONCLUSION: A preemptive strategy for the
      severely hypothermic patient provides an organized approach and prompt response.
      Expeditious rewarming can make the difference in an opportunity for survival.

PMID- 18082699
TI  - Lack of distal esophageal contractions is a key determinant of gastroesophageal
      reflux disease after repair of esophageal atresia.
AB  - BACKGROUND/PURPOSE: The objective of this study is to investigate the
      characteristics of esophageal motor activity responsible for the development of
      gastroesophageal reflux (GER) in patients with esophageal atresia (EA). METHODS:
      The subjects consisted of 29 patients with EA (1 month to 19 years). Computerized
      esophageal manometry was conducted to investigate esophageal contractions at
      swallow. A topographic esophageal manometric analysis was conducted in each
      subject, providing 3-dimensional displays to reveal the pressure continuum
      representing esophageal contractions. RESULTS: Significant contractions in the
      middle esophagus just below the anastomosis were absent in all subjects.
      Contractions in the distal esophagus were conspicuously absent in 17 subjects. Of
      these 17, 6 had already undergone fundoplication, and 9 had symptomatic GER
      requiring fundoplication subsequent to this study. The remaining 12 patients had
      contractions in the distal esophagus and did not require medical/surgical
      intervention. A lack of distal esophageal contractions was significantly
      correlated with the development of GER (P < .001). There was a significant
      difference in esophageal acid exposure between the 2 groups (median, 38% vs 4%, P
      < .001). CONCLUSION: Lack of distal esophageal contractions indicating an
      impaired clearing capacity is considered a potential key determinant of GER in
      patients with EA.

PMID- 18082700
TI  - Robotic fundoplication in children: resident teaching and a single institutional
      review of our first 50 patients.
AB  - BACKGROUND: Robotic surgery is a new technology that may eventually replace
      laparoscopy in treating many surgical issues in children. Resident education
      using robotic surgery has been a concern for many institutions. We present our
      first 50 consecutive robotic fundoplications in children and our teaching
      experience with this procedure. METHOD: A 3-arm surgical robot was used to create
      a Nissen fundoplication with 1 additional port for liver retraction. Although
      there were exceptions, a 12-mm 3-dimensional camera was used in most patients
      greater than 10 kg, and a 5-mm 2-dimensional camera if less than 10 kg. Robotic
      instruments were either 8 or 5 mm. An accessory port was used for liver
      retraction. The console surgeon was either an attending surgeon or a fourth-year
      general surgery resident. The general surgery residents had limited prior
      minimally invasive experience consisting of cholecystectomies, appendectomies,
      and a few other procedures. RESULTS: Average age was 5.1 years (range, 1 month to
      16 years). Average weight was 19.5 kg (range, 2.7-96.4 kg). No open conversions
      or intraoperative complications occurred. Postoperative complications included
      ileus (4%), dysphagia (4%), a G-tube site wound infection (2%), gas bloat
      syndrome (2%), and 1 wrap breakdown 3 years after the initial procedure (2%).
      Operative times for staff surgeons were down to 90 minutes after 5
      fundoplications. CONCLUSION: Robotic fundoplication is an acceptable method to
      perform minimally invasive antireflux surgery in children. Resident education and
      teaching can be readily accomplished using the robot and the learning curve is
      relatively short and steep.

PMID- 18082701
TI  - Ghosts in the machine: a multi-institutional comparison of laparoscopic and open
      pyloromyotomy.
AB  - INTRODUCTION: The purpose of this study was to compare laparoscopic and open
      pyloromyotomy using data from multiple centers in the United States. METHODS:
      Children's hospitals that have a predominant surgical approach to pyloromyotomy
      were identified in the Pediatric Health Information System database. Using 2005
      data, institutions were stratified into open (OPEN) and laparoscopic (LAP)
      groups. Patients with significant comorbid conditions were excluded. Group
      differences were compared using t tests and Mann-Whitney nonparametric tests for
      continuous variables and exact tests for categorical variables. RESULTS: A total
      of 3 hospitals were in the LAP group (n = 207), and 4 hospitals were in the OPEN
      group (n = 357). The LAP group had a longer mean length of stay (LAP = 2.5 +/-
      1.7, OPEN = 2.1 +/- 1.4 days; P = .02). Mean total hospital charges were similar
      in both groups (LAP = $11307 +/- 9499, OPEN = $11245 +/- 4841; P = .93), but
      there was significant skewness of the distribution for the LAP group.
      Nonparametric analysis demonstrated a statistically significant difference in
      charges (LAP median = $9727, min = $5075, max = $94323, OPEN median = $10001, min
      = $1614, max = $46461; P = .004). Four patients in the LAP group had charges
      ranging from approximately $56000 to $94000, which may have resulted from
      surgical complications. CONCLUSION: Prolonged length of stay and skewed hospital
      charge data in patients undergoing laparoscopic pyloromyotomy may be the result
      of rare but serious complications associated with the laparoscopic approach.

PMID- 18082702
TI  - The effect analysis and comparison between gastroschisis and tracheal ligation on
      experimental diaphragmatic hernia in fetal rabbits.
AB  - PURPOSE: The authors analyzed and compared the effects of experimentally induced
      gastroschisis and tracheal ligation on pulmonary hypoplasia in fetal rabbits with
      congenital diaphragmatic hernia. METHODS: Twenty-three pregnant rabbits underwent
      fetal surgery on gestational day 24 through 27. Left diaphragmatic hernia was
      created in 1 fetus (DH group) from each rabbit, and a left diaphragmatic hernia
      with gastroschisis (GS group) or tracheal ligation (TL group) was created in
      another fetuses. The fetuses were delivered on gestational day 27 through 33.
      Histologic and morphometric examination of the lungs were performed in each
      group. RESULTS: In the DH group, the lungs were hypoplastic with a decrease in
      lung weight to body weight ratio and an increase in pulmonary arterial wall
      thickness. The alveolar septae were markedly thickened and diminished alveolar
      air spaces. In GS and TL groups, the alveolar septae were thickened but narrower
      than those of the DH group, air spaces were increased, and the pulmonary arterial
      wall was only slightly thickened. CONCLUSIONS: Pulmonary hypoplasia seen in
      newborn rabbits after experimentally induced diaphragmatic hernia is less severe
      in those rabbits with concurrently made gastroschisis or tracheal ligation. From
      the histologic viewpoint, the effects of gastroschisis and tracheal ligation on
      pulmonary hypoplasia in diaphragmatic hernia have no differences.

PMID- 18082703
TI  - Squamous cell carcinomas in children and young adults: a new wave of a very rare
      tumor?
AB  - BACKGROUND: Squamous cell carcinomas (SCCs) seem to have become more common
      recently. This study aims to check whether the increase is real and to review
      possible etiologic factors and problems in diagnosis. METHODS: Patients with SCC
      were identified from anatomical pathology files over 30 years. The number and
      primary sites seen in the first 15 years were compared with those in the second.
      Histories were reviewed for predisposing factors. Mucosal tumors were tested for
      human papillomavirus (HPV) and Epstein-Barr virus by polymerase chain reaction.
      RESULTS: One cutaneous SCC and 2 nasopharyngeal carcinomas (NPCs) were seen in
      the first period, and 2 cutaneous SCCs and 3 nasopharyngeal carcinomas in the
      second. Another 9 patients with mucosal SCCs were seen in the second period, many
      with history of cancer treatment or immunosuppression. Two laryngeal SCCs were
      HPV16-positive. Histologic diagnosis was difficult in 3 patients. CONCLUSION:
      Squamous cell carcinomas have become more common in the last 15 years. Causes
      include improved survival of cancer patients, therapeutic irradiation,
      immunosuppression, and possibly, increased prevalence of HPV in the community.
      Awareness of this increase in children, early biopsy in susceptible patients,
      repeat wider biopsy, and consultation with adult pathologists may reduce the
      diagnostic delay.

PMID- 18082704
TI  - Identification of side population cells (stem-like cell population) in pediatric
      solid tumor cell lines.
AB  - PURPOSE: Recent evidence has supported the cancer stem cell theory that cancer
      contains a small number of cancer stem cells (CSC) as a reservoir of cancer
      cells. Only the CSC, but not most of the remaining constituent cancer cells, are
      thought to be responsible for tumorigenesis, progression, and metastasis as well
      as cancer relapse, suggesting that the CSC should be targeted to eradicate the
      cancer. Side population (SP) cells isolated by fluorescence-activated cell
      sorting (FACS) using Hoechst dye are known to be enriched in stem cells in
      various normal tissues as well as cancers. The authors investigated whether such
      stem-like SP cells may exist in pediatric solid tumors (PSTs). MATERIALS AND
      METHODS: Sixteen pediatric tumor cell lines including 7 neuroblastomas, 4
      rhabdomyosarcomas, and 5 Ewing's sarcomas were used for FACS analysis. Analysis
      of SP cells based on the exclusion of the DNA binding dye, Hoechst 33342, with
      and without verapamil using FACS was performed. RESULTS: One Ewing's sarcoma cell
      line did not show an SP fraction, and only a small fraction of SP cells (0.12%
      14.6%) was detected in the other 15 cell lines. These SP cells were all sensitive
      to verapamil. CONCLUSIONS: This study suggested that most PSTs would contain a
      small fraction of SP cells (possible stem-like population). Targeting the CSC
      will provide a novel treatment strategy to eradicate refractory PSTs.

PMID- 18082705
TI  - Classification of neuroblastomas based on an analysis of the expression of genes
      related to prognosis.
AB  - PURPOSE: To select the optimal treatment according to the grade of malignancy of
      neuroblastoma (NB), it is essential to accurately and rapidly identify genetic
      abnormalities associated with the prognosis. We have identified BIN1 and
      neuronatin beta as the novel prognosis-related genes for NBs. This study aims to
      assess the correlation between the combination of the expression level of
      prognosis-related genes and the outcome of NB. METHODS: In 44 NB samples, the
      expression levels of TrkA, BIN1, and neuronatin beta were determined using
      quantitative reverse transcriptase-polymerase chain reaction; furthermore, the
      correlation between the expression of these genes' expression levels and the
      clinical progression of NB were assessed. RESULTS: It was possible to classify 44
      NBs into 4 groups regarding the grade of malignancy of NB. These 4 groups were
      all significantly associated with the clinical stages international NB staging
      system as well as the outcomes of the patients (P < .001, according to the trend
      test by Kruskal-Wallis exact test). CONCLUSION: The combination of the expression
      levels of these genes using quantitative reverse transcriptase-polymerase chain
      reaction is indicated as the effective method to quickly and accurately evaluate
      the grade of malignancy of NBs.

PMID- 18082706
TI  - Surgical resection of pulmonary metastatic lesions in children with
      hepatoblastoma.
AB  - BACKGROUND: Although the most common site of metastasis for hepatoblastoma is the
      lung, the role of thoracotomy and surgical resection of pulmonary metastasis
      remains uncertain. In this study, we aimed to determine the long-term outcome of
      patients with hepatoblastoma who have a surgical resection of pulmonary
      metastatic lesions. METHODS: Patients with hepatoblastoma in the Children's
      Oncology Group INT-0098 were reviewed. Detailed reports enabling comprehensive
      review were available for 175 of 181 eligible patients. Prognostic factors
      (histology, tumor margin, surgical complications, alpha-fetoprotein) were also
      reviewed. RESULTS: Thoracotomy for initial pulmonary metastasis: 38 patients
      presented with pulmonary metastasis, Children's Oncology Group stage IV. Nine of
      these 38 underwent thoracotomy and pulmonary metastectomy either before (2),
      simultaneous (5), or after (2) resection of their primary liver tumor. Eight of
      these 9 patients with metastectomy were long-term survivors. Thoracotomy for
      tumor relapse: 20 patients who had previously achieved complete tumor clearance
      experienced subsequent pulmonary relapse of their tumor (11 stage I or III, 9
      stage IV). All 20 patients with pulmonary relapse had salvage chemotherapy; 13
      also had thoracotomy and pulmonary metastectomy (8) or thoracotomy and biopsy
      (5). Only 4 of 13 were long-term survivors: 2 were stage I and 2 were stage IV.
      CONCLUSIONS: As pediatric surgeons, we varied tremendously in our timing and
      surgical approach to the management of pulmonary metastasis in hepatoblastoma.
      This large multicenter review suggests that thoracotomy should be used cautiously
      in the management of pulmonary relapse and perhaps more aggressively in the
      management of metastases present at diagnosis that persist after neoadjuvant
      chemotherapy.

PMID- 18082707
TI  - Increased expression of insulin-like growth factor in intestinal lengthening by
      mechanical force in rats.
AB  - INTRODUCTION: A segment of the jejunum could double its length by the application
      of an axial mechanical force. We hypothesize that this growth is correlated with
      an increased expression of insulin-like growth factor (IGF-I) in the jejunum.
      METHODS: Adult Sprague-Dawley rats underwent the isolation of a 1.5-cm segment of
      the jejunum. The isolated jejunal segment was either lengthened using mechanical
      force or left alone for 3 weeks. The jejunal segments were analyzed by
      quantitative polymerase chain reaction and immunofluorescence for the expression
      of IGF-I. RESULTS: Whereas jejunal segments that underwent isolation alone did
      not change their length, isolated jejunal segments that were stretched by
      applying a gradual mechanical force doubled their initial length. Both groups
      increased their muscular thickness 5 folds as compared to the normal jejunum. The
      mRNA level of IGF-I in the lengthened jejunum was 6 folds higher than that in the
      normal jejunum, but the IGF-I mRNA level in the isolated jejunum without
      mechanical lengthening was unchanged. By immunofluorescence, the increased IGF-I
      expression in the lengthened jejunum was localized to the intestinal smooth
      muscle cells. CONCLUSIONS: Insulin-like growth factor I may be an important
      signal induced by the applied axial force that mediates longitudinal intestinal
      growth.

PMID- 18082708
TI  - The mechanism of intestinal motility in homozygous mutant Ncx/Hox11L.1-deficient
      mice--a model for intestinal neuronal dysplasia.
AB  - PURPOSE: Homozygous mutant Ncx/Hox11L.1-deficient (Ncx-/-) mice develop mega-ileo
      ceco-colon with a caliber change in the proximal colon. This study investigated
      the mechanism of intestinal motility in these mice. METHOD: Five-week-old male
      and female Ncx-/- mice with mega-ileo-ceco-colon (n = 8) were compared with age
      matched male BDF1 mice used as controls (n = 8). All mice were sacrificed, and
      uniform-sized strips of jejunum, ileum, proximal colon, and distal colon were
      exposed to electrical field stimulation and pretreatment with atropine sulfate,
      guanethidine, or tetrodotoxin. Contractile responses were recorded and compared.
      RESULTS: Longitudinal muscle from strips of jejunum and ileum from all mice (BDF1
      and Ncx-/-) did not respond to electrical field stimulation, whereas ileal
      circular muscle contracted in BDF1 mice and contracted and relaxed in Ncx-/-
      mice. Pretreatment with atropine sulfate and guanethidine inhibited the responses
      of circular muscle of distal colon and ileum in BDF1 mice significantly (P <
      .05), but no effect was observed in Ncx-/- mice. CONCLUSION: In ileum, BDF1 mice
      have cholinergic and adrenergic dominant contraction patterns, whereas Ncx-/-
      mice have relaxation-dominant patterns because of nonadrenergic, noncholinergic
      nerves. Based on this, there would appear to be some kind of variation in the
      gastrointestinal nerve supply in Ncx-/- mice.

PMID- 18082709
TI  - Fast evaluation of intraoperative biopsies for ganglia in Hirschsprung's disease.
AB  - PURPOSE: The most important diagnostic features of Hirschsprung's disease (HD)
      are the combination of aganglionosis and hypertrophic nerve bundles.
      Acetylcholinesterase staining is widely used for diagnosis of HD as it identifies
      hypertrophic nerves in both diagnostic and intraoperative biopsies. The main
      drawback of this method is in the identification of ganglia. It has been
      suggested that the combination of this method together with another histochemical
      marker would be a superior diagnostic tool. Hematoxylin and eosin is still the
      diagnostic measure of choice for identifying ganglia in many centers, although it
      presents a persistent diagnostic challenge for pathologists trying to rapidly and
      accurately interpret the frozen biopsies that guide intraoperative decision
      making. METHODS: Therefore, we sought to develop a fast, intraoperative
      immunohistochemical protocol for visualization of ganglia and nerves in HD
      specimens that can be used in conjunction with these other tools. RESULTS: With
      the use of acetone fixation and immunofluorescence staining with antibodies to
      neurofilament 68 and tubulin, ganglia in sections of full thickness and suction
      biopsies could be visualized in only 10 minutes. This protocol facilitated the
      identification of ganglia in hematoxylin and eosin-stained adjacent sections and
      also identified hypertrophic nerve trunks. CONCLUSION: This method should
      significantly enable the identification of ganglia in suction and full thickness
      biopsies.

PMID- 18082710
TI  - A comparative study of laparoscopy-assisted pull-through and open pull-through
      for Hirschsprung's disease with special reference to postoperative fecal
      continence.
AB  - AIM: The objective of this study is to compare laparoscopy-assisted pull-through
      (LPT) and open pull-through (OPT) for Hirschsprung's disease with special
      reference to postoperative fecal continence. METHODS: Thirteen OPT patients (1991
      1996) were reviewed retrospectively, and 22 LPT (1997-2002) were reviewed
      prospectively. A continence evaluation questionnaire (CEQ, max score = 10)
      assessing frequency of motions, severity of staining, severity of perianal
      erosions, anal shape, and requirement for medications was used. Severity of
      staining was graded as none = 2, occasional = 1.5, often = 1, always = 0.5, and
      soiling = 0, and severity of staining less than or equal to 1 was defined as
      moderate to severe incontinence. Presence of fever (peak and duration), raised
      white cell count (>10,000/microL), and C-reactive protein (>0.3 mg/dL) were used
      to assess surgical stress. RESULTS: Pull-through was endorectal in all cases.
      Mean age at pull-through was not statistically different between the 2 groups.
      Annual CEQ scores for 7 years after LPT were 6.3, 6.9, 7.3, 7.7, 8.3, 8.9, and
      9.0, and after OPT were 5.6, 6.4, 7.0, 7.5, 7.8, 8.3, and 8.4. Although CEQ
      scores were higher after LPT throughout, the difference was not statistically
      significant. The incidence of moderate to severe incontinence after 4 years was
      54% (7/13) for OPT and 23% (5/22) for LPT, and after 6 years, it was 23% (3/13)
      for OPT and 0% for LPT. Duration/peak of raised C-reactive protein and duration
      of fever were significantly less for LPT (P < .01). CONCLUSION: Our results
      suggest that LPT is less invasive and may provide better postoperative bowel
      management compared with OPT.

PMID- 18082711
TI  - Anorectal sleeve micromanometry for the diagnosis of Hirschsprung's disease in
      newborns.
AB  - BACKGROUND/PURPOSE: An accurate diagnosis is mandatory for surgery in newborns
      with Hirschsprung's disease (HD). Acetylcholinesterase staining of rectal suction
      biopsy specimens is widely performed in the diagnosis of HD, but results are
      sometimes incorrect or atypical in newborns. We report the usefulness of our
      method of anorectal manometry using a specially designed sleeve microassembly for
      the diagnosis of neonatal HD. METHODS: Anorectal manometry was conducted without
      sedation in 41 newborns, aged 2 to 30 days (19 newborns were within the first
      week of life), with abdominal distension. A silastic assembly with a 2-cm-long
      sleeve sensor and 5 side holes arrayed along the sleeve was designed to reduce
      the effects of displacement of pressure sensors relative to the anal sphincter.
      Rectoanal inhibitory reflex (RAIR) was examined with rectal balloon distension.
      RESULTS: Thirty-two subjects who showed falls of anal sphincter pressure
      fulfilling the criteria for RAIR were diagnosed to be without HD. Nine patients
      without an appropriate RAIR were subsequently confirmed to have HD based on
      operative pathologic findings. Parameters of anal sphincter function did not
      differ significantly between the subjects with and without RAIR. CONCLUSIONS: An
      anorectal sleeve micromanometric technique is useful in the diagnostic workup of
      newborns suspected of having HD.

PMID- 18082712
TI  - The contribution of the sonic hedgehog cascade in the development of the enteric
      nervous system in fetal rats with anorectal malformations.
AB  - OBJECTIVE: This study was designed to determine the expression of Sonic hedgehog
      (Shh) and its downstream genes during development of the enteric nervous system
      (ENS) in ethylenethiourea (ETU)-exposed fetal rats with anorectal malformations
      (ARMs). MATERIAL AND METHODS: Anorectal malformations were induced by 1% ETU (125
      mg/kg) given on gestational day 10, and the litter was harvested at term. The
      fetal anorectum and rectosigmoid region, including any communication with the
      urinary tract, were collected for gene expression studies and immunofluorescence
      study of the ENS. Gene expression of Shh cascade was performed using reverse
      transcription and real-time polymerase chain reaction (PCR). The myenteric
      plexuses of the ENS in normal and ARM rats were visualized with fluorescent
      antibodies. RESULTS: Reverse transcription-PCR confirmed expression of Shh and
      its target genes in all parts of the ARMs. Quantitative PCR demonstrated that
      levels of expression of the genes of the Shh cascade were low in the ARMs. The
      immunoreactivity of neuromarkers was markedly reduced in high ARMs and slightly
      reduced in low ARMs. CONCLUSION: This study demonstrates reduced expression of
      Shh and its target genes in ARMs in ETU-exposed fetal rats. Neurons in the
      myenteric plexus were decreased in high and low types of ARMs. Our results
      support a role for the Shh cascade during development of the ENS during hindgut
      development.

PMID- 18082713
TI  - Pediatric treadmill injuries: a public health issue.
AB  - BACKGROUND: Treadmill injuries in children tend to be severe and are becoming
      increasingly common. We present an overview of this problem to promote public
      awareness, education, and to advocate a prevention strategy for this preventable
      injury. METHODS: Medical records of all children with treadmill-related injuries
      during a 6-year period (January 2001-November 2006) from 2 tertiary pediatric
      hospitals were reviewed. Data on patient demographics, injury related data, types
      of surgical procedure, and outcome of treatment were collected. RESULTS: Forty
      four children with treadmill-related injuries were admitted in a 6-year period
      (2001-2006). Each year, the incidence increased with 17 (39%) cases occurring in
      2006 so far. The median age of injury at the time of incident was 2.8 years
      (range, 8 months-12 years). There was a higher incidence in males (55%) compared
      with females (45%). Most of these injuries were to the hand (75%), full-thickness
      burns (59%), <1% of total burn surface area (TBSA) (73%), and occurred while the
      treadmill was in use by an adult (34%). Twenty-one (47%) children required skin
      grafting surgery. CONCLUSION: Treadmill-related burn injuries in children are a
      serious public health issue and warrants considerable attention. Adult
      supervision is paramount, and prevention strategies should include child safety
      features in equipment designs.

PMID- 18082714
TI  - Insignificant seasonal and geographical variation in incidence of biliary atresia
      in Japan: a regional survey of over 20 years.
AB  - PURPOSE: Biliary atresia (BA) is the leading cause of obstructive jaundice in the
      newborn and the major indication for liver transplantation in Japan. Viral
      infection has been implicated in its etiology because of seasonality and space
      clustering. However, this has been controversial among whites. The present study
      investigates space-time clustering of the incidence of BA in Japan. METHODS:
      Birth prevalence rates of BA were analyzed in infants born in Hyogo prefecture
      between 1985 and 2004 to assess time clustering among 3 seasons. The birth
      prevalence rates were also analyzed for space clustering between the northern
      (Hokkaido) and the southern islands (Kyushu) (difference of latitude, 10 degrees
      ) based on the Japanese Biliary Atresia Society Survey 1996-2004. We compared the
      prevalence rates between these groups using relative risks (RRs) calculated from
      2 x 2 contingency tables. RESULTS: One hundred nineteen infants were born with BA
      in Hyogo (1.1/10000 live births). Seasonal clustering in April to July did not
      significantly differ from that of the reference period (RR, 1.45; 95% confidence
      interval, 0.93-2.27). Based on Japanese registry data, space clustering between
      the northern and southern islands did not significantly differ (RR, 1.24; 95%
      confidence interval, 0.83-1.86). CONCLUSIONS: Neither seasonal nor spatial
      clustering was statistically proven in Japan.

PMID- 18082716
TI  - The evidence of maternal microchimerism in biliary atresia using fluorescent in
      situ hybridization.
AB  - BACKGROUND: Biliary atresia (BA) is a cholestatic disease of unknown etiology. It
      has recently been suggested that graft-vs-host disease caused by microchimerism
      is an etiology in the development of autoimmune disease. Moreover, the liver is a
      frequent target organ of graft-vs-host disease. The aim of this study is to
      identify the presence and extent of maternal microchimerism and to determine
      whether it plays a role in the etiology of BA. METHODS: The liver biopsy
      specimens of 6 male patients with BA (BA group) and 6 males with other liver
      diseases (non-BA group) were assayed for X- and Y-chromosome using fluorescent in
      situ hybridization. The cells with 2 sex chromosomes in the nuclei were counted.
      Cells with 1 X- and 1 Y-chromosomes were considered to be host cells, and those
      with 2 X-chromosome were considered to be of maternal origin. RESULTS: The
      frequency of cells with XX chromosomes per 1000 host cells in the BA group and
      the non-BA group were 3.00 +/- 0.75 and 0.99 +/- 0.50, respectively (P = .005).
      Moreover, the age at the time of biopsy did not affect the number of chimeric
      cells. CONCLUSION: The presence of female cells in the liver of male patients
      with BA was significantly higher than in males with other liver disease. Maternal
      microchimerism is therefore suggested to contribute to the pathogenesis of BA.

PMID- 18082715
TI  - Can biliary atresia be diagnosed by ultrasonography alone?
AB  - BACKGROUND/PURPOSE: The triangular cord sign (TCS) is a specific ultrasonographic
      finding, reflecting a fibrotic mass at the porta hepatis in biliary atresia (BA).
      We evaluated whether BA can be diagnosed by ultrasonography alone using 3
      findings: TCS, gallbladder length (GBL), and gallbladder contractility (GBC).
      METHODS: Subjects comprised 85 infants (median age, 47 days; range, 4-144 days)
      with cholestatic jaundice who underwent ultrasonographic examination for
      diagnosis between May 1996 and June 2006. Medical records were reviewed with
      regard to TCS, GBL, and GBC. Positive findings for BA included TCS >or=3 mm, GBL
      <15 mm, and GBC <68% (for < 12 weeks) or <25% (for >or=12 weeks). RESULTS:
      Biliary atresia was diagnosed in 48 patients surgically, with other cholestatic
      diseases diagnosed in the remaining 37 patients. Triangular cord sign was
      positive in 41 of 48 infants with BA and negative in 35 of 37 infants without BA.
      The 7 patients with BA who displayed negative results for TCS displayed positive
      findings for GBL or GBC. Positive predictive value in the diagnosis of BA was 98%
      if positive TCS was combined with abnormal gallbladder findings, whereas negative
      predictive value in diagnosis of BA was 100% if negative TCS was combined with
      findings of a normal gallbladder. CONCLUSIONS: Biliary atresia can be accurately
      diagnosed by ultrasonography using the findings of TCS combined with GBL and GBC.

PMID- 18082717
TI  - High-dose steroids do not improve early outcome in biliary atresia.
AB  - PURPOSE: Our objective was to evaluate the effects of steroids on early outcome
      in biliary atresia (BA). METHODS: Patients with BA between 2001 and 2005 were
      reviewed. The use of steroids (4 mg/kg per day at alternate days for 1 to 3
      months) has been routinely implemented since 2003. Jaundice-free status and the
      occurrence of cholangitis at 6 months postoperatively between patients receiving
      steroids and those not receiving steroids were compared. RESULTS: Fifty-three
      patients with BA were studied. At 6 months postoperation, 30 patients (56.6%)
      were jaundice free and 24 patients (45.3%) experienced cholangitis at least once.
      Of the 53 patients, there were 33 patients in the steroid group and 20 patients
      in the nonsteroid group. The proportion of jaundice-free patients in the steroid
      group was higher than that in the nonsteroid group, and the proportion of
      patients with cholangitis in the steroid group was lower than that in the
      nonsteroid group. However, these discrepancies did not reach a statistically
      significant difference (jaundice-free status [steroid vs nonsteroid]: 20/33
      [60.6%] vs 10/20 [50%], P = .57; cholangitis: 13/33 [39.4%] vs 11/20 [55%], P =
      .39). CONCLUSIONS: Although the use of steroids seems to have benefits, it did
      not statistically improve early outcome in patients with BA.

PMID- 18082718
TI  - Management of adult biliary atresia patients: should hard work and pregnancy be
      discouraged?
AB  - PURPOSE: The purpose of the paper was to study the potential risk and management
      of adult biliary atresia (BA) patients. MATERIALS AND METHODS: Clinical courses
      and biochemical data were retrospectively analyzed in 52 BA patients who were
      operated in our department and are now older than 15 years, with special emphasis
      on 47 patients who survived beyond the age of 20 years. RESULTS: Of these 47
      patients, 45 (95.7%) are employed, receiving higher education, and/or married.
      Thirty-three patients showed favorable liver function at the age of 20 years with
      their native liver. Thereafter, 6 (18.2%) developed liver dysfunction after
      working hard or pregnancy. In these 6 patients, cholinesterase levels were
      significantly lower at the age of 20 years than those in the 27 stable patients
      (239.5 +/- 42.6 vs 285.8 +/- 47.5, P = .0216), whereas no significant difference
      was found in alanine aminotransferase, aspartate aminotransferase, or total
      protein levels at the age of 20 years or in any biochemical parameters at the age
      of 15 years. Of the 14 transplanted patients, 5 who underwent transplantation
      after the age of 20 years had relatively uneventful courses until the age of 20
      years; however, their biochemical data already showed significant deterioration
      at puberty. CONCLUSION: Social activities and pregnancy should be managed
      individually according to the risk assessment for potential hepatic failure even
      in stable adult BA patients. A falling cholinesterase level after the age of 20
      years may predict the risk for the late hepatic dysfunction.

PMID- 18082719
TI  - The robotic approach to complex hepatobiliary anomalies in children: preliminary
      report.
AB  - PURPOSE: Robotic technology allows surgeons to perform complex procedures which
      may be difficult with standard laparoscopic instruments. We believe that complex
      hepatobiliary procedures are ideally suited for robotic surgery in children and
      present our experience with Kasai portoenterostomy and excision of choledochal
      cysts. METHODS: We performed 4 complex hepatobiliary procedures in children using
      the Da Vinci surgical robot (Intuitive Surgical, Sunnyvale, CA): 2 Kasai
      portoenterostomies and 2 choledochal cyst resections. Both Kasais had the Roux-en
      Y jejunojejunostomy performed extracorporeally through the 12 mm umbilical trocar
      site. Both choledochal cysts had the Roux-En-Y jejunojejunostomy performed
      intracorporeally. All patients had their hepatobiliary to enteric anastomosis
      performed intracorporeally. RESULTS: Total average time was 6 hours and 12
      minutes for the Kasai and 7 hours and 38 minutes for the choledochal cysts. The
      average robotic console time for all cases was 6 hours. No intraoperative or
      perioperative complications occurred. Average length of hospital stay was 4 days.
      Both choledochal cyst patients were doing well after 9 and 12 months with no
      complications. One Kasai patient is doing well 14 months after Kasai with a
      normal bilirubin. The other Kasai patient did well for a year with a normal
      bilirubin. However, the patient slowly developed intrahepatic bile lakes despite
      a normal bilirubin and a well draining Kasai as demonstrated by hepatobiliary
      iminodiacetic acid (HDA) scan. He began having recurrent episodes of cholangitis
      and we referred him for liver transplantation. CONCLUSION: Minimally invasive
      robotic complex hepatobiliary surgery is safe and effective in children. The 3
      dimensional imaging and improved articulations make these procedures particularly
      suited for robotics over standard laparoscopy.

PMID- 18082720
TI  - Fortieth Annual Meeting of the Pacific Association of Pediatric Surgeons together
      with the Annual Scientific Meeting of the Australasian Association of Pediatric
      Surgeons.

PMID- 18082721
TI  - Persistent mullerian duct syndrome and transverse testicular ectopia: embryology,
      presentation, and management.
AB  - BACKGROUND: The finding of persistent mullerian duct syndrome (PMDS) with
      transverse testicular ectopia (TTE) is rare. We present nonidentical triplets
      with PMDS with TTE. CASES: Triplet A presented with a right inguinal hernia and
      left nonpalpable testis at 4 months of age. Ultrasound demonstrated 1 testis in
      the right hemiscrotum. Laparoscopy revealed both testes in the right inguinal
      canal with a thick midline structure. Triplet B presented at 6 months of age in
      the exact manner with similar intraoperative findings as triplet A. No additional
      mullerian structures were identified in triplets A and B. Both underwent
      laparoscopic left orchiopexy and open right inguinal herniorraphy/orchiopexy. A
      portion of vas was noted in the path specimen of triplet B. Triplet C presented
      at 7 months of age with a nonpalpable left testis. Laparoscopy demonstrated
      bilateral fallopian tubes and a midline uterine remnant. Open bilateral
      orchiopexy was performed, and bilateral biopsies confirmed testes. All 3 were 46
      X,Y. CONCLUSION: Persistent mullerian duct syndrome with TTE may be encountered
      when performing laparoscopy for patients with nonpalpable testis. The persistent
      mullerian remnants vary among individuals and alter the normal anatomy, thus may
      complicate diagnosis and surgical management.

PMID- 18082722
TI  - Transmural intrathoracic lipoma with intraspinal extension.
AB  - A rare case of transmural dumbbell intrathoracic lipoma with intraspinal
      extension is reported. Preoperative diagnosis was possible with a computed
      tomographic scan and fine-needle aspiration cytology. Complete excision was
      curative. The chest wall defect was repaired with Prolene mesh. Only one similar
      case has been previously reported in the English literature.

PMID- 18082723
TI  - Challenges to cannulation for extracorporeal support in neonates with right-sided
      congenital diaphragmatic hernia.
AB  - Right-sided diaphragmatic defects represent less than 20% of all congenital
      diaphragmatic hernias (CDH). Recent data suggest that right CDH (R-CDH) may carry
      a disproportionately high morbidity as well as increased rates of extracorporeal
      support when compared with left CDH. Treatment of infants with R-CDH may be
      further complicated by anatomical distortion unique to right-sided defects. We
      report 2 cases of azygous vein cannulation in neonates with large isolated R-CDH.
      Both infants had postnatal deteriorations within 48 hours, met our criteria for
      extracorporeal membrane oxygenation (ECMO), and underwent venoarterial
      cannulations through the right neck. In each case, the venous cannula passed
      directly into the azygous vein and failed to provide adequate ECMO support.
      Echocardiography confirmed both cases of azygous cannulation. In one child, the
      right atrium was successfully cannulated after 90 minutes of extensive cannula
      manipulation. This child survived a 5-day ECMO course and is alive at 22-month
      follow-up. In the second child, despite prolonged efforts at cannula
      repositioning, cannulation of the right atrium was not achieved. We did not offer
      central cannulation because of a rapidly deteriorating clinical course, with
      expiration in several hours. At autopsy, a dilated azygous vein was evident as a
      result of inferior vena cava compression by a malpositioned liver. The
      possibility of azygous vein cannulation may be increased in neonates with R-CDH
      and has not been previously reported. When evaluating infants with R-CDH for
      ECMO, clinicians must recognize the possibility of azygous cannulation and its
      potentially lethal consequences, and should anticipate alternative venous
      cannulation.

PMID- 18082724
TI  - Splenic infarction due to concomitant hereditary spherocytosis and sickle cell
      trait.
AB  - Concomitant hereditary spherocytosis and sickle cell trait, although extremely
      rare, could potentially lead to splenic sequestration or infarction. We report
      here the first case of splenic infarction in a child with hereditary
      spherocytosis and sickle cell trait while flying on a commercial aircraft. The
      presence of hypoxia, hemoconcentrated erythrocytes, and sickle hemoglobin created
      the perfect environment for clinical sequelae.

PMID- 18082725
TI  - Sternal cleft, Morgagni hernia, and ectopic liver: a unique chest wall anomaly.
AB  - Sternal clefts are rare chest wall anomalies which may occur in isolation or in
      association with cardiac, pericardial, and diaphragmatic defects. We present the
      first report of a unique chest wall anomaly consisting of a triad of sternal
      cleft, anterior diaphragmatic hernia, and ectopic, exophytic liver tissue. A
      partial diagnosis was made on prenatal ultrasound imaging and computed tomography
      imaging of the baby's chest, but the full extent of the anomaly was only
      identified at operation. Full repair was completed on the third day of life with
      excellent outcome.

PMID- 18082726
TI  - Transumbilical management for neonatal ovarian cysts.
AB  - BACKGROUND/PURPOSE: Since Tan and Bianchi (Br J Surg. 1986;73:399) reported
      umbilical incision as an access for pyloromyotomy in infantile hypertrophic
      pyloric stenosis, many pediatric surgeons have used this approach for a number of
      other procedures. Because of the long pedicle with good mobility and the frequent
      intraabdominal position of the neonatal ovarian cyst, we attempted to manage it
      via the transumbilical route. METHODS: All patients were treated under intubation
      general anesthesia. Semicircular infraumbilical incision was made, and the
      abdomen was entered through a transverse fascial incision. The partially
      collapsed cyst after aspiration was exteriorized through the incision for
      cystectomy, partial deroofing, or adnexectomy. RESULTS: From May 2000 to December
      2006, 6 female newborns with ovarian cysts were treated via the transumbilical
      route. There were no complications from surgery. The operation time and duration
      of hospital stay were short. The cosmetic appearance after the procedure was
      good. CONCLUSIONS: The initial result suggests that transumbilical management for
      neonatal ovarian cysts may be a good alternative procedure when laparoscopic
      equipment is unavailable or experienced technique is lacking.

PMID- 18082727
TI  - Re: Watson fundoplication in children: a comparative study with Nissen
      fundoplication. Wagener S, Sudhakaran N, Cusick E. J Pediatr Surg 2007;42:1098
      1102.

PMID- 18082728
TI  - Bowel plication in the management of Hirschsprung disease.

PMID- 18082729
TI  - "Paan" in stoma care.

PMID- 18082732
TI  - Transcripts of testicular gonadotropin-releasing hormone, steroidogenic enzymes,
      and intratesticular testosterone levels in infertile men.
AB  - OBJECTIVE: To investigate the expressions of testicular GnRH and steroidogenic
      enzymes and their correlations with intratesticular T levels (ITT) and serum
      hormonal parameters in infertile men. DESIGN: Prospective case study. SETTING:
      University reproductive laboratory and clinics. PATIENT(S): Thirty-four
      azoospermic men. INTERVENTION(S): The mRNA transcript levels of GnRH-I, GnRH-II,
      GnRH-R, and five steroidogenic enzymes in the testes of azoospermic men were
      determined by quantitative real time polymerase chain reaction. The ITT level was
      determined by radioimmunoassay. MAIN OUTCOME MEASURE(S): Transcript levels of
      genes and ITT determination. RESULT(S): The mRNA transcript levels of GnRH-I,
      GnRH-II, GnRH-R, cytochrome P450 side-chain cleavage (CYP11A1), and 3beta-hydroxy
      steroid dehydrogenase type 2 enzyme (HSD3B2) as well as the ITT levels were
      significantly increased in patients with spermatogenic failure, especially in men
      with Sertoli cell-only syndrome. GnRH-I and -II mRNA transcript levels positively
      correlated with HSD3B2 mRNA transcript levels, ITT levels, and serum FSH levels.
      CONCLUSION(S): Increased testicular GnRH transcripts, steroidogenic enzyme
      transcripts, and ITT levels are associated with spermatogenic failure in
      infertile men. Testicular GnRH is involved in the regulation of human
      spermatogenesis and steroidogenesis.

PMID- 18082731
TI  - Enhancement of nitric oxide synthase induction in alveolar macrophages by in vivo
      administration of docetaxel.
AB  - Effects of docetaxel, a taxane-derivative anti-cancer drug, on lipopolysaccharide
      (LPS)-induced nitric oxide (NO) synthesis were investigated in alveolar
      macrophages isolated from rats. LPS-induced NO production and inducible NO
      synthase (iNOS) expression were significantly enhanced in the macrophages
      isolated from rats injected intraperitoneally with docetaxel (4 mg/kg body weight
      per day for 5 consecutive days) compared with those in macrophages from control
      rats administrated a vehicle. In vivo administration of docetaxel augmented LPS
      induced p38 activation but not extracellular signal-related kinase (ERK)
      activation in isolated macrophages. On the other hand, in vitro treatment of
      macrophages with docetaxel (5 and 10 microg/ml) inhibited LPS-induced NO
      production and iNOS expression. Levels of lactate dehydrogenase released from
      macrophages were neither affected by in vitro treatment with docetaxel (up to 10
      microg/ml) nor by its in vivo administration. These results suggest that
      docetaxel has an enhancing action in vivo on LPS-induced iNOS expression and
      subsequent NO production through stimulation of p38 activity in alveolar
      macrophages.

PMID- 18082733
TI  - Preliminary study on the role of the human IZUMO gene in oocyte-spermatozoa
      fusion failure.
AB  - We studied the IZUMO gene 9 coding exons sequence in four groups of patients
      including those with fertilization failure by conventional IVF. We observed in
      our populations two combinations of four polymorphisms that appeared to be
      preferentially linked (CGG-CG and TAA-TT) without any significant difference
      between different genotype repartitions.

PMID- 18082734
TI  - Malignant transformation of abdominal wall endometriosis to clear cell carcinoma:
      case report and review of the literature.
AB  - OBJECTIVE: To report a case of clear cell carcinoma in abdominal wall
      endometriosis after cesarean section. DESIGN: Case report. SETTING: A French
      oncology center. PATIENT(S): A 38-year-old woman who developed a 10-cm mass in
      the abdominal wall muscles, 13 years after a cesarean section. INTERVENTION(S):
      Abdominal wall resection and chemotherapy. MAIN OUTCOME MEASURE(S): Clinical
      outcome. RESULT(S): The diagnosis of clear cell carcinoma in abdominal wall
      endometriosis was confirmed, and wide surgical excision with abdominal wall
      reconstruction was performed after three courses of chemotherapy. CONCLUSION(S):
      The malignant transformation of abdominal wall endometrioma has not been clearly
      elucidated, owing to its rarity. However, the eventuality should always be
      considered, and the prognosis improved through wide surgical excision.

PMID- 18082735
TI  - Pregnancies associated with primary adrenal insufficiency.
AB  - OBJECTIVE: To provide a framework for the clinical presentation, evolution,
      treatment, and outcome of the unusual association between primary adrenal
      insufficiency (AI) during pregnancy and life-threatening complications for the
      mother and fetus. DESIGN: Case reports. SETTING: Pregnant women with AI treated
      in the Endocrine and Diabetes Department, Hospital Universitario de Maternidad y
      Neonatologia, Cordoba, Argentina. PATIENT(S): Three pregnant women with AI.
      INTERVENTION(S): Review of hospital records. MAIN OUTCOME MEASURE(S): Clinical,
      laboratory features, treatment, and outcome. RESULT(S): Two women with AI were
      diagnosed before conception, and one was diagnosed during gestation. Two of the
      cases were associated with other autoimmune diseases. Two newborns were born with
      signs of fetal distress, and one passed away hours later. Poor outcome was
      related to low compliance with treatment. CONCLUSION(S): AI is often overlooked
      during pregnancy because of its rarity and pregnancy-like symptoms. Nevertheless,
      other autoimmune diseases, hyponatremia, metabolic acidosis, nausea and vomiting,
      and orthostatic hypotension that does not improve with usual treatment or
      persists after first trimester should evoke a diagnosis of AI. If diagnosis and
      treatment are properly managed, pregnancy, labor, and delivery may occur without
      complications. If not, AI is associated with high maternal and fetal morbidity
      and mortality.

PMID- 18082736
TI  - DNA damage and chromosomal aberrations in various types of male factor
      infertility.
AB  - OBJECTIVE: To understand and delineate the nature and level of DNA damage in
      association to semen parameters in infertile men. DESIGN: A prospective
      experimental study. SETTING: Alexandroupolis University General Hospital.
      PATIENT(S): Eleven fertile and 27 infertile men with various types of
      infertility. INTERVENTION(S): DNA damage was induced by addition of mitomycin C
      and caffeine to lymphocyte cultures. MAIN OUTCOME MEASURE(S): Sister chromatid
      exchange (SCE) levels were assessed in cultures providing a quantitative index of
      genotoxicity and chromosomal analysis was performed using G-banding and C-banding
      techniques. RESULT(S): Karyotyping analysis indicated chromosomal fragility,
      trisomic lines, and marker chromosomes in some infertile men. Double minute
      chromosomes were noticed in 11 infertile men and were positively correlated with
      elevated SCE levels. Necrospermia and varicocele, irrespectively of the degree of
      severity, were positively correlated with elevated SCE levels. CONCLUSION(S):
      Infertile men are prone to have DNA damage; the nature and level of DNA damage
      varies and is associated with semen parameters. The presence of double minute
      chromosomes alone is associated with increased double-stranded breaks and
      abnormal sperm concentration. This study could provide the basis to establish
      whether and through which process double minute chromosomes could be related to
      poor semen parameters and regulation of DNA repair.

PMID- 18082738
TI  - Uterine relaxation by sacral surface electrical stimulation on the day of embryo
      transfer.
AB  - The peak power of uterine peristalses after sacral surface electrical stimulation
      (ssES) treatment decreased markedly in comparison with that measured before ssES
      on the day of embryo transfer (ET). This suppression effect of uterine
      peristalses was stronger on day 5 of ET than on day 3. Because the uterus at the
      time of ET is sensitive to ssES, this electrical neuromodulation may be an
      effective method to induce uterine relaxation for ET.

PMID- 18082737
TI  - Medication adherence and treatment success in the National Institute of Child
      Health and Human Development-Reproductive Medicine Network's Pregnancy in
      Polycystic Ovary Syndrome Trial.
AB  - We investigated whether poor adherence with metformin tablets may have
      contributed to the poor success rates seen in the metformin-containing arms of
      the Pregnancy in Polycystic Ovary Syndrome (PPCOS) Trial. Median adherence for
      both metformin and clomiphene citrate tablets was within acceptable limits and
      unrelated to ovulation: thus, failure to comply with physician recommendations
      for metformin dosing was not the reason for low ovulation and pregnancy rates in
      the PPCOS Trial.

PMID- 18082739
TI  - Growth hormone, insulin-like growth factor I, and leptin interaction in human
      cultured lutein granulosa cells steroidogenesis.
AB  - OBJECTIVE: To investigate the effect of leptin on the actions of growth hormone
      (GH) and insulin-like growth factor-I (IGF-I) in ovarian steroidogenesis in
      vitro. DESIGN: In vitro cell culture study. SETTING: Research laboratory of a
      university hospital. PATIENT(S): Luteinized granulosa cells (GC) were obtained
      from 20 healthy women undergoing ovarian stimulation for IVF treatment.
      INTERVENTION(S): Granulosa cells were cultured in serum free conditions for 72
      hours with either GH or IGF-I, or their combination, in the absence or presence
      of leptin (1, 10, and 100 ng/mL). MAIN OUTCOME MEASURE(S): At 24 and 72 hours of
      the culture estradiol (E(2)) and progesterone (P) concentrations were measured in
      culture supernatants by enzyme immunoassays. RESULT(S): Leptin at the doses of 1
      and 10 ng/mL significantly stimulated, whereas at the dose of 100 ng/mL it
      significantly suppressed E(2) and P production as compared to control. Estradiol
      production was significantly stimulated by both GH (72 hours) and IGF-I (24 and
      72 hours) and that of P only by IGF-I (72 hours). Leptin at the low doses
      enhanced, whereas at the high dose it suppressed the effect of GH or IGF-I on
      E(2) and P synthesis. CONCLUSION(S): These results demonstrate for the first time
      that leptin can modulate the effect of GH on steroids production by human
      luteinized GC in culture.

PMID- 18082740
TI  - Transforming growth factor (TGF)-beta1-induced human endometrial stromal cell
      decidualization through extracellular signal-regulated kinase and Smad activation
      in vitro: peroxisome proliferator-activated receptor gamma acts as a negative
      regulator of TGF-beta1.
AB  - OBJECTIVE: To investigate the effect of transforming growth factor (TGF)-beta1 on
      the extracellular signal-regulated kinase (ERK) and Smad pathway and the role of
      peroxisome proliferator-activated receptor (PPAR)-gamma in cultured human
      endometrial stromal cells. DESIGN: Experimental study. SETTING: Infertility
      center of a tertiary university hospital. MATERIAL(S): Human endometrial tissues
      obtained by hysterectomy from patients with conditions other than endometrial
      diseases. INTERVENTION(S): Endometrial stromal cells were cultured under normal
      laboratory conditions. TGF-beta1, rosiglitazone (PPARgamma agonist), and PD98059
      (ERK inhibitor) were added to endometrial stromal cell culture according to
      experimental purposes. MAIN OUTCOME MEASURE(S): Cell count, PRL expression, Smad
      and ERK phosphorylation, cyclooxygenase (COX)-2 expression, and prostaglandin
      E(2) (PGE(2)) release. RESULT(S): TGF-beta1 inhibited cellular proliferation and
      induced the expressions of COX-2, PGE(2), and PRL of cultured human endometrial
      stromal cells. These effects may be mediated by Smad and ERK phosphorylation.
      Treatment with rosiglitazone, a PPARgamma agonist, reversed the TGF-beta1 effect
      by antagonizing the activation of ERK and Smad that was induced by TGF-beta1.
      CONCLUSION(S): PPARgamma plays a negative role by directly acting on Smad and ERK
      phosphorylation in human endometrial cell decidualization that is induced by TGF
      beta1 in vitro.

PMID- 18082741
TI  - Evidence-based medicine: best practices and practice guidelines.

PMID- 18082742
TI  - Diagnostic imaging practice guidelines for musculoskeletal complaints in adults-
      an evidence-based approach: introduction.
AB  - PURPOSE: Imaging technology can improve patient outcomes by allowing greater
      precision in diagnosing and treating patients. However, there is evidence that
      overuse, underuse, and misuse of imaging services occur. The purpose of this
      project was to develop evidence-based diagnostic imaging practice guidelines for
      musculoskeletal complaints for use by doctors of chiropractic and other primary
      health care professionals. METHODS: An electronic search of the English and
      French language literature (phase 1) was conducted on several databases. Cross
      references, and references provided by clinicians, were also used. Independent
      assessment of the quality of the citations used to support recommendations in the
      guidelines was performed using the QUADAS, the AGREE,and the SPREAD evaluation
      tools. A first draft of a diagnostic imaging practice guideline was produced,
      using the European Commission's Referral Guidelines for Imaging document as a
      template. Results were sent to 12 chiropractic specialists for a first external
      review. A modified Delphi process, including 149 international experts, was used
      to generate consensus on recommendations for diagnostic imaging studies. The
      reliability of proposed recommendations was further tested on field chiropractors
      and on a group of specialists both in chiropractic and in medicine in both Canada
      and the United States. All recommendations were graded according to the strength
      of the evidence. RESULTS: The research procedure resulted in the recommendations
      for diagnostic imaging guidelines of adult extremity and spine disorders
      supported by more than 685 primary and secondary citations. High levels of
      agreement among Delphi panelists were reached for all proposed recommendations.
      Comments received by specialists were generally very favorable and reflected high
      levels of agreement with the proposed recommendations, perceived ease of use of
      guidelines, and implementation feasibility. CONCLUSIONS: These evidence-based
      diagnostic imaging practice guidelines are intended to assist chiropractors and
      other primary care providers in decision making on the appropriate use of
      diagnostic imaging for specific clinical presentations. In all cases, the
      guidelines are intended to be used in conjunction with sound clinical judgment
      and experience. Application of these guidelines should help avoid unnecessary
      radiographs, increase examination precision,and decrease health care costs
      without compromising the quality of care. All guidelines are documents to be
      refined and modified regularly with new information and experience.

PMID- 18082743
TI  - Diagnostic imaging practice guidelines for musculoskeletal complaints in adults-
      an evidence-based approach. Part 1. Lower extremity disorders.
AB  - PURPOSE: The aim of this study was to develop evidence-based diagnostic imaging
      practice guidelines to assist chiropractors and other primary care providers in
      decision making for the appropriate use of diagnostic imaging of lower extremity
      disorders. METHODS: A comprehensive search of the English and French language
      literature was conducted using a combination of subject headings and keywords.
      The quality of the citations was assessed using the Quality of Diagnostic
      Accuracy Studies (QUADAS), the Appraisal of Guidelines Research and Evaluation
      (AGREE), and the Stroke Prevention and Educational Awareness Diffusion (SPREAD)
      evaluation tools. The Referral Guidelines for Imaging (Radiation Protection 118)
      coordinated by the European Commission served as the initial template. The first
      draft was sent for external review. A Delphi panel composed of international
      experts on the topic of musculoskeletal disorders in chiropractic radiology,
      clinical sciences, and research were invited to review and propose
      recommendations on the indications for diagnostic imaging. The guidelines were
      pilot tested and peer reviewed by field chiropractors, and by chiropractic and
      medical specialists. Recommendations were graded according to the strength of the
      evidence. RESULTS: Recommendations for diagnostic imaging guidelines of adult
      lower extremity disorders are provided, supported by more than 174 primary and
      secondary citations. Except for trauma, the overall quality of available
      literature is low. On average, 57 Delphi panelists completed 1 of 2 rounds,
      reaching more than 83% agreement on all 56 recommendations. Peer review by
      specialists reflected high levels of agreement, perceived ease of use of
      guidelines, and implementation feasibility. CONCLUSIONS: The guidelines are
      intended to be used in conjunction with sound clinical judgment and experience
      and should be updated regularly. Dissemination and implementation strategies are
      discussed. Future research is needed to validate their content.

PMID- 18082744
TI  - Chiropractors as safety net providers: first report of findings and methods from
      a US survey of chiropractors.
AB  - OBJECTIVE: This study evaluates the actual or potential contribution of the
      chiropractic profession in meeting US healthcare workforce needs. METHODS: The
      authors performed a descriptive cross-sectional mail survey of US chiropractors
      in 2002 to 2003. RESULTS: The amount of charity care provided by chiropractors
      closely approximates that of medical physicians; on a weekly basis, approximately
      2 weekly hours of chiropractic care are provided for free, and 4 weekly hours are
      provided at a reduced fee. CONCLUSION: Chiropractors serve a vital, though often
      overlooked, role in the US health care safety net.

PMID- 18082746
TI  - Psychiatric illness and adverse pregnancy outcome.
AB  - OBJECTIVES: To identify the adverse effect of psychiatric illness during
      pregnancy on pregnancy outcome. METHODS: A large population-based study of
      deliveries (1988--2005) was conducted that compared women with and without
      psychiatric illness. Stratified analysis included multiple logistic regression
      models. RESULTS: Out of 181,479 deliveries, 607 (0.3%) women reported psychiatric
      illness: depressive and anxiety disorders (39%), schizophrenia (11%), or other
      psychiatric illness (50%). The psychiatric patients were significantly older,
      with higher prevalence of diabetes and hypertensive disorders. Perinatal
      mortality rate, congenital malformations, low Apgar scores, and low birth weight
      (<2500 g) were significantly increased. Multivariable logistic regression models
      determined that psychiatric illness during pregnancy is an independent risk
      factor for perinatal mortality (odds ratio [OR] 2.4; 95% CI, 1.5-3.7, P<0.001)
      and congenital malformations (OR 1.4; 95% CI, 1.01-1.9, P=0.03). CONCLUSIONS:
      Psychiatric illness is an independent risk factor for congenital malformations
      and perinatal mortality, and prenatal care should be adjusted accordingly.

PMID- 18082747
TI  - Polygamy and the use of contraceptives.
AB  - OBJECTIVES: To compare contraceptive use among women in monogamous and polygamous
      marriages in Nigeria. METHODS: Structured questionnaires administered to married
      women enquired about their marriage type, sociodemographic characteristics, and
      contraceptive use. RESULTS: Of the 532 respondents, 33.6% were in polygamous
      marriages. There was a statistically significant association between monogamy and
      nonutilization of contraception (P=0.03); however, women in polygamous marriages
      were more likely not to use contraception when they were older than 35 years, had
      4 or more living children, had no male child, had 3 or more female children, or
      lived in rural areas. There was also a statistically significant association
      between nonutilization of contraception and number of male children of co-wives
      (P=0.003), number of female children of co-wives (P=0.05), and use of
      contraception by co-wives (P=0.002). CONCLUSION: Polygamy influences
      contraceptive use and the role of co-wives in this regard merits further study.

PMID- 18082745
TI  - Activation and dysregulation of the unfolded protein response in nonalcoholic
      fatty liver disease.
AB  - BACKGROUND & AIMS: Nonalcoholic fatty liver (NAFL) and nonalcoholic
      steatohepatitis (NASH) are associated with known triggers of the unfolded protein
      response (UPR). The aims were to (1) evaluate the activity of UPR in NAFL and
      NASH and (2) correlate expression of UPR pathways with liver histology. METHODS:
      Messenger RNA (mRNA) and protein expression were measured by quantitative real
      time PCR and Western blot, respectively. Apoptosis was assessed by TUNEL assay.
      Liver histology was scored using the NASH clinical research network criteria.
      RESULTS: Compared with subjects with the metabolic syndrome and normal liver
      histology (n = 17), both NAFL (n = 21) and NASH (n = 21) were associated with
      increased eukaryotic initiation factor-2alpha (eIF-2alpha) phosphorylation.
      Activating transcription factor 4 (ATF4) mRNA and protein, C/EBP homologous
      protein (CHOP), and growth arrest, DNA damage-34 (GADD34) mRNA were not increased
      in NAFL or NASH. Whereas immunoglobulin heavy chain binding protein mRNA was
      significantly increased in NASH, unspliced X-box protein-1 (XBP-1) protein did
      not increase. Also, endoplasmic reticulum degradation-enhancing alpha-mannosidase
      like protein mRNA levels were inversely related to spliced XBP-1 mRNA in NASH.
      NASH was specifically associated with low sXBP-1 protein and increased JNK
      phosphorylation. This correlated with increased TUNEL activity in NASH. The
      histologic severity correlated with sXBP-1 mRNA and JNK phosphorylation.
      CONCLUSIONS: There is a variable degree of UPR activation in NAFL and NASH.
      Although both NAFL and NASH are associated with eIF-2alpha phosphorylation, there
      is a failure to activate downstream recovery pathways, ie, ATF4-CHOP-GADD34. NASH
      is specifically associated with (1) failure to generate sXBP-1 protein and (2)
      activation of JNK.

PMID- 18082748
TI  - Resting metabolic rate and exercise capacity in women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To assess the resting metabolic rate (RMR) and exercise capacity (or
      maximal oxygen consumption [VO2 max]) of women with polycystic ovary syndrome
      (PCOS) and central adiposity. METHOD: In a cross-sectional study, RMR was
      measured by indirect calorimetry and VO2 max by the Astrand test for 31 women
      with PCOS and 29 controls matched for age and body mass index, but with a
      different body fat distribution. Differences between the means were analyzed.
      RESULTS: There were no significant differences in RMR or VO2 max values between
      the 2 groups. CONCLUSION: Central adiposity was not predictive of an altered RMR
      or of decreased exercise capacity in women with PCOS.

PMID- 18082749
TI  - Risk factors for pre-eclampsia in pregnant Chinese women with abnormal glucose
      metabolism.
AB  - OBJECTIVES: To investigate the incidence and risk factors for pre-eclampsia in
      pregnant Chinese women with abnormal glucose metabolism. METHODS: A retrospective
      cohort study was performed on 1499 pregnant women with abnormal glucose
      metabolism at Peking University First Hospital from January 1995 to December
      2004. RESULTS: The overall prevalence of pre-eclampsia in women with abnormal
      glucose metabolism was 9.4% (141/1499). The prevalence of pre-eclampsia in women
      diagnosed with diabetes mellitus prior to pregnancy was higher than that of
      gestational diabetes mellitus and gestational impaired glucose tolerance patients
      (29.1% vs 8.7% and 7.8%, P<0.01). Pre-pregnancy body mass index was significantly
      higher in women with pre-eclampsia than in those without. A higher rate of pre
      eclampsia was found in women with chronic hypertension and those with poor
      glucose control. The independent risk factors for pre-eclampsia were chronic
      hypertension and elevated pre-pregnancy body mass index. CONCLUSIONS: The type of
      diabetes, chronic hypertension, and elevated pre-pregnancy body mass index are
      high risk factors for pre-eclampsia in pregnant women with abnormal glucose
      metabolism.

PMID- 18082750
TI  - Treatment with dehydroepiandrosterone in vivo and in vitro inhibits reproduction,
      growth and viability of Taenia crassiceps metacestodes.
AB  - The aim of this work was to explore the effect of dehydroepiandrosterone (DHEA)
      on the establishment, growth and reproduction of the metacestode stage of the
      tapeworm Taenia crassiceps, both in vivo and in vitro. Administration of DHEA
      prior to infection in mice of both sexes reduced the parasite load by 50%
      compared with untreated mice. This protective effect was not associated with the
      immune response, since there was no effect of DHEA treatment on mRNA levels of IL
      2, IFN-gamma, IL-4 or IL-10. DHEA treatment of infected mice increased androgen
      receptor expression in splenocytes of both sexes. Moreover, in vitro treatment of
      T. crassiceps with DHEA reduced reproduction, motility and viability in a dose-
      and time-dependent fashion. Results indicate that DHEA has strong negative direct
      modulatory effects on murine cysticercosis. We suggest the use of hormonal
      analogues for protective purposes as a therapeutic approach to prevent murine
      cysticercosis.

PMID- 18082751
TI  - Detailed characterisation of the flow resistance of commercial sub-2 micrometer
      reversed-phase columns.
AB  - The pressure-drop characteristics of six sub-2 microm columns of three different
      manufacturers but with the same surface chemistry (C(18)) have been studied using
      the recently introduced total pore blocking method for the determination of the
      external porosity and by using scanning electron microscopy pictures to measure
      the actual size of the particles. Having used the Sauter-mean particle size to
      correctly account for the particle size spread, and having corrected for the
      influence of the intra-particle porosity, it was found that all columns yielded
      Kozeny-Carman constant (f(KC)) values close to 180, in agreement with the theory.
      This agreement could subsequently be used to quantify how the different system
      parameters such as mean particle size, packing density and intra-particle
      porosity (all tending to vary significantly from manufacturer to manufacturer)
      each contributes to the observed total bed permeability. Small (upward)
      deviations from the f(KC)=180-value could be correlated to a larger width of the
      particle size distribution, and more notably to the existence of a high size
      ratio of the largest to the smallest particles present in the particle batches.

PMID- 18082752
TI  - Novel reversed-phase high-performance liquid chromatography stationary phase with
      oligo(ethylene glycol) "click" to silica.
AB  - Oligo(ethylene glycol) (OEG) covalently bonded silica was prepared by using click
      chemistry and employed as a stationary phase for reversed-phase high-performance
      liquid chromatography. The column efficiency and effect of organic modifier
      content on retention were investigated. The separation selectivity was also
      studied with phenyl compounds and an actual sample of natural products. The
      results indicated that the stationary phase possessed good separation efficiency
      and separation selectivity in RP-HPLC mode. Moreover, the stationary phase showed
      good complementary separation selectivity to the C18 stationary phase. The OEG
      stationary phase had "clustering" function for "homologous component" in the
      separation of natural products.

PMID- 18082753
TI  - Determination of phthalates and adipate in bottled water by headspace solid-phase
      microextraction and gas chromatography/mass spectrometry.
AB  - The performance of three fibres for the headspace solid-phase microextraction
      (SPME) of di-2-ethylhexyl adipate (DEHA) and eight phthalates in water was
      investigated systematically under different extraction conditions. Good responses
      on the 65 microm polydimethylsiloxane/divinylbenzene (PDMS/DVB) SPME fibre were
      observed for DEHA and all phthalates. The polydimethylsiloxane (PDMS) SPME fibre
      had very poor responses for the lighter and slightly polar phthalates, dimethyl
      phthalate (DMP) and diethyl phthalate (DEP), while the
      divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) SPME fibre had very
      poor responses for the heavier and non-polar adipate and phthalates. The salt
      (NaCl) was found to increase the partitioning of DMP, DEP, diisobutyl phthalate
      (DiBP), di-n-butyl phthalate, and benzyl butyl phthalate (BBP) from water into
      the headspace, while partitioning of heavier adipate and phthalates from water
      into headspace was suppressed when the concentration of NaCl was above 10%. The
      automated headspace SPME methods were developed and validated under two different
      salting conditions (30% NaCl for DMP, DEP and BBP, and 10% for DEHA, DiBP, DBP,
      di-n-hexyl phthalate (DHP), di-2-ethylhexyl phthalate (DEHP), and di-n-octyl
      phthalate (DOP)). Linearity with R(2) values better than 0.9949 was observed for
      DEHA and eight phthalates over the range from 0.1 to 20 microg L(-1). Method
      detection limits ranged from 0.003 microg L(-1) for DOP to 0.085 microg L(-1) for
      BBP. Good repeatability was observed for DEHA and most phthalates with relative
      standard deviation (RSD) values less than 10%. The methods were used to analyse
      bottled water samples for DEHA and eight phthalates. DMP, DHP, BBP, DEHA and DOP
      were not detected in any samples. Concentrations of the other phthalates were low
      (around sub-ppb) except for DBP in the water from a polycarbonate bottle at 1.72
      microg L(-1).

PMID- 18082754
TI  - Preparative isolation and purification of three rotenoids and one isoflavone from
      the seeds of Millettia pachycarpa Benth by high-speed counter-current
      chromatography.
AB  - Both analytical and preparative high-speed counter-current chromatography (HSCCC)
      were used to isolate and separate chemical bioactive constituents from the seeds
      of Millettia pachycarpa Benth, a famous traditional Chinese medicine. Three
      rotenoids and one isoflavone were successfully purified for the first time by
      HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol
      water (HEMWat) (1:0.8:1:0.6, v/v/v/v). The separation parameters were first
      performed on the analytical HSCCC and optimized conditions were then scaled up to
      preparative HSCCC. The separation produced 160.2 mg tephrosin, 14.6 mg 4',5'
      dimethoxy-6,6-dimethylpyranoisoflavone, 109.4 mg deguelin, 6.7 mg 6a,12a
      dehydrodeguelin with respective purities of 95, 93, 95, 95%, in one single run
      from 400 mg crude extract of the seeds of M. pachycarpa Benth. The purity of the
      isolated compounds was analyzed by high-performance liquid chromatography (HPLC)
      and their structures were identified by electrospray ionization mass spectrometry
      (ESI-MS); (1)H nuclear magnetic resonance ((1)H NMR) and (13)C nuclear magnetic
      resonance ((13)C NMR) analysis. This paper is an excellent example of the role
      that CCC is playing in isolating active compounds for pre-clinical trials of new
      chemical entities, even when scaling up between centrifuges from different
      manufacturers.

PMID- 18082755
TI  - Fluorescent high-performance liquid chromatographic analysis of vigabatrin
      enantiomers after derivatizing with naproxen acyl chloride.
AB  - Vigabatrin is widely used as an anticonvulsant in the treatment of seizures.
      Vigabatrin is usually supplied as racemate in formulation, but only the (S)-(+)
      enantiomer of vigabatrin is pharmacologically active. A simple and sensitive
      liquid chromatographic method is described for the separation and quantification
      of vigabatrin enantiomers. The method is based on derivatizing racemic vigabatrin
      with a fluorescent chiral reagent (naproxen acyl chloride). The resulting
      diastereomeric derivatives are highly responsive to a fluorimetric detector
      (lambda(ex)=230 nm, lambda(em)=350 nm). The lower quantitation limit of the
      method is attainable at 25 nM for (S)-(+)-vigabatrin or (R)-(-)-vigabatrin with a
      detection limit of about 2.5 nM (S/N=3 with 10 microl injected). Application of
      the method to the analysis of vigabatrin in serum of dosed patients proved
      feasible.

PMID- 18082756
TI  - Preparative purification of anti-tumor derivatives of honokiol by high-speed
      counter-current chromatography.
AB  - In our program to synthesize a series of novel derivatives as potential analogs
      of honokiol for anti-tumor treatment, we have found that at least three of the
      derivatives of honokiol showed more potency to inhibit the proliferation of K562
      leukemia cells and SPC-A1 adenocarcinoma cells. As a critical step to our further
      series synthesis of derivatives of honokiol, three derivatives of honokiol
      composed of two isomers and one compound with two formyl groups, which were
      hardly separated by common purification methods, needed to be rapidly separated
      and purified. The present work describes analytical and preparative high-speed
      counter-current chromatography (HSCCC) for the isolation and purification of
      these three C-formylation derivatives of honokiol, named 3'-formylhonokiol, 5
      formylhonokiol and 3',5-diformylhonokiol, respectively. The solvent system for
      HSCCC separation was composed of hexane-ethyl acetate-methanol-water with the
      ratio of 1:0.4:1:0.4 (v/v). The one-step purification produced 157.8 mg, 121.6 mg
      and 21.2 mg of 3'-formylhonokiol, 5-formylhonokiol, 3',5-diformylhonokiol from
      crude sample of 400mg with purities of 98.6%, 99.2% and 99.6%, respectively, in
      an elution time of 2.5 h. The purities and structural identification were
      determined by HPLC, (1)H NMR, (13)C NMR and mass spectroscopy. Their anti
      proliferation effects on K562, A549 and SPC-A1 cell lines were evaluated by MTT
      [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay.

PMID- 18082757
TI  - Prediction of the partitioning behaviour of proteins in aqueous two-phase systems
      using only their amino acid composition.
AB  - The prediction of the partition behaviour of proteins in aqueous two-phase
      systems (ATPS) using mathematical models based on their amino acid composition
      was investigated. The predictive models are based on the average surface
      hydrophobicity (ASH). The ASH was estimated by means of models that use the three
      dimensional structure of proteins and by models that use only the amino acid
      composition of proteins. These models were evaluated for a set of 11 proteins
      with known experimental partition coefficient in four-phase systems: polyethylene
      glycol (PEG) 4000/phosphate, sulfate, citrate and dextran and considering three
      levels of NaCl concentration (0.0% w/w, 0.6% w/w and 8.8% w/w). The results
      indicate that such prediction is feasible even though the quality of the
      prediction depends strongly on the ATPS and its operational conditions such as
      the NaCl concentration. The ATPS 0 model which use the three-dimensional
      structure obtains similar results to those given by previous models based on
      variables measured in the laboratory. In addition it maintains the main
      characteristics of the hydrophobic resolution and intrinsic hydrophobicity
      reported before. Three mathematical models, ATPS I-III, based only on the amino
      acid composition were evaluated. The best results were obtained by the ATPS I
      model which assumes that all of the amino acids are completely exposed. The
      performance of the ATPS I model follows the behaviour reported previously, i.e.
      its correlation coefficients improve as the NaCl concentration increases in the
      system and, therefore, the effect of the protein hydrophobicity prevails over
      other effects such as charge or size. Its best predictive performance was
      obtained for the PEG/dextran system at high NaCl concentration. An increase in
      the predictive capacity of at least 54.4% with respect to the models which use
      the three-dimensional structure of the protein was obtained for that system. In
      addition, the ATPS I model exhibits high correlation coefficients in that system
      being higher than 0.88 on average. The ATPS I model exhibited correlation
      coefficients higher than 0.67 for the rest of the ATPS at high NaCl
      concentration. Finally, we tested our best model, the ATPS I model, on the
      prediction of the partition coefficient of the protein invertase. We found that
      the predictive capacities of the ATPS I model are better in PEG/dextran systems,
      where the relative error of the prediction with respect to the experimental value
      is 15.6%.

PMID- 18082758
TI  - Self-assembled film based on carboxymethyl-beta-cyclodextrin and diazoresin and
      its binding properties for methylene blue.
AB  - Polyelectrolyte-layered films containing beta-cyclodextrin (beta-CD) were
      fabricated by a layer-by-layer deposition of carboxymethyl-beta-cyclodextrin (CM
      beta-CD) as a polyanion and cationic photosensitive diazoresin (DR) on a solid
      surface. Under UV irradiation, following the decomposition of diazonium group
      between the adjacent interfaces of the multilayers, the ionic bonds of the self
      assembly film convert to covalent bonds and the film become stable toward many
      common organic solvent. When a high-ionic-strength buffer is employed as a
      bathing solution, the film is thicker than that deposited from water solution.
      And the deposition increases with the increase of the carboxymethylated degree of
      CM-beta-CD. The CM-beta-CD/DR film can bind methylene blue (MB), and the
      durability of MB-adsorbing films to reductive glucose indicates that MB molecules
      not only diffuse into the film, but also load to the cavity of beta-CD through a
      host-guest complexation assisted by electrostatic interactions. The binding
      quantity of MB increases linearly with increasing the number of bilayers, and is
      influenced obviously by the pH value of MB aqueous solution. MB molecules can
      desorb from the 12-bilayer MB-absorbing CM-beta-CD/DR films when being immersed
      in water/ethanol mixture, and the released quantity of MB increases a little with
      increasing the concentration of water when it is below 30%, while decreases
      evidently over 30%.

PMID- 18082759
TI  - A study of atmospheric-pressure CHF3/Ar plasma treatment on dielectric
      characteristics of polyimide films.
AB  - In this work, the influence of atmospheric-pressure CHF(3)/Ar plasma treatment on
      surface dielectric properties of polyimide films was investigated using X-ray
      photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and contact
      angle measurements. The dielectric characteristics of the films were studied
      using a dielectric spectrometer. From the results, it was found that the plasma
      treatment introduced fluorine functional groups onto the polyimide surfaces. F
      1s/C 1s ratios of the polyimides were enhanced with the increase of plasma
      treatment time. Consequently, the fluorine groups led to a decrease of the
      surface free energy and dielectric constant of the polyimide films, which can
      largely be attributed to the decrease of the deformation polarizability or London
      dispersive component of surface free energy of the solid surface studied.

PMID- 18082760
TI  - Shape of menisci in terrestrial dewetted Bridgman growth.
AB  - Dewetted Bridgman is a crystal growth technique in which the crystal is detached
      from the crucible wall by a liquid free surface at the level of the solid-liquid
      interface, called liquid meniscus, which creates a gap between the crystal and
      the ampoule. Dewetting phenomenon was first obtained spontaneously in spatial
      experiments during the Bridgman solidification, and opened the possibility of
      reproducing experiments on the earth--obtained by applying a gas pressure
      difference Delta P=P cold-P hot between the cold and the hot sides of the sample.
      In order to understand the process which leads to a crystal with a constant
      radius on the ground, analytical and numerical studies of axisymmetric meniscus
      shapes are made and the dependence of the meniscus shape on the pressure
      difference is established. For this aim, starting from the Young-Laplace equation
      of a capillary surface in equilibrium in the presence of gas pressure, a
      mathematical model able to describe the meniscus surface z=z(r) and the angle
      theta=theta(r) between the tangent to the meniscus and the horizontal axis is
      presented. On the basis of this model, inequalities of the pressure intervals for
      which dewetting is feasible are established. Numerical results are performed for
      InSb crystals.

PMID- 18082761
TI  - Screening human antibody libraries against carcinoma cells by affinity
      purification and polymerase chain reaction.
AB  - Bacterial scFv clones from a naive antibody library have been isolated against
      cancer cell antigens with AffiSelect, a novel screening method that indirectly
      identifies candidate library members via an antigen reporter gene. The first step
      is the coating of carcinoma cell surface epitopes (antigen) with either mAbs,
      scFvs or phages (library members). Upon binding to a cell surface ligand, the
      library member generates a linking moiety. This facilitates magnetic affinity
      purification of the antibody-cancer cell complexes, detected by the polymerase
      chain reaction (PCR) using the beta-actin gene of the cancer cell as the target.
      Combining these well-known methods resulted in a higher resolution than a
      comparable cell-based ELISA method of detection. We have isolated human scFv
      antibodies against surface antigens of a lung carcinoma cell line. These were
      identified from a polyclonal mixture of phage display-enriched library clones
      comparing PCR patterns of the carcinoma cell line with the two negative cell
      types, HUVEC and peripheral blood cells (PBLs). The positive clones were
      sequenced and verified by FACS.

PMID- 18082762
TI  - Molecular structure, expression patterns, and localization of the circadian
      transcription modulator CYCLE in the cricket, Dianemobius nigrofasciatus.
AB  - CYCLE (CYC), also known as BMAL1 in vertebrate nomenclature, is a transcription
      modulator of the circadian genes period and timeless of Drosophila melanogaster.
      We cloned a cDNA encoding a CYC homologue from the head of the ground cricket,
      Dianemobius nigrofasciatus (Dncyc), the first CYC from Hemimetabola. The deduced
      sequence corresponded to a 601 amino-acid polypeptide, with well-defined bHLH,
      PAS-A, PAS-B, PAC, and BTCR domains. The amino-acid sequence showed 70.7%
      identity with the CYC protein of Athalia rosae, 63.8% with D. melanogaster, and
      52% identity with the human homologue. A cyc transcript of around 3.6kb occurs in
      the brain, midgut, testis, fatbody, and muscle. An additional band of around
      1.1kb gave a hybridization signal in the head. No temporal oscillation in cyc
      mRNA abundance was observed in the head of the adult cricket when investigated by
      Northern blot analysis. CYC-like immunohistochemical reactivity (ir) and its
      dimerization partner CLOCK (CLK)-ir appeared in the pars intercerebralis (PI),
      tritocerebrum, dorsolateral protocerebrum, and subesophageal ganglion (SOG), but
      no CYC-ir was observed in the optic lobe (OL) that showed CLK-ir. The
      deutocerebrum showed a unique CLK-ir but no CYC-ir pattern. Double-labelling
      experiments showed that both antigens were co-localized in the mandibular and
      maxillary neuromeres of the SOG. CYC-ir showed no daily oscillation in intensity
      and the staining pattern was always cytoplasmic. CLK-ir occurred in the nucleus
      at ZT 16, but was cytoplasmic at other ZT times. A neuronal network equivalent to
      adult system occurred in the second nymphal stadium.

PMID- 18082763
TI  - Susceptibility of Spodoptera exigua to 9 toxins from Bacillus thuringiensis.
AB  - Nine of the most common lepidopteran active Cry proteins from Bacillus
      thuringiensis have been tested for activity against Spodoptera exigua. Because of
      possible intraspecific variability, three laboratory strains (FRA, HOL, and MUR)
      have been used. Mortality assays were performed with the three strains. LC(50)
      values for the active toxins were determined to the FRA and the HOL strains,
      whereas susceptibility of the MUR strain was assessed using only two
      concentrations. The results showed that Cry1Ca, Cry1Da, and Cry1Fa were the most
      effective toxins with all strains. Cry1Ab was found effective for the HOL strain,
      but very little effective against FRA (6.5-fold) and MUR strains. Cry1Aa and
      Cry1Ac were marginally toxic to all strains, whereas the rest of the toxins
      tested (Cry1Ba, Cry2Aa, and Cry2Ab) were non toxic. Significant differences in
      susceptibility among strains were also found for Cry1Da, being the FRA strain 25
      fold more susceptible than the HOL strain. Growth inhibition, as an additional
      susceptibility parameter, was determined in the FRA strain with the 9 toxins. The
      toxicity profile obtained differed from that observed in mortality assays.
      Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ca, Cry1Da, and Cry1Fa toxins produced a similar
      larval growth inhibition. Cry2Aa had a lower but clear effect on larval growth
      inhibition, whereas Cry1Ba and Cry2Ab did not have any effect.

PMID- 18082764
TI  - cGMP-binding prepares PKG for substrate binding by disclosing the C-terminal
      domain.
AB  - Type I cyclic guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (PKG)
      is involved in the nitric oxide/cGMP signaling pathway. PKG has been identified
      in many different species, ranging from unicelolular organisms to mammals. The
      enzyme serves as one of the major receptor proteins for intracellular cGMP and
      controls a variety of cellular responses, ranging from smooth-muscle relaxation
      to neuronal synaptic plasticity. In the absence of a crystal structure, the three
      dimensional structure of the homodimeric 152-kDa kinase PKG is unknown; however,
      there is evidence that the kinase adopts a distinct cGMP-dependent active
      conformation when compared to the inactive conformation. We performed mass
      spectrometry-based hydrogen/deuterium exchange experiments to obtain detailed
      information on the structural changes in PKG I alpha induced by cGMP activation.
      Site-specific exchange measurements confirmed that the autoinhibitory domain and
      the hinge region become more solvent exposed, whereas the cGMP-binding domains
      become more protected in holo-PKG (dimeric PKG saturated with four cGMP molecules
      bound). More surprisingly, our data revealed a specific disclosure of the
      substrate-binding region of holo-PKG, shedding new light into the kinase
      activation process of PKG.

PMID- 18082765
TI  - Transcriptional stability of cultured cells upon prion infection.
AB  - Prion infections induce severe disruption of the central nervous system with
      neuronal vacuolation and extensive glial reactions, and invariably lead to death
      of affected individuals. The molecular underpinnings of these events are not well
      understood. To better define the molecular consequences of prion infections, we
      analyzed the transcriptional response to persistent prion infection in a panel of
      three murine neural cell lines in vitro. Colony spot immunochemistry assays
      indicated that 65-100% of cells were infected in each line. Only the Nav1 gene
      was marginally modulated in one cell line, whereas transcripts previously
      reported to be derailed in prion-infected cells were not confirmed in the present
      study. We attribute these discrepancies to the experimental stringency of the
      current study, which was performed under conditions designed to minimize
      potential genetic drifts. These findings are at striking variance with gene
      expression studies performed on whole brains upon prion infections in vivo,
      suggesting that many of the latter changes represent secondary reactions to
      infection. We conclude that, surprisingly, there are no universal transcriptional
      changes induced by prion infection of neural cells in vitro.

PMID- 18082766
TI  - Trapping of a transcription complex using a new nucleotide analogue: AMP
      aluminium fluoride.
AB  - Mechanochemical proteins rely on ATP hydrolysis to establish the different
      functional states required for their biological output. Studying the transient
      functional intermediate states these proteins adopt as they progress through the
      ATP hydrolysis cycle is key to understanding the molecular basis of their
      mechanism. Many of these intermediates have been successfully 'trapped' and
      functionally characterised using ATP analogues. Here, we present a new nucleotide
      analogue, AMP-AlF(x), which traps PspF, a bacterial enhancer binding protein, in
      a stable complex with the sigma(54)-RNA polymerase holoenzyme. The crystal
      structure of AMP-AlF(x)*PspF(1-275) provides new information on protein
      nucleotide interactions and suggests that the beta and gamma phosphates are more
      important than the alpha phosphate in terms of sensing nucleotide bound states.
      In addition, functional data obtained with AMP-AlF(x) establish distinct roles
      for the conserved catalytic AAA(+) (ATPases associated with various cellular
      activities) residues, suggesting that AMP-AlF(x) is a powerful new tool to study
      AAA(+) protein family members and, more generally, Walker motif ATPases.

PMID- 18082767
TI  - Structural role of bacterioruberin in the trimeric structure of archaerhodopsin
      2.
AB  - Archaerhodopsin-2 (aR2), a retinal protein-carotenoid complex found in the claret
      membrane of Halorubrum sp. aus-2, functions as a light-driven proton pump. In
      this study, the membrane fusion method was utilized to prepare trigonal P321
      crystals (a=b=98.2 A, c=56.2 A) and hexagonal P6(3) crystals (a=b=108.8 A,
      c=220.7 A). The trigonal crystal is made up of stacked membranes in which the aR2
      trimers are arranged on a honeycomb lattice. Similar membranous structures are
      found in the hexagonal crystal, but four membrane layers with different
      orientations are contained in the unit cell. In these crystals, the carotenoid
      bacterioruberin [5,32-bis(2-hydroxypropan-2-yl)-2,8,12,16,21,25,29,35
      octamethylhexatriaconta-6,8,10,12,14,16,18,20,22,24,26,28,30-tridecaene-2,35
      diol] binds to crevices between the subunits of the trimer. Its polyene chain is
      inclined from the membrane normal by an angle of about 20 degrees and, on the
      cytoplasmic side, it is surrounded by helices AB and DE of neighbouring subunits.
      This peculiar binding mode suggests that bacterioruberin plays a striking
      structural role for the trimerization of aR2. When compared with the aR2
      structure in another crystal form containing no bacterioruberin, the proton
      release channel takes a more closed conformation in the P321 or P6(3) crystal;
      i.e., the native conformation of protein is stabilized in the trimeric protein
      bacterioruberin complex. Interestingly, most residues participating in the
      trimerization are not conserved in bacteriorhodopsin, a homologous protein
      capable of forming a trimeric structure in the absence of bacterioruberin.
      Despite a large alteration in the amino acid sequence, the shape of the
      intratrimer hydrophobic space filled by lipids is highly conserved between aR2
      and bacteriorhodopsin. Since a transmembrane helix facing this space undergoes a
      large conformational change during the proton pumping cycle, it is feasible that
      trimerization is an important strategy to capture special lipid components that
      are relevant to the protein activity.

PMID- 18082769
TI  - Microvessel damage may play an important role in tumoricidal effect for murine
      h(22) hepatoma cells with hyperthermia in vivo.
AB  - BACKGROUND: In the present study, murine H(22) hepatoma cells were provided
      hyperthermia with different thermal dose in vitro and in vivo, thereafter we
      investigated the apoptosis, necrosis rates, and intratumoral microvessel density
      (MVD) to determine that microvessel damage plays an important role in the
      tumoricidal effect of hyperthermia. METHODS: H(22) hepatoma cells were inoculated
      in the right hind legs of mice with immunosuppression. Local hyperthermia was
      administered to these mice for 15, 30, and 45 min, respectively. After
      hyperthermia, some mice with heat treatment of 30 min were killed at 3, 6, 12,
      24, 48, 72, and 96 h after operation and others were immediately sacrificed. All
      tumor tissues were removed. They were analyzed for the death rate of tumor cells
      by flow cytometer (FCM) and observed MVD by immunohistochemistry. H(22) hepatoma
      cells in vitro were also given hyperthermia for 15, 30, and 45 min, respectively,
      and analyzed for the death rate by FCM. RESULTS: Most of the dead cells were
      apoptotic cells in the initiation phase of hyperthermia, then the necrosis rates
      rose gradually. The difference of death rates between in vivo and in vitro was
      significant for hyperthermia for 15 min, 30 min, and 45 min (P < 0.05). A strong
      positive linear correlation (r = -0.879) was observed between the death rate of
      tumor cells and MVD. CONCLUSION: Our study has shown that microvessel damage may
      play an important role in tumoricidal effect of hyperthermia.

PMID- 18082768
TI  - AKAP18 contains a phosphoesterase domain that binds AMP.
AB  - Protein kinase A anchoring proteins (AKAPs), defined by their capacity to target
      the cAMP-dependent protein kinase to distinct subcellular locations, function as
      molecular scaffolds mediating the assembly of multicomponent complexes to
      integrate and organise multiple signalling events. Despite their central
      importance in regulating cellular processes, little is known regarding their
      diverse structures and molecular mechanisms. Here, using bioinformatics and X-ray
      crystallography, we define a central domain of AKAP18 delta (AKAP18(CD)) as a
      member of the 2H phosphoesterase family. The domain features two conserved His-x
      Thr motifs positioned at the base of a groove located between two lobes related
      by pseudo 2-fold symmetry. Nucleotide co-crystallisation screening revealed that
      this groove binds specifically to adenosine 5'-monophosphate (5'AMP) and cytosine
      5'-monophosphate (5'CMP), with the affinity constant for AMP in the physiological
      concentration range. This is the first example of an AKAP capable of binding a
      small molecule. Our data generate two functional hypotheses for the AKAP18
      central domain. It may act as a phosphoesterase, although we did not identify a
      substrate, or as an AMP sensor with the potential to couple intracellular AMP
      levels to PKA signalling events.

PMID- 18082770
TI  - Research of PDGF-BB gel on the wound healing of diabetic rats and its
      pharmacodynamics.
AB  - BACKGROUND: One of the leading causes of impaired wound healing is diabetes
      mellitus. In diabetic patients, a minor skin wound often leads to serious
      complications. Many experiments had demonstrated that the expression of platelet
      derived growth factor (PDGF) and its receptor was decreased in wounds of healing
      impaired diabetic mice, indicating that a certain expression level of PDGF is
      essential for normal repair. MATERIALS AND METHODS: The diabetic rats was induced
      by a single i.p. injection of streptozotocin and a 1.8 cm diameter full-thickness
      wound was made on each side of the rat mid-back. Then the rats were randomly
      divided into five groups, with eight animals in each group as follows: blank
      control, vehicle control, 3.5 microg PDGF-BB/cm(2) treatment group, 7 microg PDGF
      BB/cm(2) treatment group and 14 microg PDGF-BB/cm(2) treatment group for either 7
      or 14 consecutive days after wounding. Re-epithelialization area was measured by
      computerized planimetry, percentage wound closure and percentage wound
      contraction was calculated, granulation tissue and collagen formation was
      assessed by Masson trichrome, cell proliferation (proliferating cell nuclear
      antigen staining) and angiogenesis (Factor VIII related antigen staining) was
      assessed by immunohistological methods. RESULTS: PDGF-BB treatment improved
      healing quality, enhanced angiogenesis, cell proliferation and epithelialization,
      and formed thicker and more highly organized collagen fiber deposition in full
      thickness excisional wound of diabetic rats. The effects of topically applied
      PDGF-BB were dose-dependent. CONCLUSIONS: PDGF-BB is an important future clinical
      tool, particularly for stimulating soft tissue repair in patients with an
      impaired capacity for wound healing.

PMID- 18082771
TI  - Induction and repair rate of DNA damage: a unified model for describing effects
      of external and internal irradiation and contamination with heavy metals.
AB  - DNA is a key-target for genotoxic stress. Hence, the knowledge of induction and
      repair rate of DNA damage are crucial to describe and predict the impact of
      stress situations. Unfortunately, DNA damage induction and repair rates are
      generally assessed separately whereas they act either concomitantly or
      transiently in living organisms. Furthermore, the interplay of induction and
      repair raises the question whether DNA repair adapts to respond to different
      amounts of DNA damage. In a previous report, we proposed a stochastic
      interpretation of the repair rate of the major radiation-induced DNA damage. We
      provided evidence that the repair rate of individual DNA damage is time
      independent whereas that of a population of DNA damage is time-dependent (Foray,
      N., Charvet, A.-M., Duchemin, D., Favaudon, V., Lavalette, D., 2005. The repair
      rate of radiation-induced DNA damage: a stochastic interpretation based on the
      gamma function. J. Theor. Biol. 236, 448-458). Here, to better describe
      situations in which DNA damage induction and repair occur together, our
      biostatistical model was modified by the introduction of a DNA damage induction
      parameter. Theoretical and experimental data were compared and discussed by
      taking concrete experimental situations: X-rays irradiation at different dose
      rates, internal irradiation with radioactive compound, contamination with heavy
      metal and detection of DNA damage by immunofluorescence. By assuming that DNA
      repair rate is invariant whatever the amount of DNA damage, our model provides
      good prediction of experimental data suggesting its relevance for the description
      of complex situations of co-toxicities.

PMID- 18082772
TI  - BDI-modelling of complex intracellular dynamics.
AB  - A BDI-based continuous-time modelling approach for intracellular dynamics is
      presented. It is shown how temporalized BDI-models make it possible to model
      intracellular biochemical processes as decision processes. By abstracting from
      some of the details of the biochemical pathways, the model achieves understanding
      in nearly intuitive terms, without losing veracity: classical intentional state
      properties such as beliefs, desires and intentions are founded in reality through
      precise biochemical relations. In an extensive example, the complex regulation of
      Escherichia coli vis-a-vis lactose, glucose and oxygen is simulated as a discrete
      state, continuous-time temporal decision manager. Thus a bridge is introduced
      between two different scientific areas: the area of BDI-modelling and the area of
      intracellular dynamics.

PMID- 18082773
TI  - Twelve-lead electrocardiogram monitoring of subjects before and after voluntary
      exposure to the Taser X26.
AB  - OBJECTIVES: The Taser (Taser International, Scottsdale, Ariz) uses high-voltage
      electricity to incapacitate subjects. We sought to evaluate cardiac rhythm
      changes during deployment of the Taser on healthy volunteers. METHODS: This
      prospective study was performed on 32 healthy volunteer subjects receiving a
      Taser X26 discharge. The subjects had baseline 12-lead electrocardiogram (ECG)
      monitoring performed immediately before and within 1 minute after the Taser
      discharge. Changes in cardiac rhythm, morphology, and interval duration were
      evaluated. Descriptive statistics and paired-sample t test comparisons are
      reported. RESULTS: All 32 subjects had an interpretable 12-lead ECG obtained
      before and after the Taser activation, although 1 subject's post-PR interval
      could not be determined. The mean age and body mass index were 33 years and 26.5
      kg/m2, respectively. Overall, there was a significant increase in heart rate
      (2.4; 95% confidence interval [CI], 0.0-4.9) and a decrease in PR interval (-6.5;
      95% CI, -9.7 to -3.3). When stratified by sex, only the PR interval in men
      significantly decreased (-5.9; 95% CI, -9.2 to -2.5). There were significant
      changes in heart rate (4.0; 95% CI, 1.3-6.7), PR interval (-6.0; 95% CI, -11.3 to
      -0.7), and QT interval (-18.8; 95% CI, -33.2 to -4.3) among those with a normal
      body mass index, and in PR interval among those who were overweight/obese (-6.7;
      95% CI, -10.8 to -2.5). None of the statistically significant differences between
      ECG measures were clinically relevant. CONCLUSIONS: There were no cardiac
      dysrhythmia and interval or morphology changes in subjects who received a Taser
      discharge based on a 12-lead ECG performed immediately before and within 1 minute
      after a Taser activation.

PMID- 18082774
TI  - Authorship, collaboration, and predictors of extramural funding in the emergency
      medicine literature.
AB  - OBJECTIVES: The objectives of the study were to examine the last decade of
      general emergency medicine (EM) literature published in the United States for
      trends with regard to authorship and multidisciplinary collaboration and to
      estimate the effect on extramural funding. METHODS: Print articles published in
      the Academic Emergency Medicine, Annals of Emergency Medicine, Journal of
      Emergency Medicine, and American Journal of Emergency Medicine between 1994 and
      2003 were reviewed. Original research, case reports/series, and others
      (consensus/educational) were considered; abstracts, book reviews, and editorials
      were not. The author byline was reviewed for number, specialty, nationality,
      collaboration, and presence of extramural funding. Multidisciplinary
      collaboration was defined as authors from 2 or more specialties, whereas multi
      institutional collaboration was defined as EM authors from more than one
      institution. Logistic regression was used to identify predictors of extramural
      funding from the variables collected. RESULTS: Of 5728 articles identified, there
      were 3278 (57%) original research, 1437 (25%) case reports/series, and 975 (17%)
      classified as others. The percentage funded was 22% for all articles (32% for
      original research). The literature had at least one EM investigator as coauthor
      84% of the time. Article location of origin was the United States (63%), foreign
      (15%), and combined (22%). Multidisciplinary collaboration increased overall from
      33% in 1994 to a high of 43% in 2003. Multi-institutional collaboration also
      increased from 16% in 1994 to 26% in 2003. The percentage of articles having 6 or
      more authors increased from 12% to 18% over the decade. Of all variables studied,
      only article type (original research: odds ratio, 4.8; 95% confidence interval,
      4.0-5.6) and foreign source (non-United States: odds ratio, 1.3; 95% confidence
      interval, 1.1-1.5) predicted extramural funding. CONCLUSIONS: The number of
      authors per article in the EM literature has steadily increased over the last
      decade, as has evidence of collaboration with other specialties. This increase in
      collaboration and author number has not been associated with increased extramural
      funding in the general EM literature published in the United States.

PMID- 18082775
TI  - Electrocardiographic algorithms for predicting the complexity of coronary artery
      lesions in ST-segment elevation myocardial infarction in ED.
AB  - OBJECTIVE: In reperfusion strategy for ST-elevation myocardial infarction
      (STEMI), emergency surgical bypass grafting might be considered for patients with
      significant multivessel coronary diseases complicated by cardiogenic shock. The
      culprit lesions in STEMI can be predicted from electrocardiographic (ECG)
      findings. However, whether the complexity of coronary artery lesions in STEMI can
      be predicted from characteristic ECG findings remained unclear. MATERIALS AND
      METHODS: The initial 12-lead ECG parameters in each lead recording from patients
      with STEMI receiving primary percutaneous coronary intervention within 12 hours
      were retrospectively analyzed. A sequential ECG algorithm was developed to
      predict the complexity of coronary artery lesions. RESULTS: In patients with
      inferior wall STEMI, the presence of the following 2-step criteria indicated 3
      vessel disease (3VD), with a sensitivity of 92.1% and a specificity of 81.8%: (1)
      ST depression or flat T wave in leads V5 or V6; and (2) ST elevation of more than
      2 mm in at least 1 of II, III, aVF, or Q (loss of septal r) without ST elevation
      in aVR. In patients with anterior wall STEMI, the following criteria indicated
      3VD: (1) ST elevation of more than 4 mm in at least 1 of the precordial leads and
      combined with QRS interval of more than 120 ms; then (2) a flat T wave over aVR,
      or aVL combined with flat T wave ST depression over lead I or Q wave over all
      leads II, III, and aVF. This algorithm detects patients with 3VD with a
      sensitivity of 76.5% and a specificity of 100%. However, when the whole algorithm
      is completed, the sensitivity can reach up to 88.4% and the specificity can still
      be 100%. CONCLUSION: By using this ECG algorithm, 3VD might be distinguished
      early from single-vessel disease in patients with STEMI for appropriate
      reperfusion strategy.

PMID- 18082776
TI  - Volumetric bladder ultrasound performed by trained nurses increases
      catheterization success in pediatric patients.
AB  - OBJECTIVE: The objective of the study was to determine whether the use of
      volumetric ultrasound by trained pediatric emergency department (ED) nurses
      improves first-attempt urine collection success rates. METHODS: This randomized
      controlled trial was conducted in children aged < or = 36 months requiring
      diagnostic urine samples. Children were randomized to either the conventional
      (nonimaged) or the ultrasound arm. Demographics, number of catheterizations
      required for success, postponements, and collection times were recorded. RESULTS:
      Forty-five children were assigned to the conventional and 48 to the ultrasound
      arm (n = 93). First-attempt success rates were higher in the ultrasound arm: 67%
      (conventional) vs 92% (ultrasound) (P = .003). Both urinalysis and culture were
      less likely to be completed on conventional group specimens (91% vs 100%; P =
      .04). However, mean conventional group urine collection time was less than the
      ultrasound group's collection time (12 vs 28 minutes; P < .001). CONCLUSIONS:
      Although there is a time delay, urine collection in the ultrasound arm generated
      a significant improvement over conventional catheterization in obtaining an
      adequate urine sample.

PMID- 18082777
TI  - Acid-base interpretation can be the predictor of outcome among patients with
      acute organophosphate poisoning before hospitalization.
AB  - OBJECTIVES: Acute organophosphate (OP) poisoning causing alteration in acid-base
      equilibrium was reported before. Hence, different acid-base statuses may present
      in patients with acute poisoning due to OP exposure. This study aims to determine
      the impact of acid-base interpretation in patients with acute OP poisoning before
      hospitalization in medical care units and to describe the pattern of mortality
      with different acid-base statuses. DESIGN AND PATIENTS: Over a 9-year
      retrospective study, from July 1996 to August 2005, a total of 82 consecutive
      patients with acute OP poisoning were admitted to the China Medical University
      Hospital (Taichung, Taiwan) within 24 hours after exposure to OP and were
      enrolled into this study. RESULTS: Patients with acute OP poisoning were divided
      into 4 groups: without acidosis, metabolic acidosis, respiratory acidosis, and
      mixed acidosis. Overall survival (Kaplan-Meier curves) among groups was
      statistically significant (P < .0001). The mortality rate of acute OP poisoned
      patients with metabolic acidosis was 25%, and 75% of those patients died of
      cardiovascular failure. The mortality rate of acute OP poisoning with respiratory
      acidosis was 50%, and 50% of those patients died of respiratory failure.
      CONCLUSIONS: Acid-base interpretation can be effective in quick diagnosis and
      prediction of the outcome of patients with acute OP poisoning (without acidosis <
      metabolic acidosis < respiratory acidosis < mixed acidosis) before
      hospitalization. Major causes of death are different between the respiratory
      acidosis and metabolic acidosis groups of patients with acute OP poisoning.

PMID- 18082778
TI  - Does intraosseous equal intravenous? A pharmacokinetic study.
AB  - STUDY OBJECTIVE: Despite the growing popularity of intraosseous infusion for
      adults in emergency medicine, to date there has been little research on the
      pharmacokinetics of intraosseously administered medications in humans. The
      objective of the study was to compare the pharmacokinetics of intraosseous vs
      intravenous administration of morphine sulfate in adults. METHODS: The study
      followed a prospective, randomized, crossover design. Each subject was equipped
      with an indwelling intraosseous access device and an intravenous line. Subjects
      were randomized to receive a 5-mg bolus of morphine sulfate infused
      intraosseously or intravenously, followed by the alternate administration route
      24 hours later. Serial venous blood samples (5 mL) were taken at baseline and at
      13 time points over 8 hours postinfusion. Blood samples were analyzed for
      morphine concentration by radioimmunoassay. Pharmacokinetic parameters were
      calculated from the data, including maximum plasma concentration (Cmax), time to
      maximum concentration (Tmax), and area under plasma concentration-time curve
      (AUC), among others. Data were analyzed by analysis of variance. RESULTS: No
      statistically significant differences were observed between intraosseous and
      intravenous administration of morphine sulfate for nearly all of the
      pharmacokinetic parameters including Cmax (235 +/- 107 vs 289 +/- 197 ng/mL, mean
      +/- SD, i.o. vs i.v., respectively), Tmax (1.3 +/- 0.5 vs 1.4 +/- 0.5 minutes),
      and AUC(0-infinity) (4372 +/- 1785 vs 4410 +/- 1930 ng min(-1) mL(-1)). There
      was, however, a statistically significant difference in the volume of
      distribution in the central compartment, V(d) (P = .0247), which in the opinion
      of the investigators was thought to be due to a minor deposition effect near the
      intraosseous port or in the bone marrow. CONCLUSION: The results support the
      bioequivalence of intraosseous and intravenous administration of morphine sulfate
      in adults.

PMID- 18082779
TI  - Appendicitis outcomes with increasing computed tomographic scanning.
AB  - PURPOSE: The purpose of the study was to examine appendicitis outcomes over time
      as computed tomographic (CT) scanning was incorporated into practice. BASIC
      PROCEDURES: Using chart review, appendectomy cases from 1998 to 2004 were
      analyzed by year for CT scanning rate, delay in treatment, complications,
      negative appendectomies, and time to surgery. Delay in treatment was defined as
      discharge from the ED at first visit or more than 20 hours from examination until
      surgery. MAIN FINDINGS: Computed tomographic scanning increased from 12.3% in
      1998 to 84.4% in 2004. Delay in treatment decreased from 7.8% in 1998 to 3.0% in
      2004. Complications decreased from 33.3% in 1998 to 21.3% in 2004. Negative
      appendectomy rate did not change significantly over time. There was a slight
      decrease that may have resulted from chances, variation (p=.087) for the line
      trend. Median time to surgery increased from 250 minutes in 1998 to 426 minutes
      in 2002, decreasing to 370 minutes by 2004. CONCLUSION: During the period when CT
      scanning increased dramatically, delays in treatment and complications decreased
      significantly, but negative appendectomy rates decreased only slightly, if at
      all. Median time to surgery increased.

PMID- 18082780
TI  - The effects of prostaglandin inhibition on whole-body ischemia-reperfusion in
      swine.
AB  - BACKGROUND: Prostaglandins (PGs), particularly PGE2 and PGI2, have a salutary
      effect on myocardial ischemia-reperfusion-induced myocardial damage. OBJECTIVE:
      We investigated acute PG synthesis inhibition on outcomes from whole-body
      ischemia-reperfusion injury using a well-characterized model of ventricular
      fibrillation (VF)-induced cardiac arrest in pigs. In addition, we assessed early
      postresuscitation myocardial function in survivors using echocardiography as well
      as a biochemical measure of myocardial tissue damage. METHODS: Twenty-six animals
      (weight range, 25-35 kg) received indomethacin (INDO; 2 mg/kg, nonselective
      cyclooxygenase (COX) 1 and 2 inhibitor), celecoxib (2 mg/kg; selective COX-2
      inhibitor [COX-2-I]), or saline placebo 30 minutes before induction of VF. After
      3 minutes of VF with no intervention, the animals received standard chest
      compression using an automated chest compression device (Thumper; Michigan
      Instruments, Grand Rapids, Mich) for 15 minutes. After 18 minutes of VF, a single
      dose of vasopressin and bicarbonate were administered and defibrillation
      attempted. Hemodynamics, regional blood flow, echocardiography, and serum
      troponin I measurements were performed before and after drug infusion or placebo,
      during cardiopulmonary resuscitation (CPR), and after return of spontaneous
      circulation (ROSC). RESULT: Return of spontaneous circulation to 180 minutes
      occurred in 9 of 10 animals receiving placebo, 7 of 8 animals given COX-2-I, and
      3 of 8 animals given INDO (P = .01, placebo or COX-2-I vs INDO). Hemodynamics did
      not differ among groups over time. Indomethacin and COX-2-I attenuated the
      increase in regional blood flow in the heart and brain, observed in the placebo
      group, 30 minutes after ROSC. All 3 study groups had significant decrease in
      percentage of ejection fraction and fractional shortening after ROSC and
      significant increase in wall motion score index after ROSC. In the COX-2-I group,
      troponin I increased 9-fold compared with placebo, 180 minutes after ROSC. Whole
      body ischemia-reperfusion and CPR significantly increased PGE2 and PGI2 levels.
      The latter were blunted by pretreatment with COX inhibition. CONCLUSION: These
      findings suggest that PGs have a critical role in myocardial function and
      viability during low-blood-flow states produced by CPR and possibly other low
      blood-flow clinical conditions.

PMID- 18082781
TI  - Superoxide dismutase activity and malondialdehyde level in plasma and
      morphological evaluation of acute severe hemorrhagic shock in rats.
AB  - OBJECTIVES: The aim of the study was to investigate the changes of the activity
      of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in plasma
      and organ damage during the acute severe hemorrhagic shock (ASHS), as well as to
      analyze their relationship. METHODS: Twenty male Wistar rats (230-270 g) were
      randomly divided into sham hemorrhage shock (SHS) group and ASHS group. Acute
      severe hemorrhagic shock rats were induced by drawing blood through a femoral
      arterial catheter for 15 minutes with the final mean arterial blood pressure
      decreased to 35 to 40 mm Hg. The animals were killed after the mean arterial
      blood pressure was maintained at this level for 1 hour. The activity of SOD and
      the level of MDA in plasma were measured, and pathologic changes of the major
      organs (heart, liver, spleen, lung, kidney, and brain) were observed by
      microscopy. RESULTS: The SOD activities and MDA levels in the ASHS group both
      increased continuously during the whole experiment. The SOD activities and MDA
      levels in plasma were not significantly different between the prehemorrhagic
      stage of ASHS and that of SHS (P > .05). The SOD activities and MDA levels were
      significantly higher in the ASHS initial stage than in the prehemorrhagic stage
      (P < .01). Compared with the ASHS initial stage, there was a significant (P <
      .01) increase in SOD activities and MDA levels in the ASHS end stage. Severe
      microscopic injuries appeared in the major organs (heart, liver, spleen, lung,
      kidney, and brain) of ASHS rats. CONCLUSION: The changes of the activity of SOD
      and the level of MDA in ASHS may have a positive correlation.

PMID- 18082782
TI  - Analgesic pretreatment for antibiotic skin test: vapocoolant spray vs ice cube.
AB  - OBJECTIVES: The objective of this study was to compare the efficacy of ethyl
      chloride spray and ice cube for the control of pain induced by the antibiotic
      skin test. METHODS: We performed a prospective, crossover, randomized study in
      which healthy adult volunteers received an intradermal skin test on both arms
      after different analgesic pretreatments. We assessed the pretreatment pain and
      discomfort after the intradermal skin injection using a 100-mm visual analogue
      scale. RESULTS: A total of 50 volunteers were enrolled in the study. The mean
      pain scores after the skin test were 32.4 +/- 17.6 and 54.7 +/- 22.4 mm, for the
      ice cube and vapocoolant spray pretreatment, respectively (P < .0001). The mean
      discomfort scores during pretreatment were 20.0 +/- 15.2 mm for ice cube and 10.5
      +/- 11.5 mm for vapocoolant spray (P < .0001). Forty-five (90%) subjects
      preferred the ice cube pretreatment for the intradermal skin test. CONCLUSIONS:
      The ice cube application was significantly more effective than the vapocoolant
      spray in reducing the pain of the antibiotic skin test. Hence, the ice cube
      pretreatment is suggested for easy and fast pain reduction for the antibiotic
      skin test in the emergency department.

PMID- 18082783
TI  - Impact of patient and environmental factors on capillary refill time in adults.
AB  - OBJECTIVES: Capillary refill time (CRT) has been taught as a rapid indicator of
      circulatory status. The aim of this study was to define normal CRT in the
      Australian context and the environmental, patient, and drug factors that
      influence it. METHODS: This prospective observational study included healthy
      adults at hospital clinics, workplaces, universities, and community groups.
      Volunteer participants provided their age, sex, ethnic group, and use of
      hypertensive or cardiac medications. Capillary refill time, ambient temperature,
      and patient temperature were recorded in a standard manner. Data were analyzed
      using descriptive statistics and regression analyses. The 95th percentile was
      used to define the upper limit of normal. RESULTS: One thousand participants were
      included; 57% were women, 90% were white, and 21% were taking cardiac
      medications. The median CRT was 1.9 seconds (95th percentile, 3.5 seconds). The
      CRT increased 3.3% for each additional decade of age. The CRT was also on average
      7% lower in men than in women. The CRT decreased by 1.2% per degree-Celsius rise
      of ambient temperature, independently of patient's temperature, and decreased by
      5% for each degree-Celsius rise in patient temperature, independently of ambient
      temperature. On multivariant analysis, age, sex, ambient temperature, and patient
      temperature were statistically significant predictors of CRT, but together
      explain only 8% of the observed variability. CONCLUSION: Capillary refill time
      varies with environmental and patient factors, but these account for only a small
      proportion of the variability observed. Its suitability as a reliable clinical
      test is doubtful.

PMID- 18082784
TI  - ED management of pediatric syncope: searching for a rationale.
AB  - OBJECTIVE: The aim of this study was to evaluate emergency department (ED)
      management of childhood syncope, focusing on diagnostic tests ordered, whether a
      reason for specific testing was recorded, and hospital admission rates. METHODS:
      We reviewed ED records of patients aged 5 to 20 years who presented to a
      community hospital ED with syncope or near-syncope over a 1-year period (April 1,
      2004, to March 31, 2005). Patient charts were nonelectronic (paper). We reviewed
      the elements of the recorded history and physical examination for each patient.
      The specific tests ordered in the ED were classified into 3 general testing
      categories for each patient as follows: (1) simple testing, with a hospital
      charge of $100 or less per test; (2) expanded testing, more than $100 per test,
      with a recorded explanation; and (3) expanded testing without a recorded
      explanation. RESULTS: The charts of 140 patients were reviewed. Of these, we
      excluded 27 based on exclusion criteria, including history of neurologic
      disorders. The mean age of the remaining 113 patients was 14.8 +/- 3.3 years.
      Most (80%) presented with syncope; 20% had near-syncope. Ten percent were
      admitted to the hospital, over half for an electrocardiogram (ECG) interpreted as
      abnormal by an ECG machine and/or the ED staff. Overall, 17.5% of patients had
      simple testing, 32.5% had expanded testing with explanation, and 50% had expanded
      testing without explanation. Patients with syncope were more likely than patients
      with near-syncope to be in the expanded testing category (P < .008). The most
      commonly ordered tests in the ED in order of decreasing frequency were
      electrolytes (90%), ECG (85%), complete blood count (80%), urinalysis, urinary
      drug screen, or urinary human chorionic gonadotropin (76%), head computed
      tomography (CT, 58%), and chest x-ray (37%). The most expensive of these tests
      was the head CT; all head CT results were negative. CONCLUSIONS: A relatively
      high number of our subjects were admitted (10%), most often because of questions
      raised by the ECG. Although an ECG is widely recommended for pediatric syncope
      presenting to the ED, this suggests that ECG interpretation by a pediatric
      cardiologist would be helpful before the decision to admit is made. In addition,
      58% of our subjects had a head CT in the ED; all CT results were negative. This
      high percentage of head CTs for pediatric syncope has not been previously
      reported.

PMID- 18082785
TI  - Health care facility-based decontamination of victims exposed to chemical,
      biological, and radiological materials.
AB  - Since the US terrorist attacks of September 11, 2001, concern regarding use of
      chemical, biological, or radiological weapons is heightened. Many victims of such
      an attack would present directly to health care facilities without first
      undergoing field decontamination. This article reviews basic tenets and
      recommendations for health care facility-based decontamination, including
      regulatory concerns, types of contaminants, comprehensive decontamination
      procedures (including crowd control, triage, removal of contaminated garments,
      cleaning of body contaminants, and management of contaminated materials and
      equipment), and a discussion of methods to achieve preparedness.

PMID- 18082786
TI  - ED endovaginal pelvic ultrasound in nonpregnant women with right lower quadrant
      pain.
AB  - INTRODUCTION: We hypothesized that emergency physician-performed endovaginal
      ultrasound (EVUS) would change diagnostic decision making in nonpregnant women
      with right lower quadrant (RLQ) pain. METHODS: A prospective cohort of female
      patients was enrolled at an urban emergency department (ED). Inclusion criteria
      were RLQ pain, hemodynamic stability, and a strong suspicion for appendicitis or
      right adnexal pathology. Treating physicians were queried regarding pre- and post
      ED EVUS probability of disease, differential diagnoses, consultation, and
      management. Positive findings included large cysts or multitissue densities,
      tubal dilation, uterine enlargement/mass, and extensive peritoneal fluid.
      RESULTS: With a positive ED EVUS, mean physician probability increased for
      gynecologic (24%) and decreased for both surgical (14%) and medical (20%)
      disease. With a negative ED EVUS, mean physician probability increased for
      surgical disease (5.3%) and decreased for gynecologic disease (18.6%).
      CONCLUSION: Emergency department EVUS changes physician diagnostic decision
      making in nonpregnant women with undifferentiated RLQ pain.

PMID- 18082787
TI  - Internal hernia associated with Meckel's diverticulum in 2 pediatric patients.
AB  - We report 2 pediatric cases of small bowel obstruction due to a Meckel's
      diverticulum complicated with internal hernia. Abdominal multidetector computed
      tomograms with multiple planar reconstructions revealed a bridge-like lesion with
      inconspicuous mucosal folds in the right lower quadrant formed by adhesion of the
      tip of Meckel's diverticulum with the adjacent mesentery, with ileal loops
      converging at the "bridge" and engorged mesenteric vessels. These 2 cases
      highlight the feasibility of multidetector computed tomography, especially in the
      ED, in revealing this unusual etiology of small bowel obstruction.

PMID- 18082788
TI  - Management of ST-segment elevation myocardial infarction in EDs.
AB  - Emergency department (ED) physicians are critical in the accurate diagnosis,
      efficient management, and treatment of patients with ST-segment elevation
      myocardial infarction. The initial reperfusion strategy involves the choice
      between mechanical reperfusion using primary percutaneous coronary intervention
      and pharmacologic treatment with fibrinolytics. The benefits of these approaches
      are time dependent, and practices vary according to institutional resources and
      local guidelines. Nevertheless, the need for early intervention and the use of
      certain therapies are well recognized. Therefore, ED physicians must be aware of
      all treatment options available, including the use of adjunctive therapies.
      Initial treatment should include beta-blockers, aspirin (or clopidogrel if
      aspirin is contraindicated), nitroglycerin, and analgesia, regardless of
      reperfusion strategy. Clopidogrel is now approved as an adjunctive therapy for
      patients undergoing fibrinolysis as their reperfusion therapy. Both
      unfractionated heparin and low-molecular-weight heparin are feasible adjunctives
      in patients with ST-segment elevation myocardial infarction undergoing
      reperfusion therapy. In addition, multiple new antithrombin agents are being
      investigated. The choice adjunctive treatments should be based on specific
      patient populations and on the initial reperfusion strategy.

PMID- 18082789
TI  - Prostaglandin inhibition and ischemia: where are the data?

PMID- 18082790
TI  - Quantitative human chorionic gonadotropin measurement in urine using the Access
      immunoassay.

PMID- 18082791
TI  - Beta-agonists for patients with chronic obstructive pulmonary disease and heart
      disease?

PMID- 18082792
TI  - The number of criminal prosecutions against physicians due to medical negligence
      is on the rise in Japan.

PMID- 18082793
TI  - Specific electrocardiographic features in arrhythmogenic right ventricular
      cardiomyopathy.

PMID- 18082794
TI  - Clinical presentation of non-ST-segment elevation myocardial infarction in the
      course of intoxication with mad honey.

PMID- 18082795
TI  - Posterior dislocation of the clavicle at the sternoclavicular joint.

PMID- 18082796
TI  - Spontaneous splenic rupture caused by splenic peliosis of a hemodialysis patient
      with chronic renal failure receiving erythropoietin.

PMID- 18082797
TI  - Massive parastomal hernia with strangulation.

PMID- 18082798
TI  - Complete aortic occlusion caused by cardiac myxoma emboli.

PMID- 18082799
TI  - Massive valproic acid overdose, a misleading case.

PMID- 18082800
TI  - An unusual case of acute dyspnea.

PMID- 18082801
TI  - Air bag and oral anticoagulation: a deadly combination in a low-velocity car
      accident.

PMID- 18082802
TI  - Painless type A aortic dissection hiding in bigeminal premature ventricular
      contractions.

PMID- 18082803
TI  - Amantadine-induced serotonin syndrome in a patient with renal failure.

PMID- 18082804
TI  - A case report of Brugada-type electrocardiographic changes in a patient taking
      lithium.

PMID- 18082805
TI  - Should naloxone be prescribed in the ED management of patients with cardiac
      arrest? A case report and review of literature.

PMID- 18082806
TI  - Laryngeal sarcoidosis causing acute upper airway obstruction.

PMID- 18082807
TI  - An unusual cause of small bowel obstruction in the ED.

PMID- 18082809
TI  - Ovarian hyperstimulation syndrome: an important complication of in vitro
      fertilization.

PMID- 18082808
TI  - Posttraumatic delayed facial nerve palsy.

PMID- 18082810
TI  - Spontaneous pneumomediastinum after air travel.

PMID- 18082811
TI  - Push-ups may be hazardous to your health: an atraumatic etiology for bilateral
      shoulder dislocation.

PMID- 18082812
TI  - Splenic rupture after colonoscopy.

PMID- 18082813
TI  - Acute intoxication with terazosin.

PMID- 18082814
TI  - A patient with numerous tablets remaining in the stomach even 5 hours after
      ingestion.

PMID- 18082815
TI  - Partial agenesis of the posterior arch of the atlas.

PMID- 18082821
TI  - Re: Validation of the overactive bladder symptom score J. G. Blaivas, G.
      Panagopoulos, J. P. Weiss And C. Somaroo J Urol 2007; 178: 543-547.

PMID- 18082822
TI  - Re: Tunneled tunica vaginalis flap is an effective technique for recurrent
      urethrocutaneous fistulas following tubularized incised plate urethroplasty J. C.
      Routh, J. J. Wolpert and Y. Reinberg J Urol 2006; 176: 1578-1581.

PMID- 18082823
TI  - Re: Editorial comments: C. G. Chaussy and A. Blana, J Urol 2007; 178: 2369-2371.

PMID- 18082824
TI  - Re: Standard versus limited pelvic lymph node dissection for prostate cancer in
      patients with a predicted probability of nodal metastasis greater than 1% K.
      Touijer, F. Rabbani, J. R. Otero, F. P. Secin, J. A. Eastham, P. T. Scardino And
      B. Guillonneau J Urol 2007; 178: 120-124.

PMID- 18082825
TI  - Re: Patterns of recurrence and outcomes following induction bacillus Calmette
      Guerin for high risk Ta, T1 bladder cancer s. P. Lerner, C. M. Tangen, H.
      Sucharew, D. Wood and E. D. Crawford J Urol 2007; 177: 1727-1731.

PMID- 18082826
TI  - Adenocarcinoma of suburethral diverticulum.

PMID- 18082827
TI  - Fibrous pseudotumor of the tunica vaginalis.

PMID- 18082828
TI  - The impact of a fellowship on resident training in an academic pediatric urology
      practice.
AB  - PURPOSE: The impact of a fellowship on resident operative experience and
      education is unclear. We sought to address this issue by comparing resident
      operative case logs and the pediatric portion of the American Urological
      Association resident inservice examination at our institution before and after
      establishing a pediatric urology fellowship in 2002. MATERIALS AND METHODS:
      Pediatric operative case logs of all urological residents from 1998 to 2006 at
      Vanderbilt University were reviewed. We recorded index and total number of cases
      as specified by the Accreditation Council for Graduate Medical Education. All
      residents had completed 6 months of pediatric urology training. Statistical
      analysis was performed using 2-sample equal variance Student t tests. We compared
      the 8 index categories and total index cases performed by residents, scores on
      the pediatric portion of the American Urological Association inservice
      examination and resident average percentiles for index cases referenced to
      national data, before and after the implementation of an Accreditation Council
      for Graduate Medical Education accredited pediatric urology fellowship. RESULTS:
      Before implementation of the pediatric urology fellowship residents performed
      significantly more hypospadias procedures, pyeloplasties, renal surgeries,
      ureteroneocystostomies and urinary/bowel diversions (p <0.05), while the total
      number of index cases performed was not significantly affected (p = 0.13). In
      contrast, after the fellowship was started residents performed more
      hydrocelectomies/hernia repairs (p = 0.01). Compared to national averages for
      index cases in 2004 to 2005, residents maintained greater than the 50th
      percentile in all categories except urinary diversion, which was between the 30th
      and 50th percentiles. Furthermore, residents were in the 70th to 90th percentile
      in 3 of 9 categories, and greater than the 90th percentile in 3, including total
      number of index cases. No statistically significant difference in the area of
      pediatric urology was observed on the resident inservice examination scores
      before and after the fellowship was established. CONCLUSIONS: Residents performed
      significantly fewer index cases in some areas following initiation of a pediatric
      urology fellowship at Vanderbilt University, although the total number of index
      cases performed by residents remained unchanged. Despite the presence of a
      fellow, residents have remained at or well above the national average in all
      index case categories except urinary diversion. Moreover, establishment of a
      fellowship did not negatively impact the educational experience as measured by
      American Urological Association resident inservice examination scores,
      specifically in the area of pediatric urology. Choosing the optimal time to
      institute a fellowship should be made with fellow and resident education as the
      utmost priority. Periodic review of the data should also be performed to maintain
      consistent, positive experiences for fellowship and residency training.

PMID- 18082829
TI  - Subclinical varicocele in the pediatric age group.
AB  - PURPOSE: This study was designed to assess the natural history of subclinical
      varicocele in the pediatric age group. MATERIALS AND METHODS: We conducted a
      school screening for varicocele in 2,107 children 10 to 16 years old, performing
      clinical examination and venous Doppler study. A total of 354 boys (16.8%)
      without clinically detectable varicocele had venous testicular reflux during a
      Valsalva maneuver. Of these children 36 (a 10% sample) were selected randomly and
      followed annually for 4 years, with assessment of testicular volume (ultrasound
      values), degree of varicocele according to the Dubin and Amelar classification,
      and Doppler findings according to the Hirsh testicular Doppler classification.
      The control group consisted of 20 children selected randomly from the same
      population, who did not have a varicocele and had a normal Doppler study.
      Fisher's exact test was used with a significance value at p <0.05. RESULTS: Mean
      age of the 36 children at the first assessment was 12.8 years (SD 1.7). Two boys
      (5.5%) had spontaneous resolution of testicular venous reflux within 2 years, and
      in 24 (67%) the subclinical varicocele did not change. The remaining 10 children
      (28%) had a clinically detectable varicocele, which was grade I in 1 patient,
      grade II in 7 and grade III in 2. Of these patients 1 had associated left
      testicular hypoplasia greater than 20%. During the 4-year period there were no
      clinically detectable varicoceles in the control group (p = 0.01). CONCLUSIONS:
      The proportion of children with subclinical varicocele progressing to a
      clinically detectable form of the condition was 28% (95% CI 14 to 45) during a 4
      year period. We suggest that children with subclinical varicocele require long
      term followup.

PMID- 18082830
TI  - Urinary sodium dodecyl sulfate electrophoresis with silver staining: a
      noninvasive diagnostic tool for obstructive uropathy in children.
AB  - PURPOSE: Obstructive uropathy such as ureteropelvic junction obstruction in the
      newborn is a major diagnostic and therapeutic dilemma. We investigated whether
      urinary sodium dodecyl sulfate electrophoresis with polyacrylamide gel
      electrophoresis with silver staining could be used to discriminate between
      children requiring and those not requiring pyeloplasty. MATERIALS AND METHODS: In
      a pilot study we analyzed the urine of 18 children (mean age 2.7 years) with
      grade III or IV hydronephrosis according to the Society for Fetal Urology
      classification. A total of 44 healthy children were studied as controls. Children
      with hydronephrosis were followed using ultrasound, (99m)technetium
      mercaptoacetyltriglycine diuretic renography and voiding cystourethrography.
      Urine was obtained by spontaneous voiding and studied by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis with silver staining using Melzer's
      modification. After the study period test results were compared to outcomes, ie
      whether patients required surgery, and to normalization of previously abnormal
      protein excretion patterns. RESULTS: All but 1 of the healthy controls had a
      normal electrophoresis assessment. Of 9 patients followed for hydronephrosis 7
      had an abnormal electrophoresis result preoperatively. One child had to be
      operated on twice because of relapse of ureteropelvic junction obstruction. Six
      children returned to a normal electrophoresis result postoperatively, including
      the child who was operated on twice. All children with an initially normal
      electrophoresis assessment displayed persistent normal values, except 1. Children
      shifting from a normal to an abnormal electrophoresis result underwent surgery
      after exclusion of urinary tract infection. CONCLUSIONS: Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis with silver staining seems to be a good
      predictive test for clinically relevant ureteropelvic junction obstruction.
      Further studies are being performed to see whether the test can stand against the
      gold standard, (99m)technetium mercaptoacetyltriglycine diuretic renography.

PMID- 18082831
TI  - New insight into surgical anatomy of epispadiac penis and its impact on repair.
AB  - PURPOSE: Surgical anatomy of the epispadiac penis is still not fully described.
      Using our complete disassembly technique, we discovered some anatomical features
      of epispadiac penis that may have significant impact on surgical outcome.
      MATERIALS AND METHODS: A total of 52 patients 2 days to 19 years old (mean age 43
      months) underwent primary repair of epispadias between October 1996 and December
      2006. After complete penile disassembly, ie full mobilization of the corporeal
      bodies, neurovascular bundles and urethral plate, reassembly of the penile
      entities was done. The urethral plate is tubularized and ventralized. The
      corporeal bodies are straightened and lengthened by 2 transverse incisions and
      grafting, joined medially and fixed to the glans cap. The glans is reconstructed,
      and the neurovascular bundles are moved dorsally and joined. The skin is
      reconstructed using different local flaps. RESULTS: Investigating the anatomical
      features of the epispadiac penis, we discovered several distinguishing features.
      The corporeal bodies are separated and triangular in shape. They represent the
      main substrate of dorsal curvature due to the significant disproportion in length
      between the long ventral and short wedge-shaped dorsal sides. The length of the
      neurovascular bundles is determined by their course-they are longer if they
      overlie the ventral side of the corpora and shorter if positioned over the dorsal
      side. The skin between the scrotum and penis has characteristics similar to
      penile skin. A good functional and esthetic outcome was achieved in 46 patients.
      Erection and glanular sensitivity were preserved in all patients. There was no
      necrosis of the glans or corporeal bodies. Complications included urethral
      fistula in 4 patients, stenosis in 2 and mild residual curvature in 2.
      CONCLUSIONS: New insights into the anatomical features of the epispadiac penis
      can have a significant impact on surgical outcomes.

PMID- 18082835
TI  - Introduction.

PMID- 18082836
TI  - A critical look at "high-risk" in choosing the proper intervention for patients
      with carotid bifurcation disease.
AB  - Refinements in the technique of carotid endarterectomy have been accompanied by a
      growing literature calling into question the notion that a broad class of
      patients is at high-risk for surgery due to clinical comorbidities. Moreover,
      progress in the percutaneous revascularization of carotid bifurcation disease has
      highlighted the need for direct comparisons between endarterectomy and stenting
      across the entire spectrum of perioperative risk. The improved safety of carotid
      stenting, to some extent due to the advent of cerebral protection devices, has
      further altered the risk-to-benefit analysis. Lastly, dramatic improvements in
      medical therapy for the systemic manifestations of atherosclerosis have prompted
      a reevaluation of carotid revascularization as the standard of care for patients
      with severe carotid bifurcation stenosis. Endarterectomy and stenting each have
      unique procedure-specific factors that determine whether a patient is at
      increased risk for perioperative complications. Determining which patients are at
      high-risk for these modalities will impact the individualized treatment
      algorithm. This article examines the anatomical and physiologic conditions that
      can affect the anticipated outcome of each treatment modality. Ultimately, a
      tailored approach to each patient's clinical situation is likely to result in the
      best outcome following treatment.

PMID- 18082837
TI  - What are current preprocedure imaging requirements for carotid artery stenting
      and carotid endarterectomy: have magnetic resonance angiography and computed
      tomographic angiography made a difference?
AB  - Determination of degree of carotid artery stenosis is of critical importance when
      deciding whether a patient warrants surgical intervention. While angiography is
      still considered by some to be the true reference standard for imaging the
      internal carotid artery (ICA), physicians rely most commonly on duplex imaging
      when planning for endarterectomy. It is noninvasive, safe, and overall reliable
      for grading stenosis but is nevertheless user-dependent and can be limited in
      cases of severe calcification. Moreover, a lack of consensus for duplex criteria
      can be confounding. In recent years, magnetic resonance angiography (MRA) and
      computed tomographic angiography (CTA) have assumed a more prominent role in the
      preoperative planning for treatment of carotid stenosis. Improved resolution and
      faster acquisition times for both of these imaging modalities have allowed for
      accurate depictions of degree of stenosis, as well as plaque characterization.
      CTA and MRA may have special relevance in the era of carotid stenting, since
      challenging arch anatomy and identification of a high-risk vulnerable plaque may
      be useful when deciding whether to perform a stent procedure or endarterectomy.

PMID- 18082838
TI  - Difficult anatomy: what characteristics are critical to good outcomes of either
      CEA or CAS?
AB  - Whether performing carotid endarterectomy or carotid stenting, patients are
      selected on the basis of their anatomical suitability for these procedures. The
      procedure is then tailored to the specific anatomy with which the patient
      presented. As a result, outcomes of both carotid endarterectomy and stenting are
      significantly influenced by anatomical considerations and good outcomes are
      determined, at least in part, by selecting, understanding, and managing a wide
      variety of anatomical presentations.

PMID- 18082839
TI  - Primary closure, routine patching, and eversion endarterectomy: what is the
      current state of the literature supporting use of these techniques?
AB  - Our objective in this article was to review the most recent literature on the
      status of carotid patching or primary carotid closure following carotid
      endarterectomy; to determine the best patch material if needed; and to clarify
      the place of eversion carotid endarterectomy in management of carotid artery
      atherosclerosis. In order to accomplish this, a literature review was performed
      of the Ovid, PubMed and MedLine databases using appropriate search terms. An
      evidence-based approach was taken; with all articles graded using the Scottish
      Intercollegiate Guidelines Network system (levels of evidence 1 to 5) and
      recommendations were made using an A to D system. Most weight was given to well
      conducted, adequately powered, randomized control trials. After review of the
      literature, we were able to make the following Grade A recommendation: carotid
      patching is superior to primary closure, resulting in fewer postoperative strokes
      and a lower incidence of restenosis in most surgeons' hands. However, it was also
      concluded that, based on review of the literature, that the choice of patch
      material in 2007 has little impact; eversion carotid endarterectomy (CEA) and
      conventional patch CEA have equivalent postoperative morbidity and similar
      incidences of long-term restenosis. In conclusion, the technique of CEA continues
      to evolve, but in most reported series, immediate and long-term outcomes are
      excellent. A variety of technical approaches are acceptable, but it appears that
      carotid patching remains superior to primary closure.

PMID- 18082840
TI  - Intraoperative imaging: does it really improve perioperative outcomes of carotid
      endarterectomy?
AB  - A variety of intraoperative imaging and assessment techniques can be used during
      carotid endarterectomy (CEA) to evaluate the technical results of the arterial
      repair. However, the necessity of utilizing these techniques routinely in every
      case, and the actual ability of these studies to improve the outcomes of the
      operation, remain areas of controversy. The most commonly used intraoperative
      assessment techniques include arteriography, duplex ultrasonography, and use of a
      hand-held continuous-wave Doppler probe. While surgeons who advocate
      intraoperative imaging presume that it will ultimately improve the technical
      "perfection" of the operation by allowing the intraoperative identification and
      immediate revision of occult technical defects that would likely predispose
      toward perioperative stroke, there is little comparative data in the literature
      to support this premise. Proponents of routine intraoperative assessment argue
      that the identification of technical imperfections will allow their immediate
      correction prior to a perioperative stroke resulting from thromboembolization. In
      addition, surgeons who use these techniques believe that the presumed reduction
      in rate of serious technical errors will also result in a lower rate of recurrent
      carotid stenosis. However, many experienced vascular surgeons who perform CEA do
      not routinely utilize any of these intraoperative assessment techniques, and
      report equally excellent results using meticulous technique alone and clinical
      inspection of the endarterectomy site and arterial repair. Potential issues that
      may arise when performing routine intraoperative assessment can include: making a
      determination of which type of "imperfections" actually require immediate
      revision of the arterial repair, and potential vascular injuries or cerebral
      ischemia associated with reclamping of the artery in order to perform an
      immediate revision. In an analysis of a large, population-based cohort study of
      CEAs, the authors have found no compelling evidence that routine use of these
      imaging techniques confers any advantage in terms of the perioperative outcomes
      of carotid endarterectomy. CONCLUSIONS: the majority of surgeons who perform
      carotid endarterectomy do not routinely utilize any formal intraoperative
      completion imaging or assessment technique during CEA, other than clinical
      inspection of the arterial repair. However, even among vascular surgeons, less
      than 50% are routinely using intraoperative imaging or assessment. The routine
      use of intraoperative imaging studies did not appear to significantly improve
      perioperative outcomes with regard to ipsilateral perioperative stroke, and
      stroke/death. Considering the increased time and cost of performing these
      procedures, routine use of intraoperative imaging and assessment techniques
      during CEA is of questionable value. Selective use of these imaging or assessment
      techniques when the surgeon has a specific concern regarding the technical
      outcomes of the operation appears to be a reasonable alternative.

PMID- 18082841
TI  - Embolic protection devices for carotid artery stenting: have they made a
      significant difference in outcomes?
AB  - Carotid angioplasty and stenting (CAS) is a valid alternative to conventional
      carotid endarterectomy for treatment of carotid artery stenosis in a select group
      of patients. Distal embolization of atherosclerotic debris and air causing
      neurologic deficits during CAS has been one of the most significant concerns
      limiting widespread application of CAS technology. A variety of distal embolic
      protection devices have been designed to minimize the risk of major embolization
      causing stroke. This review will examine the types of available devices,
      including strengths and weaknesses of each, and present the available evidence
      and rationale for their routine use during CAS.

PMID- 18082842
TI  - The effect of statin medications on perioperative and long-term outcomes
      following carotid endarterectomy or stenting.
AB  - Statins belong to a class of drugs known to inhibit 3-hydroxy 3-methylglutaryl
      coenzyme A reductase, and block hepatic cholesterol synthesis. Since the initial
      statin was approved by the Food and Drug Administration in 1987, these agents
      quickly became the gold standard for treatment of hypercholesterolemia. Effective
      lipid-lowering has been found to improve the long-term prognosis of patients with
      coronary artery disease. In addition, statins have also been found to be highly
      effective in primary and secondary stroke prevention among medically managed
      patients with cardiovascular disease, and it appears that this benefit is largely
      due to the non-cholesterol-lowering, so-called pleiotropic, effects of statins.
      During the past decade, agents such as beta-blockers, aspirin, or other
      antiplatelet medications have proven to reduce the incidence of adverse
      postoperative outcomes among vascular surgical patients, and have rightfully
      assumed a place in our overall therapeutic armamentarium. There is growing
      evidence that statins may be especially effective in reducing cardiovascular
      morbidity and improving outcomes after major vascular surgery. A recent study
      from Johns Hopkins Hospital demonstrated a threefold reduction in the rate of
      perioperative stroke (P < .05) and fivefold reduction of perioperative mortality
      (P < .05) among 1,566 patients undergoing carotid endarterectomy (CEA). This
      benefit was confirmed in a series of 3,360 CEAs performed at multiple hospitals
      throughout Western Canada. Statin use was independently associated with a 75%
      reduction (odds ratio [OR] = 0.25; 95% confidence interval [CI], 0.07-0.90) in
      the odds of death and 45% reduction (OR = 0.55; 95% CI, 0.32-0.95) in the odds of
      ischemic stroke or death among patients with symptomatic carotid disease.
      Further, there is some data indicating that statin use may reduce long-term
      incidence of restenosis following CEA. Preliminary work indicates that a similar
      benefit of statin use in reducing neurologic morbidity among patients undergoing
      carotid angioplasty and stent procedures. A number of the pleiotropic effects of
      statin medications may be responsible for these clinical observations. Further
      work is necessary to better elucidate these mechanisms, as well as to determine
      the optimal agents, dosing, and timing of drug administration among patients
      undergoing carotid interventions.

PMID- 18082843
TI  - Recurrent carotid stenosis after CEA and CAS: diagnosis and management.
AB  - Carotid endarterectomy (CEA) is the preferred method for cerebral
      revascularization in patients with symptomatic and asymptomatic high-grade
      extracranial carotid artery stenosis. Carotid artery stenting (CAS) has recently
      emerged as a less invasive alternative to endarterectomy. Carotid stenting has
      been demonstrated to be technically feasible and safe in high-risk patients. It
      has been approved as an acceptable method for revascularization in circumstances
      where CEA yields suboptimal results. While the final role of CAS in carotid
      revascularization will be determined on the basis of ongoing randomized trials,
      it is clear that stenting will continue to be performed in subgroups of patients
      with carotid stenosis. Therefore, it is anticipated that there will be a
      corresponding increase in the number of in-stent restenosis cases. Considerable
      controversy exists regarding the clinical significance, natural history,
      threshold for management, and appropriate intervention of recurrent carotid
      stenosis after endarterectomy and after stenting. This review analyzes current
      information on this important clinical problem and presents evidence-based
      recommendations for the diagnosis and management of recurrent carotid stenosis.

PMID- 18082844
TI  - Possible ecological consequences from the Sethu Samudram Canal Project, India.
AB  - The Sethu Samudram Canal Project (SSCP), considered as a harbinger of economic
      growth in India, is a mega engineering project being developed to provide a 260
      km long, 300 m wide and 12 m deep shipping channel between the Arabian Sea and
      the Bay of Bengal. This project impacts the unique biota and biodiversity of a
      10,500 km(2) Marine Biosphere Reserve. This man-made link facilitates exchange of
      water masses between the less saline Bay of Bengal and the more saline Arabian
      Sea. Initial construction, subsequent dredging for channel maintenance, and the
      associated ship traffic would result in irreversible changes to the already over
      exploited and stressed environment. Additionally, the channel would form a deep
      ocean route for future tsunamis. However, to provide assurance to the public,
      particularly the 50,000 fishing folk, in 47 villages in this area, it would be
      crucial that a long-term environmental monitoring program is instituted. A
      thorough evaluation of the impending environmental impacts, similar to those
      addressed by a Before/After and Control/Impact (BACI model) is recommended.

PMID- 18082845
TI  - An intercalibration of classification metrics of benthic macroinvertebrates in
      coastal and transitional ecosystems of the Eastern Mediterranean ecoregion
      (Greece).
AB  - Three coastal and three lagoonal sites located in Greece (Eastern Mediterranean)
      were selected to test and intercalibrate classification methods developed for
      benthic invertebrates ecological quality assessments. These methods were
      developed for the purposes of the European Water Framework Directive which is a
      European legislation adopted for the protection and improvement of the coastal
      and transitional waters. However, through testing these methods, this work
      addresses in general the issue of determining and comparing the ecological status
      of the coastal and transitional macrobenthic communities in Eastern Mediterranean
      ecosystems. Among methods tested were the biotic indices AMBI and BENTIX, the
      multivariate method M-AMBI and the biomass size structure index ISD in lagoonal
      sites only. ISD index is a rather new method developed especially for
      transitional ecosystems and in this contribution its performance is
      intercalibrated with the other benthic classification metrics. Comparison and
      intercalibration of the indices results in assessing the ecological quality
      status (EQS) are presented graphically and statistically performing the Kappa
      analysis. Results of the comparison and the indices' performance are evaluated
      based on the knowledge of the sites' environmental condition and baseline
      studies. Based on an extended dataset of coastal and transitional ecosystems
      benthic invertebrates, an evaluation of each index performance and effectiveness
      is attempted through an insight and comparative analysis of each methods'
      structure and design. Results showed that in these Eastern Mediterranean coastal
      sites the BENTIX index seems to give a more biologically relevant classification
      and gives a higher confidence level regarding the classification compared to the
      other indices. In the coastal areas AMBI showed a tendency for the "good" class
      classification, while the factorial M-AMBI gave more consistent results with the
      BENTIX. In the lagoonal sites the biotic indices tested were not proved efficient
      enough and the biomass based ISD index proved more appropriate for these
      ecosystems. AMBI showed the highest agreement with the ISD which is due to the
      better performance of this index in the slightly and moderately polluted lagoons,
      compared to the other indices. However, AMBI failed to classify the polluted
      lagoon, in which case the BENTIX gave a more relevant classification.

PMID- 18082846
TI  - Methods applied in studies of benthic marine debris.
AB  - The ocean floor is one of the main accumulation sites of marine debris. The study
      of this kind of debris still lags behind that of shorelines. It is necessary to
      identify the methods used to evaluate this debris and how the results are
      presented and interpreted. From the available literature on benthic marine debris
      (26 studies), six sampling methods were registered: bottom trawl net, sonar,
      submersible, snorkeling, scuba diving and manta tow. The most frequent method
      used was bottom trawl net, followed by the three methods of diving. The majority
      of the debris was classified according to their former use and the results
      usually expressed as items per unity of area. To facilitate comparisons of the
      contamination levels among sites and regions some standardization requirements
      are suggested.

PMID- 18082847
TI  - Micronuclei frequency induced by bleomycin in human peripheral lymphocytes:
      correlating BLHX polymorphism with mutagen sensitivity.
AB  - Mutagen sensitivity assay, by measuring chromosome damage induced by an in vitro
      treatment of peripheral lymphocytes with bleomycin, has been proposed as a
      biomarker for assessing cancer susceptibility. Recently, a single nucleotide
      polymorphism (SNP A1450G) of the gene for bleomycin hydrolase (BLHX), a specific
      neutral cysteine protease able to metabolise bleomycin, was proposed as a
      plausible candidate to variation in mutagen sensitivity. To shed more light on
      the effect of BLHX genotype on the expression of chromosome damage induced in
      vitro by bleomycin, we determined mutagen sensitivity for 45 non-smoker healthy
      volunteers. The level of bleomycin-induced chromosome damage was assessed as
      frequencies of micronuclei (MN) in cytokinesis-blocked lymphocytes. The subjects
      were genotyped for the BLHX gene, to determine the possible effect of this
      polymorphism on mutagen sensitivity. No difference in the spontaneous value of MN
      was detected between the homozygotes wild-type (A/A) and the carriers of variant
      alleles A/G heterozygotes or G/G homozygotes (MN/1000 binucleated (BN) cells:
      6.69+/-2.53 and 6.37+/-4.87, respectively). A substantial effect of BLHX
      polymorphism in predetermining individual mutagen sensitivity status was
      observed: subjects with the BLHX A/A genotype displayed significantly lower mean
      levels of bleomycin-induced MN frequency than the carriers of A/G or G/G variant
      alleles combined (12.00+/-3.76 MN/1000 BN vs. 16.37+/-8.86 MN/1000 BN,
      respectively; P=0.029). The multiple regression analysis, including BLHX genotype
      and age, confirmed the significant effect of BLHX variant alleles (A/G, G/G) on
      the chromosome damage induced by bleomycin (P=0.01), whereas age correlated only
      with the spontaneous MN frequency.

PMID- 18082848
TI  - The endogenous OFQ/N/ORL-1 receptor system regulates the rewarding effects of
      acute cocaine.
AB  - Previous studies have shown that orphanin FQ/nociceptin (OFQ/N), the endogenous
      ligand of the opioid receptor-like (ORL-1) receptor, reduces the rewarding and
      addictive properties of cocaine and other drugs of abuse. In the present study,
      using the conditioned place preference (CPP) paradigm, as an animal model of drug
      reward, we assessed whether the rewarding action of acute cocaine would be
      altered in mice lacking the ORL-1 receptor or in wild type mice treated with J
      113397, an ORL-1 receptor antagonist, relative to their saline-treated controls.
      On day 1, mice were tested for their baseline place preferences, in which each
      mouse was placed in the neutral chamber of a three-chambered CPP apparatus,
      allowed to freely explore all the chambers and the amount of time that a mouse
      spent in each conditioning chamber was recorded for 15 min. On days 2-3, mice
      received once daily alternate-day saline/cocaine (15 or 30 mg/kg) conditioning
      for 30 min. On day 4, mice were tested for their postconditioning preferences, as
      described for day 1. In a subsequent study, the effect of J-113397 (3 mg/kg) on
      the rewarding action of acute cocaine (15 mg/kg) was also examined in wild type
      mice. Our results showed that mice lacking the ORL-1 receptor expressed greater
      CPP than their wild type littermates. Furthermore, the rewarding action of
      cocaine was enhanced in the presence of J-113397 in wild type mice. Together, the
      present results suggest that the endogenous OFQ/N/ORL-1 receptor system is
      involved in the rewarding action of acute cocaine.

PMID- 18082849
TI  - Synergism between fluoxetine and the mGlu2/3 receptor agonist, LY379268, in an in
      vitro model for antidepressant drug-induced neurogenesis.
AB  - We examined the interaction between the selective serotonin reuptake inhibitor,
      fluoxetine, and group-II metabotropic glutamate (mGlu) receptors using progenitor
      cells isolated from cultured cerebellar granule cells, considered as an in vitro
      model of antidepressant-drug induced neurogenesis. These cells expressed mGlu3
      receptors negatively coupled to adenylyl cyclase. A 72-h treatment with either
      fluoxetine or low concentrations of mGlu2/3 receptor agonists (LY379268 or 2R,4R
      APDC) enhanced cell proliferation. The action of fluoxetine was mediated by the
      activation of 5-HT(1A) receptors. We found a strong synergism between fluoxetine
      and LY379268 in enhancing cell proliferation and inhibiting cAMP formation. The
      increased cell proliferation induced by fluoxetine+LY379268 was abrogated by the
      cAMP analogue, 8-Br-cAMP, as well as by drugs that inhibit the mitogen-activated
      protein kinase and phosphatidyilinositol-3-kinase pathways. Interestingly,
      fluoxetine and LY379268 also acted synergistically in promoting neuronal
      differentiation when progenitor cells were incubated in the presence of serum.
      These data support the hypothesis that a combination between classical
      antidepressants and mGlu2/3 receptor agonists may be helpful in the experimental
      treatment of depression.

PMID- 18082850
TI  - Morphine-induced analgesic tolerance, locomotor sensitization and physical
      dependence do not require modification of mu opioid receptor, cdk5 and adenylate
      cyclase activity.
AB  - Acute morphine administration produces analgesia and reward, but prolonged use
      may lead to analgesic tolerance in patients chronically treated for pain and to
      compulsive intake in opioid addicts. Moreover, long-term exposure may induce
      physical dependence, manifested as somatic withdrawal symptoms in the absence of
      the drug. We set up three behavioral paradigms to model these adaptations in
      mice, using distinct regimens of repeated morphine injections to induce either
      analgesic tolerance, locomotor sensitization or physical dependence.
      Interestingly, mice tolerant to analgesia were not sensitized to hyperlocomotion,
      whereas sensitized mice displayed some analgesic tolerance. We then examined
      candidate molecular modifications that could underlie the development of each
      behavioral adaptation. First, analgesic tolerance was not accompanied by mu
      opioid receptor desensitization in the periaqueductal gray. Second, cdk5 and p35
      protein levels were unchanged in caudate-putamen, nucleus accumbens and
      prefrontal cortex of mice displaying locomotor sensitization. Finally, naloxone
      precipitated morphine withdrawal did not enhance basal or forskolin-stimulated
      adenylate cyclase activity in nucleus accumbens, prefrontal cortex, amygdala, bed
      nucleus of stria terminalis or periaqueductal gray. Therefore, the expression of
      behavioral adaptations to chronic morphine treatment was not associated with the
      regulation of micro opioid receptor, cdk5 or adenylate cyclase activity in
      relevant brain areas. Although we cannot exclude that these modifications were
      not detected under our experimental conditions, another hypothesis is that
      alternative molecular mechanisms, yet to be discovered, underlie analgesic
      tolerance, locomotor sensitization and physical dependence induced by chronic
      morphine administration.

PMID- 18082851
TI  - Genital herpes and the teen female.

PMID- 18082852
TI  - Every contact with the patient should be therapeutic.

PMID- 18082853
TI  - The HPV vaccine mandate controversy.
AB  - In this editorial we address the controversies surrounding human papillomavirus
      (HPV) vaccine school-entry mandate legislation, but differentiate between the
      mandate debate and issues specific to the vaccine itself. Our goal is not to take
      a stand in favor of or opposed to mandates, but rather to critically examine the
      issues. We discuss the following arguments against HPV vaccine school-entry
      requirements: 1. The public health benefit of mandated HPV vaccination is not
      sufficient to warrant the intrusion on parental autonomy; 2. A vaccine that
      prevents a non-casually transmitted infection should not be mandated; 3. Opt-out
      provisions are inherently unfair to parents who oppose HPV vaccination; 4.
      Limited health care dollars should not be directed toward cervical cancer
      prevention; and 5. The vaccine is expensive and potential problems with supply
      suggest that mandates should not be implemented until insurance coverage and
      supply issues are resolved. Next, we critically evaluate the following critiques
      of HPV vaccination itself: 1. Giving girls HPV vaccine implies tacit consent to
      engage in sexual activity; 2. Giving girls this vaccine will confer a false sense
      of protection from sexually transmitted infections and will lead to sexual
      disinhibition; 3. Children already have too many vaccinations on the immunization
      schedule; 4. Long-term side effects of HPV vaccine are unknown; 5. The vaccine's
      enduring effectiveness is unknown and booster shots may be required; and 6. It is
      wrong to only target girls with HPV vaccine; boys should be vaccinated as well.

PMID- 18082854
TI  - A psychosexual follow-up study of patients with mixed or partial gonadal
      dysgenesis.
AB  - STUDY OBJECTIVE: To provide late adolescent and young adult psychosexual follow
      up information on a consecutive series of patients with either mixed or partial
      gonadal dysgenesis. SETTING: Children's Memorial Health Institute (Warsaw,
      Poland). PARTICIPANTS: 19 patients (age range, 17-26 years), 9 raised as females
      and 10 raised as males. MEASURES: Clinical interview and psychologic tests were
      used to evaluate gender identity, gender role, and sexual behavior. RESULTS: All
      patients raised as male had a normal male gender identity, displayed masculine
      gender role behavior in childhood, and had a heterosexual sexual orientation.
      Seven of the 10 male patients had experienced heterosexual intercourse. Two out
      of nine women did not identify with the female gender. The majority had masculine
      gender role interests in childhood. The female patients were significantly less
      likely to have experienced sexual activity with a partner than the male patients.
      CONCLUSION: Although gender identity differentiated largely in accordance with
      sex assignment or sex of rearing in our sample, the patients reared as female
      appeared to have poorer sexual adjustment than the males. Cultural factors may
      have impacted on this latter outcome.

PMID- 18082855
TI  - Condom misuse among adjudicated girls: associations with laboratory-confirmed
      chlamydia and gonorrhea.
AB  - OBJECTIVES: To identify the prevalence of condom use errors among detained female
      teens and to test two inter-related hypotheses concerning condom failure.
      METHODS: A cross-sectional survey of 134 female teens recruited within eight
      detention facilities. Measures were collected using audio-computer assisted self
      interviewing. Assessment for the presence of C. trachomatis and N. gonorrhoeae
      was also conducted. RESULTS: Five forms of condom use errors/problems were
      common: not discussing condom use with the partner (34.3%), not having a condom
      when one was desired (48.5%), starting sex before application (21.6%), removing
      condoms before sex concludes (26.9%), and breakage (32.8%). Significant,
      associations were found between condom errors/problems and drug/alcohol use.
      Errors/problems with condom use were significantly higher among teens diagnosed
      with an sexually transmitted disease (STD) (P = 0.039 for an index measure; P =
      0.022 for a single-item measure). CONCLUSIONS: Findings suggest that detained
      female teens may have experienced multiple condom use error and problems thereby
      increasing their vulnerability to STD acquisition.

PMID- 18082856
TI  - Adolescent and young women's experience with the vaginal ring and oral
      contraceptive pills.
AB  - STUDY OBJECTIVE: To compare acceptability of the vaginal contraceptive ring to
      that of oral contraceptive pills. DESIGN: Randomized, cross-over, 6-month study.
      SETTING: Urban family planning clinic for young low-income patients.
      PARTICIPANTS: Sexually active females aged 15-21 years (n = 130). INTERVENTIONS:
      Participants were randomly assigned to use the vaginal ring or oral contraceptive
      pills for an initial study interval of three 28-day cycles, followed by three
      cycles of the alternate method. MAIN OUTCOME MEASURES: Participants completed
      surveys about method use, acceptability, and side effects at baseline, after
      three cycles, and after six cycles. We analyzed study data using ANOVA models for
      cross-over designs. RESULTS: We did not detect higher compliance with the ring as
      compared to oral contraceptive pills (P = 0.176), although overall approval of
      the ring was significantly higher on several items measured, including liked
      using method (P = 0.015), would recommend it to friends (P = 0.012), and not as
      hard to remember to use method correctly (P < or = 0.000). Participants were less
      worried about health risks while using the ring (P = 0.006), but reported that
      the ring was more likely to interfere with sex than the pill (P < or = 0.001) and
      that sex partners liked the pill (P = 0.034). Most women did not report
      bothersome side effects with either method. CONCLUSIONS: Adolescent and young
      women showed favorable acceptability of the vaginal contraceptive ring compared
      to oral contraceptive pills.

PMID- 18082857
TI  - Adrenarche and polycystic ovary syndrome: a tale of two hypotheses.
AB  - Polycystic ovary syndrome (PCOS) is an extremely common endocrine disorder
      affecting young women, with the potential for both reproductive and non
      reproductive adverse outcomes. While oligomenorrhea, hyperandrogenism, and cystic
      ovarian morphology are recognized characteristics of this syndrome, the origin of
      these disturbances is not always apparent. During normal growth and development,
      adrenarche, the prepubertal onset of adrenal androgen secretion, results
      phenotypically in pubarche. Gonadarche, which is the ovarian response to
      gonadotropin releasing hormone-mediated gonadotropin secretion, also occurs,
      leading to reproductive competence, namely the establishment of ovulatory cycles,
      repeatedly. In this mini-review, an overview of adrenarche and gonadarche are
      presented, followed by two hypotheses. The first describes an evolutionary role
      for adrenarche: an advantage in the attainment of reproductive competence. The
      second proposes that the path to PCOS be viewed from a developmental perspective,
      namely, that PCOS is a maladaptation of the processes that lead to reproductive
      competence in women. Its defining characteristics of oligomenorrhea,
      hyperandrogenism, and cystic ovarian morphology are the final common pathway of
      multiple possible derangements. Elucidating and understanding these maladaptive
      processes will be the key to future endeavors at prevention and treatment of this
      common reproductive disorder.

PMID- 18082858
TI  - Primary amenorrhea in non-identical twins: an improbable cause.
AB  - BACKGROUND: Primary amenorrhea is often the first presenting symptom in mullerian
      agenesis. A thorough history and physical examination focusing on pubertal
      development assist in diagnosis and management. Mayer-Rokitansky-Kuster-Hauser
      syndrome (MRKH) is the second most common cause of primary amenorrhea with a
      reported incidence of 1:4000. CASE: Non-identical 18-year-old twins presented
      with primary amenorrhea. They both had well developed secondary sexual
      characteristics, with no menarche. One of the twins complained of lower abdominal
      pain. They were initially assessed within a primary care setting. They were
      referred to a secondary care center for further investigations to reach a
      definite diagnosis and management. Further management was planned within a
      multidisciplinary approach involving gynecologists, psychologists and surgeons
      with a special interest in vaginal reconstructive surgery. CONCLUSION: Primary
      amenorrhea affects approximately 5% of amenorrheic women. Diagnosis and
      management are reached by following a diagnostic algorithm. Reports of MRKH in
      siblings or non-identical twins are rare. We believe this to be the first case of
      MRKH syndrome to be reported in dichorionic twins.

PMID- 18082859
TI  - Ovarian inflammatory myofibroblastic tumor in children.
AB  - Inflammatory myofibroblastic tumors or inflammatory pseudotumors are uncommon
      solid tumors that are highly vascularized, have an intermediate prognosis, and
      are associated with local recurrence, and rare metastasis. Inflammatory
      myofibroblastic tumors (IMT) most often are seen in the lung of young adults, but
      there have been reports of these tumors occurring in children, in various sites.
      The authors report a case of an ovarian IMT arising in a six-year-old girl (third
      case reported in the literature), treated by a right adnexectomy with uneventful
      postoperative course, and discuss recent reports.

PMID- 18082860
TI  - Detecting and treating depression among adolescents presenting for reproductive
      care: realizing opportunities.
AB  - This article reviews typical symptoms of depression presented by adolescents in
      the reproductive care practice setting, provides an overview of the assessment
      process, and offers options for referral and/or treatment of this common, yet
      often unrecognized, mood disorder. Because females have a two-fold higher
      prevalence rate of depressive disorders as compared to males of the same age and
      because reproductive care providers have exceptional access to females during the
      early reproductive years, these physicians have a unique, but often unrealized,
      opportunity to detect and initiate treatment and/or referrals for depression in
      adolescent patients. Indeed, adolescents often discuss symptoms of depression
      with their reproductive care provider with an expectation that they will serve as
      a "first responder" in terms of assisting in the management of the depression.
      Thus, it is important that the provider have an understanding of the disorder,
      its symptoms, and possible treatment modalities. Reproductive care providers are
      uniquely qualified to identify, assess, and treat many types of mood disorders in
      adolescent females.

PMID- 18082861
TI  - Teach the teacher: adolescent confidentiality and minor's consent.

PMID- 18082862
TI  - DEET microencapsulation: a slow-release formulation enhancing the residual
      efficacy of bed nets against malaria vectors.
AB  - Textile materials treated with synthetic repellents have the potential to provide
      protection against insect disease vectors but lack the residual activity
      necessary to achieve a prolonged effect or to be cost-effective. DEET MC is a
      formulation of DEET (N,N diethyl-m-toluamide) in which the repellent is gradually
      released from a capsule that binds the repellent. An experiment carried out on
      DEET-treated mosquito netting showed that the formulation repels, inhibits blood
      feeding and kills mosquitoes for a period of at least 6 months under laboratory
      conditions. Such formulations may have the potential for use on nets against
      pyrethroid-resistant mosquitoes or on clothing or bedding materials distributed
      in disasters, emergencies or refugee camp situations.

PMID- 18082863
TI  - Applying the STARD (Standards for Reporting of Diagnostic Accuracy) checklist to
      the 2007 Transfusion article 'Evaluation of a new enzyme-linked immunosorbent
      assay for detection of Chagas antibody in US blood donors'.
AB  - A group of scientists and journal editors developed the STARD (Standards for
      Reporting of Diagnostic Accuracy) checklist to improve the reporting of
      diagnostic accuracy. This checklist provides a standardised framework to ensure
      all relevant information is considered and no potentially important parameters
      are inadvertently overlooked. Whilst the quality of reporting is crucial to the
      understanding of a test's potential performance characteristics, this checklist
      can and should be used not only to assess the reporting itself, but also to
      question any potential flaws in the assay inadvertently overlooked or not
      challenged by others. This article uses the STARD checklist to look at a recent
      report on a new assay for Chagas disease and examines the strength of this work
      against a standard review tool. Potential issues associated with the reporting of
      the work as well as potential issues with the assay are identified and additional
      questions are posed that might help clarify the issues identified.

PMID- 18082864
TI  - Proliferative effect of androst-4-ene-3,17-dione and its metabolites in the
      androgen-sensitive LNCaP cell line.
AB  - As a therapeutic approach for the treatment of androgen-sensitive diseases, it
      would be tempting to lower the level of the potent androgens testosterone (T) and
      dihydrotestosterone (DHT) by using inhibitors of type 3 and type 5 17beta
      hydroxysteroid dehydrogenases (17beta-HSDs). However, the efficiency of such a
      strategy will be optimal only if androst-4-ene-3,17-dione (Delta4-dione), the
      precursor of T, does not possess per se agonist activity on the androgen receptor
      (AR). To determine if the proliferative effect previously observed on AR(+) cells
      for Delta4-dione originates from its direct (per se) action on AR or from its
      transformation into a metabolite, we started a series of experimentations using
      the human prostate cancer LNCaP cell line, which expresses a highly sensitive AR.
      By real-time RT-PCR analysis, we detected type 1 5alpha-reductase (5alpha-R), a
      small amount of type 5 17beta-HSD, but not type 2 5alpha-R nor type 3 17beta-HSD.
      We then studied the transformation of labeled Delta4-dione in LNCaP cells after 1
      7 days and the most important metabolite detected was 5alpha-androstane-3,17
      dione (A-dione), which is the product of 5alpha-R activity. We measured only low
      levels of androsterone (ADT) and epi-ADT. This result was next confirmed by using
      an inhibitor of 5alpha-R that completely inhibited the transformation of Delta4
      dione into A-dione, and consequently into ADT and epi-ADT. The proliferative
      effect of Delta4-dione (carefully purified) on LNCaP (AR(+)) cells was next
      determined in presence or absence of the 5alpha-R inhibitor. Although the cells
      proliferate in the presence of Delta4-dione only, no cell proliferation was
      observed with a combination of Delta4-dione and 5alpha-R inhibitor, suggesting
      that Delta4-dione is not androgenic per se. We next determined that A-dione and
      epi-ADT stimulated cell growth with the same pattern and potency as Delta4-dione,
      whereas ADT had a 3.5-fold lower proliferative activity. In conclusion, Delta4
      dione is not in itself an agonist steroid on LNCaP (AR(+)) cells, and its
      proliferative activity appears to be mediated by its transformation into A-dione
      and/or into epi-ADT.

PMID- 18082866
TI  - Application of fluorescence in situ hybridization technique to detect simazine
      degrading bacteria in soil samples.
AB  - We propose a new approach to evaluate the natural attenuation capacity of soil by
      using fluorescence in situ hybridization (FISH). A specific oligonucleotide probe
      AtzB1 was designed based on the sequence data of the atzB gene involved in the
      hydrolytic deamination of s-triazines; this gene, located in a multiple copy
      plasmid was detected by the optimized FISH protocol. Two agricultural soils (Lodi
      and Henares) with a history of simazine treatments, and two natural soils (Soto
      and Monza), without previous exposure to simazine, were studied. AtzB1 probe
      target cells were found only in the agricultural soils and, in a greater
      percentage, in the Lodi soil, compared to the Henares one. Moreover, the greatest
      percentage of AtzB1 probe-target cells in Lodi was accompanied by a greater
      mineralization rate, compared to the Henares soil. The FISH method used in this
      study was suitable for the detection of simazine-degrading bacteria and could be
      a useful indicator of the potential of soil bioremediation.

PMID- 18082865
TI  - HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF
      3 for degradation.
AB  - The activation of IRF-3 during the early stages of viral infection is critical
      for the initiation of the antiviral response; however the activation of IRF-3 in
      HIV-1 infected cells has not yet been characterized. We demonstrate that the
      early steps of HIV-1 infection do not lead to the activation and nuclear
      translocation of IRF-3; instead, the relative levels of IRF-3 protein are
      decreased due to the ubiquitin-associated proteosome degradation. Addressing the
      molecular mechanism of this effect we show that the degradation is independent of
      HIV-1 replication and that virion-associated accessory proteins Vif and Vpr can
      independently degrade IRF-3. The null mutation of these two genes reduced the
      capacity of the HIV-1 virus to down modulate IRF-3 levels. The degradation was
      associated with Vif- and Vpr-mediated ubiquitination of IRF-3 and was independent
      of the activation of IRF-3. N-terminal lysine residues were shown to play a
      critical role in the Vif- and Vpr-mediated degradation of IRF-3. These data
      implicate Vif and Vpr in the disruption of the initial antiviral response and
      point to the need of HIV-1 to circumvent the antiviral response during the very
      early phase of replication.

PMID- 18082867
TI  - Nitrate reductase, arginine deaminase, urease and dehydrogenase activities in
      natural soil (ridges with forest) and in cotton soil after acetamiprid
      treatments.
AB  - Soil enzymes are indicators of microbial activities in soil and are often
      considered as an indicator of soil health and fertility. They are very sensitive
      to the agricultural practices, pH of the soil, nutrients, inhibitors and weather
      conditions. To understand the effect of an insecticide, acetamiprid (IUPAC Name:
      (E)-N1-[(6-chloro-3-pyridyl) methyl]-N2-cyano-N1-methyl acetamidine) on different
      soil enzyme activities, the experiments were conducted for three consecutive
      years (2003--2005) at control and cotton experimental fields of Indian
      Agricultural Research Institute (IARI) and natural area (ridges with forest) in
      Delhi. The combined results for all three years were presented here to understand
      the impact of acetamiprid on soil enzyme activities. Acetamiprid was applied
      three times in one crop season after 41, 48 and 73 days of sowing, to control the
      pest. Soil of treated fields was analyzed for insecticide residues immediately
      after first insecticide treatment and thereafter at definite period. The residues
      of acetamiprid in experimental soil was varied from 0.30+/-0.13 to 22.67+/-0.2
      microg g(-1)d.wt. soil, during the crop period of 2003. The insecticide residues
      for 2004 ranged between 0.59+/-0.38 and 13.42+/-0.71 microg g(-1)d.wt. soil and
      for 2005 it ranged between 0.48+/-0.22 and 19.81+/-0.33 microg g(-1)d.wt. soil.
      An average half life of acetamiprid in our treated field was 11.2+/-1.7 days for
      all three years. Similarly, the soil from natural area and control were also
      tested for insecticide residues. No detectable insecticide residues had been
      found. Soil from three localities i.e. natural, control and experimental fields
      were tested for different enzyme activities. Nitrate reductase, arginine
      deaminase, urease and dehydrogenase activities were high in natural soil in
      comparison to control soil and insecticide treated soil in all three experimental
      years. At the same time, nitrate reductase activity was all time low in
      acetamiprid treated soil. Acetamiprid had inhibitory effects on nitrate
      reductase, arginine deaminase and urease activities. After first treatment (43
      days after crop sowing), nitrate reductase (41%), arginine deaminase (22%) and
      urease (35%) activities were declined. Dehydrogenase activity increased to 22%
      after first insecticide application. Enzyme activities were recovered at the end
      of each crop season. Therefore, it can be attributed that agricultural practices,
      weather conditions and use of acetamiprid might be responsible for the different
      level of enzyme activities in soil.

PMID- 18082868
TI  - Application of Klebsiella oxytoca immobilized cells on the treatment of cyanide
      wastewater.
AB  - Klebsiella oxytoca, isolated from cyanide-containing industrial wastewater, has
      been shown to be able to biodegrade cyanide to non-toxic end products. The
      technology of immobilized cells can be applied in biological treatment to enhance
      the efficiency and effectiveness of biodegradation. In this study, potassium
      cyanide was used as the target compound and both alginate and cellulose
      triacetate techniques were applied for the preparation of immobilized cells.
      Results from this study show that KCN can be utilized as the sole nitrogen source
      by K. oxytoca. The free suspension systems reveal that the cell viability was
      highly affected by initial KCN concentration and pH. Results show that
      immobilized cell systems could tolerate a higher level of KCN concentration and
      wider ranges of pH. In the batch experiments, the maximum KCN removal
      efficiencies using alginate and cellulose triacetate immobilized beads were 0.108
      and 0.101mM h(-1) at pH 7, respectively. Results also indicate that immobilized
      system can support a higher biomass concentration. Complete KCN degradation was
      observed after the operation of four consecutive degradation experiments with the
      same batch of immobilized cells. This suggests that the activity of immobilized
      cells can be maintained and KCN can be used as the nitrogen source throughout KCN
      degradation experiments. The maximum KCN removal rates using alginate and
      cellulose triacetate immobilized beads in continuous-column system were 0.224 and
      0.192mMh(-1) with initial KCN concentration of 3mM, respectively. Results
      indicate that the immobilized cells of K. oxytoca would be applicable to the
      treatment of cyanide-containing wastewaters.

PMID- 18082869
TI  - Promotion of pyrene degradation in rhizosphere of alfalfa (Medicago sativa L.).
AB  - Pot experiment was conducted to evaluate the phytoremediation of pyrene
      contaminated soil using alfalfa (Medicago sativa L.). Alfalfa biomasses,
      microbial viable counts, dehydrogenase activity, residual pyrene concentration
      and pyrene removal percentage were determined after 60 days of alfalfa growth.
      The results indicated that pyrene had an inhibitive effect on alfalfa growth, and
      higher pyrene concentration seriously affected alfalfa growth. In addition, the
      inhibitive effect on the root was more severe than that on the shoot. When pyrene
      concentration reached 492 mg kg(-1) in soil, the shoot and root biomasses were
      only 34% and 22% of those of alfalfa growing in non-spiked soil, respectively.
      The rhizospheric bacterial and fungi counts were 5.0-7.5 and 1.8-2.3 times higher
      than those in non-rhizosphere soil, respectively. The residual concentrations of
      pyrene in the rhizosphere soil were lower than those in the non-rhizosphere soil.
      After 60 days, 69-85% and 59-80% of spiked pyrene disappeared from the
      rhizosphere and non-rhizosphere soils, respectively. The removal percentage
      decreased with increasing pyrene concentration. However, the average removal of
      pyrene in the rhizosphere soil was 6% higher than that in the non-rhizosphere
      soil. Therefore, the presence of alfalfa roots was effective in promoting the
      phytoremediation of freshly added pyrene into the soil.

PMID- 18082871
TI  - Transendoscopic ultrasound in ventricular lesions.
AB  - BACKGROUND: After transendoscopic sonocatheters had been tested in the laboratory
      for imaging characteristics and practicability, clinical application was studied
      with special reference to imaging and navigation capabilities, practicability,
      safety, and preliminary indications. METHODS: Intraoperative ENS images prepared
      during surgery on 75 selected patients between 1996 and 2005 were examined. There
      were 35 female and 40 male patients, and their mean age was 42 years (range, 2-69
      years). Within this series, there were 28 cases of ventricular lesions
      (ventricular hematomas, tumors, and colloid cyst included, 35 cases) with
      different diagnosis. In most cases, Aloka sono equipment (Aloka Deutschland,
      Dusseldorf, Germany) was used because equipment supplied by this company had
      yielded superior imaging results in the laboratory. This work with patients
      differed from the laboratory work in that 2 sizes (diameters) of catheters were
      used: 6-F catheters for block-shaft endoscopes and 8-F for hollow-shaft
      endoscopes. RESULTS: Imaging: In clinical use, the sonocatheter has superior
      imaging and navigation abilities to those seen in anatomical laboratory work.
      Real-time and online characteristics represent changes such as shifting,
      pulsation, CSF flow, blood flow, and changes in size and form of structures. When
      confronted with clinical problems, this technique still has some limitations such
      as short penetration depth of 3-cm radius and lack of scanning anterior to the
      endoscope. Navigation: The scan is radial 360 degrees and in an orthogonal plane
      to the axis of the endoscope. At the tip of the endoscope it delivers an image
      that looks geometrically like a "brain radar." Because of its real-time
      characteristic, ENS has a navigation capacity that markedly differs from usual
      neuronavigation, but is intuitively usable. Endoneurosonography was applied in 8
      hydrocephali, 3 colloid cysts, 5 intraventricular hematomas, 1 septostomy, 11
      ETVs, 2 cystostomies, 4 multiple cysts, and 1 tumor biopsy cases. Three
      illustrative cases are presented. CONCLUSION: Endoneurosonography is a tool for
      intraoperative real-time and online high-resolution imaging, and neuronavigation
      of endoscopes with a working channel at least 2 mm in diameter; it also has
      application in a wide variety of ventricular lesions. Endoneurosonography is
      limited by short penetration depth and not scanning ahead to the endoscope
      anteriorly.

PMID- 18082872
TI  - Serotonergic neurotransmission mediates hypothermia induced by the N
      phenylpiperazine antipsychotic prototypes LASSBio-579 and LASSBio-581.
AB  - Previous studies have demonstrated that LASSBio-579 and LASSBio-581, two N
      phenylpiperazine derivatives designed for the treatment of schizophrenia, are
      presynaptic dopamine D(2) receptor agonists that induce a hypothermic effect in
      mice that is not mediated by dopamine receptor activation. The aim of the present
      study was to investigate possible serotonergic mechanisms underlying hypothermia
      induced by LASSBio-579 and LASSBio-581 in CF1 mice. The reduction in core
      temperature was dose-dependent (15-60 mg/kg, i.p.) and occurred by the oral route
      (30 mg/kg). Pretreatment with haloperidol (4 mg/kg, i.p.) resulted in a
      synergistic hypothermic effect. Pretreatment with (+/-)DOI (0.25 mg/kg, i.p.), a
      serotonin 5-HT(2A/C) receptor agonist, reduced the hypothermic effect induced by
      LASSBio-579 and LASSBio-581 at 15 and 30 mg/kg, i.p. In contrast, (+/-)DOI
      enhanced the hypothermia induced by both compounds at 60 mg/kg, i.p. The
      serotonin 5-HT1A antagonist WAY 100635 (0.05 mg/kg, s.c.) abolished the
      hypothermia induced by LASSBio-579 and diminished the hypothermia induced by
      LASSBio-581. Pretreatment with LASSBio579 (30 and 60 mg/kg, i.p.) and LASSBio-581
      (60 mg/kg, i.p.) reduced the number of head-twitches induced by (+/-)DOI (2.5
      mg/kg, i.p.). The ear-scratch response induced by (+/-)DOI was inhibited by both
      LASSBio-579 and LASSBio-581 at 60 mg/kg, i.p. These results indicate that LASSBio
      579 and LASSBio-581 have mechanisms of action through the serotonergic
      neurotransmitter system.

PMID- 18082873
TI  - Relationships between multiple self-reported nonadherence measures and pharmacy
      records.
AB  - BACKGROUND: Nonadherence is a momentous problem that confounds optimal medication
      therapy outcomes. Measuring nonadherence presents a number of methodological
      conundrums. Pharmacists and other health practitioners might benefit from a
      simple tool for measuring adherence that correlates well with other, more
      systematic methods. OBJECTIVES: To determine (1) the concordance between monthly
      oral 7-day self-reported nonadherence estimates and a written 7-day self-reported
      estimate of nonadherence at 3 months, (2) the concordance between oral and
      written self-reported nonadherence measures and pharmacy records, and (3) the
      extent to which oral and written self-reported nonadherence measures predict
      current and future medication nonadherence. METHODS: Recruitment involved 8
      Wisconsin community pharmacies within a large managed care organization (MCO) and
      63 patients with new antidepressant prescriptions. Oral and written self-report
      measures were modified from the Brief Medication Questionnaire. Pharmacy records
      were obtained from the pharmacies and MCO. RESULTS: Oral self-reported
      nonadherence estimates during weeks 4, 8, and 12 were significantly correlated
      with written self-reported nonadherence at week 12 (P< or =.05, week 4; P< or
      =.01, week 8; and P< or =.001, week 12). Oral self-reported nonadherence during
      weeks 8 and 12 was significantly correlated with and predictive of adherence
      measured via pharmacy records from months 1 to 6 (P< or =.05). Oral self-reported
      nonadherence at week 4 was significantly correlated to nonadherence from months 1
      to 6 but only predictive of future nonadherence from months 1 to 3. Written self
      report of nonadherence at week 12 was significantly correlated with and
      predictive of nonadherence from months 1 to 6 (P< or =.001). CONCLUSIONS: Oral
      and written self-report measures have moderate to strong concordance with
      pharmacy records. Both self-report methods are significant predictors of
      medication nonadherence over 6 months. This study highlights the strong
      relationship between simple oral questions about medication use and current and
      future nonadherence. Such brief questions help identify sources of nonadherence
      and trigger appropriate interventions.

PMID- 18082874
TI  - Utilization patterns and medication adherence in patients with type 2 diabetes:
      variations based on type of pharmacy (chain vs independent).
AB  - BACKGROUND: Independent pharmacies have demonstrated a positive effect on patient
      satisfaction, dispensing errors, and patient consultation/counseling. However,
      there is a lack of studies demonstrating whether these benefits translate into
      outcomes such as medication adherence. OBJECTIVE: To estimate the variations in
      utilization patterns and adherence to oral hypoglycemic agents (OHAs) based on
      type of pharmacy (chain/independent). METHODS: A retrospective cohort design was
      used to meet the study objective. Newly diagnosed type 2 diabetes patients during
      a 4-year period were identified from a Medicaid claims database. The provider of
      the index prescription was classified as a chain or independent pharmacy.
      Utilization patterns (switching, augmentation, discontinuation, nonmodification)
      and adherence to OHAs (medication possession ratios) were computed for a 12-month
      follow-up period from the date of the index OHA prescription. A multivariate
      framework was used to estimate the effect of type of pharmacy on utilization
      patterns and adherence after controlling for confounding variables. RESULTS: A
      total of 2696 newly diagnosed type 2 diabetes patients were identified
      (independent pharmacy=987; chain pharmacy=1709). Utilization patterns were
      significantly different between the 2 groups with patients filling their
      prescription at a chain pharmacy 1.3 times more likely to augment therapy as
      compared to patients filling prescriptions at an independent pharmacy (P=.035).
      Independent sample t tests indicated that adherence to OHAs (Mean+/-SD) was
      significantly higher for patients filling their prescriptions at a independent
      pharmacy (0.90+/-0.13) as compared to those filling prescriptions at a chain
      pharmacy (0.88+/-0.13, P=.01). Results of a semi-log Ordinary Least Squares model
      also indicated that controlling for covariates, patients filling prescriptions at
      an independent pharmacy had significantly higher adherence to OHAs as compared to
      those filling prescriptions at a chain pharmacy (P=.02). CONCLUSION: Results of
      the study indicated that patients with type 2 diabetes who received their OHAs
      from an independent pharmacy have slightly higher adherence rates as compared to
      those filling their OHA prescriptions at a chain pharmacy.

PMID- 18082875
TI  - Developing the role of pharmacists as members of community mental health teams:
      perspectives of pharmacists and mental health professionals.
AB  - BACKGROUND: People living with bipolar mood disorder and psychotic illnesses in
      Australia primarily access public-sector mental health care through community
      mental health teams (CMHTs). Adverse drug events are common among clients of
      CMHTs taking psychotropic medications. OBJECTIVE: The study aimed to investigate
      and describe a potential role for pharmacists as members of CMHTs. METHODS: Five
      study pharmacists were employed 1 day per week to work with 5 mental health teams
      over a 24-week period. The pharmacists conducted both client and team specific
      activities designed to optimize the use of medications. The pharmacists recorded
      their professional activities in diaries. Audiotaped focus groups were conducted
      with the pharmacists (n=1) and mental health team staff (n=3) at the conclusion
      of the study. Pharmacists' diaries and the transcripts of focus groups were
      thematically content analyzed. RESULTS: Study pharmacists were perceived as
      valuable sources of unbiased and evidence-based drug information for both mental
      health team staff and their clients and caregivers. Mental health team staff
      particularly appreciated the provision of information about nonpsychotropic
      medications. Pharmacists' participation in clinical team meetings was used as an
      opportunity to present medication review findings and recommendations. Liaising
      between medication prescribers and dispensers working in primary and secondary
      care settings was deemed an important additional role; however, participating
      only 1 day per week was considered to delay rapport building and the
      establishment of collaborative working relationships with mental health team
      staff. CONCLUSIONS: Including pharmacists as members of CMHTs addressed an unmet
      need for pharmaceutical services among clients and staff of CMHTs. Pharmacists'
      contributions were welcomed by mental health team staff. The study raised the
      issue of whether pharmacists should be considered as essential and legitimate
      members of interdisciplinary CMHTs.

PMID- 18082876
TI  - Impact of bilingual product information labels on Spanish-speaking adults'
      ability to comprehend OTC information.
AB  - BACKGROUND: There is a steady growth in the Spanish-speaking population in the
      United States. Language may be a barrier in accessing nonprescription medication
      information for the non-English-speaking population. OBJECTIVE: The objective of
      this study was to compare consumer-reported ease of use, product knowledge, and
      intention to purchase over-the-counter (OTC) medications using bilingual Product
      Information Labels (PILs) and currently available label formats in a sample of
      Spanish-speaking consumers. METHODS: Participants were randomly selected from
      Spanish-speaking consumers shopping for OTC medications in pharmacy or grocery
      stores in Houston, TX. Participants viewed 3 label formats (old, new, and PILs)
      for acetaminophen, ibuprofen, and aspirin in a random order. Questionnaires in
      English and in Spanish were provided to consumers after they viewed each label
      format. Domains measured in the questionnaires included ease of use, product
      knowledge, and purchase intention. All responses were measured on a 7-point
      Likert-type scale. Data were recoded and analyzed using SAS (version 9.0) (SAS
      Institute Inc, Cary, NC) to obtain mean scores for each domain. Participants were
      classified according to language proficiency into "Spanish only" and bilinguals.
      Comparative statistics were computed to compare mean scores between label formats
      in each consumer category. RESULTS: A total of 225 questionnaires were collected.
      The mean (+/-standard deviation) age of participants was 38.91 (+/-11.95) years.
      A majority of respondents were Hispanic (97.75%), female (60.54%), and married
      (62.44%). Mean scores from viewing PILs on ease of use, product knowledge, and
      purchase intention were higher than those from viewing the other label formats.
      In the category of consumers who spoke Spanish only, mean scores of PILs were
      significantly higher as compared to those of old and new label formats (P<.05).
      CONCLUSION: Information provided in Spanish on PILs may be very helpful to the
      Spanish-speaking community when selecting nonprescription medications. Policy
      makers and health care providers should consider PILs as an effective means of
      reducing language barriers and providing OTC medication information to the
      Spanish-speaking population in the United States.

PMID- 18082877
TI  - Clinically important potential drug-drug interactions in outpatient settings.
AB  - BACKGROUND: Although many potential drug-drug interactions (DDIs) are discussed
      in the clinical literature, only limited numbers of these are clinically
      important. Little is known about prescribing of agents involved in these
      clinically important DDIs at the national level. OBJECTIVE: This study examined
      concomitant prescribing of drug combinations that have potential for clinically
      important DDIs in outpatient settings in the United States. METHODS: The 2000
      2002 National Ambulatory Medical Care Survey and the outpatient department
      portion of the 2000-2002 National Hospital Ambulatory Medical Care Survey were
      used to examine 25 clinically important DDIs that are most likely to harm
      patients if not detected. Descriptive statistics were used to characterize
      clinically important DDIs, whereas logistic regression analysis was applied to
      outpatient visits to examine patients at risk for clinically important DDIs.
      RESULTS: An estimated 0.63% (95% confidence interval, 0.51-0.75) of outpatient
      visits involving 2 or more medications resulted in prescription combinations with
      potential for clinically important DDIs for an annual visit estimate of 2.26
      million, or annual visit rate of 8.12 visits per 1000 persons. Fourteen of the 25
      prescription combinations with potential for clinically important DDIs were
      prescribed in outpatient settings, with warfarin accounting for many of the
      visits that yielded the prescribing of interacting medications. A majority (82%)
      of the prescriptions for potentially interacting medications occurred in visits
      involving 5 or more medications. The study found that patients over 44 years of
      age, especially elderly, Medicare beneficiaries, and those prescribed multiple
      medications are at risk for receiving prescription combinations with potential
      for a clinically important DDI. CONCLUSIONS: Although a small percentage of
      outpatient visits resulted in prescription combinations with potential for
      clinically important DDIs, these interactions can have significant implications
      due to medication-related morbidity and mortality. Pharmacists can play a
      critical role in managing the medication therapy of patients at risk for
      clinically important DDIs. Further research is needed to evaluate the economic,
      clinical, and humanistic outcomes of clinically important DDIs, especially among
      those at risk.

PMID- 18082878
TI  - Investigating the relationship between the practice of pharmaceutical care,
      construed external image, organizational identification, and job turnover
      intention of community pharmacists.
AB  - BACKGROUND: Pharmacy employers are being challenged to recruit and retain
      qualified employees. OBJECTIVES: Our study hypothesized that pharmacists who
      practice pharmaceutical care have an attractive construed external image (how
      employees think outsiders view their organization), which strengthens their
      organizational identification (perceptions of oneness with or belongingness to
      the organization) and decreases job turnover intention (thoughts of
      quitting/searching for another job). METHODS: A 7-page questionnaire was mailed
      to the homes of a random sample of 759 licensed pharmacists practicing in the
      United States. Participants had the option of returning the completed survey via
      postal mail or a Web site. The study variables were measured with previously
      validated scales. Structural equation modeling with latent variables evaluated
      the hypothesized relationships. Several demographic variables were included.
      RESULTS: Responses were received from 252 subjects (33%); 121 were community
      pharmacists. As hypothesized, organizational identification and job turnover
      intention were significantly related (B=-0.24) as well as construed external
      image and organizational identification (B=0.41). The practice of pharmaceutical
      care and construed external image were not significantly correlated (B=0.10).
      Although not hypothesized, construed external image was directly related to job
      turnover intention (B=-0.25). The effects of the practice of pharmaceutical care
      on job turnover intention were mediated through organizational identification.
      Position had significant effects. CONCLUSIONS: One additional benefit to the
      practice of pharmaceutical care may be strengthened organizational
      identification. Pharmacists' perception of the image of their employer may
      increase organizational identification and decrease job turnover intention. An
      understanding of the organizational identification of pharmacists would be useful
      in decreasing job turnover intention. Given the current demand for pharmacists,
      this is a worthwhile endeavor. Future research should focus on other predictors
      of construed external image and ways to enhance organizational identification.
      Encouraging the practice of pharmaceutical care may be 1 such way.

PMID- 18082879
TI  - Engaging community pharmacists as partners in tuberculosis control: a case study
      from Mumbai, India.

PMID- 18082880
TI  - Quality and in vitro fertilizing ability of cryopreserved cat spermatozoa
      obtained by urethral catheterization after medetomidine administration.
AB  - Quality and in vitro fertilizing ability of frozen-thawed cat semen collected by
      urethral catheterization (CT) or electroejaculation (EE) after medetomidine
      administration were compared. Sperm collection was performed by an urinary tomcat
      catheter and, 4 days apart, by electroejaculation from each of eight tomcats.
      Results showed that semen collected by CT was characterized by lower volume
      (10.5+/-5.3 microL, P<0.05), higher sperm concentration (1868.4+/-999.8 x
      10(6)/mL, P<0.05) and lower pH (7.0+/-0.4, P<0.05) than that collected by EE
      (67.1+/-25.9 microL, 542.9+/-577.9 x 10(6)/mL, and 7.9+/-0.4, respectively).
      Spermatozoa characteristics after thawing at 0, 3 and 6h did not differ between
      the two methods of collection. Also cleavage rate and embryo production from
      oocytes fertilized with frozen-thawed spermatozoa collected by CT or EE showed no
      significant differences (P>0.05). In conclusion, the results obtained in the
      present study indicate that good quality freezable semen can be collected from
      cats by urethral catheterization after medetomidine administration. This new
      method of semen collection appears very useful in practice and, compared with the
      electroejaculation protocol, permits to obtain semen samples characterized by a
      higher concentration of spermatozoa, lower total volume and lower pH.

PMID- 18082881
TI  - A re-appraisal of the morphophenotype and basal lamina coverage of
      cytotrophoblasts in human term placenta.
AB  - A recent study of human placental villi [Mori et al., The cytotrophoblast layer
      of human chorionic villi becomes thinner but maintains its structural integrity
      during gestation, Biol Reprod 76 (2007) 164-172] concluded that cytotrophoblast
      (CT) cells occupy 80% of the basal lamina (BL) surface at term and that
      syncytiotrophoblast (ST) does not make direct contact with the BL. Based on SPINT
      1 localisation using immunofluorescence on cryosections, these conclusions run
      counter to previous light and electron microscopic data suggesting that term CT
      cells cover no more than about 24% of the BL surface. To resolve these
      discrepancies, we have undertaken a stereological study of term placenta using
      transmission electron microscopy (TEM) and a novel immunofluorescence approach.
      Test line lattices were randomly superimposed on TEM images of villous
      trophoblast from 13 normal term placentae. Intersections with the test lines were
      counted to assess the fractional surface of BL occupied by CT cells. After
      trypsin-mediated removal of syncytium, cells in whole-mounted term and first
      trimester villi were stained with cytokeratin 7 to identify CT and then
      visualised by confocal microscopy. CT formed an almost continuous layer in the
      first trimester. In contrast, term CT cells and their processes were found to
      cover only 44% (SD 14%) of the BL surface with intervening regions occupied by
      ST. TEM and confocal images were consistent with the concept of a network of
      'octopoid' CT cells with fine processes extending from a central cell body. Our
      estimates of CT coverage are lower than the recent immunofluorescence estimate
      but greater than earlier TEM estimates. The former may have been biased by
      overprojection (section thickness) effects whilst the latter may be
      underestimates due to failure to include the fine CT cell processes. We conclude
      that CT cells transform from a cuboidal phenotype early in gestation to flattened
      cells with multiple interconnecting processes. The CT layer thins but maintains a
      functional network within which cells intercommunicate without compromising
      substance transfer via the syncytium.

PMID- 18082882
TI  - The impact of postnatal environment on opioid peptides in young and adult male
      Wistar rats.
AB  - Early environmental influences can change the neuronal development and thereby
      affect behavior in adult life. The aim in the present study was to thoroughly
      examine the impact of early environmental factors on endogenous opioids by using
      a rodent maternal separation (MS) model. The endogenous opioid peptide system is
      not fully developed at birth, and short- and/or long-term alterations may occur
      in these neural networks in animals exposed to manipulation of the postnatal
      environment. Rat pups were subjected to one of five rearing conditions; 15 min
      (MS15) litter (l) or individual (i), 360 min (MS360) l or i daily MS, or housed
      under normal animal facility rearing (AFR) conditions during postnatal days 1-21.
      Measurements of immunoreactive (ir) Met-enkephalin-Arg6Phe7 (MEAP) and dynorphin
      B (DYNB) peptide levels in the pituitary gland and in a number of brain areas,
      were performed at three and 10 weeks of age, respectively. MS-induced changes
      were more pronounced in ir MEAP levels, especially in individually separated rats
      at three weeks of age and in litter-separated rats at 10 weeks of age. The
      enkephalin and dynorphin systems have different developmental patterns, dynorphin
      appearing earlier, which may point at a more sensitive enkephalin system during
      the early postnatal weeks. The results provide evidence that opioid peptides are
      sensitive for early environmental factors and show that the separation conditions
      are critical and also result in changes manifesting at different time points. MS
      induced effects were observed in areas related to stress, drug reward and
      dependence mechanisms. By describing effects on opioid peptides, the study
      addresses the possible role of a deranged endogenous opioid system in the
      previously described behavioral consequences of MS.

PMID- 18082883
TI  - Retinoid X receptor alpha is highly phosphorylated in retinoic acid-resistant HL
      60R cells and the combination of 9-cis retinoic acid plus MEK inhibitor induces
      apoptosis in the cells.
AB  - We examined the effects of 9-cis retinoic acid (RA) on the expression levels of
      retinoid X receptor alpha (RXR alpha) and its phosphorylated form (p-RXR alpha)
      in HL-60 and HL-60R cells. 9-cis RA reduced both RXR alpha and p-RXR alpha in HL
      60 cells, but did neither in HL-60R cells. However, when the HL-60R cells were
      treated with the combination of 9-cis RA plus PD98059, MEK inhibitor, the p-RXR
      alpha and RXR alpha proteins all markedly decreased. Moreover, the combination of
      those agents induced apoptosis in HL-60R cells. Phosphorylation of RXR alpha
      might be associated with RA-resistance in HL-60R cells.

PMID- 18082884
TI  - Transitions and turning points: examining the links between child maltreatment
      and juvenile offending.
AB  - OBJECTIVE: The links between child maltreatment and juvenile offending are well
      established. However, the majority of maltreated children do not offend. The
      research presented in this paper examines the impact that timing and chronicity
      of child maltreatment have on juvenile offending. METHODS: Administrative data
      were obtained on all children who were born in Queensland, Australia in 1983 or
      1984 and had contact with child protective services for at least one child
      protection matter (N=5,849). For these children information was obtained on all
      child protection and juvenile justice contacts until the age of 17. These data
      were analyzed using the Semi-Parametric Group-Based trajectory analyses [Nagin,
      D., & Land, L. (1993). Age, criminal careers, and population heterogeneity:
      Specification and estimation of a nonparametric mixed Poisson model. Criminology,
      31, 327-362]. RESULTS: Six distinctive maltreatment trajectory groups were
      identified, distinguished by the frequency of victimization, the age of onset and
      the duration of the maltreatment. Child maltreatment peaked around the transition
      from preschool to primary school and the transition from primary school to
      secondary school. Furthermore, children whose maltreatment trajectory started or
      extended into adolescence were more likely to offend as juveniles than children
      whose maltreatment occurred prior to, but not during, adolescence. CONCLUSIONS:
      Trajectory analysis provides a useful analytical tool for understanding
      heterogeneous nature of child maltreatment and the impact of maltreatment on
      subsequent juvenile offending.

PMID- 18082885
TI  - Orbital radiation for graves ophthalmopathy: a report by the American Academy of
      Ophthalmology.
AB  - OBJECTIVE: To investigate whether orbital radiation offers effective and safe
      treatment for Graves ophthalmopathy. METHODS: Medical literature databases were
      searched to identify all published reports relating to orbital radiation
      treatment for Graves ophthalmopathy. To be included in the technology assessment,
      reports had to provide original data, to report on a case series or uncontrolled
      trial of at least 100 subjects or a randomized clinical trial of any size, to
      focus on orbital radiation for the treatment of Graves ophthalmopathy, and to
      follow-up patients for at least 3 months. Abstracted data included study
      characteristics, patient characteristics, treatment response, and safety
      information. RESULTS: Fourteen studies were included in the technology
      assessment: 5 observational studies and 9 randomized controlled trials. Three of
      the observational studies report on treatment response, with overall favorable
      outcomes for 40% to 97% of patients. Three of the observational studies provided
      intermediate-term safety data. The risk of definite radiation retinopathy is 1%
      to 2% within 10 years after treatment. Patients treated with orbital radiation
      did not have an increased risk of secondary malignancy or premature death. The 9
      randomized trials were qualitatively heterogeneous. Patients with optic
      neuropathy generally were excluded from participating in the randomized trials.
      Three of the randomized trials were sham controlled. None of these studies showed
      that orbital radiation was more efficacious than sham irradiation for improving
      proptosis, lid fissure, or soft tissue changes such as eyelid swelling. Two of
      the 3 sham-controlled randomized trials demonstrated improved vertical range of
      motion in radiation-treated subjects compared with controls. CONCLUSIONS:
      Systematic review of the effect of orbital radiation on Graves ophthalmopathy is
      limited by the lack of standardization and variable quality of published reports.
      Extraocular motility impairment may improve with radiotherapy, although the
      evidence of a treatment effect is mixed in clinical trials. Future studies are
      needed to determine if a potentially beneficial motility effect results in
      improved patient function and quality of life. Level I evidence indicates that
      proptosis, eyelid retraction, and soft tissue changes do not improve with
      radiation treatment. The efficacy of orbital radiation for compressive optic
      neuropathy resulting from Graves ophthalmopathy has not been investigated in
      clinical trials and merits further study. Radiation retinopathy, although rare,
      is a risk of orbital radiation, even in patients without diabetes who receive
      appropriate radiation dose and delivery.

PMID- 18082887
TI  - Nonuniform pressure generation in the optic chiasm may explain bitemporal
      hemianopsia.
AB  - PURPOSE: To measure the pressure in the temporal and central aspects of the
      chiasm simultaneously during compression of the optic chiasm from below with an
      expanding simulated tumor. DESIGN: Experimental study. METHODS: Craniotomies were
      performed on 5 unfixed cadaveric specimens ranging in age from 49 to 89 years,
      and the optic chiasm was exposed. After a pediatric gauge Foley catheter was
      inserted into the sellar region, the temporal side of the chiasm (temporal aspect
      uncrossed fibers) was impaled with a 30-gauge needle connected to a pressure
      transducer. In like fashion, the central portion of the chiasm (crossed fibers)
      was impaled with another 30-gauge needle connected to a pressure transducer on a
      separate channel. The Foley catheter was inflated for a period of 30 seconds to 1
      minute and the pressure in each channel continuously monitored. Multiple trials
      were performed on each of the 5 specimens. MAIN OUTCOME MEASURE: Pressure change
      between the temporal and nasal aspects of the optic chiasm. RESULTS: In all cases
      in which intrachiasmal pressure could be measured, higher pressures were always
      generated in the central aspect of the chiasm than in the temporal aspect of the
      chiasm. In cadaver 1, the mean central pressure was 19.75 mmHg, whereas the mean
      temporal pressure was 6 mmHg. In cadaver 5, the mean central pressure was 4 mmHg,
      whereas the mean temporal pressure was zero. Donors 70 and older demonstrated
      abnormally thin and frail chiasms that were unable to support a sustained
      pressure increase during simulated tumor expansion. CONCLUSIONS: During
      deformation of the optic chiasm from below by a radially expanding mass analogous
      to a pituitary tumor, the central aspect of the optic chiasm consistently
      manifests a higher pressure than the temporal aspect. It is hypothesized that the
      peculiar geometry of the optic chiasm renders the crossing nasal fibers more
      prone to a deformation stress exerted from below. Nonuniform pressure generation
      between the central and temporal aspects of the chiasm results in a greater
      effective stress on the crossing fibers of the chiasm and may be responsible for
      the clinical phenomenon of bitemporal hemianopsia.

PMID- 18082886
TI  - Meta-analysis of 24-hour intraocular pressure studies evaluating the efficacy of
      glaucoma medicines.
AB  - PURPOSE: To evaluate efficacy and safety data of currently available ocular
      hypotensive medicines derived from 24-hour studies, of similar design, in
      patients with primary open-angle glaucoma (POAG), exfoliative glaucoma, or ocular
      hypertension (OH). DESIGN: Meta-analysis of published articles evaluating
      patients with POAG, exfoliative glaucoma, or OH. METHODS: We included articles
      that were randomized, prospective, single- or double-masked, comparative studies
      of ocular hypotensive therapies over 24 hours. Each article selected contained an
      untreated baseline, >or=4-week treatment period, >/=20 patients per treatment
      arm, and >or=6 time points not spaced >5 hours apart and used Goldmann
      applanation or Tonopen tonometry (supine measurements) to measure intraocular
      pressure (IOP). MAIN OUTCOME MEASURE: Twenty-four-hour IOP efficacy. RESULTS:
      This analysis included 864 separate 24-hour treatment curves from 386 patients in
      28 treatment arms from 11 studies. A statistical difference in the mean diurnal
      pressure decrease existed between monotherapy treatments for POAG/OH patients,
      with bimatoprost (29%) and travoprost (27%) showing the greatest 24-hour
      reduction (P = 0.026). Timolol 0.5% was less effective than latanoprost (24% vs.
      19% reduction) but decreased the pressure at each night time point (P = 0.0003).
      Dorzolamide showed a 19% 24-hour pressure reduction and brimonidine 0.2% a 14%
      one. In exfoliative glaucoma patients, latanoprost and travoprost showed higher
      baseline and treatment pressures, although the pressure reductions (29% and 31%,
      respectively) were greater generally than observed with POAG/OH. An evening-dosed
      latanoprost/timolol fixed combination reduced the pressure 33%, and the
      dorzolamide/timolol fixed combination (DTFC), 26%. However, the power to detect a
      difference for this specific comparison was probably low, due to the limited
      number of patients (n = 20) in the DTFC group. A statistical difference between
      evening-dosed (24%) and morning-dosed (18%) latanoprost (P<0.0001) was noted, but
      not between evening (27%) and morning (26%) travoprost (P = 0.074). The mean
      reduction of night time points was statistically lower than day time points for
      latanoprost (P = 0.031), timolol (P = 0.032), and brimonidine (P = 0.050), but
      not for dorzolamide. Dorzolamide (P = 0.60), travoprost (P = 0.064), and
      bimatoprost (P = 0.057) did not demonstrate nighttime pressures lower than
      daytime ones. The mean reduction of night time points was statistically lower
      than that of day time points for latanoprost (P = 0.031), timolol (P = 0.032),
      and brimonidine (P = 0.050), but not for dorzolamide (P = 0.60), bimatoprost (P =
      0.057), travoprost (P = 0.064). CONCLUSIONS: Similar relative efficacies
      generally exist in various classes of ocular hypotensive agents during night and
      day hours.

PMID- 18082888
TI  - Comparison of optic nerve head topography and visual field in eyes with open
      angle and angle-closure glaucoma.
AB  - OBJECTIVE: To compare the optic disc and visual field (VF) alterations in primary
      open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). DESIGN:
      Observational case series. PARTICIPANTS: A total of 146 persons (217 eyes), 110
      with POAG and 36 with PACG, recruited from a university glaucoma service.
      METHODS: Each subject underwent visual acuity measurement, applanation tonometry,
      gonioscopy, slit-lamp examination, dilated optic disc and retinal examination,
      axial eye length measurement, central corneal pachymetry, automated perimetry,
      optical coherence tomography (OCT) nerve fiber layer (NFL) examination, and
      Heidelberg Retina Tomograph (HRT) optic disc evaluation. Parameters of interest
      were studied by multivariate regression models. MAIN OUTCOME MEASURES: Heidelberg
      Retina Tomograph parameters compared between POAG and PACG. RESULTS: Primary open
      angle glaucoma and PACG groups were similar in age, ethnic background, and
      treated intraocular pressure, but the PACG group had significantly more women,
      shorter eye length, more hyperopia, and a larger disc area (all Ps < 0.001). The
      VF average mean deviation (MD) did not significantly differ between POAG and
      PACG, but the PACG group had lower pattern standard deviation (PSD) for a given
      MD (P = 0.001). Although 3 HRT parameters differed somewhat between POAG and PACG
      (cup area, rim area, and cup-to-disc area ratio), they did not significantly
      differ after correction for multiple comparisons. Mean deviation and disc area
      were much more significant predictors of the HRT measures than was diagnosis.
      Similar results were obtained when using OCT NFL thickness as a structural
      measure of damage as opposed to MD as a functional measure. When controlling for
      MD, current IOP was not significantly associated with disc parameters in POAG.
      CONCLUSIONS: When the amount of optic nerve damage is taken into account by
      adjusting for VF MD or OCT NFL thickness, those with POAG and PACG have no
      significant differences in optic disc topography. Visual field damage in PACG was
      more diffuse than that in POAG, as measured by a lower PSD for a given level of
      MD. There was no corresponding difference in the uniformity of structural damage
      as measured by OCT NFL thickness.

PMID- 18082889
TI  - Intraocular pressure fluctuation a risk factor for visual field progression at
      low intraocular pressures in the advanced glaucoma intervention study.
AB  - PURPOSE: To investigate the relationship of intraocular pressure (IOP)
      fluctuation and mean IOP to visual field (VF) progression in patients enrolled in
      the Advanced Glaucoma Intervention Study (AGIS). DESIGN: Retrospective analysis
      of a prospective randomized clinical trial. PARTICIPANTS: Three hundred one eyes
      of 301 patients enrolled in the AGIS were included. Eyes with more than one
      surgical intervention were excluded. METHODS: Worsening of the VF was detected
      with pointwise linear regression. Long-term IOP fluctuation was defined as the
      standard deviation of IOP (millimeters of mercury) at all visits after initial
      intervention until the time of VF worsening or end of follow-up, whichever came
      first. A multivariate linear regression model was performed to identify
      predictors of VF progression. Terciles of mean IOP were identified, and the
      average IOP fluctuation in each stratum was calculated. Terciles of long-term IOP
      fluctuation were similarly evaluated. The proportion of eyes showing VF
      progression in each stratum was determined and compared. MAIN OUTCOME MEASURE:
      Visual field progression. RESULTS: Visual field progression was detected in 78
      eyes (26%). There were statistically significant differences, between progressing
      and nonprogressing eyes, for mean IOP (P = 0.006), IOP fluctuation (P<0.001),
      mean length of follow-up (P = 0.013), mean number of VFs (P = 0.005), and mean
      number of medications (P = 0.006). Three variables were associated with a higher
      probability of VF progression: greater IOP fluctuation (P = 0.009), argon laser
      trabeculoplasty (P = 0.004), and older age (P = 0.05). In this model, mean IOP
      was of borderline statistical significance (P = 0.09). Within the lower and upper
      terciles of mean IOP, IOP fluctuation was associated with VF progression in the
      low mean IOP group (P = 0.002) but not in the high mean IOP group (P = 0.2). When
      subjects were stratified according to IOP fluctuation, there was a statistically
      significant difference between lower and upper terciles of IOP fluctuation with
      respect to progression (P = 0.05). There was a weak correlation between mean IOP
      and IOP fluctuation (r(2) = 0.025, P = 0.01). CONCLUSIONS: In the AGIS, long-term
      IOP fluctuation is associated with VF progression in patients with low mean IOP
      but not in patients with high mean IOP.

PMID- 18082890
TI  - Needling revision of trabeculectomies bleb morphology and long-term survival.
AB  - PURPOSE: To assess the long-term success rate and to determine factors that
      predict survival after 5-fluorouracil-augmented needling revision of poorly
      functioning trabeculectomy blebs. DESIGN: Prospective observational cohort study.
      PARTICIPANTS: Eighty-one consecutive patients undergoing bleb needling. METHODS:
      Survival analysis was performed after a minimum of 2 years' follow-up. Cox
      proportional hazards regression analysis was used to test the association between
      survival and study variables, including bleb morphology. MAIN OUTCOME MEASURES:
      Intraocular pressure (IOP) reduction by >20% and to <or=21 mmHg (definition 1) or
      IOP reduction by >20% and to <or=16 mmHg (definition 2). RESULTS: The mean follow
      up period was 3.4 years. Survival rates were 64.2%, 54.3%, 45.7%, 31.9%, and
      13.0% at 6, 12, 24, 36, and 48 months, respectively, with mean survival of 123.8
      weeks (95% confidence interval [CI], 96.3-151.3; median, 74.0) using definition
      1. Results for definition 2 were not significantly different. Survival time was
      shorter if multiple needlings were employed (P = 0.04) or if an immediate
      reduction in IOP to <or=10 mmHg was not achieved (P<0.001). Preneedling elevated
      bleb morphology was predictive of survival in comparison with flat blebs (P =
      0.02), but this effect was significantly modified by (1) the interval between
      trabeculectomy and needling, (2) degree of bleb vascularization, and (3) presence
      of microcysts. Elevated blebs needled within 3 months of trabeculectomy or blebs
      that were also highly vascularized or microcystic were more likely to survive
      than flat blebs by factors of 4.7, 4.3, and 3.0, respectively (P = 0.002, P =
      0.007, and P = 0.015, respectively). A higher proportion of blebs needled early
      after trabeculectomy survived to 12 months, but the timing of needling did not by
      itself significantly predict survival in the long term. CONCLUSIONS: Needling
      with 5-fluorouracil is an effective intervention in the short to medium term, but
      long-term results show that additional intervention is necessary in the majority
      of cases. Bleb morphology can be used to predict success in recent, highly
      vascularized, or microcystic trabeculectomy blebs.

PMID- 18082891
TI  - Methicillin-resistant Staphylococcus aureus toxic shock syndrome.

PMID- 18082892
TI  - Fear and positive affectivity in infancy: convergence/discrepancy between parent
      report and laboratory-based indicators.
AB  - This study examined convergence between indicators of infant temperament derived
      via parent-report and those obtained in the context of structured laboratory
      observations. Discrepancies between scores resulting from these methodological
      approaches were examined in an attempt to explain these differences by
      considering multiple reporter (i.e., parent) characteristics. Convergence between
      the two sources of information was hypothesized; however, discrepancies were also
      expected. This study was aimed at examining whether increased maternal depression
      and low parenting self-efficacy were related to higher levels of infant fear and
      decreased positive affectivity, as reported by mothers, relative to the scores
      derived from the laboratory procedure. Results indicated that the fear scores
      based on parent-report and structured observations, respectively, were
      significantly correlated; however, the correlation for smiling and laughter
      scores did not reach statistical significance. Furthermore, parents higher in
      negative affect reported a higher level of fear for their infants, relative to
      the results of the laboratory observation.

PMID- 18082893
TI  - Muscarinic acetylcholine receptors as CNS drug targets.
AB  - Muscarinic acetylcholine receptors (mAChRs) are widely expressed in the CNS where
      they control a variety of neuronal functions. Due to their roles in a number of
      CNS processes, mAChRs have long been a target of the drug discovery industry;
      however, the only mAChR ligands approved for use in the clinic are non-selective
      antagonists for the treatment of Parkinson's disease. This article briefly
      reviews recent progress made in mAChR drug discovery for Alzheimer's disease
      (AD), schizophrenia and Parkinson's disease, with particular emphasis on novel
      target validation, as well as highlighting novel indications such as drug
      addiction.

PMID- 18082895
TI  - Screening for bipolar disorder: the utility and comparative properties of the MSS
      and MDQ measures.
AB  - BACKGROUND: Our objective was to further determine the diagnostic utility of the
      Mood Swings Survey (MSS) in distinguishing bipolar and unipolar disorders, and
      draw comparisons between this measure and the widely-used Mood Disorder
      Questionnaire (MDQ). METHODS: A total of 247 consecutively recruited patients
      attending the Black Dog Institute Depression Clinic were administered the Mood
      Swings Survey (MSS) as part of a computerized Mood Assessment Program (MAP), in
      addition to undergoing clinical assessment by two independent psychiatrists. The
      MDQ, along with a structured interview assessing DSM-IV criteria for bipolar
      disorder, was administered to a sub-sample of patients. RESULTS: The MSS-46
      demonstrates comparable sensitivity and specificity to the MDQ (86.5% and 60.0%
      vs. 78.8% and 71.4%) when using pre-established cut-off scores. MSS diagnoses
      embedded within the computerized program correctly classified 82.2% of cases when
      compared to clinician diagnosis. Optimal cut-off scores derived in the current
      sample were > or = 35 (Se=88.5%, Sp=60.0%) for the MSS-46, and > or = 7
      (Se=78.8%, Sp=71.4%) for the MDQ, indicating acceptable stability of cut-off
      scores in differing samples for both measures. LIMITATIONS: ROC analyses
      compromised 'true' estimates of MSS sensitivity and specificity as a number of
      patients who did not affirm the initial screener question were excluded from
      these analyses. CONCLUSIONS: Further work is required to evaluate the diagnostic
      utility of the MSS in differing clinical and community samples to determine the
      stability of its cut-off score and to refine the item set.

PMID- 18082894
TI  - Homeostasis of neuronal avalanches during postnatal cortex development in vitro.
AB  - Cortical networks in vivo and in vitro are spontaneously active in the absence of
      inputs, generating highly variable bursts of neuronal activity separated by up to
      seconds of quiescence. Previous measurements in adult rat cortex revealed an
      intriguing underlying organization of these dynamics, termed neuronal avalanches,
      which is indicative of a critical network state. Here we demonstrate that
      neuronal avalanches persist throughout development in cortical slice cultures
      from newborn rats. More specifically, we find that in spite of large variations
      of average rate in activity, spontaneous bursts occur with power-law distributed
      sizes (exponent -1.5) and a critical branching parameter close to 1. Our findings
      suggest that cortical networks homeostatically regulate a critical state during
      postnatal maturation.

PMID- 18082896
TI  - Psychomotor symptoms in depression: a diagnostic, pathophysiological and
      therapeutic tool.
AB  - BACKGROUND: Psychomotor disturbances have been described repeatedly over many
      centuries. More recently, Sobin and Sackeim [Sobin, C., Sackeim, H.A., 1997.
      Psychomotor symptoms of depression. Am. J. Psychiatry. 154, 4-17.] discussed the
      relevance of psychomotor symptoms in depression in an extensive review. Since
      their report, new pathophysiological, diagnostic and therapeutic findings have
      been published. In the current review of the recent literature, we aim to argue
      the importance of psychomotor symptoms in depression and propose directions for
      future research. METHOD: A review of all the relevant reports on this topic,
      published between 1996 and 2006, was conducted. RESULTS: Several assessment
      methods demonstrate the diagnostic and pathophysiological significance of
      psychomotor symptoms. Antidepressants show differential effects on psychomotor
      performance and findings concerning the symptoms' predictive capacity for
      clinical response are contradictory. Numerous imaging studies as well as studies
      on the neurotransmitter systems and the HPA-axis contribute to the elucidation of
      the neurobiological processes underlying impaired psychomotor functioning in
      depression. CONCLUSIONS: Psychomotor disturbances are of great diagnostic
      significance for the depressive subtype of melancholia. To enhance the
      conceptualisation of the construct 'psychomotor' a standardised battery for their
      assessment is recommended. As to the symptoms' predictive therapeutic power, to
      date research into functional outcome and studies applying objective experimental
      assessment methods are lacking. Moreover, the reported pathophysiological
      importance of dopamine for 'retarded depression' still warrants translation to
      the daily practice.

PMID- 18082897
TI  - Antigen specific immunological responses of badgers (Meles meles) experimentally
      infected with Mycobacterium bovis.
AB  - European badgers (Meles meles) are considered to be an important reservoir of
      infection for Mycobacterium bovis and are implicated in the transmission of
      tuberculosis to cattle in Ireland and Great Britain. Accurate tests are required
      for tuberculosis surveillance in badger populations and to provide a basis for
      the development of strategies, including vaccination, to reduce the incidence of
      the infection. In this study, we have developed an endobronchial M. bovis
      infection model in badgers in which we measured cell-mediated immune and
      serological responses for up to 24 weeks post-infection. Groups of badgers were
      subjected to necropsy at 6-week intervals and the gross lesion severity status
      compared with immune responses measured in blood samples taken throughout the
      course of the study. The panel of antigens included bovine and avian tuberculins
      (PPD) as well as single antigens, ESAT-6, CFP-10, MPB70, Rv3019c, Rv3873, Rv3878
      and Rv3879, all known to be recognised by the immune system in other animal
      models of tuberculosis infection. Our results demonstrated that M. bovis infected
      badgers responded to specific antigens as early as 6 weeks post-infection,
      consistent with the presence of visible lesions. The data also revealed unique
      patterns of antigen recognition with high levels of PBMC proliferation in the
      presence of CFP-10 but low proliferation levels with ESAT-6. Using a multi
      antigen print immunoassay (MAPIA), we were able to confirm that MPB83 is the
      dominant antigen recognised by serum antibodies in infected badgers.

PMID- 18082898
TI  - Lingual thyroglossal duct cyst in newborns: previously misdiagnosed as
      laryngomalacia.
AB  - OBJECTIVE: To distinguish lingual thyroglossal duct cyst (LTDC) from
      laryngomalacia in newborn. METHODS: The clinical data of five newborns who were
      diagnosed as LTDC were retrospectively analyzed. RESULTS: Inspiratory stridor
      with chest wall retraction was cardinal symptom of newborn with LTDC. A slightly
      gray and round cyst with smooth surface at the base of the tongue was found with
      laryngoscopy. In computed tomography examination of larynx, a well-circumscribed
      lesion with low intensity was detected at the base of the tongue protruding into
      the air passage. Pathological examination demonstrated the cyst wall was composed
      of tabular and columnar epithelium. CONCLUSIONS: LTDC is a common disease in
      newborns, which is similar with laryngomalacia. For neonate suspected of LTDC,
      laryngoscopy examination should be taken first, while laryngeal CT scan is an
      important diagnosis basis to be reg. Cyst puncture can ameliorate the symptoms of
      LTDC, while surgical removal serves as a radical cure for LTDC.

PMID- 18082899
TI  - Childhood granular cell tumors: two case reports.
AB  - Granular cell tumors (GCT), also known as Abrikossoff tumors, are rare tumors
      found largely in children, with few reports of laryngo-tracheal involvement. Two
      childhood cases of laryngo-tracheal GCT are reported here, of which one case had
      multifocal lesions. The histopathological features and the therapeutic management
      of GCT are also discussed.

PMID- 18082900
TI  - Lack of association of CT findings and surgical drainage in pediatric neck
      abscesses.
AB  - OBJECTIVE: To evaluate the relationship between neck abscess characteristics on
      computerized tomography (CT) scan and surgical drainage in pediatric patients.
      METHODS: Retrospective data warehouse review identified 43 children younger than
      19 years admitted to a tertiary care pediatric hospital during the first quarters
      of 2000 through 2003 who underwent CT imaging for suspicion of head and neck
      abscesses involving the neck; face; and peritonsillar, retropharyngeal, and
      parapharyngeal spaces. A total of 45 scans were graded by a radiologist blinded
      to management. Thickness of the prevertebral soft tissue; location, dimensions,
      and degree of enhancement of the abscess; patient age; steroid and preadmission
      antibiotic use; and surgical intervention were recorded. RESULTS: Surgical
      drainage was performed in 32 of 43 patients (74%). We found no significant
      correlation between prevertebral soft tissue thickness, abscess dimensions or
      enhancement on CT scan, and surgical drainage. There was no significant
      association between surgical drainage and patient age, administration of
      steroids, or preadmission antibiotic use. CONCLUSIONS: Neck abscess appearance on
      CT scan did not predict surgical drainage, although prevertebral soft tissue
      thickness and abscess dimensions may be important features. Abscess enhancement,
      patient age, and the use of steroids and prehospitalization antibiotics were not
      found to correlate with surgical drainage.

PMID- 18082901
TI  - Quantitative evaluation of viral fitness due to a single nucleotide polymorphism
      in the Marek's disease virus UL41 gene via an in vitro competition assay.
AB  - Marek's disease, a T cell lymphoma, is an economically important disease of
      poultry caused by the Marek's disease virus (MDV), a highly cell-associated
      alphaherpesvirus. A greater understanding of viral gene function and the
      contribution of sequence variation to virulence should facilitate efforts to
      control Marek's disease in chickens. To characterize a naturally occurring single
      nucleotide polymorphism (SNP; AY510475:g.108,206C>T) in the MDV UL41 gene that
      results in a missense mutation (AAS01683:p.Arg377Cys), bacterial artificial
      chromosome (BAC)-derived MDVs that differed only in the UL41 SNP were evaluated
      using a head-to-head competition assay in vitro. Monitoring the frequency of each
      SNP by pyrosequencing during virus passage determined the ratio of each viral
      genome in a single monolayer, which is a very sensitive method to monitor viral
      fitness. MDV with the UL41*Cys allele showed enhanced fitness in vitro. To
      evaluate the mechanism of altered viral fitness caused by this SNP, the virion
      associated host shutoff (vhs) activity of both UL41 alleles was determined. The
      UL41*Cys allele had no vhs activity, which suggests that enhanced fitness in
      vitro for MDV with inactive vhs was due to reduced degradation of viral
      transcripts. The in vitro competition assay should be applicable to other MDV
      genes and mutations.

PMID- 18082902
TI  - Identification of enterovirus serotypes by pyrosequencing using multiple
      sequencing primers.
AB  - Human enteroviruses (HEV) are considered as one of the major causes of central
      nervous system infections in pediatrics. They are currently classified into five
      species involving more than 60 officially recognized serotypes. This study
      describes a rapid molecular method, based on pyrosequencing of a VP1 fragment,
      for the identification of enterovirus serotypes. In order to do so, 200 isolates
      and clinical specimens that were first grouped into 62 different HEV serotypes
      using neutralization test, were analyzed by pyrosequencing. All serotypes were
      identified using the proposed method. Most of the isolates previously untypeable
      by classical procedures, as well as mixed enterovirus infections containing
      viruses belonging to different species, could also be determined using
      pyrosequencing. The present results give support to pyrosequencing as an
      efficient method of HEV genotyping.

PMID- 18082903
TI  - Impacts of short-term acid and aluminum exposure on Atlantic salmon (Salmo salar)
      physiology: a direct comparison of parr and smolts.
AB  - Episodic acidification resulting in increased acidity and inorganic aluminum
      (Al(i)) is known to impact anadromous salmonids and has been identified as a
      possible cause of Atlantic salmon population decline. Sensitive life-stages such
      as smolts may be particularly vulnerable to impacts of short-term (days-week)
      acid/Al exposure, however the extent and mechanism(s) of this remain unknown. To
      determine if Atlantic salmon smolts are more sensitive than parr to short-term
      acid/Al, parr and smolts held in the same experimental tanks were exposed to
      control (pH 6.3-6.6, 11-37 microgl(-1) Al(i)) and acid/Al (pH 5.0-5.4, 43-68
      microgl(-1) Al(i)) conditions in the lab, and impacts on ion regulation, stress
      response and gill Al accumulation were examined after 2 and 6 days. Parr and
      smolts were also held in cages for 2 and 6 days in a reference (Rock River, RR)
      and an acid/Al-impacted tributary (Ball Mountain Brook, BMB) of the West River in
      Southern Vermont. In the lab, losses in plasma Cl(-) levels occurred in both
      control parr and smolts as compared to fish sampled prior to the start of the
      study, however smolts exposed to acid/Al experienced additional losses in plasma
      Cl(-) levels (9-14 mM) after 2 and 6 days, and increases in plasma cortisol (4.3
      fold) and glucose (2.9-fold) levels after 6 days, whereas these parameters were
      not significantly affected by acid/Al in parr. Gill Na(+),K(+)-ATPase (NKA)
      activity was not affected by acid/Al in either life-stage. Both parr and smolts
      held at BMB (but not RR) exhibited declines in plasma Cl(-), and increases in
      plasma cortisol and glucose levels; these differences were significantly greater
      in smolts after 2 days but similar in parr and smolts after 6 days. Gill NKA
      activity was reduced 45-54% in both life-stages held at BMB for 6 days compared
      to reference fish at RR. In both studies, exposure to acid/Al resulted in gill Al
      accumulation in parr and smolts, with parr exhibiting two-fold greater gill Al
      than smolts after 6 days. Our results indicate that smolts are more sensitive
      than parr to short-term acid/Al. Increased sensitivity of smolts appears to be
      independent of a reduction in gill NKA activity and greater gill Al accumulation.
      Instead, increased sensitivity of smolts is likely a result of both the
      acquisition of seawater tolerance while still in freshwater and heightened stress
      responsiveness in preparation for seawater entry and residence.

PMID- 18082905
TI  - Dose calculations accounting for breathing motion in stereotactic lung
      radiotherapy based on 4D-CT and the internal target volume.
AB  - PURPOSE: The purpose of this study was to determine the 4D accumulated dose
      delivered to the CTV in stereotactic radiotherapy of lung tumours, for treatments
      planned on an average CT using an ITV derived from the Maximum Intensity
      Projection (MIP) CT. METHODS: For 10 stage I lung cancer patients, treatment
      plans were generated based on 4D-CT images. From the 4D-CT scan, 10 time-sorted
      breathing phases were derived, along with the average CT and the MIP. The ITV
      with a margin of 0mm was used as a PTV to study a worst case scenario in which
      the differences between 3D planning and 4D dose accumulation will be largest.
      Dose calculations were performed on the average CT. Dose prescription was 60Gy to
      95% of the PTV, and at least 54Gy should be received by 99% of the PTV. Plans
      were generated using the inverse planning module of the Pinnacle(3) treatment
      planning system. The plans consisted of nine coplanar beams with two segments
      each. After optimisation, the treatment plan was transferred to all breathing
      phases and the delivered dose per phase was calculated using an elastic body
      spline model available in our research version of Pinnacle (8.1r). Then, the
      cumulative dose to the CTV over all breathing phases was calculated and compared
      to the dose distribution of the original treatment plan. RESULTS: Although
      location, tumour size and breathing-induced tumour movement varied widely between
      patients, the PTV planning criteria could always be achieved without compromising
      organs at risk criteria. After 4D dose calculations, only very small differences
      between the initial planned PTV coverage and resulting CTV coverage were
      observed. For all patients, the dose delivered to 99% of the CTV exceeded 54Gy.
      For nine out of 10 patients also the criterion was met that the volume of the CTV
      receiving at least the prescribed dose was more than 95%. CONCLUSIONS: When the
      target dose is prescribed to the ITV (PTV=ITV) and dose calculations are
      performed on the average CT, the cumulative CTV dose compares well to the planned
      dose to the ITV. Thus, the concept of treatment plan optimisation and evaluation
      based on the average CT and the ITV is a valid approach in stereotactic lung
      treatment. Even with a zero ITV to PTV margin, no significantly different dose
      coverage of the CTV arises from the breathing motion induced dose variation over
      time.

PMID- 18082904
TI  - The canine hookworm genome: analysis and classification of Ancylostoma caninum
      survey sequences.
AB  - Hookworms infect nearly a billion people. The Ancylostoma caninum hookworm of
      canids is a model for studying human infections and information from its genome
      coupled with functional genomics and proteomics can accelerate progress towards
      hookworm control. As a step towards a full-scale A. caninum genome project, we
      generated 104,000 genome survey sequences (GSSs) and determined the genome size
      of the canine hookworm. GSSs assembled into 57.6 Mb of unique sequence from a
      genome that we estimate by flow cytometry of isolated nuclei to be 347 +/- 1.2
      Mb, substantially larger than other Rhabditina species. Gene finding identified
      5538 genes in the GSS assembly, for a total of 9113 non-redundant A. caninum
      genes when EST sequences are also considered. Functional classifications of many
      of the 70% of genes with homology to genes in other species are provided based on
      gene ontology and KEGG associations and secreted and membrane-bound proteins are
      also identified.

PMID- 18082906
TI  - Estimation of risk of radiation-induced carcinogenesis in adolescents with
      nasopharyngeal cancer treated using sliding window IMRT.
AB  - PURPOSE: To estimate the risk of radiation-induced carcinogenesis based on whole
      body dose measurement on adolescent patients undergoing intensity-modulated
      radiotherapy (IMRT). METHODS AND MATERIALS: Ten adolescent patients with
      nasopharyngeal cancer were planed and treated to a dose of 70.2 Gy using sliding
      window IMRT. Peripheral dose (PD) was measured using thermoluminescent dosimeters
      kept at anterior, lateral and posterior positions of each axial plane at the
      level of xiphoid process, umbilicus and gonads of every patient. The associated
      risk of radiation-induced carcinogenesis was estimated based on the measured
      whole-body dose and using age- and sex-specific ICRP-60 nominal probability
      coefficient of 7.5% (boys) and 9.5% (girls) per Sv. RESULTS: In all patients,
      measured PD per monitor unit (MU) decreases almost exponentially with out-of
      field distance and varies with gantry angle. Highest whole-body dose equivalent
      ranged from 0.5318 to 0.9867 Sv (mean=0.8141 Sv, SD=0.138) which was measured
      posteriorly at the level of xiphoid process. Whole-body dose was represented by
      the average dose at xiphoid process and all measurement positions ranged from
      0.3661 to 0.8766 Sv (mean=0.658 Sv, SD=0.16) and 0.2267 to 0.5277 Sv (mean=0.3859
      Sv, SD=0.09), respectively. The associated mean risk of radiation-induced
      carcinogenesis estimated based on different representation of mean whole-body
      dose was 6.57%, 5.3% and 3.11%, respectively. Higher mean risk of 7.32% was
      estimated among girls as compared to 6.25% for boys. CONCLUSIONS: Knowledge of
      risk of secondary malignancy is particularly important in adolescents and should
      be considered when choosing the optimal treatment technique and delivery system.

PMID- 18082907
TI  - Detection of a novel circovirus in mute swans (Cygnus olor) by using nested broad
      spectrum PCR.
AB  - Circoviruses are the causative agents of acute and chronic diseases in several
      animal species. Clinical symptoms of circovirus infections range from depression
      and diarrhoea to immunosuppression and feather disorders in birds. Eleven
      different members of the genus Circovirus are known so far, which infect pigs and
      birds in a species-specific manner. Here, a nested PCR was developed for the
      detection of a broad range of different circoviruses in clinical samples. Using
      this assay, a novel circovirus was detected in mute swans (Cygnus olor) found
      dead in Germany in 2006. Sequence analysis of the swan circovirus (SwCV) genome,
      amplified by multiply primed rolling-circle amplification and PCR, indicates that
      SwCV is a distinct virus most closely related to the goose circovirus (73.2%
      genome sequence similarity). Sequence variations between SwCV genomes derived
      from two different individuals were high (15.5% divergence) and mainly confined
      to the capsid protein-encoding region. By PCR testing of 32 samples derived from
      swans found dead in two different regions of Germany, detection rates of 20.0 and
      77.3% were determined, thus indicating a high incidence of SwCV infection. The
      clinical significance of SwCV infection, however, needs to be investigated
      further.

PMID- 18082908
TI  - A coupled drug kinetics-cell cycle model to analyse the response of human cells
      to intervention by topotecan.
AB  - A model describing the response of the growth of single human cells in the
      absence and presence of the anti-cancer agent topotecan (TPT) is presented. The
      model includes a novel coupling of both the kinetics of TPT and cell cycle
      responses to the agent. By linking the models in this way, rather than using
      separate (disjoint) approaches, it is possible to illustrate how the drug
      perturbs the cell cycle. The model is compared to experimental in vitro cell
      cycle response data (comprising single cell descriptors for molecular and
      behavioural events), showing good qualitative agreement for a range of TPT dose
      levels.

PMID- 18082909
TI  - A rule-based computer scheme for centromere identification and polarity
      assignment of metaphase chromosomes.
AB  - Automatic centromere identification and polarity assignment are two key factors
      in the automatic karyotyping of human chromosomes. A multi-stage rule-based
      computer scheme has been investigated to automatically detect centomeres and
      determine polarities for both abnormal and normal metaphase chromosomes. The
      scheme first implements a modified thinning algorithm to identify the medial axis
      of a chromosome and extracts three feature profiles. Based on a set of pre
      optimized classification rules, the scheme adaptively identifies the centromere
      and then assigns corresponding polarity. An image dataset of 2287 chromosomes
      acquired from 24 abnormal and 26 normal Giemsa metaphase cells is utilized to
      optimize and test the scheme. The overall accuracy is 91.4% for centromere
      identification and 97.4% for polarity assignment. The experimental results
      demonstrate that our scheme can be successfully applied to diverse chromosomes,
      which include those severely bent and abnormal chromosomes extracted from cancer
      cells.

PMID- 18082910
TI  - Altruism in insect societies and beyond: voluntary or enforced?
AB  - The altruism of insect workers has puzzled researchers for decades. Inclusive
      fitness theory suggests that high relatedness has been key in promoting such
      altruism. Recent theory, however, indicates that the intermediate levels of
      relatedness found within insect societies are too low to directly cause the
      extreme altruism observed in many species. Instead, recent results show that
      workers are frequently coerced into acting altruistically. Hence, the altruism
      seen in many modern-day insect societies is not voluntary but enforced. Here, we
      also consider the role of coercion in promoting altruism and cooperation in other
      social systems, such as vertebrate and human societies, and interspecific
      mutualisms.

PMID- 18082911
TI  - Proenkephalin expression and enkephalin release are widely observed in non
      neuronal tissues.
AB  - Enkephalins are opioid peptides that are found at high levels in the brain and
      endocrine tissues. Studies have shown that enkephalins play an important role in
      behavior, pain, cardiac function, cellular growth, immunity, and ischemic
      tolerance. Our global hypothesis is that enkephalins are released from non
      neuronal tissues in response to brief ischemia or exercise, and that this release
      contributes to cardioprotection. To identify tissues that could serve as
      potential sources of enkephalins, we used real-time PCR, Western blot analysis,
      ELISA, immunofluorescence microscopy, and ex vivo models of enkephalin release.
      We found widespread expression of preproenkephalin (pPENK) mRNA and production of
      the enkephalin precursor protein proenkephalin (PENK) in rat and mouse tissues,
      as well as in tissues and cells from humans and pigs. Immunofluorescence
      microscopy with anti-enkephalin antisera demonstrated immunoreactivity in rat
      tissues, including heart and skeletal muscle myocytes, intestinal and kidney
      epithelium, and intestinal smooth muscle cells. Finally, isolated tissue studies
      showed that heart, skeletal muscle, and intestine released enkephalins ex vivo.
      Together our studies indicate that multiple non-neuronal tissues produce PENK and
      release enkephalins. These data support the hypothesis that non-neuronal tissues
      could play a role in both local and systemic enkephalin-mediated effects.

PMID- 18082913
TI  - QSAR, action mechanism and molecular design of flavone and isoflavone derivatives
      with cytotoxicity against HeLa.
AB  - The quantitative structure-activity relationship (QSAR) of 32 flavone and
      isoflavone derivatives with cytotoxicity expressed as pGC50, which is defined as
      the negative value of the logarithm of necessary molar concentration of this
      series of compounds to cause 50% growth inhibition against the human cervical
      epithelioid carcinoma cell line (HeLa), has been studied by using the density
      functional theory (DFT), molecular mechanics (MM2) and statistical methods. In
      order to obtain QSAR model with high predictive ability, the original dataset was
      randomly divided into a training set comprising 26 compounds and a test set
      comprising the rest 6 compounds. An optimal model for the training set with
      significant statistical quality (RA2=0.852) and predictive ability (q2=0.818) was
      established. The same model was further applied to predict pGC50 values of the 6
      compounds in the test set, and the resulting predictive correlation coefficient
      Rpred2 reaches 0.738, further showing that this QSAR model has high predictive
      ability. It is very interesting to find that the cytotoxicities of these
      compounds against HeLa appear to be mainly governed by two quantum-chemical
      factors, i.e., the energy (ELUMO) of the lowest unoccupied molecular orbital
      (LUMO) and the net charges of C atom at site 6 on aromatic rings (QC6). Here the
      possible action mechanism of these compounds was analyzed and discussed in
      detail, in particular, the fact why the flavone derivatives have considerably
      higher cytotoxicity than isoflavone derivatives was reasonably explained. Based
      on this QSAR equation, 5 new compounds with higher cytotoxicity have been
      theoretically designed. Such results can offer useful theoretical references for
      experimental works.

PMID- 18082912
TI  - Ethanol induces glutamate secretion by Ca2+ mobilization and ROS generation in
      rat hippocampal astrocytes.
AB  - In this study we have investigated the effect of ethanol on [Ca2+]c by
      microfluorimetry and glutamate secretion using an enzyme-linked system, in rat
      hippocampal astrocytes in culture. Our results show that ethanol (1-200 mM)
      evoked a dose-dependent increase in glutamate secretion. 50 mM ethanol, a
      concentration within the range of blood alcohol levels in intoxicated humans,
      induced a release of Ca2+ from intracellular stores in the form of oscillations.
      Ca2+-mobilizing effect of ethanol was not prevented by preincubation of cells in
      the presence of 2 mM of the antioxidant dithiothreitol. Ethanol-evoked glutamate
      secretion was reduced when extracellular Ca2+ was omitted (medium containing 0.5
      mM EGTA) and following preincubation of astrocytes in the presence of the
      intracellular Ca2+ chelator 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic
      acid tetraacetoxy-methyl ester (10 microM). Preincubation of astrocytes in the
      presence of 2 mM of the antioxidant dithiothreitol significantly reduced ethanol
      evoked glutamate secretion. Finally, preincubation of astrocytes in the presence
      of bafilomycin (50 nM) significantly reduced ethanol-induced neurotransmitter
      release, indicating that exocytosis is involved in glutamate secretion. In
      conclusion, our results suggest that ethanol mobilizes Ca2+ from intracellular
      stores, and stimulates a Ca2+-dependent glutamate secretion, probably involving
      reactive oxygen species production, and therefore creating a situation
      potentially leading to neurotoxicity in the hippocampus.

PMID- 18082914
TI  - TBE infection in an incomplete immunized person at-risk who lives in a high
      endemic area--impact on current recommendations for immunization of high-risk
      groups.
AB  - This is a case report on a 50-year-old patient, working as a forest guard in a
      high-endemic region. The subject was immunized with two doses of FSME Immun 0.5
      Baxter vaccine (with a time interval of 18 days between the two doses). Approx.
      two months after the second vaccination the subject developed symptoms of Tick
      borne encephalitis. Clinical course and laboratory findings confirmed diagnosis
      of meningo-encephalo-myelitis with moderate sequelae 1 year after infection.
      Based on this clinical case we recommend in subjects with an accumulation of risk
      factors, as age older than 50 years who are living and working in high-endemic
      areas, a vaccination with conventional schedule (at least two doses applied at 0
      to 1-3 months) ahead of TBE season or a rapid schedule with three doses (0, 7 and
      21 days) of vaccine.

PMID- 18082915
TI  - The perichondrial cutaneous graft and "flip-flop" flap in facial reconstruction:
      a series of 41 cases.
AB  - Reconstruction of defects of the nose and eyelids can be challenging. The
      standard surgical options include full thickness skin grafts and local flaps.
      Another technique that offers a reliable and dimensionally stable one-stage
      reconstruction is the perichondrial cutaneous graft. The donor site is closed
      with the postauricular flip-flop flap. We have used these techniques in a series
      of 41 consecutive patients. Good or excellent aesthetic reconstructions were
      obtained in 39 cases, with 3 complications: 1 failed graft, and 2 small
      postauricular wound dehiscences. The perichondrial cutaneous graft can produce
      excellent cosmetic results when it is used to reconstruct complex defects of the
      nose and eyelid. Closure of the donor site in the conchal bowl with the flip-flop
      flap is a reliable and elegant technique.

PMID- 18082916
TI  - Carotid artery injury during mandibular distraction.
AB  - BACKGROUND: Mandibular distraction is an effective treatment for mandibular
      hypoplasia. Special care must be done while performing the corticotomies to
      prevent injuries to blood vessels or nerves nearby. A rare iatrogenic severe
      injury occurred while performing this operation. REPORT OF PATIENT: A 3 year-old
      girl was operated upon to correct mandibular hypoplasia. A rotating saw was used
      to perform corticotomies in the mandibular angle. In the right side occurred
      acute bleeding and in the saw there was a piece of a blood vessel that was 15 mm
      long and 2 mm in diameter with an open lumen. Exploration of the neck revealed
      that the most distal segment of the internal carotid artery was severed, with a
      thrombus in the proximal end. The distal segment retracted into the temporal bone
      without bleeding. The proximal artery was ligated. After recovery she moved well.
      A computed tomogram was normal and further condition improved clinically.
      CONCLUSION: This complication from the use of a rotary saw has not been
      documented previously and it must be prevented by using some protection behind
      the bone.

PMID- 18082917
TI  - Interposition grafts for difficult carotid artery reconstruction: a 17-year
      experience.
AB  - Carotid interposition grafts (CIP) for carotid artery revascularization can be a
      viable alternative to carotid endarterectomy (CEA) or carotid artery stenting
      (CAS) for complex carotid disease. This is a retrospective review of the UCLA 17
      year experience with CIP for carotid reconstruction. Carotid operations performed
      between 1988 and 2005 revealed 41 CIP procedures in 39 patients using
      polytetrafluoroethylene (PTFE, n = 31) or reversed greater saphenous vein (Vein)
      (n = 10). Perioperative data and long-term follow-up for each conduit were
      statistically compared. There were no significant differences in demographics,
      risk factors, operative indications, complications, or 30-day perioperative
      deaths. There was one postoperative stroke in each group, for an overall stroke
      rate of 4.9% (PTFE 3.2%, Vein 10%). There was one asymptomatic occlusion and
      there were two high-grade restenoses in the PTFE group compared with one
      asymptomatic occlusion and one high-grade restenosis in the Vein group. Overall
      primary patency was 90% and the assisted primary patency was 97% for the PTFE
      group (mean follow-up 50 months), whereas primary patency was 80% (mean follow-up
      30 months) in the Vein group. CIP is a safe and effective technique with
      excellent long-term follow-up for complex carotid reconstruction when CEA or CAS
      may be contraindicated.

PMID- 18082918
TI  - Carotid artery stenting: what have we learned from the clinical trials and
      registries and where do we go from here?
AB  - As with other minimally invasive surgical procedures, carotid angioplasty and
      stenting (CAS) has developed rapidly over the last decade. Although many believe
      equivalency with carotid endarterectomy has been established in high-risk
      patients, the effectiveness of CAS in lower-risk patients is not yet established.
      This report aims to provide a comprehensive and critical review of the trials and
      registries of CAS and to offer insight into future directions of this emerging
      technology.

PMID- 18082919
TI  - Important variables for parents' postnatal sense of security: evaluating a new
      Swedish instrument (the PPSS instrument).
AB  - OBJECTIVE: to evaluate dimensions of both parents' postnatal sense of security
      the first week after childbirth, and to determine associations between the PPSS
      instrument and different sociodemographic and situational background variables.
      DESIGN: evaluative, cross-sectional design. PARTICIPANTS AND SETTINGS: 113
      mothers and 99 fathers with children live born at term, from five hospitals in
      southern Sweden. MEASUREMENTS AND FINDINGS: mothers and fathers had similar
      feelings concerning postnatal sense of security. Of the dimensions in the PPSS
      instrument, a sense of midwives'/nurses' empowering behaviour, a sense of one's
      own general well-being and a sense of the mother's well-being as experienced by
      the father were the most important dimensions for parents' experienced security.
      A sense of affinity within the family (for both parents) and a sense of
      manageable breast feeding (for mothers) were not significantly associated with
      their experienced security. A sense of participation during pregnancy and general
      anxiety were significantly associated background variables for postnatal sense of
      security for both parents. For the mothers, parity and a sense that the father
      was participating during pregnancy were also significantly associated. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: more focus on parents' participation
      during pregnancy as well as midwives'/nurses' empowering behaviour during the
      postnatal period will be beneficial for both parents' postnatal sense of
      security.

PMID- 18082920
TI  - Lower extremity muscle activity during cycling in adolescents with and without
      cerebral palsy.
AB  - BACKGROUND: In individuals with cerebral palsy, adaptation and plasticity in the
      neuromuscular system can lead to detrimental changes affecting gait. Cycling may
      be an effective method to improve mobility. The biomechanics of cycling in
      adolescents with cerebral palsy have been studied, but further analysis of the
      frequency and amplitude characteristics of the electromyographic signals can
      assist with interpretation of the cycling kinematics. METHODS: Data were analyzed
      from 10 adolescents with typical development (mean=14.9, SD=1.4 years) and 10
      adolescents with cerebral palsy (mean=15.6, SD=1.8 years) as they cycled at two
      different cadences. Analyses of the lower extremity electromyographic signals
      involved frequency and amplitude analysis across the cycling revolution.
      FINDINGS: Examination of cycling cadence revealed that adolescents with cerebral
      palsy had altered electromyographic characteristics in comparison to adolescents
      with typical development across the entire crank revolution for all muscles.
      Analyses of individual muscles indicated both inappropriate muscle activation and
      weakness. INTERPRETATION: A more comprehensive analysis of electromyographic
      activity has the potential to provide insight into how a task is accomplished. In
      this study, the control of the several muscles, especially the rectus femoris,
      was significantly different in adolescents with cerebral palsy. This, combined
      with muscle weakness, may have contributed to the observed deviations in joint
      kinematics. Interventions that increase muscle strength with feedback to the
      nervous system about appropriate activation timing may be beneficial to allow
      individuals with cerebral palsy to cycle more efficiently.

PMID- 18082921
TI  - Intraarticular pressure distribution in the talocrural joint is related to lower
      leg muscle forces.
AB  - BACKGROUND: It is of paramount importance to know the magnitude and the
      distribution of joint contact stress within the most heavily loaded structures of
      the human foot. In the talocrural joint role of external loading and loading
      applied by muscles on joint contact stress is not extensively studied. The
      purpose was to determine the distribution of joint contact stress of the
      talocrural joint with varying axial tibia loading and extrinsic tendon loading.
      METHODS: Five cadaveric feet were studied in the intact condition and following
      transsection of ligaments under seventeen different loading conditions. Joint
      contact stress was determined from capacitive pressure sensors implanted in the
      talocrural joint when the specimens were loaded in a specially designed loading
      simulator. Different axial tibia and extrinsic tendon loads were applied. Motions
      of the bony structures were assessed by an optical motion analysis system.
      FINDINGS: The anterior aspect of the joint is predominantly stressed in all
      loading conditions. The influence of muscle force on the internal joint contact
      stress distribution is higher than the axial shank loading. The biggest effect on
      joint contact stress was initiated by the tibialis posterior muscle. The flexor
      hallucis homogenizes the pressure distribution in intact joint conditions. Joint
      angles were not substantially changed by muscle force applications.
      INTERPRETATION: The functions of the muscles of the lower leg are important for
      maintaining physiologic joint contact stress. Reducing the force potentials of
      certain muscle tendon units through surgeries, immobilization, fatigue or
      inappropriate footwear should change the joint contact stress. Such information
      is helpful to understand the physiological function of the foot. It might also
      explain the development and manifestation of certain foot pathologies.

PMID- 18082922
TI  - Effect of increases in plantarflexor and hip flexor muscle strength on the levels
      of effort during gait in individuals with hemiparesis.
AB  - BACKGROUND: Following a stroke, strength gain of the trained affected lower-limb
      muscles has been observed to result in a change in gait speed, but its effect on
      other variables related to gait performance has scarcely been studied. The aim of
      this study was to assess the effect of strength gain of the affected
      plantarflexors and hip flexors on bilateral levels of effort during gait, in the
      sagittal plane of movement. METHODS: The levels of effort of 24 chronic
      hemiparetic participants (mean (standard deviation (SD)): 57.3 (SD 15.5) years),
      who had strength gains in the ankle and hip muscles following a strengthening
      programme, were estimated with the muscular utilization ratio during self
      selected and maximal speeds. The ratio relates the net moment in gait relative to
      the muscle's maximal capability. The peak value and the area under the curve of
      the ratio were used as main outcome measures. FINDINGS: Regardless of speed,
      strength gains have been noted to cause a significant 12-17% decrease in the peak
      value of the ratio of the affected plantarflexors and hip flexors with a
      reduction of the area under the curve of the affected hip flexors' ratio and a
      trend toward a decrease for the affected plantarflexors at maximal speed. A
      significant, albeit small increase in self-selected and maximal gait speeds
      (P<0.05) was also observed post-training. Regardless of assessment time, the peak
      value of the affected plantarflexors' ratio was greater than that of the affected
      hip flexors at self-selected speed (P=0.006) and the area under the curve of the
      affected hip flexors' ratio was greater than that of the affected plantarflexors
      (P=0.007) at maximal speed. Generally, negative associations (-0.32<r>-0.83) were
      noted between the changes in the peak value of the ratio and strength but not
      between the changes in gait speed. INTERPRETATION: The decrease in the peak value
      of the ratio could be explained by the increase in strength. Becoming stronger,
      hemiparetic participants favoured a reduction of their levels of effort during
      walking instead of substantially increasing their gait speed.

PMID- 18082923
TI  - Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the
      green tea polyphenol EGCG.
AB  - Frequent consumption of green tea, one of the most popular and widely consumed
      beverages, has been known to protect against development of various cancers
      according to numerous experimental and several population-based studies.
      Molecular mechanisms underlying chemopreventive effects exerted by green tea and
      its components have been extensively investigated. (-)-Epigallocatechin-3-gallate
      (EGCG), a major green tea polyphenol, has been shown to induce expression of
      glutathione S-transferase, glutathione peroxidase, glutamate cysteine ligase,
      hemeoxygenase-1, etc. that are involved in the elimination or inactivation of
      reactive oxygen species and electrophiles implicated in multi-stage
      carcinogenesis. The redox-sensitive transcription factor, nuclear factor
      erythroid 2 p45 (NF-E2)-related factor (Nrf2) plays a key role in regulating
      induction of phase II detoxifying or antioxidant enzymes. Thus, activation of
      Nrf2 is considered to be an important molecular target of many chemopreventive
      and chemoprotective agents. This review summarizes the molecular basis of
      chemoprevention and cytoprotection afforded by EGCG with emphasis on its ability
      to modulate Nrf2-mediated cellular events.

PMID- 18082924
TI  - Subchronic oral toxicity studies of Se-methylselenocysteine, an organoselenium
      compound for breast cancer prevention.
AB  - Se-methylselenocysteine (MSC) is an organoselenium compound being developed for
      breast cancer chemoprevention. To characterize MSC toxicity, CD rats received
      daily gavage doses of 0, 0.5, 1.0, or 2.0 mg/kg/day (0, 3, 6, or 12 mg/m(2)/day),
      and beagle dogs received daily gavage doses of 0, 0.15, 0.3, or 0.6 mg/kg/day (0,
      3, 6, or 12 mg/m(2)/day) for 28 days. In rats, MSC induced dose-related
      hepatomegaly in both sexes; mild anemia, thrombocytopenia, and elevated liver
      enzymes were observed in high dose females only. Microscopic pathology included
      hepatocellular degeneration (high dose males, all doses in females); arrested
      spermatogenesis (high dose males); and atrophy of corpora lutea (middle and high
      dose females). In dogs, MSC induced mild anemia in middle and high dose males,
      and in high dose females. Toxicologically significant microscopic lesions in dogs
      were seen only in the liver (peliosis and vacuolar degeneration in high dose
      males, midzonal necrosis in males in all dose groups). Based on liver pathology
      seen in female rats in all dose groups, the no observed adverse effect level
      (NOAEL) for MSC in rats is <0.5mg/kg/day. Based on alterations in hematology
      parameters and liver morphology in male dogs in all dose groups, the NOAEL for
      MSC in dogs is <0.15 mg/kg/day.

PMID- 18082925
TI  - Ciglitazone induces caspase-independent apoptosis via p38-dependent AIF nuclear
      translocation in renal epithelial cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists have been
      reported to induce apoptosis in a variety of cell types including renal proximal
      epithelial cells. However, the underlying mechanism of cell death induced by
      PPARgamma agonists has not been clearly defined in renal proximal tubular cells.
      This study was therefore undertaken to determine the mechanism by which
      ciglitazone, a synthetic PPARgamma agonist, induces apoptosis in opossum kidney
      (OK) cells, an established renal epithelial cell line. Ciglitazone treatment
      induced apoptotic cell death in a dose- and time-dependent manner. Ciglitazone
      caused a transient activation of ERK and sustained activation of p38 MAP kinase.
      Ciglitazone-mediated cell death was attenuated by the p38 inhibitor SB203580 and
      transfection of dominant-negative form of p38, but not by the MEK inhibitor
      U0126, indicating that p38 MAP kinase activation is involved in the ciglitazone
      induced cell death. Although ciglitazone-induced caspase-3 activation, the
      ciglitazone-mediated cell death was not affected by the caspase-3 inhibitor DEVD
      CHO. Ciglitazone-induced mitochondrial membrane depolarization and apoptosis
      inducing factor (AIF) nuclear translocation and these effects were prevented by
      the p38 inhibitor. These results suggest that ciglitazone induces caspase
      independent apoptosis through p38 MAP kinase-dependent AIF nuclear translocation
      in OK renal epithelial cells.

PMID- 18082927
TI  - Farmyard point discharges and their influence on nutrient and labile carbon
      dynamics in a second order stream draining through a dairy unit.
AB  - Two small piped sources deriving from a single farmyard together with the
      receiving second order stream above and below the farmyard region were sampled
      over a two-year period. Although not measured directly, observations at the time
      of sampling suggested that maximum drain flow was about 2% of downstream base
      flow. Both point sources were flowing on each sampling occasion (~62) and usually
      had concentrations of phosphorus (P), nitrate (NO(3)-N) and biological oxygen
      demand (BOD) well above those from the upstream site. Individual sample
      concentrations ranged over more than two orders of magnitude for most
      determinants and a large proportion of the total P was present as soluble
      (inorganic and organic) and therefore labile forms. More than 70% of samples
      collected at the downstream site had concentrations that were >1.2 times those of
      the corresponding upstream site. On certain sampling occasions >80% of total
      dissolved phosphorus (TDP) and >90% of the BOD and NO(3) instantaneous load
      appeared to originate from the farmyard region with the composition of downstream
      samples being completely overwhelmed after the passage through the farmyard.
      Extrapolations using instantaneous loads suggest that the farmyard and adjacent
      areas contributed on average 25-30% of the total and dissolved annual downstream
      P load of 3 kg P ha(-1) and 1.7 kg P ha(-1), respectively. There was no clear
      relationship between the relative proportion of the contaminant loading
      originating from the farmyard region and hydrological events. This emphasises the
      potential localised significance that small, highly concentrated, continuous or
      semi-continuous farmyard sources can impact headwater streams during periods of
      low stream flow.

PMID- 18082926
TI  - Endometrial expression of vasopressin, oxytocin and their receptors in patients
      with primary dysmenorrhoea and healthy volunteers at ovulation.
AB  - OBJECTIVE: To investigate gene expressions for neurohypophyseal and ovarian
      hormones as well as their receptors in the endometrium of women with primary
      dysmenorrhoea and healthy subjects at ovulation. STUDY DESIGN: A group of eight
      women with moderate to severe dysmenorrhoea and eight healthy subjects were
      compared in parallel between 18 and 35 years of age, regularly menstruating, non
      overweight and nulliparous. The study was performed at The Department of
      Obstetrics and Gynecology, University Hospital of Lund, Sweden. Endometrial
      biopsies were taken around the time of ovulation, which was determined by
      repeated ultrasound examinations. Receptor and gene expressions for oxytocin and
      vasopressin in the tissue were measured. RESULTS: The gene expression for
      oxytocin receptor was significantly lower in dysmenorrhoic than in healthy women,
      in median 1.21 and 3.44 oxytocin-receptor/actin, respectively (p=0.048). The
      expressions for oxytocin peptide, vasopressin V1a receptor, oestrogen receptor
      alpha, beta and progesterone receptor did not differ between the two groups.
      Expression of vasopressin peptide was not detectable. CONCLUSION: A lower
      oxytocin receptor gene expression at mid-cycle could be involved in the aetiology
      of primary dysmenorrhoea. However, the importance of a paracrine effect of
      oxytocin and its receptor at ovulation warrants further investigation.

PMID- 18082928
TI  - Legalizing markets and the consequences for poaching of wildlife species: the
      vicuna as a case study.
AB  - Vicuna provide an excellent case study for examining the sustainable use of
      wildlife outside protected areas: the community-based conservation approach.
      Vicuna populations in the high Andes of Argentina, Bolivia, Chile, Ecuador and
      Peru fell to a critically low level, but a Convention on International Trade in
      Endangered Species of Wild Fauna and Flora (CITES) ban on trade in their fiber
      has seen numbers recover dramatically, and now live shearing of vicuna for a high
      value international market is being promoted as a mechanism to secure both
      sustainable vicuna populations and local livelihoods. We used a dynamic
      optimization model to explore the consequences of legalizing markets, including
      the consequences for poaching which is critical in vicuna dynamics. Using
      parameters obtained from the literature and expert knowledge, we explored
      different scenarios for the Argentine region of Cieneguillas. Our results showed
      that the role of the international market is ambiguous; live shearing for an
      international market can provide the very best of outcomes for both vicuna and
      local people, with large herds generating high revenues. But an international
      market also creates a market for poached vicuna fiber; as a result, vicuna
      numbers risk once again falling to critically low levels, resulting also in
      minimal revenues from sale of fiber. The message for the international community
      is that if community-based conservation is not implemented carefully then its
      impact can easily be perverse.

PMID- 18082929
TI  - Quantitative catchment profiling to apportion faecal indicator organism budgets
      for the Ribble system, the UK's sentinel drainage basin for Water Framework
      Directive research.
AB  - Under the EU Water Framework Directive (WFD) 20/60/EC and the US Federal Water
      Pollution Control Act 2002 management of water quality within river drainage
      basins has shifted from traditional point-source control to a holistic approach
      whereby the overall contribution of point and diffuse sources of pollutants has
      to be considered. Consequently, there is a requirement to undertake source
      apportionment studies of pollutant fluxes within catchments. The inclusion of the
      Bathing Water Directive (BWD), under the list of 'protected areas' in the WFD
      places a requirement to control sources of faecal indicator organisms within
      catchments in order to achieve the objectives of both the BWD (and its revision -
      2006/7/EC) and the WFD. This study was therefore initiated to quantify catchment
      derived fluxes of faecal indicator compliance parameters originating from both
      point and diffuse sources. The Ribble drainage basin is the single UK sentinel
      WFD research catchment and discharges to the south of the Fylde coast, which
      includes a number of high profile, historically non-compliant, bathing waters.
      Faecal indicator concentrations (faecal coliform concentrations are reported
      herein) were measured at 41 riverine locations, the 15 largest wastewater
      treatment works (WwTWs) and 15 combined sewer overflows (CSOs) across the Ribble
      basin over a 44-day period during the 2002 bathing season. The sampling programme
      included targeting rainfall-induced high flow events and sample results were
      categorised as either base flow or high flow. At the riverine sites, geometric
      mean faecal coliform concentrations showed statistically significant elevation at
      high flow compared to base flow. The resultant faecal coliform flux estimates
      revealed that over 90% of the total organism load to the Ribble Estuary was
      discharged by sewage related sources during high flow events. These sewage
      sources were largely related to the urban areas to the south and east of the
      Ribble basin, with over half the load associated with the relatively small
      subcatchment of the River Douglas. The majority of this load was attributed to
      two WwTWs that discharge through a common outfall close to the tidal limit of
      this catchment. Budgets adjusted to accommodate the impact of proposed UV
      disinfection of these effluents showed that the load from these sources would be
      reduced significantly during base flow conditions. However, during high flow
      events loads would still remain high due to the operation of storm sewage
      overflows from stormwater retention tanks. The study identified untreated storm
      sewage spills from urban infrastructure and WwTW stormwater retention tanks as
      the dominant component of the high flow flux of faecal indicators to receiving
      waters of the Fylde coast and the associated bathing waters.

PMID- 18082930
TI  - Costs of the electrochemical oxidation of wastewaters: a comparison with
      ozonation and Fenton oxidation processes.
AB  - In the work described here the technical and economic feasibilities of three
      Advanced Oxidation Processes (AOPs) have been studied: Conductive-Diamond
      Electrochemical Oxidation (CDEO), Ozonation and Fenton oxidation. The comparison
      was made by assessing the three technologies with synthetic wastewaters polluted
      with different types of organic compounds and also with actual wastes (from olive
      oil mills and from a fine-chemical manufacturing plant). All three technologies
      were able to treat the wastes, but very different results were obtained in terms
      of efficiency and mineralization. Only CDEO could achieve complete mineralization
      of the pollutants for all the wastes. However, the efficiencies were found to
      depend on the concentration of pollutant (mass transfer control of the oxidation
      rate). Results obtained in the oxidation with ozone (at pH 12) or by Fenton's
      reagent were found to depend on the nature of the pollutants, and significant
      concentrations of oxidation-refractory compounds were usually accumulated during
      the treatment. Within the discharge limits that all of the technologies can
      reach, the economic analysis shows that the operating cost of Fenton oxidation is
      lower than either CDEO or ozonation, although CD?EO can compete satisfactorily
      with the Fenton process in the treatment of several kinds of wastes. Likewise,
      the investment cost for the ozonation process seems to be higher than either CDEO
      or Fenton oxidation, regardless of the pollutant treated.

PMID- 18082931
TI  - The microbial status of natural waters in a protected wilderness area.
AB  - Waters derived from remote 'wilderness' locations have been assumed to be largely
      free of bacterial contamination and thus such, near-pristine, protected
      catchments, unused for agriculture, have been first in the multiple line of
      protection (pristine catchment-long storage-treatment-disinfection) employed by
      the water industry. This assumption is challenged by a bacterial survey of the
      waters derived from the New Cairngorm National Park, Scotland. Over 480 spot
      samples were taken for 59 sites between March 2001 and October 2002 during nine
      field campaigns each of three to five days duration. Over 75% of samples tested
      positive for Escherichia coli (E. coli) and 85% for total coliforms.
      Concentrations displayed both temporal and spatial patterns. Largest values
      occurred over the summer months and particularly at weekends at sites frequented
      by visitors, either for 'wild' camping or day visits, or where water was drawn
      from the river for drinking. Overall the spatial and temporal variations in
      bacterial concentrations suggest a relationship with visitor numbers and in
      particular wild camping. The implications of the results for drinking water
      quality and visitors health are discussed along with possible management options
      for the area in terms of improving the disposal of human waste.

PMID- 18082932
TI  - Editorial comment on: the value of the UroVysion assay for surveillance of non
      muscle-invasive bladder cancer.

PMID- 18082933
TI  - Editorial comment on: the value of the UroVysion assay for surveillance of non
      muscle-invasive bladder cancer.

PMID- 18082934
TI  - The value of the UroVysion assay for surveillance of non-muscle-invasive bladder
      cancer.
AB  - OBJECTIVE: Patients with non-muscle-invasive bladder cancer are traditionally
      followed by repeat cystoscopy and urine cytology. A fluorescence in situ
      hybridisation technique called UroVysion (UV) is now available for clinical
      diagnosis of urothelial cancer cells. The aim of the present study was to compare
      UV analysis with routine follow-up methods. METHODS: We studied an unselected
      cohort of patients undergoing cystoscopy follow-ups at two Swedish centres in
      2004-2005. All patients were investigated by cystoscopy, cytology, and UV assay.
      The UV assay was evaluated with regards to sensitivity, specificity, and positive
      predictive value for tumour recurrence. RESULTS: In all, 159 cases were analysed.
      UV had a 30% overall sensitivity for the 27 biopsy-proven recurrences and 70%
      sensitivity for high-risk tumours (pT1 and carcinoma in situ [CIS]). The
      specificity of UV was 95%. UV detected all six CIS cases in the study and was
      predictive in two additional patients who developed CIS within 1 yr of inclusion.
      Cytology was positive in four of those eight CIS cases and atypical in the other
      four. CONCLUSIONS: The UV assay cannot replace cystoscopy for surveillance of
      patients with non-muscle-invasive bladder cancer, but it may be valuable as a
      supplement to traditional measures for detecting CIS. Before any conclusions can
      be drawn regarding the efficacy of novel markers of bladder cancer, they must be
      studied in bladder cancer patients undergoing endoscopic surveillance.

PMID- 18082935
TI  - Comparison of metabolite production capability indices generated by network
      analysis methods.
AB  - A framework of constraint-based reconstruction and analysis (COBRA) is used for
      modeling large-scale metabolic networks. In COBRA, extreme pathway and
      optimization analyses are commonly used to study the properties of networks.
      While the results of both methods are completely consistent, extreme pathway
      analysis is considered to be better because of its wider representational
      ability. In this study, we assessed these two methods by computational knockout
      experiments. We examined a simple pathway model and found that the extreme
      pathway method led to misguided conclusions in specific cases, while optimization
      analysis calculated the correct knockout effects. We also investigated the
      Escherichia coli metabolic pathway model, and found that these methods result in
      inconsistent interpretations of the network properties. IN CONCLUSION: it has
      been claimed that these two methods result in the same producible metabolites,
      but we found a difference in individual results for a biological pathway. Our
      results could provide helpful guidance for when to use the methods, particularly
      extreme pathway analysis.

PMID- 18082936
TI  - Evolutionary modelling of feed forward loops in gene regulatory networks.
AB  - Feed forward loops (FFLs) are gene regulatory network motifs. They exist in
      different types, defined by the signs of the effects of genes in the motif on one
      another. We examine 36 feed forward loops in Escherichia coli, using evolutionary
      simulations to predict the forms of FFL expected to evolve to generate the
      pattern of expression of the output gene. These predictions are tested using
      likelihood ratios, comparing likelihoods of the observed FFL structures with
      their likelihoods under null models. The very high likelihood ratios generated,
      of over 10(11), suggest that evolutionary simulation is a valuable component in
      the explanation of FFL structure.

PMID- 18082937
TI  - Importance of UDP-glucuronosyltransferase 1A1*6 for irinotecan toxicities in
      Japanese cancer patients.
AB  - Recent pharmacogenetic studies on irinotecan have revealed the impact of UDP
      glucuronosyltransferase (UGT) 1A1*28 on severe irinotecan toxicities. Although
      the clinical role of UGT1A1*6, which is specifically detected in East Asian
      patients, in irinotecan toxicities is suggested, clear evidence remains limited.
      To examine the impact of *6, the association of UGT1A1 genotypes with severe
      irinotecan toxicities was retrospectively investigated in Japanese cancer
      patients. A significant *6-dependent increase in the incidence of grade 3 or 4
      neutropenia was observed in 49 patients on irinotecan monotherapy (p=0.012). This
      study further clarifies the clinical importance of *6 in irinotecan therapy in
      East Asians.

PMID- 18082938
TI  - Multipoint quantification of multimarker genes in peripheral blood and
      micrometastasis characteristic in peri-operative esophageal cancer patients.
AB  - This work proposed a method to assess the occult micrometastasis characteristic
      in peri-operative peripheral blood (PB) based on multipoint quantification of
      multimarker genes by real-time semiquantitative RT-PCR. The expression levels of
      SCC, CK19, CK20, CEA and survivin mRNA in PB samples collected before surgery (B
      1), immediately after surgery (B0) and at the third day post-operatively (B+3)
      from 36 squamous esophageal cancer (EC) patients were detected. SCC and CK19 mRNA
      showed low positivity detection rates, while the rate for CEA and survivin mRNA
      panel was 58.3%, 83.3% and 72.3% at B-1, B0 and B+3, respectively. Opposite to
      the significant increase and slow decrease of CEA cells at stages of B-1 to B0
      and B0 to B+3, respectively, survivin cells decreased significantly and increased
      quickly at the two stages. The follow-up with a period of 1.2 years showed that
      the patients with the B+3/B0 ratios of >or= 0.3 for CEA cells or/and >or= 10 for
      survivin cells exhibited significantly high possibility of developed metastasis,
      and the sensitivity to predict developed metastasis increased from 54.5% of CEA
      mRNA alone to 72.7% of CEA and survivin mRNA panel. These results suggested that
      CEA and survivin gene panel improved the sensitivity to predict recurrence and
      differentiate the micrometastatic process.

PMID- 18082939
TI  - Metabolism of resveratrol in breast cancer cell lines: impact of sulfotransferase
      1A1 expression on cell growth inhibition.
AB  - Resveratrol is a polyphenolic compound present in grapes and wine with anticancer
      activities that undergoes pronounced metabolism in humans. In order to determine
      whether metabolism of resveratrol also occurs in tumor cells and whether
      biotransformation has any impact on cytotoxicity, metabolism experiments were
      conducted with hormone-dependent ZR-75-1 and hormone-independent MB-MDA-231 human
      breast cancer cells. Along with resveratrol, it was possible to identify one
      metabolite, namely, resveratrol-3-O-sulfate in both cell lines. Its concentration
      in the cytoplasm and culture medium was 5.4- to 9-fold higher in ZR-75-1 cells
      than in MDA-MB-231 cells, concomitant with a 3.1-fold higher IC(50) value in the
      ZR-75-1 cell line (74 microM compared to 38 microM). By using RT-PCR, expression
      of sulfotransferase (SULT)1A1 mRNA, but not of other SULTs investigated, showed a
      close correlation with resveratrol 3-O-sulfate formation which was particularly
      high in ZR-75-1 and very low in MDA-MD-231 cells. In conclusion, we demonstrate
      that SULT1A1-based biotransformation reduces the anticancer activity of
      resveratrol in breast cancer cells, which must be considered in humans following
      oral uptake of dietary resveratrol as a chemopreventive agent.

PMID- 18082940
TI  - Polyphyllin D induces mitochondrial fragmentation and acts directly on the
      mitochondria to induce apoptosis in drug-resistant HepG2 cells.
AB  - We previously showed that polyphyllin D (PD) produced a stronger apoptotic effect
      in R-HepG2 with multi-drug resistance (MDR) than that in its parent HepG2 cells
      without MDR. In this study, PD was found to elicit mitochondrial fragmentation in
      live cells by using total internal reflection fluorescence microscopy (TIRFM).
      When mitochondria were isolated and treated directly with PD, a stronger
      swelling, deeper transmembrane depolarization, and more apoptosis-inducing factor
      (AIF) release were observed from the mitochondria of R-HepG2 than that of HepG2.
      These observations suggest that PD is a potent anti-cancer agent that bypasses
      MDR and elicits apoptosis via mitochondrial injury.

PMID- 18082941
TI  - Rapid screening of antineoplastic candidates for the human organic anion
      transporter OATP1B3 substrates using fluorescent probes.
AB  - A rapid screening system has been established to extract novel candidates that
      exhibit potent inhibition of the transport of fluorescent substrate by organic
      anion transporting polypeptide (OATP) 1B3. OATP1B3 is abundantly expressed in
      solid digestive organ cancers. Thus, the identification of new substrates leads
      to novel strategies for effective cancer chemotherapy with minimal adverse
      effects. We used an automated image acquisition and analysis system (IN Cell
      Analyzer 1000) to visualize the transport and subsequent accumulation of the
      fluorescent substrate chenodeoxycholyl-(Nepsilon-NBD)-lysine (CDCA-NBD).
      Antineoplastic screening demonstrated that five candidates agents, docetaxel,
      actinomycin D, mitoxantrone, paclitaxel, and SN-38, exhibited potent inhibitory
      effects on OATP1B3-mediated transport of CDCA-NBD. To clarify if these
      antineoplastic drugs are substrates for OATP1B3, we performed transport assays in
      OATP1B3-expressing cells. We determined that SN-38 is a novel substrate for
      OATP1B3. In conclusion, our results demonstrate that the screening system
      established in this study is a useful method for the rapid extraction of
      candidate therapeutic agents from the large numbers of compounds.

PMID- 18082942
TI  - Treatment of the baker's yeast wastewater by electrocoagulation.
AB  - In the laboratory-scale experiments, treatment of baker's yeast production
      wastewater has been investigated by electrocoagulation (EC) using a batch
      reactor. Effects of the process variables such as pH, electrode material (Fe and
      Al), current density, and operating time are investigated in terms of removal
      efficiencies of chemical oxygen demand (COD), total organic carbon (TOC),
      turbidity, and operating cost, respectively. The maximum removal efficiencies of
      COD, TOC and turbidity under optimal operating conditions, i.e., pH 6.5 for Al
      electrode and pH 7 for Fe electrode, current density of 70 A/m2 and operating
      time of 50 min were 71, 53 and 90% for Al electrode and 69, 52 and 56% for Fe
      electrode, respectively. Al electrode gave 4.4 times higher removal efficiency of
      turbidity than Fe electrode due to interference from color of dissolved iron. The
      operating costs for Al and Fe electrodes in terms of $/m3 or $/kg COD were 1.54
      and 0.82, 0.51 and 0.27, respectively.

PMID- 18082943
TI  - Degradation of diuron in aqueous solution by dielectric barrier discharge.
AB  - Degradation of diuron in aqueous solution was conducted in a dielectric barrier
      discharge (DBD) reactor and the proposed degradation mechanism was investigated
      in detail. The factors that affect the degradation of diuron were examined. The
      degradation efficiency of diuron and the removal of total organic carbon (TOC)
      increased with increasing input power, and the degradation of diuron by DBD
      fitted first-order kinetics. Both strong acidic and alkaline solution conditions
      could improve diuron degradation efficiency and TOC removal rate. Degradation of
      diuron could be accelerated or inhibited in the presence of H2O2 depending on the
      dosage. The degradation efficiency increased dramatically with adding Fe2+. The
      removal of TOC and the amount of the detected Cl-, NO3- and NH4+ were increased
      in the presence of Fe2+. The concentrations of oxalic and acetic acids were
      almost the same in the absence and presence of Fe2+, but high concentration of
      formic acid was accumulated in the presence of Fe2+. The main degradation pathway
      of diuron by DBD involved a series of dechlorination-hydroxylation, dealkylation
      and oxidative opening of the aromatic ring processes.

PMID- 18082944
TI  - Multi-component sorption of Pb(II), Cu(II) and Zn(II) onto low-cost mineral
      adsorbent.
AB  - Multi-component sorption studies were carried out for attenuation of divalent
      heavy metal cations (Pb2+, Cu2+ and Zn2+) by a low-cost mineral adsorbent from
      the aqueous solution. Kinetic and equilibrium batch-type sorption experiments
      were conducted under variable conditions for multi-component using low-grade
      (<12%P2O5) phosphate rock. Percentage of multiple heavy metal species removal
      increases with decreasing initial metals concentration and particle size. The
      equilibrium data were well described to a lesser extent by Freundlich model but
      Langmuir model seemed to be more appropriate with the fixation capacity obtained
      at room temperature for Pb2+, Cu2+ and Zn2+ was 227.2, 769.2 and 666.6 micromol
      g(-1), respectively. Two simple kinetic models were tested to investigate the
      adsorption mechanism. Rate constants have been found nearly constant at all metal
      concentrations for first order. The comparison of adsorption capacity of low
      grade phosphate rock decreases in multi-component system as compared to single
      component due to ionic interactions. X-ray powder diffraction (XRPD) technique
      was used to ascertain the formation of new metal phases followed by surface
      complexation. Used adsorbents have been converted into a value added product by
      utilizing innovative Zero-waste concept to solve the used adsorbents disposal
      problem and thus protecting the environment.

PMID- 18082945
TI  - Effects of carbonate and organic matter on sorption and desorption behavior of
      polycyclic aromatic hydrocarbons in the sediments from Yangtze River.
AB  - The role of carbonate and organic matter in the sorption and desorption process
      of polycyclic aromatic hydrocarbons (PAHs) was studied by using a sequential
      separation procedure, which sequentially removed carbonate and organic matter
      from the natural sediment. Five PAHs were used as multi-sorbate and their
      sorption and desorption characteristics in separated samples were investigated.
      The Linear, Freundlich and Langmuir models were applied to correlate the
      experimental data to reveal sorption characteristics of PAHs. The results showed
      that the sorption mechanism was neither complete adsorption nor partition
      procedure. The desorption mass of PAHs was very low for all the three sediment
      samples, especially for higher ring PAHs. It was discovered that carbonate mainly
      affected sorption and desorption process of lower ring PAHs due to its influence
      on the physical characteristics of sediment. Organic matter remarkably affected
      the behavior of higher ring PAHs in the sorption and desorption procedure by
      determining the dominating partition process.

PMID- 18082946
TI  - Effects of inoculation of biosurfactant-producing Bacillus sp. J119 on plant
      growth and cadmium uptake in a cadmium-amended soil.
AB  - A biosurfactant-producing Bacillus sp. J119 isolated from heavy metal
      contaminated soils was investigated for its effects on the plant growth-promoting
      characteristics and heavy metal and antibiotic resistance. A pot experiment was
      conducted for investigating the capability of the biosurfactant-producing
      bacterial strain Bacillus sp. J119 to promote the plant growth and cadmium uptake
      of rape, maize, sudangrass and tomato in soil artificially contaminated with
      different levels of cadmium (Cd) (0 and 50mgkg(-1)). The strain was found to
      exhibit different multiple heavy metal (Pb, Cd, Cu, Ni and Zn) and antibiotic
      (kanamycin, streptomycin, ampicillin, tetracycline and rifampin) resistance
      characteristics. The strain had the capacity to produce indole acetic acid (IAA)
      and siderophores. Cd treatment did not significantly decreased growth of tomato,
      maize and rape plants, but Cd treatment significantly decreased growth of
      sudangrass (p<0.05). In the Cd-added soil, above-ground biomass and root dry
      weights of tomatoes were increased by 24 and 59%, respectively, in live bacterial
      inoculation compared to dead bacterial inoculation control. There were no obvious
      differences in the above-ground tissue and root dry weight of maize and
      sudangrass between live bacterial inoculation and dead bacterial inoculation. In
      the soil treated with 50 mg Cdkg(-1), increase in above-ground tissue Cd content
      varied from 39 to 70% in live bacterium-inoculated plants compared to dead
      bacterium-inoculated control. In addition, among the inoculated plants, tomato
      was the greatest Cd accumulator. The bacterial strain was also able to colonize
      and develop in the rhizosphere soils after root inoculation.

PMID- 18082947
TI  - Degradation of bisphenol A and formation of hydrogen peroxide induced by glow
      discharge plasma in aqueous solutions.
AB  - Degradation of bisphenol A (BPA) and simultaneous formation of hydrogen peroxide
      induced by glow discharge plasma in contact with aqueous solution were
      investigated. Experimental results indicated that the BPA degradation rate was
      higher in sodium chloride solution than that in sodium sulfate or phosphate
      solutions. However, the formation rates of hydrogen peroxide were on the opposite
      case. Both the BPA removal and the hydrogen peroxide production rates decreased
      in the presence of hydroxyl radical scavengers, indicating that hydroxyl radicals
      are the most probable oxidants responsible for BPA degradation and the precursors
      of hydrogen peroxide. Ferric ion showed better catalytic effect than that of
      ferrous ion, suggesting that the ferric ion was reduced by the intermediates
      formed during BPA degradation, which was confirmed by following the production of
      ferrous ion in the system. TOC of the solution gradually reduced with discharge
      time; however, without catalysts, the solution COD increased with discharge time
      and sharply decreased in the presence of iron salts. The major intermediate
      products were identified by LC/MS and the possible degradation mechanism was
      discussed.

PMID- 18082948
TI  - Mechanism of p-nitrophenol adsorption from aqueous solution by HDTMA+-pillared
      montmorillonite--implications for water purification.
AB  - HDTMA+-pillared montmorillonites were obtained by pillaring different amounts of
      the surfactant hexadecyltrimethylammonium bromide (HDTMAB) into sodium
      montmorillonite (Na-Mt) in an aqueous solution. The optimum conditions and batch
      kinetics of sorption of p-nitrophenol from aqueous solutions are reported. The
      solution pH had a very important effect on the sorption of p-nitrophenol. The
      maximum p-nitrophenol absorption/adsorption occurs when solution pH (7.15-7.35)
      is approximately equal to the pKa (7.16) of the p-nitrophenol ion deprotonation
      reaction. X-ray diffraction analysis showed that surfactant cations had been
      pillared into the interlayer and the p-nitrophenol affected the arrangement of
      surfactant. With the increased concentration of surfactant cations, the
      arrangement of HDTMA+ within the clay interlayer changes and the sorption of p
      nitrophenol increases. HDTMA+-pillared montmorillonites are more effective than
      Na-Mt for the adsorption of p-nitrophenol from aqueous solutions. The Langmuir,
      Freundlich and dual-mode sorption were tested to fit the sorption isotherms.

PMID- 18082949
TI  - Speciation of heavy metals in sediment by conventional, ultrasound and microwave
      assisted single extraction methods: a comparison with modified sequential
      extraction procedure.
AB  - Sequential extraction procedure proposed by the European Standards, Measurements
      and Testing (SM&T) Program, formerly the Community Bureau of Reference (BCR), has
      been applied for the heavy metals (HMs) partitioning in fresh water lake sediment
      samples. The results obtained by conventional sequential extraction BCR method
      (SEB) for Cd, Cu, Cr, Ni, Pb and Zn were compared with those estimated from three
      alternative single extractions, conventional (CSE), ultrasonic (USE) and
      microwave assisted (MSE), using identical operating conditions applied in each
      individual BCR fraction and validated by the CRM BCR 701. Extractable HMs
      contents obtained by all compared methodologies were measured by atomic
      absorption spectrometery. With the use of compromised sonication and microwave
      conditions, steps 1-3 of the sequential extraction (excluding the hydrogen
      peroxide digestion in step 3) could be completed between 15-30 min using
      ultrasonic bath, while 60-120 s were required for MSE. The total extractable
      metal contents obtained by three single extractions ranged from 75.1% to 114.0%
      except Cr in first step, which was extracted (125.3%) by MSE method as compared
      to those obtained by SEB procedure. The precision of the proposed BCR single
      extraction methods (expressed as RSD%) was found in the range of (3.99-9.6%) for
      all metals.

PMID- 18082950
TI  - Temporal variability of benzene concentration in the ambient air of Delhi: a
      comparative assessment of pre- and post-CNG periods.
AB  - CNG (compressed natural gas) was fully implemented in public transport system in
      Delhi in December 2002. The study assesses the benzene concentration trends at
      two busy traffic intersections and a background site in Delhi, India. Monitoring
      was done for two different time periods viz; in the year 2001-2002 (pre-CNG) and
      two winter months (January and February) of the year 2007 (post-CNG) to assess
      the impact of various policy measures adopted by the government of Delhi to
      improve the air quality in the city. Annual average benzene concentration for the
      pre-CNG period was found to be 86.47+/-53.24 microg m(-3). Average benzene
      concentrations for the winter months (January-February) of pre- and post-CNG
      periods were 116.32+/-51.65 microg m(-3) and 187.49+/-22.50 microg m(-3),
      respectively. Enhanced values could be solely attributed to the increase in the
      vehicular population from 3.5 million in the year 2001-2002 to approximately 5.1
      millions in the year 2007.

PMID- 18082951
TI  - New methodology for hazardous waste classification using fuzzy set theory Part I.
      Knowledge acquisition.
AB  - In the literature on hazardous waste classification, the criteria used are mostly
      based on physical properties, such as quantity (weight), form (solids, liquid,
      aqueous or gaseous), the type of processes generating them, or a set of
      predefined lists. Such classification criteria are inherently inadequate to
      account for the influence of toxic and hazard characteristics of the constituent
      chemicals in the wastes, as well as their exposure potency in multimedia
      environments, terrestrial mammals and other biota. Second, none of these
      algorithms in the literature has explicitly presented waste classification by
      examining the contribution of individual constituent components of the composite
      wastes. In this two-part paper, we propose a new automated algorithm for waste
      classification that takes into account physicochemical and toxicity effects of
      the constituent chemicals to humans and ecosystems, in addition, to the exposure
      potency and waste quantity. In part I, available data on the physicochemical and
      toxicity properties of individual chemicals in humans and ecosystems, their
      exposure potency in environmental systems and the effect of waste quantity are
      described, because they fundamentally contribute to the final waste ranking.
      Knowledge acquisition in this study was accomplished through the extensive review
      of published and specialized literature to establish facts necessary for the
      development of fuzzy rule-bases. Owing to the uncertainty and imprecision of
      various forms of data (both quantitative and qualitative) essential for waste
      classification, and the complexity resulting from knowledge incompleteness, the
      use of fuzzy set theory for the aggregation and computation of waste
      classification ranking index is proposed. A computer-aided intelligent decision
      tool is described in part II of this paper and the functionality of the fuzzy
      waste classification algorithm is illustrated through nine worked examples.

PMID- 18082952
TI  - Pyridine sorption from aqueous solution by rice husk ash (RHA) and granular
      activated carbon (GAC): parametric, kinetic, equilibrium and thermodynamic
      aspects.
AB  - The present study deals with the adsorption of pyridine (Py) from synthetic
      aqueous solutions by rice husk ash (RHA) and commercial grade granular activated
      carbon (GAC) and reports on the kinetic, equilibrium and thermodynamic aspects of
      Py sorption. Batch sorption studies were carried out to evaluate the effect of
      various parameters, such as adsorbent dose (m), initial pH (pH0), contact time
      (t), initial concentration (C0) and temperature (T) on the removal of Py. The
      maximum removal of Py is found to be approximately 96% and approximately 97% at
      lower concentrations (<50 mg dm(-3)) and approximately 79.5% and approximately
      84% at higher concentrations (600 mg dm(-3)) using 50 kg m(-3) and 30 kg m(-3) of
      RHA and GAC dosage, respectively, at 30+/-1 degrees C. Adsorption of Py is found
      to be endothermic in nature and the equilibrium data can be adequately
      represented by Toth and Redlich-Peterson isotherm equations. Py can be recovered
      from the spent adsorbents by using acidic water and 0.1 N H2SO4. The overall
      adsorption of Py on RHA and GAC is found to be in the order of GAC>RHA.
      Comparative assessment of adsorbents used by various investigators available in
      literature showed the effectiveness of BFA and RHA over other adsorbents. Spent
      RHA can simply be filtered, dried and used in the boiler furnaces/incinerators.
      Thus, its heating value can be recovered.

PMID- 18082953
TI  - Preparation and characterization of magnetically separable photocatalyst
      (TiO2/SiO2/Fe3O4): effect of carbon coating and calcination temperature.
AB  - TiO2/SiO2/Fe3O4 composite was synthesized by sol-gel technique for silica and
      titania coatings on magnetite core to enable recovery after photocatalytic
      degradation. Carbon coating was also carried out by calcination of
      TiO2/SiO2/Fe3O4 under nitrogen atmosphere in presence of PVA as a source of
      carbon to enhance the adsorption of organic compounds on catalyst surface and to
      get better activity. All prepared samples were characterized using EDX, CN
      analyzer, XRD, BET and SEM. Degradation of methyl orange dye was used to assess
      the photocatalytic performance of the prepared samples. Calcination temperature
      was found to affect rate of reaction because of the formation of rutile phase at
      high calcination temperature. Carbon coated samples unexpectedly exhibited lower
      rate of reaction at almost all calcination temperatures.

PMID- 18082954
TI  - Photodegradation of methyl tert-butyl ether (MTBE) by UV/H2O2 and UV/TiO2.
AB  - Two UV-based advanced oxidation processes (AOPs), UV/H2O2 and UV/TiO2, were
      tested in batch reactor systems to evaluate the removal efficiencies and optimal
      conditions for the photodegradation of methyl tert-butyl ether (MTBE). The
      optimal conditions at an initial MTBE concentration of 1 mM ([MTBE]0=1 mM) were
      acidic and 15 mM H2O2 in UV/H2O2 system, and pH 3.0 and 2.0 g/l TiO2 in UV/TiO2
      suspended slurries system under 254-nm UV irradiation. Under the optimal
      conditions, MTBE photodegradation during the initial period of 60 min in UV/H2O2
      and UV/TiO2 systems reached 98 and 80%, respectively. In both systems, MTBE
      photodegradation decreased with increasing [MTBE]0. While MTBE photodegradation
      rates increased with increasing dosage of H2O2 (5-15 mM) and TiO2 (0.5-3 g/l),
      further increase in the dosage of H2O2 (20 mM) or TiO2 (4 g/l) adversely reduced
      the MTBE photodegradation. Pseudo first-order kinetics with regard to [MTBE] can
      be used to describe the MTBE photodegradation in both systems. The pseudo first
      order rate constants linearly increased with the increase in the molar ratio of
      [H2O2]0 to [MTBE]0 in UV/H2O2 system and linearly increased with the decrease in
      [MTBE]0 in UV/TiO2 system.

PMID- 18082955
TI  - Equilibrium, thermodynamic and kinetic studies for the biosorption of aqueous
      lead(II), cadmium(II) and nickel(II) ions on Spirulina platensis.
AB  - The biosorption of lead(II), cadmium(II) and nickel(II) ions from aqueous
      solution by Spirulina platensis was studied as a function of time, concentration,
      temperature, repetitive reactivity, and ionic competition. The kinetic results
      obeyed well the pseudo second-order model. Freundlich, Dubinin Radushkevich and
      Temkin isotherm models were applied in describing the equilibrium partition of
      the ions. Freundlich isotherm was applied to describe the design of a single
      stage batch sorption system. According to the thermodynamic parameters such as
      DeltaG degrees, DeltaH degrees and DeltaS degrees calculated, the sorption
      process was endothermic and largely driven towards the products. Sorption
      activities in a three metal ion system were studied which indicated that there is
      a relative selectivity of the biosorbent towards Pb2+ ions. The measurements of
      the repetitive reusability of S. platensis indicated a large capacity towards the
      three metal ions.

PMID- 18082956
TI  - The mTPH2 C1473G single nucleotide polymorphism is not responsible for
      behavioural differences between mouse strains.
AB  - Tryptophan hydroxylase 2 (TPH2) is the rate limiting enzyme of serotonin
      synthesis in the brain. A recently described functional (C1473G) single
      nucleotide polymorphism in mouse TPH2 resulting in vitro in a strongly decreased
      enzymatic activity was suspected to be responsible for the observed differences
      in 5-HT levels and behaviour between mice strains. We bred two substrains of
      C57BL/6 mice carrying the two isoforms and could show that both exhibit equal TPH
      activity, brain 5-HT content and behaviour. These data indicate that the distinct
      behavioural characteristics of mouse strains are not due to differences in TPH2
      activity, but to other variations in the genetic background.

PMID- 18082957
TI  - An event-related brain potential study of children's conservation.
AB  - To investigate the relationship between cortical activation and conservation
      ability, 22 children were divided into two groups based on their performance on a
      standard Piagetian Conservation test. Visual evoked potentials were recorded
      while children performed a weight conservation task. A bilateral, frontal
      distributed, broad late positive component at 900 ms differed between non
      conserving and conserving children, with non-conservers having a larger
      amplitude. The significant interaction between conservation ability and
      hemisphere on the amplitude of this component suggests that inferior generators
      gradually move from central to right frontal-central while conservation level
      increases. The results indicate the existence of an ERP component that reflects
      weight conservation ability in children and a possible relationship between
      conservation ability and brain activation.

PMID- 18082958
TI  - Low-back-pain related disability: an integration of psychological risk factors
      into the stress process model.
AB  - The purpose of this study was to verify the usefulness of an adaptation of the
      stress process model in organizing the psychological variables associated with
      the development of low-back-pain related disability. French-speaking Canadian
      workers on compensated sick leave (N=439) due to recent occupational low back
      pain (LBP) were evaluated during the sub-acute stage of LBP (between 30 and 83
      days after injury). They were assessed for the following factors: life events,
      injury-specific cognitive appraisal, emotional distress, avoidance coping, and
      functional disability. Confirmatory factor analyses were used to test and modify
      the measurement model. An important modification in the measurement model was the
      association of catastrophizing with the emotional distress factor. During the sub
      acute stage, path analyses revealed a satisfactory fit of the following model
      (the following coefficients are standardized): (a) life events (.30) and
      cognitive appraisal (.42) explained emotional distress (r(2)=.30); (b) emotional
      distress (.42) and cognitive appraisal (.36) explained the use of avoidance
      coping (r(2)=.45); and (c) emotional distress (.24) and avoidance coping (.56)
      explained functional disability (r(2)=.53). The stress model tested here
      reaffirms the importance of life events in the development of disability through
      the more established emotional distress factor. Also, cognitive appraisal appears
      to have an indirect effect on disability through activity avoidance and distress.
      This adaptation of the stress model makes it possible to integrate risk factors
      into a reduced set of meaningful factors and proposes a more general adaptation
      explanation of disability than the specific fear-avoidance model.

PMID- 18082959
TI  - Pedicled flaps are first choice in the reconstruction of hot air sauna burns.

PMID- 18082960
TI  - Spray on skin improves psychosocial functioning in pediatric burns patients: a
      randomized controlled trial.
AB  - PURPOSE: Microskin is a sprayed on, computer color-matched, skin camouflage which
      can last for up to 5 days after application. It binds to the epidermis and the
      patient can sweat and swim with it on. The purpose of the current study was to
      determine whether Microskin produces psychosocial benefit in pediatric burns
      patients. PROCEDURE: Twenty children with mature burn scars took part in the
      study and used Microskin for 5 weeks. Initially, 10 children were randomized to a
      treatment group while the remaining 10 became a wait-list group for 7 weeks. The
      wait-list group subsequently received Microskin for 5 weeks. Before and after
      using Microskin, children completed three psychosocial measures; the Strengths
      and Difficulties Questionnaire (SDQ), the Family Assessment Device-General
      Functioning scale (FAD-GF), and the Microskin Questionnaire (MQ-a questionnaire
      about their experience using Microskin developed specifically for this study).
      All children were followed up with the same measures 6 months after their
      completed use of Microskin. RESULTS: After the 5-week Microskin trial there was
      improvement on all scales of the SDQ for the 10 children in the first treatment
      group but not for the wait-list group. After the wait-list group used
      Microskinfor 5 weeks they too improved on all scales. Combining the results for
      all 20 children from before to after using Microskin there was a statistically
      significant improvement in the SDQ Emotional Symptoms and Total Difficulties.
      There was also improved perception of family functioning after using Microskin.
      Six-month follow-up data showed continued psychosocial improvement. Overall,
      children felt more confident, happier, and enjoyed social outings more when they
      had Microskin on, with 95% intending to continue to use Microskin. CONCLUSIONS:
      Microskin improves psychosocial functioning in pediatric burn patients and is
      well-tolerated and acceptable. The small sample size precludes sophisticated
      statistical analyses and generalization of results. There is a need for a full
      scale randomized controlled study of Microskin with a larger sample size.

PMID- 18082961
TI  - Core warming of a burn patient during excision to prevent hypothermia.

PMID- 18082962
TI  - Hepatocellular carcinoma in a young survivor of major burns.

PMID- 18082963
TI  - The factor age and the recovery of severely burned children.
AB  - PURPOSE: It is not known if the recovery of pediatric burn patients is age
      dependent. The aim of this study was to investigate the effect of age on the
      recovery of body composition of severely burned children. PROCEDURES: Pediatric
      patients with massive burns, >or= 40% of total body surface area, were followed
      over 2 years. Patients were divided into two age groups: 0-3.9 years old and 4
      17.9 years old at the time of burn. Body composition was determined at hospital
      discharge, 6, 9, 12, 18, and 24 months after burn using dual-X-ray
      absorptiometry. Data analysis was performed using a two way ANOVA followed by
      Tukey's correction when appropriate. Significance was accepted at p<0.05.
      FINDINGS: Twenty-four patients were enrolled (age 0-3.9: n=9; age 4-17.9: n=15).
      Percent changes in height and bone mineral content were significantly increased
      in the younger age group, p<0.05. In contrast, percent changes in lean body mass
      were significantly lower in younger patients, p<0.05. Percent changes in total
      body fat mass were not affected. CONCLUSION: Patterns of recovery in pediatric
      burn patients are determined by age. This observation should be considered in the
      development of therapeutic approaches.

PMID- 18082964
TI  - Phosphatase and tensin homolog, deleted on chromosome 10 deficiency in brain
      causes defects in synaptic structure, transmission and plasticity, and
      myelination abnormalities.
AB  - The phosphatidylinositol 3-kinase (PI3K) signaling pathway modulates growth,
      proliferation and cell survival in diverse tissue types and plays specialized
      roles in the nervous system including influences on neuronal polarity, dendritic
      branching and synaptic plasticity. The tumor-suppressor phosphatase with tensin
      homology (PTEN) is the central negative regulator of the PI3K pathway. Germline
      PTEN mutations result in cancer predisposition, macrocephaly and benign
      hamartomas in many tissues, including Lhermitte-Duclos disease, a cerebellar
      growth disorder. Neurological abnormalities including autism, seizures and ataxia
      have been observed in association with inherited PTEN mutation with variable
      penetrance. It remains unclear how loss of PTEN activity contributes to
      neurological dysfunction. To explore the effects of Pten deficiency on neuronal
      structure and function, we analyzed several ultra-structural features of Pten
      deficient neurons in Pten conditional knockout mice. Using Golgi stain to
      visualize full neuronal morphology, we observed that increased size of nuclei and
      somata in Pten-deficient neurons was accompanied by enlarged caliber of neuronal
      projections and increased dendritic spine density. Electron microscopic
      evaluation revealed enlarged abnormal synaptic structures in the cerebral cortex
      and cerebellum. Severe myelination defects included thickening and unraveling of
      the myelin sheath surrounding hypertrophic axons in the corpus callosum. Defects
      in myelination of axons of normal caliber were observed in the cerebellum,
      suggesting intrinsic abnormalities in Pten-deficient oligodendrocytes. We did not
      observe these abnormalities in wild-type or conditional Pten heterozygous mice.
      Moreover, conditional deletion of Pten drastically weakened synaptic transmission
      and synaptic plasticity at excitatory synapses between CA3 and CA1 pyramidal
      neurons in the hippocampus. These data suggest that Pten is involved in
      mechanisms that control development of neuronal and synaptic structures and
      subsequently synaptic function.

PMID- 18082965
TI  - Synaptic terminals from mice midbrain exhibit functional P2X7 receptor.
AB  - P2X(7) receptor has been recently localized in mice cerebellar granule neuron
      fibers. Here, the expression of this subunit has been detected in wild type mice
      midbrain, by quantitative real time-polymerase chain reaction,
      immunocytochemistry and Western blot assays. The functionality of this P2X(7)
      subunit has been confirmed using microfluorimetric experiments in isolated
      synaptic terminals from mice midbrain. 2'-3'-O-(4-benzoylbenzoyl)-ATP (BzATP) was
      30-fold more potent than ATP and EC(50) values were 20 microM and 630 microM
      respectively. Brilliant Blue G (BBG) and 1-[N,O-bis(5-isoquinolinesulfonyl)-N
      methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) produced an inhibition in the
      responses induced by BzATP, with IC(50) values of 0.027 nM and 2.23 nM,
      respectively. In addition, P2X(7) inhibitors as ZnSO(4), BBG and suramin
      abolished partially or totally the responses induced by the physiological agonist
      ATP. According to immunochemical and PCR assays the presence of a "P2X(7)-like"
      protein in synaptosomes from validated P2X(7) knockout (KO) model have been
      detected. In KO animals, BzATP was sixfold more potent than ATP and the EC(50)
      values were 87 microM and 590 microM respectively. BBG and KN-62 also produced an
      inhibition in the responses induced by BzATP, with IC(50) value of 0.61 nM and
      118 nM respectively, both of them higher than in wild type mice. Moreover, the
      calcium mobilization ability of native P2X(7) receptors was higher in control
      compared with KO mice. These biochemical and pharmacological experiments are
      consistent with the presence of a functional P2X(7) receptor in wild type mice
      midbrain, and the existence of a less efficient "P2X(7)-like" receptor in the KO
      model.

PMID- 18082966
TI  - Bone morphogenetic protein-7 reduces toxicity induced by high doses of
      methamphetamine in rodents.
AB  - Methamphetamine (MA) is a drug of abuse as well as a dopaminergic neurotoxin. We
      have previously demonstrated that pretreatment with bone morphogenetic protein 7
      (BMP7) reduced 6-hydroxydopamine-mediated neurodegeneration in a rodent model of
      Parkinson's disease. In this study, we examined the neuroprotective effects of
      BMP7 against MA-mediated toxicity in dopaminergic neurons. Primary dopaminergic
      neurons, prepared from rat embryonic ventral mesencephalic tissue, were treated
      with MA. High doses of MA decreased tyrosine hydroxylase immunoreactivity (THir)
      while increasing terminal deoxynucleotidyl transferase-mediated dNTP nick end
      labeling. These toxicities were significantly antagonized by BMP7. Interaction of
      BMP7 and MA in vivo was first examined in CD1 mice. High doses of MA (10 mg/kgx4
      s.c.) significantly reduced locomotor activity and THir in striatum. I.c.v.
      administration of BMP7 antagonized these changes. In BMP7 +/- mice, MA suppressed
      locomotor activity and reduced TH immunoreactivity in nigra reticulata to a
      greater degree than in wild type BMP7 +/+ mice, suggesting that deficiency in
      BMP7 expression increases vulnerability to MA insults. Since BMP7 +/- mice also
      carry a LacZ-expressing reporter allele at the BMP7 locus, the expression of BMP7
      was indirectly measured through the enzymatic activity of beta-galactosidase
      (beta-gal) in BMP7 +/- mice. High doses of MA significantly suppressed beta-gal
      activity in striatum, suggesting that MA may inhibit BMP7 expression at the
      terminals of the nigrostriatal pathway. A similar effect was also found in CD1
      mice in that high doses of MA suppressed BMP7 mRNA expression in nigra. In
      conclusion, our data indicate that MA can cause lesioning in the nigrostriatal
      dopaminergic terminals and that BMP7 is protective against MA-mediated
      neurotoxicity in central dopaminergic neurons.

PMID- 18082967
TI  - Frequency tuning and firing pattern properties of auditory thalamic neurons: an
      in vivo intracellular recording from the guinea pig.
AB  - We investigated the firing pattern and frequency tuning properties of medial
      geniculate body (MGB) neurons, through in vivo intracellular recordings in
      anesthetized guinea pigs. Twenty-two of the 25 physiological characterized
      neurons were anatomically identified. Ten neurons were located in the ventral
      division of the medial geniculate body (MGv) (seven in pars ovoidea (OV) and
      three in the pars lateralis (LV)). Eight were located in the dorsal division
      (MGd), and four in the medial division (MGm). OV neurons showed a uniform, phasic
      ON response with high frequency selectivity. Functionally, they are interpreted
      as relaying spectral information with high reliability. LV neurons exhibited
      various patterns: phasic, tonic and excitatory postsynaptic potentials (EPSP)
      with a spike train. These high magnitude EPSPs are proposed to convey temporal
      information of the auditory signals with more encoding power. MGd neurons had
      relatively low best frequencies while MGm neurons had high intensity threshold,
      broader frequency selectivity, and a tonic response pattern. Tonic firing is
      likely to impose a strong impact onto wide cortical area and amygdala. When
      hyperpolarized with current injection, MGB neurons evoked low-threshold calcium
      spikes. Distinct change in these spike numbers was observed among MGv and MGd
      neurons as compared with MGm neurons, implying their differential roles. MGm
      neurons are more modulatory in nature, while the long lasting bursts of low
      threshold calcium spikes observed in MGv and MGd neurons probably participate in
      propagating the sleep oscillations.

PMID- 18082969
TI  - Involvement of endoplasmic reticulum stress in the neuronal death induced by
      transient forebrain ischemia in gerbil.
AB  - Endoplasmic reticulum (ER) stress, which is caused by an accumulation of unfolded
      proteins in the ER lumen, is associated with stroke and with neurodegenerative
      diseases such as Parkinson's and Alzheimer diseases. We assessed the expression
      patterns of immunoglobulin heavy chain binding protein (BiP)/glucose-regulated
      protein (GRP) 78 (an ER-resident molecular chaperone whose expression serves as a
      good marker of ER-stress), activating transcription factor (ATF)-4, and C/EBP
      homology protein (CHOP) by immunohistochemistry and/or Western blotting after
      transient forebrain ischemia in gerbils. Double-fluorescent staining involving
      CHOP immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated
      DNA nick-end labeling (TUNEL) method was performed to clarify the involvement of
      CHOP in cell death. Immunohistochemical and Western blot analyses of the
      hippocampal Cornet d'Ammon (CA)1 subfield showed that BiP expression was
      increased at 12 h, peaked at 3 days, then decreased (versus the control group). A
      transient increase was detected in CA3 at 1 day after ischemia, but BiP
      expression was unchanged in dentate gyrus and cortex. Signals for ATF-4 and CHOP
      were increased at 1 day and 3 days in CA1, and at 12 h in CA3. Co-localization of
      CHOP immunoreactivity and DNA fragmentation was detected by the TUNEL method at 3
      days after ischemia in CA1, but not at 12 h in CA3. These findings are consistent
      with ER stress playing a pivotal role in post-ischemic neuronal death in the
      gerbil hippocampal CA1 subfield.

PMID- 18082968
TI  - Lipopolysaccharide suppresses activation of the tuberomammillary histaminergic
      system concomitant with behavior: a novel target of immune-sensory pathways.
AB  - Infection and inflammation strongly inhibit a variety of behaviors, including
      exploration, social interaction, and food intake. The mechanisms that underlie
      sickness behavior remain elusive, but appear to involve fatigue and a state of
      hypo-arousal. Because histaminergic neurons in the ventral tuberomammillary
      nucleus of the hypothalamus (VTM) play a crucial role in the mediation of
      alertness and behavioral arousal, we investigated whether the histaminergic
      system represents a target for immune activation and, if so, whether modulation
      by ascending medullary immune-sensitive projections represents a possible
      mechanism. Rats were injected intraperitoneally with either the pro-inflammatory
      stimulus lipopolysaccharide (LPS) or saline, and exposed to one of various
      behavioral tests that would induce motivated behavior (exploration, play
      behavior, social interaction, sweetened milk consumption). Upon kill, brains were
      processed for c-Fos and histidine decarboxylase immunoreactivity. LPS treatment
      reduced behavioral activity and blocked behavioral test-associated c-Fos
      induction in histaminergic neurons of the VTM. These effects of LPS were
      prevented by prior inactivation of the caudal medullary dorsal vagal complex
      (DVC) with a local anesthetic. To determine whether LPS-responsive brainstem
      projection neurons might provide a link from the DVC to the VTM, the tracer
      Fluorogold was iontophoresed into the VTM a week prior to experiment.
      Retrogradely labeled neurons that expressed c-Fos in response to LPS treatment
      included catecholaminergic neurons within the nucleus of the solitary tract and
      ventrolateral medulla. These findings support the hypothesis that the
      histaminergic system represents an important component in the neurocircuitry
      relevant for sickness behavior that is linked to ascending pathways originating
      in the lower brainstem.

PMID- 18082970
TI  - Courtship pheromone-induced c-Fos-like immunolabeling in the female salamander
      brain.
AB  - Plethodontid salamanders display intricate courtship behaviors. Proteinaceous
      courtship pheromones were recently discovered in the submandibular (mental) gland
      of the male Plethodon shermani, the red-legged salamander. Behavioral studies
      showed that these male pheromones are delivered by direct contact to the female
      snout and modulate her receptivity during courtship. Previous reports
      demonstrated that experimental application of courtship pheromones activates
      vomeronasal sensory neurons in P. shermani. The present study investigated the
      CNS response to courtship pheromones in that species using immunocytochemical
      detection of the immediate-early gene product c-Fos. The results show that
      application of a male gland extract to females activated Fos-like immunolabeling
      in the extended vomeronasal amygdala of the accessory olfactory system, as well
      as in the preoptic area and ventromedial hypothalamus; regions of the brain known
      to mediate reproductive responses in vertebrates. The gland extract additionally
      activated Fos-like labeling in the raphe median, possibly indicating a
      serotonergic activation. Application of individual purified courtship pheromone
      proteins resulted in increases in Fos-like labeling in some of the regions
      activated by the complete submandibular gland extract, but the pattern of
      labeling was not as clear as that of the complete extract. Unlike other known
      vertebrate reproductive pheromones, courtship pheromones in P. shermani were
      effective only at a high concentration. This could result from the particular
      mode of pheromone transfer in that species, which involves sustained direct
      contact between male and female. It is concluded that salamander courtship
      pheromones exert their influence on behavior through the vomeronasal pathway and
      its direct projections to the preoptic and hypothalamic regions.

PMID- 18082971
TI  - Activity-dependent secretion of neuronal activity regulated pentraxin from
      vasopressin neurons into the systemic circulation.
AB  - Neuronal activity regulated pentraxin (Narp) is a secreted, synaptic protein that
      has been implicated in modulating synaptic transmission. However, it is unclear
      how Narp secretion is regulated. Since we noted prominent Narp immunostaining in
      vasopressin neurons of the hypothalamus and in the posterior pituitary, we
      assessed whether it, like vasopressin, is released into the systemic circulation
      in an activity-dependent fashion. Consistent with this hypothesis, electron
      microscopic studies of the posterior pituitary demonstrated that Narp is located
      in secretory vesicles containing vasopressin. Using affinity chromatography, we
      detected Narp in plasma and found that these levels are markedly decreased by
      hypophysectomy. In addition, we confirmed that injection of a viral Narp
      construct into the hypothalamus restores plasma Narp levels in Narp knockout
      mice. In checking for activity-dependent secretion of Narp from the posterior
      pituitary, we found that several stimuli known to trigger vasopressin release,
      i.e. hypovolemia, dehydration and endotoxin, elevate plasma Narp levels. Taken
      together, these findings provide compelling evidence that Narp is secreted from
      vasopressin neurons in an activity-dependent fashion.

PMID- 18082972
TI  - Identification and characterization of a subset of mouse sensory neurons that
      express acid-sensing ion channel 3.
AB  - Acid-sensing ion channel 3 (ASIC3) is the most sensitive acid sensor in sensory
      neurons that innervate into skin, muscle, heart, and visceral tissues. ASIC3 is
      involved in ischemia sensing, nociception, mechanosensation, and hearing, but how
      ASIC3-expressing neurons differ in their firing properties is still unknown. We
      hypothesized that ASIC3-expressing neurons have specialized firing properties,
      which, coupled with the heterogeneity of acid-sensing properties, accounts for
      various physiological roles. Here, we successfully identified ASIC3-expressing
      lumbar dorsal root ganglion (DRG) neurons whose transient proton-gated currents
      were blocked by salicylic acid (SA). The salicylic acid-sensitive (SAS) neurons
      did not exist in DRG neurons of mice lacking ASIC3. SAS neurons expressed
      distinct electrophysiological properties as compared with other DRG neurons.
      Especially, SAS neurons fired action potentials (APs) with large overshoot and
      long afterhyperpolarization duration, which suggests that they belong to
      nociceptors. SAS neurons also exhibited multiple nociceptor markers such as
      capsaicin response (38%), action potential (AP) with inflection (35%), or
      tetrodotoxin resistance (31%). Only in SAS neurons but not other DRG neurons was
      afterhyperpolarization duration correlated with resting membrane potential and AP
      duration. Our studies reveal a unique feature of ASIC3-expressing DRG neurons and
      a basis for their heterogeneous functions.

PMID- 18082973
TI  - Acute induction of epileptiform discharges by pilocarpine in the in vitro
      isolated guinea-pig brain requires enhancement of blood-brain barrier
      permeability.
AB  - Systemic application of the muscarinic agonist, pilocarpine, is commonly utilized
      to induce an acute status epilepticus that evolves into a chronic epileptic
      condition characterized by spontaneous seizures. Recent findings suggest that the
      status epilepticus induced by pilocarpine may be triggered by changes in the
      blood-brain barrier (BBB) permeability. We tested the role of the BBB in an acute
      pilocarpine model by using the in vitro model brain preparation and compared our
      finding with in vivo data. Arterial perfusion of the in vitro isolated guinea-pig
      brain with <1 mM pilocarpine did not cause epileptiform activity, but rather
      reduced synaptic transmission and induced steady fast (20-25 Hz) oscillatory
      activity in limbic cortices. These effects were reversibly blocked by co
      perfusion of the muscarinic antagonist atropine sulfate (5 microM). Brain
      pilocarpine measurements in vivo and in vitro suggested modest BBB penetration.
      Pilocarpine induced epileptiform discharges only when perfused with compounds
      that enhance BBB permeability, such as bradykinin (n=2) or histamine (n=10). This
      pro-epileptic effect was abolished when the BBB-impermeable muscarinic antagonist
      atropine methyl bromide (5 microM) was co-perfused with histamine and
      pilocarpine. In the absence of BBB permeability enhancing drugs, pilocarpine
      induced epileptiform activity only after arterial perfusion at concentrations >10
      mM. Ictal discharges correlated with a high intracerebral pilocarpine
      concentration measured by high pressure liquid chromatography. We propose that
      acute epileptiform discharges induced by pilocarpine treatment in the in vitro
      isolated brain preparation are mediated by a dose-dependent, atropine-sensitive
      muscarinic effect promoted by an increase in BBB permeability. Pilocarpine
      accumulation secondary to BBB permeability changes may contribute to in vivo
      ictogenesis in the pilocarpine epilepsy model.

PMID- 18082974
TI  - A comparison of the physiological, behavioral, neurochemical and microglial
      effects of methamphetamine and 3,4-methylenedioxymethamphetamine in the mouse.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) are
      amphetamine analogues with similar persistent neurochemical effects in the mouse
      which some have described as neurotoxicity. We attempted to identify dose
      regimens of MDMA and METH with similar effects on behavioral and physiological
      variables in the mouse, then quantified the effects of these dose regimens on
      neurochemistry and microglial markers. Four discrete injections of saline, MDMA
      (10, 20, or 30 mg/kg), or METH (5 or 10 mg/kg) were administered to mice at 2 h
      intervals. Body weight was quantified immediately before each injection, and 2 h
      after the last injection, while core temperature and locomotor activity were
      continuously monitored via radiotelemetry. Mice were killed 72 h after the final
      injection and brains were rapidly dissected on ice. Dopamine content in various
      brain regions was quantified via high pressure liquid chromatography (HPLC), and
      microglial activation was assessed by saturation binding of the peripheral
      benzodiazepine receptor (PBR) ligand 1-(2-chlorophenyl)-N-methyl-N-(1
      methylpropyl)-3-isoquinoline carboxamide ([(3)H]PK11195). Specific dose regimens
      of MDMA and METH induced similar reductions in body weight, depletions of
      dopamine and its metabolites, and similar hyperthermic and locomotor stimulant
      effects, but only METH activated microglia in striatum. These results suggest
      that repeated high doses of MDMA and METH that produce hyperthermia, locomotor
      stereotypy, weight loss and neurochemical depletion are not consistently
      accompanied by microglial activation. The finding that METH, but not MDMA,
      induces microglial effects in the striatum consistent with neurotoxicity might
      imply different mechanisms of toxic action for these two psychostimulants.

PMID- 18082976
TI  - [Risk of breast cancer related to pregnancy].
AB  - After a pregnancy, there is a transitory increase in the risk of breast cancer.
      During the pregnancy, the number of mammary epithelial cells increases massively.
      This increase seems partly due to the expansion of stem cells and proliferating
      intermediate cells. This proliferation of epithelial cells is accompanied by
      angiogenesis and by recruitment of stromal cells, as well as changes of the
      extracellular matrix. During any pregnancy, there is cell trafficking between
      mother and foetus. Hematopoietic or mesenchymal foetal stem cells are transferred
      in maternal circulation and could be used by the tumor as support cells and take
      part in the tumoral development. The study of the mechanisms of this specific
      oncogenesis may help to develop chemoprevention strategies.

PMID- 18082975
TI  - Whites have a more robust hypothalamic-pituitary-adrenal axis response to a
      psychological stressor than blacks.
AB  - OBJECTIVE: Differences in the hypothalamic-pituitary-adrenal (HPA) axis response
      to stress may confer differences in susceptibility to a variety of diseases. We
      hypothesized that whites would differ from blacks in HPA axis response to a
      psychological stressor. DESIGN: Healthy subjects aged 18-30 were recruited from
      Baltimore, Maryland. At initial assessment, they completed psychometric tests
      measuring anxiety, mood, and personality. Subjects then participated in the Trier
      Social Stress Test (TSST), which consisted of 10 min of public speaking and
      mental arithmetic exercises. Subjective anxiety was measured immediately pre- and
      post-TSST. Race effects on cortisol, adrenocorticotrophin (ACTH), and prolactin
      responses to the TSST were analyzed by GEE longitudinal analysis methods. The
      analysis controlled for gender, baseline hormone levels, socioeconomic factors,
      anxiety, mood, and dimensions of personality. RESULTS: Ninety-eight subjects
      participated in the TSST. Whites had 36% greater relative mean cortisol response
      than blacks (95% CI: 10-67%, P=0.004). Whites had significantly higher mean ACTH
      compared to blacks at 25 min after the start of the TSST (35%, 95% CI: 16-58%
      greater, P<0.001). There was no difference in prolactin response. Of note, whites
      and blacks did not differ in subjective anxiety response to the TSST.
      CONCLUSIONS: In sum, we found that whites have a more robust HPA axis response to
      the TSST compared with blacks, even after controlling for several socioeconomic
      and psychological factors. In contrast, we observed no difference in prolactin
      response. There were no differences in subjective response to the TSST to explain
      the difference in HPA axis response. Further study is indicated to explain this
      finding and to test whether it can be extrapolated to other forms of stress.

PMID- 18082977
TI  - [Liver hernia. Prognosis and report of 11 cases].
AB  - OBJECTIVES: Exclusive hepatocele is defined as a hernia containing in majority
      the liver with possibly some intestinal loops. This study was undertaken to
      evaluate neonatal morbidity and mortality in this series of exclusive
      hepatoceles. MATERIALS AND METHODS: We reviewed 11 cases of exclusive hepatoceles
      with delivery at the hospital Jeanne-de-Flandre in the CHRU of Lille, in France.
      RESULTS: The mean gestational age of diagnosis was 14.5+/-3.4 weeks of gestation.
      Karyotype determination was performed in 100% of cases: it was abnormal in one
      case of 11. One termination of pregnancy was performed because of trisomy 13. The
      mean gestational age at delivery was 38+/-1.8 weeks of gestation. Cesarean
      deliveries were performed in nine cases. Morbidity was important with: one case
      of fetal growth retardation on total hepatocele, three cases of severe
      respiratory distress, two cases of severe digestive complications. The mean
      length of stay was 42.8 days. The mean length of parenteral feeding was 14.4
      days. Postnatal mortality concerned one child, which died because of a severe
      respiratory distress due to pulmonary hypoplasia. CONCLUSION: In this series,
      morbidity is thus important, making of exclusive hepatoceles a full entity among
      the omphaloceles. The multidisciplinary take care is more complex but
      conceivable.

PMID- 18082978
TI  - Elucidation of the DNA sequence of Streptococcus uberis adhesion molecule gene
      (sua) and detection of sua in strains of Streptococcus uberis isolated from
      geographically diverse locations.
AB  - Streptococcus uberis is an important environmental pathogen that causes
      subclinical and clinical mastitis in lactating and nonlactating cows throughout
      the world. S. uberis adhesion molecule (SUAM) was identified recently by our
      laboratory and we hypothesize that SUAM is a potential virulence factor involved
      in the pathogenesis of S. uberis mastitis. The first objective of the present
      study was to clone and sequence the SUAM gene (sua) from S. uberis UT888. The
      second objective was to determine the prevalence of sua in strains of S. uberis
      isolated from geographically diverse locations. The 20 amino acid N-terminal
      sequence of purified SUAM was utilized to identify a single open reading frame
      (ORF) in the S. uberis O140J (ATCC BAA-854) genome database. Three sets of
      primers were identified from this sequence for amplification of sub-fragments and
      the complete gene encoding SUAM. Restriction fragment analysis of the largest
      polymerase chain reaction (PCR) product confirmed the desired fragment had been
      amplified. This 2970bp PCR fragment was cloned into plasmid pCR-XL-TOPO and
      sequenced. The S. uberis UT888 sua sequence (NCBI Accession no. DQ232760) was 99%
      similar to the S. uberis O140J database sequence. The three pairs of PCR primers
      were used in a subsequent experiment to identify sua in 12 strains of S. uberis
      isolated in milk from dairy cows with mastitis in Tennessee (n=6), Colorado
      (n=1), Washington (n=1), New Zealand (n=1) and from the American Type Culture
      Collection (n=3). Primer pairs yielded the expected 2970, 2639 and 2362bp PCR
      fragments in all strains evaluated. In conclusion, we cloned and sequenced sua,
      which codes for the first described S. uberis adhesin, SUAM. sua was detected in
      all strains of S. uberis evaluated suggesting that it is conserved.

PMID- 18082979
TI  - Studies on liquefaction and storage of ejaculated dromedary camel (Camelus
      dromedarius) semen.
AB  - The purpose of this study was to evaluate seminal liquefaction and quality of
      ejaculated camel semen during storage in different extenders at room (23 degrees
      C) and refrigeration (4 degrees C) temperature. Semen was collected using an
      artificial vagina and diluted immediately (1:1), using a split-sample technique,
      in five extenders [(1) Tris-tes egg yolk, (2) Tris-lactose egg yolk, (3) citrate
      egg yolk, (4) sucrose egg yolk and (5) Tris-fructose egg yolk], while one
      fraction was kept without an extender to act as control. The semen was
      transported to the lab at 37 degrees C, in a portable incubator within half an
      hour, and thereafter liquefaction of semen was monitored every 15 min. After
      complete liquefaction of the semen it was evaluated for sperm concentration and
      morphology and then was extended to a final ratio of 1:3. Aliquots of each semen
      sample were then stored at refrigeration and room temperature. The average volume
      of an ejaculate was 4.3+/-0.4 mL and it had a very viscous consistency. The
      average concentration of spermatozoa was 230.4+/-10.7 x 10(6)mL(-1) and the
      proportion of spermatozoa with protoplasmic droplets averaged 1.02+/-0.2, while
      2.7+/-0.6 and 9.7+/-2.9% had mid-piece and tail abnormalities, respectively. All
      extended semen samples liquefied within 1.5h at 37 degrees C, however, there was
      slow liquefaction in the sample without an added extender (control). Best
      liquefaction was observed in Tris-lactose extender followed by Tris-fructose and
      citrate egg yolk diluents whereas in the other two extenders there was head-to
      head agglutination of the spermatozoa. There was no difference in the initial
      motility of the spermatozoa in extenders 1-5 after its liquefaction, however,
      after 24 and 48 h of storage a higher proportion of spermatozoa were motile in
      extenders 1, 2 and 4 (P<0.05) at both the temperatures. There was a gradual
      decline in viability of the spermatozoa in all extenders at both the
      temperatures, although, a high portion of the spermatozoa had intact acrosomes
      throughout the storage period. It may be concluded that dromedary semen, when
      added to an extender (1:1) immediately after collection, liquefies within 60-90
      min at 37 degrees C. It maintains a high proportion of motile and viable
      spermatozoa that can survive storage up to 48 h in Tris-lactose egg yolk, Tris
      tes egg yolk and sucrose egg yolk diluents. However, best liquefaction and
      progressive sperm motility is achieved in Tris-lactose egg yolk extender.

PMID- 18082980
TI  - Dog model with implanted pump to test boosters for antiretroviral medication.
AB  - A dog model was developed to test the capacity of boosters for antiretroviral
      medication. Two dogs were implanted with a modified constant-flow Codman 3000
      infusion pump, adapted to release viscous solutions of darunavir (TMC114) at a
      constant rate of 25mg/dog/day in the venous blood stream. Booster candidates were
      given by oral gavage for at least 4 days up to maximum 7 days in cross-over
      fashion, separated by a wash-out period of minimum 1 week. The booster candidates
      were tested at doses of 20 and/or 40mg/kg/day: blood sampling for determination
      of the boosting effect was performed on the last day of booster administration.
      The model allowed to (1) compare the boosting ratio of these booster candidates
      based on the exposure (determination of the area under the curve (AUC) of
      darunavir in presence versus absence of the booster candidate), (2) detect delay
      in boosting activity by evaluation of the shift of Cmax of darunavir following
      booster administration versus the Cmax of the booster candidate) and (3)
      calculate the intrinsic booster capacity, by correcting for the systemic exposure
      of booster candidate by normalizing the booster ratio for the booster's AUC. The
      latter parameter (intrinsic booster capacity) allows to determine the booster's
      metabolic contribution in inhibiting the metabolism of antiretroviral medication
      (most likely via inhibition of CYP3A4), minimizing the impact of potential
      effects of the booster at the level of the gastro-intestinal tract.

PMID- 18082981
TI  - Inhibitory effect of docosahexaenoic acid (DHA) on the intestinal metabolism of
      midazolam: in vitro and in vivo studies in rats.
AB  - The aim of this study was to evaluate the effects of docosahexaenoic acid (DHA)
      on the intestinal cytochrome P450 isoenzyme (CYP3A) and P-glycoprotein (P-gp)
      functions using midazolam and rhodamine-123 as specific substrates of CYP3A and P
      gp, respectively. Perfused everted intestinal segments from rats were employed to
      determine the effects of DHA on midazolam metabolism and rhodamine-123 transport.
      In addition, the effects of DHA on in vitro midazolam metabolism in rat
      intestinal microsomes and on midazolam bioavailability in rats were examined. The
      intestinal extraction ratio (ER G) of midazolam was determined to be 0.43 and
      decreased significantly to 0.12, 0.07, and 0.06 in the presence of 50, 100, and
      200 microM DHA, respectively, in a concentration-dependent manner. The results
      from an in vitro study using rat intestinal microsomes demonstrated that DHA
      competitively inhibited the intestinal CYP3A activity with Ki of 15.7 and 27.1
      microM for the formations of 1'-OH midazolam and 4-OH midazolam, respectively.
      Moreover, the oral administration of DHA (100mg/kg) increased the AUC infinity,
      Cmax, and oral bioavailability (F) of midazolam by about 50% in rats, without
      affecting the T 1/2, V dss/F, or CL tot/F. In contrast, DHA did not change the
      serosal-to-mucosal transport of rhodamine-123 in the perfused everted intestine
      and oral administration of DHA (100mg/kg) had no influence on the
      pharmacokinetics of intravenously administered midazolam in rats, thus suggesting
      that DHA has little effect on the intestinal P-gp activity and hepatic clearance
      of midazolam. This study provided the first direct evidence to show that DHA has
      an inhibitory effect on the intestinal pre-systemic metabolism of a CYP3A
      substrate and that DHA has little, if any, effect on the P-gp activity in the
      gut.

PMID- 18082982
TI  - In vitro release and stability of an artesunate rectal gel suitable for pediatric
      use.
AB  - The rectal route is indicated to treat patients with rapidly evolving malaria who
      cannot take oral medication to prevent progression to severe forms of the
      disease. Improvement can be made in terms of rectal bioavailability and stability
      of current formulations. We studied a new two-compartment, muco-adhesive gel
      formulation of artesunate which is adapted for use in children and storage in
      tropical climates. The formulation contains 50mg of artesunate per gram of gel.
      Because of its instability in aqueous solutions, artesunate is in the dry
      component of the gel with Carbopol and separate from the liquid phase until
      reconstitution. Artesunate is stable in the dry blend for 6 months at 45 degrees
      C and 60% RH. The gel should be used between 1 and 72 h after being
      reconstituted. Artesunate release was measured by with a rapid, simple and
      reliable HPLC-UV which allowed the analysis of artesunate and dihydroartemisinin
      with an analysis time at 3 min. The amount of artesunate released over 6h was 56
      +/- 0.97%. Compared to the reference suspension, total release and dissolution
      efficiency were lower and rate of release was slower (time to 50% dissolution 271
      +/- 21 min), probably because of the higher viscosity of the gel, but the drug
      release profiles were similar. The calculated in vitro release exponent (n) value
      suggested that artesunate is released from the gel by non-Fickian transport.

PMID- 18082983
TI  - Binaural perception of the modulation depth of AM signals.
AB  - The purpose of this study was to determine the binaurally perceived modulation
      depth (m) of the low rate amplitude modulated (AM) signals, under conditions of
      their dichotic presentation, i.e., when the AM signals presented to the left and
      the right ear had different modulation depths. The modulation depth was
      determined as a point of subjective equality between the sensations of the
      modulation depth of AM signals presented to the left and right ear, using a one
      up, one-down adaptive procedure. Measurements were made for the carrier
      frequencies (f(c)) of 250, 1000, and 4000Hz, and the modulation frequency (f(m))
      of 4Hz. Experimental data showed that, for sufficiently small interaural
      difference in modulation depth (Deltam), the perceived modulation approximated
      the mean of the modulation depths presented to the left and the right ear.
      However, for moderate and large Deltam, the binaurally perceived modulation was
      lower than the mean of m(l) and m(r) and the steepness of the function
      m=f(Deltam) gradually decreased with an increase of Deltam. Results of the
      calculation of the binaurally perceived modulation depth, obtained on the
      assumption of binaural loudness summation, were found to be consistent within the
      limit of standard deviation, with the experimental data for relatively wide range
      of Deltam.

PMID- 18082984
TI  - The impact of mitochondrial energetic dysfunction on apoptosis in outer hair
      cells of the cochlea following exposure to intense noise.
AB  - Previous studies have shown that exposure to intense noise causes outer hair
      cells (OHCs) to die, primarily through the process of apoptotic degeneration. The
      current study was designed to examine the regulatory role of mitochondrial
      bioenergetic function in controlling the initiation and execution of the
      apoptotic process of OHCs. Chinchilla cochleae were treated with 3-nitropropionic
      acid (3-NP, 20 or 50mM), an irreversible inhibitor of succinate dehydrogenase
      (SDH), to inhibit the mitochondrial energy production before and after exposure
      to 75 pairs of impulses at 155dB pSPL. Comparison of the noise-exposed cochleae
      treated with and without 3-NP revealed that the inhibition of SDH activity
      delayed nuclear degradation in apoptotic OHCs. However, the initiation of
      apoptosis appeared to be undeterred. There was no major shift of cell death
      pathways from apoptosis to necrosis, although a small portion of OHCs showed
      signs of secondary necrosis. Collectively, the results of the study suggest that,
      while the mitochondrial energetic function plays an important role in regulating
      the apoptotic process, its dysfunction has a limited influence on the suppression
      of apoptotic induction in OHCs following exposure to intense noise.

PMID- 18082986
TI  - Nizatidine enhances salivary secretion in patients with dry mouth.
AB  - OBJECTIVE: It was reported that salivary secretion increased in 30 volunteers
      with administered nizatidine. The aim of the present study was to investigate
      whether or not nizatidine enhances salivary secretion and improves the function
      of salivary glands in patients with dry mouth. METHODS: Both basal and stimulated
      salivary secretions were measured before and after the administration of
      nizatidine for a month in 18 healthy adult volunteers and 38 patients with dry
      mouth. In 6/38 patients, salivary gland scintigraphy was performed. RESULTS:
      After the administration of nizatidine for a month, salivary secretions
      significantly increased in the control and dry mouth patient groups compared to
      the pretreatment baseline. In addition, 25 of 38 dry mouth patients showed
      subjective improvements of oral dryness. In 3/4 patients, the function of
      salivary glands was improved on salivary gland scintigraphy. CONCLUSION:
      Nizatidine may reactivate salivary gland cells and be useful in the treatment of
      patients with dry month.

PMID- 18082985
TI  - A systemic gentamicin pathway across the stria vascularis.
AB  - The mechanism(s) by which systemically-administered aminoglycosides enter the
      cochlea remain poorly understood. To elucidate which mechanisms may be involved,
      we co-administered different molar ratios of gentamicin and fluorescent
      gentamicin (GTTR) to mice in three different regimens: (1) gentamicin (150, 300
      or 600mg/kg) containing a constant 300:1 molar ratio of gentamicin:GTTR; (2)
      300mg/kg gentamicin containing a variable molar ratio of gentamicin:GTTR (150:1
      600:1), or (3) an increasing dose of gentamicin (150-900mg/kg), each dose
      containing 1.7mg/kg GTTR. Three hours later, cochleae were fixed and examined by
      confocal microscopy. First, increasing doses of a constant molar ratio of
      gentamicin:GTTR, resulted in increasing intensities of GTTR fluorescence in hair
      cells and strial tissues. Second, a fixed gentamicin dose with increasing molar
      dilution of GTTR led to decreasing GTTR fluorescence in hair cells and strial
      tissues. Third, a fixed GTTR dose with increasing molar dilution by gentamicin
      led to decreased GTTR uptake in hair cells and marginal cells, but not intra
      strial tissues and capillaries. Thus, only hair cell and marginal cell uptake of
      GTTR is competitively inhibited by gentamicin, suggesting that a regulatable
      barrier for gentamicin entry into endolymph exists at the interface between
      marginal cells, the intra-strial space and intermediate cells.

PMID- 18082987
TI  - Developmental dysgraphia with profound hearing impairment: intervention by
      auditory methods enabled by cochlear implant.
AB  - Learning disability combined with hearing impairment (LDHI) is a poor prognostic
      factor for the language development of hearing impaired children after
      educational intervention. A typical example of a child with LDHI and effective
      interventions provided by cochlear implants are presented in this report. A case
      of congenital cytomegaloviral infection that showed dysgraphia as well as
      profound deafness was reported and an underlying visual processing problem
      diagnosed in the present case caused the patient's dysgraphia. The dysgraphia
      could be circumvented by the use of auditory memory fairly established by a
      cochlear implant.

PMID- 18082988
TI  - Polish Centenarians Programme. Multidisciplinary studies of successful ageing:
      aims, methods, and preliminary results.
AB  - Studies of centenarians as a model of successful ageing may help identify various
      environmental, social, psychological, and genetic factors supporting longevity.
      The scientific aims of the programme were to assess health status and
      environmental determinants of ageing of Polish centenarians, and to collect
      biological material for studying selected aspects of longevity, including genetic
      factors. The social aim of the project was to bring public attention to ageing of
      the population, as well as living conditions of elderly individuals. The
      intention of the authors of this paper is to present aims, scope, methods and
      preliminary results of the Polish Centenarians Programme, as well as to provide
      potential new partners for studying various aspects of longevity and ageing with
      the information about available materials collected during the programme. In this
      study, 346 subjects aged 100+ were visited, biological material was collected
      from 285 subjects, and 153 lymphocyte cell lines were immortalized.

PMID- 18082989
TI  - Comprehensive imaging of tumor recurrence in breast cancer patients using whole
      body MRI at 1.5 and 3 T compared to FDG-PET-CT.
AB  - PURPOSE: To compare the diagnostic accuracy for the detection of tumor recurrence
      in breast cancer patients using whole-body-MRI (WB-MRI) at 1.5 or 3T compared to
      FDG-PET-CT. MATERIALS AND METHODS: Thirty-three female patients with breast
      cancer and suspicion of recurrence underwent FDG-PET-CT and WB-MRI. Coronal T1w
      TSE- and STIR-sequences, HASTE-imaging of the lungs, contrast-enhanced T1w- and
      T2w-TSE-sequences of the liver, brain and abdomen were performed, using a WB-MRI
      scanner at 1.5 (n=23) or 3T (n=10). Presence of local recurrence, lymph node
      involvement and distant metastatic disease was assessed using clinical and
      radiological follow-up as a standard of reference. RESULTS: Tumor recurrence was
      found in 20 of 33 patients. Overall 186 malignant foci were detected with WB-MRI
      and PET-CT. Both modalities revealed two recurrent tumors of the breast. PET-CT
      detected more lymph node metastases (n=21) than WB-MRI (n=16). WB-MRI was more
      precise in the detection of distant metastases (n=154 versus n=147). Sensitivity
      was 93% (172/186) and 91% (170/186) for WB-MRI and PET-CT, specificity was 86%
      (66/77) and 90% (69/77), respectively. Examination times for WB-MRI at 1.5 and 3T
      were 51 and 43 min, respectively, examination time for PET-CT was 103 min.
      CONCLUSION: WB-MRI and PET-CT are useful for the detection of tumor recurrence in
      the follow-up of breast cancer. WB-MRI is highly sensitive to distant metastatic
      disease. PET-CT is more sensitive in detecting lymph node involvement. Tumor
      screening with WB-MRI is feasible at 1.5 and 3T, scan time is further reduced at
      3T with identical resolution.

PMID- 18082990
TI  - Computed tomography, magnetic resonance imaging and 11C-metomidate positron
      emission tomography for evaluation of adrenal incidentalomas.
AB  - BACKGROUND: Given the higher sensitivity of modern computed tomography (CT)
      scanners, adrenal incidentalomas are being discovered increasingly often. This
      implies a growing quantitative diagnostic and clinical problem. CT and/or
      magnetic resonance imaging (MRI) and usually thorough hormonal testing are
      routinely used to determine the origin of these lesions. Recently, positron
      emission tomography (PET) using the tracer (11)C-metomidate (MTO) has been
      established as an alternative diagnostic method with high sensitivity for
      identifying adrenocortical lesions. The aim of this study was to evaluate the
      clinical use and value of MTO-PET compared to CT and MRI in the characterisation
      and work-up of adrenal incidentalomas. METHODS: Initially, we retrospectively
      evaluated 20 adrenal incidentalomas in patients who had undergone CT, MRI and MTO
      PET and from whom we had either histopathological diagnosis or clinical follow-up
      data. After this analysis we conducted a prospective study in order to compare
      the imaging modalities. In the latter study, 24 incidentalomas were imaged by CT,
      MRI and MTO-PET and the results were correlated to those from histopathology
      (n=8) and clinical diagnosis after follow-up (n=16). RESULTS: In the
      retrospective analysis, MRI and especially MTO-PET, correlated well to
      histopathology and clinical diagnosis after follow-up, whereas specificity with
      CT was low. This was possibly due to the presence of several haematomas/fibrosis
      which were misdiagnosed as adrenocortical adenomas. In the prospective cohort,
      sensitivity and specificity with CT were 0.71 and 1.0, respectively, and further
      characterisation by MRI increased these values to 0.86 and 1.0, whereas maximum
      sensitivity and specificity were reached when MTO-PET was added. CONCLUSION: The
      diagnosis of an adrenocortical adenoma may be established by CT in most patients
      and by MRI in an additional number. For the few remaining patients needing
      further characterisation, MTO-PET is advantageous as an additional imaging
      modality.

PMID- 18082991
TI  - Decimative subspace-based parameter estimation methods of magnetic resonance
      spectroscopy based on prior knowledge.
AB  - The method Hankel Total Least Squares (HTLS)-PK, which successfully incorporates
      prior knowledge of known signal poles into the method HTLS, has been proven to
      greatly improve the performance for parameter estimation of overlapping peaks of
      magnetic resonance spectroscopy (MRS) signal. In addition, decimation is also
      proposed as a way to increase the performance of subspace-based parameter
      estimation methods in the case of oversampling. Taking advantage of decimation in
      combination with prior knowledge to estimate the MRS signal parameters, two novel
      subspace-based parameter estimation methods, HTLSDSumPK and HTLSDStackPK, are
      presented in this paper. The experimental results and relevant analysis show that
      the methods HTLSDSumPK, HTLSDStackPK and HTLS-PK are slightly better than the
      method HTLS at low noise levels; however, the three prior-knowledge-incorporating
      methods, especially the method HTLSDSumPK, have much better performance than the
      method HTLS at high noise levels in the terms of robustness, estimated accuracy
      and computational complexity. Even if some inaccuracy of prior knowledge is
      considered, the method HTLSDSumPK also shows some advantages.

PMID- 18082992
TI  - Drug safety, drug quality, drug analysis.
AB  - Controlling and minimizing the side effects of drugs are the key issues in
      assuring the safety of drug therapy. Since side effects are inherent properties
      of the drug material, these cannot be influenced by drug analysts. At the same
      time drug analysts play a predominant role in assuring the quality of bulk drug
      materials and drug formulations and this is also closely related to the safety
      issue. The three main attributes of drug quality are identity, strength and
      purity. Of these, in the case of bulk drug materials, purity is of prominent
      importance: by the identification (structure elucidation) and quantitative
      determination of the impurities and degradation products, the risk of their
      contribution to the side effect profile of the drug materials can be avoided or
      at least controlled/minimized. The development in the field of chromatographic
      and spectroscopic methods in the last decades has led to changes in the
      philosophy, structure and requirements in the monographs of drug materials in the
      principal pharmacopoeias. Although the approaches of the European and US
      Pharmacopoeias are somewhat different, a common feature is the shift of focal
      point toward purity tests. In contrast to this, relatively few changes are
      observable in the field of the assay methods for bulk drug materials: non
      selective titrimetric and spectrophotometric methods are still widely used. Since
      the results of these do not contribute to the safety issue, the omission of these
      tests and substitution by the "mass balance" concept is recommended. The
      effectiveness of the tendency of replacing non-selective methods by selective
      ones (mainly HPLC) is also questionable. The reason for this is that due to the
      limited precision of the HPLC assay the drug content obtained by the mass balance
      concept is a much better quality control attribute for bulk drug materials than
      that obtained by HPLC. It is recommended that classical assay methods (including
      HPLC) be used in exceptional cases only and the time and energy thus spared be
      used for more important impurity-related issues that directly contribute to the
      safety of drug therapy.

PMID- 18082993
TI  - Systematic screening and characterization of flavonoid glycosides in Carthamus
      tinctorius L. by liquid chromatography/UV diode-array detection/electrospray
      ionization tandem mass spectrometry.
AB  - The traditional Chinese medicine (TCM) is a complex system, which always consists
      of numerous compounds with significant difference in the content and physical and
      chemical properties. In this paper, a screening method based on target molecular
      weights was developed to characterize the flavonoid glycosides in the flower of
      Carthamus tinctorius L. The screening tables of aglycone and glycan were
      designed, respectively, in order to select and combine freely. The multiple
      reaction monitoring (MRM) scan mode with higher sensitivity and selectivity was
      adopted in the screening, which benefit the characterization for the minor
      components. Seventy-seven flavonoid glycosides were screened out finally, and
      their structures were characterized by tandem mass spectrometric method in both
      positive and negative ion modes. The glycosylation mode, aglycone, sequence
      and/or the interglycosidic linkages of the glycan portion and glycosylation
      position were elucidated by the fragmentation rule in the MS. Numerous compounds
      screened out with this method showed the structure variety in secondary plant
      metabolites, and the purposeful screening systemically and subsequent structure
      characterization offered more information about the chemical constitutions of
      TCM.

PMID- 18082994
TI  - Emerging toxin A-B+ variant strain of Clostridium difficile responsible for
      pseudomembranous colitis at a tertiary care hospital in Korea.
AB  - Sixty percent to 80% of Clostridium difficile isolates in Korea have been
      reported to be toxigenic. However, over 1 year, we encountered a high number of
      tcdA-tcB+ strains associated with pseudomembranous colitis (PMC). C. difficile
      was isolated from 224 of 471 specimens (47.6%) from 371 patients. A subset of the
      culture-positive specimens (n = 106), containing no duplicate cases, was randomly
      selected for tcdA and tcdB polymerase chain reaction (PCR) assays. PCR results
      showed that tcdA+tcdB+ and tcdA-tcdB+ strains accounted for 39.6% (42/106) and
      50.9% (54/106), respectively. Endoscopy, performed on 55/106 patients, revealed
      29 with PMC, 5 with colitis, 14 with other colon diseases, and 7 normal cases.
      Among the 29 PMC cases, 21 (72.4%) were associated with tcdA-tcdB+ strains (P =
      0.0016). These results revealed the possible emergence of tcdA-tcdB+ C. difficile
      strains in Korea, and these variant strains could evoke a higher rate of PMC than
      tcdA+tcdB+ strains.

PMID- 18082995
TI  - Patients' perspectives on sexual history taking in Korea.
AB  - OBJECTIVE: This study was conducted to assess patients' beliefs and attitudes
      towards physicians taking their sexual history during routine medical visits in
      Korea, where Confucianism is the core societal value. METHODS: A survey
      questionnaire was administered to determine the patients' perspectives to sexual
      history taking, their actual experience of being asked about sexual issues by
      physicians, their belief in the importance of sexual history taking, their
      attitudes and cooperativeness towards each component of sexual history, and the
      effect of the physicians' age and gender on their comfort level during interview.
      RESULTS: 74.6% of respondents had never been asked about their sexual issues by
      physicians. Most patients showed a positive attitude and cooperativeness in
      general, although more than 25% had a negative attitude and were uncooperative
      with regards to certain components of sexual issues. Their comfort level to
      sexual history taking was not influenced by the physicians' age. However, female
      patients felt more comfortable discussing sexual issues with female physicians.
      CONCLUSION: Sexual history taking was often overlooked during routine medical
      visits in Korea, although patients showed a relatively positive and cooperative
      attitude. Women showed a greater preference for female physicians. PRACTICE
      IMPLICATIONS: Sexual history taking should be more facilitated in clinical
      practice and requires a deliberate approach and skill.

PMID- 18082996
TI  - Improving consistency and quality of service delivery: implications for the
      addiction treatment field.
AB  - Addiction treatment providers face serious problems in delivering consistent,
      high-quality services over time. Among those providers with multiple treatment
      sites, there is also intersite variability. This is a serious problem in the
      addiction field, likely to be made worse as new technologies are introduced
      and/or as there is industry consolidation (Corredoira, R., Kimberly, J. (2006)
      Industry evolution through consolidation: Implications for addiction treatment.
      Journal of Substance Abuse Treatment 31, 255-265.). Although serious, these
      problems in managing and monitoring to assure consistent service quality have
      been faced by many other industries. Here, we review evidence from research in
      other industries regarding three different forms of management (vertical
      integration, franchising, and licensing) across a chain of individual service
      providers. We show how each management form affects the level, consistency, and
      improvement of service delivery over time. In addition, we discuss how such
      performance advantages affect customer demand as well as regulatory endorsement
      of the consolidated firm and its approach.

PMID- 18082997
TI  - Patient versus therapist alliance: whose perception matters?
AB  - Development of working alliance was examined for 25 opioid-abusing pain patients
      and their therapists. Patients participated in an eight-session intervention
      based on adherence strategies and employment of a supportive, psychoeducational
      approach; methadone was prescribed for pain. Treatment goals included opioid
      analgesic adherence and decreasing pain, functional interference, and substance
      abuse. Patients and therapists completed the Helping Alliance Questionnaire-II
      following each treatment session. At baseline, scores of patients and therapists
      indicated good alliance. Patient alliance grew significantly over time regardless
      of addiction severity and independent of treatment outcomes. In contrast,
      therapist alliance grew only for patients without substance abuse comorbidity
      and/or who had good outcomes. Patients' and therapists' alliance scores were
      consistent during sessions focused on emotional bonds but diverged during
      sessions that demanded behavior change, suggesting that therapists may have
      reacted negatively to patients' lack of progress. Whether therapists' reactions
      to poor performers impacted subsequent patient outcomes is unknown but should be
      investigated.

PMID- 18082998
TI  - Concurrent monitoring of psychological distress and satisfaction measures as
      predictors of addiction treatment retention.
AB  - Dropout from addiction services is common, and strategies to improve retention
      represent potentially important opportunities for quality improvement and
      treatment effectiveness. Identification of pretreatment predictors of dropout has
      not led to advances in treatment delivery. Via telephone monitoring, we examined
      the feasibility and predictive validity of weekly assessment of psychological
      distress and treatment satisfaction as factors potentially associated with
      retention and engagement over the initial 8 weeks of treatment. Participants
      included 107 addiction treatment patients, of whom 78% met criteria for 4 weeks
      of engagement and 59% were retained for 8 weeks. Of 8 weekly assessments, 63% of
      participants completed six or more calls. Baseline distress, baseline
      satisfaction, and change in distress over 4 weeks were not related reliably to
      treatment dropout or engagement. Decrease in satisfaction was significantly but
      modestly associated with low engagement. Implications for applications of weekly
      monitoring to improve retention are discussed.

PMID- 18082999
TI  - [Research on "usual care": the story of a defeat foretold].

PMID- 18083000
TI  - Evidence of increased reactive species formation by retinol, but not retinoic
      acid, in PC12 cells.
AB  - The biological effects of vitamin A (retinol) are generally ascribed to the
      activation of nuclear retinoid receptors by retinoic acid (RA), considered the
      most biologically active retinoid. However, it is not established whether the
      cytotoxic effects of vitamin A are due to retinoid receptors activation by RA.
      Vitamin A-related toxicity is associated with cellular redox modifications, often
      leading to severe oxidative damage, but the role of RA in this effect is also
      uncertain. We therefore studied the formation of intracellular reactive species
      induced by retinol and retinoic acid in PC12 cells, using an in vitro
      dichlorofluorescein (DCFH) fluorescence real-time assay. We observed that
      retinol, but not retinoic acid, induced a steady increase in DCF-based
      fluorescence over 60 min of incubation, and this increase was reversed by
      antioxidant (N-acetyl-cysteine and alpha-tocopherol) pre-treatment. This effect
      was also inhibited by the iron chelator 1,10-phenantroline and the impermeable
      calcium chelator EGTA. These results suggest that vitamin A-associated
      cytotoxicity is probably related to an oxidant mechanism dependent on iron and
      calcium, and the formation of intracellular reactive species is related to
      retinol, but not to RA.

PMID- 18083001
TI  - The evaluation of mate (Ilex paraguariensis) genetic toxicity in human
      lymphocytes by the cytokinesis-block in the micronucleus assay.
AB  - The present study evaluates the clastogenic and/or aneugenic potential of mate
      (Ilex paraguariensis) - previously tested for the presence of 48
      organophosphorous pesticides - in the culture of human lymphocytes in the absence
      of exogenous metabolic activation. Peripheral blood was obtained once from three
      healthy female donors for lymphocyte cell cultures. The cultures were treated
      with mate infusion (filtered in sterilized sartorius filter with a 0.22 mm pore
      membrane), distilled water (negative control), and 6 microg/ml bleomycin
      (positive control). For each experimental person, 3000 binucleated cells (BN)
      from two independent cultures (1000 cells from replicate cultures) were scored
      for the presence of micronuclei (MN). No statistical differences between mate
      infusion concentrations were observed: 1400 microg/ml (0.001+/-0.002), 700
      microg/ml (0.0006+/-0.0015), 350 microg/ml (0.002+/-0.002), 175 microg/ml
      (0.002+/-0.003) and negative control (0.001+/-0.001). The present findings show
      that there is no clastogenic or/and aneugenic basis underlying mate action in the
      CBMN assay.

PMID- 18083002
TI  - Microcystin-RR induced apoptosis in tobacco BY-2 suspension cells is mediated by
      reactive oxygen species and mitochondrial permeability transition pore status.
AB  - When tobacco BY-2 cells were treated with 60 microg/mL MC-RR for 5d, time
      dependent effects of MC-RR on the cells were observed. Morphological changes such
      as abnormal elongation, evident chromatin condensation and margination,
      fragmentation of nucleus and formation of apoptotic-like bodies suggest that 60
      microg/mL MC-RR induced rapid apoptosis in tobacco BY-2 cells. Moreover, there
      was a significant and rapid increase of ROS level before the loss of
      mitochondrial membrane potential (DeltaPsi(m)) and the onset of cell apoptosis.
      Ascorbic acid (AsA), a major primary antioxidant, prevented the increase of ROS
      generation, blocked the decrease in DeltaPsi(m) and subsequent cell apoptosis,
      indicating a critical role of ROS in serving as an important signaling molecule
      by causing a reduction of DeltaPsi(m) and MC-RR-induced tobacco BY-2 cell
      apoptosis. In addition, a specific mitochondrial permeability transition pores
      (PTP) inhibitor, cyclosporin A (CsA), significantly blocked the MC-RR-induced ROS
      formation, loss of DeltaPsi(m), as well as cell apoptosis when the cells were MC
      RR stressed for 3d, suggesting that PTP is involved in 60 microg/mL MC-RR-induced
      tobacco cell apoptosis signalling process. Thus, we concluded that the mechanism
      of MC-RR-induced apoptosis signalling pathways in tobacco BY-2 cells involves not
      only the excess generation of ROS and oxidative stress, but also the opening of
      PTP inducing loss of mitochondrial membrane potential.

PMID- 18083005
TI  - Deep brain stimulation of the anterior nucleus of the thalamus: effects of
      electrical stimulation on pilocarpine-induced seizures and status epilepticus.
AB  - PURPOSE: Electrical stimulation of the anterior nucleus of the thalamus appears
      to be effective against seizures in animals and humans. As the optimal
      stimulation settings remain elusive, we studied the effects of different
      stimulation parameters against pilocarpine induced seizures and status
      epilepticus (SE). METHODS: Adult rats had electrodes implanted bilaterally into
      the AN. Five days later, different groups of animals were stimulated with 1000
      microA, 500 microA, or 200 microA and frequencies of either 20 Hz or 130 Hz.
      Pilocarpine (350 mg/kg i.p.) was injected 5 min after stimulation onset and
      seizures were monitored. Sham-treated controls had electrodes implanted but did
      not receive stimulation until they developed SE. After SE, these animals had the
      electrodes turned on to assess whether AN stimulation could arrest ongoing ictal
      activity. RESULTS: Compared to sham-treated controls (n=8), stimulation at 500
      microA (n=13) significantly increased the latency for seizures and SE by 1.9-2.2
      fold. In contrast, stimulation at 1000 microA (n=8) produced a non-significant
      decrease in the latencies to these events. No major effect was observed with
      stimulation at 200 microA (n=11). Similar results were obtained for each current
      intensity, regardless of the stimulation frequency used (20 Hz and 130 Hz). In
      sham-treated controls that had the electrodes turned on after SE, stimulation was
      not able to arrest ongoing ictal activity. CONCLUSIONS: The anticonvulsant
      effects of AN stimulation against pilocarpine-induced seizures were mainly
      determined by the current and not the frequency of stimulation. AN stimulation
      initiated after SE onset was ineffective.

PMID- 18083004
TI  - Strain and age affect electroconvulsive seizure testing in rats.
AB  - Electroconvulsive seizure thresholds were compared between adolescent and mature
      Sprague--Dawley, Wistar, and Fischer rats. All strains had similar hindbrain or
      forebrain seizure thresholds as adolescents. As adults, hindbrain or forebrain
      seizure thresholds were highest for Sprague--Dawley and lowest for Fischer rats.
      Conversely, limbic seizure thresholds during adolescence were highest for Fischer
      rats. Additional study is needed to better delineate strain and maturational
      effects on electroconvulsive seizure testing.

PMID- 18083007
TI  - A large-scale validation study of the Medication Adherence Rating Scale (MARS).
AB  - Adherence to medication is an important predictor of illness course and outcome
      in psychosis. The Medication Adherence Rating Scale (MARS) is a ten-item self
      report measure of medication adherence in psychosis [Thompson, K., Kulkarni, J.,
      Sergejew, A.A., 2000. Reliability and validity of a new Medication Adherence
      Rating Scale (MARS) for the psychoses. Schizophrenia Research. 42. 241-247].
      Although initial results suggested that the scale has good reliability and
      validity, the development sample was small. The current study aimed to establish
      the psychometric properties of the MARS in a sample over four times larger. The
      scale was administered to 277 individuals with psychosis, along with measures of
      insight and psychopathology. Medication adherence was independently rated by each
      individual's keyworker. Results showed the internal consistency of the MARS to be
      lower than in the original sample, though adequate. MARS total score correlated
      weakly with keyworker-rated adherence, hence concurrent validity of the scale
      appeared only moderate to weak. The three factor structure of the MARS was
      replicated. Examination of the factor scores suggested that the factor 1 total
      score, which corresponds to the Medication Adherence Questionnaire [Morisky,D.E.,
      Green,L.W. and Levine,D.M., 1986. Concurrent and predictive validity of a self
      reported measure of medication adherence. Medical Care. 24, 67-74] may be a
      preferable measure of medication adherence behaviour to the total scale score.

PMID- 18083006
TI  - Increased striatal serotonin synthesis following cortical resection in children
      with intractable epilepsy.
AB  - BACKGROUND AND PURPOSE: Serotonin is a major regulator of structural brain
      plasticity, which may occur following cortical resection in humans. In this study
      we used positron emission tomography (PET) with alpha[11C]methyl-l-tryptophan
      (AMT) to evaluate serotonergic alterations in subcortical structures following
      cortical resection in children with intractable epilepsy. METHODS: AMT uptake in
      the thalamus and lentiform nucleus was evaluated postoperatively (1-89 months
      following resection) in 19 children (mean age: 8.7 years) with a previous
      cortical resection due to intractable epilepsy. Ten children with partial
      epilepsy but without resection and seven normal children served as controls.
      RESULTS: There was an increased AMT uptake in the lentiform nucleus ipsilateral
      to the resection as compared to the contralateral side (mean asymmetry: 4.2+/
      3.0%), and the asymmetries were significantly higher than those measured in the
      control groups (p<or=0.001). Post-resection asymmetry indices in the lentiform
      nucleus correlated inversely with postoperative time (r=-0.67; p=0.002), but not
      with age (p=0.29) or the extent of resection (p=0.77). In contrast, thalamic AMT
      uptake asymmetries were not different among the three groups (p=0.63).
      CONCLUSIONS: Cortical resection results in a sustained increase of AMT uptake in
      the lentiform nucleus, suggesting increased serotonin synthesis. Serotonergic
      activation in the deafferented striatum may play a role in the functional
      reorganization of cortico-striatal projections in humans.

PMID- 18083008
TI  - Reduction in epidermal Langerhans cells in patients with necrolytic migratory
      erythema.

PMID- 18083009
TI  - Occurrence of an SME-2-producing Serratia marcescens isolate in Canada.

PMID- 18083010
TI  - Role of the cell envelope in the antibacterial activities of polymyxin B and
      polymyxin B nonapeptide against Escherichia coli.
AB  - The role of membrane permeabilisation and disruption in the mechanism of action
      of some polymyxin analogues against Gram-negative organisms is contentious. The
      effects of polymyxin B (PMB) and its analogue polymyxin B nonapeptide (PMBN) on
      Escherichia coli envelopes should correlate, but previous work by other workers
      suggests that PMBN has a different mode of action. This study has reassessed the
      biochemical techniques used previously and has shown that, in contrast to
      previous studies, PMBN (a well-characterised antibacterial synergist) readily
      releases periplasmic proteins and lipopolysaccharide from treated E. coli at
      subinhibitory concentrations in normal physiological buffer conditions. We
      conclude that, when tested with appropriate methodology, PMBN closely correlates
      with the early effects of PMB on the cell envelope of E. coli and this study
      shows that it is now consistent with the accepted interactions of membrane-active
      agents against Gram-negative cells.

PMID- 18083011
TI  - Efficacy of voriconazole for Scedosporium apiospermum skull base osteomyelitis:
      case report and literature review.

PMID- 18083012
TI  - In vitro bactericidal activity of allicin combined with cefoperazone, tobramycin
      and ciprofloxacin.

PMID- 18083013
TI  - Executive deficits in psychotic and bipolar disorders - implications for our
      understanding of schizoaffective disorder.
AB  - OBJECTIVE: Schizoaffective disorder could be considered as a form of
      schizophrenia, a form of bipolar disorder, an independent disorder or a disorder
      intermediate between bipolar disorder and schizophrenia, within a psychotic
      continuum. The study of cognitive deficits in subjects with those diagnoses could
      help differentiate between these possibilities. METHODS: We compared cognitive
      performances of schizoaffective (SZAff) subjects with those of subjects with
      schizophrenia (SZ), bipolar disorder with psychotic symptoms (life-time) (BDP),
      bipolar disorder without life-time occurrence of psychotic symptoms (BD) and
      normal controls (NC). We used two tests of executive functions - the Wisconsin
      Card Sorting Test (WCST) and the Trail-making Test (TMT) - that are known to be
      impaired in those disorders. RESULTS: The number of perseverative errors on WCST
      was highest in SZ subjects and gradually decreased in SZAff, BDP and, finally in
      BD subjects. By contrast, SZ and SZAff subjects obtained similar scores in the
      TMT, as did BD and BDP patients. CONCLUSIONS: These results suggest that, for
      some deficits, there may be a continuum between SZ, SZAff and affective
      disorders, whereas SZAff patients most closely resemble SZ patients for other
      deficits. This implies that different conceptual views about schizoaffective
      disorder should be seen as complementary, rather than mutually exclusive.

PMID- 18083014
TI  - Tead4 is required for specification of trophectoderm in pre-implantation mouse
      embryos.
AB  - During pre-implantation mouse development, embryos form blastocysts with
      establishment of the first two cell lineages: the trophectoderm (TE) which gives
      rise to the placenta, and the inner cell mass (ICM) which will form the embryo
      proper. Differentiation of TE is regulated by the transcription factor Caudal
      related homeobox 2 (Cdx2), but the mechanisms which act upstream of Cdx2
      expression remain unknown. Here we show that the TEA domain family transcription
      factor, Tead4, is required for TE development. Tead1, Tead2 and Tead4 were
      expressed in pre-implantation embryos, and at least Tead1 and Tead4 were
      expressed widely in both TE and ICM lineages. Tead4-/- embryos died at pre
      implantation stages without forming the blastocoel. The mutant embryos continued
      cell proliferation, and adherens junction and cell polarity were not
      significantly affected. In Tead4-/- embryos, Cdx2 was weakly expressed at the
      morula stage but was not expressed in later stages. None of the TE specific
      genes, including Eomes and a Cdx2 independent gene, Fgfr2, was detected in Tead4
      /- embryos. Instead, the ICM specific transcription factors, Oct3/4 and Nanog,
      were expressed in all the blastomeres. Tead4-/- embryos also failed to
      differentiate trophoblast giant cells when they were cultured in vitro. ES cells
      with normal in vitro differentiation abilities were established from Tead4-/-
      embryos. These results suggest that Tead4 has a distinct role from Tead1 and
      Tead2 in trophectoderm specification of pre-implantation embryos, and that Tead4
      is an early transcription factor required for specification and development of
      the trophectoderm lineage, which includes expression of Cdx2.

PMID- 18083016
TI  - Sedentary behaviour and obesity development in children and adolescents.
AB  - Sedentary lifestyle patterns in children and adolescents, i.e. playing digital
      games, using computers and especially watching television, have been associated
      with obesity. However, not all sedentary behaviour has shown the same relevance
      to, and relationship with, obesity. Therefore, we conducted a review including
      published studies found in PubMed and other medical journals, dated between
      January 1990 and April 2007. The ages of the children and adolescents who were
      the object of the study ranged between 2 and 18 years. For the purpose of this
      paper, we selected cross-sectional, longitudinal and intervention studies.
      Sufficient evidence exists to recommend setting a limit to the time spent
      watching TV, especially for younger children. However, video games and computers
      do not represent such a high risk compared to watching TV, when they do not
      replace physical activity too much. In fact, there is no evidence to suggest that
      sedentary behaviour displaces physical activity levels. Mechanisms that explain
      the link between sedentariness and obesity are also discussed. Finally, future
      studies should take into account important mediators such as socioeconomic status
      and family structure.

PMID- 18083015
TI  - Novel propellant-driven inhalation formulations: engineering polar drug particles
      with surface-trapped hydrofluoroalkane-philes.
AB  - Challenges in reformulating pressurized metered-dose inhalers (pMDIs) with
      hydrofluoroalkane (HFA) propellants, and the potential of inhalation formulations
      for the delivery of drugs to and through the lungs have encouraged the
      development of novel suspension-based pMDI formulations. In this work we propose
      a new methodology for engineering polar drug particles with enhanced stability
      and aerosol characteristics in propellant HFAs. The approach consists in
      'trapping' HFA-philic moieties at the surface of particles, which are formed
      using a modified emulsification-diffusion method. The trapped moieties act as
      stabilizing agents, thus preventing flocculation of the otherwise unstable
      colloidal drug particles. This approach has advantages compared to surfactant
      stabilized colloids in that no free stabilizers remain in solution (reduced
      toxicity), and the challenges associated with the synthesis of well-balanced
      amphiphiles are circumvented. The methodology was tested by trapping polyethylene
      glycol (PEG) at the surface of particles of a model polar drug-salbutamol
      sulfate. Colloidal probe microscopy is used to quantitatively demonstrate the
      trapping of the HFA-phile at the surface, and the ability of PEG in screening
      particle-particle cohesive interactions. Both physical stability and the
      corresponding aerosol characteristics are significantly improved compared to
      those of a commercial formulation. The fine particle fraction of PEG-coated
      salbutamol sulfate was observed to be 42% higher than that of Ventolin HFA. The
      formation of stable dispersions of terbutaline hemisulfate using the same
      approach, suggests this to be a generally applicable methodology to polar drugs.

PMID- 18083017
TI  - Stearic acid potently modulates the activity of cyclooxygenase-1, but not
      cyclooxygenase-2, in the form of its CoA ester.
AB  - The effects of palmitic acid (PA), stearic acid (SA) and oleic acid (OA), and
      their respective CoA esters, PA-CoA, SA-CoA and OA-CoA, on the activities of
      cyclooxygenase (COX)-1 and -2 were examined. Ten units of purified COX-1 or -2
      were preincubated with drugs in the presence of hematin (0.1 microM) and phenol
      (2 mM) as cofactors for 10 min at 37 degrees C, and then incubated with 100
      microM arachidonic acid for 2 min at 37 degrees C. The amounts of prostaglandins
      formed were measured by HPLC. PA, SA and OA had no effect on the COX-1 and -2
      activities, but their respective CoA esters, PA-CoA, SA-CoA and OA-CoA,
      suppressed COX-1 activity with no significant effect on COX-2 activity. The
      inhibitory effect of SA-CoA was much stronger than that of PA-CoA and OA-CoA.
      These results suggest that SA has the potential to inhibit COX-1 activity, but
      not COX-2 activity, in the form of their CoA ester.

PMID- 18083019
TI  - Effect of incorrect use of dry powder inhalers on management of patients with
      asthma and COPD.
AB  - BACKGROUND: Incorrect usage of inhaler devices might have a major influence on
      the clinical effectiveness of the delivered drug. This issue is poorly addressed
      in management guidelines. METHODS: This article presents the results of a
      systematic literature review of studies evaluating incorrect use of established
      dry powder inhalers (DPIs) by patients with asthma or chronic obstructive
      pulmonary disease (COPD). RESULTS: Overall, we found that between 4% and 94% of
      patients, depending on the type of inhaler and method of assessment, do not use
      their inhalers correctly. The most common errors made included failure to exhale
      before actuation, failure to breath-hold after inhalation, incorrect positioning
      of the inhaler, incorrect rotation sequence, and failure to execute a forceful
      and deep inhalation. Inefficient DPI technique may lead to insufficient drug
      delivery and hence to insufficient lung deposition. As many as 25% of patients
      have never received verbal inhaler technique instruction, and for those that do,
      the quality and duration of instruction is not adequate and not reinforced by
      follow-up checks. CONCLUSIONS: This review demonstrates that incorrect DPI
      technique with established DPIs is common among patients with asthma and COPD,
      and suggests that poor inhalation technique has detrimental consequences for
      clinical efficacy. Regular assessment and reinforcement of correct inhalation
      technique are considered by health professionals and caregivers to be an
      essential component of successful asthma management. Improvement of asthma and
      COPD management could be achieved by new DPIs that are easy to use correctly and
      are forgiving of poor inhalation technique, thus ensuring more successful drug
      delivery.

PMID- 18083018
TI  - Atherosclerosis and systemic lupus erythematosus:   mechanistic basis of the
      association.
AB  - As patients with Systemic Lupus Erythematosus (SLE) live longer due to improved
      therapies and preventive measures, death and disability from cardiovascular
      events are increasing. Patients with SLE have an increased risk of
      atherosclerosis that persists even after accounting for traditional cardiac risk
      factors. Recent studies strongly suggest that the mechanism is due in part to a
      combination of inflammatory and immune mechanisms. Contributory factors include
      increased levels of oxidized lipids (such as oxidized LDL and pro-inflammatory
      HDL), upregulation of adhesion molecules, and upregulation of cytokines such as
      MCP-1, TNF-alpha, IFN-gamma, IL-1, and IL-12. Autoanitbodies to oxidized lipids
      and immune complexes may also play a role in the development of atherosclerosis
      in SLE. As in the pathogenesis of many lupus disease processes, the increased
      risk of atherosclerosis seen in SLE is likely due to the complex interplay of
      many of these inflammatory and immune mediators.

PMID- 18083020
TI  - Inspiratory capacity predicts mortality in patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) severity is usually
      graded upon the FEV(1) reduction and FEV(1) has been considered the most
      important mortality predictor with age in COPD. Recent studies suggest other
      factors as more powerfully related to mortality than FEV(1) in COPD patients.
      AIM: To assess the impact of inspiratory capacity (IC) on mortality and morbidity
      in COPD patients during a 5-year follow-up period. METHODS: We recruited 222
      patients with mild-to-moderate COPD from January 1995 to December 2001 with an
      average follow-up period of 60 months (range 30-114 months). Among different
      respiratory parameters measured in stable conditions FEV(1), FEV(1)/FVC%, IC and
      PaO(2), PaCO(2) and BMI were chosen and their relationships with all-cause and
      respiratory mortality and with morbidity were assessed. RESULTS: All these
      variables were associated with mortality at the univariate analysis. However, in
      a multivariate regression analysis (Cox proportional hazards model) for all-cause
      mortality age (year), IC (%pred.) and PaO(2) (mmHg) remained the only
      significant, independent predictors (HR=1.056, 95%CI: 1.023-1.091; HR=0.981,
      95%CI: 0.965-0.998; HR=0.948, 95%CI: 0.919-0.979, respectively). According to the
      same analysis, IC (%pred.) and PaO(2) (mmHg) were significant independent
      predictors for respiratory mortality (HR=0.967, 95%CI: 0.938-0.997; HR=0.919,
      95%CI: 0.873-0.969) together with FEV(1)/FVC% and BMI (kg/m(2)) (HR=0.967, 95%CI:
      0.933-1.022; HR=0.891, 95%CI: 0.807-0.985, respectively). IC (%pred.),
      FEV(1)/FVC%, and PaO(2) (mmHg) were also significantly related to morbidity, as
      independent predictors of hospital admissions because of exacerbations (OR=0.980,
      95%CI: 0.974-0.992; OR=0.943, 95%CI: 0.922-0.987; OR=0.971, 95%CI: 0.954-0.996,
      respectively). CONCLUSION: IC (%pred.) is a powerful functional predictor of all
      cause and respiratory mortality and of exacerbation-related hospital admissions
      in COPD patients.

PMID- 18083021
TI  - Leaching of wood ash products aimed for spreading in forest floors--influence of
      method and L/S ratio.
AB  - Use of biofuels in the form of logging residues is increasing in the European
      countries. This intensive forestry, where entire trees are removed from the
      felling sites, may contribute to a negative nutrient balance in the forest soil.
      Recycling of ash from the combustion of clean wood fuel, sometimes in combination
      with limestone or additives/binders, back into the forest soil could maintain the
      soil nutrient reservoir intact. Before spreading ash, it is important to
      determine its contents and, particularly, its decomposition pattern using
      reliable laboratory leaching tests. In this study, mineralogy and the leaching of
      Na, Ca, K, Mg, Mn, Al, Cu, Fe, P, and Zn from wood ash pellets and granules,
      produced both from green liquor sludge and fly ash, are examined by XRD and by
      subjecting these substances to three different laboratory leaching tests: upflow
      percolation (CEN/TS 14405), batch leaching (SS-EN12457), and a new Swedish
      leaching test using a magnetic stirrer. Mineral phases such as quartz,
      ettringite, calcite, gehlenite, and aphtitalite were identified in the ash
      granules and in the ash/green liquor sludge granules, by means of XRD. Six
      additional minerals were detected in the granules of ash only, and another six in
      the ash/green liquor sludge granules. At L/S 2, the batch leaching test resulted
      in the highest amounts of elements leached and the upflow percolation test the
      lowest. At L/S 10, both the batch leaching test and the upflow percolation test
      resulted in high amounts of elements leached. The batch leaching test at L/S 10
      complies quite well with the percolation test and could be suitable for ash/green
      liquor sludge granule evaluation in daily practice. The magnetic stirrer test
      seems to underestimate the release potential of elements from granules. The batch
      test is simple to perform, and has the ability to dissolve 70-80% of the elements
      with the highest mobility from the materials under study.

PMID- 18083022
TI  - Do cancer predictions work?
AB  - Two different types of simple extrapolation models were investigated as tools for
      cancer incidence prediction. The number of incident cancer cases by sex and site
      in Finland was predicted using a prediction interval for each year from 1967 to
      2003 on the basis of historical cancer incidence data obtained 5 to 15 years
      earlier. Cancer sites where major human-made changes in aetiology and diagnostics
      had occurred were analysed separately. Assuming that such changes had not
      occurred, the 95% prediction intervals based on normal errors of the age
      standardised rate and on Poisson models included the observed number in 65-100%
      of the years. The Poisson models produced, on average, shorter intervals and were
      more capable of indicating a site where the model assumptions did not hold true.
      Simple extrapolation models may be used with some caution on coverage when there
      are no known factors that might make abrupt changes in the temporal development
      of cancer incidence. On the other hand, they may be used for detecting the
      effects of such factors.

PMID- 18083023
TI  - Effects of fulvestrant 750mg in premenopausal women with oestrogen-receptor
      positive primary breast cancer.
AB  - Fulvestrant (Faslodex) is a pure anti-oestrogen that reduces markers of hormone
      sensitivity and proliferation in postmenopausal women with oestrogen-receptor
      (ER)-positive breast cancer. This randomised trial compared the effects on the
      tumours of a single dose of 750mg fulvestrant to those of daily tamoxifen (20mg)
      taken 14-16 days prior to surgery in 60 premenopausal women with ER-positive
      primary breast cancer. There were statistically significant falls in the
      expression of ER and Ki67 levels compared to the baseline with both drugs. Both
      drugs caused a decrease in PgR expression from baseline but this was only
      statistically significant with fulvestrant. No statistically significant
      differences were seen between the two treatment groups. Fulvestrant caused an
      increase in circulating levels of oestradiol, irrespective of the stage of the
      menstrual cycle at which patients commenced treatment. No major changes were seen
      in LH, FSH and progesterone levels with either drug. The most common adverse
      events with fulvestrant were headaches, hot flushes, nausea and disturbance of
      menses. Contrary to previous studies with fulvestrant 250mg, these findings
      suggest that at a dose of 750mg fulvestrant is effective at reducing the effects
      of oestrogen on ER-positive breast cancer in premenopausal women.

PMID- 18083024
TI  - Hydrogen and polyhydroxybutyrate producing abilities of microbes from diverse
      habitats by dark fermentative process.
AB  - Thirty five bacterial isolates from diverse environmental sources such as
      contaminated food, nitrogen rich soil, activated sludges from pesticide and oil
      refineries effluent treatment plants were found to belong to Bacillus,
      Bordetella, Enterobacter, Proteus, and Pseudomonas sp. on the basis of 16S rRNA
      gene sequence analysis. Under dark fermentative conditions, maximum hydrogen
      (H(2)) yields (mol/mol of glucose added) were recorded to be 0.68 with
      Enterobacter aerogenes EGU16 followed by 0.63 with Bacillus cereus EGU43 and
      Bacillus thuringiensis EGU45. H(2) constituted 63-69% of the total biogas
      evolved. Out of these 35 microbes, 18 isolates had the ability to produce
      polyhydroxybutyrate (PHB), which varied up to 500 mg/l of medium, equivalent to a
      yield of 66.6%. The highest PHB yield was recorded with B. cereus strain EGU3.
      Nine strains had high hydrolytic activities (zone of hydrolysis): lipase (34-38
      mm) -Bacillus sphaericus strains EGU385, EGU399 and EGU542; protease (56-62 mm) 
      Bacillus sp. strains EGU444, EGU447 and EGU445; amylase (23 mm) -B. thuringiensis
      EGU378, marine bacterium strain EGU409 and Pseudomonas sp. strain EGU448. These
      strains with high hydrolytic activities had relatively low H(2) producing
      abilities in the range of 0.26-0.42 mol/mol of glucose added and only B.
      thuringiensis strain EGU378 had the ability to produce PHB. This is the first
      report among the non-photosynthetic microbes, where the same organism(s) -B.
      cereus strain EGU43 and B. thuringiensis strain EGU45, have been shown to produce
      H(2) - 0.63 mol/mol of glucose added and PHB - 420-435 mg/l medium.

PMID- 18083025
TI  - Optimisation of biodegradation conditions for the treatment of olive mill
      wastewater.
AB  - The aim of the present paper was to optimise the conditions of aerobic treatment
      of olive mill wastewater. To do so, the waste was treated following the
      experimental optimal design methodology studying the set of factors susceptible
      to influence the treatment (pH, C/N ratio, aeration and temperature). The results
      of a first series of experiments showed a strong correlation between the
      reduction in the levels of polyphenols and three of the parameters studied, i.e.
      the C/N ratio, aeration and temperature. Optimised conditions led to a 94% drop
      in polyphenols. Then, for a finer study of the conditions, just two parameters
      were varied, the pH and the C/N ratio. The results showed that the conditions of
      pH modification (addition of lime or sodium hydroxide) and the C/N ratio (urea or
      ammonium nitrate) allowed the microbiological activity to be very significantly
      improved. This led to polyphenol reductions of 51% and 76%.

PMID- 18083026
TI  - Gasification of biomass/high density polyethylene mixtures in a downdraft
      gasifier.
AB  - In this work, an experimental study of the thermal decomposition of mixtures of
      wood particles and high density polyethylene in different atmospheres has been
      carried out in a downdraft gasifier with a nominal processing capacity of 50
      kg/h. The main objective was to study the feasibility of the operation of the
      gasification plant using mixtures and to investigate the characteristics of the
      gas obtained. In order to do so, experiments with biomass only and with mixtures
      with up to 15% HDPE have been carried out. The main components of the gas
      generated are N(2) (50%), H(2) (14%), CO (9-22%) and CO(2) (7-17%) and its
      relatively high calorific value was adequate for using it in an internal
      combustion engine generator consisting of a modified diesel engine coupled with a
      25 kV A alternator.

PMID- 18083027
TI  - In silico screening and biological evaluation of inhibitors of Src-SH3 domain
      interaction with a proline-rich ligand.
AB  - Src signalling and transduction are directly involved in cell growth, cell cycle,
      malignant transformation and cell migration, providing therapeutic opportunities
      through inhibition of Src. Here we report virtual screening for novel compounds
      that inhibit the Src-SH3 protein-protein interaction with a proline-rich peptide
      ligand. Computational docking of the ZINC compound database was performed using
      GOLD. Top-scoring compounds were assayed using a fluorescence polarization-based
      assay. A benzoquinoline derivative showed micromolar inhibition of binding
      between Src-SH3 and the proline-rich peptide. Several analogues were subsequently
      assayed showing the requirement of a linker between the benzoquinoline and phenyl
      rings, and electron donating substituents on the phenyl ring.

PMID- 18083028
TI  - Synthesis and biological evaluation of bengacarboline derivatives.
AB  - Novel derivatives of the marine alkaloid bengacarboline have been synthesized.
      The seco derivatives 11 and 12 were evaluated for topoisomerase inhibition, DNA
      damages, cytotoxicity and cell cycle perturbation. The two synthetic analogs are
      more potent cytotoxic agents than bengacarboline and they both induce an
      accumulation of cells in the S phase of DNA synthesis. They do not function as
      topoisomerase inhibitors but trigger DNA damages in cells.

PMID- 18083029
TI  - Report on the sixth scientific meeting of the Australasian Society for Breast
      Disease (ASBD).

PMID- 18083030
TI  - Sunburned skin activates inflammasomes.
AB  - Ultraviolet (UV) irradiation injures the epidermis, resulting in sunburn and
      inflammation. UV-irradiated keratinocytes secrete interleukin-1beta through a
      caspase-1-dependent mechanism. In seeking a link between UV-irradiation and
      caspase-1 activation, a prominent role for the NOD-like receptor (NLR) family of
      innate immunity proteins was discovered recently. NLRs activate caspases through
      the assembly of macromolecular complexes called 'inflammasomes.' Although the
      mechanism by which UV-irradiation activates inflammasomes remains obscure, these
      recent findings shed light on NLRs as intermediaries between cell injury and
      inflammation.

PMID- 18083031
TI  - Postural control deficit in acute QTF grade II whiplash injuries.
AB  - STUDY DESIGN: Experimental in vivo study. OBJECTIVE: The objective was to
      investigate the balance control in patients with acute QTF grade II whiplash
      injuries of the cervical spine. SUMMARY OF BACKGROUND DATA: Tetra-ataxiametric
      posturography in chronic pain patients after whiplash injuries of the cervical
      spine has revealed an impaired regulation of balance. However, so far it is
      unclear if this is caused by the accident or other factors that are associated
      with the pain chronification process. METHODS: 40 patients with acute QTF grade
      II whiplash injuries and 40 healthy matched controls were examined on a
      posturography platform. The stability index ST(Sigma) and the Fourier analysis
      FA(Sigma) (0.10-1.00Hz) were established for eight standing positions and sum
      scores were calculated. The pain index was established using a visual analog
      scale ranging from 0 to 100. A follow-up examination was conducted for the
      patients after 2 months. RESULTS: The patients with acute whiplash injuries of
      the cervical spine achieved significantly poorer results for both ST(Sigma) and
      FA(Sigma) than the healthy controls. There were no differences between the eight
      standing positions for both ST(Sigma) and FA(Sigma). After 2 months, 17 patients
      had no change in the pain development, 21 patients showed an improvement in pain
      intensity and 2 patients had deteriorated. The subgroup of patients with
      improvement in pain intensity showed a significant improvement in balance control
      concerning the FA(Sigma) compared to patients with unchanged pain intensity.
      CONCLUSION: Patients with acute whiplash injuries have a reduced balance control
      as compared to matched controls. This study gives an indication that post
      traumatic neck pain is associated with impairments of postural control.

PMID- 18083032
TI  - Centipede and inchworm models to explain Mycoplasma gliding.
AB  - The twelve Mycoplasma species known to glide on solid surfaces all lack surface
      flagella or pili, and no genes homologous to known motility systems have been
      found in the five genomes sequenced to date. Recent studies on the fastest of
      these species, M. mobile, examined novel proteins involved in the gliding
      mechanism, binding targets on the solid surfaces, energy sources and mechanical
      characteristics of the movements. Accordingly, I propose a working model for the
      gliding mechanism, called the centipede (power stroke) model, in which the 'leg'
      proteins repeat a cycle of binding to and release from the solid surface, using
      energy from ATP. Another 'inchworm model' suggested from the structural studies
      of a human pathogen, M. pneumoniae, is also discussed.

PMID- 18083033
TI  - IRES-mediated pathways to polysomes: nuclear versus cytoplasmic routes.
AB  - Eukaryotic mRNA initiates translation by cap-dependent scanning, ribosome
      shunting and cap-independent internal ribosome entry. Internal ribosome entry was
      first discovered for cytoplasmic RNA viruses but has also been identified for DNA
      viruses and cellular mRNAs. An internal ribosome entry site (IRES) directs
      internal binding of ribosomes and nucleates the formation of a translation
      initiation complex. Current research is aimed at identifying interactions between
      IRES elements and RNA-binding proteins known as ITAFs (IRES trans-acting
      factors). Here we compare IRES elements from cytoplasmic RNA viruses with those
      of cellular mRNAs and DNA viruses with nuclear mRNA synthesis, and suggest that
      ITAF composition and IRES function directly reflect the site of synthesis of mRNA
      and the history of its pathway to polysomes.

PMID- 18083034
TI  - Functional assay and structure-activity relationships of new third-generation P
      glycoprotein inhibitors.
AB  - Twenty-eight compounds, including 24 structurally related derivatives of
      tariquidar synthesized in our laboratory, and four XR compounds, reported by
      Xenova group Ltd, were investigated by the Hoechst 33342 and Calcein AM
      functional assays for estimation of their inhibitory effects on the transport
      activity of P-glycoprotein (P-gp). A high correlation between the effects
      obtained in both assays was observed at the substrate concentrations used. The
      analyses of kinetics data from experiments at different substrate concentrations
      revealed non-competitive inhibition in the Calcein AM assay and competitive
      inhibition in the Hoechst 33342 assay. The 3D structures of the compounds were
      further aligned on Hoechst 33342 using flexible and pharmacophore alignments. The
      results suggested that inhibitors could interact with the H-binding site of P-gp
      and this could potentially be achieved by different ways of binding. The best 3D
      QSAR models, generated by CoMFA and CoMSIA, yielded an internal predictive
      squared correlation coefficient higher than 0.8 and included electrostatic,
      steric, hydrogen bond acceptor, and hydrophobic fields. Validation of the models
      on an external test set of 30 XR compounds gave predictive squared correlation
      coefficients of up to 0.66. An excellent correspondence between the experimental
      and modeled activities of the test compounds was observed. The models can be used
      for prediction and rational design of new P-gp inhibitors.

PMID- 18083035
TI  - Imidazolidines as new anti-Trypanosoma cruzi agents: biological evaluation and
      structure-activity relationships.
AB  - Imidazolidine derivatives were studied as anti-Trypanosoma cruzi agents.
      Imidazolines can be considered as ethylenediamine/carbonyl precursors and
      therefore interfere with the biosynthesis of polyamines into the parasite. Some
      of the derivatives were found to have high and selective activity against the
      proliferative stages of the parasite, with IC(50) values against the epimastigote
      form in the low micromolar range as the reference drug Nifurtimox. The
      imidazolidines demonstrated to be stable after five days of incubation in buffer
      glucose, pH 7, indicating that diamines were not obtained in these conditions.
      But it was found that two of the studied diamine precursors were as active as the
      parent compounds. Probably, the imidazolidines affect the mitochondrial integrity
      according to the excreted end-products found in the NMR studies. The QSAR studies
      indicated that the bioactivities are correlated with the lipophilicities. In
      conclusion, we have described a new and relevant bioactivity for imidazolidines.
      The results support further in vivo studies of some of these imidazolidine
      derivatives.

PMID- 18083036
TI  - Structure-activity study of 2,3-benzodiazepin-4-ones noncompetitive AMPAR
      antagonists: identification of the 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8
      ethylenedioxy-4H-2,3-benzodiazepin-4-one as neuroprotective agent.
AB  - In the search for AMPA receptor (AMPAR) antagonists, 2,3-benzodiazepines
      represent a family of specific noncompetitive antagonists with anticonvulsant and
      neuroprotective properties. We have previously shown that 2,3-benzodiazepin-4
      ones possess marked anticonvulsant properties and high affinity for the
      noncompetitive binding site of the AMPAR complex. In this paper, we report the
      synthesis and pharmacological characterization of a full set of 2,3-benzodiazepin
      4-ones in order to better define the structure-activity relationship (SAR) of
      this class of compounds. Binding assays and functional tests were performed to
      evaluate the antagonistic activity at the AMPARs. Through these results we have
      identified a potent AMPAR antagonist, 1-(4-amino-3-methylphenyl)-3,5-dihydro-7,8
      ethylenedioxy-4H-2,3-benzodiazepin-4-one (5c). This compound noncompetitively
      inhibited AMPAR-mediated toxicity in primary mouse hippocampal cultures with an
      IC(50) of 1.6muM and blocked kainate-induced calcium influx in rat cerebellar
      granule cells with an IC(50) of 6.4muM. Thus, 5c has the in vitro potential as
      therapeutic drug in the treatment of various neurological disorders.

PMID- 18083037
TI  - Monoolein and chitosan gels as potential carriers of the rhBMP-2, using
      decortication surgical technique in Wistar rats as experimental model.
AB  - The purpose of this work was to evaluate the new bone tissue, comparing two
      different carriers for rhBMP-2, monoolein and chitosan gels, using the
      decortication and nondecorticatication surgical technique in rat mandibles,
      evaluated by histomorphometrical method. It was used 56 male Wistar rats (300 g),
      divided into 8 groups according to the rhBMP-2 carrier used, monoolein or
      chitosan gels; surgical technique, bone decortication or nondecortication; and
      period of time, 3 or 6 weeks until the sacrifice by perfusion. Results obtained
      in this study showed that the rhBMP-2/monoolein and rhBMP-2/chitosan used in this
      experimental model was able to induce osteogenesis, contributing to the bone
      healing process. The bone repair process was time dependent, so that at 6 weeks
      there was an improved amount of new bone in relation to 3 weeks, considered each
      analyzed group, and the decortication was able to expose the bone marrow and
      speed up the bone healing process, which was showed by histomorphometrical
      methods. Both of carriers were capable to adapt to the bone surgical area,
      according to the clinical observations, and had favorable properties in relation
      to protein releasing, revealed by the amount of new bone tissue found in the
      histological analysis.

PMID- 18083038
TI  - Production of the therapeutic radionuclides 193mPt and 195mPt with high specific
      activity via alpha-particle-induced reactions on 192Os.
AB  - For the production of therapy-relevant radionuclides (193m)Pt (T(1/2)=4.33 d) and
      (195m)Pt (T(1/2)=4.03 d) with a high specific activity, the
      (192)Os(alpha,n)(195m)Pt and (192)Os(alpha,3n)(193m)Pt nuclear reactions were
      investigated for the first time from their respective thresholds up to 28 MeV.
      Thin samples of enriched (192)Os were prepared by electrodeposition on Ni, and
      the conventional stacked-foil technique was used for cross-section measurements.
      The calculated thick target yields were found to be 0.013 MBq/microA h for the
      (192)Os(alpha,n)(195m)Pt reaction in the energy range of E(alpha)=24-->18 MeV,
      and 0.25 MBq/microA h for the (192)Os(alpha,3n)(193m)Pt reaction in the energy
      range of E(alpha)=28-->24 MeV. The two radionuclides could not be detected in the
      interactions of (3)He particles with (192)Os. A production method involving high
      current alpha-particle irradiation of enriched (192)Os and efficient chemical
      separation of radioplatinum was developed. Batch yields of about 1 MBq (195m)Pt
      and 8.7 MBq (193m)Pt were achieved. Compared to the reactor production these
      batch yields are very low, but the (192)Os(alpha,n)(195m)Pt and
      (192)Os(alpha,3n)(193m)Pt reactions are superior with respect to the specific
      activity of the products which is higher by two orders of magnitude.

PMID- 18083039
TI  - The Shelhigh No-React bovine internal mammary artery: a questionable alternative
      conduit in coronary bypass surgery?
AB  - BACKGROUND: Increasing age and comorbidities among patients undergoing coronary
      artery bypass surgery (CABG) stimulates the exhaustive research for alternative
      grafts. No-React treatment should render the tissue resistant against
      degeneration and reduce early inflammatory response. The aim of the present study
      was an invasive assessment of the patency of No-React bovine internal mammary
      artery (NRIMA grafts) used as bypass conduit in CABG surgery. PATIENTS AND
      METHODS: Nineteen NRIMA grafts were used in 17 patients (2.9%) out of a total of
      572 patients undergoing CABG surgery within a 12-month period. All intraoperative
      data were assessed and in-hospital outcome was analysed. Follow-up examination
      was performed 7.0+/-4.0 months after initial surgery, including clinical status
      and coronary angiography to assess patency of the NRIMA grafts. RESULTS: Average
      perioperative flow of all NRIMA grafts was 71+/-60 ml/min. One patient died in
      hospital due to a multi-organ failure. Four patients refused invasive assessment.
      Follow-up was complete in 12 patients with overall 13 NRIMA grafts. Nine NRIMA
      grafts (69.2%) were used for the right coronary system, two NRIMA grafts (15.4%)
      on the LAD and two on the circumflex artery. Graft patency was 23.1% and was
      independent of the intraoperative flow measurement. CONCLUSIONS: NRIMA grafts
      show a very low patency and cannot be recommended as coronary bypass graft
      conduits. Patency was independent of the perioperative flow, assessed by Doppler
      ultrasound. Because of this unsatisfying observation, this type of graft should
      be utilised as a last resource conduit and used only to revascularise less
      important target vessels, such as the end branches of the right coronary artery.

PMID- 18083040
TI  - Perivascular tissue of internal thoracic artery releases potent nitric oxide and
      prostacyclin-independent anticontractile factor.
AB  - OBJECTIVE: It has been recently suggested that perivascular tissue (PVT) releases
      hypothetic adipocyte- or adventitia-derived relaxing factor. The aim of the study
      was to assess anticontractile properties of perivascular tissue of human internal
      thoracic artery (ITA) and to check if this activity is nitric oxide (NO)- or
      prostacyclin-dependent. We also analyzed the influence of pleural adipose tissue
      on ITA reactivity. METHODS: Human ITA rings were studied in vitro. First,
      skeletonized and pedicled ITA reactivity to serotonin and angiotensin II was
      compared. In subsequent experiments fragments of ITA were skeletonized and
      divided into two preparations. One was incubated alone, the other together with
      PVT or pleural adipose tissue floating freely in the bath. First, concentration
      response curves to either serotonin or angiotensin II were constructed. Tissue
      was then transferred from one bath to the other and concentration-response curves
      were reconstructed. The same protocol was applied with the inhibition of NO
      synthase with L-NMMA (10(-4)M) and cyclooxygenase with indomethacin (10(-5)M).
      RESULTS: Skeletonization augmented contractile response to serotonin (E(max)
      16.6+/-1.85 mN vs 43.8+/-3.87 mN; pedicled vs skeletonized ITA, respectively;
      p<0.001) and angiotensin II (E(max) 10.9+/-1.07 mN vs 26.6+/-1.45 mN,
      respectively; p<0.001). PVT presence in the bath caused decrease of E(max) from
      40.8+/-5.01 to 20.1+/-2.69 mN for serotonin; p<0.001 and from 31.4+/-3.75 to
      13.0+/-1.60 mN for angiotensin II, p<0.001 (PVT(-) vs PVT(+), respectively). PVT
      did not change ITA sensitivity (EC(50)) to serotonin or angiotensin II. Pleural
      adipose tissue did not change the contractile response of ITA to serotonin
      (E(max) 37.2+/-4.95 mN vs 36.3+/-4.83 mN, pleural fat+and pleural fat-,
      respectively; p=0.9). NO and prostacyclin inhibition failed to abolish
      anticontractile properties of perivascular tissue. PVT with cyclooxygenase and NO
      synthase inhibition decreased E(max) of serotonin from 46.6+/-3.03 to 28.2+/-4.02
      mN, p<0.001 and E(max) of angiotensin II from 27.2+/-2.00 to 16.4+/-2.10 mN,
      p<0.001. CONCLUSIONS: Perivascular tissue of ITA releases potent, soluble, nitric
      oxide and prostacyclin-independent anticontractile factor. The pleural adipose
      tissue does not influence ITA reactivity to vasoconstrictors. Preservation of
      perivascular tissue may protect against vasospasm of ITA graft in clinical
      settings.

PMID- 18083041
TI  - Clinical significance and treatment of skin rash from erlotinib in non-small cell
      lung cancer patients: results of an Experts Panel Meeting.
AB  - Advances in the knowledge of tumor biology and mechanisms of oncogenesis has
      granted the singling out of several molecular targets for non-small cell lung
      cancer (NSCLC) treatment. Among these targets, epidermal growth factor receptor
      (EGFR), or HER1, has received particular attention in lung cancer treatment.
      Erlotinib, an orally available inhibitor of EGFR tyrosine kinase in a phase III
      randomized placebo-controlled trial (BR.21), has been proven to prolong survival
      in NSCLC patients after first or second line chemotherapy. Skin rash is the most
      common adverse event associated with erlotinib treatment and it is often cause of
      negative impact on patients' quality of life. There is no specific treatment for
      this toxicity due to the lack of evidence-based data and recommendations. A panel
      of Italian oncologists, who had participated to clinical trials and to the
      Expanded Access Program for erlotinib in NSCLC treatment, and dermatologists with
      experience with cutaneous toxicity from EGFR inhibitors, attended a Meeting held
      in Rome on December 2006 to discuss skin rash from erlotinib and to provide
      suggestions for managing this frequent side-effect.

PMID- 18083043
TI  - RANTES (CCL5) potentiates calcium ionophore in the production of LTB4 in rat
      adherent macrophages from granuloma induced by KMnO4: inhibiton by NDGA.
AB  - The activation of monocytes/macrophages by several stimuli is an initial event in
      the inflammatory response. To ascertain the importance of LTB(4) and 5
      lypoxigenase in the inflammatory site, we isolated and stimulated rat adherent
      granuloma macrophages (RAGMs) with calcium ionophore in the presence or absence
      of regulated on activation, normal T expressed and secreted (RANTES) [CCL5] at
      different concentrations. We tested the hypothesis that RANTES may influence the
      production of LTB(4) stimulated by calcium ionophore A23187 (2.5 microM/ml) in
      rat adherent granuloma macrophages derived from granuloma induced by potassium
      permanganate diluted 1:40 saturated solution. To test this hypothesis, we
      measured LTB(4) production, in rat granuloma macrophages stimulated with A23187
      (2.5 microM) alone and in combination with RANTES at different concentrations. In
      these studies, the cell-free supernatant of stimulated RAGMs with the ionophore
      A23187, resulted in a drastic increase of LTB(4). However, when the cells were
      treated with the combination RANTES plus A23187 the stimulatory effect was more
      pronounced than A23187 alone. LTB(4) production was quantitated. The calcium
      ionophore A23187 directly induced LTB(4) in macrophages, this production was
      markedly enhanced when the cells were pretreated with RANTES. However, the
      addition of RANTES in the absence of calcium ionophore A23187 did not directly
      induce LTB(4) release, nor was lypoxigenase expression augmented. Preincubation
      of RAGMs with NDGA (nordihydroguiaretic acid) (10(-5)M) completely abolished the
      production of LTB4 on RAGMSs challenged with A23187 in combination with RANTES or
      A23187 alone in the supernatants. Similar effects were obtained when the cells
      were pretreated with dexamethasone. These data suggest, for the first time, that
      RANTES may stimulate the release of LTB(4), only when it is associated to other
      stimuli and for this reason we conclude that RANTES modulates inflammatory
      diseases, and may require other stimuli to be effective in amplifying its
      spectrum of action(s).

PMID- 18083042
TI  - Characterization of synovial cell clones isolated from rheumatoid arthritis
      patients: possible involvement of TNF-alpha in reduction of osteoprotegerin in
      synovium.
AB  - To elucidate the role of the synovium in bone destruction by osteoclasts in
      rheumatoid arthritis (RA), primary synovial cells isolated from RA patients were
      cultured and characterized. The cultured primary cells did not produce RANKL
      (TRANCE/ODF/OPGL/TNFSF11/CD254), an inducer of osteoclast differentiation, but
      constitutively produced its inhibitor, osteoprotegerin (OPG). Addition of TNF
      alpha to the primary cultures of synovial cells reduced the cell viability and
      strongly suppressed OPG production. We then established nine synovial cell
      clones, including SYM-1, responsible for OPG production from primary synovial
      cell cultures. TNF-alpha induced apoptosis of SYM-1 cells within 24h and
      decreased OPG levels, while infliximab, a chimerical form of the anti-TNF-alpha
      antibody drug, suppressed the apoptosis and restored OPG levels. These results
      suggest the existence of fibroblastic cells producing OPG in the synovium, while
      TNF-alpha suppresses OPG production by inducing apoptosis in those cells.
      Further, infliximab is considered to inhibit bone destruction through restoration
      of OPG levels in RA.

PMID- 18083044
TI  - TRAIL in the mandarin fish Siniperca chuatsi: gene and its apoptotic effect in
      HeLa cells.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is one of
      the TNF superfamily members, participating in many biological processes including
      cell proliferation and apoptotic death. In this study, a TRAIL gene was cloned
      from a perciform fish, the mandarin fish Siniperca chuatsi, a major cultured fish
      in China's aquaculture, and is named as SCTRAIL for S. chuatsi TRAIL. The full
      length cDNA of SCTRAIL is 1359bp, encoding a 283-amino-acid protein. This deduced
      protein contains the Cys(231), a 23-mer fragment of transmembrane region, a
      glycosylation site and a TNF family signature, all of which are conserved among
      TRAIL members. SCTRAIL gene consists of six exons, with five intervening introns,
      spaced over approximately 9kb of genomic sequence. Southern blotting demonstrated
      that the SCTRAIL gene is present as a single copy in mandarin fish genome. A
      620bp promoter region obtained by genome walking contains a number of putative
      transcription factor binding sites, such as Oct-1, Sp-1, NF-1, RAP-1, C/EBPalp,
      NF-kappaB and AP-1. The SCTRAIL is constitutively expressed in all the analyzed
      tissues, as revealed by RT-PCR, which is confirmed by Western blotting analysis
      using polyclonal antibody against bacteria-derived recombinant SCTRAIL protein.
      As an apoptosis-inducing ligand, the overexpression of SCTRAIL but not the mutant
      SCTRAIL-C203S in HeLa cells induced changes characteristic of apoptosis,
      including chromatin condensation, nucleus fragmentation, DNA ladder, and increase
      of sub-G0/G1 cells in FACS analysis.

PMID- 18083045
TI  - Anti-lipopolysaccharide factors from the black tiger shrimp, Penaeus monodon, are
      encoded by two genomic loci.
AB  - Different isoforms of the ALF homologues (ALFPm1-5) have been previously
      identified from Penaeus monodon expressed sequence tag (EST) database
      (http://pmonodon.biotec.or.th). The nucleotide and amino acid sequences of the P.
      monodon ALF homologues were analyzed and categorized into two groups, ALFPm1 and
      2 in group A and ALFPm3-5 in group B. The genomic sequences of the two ALF gene
      groups were obtained by using the PCR and genome walking techniques. The ALF
      group A gene consisted of three exons interrupted by two introns whereas the ALF
      group B gene contained four exons interrupted by three introns. The alignment of
      genomic sequences with the ALF cDNA sequences revealed that different transcripts
      in both groups were generated by alternative RNA splicing of the pre-mRNA
      transcripts. The 5' upstream sequences of the two ALF groups contained the
      putative cis-regulatory elements, including the activator protein 1, the Octamer,
      the GATA, the nuclear factor-kappaB, and the GAAA motifs, which possibly promoted
      transcription in response to infection as in other antimicrobial peptide genes.
      The RT-PCR analysis revealed that although all ALF isoforms were expressed in
      individual shrimp, the ALFPm2 and 3 were the major or authentic ALFs in the
      hemocytes. The expression of both ALFPm2 and 3 were increased in response to
      Vibrio harveyi infection indicating the important function of the ALFs against
      bacterial invasion.

PMID- 18083046
TI  - Effects of the marine toxins okadaic acid and palytoxin on mussel phagocytosis.
AB  - The present study analyzes the effects of the marine toxins okadaic acid (OA) and
      palytoxin (PTX) on the phagocytic activity of immunocytes from the mussel Mytilus
      galloprovincialis. In particular, we describe how the effects of the two
      biotoxins are influenced by the temperature and experimental stress applied
      before hemolymph withdrawal. The collected data indicate that OA increases
      phagocytic activity only when hemolymph incubation is performed at 25 degrees C,
      but not at 20 degrees C, suggesting a certain degree of dependence of OA effects
      from the status of mussel immunocytes. Conversely, PTX plays an active role in
      immunocyte signalling transduction pathways, increases the phagocytic activity
      and markedly promotes the involvement of p38 mitogen-activated protein (MAP)
      kinase in phagocytosis. Overall, we conclude that both OA and PTX influence
      mussel phagocytic activity, and the toxic effects may depend on both the mollusc
      conditions and the activation of specific signalling pathways.

PMID- 18083047
TI  - Effects of submaximal and maximal long-lasting contractions on the compliance of
      vastus lateralis tendon and aponeurosis in vivo.
AB  - The present study investigated the effects of submaximal sustained and maximal
      repetitive contractions on the compliance of human vastus lateralis (VL) tendon
      and aponeurosis in vivo using two different fatiguing protocols. Twelve male
      subjects performed three maximum voluntary isometric contractions (MVC) of the
      knee extensors before and after two fatiguing protocols on a dynamometer. The
      first fatiguing protocol consisted of a long-lasting sustained isometric knee
      extension contraction at 25% MVC until failure (inability to hold the defined
      load). The second fatiguing protocol included long-lasting isokinetic (90
      degrees/s) knee extension contractions, where maximum moment was exerted and
      failure was proclaimed when this value fell below 70% of unfatigued maximum
      isokinetic moment. Ultrasonography was used to determine the elongation and
      strain of the VL tendon and aponeurosis. Muscle fatigue was indicated by a
      significant decrease in maximum resultant knee extension moment (p<0.05) observed
      during the MVCs after both long-lasting contractions. No significant (p>0.05)
      differences in elongation and strain of the VL tendon and aponeurosis were found,
      when compared every 300 N (tendon force) before and after the fatiguing
      protocols. The present data indicate, that the VL tendon and aponeurosis in vivo
      do not suffer from changes in the compliance neither after long-lasting static
      mechanical loading (strain approximately 3.2%) nor after long-lasting cyclic
      mechanical loading (strain 6.2-5.5%).

PMID- 18083048
TI  - Effect of sildenafil citrate (Viagra) and ethanol on the Albino rat testis: a
      scanning electron microscopic approach.
AB  - The effects of sildenafil citrate with ethanol on the rat testis was studied
      using scanning electron microscopy. Male Albino rats were divided into 8 groups,
      each being treated for a maximum of 45 days as follows. In the 4 short-term
      treatment groups, control rats were administered normal saline orally, whereas
      experimental animals were fed sildenafil citrate (Viagra) 1 microg/g with 18%
      ethanol (5 g/kg body weight), which was given orally as a single dose. After 1,
      2.5, 4 and 24h the rats were killed. In the 4 long-term treatment groups, daily
      continuous doses of drug and ethanol with a single dosage were given for 15, 30
      and 45 days and the animals killed 4h after the last dosage. Changes in the
      testis were compared with the normal healthy rat testis. The use of a scanning
      electron microscope for evaluation of the changes in the testis is more suitable
      for observation of the surface and morphological shapes of the tissue structures.

PMID- 18083049
TI  - Demarcation of the cortical division zone in dividing plant cells.
AB  - Somatic cytokinesis in higher plants involves, besides the actual construction of
      a new cell wall, also the determination of a division zone. Several proteins have
      been shown to play a part in the mechanism that somatic plant cells use to
      control the positioning of the new cell wall. Plant cells determine the division
      zone at an early stage of cell division and use a transient microtubular
      structure, the preprophase band (PPB), during this process. The PPB is formed at
      the division zone, leaving behind a mark that during cytokinesis is utilized by
      the phragmoplast to guide the expanding cell plate toward the correct cortical
      insertion site. This review discusses old and new observations with regard to
      mechanisms implicated in the orientation of cell division and determination of a
      cortical division zone.

PMID- 18083050
TI  - Effect of solvents on obligately anaerobic bacteria.
AB  - Growth of Acetobacterium woodii and Clostridium sporogenes was studied in the
      presence of water-immiscible solvents. Nitrogen purging, vacuum distillation or
      distillation under nitrogen were all suitable as methods to remove oxygen from
      the solvents, since growth rates and yields of A. woodii were unaffected in the
      presence of tetradecane which had been degassed by these methods. Varying the
      solvent volume from 20% to 80% of the culture volume had little effect on growth
      rate of A. woodii. A.woodii was relatively sensitive to organic solvents since
      growth was inhibited by alkanes with logP(octanol/water) values below 7.1. C.
      sporogenes was less solvent sensitive, since it grew without inhibition when the
      logP of the solvent was > or = 6.6. Nevertheless, both A. woodii and C.
      sporogenes were more sensitive to solvent polarity than aerobic bacteria.

PMID- 18083051
TI  - Haematological and biochemical changes in dogs naturally infected with
      Angiostrongylus vasorum before and after treatment.
AB  - Haematological and biochemical parameters were studied prospectively in 48 dogs
      naturally infected with Angiostrongylus vasorum in a primary care setting.
      Samples for analysis were obtained when treatment was started and 42days
      afterwards. Prior to treatment, 21% of affected dogs exhibited eosinophilia,
      whereas increased total white blood cell (WBC) counts and neutrophilia were
      observed in only 4.2%. WBC counts and concentrations of neutrophils, eosinophils
      and monocytes decreased significantly from days 0 to 42, indicating that, even in
      dogs without elevated absolute blood values, a low grade inflammatory response
      may be present in dogs with A. vasorum infection. Biochemical changes (especially
      an increase in serum globulins and a decrease in serum fructosamine) were in
      agreement with the findings of other studies. The results show that the diagnosis
      of canine angiostrongylosis should not be excluded based on unremarkable
      haematological and blood biochemical parameters. They also support our recent
      finding that a low serum fructosamine concentration may be associated with
      infection with A. vasorum.

PMID- 18083052
TI  - Effects of temperature on the specific dynamic action of the southern catfish,
      Silurus meridionalis.
AB  - Specific dynamic action (SDA), the energy expended on all physiological processes
      that is associated with meal digestion and assimilation, is strongly affected by
      temperature. We assessed the effects of temperature on the postprandial metabolic
      response and calculated SDA of the southern catfish, Silurus meridionalis. The
      fish was fed with experimental diets at a meal size of 4% body mass, and by using
      an 8-chamber, continuous-flow respirometer the oxygen consumption rate was
      determined at a 2 h interval until the postprandial oxygen consumption rate
      returning to the preprandial level, at four different temperatures. The energy
      expended on SDA (SDA(E)) were 2.71, 3.07, 3.16, and 3.62 kJ, the
      SDA(coefficients) (energy expended on SDA quantified as a percentage of the
      digestible energy content of the meal) were 7.70, 9.44, 10.36, and 11.12%, and
      the peak metabolic rates (R(peak)) of SDA were 3.48, 4.31, 5.96, and 7.30 mg O2
      h(-1), at 17.5, 22.5, 27.5, and 32.5 degrees C respectively. The relationships
      between those parameters and temperature were: SDA(E)=1.74+0.0559T (n=26,
      r(2)=0.676), SDA(coefficient)=4.10+0.223T (n=26, r(2)=0.726), and R(peak)=
      1.34+0.264T (n=26, r(2)=0.896). The SDA durations showed a slow-fast-slow
      tendency of decrease with increasing temperature, and were 88.00, 85.71, 67.71,
      and 66.50 h at 17.5, 22.5, 27.5 and 32.5 degrees C respectively. Two separate
      peaks appeared during the SDA response at 17.5 degrees C, and it might be due to
      a rapid startup of the mechanical process with a lag of the biochemical process,
      which suggested that the peaks of "mechanical component" and "biochemical
      component" of SDA might be separated when temperature was low enough.

PMID- 18083053
TI  - Leukotriene D(4) induces AP-1 but not NFkappaB signaling in intestinal epithelial
      cells.
AB  - We have previously shown that leukotriene D(4) (LTD(4)), a known pro-inflammatory
      mediator, induces increased survival and proliferation of intestinal epithelial
      cells. In this study we examined whether LTD(4) functions via activation of the
      transcription factors NFkappaB and AP-1, which are potent inducers of
      mitogenesis. We found that the NFkappaB inhibitory protein IkappaBalpha was not
      degraded upon LTD(4) stimulation. Furthermore, nuclear translocation of the
      classical p65 or alternative p52 subunits of NFkappaB was not observed.
      Accordingly, LTD(4) stimulation failed to induce NFkappaB transcriptional
      activity. Instead we found that LTD(4) induced phosphorylation of c-Jun-N
      terminal kinase (JNK) and transcriptional activity of AP-1, which could be
      reduced by a JNK inhibitor. Moreover, LTD(4) induced cell proliferation, and this
      effect was also blocked upon addition of a JNK inhibitor. Our findings show for
      the first time that JNK/AP-1 but not NFkappaB is a downstream target of LTD(4) in
      intestinal epithelial cells, suggesting that AP-1 is an important mediator of
      LTD(4)-induced mitogenic effects.

PMID- 18083055
TI  - Sonochemical and visible light induced photochemical and sonophotochemical
      degradation of dyes catalyzed by recoverable vanadium-containing
      polyphosphomolybdate immobilized on TiO2 nanoparticles.
AB  - Na5PV2Mo10O40 supported on nanoporous anatase TiO2 particles, TiO2-PVMo, was used
      as an efficient photocatalyst for photocatalytic degradation of different dyes by
      visible light using oxygen as oxidant. This catalyst showed a good catalytic
      activity in the sonocatalytic and sonophotocatalytic decomposition of different
      dyes in aqueous solutions. The TiO2-PVMo composite showed higher photocatalytic
      and sonocatalytic activity than pure polyoxometalate or pure TiO2.

PMID- 18083056
TI  - Functional mapping of apidaecin through secondary structure correlation.
AB  - The mechanism through which apidaecin (GNNRPVYIPQPRPPHPRL) like proline rich, non
      helical, antibacterial peptides penetrate into the bacterial cells is not yet
      clearly understood. To comprehend their transport across the bacterial cells, a
      detailed structure-activity correlation of apidaecin and its selected analogs is
      undertaken. In membrane like environment apidaecin exhibits a structural change
      which is mislaid in its biologically inactive P11-->Q substitution analog. This
      new structure, acquired by apidaecin but not by P11-->Q might be responsible for
      the difference in their antibacterial response. With this suggestion we explored
      the membrane permeation response of both by incubating them with small
      unilamellar vesicles (SUV). Unlike apidaecin, the P11-->Q did not induce leakage
      from SUV. To confirm whether this response is due to the substitution of P11-->Q
      of PQP motif, we chose P-ab (YVPLPNVPQPGRRPFPT), an N-terminal domain of abaecin
      which is homologous to apidaecin in terms of all prolines including conserved
      PQP, for comparison. Unlike P11-->Q but like apidaecin, P-ab also permeablized
      the SUV. Computational analysis also indicated that this particular mutation has
      a strong structural impact. These results led us to hypothesize that in bacterial
      environment apidaecin undergoes an ordered structural change that facilitates its
      entry into the bacterial membrane and also that PXP motives are important for
      this structural change. Apidaecin analogs not viable to organize/transform into
      this functionally active conformation are deleteriously affected. Adaptation to a
      unique conformation though insufficient (since functional binding with
      intracellular targets is also mandatory) seems to be an important prerequisite
      for the manifestation of full spectrum of antibacterial activity of apidaecin
      like peptides.

PMID- 18083054
TI  - Acetaminophen: antipyretic or hypothermic in mice? In either case, PGHS-1b (COX
      3) is irrelevant.
AB  - Acetaminophen (AC) reduces the core temperatures (T(c)) of febrile and non
      febrile mice alike. Evidence has been adduced that the selectively AC-sensitive
      PGHS isoform, PGHS-1b (COX-3), mediates these effects. PGHS-1b, however, has no
      catalytic potency in mice. To resolve this contradiction, AC was injected
      intravenously (i.v.) into conscious PGHS-1 gene-sufficient (wild-type (WT)) and 
      deficient (PGHS-1(-/-)) mice 60 min before or after pyrogen-free saline (PFS) or
      E. coli LPS (10 microg/kg) i.v. T(c) was monitored continuously; brain and plasma
      PGE(2) levels were determined hourly. AC at <160 mg/kg did not affect T(c) when
      given before PFS or LPS; at 160 mg/kg, it caused a approximately 2.5 degrees C
      T(c) fall in 60 min. LPS given after AC (all doses) induced a approximately 1
      degrees C fever, not different from that in AC-untreated mice. But this rise was
      insufficient to overcome the hypothermia of the 160 mg/kg-treated mice; their
      T(c) culminated 1 degrees C below baseline. LPS given before AC similarly
      elevated T(c) approximately 1 degrees C. This rise was reduced to baseline in 30
      min by 80 mg AC/kg; T(c) rebounded to its febrile level over the next 30 min. At
      160 mg/kg, AC reduced T(c) to 4 degrees C below baseline in 60 min, where it
      remained until the end of the experiment. WT and PGHS-1(-/-) mice responded
      similarly to all the treatments. The basal brain and plasma PGE(2) levels of PFS
      mice and the elevated plasma levels of LPS mice were unchanged by AC at 160
      mg/kg; but the latter's brain levels were reduced at 1h, then recovered. Thus, AC
      could exert an anti-PGHS-2 effect when this enzyme is upregulated in the brain of
      febrile mice. The hypothermia it induces in non-febrile mice, therefore, is due
      to another mechanism. PGHS-1b is not involved in either case.

PMID- 18083057
TI  - Nicotinic acetylcholine receptors alpha4beta2 and alpha7 regulate myelo- and
      erythropoiesis within the bone marrow.
AB  - Nicotine consumed upon smoking affects numerous physiological processes through
      nicotinic acetylcholine receptors, which mediate cholinergic regulation by the
      neuronal and endogenous acetylcholine. Consequently, nicotinic receptors are
      expressed in many non-excitable tissues including the blood. In spite of the
      documented effect of nicotine on hematopoiesis, little is known about the
      expression and role of nicotinic receptors in the course of blood cell
      differentiation. The aim of the present study was to investigate whether and how
      nicotinic receptors are involved in the development of myeloid and erythroid
      cells within the bone marrow. The presence of nicotinic receptors containing
      alpha4(beta2) and alpha7 subunits in the bone marrow cells of C57Bl/6 mice was
      shown by the binding of [125I]-alpha-bungarotoxin or [3H]-Epibatidine and by flow
      cytometry with subunit-specific antibodies or fluorescein-labeled alpha
      cobratoxin. Both TER119+ (erythroid) and CD16+CD43med (myeloid) progenitor cells
      bound more alpha4-specific antibodies than their mature forms, while the binding
      of alpha-cobratoxin and alpha7-specific antibodies was also high in mature cells.
      According to morphological analysis, either the absence of alpha7-containing
      nicotinic receptors in knockout mice or their desensitization in mice chronically
      treated with nicotine decreased the number of myeloid and erythroid progenitors
      and junior cells. In contrast, the absence of beta2-containing receptors favored
      myelocyte generation and erythroid cell maturation. It is concluded that the
      development of both myeloid and erythroid cell lineages is regulated by
      endogenous cholinergic ligands and can be affected by nicotine through alpha7-
      and alpha4beta2-containing nicotinic receptors, which play different roles in the
      course of the cell maturation.

PMID- 18083058
TI  - Functional asymmetry of the conserved cystine loops in alphabetagamma GABA A
      receptors revealed by the response to GABA activation and drug potentiation.
AB  - Ligand-gated ion channels respond to specific neurotransmitters by transiently
      opening an integral membrane ion-selective pore, allowing ions to move down their
      electrochemical gradient. A distinguishing feature of all members of the ligand
      gated ion channel superfamily is the presence of a 13-amino acid disulfide loop
      (Cys-loop) in the extracellular ligand-binding domain. Structural data derived
      from the acetylcholine receptor place this loop at the interface between the
      ligand-binding domain and the transmembrane pore-forming domain where it is
      ideally located to participate in coupling ligand binding to channel opening. We
      have introduced specific mutations into a conserved motif at the mid-point of the
      Cys-loop of the GABA A receptor subunits alpha1, beta2 and gamma2S where the
      sequence reads aromatic, proline, aliphatic (ArProAl motif). Receptors carrying a
      mutation in the Cys-loop of one of their subunits were expressed in L929 cells
      and responses to both GABA and drugs were assessed using the whole-cell patch
      clamp technique. Drug potentiation and direct activation were significantly
      enhanced by mutations in this Cys-loop but these effects were subunit-dependent.
      Currents in response to agonists were larger when mutations were carried in the
      alpha and beta subunits but not in the gamma subunit. In contrast, potentiation
      of current responses by diazepam, etomidate and pentobarbital were all enhanced
      when mutations were carried in the alpha and gamma subunits, but not the beta
      subunit. Since the disruption of interactions mediated through the ArProAl motif
      enhances the mutant receptor's response to both agonist and drugs we suggest that
      this motif in the Cys-loop of the wild-type receptor participates in interactions
      that create activation barriers to conformational changes during channel gating.

PMID- 18083059
TI  - A novel recombinantly produced banana lectin isoform is a valuable tool for
      glycoproteomics and a potent modulator of the proliferation response in CD3+,
      CD4+, and CD8+ populations of human PBMCs.
AB  - Lectins as carbohydrate-binding proteins have been employed in various biological
      assays for the detection and characterization of glycan structures on
      glycoproteins, including clinical biomarkers in disease states. A mannose
      specific banana lectin (BanLec) is unique in its specificity for internal
      alpha1,3 linkages as well as beta1,3 linkages at the reducing termini. The
      immunomodulatory potential of natural BanLec was recognized by a strong
      immunoglobulin G4 antibody response and T cell mitogen activity in humans. To
      explore its applicability in glycoproteomics and its modulatory potential, the
      gene of banana lectin was cloned, sequenced and a recombinant protein was
      produced in Escherichia coli. The obtained cDNA revealed a novel banana lectin
      isoform, with an open reading frame of 426 nucleotides, encoding a cytoplasmatic
      protein of 141 amino acids. The molecular mass of rBanLec determined by ESI FT-MS
      and N-terminal sequencing confirmed the cDNA at the protein level. The
      specificity of rBanLec for detection glycan structures was the same as for
      natural BanLec as examined with five protein extracts rich in glycoprotein
      content, as well as with horseradish peroxidase glycoprotein. Besides, the
      immunomodulatory potential of rBanLec and nBanLec were comparable as assessed by
      an inhibition assay and a human T cell proliferation assay where they induced a
      strong proliferation response in CD3+, CD4+, and CD8+ populations of human PBMCs.
      This recombinant BanLec is a useful reagent for glycoproteomics and lectin
      microarrays, with a potential for modulation of the immune response.

PMID- 18083060
TI  - Inflammatory cytokines and dendritic cells in acute graft-versus-host disease
      after allogeneic stem cell transplantation.
AB  - The wider use of allogeneic stem cell transplantation (allo-SCT) is still limited
      by the immunologic recognition and destruction of host tissues, termed graft
      versus-host disease (GVHD). The role of inflammatory cytokines such as TNF-alpha
      and IL-1, and their impact on immune effectors (mainly CD4+ and CD8+ T) cells has
      been extensively studied in the context of GVHD occurring after standard
      myeloablative allo-SCT. However, recent data suggested that GVHD pathophysiology
      is likely to involve more complex interactions where antigen-presenting cells,
      especially dendritic cells (DCs), may play a major role at time of initiation of
      acute GVHD. In addition, the wider use of reduced intensity and less toxic
      conditioning (RIC) regimens prior to allo-SCT would allow better visualization of
      the fine functions of immune effectors, thereby offering a window of
      opportunities to better decipher the intimate pathophysiological mechanisms
      underlying GVHD. The aim of this work is to review the available research
      evidence on the role of DCs as in vivo regulators of alloimmune reactivity, and
      their interactions with other immune effectors.

PMID- 18083061
TI  - Folate biofortification in food plants.
AB  - Folate deficiency is a global health problem affecting many people in the
      developing and developed world. Current interventions (industrial food
      fortification and supplementation by folic acid pills) are effective if they can
      be used but might not be possible in less developed countries. Recent advances
      demonstrate that folate biofortification of food crops is now a feasible
      complementary strategy to fight folate deficiency worldwide. The genes and
      enzymes of folate synthesis are sufficiently understood to enable metabolic
      engineering of the pathway, and results from pilot engineering studies in plants
      (and bacteria) are encouraging. Here, we review the current status of
      investigations in the field of folate enhancement on the eve of a new era in food
      fortification.

PMID- 18083062
TI  - Impact of the comet assay in radiobiology.
AB  - Until the development of single cell gel electrophoresis methods in the 1980s,
      measurement of radiation-induced DNA strand breaks in individual cells was
      limited to detection of micronuclei or chromosome breaks that measured the
      combined effects of exposure and repair. Development of methods to measure the
      extent of migration of DNA from single cells permitted detection of initial
      radiation-induced DNA breaks present in each cell. As cells need not be
      radiolabeled, there were new opportunities for analysis of radiation effects on
      cells from virtually any tissue, provided a single cell suspension could be
      prepared. The comet assay (as this method was subsequently named) was able to
      measure, for the first time, the fraction of radiobiologically hypoxic cells in
      mouse and human tumors. It was used to determine that the rate of rejoining of
      DNA breaks was relatively homogenous within an irradiated population of cells.
      Because individual cells were analyzed, heavily damaged or apoptotic cells could
      be identified and eliminated from analysis to determine "true" DNA strand break
      rejoining rates. Other examples of applications of the comet assay in
      radiobiology research include analysis of the inter-individual differences in
      response to radiation, effect of hypoxia modifying agents on tumor hypoxic
      fraction, the role of cell cycle position during DNA break induction and
      rejoining, non-targeted effects on bystander cells, and effects of charged
      particles on DNA fragmentation patterns.

PMID- 18083063
TI  - Spectral features of substituted 9-(phenoxycarbonyl)-acridines and their
      protonated and methylated cation derivatives.
AB  - The long-wavelength absorption of eight 9-(phenoxycarbonyl)-acridines and the 10
      H-9-(phenoxycarbonyl)-acridinium and 10-methyl-9-(phenoxycarbonyl)-acridinium
      cations derived from them, substituted with an alkyl or trifluoroalkyl group at
      the benzene ring, occurs above 300 nm as the superposition of four bands. Three
      of these bands occupy comparable positions (expressed in nm) in all the
      compounds; the fourth one, however, changes position, appearing in neutral
      molecules as a long-wavelength shoulder below 400 nm, but in cations as an almost
      separate band above 400 nm. The weak fluorescence resulting from excitation
      within the long-wavelength absorption band is red-shifted relative to absorption,
      such that Stokes shifts are similar for both neutral molecules and cations.
      Stokes shifts tend to increase with the orientational polarisability of a medium.
      Computations predict that long-wavelength electronic transitions are accompanied
      by structural changes in molecules. They also indicate that such transitions are
      followed by roughly uniform electron density changes in whole molecules
      accompanied by small changes in their dipole moments, which accounts for the weak
      absorption in the long-wavelength region. The predicted radiative and non
      radiative deactivation rate constants suggest the occurrence of efficient spin
      orbital coupling in the molecules investigated, which is the cause of the
      relatively low fluorescence quantum yields. Apart from the cognitive significance
      of these investigations, the results demonstrate that absorption of radiation by
      10-methyl-9-(phenoxycarbonyl)-acridinium cations above 400 nm may influence their
      chemiluminescence output.

PMID- 18083064
TI  - Relationships between swim performance, maximal oxygen uptake and peak power
      output when wearing a wetsuit.
AB  - This study was intended to investigate the effect of wearing a wetsuit (WS) on
      physical performance capacity, which are maximal oxygen uptake (V O(2)max) and
      maximal mechanical power output (POmax), and to demonstrate whether wearing a WS
      affected the relationship between maximal 400m swim performance (V400) and V
      O(2)max, and between sprint swim performance (Vsprint) and V O(2)max. Twelve
      triathletes participated in this study. V O(2)max was determined during the
      continuous progressive swimming test. The mean velocity over maximal 400m swim
      was defined as V400. Active drag (AD), Vsprint and POmax were measured by a
      specific method called "perturbation method". Compared with wearing a swimsuit
      (SS), V400 was improved without enhancing V O(2)max and Vsprint was also improved
      without enhancing POmax and AD by wearing a WS. Significant correlations were
      found between V400 and V O(2)max and between Vsprint and POmax in the both suit
      conditions, but a higher correlation was found in the WS condition than in the SS
      condition. These results suggested that improved swim performance from wearing a
      WS was attributable only to improvement in technical factors, such as propulsion
      efficiency. In conclusion, during swimming with a WS, performance gain was not
      associated with physiological factors but with propulsion efficiency related to a
      gain in buoyancy and to drag reduction. However, when wearing a WS, V400 and
      Vsprint more reflected the values of V O(2)max and POmax, respectively.

PMID- 18083065
TI  - Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status
      for postmenopausal women with endocrine-responsive early breast cancer:
      supplementary results from the BIG 1-98 randomised trial.
AB  - BACKGROUND: The Breast International Group (BIG) 1-98 trial (a randomised double
      blind phase III trial) has shown that letrozole significantly improves disease
      free survival (DFS) compared with tamoxifen in postmenopausal women with
      endocrine-responsive early breast cancer. Our aim was to establish whether the
      benefit of letrozole versus tamoxifen differs according to the ERBB2 status of
      tumours. METHODS: The BIG 1-98 trial consists of four treatment groups that
      compare 5 years of monotherapy with letrozole or tamoxifen, and sequential
      administration of one drug for 2 years followed by the other drug for 3 years.
      Our study includes data from the 4922 patients randomly assigned to the two
      monotherapy treatment groups (letrozole or tamoxifen for 5 years; 51 months
      median follow-up [range <1 to 90 months]). A central assessment of oestrogen
      receptor (ER), progesterone receptor (PgR) and ERBB2 status using paraffin
      embedded primary tumour material was possible for 3650 (74%) patients. ER, PgR,
      and ERBB2 expression were measured by immunohistochemistry (IHC) and ERBB2
      positivity was confirmed by fluorescence in-situ hybridisation (FISH). Positive
      staining in at least 1% of cells was considered to show presence of ER or PgR
      expression. Tumours were deemed ERBB2-positive if amplified by FISH, or, for the
      few tumours with unassessable or unavailable FISH results, if they were IHC 3+.
      Hazard ratios (HR) estimated by Cox modelling were used to compare letrozole with
      tamoxifen for DFS, which was the primary endpoint, and to assess treatment-by
      covariate interactions. The BIG 1-98 trial is registered on the clinical trials
      site of the US National Cancer Institute website
      http://www.clinicaltrials.gov/ct/show/NCT00004205. FINDINGS: By central
      assessment 7% (257 of 3650) of tumours were classified as ERBB2-positive. In 3533
      patients with tumours confirmed to express ER, DFS was poorer in patients with
      ERBB2-positive tumours (n=239) than in those with ERBB2-negative tumours (n=3294;
      HR 2.09 [95% CI 1.59-2.76]; p<0.0001). There was no statistical evidence of
      heterogeneity in the treatment effect according to ERBB2 status of the tumour
      (p=0.60 for interaction), thus, letrozole improves DFS compared with tamoxifen
      regardless of ERBB2 status. The observed HRs were 0.62 (95% CI 0.37-1.03) for
      ERBB2-positive tumours and 0.72 (0.59-0.87) for ERBB2-negative tumours.
      INTERPRETATION: A benefit of letrozole over tamoxifen was noted, irrespective of
      ERBB2 status of the tumour, and, therefore, ERBB2 status does not seem to be a
      selection criterion for treatment with letrozole versus tamoxifen in
      postmenopausal women with endocrine-responsive early breast cancer.

PMID- 18083066
TI  - Organizing the fluid membrane bilayer: diseases linked to spectrin and ankyrin.
AB  - Ankyrin and spectrin were first discovered as binding partners in the membrane
      skeleton of human erythrocytes. Mutations in genes encoding these proteins cause
      hereditary spherocytosis. Recent advances reveal that ankyrin and spectrin are
      required for organization of a surprisingly diverse set of proteins, including
      ion channels and cell adhesion molecules that are localized in specialized
      membrane domains in many cell types. New insights into the cell biology of
      ankyrin and spectrin reveal that these proteins actively participate in assembly
      of specialized membrane domains in addition to their conventional maintenance
      role as scaffolding proteins. Recently described inherited human diseases due to
      defects in spectrin or ankyrin include spinocerebellar ataxia type 5 and a
      cardiac arrhythmia, termed sick sinus syndrome with bradycardia or ankyrin-B
      syndrome. Together, these studies identify an emerging paradigm for pathogenesis
      of human disease where failure in cellular localization of membrane-spanning
      proteins results in loss of physiological function.

PMID- 18083067
TI  - Development and evaluation of a gamma-interferon assay for tuberculosis in
      badgers (Meles meles).
AB  - In this paper we report the development of a sensitive and specific assay for the
      detection of tuberculosis (TB) in European badgers (Meles meles), based on the
      stimulation of lymphocytes in whole-blood culture and the subsequent detection of
      gamma-interferon (IFNgamma) by sandwich ELISA. The comparative levels of IFNgamma
      produced to bovine and avian tuberculin (B-A) was used as the basis of
      determining the TB status of badgers, resulting in a more sensitive test than
      that based on the defined Mycobacterium bovis antigens ESAT6 and CFP10. The assay
      was evaluated using 235 badgers. The IFNgamma EIA (enzyme immunoassay) based on a
      monoclonal pair (mEIA) was more sensitive than one using a rabbit polyclonal
      antiserum (pEIA). At a specificity of 93.6%, the mEIA was 80.9% sensitive,
      compared to a sensitivity of 74.5% for the pEIA. At the same specificity as the
      EIA, the current serological ELISA test for TB in badgers (Brock test) had a
      sensitivity of 48.9%. Only one of the culture positive badgers missed by the mEIA
      was correctly diagnosed by the Brock test, suggesting that the combination of
      both a T-cell and serological test has little diagnostic advantage.

PMID- 18083068
TI  - Lycopus lucidus inhibits high glucose-induced vascular inflammation in human
      umbilical vein endothelial cells.
AB  - Vascular inflammatory process has been suggested to play a key role in the
      initiation and progression of atherosclerosis, a major complication of diabetes
      mellitus. Lycopus lucidus Turcz. has been used as an oriental traditional
      medicine including Korea and its crude drug is known to have an anti-inflammatory
      effect. Thus we investigated whether the aqueous extract of the leaves of L.
      lucidus Turcz. (ALT) suppresses vascular inflammatory process induced by high
      glucose in primary cultured human umbilical vein endothelial cells (HUVEC).
      Western blot analysis revealed that incubation of HUVEC with high glucose
      increased cell adhesion molecules (CAMs) expression levels. However, high glucose
      induced increase of CAMs expression was significantly attenuated by pretreatment
      with ALT in a dose-dependent manner. The enhanced cell adhesion between monocyte
      and HUVEC induced by high glucose was also blocked by pretreatment with ALT. High
      glucose-induced hydrogen peroxide production and DCF-sensitive intracellular
      reactive oxygen species (ROS) formation. Pretreatment with ALT inhibited high
      glucose-induced ROS formation. In addition, ALT suppressed the translocation and
      promoter transcriptional activity of NF-kappaB increased in high glucose
      condition. Taken together, the present data suggested that ALT could suppress
      high glucose-induced vascular inflammatory process, which may be closely related
      with the inhibition of ROS and NF-kappaB activation in HUVEC.

PMID- 18083069
TI  - Barium esophagography: a study for all seasons.
AB  - Although a variety of diagnostic procedures are often performed on patients with
      pharyngeal or esophageal symptoms, barium esophagography is a noninvasive,
      inexpensive, and readily available test that can simultaneously evaluate
      swallowing function, esophageal motility, gastroesophageal reflux, and a host of
      structural abnormalities in the pharynx and esophagus. This article reviews the
      role of barium esophagography for assessing swallowing function, morphologic
      abnormalities of the pharynx (diverticula, webs, and carcinoma), esophageal
      motility disorders (achalasia and diffuse esophageal spasm), and morphologic
      abnormalities of the esophagus (reflux esophagitis, Barrett's esophagus,
      infectious esophagitis, drug-induced esophagitis, eosinophilic esophagitis,
      Schatzki's ring, and esophageal carcinoma).

PMID- 18083070
TI  - Sympathetic neural activity and the pathogenesis of sudden cardiac death.

PMID- 18083071
TI  - Genome-wide demethylation promotes triplet repeat instability independently of
      homologous recombination.
AB  - Trinucleotide repeat instability is intrinsic to a family of human
      neurodegenerative diseases. The mechanism leading to repeat length variation is
      unclear. We previously showed that treatment with the demethylating agent 5-aza
      2'-deoxycytidine (5-aza-CdR) dramatically increases triplet repeat instability in
      mammalian cells. Based on previous reports that demethylation increases
      homologous recombination (HR), and our own observations that HR destabilizes
      triplet repeats, we hypothesized that demethylation alters repeat stability by
      stimulating HR. Here, we test that hypothesis at the adenosine phosphoribosyl
      transferase (Aprt) locus in CHO cells, where CpG demethylation and HR have both
      been shown to increase CAG repeat instability. We find that the rate of HR at the
      Aprt locus is not altered by demethylation. The spectrum of recombinants,
      however, was shifted from the usual 6:1 ratio of conversions to crossovers to
      more equal proportions in 5-aza-CdR-treated cells. The subtle influences of
      demethylation on HR at the Aprt locus are not sufficient to account for its
      dramatic effects on repeat instability. We conclude that 5-aza-CdR promotes
      triplet repeat instability independently of HR.

PMID- 18083074
TI  - A rapid and validated HPLC method to quantify racecadotril metabolite, thiorphan,
      in human plasma using solid-phase extraction.
AB  - A HPLC method with UV detection was developed and validated for the determination
      of thiorphan in human plasma. Nevirapine was used as the internal standard.
      Separation was performed by a Waters sunfire C18 reversed-phase column maintained
      at 35 degrees C. The mobile phase was a mixture of 0.05 M phosphate buffer with
      the pH adjusted to 2.6 and acetonitrile (74:26, v/v) at a flow rate of 1.0
      mL/min. The UV detector was set at 210 nm. An original pre-treatment of plasma
      samples was developed, based on solid-phase extraction (SPE) with solid-phase
      extraction cartridges (Oasis HLB 3 mL, 60 mg). The extraction recovery for plasma
      samples of thiorphan at 0.1, 0.4 and 2.0 microg/mL was 93.5%, 98.2% and 97.8%,
      respectively. The calibration curve was linear with the correlation coefficient
      (r) above 0.9998. Linearity was verified over the range of 0.05-4 microg/mL
      thiorphan in plasma. The limit of quantification (LOQ) is 0.05 microg/mL. The
      mean accuracy was 92.7-99.6%. The coefficient of variation (precision) in the
      within- and between-batch was 2.2-8.4% and 4.1-8.1%, respectively. This method is
      simple, economical and specific, and has been used successfully in a
      pharmacokinetic study of thiorphan.

PMID- 18083072
TI  - Thiophilic-interaction chromatography of enzymatically active tissue prostate
      specific antigen (T-PSA) and its modulation by zinc ions.
AB  - Prostate-specific antigen (PSA) is a serine protease secreted both by normal
      prostate glandular epithelial cells and prostate cancer cells. We explored
      "thiophilic-interaction chromatography" (TIC) to isolate tissue prostate-specific
      antigen (T-PSA) from fresh human prostate cancer tissue harvested by radical
      prostatectomy for the purpose to characterize T-PSA for its enzymatic activity
      and sensitivity to zinc ions. We have shown, for the first time, that T-PSA has
      strong affinity for the thiophilic gel (T-gel). The average recovery of T-PSA
      from T-gel is over 87%. The presence of PSA in the column eluate was confirmed by
      ELISA and SDS/PAGE. Western blot developed with monoclonal antibody to PSA
      revealed that T-PSA was predominantly in the "free" form having a molecular
      weight of 33 kDa. Furthermore, T-PSA was found to be enzymatically active. T-PSA
      was found to be less enzymatically active as compared to seminal plasma PSA. The
      inhibition of enzymatic activity of both f-PSA and T-PSA over a wide range of
      concentrations of Zn(2+) ions (10nM to 50 microM) was comparable. In contrast,
      the enzymatic activity of chymotrypsin, another serine-protease, was affected
      differently. At higher concentrations of Zn(2+) (10 microM and higher) the
      enzymatic activity of chymotrypsin was inhibited, whereas, at lower
      concentrations of Zn(2+) (5 microM and lower), the enzymatic activity was
      enhanced.

PMID- 18083075
TI  - Quantification of cidofovir in human serum by LC-MS/MS for children.
AB  - A new method for the quantification of cidofovir (CDV), an acyclic nucleotide
      analogue of cytosine with antiviral activity against a broad-spectrum of DNA
      viruses, in human serum, using high-performance liquid chromatography coupled to
      tandem mass spectrometry (LC-MS/MS) has been developed. A strong anion exchange
      (SAX) solid-phase extraction procedure was applied for the sample preparation.
      The tandem mass spectrometer was tuned in the multiple reaction monitoring mode
      to monitor the m/z 278.1-->234.9 and the m/z 288.1-->133.1 transitions for CDV
      and the internal standard 9-(2-phosphonylmethoxyethyl)guanine (PMEG),
      respectively, using negative electrospray ionization. The MS/MS response was
      linear over the concentration range from 78.125 ng/ml to 10,000 ng/ml, with a
      lower limit of quantification of 78.125 ng/ml. The intra- and inter-day
      precisions (relative standard deviation (%)) for CDV were less than 7.8% and the
      accuracies (% of deviation from nominal level) were within +/-12.1% for quality
      controls. The novel LC-MS/MS method allowed a specific, sensitive and reliable
      determination of CDV in human serum and was applied to investigate the yet
      unknown pharmacokinetic properties of CDV in a paediatric cancer patient.

PMID- 18083076
TI  - Removal of a large stone growing around and encasing a plastic biliary stent:
      respect the ductal axis.
AB  - Plastic biliary stents are commonly used during Endoscopic Retrograde Cholangio
      Pancreatography (ERCP). The main indication for biliary stenting is benign or
      malignant obstruction. Plastic stents, among others, can be used as an escape
      route in patients with large common bile duct stones, or in cases of acute
      cholangitis with or without sphincterotomy to provide drainage until definitive
      treatment. Stent occlusion is the main disadvantage, limiting their patency to
      around 3 months, after which replacement is recommended. We present a case of a
      large, close to 2cm, stone developing around and encasing the proximal end of a
      plastic biliary stent. The stent/stone complex was successfully removed en bloc.
      The stent was placed in the common bile duct without sphincterotomy, and remained
      in situ for 2 years. The presented case highlights the importance of definitive
      treatment for common bile duct stones, the need to respect the ductal axis
      especially when dealing with large stones and the significance of biliary
      sphincterotomy during endoscopic interventions in the bile duct.

PMID- 18083077
TI  - A case of recurrent pyogenic cholangitis.

PMID- 18083078
TI  - Catastrophic gastrointestinal manifestations of post-transplant
      lymphoproliferative disorder.
AB  - Post-transplant lymphoproliferative disorder is a rare complication after bone
      marrow transplantation and frequently involves gastrointestinal tract, but the
      endoscopic characteristics and catastrophic clinical manifestations in adults
      have not been discussed in detail. We report a 35-year-old allogeneic bone marrow
      transplantation recipient who presented with recurrent gastrointestinal bleeding.
      Ulcerative nodular lesions were noted in stomach, duodenum and ileum on endoscopy
      but were not biopsied because of thrombocytopenia. Obstruction and perforation of
      small intestine occurred 5 months after bone marrow transplantation and was
      managed with surgery. Histopathology revealed the diagnosis of Epstein-Barr virus
      related post-transplant lymphoproliferative disorder. Rituximab was given after
      operation but repeated intestinal perforation supervened and resulted in
      mortality. The characteristic endoscopic and radiographic features are presented.
      Recognition of these characteristic endoscopic and radiographic findings with
      histological confirmation is crucial in making early diagnosis, and prompt
      treatment may prevent gastrointestinal complications and mortality.

PMID- 18083079
TI  - Absence of nodular regenerative hyperplasia after low-dose 6-thioguanine
      maintenance therapy in inflammatory bowel disease patients.
AB  - BACKGROUND: The use of 6-thioguanine has been proposed as a rescue drug for
      inflammatory bowel disease patients. Initial data on short-term efficacy and
      toxicity of 6-thioguanine were promising; however, these have been challenged by
      reports concerning its potential hepatotoxic effect (nodular regenerative
      hyperplasia). We proposed that these histological liver abnormalities may well be
      dose- or level-dependent. AIMS: We performed a prospective multi-centre study on
      the hepatotoxic potential of long-term and (as compared with prior studies) low
      dose 6-thioguanine use. PATIENTS: Inflammatory bowel disease patients using 6
      thioguanine for at least 30 consecutive months and consenting to undergo a liver
      biopsy were enrolled. METHODS: Liver biopsy specimens were scored by two
      pathologists, unaware of clinical data. Laboratory parameters, determined prior
      to initiation of 6-thioguanine therapy and prior to biopsy, were reviewed.
      RESULTS: Twenty-eight biopsies were analysed. The majority of patients (89%) were
      azathioprine and/or 6-mercaptopurine intolerant inflammatory bowel disease
      patients. In 26 patients (93%) no signs of nodular regenerative hyperplasia were
      detected; in two additional patients nodular regenerative hyperplasia could not
      be excluded due to inconclusive pathological findings. The mean 6-thioguanine
      dosage, 6-thioguaninenucleotides level, duration of use and cumulative dosage
      were 19.5mg, 564 pmol/8 x 10(8) RBC, 38 months and 22491 mg, respectively.
      CONCLUSIONS: We have demonstrated that low-dose 6-thioguanine maintenance therapy
      in inflammatory bowel disease patients is not likely to be associated with
      induction of nodular regenerative hyperplasia. The induction of nodular
      regenerative hyperplasia appears to be 6-thioguanine dose or 6
      thioguaninenucleotides level dependent.

PMID- 18083080
TI  - Fixation of a covered self-expandable metal stent by means of a polypectomy
      snare: an easy method to prevent stent migration.
AB  - Management of oesophageal leaks is controversial. Covered self-expandable
      metallic stents have been used for several conditions, but migration of the
      stents is frequent. We report the case of a patient with post-surgery oesophageal
      fistula in which, to prevent dislocation, a covered self-expandable-metallic
      stent was fixed externally using a polypectomy snare.

PMID- 18083081
TI  - Increasing hepatitis B vaccination coverage among healthcare workers in Italy 10
      years apart.
AB  - BACKGROUND: In Italy, vaccination against hepatitis B virus infection was
      strongly recommended for healthcare workers since 1985. Update findings on
      vaccination coverage are lacking. AIM: To assess current vaccination coverage
      against hepatitis B in this job category. METHODS: In 2006, 1,632 healthcare
      workers randomly selected in 15 Italian public hospitals completed a self
      administered precoded questionnaire. RESULTS: The overall vaccination coverage
      was 85.3%, a figure higher than the 64.5% observed in 1996. Vaccine coverage
      showed a significant downtrend (p<0.01) from the Northern (93.1%) to the Southern
      (77.7%) areas. Logistic regression analysis showed that residence in the North
      (Odds ratio 4.2; 95% confidence interval 2.6-6.7) and youngest age (Odds ratio
      4.5; 95% confidence interval 2.6-7.8), both were independent predictors of
      vaccine acceptance. CONCLUSIONS: Ten years apart, vaccine coverage has markedly
      increased, closely paralleling the downtrend in the incidence of acute B
      hepatitis among healthcare workers in Italy.

PMID- 18083082
TI  - Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large
      cohort of Italian women with intrahepatic cholestasis of pregnancy.
AB  - BACKGROUND: Intrahepatic cholestasis of pregnancy is a multifactorial disorder of
      pregnancy associated with a genetic background. AIM: To evaluate the genetic
      contribution of ABCB4, MDR3 gene in the development of intrahepatic cholestasis
      of pregnancy in a large cohort of Italian subjects. METHODS: This study
      represents an extension of a previous multicentre-prospective study including
      three Italian referral centres. In all, we enrolled 96 women at the 3rd trimester
      of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes
      by standard procedures. Polymerase chain reaction was used to amplify exon 14, 15
      and 16 of MDR3 gene. RESULTS: We found 3 non-synonymous heterozygous mutations in
      exon 14 (E528D, R549H, G536A), 1 in exon 15 (R590Q) and 2 in exon 16 (R652G,
      T6671). MDR3 gene variants in exons 14, 15 and 16 occurred in 7/96 of pregnant
      mothers with intrahepatic cholestasis of pregnancy (7.2%), and in none of 96
      pregnant controls matched for age and parity. All seven patients had normal gamma
      glutamyl transpeptidase, normal bilirubin, but high levels of both alanine
      transferase and serum bile acids. One had cholesterol biliary lithiasis. The
      outcome of pregnancy was normal in four cases (with vaginal delivery), while
      there was one fetal distress. CONCLUSIONS: MDR3 mutations are responsible for the
      development of intrahepatic cholestasis of pregnancy in only a small percentage
      of Italian women. Further genetic studies are warranted, however, to clarify the
      role of different mutations in intrahepatic cholestasis of pregnancy.

PMID- 18083083
TI  - Noninvasive assessment of liver fibrosis by measurement of stiffness in patients
      with nonalcoholic fatty liver disease (NAFLD).
AB  - BACKGROUND: Liver fibrosis is the main predictor of the progression of
      nonalcoholic fatty liver disease. Transient elastography (FibroScan), which
      measures liver stiffness, is a novel, noninvasive method to assess liver
      fibrosis. AIM: We investigated the usefulness of liver stiffness measurement in
      the evaluation of liver fibrosis in nonalcoholic fatty liver disease patients.
      STUDY POPULATION: A total of 97 nonalcoholic fatty liver disease patients.
      METHODS: Transient elastography was performed for liver stiffness measurement in
      97 nonalcoholic fatty liver disease patients. And the relationship between
      histological parameters and liver stiffness measurement was studied by
      multivariate analysis. Moreover, we investigated the relationship between liver
      stiffness measurement and the serum levels of hyaluronic acid and type IV
      collagen 7s domain. RESULTS: The liver stiffness was well correlated with the
      stage of liver fibrosis (Kruskal-Wallis test p < 0.0001). The areas under the
      receiver-operating characteristic curves were 0.927 for > or = F1, 0.865 for > or
      = F2, 0.904 for > or = F3, 0.991 for > or = F4. Only fibrosis stage was
      correlated significantly with liver stiffness measurement by multiple regression
      analysis. Liver stiffness was also strongly correlated with the serum levels of
      type IV collagen 7s domain (r = 0.525, p < 0.0001) and hyaluronic acid (r =
      0.457, p < 0.0001). CONCLUSIONS: Our results show a significant correlation
      between liver stiffness measurement and fibrosis stage in nonalcoholic fatty
      liver disease patients, as confirmed by the results of liver biopsy, which
      remains the gold standard for evaluation of the severity of liver fibrosis in
      patients with nonalcoholic steatohepatitis.

PMID- 18083084
TI  - DNA of Helicobacter spp. and common gut bacteria in primary liver carcinoma.
AB  - BACKGROUND AND AIM: Gastric and enteric Helicobacter species have been associated
      with the pathogenesis of some extragastric diseases. METHODS: We retrospectively
      investigated the presence of DNA of Helicobacter species in samples of the cancer
      and the surrounding tumour-free liver tissues of patients with hepatocellular
      carcinoma (HCC, n=12) and cholangiocarcinoma (CC, n=13). The patients were from
      an area with low liver cancer incidence and with low hepatitis B and C
      prevalence. Patients with a benign liver disease (n=24) were included as
      controls. Paraffin-embedded liver samples were examined by a Helicobacter genus
      specific PCR assay as well as group-specific PCR assays for Enterobacteriaceae,
      Bacteroides, Lactobacillus and Enterococcus. PCR products of positive samples
      were characterised by denaturing gradient gel electrophoresis (DGGE) and DNA
      sequencing. RESULTS: PCR assay detected Helicobacter DNA in seven of 12 (58%) and
      eight of 13 (62%) normal liver tissue specimens from HCC and CC patients,
      respectively. Two cancer samples from HCC patients were Helicobacter-positive but
      none of the CC cancers. In the control group, three of 24 (12.5%) patients with a
      benign liver condition were positive for Helicobacter species (p<0.01 compared to
      results of tumour-free liver tissue from the cancer patients). DGGE and DNA
      sequence analysis showed that 90% of the detected PCR products were "H. pylori
      like". DNA of some other enteric bacteria was detected in the liver of one cancer
      patient and one control (4% of all patients). CONCLUSION: The presence of DNA of
      Helicobacter species in liver specimens, but not of other common gut bacteria,
      was associated with human hepatic carcinogenesis.

PMID- 18083085
TI  - Serologic screening for coeliac disease in risk groups: is once in the lifetime
      enough?

PMID- 18083086
TI  - Discussion of 'Transverse thoracodorsal artery perforator flaps: experience with
      31 free flaps'.

PMID- 18083087
TI  - [The outcome of the living donor].
AB  - There is no zero risk of morbi-mortality for the donor in the procedure of living
      donation of a kidney but according to the literature, this risk is extremely low.
      Mortality in the per- et peri-operative period is estimated to be 0.03% and
      severe postoperative complications, requiring or not surgery, between 0.3 and 1%.
      The long-term mortality of these donors, selected for their good health, is
      better than that of the general population paired for age. Renal function after
      donation is around 75% the predonation and declines with age as and no more than
      in every person with two kidneys. Although significant proteinuria (>1gr/l) in 3%
      of the donors and cases of end stage renal disease have been reported, the renal
      risk remains low. Among the parameters of follow-up, a special consideration has
      to be made for blood pressure as it will significantly increase after nephrectomy
      with a possible risk of developing hypertension in predisposed persons.

PMID- 18083088
TI  - Comparing two survey methods for estimating maternal and perinatal mortality in
      rural Cambodia.
AB  - PURPOSE: We need solid estimates of maternal mortality rates (MMR) to monitor the
      impact of maternal care programs. Cambodian health authorities and WHO report the
      MMR in Cambodia at 450 per 100,000 live births. The figure is drawn from surveys
      where information is obtained by interviewing respondents about the survival of
      all their adult sisters (sisterhood method). The estimate is statistically
      imprecise, 95% confidence intervals ranging from 260 to 620/100,000. The MMR
      estimate is also uncertain due to under-reporting; where 80-90% of women deliver
      at home maternal fatalities may go undetected especially where mortality is
      highest, in remote rural areas. The aim of this study was to attain more reliable
      MMR estimates by using survey methods other than the sisterhood method prior to
      an intervention targeting obstetric rural emergencies. PROCEDURES: The study was
      carried out in rural Northwestern Cambodia where access to health services is
      poor and poverty, endemic diseases, and land mines are endemic. Two survey
      methods were applied in two separate sectors: a community-based survey gathering
      data from public sources and a household survey gathering data direct from
      primary sources. FINDINGS: There was no statistically significant difference
      between the two survey results for maternal deaths, both types of survey reported
      mortality rates around the public figure. The household survey reported a
      significantly higher perinatal mortality rate as compared to the community-based
      survey, 8.6% versus 5.0%. Also the household survey gave qualitative data
      important for a better understanding of the many problems faced by mothers giving
      birth in the remote villages. There are detection failures in both surveys; the
      failure rate may be as high as 30-40%. PRINCIPLE CONCLUSION: Both survey methods
      are inaccurate, therefore inappropriate for evaluation of short-term changes of
      mortality rates. Surveys based on primary informants yield qualitative
      information about mothers' hardships important for the design of future maternal
      care interventions.

PMID- 18083089
TI  - Gene targeting in embryonic stem cells scores a knockout in Stockholm.
AB  - The 2007 Nobel Prize in Physiology or Medicine has been awarded to Mario
      Capecchi, Martin Evans, and Oliver Smithies for developing specific gene
      modification techniques and mouse embryonic stem cell technology that, when
      combined, enable the creation of "knockout" mice. Analyses of these mutant
      animals have revolutionized the elucidation of gene functions, and these mice
      have proved to be valuable models of numerous human diseases.

PMID- 18083090
TI  - Autophagy and cell death: no longer at odds.
AB  - Autophagy has been associated with both cell survival and cell death, but the
      role of autophagy in cell death has been controversial. In this issue, Berry and
      Baehrecke (2007) report that autophagy is involved in physiological cell death
      during Drosophila development and is controlled by similar mechanisms as those
      that control its function in cell survival.

PMID- 18083091
TI  - Synapse remodeling, compliments of the complement system.
AB  - A growing body of evidence indicates that some proteins known for their immune
      functions also have distinct nonimmune functions in the normal uninjured central
      nervous system. In this issue, Stevens et al. (2007) demonstrate an unexpected
      requirement for molecules of the complement cascade in the remodeling of synaptic
      connections in the developing visual system.

PMID- 18083092
TI  - The exoneme helps malaria parasites to break out of blood cells.
AB  - Malaria parasites must invade the erythrocytes of its host, to be able to grow
      and multiply. Having depleted the host cell of its nutrients, the parasites break
      out to invade new erythrocytes. In this issue of Cell, Yeoh et al. (2007)
      discover a new organelle, the exoneme, that contains a protease SUB1, which helps
      the parasite to escape from old erythrocytes and invade new ones.

PMID- 18083093
TI  - TAMpering with toll-like receptor signaling.
AB  - Toll-like receptors (TLRs) provoke a profound inflammatory response during host
      defense and must be controlled in order to avoid autoimmune and inflammatory
      diseases. In this issue, Rothlin et al. (2007) uncover a complex negative
      feedback mechanism to limit TLR signaling involving the Tyro3/Axl/Mer (TAM)
      family of receptor tyrosine kinases, which induce expression of the inhibitory
      proteins SOCS1 and SOCS3.

PMID- 18083094
TI  - Sticklebacks and humans walk hand in fin to lighter skin.
AB  - In this issue, Miller et al. (2007) show that evolution makes repeated use of the
      same genes to produce light pigmentation in animals as divergent as stickleback
      fish and humans. This study indicates that analyzing parallel evolution at the
      genetic level could help to answer a number of outstanding questions in
      evolutionary genetics.

PMID- 18083095
TI  - A seminal finding for understanding HIV transmission.
AB  - Although the worldwide incidence of HIV infection is high, the retrovirus
      displays a surprisingly low infectivity in vitro. As a potential explanation for
      this discrepancy, Munch et al. (2007) now identify and characterize a factor
      found in human semen that under certain conditions can enhance HIV infectivity by
      more than 100,000-fold.

PMID- 18083096
TI  - Calcium signaling.
AB  - Calcium ions (Ca(2+)) impact nearly every aspect of cellular life. This review
      examines the principles of Ca(2+) signaling, from changes in protein
      conformations driven by Ca(2+) to the mechanisms that control Ca(2+) levels in
      the cytoplasm and organelles. Also discussed is the highly localized nature of
      Ca(2+)-mediated signal transduction and its specific roles in excitability,
      exocytosis, motility, apoptosis, and transcription.

PMID- 18083097
TI  - Semen-derived amyloid fibrils drastically enhance HIV infection.
AB  - Sexual intercourse is the major route of HIV transmission. To identify endogenous
      factors that affect the efficiency of sexual viral transmission, we screened a
      complex peptide/protein library derived from human semen. We show that naturally
      occurring fragments of the abundant semen marker prostatic acidic phosphatase
      (PAP) form amyloid fibrils. These fibrils, termed Semen-derived Enhancer of Virus
      Infection (SEVI), capture HIV virions and promote their attachment to target
      cells, thereby enhancing the infectious virus titer by several orders of
      magnitude. Physiological concentrations of SEVI amplified HIV infection of T
      cells, macrophages, ex vivo human tonsillar tissues, and transgenic rats in vivo,
      as well as trans-HIV infection of T cells by dendritic or epithelial cells.
      Amyloidogenic PAP fragments are abundant in seminal fluid and boost semen
      mediated enhancement of HIV infection. Thus, they may play an important role in
      sexual transmission of HIV and could represent new targets for its prevention.

PMID- 18083098
TI  - Subcellular discharge of a serine protease mediates release of invasive malaria
      parasites from host erythrocytes.
AB  - The most virulent form of malaria is caused by waves of replication of blood
      stages of the protozoan pathogen Plasmodium falciparum. The parasite divides
      within an intraerythrocytic parasitophorous vacuole until rupture of the vacuole
      and host-cell membranes releases merozoites that invade fresh erythrocytes to
      repeat the cycle. Despite the importance of merozoite egress for disease
      progression, none of the molecular factors involved are known. We report that,
      just prior to egress, an essential serine protease called PfSUB1 is discharged
      from previously unrecognized parasite organelles (termed exonemes) into the
      parasitophorous vacuole space. There, PfSUB1 mediates the proteolytic maturation
      of at least two essential members of another enzyme family called SERA.
      Pharmacological blockade of PfSUB1 inhibits egress and ablates the invasive
      capacity of released merozoites. Our findings reveal the presence in the malarial
      parasitophorous vacuole of a regulated, PfSUB1-mediated proteolytic processing
      event required for release of viable parasites from the host erythrocyte.

PMID- 18083099
TI  - Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by
      COMPASS.
AB  - COMPASS, the yeast homolog of the mammalian MLL complex, is a histone H3 lysine 4
      (H3K4) methylase consisting of Set1 (KMT2) and seven other polypeptides,
      including Cps35, the only essential subunit. Histone H2B monoubiquitination by
      Rad6/Bre1 is required for both H3K4 methylation by COMPASS, and H3K79 methylation
      by Dot1. However, the molecular mechanism for such histone crosstalk is poorly
      understood. Here, we demonstrate that histone H2B monoubiquitination controls the
      binding of Cps35 with COMPASS complex. Cps 35 is required for COMPASS' catalytic
      activity in vivo, and the addition of exogenous purified Cps35 to COMPASS
      purified from a Deltarad6 background results in the generation of a methylation
      competent COMPASS. Cps35 associates with the chromatin of COMPASS-regulated genes
      in a H2BK123 monoubiquitination-dependent but Set1-independent manner. Cps35 is
      also required for proper H3K79 trimethylation. These findings offer insight into
      the molecular role of Cps35 in translating the H2B monoubiquitination signal into
      H3 methylation.

PMID- 18083100
TI  - Dual role for argonautes in microRNA processing and posttranscriptional
      regulation of microRNA expression.
AB  - MicroRNAs are small endogenous noncoding RNAs involved in posttranscriptional
      gene regulation. During microRNA biogenesis, Drosha and Dicer process the primary
      transcript (pri-miRNA) through a precursor hairpin (pre-miRNA) to the mature
      miRNA. The miRNA is incorporated into the RNA-Induced Silencing Complex (RISC)
      with Argonaute proteins, the effector molecules in RNA interference (RNAi). Here,
      we show that all Argonautes elevate mature miRNA expression
      posttranscriptionally, independent of RNase activity. Also, we identify a role
      for the RISC slicer Argonaute2 (Ago2) in cleaving the pre-miRNA to an additional
      processing intermediate, termed Ago2-cleaved precursor miRNA or ac-pre-miRNA.
      This endogenous, on-pathway intermediate results from cleavage of the pre-miRNA
      hairpin 12 nucleotides from its 3'-end. By analogy to siRNA processing, Ago2
      cleavage may facilitate removal of the nicked passenger strand from RISC after
      maturation. The multiple roles of Argonautes in the RNAi effector phase and miRNA
      biogenesis and maturation suggest coordinate regulation of microRNA expression
      and function.

PMID- 18083101
TI  - let-7 regulates self renewal and tumorigenicity of breast cancer cells.
AB  - Cancers may arise from rare self-renewing tumor-initiating cells (T-IC). However,
      how T-IC self renewal, multipotent differentiation, and tumorigenicity are
      maintained remains obscure. Because miRNAs can regulate cell-fate decisions, we
      compared miRNA expression in self-renewing and differentiated cells from breast
      cancer lines and in breast T-IC (BT-IC) and non-BT-IC from 1 degrees breast
      cancers. let-7 miRNAs were markedly reduced in BT-IC and increased with
      differentiation. Infecting BT-IC with let-7-lentivirus reduced proliferation,
      mammosphere formation, and the proportion of undifferentiated cells in vitro and
      tumor formation and metastasis in NOD/SCID mice, while antagonizing let-7 by
      antisense oligonucleotides enhanced in vitro self renewal of non-T-IC. Increased
      let-7 paralleled reduced H-RAS and HMGA2, known let-7 targets. Silencing H-RAS in
      a BT-IC-enriched cell line reduced self renewal but had no effect on
      differentiation, while silencing HMGA2 enhanced differentiation but did not
      affect self renewal. Therefore let-7 regulates multiple BT-IC stem cell-like
      properties by silencing more than one target.

PMID- 18083102
TI  - TAM receptors are pleiotropic inhibitors of the innate immune response.
AB  - The activation of Toll-like receptors (TLRs) in dendritic cells (DCs) triggers a
      rapid inflammatory response to pathogens. However, this response must be tightly
      regulated because unrestrained TLR signaling generates a chronic inflammatory
      milieu that often leads to autoimmunity. We have found that the TAM receptor
      tyrosine kinases-Tyro3, Axl, and Mer-broadly inhibit both TLR and TLR-induced
      cytokine-receptor cascades. Remarkably, TAM inhibition of inflammation is
      transduced through an essential stimulator of inflammation-the type I interferon
      receptor (IFNAR)-and its associated transcription factor STAT1. TLR induction of
      IFNAR-STAT1 signaling upregulates the TAM system, which in turn usurps the IFNAR
      STAT1 cassette to induce the cytokine and TLR suppressors SOCS1 and SOCS3. These
      results illuminate a self-regulating cycle of inflammation, in which the
      obligatory, cytokine-dependent activation of TAM signaling hijacks a
      proinflammatory pathway to provide an intrinsic feedback inhibitor of both TLR-
      and cytokine-driven immune responses.

PMID- 18083103
TI  - Growth arrest and autophagy are required for salivary gland cell degradation in
      Drosophila.
AB  - Autophagy is a catabolic process that is negatively regulated by growth and has
      been implicated in cell death. We find that autophagy is induced following growth
      arrest and precedes developmental autophagic cell death of Drosophila salivary
      glands. Maintaining growth by expression of either activated Ras or positive
      regulators of the class I phosphoinositide 3-kinase (PI3K) pathway inhibits
      autophagy and blocks salivary gland cell degradation. Developmental degradation
      of salivary glands is also inhibited in autophagy gene (atg) mutants. Caspases
      are active in PI3K-expressing and atg mutant salivary glands, and combined
      inhibition of both autophagy and caspases increases suppression of gland
      degradation. Further, induction of autophagy is sufficient to induce premature
      cell death in a caspase-independent manner. Our results provide in vivo evidence
      that growth arrest, autophagy, and atg genes are required for physiological
      autophagic cell death and that multiple degradation pathways cooperate in the
      efficient clearance of cells during development.

PMID- 18083104
TI  - Homeostatic levels of p62 control cytoplasmic inclusion body formation in
      autophagy-deficient mice.
AB  - Inactivation of constitutive autophagy results in formation of cytoplasmic
      protein inclusions and leads to liver injury and neurodegeneration, but the
      details of abnormalities related to impaired autophagy are largely unknown. Here
      we used mouse genetic analyses to define the roles of autophagy in the
      aforementioned events. We report that the ubiquitin- and LC3-binding protein
      "p62" regulates the formation of protein aggregates and is removed by autophagy.
      Thus, genetic ablation of p62 suppressed the appearance of ubiquitin-positive
      protein aggregates in hepatocytes and neurons, indicating that p62 plays an
      important role in inclusion body formation. Moreover, loss of p62 markedly
      attenuated liver injury caused by autophagy deficiency, whereas it had little
      effect on neuronal degeneration. Our findings highlight the unexpected role of
      homeostatic level of p62, which is regulated by autophagy, in controlling
      intracellular inclusion body formation, and indicate that the pathologic process
      associated with autophagic deficiency is cell-type specific.

PMID- 18083105
TI  - The classical complement cascade mediates CNS synapse elimination.
AB  - During development, the formation of mature neural circuits requires the
      selective elimination of inappropriate synaptic connections. Here we show that
      C1q, the initiating protein in the classical complement cascade, is expressed by
      postnatal neurons in response to immature astrocytes and is localized to synapses
      throughout the postnatal CNS and retina. Mice deficient in complement protein C1q
      or the downstream complement protein C3 exhibit large sustained defects in CNS
      synapse elimination, as shown by the failure of anatomical refinement of
      retinogeniculate connections and the retention of excess retinal innervation by
      lateral geniculate neurons. Neuronal C1q is normally downregulated in the adult
      CNS; however, in a mouse model of glaucoma, C1q becomes upregulated and
      synaptically relocalized in the adult retina early in the disease. These findings
      support a model in which unwanted synapses are tagged by complement for
      elimination and suggest that complement-mediated synapse elimination may become
      aberrantly reactivated in neurodegenerative disease.

PMID- 18083106
TI  - cis-Regulatory changes in Kit ligand expression and parallel evolution of
      pigmentation in sticklebacks and humans.
AB  - Dramatic pigmentation changes have evolved within most vertebrate groups,
      including fish and humans. Here we use genetic crosses in sticklebacks to
      investigate the parallel origin of pigmentation changes in natural populations.
      High-resolution mapping and expression experiments show that light gills and
      light ventrums map to a divergent regulatory allele of the Kit ligand (Kitlg)
      gene. The divergent allele reduces expression in gill and skin tissue and is
      shared by multiple derived freshwater populations with reduced pigmentation. In
      humans, Europeans and East Asians also share derived alleles at the KITLG locus.
      Strong signatures of selection map to regulatory regions surrounding the gene,
      and admixture mapping shows that the KITLG genomic region has a significant
      effect on human skin color. These experiments suggest that regulatory changes in
      Kitlg contribute to natural variation in vertebrate pigmentation, and that
      similar genetic mechanisms may underlie rapid evolutionary change in fish and
      humans.

PMID- 18083108
TI  - SnapShot: Wnt/beta-catenin signaling.

PMID- 18083107
TI  - Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung
      cancer.
AB  - Despite the success of tyrosine kinase-based cancer therapeutics, for most solid
      tumors the tyrosine kinases that drive disease remain unknown, limiting our
      ability to identify drug targets and predict response. Here we present the first
      large-scale survey of tyrosine kinase activity in lung cancer. Using a
      phosphoproteomic approach, we characterize tyrosine kinase signaling across 41
      non-small cell lung cancer (NSCLC) cell lines and over 150 NSCLC tumors. Profiles
      of phosphotyrosine signaling are generated and analyzed to identify known
      oncogenic kinases such as EGFR and c-Met as well as novel ALK and ROS fusion
      proteins. Other activated tyrosine kinases such as PDGFRalpha and DDR1 not
      previously implicated in the genesis of NSCLC are also identified. By focusing on
      activated cell circuitry, the approach outlined here provides insight into cancer
      biology not available at the chromosomal and transcriptional levels and can be
      applied broadly across all human cancers.

PMID- 18083109
TI  - Monosialylated biantennary N-glycoforms containing GalNAc-GlcNAc antennae
      predominate when human EPO is expressed in goat milk.
AB  - Recently, our group reported the expression of recombinant human erythropoietin
      in goat milk (rhEPO-milk) as well as in the mammary epithelial cell line GMGE
      (EPO-GMGE) by cell culture using the adenoviral transduction system. N
      Glycosylation characterization of rhEPO-milk by Normal-Phase HPLC profiling of
      the fluorophore, 4-aminobenzoic acid-labeled enzymatically released N-glycan pool
      from rhEPO-goat milk, combined with MALDI, ESI-MS and LC/MS, revealed that low
      branched, core-fucosylated, N-glycans predominate. The labeled N-glycans were
      separated into neutral and charged fractions by anion exchange chromatography and
      the charged N-glycans were found to be mostly alpha2,6-monosialylated with Neu5Ac
      or Neu5Gc in a ratio of 1:1. Unlike the N-glycans from rhEPO produced in CHO
      cells, where the glycans are multiantennary highly sialylated, core-fucosylated
      oligosaccahrides, or even in the goat mammary gland epithelial cell line cultured
      in vitro in which multiantennary, core- and outer-arm fucosylated, monosialylated
      N-glycans are the most abundant species, a large proportion of the N-glycans from
      rhEPO-milk were monosialylated, biantennary, antennae mostly terminating with the
      more unusual GalNAc-GlcNAc motive and without outer-arm fucosylation. These
      findings, emphasizing the difference in the N-glycan repertoire between the rhEPO
      milk and EPO-GMGE, are consistent with the principle that glycosylation is cell
      type dependent and that the cell environment is crucial as well.

PMID- 18083110
TI  - Intra-colonic administration of the TLR7 agonist R-848 induces an acute local and
      systemic inflammation in mice.
AB  - Imidazoquinoline compounds, such as resiquimod (R-848), are well known topically
      active immune modifiers that bind to toll-like receptor 7 (TLR7). The aim of this
      study was to characterize the R-848 induced inflammatory response in mice and to
      validate the response using methyl-prednisolone and anti-TNF antibody. Intra
      colonic application of R-848 to BALB/c mice induced a systemic transient
      elevation of TNF, CXCL1, IL-6, and IL-12p40 and a colonic elevation of
      cytokines/chemokines and iNOS, without infiltration of immune cells or epithelial
      destruction. Treatment with methyl-prednisolone or anti-TNF antibody attenuated
      the systemic (TNF, IL-6, IL-12p40, and CXCL1) and local (colonic TNF and iNOS
      mRNA expression) response induced by R-848. In summary, intra-colonic
      administration of R-848 induces an acute systemic and local inflammatory
      response, which can be attenuated by steroids or anti-TNF antibody. We suggest
      that the R-848 inflammatory model can be useful in future validation of new drugs
      for gastrointestinal inflammatory conditions.

PMID- 18083111
TI  - TLR4 signaling in cancer cells promotes chemoattraction of immature dendritic
      cells via autocrine CCL20.
AB  - Toll-like receptors (TLRs) are involved in the production of inflammatory
      mediators upon specific ligands stimuli. Chemokines are important inflammatory
      mediators capable of chemoattracting diverse immune cells. In addition to normal
      immune cells, the expression of TLRs and chemokines has been detected in various
      tumor cells. However, the roles of TLRs and chemokines expressed by tumor cells
      in the processes of tumor progression and immune escape have not been fully
      elucidated. Here we report that TLR4 ligation by lipopolysaccharide (LPS)
      significantly promotes CT-26 colon cancer cells to produce chemokine CCL20 via
      activation of TLR4 signaling pathways. We find that LPS treatment of CT-26 cells
      can significantly increase the chemoattraction of immature dendritic cells (DC)
      by the autocrine CCL20. Our studies suggest that TLR4 expressed by tumor cells
      may be involved in the induction of chemokines like CCL20, providing a potential
      linkage between chronic inflammation and tumor immune escape.

PMID- 18083112
TI  - Identification of lipopolysaccharide binding site on high molecular weight
      kininogen.
AB  - Plasma kallikrein kinin system (KKS) activation along with its cellular receptors
      expression are increased after injury and in patients with septic shock,
      hypotensive bacteremia and rhesus monkey infected with Salmonella typhimurium.
      KKS signaling cascade is activated by activated factor XII (FXIIa, Hageman
      factor)- and prolylcarboxypeptidase (PRCP)-dependent pathways on endothelial
      cells. Among the many entities that comprise the KKS, high molecular weight
      kininogen (HK), a bradykinin precursor, is critical in the assembly and
      activation of this system. HK is primarily expressed in the liver and secreted
      into the bloodstream. The activation of the KKS influences the permeability of
      the endothelium by liberating bradykinin (BK) from HK. BK is a potent
      inflammatory peptide which stimulates constitutive bradykinin B2 and inducible B1
      receptors to release nitric oxide and prostacyclin. Regardless of the triggers,
      PK can only be activated on HK bound to the artificial negatively charged or to
      cell membrane surfaces. Since LPS has a negatively charged moiety and the ability
      to induce inflammatory responses in human, we determined the interaction between
      LPS and HK. HKH19 (HK cell binding site) and heparin inhibited LPS binding to HK
      with IC(50)s of 15nM and 20 microg/ml, respectively. C1-inhibitor and N
      acetylglucosamine glycan inhibited LPS binding to HK with IC(50)s of about 10
      microg/ml and 10mM, respectively. This novel study underscores the implication of
      HK in infection. We propose that HKH19, heparin, and C1-inhibitor present
      therapeutic potential for the treatment of sepsis and hypotensive bacteremia.

PMID- 18083113
TI  - Mutational analysis of type IV collagen alpha5 chain, with respect to
      heterotrimer formation.
AB  - Alport syndrome (AS) is caused by mutations in type IV collagen alpha3, alpha4,
      and alpha5 chains. The three chains form a heterotrimer. In this study, we
      introduced 12 kinds of missense and three kinds of nonsense mutations,
      corresponding to AS mutations, into the NC1 domain of alpha5(IV) and
      characterized the mutant chains. Nine alpha5(IV) chains with amino acid
      substitutions and all three truncated alpha5(IV) chains did not form a
      heterotrimer and were not secreted from cells. Three alpha5(IV) chains with amino
      acid substitutions did, however, form heterotrimers in cells, but these were not
      secreted from cells. These findings indicate that a defect in heterotrimer
      formation is the main molecular mechanism underlying the pathogenesis of AS
      caused by mutation in the NC1 domain. We also showed that even a single amino
      acid deletion in the carboxyl-terminal region markedly affected the
      heterotrimerization, indicating that the carboxyl-terminal end is indispensable
      for heterotrimer formation.

PMID- 18083115
TI  - MsrA protects cardiac myocytes against hypoxia/reoxygenation induced cell death.
AB  - Reactive oxygen species (ROS) are critical in tissue responses to ischemia
      reperfusion. The enzyme methionine sulfoxide reductase-A (MsrA) is capable of
      protecting cells against oxidative damage by reversing damage to proteins caused
      by methionine oxidation or by decreasing ROS through a scavenger mechanism. The
      current study employed adenovirus mediated over-expression of MsrA in primary
      neonatal rat cardiac myocytes to determine the effect of this enzyme in
      protecting against hypoxia/reoxygenation in this tissue. Cells were transduced
      with MsrA encoding adenovirus and subjected to hypoxia/reoxygenation. Apoptotic
      cell death was decreased by greater than 45% in cells over-expressing MsrA
      relative to cells transduced with a control virus. Likewise total cell death as
      determined by levels of LDH release was dramatically decreased by MsrA over
      expression. These observations indicate that MsrA is protective against
      hypoxia/reoxygenation stress in cardiac myocytes and point to MsrA as an
      important therapeutic target for ischemic heart disease.

PMID- 18083114
TI  - Spatially and temporally regulated alpha6 integrin cleavage during Xenopus laevis
      development.
AB  - The alpha6 integrin is essential for early nervous system development in Xenopus
      laevis. We have previously reported a uPA cleaved form of integrin alpha6
      (alpha6p), in invasive human prostate cancer tissue, whose presence correlates
      with increased migration and invasive capacity. We now report that alpha6 is
      cleaved during the normal development of Xenopus in a spatially and temporally
      controlled manner. In addition, unlike normal mammalian tissues, which lack
      alpha6p, the major form of the alpha6 integrin present in adult Xenopus is
      alpha6p. The protease responsible for the cleavage in mammals, uPA, is not
      involved in the cleavage of Xenopus alpha6. Finally, overexpression of a
      mammalian alpha6 mutant which cannot be cleaved leads to developmental
      abnormalities suggesting a potential role for the cleavage in development.

PMID- 18083116
TI  - Calyculin A retraction of mature megakaryocytes proplatelets from embryonic stem
      cells.
AB  - Platelets are produced by megakaryocytes (MKs) through proplatelet formation
      (PPF), or cytoplasmic extensions, in vitro. Through the use of video-enhanced
      light microscopy, as well as localization of cytoskeletal proteins by confocal
      microscopy, the reaction of fully mature MK proplatelets, derived from murine
      embryonic stem cells, to various agents was studied. Calyculin A (protein
      phosphatase 1/2A inhibitor) treatment induced proplatelet retraction. In MKs with
      PPF, the expression of actin, myosin IIA, monophosphorylated myosin light chain
      (MLC-P1), and diphosphorylated myosin light chain (MLC-P2) was diffusely located.
      Following calyculin A treatment, actin was diffusely localized in retracted MKs
      and was expressed particularly in the periphery. MLC-P1 was also localized
      primarily in the periphery; however, MLC-P2 was expressed mostly in the inner
      area of proplatelets. Protein phosphatase inhibitors may result in increased
      hyperphosphorylation of localized MLC, which could alter the balance of
      actomyosin force in a cell, and therefore induce proplatelets retraction.

PMID- 18083117
TI  - Effect of external torque on the ATP-driven rotation of F1-ATPase.
AB  - F(1)-ATPase is a rotary molecular motor powered by the torque generated by
      another rotary motor F(0) to synthesize ATP in vivo. Therefore elucidation of the
      behavior of F(1) under external torque is very important. Here, we applied
      controlled external torque by electrorotation and investigated the ATP-driven
      rotation for the first time. The rotation was accelerated by assisting torque and
      decelerated by hindering torque, but F(1) rarely showed rotations in the ATP
      synthesis direction. This is consistent with the prediction by models based on
      the assumption that the rotation is tightly coupled to ATP hydrolysis and
      synthesis. At low ATP concentrations (2 and 5 microM), 120 degrees stepwise
      rotation was observed. Due to the temperature rise during experiment,
      quantitative interpretation of the data is difficult, but we found that the
      apparent rate constant of ATP binding clearly decreased by hindering torque and
      increased by assisting torque.

PMID- 18083118
TI  - Epibatidine binds to four sites on the Torpedo nicotinic acetylcholine receptor.
AB  - The nicotinic acetylcholine receptor (nAChR) from Torpedo electric organ is a
      pentamer of homologous subunits. This receptor is generally thought to carry two
      high affinity sites for agonists under equilibrium conditions. Here we
      demonstrate directly that each Torpedo nAChR carries at least four binding sites
      for the potent neuronal nAChR agonist, epibatidine, i.e., twice as many sites as
      for alpha-bungarotoxin. Using radiolabeled ligand binding techniques, we show
      that the binding of [(3)H]-(+/-)-epibatidine is heterogeneous and is
      characterized by two classes of binding sites with equilibrium dissociation
      constants of about 15nM and 1muM. These classes of sites exist in approximately
      equal numbers and all [(3)H]-(+/-)-epibatidine binding is competitively displaced
      by acetylcholine, suberyldicholine and d-tubocurarine. These results provide
      further evidence for the complexity of agonist binding to the nAChR and
      underscore the difficulties in determining simple relationships between site
      occupancy and functional responses.

PMID- 18083119
TI  - Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic
      mice.
AB  - We previously proposed that hyperglycemia-induced mitochondrial ROS
      overproduction is a key event in the development of diabetic complications. In
      this study, we established a novel transgenic mouse (eMnSOD-Tg), which
      specifically expressed MnSOD in endothelial cells, by employing a Tie2
      promoter/enhancer, and investigated the impact of mitochondrial ROS production on
      diabetic retinopathy in vivo. Using immunohistochemistry, overexpression of MnSOD
      in endothelial cells was confirmed in eMnSOD-Tg mice. By introduction of diabetes
      by streptozotocin, levels of urinary 8-hydroxydeoxyguanosine, a marker of
      mitochondrial oxidative stress, and expression of VEGF mRNA and protein and
      fibronectin mRNA in retinas were increased in wild-type littermates. However,
      these observations were ameliorated in eMnSOD-Tg mice, although control and
      eMnSOD-Tg mice showed a comparable level of hyperglycemia. In the present study,
      we newly developed a line of transgenic mice, which specifically express MnSOD in
      endothelium. In addition, overexpression of mitochondrial-specific SOD in
      endothelium could prevent diabetic retinopathy in vivo.

PMID- 18083120
TI  - Epidermal growth factor (EGF) receptor targeted delivery of PEGylated adenovirus.
AB  - A biotin-polyethylene glycol (PEG)-epidermal growth factor (EGF) conjugate was
      immobilized onto the surface of avidin-modified adenovirus (ADV-Avi) via biotin
      avidin interaction to deliver ADV specifically to EGF receptor over-expressing
      cancer cells. ADV-Avi/biotin-PEG-EGF complexes showed greatly enhanced
      intracellular uptake of ADV particles for an EGF receptor positive cell line
      (A431 cells), compared to naked or PEG alone immobilized ADV. ADV coding an
      exogenous GFP gene was used to quantitatively evaluate the level of GFP
      expression. ADV-Avi/biotin-PEG-EGF complexes also exhibited significantly
      increased extent of GFP expression for A431 cells, but not for MCF-7 cells (an
      EGF receptor deficient cell line), suggesting that retargeting of ADV to specific
      cells occurred by tethering of a cell-specific targeting ligand to the distal end
      of a PEG chain anchored onto the surface of ADV. This study demonstrates that ADV
      Avi/biotin-PEG-EGF construct systems can be applied for cell-specific delivery of
      ADV with simultaneously reducing innate immune responses.

PMID- 18083121
TI  - Role of L-carnitine in the modulation of immune response in aged rats.
AB  - BACKGROUND: The immune system undergoes alterations in functions with aging which
      results in progressive deterioration in the ability to respond to infection. The
      importance of nutrients in regulating immune responses has widened attempts on
      interventions that improve immune functions with aging. L-carnitine serves as a
      vital factor in the mitochondrial transport of fatty acids, a process essential
      for fatty acid oxidation and energy release. L-carnitine is categorized as a
      conditionally essential nutrient factor and its concentrations are reported to be
      decreased with aging. METHODS: The immunomodulatory role of L-carnitine was
      assessed in aged rats after administration of L-carnitine (300 mg/kg body
      weight/day) for 7, 14 and 21 days by evaluating neutrophil functions, delayed
      type hypersensitivity (DTH) responses and immunoglobulin concentrations. RESULTS:
      Aged animals exhibited decreased non-specific immune functions, delayed-type
      hypersensitivity responses and immunoglobulin concentrations compared to younger
      controls. Treatment with L-carnitine improved neutrophil functions, delayed-type
      hypersensitivity responses and the concentrations of immunoglobulins A and G in
      aged animals in a significant manner. However L-carnitine treatment did not have
      any impact on IgM concentration and type responses. CONCLUSIONS: This study
      demonstrated that aging is associated with a decline in immune functions and
      supplementing L-carnitine had a positive effect in improving immune responses in
      aged animals.

PMID- 18083122
TI  - Polymorphism in the human C-reactive protein (CRP) gene, serum concentrations of
      CRP, and the difference between intracranial and extracranial atherosclerosis.
AB  - BACKGROUND: C-reactive protein, a proinflammatory factor, is involved in the
      development of atherosclerosis. The CRP 1059G>C polymorphism appeared to be a
      susceptive marker for atherosclerosis. We investigated the relationship of the
      distribution of cerebral atherosclerosis with triggered serum CRP concentrations
      following acute ischemic stroke/transient ischemic attack (IS/TIA) and CRP
      1059G>C polymorphism. METHODS: We recruited 222 IS/TIA patients (122 with only
      intracranial atherosclerotic lesions and 100 with isolated extracranial
      atherosclerotic lesions) and 227 controls. Intra- and extracranial
      atherosclerotic lesions were determined by digital subtraction angiography. Serum
      CRP concentrations were measured by particle-enhanced immunonephelometry assay.
      CRP 1059G>C genotypes were obtained through PCR amplification and restriction
      enzyme digestion. RESULTS: CRP concentrations were significantly higher in intra-
      and extracranial groups than in controls. No significant difference was found in
      CRP concentrations between intra- and extracranial groups. The CRP 1059G>C single
      nucleotide polymorphism did not influence CRP serum concentrations. CRP genotype
      and allele frequencies did not differ significantly between patients and
      controls. However, the frequencies of GC genotype and C allele were significantly
      higher in extracranial group than that in intracranial group. The GC individuals
      showed a higher risk of extracranial atherosclerosis compared with GG individuals
      (OR 3.41; 95%CI, 1.124-10.347; P=0.030). CONCLUSIONS: Serum CRP is associated
      with cerebral atherosclerotic disease. CRP 1059G>C polymorphism is one possible
      genetic determinant for the difference between intra- and extracranial
      atherosclerosis.

PMID- 18083123
TI  - Proton transfer in the photosynthetic reaction center of Blastochloris viridis.
AB  - Photosynthetic reaction centers of Blastochloris viridis require two quanta of
      light to catalyse a two-step reduction of their secondary ubiquinone Q(B) to
      ubiquinol. We employed capacitive potentiometry to follow the voltage changes
      that were caused by the accompanying transmembrane proton displacements. At pH
      7.5 and 20 degrees C, the Q(B)-related voltage generation after the first flash
      was contributed by a fast, temperature-independent component with a time constant
      of approximately 30 micros and a slower component of approximately 200 micros
      with activation energy (E(a)) of 50 kJ/mol. The kinetics after the second flash
      featured temperature-independent components of 5 micros and 200 micros followed
      by a component of 600 micros with E(a) approximately 60 kJ/mol.

PMID- 18083124
TI  - Roscovitine inhibits ERK1/2 activation induced by angiotensin II in vascular
      smooth muscle cells.
AB  - Roscovitine is a potent CDK inhibitor often used as a biological tool in cell
      cycle studies, but its working mechanism and real targets in vascular smooth
      muscle cells (VSMCs) remain unclear. In this study, we observed that ERK1/2
      phosphorylation induced by Ang II was abrogated by pretreating VSMCs with
      roscovitine for 15h. Pretreating VSMCs with roscovitine also inhibited Ang II
      induced c-Jun expression and phosphorylation. We further demonstrated that
      roscovitine could suppress the DNA binding activity of c-Jun and activation of
      angiotensinogen promoter by Ang II. These results suggest that roscovitine
      represses Ang II-induced angiotensinogen expression by inhibiting activation of
      ERK1/2 and c-Jun.

PMID- 18083125
TI  - Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling
      through LRP6.
AB  - Binding of Wnt to Frizzled, and either of two members of the low-density
      lipoprotein receptor-related protein family, LRP5/6, leads to beta-catenin
      activation by a poorly understood mechanism. LRP5/6 exhibit five highly conserved
      PPPS/TP motifs in their intracellular region, among which the first PPPS/TP site
      is rapidly phosphorylated upon Wnt stimulation. By the use of full-length LRP6
      mutants harboring multiple mutations involving the five PPPS/TP motifs, we found
      that this first PPPS/TP phosphoacceptor site is alone not sufficient or strictly
      necessary for beta-catenin activation. Instead, we show that each LRP6 PPPS/TP
      motif contributes in a combinatorial fashion to activate the canonical Wnt-beta
      catenin pathway.

PMID- 18083126
TI  - Single particle analysis of thylakoid proteins from Thermosynechococcus elongatus
      and Synechocystis 6803: localization of the CupA subunit of NDH-1.
AB  - The larger protein complexes of the cyanobacterial photosynthetic membrane of
      Thermosynechoccus elongatus and Synechocystis 6803 were studied by single
      particle electron microscopy after detergent solubilization, without any
      purification steps. Besides the "standard" L-shaped NDH-1L complex, related to
      complex I, large numbers of a U-shaped NDH-1MS complex were found in both
      cyanobacteria. In membranes from Synechocystis DeltacupA and DeltacupA/cupB
      mutants the U-shaped complexes were absent, indicating that CupA is responsible
      for the U-shape by binding at the tip of the membrane-bound arm of NDH-1MS.
      Comparison of membranes grown under air levels of CO(2) or 3% CO(2) indicates
      that the number of NDH-1MS particles is 30-fold higher under low-CO(2).

PMID- 18083127
TI  - The xanthophyll cycle pool size controls the kinetics of non-photochemical
      quenching in Arabidopsis thaliana.
AB  - Arabidopsis plants overexpressing beta-carotene hydroxylase 1 accumulate over
      double the amount of zeaxanthin present in wild-type plants. The final amplitude
      of non-photochemical quenching (NPQ) was found to be the same in these plants,
      but the kinetics were different. The formation and relaxation of NPQ consistently
      correlated with the de-epoxidation state of the xanthophyll cycle pool and not
      the amount of zeaxanthin. These data indicate that zeaxanthin and violaxanthin
      antagonistically regulate the switch between the light harvesting and
      photoprotective modes of the light harvesting system and show that control of the
      xanthophyll cycle pool size is necessary to optimize the kinetics of NPQ.

PMID- 18083128
TI  - F2L, a peptide derived from heme-binding protein, inhibits LL-37-induced cell
      proliferation and tube formation in human umbilical vein endothelial cells.
AB  - F2L, a peptide derived from heme-binding protein, was originally identified as an
      endogenous ligand for formyl peptide receptor-like (FPRL)2. Previously, we
      reported that F2L inhibits FPR and FPRL1-mediated signaling in neutrophils. Since
      endothelial cells express functional FPRL1, we examined the effect of F2L on LL
      37 (an FPRL1 agonist)-induced signaling in human umbilical vein endothelial cells
      (HUVECs). F2L stimulated the chemotactic migration in HUVECs. However, F2L
      inhibited FPRL1 activity, resulting in the inhibition of cell proliferation and
      tube formation induced by LL-37 in HUVECs. We suggest that F2L will potentially
      be useful in the study of FPRL1 signaling and the development of drugs to treat
      diseases involving the FPRL1 in the vascular system.

PMID- 18083129
TI  - Laccase of Cyathus bulleri: structural, catalytic characterization and expression
      in Escherichia coli.
AB  - Cyathus bulleri, a ligninolytic fungus, produces a single laccase the internal
      peptides (3) of which bear similarity to laccases of several white rot fungi.
      Comparison of the total amino acid composition of this laccase with several
      fungal laccases indicated dissimilarity in the proportion of some basic and
      hydrophobic amino acids. Analysis of the circular dichroism spectrum of the
      protein indicated 37% alpha-helical, 26% beta-sheet and 38% random coil content
      which differed significantly from that in the solved structures of other
      laccases, which contain higher beta-sheet structures. The critical role of the
      carboxylic group containing amino acids was demonstrated by determining the
      kinetic parameters at different pH and this was confirmed by the observation that
      a critical Asp is strongly conserved in both Ascomycete and Basidiomycete
      laccases. The enzyme was denatured in the presence of a number of denaturing
      agents and refolded back to functional state with copper. In the folding
      experiments under alkaline conditions, zinc could replace copper in restoring
      100% of laccase activity indicating the non-essential role of copper in this
      laccase. The laccase was expressed in Escherichia coli by a modification of the
      ligation-anchored PCR approach making it the first fungal laccase to be expressed
      in a bacterial host. The laccase sequence was confirmed by way of analysis of a
      435 bp sequence of the insert.

PMID- 18083130
TI  - Aggregation of S6 in a quasi-native state by sub-micellar SDS.
AB  - Anionic surfaces promote protein fibrillation in vitro and in vivo. Monomeric SDS
      has also been shown to stimulate this process. We describe the dynamics of
      conformational changes and aggregative properties of the model protein S6 at sub
      micellar SDS concentrations. S6 exhibits a rich and pH-sensitive diversity in
      conformational changes around 0.2-2 mM SDS, in which several transitions occur
      over time scales spanning milliseconds to hours. Monomeric SDS readily
      precipitates S6 within minutes at pH-values of 5 and below to form states able to
      bind the fibril-specific dye thioflavin T. At pH 5.5, the process is much slower
      and shows a mutagenesis-sensitive lag, leading to different forms of organized
      but not classically fibrillar aggregates with native-like levels of secondary
      structure, although the tertiary structure is significantly rearranged. The slow
      aggregation process may be linked to conformational changes that occur at the
      second-time scale in the same SDS concentration range, leading to an altered
      structure, possibly with unfolding around the C-terminal helix. The S6 aggregates
      may be differently trapped states, equivalent to pre-fibrillar structures seen at
      early stages in the fibrillation process for other proteins. The low quantities
      of anionic species required suggest that the aggregates may have parallels in
      vivo.

PMID- 18083131
TI  - Exploring functional genomics for drug target and therapeutics discovery in
      Plasmodia.
AB  - Functional genomics approaches are indispensable tools in the drug discovery
      arena and have recently attained increased attention in antibacterial drug
      discovery research. However, the application of functional genomics to post
      genomics research of Plasmodia is still in comparatively early stages.
      Nonetheless, with this genus having the most species sequenced of any eukaryotic
      organism so far, the Plasmodia could provide unique opportunities for the study
      of intracellular eukaryotic pathogens. This review presents the status quo of
      functional genomics of the malaria parasite including descriptions of the
      transcriptome, proteome and interactome. We provide examples for the in silico
      mining of the X-ome data sets and illustrate how X-omic data from drug challenged
      parasites might be used in elucidating amongst others, the mode-of-action of
      inhibitory compounds, validate potential targets and discover novel
      targets/therapeutics.

PMID- 18083132
TI  - The ultrastructural research of liver in experimental obstructive jaundice and
      effect of honey.
AB  - BACKGROUND: To examine the effects of honey on oxidative stress and apoptosis in
      experimental obstructive jaundice model. METHOD: Thirty rats were divided into 3
      groups: group I, sham-operated; group II, ligation and division of the common
      bile duct (BDL); group III, BDL followed by oral supplementation of honey 10
      g/kg/d. Liver samples were examined under light microscope and transmission
      electron microscope. Hepatocyte apoptosis was quantitated using the terminal
      deoxy-nucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labeling (TUNEL) assay. Plasma and blood malondialdehyde (MDA) and glutation
      activities were measured for determining the oxidative stress. RESULTS: The liver
      levels of MDA and GSH were significantly different between the honey and BDL
      groups (P = .006 and .001, respectively). However, there was no significant
      difference between the plasma MDA and GSH levels of these groups (P > .05). In
      group III, significant reductions in the size of enlarged hepatocytes and the
      edema were demonstrated. The dilatation of the bile canaliculi dramatically
      turned to original dimention. By TUNEL assay, it was shown that administration of
      honey decreased the number of apoptotic cells. CONCLUSIONS: In the present study,
      we found that honey diminished the negative effects of BDL on the hepatic
      ultrastructure. We conclude that this effect might be due to its antioxidant and
      anti-inflammatory activities.

PMID- 18083133
TI  - Novel sutureless cholangiojejunostomy: initial experience with 11 cases.
AB  - BACKGROUND: It has become increasingly necessary to develop a reliable sutureless
      technique to replace the conventional hand-sewn one for carrying out bilioenteric
      anastomosis. METHODS: A new sutureless technique for cholangiojejunostomy is
      described, and a retrospective review was conducted of a prospectively collected
      database, which included 11 patients who underwent sutureless
      cholangiojejunostomy between April 2005 and July 2006. RESULTS: All patients
      successfully underwent sutureless cholangiojejunostomy, including
      choledochojejunostomy and hepaticojejunostomy. Median operative time was 13
      minutes. There were no mortalities and no postoperative morbidities directly
      related to cholangiojejunostomy. At a mean follow-up period of 8.2 months, no
      patients had evidence of anastomotic stricture, except for 1 patient who
      developed obstructive jaundice because the recurrent tumor was pressing against
      the hepaticojejunal anastomosis. CONCLUSIONS: Sutureless cholangiojejunostomy is
      simple, reliable, and feasible. Further larger-series studies, with longer follow
      up periods and involving further improvements of the technique, are necessary
      before this procedure can become routine.

PMID- 18083134
TI  - Basal cell-like (triple-negative) breast cancer, a predictor of distant
      metastasis in African American women.
AB  - BACKGROUND: The aim of this study was to evaluate the prognostic significance of
      the basal cell-like molecular breast cancer subtype with respect to locoregional
      recurrence and distant metastasis in African American women treated for breast
      cancer. METHODS: A retrospective analysis was performed of the tumor registry
      database for all African American women diagnosed and treated for breast cancer
      from 1998 to 2005 who had assessable data for all 3 markers: estrogen,
      progesterone, and Her-2/neu. RESULTS: A total of 372 patients were included in
      our study sample. Of these, 22 (6.1%) had locoregional recurrence, 35 (9.8%) had
      distant metastasis, and 301 (84.1%) had no evidence of breast tumor recurrence.
      The median follow-up time was 36 months. Compared with the other molecular
      subtypes the basal cell-like subtype showed a statistically significant
      association to distant metastasis: 15 (42.9%) vs 13 (37.1%), 4 (11.4%), and 3
      (8.6%) (P < .001), respectively, for luminal A, Her-2/neu, and luminal B
      subtypes. The basal cell-like subtype was an independent predictor of distant
      metastasis (odds ratio, 5.8; 95% confidence interval, 1.5-22.0, P = .009). The
      molecular subtypes showed no statistically significant difference with respect to
      locoregional treatment administered and tumor stage at time of diagnosis.
      CONCLUSIONS: The basal cell-like molecular breast cancer subtype is an
      independent predictor of distant metastasis in African American women.

PMID- 18083135
TI  - Serum tumor marker CA19-9 in the follow-up of patients with cystic
      echinococcosis.
AB  - BACKGROUND: The aim of this study was to compare results of the determination of
      carcinoembryonic antigen, carbohydrate antigens, alpha-fetoprotein, and human
      chorionic gonadotropin before and after surgical and pharmacologic treatment in
      patients with cystic echinococcosis (CE). METHODS: Serum samples were obtained
      from 40 CE patients (all with cysts in the liver) and from 10 sex- and age
      matched healthy donors (control group). Serum samples were drawn (1) before
      (presurgical group) and after (postsurgical group, including a 3-month cycle of
      albendazole) surgical and pharmacologic treatment. Serum tumor markers were
      measured, and indirect hemagglutination assay was performed. RESULTS: In 90% of
      confirmed cases of CE, indirect hemagglutination assay was positive. Mean (SD)
      serum CA19-9 concentrations for all patients in the presurgical and postsurgical
      groups were 45.1 +/- 30 kU/L and 17.02 +/- 11 kU/L, respectively. CA19-9
      concentrations were significantly greater in CE patients in the presurgical
      compared with the control group. Also, increased CA19-9 concentrations decreased
      significantly in the postsurgical compared with the presurgical group.
      CONCLUSIONS: A significant decrease in serum CA19-9 concentrations after surgical
      and pharmacologic therapy was demonstrated in the clinical follow-up of patients
      with CE (patients were tested 3 months after surgery). If our findings are
      confirmed and more-sensitive methods are developed for measuring serum CA19-9
      concentrations, new and interesting perspectives will be gained for the
      monitoring and treatment of patients with CE.

PMID- 18083136
TI  - Fournier's gangrene.
AB  - Fournier gangrene is a rare, but potentially devastating infection. A case is
      presented and the treatment principles are discussed.

PMID- 18083137
TI  - Results of laparoscopic anterior resection for rectal adenocarcinoma:
      retrospective analysis of 157 cases.
AB  - BACKGROUND: Laparoscopic excision of rectal tumors has gained favor in the last
      decade and several issues have reported encouraging results: still, the use of
      laparoscopy remains open to debate. The aim of the current study is to assess the
      reliability of laparoscopic anterior resection (LAR) for rectal cancer analyzing
      short-term outcomes and long-term survival. METHODS: The charts of 157 patients
      were reviewed retrospectively after anterior resection for rectal adenocarcinoma
      performed by minimal access. Patients undergoing emergency surgery were excluded.
      LAR was excluded in presence of preoperative features at computed tomography (CT)
      scan suggesting bulky tumors unresectable by laparoscopy or in case of
      anesthesiologic contraindications. Conversion rate and functional and oncologic
      outcomes were analyzed. Data on long-term results and survival were evaluated.
      RESULTS: LAR was performed in 157 patients, and conversion to laparotomy was
      required in 12 cases. Mean operation time for nonconverted patients was 229
      minutes (overall 238 minutes). Total mesorectal excision (TME) was performed in
      tumors of the mid and low rectum and a temporary ileostomy was performed in 56
      patients. The mean length of hospital stay (LOS) was 10.5 days. Morbidity of
      anterior resection included 17 anastomotic leaks after laparoscopic surgery (LS;
      5 in the converted patients). Conversion increased significantly the risk of leak
      (P < .005). Two leaks caused death. The mean number of nodes collected was 12.
      The incidence of local relapse was 4%, and the rate of anastomotic recurrence was
      nil. Survival probability with LS was .73 at 5 years. Patients in stage III took
      advantage of adjuvant treatment and had a better survival than patients in stage
      II (P = not significant [NS]). CONCLUSIONS: The outcomes of this study suggest
      that LAR for rectal cancer is a reliable procedure. Oncologic requirements were
      respected; parameters such as length of specimen, distal margin, and number of
      nodes retrieved were quite acceptable. Incidences of local recurrence and long
      term survival were comparable with those of other series.

PMID- 18083138
TI  - Clinicopathological features and medical management of early gastric cancer.
AB  - BACKGROUND: The detection of early gastric carcinoma (EGC) has increased
      worldwide due to advances in endoscopic techniques and equipment. The aim of the
      current study was to compare the clinicopathological findings of patients with
      and without lymph node metastasis. METHODS: A total of 440 cases of early gastric
      carcinoma in patients who underwent surgical procedures between 1981 and 2002 at
      Kochi Medical School were studied. RESULTS: Lymph node metastasis was observed in
      38 patients (8.6%) with EGC. Multivariate analysis identified 4 independent risk
      factors of lymph node metastasis: (1) submucosal invasion; (2) tumor diameter
      greater than 3.5 cm; (3) the presence of vascular invasion; and (4) the presence
      of lymphatic permeation. CONCLUSION: For patients with tumor size between 1 cm
      and 3.5 cm we would recommend endoscopic resection initially, with a
      consideration for additional surgical resection if microscopic vascular invasion
      or lymphatic permeation is demonstrated.

PMID- 18083139
TI  - Cell surface phosphorylation by a novel ecto-protein kinase: a key regulator of
      cellular functions in spermatozoa.
AB  - Since 1976 many studies have been reported on the occurrence and functional
      significance of ecto-protein kinases in a variety of cell types although their
      precise biochemical identity is largely unknown. This study reports for the first
      time purification to apparent homogeneity of an ecto-protein kinase (ecto-CIK)
      and some of its characteristics using caprine sperm as the cell model. The ecto
      CIK is a unique membrane-specific serine/threonine protein kinase. It is a
      strongly basic 115 kDa protein made up of two subunits: 63 and 55 kDa. The ecto
      kinase undergoes a remarkable lateral movement on the outer cell surface
      culminating in capping on the sperm acrosomal tip. MPS, its major protein
      substrate is also located on the acrosomal tip. Both ecto CIK and MPS serve as
      potential regulators of flagellar motility. This novel enzyme appears to be major
      kinase responsible for the reported regulation of mammalian cellular functions by
      modulating phosphorylation of the membrane-bound proteins.

PMID- 18083140
TI  - Human-mouse quantitative trait locus concordance and the dissection of a human
      neuroticism locus.
AB  - BACKGROUND: Exploiting synteny between mouse and human disease loci has been
      proposed as a cost-effective method for the identification of human
      susceptibility genes. Here we explore its utility in an analysis of a human
      personality trait, neuroticism, which can be modeled in mice by tests of
      emotionality. We investigated a mouse emotionality locus on chromosome 1 that
      contains no annotated genes but abuts four regulators of G protein signaling, one
      of which (rgs2) has been previously identified as a quantitative trait gene for
      emotionality. This locus is syntenic with a human region that has been
      consistently implicated in the genetic aetiology of neuroticism. METHODS: The
      functional candidacy of 29 murine sequence variants was tested by a combination
      of gel shift and transient transfection assays. Murine sequences that contained
      functional variants and exhibited significant cross-species conservation were
      prioritized for investigation in humans. Genetic association with neuroticism was
      tested in 1869 high and 2032 low unrelated individuals scored for neuroticism,
      selected from the extremes of 88,141 people from southwest England. RESULTS:
      Fifteen sequence variants contributed to variation in the expression of rgs18,
      the gene lying at the edge of the quantitative trait loci (QTL) interval. There
      was no evidence of association between neuroticism and single nucleotide
      polymorphisms (SNPs) lying in the human regions homologous to those of mouse
      functional variants. One SNP, rs6428058, in a region of sequence conservation 644
      kb upstream of RGS18, showed significant association (p = .000631). CONCLUSIONS:
      It is unlikely that a single variant is responsible for the mouse emotionality
      locus on chromosome 1. This level of underlying genetic complexity means that
      although cross-species QTL concordance may be invaluable for the identification
      of human disease loci, it is unlikely to be as informative in the identification
      of human disease-causing variants.

PMID- 18083141
TI  - Strain differences in the gating-disruptive effects of apomorphine: relationship
      to gene expression in nucleus accumbens signaling pathways.
AB  - BACKGROUND: Prepulse inhibition (PPI) of startle is a measure of sensorimotor
      gating that is deficient in certain psychiatric disorders, including
      schizophrenia. Sprague Dawley (SD) rats are more sensitive to PPI-disruptive
      effects of apomorphine (APO) at long interstimulus intervals (ISIs) (60-120 msec)
      and less sensitive to PPI-enhancing effects of APO at short ISIs (10-30 msec)
      compared with Long Evans (LE) rats. METHODS: Prepulse inhibition was tested in SD
      and LE rats after APO (.5 mg/kg) or vehicle in a within- subject design and
      sacrificed 14 days later. Total RNA was extracted from the nucleus accumbens
      (NAC). Approximately 700 dopamine-relevant transcripts on the Affymetrix 230 2.0
      microarray were analyzed. RESULTS: As previously reported, SD rats exhibited
      greater APO-induced PPI deficits at long intervals and less APO-induced PPI
      enhancement at short intervals compared with LE rats. One hundred four genes
      exhibited significantly different NAC expression levels in these two strains.
      Pathway analysis revealed that many of these genes contribute to dopamine
      receptor signaling, synaptic long-term potentiation, or inositol phosphate
      metabolism. The expression of some genes significantly correlated with measures
      of APO-induced PPI sensitivity in either SD or LE rats. The expression of select
      genes was validated by real-time reverse transcription polymerase chain reaction
      (RT-PCR). CONCLUSIONS: Differences in PPI APO sensitivity in SD versus LE rats
      are robust and reproducible and may be related to strain differences in the
      expression of genes that regulate signal transduction in the NAC. These genes
      could facilitate the identification of targets for ameliorating heritable gating
      deficits in brain disorders such as schizophrenia.

PMID- 18083142
TI  - Norepinephrine signaling through beta-adrenergic receptors is critical for
      expression of cocaine-induced anxiety.
AB  - BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding
      and aversive properties. While the mechanisms underlying cocaine's rewarding
      effects have been studied extensively, less attention has been paid to the
      unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In
      this study, we evaluated the performance of dopamine beta-hydroxylase knockout
      (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM)
      to examine the contribution of noradrenergic signaling to cocaine-induced
      anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like
      behavior in control (Dbh +/-) mice, as measured by a decrease in open arm
      exploration. The Dbh -/- mice had normal baseline performance in the EPM but were
      completely resistant to the anxiogenic effects of cocaine. Cocaine-induced
      anxiety was also attenuated in Dbh +/- mice following administration of
      disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using
      specific adrenergic antagonists, we found that pretreatment with the beta
      adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like
      behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist
      prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These
      results indicate that noradrenergic signaling via beta-adrenergic receptors is
      required for cocaine-induced anxiety in mice.

PMID- 18083143
TI  - Sensory-evoked gamma oscillations in chronic schizophrenia.
AB  - BACKGROUND: The early visual-evoked gamma oscillation (VGO) elicited by Gestalt
      stimuli is reduced in schizophrenia patients compared with healthy individuals,
      but it is unknown whether this effect is specific to these particular stimuli and
      task. In contrast, the early auditory-evoked gamma oscillation (AGO) was reported
      to be unaffected in a sample of unmedicated, mostly first-episode schizophrenics,
      but it is unknown whether this oscillation is abnormal in chronic, medicated
      patients. We investigated these issues by examining the VGO and AGO in chronic
      schizophrenic (SZ) and matched healthy control (HC) subjects. METHODS: Subjects
      (21 HC, 23 SZ) performed visual and auditory oddball tasks. Visual stimuli were
      letters, and auditory stimuli were simple tones. Event-related spectral measures
      (phase locking factor and evoked power) were computed on Morlet wavelet
      transformed single epochs from the standard trials. RESULTS: VGO phase locking at
      occipital electrodes was reduced in SZ compared with HC. In contrast, AGO phase
      locking and evoked power did not differ between groups. CONCLUSIONS: The VGO
      deficit may be a general phenomenon in schizophrenia, whereas the AGO evoked by
      simple tone stimuli does not appear to be abnormal in chronic, medicated
      schizophrenia patients.

PMID- 18083144
TI  - Neuroglobin protects PC12 cells against oxidative stress.
AB  - Neuroglobin (Ngb) is a newly discovered globin in the vertebrate brain that
      exhibits neuroprotection against hypoxic/ischemic injury. Hypoxic/ischemic brain
      injury is associated with accumulation of reactive oxygen species (ROS) and/or
      reactive nitrogen species (RNS), and antioxidants or ROS scavengers promote cell
      survival. Therefore, Ngb may serve as a scavenger of toxic reactive species, such
      as hydrogen peroxide. To examine the anti-oxidative role of neuroglobin, PC12
      cells were transfected with wild type and mutant (H64 V/H96A) Ngb for 48 h and
      then treated with H2O2 (0.1, 0.2 and 0.4 mM) for 6 h. Ngb siRNA decreased the
      H2O2-induced Ngb expression and exacerbated H2O2-induced cell injury. Transient
      transfection of Ngb induced dose-dependent increases in Ngb protein expression
      and did not alter SOD, GPX, and catalase activities. Overexpression of wild type
      Ngb, but not of mutant Ngb, significantly attenuated H2O2-induced ROS/RNS
      accumulation and lipid peroxidation, decreased H2O2-induced mitochondrial
      dysfunction and apoptosis, and promoted overall cell survival. Thus, Ngb plays a
      protective role against oxidative stress, which appears to be primarily mediated
      by intrinsic Ngb antioxidant properties.

PMID- 18083145
TI  - Metallothionein I,II deficient mice do not exhibit significantly worse long-term
      behavioral outcomes following neonatal hypoxia-ischemia: MT-I,II deficient mice
      have inherent behavioral impairments.
AB  - Metallothionein I and II are small metal binding proteins with a high affinity
      for zinc. They are found in the CNS and are thought to play a role in modulating
      the effects of free zinc. We hypothesized that MT-I,II deficient mice would have
      more neurological deficits both functionally and anatomically following a
      neonatal hypoxic-ischemic (HI) insult than wild-type mice subjected to the same
      insult. Forty wild-type and 40 MT-I,II deficient C57 X 129T2 F1 P10 mice were
      randomized to either 45 min of HI or sham HI. Beginning on P50, the mice were
      given a series of behavioral tests including locomotor activity, novel object
      recognition, Morris water maze (cued, hidden platform, reduced platform), a 2
      week-delayed probe trial and an apomorphine-induced rotation test. At the
      conclusion of testing, the brains were removed for histological analysis
      including staining with NeuN and GFAP to assess neuronal loss and reactive
      gliosis. There were no significant differences in functional or anatomic measures
      between the wild-type HI mice and the MT-I,II deficient HI mice. The MT-I,II
      deficient mice exhibited an impaired rate of learning in the spatially oriented
      mazes but once learned retained the information as well as the wild-type mice.
      The absence of functional MT-I,II proteins does not result in significantly worse
      injury following 45 min of HI on P10. The MT-I,II deficient mice have baseline
      impairments in spatial learning but not retention.

PMID- 18083147
TI  - Short term memory for tactile stimuli.
AB  - Research has shown that unreported information stored in rapidly decaying visual
      representations may be accessed more accurately using partial report than using
      full report procedures (e.g., [Sperling, G., 1960. The information available in
      brief visual presentations. Psychological Monographs, 74, 1-29.]). In the 3
      experiments reported here, we investigated whether unreported information
      regarding the actual number of tactile stimuli presented in parallel across the
      body surface can be accessed using a partial report procedure. In Experiment 1,
      participants had to report the total number of stimuli in a tactile display
      composed of up to 6 stimuli presented across their body (numerosity task), or
      else to detect whether or not a tactile stimulus had previously been presented in
      a position indicated by a visual probe given at a variable delay after offset of
      a tactile display (i.e., partial report). The results showed that participants
      correctly reported up to 3 stimuli in the numerosity judgment task, but their
      performance was significantly better than chance when up to 5 stimuli were
      presented in the partial report task. This result shows that short-lasting
      tactile representations can be accessed using partial report procedures similar
      to those used previously in visual studies. Experiment 2 showed that the duration
      of these representations (or the time available to consciously access them)
      depends on the number of stimuli presented in the display (the greater the number
      of stimuli that are presented, the faster their representation decays). Finally,
      the results of a third experiment showed that the differences in performance
      between the numerosity judgment and partial report tasks could not be explained
      solely in terms of any difference in task difficulty.

PMID- 18083146
TI  - Effects of chronic hypoxia in developing rats on dendritic morphology of the CA1
      subarea of the hippocampus and on fear-potentiated startle.
AB  - Chronic hypoxia (CH) present in infants with cyanotic congenital heart disease
      may be responsible for subsequent cognitive deficits seen in these children. In a
      rat model of CH [10% O(2) between postnatal day (P) 3 and 28], we have
      demonstrated significant alterations in energy metabolism and excitatory
      neurotransmission in the developing hippocampus. These alterations may adversely
      affect dendritic morphology, which is a highly energy-dependent and excitatory
      neurotransmitter-mediated event, and hippocampus-mediated behaviors. We measured
      the apical segment length of dendrites in pyramidal neurons of the CA1 region of
      the hippocampus using microtubule-associated protein-2 (MAP-2) histochemistry on
      P28 while the animals were hypoxic (n=8 in CH and n=6 in control), and on P56
      after the animals had been normoxic for 4 weeks (n=8/group). We also compared
      dorsal hippocampus-dependent trace fear conditioning and dorsal hippocampus
      independent delay fear conditioning on P56. Developmental trajectory of the
      apical segment length was similar in CH and controls, decreasing between P28 and
      P56. However, when compared with the controls, the apical segment length was
      longer in the CH group on both P28 [55.11+/-2.30 microm (CH) vs. 40.52+/-1.20
      microm (control), p<0.001] and P56 [44.01+/-1.56 microm (CH) vs. 31.75+/-1.31
      microm (control), p<0.001], suggesting the persistence of an immature dendritic
      architecture. Both trace and delay fear conditioning were decreased in the CH
      group, suggesting functional abnormality beyond the dorsal hippocampus. These
      structural and functional alterations may contribute to the cognitive deficits
      seen in infants at risk for CH.

PMID- 18083148
TI  - Antagonizing beta-amyloid peptide neurotoxicity of the anti-aging fungus
      Ganoderma lucidum.
AB  - Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi) is a medicinal fungus used
      clinically in many Asian countries to promote health and longevity. Synaptic
      degeneration is another key mode of neurodegeneration in Alzheimer's disease
      (AD). Recent studies have shown the loss of synaptic density proteins in each
      individual neuron during the progression of AD. It was recently reported that
      beta-amyloid (Abeta) could cause synaptic dysfunction and contribute to AD
      pathology. In this study, we reported that aqueous extract of G. lucidum
      significantly attenuated Abeta-induced synaptotoxicity by preserving the synaptic
      density protein, synaptophysin. In addition, G. lucidum aqueous extract
      antagonized Abeta-triggered DEVD cleavage activities in a dose-dependent manner.
      Further studies elucidated that phosphorylation of c-Jun N-terminal kinase, c
      Jun, and p38 MAP kinase was attenuated by G. lucidum in Abeta-stressed neurons.
      Taken together, the results prove a hypothesis that anti-aging G. lucidum can
      prevent harmful effects of the exterminating toxin Abeta in AD.

PMID- 18083149
TI  - Chronic morphine exposure during puberty induces long-lasting changes in opioid
      related mRNA expression in the mediobasal hypothalamus.
AB  - Substance abuse in developing females may have significant long-term effects on
      reproductive competency. Chronic morphine exposure during puberty has been shown
      to reduce prolactin secretion in lactating rats. Opioid activity within the
      mediobasal hypothalamus (MBH) regulates suckling-induced prolactin secretion.
      Thus, the current study was conducted to determine whether chronic pubertal
      morphine exposure alters the expression of mu- and/or kappa-opioid receptor mRNA
      or pro-opioimelanocortin (POMC) mRNA within the MBH. Using an increasing dose
      regimen, female Sprague-Dawley rats were injected twice daily for a total of 20
      days with morphine sulfate or saline beginning at 30 days of age. Several weeks
      later, quantitative RT-PCR was used to determine mRNA expression within the MBH
      in diestrus, never pregnant (nulliparous) controls, postpartum day 5 (PPD5),
      PPD10, PPD18, and diestrus, reproductively experienced (primiparous) females.
      Pubertal morphine exposed females had increased mu- and kappa-receptor mRNA
      expression as well as decreased POMC mRNA expression on diestrus. During
      lactation, mu- and kappa-receptor mRNA expression in the MBH decreased while POMC
      mRNA expression increased in similarly treated females. No changes in mRNA
      expression were observed during lactation in pubertal saline-treated females;
      however, increased mu- and kappa-receptor mRNA expression as well as decreased
      POMC mRNA expression was observed in primiparous, pubertal saline-treated females
      when compared to nulliparous controls. Thus, chronic morphine exposure during
      puberty results in long-term alterations in mu- and kappa-receptor as well as
      POMC mRNA expression in the MBH which are similar to the changes observed
      following reproductive experience. These changes do not correlate with the
      decreased prolactin secretion observed during early lactation; however, they do
      demonstrate the enduring nature of the effects of chronic opiate exposure during
      puberty on hypothalamic opioid systems in adulthood.

PMID- 18083150
TI  - Increased levels of carbonic anhydrase II in the developing Down syndrome brain.
AB  - By using a proteomic approach, we found increased levels of carbonic anhydrase II
      (CA II) in the brain of Ts65Dn mice, a mouse model for Down syndrome (DS).
      Further immunoblot analyses showed that the levels of CA II are increased not
      only in the brain of adult Ts65Dn mice but also in the brain of infants and young
      children with DS. Cellular localization of the enzyme in human brain,
      predominantly in the oligodendroglia and primitive vessels in fetal brain and in
      the oligodendroglia and some GABAergic neurons postnatally, was similar in DS
      subjects and controls. Given the role of CA II in regulation of electrolyte and
      water balance and pH homeostasis, up-regulation of CA II may reflect a
      compensatory mechanism mobilized in response to structural/functional
      abnormalities in the developing DS brain. However, this up-regulation may also
      have an unfavorable effect by increasing susceptibility to seizures of children
      with DS.

PMID- 18083152
TI  - A basidiomycetous yeast, Pseudozyma tsukubaensis, efficiently produces a novel
      glycolipid biosurfactant. The identification of a new diastereomer of
      mannosylerythritol lipid-B.
AB  - Mannosylerythritol lipids (MELs) are glycolipid biosurfactants produced by the
      yeast strains of the genus Pseudozyma. These compounds show not only excellent
      surface-active properties but also versatile biochemical activities. In the
      course of MEL production by Pseudozyma tsukubaensis, we found an unusual MEL that
      had a different carbohydrate structure from that of conventional MELs. The
      carbohydrate structure was identified as 1-O-beta-D-mannopyranosyl-D-erythritol,
      and the MEL was confirmed to be 1-O-beta-(2',3'-di-O-alka(e)noyl-6'-O-acetyl-D
      mannopyranosyl)-D-erythritol. Interestingly, the configuration of the erythritol
      moiety in the present MEL was opposite to that of the known MEL-B, 4-O-beta
      (2',3'-di-O-alka(e)noyl-6'-O-acetyl-D-mannopyranosyl)-D-erythritol, and to that
      of all MELs hitherto reported. The present MEL should thus provide different
      interfacial and biochemical properties compared to conventional MELs.

PMID- 18083151
TI  - Synthesis of acyl thiourea derivatives of chitosan and their antimicrobial
      activities in vitro.
AB  - Three different acyl thiourea derivatives of chitosan (CS) were synthesized and
      their structures were characterized by FT-IR spectroscopy and elemental analysis.
      The antimicrobial behaviors of CS and its derivatives against four species of
      bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and
      Sarcina) and four crop-threatening pathogenic fungi (Alternaria solani, Fusarium
      oxysporum f. sp. vasinfectum, Colletotrichum gloeosporioides (Penz.) Saec, and
      Phyllisticta zingiberi) were investigated. The results indicated that the
      antimicrobial activities of the acyl thiourea derivatives are much better than
      that of the parent CS. The minimum value of MIC and MBC of the derivatives
      against E. coli was 15.62 and 62.49 microg/mL, respectively. All of the acyl
      thiourea derivatives had a significant inhibitory effect on the fungi in
      concentrations of 50-500 microg/mL; the maximum inhibitory index was 66.67%. The
      antifungal activities of the chloracetyl thiourea derivatives of CS are
      noticeably higher than the acetyl and benzoyl thiourea derivatives. The degree of
      grafting of the acyl thiourea group in the derivatives was related to antifungal
      activity; higher substitution resulted in stronger antifungal activity.

PMID- 18083153
TI  - Efficient synthesis of spacer-N-linked double-headed glycosides carrying N
      acetylglucosamine and N,N'-diacetylchitobiose and their cross-linking activities
      with wheat germ agglutinin.
AB  - We describe here an efficient synthetic route to spacer-N-linked double-headed
      glycosides via a simple two-step procedure. N-Acetylglucosamine (GlcNAc) and N,N'
      diacetylchitobiose [(GlcNAc)(2)] were treated with ammonia and the resulting N
      beta-glycosylamines were coupled to a series of dicarboxylic acids. Condensation
      with each dicarboxylic acid proceeded stereoselectively to give the corresponding
      beta-N-linked double-headed glycoside without the need for any
      protection/deprotection steps. Interaction of the resulting N-linked double
      headed glycosides with wheat germ agglutinin (WGA) were then investigated using a
      precipitation assay and an optical biosensor based on surface plasmon resonance
      (SPR). Spacer-N-linked double-headed glycosides bearing GlcNAc and (GlcNAc)(2)
      were found to be capable of binding and precipitating WGA as divalent ligands.
      However, the length of the spacer groups between the two terminal sugar residues
      was found to greatly influence the cross-linking activities with the lectin.

PMID- 18083154
TI  - Effects of cooling treatment and glutaraldehyde on the morphology of Au
      nanostructures synthesized from chitosan.
AB  - A facile approach for the synthesis of chitosan-based Au nanostructures that have
      interesting absorptions in the near-infrared (NIR) region is presented. The
      effects of cooling treatment and the cross-linking agent glutaraldehyde on the
      formation of Au nanostructures based on chitosan were investigated. It has been
      demonstrated that the size and shape, and thus the optical properties of Au
      nanostructures, could be modulated via cooling treatment. The optical absorption
      extension of these Au nanostructures in the NIR region is promising in biomedical
      applications. The presence of a cross-linking agent, glutaraldehyde, during
      synthesis accelerated the reduction of the Au precursor and favored the growth of
      isotropic Au nanoparticles. A possible mechanism for the change in growth
      modality of Au nanostructures with and without glutaraldehyde was elucidated.

PMID- 18083155
TI  - Ordered short-term memory differs in signers and speakers: implications for
      models of short-term memory.
AB  - Capacity limits in linguistic short-term memory (STM) are typically measured with
      forward span tasks in which participants are asked to recall lists of words in
      the order presented. Using such tasks, native signers of American Sign Language
      (ASL) exhibit smaller spans than native speakers ([Boutla, M., Supalla, T.,
      Newport, E. L., & Bavelier, D. (2004). Short-term memory span: Insights from sign
      language. Nature Neuroscience, 7(9), 997-1002]). Here, we test the hypothesis
      that this population difference reflects differences in the way speakers and
      signers maintain temporal order information in short-term memory. We show that
      native signers differ from speakers on measures of short-term memory that require
      maintenance of temporal order of the tested materials, but not on those in which
      temporal order is not required. In addition, we show that, in a recall task with
      free order, bilingual subjects are more likely to recall in temporal order when
      using English than ASL. We conclude that speakers and signers do share common
      short-term memory processes. However, whereas short-term memory for spoken
      English is predominantly organized in terms of temporal order, we argue that this
      dimension does not play as great a role in signers' short-term memory. Other
      factors that may affect STM processes in signers are discussed.

PMID- 18083157
TI  - One or two dimensions in spontaneous classification: a simplicity approach.
AB  - When participants are asked to spontaneously categorize a set of items, they
      typically produce unidimensional classifications, i.e., categorize the items on
      the basis of only one of their dimensions of variation. We examine whether it is
      possible to predict unidimensional vs. two-dimensional classification on the
      basis of the abstract stimulus structure, by employing Pothos and Chater's
      simplicity model of spontaneous categorization [Pothos, E. M., & Chater, N.
      (2002). A simplicity principle in unsupervised human categorization. Cognitive
      Science, 26, 303-343]. The simplicity model provides a quantitative measure of
      how intuitive a particular classification is. With objects represented in two
      dimensions, we propose that a unidimensional classification will be preferred if
      it is more intuitive than all possible two-dimensional ones, and vice versa.
      Empirical results supporting this proposal are reported. Implications for
      Goodman's paradox are discussed.

PMID- 18083156
TI  - Children's developing notions of (im)partiality.
AB  - This research examines the development of children's understanding that people's
      judgments may be skewed by relationships, and that situational factors may make
      it difficult to be impartial. One hundred and seventy-one adults and children
      between kindergarten and eighth grade heard stories about judges in contests with
      objective or subjective criteria for winning. In Experiment 1, by fourth grade,
      children rated a judge with no personal connection (the "neutral judge") as being
      more likely to be objective than a judge with a personal connection (the
      "connected judge"). Younger children showed the opposite pattern. Experiment 2
      replicated this finding for judges, and also found that children across
      development have similar ideas regarding the characteristics for being a good
      judge. Not until eighth grade, however, did children indicate that a connected
      judge was more problematic in subjective situations than in objective ones.

PMID- 18083158
TI  - Establishment of cell fate during early Drosophila embryogenesis requires
      transcriptional Mediator subunit dMED31.
AB  - During early Drosophila embryogenesis, formation of the anterior-posterior (A/P)
      axis depends on spatial gradients of maternal morphogens. It is well recognized
      that positional information is transmitted from these morphogens to the gap
      genes. However, how this information is being transmitted is largely unknown. The
      transcriptional Mediator complex is involved in the fine tuning of the signaling
      between chromatin status, transcription factors and the RNA polymerase II
      transcription machinery. We found that a mutation in the conserved subunit of the
      Mediator complex, dMED31, hampers embryogenesis prior to gastrulation and leads
      to aberrant expression of the gap genes knirps and Kruppel and the pair-rule
      genes fusi tarazu and even-skipped along the A/P axis. Expression of the maternal
      morphogens dorsal and hunchback was not affected in dMED31 mutants. mRNA
      expression of dMED31 exactly peaks between the highest expression levels of the
      maternal genes and the gap genes. Together, our results point to a role for
      dMED31 in guiding maternal morphogen directed zygotic gap gene expression and
      provide the first in vivo evidence for a role of the Mediator complex in the
      establishment of cell fate during the cellular blastoderm stage of Drosophila
      melanogaster.

PMID- 18083160
TI  - Dynamic expression of Lrp2 pathway members reveals progressive epithelial
      differentiation of primitive endoderm in mouse blastocyst.
AB  - Mesenchyme to epithelium transitions are crucial to embryonic development. The
      early mouse embryo offers an excellent model to study epithelium formation as
      during the first three days of development two epithelia are formed, the
      trophectoderm (TE) and the primitive endoderm (PrE). We have previously shown
      that PrE cells are determined within the blastocyst ICM long before epithelium
      formation. In this work, we isolated Lrp2 as a novel PrE precursor (pre-PrE)
      marker by using a microarray strategy that combines a transcriptome analysis of
      three stem cell lines and early embryos. A detailed expression analysis shows
      that Lrp2 expression is induced in late E3.5 embryos indicating that pre-PrE
      cells are progressively maturing prior to polarization into an epithelium.
      Furthermore, the subcellular location of Lrp2, Disabled-2 (Dab2) and Collagen-IV
      shows that the epithelial structure is acquired in individual cells through
      successive steps.

PMID- 18083159
TI  - Direct control of the proneural gene atonal by retinal determination factors
      during Drosophila eye development.
AB  - The determination of neuronal identity in Drosophila cells depends on the
      accurate expression of proneural genes. The proneural gene atonal (ato) encodes a
      basic-HLH protein required for photoreceptor and chordotonal organ formation. The
      initial expression of ato in imaginal discs is regulated by sequences that lie 3'
      to its open reading frame. In this report, we show that the initial ato
      transcription in different imaginal discs is regulated by distinct 3' cis
      regulatory sequences. The eye-specific ato 3' cis-regulatory sequence consists of
      two distinct elements we term 2.8 PB and 3.6 BP that regulate ato transcription
      during different stages of eye development. The 2.8 PB enhancer contains a highly
      conserved consensus binding site for the retinal determination (RD) factor Sine
      oculis (So). Mutation of this So binding site abolishes 2.8 PB enhancer activity.
      Furthermore the RD factors So and Eyes absent (Eya) are required for 2.8 PB
      enhancer activity and can induce ectopic 2.8 PB reporter expression. In contrast,
      ectopic Dpp signaling is not sufficient to induce ato 3' enhancer activation but
      can induce increased levels of RD factor Dachshund (Dac) and synergize with So
      and Eya to increase ato 3' enhancer activity. These results demonstrate a direct
      mechanism by which the RD factors regulate ato expression and suggest an
      important role of Dpp in the activation of ato 3' enhancer is to regulate the
      levels of RD factors.

PMID- 18083161
TI  - Berberine inhibits RANKL-induced osteoclast formation and survival through
      suppressing the NF-kappaB and Akt pathways.
AB  - Berberine, an isoquinoline alkaloid isolated from several medicinal plants, has
      been reported to possess anti-bacterial, anti-inflammatory and antitumor
      properties. Although berberine also inhibits osteoclastogenesis and bone
      resorption, the molecular machinery for its inhibitory effects remains unknown.
      This study focused on the suppressive effects of berberine on receptor activator
      of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-induced osteoclastogenesis
      and survival. Berberine inhibited RANKL-mediated osteoclast formation and
      survival while having no cytotoxic effects on bone marrow macrophages or
      osteoblastic cells. Berberine attenuated RANKL-induced activation of NF-kappaB
      through inhibiting phosphorylation at the activation loop of IkappaBalpha kinase
      beta, phosphorylation and degradation of IkappaBalpha, and NF-kappaB p65 nuclear
      translocation. RANKL-induced Akt phosphorylation was strongly inhibited by
      berberine; however, neither monocyte/macrophage-colony stimulating factor (M-CSF)
      induced nor insulin-induced Akt activation was inhibited by the drug. Under M-CSF
      and RANKL-deprived condition, berberine increased the active form of caspase-3
      in osteoclasts. By contrast, berberine did not potentiate the activation of
      caspase-3 in M-CSF-deprived bone marrow macrophages. These findings indicate that
      berberine inhibits osteoclast formation and survival through suppression of NF
      kappaB and Akt activation and that both pathways in the osteoclast lineage are
      highly sensitive to berberine treatment.

PMID- 18083162
TI  - Mechanisms underlying the nociceptive and inflammatory responses induced by
      trypsin in the mouse paw.
AB  - It has been demonstrated that trypsin is able to evoke the classical signals of
      inflammation, mainly via the activation of proteinase-activated receptor-2 (PAR
      2). This study was designed to evaluate the inflammatory and nociceptive
      responses caused by trypsin injection in the mouse paw. Trypsin produced a dose-
      and time-related paw edema, a response that was markedly reduced in PAR-2
      deficient mice compared to wild-type mice, particularly at the early time-points
      after trypsin injection. In addition, trypsin produced an increase in
      myeloperoxidase (MPO) activity, which was significantly reduced in PAR-2
      deficient mice. The injection of trypsin into the mouse paw also elicited a dose-
      and time-dependent spontaneous nociception, as well as thermal and mechanical
      hypernociceptive responses, which were consistently decreased in mice with
      genetic deletion of PAR-2. Pharmacological evaluation revealed that edema
      formation and spontaneous nociception caused by trypsin injection in the mouse
      paw are mediated by a complex range of mediators. Both edema and nociception seem
      to rely on the production of neuropeptides, probably involving C-fibre activation
      and vanilloid receptor-1 (TRPV1), besides the stimulation of kinin B(2)
      receptors. Edematogenic response is also likely related to the production of
      cyclooxygenase (COX) metabolites, whereas the mast cell activation appears to be
      greatly associated to spontaneous nociception. Altogether, the present results
      indicate that trypsin-induced edema and nociception in the mouse paw represent
      multi-mediated responses that are largely, but not exclusively, related to the
      activation of PAR-2. These pieces of evidence provide new insights on the role of
      trypsin in pain and inflammation.

PMID- 18083163
TI  - A comparison of the tube forming potentials of early and late endothelial
      progenitor cells.
AB  - The identification of circulating endothelial progenitor cells (EPCs) has
      revolutionized approaches to cell-based therapy for injured and ischemic tissues.
      However, the mechanisms by which EPCs promote the formation of new vessels remain
      unclear. In this study, we obtained early EPCs from human peripheral blood and
      late EPCs from umbilical cord blood. Human umbilical vascular endothelial cells
      (HUVECs) were also used. Cells were evaluated for their tube-forming potential
      using our novel in vitro assay system. Cells were seeded linearly along a 60 mum
      wide path generated by photolithographic methods. After cells had established a
      linear pattern on the substrate, they were transferred onto Matrigel. Late EPCs
      formed tubular structures similar to those of HUVECs, whereas early EPCs randomly
      migrated and failed to form tubular structures. Moreover, late EPCs participate
      in tubule formation with HUVECs. Interestingly, late EPCs in Matrigel migrated
      toward pre-existing tubular structures constructed by HUVECs, after which they
      were incorporated into the tubules. In contrast, early EPCs promote sprouting of
      HUVECs from tubular structures. The phenomena were also observed in the in vivo
      model. These observations suggest that early EPCs cause the disorganization of
      pre-existing vessels, whereas late EPCs constitute and orchestrate vascular tube
      formation.

PMID- 18083164
TI  - Dose dependent cataractogenesis and Maximum Tolerable Dose (MTD(2.3:16)) for UVR
      300 nm-induced cataract in C57BL/6J mice.
AB  - The purpose of the present study was to investigate the in vivo dose response
      function for UVR 300 nm-induced cataract in the C57BL/6J mouse lens and to
      establish a cataract threshold estimate expressed as Maximum Tolerable Dose
      (MTD(2.3:16)) for UVR 300 nm-induced cataract in the C57BL/6J mouse lens.
      Knowledge of the MTD(2.3:16) in the C57BL/6J mouse will permit quantitative in
      vivo comparison of UVR-B threshold sensitivity of knockout mice, e.g. animals
      deficient in key antioxidative enzymes or mice suffering from genetically
      predetermined eye disease, to wild type animals. Eighty C57BL/6J mice were
      divided into four dose groups. The animals were exposed unilaterally to 0, 2, 4,
      or 8 kJ/m(2) UVR 300 nm for 15 min (n=20). The radiation output of the UVR-source
      had lambda(max) at 302.6 nm with 5 nm full width at half maximum. Two days after
      exposure cataract was quantified as forward lens light scattering intensity in
      the exposed and the contralateral non-exposed lens. Morphological lens changes
      were documented using grid and dark field illumination photography. MTD(2.3:16)
      was estimated from the forward light scattering measurements. Two days after
      exposure mainly anterior subcapsular but also cortical and nuclear cataract
      developed in lenses that had received 2, 4, and 8 kJ/m(2) UVR 300 nm. Forward
      light scattering intensity increased with increasing UVR 300 nm dose. MTD(2.3:16)
      for the mouse lens was estimated to 2.9 kJ/m(2) UVR 300 nm. Lens light scattering
      intensity in the C57BL/6J mouse lens increases with UVR 300 nm in vivo dose in
      the range 0-8 kJ/m(2). The MTD(2.3:16) of 2.9 kJ/m(2) in the C57BL/6J mouse lens
      determined here, is essential to quantify and compare in vivo the impact of
      genetic modulation on lens susceptibility to oxidative stress and plan dose
      ranges in future investigations of UVR 300 nm-induced cataract pathogenesis.

PMID- 18083165
TI  - Entamoeba histolytica: cyst-like structures in vitro induction.
AB  - The cyst of Entamoeba histolytica is responsible for amebiasis infection.
      However, no axenic in vitro system exists that promotes mass encystation for
      studying this process of this human-infecting parasite. Cyst-like structures of
      E. histolytica obtained in this work were induced using TYI-S-33 media in
      combination with enterobacterias Escherichia coli and Enterococcus faecalis
      conditioned media, high CO2 tension and histamine. Cyst-like structures showed
      the same characteristics of a typical E. histolytica cyst: aggregation,
      resistance to 0.15% sarcosyl for 10 min, high signal of fluorescence under UV
      light when stained with 10% calcofluor M2r and the surface topology showed a
      wrinkled wall. In addition these structures are multinucleated with condensed
      chromatin attached to nuclear membrane, contain big vacuoles and
      ribonucleoproteic helices in the cytoplasm and also present a thin cell wall.
      Last all characteristics are all the same as a typical of E. histolytica cyst.

PMID- 18083166
TI  - Giardia duodenalis: pathological alterations in gerbils, Meriones unguiculatus,
      infected with different dosages of trophozoites.
AB  - To examine the infection kinetics and development of alterations in the small
      intestine of gerbils (Meriones unguiculatus), 72 gerbils were divided into six
      groups (A to F), with A serving as control and the others inoculated with
      increasing doses of trophozoites from Giardia duodenalis human isolate. The
      infection kinetics and the development of histopathological alterations were
      monitored by optical scanning electron microscopy (SEM). A 12-day prepatent
      period was observed, with intermittent elimination up to day 35 after
      inoculation. Statistically significant differences were found between the mean
      number of trophozoites recovered, per group, on the days of sacrifice, and a
      positive correlation between the inoculum dosage and the number of trophozoites
      recovered. Morphometrically, the villus:crypt ratio showed a drop in all the
      groups when compared with the control group. SEM revealed an increase in mucus
      production in the inoculated animals and the presence of trophozoite clusters at
      the top and base of the villi. The dosage of trophozoite inoculum does not
      interfere in the ability for infection to occur or in the development of
      histopathological alterations generated by intestinal colonization.

PMID- 18083167
TI  - A survey of preferences and practices of endometrial ablation/resection for
      menorrhagia in the United Kingdom.
AB  - OBJECTIVE: To survey the preferences and variations in the current use of first-
      and second-generation endometrial ablative techniques for menorrhagia among the
      consultant gynecologists in the United Kingdom, given the call for further
      studies to systematically compare the clinical effectiveness of the various
      endometrial ablation techniques. DESIGN: Postal questionnaire survey. POPULATION:
      One thousand, four hundred sixty consultant gynecologists in the United Kingdom.
      MAIN OUTCOME MEASURE(S): Preferred endometrial ablation/resection method and
      variations in the current practices. RESULT(S): Six hundred ten (41%) consultants
      responded. Of these, 449 (73%) performed endometrial ablation/resection. Thermal
      balloon ablation (32.1%) was the preferred method, followed by microwave
      endometrial ablation (29.8%), transcervical resection of the endometrial alone or
      combined with roller ball diathermy (18.5%), Novasure (9.8%), hydrotherm ablation
      (6.9%), roller ball (2%), and laser (0.9%). Patient response to treatment was
      assessed using clinical history (64.3%), menstrual calendar (7.6%), clinical
      history and menstrual calendar (21.3%), questionnaires (5.8%), and pictorial
      blood loss assessment charts (0.4%). A total of 52.2% used gonadotrophin
      releasing hormone analogues preoperatively. Variations in techniques for
      transcervical resection of the endometrial included methods used to treat the
      uterine fundus and cornuae, fluid management, and operating pressures.
      CONCLUSION(S): Second-generation endometrial ablation devices were preferred to
      first-generation devices for the management of menorrhagia. Thermal balloon
      ablation was the most preferred method. However, variations in surgical practices
      will make assessment of clinical efficacy a challenge.

PMID- 18083168
TI  - Empty follicle syndrome in the setting of dramatic weight loss after bariatric
      surgery: case report and review of available literature.
AB  - OBJECTIVE: To describe empty follicle syndrome, potentially due to route of human
      chorionic gonadotropin (hCG) administration, in a patient who had previously
      undergone bariatric surgery. DESIGN: Case report and review of literature.
      SETTING: Academic medical center. PATIENT(S): A 42-year-old nulliparous, morbidly
      obese woman who had presented for assisted reproduction treatment after having
      lost 175 pounds via gastric bypass surgery, resulting in abdominal skin
      redundancy. INTERVENTION(S): The patient's gastric bypass surgery had resulted in
      abdominal skin redundancy. In her first cycle, recombinant hCG was used with a
      luteal gonadotropin-releasing hormone (GnRH) agonist/recombinant follicle
      stimulation hormone (FSH) protocol. At hCG administration, her estradiol level
      was 2342 pg/mL, and 18 follicles were measured. At retrieval, no oocytes were
      recovered, and her serum hCG level was 19 mIU/mL. In the subsequent cycle,
      identical ovarian stimulation was performed, with peak estradiol of 2891 pg/mL,
      but intramuscular hCG was administered. At retrieval, her serum hCG level was 45
      mIU/mL, and 19 oocytes were recovered, resulting in 10 embryos. Five embryos were
      transferred, and a singleton pregnancy resulted. MAIN OUTCOME MEASURE(S):
      Recovery of oocytes. RESULT(S): Clinical pregnancy. CONCLUSION(S): Abdominal skin
      redundancy after bariatric surgery may alter the absorption of subcutaneously
      administered infertility medications. Additional studies are needed to treat
      infertile patients optimally after weight-reduction surgery.

PMID- 18083169
TI  - Effect of letrozole at 2.5 mg or 5.0 mg/day on ovarian stimulation with
      gonadotropins in women undergoing intrauterine insemination.
AB  - OBJECTIVE: To determine the effect of combined therapy of letrozole (2.5 mg or
      5.0 mg) with recombinant follicle-stimulating hormone (FSH) in comparison with
      the administration of recombinant FSH alone in an intrauterine insemination (IUI)
      program. DESIGN: Retrospective study. SETTING: Assisted fertilization program in
      a specialized infertility center. PATIENT(S): 110 women undergoing IUI and
      gonadotropin therapy. INTERVENTION(S): Recombinant FSH alone administered from
      day 3 or combined with letrozole, 2.5 or 5.0 mg/day, on days 3 to 7, and
      gonadotropins starting on day 7 of the menstrual cycle. Transvaginal ultrasound
      examinations were done until the dominant follicle reached 18 mm in diameter.
      Ovulation was triggered with 10,000 IU of human chorionic gonadotropin (hCG), and
      IUI performed 30 to 40 hours later. MAIN OUTCOME MEASURE(S): Recombinant FSH dose
      required, number of follicles greater than 14 mm and 18 mm, endometrial
      thickness, pregnancy rates, miscarriages, and characteristics of newborns.
      RESULT(S): Women treated with FSH and 5.0 mg/day of letrozole required a lower
      dose of FSH than the group cotreated with 2.5 mg/day of letrozole or with FSH
      alone. Throughout most of the follicular phase, the endometrial thickness was
      statistically significantly less in both letrozole cotreatment groups compared
      with the FSH control group. By the day of hCG administration, the endometrial
      thickness was comparable among all the groups. The pregnancy rates were the same
      with recombinant FSH alone or combined with letrozole. CONCLUSION(S): In terms of
      cost-effectiveness, 5.0 mg/day of letrozole is more effective than the 2.5 mg/day
      in cotreatment with no adverse effect on pregnancy rate or outcome.

PMID- 18083170
TI  - Non-Hodgkin's lymphoma survivors' fertility and sexual function-related
      information needs.
AB  - This population-based study assessed information needs related to fertility and
      sexual function in 250 non-Hodgkin's lymphoma survivors from a Los Angeles
      Surveillance, Epidemiology, and End Results cancer registry 2-5 years after
      diagnosis. Results suggest that many survivors have persistent fertility and
      sexual concerns 2-5 years after diagnosis, highlighting the importance of
      oncologists working collaboratively with reproductive endocrinologists to
      uniformly inform patients about these issues during routine follow-up cancer care
      visits.

PMID- 18083172
TI  - The autopsy as a quality indicator in trauma care: has it had its day?

PMID- 18083171
TI  - Successful pregnancy following double-frozen embryo transfer in a patient with
      repeated implantation failure.
AB  - OBJECTIVE: To report a case of successful singleton pregnancy following a novel
      technique of sequential double transfer of two groups of frozen embryos at the
      same developmental stage (8-cell) at 5 and 7 days after the LH surge to a patient
      with seven previous failed assisted reproductive technology (ART) cycles. DESIGN:
      Case report. SETTING: University of Toronto affiliated infertility clinic.
      PATIENT: A 27-year-old female with a three-year history of primary infertility.
      INTERVENTION: Double frozen embryo transfer of day-3 embryos two days apart in
      the luteal phase. MAIN OUTCOME MEASURE(S): Successful pregnancy. RESULT(S):
      Successful singleton pregnancy resulting in the delivery of healthy baby boy.
      CONCLUSION: To the best of our knowledge, the patient is the first to be treated
      successfully with double frozen-embryo transfer.

PMID- 18083173
TI  - A modified Mainz II pouch technique for management of refractory vesicovaginal
      fistulas: patient focused outcomes.
AB  - OBJECTIVE: To follow-up the quality of life outcomes in 2 women who underwent a
      modified Mainz II pouch procedure for refractory vesicovaginal fistulas. METHOD:
      Two Nigerian patients were located after undergoing a modified Mainz II pouch
      procedure. They were interviewed 1-2 years postprocedure regarding subsequent
      sexual function, pregnancy outcomes, and daily life. RESULT: After undergoing the
      procedure the patients had resumed sexual function, had become pregnant, and had
      delivered viable neonates. They were also able to provide for their families.
      CONCLUSION: A urinary diversion procedure for management of refractory
      vesicovaginal fistula can restore quality of life.

PMID- 18083174
TI  - Greater adverse effects of cholesterol and diabetes on carotid intima-media
      thickness in South Asian Indians: comparison of risk factor-IMT associations in
      two population-based surveys.
AB  - Asian Indians appear particularly susceptible to coronary heart disease compared
      with other ethnic groups. We compared the effects of vascular risk factors on
      carotid intima-media thickness (IMT) in a population of South Asians from Andhra
      Pradesh, India with a population of Caucasians from Perth, Australia.
      Cardiovascular risk factors and ultrasound-assessed carotid IMT were measured in
      randomly selected adults from two villages in rural India (n=303) and compared to
      those for randomly sampled adults from Australia (n=1111). Regression models with
      interaction terms were used to compare the strengths of associations between risk
      factors and carotid IMT, in these two populations. There were stronger
      associations of cholesterol (p for interaction=0.009) and diabetes (p=0.04) with
      carotid IMT in the Indian compared to the Australian population. Also, while
      increasing HDL-cholesterol was associated with decreasing carotid IMT in the
      Australian population the reverse was true for the Indian population (p<0.001).
      The associations with IMT of blood pressure, triglycerides, age, HDL to total
      cholesterol ratio, glucose, BMI, waist, waist to hip ratio and smoking were not
      different between the populations. Greater adverse effects of total cholesterol
      and diabetes on atherosclerosis and no protective effect of HDL-cholesterol
      amongst Asian Indians provide a novel possible explanation for observed excess
      rates of cardiovascular disease amongst these populations.

PMID- 18083175
TI  - Structural analysis of platycosides in Platycodi Radix by liquid
      chromatography/electrospray ionization-tandem mass spectrometry.
AB  - Platycosides extracted from Platycodi Radix were analyzed by HPLC coupled with
      electrospray ionization multistage tandem mass spectrometry (HPLC/ESI-MS(n)).
      Predominant [M+Na](+) ions in positive mode and [M-H](-) ions in negative mode in
      the direct ESI-MS spectra of extract provided information on molecular weights,
      but minor components and isomers could not be discriminated. However, combining
      HPLC and ESI-MS(n), allowed eleven platycosides, including four acetylated
      platycodin isomers and two prosapogenines to be analyzed. During MS(2) analysis
      conducted to elucidate the structures of platycosides, fragment ions provided
      information on sugar moieties attached at C-28 of triterpene structure of the
      platycosides. Glycosidic bond cleavages at C-3 were revealed by fragment ions in
      MS(3) spectra. Some characteristic fragment ions not related to sugar bond
      cleavage revealed that an esterified triterpene is linked to sugars at C-28. The
      only sugar ring-cross cleavage corresponding to 90 Da in the negative MS(2)
      spectrum took place at an arabinosyl sugar moiety. By using HPLC/ESI-MS(n), three
      acetylated platycosides in Platycodi Radix extract were newly identified.

PMID- 18083176
TI  - Editorial on "Gas chromatographic high-throughput screening techniques in
      catalysis" by O. Trapp.

PMID- 18083177
TI  - Effect of Na4O7P2 on Cu powder preparation from Cu2O-water slurry system.
AB  - A unique approach is presented for preparing highly dispersed ultrafine copper
      particles from cuprous oxide slurry using a wet chemical reaction with hydrazine
      (N2H4) as a reductant along with an appropriate addition of sodium pyrophosphate
      (Na4O7P2) as a surfactant. It was found that very thin oxidized surfaces on the
      copper particles are formed during the reaction in the solution and subsequently
      sodium pyrophosphate plays an important role in the zeta potential of the
      particles, affecting their dispersion and growth significantly. The copper
      particles at low zeta potential easily aggregate and grow to bigger ones, whereas
      they at high zeta potential keep away each other and grew individually to
      ultrafine size. Additionally, a model for the copper particles growth in
      accordance with dispersion is proposed.

PMID- 18083178
TI  - Equilibrium partition of polycyclic aromatic hydrocarbons in cloud point
      extraction with a silicone surfactant.
AB  - In the cloud point extraction (CPE) process with PEG/PPG-18/18 dimethicone, the
      flexible chain structure of the silicone surfactant efficiently decreased the
      water content remaining in the surfactant-rich phase, compared with conventional
      nonionic surfactants, represented by Triton X-114. Meanwhile, the phase volume
      ratio of surfactant-rich phase to aqueous phase obtained in the silicone
      surfactant CPE system was found to be maintained at a low value with increasing
      surfactant concentration; whereas a rapid increase tendency was commonly observed
      in that of other nonionic surfactants. Based on these advantages, the equilibrium
      partition of three polycyclic aromatic hydrocarbons (PAHs), anthracene,
      phenanthrene and pyrene, was studied in the CPE process with PEG/PPG-18/18
      dimethicone. Equilibrium parameters, including preconcentration factor,
      distribution coefficient and recovery, were determined, and the performance was
      compared with that of another related CPE research, where Tergitol 15-S-7 was
      used. Due to the low surfactant-rich phase volume, higher concentrations of the
      three PAHs in the surfactant-rich phase, and the resulting higher
      preconcentration factors and distribution coefficients were able to be achieved
      at the same time. Moreover, the great performance was able to be maintained even
      at a high surfactant concentration or PAHs initial concentration.

PMID- 18083179
TI  - Diffusion of ions in unsaturated porous materials.
AB  - In a salinity gradient, the diffusion of ions through the connected porosity of a
      porous and charged material is influenced by the charged nature of the interface
      between the pore water and the solid. This influence is exerted through the
      generation of a macroscopic electrical field termed the diffusion or membrane
      potential. This electrical field depends on the excess of counterions located in
      the pore space counterbalancing the charge density of the surface of the solid.
      In unsaturated porous materials, we have to consider (1) the effect of the
      charged nature of the air/water interface, (2) the increase of the counterion
      density as the counterions are packed in a smaller volume when the saturation of
      the nonwetting phase (air) increases, and (3) the influence of the water
      saturation upon the tortuosity of the water phase. The volume average of the
      Nernst-Planck equation is used to determine the constitutive equations for the
      coupled diffusion flux and current density of a multicomponent electrolyte in
      unsaturated conditions. We assume that water is the wetting phase for the solid
      phase. We neglect the electro-osmotic flow in the coupled constitutive equations
      and the deformation of the medium (the medium is assumed to be both isotropic and
      rigid). This model explains well the observed tendency of strong decreases of the
      apparent diffusion coefficient of ions with the decrease of the saturation of the
      water phase under steady-state conditions. This decrease is mainly due to the
      influence of the saturation upon the tortuosity of the water phase.

PMID- 18083180
TI  - Time resolved alteration process of oxide glasses.
AB  - Dissolution of oxide glasses by water has been studied by small angles X-ray
      scattering. It is shown that the altered residual surface layer due to
      dissolution and recondensation of Si atoms is a porous material with nanometer
      size pores. Based on five elements oxide glass (18NaO2-17B2O3-4CaO-yZrO2-(61
      y)SiO2 with y=0, 1, 2, 4 and 8) the experiment highlights a strong influence of
      insoluble element on both the kinetic of alteration and the structure of the
      altered layer. It is shown that above 2% Zr content, the fraction of porous
      volume and the surface of exchange in the altered layer pass through a maximum
      value in the first hours of alteration corresponding to an overshoot of Si
      lixiviation without recondensation as the saturation limit is not reached. When
      the saturation limit is reached the porous volume fraction is just below the
      fraction of volume occupied primarily by the sodium and the boron.

PMID- 18083181
TI  - The strength of liquid bridges in random granular materials.
AB  - The strength of capillary bridges in randomly packed granular media was analyzed
      by means of computer simulations. A novel simulation method, based on the
      tracking of moving interfaces, has been implemented and used for determining the
      equilibrium shape of capillary bridges in a granular medium under a range of
      liquid saturations and solid-phase geometry. The net force acting on each grain
      due to the capillary bridges was evaluated, as well as the aggregate force acting
      between two wet granular media during their separation in the normal directions.
      The simulation results are consistent with previous experimental observations and
      reveal interesting phenomena such as the existence of a maximum in the tensile
      strength of a wet granular medium as function of liquid saturation.

PMID- 18083182
TI  - Viscous coalescence of expanding low-viscosity drops; the dueling drops
      experiment.
AB  - A new experimental device was designed and developed for the systematic study of
      the interaction of two, very small low viscosity expanding drops that were pushed
      out of the ends of two aligned opposing capillaries into a polymeric liquid. The
      idea of this experiment is to mimic the interactions of two expanding bubbles
      during the formation of polymeric foams; for convenience, we call this device the
      dueling drops experiment. In the current setup, we are able to grow drops (50-200
      microm maximum diameter) at a controlled flow rate (down to 0.1 microl/day).
      Optical observation of the pair of growing drops was achieved by the use of an
      optical zoom lens system for a side view, and a "long-range" microscope for a top
      view, thus ensuring complete alignment of the capillaries and partial observation
      of the thin-film. Measurements are reported for the drainage time between the
      apparent initial contact of the drops and film rupture. A simple scaling theory
      was developed based on the drainage of two approaching flat disk-like interfaces,
      the radius of which expands throughout the interaction as the volume of the drop
      increases.

PMID- 18083183
TI  - Effects of calcination temperature on the pore size and wall crystalline
      structure of mesoporous alumina.
AB  - In this paper, mesoporous alumina with different pore sizes and wall crystalline
      structures was synthesized at calcination temperatures over 550 degrees C. The
      characterization of the samples calcined at 550, 800, 1100, and 1300 degrees C,
      respectively, was performed using TEM, XRD, FTIR, TG/DTA, and N2
      adsorption/desorption techniques. The correlation between pore size and wall
      crystalline structure on calcination temperature was systematically investigated.

PMID- 18083184
TI  - Synthesis of nanocrystalline calcium phosphate in microemulsion--effect of nature
      of surfactants.
AB  - Nanosized calcium phosphate (CP) powders have been synthesized by an inverse
      microemulsion system using kerosene as the oil phase, a cationic surfactant
      Aliquat 336, a non-ionic surfactant Tween 20 and their mixture and aqueous
      solutions of calcium nitrate tetrahydrate and biammonium hydrogen phosphate as
      the water phase. It has been found that the nature of surfactants played an
      important role to regulate the size and morphologies of the calcium phosphate
      nanoparticles. The cationic surfactant Aliquat 336 has been found to regulate the
      nucleation and crystal growth. The synthesized powders have been comprehensively
      characterized using transmission electron microscopy (TEM), scanning electron
      microscopy (SEM), powder X-ray diffraction (XRD) and Fourier transform infrared
      spectroscopy (FTIR). Our results show that the brushite (DCPD) is the major phase
      comprising the calcium phosphate nanoparticles. In mixed surfactants mediated
      system a morphological controlled highly crystalline particles have been
      synthesized. Further, the role of Aliquat 336 has been established and a
      plausible synthetic mechanism has been proposed.

PMID- 18083185
TI  - Bone marrow pathology in dogs and cats with non-regenerative immune-mediated
      haemolytic anaemia and pure red cell aplasia.
AB  - Many dogs and cats with immune-mediated haemolytic anaemia (IMHA) lack a bone
      marrow erythroid regenerative response. To better understand the failure of the
      bone marrow to respond to the anaemia, bone marrow pathology associated with non
      regenerative IMHA and pure red cell aplasia (PRCA) was reviewed. Eighty-two
      affected dogs and 57 affected cats were identified from a population presenting
      to a referral hospital over a 10-year period. Fifty-five dogs had non
      regenerative IMHA (38 had bone marrow erythroid hyperplasia and 17 had erythroid
      maturation arrest) and 27 had pure red cell aplasia (PRCA). Twenty-eight cats had
      non-regenerative IMHA (24 had erythroid hyperplasia and 4 had erythroid
      maturation arrest) and 29 had PRCA. A variety of pathological changes were
      observed in bone marrow aspirates and core biopsy specimens taken from these
      animals. These changes included dysmyelopoiesis, myelonecrosis, myelofibrosis,
      interstitial oedema, haemorrhage, acute inflammation, haemophagocytic syndrome,
      lymphocyte aggregation, and lymphocyte or plasma cell hyperplasia. In both dogs
      and cats, dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema,
      haemorrhage, acute inflammation and haemophagocytic syndrome were primarily noted
      in bone marrow specimens where there was evidence of erythroid hyperplasia. These
      animals were also more often neutropenic and thrombocytopenic, and had decreased
      60 day survival when compared with dogs or cats with non-regenerative anaemia
      associated with erythroid maturation arrest or PRCA. Therefore, the pathogenesis
      of the non-regenerative anaemia in non-regenerative IMHA may involve both
      antibody-mediated destruction of bone marrow precursor cells and pathological
      events within the bone marrow that result in ineffective erythropoiesis.

PMID- 18083186
TI  - Application of nine-color flow cytometry for detailed studies of the phenotypic
      complexity and functional heterogeneity of human lymphocyte subsets.
AB  - Innate and adaptive cellular immunity is initiated, directed and regulated by a
      vast array of cell surface receptors. Attempts to harness the cellular immune
      system in translational settings such as immunotherapy and vaccine development
      require tools to accurately describe and isolate lymphocytes with specific
      characteristics. One such tool, flow cytometry, is undergoing a revolution in
      instrumentation and reagents, providing opportunities for high resolution
      phenotypic and functional analysis of lymphocytes. Here, we demonstrate how nine
      color flow cytometry can be adapted, optimized and applied to investigate the
      phenotypic complexity and functional heterogeneity of human lymphocyte subsets.
      We provide examples of studies of adaptive T cell responses against viruses, as
      well as the assessment of CD1d-restricted NKT cells and NK cells. We discuss the
      importance of this technology for detailed investigations of lymphocyte subsets
      in studies of infectious diseases and cancer.

PMID- 18083187
TI  - Ability of male Queensland fruit flies to inhibit receptivity in multiple mates,
      and the associated recovery of accessory glands.
AB  - Mating success of male insects is commonly determined by their ability to find
      and copulate with multiple females, but is also determined by their ability to
      transfer an effective ejaculate. In order to succeed in these tasks, males must
      first succeed in replenishing the necessary reproductive reserves between mating
      opportunities. We here investigate the ability of male Queensland fruit flies ('Q
      fly') to recover from their first matings in time to both mate again the
      following day and to induce sexual inhibition in successive mates. We have
      previously found that accessory gland fluids (AGFs) transferred in the ejaculate
      of male Q-flies are directly responsible for induction of sexual inhibition in
      their mates. We here investigate changes in male accessory gland, testis and
      ejaculatory apodeme dimensions that are likely to reflect depletion and recovery
      of contents. We found no differences between virgin and previously mated males in
      their ability to obtain matings or to induce sexual inhibition in their mates,
      indicating a full recovery of the necessary reproductive reserves between mating
      opportunities. Whereas no changes were detected in testis or ejaculatory apodeme
      size following mating, the recovery of male ability to inhibit female remating
      was closely reflected in the mesodermal accessory gland dimensions; these
      accessory glands greatly diminished in size (length and area) immediately after
      mating, with recovery commencing between 5.5 and 11 h after mating. The accessory
      glands then expanded to reach their original size in time to mate the following
      day and induce sexual inhibition in the next mate.

PMID- 18083188
TI  - Gadolinium limits myocardial infarction in the rat: dose-response, temporal
      relations and mechanisms.
AB  - The lanthanide cation, gadolinium (Gd) attenuates post-ischemic myocardial
      stunning. This study tests the hypothesis that Gd also preconditions the
      myocardium against infarction following ischemia-reperfusion (IR) and explores
      potential mechanisms underlying Gd-induced cardioprotection. Regional myocardial
      infarction was induced in rats by occluding the left anterior descending artery
      for 30 min and reperfusing for 120 min. Rats (n=6/group) were administered
      intravenous Gd (1 to 100 micromol/kg) 15 min prior to ischemia. Hearts were
      excised after reperfusion to determine infarct size (IS) and area at risk (AAR).
      The ratio IS/AAR (%) was reduced by Gd in a "U"-shaped, dose-dependent manner.
      The minimum dose that reduced IS/AAR was 5 micromol/kg (52+/-5% vs. 64+/-4%),
      while the dose that reduced IS/AAR maximally was 20 micromol/kg (44+/-4%). Gd
      also reduced IS/AAR when given 1 min before reperfusion (47+/-3%) but not when
      given 10 s after reperfusion (60+/-3%). Cardioprotection was maintained if IR was
      delayed 24-72 h after Gd administration. Cardioprotection by Gd was abolished by
      inhibition of JAK-2 with AG-490, of p42/44 MAPK with PD98059 or of K(ATP)
      channels with glibenclamide. None of these agents given alone altered IS/AAR
      compared with controls. Inhibition of JAK-2 also blocked Gd-induced delayed
      cardioprotection. Gd may have broad potential roles in IR, as it conferred
      immediate cardioprotection when given prior to ischemia or prior to reperfusion
      and delayed cardioprotection for up to 72 h after administration. The mechanism
      underlying Gd-induced preconditioning appears to be multi-factorial, involving
      JAK-2, STAT-3 and p44 MAPK pathways, as well as K(ATP) channels.

PMID- 18083190
TI  - Refolding SDS-denatured proteins by the addition of amphipathic cosolvents.
AB  - Sodium dodecyl sulfate (SDS) is a highly effective and widely used protein
      denaturant. We show that certain amphipathic cosolvents such as 2-methyl-2,4
      pentanediol (MPD) can protect proteins from SDS denaturation, and in several
      cases can refold proteins from the SDS-denatured state. This cosolvent effect is
      observed with integral membrane proteins and soluble proteins from either the
      alpha-helical or the beta-sheet structural classes. The SDS/MPD system can be
      used to study processes involving native protein states, and we demonstrate the
      reversible thermal denaturation of the outer membrane protein PagP in an SDS/MPD
      buffer. MPD and related cosolvents can modulate the denaturing properties of SDS,
      and we describe a simple and effective method to recover refolded, active protein
      from the SDS-denatured state.

PMID- 18083191
TI  - Conformation of pseudoazurin in the 152 kDa electron transfer complex with
      nitrite reductase determined by paramagnetic NMR.
AB  - Copper-containing nitrite reductase is able to catalyze the reduction of nitrite
      with a turnover rate of several hundreds per second. Electrons for the reaction
      are donated by the electron transfer protein pseudoazurin. The process of protein
      complex formation, electron transfer and dissociation must occur on the
      millisecond timescale to enable the fast turnover of the enzyme. The structure of
      this transient protein complex has been studied using paramagnetic NMR
      spectroscopy. Gadolinium complexes were attached specifically through two
      engineered Cys residues on three sites on the surface of nitrite reductase,
      causing strong distance-dependent relaxation effects on the residues of
      pseudoazurin. Docking of the two proteins based on these NMR-derived distance
      restraints and the chemical shift perturbation data shows convergence to a
      cluster of structures with an average root-mean-square deviation of 1.5 A. The
      binding interface consists of polar and non-polar residues surrounded by charges.
      The interprotein distance between the two type-1 copper sites is 15.5(+/-0.5) A,
      enabling fast interprotein electron transfer. The NMR-based lower limit estimate
      of 600 s(-1) for the dissociation rate constant and the fast electron transfer
      are consistent with the transient nature of the complex.

PMID- 18083189
TI  - Coarse-grained models for simulations of multiprotein complexes: application to
      ubiquitin binding.
AB  - We develop coarse-grained models and effective energy functions for simulating
      thermodynamic and structural properties of multiprotein complexes with relatively
      low binding affinity (K(d) >1 microM) and apply them to binding of Vps27 to
      membrane-tethered ubiquitin. Folded protein domains are represented as rigid
      bodies. The interactions between the domains are treated at the residue level
      with amino-acid-dependent pair potentials and Debye-Huckel-type electrostatic
      interactions. Flexible linker peptides connecting rigid protein domains are
      represented as amino acid beads on a polymer with appropriate stretching,
      bending, and torsion-angle potentials. In simulations of membrane-attached
      protein complexes, interactions between amino acids and the membrane are
      described by residue-dependent short-range potentials and long-range
      electrostatics. We parameterize the energy functions by fitting the osmotic
      second virial coefficient of lysozyme and the binding affinity of the ubiquitin
      CUE complex. For validation, extensive replica-exchange Monte Carlo simulations
      are performed of various protein complexes. Binding affinities for these
      complexes are in good agreement with the experimental data. The simulated
      structures are clustered on the basis of distance matrices between two proteins
      and ranked according to cluster population. In approximately 70% of the
      complexes, the distance root-mean-square is less than 5 A from the experimental
      structures. In approximately 90% of the complexes, the binding interfaces on both
      proteins are predicted correctly, and in all other cases at least one interface
      is correct. Transient and nonspecifically bound structures are also observed.
      With the validated model, we simulate the interaction between the Vps27
      multiprotein complex and a membrane-tethered ubiquitin. Ubiquitin is found to
      bind preferentially to the two UIM domains of Vps27, but transient interactions
      between ubiquitin and the VHS and FYVE domains are observed as well. These
      specific and nonspecific interactions are found to be positively cooperative,
      resulting in a substantial enhancement of the overall binding affinity beyond the
      approximately 300 microM of the specific domains. We also find that the
      interactions between ubiquitin and Vps27 are highly dynamic, with conformational
      rearrangements enabling binding of Vps27 to diverse targets as part of the
      multivesicular-body protein-sorting pathway.

PMID- 18083192
TI  - Examining the dynamic energy landscape of an antiporter upon inhibitor binding.
AB  - Previously, we applied single-molecule force spectroscopy to detect and locate
      interactions within the functional Na(+)/H(+) antiporter NhaA from Escherichia
      coli. It was observed that the binding of the inhibitor 2-aminoperimidine
      established interactions different from those introduced by the binding of the
      native ligand. To understand the inhibitory mechanism of the inhibitor, we
      applied single-molecule dynamic force spectroscopy to reconstruct the energy
      landscape of NhaA. Dynamic force spectroscopy revealed that the energy landscape
      of the antiporter remained mainly unchanged except for the energy barrier of the
      functionally important transmembrane alpha-helix IX. Inhibitor binding set this
      domain into a newly formed deep and narrow energy minimum that kinetically
      stabilized alpha-helix IX and reduced its conformational entropy. The entropy
      reduction of alpha-helix IX is thought to inhibit its functionally important
      structural flexibility, while the deeper energy barrier shifted the population of
      active antiporters towards inhibited antiporters.

PMID- 18083193
TI  - 3D reconstruction of mammalian septin filaments.
AB  - Mammalian septins are a family of guanosine triphosphate-binding proteins thought
      to play a role in a number of key cellular processes, such as cytokinesis,
      protein scaffolding and vesicle trafficking. Although their precise functions
      remain to be determined, electron microscopy has shown septin filament formation
      in vitro and a role as a cytoskeletal polymer has been proposed. Here, we present
      a 3D reconstruction of septin filaments determined using electron microscopy of
      negatively stained specimens and single-particle image processing. Septin was
      isolated from rat brain as an approximately 240-kDa complex, from which
      immunoblotting and N-terminal sequencing identified the major components as
      septins 3, 5 and 7. Electron microscopy and single-particle analysis indicated
      that the majority of the septin filaments were approximately 27 nm long. A
      comparison of 3D volumes obtained using two independent starting models (a row of
      spheres or a helix) and projection matching techniques revealed no major
      differences at the final resolution of 27 A, and this structure was highly
      reproducible when the entire procedure was repeated several times. The
      reconstruction revealed three apparent subunits, each separated by a cleft; these
      subunits were similar, but not identical, possibly indicating multiple isoforms
      within each filament. In some views a smaller cleft appeared to separate the
      subunits into two smaller regions, perhaps reflecting the presence of septin
      dimers. This is the first 3D reconstruction of the native septin assembly, and
      appears compatible with the hypothesis that the septin complex is a hexamer
      consisting of dimers or heterotrimers. Further investigations are necessary to
      confirm how the structure of the filaments determined in the present study
      correlates with the roles of septins in vivo.

PMID- 18083194
TI  - Erythrocyte lysis in isotonic solution of ammonium chloride: theoretical modeling
      and experimental verification.
AB  - A mathematical model of erythrocyte lysis in isotonic solution of ammonium
      chloride is presented in frames of a statistical approach. The model is used to
      evaluate several parameters of mature erythrocytes (volume, surface area,
      hemoglobin concentration, number of anionic exchangers on membrane, elasticity
      and critical tension of membrane) through their sphering and lysis measured by a
      scanning flow cytometer (SFC). SFC allows measuring the light-scattering pattern
      (indicatrix) of an individual cell over the angular range from 10 degrees to 60
      degrees . Comparison of the experimentally measured and theoretically calculated
      light scattering patterns allows discrimination of spherical from non-spherical
      erythrocytes and evaluation of volume and hemoglobin concentration for individual
      spherical cells. Three different processes were applied for erythrocytes
      sphering: (1) colloid osmotic lysis in isotonic solution of ammonium chloride,
      (2) isovolumetric sphering in the presence of sodium dodecyl sulphate and albumin
      in neutrally buffered isotonic saline, and (3) osmotic fragility test in
      hypotonic media. For the hemolysis in ammonium chloride, the evolution of
      distributions of sphered erythrocytes on volume and hemoglobin content was
      monitored in real-time experiments. The analysis of experimental data was
      performed in the context of a statistical approach, taking into account that
      parameters of erythrocytes vary from cell to cell.

PMID- 18083195
TI  - A viral load-based cellular automata approach to modeling HIV dynamics and drug
      treatment.
AB  - We formulated a novel cellular automata (CA) model for HIV dynamics and drug
      treatment. The model is built upon realistic biological processes, including the
      virus replication cycle and mechanisms of drug therapy. Viral load, its effect on
      infection rate, and the role of latently infected cells in sustaining HIV
      infection are among the aspects that are explored and incorporated in the model.
      We assume that the calculation of the number of cells in the neighborhood which
      influences the center cell's state is based on the viral load. This variable-cell
      neighborhood enables the simulation of an infection rate that is correlated to
      the viral load. This approach leads to a new and flexible way of modeling HIV
      dynamics and allows for the simulation of different antiretroviral drug
      treatments based on their individual and combined effects. The results of the
      simulation show the three phases of HIV dynamics (acute, chronic, and AIDS) and
      the additional drug response phase when drug treatment is added. The dynamics
      from the model qualitatively match clinical data. Drug treatment combinations
      with reverse transcriptase inhibitors and protease inhibitors are simulated using
      various drug efficacies. The results indicate that the model can be very useful
      in evaluating different drug therapy regimens.

PMID- 18083196
TI  - Consequences of the fractal architecture of trees on their structural measures.
AB  - While the mechanics of trees are well known, a systematic and comprehensive study
      of the mechanical consequences of a tree's fractal structure has been lacking.
      Here, we analyze the structure of botanical trees using computer modeling and
      show that many relevant measures of support throughout all the branches of a tree
      follow specific patterns which can be described by characteristic probability
      distributions and well-defined spatial relationships. Most notably, moments,
      forces, and axial and shear stresses throughout the different branches all
      exhibit power-law distributions. These results suggest a new approach to the
      study of the mechanics of trees, one accounting for the implications of the above
      results.

PMID- 18083197
TI  - Why the wrinkling transition in partially polymerized membranes is not universal?
      Fractal-multifractal hierarchy.
AB  - When partially polymerized membranes wrinkle they exhibit a passage from a
      conventional buckling (due to an instability caused by chiral symmetry breaking)
      at low polymerization to a local roughening (due to a frustration in the local
      packing of the chiral molecules composing the membrane) as a function of the
      polymerization of the lipids aliphatic tails. This transition was found to be non
      universal and here we used neutron scattering to elucidate that this behavior is
      due to the onset of stretching in the membrane accompanied by a bilayer thickness
      variation. Close to the percolation limit this deformation is plastic similar to
      mutated lysozymes. We draw an analogy between this transition and echinocytes in
      red blood cells.

PMID- 18083198
TI  - Microcolony and biofilm formation as a survival strategy for bacteria.
AB  - Bacterial communities such as biofilms are widely recognized as being important
      for survival and persistence of bacteria in harsh environments. Mechanistic
      models of biofilm growth indicate that the way in which the surface is seeded can
      effect the morphology of simulated biofilms. Experimental studies indicate that
      genes which are important for chemotaxis also influence biofilm formation,
      perhaps by influencing aggregation on a surface. Understanding aggregation and
      microcolony formation could therefore help clarify factors influencing biofilm
      formation and illuminate how groups influence the fitness of bacteria. In this
      paper I develop an individual based model to examine how different behaviors
      involved in microcolony formation on a surface determine patterns of group sizes
      and link patterns to bacterial fitness.

PMID- 18083200
TI  - cDNA microarray analysis of the differentially expressed genes involved in murine
      pre-osteoclast RAW264.7 cells proliferation stimulated by dexamethasone.
AB  - Glucocorticoids (GCs) are hormones with anti-inflammatory and immuno-suppressive
      effects. The use of hormonal medicine like GCs may cause systemic adverse
      effects. In the present study, the cellular response of murine pre-osteoclast
      cell line RAW264.7 to dexamethasone (DEX) was investigated and the result
      demonstrated that DEX may stimulate RAW264.7 cells proliferation. Changes in gene
      expression involved in RAW264.7 cells proliferation stimulated by dexamethasone
      were investigated using cDNA microarrays containing 1000 cDNAs. It was found that
      67 genes were regulated by DEX and could be grouped into 8 functional categories,
      including cell cycle regulation, cell survival, metabolism, pro-inflammatory
      effect, cytoskeleton, proteasome, signaling transduction and transcription
      factors. Moreover, some signaling pathways that involve in modulation of DEX on
      RAW264.7 cells functions were identified, including p53, 14-3-3 gamma, MAPK, Elk
      1, I kappa B and Ifn related pathways.

PMID- 18083201
TI  - Natural and anthropogenic nitrogen uptake by bloom-forming macroalgae.
AB  - The frequency and duration of macroalgal blooms have increased in many coastal
      waters over the past several decades. We used field surveys and laboratory
      culturing experiments to examine the nitrogen content and delta(15)N values of
      Ulva and Gracilaria, two bloom-forming algal genera in Narragansett Bay, RI
      (USA). The northern end of this bay is densely populated with large sewage
      treatment plant nitrogen inputs; the southern end is more lightly populated and
      opens to the Atlantic Ocean. Field-collected Ulva varied in delta(15)N among
      sites, but with two exceptions had delta(15)N above 10 per thousand, reflecting a
      significant component of heavy anthropogenic N. This variation was not correlated
      with a north-south gradient. Both Ulva and Gracilaria cultured in water from
      across Narragansett Bay also had high signals (delta(15)N= approximately 14-17
      per thousand and 8-12 per thousand, respectively). These results indicate that
      inputs of anthropogenic N can have far-reaching impacts throughout estuaries.

PMID- 18083202
TI  - Dissociable top-down anticipatory neural states for different linguistic
      dimensions.
AB  - When preparing to perform a task, the brain settles into task-set states which
      are relevant for the selection of the appropriate task-rules and stimulus
      response mappings. The way this selection takes place within the Language domain
      is not well understood. We used high-density electrophysiological recordings
      while participants were engaged in a task in which cues directed their attention
      to the orthography, phonology or semantics of upcoming target words (or to the
      shape of novel symbols). To study the specificity of the brain preparatory states
      to different goals within the language domain, we contrasted the topographical
      maps associated with the cues for these different tasks, and explored whether the
      need of task-set reconfiguration modulated this preparatory activity. As a
      complement to the topographical analyses, we compared the amplitude of the cue
      locked ERPs across task conditions. The topographical maps differed only at the
      end of the epoch. During this time window, each task-cue generated distinct
      topographical activity, which was also different depending on whether it involved
      a switch in task-set or not. These results suggest that, when the time of target
      onset approaches, the generators of anticipatory-biasing brain states for
      different language tasks vary depending on the nature of the task.

PMID- 18083203
TI  - Prism adaptation aftereffects in stroke patients with spatial neglect:
      pathological effects on subjective straight ahead but not visual open-loop
      pointing.
AB  - Prism adaptation to rightward optical shifts during visually guided pointing is
      considered a promising intervention in right-hemisphere stroke patients with left
      spatial neglect. Conventionally, prism adaptation is assessed via aftereffects,
      on subjective straight ahead (SSA) pointing with eyes closed; or by visual open
      loop pointing (VOL), i.e. pointing to a visual target without seeing the hand.
      Previous data suggest indirectly that prism aftereffects in neglect patients may
      be larger (pathologically so) when assessed by SSA than by VOL. But these
      measures have never been directly compared within the same patients after
      identical prism exposure. Accordingly we implemented both measures here within
      the same group of 13 neglect patients and 13 controls. Prism aftereffects were
      much larger for SSA than VOL in neglect patients, falling outside the normative
      range only for SSA. This may arise because the SSA task can itself involve
      aspects of neglect that may be ameliorated by the prism intervention, hence
      showing abnormal changes after prisms. The extent of SSA change after prisms
      varied between patients, and correlated with improvements on a standard
      cancellation measure for neglect. The lesions of patients who did versus did not
      show neglect improvement immediately after prisms provide an initial indication
      that lack of improvement may potentially relate to cortical damage in right
      intraparietal sulcus and white matter damage in inferior parietal lobe and middle
      frontal gyrus. Future studies of possible rehabilitative impact from prisms upon
      neglect may need to consider carefully how to measure prism adaptation per se,
      separately from any impact of such adaptation upon manifestations of neglect.

PMID- 18083204
TI  - Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific
      adverse effects in aggregating brain cell cultures.
AB  - Despite the widespread use of Cannabis as recreational drug or as medicine,
      little is known about its toxicity. The accumulation, metabolism and toxicity of
      THC were analyzed 10 days after a single treatment, and after repeated exposures
      during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were
      used as in vitro model, as well as aggregates enriched either in neurons or in
      glial cells. It was found that THC accumulated preferentially in neurons, and
      that glia-neuron interactions decreased THC accumulation. The quantification of
      11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC
      metabolism. No cell-type difference was found for the metabolite 11-OH-THC,
      whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was
      found at THC concentrations of 2 microM in single treatment and of 1 microM and 2
      microM in repeated treatments. Neurons, and particularly GABAergic neurons, were
      most sensitive to THC. Only the GABAergic marker was affected after the single
      treatment, whereas the GABAergic, cholinergic and astrocytic markers were
      decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed
      effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The
      expression of the cytokine IL-6 was upregulated 48 h after the single treatment
      with 5 microM of THC or JWH 015, whereas the expression of TNF-alpha remained
      unchanged. These results suggest that the adverse effects of THC were related
      either to THC accumulation or to cannabinoid receptor activation and associated
      with IL-6 upregulation.

PMID- 18083205
TI  - Heterodimeric neurotoxic phospholipases A2--the first proteins from venom of
      recently established species Vipera nikolskii: implication of venom composition
      in viper systematics.
AB  - For the first time the venom of recently established viper species Vipera
      nikolskii was fractionated and two heterodimeric phospholipases A(2) (HDP-1 and
      HDP-2) were isolated. Isolation of HDP-1 and HDP-2 is the first indication of the
      presence of two heterodimeric phospholipases A(2) in the venom of one viper
      species. When tested on the frog neuromuscular junction, isolated proteins
      affected neuromuscular transmission acting presynaptically. Using RP-HPLC, each
      heterodimer was separated into two monomeric subunits: basic phospholipase A(2)
      (HDP-1P and HDP-2P) and acidic component without enzymatic activity (HDP-In). The
      complete primary structures of subunits were deduced from corresponding sequences
      of cDNAs. The determined amino acid sequences were homologous to those of vipoxin
      from Vipera ammodytes and vaspin from Vipera aspis. Similar proteins were not
      found earlier in the well-studied venom of Vipera berus, the species from which
      V. nikolskii was recently separated. Our finding supports at the biochemical
      level the correctness of the establishment of V. nikolskii as an independent
      species. The finding of similar proteins (HDPs and vipoxin) in geographically
      remote species (V. nikolskii and V. ammodytes) corroborates the hypothesis about
      the pre-existence of genes encoding these proteins in all true viper species and
      their expression under certain conditions.

PMID- 18083206
TI  - Interactions of LSECtin and DC-SIGN/DC-SIGNR with viral ligands: Differential pH
      dependence, internalization and virion binding.
AB  - The calcium-dependent lectins DC-SIGN and DC-SIGNR (collectively termed DC
      SIGN/R) bind to high-mannose carbohydrates on a variety of viruses. In contrast,
      the related lectin LSECtin does not recognize mannose-rich glycans and interacts
      with a more restricted spectrum of viruses. Here, we analyzed whether these
      lectins differ in their mode of ligand engagement. LSECtin and DC-SIGNR, which we
      found to be co-expressed by liver, lymph node and bone marrow sinusoidal
      endothelial cells, bound to soluble Ebola virus glycoprotein (EBOV-GP) with
      comparable affinities. Similarly, LSECtin, DC-SIGN and the Langerhans cell
      specific lectin Langerin readily bound to soluble human immunodeficiency virus
      type-1 (HIV-1) GP. However, only DC-SIGN captured HIV-1 particles, indicating
      that binding to soluble GP is not necessarily predictive of binding to virion
      associated GP. Capture of EBOV-GP by LSECtin triggered ligand internalization,
      suggesting that LSECtin like DC-SIGN might function as an antigen uptake
      receptor. However, the intracellular fate of lectin-ligand complexes might
      differ. Thus, exposure to low-pH medium, which mimics the acidic luminal
      environment in endosomes/lysosomes, released ligand bound to DC-SIGN/R but had no
      effect on LSECtin interactions with ligand. Our results reveal important
      differences between pathogen capture by DC-SIGN/R and LSECtin and hint towards
      different biological functions of these lectins.

PMID- 18083207
TI  - Biostability and disinfectant by-product formation in drinking water blended with
      UF-treated filter backwash water.
AB  - The overall objective of this study was to investigate the impact of blending
      membrane-treated water treatment plant (WTP) residuals with plant-filtered water
      on finished water quality in terms of biostability and disinfectant by-product
      (DBP) formation. Filter backwash water (FBWW) was treated with a pilot-scale
      ultrafiltration (UF) membrane to produce permeate that was blended with plant
      finished water. The batch studies involved storing samples for a specified time
      with a disinfectant residual to simulate residence time in the distribution
      system. Both chlorinated and non-chlorinated FBWW streams were evaluated, and the
      experimental design incorporated free chlorine, monochloramine, and chlorine
      dioxide in parallel to a model system that did not receive a disinfectant dose.
      The results of the study found that blending 10% UF-treated FBWW with plant
      filtered water did not have an impact on water biostability as monitored with
      heterotrophic plate counts (HPCs) or DBP concentrations as monitored by TTHM and
      HAA5 concentrations. However, the presence of preformed THM and HAA species found
      in chlorinated FBWW streams may result in higher levels of initial DBP
      concentrations in blended water matrices, and could have a significant impact on
      finished water quality in terms of meeting specific DBP guidelines or
      regulations.

PMID- 18083208
TI  - Concentrations and mobility of human pharmaceuticals in the world's largest
      wastewater irrigation system, Mexico City-Mezquital Valley.
AB  - Concentrations and retention of pharmaceutically active substances are crucial
      for assessing the environmental risk of medication of humans. We hypothesize that
      environmental introduction concentrations (EICs) of drugs in the Mexico City
      Mezquital Valley wastewater irrigation system can be estimated using information
      on water consumption, sales data, and excretion rates. EICs of six acidic and
      five basic drugs were calculated and compared with concentrations measured in
      wastewater, irrigation water, soil drainage, and springs by liquid chromatography
      electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). EICs of
      trimethoprim, erythromycin, naproxen, ibuprofen, and diclofenac in sewage equaled
      or exceeded the US FDA action limit of 1mug/L for detailed environmental risk
      assessment (ERA). Concentrations of clarithromycin, clindamycin, metoprolol,
      sulfasalazine, bezafibrate, and gemfibrozil were smaller. Calculated EICs of all
      compounds except metoprolol and clarithromycin were comparable to measured
      concentrations if excretion rates were considered. Whereas concentrations of
      basic compounds with positive or neutral charges were effectively reduced during
      reservoir storage and soil passage, acidic, anionic compounds were hardly
      retained. Though realistic EICs can be predicted for most substances, large
      deviations between EICs and measured concentrations in the case of metoprolol
      illustrate that estimated concentrations cannot substitute for monitoring
      programs.

PMID- 18083209
TI  - Leaching characteristics of stabilized/solidified fly ash generated from ash
      melting plant.
AB  - This study was designed to elucidate the leaching characteristics of
      stabilized/solidified (S/S) fly ash generated by ash-melting. For this study, pH
      dependent leaching tests, sequential extraction procedures, and column leaching
      tests were carried out. The pH-dependent leaching test results for Pb, Cu, and Zn
      showed that the heavy metal concentrations in the high-pH range were lower than
      the predicted values for hydroxide and carbonate. During sequential extraction,
      Cu and Pb were principally distributed in the S/S ashes' organic matter fraction
      in the chelating agent, suggesting that metals bind to the chelating agent. The
      percentage of the water-soluble fraction for Pb and Cu was low (<0.2 %). The fly
      ashes treated with a chelating agent and cement had low leachability potential
      for metals in the high-pH range. Column tests for S/S fly ashes showed that two
      leaching stages were distinguishable: one for short time, corresponding to faster
      metal leaching, and another for the leaching rate. Kinetic speciation was then
      applied to data obtained from column leaching tests. The first-order
      reaction/diffusion model showed a better fit for Ca, Pb, and Cu, suggesting that
      the initial dissolution of soluble compounds, such as metal chloride, was
      controlled by the first-order reaction (surface wash off). Subsequently,
      insoluble compounds such as hydroxide or carbonate might penetrate into the
      porous matrix by diffusion.

PMID- 18083210
TI  - Microbial degradation of chlorinated dioxins.
AB  - Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF)
      were introduced into the biosphere on a large scale as by-products from the
      manufacture of chlorinated phenols and the incineration of wastes. Due to their
      high toxicity they have been the subject of great public and scientific scrutiny.
      The evidence in the literature suggests that PCDD/F compounds are subject to
      biodegradation in the environment as part of the natural chlorine cycle. Lower
      chlorinated dioxins can be degraded by aerobic bacteria from the genera of
      Sphingomonas, Pseudomonas and Burkholderia. Most studies have evaluated the
      cometabolism of monochlorinated dioxins with unsubstituted dioxin as the primary
      substrate. The degradation is usually initiated by unique angular dioxygenases
      that attack the ring adjacent to the ether oxygen. Chlorinated dioxins can also
      be attacked cometabolically under aerobic conditions by white-rot fungi that
      utilize extracellular lignin degrading peroxidases. Recently, bacteria that can
      grow on monochlorinated dibenzo-p-dioxins as a sole source of carbon and energy
      have also been characterized (Pseudomonas veronii). Higher chlorinated dioxins
      are known to be reductively dechlorinated in anaerobic sediments. Similar to PCB
      and chlorinated benzenes, halorespiring bacteria from the genus Dehalococcoides
      are implicated in the dechlorination reactions. Anaerobic sediments have been
      shown to convert tetrachloro- to octachlorodibenzo-p-dioxins to lower chlorinated
      dioxins including monochlorinated congeners. Taken as a whole, these findings
      indicate that biodegradation is likely to contribute to the natural attenuation
      processes affecting PCDD/F compounds.

PMID- 18083211
TI  - Evaluation of the Spanish hot dip galvanising sector as a source of
      polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans.
AB  - A survey to estimate the polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs) emissions of Spanish hot dip galvanising
      sector was carried out during 2002. This investigation is the first presenting
      Spanish experimental data related to this industrial sector. Three different
      matrices: flue gas, ash and filter dust were tested to quantify the PCDD/Fs
      generated during the galvanising process. The organic source of PCDD/F formation
      could be from the insufficient degreasing o from inhibitors or additives used in
      the pickling steps such as quinoline, isoquinoline, 8-methylquinoline or
      polyether phosphoric acid. Low levels PCDD/Fs were achieved in air emissions when
      air control devices are used. On the contrary, filter dusts are highly
      contaminated; indicating that the absence of air control devices would increase
      the risk of fugitive emissions. Homologue profiles and Principal Component
      Analysis demonstrate there are differences in the formation mechanisms in the
      bath zone (ashes) compared to the stack location (filter dusts and air
      emissions), related to the de novo synthesis and reaction time. The annual PCDD/F
      emission to the atmosphere for this sector during 2002 has been estimated in
      0.023g I-TEQ. The emission factor of plants with air control devices has been
      calculated at 0.030microg I-TEQ/ton of galvanised steel.

PMID- 18083212
TI  - Sonophotocatalytic degradation of alazine and gesaprim commercial herbicides in
      TiO2 slurry.
AB  - The photocatalytic degradation of alazine and gesaprim commercial herbicides was
      carried out in aqueous TiO(2) suspensions under UV light (15W, 352 nm).
      Degradation of these herbicides was also observed by the combined effects of
      photocatalysis with sonolysis (sonophotocatalysis) using an ultrasound source of
      20kHz. Degradation profiles were recorded by measuring the concentration of the
      active compounds present in the alazine (alachlor and atrazine) and gesaprim
      (atrazine) by HPLC as a function of irradiation time (sound and/or light). Over
      90% of the active component in the gesaprim was abated and those in alazine were
      completely degraded. The content of total organic carbon and chemical oxygen
      demand was also monitored. Mineralization of the commercial herbicides was
      achieved. Over 80% of chemical oxygen demand abatement was attained for both
      herbicides with sonophotocatalysis at 150 min of irradiation time. The
      photocatalytic degradation of the herbicides followed a pseudo-first order
      kinetics and their rate constant was increased by the combined effects of
      sonolysis.

PMID- 18083213
TI  - Natural organic matter (NOM) in roof runoff and its impact on the Fe0 treatment
      system of dissolved metals.
AB  - The present work investigates the impacts and mechanisms associated with natural
      organic matter (NOM) in the Fe0 treatment system of Cu2+ and Zn2+ under roof
      runoff conditions. The NOM in runoff waters was characterized using XAD-4/8
      adsorption resins, copper complexation, acidic capacity and liquid chromatography
      with online carbon detection. Batch kinetic experiments and flow-through
      configurations were performed and the results of metal removal were elucidated
      taking into account the characteristics of NOM. Based on the findings, it is
      shown that NOM influences the removal of metals through several complex pathways.
      At an un-favored condition for adsorption of metals, i.e., on iron corrosion
      products, at pH<<pH(PZC), the previously adsorbed NOM noticeably enhances the
      overall removal of metals by forming of an oxide-NOM-metal ternary complex. In a
      more typical condition for roof runoff (i.e., pH-pHPZC), metal-ligand complexes
      in the bulk water as well as a competitive adsorption between them play important
      roles on the removal processes. A significant decrease in the treatment
      efficiency observed during flow-through configuration suggests a hinderance
      effect of NOM on corrosion of iron by surface coverage. The NOM fraction that
      mainly interacts with the removal of metals is a larger size hydrophobic fraction
      with high aromaticity. In the practical operation, continuous input of NOM will
      lessen the effectiveness of the treatment barrier. However, fate and toxicity of
      the metals in natural environments has to be assessed also by complexation
      capacity of NOM.

PMID- 18083214
TI  - A new middle Miocene pliopithecid from Inner Mongolia, China.

PMID- 18083216
TI  - Comparative temporal ecotoxicological study in a river basin influenced by
      petrochemical industries.
AB  - An approach was developed to evaluate ecotoxicological effects in river basins
      impacted by anthropic industrial discharges. Genotoxicity was the first level of
      evaluation of the river water, but when cytotoxicity was associated with
      genotoxic effects, our research group added chronic assays allowing the
      assessment of the ontogenic cycle in environmental diagnosis. The genotoxicity of
      river water sampled during two periods was compared using the microscreen phage
      induction and Salmonella/microsome assays. The study assessed the ability of
      these assays to diagnose environmental quality in an area where petrochemical
      impacts occur. The study was performed at six sampling sites using the
      Salmonella/microsome assay for 10 sampling periods and the microscreen phage
      induction assay for 15 samplings. The percentage of mutagenic activity was higher
      at the sites sampled in front of the petrochemical complex in both periods, but
      there were more significant mutagenic responses in the first assessment. However,
      comparing the percentages of samples with mutagenic and cytotoxic activity
      observed during the two periods it becomes clear that there are more cytotoxic
      samples during the second period throughout the area studied. The genotoxic
      activity analyzed by the microscreen phage-induction assay was constant in the
      second period. Chronic toxicity studies with the microcrustacean Daphnia magna
      confirm the toxic effects observed. The mortality of individuals was higher at
      the site most influenced by the petrochemical complex, followed by the station
      located upstream from this area, while the formation of ephippial eggs was
      uniform at all stations. The rise in the toxic potential of the region detected
      by cytotoxic and chronic toxicity may interfere and probably impair the use of
      the Salmonella/microsome assay to determine the potential of the area, showing
      the importance of assay association to evaluate potentially contaminated areas.

PMID- 18083215
TI  - Characterization of intrinsic and extrinsic risk factors for celery allergy in
      immunosenescence.
AB  - Recent studies indicated an underestimation of allergies in elderly. In our
      experimental food allergy model of protein feeding under acid-suppression we
      aimed to assess whether food allergy can be induced in immunosenescent mice.
      Furthermore, the impact of gastric digestion on celery allergenicity was
      evaluated in aged patients. Measurements of serum zinc and iron levels in
      senescent and adult BALB/c mice for definition of the nutritional status
      indicated a possible alteration of the immune response in the aged animals due to
      reduced zinc and iron levels. Feedings of mice with digestion-sensitive celery
      proteins under physiological gastric conditions induced IgG1 and IgG2a in the
      aged and preferentially IgG1 in the adult animals. In contrast, incomplete
      digestion due to acid-suppression rendered celery-specific IgE, positive skin
      tests and elevated IL-5 levels in both age groups. Also in aged celery allergic
      patients (mean age 72 years) properly digested celery showed decreased capacity
      to bind and crosslink IgE as evaluated by skin tests and IgE immunoblot. Thus, in
      the geriatric murine model, celery allergy was induced only if gastric digestion
      was hindered. Accordingly, gastric proteolysis decreased in vitro and in vivo IgE
      reactivity against celery proteins in aged allergic patients.

PMID- 18083217
TI  - Prevention strategies in palmar-plantar erythrodysesthesia onset: the role of
      regional cooling.
AB  - OBJECTIVE: Palmar-plantar erythrodysesthesia (PPE) is a characteristic cutaneous
      toxicity associated with pegylated liposomal doxirubicin (PLD). Different
      therapies have been proposed to alleviate PPE onset. We performed a prospective
      study to evaluate preventive strategies to reduce PPE incidence in patients
      treated for gynecologic cancers. METHODS: Fifty-three patients were treated from
      2001 to 2006 with PLD as single agent therapy or in combination with carboplatin
      or paclitaxel. PLD dosages were in the range of 30-50 mg/m2 every 21-28 days. All
      patients received premedication with dexamethasone and pyridoxine. Twenty-eight
      patients received application of ice packs on extremities during PLD infusion.
      RESULTS: PPE was observed in 11 patients (20.8%). PLD administration as single
      agent or in combination and schedule of PLD therapy did not affect PPE incidence.
      A significant reduction in PPE onset was observed if PLD dosage was 30-35 mg/m2
      (p=0.03) and when patients were submitted to regional cooling protocol
      (p=0.0097). CONCLUSIONS: The use of ice packs around wrists and ankles is a
      simple and well tolerated prevention strategy and its efficacy is demonstrated in
      this study.

PMID- 18083218
TI  - Use of gene expression profiles to stage concurrent endometrioid tumors of the
      endometrium and ovary.
AB  - OBJECTIVE: The objectives of this study were to determine whether there are
      distinct gene expression profiles for endometrial and ovarian endometrioid
      carcinomas and to create a statistical model using these profiles to predict
      their organ of origin. METHODS: Expression profiles of seven stage I, grades 1
      and 2, endometrioid endometrial carcinomas and seven stage I ovarian endometrioid
      carcinomas were analyzed as the training set. The test set included seven
      advanced endometrial carcinomas and nine dual primary endometrial and ovarian
      primary tumors of endometrioid histology. Unsupervised hierarchical clustering,
      multidimensional scaling (MDS) and predictive analysis of microarrays (PAM) were
      used to analyze the data. RESULTS: We identified 163 differentially expressed
      (DE) genes between endometrial and ovarian tumors. Both unsupervised hierarchical
      clustering and multidimensional scaling showed clear separation of the two
      groups. Pathway analysis of the 163 DE genes revealed significant biological
      differences between the two groups, which included metabolic and biosynthetic
      pathways. Further classification analysis on the training data using predictive
      analysis of microarray generated a 119-gene predictive model with 100% cross
      validation accuracy. When the 119-gene model was applied to the test set of 16
      samples, we found concordance in 11/16 samples and discordance in 5/16 samples
      with the pathologic classification. CONCLUSION: We conclude that, although
      similar in histologic appearance, endometrioid carcinomas of the ovary and
      endometrium have distinct gene expression patterns. A larger test set is needed
      to prospectively evaluate this prediction model further.

PMID- 18083219
TI  - Non-genomic actions of estrogens and their interaction with genomic actions in
      the brain.
AB  - Ligands for the nuclear receptor superfamily have at least two mechanisms of
      action: (a) classical transcriptional regulation of target genes (genomic
      mechanisms); and (b) non-genomic actions, which are initiated at the cell
      membrane, which could also impact transcription. Though transcriptional
      mechanisms are increasingly well understood, membrane-initiated actions of these
      ligands are incompletely understood. This has led to considerable debate over the
      physiological relevance of membrane-initiated actions of hormones versus genomic
      actions of hormones, with genomic actions predominating in the endocrine field.
      There is good evidence that the membrane-limited actions of hormones,
      particularly estrogens, involve the rapid activation of kinases and the release
      of calcium and that these are linked to physiologically relevant scenarios in the
      brain. We show evidence in this review, that membrane actions of estrogens, which
      activate these rapid signaling cascades, can also potentiate nuclear
      transcription in both the central nervous system and in non-neuronal cell lines.
      We present a theoretical scenario which can be used to understand this
      phenomenon. These signaling cascades may occur in parallel or in series but
      subsequently, converge at the modification of transcriptionally relevant
      molecules such as nuclear receptors and/or coactivators. In addition, other non
      cognate hormones or neurotransmitters may also activate cascades to crosstalk
      with estrogen receptor-mediated transcription, though the relevance of this is
      less clear. The idea that coupling between membrane-initiated and genomic actions
      of hormones is a novel idea in neuroendocrinology and provides us with a unified
      view of hormone action in the central nervous system.

PMID- 18083220
TI  - Motives for risk-taking in adolescence: a cross-cultural study.
AB  - Most research on adolescent risk-taking has been conducted in Western societies,
      but it is as yet unknown whether motives to engage in risk behaviours show
      cultural variety. This study sets out to investigate differences in perceived
      motives to engage in perceived risks in Turkish and Welsh samples of young people
      (N=922) between 14 and 20 years of age. For this, a measurement scale to assess
      motives for risk-taking was constructed and validated cross-culturally. The scale
      was based on Kloep and Hendry's [(1999). Challenges, risks and coping in
      adolescence. In D. Messer, & S. Millar (Eds.), Exploring developmental psychology
      (pp. 400-416). London: Arnold] theoretical framework and the results of a study
      by Guney and Cok [(2006). Adolescent risk-taking: Calculated risks, Turkish
      experience. In Paper presented at the 10th Bi-annual conference of the European
      Association for Research on Adolescence, Antalya, Turkey]. Results show that
      different motives are associated with different risk behaviours, confirming Kloep
      and Hendry's expanded model. There were small, but significant, national
      differences, implying that motives to take risks-as opposed to actual risks taken
      could be similar across adolescent populations, independent of culture.

PMID- 18083221
TI  - The link between emotion identification skills and socio-emotional functioning in
      early adolescence: a 1-year longitudinal study.
AB  - Amongst adults, low emotion identification skill (EIS) relates to poor emotion
      regulation strategies, higher rates of anxiety and depression, and higher rates
      of somatic illness and disease [Taylor, G. J., & Bagby, R. M. (2004). New trends
      in alexithymia research. Psychotherapy and Psychosomatics, 73, 68-77]. Little
      research has examined EIS in adolescence and, in particular, the longitudinal
      impact of EIS on social support and affective experience. Six hundred and sixty
      seven high school students completed measures of EIS, social support and positive
      and negative affects in Grade 8, and again in Grade 9. Repeated measure ANOVAS
      revealed that negative affect increased and positive affect decreased from Grades
      8 to 9. Structural equation modelling revealed that low EIS predicted increases
      in fear, decreases in positive affect, and decreases in the quality and quantity
      of social support. Amongst boys, low EIS also predicted increases in sadness. We
      discuss the implications of these findings for early prevention programmes.

PMID- 18083222
TI  - Classroom climate indicators and attitudes towards foreigners.
AB  - The school has been described as an important socialization agent in the process
      of political development. But the mechanism concerning how school contributes to
      political development has rarely been investigated. In this study we focus on
      contextual variables, i.e., classroom climate indicators that are seen as
      important aspects of the context in which adolescent development takes place. The
      study was based on the total of 1312 German students. In multilevel analyses, we
      regressed students' reports on intolerant attitudes towards foreigners on
      background characteristics as well as on the perceived classroom climate.
      Fairness in the classroom as perceived by the individual student was found to be
      negatively related to intolerance and achievement pressure was positively
      related. Students attending the high college-bound track reported less
      antiforeigner attitudes as did students where parents had a more sophisticated
      educational background. The results are discussed proposing schools to provide an
      open climate as a contextual framework for the development of tolerant attitudes
      among adolescents.

PMID- 18083223
TI  - Biodegradable poly-beta-hydroxybutyrate scaffold seeded with Schwann cells to
      promote spinal cord repair.
AB  - Cavity formation is an important obstacle impeding regeneration after spinal cord
      injury and bridging strategies are essential to provide physical substrate
      allowing axons to grow across the lesion site. In this study we evaluated effects
      of biodegradable tubular conduit made from poly-beta-hydroxybutyrate (PHB)
      scaffold with predominantly unidirectional fiber orientation and supplemented
      with cultured adult Schwann cells on axonal regeneration after cervical spinal
      cord injury in adult rats. After transplantation into the injured spinal cord,
      plain PHB conduit was well-integrated into posttraumatic cavity and induced
      modest astroglial reaction. Regenerating axons were found mainly outside the PHB
      with only single fibers crossing the host-graft interface. No host Schwann cells
      migrated into the graft. In contrast, when suspension of adult Schwann cells was
      added to the PHB during transplantation, neurofilament-positive axons filled the
      conduit and became associated with the implanted cells. Although rubrospinal
      fibers did not enter the PHB, numerous raphaespinal and CGRP-positive axons were
      found within the conduit. Modification of PHB surface with fibronectin, laminin
      or collagen significantly increased Schwann cell attachment and proliferation in
      vitro. However, transplantation of PHB conduit pre-coated with fibronectin and
      seeded with Schwann cells did not alter axonal growth response. The results
      demonstrate that a PHB scaffold promotes attachment, proliferation and survival
      of adult Schwann cells and supports marked axonal regeneration within the graft.

PMID- 18083224
TI  - The effect of crosslinking heparin to demineralized bone matrix on mechanical
      strength and specific binding to human bone morphogenetic protein-2.
AB  - Demineralized bone matrix (DBM) is a collagen-based scaffold, but its low
      mechanical strength and limited BMP-2 binding ability restrict its application in
      bone repair. It is known that heparin could be immobilized onto scaffolds to
      enhance their binding of growth factors with the heparin-binding domain. Here, we
      crosslinked heparin to DBM to increase its BMP-2 binding ability. To our
      surprise, the mechanical strength of DBM was also dramatically increased. The
      compression modulus of heparin crosslinked DBM (HC-DBM) have improved (seven-fold
      increased) under wet condition, which would allow the scaffolds to keep specific
      shapes in vivo. As expected, HC-DBM showed specific binding ability to BMP-2.
      Additional studies showed the bound BMP-2 exerted its function to induce cell
      differentiation on the scaffold. Subcutaneous implantation of HC-DBM carrying BMP
      2 showed higher alkaline phosphatase (ALP) activity (2 weeks), more calcium
      deposition (4 and 8 weeks) and more bone formation than that of control groups.
      It is concluded that HC-DBM has increased mechanical intensity as well as
      specific BMP-2 binding ability; HC-DBM/BMP-2 enhances the osteogenesis and
      therefore could be an effective medical device for bone repair.

PMID- 18083225
TI  - Covalent functionalization of NiTi surfaces with bioactive peptide amphiphile
      nanofibers.
AB  - Surface modification enables the creation of bioactive implants using traditional
      material substrates without altering the mechanical properties of the bulk
      material. For applications such as bone plates and stents, it is desirable to
      modify the surface of metal alloy substrates to facilitate cellular attachment,
      proliferation, and possibly differentiation. In this work we present a general
      strategy for altering the surface chemistry of nickel-titanium (NiTi) shape
      memory alloy in order to covalently attach self-assembled peptide amphiphile (PA)
      nanofibers with bioactive functions. Bioactivity in the systems studied here
      includes biological adhesion and proliferation of osteoblast and endothelial cell
      types. The optimized surface treatment creates a uniform TiO(2) layer with low
      levels of Ni on the NiTi surface, which is subsequently covered with an
      aminopropylsilane coating using a novel, lower temperature vapor deposition
      method. This method produces an aminated surface suitable for covalent attachment
      of PA molecules containing terminal carboxylic acid groups. The functionalized
      NiTi surfaces have been characterized by X-ray photoelectron spectroscopy (XPS),
      time-of-flight secondary ion mass spectroscopy (ToF-SIMS), and atomic force
      microscopy (AFM). These techniques offer evidence that the treated metal surfaces
      consist primarily of TiO(2) with very little Ni, and also confirm the presence of
      the aminopropylsilane overlayer. Self-assembled PA nanofibers presenting the
      biological peptide adhesion sequence Arg-Gly-Asp-Ser are capable of covalently
      anchoring to the treated substrate, as demonstrated by spectrofluorimetry and AFM
      techniques. Cell culture and scanning electron microscopy (SEM) demonstrate
      cellular adhesion, spreading, and proliferation on these functionalized metal
      surfaces. Furthermore, these experiments demonstrate that covalent attachment is
      crucial for creating robust PA nanofiber coatings, leading to confluent cell
      monolayers.

PMID- 18083226
TI  - IFPA award in placentology lecture - characteristics and significance of
      trophoblast giant cells.
AB  - Extraembryonic development in rodents depends on the differentiation and function
      of trophoblast giant cells. Morphologically striking, giant cells exhibit many
      extraordinary characteristics adapted to ensure the success of pregnancy. This
      review summarizes some of the intriguing aspects of giant cell morphology and
      function. Giant cells are highly polyploid as a result of a switch from a mitotic
      to an endoreduplicative cell cycle. They further partition their genome content
      into various fragments which may represent a mechanism to maximize protein
      synthesis. Similar to metastatic tumour cells, they breach basement membranes and
      invade deeply into a foreign tissue, the maternal decidualized uterine stroma.
      Their angiogenic and vasodilatory properties, combined with the ability to
      remodel arterial walls, enable them to redirect maternal blood flow towards the
      implantation site. Recent advances have recognized that the giant cell population
      is more diverse than previously recognized and future studies will have to show
      how these subtypes differ functionally and how their differentiation is
      controlled.

PMID- 18083227
TI  - Regulation of trophoblast invasion - a workshop report.
AB  - Trophoblast invasion during placental development helps to establish efficient
      physiological exchange between maternal and fetal circulatory systems.
      Trophoblast stem cells differentiate into multiple subtypes, including some that
      are highly invasive. Signalling to the trophoblast from decidua, uterine natural
      killer cells and vascular smooth muscle can regulate extravillous trophoblast
      differentiation. Important questions remain about how these cellular interactions
      promote trophoblast invasion and the signalling pathways that are involved. New
      and established biological models are being used to experimentally examine these
      interactions and the underlying molecular mechanisms.

PMID- 18083229
TI  - Alkylating agents induce activation of NFkappaB in multiple myeloma cells.
AB  - Multiple myeloma is still not curable and drug combination strategies are
      currently being evaluated in order to achieve high remission rates with tolerable
      toxicity. Bortezomib has been shown to exert inhibitory effects on NFkappaB
      activity. NFkappaB in turn is known to be activated by cytokines, growth factors
      and by cellular adhesion to bone marrow stromal cells and represents an important
      mediator of primary and secondary drug resistance in multiple myeloma that
      confers to proliferation and survival. In this study we confirm that bortezomib
      sensitized MM cells to the DNA-damaging drugs melphalan and doxorubicin. Further,
      we demonstrate that the sole incubation of MM cells with melphalan or doxorubicin
      leads to a vast activation of NFkappaB activity. Additionally, we show that the
      co-incubation of bortezomib with melphalan or doxorubicin reduces activation of
      NFkappaB. These data suggest that the drug-sensitizing effect of bortezomib on MM
      cells is due to inhibition of melphalan- and doxorubicin-induced activation of
      NFkappaB activity. This study, therefore, supports the idea of combining a
      NFkappaB inhibitor with alkylating drugs in the therapy of multiple myeloma.

PMID- 18083228
TI  - Response of primary plasma cell leukemia to the combination of bortezomib and
      dexamethasone: do specific cytogenetic and immunophenotypic characteristics
      influence treatment outcome?
AB  - Plasma cell leukemia (PCL) is a rare and aggressive form of plasma cell
      dyscrasias. Its special biological characteristics may play an important role in
      the poor outcome when treated with conventional therapy or even with stem cell
      transplantation. New treatment approaches based on the biology of this disease
      are mandatory. Here we present three cases of primary PCL with adverse
      cytogenetics (deletion 13q14 and translocation 4;14) and specific
      immunophenotypic features (CD27 antigen strong expression) in which excellent
      response and sustained remission was achieved with the combination of bortezomib
      and dexamethasone. The possible role of these biological characteristics is been
      analyzed.

PMID- 18083231
TI  - Rate of removal of bird carcasses in arable farmland by predators and scavengers.
AB  - Studies requiring carcasses to be retrieved to detect mortality and its causes in
      wildlife can be difficult to interpret due to removal of carcasses by scavengers.
      This paper describes two linked studies measuring rate of removal of carcasses
      from farmland in the UK, carried out to inform the results of a pesticide study
      involving carcass searching. In winter, 6% of carcasses had been removed 24 h
      after placement, and 32% had been removed 96 h after placement; wild bird
      carcasses were removed significantly faster than those of artificially reared
      birds. In summer, 76% of carcasses had been removed 24 h after placement and 91%
      after 96 h. A literature review of similar studies is given. Carcass removal
      rates by predators and scavengers appear to vary widely between sites and
      seasons, and may be high. If the results of studies involving carcass searches or
      surveillance are to be interpreted correctly, carcass removal rate by scavengers
      should be measured under similar conditions to, and contemporaneous with, those
      under which mortality is expected to occur.

PMID- 18083230
TI  - Imatinib-resistant K562 cells are more sensitive to celecoxib, a selective COX-2
      inhibitor: role of COX-2 and MDR-1.
AB  - Selective inhibition of the BCR/ABL tyrosine kinase by imatinib (STI571,
      Glivec/Gleevec) is the therapeutic strategy in patients with chronic myelogenous
      leukemia (CML). Despite significant hematologic and cytogenetic responses with
      imatinib, mainly due to the mutations in the Abl kinase domain, resistance occurs
      in patients with advanced disease. In the present study on imatinib-resistant
      K562 cells (IR-K562), however, no such mutations in the Abl kinase domain were
      observed. Further studies revealed the over-expression of COX-2 and MDR-1 in IR
      K562 cells suggesting the possible involvement of COX-2 in the development of
      resistance to imatinib. So, we sought to examine the effect of celecoxib, a
      selective COX-2 inhibitor, on IR-K562 cells. The results clearly indicate that
      celecoxib is more effective in IR-K562 cells with a lower IC50 value of 10 microM
      compared to an IC50 value of 40 microM in K562 cells. This increase in the
      sensitivity of IR-K562 cells towards celecoxib suggests that the development of
      resistance in IR-K562 cells is COX-2 dependent. Further studies revealed down
      regulation of MDR-1 by celecoxib and a decline in p-Akt levels. Celecoxib-induced
      apoptosis of IR-K562 cells led to release of cytochrome c, PARP cleavage and
      decreased Bcl2/Bax ratio. Also, celecoxib at 1 microM concentration induced
      apoptosis in IR-K562 cells synergistically with imatinib by reducing the IC50
      value of imatinib from 10 to 6 microM. In conclusion, the present study indicates
      over-expression of COX-2 and MDR-1 in IR-K562 cells and celecoxib, a COX-2
      specific inhibitor, induces apoptosis by inhibiting COX-2 and down-regulating MDR
      1 expression through Akt/p-Akt signaling pathway.

PMID- 18083233
TI  - The use of molecular techniques to characterize the microbial communities in
      contaminated soil and water.
AB  - Traditionally, the identification and characterization of microbial communities
      in contaminated soil and water has previously been limited to those
      microorganisms that are culturable. The application of molecular techniques to
      study microbial populations at contaminated sites without the need for culturing
      has led to the discovery of unique and previously unrecognized microorganisms as
      well as complex microbial diversity in contaminated soil and water which shows an
      exciting opportunity for bioremediation strategies. Nucleic acid extraction from
      contaminated sites and their subsequent amplification by polymerase chain
      reaction (PCR) has proved extremely useful in assessing the changes in microbial
      community structure by several microbial community profiling techniques. This
      review examines the current application of molecular techniques for the
      characterization of microbial communities in contaminated soil and water.
      Techniques that identify and quantify microbial population and catabolic genes
      involved in biodegradation are examined. In addition, methods that directly link
      microbial phylogeny to its ecological function at contaminated sites as well as
      high throughput methods for complex microbial community studies are discussed.

PMID- 18083232
TI  - cDNA cloning and expression analysis of Eisenia fetida (Annelida: Oligochaeta)
      phytochelatin synthase under cadmium exposure.
AB  - Metallothioneins (MTs) are central to trace metal homeostasis and detoxification
      throughout biological systems. Prokaryotes, plants, and fungi utilize both gene
      encoded cysteine-rich polypeptides (classically designated Class I and II MTs)
      and enzymatically synthesized cysteine-rich peptides (classically designated
      Class III MTs or phytochelatins). In contrast, although gene encoded MTs are
      ubiquitous in animal species the identification of a functional phytochelatin
      synthase in the nematode Caenorhabditis elegans, a representative member of the
      Ecdysozoa, provided the first evidence for these metal-binding peptides in
      animals. By exploiting the conservation observed between species we have been
      able to clone and transcriptionally characterize a phytochelatin synthase from
      the immune cells of the earthworm Eisenia fetida, the first evidence for its
      presence in a phylum belonging to the Lophototrochozoa. The complete coding
      sequence of this enzyme was determined and the phylogenetic relationship to
      plant, yeast and nematode enzymes elucidated. Temporal- and dose-profiling of the
      transcriptional regulation of phytochelatin synthase and MT in response to
      cadmium was performed by using real-time PCR.

PMID- 18083235
TI  - Chronic bacterial prostatitis and relapsing Enterococcus faecalis bacteraemia
      successfully treated with moxifloxacin.

PMID- 18083234
TI  - Functional interaction of AIRE with PIAS1 in transcriptional regulation.
AB  - AIRE (autoimmune regulator) promotes the establishment of self-tolerance by
      regulating gene expression in the thymus. Mutations in AIRE lead to an autoimmune
      disease, APECED. Here we have identified PIAS proteins as novel AIRE interaction
      partners. Although PIAS proteins function as E3 SUMO ligases, AIRE is not
      sumoylated. We expressed AIRE, wt PIAS1, and PIAS1 mutants with deleted SP-RING
      domain or SUMO interaction motif (SIM) in different cell lines and demonstrate
      that AIRE and PIAS1 localize to adjacent nuclear bodies (NBs). The expression of
      AIRE enhances the formation of PIAS1 NBs. The ability of PIAS1 to localize into
      NBs and interconnect with AIRE is neither dependent on the SP-RING domain nor the
      SIM. Further, we show that PIAS1 is able to attract AIRE into SUMO1-containing
      complexes and that the process is dependent on the SIM of PIAS1. PIAS1 and AIRE
      concurrently activate the human insulin promoter, a known target gene of AIRE,
      and the SP-RING is required for this activation. Moreover, AIRE represses and
      PIAS1 activates the CSTB promoter, used as a model for a housekeeping promoter,
      and both the SP-RING and SIM are needed for its activation by PIAS1.
      Collectively, our data suggest that AIRE and PIAS1 interact functionally to
      regulate the activities of the target genes of AIRE.

PMID- 18083237
TI  - Automated characterization of multiple alpha peaks in multi-site
      electroencephalograms.
AB  - The identification of alpha rhythm in the human electroencephalogram (EEG) is
      generally a laborious task involving visual inspection of the spectrum. Moreover
      the occurrence of multiple alpha rhythms is often overlooked. This paper seeks to
      automate the process of identifying alpha peaks and quantifying their frequency,
      amplitude and width as a function of position on the scalp. Experimental EEG was
      fitted with parameterized spectra spanning the alpha range, with results
      categorized by multi-site criteria into three distinct classes: no
      distinguishable alpha peak, a single alpha peak, and two alpha peaks. The
      technique avoids visual bias, integrates spatial information, and is automated.
      We show that multiple alpha peaks are a common feature of many spectra.

PMID- 18083236
TI  - Simultaneous nitric oxide and dehydroascorbic acid imaging by combining
      diaminofluoresceins and diaminorhodamines.
AB  - Spatial measurements of nitric oxide (NO) production are important to understand
      the function and metabolism of this molecule. The reagent, 4,5-diaminofluorescein
      (DAF-2) and several structurally similar probes are widely used for detection and
      imaging of NO. However, DAF-2 also reacts with dehydroascorbic acid (DHA) in
      biological samples, with both products having nearly indistinguishable
      fluorescence spectra. Measurements using fluorimetry and fluorescence microscopy
      cannot easily differentiate NO-related fluorescent signals from DHA-related
      signals. While DAFs and the structurally related diaminorhodamines (DARs) both
      react with NO and DHA, they do so to different extents. We report a
      multiderivatization method to image NO and DHA simultaneously by using both DAF
      and DAR. Specifically, DAF-2 and DAR-4M are used to image NO and DHA
      concentrations; after reaction, the solutions are excited, at 495 nm to measure
      fluorescence emission from DAF-2, and at 560 nm to measure fluorescence emission
      from DAR-4M. Using the appropriate calibrations, images are created that depend
      either on the relative NO or the relative DHA concentration, even though each
      probe reacts to both compounds. The method has been validated by imaging NO
      production in both undifferentiated and differentiated pheochromocytoma (PC12)
      cells.

PMID- 18083238
TI  - The Violence Risk Scale Second Edition (VRS-2) as a predictor of institutional
      violence in a British forensic inpatient sample.
AB  - This study examined the utility of The Violence Risk Scale 2nd Edition (VRS-2)
      [Wong, S., Gordon, A., 1999. Manual for the Violence Risk Scale. University of
      Saskatchewan, Saskatchewan, Canada] as an institutional violence risk predictor.
      The VRS-2 and the Psychopathy Checklist: Screening Version (PCL: SV) were rated
      independently from pre-admission/admission case records in 147 patients in a
      medium security facility. Inpatient aggression post-admission was recorded by an
      independent researcher. Aggressive patients had significantly higher scores on
      both measures. The VRS-2 and the PCL: SV were only modest predictors of inpatient
      aggression. The VRS-2 putative "dynamic" items showed the highest predictive
      accuracy. The results tentatively support the use of the VRS-2 as a predictor of
      inpatient violence in mentally ill patients in medium security settings, with the
      dynamic component of this instrument showing most promise. Further studies
      validating this instrument are required before it is adopted into routine
      clinical practice.

PMID- 18083239
TI  - Analysis of capturing skin antigens in the steady state using milk fat globule
      EGF factor 8-deficient skin-hyperpigmented mice.
AB  - Dendritic cells (DCs) can capture apoptotic cells and present them to immune
      competent cells as self-antigens (Ags). Langerhans cells (LCs), DCs in the
      epidermis, are capable of presenting tissue-associated Ags in the steady state,
      suggesting that LCs may also capture apoptotic cells and transport them to skin
      regional lymph nodes (LNs). However, to what extent LCs utilize apoptotic cells
      as self-Ags in vivo is still unclear. To clarify this point, we examined the
      contribution of milk fat globule EGF factor 8 (MFG-E8), a secreted glycoprotein,
      to capturing skin Ags. MFG-E8 is expressed in several subsets of macrophages (M
      phi s) and DCs, including LCs, and crucial for recognizing and engulfing
      apoptotic cells. Using a skin-hyperpigmented KRT14-Kitl-Tg (Kitl-Tg) mouse
      system, we measured the accumulation of melanin granules (MGs), a marker of skin
      Ags, transported from the skin to regional LNs in Mfge8-deficient mice.
      Unexpectedly, their accumulation in Mfge8-deficient Kitl-Tg mice was comparable
      to that in Mfge8-heterozygous littermates. Mfge8-deficient DCs engulfed skin
      derived MGs efficiently in vitro. The results indicate that MFG-E8 does not
      contribute critically or functions redundantly to capturing and trafficking of
      skin Ags in the steady state, and suggest a possibility that LCs may capture skin
      Ags in forms other than apoptotic cells in vivo.

PMID- 18083240
TI  - TNF and sTNFR1/2 plasma levels in ALS patients.
AB  - The involvement of the immune system has been hypothesized in the pathogenesis of
      amyotrophic lateral sclerosis (ALS). In this study a significantly higher level
      of TNF-alpha and its soluble receptors, TNF-R1 and TNF-R2, has been found in
      plasma of patients affected by the sporadic form of ALS compared to normal
      subjects. The genetic analysis of the polymorphisms of TNF-alpha, TNF-R1 and TNF
      R2 showed no statistically significant differences in alleles and genotype
      frequencies between patients and controls. These data suggest a participation of
      the immune system in response to as far unknown intracellular signals.

PMID- 18083241
TI  - The VIZIER project: preparedness against pathogenic RNA viruses.
AB  - Life-threatening RNA viruses emerge regularly, and often in an unpredictable
      manner. Yet, the very few drugs available against known RNA viruses have
      sometimes required decades of research for development. Can we generate
      preparedness for outbreaks of the, as yet, unknown viruses? The VIZIER (VIral
      enZymes InvolvEd in Replication) (http://www.vizier-europe.org/) project has been
      set-up to develop the scientific foundations for countering this challenge to
      society. VIZIER studies the most conserved viral enzymes (that of the replication
      machinery, or replicases) that constitute attractive targets for drug-design. The
      aim of VIZIER is to determine as many replicase crystal structures as possible
      from a carefully selected list of viruses in order to comprehensively cover the
      diversity of the RNA virus universe, and generate critical knowledge that could
      be efficiently utilized to jump-start research on any emerging RNA virus. VIZIER
      is a multidisciplinary project involving (i) bioinformatics to define functional
      domains, (ii) viral genomics to increase the number of characterized viral
      genomes and prepare defined targets, (iii) proteomics to express, purify, and
      characterize targets, (iv) structural biology to solve their crystal structures,
      and (v) pre-lead discovery to propose active scaffolds of antiviral molecules.

PMID- 18083242
TI  - Altered emotionality, spatial memory and cholinergic function in caveolin-1 knock
      out mice.
AB  - Neurological phenotypes associated with loss of caveolin 1 (cav-1) (the defining
      structural protein in caveolar vesicles, which regulate signal transduction and
      cholesterol trafficking in cells) in mice have been reported recently. In brain,
      cav-1 is highly expressed in neurons and glia. We investigated emotional and
      cognitive behavioural domains in mice deficient in cav-1 (CavKO mice). CavKO mice
      were more anxious and spent more time in self-directed grooming behaviour than
      wild-type (wt) mice. In a spatial/working memory task, CavKO mice failed to
      recognize the object displacement, thus showing a spatial memory impairment.
      CavKO mice showed higher locomotor activity than wt mice, thus suggesting reduced
      inhibitory function by CNS cholinergic systems. Behavioural response to the
      cholinergic muscarinic antagonist, scopolamine (2 mg/Kg), was decreased in CavKO
      mice. Few behavioural sex differences emerged in mice; whereas the sex
      differences were generally attenuated or even reverted in the null genotype. Our
      data confirm a distinct behavioural phenotype in CavKO mice and indicate a
      selective alteration in central cholinergic function.

PMID- 18083243
TI  - Gene expression profiling reveals decreased expression of two hemoglobin genes
      associated with increased consumption of oxygen in Chironomus tentans exposed to
      atrazine: a possible mechanism for adapting to oxygen deficiency.
AB  - Atrazine is an extensively used triazine herbicide in agricultural and
      residential areas and has been routinely detected in many surface and ground
      waters. This study reveals various up- and down-regulated genes associated with
      hypoxic stress in atrazine-treated fourth-instar Chironomus tentans larvae
      (midges) by using restriction fragment differential display-PCR. Two down
      regulated hemoglobin cDNAs were isolated from the midges. Northern blot analysis
      indicated CteHb-IIbeta and CteHb-III mRNA expressions decreased by 36 and 21%,
      respectively, in midges exposed to atrazine at 1 microg/L for 96h. Decreased
      hemoglobin gene expression was associated with elevated oxygen consumption in
      atrazine-treated midges. Midges exposed to atrazine at 1 microg/L increased their
      oxygen consumption by 47%, whereas midges exposed to atrazine at 1000 microg/L
      for 48h increased their oxygen consumption by 66%. Our study demonstrates for the
      first time that atrazine, at environmentally relevant concentrations, can elevate
      respiration, possibly eliciting counteractive measures at the transcriptional
      level to adapt to oxygen deficiency in an ecologically important aquatic insect.
      Our results further suggest that the ability to modulate both the quantity and
      quality of Hb serves as an adaptive response to counteract the initial onset of
      oxygen deficiency induced by atrazine in midges.

PMID- 18083244
TI  - Physiological responses of Ulva pertusa and U. armoricana to copper exposure.
AB  - A comparative study of copper (Cu) toxicity and tolerance in two species of Ulva
      from Korea, the native Ulva pertusa and alien Ulva armoricana, was conducted by
      examining the effects on growth, pigmentation, chlorophyll fluorescence,
      antioxidant capacity and nitrate reductase activity. Toxic effects of Cu were
      less expressed in U. armoricana than in U. pertusa. At lower concentrations (25
      50 microgL(-1)), exposure to Cu did not affect thallus growth of U. armoricana,
      whilst growth was significantly reduced in U. pertusa. An increase in chlorophyll
      concentrations was observed in U. armoricana exposed up to 100 microgL(-1),
      whereas Cu caused a significant chlorophyll reduction in U. pertusa. Chlorophyll
      b was reduced to a lesser extent than chlorophyll a by higher Cu concentrations.
      In U. armoricana, the maximum efficiency of photosystem II, minimum fluorescence,
      maximum electron transport rate and non-photochemical quenching were unaffected
      by Cu except at the highest concentration tested. U. pertusa showed a significant
      decrease in those parameters at much lower Cu concentrations. It was notable that
      in this alga the maximum efficiency of photosystem II was reduced at higher Cu
      concentrations than relative electron transport rate. Elevated concentrations of
      Cu induced a strong activation of antioxidant activity in U. armoricana, whereas
      the generation of high levels of reactive oxygen species probably decreased the
      non-enzymatic antioxidant defense system in U. pertusa. An increase in the
      nitrate reductase activity of U. armoricana at 50-100 microgL(-1) Cu coincided
      with the increase in chlorophyll contents, whereas U. pertusa showed a
      significant decrease at the higher Cu concentration. Differences in the
      sensitivity of the two species of Ulva to Cu may influence their competitive
      interactions in Korean coastal waters experiencing temporal increases in the
      loading of heavy metals.

PMID- 18083245
TI  - Humic substances modify accumulation but not biotransformation of pyrene in
      salmon yolk-sac fry.
AB  - Humic substances may influence the bioavailability of polycyclic aromatic
      hydrocarbons (PAHs) in aquatic environment. Relatively little is known how humic
      substances affect the biotransformation of PAHs in aquatic animals. Here we
      report how two different types of humic substances affected the accumulation of
      pyrene, a four-ringed PAH, to yolk-sac fry of landlocked salmon (Salmo salar m.
      sebago). The accumulation of pyrene to yolk-sac fry tissues was inversely related
      to humic substance concentration in a short term (72h) exposure. However, the
      biotransformation of pyrene was not affected by humic substances. Pyrene or humic
      substances did not induce CYP1A activity in yolk-sac fry tissues contrasting to
      beta-naphthoflavone, which was used as a positive control. Yolk-sac fry were
      capable to biotransform pyrene to phase I (1-hydroxypyrene) and phase II (pyrene
      1-sulphate) products. Interestingly, glucuronide conjugate (i.e. pyrene-1
      glucuronide) was not present in yolk-sac fry tissues. The concentration of parent
      pyrene and 1-hydroxypyrene remained the same throughout the experiment but the
      concentration of pyrene-1-sulphate more than doubled from 24 to 72h. This finding
      suggests that salmon yolk-sac fry are not capable to excrete phase II
      biotransformation products or the excretion is very slow. Further, this could
      indicate that early life stage toxicity of many CYP1A inducing compounds is
      related to accumulation of phase II conjugates in fry tissues.

PMID- 18083246
TI  - Divergence of trypanothione-dependent tryparedoxin cascade into cytosolic and
      mitochondrial pathways in arsenite-resistant variants of Leishmania amazonensis.
AB  - Evidences are presented in the in vivo study that overexpression of tryparedoxin
      peroxidases (TXNPxs) diverged into cytosolic pathway in arsenite-resistant
      variant A and mitochondrial pathway in variant A' of Leishmania amazonensis is
      due to the upregulation of the corresponding upstream tryparedoxins (TXNs) in the
      cytosol as well as the mitochondrion respectively. Evidences are also presented
      that exposure of L. amazonensis to arsenite in the early hours led to the
      production of reactive oxygen species (ROS), which in turn induced the
      overexpression of the genes of both cytosolic and mitochondrial trypanothione
      dependent tryparedoxin pathway due probably to physiological and functional
      needs. The sequence of events leading to the upregulation indicates that
      cytosolic tryparedoxin pathway is upregulated earlier than that of mitochondrial
      tryparedoxin pathway. Based on the kinetics of gene upregulation of the cytosolic
      pathway is different from that of mitochondrial pathway, and cTXNPx and mTXNPx
      differentially detoxify H(2)O(2) and of t-butyl hydroperoxide respectively, it is
      postulated that during arsenite selection, different ROS species may have been
      overproduced in either variants A or A', leading to the divergence of the
      trypanothione-dependent tryparedoxin pathways in these variants.

PMID- 18083247
TI  - Haemozoin formation.
AB  - Formation of malaria pigment or haemozoin is the major route of haem
      detoxification in the malaria parasite Plasmodium falciparum as well as several
      other species of haematophagous organisms, including other Plasmodium species,
      helminth worms such as Schistosoma mansoni and blood-sucking insects such as
      Rhodnius prolixus. Recent advances in our understanding of the formation of
      haemozoin, both from new observations that it is formed within lipid bodies in P.
      falciparum and S. mansoni and biomimetic studies on the formation of its
      synthetic counterpart beta-haematin are reviewed. The review also covers methods
      available for screening compounds for their ability to inhibit beta-haematin
      formation.

PMID- 18083248
TI  - Molecular determinants of compatibility polymorphism in the Biomphalaria
      glabrata/Schistosoma mansoni model: new candidates identified by a global
      comparative proteomics approach.
AB  - The co-evolutionary dynamics that exist in host-parasite interactions sometimes
      lead to compatibility polymorphisms, the molecular bases of which are rarely
      investigated. To identify key molecules that are involved in this phenomenon in
      the Schistosoma mansoni/Biomphalaria glabrata model, we developed a comparative
      proteomics approach using the larval stages that interact with the invertebrate
      host. We used qualitative and quantitative analyses to compare the total
      proteomes of primary sporocysts from compatible and incompatible parasite
      strains. The differentially expressed proteins thus detected belong to three main
      functional groups: (i) scavengers of reactive oxygen species, (ii) components of
      primary metabolism, and (iii) mucin-like proteins. We discuss the putative roles
      played by these protein families as determinants of compatibility polymorphism.
      Since mucins are known to play key roles in the host-parasite interplay, we
      consider the newly discovered S. mansoni mucin-like proteins (SmMucin-like) as
      the most promising candidates for influencing the fate of host-parasite
      interactions. An analysis of their expression is presented in a paper published
      in the same journal issue.

PMID- 18083249
TI  - The relationship between physical condition and change in balance functions on
      exercise intervention and 12-month follow-up in Japanese community-dwelling older
      people.
AB  - The purposes of this study were to describe the change in balance functions of
      elderly people and to evaluate the relationship between physical conditions and
      changes in balance measurements after exercise intervention and 12-month follow
      up. One hundred and fifty-one subjects aged 60 and older practised exercise
      intervention for 3 months. The measurements of balance functions were one-legged
      standing with eyes open and closed (OLS-O, OLS-C), a functional reach test (FR),
      and a timed up and go test (TUG). The other measurements were maximum walking
      velocity, flexibility, and muscle strength. We evaluated the associations between
      the physical performance measurements and changes in the balance measurements.
      All the four balance measurements were significantly improved after intervention.
      The magnitude of the changes in OLS-O and FR after the intervention showed some
      negative correlations with the initial physical performance measurements, but OLS
      C showed some positive correlations. In addition, the changes in four balance
      measurements 12 months after the intervention showed some negative correlations
      to the physical measurements at post-investigation. These results suggested that
      specific approaches that adapt the task of balance training to the fitness level
      of each subject are needed to effectively improve the balance function of older
      people.

PMID- 18083251
TI  - Effects of ovariectomy and 17beta-estradiol treatment on the renin-angiotensin
      system, blood pressure, and endothelial ultrastructure.
AB  - The purpose of this study was to determine whether the renin-angiotensin system
      (RAS), nitric oxide (NO), atrial natriuretic peptide (ANP), blood pressure (BP),
      ultrastructural characteristics, and endothelium-dependent relaxation of thoracic
      aorta were modulated by the estrogen level. Rats were divided into 3 groups:
      ovariectomized (OVX); not ovariectomized (sham); and ovariectomized and treated
      with subcutaneous 17beta-estradiol (15 microg/kg/day, OVX+E(2)) (n=15-17 per
      group). For 13 weeks after surgery, blood pressure, serum estrogen, NO, plasma
      angiotensin II (Ang II), ANP, and renin activity levels were monitored. Thirteen
      weeks after surgery, the vasodilator responses of the aortic rings to
      acetylcholine and the ultrastructural characteristics of the thoracic aorta were
      determined. In the 9th and 13th week, OVX rats had a significantly higher blood
      pressure than the other two groups (p<0.05). Ovariectomy led to a significant
      decrease in plasma Ang II level and a significant increase in renin activity in
      OVX rats compared to sham rats; this effect could be reversed by estrogen
      treatment. In the 5th, 9th, and 13th weeks, the serum NO level was significantly
      lower in the OVX group than in the sham group (p<0.05); this effect could be
      reversed by estrogen treatment. Plasma ANP levels in the 9th and 13th weeks were
      significantly lower in the OVX group (p<0.05), and plasma ANP levels could be
      completely restored by estrogen treatment. Ovariectomy markedly reduced
      endothelium-dependent relaxation in response to acetylcholine in isolated rat
      thoracic aortic rings; chronic estrogen treatment significantly restored
      endothelium-dependent relaxation in response to acetylcholine. Under electron
      microscopy, the endothelial cells in OVX rats were swollen, even necrosed;
      estrogen treatment inhibited these changes. These results strongly suggest that
      estradiol protects rats from the development of hypertension and has a protective
      effect on the endothelium by increasing NO and ANP levels while decreasing renin
      activity. However, there was a discordance between the effects that estradiol had
      on angiotensin II and on blood pressure. This might be the result of negative
      feedback that ultimately results in the overall suppression of the RAS.

PMID- 18083252
TI  - Effect of angiotensin-converting enzyme inhibitor on serum asymmetric
      dimethylarginine and coronary circulation in patients with type 2 diabetes
      mellitus.
AB  - Measurements of serum asymmetric dimethylarginine (ADMA), an endogenous nitric
      oxide synthase inhibitor, and coronary flow velocity reserve (CFVR) using
      transthoracic Doppler echocardiography were performed at baseline and after 4
      weeks of temocapril therapy (2 mg/day) in 18 patients with type 2 diabetes.
      Although blood pressure, fasting blood sugar and lipid profiles remained
      unchanged, serum ADMA concentrations decreased significantly (0.51+/-0.08 to
      0.46+/-0.07 micromol/l, p<0.01) and CFVR increased significantly (2.78+/-0.36 to
      3.35+/-0.46, p<0.001) after the treatment. Moreover, a strong correlation was
      observed between the difference of ADMA and that of CFVR (r=-0.80, p<0.001).
      Temocapril reduced serum ADMA concentrations, improved CFVR beyond its blood
      pressure lowering effect. Our results suggest that decrease in ADMA by temocapril
      treatment is related to improvement of coronary circulation as determined by CFVR
      in patients with type 2 diabetes.

PMID- 18083253
TI  - Long-term outcomes of percutaneous coronary intervention for unprotected left
      main coronary artery disease.
AB  - BACKGROUND: This study evaluates the in-hospital, 30 day and long-term results of
      stenting for unprotected left main coronary artery disease in our institution.
      METHODS: Between April 2001 and October 2005 all unprotected left main cases were
      retrospectively reviewed. Outcomes were obtained by case note review and postal
      questionnaire; primary care physicians were contacted to complete missing data.
      RESULTS: We identified 100 consecutive patients who underwent unprotected left
      main procedures, 1.44% of the institution PCI volume. Indications for a
      percutaneous strategy were non-surgical candidates (47), emergency
      revascularisation (25) and patient/physician preference (28). Overall procedural
      success was 97%. The majority of cases (n=78) were performed with a single-stent
      strategy. 55% received a drug-eluting stent. There were 7 in-hospital deaths, 5
      in the emergency group (cardiogenic shock) and 2 non-CABG candidates. Post
      hospital discharge long-term clinical follow-up was 651+/-431 days (range 6
      1741). There were 8 deaths post discharge. Patients presenting as an emergency
      had a 72% survival rate at long-term follow-up, non-surgical candidates 83%, and
      patient/physician preference group had a 100% long-term survival. Multivariate
      analysis revealed cardiogenic shock (HR=7.9, 95% CI 1.7-3.6, p=0.008), failed
      thrombolysis (HR=8.5, 95% CI 1.7-41.7, p=0.008) and use of a bare-metal stent
      (HR=4.4, 1.1-17.0, p=0.034) were independent predictors of mortality.
      CONCLUSIONS: Our data suggest that in contemporary practice stenting for
      unprotected left main disease can be considered as an alternative treatment to
      surgery for selected patients. The results of randomised controlled trials are
      awaited.

PMID- 18083254
TI  - Should patients undergoing PCI still be consented for emergency bypass?
AB  - Informed consent for emergency coronary artery bypass grafting (CABG) is
      routinely obtained from patients undergoing percutaneous coronary intervention
      (PCI) and diagnostic angiography. Given the recent technological and
      pharmacological advances as well as increasing operator experience, we sought to
      assess the contemporary incidence of emergency CABG following PCI in our centre.
      In a total of 7855 consecutive PCIs, the overall rate of emergency CABG was
      0.11%, and the mortality risk was 0.67%. We believe that in the vast majority of
      patients undergoing PCI and diagnostic angiography, routine consent for emergency
      CABG is no longer appropriate.

PMID- 18083258
TI  - Finding solutions for the endless wait--reducing waiting times for radiotherapy.

PMID- 18083259
TI  - A (short) history of image-guided radiotherapy.
AB  - Progress in radiotherapy is guided by the need to realize improved dose
      distributions, i.e. the ability to reduce the treatment volume toward the target
      volume and still ensuring coverage of that target volume in all dimensions. Poor
      ability to control the tumour's location limits the accuracy with which radiation
      can be delivered to tumour-bearing tissue. Image-guided radiation therapy (IGRT)
      aims at in-room imaging guiding the radiation delivery based on instant knowledge
      of the target location and changes in tumour volume during treatment.
      Advancements are usually not to be attributed to a single event, but rather a
      combination of many small improvements that together enable a superior result.
      Image-guidance is an important link in the treatment chain and as such a major
      factor in this synergetic process. A historic review shows that many of the so
      called new developments are not so new at all, but did not make it into
      mainstream radiotherapy practice at that time. Recent developments in improved IT
      infrastructures, novel irradiation techniques, and better knowledge of functional
      and morphologic information may have created the need and optimal environment to
      revive the interest in IGRT.

PMID- 18083260
TI  - Class solution in inverse planned HDR prostate brachytherapy for dose escalation
      of DIL defined by combined MRI/MRSI.
AB  - PURPOSE: To establish an inverse planning set of parameters (class solution) to
      boost dominant intra-prostatic lesion (DIL) defined by MRI/MRSI. METHODS: For 15
      patients, DIL were contoured on CT or MR images and a class solution was
      developed to boost the DIL under the dosimetric requirements of the RTOG-0321
      protocol. To determine the maximum attainable level of boost for each patient, 5
      different levels were considered, at least 110%, 120%, 130%, 140% and 150% of the
      prescribed dose. The maximum attainable level was compared to the plan without
      boost using cumulative dose volume histogram (DVH). RESULTS: DIL dose escalation
      was feasible for 11/15 patients under the requirements. The planning target
      volume (PTV) dose was slightly increased, while the DIL dose was significantly
      increased without any violation of requirements. With slight adjustments of the
      dose constraint parameters, the dose escalation was feasible for 13/15 patients
      under requirements. CONCLUSION: Using a class solution, a dose escalation of the
      MRI/MRSI defined DIL up to 150% while complying with RTOG dosimetric requirements
      is feasible. This HDR brachytherapy approach to dose escalation allows a
      significant dose increase to the tumor while maintaining an acceptable risk of
      complications.

PMID- 18083261
TI  - Effect of relative inoculum concentration on Listeria monocytogenes growth in co
      culture.
AB  - Growth suppression of multi-species bacterial populations in batch cultures by a
      single 'dominant' strain has been referred to in the literature as the 'Jameson
      Effect'. The effect is often attributed to production of specific inhibitors of
      growth by one species against another. To explore its basis, we hypothesised that
      the Jameson Effect is often a non-specific interaction and that growth inhibition
      of species in co-culture can be controlled by manipulation of inoculum
      concentration and growth rate so as to enable a selected species to achieve
      stationary phase first. The hypothesis was assessed by co-culturing pairs of
      bacterial species under conditions selected to ensure that both strains grew at a
      similar rate and manipulating the initial concentration of each species.
      Specifically, the effect of inoculum concentration on the growth kinetics of
      Listeria monocytogenes when co-cultured in complex laboratory media with
      Escherichia coli, Pseudomonas fluorescens or a commercial strain of the lactic
      acid bacterium, Lactobacillus plantarum, was studied. Starting numbers of the
      second strain were either higher than ( approximately 10(6) cfu mL(-1)), equal to
      ( approximately 10(4) cfu mL(-1)) or lower than ( approximately 10(3) cfu mL(-1))
      L. monocytogenes. In most trials, the initial inoculum concentration governed
      which species became dominant and suppressed the growth of the other strain. L.
      monocytogenes was suppressed by all other strains when its inoculum level was
      lower. Conversely, when L. monocytogenes was initially present at higher
      concentration than either P. fluorescens or L. plantarum, their growth was
      suppressed. E. coli, however, was not suppressed by L. monocytogenes even when
      the E. coli density was initially lower. While simple competition for nutrients
      could explain most of the observations, in some co-culture experiments pH
      reduction also seemed to play a role in inhibition of growth of some species. In
      other cases, available growth substrates were apparently not utilised by both co
      cultured species, and the Jameson Effect did not occur. Thus, while it appears
      that under many conditions the Jameson Effect may be largely due to non-specific
      inhibition, more complex interactions between co-cultured strains involving
      species-specific pH limits for growth and differential utilisation of growth
      substrates may also occur and confound the simple Jameson Effect.

PMID- 18083262
TI  - Mycoflora and ochratoxin A producing strains of Aspergillus in Algerian wheat.
AB  - Wheat is a basic staple food for very large segments of the population of
      Algeria. The aim of this study is to analyse ochratoxin A (OTA)-producing mould
      and OTA-contaminated wheat. To evaluate the mycoflora and the potential for OTA
      production by Aspergillus strains, a total of 85 samples of wheat destined for
      human consumption were collected from two regions in Algeria (Tizi Ouzou and
      Setif) during the following phases: preharvest, storage in silos, and after
      processing. The mean value counts of fungi ranged from 275 to 1277 CFU g(-1). The
      dominant genus was Aspergillus, predominantly A. flavus, A. niger and A.
      versicolor. The other isolated species were A. ochraceus, A. alliaceus, A.
      carbonarius, A. terreus, A. fumigatus, A. candidus and Aspergillus spp. The
      occurrence and the levels of the genus Penicillium, Fusarium, Alternaria and
      Mucor were substantially lower than those of Aspergillus. The storage in silos
      shows high levels of Aspergillus (66 to 84%), especially A. flavus, but A. niger
      and other fungi were isolated at relatively low percentages. Equal distribution
      of the fungal contamination into the bran, flour and semolina fractions was
      observed from Flour Mill and Semolina Mill. The genus Aspergillus remained
      present at high levels at several phases of the production process. In addition,
      the ability to produce OTA by 135 isolates belonging to eleven species of
      Aspergillus and 23 isolates of Penicillium spp. was analyzed using fluorescent
      detection-based HPLC. Thus, it was found that 51 isolates (32.3%) were
      ochratoxigenic. All isolated strains of A. ochraceus (12) and A. alliaceus (6)
      produced OTA at concentrations ranging from 0.23 to 11.50 microg g(-1). Most of
      the A. carbonarius strains (80%) were OTA producers (0.01 to 9.35 microg g(-1)),
      whereas A. terreus (50%), A. niger (28%), A. fumigatus (40%), A. versicolor (18%)
      and Penicillium spp. (21.7%) were low level producers (0.01 to 0.07 microg g(
      1)). The concentration of OTA was determined in 30 samples of wheat. OTA was
      detected in 12 (40%) of the samples at levels ranging from 0.21 to 41.55 microg
      kg(-1).

PMID- 18083263
TI  - Characterization of pyranose dehydrogenase from Agaricus meleagris and its
      application in the C-2 specific conversion of D-galactose.
AB  - Pyranose dehydrogenase (PDH) of the mushroom Agaricus meleagris was purified from
      mycelial culture media to substantial homogeneity using ion-exchange and
      hydrophobic interaction chromatography. The native enzyme is a monomeric
      polypeptide with a molecular mass of 66,547Da as determined by matrix-assisted
      laser desorption/ionisation mass spectrometry containing approximately 7%
      carbohydrate and covalently bound flavin adenine dinucleotide. The enzyme
      exhibited a broad sugar substrate tolerance, oxidizing different aldopyranoses to
      the corresponding C-2 or C-2,3 (di)dehydro sugars. Preferred electron donors with
      the highest k(cat)/K(m) values were major sugar constituents of cellulose and
      hemicellulose, namely d-glucose, D-galactose, l-arabinose, D-xylose and
      cellobiose. This indicates a possible physiological role of the enzyme in
      lignocellulose breakdown. PDH showed no detectable activity with oxygen, and its
      reactivity towards electron acceptors was limited to various substituted
      benzoquinones and complexed metal ions, with the ferricenium ion and the
      benzoquinone imine 2,6-dichloroindophenole displaying the highest k(cat)/K(m).
      The enzyme catalyzed in up to 95% yields the regiospecific conversion of D
      galactose to 2-dehydro-D-galactose, an intermediate in a possible
      biotechnologically interesting process for redox isomerization of D-galactose to
      the prebiotic sugar D-tagatose.

PMID- 18083265
TI  - Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L
      lactide-co-glycolide) and its derivatives.
AB  - Biodegradable nano/microparticles of poly(D,L-lactide-co-glycolide) (PLGA) and
      PLGA-based polymers are widely explored as carriers for controlled delivery of
      macromolecular therapeutics such as proteins, peptides, vaccines, genes,
      antigens, growth factors, etc. These devices are mainly produced by emulsion or
      double-emulsion technique followed by solvent evaporation or spray drying. Drug
      encapsulation, particle size, additives added during formulation, molecular
      weight, ratio of lactide to glycolide moieties in PLGA and surface morphology
      could influence the release characteristics. Encapsulation efficiency and release
      rates through nano/microparticle-mediated drug delivery devices can be optimized
      to improve their therapeutic efficacy. In this review, important findings of the
      past decade on the encapsulation and release profiles of macromolecular
      therapeutics from PLGA and PLGA-based nano/microparticles are discussed
      critically in relation to nature and type of bioactive molecule, carrier polymer
      and experimental variables that influence the delivery of macromolecular
      therapeutics. Even though extensive research on biodegradable microparticles
      containing macromolecular drugs has greatly advanced to the level of production
      know-how, the effects of critical parameters influencing drug encapsulation are
      not sufficiently investigated for nano-scaled carriers. The present review
      attempts to address some important data on nano/microparticle-based delivery
      systems of PLGA and PLGA-derived polymers with reference to macromolecular drugs.

PMID- 18083264
TI  - Efficient gene silencing in metastatic tumor by siRNA formulated in surface
      modified nanoparticles.
AB  - We have developed a nanoparticle (NP) formulation for systemically delivering
      siRNA into metastatic tumors. The NP, composed of nucleic acids, a polycationic
      peptide and cationic liposome, was prepared in a self-assembling process. The NP
      was then modified by PEG-lipid containing a targeting ligand, anisamide, and thus
      was decorated for targeting sigma receptor expressing B16F10 tumor. The activity
      of the targeted NP was compared with the naked NP (no PEGylation) and non
      targeted NP (no ligand). The delivery efficiency of the targeted NP was 4-fold
      higher than the non-targeted NP and could be competed by excess free ligand.
      Luciferase siRNA was used to evaluate the gene silencing activity in the B16F10
      cells, which were stably transduced with a luciferase gene. The gene silencing
      activity of the targeted NP was significantly higher than the other formulations
      and lasted for 4 days. While confocal microscopy showed that the naked NP
      provided no tissue selectivity and non-targeted NP was ineffective for tumor
      uptake, the targeted NP effectively penetrated the lung metastasis, but not the
      liver. It resulted in 70-80% gene silencing in the metastasis model after a
      single i.v. injection (150 microg siRNA/kg). This effective formulation also
      showed very little immunotoxicity.

PMID- 18083266
TI  - Temporal treatment with interferon-beta prevents hepatocellular carcinoma in
      hepatitis B virus X gene transgenic mice.
AB  - BACKGROUND/AIMS: The preventive effect of interferon (IFN) against hepatocellular
      carcinoma (HCC) has been confirmed clinically. We sought to determine whether the
      temporal administration of IFN-beta prevents hepatocarcinogenesis in a mouse
      model where HCC develops without necroinflammation. METHODS: Hepatocarcinogenic
      mice that are transgenic for the hepatitis B virus X gene (HBx-Tg) were treated
      with IFN-beta or saline (control) for three months, from 3 to 6 months of age,
      and the incidence of HCC was determined at 18 months of age. The effects of IFN
      beta on DNA synthesis and apoptosis were tested. RESULTS: The incidence of HCC
      was significantly lower in the IFN-beta-treated mice than the controls (0 vs.
      50%, P<0.01). Inhibition of DNA synthesis in hepatocytes by IFN-beta was observed
      in the livers of HBx-Tg, without any significant induction of apoptosis. Although
      the treatment of IFN-beta was temporal, the number of hepatocytes with DNA
      synthesis remained lower 3 and 12 months later in life. CONCLUSIONS: Temporal
      administration of IFN-beta has a significant preventive effect on the occurrence
      of HCC in a mouse model where HCC develops without inflammation. The mechanisms
      are the inhibition of DNA synthesis and cell cycle progression of hepatocytes.

PMID- 18083268
TI  - When costs count: the impact of staff size, skill mix and treatment intensity on
      patient outcome for psychotherapeutic day treatment programmes.
AB  - The objective was to explore the relationship between staff related variables and
      patient outcome in day treatment programmes for patients with personality
      disorders. The importance of staff size, skill mix and treatment intensity (hours
      of treatment per week) was examined, in addition to location-specific effects.
      Multi-centre data routinely collected under non-experimental conditions from nine
      units, all members of a cooperative network in Norway, were analysed using a
      multilevel analysis. The data set consisted of treatment unit characteristics for
      the period 1993-2005, constituting an unbalanced panel of 71 units, together with
      information from 1574 patients who completed day treatment according to the plan.
      Patient outcome was measured by change in Global Assessment of Functioning Scale
      (GAF). Twelve per cent of variation in patient outcome was attributed to the
      treatment unit level. Staff size and treatment intensity influenced outcome to a
      minor extent, while an increased proportion of nurses or other college-educated
      personnel was associated with improved patient outcome. A positive location
      specific effect was found in one unit attached to a university. Potential cost
      savings seem to be apparent with respect to staff size and, to some extent, skill
      mix.

PMID- 18083267
TI  - Transferrin receptor 2 mediates uptake of transferrin-bound and non-transferrin
      bound iron.
AB  - BACKGROUND/AIMS: Transferrin receptor 2 appears to have dual roles in iron
      metabolism; one is signalling, the other is iron transport. It is sensitive to
      high levels of diferric transferrin, which is associated with disorders of iron
      overload. Also present in these disorders are increased levels of plasma non
      transferrin-bound iron. This study sought to clarify the role of transferrin
      receptor 2 in the uptake of transferrin-bound and non-transferrin-bound iron.
      METHODS: Variant Chinese Hamster Ovary (CHO) cells, transfected with transferrin
      receptor 2, were incubated with radio-labelled transferrin-bound or non
      transferrin-bound iron. Competition studies were performed in the presence of
      unlabelled dimetallic transferrin; knockdown was performed using specific siRNA.
      RESULTS: Cells expressing transferrin receptor 2 bound and internalised
      transferrin and transferrin-bound iron. Transferrin recycling occurred with an
      average cycling time of 11-15 min. Interestingly, the presence of transferrin
      receptor 2 was also associated with uptake of non-transferrin-bound iron which
      was inhibited by unlabelled transferrin-bound metals. Knockdown reduced
      transferrin-bound and non-transferrin-bound iron uptake by approximately 60%.
      CONCLUSIONS: Transferrin receptor 2 mediates transferrin-bound iron uptake by
      receptor-mediated endocytosis. It is also involved in the uptake of non
      transferrin-bound iron and the inhibition of non-transferrin-bound iron uptake by
      diferric transferrin in CHO cells.

PMID- 18083269
TI  - A hybrid method for parameter estimation and its application to biomedical
      systems.
AB  - A general version of a hybrid method for parameter estimation is presented with a
      theoretical support and an illustrative example of application. This method
      consists of a curve fitting algorithm that takes the initial estimate of the
      parameterization from an artificial neural network. The idea is to improve the
      convergence of the algorithm to the sought parameterization using a close initial
      estimate. The motivation arises from biomedical problems where one is interested
      in obtaining a meaningful estimate so that it can be used for both description
      and prediction purposes. Two strategies are proposed for the application of the
      hybrid method: one is of general applicability, the other is intended for systems
      defined by the series connection of various blocks. The feasibility of the method
      is illustrated with a case study related to the neuromuscular blockade of
      patients undergoing general anaesthesia.

PMID- 18083270
TI  - Tumor volume and tumor marker index based on CYFRA 21-1 and CEA are strong
      prognostic factors in operated early stage NSCLC.
AB  - The aim of the study was to analyze the relation between tumor volume (V(path)),
      tumor marker index (TMI) and prognosis in 261 completely resected (R0) stages I
      and II non-small cell lung cancer (NSCLC) patients by univariate and multivariate
      analyses. V(path) was calculated as an ellipsoid body. TMI represents the
      geometric mean of normalized CYFRA 21-1 and CEA values. Patients with a V(path)<
      or =13.7cm(3) had a significantly better 5-year-survival rate than patients with
      a V(path)>13.7cm(3) (78.1% vs. 47.9%; p<0.001). Patients with a TMI< or=0.54 had
      a 5-year-survival rate of 79.1% compared to only 47.2% in patients with a
      TMI>0.54 (p<0.001). Besides age (>70 years), performance status and gender, both
      V(path) (>13.7 cm(3)) and TMI (>0.54) bore significance in the multivariate Cox
      model with a hazard ratio (HR) of 1.9 (95% CI: 1.1-3.3, p=0.016) and 2.3 (95% CI:
      1.3-4.2, p=0.006), respectively. Based on a combination of V(path) and TMI, a low
      risk group (17% of the patients) with both parameters in the normal range could
      be identified. Patients with elevated V(path) or TMI (31%) had an intermediate HR
      of 3.4 (95% CI: 1.3-9.2). When both factors were elevated (52% of patients) the
      HR increased to 5.95 (95% CI: 2.4-14.9). The elevation of V(path) and TMI was
      found in 46.2% of stage I and in 59.1% of stage II. The 5-year-survival rates
      were found to be 89.1, 62.2 and 43.0%, respectively. In conclusion, elevated
      levels of TMI and V(path) have a strong negative prognostic impact on survival in
      operated early stage of NSCLC. These patients might be considered for adjuvant
      chemotherapy.

PMID- 18083271
TI  - Mixing-controlled biodegradation in a toluene plume--results from two-dimensional
      laboratory experiments.
AB  - Various abiotic and biotic processes such as sorption, dilution, and degradation
      are known to affect the fate of organic contaminants, such as petroleum
      hydrocarbons in saturated porous media. Reactive transport modeling of such
      plumes indicates that the biodegradation of organic pollutants is, in many cases,
      controlled by mixing and therefore occurs locally at the plume's fringes, where
      electron donors and electron-acceptors mix. Herein, we aim to test whether this
      hypothesis can be verified by experimental results obtained from aerobic and
      anaerobic degradation experiments in two-dimensional sediment microcosms. Toluene
      was selected as a model compound for oxidizable contaminants. The two-dimensional
      microcosm was filled with quartz sand and operated under controlled flow
      conditions simulating a contaminant plume in otherwise uncontaminated
      groundwater. Aerobic degradation of toluene by Pseudomonas putida mt-2 reduced a
      continuous 8.7 mg L(-1) toluene concentration by 35% over a transport distance of
      78 cm in 15.5 h. In comparison, under similar conditions Aromatoleum aromaticum
      strain EbN1 degraded 98% of the toluene infiltrated using nitrate (68.5+/-6.2 mg
      L(-1)) as electron acceptor. A major part of the biodegradation activity was
      located at the plume fringes and the slope of the electron-acceptor gradient was
      steeper during periods of active biodegradation. The distribution of toluene and
      the significant overlap of nitrate at the plume's fringe indicate that biokinetic
      and/or microscale transport processes may constitute additional limiting factors.
      Experimental data is corroborated with results from a reactive transport model
      using double Monod kinetics. The outcome of the study shows that in order to
      simulate degradation in contaminant plumes, detailed data sets are required to
      test the applicability of models. These will have to deal with the incorporation
      of existing parameters coding for substrate conversion kinetics and microbial
      growth.

PMID- 18083272
TI  - Baseline nail disease in patients with moderate to severe psoriasis and response
      to treatment with infliximab during 1 year.
AB  - BACKGROUND: Although nail psoriasis occurs frequently in patients with psoriatic
      skin lesions, effective treatments are limited. OBJECTIVE: Occurrence of nail
      psoriasis by type and incidence of nail clearance using the Nail Psoriasis
      Severity Index were evaluated. METHODS: This was a 50-week, phase III study in
      which 378 patients with moderate to severe psoriasis were randomized 4:1 to
      infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and every 8 weeks through week
      46, with placebo crossover to infliximab at week 24. RESULTS: Of the 373
      evaluated patients, 305 (81.8%) had baseline nail psoriasis. The right thumbnail
      was most often the worst involved nail, and pitting and onycholysis were the most
      common lesions. Among patients with baseline nail psoriasis, 6.9%, 26.2%, and
      44.7% in the infliximab group had nail disease clearance at weeks 10, 24, and 50,
      respectively, versus 5.1% in the placebo group at week 24 (P < .001). Mean
      percent improvements in Nail Psoriasis Severity Index score at weeks 10 and 24
      were 26.8% and 57.2%, respectively, in the infliximab group versus -7.7% and 
      4.1%, respectively, in the placebo group (both P < .001). At week 24, mean
      percent improvements in nail matrix and nail bed features were 52.9% and 69.2%,
      respectively (vs -1.9% and 18.4% for placebo; P < .001). LIMITATIONS: The study
      did not evaluate nail response beyond 1 year. CONCLUSIONS: Patients with
      psoriasis receiving infliximab experienced marked and sustained nail improvement.

PMID- 18083273
TI  - Comparison of histopathologic-clinical characteristics of Jessner's lymphocytic
      infiltration of the skin and lupus erythematosus tumidus: Multicenter study of 46
      cases.
AB  - OBJECTIVE: We sought to identify criteria able to distinguish between Jessner's
      lymphocytic infiltration of the skin (JLIS) and lupus erythematosus tumidus
      (LET). METHODS: The following characteristics were recorded in a retrospective,
      multicenter analysis of patients with JLIS and LET: clinical features (number,
      size, type, and localization of lesions; photosensitivity; extracutaneous signs),
      histologic findings, phototesting, lupus serology, treatment, and outcome.
      Available histologic slides were reviewed blinded to the initial diagnosis using
      a pre-established grid. RESULTS: Univariate analysis of data from patients with
      JLIS (15 women, 17 men; mean age: 35 years) and LET (13 women, one man; mean age:
      31 years) showed the following significant (P < .05) differences: more frequent
      back involvement and annular lesions in JLIS, as opposed to female predominance,
      more frequent face involvement, and plaques in LET. Phototesting, especially
      ultraviolet B, induced lesions in 18 of 26 patients with JLIS and all 4 with LET.
      The blinded histologic review (33 samples) only found slight epidermal atrophy
      and focal thickened dermoepidermal junction more frequent and perivascular
      lymphocyte infiltrations less dense in LET. The two groups of patients
      reclassified according histopathologic features (18 LET and 11 JLIS) showed only
      slight clinical differences (more frequent nasal bridge lesions in LET and
      annular lesions in JLIS). LIMITATION: The retrospective nature of the study is a
      limitation. CONCLUSION: JLIS and LET in this population showed more similarities
      than differences, supporting a continuous spectrum covering these two entities.

PMID- 18083274
TI  - The effect of weight on the efficacy of biologic therapy in patients with
      psoriasis.
AB  - BACKGROUND: The prevalence of obesity is rapidly increasing in the United States.
      Patients with psoriasis, in particular, tend to be above normal weight. Three of
      the 5 biologics used to treat psoriasis are fixed-dosed treatments: alefacept,
      etanercept, and adalimumab. Dosing regimens do not account for weight. OBJECTIVE:
      We attempted to determine whether the efficacy of the biologics is affected by
      weight. METHODS: We review the existing body of literature, including subgroup
      analyses, relating to efficacy and weight for infliximab, efalizumab, alefacept,
      and etanercept. No relevant literature was found for adalimumab. RESULTS: Weight
      based dosed medications do not seem to lose efficacy with increasing weight. Both
      etanercept and alefacept may have compromised efficacy in heavier individuals.
      LIMITATIONS: The data are limited to subgroup analyses and smaller studies, often
      with no statistical significance reported. CONCLUSIONS: Additional studies are
      warranted, specifically designed to address the issue of obesity and response to
      therapy of the biologics. Alternative dosing for etanercept and alefacept should
      be further evaluated in patients above normal weight.

PMID- 18083276
TI  - No cross-sectional influence of APOE epsilon4 dose on clinical tests in
      Alzheimer's disease.
AB  - This study sought to determine if there are detectible influences on the symptoms
      of Alzheimer's disease (AD) from the genetic risk factor for AD, the epsilon4
      allele of apolipoprotein-E (APOE). Using data from two cohorts of AD patients, a
      cross-sectional latent variable model of AD was tested with three symptom factors
      explaining variability in the observed variables after taking a general
      neurological factor into account. No significant influence of epsilon4 was
      detected. APOE's effect in AD may occur prior to clinical symptoms, or may simply
      be more subtle than these instruments can detect.

PMID- 18083275
TI  - Effect of cholesterol on the interaction of the amphibian antimicrobial peptide
      DD K with liposomes.
AB  - DD K is an antimicrobial peptide previously isolated from the skin of the
      amphibian Phyllomedusa distincta. The effect of cholesterol on synthetic DD K
      binding to egg lecithin liposomes was investigated by intrinsic fluorescence of
      tryptophan residue, measurements of kinetics of 5(6)-carboxyfluorescein (CF)
      leakage, dynamic light scattering and isothermal titration microcalorimetry. An 8
      nm blue shift of tryptophan maximum emission fluorescence was observed when DD K
      was in the presence of lecithin liposomes compared to the value observed for
      liposomes containing 43 mol% cholesterol. The rate and the extent of CF release
      were also significantly reduced by the presence of cholesterol. Dynamic light
      scattering showed that lecithin liposome size increase from 115 to 140 nm when
      titrated with DD K but addition of cholesterol reduces the liposome size
      increments. Isothermal titration microcalorimetry studies showed that DD K
      binding both to liposomes containing cholesterol as to liposomes devoid of it is
      more entropically than enthalpically favored. Nevertheless, the peptide
      concentration necessary to furnish an adjustable titration curve is much higher
      for liposomes containing cholesterol at 43 mol% (2 mmol L(-1)) than in its
      absence (93 micromol L(-1)). Apparent binding constant values were 2160 and
      10,000 L mol(-1), respectively. The whole data indicate that DD K binding to
      phosphatidylcholine liposomes is significantly affected by cholesterol, which
      contributes to explain the low hemolytic activity of the peptide.

PMID- 18083277
TI  - Oral vaccination of dogs (Canis familiaris) with baits containing the recombinant
      rabies-canine adenovirus type-2 vaccine confers long-lasting immunity against
      rabies.
AB  - Rabies is a reemerging and fatal infectious disease in Asia mainly caused by
      exposure to rabid dogs. Prevention of dog rabies would be the most effective way
      to stop rabies transmission to humans. However, vaccinating stray dogs in urban
      and rural areas using conventional vaccines is always difficult and is not cost
      effective for use in most areas including China. Further to previous studies from
      our laboratory, we developed a bait containing the recombinant rabies vaccine and
      performed a non-parenteral trial in dogs. This vaccine was intranasally
      administrated once to 46 dogs in solution form with 1 x 10(8.5) PFU and orally to
      90 dogs in specially designed baits with 3 x 10(8.5) PFU of the recombinant
      canine adenovirus. Results showed that about 87.5% (119/136) of the immunized
      dogs developed virus neutralizing antibodies (VNA). The immune response against
      rabies in dogs was detectable at 2-3 weeks after administration, reaching a peak
      by 5-6 weeks. Among the seroconverted animals, 90.8% (108/119) elicited a VNA
      response for over 24 months. The antibody titer during the 2 years was above
      0.5IU /ml while showing a gradual but slow decline from the 6th week after
      vaccination. In a challenge experiment of 10 dogs with 60,000 mouse LD(50) of CVS
      24 2 years after the vaccination, all the dogs survived. This demonstrated that
      the recombinant vaccine could be orally administrated and the bait was effective
      for the oral vaccination of dogs.

PMID- 18083278
TI  - Traditional smallpox vaccination with reduced risk of inadvertent contact spread
      by administration of povidone iodine ointment.
AB  - One concern with traditional smallpox vaccination is inadvertent spread of virus
      to atopic or immunocompromised contacts. To reduce this risk, we tested the
      ability of povidone iodine to inactivate infectious virus at the vaccination site
      beginning at 7 days after transcutaneous smallpox vaccination. This ointment
      rapidly inactivated virus on the skin without reducing neutralizing antibody
      titers or antiviral T cell responses. Moreover, there was no delay in
      healing/eschar separation following povidone iodine application. Together, this
      indicates that administration of an antiviral/antimicrobial cream can effectively
      block virus shedding after traditional smallpox vaccination and reduce the risks
      of autoinoculation or contact spread.

PMID- 18083279
TI  - pcDNA-IL-12 vaccination blocks eosinophilic inflammation but not airway
      hyperresponsiveness following murine Toxocara canis infection.
AB  - We have investigated the effect of pcDNA3-CpG and pcDNA-IL-12, delivered by
      intradermal gene gun administration, on the blood/lung eosinophilia, airway
      hyperresponsiveness as well as the immune response in a murine model of
      toxocariasis. Our results demonstrated that pcDNA-IL-12 but not pcDNA3-CpG
      vaccination led to a persistent lower blood/bronchoalveolar eosinophilia
      following Toxocara canis infection, as pcDNA3-CpG led only to an early transient
      blockage of eosinophil transmigration into bronchoalveolar fluid following T.
      canis infection. Prominent Type-1 immune response was pointed out as the hallmark
      of T. canis infection following pcDNA-IL-12 vaccination. Outstanding IFN-gamma/IL
      4 ratio besides low levels of IgG1 with subsequent high IgG2a/IgG1 ratio further
      characterized a Type-1 polarized immunological profile in pcDNA-IL-12-vaccinated
      animals. Nevertheless, only pcDNA3-CpG was able to prevent airway
      hyperresponsiveness induced by T. canis infection. The persistent airway
      hyperresponsiveness observed in pcDNA-IL-12-vaccinated animals demonstrated that
      the airway constriction involved other immunological mediator than those blocked
      by pcDNA-IL-12. Together, these data indicated that pcDNA-IL-12 and pcDNA3-CpG
      vaccines have distinct therapeutic benefits regarding the eosinophilic
      inflammation/airway hyperresponsiveness triggered by T. canis infection,
      suggesting their possible use in further combined therapeutic interventions.

PMID- 18083280
TI  - Accelerated apoptosis of blood leukocytes and oxidative stress in blood of
      patients with major depression.
AB  - Acceleration of blood leukocyte apoptosis in major depression has been described.
      The present studies have been undertaken to estimate the level of apoptosis of
      blood leukocytes in patients with depression and to examine the mechanisms
      leading to apoptosis. Blood was taken from 29 patients with depression (age
      48.2+/-11.2, 14 males, 15 females) and 30 healthy controls (age 41.3+/-4.1, 15
      males, 15 females), and apoptosis was estimated by the cytometric method by
      measurements of annexin V binding, mitochondrial membrane potential (DeltaPsi),
      bcl-2, bax, and Fas (CD95) expression in CD4+, CD8+ and CD14+ cells. The amounts
      of cytochrome c released from mitochondria to cytosol of peripheral blood
      mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) were also measured.
      The levels of reactive oxygen species (ROS) released from PMNs were examined as
      was the serum activity of superoxide dismutase (SOD), catalase (CAT), and total
      peroxidase (PER). Additionally, serum levels of the tumor necrosis factor (TNF
      alpha) and interleukin-6 (IL-6) were estimated. Our experiments indicated
      accelerated apoptosis of CD4+ T lymphocytes and CD14+ cells (mainly neutrophils)
      of depressed patients as well as a significant increase in the percent of Fas
      expressing cells. Bcl-2 and bax expression was higher in cells of depressed
      patients than in control, however, bcl-2/bax ratio was significantly decreased in
      CD14+ cells of depressed patients. PMNs isolated from the blood of the patients
      produced more ROS spontaneously and after induction with phorbol ester (PMA) than
      PMNs of the healthy control. A significant increase in serum activity of SOD, CAT
      and PER was also detected. Overproduction of superoxide anion correlated
      positively with the level of PMNs apoptosis (measured by cytochrome c release),
      suggesting that superoxide anion might be an important factor inducing apoptotic
      death of blood cells. The result of our experiment indicated that apoptosis of
      immune cells may affect patient's susceptibility to different infections and
      application of antioxidants in medication of patients with depression will be
      beneficial for them. The increased level of IL-6 in sera of the depressed
      patients did not correlate with overproduction of ROS, suggesting that this
      cytokine is not involved in oxidative stress and apoptosis of leukocytes.

PMID- 18083281
TI  - Potential effects of zinc on information processing in boys with attention
      deficit hyperactivity disorder.
AB  - PURPOSE: The aims of the present study were to investigate the relationship
      between plasma zinc levels and amplitudes and latencies of P1, N2, and P3 in
      parietal and frontal areas in children with ADHD, and to compare these zinc
      levels and event-related potentials (ERPs) indices with controls. METHODS: 28
      boys with ADHD were divided into two groups according to plasma zinc levels: low
      zinc group (N=13, zinc level <80 microg/dL) and zinc non-deficient group (N=15,
      zinc level >or=80 microg/dL). ERP indices from parietal and frontal brain regions
      were recorded in children with ADHD and in 24 normal boys by using an auditory
      oddball paradigm. Plasma zinc levels were measured by an atomic absorption
      spectrophotometer. RESULTS: The plasma zinc levels were significantly lower in
      both ADHD groups (means are 65.8 microg/dL in low zinc group and 89.5 microg/dL
      in zinc non-deficient group) than controls (mean: 107.8 microg/dL; both p values
      <0.017). In ADHD compared to controls, the amplitudes of P3 in frontal and
      parietal regions were significantly lower, and the latency of P3 in parietal
      region was significantly longer (all p values <0.017). In low zinc ADHD group
      compared to zinc non-deficient ADHD group, the latencies of N2 in frontal and
      parietal region were significantly shorter (all p values <0.017). In addition,
      there was a medium but significant positive correlation between plasma zinc
      levels and amplitude and latency of frontal N2 wave in ADHD. CONCLUSIONS: These
      results can suggest that plasma zinc levels might have an effect on information
      processing in ADHD children, and lower zinc levels seem to affect N2 wave. Since
      N2 wave changes may reflect a different inhibition process, further studies are
      warranted to investigate the effect of zinc on inhibitory process in children
      with ADHD, and in low zinc and non-deficient ADHD groups.

PMID- 18083282
TI  - PCB concentrations in some foods from four European countries.
AB  - Samples of salmon, butter and cabbage from Belgium, Italy, Spain and Portugal
      were analysed for their content in total, non-dioxin-like (as represented by the
      so-called seven indicator-PCBs: congeners 28, 52, 101, 118, 138, 153 and 180) and
      dioxin-like PCBs (mono-ortho and non-ortho PCBs). Salmon and cabbage from
      Belgium, and butter from Portugal and Belgium, contained less total and non
      dioxin-like PCBs than those from other countries. Samples from Italy had the
      highest concentrations. Similar patterns were observed for dioxin-like PCBs (as
      represented by the TCDD-equivalents of toxicity, WHO-TEQs), with the lowest
      values in Belgium and Portugal for salmon, in Portugal for butter and in Belgium
      for cabbage. Differences up to five-fold in PCB concentrations and TEQ values
      were seen among commodities from the four countries. The implication is that it
      might be worthwhile monitoring, with selection of the least contaminated
      commodities, to reduce the PCB exposure of the general population. This could
      have health consequences, because daily intakes are higher than the tolerable
      levels for a considerable part of the European population.

PMID- 18083283
TI  - The Nrf2-Keap1 defence pathway: role in protection against drug-induced toxicity.
AB  - The metabolic biotransformation of xenobiotics to chemically reactive metabolites
      can, in some instances, underlie the pathogenesis of certain adverse drug
      reactions, due to the development of chemical or oxidative stress. In order to
      guard against such stresses, mammalian cells have evolved multi-faceted, highly
      regulated defence systems, one of the most important being that which is
      regulated by the transcription factor Nrf2. Through regulating the expression of
      numerous cytoprotective genes, Nrf2 serves as a critical determinant of a cell's
      capacity to survive, or succumb, to a toxic insult. The aim of this review is to
      summarise our current understanding of the biochemistry that underlies the Nrf2
      defence pathway, and highlight the important role of this transcription factor in
      the protection against drug-induced toxicity, primarily through the examination
      of recent investigations that have demonstrated an increased vulnerability to
      various toxins in animals lacking Nrf2.

PMID- 18083284
TI  - CPR during ischemia and reperfusion: a model for survival benefits.
AB  - OBJECTIVE: Manual CPR improves the likelihood of neurologically intact survival
      following cardiac arrest. The mechanism of this benefit is not completely
      understood. We propose a mechanism whereby manual CPR simultaneously limits
      ischemia and specifically protects against reperfusion injury. We derive a
      conceptual framework that describes cell survival as it relates to the ischemic
      and reperfusion stages and CPR effects. RESULTS: Based on a synthesis of basic
      science and clinical information, we propose that the benefit of the subnormal
      circulation produced by manual CPR is multifaceted and specifically includes
      attenuating reperfusion injury by providing graded blood flow to the heart and
      brain. Although manual CPR produces reperfusion pathophysiology, the low flow
      from CPR limits reperfusion injury specifically through mechanisms of post
      ischemic conditioning which include attenuating peak levels of oxidative
      substrate and activating pathways that protect against oxidative stress.
      CONCLUSIONS: If such a hypothesis of post-ischemic conditioning is borne out, CPR
      may be considered a dose-sensitive therapy whereby certain physiologic states
      would be best served by different levels of circulation and hence distinct grades
      of CPR.

PMID- 18083285
TI  - Increased prevalence of sustained return of spontaneous circulation following
      transition to biphasic waveform defibrillation.
AB  - PRIMARY OBJECTIVE: We sought to assess the prevalence of shock-induced sustained
      return of spontaneous circulation (ROSC) and neurologically intact discharge
      survival before (1990-1997) and after (1998-2006) transition to biphasic waveform
      defibrillation in our population-controlled EMS setting. MATERIALS AND METHODS:
      All victims of out-of-hospital cardiac arrest with ventricular fibrillation as
      the initial rhythm from November 1990 to December 2006 were included for
      analysis. Data were acquired prospectively and analyzed retrospectively during
      two periods: before (period 1) and after (period 2) transition from monophasic
      damped sine to biphasic truncated exponential and rectilinear biphasic waveform
      defibrillation. We compared the prevalence of sustained ROSC and survival in the
      two periods. RESULTS: Very high survival was observed during both periods. During
      period 1, sustained ROSC with shocks only was obtained in 37 (27.6%) patients; in
      period 2, sustained ROSC was obtained in 39 (40.2%) (p=0.04). Fifty-three (39.6%)
      survived to neurologically intact discharge in period 1, and 45 (46.4%) in period
      2 (p=0.29). For bystander-witnessed arrests, ROSC was obtained in 34 (31.5%) in
      period 1 and 34 (45.3%) in period 2 (p=0.06). Forty-eight (44.4%) survived in
      period 1 and 39 (52.0%) in period 2 (p=0.31). We observed no other significant
      differences in patient or EMS-performance characteristics in the two time
      periods. CONCLUSIONS: Return of sustained pulses with shocks alone increased
      after transition to biphasic waveform defibrillation, with no other differences
      to explain the increase. High survival was noted in both periods, with a trend
      toward higher survival in the second period.

PMID- 18083287
TI  - Mobile phone CPR: the national campaign in South Korea.

PMID- 18083286
TI  - Determinants of the quality of basic life support by hospital nurses.
AB  - INTRODUCTION: Good quality basic life support (BLS) results in better survival.
      BLS is a core competence of nurses but despite regular refresher training, the
      quality of BLS is often poor and the reasons for this are not well known. We
      therefore investigated the relation between BLS quality and some of its potential
      determinants. MATERIALS AND METHODS: During a BLS refresher course, 296 nurses
      from non-critical care wards completed a questionnaire including demographic data
      and a "self-confidence" score. Subsequently, they performed a BLS test on a
      manikin connected to a PC using Skillreporting System software (Laerdal, Norway).
      The following variables were recorded: number of ventilations/min, tidal volume,
      number of compressions/min, compression rate, compression depth, "good
      ventilation" (n >or=4 min(-1) and tidal volume=700-1000 ml) and "good
      compression" (n >or=40 min(-1) and rate=80-120 min(-1) and compression depth=40
      50mm). To detect independent determinants of BLS quality, associations between
      the demographic data and the objective variables of BLS quality were examined.
      RESULTS: Forty-three percent of the nurses rated their confidence as good or very
      good. Male gender was associated with good compression (P<0.001). Greater self
      confidence was also associated with good ventilation (P<0.03) and with good
      compression (P<0.001). A short time since last BLS training was associated with a
      higher number of ventilations/min (P=0.01). A short time since last experience of
      CPR was associated with a higher number of compressions (P<0.01). CONCLUSIONS:
      Male gender, greater self-confidence, recent BLS training and recent CPR were
      associated with better quality of BLS.

PMID- 18083288
TI  - Quality of CPR during advanced resuscitation training.
AB  - INTRODUCTION: Previous studies have documented poor quality CPR during real life
      resuscitation attempts. This study investigated whether poor quality CPR during
      advanced life support training could be contributing to poor performance in
      clinical practice. METHODS: Observational study of quality of CPR during advanced
      life support training courses before and after the implementation of the European
      Resuscitation Council Guidelines 2005 into the ALS course. The quality of chest
      compressions were downloaded from a manikin and direct observations of no-flow
      time; pre-shock pauses were recorded. RESULTS: 94 cardiac arrest simulations were
      studied (46 before implementation of Guidelines 2005 and 48 after). Delays in
      starting CPR, inadequate compression depth, prolonged interruptions of chest
      compressions and excessive pre-shock pauses were identified. The introduction of
      Guidelines 2005 resulted in improvements in the number of compressions given per
      minute and a reduction in no-flow time and duration of pre-shock pauses, but
      overall the quality of CPR performed during the ALS course remained poor. There
      was little evidence of performance improving over successive simulations as the
      course progressed. CONCLUSION: The implementation of Guidelines 2005 into the ALS
      course appear to have improved the process of CPR by reducing no-flow time during
      simulated CPR. However, the quality of CPR during ALS training remains sub
      optimal. Delays in starting CPR, inadequate compression depth, excessive
      interruptions in chest compressions and prolonged pre-shock pauses mirror
      observations from clinical practice. Strategies to improve CPR performance during
      ALS training should be explored and potentially may result in improvements in
      clinical practice.

PMID- 18083289
TI  - Persistent neurochemical changes in neonatal piglets after hypoxia-ischemia and
      resuscitation with 100%, 21% or 18% oxygen.
AB  - BACKGROUND: Neonatal hypoxia-ischemia (HI) is a common complication of pregnancy
      and delivery. Conventional clinical practice is to resuscitate neonates with 100%
      O2, and evidence is building to suggest resuscitation with lower O2
      concentrations is safer. Significant neurochemical changes are associated with HI
      injury and persistent changes in amino acids are related to cell death, therefore
      we used a swine survival model of neonatal HI-reoxygenation (HI/R) to investigate
      the effects of resuscitation with 100%, 21% or 18% O2 on amino acid
      neurotransmitters. METHODS: In a blinded randomized fashion, following permanent
      ligation of the left common carotid artery, newborn pigs (1-4 d, 1.7-2.5 kg)
      received alveolar normocapnic hypoxia (FiO2=0.15, 2h) and were reoxygenated with
      18%, 21% or 100% O2. After a 4-day survival period, brain regions were processed
      for amino acid levels using high-performance liquid chromatography (HPLC).
      RESULTS: Results showed that resuscitation with different O2 concentrations
      caused hemispheric and regional changes in all amino acids investigated including
      glutamate, alanine, gamma-amino butyric acid, glycine and aspartate, 4 days post
      HI. Resuscitation with 100% O2 significantly increased glutamate and glycine in
      the dorsal cortex contralateral to the ligated common carotid artery, compared to
      piglets resuscitated with 21% O2. Additionally, piglets resuscitated with 21% O2
      had significantly lower alanine levels than those resuscitated with 18% O2.
      CONCLUSION: Significant resuscitation-dependent changes in amino acid
      neurotransmitters are still evident 4 days post-HI in the newborn piglet. These
      data suggest that persistent changes in neurochemistry occur 4 days after HI/R
      and further studies are warranted to elucidate the consequences of this on
      neonatal brain development.

PMID- 18083290
TI  - Location and features of instructive spatial cues do not influence the time
      course of covert shifts of visual spatial attention.
AB  - The time course of shifting visual spatial attention to flickering stimuli in the
      left and right visual hemifield was investigated. The goal was to test whether an
      instructive peripheral salient cue located close to the newly to-be-attended
      location triggers faster shifts per se compared to a central cue. Besides
      behavioural data an objective electrophysiological measure, the steady-state
      visual evoked potential (SSVEP) was used to measure the time course of visual
      pathway facilitation in the human brain for centrally and peripherally cued
      shifts of spatial attention. Results revealed that both spatial cues resulted in
      identical time courses of shifts of covert spatial attention. This was true with
      respect to behavioural data and SSVEP amplitude. Results support the notion that
      a salient peripheral spatial cue does not automatically produce faster shifts of
      spatial attention to the to-be-attended location when this cue is informative and
      embedded in an ongoing stimulation.

PMID- 18083291
TI  - Factors driving deforestation in common-pool resources in northern Mexico.
AB  - The theory of collective action has been extensively used to explain the
      relationship between common-based property regimes and the conservation of
      natural resources. However, there are two key components of the theory that
      literature reports as puzzles in which no consensus exists about their effect on
      the performance of common-pool resources. These are group size and heterogeneity.
      This study analyzes the effects of these two key components on the effectiveness
      of community-based forestry, called ejidos, to protect their forest resources in
      northern Mexico. We used a multinomial logit model to determine the contribution
      of 16 explanatory variables to the dependent variable, a measure of success of
      ejidos defined by the presence of deforested, degraded, or forested conditions.
      The results show that corn yield, marginality, percent of forest area, total
      population, a forest value index, distance to markets, roads and towns, were all
      statistically significant in driving deforested conditions. Deforestation becomes
      more attractive for poor communities and as corn yield and distance to towns,
      roads, and markets decrease. In general, group size and heterogeneity had no
      significant effects on the presence of deforested conditions. Deforestation is
      driven by resource-specific characteristics, such as location and soil
      productivity, not by ejidos' attributes, such as total area or number of members.
      We argue that current institutional policies focusing on the structure of
      property right arrangements should be shifted (1) to provide better technology
      for land cultivation; (2) to reduce the marginality problem in poor communities;
      and (3) to strengthen local institutions.

PMID- 18083292
TI  - Virgin and recycled engine oil differentiation: a spectroscopic study.
AB  - As a result of the changes that occur during their use, used engine oils tend to
      differ in chemical and physical composition from a virgin oil. In general
      recycled oils have: much higher water and sediment levels than virgin oil;
      relatively higher concentrations of organic compounds (oxidation products); and
      relatively higher levels of metals such as Fe, Cd, Cr, Pb, etc. Therefore, the
      aim of this work was to investigate, assess and to observe, by means of the
      physical and the chemical properties of the oils, atomic absorption (AA),
      inductive couple plasma (ICP) and Fourier transform infrared (FTIR) analyses the
      extent of the differences occurring between the virgin and recycled oil. In
      important part of this work was also the development of analytical techniques
      based on the use of FTIR spectroscopy; in relation to the rapid analysis of
      lubricants; in particular for the differentiation of virgin and recycled oil. The
      results obtained were expected to be useful for differentiation purposes,
      providing information on whether the metal concentrations and oxidation products
      could be an appropriate feature for differentiating a particular oil sample from
      the others. This work is categorized into a two-step procedure. Firstly, an
      evaluation of a typical FTIR spectrum of an engine oil sample (mono- and
      multigrade) is presented. The broad feature centered at 1716 cm(-1) is due to the
      presence of carbonyl containing degradation products of oil. A band observed at
      1732, 1169, 1154 and 1270 cm(-1) assigned to the polymethacrylate stretching
      vibrations, allows the determination of viscosity modifier and pour point
      depressant additives. The observed differences in the specific spectral bands
      (1732, 1169, 1154 and 1270 and 1716 cm(-1)) are investigated and discussed.
      Secondly, an analytical technique for the measurement of the levels of the wear
      metals is also applied.

PMID- 18083293
TI  - Stents and urethral strictures: a lesson learned?

PMID- 18083294
TI  - Validation of the contemporary epstein criteria for insignificant prostate cancer
      in European men.
AB  - OBJECTIVES: The Epstein criteria represent the most widely used scheme for
      prediction of clinically insignificant prostate cancer (PCa). However, they were
      never validated in European men. We assessed the rate of unfavorable prostate
      cancer (Gleason 7-10 or non-organ-confined disease) in a cohort of 366 men who
      fulfilled the Epstein clinically insignificant PCa criteria. METHODS: Between
      1996 and 2006, 2580 men underwent radical prostatectomy at a single academic
      European institution. Of those, 366 fulfilled the contemporary Epstein clinically
      insignificant PCa criteria. Analyses targeted the rate of pathologically
      unfavorable prostate cancer, defined as either Gleason sum 7-10 or non-organ
      confined disease, or a combination of these characteristics in patients with
      clinically insignificant PCa. RESULTS: Gleason 7-10 prostate cancer at radical
      prostatectomy was found in 88 patients (24%) with clinically insignificant PCa.
      In addition, 30 (34.1%) of the 88 patients harboured non-organ-confined disease.
      Consequently, the contemporary Epstein criteria for clinically insignificant PCa
      were inaccurate in 24% of patients. CONCLUSIONS: The Epstein clinical
      insignificant PCa criteria may underestimate the true nature of prostate cancer
      in as many as 24% of European patients. Therefore, caution is advised when
      treatment decisions are based solely on these criteria.

PMID- 18083295
TI  - Editorial comment on: validation of the contemporary epstein criteria for
      insignificant prostate cancer in European men.

PMID- 18083296
TI  - The DSM-IV-TR definition of premature ejaculation and its impact upon the results
      of epidemiological studies.

PMID- 18083297
TI  - Editorial comment on: validation of the contemporary Epstein criteria for
      insignificant prostate cancer in European men.

PMID- 18083298
TI  - Phenotypic plasticity of Escherichia coli at initial stage of symbiosis with
      Dictyostelium discoideum.
AB  - We observed the change in the physiological state of Escherichia coli cells at
      the initial stage for establishing a new symbiotic relationship with
      Dictyostelium discoideum cells. For the physiological state, we monitored green
      fluorescence intensity due to a green fluorescent protein (GFP) gene integrated
      into the chromosome by flow cytometry (FCM). On co-cultivation of the two
      species, a new population of E. coli cells with increased GFP concentration
      appeared, and when the formation of mucoidal colonies housing the coexisting two
      species began, most E. coli cells were from the new population. Further
      experiments suggest that the physiological change is induced by interaction with
      D. discoideum cells and is reversible, although the processes of the changes in
      both directions seem to proceed gradually. The observed phenotypic plasticity,
      together with natural selection under a co-cultivation environment, may be
      important for leading to the evolution of a new symbiotic system.

PMID- 18083299
TI  - Delay-induced model for tumor-immune interaction and control of malignant tumor
      growth.
AB  - The paper deals with the qualitative analysis of the solutions of a system of
      delay differential equations describing the interaction between tumor and immune
      cells. The asymptotic stability of the possible steady states is showed and the
      occurrence of limit cycle of the system around the interior equilibrium is proved
      by the application of Hopf bifurcation theorem by using the delay as a
      bifurcation parameter. The length of the delay parameter for preserving stability
      of the system is also estimated, which gives the idea about the mode of action
      for controlling oscillations in malignant tumor cell growth. The theoretical and
      numerical outcomes have been supported through experimental results from
      literatures. This approach gives new insight of modeling tumor-immune
      interactions and provides significant control strategies to overcome the large
      oscillations in tumor cells.

PMID- 18083300
TI  - Auto-regulation of estrogen receptor subtypes and gene expression profiling of
      17beta-estradiol action in the neuroendocrine axis of male goldfish.
AB  - Auto-regulation of the three goldfish estrogen receptor (ER) subtypes was
      examined simultaneously in multiple tissues, in relation to mRNA levels of liver
      vitellogenin (VTG) and brain transcripts. Male goldfish were implanted with a
      silastic implant containing either no steroid or 17beta-estradiol (E2) (100
      microg/g body mass) for one and seven days. Liver transcript levels of ERalpha
      were the most highly up-regulated of the ERs, and a parallel induction of liver
      VTG was observed. In the testes (7d) and telencephalon (7d), E2 induced ERalpha.
      In the liver (1d) and hypothalamus (7d) ERbeta1 was down-regulated, while ERbeta2
      remained unchanged under all conditions. Although aromatase B levels increased in
      the brain, the majority of candidate genes identified by microarray in the
      hypothalamus (1d) decreased. These results demonstrate that ER subtypes are
      differentially regulated by E2, and several brain transcripts decrease upon short
      term elevation of circulating E2 levels.

PMID- 18083301
TI  - Infusion of oxytocin induces successful delivery in prostanoid FP-receptor
      deficient mice.
AB  - The dramatic increase of oxytocin (OT) receptor (OTR) in the myometrium as well
      as circulating progesterone withdrawal has been thought to be the most important
      factor in the induction and accomplishment of parturition since delivery fails in
      prostaglandin F2alpha receptor (FP) knockout (FP KO) mice. The expression levels
      of OTR mRNA/protein were not dramatically increased in the near-term uteri of FP
      KO mice. However, OT-induced myometrial contractions and the concentration
      response curves in FP KO in vitro were almost similar to those in wild-type (WT)
      mice. OT-infusion (0.3 U/day) enabled FP KO mice to experience successful
      delivery, and furthermore the duration until the onset was hastened by a higher
      dose of OT (3 U/day). The plasma progesterone levels of FP KO females were
      maintained at high levels, but decreased during labor by OT-infusion (3 U/day).
      These results suggest that OT has potentials to induce strong myometrial
      contractions in uterus with low expression levels of OTR and luteolysis in ovary,
      which enabled FP KO females to undergo successful delivery.

PMID- 18083302
TI  - Experience of recombinant activated factor VII (NovoSeven) in the operating
      theatre and intensive care unit for the management of intracranial bleeding in
      nonhaemophilic patients.
AB  - OBJECTIVE: Intracranial haemorrhage (ICH) is associated with high morbidity and
      mortality. Our aim was to explore the use of recombinant activated factor VII
      (rFVIIa NovoSeven Novo Nordisk, A/S, Bagsvaerd, Denmark) for the management of
      ICH in the operating theater and intensive care unit. PATIENTS AND METHODS: We
      reviewed all the records of nonhaemophilic patients entered into the
      haemostasis.com database who received rFVIIa for ICH. RESULTS: Sixteen suitable
      patients were identified (mean age: 23.3 years; range: 1-58 years). The total
      dose of rFVIIa administered ranged from 31 to 270 microg/kg. Indications were
      stabilization of ICH (n=6), control of peri- or post-operative haemorrhage
      associated with neurosurgical procedures (n=8), or correction of coagulopathy
      prior to neurosurgical intervention (n=2). The majority (13/16 [81.25%]) required
      one dose of rFVIIa. A clinical effect (stabilization of bleed, reduction of peri-
      or post-operative haemorrhage, or prevention of excessive blood loss during
      neurosurgery) was seen in 14/16 (87.5%) patients. Some improvement in coagulation
      status was noted. No thromboembolic events were reported. One patient experienced
      massive elevation of D-dimer levels-an effect possibly due to rFVIIa. Two
      patients suffered adverse events unrelated to rFVIIa. Six deaths occurred, all
      attributable to underlying brain injury. CONCLUSION: This observational study
      suggests that rFVIIa is of value for the management of ICH in nonhaemophilic
      patients secondary to a range of aetiologies. These findings justify further
      investigation.

PMID- 18083303
TI  - The involvement of granulocytes in spontaneous regression of Walker 256
      carcinoma.
AB  - We described before that oxidative burst of granulocytes is cytotoxic for
      melanoma B16F10 and for Walker 256 carcinoma (W256). Therefore, we assumed that
      granulocytes could also be important mechanism of the host defence against
      tumour. In current study we report massive granulocyte infiltration at the site
      of W256 transplanted in the hind limb of Sprague-Dawley associated with
      spontaneous tumour regression observed for 22/25 rats (87%). Peripheral blood
      granulocytes of these animals were highly cytotoxic for W256 cells cultured in
      vitro. After the tumour disappearance the inflammatory oxidative burst of the
      granulocytes ended. Distraction of granulocytes from the tumour by s.c. Sephadex
      injection decreased the incidence of the W256 regression to only 7/25 animals
      (30%). These results suggest that innate immunity based on immune competent
      granulocytes may be the cause of well known phenomenon of spontaneous regression
      of W256 carcinoma.

PMID- 18083305
TI  - Interactions of NO2 with sewage sludge based composite adsorbents.
AB  - Interactions of NO2 present in most air were analyzed at room temperature on
      composite sewage sludge-derived adsorbents. They consist of carbonaceous and
      inorganic phases with the majority of the latter. The adsorption capacity was
      evaluated using the dynamic breakthrough experiments. The materials before and
      after NO2 exposure were characterized using adsorption of nitrogen, thermal
      analysis and FTIR. The results showed differences in the surface activities of
      sludge-derived materials towards immobilization and reduction of nitric dioxide.
      Nitrates and nitrite are the main products of surface reactions. This is linked
      to the presence of active oxides and hydroxides, which are formed when the
      surface is exposed to water. The highest activity of the sample pyrolyzed at 650
      degrees C is owing to the high content of those species formed as a result of
      decomposition of inorganic salts (likely chlorides, sulfates and phosphates)
      during thermal treatment. When sludge is pyrolyzed at 950 degrees C those oxides
      are engaged in stable mineral phases formed in solid-state reactions, which
      limits the surface activity towards NO2 retention. The reactivity of the high
      temperature pyrolyzed samples can be linked to the physical adsorption of water.
      In a water film nitrous and nitric acid can be formed and they can further react
      with inorganic and carbonaceous phases to the limited extent.

PMID- 18083304
TI  - Imatinib for hepatocellular cancer--focus on pharmacokinetic/pharmacodynamic
      modelling and liver function.
AB  - The effects of imatinib are partly mediated by the inhibition of platelet-derived
      growth factor (PDGF), which is highly expressed in the liver. In this phase-I/II
      trial pharmacokinetic parameters of imatinib given for hepatocellular cancer were
      similar to those previously derived from CML patients. The AUC of N-desmethyl
      imatinib depended on liver function; the metabolism of imatinib was otherwise
      comparable to other populations. During short-termed imatinib treatment (4 weeks,
      400 mg/d), plasma PDGF significantly decreased. The AUC of N-desmethyl-imatinib
      could best be attributed to the pharmacodynamic effect of PDGF inhibition (r=
      0.679 [95% CI: -0.917 to -0.0868], p=0.031).

PMID- 18083306
TI  - Sex-dependent neurofunctional predictors of long-term maintenance of visual word
      learning.
AB  - A previous study has revealed sex-dependent neurofunctional predictors of visual
      word learning [C. Chen, G. Xue, Q. Dong, Z. Jin, T. Li, F. Xue, L. Zhao, Y. Guo,
      Sex determines the neurofunctional predictors of visual word learning,
      Neuropsychologia 45 (2007) 741-747]. The present study aimed to extend that study
      to investigate sex-dependent neurofunctional predictors of long-term maintenance.
      Twenty-three Chinese college students trained in the previous study were followed
      up twice: immediately (T1) and 6 months after the training (T2). At both T1 and
      T2, subjects were tested with the simultaneously presented same-different
      judgment task. Compared with the T1 performance, subjects (both males and
      females) showed a small but significant amount of forgetting (i.e., longer
      reaction times) at T2. Consistent with our hypothesis, males' performance at both
      T1 and T2 was predicted by the pre-training left-lateralized fusiform activation,
      whereas females' performance was predicted by symmetrical bilateral fusiform
      activation.

PMID- 18083307
TI  - Effect of anti-NGF antibodies in a rat tibia fracture model of complex regional
      pain syndrome type I.
AB  - Tibia fracture in rats evokes chronic hindpaw warmth, edema, allodynia, and
      regional osteopenia resembling the clinical characteristics of patients with
      complex regional pain syndrome type I (CRPS I). Nerve growth factor (NGF) has
      been shown to support nociceptive and other types of changes found in neuropathic
      pain models. We hypothesized that anti-NGF antibodies might reduce one or more of
      the CRPS I-like features of the rat fracture model. For our studies one distal
      tibia of each experimental rat was fractured and casted for 4 weeks. The rats
      were injected with anti-NGF or vehicle at days 17 and 24 post-fracture.
      Nociceptive testing as well as assessment of edema and hindpaw warmth were
      followed during this period. Molecular and biochemical techniques were used to
      follow cytokine, NGF and neuropeptide levels in hindpaw skin and sciatic nerves.
      Lumbar spinal cord Fos immunostaining was performed. Bone microarchitecture was
      measured using microcomputed tomography (microCT). We found that tibia fracture
      upregulated NGF expression in hindpaw skin and tibia bone along with sciatic
      nerve neuropeptide content. We also found nociceptive sensitization, enhanced
      spinal cord Fos expression, osteopenia and enhanced cytokine content of hindpaw
      skin on the side of the fracture. Anti-NGF treatment reduced neuropeptide levels
      in sciatic nerve and reduced nociceptive sensitization. There was less spinal
      cord Fos expression and bone loss in the anti-NGF treated animals. Conversely,
      anti-NGF did not decrease hindpaw edema, warmth or cytokine production.
      Collectively, anti-NGF reduced some but not all signs characteristic of CRPS
      illustrating the complexity of CRPS pathogenesis and NGF signaling.

PMID- 18083308
TI  - Evaluation of an enzyme-linked immunosorbent assay for the serological diagnosis
      of Neospora caninum infection in sheep and determination of the apparent
      prevalence of infection in New Zealand.
AB  - Neospora caninum has recently been shown to be a cause of abortions of sheep in
      New Zealand. A commercially available enzyme-linked immunosorbent assay (ELISA)
      was validated for use in sheep with sera from experimentally infected sheep. A
      cut-off threshold was established that demonstrated sero-conversion between 7 and
      14 days post-infection. Higher inocula led to earlier sero-conversion. This ELISA
      was applied to 640 sera collected from rams across New Zealand and 0.625% (+/
      0.61%) (4/640) were shown to be serologically positive. The four positive sera
      were also demonstrated to be positive by indirect fluorescent antibody test
      (IFAT). The ELISA evaluated here lends itself more readily to large-scale
      investigations than IFAT. The low background of N. caninum infection in the New
      Zealand sheep population suggests that N. caninum abortions could be more easily
      diagnosed by serological means than in populations with higher background sero
      prevalence.

PMID- 18083309
TI  - Climate changes and suitability for the ticks Amblyomma hebraeum and Amblyomma
      variegatum (Ixodidae) in Zimbabwe (1974-1999).
AB  - The spread of Amblyomma hebraeum has been reported in Zimbabwe. At the same time
      there was little or no spread in the distribution of Amblyomma variegatum. This
      paper examines the climatic cycles and their trends in the period 1974-1999 with
      a view to explaining the abiotic causes of this spread, and of forecasting the
      likely tendency in climate suitability for both tick species. An annual data-set
      of rainfall and air temperature was used as a source for climate, together with a
      habitat-modeling algorithm to estimate climate suitability for both ticks. Long
      term suitable habitat for A. hebraeum exists mainly in the south and southeast of
      the country. Areas of adequate habitat for A. variegatum exist across the
      country, between approximately 17 degrees S and 18.5 degrees S, and are most
      suitable in regions of the northwest. The climate niches of the two species
      differ, and account for their almost allopatric distributions, as observed in the
      duration and intensity of the dry period and in total annual rainfall. Cyclic
      changes in both temperature and rainfall drive the periodic modifications in the
      distributions of the ticks. More intense periods of drought in the highveld,
      drive the expansion of A. hebraeum in this region. Temperature does not have any
      effect on the tendency in this area. Areas in south and southeast show a trend
      towards an increase in climatic suitability because of an increase in
      temperature. Zones in which habitat suitability is increasing for A. variegatum
      are restricted to the northwestern parts of the country, because warmer
      temperatures and a slight decrease in the intensity of the dry season. The
      progressive increase in temperatures seems to be forcing the dispersion of A.
      variegatum towards areas outside of zones that have a prolonged dry period. On
      the other hand A. hebraeum is compelled to spread northwards, following areas
      with adequate rainfall patterns, but halted by temperature limits and perhaps
      competition with A. variegatum. Without adequate control measures, invasive waves
      of A. hebraeum may occur over a background swell of northward expansion.

PMID- 18083310
TI  - In vitro cultivation of a newly recognized Babesia sp. in dogs in North Carolina.
AB  - A novel large Babesia sp. from an infected dog was cultivated in vitro by
      microaerophilous stationary phase culture methodology. A primary culture
      initiated in enriched RPMI-1640 medium supplemented with 40% canine serum and
      incubated in a 2% oxygen environment supported parasite growth in vitro.
      Subsequent subcultures into enriched HL-1 medium with 20% fetal bovine serum also
      supported parasite propagation. Cultures were successfully introduced to 5%
      carbon dioxide in air atmosphere at passage 4. To date, the parasites have been
      continuously cultured through 35 passages, although the parasitemias are low,
      ranging from 0.2 to 0.3%. Parasites cultured in RPMI with canine serum were
      cryopreserved and successfully recovered from liquid nitrogen storage. The small
      subunit ribosomal rRNA gene sequence was identical in blood-derived and culture
      derived parasites, differing in a single base position from the previously
      reported sequence for this Babesia sp. The ultrastructure of the parasite was
      consistent with that of other large Babesia spp., except that the spherical body
      contained numerous round particles unlike the inclusions previously described in
      Babesia spp.

PMID- 18083311
TI  - Delta 9-tetrahydrocannabinol-induced catalepsy-like immobilization is mediated by
      decreased 5-HT neurotransmission in the nucleus accumbens due to the action of
      glutamate-containing neurons.
AB  - Delta(9)-tetrahydrocannabinol (THC) has been reported to induce catalepsy-like
      immobilization, but the mechanism underlying this effect remains unclear. In the
      present study, in order to fully understand the neural circuits involved, we
      determined the brain sites involved in the immobilization effect in rats. THC
      dose-dependently induced catalepsy-like immobilization. THC-induced catalepsy
      like immobilization is mechanistically different from that induced by haloperidol
      (HPD), because unlike HPD-induced catalepsy, animals with THC-induced catalepsy
      became normal again following sound and air-puff stimuli. THC-induced catalepsy
      was reversed by SR141716, a selective cannabinoid CB(1) receptor antagonist.
      Moreover, THC-induced catalepsy was abolished by lesions in the nucleus accumbens
      (NAc) and central amygdala (ACE) regions. On the other hand, HPD-induced
      catalepsy was suppressed by lesions in the caudate putamen (CP), substantia nigra
      (SN), globus pallidus (GP), ACE and lateral hypothalamus (LH) regions. Bilateral
      microinjection of THC into the NAc region induced catalepsy-like immobilization.
      This THC-induced catalepsy was inhibited by serotonergic drugs such as 5-hydroxy
      L-tryptophan (5-HTP), a 5-HT precursor, and 5-methoxy-N,N-dimethyltryptamine (5
      MeODMT), a 5-HT receptor agonist, as well as by anti-glutamatergic drugs such as
      MK-801 and amantadine, an N-methyl-d-aspartate (NMDA) receptor antagonist. THC
      significantly decreased 5-HT and glutamate release in the NAc, as shown by in
      vivo microdialysis. SR141716 reversed and MK-801 inhibited this decrease in 5-HT
      and glutamate release. These findings suggest that the THC-induced catalepsy is
      mechanistically different from HPD-induced catalepsy and that the catalepsy-like
      immobilization induced by THC is mediated by decreased 5-HT neurotransmission in
      the nucleus accumbens due to the action of glutamate-containing neurons.

PMID- 18083312
TI  - Erectile dysfunction in male heroin users, receiving methadone and buprenorphine
      maintenance treatment.
AB  - Erectile dysfunction (ED) is common among people in treatment for heroin
      addiction. The purpose of the study was to examine the frequency of ED among
      methadone and buprenorphine maintenance therapy patients, and to identify factors
      associated with ED. Patients - recruited from 7 centres in Italy - underwent: (i)
      a structured interview on socio-demographic characteristics, drug use and sexual
      behaviour; (ii) IIEF-15 test, a test of sexual function; (iii) Zung test for
      depression. The study included 201 males: 42% were on methadone maintenance, 58%
      were on buprenorphine. Overall, 58% reported no ED, 24% reported mild to moderate
      ED, and 18% severe ED. In univariate analysis buprenorphine patients had less ED
      than methadone patients (p=0.0135). Subjects living with a partner had less ED
      than others (p=0.0018). More depressed subjects had more ED (p<0.001).
      Heterosexual patients reported less ED than homo/bisexual patients (p=0.0427),
      and partner's use of heroin was associated with more ED (p=0.0078). The
      significant univariate predictors were entered into a cumulative logit model.
      Living with a sexual partner was associated with a lower likelihood of ED, while
      depression, having a sexual partner with a history of drug use and not having a
      steady partner were associated with a greater likelihood of ED. The significant
      association between treatment and ED which appeared in univariate analysis (with
      buprenorphine patients reporting less ED than methadone patients) was not
      confirmed by the multivariate analysis. Both psychological and social factors
      were associated with ED which is an important problem for many males in methadone
      and buprenorphine treatment.

PMID- 18083313
TI  - Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated
      liposomes.
AB  - We and a Dutch group reported that "empty" PEGylated liposomes (approximately 100
      nm) lose their long-circulating characteristic when they are administrated twice
      in the same animal with certain intervals (referred to as the accelerated blood
      clearance (ABC) phenomenon). Very recently, we showed that anti-PEG IgM, induced
      by the first dose of "empty" PEGylated liposomes, is responsible for inducing the
      phenomenon, based on the observation that IgM thus produced selectively binds to
      the surface of subsequently injected PEGylated liposomes, leading to substantial
      complement activation. It is generally believed that nanocarriers coated with a
      polymer, such as PEG, have no or lower immunogenicity. However, the results
      indicated evidence that unexpected immune responses occur even to such polymer
      coated liposomes. Such immunogenicity of "empty" liposomes presents a serious
      concern in the development of liposomal formulations and their use in the clinic.
      In addition, through series of our studies, it was demonstrated that the
      magnitude of the ABC phenomenon depends on the physicochemical property of
      injected liposomes as a first dose, time interval between injection, lipid dose
      and drug-encapsulation.

PMID- 18083314
TI  - Disodium norcantharidate-loaded poly(epsilon-caprolactone) microspheres II.
      Modification of morphology and release behavior.
AB  - Disodium norcantharidate (DSNC)-loaded poly(epsilon-caprolactone) (PCL)
      microspheres were prepared by s/o/w solvent evaporation technique, and their
      morphology and drug release behavior were modified by adding NaCl (3, 6 and 9%)
      in the continuous phase during the preparation. The addition of NaCl decreased
      the water influx into the emulsion droplets and the porosity of the resultant
      microspheres. Higher NaCl concentration resulted in smaller particle size, lower
      density and higher drug loading of the microspheres. Despite higher drug loading
      and smaller particle size, the microspheres prepared with NaCl in the continuous
      phase exhibited slower drug release. The modification of the release profiles was
      correlated with the changes in the surface and internal morphology of the
      microspheres. Therefore, by adding NaCl in the continuous phase during the
      preparation, both morphology and release behavior of the microspheres can be
      modified to a certain extent.

PMID- 18083315
TI  - Panax ginseng ginsenoside-Rg2 protects memory impairment via anti-apoptosis in a
      rat model with vascular dementia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenosides, the major active ingredients of
      Panax ginseng, produce a variety of pharmacological or physiological responses
      with effects on the central and peripheral nervous systems. AIM OF THE STUDY: In
      this report, we investigated the effects of ginsenoside Rg2 on cerebral ischemia
      reperfusion induced impairment of neurological responses, memory and caudate
      putamen neuronal apoptosis in a vascular dementia (VD) rat model. MATERIALS AND
      METHODS: Neurological evaluation was performed 24h after reperfusion and Y-maze
      memory performance was assessed at 48 h after reperfusion. Immunocytochemical
      techniques were employed to check the protein expression of BCL-2, BAX, heat
      shock protein 70 and P53, which are related with cell apoptosis. RESULTS:
      Neurological responses and memory ability of the ginsenoside Rg2 or nimodipine
      groups improved significantly compared with the VD group. The expression of BCL-2
      and HSP70 were decreased, while BAX and P53 were increased in the VD model. The
      expression of BCL-2 and HSP70 proteins were increased, while BAX and P53
      decreased after ginsenoside Rg2 (2.5, 5 and 10mg/kg) and nimodipine (50
      microg/kg) treatment compared with the VD group. The study suggests that
      ginsenoside Rg2 improved neurological performance and memory ability of VD rats
      through mechanisms related to anti-apoptosis. CONCLUSIONS: The capacity for
      ginsenoside Rg2 to modulate the expression of apoptotic related proteins suggests
      that ginsenoside Rg2 may represent a potential treatment strategy for vascular
      dementia or other ischemic insults.

PMID- 18083316
TI  - Dry sex in Suriname.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dry sex refers to the use of plants to dry and
      contract the vagina, a popular practice in Africa that damages vaginal tissue and
      facilitates the spread of sexually transmitted diseases. Here we show that dry
      sex practices are not limited to Africa. Afro-Surinamese women frequently use
      genital steam baths that contain drying and tightening herbs. AIM OF THE STUDY:
      To assess the possible health consequences of this tradition, we quantified the
      diversity and trade in steam-bath ingredients and described the reasons why
      Surinamese women use them. MATERIALS AND METHODS: We collected botanical vouchers
      of steam-bath herbs, carried out a market survey and interviewed 140 women who
      used these baths. RESULTS: No less than 177 different plant species were employed
      in vaginal steam baths, not only for dry sex, but also to cleanse the uterus
      after childbirth and menstruation. Prohibiting the use of these baths is not an
      option. Moreover, they may save lives by preventing womb infection and puerperal
      fever. CONCLUSIONS: The lively trade in steam-bath herbs plays a role in the
      rapid increase in HIV among Surinamese citizens and migrants. We also have
      reasons to believe that dry-sex practices are more widespread in the Caribbean
      than previously thought.

PMID- 18083317
TI  - Dietary restriction by bacterial deprivation increases life span in wild-derived
      nematodes.
AB  - Dietary restriction is known to promote longevity in a variety of eukaryotic
      organisms. Most studies of dietary restriction have been performed on animals
      bred for many generations under conditions that differ substantially from their
      natural environment, raising the possibility that some apparent beneficial
      effects of dietary restriction are due to adaptation to laboratory conditions. To
      address this question in an invertebrate model, we determined the effect of
      dietary restriction by bacterial deprivation on life span in five different wild
      derived Caenorhabditis elegans strains and two strains of the related species
      Caenorhabditis remanei. Longevity was enhanced in each of the wild-derived C.
      elegans strains, in most cases to a degree similar to that observed in N2, the
      standard laboratory strain. Both strains of C. remanei were substantially longer
      lived any of the C. elegans isolates, produced larger brood sizes, and retained
      the ability to produce offspring for a longer period of time. Dietary restriction
      failed to increase mean life span in one C. remanei isolate, but significantly
      increased the maximum life span of both C. remanei strains. Thus, we find no
      evidence that adaptation to laboratory conditions has significantly altered the
      aging process in C. elegans under either standard or food-restricted conditions.

PMID- 18083318
TI  - Adipose tissue-specific PPARgamma deficiency increases resistance to oxidative
      stress.
AB  - The nuclear hormone receptor peroxisome proliferator activated receptor gamma
      (PPARgamma) critically regulates adipogenesis and lipogenesis. Obesity is closely
      associated with increased oxidative stress, and pharmacological activation of
      PPARgamma by its ligands significantly suppresses oxidative stress in cultured
      adipocytes. On the other hand, a PPARgamma2(Pro12Ala) polymorphism, which
      decreases receptor transcription activity, is associated with lower body mass
      index and increased insulin sensitivity in humans. This mutation is also found to
      be positively associated with increased human lifespan. Here we show that adipose
      tissue-specific PPARgamma heterozygous mice, which exhibit significant
      improvement in insulin sensitivity in skeletal muscle, show increased resistance
      to paraquat-induced oxidative stress. The enhanced oxidative stress tolerance is
      associated with significant upregulation of antioxidant genes in white adipose
      tissue and skeletal muscle whereas prooxidant genes are not changed. This is also
      associated with a significant increase in adipose tissue of Foxo3a, a
      transcription factor that is known to regulate clearance of reactive oxygen
      species. Consistently, Foxo3a dependent genes are significantly upregulated in
      adipose tissue. These data implicate adipose tissue PPARgamma in the regulation
      of oxidative stress, which may underlie extended lifespan in humans bearing
      PPARgamma2(Pro12Ala) mutation.

PMID- 18083319
TI  - Evaluation of cartilage defect at medial femoral condyle in early osteoarthritis
      of the knee.
AB  - OBJECTIVE: The purpose of this study was to evaluate cartilage defect at medial
      femoral condyle on MRI in early osteoarthritis and to compare with early
      osteoarthritis with meniscal tear without clear cartilage defect. MATERIALS AND
      METHODS: Twelve patients with medial pain of the knee and cartilage defect
      without meniscal tear by MRI were studied for cartilage defect. There were two
      males and 10 females with cartilage defect, and they were between 42 and 61 years
      of age (average, 51.6). Fifteen patients with medial pain of the knee and
      meniscal tear and without clear cartilage defect had been studied as meniscal
      tear cases. There were five males and 10 females with meniscal tear, and they
      were between 45 and 61 years of age (average 54.5). In both groups, knee injuries
      by trauma and Kellgren radiographic grade III and IV osteoarthritis were
      excluded. We compared cartilage defect cases and meniscal tear cases by gender,
      age, medial meniscus displacement ratio from the edge of the tibial medial joint
      surface, femorotibial angle (FTA) and Mikulicz line. We measured medial meniscus
      displacement ratio by the proportion of medial meniscus lesion protruding from
      the edge of tibial medial joint surface to all the medial meniscus width on MRI.
      For the evaluation of Mikulicz line, we measured the score by the length from
      tibial medial joint surface to Mikulicz line to tibial plateau width. chi(2) Test
      was used for gender, and Mann-Whitney U test was used for age, medial meniscus
      displacement ratio, FTA and Mikulicz line. RESULTS: Statistically significant
      difference was not observed between cartilage defect cases and meniscal tear
      cases for age and gender. Medial meniscus displacement ratio was 13+/-12.3% in
      cartilage defect cases and 50.4+/-20.1% in meniscal tear cases. Medial meniscus
      displacement ratio in cartilage defect cases was significantly smaller than in
      meniscal tear cases (P=.0001). FTA was 174.9+/-2.2 degrees in cartilage defect
      cases and 178.3+/-4.8 degrees in meniscal tear cases. FTA in cartilage defect
      cases was significantly smaller than in meniscal tear cases (P=.00390). The score
      by the length from tibial medial joint surface to Mikulicz line to tibial plateau
      width was 35.8+/-11.8% in cartilage defect cases and 21.7+/-15.8% in meniscal
      tear cases. Mikulicz line in cartilage defect cases passes more laterally than in
      meniscal tear cases significantly (P=.0264). CONCLUSION: In this study, we
      reported cartilage defect cases at medial femoral condyle in the early
      osteoarthritis of the knee. We think that these cases were different from early
      osteoarthritis with meniscal tear in alignment of lower limb and onset mechanism.
      It is necessary to evaluate meniscus and cartilage in MRI when we diagnose middle
      aged patients with medial pain of the knee and without remarkable changes of X
      ray.

PMID- 18083320
TI  - Enrichment of cerebrospinal fluid samples on cell culture for enhancement of
      sensitivity of mumps and enterovirus detection by multiplex RT-PCR.
AB  - It has been demonstrated that the detection of enteroviruses and mumps virus
      nucleic acid in cerebrospinal fluid (CSF) specimens improves the management of
      the patients with aseptic meningitis. To determine the effect of overnight
      enrichment of mumps and enteroviruses in CSF samples on cell culture for
      increasing the sensitivity of viral detection, we developed a multiplex reverse
      transcriptase-polymerase chain reaction (RT-PCR). CSFs were collected from 100
      patients younger than 7 years. The samples were tested for the presence of
      enteroviruses and mumps virus by multiplex RT-PCR method. Negative samples in
      Multiplex RT-PCR were enriched for viral template RNAs by overnight culture of
      CSF samples on cells and followed by the optimized Multiplex RT-PCR. Overall, 35%
      of the CSF samples were positive for enteroviruses, whereas only 1% of CSF
      samples were positive for both viruses. After enriching in cell culture, 34% of
      the negative samples showed a positive polymerase chain reaction band for
      enteroviruses, and a 3% increase was observed for both viruses. The results
      showed that enrichment of viral template RNAs in cell culture can increase the
      sensitivity of the multiplex RT-PCR assay and provide a rapid and sensitive
      method for detection of viral infections.

PMID- 18083321
TI  - A systematic review of emergency care brief alcohol interventions for injury
      patients.
AB  - This article examines 14 studies that assessed the effectiveness of brief
      interventions (BIs) delivered to injury patients in emergency care settings. The
      aims were to review findings concerning the effectiveness of providing BI in
      these settings and to explore factors contributing to its effectiveness. Of the
      12 studies that compared pre- and post-BI results, 11 observed a significant
      effect of BI on at least some of the outcomes: alcohol intake, risky drinking
      practices, alcohol-related negative consequences, and injury frequency. Two
      studies assessed only post-BI results. More intensive interventions tended to
      yield more favorable results. BI patients achieved greater reductions than
      control group patients, although there was a tendency for the control group(s) to
      also show improvements. Five studies failed to show significant differences
      between the compared treatment conditions. Variations in the study protocol,
      alcohol-related recruitment criteria, screening and assessment methods, and
      injury severity limit the specific conclusions that can be drawn.

PMID- 18083322
TI  - Motivational enhancement therapy to improve treatment utilization and outcome in
      pregnant substance users.
AB  - Pregnant substance users can benefit significantly from substance abuse
      treatment, but treatment retention can be challenging. Two hundred pregnant
      substance users entering outpatient substance abuse treatment at one of four
      treatment programs were randomized to receive either three individual sessions of
      Motivational Enhancement Therapy for pregnant substance users (MET-PS) or the
      first three individual sessions normally provided by the program. All
      participants were encouraged to participate in all other treatment offered by the
      program. Outcome measures included treatment utilization according to clinic
      records, qualitative urine toxicology measures, and self-report of substance use.
      One hundred sixty-two (81%) participants completed the 1-month active phase.
      Participants attended 62% of scheduled treatment on average and reported
      decreased substance use during the first month of treatment, with no differences
      between MET-PS and treatment-as-usual (TAU) participants. There was some evidence
      that the efficacy of MET-PS varied between sites and that MET-PS might be more
      beneficial than TAU in decreasing substance use in minority participants. These
      results suggest that MET-PS is not more effective than TAU for pregnant substance
      users in general but that there might be particular subgroups or treatment
      programs for which MET-PS might be more or less effective than TAU.

PMID- 18083323
TI  - Prediction of aminoglycoside response against methicillin-resistant
      Staphylococcus aureus infection in burn patients by artificial neural network
      modeling.
AB  - OBJECTIVE: To predict the response of aminoglycoside antibiotics (arbekacin: ABK)
      against methicillin-resistant Staphylococcus aureus (MRSA) infection in burn
      patients after considering the severity of the burn injury by using artificial
      neural network (ANN). Predictive performance was compared with logistic
      regression modeling. METHODOLOGY: The physiologic data and some indicators of the
      severity of the burn injury were collected from 25 burn patients who received ABK
      against MRSA infection. A three-layered ANN architecture with six neurons in the
      hidden layer was used to predict the ABK response. The response was monitored
      using three clinical criteria: number of bacteria, white blood cell count, and C
      reactive protein level. Robustness of models was investigated by the leave-one
      out cross-validation. RESULTS: The peak plasma level, serum creatinine level,
      duration of ABK administration, and serum blood sugar level were selected as the
      linear input parameters to predict the ABK response. The area of the burn after
      skin grafting was the best parameter for assessing the severity of the burn
      injury in patients to predict the ABK response in the ANN model. The ANN model
      with the severity of the burn injury was superior to the logistic regression
      model in terms of predicting the performance of the ABK response. CONCLUSION:
      Based on the patients' physiologic data, ANN modeling would be useful for the
      prediction of the ABK response in burn patients with MRSA infection. Severity of
      the burn injury was a parameter that was necessary for better prediction.

PMID- 18083324
TI  - Paracoccidioides brasiliensis conidia recognize fibronectin and fibrinogen which
      subsequently participate in adherence to human type II alveolar cells:
      involvement of a specific adhesin.
AB  - We examined the ability of Paracoccidioides brasiliensis conidia to interact with
      fibronectin, fibrinogen and with A549 cells, in order to establish the nature of
      the molecules involved. Conidia bound to immobilized proteins in a concentration
      dependent manner. Antibodies against fibronectin and fibrinogen inhibited the
      fungal adherence to the corresponding proteins; as did laminin and fibronectin,
      but not fibrinogen when added in soluble form; however, the fibrinogen fragment D
      interfered with adhesion in a significant manner. Various monosaccharides and
      RGD/RGDS peptides had no effect on adherence to fibronectin or fibrinogen, while
      N-acetylneuraminic acid (NANA) abolished adherence to both proteins.
      Additionally, these proteins were detected on the surface of A549 cells.
      Inhibition assays showed a significant decrease in fungal adherence when A549
      cells were treated with anti-fibrinogen, anti-fibronectin antibodies and a
      purified adhesin of P. brasiliensis (32-kDa protein); or when conidia were
      treated with these soluble proteins, mAb anti-32-kDa protein, RGD peptides and
      NANA. These results suggest that fibrinogen and fibronectin facilitate the
      adherence of conidia to A549 cells probably through the interaction with adhesin
      type molecules or a sialic acid based recognition system. These interactions
      appear to play a role in the initial fungal attachment to the lung, and
      consequently, also in the pathogenesis of paracoccidioidomycosis.

PMID- 18083325
TI  - Residual brain infection in murine relapsing fever borreliosis can be
      successfully treated with ceftriaxone.
AB  - Like several other spirochetes, relapsing fever Borrelia can cause persistent
      infection of the central nervous system (CNS). By treating mice harboring
      residual Borrelia duttonii brain infection with the bacteriocidal, cell wall
      inhibiting antibiotic ceftriaxone, bacteria were cleared from the brain. This
      shows that the residual infection is not latent but actively growing.

PMID- 18083326
TI  - Parenting practices and childhood anxiety reporting in Mexican, Mexican American,
      and European American families.
AB  - Parenting practices reflecting over-control and lack of warmth and acceptance are
      associated with childhood anxiety in white non-Latino populations. In this study,
      we examined whether these parenting practices were related to childhood anxiety
      in Mexican-descent children. Mexican (M: n=46), Mexican American (MA: n=48), and
      European American (EA: n=47) families discussed three ambiguous, potentially
      anxiety provoking situations. Transcribed discussions were coded for parenting
      practices reflecting control and lack of warmth and acceptance. Controlling
      practices were associated with more anxiety for the M and EA groups and with less
      anxiety for the MA group. The MA parents generated more verbalizations indicative
      of control than the M parents and more verbalizations indicative of lack of
      warmth and acceptance than the EA parents. Implications for our understanding of
      anxiety development in Latino children are discussed.

PMID- 18083327
TI  - DA and Xiao-two giant and composite LTR-retrotransposon-like elements identified
      in the human genome.
AB  - We discovered two new complex elements while studying large genomic
      rearrangements and segmental duplications in the human genome. Both resemble
      bacterial composite DNA transposon Tn9, consisting of a core flanked by mobile
      elements, except that the flanking element is not a DNA transposon but instead is
      long terminal repeat retrotransposon-like with human endogenous retrovirus and
      satellite sequences. Based on the core size, we named them Xiao ( approximately
      30 kb) and DA ( approximately 280 kb), meaning small and big, respectively, in
      Chinese. Xiao originated from a 19p region encoding olfactory receptor 7E members
      after the human/ape divergence from Old World monkeys, while DA likely evolved
      from a Xiao by inserting approximately 200 kb of chimeric sequence from 16p and
      21q into the Xiao core, resulting in a target site duplication of 3.4 kb. DA/Xiao
      was identified in 30 loci on 12 chromosomes, and only DAs mediated
      intrachromosomal rearrangements, based on our reconstructed human-mouse-rat
      ancestral genome and the rhesus macaque genome.

PMID- 18083328
TI  - Comparative genomics of human-like Schistosoma japonicum genes indicates a
      putative mechanism for host-parasite relationship.
AB  - Schistosoma japonicum causes schistosomiasis in humans and livestock in the Asia
      Pacific region. We assembled more than 43,700 S. japonicum expressed sequence
      tags and conducted comparative genomic analyses between S. japonicum and its
      human host. Some schistosome genes showed exceptionally high similarity in
      nucleotide sequence to their human homologues, of which five exhibited anomalous
      phylogeny and human codon usage bias. The most plausible explanation for their
      presence is horizontal gene transfer from host to parasite. Functional evidence
      suggests that S. japonicum might exploit host endocrine and immune signals for
      cell development and maturation via these host-like genes.

PMID- 18083329
TI  - Therapeutic angiogenesis of bone marrow mononuclear cells (MNCs) and peripheral
      blood MNCs: transplantation for ischemic hindlimb.
AB  - We investigated bone marrow mononuclear cells (BM-MNCs) and peripheral blood
      mononuclear cells (PB-MNCs) for therapeutic angiogenesis in the ischemic
      hindlimb. BM-MNCs were isolated and injected into ischemic skeletal muscles in
      mice. Laser Doppler and histological evaluation were performed after the surgical
      procedure. Fifteen patients suffering from critical lower limb ischemia received
      subcutaneous injections of recombinant human granulocyte colony-stimulating
      factor (G-CSF) to mobilize progenitor cells, and PB-MNCs were harvested and
      transplanted directly into the ischemic limb. Endothelial cells derived from BM
      MNCs were plated, then induced to form three-dimensional networks by invading a
      Matrigel. Four weeks after implantation of BM-MNCs, laser Doppler analysis showed
      that the blood flow ratio was significantly increased (0.67 +/- 0.02 vs. 0.44 +/-
      0.02). Alkaline phosphatase and immunohistochemical analyses showed that
      capillary density was significantly increased (95.25 +/- 0.07% vs. 39.6 +/-
      0.04%). Two months after implantation of PB-MNCs, in both subgroups, ankle
      brachial index values, walking distance, pain scale, and transcutaneous oxygen
      pressure (TcO(2)) were significantly improved (p < 0.005). A total of six of 15
      limb ulcers of transplanted patients were healed after cell transplantation. BM
      MNC implantation was able to induce functional angiogenesis in mice ischemic
      hindlimb. This clinical trial shows that G-CSF-based PB-MNC transplantation is a
      feasible treatment for the ischemic hindlimb.

PMID- 18083330
TI  - Can the National Kidney Foundation guidelines for first-time arteriovenous
      fistula creation be met in underserved end-stage renal disease patients?
AB  - The aims of this study were to determine whether National Kidney Foundation (NKF)
      guidelines for native arteriovenous fistula (AVF) creation (at least 50% of all
      new end-stage renal disease [ESRD] patients and 40% of prevalent hemodialysis
      patients) could be met in an underserved population who presented in late stages
      of ESRD. We also sought to determine 1-year AVF patency rates and factors
      associated with early thrombosis. One hundred seventy-six patients underwent
      hemodialysis access surgery during the period 2003-2005 with a mean age of 51
      years. Sixty-two percent were male, and 48% had diabetes mellitus. Ultrasound
      vein mapping was performed in only 37%. Temporary central venous access was
      necessary in 109 patients (62%) due to late presentation. Of the 160 patients who
      were first-time access, 137 (86%) received a native AVF and 23 (14%) had an
      arteriovenous graft. There was a higher rate of AVF creation in males (91% vs.
      75% for females, p = 0.005). The 1-year primary patency was 90%. There were no
      differences in early thrombosis or 1-year patency rates with respect to gender,
      age, ethnicity, insurance status, presence of temporary access, or use of
      preoperative vein mapping. In an underserved population, NKF guidelines for
      native AVF for first-time access can be superseded with an excellent 1-year
      patency, despite late presentation.

PMID- 18083331
TI  - Subclavian artery revascularization: an outcome analysis based on mode of therapy
      and presenting symptoms.
AB  - Therapy for atherosclerotic occlusive subclavian arterial disease is undergoing a
      paradigm shift from open to endoluminal therapy. The aim of this study was to
      review the changing patterns of presentation and clinical outcomes based on
      presenting symptoms of subclavian artery revascularization. We performed a
      retrospective analysis of consecutive patients treated for symptomatic
      atherosclerotic occlusive subclavian arterial disease from 1992 through 2006.
      Mean follow-up was 4 years. One hundred fourteen patients with a mean age of 63
      years (range 33-89, 61% female) underwent 137 procedures. Of these, 89% had
      hypertension, 32% were diabetic, 69% had hyperlipidemia, and 13% had chronic
      renal insufficiency. Sixty-seven primary stent attempts (five technical failures)
      and 70 open (64 carotid-subclavian bypasses, six subclavian-carotid
      transpositions) were performed. No deaths occurred within the 30-day
      perioperative period. Fifty-seven percent of the patients presented with symptoms
      of arm ischemia: exertional pain (84%), rest pain (12%), and ulceration (4%). The
      assisted primary patency was 81 +/- 7% and 80 +/- 10% at 5 and 10 years,
      respectively. Symptoms resolved in all patients, and none required major or minor
      amputations. Freedom from recurrent arm symptoms was 71 +/- 8% and 71 +/- 10% at
      5 and 10 years, respectively. Twenty-five percent of the patients presented with
      a cardiac indication: preparation for a left internal mammary artery (IMA) bypass
      in 61% and recurrent cardiac ischemia in the remainder. The assisted primary
      patency was 97 +/- 6% at 5 years. No IMAs were abandoned in this group, and the
      freedom from recurrent cardiac symptoms related to IMA distribution was 79 +/-
      10% at 5 years. Eighteen percent of patients presented with posterior circulation
      symptoms secondary to vertebrobasilar disease. The assisted primary patency was
      100 +/- 0% and 100 +/- 0% at 5 and 10 years, respectively. Freedom from recurrent
      vertebrobasilar symptoms was 95 +/- 6% and 95 +/- 10% at 5 and 10 years,
      respectively. Subclavian artery revascularization is safe and effective, but long
      term outcomes are determined by the presenting symptomatology.

PMID- 18083332
TI  - Masson tumor as humeral artery aneurysm.
AB  - Intravascular papillary endothelial hyperplasia (Masson's vegetant
      hemangioendothelioma) is a rare condition affecting the arteries. In the
      literature, we did not find any reference to this lesion involving the humeral
      artery. We present a case of asymptomatic humeral artery vascular tumor due to
      this abnormality. A 58-year-old woman was admitted to our hospital with an
      asymptomatic pulsatile humeral artery mass. Echography revealed an increase in
      size in the last year. The tumor was removed, and the vascular segment was
      replaced by a segment of inverted cephalic vein. The findings of the pathological
      examination were compatible with intravascular papillary endothelial hyperplasia.
      At follow-up examination 5 months after the operation, the patient had no tumor,
      remained asymptomatic, and had preserved upper limb artery patency. This rare
      vascular lesion may be clinically and histopathologically mistaken for a
      malignant tumor. As the Masson tumor can be cured by complete surgical resection,
      it is important to get a correct diagnosis.

PMID- 18083333
TI  - Silicone-based vascular prosthesis: assessment of the mechanical properties.
AB  - We introduce a silicone-based vascular prosthesis that may be optimized in
      various ways. The current work describes the theoretical background, the
      fabrication process, and the mechanical properties of these new prostheses,
      allowing objectification and comparison of materials used in vascular surgery. A
      production process to coat polyester prostheses with silicone-rubber
      (polydimethylsiloxane, PDMS) was established. Further modifications (surface
      improvements, drug incorporation for release) can be performed wet-chemically.
      Measurement of the physical properties included longitudinal and circumferential
      stability and elasticity, suture retention strength and puncture resistance
      (tensile testing machine), permeability, and compliance (circulation model).
      Prostheses can be multiply coated with PDMS. Sufficiently low levels of
      permeability (<5 mL/cm(2)/min at 120 mm Hg) were achieved with a PDMS content >15
      mg/cm(2). Considering stability, elasticity, and compliance, prostheses with a
      silicone-rubber content of 15-20 mg/cm(2) are comparable to conventional,
      primarily tight prostheses. Coating with PDMS decreases suture retention strength
      and puncture resistance compared to conventional alloplastic materials (collagen
      coated polyester and expanded polytetrafluorethylene) materials. The silicone
      coating surrounds the passing threads ("self-sealing surface") and is resistant
      to clamping trauma. The complete measurement procedures described here allow for
      a comparison of new materials with conventional ones and allow the handling
      characteristics of implants to be objectified. The primarily tight, silicone
      coated prostheses can be compared to conventional bovine-coated materials without
      drawbacks regarding physical properties.

PMID- 18083334
TI  - Analysis of expansion patterns in 4-4.9 cm abdominal aortic aneurysms.
AB  - Our objective was to analyze the growth pattern of 4-4.9 cm infrarenal abdominal
      aortic aneurysms (AAAs). We used an observational, longitudinal, prospective
      study design. We followed 4-4.9 cm AAAs with 6-monthly abdominal computed
      tomographic (CT) scans (January 1988-August 2004). AAA growth was defined as an
      increase in aortic diameter > or =2 mm in each surveillance period. We
      established the aortic expansion pattern in AAA with three or more CT scans as
      continuous, discontinuous. The latter includes at least one period of nongrowth
      (<2 mm/6 months). We studied the influence of cardiovascular risk factors
      (CVRFs), comorbidity, and AAA anatomical characteristics using the chi-squared
      test, t-test, life tables, and Kaplan-Meier for statistical analysis. We included
      195 patients: 183 (93.8%) men, age 71 +/- 8.3 years (50-90). The follow-up period
      was 50 +/- 36.4 months (6.5-193.7). The growth pattern (n =131) was continuous in
      15 (11.5%) and discontinuous in 116 (88.5%) AAA. The mean expansion rate was
      higher in AAAs with continuous expansion (7.92 +/- 3.74 vs. 2.74 +/- 2.94
      mm/year, p < 0.0001). No CVRFs or comorbidity influenced the expansion pattern (p
      > 0.05). The eccentric thrombus was associated with a greater incidence of
      continuous growth (p = 0.05), with no influence of aortic calcification (p >
      0.1). The expansion of 4-4.9 cm AAA is mostly irregular and unpredictable. We
      have not found any modifiable risk factors which influence their growth pattern.
      The eccentric distribution of the thrombus is associated with continuous
      expansion.

PMID- 18083335
TI  - Multidetector computed tomographic angiography findings in a rare case of
      popliteal artery entrapment syndrome.
AB  - Popliteal artery entrapment syndrome (PAES) is a disorder of the young age group
      characterized by ischemia of the lower extremities due to an abnormal association
      between the popliteal artery and adjacent musculotendinous structures. Several
      underlying anatomical abnormalities causing this syndrome are described and
      classified. In this study, we present an unusual case of PAES along with
      multidetector computed tomographic angiography findings.

PMID- 18083336
TI  - Risk of stroke for carotid endarterectomy patients with contralateral carotid
      occlusion.
AB  - The role of a contralateral carotid occlusion in the appearance of neurological
      complications after carotid endarterectomy (CEA) operations is a matter of some
      debate. In the North American Symptomatic Carotid Endarterectomy Trial, the risk
      of perioperative stroke was found to be higher in patients with a contralateral
      carotid occlusion. In a literature survey in 2004, however, a significantly
      increased risk of perioperative stroke was found in only one out of 17 studies on
      contralateral carotid occlusion patients. We therefore examined the frequency of
      stroke in patients with contralateral carotid occlusion at our own institution
      and performed a meta-analysis based on 19 representative studies, including the
      data from our own institution. Out of 1,960 CEAs at the authors' institute, a
      significantly higher frequency of 5.6% compared to 2.1% (p = 0.012) for
      perioperative stroke risk was seen in patients with contralateral carotid
      occlusion compared to those without. The meta-analysis, based on 19 studies, also
      showed in 13,438 CEA operations a significantly higher perioperative stroke rate
      of 3.7% compared to 2.4% (p = 0.002) in the presence of a contralateral carotid
      occlusion. Nevertheless, due to the extremely poor outcomes of medically treated
      symptomatic patients, a surgical or endovascular procedure should be sought for
      these patients. Since the superiority of angioplasty/stent procedures has not yet
      been verified compared to surgical procedures in these patients, special
      indication for an endovascular procedure should also be taken into consideration.

PMID- 18083337
TI  - Risk factors and angiographic technical considerations to guide carotid
      intervention.
AB  - Carotid angioplasty and stenting (CAS) with embolic protection is currently
      accepted as treatment for patients considered to be at high risk for carotid
      endarterectomy (CEA). The purpose of this study was (1) to determine what
      proportion of patients treated with CEA would be categorized as "high" risk by
      currently accepted criteria, (2) to characterize preoperative angiographic
      findings in patients with carotid stenosis, and (3) to determine the potential
      technical challenges of CAS in these patients. Consecutive patients who underwent
      CEA from January 1999 through August 2004 prior to introduction of CAS at our
      institution were identified. Demographics, indications, perioperative
      complications, and deaths were reviewed. Published guidelines defining high risk
      for CEA were applied, and preoperative angiograms were examined for technical
      limitations to CAS. Two hundred and seventy-nine CEAs were performed in 259
      patients for asymptomatic carotid occlusive disease (57%), transient ischemic
      attacks (35%), or stroke (8%) during the study period. Of these, 35.5% (n = 99)
      would have met one or more high-risk criteria. Overall risks of perioperative
      stroke, myocardial infarction, and death were 1.1%, 2.2%, and 0.4% (n = 279),
      respectively, with a combined major complication rate of 3.3%. No difference in
      major complication rates was observed between standard-risk and high-risk
      patients. Preoperative angiograms were available for review in 83.5% of CEAs (n =
      233). The distribution of aortic arch configurations included types I (3.5%), IIa
      (39.5%), IIb (54.5%), and III (1.3%). Aortic arch anomalies were observed in
      15.5% (n = 35) of angiograms. There were 77.7% (n = 181) with one or more
      angiographic findings that would have increased the technical difficulty of CAS,
      but only 17.6% had relative angiographic contraindications to CAS. A significant
      proportion of patients with carotid stenosis previously managed with CEA would be
      categorized as high risk and considered potential candidates for CAS by currently
      accepted criteria. Based on preoperative angiography, technically challenging
      factors, some of which limit the ability to perform CAS, are common and should be
      anticipated when planning CAS.

PMID- 18083338
TI  - Octamer-binding transcription factor-1 gene is upregulated in primary varicose
      veins.
AB  - While the pathogenesis of varicose veins is assumed to be multifactorial,
      including the aging process, the etiology, especially in the very young, is
      strongly linked to genetics and is believed to be associated with improper
      development and regulation of venous tissue maturation. The aim of this study was
      to identify the genes whose expression is different in primary varicose veins
      compared to normal veins in the legs. To test this hypothesis, the differentially
      expressed gene technique was performed on a large-scale screen of mRNA from
      varicose and normal veins. Transcriptional products corresponding to cDNA were
      compared between the two vein types, and one gene showed the greatest
      differential expression between the samples in all sets of experiments, confirmed
      by reverse-transcriptase polymerase chain reaction. Octamer-binding transcription
      factor-1 gene (Oct-1) was upregulated in primary varicose veins. Therefore, we
      suggest that Oct-1 may play an important role in the development of primary lower
      extremity varicose veins.

PMID- 18083339
TI  - Hybrid laparorobotic debranching and endovascular repair of thoracoabdominal
      aortic aneurysm.
AB  - Surgical debranching and endovascular repair is an attractive hybrid approach in
      high-risk patients with thoracoabdominal aneurysms unsuitable for conventional
      open repair. Vascular laparorobotic technology is an evolving field in the
      treatment of aortoiliac and aneurysmal disease. Herein we present a case in which
      hybrid laparorobotic debranching and endovascular repair was performed in a
      patient with a symptomatic 7 cm thoracoabdominal aortic aneurysm extent III. The
      laparorobotic approach was utilized for iliac artery exposure and suturing of the
      proximal anastomosis of the debranching graft. The technique was also useful in
      limiting the extent of the abdominal incision in a patient with severe
      comorbidities. Advantages of computer-assisted robotic vascular reconstruction
      include a high-resolution three-dimensional field of view and technical precision
      for vascular dissection and anastomosis.

PMID- 18083340
TI  - Endovascular stent-graft repair of failed endovascular abdominal aortic aneurysm
      repair.
AB  - Despite high initial technical success, the long-term durability of endovascular
      abdominal aortic aneurysm repair (EVAR) continues to be a concern. Following
      EVAR, patients can experience endoleaks, device migration, device fractures, or
      aneurysm growth that may require intervention. The purpose of this study was to
      review all patients treated with secondary endovascular devices at our
      institution for failed EVAR procedures. Over an 8-year period, 988 patients
      underwent EVAR, of whom 42 (4.3%) required secondary interventions involving
      placement of additional endovascular devices. Data regarding patient
      characteristics, aneurysm size, initial device type, time until failure, failure
      etiology, secondary interventions, and outcomes were reviewed. The mean time from
      initial operation until second operation was 34.1 months. Failures included type
      I endoleaks in 38 patients (90.5%), type III endoleaks in two patients (4.8%),
      and enlarging aneurysms without definite endoleaks in two patients (4.8%). The
      overall technical success rate for secondary repair was 92.9% (39/42).
      Perioperative complications occurred in nine patients (21.4%), including wound
      complications (n = 6), cerebrovascular accident (CVA) (n = 1), foot drop (n = 1),
      and death (n = 1). Mean follow-up following secondary repair was 16.4 months
      (range 1-50). Eighty-six percent of patients treated with aortouni-iliac devices
      had successful repairs compared to 45% of patients treated with proximal cuffs.
      Ten patients (23.8%) had persistent or recurrent type I or type III endoleaks
      following revision. Of these, four had tertiary interventions, including two
      patients who had additional devices placed. Failures following EVAR occur in a
      small but significant number of patients. When anatomically possible,
      endovascular revision offers a safe means of treating these failures. Aortouni
      iliac devices appear to offer a more durable repair than the proximal cuff for
      treatment of proximal type I endoleaks. Midterm results indicate that these
      patients may require additional procedures but have a low rate of aneurysm
      related mortality. Longer-term follow-up is necessary to determine the durability
      of these endovascular revisions.

PMID- 18083341
TI  - Acute renal artery embolism: a case report and brief literature review.
AB  - Acute renal artery embolism is an uncommon clinical diagnosis. We present a case
      report of a patient who was treated with transcatheter thrombolysis and a
      literature review and discussion of this condition and its management.

PMID- 18083342
TI  - What we learned about trials from the European Carotid Stent Trials.

PMID- 18083343
TI  - Validation of a glottographic measure of vocal attack.
AB  - The speed with which the vocal folds adduct to the midline is considered an
      important variable in the etiology of some voice disorders and may also be a
      meaningful indicator of central or peripheral neural dysfunction. It is proposed
      that the time lag between the rise of the sound pressure (SP) and
      electroglottographic (EGG) signals, measured at the onset of phonation, provides
      a useful index of vocal attack time. This report describes the experimental
      validation of this measure, whereby the SP and EGG signals were recorded
      synchronously with high-speed videoendoscopy, from which a digital kymogram was
      generated. It is shown that, after appropriate signal processing, the intersignal
      time delay provides a potentially useful measure that varies with vocal attack
      characteristics. The proposed method calls for no invasive procedures and relies
      on signals that are routinely obtained in most clinical settings. Unlike acoustic
      "rise time" measures of voice onset, the glottographic measure involves no
      operator intervention, requires no arbitrary decisions about measurement points,
      and may be accomplished quickly and automatically on any personal computer.

PMID- 18083344
TI  - Region competition based active contour for medical object extraction.
AB  - In this paper, a probabilistic and level set model for three-dimensional medical
      object extraction is proposed, which is called region competition based active
      contour. The algorithms are derived by minimizing a region based probabilistic
      energy function and implemented in a level set framework. An additional speed
      controlling term makes the active contour quickly convergent to the actual
      contour on strong edges, whereas a probabilistic model makes the active contour
      performing well for weak edges. Prior knowledge about the initial contour and the
      probabilistic distribution contributes to more efficient extraction. The
      developed model has been applied to a variety of medical images, from CTA and MRA
      of the coronary to rotationally scanned and real-time three-dimensional
      echocardiography images of the mitral valve. As the results show, the algorithm
      is fast, convergent, adapted to a broad range of medical objects and produces
      satisfactory results.

PMID- 18083345
TI  - Endogenous RGS proteins attenuate Galpha(i)-mediated lysophosphatidic acid
      signaling pathways in ovarian cancer cells.
AB  - Lysophosphatidic acid is a bioactive phospholipid that is produced by and
      stimulates ovarian cancer cells, promoting proliferation, migration, invasion,
      and survival. Effects of LPA are mediated by cell surface G-protein coupled
      receptors (GPCRs) that activate multiple heterotrimeric G-proteins. G-proteins
      are deactivated by Regulator of G-protein Signaling (RGS) proteins. This led us
      to hypothesize that RGS proteins may regulate G-protein signaling pathways
      initiated by LPA in ovarian cancer cells. To determine the effect of endogenous
      RGS proteins on LPA signaling in ovarian cancer cells, we compared LPA activity
      in SKOV-3 ovarian cancer cells expressing G(i) subunit constructs that are either
      insensitive to RGS protein regulation (RGSi) or their RGS wild-type (RGSwt)
      counterparts. Both forms of the G-protein contained a point mutation rendering
      them insensitive to inhibition with pertussis toxin, and cells were treated with
      pertussis toxin prior to experiments to eliminate endogenous G(i/o) signaling.
      The potency and efficacy of LPA-mediated inhibition of forskolin-stimulated
      adenylyl cyclase activity was enhanced in cells expressing RGSi G(i) proteins as
      compared to RGSwt G(i). We further showed that LPA signaling that is subject to
      RGS regulation terminates much faster than signaling thru RGS insensitive G
      proteins. Finally, LPA-stimulated SKOV-3 cell migration, as measured in a wound
      induced migration assay, was enhanced in cells expressing Galpha(i2) RGSi as
      compared to cells expressing Galpha(i2) RGSwt, suggesting that endogenous RGS
      proteins in ovarian cancer cells normally attenuate this LPA effect. These data
      establish RGS proteins as novel regulators of LPA signaling in ovarian cancer
      cells.

PMID- 18083347
TI  - Organic and inorganic calcium antagonists inhibit veratridine-induced
      epileptiform activity in CA3 neurons of the guinea pig.
AB  - Veratridine is believed to cause epileptiform discharges via its effects on
      sodium channels. We addressed the question whether calcium currents, known to
      contribute to the generation of paroxysmal depolarization shifts (PDS) in most
      models of epilepsies, also contribute to veratridine-induced epileptiform
      activity. Therefore, we recorded from CA3 neurons (n=50) of veratridine-treated
      hippocampal slices and analyzed the effects of two calcium antagonists.
      Veratridine (0.5-1.0 microM) elicited spontaneous epileptiform bursts, paroxysmal
      depolarization shifts (PDS) lasting 100-300 ms, and depolarizations (LD) lasting
      up to several minutes. Most often PDS directly preceded LD which resulted in
      typical composite depolarizations termed veratridine-induced complexes (VC). VC
      persisted even in the presence of CNQX and APV (25 micromol/l, both), or in
      nominally calcium-free saline, revealing the non-synaptic nature of these
      potentials. Cobalt (1-2mM) abolished VC within minutes, but allowed LD type-like
      potentials to be elicited by depolarizing current pulses. Verapamil (50 microM)
      also diminished or abolished amplitudes of VC. All inhibitory effects of cobalt
      and verapamil were at least partly reversible. Due to the effects of both calcium
      antagonists we conclude that veratridine-induced epileptiform activity depends
      not only on sodium, but also on calcium currents.

PMID- 18083348
TI  - Dual-isotope SPECT imaging of striatal dopamine: first episode, drug naive
      schizophrenic patients.
AB  - OBJECTIVE: The aim of this investigation was to evaluate the usefulness of a dual
      isotope SPECT technique to assess simultaneously striatal dopamine binding
      structures - presynaptic dopamine transporter (DAT) and postsynaptic dopamine
      D(2) receptor - in first-episode, drug-naive schizophrenic patients compared to
      healthy control persons. Additionally, relations between radioligand binding to
      DAT and D(2) and positive symptoms were assessed. METHODS: Twenty acutely ill
      inpatients suffering from a first acute schizophrenic episode and 12 healthy
      control persons participated in the study. Patients were naive with respect to
      neuroleptic or antidepressant medication. A dual-isotope SPECT protocol was
      performed using combined application of [99mTc]TRODAT-1 and [123I]IBZM. On the
      day of SPECT, psychopathology was assessed in the patient group by PANSS rating.
      RESULTS: In the patient but not in the healthy control group there was a
      significant correlation between DAT and D(2) receptor availability. Patients with
      predominant positive symptoms (n=12) had a significantly higher DAT availability
      compared to the healthy control group. An inverse correlation between DAT and
      D(2) availability and the extent of "delusions", "conceptual disorganization",
      and "hallucinatory behaviour" could be demonstrated. DISCUSSION: The data
      obtained with this dual-isotope SPECT technique show a change in interaction
      between striatal DAT and D(2) receptor in first-episode, never-treated
      schizophrenic patients. Additionally, an association between dopamine
      transmission and the core symptoms of the acute psychotic syndrome was found.

PMID- 18083346
TI  - HSP105 interacts with GRP78 and GSK3 and promotes ER stress-induced caspase-3
      activation.
AB  - Stress of the endoplasmic reticulum (ER stress) is caused by the accumulation of
      misfolded proteins, which occurs in many neurodegenerative diseases. ER stress
      can lead to adaptive responses or apoptosis, both of which follow activation of
      the unfolded protein response (UPR). Heat shock proteins (HSP) support the
      folding and function of many proteins, and are important components of the ER
      stress response, but little is known about the role of one of the major large
      HSPs, HSP105. We identified several new partners of HSP105, including glycogen
      synthase kinase-3 (GSK3), a promoter of ER stress-induced apoptosis, and GRP78, a
      key component of the UPR. Knockdown of HSP105 did not alter UPR signaling after
      ER stress, but blocked caspase-3 activation after ER stress. In contrast, caspase
      3 activation induced by genotoxic stress was unaffected by knockdown of HSP105,
      suggesting ER stress-specificity in the apoptotic action of HSP105. However,
      knockdown of HSP105 did not alter cell survival after ER stress, but instead
      diverted signaling to a caspase-3-independent cell death pathway, indicating that
      HSP105 is necessary for apoptotic signaling after UPR activation by ER stress.
      Thus, HSP105 appears to chaperone the responses to ER stress through its
      interactions with GRP78 and GSK3, and without HSP105 cell death following ER
      stress proceeds by a non-caspase-3-dependent process.

PMID- 18083349
TI  - Cognitive deficits in early-onset schizophrenia spectrum patients and their non
      psychotic siblings: a comparison with ADHD.
AB  - BACKGROUND: Previous research has shown cognitive deficits in patients with
      schizophrenia spectrum disorders in the areas of executive function, verbal
      memory and attention. Subtle deficits have been shown in healthy first-degree
      relatives of patients, suggesting that they may be trait markers. The specificity
      of these markers for schizophrenia compared with another neurodevelopmental
      disorder, Attention Deficit Hyperactivity Disorder (ADHD) has not been reliably
      established. METHODS: The Rey Auditory Verbal Learning Test (RAVLT), Hayling
      Sentence Completion Test (HSCT), FAS Test of orthographic verbal fluency (FAS)
      and Continuous Performance Test-Identical Pairs (CPT-IP) were administered to
      adolescent schizophrenia spectrum patients (SZ; n=30), adolescent siblings of
      schizophrenia spectrum patients (SZ-SIB; n=36), healthy control participants (HC;
      n=72); a neurodevelopmental comparison group of adolescents with ADHD (n=27).
      RESULTS: The SZ group were impaired on all measures. The SZ-SIB group were
      impaired on IQ, immediate recall (RAVLT), target sensitivity (CPT-IP), response
      initiation (HSCT); error rates for the FAS and HSCT. There were no significant
      differences between the SZ-SIB and ADHD groups on individual measures of
      cognitive function. Principal Components Analysis revealed four factors on which
      further analyses were conducted. The SZ-SIB and ADHD groups showed different
      profiles of impairment on components related to response initiation and sustained
      attention/vigilance when each was compared with the HC group. CONCLUSIONS:
      Deficits in intellectual function, verbal memory and response
      initiation/inhibition were found in the SZ-SIB group indicating that these are
      markers of risk for schizophrenia. Subtle differences in profiles of impairment
      in the SZ-SIB and ADHD groups on composite measures of attention and response
      initiation require further investigation.

PMID- 18083351
TI  - Immobilization of cationic rifampicin-loaded liposomes on polystyrene for drug
      delivery applications.
AB  - Polymer-associated infections are a major problem in implanted or intravascular
      devices. Among others, microorganisms of the staphylococcal family have been
      identified as the most important culprit. Prevention of bacterial adhesion and
      colonization of polymeric surfaces by release of antimicrobial agents
      incorporated into the polymers itself are currently under study. We have
      developed a novel method for the functionalization of a polymeric surface which
      is based on the deposition of covalently coupled lipid structures from antibiotic
      loaded vesicles. We have found that such process significantly reduces the
      bacterial growth on polystyrene material. In this work, lipid coverage obtained
      from multilamellar (MLVs) and extruded unilamellar (LUVs) vesicles were analyzed
      with respect to their adhesion efficiency on three types of polystyrene (PS) well
      plates. Two methods of lipid deposition were characterized and compared in terms
      of surface lipid density and time stability: deposition of cationic vesicles on
      negatively charged surfaces and formation of covalent linkages between
      functionalized lipids and amines enriched surfaces. In order to study the
      antibiotic encapsulation efficiency we measured how the rifampicin (RIF) loading
      was affected by changes of liposome charge upon introduction of various amounts
      of stearylamine (SA), distearoyl-trimethylammonium propane (DSTAP) or
      dioleoyloxypropyl-trimethylammonium chloride (DOTAP) into the liposomal
      formulation. RIF-coated polymeric surfaces were also tested against a
      Staphylococcus epidermidis strain to evaluate their efficacy in vitro, showing
      that only approximately 2% of such bacteria inoculated on MLV-treated PS
      substrate were able to proliferate. Covalently immobilized lipid films showed
      about a tenfold increase in time stability compared to electrostatically bonded
      lipid films. Furthermore, substrates covalently modified with RIF-loaded MLVs
      retained an antibacterial activity for up to 12 days when aged in buffer at 37
      degrees C. Such antimicrobial polymer coatings show promise for their use as
      antibacterial barrier for the prevention of catheter-related infections.

PMID- 18083350
TI  - Transcription factor broad suppresses precocious development of adult structures
      during larval-pupal metamorphosis in the red flour beetle, Tribolium castaneum.
AB  - Broad (br), a transcription factor containing the Broad-Tramtrack-Bric-a-brac
      (BTB) and zinc finger domains was shown to mediate 20-hydroxyecdysone (20E)
      action and pupal development in Drosophila melanogaster and Manduca sexta. We
      determined the key roles of br during larval-pupal metamorphosis using RNA
      interference (RNAi) in a coleopteran insect, Tribolium castaneum. Two major peaks
      of T. castaneum broad (Tcbr) mRNA, one peak at the end of feeding stage prior to
      the larvae entering the quiescent stage and another peak during the quiescent
      stage were detected in the whole body and midgut tissue dissected from staged
      insects. Expression of br during the final instar larval stage is essential for
      successful larval-pupal metamorphosis, because, RNAi-mediated knock-down of Tcbr
      during this stage derailed larval-pupal metamorphosis and produced insects that
      showed larval, pupal and adult structures. Tcbr dsRNA injected into the final
      instar larvae caused reduction in the mRNA levels of genes known to be involved
      in 20E action (EcRA, E74 and E75B). Tcbr dsRNA injected into the final instar
      larvae also caused an increase in the mRNA levels of JH-response genes (JHE and
      Kr-h1b). Knock-down of Tcbr expression also affected 20E-mediated remodeling of
      midgut during larval-pupal metamorphosis. These data suggest that the expression
      of Tcbr during the final instar larval stage promotes pupal program while
      suppressing the larval and adult programs ensuring a transitory pupal stage in
      holometabolous insects.

PMID- 18083352
TI  - Investigation on the relationship between leaf water use efficiency and physio
      biochemical traits of winter wheat under rained condition.
AB  - Different statistical methods and path analysis were used to study the
      relationship between leaf water use efficiency (WUE) and physio-biochemical
      traits for 19 wheat genotypes, including photosynthesis rate (P(n)), stomatal
      conductance (g(s)), transpiration rate (T(r)), intercellular concentration of
      carbon oxide (C(i)), leaf water potential (Psi(w)), leaf temperature, wax
      content, leaf relative water content (RWC), rate of water loss from excised-leaf
      (RWL), peroxidase (POD) and superoxide dismutase (SOD) activities. The results
      showed that photosynthesis rate, stomatal conductance and transpiration rate were
      the most important leaf WUE variables under rained conditions. Based on the
      results of five statistical analyses, it is reasonable to assume that high leaf
      WUE wheat under the rained could be obtained by selecting breeding materials with
      high photosynthesis rate, low transpiration rate and stomatal conductance.

PMID- 18083353
TI  - Comparison of two types of population pharmacokinetic model structures of
      paclitaxel.
AB  - Two main types of model structures have been proposed for the pharmacokinetics of
      paclitaxel; an empirical model structure based on total plasma concentrations of
      paclitaxel, and a mechanism-based model structure derived from both total and
      unbound paclitaxel concentrations and concentrations of the formulation vehicle
      Cremophor EL. The purpose was to compare the two pharmacokinetic model structures
      when only total paclitaxel concentrations are available. To support the mechanism
      based model structure with Cremophor EL concentrations, in silico concentrations
      were obtained from simulations of a pharmacokinetic model available in the
      literature. Local algebraic observability was tested on both model structures;
      the mechanism-based model structure was found, with high probability, not to be
      algebraically observable if total paclitaxel concentration is considered to be
      the only model output, and if no kind of prior information is used. Sensitivity
      analysis was performed to reveal which parameter should be fixed in order to make
      it locally observable. Parameter estimation was then performed on both model
      structures using nonlinear mixed effects and data from a clinical study. The
      estimated mechanism-based model turned out to have a somewhat better fit to data
      than the corresponding empirical model, delta AIC=-31, where AIC is the Akaike
      Information Criterion. Hold-out validation was performed on three patients, but
      did not favour any of the models. In conclusion, since the mechanism-based model
      structure behaved at least as good as the empirical model structure, it is
      suggested that the former model structure should be used since it offers a more
      accurate description of the disposition.

PMID- 18083354
TI  - Vinorelbine and infusional 5-fluorouracil in anthracycline and taxane pre-treated
      metastatic breast cancer.
AB  - AIMS: To evaluate the efficacy and toxicity of a combination of intravenous
      vinorelbine and 5-fluorouracil (5-FU) given by continuous infusion in the
      treatment of metastatic breast cancer previously treated with anthracyclines and
      taxanes. MATERIALS AND METHODS: Sixty-one patients with metastatic breast cancer
      were treated with intravenous vinorelbine 30 mg/m2 on days 1 and 8 of each 21-day
      cycle together with 5-FU 200 mg/m2/day by continuous infusion. All had previously
      been treated with an anthracycline and 41% had also been previously treated with
      a taxane. All had normal haematological, renal and hepatic function and all but
      three had an Eastern Cooperative Oncology Group performance score of 2 or better.
      RESULTS: The overall response rate by World Health Organization criteria was 46%
      (28 patients); excluding nine non-evaluable patients gave a response rate of 54%.
      In patients who had previously been treated with both an anthracycline and a
      taxane, a response rate of 50% was observed (12 of 24 patients). Severe toxicity
      was uncommon, as was toxicity attributable to infusional 5-FU. Myelosuppression
      was rarely severe, but was common and led to delay or dose reduction in 38% of
      treatments. Eleven patients (18%) were admitted with fever and/or neutropenia and
      one patient died. The median received dose intensity was vinorelbine 16
      mg/m2/week and 5-FU 143 mg/m2/day. CONCLUSIONS: The combination of vinorelbine
      and infusional 5-FU is active in metastatic breast cancer, including in patients
      previously treated with an anthracycline and a taxane. Toxicity is generally
      manageable, but myelosuppression is significant at this dose regimen. Recommended
      doses for routine clinical use are 5-FU 200 mg/m2/day and intravenous vinorelbine
      30 mg/m2 days 1 and 15 on a 28-day cycle.

PMID- 18083355
TI  - Effects of short-term low- and high-carbohydrate diets on postprandial metabolism
      in non-diabetic and diabetic subjects.
AB  - BACKGROUND AND AIM: Low-fat high-carbohydrate diets raise plasma triacylglycerol
      (TG) concentrations. To test whether the nature of the carbohydrate affects
      metabolic responses, we conducted a randomized cross-over study using a short
      term, intensive dietary modification. METHODS AND RESULTS: Eight non-diabetic
      subjects and four subjects with diet-controlled type 2 diabetes participated.
      They followed three isoenergetic diets, each for 3 days: high-fat (50% energy
      from fat), high-starch and high-sugar (each 70% energy from carbohydrate). Normal
      foods were provided. We measured plasma TG and glucose concentrations, fasting
      and after a standard test meal, on day 4 following each dietary period. Fasting
      TG concentrations were greatest following the high-sugar diet (mean+/-SEM for all
      subjects 1900+/-420micromol/l) and lowest following high-fat (1010+/
      130micromol/l) (P=0.001); high-starch (mean 1500+/-310) and high-fat did not
      differ significantly (P=0.06). There was a greater effect in the diabetic
      subjects (diet x diabetes status interaction, P=0.008). Postprandial TG
      concentrations were similarly affected by prior diet (P<0.001) with each diet
      different from the others (P<or=0.01). The elevation of fasting TG on the high
      sugar versus high-fat diet was strongly related to the average fasting TG
      concentration (P=0.01 across both diabetic and non-diabetic subjects). Fasting
      glucose concentrations were not affected by prior diet but postprandial glucose
      concentrations were (P=0.018), with significantly higher values after the high
      fat than the high-sugar diet (P=0.03). CONCLUSIONS: The short-term TG-raising
      effect of a very low-fat diet is dependent upon the nature of the carbohydrate,
      with a greater effect of a sugar-rich than a complex-carbohydrate-rich diet.

PMID- 18083356
TI  - Central adiposity and left ventricular mass in obese children.
AB  - AIM: The impact of central adiposity on left ventricular (LV) mass in childhood
      obesity has been little explored. This study evaluates whether central obesity
      influences LV mass and function in obese children. METHODS AND RESULTS:
      Biochemical, anthropometric and echocardiographic measurements were taken in
      obese (n=111, mean age 10.6+/-2.5 years) and non-obese children (n=30, mean age
      10.8+/-3.0 years). Left ventricular function was analyzed by conventional and
      tissue Doppler echocardiography. LV mass was calculated according to the Penn
      convention and indexed for height(2.7) (LVM(i)). The obese group showed increased
      levels of LVM(i) as compared to the non-obese group (35.7+/-8.5 vs 23.5+/-2.8
      g/h(2.7), p<0.0001). Among obese children, we observed a significant increase of
      LVM(i) across tertile of waist-height ratio (WHtR). The subjects identified by
      the highest tertile of WHtR, as compared to subjects identified by the lowest
      tertile, showed higher levels of BMI (29.5+/-5.4 vs 31.0+/-5.0 kg/m(2), p<0.0001)
      and LVM(i) (32.1+/-6.5 vs 37.1+/-8.5 g/h(2.7), p<0.01). Among obese children a
      positive correlation (standardized for age and gender) was found between LVM(i)
      and BMI (r=0.282, p<0.01) and WHtR (r=0.334, p<0.0001). To analyze the
      independent predictors of LVM(i), a stepwise linear regression analysis was
      performed using age, gender, BMI, blood pressure, heart rate, HOMA-IR and WHtR as
      independent variables. LVM(i) was independently associated only with WHtR
      (beta=0.309, t=3.238, p=0.002). CONCLUSION: Obese children show an increased
      LVM(i) and a preserved LV function. Central adiposity is the major determinant of
      left ventricular mass.

PMID- 18083357
TI  - Epicardial fat thickness: relationship with plasma visfatin and plasminogen
      activator inhibitor-1 levels in visceral obesity.
AB  - BACKGROUND AND AIM: Epicardial fat (EF), a true visceral adipose tissue (VAT)
      deposited around the heart, is considered as possible cardiovascular risk
      indicator, in view of its ability to produce and release several inflammatory
      adipo-cytokines. It is still not known whether increased cardiac adiposity is
      related to increased inflammatory adipo-cytokines in obesity. The aim of this
      study was to evaluate whether echocardiographic EF thickness, an indicator of
      cardiac adiposity, is related to circulating levels of inflammatory adipo
      cytokines such as visfatin and plasminogen activator inhibitor-1 (PAI-1) in
      visceral obesity. METHODS AND RESULTS: EF thickness (measured by
      echocardiography), visfatin, PAI-1 antigen and some inflammatory markers were
      studied in 42 women, 27 of them severely obese (OB) (BMI 43.5+/-4.8 kg/m(2)) but
      with no apparent complications, and 15 normal-weight controls. Abdominal VAT in
      the OB was assessed by computed tomography. OB had thicker EF and higher visfatin
      and PAI-1 antigen concentrations than controls (P<0.0001). EF thickness, log
      visfatin and log-PAI-1 antigen concentrations directly correlated with VAT
      (P<0.0001). Log-visfatin and log-PAI-1 antigen were correlated with EF thickness
      even after adjusting for indices of fat distribution (P<0.01 and P<0.001
      respectively). Moreover, when dividing OB on the basis of median EF thickness,
      women with greater EF thickness had more VAT and higher adipo-cytokine
      concentrations and inflammatory markers. CONCLUSIONS: This study suggests that EF
      thickness, an indicator of cardiac adiposity, may be significantly related to
      inflammatory adipo-cytokines in visceral-obese patients. This suggests EF might
      be used as an easy and reliable marker of visceral adiposity and inflammation and
      as a cardiovascular risk indicator.

PMID- 18083358
TI  - Hyaluronidase activity is modulated by complexing with various polyelectrolytes
      including hyaluronan.
AB  - Hyaluronidase (HAase) plays an important role in the control of the size and
      concentration of hyaluronan (HA) chains, whose biological properties strongly
      depend on their length. Our previous studies of HA hydrolysis catalyzed by
      testicular HAase demonstrated that, whilst the substrate-dependence curve has a
      Michaelis-Menten shape with a 0.15 mol L(-1) ionic strength, at low ionic
      strength (5 mmol L(-1)), a strong decrease in the initial hydrolysis rate is
      observed at high substrate concentrations; the HA concentration for which the
      initial rate is maximum increases when the HAase concentration is increased.
      After examination of various hypotheses, we suggested that this could be
      explained by the ability of HA to form non-specific complexes with HAase, which
      thus becomes unable to catalyze HA hydrolysis. In order to verify this
      hypothesis, we first showed from turbidimetric measurements that HAase, like
      albumin, is able to form electrostatic complexes with HA. Albumin then was used
      as a non-catalytic protein able to compete with HAase for the formation of non
      specific complexes with HA, allowing HAase to be free and catalytically active.
      The kinetic results showed that the HA-HAase non-specific complex inhibits HAase
      catalytic activity towards HA. Depending on the albumin concentration with
      respect to the HAase and HA concentrations, albumin can either remove this
      inhibition or induce another type of inhibition. Finally, the extent of such non
      specific interactions between polyelectrolytes and proteins in HAase inhibition
      or activation, in particular under in vivo conditions, is discussed.

PMID- 18083360
TI  - Asymmetric focal adhesion disassembly in motile cells.
AB  - Cell migration requires the integration and coordination of specific focal
      adhesion dynamics at the cell front, center and rear. In this review, we will
      present our understanding of the regulation of adhesion turnover and disassembly
      in various regions of the cell. Adhesion turnover involves a number of tyrosine
      kinases and phosphatases, most of which are engaged in FAK signaling pathways.
      Additionally, adhesions are regulated by tensile forces that depend on dynamic
      coupling with the actin cytoskeleton. The distribution of adhesion disassembly
      throughout a motile cell is likely coordinated by the asymmetry of the
      microtubule network. We present a model that suggests two stages of microtubule
      driven adhesion disassembly: destabilization and detachment.

PMID- 18083359
TI  - Preferential enrichment of liver phospholipids in docosahexaenoate relative to
      eicosapentaenoate in omega-3-depleted rats injected with a medium-chain
      triglyceride: fish oil emulsion.
AB  - The bolus intravenous injection of a novel medium-chain triglyceride:fish oil
      (FO) emulsion was recently proposed as a tool to provoke a rapid enrichment of
      cell phospholipids in long-chain polyunsaturated omega-3 fatty acids. In the
      present study, the enrichment of liver phospholipids and triglycerides in
      C20:5omega-3, C22:5omega-3 and C22:6omega-3 was assessed 60min after the
      intravenous administration of FO (1.0ml) to second-generation omega-3-depleted
      rats. When compared to uninjected rats, or animals injected with a control omega
      3 fatty acid-poor medium-chain triglyceride:olive oil (OO) emulsion, the
      enrichment of liver phospholipids, and to a lesser extent liver triglycerides,
      attributable to the injection of the FO emulsion was more pronounced for
      C22:6omega-3 than C20:5omega-3, despite the presence of equal amounts of these
      two omega-3 fatty acids in the injected diglycerides and triglycerides. The
      possible determinants and potential beneficial effects of such a difference are
      briefly discussed.

PMID- 18083361
TI  - Adsorption of SO2 and NO from incineration flue gas onto activated carbon fibers.
AB  - Activated carbon fibers (ACFs) were used to remove SO2 and NO from incineration
      flue gas. Three types of ACFs in their origin state and after pretreatment with
      HNO3, NaOH, and KOH were investigated. The removal efficiencies of SO2 and NO
      were determined experimentally at defined SO2 and NO concentrations and at
      temperatures of 150, 200 and 260 degrees C. Experimental results indicated that
      the removal efficiencies of SO2 and NO using the original ACFs were < 56% and <
      27%, respectively. All ACFs modified with HNO3, NaOH, and KOH solution could
      increase the removal efficiencies of SO(2) and NO. The mesopore volumes and
      functional groups of ACFs are important in determining the removal of SO2 and NO.
      When the mesopore volumes of the ACFs are insufficient for removing SO2 and NO,
      the functional groups on the ACFs are not important in determining the removal of
      SO2 and NO. On the contrary, the effects of the functional groups on the removal
      of SO2 and NO are more important than the mesopore volumes as the amount of
      mesopores on the ACFs is sufficient to remove SO2 and NO. Moreover, the removal
      efficiencies of SO2 and NO were greatest at 200 degrees C. When the inlet
      concentration of SO2 increased to 600 ppm, the removal efficiency of SO2
      increased slightly and the removal efficiency of NO decreased.

PMID- 18083362
TI  - Quantifying the transport impacts of domestic waste collection strategies.
AB  - This paper models the effects of three different options for domestic waste
      collection using data from three Hampshire authorities: (i) joint working between
      neighbouring waste collection authorities; (ii) basing vehicles at waste disposal
      sites; and (iii) alternate weekly collection of residual waste and dry
      recyclables. A vehicle mileage savings of 3% was modelled for joint working,
      where existing vehicle allocations to depots were maintained, which increased to
      5.9% when vehicles were re-allocated to depots optimally. Vehicle mileage was
      reduced by 13.5% when the collection rounds were based out of the two waste
      disposal sites rather than out of the existing depots, suggesting that the former
      could be the most effective place to keep vehicles providing that travel
      arrangements for the crews could be made. Alternate weekly collection was
      modelled to reduce vehicle mileage by around 8% and time taken by 14%, when
      compared with a typical scenario of weekly collection of residual and fortnightly
      collection of recyclable waste. These results were based on an assumption that
      20% of the residual waste would be directly diverted into the dry recyclables
      waste stream.

PMID- 18083363
TI  - Carbon nanofiber-based composites for the construction of mediator-free
      biosensors.
AB  - Carbon nanofibers (CNFs), with typical diameters of approximately 80 nm and
      lengths of the order of micrometers, are extremely attractive in bioanalytical
      area as they can combine properties of high surface area, non-toxicity,
      acceptable biocompatibility, ease of fabrication, chemical and electrochemical
      stability, good electrical conductivity. In this work, CNF-based composites were
      successfully used as an immobilization matrix for the construction of a
      reagentless mediator-free hemoglobin-based H2O2 biosensor. The results revealed
      that hemoglobin retained its essential secondary structure in the CNF-based
      composite film. With the advantages of organic-inorganic hybrid materials,
      dramatically facilitated direct electron transfer of hemoglobin and good
      bioelectrocatalytic activity towards H2O2 were demonstrated. The biosensor
      displayed good performance along with good long-term stability. The CNF-based
      composites were proved to be a promising biosensing platform for the construction
      of mediator-free biosensors, and may find wide potential applications in
      biosensors, biocatalysis, bioelectronics and biofuel cell.

PMID- 18083365
TI  - NMR structural studies on membrane proteins.

PMID- 18083364
TI  - Expert consensus document on the treatment of descending thoracic aortic disease
      using endovascular stent-grafts.
AB  - Between 43,000 and 47,000 people die annually in the United States from diseases
      of the aorta and its branches and continues to increase. For the thoracic aorta,
      these diseases are increasingly treated by stent-grafting. No prospective
      randomized study exists comparing stent-grafting and open surgical treatment,
      including for disease subgroups. Currently, one stent-graft device is approved by
      the Food and Drug Administration for descending thoracic aortic aneurysms
      although two new devices are expected to obtain FDA approval in 2008. Stent-graft
      devices are used "off label" or under physician Investigational Device Exemption
      studies for other indications such as traumatic rupture of the aorta and aortic
      dissection. Early first-generation devices suffered from problems such as stroke
      with insertion, ascending aortic dissection or aortic penetration from struts,
      vascular injury, graft collapse, endovascular leaks, graft material failure,
      continued aneurysm expansion or rupture, and migration or kinking; however, the
      newer iterations coming to market have been considerably improved. Although the
      devices have been tested in pulse duplicators out to 10 years, long-term
      durability is not known, particularly in young patients. The long-term
      consequences of repeated computed tomography scans for checking device integrity
      and positioning on the risk of irradiation-induced cancer remains of concern in
      young patients. This document (1) reviews the natural history of aortic disease,
      indications for repair, outcomes after conventional open surgery, currently
      available devices, and insights from outcomes of randomized studies using stent
      grafts for abdominal aortic aneurysm surgery, the latter having been treated for
      a longer time by stent-grafts; and (2) offers suggestions for treatment.

PMID- 18083367
TI  - Melanoma 2007: current state and preview of the future.

PMID- 18083369
TI  - Melanoma: prevention and early detection.
AB  - Exposure to ultraviolet radiation is the main modifiable risk factor for
      melanoma. Strong epidemiologic and molecular evidence links sun exposure to the
      development of melanoma. Given the ubiquitous abundance of ultraviolet radiation,
      prevention aimed at blocking sun exposure is recommended by the American Academy
      of Dermatology, the Skin Cancer Foundation, the American Cancer Society, the
      Centers for Disease Control, and the Environmental Protection Agency. However, in
      contrast to other forms of skin damage, controversial data regarding sunscreen
      use and increased melanoma risk, possibly secondary to more overall sun exposure
      in melanoma patients, requires clarification. Primary care physicians may not be
      as adept at identifying worrisome lesions, but they have more opportunity to make
      the diagnosis. False positive identification of lesions and biopsy does not lead
      to extreme morbidity. Counseling patients to perform self skin examinations also
      contributes to important early detection.

PMID- 18083368
TI  - Genetics: what advice for patients who present with a family history of melanoma?
AB  - A significantly increased susceptibility to melanoma may manifest as a family
      history of melanoma (plus or minus pancreatic cancer), the development of
      multiple primary tumors, or melanoma in the context of numerous and clinically
      atypical moles (the atypical mole syndrome). In families, increased
      susceptibility may occur as a result of the inheritance of mutations at the
      CDKN2A locus or in the CDK4 gene. We describe what is known about these genes and
      discuss the implications for genetic counseling and gene testing. Lower levels of
      risk are associated with genetically determined pigmentary variation within
      populations. This variation is attributable to inheritance of variants in the
      MC1R gene and putatively other genes such as OCA2, which is discussed. Melanoma
      is causally related to sun exposure in the majority of patients, although the
      patterns of sun exposure, which are most important, remain controversial. The
      role of risk estimation for individuals in giving advice about sun exposure is
      considered.

PMID- 18083370
TI  - Failure of senescence in the dysplasia-melanoma sequence: demonstration using a
      tissue microarray and a revised paradigm for melanoma.
AB  - In order to correlate changes in morphology to changes in molecular attributes,
      we constructed a tissue microarray of thin and thick melanomas selected to
      represent progression from dysplasia to early and advanced melanoma. Hematoxylin
      and eosin (H&E) staining and immunohistology with antibodies to cyclin D1, p16,
      Ki67, and Bcl-2 were performed. Observations were interpreted using a revised
      paradigm for the dysplasia-melanoma sequence in which the early steps of
      melanomatous growth develop in an accretive fashion similar to the growth of the
      common acquired nevus. The co-expression of cyclin D1 and p16 persisted from
      dysplasia to early melanomatous vertical growth. Malignant transformation
      characterized by absence of p16 and presence of increased cyclin D1 and increased
      Ki67 and confirmed by clinically documented metastasis occurred during the
      process of evolving melanomatous vertical growth. The interplay of mutated BRAF,
      cyclin D1, and p16 with anti-apoptosis and failure of senescence may account for
      the existence of nevi and dysplastic nevi and for their relationship to melanoma,
      and may indirectly account for the infrequency of nevi in the lentiginous
      melanomas that lack mutated BRAF. These observations suggest a need for more
      detailed study of transformation to malignancy in the various subsets of
      melanoma.

PMID- 18083371
TI  - The molecular basis of melanomagenesis and the metastatic phenotype.
AB  - The last two decades have seen spectacular advances in our understanding of the
      biology of melanoma and, in particular, have elucidated the mechanisms operative
      in disease initiation and progression. With respect to the former, the genetics
      of melanoma and in particular the impact of genetic defects on dysregulation of
      the cell cycle are key issues in malignant transformation and are a major focus
      of this review. With respect to the latter, consideration also is given to the
      acquisition of growth factor autonomy and the capacity for invasion and
      metastasis from the standpoint of cell adhesion, motility, and matrix digestion.
      These events have specific morphologic correlates that will be briefly addressed.
      Where relevant, we will address certain of the modern pharmacogenetic strategies
      that flow from these novel observations concerning melanoma biology.

PMID- 18083372
TI  - Reflecting on the 2001 American Joint Committee on Cancer Staging System for
      melanoma.
AB  - The Melanoma Staging Committee of the American Joint Committee on Cancer (AJCC)
      promulgated in 2001 major revisions of the melanoma tumor-node-metastasis (TNM)
      categories and stage grouping criteria, for a new staging system of cutaneous
      melanoma. The Committee invited data analyses relevant to the proposed new
      melanoma staging for validation of the system. Validation studies that were
      published subsequently confirmed most of the parameters of the new staging
      system, identified new prognostic factors that had not been included in the
      revised AJCC staging, whereas the prognostic power of some parameters could not
      be confirmed in the data of other institutions. This article provides an in-depth
      analysis of the current AJCC staging for melanoma, addresses areas of
      controversy, and offers proposals for consideration at the next revision of the
      system.

PMID- 18083374
TI  - Randomized adjuvant therapy trials in melanoma: surgical and systemic.
AB  - The utility of adjuvant surgical procedures in the management of primary
      melanomas has been evaluated in a large number of phase III randomized trials.
      These trials have shown that wide margins, elective lymph node dissection,
      sentinel lymph node (SLN) biopsy, and prophylactic isolated limb perfusion (ILP)
      do not improve survival but may improve locoregional control. Based on the claim
      of providing a survival benefit, these surgical procedures cannot be considered
      standard of care in the routine management of primary melanoma. Regarding the
      role of SLN biopsy it must be stated that this procedure provides the best
      information on prognosis and provides us with an important tool to stratify for
      and study more homogeneous patient populations to evaluate adjuvant systemic
      therapies in randomized phase III trials. The utility of systemic adjuvant
      therapy remains marginal as a result of the fact that a lack of effective drugs
      in stage IV disease is reflected by a lack of effective adjuvant therapies in
      stage II-III melanoma. Thus far, chemotherapeutic drugs, immunostimulants, and
      various vaccines have all failed. Interferon (IFN) has an effect on relapse-free
      survival but not on overall survival. Thus its impact is judged by many to be too
      small to be considered standard of care. The population of patients that can
      benefit from IFN needs to be better defined by identifying new biomarkers by
      genomic and proteomic studies, which are ongoing.

PMID- 18083375
TI  - Melanoma vaccines.
AB  - There has been a long fascination with immunizing against cancer in general and
      against melanoma in particular. The earliest melanoma vaccines were formulated
      from autologous or allogeneic melanoma cells. Subsequently, molecularly defined
      vaccines made from proteins, peptides, or gangliosides were developed and,
      recently, DNA-based vaccines are currently being tested. Randomized trials using
      allogeneic melanoma cells/lysates or gangliosides have not demonstrated a
      clinical benefit, although in some trials, clinical benefit was seen in large
      subsets. On the other hand, some clinical trials indicated that vaccine therapy
      could be associated with a poorer survival. There are several mechanisms now
      identified by which melanoma cells can avoid detection by T cells, such as loss
      of expression of antigen or human leukocyte antigen (HLA) molecules, and tumor
      vascular adhesion molecules. Also, mediators of immune tolerance are now well
      characterized such as regulatory T cells and inhibitory cytokines secreted by
      melanoma cells. Future approaches for immunizing against melanoma will have to
      incorporate strategies to overcome these barriers. Strategies being tested
      include depletion of regulatory T cells, immunization in the setting of
      lymphopenia, and blockade of T-cell inhibitory molecules such as CTLA-4. Once a
      relevant clinical response can be induced, it should be possible to develop
      validated immunoassays that will direct future melanoma vaccine development.

PMID- 18083373
TI  - Surgery and sentinel lymph node biopsy.
AB  - In patients with melanoma, surgery is pivotal not only for the primary tumor but
      also for regional and often distant metastases. The minimally invasive technique
      of sentinel node (SN) biopsy has become standard for detection of occult regional
      node metastasis in patients with intermediate-thickness primary melanoma; in
      these patients it has a central role in determining prognosis and a significant
      impact on survival when biopsy results are positive. Its role in thin melanoma
      remains under evaluation. The regional tumor-draining SN also is a useful model
      for studies of melanoma-induced immunosuppression. Although completion
      lymphadenectomy remains the standard of care for patients with SN metastasis,
      results of ongoing phase III trials will indicate whether SN biopsy without
      further lymph node surgery is adequate therapy for certain patients with minimal
      regional node disease.

PMID- 18083377
TI  - Management of metastatic melanoma.
AB  - Since the original approval of dacarbazine for the treatment of metastatic
      malignant melanoma, considerable effort has been expended in attempts to improve
      survival. This end point is the most unequivocal and ultimately meaningful for
      patients with cancer but has been one upon which clinical trials conducted to
      date have failed to demonstrate a meaningful impact. Little data regarding
      quality of life are currently available, but outside the setting of a clinical
      trial, a convenient single-agent dose regimen of dacarbazine is probably the best
      approach, currently. Targeted agents that are designed to abrogate various
      pathways implicated in signal transduction, cell cycle checkpoints,
      immunomodulation, and DNA repair offer promising novel approaches for the
      treatment of metastatic melanoma. However, cytotoxics may be essential backbones
      for combinations with these molecules. Phase II designs with targeted agents may
      require new and innovative end points to identify activity. The rational use of
      agents capable of abrogating drug resistance offers other opportunities for
      systemic chemotherapy that may then give rise to more rationally developed
      combinations.

PMID- 18083376
TI  - Adoptive cell transfer therapy.
AB  - Adoptive cell transfer therapy has developed into a potent and effective
      treatment for patients with metastatic melanoma. Current application of this
      therapy relies on the ex vivo generation of highly active, highly avid tumor
      reactive lymphocyte cultures from endogenous tumor infiltrating lymphocytes or on
      the genetic engineering of cells using antigen receptor genes to express de novo
      tumor antigen recognition. When autologous anti-tumor lymphocyte cultures are
      administered to patients with high-dose interleukin (IL)-2 following a
      lymphodepleting conditioning regimen, the cells can expand in vivo, traffic to
      tumor, and mediate tumor regression and durable objective clinical responses.
      Current investigation seeks to improve the methods for generating and
      administering the lymphocyte cultures, and future clinical trials aim to improve
      durable response rates and extend the patient populations that are candidates for
      treatment.

PMID- 18083378
TI  - The RTK/RAS/BRAF/PI3K pathways in melanoma: biology, small molecule inhibitors,
      and potential applications.
AB  - The discovery of mutations in the BRAF signaling molecule in a large proportion
      of cutaneous melanomas immediately suggested the prospect of effective therapies
      for this disease. The most appealing initial target has been BRAF itself, as most
      mutations involve a single residue in the kinase domain of the protein. But the
      identification of the high mutation rate in this signaling intermediate also
      suggests that other molecules up- and downstream of BRAF might be productively
      targeted. Indeed, several receptor tyrosine kinases, as well as RAS, are mutated
      in a small number of melanoma cases. Moreover, genetic alterations in the
      phosphotidylinositol-3-kinase (PI3K) pathway, especially in PTEN, suggest that
      this route also poses opportunities for therapeutic exploitation. We will review
      here the genetic evidence suggesting the utility of targets on these pathways. We
      will also summarize the recent clinical data that have accumulated from initial
      trials designed to test BRAF inhibition and targeting of other molecules.
      Finally, we provide an overview of molecules entering the clinic and soon to be
      tested in clinical studies, as well as strategies for their employment as
      monotherapy and in combinations.

PMID- 18083380
TI  - Roadmap for new opportunities in melanoma research.
AB  - Investigators representing all major melanoma research areas present an overview
      of the most important challenges for the field. Four major research areas are
      covered plus the training of new investigators. For each area we first describe
      the present status, its strengths and weaknesses, and then outline specific
      recommendations. In basic research of melanoma, we outline the pertinent issues
      for melanoma classification, understanding melanocyte development and
      transformation, melanoma resistance, tumor microenvironment, metastasis, animal
      models, immune response, and blood and tissue diagnostics. In clinical research
      we provide an overview of the current challenges and the strategies for
      characterization, monitoring, and therapy. It will be important to develop strong
      research and clinical infrastructures by establishing tumor banks, identifying
      and validating biomarkers, developing new imaging techniques, and increasing
      multidisciplinary collaboration and communication. To strengthen the field we
      need to recruit both young and established investigators and foster career
      development plans that cover all disciplines. Recent research advances provide
      significant opportunities to have a major impact on this devastating disease.
      This group provides recommendations for both short- and long-term strategies that
      build on research strengths and opportunities established by the many members of
      the research community.

PMID- 18083379
TI  - Angiogenesis in melanoma.
AB  - The process of angiogenesis is crucial for progression and metastasis of the
      majority of solid tumors including melanomas. The current review summarizes
      existing knowledge of the mechanisms of angiogenesis in melanoma, as well as
      current anti-angiogenic therapeutic strategies and their targets. We focus
      primarily on the role of key growth factors that are secreted by melanoma cells
      and known to trigger angiogenic responses, and their receptors as expressed on
      both endothelial and melanoma cells. Many of these growth factors function in
      synergy with receptors for extracellular matrix, integrins, and matrix
      metalloproteinases (MMPs). All of these systems of molecules are activated during
      major stages of angiogenesis such as endothelial migration, proliferation, and
      reorganization of surrounding extracellular matrix. The blockade of these
      molecules and their downstream pathways leads to inhibition of melanoma
      vascularization. Thus, these classes of molecules are essential for melanoma
      angiogenesis and, therefore, might serve as promising targets for therapeutic
      intervention. Many recently developed compounds targeting key pathways in
      angiogenesis are in their final stages of clinical trials.

PMID- 18083381
TI  - A world fit for children?

PMID- 18083382
TI  - FDA off-track on off-label drug promotion.

PMID- 18083383
TI  - A step-change for UK biomedicine.

PMID- 18083384
TI  - Artificial kidneys: progress and promise.

PMID- 18083385
TI  - Cardiac toxicity of sunitinib.

PMID- 18083386
TI  - Adjuvant chemotherapy of colorectal cancer.

PMID- 18083387
TI  - Prevention of hepatitis C in Japan: a lesson for us all.

PMID- 18083388
TI  - Preimplantation aneuploidy screening: a research tool for now.

PMID- 18083389
TI  - Clinical update: bariatric surgery.

PMID- 18083392
TI  - Ethical treatment of military detainees.

PMID- 18083393
TI  - Ethical treatment of military detainees.

PMID- 18083395
TI  - Treating clinically isolated syndromes suggestive of MS.

PMID- 18083397
TI  - Remote ischaemic preconditioning.

PMID- 18083398
TI  - Dabigatran versus enoxaparin after total hip replacement.

PMID- 18083399
TI  - Dabigatran versus enoxaparin after total hip replacement.

PMID- 18083401
TI  - Folic acid fortification and cancer risk.

PMID- 18083402
TI  - A wearable haemodialysis device for patients with end-stage renal failure: a
      pilot study.
AB  - BACKGROUND: More frequent haemodialysis can improve both survival and quality of
      life of patients with chronic kidney disease. However, there is little capacity
      in the UK to allow patients to have more frequent haemodialysis treatments in
      hospital and satellite haemodialysis units. New means of delivering haemodialysis
      are therefore required. Our aim was to assess the safety and efficiency of a
      wearable haemodialysis device. METHODS: Eight patients with end-stage kidney
      failure (five men, three women, mean age 51.7 [SD 13.8] years) who were
      established on regular haemodialysis were fitted with a wearable haemodialysis
      device for 4-8 h. Patients were given unfractionated heparin for anticoagulation,
      as they would be for standard haemodialysis. FINDINGS: There were no important
      cardiovascular changes and no adverse changes in serum electrolytes or acid-base
      balance. There was no evidence of clinically significant haemolysis in any
      patient. Mean blood flow was 58.6 (SD 11.7) mL/min, with a dialysate flow of 47.1
      (7.8) mL/min. The mean plasma urea clearance rate was 22.7 (5.2) mL/min and the
      mean plasma creatinine clearance rate was 20.7 (4.8) mL/min. Clotting of the
      vascular access occurred in two patients when the dose of heparin was decreased
      and the partial thromboplastin time returned towards the normal reference range
      in both of these patients. The fistula needle became dislodged in one patient,
      but safety mechanisms prevented blood loss, the needle was replaced, and
      treatment continued. INTERPRETATION: This wearable haemodialysis device shows
      promising safety and efficacy results, although further studies will be necessary
      to confirm these results.

PMID- 18083404
TI  - Adjuvant chemotherapy versus observation in patients with colorectal cancer: a
      randomised study.
AB  - BACKGROUND: The aim of the QUASAR trial was to determine the size and duration of
      any survival benefit from adjuvant chemotherapy for patients with colorectal
      cancer at low risk of recurrence, for whom the indication for such treatment is
      unclear. METHODS: After apparently curative resections of colon or rectal cancer,
      3239 patients (2963 [91%] with stage II [node negative] disease, 2291 [71%] with
      colon cancer, median age 63 [IQR 56-68] years) enrolled between May, 1994, and
      December, 2003, from 150 centres in 19 countries were randomly assigned to
      receive chemotherapy with fluorouracil and folinic acid (n=1622) or to
      observation (with chemotherapy considered on recurrence; n=1617). Chemotherapy
      was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of
      intravenous fluorouracil (370 mg/m2) with high-dose (175 mg) L-folinic acid or
      low-dose (25 mg) L-folinic acid. Until 1997, levamisole (12 courses of 450 mg
      over 3 days repeated every 2 weeks) or placebo was added. After 1997, patients
      who were assigned to receive chemotherapy were given fluorouracil and low-dose
      folinic acid only. The primary outcome was all-cause mortality. Analyses were
      done by intention to treat. This trial is registered with the International
      Clinical Trial Registry, number ISRCTN82375386. FINDINGS: At the time of
      analysis, 61 (3.8%) patients in the chemotherapy group and 50 (3.1%) in the
      observation group had missing follow-up. After a median follow-up of 5.5 (range 0
      10.6) years, there were 311 deaths in the chemotherapy group and 370 in the
      observation group; the relative risk of death from any cause with chemotherapy
      versus observation alone was 0.82 (95% CI 0.70-0.95; p=0.008). There were 293
      recurrences in the chemotherapy group and 359 in the observation group; the
      relative risk of recurrence with chemotherapy versus observation alone was 0.78
      (0.67-0.91; p=0.001). Treatment efficacy did not differ significantly by tumour
      site, stage, sex, age, or chemotherapy schedule. Eight (0.5%) patients in the
      chemotherapy group and four (0.25%) in the observation group died from non
      colorectal cancer causes within 30 weeks of randomisation; only one of these
      deaths was deemed to be possibly chemotherapy related. INTERPRETATION:
      Chemotherapy with fluorouracil and folinic acid could improve survival of
      patients with stage II colorectal cancer, although the absolute improvements are
      small: assuming 5-year mortality without chemotherapy is 20%, the relative risk
      of death seen here translates into an absolute improvement in survival of 3.6%
      (95% CI 1.0-6.0).

PMID- 18083405
TI  - Risk of authoritarianism: fibrinogen-transmitted hepatitis C in Japan.
AB  - In 1977, the US Food and Drug Administration revoked all licences for fibrinogen
      concentrate because of the risk for hepatitis infection and suspected lack of
      effectiveness. However, in Japan, fibrinogen concentrate was used routinely for
      treatment of obstetric bleeding until 1988. Even in 1997, academic texts by
      Japanese authorities in obstetrics still recommended that obstetricians use the
      product. An estimated 10 000 cases of hepatitis C infection are attributable to
      use of fibrinogen in Japan and are a result of authoritarianism that hindered
      effective policy changes. Scientists have a duty to refine repeatedly the quality
      of their evidence, and policymakers need to adjust existing policies continually
      to accord with the latest scientific evidence.

PMID- 18083403
TI  - Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib.
AB  - BACKGROUND: Sunitinib, a multitargeted tyrosine-kinase inhibitor, which is
      approved by both US and European Commission regulatory agencies for clinical use,
      extends survival of patients with metastatic renal-cell carcinoma and
      gastrointestinal stromal tumours, but concerns have arisen about its cardiac
      safety. We therefore assessed the cardiovascular risk associated with sunitinib
      in patients with metastatic gastrointestinal stromal tumours. METHODS: We
      retrospectively reviewed all cardiovascular events in 75 patients with imatinib
      resistant, metastatic, gastrointestinal stromal tumours who had been enrolled in
      a phase I/II trial investigating the efficacy of sunitinib. The composite
      cardiovascular endpoint was cardiac death, myocardial infarction, and congestive
      heart failure. We also examined sunitinib's effects on left ventricular ejection
      fraction (LVEF) and blood pressure. We investigated potential mechanisms of
      sunitinib-associated cardiac effects by studies in isolated rat cardiomyocytes
      and in mice. FINDINGS: Eight of 75 (11%) patients given repeating cycles of
      sunitinib in the phase I/II trial had a cardiovascular event, with congestive
      heart failure recorded in six of 75 (8%). Ten of 36 (28%) patients treated at the
      approved sunitinib dose had absolute LVEF reductions in ejection fraction (EF) of
      at least 10%, and seven of 36 (19%) had LVEF reductions of 15 EF% or more.
      Sunitinib induced increases in mean systolic and diastolic blood pressure, and 35
      of 75 (47%) individuals developed hypertension (>150/100 mm Hg). Congestive heart
      failure and left ventricular dysfunction generally responded to sunitinib being
      withheld and institution of medical management. Sunitinib caused mitochondrial
      injury and cardiomyocyte apoptosis in mice and in cultured rat cardiomyocytes.
      INTERPRETATION: Left ventricular dysfunction might be due, in part, to direct
      cardiomyocyte toxicity, exacerbated by hypertension. Patients treated with
      sunitinib should be closely monitored for hypertension and LVEF reduction,
      especially those with a history of coronary artery disease or cardiac risk
      factors.

PMID- 18083406
TI  - It started with a kiss (perhaps).

PMID- 18083407
TI  - Gun safety and social responsibility: a means to reduce maxillofacial trauma.

PMID- 18083408
TI  - Citation accuracy in the oral and maxillofacial surgery literature.
AB  - PURPOSE: Readers frequently assume that the references in an article published in
      a well-respected, peer-reviewed journal will be cited correctly. However,
      previous studies have shown that this is not always true. The purpose of this
      study was to evaluate the citation accuracy in 5 oral and maxillofacial surgery
      journals. MATERIALS AND METHODS: A search was done using PubMed
      (http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed) to locate the articles cited
      in 108 references in each journal. If the article could not be located, a search
      was done in the specific journal in the medical library. The references were then
      divided into those with major errors that prevented the article from being
      located and those with minor errors that still permitted the article to be found.
      RESULTS: There were a significant number of citations with major errors in each
      of the journals that made it impossible to find these articles. No correlation
      was found between the number of major or minor errors and the rank of the senior
      author or if the article was submitted from a non English-speaking country.
      CONCLUSIONS: This study shows that there needs to be a greater effort on the part
      of authors to provide accurate citations in their articles.

PMID- 18083409
TI  - Superiorly or inferiorly based "islanded" nasolabial flap for buccal mucosa
      defects reconstruction.
AB  - PURPOSE: This article describes the successful use of superiorly and inferiorly
      based subcutaneous pedicled flaps in the reconstruction of defects of the buccal
      mucosa by raising the flaps as skin islands, relying on a pedicle of subcutaneous
      tissue. PATIENTS AND METHODS: Nine procedures were performed on 9 patients for
      reconstruction of small to moderate defects of the central portion of the buccal
      mucosa. Four patients underwent superiorly based and 5 patients underwent
      inferiorly based "islanded" nasolabial flap reconstruction. RESULTS: All flaps
      healed without evidence of infection, dehiscence, or necrosis. The choice of
      superiorly or inferiorly based "islanded" nasolabial flap did not affect the
      success of the final result; instead it helped decrease the trismus associated
      with these resections. CONCLUSIONS: The inferiorly or superiorly based nasolabial
      "islanded" flaps provide reliable coverage of small and intermediate sized
      defects of the buccal mucosa, improving mouth opening.

PMID- 18083410
TI  - Effect of chemotherapy on primary mucosa-associated lymphoid tissue lymphoma of
      the orbit.
AB  - PURPOSE: To present a treatment plan for localized mucosa-associated lymphoid
      tissue lymphoma of the orbit in order to preserve vital structures and function
      from the side effects of radiotherapy. MATERIALS AND METHODS: Study of 2 clinical
      cases by means of clinical and radiologic examination, with 2 and 3 years follow
      up, respectively. RESULTS: Immediate remission of the disease after 6 cycles of
      chemotherapy, with no signs of recurrence after 2 and 3 years. Clinical
      examination of the oculomotor mechanism and visual activity gave excellent
      results. CONCLUSION: Although radiotherapy is preferable for localized
      lymphoproliferative lesions, chemotherapy should also be considered as an
      effective treatment that preserves the integrity and function of the ocular
      adnexa.

PMID- 18083411
TI  - Clinical investigation for bilateral cleft lip repair: modified functional
      bilateral cleft lip cheilorrhaphy.
AB  - PURPOSE: To obtain better operative results, a modified functional bilateral
      cleft lip (BCL) cheilorrhaphy was designed and used on 131 BCL patients to
      evaluate the clinical effectiveness in this clinical investigation. A new
      surgical method would be provided for BCL patients. PATIENTS AND METHODS: Based
      on the experiences and advantages of the commonly used self-longation and
      elongation surgical methods for BCL repair, a new surgical method was designed
      for BCL patients. During the operation, this modified functional BCL
      cheilorrhaphy emphasized the operative design, anatomy and reposition of musculus
      orbicularis orbis, management of the maxilla, and reparation of vermilion of the
      lip. This method was used to repair 131 BCL patients, and the conditions and
      results of errhysis, swelling, and healing of tresis vulnus were observed and
      evaluated. RESULTS: This modified functional BCL cheilorrhaphy was used
      successfully from January 2002 to July 2005 on 131 BCL patients. The wounds of
      all patients with BCL who joined this study healed very well without any
      hematoma, infection, or wound decohesion. All of the patients showed symmetric
      peak of Cupid's bow, obvious philtrum notch, full vermilion of the lip, little
      scarring, and satisfactory contour. During functional activity, bilateral upper
      lip was symmetric, coordinated, and balanced. CONCLUSIONS: The clinical results
      showed that modified functional BCL cheilorrhaphy may be accepted as a good
      selective surgical technique for BCL patients, and is worth generalization and
      application.

PMID- 18083412
TI  - Cytokine and clinical predictors for treatment outcome of visually guided
      temporomandibular joint irrigation in patients with chronic closed lock.
AB  - PURPOSE: This study investigates selected predictors for clinical outcome of
      temporomandibular joint (TMJ) irrigation in patients with chronic closed lock
      (CCL). PATIENTS AND METHODS: Fifty-six patients with unilateral CCL, who
      underwent a visually guided TMJ irrigation (VGIR), were enrolled in this study.
      They were divided into either successful (s-group; n = 38) or unsuccessful groups
      (u-group; n = 18), according to the clinical success criteria. The investigated
      predictive factors were age, gender, duration of symptoms before the VGIR,
      preoperative painless range of mandibular motion, preoperative self-evaluated TMJ
      pain on visual analog scale (VAS), severity of arthroscopically observed
      pathologies, and presence and concentrations of a set of pro- and anti
      inflammatory cytokines (ie, tumor necrosis factor [TNF]-alpha, interleukin [IL]
      1beta, IL-6, IL-8, IL-12, and IL-10) in the aspirated synovial fluid (A-SF).
      Several comparative analyses and logistic regression analyses were used for
      statistical studies. RESULTS: The preoperative VAS score, detection rate of IL-8,
      and concentrations of IL-6 and IL-8 in the A-SF were significantly higher in the
      u-group (P < .05). Conversely, the detection rate and concentrations of IL-10
      were significantly higher in the s-group (P < .05). The multivariate adjusted
      odds ratio (OR) showed that the detectable IL-10 in the A-SF (OR, 10.882; P =
      .047) is significantly predictive for a successful VGIR. CONCLUSIONS: The
      presence of IL-10 in the A-SF is a significant predictor of successful outcome of
      TMJ irrigation for CCL. Severe TMJ pain and detectable IL-6 or IL-8 in the A-SF
      seem to indicate a poor outcome after TMJ irrigation.

PMID- 18083413
TI  - Posterior vertical deficiencies of the mandible: presentation of a new corrective
      technique and retrospective study of 21 cases.
AB  - PURPOSE: The hyperdivergent (high-angle forms of Class II) dentoskeletal
      deformities are difficult entities to treat. The purpose of this study was to
      describe and evaluate the use of a new surgical procedure to lower the posterior
      portion of the occlusal plane during a sagittal split osteotomy of the mandibular
      ramus, to correct a Class II malocclusion resulting from insufficient development
      of the mandibular ramus. PATIENTS AND METHODS: During a sagittal split osteotomy
      of the mandibular ramus, the pterygomasseteric sling was completely incised in 21
      patients, to treat Class II malocclusion with vertical ramus deficiency. The
      patients were evaluated clinically, radiologically, and cephalometrically.
      RESULTS: In all cases, the posterior occlusal plane was successfully lowered,
      with stable occlusal results, both vertically and sagittally. An increase in the
      vertical dimension of the ramus remains somewhat more difficult to document.
      CONCLUSIONS: Sagittal split osteotomy of the mandibular ramus with complete
      incision of the pterygomasseteric sling makes it possible to lower the posterior
      occlusal plane in cases of posterior vertical mandibular deficiency. This
      technique, which offers a nonexternal approach, represents a useful additional
      option for the treatment of these dysmorphoses.

PMID- 18083414
TI  - Subtarsal approach for orbital floor repair: a long-term follow-up of 12 cases in
      a Jordanian teaching hospital.
AB  - PURPOSE: To evaluate the long-term functional and esthetic outcomes of using the
      subtarsal approach for orbital trauma patients in a group of Jordonian patients.
      PATIENTS AND METHODS: Twelve patients treated using the subtarsal approach for
      orbital floor fractures in the Oral and Maxillofacial Surgery unit at the Jordan
      University Hospital were involved. Aspects evaluated included: the distance
      between scar and lower lid lash margin, scar length, esthetic appearances of the
      scar, lid edema, scleral show, ectropion, lagophthalmous, epiphora,
      subconjunctival injections, and keratoconjunctivitis. RESULTS: Half the cases
      were the result of road traffic accidents. Follow-up time ranged from 10 to 73
      months (mean +/- SD, 37.25 +/- 23.7 months). The postoperative outcome was
      favorable; 1 scar was noticeable, but was not hypertrophic. One patient suffered
      from scleral show that was associated with subconjunctival injections. One
      patient suffered from mild lid edema and 1 had keratoconjunctivitis. No other
      complications were recorded and patients were satisfied with the outcome.
      CONCLUSIONS: The subtarsal approach is a safe and simple to perform procedure for
      treating orbital floor fractures. It results in a good surgical outcome
      functionally and esthetically.

PMID- 18083415
TI  - Hemostatic management of tooth extractions in patients on oral antithrombotic
      therapy.
AB  - PURPOSE: We examined hemostatic management for tooth extraction in patients
      maintained on oral antithrombotic therapy. PATIENTS AND METHODS: Subjects
      comprised 270 patients, with 134 receiving warfarin alone, 49 receiving warfarin
      with additional antiplatelet drugs, and the remaining 87 receiving antiplatelet
      drugs alone. In patients administered warfarin alone, international normalized
      ratio (INR) was 1.5 to 1.99 in 67 patients, 2.0 to 2.49 in 42, 2.5 to 2.99 in 21,
      and 3.0 to 3.7 in 4. A total of 513 teeth were extracted on 306 occasions. All
      teeth were extracted without reducing the usual antithrombotic therapy, and
      oxidized cellulose was applied and suturing was performed for local hemostasis.
      RESULTS: Postoperative hemorrhage occurred in 11 of 306 occasions of tooth
      extractions (3.6%). These involved 7 patients on warfarin monotherapy and 2 on
      combination therapy with warfarin and antiplatelet drugs, with INR between 1.50
      and 2.49. Incidence of postoperative hemorrhage was unrelated to INR, and no
      significant differences were identified between warfarin monotherapy and
      combination therapy. The remaining 2 patients who experienced hemorrhage were
      administered antiplatelet drugs alone. CONCLUSION: A sufficient hemostasis can be
      obtained in most cases of tooth extraction under anticoagulant therapy with
      warfarin (INR <3.0) and antiplatelet drugs. Moreover, appropriate local
      hemostatic methods can be successful when postoperative hemorrhage occurs.

PMID- 18083416
TI  - Pediatric craniofacial trauma.
AB  - PURPOSE: Maxillofacial and skull fractures occur with concomitant injuries in
      pediatric trauma patients. The aim of this study was to determine the causes and
      distributions of maxillofacial and skull fractures as well as concomitant
      injuries of pediatric patients in Switzerland. Results were compared with
      worldwide studies. MATERIALS AND METHODS: A retrospective review was conducted of
      291 pediatric patients with maxillofacial and skull fractures presenting to a
      level-I trauma center over a 3-year span. Data concerning the mechanism of the
      accident and the topographic location of the injuries were analyzed. RESULTS: The
      most common causes were falls (64%), followed by traffic (22%) and sports-related
      accidents (9%). Fifty-four percent of the fractures occurred in the skull vault
      and 37% in the upper and middle facial third. One third of the patients (n = 95)
      suffered concomitant injuries, mostly cerebral concussions (n = 94). CONCLUSIONS:
      The spectrum of craniofacial injuries is related to the specific developmental
      stage of the craniofacial skeleton. It is probable that national prevention
      programs will have a positive effect on reducing the incidence of falls.
      Standardization of studies is needed for international comparison.

PMID- 18083417
TI  - Condylectomy and costochondral graft reconstruction for treatment of active
      idiopathic condylar resorption.
AB  - PURPOSE: The purpose of this study was to evaluate the outcomes in patients with
      active bilateral idiopathic condylar resorption treated by condylectomy and
      costochondral graft (CCG) reconstruction. PATIENTS AND METHODS: This was a
      retrospective evaluation of 15 consecutive patients treated at Massachusetts
      General Hospital from 1999 to 2004 who had: 1) active bilateral idiopathic
      condylar resorption confirmed by clinical examination, plain radiographs, and
      technetium-99 bone scan; 2) adequate documentation; and 3) a minimum of 12 months
      follow-up. Patients with an identifiable cause of condylar resorption such as
      rheumatoid or degenerative arthritis, trauma, or steroid use, or who had less
      than 12 months follow-up were excluded. Preoperative, immediate postoperative, 6
      month, 12-month, and latest follow-up clinical examinations, lateral
      cephalograms, and panoramic radiographs were used to evaluate the outcomes.
      Inferior alveolar and marginal mandibular nerve function, jaw motion, and
      occlusion were evaluated by history and physical examination. All patients
      underwent bilateral condylectomy and CCG reconstruction. RESULTS: There were 13
      female and 2 male patients with a mean age of 24 years. Mean follow-up was 34
      months (range, 12 to 84). Preoperatively, all patients had Class II malocclusion:
      mean overjet 6.2 mm and mean anterior open bite -2.65 mm. At latest postoperative
      follow-up, all patients showed Class I occlusion with no anterior open bite, a
      stable and reproducible occlusion, and a normal range of TMJ motion with a mean
      maximal incisal opening of 39 mm. CONCLUSION: The results of this study indicate
      that a stable and satisfactory outcome is achievable in patients with active
      idiopathic condylar resorption treated by condylectomy and CCG reconstruction.

PMID- 18083418
TI  - Analysis of 115 mandibular angle fractures.
AB  - PURPOSE: This retrospective study reviewed cases of fractures of the mandibular
      angle to identify personal data, social traits, fracture characteristics,
      treatment modalities, and postoperative complications. PATIENTS AND METHODS: From
      April 1999 until July 2004, 114 patients were treated for 115 fractures of the
      mandibular angle by the Division of Oral and Maxillofacial Surgery at Piracicaba
      Dental School-Unicamp, in Brazil. RESULTS: More angle fractures were observed in
      Caucasian (55%) men (89%) with some kind of drug addiction (62%). Patient mean
      age was 27 years. The majority of fractures in this study were sustained in
      altercations, including gunshot wounds (43%), followed by vehicle accidents,
      including bicycles and being struck by a car (39%). Open fractures were the most
      frequent (90%), with prevalence of the left side (57%). Only 1 patient sustained
      bilateral angle fractures. Ninety-seven patients (85%) underwent open reduction.
      Complications occurred in 19 patients (17%); 10 (9%) were infections. Of the
      total number of complications, 3 underwent another surgical intervention for
      refixation. The factors that contributed to the development of postoperative
      complications were social risks that included alcohol abuse, smoking, and
      intravenous and nonintravenous drug abuse. CONCLUSIONS: Angle fracture management
      outcomes are affected by many factors beyond method of fixation.

PMID- 18083419
TI  - Etiology of temporomandibular joint ankylosis secondary to condylar fractures:
      the role of concomitant mandibular fractures.
AB  - PURPOSE: The purpose of the study was to explore the association between condylar
      fractures and temporomandibular joint (TMJ) ankylosis in a sample from 1 hospital
      in China. PATIENTS AND METHODS: All patients treated for post-traumatic TMJ
      ankylosis in a 5-year period at Peking University, School of Stomatology, who had
      sufficient information available were included. Demographic information and
      details of their original injury and resultant ankylosis were tabulated and
      analyzed by descriptive statistics. RESULTS: Twenty-five patients with 40
      ankylosed joints met the inclusion criteria (15 were bilateral). The majority of
      patients were male, and ranged from 5 to 52 years of age with a mean of 23 years.
      Twenty-five of 40 cases were the result of a sagittal fracture of the condyle,
      where the medial pole was fractured off. Nineteen ankylosed joints (47.5%) showed
      lateral or superolateral displacement of the lateral aspect of the ramus/condylar
      process. Sixteen of 25 patients (64%) had fractures of the mandible other than
      condylar fractures located in the anterior mandible that were often untreated or
      not properly reduced. Fifty percent of the patients had widening of face or
      crossbites. CONCLUSIONS: The results of this study indicate that the combination
      of an intracapsular fracture with concomitant widening of the mandible leads to
      the lateral pole of the condyle or the condylar stump to become displaced
      laterally or superolaterally in relation to the zygomatic arch, where it fuses.
      Proper treatment of the anterior mandibular fracture(s) may help prevent the
      development of TMJ ankylosis in such patients.

PMID- 18083420
TI  - The relationship between measures of nutritional status and masticatory function
      in untreated patients with head and neck cancer.
AB  - PURPOSE: Nearly 40% of newly diagnosed patients with head and neck cancer are
      malnourished before treatment begins with many researchers ascribing the
      malnutrition to a paucity of teeth. We attempted to determine if inadequate
      numbers of occluding pairs of teeth, rather than mere numbers of teeth, in newly
      hospitalized, untreated head and neck cancer patients correlates with nutritional
      status parameters used to identify those at heightened risk for malnutrition
      related complications. PATIENTS AND METHODS: Patients and cancer-free, matched
      controls were evaluated for malnutrition (body mass index < or = 20 [weight
      (kg)/height (m2)]), serum albumin < or = 2.7 g/dL, hemoglobin < or = 11.9 g/dL,
      and total lymphocyte count < or = 1,449/muL), and inadequate numbers of occluding
      pairs of teeth variably defined as less than 5 "posterior pairs" of occluding
      teeth or less than 6 or 7 "total pairs" of occluding teeth. RESULTS: Head and
      neck cancer patients had significantly lower body mass index (P = .005) and total
      lymphocyte count (P = .019) than controls, but there were no significant
      correlations between the nutritional and dental variables in either group.
      CONCLUSIONS: Untreated head and neck cancer patients frequently have nutritional
      status parameters indicating heightened risk for malnutrition-related
      complications but inadequate masticatory function is not a causative factor.

PMID- 18083421
TI  - The effect of platelet-altering medications on bleeding from minor oral surgery
      procedures.
AB  - PURPOSE: This study was performed to assess the extent of bleeding from minor
      oral surgical procedures in patients taking platelet-altering medications. They
      were compared with patients who were not taking platelet-altering medicines to
      assess differences in extent of blood loss. MATERIALS AND METHODS: A prospective
      observational study design was used to quantitatively assess the amount and
      severity of bleeding encountered with dentoalveolar surgery in 2 groups. The
      experimental group consisted of people taking therapeutic doses of platelet
      altering medications, and the control group was composed of patients who had not
      taken a platelet-altering medication for at least 10 days prior to surgery.
      Surgical blood loss was measured, and the groups were compared for statistically
      significant differences in blood loss. RESULTS: There was no difference in blood
      loss detected between the experimental or control groups. No bleeding
      complications were encountered. CONCLUSION: Our data suggest that patients on
      aspirin and NSAIDs can safely undergo routine minor outpatient oral surgical
      procedures without modification of their platelet-altering medication.

PMID- 18083422
TI  - Evaluation of the soft and hard tissue changes after anterior segmental osteotomy
      on the maxilla and mandible.
AB  - PURPOSE: The purpose of this study was to determine the relationship between the
      changes of soft and hard tissues after modified anterior segmental osteotomy on
      the maxilla and mandible and to evaluate unintended facial changes using
      cephalometric and photometric analyses. MATERIALS AND METHODS: The subjects
      included 29 women and 1 man (22 to 50 years of age) who were diagnosed as
      bialveolar or bimaxillary protrusion and underwent modified anterior segmental
      osteotomy on the maxilla and mandible. Lateral cephalograms and lateral and
      frontal photographs taken preoperatively and postoperatively were analyzed.
      RESULTS: There was a significant change in all soft and hard tissue parameters
      except the labiomental angle. The ratio of upper lip to maxillary incisor
      retraction was 0.67:1 and the ratio of lower lip to mandibular incisor retraction
      was 0.89:1. Nasolabial angle and philtrum length were increased, and vermilion
      length and lip width were decreased. Nasal change could be kept as small as
      possible, although slight widening of the nasal width and anti-tip rotation of
      the nasal tip were observed. CONCLUSION: Anterior segmental osteotomy might be
      recommended as the treatment modality of choice in patients with bimaxillary
      and/or dentoalveolar protrusion. Because the technique is simple, postoperative
      complications are minimal, relapse is limited, and soft tissue changes in
      response to surgery are more predictable.

PMID- 18083423
TI  - Transverse displacement of the proximal segment after bilateral sagittal
      osteotomy: a comparison of lag screw fixation versus miniplates with monocortical
      screw technique.
AB  - PURPOSE: The purpose of the present study was to compare lag screw fixation
      versus miniplates with monocortical screw technique with respect to the amount of
      transverse displacement of the proximal segment after bilateral sagittal
      osteotomy (BSO) for mandibular advancement surgery. PATIENTS AND METHODS: We
      conducted a multicenter, retrospective investigation of 82 patients who underwent
      a mandibular advancement with BSO and rigid internal fixation. Forty-five
      patients from Denmark and Sweden, the miniplate fixation group, received a rigid
      fixation consisting of miniplates with monocortical screws. Thirty-seven patients
      from the Mayo Clinic, the lag screw fixation group, received a rigid fixation
      with lag screw fixation of the mandible. The transverse displacement and
      angulation of the proximal segments were measured on posterior-anterior
      cephalometric radiographs, using the best-fit method. RESULTS: After BSO, 44 of
      45 patients in the miniplate fixation group showed an increased transverse
      intergonion distance with a mean of 5.0 mm and an increase transverse interramus
      width with a mean of 2.4 mm. Thirty-six of 37 patients in the lag screw fixation
      group had an increased intergonial width with a mean of 5.6 mm, and 35 of 37
      patients showed an increased transverse interramus width with a mean of 3.3 mm. t
      tests showed that there were no significant differences between the 2 groups with
      respect to these 2 variables. CONCLUSIONS: Our results indicate that transverse
      displacements of the proximal segments occur after BSO surgery with both
      miniplate or lag screw fixation technique. Attention and future studies should
      focus on possible complications that transverse displacement of the proximal
      segment may cause.

PMID- 18083424
TI  - Fixed-prosthetic implant restoration of the edentulous maxilla: a systematic
      pretreatment evaluation method.

PMID- 18083425
TI  - Diagnostic and therapeutic approach to sialoblastoma of submandibular gland: a
      case report.

PMID- 18083426
TI  - Maxillary anterior segmental advancement of hypoplastic maxilla in cleft patients
      by distraction osteogenesis: report of 2 cases.

PMID- 18083427
TI  - Traumatic pseudoaneurysm of the superficial temporal artery in a pediatric
      patient: a case report.

PMID- 18083428
TI  - Salivary mediated autoinoculation of herpes simplex virus on the face in the
      absence of "cold sores," after trauma.

PMID- 18083429
TI  - Treatment of mandibular arteriovenous malformation by transvenous embolization
      through the mental foramen.

PMID- 18083430
TI  - Squamous cell carcinoma of the tongue after bone marrow transplant and graft
      versus-host disease: a case report and review of the literature.

PMID- 18083431
TI  - Multiple bilateral tonsilloliths: case report.

PMID- 18083432
TI  - Yolk sac tumor of the mandible.

PMID- 18083433
TI  - Synovial sarcoma of the tongue: report of a case and review of the literature.

PMID- 18083434
TI  - Synovial sarcoma in the oral and maxillofacial region: report of 4 cases and
      review of the literature.

PMID- 18083435
TI  - Malposed teeth in the pterygomandibular space: report of 2 cases.

PMID- 18083436
TI  - Three-dimensional identification of vascular compression in eagle's syndrome
      using computed tomography: case report.

PMID- 18083437
TI  - Ultrasonic bone cut part 1: State-of-the-art technologies and common
      applications.

PMID- 18083438
TI  - Ultrasonic bone cut part 2: State-of-the-art specific clinical applications.

PMID- 18083439
TI  - Treatment of bone defects produced by lower molar extraction using ultrasound
      harvested autologous bone grafts.

PMID- 18083440
TI  - F-18 positron emission tomography and computed tomography image-fusion for image
      guided detection of local recurrence in patients with head and neck cancer using
      a 3-dimensional navigation system: a preliminary report.

PMID- 18083441
TI  - High cervical transmasseteric anteroparotid approach for open reduction and
      internal fixation of condylar fracture.

PMID- 18083442
TI  - Bone marrow edema: mild or nascent variant of ischemic bone disease.

PMID- 18083444
TI  - Mortality from leading causes by education and race in the United States, 2001.
AB  - BACKGROUND: Low educational attainment is a marker of socioeconomic status that
      correlates strongly with higher death rates from many conditions. No previous
      studies have analyzed national data to measure the number of deaths associated
      with lower education among working-aged adults (25-64 years) by race or
      ethnicity. Furthermore, no previous studies have examined comprehensively the
      relationship of education to cause-specific and all-cause mortality in the three
      largest racial or ethnic groups in the United States using national data.
      METHODS: Age-standardized, race/ethnicity-specific death rates from all causes
      and the 15 leading causes were measured among men and women aged 25-64 years by
      level of education based on U.S. national mortality data in 2001. The total
      number of deaths that potentially could be avoided among people aged 25-64 years
      was estimated by applying the mortality rates among college graduates (within
      each 5-year category of age, gender, and race/ethnicity) to each of the less
      educated subpopulations. All analyses were performed in 2007. RESULTS: Nearly
      half (48%) of all deaths among men aged 25-64 years (white, black, and Hispanic),
      and 38% of all deaths in women would not have occurred in this age range if all
      segments of the population experienced the death rates of college graduates.
      Black men and women had the highest death rates from all causes combined and from
      many specific causes at nearly all levels of education, and the largest average
      life years lost before age 65 years. However, the total number of deaths
      associated with low education status was not confined to any single racial group.
      About 161,280 deaths in whites, 40,840 deaths in blacks, and 13,162 deaths in
      Hispanics in this age range were associated with educational disparity.
      CONCLUSIONS: Potentially avoidable factors associated with lower educational
      status account for almost half of all deaths among working-aged adults in the
      U.S.; these deaths are not confined to any single racial or ethnic group. These
      findings highlight the need for greater attention to social determinants of
      health.

PMID- 18083445
TI  - Income and racial disparities in access to public parks and private recreation
      facilities.
AB  - BACKGROUND: Disparities in health outcomes and health behaviors may be partially
      explained by neighborhood environments that are poor in resources that could
      support healthy behaviors. The purpose of this study was to test the hypothesis
      that low-income and high-minority neighborhoods have less access to public parks,
      open space, and private recreation facilities. METHODS: From 2004 to 2005, an
      inventory of 351 private recreation facilities and 465 public parks was conducted
      in 833 Census block groups in Maryland. In 2-way ANCOVAs, numbers of private
      facilities and public parks, as well as maximum park size, were studied in
      relation to categories of median income and percent non-white population in the
      block groups. RESULTS: For the number of private recreation facilities, there was
      no significant effect of income or percent minority. For number and size of
      parks, the interaction between income and percent minority was significant. Mixed
      race neighborhoods had the highest number of parks, regardless of income. Low-
      and middle-income groups living in mostly-white block groups and high-income
      groups living in mostly-minority block groups had the lowest access to public
      parks. CONCLUSIONS: The expected deprivation of recreation facilities in low
      income and high-minority neighborhoods was not found. There are exceptions to the
      inequalities found nationally, so the policies or practices associated with a
      fairer distribution of recreation resources in some local areas need to be better
      understood.

PMID- 18083446
TI  - Availability of recreational resources in minority and low socioeconomic status
      areas.
AB  - BACKGROUND: Differences in availability of recreational resources may contribute
      to racial and socioeconomic status (SES) disparities in physical activity.
      Variations in the location and density of recreational resources were examined by
      SES and racial composition of neighborhoods. METHODS: Densities of resources
      available in recreational facilities and parks were estimated for census tracts
      between April 2003 and June 2004 in North Carolina, New York, and Maryland using
      kernel estimation. The probability of not having a facility or park was modeled
      by tract racial composition and SES, adjusting for population and area, using
      binomial regression in 2006. Mean densities of tract resources were modeled by
      SES and racial composition using linear regression. RESULTS: Minority
      neighborhoods were significantly more likely than white neighborhoods not to have
      recreational facilities (relative probability [RP]=3.27 [95% CI=2.11-5.07] and
      8.60 [95% CI=4.48-16.51], for black and Hispanic neighborhoods, respectively).
      Low-income neighborhoods were 4.5 times more likely to not have facilities than
      high-income areas (95% CI=2.87-7.12). Parks were more equitably distributed. Most
      resources located in recreational facilities required a fee and were less dense
      in minority and low-income areas. Those located inside parks were usually free to
      use, sports-related, and denser in poor and minority neighborhoods. CONCLUSIONS:
      Recreational facilities and the resources they offer are not equitably
      distributed. The presence of parks in poor and minority areas suggest that
      improving the types and quality of resources in parks could be an important
      strategy to increase physical activity and reduce racial/ethnic and socioeconomic
      disparities.

PMID- 18083447
TI  - The childcare environment and children's physical activity.
AB  - BACKGROUND: With increased numbers of children attending child care, this setting
      presents an ideal opportunity to promote physical activity and the early
      development of healthy behaviors. The purpose of this study was to examine the
      relationships between the childcare environment and physical activity behavior of
      preschool children. METHODS: Aspects of the environment hypothesized to influence
      children's physical activity were assessed in 20 childcare centers using the
      Environment and Policy Assessment and Observation (EPAO) instrument. Physical
      activity behavior was assessed over 2 days using direct observation. RESULTS:
      Children in centers with supportive environments achieved more moderate-to
      vigorous physical activity (15% of observations vs 9%; effect size [ES]=1.17),
      spent less time in sedentary activities (50% vs 61%; ES=-1.52), and had higher
      mean physical activity levels (2.68 vs 2.43; ES=1.41) compared to centers with
      less supportive environments. Facets of the physical and social environment
      related to physical activity behavior included active opportunities, portable
      play equipment, fixed play equipment, sedentary environment, and physical
      activity training and education. CONCLUSIONS: Previous research indicates that
      the childcare center that children attend significantly affects physical activity
      behavior. The current findings extend this evidence by identifying aspects of the
      childcare environment that relate to the physical activity behavior of children.
      These factors should be considered when identifying determinants of physical
      activity and designing interventions.

PMID- 18083448
TI  - Linking dating violence, peer violence, and suicidal behaviors among high-risk
      youth.
AB  - BACKGROUND: Gaps in the understanding of how different types of violent behavior
      are linked have limited the ability to design violence prevention efforts that
      can address multiple types of violence. The objective of this study was to
      quantify the associations among suicide attempts, and date and peer violence
      victimization and perpetration and to determine any differences in these
      associations by gender. METHODS: Analyses, computed in 2006 and 2007, used data
      from the Youth Violence Survey conducted in 2004. This survey was administered to
      over 80% of public school students in grades 7, 9, 11, and 12 (N=4131) in a high
      risk, urban school district. Analyses were restricted to adolescents who dated in
      the past year (n=2888). Five forms of violent behaviors (i.e., dating violence
      perpetration, dating violence victimization, peer violence perpetration, peer
      violence victimization, and suicide attempts) were examined. RESULTS: Peer
      violence victimization was the most common type of violence reported (33.0%),
      followed by date violence victimization (30.7%), peer violence perpetration
      (29.9%), date violence perpetration (24.8%), and suicide attempts (11.2%). Among
      all students, 9.8% reported involvement in at least four of the five violent
      behaviors examined. All five forms of violent behaviors were associated. The
      highest ORs were observed for victimization and perpetration within either the
      dating or peer context. However, associations across contexts were also observed.
      CONCLUSIONS: There is a substantial overlap among different forms of violent
      behavior, suggesting that additional research is needed to better understand the
      factors that contribute to involvement in multiple forms of violence.

PMID- 18083449
TI  - All-terrain vehicle-related hospitalizations in the United States, 2000-2004.
AB  - OBJECTIVES: To estimate the incidence of all-terrain vehicle (ATV)-related injury
      hospitalizations in the United States from 2000 through 2004, and to describe the
      types of injuries and associated hospital costs for the entire population.
      METHODS: Data for 2000 through 2004 were obtained from the Healthcare Cost and
      Utilization Project (HCUP) Nationwide Inpatient Sample--a stratified probability
      sample of 1004 community hospitals from 37 states. ATV injuries were defined by
      ICD-9-CM external cause of injury codes within E821. Variables included age,
      gender, primary diagnoses, patient disposition, primary payer, and hospital
      charges. Data were analyzed in 2007. RESULTS: There were an estimated 58,254 ATV
      related hospitalizations, increasing 90% over the 5-year period. Eighty percent
      were men. Thirty percent of the cases involved youth under age 18, and 8% were
      over age 60. Passengers accounted for 9% of the hospitalizations. Eighty-five
      percent were routinely discharged to home while 13% required long-term
      rehabilitation or home health care. Payers included private insurance (62%),
      Medicaid/Medicare (19%), and self-pay (12%). Rural hospitals treated 23% of the
      cases and urban teaching hospitals 47%. Estimated total hospital charges were
      about $1.1 billion (20% paid from public funds) with an average charge per
      patient of $19,671. Leading injuries included fractures of lower limbs (22%; mean
      hospital charges of $19,626), other fractures (15%; $18,873), and intracranial
      injuries (14%; $26,906). The overall hospital admission rate was 4.4 per 100,000
      population with variation by year, gender, and age. CONCLUSIONS: Voluntary
      industry and government safety efforts have had little impact on the increasing
      incidence and cost of ATV injuries. Renewed prevention efforts to making ATV
      riding safer are warranted.

PMID- 18083450
TI  - Uptake of pneumococcal conjugate vaccine among children in the 1998-2002 United
      States birth cohorts.
AB  - BACKGROUND: Routine childhood immunization with pneumococcal conjugate vaccines
      (PCV7s) began in 2000 in the United States. Despite vaccine shortages, reductions
      in invasive pneumococcal disease occurred rapidly during 2000-2002. Age
      appropriate PCV7 coverage was estimated and characteristics associated with
      undervaccination were identified for children in the 1998-2002 birth cohorts.
      METHODS: Data were analyzed for 85,135 children aged 19-35 months in the 2001
      2004 National Immunization Surveys. To obtain PCV7 coverage estimates by birth
      cohorts, a pooled analysis was conducted by combining individual survey years
      that sampled children with appropriate birth dates. Logistic regression models
      were used to identify factors associated with age-appropriate vaccination.
      RESULTS: The proportion of children receiving the primary 3-dose PCV7 series by
      age 12 months increased from 45.5% (+/-0.6) among children born in 2000 to 62.1%
      (+/-0.7) among those born in 2002. By age 24 months, an estimated 30.7% (+/-0.6),
      38.0% (+/-0.6), and 49.0% (+/-1.1) of children born in 2000, 2001 and 2002,
      respectively, had received all four PCV7 doses; however, only 15.0% (+/-0.4),
      16.1% (+/-0.4) and 24.4% (+/-0.6) of children were age-appropriately immunized.
      Among children born in 1998 and 1999, 10.1% +/-0.5) and 37.6% (+/-0.7),
      respectively, received one or more catch-up doses during their second year of
      life. Lower age-appropriate PCV7 coverage was independently associated with black
      race, Hispanic ethnicity, receiving vaccinations from public health providers,
      and low household income. CONCLUSIONS: The dramatic reductions in pneumococcal
      related diseases from direct and indirect vaccine effects occurred when few
      children had received the recommended complete vaccine schedule, and there were
      substantial racial and socioeconomic disparities in coverage.

PMID- 18083451
TI  - The impact of smoking-cessation intervention by multiple health professionals.
AB  - BACKGROUND: Smokers have contact with many different types of health
      professionals. The impact of tobacco intervention by multiple types of heath
      professionals is not known. METHODS AND MATERIALS: As part of the 2003 Minnesota
      Adult Tobacco Survey, smokers (n=1723) reported on tobacco treatment by medical
      doctors, nurses, dentists, pharmacists, or other health professionals. This
      analysis examined: (1) smokers' report of tobacco intervention by different types
      of healthcare providers, (2) the proportion of smokers who report intervention by
      multiple provider types, and (3) the relationship between smokers' report of
      intervention by multiple provider types and readiness to quit, quit attempts, and
      recent quitting. RESULTS: Among past-year smokers, 65% had visits with two or
      more types of health professionals. Among smokers who visited health
      professionals (n=1523), only 34% reported being asked about smoking by two or
      more types of professionals. Among current smokers (n=1324), advice or assistance
      from more than one type of professional was uncommon (26% and 7%, respectively).
      Being asked about smoking by two or more types of professionals substantially
      increased the odds of recent quitting (OR=2.37; 95% CI=1.15-4.88). Among current
      smokers, being advised to quit by two or more types of professionals increased
      the odds of having made a quit attempt in the past year (OR=2.92; 95% CI=1.56
      5.45) or intending to quit in the next 6 months (OR=2.17; 95% CI=1.10-4.29).
      CONCLUSIONS: Smoking-cessation interventions by more than one type of health
      professional have the potential to substantially increase quitting and readiness
      to quit in the population.

PMID- 18083452
TI  - Did news reporters get it right? Translation of the 2002 hormone study findings.
AB  - BACKGROUND: The news media play a critical role in communicating health
      information to the public. The unexpected findings in July 2002 about increased
      health risks associated with hormone therapy provided an opportunity to examine
      the process of translating scientific findings to reporters through communication
      intermediaries and appraise subsequent reporting in newspapers in the United
      States. METHODS: Using qualitative research software, a qualitative analysis was
      conducted in 2006 to consider four types of messages: (1) hormone therapy health
      risks outweighed benefits (balance); (2) adverse hormone therapy health outcomes
      (health risk); (3) positive hormone therapy health outcomes (benefit); and (4)
      risk level (magnitude). The print materials analyzed included the original 2002
      Journal of American Medical Association (JAMA) article and editorial; JAMA and
      National Institutes of Health (NIH) press releases; the NIH press conference
      transcript; and 198 articles about hormone therapy in 22 U.S. newspapers
      published from July to September 2002. RESULTS: The major study finding that
      hormone therapy risks outweighed benefits was reported consistently and
      accurately. Analyses of language and numbers on risk magnitude, and its
      interpretation revealed some variability, both within the translation materials
      and news stories. When risk numbers were included in newspaper stories, absolute
      risk was used more often than relative risk. CONCLUSIONS: Despite much criticism
      of journalists' coverage of health issues, U.S. newspaper reporting about hormone
      therapy in 2002 was generally consistent. Several translational and communication
      strategies used with hormone therapy may be applicable to other efforts that
      involve working with reporters on major health stories or events. An important
      process oversight was the absence of hormone therapy communication efforts and
      guidance directed specifically to medical practitioners.

PMID- 18083453
TI  - Exposure to environmental tobacco smoke in the nonsmoking population of Cambodia.
AB  - OBJECTIVE: To estimate the extent of environmental tobacco smoke (ETS) exposure
      among nonsmokers in the adult population of Cambodia. METHODS: A cross-sectional
      survey was conducted on a nationally representative sample of 13,988 Cambodian
      adults in 2005. Information on smoking and exposure to ETS was obtained by
      trained interviewers using a standard questionnaire. RESULTS: Overall, 37.4% of
      the 10,263 nonsmoking responders, or an estimated 1,629,700 nonsmoking
      Cambodians, were exposed to ETS. One third of pregnant women (31.4%) were exposed
      to ETS at home. In both unadjusted and adjusted models, men were less likely to
      be exposed to ETS at home (OR=0.34; 95% CI=0.29-0.41) and more likely to be
      exposed to ETS at work and in public places (OR=3.08; 95% CI=2.14-4.43 and
      OR=2.17; 95% CI=1.82-2.59, respectively). Education was inversely related to ETS
      exposure at home (OR=0.51; 95% CI=0.27-0.96 for 10 years of education vs 5 years
      or less). Legislators, senior officials, and managers were less likely to be
      exposed to ETS at home than professionals (OR=0.13; 95% CI=0.04-0.46), but more
      likely to be exposed at work or in public places. Rural residence was associated
      with higher ETS exposure in the home (OR=2.52; 95% CI=1.71-3.71) and lower ETS
      exposure at work (OR=0.42; 95% CI=0.24-0.76) compared to urban residence.
      CONCLUSIONS: The high prevalence of ETS exposure among adult Cambodians indicates
      an urgent need for specific measures such as public awareness campaigns,
      policies, and regulations to protect nonsmokers in Cambodia.

PMID- 18083454
TI  - Playing for real: video games and stories for health-related behavior change.
AB  - BACKGROUND: Video games provide extensive player involvement for large numbers of
      children and adults, and thereby provide a channel for delivering health behavior
      change experiences and messages in an engaging and entertaining format. METHOD:
      Twenty-seven articles were identified on 25 video games that promoted health
      related behavior change through December 2006. RESULTS: Most of the articles
      demonstrated positive health-related changes from playing the video games.
      Variability in what was reported about the games and measures employed precluded
      systematically relating characteristics of the games to outcomes. Many of these
      games merged the immersive, attention-maintaining properties of stories and
      fantasy, the engaging properties of interactivity, and behavior-change technology
      (e.g., tailored messages, goal setting). Stories in video games allow for
      modeling, vicarious identifying experiences, and learning a story's "moral,"
      among other change possibilities. CONCLUSIONS: Research is needed on the optimal
      use of game-based stories, fantasy, interactivity, and behavior change technology
      in promoting health-related behavior change.

PMID- 18083455
TI  - Medicine and media: state of the union?

PMID- 18083456
TI  - Improvements in short-form measures of health status: introduction to a series.

PMID- 18083457
TI  - Searching PsycINFO just got easier.

PMID- 18083458
TI  - Training improves agreement among doctors using the Neer system for proximal
      humeral fractures in a systematic review.
AB  - OBJECTIVE: To systematically review studies of observer agreement among doctors
      classifying proximal humeral fractures according to the Neer system. STUDY DESIGN
      AND SETTING: A systematic review. We searched for observational studies in which
      doctors classified proximal humeral fractures according to the Neer system, and
      randomized trials of any intervention aimed at improving agreement. We analyzed
      potential eligible studies independently, and data were extracted using pretested
      forms. Authors were contacted for missing information. Summary statistics for
      observer agreement were noted, and the methodological quality was assessed.
      RESULTS: We included 11 observational studies (88 observers and 468 cases). Mean
      kappa-values for interobserver agreement ranged from 0.17 to 0.52. Agreement did
      not improve through selection of experienced observers, advanced imaging
      modalities, or simplification of the classification system. Intra-observer
      agreement was moderately higher than interobserver agreement. One randomized
      trial (14 observers and 42 cases) reported a clear effect of training (mean kappa
      value 0.62 after training compared to no training 0.34). CONCLUSION: We found a
      consistently low level of observer agreement. The widely held belief that experts
      disagree less than nonexperts could not be supported. One randomized trial
      indicated that training improves agreement among both experts and nonexperts.

PMID- 18083459
TI  - Evaluation of a preliminary physical function item bank supported the expected
      advantages of the Patient-Reported Outcomes Measurement Information System
      (PROMIS).
AB  - OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS)
      was initiated to improve precision, reduce respondent burden, and enhance the
      comparability of health outcomes measures. We used item response theory (IRT) to
      construct and evaluate a preliminary item bank for physical function assuming
      four subdomains. STUDY DESIGN AND SETTING: Data from seven samples (N=17,726)
      using 136 items from nine questionnaires were evaluated. A generalized partial
      credit model was used to estimate item parameters, which were normed to a mean of
      50 (SD=10) in the US population. Item bank properties were evaluated through
      Computerized Adaptive Test (CAT) simulations. RESULTS: IRT requirements were
      fulfilled by 70 items covering activities of daily living, lower extremity, and
      central body functions. The original item context partly affected parameter
      stability. Items on upper body function, and need for aid or devices did not fit
      the IRT model. In simulations, a 10-item CAT eliminated floor and decreased
      ceiling effects, achieving a small standard error (< 2.2) across scores from 20
      to 50 (reliability >0.95 for a representative US sample). This precision was not
      achieved over a similar range by any comparable fixed length item sets.
      CONCLUSION: The methods of the PROMIS project are likely to substantially improve
      measures of physical function and to increase the efficiency of their
      administration using CAT.

PMID- 18083460
TI  - PsycINFO search strategies identified methodologically sound therapy studies and
      review articles for use by clinicians and researchers.
AB  - OBJECTIVE: This study evaluated search strategies for finding high-quality
      studies on treatment and systematic reviews in PsycINFO. STUDY DESIGN AND
      SETTING: Sixty-four journals were hand searched at McMaster University.
      Methodologic criteria were applied to clinically relevant articles to identify
      "pass" and "fail" articles; 4,985 candidate terms were compiled, 7,463
      combinations for therapy articles, and 5,246 combinations for reviews. Candidate
      search strategy results were compared with hand searches. The proposed strategies
      served as "diagnostic tests" for sound studies; the hand searches were the "gold
      standard." Sensitivity, specificity, precision, and accuracy were calculated.
      RESULTS: Of 716 treatment articles, 233 (32.5%) met criteria for scientific
      merit, and 58 (11.5%) of 506 review articles met criteria for systematic reviews.
      For treatment studies, combined terms had a peak sensitivity of 97.9%
      (specificity 52.2%). Maximum specificity was 97.7% (sensitivity 51.5%).
      Sensitivity and specificity were each 79% when optimizing both while minimizing
      their difference. For review articles, combined terms had a peak sensitivity of
      81.0% (specificity 54.4%). Maximum specificity was 98.1% (sensitivity 51.7%).
      Sensitivity and specificity were each 65% when optimizing both while minimizing
      their difference. CONCLUSIONS: Empirically derived search strategies can achieve
      high sensitivity and specificity for retrieving sound treatment studies and
      review articles from PsycINFO.

PMID- 18083461
TI  - The binomial distribution of meta-analysis was preferred to model within-study
      variability.
AB  - OBJECTIVE: When studies report proportions such as sensitivity or specificity, it
      is customary to meta-analyze them using the DerSimonian and Laird random effects
      model. This method approximates the within-study variability of the proportion by
      a normal distribution, which may lead to bias for several reasons. Alternatively
      an exact likelihood approach based on the binomial within-study distribution can
      be used. This method can easily be performed in standard statistical packages. We
      investigate the performance of the standard method and the alternative approach.
      STUDY DESIGN AND SETTING: We compare the two approaches through a simulation
      study, in terms of bias, mean-squared error, and coverage probabilities. We
      varied the size of the overall sensitivity or specificity, the between-studies
      variance, the within-study sample sizes, and the number of studies. The methods
      are illustrated using a published meta-analysis data set. RESULTS: The exact
      likelihood approach performs always better than the approximate approach and
      gives unbiased estimates. The coverage probability, in particular for the profile
      likelihood, is also reasonably acceptable. In contrast, the approximate approach
      gives huge bias with very poor coverage probability in many cases. CONCLUSION:
      The exact likelihood approach is the method of preference and should be used
      whenever feasible.

PMID- 18083462
TI  - Three methods to construct predictive models using logistic regression and
      likelihood ratios to facilitate adjustment for pretest probability give similar
      results.
AB  - OBJECTIVE: To compare three predictive models based on logistic regression to
      estimate adjusted likelihood ratios allowing for interdependency between
      diagnostic variables (tests). STUDY DESIGN AND SETTING: This study was a review
      of the theoretical basis, assumptions, and limitations of published models; and a
      statistical extension of methods and application to a case study of the diagnosis
      of obstructive airways disease based on history and clinical examination.
      RESULTS: Albert's method includes an offset term to estimate an adjusted
      likelihood ratio for combinations of tests. Spiegelhalter and Knill-Jones method
      uses the unadjusted likelihood ratio for each test as a predictor and computes
      shrinkage factors to allow for interdependence. Knottnerus' method differs from
      the other methods because it requires sequencing of tests, which limits its
      application to situations where there are few tests and substantial data.
      Although parameter estimates differed between the models, predicted "posttest"
      probabilities were generally similar. CONCLUSION: Construction of predictive
      models using logistic regression is preferred to the independence Bayes' approach
      when it is important to adjust for dependency of tests errors. Methods to
      estimate adjusted likelihood ratios from predictive models should be considered
      in preference to a standard logistic regression model to facilitate ease of
      interpretation and application. Albert's method provides the most straightforward
      approach.

PMID- 18083463
TI  - Trial sequential analysis may establish when firm evidence is reached in
      cumulative meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Cumulative meta-analyses are prone to produce spurious
      P<0.05 because of repeated testing of significance as trial data accumulate.
      Information size in a meta-analysis should at least equal the sample size of an
      adequately powered trial. Trial sequential analysis (TSA) corresponds to group
      sequential analysis of a single trial and may be applied to meta-analysis to
      evaluate the evidence. STUDY DESIGN AND SETTING: Six randomly selected neonatal
      meta-analyses with at least five trials reporting a binary outcome were examined.
      Low-bias heterogeneity-adjusted information size and information size determined
      from an assumed intervention effect of 15% were calculated. These were used for
      constructing trial sequential monitoring boundaries. We assessed the cumulative z
      curves' crossing of P=0.05 and the boundaries. RESULTS: Five meta-analyses showed
      early potentially spurious P<0.05 values. In three significant meta-analyses the
      cumulative z-curves crossed both boundaries, establishing firm evidence of an
      intervention effect. In two nonsignificant meta-analyses the cumulative z-curves
      crossed P=0.05, but never the boundaries, demonstrating early potentially
      spurious P<0.05 values. In one nonsignificant meta-analysis the cumulative z
      curves never crossed P=0.05 or the boundaries. CONCLUSION: TSAs may establish
      when firm evidence is reached in meta-analysis.

PMID- 18083464
TI  - Updating methods improved the performance of a clinical prediction model in new
      patients.
AB  - OBJECTIVE: Ideally, clinical prediction models are generalizable to other patient
      groups. Unfortunately, they perform regularly worse when validated in new
      patients and are then often redeveloped. While the original prediction model
      usually has been developed on a large data set, redevelopment then often occurs
      on the smaller validation set. Recently, methods to update existing prediction
      models with the data of new patients have been proposed. We used an existing
      model that preoperatively predicts the risk of severe postoperative pain (SPP) to
      compare five updating methods. STUDY DESIGN AND SETTING: The model was tested and
      updated with a set of 752 new patients (274 [36] with SPP). We studied the
      discrimination (ability to distinguish between patients with and without SPP) and
      calibration (agreement between the predicted risks and observed frequencies of
      SPP) of the five updated models in 283 other patients (100 [35%] with SPP).
      RESULTS: Simple recalibration methods improved the calibration to a similar
      extent as revision methods that made more extensive adjustments to the original
      model. Discrimination could not be improved by any of the methods. CONCLUSION:
      When the performance is poor in new patients, updating methods can be applied to
      adjust the model, rather than to develop a new model.

PMID- 18083465
TI  - Unmeasured confounding caused slightly better response to HAART within than
      outside a randomized controlled trial.
AB  - OBJECTIVE: To compare the outcome of highly active antiretroviral therapy (HAART)
      in HIV-infected patients initiating equivalent regimens within and outside a
      randomized controlled trial (RCT). STUDY DESIGN AND SETTING: The Danish Protease
      Inhibitor Study (DAPIS) was a national multicenter RCT comparing initial
      treatment with indinavir, ritonavir, or saquinavir/ritonavir during 96 weeks.
      From the Danish HIV Cohort Study we identified all patients initiating one of
      these protease-inhibitor-based HAART regimens: 425 patients within DAPIS and 677
      outside the trial. We compared viral load, CD4 count response, and mortality.
      RESULTS: At weeks 96 and 240, trial participants were more likely than
      nonparticipants to have undetectable viral load (adjusted odds ratio [adOR] 1.28
      [95% CI=0.94-1.74] and 1.70 [95% CI=1.16-2.50]) and a CD4 increase > or =100
      cells/microl (adOR 1.37 [95% CI=1.03-1.82] and 1.53 [95% CI=1.04-2.25]). For
      antiretroviral-experienced, but not for antiretroviral-naive patients, trial
      participants had a lower risk of death (mortality rate ratio [MRR]=0.46 [95%
      CI=0.27-0.77]) than nonparticipants. This effect was moderated in adjusted
      analyses (MRR=0.60 [0.33-1.07]). CONCLUSIONS: Compared to nontrial patients,
      trial participants had better response to HAART. The differences were small
      defying the notion that results obtained in RCTs are unachievable in routine
      clinical practice.

PMID- 18083466
TI  - Systematic reviews are not biased by results from trials stopped early for
      benefit.

PMID- 18083468
TI  - How often should we perform arterial blood gas analysis during thoracoscopic
      surgery?
AB  - STUDY OBJECTIVES: To continuously measure arterial blood gases (ABGs), to
      calculate the percentage of anticipated changes over time, and to develop
      recommendations for sampling frequencies of arterial blood gases in patients
      undergoing thoracoscopic surgery. DESIGN: Prospective, observational clinical
      trial. SETTING: University hospital. PATIENTS: 43 consecutive elective patients
      undergoing thoracoscopic surgery with one-lung ventilation. INTERVENTIONS AND
      MEASUREMENTS: A Paratrend 7 probe for continuous arterial partial pressure of
      oxygen and arterial partial pressure of carbon dioxide measurement was introduced
      through a radial artery cannula in the awake patient before surgery. Data were
      collected throughout the procedure until patients left the operating room.
      Afterward, time courses of arterial blood gas values were transformed into
      frequency space by fast Fourier transform analysis, and the expected deviations
      in arterial blood gases were calculated over time. MAIN RESULTS: Forty-three
      consecutive patients undergoing thoracoscopic surgery were included, and arterial
      blood gas values were measured during a total of 141.5 h. Critical arterial
      partial pressure of oxygen values <or=60 mmHg were recorded in 16 patients for a
      total of 4.5 hours. Fourier amplitude spectra showed comparable characteristics
      of arterial partial pressure of oxygen and arterial partial pressure of carbon
      dioxide time courses in all patients. It takes only 5, 10, or 20 minutes for the
      arterial partial pressure of oxygen to change 10%, 20%, or 40%, respectively (95%
      confidence). CONCLUSIONS: Current standards to monitor arterial blood gases are
      not sufficient to detect and prevent hypoxemic events during thoracoscopic
      surgery with one-lung ventilation. Intermittent arterial blood gas analyses must
      be performed more frequently, up to every 10 minutes, to detect changes of 20% in
      arterial partial pressure of oxygen.

PMID- 18083470
TI  - Teaching without a teacher: developing competence with a Bullard laryngoscope
      using only a structured self-learning course and practicing on a mannequin.
AB  - STUDY OBJECTIVE: To show that a complex motor skill can be taught without
      requiring active expert faculty participation. DESIGN: Prospective descriptive
      study. SETTING: Simulation laboratory of an academic anesthesiology department.
      SUBJECTS: Novice users of the Bullard laryngoscope, predominantly residents.
      INTERVENTIONS: Novice Bullard users were presented with a PowerPoint presentation
      using text and pictures describing the use of the Bullard. The learners were also
      provided with a Bullard laryngoscope and a mannequin on which to practice. Self
      learning time was not restricted. MEASUREMENTS: Learners decided for themselves
      when they were competent and ready for competency assessment. The assessment tool
      was a checklist of essential steps developed by faculty experienced in Bullard
      laryngoscopy. The primary end-point was successful intubation. MAIN RESULTS: All
      learners were deemed competent. The mean self-learning time was 14.1 minutes (SD,
      3.1 min; range, 9.2-21.0 min). All subjects indicated a high level of
      satisfaction with the learning technique. CONCLUSIONS: Teaching a complex motor
      skill with no expert instruction is possible.

PMID- 18083469
TI  - Clinical analgesic efficacy and side effects of dexmedetomidine in the early
      postoperative period after arthroscopic knee surgery.
AB  - STUDY OBJECTIVES: To determine the analgesic efficacy of dexmedetomidine in the
      early postoperative period. DESIGN: Randomized, double-blind, double placebo
      controlled clinical trial. SETTING: University medical center. PATIENTS: 30 ASA
      physical status I, II, and III patients with cruciate ligament lesion and joint
      fibrosis who were scheduled for knee arthroscopy. INTERVENTIONS: Patients were
      prospectively randomized to receive dexmedetomidine one mcg/kg(-1) intravenously
      (IV), for 10 minutes followed by dexmedetomidine 0.3 mcg/kg(-1) for 50 minutes or
      propacetamol two g, IV, for 10 minutes. MEASUREMENTS: Pain scores, time to onset
      analgesia, and morphine consumption were measured. Open-label rescue morphine 5
      mg IV was available as needed during the postdosing evaluation period of 8 hours.
      Hemodynamic data, sedation scores, and renal and hepatic function were assessed
      for control of adverse events. MAIN RESULTS: Pain scores with dexmedetomidine and
      propacetamol were similar. There were no differences in the number of patients
      who required supplemental rescue analgesia (7/15 vs 4/15; P = 0.44), but total
      morphine requirements were higher with dexmedetomidine (45 mg) versus
      propacetamol (20 mg) in the 8-hour follow-up (P < 0.05). The most frequent
      adverse events with dexmedetomidine were bradycardia and hypertension.
      CONCLUSIONS: Dexmedetomidine provides a modest analgesic effect after knee
      arthroscopy, but the side effects of this drug, such as hypertension and
      bradycardia, may restrict the use of large bolus doses.

PMID- 18083471
TI  - The analgesic efficacy of preoperative versus postoperative lornoxicam in
      varicocele repair.
AB  - STUDY OBJECTIVE: To determine whether intravenous injection of lornoxicam 30
      minutes before skin incision provides better pain relief after varicocelectomy
      than postoperative administration of lornoxicam. DESIGN: Prospective, double
      blind, randomized clinical investigation. SETTING: Operating room and
      postoperative recovery area. PATIENTS: 44 ASA physical status I and II adult male
      patients undergoing varicocelectomy. INTERVENTIONS: Patients were randomized
      either to receive 8 mg lornoxicam infusion 30 minutes before skin incision,
      followed by saline infusion immediately after skin closure (group 1), or to
      receive the identical injections but in reverse order (group 2). All patients
      received local anesthesia with bupivacaine. MEASUREMENTS: Postoperative pain
      scores were evaluated hourly for the first 8 hours after surgery, then at 12, 16,
      20, and 24 hours after surgery, using a 10-cm visual analog scale. Time to first
      analgesic request and patients' global assessments also were recorded. MAIN
      RESULTS: Patients in group 1 reported significantly lower pain scores (P < 0.05)
      at all time intervals except at 24 hours and better global assessment (P = 0.001)
      than did group 2. There were significantly fewer patients in the preemptive group
      than group 2 who required rescue analgesic within the first 24 hours (0% vs
      22.7%; P = 0.024). Mean time to first analgesic request was also significantly
      longer in the preemptive group (P = 0.001). CONCLUSION: Intravenous lornoxicam
      administered before surgery has a better analgesic effect for varicocelectomy
      than when administered postoperatively.

PMID- 18083473
TI  - Preoperative flurbiprofen for pain prevention after tonsillectomy in adults.
AB  - STUDY OBJECTIVE: To investigate the analgesic efficacy of preoperative
      flurbiprofen on postoperative pain after tonsillectomy. DESIGN: Prospective,
      randomized, nonblinded, non-placebo-controlled study. SETTING: Municipal
      hospital. PATIENTS: Twenty-five ASA physical status I patients older than 20
      years of age, who were scheduled for tonsillectomy. INTERVENTIONS: Patients were
      randomly allocated to two groups to receive preoperative intravenous (IV) 50 mg
      flurbiprofen (group F) or not (group C). Anesthesia was induced with IV propofol
      two mg/kg and maintained with nitrous oxide and sevoflurane. MEASUREMENTS: Pain
      scores at rest and at swallowing, intraoperative bleeding, vital signs during the
      postanesthetic period, interval until diclofenac sodium suppository rescue, and
      the total dose required for 12 hours postoperatively were all recorded. MAIN
      RESULTS: Pain scores at rest as well as those recorded after swallowing 30
      minutes after tonsillectomy were significantly lower in group F than in group C.
      During the first postoperative 1.5 hours, significantly fewer patients in group F
      required rescue diclofenac suppository than did group C patients. However, total
      dose of required rescue during the postoperative 12 hours in group F did not
      significantly differ from that of group C. There were no significant differences
      in intraoperative bleeding or in any vital signs during the postanesthetic period
      either. CONCLUSION: Preoperative flurbiprofen suppressed immediate postoperative
      pain after tonsillectomy. The analgesic effect, however, disappeared in a few
      hours and was insufficient for overnight pain relief.

PMID- 18083472
TI  - Comparison of sciatic psoas compartment block and sciatic femoral 3-in-1 block
      for knee arthroscopy.
AB  - STUDY OBJECTIVES: To compare the clinical effectiveness of two peripheral nerve
      block techniques combined with sciatic nerve block: sciatic psoas compartment
      (SPC) and sciatic femoral 3-in-1 (SF 3-in-1) block. DESIGN: Prospective,
      randomized study. SETTING: Military medical academy hospital. PATIENTS: Thirty
      six ASA physical status I patients, aged 20 to 33 years, undergoing elective knee
      arthroscopy. INTERVENTIONS: Patients having SPC block (n = 19) or SF 3-in-1 block
      (n = 17) received 40 mL of a mixture of solution containing 15 mL of 0.5%
      bupivacaine, 15 mL of 2.0% prilocaine, and 10 mL of 0.9% sodium chloride. In both
      groups, the sciatic nerve was blocked with 20 mL of the same solution. An
      intravenous bolus injection of fentanyl 0.1 mg was used if patients complained of
      pain. MEASUREMENTS AND MAIN RESULTS: None of the patients in the SPC group
      experienced pain owing to the applied tourniquet during the operation, whereas 7
      patients from the SF 3-in-1 group (41.2 %) reported tourniquet pain. All SF 3-in
      1 group patients but only 5 patients (26.3 %) in the SPC group required fentanyl
      during the operation. In addition, 7 patients in the SF 3-in-1 group required
      second doses of fentanyl. Patient satisfaction was significantly higher in the
      SPC group than in the SF 3-in-1 block group (P < 0.0001). CONCLUSIONS: Both SPC
      and SF 3-in-1 provided sufficient anesthetic efficacy for knee arthroscopy.
      However, SPC may be preferable to SF 3-in-1 block owing to better patient
      satisfaction and less requirement for opioid analgesics.

PMID- 18083475
TI  - Experience of anesthesiologists with percutaneous nonangiographic venous access.
AB  - STUDY OBJECTIVE: To compare percutaneous nonangiographic insertion of a venous
      access device with a standard surgical cutdown insertion technique. DESIGN:
      Prospective, controlled, randomized study. SETTING: Operating room and anesthesia
      induction room of a university hospital. PATIENTS: 100 consecutive oncology
      patients scheduled for intravenous chemotherapy. INTERVENTIONS: Patients were
      randomized to two groups: (1) The percutaneous group received implantation
      through the internal jugular vein by experienced anesthesiologists, whereas (2)
      the surgical group received venous cutdown insertion through the cephalic or
      subclavian vein by surgeons (n = 50 for each group). MEASUREMENTS: Duration of
      procedure, long-term device function, complications such as hematoma formation,
      infection, hemothorax, pneumothorax, and patients' satisfaction with the
      placement procedure at two months of follow-up were all measured and recorded.
      MAIN RESULTS: The percutaneous technique was found to have several advantages,
      including reduced time for insertion and greater patient satisfaction with
      procedure. The percutaneously implanted devices also had fewer insertion
      associated complications. CONCLUSION: The simplified, percutaneous,
      nonangiographic technique is as effective as the traditional venous cutdown
      technique and can be safely done by surgeons as well as by experienced physicians
      who are not surgeons.

PMID- 18083474
TI  - How much are patients willing to pay to avoid postoperative muscle pain
      associated with succinylcholine?
AB  - STUDY OBJECTIVE: To determine how much money patients are willing to pay to avoid
      postoperative muscle pains associated with succinylcholine. DESIGN: Observational
      study with survey instrument. SETTING: University-affiliated metropolitan
      hospital. PATIENTS: Eighty-eight adult patients, 43 men and 45 women, who were
      scheduled to undergo surgery with general anesthesia and who completed a
      preoperative questionnaire (median age range, 41-50 y; median income, US$45,000
      60,000). INTERVENTIONS AND MEASUREMENTS: Patients completed a computerized,
      interactive questionnaire preoperatively. They were asked about demographics and
      previous experiences with muscle pain and postoperative myalgia. With the use of
      the willingness-to-pay model, the value that they would be willing to pay for a
      hypothetical muscle relaxant that avoided postoperative myalgia was determined.
      MAIN RESULTS: Eighty-nine percent of patients considered avoiding postoperative
      myalgia as important. Patients were willing to pay a median (interquartile range)
      of $33 ($19-$50) out of pocket for a muscle relaxant that was not associated with
      postoperative myalgia, a figure that increased to $40 if the insurance company
      paid for the drug (P < 0.0001). Willingness to pay was influenced by patients'
      income but not by prior experience with postoperative myalgia. CONCLUSION:
      Patients consider avoidance of postoperative myalgia important and are willing to
      pay $33 out of pocket for a muscle relaxant that is not associated with this side
      effect.

PMID- 18083476
TI  - Special anesthetic considerations for stereotactic radiosurgery in children.
AB  - Children present special anesthetic considerations, not only in their unique
      pharmacologic and physiologic attributes but also in the types of anesthetic care
      they require. A new neurosurgical technique, the gamma knife, is particularly
      challenging for pediatric anesthesia providers because of its extended duration,
      multiple site procedures, and anesthetic requirements associated with the use of
      a stereotactic frame.

PMID- 18083477
TI  - Soft palate perforation during orotracheal intubation facilitated by the
      GlideScope videolaryngoscope.
AB  - We report a case in which a videolaryngoscope was used to facilitate endotracheal
      intubation in a patient with a large exophytic mass involving the right
      supraglottis. After intubation, it was noted that the soft palate had been
      perforated by the styletted endotracheal tube. The defect closed spontaneously
      postoperatively within 9 days.

PMID- 18083478
TI  - Dolasetron-induced torsades de pointes.
AB  - A 52-year-old woman with hypertension and Graves' disease was scheduled for
      surgical removal of a meningioma. Intraoperative events were significant for
      hypotension requiring a vasopressin infusion. Prophylactic dolasetron was
      administered to the patient before emergence. The patient's trachea was easily
      extubated and she was neurologically intact at the end of the surgical procedure.
      On transport to the neurological intensive care unit, the patient developed
      torsades de pointes, requiring cardiopulmonary resuscitation, before a return to
      normal sinus rhythm.

PMID- 18083479
TI  - Ultrasound-guided sciatic neuroma block for treatment of intractable stump pain.
AB  - A 61-year-old patient with severe stump pain required hospitalization and
      intravenous opioids for pain control. After evaluation by our anesthesia pain
      management service, we concluded that the patient had a neuroma at the site of
      sciatic nerve transection and that injection of a mixture of local anesthetic and
      corticosteroid at the site of the neuroma was the most appropriate management.
      Because the alternative methods of nerve localization (eg, motor stimulation,
      paresthesia) were unlikely to be successful, we felt that the most reliable way
      to accomplish this task was to use live ultrasound guidance. After a series of 4
      ultrasound-guided blocks with bupivacaine and methylprednisolone acetate, the
      patient's pain was alleviated to the point at which it was managed with
      occasional doses of oral opioids.

PMID- 18083480
TI  - Successful airway management of a patient with a known difficult airway with the
      Direct Coupler Interface Video Laryngoscope.
AB  - We present the case of a patient who first presented with unexpected difficult
      laryngoscopy and intubation after induction of general anesthesia. After multiple
      failed attempts using direct laryngoscopy, tracheal intubation was successfully
      performed with the Intubating Laryngeal Mask Airway. He returned to the operating
      room 5 days later for another surgical procedure, and intubation was performed
      with the Direct Coupler Interface Video Laryngoscope on the first attempt by the
      same anesthesiologist.

PMID- 18083481
TI  - Occurrence of pneumothorax during noninvasive positive pressure ventilation
      through a helmet.
AB  - A 79-year-old woman presented with hypoxemic acute respiratory failure secondary
      to pneumonia and was started on continuous noninvasive positive pressure
      ventilation (NPPV) by helmet. Patient improved over first two days of NPPV, but
      worsened suddenly on the third day because of development of a pneumothorax.
      Pneumothorax may have been caused by barotrauma from desynchronization between
      patient and ventilator.

PMID- 18083482
TI  - Posterior shoulder subluxation most likely caused by retching in the lateral head
      down position for prevention of aspiration.
AB  - A patient who sustained a posterior shoulder subluxation injury after being
      positioned in the lateral decubitus head-down position during emergence from
      general anesthesia is presented. It is postulated that the injury occurred as a
      result of violent retching while in the lateral position.

PMID- 18083483
TI  - To tell the truth: potential liability for concealing physician impairment.

PMID- 18083485
TI  - Pentax-AWS (Airway Scope) for awake tracheal intubation.

PMID- 18083486
TI  - Re: Anesthesia awareness: an analysis of its incidence, the risk factors
      involved, and prevention.

PMID- 18083487
TI  - Innovative uses of dexmedetomidine.

PMID- 18083488
TI  - Horner syndrome can be clinically important.

PMID- 18083489
TI  - A novel method of labeling drug syringes.

PMID- 18083492
TI  - Contribution of cortical and subcortical electrostimulation in brain glioma
      surgery: methodological and functional considerations.
AB  - The aim of brain glioma surgery is to maximize the quality of resection, while
      minimizing the risk of sequelae. Due to the frequent location of gliomas in
      "eloquent areas" and because of major interindividual anatomofunctional
      variability, the cortical functional organization, effective connectivity and
      potential for plasticity must be studied for each patient individually.
      Consequently, in addition to preoperative functional neuroimaging, intraoperative
      electrostimulation (IES) can be used, under general anesthesia for motor mapping
      or on awake patient for language and cognitive mapping. This is an easy,
      accurate, reliable, and safe technique of detection of both cortical and
      subcortical functionally essential structures. Thus, IES enables: (i) to study
      the individual cortical functional organization before any resection; (ii) to
      understand the pathophysiology of areas involved by gliomas; (iii) to map the
      subcortical structures along the resection, allowing a study of the
      anatomofunctional connectivity; (iv) to analyze the mechanisms of on-line short
      term plasticity, using repeated IES; (v) to tailor the resection according to
      individual cortico-subcortical functional boundaries, enabling to optimize the
      benefit:risk ratio of surgery. Moreover, IES can be combined with perioperative
      functional neuroimaging, before and after surgery, to validate these noninvasive
      techniques and to better understand the short-term and long-term plasticity
      mechanisms based on functional cortical reshaping and connectivity changes. Such
      individual knowledge allows planning multiple-stages surgery. In conclusion, IES
      enables to increase the impact of surgery on the natural history of gliomas, to
      preserve the quality of life, and to better understand the dynamic functional
      anatomy of the brain.

PMID- 18083493
TI  - Stroke prevention during surgery for deep-seated gliomas.
AB  - AIMS OF THE STUDY: New motor deficit after surgery for deep-seated gliomas can
      occur from subcortical ischemia of the pyramidal tract. Motor evoked potentials
      (MEPs) validly indicate impending motor tract ischemia in cerebrovascular
      surgery. This study determines the feasibility and clinical utility of MEP
      monitoring for ischemic complication avoidance during surgery for deep-seated,
      specifically insular gliomas. METHODS: MEPs were recorded during 100 operations
      of insular gliomas. Intraoperative MEP results were correlated with postoperative
      clinical and imaging results. RESULTS: Useful MEP monitoring was possible in
      89/100 cases, 88 of which were assessable since one patient died early
      postoperatively. Stable recordings warranted unimpaired motor outcome in 47/88
      cases (53%). Surgical intervention reversed MEP attenuation in 26 of the
      remaining 41 cases (30% of the overall series) to prevent motor deficit except
      transient paresis in 12 (14%). Irreversible MEP changes without loss in eight
      cases (9%) resulted in only transient new deficit in seven cases, except one with
      permanent new paresis. Permanent paresis also occurred in seven cases (8%) where
      complete MEP loss could not be prevented. Permanent paresis arose exclusively
      through stroke of the deep motor pathways, whereas transient deficit typically
      corresponded to transitory ischemia of the pyramidal tract. MEP changes
      attributable to ischemic events frequently occurred spatially and temporally
      uncorrelated to resection in critical proximity of the motor tract. CONCLUSIONS:
      Ischemia in deep-seated glioma surgery usually occurs uncorrelated to resection
      close to the pyramidal tract. MEP monitoring efficiently helps detect ischemia
      early and to avert definite stroke and permanent new paresis in part of these
      cases.

PMID- 18083494
TI  - Transcranial and direct cortical stimulation for motor evoked potential
      monitoring in intracerebral aneurysm surgery.
AB  - STUDY AIM: To analyse the parallel use of transcranial electrical stimulation
      (TES) and direct cortical stimulation (DCS) for eliciting muscle motor evoked
      potentials (MMEPs) in intracranial aneurysm surgery; to correlate permanent or
      transient TES- and/or DCS-MMEP changes with surgical maneuvers and clinical motor
      outcome. PATIENTS AND METHODS: TES and DCS were intraoperatively performed in 108
      patients (51.5+/-14.7 years); MMEPs were obtained in muscles belonging to the
      vascular territory of interest. Monopolar, anodal stimulation was achieved with a
      train of five stimuli consisting of an individual pulse width of 0.5ms, an
      interstimulus interval of 4ms, a train repetition rate of 0.5-2Hz, and maximum
      stimulation intensities up to 200mA (TES) versus 25mA (DCS). RESULTS: In 95/108
      (88%) patients, no changes in MMEPs occurred and none of these patients suffered
      a permanent severe motor deficit. In 14/108 (12%) patients, we observed nine
      (64%) temporary changes, four (29%) permanent deteriorations and one (7%)
      permanent MMEP loss. Out of 14 MMEP changes, nine (64%) occurred with TES,
      compared to 13 (93%) with DCS (Fishers'p=0.165). Parallel changes in TES- and DCS
      MMEPs occurred in 8/14 patients (57%), in which case a permanent loss was always
      followed by a permanent severe motor deficit. Sixty-seven percent of all
      permanent changes occurred with DCS-MMEPs, compared to 33% with TES-MMEPs
      (p=0.567, NS). DISCUSSION AND CONCLUSIONS: In aneurysm surgery, provided that
      close-to-motor-threshold stimulation and the most focal stimulating electrode
      montage are used, TES- and DCS-MMEPs do not differ in their capacity to detect an
      impending lesion of the motor cortex or its efferent pathways. TES stimulation
      can cause significant muscular contraction during surgery, potentially disrupting
      the operating surgeon. DCS maintains the singular advantage of stimulating a very
      focal and superficial motor cortex stimulation that does not result in patient
      movement.

PMID- 18083495
TI  - Monitoring of motor pathways during brain stem surgery: what we have achieved and
      what we still miss?
AB  - Intraoperative neurophysiological monitoring (IOM) has established itself as one
      of the paths by which modern neurosurgery can improve surgical results while
      minimizing morbidity. IOM consists of both monitoring (continuous "on-line"
      assessment of the functional integrity of neural pathways) and mapping
      (functional identification and preservation of anatomically ambiguous nervous
      tissue) techniques. In posterior-fossa and brainstem surgery, mapping techniques
      can be used to identify - and therefore preserve - cranial nerves, their motor
      nuclei and corticospinal or corticobulbar pathways. Similarly, free-running
      electromyography (EMG) and muscle motor-evoked potential (mMEP) monitoring can
      continuously assess the functional integrity of these pathways during surgery.
      Mapping of the corticospinal tract, at the level of the cerebral peduncle as well
      as mapping of the VII, IX-X and XII cranial nerve motor nuclei on the floor of
      the fourth ventricle, is of great value to identify "safe entry-zones" into the
      brainstem. Mapping techniques allow recognizing anatomical landmarks such as the
      facial colliculus, the hypoglosseal and glossopharyngeal triangles on the floor
      of the fourth ventricle, even when normal anatomy is distorted by a tumor. On the
      basis of neurophysiological mapping, specific patterns of motor cranial nuclei
      displacement can be recognized. However, brainstem mapping cannot detect injury
      to the supranuclear tracts originating in the motor cortex and ending on the
      cranial nerve motor nuclei. Therefore, monitoring techniques should be used.
      Standard techniques for continuously assessing the functional integrity of motor
      cranial nerves traditionally rely on the evaluation of spontaneous free-running
      EMG in muscles innervated by motor cranial nerves. Although several criteria have
      been proposed to identify those EMG activity patterns that are suspicious for
      nerve injury, the terminology remains somewhat confusing and convincing data
      regarding a clinical correlation between EMG activity and clinical outcome are
      still lacking. Transcranial mMEPs are also currently used during posterior-fossa
      surgery and principles of MEP monitoring to assess the functional integrity of
      motor pathways are similar to those used in brain and spinal-cord surgery.
      Recently, current concepts in muscle MEP monitoring have been extended to the
      monitoring of motor cranial nerves. So-called "corticobulbar mMEPs" can be used
      to monitor the functional integrity of corticobulbar tracts from the cortex
      through the cranial motor nuclei and to the muscle innervated by cranial nerves.
      Methodology for this purpose has appeared in the literature only recently and
      mostly with regards to the VII cranial nerve monitoring. Nevertheless, this
      technique has not yet been standardized and some limitations still exist. In
      particular, with regards to the preservation of the swallowing and coughing
      reflexes, available intraoperative techniques are insufficient to provide
      reliable prognostic data since only the efferent arc of the reflex can be tested.

PMID- 18083496
TI  - Intraoperative neurophysiologic monitoring for intramedullary spinal-cord tumor
      surgery.
AB  - During resection of intramedullary spinal-cord tumors intraoperative
      neurophysiological monitoring has become a true surgical technology. Motor evoked
      potentials are the most important modality for this purpose. Its use requires
      neurophysiological expertise from the surgeon, and a monitoring team in place
      able to handle the necessary equipment. Motor potentials are evoked by
      transcranial electrical motor cortex stimulation. A "single stimulus technique"
      evokes D-waves recorded from the spinal cord. The "multipulse (or train)
      stimulation technique" evokes electromyographic responses in peripheral muscles.
      These are optimally recorded from the thenar, hypothenar, tibialis anterior, and
      flexor hallucis brevis muscles, which are known to have strong pyramidal
      innervation. D-wave monitoring looks primarily at the peak-to-peak amplitude.
      When monitoring muscle MEPs, the presence or absence of the response irrespective
      of stimulation intensity is the important parameter. Preparations for
      neurophysiological monitoring fit quite well into a neurosurgical operating room
      environment. Recording and interpretation of MEPs is fast and straightforward.
      Pre- and postoperative clinical motor findings correlate with intraoperative MEP
      results. Thus correct prediction of the clinical status at a given time during
      surgery is possible with a very high certainty. The sensitivity of muscle MEPs
      for postoperative motor deficits is nearly 100%, its specificity is about 90%.
      Thus MEP data indeed reflect the clinical "reality". Present and stable
      recordings document intact motor pathways and allow the surgeon to confidently
      proceed with a tumor resection. Loss of muscle MEPs and/or decrease of the D-wave
      amplitude constitutes a "window of warning". It reflects a pattern of MEP change
      indicating a reversible injury to the essential motor pathways. Using this
      information, the surgical strategy can be adapted before irreversible
      neurological damage is caused by the surgical manipulation. Such adaptation
      comprises simply waiting for the recordings to spontaneously improve again,
      irrigating with warm saline solution to wash out blocking potassium. Other
      measures include the elevation of mean arterial pressure to improve local
      perfusion. Even staged resection can be considered if intraoperative measures do
      not sufficiently improve the recordings.

PMID- 18083497
TI  - Neuroprotective role of neurophysiological monitoring during endovascular
      procedures in the brain and spinal cord.
AB  - The goal of endovascular neurosurgery is to occlude aneurysms and arteriovenous
      malformations (AVMs) or to reduce the vascular supply to hypervascularized
      tumors, while preserving function in the normal neural tissue. However, the intra
      arterial injection of embolizing materials into the cerebral or spinal
      circulation exposes to the risk of ischemic complications. Under general
      anesthesia, unless a wake-up test is performed, the only way to assess the
      functional integrity of sensory and motor pathways is to use neurophysiological
      monitoring. Somatosensory (SEPs) and muscle motor evoked potentials (mMEPs) can
      be used in combination with pharmacological provocative tests (PTs) to predict
      the effects of embolization. Amytal blocks neuronal activity, while lidocaine
      blocks axonal conduction. Therefore, a positive Amytal or lidocaine test (i.e.
      more than 50% decrease in SEP amplitude and/or mMEP disappearance) indicates that
      the vessel distal to the tip of the microcatheter supplies the functional gray or
      white matter of the spinal-cord respectively and cannot be embolized. Brain and
      spinal-cord vascularization and hemodynamics are extremely complex and even more
      unpredictable in the presence of a vascular malformation, but using a combined
      SEPs, MEPs and PTs protocol, morbidity related to endovascular procedures is very
      low. Given the high sensitivity of peripheral recordings to spinal-cord ischemia,
      experimental and clinical studies support the concept that whenever the mechanism
      of spinal-cord injury is purely ischemic, recording mMEPs may suffice. Reports on
      the use of PTs and neurophysiological monitoring during embolization of brain
      AVMs in critical areas are more anecdotal and mainly limited to the use of short
      acting barbiturates. Our preliminary experience using lidocaine and combining SEP
      and mMEP monitoring is encouraging, since no false negative results were
      observed. Finally, if the sensitivity of this method is very high, its
      specificity has not been tested because embolization is abandoned whenever PTs
      are consistently positive. Accordingly, the possibility of false positive results
      cannot be excluded.

PMID- 18083498
TI  - Conditioning stimulation techniques for enhancement of transcranially elicited
      evoked motor responses.
AB  - INTRODUCTION: In spite of the use of multipulse, transcranial electrical
      stimulation (TES) is still insufficient in a subgroup of patients to elicit motor
      evoked potentials during intraoperative neurophysiological monitoring (IONM).
      Classic facilitation methods used in awake patients are precluded under general
      anaesthesia. Conditioning techniques can be used in this situation. OBJECTIVE: To
      present clinical experimental data and models of motor-neuron (MN) excitability
      for homonymous and heteronymous conditioning and discuss their applications in
      IONM. MATERIAL AND METHODS: Data were obtained in a prospective study on
      multipulse TES-conditioning of the monosynaptic H-reflex and double multipulse
      TES. DISCUSSION: The principle of facilitation by conditioning stimulation is to
      apply a test stimulus when motor neurons (MNs) have been made maximally excitable
      by a conditioning stimulus. Both conditioning and test stimuli recruit separate
      populations of MNs. The overlapping fraction of MNs controls the efficacy of
      facilitation. Heteronymous conditioning stimulation, which is performed at a
      different site from the test stimulus, is illustrated by the TES-conditioned H
      reflex (HR). Autonomous conditioning stimulation, which is performed at the same
      stimulation site, is illustrated by double-train TES (dt-TES). The facilitating
      curves obtained by conditioning stimulation are often 3-modal and show peaks of
      facilitation at short intertrain intervals (S-ITIs) of 10ms and between 15 and
      20ms and at longer intertrain intervals (L-ITI) of over 100ms. The facilitation
      curves from HR and dt-TES are not always identical since different alphaMN pools
      are involved. Dt-TES is often successful in neurologically impaired patients
      whereas facilitation of the HR can be used when conditioned by TES at
      subthreshold levels allowing continuous IONM without movement in the surgical
      field. Alternatively, facilitation by conditioning from peripheral-nerve
      stimulation can be used for selective transmission of subthreshold TES motor
      responses to peripheral muscles, permitting motor-monitoring by a so-called
      selective motor-gating technique. CONCLUSIONS: Facilitation techniques offer many
      possibilities in IONM by enhancing low-amplitude TES-MEP responses. They can also
      selectively enhance responses in a few muscle groups for the reduction of
      movement.

PMID- 18083499
TI  - Criteria for transcranial electrical motor evoked potential monitoring during
      spinal deformity surgery A review and discussion of the literature.
AB  - Transcranial electrical stimulated motor evoked potential monitoring (TES-MEP)
      has proven to be a successful and reliable neuromonitoring technique during
      spinal correction surgery. However, three criteria for TES-MEP monitoring have
      been described in the literature. This study aims at discussing and comparing the
      following criteria: (1) the "threshold level criterion" introduced by Calancie et
      al. (J Neurosurg 88 (1998) 457-70): a more than 100V over more than 1h increase
      of threshold level to get useful TES-MEP responses indicated neurological
      impairment; (2) the "amplitude criterion": for TES-MEP monitoring in corrective
      surgery of the spine, a more than 80% decrease of one or more response amplitudes
      was considered a valuable criterion for impending neurological deficits by
      Langeloo et al. (Spine 28 (2003) 1043-50); (3) "the morphology criterion":
      introduced in 2005 by Quinones et al. (Neurosurgery 56 (2005) 982-93), it is
      based on the morphology of the MEP-compound muscle action potentials (CMAP). The
      criterion was applied during TES-MEP monitoring during intramedullary spinal cord
      tumour resection. Neurological events are defined by a sharp decrease of response
      duration and/or waveform complexity and an increase in voltage threshold of 100V
      or greater. Although all methods have been reported to be successful during
      spinal surgery, the threshold criterion and the morphology change criterion carry
      several drawbacks. We consider the amplitude reduction method to be most useful
      during corrective spinal surgery. The sequences of observations and decisions
      during a TES-MEP monitoring that is based on this criterion are schematized in a
      flowchart.

PMID- 18083500
TI  - Neurophysiological aspects of chronic motor cortex stimulation.
AB  - Chronic motor cortex stimulation is a treatment option for neuropathic drug
      resistant pain and possibly associated movement disorders. Preliminary studies
      suggest the possibility to treat symptoms of Parkinson disease in selected
      patients. Recently, MCS has been suggested to enhance motor recovery in patients
      with poststroke hemiparesis. One or more electrodes are placed extradurally over
      the motor cortex through a burr hole or a small craniotomy, and then connected to
      a totally implantable neurostimulator. The accurate positioning of the
      stimulating electrodes over the motor cortex is the key point of the surgical
      procedure. Motor cortex identification results from the integration of
      anatomical, neuroradiological, functional, and neurophysiological data, taking
      into account the huge population variability. Intraoperative neurophysiological
      mapping of the motor cortex is of paramount importance, in spite of very
      sophisticated neuroradiological mathematical reconstructions of the motor area.
      We discuss and compare the different techniques that are utilized by different
      authors. Moreover, clinical neurophysiology is also helpful in evaluating the
      results of this neuromodulation procedure and in hypothesizing the mechanisms
      that are put in play by MCS.

PMID- 18083501
TI  - Neurosurgical decision-making with IOM: DBS surgery.
AB  - Intraoperative monitoring (IOM) adds new information to intraoperative surgical
      decision-making. When presented clearly and accurately, it can help guide
      decision processes during the procedure, but can be a detriment overall if the
      information is inaccurate or misleading. Troubleshooting abilities and vigilance
      of the IOM staff play a large role in bolstering the level of trust a surgeon
      develops in IOM. Additionally, a surgeon may impart his own interpretation and
      experience with this new information that can undermine or enhance its impact on
      the case. In this article, we explore these issues with IOM in general and as
      they relate to the special context of DBS for movement disorders.

PMID- 18083502
TI  - Subthalamic nucleus stimulation in Parkinson's disease: postoperative CT-MRI
      fusion images confirm accuracy of electrode placement using intraoperative multi
      unit recording.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is increasingly
      used to treat advanced Parkinson's disease (PD). The optimal method for targeting
      the STN before implanting the definitive DBS electrode is still a matter of
      debates. Beside methods of direct visualization of the nucleus based on
      stereotactic magnetic resonance imaging (MRI), the most often used technique for
      targeting STN consists in recording single-cell activity along exploratory tracks
      of 10-15mm in length, centered on the theoretical or MRI-defined target
      coordinates. Single-unit recordings with a microelectrode present various
      drawbacks. They are time-consuming if correctly performed and a single-cell
      precision is probably superfluous, taking into account the size of the implanted
      electrode. In this study, we present an original method of recording and
      quantification of a multi-unit signal recorded intraoperatively with a semi
      microelectrode for targeting the STN. Twelve patients with advanced PD have been
      included and assessed clinically before and one year after bilateral STN-DBS
      electrode implantation guided by multi-unit electrophysiological recordings.
      After one year of chronic stimulation, all patients showed a marked clinical
      improvement. The motor score of the unified Parkinson's disease rating scale
      decreased by more than 57% and the required levodopa-equivalent daily dose by
      59.5% in on-stimulation off-medication condition compared to off-stimulation off
      medication condition. The accuracy of STN-DBS lead placement was confirmed on
      postoperative computed tomography (CT) scans, which were fused to preoperative T2
      weighted MRI. The boundaries of the STN were easily determined by an increase in
      multi-unit signal amplitude, which was observed on average from 0.492mm below the
      rostral border of the STN down to 0.325mm above its caudal border. Signal
      amplitude significantly increased at the both rostral and caudal STN margins
      (P<0.05) and the level of neuronal activity easily distinguished inside from
      outside the nucleus. This study showed that STN boundaries could be adequately
      determined on the basis of intraoperative multi-unit recording with a semi
      microelectrode. The accuracy of our method used for positioning DBS electrodes
      into the STN was confirmed both on CT-MRI fusion images and on the rate of
      therapeutic efficacy.

PMID- 18083503
TI  - Intraoperative neurophysiological assessment of disabling symptoms in DBS
      surgery.
AB  - INTRODUCTION: Neurophysiological assessment can provide quantitative measures for
      the selected motor signs that have been targeted for surgery and may be helpful
      in predicting the therapeutic effects of deep brain stimulation (DBS) on
      pathological tremor, motor performance, and rigidity. OBJECTIVE: To present a
      survey and demonstrate the contribution of neurophysiological assessment of side
      effects and effects on disabling motor symptoms at various steps of DBS surgery,
      and to confirm its role for optimal target localization, as an adjuvant to
      anatomic imaging. MATERIAL AND METHODS: The data result from 192 nuclei in 118
      procedures on patients with Parkinson's disease (84), essential tremor (24),
      Hallenvorder Spatz dystonia (4), multiple sclerosis (4), and Holmes tremor (2).
      The intraoperative neurophysiological monitoring (IOM) protocol consists of
      semimicroelectrode recording (for subthalamic nuclei), whereas
      accelerotransducers and spectral analysis allow assessment of tremor, finger
      tapping (FT), diadochokinesis (DDK), and determination of the distance between
      DBS electrodes and internal capsule (IC). Rigidity is assessed by surface EMG
      recordings in combination with a goniometer. RESULTS: The determination of the
      functional distance between the DBS electrode and the IC is based on the
      activation functions of axons in the IC. We show the high sensitivity of
      accelerometers for tremor over a large part of the body, the relationship between
      clinical scores and spectral frequencies of FT and DDK. Parkinsonian rigidity can
      be assessed from surface EMG (sEMG) by means of a balance coefficient, which can
      detect negative rigidity, for low unified Parkinson's disease rating scale
      (UPDRS) scores (0-2) and quantified EMG when negative rigidity is excluded.
      CONCLUSION: Accelerometer and sEMG recording have shown their value for
      intraoperative assessment of disabling motor symptoms and side effects during
      surgery, to optimize the target position electrodes for DBS. The combination with
      contemporary signal analyzing techniques permit intraoperative monitoring without
      a significant delay. IONM improves sensitivity and adds objective
      neurophysiological data.

PMID- 18083504
TI  - Conversion of plasma membrane topology during epithelial tube connection requires
      Arf-like 3 small GTPase in Drosophila.
AB  - The development of tubular organs often involves the hollowing of cells into a
      torus (doughnut shape), as observed in blood vessel formation in vertebrates and
      tracheal development in insects. During the fusion of Drosophila tracheal
      branches, fusion cells located at the tip of migrating branches contact each
      other and form intracellular luminal cavities on opposite sides of the cells that
      open to connect the tubule lumens. This process involves the intracellular fusion
      of plasma membranes associated with microtubule tracks. Here, we studied the
      function of an evolutionarily conserved small GTPase, Arf-like 3, in branch
      fusion. Arf-like 3 is N-terminally acetylated, and associates with both
      intracellular vesicles and microtubules. In Arf-like 3 mutants, the cell adhesion
      of fusion cells, specification of apical membrane domains, and secretion of
      luminal extracellular matrix proceeded normally, but the luminal cavities did not
      open due to the failure of intracellular fusion of the plasma membranes. We
      present evidence that the Arf-like 3 mutation impairs the localized assembly of
      the exocyst complex, suggesting that the targeting of exocytosis machinery to
      specific apical domains is the key step in converting the plasma membrane
      topology in fusion cells.

PMID- 18083505
TI  - Lycopus europaeus (Gypsywort): effects on the thyroidal parameters and symptoms
      associated with thyroid function.
AB  - The aim of the prospective two-armed open study was to examine the effect of
      Lycopi europaei herba on thyroid function and on associated symptoms during a 3
      month follow-up phase. The study population consisted of patients with a basal
      TSH<1.0 mU/l and hyperthyroidism-associated symptoms. For the first time, the
      T3/T4 excretion in 24h urine was measured as a primary objective parameter. As
      secondary parameters, further hormones, the general condition and the symptoms
      associated with hyperthyroidism were registered. The urinary T4 excretion was
      significantly increased in Lycopus europaeus-treated patients (p=0.032). It is
      supposed that renal mechanisms cause the increased T4 excretion either by a
      modification within the glomeruli or by impaired reabsorption. Symptoms being
      specific to the thyroid gland were diminished, as e.g. the increased heart rate
      in the morning. The Lycopus europaeus preparation showed a good tolerance. These
      findings confirm positive effects of Lycopus europaeus in slight forms of
      hyperthyroidism.

PMID- 18083506
TI  - Omega-3 polyunsaturated fatty acid supplementation reduces hypertension in
      TGR(mRen-2)27 rats.
AB  - To establish the effect of dietary omega-3 PUFA on angiotensin II (ANG II)
      mediated hypertension, male TGR (mRen-2)27 (Ren-2) rats (animals with high ANG II
      activity) were maintained on a diet either deficient or sufficient in omega-3
      PUFA from conception. Half the animals on each diet were treated with the
      angiotensin-converting enzyme inhibitor, perindopril, from birth. Ren-2 rats fed
      the omega-3 PUFA deficient diet were significantly more hypertensive than those
      fed the omega-3 PUFA sufficient diet. Perindopril reduced the blood pressure of
      both omega-3 PUFA-deficient and omega-3 PUFA-sufficient diet-fed Ren-2 rats. Body
      weight, body fat and plasma leptin were reduced by perindopril treatment but not
      affected by omega-3 PUFA supply. Given that the elevated blood pressure of the
      Ren-2 rat is mediated by ANG II, the data suggest that omega-3 PUFA may reduce
      hypertension via the renin-angiotensin system.

PMID- 18083507
TI  - Novel primary immunodeficiencies revealed by the investigation of paediatric
      infectious diseases.
AB  - Human primary immunodeficiencies impairing myeloid and/or lymphoid cellular
      responses to activating receptors other than antigen receptors have recently been
      described in children with various infectious diseases. Germline mutations in
      NEMO and IKBA impair NF-kappaB-mediated signalling, at least in response to the
      stimulation of TLRs, IL-1Rs and TNFRs, and confer a broad predisposition to
      infections. Mutations in IRAK4 selectively impair TLRs other than TLR3 and most
      IL-1R responses, and confer a predisposition to pyogenic bacterial diseases,
      including invasive pneumococcal disease in particular. Mutations in TLR3 and
      UNC93B1 impair TLR3 responses and confer a predisposition to herpes simplex
      encephalitis. Mutations in STAT1 impair IFN-gamma and/or IFN-alpha/beta responses
      and predispose subjects to mycobacterial and viral diseases, respectively.
      Mutations in IFNGR1 and IFNGR2 impair IFN-gamma responses and confer a
      predisposition to mycobacterial diseases. Mutations in IL12B and IL12RB1 impair
      IL-12 and IL-23 responses and predispose subjects to infections caused by
      mycobacteria and Salmonella. Finally, mutations in TYK2 and STAT3 mostly impair
      IL-6R responses, conferring a predisposition to staphylococcal disease in
      particular. The infectious phenotypes associated with these novel leukocyte
      activation deficiencies are therefore collectively diverse, tightly dependent on
      the morbid gene and affected pathway, and individually narrow, often restricted
      to one or a few infectious diseases.

PMID- 18083508
TI  - Intricate connections between innate and adaptive autoimmunity.

PMID- 18083509
TI  - Pathogenic autoantibodies in systemic sclerosis.
AB  - Systemic sclerosis, scleroderma, is a disease characterized by widespread
      vascular injury and fibrosis of the skin and visceral organs. Circulating
      autoantibodies against several intracellular antigens are common in scleroderma
      patients. The specificities of such autoantibodies correlate with distinct
      clinical manifestations. However, till date there is no evidence that these
      autoantibodies, though helpful in diagnosis and prognosis, are linked to the
      pathogenesis of scleroderma nor that they may cause any feature of the disease.
      Recently, the discovery of novel agonistic autoantibodies targeting the PDGF
      receptor has provided important insight into the molecular pathogenesis of
      scleroderma and the intracellular mechanisms leading to fibrosis. Although their
      pathogenic role awaits validation in in vivo models, these antibodies represent
      the molecular link between the immune system and fibrosis.

PMID- 18083510
TI  - Characterization of HSD17B1 sequence variants in breast cancer cases from French
      Canadian families with high risk of breast and ovarian cancer.
AB  - A family history of disease and estrogen exposure are risk factors for breast
      cancer. The HSD17B1 gene encodes a key steroidogenic enzyme that catalyses the
      final step of estradiol biosynthesis, rendering it a good candidate gene for
      breast cancer susceptibility. The current study was designed to screen for
      HSD17B1 germline mutations potentially involved in breast cancer susceptibility.
      DNA samples from 50 individuals affected with breast cancer from non-BRCA1/2
      French Canadian families with a high risk of breast and ovarian cancer were
      screened for sequence variants in HSD17B1. Our study identified 28 sequence
      variants, including three non-synonymous variants, p.Ala238Val, p.Arg259His,
      p.Ser313Gly, one of which (p.Arg259His) was not previously reported. Functional
      assays failed to show changes in either activity or recombinant proteins levels
      for all three variants. Thus, our resequencing analysis does not support the
      existence of deleterious, gain-of-function or transcription mutations in HSD17B1,
      which could explain the clustering of breast cancer cases in non-BRCA1/2 high
      risk French Canadian families. However, a haplotype-based approach was used to
      establish tSNPs, providing a valuable tool for further searches of common disease
      associated variants in this gene, using large cohorts.

PMID- 18083511
TI  - Immobilization of selected heavy metals in sewage sludge by natural zeolites.
AB  - This contribution presents the possibility of application of natural sorbent
      (Transcarpathian clinoptylolite (KL)) for immobilization of selected heavy metals
      in the sewage sludge. The influence of ion-exchange parameters (e.g. time, amount
      of zeolite) were discussed. Process of immobilization was performed using a
      static method (Batch). It was found that best possible conditions for
      immobilization of heavy metal ions were as follows: zeolite fraction 0.7-1.0mm,
      5h of shaking, zeolite/sewage sludge ratio 2/98.

PMID- 18083512
TI  - Triazole derivatives as non-nucleoside inhibitors of HIV-1 reverse transcriptase-
      structure-activity relationships and crystallographic analysis.
AB  - A series of 3,4,5-trisubstituted 1,2,4-4H triazole derivatives was synthesized
      and investigated for HIV-1 reverse transcriptase inhibition. An X-ray structure
      with HIV-1 RT secured the binding mode and allowed the key interactions with the
      enzyme to be identified.

PMID- 18083513
TI  - Synthesis and antispasmodic activity of lidocaine derivatives endowed with
      reduced local anesthetic action.
AB  - The present structure-activity relationship (SAR) study focused on chemical
      modifications of the structure of the local anesthetic lidocaine, and indicated
      analogues having reduced anesthetic potency, but with superior potency relative
      to the prototype in preventing anaphylactic or histamine-evoked ileum
      contraction. From the SAR analysis, 2-(diethylamino)-N-(trifluoromethyl-phenyl)
      and 2-(diethylamino)-N-(dimethyl-phenyl) acetamides were selected as the most
      promising compounds. New insights into the applicability of non-anesthetic
      lidocaine derivatives as templates in drug discovery for allergic syndromes are
      provided.

PMID- 18083514
TI  - Borderline breast lesions diagnosed at core needle biopsy: can magnetic resonance
      mammography rule out associated malignancy? Preliminary results based on 79
      surgically excised lesions.
AB  - The purpose of this study is to assess whether magnetic resonance mammography
      (MRM) can exclude associated malignancy in case of diagnosis of borderline breast
      lesions (B3) at core needle biopsy (CNB). Retrospective analysis of MRM findings
      of 79 borderline breast lesions (26 benign papillomas, 29 radial sclerosing
      lesions, 6 atypical ductal hyperplasias, 18 lobular neoplasias) diagnosed at CNB
      was performed. Lesions were classified as "non-suspicious" or "suspicious"
      according to Fischer score. These findings were compared to the results of
      histological analysis of the excisional specimens. Sensitivity, specificity,
      positive (PPV) and negative (NPV) predictive values of MRM in predicting the
      presence of malignancy were calculated. Out of 24 (30.4%) lesions classified as
      "suspicious", 8 (33.3%) proved to be malignant and 16 (66.7%) benign. Among the
      55 (69.6%) "non-suspicious" lesions, only 1 (1.8%) was malignant (low-grade
      ductal carcinoma in situ), while the remaining 54 (98.2%) proved to be benign.
      MRM sensitivity, specificity, PPV, and NPV were 88.9%, 77.1%, 33.3%, and 98.2%,
      respectively. When a borderline lesion is diagnosed on CNB, in case of mild or no
      enhancement at MRM, follow-up rather than excisional biopsy might be prompted.

PMID- 18083515
TI  - Aging and fertility patterns in wild chimpanzees provide insights into the
      evolution of menopause.
AB  - Human menopause is remarkable in that reproductive senescence is markedly
      accelerated relative to somatic aging, leaving an extended postreproductive
      period for a large proportion of women. Functional explanations for this are
      debated, in part because comparative data from closely related species are
      inadequate. Existing studies of chimpanzees are based on very small samples and
      have not provided clear conclusions about the reproductive function of aging
      females. These studies have not examined whether reproductive senescence in
      chimpanzees exceeds the pace of general aging, as in humans, or occurs in
      parallel with declines in overall health, as in many other animals. In order to
      remedy these problems, we examined fertility and mortality patterns in six free
      living chimpanzee populations. Chimpanzee and human birth rates show similar
      patterns of decline beginning in the fourth decade, suggesting that the
      physiology of reproductive senescence was relatively conserved in human
      evolution. However, in contrast to humans, chimpanzee fertility declines are
      consistent with declines in survivorship, and healthy females maintain high birth
      rates late into life. Thus, in contrast to recent claims, we find no evidence
      that menopause is a typical characteristic of chimpanzee life histories.

PMID- 18083516
TI  - Evidence for a genetic basis of aging in two wild vertebrate populations.
AB  - Aging, or senescence, defined as a decline in physiological function with age,
      has long been a focus of research interest for evolutionary biologists. How has
      natural selection failed to remove genetic effects responsible for such reduced
      fitness among older individuals? Current evolutionary theory explains this
      phenomenon by showing that, as a result of the risk of death from environmental
      causes that individuals experience, the force of selection inevitably weakens
      with age. This in turn means that genetic mutations having detrimental effects
      that are only felt late in life might persist in a population. Although widely
      accepted, this theory rests on the assumption that there is genetic variation for
      aging in natural systems, or (equivalently), that genotype-by-age interactions
      (GxA) occur for fitness. To date, empirical support for this assumption has come
      almost entirely from laboratory studies on invertebrate systems, most notably
      Drosophila and C. elegans, whereas tests of genetic variation for aging are
      largely lacking from natural populations. By using data from two wild mammal
      populations, we perform quantitative genetic analyses of fitness and provide the
      first evidence for a genetic basis of senescence to come from a study in the
      natural environment. We find evidence that genetic differences among individuals
      cause variation in their rates of aging and that additive genetic variance for
      fitness increases with age, as predicted by the evolutionary theory of
      senescence.

PMID- 18083517
TI  - Somatic and motor components of action simulation.
AB  - Seminal studies in monkeys report that the viewing of actions performed by other
      individuals activates frontal and parietal cortical areas typically involved in
      action planning and execution. That mirroring actions might rely on both motor
      and somatosensory components is suggested by reports that action observation and
      execution increase neural activity in motor and in somatosensory areas. This
      occurs not only during observation of naturalistic movements but also during the
      viewing of biomechanically impossible movements that tap the afferent component
      of action, possibly by eliciting strong somatic feelings in the onlooker.
      Although somatosensory feedback is inherently linked to action execution,
      information on the possible causative role of frontal and parietal cortices in
      simulating motor and sensory action components is lacking. By combining low
      frequency repetitive and single-pulse transcranial magnetic stimulation, we found
      that virtual lesions of ventral premotor cortex (vPMc) and primary somatosensory
      cortex (S1) suppressed mirror motor facilitation contingent upon observation of
      possible and impossible movements, respectively. In contrast, virtual lesions of
      primary motor cortex did not influence mirror motor facilitation. The reported
      double dissociation suggests that vPMc and S1 play an active, differential role
      in simulating efferent and afferent components of observed actions.

PMID- 18083518
TI  - Investigating action understanding: inferential processes versus action
      simulation.
AB  - In our daily life, we continuously monitor others' behaviors and interpret them
      in terms of goals, intentions, and reasons. Despite their central importance for
      predicting and interpreting each other's actions, the functional mechanisms and
      neural circuits involved in action understanding remain highly controversial. Two
      alternative accounts have been advanced. Simulation theory assumes that we
      understand actions by simulating the observed behavior through a direct matching
      process that activates the mirror-neuron circuit. The alternative interpretive
      account assumes that action understanding is based on specialized inferential
      processes activating brain areas with no mirror properties. Although both
      approaches recognize the central role of contextual information in specifying
      action intentions, their respective accounts of this process differ in
      significant respects. Here, we investigated the role of context in action
      understanding by using functional brain imaging while participants observed an
      unusual action in implausible versus plausible contexts. We show that brain areas
      that are part of a network involved in inferential interpretive processes of
      rationalization and mentalization but that lack mirror properties are more active
      when the action occurs in an implausible context. However, no differential
      activation was found in the mirror network. Our findings support the assumption
      that action understanding in novel situations is primarily mediated by an
      inferential interpretive system rather than the mirror system.

PMID- 18083519
TI  - Intermediate filament assembly: dynamics to disease.
AB  - Intermediate filament (IF) proteins belong to a large and diverse gene family
      with broad representation in vertebrate tissues. Although considered the
      'toughest' cytoskeletal fibers, studies in cultured cells have revealed that IF
      can be surprisingly dynamic and highly regulated. This review examines the
      diversity of IF assembly behaviors, and considers the ideas that IF proteins are
      co- or post-translationally assembled into oligomeric precursors, which can be
      delivered to different subcellular compartments by microtubules or actomyosin and
      associated motor proteins. Their interaction with other cellular elements via IF
      associated proteins (IFAPs) affects IF dynamics and also results in cellular
      networks with properties that transcend those of individual components. We end by
      discussing how mutations leading to defects in IF assembly, network formation or
      IF-IFAP association compromise in vivo functions of IF as protectors against
      environmental stress.

PMID- 18083520
TI  - Docking and hydropathic scoring of polysubstituted pyrrole compounds with
      antitubulin activity.
AB  - Compounds that bind at the colchicine site of tubulin have drawn considerable
      attention with studies indicating that these agents suppress microtubule dynamics
      and inhibit tubulin polymerization. Data for 18 polysubstituted pyrrole compounds
      are reported, including antiproliferative activity against human MDA-MB-435 cells
      and calculated free energies of binding following docking the compounds into
      models of alphabeta-tubulin. These docking calculations coupled with HINT
      interaction analyses are able to represent the complex structures and the binding
      modes of inhibitors such that calculated and measured free energies of binding
      correlate with an r(2) of 0.76. Structural analysis of the binding pocket
      identifies important intermolecular contacts that mediate binding. As seen
      experimentally, the complex with JG-03-14 (3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H
      pyrrole-2-carboxylic acid ethyl ester) is the most stable. These results
      illuminate the binding process and should be valuable in the design of new
      pyrrole-based colchicine site inhibitors as these compounds have very accessible
      syntheses.

PMID- 18083521
TI  - Omega-(2-Naphthyloxy) amino alkanes as a novel class of anti-hyperglycemic and
      lipid lowering agents.
AB  - omega-(2-Naphthyloxy) amino alkanes, obtained as major by-product during course
      of synthesis of carbamate esters from omega-(2-naphthyloxy) alkyl halides and
      amines, showed significant anti-hyperglycemic and lipid lowering activities in
      various test models as a novel class of compounds. Compounds were tested in rat
      GLM, SLM, STZ, and STZ-S models at 100mg/kg dose. Of these compound 13 was found
      to be the most active which caused lowering of sugar by 33.6%, 31.0%, 28.5%, and
      73.8% in GLM, SLM, STZ, STZ-S, and db/db mice models, respectively. It also
      significantly effected lowering of LDL in rat model and also in Hamster model
      without reducing HDL. Most of the compounds showing anti-diabetic and lipid
      lowering activity have shown promising PPAR-alpha/gamma/delta-activity. Compounds
      6, 13, and 19 have shown very good PPAR-alpha/gamma/delta activity.

PMID- 18083522
TI  - N(delta)-Methylated L-arginine derivatives and their effects on the nitric oxide
      generating system.
AB  - So far N(delta)-methyl-l-arginine (MA) is only detected in yeast cells. Assuming
      that MA also exists in mammalians we examined possible physiological effects of
      N(delta)-methylated l-arginine derivatives on the nitric oxide generating system,
      that is, nitric oxide synthase (NOS), arginase and dimethylarginine
      dimethylaminohydrolase (DDAH). N(delta)-methyl-l-citrulline (MC) turned out to be
      a weak non-specific inhibitor of nitric oxide synthases. Moreover, MA is
      hydroxylated by all human NOS isoforms to N(omega)-hydroxy-N(delta)-methyl-l
      arginine (NHAM) but not converted further. This hydroxylated intermediate,
      however, was detected to be a potent inhibitor of bovine liver arginase with a
      K(i) of 17.1+/-2.2 microM.

PMID- 18083523
TI  - Requirement of beta-alanine components in sequence-specific DNA alkylation by
      pyrrole-imidazole conjugates with seven-base pair recognition.
AB  - To investigate the effect of incorporation of beta-alanine in alkylating N
      methylpyrrole (Py)-N-methylimidazole (Im) polyamide, seco-CBI conjugates 2-8 were
      synthesized by an Fmoc solid-phase method and subsequent coupling with an
      alkylating moiety. DNA-alkylating activities of conjugates 2-8 were evaluated by
      high-resolution denaturing gel electrophoresis with 202-base pair (bp) DNA
      fragments. Alkylation by conjugates 2 and 3, which have antiparallel pairings of
      beta-alanine (beta) opposite beta (beta/beta) and Py/beta, occurred mainly at the
      adenine (A) of the matching sequences, 5'-AGCTCCA-3' (site 1) and 5'-AGCACCA-3'
      (site 3). However, conjugate 4, with beta/Py, did not show any DNA-alkylating
      activities. Similarly, conjugate 5, which possessed a Py/Py pair, weakly
      alkylated the matching sites at micromolar concentrations. Conjugates 6 and 7,
      which possessed beta/beta and Py/beta pairs, respectively, alkylated at the A of
      the matching sequences, 5'-ACTACCA-3' (site 2) and 5'-ACAACCA-3' (site 4). In
      contrast, conjugated 8, with a Py/Py pair, showed lower activity and less
      alkylated DNA at sites 2 and 4 with mismatched alkylation at site 1 at a higher
      concentration than that of 6 and 7. These results demonstrate that incorporation
      of beta-alanine is required for the sequence-specific alkylation by seco-CBI Py
      Im conjugates with a seven-base pair sequence.

PMID- 18083524
TI  - Activation and inhibition of DNA methyltransferases by S-adenosyl-L-homocysteine
      analogues.
AB  - The inhibition of methyltransferases is currently of high interest, particularly
      in the areas of microbial infection and cell proliferation, as there have been
      serious attempts to develop novel anti-microbial agents. In the present
      investigation, a series of 11 S-adenosyl-l-homocysteine analogues have been
      synthesized and effect of these analogues on DNA methylation catalyzed by DNA
      methyltransferases was studied. It was found that, while 5'-S-(propionic acid)5'
      deoxy-9-(1'-beta-d-ribofuranosyl)1,3-dideazaadenine was an activator of EcoP15I
      and HhaI DNA methyltransferases, 5'-S-(propionic acid)5'-deoxy-9-(1'-beta
      dribofuranosyl)adenine inhibited the methyltransferases in a non-competitive
      manner. An understanding of the binding of analogues to DNA methyltransferases
      will greatly assist the design of novel anti-microbial compounds.

PMID- 18083525
TI  - Gas-phase ion/ion reactions of transition metal complex cations with multiply
      charged oligodeoxynucleotide anions.
AB  - Multiply deprotonated hexadeoxyadenylate anions, (A6-nH)(n-), where n = 3-5, have
      been subjected to reaction with a range of divalent transition-metal complex
      cations in the gas phase. The cations studied included the bis- and tris-1,10
      phenanthroline complexes of CuII, FeII, and CoII, as well as the tris-1,10
      phenanthroline complex of RuII. In addition, the hexadeoxyadenylate anions were
      subjected to reaction with the singly charged FeIII and CoIIIN,N'
      ethylenebis(salicylideneiminato) complexes. The major competing reaction channels
      are electron-transfer from the oligodeoxynucleotide anion to the cation, the
      formation of a complex between the anion and cation, and the incorporation of the
      transition-metal into the oligodeoxynucleotide. The latter process proceeds via
      the anion/cation complex and involves displacement of the ligand(s) in the
      transition-metal complex by the oligodeoxynucleotide. Competition between the
      various reaction channels is governed by the identity of the transition-metal
      cation, the coordination environment of the metal complex, and the
      oligodeoxynucleotide charge state. In the case of the divalent metal
      phenanthroline complexes, competition between electron-transfer and metal ion
      incorporation is particularly sensitive to the coordination number of the reagent
      metal complexes. Both electron-transfer and metal ion incorporation occur to
      significant extents with the bis-phenanthroline ions, whereas the tris
      phenanthroline ions react predominantly by metal ion incorporation. To our
      knowledge this work reports the first observations of the gas-phase incorporation
      of multivalent transition-metal cations into oligodeoxynucleotide anions and
      represents a means for the selective incorporation of transition-metal counter
      ions into gaseous oligodeoxynucleotides.

PMID- 18083526
TI  - Impact of proline and aspartic acid residues on the dissociation of
      intermolecularly crosslinked peptides.
AB  - The dissociation of intermolecularly crosslinked peptides was evaluated for a
      series of peptides with proline or aspartic acid residues positioned adjacent to
      the crosslinking sites (lysine residues). The peptides were crosslinked with
      either disuccinimidyl suberate (DSS) or disuccinimidyl L-tartrate (DST), and the
      influence of proline and aspartic acid residues on the fragmentation patterns
      were investigated for precursor ions with and without a mobile proton.
      Collisionally activated dissociation (CAD) spectra of aspartic acid-containing
      crosslinked peptide ions, doubly-charged with both protons sequestered, were
      dominated by cleavage C-terminal to the Asp residue, similar to that of
      unmodified peptides. The proline-containing crosslinked peptides exhibited a high
      degree of internal ion formation, with the resulting product ions having an N
      terminal proline residue. Upon dissociation of the doubly-charged crosslinked
      peptides, twenty to fifty percent of the fragment ion abundance was accounted for
      by multiple cleavage products. Crosslinked peptides possessing a mobile proton
      yielded almost a full series of b- and y-type fragment ions, with only proline
      directed fragments still observed at high abundances. Interestingly, the
      crosslinked peptides exhibited a tendency to dissociate at the amide bond C
      terminal to the crosslinked lysine residue, relative to the N-terminal side. One
      could envision updating computer algorithms to include these crosslinker specific
      product ions--particularly for precursor ions with localized protons--that
      provide complementary and confirmatory information, to offer more confident
      identification of both the crosslinked peptides and the location of the
      crosslink, as well as affording predictive guidelines for interpretation of the
      product-ion spectra of crosslinked peptides.

PMID- 18083527
TI  - Evolution of instrumentation for the study of gas-phase ion/ion chemistry via
      mass spectrometry.
AB  - The scope of gas-phase ion/ion chemistry accessible to mass spectrometry is
      largely defined by the available tools. Due to the development of novel
      instrumentation, a wide range of reaction phenomenologies has been noted, many of
      which have been studied extensively and exploited for analytical applications.
      This perspective presents the development of mass spectrometry-based
      instrumentation for the study of the gas-phase ion/ion chemistry in which at
      least one of the reactants is multiply charged. The instrument evolution is
      presented within the context of three essential elements required for any ion/ion
      reaction study: the ionization source(s), the reaction vessel or environment, and
      the mass analyzer. Ionization source arrangements have included source
      combinations that allow for reactions between multiply charged ions of one
      polarity and singly charged ions of opposite polarity, arrangements that enable
      the study of reactions of multiply charged ions of opposite polarity and, most
      recently, arrangements that allow for ion formation from more than two ion
      sources. Gas-phase ion/ion reaction studies have been performed at near
      atmospheric pressure in flow reactor designs and within electrodynamic ion traps
      operated in the mTorr range. With ion trap as a reaction vessel, ionization and
      reaction processes can be independently optimized and ion/ion reactions can be
      implemented within the context of MSn experiments. Spatial separation of the
      reaction vessel from the mass analyzer allows for the use of any form of mass
      analysis in conjunction with ion/ion reactions. Time-of-flight mass analysis, for
      example, has provided significant improvements in mass analysis figures of merit
      relative to mass filters and ion traps.

PMID- 18083528
TI  - Regioselectivity of human UDP-glucuronosyl-transferase 1A1 in the synthesis of
      flavonoid glucuronides determined by metal complexation and tandem mass
      spectrometry.
AB  - A three-part tandem mass spectrometric strategy that entails MSn analysis and a
      post-column LC-MS cobalt complexation method is developed to identify flavonoid
      monoglucuronide metabolites synthesized using the 1A1 isozyme of human UDP
      glucuronosyltransferase (UGT). Ten flavonoid aglycons were used as substrates,
      spanning the subclasses of flavones, flavonols, and flavanones. The products were
      characterized by LC-MS and LC-MSn, with post-column cobalt complexation employed
      to pinpoint the specific sites of conjugation. The dissociation of complexes of
      the form [Co(II) (flavonoid glucuronide - H) (4,7-diphenyl-1,10
      phenanthroline)(2)]+ allowed identification of the products and differentiation
      of isomers. The correlation between glycosylation site and elution order is used
      to provide additional structural confirmation. Flavonoids lacking a 3' hydroxyl
      group were glucuronidated only at position 7, while those containing this
      functionality also formed 3'-O-glucuronides and sometimes 4'-O-glucuronides, thus
      supporting the conclusion that the presence or absence of the 3'-OH group is the
      major determinant of the regioselectivity of glucuronidation. Moreover, the
      specific distribution of multiple glucuronide products (7-O, 3'-O, 4'-O) is
      governed by the subclass of flavonoid.

PMID- 18083529
TI  - The analysis of polystyrene and polystyrene aggregates into the mega dalton mass
      range by cryodetection MALDI TOF MS.
AB  - Mass spectra of atactic polystyrene were collected into the mega-dalton mass
      range with a matrix-assisted laser desorption ionization time of flight (MALDI
      TOF) mass spectrometer, which incorporates a cryodetector comprised of an array
      of 16 superconducting tunnel junctions (STJ). The STJ cryodetector,
      theoretically, has no loss in signal response at any mass compared with the
      reduced signal found at high mass when using a conventional secondary-ionization
      detector. Since ion detection at high m/z is one of the fundamental limitations
      of mass spectrometry (MS), the cryodetector was used to explore the high m/z
      limit of the MALDI TOF technique for the analysis of two polymer types. Mass
      spectra were collected for polystyrene at Mn 170, 400, 900, and 2000 kDa and
      polymethyl methacrylate (PMMA) at Mn 62.6 kDa and 153.7 kDa. For polystyrene, the
      data showed a trend toward increased aggregation and charge state with mass. The
      Mn 2 MDa polystyrene data revealed a peak at m/z 2.2 MegaTh and a charge state
      analysis revealed that these ions were primarily polystyrene aggregates with a
      mass of approximately 4 MDa. This aggregate assignment was possible because the
      cryodetector response allows for the determination of a charge state up to about
      four. The contribution of each charge state for a selected peak can be determined
      in this fashion. This analysis revealed the preferential formation of doubly
      charged even-numbered aggregates over odd-numbered aggregates for high molecular
      mass polystyrene. A potential mechanism for the aggregation process for doubly
      charged species is discussed.

PMID- 18083530
TI  - Targeting the development and effector functions of TH17 cells.
AB  - T helper (TH) cells can assume different phenotypes characterized by the
      secretion of distinct effector molecules. Interferon-gamma producing TH1 and IL-4
      producing TH2 cells have long been recognized as important mediators of host
      defense, whereas regulatory T cells are known to suppress T cell responses.
      Recently, TH17 cells were characterized as a novel CD4(+) subset that
      preferentially produces IL-17, IL-17F, and IL-22 as the signature cytokines. TH17
      cells appear to play a critical role in sustaining the inflammatory response and
      their presence is closely associated with autoimmune disease, which makes them an
      attractive therapeutic target. In this review, we focus on the mechanisms that
      regulate the differentiation of naive T cells into TH17 cells and on TH17
      effector cytokines, as they represent opportunities for therapeutic intervention.

PMID- 18083531
TI  - Immune response to biologic scaffold materials.
AB  - Biologic scaffold materials composed of mammalian extracellular matrix are
      commonly used in regenerative medicine and in surgical procedures for the
      reconstruction of numerous tissue and organs. These biologic materials are
      typically allogeneic or xenogeneic in origin and are derived from tissues such as
      small intestine, urinary bladder, dermis, and pericardium. The innate and
      acquired host immune response to these biologic materials and the effect of the
      immune response upon downstream remodeling events has been largely unexplored.
      Variables that affect the host response include manufacturing processes, the rate
      of scaffold degradation, and the presence of cross species antigens. This
      manuscript provides an overview of studies that have evaluated the immune
      response to biologic scaffold materials and variables that affect this response.

PMID- 18083532
TI  - LPS-induced down-regulation of NO-sensitive guanylyl cyclase in astrocytes occurs
      by proteasomal degradation in clastosomes.
AB  - We previously showed that treatment with bacterial lipopolysaccharide (LPS) or
      pro-inflammatory cytokines decreases NO-sensitive guanylyl cyclase (GC(NO))
      activity in astrocytes by decreasing the half-life of the obligate GC(NO) beta1
      subunit in a NO-independent but transcription- and translation-dependent process.
      Here we show that LPS-induced beta1 degradation requires proteasome activity and
      is independent of NFkappaB activation or beta1 interaction with HSP90.
      Immunocytochemistry and confocal microscopy analysis revealed that LPS promotes
      colocalization of the predominantly soluble beta1 protein with ubiquitin and the
      20S proteasome in nuclear aggregates that present characteristics of clastosomes,
      nuclear bodies involved in proteolysis via the ubiquitin-proteasome system.
      Proteasome and protein synthesis inhibitors prevented LPS-induced clastosome
      assembly and nuclear colocalization of beta1 with ubiquitin and 20S proteasome,
      strongly supporting a role for these transient nuclear structures in GC(NO) down
      regulation during neuroinflammation.

PMID- 18083533
TI  - Cloning, expression and characterization of a thermotolerant endoglucanase from
      Syncephalastrum racemosum (BCC18080) in Pichia pastoris.
AB  - Endoglucanase is a major cellulolytic enzyme produced by Syncephalastrum
      racemosum (BCC18080). Preliminary results showed that this endoglucanase is
      thermotolerant as it retained more than 50% of its activity after incubation at
      80 degrees C for an hour. As this property may be of industrial use, we have
      cloned the full-length BCC18080 endoglucanase gene of 1020 nucleotides. Sequence
      analysis suggested that it belonged to the glycosyl hydrolase family 45. N
      terminal sequencing and analysis by SignalP program suggested that the first 32
      amino acid residues encoded the signal peptide. Expression of the recombinant
      clones with and without its own signal peptide in Pichia pastoris demonstrated
      that P. pastoris produced active 55 and 30 kDa secreted proteins. N-terminal
      sequencing suggested that the 55 kDa band was the mature protein while the 30 kDa
      band was the truncated protein. Glycoprotein analysis showed that the 55 kDa
      protein was glycosylated; while the smaller protein was not. All recombinant
      endoglucanases showed optimal temperature of 70 degrees C and optimal pH of 5-6.
      They retained more than 50% activity for 4h at 70 degrees C. In addition, high
      k(cat) and low apparent K(m) of these recombinant proteins indicated good
      properties of this enzyme against carboxylmethylcellulose.

PMID- 18083534
TI  - Interactive effect of paraoxonase-1 Q192R polymorphism and smoking history on the
      lung function decline in grain workers.
AB  - PURPOSE: This retrospective longitudinal study investigated the association
      between the Q192R polymorphism of the high-density lipoprotein-associated
      multifunctional antioxidant enzyme, paraoxonase-1 (PON1), and lung function
      decline, while taking into account smoking history. METHODS: The demographic,
      occupational, and respiratory symptom information and lung function variables
      were obtained from 216 male Saskatchewan grain workers. RESULTS: An interaction
      between the PON1 genotypes and smoking status was observed. Current smokers with
      the 192R allele had a lower forced expiratory volume in the first second (FEV(1))
      and FEV(1) per forced vital capacity (FVC). The annual decline rate of FEV(1)/FVC
      in current smokers was greater among 192R allele carriers than noncarriers
      (0.58+/-0.05 vs. 0.35+/-0.04 %/yr, p<0.0001). A similar result was observed with
      FEV(1) (40.9+/-6.4 vs. -33.0+/-7.0 mL/yr, p=0.10). The annual decline rate of FVC
      was not influenced by the genotypes. CONCLUSIONS: These results strengthened the
      previous findings of our cross-sectional study, suggesting that the 192R allele
      may be a novel genetic risk factor for airway injury among current smokers.

PMID- 18083535
TI  - Birth weight does not predict blood pressure in a young working population: a
      sharp (Scottish Heart and Arterial Disease Risk Prevention) study.
AB  - PURPOSE: We sought to assess the association between birth weight and adult
      systolic blood pressure in a relatively young, healthy, working population with
      prospectively collected birth data and blood pressure consistently recorded.
      METHODS: Detailed information on pregnancy and birth came from the Walker cohort,
      a database of babies born in Dundee, Scotland 1952-1966. Follow-up was conducted
      through record linkage to demographic and health information from the SHARP
      (Scottish Heart and Arterial Disease Risk Prevention) cohort, a working
      population screened for cardiovascular risk factors between 1991 and 1993.
      RESULTS: There were 1158 (56% male) subjects with a mean age of 32.1 years.
      Multivariable regression analysis showed no association between birth weight and
      systolic blood pressure when adjusted for age, gender, body mass index (BMI),
      cigarettes and alcohol, and social class B=0.04 (95% confidence interval -1.37,
      1.45). A decrease of 0.1 mm Hg for each 1-kg increase in birth weight was
      observed after additional adjustment for parental high blood pressure but was not
      statistically significant. BMI and male gender were predictors of increasing
      blood pressure. A parental history of high blood pressure showed an increase in
      systolic blood pressure of 4.1 mmHg (maternal) and 3.0 mm Hg (paternal).
      CONCLUSION: We were unable to demonstrate an inverse association between birth
      weight and systolic blood pressure. In this cohort, BMI and male sex remain
      consistent influences on blood pressure.

PMID- 18083536
TI  - Hemoglobin and overt nephropathy complications in type 1 diabetes.
AB  - PURPOSE: Anemia tends to be more severe and occur earlier in individuals with
      diabetic nephropathy. We thus examined whether hemoglobin (HGB) relates to end
      stage renal disease (ESRD), coronary artery disease (CAD), and all cause
      mortality in type 1 diabetes (T1D) subjects with overt nephropathy (ON). METHODS:
      We prospectively followed up 174 individuals with childhood-onset T1D and ON
      (albumin excretion rate >200 microg/min in multiple urine samples) from the
      Pittsburgh Epidemiology of Diabetes Complications Study cohort for 12 years. One
      hundred forty persons had ON at baseline, whereas another 34 were followed up
      from their incidence of ON as determined by biennial examinations. RESULTS:
      Baseline HGB inversely predicted ESRD (hazard ratio [HR] = 0.70, 0.61-0.80) and
      mortality (HR = 0.84, 0.72-0.98), but not CAD (HR = 0.91, 0.79-1.0). After
      adjustment for sex, diabetes duration, and other known risk factors, HGB remained
      significantly predictive of ESRD (HR = 0.72, 0.61-0.85), but not CAD (HR = 0.94,
      0.80-1.10) or overall mortality (HR = 0.92, 0.77-1.10). However, in those who
      never progressed to ESRD, HGB was significantly predictive of mortality (HR =
      0.59, 0.39-0.89). After including ESRD as a time-dependent, HGB was significantly
      predictive of overall mortality (HR = 0.75, 0.59-0.93). Gender-specific analyses,
      although limited by sample size, suggests similarity in the association between
      absolute HGB and ESRD in both genders, but differences for CAD and mortality.
      CONCLUSION: Our data suggest that in T1D with ON, a higher HGB level is
      associated not only with reduced risk of ESRD, but also of mortality,
      particularly in those who do not develop ESRD. HGB, even in the clinically normal
      range, is able to predict long-term complications in those with T1D and ON.

PMID- 18083537
TI  - Heavy smoking raises risk for type 2 diabetes mellitus in obese men; but, light
      smoking reduces the risk in lean men: a follow-up study in Japan.
AB  - PURPOSE: To investigate interactive effects of cigarette smoking and body mass
      index (BMI, measured in kilograms per square meter) on the risk for type 2
      diabetes mellitus (DM). METHODS: We conducted a follow-up study in 16,829
      apparently healthy men 30 to 59 years of age. At baseline, 23.1%, 24.6%, 24.0%,
      and 28.4% of the men were 'never' smokers, ex-smokers, light smokers (<or=20
      cigarettes/d), and heavy smokers (>20 cigarettes/d), respectively. BMI was
      expediently categorized into quartiles (Q1: <21.3; Q2: 21.3-22.9; Q3: 23.0-24.7;
      and Q4: >24.7 kg/m2). Incident DM was identified by a fasting serum glucose level
      of 7.00 mmol/L or higher or the criterion 'under treatment for DM.' The risk
      ratio for incident DM, hazard ratio (HR) and the 95% confidence interval (CI),
      according to smoking and BMI, were estimated by using Cox proportional hazard
      models. Age, drinking, exercise, and education were computed as confounders.
      RESULTS: During mean follow-up of 7.4 years, 869 men developed DM. In Q4 of BMI,
      heavy smoking raised the risk against 'never smoking' (multivariate-adjusted HR
      (95%CI): 1.37 [1.05-1.80]), but neither light smoking nor ex-smoking did. In Q1
      of BMI, light and heavy smoking reduced the risk (multivariate-adjusted HR (95%
      CI): 0.45 (0.23-0.88) and 0.74 (0.41-1.33), respectively). CONCLUSIONS: Smoking
      and BMI interactively influence risk for DM and the interaction is considerably
      complex. Heavy smoking moderately increases the risk for DM in obese men. But,
      light smoking reduces the risk in lean men.

PMID- 18083538
TI  - Prenatal caffeine assessment: fetal and maternal biomarkers or self-reported
      intake?
AB  - PURPOSE: We sought to examine associations among measures of caffeine exposure,
      including maternal urine, umbilical cord blood, and maternal self report.
      METHODS: Pregnant women were recruited from 56 obstetric practices and 15 clinics
      associated with six hospitals in Connecticut and Massachusetts between September
      1996 and January 2000; 3633 women were enrolled. Maternal urine throughout
      pregnancy and umbilical cord blood samples were analyzed for caffeine,
      paraxanthine, theophylline, and theobromine. Maternal caffeine intake was
      assessed throughout pregnancy. RESULTS: Urinary and cord blood biomarkers were
      correlated with reported intake throughout pregnancy (range r = 0.35-0.66; p <
      0.0001). Infants of smokers had greater cord blood concentrations of
      paraxanthine, reflecting faster caffeine metabolism in smokers, and cord blood
      paraxanthine levels were more strongly correlated with intake in smokers.
      CONCLUSION: Maternal self reported intake may still be the optimal and most valid
      measure of antenatal caffeine exposure, since biomarkers do not reflect exposure
      over pregnancy.

PMID- 18083539
TI  - Frequency of attendance at religious services and mortality in a U.S. national
      cohort.
AB  - OBJECTIVE: Few nationally representative cohort studies have appeared on
      frequency of attendance at religious services and mortality. We test the
      hypothesis that > weekly attendance compared with nonattendance at religious
      services is associated with lower probability of future mortality in such a
      study. METHODS: Data were analyzed from a longitudinal follow-up study of 8450
      American men and women age 40 years and older who were examined from 1988 to 1994
      and followed an average of 8.5 years. Measurements at baseline included self
      reported frequency of attendance at religious services, sociodemographics, and
      health, physical and biochemical measurements. RESULTS: Death during follow-up
      occurred in 2058. After adjusting for confounding by baseline sociodemographics
      and health status, the hazards ratios (95% confidence limits) were never 1.00
      (reference); < weekly 0.89 (0.75-1.04), p = 0.15; weekly 0.82 (0.71-0.94) p =
      0.005; and > weekly attenders 0.70 (0.59-0.83), p < 0.001. Mediators, including
      health behaviors and inflammation, explained part of the association.
      CONCLUSIONS: In a nationwide cohort of Americans, predominantly Christians,
      analyses demonstrated a lower risk of death independent of confounders among
      those reporting religious attendance at least weekly compared to never. The
      association was substantially mediated by health behaviors and other risk
      factors.

PMID- 18083540
TI  - Prevalence and characteristics of children with autism-spectrum disorders.
AB  - PURPOSE: The purpose of this study was to determine the prevalence of autism
      spectrum disorders (ASD) and associated characteristics among 8-year-old
      children. METHODS: This is an ongoing active, population-based surveillance
      program conducted in South Carolina as part of the Centers for Disease Control
      and Prevention's Autism and Developmental Disabilities Monitoring Network. Cases
      from the state's first two study years (2000 and 2002) have been combined for
      analysis, resulting in surveillance of 47,726 children who are 8 years of age.
      RESULTS: A total of 295 children met criteria for ASD, yielding a prevalence of
      6.2 per 1000. The racial distribution of cases was similar to that of 8-year-old
      children in the study area, with boys more commonly affected than girls (3.1:1).
      Seventy-nine percent of cases were served in special education, 36% of these
      under Autism classification. Analyses by gender showed differences in diagnostic
      criteria and intellectual functioning. Girls more often were cognitively impaired
      (IQ <or= 70) than boys (72.7% vs. 56.4%), although among those most severely
      impaired (IQ <or= 34), boys and girls were equally represented. CONCLUSIONS:
      Results indicate that ASDs affect 1 in 162 children 8 years of age in South
      Carolina. Continuing surveillance will permit assessment of potential changes in
      this prevalence estimate over time.

PMID- 18083541
TI  - Race in epidemiology: new tools, old problems.

PMID- 18083542
TI  - Capture-recapture estimates of nonfatal workplace injuries and illnesses.
AB  - PURPOSE: We examine reporting of nonfatal injury and illness reporting for the
      two most important sources of such data in the United States: workers'
      compensation data and the Bureau of Labor Statistics' (BLS) annual Survey of
      Occupational Injuries and Illnesses. METHODS: We linked individual case records
      from establishments reporting to the BLS with individual cases reported to
      workers' compensation systems in six states for 1998-2002 and used capture
      recapture analysis to estimate the proportion of injuries reported. Data are for
      private sector workers and exclude mining, railroad and water transportation,
      temporary employment agencies, membership organizations, and small agricultural
      establishments. RESULTS: For injuries and illnesses eligible for income benefits,
      using conservative assumptions, we estimate that workers' compensation systems in
      the six states missed over 180,000 lost-time injuries in the sampled industries,
      that the BLS survey missed almost 340,000, and that about 69,000 injuries were
      unreported to either system. CONCLUSIONS: Underreporting of nonfatal occupational
      injury and illness is substantial in both systems, but particularly in the Survey
      of Occupational Injuries and Illnesses. Using both sources improves coverage but
      falls far short of an accurate count for four of the six states. Reporting rates
      vary widely, so we cannot infer them for the entire United States.

PMID- 18083543
TI  - Determinants of physical inactivity among men and women from Greece: a 5-year
      follow-up of the ATTICA study.
AB  - OBJECTIVE: We sought to evaluate factors that are associated with physical
      activity changes among adults within a 5-year period. METHODS: From May 2001 to
      December 2002 we randomly enrolled 1514 men and 1528 women without any evidence
      of cardiovascular or any other chronic disease. The sampling was stratified by
      the age-gender distribution of the greater area of Athens. Weekly energy
      expenditure assessed by considering frequency, duration, and intensity of sports
      related physical activity. During 2006, the 5-year follow-up was performed in
      1955 participants, which included, among others, current physical activity
      status. RESULTS: A total of 587 (61%) men and 673 (68%) women were classified as
      physically inactive at baseline, whereas 661 (69%) men and 728 (73%) women were
      classified as physically inactive at follow-up; thus, a 13% increase in physical
      inactivity rate was observed in men and a 7% in women during the follow-up period
      (p < 0.01). Multivariate analysis revealed that male gender, being a nonsmoker,
      healthy eating, better self-reported quality-of-life, and lower prevalence of
      hypercholesterolemia and incidence of cardiovascular disease were the
      characteristics of people that remained physically active; advanced age, anxiety
      and depression, overweight, and low quality-of-life were the baseline predictors
      of physical inactivity among initially active participants, which also had a
      greater incidence of cardiovascular disease. CONCLUSIONS: Gender, aging,
      psychological disorders, body mass, smoking, dietary habits, perceived health
      status, and quality-of-life were the most important discriminating factors of
      physical activity changes.

PMID- 18083544
TI  - Trajectory and socioeconomic predictors of depression in a prospective study of
      residents of New York City.
AB  - PURPOSE: Past research has demonstrated the high prevalence of depression in the
      general population. However, few longitudinal studies have characterized the
      patterns of depression in a large, representative sample of the general
      population. We monitored symptoms of depression and assessed the factors
      associated with changing symptoms of depression in a population-based cohort over
      a 30 month period. METHODS: Using telephone surveys, we recruited 2752 adult
      residents of New York City in 2002. Persons were re-contacted after baseline for
      telephone interviews at 6 months, 18 months, and 30 months. RESULTS: Among study
      participants, symptoms of depression were common, often resolved within 6 months,
      but tended to recur. Participants with a past history of depressive symptoms were
      more at risk of later developing depression, even if they were asymptomatic at
      baseline. Factors significantly associated with subsequent symptoms included less
      social support at baseline, income below a threshold of $50,000, life stressors,
      poor health, and being separated. Lower levels of social support and lifetime
      stressors were only significantly associated with symptoms in participants with
      multiple episodes of depression. The influence of recent stressful events was
      also higher among participants with multiple episodes of depression. CONCLUSION:
      In the general population depression has a good immediate prognosis but a
      recurring nature. Poor physical health and low levels of social support appear to
      increase the risk of later episodes of depression. The influence of social risk
      factors may be greater for persons with higher susceptibility to depression.

PMID- 18083545
TI  - Underestimation of relative risks by standardized incidence ratios for AIDS
      related cancers.
AB  - PURPOSE: Registry-based studies provide valuable data regarding cancer risk among
      people with HIV/AIDS (PWHA). Such studies utilize the standardized incidence
      ratio (SIR) to estimate the relative risk (RR), an etiologically relevant
      measure. However, SIR may underestimate RR when HIV/AIDS prevalence in the
      general population or RR is high. We quantified the extent of this
      underestimation for 3 AIDS-related cancers: Kaposi sarcoma (KS), central nervous
      system non-Hodgkin lymphoma (CNS NHL) and cervical cancer. METHODS: We used data
      on cancer risk among PWHA from the U.S. HIV/AIDS Cancer Match Study. SIRs were
      compared with RRs estimated using two methods: (1) SIRs calculated using pre-AIDS
      era (1973-1979) cancer incidence rates (SIRpre-AIDS) and (2) SIRs calculated
      after subtraction of cancers known to be among PWHA from general population rates
      (SIRexclusion). RESULTS: For KS and CNS NHL, SIRs (117.8 and 133.9, respectively)
      calculated using overall general population rates substantially underestimated
      both SIRpre-AIDS (19,778 and 3,612, respectively) and SIRexclusion (657.7 and
      536.4, respectively). In contrast, the extent of underestimation was negligible
      for cervical cancer (SIR = 4.9 vs. SIRexclusion = 5.1). For KS and CNS NHL, SIRs
      were higher in females than in males. However, SIRpre-AIDS and SIRexclusion
      estimates were more similar, indicating that SIR differences artifactually
      reflect differences in HIV/AIDS prevalence between males and females. For KS and
      CNS NHL, trends across calendar time were weaker in SIRs than in SIRpre-AIDS and
      SIRexclusion. CONCLUSION: For KS and CNS NHL, SIRs substantially underestimate
      RRs. This underestimation arises from the exceptionally high relative risk of KS
      and CNS NHL among PWHA. SIRs must be interpreted cautiously when HIV/AIDS
      prevalence is high or varies across groups of interest.

PMID- 18083546
TI  - Obesity and adult asthma: potential effect modification by gender, but not by hay
      fever.
AB  - PURPOSE: First, we sought to estimate the magnitude of the cross-sectional
      associations between overweight/obesity and asthma stratified by gender and by
      self-reported hay fever and second we sought to assess both directions of
      causality in longitudinal analyses. METHODS: We used cross-sectional and
      longitudinal data from a population-based cohort study (n=5114, ages 40-65 at
      baseline). After 8.5 years, 4010 adults were followed-up by questionnaires. Self
      reported height and weight were used to calculate body mass index categories.
      Multivariate adjusted prevalence ratios (PRs), relative risks (RRs), and 95%
      confidence intervals (95% CI) were calculated using Poisson regression. RESULTS:
      In cross-sectional analyses, adjusted PRs were comparable for overweight women
      and men but differed between obese women and men (PR 1.93, 95% CI 1.19-3.14 and
      PR 0.98, 95% CI 0.56-1.72). PRs were similar when stratified by hay fever.
      Longitudinal analyses suggested that overweight/obesity did not increase asthma
      risk substantially (RR 1.02, 95% CI 0.50-2.06), but a relation between asthma and
      subsequent weight gain could not be excluded (RR 1.34, 95% CI 1.01-1.77).
      CONCLUSIONS: The prevalence of asthma is almost twice as high in obese versus
      normal weight women, but not in obese men. The association between
      overweight/obesity and asthma does not vary by hay fever. A causal relationship
      between asthma and incident weight gain cannot be excluded.

PMID- 18083547
TI  - Information disclosure in population-based research involving genetics: a
      framework for the practice of ethics in epidemiology.
AB  - PURPOSE: The completion of the Human Genome Project has resulted in increased
      epidemiological research to identify genes and their products as risk factors for
      adverse health events. A parallel increase in ethical issues associated with
      genetic research is noted. One such issue is whether or not epidemiologists
      should disclose individual genetic results to research participants. Existing
      ethical guidelines and frameworks are not helpful for determining whether
      disclosure is the moral choice. The purpose of this paper was to develop a
      framework for use by epidemiologists, research ethics boards, and institutional
      review boards during the protocol development stage to ethically address the
      dilemma regarding disclosure of individual genetic information. METHODS: The core
      principles of research ethics were introduced and applied to the issues
      surrounding disclosure of genetic information. A principle-based framework was
      developed through analysis of the current ethical arguments for and against
      disclosure. Finally, examples demonstrating the use of the framework were
      provided. CONCLUSION: The proposed framework will not solve all ethical dilemmas
      related to individual disclosure of genetic information. It is, however, a useful
      starting point to facilitate the consideration process.

PMID- 18083548
TI  - Influenza virus-specific cytotoxic T lymphocytes: a correlate of protection and a
      basis for vaccine development.
AB  - Since influenza A viruses of the H5N1 subtype continue to circulate in wild and
      domestic birds and cause an ever increasing number of human cases, it is feared
      that H5N1 viruses may cause the next influenza pandemic. Therefore, there is
      considerable interest in the development of vaccines that confer protection
      against infections with these viruses or ideally, protection against influenza
      viruses of different subtypes. For the development of broad-protective vaccines
      the induction of virus-specific cytotoxic T lymphocytes (CTL) may be an important
      target, since it has been demonstrated that CTL contribute to protective immunity
      and are largely directed to epitopes shared by influenza viruses of various
      subtypes. In the present paper, the possibility to develop (cross-reactive) CTL
      inducing vaccines is discussed.

PMID- 18083549
TI  - Virus-like particles-universal molecular toolboxes.
AB  - Virus-like particles (VLPs) are highly organised spheres that self-assemble from
      virus-derived structural antigens. These stable and versatile subviral particles
      possess excellent adjuvant properties capable of inducing innate and cognate
      immune responses. Commercialised VLP-based vaccines have been successful in
      protecting humans from hepatitis B virus (HBV) and human papillomavirus (HPV)
      infection and are currently explored for their potential to combat other
      infectious diseases and cancer. Much insight into VLP-mediated immune stimulation
      and optimised VLP design has been gained from human immunodeficiency virus (HIV)
      derived VLPs presenting promising components of current AIDS vaccine approaches.
      Owing to their unique features, VLPs and virosomes, the in vitro-reconstituted
      VLP counterparts, have recently gained ground in the field of nanobiotechnology
      as organic templates for the development of new biomaterials.

PMID- 18083550
TI  - Optimization of extraction of high-ester pectin from passion fruit peel
      (Passiflora edulis flavicarpa) with citric acid by using response surface
      methodology.
AB  - A central composite design was employed to optimize the extraction of pectin with
      citric acid. The independent variables were citric acid concentration (0.086
      2.91% w/v) and extraction time (17-102 min). The combined effect of these
      variables on the degree of esterification was investigated. Results have shown
      that the generated regression models adequately explained the data variation and
      significantly represented the actual relationship between the independent
      variables and the responses. Besides that, the citric acid concentration was the
      most important factor to affect the degree of esterification, as it exerted a
      significant influence on the dependent variable. Lower citric acid concentration
      increased the pectin degree of esterification. The surface response showed the
      relationships between the independent variables, and thus responses were
      generated. Through this surface, the satisfactory condition of 0.086% w/v citric
      acid for 60 min was established for extraction of high-ester yellow passion fruit
      pectin.

PMID- 18083551
TI  - Optimization of culture conditions for production of cis-epoxysuccinic acid
      hydrolase using response surface methodology.
AB  - Response surface methodology, which allows for rapid identification of important
      factors and optimization of them to enhance enzyme production, was employed here
      to optimize culture conditions for the production of cis-epoxysuccinic acid
      hydrolase from Bordetella sp. strain 1-3. In the first step, a Plackett-Burman
      design was used to evaluate the effects of nine variables (yeast extract, cis
      epoxysuccinic acid, KH(2)PO(4), K(2)HPO(4).3H(2)O, MgSO(4).7H(2)O, trace minerals
      solution, culture volume, initial pH and incubation time) on the enzyme
      production. Yeast extract, cis-epoxysuccinic acid and KH(2)PO(4) had significant
      influences on cis-epoxysuccinic acid hydrolase production and their
      concentrations were further optimized using central composite design and response
      surface analysis. A combination of adjusting the concentration of yeast extract
      to 7.8 g/l, cis-epoxysuccinic acid to 9.8 g/l, and KH(2)PO(4) to 1.12 g/l would
      favor maximum cis-epoxysuccinic acid hydrolase production. An enhancement of cis
      epoxysuccinic acid hydrolase production from 5.6 U/ml to 9.27 U/ml was gained
      after optimization.

PMID- 18083552
TI  - Down-regulation of defender against apoptotic death (DAD1) after yellow head
      virus (YHV) challenge in black tiger shrimp Penaeus monodon.
AB  - Here we describe the highly conserved gene, defender against apoptotic death
      (DAD1) identified from an EST library of the black tiger shrimp Penaeus monodon.
      The full-length cDNA of DAD1 of P. monodon comprised 638bp with an ORF of 345bp
      corresponding to 114 deduced amino acids. The deduced amino acid sequence was
      compared to known DAD1 sequences in the GenBank and in other databases.
      Phylogenetic analysis revealed that P. monodon DAD1 clustered with DAD1 from
      other invertebrates. Real-time RT-PCR with RNA extracts from normal P. monodon
      revealed DAD1 expression in several tissues including those of digestive and
      defense organs such as the hepatopancreas and hemocytes, respectively. If death
      from YHV infection was related to increased levels of apoptosis, we reasoned that
      the level of DAD1 should decrease as YHV infections progressed, especially in
      hemocytes (HC), one of its main targets. Real-time RT-PCR with RNA extracts from
      HC of P. monodon challenged with YHV revealed that the transcriptional level of
      DAD1 declined dramatically (approximately 50%) after YHV challenge. Although this
      suggests that DAD1 plays a role in mortality caused by YHV, control of apoptosis
      is complex and involves the interaction of many proteins, few of which have been
      characterized for shrimp. Thus, firm conclusions regarding the role of DAD1 must
      await the description and characterization of other proteins.

PMID- 18083553
TI  - Synthetic ligands that activate and inhibit a quorum-sensing regulator in
      Pseudomonas aeruginosa.
AB  - The transcription factor QscR is a regulator of quorum sensing in Pseudomonas
      aeruginosa and plays a role in controlling virulence in this prevalent
      opportunistic pathogen. This study outlines the discovery of a set of synthetic N
      acylated homoserine lactones that are capable of either activating or strongly
      inhibiting QscR in a cell-based reporter gene assay. We demonstrate that the
      synthetic antagonists inhibit ligand-dependent QscR binding to DNA. Several of
      these ligands can selectively modulate QscR instead of LasR, or modulate the
      activity of both receptors, and represent new chemical tools to study the
      hierarchy of quorum-sensing signaling in P. aeruginosa.

PMID- 18083554
TI  - N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective
      inhibitors of Lck: structure, synthesis and SAR.
AB  - N-3-(Phenylcarbamoyl)arylpyrimidine-5-carboxamides are a novel class of selective
      Lck inhibitors. This series of compounds derives its selectivity from a hydrogen
      bond with the gatekeeper Thr316 of the enzyme. X-ray co-crystal structural data,
      structure-activity relationships, and the synthesis of these inhibitors are
      reported herein.

PMID- 18083555
TI  - Conformational analyses of thiirane-based gelatinase inhibitors.
AB  - SB-3CT is a thiirane-containing inhibitor of the gelatinase class of matrix
      metalloprotease enzymes. In support of the mechanistic study of this inhibition,
      the conformational analyses of SB-3CT (and of two methyl-substituted derivatives)
      were undertaken using X-ray crystallography and molecular dynamics simulation.

PMID- 18083556
TI  - Inhibition of tubulin polymerization by select alkenyldiarylmethanes.
AB  - During studies on the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse
      transcriptase inhibitors (NNRTIs), analogues were discovered that exhibit low
      micromolar and submicromolar cytotoxicities. Since the ADAMs are structurally
      related to the tubulin polymerization inhibitor CC-5079, a set of 14 ADAMs were
      tested for inhibition of tubulin polymerization in an attempt to identify the
      biological target responsible for their cytotoxicity. The results indicate that,
      overall, the ADAMs are poor inhibitors of tubulin polymerization. However, the
      two most cytotoxic compounds, 15 and 16, are in fact active as inhibitors of
      tubulin assembly with IC(50) values of 3.7+/-0.3 and 2.8+/-0.2 microM,
      respectively, and they both inhibit the binding of colchicine to tubulin. Both
      compounds were investigated for anticancer activity in the National Cancer
      Institute's panel of 60 human cancer cell lines, and both compounds consistently
      displayed submicromolar cytotoxicities with mean-graph midpoint (MGM) values of
      0.31+/-0.08 and 0.47+/-0.09 microM, respectively.

PMID- 18083557
TI  - Protected aminooxyprolines for expedited library synthesis: application to Tsg101
      directed proline-oxime containing peptides.
AB  - The stereoselective synthesis of aminooxy-containing proline analogues bearing
      Fmoc/Boc or Fmoc/Mtt protection that renders them suitable for incorporation into
      peptides using Fmoc protocols is reported. Acid-catalyzed unmasking at the
      completion of peptide synthesis yields free aminooxy-functionalities for oxime
      formation through reaction with libraries of aldehydes. This allows post solid
      phase diversification strategies that may facilitate structure-activity
      relationship studies.

PMID- 18083558
TI  - beta-N-Biaryl ether sulfonamide hydroxamates as potent gelatinase inhibitors:
      part 2. Optimization of alpha-amino substituents.
AB  - The introduction and the optimization of an alpha-amino substituent based on a
      series of alpha-hydroxy-beta-N-biaryl ether sulfonamide hydroxamates is
      described. The modification leads to a new series of MMP-2/MMP-9 inhibitors with
      enhanced inhibitory activities and improved ADME properties. An efficacy study on
      reducing the ischemia-induced brain edema in the rat transient middle cerebral
      artery occlusion (tMCAo) model is also demonstrated.

PMID- 18083559
TI  - Binding free energy calculation for duocarmycin/DNA complex based on the QPLD
      derived partial charge model.
AB  - The 3ns unrestrained MD simulations were carried out on the DNA/duocarmycin
      complex based on (1) the classic RESP charge model, and (2) the QM-polarized
      ligand docking (QPLD)-based charge model. The RMSDs of the trajectories and the
      DeltaG(bind) of the QPLD model perform much better than the RESP model, with the
      DeltaG(bind) estimation for QPLD model (-16.11 kcal/mol) versus DeltaG(bind)
      estimation for RESP model (-10.05 kcal/mol).

PMID- 18083560
TI  - Discovery of a novel class of selective human CB1 inverse agonists.
AB  - Ligand-based virtual screening led to the discovery of a new class of potent
      inverse agonists of the human cannabinoid receptor 1, hCB(1), which are selective
      versus hCB(2). These CB(1) ligands present intriguing departures from a classical
      CB(1) antagonist pharmacophore. Elements of SAR are discussed in this context.

PMID- 18083561
TI  - Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase
      inhibitors (NNRTIs).
AB  - This Letter describes the design, synthesis, and biological evaluation of novel 3
      indole sulfonamides as potent non-nucleoside reverse transcriptase inhibitors
      (NNRTIs) with balanced profiles against common HIV RT mutants K103N and Y181C.

PMID- 18083562
TI  - Prodrug thiamine analogs as inhibitors of the enzyme transketolase.
AB  - Transketolase, a key enzyme in the pentose phosphate pathway, has been suggested
      as a target for inhibition in the treatment of cancer. Compound 5a ('N3'-pyridyl
      thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl
      thiazol-3-ium chloride hydrochloride), an analog of the transketolase cofactor
      thiamine, is a potent transketolase inhibitor but suffers from poor
      pharmacokinetics due to high clearance and C(max) linked toxicity. An efficient
      way of improving the pharmacokinetic profile of 5a is to prepare oxidized
      prodrugs which are slowly reduced in vivo yielding longer, sustained blood levels
      of the drug. The synthesis of such prodrugs and their evaluation in rodent models
      is reported.

PMID- 18083563
TI  - Experimental and modeling investigation of spectral compression of biceps brachii
      SEMG activity with increasing force levels.
AB  - This study investigated possible motor unit (MU) firing patterns underlying
      changes in biceps brachii (BB) surface electromyographic (SEMG) activity in 96
      participants who performed isometric actions of the elbow flexors at 40%, 60%,
      80%, and 100% of maximum voluntary contraction (MVC). We also conducted a
      modeling investigation to determine the extent to which a model would fit the
      experimental results. Experimentally, there was a linear increase (277%; p<0.01)
      in root-mean-square (RMS) amplitude with increasing force. The mean power
      frequency (MNF) remained stable from 40% to 80% of MVC, but there was a decrease
      (8.2%; p<0.01) between 80% and 100% of MVC. A modeling approach was taken wherein
      well-known recruitment and rate-coding schemes activated MUs whose basic building
      block was the muscle fibre action potential. Two conditions were investigated:
      (1) an increase in firing rate (rate-coding) and (2) synchronization. The levels
      of rate-coding and synchronization were selected to produce a linear RMS-force
      relationship as observed in the experimental data. Then, the impact of these two
      strategies on changes in MNF was assessed. The MNF remained stable from 40% to
      80% of maximum excitation for both the rate-coding and synchronization
      conditions. There was a decrease in MNF between 80% and 100% of maximum
      excitation for both modeling conditions, similar to that observed for the
      experimental data. Thus, at these high forces at which experimental data are
      technically difficult to obtain, the model supports the idea that both rate
      coding and synchronization are responsible for the changes observed in surface
      EMG amplitude and frequency characteristics.

PMID- 18083564
TI  - Human face preference in gamma-frequency EEG activity.
AB  - Previous studies demonstrated that induced EEG activity in the gamma band (iGBA)
      plays an important role in object recognition and is modulated by stimulus
      familiarity and its compatibility with pre-existent representations. In the
      present study we investigated the modulation of iGBA by the degree of familiarity
      and perceptual expertise that observers have with stimuli from different
      categories. Specifically, we compared iGBA in response to human faces versus
      stimuli which subjects are not expert with (ape faces, human hands, buildings and
      watches). iGBA elicited by human faces was higher and peaked earlier than that
      elicited by all other categories, which did not differ significantly from each
      other. These findings can be accounted for by two characteristics of perceptual
      expertise. One is the activation of a richer, stronger and, therefore, more
      easily accessible mental representation of human faces. The second is the more
      detailed perceptual processing necessary for within-category distinctions, which
      is the hallmark of perceptual expertise. In addition, the sensitivity of iGBA to
      human but not ape faces was contrasted with the face-sensitive N170-effect, which
      was similar for human and ape faces. In concert with previous studies, this
      dissociation suggests a multi-level neuronal model of face recognition,
      manifested by these two electrophysiological measures, discussed in this paper.

PMID- 18083565
TI  - The intrinsic functional organization of the brain is altered in autism.
AB  - In higher functioning individuals with autism, a striking disparity exists
      between impaired social and emotional abilities and relatively preserved
      sustained attention and goal-directed cognitive abilities. As these two
      functional domains appear to map onto two distinct large-scale brain networks,
      the Task-Negative Network and the Task-Positive Network, respectively, we
      examined their intrinsically defined functional organization in individuals with
      autism. Using resting functional connectivity MRI (fcMRI), we found that, in
      autism, there was altered functional organization of the network involved in
      social and emotional processing, but no group difference in the functional
      organization of the network involved in sustained attention and goal-directed
      cognition. We suggest that these findings might serve to relate the seemingly
      disparate strengths and weaknesses of the autistic behavioral, perceptual, and
      cognitive phenotype into a tractable neurofunctional framework. These results
      also highlight the usefulness of resting fcMRI for studying the brain in
      neuropsychiatric and neurodevelopmental disorders.

PMID- 18083566
TI  - Topodiagnostic implications of hemiataxia: an MRI-based brainstem mapping
      analysis.
AB  - The topodiagnostic implications of hemiataxia following lesions of the human
      brainstem are only incompletely understood. We performed a voxel-based
      statistical analysis of lesions documented on standardised MRI in 49
      prospectively recruited patients with acute hemiataxia due to isolated unilateral
      brainstem infarction. For statistical analysis individual MRI lesions were
      normalised and imported in a three-dimensional voxel-based anatomical model of
      the human brainstem. Statistical analysis revealed hemiataxia to be associated
      with lesions of three distinct brainstem areas. The strongest correlation
      referred to ipsilateral rostral and dorsolateral medullary infarcts affecting the
      inferior cerebellar peduncle, and the dorsal and ventral spinocerebellar tracts.
      Secondly, lesions of the ventral pontine base resulted in contralateral limb
      ataxia, especially when ataxia was accompanied by motor hemiparesis. In patients
      with bilateral hemiataxia, lesions were located in a paramedian region between
      the upper pons and lower midbrain, involving the decussation of dentato-rubro
      thalamic tracts. We conclude that ataxia following brainstem infarction may
      reflect three different pathophysiological mechanisms. (1) Ipsilateral hemiataxia
      following dorsolateral medullary infarctions results from a lesion of the dorsal
      spinocerebellar tract and the inferior cerebellar peduncle conveying afferent
      information from the ipsilateral arm and leg. (2) Pontine lesions cause
      contralateral and not bilateral ataxia presumably due to major damage to the
      descending corticopontine projections and pontine base nuclei, while already
      crossed pontocerebellar fibres are not completely interrupted. (3) Finally,
      bilateral ataxia probably reflects a lesion of cerebellar outflow on a central,
      rostral pontomesencephalic level.

PMID- 18083567
TI  - Atypical ductal hyperplasia: a way to minimize underestimation in vacuum-assisted
      breast biopsy?

PMID- 18083568
TI  - Pili in Gram-positive bacteria: assembly, involvement in colonization and biofilm
      development.
AB  - Various cell-surface multisubunit protein polymers, known as pili or fimbriae,
      have a pivotal role in the colonization of specific host tissues by many
      pathogenic bacteria. In contrast to Gram-negative bacteria, Gram-positive
      bacteria assemble pili by a distinct mechanism involving a transpeptidase called
      sortase. Sortase crosslinks individual pilin monomers and ultimately joins the
      resulting covalent polymer to the cell-wall peptidoglycan. Here we review current
      knowledge of this mechanism and the roles of Gram-positive pili in the
      colonization of specific host tissues, modulation of host immune responses and
      the development of bacterial biofilms.

PMID- 18083569
TI  - Microbiological contamination in cell culture: a potential role for hydrogen
      peroxide vapour (HPV)?

PMID- 18083570
TI  - Alternatively spliced forms of the P180 ribosome receptor differ in their ability
      to induce the proliferation of rough endoplasmic reticulum.
AB  - Expression of the canine 180-kDa ribosome receptor p180 in yeast induces the
      synthesis of RER, and increases the mRNAs of secretory pathway proteins, and
      protein secretion. To assess whether p180 is a master regulator of cell secretion
      in mammalian cells, we stably expressed red fluorescent forms of the human p180
      variants p180DeltaR (no tandem repeats), p180R (26 repeats), and full-length
      p180FR (54 repeats) containing different lengths of the tandem repeat ribosome
      binding domain in rat pancreatic RINm5F islet beta-cells. All three fluorescent
      p180 variants localized exclusively to the RER. Cells transfected with p180R were
      filled with ribosome-studded karmellae, whereas p180DeltaR and p180FR
      transfectants contained only increased amounts of mostly smooth ER. Unlike in
      yeast, over-expression of p180R failed to increase the secretory pathway proteins
      calnexin, SEC61beta, and calreticulin, or ribosome biogenesis. The data suggest
      that alternative splicing of the p180 tandem repeat domain is a means of
      regulating the ribosome-binding activity of p180, and potentially the secretory
      activity of the cell. However, p180 is not a master regulator of mammalian cell
      secretion as it does not concomitantly trigger the synthesis of protein machinery
      required to enhance protein synthesis and cell secretion.

PMID- 18083571
TI  - Anticoagulant usage for primary stroke prevention: a general practitioner survey
      in local areas of metropolitan Sydney.
AB  - We assessed the hypothesis that having a non-English-speaking background (NESB),
      being very elderly, living alone, and having cognitive impairment were
      contributing factors to anticoagulant under-utilisation for atrial fibrillation
      in our local community. A questionnaire was mailed to 532 general practitioners
      (GPs) in three areas of metropolitan Sydney, Australia. The questionnaire
      included five case scenarios, regarding either an English-speaking background
      (ESB) patient, or an NESB patient, each characterised by potential barrier(s) for
      anticoagulant usage: being (1) elderly; (2) elderly with mild dementia; (3)
      elderly with mild dementia and living alone; (4) elderly with severe dementia;
      and (5) very elderly. The overall response rate was 34%. The percentage of GPs
      recommending anticoagulation was 57%, 50%, 6%, 25% and 23%, respectively, for the
      ESB scenario, and 48%, 32%, 4%, 14% and 18%, respectively, for the NESB scenario.
      Eighty-eight percent of GPs rated 'adherence to International Normalized Ration
      monitoring' as 'very important' in their decision. In conclusion, the factors
      proposed in our hypothesis were associated with a lower likelihood for
      anticoagulant prescription for atrial fibrillation.

PMID- 18083572
TI  - Results of a phase I dendritic cell vaccine trial for malignant astrocytoma:
      potential interaction with adjuvant chemotherapy.
AB  - Dendritic cell vaccination has been applied to the treatment of a variety of
      cancers, including malignant astrocytoma. We have treated 13 patients with
      malignant astrocytoma using dendritic cell vaccination and have shown that this
      treatment is safe and is likely to be effective in combination with standard
      adjuvant therapy. Future studies should prospectively incorporate dendritic cell
      vaccination together with chemotherapy. Ideally, dendritic cell vaccination
      should be tested in a prospective fashion, in a coordinated trial involving
      multiple centres.

PMID- 18083573
TI  - Interdural cavernous sinus epidermoid cyst.
AB  - We report a patient with an uncommon interdural epidermoid tumor, located within
      the confines of dural layers of the lateral wall of the cavernous sinus. The
      tumor was resected by a basal subtemporal extradural-interdural approach.
      Following the surgery, the 45-year-old female patient recovered completely from
      her symptoms of atypical neuralgic facial pains.

PMID- 18083574
TI  - Structures of an MHC class I molecule from B21 chickens illustrate promiscuous
      peptide binding.
AB  - Little is known about the structure of major histocompatibility complex (MHC)
      molecules outside of mammals. Only one class I molecule in the chicken MHC is
      highly expressed, leading to strong genetic associations with infectious
      pathogens. Here, we report two structures of the MHC class I molecule BF2*2101
      from the B21 haplotype, which is known to confer resistance to Marek's disease
      caused by an oncogenic herpesvirus. The binding groove has an unusually large
      central cavity, which confers substantial conformational flexibility to the
      crucial residue Arg9, allowing remodeling of key peptide-binding sites. The
      coupled variation of anchor residues from the peptide, utilizing a charge
      transfer system unprecedented in MHC molecules, allows peptides with
      conspicuously different sequences to be bound. This promiscuous binding extends
      our understanding of ways in which MHC class I molecules can present peptides to
      the immune system and might explain the resistance of the B21 haplotype to
      Marek's disease.

PMID- 18083575
TI  - Structures of T cell immunoglobulin mucin protein 4 show a metal-Ion-dependent
      ligand binding site where phosphatidylserine binds.
AB  - The T cell immunoglobulin and mucin domain (TIM) proteins are important
      regulators of T cell responses. Crystal structures of the murine TIM-4 identified
      a metal-ion-dependent ligand binding site (MILIBS) in the immunoglobulin (Ig)
      domain of the TIM family. The characteristic CC' loop of the TIM domain and the
      hydrophobic FG loop shaped a narrow cavity where acidic compounds penetrate and
      coordinate to a metal ion bound to conserved residues in the TIM proteins. The
      structure of phosphatidylserine bound to the Ig domain showed that the
      hydrophilic head penetrates into the MILIBS and coordinates with the metal ion,
      whereas the aromatic residues on the tip of the FG loop interacted with the fatty
      acid chains and could insert into the lipid bilayer. Our results also revealed an
      important role of the MILIBS in the trafficking of TIM-1 to the cell surface.

PMID- 18083576
TI  - The heterodimeric assembly of the CD94-NKG2 receptor family and implications for
      human leukocyte antigen-E recognition.
AB  - The CD94-NKG2 receptor family that regulates NK and T cells is unique among the
      lectin-like receptors encoded within the natural killer cell complex. The
      function of the CD94-NKG2 receptors is dictated by the pairing of the invariant
      CD94 polypeptide with specific NKG2 isoforms to form a family of functionally
      distinct heterodimeric receptors. However, the structural basis for this
      selective pairing and how they interact with their ligand, HLA-E, is unknown. We
      describe the 2.5 A resolution crystal structure of CD94-NKG2A in which the mode
      of dimerization contrasts with that of other homodimeric NK receptors. Despite
      structural homology between the CD94 and NKG2A subunits, the dimer interface is
      asymmetric, thereby providing a structural basis for the preferred heterodimeric
      assembly. Structure-based sequence comparisons of other CD94-NKG2 family members,
      combined with extensive mutagenesis studies on HLA-E and CD94-NKG2A, allows a
      model of the interaction between CD94-NKG2A and HLA-E to be established, in which
      the invariant CD94 chain plays a more dominant role in interacting with HLA-E in
      comparison to the variable NKG2 chain.

PMID- 18083577
TI  - Entry route of Salmonella typhimurium directs the type of induced immune
      response.
AB  - Secretory immunoglobulin A (SIgA) represents a first line of defense against
      mucosal pathogens by limiting their entrance. By using different strains of
      Salmonella typhimurium that target the two mechanisms of bacterial entry
      (microfold cell [M cell]- or dendritic cell-mediated), we demonstrated here that
      the distribution of bacteria after oral infection directed the type of induced
      immune response. M cell-penetrating invasive, but not noninvasive, S. typhimurium
      was found in large numbers in Peyer's patches (PPs), leading to the activation of
      immune cells and the release of fecal IgA. In contrast, both strains of bacteria
      were equally capable of reaching the mesenteric lymph node and the spleen and
      inducing IgG responses. These data suggest that PPs are absolutely required for
      the initiation of an IgA response to Salmonella, whereas they are dispensable for
      a systemic response. This compartmentalization could allow the fast generation of
      both mucosal and systemic acquired immunity to pathogens.

PMID- 18083578
TI  - Stereospecific synthesis and bio-activity of novel beta(3)-adrenoceptor agonists
      and inverse agonists.
AB  - Since it is widely distributed into the body, beta(3)-adrenoceptor is becoming an
      attractive target for the treatment of several pathologies such as obesity, type
      2 diabetes, metabolic syndrome, cachexia, overactive bladder, ulcero-inflammatory
      disorder of the gut, preterm labour, anxiety and depressive disorders, and heart
      failure. New compounds belonging to the class of arylethanolamines bearing one or
      two stereogenic centres were prepared in good yields as racemates and optically
      active forms. They were, then, evaluated for their intrinsic activity towards
      beta(3)-adrenoceptor and their affinity for beta(1)- and beta(2)-adrenergic
      receptors. Stereochemical features were found to play a crucial role in
      determining the behaviour of such compounds. In particular, alpha-racemic,
      (alphaR)- and (alphaS)-2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}-2-
      methylpropanoic acid, (alpha-rac, beta-rac)-, (alphaR, betaS)- and (alphaR,
      betaR)- 2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}propanoic acid were
      found to be endowed with beta(3)-adrenoceptor agonistic activity. Whereas,
      (alphaS, betaS)- and (alphaS, betaR)-2-{4-[2-(2-hydroxy-2
      phenylethylamino)ethyl]phenoxy}propanoic acid behaved as beta(3)-adrenoceptor
      inverse agonists. Such compounds showed no affinity for beta(1)- and beta(2)
      adrenergic receptor, respectively. Thus, resulting highly selective beta(3)
      adrenoceptor ligands.

PMID- 18083579
TI  - Synthesis and structure-activity relationships of a series of benzazepine
      derivatives as 5-HT2C receptor agonists.
AB  - To identify potent and selective 5-HT(2C) receptor agonists, a series of novel
      benzazepine derivatives were synthesized, and their structure-activity
      relationships examined. The compounds were evaluated for their 5-HT(2C), 5
      HT(2A), and 5-HT(2B) receptor binding affinity and intrinsic activity for the 5
      HT(2C) and 5-HT(2A) receptors. Among these compounds, 6,7-dichloro-2,3,4,5
      tetrahydro-1H-3-benzazepine (6) was effective in a rat penile erection model when
      administered po, which is a symptom of the serotonin syndrome reflecting 5-HT(2C)
      receptor activation. Moreover, compound 6 was characterized as a partial agonist
      of 5-HT(2A) receptors; therefore, it had little effect on the cardiovascular
      system.

PMID- 18083580
TI  - Novel quinazolinone derivatives as 5-HT7 receptor ligands.
AB  - 5-HT(7) receptor antagonists generated antidepressant-like effects in animal
      model and the involvement of the 5-HT(7) receptor in other pathophysiological
      mechanisms such as thermoregulation, learning and memory, and sleep has been
      highlighted by various studies. As one of our efforts to discover a new type of 5
      HT(7) receptor antagonists, we here report on the synthesis and binding
      affinities to the 5-HT(7) receptor of the quinazolinone library 1, which was
      designed with various substituents (X, Y, R(1), and R(2)) on the aromatic rings
      and different carbon chain length. Total 85 compounds of the quinazolinone
      library 1 were synthesized and the binding affinities of all the synthesized
      compounds were obtained by radioligand binding assay for the 5-HT(7) receptor.
      Among the 85 compounds, 24 compounds show very good binding affinities with
      IC(50) values below 100 nM. Mainly the compounds with IC(50) values below 100 nM
      have o-OMe or o-OEt as R(2) substituent. The compound with the best binding
      affinity is 1-68 of which the IC(50) value is 12 nM. In in vivo animal study,
      some synthesized compounds really have the antidepressant activity in the forced
      swimming test in mice.

PMID- 18083581
TI  - Elective abdominal aortic aneurysm repair: does the aneurysm diameter influence
      long-term survival?
AB  - OBJECTIVES: The aim of this study was to investigate whether initial abdominal
      aortic aneurysm (AAA) diameter influences long-term survival after elective
      repair. DESIGN: Retrospective analysis of database. MATERIAL AND METHODS: Between
      March 1995 and December 2006, a consecutive series of 895 patients underwent
      elective treatment of an AAA either by open surgical or endovascular repair. An
      AAA diameter of 5.5cm was chosen as threshold to distinguish between small and
      large aneurysms, according to the definition given by the UK small aneurysm
      trial. Patient characteristics and distribution of basic risk factors were
      assessed. Survival estimates (Kaplan-Meier) and Cox proportional hazards
      regression results are reported. RESULTS: Patients with small aneurysms were more
      likely to survive the first 6 years after AAA repair, even after adjustment for
      treatment modality and baseline risk factors. After adjustment for age and sex
      aneurysms with smaller diameter were related to a lower risk of death (p<0.0016).
      CONCLUSIONS: Patients with small aneurysms (< or =5.5cm) have an improved long
      term survival than patients with larger aneurysms.

PMID- 18083582
TI  - High-resolution single-particle 3D analysis on GroEL prepared by cryo-negative
      staining.
AB  - Cryo-negative staining was developed as a complementary technique to conventional
      cryo-electron microscopy on supramolecular complexes. It allows imaging
      biological samples in a comparable state of structural preservation to
      conventional cryo-EM but the staining produces better contrast in accessible
      areas and allows data recording at lower defocus values. Cryo-negative staining
      vitrifies biological particles in the presence of a concentrated ammonium
      molybdate solution at neutral pH. It was successfully used to study the structure
      and dynamics of several macromolecules, such as human transcription factors and
      RNA polymerases. Imaging macromolecular complexes with cryo-negative staining has
      been established previously to better than 2 nm detail. However, it has not been
      verified so far whether cryo-negative staining also visualizes secondary
      structure elements. Using the well known E. coli GroEL chaperonin, we could show
      that the structure is well preserved to approximately 10 A resolution. Secondary
      structure details are at least partially resolved in the electron density map.

PMID- 18083583
TI  - Molecular epidemiology of Cryptosporidium subtypes in cattle in England.
AB  - Samples of Cryptosporidium spp., collected in a cross-sectional study of calves
      (median age 26 days) from 41 farms in Cheshire, UK, underwent molecular typing.
      The aim was to determine naturally occurring species/genotypes and to investigate
      transmission pathways within a local area. Of 60 positive samples, 54 were
      sequenced at an 18S rRNA locus and 51 were typed at a GP60 locus. C. parvum was
      identified in 50 samples, three cases were C. bovis and one was Cryptosporidium
      deer-like genotype. Six GP60 subgenotypes were identified. One subgenotype
      (IIaA15G2R1) was highly prevalent throughout the study area. A single subgenotype
      was identified on 20/22 farms. Two subgenotypes were found on 2/22 farms. The
      spatial scan statistic detected a cluster of subgenotype IIaA15G2R1 comprising
      seven farms. This suggests local transmission of the parasite between farms. As
      most of the isolates detected were the potentially zoonotic C. parvum allele IIa,
      intervention strategies should be considered to reduce the threat to public
      health. Biosecurity measures may reduce transmission between farms and result in
      lower levels of environmental contamination.

PMID- 18083585
TI  - Sensory results after lateral rectus muscle recession for intermittent exotropia
      operated before two years of age.
AB  - INTRODUCTION: Early surgical treatment of early-onset intermittent exotropia is
      controversial. The condition does not always progress, and postoperative
      esotropia can produce adverse consequences, such as suppression, amblyopia, and
      loss of binocular vision, particularly stereopsis. It is not known whether
      surgery before age two years affects the sensory outcome. METHODS: Using a
      noncomparative (nonrandomized, uncontrolled) interventional case series, we
      reviewed the medical records during a 14-year period of 24 patients with
      intermittent exotropia with onset before age 1 year who also received bilateral
      lateral rectus muscle recessions before two years of age. Twelve patients were
      identified who received follow-up examinations at ages > or =4 years, when
      testing with Worth 4-Dot and Titmus stereo circles would likely be reliable.
      RESULTS: Mean age of the patients at last follow-up examination was 87 months.
      Stereoacuity was measured at 40 arcsec in 2 patients, 100 arcsec in 3 patients,
      140-400 arcsec in 2 patients, and none in 5 patients. Among the 5 patients
      without demonstrated stereopsis, 1 had a history and clinical course consistent
      with congenital exotropia, and 1 had a nonstrabismic explanation for poor
      stereopsis. Overall, 7 patients (58%) ultimately obtained favorable motor
      alignment, defined as a phoria or intermittent tropia <10(Delta) at distance and
      near. No patient required treatment for amblyopia. CONCLUSIONS: Early-onset
      intermittent exotropia usually responds well to surgical treatment, and high
      grade stereopsis can be achieved in some cases. More than one clinical entity
      presenting as intermittent exotropia in infancy probably exists.

PMID- 18083584
TI  - Which electrospray-based ionization method best reflects protein-ligand
      interactions found in solution? a comparison of ESI, nanoESI, and ESSI for the
      determination of dissociation constants with mass spectrometry.
AB  - We present a comparison of three different electrospray-based ionization
      techniques for the investigation of noncovalent complexes with mass spectrometry.
      The features and characteristics of standard electrospray ionization (ESI), chip
      based nanoESI, and electrosonic spray ionization (ESSI) mounted onto a hybrid
      quadrupole time-of-flight mass spectrometer were compared in their performance to
      determine the dissociation constant (KD) of the model system hen egg white
      lysozyme (HEWL) binding to N,N',N''-triacetylchitotriose (NAG3). The best KD
      value compared with solution data were found for ESSI, 19.4 +/- 3.6 microM. Then,
      we determined the KDs of the two nucleotide binding sites of adenylate kinase
      (AK), where we obtained KDs of 2.2 +/- 0.8 microM for the first and 19.5 +/- 8.0
      microM for the second binding site using ESSI. We found a weak charge state
      dependence of the KD for both protein-ligand systems, where for all ionization
      techniques the KD value decreases with increasing charge state. We demonstrate
      that ESSI is very gentle and insensitive to instrumental parameters, and the KD
      obtained is in good agreement with solution phase results from the literature. In
      addition, we tried to determine the KD for the lymphocyte-specific kinase LCK
      binding to a kinase inhibitor using nanoESI due to the very low amount of sample
      available. In this case, we found KD values with a strong charge state
      dependence, which were in no case close to literature values for solution phase.

PMID- 18083586
TI  - Optic nerve axon number in mouse is regulated by PAX2.
AB  - BACKGROUND: Papillorenal syndrome is an autosomal-dominant disease caused by
      mutations in the PAX2 transcription factor gene. Patients often exhibit
      congenital excavation of the optic nerve and a spectrum of congenital kidney
      abnormalities. Using a novel mouse model of this syndrome (C57BL/6J
      PAX2(A220G/+)), we investigated the effect of PAX2 haploinsufficiency on optic
      nerve axon number. Because PAX2 expression and retinal pigment epithelium
      pigmentation have a mutually exclusive relationship during development and
      because tyrosinase (Tyr) has been shown to modify the penetrance of other ocular
      development genes, we also investigated whether tyrosinase modified the mutant
      PAX2 phenotype. METHODS: C57BL/6J PAX2(A220G/+)Tyr(+/+) mice were crossed with
      mice of the same genetic background (C57BL/6J) that are homozygous for an
      effective null allele of tyrosinase (Tyr(c-2J/c-2J)) over two generations to
      create mice with four distinct genotypes: PAX2(A220G/+) Tyr(+/c-2J),
      PAX2(A220G/+) Tyr(c-2J/c-2J), PAX2(+/+) Tyr(c-2J/+), and PAX2(+/+)Tyr(c-2J/c-2J).
      Mouse optic nerves were examined clinically and histologically. Axon number was
      assessed in a masked fashion in optic nerves from mice of all four genotypes and
      compared with parental strains. RESULTS: Mice heterozygous for a PAX2 mutation
      show reduced optic nerve axon number compared with age-matched controls.
      Tyrosinase does not appear to modify this phenotype. CONCLUSIONS: Our results
      show that PAX2 is important in determining axon number in mouse optic nerve. The
      developmental effects of tyrosinase and PAX2 mutation appear to act via different
      pathways.

PMID- 18083587
TI  - Ocular involvement as the initial manifestation of Wegener's granulomatosis in
      children.
AB  - Ophthalmic manifestations are noted in about 50% of adults with Wegener's
      granulomatosis. Wegener's granulomatosis is a rare disease in the pediatric age
      group. The disease may present initially with ocular manifestations. We report
      the largest series to date of children whose ocular findings were the initial
      presenting signs of Wegener's granulomatosis.

PMID- 18083588
TI  - Resolution of childhood recurrent corneal phlyctenulosis following eradication of
      an intestinal parasite.
AB  - Phlyctenular keratoconjunctivitis is a nodular foreign antigen delayed
      hypersensitivity reaction typically due to staphylococcal protein (but
      potentially secondary to antigen from a variety of different organisms, eg,
      mycobacteria and intestinal worms).(1-4) Conjunctival phlyctens are usually mild
      and transient, but corneal phlyctens can be severe and recurrent.(3,4) The
      subject of this report is a severe recurrent unilateral corneal case in a child
      whose stool was positive for Hymenolepsis nana. Following treatment for the
      intestinal parasite, the child no longer suffered from recurrent ocular surface
      inflammation.

PMID- 18083589
TI  - Late vitreous hemorrhage in patients with regressed retinopathy of prematurity.
AB  - PURPOSE: To describe the characteristics of eyes with late vitreous hemorrhage in
      children with a history of regressed retinopathy of prematurity (ROP). METHODS:
      The medical records of consecutive patients with regressed ROP presenting to our
      institution with late vitreous hemorrhage between 1995 and 2006 were reviewed.
      RESULTS: Thirteen patients (14 eyes) were identified. All patients had stage 3 or
      higher ROP. Prior treatments included cryotherapy in three eyes, laser ablation
      in eight eyes, and laser followed by vitrectomy for retinal detachment in two
      eyes. Three eyes had had no prior ocular surgery. Age at late vitreous hemorrhage
      ranged from 10.8 months to 15 years (mean, 8.4 years). At the time of late
      vitreous hemorrhage, no eyes had active neovascularization, three eyes had a
      history of trauma, and three eyes had concurrent retinal detachment; eight eyes
      were observed (57%) and six (43%) were treated with vitrectomy. CONCLUSIONS: Late
      vitreous hemorrhage can occur in patients with regressed ROP years after the
      vascularly active phase of the disease. It likely results from abnormal
      vitreoretinal traction on otherwise normal retinal vessels or from a normal
      amount of traction on residual cicatricial tissue. Vitreous hemorrhage may occur
      in the absence of trauma, retinal tears, retinal detachment, or active
      neovascularization. With appropriate management, most patients maintained their
      baseline vision.

PMID- 18083590
TI  - Long-term follow-up of visual functions in prematurely born children--a
      prospective population-based study up to 10 years of age.
AB  - INTRODUCTION: Prematurely born children have an increased risk of ophthalmologic
      problems. There is still no consensus on how they should be followed. The purpose
      of this study was to evaluate predictive factors for problems in premature
      children at ten years of age and to discuss follow-up recommendations. MATERIALS
      AND METHODS: One hundred ninety-nine children with a birth weight of 1500 g or
      less were screened for retinopathy of prematurity (ROP) in the neonatal period
      and thereafter ophthalmologically examined at 6 months, 1.5, 2.5, 3.5, and 10
      years of age. "Visual dysfunction" at ten years of age was defined as visual
      acuity > or =0.1 logMAR and/or strabismus and/or subnormal contrast sensitivity.
      Multiple regression analyses were used to evaluate risk factors at an early age,
      which could predict problems at ten years of age. RESULTS: Twenty-five percent of
      the cohort had visual dysfunction at ten years of age. Neurological
      complications, cryotreated ROP, anisometropia, and astigmatism were risk factors.
      The sensitivity was 75.5%, and the specificity 80.7% for the detection of visual
      dysfunction at ten years of age when all children with neurological
      complications, cryotreated ROP, strabismus, anisometropia > or =1 diopters (D) at
      2.5 years, and astigmatism > or =2 D at 2.5 years were included in further follow
      up. CONCLUSIONS: Repeated ophthalmologic follow-up of prematurely born children
      should be performed in those with treated ROP and/or neurological conditions. For
      a third group without such problems, at least one follow-up is recommended. Such
      an examination also provides a good opportunity to identify neurological problems
      that warrant further ophthalmologic follow-up.

PMID- 18083591
TI  - Ophthalmic features of ataxia telangiectasia-like disorder.
AB  - INTRODUCTION: Ataxia telangiectasia (AT) is a recessive neurodegenerative disease
      due to a faulty repair mechanism for breaks in double-stranded DNA (ATM
      mutation). Ophthalmic features of AT include conjunctival telangiectasia,
      strabismus, saccadic dysfunction with head thrusts, and convergence
      insufficiency. Ataxia telangiectasia-like syndrome (ATLD) is a more recently
      recognized condition due to homozygous mutation in MRE11, a gene also involved in
      the cellular repair response to double-stranded DNA breaks; ophthalmic features
      of ATLD are not well described. The purpose of this article is to describe the
      ophthalmic features of ATLD. METHODS: Full ophthalmologic and orthoptic
      evaluations were obtained in 13 individuals: 10 previously reported ATLD
      patients, an additional related ATLD patient, and 3 nonaffected relatives. All
      individuals were from three unrelated consanguineous Saudi Arabian families
      harboring an MRE11 mutation (W210C). Age range was from 2 to 40 years of age.
      RESULTS: No affected patient had structural ocular abnormality (eg, conjunctival
      telangiectasia), manifest strabismus at distance, or duction limitation. All but
      one (the youngest) had saccadic dysfunction (without head thrusts). Most patients
      had abnormal convergence. Older patients had nystagmus with abnormalities in
      smooth pursuit and vestibular ocular reflex. All patients had cerebellar atrophy
      by neuroimaging and slowly progressive ataxia. The unaffected heterozygous
      relatives had unremarkable ophthalmic and neurologic examinations. CONCLUSIONS:
      Saccadic dysfunction without head thrusts and convergence abnormality are common
      in ATLD secondary to homozygous W210C MRE11 mutation. Older patients have
      nystagmus with abnormalities in smooth pursuit and vestibular ocular reflex. Eye
      movement control systems apparently deteriorate with time in this rare
      neurological disease. Ophthalmic features of AT that were not observed in any of
      our ATLD patients include conjunctival telangiectasia, head thrusting, and
      manifest strabismus at distance.

PMID- 18083592
TI  - Bilateral orbito-palpebral cysts in a case of cryptophthalmos associated with
      Fraser syndrome.
AB  - A 15-month-old girl was referred for evaluation of congenital absence of both
      eyelids. Clinical evaluation revealed bilateral total cryptophthalmos and
      enlarged globes in addition to genitourinary anomalies, umbilical hernia, renal
      agenesis, and facial anomalies. The clinical findings were consistent with Fraser
      syndrome. Magnetic resonance imaging of the orbits revealed dysplastic globes
      that were characterized by cystic expansions that extended laterally anterior to
      the lateral orbital rim. Bilateral orbito-palpebral cysts that communicate with a
      dysplastic globe and extend beyond the orbital cavity may be a rare presenting
      feature of Fraser syndrome.

PMID- 18083593
TI  - Improvement in motor development following surgery for infantile esotropia.
AB  - PURPOSE: Infantile esotropia is associated with abnormal visual development and
      thus may delay the achievement of developmental milestones. Although early
      surgery can improve visual function, less is known about its effect on motor
      development. Here we address whether early surgery can improve motor development.
      METHODS: Recently, our lab devised the Infant Developmental Skills Survey, a 25
      item questionnaire designed to assess sensorimotor and gross motor development.
      The questionnaire was completed by the parents of 3- to 10-month-old patients
      with infantile esotropia prior to surgery (n = 143) and the parents of 6- to 11
      month-old patients following surgery (n = 58). A subset of parents (n = 40)
      completed the questionnaire both before and after surgery. For comparison, the
      questionnaire was completed by the parents of infants with normal ocular
      alignment (n = 194). RESULTS: Before surgery 4-, 5-, 6-, 7-, 9-, and 10-month-old
      patients showed delayed achievement of sensorimotor milestones (p < 0.01), and 5
      , 9-, and 10-month-old patients demonstrated delayed attainment of gross motor
      milestones (p < 0.05) compared with normal children. However, following surgery,
      patients demonstrated a greater rate of sensorimotor development than age-matched
      controls (p < 0.0001) and caught up with normal children on both sensorimotor and
      gross motor skills. CONCLUSIONS: Prior to surgery, patients with infantile
      esotropia were delayed in their achievement of developmental milestones. However,
      following surgery, a comparison group of patients showed rapid development and
      possessed motor skills comparable to those of normal children, suggesting that
      early surgery is beneficial to both visual and motor development.

PMID- 18083594
TI  - Atypical necrotizing scleritis after strabismus surgery.
AB  - An 88-year-old woman developed necrotizing scleritis after eye muscle surgery.
      Her initial clinical presentation suggested postoperative infection, but the
      inflammation continued to progress despite antimicrobial therapy. The scleritis
      completely resolved after initiation of systemic corticosteroids. Postoperative
      necrotizing scleritis is a rare complication that occurs at the site of previous
      ocular surgery. It occurs more frequently in women with underlying systemic
      autoimmune disease and after multiple ocular procedures. We report an unusual
      case of necrotizing scleritis with inflammation that occurred after strabismus
      surgery. A specific autoimmune disease was not identified.

PMID- 18083595
TI  - Antimetabolite and releasable suture augmented filtration surgery in refractory
      pediatric glaucomas.
AB  - PURPOSE: To evaluate childhood filtration surgery when using releasable sutures,
      antimetabolites, and bleb-needling with 5-fluorouracil (5FU). METHODS:
      Retrospective case note review of 30 patients (38 eyes) with childhood glaucoma
      presenting between 1999 and 2004 to a tertiary pediatric ophthalmology center.
      Either trabeculectomy or combined trabeculotomy-trabeculectomy using
      antimetabolites, releasable sutures, and bleb modification was performed.
      Successful outcomes for survival analysis were measured intraocular pressures <
      or =21 mmHg, with two or less topical medications. RESULTS: Patients under 1 year
      old had trabeculotomy-trabeculectomy; the remainder had trabeculectomy alone. One
      case of primary congenital glaucoma had trabeculotomy-trabeculectomy at 24
      months. Eighty-nine percent had previous failed glaucoma surgery. Twenty-five
      patients (33 eyes) had primary congenital glaucoma; 5 patients (5 eyes) had
      secondary glaucoma (aphakia or pseudophakia). Mean follow-up was 22.9 months (5.2
      68.5). Sixty-six percent of all eyes had suture-release and 68% had bleb-needling
      (mean, 1.9 times). Five eyes (13%) needed further drainage tube surgery.
      Complications were early postoperative hypotony in three cases, requiring
      anterior chamber reinflation (mean age, 7.4 months at the time of surgery), two
      cases of transient wound leak, but no bleb-related complications or
      endophthalmitis. No blebs were avascular, or thin and cystic. Cumulative success
      was 75% for primary, but only 21% for secondary glaucoma at final follow-up.
      CONCLUSIONS: Antimetabolite and releasable augmentation of filtration surgery
      appear to give favorable outcomes in the treatment of refractory primary
      pediatric glaucomas. Secondary glaucomas after cataract surgery do not show good
      long-term success. There were no major or sight-threatening complications in our
      series; no eyes developed cystic avascular blebs or bleb-related infections.

PMID- 18083596
TI  - Stem cell factor and mesenchymal and neural stem cell transplantation in a rat
      model of Huntington's disease.
AB  - Neural and mesenchymal stem cells have been proposed as alternative sources of
      cells for transplantation into the brain in neurodegenerative disorders. However,
      the endogenous factors controlling their engraftment within the injured
      parenchyma remain ill-defined. Here, we demonstrate significant engraftment of
      undifferentiated exogenous mesenchymal or neural stem cells throughout the
      lesioned area in a rat model for Huntington's disease, as late as 8 weeks post
      transplantation. We show that stem cell factor (SCF), strongly up-regulated
      within host cells in the damaged striatum, is able to activate the SCF receptor c
      kit and its signaling pathway and to promote the migration and proliferation of
      mesenchymal and neural stem cells in vitro. Furthermore, c-kit receptor blockade
      alters neural stem cell distribution within the lesioned striatum. Host SCF
      expression is observed in atypical cells expressing glial fibrillary acidic
      protein and doublecortin in the lesioned striatum and in migrating doublecortin
      positive progenitors. Taken together, these data demonstrate that SCF produced in
      situ in the lesioned striatum is an important factor in promoting the engraftment
      of stem cells within the lesioned brain.

PMID- 18083597
TI  - C22H46: the smallest open 3(1)-knotted alkane by computer-aided design.
AB  - The program MolKnot [Chem. Phys. Lett. 433 (2007) 422-426] has been used in order
      to detect the smallest ever-reported alkane configured to an open-knotted shape
      with three crossings (3(1)). High level ab initio calculations support our
      findings that 22 carbon atoms are enough to create a knotted polyethylene strand
      with open ends. These tight open molecular knots exhibit unusually distorted
      geometric characteristics as multiple extended CC bonds (maximum bond length
      approximately 1.70A) and several large CCC bond angles (maximum bond angle
      approximately 145 degrees ). The energy decomposition shows that the strain
      mainly affects the valence angles of the entangled structure. We observed that
      this 22-knotted carbon atoms' region remained almost intact as a part of alkanes
      with longer chain lengths.

PMID- 18083598
TI  - Characterization and expression of the transcription factor PU.1 during LPS
      induced inflammation in the rainbow trout (Oncorhynchus mykiss).
AB  - The transcription factor PU.1 plays a key role in hematopoietic lineage
      development and therefore in determining immune cell fate. A full length cDNA
      transcript of 1237 nucleotides encoding a highly conserved putative protein of
      293 amino acids was identified by EST analysis in lipopolysaccharide (LPS)
      activated trout macrophages. Phylogenetic analyses highlight the significant
      level of structural conservation of the PU.1 transcription factor reinforcing the
      importance of this molecule in animal immunity. In trout, the PU.1 mRNA shows a
      tissue-specific expression pattern and is induced in vivo by LPS in muscle,
      liver, intestine and brain. Furthermore PU.1 is highly expressed in trout
      macrophages in primary culture. In situ expression analysis in the head kidney
      describes a large number of PU.1+ve cells distributed through the tissue in both
      LPS-treated and control animals. Cellular proliferation examined by BrdU
      immunohistochemistry (IHC) shows that LPS regulates hematopoietic processes in
      adult fish by stimulating cellular proliferation 3 days after treatment. These
      studies provide initial insights into hematopoietic/cellular processes in the
      head kidney of rainbow trout after in vivo LPS challenge.

PMID- 18083600
TI  - Fluid and particle retention in the digestive tract of the addax antelope (Addax
      nasomaculatus)--adaptations of a grazing desert ruminant.
AB  - Retention time of food in the digestive tract is a major aspect describing the
      digestive physiology of herbivores. Differences in feed retention times have been
      described for different ruminant feeding types. In this study, a dominantly
      grazing desert ruminant, the addax (Addax nasomaculatus), was investigated in
      this respect. Eight animals with a body weight (BW) of 87+/-5.3 kg on an ad
      libitum grass hay (Chloris gayana) diet were available. Co-EDTA and Cr-mordanted
      fibers (<2 mm) were used as pulse-dose markers. Mean retention time (MRT) in the
      digestive tract was calculated from faecal marker excretion. Average daily intake
      of the addax was found to be 1.7 kg dry matter (DM) or 60+/-8.3 g DM/kg BW(0.75).
      The MRT of fluid and particles in the reticulo-rumen (MRT(fluid)RR and
      MRT(particle)RR) were quantified to be 20+/-5.8 and 42+/-7.0 h respectively. When
      compared to literature data, MRT(fluid)RR was significantly longer than in cattle
      species, and MRT(particle)RR was significantly longer than in 11 taxa of all
      feeding types. The ratio of MRT(particle)RR/MRT(fluid)RR (2.3+/-0.5) was found to
      be within the range described for grazing ruminants. The long retention times
      found in the addax can be interpreted as an adaptation to a diet including a high
      proportion of slow fermenting grasses, while the long retention time of the fluid
      phase can be interpreted as a consequence of water saving mechanisms of the
      desert-adapted addax with a potentially low water turnover and capacious water
      storing rumen.

PMID- 18083601
TI  - Tonic and phasic electroencephalographic dynamics during continuous compensatory
      tracking.
AB  - Tonic and phasic dynamics of electroencephalographic (EEG) activities during a
      continuous compensatory tracking task (CTT) were analyzed using time-frequency
      analysis of EEG sources identified by independent component analysis (ICA). In 1
      hour sessions, 70-channel EEG data were recorded while participants attempted to
      use frequent compensatory trackball movements to maintain a drifting disc close
      to a bulls-eye at screen center. Disc trajectories were converted into two moving
      average performance measures, root mean square distance of the disc from screen
      center in 4-s ('local') and in 20-s ('global') moving time windows. Maximally
      independent EEG processes and their equivalent dipole source locations were
      obtained using the EEGLAB toolbox (http://sccn.ucsd.edu/eeglab). Across subjects
      and sessions, independent EEG processes in occipital, somatomotor, and
      supplementary motor cortices exhibited tonic power increases during periods of
      high tracking error, plus additional phasic power increases in several frequency
      bands before and after trackball movements following disc 'perigees' (moments at
      which the disc began to drift away from the bulls-eye). These phasic activity
      increases, which were larger during high-error periods, reveal an intimate
      relation between EEG dynamics and top-down recognition of responding to
      threatening events. Thus during a continuous tracking task without impulsive
      stimulus onsets, sub-second scale EEG dynamics related to visuomotor task could
      be dissociated from slower spectral modulations linked to changes in performance
      and arousal. We tentatively interpret the observed EEG signal increases as
      indexing tonic and phasic modulations of the levels of task attention and
      engagement required to maintain visuomotor performance during sustained
      performance.

PMID- 18083602
TI  - Somato-motor inhibitory processing in humans: an event-related functional MRI
      study.
AB  - Inhibiting inappropriate behavior and thoughts is an essential ability for
      humans, but the regions responsible for inhibitory processing are a matter of
      continuous debate. This is the first study of somatosensory go/nogo tasks using
      event-related functional magnetic resonance imaging (fMRI). Fifteen subjects
      preformed two different types of go/nogo task, i.e. (1) Movement and (2) Count,
      to compare with previous studies using visual go/nogo tasks, and confirm whether
      the inhibitory processing is dependent on sensory modalities. Go and nogo stimuli
      were presented with an even probability. Our data indicated that the response
      inhibition network involved the dorsolateral (DLPFC) and ventrolateral (VLPFC)
      prefrontal cortices, pre-supplementary motor area (pre-SMA), anterior cingulate
      cortex (ACC), inferior parietal lobule (IPL), insula, and temporoparietal
      junction (TPJ), which were consistent with previous results obtained using visual
      go/nogo tasks. These activities existed in both Movement and Count Nogo trials.
      Therefore, our results suggest that the network for inhibitory processing is not
      dependent on sensory modalities but reflects common neural activities. In
      addition, there were differences of activation intensity between Movement and
      Count Nogo trials in the prefrontal cortex, temporal lobe, and ACC. Thus,
      inhibitory processing would involve two neural networks, common and uncommon
      regions, depending on the required response mode.

PMID- 18083603
TI  - Sacral stress fracture as a cause of gluteal artery injury: an unusual
      complication of a common fracture.

PMID- 18083604
TI  - Life 12 years after temporal lobe epilepsy surgery: a long-term, prospective
      clinical study.
AB  - It has been suggested that aim of the temporal lobe epilepsy surgery is twofold:
      first is to decrease seizure frequency and second is to improve quality of life
      without causing intolerable complications. The aim of this prospective,
      longitudinal clinical study is to report outcomes with respect to seizure,
      medication, employment and quality of life in short- and long-term follow-ups
      after resective temporal lobe epilepsy surgery. Consecutively 63 patients who
      underwent resective temporal lobe epilepsy surgery between 1993 and 1994 were
      enrolled. Outcomes at 6 months, 2 and 12 years were evaluated and compared with
      pre-operative status. The mean follow-up of this study was 12.3+/-0.6 years.
      Results showed that rates of seizure freedom were 82.5, 76.2, and 70.8% at 6
      months, 2 and 12 years, respectively. Significant reduction in antiepileptic drug
      dose at long-term follow-up was found when compared to baseline. Patients after
      surgery had net gain of employment and improved quality of life was seen in all
      seizure outcome groups after surgery. Seizure-free patients showed better quality
      of life than those who continued to have seizure. Our results suggest that
      surgery leads to improvement in both seizure outcome and quality of life. Even
      years after the surgery, patients are still working, have reduced their
      medication load and have nearly normal life.

PMID- 18083605
TI  - Apomorphine for the acute treatment of "off" episodes in Parkinson's disease.
AB  - Many patients with advanced Parkinson's disease (PD) experience motor
      complications, which negatively impact quality of life, despite optimized oral
      therapy. It is important for patients to have a treatment option that may provide
      rapid relief from "off" episodes. In three pivotal, randomized, placebo
      controlled trials, subcutaneous apomorphine was effective in acutely treating
      "off" episodes, significantly improving Unified Parkinson Disease Rating Scale
      motor scores and reducing the number of "off" hours per day, with a significantly
      shorter time to patient-declared onset of relief than placebo. Thus, clinical
      trial data support the efficacy of intermittent subcutaneous apomorphine as a
      rapid acute treatment for "off" episodes in advanced PD.

PMID- 18083606
TI  - Effects of phenolic monomers on the enzymes activities and volatile fatty acids
      production of Neocallimastix frontalis B9.
AB  - The effects of phenolic monomers (i.e. rho-coumaric acid, ferulic acid, rho
      hydroxybenzaldehyde and vanillin) on the enzymes and fermentation activities of
      Neocallimastix frontalis B9 grown in ball-milled filter paper and guinea grass
      media were studied. The enzymes studied were carboxymethylcellulase (CMCase),
      filterpaperase (FPase), xylanase and beta-glucosidase. At 96 h of incubation, N.
      frontalis grown in ball-milled filter paper medium produced comparable xylanase
      and CMCase activities (0.41, 0.5 micromol/min/mg protein) while in guinea grass
      medium, N. frontalis produced higher xylanase activity than that of CMCase
      activity (2.35, 0.05 micromol/min/mg protein). The other enzymes activities were
      low. When N. frontalis was grown in ball-milled filter paper medium, only acetic
      acid was produced. However, when grown in guinea grass medium, the major end
      product was acetate, but propionic, butyric and isovaleric were also produced in
      lesser amount. Vanillin showed the least inhibitory effects to enzyme activities
      of N. frontalis B9 grown in both ball-milled filter paper and guinea grass media.
      For total volatile fatty acid production, all phenolic monomers showed inhibitory
      effects, but rho-coumaric and ferulic acids were the stronger inhibitors than rho
      hydroxybenzaldehyde and vanillin.

PMID- 18083607
TI  - Evaluation of aneugenic effects of bisphenol A in somatic and germ cells of the
      mouse.
AB  - Bisphenol A (BPA) is a synthetic monomer widely used to polymerize polycarbonate
      plastics and resins. It is shown in vitro to interfere with microtubules,
      producing aberations in mitotic and meiotic spindles. An increase of meiotic
      abnormalities in untreated female mice from an experimental colony was temporally
      correlated with the accidental release of BPA from polycarbonate cages and
      bottles damaged by inadvertent treatment with harsh alkaline detergents [P.A.
      Hunt, K.E. Koehler, M. Susiarjo, C.A. Hodges, A. Ilagan, R.C. Voigt, S. Thomas,
      B.F. Thomas, T.J. Hassold, Bisphenol A exposure causes meiotic aneuploidy in the
      female mouse, Curr. Biol. 13 (2003) 546-553]. In the present study, potential
      aneugenic effects of BPA on mouse male and female germ cells and bone marrow
      cells have been evaluated after acute, sub-chronic or chronic in vivo exposure.
      Female mice were orally treated with a single BPA dose, with 7 daily
      administrations or exposed for 7 weeks to BPA in drinking water. No significant
      induction of hyperploidy or polyploidy was observed in oocytes and zygotes at any
      treatment condition. The only detectable effect was a significant increase of
      metaphase II oocytes with prematurely separated chromatids after chronic
      exposure; this effect, however, had no irreversible consequence upon the fidelity
      of chromosome segregation during the second meiotic division, as demonstrated by
      the normal chromosome constitution of zygotes under the same exposure condition.
      With male mice, no delay of meiotic divisions was found after six daily oral
      doses of BPA with the BrdU assay. Similarly, no induction of hyperploidy and
      polyploidy was shown in epydidimal sperm hybrized with probes for chromosomes 8,
      X and Y, 22 days after six daily oral BPA doses. Finally, two daily oral BPA
      doses did not induce any increase of micronucleus frequencies in polychromatic
      erythrocytes of mouse bone marrow. In conclusion, our results do not add evidence
      to the suspected aneugenic activity of BPA and suggest that other factors or co
      factors should be considered to explain the unexpected burst of meiotic
      abnormalities previously attributed to accidental BPA exposure.

PMID- 18083608
TI  - Localised pyogranulomatous dermatitis due to Mycobacterium abscessus in a cat: a
      case report.
AB  - A case of pyogranulomatous dermatitis, caused by Mycobacterium abscessus, an
      unusual opportunistic Mycobacterium spp., is described in a cat.
      Histopathological examination of the affected skin confirmed the diagnosis and
      Ziehl-Neelsen staining revealed acid-fast rods. A rapidly growing mycobacterium
      was found after culture on a Lowenstein-Jensen medium. Real-time polymerase chain
      reaction for the 16S rDNA (434bp) sequence and the sequence of the rpoB gene
      (359bp) revealed 99% and 100% matches, respectively, with M. abscessus. This is
      the first report of a feline infection caused by this organism in Europe.

PMID- 18083609
TI  - Mechanism of oxidative DNA damage repair and relevance to human pathology.
AB  - Since DNA is prone to oxidative attack cells have evolved multiple protective
      strategies to prevent the deleterious effects of DNA oxidation. Base excision
      repair is the major mechanism for repair of DNA base damage by reactive oxygen
      species but recent evidence indicate that nucleotide excision repair proteins,
      that are mutated in human syndromes, are involved too. The mechanisms of repair
      dealing with the direct oxidation of DNA will be reviewed taking as prototype the
      oxidized base 7,8-dihydro-8-hydroxyguanine. The function of the individual repair
      components as inferred from model mice indicate that the ablation of two gene
      functions is mostly required to lead to accumulation of oxidative DNA damage,
      mutagenesis and cancer development. The recent identification of human diseases
      associated with mutations in oxidative damage repair show that defects in this
      pathway may lead to increased cancer but their major causative role seems to be
      in neurological diseases.

PMID- 18083599
TI  - Immune-related gene expression profiling of yellowtail (Seriola quinqueradiata)
      kidney cells stimulated with ConA and LPS using microarray analysis.
AB  - To better understand the immune system of a commercially important fish
      (yellowtail, Seriola quinqueradiata), we constructed a cDNA microarray containing
      1001 selected genes from yellowtail EST and used this to investigate gene
      expression of primary cultured kidney cells stimulated with ConA and LPS. The
      total number of up-regulated genes stimulated by LPS was apparently greater than
      that of ConA stimulation, whereas down-regulated genes were markedly found in
      ConA-stimulated group. Of the genes that were up-regulated at 3, 6, and 12h after
      LPS treatment, 12%, 13% and 12%, respectively, were immune-related. Immune
      related genes were sorted into 4 groups based on their differential expression
      patterns against LPS induction. LPS induced the expression of genes related to
      inflammation, cytokine activity, antigen presentation and antigen binding such
      as, IL-1beta, CC chemokine with stalk CK2, MHC class II beta chain and
      immunoglobulin heavy chain. Amplified fragments of RT-PCR products of IgM, IL
      1beta, nephrosin, and beta-actin had signal intensities that were comparable to
      those obtained with the microarray. Overall, these results show that microarrays
      are a promising tool for uncovering immune mechanism in teleost fish. cDNA
      sequences of genes were deposited in the GenBank database at DDBJ with accession
      numbers BB 996897-BB 997897.

PMID- 18083610
TI  - Hepatocellular adenoma and metabolic balance in patients with type Ia glycogen
      storage disease.
AB  - Glycogen storage disease type I (GSD I) is a metabolic disorder resulting from
      defects in the glucose-6-phosphatase system. Approximately 75% of adolescent and
      adult patients develop hepatocellular adenomas, which can lead to considerable
      morbidity and mortality. The pathogenesis of adenomas is unclear and the risk of
      developing adenomas in treated patients is uncertain. The objective of this study
      was to determine whether metabolic imbalance was related to the occurrence of
      adenomas in patients with GSD I, and to determine what specific biochemical
      pathways were involved. We performed a 1:1 case-control retrospective study;
      cases were GSD I patients with adenomas and controls were GSD I patients without
      adenomas. Controls and cases were matched according to age at diagnosis, age at
      adenoma detection, and gender. We investigated biochemical abnormalities
      indicative of metabolic balance and exogenous factors potentially related to the
      onset of adenomas in the two groups. We detected no significant differences in
      dietetic treatment, compliance to treatment, or biochemical parameters related to
      metabolic balance between the two groups. In conclusion, we were unable to
      identify any significant differences in metabolic balance between GSD I patients
      who developed adenomas and those who did not.

PMID- 18083611
TI  - Optical properties of a tetradentate bis(beta-diketonate) europium(III) complex.
AB  - Eu2(BPOPB)3H2O, an europium complex chelated with bis(beta-diketone), was
      synthesized. Its properties have been investigated by absorption spectrum,
      emission spectrum and luminescence lifetime measurement. The complex displays
      strong red luminescence upon irradiation at the ligand band around 355 nm, which
      indicates that the bis-beta-diketonate ligand BPOPB is an efficient sensitizer.
      The Judd-Ofelt parameters obtained from the emission spectrum of Eu2(BPOPB)3H2O
      have been used to calculate the total spontaneous emission probabilities (A), the
      radiative lifetime (tau(rad)), the fluorescence branching ratio (beta) and the
      stimulated emission cross-sections (sigma). The luminescence lifetimes are
      determined to be 402 and 169 micros for Eu2(BPOPB)3H2O and Eu(DBM)3(H2O)2,
      respectively. The relationship between the structures of rare-earth complexes and
      luminescence lifetimes was analyzed. The radiative properties reveal that
      Eu2(BPOPB)3H2O is potential to be an efficient luminescent material.

PMID- 18083612
TI  - Simultaneous determination of vitamin B12 and its derivatives using some of
      multivariate calibration 1 (MVC1) techniques.
AB  - Resolution of binary mixtures of vitamin B12, methylcobalamin and B12 coenzyme
      with minimum sample pre-treatment and without analyte separation has been
      successfully achieved by methods of partial least squares algorithm with one
      dependent variable (PLS1), orthogonal signal correction/partial least squares
      (OSC/PLS), principal component regression (PCR) and hybrid linear analysis (HLA).
      Data of analysis were obtained from UV-vis spectra. The UV-vis spectra of the
      vitamin B12, methylcobalamin and B12 coenzyme were recorded in the same spectral
      conditions. The method of central composite design was used in the ranges of 10
      80 mg L(-1) for vitamin B12 and methylcobalamin and 20-130 mg L(-1) for B12
      coenzyme. The models refinement procedure and validation were performed by cross
      validation. The minimum root mean square error of prediction (RMSEP) was 2.26 mg
      L(-1) for vitamin B12 with PLS1, 1.33 mg L(-1) for methylcobalamin with OSC/PLS
      and 3.24 mg L(-1) for B12 coenzyme with HLA techniques. Figures of merit such as
      selectivity, sensitivity, analytical sensitivity and LOD were determined for
      three compounds. The procedure was successfully applied to simultaneous
      determination of three compounds in synthetic mixtures and in a pharmaceutical
      formulation.

PMID- 18083613
TI  - Spectrophotometric determination of inorganic mercury (II) after preconcentration
      of its diphenylthiocarbazone complex on a cellulose column.
AB  - A simple and a relatively green methodology have been developed for the
      preconcentration of mercury based on the adsorption of its diphenylthiocarbazone
      complex on a cellulose column. The effects of various parameters such as effect
      of acidity, eluting agents, stability of the column, sample volume, interfering
      ions, etc. have been studied in detail. The adsorbed complex could be easily
      desorbed using environmentally benign polyethylene glycol-400 and the
      concentration of mercury was determined using visible spectrophotometry. The
      calibration graph was linear in the range 0-2 microg mL(-1) of mercury with a
      detection limit of 2 microg L(-1) and the validity of the proposed method was
      checked by studying the recovery of mercury in spiked tap water, well water and
      sea water samples. The highest preconcentration factor achieved for quantitative
      recovery (>95%) of mercury (II) was 33 for a 500mL sample volume. The method was
      also applied to the analysis of mercury content in city waste incineration ash
      (CRM176). The relative standard deviation of the method was found to be 3.5%.

PMID- 18083614
TI  - Dynamic stereochemistry of erigeroside by measurement of 1H-1H and 13C-1H
      coupling constants.
AB  - Erigeroside was extracted from Satureja khuzistanica Jamzad (Marzeh Khuzistani in
      Persian, family of lamiaceae), and (1)H, (13)C, (13)C{(1)H}, (1)H-(1)H COSY, HMQC
      and J-HMBC were obtained to identify this compound and determine a complete set
      of J-coupling constants ((1)J(C-H), (2)J(C-H), (3)J(C-H) and (3)J(H-H)) values
      within the exocyclic hydroxymethyl group (CH(2)OH) and anomeric center. In
      parallel, density functional theory (DFT) using B3LYP functional and split
      valance 6-311++G** basis set has been used to optimized the structures and
      conformers of erigeroside. In all calculations solvent effects were considered
      using a polarized continuum (overlapping spheres) model (PCM). The dependencies
      of (1)J, (2)J and (3)J involving (1)H and (13)C on the C(5')-C(6') (omega), C(6')
      O(6') (theta) and C(1')-O(1') (phi) torsion angles in erigeroside were computed
      using DFT method. Complete hyper surfaces for (1)J(C1',H1'), (2)J(C5',H6'R),
      (2)J(C5',H6'S), (2)J(C6',H5'), (3)J(C4',H6'R), (3)J(C4',H6'S) and (2)J(H6'R-H5'S)
      as well as (3)J(H5',H6'R) were obtained and used to derive Karplus equations to
      correlate these couplings to omega, theta and phi. These calculated J-couplings
      are in agreement with experimental values. These results confirm the reliability
      of DFT calculated coupling constants in aqueous solution.

PMID- 18083615
TI  - Acute acalculous cholecystitis during the course of primary Epstein-Barr virus
      infection: a new case and a review of the literature.
AB  - OBJECTIVE: The aim of this study was to describe a case of acute acalculous
      cholecystitis occurring in the course of primary Epstein-Barr virus (EBV)
      infection. METHODS: The clinical features of the case were analyzed and compared
      to those of three other similar cases reported in the international literature.
      RESULTS: All cases occurred in European females with cholestatic hepatitis,
      presented with gallbladder wall thickening, and recovered uneventfully without
      the need for surgical intervention. CONCLUSIONS: Acute acalculous cholecystitis
      may occur during the course of acute EBV infection, especially in patients with
      cholestatic hepatitis. Clinicians should be aware of the possible involvement of
      the gallbladder during EBV infection to avoid unnecessary invasive procedures or
      the overuse of antibiotics.

PMID- 18083616
TI  - Presence of the newly discovered human polyomaviruses KI and WU in Australian
      patients with acute respiratory tract infection.
AB  - BACKGROUND: Currently, the role of the novel human polyomaviruses, KI (KIV) and
      WU (WUV) as agents of human disease remains uncertain. OBJECTIVES: We sought to
      determine the prevalence of these viruses and their rate of co-detection with
      other viral respiratory pathogens, in an Australian population. STUDY DESIGN:
      Polymerase chain reaction assays previously described were used to examine the
      presence of KIV and WUV in 2866 respiratory specimens collected from January to
      December 2003 from Australian patients with acute respiratory infections.
      RESULTS: KIV and WUV were present in our population with an annual prevalence of
      2.6% and 4.5%, respectively. There was no apparent seasonal variation for KIV,
      but a predominance of infection was detected during late winter to early summer
      for WUV. The level of co-infection of KIV or WUV with other respiratory viruses
      was 74.7% and 79.7%, respectively. Both viruses were absent from urine and blood
      specimens collected from a variety of patient sources. CONCLUSIONS: KIV and WUV
      circulate annually in the Australian population. Although there is a strong
      association with the respiratory tract, more comprehensive studies are required
      to prove these viruses are agents causing respiratory disease.

PMID- 18083617
TI  - Comment on Destombes et al. original article "Investigations for bone metastasis
      from an unknown primary".

PMID- 18083618
TI  - Polysomnographic and quantitative EEG analysis of subjects with long-term
      insomnia complaints associated with mild traumatic brain injury.
AB  - OBJECTIVE: The aims of this study were (1) to characterise the extent and nature
      of disrupted sleep in individuals with long-term sleep complaints subsequent to
      mild traumatic brain injury (MTBI), and (2) to determine whether sleep
      disturbances in MTBI subjects were more characteristic of psychophysiological,
      psychiatric, or idiopathic insomnia. METHODS: Nine MTBI patients (27.8 months
      post-injury; SD=15.5 months) and nine control subjects underwent polysomnographic
      testing and completed self-report questionnaires on sleep quality. Power spectral
      (FFT) analysis of the sleep onset period was conducted, with both the power and
      variability in power being quantified. RESULTS: Individuals with MTBI exhibited
      long-term sleep difficulties, along with various cognitive and affective
      abnormalities. The MTBI group had 4% less efficient sleep (p=0.019), shorter REM
      onset latencies (p=0.011), and longer sleep onset latencies, although the latter
      were highly variable in the MTBI group (F-test: p=0.012). FFT analysis revealed
      greater intra-subject variability in the MTBI group in sigma, theta, and delta
      power during the sleep onset period. CONCLUSIONS: MTBI patients with persistent
      sleep complaints differ significantly from controls on a number of
      electrophysiological outcomes, but could not be easily classified into existing
      insomnia subtypes. SIGNIFICANCE: Sleep disturbances can persist well after the
      injury in a subset of patients with MTBI.

PMID- 18083619
TI  - Age-related differences in auditory evoked responses during rapid perceptual
      learning.
AB  - OBJECTIVE: Young and older adults can learn to rapidly discriminate between
      elementary visual and auditory features. While growing evidence supports the
      notion that such behavioral improvement is paralleled by neuroplastic changes in
      corresponding sensory areas during adulthood, studies have not examined practice
      related improvement in older adults and the corresponding changes in neural
      activity. METHODS: We used event-related potentials (ERPs) to investigate the
      effects of age on rapid learning-related changes in listeners' ability to
      identify two phonetically different vowels presented simultaneously. RESULTS:
      During the first hour of testing, young and older listeners showed comparable
      behavioral improvement in identifying both vowels. In young adults, learning was
      paralleled by enhanced amplitudes of early (130 ms) and late (320 ms) ERP waves
      over the right temporal lobe, as well as an increased negative wave over the
      midline parietal region, peaking at about 400 ms after sound onset. The practice
      related changes over the right temporal lobe were not present in older adults
      whereas the learning effect observed over the parietal region was present in both
      young and older adults. In older adults, behavioral improvement was also
      associated with reduced N1 amplitude recorded at inferior and posterior
      temporal/occipital scalp sites while no such changes were observed in young
      adults. CONCLUSIONS: Age-related differences in neural activity during learning
      suggest that neural networks supporting behavioral improvements in speech
      segregation and identification change during the course of aging. SIGNIFICANCE:
      This research highlights the role of practice on concurrent sound perception and
      may facilitate the development of training programs that may help older listeners
      to parse the auditory scene into component sound sources.

PMID- 18083620
TI  - Oscillatory changes related to the forced termination of a movement.
AB  - OBJECTIVE: Stimulus-induced movements are accompanied by a definite pattern of
      oscillatory changes, that include a frontal 15 Hz synchronization, a central peri
      movement desynchronization, and a contralateral beta rebound after the movement.
      Our aim was to study the oscillatory changes related to the forced termination of
      a single complex motor program (signature) and compare them with those observed
      after the normal termination of the movement. METHODS: Fifty-eight reference-free
      EEG channels were analyzed in 10 healthy subjects. A 2000 Hz tone (S1, go signal)
      indicated the subject to begin to write his/her complete signature. A second 2000
      Hz tone 0.8 s afterwards (50% probability: S2, stop signal) indicated the subject
      to stop immediately. Movement-related energy changes were evaluated by means of
      time-frequency (Gabor) transforms. RESULTS: A frontal 15 Hz synchronization was
      observed after S1, but not after S2. The amplitude of the post-movement beta
      increase was significantly lower when the movement was abnormally terminated
      (p=0.005), while the peri-movement decrease was similar. CONCLUSIONS: The forced
      termination of a motor program reduces significantly the amplitude of the post
      movement beta increment, conserving its temporal pattern. Also, the presence of
      the 15 Hz frontal synchronization only after S1, together with the results of
      previous studies, suggests that the frontal mechanisms involved in go/no go and
      stop signals are very different. SIGNIFICANCE: Our results indicate that the beta
      rebound is an active process, independent of the peri-movement beta decrease,
      which is influenced by how the movement is terminated.

PMID- 18083621
TI  - Mingling, observing, and lingering: everyday public spaces and their implications
      for well-being and social relations.
AB  - The rejuvenation of public spaces is a key policy concern in the UK. Drawing on a
      wide literature and on qualitative research located in a multi-ethnic area of
      East London, this paper explores their relationship to well-being and social
      relations. It demonstrates that ordinary spaces are a significant resource for
      both individuals and communities. The beneficial properties of public spaces are
      not reducible to natural or aesthetic criteria, however. Social interaction in
      spaces can provide relief from daily routines, sustenance for people's sense of
      community, opportunities for sustaining bonding ties or making bridges, and can
      influence tolerance and raise people's spirits. They also possess subjective
      meanings that accumulate over time and can contribute to meeting diverse needs.
      Different users of public spaces attain a sense of well- being for different
      reasons: the paper calls for policy approaches in which the social and
      therapeutic properties of a range of everyday spaces are more widely recognised
      and nurtured.

PMID- 18083622
TI  - Metalloproteinases and their inhibitors: regulators of wound healing.
AB  - Wound healing is a dynamic process that involves a coordinated response of many
      cell types representing distinct tissue compartments and is fundamentally similar
      among tissue types. Among the many gene products that are essential for
      restoration of normal tissue architecture, several members of the matrix
      metalloproteinase (MMP) family function as positive and, at times, negative
      regulators of repair processes. MMPs were initially thought to only function in
      the resolution phase of wound healing, particularly during scar resorption;
      however, recent evidence suggests that they also influence other wound-healing
      responses, such as inflammation and re-epithelialization. In this review, we
      discuss what is currently known about the function of MMPs in wound healing and
      will provide suggestions for future research directions.

PMID- 18083623
TI  - The SarA protein family of Staphylococcus aureus.
AB  - Staphylococcus aureus is widely appreciated as an opportunistic pathogen,
      primarily in hospital-related infections. However, recent reports indicate that
      S. aureus infections can now occur in other wise healthy individuals in the
      community setting. The success of this organism can be attributed to the large
      array of regulatory proteins, including the SarA protein family, used to respond
      to changing microenvironments. Sequence alignment and structural data reveal that
      the SarA protein family can be divided into three subfamilies: (1) single domain
      proteins; (2) double domain proteins; (3) MarR homologs. Structural studies have
      also demonstrated that SarA, SarR, SarS, MgrA and thus possibly all members of
      this protein family are winged helix proteins with minor variations. Mutagenesis
      studies of SarA disclose that the winged helix motifs are important for DNA
      binding and function. Recent progress concerning the functions and plausible
      mechanisms of regulation of SarA and its homologs are discussed.

PMID- 18083624
TI  - Transforming growth factor-beta-induced gene product, as a novel ligand of
      integrin alphaMbeta2, promotes monocytes adhesion, migration and chemotaxis.
AB  - Monocyte recruitment from the blood in response to chemoattractant gradients is a
      key phenomenon in inflammation. Various extracellular matrix proteins, at the
      site of inflammation, have chemoattractant activity and mediate monocyte adhesion
      and migration as ligands of integrins. In this report, we demonstrate that
      transforming growth factor-beta-induced gene product (betaig-h3/TGFBIp), as an
      extracellular matrix protein, mediates monocytes adhesion under both static and
      flow conditions mainly through integrin alphaMbeta2. Fasciclin 1 domains of
      betaig-h3/TGFBIp are responsible for the interaction with integrin alphaMbeta2,
      not only enhances monocyte migration in both chemotactic and haptotactic manners
      but also mediates their transendothelial migration and subendothelial matrix
      invasion. These activities are also mediated through integrin alphaMbeta2.
      Intraperitoneal injection of betaig-h3/TGFBIp promotes the recruitment of
      monocytes but not neutrophils. Our results demonstrate that betaig-h3/TGFBIp
      produced at inflammatory sites is a novel chemoattractant for monocytes and
      interacts with integrin alphaMbeta2 to serve as a substrate for their migration,
      suggesting that betaig-h3/TGFBIp plays an important role in inflammation.

PMID- 18083625
TI  - A fitting tale.

PMID- 18083626
TI  - Mechanistic investigations of low dose exposures to the genotoxic compounds
      bisphenol-A and rotenone.
AB  - A complete hazard and risk assessment of any known genotoxin requires the
      evaluation of the mutagenic, clastogenic and aneugenic potential of the compound.
      In the case of aneugenic chemicals, mechanism of action (MOA) and quantitative
      responses may be investigated by studying their effects upon the fidelity of
      functioning of components of the cell cycle. These present studies have
      demonstrated that the plastics component bisphenol-A (BPA) and the natural
      pesticide rotenone induce micronuclei and modify the functioning of the
      microtubule organising centres (MTOCs) of the mitotic spindles of cultured
      mammalian cells in a dose-dependent manner. BPA and rotenone were used as model
      compounds in an investigation of dose response relationships for the hazard/risk
      assessment of aneugens. Thresholds of action for the induction of aneuploidy have
      been predicted for spindle poisons on the basis of the multiple targets, which
      may need disabling before a quantitative response can be detected. The
      cytokinesis blocked micronucleus assay (CBMA) methodology was utilised in the
      human lymphoblastoid cell lines AHH-1, MCL-5 and Chinese hamster V79 cell lines.
      A no observable effect level (NOEL) at 10.8 microg/ml BPA was observed for MN
      induction. Rotenone showed a small increase in MN induction with the first
      significant effect at 0.25 ng/ml in V79 cells but there was no significant effect
      in the metabolically competent cell line, MCL-5. For a mechanistic evaluation of
      the aneugenic effects of BPA and rotenone, fluorescently labelled antibodies were
      used to visualise microtubules (alpha-tubulin) and MTOCs (gamma-tubulin). The
      NOELs for tripolar mitotic spindle induction in V79 cells were 7 microg/ml for
      BPA and 80 pg/ml for rotenone (concentrations which produced similar changes to
      mitotic index (M.I.)). Interestingly there was close proximity to the NOEL of
      10.8 microg/ml BPA for micronucleus (MN) induction in the human lymphoblastoid
      AHH-1 cell. Multiple MTOCs can therefore be predicted as a possible mechanism for
      MN induction. The similarity in concentration inducing tripolar mitosis, M.I. and
      MN changes suggests immunofluorescence analysis to be a useful dose setting assay
      with emphasis on the mechanism.

PMID- 18083627
TI  - Rapid assays for the diagnosis of influenza A and B viruses in patients evaluated
      at a large tertiary care children's hospital during two consecutive winter
      seasons.
AB  - BACKGROUND: The rapid and accurate diagnosis of influenza facilitates antiviral
      therapy, judicious antibiotic usage, and cohorting patients to decrease
      nosocomial infection. OBJECTIVE: To determine the utility of rapid influenza
      tests in a children's hospital. STUDY DESIGN: Two in vitro rapid
      immunochromatographic assays that detect and distinguish influenza A and B
      viruses were compared to the reference standard of viral culture. RESULTS: In
      9186 patients tested, overall sensitivity of the rapid assays for influenza A was
      64.4% and specificity was 98.3%. Sensitivity and specificity were 28% and 99.9%,
      respectively, for influenza B. Overall sensitivity and specificity for Remel
      Xpect (2004/2005) were 47.7% and 98.7% for influenza A, and 20.3% and 99.8% for
      influenza B, respectively. Overall sensitivity and specificity of Binax NOW Flu
      A&B (2005/2006) were 78.3% and 98% for influenza A, and 35.9% and 99.9% for
      influenza B, respectively. The results for influenza B with both assays were
      significantly lower than previously reported and lower than stated in the
      manufacturer's package insert. CONCLUSIONS: In a contemporary clinical setting,
      rapid assays for influenza displayed significantly lower sensitivities,
      especially for influenza B, than prior reports. Differences in pre- and post
      licensure performance demonstrate the importance of continuous evaluation of
      rapid diagnostic tests for influenza.

PMID- 18083628
TI  - Acute and chronic effects of ethanol on cortical excitability.
AB  - OBJECTIVE: We designed this study to find out whether 5Hz repetitive transcranial
      magnetic stimulation (rTMS) would disclose changes in cortical plasticity after
      acute intake of ethanol and in patients with chronic alcohol consumption.
      METHODS: Ten stimuli-5Hz-rTMS trains were applied over the primary motor cortex
      in 10 healthy subjects before and after acute ethanol intake and in 13 patients
      with chronic ethanol abuse, but negative blood ethanol levels when studied. The
      motor evoked potential (MEP) amplitude and the cortical silent period (CSP)
      duration during the course of rTMS trains were measured. Short-interval
      intracortical inhibition (3ms) and intracortical facilitation (10ms) were studied
      by paired-pulse TMS in 4 healthy subjects and 4 patients. RESULTS: In healthy
      subjects before and after acute ethanol intake, 5Hz-rTMS produced a significant
      increase in the MEP size and CSP duration during rTMS. The first CSP in the train
      was significantly longer after than before ethanol intake. In patients 5Hz-rTMS
      failed to produce the normal MEP facilitation but left the CSP increase
      unchanged. CONCLUSIONS: Acute and chronic ethanol intake alters cortical
      excitability and short-term plasticity of the primary motor cortex as tested by
      the MEP size facilitation and CSP lengthening after 5Hz-rTMS. SIGNIFICANCE: This
      finding suggests that rTMS is a valid tool for investigating the effects of
      ethanol on cortical plasticity in humans.

PMID- 18083629
TI  - An investigation of the validity of the Lifeshirt in comparison to standard
      polysomnography in the detection of obstructive sleep apnea.
AB  - BACKGROUND: Due to the cost and waiting times for traditional sleep studies,
      there is great interest in finding alternatives for the diagnosis of sleep apnea.
      Several alternatives exist, including ambulatory devices. Our laboratory utilized
      one such device, a form-fitting vest called the Lifeshirt, and compared its
      accuracy to that of polysomnography (PSG). METHODS: PSG was performed with
      simultaneous utilization of the Lifeshirt on 50 individuals who met screening
      criteria for obstructive sleep apnea. Participants came to the sleep laboratory
      approximately 2 h before their normal bedtime. A sleep technician prepared each
      participant for PSG and Lifeshirt monitoring. "Lights Out" occurred when the
      participant was ready for bed, and time in bed was standardized to approximately
      7 h. PSGs were scored by experienced personnel in our laboratory, while Lifeshirt
      data were sent electronically to the Lifeshirt manufacturer for analysis. The
      major variable that was compared between PSG and Lifeshirt was the apnea hypopnea
      index (AHI), or the number of apneas and hypopneas per hour. Due to incomplete
      data on two participants, analyses were completed on 48 individuals. RESULTS:
      Sensitivity of the Lifeshirt ranged from .85 (AHI of > or =5) to 1.00 (AHI of >
      or =25). Specificity ranged from .67 to 1.00. Using the Bland-Altman technique of
      determining agreement, the mean difference between the AHI of the Lifeshirt and
      PSG was 1.02 (+/-16.36). When these values are plotted, every case falls within
      the limits of agreement, with one exception. CONCLUSIONS: The Lifeshirt compared
      favorably with PSG and could be used with considerable confidence for the
      screening of patients with suspected obstructive sleep apnea.

PMID- 18083630
TI  - The APOE epsilon4 allele increases the risk of impaired spatial working memory in
      obstructive sleep apnea.
AB  - BACKGROUND: Contradictory data have been published on the influence of
      Apolipoprotein E (APOE) epsilon4 allele on obstructive sleep apnea (OSA). The
      aims of this study were to confirm the presence of specific neuropsychological
      changes in OSA patients carrying the APOE epsilon4 allele and to clarify if these
      changes are due to the sole presence of this allele or to its interactions with
      OSA pathology. METHODS: The APOE genotype was examined in 123 patients with OSA
      and in 121 controls, together with a series of neuropsychological tests. RESULTS:
      OSA and control subjects had similar APOE genotype and allele distribution, but
      when neuropsychological tests were considered, OSA patients showed significantly
      lower values for verbal long-term (delayed free recall at the Rey auditory-verbal
      learning test) and working memory (bisyllabic words). Moreover, spatial span was
      found to be lower in OSA epsilon4 allele carriers than in non-carriers; this
      difference was not observed in controls. CONCLUSIONS: This study confirms the
      presence of a verbal memory impairment in OSA patients and provides evidence for
      a significant interaction of APOE epsilon4 allele and OSA on frontal lobe
      function in adults, possibly mediated by the presence of specific frontal lobe
      neuroanatomical changes in these patients.

PMID- 18083631
TI  - Technical performance during soccer matches of the Italian Serie A league: effect
      of fatigue and competitive level.
AB  - The purpose of this study was to examine the changes in technical and physical
      performance between the first and second half during official matches of Italian
      Serie A league. Further aim was to compare the technical and physical performance
      of the players of the more successful teams (ranked in the first 5 positions)
      with the players of the less successful teams (ranked in the last 5 positions)
      from the same league. A total of 416 individual games from 186 soccer players
      (27+/-4 years, 76+/-5kg, and 181+/-5cm) were analysed using a video match
      analysis system. The match performance parameters analysed were: total distance
      covered (TD), high-intensity running distance (HIR), very high-intensity running
      distance (VHIR), total distance with the ball (TDB), high-intensity running
      distance with the ball (HIRB), and very high-intensity running distance with the
      ball (VHIRB). The number of skill involvements was also measured. The players
      from the more successful teams covered greater TDB and HIRB and also had more
      involvements with the ball, completed more short passes, successful short passes,
      tackles, dribbling, shots and shots on target compared to the less successful
      teams (P<0.01). A significant decline (P<0.01) between the first and second half
      was found for both physical performance and some technical scores (involvements
      with the ball, short passes and successful short passes). This study showed a
      decline in technical and physical performance between the first and second half,
      and that both physical performance and technical skills were different between
      players from more successful and less successful teams.

PMID- 18083632
TI  - Social influences on physical activity in Anglo-Australian and Vietnamese
      Australian adolescent females in a single sex school.
AB  - Social support is a consistent correlate of youth physical activity (PA) but few
      studies have examined this in cultural sub-groups. Female adolescents (n=113;
      13.9+/-0.6years) from a metropolitan single sex private school participated in
      this study. PA was estimated using the 3 Day Physical Activity Recall (3dPAR),
      and aspects of social support using a specifically designed questionnaire. Anglo
      Australians (n=74), whose parents were both born in Australia, were compared with
      Vietnamese-Australians (n=39), whose parents were both born in Vietnam. There
      were non-significant trends towards higher engagement in all measures of PA among
      Anglo-Australians. Anglo-Australians perceived higher levels of social support to
      be physically active. In the whole sample and in cultural sub-groups, support by
      mothers was a consistent predictor of PA. Among Vietnamese-Australians,
      activities shared with the mother predicted moderate to vigorous PA.
      Interventions targeting PA among adolescent females should consider interactions
      of social support and cultural background.

PMID- 18083633
TI  - A single exercise test for assessing physiological and performance parameters in
      elite rowers: the 2-in-1 test.
AB  - Testing to determine blood lactate thresholds for prescription of rowing training
      is usually conducted separately from performance testing (i.e. 2000m time trial).
      The purpose of this study was to investigate whether the testing required to
      determine blood lactate thresholds and performance in elite rowers could be
      reduced by undertaking a single test combining incremental exercise with a 2000m
      time trial. Ten elite rowers (age 20.9+/-2.1 years, mean+/-S.D.) performed, on
      separate occasions and in random order, an incremental seven-step rowing test
      (INCR), a 2000m time trial (2k), or a combined test involving the performance of
      six incremental submaximal workloads followed by 15min of recovery and then a
      2000m time trial (2-in-1). Physiological and performance parameters (blood
      lactate thresholds, accumulated oxygen deficit, heart rate, work parameters)
      determined during 2-in-1 were not significantly different from those determined
      during INCR or 2k, except for peak oxygen uptake which was higher during 2-in-1
      compared with INCR (4.23+/-0.22 versus 4.14+/-0.20lmin(-1), p=0.02), and peak
      rating of perceived exertion which was lower during 2-in-1 compared with INCR
      (19.4+/-0.2 versus 19.9+/-0.1, p=0.02). We conclude that physiological and
      performance parameters that have traditionally been assessed during separate
      incremental exercise and 2000m time trial testing in elite rowers can be validly
      determined during a single combined exercise test.

PMID- 18083634
TI  - Effect of cold water immersion after exercise in the heat on muscle function,
      body temperatures, and vessel diameter.
AB  - Cold water immersion (CWI) is a popular recovery modality, but actual
      physiological responses to CWI after exercise in the heat have not been well
      documented. The purpose of this study was to examine effects of 20-min CWI (14
      degrees C) on neuromuscular function, rectal (T(re)) and skin temperature
      (T(sk)), and femoral venous diameter after exercise in the heat. Ten well-trained
      male cyclists completed two bouts of exercise consisting of 90-min cycling at a
      constant power output (216+/-12W) followed by a 16.1km time trial (TT) in the
      heat (32 degrees C). Twenty-five minutes post-TT, participants were assigned to
      either CWI or control (CON) recovery conditions in a counterbalanced order. T(re)
      and T(sk) were recorded continuously, and maximal voluntary isometric contraction
      torque of the knee extensors (MVIC), MVIC with superimposed electrical
      stimulation (SMVIC), and femoral venous diameters were measured prior to
      exercise, 0, 45, and 90min post-TT. T(re) was significantly lower in CWI
      beginning 50min post-TT compared with CON, and T(sk) was significantly lower in
      CWI beginning 25min post-TT compared with CON. Decreases in MVIC, and SMVIC
      torque after the TT were significantly greater for CWI compared with CON;
      differences persisted 90min post-TT. Femoral vein diameter was approximately 9%
      smaller for CWI compared with CON at 45min post-TT. These results suggest that
      CWI decreases T(re), but has a negative effect on neuromuscular function.

PMID- 18083635
TI  - Effect of resistance exercise training combined with relatively low vascular
      occlusion.
AB  - Previous studies have demonstrated that a low-intensity resistance exercise,
      combined with vascular occlusion, results in a marked increase in muscular size
      and strength. We investigated the optimal pressure for reduction of muscle blood
      flow with resistance exercise to increase the muscular strength and endurance.
      Twenty-one subjects were randomly divided into four groups by the different
      application of vascular occlusion pressure at the proximal of thigh: without any
      pressure (0-pressure group), with a pressure of 50mmHg (50-pressure group), with
      a pressure of 150mmHg (150-pressure group), and with a pressure of 250mmHg (250
      pressure group). The isokinetic muscle strength at angular velocities of 60 and
      180 degrees /s, total muscle work, and the cross-sectional knee extensor muscle
      area were assessed before and after exercise. Exercise was performed three times
      a week over an 8-week period at an intensity of approximately 20% of one
      repetition maximum for straight leg raising and hip joint adduction and maximum
      force for abduction training. A significant increase in strength at 180 degrees
      /s was noted after exercise in all subjects who exercised under vascular
      occlusion. Total muscle work increased significantly in the 50- and 150-pressure
      groups (P<0.05, P<0.01, respectively). There was no significant increase in cross
      sectional knee extensor muscle area in any groups. In conclusion, resistance
      exercise with relatively low vascular occlusion pressure is potentially useful to
      increase muscle strength and endurance without discomfort.

PMID- 18083636
TI  - Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast
      cancer: 100-month analysis of the ATAC trial.
AB  - BACKGROUND: Little data exist on whether efficacy benefits or side-effects
      persist after 5 years of adjuvant treatment with an aromatase inhibitor. We aimed
      to study long-term outcomes in the Arimidex, Tamoxifen, Alone or in Combination
      (ATAC) trial that compares anastrozole with tamoxifen after a median follow-up of
      100 months. METHODS: We analysed postmenopausal women with localised invasive
      breast cancer. The primary endpoint disease-free survival (DFS), and the
      secondary endpoints time to recurrence (TTR), incidence of new contralateral
      breast cancer (CLBC), time to distant recurrence (TTDR), overall survival (OS),
      and death after recurrence were assessed in the total population (intention to
      treat; ITT: anastrozole, n=3125; tamoxifen, n=3116; total 6241) and the hormone
      receptor-positive subpopulation, the clinically important subgroup for which
      endocrine treatment is now known to be effective (84% of ITT: anastrozole,
      n=2618; tamoxifen, n=2598; total 5216). After treatment completion, fractures and
      serious adverse events continued to be collected blindly (safety population:
      anastrozole, n=3092; tamoxifen, n=3094; total 6186). This study is registered as
      an International Standard Randomised Controlled Trial, number ISRCTN18233230.
      FINDINGS: At a median follow-up of 100 months (range 0-126), DFS, TTR, TTDR, and
      CLBC were improved significantly in the ITT and hormone-receptor-positive
      populations. For hormone-receptor-positive patients: DFS hazard ratio (HR) 0.85
      (95% CI 0.76-0.94), p=0.003; TTR HR 0.76 (0.67-0.87), p=0.0001; TTDR HR 0.84
      (0.72-0.97), p=0.022; and CLBC HR 0.60 (0.42-0.85), p=0.004. Absolute differences
      in time to recurrence increased over time (TTR 2.8% [anastrozole 9.7%vs tamoxifen
      12.5%] at 5 years and 4.8% [anastrozole 17.0%vs tamoxifen 21.8%] at 9 years) and
      recurrence rates remained significantly lower on anastrozole compared with
      tamoxifen after treatment completion (HR 0.75 [0.61-0.94], p=0.01). The fewer
      deaths after recurrence (anastrozole 245 vs tamoxifen 269) was not significant
      (HR 0.90 [0.75-1.07], p=0.2), and no effect was noted for OS (anastrozole 472 vs
      tamoxifen 477) HR 0.97 [0.86-1.11], p=0.7). Fracture rates were higher in
      patients receiving anastrozole than in those receiving tamoxifen during active
      treatment (number [annual rate]: 375 [2.93%] vs 234 [1.90%]; incidence rate ratio
      [IRR] 1.55 [1.31-1.83], p<0.0001), but were not different after treatment was
      completed (off treatment: 146 [1.56%] vs 143 [1.51%]; IRR 1.03 [0.81-1.31],
      p=0.79). We did not note any significant difference in risk of cardiovascular
      morbidity or mortality between anastrozole and tamoxifen treatment groups.
      INTERPRETATION: These data show long-term safety findings and establish clearly
      the long-term efficacy of anastrozole compared with tamoxifen as initial adjuvant
      treatment for postmenopausal women with hormone-sensitive, early breast cancer,
      and provide statistically significant evidence of a larger carryover effect after
      5 years of adjuvant treatment with anastrozole compared with tamoxifen.

PMID- 18083637
TI  - T cell-antigen-presenting cell interactions visualized in vivo in a model of
      antigen-specific inflammation.
AB  - Videomicroscopy is being used increasingly to characterize the interaction of T
      cells and antigen-presenting cells (APCs) within lymphatic tissues but has not
      been reported, to our knowledge, at sites of inflammation. We employed intravital
      videomicroscopy to study an anterior uveitis model using DO11.10 T cells and
      ovalbumin (OVA). T cell movement in iris was consistent with a random walk
      independent of the presence of recognized antigen and had a lateral speed slower
      than T cells in lymph node. Lingering of T cells adjacent to APCs suggested that
      they were physically interacting. This apparent contact demonstrated antigen
      specificity when comparing results from DO11.10 cells with OVA versus bovine
      serum albumin (BSA) loaded APCs but not when comparing results from OVA-loaded
      APCs with DO11.10 versus HA clonotype 6.5 T cells. Further studies with this
      model system should clarify the contribution of T cell-APC communication at a
      site of inflammation, infection, or immunization.

PMID- 18083638
TI  - Symptomatic lumbar mobile segment with spinal canal stenosis in a fused spine
      associated with diffused idiopathic skeletal hyperostosis.
AB  - BACKGROUND CONTEXT: Chronic, continuous stress at the junction of a
      stable/unstable site of the spine in diffuse idiopathic skeletal hyperostosis
      (DISH) has been reported to cause a nonunion. Back pain resulting from the
      nonunion has been rarely reported and few operative treatments have been
      suggested. PURPOSE: To report and discuss the pathogenesis, treatment, and
      surgical outcome of a rare cause of back pain. STUDY DESIGN: Case report of back
      pain caused by a single lumbar segment is lacking bony union at the caudal end of
      a fused spine associated with diffuse idiopathic skeletal hyperostosis. METHODS:
      Back pain in a 66-year-old man who had suffered for 10 years worsened. The back
      pain and thigh pain became intolerable, and the left buttock and thigh became
      numb. Radiographs and computed tomography images showed continuous hyperostosis
      in the anterior aspect of the vertebral bodies from C2 to L2. At the caudal
      adjacent level of these fused segments, L2/3 level was mobile and had canal
      stenosis. Decompression and posterior lumbar interbody fusion (PLIF) were
      performed. RESULTS: The pain disappeared soon after the operation. The nonunited
      segment showed bony union at the 5-year follow-up. CONCLUSIONS: PLIF may be an
      option for surgically treating symptomatic nonunited lumbar segments at the
      caudal end of a fused spine with DISH in cases unresponsive to conservative
      treatment.

PMID- 18083640
TI  - Effects of electroacupuncture on gastric motility and heart rate variability in
      conscious rats.
AB  - To clarify the mechanism of site-specific effects of acupuncture on gastric motor
      function, we studied the simultaneous recording of gastric motility and
      electrocardiogram (ECG) for heart rate variability (HRV) analysis in conscious
      rats. Gastric motility and ECG were recorded before, during and after
      electroacupuncture (EA) at ST-36 (hind limb) or ST-25 (abdomen). EA at ST-36
      significantly increased gastric motility and decreased the ratio of low frequency
      (LF)/high frequency (HF) of the HRV analysis. In contrast, EA at ST-25
      significantly inhibited gastric motility and increased LF/HF ratio. There was a
      significant correlation observed between the changes of gastric motility and
      LF/HF ratio in response to EA. It is suggested that the stimulatory effect of EA
      at ST-36 on gastric motility is associated with its stimulatory effect on vagal
      activity. The inhibitory effect of EA at ST-25 on gastric motility is associated
      with its stimulatory effect on the sympathetic nerve activity.

PMID- 18083641
TI  - Simultaneous determination of ginsenoside Rg1, Re, Rd, Rb1 and ophiopogonin D in
      rat plasma by liquid chromatography/electrospray ionization mass spectrometric
      method and its application to pharmacokinetic study of 'SHENMAI' injection.
AB  - A sensitive and rapid liquid chromatography-mass spectrometric method for the
      simultaneous determination of ginsenoside Rg1, Re, Rd, Rb1 and ophiopogonin D in
      rat plasma was developed and validated. Chromatographic separation was performed
      on a C18 column using a step gradient program with the mobile phase of 0.5mmol/L
      ammonium chloride solution and acetonitrile. The analytes and I.S. were detected
      using an electrospray negative ionization mass spectrometry in the selected ion
      monitoring (SIM) mode. The method was linear over the investigated concentration
      range with a good correlation coefficient higher than 0.997. The lower limits of
      detection (LLOD) of these analytes were all lower than 2.0ng/mL. The intra- and
      inter-day precisions were all no more than 7.5% and accuracies were within the
      range of 97.5-107.0%. The validated method was successfully applied to
      investigate the pharmacokinetics of ginsenoside Rg1, Re, Rd, Rb1 and ophiopogonin
      D in rat after intravenous administration of 'SHENMAI' injection.

PMID- 18083639
TI  - Putative mechanisms behind effects of spinal cord stimulation on vascular
      diseases: a review of experimental studies.
AB  - Spinal cord stimulation (SCS) is a widely used clinical technique to treat
      ischemic pain in peripheral, cardiac and cerebral vascular diseases. The use of
      this treatment advanced rapidly during the late 80's and 90's, particularly in
      Europe. Although the clinical benefits of SCS are clear and the success rate
      remains high, the mechanisms are not yet completely understood. SCS at lumbar
      spinal segments (L2-L3) produces vasodilation in the lower limbs and feet which
      is mediated by antidromic activation of sensory fibers and decreased sympathetic
      outflow. SCS at thoracic spinal segments (T1-T2) induces several benefits
      including pain relief, reduction in both frequency and severity of angina
      attacks, and reduced short-acting nitrate intake. The benefits to the heart are
      not likely due to an increase, or redistribution of local blood flow, rather,
      they are associated with SCS-induced myocardial protection and normalization of
      the intrinsic cardiac nervous system. At somewhat lower cervical levels (C3-C6),
      SCS induces increased blood flow in the upper extremities. SCS at the upper
      cervical spinal segments (C1-C2) increased cerebral blood flow, which is
      associated with a decrease in sympathetic activity, an increase in vasomotor
      center activity and a release of neurohumoral factors. This review will summarize
      the basic science studies that have contributed to our understanding about
      mechanisms through which SCS produces beneficial effects when used in the
      treatment of vascular diseases. Furthermore, this review will particularly focus
      on the antidromic mechanisms of SCS-induced vasodilation in the lower limbs and
      feet.

PMID- 18083642
TI  - Immersion behavior of gelatin-containing calcium phosphate cement.
AB  - Calcium phosphate cements (CPCs) have many favorable properties that support
      their clinical use as bone defect repair. However, it is difficult to deliver to
      the required site and hard to compact adequately due to inherently low ductility
      of ceramics. The aim of this study focused on the effect of the gelatin content
      on properties of CPCs. The diametral tensile strength, morphology, and weight
      loss of gelatin cements were evaluated after immersion in physiological solution,
      in addition to setting time. The results indicated that the setting time
      significantly increased with increasing gelatin amount. The 2 wt.% gelatin could
      make CPCs attain the maximum strength value of 2.1 MPa at 15-day immersion, while
      1.6 MPa for the cement without gelatin. It is concluded that the presence of
      gelatin improved mechanical properties of CPCs; in particular, 2 wt.% gelatin.
      CPCs containing 2 wt.% gelatin hardened in an acceptable time recommended for
      clinical applications.

PMID- 18083643
TI  - Transgender patient satisfaction following reduction mammaplasty.
AB  - AIM: To evaluate the outcome of reduction mammaplasty in female-to-male
      transgender patients. METHOD: A 5-year retrospective review was conducted on all
      female-to-male transgender patients who underwent reduction mammaplasty. A postal
      questionnaire was devised to assess patient satisfaction, surgical outcome and
      psychological morbidity. RESULTS: Seventeen patients were identified. The senior
      author performed bilateral reduction mammaplasties and free nipple grafts in 16
      patients and one patient had a Benelli technique reduction. Complications
      included two haematomas, one wound infection, one wound dehiscence and three
      patients had hypertrophic scars. Secondary surgery was performed in seven
      patients and included scar revision, nipple reduction/realignment, dog-ear
      correction and nipple tattooing. The mean follow-up period after surgery was 10
      months (range 2-23 months). Twelve postal questionnaires were completed (response
      rate 70%). All respondents expressed satisfaction with their result and no
      regret. Seven patients had nipple sensation and nine patients were satisfied with
      nipple position. All patients thought their scars were reasonable and felt that
      surgery had improved their self-confidence and social interactions. CONCLUSION:
      Reduction mammaplasty for female-to-male gender reassignment is associated with
      high patient satisfaction and a positive impact on the lives of these patients.

PMID- 18083644
TI  - Delayed, bilateral, non-microvascular ear replantation after violent amputation.
AB  - Amputation of any body part is undoubtedly a traumatic experience leaving a
      terrible deformity, especially when the part or parts involved are visible and
      constitute an essential component of someone's facial whole. Bilateral ear
      amputation and successful subsequent replantation has been reported historically,
      but not in the modern surgical literature. We report the case of a 27-year-old
      female who was abducted and suffered a bilateral ear amputation at the hands of
      one of her captors to speed delivery of ransom money; the severed parts were sent
      to the parents approximately 2 hours after the amputation had taken place, and
      the girl was released some 48 hours after the ears were delivered. Microvascular
      replantation was attempted immediately after admission to the hospital some 2
      hours after her release, but failed, and so a non-microvascular replantation was
      performed and was successful, after approximately 54 hours of ischaemia time. We
      consider this the first report of a complete bilateral, delayed, non
      microvascular, successful ear replantation in a human being in the modern
      literature.

PMID- 18083646
TI  - Hidden plastic surgery activity.

PMID- 18083645
TI  - Immunosuppression in an emerging field of plastic reconstructive surgery:
      composite tissue allotransplantation.
AB  - Composite tissue transplantation (CTA) refers to the transplantation of an
      allograft consisting of heterogeneous cadaveric tissues. It provides a means of
      restoring structural, functional and aesthetic form in severely injured patients.
      Recent progress in facial transplantation has highlighted the immense strides
      made in this field of reconstructive surgery. However the potential for
      improvements in quality of life must be offset by the need for life-long
      immunosuppression in adults with non life-threatening injuries. The benefits and
      difficulties of immunosuppressive drugs have been established in solid organ
      transplantation. Regimens derived from renal transplantation have been
      successfully applied to CTA. However the published incidence of complications
      seen in organ transplant recipients may not be easily extrapolated to potential
      CTA candidates and may be overstated. Accepted views that high dose
      immunosuppression would be needed to overcome highly antigenic tissues such as
      skin have not been borne out by clinical experience. It is therefore important to
      assess the current state of affairs, attempt to quantify the perceived risks and
      explore novel research methods being investigated. In doing so one can make a
      well-informed judgment of the potential benefit of this surgical modality as an
      integral part of the reconstructive ladder.

PMID- 18083647
TI  - The use of peritoneal tissue mobilised with a novel laparoscopic technique to
      reconstruct a neovagina.
AB  - The use of the peritoneum to construct the new lining of the vagina was described
      40 years ago. However, the technique required open laparotomy and extensive
      dissection of the peritoneum and this technical difficulty and morbidities
      associated with the procedure reduced the acceptance of this technique.
      Subsequently, outcomes achievable from any neo-vaginoplastic techniques for a
      vaginal deformity, regardless of the aetiology, have been problematic due to
      peritoneal reflection at the pelvic floor, lack of ideal tissues to line a
      neovagina, and cicatricial contracture. The advent of the endoscope renewed
      interest in using peritoneal tissues in vaginal reconstruction, and peritoneal
      tissue mobilisation using forceps to grasp the tissue from below has been
      described. Here, we use a novel device to push a segment of mobilised peritoneum
      caudally into the vault. We have used this technique successfully in 12
      individuals with congenital vaginal agenesis. Under laparoscopic guidance and
      from the pelvic cavity, a novel instrument was used to push peritoneal tissue
      down to the introitus, incised, and sutured to the margin of the skin and mucous
      membrane to form a new introitus. All the new peritoneal linings survived and the
      diameter, depth, and moisture of the neovaginas allowed for satisfactory sexual
      intercourse and did not produce unpleasant odour or excessive secretion.
      Advantages of this operative technique include its simplicity, the reduced
      possibility of severe complications in the abdominal cavity, the avoidance of
      severe morbidity in the perineal region, and the production of a functional,
      hygienic vagina. It is our preferred and recommended method to reconstruct the
      vagina.

PMID- 18083648
TI  - MDCT of small bowel tumours.
AB  - Primary benign and malignant neoplasm of the small bowel are rare. Malignant
      tumours often present late symptoms resulting in a poor prognosis. Early
      detection of small bowel neoplasms is desirable but challenging for both
      clinicians and radiologists. Conventional double contrast enteroclysis was the
      method of choice in small bowel imaging but is increasingly being replaced by
      cross-sectional imaging methods as computed tomography (CT) and magnetic
      resonance imaging (MRI). Multidetector CT (MDCT) produces high-resolution cross
      sectional imaging of the abdomen and the small bowel. It allows multiplanar
      visualisation of small bowel tumours, demonstrates signs of small bowel
      obstruction as well as the mural and extramural extent of small bowel
      malignancies. This aids planning for surgical resection. In addition, liver
      metastases or peritoneal seeding can be detected with CT. The best visualisation
      of small bowel neoplasms is achieved with CT enteroclysis or enterography and
      this review discusses these techniques and MDCT characteristics of small bowel
      tumours.

PMID- 18083649
TI  - Radionuclides in the management of thyroid cancer.
AB  - Nuclear medicine imaging was born over 60 years ago with imaging of thyroid
      conditions. Most of our present imaging devices were developed for imaging of the
      thyroid and thyroid cancer. Millions of patients in over 100 countries have been
      diagnosed and treated for thyroid cancer using nuclear medicine techniques. It
      remains, however, one of the most dynamic areas of development in nuclear
      medicine with new roles for positron emission tomography and receptor based
      imaging. In addition to this is research into combinations of genetic therapy and
      radioisotopes and receptor based therapy using beta emitting analogues of
      somatostatin. Despite the use of ultrasound computed tomography and magnetic
      resonance, nuclear medicine techniques remain central to both imaging and therapy
      in thyroid disease and the field has recently become one of the most dynamic
      within the specialty.

PMID- 18083650
TI  - Cytoreductive surgery in ovarian cancer.
AB  - As the overall prognosis for patients with ovarian cancer is poor, the management
      of this condition should be restricted to expert multi-disciplinary teams in
      gynaecological oncology. Apparent early stage ovarian cancer requires accurate
      and complete staging so that potential sites for metastases are not missed.
      Omitting adequate staging may have significant consequences including a negative
      impact on survival rates in young patients. The challenge with advanced ovarian
      cancer is to obtain a detailed appreciation of the extent of disease. This
      information allows treatment with primary chemotherapy if the cancer is
      considered to be inoperable and/or the general condition of the patient renders
      her unfit for appropriate surgery. Available data would suggest that a 5-year
      survival rate of 50% is only possible for those patients who have had complete
      cytoreduction of all tumour. Therefore, the best surgical option for patients
      with advanced ovarian cancer is a 'complete' primary surgical procedure that
      achieves complete clearance of the abdominal cavity rather than 'optimal' surgery
      that leaves tumour nodules up to 1 cm in diameter in situ in the patient.

PMID- 18083651
TI  - Dose-response relationship of ultrasound contrast agent in an in vivo murine
      melanoma model.
AB  - Many factors affect the sensitivity and reliability of tumor vasculature
      assessment at the small doses of contrast agent necessary for imaging mice. In
      this study we investigate the dose-response relationship of ultrasound contrast
      agent for a minimal exposure power Doppler technique (minexPD) in a murine
      melanoma model. K1735 murine melanomas grown in 25 C3H/HeN mice were imaged by
      power Doppler ultrasound using different doses of contrast agents, Optison(R) and
      Definity(R). Six mice were treated with an antivascular agent, combretastatin A4
      phosphate (CA4P), and imaged before and after treatment. The color-weighted
      fractional area (CWFA) of the peak-enhanced image was measured to assess tumor
      perfusion on a relative scale of 0 to 100. CWFA increased logarithmically with
      dose (R(2)=0.97). Treatment with CA4P resulted in pronounced reduction in tumor
      perfusion 2 h after contrast injection, but perfusion recovered in the tumor
      periphery after 2 days. CWFA was significantly different between pre- and post
      treatment for all doses at 2 h and 2 days (p < 0.05, respectively). There was no
      significant difference detectable between the two contrast agents, Optison(R) and
      Definity(R) (p = 0.46). In vivo tumor enhancement in mice increases as
      logarithmic function with dose. Although the extent of enhancement is dose
      dependent, the difference between pre- and post-therapy enhancement is relatively
      unchanged and uniform at varying doses. The two contrast agents tested in this
      study performed equally well. These results suggest that quantitative contrast
      enhanced power Doppler imaging is an effective method for monitoring therapy
      response of tumors in mice.

PMID- 18083652
TI  - Forty years of Equine Veterinary Journal.

PMID- 18083653
TI  - The problem of diagnosing tapeworm infections in horses.

PMID- 18083655
TI  - The effects of chiropractic, massage and phenylbutazone on spinal mechanical
      nociceptive thresholds in horses without clinical signs.
AB  - REASON FOR PERFORMING STUDY: Common methods used to treat back problems in horses
      need to be assessed objectively. OBJECTIVES: To measure spinal mechanical
      nociceptive thresholds (MNTs) and evaluate the effects of chiropractic, massage
      and phenylbutazone, compared with active and inactive control groups. METHODS:
      Baseline MNTs at 7 sites within the thoracolumbar and sacral regions were
      measured in 38 healthy mature horses exhibiting no clinical signs of lumbar pain.
      Horses were assigned to one of 3 treatment groups: instrument-assisted
      chiropractic treatment, therapeutic massage and phenylbutazone; or 2 control
      groups: ridden exercise (active control) or routine paddock turnout with no
      ridden exercise (inactive control). MNT measurements were repeated at 1, 3 and 7
      days post treatment. The percentage change from baseline MNT values was
      calculated within groups. RESULTS: On Day 7, the median MNT had increased by 27,
      12 and 8% in the chiropractic, massage and phenylbutazone groups, respectively.
      MNT changes of <1% were seen within the active and inactive control groups.
      CONCLUSIONS: Chiropractic treatment and massage therapy increased spinal MNTs
      within horses not exhibiting signs of lumbar pain. POTENTIAL RELEVANCE: Pressure
      algometry provides an objective tool to evaluate the effects of commonly used,
      but currently unproven treatment modalities on spinal MNTs. Future studies need
      to evaluate combined treatment effects and longer-term MNT changes in horses with
      documented back pain.

PMID- 18083654
TI  - Lower respiratory tract disease in Thoroughbred racehorses: analysis of
      endoscopic data from a UK training yard.
AB  - REASON FOR PERFORMING STUDY: There has been much research directed at potential
      causative agents and the epidemiology of lower respiratory tract disease (LRTD),
      but few reports of the clinical progression and outcome. OBJECTIVES: To define
      clinical features of LRTD in racehorses, including association with age and
      average duration of disease, through the analysis of endoscopic data. METHODS: A
      retrospective analysis of records from a single training yard of endoscopic
      examinations undertaken over a 2-year period was performed. Horses were subjected
      to regular endoscopic examination for a variety of reasons, and all horses placed
      on antibiotic therapy for lower respiratory tract disease were rescoped following
      treatment. Data analysed included a 0-8 tracheal mucus score based on visible
      endoscopic mucus and gross tracheal lavage turbidity, as well as age and
      treatment duration and type. RESULTS: A total of 522 endoscopic examinations
      undertaken on 123 horses and tracking 169 episodes of lower respiratory tract
      disease were recorded. Mean duration of disease episode was 15.5 days (median =
      11 days, range = 4-61 days). Horses age 2 years were significantly more likely
      than those age > or=3 years to have at least one episode of respiratory disease
      (P<0.001). There was a direct association between initial tracheal mucus score
      and rescope score after treatment. CONCLUSIONS: Lower respiratory tract disease
      was more common in 2-year-olds than in older horses. Affected horses had
      endoscopic evidence of increased tracheal mucus accumulation for an average of
      15.5 days per episode, a considerably shorter period than that suggested by
      previous studies. POTENTIAL RELEVANCE: Endoscopic examinations permit
      longitudinal tracking of lower respiratory tract disease in Thoroughbred
      racehorses. A prolonged duration of disease, sometimes extending for months, can
      be expected in a small proportion of cases, some of which appear to be refractory
      to treatment. There is a clear need for evidence-based analysis of treatment
      regimes to assist clinicians in decision making when managing disease in both
      individual and group situations.

PMID- 18083656
TI  - Treatment of equine cheek teeth by mechanical widening of diastemata in 60 horses
      (2000-2006).
AB  - REASON FOR PERFORMING STUDY: Cheek teeth (CT) diastemata are a significant cause
      of painful dental disease in horses and limited factual information is available
      on the treatment of this disorder. OBJECTIVE: To assess the response to
      mechanical widening in the treatment of diastema. METHOD: Details of the
      presenting signs and treatment of cases of CT diastema by widening were recorded
      and the response to treatment of these cases assessed by re-examinations and by
      obtaining follow-up information from owners. RESULTS: Sixty horses of various
      breeds, median age 9 years, with clinically significant CT diastemata were
      classified as having primary (inadequate rostro-caudal CT compression: n = 29)
      and secondary (to other dental abnormalities: n = 31) diastemata. Quidding was
      present in 82% of cases, weight loss in 35%, halitosis in 17% and bitting
      disorders in 12%; 85% of the identified CT diastemata involved mandibular CT and
      15% maxillary CT, with caudal CT more commonly affected. Of 273 identified
      diastemata in the 60 horses, 207 were deemed to have significantly associated
      periodontal food pocketing and were widened to 4.5-5.5 mm diameter on their
      occlusal surface using a mechanical burr. The 29 horses with primary diastemata
      received a median of 1.3 treatments each and at 10 months following their last
      treatment 72% showed complete remission of signs and 28% showed good improvement.
      The 31 horses with secondary diastemata received a median of 2.2 treatments each
      and, at mean 9 months following their last treatment, 48% showed full
      improvement, 42% good improvement, 6% slight improvement and 3% no improvement.
      Inappropriate areas of the clinical crown were removed from 4 CT without causing
      pulpar exposure; one case was reported to have a transient oral infection post
      treatment and another developed an apical infection in a treated tooth that was
      unrelated to the diastema widening. CONCLUSION: Diastema widening is an effective
      treatment of periodontal pocketing in CT diastemata. POTENTIAL RELEVANCE: The
      described treatment of CT diastema widening by trained personnel is an effective
      and safe treatment, but repeated treatments are often necessary, especially with
      secondary diastemata.

PMID- 18083657
TI  - Epiphyseal cartilage canal blood supply to the tarsus of foals and relationship
      to osteochondrosis.
AB  - REASON FOR PERFORMING STUDY: Pathological changes in the blood supply to growth
      cartilage have been implicated in the pathogenesis of osteochondrosis (OC) in
      horses, but have not been reported using vascular perfusion techniques.
      OBJECTIVE: To describe the developmental pattern of cartilage canal vessels in
      the distal tibial epiphysis and talar growth cartilage of foals. METHODS: Nine
      foals bred from parents with OC were sacrificed between the ages of 0 and 7 weeks
      to undergo a barium perfusion procedure. The distal end of the tibia and the
      entire talus were cleared in methyl salicylate and perfused vessels studied in
      the intact bones. Slabs with a thickness of 4-5 mm from 3 predilection sites for
      OC were examined in the stereomicroscope and with light microscopy. RESULTS:
      Cartilage canals were present for a limited period of growth. Perfused vessels
      initially entered canals from the perichondrium. Vessels in the proximal portion
      of canals retained their perichondrial arterial source throughout. With time, the
      ossification front advanced to incorporate the mid-portion of canals; and
      anastomoses formed between canal vessels and subchondral vessels. A shift
      occurred and vessels in the distal terminus of canals came to use subchondral
      vessels as their arterial source. Twelve histological lesions were found in 7
      foals. All contained necrotic vessels surrounded by necrotic growth cartilage and
      3 caused macroscopically visible delay in endochondral ossification. Lesions were
      located where vessels traversed the ossification front to enter the distal
      terminus of canals. CONCLUSION: Cartilage canal vessels are particularly
      susceptible to failure at the point where they cross the ossification front, with
      consequences for the viability of those chondrocytes that depend on them.
      POTENTIAL RELEVANCE: A better understanding of how lesions of OC arise may
      improve the ability to identify, monitor, prevent and treat this disorder.
      Involvement of cartilage canals in the pathogenesis of equine tarsal OC plausibly
      explains several clinical features of this disease.

PMID- 18083658
TI  - The effect of omeprazole paste on intragastric pH in clinically ill neonatal
      foals.
AB  - REASON FOR PERFORMING STUDY: Administration of omeprazole paste per os to healthy
      neonatal foals has been shown to effectively increase intragastric pH, but has
      not been evaluated in sick neonatal foals. OBJECTIVES: To determine the effect of
      orally administered omeprazole paste on intragastric pH in clinically ill
      neonatal foals requiring nasogastric intubation. METHODS: Intragastric pH was
      measured continuously for 24 h using an indwelling electrode and continuous data
      recording system in hospitalised neonatal foals age < or =2 days. Intragastric pH
      was measured for 12 h prior to (pretreatment period) and 12 h following (post
      treatment period) treatment with omeprazole paste (4 mg/kg bwt per os). All foals
      displayed periods of acidity (pH <4) prior to treatment. Statistical analysis
      compared pre- and post treatment mean and median intragastric pH, and percentage
      of time below pH 4. RESULTS: Eight foals were evaluated age 1-3 days, a
      gestational age of at least 320 days or reported to be full term. The mean (3.19
      +/- 1.50 vs. 6.20 +/- 0.93) and median (4.6 +/- 1.7 vs. 6.86 +/- 0.89) pH were
      significantly higher and the percentage of time below pH 4 (32.25 vs. 1.1%) was
      significantly lower in the post treatment compared to the pretreatment period.
      CONCLUSION: Omeprazole paste effectively increases intragastric pH in clinically
      ill neonatal foals after one dose at 4 mg/kg bwt orally.

PMID- 18083659
TI  - Effects of a calm companion on fear reactions in naive test horses.
AB  - REASON FOR PERFORMING STUDY: In fear-eliciting situations, horses tend to show
      flight reactions that can be dangerous for both horse and man. Finding
      appropriate methods for reducing fearfulness in horses has important practical
      implications. OBJECTIVES: To investigate whether the presence of a calm companion
      horse influences fear reactions in naive subject horses. HYPOTHESES: The presence
      of a habituated (calm) companion horse in a fear-eliciting situation can reduce
      fear reactions in naive subject horses, compared to subject horses with a
      nonhabituated companion (control). METHODS: Minimally handled (n = 36), 2-year
      old stallions were used, 18 as subjects and 18 as companions. Companion horses (n
      = 9) were habituated to an otherwise frightening, standardised test stimulus
      (calm companions), whereas the rest (n = 9) of the companion horses remained
      nonhabituated (control companions). During the test, unique pairs of companion
      and subject horses were exposed to the test stimulus while heart rate and
      behavioural responses were registered. Subsequently, subject horses were exposed
      to the stimulus on their own (post test). RESULTS: Subject horses, paired with a
      calm companion horse, showed less fear-related behaviour and lower heart rate
      responses compared to subject horses with control companions. Results from the
      post test suggest that the difference between treatment groups remained in the
      subsequent absence of companion horses. CONCLUSIONS AND POTENTIAL RELEVANCE: It
      appears possible to reduce fear reactions in young, naive horses by allowing them
      to interact with a calm companion horse in fear-eliciting situations.

PMID- 18083660
TI  - Effects of a commercial dose of L-tryptophan on plasma tryptophan concentrations
      and behaviour in horses.
AB  - REASON FOR PERFORMING STUDY: L-tryptophan is a common ingredient in equine
      calmative products, but its effectiveness has not been demonstrated in horses.
      HYPOTHESIS: To determine whether a commercial dose of L-tryptophan increases
      plasma tryptophan and alters behaviour in horses fed a roughage or concentrate
      meal. METHODS: L-tryptophan (6.3 g) or placebo (water) was administered per os in
      a cross-over design, to 12 Thoroughbred horses (503 +/- 12.1 kg bwt), just before
      a meal of lucerne hay or oats. Plasma tryptophan was measured by gas
      chromatography. Horse behaviour was observed in an empty enclosure, then in the
      presence of an unfamiliar person and a novel object. RESULTS: Total plasma
      tryptophan increased 3-fold in both studies, peaking 1.5-2 h after dosing. After
      the peak, tryptophan remained high for several hours if the horses had been fed
      hay, but fell sharply if fed oats, consistent with the glycaemic responses to
      these meals. However, the ratio of tryptophan to 4 large neutral amino acids
      (phenylalanine, tyrosine, leucine and isoleucine) increased in the tryptophan
      treated horses to a similar extent and for a similar duration, with both diets.
      The presence of a stranger or novel object increased heart rate (P<0.05), but
      caused no behavioural effects that were altered by tryptophan, regardless of the
      diet. CONCLUSIONS: Plasma tryptophan increases when tryptophan is administered at
      a dose used in some commercial products, but this is not reflected by marked
      behavioural changes in the horse. POTENTIAL RELEVANCE: Further work is required
      to refine behavioural tests and identify an effective dose of L-tryptophan in the
      horse.

PMID- 18083661
TI  - Radiographic, scintigraphic and magnetic resonance imaging findings in the palmar
      processes of the distal phalanx.
AB  - REASON FOR PERFORMING STUDY: Increased radiopharmaceutical uptake (IRU) in the
      palmar processes of the distal phalanx is recognised but its clinical
      significance has not been established. OBJECTIVES: To investigate the
      relationship between radiographic, scintigraphic and MRI findings in the palmar
      processes of the distal phalanx. HYPOTHESES: Increased radiopharmaceutical uptake
      in the palmar processes of the distal phalanx is associated with MRI
      abnormalities; IRU and MRI abnormalities are over-represented in lame limbs.
      METHODS: Clinical data, radiographic, scintigraphic and MRI findings of 258
      horses with unilateral or bilateral foot pain were recorded. Scintigraphic images
      were assessed subjectively and using region of interest and profile analysis, and
      intensity of IRU graded. Alteration in signal intensity in T1 and T2 weighted and
      short tau inversion recovery (STIR) MR images was documented, and MRI
      abnormalities graded. Relationships between scintigraphic, MRI, radiographic and
      clinical findings were assessed. RESULTS: Focal IRU was over-represented in
      palmar processes with most MRI abnormalities. There was a significant correlation
      between IRU and MRI grades and IRU was over-represented in palmar processes with
      MRI Grades 2 and 3. Both IRU and MRI abnormalities occurred most frequently in
      the medial palmar process. MRI abnormalities were generally over-represented in
      lame limbs. The most common MRI abnormality was mild diffuse decreased signal
      intensity in T1 and T2 weighted images, which was associated with mild
      generalised IRU. CONCLUSIONS: There was considerable variation in the
      radiographic, scintigraphic and MRI appearance of palmar processes of the distal
      phalanx. Focal IRU in a palmar process was seen in association with MRI
      abnormalities and lameness or as an incidental finding. Magnetic resonance
      imaging abnormalities occurred more frequently in lame limbs, either contributing
      to lameness or as a consequence of lameness. POTENTIAL RELEVANCE: Further
      investigation is needed to establish the clinical significance of MRI
      abnormalities in the palmar processes of the distal phalanx and their
      relationship with lesions in adjacent structures.

PMID- 18083662
TI  - Plasma aldosterone, vasopressin and atrial natriuretic peptide in hypovolaemia: a
      preliminary comparative study of neonatal and mature horses.
AB  - REASON FOR PERFORMING STUDY: Neonatal foals succumb rapidly to hypovolaemic shock
      in comparison to mature horses; they do not consistently increase their heart
      rate in response to hypotension and respond differently to fluid administration.
      The hormonal responses to hypovolaemia in the horse and foal require
      investigation. HYPOTHESIS: The hormonal responses to hypovolaemia and fluid
      administration differ between mature and neonatal horses. METHODS: Five mature
      horses and 5 neonatal foals fulfilling predetermined criteria for hypovolaemia,
      were included in the study. A blood sample was taken at admission and after
      normalisation of fluid balance. These were analysed for plasma aldosterone,
      vasopressin (AVP) and atrial natriuretic peptide (ANP). Normally distributed
      variables were compared using the Student's t test and nonparametric data using
      the Mann-Whitney U test. RESULTS: ANP, AVP and aldosterone were higher before
      fluid resuscitation than after fluid resuscitation in mature horses. Aldosterone
      was higher before than after fluid resuscitation in foals, and was higher in
      foals both before and after fluid resuscitation than in mature horses. ANP was
      lower in mature horses after fluid resuscitation than in foals. No other
      comparisons were significantly different. CONCLUSIONS: The hormonal responses of
      the mature and neonatal horses are different during hypovolaemia and following
      fluid resuscitation. POTENTIAL RELEVANCE: The differences in the hormonal
      responses to hypovolaemia and fluid resuscitation may be important when
      considering fluid resuscitation of hypovolaemic horses and foals, and warrants
      further investigation.

PMID- 18083663
TI  - Neuroanatomy of the equine dorsal cricoarytenoid muscle: surgical implications.
AB  - REASON FOR PERFORMING STUDY: Studies are required to define more accurately and
      completely the neuroanatomy of the equine dorsal cricoarytenoid muscle as a
      prerequisite for developing a neuroprosthesis for recurrent laryngeal neuropathy.
      OBJECTIVES: To describe the anatomy, innervation, fibre types and function of the
      equine dorsal cricoarytenoid muscle. METHODS: Thirty-one larynges were collected
      at necropsy from horses with no history of upper airway disease and 25 subjected
      to gross dissection. Thereafter, the following preparations were made on a subset
      of larynges: histochemical staining (n = 5), Sihler's and acetylcholinesterase
      staining for motor endplates (n = 2). An additional 6 larynges were collected and
      used for a muscle stimulation study. RESULTS: Two neuromuscular compartments
      (NMC), each innervated by a primary nerve branch of the recurrent laryngeal
      nerve, were identified in all larynges. Stimulation of the lateral NMC produced
      more lateral displacement of the arytenoid cartilage than the medial NMC
      (P<0.05). The medial NMC tended to rotate the arytenoid cartilage dorsally. Motor
      endplates were identified at the junction of the middle and caudal thirds of each
      NMC. If fibre type grouping was present it was always present in both NMCs.
      CONCLUSIONS: The equine dorsal cricoarytenoid muscle has 2 distinct muscle NMCs
      with discrete innervation and lines of action. The lateral NMC appears to have a
      larger role in increasing cross-sectional area of the rima glottidis. POTENTIAL
      RELEVANCE: This information should assist in planning surgical reinnervation
      procedures and development of a neuroprosthesis for recurrent laryngeal
      neuropathy.

PMID- 18083664
TI  - Liposome-mediated uptake of exogenous DNA by equine spermatozoa and applications
      in sperm-mediated gene transfer.
AB  - REASON FOR PERFORMING STUDY: Sperm-mediated gene transfer has been reported as a
      method for production of transgenic animals in a variety of species, and this
      technique represents a possible method for production of transgenic equids.
      OBJECTIVES: To evaluate the uptake of exogenous DNA (enhanced green fluorescent
      protein; pEGFP) by equine spermatozoa and to assess the ability of transfected
      spermatozoa to introduce this transgene into early equine embryos. METHODS: To
      evaluate incorporation of pEGFP into equine spermatozoa, washed spermatozoa were
      incubated with 32P-pEGFP, with or without lipofection. Spermatozoa were also
      transfected with fluorescently-labelled DNA (Alexa647-pEGFP) and changes in sperm
      viability and DNA uptake were assessed. Mares were inseminated with pEGFP
      transfected spermatozoa and embryos recovered. Expression of pEGFP was assessed
      by epifluorescence microscopy of embryos, and the presence of pEGFP DNA and mRNA
      was assessed by PCR and RT-PCR, respectively. RESULTS: Liposome-mediated
      transfection increased the incorporation of 32P-pEGFP into spermatozoa compared
      to controls. Flow cytometric evaluation of spermatozoa after transfection with
      Alexa647-pEGFP revealed a linear increase in the proportion of live, Alexa647+
      spermatozoa with increasing DNA concentrations. After insemination with
      transfected spermatozoa, 8 embryos were recovered. There was no evidence of EGFP
      expression in the recovered embryos; however, PCR analysis revealed evidence of
      the pEGFP transgene in 2 of 5 embryos analysed. CONCLUSIONS: The incorporation of
      exogenous DNA by equine spermatozoa was enhanced by liposome-mediated
      transfection and this did not adversely affect sperm viability, acrosomal
      integrity or fertility. Although the EGFP transgene was detected in a proportion
      of Day 7-10 embryos, there was no evidence of expression of EGFP in these
      embryos. POTENTIAL RELEVANCE: Sperm-mediated gene transfer offers a potential
      technique for the generation of transgenic equids.

PMID- 18083665
TI  - Current guidelines on good reporting of analytical observational studies in
      epidemiology.

PMID- 18083666
TI  - Equine travellers to the Olympic Games in Hong Kong 2008: a review of worldwide
      challenges to equine health, with particular reference to vector-borne diseases.
AB  - The past 10-20 years have seen exponential growth in the volume of trade in
      horses and equine germplasm; and the extent of global horse movements has
      increased significantly in the last 4 years. In preparing for the transport of
      elite Olympic horses to Hong Kong in 2008, it will be very important to be as
      fully informed as possible of the disease situation in both the exporting and
      importing country, import and re-entry requirements, as well as having a
      vaccination strategy to protect against particular diseases. In this context the
      review describes the equine vector-borne disease situation in Europe, Asia,
      Africa and South America and provides estimates of the number of horse movements
      between these countries, as well as information on import requirements and
      vaccination strategies.

PMID- 18083667
TI  - A review of the cost-effectiveness of face-to-face behavioural interventions for
      smoking, physical activity, diet and alcohol.
AB  - OBJECTIVE: To assess the evidence for the cost-effectiveness of health behaviour
      interventions that address the major behavioural risk factors for chronic
      disease, including smoking, physical inactivity, poor diet, and alcohol misuse.
      METHODS: Medical and economic databases were searched for relevant economic
      evaluations. Studies were critically appraised using a published 35-point
      checklist, and the results are described using a narrative approach, noting
      methodological limitations. The review included 64 studies from 1995-2005,
      including 17 reports on multiple behaviour interventions. RESULTS: There was
      considerable variation among the studies by target populations, intervention
      components, primary outcomes, and economic methods, but the reported incremental
      cost-effectiveness ratios were consistently low (e.g. <14,000 Euros per quality
      adjusted life-year gained for smoking-cessation programmes in 2006 Euros) as
      compared to certain preventive pharmaceutical and invasive interventions.
      Interventions targeting high-risk-population subgroups were relatively better
      value for money as compared to those targeting general populations. DISCUSSION:
      In general, the results of this review demonstrate favourable cost-effectiveness
      for smoking interventions, physical activity interventions and multiple behaviour
      interventions in high-risk groups. Although alcohol and dietary interventions
      appeared to be economically favourable, it is difficult to draw conclusions
      because of the variety in study outcomes. However, methodological limitations
      weaken the generalizability of findings, and suggest that the results of any
      given study should be considered carefully when being used to inform resource
      allocation.

PMID- 18083668
TI  - Transfer of care for outpatients with stable chronic obstructive pulmonary
      disease from respiratory care physician to respiratory nurse--a randomized
      controlled study.
AB  - OBJECTIVES: To assess effects on patient outcomes when care for patients with
      stable chronic obstructive pulmonary disease (COPD) is transferred from
      respiratory care physician to respiratory nurse. METHODS: A randomized controlled
      trial was used with a follow-up period of 9 months. Of 720 patients from the
      respiratory outpatient clinic of the general and teaching hospital in Alkmaar
      (The Netherlands), 187 were eligible for randomization and gave informed consent.
      Ninety-three patients received care from the nurse, and 87 received usual care.
      Outcomes measured were: clinical parameters, health status, self-care behaviour
      (including knowledge), patient satisfaction, and consultations with key care
      providers. RESULTS: The respiratory nurse reported more consultations than the
      respiratory care physician [mean (standard deviation)]: number of consultations
      3.1 (0.7) by nurse and 2.0 (0.9) by physician (p = 0.007). Patients cared for by
      the nurse showed worsening in mean forced vital capacity [-5.5% (13.3%) v. +2.9%
      (18.2%) with physician; p = 0.004], and no difference in self-assessed condition,
      while improvements were found for subjective knowledge (p = 0.017), self-assessed
      rate for coping with COPD (p = 0.045), overall satisfaction (p = 0.003), and the
      majority of individual indicators of satisfaction. Groups showed no differences
      for forced expiratory volume in 1 s, body mass index, smoking status, health
      status, objective knowledge, other items of self-care behaviour, and
      consultations with key care providers. DISCUSSION: Assignment of care for
      outpatients with stable COPD to the respiratory nurse, working under a protocol,
      seems to be justified in terms of patient outcomes.

PMID- 18083669
TI  - The physical, social and psychological impact of priapism on adult males with
      sickle cell disorder.
AB  - Priapism is defined as prolonged and painful penile erection that does not
      subside on orgasm. It is considered to be a urological emergency. However,
      patients do not always seek prompt medical help. The incidence of priapism is
      increased by sickle cell disease, where it is a complication of the
      characteristic sickling of the red blood cells. Little is known about the
      psychological or social implications of this complication or the strategies that
      sickle cell patients use to manage it. A qualitative study was carried out in
      order to investigate these topics. Semi-structured interviews were carried out
      with adult male patients of the Sickle Cell and Thalassaemia Centre in Birmingham
      in the UK who experienced priapism. These were subsequently analysed using
      grounded theory. Ten themes were elicited: first occurrence of priapism, pain,
      precipitants, emotional consequences, self-management, experience of hospital,
      impact on work and social life, impact on sexual relationships, erectile
      dysfunction, and disclosure. The dominant experiences were ones of despair,
      embarrassment, and isolation. Participants described finding it difficult to
      disclose priapism, with the result that it was often unreported until late in its
      course. Attempts to manage priapism at home varied, with there being little
      consensus on their efficacy. The results are discussed with respect to the
      healthcare services that cater for these patients.

PMID- 18083670
TI  - Living and working with sickness: a qualitative study.
AB  - OBJECTIVES: To explore patients' views and experiences of long-term sickness
      absence, and their attitudes with regard to return to work. METHODS: The study
      design and analysis were guided by a narrative psychology perspective. In-depth,
      biographical narrative interviews were conducted with 26 individuals, aged
      between 30 and 65 years, who had been certified absent for longer than 6 weeks.
      Follow-up data were collected at 12 months. The narrative analysis techniques
      used were holistic content, holistic form, categorical content, and categorical
      form. This paper illustrates our findings obtained mainly using the holistic-form
      approach. RESULTS: Long-term absence reduces attachment to work and impacts on
      work identity. Three distinct narrative patterns emerged from the data analysis.
      The first was 'uncomplicated absence', usually triggered by an acute event with
      an uncomplicated resolution; the second, 'complicated absence', typically
      involved gradually deteriorating health and social complications with a less
      predictable recovery; the third pattern, 'sustained absence', was associated with
      chronic deterioration in health, often complex and multidimensional in nature.
      These three patterns offer an insight into how well individuals are coping with
      their underlying health condition. CONCLUSIONS: Narrative analysis tools could be
      developed to help identify those patients who would: (1) respond favourably to
      'return to work' interventions; or (2) benefit from additional health service
      support.

PMID- 18083671
TI  - Supporting self-management for patients with complex medical needs:
      recommendations of a working group.
AB  - Increasing numbers of persons live with complex chronic medical needs and are at
      risk for poor health outcomes. These patients require unique self-management
      support, as they must manage many, often interacting, tasks. As part of a
      conference on Managing Complexity in Chronic Care sponsored by the Department of
      Veterans Affairs, a working group was convened to consider self-management issues
      specific to complex chronic care. In this paper, we assess gaps in current
      knowledge on self-management support relevant to this population, report on the
      recommendations of our working group, and discuss directions for future study. We
      conclude that this population requires specialized, multidimensional self
      management support to achieve a range of patient-centred goals. New technologies
      and models of care delivery may provide opportunities to develop this support.
      Validation and quantification of these processes will require the development of
      performance measures that reflect the needs of this population, and research to
      prove effectiveness.

PMID- 18083672
TI  - Improving management of chronic illness in the National Health Service: better
      incentives are the key.

PMID- 18083673
TI  - What should be incentivized in care of chronic illness?

PMID- 18083674
TI  - Improving management of chronic illness: better identification of effective
      interventions for high risk patients is needed.

PMID- 18083675
TI  - Improving management of chronic illness in the National Health Service: are
      better incentives really the key?

PMID- 18083677
TI  - Multiple chronic diseases and quality of life: patterns emerging from a large
      national sample, Australia.
AB  - OBJECTIVES: To assess the importance of multiple chronic diseases (co
      morbidities) to how people feel about their lives generally. To do this, we
      studied the associations between co-morbidities and indicators of quality of life
      and/or psychological distress. METHODS: Analysis of unit record cross-sectional
      data from Australian national surveys for the population aged 20 years or more.
      Identification of an appropriate indicator of multiple chronic diseases (i.e. co
      morbidities). Use of logistic regression techniques to study associations
      between: (1) co-morbidities and demographic, socio-economic and risk factor
      variables; and (2) quality of life (general and psychological distress) and
      demographic, socio-economic and health status indicators. RESULTS: Older people,
      obese persons, women, persons with low socio-economic status and those living
      alone had significantly greater probability of having three or more chronic
      illnesses than did other people aged 20+ years (p<0.0001). Also, people with co
      morbidities and/or with poor self-rated general health, those living alone,
      people with low educational qualifications and persons with low socio-economic
      status were more likely to feel dissatisfied, unhappy or terrible about their
      lives and to have moderate, high or very high psychological distress scores than
      the rest of the 20+-year-old population (p<0.0001). CONCLUSIONS: Multiple chronic
      diseases were found to have a considerable negative impact on quality of life,
      not only in terms of how people felt about their lives generally, but also in
      terms of the extent of their psychological distress.

PMID- 18083678
TI  - Anxiety and health-related quality of life of patients undergoing total hip
      arthroplasty for osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis in a hip not only causes pain and decreases physical
      function, which are the most common reasons for total hip arthroplasty, but also
      causes anxiety and reduces patients' health-related quality of life (HRQoL). The
      objective of this study was to evaluate patients' anxiety and its possible
      relationship with HRQoL before and after surgery. METHODS: In this longitudinal
      follow-up study, the State Trait Anxiety Inventory was used to measure patients'
      (n = 100) level of anxiety before surgery and at 1 month, 3 months and 6 months
      post-operatively. The Sickness Impact Profile was used to measure patients' total
      HRQoL before surgery and post-operatively at 3 and 6 months. RESULTS: Before
      surgery, patients' trait and state anxiety were moderate. Patients' pre-operative
      trait anxiety impaired HRQoL both before and after surgery. After surgery, state
      anxiety remained at a moderate level, although a few minor peaks were observed,
      but no relationship between state anxiety and HRQoL was found. DISCUSSION:
      Patients' needs and characteristics should be carefully assessed when planning
      post-operative care and support. Nurses should be aware of factors that may
      relate to anxiety and also consider different methods of supporting patients'
      recovery.

PMID- 18083679
TI  - Diabetes and the risk of tuberculosis: a neglected threat to public health?
AB  - OBJECTIVES: Tuberculosis (TB) remains a major global public health problem. In
      the past, a relationship between TB and diabetes mellitus (DM) was recognized,
      and its importance was acknowledged through joint treatment clinics. However,
      this is rarely highlighted in current research or control priorities. This paper
      aims to evaluate the evidence for an association between these two diseases.
      METHODS: A Medline literature search was undertaken, supplemented by checking
      references and contacting experts. We critically appraised studies that
      quantified the association between TB and DM, and were published after 1995. We
      assessed study quality according to criteria such as sample size, method of
      selection of cases and controls, losses to follow-up, quality and method of
      control of confounding, and summarized the results narratively and in tabular
      form. RESULTS: All studies identified statistically significant and clinically
      important associations, with the increase in risk or odds of TB varying between
      1.5- and 7.8-fold for those with DM. Risk was highest at younger ages. Most
      studies had not measured and controlled adequately for potential major
      confounders. DISCUSSION: There is strong evidence for an association between TB
      and DM, which has potential public health implications. Further well-designed
      studies are needed to assess the magnitude precisely.

PMID- 18083680
TI  - Between remission and cure: patients, practitioners and the transformation of
      leukaemia in the late twentieth century.
AB  - OBJECTIVES: During the course of the 1960s and 1970s, acute leukaemia in
      childhood ceased to be invariably fatal and was recategorized as curable. The
      meaning of cure in this case, however, was problematic, as it was impossible for
      physicians to be certain that cancer would not return. This paper uses historical
      methods to explore how remission was understood by families with children with
      acute leukaemia during the period in which the first cures were announced,
      roughly 1972-77. METHODS: These comprised documentary analysis of records of the
      Medical Research Council's leukaemia working parties, published papers and
      letters on treatments for childhood leukaemia, and interviews with eight UK
      paediatric oncologists practising in UK hospitals in the 1960s and 1970s.
      RESULTS: Two approaches to defining 'cure' in leukaemia can be identified. The
      first relied on statistical assessment of survival rates. I argue that the
      concept of 'indefinite remission' came to serve for researchers and clinicians as
      a proxy measure of cure. However, the concept of 'indefinite remission' left many
      patients and their families quite uncertain as to whether a cure had really
      happened. A second approach to defining cure therefore developed. Faced with
      uncertainty, patients, parents and psychologists sought to develop alternative
      measures of success--including the notion of 'psychological cure'--that brought
      forward the moment of cure and its relief. CONCLUSIONS: Changing
      conceptualizations of leukaemia shaped and were shaped by negotiations over the
      meaning of 'remission' and 'cure'. On the one hand, the statistical definition of
      cure was not available for years. On the other hand, psychological cure could
      begin from the time of first remission, even if medical absolution was not
      available for years.

PMID- 18083681
TI  - The biographical impact of teenage and adolescent cancer.
AB  - OBJECTIVES: This paper offers an overview of the findings of research into the
      experience of having cancer in adolescence and young adulthood, the aims of which
      were to understand how age and life stage affect the illness experience and
      impact upon biographies and life trajectories. METHODS: The data were gathered
      primarily through the use of in-depth qualitative interviews with adolescents and
      young adults with cancer, but also through the submission of a small number of
      written narratives. RESULTS: Acute and life-threatening illness at a transitional
      life stage on the threshold of adulthood can have a long-term, and therefore
      chronic, effect on the life trajectories and biographies of young adult cancer
      patients. Many aspects of the participants' lives were affected, including
      education, careers, life plans, friendship networks, appearance, sexuality and
      fertility. The economic effects could also be far-reaching and contribute to a
      loss of independence, which is very fragile in this age-group. CONCLUSIONS: While
      recognizing the potentially devastating impact of cancer at any age, the research
      findings suggest a distinct effect in adolescence and young adulthood resulting
      from a disrupted biography at a critical transitional moment in the life
      trajectory that can have a chronic effect after the acute stage of the illness is
      passed. An age-appropriate approach to the care of young people with cancer that
      takes into account the distinct effects of life stage in this age-group can
      mitigate the negative impact on life trajectories and maximize the chances of
      adherence and a return to normal life after recovery.

PMID- 18083682
TI  - 'Having cancer changed my life, and changed my life forever': survival, illness
      legacy and service provision following cancer in childhood.
AB  - OBJECTIVES: To explore how having cancer in childhood influences social and
      personal wellbeing in young adulthood. METHODS: Questionnaires (55) eliciting
      lengthy written responses and in-depth interviews (32) were used with male and
      female survivors of cancer in childhood (aged between 18 and 28 years). Analysis
      drew on a combination of grounded-theory techniques and narrative analysis.
      RESULTS: Three key areas are outlined relating to the characterization of
      survivorship by participants. These include highlighting survival as not
      necessarily a simple end to a cancer story, issues relating to post-cancer bodily
      self-concept and its gendering, and, efforts at managing uncertainties through
      medical interactions and information gathering. DISCUSSION: Participant stories
      in this study illustrate that even in long-term survival, cancer is present as a
      web of ongoing influences from the original disease and treatment, as well as the
      social and personal aftershocks that can occur well after malignant cells have
      been controlled. Findings highlight the necessity for complex redevelopment of
      healthcare services and social support provisions for this growing population.

PMID- 18083683
TI  - Poking Pandora in the eye.

PMID- 18083684
TI  - The parents' story.

PMID- 18083685
TI  - Towards a new era of tissue-based diagnosis and research.
AB  - Molecular investigation of tissue obtained from patients with many chronic
      illnesses is becoming increasingly important. Using the example of childhood
      cancer, we show how such investigations contribute in important ways to
      understanding the underlying pathophysiological basis of disease, determining
      optimal patient management, and identifying targets for potential new novel
      therapeutic approaches. Tissue banks are now recognized as an important resource
      for biomedical research in this area. Challenges for the future of tissue-banking
      include formalization of technical matters, including the generation of standard
      operating procedures and quality-control methods. More complex challenges attend
      the legal and ethical issues in tissue banking. Notwithstanding recent UK
      legislation, there are many legal uncertainties. Use of excised tissue in
      research is often claimed to raise a range of ethical issues, but it is not at
      all clear that public confidence and support for tissue-based research is as
      negative as some accounts in the socio-anthropological and ethical literature
      would suggest. Nonetheless, ensuring confidence and trust in tissue-banking will
      remain an important objective, and the possibilities of novel governance
      structures should be explored.

PMID- 18083686
TI  - Relations between Internet use, socio-economic status (SES), social support and
      subjective health.
AB  - This study aimed to explore relations between Internet use, socio-economic status
      (SES), social support and subjective health. Participants were from
      representative samples between 15 and 80 years of age from seven different
      European countries. Two different survey datasets were used: (i) eHealth trends
      (eHT; N = 7934) and (ii) the European social survey (ESS2; N = 11248). Internet
      users who had used the Internet for health purposes were compared with Internet
      users who had not used it for health purposes. Structural equation modelling was
      used to assess the relationships between SES, Internet use, social support and
      subjective health. Use of other media was compared to Internet use in relation to
      social support and subjective health. Internet use was found to be more closely
      related to social support and subjective health than use of other media. Internet
      use was also found to be a plausible mediator between SES and subjective health,
      especially through interacting with social support.

PMID- 18083687
TI  - Promoting health in response to global tourism expansion in Cuba.
AB  - The ability of communities to respond to the pressures of globalization is an
      important determinant of community health. Tourism is a rapidly growing industry
      and there is an increasing concern about its health impact on local communities.
      Nonetheless, little research has been conducted to identify potential mitigating
      measures. We therefore took advantage of the 'natural experiment' provided by the
      expansion of tourism in Cuba, and conducted four focus groups and key informants
      interviews in each of two coastal communities. Participants expressed concerns
      about psycho-social impacts as well as occupational and environmental concerns,
      and both infectious and chronic diseases. A wide array of programs that had been
      developed to mitigate potential negative were described. Some of the programs
      were national in scope and others were locally developed. The programs
      particularly targeted youth as the most vulnerable population at risk of
      addictions and sexually transmitted infections. Occupational health concerns for
      workers in the tourism sector were also addressed, with many of the measures
      implemented protecting tourists as well. The health promotion and various other
      participatory action initiatives implemented showed a strong commitment to
      address the impacts of tourism and also contributed to building capacity in the
      two communities. Although longitudinal studies are needed to assess the
      sustainability of these programs and to evaluate their long-term impact in
      protecting health, other communities can learn from the initiatives taken.

PMID- 18083688
TI  - Interlaboratory performance of a microarray-based gene expression test to
      determine tissue of origin in poorly differentiated and undifferentiated cancers.
AB  - Clinical workup of metastatic malignancies of unknown origin is often arduous and
      expensive and is reported to be unsuccessful in 30 to 60% of cases. Accurate
      classification of uncertain primary cancers may improve with microarray-based
      gene expression testing. We evaluated the analytical performance characteristics
      of the Pathwork tissue of origin test, which uses expression signals from 1668
      probe sets in a gene expression microarray, to quantify the similarity of tumor
      specimens to 15 known tissues of origin. Sixty archived tissue specimens from
      poorly and undifferentiated tumors (metastatic and primary) were analyzed at four
      laboratories representing a wide range of preanalytical conditions (eg,
      personnel, reagents, instrumentation, and protocols). Cross-laboratory
      comparisons showed highly reproducible results between laboratories, with
      correlation coefficients between 0.95 to 0.97 for measurements of similarity
      scores, and an average 93.8% overall concordance between laboratories in terms of
      final tissue calls. Bland-Altman plots (mean coefficients of reproducibility of
      32.48+/-3.97) and kappa statistics (kappa >0.86) also indicated a high level of
      agreement between laboratories. We conclude that the Pathwork tissue of origin
      test is a robust assay that produces consistent results in diverse laboratory
      conditions reflecting the preanalytical variations found in the everyday clinical
      practice of molecular diagnostics laboratories.

PMID- 18083689
TI  - Cost of neutropenic complications of chemotherapy.
AB  - BACKGROUND: Cost of neutropenic complications of myelosuppressive chemotherapy
      has been reported to be substantial. Prior research, however, has focused on
      initial hospitalization only and has failed to account for follow-on care.
      PATIENTS AND METHODS: Using a US health-care claims database, all adult cancer
      patients who received a course of chemotherapy were identified. For each such
      patient, each unique cycle of chemotherapy within the course and each occurrence
      of neutropenic complications within these cycles were characterized. Patients
      developing neutropenic complications in a given cycle (neutropenia patients),
      starting with the first, were matched (1:1) to those who did not develop
      neutropenic complications in that cycle (comparison patients), and health-care
      costs (i.e. expenditures) were tallied for each matched pair. RESULTS:
      Neutropenia patients (n = 373) and comparison patients were similar in terms of
      baseline characteristics. Costs of neutropenia-related care were $12,397 (95%
      confidence interval $10,274-$14,754) higher for neutropenia versus comparison
      patients [$14,407 ($12,357-$16,743) versus $2010 ($1490-$2553)]. Among
      neutropenia patients, mean cost of initial hospitalization for neutropenic
      complications was $7813 ($6537-$9379); cost of all subsequent neutropenia-related
      care averaged $6594 ($5217-$8272). CONCLUSIONS: Neutropenic complications of
      myelosuppressive chemotherapy are costly. Prior research focusing on initial
      hospitalization only may have underestimated the cost of these complications by
      as much as 40%.

PMID- 18083690
TI  - The addition of rituximab to CHOP chemotherapy improves overall and failure-free
      survival for follicular grade 3 lymphoma.
AB  - BACKGROUND: The benefit of adding rituximab to anthracycline-based therapy for
      follicular lymphoma grade 3 has not been studied. PATIENTS AND METHODS: We
      retrospectively reviewed the records of 45 patients with follicular grade 3
      lymphoma who were treated with rituximab and the combination of cyclophosphamide,
      doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD
      Anderson Cancer Center. Response rate, failure-free survival (FFS), and overall
      survival (OS) were estimated and a historical comparison to CHOP-only-treated
      patients was made. RESULTS: The International Prognostic Index (IPI) distribution
      was 47% low, 36% low intermediate, 13% high intermediate, and 4% high risk. The
      complete response rate was 96%. Forty-four of 45 patients are still alive. Median
      follow-up for the alive patients is 3.5 years. The 3-year FFS rate according to
      the IPI was 80% [95% confidence interval (CI) 64% to 100%] in low, 81% in low
      intermediate (95% CI 64% to 100%), and 50% (95% CI 25% to 100%) in high
      intermediate/high-risk patient group. The addition of rituximab to CHOP improved
      both 5-year FFS, 71% (95% CI 58% to 87%) compared with 44% (95% CI 36% to 55%)
      with P value of 0.019, and 5-year OS, 98% (95% CI 93% to 100%) compared with 75%
      (95% CI 67% to 84%) with P value of 0.0034. CONCLUSION: The addition of rituximab
      to CHOP provided a high response rate and excellent early survival. Poor-risk
      patients continue to demonstrate a high rate of failure despite the use of
      rituximab.

PMID- 18083691
TI  - Randomized phase II study of irinotecan, leucovorin and 5-fluorouracil (ILF)
      versus cisplatin plus ILF (PILF) combination chemotherapy for advanced gastric
      cancer.
AB  - BACKGROUND: Irinotecan, in combination with 5-fluorouracil (5-FU) or cisplatin,
      has demonstrated efficacy against advanced gastric cancer (AGC). PATIENTS AND
      METHODS: Chemotherapy-naive AGC patients were randomly assigned to receive
      irinotecan 150 mg/m(2) on day 1, leucovorin 20 mg/m(2) and a 22-h infusion of 5
      FU 1000 mg/m(2) on days 1 and 2 (ILF) or ILF plus cisplatin 30 mg/m(2) on day 2
      (PILF). Treatment was repeated every 2 weeks. RESULTS: Of 91 registered patients,
      45 patients were treated with ILF and 45 with PILF. For both arms, 687
      chemotherapy cycles were delivered (median = 7 for ILF and 8 for PILF). Both ILF
      and PILF were generally well tolerated and there was no relevant difference in
      the occurrence of overall grade 3/4 toxic effects between the two arms. Four
      patients died during treatment: one in the ILF and three in the PILF arm. The
      objective response rate was 42% for both arms. There was no significant
      difference in therapeutic efficacy between ILF and PILF with respect to
      progression-free survival (4.8 versus 6.2 months; P = 0.523) and overall survival
      (10.7 versus 10.5 months; P = 0.850). CONCLUSION: Both ILF and PILF are active as
      first-line chemotherapy for AGC. The addition of cisplatin, however, has no clear
      advantage over ILF.

PMID- 18083693
TI  - The off-label use of drugs in oncology: a position paper by the European Society
      for Medical Oncology (ESMO).

PMID- 18083692
TI  - Parental cancer and its effects on adolescents and their families.

PMID- 18083694
TI  - Reversible liver toxicity with adjuvant trastuzumab for localized breast cancer.

PMID- 18083695
TI  - Oncology: a forgotten territory in Africa.

PMID- 18083698
TI  - Markers predicting clinical benefit in breast cancer from microtubule-targeting
      agents.
AB  - Taxanes (e.g. paclitaxel, docetaxel) and epothilones (e.g. ixabepilone) are
      microtubule-targeting agents, which disrupt cellular processes and induce
      apoptosis. Although their mechanisms of action are similar, clinical data in
      breast cancer patients support at least partial non-cross resistance between the
      classes, and even between individual compounds. Several biomarkers might
      contribute to the identification of patient groups likely to derive benefit from
      one class of microtubule-targeting agent or even one agent. Overexpression of P
      glycoprotein is associated with resistance to taxanes, but not ixabepilone, in
      vitro; its role in vivo remains unclear. Mutations in beta-tubulin linked to
      resistance to taxanes but not epothilones are observed in vitro; somatic
      mutations of beta-tubulin appear rare clinically. Overexpression of the betaIII
      tubulin isoform is associated with taxane resistance in cell lines; some clinical
      studies support a relationship between poor response to taxanes and
      overexpression of betaIII-tubulin. BetaIII-tubulin overexpression seems not to
      affect sensitivity to ixabepilone. Estrogen receptor negativity, low expression
      of microtubule-associated protein tau, and perhaps HER2 amplification may define
      a subset of patients with higher than average sensitivity to paclitaxel. Large
      scale pharmacogenomic analysis has identified molecular markers potentially
      capable of distinguishing patients with differential sensitivity to paclitaxel
      and ixabepilone. These markers require validation in clinical trials.

PMID- 18083699
TI  - Adjuvant chemotherapy--yes or no? Prognostic markers in early breast cancer.
AB  - The question of whether to offer adjuvant chemotherapy to patients with early
      stage breast cancer continues to challenge clinicians on a daily basis. Many
      patients with node-negative or low-risk breast cancer could be spared the trauma
      of receiving chemotherapy, but more reliable prognostic markers are still needed
      to aid our therapy decision making. Gene expression profiling is a welcome
      product of the 'omic' era and several multi-gene expression panels ('signatures')
      have now been developed that show promise in predicting which breast cancer
      patients are likely to develop metastatic disease if adjuvant chemotherapy is not
      administered. The value of gene expression profiling as a prognostic tool in
      clinical practice is currently being appraised more fully in two large,
      prospective, randomised studies--TAILORx and MINDACT. These studies should
      provide level I evidence of the prognostic power of gene expression profiling and
      will hopefully allow us to one day quantify risk of progression in the individual
      patient and tailor treatment accordingly. Genetic profiling of circulating tumour
      cells and micrometastases should further enhance our understanding of breast
      cancer biology and allow us to personalise therapy based on functional maps of
      critical tumour pathways. Close collaboration between clinicians and scientists
      will be essential to achieve this goal.

PMID- 18083700
TI  - New strategies to identify molecular markers predicting chemotherapy activity and
      toxicity in breast cancer.
AB  - Despite significant improvements in the treatment and outcomes of early-stage
      breast cancer, the quest continues to find biological and molecular markers that
      would enable earlier diagnosis or better prediction of treatment efficacy and
      toxicity. Metabolomics--the latest and one of the most exciting of the 'omic'
      sciences--has shown early promise as a non-invasive diagnostic aid in ovarian
      cancer, and may allow the detection of subtle metabolic changes that could have
      diagnostic, prognostic or predictive value in breast cancer. Routine monitoring
      of circulating tumour cells (CTCs) has also been advocated as a novel means of
      detecting breast cancer progression earlier, and identifying alterations in
      tumour cells that might signal the need for therapy changes. Ongoing studies
      should help to answer important questions relating to the use of metabolomics and
      CTC evaluation as new strategies to monitor cancer progression and identify
      markers of chemotherapy activity and toxicity.

PMID- 18083701
TI  - ANIBAL, stable isotope-based quantitative proteomics by aniline and benzoic acid
      labeling of amino and carboxylic groups.
AB  - Identification and relative quantification of hundreds to thousands of proteins
      within complex biological samples have become realistic with the emergence of
      stable isotope labeling in combination with high throughput mass spectrometry.
      However, all current chemical approaches target a single amino acid functionality
      (most often lysine or cysteine) despite the fact that addressing two or more
      amino acid side chains would drastically increase quantifiable information as
      shown by in silico analysis in this study. Although the combination of existing
      approaches, e.g. ICAT with isotope-coded protein labeling, is analytically
      feasible, it implies high costs, and the combined application of two different
      chemistries (kits) may not be straightforward. Therefore, we describe here the
      development and validation of a new stable isotope-based quantitative proteomics
      approach, termed aniline benzoic acid labeling (ANIBAL), using a twin chemistry
      approach targeting two frequent amino acid functionalities, the carboxylic and
      amino groups. Two simple and inexpensive reagents, aniline and benzoic acid, in
      their (12)C and (13)C form with convenient mass peak spacing (6 Da) and without
      chromatographic discrimination or modification in fragmentation behavior, are
      used to modify carboxylic and amino groups at the protein level, resulting in an
      identical peptide bond-linked benzoyl modification for both reactions. The ANIBAL
      chemistry is simple and straightforward and is the first method that uses a (13)C
      reagent for a general stable isotope labeling approach of carboxylic groups. In
      silico as well as in vitro analyses clearly revealed the increase in available
      quantifiable information using such a twin approach. ANIBAL was validated by
      means of model peptides and proteins with regard to the quality of the chemistry
      as well as the ionization behavior of the derivatized peptides. A milk fraction
      was used for dynamic range assessment of protein quantification, and a bacterial
      lysate was used for the evaluation of relative protein quantification in a
      complex sample in two different biological states.

PMID- 18083702
TI  - Contrasting the efficacy of selection on the X and autosomes in Drosophila.
AB  - To investigate the relative efficacy of both positive and purifying natural
      selection on the X chromosome and the autosomes in Drosophila, we compared rates
      and patterns of molecular evolution between these chromosome sets using the newly
      available alignments of orthologous genes from 12 species. Parameters that may
      influence the relative X versus autosomal substitution rates include the relative
      effective population sizes, the male and female germline mutation rates, the
      distribution of allelic effects on fitness, and the degree of dominance of novel
      mutations. Our analysis reveals that codon usage bias is consistently greater for
      X-linked genes, suggesting that purifying selection consistently has greater
      efficacy on the X chromosome than on the autosomes across the Drosophila
      phylogeny. However, our results are less consistent with respect to the efficacy
      of positive selection, with only some lineages showing a higher substitution rate
      on the X chromosome. This suggests that either the distribution of selective
      effects of mutations or other relevant parameters are sufficiently variable
      across species to tip the balance in different ways in individual lineages. These
      data suggest that rates of substitution are not solely governed by adaptive
      evolution. This genome-wide analysis provides a clear picture that the efficacy
      of selection varies intragenomically and that this effect is markedly more
      consistent across the phylogeny in the case of purifying selection. Our results
      also suggest that simple models that predict systematic differences in rates of
      evolution between the X and the autosomes can only be made to be compatible with
      these Drosophila data if the relevant population genetic parameters that drive
      substitution rates differ among species and chromosomal contexts.

PMID- 18083703
TI  - Self-rated mental health, school adjustment, and substance use in hard-of-hearing
      adolescents.
AB  - This survey, "Life and Health-Young People 2005," included all 15/16-year-old
      adolescents in mainstream schools in the county of Orebro, Sweden. Just students
      with a slight/mild or moderate hearing loss were included. There were 56 (1.9%)
      "hard-of-hearing (HH) students with multiple disabilities," 93 (3.1%) students
      who were "just HH," 282 (9.7%) students with some "other disability than HH," and
      2,488 (85.2%) students with "no disability." "HH with multiple disabilities"
      reported considerably higher scores for mental symptoms, substance use, and
      school problems than the "no disability" group. Those with "just HH" and those
      with "other disability than HH" had more mental symptoms and school problems than
      the "no disability" group but no significant differences in substance use. In
      conclusion, the combination of a hearing loss and some other disability strongly
      increases the risk for mental symptoms, school problems, and substance use. This
      group, thus, is an important target for preventive measures.

PMID- 18083704
TI  - Generation and characterization of transgenic mice with the full-length human DMD
      gene.
AB  - We report the generation of mice with an intact and functional copy of the 2.3
      megabase human dystrophin gene (hDMD), the largest functional stretch of human
      DNA thus far integrated into a mouse chromosome. Yeast spheroplasts containing an
      artificial chromosome with the full-length hDMD gene were fused with mouse
      embryonic stem cells and were subsequently injected into mouse blastocysts to
      produce transgenic hDMD mice. Human-specific PCR, Southern blotting, and
      fluorescent in situ hybridization techniques demonstrated the intactness and
      stable chromosomal integration of the hDMD gene on mouse chromosome 5. Expression
      of the transgene was confirmed by RT-PCR and Western blotting. The tissue
      specific expression pattern of the different DMD transcripts was maintained.
      However, the human Dp427p and Dp427m transcripts were expressed at 2-fold higher
      levels and human Dp427c and Dp260 transcripts were expressed at 2- and 4-fold
      lower levels than their endogenous counterparts. Ultimate functional proof of the
      hDMD transgene was obtained by crossing of hDMD mice with dystrophin-deficient
      mdx mice and dystrophin and utrophin-deficient mdx x Utrn-/- mice. The hDMD
      transgene rescued the lethal dystrophic phenotype of the mdx x Utrn-/- mice. All
      signs of muscular dystrophy disappeared in the rescued mice, as demonstrated by
      histological staining of muscle sections and gene expression profiling
      experiments. Currently, hDMD mice are extensively used for preclinical testing of
      sequence-specific therapeutics for the treatment of Duchenne muscular dystrophy.
      In addition, the hDMD mouse can be used to study the influence of the genomic
      context on deletion and recombination frequencies, genome stability, and gene
      expression regulation.

PMID- 18083705
TI  - Specific citrullination causes assembly of a globular S100A3 homotetramer: a
      putative Ca2+ modulator matures human hair cuticle.
AB  - S100A3 is a unique member of the Ca2+-binding S100 protein family with the
      highest cysteine content and affinity for Zn2+. This protein is highly expressed
      in the differentiating cuticular cells within the hair follicle and organized
      into mature hair cuticles. Previous studies suggest a close association of S100A3
      with epithelial differentiation, leading to hair shaft formation, but its
      molecular function is still unknown. By two-dimensional PAGE-Western blot
      analyses using a modified citrulline antibody, we discovered that more than half
      of the arginine residues of native S100A3 are progressively converted to
      citrullines by Ca2+-dependent peptidylarginine deiminases. Confocal
      immunofluorescent microscopy showed that the cytoplasmic S100A3 within the
      cuticular layer is mostly co-localized with the type III isoform of
      peptidylarginine deiminase (PAD3) but not with PAD1. Recombinant PAD1 and PAD2
      are capable of converting all 4 arginines in recombinant S100A3, whereas PAD3
      specifically converts only Arg-51 into citrulline. Gel filtration analyses showed
      that either enzymatic conversion of Arg-51 in S100A3 to citrulline or its
      mutational substitution with alanine (R51A) promotes a homotetramer assembly.
      Fluorescent titration of R51A suggested that its potential Ca2+ binding property
      increased during tetramerization. A prototype structural model of the globular
      Ca2+-bound S100A3 tetramer with citrulline residues is presented. High
      concentrations of S100A3 homotetramer might provide the millimolar level of Ca2+
      required for hair cuticular barrier formation.

PMID- 18083706
TI  - Activation of CXCR4 triggers ubiquitination and down-regulation of major
      histocompatibility complex class I (MHC-I) on epithelioid carcinoma HeLa cells.
AB  - Many cancer cells display down-regulated major histocompatibility complex (MHC)
      class I antigen (MHC-I), which seems to enable them to evade immune surveillance,
      whereas the underlying mechanisms remain incompletely understood. Here, we
      demonstrate that ligand (CXCL12) stimulation of CXCR4, a major chemokine receptor
      expressed in many malignant cancer cells, induced MHC-I heavy chain down
      regulation from the cell surface of the human epithelioid carcinoma HeLa cells,
      the human U251 and U87 glioblastoma cells, the human MDA-MD 231 breast cancer
      cells, and the human SK-N-BE (2) neuroblastoma cells. Activation of CXCR4 also
      induced MHC-I down-regulation in human peripheral blood mononuclear cells. The
      internalized MHC-I heavy chain molecules were partially co-localized with Rab7, a
      later endosomal marker. Activation of CXCR4 induced ubiquitination of MHC-I heavy
      chain, and mutation of the C-terminal two lysine residues (Lys-332, Lys-337) on
      one of the MHC-I alleles, HLA.B7, blocked CXCR4-evoked ubiquitination and down
      regulation of HLA.B7. Moreover, purified GST-conjugated CXCR4 C terminus directly
      associated with the purified His-tagged beta2-microglobulin (beta2M), and MHC-I
      heavy chain was co-immunoprecipitated with CXCR4 in a beta2M-dependent manner.
      This interaction appears to be critical for CXCR4-evoked down-regulation of MHC-I
      heavy chain as evidenced by the data that MHC-I heavy chain down-regulation was
      inhibited by either truncation of the CXCR4 C terminus or knockdown of beta2M.
      All together, these findings shed new light on the role of CXCR4 in tumor evasion
      of immune surveillance via inducing MHC-I down-regulation from the cell surface.

PMID- 18083707
TI  - Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel
      conformational switch.
AB  - The p62 protein functions as a scaffold in signaling pathways that lead to
      activation of NF-kappaB and is an important regulator of osteoclastogenesis.
      Mutations affecting the receptor activator of NF-kappaB signaling axis can result
      in human skeletal disorders, including those identified in the C-terminal
      ubiquitin-associated (UBA) domain of p62 in patients with Paget disease of bone.
      These observations suggest that the disease may involve a common mechanism
      related to alterations in the ubiquitin-binding properties of p62. The structural
      basis for ubiquitin recognition by the UBA domain of p62 has been investigated
      using NMR and reveals a novel binding mechanism involving a slow exchange
      structural reorganization of the UBA domain to a "bound" non-canonical UBA
      conformation that is not significantly populated in the absence of ubiquitin. The
      repacking of the three-helix bundle generates a binding surface localized around
      the conserved Xaa-Gly-Phe-Xaa loop that appears to optimize both hydrophobic and
      electrostatic surface complementarity with ubiquitin. NMR titration analysis
      shows that the p62-UBA binds to Lys 48-linked di-ubiquitin with approximately 4
      fold lower affinity than to mono-ubiquitin, suggesting preferential binding of
      the p62-UBA to single ubiquitin units, consistent with the apparent in vivo
      preference of the p62 protein for Lys 63-linked polyubiquitin chains (which adopt
      a more open and extended structure). The conformational switch observed on
      binding may represent a novel mechanism that underlies specificity in regulating
      signalinduced protein recognition events.

PMID- 18083709
TI  - LysM domains from Pteris ryukyuensis chitinase-A: a stability study and
      characterization of the chitin-binding site.
AB  - The LysM domain probably binds peptidoglycans, but how it does so has yet to be
      described. For this report, we measured the thermal stabilities of recombinant
      LysM domains derived from Pteris ryukyuensis chitinase-A (PrChi-A) and monitored
      their binding to N-acetylglucosamine oligomers ((GlcNAc)n) using differential
      scanning calorimetry, isothermal titration calorimetry, and NMR spectroscopy. We
      thereby characterized certain of the domains' functional and structural features.
      We observed that the domains are very resistant to thermal denaturation and that
      this resistance depends on the presence of disulfide bonds. We also show that the
      stoichiometry of (GlcNAc)n/LysM domain binding is 1:1. (GlcNAc)5 titration
      experiments, monitored by NMR spectroscopy, allowed us to identify the domain
      residues that are critical for (GlcNAc)5 binding. The binding site is a shallow
      groove formed by the N-terminal part of helix 1, the loop between strand 1 and
      helix 1, the C-terminal part of helix 2, and the loop between helix 2 and strand
      2. Furthermore, mutagenesis experiments reiterate the critical involvement of
      Tyr72 in (GlcNAc)n/LysM domain binding. Ours is the first report describing the
      physical structure of a LysM oligosaccharide-binding site based on experimental
      data.

PMID- 18083710
TI  - Dual roles of the central domain of colicin D tRNase in TonB-mediated import and
      in immunity.
AB  - Colicin D import into Escherichia coli requires an interaction via its TonB box
      with the energy transducer TonB. Colicin D cytotoxicity is inhibited by specific
      tonB mutations, but it is restored by suppressor mutations in the TonB box. Here
      we report that there is a second site of interaction between TonB and colicin D,
      which is dependent upon a 45-amino acid region, within the uncharacterized
      central domain of colicin D. In addition, the 8th amino acids of colicin D (a
      glycine) and colicin B (a valine), adjacent to their TonB boxes, are also
      required for TonB recognition, suggesting that high affinity complex formation
      involves multiple interactions between these colicins and TonB. The central
      domain also contributes to the formation of the immunity complex, as well as
      being essential for uptake and thus killing. Colicin D is normally secreted in
      association with the immunity protein, and this complex involves the following
      two interactions: a major interaction with the C-terminal tRNase domain and a
      second interaction involving the central domain of colicin D and, most probably,
      the alpha4 helix of ImmD, which is on the opposite side of ImmD compared with the
      major interface. In contrast, formation of the immunity complex with the
      processed cytotoxic domain, the form expected to be found in the cytoplasm after
      colicin D uptake, requires only the major interaction. Klebicin D has, like
      colicin D, a ribonuclease activity toward tRNAArg and a central domain, which can
      form a complex with ImmD but which does not function in TonB-mediated transport.

PMID- 18083708
TI  - Activation of cytosolic phospholipase A2alpha in resident peritoneal macrophages
      by Listeria monocytogenes involves listeriolysin O and TLR2.
AB  - Eicosanoid production by macrophages is an early response to microbial infection
      that promotes acute inflammation. The intracellular pathogen Listeria
      monocytogenes stimulates arachidonic acid release and eicosanoid production from
      resident mouse peritoneal macrophages through activation of group IVA cytosolic
      phospholipase A2 (cPLA2alpha). The ability of wild type L. monocytogenes (WTLM)
      to stimulate arachidonic acid release is partially dependent on the virulence
      factor listeriolysin O; however, WTLM and L. monocytogenes lacking listeriolysin
      O (DeltahlyLM) induce similar levels of cyclooxygenase 2. Arachidonic acid
      release requires activation of MAPKs by WTLM and DeltahlyLM. The attenuated
      release of arachidonic acid that is observed in TLR2-/- and MyD88-/- macrophages
      infected with WTLM and DeltahlyLM correlates with diminished MAPK activation.
      WTLM but not DeltahlyLM increases intracellular calcium, which is implicated in
      regulation of cPLA2alpha. Prostaglandin E2, prostaglandin I2, and leukotriene C4
      are produced by cPLA2alpha+/+ but not cPLA2alpha-/- macrophages in response to
      WTLM and DeltahlyLM. Tumor necrosis factor (TNF)-alpha production is
      significantly lower in cPLA2alpha+/+ than in cPLA2alpha-/- macrophages infected
      with WTLM and DeltahlyLM. Treatment of infected cPLA2alpha+/+ macrophages with
      the cyclooxygenase inhibitor indomethacin increases TNFalpha production to the
      level produced by cPLA2alpha-/- macrophages implicating prostaglandins in
      TNFalpha down-regulation. Therefore activation of cPLA2alpha in macrophages may
      impact immune responses to L. monocytogenes.

PMID- 18083711
TI  - The docking interaction of caspase-9 with ERK2 provides a mechanism for the
      selective inhibitory phosphorylation of caspase-9 at threonine 125.
AB  - Caspase-9 plays a critical role in the initiation of apoptosis by the
      mitochondrial pathway. Activation of caspase-9 is inhibited by phosphorylation at
      Thr(125) by ERK1/2 MAPKs in response to growth factors. Here, we show that
      phosphorylation of this site is specific for these classical MAPKs and is not
      strongly induced when JNK and p38alpha/beta MAPKs are activated by anisomycin. By
      deletion and mutagenic analysis, we identify domains in caspase-9 and ERK2 that
      mediate their interaction. Binding of ERK2 to caspase-9 and subsequent
      phosphorylation of caspase-9 requires a basic docking domain (D domain) in the N
      terminal prodomain of the caspase. Mutational analysis of ERK2 reveals a
      (157)TTCD(160) motif required for recognition of caspase-9 that acts
      independently of the putative common docking domain. Molecular modeling supports
      the conclusion that Arg(10) in the D domain of caspase-9 interacts with Asp(160)
      in the TTCD motif of ERK2. Differences in the TTCD motif in other MAPK family
      members could account for the selective recognition of caspase-9 by ERK1/2. This
      selectivity may be important for the antiapoptotic role of classical MAPKs in
      contrast to the proapoptotic roles of stress-activated MAPKs.

PMID- 18083712
TI  - EP2 and EP4 receptors regulate aromatase expression in human adipocytes and
      breast cancer cells. Evidence of a BRCA1 and p300 exchange.
AB  - Cytochrome P450 aromatase (aromatase), a product of the CYP19 gene, catalyzes the
      synthesis of estrogens from androgens. Because aromatase-dependent estrogen
      biosynthesis has been linked to hormone-dependent breast carcinogenesis, it is
      important to elucidate the mechanisms that regulate CYP19 gene expression. The
      main objective of this study was to identify the receptors (EP) for prostaglandin
      E(2) (PGE(2)) that mediate the induction of CYP19 transcription in human
      adipocytes and breast cancer cells. Treatment with PGE(2) induced aromatase, an
      effect that was mimicked by either EP(2) or EP(4) agonists. Antagonists of EP(2)
      or EP(4) or small interference RNA-mediated down-regulation of these receptors
      suppressed PGE(2)-mediated induction of aromatase. PGE(2) via EP(2) and EP(4)
      stimulated the cAMP-->protein kinase A pathway resulting in enhanced interaction
      between P-CREB, p300, and the aromatase promoter I.3/II. Overexpressing a mutant
      form of p300 that lacks histone acetyltransferase activity suppressed PGE(2)
      mediated induction of aromatase promoter activity. PGE(2) via EP(2) and EP(4)
      also caused a reduction in both the amounts of BRCA1 and the interaction between
      BRCA1 and the aromatase promoter I.3/II. Activation of the aromatase promoter by
      PGE(2) was suppressed by overexpressing wild-type BRCA1. Silencing of EP(2) or
      EP(4) also blocked PGE(2)-mediated induction of the progesterone receptor, a
      prototypic estrogen-response gene. In a mouse model, overexpressing COX-2 in the
      mammary gland, a known inducer of PGE(2) synthesis, led to increased aromatase
      mRNA and activity and reduced amounts of BRCA1; these effects were reversed by
      knocking out EP(2). Taken together, these results suggest that PGE(2) via EP(2)
      and EP(4) activates the cAMP-->PKA-->CREB pathway leading to enhanced CYP19
      transcription and increased aromatase activity. Reciprocal changes in the
      interaction between BRCA1, p300, and the aromatase promoter I.3/II contributed to
      the inductive effects of PGE(2).

PMID- 18083713
TI  - Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice:
      two possible routes for menaquinone-4 accumulation in cerebra of mice.
AB  - There are two forms of naturally occurring vitamin K, phylloquinone and the
      menaquinones. Phylloquinone (vitamin K(1)) is a major type (>90%) of dietary
      vitamin K, but its concentrations in animal tissues are remarkably low compared
      with those of the menaquinones, especially menaquinone-4 (vitamin K(2)), the
      major form (>90%) of vitamin K in tissues. Despite this great difference, the
      origin of tissue menaquinone-4 has yet to be exclusively defined. It is
      postulated that phylloquinone is converted into menaquinone-4 and accumulates in
      extrahepatic tissues. To clarify this, phylloquinone with a deuterium-labeled 2
      methyl-1,4-naphthoquinone ring was given orally to mice, and cerebra were
      collected for D NMR and liquid chromatography-tandem mass spectrometry analyses.
      We identified the labeled menaquinone-4 that was converted from the given
      phylloquinone, and this conversion occurred following an oral or enteral
      administration, but not parenteral or intracerebroventricular administration. By
      the oral route, the phylloquinone with the deuterium-labeled side chain in
      addition to the labeled 2-methyl-1,4-naphthoquinone was clearly converted into a
      labeled menaquinone-4 with a non-deuterium-labeled side chain, implying that
      phylloquinone was converted into menaquinone-4 via integral side-chain removal.
      The conversion also occurred in cerebral slice cultures and primary cultures.
      Deuterium-labeled menadione was consistently converted into the labeled
      menaquinone-4 with all of the administration routes and the culture conditions
      tested. Our results suggest that cerebral menaquinone-4 originates from
      phylloquinone intake and that there are two routes of accumulation, one is the
      release of menadione from phylloquinone in the intestine followed by the
      prenylation of menadione into menaquinone-4 in tissues, and another is cleavage
      and prenylation within the cerebrum.

PMID- 18083714
TI  - Cross-sectional association between perceived discrimination and hypertension in
      African-American men and women: the Pitt County Study.
AB  - Few studies have examined the impact of the frequency of discrimination on
      hypertension risk. The authors assessed the cross-sectional associations between
      frequency of perceived racial and nonracial discrimination and hypertension among
      1,110 middle-aged African-American men (n = 393) and women (n = 717)
      participating in the 2001 follow-up of the Pitt County Study (Pitt County, North
      Carolina). Odds ratios were estimated using gender-specific unconditional
      weighted logistic regression with adjustment for relevant confounders and the
      frequency of discrimination. More than half of the men (57%) and women (55%) were
      hypertensive. The prevalences of perceived racial discrimination, nonracial
      discrimination, and no discrimination were 57%, 29%, and 13%, respectively, in
      men and 42%, 43%, and 15%, respectively, in women. Women recounting frequent
      nonracial discrimination versus those reporting no exposure to discrimination had
      the highest odds of hypertension (adjusted odds ratio = 2.34, 95% confidence
      interval: 1.09, 5.02). A nonsignificant inverse odds ratio was evident in men who
      perceived frequent exposure to racial or nonracial discrimination in comparison
      with no exposure. A similar association was observed for women reporting
      perceived racial discrimination. These results indicate that the type and
      frequency of discrimination perceived by African-American men and women may
      differentially affect their risk of hypertension.

PMID- 18083716
TI  - Does germination success differ with respect to seed mass and germination season?
      Experimental testing of plant functional trait responses to grassland management.
AB  - BACKGROUND AND AIMS: Plant functional trait responses to processes such as
      grassland management have been analysed frequently; however, the scaling-up from
      individual traits to the outcomes of vegetation dynamics has seldom been tested.
      In this experiment, germination success was studied with respect to the
      relationships between grassland management (mowing and grazing), as well as
      abandonment, and two traits that are relevant for seedling recruitment: seed mass
      and germination season. On the basis of discussions in the literature and
      indirect trait analyses in our previous studies, the following hypotheses are
      proposed: (1) with respect to seed mass, mowing and grazing favour the
      germination of small seeds, whereas after abandonment the germination success of
      larger seeds is higher; and (2) with respect to germination season, mowing and
      grazing favour autumn-germinating seeds, whereas succession promotes spring
      germinating seeds. METHODS: The germination experiment took place in a semi
      natural, dry grassland in north-east Germany. Seeds of eight herbaceous species
      that differ with respect to seed mass and germination season were sown in mown,
      grazed and abandoned plots. Germination success was documented during the
      following year. KEY RESULTS AND CONCLUSIONS: Contrary to the hypothesis,
      germination of small seeds was not promoted by mowing or grazing and they
      germinated relatively more often than expected in the abandoned plots. A
      relationship between abandonment and gaps of bare soil below the vegetation cover
      that favour germination of small seeds was likely, but could not be proved
      statistically. It is possible that the small seeds suffered less from predation.
      Mowing favoured autumn germination, which could be explained by the removal of
      biomass in late summer. Contrary to our expectation, there was relatively more
      spring germination after grazing than after mowing, yet vegetation height was
      smallest in spring. Generally, germination season was found to be related to the
      temporal occurrence of favourable light conditions.

PMID- 18083717
TI  - Incorporating gene networks into statistical tests for genomic data via a
      spatially correlated mixture model.
AB  - MOTIVATION: It is a common task in genomic studies to identify a subset of the
      genes satisfying certain conditions, such as differentially expressed genes or
      regulatory target genes of a transcription factor (TF). This can be formulated as
      a statistical hypothesis testing problem. Most existing approaches treat the
      genes as having an identical and independent distribution a priori, testing each
      gene independently or testing some subsets of the genes one by one. On the other
      hand, it is known that the genes work coordinately as dictated by gene networks.
      Treating genes equally and independently ignores the important information
      contained in gene networks, leading to inefficient analysis and reduced power.
      RESULTS: We propose incorporating gene network information into statistical
      analysis of genomic data. Specifically, rather than treating the genes equally
      and independently a priori in a standard mixture model, we assume that gene
      specific prior probabilities are correlated as induced by a gene network: while
      the genes are allowed to have different prior probabilities, those neighboring
      ones in the network have similar prior probabilities, reflecting their shared
      biological functions. We applied the two approaches to a real ChIP-chip dataset
      (and simulated data) to identify the transcriptional target genes of TF GCN4. The
      new method was found to be more powerful in discovering the target genes.

PMID- 18083718
TI  - Efficient peptide-MHC-I binding prediction for alleles with few known binders.
AB  - MOTIVATION: In silico methods for the prediction of antigenic peptides binding to
      MHC class I molecules play an increasingly important role in the identification
      of T-cell epitopes. Statistical and machine learning methods in particular are
      widely used to score candidate binders based on their similarity with known
      binders and non-binders. The genes coding for the MHC molecules, however, are
      highly polymorphic, and statistical methods have difficulties building models for
      alleles with few known binders. In this context, recent work has demonstrated the
      utility of leveraging information across alleles to improve the performance of
      the prediction. RESULTS: We design a support vector machine algorithm that is
      able to learn peptide-MHC-I binding models for many alleles simultaneously, by
      sharing binding information across alleles. The sharing of information is
      controlled by a user-defined measure of similarity between alleles. We show that
      this similarity can be defined in terms of supertypes, or more directly by
      comparing key residues known to play a role in the peptide-MHC binding. We
      illustrate the potential of this approach on various benchmark experiments where
      it outperforms other state-of-the-art methods. AVAILABILITY: The method is
      implemented on a web server: http://cbio.ensmp.fr/kiss. All data and codes are
      freely and publicly available from the authors.

PMID- 18083719
TI  - Use of faecal excretion function for quick estimation of initial and existing
      lung burden for occupational exposure control due to 239Pu for S-class of intake.
AB  - Two functions namely initial lung deposition and lung retention per unit faecal
      excretion rate are constructed primarily based on the excretion pattern of four
      subjects exposed to (239)Pu. In the absence of initial clear knowledge about the
      class of compound inhaled, faecal to urine excretion ratio was used to infer the
      type of inhaled class. Trends in the urine and faecal data had suggested that the
      intake was due to mixed class of plutonium compound for each case. With the
      assumption of 1:1 mixture of plutonium M&S class inhaled compound, faecal
      excretion rates for only S-class intake were worked out. Uptake inferred based on
      their urinary data had suggested it to be of similar level within 40% of
      uncertainty for 5 microm particle size distribution. Data, all the four cases,
      were pooled for analysis citing the similar level of intake, particle size
      distribution, nature and pattern of work. The function obtained was tested for S
      class lung retention and faecal excretion rate value. These functions are handy
      tool for estimating initial lung burden and lung retention value for low level of
      S-class plutonium intake based on subject faecal analysis data.

PMID- 18083720
TI  - Maximum likelihood estimates of mean and variance of occupation radiation doses
      subjected to minimum detection levels.
AB  - Data collection and its analysis in the field of nuclear safety is an important
      task in the sense that it powers the improvement of safety as well as reliability
      of the plant. Thus, occupational exposure data analysis is presented to measure
      the safety or reliability of radiation protection of a given facility. It also is
      required as a basic input in making decisions on radiation protection regulations
      and recommendations. A common practice in radiation protection is to record a
      zero for observation below minimum detection limit (MDL) doses, which leads to an
      underestimation of true doses and overestimation of the dose-response
      relationship. Exposure data (both external and internal) are collected by
      monitoring each individual and this kind of monitoring generally is graded as low
      level monitoring. So, in such low-level monitoring, the occurrence of exposure
      below MDL invites statistical complications for estimating mean and variance
      because the data are generally censored, i.e observations below MDL are marked.
      In Type I censoring, the point of censoring (e.g. the detection limit) is 'fixed'
      a priori for all observations and the number of the censored observations varies.
      In Type II censoring, the number of censored observations is fixed a priori, and
      the point of censoring vary. The methodology generally followed in estimating
      mean and variance with these censored data was the replacement of missing dose by
      half the MDL. In this paper, authors have used the maximum likelihood estimation
      (MLE) approach for the estimation of mean and standard deviation. A computer code
      BDLCENSOR has been developed in which all these MLE-based advanced algorithms are
      implemented. In addition to the MLE-based method, an expectation maximisation
      algorithm has also been implemented. The code is written using Visual BASIC 6.0.
      The paper describes the details of the algorithms adopted for handling such
      censored data to estimate bias free mean and standard deviation.

PMID- 18083715
TI  - Molecular mechanisms of the conjugated alpha,beta-unsaturated carbonyl
      derivatives: relevance to neurotoxicity and neurodegenerative diseases.
AB  - Conjugated alpha,beta-unsaturated carbonyl derivatives such acrylamide, acrolein,
      and 4-hydroxy-2-nonenal (HNE) are members of a large class of chemicals known as
      the type-2 alkenes. Human exposure through diet, occupation, and pollution is
      pervasive and has been linked to toxicity in most major organs. Evidence suggests
      that these soft electrophiles produce toxicity by a common mechanism involving
      the formation of Michael-type adducts with nucleophilic sulfhydryl groups. In
      this commentary, the adduct chemistry of the alpha,beta-unsaturated carbonyls and
      possible protein targets will be reviewed. We also consider how differences in
      electrophilic reactivity among the type-2 alkenes impact corresponding
      toxicokinetics and toxicological expression. Whereas these concepts have
      mechanistic implications for the general toxicity of type-2 alkenes, this
      commentary will focus on the ability of these chemicals to produce presynaptic
      damage via protein adduct formation. Given the ubiquitous environmental presence
      of the conjugated alkenes, discussions of molecular mechanisms and possible
      neurotoxicological risks could be important. Understanding the neurotoxicodynamic
      of the type-2 alkenes might also provide mechanistic insight into
      neurodegenerative conditions where neuronal oxidative stress and presynaptic
      dysfunction are presumed initiating events. This is particularly germane to a
      recent proposal that lipid peroxidation and the subsequent liberation of acrolein
      and HNE in oxidatively stressed neurons mediate synaptotoxicity in brains of
      Alzheimer's disease patients. This endogenous neuropathogenic process could be
      accelerated by environmental type-2 alkene exposure because common nerve terminal
      proteins are targeted by alpha,beta-unsaturated carbonyl derivatives. Thus, the
      protein adduct chemistry of the conjugated type-2 alkenes offers a mechanistic
      explanation for the environmental toxicity induced by these chemicals and might
      provide insight into the pathogenesis of certain human neurodegenerative
      diseases.

PMID- 18083721
TI  - Exposure to radon in dwellings in the Sharri community, Kosovo.
AB  - Indoor air radon concentration was measured by exposing etched track detectors in
      the sleeping and living rooms of 18 houses in 6 villages of the Sharri community
      in Kosovo. Values ranged from 24 to 209 Bq m(-3), with only one exceeding 200 Bq
      m(-3), with a geometric mean and geometric standard deviation of 95.4 Bq m(-3)
      and 1.6, respectively. On the basis of the assumption that the spring radon
      concentrations obtained in this survey represent the yearly average, annual
      effective doses of residents were calculated; they range from 0.89 to 4.7 mSv y(
      1), with the geometric mean and geometric standard deviation of 1.5 mSv y(-1) and
      2.2, respectively. No mitigation measures are planned to be undertaken.

PMID- 18083722
TI  - Three lectures on case-control genetic association analysis.
AB  - The purpose of this review is to focus on the three most important themes in
      genetic association studies using randomly selected patients (case, affected) and
      normal samples (control, unaffected), so that students and researchers alike who
      are new to this field may quickly grasp the key issues and command basic analysis
      methods. These three themes are: elementary categorical analysis; disease
      mutation as an unobserved entity; and the importance of homogeneity in genetic
      association analysis.

PMID- 18083723
TI  - Detecting chronic kidney disease in older people; what are the implications?
AB  - BACKGROUND: national policy is focused on early identification, referral and
      management of chronic kidney disease (CKD) to prevent both progression to
      endstage renal failure and cardiovascular disease. However, the significance of
      identifying CKD in older people is unclear. OBJECTIVE: to determine the frequency
      of CKD in older people using estimated glomerular filtration rate (eGFR), and its
      associations with morbidity and functional measures. DESIGN: observational cross
      sectional analysis of baseline data from a large cluster randomised trial of
      health and social assessment of older people in the community. SETTING: included
      53 general practices in Great Britain. SUBJECTS: subjects were people aged 75 and
      over, living in the community participating in the trial arm where systematic
      blood testing was undertaken. METHODS: the response rate for participation at
      baseline assessment of those eligible was 73% (15,536/20,934), of whom 13,109
      (86%) participants had a serum creatinine measured, and an eGFR derivable using
      the Modification of Diet in Renal Disease formula (MDRD) in ml/min/1.73 m(2). Key
      outcomes were the prevalence of CKD stages and their associations with morbidity
      and functional status. RESULTS: prevalence of CKD was 56.1% (95% CI 55.3-57.0)
      for eGFR < 60, 17.7% for eGFR < 45 (95% CI 17.1-18.4), and 2.7% (95% CI 2.4-2.9)
      for eGFR < 30. It was higher in older ages, females, and those with
      cardiovascular comorbidity and doctor-diagnosed hypertension but not with
      diabetes. The strength of the association with measures of morbidity and
      functional impairment increased as eGFR fell, especially once the eGFR was < 45.
      For example, the odds ratios in males for anaemia for an eGFR < 30, 30-44 and 45
      59 versus reference GFR > 60 were 8.3 (5.1-13.7), 3.0 (2.1-4.2) and 1.2(0.8-1.7)
      respectively; similar figures for partial dependence on activities of daily
      living were 2.2 (1.4-3.3), 1.6 (1.2-2.1) and 1.0 (0.9-1.3) and for lack of
      physical activity 2.20 (1.39-3.48), 1.78 (1.37-2.32) and 1.10 (0.92-1.32).
      CONCLUSIONS: an eGFR < 60 is very common in older people. An eGFR < 45 identifies
      a smaller sub-group of older people with significant comorbidity, impaired
      functional state and a high risk of potentially reversible consequences such as
      anaemia. The benefits of identifying older people with an eGFR > 45 need to be
      determined.

PMID- 18083724
TI  - Educating nursing home staff on fracture prevention: a cluster randomised trial.
AB  - OBJECTIVE: to assess whether specialist osteoporosis nurses delivering training
      to care home staff can reduce fractures and improve the prescription of
      treatments to reduce fractures versus usual care. DESIGN: pragmatic cluster
      randomised controlled trial (RCT) with randomisation at the Primary Care
      Organisation (PCO) level. SETTING: care homes (residential, nursing and EMI)
      across England and Wales within PCOs. PARTICIPANTS: all 300 PCOs in England and
      Wales were invited to take part. Of these, 58 agreed to participate and gained
      ethical approval in time to start the study: 29 clusters were randomised to the
      intervention group and 29 to the control. INTERVENTION: specialist osteoporosis
      nurses undertaking short training sessions with care home staff emphase the
      importance of fracture and fall prevention and train staff on how to identify
      those residents at high risk of fracture. Residents' risk of fracture and falls
      was reported to general practitioners (GPs) of patients along with treatment
      recommendations. OUTCOME MEASURES: primary outcome measures were total fractures
      over the past 12 months and total hip fractures over past the 12 months.
      Secondary outcome measures were total home falls, number of residents sustaining
      a fall, number of residents prescribed bisphosphonates, number of residents
      prescribed calcium and vitamin D and number of residents wearing hip protectors.
      All outcomes were measured at the care home level. RESULTS: of the 230 care homes
      randomised data were collected from 209 of these containing 5,637 residents.
      There were no differences between the groups in the incidence rate ratios (IRRs)
      for total fractures (IRR = 0.94 [0.71, 1.26] P = 0.70) or total hip fractures
      (IRR = 0.86 [0.63, 1.18] P = 0.36). No differences were found between groups for
      home falls or hip protector use. A significant increase in bisphosphonate
      prescription was seen in the intervention group over the control group (IRR =
      1.50 [1.00, 2.24] P = 0.05). Calcium and vitamin D prescription was significantly
      increased in the intervention group over the control group (IRR = 1.64 [1.23,
      2.18] P<0.01). CONCLUSION: the intervention significantly increased the
      prescription of bisphosphonates and calcium/vitamin D, but was not associated
      with a significant effect on the rate of falls or fractures.

PMID- 18083725
TI  - Energy saving processes in huddling emperor penguins: from experiments to theory.
AB  - This paper investigates the energy savings of male emperor penguins Aptenodytes
      forsteri linked to their huddling behaviour, the key factor that allows them to
      assume their incubating task while undergoing a long fast. Drawing on new studies
      by our team, this review examines the energetic benefits accrued from huddling
      and estimates the respective contributions of wind protection, exposure to mild
      ambient temperatures, reduction in cold-exposed body surfaces and body
      temperature adjustments in these energy savings. The metabolic rate of 'loosely
      grouped' birds (restrained in small groups of 5-10 individuals, which are unable
      to huddle effectively) is reduced by 39% compared to metabolic rate of 'isolated'
      birds, with 32% of these energetic benefits due to wind protection. In addition,
      metabolic rate of 'free-ranging' emperors, i.e. able to move freely and to
      huddle, is on average 21% lower than that of 'loosely grouped' birds. Exposure to
      mild ambient temperatures within the groups and reduction in cold-exposed body
      surfaces while huddling, though overestimated, would represent a 38% metabolic
      reduction. About two thirds of metabolic lowering is attributable to the
      reduction in cold-exposed body surfaces and one third to the mild microclimate
      created within the groups. Moreover, body temperature adjustments contribute to
      these energetic benefits: maintaining body temperatures 1 degrees C lower would
      represent a 7-17% reduction in energy expenditure. These processes, linked
      together, explain how huddling emperors save energy and maintain a constant body
      temperature, which ensures a successful incubation in the midst of the austral
      winter.

PMID- 18083726
TI  - Time-variant spectral peak and notch detection in echolocation-call sequences in
      bats.
AB  - Bats are able to recognize and discriminate three-dimensional objects in complete
      darkness by analyzing the echoes of their ultrasonic emissions. Bats typically
      ensonify objects from different aspects to gain an internal representation of the
      three-dimensional object shape. Previous work suggests that, as a result, bats
      rely on the echo-acoustic analysis of spectral peaks and notches. Dependent on
      the aspect of ensonification, this spectral interference pattern changes over
      time in an object-specific manner. The speed with which the bats' auditory system
      can follow time-variant spectral interference patterns is unknown. Here, we
      measured the detection thresholds for temporal variations in the spectral content
      of synthesized echolocation calls in the echolocating bat, Megaderma lyra. In a
      two-alternative, forced-choice procedure, bats were trained to discriminate
      synthesized echolocation-call sequences with time-variant spectral peaks or
      notches from echolocation-call sequences with invariant peaks or notches.
      Detection thresholds of the spectral modulations were measured by varying the
      modulation depth of the time-variant echolocation-call sequences for modulation
      rates ranging from 2 to 16 Hz. Both for spectral peaks and notches, modulation
      detection thresholds were at a modulation depth of approximately 11% of the
      centre frequency. Interestingly, thresholds were relatively independent of
      modulation rate. Acknowledging reservations about direct comparisons of active
      acoustic and passive-acoustic auditory processing, the effectual sensitivity and
      modulation-rate independency of the obtained results indicate that the bats are
      well capable of tracking changes in the spectral composition of echoes reflected
      by complex objects from different angles.

PMID- 18083727
TI  - The Drosophila muscle LIM protein, Mlp84B, is essential for cardiac function.
AB  - Muscle LIM protein (MLP) is a cytoskeletal protein located at the Z-disc of
      sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and
      dilated cardiomyopathy. MLP has been proposed to be a key player in the stretch
      sensing response, but the molecular mechanisms underlying its function in normal
      and diseased cardiac muscle have not been established. A Drosophila homolog,
      Mlp84B, displays a similar subcellular localization at the Z-disc of sarcomeres
      throughout development and in the adult, suggesting Drosophila as a model to
      study MLP function. Here we employed genetic ablation and cardiac-specific RNA
      interference (RNAi) knockdown of mlp84B to investigate its role in heart
      function. We found that Mlp84B-deficient or heart-specific RNAi knockdown flies
      exhibit diastolic interval prolongation, heart rhythm abnormalities and a reduced
      lifespan, while showing no obvious structural phenotype. Our data demonstrate
      that Mlp84B is essential for normal cardiac function and establish the Drosophila
      model for the investigation of the mechanisms connecting defective cardiac Z-disc
      components to the development of cardiomyopathy.

PMID- 18083728
TI  - Impaired escape flight ability in butterflies due to low flight muscle ratio
      prior to hibernation.
AB  - For an animal to escape an attacking predator, speed and manoeuvrability are
      likely to be crucial factors. Previous studies on reptiles and birds have
      revealed that gaining weight, due to for instance egg load or lipid accumulation,
      leads to impaired escape ability and possibly increases the risk of being caught
      by predators. Here we tested whether the flight performance of an insect, the
      small tortoiseshell butterfly (Aglais urticae), is affected by variations in body
      mass due to feeding by comparing flight performance parameters between
      individuals that (i) took flight spontaneously or after being subjected to a
      simulated predator attack and (ii) varied in flight muscle ratio (FMR: thorax
      mass/total body mass). The results show that butterflies that were subjected to a
      simulated predator attack flew at higher velocities and straighter than
      butterflies that were allowed to take off spontaneously. Furthermore, our study
      suggests, for the first time, that butterflies may experience impaired escape
      ability after feeding, which directly leads to a decrease in FMR; a reduction
      from 0.5 to 0.3 reduced escape flight velocity by about 37% at 0.5 m from the
      start. Finally, this study shows that FMR affects take-off angle and sinuosity,
      with steeper angles and more turning in butterflies with low FMR.

PMID- 18083729
TI  - Selective mobilization of fatty acids from adipose tissue in migratory birds.
AB  - During times of high energy demand, stored fatty acids are mobilized from
      adipocytes. This mobilization has previously been shown to be a non-random
      process, with more hydrophilic fatty acids being mobilized most readily. The
      objectives of this study were to characterize the relative mobilization of fatty
      acids from adipocytes in two migratory bird species and to investigate possible
      changes in selective fatty acid mobilization associated with the migratory
      period. Captive ruffs (Philomachus pugnax) and white-crowned sparrows
      (Zonotrichia leucophrys) were studied. The sparrows were divided into two
      treatments: 'winter' (photoperiod 8 h:16 h L:D) and 'migrant' (in which migratory
      condition was induced with a photoperiodic manipulation of 8 h:16 h L:D, followed
      by 16 h:8 h L:D). Adipose tissue was removed from ruffs and sparrows and
      incubated for 90 min after stimulation with epinephrine. The proportions of
      individual fatty acid species released into the incubation medium were compared
      with their proportions in the adipocytes to determine relative mobilizations. We
      found that patterns of relative mobilization in ruffs and sparrows are similar to
      those of mammals, with shorter chain lengths and more double bonds leading to
      higher relative mobilization. Seasonal condition in sparrows did not alter this
      pattern. This pattern of relative mobilization from adipocytes seems to be a
      general rule amongst birds and mammals and should be considered before inferring
      functionality about selective retention or mobilization of certain fatty acids.
      The composition of adipose stores in birds may affect migratory performance;
      however, our results indicate that patterns of relative mobilization at the
      adipocytes do not vary with season in migratory birds.

PMID- 18083730
TI  - Development partly determines the aerobic performance of adult deer mice,
      Peromyscus maniculatus.
AB  - Previous studies suggest that genetic factors and acclimation can account for
      differences in aerobic performance (V(O(2)max)) between high and low altitude
      populations of small mammals. However, it remains unclear to what extent
      development at different oxygen partial pressures (P(O(2))) can affect aerobic
      performance during adulthood. Here we compared the effects of development at
      contrasting altitudes versus effects of acclimation during adulthood on
      V(O(2)max). Two groups of deer mice were born and raised for 5 weeks at one of
      two altitudes (340 and 3800 m above sea level). Then, a subset of each group was
      acclimated to the opposite altitude for 8 weeks. We measured V(O(2)max) for each
      individual in hypoxia (P(O(2))=13.5 kPa, 14% O(2) at 3800 m) and normoxia
      (P(O(2))=20.4 kPa, 21% O(2) at 340 m) to control for P(O(2)) effects. At 5 weeks
      of age, high altitude born mice attained significantly higher V(O(2)max) than low
      altitude born mice (37.1% higher in hypoxia and 72.1% higher in normoxia).
      Subsequently, deer mice acclimated for 8 weeks to high altitude had significantly
      higher V(O(2)max) regardless of their birth site (21.0% and 72.9% difference in
      hypoxia and normoxia, respectively). A significant development x acclimation site
      interaction comparing V(O(2)max) in hypoxia and normoxia at 13 weeks of age
      suggests that acclimation effects depend on development altitude. Thus,
      reversible plasticity during adulthood cannot fully compensate for developmental
      effects on aerobic performance. We also found that differences in aerobic
      performance in previous studies may have been underestimated if animals from
      contrasting altitudes were measured at different P(O(2)).

PMID- 18083731
TI  - Differential actions of diuretic factors on the Malpighian tubules of Rhodnius
      prolixus.
AB  - The effects of corticotropin-releasing factor (CRF)-related (ZooneDH), calcitonin
      (CT)-related (RhoprDH(31)) and kinin-related (leucokinin I) peptides on the ion
      composition of fluid secreted by upper Rhodnius prolixus Malpighian tubules and
      on KCl reabsorption by the lower tubules were assessed. ZooneDH stimulated fluid
      secretion while increasing the [Na(+)] of secreted fluid at the expense of
      [K(+)]. Upper tubules responded to ZooneDH with a characteristic triphasic change
      in the transepithelial potential (TEP), reminiscent of the response to 5
      hydroxytryptamine (5HT). RhoprDH(31) produced a small (~9 mV) lumen-positive
      shift in TEP of the upper tubule but had no effect on the rate of fluid secretion
      or ion composition of the secreted fluid. In contrast to 5HT, both peptides
      failed to activate KCl reabsorption by the lower tubule. Leucokinin I had no
      effect on the ion composition of fluid secreted by whole or upper Malpighian
      tubules. We propose that: (1) 5HT and a native CRF-related peptide similar to
      ZooneDH activate the same second messenger systems and ion transporters in the
      upper tubule cells; (2) CRF-related peptide is utilized to maintain high rates of
      fluid secretion during the post-feeding diuresis and is additionally used at
      times when KCl reabsorption is unnecessary or detrimental. The differential
      actions of multiple diuretic factors allows for intricate control of ionic and
      osmotic balance in R. prolixus.

PMID- 18083732
TI  - Heat increment of feeding in double-crested cormorants (Phalacrocorax auritus)
      and its potential for thermal substitution.
AB  - Diving endotherms inhabiting polar regions face potentially high thermoregulatory
      costs. Unless properly insulated, these animals will lose vast amounts of heat
      when diving in cold water, which has to be balanced by heat production. Heat
      generated as a by-product of digestion (heat increment of feeding, HIF) or from
      exercising muscles might be important in maintaining thermal balance under such
      conditions, as it would reduce the need for shivering thermogenesis. Recording
      the rate of oxygen consumption (V(O(2))), respiratory exchange ratio (RER), and
      stomach temperature, we studied the magnitude and duration of HIF in seven double
      crested cormorants (Phalacrocorax auritus) following the voluntary ingestion of a
      single herring (Clupea pallasi) while birds rested in air. Conducting trials at
      thermoneutral (21.1+/-0.2 degrees C) and sub-thermoneutral temperatures (5.5+/
      0.7 degrees C), we investigated the potential of HIF for thermal substitution.
      After the ingestion of a 100 g herring at thermoneutral conditions, V(O(2))was
      elevated for an average of 328+/-28 min, during which time birds consumed 2697+/
      294 ml O(2) in excess of the resting rate. At sub-thermoneutral conditions,
      duration (228+/-6 min) and magnitude (1391+/-271 ml O(2)) of V(O(2))elevation
      were significantly reduced. This indicates that cormorants are able to use the
      heat generated as by-product of digestion to substitute for regulatory
      thermogenesis, if heat loss is sufficiently high. Altering meal size during sub
      thermoneutral trials, we also found that HIF in cormorants was significantly
      greater after larger food intake. Based on these experimental results, a simple
      calculation suggests that substitution from HIF might reduce the daily
      thermoregulatory costs of double-crested cormorants wintering in coastal British
      Columbia by approximately 38%. Magnitude of HIF and its potential for thermal
      substitution should be integrated into bioenergetic models to avoid
      overestimating energy expenditure in these top predators.

PMID- 18083733
TI  - A new method to quantify prey acquisition in diving seabirds using wing stroke
      frequency.
AB  - To understand the foraging strategies of free-ranging diving animals, time series
      information on both foraging effort and foraging success is essential. Theory
      suggests that wing stroke frequency for aerial flight should be higher in heavier
      birds. Based on this premise, we developed a new methodology using animal-borne
      accelerometers to estimate fine-scale temporal changes in body mass of a pursuit
      diving, piscivorous seabird, the European shag, Phalacrocorax aristotelis. We
      hypothesized that variations in body mass determined from changes in wing stroke
      frequency before and after a series of dives would be related to the amount of
      prey captured. The estimated net gain in body mass during a foraging trip was
      highly variable, ranging from -30 to 260 g, values that were extremely similar to
      food loads obtained from shags on the Isle of May in previous years using water
      offloading and nest balances. Load sizes estimated using the wing stroke method
      were strongly and positively related to both cumulative flight time and return
      flight time. At the trip level, load size was unrelated to cumulative dive bout
      duration and the total amount of time spent underwater. However, highly
      significant relationships were apparent at the individual bout level, with birds
      showing bigger mass gains following longer dive bouts. Results from this study
      are therefore extremely encouraging and suggest that changes in body mass
      determined from changes in wing stroke frequency may provide a reliable method of
      obtaining short- to medium-term information on foraging effort and success of
      diving seabirds.

PMID- 18083734
TI  - Singing with reduced air sac volume causes uniform decrease in airflow and sound
      amplitude in the zebra finch.
AB  - Song of the zebra finch (Taeniopygia guttata) is a complex temporal sequence
      generated by a drastic change to the regular oscillations of the normal
      respiratory pattern. It is not known how respiratory functions, such as supply of
      air volume and gas exchange, are controlled during song. To understand the
      integration between respiration and song, we manipulated respiration during song
      by injecting inert dental medium into the air sacs. Increased respiratory rate
      after injections indicates that the reduction of air affected quiet respiration
      and that birds compensated for the reduced air volume. During song, air sac
      pressure, tracheal airflow and sound amplitude decreased substantially with each
      injection. This decrease was consistently present during each expiratory pulse of
      the song motif irrespective of the air volume used. Few changes to the temporal
      pattern of song were noted, such as the increased duration of a minibreath in one
      bird and the decrease in duration of a long syllable in another bird. Despite the
      drastic reduction in air sac pressure, airflow and sound amplitude, no increase
      in abdominal muscle activity was seen. This suggests that during song, birds do
      not compensate for the reduced physiological or acoustic parameters. Neither
      somatosensory nor auditory feedback mechanisms appear to effect a correction in
      expiratory effort to compensate for reduced air sac pressure and sound amplitude.

PMID- 18083735
TI  - A cumulative feeding threshold required for vitellogenesis can be obviated with
      juvenile hormone treatment in lubber grasshoppers.
AB  - Developmental thresholds can ensure that an adequate condition has been attained
      to proceed through major transitions (e.g. initiation of reproduction,
      metamorphosis). Nutrition is critical to attaining most thresholds, because it is
      needed for both growth and storage. Attaining a threshold typically stimulates
      the release of hormones that commit the animal to the developmental transition,
      yet the relationships between the nutrition needed for developmental thresholds
      and these endocrine signals are poorly understood. Lubber grasshoppers require a
      cumulative feeding threshold to initiate vitellogenesis and potentially commit to
      oviposition. We tested the relative roles of the nutritional threshold and the
      major gonadotropin (juvenile hormone; JH) in initiating vitellogenesis and
      committing to oviposition. The source of JH was removed from all females, and
      then JH analog was applied after different amounts of feeding. Threshold feeding
      was not required to initiate vitellogenesis, suggesting that sub-threshold
      grasshoppers are competent to respond to JH. Further, sub-threshold grasshoppers
      went on to oviposit earlier than supra-threshold grasshoppers treated with JH at
      the same time. Hence, threshold feeding is required only to cause the production
      and release of JH. At the same time, we also found that individuals that were
      restored with JH late in life tended to favor current reproduction, at the
      expense of future reproduction. Both time to oviposition and vitellogenin
      profiles were consistent with this developmental allocation. Taken together, our
      results suggest that lubber grasshoppers adjust reproductive tactics primarily in
      response to nutrition (which only serves to release JH) and secondarily in
      response to age.

PMID- 18083736
TI  - Morphological and mechanical determinants of bite force in bats: do muscles
      matter?
AB  - Bats are one of the most diverse groups of mammals and have radiated into a wide
      variety of trophic niches. Accordingly, the cranial structure in bats is
      unusually variable among mammals and thought to reflect specializations for
      feeding and echolocation. However, recent analyses of cranial structure, feeding
      behavior and bite force across a wide range of bats suggest that correlations
      between morphology and performance and/or ecology are not as clearcut as
      previously thought. For example, most of the variation in bite force across a
      wide range of phyllostomid bats was explained by differences in body size rather
      than specific cranial traits. However, remarkably little is known about the
      muscular components that are responsible for generating the actual bite forces.
      We have tested which aspects of the cranial muscular system are good predictors
      of bite force across a wide range of species using a modeling approach. Model
      calculations of bite force show good correspondence with in vivo data suggesting
      that they can be used to estimate performance of the cranial system. Moreover,
      our data show that bite force is strikingly well explained by differences in
      temporalis muscle mass, temporalis fiber length and masseter muscle mass.
      Moreover, our data show that evolutionary changes in bite force capacity in bats
      are associated with evolutionary changes in relative m. temporalis mass and
      absolute skull length.

PMID- 18083738
TI  - Jamming avoidance response of big brown bats in target detection.
AB  - When searching for prey, big brown bats (Eptesicus fuscus) enhance the range of
      their sonar by concentrating more energy in the nearly constant-frequency (CF)
      tail portion of their frequency-modulated (FM) sweeps. We hypothesize that this
      portion of their signals may be vulnerable to interference from conspecifics
      using the same frequencies in their own emissions. To determine how bats modify
      their signals when confronted with an interfering stimulus, we compared the
      echolocation calls of bats when a CF jamming tone was on and off. The bats
      performed a two-alternative forced-choice detection task in the laboratory that
      required the use of echolocation. All three bats shifted the tail-end CF
      component of their emitted frequency bidirectionally away from the CF jamming
      stimulus only when the jamming frequency was within 2-3 kHz of the preferred
      baseline frequency of the bat. The duration of their emissions did not differ
      between the jamming and no-jamming trials. The jamming avoidance response of bats
      may serve to avoid masking or interference in a narrow range of frequencies
      important for target detection.

PMID- 18083737
TI  - Conservation of structure, signaling and pharmacology between two serotonin
      receptor subtypes from decapod crustaceans, Panulirus interruptus and Procambarus
      clarkii.
AB  - Serotonin (5-HT) plays important roles in the maintenance and modulation of
      neural systems throughout the animal kingdom. The actions of 5-HT have been well
      characterized for several crustacean model circuits; however, a dissection of the
      serotonergic transduction cascades operating in these models has been hampered by
      the lack of pharmacological tools for invertebrate receptors. Here we provide
      pharmacological profiles for two 5-HT receptors from the swamp crayfish,
      Procambarus clarkii: 5-HT(2beta) and 5-HT(1alpha). In so doing, we also report
      the first functional expression of a crustacean 5-HT(1) receptor, and show that
      it inhibits accumulation of cAMP. The drugs mCPP and quipazine are 5-HT(1alpha)
      agonists and are ineffective at 5-HT(2beta). Conversely, methiothepin and
      cinanserin are antagonists of 5-HT(2beta) but do not block 5-HT(1alpha). A
      comparison of these two receptors with their orthologs from the California spiny
      lobster, Panulirus interruptus, indicates conservation of protein structure,
      signaling and pharmacology. This conservation extends beyond crustacean
      infraorders. The signature residues that form the ligand-binding pocket in
      mammalian 5-HT receptors are found in the crustacean receptors. Similarly, the
      protein domains involved in G protein coupling are conserved between the two
      crustacean receptors and other characterized arthropod and mammalian 5-HT
      receptors. Considering the apparent conservation of pharmacological properties
      between crustacean 5-HT receptors, these tools could be applicable to related
      crustacean physiological preparations.

PMID- 18083739
TI  - Antioxidative defence alterations in skeletal muscle during prolonged acclimation
      to cold: role of L-arginine/NO-producing pathway.
AB  - Early in cold acclimation (1-7 days), heat is produced by shivering, while late
      in cold acclimation (12-45 days), skeletal muscle contributes to thermogenesis by
      tissue metabolism other than contractions. Given that both thermogenic phases
      augment skeletal muscle aerobic power and reactive species production, we aimed
      in this study to examine possible changes in skeletal muscle antioxidative
      defence (AD) during early and late cold acclimation with special emphasis on the
      influence of the L-arginine/nitric oxide (NO)-producing pathway on the modulation
      of AD in this tissue. Adult Mill Hill hybrid hooded rat males were divided into
      two main groups: a control group, which was kept at room temperature (22+/-1
      degrees C), and a group maintained at 4+/-1 degrees C for 45 days. The cold
      acclimated group was divided into three subgroups: untreated, L-arginine treated
      and N(omega)-nitro-L-arginine methyl ester (L-NAME) treated. The AD parameters
      were determined in the gastrocnemius muscle on day 1, 3, 7, 12, 21 and 45 of cold
      acclimation. The results showed an improvement of skeletal muscle AD in both
      early and late cold acclimation. Clear phase-dependent changes were seen only in
      copper, zinc superoxide dismutase activity, which was increased in early cold
      acclimation but returned to the control level in late acclimation. In contrast,
      there were no phase-dependent changes in manganese superoxide dismutase,
      catalase, glutathione peroxidase, glutathione reductase and glutathione S
      transferase, the activities of which were increased during the whole cold
      exposure, indicating their engagement in both thermogenic phases. L-Arginine in
      early cold acclimation accelerated the cold-induced AD response, while in the
      late phase it sustained increases achieved in the early period. L-NAME affected
      both early and late acclimation through attenuation and a decrease in the AD
      response. These data strongly suggest the involvement of the L-arginine/NO
      pathway in the modulation of skeletal muscle AD.

PMID- 18083740
TI  - The thermal properties of beeswaxes: unexpected findings.
AB  - Standard melting point analyses only partially describe the thermal properties of
      eusocial beeswaxes. Differential scanning calorimetry (DSC) revealed that thermal
      phase changes in wax are initiated at substantially lower temperatures than
      visually observed melting points. Instead of a sharp, single endothermic peak at
      the published melting point of 64 degrees C, DSC analysis of Apis mellifera
      Linnaeus wax yielded a broad melting curve that showed the initiation of melting
      at approximately 40 degrees C. Although Apis beeswax retained a solid appearance
      at these temperatures, heat absorption and initiation of melting could affect the
      structural characteristics of the wax. Additionally, a more complete
      characterization of the thermal properties indicated that the onset of melting,
      melting range and heat of fusion of beeswaxes varied significantly among tribes
      of social bees (Bombini, Meliponini, Apini). Compared with other waxes examined,
      the relatively malleable wax of bumblebees (Bombini) had the lowest onset of
      melting and lowest heat of fusion but an intermediate melting temperature range.
      Stingless bee (Meliponini) wax was intermediate between bumblebee and honeybee
      wax (Apini) in heat of fusion, but had the highest onset of melting and the
      narrowest melting temperature range. The broad melting temperature range and high
      heat of fusion in the Apini may be associated with the use of wax comb as a free
      hanging structural material, while the Bombini and Meliponini support their wax
      structures with exogenous materials.

PMID- 18083741
TI  - Myogenesis and muscle metabolism in juvenile Atlantic salmon (Salmo salar) made
      transgenic for growth hormone.
AB  - Atlantic salmon (Salmo salar) made transgenic for growth hormone (GH) and non
      transgenic salmon were sampled at 4 and 7 months of age to estimate myogenic
      factors, satellite cell proliferation and metabolic enzyme activities. The growth
      rate of 4 month old transgenic salmon was higher than that of non-transgenic
      salmon. Myosatellite cell (MC) proliferation rates were higher in cells isolated
      from GH-transgenic salmon compared with cells from non-transgenic salmon of the
      same mass. Moreover, MCs extracted from non-transgenic salmon demonstrated a
      higher proliferation capacity when exposed in vitro to salmon GH. White muscle
      MyoD I mRNA content was higher in transgenic and non-transgenic salmon at 7
      months compared with that at 4 months, indicating an effect of age on MyoD I mRNA
      expression. White muscle myogenin mRNA content varied with fish age and presence
      of the transgene, and was higher in transgenic fish at 7 months, suggesting a
      higher differentiation capacity. MyoD I, MyoD II and myogenin mRNA content was
      higher in red muscle of GH-transgenic fish at 7 months compared with non
      transgenic salmon at 7 months. However, red muscle myogenic factor expression was
      not different between transgenic and non-transgenic fish of the same weight.
      Enzyme activities in white muscle and liver were highly affected by the presence
      of the transgene, although this effect was generally dependent on the age of the
      fish. Glycolytic and oxidative enzyme activities were increased in transgenic
      salmon liver, indicating a higher metabolic rate in transgenics. This study
      demonstrates that (1) the higher growth rate of transgenic salmon particularly at
      4 months of age could be explained at least in part by higher numbers and
      proliferation rates of MCs, (2) GH can directly stimulate the proliferation of
      myosatellite cells extracted from salmon, indicating that GH is one possible
      factor involved in the higher myosatellite cell proliferation rates in transgenic
      salmon, (3) MyoD and myogenin mRNA expression are affected by fish age, and (4)
      metabolic enzyme activities are affected by the age of the fish at least in liver
      and white muscle, and any transgene effect is dependent upon the age of the fish.

PMID- 18083742
TI  - Steady locomotion in dogs: temporal and associated spatial coordination patterns
      and the effect of speed.
AB  - Only a few studies on quadrupedal locomotion have investigated symmetrical and
      asymmetrical gaits in the same framework because the mechanisms underlying these
      two types of gait seem to be different and it took a long time to identify a
      common set of parameters for their simultaneous study. Moreover, despite the
      clear importance of the spatial dimension in animal locomotion, the relationship
      between temporal and spatial limb coordination has never been quantified before.
      We used anteroposterior sequence (APS) analysis to analyse 486 sequences from
      five malinois (Belgian shepherd) dogs moving at a large range of speeds (from 0.4
      to 10.0 m s(-1)) to compare symmetrical and asymmetrical gaits through kinematic
      and limb coordination parameters. Considerable continuity was observed in cycle
      characteristics, from walk to rotary gallop, but at very high speeds an increase
      in swing duration reflected the use of sagittal flexibility of the vertebral axis
      to increase speed. This change occurred after the contribution of the increase in
      stride length had become the main element driving the increase in speed - i.e.
      when the dogs had adopted asymmetrical gaits. As the left and right limbs of a
      pair are linked to the same rigid structure, spatial coordination within pairs of
      limbs reflected the temporal coordination within pairs of limbs whatever the
      speed. By contrast, the relationship between the temporal and spatial
      coordination between pairs of limb was found to depend on speed and trunk length.
      For trot and rotary gallop, this relationship was thought also to depend on the
      additional action of trunk flexion and leg angle at footfall.

PMID- 18083743
TI  - Locomotor function of forelimb protractor and retractor muscles of dogs: evidence
      of strut-like behavior at the shoulder.
AB  - The limbs of running mammals are thought to function as inverted struts. When
      mammals run at constant speed, the ground reaction force vector appears to be
      directed near the point of rotation of the limb on the body such that there is
      little or no moment at the joint. If this is true, little or no external work is
      done at the proximal joints during constant-speed running. This possibility has
      important implications to the energetics of running and to the coupling of lung
      ventilation to the locomotor cycle. To test if the forelimb functions as an
      inverted strut at the shoulder during constant-speed running and to characterize
      the locomotor function of extrinsic muscles of the forelimb, we monitored changes
      in the recruitment of six muscles that span the shoulder (the m. pectoralis
      superficialis descendens, m. pectoralis profundus, m. latissimus dorsi, m.
      omotransversarius, m. cleidobrachialis and m. trapezius) to controlled
      manipulations of locomotor forces and moments in trotting dogs (Canis lupus
      familiaris Linnaeus 1753). Muscle activity was monitored while the dogs trotted
      at moderate speed (approximately 2 m s(-1)) on a motorized treadmill. Locomotor
      forces were modified by (1) adding mass to the trunk, (2) inclining the treadmill
      so that the dogs ran up- and downhill (3) adding mass to the wrists or (4)
      applying horizontally directed force to the trunk through a leash. When the dogs
      trotted at constant speed on a level treadmill, the primary protractor muscles of
      the forelimb exhibited activity during the last part of the ipsilateral support
      phase and the beginning of swing phase, a pattern that is consistent with the
      initiation of swing phase but not with active protraction of the limb during the
      beginning of support phase. Results of the force manipulations were also
      consistent with the protractor muscles initiating swing phase and contributing to
      active braking via production of a protractor moment on the forelimb when the
      dogs decelerate. A similar situation appears to be true for the major retractor
      muscles of the forelimb. The m. pectoralis profundus and the m. latissimus dorsi
      were completely silent during the support phase of the ipsilateral limb when the
      dogs ran unencumbered and exhibited little or no increase in activity when the
      dogs carried added mass on their backs to increase any retraction torque during
      the support phase of constant-speed running. The most likely explanation for
      these observations is that the ground force reaction vector is oriented very
      close to the fulcrum of the forelimb such that the forelimb functions as a
      compliant strut at the shoulder when dogs trot at constant speed on level
      surfaces. Because the moments at the fulcrum of the pectoral girdle appear to be
      small during the support phase of a trotting step, a case can be made that it is
      the activity of the extrinsic appendicular muscles that produce the swing phase
      of the forelimb that explain the coupled phase relationship between ventilatory
      airflow and the locomotor cycle in trotting dogs.

PMID- 18083744
TI  - Sperm aneuploidy frequencies analysed before and after chemotherapy in testicular
      cancer and Hodgkin's lymphoma patients.
AB  - BACKGROUND Multicolour fluorescent in situ hybridization was utilized to detect
      sperm aneuploidy for chromosomes 13, 21, X and Y in testicular cancer and
      Hodgkin's lymphoma chemotherapy patients. METHODS Aneuploidy was assessed before,
      and 6, 12 and/or 18-24 months after, the initiation of chemotherapy, and compared
      with age matched controls. 635 396 sperm were scored blindly with 5000
      sperm/patient/chromosome/ time point, where sperm was available. (First two
      phrases have been reversed). RESULTS Comparing testicular cancer and Hodgkin's
      lymphoma patients to each other and with controls, cancer-specific differences
      were identified. Hodgkin's lymphoma patients, particularly, exhibited
      significantly increased aneuploidy frequencies for all chromosomes throughout
      treatment. At 6 months, all cancer patients showed significantly increased
      frequencies of XY disomy and nullisomy for chromosomes 13 and 21. In general,
      aneuploidy frequencies declined to pretreatment levels 18 months after treatment
      initiation, but increased aneuploidy frequencies persisted in some chromosomes
      for up to 24 months. CONCLUSIONS Because of elevated aneuploidy frequencies prior
      to and up to 24 months from the start of chemotherapy, patients should receive
      genetic counselling about the potentially increased risk of an aneuploid
      conceptus from sperm cryopreserved prior to chemotherapy, and for conceptions up
      to 2 years after the initiation of treatment.

PMID- 18083745
TI  - Bulk vitrification of human embryonic stem cells.
AB  - BACKGROUND: The traditional vitrification method cannot keep up with the
      increased culture and propagation efficiency required to cryopreserve large
      quantities of vigorously proliferating human embryonic stem (HES) cells. In this
      study, we describe a newly invented vitrification carrier for cryopreserving
      large amount of HES cells and evaluate whether this bulk vitrification (BV)
      method is as effective as the popular open-pulled straw (OPS) vitrification
      method. METHODS: HES cell clumps were harvested after passage and transferred to
      a cell strainer; only those clumps with a diameter more than 70 microm were
      included in the study and randomly selected to be cryopreserved by the BV method,
      OPS vitrification or slow freezing method. HES cell survival, growth and
      pluripotency were analyzed after thawing. RESULTS: Bulk vitrification method with
      cell strainer could cryopreserve 136 +/- 23.4 cell clumps at one time (round),
      which was 30 times as high as those for OPS method (4 +/- 1.5). After thawing,
      bulk-vitrified HES cells exhibited high survival rate up to 94.3%, comparable
      with the OPS method. All surviving cell clumps generated HES cell colonies.
      Teratomas comprising all three primordial germ layers were formed in severe
      combined immunodeficient mice after subcutaneous injection of post-thawed, bulk
      vitrified HES cell clumps, confirming pluripotency. CONCLUSIONS: This new BV
      method could cryopreserve a large quantity of HES cell clumps at one time, which
      not only would satisfy routine cryopreservation of HES cell during daily culture
      process but also guarantee researchers have large quantity of efficiently
      cryopreserved HES cells ready for a scheduled study at any time.

PMID- 18083746
TI  - Cyproterone acetate/ethinyl estradiol for acne and hirsutism: time to revise
      prescribing policy.
AB  - Clinical manifestations of androgen excess-hirsutism, acne and alopecia-are very
      common and distressing symptoms in women of reproductive age. These symptoms are
      frequently associated with polycystic ovary syndrome, in which condition
      menstrual disturbances are also common. The combination of the anti-androgen
      cyproterone acetate (2 mg) and ethinyl estradiol (35 microg) (co-cypridiol) is of
      proven efficacy in management of symptoms of both hyperandrogenism and menstrual
      abnormalities but its long-term use has been discouraged because of concern about
      increased risk of venous thromboembolism. In this article, we review the evidence
      for efficacy and adverse effects and conclude that its benefits are clear and
      that the risks of venous thromboembolism are no more common that with the use of
      third generation combined oral contraceptives.

PMID- 18083747
TI  - Endometrial thickness measured by ultrasound scan in women with uterine outlet
      obstruction due to intrauterine or upper cervical adhesions.
AB  - BACKGROUND: A subgroup of women with Asherman's syndrome has adhesions of limited
      extent completely blocking the lower uterine cavity or upper cervix, whereas the
      upper endometrium remains normal. Haematometra are rarely found in these women.
      We tested the hypothesis that women with localized adhesions occluding the
      uterine outlet (but not affecting the upper uterine cavity) will have much
      thinner endometrium than controls. METHODS: Twenty-six women with Asherman's
      syndrome (16 with limited outlet adhesions only) and 50 with normal menstrual
      cycles underwent transvaginal ultrasound scan where endometrial double thickness
      was measured precisely and the cycle phase assessed. The presence of any fluid in
      the uterine cavity was noted. RESULTS: The endometrium in women with Asherman's
      syndrome, in whom uterine outlet blockage was the sole abnormality (subgroup 3),
      was substantially thinner (mean +/- SEM: 3.9 +/- 0.4 mm) than controls (8.5 +/-
      0.05; P < 0.001), and haematometra were very uncommon (1 of 16). Endometrial
      thickness at all stages of the ovarian/menstrual cycle in all three subgroups of
      Asherman's syndrome was significantly less than in normal menstruating controls.
      CONCLUSIONS: Non-invasive ultrasound measurements have demonstrated very thin
      endometrium and absence of haematometra in most women with uterine outlet
      occlusion by adhesions. This unusual phenomenon of failure of cyclical
      endometrial growth and breakdown in the sole presence of cervical occlusion by
      adhesions merits further study.

PMID- 18083749
TI  - The role of sperm aneuploidy as a predictor of the success of intracytoplasmic
      sperm injection?
AB  - BACKGROUND: We present the first powered prospective study to assess whether
      sperm aneuploidy can predict the outcome of ICSI. METHODS: Our null hypothesis
      was that aneuploidy rates (AR) are identical in men who achieve successful (Group
      A) and unsuccessful (Group B) ICSI outcome. A power calculation yielded a sample
      number of 56 to achieve 80% power to reject our hypothesis at the 5% significance
      level. Samples for testing were obtained on the day of embryo transfer and tests
      were performed on raw pre-preparation samples. Sperm AR of chromosomes 13, 18,
      21, X/Y were assessed using fluorescence in-situ hybridization (FISH) techniques
      (mean of 1223 sperm). RESULTS: There was no significant difference in any
      patient, seminal, cycle or laboratory characteristic between groups that may have
      affected outcome. Total AR (2.37 versus 1.18%, P = 0.01), as well as AR of
      chromosomes 18, X/Y and 18 + X/Y (1.48 versus 0.67%, P = 0.005) were
      significantly higher in Group B compared with Group A. Regression analysis
      confirmed these differences to be independent of other variables and showed a 2.6
      fold change in odds of achieving a pregnancy for every 1% change in total AR.
      CONCLUSIONS: Our findings confirm a potential role for aneuploidy testing in the
      work-up of ICSI patients as a predictor of success, as well as in future genetic
      counselling. If confirmed, there may also be a place for a study of
      preimplantation genetic screening to improve ICSI success in men found to have
      high AR and ICSI failure.

PMID- 18083748
TI  - Urinary hCG patterns during the week following implantation.
AB  - BACKGROUND: Human chorionic gonadotrophin (hCG) is used to monitor pregnancy
      status. Yet the pattern of hCG excretion in the first week following implantation
      has not been adequately described. Therefore the aim of this study was to
      describe the average profile of hCG and its variability during the 7 days
      following estimated implantation in a population of naturally conceived
      pregnancies. METHODS: We measured daily hCG concentrations in first-morning urine
      for 142 clinical pregnancies from women with no known fertility problems. Mixed
      effects regression models were used to estimate the hCG trajectory and its
      variability in relation to pregnancy outcomes. RESULTS: hCG rose 3-fold between
      the day of detection and the next day (95% CI = 2.7-3.4). The relative rate of
      rise decreased thereafter, reaching 1.6-fold (95% CI = 1.5-1.8) between days 6
      and 7. HCG levels followed a log-quadratic trajectory, and the patterns of rise
      were unrelated to number of fetuses, risk of spontaneous abortion or sex of the
      baby. Later implantations (after 10 luteal days) produced slower rates of
      increase. CONCLUSIONS: Although mean hCG follows a log-quadratic trajectory
      during the first week of detectability, there is high variability across
      pregnancies. Later implantation may reflect characteristics of the uterus or
      conceptus that slow hCG production.

PMID- 18083750
TI  - Association between HIV replication and cholesterol in peripheral blood
      mononuclear cells in HIV-infected patients interrupting HAART.
AB  - BACKGROUND: Cellular cholesterol is essential for HIV replication and may control
      HIV spread. HIV, in turn, appears to control cholesterol metabolism. OBJECTIVES:
      To describe the relationships between serum lipids, cellular cholesterol and
      viral replication during highly active antiretroviral therapy (HAART)
      interruption. METHODS: We have correlated virological parameters with the level
      of circulating lipids in serum and the content of cellular cholesterol in
      peripheral blood mononuclear cells (PBMCs). The study included 33 patients
      interrupting HAART with (n = 23) or without (n = 10) atorvastatin treatment.
      RESULTS: Atorvastatin treatment did not modify PBMC cholesterol levels at week 4
      after HAART interruption, although it significantly reduced serum cholesterol
      (total and LDL, where LDL stands for low density lipoprotein) (P < 0.05). Serum
      cholesterol or LDL marginally influenced PBMC cholesterol since no significant
      correlations were found between these parameters either at 0 or 4 weeks after
      HAART interruption. Analysis of virological data in all patients revealed a
      negative trend (P = 0.07) between baseline PBMC cholesterol and absolute CD4 T
      cell counts at baseline but a poor correlation (P = 0.18) with the viral load
      (VL) at week 4. Separate analysis of control patients showed a correlation
      between baseline PBMC cholesterol and VL at week 4 (P = 0.01). However,
      atorvastatin treatment abrogated this correlation by increasing viral replication
      in individuals with low cellular cholesterol. CONCLUSIONS: Our data underscore
      the potential relevance of PBMC cholesterol in in vivo HIV replication and the
      complex effects of atorvastatin that seem to be unrelated to PBMC cholesterol.

PMID- 18083752
TI  - Properties of in vivo interictal spike generation in the human subiculum.
AB  - A large proportion of hippocampal afferents and efferents are relayed through the
      subiculum. It is also thought to be a key structure in the generation and
      maintenance of epileptic activity; rhythmic interictal-like discharges were
      recorded in previous studies of subicular slices excised from temporal lobe
      epilepsy patients. In order to investigate if and how the subiculum is involved
      in the generation of epileptic discharges in vivo, subicular and lateral temporal
      lobe electrical activity were recorded under anesthesia in 11 drug-resistant
      epilepsy patients undergoing temporal lobectomy. Based on laminar field potential
      gradient, current source density, multiple unit activity (MUA) and spectral
      analyses, two types of interictal spikes were distinguished in the subiculum. The
      more frequently occurring spike started with an initial excitatory current
      (current source density sink) in the pyramidal cell layer associated with
      increased MUA in the same location, followed by later inhibitory currents
      (current source density source) and decreased MUA. In the other spike type, the
      initial excitation was confined to the apical dendritic region and it was
      associated with a less-prominent increase in MUA. Interictal spikes were highly
      synchronized at spatially distinct locations of the subiculum. Laminar data
      showed that the peak of the initial excitation occurred within 0-4 ms at
      subicular sites separated by 6 mm at the anterior-posterior axis. In addition,
      initial spike peak amplitudes were highly correlated in most recordings. A subset
      of subicular and temporal lobe spikes were also highly synchronous, in one case
      the subicular spikes reliably preceded the temporal lobe discharges. Our results
      indicate that multiple spike generator mechanisms exist in the human epileptic
      subiculum suggesting a complex network interplay between medial and lateral
      temporal structures during interictal epileptic activity. The observed widespread
      intra-subicular synchrony may reflect both of its intrinsic and extrinsically
      triggered activity supporting the hypothesis that subiculum may also play an
      active role in the distribution of epileptiform activity to other brain regions.
      Limited data suggest that subiculum might even play a pacemaker role in the
      generation of paroxysmal discharges.

PMID- 18083753
TI  - Diffusion tensor imaging during recovery from severe traumatic brain injury and
      relation to clinical outcome: a longitudinal study.
AB  - Diffusion tensor imaging (DTI) has been proposed as a sensitive biomarker of
      traumatic white matter injury, which could potentially serve as a tool for
      prognostic assessment and for studying microstructural changes during recovery
      from traumatic brain injury (TBI). However, there is a lack of longitudinal
      studies on TBI that follow DTI changes over time and correlate findings with long
      term clinical outcome. We performed a prospective longitudinal study of 30 adult
      patients admitted for subacute rehabilitation following severe traumatic brain
      injury. DTI and conventional MRI were acquired at mean 8 weeks (5-11 weeks), and
      repeated in 23 of the patients at mean 12 months (9-15 months) post-trauma. Using
      a region-of-interest-based approach, DTI parameters were compared to those of
      healthy matched controls, scanned during the same time period and rescanned with
      a similar interval as that of patients. At the initial scan, fractional
      anisotropy was reduced in all the investigated white matter regions in patients
      compared to controls (P <or= 0.01) due to decreased diffusivity parallel
      (lambda(parallel)) and increased diffusivity perpendicular
      (lambda(perpendicular)) to axonal fibre direction. Fractional anisotropy in the
      cerebral peduncle correlated with approximately 1 year Glasgow outcome scale
      score (r = 0.60, P<0.001) and in this sample predicted dichotomized outcome with
      76% accuracy when taken alone, and with 100% accuracy in combination with
      clinical evaluation by functional independence measure at the time of the first
      scan. At follow-up DTI, fractional anisotropy in patients had increased in the
      internal capsule and in centrum semiovale (P <or= 0.01) due to an interval
      increase of lambda(parallel) with unchanged lambda(perpendicular). In these
      regions, fractional anisotropy and lambda( parallel) reached normal or
      supranormal levels, primarily in patients with favourable outcome. In the
      cerebral peduncle and in corpus callosum, lambda(parallel) and
      lambda(perpendicular) both increased during the scan interval and, particularly
      in patients with unfavourable outcome, fractional anisotropy remained depressed.
      No significant DTI parameter changes over time were found in controls, or in CSF
      of patients. These findings support that DTI is a clinically relevant biomarker
      in TBI, which may have prognostic value and also might serve as a tool for
      revealing changes in the neural tissue during recovery.

PMID- 18083751
TI  - Focal white matter changes in spasmodic dysphonia: a combined diffusion tensor
      imaging and neuropathological study.
AB  - Spasmodic dysphonia is a neurological disorder characterized by involuntary
      spasms in the laryngeal muscles during speech production. Although the clinical
      symptoms are well characterized, the pathophysiology of this voice disorder is
      unknown. We describe here, for the first time to our knowledge, disorder-specific
      brain abnormalities in these patients as determined by a combined approach of
      diffusion tensor imaging (DTI) and postmortem histopathology. We used DTI to
      identify brain changes and to target those brain regions for neuropathological
      examination. DTI showed right-sided decrease of fractional anisotropy in the genu
      of the internal capsule and bilateral increase of overall water diffusivity in
      the white matter along the corticobulbar/corticospinal tract in 20 spasmodic
      dysphonia patients compared to 20 healthy subjects. In addition, water
      diffusivity was bilaterally increased in the lentiform nucleus, ventral thalamus
      and cerebellar white and grey matter in the patients. These brain changes were
      substantiated with focal histopathological abnormalities presented as a loss of
      axonal density and myelin content in the right genu of the internal capsule and
      clusters of mineral depositions, containing calcium, phosphorus and iron, in the
      parenchyma and vessel walls of the posterior limb of the internal capsule,
      putamen, globus pallidus and cerebellum in the postmortem brain tissue from one
      patient compared to three controls. The specificity of these brain abnormalities
      is confirmed by their localization, limited only to the
      corticobulbar/corticospinal tract and its main input/output structures. We also
      found positive correlation between the diffusivity changes and clinical symptoms
      of spasmodic dysphonia (r = 0.509, P = 0.037). These brain abnormalities may
      alter the central control of voluntary voice production and, therefore, may
      underlie the pathophysiology of this disorder.

PMID- 18083754
TI  - No reversal of the Oppel-Kundt illusion with short stimuli: confutation of the
      space anisometry interpretation of neglect and 'cross-over' in line bisection.

PMID- 18083755
TI  - Good governance for the public's health.

PMID- 18083756
TI  - Patient organizations and public health.

PMID- 18083757
TI  - WHO regional office for Europe: can tuberculosis be contained in the European
      Region?

PMID- 18083758
TI  - 'Ethnic cleansing' and 'genocide'.

PMID- 18083759
TI  - The case for large scale fungible cohorts.

PMID- 18083761
TI  - Impact of different stages of chronic kidney disease on in-hospital costs in
      patients with coronary heart disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with markedly increased in
      hospital morbidity and mortality. Its effect on in-hospital costs for the
      treatment of coronary heart disease (CHD) has not been assessed that, although it
      is of interest due to the exponential increase in its prevalence. METHODS:
      Clinical and costing data were retrospectively assessed from 765 consecutive
      patients who suffered from CHD requiring percutaneous coronary interventions.
      Based on their estimated glomerular filtration rate (eGFR), patients were
      classified in accordance with the National Kidney Foundation. Patient-level in
      hospital costs for this single hospitalization were thoroughly calculated from
      precise in-house assessments for the national DRG database. RESULTS: In
      univariate analysis, the average total in-hospital costs increased with each
      stage of CKD [euro2926; euro3466; euro4208; euro9687 (stages 4 and 5 combined), P
      < 0.0001]. Treating patients with CKD stages 4 and 5 utilized markedly more
      resources than patients with ST-elevation myocardial infarction (euro4916),
      coronary three-vessel disease (euro4659), severely impaired left ventricular
      function (euro6072) or diabetes (euro4495). Multivariate analyses identified,
      even after adjustment for confounding comorbidities, that CKD was a significant
      and independent predictor of in-hospital costs; with each loss of 1 ml/min in the
      eGFR, the expenses for this hospitalization increased by euro18 (95% CI euro13
      23). CONCLUSIONS: Although the absolute amount of costs may vary between
      different countries, this work showed, for the first time, that in all stages of
      CKD, there is a significant increase of in-hospital costs when treating patients
      with both CHD and CKD.

PMID- 18083760
TI  - Contributions of DNA interstrand cross-links to aging of cells and organisms.
AB  - Impaired DNA damage repair, especially deficient transcription-coupled nucleotide
      excision repair, leads to segmental progeroid syndromes in human patients as well
      as in rodent models. Furthermore, DNA double-strand break signalling has been
      pinpointed as a key inducer of cellular senescence. Several recent findings
      suggest that another DNA repair pathway, interstrand cross-link (ICL) repair,
      might also contribute to cell and organism aging. Therefore, we summarize and
      discuss here that (i) systemic administration of anti-cancer chemotherapeutics,
      in many cases DNA cross-linking drugs, induces premature progeroid frailty in
      long-term survivors; (ii) that ICL-inducing 8-methoxy-psoralen/UVA phototherapy
      leads to signs of premature skin aging as prominent long-term side effect and
      (iii) that mutated factors involved in ICL repair like ERCC1/XPF, the Fanconi
      anaemia proteins, WRN and SNEV lead to reduced replicative life span in vitro and
      segmental progeroid syndromes in vivo. However, since ICL-inducing drugs cause
      damage different from ICL and since all currently known ICL repair factors work
      in more than one pathway, further work will be needed to dissect the actual
      contribution of ICL damage to aging.

PMID- 18083762
TI  - Parvalbumin: a key protein in early distal tubule NaCl reabsorption.

PMID- 18083763
TI  - Thrombin enhances the barrier function of rat microvascular endothelium in a PAR
      1-dependent manner.
AB  - Thrombin is a multifunctional coagulation protease with pro- and anti
      inflammatory vascular effects. We questioned whether thrombin may have
      segmentally differentiated effects on pulmonary endothelium. In cultured rat
      endothelial cells, rat thrombin (10 U/ml) recapitulated the previously reported
      decrease in transmonolayer electrical resistance (TER), F-actin stress fiber
      formation, paracellular gap formation, and increased permeability. In contrast,
      in rat pulmonary microvascular endothelial cells (PMVEC), isolated on the basis
      of Griffonia simplicifolia lectin recognition, thrombin increased TER, induced
      fewer stress fibers, and decreased permeability. To assess for differential
      proteinase-activated receptor (PAR) expression as a basis for the different
      responses, PAR family expression was analyzed. Both pulmonary artery endothelial
      cells and PMVEC expressed PAR-1 and PAR-2; however, only PMVEC expressed PAR-3,
      as shown by both RT-PCR and Western analysis. PAR-1 activating peptides (PAR-APs:
      SFLLRN-NH(2) and TFLLRN-NH(2)) were used to confirm a role for the PAR-1
      receptor. PAR-APs (25-250 muM) also increased TER, formed fewer stress fibers,
      and did not induce paracellular gaps in PMVEC in contrast to that shown in
      pulmonary artery endothelial cells. These results were confirmed in isolated
      perfused rat lung preparations. PAR-APs (100 mug/ml) induced a 60% increase in
      the filtration coefficient over baseline. However, by transmission electron
      microscopy, perivascular fluid cuffs were seen only along conduit veins and
      arteries without evidence of intra-alveolar edema. We conclude that thrombin
      exerts a segmentally differentiated effect on endothelial barrier function in
      vitro, which corresponds to a pattern of predominant perivascular fluid cuff
      formation in situ. This may indicate a distinct role for thrombin in the
      microcirculation.

PMID- 18083764
TI  - Role of PAR2 in murine pulmonary pseudomonal infection.
AB  - Proteinases can influence lung inflammation by various mechanisms, including via
      cleavage and activation of protease-activated receptors (PAR) such as PAR2. In
      addition, proteinases such as neutrophil and/or Pseudomonas-derived elastase can
      disarm PAR2 resulting in loss of PAR2 signaling. Currently, the role of PAR2 in
      host defense against bacterial infection is not known. Using a murine model of
      acute Pseudomonas aeruginosa pneumonia, we examined differences in the pulmonary
      inflammatory response between wild-type and PAR2(-/-) mice. Compared with wild
      type mice, PAR2(-/-) mice displayed more severe lung inflammation and injury in
      response to P. aeruginosa infection as indicated by higher bronchoalveolar lavage
      fluid neutrophil numbers, protein concentration, and TNF-alpha levels. By
      contrast, IFN-gamma levels were markedly reduced in PAR2(-/-) compared with wild
      type mice. Importantly, clearance of P. aeruginosa was diminished in PAR2(-/-)
      mice. In vitro testing revealed that PAR2(-/-) neutrophils killed significantly
      less bacteria than wild-type murine neutrophils. Further, both neutrophils and
      macrophages from PAR2(-/-) mice displayed significantly reduced phagocytic
      efficiency compared with wild-type phagocytes. Stimulation of PAR2 on macrophages
      using a PAR2-activating peptide resulted in enhanced phagocytosis directly
      implicating PAR2 signaling in the phagocytic process. We conclude that genetic
      deletion of PAR2 is associated with decreased clearance of P. aeruginosa. Our
      data suggest that a deficiency in IFN-gamma production and impaired bacterial
      phagocytosis are two potential mechanisms responsible for this defect.

PMID- 18083765
TI  - Reactivation of gammaHV68 induces neointimal lesions in pulmonary arteries of
      S100A4/Mts1-overexpressing mice in association with degradation of elastin.
AB  - S100A4/Mts-overexpressing mice have thick elastic laminae and mild pulmonary
      arterial hypertension (PAH), and the occasional older mouse develops occlusive
      neointimal lesions and perivascular inflammation. We hypothesized that a
      vasculotropic virus could induce neointimal lesions in the S100A4/Mts1 mouse by
      facilitating breakdown of elastin and migration and proliferation of smooth
      muscle cells. To test this hypothesis, we infected S100A4/Mts1 mice with
      gammaherpesvirus 68 (gammaHV68). We observed, 6 mo after gammaHV68 [4 x 10(3)
      plaque-forming units (PFU)], perivascular inflammation in 10/15 S100A4/Mts1 mice
      and occlusive neointimal formation in 3/10 mice, accompanied by striking
      degradation of elastin. We then compared the early response after high-dose
      gammaHV68 (4 x 10(6) PFU) in C57Bl/6 and S100A4/Mts1 mice. In S100A4/Mts1 mice
      only, significant PAH, muscularization of distal vessels, and elastase activity
      were observed 6 wk after gammaHV68. These features resolved by 3 mo without
      neointimal formation. We therefore infected mice with the M1-gammaHV68 strain
      that reactivates from latency with higher efficiency and observed neointimal
      lesions at 3 mo in 2/5 C57Bl/6 (5-9% of vessels) and in 5/5 S100A4/Mts1 mice (13
      40% of vessels) accompanied by mild PAH, heightened lung elastase activity, and
      intravascular viral expression. This suggested that enhanced generation of
      elastin peptides in S100A4/Mts1 mice may promote increased viral entry in the
      vessel wall. Using S100A4/Mts1 PA organ culture, we showed, in response to
      elastase activity, heightened production of elastin peptides associated with
      invasion of inflammatory cells and intravascular viral antigen. We therefore
      propose that early viral access to the vessel wall may be a critical determinant
      of the extent of vascular pathology following reactivation.

PMID- 18083766
TI  - Compromised E-cadherin adhesion and epithelial barrier function with activation
      of G protein-coupled receptors is rescued by Y-to-F mutations in beta-catenin.
AB  - Activation of the type 1 histamine (H1) or the type 2 protease-activated (PAR-2)
      G protein-coupled receptors interrupts E-cadherin adhesion and decreases the
      transepithelial resistance (TER) of epithelium. Several reports suggest that
      cadherin adhesive function depends on the association of cadherin with beta
      catenin and that this association is regulated by phosphorylation of tyrosines in
      beta-catenin. We tested the hypothesis that loss of cadherin adhesion and
      compromise of TER on activation of the H1 or PAR-2 receptor is due to
      phosphorylation of tyrosines in beta-catenin. L cells were stably transfected to
      express E-cadherin (L-E-cad cells) and H1 (L-H1-E-cad cells). L cells and Madin
      Darby canine kidney (MDCK) cells constitutively express PAR-2. Stably transfected
      L-E-cad, L-H1-E-cad, and MDCK cells were also stably transfected with FLAG-tagged
      wild-type (WT) or mutant beta-catenin, converting tyrosine 142, 489, or 654 to
      the nonphosphorylatable mimetic, phenylalanine (WT, Y142F, Y489F, or Y654F).
      Activation of H1 or PAR-2 interrupted adhesion to an immobilized E-cadherin-Fc
      fusion protein of L-H1-E-cad, L-E-cad, and MDCK cells expressing WT or Y142F beta
      catenin but did not interrupt adhesion of L-H1-E-cad, L-E-cad, and MDCK cells
      expressing the Y489F or Y654F mutant beta-catenins. PAR-2 activation decreased
      the TER of monolayers of MDCK cells expressing WT or Y142F beta-catenin 40-45%.
      However, PAR-2 activation did not decrease the TER of monolayers of MDCK cells
      expressing Y489F or Y654F beta-catenin. The protein tyrosine phosphatase PTP1B
      binds to the cadherin cytoplasmic domain and dephosphorylates beta-catenin.
      Inhibition of PTP1B interrupted adhesion to E-cadherin-Fc of MDCK cells
      expressing WT beta-catenin but did not affect the adhesion of MDCK cells
      expressing Y489F or Y654F beta-catenin. Similarly, inhibition of PTP1B
      compromised the TER of MDCK cells expressing WT beta-catenin but did not affect
      the TER of MDCK cells expressing Y489F or Y654F beta-catenin. We conclude that
      phosphorylation of tyrosines 489 and 654 in beta-catenin is a necessary step in
      the process by which G protein-coupled H1 and PAR-2 receptors interrupt E
      cadherin adhesion. We also conclude that activation of PAR-2 has no effect on the
      TER without first interrupting E-cadherin adhesion.

PMID- 18083767
TI  - Cytoplasmic provenance of STAT3 and PY-STAT3 in the endolysosomal compartments in
      pulmonary arterial endothelial and smooth muscle cells: implications in pulmonary
      arterial hypertension.
AB  - Lung vascular lesions in pulmonary arterial hypertension (PAH) are characterized
      by enlarged, vacuolated ("megalocytotic") pulmonary arterial endothelial (PAEC)
      and smooth muscle cells (PASMC). We have recently proposed that dysfunction of
      vesicle tethers, soluble N-ethylmaleimide-sensitive factor attachment proteins
      (SNAPs), and SNAP receptors (SNAREs), leading to disruptions of intracellular
      trafficking in the Golgi to plasma membrane (centrifugal) and the plasma membrane
      to cell interior (centripetal) directions is a key causal mechanism in this
      disease. In PAH, there was a reciprocal relationship between loss of caveolin-1
      (cav-1) in PAECs and increased expression of "activated" tyrosine-phosphorylated
      STAT3 (PY-STAT3) associated with a block in centrifugal trafficking to/through
      the Golgi organelle. In the present study, we investigated 1) whether centripetal
      trafficking of STAT3 and PY-STAT3 in PAECs and PASMCs was membrane-associated,
      and 2) whether this might be affected in PAH. Immunofluorescence and live cell
      imaging studies showed that, in both PAEC and PASMC, STAT3 was associated with
      cytoplasmic vesicles partially colocalizing with markers of the endolysosomal
      compartments (clathrin, EEA1, Rab5, Rab11, and LAMP1). Overexpression of cav-1
      increased the targeting of STAT3 to lysosomes and inhibited STAT3 transcriptional
      activity. Exposure of PAECs to monocrotaline (MCT) pyrrole, which causes PAH in
      the rat, led to a loss of caveolar STAT3 with increased sequestration of STAT3
      and PY-STAT3 in endosomes. In vivo, marked cytoplasmic sequestration of activated
      PY-STAT3 was a common feature in PAEC in the rat/MCT model and in cells in the
      proliferative arterial and plexiform lesions in PAH in humans. These data
      highlight the epigenetic regulation of centripetal cytokine and growth-factor
      signaling pathways and its modulation in PAH.

PMID- 18083768
TI  - Surfactant protein-A plays an important role in lung surfactant clearance:
      evidence using the surfactant protein-A gene-targeted mouse.
AB  - Previous studies with the isolated perfused rat lung showed that both clathrin-
      and actin-mediated pathways are responsible for endocytosis of
      dipalmitoylphosphatidylcholine (DPPC)-labeled liposomes by granular pneumocytes
      in the intact lung. Using surfactant protein-A (SP-A) gene-targeted mice, we
      examined the uptake of [(3)H]DPPC liposomes by isolated mouse lungs under basal
      and secretagogue-stimulated conditions. Unilamellar liposomes composed of
      [(3)H]DPPC: phosphatidylcholine:cholesterol:egg phosphatidylglycerol (10:5:3:2
      mol fraction) were instilled into the trachea of anesthetized mice, and the lungs
      were perfused (2 h). Uptake was calculated as percentage of instilled
      disintegrations per minute in the postlavaged lung. Amantadine, an inhibitor of
      clathrin and, thus, receptor-mediated endocytosis via clathrin-coated pits,
      decreased basal [(3)H]DPPC uptake by 70% in SP-A +/+ but only by 20% in SP-A -/-
      lung, data compatible with an SP-A/receptor-regulated lipid clearance pathway in
      the SP-A +/+ mice. The nonclathrin, actin-dependent process was low in the SP-A
      +/+ lung but accounted for 55% of liposome endocytosis in the SP-A -/- mouse.
      With secretagogue (8-bromoadenosine 3',5'-cyclic monophosphate) treatment, both
      clathrin- and actin-dependent lipid clearance were elevated in the SP-A +/+ lungs
      while neither pathway responded in the SP-A -/- lungs. Binding of iodinated SP-A
      to type II cells isolated from both genotypes of mice was similar indicating a
      normal SP-A receptor status in the SP-A -/- lung. Inclusion of SP-A with
      instilled liposomes served to "rescue" the SP-A -/- lungs by reestablishing
      secretagogue-dependent enhancement of liposome uptake. These data are compatible
      with a major role for receptor-mediated endocytosis of DPPC by granular
      pneumocytes, a process critically dependent on SP-A.

PMID- 18083769
TI  - Carbon nanoparticle-induced lung epithelial cell proliferation is mediated by
      receptor-dependent Akt activation.
AB  - Treatment of lung epithelial cells with different kinds of nano-sized particles
      leads to cell proliferation. Because bigger particles fail to induce this
      reaction, it is suggested that the special surface properties, due to the
      extremely small size of these kinds of materials, is the common principle
      responsible for this specific cell reaction. Here the activation of the protein
      kinase B (Akt) signaling cascade by carbon nanoparticles was investigated with
      regard to its relevance for proliferation. Kinetics and dose-response experiments
      demonstrated that Akt is specifically activated by nanoparticulate carbon
      particles in rat alveolar type II epithelial cells as well as in human bronchial
      epithelial cells. This pathway appeared to be dependent on epidermal growth
      factor receptor and beta(1)-integrins. The activation of Akt by these receptors
      is known to be a feature of adhesion-dependent signaling. However, intracellular
      proteins described in this context (focal adhesion kinase pp125(FAK) and integrin
      linked kinase) were not activated, indicating a specific signaling mechanism.
      Inhibitor studies demonstrate that nanoparticle-induced proliferation is mediated
      by phosphoinositide 3-kinases and Akt. Moreover, overexpression of mutant Akt, as
      well as pretreatment with an Akt inhibitor, reduced nanoparticle-specific ERK1/2
      phosphorylation, which is decisive for nanoparticle-induced proliferation. With
      this report, we describe the activation of a pathway by carbon nanoparticles that
      was so far known to be triggered by ligand receptor binding or on cell adhesion
      to extracellular matrix proteins.

PMID- 18083770
TI  - Lung epithelial injury markers are not influenced by use of lower tidal volumes
      during elective surgery in patients without preexisting lung injury.
AB  - Clara cell protein levels are elevated in plasma of individuals with mild or
      subclinical lung injury. We studied the influence of two mechanical ventilation
      strategies on local and systemic levels of Clara cell protein (CC16) and compared
      them with levels of soluble receptor for advanced glycation end products (sRAGE)
      and surfactant proteins (SP)-A and -D in patients undergoing elective surgery.
      Saved samples from a previously reported investigation were used for the study.
      Forty patients planned for elective surgery were randomized to mechanical
      ventilation with either a conventional tidal volume (V(T)) of 12 ml/kg without
      positive end-expiratory pressure (PEEP) or low V(T) of 6 ml/kg and 10 cmH(2)O
      PEEP. Plasma and bronchoalveolar lavage fluid (BALF) was collected directly after
      intubation and after 5 h of mechanical ventilation. While systemic levels of SP-A
      and SP-D remained unchanged, systemic levels of CC16 and sRAGE increased
      significantly in both groups after 5 h (P < 0.001 for both). BALF levels of SP-A,
      SP-D, CC16, and sRAGE remained unaffected. No differences were found between the
      two mechanical ventilation strategies regarding any of the measured biological
      markers. In conclusion, systemic levels of CC16 and sRAGE rise after 5 h in
      patients receiving mechanical ventilation for elective surgery. Mechanical
      ventilation with lower tidal volumes and PEEP did not have a different effect on
      levels of biomarkers of lung epithelial injury compared with conventional
      mechanical ventilation.

PMID- 18083771
TI  - Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary
      hypertension in neonatal rats.
AB  - Xanthine oxidase (XO)-derived reactive oxygen species (ROS) formation contributes
      to experimental chronic hypoxic pulmonary hypertension in adults, but its role in
      neonatal pulmonary hypertension has received little attention. In rats
      chronically exposed to hypoxia (13% O(2)) for 14 days from birth, we examined the
      effects of ROS scavengers (U74389G 10 mg.kg(-1).day(-1) or Tempol 100 mg.kg(
      1).day(-1) ip) or a XO inhibitor, Allopurinol (50 mg.kg(-1).day(-1) ip). Both ROS
      scavengers limited oxidative stress in the lung and attenuated hypoxia-induced
      vascular remodeling, confirming a critical role for ROS in this model. However,
      both interventions also significantly inhibited somatic growth and normal
      cellular proliferation in distal air spaces. Hypoxia-exposed pups had evidence of
      increased serum and lung XO activity, increased vascular XO-derived superoxide
      production, and vascular nitrotyrosine formation. These changes were all
      prevented by treatment with Allopurinol, which also attenuated hypoxia-induced
      vascular remodeling and partially reversed inhibited endothelium-dependent
      arterial relaxation, without affecting normal growth and proliferation.
      Collectively, our findings suggest that XO-derived superoxide induces endothelial
      dysfunction, thus impairing pulmonary arterial relaxation, and contributes to
      vascular remodeling in hypoxia-exposed neonatal rats. Due to the potential for
      adverse effects on normal growth, targeting XO may represent a superior
      "antioxidant" strategy to ROS scavengers for neonates with pulmonary
      hypertension.

PMID- 18083772
TI  - Dietary flaxseed enhances antioxidant defenses and is protective in a mouse model
      of lung ischemia-reperfusion injury.
AB  - Dietary flaxseed (FS) is a nutritional whole grain with high contents of omega-3
      fatty acids and lignans with anti-inflammatory and antioxidant properties. We
      evaluated FS in a murine model of pulmonary ischemia-reperfusion injury (IRI) by
      dietary supplementation of 0% (control) or 10% (treatment) FS before IRI. Mice
      fed 0% FS undergoing IRI had a significant decrease in arterial oxygenation
      (Pa(O(2))) and a significant increase in bronchoalveolar lavage (BAL) protein
      compared with sham-operated mice. However, mice fed 10% FS undergoing IRI had a
      significant improvement in both Pa(O(2)) and BAL protein compared with mice fed
      0% FS undergoing IRI. In addition, oxidative lung damage was decreased in 10% FS
      supplemented mice undergoing IRI, as assessed by malondialdehyde levels.
      Immunohistochemical staining of lungs for iPF(2alpha)-III F(2) isoprostane, a
      measure of lipid oxidation, was diminished. FS-supplemented mice had less
      reactive oxygen species (ROS) release from the vascular endothelium in lungs in
      an ex vivo model of IRI, and alveolar macrophages isolated from FS-fed mice had
      significantly reduced ROS generation in response to oxidative burst. Pulmonary
      microvascular endothelial cells produced less ROS in a flow cessation model of
      ischemia when preincubated with purified FS lignan metabolites. Pharmacological
      inhibition of heme oxygenase-1 (HO-1) resulted in only a partial reduction of FS
      protection in the same model. We conclude that dietary FS is protective against
      IRI in an experimental murine model and that FS affects ROS generation and ROS
      detoxification via pathways not limited to upregulation of antioxidant enzymes
      such as HO-1.

PMID- 18083773
TI  - Is thoracoscopic surgery justified to treat pulmonary metastasis from colorectal
      cancer?
AB  - We retrospectively analyzed 143 consecutive patients undergoing pulmonary
      resection for metastasis from colorectal cancer, either through thoracotomy or
      thoracoscopy from 1987 to 2005. Patients with incomplete resection were excluded.
      Patients were divided into two groups, based on whether or not they underwent
      thoracoscopy (n=72) or open thoracotomy (n=71) at the first pulmonary
      metastasectomy. Two patients undergoing thoracoscopy died postoperatively (one
      from pulmonary thromboembolism and one from gastrointestinal bleeding). Factors
      influencing postoperative recurrence-free or overall survival were multiple
      pulmonary metastasis and history of liver metastasis by univariate analysis, and
      multiple pulmonary metastasis, hilar or mediastinal nodal metastasis, larger
      diameter of the pulmonary metastasis, and surgery by wedge resection by
      multivariate analysis. Five-year recurrence-free rates after the first pulmonary
      metastasectomy were 34.4% in thoracoscopy and 21.1% in thoracotomy, respectively
      (P=0.047). Overall 5-year survival rates were 49.3% in thoracoscopy and 39.5% in
      thoracotomy, respectively (not significant). We found no significant difference
      in the survival rates between the thoracotomy and thoracoscopy groups, even with
      elimination of the patients with multiple pulmonary metastases in both groups. We
      suggest that thoracoscopic surgery for pulmonary metastasectomy from colorectal
      cancer may be justified if the surgical treatment is indicated.

PMID- 18083774
TI  - Pacemaker-induced ventricular tachycardia.

PMID- 18083775
TI  - Gene number expansion and contraction in vertebrate genomes with respect to
      invertebrate genomes.
AB  - Where did vertebrate genes come from? Here we address this question by analyzing
      eight completely sequenced land vertebrate genomes and six completely sequenced
      invertebrate genomes. Approximately 70% of the vertebrate genes can be found in
      the six invertebrate genomes with the standard homology search criteria (denoted
      as V.MCL), another approximately 6% can be found with relaxed search criteria,
      and an additional approximately 2% can be found in sequenced fungal and bacterial
      genomes. Thus, a substantial proportion of vertebrate genes (approximately 22%)
      cannot be found in the nonvertebrate genomes studied (denoted as Vonly).
      Interestingly, genes in Vonly are predominantly singletons, while the majority of
      genes in the other three groups belong to gene families. The proteins of Vonly
      tend to evolve faster than those of V.MCL. Surprisingly, in many cases the family
      sizes in V.MCL are only as large as or even smaller than their counterparts in
      the invertebrates, contrary to the general perception of a larger family size in
      vertebrates. Interestingly, in comparison with the family size in invertebrates,
      vertebrate gene families involved in regulation, signal transduction,
      transcription, protein transport, and protein modification tend to be expanded,
      whereas those involved in metabolic processes tend to be contracted. Furthermore,
      for almost all of the functional categories with family size expansion in
      vertebrates, the number of gene types (i.e., the number of singletons plus the
      number of gene families) tends to be over-represented in Vonly, but under
      represented in V.MCL. Our study suggests that gene function is a major
      determinant of gene family size.

PMID- 18083776
TI  - Quantitative systems-level determinants of human genes targeted by successful
      drugs.
AB  - What makes a successful drug target? A target molecule with an appropriate
      (druggable) tertiary structure is a necessary but not the sufficient condition
      for success. Here we analyzed specific properties of human genes and proteins
      targeted by 919 FDA-approved drugs and identified several quantitative measures
      that distinguish them from other genes and proteins at a highly significant
      level. Compared to an average gene and its encoded protein(s), successful drug
      targets are more highly connected (but far from being the most highly connected),
      have higher betweenness values, lower entropies of tissue expression, and lower
      ratios of nonsynonymous to synonymous single-nucleotide polymorphisms.
      Furthermore, we have identified human tissues that are significantly over- or
      undertargeted relative to the full spectrum of genes that are active in each
      tissue. Our study provides quantitative guidelines that could aid in the
      computational screening of new drug targets in human cells.

PMID- 18083777
TI  - Short read fragment assembly of bacterial genomes.
AB  - In the last year, high-throughput sequencing technologies have progressed from
      proof-of-concept to production quality. While these methods produce high-quality
      reads, they have yet to produce reads comparable in length to Sanger-based
      sequencing. Current fragment assembly algorithms have been implemented and
      optimized for mate-paired Sanger-based reads, and thus do not perform well on
      short reads produced by short read technologies. We present a new Eulerian
      assembler that generates nearly optimal short read assemblies of bacterial
      genomes and describe an approach to assemble reads in the case of the popular
      hybrid protocol when short and long Sanger-based reads are combined.

PMID- 18083778
TI  - Inverse agonist and neutral antagonist actions of antidepressants at recombinant
      and native 5-hydroxytryptamine2C receptors: differential modulation of cell
      surface expression and signal transduction.
AB  - Despite the importance of 5-hydroxytryptamine (5-HT)(2C) (serotonin) receptors in
      the control of depressive states, actions of antidepressants at these receptors
      remain poorly characterized. This issue was addressed both in human embryonic
      kidney (HEK)-293 cells coexpressing unedited human 5-HT(2CINI) receptors and
      Galpha(q) protein and in cultured mouse cortical neurons. Indicative of
      constitutive activity, the inverse agonist SB206,553 decreased basal inositol
      phosphate (IP) production in HEK-293 cells. The tetracyclic antidepressants
      mirtazapine and mianserin likewise suppressed basal IP formation. Conversely, the
      tricyclics amitriptyline and clomipramine, the m-chlorophenylpiperazine
      derivatives trazodone and nefazodone, and the 5-HT reuptake inhibitors fluoxetine
      and citalopram were inactive alone, although they blocked 5-HT-induced IP
      production. Inverse agonist actions of 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5
      tetrahydropyrrolo[2,3-f]indole (SB206,553) and mirtazapine were abolished by the
      neutral antagonist 6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy)pyridin-3
      ylcarbamoyl]indoline (SB242,084), which was inactive alone. As assessed by
      confocal microscopy and enzyme-linked immunosorbent assay, prolonged treatment of
      HEK-293 cells with SB206,553, mirtazapine, or mianserin, but not the other
      antidepressants, enhanced cell surface expression of 5-HT(2C) receptors: 5-HT
      induced IP production was also increased, and both these actions were blocked by
      SB242,084. Cortical neurons were shown by reverse transcription-polymerase chain
      reaction to predominantly express constitutively active 5-HT(2C) receptor
      isoforms. Prolonged pretreatment with SB206,553 or mirtazapine triggered an
      otherwise absent 5-HT-induced elevation in cytosolic Ca(2+) concentrations.
      SB242,084, which was inactive alone, abolished these effects of SB206,553 and
      mirtazapine. In conclusion, the tetracyclic antidepressants mirtazapine and
      mianserin, but not other clinically established antidepressants, suppress
      constitutive activity at recombinant and native 5-HT(2C) receptors. The clinical
      significance of inverse agonist versus neutral antagonist properties both during
      and after drug administration will be of interest to elucidate.

PMID- 18083779
TI  - Small-molecule screen identifies inhibitors of a human intestinal calcium
      activated chloride channel.
AB  - Calcium-activated chloride channels (CaCCs) are widely expressed in mammalian
      tissues, including intestinal epithelia, where they facilitate fluid secretion.
      Potent, selective CaCC inhibitors have not been available. We established a high
      throughput screen for identification of inhibitors of a human intestinal CaCC
      based on inhibition of ATP/carbachol-stimulated iodide influx in HT-29 cells
      after lentiviral infection with the yellow fluorescent halide-sensing protein YFP
      H148Q/I152L. Screening of 50,000 diverse, drug-like compounds yielded six classes
      of putative CaCC inhibitors, two of which, 3-acyl-2-aminothiophenes and 5-aryl-2
      aminothiazoles, inhibited by >95% iodide influx in HT-29 cells in response to
      multiple calcium-elevating agonists, including thapsigargin, without inhibition
      of calcium elevation, calcium-calmodulin kinase II activation, or cystic fibrosis
      transmembrane conductance regulator chloride channels. These compounds also
      inhibited calcium-dependent chloride secretion in T84 human intestinal epithelial
      cells. Patch-clamp analysis indicated inhibition of CaCC gating, which, together
      with the calcium-calmodulin data, suggests that the inhibitors target the CaCC
      directly. Structure-activity relationships were established from analysis of more
      than 1800 analogs, with IC(50) values of the best analogs down to approximately 1
      muM. Small-molecule CaCC inhibitors may be useful in pharmacological dissection
      of CaCC functions and in reducing intestinal fluid losses in CaCC-mediated
      secretory diarrheas.

PMID- 18083781
TI  - The effect of cyclooxygenase-2 inhibition on renal hemodynamic function in humans
      with type 1 diabetes.
AB  - OBJECTIVE: Studies in animal models suggest that cyclooxygenase-2 (COX2) plays a
      role in the regulation of the renal microcirculation in diabetes. Accordingly, we
      examined the role of COX2 in the control of renal hemodynamic function and in the
      renal response to hyperglycemia in humans with uncomplicated type 1 diabetes. We
      hypothesized that COX2 inhibition would alleviate the hyperfiltration state and
      would abrogate the hyperglycemia-mediated rise in glomerular filtration rate
      (GFR). RESEARCH DESIGN AND METHODS; Renal function was assessed during clamped
      euglycemia and hyperglycemia on 2 consecutive days before and then again after 14
      days of COX2 inhibition using 200 mg celecoxib once daily by mouth. For analysis,
      the cohort was then divided into two groups based on the baseline GFR: 9 subjects
      exhibited hyperfiltration (GFR >or=135 ml/min per 1.73 m(2)), and 12 subjects
      exhibited normofiltration (GFR <135 ml/min per 1.73 m(2)). RESULTS: Under
      euglycemic conditions, COX2 inhibition resulted in a significant decline in GFR
      in the hyperfiltration group (150 +/- 5 to 139 +/- 5 ml/min per 1.73 m(2)) but
      increased GFR in the normofiltration group (118 +/- 5 to 138 +/- 5 ml/min per
      1.73 m(2)). COX2 inhibition did not blunt the hyperglycemia-associated rise in
      GFR in the normofiltration group and was instead associated with an augmented
      rise in GFR. CONCLUSIONS: In summary, our results support the hypothesis that
      COX2 is an important determinant of renal hemodynamic function in subjects with
      type 1 diabetes. The renal response to COX2 inhibition emphasizes that
      hyperfiltration and normofiltration are distinct physiological states.

PMID- 18083782
TI  - Acute metformin therapy confers cardioprotection against myocardial infarction
      via AMPK-eNOS-mediated signaling.
AB  - OBJECTIVE: Clinical studies have reported that metformin reduces cardiovascular
      end points of type 2 diabetic subjects by actions that cannot solely be
      attributed to glucose-lowering effects. The therapeutic effects of metformin have
      been reported to be mediated by its activation of AMP-activated protein kinase
      (AMPK), a metabolite sensing protein kinase whose activation following myocardial
      ischemia has been suggested to be an endogenous protective signaling mechanism.
      We investigated the potential cardioprotective effects of a single, low-dose
      metformin treatment (i.e., 286-fold less than the maximum antihyperglycemic dose)
      in a murine model of myocardial ischemia-reperfusion (I/R) injury. RESEARCH
      DESIGN AND METHODS: Nondiabetic and diabetic (db/db) mice were subjected to
      transient myocardial ischemia for a period of 30 min followed by reperfusion.
      Metformin (125 microg/kg) or vehicle (saline) was administered either before
      ischemia or at the time of reperfusion. RESULTS: Administration of metformin
      before ischemia or at reperfusion decreased myocardial injury in both nondiabetic
      and diabetic mice. Importantly, metformin did not alter blood glucose levels.
      During early reperfusion, treatment with metformin augmented I/R-induced AMPK
      activation and significantly increased endothelial nitric oxide (eNOS)
      phosphorylation at residue serine 1177. CONCLUSIONS: These findings provide
      important information that myocardial AMPK activation by metformin following I/R
      sets into motion events, including eNOS activation, which ultimately lead to
      cardioprotection.

PMID- 18083783
TI  - Different brain responses to hypoglycemia induced by equipotent doses of the long
      acting insulin analog detemir and human regular insulin in humans.
AB  - OBJECTIVE: The acylated long-acting insulin analog detemir is more lipophilic
      than human insulin and likely crosses the blood-to-brain barrier more easily than
      does human insulin. The aim of these studies was to assess the brain/hypothalamus
      responses to euglycemia and hypoglycemia in humans during intravenous infusion of
      equipotent doses of detemir and human insulin. RESEARCH DESIGN AND METHODS: Ten
      normal, nondiabetic subjects (six men, age 36+/-7 years, and BMI 22.9+/-2.6
      kg/m(2)) were studied on four occasions at random during intravenous infusion of
      either detemir or human insulin in euglycemia (plasma glucose 90 mg/dl) or during
      stepped hypoglycemia (plasma glucose 90, 78, 66, 54, and 42 mg/dl steps).
      RESULTS: Plasma counterregulatory hormone response to hypoglycemia did not differ
      between detemir and human insulin. The glycemic thresholds for adrenergic
      symptoms were higher with detemir (51 +/- 7.7 mg/dl) versus human insulin (56 +/-
      7.8 mg/dl) (P = 0.029). However, maximal responses were greater with detemir
      versus human insulin for adrenergic (3 +/- 2.5 vs. 2.4 +/- 1.8) and
      neuroglycopenic (4 +/- 3.9 vs. 2.7+/-2.5) symptoms (score, P < 0.05). Glycemic
      thresholds for onset of cognitive dysfunction were lower with detemir versus
      human insulin (51 +/- 8.1 vs. 47 +/- 3.6 mg/dl, P = 0.031), and cognitive
      function was more deteriorated with detemir versus human insulin (P < 0.05).
      CONCLUSIONS: Compared with human insulin, responses to hypoglycemia with detemir
      resulted in higher glycemic thresholds for adrenergic symptoms and greater
      maximal responses for adrenergic and neuroglycopenic symptoms, with an earlier
      and greater impairment of cognitive function. Additional studies are needed to
      establish the effects of detemir on responses to hypoglycemia in subjects with
      diabetes.

PMID- 18083784
TI  - Increased skeletal muscle tumor necrosis factor-alpha and impaired insulin
      signaling persist in obese women with gestational diabetes mellitus 1 year
      postpartum.
AB  - OBJECTIVE: Women with gestational diabetes mellitus (GDM) demonstrate chronic and
      progressive insulin resistance and a markedly increased risk of converting to
      type 2 diabetes after pregnancy. However, the cellular mechanisms underlying this
      insulin resistance are unknown. RESEARCH DESIGN AND METHODS: We investigated the
      progression of insulin resistance in nine obese women with GDM during late
      pregnancy (30-36 weeks) and 1 year postpartum. Skeletal muscle biopsies were
      obtained at each visit, and insulin resistance was determined by the
      hyperinsulinemic-euglycemic clamp technique. RESULTS: Insulin resistance was not
      significantly improved in GDM women (4.1 +/- 0.4 vs. 5.8 +/- 1.1 10(-2) mg x kg
      FFM x min(-1)/microU x ml(-1)). Subjects did not experience significant weight
      loss postpartum. Body weight, fat mass, fasting glucose, and plasma tumor
      necrosis factor (TNF)-alpha remained higher 1 year postpartum than seen in
      previously studied normal glucose-tolerant women. Skeletal muscle TNF-alpha mRNA
      was elevated five- to sixfold in GDM women and remained higher 1 year postpartum.
      While levels of insulin receptor (IR), IR substrate (IRS)-1, and p85 alpha
      improved postpartum, insulin-stimulated IR tyrosine phosphorylation and receptor
      tyrosine kinase activity did not significantly improve postpartum in GDM. The
      levels of (312)Ser-IRS-1 also did not improve postpartum and correlated with TNF
      alpha mRNA (r(2) = 0.19, P < 0.03), consistent with a state of subclinical
      inflammation and chronic skeletal muscle insulin resistance. CONCLUSIONS: These
      results suggest the mechanisms underlying chronic insulin resistance in GDM women
      may be driven by increased inflammation that impinges on the IR and IRS-1
      signaling cascade in skeletal muscle. These findings have important implications
      for the health of GDM women during subsequent pregnancies and their risk for
      progression to type 2 diabetes.

PMID- 18083785
TI  - Targeting of RhoA/ROCK signaling ameliorates progression of diabetic nephropathy
      independent of glucose control.
AB  - OBJECTIVE: RhoA, a small GTPase protein, and its immediate downstream target, Rho
      kinase (ROCK), control a wide variety of signal transduction pathways. Recent
      studies have shown that fasudil, a selective ROCK inhibitor, may play a pivotal
      role in a number of pathological conditions, ranging from cardiovascular diseases
      to pulmonary hypertension and erectile dysfunction. Considerable evidence
      suggests that some of the beneficial effects of statins may also stem from their
      modulatory effects on RhoA/ROCK signaling. In the current study, we hypothesized
      that pharmacological blockade of the RhoA/ROCK pathway with either fasudil or
      simvastatin would ameliorate progression of diabetic nephropathy. RESEARCH DESIGN
      AND METHODS: In two separate experiments, diabetic db/db mice received fasudil
      (10 mg x kg(-) x day(-) i.p.) or simvastatin (40 mg x kg(-) x day(-) p.o.) for 16
      weeks. Untreated db/db and db/m mice served as controls. RESULTS: The kidney
      cortices of untreated db/db mice displayed increased ROCK activity compared with
      db/m mice. The fasudil-treated mice exhibited a significant reduction in ROCK
      activity, albuminuria, glomerular collagen IV accumulation, and urinary collagen
      IV excretion compared with untreated db/db mice. Interestingly, blood glucose was
      unaffected by fasudil administration. Treatment with simvastatin significantly
      attenuated RhoA activation in the kidney cortices of db/db mice and resulted in a
      significant reduction of albuminuria and mesangial matrix expansion. CONCLUSIONS:
      Based on these results, we propose that RhoA/ROCK blockade constitutes a novel
      approach to the treatment of diabetic nephropathy. Our data also suggest a
      critical role for RhoA/ROCK activation in the pathogenesis of diabetic
      nephropathy.

PMID- 18083786
TI  - Regulated beta-cell regeneration in the adult mouse pancreas.
AB  - Several studies have shown that the adult pancreas possesses a limited potential
      for beta-cell regeneration upon tissue injury. One of the difficulties in
      studying beta-cell regeneration has been the lack of a robust, synchronized
      animal model system that would allow controlled regulation of beta-cell loss and
      subsequent proliferation in adult pancreas. Here we present a transgenic mouse
      regeneration model in which the c-Myc transcription factor/mutant estrogen
      receptor (cMycER(TAM)) fusion protein can be specifically activated in mature
      beta-cells. We have studied these transgenic mice by immunohistochemical and
      biochemical methods to assess the ablation and posterior regeneration of beta
      cells. Activation of the cMycER(TAM) fusion protein results in synchronous and
      selective beta-cell apoptosis followed by the onset of acute diabetes.
      Inactivation of c-Myc leads to gradual regeneration of insulin-expressing cells
      and reversal of diabetes. Our results demonstrate that the mature pancreas has
      the ability to fully recover from almost complete ablation of all existing beta
      cells. Our results also suggest the regeneration of beta-cells is mediated by
      replication of beta-cells rather than neogenesis from pancreatic ducts.

PMID- 18083787
TI  - Delta down compared with delta pulse pressure as an indicator of volaemia during
      intracranial surgery.
AB  - BACKGROUND: Delta pulse pressure (DPP) and delta down (DD) are indicators of
      volaemia. The threshold value of DPP for discriminating between responders and
      non-responders to fluid loading (FL) is 13%. This study aimed at comparing DD
      with DPP during intracranial surgery. METHODS: Twenty-six adult patients
      undergoing scheduled intracranial surgery under general anaesthesia were
      enrolled. DD and DPP were simultaneously measured every 10 min. A DPP>13% on two
      consecutive occasions prompted a 250 ml FL. Pairs of data were analysed using
      regression analysis, receiver operating characteristics (ROC) curve, and
      prediction probability (Pk). RESULTS: We found a significant correlation between
      DD and DPP (R2=0.5431, P<0.001). ROC curve analysis revealed an excellent
      accuracy of DD in predicting a DPP value higher or lower than 13% (area under the
      curve: 0.967, se: 0.013). The DD threshold associated with the best sensitivity
      (0.90) and specificity (0.99) was 5 mm Hg. The Pk of DD to predict a DPP value
      higher or lower than 13% was 0.97 (se: 0.01). A total of 41 FL performed in 19
      patients resulted in a decrease of DD and DPP below 5 mm Hg and 13%,
      respectively, in all but one occasion. CONCLUSIONS: DD is as efficient as DPP to
      assess hypovolaemia and predict responsiveness to FL in patients undergoing
      intracranial surgery. A 5 mm Hg DD value can be considered as a valuable
      threshold for initiating FL. These results support its use during intracranial
      surgery.

PMID- 18083788
TI  - Time to insulin initiation cannot be used in defining latent autoimmune diabetes
      in adults.
AB  - OBJECTIVE: Latent autoimmune diabetes in adults is type 1 diabetes presenting as
      non-insulin dependent diabetes. One feature of the selection criteria is time
      independent of insulin treatment. We examine the validity of this criterion.
      RESEARCH DESIGN AND METHODS: Patients were recruited in nine European centers,
      and clinicians reported on criteria for initiating insulin. All patients were
      tested for GAD antibodies (GADAs) in a central laboratory. We examined time to
      insulin treatment for GADA-positive patients in six participating centers.
      RESULTS: There was intercenter variation in the criteria used to initiate
      insulin. Median time to insulin was 16.15 months (interqartile range 6.7-25.5) in
      centers with GADA testing compared with 45.6 months (29.5-61.8) in centers
      without routine GADA testing (P < 0.002). CONCLUSION: Time to insulin should not
      be used to define patients with LADA because it is dependent on local clinical
      judgment and the use of laboratory tests for GADA.

PMID- 18083789
TI  - Similarity of the impact of type 1 and type 2 diabetes on cardiovascular
      mortality in middle-aged subjects.
AB  - OBJECTIVE: To compare the risk of cardiovascular disease (CVD) death and the
      impact of hyperglycemia on the risk of CVD mortality associated with type 1
      diabetes to that associated with type 2 diabetes. RESEARCH DESIGN AND METHODS:
      The study comprised 173 participants with type 1 diabetes, 834 participants with
      type 2 diabetes, and 1,294 nondiabetic participants, aged 45-64 years at baseline
      and free of CVD. The age of onset of diabetes was >30 years in both diabetic
      groups. RESULTS: During an 18-year follow-up, 86 participants with type 1
      diabetes, 567 participants with type 2 diabetes, and 252 nondiabetic participants
      died. CVD mortality rates per 1,000 person-years were 23.1 (95% CI 16.9-31.9) in
      type 1 diabetic, 35.3 (30.8-40.4) in type 2 diabetic, and 4.6 (3.8-5.7) in
      nondiabetic participants. Adjusted hazard ratios for CVD mortality in
      participants with type 1 diabetes versus no diabetes was 3.6 (95% CI 2.2-5.7) in
      men and 13.3 (6.9-22.5) in women and in participants with type 2 diabetes versus
      no diabetes 3.3 (2.5-4.5) in men and 10.1 (6.7-17.4) in women. An increment of 1
      unit (%) of GHb increased CVD mortality by 52.5% (95% CI 28.4-81.3) in type 1
      diabetic subjects and by 7.5% (4.3-10.8) in type 2 diabetic participants.
      CONCLUSIONS: The impact of type 1 and type 2 diabetes on CVD mortality was
      similar. The effect of increasing hyperglycemia on the risk of CVD mortality was
      more profound in type 1 than in type 2 diabetic subjects.

PMID- 18083790
TI  - Clinical predictors of disease progression and medication initiation in untreated
      patients with type 2 diabetes and A1C less than 7%.
AB  - OBJECTIVE: Many patients with early diabetes remain untreated. Our objectives
      were to identify clinical predictors of 1) worsening glycemic control and 2)
      medical treatment initiation in response to worsening glycemic control among
      patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We identified 5,804
      type 2 diabetic patients seen at least twice between June 2005 and June 2006
      within our 12-clinic primary care network. We examined predictors of diabetes
      progression (A1C >or=7% or initiation of hypoglycemic agent) over a 1-year follow
      up period in 705 patients who had A1C <7% and were not on glucose-lowering
      medications at baseline. In the 200 patients in this group who progressed, we
      examined predictors of medical therapy initiation. RESULTS: In multivariate
      analyses, baseline A1C (P < 0.0001), younger age (P = 0.04), and weight gain (P =
      0.03) were independent predictors of progression after adjusting for race, sex,
      and baseline HDL levels. Each decade of increasing age reduced the risk of
      progression by 15%. Each 1-lb increase in weight was associated with a 2%
      increased odds of progression. Likelihood of medication initiation among
      progressors decreased by 40% (P = 0.02) with every decade of age and decreased by
      2.3% (P = 0.02) with each 1-mg/dl decrease in LDL level from baseline after
      adjusting for race, sex, and weight change. CONCLUSIONS: Among untreated primary
      care patients with type 2 diabetes and A1C <7%, younger patients and those with
      weight gain were more likely to have diabetes progression and should be the focus
      of aggressive diabetes management.

PMID- 18083791
TI  - Osteoprotegerin, thiazolidinediones treatment, and silent myocardial ischemia in
      type 2 diabetic patients.

PMID- 18083792
TI  - Overweight Latino children and adolescents have marked endothelial dysfunction
      and subclinical vascular inflammation in association with excess body fat and
      insulin resistance.
AB  - OBJECTIVE: We measured plasma markers of endothelial dysfunction, vascular
      inflammation, and pro-coagulation in obese Hispanic/Latino children and
      adolescents with normal glucose tolerance and determined their relationship to
      body composition and indexes of glucose and lipid metabolism. RESEARCH DESIGN AND
      METHODS: A total of 38 lean or obese Hispanic children and adolescents (10-18
      years of age) were selected. The overweight group (n = 21) had a BMI >85th
      percentile for their age and sex, and the lean group (n = 17) had a BMI between
      the 25th and 50th percentiles. Studies included an oral glucose tolerance test,
      measurements of plasma glucose and lipids, several markers of endothelial
      function and inflammation, and determination of body composition by dual X-ray
      absorptiometry. RESULTS: The obese group had higher systolic blood pressure and
      plasma triglycerides and was more insulin resistant than the lean group. The
      obese group also had higher plasma soluble intercellular adhesion molecule (259.5
      +/- 60.0 vs. 223.2 +/- 47.5 ng/ml, P = 0.047), tumor necrosis factor-alpha (2.57
      +/- 1.1 vs. 1.74 +/- 0.6 pg/ml, P = 0.008), high-sensitivity C-reactive protein
      (2.0 vs. 0.13 mg/l, P < 0.0001), plasminogen-activated inhibitor-1 (47.0 +/- 35.7
      vs. 12.0 +/- 5.2 ng/ml, P < 0.0001), tissue plasminogen activator (6.1 +/- 1.9
      vs. 4.1 +/- 0.8 ng/ml, P = 0.001), and white blood cell count (6.9 vs. 5.3 x
      10(3), P = 0.031) and lower levels of adiponectin (8.7 +/- 3.3 vs. 12.6 +/- 5.2
      microg/ml, P = 0.022). No significant differences were observed for soluble
      vascular cell adhesion molecule or interleukin-6. CONCLUSIONS: Overweight
      Hispanic children and adolescents with normal glucose tolerance exhibit increased
      plasma markers of endothelial dysfunction and subclinical inflammation in
      association with obesity and insulin resistance. These abnormalities may
      predispose them to the development of type 2 diabetes and cardiovascular disease.

PMID- 18083793
TI  - Effect of aging on glucose homeostasis: accelerated deterioration of beta-cell
      function in individuals with impaired glucose tolerance.
AB  - OBJECTIVE: To examine the effect of aging on insulin secretion (first- and second
      phase insulin release) and insulin sensitivity in people with normal glucose
      tolerance (NGT) or impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS:
      First- and second-phase insulin secretion and insulin sensitivity were assessed
      in hyperglycemic clamp experiments in 266 individuals with NGT and 130
      individuals with IGT, ranging in age from approximately 20 to approximately 70
      years. Changes in beta-cell function were compared using the disposition index to
      adjust for differences in insulin sensitivity. RESULTS: As expected, both phases
      of insulin release and insulin sensitivity were reduced in individuals with IGT
      (all P < 0.01). Insulin sensitivity was not independently correlated with age in
      either group. In people with NGT, the disposition index for first- and second
      phase insulin release decreased similarly at a rate of approximately 0.7% per
      year. In people with IGT, the disposition indexes for first- and second-phase
      insulin release decreased at greater rates ( approximately 2.2 and 1.4% per year,
      P = 0.002 and 0.009, respectively, vs. NGT), with the decrease in first phase
      being greater than that of second phase (P = 0.025). CONCLUSIONS: Insulin
      secretion (both first and second phase) normally decreases at a rate of
      approximately 0.7% per year with aging; this decrease in beta-cell function is
      accelerated about two-fold in people with impaired glucose tolerance-first phase
      to a greater extent than second phase. Finally, aging per se has no effect on
      insulin sensitivity independent of changes in body composition.

PMID- 18083794
TI  - Cognitive function in children and subsequent type 2 diabetes.
AB  - OBJECTIVE: To assess whether a diagnosis of type 2 diabetes by age 42 years is
      associated with prior cognitive deficits in childhood. RESEARCH DESIGN AND
      METHODS: Logistic regression estimated type 2 diabetes risk among 9,113 members
      of the 1958 British birth cohort of the National Child Development Study (NCDS).
      Associations with type 2 diabetes were estimated for general ability and reading
      comprehension assessments at age 11 years, modeled using SD units. Adjustment was
      for markers of early-life exposures, social and material family characteristics,
      sex, and disability, with further adjustment for BMI at age 7 years. RESULTS:
      Adjusted odds ratios (95% CIs) for type 2 diabetes (n = 69) are 0.67 (0.51-0.87)
      for general ability and 0.58 (0.44-0.77) for reading comprehension. Neither
      additional adjustment for BMI, nor limiting the definition of type 2 diabetes to
      onset after age 33 years altered the associations substantially. CONCLUSIONS:
      Impaired cognitive function may precede clinical onset of type 2 diabetes.

PMID- 18083795
TI  - Molecular dissection of variation in carbohydrate metabolism related to water
      soluble carbohydrate accumulation in stems of wheat.
AB  - Water-soluble carbohydrates (WSCs; composed of mainly fructans, sucrose [Suc],
      glucose [Glc], and fructose) deposited in wheat (Triticum aestivum) stems are
      important carbon sources for grain filling. Variation in stem WSC concentrations
      among wheat genotypes is one of the genetic factors influencing grain weight and
      yield under water-limited environments. Here, we describe the molecular
      dissection of carbohydrate metabolism in stems, at the WSC accumulation phase, of
      recombinant inbred Seri/Babax lines of wheat differing in stem WSC
      concentrations. Affymetrix GeneChip analysis of carbohydrate metabolic enzymes
      revealed that the mRNA levels of two fructan synthetic enzyme families (Suc:Suc 1
      fructosyltransferase and Suc:fructan 6-fructosyltransferase) in the stem were
      positively correlated with stem WSC and fructan concentrations, whereas the mRNA
      levels of enzyme families involved in Suc hydrolysis (Suc synthase and soluble
      acid invertase) were inversely correlated with WSC concentrations. Differential
      regulation of the mRNA levels of these Suc hydrolytic enzymes in Seri/Babax lines
      resulted in genotypic differences in these enzyme activities. Down-regulation of
      Suc synthase and soluble acid invertase in high WSC lines was accompanied by
      significant decreases in the mRNA levels of enzyme families related to sugar
      catabolic pathways (fructokinase and mitochondrion pyruvate dehydrogenase
      complex) and enzyme families involved in diverting UDP-Glc to cell wall synthesis
      (UDP-Glc 6-dehydrogenase, UDP-glucuronate decarboxylase, and cellulose synthase),
      resulting in a reduction in cell wall polysaccharide contents (mainly
      hemicellulose) in the stem of high WSC lines. These data suggest that
      differential carbon partitioning in the wheat stem is one mechanism that
      contributes to genotypic variation in WSC accumulation.

PMID- 18083796
TI  - Sucrose transporter StSUT4 from potato affects flowering, tuberization, and shade
      avoidance response.
AB  - Sucrose (Suc) transporters belong to a large gene family. The physiological role
      of SUT1 proteins has been intensively investigated in higher plants, whereas that
      of SUT4 proteins is so far unknown. All three known Suc transporters from potato
      (Solanum tuberosum), SUT1, SUT2, and SUT4, are colocalized and their RNA levels
      not only follow a diurnal rhythm, but also oscillate in constant light. Here, we
      examined the physiological effects of transgenic potato plants on RNA
      interference (RNAi)-inactivated StSUT4 expression. The phenotype of StSUT4-RNAi
      plants includes early flowering, higher tuber production, and reduced sensitivity
      toward light enriched in far-red wavelength (i.e. in canopy shade). Inhibition of
      StSUT4 led to tuber production of the strict photoperiodic potato subsp. andigena
      even under noninductive long-day conditions. Accumulation of soluble sugars and
      Suc efflux from leaves of transgenic plants are modified in StSUT4-RNAi plants,
      leading to modified Suc levels in sink organs. StSUT4 expression of wild-type
      plants is induced by gibberellins and ethephon, and external supply of
      gibberellic acid leads to even more pronounced differences between wild-type and
      StSUT4-RNAi plants regarding tuber yield and internode elongation, indicating a
      reciprocal regulation of StSUT4 and gibberellins.

PMID- 18083797
TI  - Cell wall polysaccharides are specifically involved in the exclusion of aluminum
      from the rice root apex.
AB  - Rice (Oryza sativa) is the most aluminum (Al)-resistant crop species among the
      small-grain cereals, but the mechanisms responsible for this trait are still
      unclear. Using two rice cultivars differing in Al resistance, rice sp. japonica
      'Nipponbare' (an Al-resistant cultivar) and rice sp. indica 'Zhefu802' (an Al
      sensitive cultivar), it was found that Al content in the root apex (0-10 mm) was
      significantly lower in Al-resistant 'Nipponbare' than in sensitive 'Zhefu802',
      with more of the Al localized to cell walls in 'Zhefu802', indicating that an Al
      exclusion mechanism is operating in 'Nipponbare'. However, neither organic acid
      efflux nor changes in rhizosphere pH appear to be responsible for the Al
      exclusion. Interestingly, cell wall polysaccharides (pectin, hemicellulose 1, and
      hemicellulose 2) in the root apex were found to be significantly higher in
      'Zhefu802' than in 'Nipponbare' in the absence of Al, and Al exposure increased
      root apex hemicellulose content more significantly in 'Zhefu802'. Root tip cell
      wall pectin methylesterase (PME) activity was constitutively higher in 'Zhefu802'
      than in 'Nipponbare', although Al treatment resulted in increased PME activity in
      both cultivars. Immunolocalization of pectins showed a higher proportion of
      demethylated pectins in 'Zhefu802', indicating a higher proportion of free pectic
      acid residues in the cell walls of 'Zhefu802' root tips. Al adsorption and
      desorption kinetics of root tip cell walls also indicated that more Al was
      adsorbed and bound Al was retained more tightly in 'Zhefu802', which was
      consistent with Al content, PME activity, and pectin demethylesterification
      results. These responses were specific to Al compared with other metals (CdCl(2),
      LaCl(3), and CuCl(2)), and the ability of the cell wall to adsorb these metals
      was also not related to levels of cell wall pectins. All of these results suggest
      that cell wall polysaccharides may play an important role in excluding Al
      specifically from the rice root apex.

PMID- 18083798
TI  - The Arabidopsis AtOPT3 protein functions in metal homeostasis and movement of
      iron to developing seeds.
AB  - The Arabidopsis thaliana AtOPT3 belongs to the oligopeptide transporter (OPT)
      family, a relatively poorly characterized family of peptide/modified peptide
      transporters found in archebacteria, bacteria, fungi, and plants. A null mutation
      in AtOPT3 resulted in embryo lethality, indicating an essential role for AtOPT3
      in embryo development. In this article, we report on the isolation and phenotypic
      characterization of a second AtOPT3 mutant line, opt3-2, harboring a T-DNA
      insertion in the 5' untranslated region of AtOPT3. The T-DNA insertion in the
      AtOPT3 promoter resulted in reduced but sufficient AtOPT3 expression to allow
      embryo formation in opt3-2 homozygous seeds. Phenotypic analyses of opt3-2 plants
      revealed three interesting loss-of-function phenotypes associated with iron
      metabolism. First, reduced AtOPT3 expression in opt3-2 plants resulted in the
      constitutive expression of root iron deficiency responses regardless of exogenous
      iron supply. Second, deregulation of root iron uptake processes in opt3-2 roots
      resulted in the accumulation of very high levels of iron in opt3-2 tissues.
      Hyperaccumulation of iron in opt3-2 resulted in the formation of brown necrotic
      areas in opt3-2 leaves and was more pronounced during the seed-filling stage.
      Third, reduced AtOPT3 expression resulted in decreased accumulation of iron in
      opt3-2 seeds. The reduced accumulation of iron in opt3-2 seeds is especially
      noteworthy considering the excessively high levels of accumulated iron in other
      opt3-2 tissues. AtOPT3, therefore, plays a critical role in two important aspects
      of iron metabolism, namely, maintenance of whole-plant iron homeostasis and iron
      nutrition of developing seeds.

PMID- 18083799
TI  - Interstrain gene transfer in Chlamydia trachomatis in vitro: mechanism and
      significance.
AB  - The high frequency of between-strain genetic recombinants of Chlamydia
      trachomatis among isolates obtained from human sexually transmitted infections
      suggests that lateral gene transfer (LGT) is an important means by which C.
      trachomatis generates variants that have enhanced relative fitness. A mechanism
      for LGT in C. trachomatis has not been described, and investigation of this
      phenomenon by experimentation has been hampered by the obligate intracellular
      development of this pathogen. We describe here experiments that readily detected
      LGT between strains of C. trachomatis in vitro. Host cells were simultaneously
      infected with an ofloxacin-resistant (Ofx(r)) mutant of a serovar L1 strain
      (L1:Ofx(r)-1) and a rifampin-resistant (Rif(r)) mutant of a serovar D strain
      (D:Rif(r)-1). Development occurred in the absence of antibiotics, and the progeny
      were subjected to selection for Ofx(r) Rif(r) recombinants. The parental strains
      differed at many polymorphic nucleotide sites, and DNA sequencing was used to map
      genetic crossovers and to determine the parental sources of DNA segments in 14
      recombinants. Depending on the assumed DNA donor, the estimated minimal length of
      the transferred DNA was > or = 123 kb in one recombinant but was > or = 336 to >
      or = 790 kb in all other recombinants. Such trans-DNA lengths have been
      associated only with conjugation in known microbial LGT systems, but natural DNA
      transformation remains a conceivable mechanism. LGT studies can now be performed
      with diverse combinations of C. trachomatis strains, and they could have
      evolutionary interest and yield useful recombinants for functional analysis of
      allelic differences between strains.

PMID- 18083800
TI  - Limiting too much of a good thing: a negative feedback mechanism prevents
      unregulated translocation of type III effector proteins.

PMID- 18083801
TI  - Molecular characterization reveals similar virulence gene content in unrelated
      clonal groups of Escherichia coli of serogroup O174 (OX3).
AB  - Most severe illnesses that are attributed to Shiga toxin-producing Escherichia
      coli are caused by isolates that also carry a pathogenicity island called the
      locus of enterocyte effacement (LEE). However, many cases of severe disease are
      associated with LEE-negative strains. We characterized the virulence gene content
      and the evolutionary relationships of Escherichia coli isolates of serogroup O174
      (formerly OX3), strains of which have been implicated in cases of hemorrhagic
      colitis and hemolytic uremic syndrome. A total of 56 isolates from humans, farm
      animals, and food were subjected to multilocus virulence gene profiling (MVGP),
      and a subset of 16 isolates was subjected to multilocus sequence analysis (MLSA).
      The MLSA revealed that the O174 isolates fall into four separate evolutionary
      clusters within the E. coli phylogeny and are related to a diverse array of
      clonal groups, including enteropathogenic E. coli 2 (EPEC 2), enterohemorrhagic
      E. coli 2 (EHEC 2), and EHEC-O121. Of the 15 genes that we surveyed with MVGP,
      only 6 are common in the O174 strains. The different clonal groups within the
      O174 serogroup appear to have independently acquired and maintained similar sets
      of genes that include the Shiga toxins (stx1 and stx2) and two adhesins (saa and
      iha). The absence of certain O island (OI) genes, such as those found on OI-122,
      is consistent with the notion that certain pathogenicity islands act
      cooperatively with the LEE island.

PMID- 18083802
TI  - Escherichia coli cytosolic glycerophosphodiester phosphodiesterase (UgpQ)
      requires Mg2+, Co2+, or Mn2+ for its enzyme activity.
AB  - Escherichia coli cytosolic glycerophosphodiester phosphodiesterase, UgpQ,
      functions in the absence of other proteins encoded by the ugp operon and requires
      Mg2+, Mn2+, or Co2+, in contrast to Ca2+-dependent periplasmic
      glycerophosphodiester phosphodiesterase, GlpQ. UgpQ has broad substrate
      specificity toward various glycerophosphodiesters, producing sn-glycerol-3
      phosphate and the corresponding alcohols. UgpQ accumulates under conditions of
      phosphate starvation, suggesting that it allows the utilization of
      glycerophosphodiesters as a source of phosphate. These results clarify how E.
      coli utilizes glycerophosphodiesters using two homologous enzymes, UgpQ and GlpQ.

PMID- 18083803
TI  - Tn5 synaptic complex formation: role of transposase residue W450.
AB  - A series of Tn5 transposases (Tnp's) with mutations at the conserved amino acid
      position W450, which was structurally predicted to be important for synapsis,
      have been generated and characterized. This study demonstrates that W450 is
      involved in hydrophobic (and possibly aromatic) contacts within the Tnp monomer
      that negatively regulate synaptic complex formation.

PMID- 18083804
TI  - Affinity isolation and I-DIRT mass spectrometric analysis of the Escherichia coli
      O157:H7 Sakai RNA polymerase complex.
AB  - Bacteria contain a single multisubunit RNA polymerase that is responsible for the
      synthesis of all RNA. Previous studies of the Escherichia coli K-12 laboratory
      strain identified a group of effector proteins that interact directly with RNA
      polymerase to modulate the efficiency of transcription initiation, elongation, or
      termination. Here we used a rapid affinity isolation technique to isolate RNA
      polymerase from the pathogenic Escherichia coli strain O157:H7 Sakai. We analyzed
      the RNA polymerase enzyme complex using mass spectrometry and identified
      associated proteins. Although E. coli O157:H7 Sakai contains more than 1,600
      genes not present in the K-12 strain, many of which are predicted to be involved
      in transcription regulation, all of the identified proteins in this study were
      encoded on the "core" E. coli genome.

PMID- 18083805
TI  - Pseudo-B12 joins the cofactor family.

PMID- 18083806
TI  - Interaction of CheY with the C-terminal peptide of CheZ.
AB  - Chemotaxis, a means for motile bacteria to sense the environment and achieve
      directed swimming, is controlled by flagellar rotation. The primary output of the
      chemotaxis machinery is the phosphorylated form of the response regulator CheY (P
      CheY). The steady-state level of P-CheY dictates the direction of rotation of the
      flagellar motor. The chemotaxis signal in the form of P-CheY is terminated by the
      phosphatase CheZ. Efficient dephosphorylation of CheY by CheZ requires two
      distinct protein-protein interfaces: one involving the strongly conserved C
      terminal helix of CheZ (CheZ(C)) tethering the two proteins together and the
      other constituting an active site for catalytic dephosphorylation. In a previous
      work (J. Guhaniyogi, V. L. Robinson, and A. M. Stock, J. Mol. Biol. 359:624-645,
      2006), we presented high-resolution crystal structures of CheY in complex with
      the CheZ(C) peptide that revealed alternate binding modes subject to the
      conformational state of CheY. In this study, we report biochemical and structural
      data that support the alternate-binding-mode hypothesis and identify key
      recognition elements in the CheY-CheZ(C) interaction. In addition, we present
      kinetic studies of the CheZ(C)-associated effect on CheY phosphorylation with its
      physiologically relevant phosphodonor, the histidine kinase CheA. Our results
      indicate mechanistic differences in phosphotransfer from the kinase CheA versus
      that from small-molecule phosphodonors, explaining a modest twofold increase of
      CheY phosphorylation with the former, observed in this study, relative to a 10
      fold increase previously documented with the latter.

PMID- 18083807
TI  - Interaction between two putative glycosyltransferases is required for
      glycosylation of a serine-rich streptococcal adhesin.
AB  - Fap1, a serine-rich glycoprotein, is essential for fimbrial biogenesis and
      biofilm formation of Streptococcus parasanguinis (formerly S. parasanguis). Fap1
      like proteins are conserved in many streptococci and staphylococci and have been
      implicated in bacterial virulence. Fap1 contains two serine-rich repeat regions
      that are modified by O-linked glycosylation. A seven-gene cluster has been
      identified, and this cluster is implicated in Fap1 biogenesis. In this study, we
      investigated the initial step of Fap1 glycosylation by using a recombinant Fap1
      as a model. This recombinant molecule has the same monosaccharide composition
      profile as the native Fap1 protein. Glycosyl linkage analyses indicated that N
      acetylglucosamine (GlcNAc) is among the first group of sugar residues transferred
      to the Fap1 peptide. Two putative glycosyltransferases, Gtf1 and Gtf2, were
      essential for the glycosylation of Fap1 with GlcNAc-containing oligosaccharide(s)
      in both S. parasanguinis as well as in the Fap1 glycosylation system in
      Escherichia coli. Yeast two-hybrid analysis as well as in vitro and in vivo
      glutathione S-transferase pull-down assays demonstrated the two putative
      glycosyltransferases interacted with each other. The interaction domain was
      mapped to an N-terminal region of Gtf1 that was required for the Fap1
      glycosylation. The data in this study suggested that the formation of the Gtf1
      and Gtf2 complex was required for the initiation of the Fap1 glycosylation and
      that the N-terminal region of Gtf1 was necessary.

PMID- 18083808
TI  - Gamma-butyrolactone-dependent expression of the Streptomyces antibiotic
      regulatory protein gene srrY plays a central role in the regulatory cascade
      leading to lankacidin and lankamycin production in Streptomyces rochei.
AB  - Our previous studies revealed that the srrX and srrA genes carried on the large
      linear plasmid pSLA2-L constitute a gamma-butyrolactone-receptor system in
      Streptomyces rochei. Extensive transcriptional analysis has now showed that the
      Streptomyces antibiotic regulatory protein gene srrY, which is also carried on
      pSLA2-L, is a target of the receptor/repressor SrrA and plays a central role in
      lankacidin and lankamycin production. The srrY gene was expressed in a growth
      dependent manner, slightly preceding antibiotic production. The expression of
      srrY was undetectable in the srrX mutant but was restored in the srrX srrA double
      mutant. In addition, SrrA was bound specifically to the promoter region of srrY,
      and this binding was prevented by the addition of the S. rochei gamma
      butyrolactone fraction, while the W119A mutant receptor SrrA was kept bound even
      in the presence of S. rochei gamma-butyrolactone. Furthermore, the introduction
      of an intact srrY gene under the control of a foreign promoter into the srrX or
      srrA(W119A) mutant restored antibiotic production. All of these results confirmed
      the signaling pathway from srrX through srrA to srrY, leading to lankacidin and
      lankamycin production.

PMID- 18083809
TI  - Gene acquisition at the insertion site for SCCmec, the genomic island conferring
      methicillin resistance in Staphylococcus aureus.
AB  - Staphylococcus aureus becomes resistant to methicillin by acquiring a genomic
      island, known as staphylococcal chromosome cassette mec (SCCmec), which contains
      the methicillin resistance determinant, mecA. SCCmec is site-specifically
      integrated into the staphylococcal chromosome at a locus known as the SCCmec
      attachment site (attB). In an effort to gain a better understanding of the
      potential that methicillin-sensitive S. aureus (MSSA) isolates have for acquiring
      SCCmec, the nucleotide sequences of attB and surrounding DNA regions were
      examined in a diverse collection of 42 MSSA isolates. The chromosomal region
      surrounding attB varied among the isolates studied and appears to be a common
      insertion point for acquired foreign DNA. Insertions of up to 15.1 kb were found
      containing open reading frames with homology to enterotoxin genes, restriction
      modification systems, transposases, and several sequences that have not been
      previously described in staphylococci. Two groups, containing eight and four
      isolates, had sequences found in known SCCmec elements, suggesting SCCmec
      elements may have evolved through repeated DNA insertions at this locus. In
      addition, the attB sequences of the majority of MSSA isolates in this collection
      differ from the attB sequences of strains for which integrase-mediated SCCmec
      insertion or excision has been demonstrated, suggesting that some S. aureus
      isolates may lack the ability to site-specifically integrate SCCmec into their
      chromosomes.

PMID- 18083810
TI  - A combination of sbmA and tolC mutations in Escherichia coli K-12 Tn10-carrying
      strains results in hypersusceptibility to tetracycline.
AB  - Previously, we demonstrated that Escherichia coli tolC mutations reduce the high
      level resistance to tetracycline afforded by the transposon Tn10-encoded TetA
      pump from resistance at 200 microg/ml to resistance at 40 microg/ml. In this
      study, we found that the addition of an sbmA mutation to a tolC::Tn10 mutant
      exacerbates this phenotype: the double mutant did not form colonies, even in the
      presence of tetracycline at a concentration as low as 5 microg/ml. Inactivation
      of sbmA alone partially inhibited high-level tetracycline resistance, from
      resistance at 200 microg/ml to resistance at 120 microg/ml. There thus appears to
      be an additive effect of the mutations, resulting in almost complete suppression
      of the phenotypic expression of Tn10 tetracycline resistance.

PMID- 18083811
TI  - Differential regulation of high-affinity phosphate transport systems of
      Mycobacterium smegmatis: identification of PhnF, a repressor of the phnDCE
      operon.
AB  - The uptake of phosphate into the cell via high-affinity, phosphate-specific
      transport systems has been studied with several species of mycobacteria. All of
      these species have been shown to contain several copies of such transport
      systems, which are synthesized in response to phosphate limitation. However, the
      mechanisms leading to the expression of the genes encoding these transporters
      have not been studied. This study reports on the investigation of the regulation
      of the pstSCAB and the phnDCE operons of Mycobacterium smegmatis. The phn locus
      contains an additional gene, phnF, encoding a GntR-like transcriptional
      regulator. Expression analyses of a phnF deletion mutant demonstrated that PhnF
      acts as a repressor of the phnDCE operon but does not affect the expression of
      pstSCAB. The deletion of pstS, which is thought to cause the constitutive
      expression of genes regulated by the two-component system SenX3-RegX3, led to the
      constitutive expression of the transcriptional fusions pstS-lacZ, phnD-lacZ, and
      phnF-lacZ, suggesting that phnDCE and phnF are conceivably new members of the
      SenX3-RegX3 regulon of M. smegmatis. Two presumptive binding sites for PhnF in
      the intergenic region between phnD and phnF were identified and shown to be
      required for the repression of phnD and phnF, respectively. We propose a model in
      which the transcription of pstSCAB is controlled by the two-component SenX3-RegX3
      system, while phnDCE and phnF are subject to dual control by SenX3-RegX3 and
      PhnF.

PMID- 18083812
TI  - Pseudomonas aeruginosa PqsA is an anthranilate-coenzyme A ligase.
AB  - Pseudomonas aeruginosa is an opportunistic human pathogen which relies on several
      intercellular signaling systems for optimum population density-dependent
      regulation of virulence genes. The Pseudomonas quinolone signal (PQS) is a 3
      hydroxy-4-quinolone with a 2-alkyl substitution which is synthesized by the
      condensation of anthranilic acid with a 3-keto-fatty acid. The pqsABCDE operon
      has been identified as being necessary for PQS production, and the pqsA gene
      encodes a predicted protein with homology to acyl coenzyme A (acyl-CoA) ligases.
      In order to elucidate the first step of the 4-quinolone synthesis pathway in P.
      aeruginosa, we have characterized the function of the pqsA gene product. Extracts
      prepared from Escherichia coli expressing PqsA were shown to catalyze the
      formation of anthraniloyl-CoA from anthranilate, ATP, and CoA. The PqsA protein
      was purified as a recombinant His-tagged polypeptide, and this protein was shown
      to have anthranilate-CoA ligase activity. The enzyme was active on a variety of
      aromatic substrates, including benzoate and chloro and fluoro derivatives of
      anthranilate. Inhibition of PQS formation in vivo was observed for the chloro-
      and fluoroanthranilate derivatives, as well as for several analogs which were not
      PqsA enzymatic substrates. These results indicate that the PqsA protein is
      responsible for priming anthranilate for entry into the PQS biosynthetic pathway
      and that this enzyme may serve as a useful in vitro indicator for potential
      agents to disrupt quinolone signaling in P. aeruginosa.

PMID- 18083813
TI  - Genetics for Pseudoalteromonas provides tools to manipulate marine bacterial
      virus PM2.
AB  - The genetic manipulation of marine double-stranded DNA (dsDNA) bacteriophage PM2
      (Corticoviridae) has been limited so far. The isolation of an autonomously
      replicating DNA element of Pseudoalteromonas haloplanktis TAC125 and construction
      of a shuttle vector replicating in both Escherichia coli and Pseudoalteromonas
      enabled us to design a set of conjugative shuttle plasmids encoding tRNA
      suppressors for amber mutations. Using a host strain carrying a suppressor
      plasmid allows the introduction and analysis of nonsense mutations in PM2. Here,
      we describe the isolation and characterization of a suppressor-sensitive PM2 sus2
      mutant deficient in the structural protein P10. To infect and replicate, PM2
      delivers its 10-kbp genome across the cell envelopes of two gram-negative
      Pseudoalteromonas species. The events leading to the internalization of the
      circular supercoiled dsDNA are puzzling. In a poorly understood process that
      follows receptor recognition, the virion capsid disassembles and the internal
      membrane fuses with the host outer membrane. While beginning to unravel the
      mechanism of this process, we found that protein P10 plays an essential role in
      the host cell penetration.

PMID- 18083814
TI  - Genetic and biochemical analysis of CodY-binding sites in Bacillus subtilis.
AB  - CodY is a global transcriptional regulator that is known to control directly the
      expression of at least two dozen operons in Bacillus subtilis, but the rules that
      govern the binding of CodY to its target DNA have been unclear. Using DNase I
      footprinting experiments, we identified CodY-binding sites upstream of the B.
      subtilis ylmA and yurP genes. The protected regions overlapped versions of a
      previously proposed CodY-binding consensus motif, AATTTTCWGAAAATT. Multiple
      single mutations were introduced into the CodY-binding sites of the ylmA, yurP,
      dppA, and ilvB genes. The mutations affected both the affinity of CodY for its
      binding sites in vitro and the expression in vivo of lacZ fusions that carry
      these mutations in their promoter regions. Our results show that versions of the
      AATTTTCWGAAAATT motif, first identified for Lactococcus lactis CodY, with up to
      five mismatches play an important role in the interaction of B. subtilis CodY
      with DNA.

PMID- 18083815
TI  - Characterization of the SOS regulon of Caulobacter crescentus.
AB  - The SOS regulon is a paradigm of bacterial responses to DNA damage. A wide
      variety of bacterial species possess homologs of lexA and recA, the central
      players in the regulation of the SOS circuit. Nevertheless, the genes actually
      regulated by the SOS have been determined only experimentally in a few bacterial
      species. In this work, we describe 37 genes regulated in a LexA-dependent manner
      in the alphaproteobacterium Caulobacter crescentus. In agreement with previous
      results, we have found that the direct repeat GTTCN7GTTC is the SOS operator of
      C. crescentus, which was confirmed by site-directed mutagenesis studies of the
      imuA promoter. Several potential promoter regions containing the SOS operator
      were identified in the genome, and the expression of the corresponding genes was
      analyzed for both the wild type and the lexA strain, demonstrating that the vast
      majority of these genes are indeed SOS regulated. Interestingly, many of these
      genes encode proteins with unknown functions, revealing the potential of this
      approach for the discovery of novel genes involved in cellular responses to DNA
      damage in prokaryotes, and illustrating the diversity of SOS-regulated genes
      among different bacterial species.

PMID- 18083816
TI  - In vivo growth of Pseudomonas aeruginosa strains PAO1 and PA14 and the
      hypervirulent strain LESB58 in a rat model of chronic lung infection.
AB  - Pseudomonas aeruginosa chronic lung infections are the major cause of morbidity
      and mortality in cystic fibrosis (CF) patients. The P. aeruginosa strains PAO1
      and PA14 were compared with the Liverpool epidemic strain LESB58 to assess in
      vivo growth, infection kinetics, and bacterial persistence and localization
      within tissues in a rat model of chronic lung infection. The three P. aeruginosa
      strains demonstrated similar growth curves in vivo but differences in tissue
      distribution. The LESB58 strain persisted in the bronchial lumen, while the PAO1
      and PA14 strains were found localized in the alveolar regions and grew as
      macrocolonies after day 7 postinfection. Bacterial strains were compared for
      swimming and twitching motility and for the production of biofilm. The P.
      aeruginosa LESB58 strain produced more biofilm than PAO1 and PA14. Competitive
      index (CI) analysis of PAO1, PA14, and LESB58 in vivo indicated CI values of
      0.002, 0.0002, and 0.14 between PAO1-PA14, PAO1-LESB58, and LESB58-PA14,
      respectively. CI analysis comparing the in vivo growth of the PAO1 DeltaPA5441
      mutant and four PA14 surface attachment-defective (sad) mutants gave CI values 10
      to 1,000 times lower in competitions with their respective wild-type strains PAO1
      and PA14. P. aeruginosa strains studied in the rat model of chronic lung
      infection demonstrated similar in vivo growth but differences in virulence as
      shown with a competitive in vivo assay. These differences were further confirmed
      with biofilm and motility in vitro assays, where strain LESB58 produced more
      biofilm but had less capacity for motility than PAO1 and PA14.

PMID- 18083817
TI  - Role of the multidrug resistance regulator MarA in global regulation of the hdeAB
      acid resistance operon in Escherichia coli.
AB  - MarA, a transcriptional regulator in Escherichia coli, affects functions such as
      multiple-antibiotic resistance (Mar) and virulence. Usually an activator, MarA is
      a repressor of hdeAB and other acid resistance genes. We found that, in wild-type
      cells grown in LB medium at pH 7.0 or pH 5.5, repression of hdeAB by MarA
      occurred only in stationary phase and was reduced in the absence of H-NS and
      GadE, the main regulators of hdeAB. Moreover, repression of hdeAB by MarA was
      greater in the absence of GadX or Lrp in exponential phase at pH 7.0 and in the
      absence of GadW or RpoS in stationary phase at pH 5.5. In turn, MarA enhanced
      repression of hdeAB by H-NS and hindered activation by GadE in stationary phase
      and also reduced the activity of GadX, GadW, RpoS, and Lrp on hdeAB under some
      conditions. As a result of its direct and indirect effects, overexpression of
      MarA prevented most of the induction of hdeAB expression as cells entered
      stationary phase and made the cells sevenfold more sensitive to acid challenge at
      pH 2.5. These findings show that repression of hdeAB by MarA depends on pH,
      growth phase, and other regulators of hdeAB and is associated with reduced
      resistance to acid conditions.

PMID- 18083818
TI  - Characterization of a new rhamnogalacturonan acetyl esterase from Bacillus
      halodurans C-125 with a new putative carbohydrate binding domain.
AB  - BH1115 is a gene from Bacillus halodurans strain C-125 that hypothetically
      encodes a rhamnogalacturonan acetyl esterase (RGAE) of the CE-12 family. As
      confirmation, this gene was cloned, and the product was expressed in Escherichia
      coli strain Rosetta (DE3) cells and purified. The enzyme obtained was monomeric,
      with a molecular mass of 45 kDa, and exhibited alkaliphilic properties. A study
      of the inhibition of the activity by some modulators confirmed that the catalytic
      triad for the esterase activity was Ser-His-Asp. This enzyme also presents broad
      substrate specificity and is active toward 7-aminocephalosporanic acid,
      cephalosporin C, p-nitrophenyl acetate, beta-naphthyl acetate, glucose
      pentaacetate, and acetylated xylan. Moreover, RGAE from B. halodurans achieves a
      synergistic effect with xylanase A toward acetylated xylan. As a member of the
      SGNH family, it does not adopt the common alpha/beta hydrolase fold. The homology
      between the folds of RGAE from Aspergillus aculeatus and the hypothetical YxiM
      precursor from Bacillus subtilis, which both belong to the SGNH family,
      illustrates the divergence of such proteins from a common ancestor. Furthermore,
      the enzyme possesses a putative substrate binding region at the N terminus of the
      protein which has never been described to date for any RGAE.

PMID- 18083819
TI  - A mutational analysis defines Vibrio fischeri LuxR binding sites.
AB  - Vibrio fischeri quorum sensing involves the LuxI and LuxR proteins. The LuxI
      protein generates the quorum-sensing signal N-3-oxohexanoyl-l-homoserine lactone
      (3OC6-HSL), and LuxR is a signal-responsive transcriptional regulator which
      activates the luminescence (lux) genes and 17 other V. fischeri genes. For
      activation of the lux genes, LuxR binds to a 20-base-pair inverted repeat, the
      lux box, which is centered 42.5 base pairs upstream of the transcriptional start
      of the lux operon. Similar lux box-like elements have been identified in only a
      few of the LuxR-activated V. fischeri promoters. To better understand the DNA
      sequence elements required for LuxR binding and to identify binding sites in LuxR
      regulated promoters other than the lux operon promoter, we have systematically
      mutagenized the lux box and evaluated the activity of many mutants. By doing so,
      we have identified nucleotides that are critical for promoter activity.
      Interestingly, certain lux box mutations allow a 3OC6-HSL-independent LuxR
      activation of the lux operon promoter. We have used the results of the mutational
      analysis to create a consensus lux box, and we have used this consensus sequence
      to identify LuxR binding sites in 3OC6-HSL-activated genes for which lux boxes
      could not be identified previously.

PMID- 18083820
TI  - Clostridium perfringens spore germination: characterization of germinants and
      their receptors.
AB  - Clostridium perfringens food poisoning is caused by type A isolates carrying a
      chromosomal enterotoxin (cpe) gene (C-cpe), while C. perfringens-associated non
      food-borne gastrointestinal (GI) diseases are caused by isolates carrying a
      plasmid-borne cpe gene (P-cpe). C. perfringens spores are thought to be the
      important infectious cell morphotype, and after inoculation into a suitable host,
      these spores must germinate and return to active growth to cause GI disease. We
      have found differences in the germination of spores of C-cpe and P-cpe isolates
      in that (i) while a mixture of L-asparagine and KCl was a good germinant for
      spores of C-cpe and P-cpe isolates, KCl and, to a lesser extent, L-asparagine
      triggered spore germination in C-cpe isolates only; and (ii) L-alanine or L
      valine induced significant germination of spores of P-cpe but not C-cpe isolates.
      Spores of a gerK mutant of a C-cpe isolate in which two of the proteins of a
      spore nutrient germinant receptor were absent germinated slower than wild-type
      spores with KCl, did not germinate with L-asparagine, and germinated poorly
      compared to wild-type spores with the nonnutrient germinants dodecylamine and a
      1:1 chelate of Ca2+ and dipicolinic acid. In contrast, spores of a gerAA mutant
      of a C-cpe isolate that lacked another component of a nutrient germinant receptor
      germinated at the same rate as that of wild-type spores with high concentrations
      of KCl, although they germinated slightly slower with a lower KCl concentration,
      suggesting an auxiliary role for GerAA in C. perfringens spore germination. In
      sum, this study identified nutrient germinants for spores of both C-cpe and P-cpe
      isolates of C. perfringens and provided evidence that proteins encoded by the
      gerK operon are required for both nutrient-induced and non-nutrient-induced spore
      germination.

PMID- 18083821
TI  - Xylanase attachment to the cell wall of the hyperthermophilic bacterium
      Thermotoga maritima.
AB  - The cellular localization and processing of the endo-xylanases (1,4-beta-D-xylan
      xylanohydrolase; EC 3.2.1.8) of the hyperthermophile Thermotoga maritima were
      investigated, in particular with respect to the unusual outer membrane ("toga")
      of this gram-negative bacterium. XynB (40 kDa) was detected in the periplasmic
      fraction of T. maritima cells and in the culture supernatant. XynA (120 kDa) was
      partially released to the surrounding medium, but most XynA remained cell
      associated. Immunogold labeling of thin sections revealed that cell-bound XynA
      was localized mainly in the outer membranes of T. maritima cells. Amino-terminal
      sequencing of purified membrane-bound XynA revealed processing of the signal
      peptide after the eighth residue, thereby leaving the hydrophobic core of the
      signal peptide attached to the enzyme. This mode of processing is reminiscent of
      type IV prepilin signal peptide cleavage. Removal of the entire XynA signal
      peptide was necessary for release from the cell because enzyme purified from the
      culture supernatant lacked 44 residues at the N terminus, including the
      hydrophobic part of the signal peptide. We conclude that toga association of XynA
      is mediated by residues 9 to 44 of the signal peptide. The biochemical and
      electron microscopic localization studies together with the amino-terminal
      processing data indicate that XynA is held at the cell surface of T. maritima via
      a hydrophobic peptide anchor, which is highly unusual for an outer membrane
      protein.

PMID- 18083822
TI  - Characterization of the sequence specificity determinants required for processing
      and control of sex pheromone by the intramembrane protease Eep and the plasmid
      encoded protein PrgY.
AB  - Conjugative transfer of the Enterococcus faecalis plasmid pCF10 is induced by the
      peptide pheromone cCF10 when recipient-produced cCF10 is detected by donors.
      cCF10 is produced by proteolytic processing of the signal sequence of a
      chromosomally encoded lipoprotein (CcfA). In donors, endogenously produced cCF10
      is carefully controlled to prevent constitutive expression of conjugation
      functions, an energetically wasteful process, except in vivo, where endogenous
      cCF10 induces a conjugation-linked virulence factor. Endogenous cCF10 is
      controlled by two plasmid-encoded products; a membrane protein PrgY reduces
      pheromone levels in donors, and a secreted inhibitor peptide iCF10 inhibits the
      residual endogenous pheromone that escapes PrgY control. In this study we
      genetically determined the amino acid specificity determinants within PrgY,
      cCF10, and the cCF10 precursor that are necessary for cCF10 processing and for
      PrgY-mediated control. We showed that amino acid residues 125 to 241 of PrgY are
      required for specific recognition of cCF10 and that PrgY recognizes determinants
      within the heptapeptide cCF10 sequence, supporting a direct interaction between
      PrgY and mature cCF10. In addition, we found that a regulated intramembrane
      proteolysis (RIP) family pheromone precursor-processing protein Eep recognizes
      amino acids N-terminal to cCF10 in the signal sequence of CcfA. These results
      support a model where Eep directly targets pheromone precursors for RIP and PrgY
      interacts directly with the mature cCF10 peptide during processing. Despite
      evidence that both PrgY and Eep associate with cCF10 in or near the membrane,
      results presented here indicate that these two proteins function independently.

PMID- 18083823
TI  - The acyl-homoserine lactone-type quorum-sensing system modulates cell motility
      and virulence of Erwinia chrysanthemi pv. zeae.
AB  - Erwinia chrysanthemi pv. zeae is one of the Erwinia chrysanthemi pathovars that
      infects on both dicotyledons and monocotyledons. However, little is known about
      the molecular basis and regulatory mechanisms of its virulence. By using a
      transposon mutagenesis approach, we cloned the genes coding for an E.
      chrysanthemi pv. zeae synthase of acyl-homoserine lactone (AHL) quorum-sensing
      signals (expI(Ecz)) and a cognate response regulator (expR(Ecz)). Chromatography
      analysis showed that expI(Ecz) encoded production of the AHL signal N-(3-oxo
      hexanoyl)-homoserine lactone (OHHL). Null mutation of expI(Ecz) in the E.
      chrysanthemi pv. zeae strain EC1 abolished AHL production, increased bacterial
      swimming and swarming motility, disabled formation of multicell aggregates, and
      attenuated virulence of the pathogen on potato tubers. The mutation also
      marginally reduced the inhibitory activity of E. chrysanthemi pv. zeae on rice
      seed germination. The mutant phenotypes were rescued by either exogenous addition
      of AHL signal or in trans expression of expI(Ecz). These data demonstrate that
      the AHL-type QS signal plays an essential role in modulation of E. chrysanthemi
      pv. zeae cell motility and the ability to form multicell aggregates and is
      involved in regulation of bacterial virulence.

PMID- 18083824
TI  - Candida albicans Als adhesins have conserved amyloid-forming sequences.
AB  - The cell wall-bound Als adhesins of Candida albicans mediate both yeast-to-host
      tissue adherence and yeast aggregation. This aggregation is amyloid-like, with
      self-propagating secondary-structure changes, amyloid-characteristic dye binding,
      and induced birefringence (J. M. Rauceo, N. K. Gaur, K. G. Lee, J. E. Edwards, S.
      A. Klotz, and P. N. Lipke, Infect. Immun. 72:4948-4955, 2004). Therefore, we
      determined whether Als proteins could form amyloid fibers with properties like
      those in cellular aggregation. The beta-aggregation predictor TANGO identified a
      heptapeptide sequence present in a highly conserved sequence with amyloid-forming
      potential in Als1p, Als3p, and Als5p. A tridecapeptide containing this sequence
      formed fibers that bound Congo red and thioflavin T and had characteristic
      amyloid morphology. Als5p(20-431) and Als5p(20-664), large fragments of Als5p
      containing the amyloid sequence, also formed amyloid-like fibers and bound Congo
      red under native conditions. K(a)/K(s) analysis showed that the amyloid-forming
      sequences are highly conserved in Als proteins and evolve more slowly than other
      regions of the proteins. Therefore, amyloid-forming ability itself is conserved
      in these proteins.

PMID- 18083825
TI  - The cytoplasmic region of alpha-1,6-mannosyltransferase Mnn9p is crucial for
      retrograde transport from the Golgi apparatus to the endoplasmic reticulum in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, Och1p and Mnn9p mannosyltransferases are localized
      in the cis-Golgi. Attempts to live image Och1p and Mnn9p tagged with green
      fluorescent protein or red fluorescent protein, respectively, using a high
      performance confocal laser scanning microscope system resulted in simultaneous
      visualization of the native proteins in a living cell. Our observations revealed
      that Och1p and Mnn9p are not always colocalized to the same cisternae. The
      difference in the dynamics of these mannosyltransferases may reflect differences
      in the mechanisms for their retention in the cis-Golgi, since it has been
      reported that Mnn9p cycles between the endoplasmic reticulum and the cis-Golgi
      whereas Och1p does not (Z. Todorow, A. Spang, E. Carmack, J. Yates, and R.
      Schekman, Proc. Natl. Acad. Sci. USA 97:13643-13648, 2000). We investigated the
      localization of chimeric proteins of Mnn9p and Och1p in sec12 and erd1 mutant
      cells. A chimeric protein, M16/O16, which consists of the N-terminal cytoplasmic
      region of Mnn9p and the transmembrane and luminal region of Och1p, behaved like
      Mnn9p, suggesting that the N-terminal cytoplasmic region is important for the
      intracellular dynamics of Mnn9p. This observation is supported by results from
      subcellular-fractionation experiments. Mutational analysis revealed that two
      arginine residues in the N-terminal region of Mnn9p are important for the
      chimeric protein to cycle between the endoplasmic reticulum and the Golgi
      apparatus.

PMID- 18083826
TI  - Effect of hydroxyurea on procyclic Trypanosoma brucei: an unconventional
      mechanism for achieving synchronous growth.
AB  - Procyclic Trypanosoma brucei cells were synchronized with 0.2 mM hydroxyurea. The
      cells did not arrest at the G(1)/S boundary but proceeded through one round of
      replication and arrested near the end of S phase. The mitochondrial genome
      (kinetoplast DNA network) replicated, forming two progeny networks, but the
      repair of minicircle gaps was inhibited.

PMID- 18083827
TI  - Excystation of Eimeria tenella sporozoites impaired by antibody recognizing
      gametocyte/oocyst antigens GAM22 and GAM56.
AB  - Eimeria tenella is the causative agent of coccidiosis in poultry. Infection of
      the chicken intestine begins with ingestion of sporulated oocysts releasing
      sporocysts, which in turn release invasive sporozoites. The monoclonal antibody
      E2E5 recognizes wall-forming body type II (WFBII) in gametocytes and the WFBII
      derived inner wall of oocysts. Here we describe that this antibody also binds to
      the stieda body of sporocysts and significantly impairs in vitro excystation of
      sporozoites. Using affinity chromatography and protein sequence analysis, E2E5 is
      shown to recognize EtGAM56, the E. tenella ortholog of the Eimeria maxima
      gametocyte-specific GAM56 protein. In addition, this antibody was used to screen
      a genomic phage display library presenting E. tenella antigens as fusion proteins
      with the gene VIII product on the surfaces of phagemid particles and identified
      the novel 22-kDa histidine- and proline-rich protein EtGAM22. The Etgam22 mRNA is
      expressed predominantly at the gametocyte stage, as detected by Northern
      blotting. Southern blot analysis in combination with data from the E. tenella
      genome project revealed that Etgam22 is an intronless multicopy gene, with
      approximately 12 to 22 copies in head-to-tail arrangement. Conspicuously, Etgam56
      is also intronless and is localized adjacent to another gam56-like gene, Etgam59.
      Our data suggest that amplification is common for genes encoding oocyst wall
      proteins.

PMID- 18083828
TI  - The L-type calcium ion channel cch1 affects ascospore discharge and mycelial
      growth in the filamentous fungus Gibberella zeae (anamorph Fusarium graminearum).
AB  - Cch1, a putative voltage-gated calcium ion channel, was investigated for its role
      in ascus development in Gibberella zeae. Gene replacement mutants of CCH1 were
      generated and found to have asci which did not forcibly discharge spores,
      although morphologically ascus and ascospore development in the majority of asci
      appeared normal. Additionally, mycelial growth was significantly slower, and
      sexual development was slightly delayed in the mutant; mutant mycelia showed a
      distinctive fluffy morphology, and no cirrhi were produced. Wheat infected with
      Deltacch1 mutants developed symptoms comparable to wheat infected with the wild
      type; however, the mutants showed a reduced ability to protect the infected stalk
      from colonization by saprobic fungi. Transcriptional analysis of gene expression
      in mutants using the Affymetrix Fusarium microarray showed 2,449 genes with
      significant, twofold or greater, changes in transcript abundance across a
      developmental series. This work extends the role of CCH1 to forcible spore
      discharge in G. zeae and suggests that this channel has subtle effects on growth
      and development.

PMID- 18083829
TI  - CTA4 transcription factor mediates induction of nitrosative stress response in
      Candida albicans.
AB  - This work has identified regulatory elements in the major fungal pathogen Candida
      albicans that enable response to nitrosative stress. Nitric oxide (NO) is
      generated by macrophages of the host immune system and commensal bacteria, and
      the ability to resist its toxicity is one adaptation that promotes survival of C.
      albicans inside the human body. Exposing C. albicans to NO induces upregulation
      of the flavohemoglobin Yhb1p. This protein confers protection by enzymatically
      converting NO to harmless nitrate, but it is unknown how C. albicans is able to
      detect NO in its environment and thus initiate this defense only as needed. We
      analyzed this problem by incrementally mutating the YHB1 regulatory region to
      identify a nitric oxide-responsive element (NORE) that is required for NO
      sensitivity. Five transcription factor candidates of the Zn(II)2-Cys6 family were
      then isolated from crude whole-cell extracts by using magnetic beads coated with
      this DNA element. Of the five, only deletion of the CTA4 gene prevented induction
      of YHB1 transcription during nitrosative stress and caused growth sensitivity to
      the NO donor dipropylenetriamine NONOate; Cta4p associates in vivo with NORE DNA
      from the YHB1 regulatory region. Deletion of CTA4 caused a small but significant
      decrease in virulence. A CTA4-dependent putative sulfite transporter encoded by
      SSU1 is also implicated in NO response, but C. albicans ssu1 mutants were not
      sensitive to NO, in contrast to findings in Saccharomyces cerevisiae. Cta4p is
      the first protein found to be necessary for initiating NO response in C.
      albicans.

PMID- 18083830
TI  - Disruption of the PfPK7 gene impairs schizogony and sporogony in the human
      malaria parasite Plasmodium falciparum.
AB  - PfPK7 is an orphan protein kinase of Plasmodium falciparum with maximal homology
      to MEK3/6 and to fungal protein kinase A proteins in its C-terminal and N
      terminal regions, respectively. We showed previously that recombinant PfPK7 is
      active on various substrates but is unable to phosphorylate the Plasmodium
      falciparum mitogen-activated protein kinase homologues, suggesting that it is not
      a MEK functional homologue. Using a reverse genetics approach to investigate the
      function of this enzyme in live parasites, we now show that PfPK7(-) parasite
      clones display phenotypes at two stages of their life cycle: first, a decrease in
      the rate of asexual growth in erythrocytes associated with a lower number of
      daughter merozoites generated per schizont, and second, a dramatic reduction in
      the ability to produce oocysts in the mosquito vector. A normal asexual growth
      rate and the ability to produce oocysts are restored if a functional copy of the
      PfPK7 gene is reintroduced into the PfPK7(-) parasites. Hence, PfPK7 is involved
      in a pathway that regulates parasite proliferation and development.

PMID- 18083831
TI  - Impact of ammonium permeases mepA, mepB, and mepC on nitrogen-regulated secondary
      metabolism in Fusarium fujikuroi.
AB  - In Fusarium fujikuroi, the production of gibberellins and bikaverin is repressed
      by nitrogen sources such as glutamine or ammonium. Sensing and uptake of ammonium
      by specific permeases play key roles in nitrogen metabolism. Here, we describe
      the cloning of three ammonium permease genes, mepA, mepB, and mepC, and their
      participation in ammonium uptake and signal transduction in F. fujikuroi. The
      expression of all three genes is strictly regulated by the nitrogen regulator
      AreA. Severe growth defects of DeltamepB mutants on low-ammonium medium and
      methylamine uptake studies suggest that MepB functions as the main ammonium
      permease in F. fujikuroi. In DeltamepB mutants, nitrogen-regulated genes such as
      the gibberellin and bikaverin biosynthetic genes are derepressed in spite of high
      extracellular ammonium concentrations. mepA mepB and mepC mepB double mutants
      show a similar phenotype as DeltamepB mutants. All three F. fujikuroi mep genes
      fully complemented the Saccharomyces cerevisiae mep1 mep2 mep3 triple mutant to
      restore growth on low-ammonium medium, whereas only MepA and MepC restored
      pseudohyphal growth in the mep2/mep2 mutant. Overexpression of mepC in the
      DeltamepB mutants partially suppressed the growth defect but did not prevent
      derepression of AreA-regulated genes. These studies provide evidence that MepB
      functions as a regulatory element in a nitrogen sensing system in F. fujikuroi
      yet does not provide the sensor activity of Mep2 in yeast, indicating differences
      in the mechanisms by which nitrogen is sensed in S. cerevisiae and F. fujikuroi.

PMID- 18083832
TI  - Atf2 transcription factor binds to the APP1 promoter in Cryptococcus neoformans:
      stimulatory effect of diacylglycerol.
AB  - The fungus Cryptococcus neoformans is an environmental human pathogen which
      enters the lung via the respiratory tract and produces a unique protein, called
      antiphagocytic protein 1 (App1), that protects it from phagocytosis by
      macrophages. In previous studies, we proposed genetic evidences that
      transcription of APP1 is controlled by the enzymatic reaction catalyzed by
      inositol phosphorylceramide synthase 1 (Ipc1) via the production of
      diacylglycerol through the activating transcription factor 2 (Atf2). We
      investigated here the mechanism by which Atf2 binds to the APP1 promoter in vitro
      and in vivo. To this end, we produced Atf2 recombinant proteins (rAtf2) and found
      that rAtf2 binds to ATF cis-acting element present in the APP1 promoter. Indeed,
      mutation of two key nucleotides in the ATF consensus sequence abolishes the
      binding of rAtf2 to the APP1 promoter. Next, we produced C. neoformans strains
      with a hemagglutinin-tagged ATF2 gene and showed that endogenous Atf2 binds to
      APP1 promoter in vivo. Finally, by a novel DNA protein-binding precipitation
      assay, we showed that treatment with 1,2-dioctanoylglycerol positively increases
      binding of Atf2-APP1 promoter in vivo. These studies provide new insights into
      the molecular mechanism by which Atf2 regulates APP1 transcription in vivo with
      important implications for a better understanding of how C. neoformans escapes
      the phagocytic process.

PMID- 18083833
TI  - The E. coli RhlE RNA helicase regulates the function of related RNA helicases
      during ribosome assembly.
AB  - Escherichia coli contains five members of the DEAD-box RNA helicase family, a
      ubiquitous class of proteins characterized by their ability to unwind RNA
      duplexes. Although four of these proteins have been implicated in RNA turnover or
      ribosome biogenesis, no cellular function for the RhlE DEAD-box protein has been
      described as yet. During an analysis of the cold-sensitive growth defect of a
      strain lacking the DeaD/CsdA RNA helicase, rhlE plasmids were identified from a
      chromosomal library as multicopy suppressors of the growth defect. Remarkably,
      when tested for allele specificity, RhlE overproduction was found to exacerbate
      the cold-sensitive growth defect of a strain that lacks the SrmB RNA helicase.
      Moreover, the absence of RhlE exacerbated or alleviated the cold-sensitive defect
      of deaD or srmB strains, respectively. Primer extension and ribosome analysis
      indicated that RhlE regulates the accumulation of immature ribosomal RNA or
      ribosome precursors when deaD or srmB strains are grown at low temperatures. By
      using an epitope-tagged version of RhlE, the majority of RhlE in cell extracts
      was found to cosediment with ribosome-containing fractions. Since both DeaD and
      SrmB have been recently shown to function in ribosome assembly, these findings
      suggests that rhlE genetically interacts with srmB and deaD to modulate their
      function during ribosome maturation. On the basis of the available evidence, I
      propose that RhlE is a novel ribosome assembly factor, which plays a role in the
      interconversion of ribosomal RNA-folding intermediates that are further processed
      by DeaD or SrmB during ribosome maturation.

PMID- 18083834
TI  - Global analysis of mRNA splicing.
AB  - Alternative mRNA splicing is a rich source of transcript diversity in eukaryotic
      cells with broad roles in development and disease. Systems-wide experimental
      methods have started to define how global splicing regulation shapes complex
      biological properties and pathways. Here, we review these approaches, describe
      recent insights they have yielded, and discuss avenues of future investigation.

PMID- 18083835
TI  - Proteasomal degradation of human release factor eRF3a regulates translation
      termination complex formation.
AB  - In eukaryotes, eRF1 and eRF3 are associated in a complex that mediates
      translation termination. The regulation of the formation of this complex in vivo
      is far from being understood. In mammalian cells, depletion of eRF3a causes a
      reduction of eRF1 level by decreasing its stability. Here, we investigate the
      status of eRF3a when not associated with eRF1. We show that eRF3a forms altered
      in their eRF1-binding site have a decreased stability, which increases upon cell
      treatment with the proteasome inhibitor MG132. We also show that eRF3a forms
      altered in eRF1 binding as well as wild-type eRF3a are polyubiquitinated. These
      results indicate that eRF3a is degraded by the proteasome when not associated
      with eRF1 and suggest that proteasomal degradation of eRF3a controls translation
      termination complex formation by adjusting the eRF3a level to that of eRF1.

PMID- 18083836
TI  - Analysis of the human polynucleotide phosphorylase (PNPase) reveals differences
      in RNA binding and response to phosphate compared to its bacterial and
      chloroplast counterparts.
AB  - PNPase is a major exoribonuclease that plays an important role in the
      degradation, processing, and polyadenylation of RNA in prokaryotes and
      organelles. This phosphorolytic processive enzyme uses inorganic phosphate and
      nucleotide diphosphate for degradation and polymerization activities,
      respectively. Its structure and activities are similar to the archaeal exosome
      complex. The human PNPase was recently localized to the intermembrane space (IMS)
      of the mitochondria, and is, therefore, most likely not directly involved in RNA
      metabolism, unlike in bacteria and other organelles. In this work, the
      degradation, polymerization, and RNA-binding properties of the human PNPase were
      analyzed and compared to its bacterial and organellar counterparts.
      Phosphorolytic activity was displayed at lower optimum concentrations of
      inorganic phosphate. Also, the RNA-binding properties to ribohomopolymers varied
      significantly from those of its bacterial and organellar enzymes. The purified
      enzyme did not preferentially bind RNA harboring a poly(A) tail at the 3' end,
      compared to a molecule lacking this tail. Several site-directed mutations at
      conserved amino acid positions either eliminated or modified
      degradation/polymerization activity in different manners than observed for the
      Escherichia coli PNPase and the archaeal and human exosomes. In light of these
      results, a possible function of the human PNPase in the mitochondrial IMS is
      discussed.

PMID- 18083837
TI  - Stable PNPase RNAi silencing: its effect on the processing and adenylation of
      human mitochondrial RNA.
AB  - Polynucleotide phosphorylase (PNPase) is a diverse enzyme, involved in RNA
      polyadenylation, degradation, and processing in prokaryotes and organelles.
      However, in human mitochondria, PNPase is located in the intermembrane space
      (IMS), where no mitochondrial RNA (mtRNA) is known to be present. In order to
      determine the nature and degree of its involvement in mtRNA metabolism, we stably
      silenced PNPase by establishing HeLa cell lines expressing PNPase short-hairpin
      RNA (shRNA). Processing and polyadenylation of mt-mRNAs were significantly
      affected, but, to different degrees in different genes. For instance, the stable
      poly(A) tails at the 3' ends of COX1 transcripts were abolished, while COX3
      poly(A) tails remained unaffected and ND5 and ND3 poly(A) extensions increased in
      length. Despite the lack of polyadenylation at the 3' end, COX1 mRNA and protein
      accumulated to normal levels, as was the case for all 13 mt-encoded proteins.
      Interestingly, ATP depletion also altered poly(A) tail length, demonstrating that
      adenylation of mtRNA can be manipulated by indirect, environmental means and not
      solely by direct enzymatic activity. When both PNPase and the mitochondrial
      poly(A)-polymerase (mtPAP) were concurrently silenced, the mature 3' end of ND3
      mRNA lacked poly(A) tails but retained oligo(A) extensions. Furthermore, in mtPAP
      silenced cells, truncated adenylated COX1 molecules, considered to be degradation
      intermediates, were present but harbored significantly shorter tails. Together,
      these results suggest that an additional mitochondrial polymerase, yet to be
      identified, is responsible for the oligoadenylation of mtRNA and that PNPase,
      although located in the IMS, is involved, most likely by indirect means, in the
      processing and polyadenylation of mtRNA.

PMID- 18083838
TI  - The bacterial toxin RelE induces specific mRNA cleavage in the A site of the
      eukaryote ribosome.
AB  - RelE/RelB is a well-characterized toxin-anti-toxin pair involved in nutritional
      stress responses in Bacteria and Archae. RelE lacks any eukaryote homolog, but we
      demonstrate here that it efficiently and specifically cleaves mRNA in the A site
      of the eukaryote ribosome. The cleavage mechanism is similar to that in bacteria,
      showing the feasibility of A-site cleavage of mRNA for regulatory purposes also
      in eukaryotes. RelE cleavage in the A-site codon of a stalled eukaryote ribosome
      is precise and easily monitored, making "RelE printing" a useful complement to
      toeprinting to determine the exact mRNA location on the eukaryote ribosome and to
      probe the occupancy of its A site.

PMID- 18083839
TI  - GABA(A)-current rundown of temporal lobe epilepsy is associated with repetitive
      activation of GABA(A) "phasic" receptors.
AB  - A study was made of the "rundown" of GABA(A) receptors, microtransplanted to
      Xenopus oocytes from surgically resected brain tissues of patients afflicted with
      drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes,
      isolated from mTLE neocortex specimens, were injected into frog oocytes that
      rapidly incorporated functional GABA(A) receptors. Upon repetitive activation
      with GABA (1 mM), "epileptic" GABA(A) receptors exhibited a GABA(A)-current
      (I(GABA)) rundown that was significantly enhanced by Zn(2+) (</=250 microM), and
      practically abolished by the high-affinity GABA(A) receptor inverse agonist
      SR95531 (gabazine; 2.5-25 microM). Conversely, I(GABA) generated by "control"
      GABA(A) receptors microtransplanted from nonepileptic temporal lobe, lesional
      TLE, or authoptic disease-free tissues remained stable during repetitive
      stimulation, even in oocytes treated with Zn(2+). We conclude that rundown of
      mTLE epileptic receptors depends on the presence of "phasic GABA(A) receptors"
      that have low sensitivity to antagonism by Zn(2+). Additionally, we found that
      GABA(A) receptors, microtransplanted from the cerebral cortex of adult rats
      exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus,
      showed greater rundown than control tissue, an event also occurring in patch
      clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that
      of human mTLE receptors, being enhanced by Zn(2+) (40 microM) and sensitive to
      the antiepileptic agent levetiracetam, the neurotrophin brain-derived
      neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point
      to the rundown of GABA(A) receptors as a hallmark of TLE and suggest that
      modulating tonic and phasic mTLE GABA(A) receptor activity may represent a useful
      therapeutic approach to the disease.

PMID- 18083840
TI  - Autophosphorylation-dependent activation of human Mps1 is required for the
      spindle checkpoint.
AB  - The spindle checkpoint ensures the accuracy of chromosome segregation during
      mitosis. The protein serine/threonine kinase, Mps1, is a critical component of
      the spindle checkpoint in human cells and regulates the kinetochore localization
      of key checkpoint proteins. The kinase activity of Mps1 is required for the
      spindle checkpoint, but how Mps1 is activated during mitosis is unclear. Here, we
      show that the endogenous Mps1 in mitotic HeLa cells is phosphorylated on T676, a
      residue in the activation loop. This phosphorylation event on Mps1 is required
      for its kinase activity in vitro and for spindle checkpoint signaling in vivo.
      T676 phosphorylation of Mps1 increases during mitosis and can occur through
      intermolecular/trans autophosphorylation. Induced dimerization of Mps1 is
      sufficient to activate its kinase activity in cells. We speculate that the
      kinetochore localization of Mps1 raises its local concentration, leading to its
      activation during mitosis through more efficient trans autophosphorylation.

PMID- 18083842
TI  - The product of uncI gene in F1Fo-ATP synthase operon plays a chaperone-like role
      to assist c-ring assembly.
AB  - Bacterial operons for F(1)F(o)-ATP synthase typically include an uncI gene that
      encodes a function-unknown small hydrophobic protein. When we expressed a hybrid
      F(1)F(o) (F(1) from thermophilic Bacillus PS3 and Na(+)-translocating F(o) from
      Propionigenium modestum) in Escherchia coli cells, we found that uncI derived
      from P. modestum was indispensable to produce active enzyme; without uncI, c
      subunits in F(1)F(o) existed as monomers but not as functional c(11)-ring. When
      uncI was expressed from another plasmid at the same time, active F(1)F(o) with
      c(11)-ring was produced. A plasmid containing only uncI and c-subunit gene
      produced c(11)-ring, but a plasmid containing only c-subunit gene did not. Direct
      interaction of UncI protein with c-subunits was suggested from copurification of
      His-tagged UncI protein and c-subunits, both in the state of c(11)-ring and c
      monomers. Na(+) induced dissociation of His-tagged UncI protein from c(11)-ring
      but not from c-monomers. These results show that UncI is a chaperone-like protein
      that assists c(11)-ring assembly from c-monomers in the membrane.

PMID- 18083843
TI  - Spatial heterogeneity of mesopredator release within an oceanic island system.
AB  - Predator-prey communities are ubiquitous in ecology, but introduced predators can
      drive native species to extinction within island systems, prompting the
      eradication of such exotics. Ecological theory predicts that elimination of top
      introduced predators from islands can lead to the counterintuitive decline of
      native prey populations through the ecological release of smaller introduced
      species in a process termed "mesopredator release." We show, in accordance with
      mesopredator release theory and counter to conservation goals for a New Zealand
      island reserve, that initial eradication of cats on Little Barrier Island led to
      reduced breeding success of Cook's petrels, which also are vulnerable to
      predation by a mesopredator, the Pacific rat. The rat's impact on prey
      productivity varied with elevation within the island. Rat eradication was
      followed by a rise in petrel productivity, in support of both ecological theory
      and practical conservation management goals. It appears that interactions among
      introduced predators, native prey, and environmental gradients can drive
      counterintuitive and spatially heterogeneous responses to predator eradications
      from islands. Location-specific, ecosystem-level understanding is essential for
      predicting the outcomes of such restoration management techniques.

PMID- 18083844
TI  - Chemokines and the pathophysiology of neuropathic pain.
AB  - Chemokines and chemokine receptors are widely expressed by cells of the immune
      and nervous systems. This review focuses on our current knowledge concerning the
      role of chemokines in the pathophysiology of chronic pain syndromes. Injury- or
      disease-induced changes in the expression of diverse chemokines and their
      receptors have been demonstrated in the neural and nonneural elements of pain
      pathways. Under these circumstances, chemokines have been shown to modulate the
      electrical activity of neurons by multiple regulatory pathways including
      increases in neurotransmitter release through Ca-dependent mechanisms and
      transactivation of transient receptor channels. Either of these mechanisms alone,
      or in combination, may contribute to sustained excitability of primary afferent
      and secondary neurons within spinal pain pathways. Another manner in which
      chemokines may influence sustained neuronal excitability may be their ability to
      function as excitatory neurotransmitters within the peripheral and central
      nervous system. As is the case for traditional neurotransmitters, injury-induced
      up-regulated chemokines are found within synaptic vesicles. Chemokines released
      after depolarization of the cell membrane can then act on other chemokine
      receptor-bearing neurons, glia, or immune cells. Because up-regulation of
      chemokines and their receptors may be one of the mechanisms that directly or
      indirectly contribute to the development and maintenance of chronic pain, these
      molecules may then represent novel targets for therapeutic intervention in
      chronic pain states.

PMID- 18083845
TI  - Bortezomib induces DNA hypomethylation and silenced gene transcription by
      interfering with Sp1/NF-kappaB-dependent DNA methyltransferase activity in acute
      myeloid leukemia.
AB  - Bortezomib reversibly inhibits 26S proteasomal degradation, interferes with NF
      kappaB, and exhibits antitumor activity in human malignancies. Zinc finger
      protein Sp1 transactivates DNMT1 gene in mice and is functionally regulated
      through protein abundance, posttranslational modifications (ie, ubiquitination),
      or interaction with other transcription factors (ie, NF-kappaB). We hypothesize
      that inhibition of proteasomal degradation and Sp1/NF-kappaB-mediated
      transactivation may impair aberrant DNA methyltransferase activity. We show here
      that, in addition to inducing accumulation of polyubiquitinated proteins and
      abolishment of NF-kappaB activities, bortezomib decreases Sp1 protein levels,
      disrupts the physical interaction of Sp1/NF-kappaB, and prevents binding of the
      Sp1/NF-kappaB complex to the DNMT1 gene promoter. Abrogation of Sp1/NF-kappaB
      complex by bortezomib causes transcriptional repression of DNMT1 gene and down
      regulation of DNMT1 protein, which in turn induces global DNA hypomethylation in
      vitro and in vivo and re-expression of epigenetically silenced genes in human
      cancer cells. The involvement of Sp1/NF-kappaB in DNMT1 regulation is further
      demonstrated by the observation that Sp1 knockdown using mithramycin A or shRNA
      decreases DNMT1 protein levels, which instead are increased by Sp1 or NF-kappaB
      overexpression. Our results unveil the Sp1/NF-kappaB pathway as a modulator of
      DNA methyltransferase activity in human cancer and identify bortezomib as a novel
      epigenetic-targeting drug.

PMID- 18083846
TI  - Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of
      fetal liver with definitive hematopoietic progenitor cells.
AB  - Definitive hematopoietic stem and progenitor cells (HSCs/Ps) originating from the
      yolk sac and/or para-aorta-splanchno-pleura/aorta-gonad-mesonephros are
      hypothesized to colonize the fetal liver, but mechanisms involved are poorly
      defined. The Rac subfamily of Rho GTPases has been shown to play essential roles
      in HSC/P localization to the bone marrow following transplantation. Here, we
      study the role of Rac1 in HSC/P migration during ontogeny and seeding of fetal
      liver. Using a triple-transgenic approach, we have deleted Rac1 in HSCs/Ps during
      very early embryonic development. Without Rac1, there was a decrease in
      circulating HSCs/Ps in the blood of embryonic day (E) 10.5 embryos, while yolk
      sac definitive hematopoiesis was quantitatively normal. Intraembryonic
      hematopoiesis was significantly impaired in Rac1-deficient embryos, culminating
      with absence of intra-aortic clusters and fetal liver hematopoiesis. At E10.5,
      Rac1-deficient HSCs/Ps displayed decreased transwell migration and impaired inter
      action with the microenvironment in migration-dependent assays. These data
      suggest that Rac1 plays an important role in HSC/P migration during embryonic
      development and is essential for the emergence of intraembryonic hematopoiesis.

PMID- 18083847
TI  - Intact apoptosis signaling in myeloid leukemia cells determines treatment outcome
      in childhood AML.
AB  - Recently we reported that intact apoptosis signaling is indicative of favorable
      outcome in childhood acute lymphoblastic leukemia. Here we addressed this issue
      in 45 pediatric acute myeloid leukemia patients analyzing 2 core apoptogenic
      events: cytochrome c release and caspase-3 activation. In patients with good
      prognosis cytochrome c release was clearly found to be caspasedependent and
      correlated with activated caspase-3, indicating that activation of initiator or
      amplifier caspases such as caspase-8 together with an intact apoptosome function
      are elementary for favorable outcome. The functional integrity of this
      apoptogenic checkpoint is reflected by the parameter caspase-dependent cytochrome
      c-related activation of caspase-3 (CRAC(dep)). Patients with positive CRAC(dep)
      values (intact signaling) exhibited superior survival compared with CRAC(dep)
      negative patients (deficient signaling). Thus, the propensity to undergo
      apoptosis of leukemia cells is an important feature for favorable treatment
      outcome and may serve as an additional stratification tool for pediatric AML
      patients. This trial was registered at www.ClinicalTrials.gov as #NCT00111345.

PMID- 18083848
TI  - The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and
      thrombosis.
AB  - Ultralarge von Willebrand factor (UL-VWF) multimers are thought to play a central
      role in pathogenesis of the disease thrombotic thrombocytopenic purpura (TTP);
      however, experimental evidence in support of this hypothesis has been difficult
      to establish. Therefore, to examine directly the requirement for VWF in TTP
      pathogenesis, we generated ADAMTS13-deficient mice on a TTP-susceptible genetic
      background that were also either haploinsufficient (Vwf+/-) or completely
      deficient (Vwf-/-) in VWF. Absence of VWF resulted in complete protection from
      shigatoxin (Stx)-induced thrombocytopenia, demonstrating an absolute requirement
      for VWF in this model (Stx has been shown previously to trigger TTP in ADAMTS13
      deficient mice). We next investigated the requirements for ADAMTS13 and VWF in a
      murine model of endotoxemia. Unlike Stx-induced TTP findings, LPS-induced
      thrombocytopenia and mortality were not affected by either VWF or ADAMTS13
      deficiency, suggesting divergent mechanisms of thrombocytopenia between these 2
      disorders. Finally, we show that VWF deficiency abrogates the ADAMTS13-deficient
      prothrombotic state, suggesting VWF as the only relevant ADAMTS13 substrate under
      these conditions. Together, these findings shed new light on the potential roles
      played by ADAMTS13 and VWF in TTP, endotoxemia, and normal hemostasis.

PMID- 18083849
TI  - Phenotypic and proteomic characterization of multiply antibiotic-resistant
      variants of Salmonella enterica serovar Typhimurium selected following exposure
      to disinfectants.
AB  - In previous work, Salmonella enterica serovar Typhimurium strain SL1344 was
      exposed to sublethal concentrations of three widely used farm disinfectants in
      daily serial passages for 7 days in an attempt to investigate possible links
      between the use of disinfectants and antimicrobial resistance. Stable variants
      OXCR1, QACFGR2, and TOPR2 were obtained following treatment with an oxidizing
      compound blend, a quaternary ammonium disinfectant containing formaldehyde and
      glutaraldehyde, and a tar acid-based disinfectant, respectively. All variants
      exhibited ca. fourfold-reduced susceptibility to ciprofloxacin, chloramphenicol,
      tetracycline, and ampicillin. This coincided with reduced levels of outer
      membrane proteins for all strains and high levels of AcrAB-TolC for OXCR1 and
      QACFGR2, as demonstrated by two-dimensional high-performance liquid
      chromatography-mass spectrometry. The protein profiles of OXCR1 and QACFGR2 were
      similar, but they were different from that of TOPR2. An array of different
      proteins protecting against oxidants, nitroaromatics, disulfides, and peroxides
      were overexpressed in all strains. The growth and motility of variants were
      reduced compared to the growth and motility of the parent strain, the expression
      of several virulence proteins was altered, and the invasiveness in an enteric
      epithelial cell line was reduced. The colony morphology of OXCR1 and QACFGR2 was
      smooth, and both variants exhibited a loss of modal distribution of the
      lipopolysaccharide O-antigen chain length, favoring the production of short O
      antigen chain molecules. Metabolic changes were also detected, suggesting that
      there was increased protein synthesis and a shift from oxidative phosphorylation
      to substrate level phosphorylation. In this study, we obtained evidence that farm
      disinfectants can select for strains with reduced susceptibility to antibiotics,
      and here we describe changes in protein expression in such strains.

PMID- 18083850
TI  - Degradation of glyoxylate and glycolate with ATP synthesis by a thermophilic
      anaerobic bacterium, Moorella sp. strain HUC22-1.
AB  - The thermophilic homoacetogenic bacterium Moorella sp. strain HUC22-1 ferments
      glyoxylate to acetate roughly according to the reaction 2 glyoxylate --> acetate
      + 2 CO(2). A batch culture with glyoxylate and yeast extract yielded 11.7 g per
      mol of cells per substrate, which was much higher than that obtained with H(2)
      plus CO(2). Crude extracts of glyoxylate-grown cells catalyzed the ADP- and NADP
      dependent condensation of glyoxylate and acetyl coenzyme A (acetyl-CoA) to
      pyruvate and CO(2) and converted pyruvate to acetyl-CoA and CO(2), which are the
      key reactions of the malyl-CoA pathway. ATP generation was also detected during
      the key enzyme reactions of this pathway. Furthermore, this bacterium consumed l
      malate, an intermediate in the malyl-CoA pathway, and produced acetate. These
      findings suggest that Moorella sp. strain HUC22-1 can generate ATP by substrate
      level phosphorylation during glyoxylate catabolism through the malyl-CoA pathway.

PMID- 18083851
TI  - Isolation and distribution of a novel iron-oxidizing crenarchaeon from acidic
      geothermal springs in Yellowstone National Park.
AB  - Novel thermophilic crenarchaea have been observed in Fe(III) oxide microbial mats
      of Yellowstone National Park (YNP); however, no definitive work has identified
      specific microorganisms responsible for the oxidation of Fe(II). The objectives
      of the current study were to isolate and characterize an Fe(II)-oxidizing member
      of the Sulfolobales observed in previous 16S rRNA gene surveys and to determine
      the abundance and distribution of close relatives of this organism in acidic
      geothermal springs containing high concentrations of dissolved Fe(II). Here we
      report the isolation and characterization of the novel, Fe(II)-oxidizing,
      thermophilic, acidophilic organism Metallosphaera sp. strain MK1 obtained from a
      well-characterized acid-sulfate-chloride geothermal spring in Norris Geyser
      Basin, YNP. Full-length 16S rRNA gene sequence analysis revealed that strain MK1
      exhibits only 94.9 to 96.1% sequence similarity to other known Metallosphaera
      spp. and less than 89.1% similarity to known Sulfolobus spp. Strain MK1 is a
      facultative chemolithoautotroph with an optimum pH range of 2.0 to 3.0 and an
      optimum temperature range of 65 to 75 degrees C. Strain MK1 grows optimally on
      pyrite or Fe(II) sorbed onto ferrihydrite, exhibiting doubling times between 10
      and 11 h under aerobic conditions (65 degrees C). The distribution and relative
      abundance of MK1-like 16S rRNA gene sequences in 14 acidic geothermal springs
      containing Fe(III) oxide microbial mats were evaluated. Highly related MK1-like
      16S rRNA gene sequences (>99% sequence similarity) were consistently observed in
      Fe(III) oxide mats at temperatures ranging from 55 to 80 degrees C. Quantitative
      PCR using Metallosphaera-specific primers confirmed that organisms highly similar
      to strain MK1 comprised up to 40% of the total archaeal community at selected
      sites. The broad distribution of highly related MK1-like 16S rRNA gene sequences
      in acidic Fe(III) oxide microbial mats is consistent with the observed
      characteristics and growth optima of Metallosphaera-like strain MK1 and
      emphasizes the importance of this newly described taxon in Fe(II)
      chemolithotrophy in acidic high-temperature environments of YNP.

PMID- 18083852
TI  - Quantifying microbial utilization of petroleum hydrocarbons in salt marsh
      sediments by using the 13C content of bacterial rRNA.
AB  - Natural remediation of oil spills is catalyzed by complex microbial consortia.
      Here we took a whole-community approach to investigate bacterial incorporation of
      petroleum hydrocarbons from a simulated oil spill. We utilized the natural
      difference in carbon isotopic abundance between a salt marsh ecosystem supported
      by the 13C-enriched C4 grass Spartina alterniflora and 13C-depleted petroleum to
      monitor changes in the 13C content of biomass. Magnetic bead capture methods for
      selective recovery of bacterial RNA were used to monitor the 13C content of
      bacterial biomass during a 2-week experiment. The data show that by the end of
      the experiment, up to 26% of bacterial biomass was derived from consumption of
      the freshly spilled oil. The results contrast with the inertness of a nearby
      relict spill, which occurred in 1969 in West Falmouth, MA. Sequences of 16S rRNA
      genes from our experimental samples also were consistent with previous reports
      suggesting the importance of Gamma- and Deltaproteobacteria and Firmicutes in the
      remineralization of hydrocarbons. The magnetic bead capture approach makes it
      possible to quantify uptake of petroleum hydrocarbons by microbes in situ.
      Although employed here at the domain level, RNA capture procedures can be highly
      specific. The same strategy could be used with genus-level specificity, something
      which is not currently possible using the 13C content of biomarker lipids.

PMID- 18083853
TI  - Recovery of spores from thermophilic dairy bacilli and effects of their surface
      characteristics on attachment to different surfaces.
AB  - Spores from four Geobacillus spp. were isolated from a milk powder manufacturing
      line in New Zealand. Liquid sporulation media produced spore yields of
      approximately 10(7) spores ml(-1); spores were purified using a two-phase system
      created with polyethylene glycol 4000 and 3 M phosphate buffer. The zeta
      potentials of the spores from the four isolates ranged from -10 to -20 mV at
      neutral pH, with an isoelectric point between pH 3 and 4. Through contact angle
      measurements, spores were found to be hydrophilic and had relative hydrophobicity
      values of 10 to 40%, as measured by the microbial adhesion to hexadecane assay.
      The most hydrophilic spore isolate with the smallest negative charge attached in
      the highest numbers to Thermanox and stainless steel (1 x 10(4) spores cm(-2)),
      with fewer spores attaching to glass (3 x 10(3) spores cm(-2)). However, spores
      produced by the other three strains attached in similar numbers (P > 0.05) to all
      substrata (approximately 1 x 10(3) spores cm(-2)), indicating that there was no
      simple relationship between individual physicochemical interactions and spore
      adherence. Therefore, surface modifications which limit the attachment of one
      strain may not be effective for all stains, and control regimens need to be
      devised with reference to the characteristics of the particular strains of
      concern.

PMID- 18083854
TI  - Detection and identification of fungi intimately associated with the brown
      seaweed Fucus serratus.
AB  - The filamentous fungi associated with healthy and decaying Fucus serratus thalli
      were studied over a 1-year period using isolation methods and molecular
      techniques such as 28S rRNA gene PCR-denaturing gradient gel electrophoresis
      (DGGE) and phylogenetic and real-time PCR analyses. The predominant DGGE bands
      obtained from healthy algal thalli belonged to the Lindra, Lulworthia,
      Engyodontium, Sigmoidea/Corollospora complex, and Emericellopsis/Acremonium-like
      ribotypes. In the culture-based analysis the incidence of recovery was highest
      for Sigmoidea marina isolates. In general, the environmental sequences retrieved
      could be matched unambiguously to isolates recovered from the seaweed except for
      the Emericellopsis/Acremonium-like ribotype, which showed 99% homology with the
      sequences of four different isolates, including that of Acremonium fuci. To
      estimate the extent of colonization of A. fuci, we used a TaqMan real-time
      quantitative PCR assay for intron 3 of the beta-tubulin gene, the probe for which
      proved to be species specific even when it was used in amplifications with high
      background concentrations of other eukaryotic DNAs. The A. fuci sequence was
      detected with both healthy and decaying thalli, but the signal was stronger for
      the latter. Additional sequence types, representing members from the
      Dothideomycetes, were recovered from the decaying thallus DNA, which suggested
      that a change in fungal community structure had occurred. Phylogenetic analysis
      of these environmental sequences and the sequences of isolates and type species
      indicated that the environmental sequences were novel in the Dothideomycetes.

PMID- 18083855
TI  - Anaerobic conditions promote expression of Sfp fimbriae and adherence of sorbitol
      fermenting enterohemorrhagic Escherichia coli O157:NM to human intestinal
      epithelial cells.
AB  - The sfp gene cluster, unique to sorbitol-fermenting (SF) enterohemorrhagic
      Escherichia coli (EHEC) O157:NM strains, encodes fimbriae that mediate mannose
      resistant hemagglutination in laboratory E. coli strains but are not expressed in
      wild-type SF EHEC O157:NM strains under standard laboratory conditions. We
      investigated whether Sfp fimbriae are expressed under conditions that mimic the
      intestinal environment and whether they contribute to the adherence of SF EHEC
      O157:NM strains to human intestinal epithelial cells. The transcription of sfpA
      (encoding the major fimbrial subunit) was upregulated in all strains
      investigated, and all expressed SfpA and possessed fimbriae that reacted with an
      anti-SfpA antibody when the strains were grown on solid media under anaerobic
      conditions. Sfp expression was absent under aerobic conditions and in liquid
      media. Sfp upregulation under anaerobic conditions was significantly higher on
      blood agar and a medium simulating the colonic environment than on a medium
      simulating the ileal environment (P < 0.05). The induction of Sfp fimbriae in SF
      E. coli O157:NM strains correlates with increased adherence to Caco-2 and HCT-8
      cells. Our data indicate that the expression of Sfp fimbriae in SF E. coli
      O157:NM strains is induced under conditions resembling those of the natural site
      of infection and that Sfp fimbriae may contribute to the adherence of the
      organisms to human intestinal epithelium.

PMID- 18083857
TI  - Effect of shadowing on survival of bacteria under conditions simulating the
      Martian atmosphere and UV radiation.
AB  - Spacecraft-associated spores and four non-spore-forming bacterial isolates were
      prepared in Atacama Desert soil suspensions and tested both in solution and in a
      desiccated state to elucidate the shadowing effect of soil particulates on
      bacterial survival under simulated Martian atmospheric and UV irradiation
      conditions. All non-spore-forming cells that were prepared in nutrient-depleted,
      0.2-microm-filtered desert soil (DSE) microcosms and desiccated for 75 days on
      aluminum died, whereas cells prepared similarly in 60-microm-filtered desert soil
      (DS) microcosms survived such conditions. Among the bacterial cells tested,
      Microbacterium schleiferi and Arthrobacter sp. exhibited elevated resistance to
      254-nm UV irradiation (low-pressure Hg lamp), and their survival indices were
      comparable to those of DS- and DSE-associated Bacillus pumilus spores. Desiccated
      DSE-associated spores survived exposure to full Martian UV irradiation (200 to
      400 nm) for 5 min and were only slightly affected by Martian atmospheric
      conditions in the absence of UV irradiation. Although prolonged UV irradiation (5
      min to 12 h) killed substantial portions of the spores in DSE microcosms
      (approximately 5- to 6-log reduction with Martian UV irradiation), dramatic
      survival of spores was apparent in DS-spore microcosms. The survival of soil
      associated wild-type spores under Martian conditions could have repercussions for
      forward contamination of extraterrestrial environments, especially Mars.

PMID- 18083856
TI  - The genome sequence of the metal-mobilizing, extremely thermoacidophilic archaeon
      Metallosphaera sedula provides insights into bioleaching-associated metabolism.
AB  - Despite their taxonomic description, not all members of the order Sulfolobales
      are capable of oxidizing reduced sulfur species, which, in addition to iron
      oxidation, is a desirable trait of biomining microorganisms. However, the
      complete genome sequence of the extremely thermoacidophilic archaeon
      Metallosphaera sedula DSM 5348 (2.2 Mb, approximately 2,300 open reading frames
      [ORFs]) provides insights into biologically catalyzed metal sulfide oxidation.
      Comparative genomics was used to identify pathways and proteins involved
      (directly or indirectly) with bioleaching. As expected, the M. sedula genome
      contains genes related to autotrophic carbon fixation, metal tolerance, and
      adhesion. Also, terminal oxidase cluster organization indicates the presence of
      hybrid quinol-cytochrome oxidase complexes. Comparisons with the mesophilic
      biomining bacterium Acidithiobacillus ferrooxidans ATCC 23270 indicate that the
      M. sedula genome encodes at least one putative rusticyanin, involved in iron
      oxidation, and a putative tetrathionate hydrolase, implicated in sulfur
      oxidation. The fox gene cluster, involved in iron oxidation in the
      thermoacidophilic archaeon Sulfolobus metallicus, was also identified. These iron
      and sulfur-oxidizing components are missing from genomes of nonleaching members
      of the Sulfolobales, such as Sulfolobus solfataricus P2 and Sulfolobus
      acidocaldarius DSM 639. Whole-genome transcriptional response analysis showed
      that 88 ORFs were up-regulated twofold or more in M. sedula upon addition of
      ferrous sulfate to yeast extract-based medium; these included genes for
      components of terminal oxidase clusters predicted to be involved with iron
      oxidation, as well as genes predicted to be involved with sulfur metabolism. Many
      hypothetical proteins were also differentially transcribed, indicating that
      aspects of the iron and sulfur metabolism of M. sedula remain to be identified
      and characterized.

PMID- 18083858
TI  - Heterologous expression of the pneumococcal serotype 14 polysaccharide in
      Lactococcus lactis requires lactococcal epsABC regulatory genes.
AB  - The pneumococcal serotype 14 polysaccharide was produced in Lactococcus lactis by
      coexpressing pneumococcal polysaccharide type 14-specific genes (cpsFGHIJKL(14))
      with the lactococcal regulatory and priming glucosyltransferase-encoding genes
      specific for B40 polysaccharide (epsABCD(B40)). The polysaccharide produced by
      Lactococcus was secreted in the medium, simplifying downstream processing and
      polysaccharide isolation from culture broth.

PMID- 18083859
TI  - Relevant double mutations in bioengineered Streptomyces clavuligerus
      deacetoxycephalosporin C synthase result in higher binding specificities which
      improve penicillin bioconversion.
AB  - Streptomyces clavuligerus deacetoxycephalosporin C synthase (ScDAOCS) is an
      important industrial enzyme for the production of 7-aminodeacetoxycephalosporanic
      acid, which is a precursor for cephalosporin synthesis. Single mutations of six
      amino acid residues, V275, C281, N304, I305, R306, and R307, were previously
      shown to result in enhanced levels of ampicillin conversion, with activities
      ranging from 129 to 346% of the wild-type activity. In this study, these
      mutations were paired to investigate their effects on enzyme catalysis. The
      bioassay results showed that the C-terminal mutations (N304X [where X is alanine,
      leucine, methionine, lysine, or arginine], I305M, R306L, and R307L) in
      combination with C281Y substantially increased the conversion of ampicillin; the
      activity was up to 491% of the wild-type activity. Similar improvements were
      observed for converting carbenicillin (up to 1,347% of the wild-type activity)
      and phenethicillin (up to 1,109% of the wild-type activity). Interestingly, the
      N304X R306L double mutants exhibited lower activities for penicillin G
      conversion, and activities that were 40 to 114% of wild-type enzyme activity were
      detected. Based on kinetic studies using ampicillin, it was clear that the
      increases in the activities of the double mutants relative to those of the
      corresponding single mutants were due to enhanced substrate binding affinities.
      These results also validated the finding that the N304R and I305M mutations are
      ideal for increasing the substrate binding affinity and turnover rate of the
      enzyme, respectively. This study provided further insight into the structure
      function interaction of ScDAOCS with different penicillin substrates, thus
      providing a useful platform for further rational modification of its enzymatic
      properties.

PMID- 18083860
TI  - Development of multiple-locus variable-number tandem-repeat analysis for the
      molecular subtyping of Enterobacter sakazakii.
AB  - The genomic content of Enterobacter sakazakii strain ATCC BAA-894 was analyzed
      for variable-number tandem repeats (VNTRs). In this study we report the
      development of a multiple-locus VNTR analysis (MLVA) strategy for the subtyping
      of E. sakazakii. The method is based on a GeneScan analysis of four VNTR loci
      labeled with multiple fluorescent dyes. This approach was applied to a collection
      of 112 isolates representing all 16 of the currently defined E. sakazakii
      biogroups. MLVA successfully discriminated among these isolates and compared
      favorably with pulsed-field gel electrophoresis. The method was relatively fast
      and easy to perform. The potential value of MLVA as an epidemiological tool is
      discussed.

PMID- 18083861
TI  - "Endomicrobia" and other bacteria associated with the hindgut of Dermolepida
      albohirtum larvae.
AB  - Symbiotic bacteria residing in the hindgut chambers of scarab beetle larvae may
      be useful in paratransgenic approaches to reduce larval root-feeding activities
      on agricultural crops. We compared the bacterial community profiles associated
      with the hindgut walls of individual Dermolepida albohirtum third-instar larvae
      over 2 years and those associated with their plant root food source among
      different geographic regions. Denaturing gradient gel electrophoresis analysis
      was used with universal and Actinobacteria-specific 16S rRNA primers to reveal a
      number of taxa that were found consistently in all D. albohirtum larvae but not
      in samples from their food source, sugarcane roots. These taxa included
      representatives from the "Endomicrobia," Firmicutes, Proteobacteria, and
      Actinobacteria and were related to previously described bacteria from the
      intestines of other scarab larvae and termites. These universally distributed
      taxa have the potential to form vertically transmitted symbiotic associations
      with these insects.

PMID- 18083862
TI  - Suppressing posttranslational gluconoylation of heterologous proteins by
      metabolic engineering of Escherichia coli.
AB  - Minimization of chemical modifications during the production of proteins for
      pharmaceutical and medical applications is of fundamental and practical
      importance. The gluconoylation of heterologously expressed protein which is
      observed in Escherichia coli BL21(DE3) constitutes one such undesired
      posttranslational modification. We postulated that formation of
      gluconoylated/phosphogluconoylated products of heterologous proteins is caused by
      the accumulation of 6-phosphogluconolactone due to the absence of
      phosphogluconolactonase (PGL) in the pentose phosphate pathway. The results
      obtained demonstrate that overexpression of a heterologous PGL in BL21(DE3)
      suppresses the formation of the gluconoylated adducts in the therapeutic proteins
      studied. When this E. coli strain was grown in high-cell-density fed-batch
      cultures with an extra copy of the pgl gene, we found that the biomass yield and
      specific productivity of a heterologous 18-kDa protein increased simultaneously
      by 50 and 60%, respectively. The higher level of PGL expression allowed E. coli
      strain BL21(DE3) to satisfy the extra demand for precursors, as well as the
      energy requirements, in order to replicate plasmid DNA and express heterologous
      genes, as metabolic flux analysis showed by the higher precursor and NADPH fluxes
      through the oxidative branch of the pentose phosphate shunt. This work shows that
      E. coli strain BL21(DE3) can be used as a host to produce three different
      proteins, a heterodimer of liver X receptors, elongin C, and an 18-kDa protein.
      This is the first report describing a novel and general strategy for suppressing
      this nonenzymatic modification by metabolic pathway engineering.

PMID- 18083863
TI  - Effect of pH on intracellular accumulation of trace concentrations of Hg(II) in
      Escherichia coli under anaerobic conditions, as measured using a mer-lux
      bioreporter.
AB  - The effects of pH on the uptake and accumulation of Hg(II) by Escherichia coli
      were determined at trace, environmentally relevant, concentrations of Hg and
      under anaerobic conditions. Hg(II) accumulation was measured using inducible
      light production from E. coli HMS174 harboring a mer-lux bioreporter plasmid
      (pRB28). The effect of pH on the toxicity of higher concentrations of Hg(II) was
      measured using a constitutive lux plasmid (pRB27) in the same bacterial host. In
      this study, intracellular accumulation and toxicity of Hg(II) under anaerobic
      conditions were both significantly enhanced with decreasing pH over the pH range
      of 8 to 5. The pH effect on Hg(II) accumulation was most pronounced at pHs of <6,
      which substantially enhanced the Hg(II)-dependent light response. This enhanced
      response did not appear to be due to pH stress, as similar results were obtained
      whether cells were grown at the same pH as the assay or at a different pH. The
      enhanced accumulation of Hg(II) was also not related to differences in the
      chemical speciation of Hg(II) in the external medium resulting from the changes
      in pH. Experiments with Cd(II), also detectable by the mer-lux bioreporter
      system, showed that Cd(II) accumulation responded differently to pH changes than
      the net accumulation of Hg(II). Potential implications of these findings for our
      understanding of bacterial accumulation of Hg(II) under anaerobic conditions and
      for bacteria-mediated cycling of Hg(II) in aquatic ecosystems are discussed.
      Arguments are provided suggesting that this differential accumulation is due to
      changes in uptake of mercury.

PMID- 18083864
TI  - pH gradient-induced heterogeneity of Fe(III)-reducing microorganisms in coal
      mining-associated lake sediments.
AB  - Lakes formed because of coal mining are characterized by low pH and high
      concentrations of Fe(II) and sulfate. The anoxic sediment is often separated into
      an upper acidic zone (pH 3; zone I) with large amounts of reactive iron and a
      deeper slightly acidic zone (pH 5.5; zone III) with smaller amounts of iron. In
      this study, the impact of pH on the Fe(III)-reducing activities in both of these
      sediment zones was investigated, and molecular analyses that elucidated the
      sediment microbial diversity were performed. Fe(II) was formed in zone I and III
      sediment microcosms at rates that were approximately 710 and 895 nmol cm(-3) day(
      1), respectively. A shift to pH 5.3 conditions increased Fe(II) formation in zone
      I by a factor of 2. A shift to pH 3 conditions inhibited Fe(II) formation in zone
      III. Clone libraries revealed that the majority of the clones from both zones
      (approximately 44%) belonged to the Acidobacteria phylum. Since Acidobacterium
      capsulatum reduced Fe oxides at pHs ranging from 2 to 5, Acidobacteria might be
      involved in the cycling of iron [corrected]. PCR products specific for species
      related to Acidiphilium revealed that there were higher numbers of phylotypes
      related to cultured Acidiphilium or Acidisphaera species in zone III than in zone
      I. From the PCR products obtained for bioleaching-associated bacteria, only one
      phylotype with a level of similarity to Acidithiobacillus ferrooxidans of 99% was
      obtained. Using primer sets specific for Geobacteraceae, PCR products were
      obtained in higher DNA dilutions from zone III than from zone I. Phylogenetic
      analysis of clone libraries obtained from Fe(III)-reducing enrichment cultures
      grown at pH 5.5 revealed that the majority of clones were closely related to
      members of the Betaproteobacteria, primarily species of Thiomonas. Our results
      demonstrated that the upper acidic sediment was inhabited by acidophiles or
      moderate acidophiles which can also reduce Fe(III) under slightly acidic
      conditions. The majority of Fe(III) reducers inhabiting the slightly acidic
      sediment had only minor capacities to be active under acidic conditions.

PMID- 18083865
TI  - Isolation and characterization of Vibrio tubiashii outer membrane proteins and
      determination of a toxR homolog.
AB  - Outer membrane proteins (OMPs) expressed by Vibrio tubiashii under different
      environmental growth conditions were characterized by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, N-terminal amino acid sequencing, and PCR
      analyses. Results showed the presence of a 38- to 40-kDa OmpU-like protein and
      ompU gene, a maltoporin-like protein, several novel OMPs, and a regulatory toxR
      homolog.

PMID- 18083866
TI  - Behavior of Bacillus anthracis strains Sterne and Ames K0610 in sterile raw
      ground beef.
AB  - The behavior of Bacillus anthracis Sterne spores in sterile raw ground beef was
      measured at storage temperatures of 2 to 70 degrees C, encompassing both
      bacterial growth and death. B. anthracis Sterne was weakly inactivated (-0.003 to
      -0.014 log10 CFU/h) at storage temperatures of 2 to 16 degrees C and at
      temperatures greater than and equal to 45 degrees C. Growth was observed from 17
      to 44 degrees C. At these intermediate temperatures, B. anthracis Sterne
      displayed growth patterns with lag, growth, and stationary phases. The lag phase
      duration decreased with increasing temperature and ranged from approximately 3 to
      53 h. The growth rate increased with increasing temperature from 0.011 to 0.496
      log10 CFU/h. Maximum population densities (MPDs) ranged from 5.9 to 7.9 log10
      CFU/g. In addition, the fate of B. anthracis Ames K0610 was measured at 10, 15,
      25, 30, 35, 40, and 70 degrees C to compare its behavior with that of Sterne.
      There were no significant differences between the Ames and Sterne strains for
      both growth rate and lag time. However, the Ames strain displayed an MPD that was
      1.0 to 1.6 times higher than that of the Sterne strain at 30, 35, and 40 degrees
      C. Ames K0610 spores were rapidly inactivated at temperatures greater than or
      equal to 45 degrees C. The inability of B. anthracis to grow between 2 and 16
      degrees C, a relatively low growth rate, and inactivation at elevated
      temperatures would likely reduce the risk for recommended ground-beef handling
      and preparation procedures.

PMID- 18083867
TI  - Novel isolate of Bacillus thuringiensis subsp. thuringiensis that produces a
      quasicuboidal crystal of Cry1Ab21 toxic to larvae of Trichoplusia ni.
AB  - A new isolate (IS5056) of Bacillus thuringiensis subsp. thuringiensis that
      produces a novel variant of Cry1Ab, Cry1Ab21, was isolated from soil collected in
      northeastern Poland. Cry1Ab21 was composed of 1,155 amino acids and had a
      molecular mass of 130.5 kDa, and a single copy of the gene coding for this
      endotoxin was located on a approximately 75-kbp plasmid. When synthesized by the
      wild-type strain, Cry1Ab21 produced a unique, irregular, bipyramidal crystal
      whose long and short axes were both approximately 1 microm long, which gave it a
      cuboidal appearance in wet mount preparations. In diet incorporation bioassays,
      the 50% lethal concentrations of the crystal-spore complex were 16.9 and 29.7
      microg ml(-1) for second- and fourth-instar larvae of the cabbage looper,
      Trichoplusia ni, respectively, but the isolate was essentially nontoxic to larvae
      of the beet armyworm, Spodoptera exigua. A bioassay of autoclaved spore-crystal
      preparations showed no evidence of beta-exotoxin activity, indicating that
      toxicity was due primarily to Cry1Ab21. Studies of the pathogenesis of isolate
      IS5056 in second-instar larvae of T. ni showed that after larval death the
      bacterium colonized and subsequently sporulated extensively throughout the
      cadaver, suggesting that other bacteria inhabiting the midgut lumen played little
      if any role in mortality. As T. ni is among the most destructive pests of
      vegetable crops in North America and has developed resistance to B.
      thuringiensis, this new isolate may have applied value.

PMID- 18083868
TI  - Identification of a ciliate (Oligohymenophorea: Scuticociliatia) associated with
      brown band disease on corals of the Great Barrier Reef.
AB  - A ciliate associated with the coral disease brown band (BrB) was identified as a
      new species belonging to the class Oligohymenophorea, subclass Scuticociliatia.
      The ciliates were characterized by the presence of large numbers of intracellular
      dinoflagellates and displayed an elongated, tube-shaped body structure. They had
      uniform ciliature, except for three distinct cilia in the caudal region, and were
      typically 200 to 400 microm in length and 20 to 50 microm in width.

PMID- 18083869
TI  - Identification by quantitative carrier test of surrogate spore-forming bacteria
      to assess sporicidal chemicals for use against Bacillus anthracis.
AB  - The spores of six strains of Bacillus anthracis (four virulent and two avirulent)
      were compared with those of four other types of spore-forming bacteria for their
      resistance to four liquid chemical sporicides (sodium hypochlorite at 5,000 ppm
      available chlorine, 70,000 ppm accelerated H2O2, 1,000 ppm chlorine dioxide, and
      3,000 ppm peracetic acid). All test bacteria were grown in a 1:10 dilution of
      Columbia broth (with manganese) incubated at 37 degrees C for 72 h. The spore
      suspensions, heat treated at 80 degrees C for 10 min to rid them of any viable
      vegetative cells, contained 1 x 10(8) to 3 x 10(8) CFU/ml. The second tier of the
      quantitative carrier test (QCT-2), a standard of ASTM International, was used to
      assess for sporicidal activity, with disks (1 cm in diameter) of brushed and
      magnetized stainless steel as spore carriers. Each carrier, with 10 microl (> or
      = 10(6) CFU) of the test spore suspension in a soil load, was dried and then
      overlaid with 50 microl of the sporicide being evaluated. The contact time at
      room temperature ranged from 5 to 20 min, and the arbitrarily set criterion for
      acceptable sporicidal activity was a reduction of > or = 10(6) in viable spore
      count. Each test was repeated at least three times. In the final analysis, the
      spores of Bacillus licheniformis (ATCC 14580(T)) and Bacillus subtilis (ATCC
      6051(T)) proved to be generally more resistant than the spores of the strains of
      B. anthracis tested. The use of one or both of the safe and easy-to-handle
      surrogates identified here should help in developing safer and more-effective
      sporicides and also in evaluating the field effectiveness of existing and newer
      formulations in the decontamination of objects and surfaces suspected of B.
      anthracis contamination.

PMID- 18083870
TI  - Root exudates regulate soil fungal community composition and diversity.
AB  - Plants are in constant contact with a community of soil biota that contains fungi
      ranging from pathogenic to symbiotic. A few studies have demonstrated a critical
      role of chemical communication in establishing highly specialized relationships,
      but the general role for root exudates in structuring the soil fungal community
      is poorly described. This study demonstrates that two model plant species
      (Arabidopsis thaliana and Medicago truncatula) are able to maintain resident soil
      fungal populations but unable to maintain nonresident soil fungal populations.
      This is mediated largely through root exudates: the effects of adding in vitro
      generated root exudates to the soil fungal community were qualitatively and
      quantitatively similar to the results observed for plants grown in those same
      soils. This effect is observed for total fungal biomass, phylotype diversity, and
      overall community similarity to the starting community. Nonresident plants and
      root exudates influenced the fungal community by both positively and negatively
      impacting the relative abundance of individual phylotypes. A net increase in
      fungal biomass was observed when nonresident root exudates were added to resident
      plant treatments, suggesting that increases in specific carbon substrates and/or
      signaling compounds support an increased soil fungal population load. This study
      establishes root exudates as a mechanism through which a plant is able to
      regulate soil fungal community composition.

PMID- 18083871
TI  - Depth-resolved quantification of anaerobic toluene degraders and aquifer
      microbial community patterns in distinct redox zones of a tar oil contaminant
      plume.
AB  - Microbial degradation is the only sustainable component of natural attenuation in
      contaminated groundwater environments, yet its controls, especially in anaerobic
      aquifers, are still poorly understood. Hence, putative spatial correlations
      between specific populations of key microbial players and the occurrence of
      respective degradation processes remain to be unraveled. We therefore
      characterized microbial community distribution across a high-resolution depth
      profile of a tar oil-impacted aquifer where benzene, toluene, ethylbenzene, and
      xylene (BTEX) degradation depends mainly on sulfate reduction. We conducted depth
      resolved terminal restriction fragment length polymorphism fingerprinting and
      quantitative PCR of bacterial 16S rRNA and benzylsuccinate synthase genes (bssA)
      to quantify the distribution of total microbiota and specific anaerobic toluene
      degraders. We show that a highly specialized degrader community of microbes
      related to known deltaproteobacterial iron and sulfate reducers (Geobacter and
      Desulfocapsa spp.), as well as clostridial fermenters (Sedimentibacter spp.),
      resides within the biogeochemical gradient zone underneath the highly
      contaminated plume core. This zone, where BTEX compounds and sulfate--an
      important electron acceptor--meet, also harbors a surprisingly high abundance of
      the yet-unidentified anaerobic toluene degraders carrying the previously detected
      F1-cluster bssA genes (C. Winderl, S. Schaefer, and T. Lueders, Environ.
      Microbiol. 9:1035-1046, 2007). Our data suggest that this biogeochemical gradient
      zone is a hot spot of anaerobic toluene degradation. These findings show that the
      distribution of specific aquifer microbiota and degradation processes in
      contaminated aquifers are tightly coupled, which may be of value for the
      assessment and prediction of natural attenuation based on intrinsic aquifer
      microbiota.

PMID- 18083872
TI  - Multiple-locus sequence typing and analysis of toxin genes in Bacillus cereus
      food-borne isolates.
AB  - In the present study we characterized 47 food-borne isolates of Bacillus cereus
      using multilocus sequence typing (MLST). Newly determined sequences were combined
      with sequences available in public data banks in order to produce the largest
      data set possible. Phylogenetic analysis was performed on a total of 296 strains
      for which MLST sequence information is available, and three main lineages--I, II,
      and III--within the B. cereus complex were identified. With few exceptions, all
      food-borne isolates were in group I. The occurrence of horizontal gene transfer
      (HGT) among various strains was analyzed by several statistical methods,
      providing evidence of widespread lateral gene transfer within B. cereus. We also
      investigated the occurrence of toxin-encoding genes, focusing on their
      evolutionary history within B. cereus. Several patterns were identified,
      indicating a pivotal role of HGT in the evolution of toxin-encoding genes. Our
      results indicate that HGT is an important element in shaping the population
      structure of the B. cereus complex. The results presented here also provide
      strong evidence of reticulate evolution within the B. cereus complex.

PMID- 18083873
TI  - Enzymic approach to eurythermalism of Alvinella pompejana and its episymbionts.
AB  - The equilibrium model, which describes the influence of temperature on enzyme
      activity, has been established as a valid and useful tool for characterizing
      enzyme eurythermalism and thermophily. By introducing K(eq), a temperature
      dependent equilibrium constant for the interconversion between E(act), the active
      form of enzyme, and E(inact), a reversibly inactive form of enzyme, the
      equilibrium model currently provides the most complete description of the enzyme
      temperature relationship; its derived parameters are intrinsic and apparently
      universal and, being derived under reaction conditions, potentially have
      physiological significance. One of these parameters, T(eq), correlates with host
      growth temperature better than enzyme stability does. The vent-dwelling annelid
      Alvinella pompejana has been reported as an extremely eurythermal organism, and
      the symbiotic complex microbial community associated with its dorsal surface is
      likely to experience similar environmental thermal conditions. The A. pompejana
      episymbiont community, predominantly composed of epsilonproteobacteria, has been
      analyzed metagenomically, enabling direct retrieval of genes coding for enzymes
      suitable for equilibrium model applications. Two such genes, coding for
      isopropylmalate dehydrogenase and glutamate dehydrogenase, have been isolated
      from the A. pompejana episymbionts, heterologously expressed, and shown by
      reverse transcription-quantitative PCR to be actively expressed. The equilibrium
      model parameters of characterized expression products suggested that enzyme
      eurythermalism constitutes part of the thermal adaptation strategy employed by
      the episymbionts. Moreover, the enzymes' thermal characteristics correspond to
      their predicted physiological roles and the abundance and expression of the
      corresponding genes. This paper demonstrates the use of the equilibrium model as
      part of a top-down metagenomic approach to studying temperature adaptation of
      uncultured organisms.

PMID- 18083874
TI  - Evaluations of different hypervariable regions of archaeal 16S rRNA genes in
      profiling of methanogens by Archaea-specific PCR and denaturing gradient gel
      electrophoresis.
AB  - Different hypervariable (V) regions of the archaeal 16S rRNA gene (rrs) were
      compared systematically to establish a preferred V region(s) for use in Archaea
      specific PCR-denaturing gradient gel electrophoresis (DGGE). The PCR products of
      the V3 region produced the most informative DGGE profiles and permitted
      identification of common methanogens from rumen samples from sheep. This study
      also showed that different methanogens might be detected when different V regions
      are targeted by PCR-DGGE. Dietary fat appeared to transiently stimulate
      Methanosphaera stadtmanae but inhibit Methanobrevibacter sp. strain AbM4 in rumen
      samples.

PMID- 18083876
TI  - Determination of specific growth rate by measurement of specific rate of ribosome
      synthesis in growing and nongrowing cultures of Acinetobacter calcoaceticus.
AB  - RT-RiboSyn measures the specific rate of ribosome synthesis in distinct microbial
      populations by measuring the generation rate of precursor 16S rRNA relative to
      that of mature 16S rRNA when precursor 16S rRNA processing is inhibited. Good
      agreement was demonstrated between specific rate of ribosome synthesis and
      specific growth rate of Acinetobacter calcoaceticus.

PMID- 18083875
TI  - Gnotobiotic mouse immune response induced by Bifidobacterium sp. strains isolated
      from infants.
AB  - Bifidobacterium, which is a dominant genus in infants' fecal flora and can be
      used as a probiotic, has shown beneficial effects in various pathologies,
      including allergic diseases, but its role in immunity has so far been little
      known. Numerous studies have shown the crucial role of the initial intestinal
      colonization in the development of the intestinal immune system, and
      bifidobacteria could play a major role in this process. For a better
      understanding of the effect of Bifidobacterium on the immune system, we aimed at
      determining the impact of Bifidobacterium on the T-helper 1 (T(H)1)/T(H)2 balance
      by using gnotobiotic mice. Germfree mice were inoculated with Bifidobacterium
      longum NCC2705, whose genome is sequenced, and with nine Bifidobacterium strains
      isolated from infants' fecal flora. Five days after inoculation, mice were
      killed. Transforming growth factor beta1 (TGF-beta1), interleukin-4 (IL-4), IL
      10, and gamma interferon (IFN-gamma) gene expressions in the ileum and IFN-gamma,
      tumor necrosis factor alpha (TNF-alpha), IL-10, IL-4, and IL-5 secretions by
      splenocytes cultivated for 48 h with concanavalin A were quantified. Two
      Bifidobacterium species had no effect (B. adolescentis) or little effect (B.
      breve) on the immune system. Bifidobacterium bifidum, Bifidobacterium dentium,
      and one B. longum strain induced T(H)1 and T(H)2 cytokines at the systemic and
      intestinal levels. One B. longum strain induced a T(H)2 orientation with high
      levels of IL-4 and IL-10, both secreted by splenocytes, and of TGF-beta gene
      expression in the ileum. The other two strains induced T(H)1 orientations with
      high levels of IFN-gamma and TNF-alpha splenocyte secretions. Bifidobacterium's
      capacity to stimulate immunity is species specific, but its influence on the
      orientation of the immune system is strain specific.

PMID- 18083878
TI  - Differentiation of Clostridium botulinum serotype A strains by multiple-locus
      variable-number tandem-repeat analysis.
AB  - Ten variable-number tandem-repeat (VNTR) regions identified within the complete
      genomic sequence of Clostridium botulinum strain ATCC 3502 were used to
      characterize 59 C. botulinum strains of the botulism neurotoxin A1 (BoNT/A1) to
      BoNT/A4 (BoNT/A1-A4) subtypes to determine their ability to discriminate among
      the serotype A strains. Two strains representing each of the C. botulinum
      serotypes B to G, including five bivalent strains, and two strains of the closely
      related species Clostridium sporogenes were also tested. Amplified fragment
      length polymorphism analyses revealed the genetic diversity among the serotypes
      and the high degree of similarity among many of the BoNT/A1 strains. The 10 VNTR
      markers amplified fragments within all of the serotype A strains but were less
      successful with strains of other serotypes. The composite multiple-locus VNTR
      analysis of the 59 BoNT/A1-A4 strains and 3 bivalent B strains identified 38
      different genotypes. Thirty genotypes were identified among the 53 BoNT/A1 and
      BoNT/A1(B) strains, demonstrating discrimination below the subtype level.
      Contaminating DNA within crude toxin preparations of three BoNT/A subtypes
      (BoNT/A1 to BoNT/A3) also supported amplification of all of the VNTR regions.
      These markers provide clinical and forensics laboratories with a rapid, highly
      discriminatory tool to distinguish among C. botulinum BoNT/A1 strains for
      investigations of botulism outbreaks.

PMID- 18083879
TI  - Identification of a putative Mexican strain of Serratia entomophila pathogenic
      against root-damaging larvae of Scarabaeidae (Coleoptera).
AB  - The larvae of scarab beetles, known as "white grubs" and belonging to the genera
      Phyllophaga and Anomala (Coleoptera: Scarabaeidae), are regarded as soil-dwelling
      pests in Mexico. During a survey conducted to find pathogenic bacteria with the
      potential to control scarab larvae, a native Serratia sp. (strain Mor4.1) was
      isolated from a dead third-instar Phyllophaga blanchardi larva collected from a
      cornfield in Tres Marias, Morelos, Mexico. Oral bioassays using healthy P.
      blanchardi larvae fed with the Mor4.1 isolate showed that this strain was able to
      cause an antifeeding effect and a significant loss of weight. Mortality was
      observed for P. blanchardi, P. trichodes, and P. obsoleta in a multidose
      experiment. The Mor4.1 isolate also caused 100% mortality 24 h after
      intracoelomic inoculation of the larvae of P. blanchardi, P. ravida, Anomala
      donovani and the lepidopteran insect Manduca sexta. Oral and injection bioassays
      were performed with concentrated culture broths of the Mor4.1 isolate to search
      for disease symptoms and mortality caused by extracellular proteins. The results
      have shown that Mor4.1 broths produce significant antifeeding effects and
      mortality. Mor4.1 broths treated with proteinase K lost the ability to cause
      disease symptoms and mortality, in both the oral and the injection bioassays,
      suggesting the involvement of toxic proteins in the disease. The Mor4.1 isolate
      was identified as a putative Serratia entomophila Mor4.1 strain based on
      numerical taxonomy and phylogenetic analyses done with the 16S rRNA gene
      sequence. The potential of S. entomophila Mor4.1 and its toxins to be used in an
      integrated pest management program is discussed.

PMID- 18083880
TI  - The type II secretion system of Legionella pneumophila elaborates two
      aminopeptidases, as well as a metalloprotease that contributes to differential
      infection among protozoan hosts.
AB  - Legionella pneumophila, the agent of Legionnaires' disease, is an intracellular
      parasite of aquatic amoebae and human macrophages. A key factor for L.
      pneumophila in intracellular infection is its type II protein secretion system
      (Lsp). In order to more completely define Lsp output, we recently performed a
      proteomic analysis of culture supernatants. Based upon the predictions of that
      analysis, we found that L. pneumophila secretes two distinct aminopeptidase
      activities encoded by the genes lapA and lapB. Whereas lapA conferred activity
      against leucine, phenylalanine, and tyrosine aminopeptides, lapB was linked to
      the cleavage of lysine- and arginine-containing substrates. To assess the role of
      secreted aminopeptidases in intracellular infection, we examined the relative
      abilities of lapA and lapB mutants to infect human U937 cell macrophages as well
      as Hartmannella vermiformis and Acanthamoeba castellanii amoebae. Although these
      experiments identified a dispensable role for LapA and LapB, they uncovered a
      previously unrecognized role for the type II-dependent ProA (MspA)
      metalloprotease. Whereas proA mutants were not defective for macrophage or A.
      castellanii infection, they (but not their complemented derivatives) were
      impaired for growth upon coculture with H. vermiformis. Thus, ProA represents the
      first type II effector implicated in an intracellular infection event.
      Furthermore, proA represents an L. pneumophila gene that shows differential
      importance among protozoan infection models, suggesting that the legionellae
      might have evolved some of its factors to especially target certain of their
      protozoan hosts.

PMID- 18083881
TI  - Use of a recombinant fluorescent substrate with cleavage sites for all botulinum
      neurotoxins in high-throughput screening of natural product extracts for
      inhibitors of serotypes A, B, and E.
AB  - The seven serotypes of botulinum neurotoxin (BoNTs) are zinc metalloproteases
      that cleave and inactivate proteins critical for neurotransmission. The
      synaptosomal protein of 25 kDa (SNAP-25) is cleaved by BoNTs A, C, and E, while
      vesicle-associated membrane protein (VAMP) is the substrate for BoNTs B, D, F,
      and G. BoNTs not only are medically useful drugs but also are potential
      bioterrorist and biowarfare threat agents. Because BoNT protease activity is
      required for toxicity, inhibitors of that activity might be effective for
      antibotulinum therapy. To expedite inhibitor discovery, we constructed a hybrid
      gene encoding (from the N terminus to the C terminus, with respect to the
      expressed product) green fluorescent protein, then a SNAP-25 fragment
      encompassing residues Met-127 to Gly-206, and then VAMP residues Met-1 to Lys-94.
      Cysteine was added as the C terminus. The expressed product, which contained the
      protease cleavage sites for all seven botulinum serotypes, was purified and
      coupled covalently through the C-terminal sulfhydryl group to maleimide-activated
      96-well plates. The substrate was readily cleaved by BoNTs A, B, D, E, and F.
      Using this assay and an automated 96-well pipettor, we screened 528 natural
      product extracts for inhibitors of BoNT A, B, and E protease activities. Serotype
      specific inhibition was found in 30 extracts, while 5 others inhibited two
      serotypes.

PMID- 18083877
TI  - Miniprimer PCR, a new lens for viewing the microbial world.
AB  - Molecular methods based on the 16S rRNA gene sequence are used widely in
      microbial ecology to reveal the diversity of microbial populations in
      environmental samples. Here we show that a new PCR method using an engineered
      polymerase and 10-nucleotide "miniprimers" expands the scope of detectable
      sequences beyond those detected by standard methods using longer primers and Taq
      polymerase. After testing the method in silico to identify divergent ribosomal
      genes in previously cloned environmental sequences, we applied the method to soil
      and microbial mat samples, which revealed novel 16S rRNA gene sequences that
      would not have been detected with standard primers. Deeply divergent sequences
      were discovered with high frequency and included representatives that define two
      new division-level taxa, designated CR1 and CR2, suggesting that miniprimer PCR
      may reveal new dimensions of microbial diversity.

PMID- 18083882
TI  - Rottlerin inhibits chlamydial intracellular growth and blocks chlamydial
      acquisition of sphingolipids from host cells.
AB  - We report that rottlerin, a plant-derived compound known to inhibit various
      mammalian kinases, profoundly inhibited chlamydial growth in cell culture with a
      minimal inhibition concentration of 1 microM. The inhibition was effective even
      when rottlerin was added as late as the middle stage of chlamydial infection
      cycle, against multiple Chlamydia species, and in different host cell lines.
      Pretreatment of host cells with rottlerin prior to infection also blocked
      chlamydial growth, suggesting that rottlerin targets host factors. Moreover,
      rottlerin did not alter the chlamydial infection rate and did not directly target
      chlamydial protein synthesis and secretion. The rottlerin-mediated inhibition of
      chlamydial replication and inclusion expansion correlated well with the rottlerin
      induced blockade of host cell sphingolipid trafficking from the Golgi apparatus
      into chlamydial inclusions. These studies not only allowed us to identify a novel
      antimicrobial activity for rottlerin but also allowed us to uncover a potential
      mechanism for rottlerin inhibition of chlamydial growth.

PMID- 18083883
TI  - Characterization of Shiga toxin-producing Escherichia coli isolates associated
      with two multistate food-borne outbreaks that occurred in 2006.
AB  - Shiga toxin-producing Escherichia coli isolates from two 2006 outbreaks were
      compared to other O157:H7 isolates for virulence genotype, biofilm formation, and
      stress responses. Spinach- and lettuce-related-outbreak strains had similar
      pulsed-field gel electrophoresis patterns, and all carried both stx2 and stx2c
      variant genes. Cooperative biofilm formation involving an E. coli O157:H7 strain
      and a non-O157:H7 strain was also demonstrated.

PMID- 18083884
TI  - Comparison of fungal activities on wood and leaf litter in unaltered and nutrient
      enriched headwater streams.
AB  - Fungi are the dominant organisms decomposing leaf litter in streams and mediating
      energy transfer to other trophic levels. However, less is known about their role
      in decomposing submerged wood. This study provides the first estimates of fungal
      production on wood and compares the importance of fungi in the decomposition of
      submerged wood versus that of leaves at the ecosystem scale. We determined fungal
      biomass (ergosterol) and activity associated with randomly collected small wood
      (<40 mm diameter) and leaves in two southern Appalachian streams (reference and
      nutrient enriched) over an annual cycle. Fungal production (from rates of
      radiolabeled acetate incorporation into ergosterol) and microbial respiration on
      wood (per gram of detrital C) were about an order of magnitude lower than those
      on leaves. Microbial activity (per gram of C) was significantly higher in the
      nutrient-enriched stream. Despite a standing crop of wood two to three times
      higher than that of leaves in both streams, fungal production on an areal basis
      was lower on wood than on leaves (4.3 and 15.8 g C m(-2) year(-1) in the
      reference stream; 5.5 and 33.1 g C m(-2) year(-1) in the enriched stream).
      However, since the annual input of wood was five times lower than that of leaves,
      the proportion of organic matter input directly assimilated by fungi was
      comparable for these substrates (15.4 [wood] and 11.3% [leaves] in the reference
      stream; 20.0 [wood] and 20.2% [leaves] in the enriched stream). Despite a
      significantly lower fungal activity on wood than on leaves (per gram of detrital
      C), fungi can be equally important in processing both leaves and wood in streams.

PMID- 18083885
TI  - Rapid DNA library construction for functional genomic and metagenomic screening.
AB  - A rapid protocol was developed for constructing plasmid libraries from small
      quantities of genomic/metagenomic DNA. The technique utilizes linker
      amplification with topoisomerase cloning and allows for inducible transcription
      in Escherichia coli. As proof of principle, several anti-Bacillus lysins were
      cloned from bacteriophage genomes and an aerolysin was cloned from a metagenomic
      sample.

PMID- 18083886
TI  - Sensitivity of an Acinetobacter baylyi mpl mutant to DNA damage.
AB  - A mutant derived from Acinetobacter baylyi ADP1 was isolated from a screen for
      genes involved in the response to DNA damage. This derivative has an insertion in
      the mpl gene which encodes a peptidoglycan-recycling protein. We demonstrate that
      the insertion renders cells sensitive to mitomycin C and to UV.

PMID- 18083887
TI  - The Mucin degrader Akkermansia muciniphila is an abundant resident of the human
      intestinal tract.
AB  - A 16S rRNA-targeted probe, MUC-1437, was designed and validated in order to
      determine the presence and numbers of cells of Akkermansia muciniphila, a mucin
      degrader, in the human intestinal tract. As determined by fluorescent in situ
      hybridization, A. muciniphila accounted more than 1% of the total fecal cells and
      was shown to be a common bacterial component of the human intestinal tract.

PMID- 18083888
TI  - N-glycan modification in Aspergillus species.
AB  - The production by filamentous fungi of therapeutic glycoproteins intended for use
      in mammals is held back by the inherent difference in protein N-glycosylation and
      by the inability of the fungal cell to modify proteins with mammalian
      glycosylation structures. Here, we report protein N-glycan engineering in two
      Aspergillus species. We functionally expressed in the fungal hosts heterologous
      chimeric fusion proteins containing different localization peptides and catalytic
      domains. This strategy allowed the isolation of a strain with a functional alpha
      1,2-mannosidase producing increased amounts of N-glycans of the Man5GlcNAc2 type.
      This strain was further engineered by the introduction of a functional GlcNAc
      transferase I construct yielding GlcNAcMan5GlcNac2 N-glycans. Additionally, we
      deleted algC genes coding for an enzyme involved in an early step of the fungal
      glycosylation pathway yielding Man3GlcNAc2 N-glycans. This modification of fungal
      glycosylation is a step toward the ability to produce humanized complex N-glycans
      on therapeutic proteins in filamentous fungi.

PMID- 18083889
TI  - Nebivolol: pharmacologic profile of an ultraselective, vasodilatory beta1
      blocker.
AB  - Beta-blockers are well-established therapeutic agents in the treatment of
      hypertension and cardiovascular disease. However, these agents are highly
      heterogeneous. Beta-blockers differ in their ancillary pharmacologic properties,
      which are clinically important. Nebivolol is a highly selective beta(1)
      adrenergic receptor blocker that induces vasodilation through stimulation of the
      endothelial nitric oxide/L-arginine pathway. As a racemic mixture of d- and l
      enantiomers, nebivolol is highly lipophilic and rapidly absorbed. Nebivolol
      undergoes extensive hepatic metabolism through the cytochrome P450 2D6 (CYP2D6)
      system. As a result of genetic polymorphisms, CYP2D6 has variable activity,
      manifested by extensive and poor metabolizers of nebivolol. Time to maximum
      concentration is 0.5 to 2 hours, and half-life is 11 hours in extensive
      metabolizers; these values are about 3 times longer in poor metabolizers. Urinary
      and fecal excretion of unchanged nebivolol is less than 0.5% of the dose.
      Nebivolol has a unique hemodynamic profile of reduced systemic vascular
      resistance and increased left ventricular function. These properties are
      attributed to its vasodilating action and contrast with the hemodynamic effects
      of conventional beta-blockers. Nebivolol is thus a novel beta-blocker with
      several important pharmacologic properties that distinguish it from traditional
      beta-blockers. These unique properties may confer clinical benefits beyond simple
      blood pressure lowering.

PMID- 18083890
TI  - Alcohol, wine, and vascular diseases: an abundance of paradoxes.

PMID- 18083891
TI  - Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF
      1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and
      cancer.
AB  - Pulmonary arterial hypertension (PAH) is a lethal syndrome characterized by
      vascular obstruction and right ventricular failure. Although the fundamental
      cause remains elusive, many predisposing and disease-modifying abnormalities
      occur, including endothelial injury/dysfunction, bone morphogenetic protein
      receptor-2 gene mutations, decreased expression of the O(2)-sensitive K(+)
      channel (Kv1.5), transcription factor activation [hypoxia-inducible factor-1alpha
      (HIF-1alpha) and nuclear factor-activating T cells], de novo expression of
      survivin, and increased expression/activity of both serotonin transporters and
      platelet-derived growth factor receptors. Together, these abnormalities create a
      cancerlike, proliferative, apoptosis-resistant phenotype in pulmonary artery
      smooth muscle cells (PASMCs). A possible unifying mechanism for PAH comes from
      studies of fawn-hooded rats, which manifest spontaneous PAH and impaired O(2)
      sensing. PASMC mitochondria normally produce reactive O(2) species (ROS) in
      proportion to P(O2). Superoxide dismutase 2 (SOD2) converts intramitochondrial
      superoxide to diffusible H(2)O(2), which serves as a redox-signaling molecule,
      regulating pulmonary vascular tone and structure through effects on Kv1.5 and
      transcription factors. O(2) sensing is mediated by this mitochondria-ROS-HIF
      1alpha-Kv1.5 pathway. In PAH and cancer, mitochondrial metabolism and redox
      signaling are reversibly disordered, creating a pseudohypoxic redox state
      characterized by normoxic decreases in ROS, a shift from oxidative to glycolytic
      metabolism and HIF-1alpha activation. Three newly recognized mitochondrial
      abnormalities disrupt the mitochondria-ROS-HIF-1alpha-Kv1.5 pathway: 1)
      mitochondrial pyruvate dehydrogenase kinase activation, 2) SOD2 deficiency, and
      3) fragmentation and/or hyperpolarization of the mitochondrial reticulum. The
      pyruvate dehydrogenase kinase inhibitor, dichloroacetate, corrects the
      mitochondrial abnormalities in experimental models of PAH and human cancer,
      causing a regression of both diseases. Mitochondrial abnormalities that disturb
      the ROS-HIF-1alpha-Kv1.5 O(2)-sensing pathway contribute to the pathogenesis of
      PAH and cancer and constitute promising therapeutic targets.

PMID- 18083892
TI  - Integrated multimodal-catheter imaging unveils principal relationships among
      ventricular electrical activity, anatomy, and function.
AB  - Multiple imaging modalities are employed independent of one another while
      managing complex cardiac arrhythmias. To combine electrical, anatomical, and
      functional imaging in a single catheter system, we developed a balloon catheter
      that carried 64 electrodes on its surface and an intracardiac echocardiography
      (ICE) catheter through a central lumen. The catheter system was inserted, and the
      balloon was inflated inside the left ventricle (LV) of eight dogs with 6-wk-old
      infarction, created by occlusion in the left anterior descending coronary artery.
      Anatomy was constructed by ICE imaging (9 MHz) through the balloon. Single-beat
      noncontact mapping (NCM) was performed via the multielectrode array to
      reconstruct unipolar endocardial electrograms during sinus rhythm. Standard
      contact mapping (CM) of the endocardium was also carried out for reference.
      Myocardial infarction in anterior LV extending from the middle to apical regions
      was localized both by ICE and NCM and validated by CM and pathology. The overall
      difference in the activation times between NCM and CM was 3 +/- 1 ms. Unipolar
      voltage in infarcted middle anterior LV was smaller than the voltage in normal
      middle inferior LV both by NCM (11 +/- 4 vs. 16 +/- 3 mV; P = 0.002) and CM (11
      +/- 3 vs. 20 +/- 4 mV; P < 0.001). Unipolar voltage was also inversely related to
      infarct transmurality, both by NCM (r = -0.87; P = 0.005) and CM (r = -0.94; P <
      0.001). The infarct area by ICE (7.7 +/- 2.9 cm(2)) was in agreement with CM
      (bipolar voltage, <1 mV; and area, 7.6 +/- 3.3 cm(2); r = 0.80; P = 0.016).
      Meanwhile, the voltage threshold that depicted the infarct area by NCM was
      directly related to the smallest unipolar voltage reconstructed within the
      infarct (r = 0.96; P < 0.001). In conclusion, combining NCM and ICE imaging in a
      single catheter system is feasible. The preclinical development of such an
      integrated system and its evaluation in experimental myocardial infarction
      demonstrate capabilities for single-beat mapping at multiple sites as well as the
      online assessment of anatomy and myocardial function.

PMID- 18083894
TI  - Exercise induces a cardiac mitochondrial phenotype that resists apoptotic
      stimuli.
AB  - Ischemia-reperfusion-induced calcium overload and production of reactive oxygen
      species can trigger apoptosis by promoting the release of proapoptotic factors
      via the mitochondrial permeability transition pore. While it is clear that
      endurance exercise provides cardioprotection against ischemia-reperfusion-induced
      injury, it is unknown if exercise training directly alters mitochondria phenotype
      and confers protection against apoptotic stimuli in both subsarcolemmal (SS) and
      intermyofibrillar (IMF) mitochondria. We hypothesized that exercise training
      increases expression of endogenous antioxidant enzymes and other antiapoptotic
      proteins, resulting in a SS and IMF mitochondrial phenotype that resists
      apoptotic stimuli. Mitochondria isolated from hearts of sedentary (n = 8) and
      exercised-trained (n = 8) adult male rats were studied. Endurance exercise
      increased the protein levels of primary antioxidant enzymes in both SS and IMF
      mitochondria. Furthermore, exercise increased the levels of antiapoptotic
      proteins in the heart, including the apoptosis repressor with a caspase
      recruitment domain and inducible heat shock protein 70. Importantly, our findings
      reveal that endurance exercise training attenuates reactive oxygen species
      induced cytochrome c release from heart mitochondria. These changes are
      accompanied by a lower maximal rate of mitochondrial permeability transition pore
      opening (V(max)) and prolonged time to V(max) in both SS and IMF cardiac
      mitochondria. These novel findings reveal that endurance exercise promotes
      biochemical alterations in cardiac SS and IMF mitochondria, resulting in a
      phenotype that resists apoptotic stimuli. Furthermore, these results are
      consistent with the concept that exercise-induced mitochondrial adaptations
      contribute to exercise-induced cardioprotection.

PMID- 18083893
TI  - Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats:
      role of PKCdelta.
AB  - We reported previously that simulating sleep apnea by exposing rats to eucapnic
      intermittent hypoxia (E-IH) causes endothelin-dependent hypertension and
      increases constrictor sensitivity to endothelin-1 (ET-1). In addition, augmented
      ET-1-induced constriction in small mesenteric arteries (sMA) is mediated by
      increased Ca(2+) sensitization independent of Rho-associated kinase. We
      hypothesized that exposing rats to E-IH augments ET-1-mediated vasoconstriction
      by increasing protein kinase C (PKC)-dependent Ca(2+) sensitization. In sMA, the
      nonselective PKC inhibitor GF-109203x (3 microM) significantly inhibited ET-1
      stimulated constriction in E-IH arteries but did not affect ET-1-stimulated
      constriction in sham arteries. Phospholipase C inhibitor U-73122 (1 microM) also
      inhibited constriction by ET-1 in E-IH but not sham sMA. In contrast, the
      classical PKC (cPKC) inhibitor Go-6976 (1 microM) had no effect on ET-1-mediated
      vasoconstriction in either group, but a PKCdelta-selective inhibitor (rottlerin,
      3 microM) significantly decreased ET-1-mediated constriction in E-IH but not in
      sham sMA. ET-1 increased PKCdelta phosphorylation in E-IH but not sham sMA. In
      contrast, ET-1 constriction in thoracic aorta from both sham and E-IH rats was
      inhibited by Go-6976 but not by rottlerin. These observations support our
      hypothesis that E-IH exposure significantly increases ET-1-mediated constriction
      of sMA through PKCdelta activation and modestly augments ET-1 contraction in
      thoracic aorta through activation of one or more cPKC isoforms. Therefore,
      upregulation of a PKC pathway may contribute to elevated ET-1-dependent vascular
      resistance in this model of hypertension.

PMID- 18083895
TI  - Cardioprotection with palm oil tocotrienols: comparision of different isomers.
AB  - A recent study from our laboratory indicated the cardioprotective ability of the
      tocotrienol-rich fraction (TRF) from red palm oil. The present study compared
      cardioprotective abilities of different isomers of tocotrienol against TRF as
      recently tocotrienol has been found to function as a potent neuroprotective agent
      against stroke. Rats were randomly assigned to one of the following groups:
      animals were given, by gavage, either 0.35%, 1%, or 3.5% TRF for two different
      periods of time (2 or 4 wk) or 0.03, 0.3, and 3 mg/kg body wt of one of the
      isomers of tocotrienol (alpha, gamma, or delta) for 4 wk; control animals were
      given, by gavage, vehicle only. After 2 or 4 wk, rats were killed, and their
      hearts were then subjected to 30 min of global ischemia followed by 2 h of
      reperfusion. Dose-response and time-response experiments revealed that the
      optimal concentration for TRF was 3.5% TRF and 0.3 mg/kg body wt of tocotrienol
      given for 4 wk. TRF as well as all the isomers of tocotrienol used in our study
      provided cardioprotection, as evidenced by their ability to improve postischemic
      ventricular function and reduce myocardial infarct size. The gamma-isoform of
      tocotrienol was the most cardioprotective of all the isomers followed by the
      alpha- and delta-isoforms. The molecular mechanisms of cardioprotection afforded
      by tocotrienol isoforms were probed by evaluating their respective abilities to
      stabilize the proteasome, allowing it to maintain a balance between prodeath and
      prosurvival signals. Our results demonstrated that tocotrienol isoforms reduced c
      Src but increased the phosphorylation of Akt, thus generating a survival signal.

PMID- 18083896
TI  - Atherosclerotic plaque imaging using phase-contrast X-ray computed tomography.
AB  - Reliable, noninvasive imaging modalities to characterize plaque components are
      clinically desirable for detecting unstable coronary plaques, which cause acute
      coronary syndrome. Although recent clinical developments in computed tomography
      (CT) have enabled the visualization of luminal narrowing and calcified plaques in
      coronary arteries, the identification of noncalcified plaque components remains
      difficult. Phase-contrast X-ray CT imaging has great potentials to reveal the
      structures inside biological soft tissues, because its sensitivity to light
      elements is almost 1,000 times greater than that of absorption-contrast X-ray
      imaging. Moreover, a specific mass density of tissue can be estimated using phase
      contrast X-ray CT. Ex vivo phase-contrast X-ray CT was performed using a
      synchrotron radiation source (SPring-8, Japan) to investigate atherosclerotic
      plaque components of apolipoprotein E-deficient mice. Samples were also
      histologically analyzed. Phase-contrast X-ray CT at a spatial resolution of 10-20
      mum revealed atherosclerotic plaque components easily, and thin fibrous caps were
      detected. The specific mass densities of these plaque components were
      quantitatively estimated. The mass density of lipid area was significantly lower
      (1.011 +/- 0.001766 g/ml) than that of smooth muscle area or collagen area (1.057
      +/- 0.001407 and 1.080 +/- 0.001794 g/ml, respectively). Moreover, the three
      dimensional assessment of plaques could provide their anatomical information.
      Phase-contrast X-ray CT can estimate the tissue mass density of atherosclerotic
      plaques and detect lipid-rich areas. It can be a promising noninvasive technique
      for the investigation of plaque components and detection of unstable coronary
      plaques.

PMID- 18083897
TI  - Treatment with an adenoviral vector encoding hepatocyte growth factor mitigates
      established cardiac dysfunction in doxorubicin-induced cardiomyopathy.
AB  - Hepatocyte growth factor (HGF) reportedly exerts beneficial effects on the heart
      following myocardial infarction and during nonischemic cardiomyopathy, but the
      precise mechanisms underlying the latter have not been well elucidated. We
      generated nonischemic cardiomyopathy in mice by injecting them with doxorubicin
      (15 mg/kg ip). Two weeks later, when cardiac dysfunction was apparent, an
      adenoviral vector encoding human HGF gene (Ad.CAG-HGF, 1x10(11) particles/mouse)
      was injected into the hindlimb muscles; LacZ gene served as the control. Left
      ventricular dilatation and dysfunction normally seen 4 wk after doxorubicin
      administration were significantly mitigated in HGF-treated mice, as were the
      associated cardiomyocyte atrophy/degeneration and myocardial fibrosis. Myocardial
      expression of GATA-4 and a sarcomeric protein, myosin heavy chain, was
      downregulated by doxorubicin, but the expression of both was restored by HGF
      treatment. The protective effect of HGF against doxorubicin-induced cardiomyocyte
      atrophy was confirmed in an in vitro experiment, which also showed that neither
      cardiomyocyte apoptosis nor proliferation plays significant roles in the present
      model. Upregulation of c-Met/HGF receptor was noted in HGF-treated hearts. Among
      the mediators downstream of c-Met, the activation of extracellular signal
      regulated kinase (ERK) was reduced by doxorubicin, but the activity was restored
      by HGF. Levels of transforming growth factor-beta1 and cyclooxygenase-2 did not
      differ between the groups. Our findings suggest the HGF gene delivery exerts
      therapeutic antiatrophic/degenerative and antifibrotic effects on myocardium in
      cases of established cardiac dysfunction caused by doxorubicin. These beneficial
      effects appear to be related to HGF-induced ERK activation and upregulation of c
      Met, GATA-4, and sarcomeric proteins.

PMID- 18083898
TI  - Computational modeling of coupled blood-wall mass transport of LDL: effects of
      local wall shear stress.
AB  - The work herein represents a novel approach for the modeling of low-density
      lipoprotein (LDL) transport from the artery lumen into the arterial wall, taking
      into account the effects of local wall shear stress (WSS) on the endothelial cell
      layer and its pathways of volume and solute flux. We have simulated LDL transport
      in an axisymmetric representation of a stenosed coronary artery, where the
      endothelium is represented by a three-pore model that takes into account the
      contributions of the vesicular pathway, normal junctions, and leaky junctions
      also employing the local WSS to yield the overall volume and solute flux. The
      fraction of leaky junctions is calculated as a function of the local WSS based on
      published experimental data and is used in conjunction with the pore theory to
      determine the transport properties of this pathway. We have found elevated levels
      of solute flux at low shear stress regions because of the presence of a larger
      number of leaky junctions compared with high shear stress regions. Accordingly,
      we were able to observe high LDL concentrations in the arterial wall in these low
      shear stress regions despite increased filtration velocity, indicating that the
      increase in filtration velocity is not sufficient for the convective removal of
      LDL.

PMID- 18083899
TI  - Important role of p38 MAP kinase/NF-kappaB signaling pathway in the sepsis
      induced conversion of cardiac myocytes to a proinflammatory phenotype.
AB  - Septic plasma can convert murine cardiac myocytes to a proinflammatory phenotype.
      These myocytes 1) have increased nuclear levels of nuclear factor-kappaB (NF
      kappaB), 2) release CXC chemokines, and 3) promote polymorphonuclear neutrophil
      (PMN) transendothelial migration. The purpose of the present study was to
      evaluate the role of the mitogen-activated protein (MAP) kinases [p38 MAP kinase,
      extracellular signal-regulated kinase (ERK) 1/2, and c-Jun NH(2)-terminal kinase
      (JNK)] as upstream intracellular signaling components involved in this
      phenomenon. Feces-induced peritonitis (FIP) was employed as a model of sepsis. In
      vitro, cardiac myocytes were treated with plasma (20%) obtained 6 h after either
      sham (saline) or FIP procedures. Myocyte supernatants were used for 1) detection
      of the CXC chemokines (enzyme-linked immunosorbent assay) and 2) assessment of
      their ability to promote PMN transendothelial migration. In vivo, myocardial PMN
      accumulation was assessed by measuring myeloperoxidase (MPO) activity and
      function (dF/dt and heart work). Treatment of cardiac myocytes with septic plasma
      activated p38 MAP kinase and ERK1/2, but not JNK. Blockade approaches (inhibitors
      or small-interference RNA) indicated that only p38 MAP kinase played a role in
      the conversion of the myocytes to a proinflammatory phenotype. Time course
      studies indicated that phosphorylation of p38 MAP kinase preceded the
      phosphorylation of NF-kappaB p65. Inhibition of p38 MAP kinase (SB-202190)
      blocked both NF-kappaB p65 phosphorylation and NF-kappaB nuclear translocation.
      Confirmatory studies in vivo indicated that FIP resulted in an increase in
      myocardial MPO activity and dysfunction, events reversed by the inhibitor of p38
      MAP kinase. Collectively, these data indicate that the cardiomyocyte p38 MAP
      kinase/NF-kappaB signaling pathway plays an important role in the sepsis-induced
      conversion of myocytes to a proinflammatory phenotype.

PMID- 18083901
TI  - Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries.
AB  - The regulation of small artery contractility by vasoconstrictors is important for
      vascular function, and actin cytoskeleton remodeling is required for contraction.
      p38 MAPK and tyrosine kinases are implicated in actin polymerization and
      contraction through heat shock protein 27 (Hsp27) and the cytoskeletal protein
      paxillin, respectively. We evaluated the roles of downstream targets of p38 MAPK
      and tyrosine kinases in cytoskeletal reorganization and contraction and whether
      the two signaling pathways regulate contraction independent of each other. We
      identified the expression of the paxillin homologue hydrogen peroxide-inducible
      clone-5 (Hic-5) and showed its activation by norepinephrine (NE) in a Src
      dependent manner. Furthermore, we demonstrated a NE-induced interaction of
      proline-rich tyrosine kinase-2 (PYK2) but not Src or p125 focal adhesion kinase
      with Hic-5. This interaction was Src dependent, suggesting that Hic-5 was a
      substrate for PYK2 downstream from Src. The activation of Hic-5 induced its
      relocalization to the cytosol. The parallel activation of Hsp27 by NE was p38
      MAPK dependent and led to its dissociation from actin filaments and translocation
      from membrane to cytosol and increased actin polymerization. Both Hsp27 and Hic-5
      activation resulted in their association within the same time frame as NE-induced
      contraction, and the inhibition of either p38 MAPK or Src inhibited the
      interaction between Hsp27 and Hic-5 and the contractile response. Furthermore,
      combined p38 MAPK and Src inhibition had no greater effect on contraction than
      individual inhibition, suggesting that the two pathways act through a common
      mechanism. These data show that NE-induced activation and the association of
      Hsp27 and Hic-5 are required for the reorganization of the actin cytoskeleton and
      force development in small arteries.

PMID- 18083902
TI  - Overexpression of pyruvate dehydrogenase kinase 4 in heart perturbs metabolism
      and exacerbates calcineurin-induced cardiomyopathy.
AB  - The heart adapts to changes in nutritional status and energy demands by adjusting
      its relative metabolism of carbohydrates and fatty acids. Loss of this metabolic
      flexibility such as occurs in diabetes mellitus is associated with cardiovascular
      disease and heart failure. To study the long-term consequences of impaired
      metabolic flexibility, we have generated mice that overexpress pyruvate
      dehydrogenase kinase (PDK)4 selectively in the heart. Hearts from PDK4 transgenic
      mice have a marked decrease in glucose oxidation and a corresponding increase in
      fatty acid catabolism. Although no overt cardiomyopathy was observed in the PDK4
      transgenic mice, introduction of the PDK4 transgene into mice expressing a
      constitutively active form of the phosphatase calcineurin, which causes cardiac
      hypertrophy, caused cardiomyocyte fibrosis and a striking increase in mortality.
      These results demonstrate that cardiac-specific overexpression of PDK4 is
      sufficient to cause a loss of metabolic flexibility that exacerbates
      cardiomyopathy caused by the calcineurin stress-activated pathway.

PMID- 18083903
TI  - Prevention of HIF-1 activation and iNOS gene targeting by low-dose cadmium
      results in loss of myocardial hypoxic preconditioning in the rat.
AB  - This study aimed to underline the interaction between hypoxia-inducible factor-1
      (HIF-1) and the inducible nitric oxide synthase (iNOS) gene in vivo and their
      contribution to the delayed myocardial preconditioning induced by acute
      intermittent hypoxia (IH) in the rat using chromatin immunoprecipitation and
      pharmacological inhibition by low-dose cadmium. Langendorff-perfused hearts of
      Wistar rats exposed to normoxia or IH 24 h earlier were submitted to global
      ischemia and reperfusion. Effects of iNOS inhibition by aminoguanidine (100
      microM) before ischemia or of low-dose injection of cadmium chloride (1 mg/kg)
      before normoxia or IH were tested. Myocardial HIF-1 and iNOS quantification and
      in vivo chromatin immunoprecipitation of HIF-1 bound to the iNOS gene promoter
      were performed. IH-induced delayed cardioprotection resulted in an improvement in
      coronary flow and functional recovery at reperfusion and a decrease in infarct
      size. Myocardial HIF-1 activity was increased with resulting targeting of the
      iNOS gene. Aminoguanidine abolished the cardioprotective effects of IH. Cadmium
      chloride treatment before IH prevented myocardial HIF-1 activation (72.3 +/- 4.0
      vs. 42.1 +/- 9.7 arbitrary units after cadmium chloride; P < 0.05), targeting of
      the iNOS gene, iNOS expression, and preconditioning (infarct size: 15.9 +/- 5.6
      vs. 30.1 +/- 5.4% after cadmium chloride; P < 0.05). This study is the first to
      demonstrate the interaction of HIF-1 with the myocardial iNOS gene in situ after
      hypoxic preconditioning. Prevention of HIF-1 activation and iNOS gene targeting
      by a single low dose of cadmium abolished the delayed cardioprotective effects,
      bringing insight into the cardiovascular consequences of cadmium exposure.

PMID- 18083904
TI  - Metabolic response to an acute jump in cardiac workload: effects on malonyl-CoA,
      mechanical efficiency, and fatty acid oxidation.
AB  - Inhibition of myocardial fatty acid oxidation can improve left ventricular (LV)
      mechanical efficiency by increasing LV power for a given rate of myocardial
      energy expenditure. This phenomenon has not been assessed at high workloads in
      nonischemic myocardium; therefore, we subjected in vivo pig hearts to a high
      workload for 5 min and assessed whether blocking mitochondrial fatty acid
      oxidation with the carnitine palmitoyltransferase-I inhibitor oxfenicine would
      improve LV mechanical efficiency. In addition, the cardiac content of malonyl-CoA
      (an endogenous inhibitor of carnitine palmitoyltransferase-I) and activity of
      acetyl-CoA carboxylase (which synthesizes malonyl-CoA) were assessed. Increased
      workload was induced by aortic constriction and dobutamine infusion, and LV
      efficiency was calculated from the LV pressure-volume loop and LV energy
      expenditure. In untreated pigs, the increase in LV power resulted in a 2.5-fold
      increase in fatty acid oxidation and cardiac malonyl-CoA content but did not
      affect the activation state of acetyl-CoA carboxylase. The activation state of
      the acetyl-CoA carboxylase inhibitory kinase AMP-activated protein kinase
      decreased by 40% with increased cardiac workload. Pretreatment with oxfenicine
      inhibited fatty acid oxidation by 75% and had no effect on cardiac energy
      expenditure but significantly increased LV power and LV efficiency (37 +/- 5% vs.
      26 +/- 5%, P < 0.05) at high workload. In conclusion, 1) myocardial fatty acid
      oxidation increases with a short-term increase in cardiac workload, despite an
      increase in malonyl-CoA concentration, and 2) inhibition of fatty acid oxidation
      improves LV mechanical efficiency by increasing LV power without affecting
      cardiac energy expenditure.

PMID- 18083900
TI  - Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension:
      studies in dopamine receptor knockout mice.
AB  - Dopamine plays an important role in the pathogenesis of hypertension by
      regulating epithelial sodium transport and by interacting with vasoactive
      hormones/humoral factors, such as aldosterone, angiotensin, catecholamines,
      endothelin, oxytocin, prolactin pro-opiomelancortin, reactive oxygen species,
      renin, and vasopressin. Dopamine receptors are classified into D(1)-like (D(1)
      and D(5)) and D(2)-like (D(2), D(3), and D(4)) subtypes based on their structure
      and pharmacology. In recent years, mice deficient in one or more of the five
      dopamine receptor subtypes have been generated, leading to a better understanding
      of the physiological role of each of the dopamine receptor subtypes. This review
      summarizes the results from studies of various dopamine receptor mutant mice on
      the role of individual dopamine receptor subtypes and their interactions with
      other G protein-coupled receptors in the regulation of blood pressure.

PMID- 18083906
TI  - Kinesin steps do not alternate in size.
AB  - Kinesin is a two-headed motor protein that transports cargo inside cells by
      moving stepwise on microtubules. Its exact trajectory along the microtubule is
      unknown: alternative pathway models predict either uniform 8-nm steps or
      alternating 7- and 9-nm steps. By analyzing single-molecule stepping traces from
      "limping" kinesin molecules, we were able to distinguish alternate fast- and slow
      phase steps and thereby to calculate the step sizes associated with the motions
      of each of the two heads. We also compiled step distances from nonlimping kinesin
      molecules and compared these distributions against models predicting uniform or
      alternating step sizes. In both cases, we find that kinesin takes uniform 8-nm
      steps, a result that strongly constrains the allowed models.

PMID- 18083905
TI  - Particulate matter air pollution exposure promotes recruitment of monocytes into
      atherosclerotic plaques.
AB  - Epidemiologic studies have shown an association between exposure to ambient
      particulate air pollution <10 microm in diameter (PM(10)) and increased
      cardiovascular morbidity and mortality. We previously showed that PM(10) exposure
      causes progression of atherosclerosis in coronary arteries. We postulate that the
      recruitment of monocytes from the circulation into atherosclerotic lesions is a
      key step in this PM(10)-induced acceleration of atherosclerosis. The study
      objective was to quantify the recruitment of circulating monocytes into vessel
      walls and the progression of atherosclerotic plaques induced by exposure to
      PM(10). Female Watanabe heritable hyperlipidemic rabbits, which naturally develop
      systemic atherosclerosis, were exposed to PM(10) (EHC-93) or vehicle by
      intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-bromo
      2'-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole
      blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in
      recipients was measured by quantitative histological methodology. Exposure to
      PM(10) caused progression of atherosclerotic lesions in thoracic and abdominal
      aorta. It also decreased circulating monocyte counts, decreased circulating
      monocytes expressing high levels of CD31 (platelet endothelial cell adhesion
      molecule-1) and CD49d (very late antigen-4 alpha-chain), and increased expression
      of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM(10) increased the
      number of BrdU-labeled monocytes adherent to endothelium over plaques and
      increased the migration of BrdU-labeled monocytes into plaques and smooth muscle
      underneath plaques. We conclude that exposure to ambient air pollution particles
      promotes the recruitment of circulating monocytes into atherosclerotic plaques
      and speculate that this is a critically important step in the PM(10)-induced
      progression of atherosclerosis.

PMID- 18083907
TI  - Minichromosome analysis of chromosome pairing, disjunction, and sister chromatid
      cohesion in maize.
AB  - With the advent of engineered minichromosome technology in plants, an
      understanding of the properties of small chromosomes is desirable. Twenty-two
      minichromosomes of related origin but varying in size are described that provide
      a unique resource to study such behavior. Fourteen minichromosomes from this set
      could pair with each other in meiotic prophase at frequencies between 25 and
      100%, but for the smaller chromosomes, the sister chromatids precociously
      separated in anaphase I. The other eight minichromosomes did not pair with
      themselves, and the sister chromatids divided equationally at meiosis I. In
      plants containing one minichromosome, the sister chromatids also separated at
      meiosis I. In anaphase II, the minichromosomes progressed to one pole or the
      other. The maize (Zea mays) Shugoshin protein, which has been hypothesized to
      protect centromere cohesion in meiosis I, is still present at anaphase I on
      minichromosomes that divide equationally. Also, there were no differences in the
      level of phosphorylation of Ser-10 of histone H3, a correlate of cohesion, in the
      minichromosomes in which sister chromatids separated during anaphase I compared
      with the normal chromosomes. These analyses suggest that meiotic centromeric
      cohesion is compromised in minichromosomes depending on their size and cannot be
      maintained by the mechanisms used by normal-sized chromosomes.

PMID- 18083908
TI  - Exploring the molecular etiology of dominant-negative mutations.

PMID- 18083909
TI  - Gibberellin regulates pollen viability and pollen tube growth in rice.
AB  - Gibberellins (GAs) play many biological roles in higher plants. We collected and
      performed genetic analysis on rice (Oryza sativa) GA-related mutants, including
      GA-deficient and GA-insensitive mutants. Genetic analysis of the mutants revealed
      that rice GA-deficient mutations are not transmitted as Mendelian traits to the
      next generation following self-pollination of F1 heterozygous plants, although GA
      insensitive mutations are transmitted normally. To understand these differences
      in transmission, we examined the effect of GA on microsporogenesis and pollen
      tube elongation in rice using new GA-deficient and GA-insensitive mutants that
      produce semifertile flowers. Phenotypic analysis revealed that the GA-deficient
      mutant reduced pollen elongation1 is defective in pollen tube elongation,
      resulting in a low fertilization frequency, whereas the GA-insensitive
      semidominant mutant Slr1-d3 is mainly defective in viable pollen production.
      Quantitative RT-PCR revealed that GA biosynthesis genes tested whose mutations
      are transmitted to the next generation at a lower frequency are preferentially
      expressed after meiosis during pollen development, but expression is absent or
      very low before the meiosis stage, whereas GA signal-related genes are actively
      expressed before meiosis. Based on these observations, we predict that the
      transmission of GA-signaling genes occurs in a sporophytic manner, since the
      protein products and/or mRNA transcripts of these genes may be introduced into
      pollen-carrying mutant alleles, whereas GA synthesis genes are transmitted in a
      gametophytic manner, since these genes are preferentially expressed after
      meiosis.

PMID- 18083910
TI  - Natural variation in RPS2-mediated resistance among Arabidopsis accessions:
      correlation between gene expression profiles and phenotypic responses.
AB  - Natural variation in gene expression (expression traits or e-traits) is
      increasingly used for the discovery of genes controlling traits. An important
      question is whether a particular e-trait is correlated with a phenotypic trait.
      Here, we examined the correlations between phenotypic traits and e-traits among
      10 Arabidopsis thaliana accessions. We studied defense against Pseudomonas
      syringae pv tomato DC3000 (Pst), with a focus on resistance gene-mediated
      resistance triggered by the type III effector protein AvrRpt2. As phenotypic
      traits, we measured growth of the bacteria and extent of the hypersensitive
      response (HR) as measured by electrolyte leakage. Genetic variation among
      accessions affected growth of Pst both with (Pst avrRpt2) and without (Pst) the
      AvrRpt2 effector. Variation in HR was not correlated with variation in bacterial
      growth. We also collected gene expression profiles 6 h after mock and Pst avrRpt2
      inoculation using a custom microarray. Clusters of genes whose expression levels
      are correlated with bacterial growth or electrolyte leakage were identified.
      Thus, we demonstrated that variation in gene expression profiles of Arabidopsis
      accessions collected at one time point under one experimental condition has the
      power to explain variation in phenotypic responses to pathogen attack.

PMID- 18083911
TI  - Trace amine-associated receptor 1 modulates dopaminergic activity.
AB  - The recent identification of the trace amine-associated receptor (TAAR)1 provides
      an opportunity to dissociate the effects of trace amines on the dopamine
      transporter from receptor-mediated effects. To separate both effects on a
      physiological level, a Taar1 knockout mouse line was generated. Taar1 knockout
      mice display increased sensitivity to amphetamine as revealed by enhanced
      amphetamine-triggered increases in locomotor activity and augmented striatal
      release of dopamine compared with wild-type animals. Under baseline conditions,
      locomotion and extracellular striatal dopamine levels were similar between Taar1
      knockout and wild-type mice. Electrophysiological recordings revealed an elevated
      spontaneous firing rate of dopaminergic neurons in the ventral tegmental area of
      Taar1 knock-out mice. The endogenous TAAR1 agonist p-tyramine specifically
      decreased the spike frequency of these neurons in wild-type but not in Taar1
      knockout mice, consistent with the prominent expression of Taar1 in the ventral
      tegmental area. Taken together, the data reveal TAAR1 as regulator of
      dopaminergic neurotransmission.

PMID- 18083912
TI  - Inhibition of geranylgeranyl diphosphate synthase induces apoptosis through
      multiple mechanisms and displays synergy with inhibition of other isoprenoid
      biosynthetic enzymes.
AB  - Inhibitors of isoprenoid synthesis are widely used for treatment of human
      diseases, including hypercholesterolemia and osteoporosis, and they have the
      potential to be useful for treatment of cancer. Statin drugs inhibit the enzyme
      HMG-CoA reductase, whereas nitrogenous bisphosphonates have more recently been
      shown to inhibit farnesyl disphosphate synthase. In addition, our laboratory has
      recently developed several potent and specific bisphosphonate inhibitors of
      geranylgeranyl diphosphate synthase, including digeranyl bisphosphonate. Because
      all three enzymes fall in the same biosynthetic pathway and many of the
      biological effects are due to depletion of downstream products, we hypothesized
      that simultaneous inhibition of these enzymes would result in synergistic growth
      inhibition. In this study, we show that inhibition of geranylgeranyl diphosphate
      synthase induces apoptosis in K562 leukemia cells. This induction of apoptosis is
      in part dependent upon both geranylgeranyl diphosphate depletion and accumulation
      of farnesyl diphosphate. Combinations of either lovastatin or zoledronate with
      digeranyl bisphosphonate synergistically inhibited growth and induced apoptosis.
      These combinations also potently inhibited cellular geranylgeranylation. These
      results support the potential for combinations of multiple inhibitors of isoprene
      biosynthesis to inhibit cancer cell growth or metastasis at clinically achievable
      concentrations.

PMID- 18083916
TI  - Surviving cancer or other serious illness: a review of individual and community
      resources.
AB  - In order to provide appropriate individual and community support for cancer
      survivors, there is a great need to better understand how people who have
      survived cancer or other serious illness adapt positively to health challenges
      and to identify effective approaches for helping people cope with health
      challenges over their lifetime. Studies have identified a number of personal
      factors that are associated with resilience, increased quality of life, and
      positive adaptation to illness. Of particular interest is the ability of
      individuals to survive or even thrive despite an adverse event, as influenced by
      both individual factors such as resiliency and external factors like social
      support. The experience of having a potentially life-threatening illness can lead
      to positive adaptation and increased ability to thrive despite difficult
      circumstances. The cancer survivorship movement and the cancer community in
      general provide important resources for improving quality of life and alleviating
      human suffering and distress among patients and survivors and for adding personal
      meaning and hope to people's lives.

PMID- 18083913
TI  - Studies with an orally bioavailable alpha V integrin antagonist in animal models
      of ocular vasculopathy: retinal neovascularization in mice and retinal vascular
      permeability in diabetic rats.
AB  - The alpha(V) integrins are key receptors involved in mediating cell migration and
      angiogenesis. In age-related macular degeneration (AMD) and diabetic retinopathy,
      angiogenesis plays a critical role in the loss of vision. These ocular
      vasculopathies might be treatable with a suitable alpha(V) antagonist, and an
      oral drug would offer a distinct advantage over current therapies. (3,S,beta,S)
      1,2,3,4-Tetrahydro-beta-[[1-[1-oxo-3-(1,5,6,7-tetrahydro-1,8-naphthyridin-2
      yl)propyl]-4-piperidinyl]methyl]-3-quinolinepropanoic acid (JNJ-26076713) is a
      potent, orally bioavailable, nonpeptide alpha(V) antagonist derived from the
      arginine-glycine-asparagine binding motif in the matrix protein ligands (e.g.,
      vitronectin). This compound inhibits alpha(V)beta(3) and alpha(V)beta(5) binding
      to vitronectin in the low nanomolar range, it has excellent selectivity over
      integrins alpha(IIb)beta(3) and alpha(5)beta(1), and it prevents adhesion to
      human, rat, and mouse endothelial cells. JNJ-26076713 blocks cell migration
      induced by vascular endothelial growth factor, fibroblast growth factor (FGF),
      and serum, and angiogenesis induced by FGF in the chick chorioallantoic membrane
      model. JNJ-26076713 is the first alpha(V) antagonist reported to inhibit retinal
      neovascularization in an oxygen-induced model of retinopathy of prematurity after
      oral administration. In diabetic rats, orally administered JNJ-26076713 markedly
      inhibits retinal vascular permeability, a key early event in diabetic macular
      edema and AMD. Given this profile, JNJ-26076713 represents a potential
      therapeutic candidate for the treatment of age-related macular degeneration,
      macular edema, and proliferative diabetic retinopathy.

PMID- 18083917
TI  - The second conference on skeletal medicine and biology: overview and some
      comments.

PMID- 18083918
TI  - Intracellular protein degradation from a vague idea through the lysosome and the
      ubiquitin-proteasome system and on to human diseases and drug targeting: Nobel
      Lecture, December 8, 2004.
AB  - Between the 1950s and 1980s, scientists were focusing mostly on how the genetic
      code is transcribed to RNA and translated to proteins, but how proteins are
      degraded has remained a neglected research area. With the discovery of the
      lysosome by Christian de Duve, it was assumed that cellular proteins are degraded
      within this organelle. Yet, several independent lines of experimental evidence
      strongly suggested that intracellular proteolysis is largely nonlysosomal, but
      the mechanisms involved had remained obscure. The discovery of the ubiquitin
      proteasome system resolved this enigma. We now recognize that ubiquitin- and
      proteasome-mediated degradation of intracellular proteins is involved in the
      regulation of a broad array of cellular processes, such as cell cycle and
      division, regulation of transcription factors, and assurance of the cellular
      quality control. Not surprisingly, aberrations in the system have been implicated
      in the pathogenesis of many human diseases, malignancies, and neurodegenerative
      disorders among them, which led subsequently to an increasing effort to develop
      mechanism-based drugs; one is already in use.

PMID- 18083919
TI  - Multiplicity of BMP signaling in skeletal development.
AB  - Skeletal development and homeostasis are complex processes involving systemic
      regulatory factors and local factors present in the bone microenvironment. Among
      these factors, bone morphogenetic proteins (BMPs) represent the major potent bone
      morphogens, which coordinate with other factors to exert their multiple functions
      by regulating cell condensation, as well as inducing chondrogenesis and
      osteogenesis. This article reviews the current status of BMP signaling in
      skeletal development, with focus on regulation at the level of the receptors.
      Crosstalk of the BMP pathway with other major signaling pathways is also
      summarized.

PMID- 18083920
TI  - Nephroblastoma overexpressed (Nov) is a novel bone morphogenetic protein
      antagonist.
AB  - Nephroblastoma overexpressed (Nov), a member of the CCN family of proteins, is
      expressed by osteoblasts and its transcription is regulated by transforming
      growth factor (TGF)-beta and bone morphogenetic proteins (BMP). CCN proteins can
      interact with TGF-beta, BMPs, and Wnt. We explored the function of Nov in
      skeletal cells, in vitro and in vivo. Constitutive overexpression of Nov in cells
      of the osteoblastic lineage impaired osteoblastic differentiation, opposed the
      biological effects of BMP-2 and Wnt 3 and impaired BMP-2 and Wnt signaling,
      indicating that Nov has BMP-2 antagonistic activity. Transgenic mice
      overexpressing Nov under the control of the osteocalcin promoter exhibited
      osteopenia secondary to decreased bone formation, confirming the effects in
      vitro. GST pulldown experiments demonstrated direct Nov-BMP interactions. In
      conclusion, Nov has BMP antagonistic properties and inhibits osteoblastogenesis
      and osteoblastic function.

PMID- 18083921
TI  - The role of the perichondrium in fetal bone development.
AB  - Most cells in mesenchymal condensations that form endochondral bone become
      chondrocytes; cells at the outer edges of the condensations, however, become
      perichondrial cells with distinct properties and functions. Some perichondrial
      cells become osteoblasts that populate both the future cortical and trabecular
      bone; others probably become chondrocytes. Perichondrial cells both send signals
      to the underlying growth cartilage and receive signals from the cartilage. Here I
      illustrate briefly examples of the complicated interactions between the
      perichondrium and the underlying growth cartilage.

PMID- 18083922
TI  - The PTHrP functional domain is at the gates of endochondral bones.
AB  - PTHrP gene-expression products are generally of very low abundance. The PTHrP
      lacZ knockin mouse is a useful tool in this regard, identifying PTHrP expression
      in previously unrecognized sites and serving to score this expression in gene
      regulation experiments. These sites include the periosteum and ligament/tendon
      insertion sites at the surface of endochondral bones, in which PTHrP appears to
      regulate subjacent bone cell populations. As mesenchymal condensations chondrify,
      PTHrP/lacZ is also expressed in epiphyseal cartilage (the chondroepiphysis), and
      this structure contributes PTHrP-expressing chondrocyte populations to both
      articular cartilage and growth-plate cartilage when these structures take shape
      postnatally. The Indian hedgehog-PTHrP axis is fully deployed in both of these
      locations and in articular cartilage appears to protect the joint space from
      invasion by mineralizing cells. In most of these sites PTHrP is mechanically
      regulated.

PMID- 18083923
TI  - Axin1 and Axin2 are regulated by TGF- and mediate cross-talk between TGF- and Wnt
      signaling pathways.
AB  - Chondrocyte maturation during endochondral bone formation is regulated by a
      number of signals that either promote or inhibit maturation. Among these, two
      well-studied signaling pathways play crucial roles in modulating chondrocyte
      maturation: transforming growth factor-beta (TGF-beta)/Smad3 signaling slows the
      rate of chondrocyte maturation, while Wingless/INT-1-related (Wnt)/beta-catenin
      signaling enhances the rate of chondrocyte maturation. Axin1 and Axin2 are
      functionally equivalent and have been shown to inhibit Wnt/beta-catenin signaling
      and stimulate TGF-beta signaling. Here we show that while Wnt3a stimulates Axin2
      in a negative feedback loop, TGF-beta suppresses the expression of both Axin1 and
      Axin2 and stimulates beta-catenin signaling. In Axin2 -/- chondrocytes, TGF-beta
      treatment results in a sustained increase in beta-catenin levels compared to wild
      type chondrocytes. In contrast, overexpression of Axin enhanced TGF-beta
      signaling while overexpression of beta-catenin inhibited the ability of TGF-beta
      to induce Smad3-sensitive reporters. Finally, the suppression of the Axins is
      Smad3-dependent since the effect is absent in Smad3 -/- chondrocytes. Altogether
      these findings show that the Axins act to integrate signals between the Wnt/beta
      catenin and TGF-beta/Smad pathways. Since the suppression Axin1 and Axin2
      expression by TGF-beta reduces TGF-beta signaling and enhances Wnt/beta-catenin
      signaling, the overall effect is a shift from TGF-beta toward Wnt/beta-catenin
      signaling and an acceleration of chondrocyte maturation.

PMID- 18083924
TI  - Synovial joint formation during mouse limb skeletogenesis: roles of Indian
      hedgehog signaling.
AB  - Indian hedgehog (Ihh) has been previously found to regulate synovial joint
      formation. To analyze mechanisms, we carried out morphological, molecular, and
      cell fate map analyses of interzone and joint development in wild-type and Ihh(-/
      ) mouse embryo long bones. We found that Ihh(-/-) cartilaginous digit anlagen
      remained fused and lacked interzones or mature joints, whereas wrist skeletal
      elements were not fused but their joints were morphologically abnormal. E14.5 and
      E17.5 wild-type digit and ankle prospective joints expressed hedgehog target
      genes including Gli1 and Gli2 and interzone-associated genes including Gdf5, Erg,
      and tenascin-C, but expression of all these genes was barely detectable in mutant
      joints. For cell fate map analysis of joint progenitor cells, we mated Gdf5
      Cre(+/-)/Rosa R26R(+/-) double transgenic mice with heterozygous Ihh(+/-) mice
      and monitored reporter beta-galactosidase activity and gene expression in triple
      transgenic progeny. In control Gdf5-Cre(+/-)/R26R(+/-)/Ihh(+/-) limbs, reporter
      positive cells were present in developing interzones, articulating layers, and
      synovial lining tissue and absent from underlying growth plates. In mutant Gdf5
      Cre(+/-)/R26R(+/-)/Ihh(-/-) specimens, reporter-positive cells were present also.
      However, the cells were mostly located around the prospective and uninterrupted
      digit joint sites and, interestingly, still expressed Erg, tenascin-C, and Gdf5.
      Topographical analysis revealed that interzone and associated cells were not
      uniformly distributed, but were much more numerous ventrally. A similar
      topographical bias was seen for cavitation process and capsule primordia
      formation. In sum, Ihh is a critical and possibly direct regulator of joint
      development. In its absence, distribution and function of Gdf5-expressing
      interzone-associated cells are abnormal, but their patterning at prospective
      joint sites still occurs. The joint-forming functions of the cells appear to
      normally involve a previously unsuspected asymmetric distribution along the
      ventral-to-dorsal plane of the developing joint.

PMID- 18083925
TI  - Differential effects of vascular endothelial growth factor on joint formation
      during limb development.
AB  - During skeletal development the proliferating chondrocytes choose between two
      fates: to differentiate into prejoint cells or undergo hypertrophy. Vascular
      endothelial growth factor (VEGF) participates in endochondral ossification, but
      it is unknown whether it has a role in joint development. We evaluated the VEGF
      effects on joints, implanting VEGF-beads in the presumptive limb joints of chick
      embryos. The wrist and elbow showed partial and complete fusions. Using the model
      of ectopic digits induced by transforming growth factor-beta (TGF-beta), VEGF
      inhibited joint formation when it was applied after TGF-beta. These data suggest
      differential effects of VEGF on different joints during development.

PMID- 18083926
TI  - A novel transgenic mouse model to study the osteoblast lineage in vivo.
AB  - Over the past few decades, osteoblast differentiation has been studied
      extensively in a variety of culture systems and findings from these experiments
      have shaped our understanding of the bone-forming cell lineage. However, in vitro
      assays are bound by intrinsic limitations and are unable to effectively mirror
      many aspects related to osteoblasts in vivo, including their origin, destiny, and
      life span. Therefore, these fundamental questions strongly advocate the need for
      novel models to characterize the osteoblast lineage in vivo. Here, we developed a
      transgenic mouse system to study stage-specific subsets of osteoblast lineage
      cells. We believe that this system will prove to be a helpful tool in deciphering
      multiple aspects of osteoblast biology in vivo.

PMID- 18083927
TI  - Control of postnatal bone mass by the zinc finger adapter protein Schnurri-3.
AB  - The completed skeleton undergoes continuous remodeling for the duration of adult
      life. Rates of bone formation by osteoblasts and bone resorption by osteoclasts
      determine adult bone mass. Abnormalities in either the osteoblast or osteoclast
      compartment affect bone mass and result in skeletal disorders, the most common of
      which is osteoporosis, a state of low bone mass. Much is known about the
      molecular control of bone formation and resorption from rare single gene
      disorders resulting in elevated or reduced bone mass. Such genetic disorders can
      be attributed either to osteoclast deficiencies, collectively termed
      "osteopetrosis," or to intrinsically elevated osteoblast activity, termed
      "osteosclerosis." However, an increasing need for anabolic therapies to prevent
      age-induced bone loss has stimulated a search for additional genes that act at
      the level of the osteoblast to regulate matrix synthesis. Recently, we have
      discovered a zinc finger adaptor protein called Schnurri-3 (Shn3) that potently
      regulates adult bone mass. Mice that lack Shn3 have normal skeletal morphogenesis
      but display profoundly elevated bone mass that increases with age. The molecular
      mechanism was revealed to be the recruitment of WWP1, a Nedd4 family E3 ubiquitin
      ligase, by Shn3 to the major transcriptional regulator of the osteoblast, Runx2.
      In the absence of Shn3, Runx2 degradation by WWP1 is inhibited resulting in
      increased levels of Runx2 protein and enhanced expression of Runx2 target genes
      leading to increased osteoblast synthetic activity. Small molecules that inhibit
      Shn3 or WWP1 may be attractive candidates for the treatment of diseases of low
      bone mass.

PMID- 18083928
TI  - Transcriptional regulation of osteoblasts.
AB  - The differentiation of osteoblasts from mesenchymal precursors requires a series
      of cell fate decisions controlled by a hierarchy of transcription factors. Among
      these are RUNX2, Osterix (OSX), ATF4, and a large number of nuclear coregulators.
      During bone development, initial RUNX2 expression coincides with the formation of
      mesenchymal condensations well before the branching of chondrogenic and
      osteogenic lineages. Given that RUNX2 is expressed so early and participates in
      several stages of bone formation, it is not surprising that it is subject to a
      variety of controls. These include regulation by nuclear accessory factors and
      posttranslational modification, especially phosphorylation. Specific examples of
      RUNX2 regulation include interactions with DLX proteins and ATF4 and
      phosphorylation by the ERK/MAP kinase pathway. RUNX2 is regulated via
      phosphorylation of critical serine residues in the P/S/T domain. MAPK activation
      of RUNX2 was also found to occur in vivo. Transgenic expression of constitutively
      active MEK1 in osteoblasts accelerated skeletal development while a dominant
      negative MEK1 retarded development in a RUNX2-dependent manner. These studies
      allow us to begin understanding the complex mechanisms necessary to fine-tune
      bone formation in response to extracellular stimuli including ECM interactions,
      mechanical loads, and hormonal stimulation.

PMID- 18083929
TI  - Identification of additional dimerization partners of FIAT, the factor inhibiting
      ATF4-mediated transcription.
AB  - FIAT is a leucine zipper protein whose name was coined for its interaction with
      ATF4 and the subsequent blockage of ATF4-directed osteocalcin gene transcription.
      FIAT is a nuclear protein that lacks a basic DNA-binding domain but contains
      three identifiable leucine zipper domains. FIAT heterodimerizes with ATF4 through
      one of these zippers and thereby prohibits ATF4 from binding to its cognate DNA
      sequence. We tested whether FIAT also interacts with additional basic domain
      leucine zipper transcriptional regulators of osteoblast activity, such as the Fos
      family member Fra-1 or one of its dimerization partners, c-Jun. Transient
      transfection assays in osteoblastic MC3T3-E1 cells with the heterologous AP-1-tk
      luciferase reporter revealed that FIAT does not affect c-Jun-mediated
      transcription, even in the presence of the c-Jun coactivator alphaNAC. However,
      FIAT inhibited transcriptional activation by a c-Jun~Fra-1 heterodimer. Thus FIAT
      specifically inhibits Fra-1 transcriptional activity. These data identify a
      second target of the FIAT transcriptional repressor activity and suggest that
      FIAT can modulate early osteoblast activity by interacting with ATF4, as well as
      regulate later osteoblast function through inhibition of Fra-1.

PMID- 18083930
TI  - The role of NFAT in osteoclast formation.
AB  - Osteoclasts are cells of monocyte-macrophage origin that degrade bone matrix.
      Receptor activator of NF-kappaB ligand (RANKL) induces osteoclast formation in
      the presence of macrophage-colony-stimulating factor (M-CSF) and costimulatory
      signals. RANKL induces activation of the TNF receptor-associated factor 6 (TRAF6)
      and c-Fos pathways, which lead to the osteoclast-specific event, that is,
      autoamplification of nuclear factor of activated T cells (NFAT)c1, the master
      transcription factor for osteoclast differentiation. Autoamplification of NFATc1
      is dependent on the calcium signaling of immunoglobulin-like receptors associated
      with immunoreceptor tyrosine-based activation motif (ITAM)-harboring adaptors. In
      addition to the calcineurin-NFATc1 axis, calcium signaling activates the
      calmodulin-dependent kinase pathway, which also plays a critical role in
      osteoclast formation. Such advances in the understanding of the molecular
      mechanism of osteoclast differentiation are expected to lead to novel therapeutic
      approaches to bone diseases.

PMID- 18083931
TI  - Mechanisms of osteoclastic secretion.
AB  - A tight balance between bone resorption by osteoclasts and bone formation by
      osteoblasts is required for the maintenance of bone mass and integrity. A net
      increase in bone resorption over formation results in osteoporosis, a disease
      associated with significantly morbidity and mortality. Following attachment via
      the integrin alphavbeta3, osteoclasts degrade bone by generation of the ruffled
      border, the unique resorptive organelle of the cell. The adherent cell then
      secretes into the subcellular space protons and acidic proteases. We review here
      the concepts relating to the mechanisms of regulated secretion and provide
      preliminary data on the role of one protein important for secretion by
      osteoclasts.

PMID- 18083932
TI  - New roles for osteoclasts in bone.
AB  - Osteoclasts have long been recognized as the cells that resorb bone in normal
      bone remodeling and in pathologic conditions in which bone resorption is
      increased. They are derived from precursors in the mononuclear phagocyte lineage,
      which arise in the bone marrow and fuse with one another to form the
      multinucleated cells that resorb calcified matrixes under the influence of
      osteoblastic cells in bone marrow. There is growing evidence that osteoclast
      precursors (OCPs) and osteoclasts have functions in and around bone other than
      bone resorption. For example, they modulate the differentiation of other cells,
      including osteoblastic cells; they regulate hematopoietic stem cell movement from
      the bone marrow to the bloodstream; and they are secretory cells that participate
      in immune responses. In this article, we review these findings, which support new
      roles for osteoclasts and OCPs in the growing field of osteoimmunology and in
      common pathologic conditions affecting bones and joints.

PMID- 18083933
TI  - Similarities and contrasts in ryanodine receptor localization and function in
      osteoclasts and striated muscle cells.
AB  - This review compares ryanodine receptor (RyR)-mediated Ca(2+) signaling processes
      in muscle and osteoclast cells. In muscle, RyR-mediated release of an
      intracellularly stored, sarcoplasmic reticular (SR), Ca(2+) is triggered by
      voltage-sensitive dihydropyridine receptor (DHPR)-L-type Ca(2+) channels either
      through an allosteric coupling with the RyR in skeletal muscle or a Ca(2+)
      induced Ca(2+) release initiated by extracellular Ca(2+) entry in cardiac muscle.
      Both cell subtypes are nevertheless capable of Ca(2+)-induced SR Ca(2+) release
      with cardiac muscle additionally showing a store overload-induced Ca(2+) release
      (SOICR) driven by SR luminal Ca(2+) under some pathological conditions.
      Osteoclasts similarly show cytosolic Ca(2+) elevations driven by release of
      intracellular Ca(2+) stores that culminate in motile activity in turn modifying
      bone resorptive activity. However, such triggering is controlled by ambient
      Ca(2+) rather than membrane potential with features strongly suggestive of
      control by a surface membrane Ca(2+) receptor. Yet common actions of the RyR
      specific agents perchlorate, dantrolene Na, ryanodine, caffeine, adenosine 3',5'
      cyclic diphosphate ribose (cADPr) and ruthenium red implicate RyR in signaling in
      all these cell types. These findings were reconciled by reports confirming and
      uniquely localizing a cell surface rather than microsomal osteoclastic RyR that
      might itself detect ambient Ca(2+) possibly through its otherwise intraluminal
      positioned low-affinity Ca(2+)-binding site in parallel with the SOICR mechanism
      in cardiac muscle. Such a mechanism could interact with other osteoclast
      processes transferring Ca(2+) between cytosol, intracellular stores and
      extracellular space and be integrated with systemic processes regulating Ca(2+)
      homeostasis.

PMID- 18083934
TI  - Proteomic analysis of hydroxyapatite interaction proteins in bone.
AB  - Biomineralization involves proteins and/or other macromolecules directly in
      controlling the mineral crystal nucleation/induction, growth, and maturation. To
      identify these proteins in bone, bovine bone EDTA/NaCl extract was passed through
      a hydroxyapatite column followed by washing with 0.5 M NaCl and the bound
      proteins were collected and analyzed by mass spectrometry. More than 30 proteins
      were identified. While as described previously, albumin, alpha2-HS glycoprotein,
      decorin, biglycan, osteoadherin, osteonectin, etc. were included, collagen alpha2
      (I), matrix extracellular phosphoglycoprotein, secreted phosphoprotein 24,
      chondroadherin, lumican, perlecan, thrombospondin 1, nucleobindin, etc. were for
      the first time shown to directly interact with calcium phosphate mineral.

PMID- 18083935
TI  - Glucocorticoids and the osteoclast.
AB  - Glucocorticoid (GC)-induced bone loss is the most common cause of secondary
      osteoporosis but its pathogenesis is controversial. GCs clearly suppress bone
      formation in vivo but the means by which they impact osteoblasts is unclear.
      Because bone remodeling is characterized by tethering of the activities of the
      two cells, the osteoclast is a potential modulator of the effect of GCs on
      osteoblasts. To address this issue we compared the effects of dexamethasone on
      wild-type (WT) osteoclasts with those derived from mice with disruption of the GC
      receptor in osteoclast lineage cells and found that the bone-degrading capacity
      of GC-treated WT cells is suppressed. The inhibitory effect of dexamethasone on
      bone resorption reflects failure of osteoclasts to organize their cytoskeleton in
      response to M-CSF. Dexamethasone specifically arrests M-CSF activation of RhoA,
      Rac, and Vav3, each of which regulate the osteoclast cytoskeleton. In all
      circumstances, mice lacking the GC receptor in osteoclast lineage cells are
      spared the impact of dexamethasone on osteoclasts and their precursors.
      Consistent with osteoclasts modulating the osteoblast-suppressive effect of
      dexamethasone, GC receptor-deficient mice are protected from the steroid's
      inhibition of bone formation.

PMID- 18083936
TI  - Vitamin D: molecular mechanism of action.
AB  - Vitamin D maintains calcium homeostasis and is required for bone development and
      maintenance. Recent evidence has indicated an interrelationship between vitamin D
      and health beyond bone, including effects on cell proliferation and on the immune
      system. New developments in our lab related to the function and regulation of
      target proteins have provided novel insights into the mechanisms of vitamin D
      action. Studies in our lab have shown that the calcium-binding protein,
      calbindin, which has been reported to be a facilitator of calcium diffusion, also
      has an important role in protecting against apoptotic cell death in different
      tissues including protection against cytokine destruction of osteoblastic and
      pancreatic beta cells. These findings have important implications for the
      therapeutic intervention of many disorders including diabetes and osteoporosis.
      Recent studies in our laboratory of intestinal calcium absorption using calbindin
      D(9k) null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D(3)
      (1,25(OH)(2)D(3)) inducible epithelial calcium channel, TRPV6, provide evidence
      for the first time of calbindin-D(9k) and TRPV6 independent regulation of active
      calcium absorption. Besides calbindin, the other major target of 1,25(OH)(2)D(3)
      in intestine and kidney is 25(OH)D(3) 24 hydroxylase (24(OH)ase), which is
      involved in the catabolism of 1,25(OH)(2)D(3). In our laboratory we have
      identified various factors that cooperate with the vitamin D receptor in
      regulating 24(OH)ase expression including C/EBP beta, SWI/SNF (complexes that
      remodel chromatin using the energy of ATP hydrolysis) and the methyltransferases,
      CARM1 and G9a. Evidence is also presented for C/EBP beta as a nuclear coupling
      factor that coordinates regulation of osteopontin by 1,25(OH)(2)D(3) and PTH. Our
      findings define novel mechanisms that may be of fundamental importance in
      understanding how 1,25(OH)(2)D(3) mediates its multiple biological effects.

PMID- 18083937
TI  - Parathyroid hormone stimulation of noncanonical Wnt signaling in bone.
AB  - In bone, parathyroid hormone (PTH) exerts either a catabolic or an anabolic
      effect depending on its method of administration. This paradoxical action has led
      to the use of PTH as an effective treatment for osteoporosis. The Wnt family of
      signaling proteins has a critical role in multiple events, which are necessary
      for proper animal development and survival, yet their exact method of action in
      bone remains elusive. We have uncovered a novel link between Wnt-4 and PTH. We
      think that, in bone, Wnt-4 signaling in response to PTH implicates cross-talk of
      multiple signaling pathways. This work hopes to further elucidate Wnt signaling
      in bone and provide greater understanding of PTH's anabolic effects in bone.

PMID- 18083938
TI  - T cells: unexpected players in the bone loss induced by estrogen deficiency and
      in basal bone homeostasis.
AB  - The bone-immune interface has become a subject of intense interest in recent
      years. It has long been recognized that infection, inflammation, and autoimmune
      disorders are associated with systemic and local bone loss. Yet, it is only
      recently that T lymphocytes and their products have been recognized as key
      regulators of osteoclast formation, life span, and activity. Similarly, sex
      steroids and aging have been known to regulate the immune system and T cells for
      decades. In spite of the abundance of clinical and physiological clues, it is
      only in the last few years that investigators have linked immune cells to the
      etiology of postmenopausal and senile osteoporosis, as well as to the bone loss
      caused by a variety of endocrine conditions. As surprising is new evidence
      showing that in contrast to their bone destructive effects under certain
      pathological conditions, T cells are highly protective of basal bone homeostasis,
      through complex regulatory effects on osteoprotegerin (OPG) production by B
      cells, involving CD40 to CD40 Ligand (CD40L) costimulation. This article examines
      the experimental evidence suggesting that estrogen prevents bone loss by
      regulating T cell function, and that T cell costimulation with B cells is
      critical for OPG production and maintenance of basal bone homeostasis.

PMID- 18083939
TI  - Proresorptive actions of FSH and bone loss.
AB  - We review studies that propose follicle-stimulating hormone (FSH) as a
      physiologic stimulator of osteoclastic bone resorption. We hypothesize that, in
      addition to low estrogen, a rising FSH contributes to the increased bone
      resorption and bone loss in hypergonadism. This is of particular relevance to the
      perimenopausal transition, wherein profound bone loss is accompanied by
      trabecular perforations in the face of high FSH and normal estrogen levels.
      Potential therapeutic implications include the development of antagonists to both
      circulating FSH and its osteoclastic receptor.

PMID- 18083940
TI  - Bone loss in thyroid disease: role of low TSH and high thyroid hormone.
AB  - More than 10% of postmenopausal women in the United States receive thyroid
      hormone replacement therapy and up to 20% of these women are over-replaced
      inducing subclinical hyperthyroidism. Because hyperthyroidism and post menopausal
      osteoporosis overlap in women of advancing age, it is urgent to understand the
      effect of thyroid hormone excess on bone. We can now provide results that not
      thyroid hormones but also TSH itself has an equally important role to play in
      bone remodeling.

PMID- 18083941
TI  - Hematopoietic stem cell trafficking: regulated adhesion and attraction to bone
      marrow microenvironment.
AB  - Hematopoiesis takes place preferentially within bone cavities, suggesting that
      bone-derived factors contribute to blood formation. Hematopoietic stem and
      progenitor cells (HSPCs) can be mobilized from the bone marrow parenchyma to the
      circulation by various agonists whose common downstream action leads to
      alteration in the expression or function of the chemokine CXCL12 and adhesion
      molecules mediating migration. Granulocyte colony-stimulating factor (G-CSF), the
      most prevalent drug used to mobilize HSPCs, dramatically suppresses osteoblast
      function. Recent studies suggest that G-CSF-mediated suppression requires signals
      from the sympathetic nervous system (SNS). This review summarizes emerging
      concepts thought to contribute to stem cell migration.

PMID- 18083942
TI  - Evolution, aging, and osteoporosis.
AB  - Aging is a process whereby organisms lose to the capacity to effectively handle
      life's stresses. Associated with aging are pathophysiological processes, such as
      decreases in bone mass, which in the extreme form lead to significant morbidity.
      Evolutionary theory suggests that these pathophysiological processes are
      permitted to occur because an organism need only preserve its body against stress
      only for the amount of time needed for effective reproduction. In this review, an
      understanding of osteoporosis and bone loss is discussed within the context of
      aging theory. Specific topics covered include: (1) bone loss as an
      antagonistically pleiotropic physiological process, (2) age-associated stress
      accumulation and its negative impact on bone turnover, and (3) the mechanisms
      whereby gonadal failure, increases in inflammatory cytokines, and cellular bone
      marrow changes lead to bone loss. This review concludes by examining purported
      hypotheses in the context of Werner's syndrome, a disease characterized by
      premature aging. We suggest that future osteoporosis therapy will likely focus on
      prevention of aging in general as a means to prevent the development of
      osteoporosis.

PMID- 18083943
TI  - Cardiovascular risk prediction: are we there yet?

PMID- 18083944
TI  - Resynchronisation therapy in heart failure: searching for predictors.

PMID- 18083945
TI  - BNP: not just for heart failure.

PMID- 18083947
TI  - Pacing in heart failure: how many leads and where?

PMID- 18083946
TI  - Maximising secondary prevention therapies in patients with coronary heart
      disease.

PMID- 18083948
TI  - Value of ST-resolution analysis in the era of primary percutaneous coronary
      intervention.

PMID- 18083949
TI  - Epidemiology and causation of coronary heart disease and stroke in India.
AB  - Cardiovascular diseases are major causes of mortality and disease in the Indian
      subcontinent, causing more than 25% of deaths. It has been predicted that these
      diseases will increase rapidly in India and this country will be host to more
      than half the cases of heart disease in the world within the next 15 years.
      Coronary heart disease and stroke have increased in both urban and rural areas.
      Case-control studies indicate that tobacco use, obesity with high waist:hip
      ratio, high blood pressure, high LDL cholesterol, low HDL cholesterol, abnormal
      apolipoprotein A-1:B ratio, diabetes, low consumption of fruits and vegetables,
      sedentary lifestyles and psychosocial stress are important determinants of
      cardiovascular diseases in India. These risk factors have increased substantially
      over the past 50 years and to control further escalation it is important to
      prevent them. National interventions such as increasing tobacco taxes, labelling
      unhealthy foods and trans fats, reduction of salt in processed foods and better
      urban design to promote physical activity may have a wide short-term impact.

PMID- 18083950
TI  - Intraoperative assessment of coronary grafts with fluorescent angiography.

PMID- 18083951
TI  - A case of asymptomatic high-grade aortic coarctation.

PMID- 18083952
TI  - Gene therapy: targeting the myocardium.
AB  - Effective clinical delivery of gene therapy to the heart requires understanding
      and design of complex biological systems to deliver therapeutic gene expression.
      The development of vectors that specifically target the myocardium, in particular
      bioengineered recombinant viruses, has improved the efficiency of gene delivery
      to the heart. These tools, coupled with advances in selection and design of the
      genetic payload, have led to effective cardiac gene therapy in preclinical
      models. This technology is currently translating to the clinic with a new wave of
      gene therapy trials for myocardial disease.

PMID- 18083953
TI  - Long-term results after PFO closure.

PMID- 18083954
TI  - Upgrading from right ventricular pacing to biventricular pacing in pacemaker
      patients with chronic heart failure: Heart failure.

PMID- 18083955
TI  - Women and coronary disease.

PMID- 18083956
TI  - Cardiac tumours: an update: Cardiac tumours.

PMID- 18083957
TI  - How good are the ADHD screening items of the K-SADS-PL at identifying adolescents
      with and without ADHD?

PMID- 18083958
TI  - Including blood lead levels of all immigrant children when evaluating for ADHD.

PMID- 18083959
TI  - Interpersonal coping among boys with ADHD.
AB  - OBJECTIVE: The authors investigate self-reported coping with interpersonal
      stressors among boys with and without ADHD in two studies and provide initial
      evidence for effects of different subgroups of ADHD on coping in Study 2. METHOD:
      In Study 1, 20 Austrian adolescents with ADHD were compared to 20 healthy
      controls. In Study 2, 44 German children and adolescents with ADHD (35 without
      and 9 with conduct disorders) were compared to 44 healthy controls matched by age
      and grade level, respectively. RESULTS: Increased maladaptive coping was found in
      both studies. Study 2 revealed heightened maladaptive coping among both subgroups
      of ADHD, but the subgroup of ADHD with conduct disorders was more affected
      compared to healthy controls than the subgroup with ADHD alone. CONCLUSION:
      Results suggest an impaired interpersonal coping style in ADHD and point to the
      potential benefit of stress management and social skills training for boys with
      ADHD. (

PMID- 18083960
TI  - Duration of sleep and ADHD tendency among adolescents in China.
AB  - OBJECTIVE: This study investigates the association between duration of sleep and
      ADHD tendency among adolescents. METHOD: This population-based health survey uses
      a two-stage random cluster sampling design. Participants ages 13 to 17 are
      recruited from the total population of adolescents attending high school in one
      city of China. Duration of sleep is measured by self-reported time to bed and
      rise. ADHD tendency is assessed via a structured personal interview. Data are
      analyzed using linear regression modeling with adjustment for the effects of
      cluster sampling. RESULTS: There is a highly significant and negative association
      between duration of sleep and ADHD tendency ( t = -4.99, p < .001) with a
      regression coefficient of -0.73 after adjusting for the potential confounding
      factors. CONCLUSION: Duration of sleep is associated with ADHD tendency among
      adolescents. It would be prudent for clinicians to include the assessment of
      sleep problems, including lack of sleep, in evaluating potential ADHD patients
      for treatment programs.

PMID- 18083961
TI  - Reliability, validity, and utility of instruments for self-report and informant
      report concerning symptoms of ADHD in adult patients.
AB  - OBJECTIVE: To study the correlation between symptoms of ADHD in adults, obtained
      with different methods and from different sources. METHOD: Information was
      obtained from 120 adults with ADHD, their partners, and their parents, using the
      ADHD Rating Scale, the Conners' Adult ADHD Rating Scales (CAARS), the Brown
      Attention-Deficit Disorder Scale (BADDS), and the structured interview Diagnostic
      Interview Schedule-IV, section L (DIS-L). RESULTS: All self-report rating scales
      can be used to assess ADHD symptoms in clinical samples of adults. The BADDS and
      the ADHD Rating Scale proved best in predicting the clinical diagnosis. The DSM
      IV factors, originally developed for children, achieve lower patient-informant
      agreement than the other factors. CONCLUSION: Adults with ADHD appear to be the
      best informants with regard to their symptoms but tend to underreport the
      severity of their symptoms. Informant report may be used to get additional
      information on symptoms and impairment.

PMID- 18083962
TI  - Biological bulletin virtual symposium: the neuroecology of chemical defense.

PMID- 18083963
TI  - Neuroecology, chemical defense, and the keystone species concept.
AB  - Neuroecology unifies principles from diverse disciplines, scaling from
      biophysical properties of nerve and muscle cells to community-wide impacts of
      trophic interactions. Here, these principles are used as a common fabric, woven
      from threads of chemosensory physiology, behavior, and population and community
      ecology. The "keystone species" concept, for example, is seminal in ecological
      theory. It defines a species whose impacts on communities are far greater than
      would be predicted from its relative abundance and biomass. Similarly,
      neurotoxins could function in keystone roles. They are rare within natural
      habitats but exert strong effects on species interactions at multiple trophic
      levels. Effects of two guanidine alkaloids, tetrodotoxin (TTX) and saxitoxin
      (STX), coalesce neurobiological and ecological perspectives. These molecules
      compose some of the most potent natural poisons ever described, and they are
      introduced into communities by one, or only a few, host species. Functioning as
      voltage-gated sodium channel blockers for nerve and muscle cells, TTX and STX
      serve in chemical defense. When borrowed by resistant consumer species, however,
      they are used either in chemical defense against higher order predators or for
      chemical communication as chemosensory excitants. Cascading effects of the
      compounds profoundly impact community-wide attributes, including species
      compositions and rates of material exchange. Thus, a diverse array of
      physiological traits, expressed differentially across many species, renders TTX
      and STX fully functional as keystone molecules, with vast ecological consequences
      at multiple trophic levels.

PMID- 18083964
TI  - Chemical defenses: from compounds to communities.
AB  - Marine natural products play critical roles in the chemical defense of many
      marine organisms and in some cases can influence the community structure of
      entire ecosystems. Although many marine natural products have been studied for
      biomedical activity, yielding important information about their biochemical
      effects and mechanisms of action, much less is known about ecological functions.
      The way in which marine consumers perceive chemical defenses can influence their
      health and survival and determine whether some natural products persist through a
      food chain. This article focuses on selected marine natural products, including
      okadaic acid, brevetoxins, lyngbyatoxin A, caulerpenyne, bryostatins, and
      isocyano terpenes, and examines their biosynthesis (sometimes by symbiotic
      microorganisms), mechanisms of action, and biological and ecological activity. We
      selected these compounds because their impacts on marine organisms and
      communities are some of the best-studied among marine natural products. We
      discuss the effects of these compounds on consumer behavior and physiology, with
      an emphasis on neuroecology. In addition to mediating a variety of trophic
      interactions, these compounds may be responsible for community-scale ecological
      impacts of chemically defended organisms, such as shifts in benthic and pelagic
      community composition. Our examples include harmful algal blooms; the invasion of
      the Mediterranean by Caulerpa taxifolia; overgrowth of coral reefs by chemically
      rich macroalgae and cyanobacteria; and invertebrate chemical defenses, including
      the role of microbial symbionts in compound production.

PMID- 18083965
TI  - How do predators cope with chemically defended foods?
AB  - Many prey species (including plants) deter predators with defensive chemicals.
      These defensive chemicals act by rendering the prey's tissues noxious, toxic, or
      both. Here, I explore how predators cope with the presence of these chemicals in
      their diet. First, I describe the chemosensory mechanisms by which predators
      (including herbivores) detect defensive chemicals. Second, I review the
      mechanisms by which predators either avoid or tolerate defensive chemicals in
      prey. Third, I examine how effectively free-ranging predators can overcome the
      chemical defenses of prey. The available evidence indicates that predators have
      mixed success overcoming these defenses. This conclusion is based on reports of
      free-ranging predators rejecting unpalatable but harmless prey, or voluntarily
      ingesting toxic prey.

PMID- 18083966
TI  - Has vertebrate chemesthesis been a selective agent in the evolution of arthropod
      chemical defenses?
AB  - Arthropods use a variety of chemical substances to repel potential predators, but
      how did they arrive at the suite of chemicals that they use? One way to explore
      this question is to map chemically defended arthropod species in a
      multidimensional "compound" space. Clustering within this space indicates species
      that share similar combinations of chemical compounds and can reflect a
      phylogenetic signal, common biochemical pathways, or both. More important for
      this study, clustering can help to identify allomone targets. We herein compare
      common arthropod allomones with known vertebrate trigeminal irritants. We argue
      that the degree of overlap between these two groups of compounds indicates that
      chemesthesis was an important determining factor in the evolution of many
      arthropod allomones. The multidimensional scaling methods used may also allow the
      identification of new irritant receptors.

PMID- 18083967
TI  - Escape by inking and secreting: marine molluscs avoid predators through a rich
      array of chemicals and mechanisms.
AB  - Inking by marine molluscs such as sea hares, cuttlefish, squid, and octopuses is
      a striking behavior that is ideal for neuroecological explorations. While inking
      is generally thought to be used in active defense against predators, experimental
      evidence for this view is either scant or lacks mechanistic explanations. Does
      ink act through the visual or chemical modality? If inking is a chemical defense,
      how does it function and how does it affect the chemosensory systems of
      predators? Does it facilitate escape not only by acting directly on predators but
      also by being an alarm signal for conspecifics? This review examines these
      issues, within a broader context of passive and active chemical defensive
      secretions. It focuses on recent work on mechanisms of defense by inking in sea
      hares (Aplysia) and extends what we have learned about sea hares to other
      molluscs including the cephalopods.

PMID- 18083968
TI  - Pathogen-induced defense and innate immunity in macroalgae.
AB  - Animals and vascular plants are known to defend themselves facultatively against
      pathogens, with innate receptors mediating their resistance. Macroalgal defense
      against microorganisms, in contrast, has until recently been regarded mainly as
      constitutive. Indeed, many macroalgae appear to be chemically defended at
      constantly high levels, and this is possibly one of the reasons why the first
      evidence of pathogen-aroused resistance in a macroalga was detected only a decade
      ago. Here, I summarize the results of studies that indicate the existence of
      pathogen-activated or pathogen-induced macroalgal defense. Most indications so
      far come from molecular investigations, which revealed major functional
      similarities among the defense systems of distant macroalgal clades and the
      innate immune systems of vascular plants and metazoans. Homologies exist in the
      primary and secondary defense-activating signals, as well as in the enzymes that
      are involved and the cellular responses that are activated. This strongly
      suggests that innate immunity also exists in relatively distinct macroalgal
      clades. However, a macroalgal receptor still needs to be isolated and
      characterized, and the molecular concept of macroalgal receptor-mediated immunity
      needs to be complemented with an ecological perspective on pathogen-induced
      defense, to develop a joint neuroecological perspective on seaweed-microbe
      interactions.

PMID- 18083969
TI  - Novel embryogenesis in a nudibranch gastropod: segregation, expulsion, and
      abandonment of deeply pigmented egg cytoplasm.

PMID- 18083970
TI  - Granular chitin in the epidermis of nudibranch molluscs.
AB  - Chitin is usually found in stiff extracellular coatings typified by the arthropod
      exoskeleton, and is not associated with the soft, flexible mollusc skin. Here, we
      show, however, that chitin in nudibranch gastropods (Opisthobranchia, Mollusca)
      occurs as intracellular granules that fill the epidermal cells of the skin and
      the epithelial cells of the stomach. In response to nematocysts fired by
      tentacles of prey Cnidaria, the epidermal cells of eolid nudibranchs (Aeolidacea)
      release masses of chitin granules, which then form aggregates with the nematocyst
      tubules, having the effect of insulating the animal from the deleterious action
      of the Cnidaria tentacles. Granular chitin, while protecting the animal, does not
      interfere with the suppleness and flexibility of the skin, in contrast to the
      stiffness of chitin armor. The specialized epidermis enables nudibranchs to live
      with and feed on Cnidaria.

PMID- 18083971
TI  - Role of maternal provisioning in controlling interpopulation variation in
      hatching size in the marine snail Nucella ostrina.
AB  - This study examined the role of maternal provisioning in controlling
      interpopulation variation in hatching size in nine isolated populations of the
      intertidal gastropod Nucella ostrina, in which development to the early juvenile
      stage takes place within an egg capsule. Variation among populations was almost
      entirely due to the ratio of nurse eggs to embryo, which explained 65% of the
      variation in hatching size. Egg size was not a significant predictor of hatching
      size. Differences among seven of these populations in the nurse egg/embryo ratio
      were entirely due to the number of nurse eggs allocated per capsule; these
      populations allocated different numbers of nurse eggs per capsule but allocated
      the same number of embryos. Intriguingly, the two most wave-sheltered populations
      allocated significantly more nurse eggs and more embryos to each capsule than did
      the seven other populations, but they maintained nurse egg/embryo ratios
      consistent with patterns observed in the other populations. Inter- and
      intrapopulation variation in hatching size appears to be controlled largely by
      different mechanisms: within-population variation being controlled mainly by
      differences in allocation of embryos per capsule, whereas most among-population
      variation being due to differences in allocation of nurse eggs per capsule.

PMID- 18083972
TI  - Endostyle cell recruitment as a frame of reference for development and growth in
      the Urochordate Oikopleura dioica.
AB  - In models of growth and life history, and in molecular and cell biology, there is
      a need for more accurate frames of reference to characterize developmental
      progression. In Caenorhabditis elegans, complete fate maps of cell lineage
      provide such a standard of reference. To be more widely applicable, reference
      frames should be easier to measure while still providing strong predictive
      capacity. Towards this aim, we have analyzed growth of the endostyle in the
      appendicularian Oikopleura dioica at the cellular level, and measured its
      response to temperature and food availability. Specifically, we test the
      hypothesis that age of a specific developmental stage in O. dioica can be
      predicted from the number of endostyle cells and temperature. We show that the
      endostyle grows by recruiting cells from the posterior tip into the lateral arms
      of the organ in an anterior-posterior orientation and that the rate of increase
      in lateral arm endostyle cells is temperature-dependent but unresponsive to
      nutritional intake. Endostyle cells therefore serve as an accurate and easily
      measured marker to describe developmental progression. Conceptually, such a
      method of characterizing developmental progression should help bridge life
      history events and molecular mechanisms throughout organismal aging, facilitating
      cross-disciplinary understanding by providing a common experimental framework.

PMID- 18083974
TI  - Polarity determination for the CdxZn1-xS nanocombs by EELS.
AB  - Comb-like Cd(x)Zn(1-x)S nanostructures have been synthesized by one-step metallo
      organic chemical vapor deposition (MOCVD). The microstructure and composition
      were characterized by analytical transmission electron microscopy (TEM). The
      ribbon of the comb-like structure is along [2-1-10] (the a-axis), and the
      nanotips are along [0001] (the c-axis). The atomic location by channeling
      enhanced microanalysis (ALCHEMI) technique was used to determine the polarity of
      the crystal via electron energy-loss spectroscopy (EELS). The thickness
      dependence, delocalization and beam convergent effect are discussed here. The
      investigations reveal that the growth mechanism is consistent with the asymmetric
      growth.

PMID- 18083975
TI  - Sample preparation of GaN-based materials on a sapphire substrate for STEM
      analysis.
AB  - In this work, a detailed TEM sample preparation recipe based on a wedge polishing
      technique for GaN-based materials is presented. The obtained samples have
      atomically flat surfaces without any obvious surface damages such as the
      formation of amorphous layers. A composition estimation of Al(x)Ga(1-x)N from Z
      contrast STEM imaging is carried out using these samples. The results are in good
      accord with the nominal composition.

PMID- 18083976
TI  - Ultrastructural alterations during embryonic rats' lung development caused by
      ozone.
AB  - Ozone (O3) is an oxidizing agent that acts on phospholipids, proteins and sugars
      of cellular membranes producing free radicals, which cause oxidative damages. The
      O3 exposure has been used as a model to study oxidative stress, in which the
      respiratory airways represent the entrance to the organism. In this study,
      ultrastructural alterations were identified at the bronchiolar level during the
      intra-uterine lung development, using an O3 exposure model in pregnant rats
      during 18, 20 and 21 days of gestation. Twelve pregnant Wistar rats, six controls
      and six exposed to 1 ppm O3 inhalation during 12 h per day, were used. The rats
      were sacrificed at gestational days 18, 20 and 21; the fetuses were obtained and
      their lungs dissected. The ultrastructural analysis evidenced swollen
      mitochondria, cytoplasmic vacuolization of the epithelial cells and structural
      disorder caused by the oxidative stress. At gestation day 20, flake-off
      epithelial cells and laminar bodies in the bronchiolar lumen were observed. In
      the 21-gestation-day group, the mitochondria were edematous and their cristae
      were disrupted by the damage caused in mitochondrial membranes.

PMID- 18083977
TI  - Ceramide regulation of nuclear protein import.
AB  - Nucleocytoplasmic trafficking is an essential and responsive cellular mechanism
      that directly affects cell growth and proliferation, and its potential to address
      metabolic challenge is incompletely defined. Ceramide is an antiproliferative
      sphingolipid found within vascular smooth muscle cells in atherosclerotic
      plaques, but its mechanism of action remains unclear. The hypothesis that
      ceramide inhibits cell growth through nuclear transport regulation was tested. In
      smooth muscle cells, exogenously supplemented ceramide inhibited classical
      nuclear protein import that involved the activation of cytosolic p38 mitogen
      activated protein kinase (MAPK). After application of SB 202190, a specific and
      potent pharmacological antagonist of p38 MAPK, sphingolipid impingement on
      nuclear transport was corrected. Distribution pattern assessments of two
      essential nuclear transport proteins, importin-alpha and Cellular Apoptosis
      Susceptibility, revealed ceramide-mediated relocalization that was reversed upon
      the addition of SB 202190. Furthermore, cell counts, nuclear cyclin A, and
      proliferating cell nuclear antigen expression, markers of cellular proliferation,
      were diminished after ceramide treatment and effectively rescued by the addition
      of inhibitor. Together, these data demonstrate, for the first time, the
      sphingolipid regulation of nuclear import that defines and expands the adaptive
      capacity of the nucleocytoplasmic transport machinery.

PMID- 18083978
TI  - Comparison of non-selective adrenocorticolysis with mitotane or trilostane for
      the treatment of dogs with pituitary-dependent hyperadrenocorticism.
AB  - Forty-six dogs with pituitary-dependent hyperadrenocorticism were treated with
      mitotane by the non-selective adrenocorticolysis protocol and 40 were treated
      twice a day with trilostane. The treatment groups were compared by chi-squared
      tests, and survival data were analysed using Kaplan-Meier survival plots and a
      Cox proportional hazard method. The non-selective adrenocorticolysis protocol was
      very effective (89 per cent), its toxicity was moderate (24 per cent) and there
      were fewer recurrences (29 per cent) than reported with the classical selective
      adrenocorticolysis protocol (58 per cent). In a multivariate model, age and
      bodyweight at diagnosis were significantly negatively correlated with survival
      time. The median survival time of the dogs treated with trilostane twice a day
      (900 days) was longer (P=0.05) than that of the dogs treated with mitotane (720
      days).

PMID- 18083980
TI  - Prevalence of Setaria equina microfilaraemia in horses in Hungary.
AB  - Peripheral blood samples were collected randomly from 195 horses in various parts
      of Hungary, and the presence of microfilariae was evaluated by the Knott
      technique. On the basis of morphological identification 18 of the horses (9.2 per
      cent) were infected with Setaria equina, and the infection was confirmed in 10
      animals by pcr and sequencing. The level of microfilaraemia was between 1 and
      1138 larvae in 2 ml of blood. There was no correlation between the time of
      sampling or the sex of the animals (stallions versus mares) and the prevalence of
      infection, but the prevalence decreased with age. There was a significant
      association between the prevalence of microfilaraemia and the presence of still
      waters; positive samples were collected either in the region of Lake Balaton, the
      largest lake in the country, or at places with nearby ponds.

PMID- 18083979
TI  - Failure of an inactivated vaccine against porcine reproductive and respiratory
      syndrome to protect gilts against a heterologous challenge with PRRSV.
AB  - This study was designed to evaluate the efficacy of an inactivated vaccine based
      on a European-type strain of porcine reproductive and respiratory syndrome virus
      (PRRSV) against the reproductive form of the syndrome in breeding gilts, and any
      congenital disease in their piglets. Five gilts were vaccinated twice, following
      the manufacturer's instructions, before they were inseminated. Nine additional
      gilts remained unvaccinated and served as positive (five gilts) and negative
      (four gilts) controls. A European wild-type strain genetically divergent from the
      vaccine strain was used to challenge the five vaccinated and five unvaccinated
      positive control gilts at 90 days' gestation. The vaccination of the five
      seronegative gilts did not produce any clinical signs or adverse reactions.
      However, the vaccine failed to prevent the clinical signs associated with PRRSV
      infection, viraemia after the challenge and transplacental infection of their
      piglets. The reproductive performance of the vaccinated gilts was similar to that
      of the unvaccinated positive controls, and there were no statistically
      significant differences in most of the parameters tested. However, the preweaning
      mortality of the piglets born to the vaccinated gilts was significantly lower
      than that of the piglets born to the positive control gilts.

PMID- 18083981
TI  - Performance of an environmental test to detect Mycobacterium bovis infection in
      badger social groups.

PMID- 18083982
TI  - Haematology and plasma chemistry of breeding olive ridley sea turtles
      (Lepidochelys olivacea).

PMID- 18083983
TI  - Use of sustained-release moxidectin to prevent eyeworm (Thelazia callipaeda)
      infection in dogs.

PMID- 18083984
TI  - Chronic Staphylococcus aureus endometritis in a virgin gilt.

PMID- 18083985
TI  - On-farm emergency slaughter.

PMID- 18083987
TI  - Recognised veterinary practice.

PMID- 18083988
TI  - Shredding incident.

PMID- 18083989
TI  - Identifies the problems veterinary surgeons face in carrying out clinical trials.

PMID- 18083990
TI  - Time to recognise experienced unqualified nurses?

PMID- 18083991
TI  - Emergence of garden bird trichomonosis.

PMID- 18083992
TI  - AAPL Practice Guideline for the forensic psychiatric evaluation of competence to
      stand trial.
AB  - Competence to stand trial is a legal construct used to identify those criminal
      defendants who have the requisite mental capacity to understand the nature and
      objective of the proceedings against them and to participate rationally in
      preparing their defense. This Practice Guideline has described how psychiatrists
      should evaluate individuals concerning their competence to stand trial. The
      Guideline describes acceptable forensic psychiatric practice for such
      evaluations. Where possible, it specifies standards of practice and principles of
      ethics and also emphasizes the importance of analyzing an individual defendant's
      case in the context of statutes and case law applicable in the jurisdiction where
      the evaluation takes place. The recommendations in the Guideline both reflect and
      are limited by evolving case law, statutory requirements, legal publications, and
      the current state of psychiatric knowledge. The authors have taken note of
      nationally applicable case law, federal constitutional standards, statutory
      language, and federal and state interpretations of the rights or statutes,
      recognizing that jurisdictions may differ in their specific interpretation or
      application of statutes or general constitutional standards. The review of cases
      concerning specific psychiatric diagnoses illustrates general U.S. trends, and
      psychiatrists must remain cognizant of their jurisdictions' interpretations of
      statutes or constitutional requirements. By surveying a variety of practices and
      approaches to data gathering and case analysis, the authors believe that this
      Guideline will stimulate additional collegial discussion about what is necessary
      and sufficient for adequate evaluations of adjudicative competence. The notion
      that psychiatrists should apply expertise to competence assessments stems from
      the principal that, before allowing a defendant to face criminal prosecution and
      possible punishment, courts need reasonable assurance--based, if necessary, on a
      careful, individualized evaluation--that the defendant has adequate mental
      capacity to make a defense. At a minimum, a psychiatrist's opinion about
      adjudicative competence should reflect an understanding of the jurisdictional
      standard and of how the defendant's mental condition affects competence as
      defined with the jurisdiction. The psychiatrist's report should clearly describe
      the opinion and the reasoning that leads to it. Psychiatrists who provide mental
      health expertise concerning adjudicative competence give trial courts information
      needed to assure that defendants can appropriately protect themselves and that
      criminal proceedings will be accurate, dignified,and just.

PMID- 18083993
TI  - Influence of the way results are presented on research interpretation and medical
      decision making: the PRIMER collaboration randomized studies.
AB  - BACKGROUND: The manner of presentation of research results may affect how
      clinicians interpret research and make clinical decisions. The authors evaluate
      whether the use of confidence levels improve research interpretation and decision
      making compared with P values and 95% confidence intervals. METHODS: The 2
      Presentation and Interpretation of Medical Research (PRIMER) studies were 3-arm
      randomized trials. PRIMER 1 presented results of 5 fictitious scenarios with P
      values (P), P plus 95% confidence intervals (P + CI), or P, CI, and confidence
      levels (P + CI + CL); PRIMER 2 compared P + CI + CL, P + CI, and P + CL.
      Clinicians were asked to identify the correct interpretation of scenarios in
      terms of statistical and clinical significance and then indicate the intended
      decision making in terms of treatment recommendation. RESULTS: Seventy-five and
      246 clinicians participated in PRIMER 1 and PRIMER 2, respectively. In PRIMER 1,
      P+CI+CL was superior to P + CI and P (P < 0.05); the latter 2 arms did not differ
      significantly. Decision making was not significantly different between arms. In
      PRIMER 2, P+CI+CL resulted in better interpretation than P + CI (P = 0.03), with
      no difference between P + CI and P + CL. In combined analysis, the odds of
      correct interpretation were higher for P+CI+CL than P+CI (odds ratio = 1.73,
      P=0.005, 95% CI= 1.19--2.52). Decision making was better for P + CI+ CL (P =
      0.03). On multivariate analysis, the P + CI+ CL arm and clinicians with
      statistics training, not in private practice, or participating in PRIMER 1 had
      better interpretation. The P + CI+ CL arm was the only factor improving decision
      making. CONCLUSIONS: Presenting research with a combination of P values,
      confidence intervals, and confidence levels leads to better interpretation and
      decision making by clinicians.

PMID- 18083994
TI  - Pathways through the nose for nasal intubation: a comparison of three
      endotracheal tubes.
AB  - BACKGROUND: In nasotracheal intubation, there are two main pathways in the
      nostril through which the endotracheal tube may pass. The lower pathway lies
      along the floor of the nose underneath the inferior turbinate. The upper pathway
      lies above the inferior turbinate, just below the middle turbinate. The lower
      pathway may be considered to be the safer route as it is located away from the
      middle turbinate and cribiform plate. METHODS: We conducted a randomized
      controlled trial comparing the frequency with which preformed, reinforced, and
      thermosoftened preformed tubes pass through upper and lower pathways. Ninety-two
      maxillofacial patients requiring nasotracheal intubation as part of their
      anaesthetic management were studied. Two patients were excluded from the study at
      endoscopy because of atypical nasal anatomy. After the induction of general
      anaesthesia, a standardized traditional nasal intubation was performed with a
      Macintosh laryngoscope, the operators endeavouring to direct the tube along the
      floor of the nose. Fibreoptic nasendoscopy was then performed by passing the tip
      of the fibrescope 2-3 cm into the nasal cavity above and below the tube, to
      identify the pathway taken. RESULTS: Data were analysed on 30 patients in each
      group. Five (16.7%) preformed tubes, 17 (56.7%) reinforced tubes, and 6 (20%)
      thermosoftened preformed tubes passed through the lower pathway. Significantly
      more reinforced tubes took the preferred pathway (P=0.001). Tubes passing through
      the upper pathway caused significantly more epistaxis than tubes passing through
      the lower pathway (P=0.003). CONCLUSIONS: Endotracheal tubes, particularly
      preformed tubes, frequently take the less favourable pathway during nasotracheal
      intubation, in spite of specific attempts to avoid this.

PMID- 18083995
TI  - Comparison of measured and calculated spatial dose distributions for a bench-mark
      106Ru/106Rh hot particle source.
AB  - This study is a part of a programme of research to provide validated dose
      measurement and calculation techniques for beta emitting hot particles by the
      construction of well-defined model hot particle sources. This enables parallel
      measurements and calculations to be critically compared. This particular study
      concentrates on the high-energy beta emitter, (106)Ru/(106)Rh (Emax = 3.54 MeV).
      This source is a common constituent of failed nuclear fuel, particularly in
      accident situations. The depth dose distributions were measured using
      radiochromic dye film (RDF); an imaging photon detector coupled to an LiF
      thermoluminescent dosemeter (LiF-IPD) and an extrapolation ionisation chamber
      (ECH). Dose calculations were performed using the Monte Carlo radiation transport
      code MCNP4C. Doses were measured and calculated as average values over various
      areas and depths. Of particular interest are the doses at depths of 7 and 30-50
      mg cm(-2), and averaged over an area of 1 cm2, as recommended by the
      International Commission on Radiological Protection for use in routine and
      accidental over-exposures of the skin. In this case, the average ratios
      (MCNP/measurement) for RDF, ECH and LiF-IPD were 1.07 +/- 0.02, 1.02 +/- 0.01 and
      0.83 +/- 0.16, respectively. There are significantly greater discrepancies
      between the ECH and LiF-IPD measurement techniques and calculations-particularly
      for shallow depths and small averaging areas.

PMID- 18083996
TI  - Population dose from indoor gamma exposure in the dwellings around Kudankulam
      nuclear power plant.
AB  - To assess the population dose due to the natural background radiation around the
      upcoming Kudankulam nuclear power plant, a systematic investigation has been
      carried out by measuring the indoor gamma dose. In total, 159 dwellings have been
      selected around the Kudankulam nuclear power plant area i.e. in Radhapuram and
      Nanguneri taluk (sub-districts) for the measurement. The geometric mean value of
      indoor gamma dose rate is 305 +/- 48 nGy h(-1) and 273 +/- 50 nGy h(-1) in
      Radhapuram and Nanguneri taluks (sub-districts), respectively. The annual
      effective dose due to indoor gamma radiation to the population has been found to
      be 1.5 mSv and 1.36 mSv in Radhapuram and Nanguneri taluks, respectively.

PMID- 18083997
TI  - Uncertainty on faecal analysis on dose assessment.
AB  - Monitoring programmes for internal dose assessment may need to have a combination
      of bioassay techniques, e.g. urine and faecal analysis, especially in workplaces
      where compounds of different solubilities are handled and also in cases of
      accidental intakes. Faecal analysis may be an important data for assessment of
      committed effective dose due to exposure to insoluble compounds, since the
      activity excreted by urine may not be detectable, unless a very sensitive
      measurement system is available. This paper discusses the variability of the
      daily faecal excretion based on data from just one daily collection; collection
      during three consecutive days: samples analysed individually and samples analysed
      as a pool. The results suggest that just 1 d collection is not appropriate for
      dose assessment, since the 24 h uranium excretion may vary by a factor of 40. On
      the basis of this analysis, the recommendation should be faecal collection during
      three consecutive days, and samples analysed as a pool, it is more economic and
      faster.

PMID- 18083998
TI  - Electric emissions from electrical appliances.
AB  - Electric emissions from electric appliances are frequently considered negligible,
      and standards consider electric appliances to comply without testing. By
      investigating 122 household devices of 63 different categories, it could be shown
      that emitted electric field levels do not justify general disregard. Electric
      reference values can be exceeded up to 11-fold. By numerical dosimetry with
      homogeneous human models, induced intracorporal electric current densities were
      determined and factors calculated to elevate reference levels to accounting for
      reduced induction efficiency of inhomogeneous fields. These factors were found
      not high enough to allow generally concluding on compliance with basic
      restrictions without testing. Electric appliances usually simultaneously emit
      both electric and magnetic fields exposing almost the same body region. Since the
      sum of induced current densities is limited, one field component reduces the
      available margin for the other. Therefore, superposition of electric current
      densities induced by either field would merit consideration.

PMID- 18083999
TI  - Developmental fate determination and marker discovery in hematopoietic stem cell
      biology using proteomic fingerprinting.
AB  - In hematopoiesis, co-expression of Sca-1 and c-Kit defines cells (LS(+)K) with
      long term reconstituting potential. In contrast, poorly characterized LS(-)K
      cells fail to reconstitute lethally irradiated recipients. Relative
      quantification mass spectrometry and transcriptional profiling were used to
      characterize LS(+)K and LS(-)K cells. This approach yielded data on >1200
      proteins. Only 32% of protein changes correlated to mRNA modulation demonstrating
      post-translational protein regulation in early hematopoietic development. LS(+)K
      cells had lower expression of protein synthesis proteins but did express proteins
      associated with mature cell function. Major increases in erythroid development
      proteins were observed in LS(-)K cells; based on this assessment of erythroid
      potential we showed them to be principally erythroid progenitors, demonstrating
      effective use of discovery proteomics for definition of primitive cells.

PMID- 18084000
TI  - Comment on: An allograft inflammatory factor 1 (AIF1) single nucleotide
      polymorphism (SNP) is associated with anticentromere antibody positive systemic
      sclerosis.

PMID- 18084001
TI  - Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: a
      challenging clinical dilemma.
AB  - Reversible posterior leucoencephalopathy syndrome (RPLS) has been increasingly
      recognized and reported in the literature. While the condition has been well
      described in patients with acute hypertension, pre-eclampsia, eclampsia, post
      transplantation and chemotherapy, RPLS has been increasingly identified in
      patients with autoimmune diseases such as systemic lupus erythematosus (SLE).
      Though experience in the diagnosis and management of RPLS in patients with SLE is
      likely accumulating, few have systematically worked out the strategy to
      distinguish RPLS from neuropsychiatric SLE (NPSLE) and lupus-related
      complications of the central nervous system (CNS). Prompt recognition of, and
      differentiation between, these conditions is essential since their clinical
      presentations substantially overlap and yet their management strategy and
      subsequent outcomes can be entirely different. Indeed, inappropriate treatment
      such as augmentation of immunosuppression may be detrimental to patients with
      RPLS. A high index of suspicion of RPLS, prompt magnetic resonance imaging of the
      brain, including diffusion imaging, exclusion of CNS infection and metabolic
      derangement, a comprehensive medication review accompanied by timely and
      aggressive control of blood pressure and seizure are keys to successful
      management of RPLS. Such treatment strategy ensures a very high chance of total
      neurological recovery in lupus patients with RPLS.

PMID- 18084002
TI  - Home parenteral nutrition--an effective and safe long-term therapy for systemic
      sclerosis-related intestinal failure.
AB  - OBJECTIVES: To examine the outcome in patients with SSc requiring parenteral
      nutrition (PN), and to compare their clinical characteristics with those of other
      SSc patients and of patients requiring PN/home parenteral nutrition (HPN) for
      other conditions. METHODS: Retrospective review of SSc and Intestinal Failure
      Unit databases at a tertiary referral centre for SSc/national unit for intestinal
      failure over a 13-yr period. RESULTS: Eight patients with SSc requiring PN during
      the study period were identified (2 males, 6 females: median age at commencement
      of PN 51 yrs, range 42-56 yrs). All patients commencing PN had bacterial
      overgrowth and malabsorption not responding to antibiotic therapy. The median
      duration of PN therapy in the eight patients was 40 months (range 0.8-192
      months). Between them the eight patients had a total of 13,851 catheter-use days
      and only two line infections (0.14/1000 catheter days), a lower rate of line
      infection than in other HPN-treated patients at Hope Hospital (0.52/1000 catheter
      days). Three patients died during the 13-yr period, none of causes related to
      their PN. Six were unable to manage their HPN regime themselves, mainly because
      of problems with hand function. CONCLUSIONS: Although patient numbers were small,
      our findings suggest that HPN can be safely and successfully used long-term in
      patients with SSc and should be considered for patients unable to maintain their
      nutritional status because of severe gastrointestinal involvement. Impaired hand
      function should not preclude SSc patients from receiving HPN: family members or
      community nurses may be trained in the care of the HPN line.

PMID- 18084005
TI  - Phorbol ester up-regulates phospholipase D1 but not phospholipase D2 expression
      through a PKC/Ras/ERK/NFkappaB-dependent pathway and enhances matrix
      metalloproteinase-9 secretion in colon cancer cells.
AB  - Despite its importance in cell proliferation and tumorigenesis, very little is
      known about the molecular mechanism underlying the regulation of phospholipase D
      (PLD) expression. PLD isozymes are significantly co-overexpressed with cancer
      marker genes in colorectal carcinoma. Phorbol 12-myristate 13-acetate (PMA)
      treatment, as a mitogenic signal in colon cancer cells, selectively increases
      PLD1 expression in transcription and post-transcription. Moreover, experiments
      using intraperitoneal injection of PMA into mice showed selective PLD1 induction
      in the intestine and lung tissues, which suggests its physiological relevance in
      vivo. Therefore, we have undertaken a detailed analysis of the effects of PMA on
      the promoter activity of PLD genes. Protein kinase C inhibitors, but not a
      protein kinase A inhibitor, were found to suppress the up-regulation of PLD1 but
      not PLD2. Dominant-negative mutants of Ras, Raf, and MEK suppressed the induction
      and activity of PLD1. Moreover, depletion of the supposedly involved proteins
      reduced the endogenous PLD1 protein level. An important role for NFkappaB as a
      downstream target of ERK in PMA-induced PLD1 induction was also demonstrated
      using the inhibitor, small interfering RNA, chromatin immunoprecipitation assay,
      and site-specific mutagenesis. Furthermore, inhibitors of these signaling
      proteins and depletion of PLD1 suppressed PMA-induced matrix metalloproteinase-9
      secretion and PLD1 induction. In conclusion, we demonstrate for the first time
      that induction of PLD1 through a protein kinase C/Ras/ERK/NFkappaB-dependent
      pathway is involved in the secretion of matrix metalloproteinase-9 in colorectal
      cancer cells.

PMID- 18084004
TI  - Acute alcohol tolerance is intrinsic to the BKCa protein, but is modulated by the
      lipid environment.
AB  - Ethanol tolerance, in which exposure leads to reduced sensitivity, is an
      important component of alcohol abuse and addiction. The molecular mechanisms
      underlying this process remain poorly understood. The BKCa channel plays a
      central role in the behavioral response to ethanol in Caenorhabditis elegans
      (Davies, A. G., Pierce-Shimomura, J. T., Kim, H., VanHoven, M. K., Thiele, T. R.,
      Bonci, A., Bargmann, C. I., and McIntire, S. L. (2003) Cell 115, 655-666) and
      Drosophila (Cowmeadow, R. B., Krishnan, H. R., and Atkinson, N. S. (2005)
      Alcohol. Clin. Exp. Res. 29, 1777-1786) . In neurons, ethanol tolerance in BKCa
      channels has two components: a reduced number of membrane channels and decreased
      potentiation of the remaining channels (Pietrzykowski, A. Z., Martin, G. E.,
      Puig, S. I., Knott, T. K., Lemos, J. R., and Treistman, S. N. (2004) J. Neurosci.
      24, 8322-8332) . Here, heterologous expression coupled with planar bilayer
      techniques examines two additional aspects of tolerance in human BKCa channels.
      1) Is acute tolerance observed in a single channel protein complex within a lipid
      environment reduced to only two lipids? 2) Does lipid bilayer composition affect
      the appearance of acute tolerance? We found that tolerance was observable in BKCa
      channels in membrane patches pulled from HEK cells and when they are placed into
      reconstituted 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine/1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine membranes. Furthermore,
      altering bilayer thickness by incorporating the channel into lipid mixtures of
      1,2-dioleoyl-3-phosphatidylethanolamine with phosphatidylcholines of increasing
      chain length, or with sphingomyelin, strongly affected the sensitivity of the
      channel, as well as the time course of the acute response. Ethanol sensitivity
      changed from a strong potentiation in thin bilayers to inhibition in thick
      sphingomyelin/1,2-dioleoyl-3-phosphatidylethanolamine bilayers. Thus, tolerance
      can be an intrinsic property of the channel protein-lipid complex, and bilayer
      thickness plays an important role in shaping the pattern of response to ethanol.
      As a consequence of these findings the protein-lipid complex should be treated as
      a unit when studying ethanol action.

PMID- 18084006
TI  - Serine 88 phosphorylation of the 8-kDa dynein light chain 1 is a molecular switch
      for its dimerization status and functions.
AB  - Dynein light chain 1 (DLC1, also known as DYNLL1, LC8, and PIN), a ubiquitously
      expressed and highly conserved protein, participates in a variety of essential
      intracellular events. Transition of DLC1 between dimer and monomer forms might
      play a crucial role in its function. However, the molecular mechanism(s) that
      control the transition remain unknown. DLC1 phosphorylation on Ser(88) by p21
      activated kinase 1 (Pak1), a signaling nodule, promotes mammalian cell survival
      by regulating its interaction with Bim and the stability of Bim. Here we
      discovered that phosphorylation of Ser(88), which juxtapose each other at the
      interface of the DLC dimer, disrupts DLC1 dimer formation and consequently
      impairs its interaction with Bim. Overexpression of a Ser(88) phosphorylation
      inactive DLC1 mutant in mammary epithelium cells and in a transgenic animal model
      caused apoptosis and accelerated mammary gland involution, respectively, with
      increased Bim levels. Structural and biophysical studies suggested that
      phosphorylation-mimicking mutation leads to dissociation of the DLC1 dimer to a
      pure folded monomer. The phosphorylation-induced DLC1 monomer is incapable of
      binding to its substrate Bim. These findings reveal a previously unrecognized
      regulatory mechanism of DLC1 in which the Ser(88) phosphorylation acts as a
      molecular switch for the transition of DLC1 from dimer to monomer, thereby
      modulating its interaction with substrates and consequently regulating the
      functions of DLC1.

PMID- 18084007
TI  - Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid
      induced leucine zipper (GILZ).
AB  - Mesenchymal stem cells (MSCs) can differentiate into multiple cell lineages,
      including osteoblasts and adipocytes. We reported previously that glucocorticoid
      induced leucine zipper (GILZ) inhibits peroxisome proliferator-activated receptor
      gamma-2 (Ppargamma2) expression and blocks adipocyte differentiation. Here we
      show that overexpression of GILZ in mouse MSCs, but not MC3T3-E1 osteoblasts,
      increases alkaline phosphatase activity and enhances mineralized bone nodule
      formation, whereas knockdown of Gilz reduces MSC osteogenic differentiation
      capacity. Consistent with these observations, real-time reverse transcription-PCR
      analysis showed that both basal and differentiation-induced transcripts of the
      lineage commitment gene Runx2/Cbfa1, as well as osteoblast differentiation marker
      genes including alkaline phosphatase, type I collagen, and osteocalcin, were all
      increased in GILZ-expressing cells. In contrast, the mRNA levels of adipogenic
      Ppargamma2 and C/ebpalpha were significantly reduced in GILZ-expressing cells
      under both osteogenic and adipogenic conditions. Together, our results
      demonstrate that GILZ functions as a modulator of MSCs and that overexpression of
      GILZ shifts the balance between osteogenic and adipogenic differentiation of MSCs
      toward the osteogenic pathway. These data suggest that GILZ may have therapeutic
      value for stem cell-based therapies of metabolic bone diseases, such as fracture
      repair.

PMID- 18084008
TI  - Monitoring late-onset toxicities in phase I trials using predicted risks.
AB  - Late-onset (LO) toxicities are a serious concern in many phase I trials. Since
      most dose-limiting toxicities occur soon after therapy begins, most dose-finding
      methods use a binary indicator of toxicity occurring within a short initial time
      period. If an agent causes LO toxicities, however, an undesirably large number of
      patients may be treated at toxic doses before any toxicities are observed. A
      method addressing this problem is the time-to-event continual reassessment method
      (TITE-CRM, Cheung and Chappell, 2000). We propose a Bayesian dose-finding method
      similar to the TITE-CRM in which doses are chosen using time-to-toxicity data.
      The new aspect of our method is a set of rules, based on predictive
      probabilities, that temporarily suspend accrual if the risk of toxicity at
      prospective doses for future patients is unacceptably high. If additional follow
      up data reduce the predicted risk of toxicity to an acceptable level, then
      accrual is restarted, and this process may be repeated several times during the
      trial. A simulation study shows that the proposed method provides a greater
      degree of safety than the TITE-CRM, while still reliably choosing the preferred
      dose. This advantage increases with accrual rate, but the price of this
      additional safety is that the trial takes longer to complete on average.

PMID- 18084009
TI  - Toward gene therapy of primary ovarian failure: adenovirus expressing human FSH
      receptor corrects the Finnish C566T mutation.
AB  - Resistance ovarian syndrome is a heterogeneous disorder inherited as a Mendelian
      recessive trait and characterized by infertility, primary amenorrhea, normal
      karyotype and elevated serum FSH and LH levels. An inactivating mutation, C566T,
      in FSH receptor gene (FSHR) has been identified initially in Finland. We
      investigated if an adenovirus expressing a normal copy of human FSHR (Ad-hFSHR)
      has the ability to: (i) transfect granulosa cell lines, (ii) render the
      transfected cell lines responsive to FSH stimulation and (iii) transcomplement
      the malfunctioning form of human FSHR gene with C566T mutation. COS-7, JC-410, JC
      410-P450-scc-luc and JC-410-StAR-luc cell lines were infected by Ad-hFSHR
      followed by treatment with FSH. Functional activity of the Ad-hFSHR was tested by
      measuring cyclic adenosine monophosphate (cAMP) or luciferase activity in
      response to FSH stimulation, and showed 2-4.6-fold increases in Ad-hFSHR
      transfected cells compared with untransfected or Ad-LacZ transfected cells,
      indicating that Ad-hFSHR is functionally active and expressing hFSHR. Generation
      of cAMP in cells expressing only mutated hFSHR-T566 showed minimal increase after
      FSH stimulation. Co-transfection of Ad-hFSHR in these cells carrying the
      malfunction form of human FSHR caused significant increases of 2.2-7.4-fold in
      FSH dependent cAMP generation (P = 0.0007). We concluded that adenovirus
      expressing a normal human FSHR can compensate the inactivating human FSHR-C566T
      mutation and restore FSH responsiveness.

PMID- 18084010
TI  - Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with
      age.
AB  - Mammalian oocytes begin meiosis in the fetal ovary, but only complete it when
      fertilized in the adult reproductive tract. This review examines the cell biology
      of this protracted process: from entry of primordial germ cells into meiosis to
      conception. The defining feature of meiosis is two consecutive cell divisions
      (meiosis I and II) and two cell cycle arrests: at the germinal vesicle (GV),
      dictyate stage of prophase I and at metaphase II. These arrests are spanned by
      three key events, the focus of this review: (i) passage from mitosis to GV arrest
      during fetal life, regulated by retinoic acid; (ii) passage through meiosis I and
      (iii) completion of meiosis II following fertilization, both meiotic divisions
      being regulated by cyclin-dependent kinase (CDK1) activity. Meiosis I in human
      oocytes is associated with an age-related high rate of chromosomal mis
      segregation, such as trisomy 21 (Down's syndrome), resulting in aneuploid
      conceptuses. Although aneuploidy is likely to be multifactorial, oocytes from
      older women may be predisposed to be becoming aneuploid as a consequence of an
      age-long decline in the cohesive ties holding chromosomes together. Such loss
      goes undetected by the oocyte during meiosis I either because its ability to
      respond and block division also deteriorates with age, or as a consequence of
      being inherently unable to respond to the types of segregation defects induced by
      cohesion loss.

PMID- 18084012
TI  - Capturing creativity.

PMID- 18084013
TI  - Neuronal cell death in the Sudden Infant Death Syndrome brainstem and
      associations with risk factors.
AB  - Immunoreactive expression of three cell death markers was quantitatively analysed
      in the human infant brainstem medulla. We assessed active caspase-3, TUNEL and
      single-stranded DNA (ssDNA) in a cohort of 92 infants, and analysed for: (i)
      variations in the immunoreactive expression with development; (ii) comparison of
      infants diagnosed with the Sudden Infant Death Syndrome (SIDS, n = 67) to infants
      who died suddenly with another diagnosis (non-SIDS, n = 25); and (iii)
      correlations with known clinical risk factors for SIDS. Five nuclei from the
      brainstem medulla (caudal and rostral levels) were studied, including the
      hypoglossal (XII), dorsal motor nucleus of the vagus (DMNV), the dorsal column
      nuclei (gracile and cuneate) and the arcuate nucleus. Our main hypothesis was
      that neuronal cell death would be increased in SIDS compared to non-SIDS infants,
      and the increase would correlate with risk factors such as prone sleeping and
      cigarette smoke exposure. Comparing SIDS to non-SIDS, there was an increase in
      caspase-3 in the rostral DMNV (P = 0.01), and a trend to increased TUNEL in the
      arcuate nucleus (P = 0.1), which was statistically significant when comparing the
      male SIDS to male non-SIDS cohort (P = 0.04). No major changes for ssDNA
      immunoreactivity were found. Moreover, TUNEL expression was affected by post
      conceptional age, by sleep-related risk factors (predominantly affecting the
      dorsal column nuclei), and by cigarette smoke exposure in the rostral DMNV and
      arcuate nucleus. Active caspase-3 was affected by post-conceptional age but only
      in the XII, while gender-related differences were seen in the arcuate nucleus.
      This study provides further evidence of increased apoptosis in the brainstem of
      SIDS infants, but shows for the first time that these changes are also affected
      by age and gender, and by clinical risk factors such as the sleep position and
      cigarette smoke exposure.

PMID- 18084014
TI  - Disruption of a gene encoding C4-dicarboxylate transporter-like protein increases
      ozone sensitivity through deregulation of the stomatal response in Arabidopsis
      thaliana.
AB  - To understand better the plant response to ozone, we isolated and characterized
      an ozone-sensitive (ozs1) mutant strain from a set of T-DNA-tagged Arabidopsis
      thaliana ecotype Columbia. The mutant plants show enhanced sensitivity to ozone,
      desiccation and sulfur dioxide, but have normal sensitivity to hydrogen peroxide,
      low temperature and high light levels. The T-DNA was inserted at a single locus
      which is linked to ozone sensitivity. Identification of the genomic sequences
      flanking the T-DNA insertion revealed disruption of a gene encoding a transporter
      like protein of the tellurite resistance/C(4)-dicarboxylate transporter family.
      Plants with either of two different T-DNA insertions in this gene were also
      sensitive to ozone, and these plants failed to complement ozs1. Transpiration
      levels, stomatal conductance levels and the size of stomatal apertures were
      greater in ozs1 mutant plants than in the wild type. The stomatal apertures of
      ozs1 mutant plants responded to light fluctuations but were always larger than
      those of the wild-type plants under the same conditions. The stomata of the
      mutant and wild-type plants responded similarly to stimuli such as light,
      abscisic acid, high concentrations of carbon dioxide and ozone. These results
      suggest that OZS1 helps to close stomata, being not involved in the responses to
      these signals.

PMID- 18084015
TI  - Effects of fondaparinux in patients with ST-segment elevation acute myocardial
      infarction not receiving reperfusion treatment.
AB  - AIMS: At least one quarter of ST-segment elevation myocardial infarction (STEMI)
      patients do not receive reperfusion therapy, and these patients are at high risk
      for new ischaemic events. We evaluated fondaparinux treatment vs. usual care,
      i.e. placebo or unfractionated (UF) heparin, in a pre-specified subgroup of 2867
      (out of 12 092) patients not receiving reperfusion treatment in the OASIS-6
      trial. METHODS: In all, 1458 patients were randomized to fondaparinux 2.5 mg once
      daily subcutaneously up to 8 days and 1409 patients to usual care (control).
      Randomization was stratified by indication for UF heparin (stratum II, n = 1226)
      or not (stratum I, n = 1641) based on the investigator's judgment. RESULTS: The
      proportion of patients who suffered death or myocardial re-infarction at 30 days
      (primary outcome) was 12.2% in the fondaparinux vs. 15.1% in the control group,
      hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.65-0.98. There was no
      increase in severe bleedings, HR 0.82; CI 0.44-1.55, or strokes, HR 0.62; CI 0.29
      1.33. Consequently, the composite of death, myocardial re-infarction, or severe
      bleeding were significantly reduced at 30 days, HR 0.81; CI 0.67-0.99. Reductions
      in death or myocardial re-infarction at 30 days were consistent in stratum I with
      fondaparinux vs. placebo, HR 0.88; 95% CI 0.65-1.19, and in stratum II with
      fondaparinux vs. UF heparin infusion for 24-48 h (n = 806), HR 0.74; CI 95% 0.57
      0.97, P = 0.41 for heterogeneity. CONCLUSION: In STEMI patients not receiving
      reperfusion treatment, fondaparinux reduces the composite of death or myocardial
      re-infarction without an increase in severe bleedings or strokes as compared to
      placebo or UF heparin.

PMID- 18084016
TI  - Arterial structure and function in young adults with the metabolic syndrome: the
      Cardiovascular Risk in Young Finns Study.
AB  - AIMS: To study the relations between the metabolic syndrome (MS) and subclinical
      atherosclerosis in young adults. METHODS AND RESULTS: International Diabetes
      Federation (msIDF), National Institute of Health Adult Treatment Panel III
      (msNCEP), and European Group for the Study of Insulin Resistance (msEGIR)
      definitions of MS were related to carotid artery intima-media thickness (cIMT),
      brachial flow-mediated dilatation (FMD), and carotid artery compliance (CAC) in
      2163 Finnish adults (aged 32 +/- 5years). All definitions associated with
      increased cIMT and decreased CAC in both sexes. The cIMT values (mean+/-SD) were
      0.576 +/- 0.088 mm in subjects without the syndrome, 0.615 +/- 0.102 mm in msIDF,
      0.617 +/- 0.104 mm in msNCEP, and 0.607 +/- 0.097 mm in msEGIR (P < 0.0001).
      Corresponding CAC values were 2.26 +/- 0.72, 1.76 +/- 0.66, 1.73 +/- 0.66, 1.72
      +/- 0.66%/10 mmHg (P < 0.001). Impaired brachial FMD was not related to MS but it
      modified the relations between MS and cIMT: MS correlated with increased cIMT in
      subjects with an impaired FMD response (P = 0.003) but not in subjects with an
      enhanced FMD response (P = 0.75). CONCLUSION: All current definitions of MS
      identify a population of young adults with evidence of increased subclinical
      atherosclerosis. Impaired brachial endothelial response is not a hallmark of MS
      in young adults, but the status of endothelial function modifies the association
      between metabolic risk factors and atherosclerosis.

PMID- 18084017
TI  - Cardiac computed tomography: indications, applications, limitations, and training
      requirements: report of a Writing Group deployed by the Working Group Nuclear
      Cardiology and Cardiac CT of the European Society of Cardiology and the European
      Council of Nuclear Cardiology.
AB  - As a consequence of improved technology, there is growing clinical interest in
      the use of multi-detector row computed tomography (MDCT) for non-invasive
      coronary angiography. Indeed, the accuracy of MDCT to detect or exclude coronary
      artery stenoses has been high in many published studies. This report of a Writing
      Group deployed by the Working Group Nuclear Cardiology and Cardiac CT (WG 5) of
      the European Society of Cardiology and the European Council of Nuclear Cardiology
      summarizes the present state of cardiac CT technology, as well as the currently
      available data concerning its accuracy and applicability in certain clinical
      situations. Besides coronary CT angiography, the use of CT for the assessment of
      cardiac morphology and function, evaluation of perfusion and viability, and
      analysis of heart valves is discussed. In addition, recommendations for clinical
      applications of cardiac CT imaging are given and limitations of the technique are
      described.

PMID- 18084018
TI  - Variation in the ADIPOQ gene promoter is associated with carotid intima media
      thickness independent of plasma adiponectin levels in healthy subjects.
AB  - AIMS: The ADIPOQ gene encodes the protein adiponectin, and decreased circulating
      adiponectin levels have been observed in cardiovascular disease. We investigated
      the role of the ADIPOQ gene single-nucleotide polymorphisms (SNPs) A-11426G, G
      11391A, C-11377G, and T45G with plasma adiponectin levels and common carotid
      artery intima media thickness (IMT) in a cohort of healthy subjects participating
      in the RISC (Relationship between Insulin Sensitivity and Cardiovascular disease)
      study. METHODS AND RESULTS: Anthropometric and metabolic assessment and B-mode
      ultrasound of the carotid IMT were measured in 1306 subjects [589 men; 717 women,
      mean +/- SD age 43.8 +/- 8.3 years, BMI 25.5 +/- 4.0 kg/m(2)] recruited from 19
      centres in 14 European countries. Carriers of the -11426G allele and homozygous
      carriers of the -11391G allele had significantly lower plasma adiponectin levels.
      These relationships remained significant after adjusting for age, sex,
      recruitment centre, and BMI. Carriers of SNP -11377G allele had significantly
      greater IMT values compared with C allele homozygotes [geometric mean
      (interquartile range) 601 (543-665) vs. 590 (537-647) mum, P = 0.021]. This
      relationship became stronger after correcting for key covariates, including
      plasma adiponectin levels (P = 0.011). CONCLUSION: Variation within the ADIPOQ
      gene promoter is directly associated with carotid IMT in healthy subjects and is
      independent of circulating adiponectin levels.

PMID- 18084019
TI  - Ventricular septal defect as casual finding in non-invasive CT-angiography.

PMID- 18084020
TI  - Analysis of intermolecular base pair formation of prohead RNA of the phage phi29
      DNA packaging motor using NMR spectroscopy.
AB  - The bacteriophage o29 DNA packaging motor that assembles on the precursor capsid
      (prohead) contains an essential 174-nt structural RNA (pRNA) that forms
      multimers. To determine the structural features of the CE- and D-loops believed
      to be involved in multimerization of pRNA, 35- and 19-nt RNA molecules containing
      the CE-loop or the D-loop, respectively, were produced and shown to form a
      heterodimer in a Mg2+-dependent manner, similar to that with full-length pRNA. It
      has been hypothesized that four intermolecular base pairs are formed between pRNA
      molecules. Our NMR study of the heterodimer, for the first time, proved directly
      the existence of two intermolecular Watson-Crick G-C base pairs. The two
      potential intermolecular A-U base pairs were not observed. In addition,
      flexibility of the D-loop was found to be important since a Watson-Crick base
      pair introduced at the base of the D-loop disrupted the formation of the
      intermolecular G-C hydrogen bonds, and therefore affected heterodimerization.
      Introduction of this mutation into the biologically active 120-nt pRNA (U80C
      mutant) resulted in no detectable dimerization at ambient temperature as shown by
      native gel and sedimentation velocity analyses. Interestingly, this pRNA bound to
      prohead and packaged DNA as well as the wild-type 120-nt pRNA.

PMID- 18084021
TI  - STITCH: interaction networks of chemicals and proteins.
AB  - The knowledge about interactions between proteins and small molecules is
      essential for the understanding of molecular and cellular functions. However,
      information on such interactions is widely dispersed across numerous databases
      and the literature. To facilitate access to this data, STITCH ('search tool for
      interactions of chemicals') integrates information about interactions from
      metabolic pathways, crystal structures, binding experiments and drug-target
      relationships. Inferred information from phenotypic effects, text mining and
      chemical structure similarity is used to predict relations between chemicals.
      STITCH further allows exploring the network of chemical relations, also in the
      context of associated binding proteins. Each proposed interaction can be traced
      back to the original data sources. Our database contains interaction information
      for over 68,000 different chemicals, including 2200 drugs, and connects them to
      1.5 million genes across 373 genomes and their interactions contained in the
      STRING database. STITCH is available at http://stitch.embl.de/.

PMID- 18084022
TI  - Solution structures of 2 : 1 and 1 : 1 DNA polymerase-DNA complexes probed by
      ultracentrifugation and small-angle X-ray scattering.
AB  - We report small-angle X-ray scattering (SAXS) and sedimentation velocity (SV)
      studies on the enzyme-DNA complexes of rat DNA polymerase beta (Pol beta) and
      African swine fever virus DNA polymerase X (ASFV Pol X) with one-nucleotide
      gapped DNA. The results indicated formation of a 2 : 1 Pol beta-DNA complex,
      whereas only 1 : 1 Pol X-DNA complex was observed. Three-dimensional structural
      models for the 2 : 1 Pol beta-DNA and 1 : 1 Pol X-DNA complexes were generated
      from the SAXS experimental data to correlate with the functions of the DNA
      polymerases. The former indicates interactions of the 8 kDa 5'-dRP lyase domain
      of the second Pol beta molecule with the active site of the 1 : 1 Pol beta-DNA
      complex, while the latter demonstrates how ASFV Pol X binds DNA in the absence of
      DNA-binding motif(s). As ASFV Pol X has no 5'-dRP lyase domain, it is reasonable
      not to form a 2 : 1 complex. Based on the enhanced activities of the 2 : 1
      complex and the observation that the 8 kDa domain is not in an optimal
      configuration for the 5'-dRP lyase reaction in the crystal structures of the
      closed ternary enzyme-DNA-dNTP complexes, we propose that the asymmetric 2 : 1
      Pol beta-DNA complex enhances the function of Pol beta.

PMID- 18084023
TI  - Impaired function of the phage-type RNA polymerase RpoTp in transcription of
      chloroplast genes is compensated by a second phage-type RNA polymerase.
AB  - Although chloroplast genomes are small, the transcriptional machinery is very
      complex in plastids of higher plants. Plastidial genes of higher plants are
      transcribed by plastid-encoded (PEP) and nuclear-encoded RNA polymerases (NEP).
      The nuclear genome of Arabidopsis contains two candidate genes for NEP, RpoTp and
      RpoTmp, both coding for phage-type RNA polymerases. We have analyzed the use of
      PEP and NEP promoters in transgenic Arabidopsis lines with altered RpoTp
      activities and in Arabidopsis RpoTp insertion mutants lacking functional RpoTp.
      Low or lacking RpoTp activity resulted in an albino phenotype of the seedlings,
      which normalized later in development. Differences in promoter usage between wild
      type and plants with altered RpoTp activity were also most obvious early in
      development. Nearly all NEP promoters were used in plants with low or lacking
      RpoTp activity, though certain promoters showed reduced or even increased usage.
      The strong NEP promoter of the essential ycf1 gene, however, was not used in
      mutant seedlings lacking RpoTp activity. Our data provide evidence for NEP being
      represented by two phage-type RNA polymerases (RpoTp and RpoTmp) that have
      overlapping as well as gene-specific functions in the transcription of plastidial
      genes.

PMID- 18084024
TI  - Modulation of utrophin A mRNA stability in fast versus slow muscles via an AU
      rich element and calcineurin signaling.
AB  - We examined the role of post-transcriptional mechanisms in controlling utrophin A
      mRNA expression in slow versus fast skeletal muscles. First, we determined that
      the half-life of utrophin A mRNA is significantly shorter in the presence of
      proteins isolated from fast muscles. Direct plasmid injection experiments using
      reporter constructs containing the full-length or truncated variants of the
      utrophin 3'UTR into slow soleus and fast extensor digitorum longus muscles
      revealed that a region of 265 nucleotides is sufficient to confer lower levels of
      reporter mRNA in fast muscles. Further analysis of this region uncovered a
      conserved AU-rich element (ARE) that suppresses expression of reporter mRNAs in
      cultured muscle cells. Moreover, stability of reporter mRNAs fused to the
      utrophin full-length 3'UTR was lower in the presence of fast muscle protein
      extracts. This destabilization effect seen in vivo was lost upon deletion of the
      conserved ARE. Finally, we observed that calcineurin signaling affects utrophin A
      mRNA stability through the conserved ARE. These results indicate that ARE
      mediated mRNA decay is a key mechanism that regulates expression of utrophin A
      mRNA in slow muscle fibers. This is the first demonstration of ARE-mediated mRNA
      decay regulating the expression of a gene associated with the slow myogenic
      program.

PMID- 18084025
TI  - Genome-wide tracking of unmethylated DNA Alu repeats in normal and cancer cells.
AB  - Methylation of the cytosine is the most frequent epigenetic modification of DNA
      in mammalian cells. In humans, most of the methylated cytosines are found in CpG
      rich sequences within tandem and interspersed repeats that make up to 45% of the
      human genome, being Alu repeats the most common family. Demethylation of Alu
      elements occurs in aging and cancer processes and has been associated with gene
      reactivation and genomic instability. By targeting the unmethylated SmaI site
      within the Alu sequence as a surrogate marker, we have quantified and identified
      unmethylated Alu elements on the genomic scale. Normal colon epithelial cells
      contain in average 25 486 +/- 10 157 unmethylated Alu's per haploid genome, while
      in tumor cells this figure is 41 995 +/- 17 187 (P = 0.004). There is an inverse
      relationship in Alu families with respect to their age and methylation status:
      the youngest elements exhibit the highest prevalence of the SmaI site (AluY: 42%;
      AluS: 18%, AluJ: 5%) but the lower rates of unmethylation (AluY: 1.65%; AluS:
      3.1%, AluJ: 12%). Data are consistent with a stronger silencing pressure on the
      youngest repetitive elements, which are closer to genes. Further insights into
      the functional implications of atypical unmethylation states in Alu elements will
      surely contribute to decipher genomic organization and gene regulation in complex
      organisms.

PMID- 18084026
TI  - Comprehensive comparison of the interaction of the E2 master regulator with its
      cognate target DNA sites in 73 human papillomavirus types by sequence statistics.
AB  - Mucosal human papillomaviruses (HPVs) are etiological agents of oral, anal and
      genital cancer. Properties of high- and low-risk HPV types cannot be reduced to
      discrete molecular traits. The E2 protein regulates viral replication and
      transcription through a finely tuned interaction with four sites at the upstream
      regulatory region of the genome. A computational study of the E2-DNA interaction
      in all 73 types within the alpha papillomavirus genus, including all known
      mucosal types, indicates that E2 proteins have similar DNA discrimination
      properties. Differences in E2-DNA interaction among HPV types lie mostly in the
      target DNA sequence, as opposed to the amino acid sequence of the conserved DNA
      binding alpha helix of E2. Sequence logos of natural and in vitro selected sites
      show an asymmetric pattern of conservation arising from indirect readout, and
      reveal evolutionary pressure for a putative methylation site. Based on DNA
      sequences only, we could predict differences in binding energies with a standard
      deviation of 0.64 kcal/mol. These energies cluster into six discrete affinity
      hierarchies and uncovered a fifth E2-binding site in the genome of six HPV types.
      Finally, certain distances between sites, affinity hierarchies and their eventual
      changes upon methylation, are statistically associated with high-risk types.

PMID- 18084027
TI  - In situ oligonucleotide synthesis on carbon materials: stable substrates for
      microarray fabrication.
AB  - Glass has become the standard substrate for the preparation of DNA arrays.
      Typically, glass is modified using silane chemistries to provide an appropriate
      functional group for nucleic acid synthesis or oligonucleotide immobilization. We
      have found substantial issues with the stability of these surfaces as manifested
      in the unwanted release of oligomers from the surface when incubated in aqueous
      buffers at moderate temperatures. To address this issue, we have explored the use
      of carbon-based substrates. Here, we demonstrate in situ synthesis of
      oligonucleotide probes on carbon-based substrates using light-directed
      photolithographic phosphoramidite chemistry and evaluate the stabilities of the
      resultant DNA arrays compared to those fabricated on silanized glass slides. DNA
      arrays on carbon-based substrates are substantially more stable than arrays
      prepared on glass. This superior stability enables the use of high-density DNA
      arrays for applications involving high temperatures, basic conditions, or where
      serial hybridization and dehybridization is desired.

PMID- 18084028
TI  - The U1, U2 and U5 snRNAs crosslink to the 5' exon during yeast pre-mRNA splicing.
AB  - Activation of pre-messenger RNA (pre-mRNA) splicing requires 5' splice site
      recognition by U1 small nuclear RNA (snRNA), which is replaced by U5 and U6
      snRNA. Here we use crosslinking to investigate snRNA interactions with the 5'
      exon adjacent to the 5' splice site, prior to the first step of splicing. U1
      snRNA was found to interact with four different 5' exon positions using one
      specific sequence adjacent to U1 snRNA helix 1. This novel interaction of U1 we
      propose occurs before U1-5' splice site base pairing. In contrast, U5 snRNA
      interactions with the 5' exon of the pre-mRNA progressively shift towards the 5'
      end of U5 loop 1 as the crosslinking group is placed further from the 5' splice
      site, with only interactions closest to the 5' splice site persisting to the 5'
      exon intermediate and the second step of splicing. A novel yeast U2 snRNA
      interaction with the 5' exon was also identified, which is ATP dependent and
      requires U2-branchpoint interaction. This study provides insight into the nature
      and timing of snRNA interactions required for 5' splice site recognition prior to
      the first step of pre-mRNA splicing.

PMID- 18084029
TI  - The translation of recombinant proteins in E. coli can be improved by in silico
      generating and screening random libraries of a -70/+96 mRNA region with respect
      to the translation initiation codon.
AB  - Recombinant protein translation in Escherichia coli may be limited by stable
      (i.e. low free energy) secondary structures in the mRNA translation initiation
      region. To circumvent this issue, we have set-up a computer tool called 'ExEnSo'
      (Expression Enhancer Software) that generates a random library of 8192 sequences,
      calculates the free energy of secondary structures of each sequence in the 
      70/+96 region (base 1 is the translation initiation codon), and then selects the
      sequence having the highest free energy. The software uses this 'optimized'
      sequence to create a 5' primer that can be used in PCR experiments to amplify the
      coding sequence of interest prior to sub-cloning into a prokaryotic expression
      vector. In this article, we report how ExEnSo was set-up and the results obtained
      with nine coding sequences with low expression levels in E. coli. The free energy
      of the -70/+96 region of all these coding sequences was increased compared to the
      non-optimized sequences. Moreover, the protein expression of eight out of nine of
      these coding sequences was increased in E. coli, indicating a good correlation
      between in silico and in vivo results. ExEnSo is available as a free online tool.

PMID- 18084030
TI  - Developmentally regulated cleavage of tRNAs in the bacterium Streptomyces
      coelicolor.
AB  - The ability to sense and respond to environmental and physiological signals is
      critical for the survival of the soil-dwelling Gram-positive bacterium
      Streptomyces coelicolor. Nutrient deprivation triggers the onset of a complex
      morphological differentiation process that involves the raising of aerial hyphae
      and formation of spore chains, and coincides with the production of a diverse
      array of clinically relevant antibiotics and other secondary metabolites. These
      processes are tightly regulated; however, the genes and signals involved have not
      been fully elucidated. Here, we report a novel tRNA cleavage event that follows
      the same temporal regulation as morphological and physiological differentiation,
      and is growth medium dependent. All tRNAs appear to be susceptible to cleavage;
      however, there appears to be a bias towards increased cleavage of those tRNAs
      that specify highly utilized codons. In contrast to what has been observed in
      eukaryotes, accumulation of tRNA halves in S. coelicolor is not significantly
      affected by amino acid starvation, and is also not affected by induction of the
      stringent response or inhibition of ribosome function. Mutants defective in
      aerial development and antibiotic production exhibit altered tRNA cleavage
      profiles relative to wild-type strains.

PMID- 18084031
TI  - From micrograms to picograms: quantitative PCR reduces the material demands of
      high-throughput sequencing.
AB  - Current efforts to recover the Neandertal and mammoth genomes by 454 DNA
      sequencing demonstrate the sensitivity of this technology. However, routine 454
      sequencing applications still require microgram quantities of initial material.
      This is due to a lack of effective methods for quantifying 454 sequencing
      libraries, necessitating expensive and labour-intensive procedures when
      sequencing ancient DNA and other poor DNA samples. Here we report a 454
      sequencing library quantification method based on quantitative PCR that
      effectively eliminates these limitations. We estimated both the molecule numbers
      and the fragment size distributions in sequencing libraries derived from
      Neandertal DNA extracts, SAGE ditags and bonobo genomic DNA, obtaining optimal
      sequencing yields without performing any titration runs. Using this method, 454
      sequencing can routinely be performed from as little as 50 pg of initial material
      without titration runs, thereby drastically reducing costs while increasing the
      scope of sample throughput and protocol development on the 454 platform. The
      method should also apply to Illumina/Solexa and ABI/SOLiD sequencing, and should
      therefore help to widen the accessibility of all three platforms.

PMID- 18084032
TI  - Site specific phosphorylation of yeast RNA polymerase I.
AB  - All nuclear RNA polymerases are phosphoprotein complexes. Yeast RNA polymerase I
      (Pol I) contains approximately 15 phosphate groups, distributed to 5 of the 14
      subunits. Information about the function of the single phosphosites and their
      position in the primary, secondary and tertiary structure is lacking. We used a
      rapid and efficient way to purify yeast RNA Pol I to determine 13 phosphoserines
      and -threonines. Seven of these phosphoresidues could be located in the 3D
      homology model for Pol I, five of them are more at the surface. The single
      phosphorylated residues were systematically mutated and the resulting strains and
      Pol I preparations were analyzed in cellular growth, Pol I composition, stability
      and genetic interaction with non-essential components of the transcription
      machinery. Surprisingly, all Pol I phosphorylations analyzed were found to be non
      essential post-translational modifications. However, one mutation (subunit A190
      S685D) led to higher growth rates in the presence of 6AU or under environmental
      stress conditions, and was synthetically lethal with a deletion of the Pol I
      subunit A12.2, suggesting a role in RNA cleavage/elongation or termination. Our
      results suggest that individual major or constitutively phosphorylated residues
      contribute to non-essential Pol I-functions.

PMID- 18084033
TI  - Oxidation of single-stranded oligonucleotides by carbonate radical anions:
      generating intrastrand cross-links between guanine and thymine bases separated by
      cytosines.
AB  - The carbonate radical anion is a biologically important one-electron oxidant that
      can directly abstract an electron from guanine, the most easily oxidizable DNA
      base. Oxidation of the 5'-d(CCTACGCTACC) sequence by photochemically generated
      CO3*- radicals in low steady-state concentrations relevant to biological
      processes results in the formation of spiroiminodihydantoin diastereomers and a
      previously unknown lesion. The latter was excised from the oxidized
      oligonucleotides by enzymatic digestion with nuclease P1 and alkaline phosphatase
      and identified by LC-MS/MS as an unusual intrastrand cross-link between guanine
      and thymine. In order to further characterize the structure of this lesion, 5'
      d(GpCpT) was exposed to CO3*- radicals, and the cyclic nature of the 5'
      d(G*pCpT*) cross-link in which the guanine C8-atom is bound to the thymine N3
      atom was confirmed by LC-MS/MS, 1D and 2D NMR studies. The effect of bridging C
      bases on the cross-link formation was studied in the series of 5'-d(GpC(n)pT) and
      5'-d(TpC(n)pG) sequences with n = 0, 1, 2 and 3. Formation of the G*-T* cross
      links is most efficient in the case of 5'-d(GpCpT). Cross-link formation (n = 0)
      was also observed in double-stranded DNA molecules derived from the self
      complementary 5'-d(TTACGTACGTAA) sequence following exposure to CO3*- radicals
      and enzymatic excision of the 5'-d(G*pT*) product.

PMID- 18084034
TI  - ERK is a novel regulatory kinase for poly(A) polymerase.
AB  - Poly(A) polymerase (PAP), which adds poly(A) tails to the 3' end of mRNA, can be
      phosphorylated at several sites in the C-terminal domain. Phosphorylation often
      mediates regulation by extracellular stimuli, suggesting PAP may be regulated by
      such stimuli. In this study, we found that phosphorylation of PAP was increased
      upon growth stimulation and that the mitogen-activated protein kinase ERK was
      responsible for the increase in phosphorylation. We identified serine 537 of PAP
      as a unique phosphorylation site by ERK. PAP phosphorylation of serine 537 by ERK
      increased its nonspecific polyadenylation activity in vitro. This PAP activity
      was also activated by stimulation of ERK with phorbol-12-myristate-13-acetate in
      vivo. These data suggest that ERK is a novel regulatory kinase for PAP and
      further, that PAP activity could be regulated by extracellular stimuli through an
      ERK-dependent signaling pathway(s).

PMID- 18084035
TI  - Studies on the mechanism of inhibition of bacterial ribonuclease P by
      aminoglycoside derivatives.
AB  - Ribonuclease P (RNase P) is a Mg2+-dependent endoribonuclease responsible for the
      5'-maturation of transfer RNAs. It is a ribonucleoprotein complex containing an
      essential RNA and a varying number of protein subunits depending on the source:
      at least one, four and nine in Bacteria, Archaea and Eukarya, respectively. Since
      bacterial RNase P is required for viability and differs in structure/subunit
      composition from its eukaryal counterpart, it is a potential antibacterial
      target. To elucidate the basis for our previous finding that the hexa-arginine
      derivative of neomycin B is 500-fold more potent than neomycin B in inhibiting
      bacterial RNase P, we synthesized hexa-guanidinium and -lysyl conjugates of
      neomycin B and compared their inhibitory potential. Our studies indicate that
      side-chain length, flexibility and composition cumulatively account for the
      inhibitory potency of the aminoglycoside-arginine conjugates (AACs). We also
      demonstrate that AACs interfere with RNase P function by displacing Mg2+ ions.
      Moreover, our finding that an AAC can discriminate between a bacterial and
      archaeal (an experimental surrogate for eukaryal) RNase P holoenzyme lends
      promise to the design of aminoglycoside conjugates as selective inhibitors of
      bacterial RNase P, especially once the structural differences in RNase P from the
      three domains of life have been established.

PMID- 18084037
TI  - No elevation of blood urea level in a dehydrated patient with central diabetes
      insipidus.

PMID- 18084036
TI  - Recombineering with tolC as a selectable/counter-selectable marker: remodeling
      the rRNA operons of Escherichia coli.
AB  - This work describes the novel use of tolC as a selectable/counter-selectable
      marker for the facile modification of DNA in Escherichia coli. Expression of TolC
      (an outer membrane protein) confers relative resistance to toxic small molecules,
      while its absence renders the cell tolerant to colicin E1. These features,
      coupled with the lambdaredgam recombination system, allow for selection of tolC
      insertions/deletions anywhere on the E. coli chromosome or on plasmid DNA. This
      methodology obviates the need for minimal growth media, specialized wash
      protocols and the lengthy incubation times required by other published
      recombineering methods. As a rigorous test of the TolC selection system, six out
      of seven 23S rRNA genes were consecutively and seamlessly removed from the E.
      coli chromosome without affecting expression of neighboring genes within the
      complex rrn operons. The resulting plasmid-free strain retains one 23S rRNA gene
      (rrlC) in its natural location on the chromosome and is the first mutant of its
      kind. These new rRNA mutants will be useful in the study of rRNA gene regulation
      and ribosome function. Given its high efficiency, low background and facility in
      rich media, tolC selection is a broadly applicable method for the modification of
      DNA by recombineering.

PMID- 18084038
TI  - Sleep disruptions in parents of children and adolescents with chronic illnesses:
      prevalence, causes, and consequences.
AB  - OBJECTIVE: Provide a comprehensive review of the existing literature on the
      prevalence, causes, and consequences of sleep disruptions in parents of youth
      with chronic illnesses. METHODS: A comprehensive literature search of PsychInfo,
      MEDLINE, and CINAHL for articles related to sleep in parents of youth with
      chronic illnesses yielded 59 potential articles, with 19 meeting inclusion
      criteria. RESULTS: Parents of children with eczema were the most commonly studied
      group. The prevalence of sleep disruptions was 15-86%. Potential causes of parent
      sleep disruptions included nighttime caregiving, monitoring of the child's
      illness, and stress related to the child's illness. Consequences included poor
      sleep quality, depression, and anxiety. CONCLUSIONS: Parents of youth with
      chronic illnesses experience sleep disruptions, providing a potential mechanism
      to explain elevated rates of negative daytime functioning found in previous
      studies. To provide interventions and support for these parents, additional
      research is needed to address the limitations of the existing literature.

PMID- 18084039
TI  - Deletion of CFHR3 and CFHR1 genes in age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) impairs vision for approximately 7.5
      million Americans. Both susceptibility variants and protective haplotypes in the
      complement factor H (CFH) gene modulate risk for AMD. Recently, deletion of the
      'CFH-related' genes CFHR1 and CFHR3 was found to be segregating with a particular
      CFH haplotype, which reduced the risk of AMD. We tested the deletion for
      association in a Caucasian population of 780 cases and 265 controls and examined
      its effect in the context of known AMD risk factors. The deletion did not
      segregate perfectly with any one SNP, as previously suggested. CFH haplotype P2
      was the most frequent haplotype in deletion homozygotes (47%), and the majority
      (14/16) of these individuals were homozygous for the non-risk allele of Y402H.
      Overall, deletion homozygosity was significantly more frequent in controls than
      cases (2.6% controls, 0.8% cases, P = 0.025, OR = 0.29, 95% CI = 0.10-0.86).
      After controlling for age, Y402H, smoking and LOC387715 A69S, the protective
      effect of the deletion was no longer statistically significant (P = 0.27).
      However, using a CFH haplotype that all deletion homozygotes share as a surrogate
      for the deletion, this marker remained modestly associated with AMD after
      adjustment for known risk factors (OR = 0.63, 95% CI 0.39-1.04, P = 0.07).
      Therefore, deletion of CFHR1 and CFHR3 may account for a small portion of the
      protection from AMD associated with particular haplotypes in CFH. The presence of
      protective haplotypes in CFH that do not carry the deletion, suggests that other
      protective variants in this region have yet to be discovered.

PMID- 18084040
TI  - Advance directives and the rocky waters of anticipatory decision-making.

PMID- 18084041
TI  - Nuclear localization signal and phosphorylation of Serine350 specify
      intracellular localization of DRAK2.
AB  - DAP kinase-related apoptosis-inducing kinase 2 (DRAK2) is a serine/threonine
      kinase of the death-associated protein kinase family. DRAK2 mediates apoptosis
      induced by extracellular stimuli, including UV irradiation and interleukin-2, and
      also regulates T-cell receptor sensitivity in developing thymocytes. During these
      events, the subcellular localization of DRAK2 changes between the nucleus and
      cytoplasm. We found that DRAK2 has a putative nuclear-localization signal (NLS)
      sequence. Mutations in this sequence interfered with DRAK2 localization to the
      nucleus. Furthermore, green fluorescence protein fused to the putative NLS
      accumulated in the nucleus, indicating that the putative sequence functions as an
      NLS. We also found that the function of the NLS was regulated by phosphorylation.
      Phorbol myristate acetate (PMA) induced the accumulation of DRAK2 in the
      cytoplasm of NIH3T3 cells, whereas in the absence of PMA, DRAK2 was localized to
      the nucleus. Ectopic expression of PKC-gamma induced cytoplasmic localization of
      DRAK2 and PKC-gamma phosphorylated Ser350 flanking the NLS. DRAK2, but not the
      Ser350Asp mutant, accumulated in the nuclei of ACL-15 cells in response to UV
      irradiation. These results suggest that phosphorylation of Ser350 plays an
      essential role in regulating translocation of DRAK2 to the nucleus from the
      cytoplasm, possibly by affecting the activity of the NLS.

PMID- 18084042
TI  - Interdomain interaction of cyclic AMP receptor protein in the absence of cyclic
      AMP.
AB  - Interdomain interaction of apo-cyclic AMP receptor protein (apo-CRP) was
      qualified using its isolated domains. The cAMP-binding domain was prepared by a
      limited proteolysis, while the DNA-binding domain was constructed as a
      recombinant protein. Three different regions making interdomain contacts in apo
      CRP were identified by a sequence-specific comparison of the HSQC spectra. The
      results indicated that apo-CRP possesses characteristic modules of interdomain
      interaction that are properly organized to suppress activity and to sense and
      transfer the cAMP binding signals. Particularly, the inertness of the DNA-binding
      motif in apo-CRP was attributable to the participation of F-helices in the
      interdomain contacts.

PMID- 18084043
TI  - Staphylococcus aureus MurC participates in L-alanine recognition via histidine
      343, a conserved motif in the shallow hydrophobic pocket.
AB  - UDP-N-acetylmuramic acid:L-alanine ligase that is encoded by the murC gene, is
      indispensable for bacterial peptidoglycan biosynthesis and an important target
      for the development of antibacterial agents. Structure of MurC ligase with
      substrates has been described, however, little validation via studying the
      effects of mutations on the structure of MurC has been performed. In this study,
      we carried out a functional in vitro and in vivo characterization of
      Staphylococcus aureus MurCH343Y protein that has a temperature-sensitive mutation
      of a conserved residue in the predicted shallow hydrophobic pocket that holds a
      short L-alanine side chain. Purified H343Y and wild-type MurC had K(m) values for
      L-alanine of 3.2 and 0.44 mM, respectively, whereas there was no significant
      difference in their K(m) values for ATP and UDP-N-acetylmuramic acid, suggesting
      the specific alteration of L-alanine recognition in MurCH343Y protein. In a
      synthetic medium that excluded L-alanine, S. aureus murCH343Y mutant cells showed
      an allele-specific slow growth phenotype that was suppressed by addition of L
      alanine. These results suggest that His343 of S. aureus MurC is essential for
      high-affinity binding to L-alanine both in vitro and in vivo and provide
      experimental evidence supporting the structural information of MurC ligase.

PMID- 18084044
TI  - A gene-shuffled glyphosate acetyltransferase protein from Bacillus licheniformis
      (GAT4601) shows no evidence of allergenicity or toxicity.
AB  - The glyphosate acetyltransferase (gat) gene from Bacillus licheniformis was
      subjected to multiple rounds of gene shuffling to optimize kinetics of
      corresponding GAT proteins to acetylate the herbicide active ingredient
      glyphosate. Genetically modified soybeans expressing the gat4601 gene (356043
      soybeans) are tolerant to the application of glyphosate. The current manuscript
      reports the outcome of the allergenicity and toxicity assessment for the GAT4601
      protein. Bioinformatic comparison of the amino acid sequence of GAT4601 did not
      identify similarities to known allergenic or toxic proteins. In vitro studies
      conducted with heterologously produced GAT4601 protein demonstrated that it was
      rapidly degraded in simulated gastric fluid containing pepsin (< 30 s) and in
      simulated intestinal fluid containing pancreatin (< 2 min) and completely
      inactivated at temperatures above 56 degrees C. The GAT4601 protein expressed in
      planta is not glycosylated and similar protein profiles were observed in flour
      extracts from 356043 soybeans and nontransgenic near isoline comparator soybeans
      (Jack) using serum from soy allergic persons. No evidence of adverse effects was
      observed in mice following acute oral exposure to 2000 mg/kg of GAT4601 protein
      or in a repeated dose dietary exposure study at doses of 800-1000 mg/kg/day. This
      comprehensive assessment demonstrates that the GAT4601 protein does not present a
      risk for adverse effects in humans when used in the context of agricultural
      biotechnology.

PMID- 18084045
TI  - Gene expression profiles in rainbow trout, Onchorynchus mykiss, exposed to a
      simple chemical mixture.
AB  - Among proposed uses for microarrays in environmental toxiciology is the
      identification of key contributors to toxicity within a mixture. However, it
      remains uncertain whether the transcriptomic profiles resulting from exposure to
      a mixture have patterns of altered gene expression that contain identifiable
      contributions from each toxicant component. We exposed isogenic rainbow trout
      Onchorynchus mykiss, to sublethal levels of ethynylestradiol, 2,2,4,4
      tetrabromodiphenyl ether, and chromium VI or to a mixture of all three toxicants
      Fluorescently labeled complementary DNA (cDNA) were generated and hybridized
      against a commercially available Salmonid array spotted with 16,000 cDNAs. Data
      were analyzed using analysis of variance (p<0.05) with a Benjamani-Hochberg
      multiple test correction (Genespring [Agilent] software package) to identify up
      and downregulated genes. Gene clustering patterns that can be used as "expression
      signatures" were determined using hierarchical cluster analysis. The gene
      ontology terms associated with significantly altered genes were also used to
      identify functional groups that were associated with toxicant exposure. Cross
      ontological analytics approach was used to assign functional annotations to genes
      with "unknown" function. Our analysis indicates that transcriptomic profiles
      resulting from the mixture exposure resemble those of the individual contaminant
      exposures, but are not a simple additive list. However, patterns of altered genes
      representative of each component of the mixture are clearly discernible, and the
      functional classes of genes altered represent the individual components of the
      mixture. These findings indicate that the use of microarrays to identify
      transcriptomic profiles may aid in the identification of key stressors within a
      chemical mixture, ultimately improving environmental assessment.

PMID- 18084046
TI  - Carbon beam therapy in recurrent ovarian cancer.

PMID- 18084047
TI  - Trastuzumab in pregnancy associated with poor fetal outcome.

PMID- 18084048
TI  - Effects of recombinant LH treatment on folliculogenesis and responsiveness to FSH
      stimulation.
AB  - BACKGROUND: The role of LH in sensitizing antral follicles to FSH is unclear. LH
      is required for normal hormone production and normal oocyte and embryo
      development, but follicular responses to LH may depend upon the stage of
      development. Potential roles at the early follicular phase were explored in a
      clinical setting by employing a sequential approach to stimulation by recombinant
      human (r-h) LH followed by r-hFSH in women who were profoundly down-regulated by
      depo GnRH agonist. METHODS: We employed a multi-centre, prospective, randomized
      approach. Women (n = 146) were treated in a long course high-dose GnRH agonist
      (Decapeptyl, 4.2 mg s.c.) protocol and were randomized to receive r-hLH (Luveris,
      300 IU/day) for a fixed 7 days, or no r-hLH treatment. This was followed by a
      standard r-hFSH stimulation regime (Gonal-F, 150 IU/day). Ultrasound and hormone
      assessments of responses were measured at the start of r-hLH treatment, on FSH
      stimulation Days 0 and 8 and at the time of HCG administration. RESULTS: The LH
      treatment was associated with increased small antral follicles prior to FSH
      stimulation (P = 0.007), and an increased yield of normally fertilized (2 PN)
      embryos (P = 0.03). There was no influence of the r-hLH pretreatment upon hormone
      profiles or ultrasound assessments during the FSH phase. Anti-mullerian hormone
      increased in both groups during the week prior to FSH stimulation (P = 0.002).
      CONCLUSIONS: This sequential approach to the use of r-hLH in standard IVF showed
      a possible modest clinical benefit. The results support other recent work
      exploring up-regulated androgen drive upon follicular metabolism indicating that
      clinical benefit may be obtainable after further practical explorations of the
      concept.

PMID- 18084049
TI  - C-terminal tailoring of L-type calcium channel function.

PMID- 18084051
TI  - Three-dimensional structure/function analysis of SCP-2-like2 reveals differences
      among SCP-2 family members.
AB  - Mosquito sterol carrier protein-2 (AeSCP-2) and sterol carrier protein-2-like2
      (AeSCP-2L2) are members of the SCP-2 protein family with similar expression
      profiles in the mosquito life cycle. In an effort to understand how lipids can be
      transported by different SCP-2 proteins, the three-dimensional crystal structure
      of AeSCP-2L2 was solved at 1.7 A resolution. AeSCP-2L2 forms a dimer and binds
      three fatty acids, one of which resides in a position within the internal cavity
      at a right angle to the others. This first report of ligand-bound dimerized
      protein in the SCP-2 protein family indicates that the family has a much more
      divergent mode of interaction with ligands than previously reported. The
      potential function of AeSCP-2L2 was investigated via in vivo incorporation of
      [(3)H]cholesterol and [3H]palmitic acid. Overexpression of AeSCP-2L2 in mosquito
      cells leads to an increased uptake of free fatty acid, whereas knockdown of AeSCP
      2L2 in adult females decreases the accumulation of free fatty acid in the fat
      body from a blood meal. In contrast, overexpression or knockdown of AeSCP-2L2 has
      no effect on cholesterol uptake. Our results suggest that the main function of
      AeSCP-2L2 is as a general intracellular fatty acid carrier, as opposed to having
      a dedicated role in cholesterol transport.

PMID- 18084053
TI  - A theory of frequency domain invariants: spherical harmonic identities for
      BRDF/lighting transfer and image consistency.
AB  - This paper develops a theory of frequency domain invariants in computer vision.
      We derive novel identities using spherical harmonics, which are the angular
      frequency domain analog to common spatial domain invariants such as reflectance
      ratios. These invariants are derived from the spherical harmonic convolution
      framework for reflection from a curved surface. Our identities apply in a number
      of canonical cases, including single and multiple images of objects under the
      same and different lighting conditions. One important case we consider is two
      different glossy objects in two different lighting environments. For this case,
      we derive a novel identity, independent of the specific lighting configurations
      or BRDFs, that allows us to directly estimate the fourth image if the other three
      are available. The identity can also be used as an invariant to detecttampering
      in the images. While this paper is primarily theoretical, it has the potential to
      lay the mathematical foundations for two important practical applications. First,
      we can develop more general algorithms for inverse rendering problems, which can
      directly relight and change material properties by transferring the BRDF or
      lighting from another object or illumination. Second, we can check the
      consistency of an image, to detect tampering or image splicing.

PMID- 18084054
TI  - Three-view multibody structure from motion.
AB  - We propose a geometric approach to 3-D motion segmentation from point
      correspondences in three perspective views. We demonstrate that after applying a
      polynomial embedding to the point correspondences they become related by the
      socalled multibody trilinear constraint and its associated multibody trifocal
      tensor, which are natural generalizations of the trilinear constraint and the
      trifocal tensor to multiple motions. We derive a rank constraint on the embedded
      correspondences, from which one can estimate the number of independent motions as
      well as linearly solve for the multibody trifocal tensor. We then show how to
      compute the epipolar lines associated with each image point from the common root
      of a set of univariate polynomials and the epipoles by solving a pair of plane
      clustering problems using Generalized PCA (GPCA). The individual trifocal tensors
      are then obtained from the second order derivatives of the multibody trilinear
      constraint. Given epipolar lines and epipoles, or trifocal tensors, one can
      immediately obtain an initial clustering of the correspondences. We use this
      clustering to initialize an iterative algorithm that alternates between the
      computation of the trifocal tensors and the segmentation of the correspondences.
      We test our algorithm on various synthetic and real scenes, and compare with
      other algebraic and iterative algorithms.

PMID- 18084052
TI  - Heart disease management by women: does intervention format matter?
AB  - A randomized controlled trial of two formats of a program (Women Take PRIDE) to
      enhance management of heart disease by patients was conducted. Older women (N =
      575) were randomly assigned to a group or self-directed format or to a control
      group. Data regarding symptoms, functional health status, and weight were
      collected at baseline and at 4, 12, and 18 months. The formats produced different
      outcomes. At 18 months, the self-directed format was better than the control in
      reducing the number (p < or = .02), frequency (p < or = .03), and bothersomeness
      (p < or = .02) of cardiac symptoms. The self-directed format was also better than
      the group format in reducing symptom frequency of all types (p < or = .04). The
      group format improved ambulation at 12 months (p < or = .04) and weight loss at
      18 months (p < or = .03), and group participants were more likely to complete the
      program ( p < or = .05). The availability of different learning formats could
      enhance management of cardiovascular disease by patients.

PMID- 18084055
TI  - A closed-form solution to natural image matting.
AB  - Interactive digital matting, the process of extracting a foreground object from
      an image based on limited user input, is an important task in image and video
      editing. From a computer vision perspective, this task is extremely challenging
      because it is massively ill-posed -- at each pixel we must estimate the
      foreground and the background colors, as well as the foreground opacity ("alpha
      matte") from a single color measurement. Current approaches either restrict the
      estimation to a small part of the image, estimating foreground and background
      colors based on nearby pixels where they are known, or perform iterative
      nonlinear estimation by alternating foreground and background color estimation
      with alpha estimation. In this paper we present a closed-form solution to natural
      image matting. We derive a cost function from local smoothness assumptions on
      foreground and background colors, and show that in the resulting expression it is
      possible to analytically eliminate the foreground and background colors to obtain
      a quadratic cost function in alpha. This allows us to find the globally optimal
      alpha matte by solving a sparse linear system of equations. Furthermore, the
      closed-form formula allows us to predict the properties of the solution by
      analyzing the eigenvectors of a sparse matrix, closely related to matrices used
      in spectral image segmentation algorithms. We show that high quality mattes for
      natural images may be obtained from a small amount of user input.

PMID- 18084056
TI  - K-nearest neighbor finding using MaxNearestDist.
AB  - Similarity searching often reduces to finding the k nearest neighbors to a query
      object. Finding the k nearest neighbors is achieved by applying either a depth-
      first or a best-first algorithm to the search hierarchy containing the data.
      These algorithms are generally applicable to any index based on hierarchical
      clustering. The idea is that the data is partitioned into clusters which are
      aggregated to form other clusters, with the total aggregation being represented
      as a tree. These algorithms have traditionally used a lower bound corresponding
      to the minimum distance at which a nearest neighbor can be found (termed MinDist)
      to prune the search process by avoiding the processing of some of the clusters as
      well as individual objects when they can be shown to be farther from the query
      object q than all of the current k nearest neighbors of q. An alternative pruning
      technique that uses an upper bound corresponding to the maximum possible distance
      at which a nearest neighbor is guaranteed to be found (termed MaxNearestDist) is
      described. The MaxNearestDist upper bound is adapted to enable its use for
      finding the k nearest neighbors instead of just the nearest neighbor (i.e., k=1)
      as in its previous uses. Both the depth-first and best-first k-nearest neighbor
      algorithms are modified to use MaxNearestDist, which is shown to enhance both
      algorithms by overcoming their shortcomings. In particular, for the depth-first
      algorithm, the number of clusters in the search hierarchy that must be examined
      is not increased thereby potentially lowering its execution time, while for the
      best-first algorithm, the number of clusters in the search hierarchy that must be
      retained in the priority queue used to control the ordering of processing of the
      clusters is also not increased, thereby potentially lowering its storage
      requirements.

PMID- 18084057
TI  - Weighted pseudometric discriminatory power improvement using a Bayesian logistic
      regression model based on a variational method.
AB  - In this paper, we investigate the effectiveness of a Bayesian logistic regression
      model to compute the weights of a pseudo-metric, in order to improve its
      discriminatory capacity and thereby increase image retrieval accuracy. In the
      proposed Bayesian model, the prior knowledge of the observations is incorporated
      and the posterior distribution is approximated by a tractable Gaussian form using
      variational transformation and Jensen's inequality, which allow a fast and
      straightforward computation of the weights. The pseudo-metric makes use of the
      compressed and quantized versions of wavelet decomposed feature vectors, and in
      our previous work, the weights were adjusted by classical logistic regression
      model. A comparative evaluation of the Bayesian and classical logistic regression
      models is performed for content-based image retrieval as well as for other
      classification tasks, in a decontextualized evaluation framework. In this same
      framework, we compare the Bayesian logistic regression model to some relevant
      state-of-the-art classification algorithms. Experimental results show that the
      Bayesian logistic regression model outperforms these linear classification
      algorithms, and is a significantly better tool than the classical logistic
      regression model to compute the pseudo-metric weights and improve retrieval and
      classification performance. Finally, we perform a comparison with results
      obtained by other retrieval methods.

PMID- 18084058
TI  - Multicamera people tracking with a probabilistic occupancy map.
AB  - Given two to four synchronized video streams taken at eye level and from
      different angles, we show that we can effectively combine a generative model with
      dynamic programming to accurately follow up to six individuals across thousands
      of frames in spite of significant occlusions and lighting changes. In addition,
      we also derive metrically accurate trajectories for each one of them. Our
      contribution is twofold. First, we demonstrate that our generative model can
      effectively handle occlusions in each time frame independently, even when the
      only data available comes from the output of a simple background subtraction
      algorithm and when the number of individuals is unknown a priori. Second, we show
      that multi-person tracking can be reliably achieved by processing individual
      trajectories separately over long sequences, provided that a reasonable heuristic
      is used to rank these individuals and avoid confusing them with one another.

PMID- 18084059
TI  - Gaussian process dynamical models for human motion.
AB  - We introduce Gaussian process dynamical models (GPDM) for nonlinear time series
      analysis, with applications to learning models of human pose and motion from high
      dimensionalmotion capture data. A GPDM is a latent variable model. It comprises a
      low-dimensional latent space with associated dynamics, and a map from the latent
      space to an observation space. We marginalize out the model parameters in closed
      form, using Gaussian process priors for both the dynamics and the observation
      mappings. This results in a non-parametric model for dynamical systems that
      accounts for uncertainty in the model. We demonstrate the approach, and compare
      four learning algorithms on human motion capture data in which each pose is 50
      dimensional. Despite the use of small data sets, the GPDM learns an effective
      representation of the nonlinear dynamics in these spaces.

PMID- 18084060
TI  - Automatic estimation and removal of noise from a single image.
AB  - Image denoising algorithms often assume an additive white Gaussian noise (AWGN)
      process that is independent of the actual RGB values. Such approaches are not
      fully automatic and cannot effectively remove color noise produced by todays CCD
      digital camera. In this paper, we propose a unified framework for two tasks:
      automatic estimation and removal of color noise from a single image using
      piecewise smooth image models. We introduce the noise level function (NLF), which
      is a continuous function describing the noise level as a function of image
      brightness. We then estimate an upper bound of the real noise level function by
      fitting a lower envelope to the standard deviations of per-segment image
      variances. For denoising, the chrominance of color noise is significantly removed
      by projecting pixel values onto a line fit to the RGB values in each segment.
      Then, a Gaussian conditional random field (GCRF) is constructed to obtain the
      underlying clean image from the noisy input. Extensive experiments are conducted
      to test the proposed algorithm, which is shown to outperform state-of-the-art
      denoising algorithms.

PMID- 18084061
TI  - Plane-based optimization for 3D object reconstruction from single line drawings.
AB  - In previous optimization-based methods of 3D planar-faced object reconstruction
      from single 2D line drawings, the missing depths of the vertices of a line
      drawing (and other parameters in some methods) are used as the variables of the
      objective functions. A 3D object with planar faces is derived by finding values
      for these variables that minimize the objective functions. These methods work
      well for simple objects with a small number N of variables. As N grows, however,
      it is very difficult for them to find expected objects. This is because with the
      nonlinear objective functions in a space of large dimension N, the search for
      optimal solutions can easily get trapped into local minima. In this paper, we use
      the parameters of the planes that pass through the planar faces of an object as
      the variables of the objective function. This leads to a set of linear
      constraints on the planes of the object, resulting in a much lower dimensional
      nullspace where optimization is easier to achieve. We prove that the dimension of
      this nullspace is exactly equal to the minimum number of vertex depths which
      define the 3D object. Since a practical line drawing is usually not an exact
      projection of a 3D object, we expand the nullspace to a larger space based on the
      singular value decomposition of the projection matrix of the line drawing. In
      this space, robust 3D reconstruction can be achieved. Compared with two most
      related methods, our method not only can reconstruct more complex 3D objects from
      2D line drawings, but also is computationally more efficient.

PMID- 18084062
TI  - Stereo processing by semiglobal matching and mutual information.
AB  - This paper describes the Semi-Global Matching (SGM) stereo method. It uses a
      pixelwise, Mutual Information based matching cost for compensating radiometric
      differences of input images. Pixelwise matching is supported by a smoothness
      constraint that is usually expressed as a global cost function. SGM performs a
      fast approximation by pathwise optimizations from all directions. The discussion
      also addresses occlusion detection, subpixel refinement and multi-baseline
      matching. Additionally, postprocessing steps for removing outliers, recovering
      from specific problems of structured environments and the interpolation of gaps
      are presented. Finally, strategies for processing almost arbitrarily large images
      and fusion of disparity images using orthographic projection are proposed.A
      comparison on standard stereo images shows that SGM is among the currently top
      ranked algorithms and is best, if subpixel accuracy is considered. The complexity
      is linear to the number of pixels and disparity range, which results in a runtime
      of just 1-2s on typical test images. An in depth evaluation of the Mutual
      Information based matching cost demonstrates a tolerance against a wide range of
      radiometric transformations. Finally, examples of reconstructions from huge
      aerial frame and pushbroom images demonstrate that the presented ideas are
      working well on practical problems.

PMID- 18084063
TI  - Likelihood ratio-based biometric score fusion.
AB  - Multibiometric systems fuse information from different sources to compensate for
      the limitations in performance of individual matchers. We propose a framework for
      optimal combination of match scores that is based on the likelihood ratio test.
      The distributions of genuine and impostor match scores are modeled as finite
      Gaussian mixture model. The proposed fusion approach is general in its ability to
      handle (i) discrete values in biometric match score distributions, (ii) arbitrary
      scales and distributions of match scores, (iii) correlation between the scores of
      multiple matchers and (iv) sample quality of multiple biometric sources.
      Experiments on three multibiometric databases indicate that the proposed fusion
      framework achieves consistently high performance compared to commonly used score
      fusion techniques based on score transformation and classification.

PMID- 18084064
TI  - MultiK-MHKS: a novel multiple kernel learning algorithm.
AB  - In this paper, we develop a new effective multiple kernel learning algorithm.
      First, map the input data into m different feature spaces by m empirical kernels,
      where each generatedfeature space is takenas one viewof the input space. Then
      through the borrowing the motivating argument from Canonical Correlation Analysis
      (CCA)that can maximally correlate the m views in the transformed coordinates, we
      introduce a special term called Inter-Function Similarity Loss R IFSL into the
      existing regularization framework so as to guarantee the agreement of multi-view
      outputs. In implementation, we select the Modification of Ho-Kashyap algorithm
      with Squared approximation of the misclassification errors (MHKS) as the
      incorporated paradigm, and the experimental results on benchmark data sets
      demonstrate the feasibility and effectiveness of the proposed algorithm named
      MultiK-MHKS.

PMID- 18084065
TI  - Bayesian-competitive consistent labeling for people surveillance.
AB  - This paper presents a novel and robust approach to consistent labeling for people
      surveillance in multi-camera systems. A general framework scalable to any number
      of cameras with overlapped views is devised. An off-line training process
      automatically computes ground-plane homography and recovers epipolar geometry.
      When a new object is detected in any one camera, hypotheses for potential
      matching objects in the other cameras are established. Each of the hypotheses is
      evaluated using a prior and likelihood value. The prior accounts for the
      positions of the potential matching objects, while the likelihood is computed by
      warping the vertical axis of the new object on the field of view of the other
      cameras and measuring the amount of match. In the likelihood, two contributions
      (forward and backward) are considered so as to correctly handle the case of
      groups of people merged into single objects. Eventually, a maximum-a-posteriori
      approach estimates the best label assignment for the new object. Comparisons with
      other methods based on homography and extensive outdoor experiments demonstrate
      that the proposed approach is accurate and robust in coping with segmentation
      errors and in disambiguating groups.

PMID- 18084066
TI  - Trajectory association across multiple airborne cameras.
AB  - A camera mounted on an aerial vehicle provides an excellent means for monitoring
      large areas of a scene. Utilizing several such cameras on different aerial
      vehicles allows further flexibility, in terms of increased visual scope and in
      the pursuit of multiple targets. In this paper, we address the problem of
      associating objects across multiple airborne cameras. Since the cameras are
      moving and often widely separated, direct appearance-based or proximity-based
      constraints cannot be used. Instead, we exploit geometric constraints on the
      relationship between the motion of each object across cameras, to test multiple
      association hypotheses, without assuming any prior calibration information. Given
      our scene model, we propose a likelihood function for evaluating a hypothesized
      association between observations in multiple cameras that is geometrically
      motivated. Since multiple cameras exist, ensuring coherency in association is an
      essential requirement, e.g. that transitive closure is maintained between more
      than two cameras. To ensure such coherency we pose the problem of maximizing the
      likelihood function as a k-dimensional matching and use an approximation to find
      the optimal assignment of association. Using the proposed error function,
      canonical trajectories of each object and optimal estimates of inter-camera
      transformations (in a maximum likelihood sense) are computed. Finally, we show
      that as a result of associating objects across the cameras, a concurrent
      visualization of multiple aerial video streams is possible and that, under
      special conditions, trajectories interrupted due to occlusion or missing
      detections can be repaired. Results are shown on a number of real and controlled
      scenarios with multiple objects observed by multiple cameras, validating our
      qualitative models, and through simulation quantitative performance is also
      reported.

PMID- 18084067
TI  - Structures of human deoxycytidine kinase product complexes.
AB  - Human deoxycytidine kinase (dCK) is involved in the nucleotide-biosynthesis
      salvage pathway and has also been shown to phosphorylate several antitumor and
      antiviral prodrugs. The structures of dCK alone and the dead-end complex of dCK
      with substrate nucleoside and product ADP or UDP have previously been reported;
      however, there is currently no structure available for a substrate or product
      complex. Here, the structures of dCK complexes with the products dCMP, UDP and
      Mg2+ ion, and with dAMP, UDP and Mg2+ ion are reported. Structural comparisons
      show that the product complexes with UDP and a dead-end complex with substrate
      and UDP have similar active-site conformations.

PMID- 18084068
TI  - Structure-assisted discovery of an aminothiazole derivative as a lead molecule
      for inhibition of bacterial fatty-acid synthesis.
AB  - Fatty-acid synthesis in bacteria is of great interest as a target for the
      discovery of antibacterial compounds. The addition of a new acetyl moiety to the
      growing fatty-acid chain, an essential step in this process, is catalyzed by beta
      ketoacyl-ACP synthase (KAS). It is inhibited by natural antibiotics such as
      cerulenin and thiolactomycin; however, these lack the requirements for optimal
      drug development. Structure-based biophysical screening revealed a novel
      synthetic small molecule, 2-phenylamino-4-methyl-5-acetylthiazole, that binds to
      Escherichia coli KAS I with a binding constant of 25 microM as determined by
      fluorescence titration. A 1.35 A crystal structure of its complex with its target
      reveals noncovalent interactions with the active-site Cys163 and hydrophobic
      residues of the fatty-acid binding pocket. The active site is accessible through
      an open conformation of the Phe392 side chain and no conformational changes are
      induced at the active site upon ligand binding. This represents a novel binding
      mode that differs from thiolactomycin or cerulenin interaction. The structural
      information on the protein-ligand interaction offers strategies for further
      optimization of this low-molecular-weight compound.

PMID- 18084069
TI  - Structure of the branched-chain keto acid decarboxylase (KdcA) from Lactococcus
      lactis provides insights into the structural basis for the chemoselective and
      enantioselective carboligation reaction.
AB  - The thiamin diphosphate (ThDP) dependent branched-chain keto acid decarboxylase
      (KdcA) from Lactococcus lactis catalyzes the decarboxylation of 3-methyl-2
      oxobutanoic acid to 3-methylpropanal (isobutyraldehyde) and CO2. The enzyme is
      also able to catalyze carboligation reactions with an exceptionally broad
      substrate range, a feature that makes KdcA a potentially valuable biocatalyst for
      C-C bond formation, in particular for the enzymatic synthesis of diversely
      substituted 2-hydroxyketones with high enantioselectivity. The crystal structures
      of recombinant holo-KdcA and of a complex with an inhibitory ThDP analogue
      mimicking a reaction intermediate have been determined to resolutions of 1.6 and
      1.8 A, respectively. KdcA shows the fold and cofactor-protein interactions
      typical of thiamin-dependent enzymes. In contrast to the tetrameric assembly
      displayed by most other ThDP-dependent decarboxylases of known structure, KdcA is
      a homodimer. The crystal structures provide insights into the structural basis of
      substrate selectivity and stereoselectivity of the enzyme and thus are suitable
      as a framework for the redesign of the substrate profile in carboligation
      reactions.

PMID- 18084070
TI  - Structure of the human Tim44 C-terminal domain in complex with pentaethylene
      glycol: ligand-bound form.
AB  - Familial oncocytic thyroid carcinoma is associated with a missense mutation,
      P308Q, in the C-terminal domain of Tim44. Tim44 is the mitochondrial inner
      membrane translocase subunit and it functions as a membrane anchor for the
      mitochondrial heat-shock protein 70 (mtHsp70). Here, the crystal structure of the
      human Tim44 C-terminal domain complexed with pentaethylene glycol has been
      determined at 1.9 A resolution. The overall structure resembles that of the
      nuclear transport factor 2-like domain. In the crystal structure, pentaethylene
      glycol molecules are associated at two potential membrane-binding sites: the
      large hydrophobic cavity and the highly conserved loop between the alpha1 and
      alpha2 helices near Pro308. A comparison with the yeast homolog revealed that
      lipid binding induces conformational changes around the alpha1-alpha2 loop,
      leading to slippage of the alpha1 helix along the large beta-sheet. These changes
      may play important roles in the translocation of polypeptides across the
      mitochondrial inner membrane.

PMID- 18084071
TI  - On the interrelationship between atomic displacement parameters (ADPs) and
      coordinates in protein structures.
AB  - Macromolecular models refined against X-ray diffraction data are typically
      described by a set of atomic coordinates and atomic displacement parameters
      (ADPs). Although it is intuitively obvious that the two cannot be independent of
      each other and although over time many attempts have been made to relate them to
      each other, such approaches have so far not been utilized in macromolecular
      structure refinement. It is demonstrated here that up to 50% of the total ADP
      variation in macromolecular structures may be successfully predicted solely based
      on the atomic coordinates and just three additional parameters per structure.
      This finding may have serious implications in macromolecular structure
      refinement, particularly at low resolution, as well as in structure validation.

PMID- 18084072
TI  - Comparison of two T-state structures of regulatory-chain mutants of Escherichia
      coli aspartate transcarbamoylase suggests that His20 and Asp19 modulate the
      response to heterotropic effectors.
AB  - Asp19 and His20 of Escherichia coli aspartate transcarbamoylase (EC 2.1.3.2)
      function in the binding of the triphosphate and ribose moieties of ATP and CTP
      and thereby may mediate important heterotropic regulation. The roles of these
      residues were investigated by individually mutating each of them to alanine and
      determining both the kinetic parameters and the structures of the mutant enzymes.
      The structures were determined by X-ray crystallography at 2.15 and 2.75 A
      resolution for His20Ar and Asp19Ar, respectively. Analysis was carried out on the
      unliganded T-state form. The structures of the mutants did not show gross
      structural divergence from the canonical T-state, but showed small and systematic
      differences that were analyzed by global conformational analysis. Structural
      analysis and comparison with other regulatory-chain mutants confirmed that the
      Asp19Ar mutant represents the stabilized T-state, while structural analysis of
      the His20Ar form indicated that it represents an equilibrium shifted towards the
      R-state. Global analysis of the Asp19Ar and His20Ar enzymes suggested a possible
      role as molecular modulators of the heterotropic effects caused by the binding of
      nucleotides at the regulatory site. These studies highlighted the structural
      determinants of T- or R-state stabilization. Additionally, application of the
      ;consensus modeling' methodology combined with high-resolution data allowed the
      determination of unclear structural features contributing to nucleotide
      specificity and the role of the N-termini of the regulatory chains.

PMID- 18084073
TI  - Triclinic lysozyme at 0.65 A resolution.
AB  - The crystal structure of triclinic hen egg-white lysozyme (HEWL) has been refined
      against diffraction data extending to 0.65 A resolution measured at 100 K using
      synchrotron radiation. Refinement with anisotropic displacement parameters and
      with the removal of stereochemical restraints for the well ordered parts of the
      structure converged with a conventional R factor of 8.39% and an R(free) of
      9.52%. The use of full-matrix refinement provided an estimate of the variances in
      the derived parameters. In addition to the 129-residue protein, a total of 170
      water molecules, nine nitrate ions, one acetate ion and three ethylene glycol
      molecules were located in the electron-density map. Eight sections of the main
      chain and many side chains were modeled with alternate conformations. The
      occupancies of the water sites were refined and this step is meaningful when
      assessed by use of the free R factor. A detailed description and comparison of
      the structure are made with reference to the previously reported triclinic HEWL
      structures refined at 0.925 A (at the low temperature of 120 K) and at 0.95 A
      resolution (at room temperature).

PMID- 18084074
TI  - Structure of the Bacillus subtilis OhrB hydroperoxide-resistance protein in a
      fully oxidized state.
AB  - The crystal structure of the fully oxidized form of the Bacillus subtilis organic
      hydroperoxide-resistance (OhrB) protein is reported at 2.1 A resolution. The
      electron density reveals an intact catalytic disulfide bond (Cys55-Cys119) in
      each of the two molecules, which are intertwined into a canonical obligate dimer.
      However, the stereochemistry of the disulfides is unorthodox and strained,
      suggesting that they are sensitive to reducing agents. A deep solvent-accessible
      gorge reaching Cys55 may represent the access route for the reductant.

PMID- 18084075
TI  - Experimental determination of optimal root-mean-square deviations of
      macromolecular bond lengths and angles from their restrained ideal values.
AB  - A number of inconsistencies are apparent in the recent research paper by
      Jaskolski et al. [(2007), Acta Cryst. D63, 611-620] concerning their
      recommendations for the values of the magnitude and resolution-dependence of the
      root-mean-square deviations (RMSDs) of bond lengths and angles from their
      restrained ideal values in macromolecular refinement, as well as their
      suggestions for the use of variable standard uncertainties dependent on atomic
      displacement parameters (ADPs) and occupancies. Whilst many of the comments and
      suggestions in the paper regarding updates for the ideal geometry values proposed
      by Engh and Huber are entirely reasonable and supported by the experimental
      evidence, the recommendations concerning the optimal values of RMSDs appear to be
      in conflict with previous experimental and theoretical work in this area [Tickle
      et al. (1998), Acta Cryst. D54, 243-252] and indeed appear to be based on a
      misunderstanding of the distinction between RMSD and standard uncertainty (SU).
      In contrast, it is proposed here that the optimal values of all desired weighting
      parameters, in particular the weighting parameters for the ADP differences and
      for the diffraction terms, be estimated by the purely objective procedure of
      maximizing the experiment-based log(free likelihood). In principle, this allows
      all weighting parameters that are not known accurately a priori to be scaled
      globally, relative to those that are known accurately, for an optimal refinement.
      The RMS Z score (RMSZ) is recommended as a more satisfactory statistic than the
      RMSD to assess the extent to which the geometry deviates from the ideal values
      and a theoretical rationale for the results obtained is presented in which the
      optimal RMSZ is identified as the calculated versus true Z-score correlation
      coefficient, the latter being a monotonic function of the resolution cutoff of
      the data. Regarding the proposal to use variable standard uncertainties, it is
      suggested that any departure from the current practice of using fixed weights for
      geometric restraints based on experimental values of standard uncertainties be
      subject to the same experiment-based validation.

PMID- 18084076
TI  - Numerology versus reality: a voice in a recent dispute.

PMID- 18084077
TI  - Structure of the minimized alpha/beta-hydrolase fold protein from Thermus
      thermophilus HB8.
AB  - The gene encoding TTHA1544 is a singleton found in the Thermus thermophilus HB8
      genome and encodes a 131-amino-acid protein. The crystal structure of TTHA1544
      has been determined at 2.0 A resolution by the single-wavelength anomalous
      dispersion method in order to elucidate its function. There are two molecules in
      the asymmetric unit. Each molecule consists of four alpha-helices and six beta
      strands, with the beta-strands composing a central beta-sheet. A structural
      homology search revealed that the overall structure of TTHA1544 resembles the
      alpha/beta-hydrolase fold, although TTHA1544 lacks the catalytic residues of a
      hydrolase. These results suggest that TTHA1544 represents the minimized
      alpha/beta-hydrolase fold and that an additional component would be required for
      its activity.

PMID- 18084078
TI  - The structure of allophycocyanin from Thermosynechococcus elongatus at 3.5 A
      resolution.
AB  - Cyanobacteria and red algae use light-harvesting pigments bound by proteins to
      capture solar radiation and to channel excitation energy into their reaction
      centres. In most cyanobacteria, a multi-megadalton soluble structure known as the
      phycobilisome is a major light-harvesting system. Allophycocyanin is the main
      component of the phycobilisome core, forming a link between the rest of the
      phycobilisome and the reaction-centre core. The crystal structure of
      allophycocyanin from Thermosynechococcus elongatus (TeAPC) has been determined
      and refined at 3.5 A resolution to a crystallographic R value of 26.0% (R(free) =
      28.5%). The structure was solved by molecular replacement using the
      allophycocyanin structure from Spirulina platensis as the search model. The
      asymmetric unit contains an (alphabeta) monomer which is expanded by symmetry to
      a crystallographic trimer.

PMID- 18084079
TI  - Structure of Bacillus subtilis superoxide dismutase.
AB  - The sodA gene of Bacillus subtilis was expressed in Escherichia coli, purified
      and crystallized. The crystal structure of MnSOD was solved by molecular
      replacement with four dimers per asymmetric unit and refined to an R factor of
      21.1% at 1.8 A resolution. The dimer structure is very similar to that of the
      related enzyme from B. anthracis. Larger structural differences were observed
      with the human MnSOD, which has one less helix in the helical domain and a longer
      loop between two beta-strands and also showed differences in three amino acids at
      the intersubunit interface in the dimer compared with the two bacterial MnSODs.
      These structural differences can be exploited in the design of drugs that
      selectively target the Bacillus enzymes.

PMID- 18084080
TI  - Hexammineruthenium(III) ion interactions with Z-DNA.
AB  - The hexamer duplex d(CGCGCA).d(TGCGCG) was crystallized with
      hexammineruthenium(III) ions in an orthorhombic space group; the crystals
      diffracted to 1.54 A resolution. Strong ion interactions with the adenine base
      induce a tautomeric shift from the amino to the imino form. Consequently, the A.T
      base pairing is disrupted. This structural study may be relevant to metal
      toxicity.

PMID- 18084081
TI  - Crystallization and preliminary X-ray diffraction studies of the ISC-like [2Fe
      2S] ferredoxin (FdxB) from Pseudomonas putida JCM 20004.
AB  - The iron-sulfur (Fe-S) cluster-biosynthesis (ISC) system of the gamma
      proteobacterium Pseudomonas putida JCM 20004 contains a constitutively expressed
      vertebrate-type [2Fe-2S] ferredoxin, FdxB, which lacks the conserved free
      cysteine residue near the Fe-S cluster site that has been proposed to function in
      the catalysis of biological Fe-S cluster assembly in other bacterial homologues.
      Recombinant FdxB was heterologously overproduced in Escherichia coli, purified
      and crystallized in its oxidized form by the hanging-drop vapour-diffusion and
      streak-seeding methods using 1.6 M trisodium citrate dihydrate pH 6.5. The thin
      needle-shaped crystals diffract to 1.90 A resolution and belong to the hexagonal
      space group P6(1)22, with unit-cell parameters a = 87.58, c = 73.14 A. The
      asymmetric unit contains one protein molecule.

PMID- 18084082
TI  - Crystallization and preliminary X-ray diffraction analysis on the homing
      endonuclease I-Dmo-I in complex with its target DNA.
AB  - Homing endonucleases are highly specific DNA-cleaving enzymes that recognize long
      stretches of base pairs. The availability of these enzymes has opened novel
      perspectives for genome engineering in a wide range of fields, including gene
      therapy, by taking advantage of the homologous gene-targeting enhancement induced
      by a double-strand break. I-Dmo-I is a well characterized homing endonuclease
      from the archaeon Desulfurococcus mobilis. The enzyme was cloned and
      overexpressed in Escherichia coli. Crystallization experiments of I-Dmo-I in
      complex with its DNA target in the presence of Ca(2+) and Mg(2+) yielded crystals
      that were suitable for X-ray diffraction analysis. The crystals belonged to the
      monoclinic space group P2(1), with unit-cell parameters a = 106.75, b = 70.18, c
      = 106.85 A, alpha = gamma = 90, beta = 119.93 degrees . The self-rotation
      function and the Matthews coefficient suggested the presence of three protein-DNA
      complexes per asymmetric unit. The crystals diffracted to a resolution limit of
      2.6 A using synchrotron radiation at the Swiss Light Source (SLS) and the
      European Synchrotron Radiation Facility (ESRF).

PMID- 18084083
TI  - The production and crystallization of the human leukocyte antigen class II
      molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides
      implicated in coeliac disease.
AB  - The major histocompatibility complex (MHC) class II molecules HLA-DQ2 and HLA-DQ8
      are key risk factors in coeliac disease, as they bind deamidated gluten peptides
      that are subsequently recognized by CD4+ T cells. Here, the production and
      crystallization of both HLA-DQ2 and HLA-DQ8 in complex with the deamidated
      gliadin peptides DQ2 alpha-I (PQPELPYPQ) and DQ8 alpha-I (EGSFQPSQE),
      respectively, are reported.

PMID- 18084084
TI  - Protein preparation, crystallization and preliminary X-ray analysis of the C
      terminal domain of human RSK1 serine/threonine protein kinase.
AB  - As a substrate of extracellular signal-related kinase (ERK), the p90 ribosome S6
      kinase 1 (RSK1) is at the terminus of the Ras/ERK pathway. Residues 411-735 of
      human RSK1, covering the C-terminal serine/threonine kinase catalytic domain and
      the functionally important tail, were cloned into an Escherichia coli expression
      vector. The protein was expressed, purified and crystallized. The crystals
      diffracted to 2.7 A and belonged to space group P2(1), with unit-cell parameters
      a = 39.8, b = 143.8, c = 59.9 A, beta = 95.7 degrees.

PMID- 18084085
TI  - An unexpected outcome of surface engineering an integral membrane protein:
      improved crystallization of cytochrome ba(3) from Thermus thermophilus.
AB  - Past work has shown that it is feasible to mutate surface residues of soluble
      proteins and to a lesser extent membrane proteins in order to improve their
      crystallization behavior. Described here is a successful application of this
      approach to the integral membrane protein Thermus thermophilus cytochrome ba(3)
      oxidase. Two mutant forms of this enzyme (I-K258R and I-K258R/II-E4Q) were
      created in which symmetrical crystal contacts within crystals of wild-type enzyme
      were modified. These mutant proteins had greatly shortened crystallization times,
      decreasing from approximately 30 d for the wild type to 1-3 d for the mutants,
      and crystallization was highly reproducible. Native-like proteins crystallize in
      space group P4(3)2(1)2, whereas the mutant proteins crystallize in space group
      P4(1)2(1)2 with a different packing arrangement. Crystals of the P4(3)2(1)2 form
      occasionally diffracted to 2.4-2.3 A resolution following controlled dehydration,
      while those of the P4(1)2(1)2 form routinely diffracted to between 3.0 and 2.6 A
      for crystals that had been cryoprotected but not dehydrated.

PMID- 18084086
TI  - Crystallization and X-ray diffraction analysis of a novel immune-type receptor
      from Ictalurus punctatus and phasing by selenium anomalous dispersion methods.
AB  - X-ray diffraction data from crystals of a novel immune-type receptor (NITR10 from
      the catfish Ictalurus punctatus) were collected to 1.65 A resolution and reduced
      to the primitive hexagonal lattice. Native and selenomethionine derivatives of
      NITR10 crystallized under different conditions yielded P3(1)21 crystals. SeMet
      NITR10 was phased to a correlation coefficient of 0.77 by SAD methods and
      experimental electron-density maps were calculated to 1.65 A. Five NITR10
      molecules are predicted to be present in the asymmetric unit based on the
      Matthews coefficient.

PMID- 18084087
TI  - Crystallization and preliminary X-ray analysis of the HA3 component of
      Clostridium botulinum type C progenitor toxin.
AB  - HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b,
      the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this
      report, recombinant HA3 protein was overexpressed in Escherichia coli, purified
      and crystallized. Diffraction data were collected to 2.6 A resolution and the
      crystal belonged to the hexagonal space group P6(3). Matthews coefficient and
      self-rotation function calculations indicate that there is probably one molecule
      of HA3 in the asymmetric unit. A search for heavy-atom derivatives has been
      undertaken.

PMID- 18084088
TI  - Crystallization and initial crystallographic characterization of a vicilin-type
      seed storage protein from Pinus koraiensis.
AB  - The cupin superfamily of proteins includes the 7S and 11S seed storage proteins.
      Many members of this family of proteins are known allergens. In this study, the
      Korean pine (Pinus koraiensis) vicilin-type 7S seed storage protein was isolated
      from defatted pine-nut extract and purified by sequential gel-filtration and
      anion-exchange chromatography. Well diffracting single crystals were obtained by
      the vapor-diffusion method in hanging drops. The crystals belong to the primitive
      cubic space group P2(1)3, with unit-cell parameters a = b = c = 148.174 A. Two
      vicilin molecules were present in the asymmetric unit and the Matthews
      coefficient was determined to be 2.90 A(3) Da(-1), with a corresponding solvent
      content of approximately 58%. A molecular-replacement structural solution has
      been obtained using the program Phaser. Refinement of the structure is currently
      under way.

PMID- 18084089
TI  - Crystallization and preliminary diffraction studies of CBM3b of cellobiohydrolase
      9A from Clostridium thermocellum.
AB  - Family 3 carbohydrate-binding modules (CBM3s) are associated with the scaffoldin
      subunit of the multi-enzyme cellulosome complex and with the family 9 glycoside
      hydrolases, which are multimodular enzymes that act on plant cell-wall
      polysaccharides, notably cellulose. Here, the crystallization of CBM3b from
      cellobiohydrolase 9A is reported. The crystals are tetragonal and belong to space
      group P4(1) or P4(3). X-ray diffraction data for CBM3b have been collected to
      2.68 A resolution on beamline ID14-4 at the ESRF.

PMID- 18084090
TI  - Crystallization and preliminary X-ray studies of TON_1713 from Thermococcus
      onnurineus NA1, a putative member of the haloacid dehalogenase superfamily.
AB  - The haloacid dehalogenase (HAD) protein superfamily is one of the largest enzyme
      families and shows hydrolytic activity towards diverse substrates. Structural
      analyses of enzymes belonging to the HAD family are required to elucidate the
      molecular basis underlying their broad substrate specificity and reaction
      mechanism. For this purpose, TON_1713, a hypothetical protein from Thermococcus
      onnurineus that is a member of the HAD superfamily, was expressed in Escherichia
      coli, purified and crystallized at 295 K using 1.6 M magnesium sulfate as a
      precipitant. X-ray diffraction data were collected to 1.8 A resolution using a
      synchrotron-radiation source. The crystals belong to the triclinic space group
      P1, with unit-cell parameters a = 52.5, b = 65.8, c = 203.4 A, alpha = 71.1, beta
      = 79.9, gamma = 74.3 degrees.

PMID- 18084091
TI  - Crystallization and preliminary X-ray diffraction analysis of ybfF, a new
      esterase from Escherichia coli K12.
AB  - The product of the recently discovered ybfF gene, which belongs to the esterase
      family, does not show high sequence similarity to other esterases. To provide the
      molecular background to the enzymatic mechanism of the ybfF esterase, the ybfF
      protein from Escherichia coli K12 (Ec_ybfF) was cloned, expressed and purified.
      The Ec_ybfF protein was crystallized from 60% Tacsimate and 0.1 M bis-Tris
      propane buffer pH 7.0. Diffraction data were collected to 1.10 A resolution using
      synchrotron radiation. The crystal belongs to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a = 66.09, b = 90.71, c = 92.88 A. With
      two Ec_ybfF molecules in the asymmetric unit, the crystal volume per unit protein
      weight is 2.17 A(3) Da(-1), corresponding to a solvent content of 42%.

PMID- 18084092
TI  - Expression, purification and crystallization of human 5-lipoxygenase-activating
      protein with leukotriene-biosynthesis inhibitors.
AB  - The nuclear membrane protein 5-lipoxygenase-activating protein (FLAP) plays an
      essential role in leukotriene synthesis. Recombinant full-length human FLAP with
      a C-terminal hexahistidine tag has been expressed and purified from the
      cytoplasmic membrane of Escherichia coli. Diffraction-quality crystals of FLAP in
      complex with leukotriene-synthesis inhibitor MK-591 and with an iodinated
      analogue of MK-591 have been grown using the sitting-drop vapor-diffusion method.
      The crystals exhibit tetragonal symmetry (P42(1)2) and diffracted to a resolution
      limit of 4 A.

PMID- 18084093
TI  - Cloning, expression, purification, crystallization and X-ray crystallographic
      analysis of ScpB (Rv1710) from Mycobacterium tuberculosis.
AB  - Structural maintenance of chromosome (SMC) proteins play diverse roles in
      cellular DNA reassembly by directly interacting with DNA. They require non-SMC
      proteins for their proper function; these include the conserved segregation and
      condensation proteins (Scps) in prokaryotes. ScpB from Mycobacterium tuberculosis
      was crystallized using the sitting-drop vapour-diffusion method in the presence
      of 2 M NaCl and 10% PEG 6000 at 295 K. X-ray diffraction data were collected to a
      maximum resolution of 2.3 A at a synchrotron beamline. The crystal belongs to the
      hexagonal space group R32, with unit-cell parameters a = b = 136.69, c = 78.55 A,
      gamma = 120 degrees . With one molecule per asymmetric unit, the crystal volume
      per unit protein weight (V(M)) is 2.95 A(3) Da(-1). The structure was solved by
      the single anomalous dispersion method and structure refinement is in progress.

PMID- 18084094
TI  - Crystallization and preliminary crystallographic analysis of the Tob-hCaf1
      complex.
AB  - The Tob/BTG family is a group of antiproliferative proteins that contain two
      highly homologous regions named Box A and Box B. These proteins all associate
      with CCR4-associated factor 1 (Caf1), which belongs to the ribonuclease D family
      of deadenylases. The antiproliferative region of human Tob (residues 1-138) and
      intact hCaf1 were co-expressed in Escherichia coli, purified and successfully
      cocrystallized. The crystal belongs to the tetragonal space group I422, with unit
      cell parameters a = b = 150.9, c = 113.9 A, and is estimated to contain one
      heterodimer per asymmetric unit. The crystal diffracted to around 2.6 A
      resolution.

PMID- 18084095
TI  - Crystallization and preliminary X-ray diffraction analysis of ydjA, a minimal
      nitroreductase from Escherichia coli K12.
AB  - Nitroreductases that reduce hazardous nitroaromatic compounds are of interest
      because of their central role in nitroaromatic toxicity, their potential use in
      bioremediation and their utility in activating prodrugs in directed anticancer
      therapies. To provide the molecular background to the enzymatic mechanism of the
      ydjA nitroreductase, which is one of the smallest nitroreductases, the ydjA gene
      from Escherichia coli K12 was cloned and expressed and the expressed protein
      Ec_ydjA was purified. Ec_ydjA was crystallized from 20%(w/v) polyethylene glycol
      1000, 0.2 M lithium sulfate and 0.1 M phosphate-citrate pH 4.2. Diffraction data
      were collected to 2.00 A resolution using synchrotron radiation. The crystal
      belongs to the monoclinic space group C2, with unit-cell parameters a = 87.55, b
      = 129.28, c = 36.88 A, alpha = 90, beta = 103.8, gamma = 90 degrees . With two
      Ec_ydjA molecules in the asymmetric unit, the Matthews coefficient was 2.43 A(3)
      Da(-1) and the solvent content was 48.33%.

PMID- 18084096
TI  - Preliminary X-ray crystallographic studies of a tetrameric phospholipase A2
      formed by two isoforms of crotoxin B from Crotalus durissus terrificus venom.
AB  - Crotoxin B is a basic phospholipase A2 found in the venom of Crotalus durissus
      terrificus and is one of the subunits that constitute crotoxin. This
      heterodimeric toxin, which is the main component of C. d. terrificus venom, is
      completed by an acidic, nontoxic and non-enzymatic component (crotoxin A) and is
      involved in important envenomation effects, such as neurological disorders,
      myotoxicity and renal failure. Although crotoxin was first crystallized in 1938,
      no crystal structure is currently available for crotoxin, crotoxin A or crotoxin
      B. In this work, the crystallization, X-ray diffraction data collection to 2.28 A
      resolution and molecular-replacement solution of a novel tetrameric complex
      formed by two dimers of crotoxin B isoforms (CB1 and CB2) is presented.

PMID- 18084097
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of the
      plant Rho protein ROP5.
AB  - The small G protein ROP5 from the model plant Arabidopsis thaliana was purified
      and crystallized using the hanging-drop vapour-diffusion method. ROP5 crystals
      were obtained using PEG 3000 as precipitant and belong to space group P2(1). A
      data set was collected to 1.53 A resolution using synchrotron radiation at 100 K.
      A clear molecular-replacement solution was found using ROP4-GDP of the ROP4-GDP
      PRONE8 complex as the search model.

PMID- 18084098
TI  - Production, purification and preliminary X-ray crystallographic studies of adeno
      associated virus serotype 7.
AB  - Crystals of baculovirus-expressed adeno-associated virus serotype 7 capsids
      diffract X-rays to approximately 3.0 A resolution. The crystals belong to the
      rhombohedral space group R3, with unit-cell parameters a = 252.4, c = 591.2 A in
      the hexagonal setting. The diffraction data were processed and reduced to an
      overall completeness of 79.0% and an R(merge) of 12.0%. There are three viral
      capsids in the unit cell. The icosahedral threefold axis is coincident with the
      crystallographic threefold axis, resulting in one third of a capsid (20 monomers)
      per crystallographic asymmetric unit. The orientation of the viral capsid has
      been determined by rotation-function searches and is positioned at (0, 0, 0) by
      packing considerations.

PMID- 18084099
TI  - Crystallization and preliminary X-ray diffraction analysis of the small laccase
      from Streptomyces coelicolor.
AB  - The small bacterial laccase from the actinobacterium Streptomyces coelicolor
      which lacks the second of the three domains of the laccases structurally
      characterized to date was crystallized. This multi-copper phenol oxidase
      crystallizes in a primitive tetragonal lattice, with unit-cell parameters a = b =
      179.8, c = 175.3 A. The crystals belong to either space group P4(1)2(1)2 or
      P4(3)2(1)2. The self-rotation function shows the presence of a
      noncrystallographic threefold axis in the structure. Phases will be determined
      from the anomalous signal of the natively present copper ions.

PMID- 18084100
TI  - Preliminary neutron and ultrahigh-resolution X-ray diffraction studies of the
      aspartic proteinase endothiapepsin cocrystallized with a gem-diol inhibitor.
AB  - Endothiapepsin has been cocrystallized with the gem-diol inhibitor PD-135,040 in
      a low solvent-content (39%) unit cell, which is unprecedented for this enzyme
      inhibitor complex and enables ultrahigh-resolution (1.0 A) X-ray diffraction data
      to be collected. This atomic resolution X-ray data set will be used to deduce the
      protonation states of the catalytic aspartate residues. A room-temperature
      neutron data set has also been collected for joint refinement with a room
      temperature X-ray data set in order to locate the H/D atoms at the active site.

PMID- 18084101
TI  - Purification, crystallization and preliminary structural analysis of nucleoside
      diphosphate kinase from Bacillus anthracis.
AB  - Bacillus anthracis nucleoside diphosphate kinase (BaNdk) is an enzyme whose
      primary function is to maintain deoxynucleotide triphosphate (dNTP) pools by
      converting deoxynucleotide diphosphates to triphosphates using ATP as the major
      phosphate donor. Although the structures of Ndks from a variety of organisms have
      been elucidated, the enzyme from sporulating bacteria has not been structurally
      characterized to date. Crystals of the B. anthracis enzyme were grown using the
      vapour-diffusion method from a hanging drop consisting of 2 microl 10 mg ml(-1)
      protein in 50 mM Tris-HCl pH 8.0, 50 mM NaCl, 5 mM EDTA equilibrated against 500
      microl reservoir solution consisting of 2.25 M ammonium formate and 0.1 M HEPES
      buffer pH 7.25. Diffraction data extending to 2.0 A were collected at room
      temperature from a single crystal with unit-cell parameters a = b = 107.53, c =
      52.3 A. The crystals are hexagonal in shape and belong to space group P6(3)22.
      The crystals contain a monomer in the asymmetric unit, which corresponds to a
      Matthews coefficient (V(M)) of 2.1 A(3) Da(-1) and a solvent content of about
      36.9%.

PMID- 18084102
TI  - Crystallization, data collection and processing of the chymotrypsin-BTCI-trypsin
      ternary complex.
AB  - A ternary complex of the black-eyed pea trypsin and chymotrypsin inhibitor (BTCI)
      with trypsin and chymotrypsin was crystallized by the sitting-drop vapour
      diffusion method with 0.1 M HEPES pH 7.5, 10%(w/v) polyethylene glycol 6000 and
      5%(v/v) 2-methyl-2,4-pentanediol as precipitant. BTCI is a small protein with 83
      amino-acid residues isolated from Vigna unguiculata seeds and is able to inhibit
      trypsin and chymotrypsin simultaneously by forming a stable ternary complex. X
      ray data were collected from a single crystal of the trypsin-BTCI-chymotrypsin
      ternary complex to 2.7 A resolution under cryogenic conditions. The structure of
      the ternary complex was solved by molecular replacement using the crystal
      structures of the BTCI-trypsin binary complex (PDB code 2g81) and chymotrypsin
      (PDB code 4cha) as search models.

PMID- 18084104
TI  - The doctor was surprised; or, how to diagnose a miracle.
AB  - A survey of more than six hundred miracle records in the canonization files of
      the Vatican Secret Archives from the seventeenth century to the twentieth century
      reveals that more than 95 percent are healings from illness. The history of the
      canonization process is summarized to explain the sources. The diagnoses amenable
      to miracle cure change through time to reflect current medical preoccupations and
      methods. Physician testimony has always been crucial to the investigation of
      miracles for declaring the hopeless prognosis and the surprise at recovery. From
      this analysis, medicine and religion emerge as parallel semiotic endeavors, using
      their canons of wisdom and careful observation to derive meaning in suffering.

PMID- 18084105
TI  - Lying-in and laying-out: fetal health and the contribution of midwifery.
AB  - This article considers the quality of midwifery skills and practice principally
      in eighteenth-, nineteenth-, and early twentieth-century England. It discusses
      the merits of assessing effectiveness via differentials and changes in late-fetal
      rather than maternal mortality. Evidence from the lying-in hospitals, both in
      patients and out-patients, in terms of stillbirths and the deaths of mothers and
      children is set against what is known from demographic studies of the background
      levels of early-age and maternal mortality. The conclusions emphasize the value
      of taking a "fetal health" perspective, rather than viewing midwifery simply in
      terms of maternal well-being. They also note the apparent superiority of London's
      position compared with the provinces and the steady improvement during the
      eighteenth century, and lack of progress during the nineteenth; and they
      reconfirm the particular dangers to mothers delivered as hospital in-patients.
      Finally, the considerable methodological problems faced by such studies are
      emphasized.

PMID- 18084106
TI  - Scientific method for medical practitioners: the case method of teaching
      pathology in early twentieth-century Edinburgh.
AB  - The appointment of James Lorrain Smith as first full-time professor of pathology
      at the University of Edinburgh in 1912 led to a series of reforms in pathology
      teaching there. Most significant was the inception of what Lorrain Smith called
      the "case method of teaching pathology," which used the investigation of clinical
      cases as the basis for a series of exercises in clinico-pathological correlation.
      This paper examines the social and cognitive organization of the case method of
      teaching, and shows how such exercises were expected to inform the students'
      future medical training and practice. In so doing, it also throws light on the
      relationship between medical science and clinical practice that obtained in
      Edinburgh at that time.

PMID- 18084107
TI  - Biotypology, endocrinology, and sterilization: the practice of eugenics in the
      treatment of Argentinian women during the 1930s.
AB  - This article looks at medical approaches to women's fertility in Argentina in the
      1930s and explores the ways in which eugenics encouraged the reproduction of the
      fit and attempted to avoid the reproduction of the unfit. The analysis
      concentrates on three main aspects: biotypology (the scientific classification of
      bodies), endocrine therapy, and sterilization. The article concludes by
      suggesting that a eugenically oriented obstetrical and gynecological practice
      encouraged both endocrine treatments (to achieve the ideal fertile woman) and
      sterilization, which, in spite of being legally banned, found a subtle
      application.

PMID- 18084108
TI  - Clinician and revolutionary: Frantz Fanon, biography, and the history of colonial
      medicine.
AB  - Although scholars have exhibited close interest in the life and work of Frantz
      Fanon, few have emphasized his work as a psychiatrist. This essay surveys recent
      books and films that have placed Fanon's clinical experience at the center of his
      life's work. It concludes that historians of colonial medicine have much to gain
      from these works and their reexaminations of a controversial figure.

PMID- 18084115
TI  - Dysphagia in adult Japanese is not equivalent to the grade of endoscopic reflux
      esophagitis.
AB  - OBJECTIVE: This study was aimed to evaluate the correlation between dysphagia,
      detected by nursing staff in a brief interview and endoscopic findings in reflux
      esophagitis. PATIENTS AND METHODS: A total of 8,031 Japanese subjects without
      medication for gastrointestinal disease were briefly asked about the presence of
      heartburn, dysphagia, odynophagia, and acid regurgitation by nursing staff before
      endoscopy for assessment of esophagitis utilizing the Los Angeles Classification.
      RESULTS: The grade of endoscopic esophagitis was not equivalent to symptoms of
      dysphagia in 8,031 subjects. We evaluated the characteristics of subjects who
      complained of only dysphagia. Univariate analysis indicated that non-smoking, and
      non-drinking females were associated with a higher risk for dysphagia, and
      multivariate analysis indicated the gender was associated with dysphagia. There
      was no association of dysphagia with herniation and distribution of age.
      CONCLUSION: This study indicated that dysphagia was not equivalent to the
      endoscopic findings according to a brief interview by nursing staff and that
      dysphagia might be more common in females and those who do not smoke or drink.

PMID- 18084114
TI  - Clinical features of Japanese elderly patients with type 1 autoimmune hepatitis.
AB  - OBJECTIVE: In Caucasian type 1 autoimmune hepatitis patients with a main
      susceptibility of human leukocyte antigen DR3 and DR4, elderly patients have a
      higher frequency of concurrent autoimmune disease and cirrhosis at presentation.
      However, in Japanese patients, the disease is dominantly associated with DR4, and
      their clinical features may be different from those of previous reports. In this
      study, we assessed the clinical features of Japanese elderly patients with type 1
      autoimmune hepatitis. METHODS: We investigated 160 consecutive patients with type
      1 autoimmune hepatitis, consisting of 34 elderly patients (> or = 65 years) and
      126 younger patients (< 65 years). RESULTS: There were no differences in form of
      clinical onset, frequencies of concurrent autoimmune disease, positive
      proportions of anti-nuclear antibody and/or anti-smooth muscle antibody, and
      human leukocyte antigen DR status between the two groups. However, the elderly
      patients had lower serum levels of albumin (p=0.0049), and higher frequencies of
      cirrhosis (F4) and pre-cirrhosis (F3) (p=0.014) compared with the younger
      patients. In contrast, in elderly patients, the cumulative incidental rate of the
      normalization of serum alanine aminotransferase levels within 6 months after the
      introduction of initial treatment was higher in those treated with prednisolone >
      or = 20 mg/day than those treated only with ursodeoxycholic acid (p=0.001).
      CONCLUSION: We speculate that more years may pass between the occurrence of the
      disease and the presentation in Japanese elderly patients than in younger
      patients, and we considered that, even in elderly patients, those with advanced
      fibrosis should be treated with prednisolone in order to prevent progress of the
      disease into liver failure.

PMID- 18084116
TI  - "Type 1 on type 2" diabetes mellitus: autoimmune type 1 diabetes superimposed on
      established type 2 diabetes.
AB  - OBJECTIVE: To investigate clinical features and pathophysiology of a rare form of
      new-onset type 1 diabetes mellitus that was superimposed on established type 2
      diabetes. PATIENTS AND METHODS: We retrospectively analyzed 126 consecutive type
      2 diabetic patients, who were admitted to the hospital 2 or more times from July
      2000 to December 2005 and had been repeatedly examined for islet-associated
      autoantibodies and insulin secretory capacity over a period of years. RESULTS: We
      experienced 2 patients in whom autoantibodies including ICA, GADAb, and IA-2Ab
      were initially all negative, but in whom at least 1 of these antibodies later
      became positive, whose endogenous insulin secretion decreased, and who eventually
      reached an insulin-dependent stage. At the time of seroconversion of antibodies,
      the patients had 15 to 23 years' history of diabetes, and had microvascular
      complications specific to diabetes mellitus, and before seroconversion insulin
      secretory capacities were preserved. The patients had HLA types associated with
      susceptibility to Japanese type 1 diabetes mellitus. CONCLUSIONS: Our findings
      suggest that autoimmune type 1 diabetes mellitus may be superimposed on well
      established type 2 diabetes.

PMID- 18084117
TI  - Investigation of microalbuminuria in nondiabetic, normotensive obese women.
AB  - AIM: To investigate if obesity which is not accompanied by diabetes and/or
      hypertension is associated with microalbuminuria in female patients. MATERIALS
      AND METHODS: A total of 77 obese female patients from the Outpatient Clinic of
      Endocrinology of Istanbul University Cerrahpasa Medical Faculty and 30 age
      matched, lean, healthy women were enrolled in the study. Patients with
      accompanying diabetes mellitus, hypertension, obesity associated with any
      endocrine abnormality, hepatic or renal disease, fever, infectious disease,
      malignancy were excluded. Weight, height, body-mass index (BMI), waist
      circumference, waist/hip ratio (WHR) and systolic and diastolic blood pressures
      were recorded. Albumin excretion in 24-hour urine samples (UAE) were measured
      using SYNCHRON LX System with MA Microalbumin kit in two separate 24-hour urine
      samples from every patient. Statistical analysis was performed using t-test and
      Pearson's correlation in SPSS 12.0 for Windows Program. RESULTS: The median
      albumin excretion in 24-hour urine sample was similar in obese and control groups
      (12.01 +/- 10.69 mg/day vs 9.35 +/- 4.09 mg/day; p= 0.211). There were no
      correlations between the albumin excretion in 24 hour urine samples and BMI,
      waist circumference, WHR, systolic or diastolic blood pressure. CONCLUSION:
      Diabetes mellitus and hypertension are known to be associated with
      microalbuminuria. In our study, microalbuminuria was not detected in obese women
      without diabetes and/or hypertension and UAE was similar in obese and lean women.

PMID- 18084118
TI  - Short-term effects of pitavastatin on biochemical markers of bone turnover in
      patients with hypercholesterolemia.
AB  - OBJECT: No consensus has been reached whether clinical use of statins has
      beneficial effects on bone health, partly due to lower statin concentrations
      because of first-pass metabolism by the liver. We thus evaluated the effects of
      pitavastatin, which does not undergo first-pass metabolism, on bone metabolism.
      METHODS: According to the therapeutic regimen, the subjects were divided into two
      groups (group A, 66 with pitavastatin; group B, 35 without pitavastatin). Bone
      specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I
      collagen (NTx) as bone turnover markers (BTMs) were compared between the two
      groups and between at baseline and after 3 months of treatment in each group.
      Correlations between baseline characteristics and deltaBTMs, and between delta
      lipid profile and deltaBTMs were investigated using both Pearson's correlation
      analysis and multivariate analysis. PATIENTS: The subjects were 101 patients with
      untreated hypercholesterolemia. RESULTS: After 3 months of treatment, BAP in
      group A did not change significantly compared with either the baseline value or
      that in group B. However, NTx in group A significantly decreased compared with
      both the baseline value and that in group B. In addition, deltaNTx was negatively
      correlated with NTx at baseline, and the significance of this correlation
      persisted after multiple regression analysis. CONCLUSION: Our findings suggest
      that pitavastatin may have potentially beneficial effects on bone metabolism
      primarily by reducing bone resorption rather than by stimulating bone formation.
      Further studies with more patients and longer duration are warranted to evaluate
      its effects, if any, on prevention of osteoporosis and subsequent fractures.

PMID- 18084119
TI  - Symptoms associated with parvovirus B19 infection in adults: a pilot study.
AB  - BACKGROUND AND OBJECTIVES: The clinical features of parvovirus B19 infection in
      adult patients have not been well described. The aim of this prospective study
      was to clarify the clinical features of adult patients with parvovirus B19
      infection in primary care settings. METHODS: The study subjects were adults over
      age 18 years who had visited one primary care clinic over a period of one year.
      They were chosen if they had at least two of the following three symptoms: edema,
      joint pain, and rash, and if they had contact with children with erythema
      infectiosum. The diagnosis was confirmed if anti-parvovirus B19 antibodies were
      identified. The process of these symptoms was recorded until they resolved.
      RESULTS: Twenty patients met the inclusion criteria, and 14 (70%) patients were
      diagnosed with parvovirus B19 infection. The 14 adult patients consisted of two
      men and twelve women ranging from 33 to 63 years (median, 38 years). The patients
      consisted of two groups. In the first group, they presented with the first phase
      of infection showing symptoms such as malaise, muscle pain, and fever, and in the
      second phase presented with edema, rash, and joint pain that developed within two
      days of the first phase. In the second group, the first and second phases were
      clearly separated. CONCLUSIONS: Parvovirus B19 infection in adults can be
      efficiently diagnosed in primary care settings by observing clinical symptoms
      such as edema, joint pain, and rash, and by asking patients about their contact
      with children who have erythema infectiosum.

PMID- 18084120
TI  - Duodenal duplication cyst of the ampulla of Vater.
AB  - A 35-year-old man presented with the complaint of epigastric discomfort.
      Gastrointestinal endoscopy and endoscopic ultrasonography revealed a cystic
      lesion 20 mm in size at the ampulla of Vater. Endoscopic retrograde
      cholangiopancreatography (ERCP) revealed that the cystic lesion communicated with
      both the common bile duct and pancreatic duct via the common channel.
      Choledochocele was ruled out by close examination of the ERCP findings. The
      cystic lesion was surgically resected. Since histological findings revealed that
      the mucosa inside the lesion was duodenum-like and contained a layer of smooth
      muscle, the lesion was diagnosed as a congenital duplication cyst of the
      duodenum.

PMID- 18084121
TI  - IgG4-related autoimmune prostatitis: two cases with or without autoimmune
      pancreatitis.
AB  - Recently, autoimmune pancreatitis (AIP) has been reported with a variety of extra
      pancreatic manifestations and infiltration of IgG4-positive cells into the
      affected organs. We report herein two cases with prostatitis. One was seen in a
      patient with typical AIP, and the other was observed without any clinical
      manifestation of AIP. Serum IgG4 levels were elevated in both cases. Histological
      examination of the prostates showed that parenchymal cells were partially or
      totally replaced with fibrosis and abundant infiltration of IgG4-positive cells.
      Significant uptake of [18F] fluorodeoxyglucose by the prostate was seen in both
      cases. In the case with AIP, the uptake completely disappeared after steroid
      therapy. The findings observed in these cases suggest that the pathological
      mechanism for prostatitis is similar to the mechanism previously implicated in
      AIP, namely IgG4-related autoimmune prostatitis.

PMID- 18084122
TI  - Coronary slow flow phenomenon caused by contrast-induced microvascular spasm.
AB  - Coronary slow flow phenomenon is not an infrequent finding and is often
      associated with chest pain, but the mechanism has not been fully elucidated. We
      report a case of coronary slow flow phenomenon induced after contrast injection
      which was resolved by nicorandil administration. Therefore, the microvascular
      spasm might be an important factor in coronary slow flow phenomenon and contrast
      medium can be a trigger.

PMID- 18084123
TI  - A Japanese family of typical Loeys-Dietz syndrome with a TGFBR2 mutation.
AB  - This report describes a Japanese family with vessel and craniofacial
      abnormalities. Although the clinical findings of the patient's father fulfilled
      the diagnostic criteria for Marfan syndrome, arterial tortuosity, aneurysms,
      hypertelorism and a bifid uvula were noted in both the patient and his father.
      These findings were compatible with the clinical manifestations that were
      previously reported in Loeys-Dietz syndrome. A molecular genetic analysis
      demonstrated a heterozygous missense mutation of the transforming growth factor
      beta receptor II gene in both the patient and his father, which thus caused Loeys
      Dietz syndrome. This is the first Japanese family case report of typical Loeys
      Dietz syndrome.

PMID- 18084124
TI  - Biopsy-proven tuberculous meningitis mimicking CNS sarcoidosis.
AB  - We report a 31-year-old man with tuberculous meningitis (TM) mimicking CNS
      sarcoidosis. Although Mycobacterium tuberculosis (MTB) was not detected in CSF,
      the level of adenosine deaminase (ADA) in CSF was significantly raised. Brain
      biopsy showed caseous granuloma and a diagnosis of TM was made. The diagnosis of
      TM is often difficult and brain biopsy should be considered if MTB is not
      detected in the CSF. Evaluation of CSF ADA level could also strongly contribute
      to distinguishing TM from other meningitis. In addition to antituberculosis
      drugs, corticosteroid therapy was effective in our patient but careful reduction
      of its dosage was required.

PMID- 18084125
TI  - Noninvasive ventilation in Plasmodium vivax related ALI/ARDS.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS),
      complications of P. falciparum malaria are associated with a very high mortality
      but are rarely seen in P. vivax malaria. Herein, we report a 28-year old woman
      who developed ARDS after infection with P. vivax. In a systematic review the
      literature for the use of noninvasive ventilation (NIV) in cases of ALI/ARDS
      related to P. vivax, from among 45 reports noninvasive positive pressure
      ventilation (NIPPV) was used in the management of three cases of ALI/ARDS related
      to P. vivax. The use of NIV in vivax malaria related ALI/ARDS is associated with
      a good outcome.

PMID- 18084126
TI  - Three cases of liver abscesses complicated with colon cancer without liver
      metastasis: importance of screening for digestive disease.
AB  - We treated 3 patients complicated with colon cancer without liver metastasis, who
      were admitted to our hospital because of a high fever and diagnosed with liver
      abscesses. In a general screening after performing percutaneous transhepatic
      abscess drainage, colon cancer was detected in each, though hepatobiliary
      diseases were not found. Hepatobiliary diseases were the most common etiology of
      hepatic abscesses in our hospital in the past 41 cases from 1990 to 2005, 3 of
      which were due to colon cancer. If a cause is not determined, general screening,
      especially of the colon tract, should be performed in hepatic abscesses patients.

PMID- 18084127
TI  - Systemic sarcoidosis associated with double cancers of the esophagus and stomach.
AB  - To discriminate between sarcoidosis and sarcoid reaction in the lymphadenopathy
      of malignancy is sometimes clinically important. We describe a case of
      sarcoidosis associated with double cancers of the esophagus and stomach. A
      patient who six months previously was found to have early gastric cancer, was
      then found to have esophagus cancer. The chest radiography demonstrated bilateral
      hilar lymphadenopathy. Pathological analysis of the lymph nodes and lungs showed
      non-caseating epithelioid cell granuloma, revealing the existence of sarcoidosis.
      The findings suggest that the possibility of systemic sarcoidosis should be
      considered in cases with established malignancy and newly disclosed radiographic
      findings.

PMID- 18084129
TI  - Easier understanding of pleural indentation on computed tomography.

PMID- 18084128
TI  - Post-colonoscopic Listeria septicemia in ulcerative colitis during
      immunosuppressive therapy.
AB  - A 78-year-old man who had been diagnosed with ulcerative colitis was admitted
      because of uncontrolled severe, frequent, bloody diarrhea. He was treated with
      immunosuppressive therapy that included corticosteroid and azathioprine.
      Colonoscopy was used to assess disease activity. This revealed that the mucosa of
      his digestive tract from the rectum to the ileum was damaged. He developed a high
      grade fever soon after colonoscopy. Blood culture demonstrated Listeria
      monocytogenes. Treatment was changed to intravenous ampicillin for 20 days. His
      general body symptoms, including the bloody diarrhea, improved after treatment.
      We assume that the colonoscopy induced Listeria monocytogenes septicemia through
      bacterial translocation in this patient.

PMID- 18084130
TI  - Abnormal centrosome amplification and Aurora-A activation in p53-deficient cells.

PMID- 18084131
TI  - Useful tips for successful skin grafting.
AB  - Skin grafting is a common operative method widely used in the field of plastic,
      reconstructive, and aesthetic surgery. However, we offer five suggestions to
      reduce complications and surgical invasiveness. Our tips are as follows. (1) Skin
      grafts should be harvested on the basis of a swimsuit with high-cut leg openings.
      (2) A drum dermatome is still useful when a split-thickness skin graft is needed
      after a full-thickness graft has been harvested. (3) A flower holder is useful
      for making drainage holes. (4) A tie-over dressing using external wire-frame
      fixation is recommended. (5) Povidone-iodine gel is recommended with a tie-over
      dressing. These procedures have been found to be extremely helpful for ensuring
      the success of skin-grafting procedures.

PMID- 18084132
TI  - Repair of an infrarenal abdominal aortic aneurysm is associated with persistent
      left ventricular diastolic dysfunction.
AB  - BACKGROUND: Left ventricular (LV) diastolic function has received much attention
      recently. However, few studies have evaluated LV diastolic function in the
      perioperative period. The aim of this study was to elucidate perioperative
      changes in diastolic function using tissue Doppler imaging (TDI) in patients
      undergoing repair of an infrarenal abdominal aortic aneurysm (AAA). METHODS:
      Eight patients undergoing repair of an infrarenal AAA were studied prospectively
      using transesophageal echocardiography. Doppler echocardiographic examinations
      were performed before the surgical procedure (T1), immediately before aortic
      unclamping (T2), 30 minutes after aortic unclamping (T3), and at the end of
      surgery (T4). RESULTS: Pulmonary edema developed in two patients on postoperative
      day 1. These two patients had the lowest early diastolic mitral annular velocity
      (Ea) of the study group at the end of surgery. The ratio of the peak velocity of
      early mitral inflow (E) to the peak velocity of atrial inflow was significantly
      decreased at T3 and T4. The systolic ejection velocity was significantly
      decreased at T3, but returned to the baseline value at T4. The Ea was
      significantly decreased at T3 and T4. The E/Ea ratio showed a progressive rise
      and was significantly increased at T3 and T4. CONCLUSIONS: In patients undergoing
      repair of an infrarenal AAA, the Ea derived using TDI decreases at T3 and is
      still reduced at T4. The E/Ea ratio, which is used to estimate LV filling
      pressures, is significantly increased at T3 and T4. Further research is required
      to confirm the development of diastolic dysfunction and determine its possible
      association with increased postoperative morbidity and mortality.

PMID- 18084133
TI  - Cross-cultural validation of the Japanese version of the lung cancer subscale on
      the functional assessment of cancer therapy-lung.
AB  - BACKGROUND: The Functional Assessment of Cancer Therapy-Lung (FACT-L)
      questionnaire, which consists of a core questionnaire (the General Measure of
      FACT [FACT-G]) and a 9-item Additional Concerns comprised of a 7-item Lung Cancer
      Subscale (LCS), was developed in an English-speaking culture. The validation of
      the Japanese FACT-G was reported previously, and this report describes the cross
      cultural validation of the LCS. METHODS: The Japanese version of the LCS was
      developed through an iterative forward-backward translation sequence used
      throughout the FACT Multilingual Translation Project. In evaluating psychometric
      performance, its construct validity was investigated with Cronbach's alpha
      coefficient and factor analysis. Clinical validities of a known-groups comparison
      and longitudinal validity were also investigated. RESULTS: The FACT-L was
      administered twice to 180 patients with lung cancer within 2 weeks. The Japanese
      LCS had borderline values for Cronbachs alpha coefficients (0.62-0.67). Factor
      analysis indicated that the LCS had the three dimensions of respiratory symptoms,
      appetite plus body weight, and clear thinking. For clinical validity, a known
      groups comparison showed that the LCS could differentiate patients according to
      truth disclosure, as Japanese doctors sometimes do not fully inform terminally
      ill patients. However, responsiveness was not proved when performance status was
      used as an anchor, probably owing to the short interval between the
      administration of the two measures. CONCLUSION: The Japanese version of the LCS
      asked questions about multiple symptoms of patients with lung cancer, as did the
      original English LCS. The longitudinal clinical validity of the Japanese version
      should be investigated in future clinical trials.

PMID- 18084134
TI  - Evaluation of the clinical pathway for laparoscopic cholecystectomy and
      simulation of short-term hospitalization.
AB  - The effectiveness of the clinical pathway for laparoscopic cholecystectomy was
      evaluated, and the efficiency of medical care was analyzed. The duration of
      hospitalization and the number of National Health Insurance (NHI) points for
      medical service fees were compared between 86 patients treated after introduction
      of the clinical pathway (pathway group) and 56 patients treated before
      introduction of the clinical pathway (pre-pathway group). In the pathway group,
      variance from the pathway occurred in 24 patients (27.9%) due to postponement of
      discharge in 7 patients, to earlier discharge in 5 patients, and to insertion of
      a bile duct catheter in 5 patients. Total and postoperative hospitalization times
      were significantly shorter in the pathway group than in the pre-pathway group
      (8.0 +/- 1.6 vs 13.7 +/- 9.0 days, p<0.0001, 5.4 +/- 1.1 vs 6.5 +/- 2.2 days,
      p<0.0001, respectively). In the pathway group, the total number of NHI points was
      lower and the number of points per day was higher. By simulation, the total
      number of NHI points for the 5-day pathway (discharge on postoperative day 3 or
      earlier) was significantly lower than that for the current 7-day pathway.
      Moreover, the weekly profit per bed with the 3-day pathway (discharge on
      postoperative day 1) was more than twice that with the current pathway. The
      results suggest that the clinical pathway for laparoscopic cholecystectomy is
      beneficial for patients and useful for the introduction of diagnosis procedure
      combination in our hospital.

PMID- 18084135
TI  - Risk factors for postpartum hemorrhage after vaginal delivery of twins.
AB  - We examined vaginal deliveries of twins to identify factors most strongly
      associated with the increased risk of postpartum hemorrhage (estimated blood loss
      > or = 1,000 mL). We reviewed the obstetric records of all 171 twin vaginal
      deliveries at Japanese Red Cross Katsushika Maternity Hospital from January 2002
      through August 2006. Of these deliveries, 41 (24%) were complicated by
      postopartum hemorrhage. Postpartum hemorrhage was significantly more likely in
      cases with gestational age > or = 39 weeks (odds ratio [OR], 3.47; 95% confidence
      interval [CI], 1.65-7.28), a combined birth weight of more than 5,500 g (OR,
      2.53; 95% CI, 1.00-6.45), induction of labor (OR, 2.87; 95% CI, 1.38-5.98),
      oxytocin administration during labor (OR, 2.86; 95% CI, 1.27-6.48), or a duration
      of labor > or = 24 hours (OR, 2.55; 95% CI, 1.15-5.62). Postpartum hemorrhage is
      a frequent complication in twin pregnancies. Therefore, special attention should
      be given after birth to patients with induction of labor or intervened delivery
      especially at > or = 39 weeks gestation.

PMID- 18084136
TI  - An improvement in the quality of life after performing endoscopic balloon
      dilation for postoperative anastomotic stricture of the rectum.
AB  - A 55-year-old woman underwent a low anterior resection for rectal cancer 7 years
      earlier at a different hospital. Thereafter, she often had such symptoms as
      abdominal pain, frequent bowel movements, and constipation. We considered
      postoperative bowel adhesion to be the cause of these symptoms, and a
      laparoscopic adhesiotomy was therefore performed twice. However, the symptoms did
      not substantially improve thereafter. A colonoscope of conventional diameter
      could barely pass through the anastomotic site of the operation, but we initially
      judged the anastomotic stricture to not be severe. However, we finally determined
      the anastomotic stricture to be the cause of these symptoms; X-ray examinations
      frequently showed the blockage of feces or the collection of gas images in the
      colon when the symptoms occurred. We therefore performed endoscopic balloon
      dilation (EBD) after performing electroincision of the scar tissue of the
      anastomotic ring. We dilated the area of the lesion to a diameter of 20 mm using
      the EBD technique, and thereafter the patient finally showed an improvement in
      quality of life. There have been some reports describing the usefulness of EBD
      for the treatment of colorectal anastomotic stricture. Past studies have reported
      the indications of EBD to include stricture, which is defined as a narrowed
      anastomosis through which a 12-mm-diameter colonoscope cannot be passed.
      Nevertheless, it seemed that when the clinical manifestations of anastomotic
      stricture are clear, such as those observed in our case, we should not too
      strictly adhere to this definition.

PMID- 18084137
TI  - Umbilical-cord blood cell transplantation conditioned with a reduced intensity
      regimen is a practical salvage therapy for severe aplastic anemia refractory to
      immunosuppressive therapy with antithymocyte globulin/ciclosporin.
AB  - Immunosuppressive therapy and stem cell transplantation from an HLA-identical
      donor are the major effective treatments for severe aplastic anemia. However,
      treatments still need to be developed for patients who do not have a HLA
      identical donor and have not shown a clinical response to immunosuppressive
      therapy. We herein report on 2 patients in whom this problem could be overcome by
      transplantation of HLA-mismatched umbilical cord blood from unrelated donors. Two
      Japanese patients with severe aplastic anemia underwent conditioning with
      fludarabine, cyclophosphamide, and low-dose total-body irradiation and then
      received transplants of umbilical cord blood. Engraftment of the three lineages
      occurred without problems. We conclude that umbilical cord blood transplantation
      with a reduced-intensity conditioning regimen of fludarabine, cyclophosphamide,
      and total-body irradiation for patients with aplastic anemia is a practical
      treatment and may be an attractive alternative for patients who does not have an
      HLA-identical donor and have shown no clinical response to immunosuppressive
      therapy.

PMID- 18084138
TI  - A case of multiple gastric carcinoids that could not be preoperatively diagnosed.
AB  - Here, we report the case of patient with multiple gastric carcinoids showing
      histopathological behavior similar to that of type I carcinoid tumors of the
      stomach. The patient was a 61-year-old man diagnosed as having a gastric tumor,
      which was revealed by follow-up computed tomography. Upper gastrointestinal
      endoscopy revealed a protruded tumor in the greater curvature and a small polyp
      in the anterior wall of the upper stomach. A biopsy revealed gastric carcinoid.
      Because he refused to be operated for gastric carcinoid, upper gastrointestinal
      endoscopy was performed 5 months later. A malignant transformation of the gastric
      carcinoid was strongly suspected. Therefore, the patient was admitted for
      operation. Laboratory findings were normal. With the diagnosis of type III
      gastric carcinoid, total gastrectomy was performed. Microscopic examination
      revealed that the carcinoid tumor was confined to the submucosa and that the
      small polyp mentioned earlier was also a carcinoid. Microcarcinoids and numerous
      enterochromaffin-like cell hyperplasias were observed along the muscularis
      propria of the fundus. The tumor differed from typical type I gastric carcinoids
      in several ways. Immunohistochemical staining for chromogranin A, synaptophysin,
      and cytokeratin was positive. However, p53 was absent, and the MIB-1 index was
      low. Two years after surgery, the patient is alive without recurrence.

PMID- 18084139
TI  - T helper 1/t helper 2 cell immunity in preeclamptic twin pregnancy.
AB  - Preeclampsia has been classified into two types on the basis of the T helper
      (Th)1/Th2 balance: Th1-predominant type and Th2 predominant type. In this study,
      we examined the Th1/Th2 ratio in peripheral Th cells in 11 patients with
      preeclamptic twin pregnancies, 11 normal (nonpreeclamptic) twin pregnancies, 11
      preeclamptic singleton pregnancies, and 11 normal singleton pregnancies. The
      average Th1/Th2 ratio in the patients with preeclamptic twin pregnancy was 8.3 +/
      3.4 (mean +/- SD), which was similar to those in patients with normal singleton
      and twin pregnancies and significant lower than that in patients with
      preeclamptic singleton pregnancies (p = 0.003). The present results suggest that
      the mechanisms of preeclampsia differ between singleton and twin pregnancies.

PMID- 18084140
TI  - [Importance of repeat laterally directed sextant prostate biopsy for detection of
      prostate cancer in high-risk patients].
AB  - Our purpose was to evaluate the relevance of repeat laterally directed sextant
      prostate biopsy for detection of prostate cancer in high-risk patients. MATERIAL
      AND METHODS: Our study included 195 men at high risk for prostate cancer
      (elevated prostate-specific antigen level and/or abnormal prostate detected by
      digital rectal examination). We consulted the patients in outpatient department
      of Kaunas University of Medicine Hospital during 2003-2007. We performed
      transrectal ultrasound-guided laterally directed sextant prostate biopsy in every
      patient. For the patients with benign histological findings and increased risk of
      prostate cancer, laterally directed sextant biopsies were repeated. RESULTS:
      Prostate cancer was detected in 30.3% of patients (59/195) on the first prostate
      biopsy, in 13.1% (11/84) on the second prostate biopsy, in 10.3% (4/39) on the
      third, and in 7.7% (1/13) on the forth biopsy. After all biopsies, prostate
      cancer was detected in 38.5% (75/195) of patients, and it differed significantly
      from the percentage of prostate cancer cases detected on the first biopsy (30.3%,
      P=0.04). We detected 78.7% (59/75) of all prostate cancer cases by the first
      laterally directed sextant prostate biopsy. The rest 21.3% (16/75) of cases we
      detected by repeat biopsies. The second laterally directed sextant prostate
      biopsy revealed additional 14.6% (n=11) of prostate cancer cases and increased
      the detection of prostate cancer to 93.3% (70/75). At the time of the first
      prostate biopsy, prostate cancer was diagnosed most frequently when patients had
      both risk factors: elevated prostate-specific antigen level and abnormal digital
      prostate examination; prostate cancer was diagnosed in 45.3% of these patients.
      The odds ratio to detect prostate cancer by the first biopsy in patients with
      elevated prostate-specific antigen level and abnormal digital prostate
      examination was 3.7, and odds ratio to detect prostate cancer by repeat biopsies
      was 4.7. CONCLUSIONS: Repeat ultrasound-guided laterally directed sextant
      prostate biopsies reveal more cases of prostate cancer as compared to the first
      prostate biopsy. The majority of prostate cancer cases (93.3%) are detected by
      the first and second laterally directed sextant prostate biopsies. After the
      first negative prostate biopsy, we recommend to repeat prostate biopsy in high
      risk patients.

PMID- 18084141
TI  - The role of D-dimer in the diagnosis of strangulated small-bowel obstruction.
AB  - BACKGROUND: Various diagnostic utilities have been used in the diagnosis of
      strangulated obstruction. Despite this, there is no simple and reliable marker
      for it, and diagnosis in most cases is based on clinical, laboratory, and
      radiological investigations. The purpose of the present study was to assess D
      dimer value in the diagnosis of strangulated obstruction. METHODS: A prospective
      study of 53 patients with small-bowel obstruction was conducted. Strangulated
      obstruction was present in 15 (28.3%) patients. Eight (53%) had intestinal
      necrosis, while 7 (47%) reversible ischemia. The blood samples were taken and
      analyzed with NycoCard Reader method with monoclonal antibodies specific for D
      dimer neoantigens. RESULTS: In the presence of intestinal necrosis, there was a
      higher D-dimer level found than in the cases with reversible ischemia or simple
      small-bowel obstruction, although this difference did not reach statistically
      significant level. The D-dimer test had a sensitivity of 60%, specificity of 68%,
      positive predictive value of 43%, and negative predictive value of 81% in
      diagnosing strangulated obstruction. CONCLUSION: In present series, D-dimer test
      was neither sensitive nor specific in diagnosing strangulation.

PMID- 18084142
TI  - Long-term results of incisional hernia treatment.
AB  - Ventral hernia is a common problem in general surgery practice. Incisional hernia
      can develop in 15-25% of patients after abdominal surgery. The aim of this study
      was to compare two different methods of incisional hernia surgery. MATERIALS AND
      METHODS: A retrospective analysis of database of surgery department from 1997 to
      2000 was performed. All patients were divided into two groups. The first group
      patients were operated using open suture repair (keel technique); the second
      group patients--using open mesh repair (onlay technique). Long-term follow-up was
      done by a mail questionnaire. A special questionnaire was sent to all patients.
      Postoperative evaluation included pain and discomfort in the abdomen, physical
      activity, and recurrence rate after operation. Statistical evaluation was
      conduced using descriptive analysis: the unpaired Student t test to compare
      parametric criterions between two study groups, Mann-Whitney U test to compare
      the unpaired nonparametric criterions between two study groups, and chi2 test to
      investigate nonparametric criterions between these groups. RESULTS: A total of
      202 patients (51 males, 151 females) with incisional hernia were operated during
      1997-2000. One hundred seventy-one patients were in the keel technique group, and
      31 patients in the onlay technique group. There were no significantly differences
      in age and sex between these groups. The hospitalization time was significantly
      longer in the open mesh repair group. The postoperative complication (wound
      seroma and suppuration) rate was significantly higher in the onlay technique
      group. One hundred sixty-one patients (79.7%) answered the questionnaire (133 in
      the keel technique group, 28 the in onlay technique group). The patients' return
      to physical activity after surgery was significantly longer in the keel technique
      group. Forty-one patients (31%) had hernia recurrence in the keel technique group
      and 3 patients (11%) in the onlay technique group (P<0.05). There were no
      postoperative deaths in both groups. CONCLUSIONS: The rates of postoperative
      therapeutic complications and hernia recurrence are significantly lower after
      open mesh repair surgery. Return to normal physical activity after surgery is
      significantly longer after open suture repair surgery.

PMID- 18084143
TI  - Predictive value of scoring system in severe pediatric head injury.
AB  - OBJECTIVES: To determine the threshold values of Pediatric Index of Mortality 2
      (PIM 2) score, Pediatric Trauma Score (PTS), and Glasgow Coma Scale (GCS) score
      for mortality in children after severe head injury and to evaluate changes in
      outcomes of children after severe head injury on discharge and after 6 months.
      MATERIAL AND METHODS: All children with severe head injury admitted to the
      Pediatric Intensive Care Unit of Kaunas University of Medicine Hospital,
      Lithuania, from January 2004 to June 2006 were prospectively included in the
      study. The severity of head injury was categorized according to the GCS score <
      or =8. As initial assessment tools, the PTS, postresuscitation GCS, and PIM 2
      scores were calculated for each patient. Outcome was assessed according to
      Glasgow Outcome Scale on discharge and after 6 months. RESULTS: The study
      population consisted of 59 children with severe head injury. The group consisted
      of 37 (62.7%) boys and 22 (37.3%) girls; the mean age was 10.6+/-6.02. The mean
      GCS, PTS, and PIM 2 scores were 5.9+/-1.8, 4.8+/-2.7, and 14.0+/-19.5,
      respectively. In terms of overall outcome, 46 (78.0%) patients survived and 13
      (22.0%) died. All three scales appeared to be significant predictors of death.
      Threshold values for which potential mortality in children after severe head
      injury increased were 10.75 for PIM 2, 3 for PTS and 5 for GCS. PIM 2 score
      provided the best discrimination between survivors and nonsurvivors. CONCLUSIONS:
      The threshold values for mortality in children after severe head trauma were PIM
      2> or =10.75%, PTS< or =3 and GCS< or =5, and these values were significant risk
      factors of death in severely head injured children. The changes in outcome for
      survivals on discharge and after 6 months were statistically significant.

PMID- 18084144
TI  - Prevalence of erectile dysfunction among hypertensive and nonhypertensive Qatari
      men.
AB  - OBJECTIVES: The aim of this study was to investigate the prevalence of erectile
      dysfunction, its severity, and other sexual function domains in hypertensive and
      normotensive Qatari's men and to estimate the association between hypertension
      and predictors of erectile dysfunction. MATERIAL AND METHODS: A matched case
      control study was conducted at the primary health care clinics during a period
      from May to October 2006. Four hundred twenty-five hypertensive patients and 425
      age-matched normotensive attendants of primary health care clinics, aged 30-75
      years, were approached for the study. Of them, 296 hypertensive participants
      (74%) and 298 normotensive men (70.1%) gave their consent to participate in it.
      The mean age of the hypertensive participants was 54.8+/-11.5 years as compared
      to nonhypertensive participants with a mean age of 54.5+/-12.1 years. Face-to
      face interviews were based on a questionnaire that included variables on age,
      sociodemographic status, educational level, occupation, cigarette smoking, and
      blood pressure. Hypertension was defined as mild for systolic blood pressure
      (SBP) 120-139 mmHg and diastolic blood pressure (DBP) 80-89 mmHg; moderate for
      SBP 140-159 mmHg and DBP 90-99 mmHg; and severe for SBP >160 mmHg and DBP >100
      mmHg. All patients completed a detailed questionnaire addressing their general
      medical history, with special emphasis on hypertension (i.e., duration of
      hypertension, type of treatment, and presence of any complications). Sexual
      function was evaluated with the International Index of Erectile Function (IIEF).
      RESULTS: Of the 296 hypertensive patients, 196 participants reported erectile
      dysfunction (66.2%), while among the 298 nonhypertensive participants, only 71
      had erectile dysfunction (23.8%). Of the hypertensive participants studied, 25%
      had severe, 29.1% had moderate, and 12.1% had mild erectile dysfunction. The
      percentages of various sexual activity domains were highly significant and at
      higher risk among hypertensive patients than normotensive men (P<0.001).
      Frequency and severity of erectile dysfunction increased with advancing age.
      CONCLUSIONS: Our results have shown that the prevalence of erectile dysfunction
      was significantly higher in Qatari hypertensive men than in normotensive men.
      Age, level of education, diabetes mellitus, occupation, and duration of
      hypertension were considered statistically significant predictors of erectile
      dysfunction. Erectile dysfunction was more common in hypertensive individuals
      receiving antihypertensive treatment.

PMID- 18084145
TI  - [Selective apheresis of low-density lipoproteins in a child].
AB  - The case of rear complicated homozygous hypercholesterolemia treated by a direct
      adsorption of lipoprotein apheresis procedure is presented in this article. In
      total, 30 sessions of direct adsorption of lipoprotein apheresis were performed
      on a 14-16-year-old patient from June 2004 to December 2006. Blood flow rate was
      30-70 mL/min. Central and ulnar veins were punctured. Lipid levels were measured
      before and after lipid apheresis during each session throughout the study period.
      The mean decrease in total cholesterol level was 26.4-71.2% compared to baseline,
      low-density lipoprotein cholesterol--31.9-72.2%, lipoprotein (a)--56.6-90.9%,
      apolipoprotein B--26.4-60.0%. Clinical procedures were completely uneventful. The
      last 26 sessions were performed in a day unit.

PMID- 18084146
TI  - Conservative treatment of cervical pregnancy with selective unilateral uterine
      artery embolization.
AB  - BACKGROUND: Cervical pregnancy is a rare form of ectopic pregnancy, and the most
      effective method of its treatment is still under investigation. We would like to
      call attention to selective uterine artery embolization as an effective modern
      treatment method. CASE: A patient with suspected cervical pregnancy and 7-week
      amenorrhea was admitted to the hospital after unsuccessful use of emergency
      contraception. Transvaginal ultrasound showed gestational sack located 11 mm from
      the external cervical os. Crown-rump length was 11.2 cm, and the fetal heartbeat
      was present. The level of serum chorionic gonadotropin was 31,930 U/L. Treatment
      with systemic methotrexate was unsuccessful, and unilateral uterine artery
      embolization was performed followed by dilatation and curettage of the cervical
      canal. Three days after the procedure, sonographic examination showed contracted
      cervical canal. After a period of two months, normal uterine artery flow was
      registered by Doppler ultrasonography on both sides. CONCLUSION: Uterine artery
      embolization in case of cervical pregnancy reduces the risk of bleeding and can
      be the method of choice when treatment with methotrexate fails. Unilateral
      embolization is effective when angiography shows unequal disposition of the
      arterial connections supplying the embryo.

PMID- 18084147
TI  - [Staphylococcus aureus prevalence among preschool- and school-aged pupils].
AB  - OBJECT: To determine the prevalence and incidence of Staphylococcus aureus
      strains among preschool- and school-aged pupils and susceptibility of these
      strains to antimicrobial materials. MATERIAL AND METHODS: A study of 243
      preschool- and 300 school-aged pupils was conducted during 2003-2004.
      Identification of Staphylococcus aureus was made with plasmacoagulase and DNase
      tests. The resistance of Staphylococcus aureus to antibiotics, beta-lactamase
      activity, phagotypes, and phage groups were determined. The isolated
      Staphylococcus aureus strains were tested for resistance to methicillin by
      performing disc diffusion method using commercial discs (Oxoid) (methicillin 5
      microg per disk and oxacillin 1 microg per disk). RESULTS: A total of 292 (53.8%)
      Staphylococcus aureus strains were isolated and identified (113 (46.5%) from
      preschool- and 179 (59.7%) from school-aged pupils). The prevalence of
      Staphylococcus aureus strains among preschool-aged pupils varied from 46.5% to
      47%. It increased to 59.0% (P>0.05) among schoolchildren aged from 11 to 15 years
      and to 73.0% (P<0.001) among schoolchildren aged from 16 to 19 years. Six
      methicillin-resistant Staphylococcus aureus strains were isolated: two (1.8%) of
      them were from preschool-aged and four (2.2%) from school-aged pupils. The
      prevalence of Staphylococcus aureus strains with beta-lactamase activity
      increased from 70.7 to 76.6% in preschool-aged pupils, and it varied from 72.0 to
      79.0% in school-aged pupils (P>0.05). Staphylococcus aureus strains of phage
      group II (32.2-43.4%) were prevailing; nontypable Staphylococcus aureus strains
      made up 19.2-33.6%. CONCLUSIONS: The prevalence of Staphylococcus aureus among
      preschool-aged children is 41.7 to 48.8%, and it increases among 9th-12th-grade
      pupils (73.0%, P<0.001). Some Staphylococcus aureus strains (2.1%) were resistant
      to methicillin. Staphylococcus aureus strains of phage group II (39.0%, P<0.05)
      are most prevalent among preschool- and school-aged pupils. Pupils were colonized
      with methicillin-resistant Staphylococcus aureus strains belonging to phage group
      III phagotype 83A and 77.

PMID- 18084148
TI  - [Lithuanian version of the Nursing Outcomes Classification Use Survey:
      development and psychometric evaluation].
AB  - Cross-cultural tests and research instruments are broadly used to adapt
      questionnaires developed in different countries and cultures. The Nursing
      Outcomes Classification (NOC)--a comprehensive, standardized classification of
      patient outcomes--can be used to evaluate the results of nursing interventions.
      OBJECTIVE: To develop and test psychometrically the Lithuanian version of the
      Nursing Outcomes Classification Use Survey. MATERIAL AND METHODS: A Lithuanian
      version of the Nursing Outcomes Classification Use Survey was developed following
      traditional methodological procedures of research instrument translation and
      adaptation. The newly developed instrument was tested with a sample of 70 staff
      nurses from nursing and supportive care hospitals. The content and practical
      feasibility of the Lithuanian version of NOC was measured for its reliability and
      validity. Psychometric analysis was conducted with the statistical package SPSS
      13.0 for Windows. Results revealed a successful translation of NOC from English
      to Lithuanian with validity and acceptability of a shortened Lithuanian version
      (244 items instead of the original 330 items). Satisfactory internal consistency
      (Cronbach alpha >0.80 in 18 classes and in 6 classes out of 28 Cronbach alpha
      between 0.70 and 0.80) was defined, and stability in time was very good with a 7
      day break between repeated translations (Spearman-Brown coefficient for the whole
      instrument was 0.806, ranging from 0.707 to 0.970). The majority of items in the
      Lithuanian version correlated with measurement class (correlation coefficients
      >0.40). CONCLUSIONS: The Lithuanian version of Nursing Outcomes Classification
      Use Survey is a reliable, valid, and applicable to outcome identification in
      clinical practice and nursing research. Future research and further evaluation of
      the newly developed Lithuanian version of NOC is suggested.

PMID- 18084149
TI  - [The need of the elderly for nursing and social services in the community of
      Kaunas district].
AB  - The aim of this study was to evaluate the need of the elderly for outpatient
      nursing and social services in Kaunas district. MATERIAL AND METHODS: The object
      of the study was elderly people (aged 65 years and more) living in Kaunas
      district. A questionnaire was used for interviewing. The sample was randomly
      selected from the lists of people registered at the primary health care centers
      (including outpatient departments and medical aid centers). A total of 390
      inhabitants were investigated who represent all the elderly of Kaunas district.
      The independence of the respondents was evaluated by the standard tests (the
      Barthel Index and Mini-Mental State Examination). RESULTS: The respondents
      reported that 71.3% of them needed nursing and 58.2% social services. The need
      for the services was higher in older age group. The rural elderly reported higher
      need for social services (64.3%) than the urban elderly (49.6%). Less than half
      (45.9%) of respondents referred having problems visiting the general
      practitioner. Majority of the respondents (86.4%) pointed out that those who took
      care of them had no special medical training. Totally or almost totally dependent
      respondents (groups by Barthel Index) needed social (88.0%) and nursing (96.0%)
      services. Majority of respondents (79.2%) preferred to be cared at home.
      CONCLUSIONS: More than half of the elderly needed both nursing and social
      services. The need for social services differently from nursing services was
      influenced by the living place of the respondents; the rural elderly needed
      services more than the urban elderly.

PMID- 18084150
TI  - [Ischemic cardiomyopathy: possibilities of surgical treatment].
AB  - The high morbidity and mortality in patients with serious heart failure is a
      therapeutic challenge for current medicine. The leading cause of left ventricular
      dysfunction remains ischemic heart disease. Coronary artery bypass surgery is a
      treatment of choice in moderate-to-severe ischemic cardiomyopathy. The scarcity
      of completed prospective randomized clinical trials and high surgical risks
      create significant uncertainty concerning the optimal current treatment strategy.
      The role of imaging techniques of assessment for myocardial viability based on
      current guidelines may be very important in clinical decision-making. Present
      paper reviews some of the relevant literature concerning surgical treatment of
      ischemic cardiomyopathy and current evidence-based recommendations on this method
      of treatment. In advanced heart failure, coronary revascularization alone is an
      insufficient treatment modality. In the presence of moderate-to-severe ischemic
      mitral regurgitation, mitral valve repair or replacement should be considered at
      coronary artery bypass grafting surgery. One of the most common mechanisms of
      ischemic mitral regurgitation is Carpentier's type IIIb dysfunction, in which an
      undersized mitral anuloplasty might be helpful. Surgery of left ventricular shape
      and volume restoration leads to improvement of left ventricular function in
      patients with ischemic cardiomyopathy. When the results from three ongoing
      prospective randomized studies--the Surgical Treatment for Ischemic Heart Disease
      trial, Heart Failure Revascularization trial, the PET and Recovery Following
      Revascularization-2 trial--determining outcome of revascularization versus
      medical therapy are available, clinicians will have reliable data for making
      decisions concerning the optimum treatment strategy. At present, the choice of
      management still remains based on the data obtained from available retrospective
      trials or the state of art in the field.

PMID- 18084152
TI  - Two amlodipine/ARB combinations for hypertension.

PMID- 18084153
TI  - Extended-release cyclobenzaprine (Amrix).

PMID- 18084154
TI  - Temsirolimus (Torisel) for advanced renal cell carcinoma.

PMID- 18084156
TI  - Fifty years of radioimmunoassay.

PMID- 18084157
TI  - Phenotypic features of 46, XX females with StAR protein mutations.
AB  - OBJECTIVE: To understand the basis of the phenotypic variations of 46, XX girls
      with mutations in the gene for Steroidogenic Acute Regulatory (StAR) Protein. The
      patients with mutation in both the alleles of the StAR gene result in deficiency
      of all the steroidal hormones and severe adrenal insufficiency. The majority of
      the 46, XX females spontaneously undergo puberty but the underlying defect
      ultimately leads to the development of ovarian cysts and premature menopause. The
      mechanism of the lesion in the ovary remains to be understood completely. DESIGN:
      We compiled the description of the clinical information and biochemical data of
      patients with StAR mutation from published manuscripts. These articles were
      collected from the NCBI website (www.pubmed.org) and from the subsequent
      reference searches of retrieved articles. The data of the 46,XX patients with
      proven StAR mutation were included for the review. RESULTS: The majority of StAR
      46,XX females developed irregular menses and ovarian cysts. The ovarian cyst
      enlargement progressively led to torsion and presented as a life-threatening
      emergency. The fertility of 46,XX StAR patients is severely compromised as
      ultimately premature menopause ensued. CONCLUSIONS: Early hormonal replacement is
      warranted to prevent the progressive ovarian cyst formation. Newer techniques to
      preserve the fertility of these patients can be implied early in the pubertal
      developmental process if patients desire pregnancy.

PMID- 18084158
TI  - Endocrine complications in patients with Thalassaemia Major.
AB  - Patients with multi-transfused thalassaemia major may develop severe endocrine
      complications due to iron overload. The anterior pituitary is particularly
      sensitive to iron overload which disrupts hormonal secretion resulting in
      hypogonadism, short stature , acquired hypothyroidism and hypoparathyroidism.
      Glucose intolerance and diabetes mellitus are also common in thalassaemic
      patients. The severity of the clinical manifestation and laboratory findings in
      thalassaemia largely depends on the genotype; thus homozygotes or compound
      heterozygotes for the mutations beta0 or beta+ depend for life on frequent
      transfusions. A multicenter study in Cyprus including 435 patients showed
      hypogonadotrophic hypogonadism in 32.5%, short stature in 35%, acquired
      hypothyroidism in 5.9%, hypoparathyroidism in 1.2% and diabetes mellitus in 9.4%.
      A slowing down of growth velocity and a reduced or absent pubertal growth spurt
      is observed in early adolescence leading to short adult height. Delayed or absent
      puberty and hypogonadism may result in fertility problems which affect enormously
      the life of thalassemics. Glucose intolerance in adolescence and diabetes
      mellitus later in life are also frequent complications mainly due to iron
      overload, chronic liver disease and genetic predisposition. Primary
      hypothyroidism and hypoparathyroidsm usually appear in the second decade of life;
      are related to iron overload and may be reversible at an early stage by intensive
      chelation. Osteopenia and osteoporosis due to a complicated pathogenesis
      represent prominent causes of morbidity in young adults of both genders with
      thalassaemia. Early recognition and prevention of the endocrine complications, by
      early and regular chelation therapy, is mandatory for the improvement of the
      quality of life and psychological outcome of these patients.

PMID- 18084159
TI  - Therapeutic approach to childhood hypercholesterolemia.
AB  - Hypercholesterolemia is associated with increased risk of premature
      cardiovascular disease in adults, while early atherosclerotic lesions (reversible
      fatty streaks and non reversible fibrous plaques) are also associated with
      cardiovascular risk factors including low density lipoprotein-cholesterol (LDL
      C). Although LDL-C is a risk factor that should be addressed in high risk
      children such as those with familial hypercholesterolemia, it is unclear, at
      present, whether there is a certain plasma LDL-C level that would call for an
      intervention regardless of the etiology of elevated LDL-C. Therefore, at present,
      screening the entire population to identify subjects with hypercholesterolemia is
      not justified. The aims of this review are to familiarize the reader with
      inherited diseases that are associated with elevated LDL-C and discuss the
      management of children with elevated LDL-C.

PMID- 18084160
TI  - Exercise and type 1 diabetes mellitus in youth; review and recommendations.
AB  - Regular physical activity has been one of the cornerstones of type 1 diabetes
      mellitus (T1DM) therapy for decades. The benefits attributed to regular physical
      activity include increased sense of well being, quality of life, improved body
      composition, improved blood pressure and more. The beneficial effect in
      individuals with T1DM includes decreased risk of diabetes-related complications
      and mortality. In view of the recent recommendations for physical activity in
      healthy youth, advocating daily participation in 60 minutes of moderate to
      vigorous physical activity, we review the recent literature regarding physical
      activity in the context of youth with T1DM. We discuss its physiological and
      metabolic effects in youth with T1DM, its health promoting benefits and
      challenges that exercise poses in these individuals.

PMID- 18084161
TI  - Continuous insulin infusion (CSII) or modern type of multiple daily injections
      (MDI) in diabetic children and adolescents a critical review on a controversial
      issue.
AB  - OBJECTIVE: There is a common opinion that CSII is superior to MDI. CSII offers
      the most physiological insulin substitution. METHOD: Review of recent
      publications (Cochrane criteria), on modern multiple daily injections (MDI) based
      on insulin analogues, modern self-control and education. RESULTS: There is a lack
      of randomised controlled studies comparing CSII with modern MDI in children and
      adolescents. In some studies CSII seems to give a slight decrease of HbA1c, a
      slightly better quality of life, perhaps less hypoglycemia. However, serious
      hypoglycemia, sometimes fatal, occurs, DKA seems to increase, weight gain and
      local infections at injection sites may occur and CSII is more expensive than
      MDI. CONCLUSION: CSII is a useful tool. It is reasonable to use it when there are
      appropriate indications. CSII does not solve all problems but has to be combined
      with other important parts of diabetes treatment.

PMID- 18084162
TI  - Examination of the skin in patients with gynecomastia.

PMID- 18084163
TI  - Meeting Report:The 7th ESPE Growth Plate Working Group Symposium - EUROGROP June
      27th 2007, Helsinki, Finland.
AB  - Longitudinal bone growth occurs within the epiphyseal growth plate, a highly
      organized biological structure located at the distal ends of the long bones, via
      endochondral bone formation. This developmentally regulated process is finely
      tuned through the interaction of circulating systemic hormones and locally
      produced peptide growth factors, the net result of which is to trigger changes in
      gene expression by growth plate chondrocytes. These molecular events lead to
      carefully orchestrated alterations in chondrocyte size, extracellular matrix
      components, secreted enzymes, growth factors and receptor expression. These
      events finally result in calcification of the matrix, chondrocyte death, vascular
      invasion and the completion of endochondral bone formation. Although the past
      several years have seen important progress in the identification of numerous
      important factors, which, in a complex and integrated network, control
      longitudinal bone growth, many of the signaling pathways and their interactions
      in the growth plate remain poorly understood. The ESPE Growth Plate Working Group
      (EUROGROP) was established in 2000 with the aim of bringing together both basic
      and clinical European research groups with an interest in the biology and
      pathology of the growth plate. The 7th EUROGROP Symposium was held as an official
      ESPE working group of the 46th ESPE Annual Meeting held in Helsinki, Finland,
      2007. It enabled researchers, coming from all parts of the world to discuss their
      ongoing studies and exchange technical information. The program consisted of
      three lectures and four original papers, all followed by attractive discussions.
      This report summarizes the data presented and provides some comments on each of
      the presentations. ABBREVIATIONS: 11beta-HSD: 11 Beta-Hydroxysteroid
      Dehydrogenase; Agc: Aggrecan; Aln: Alendronate; Asb- 4: Ankyrin Repeat and SOCS
      Box-Containing Protein 4; Atf6: Activating Transcription Factor6; BSP:
      Bisphosphonates; Calca: Calcitonin, Alpha Cdkn2a: Cyclin-Dependent Kinase
      Inhibitor 2A; Col1: Collagen 1; Col2: Collagen 2 Col10: Collagen 10; Dex:
      Dexamethasone; Elk1: Member of ETS Oncogene Family; Esr1: Estrogen Receptor 1
      (Alpha); Fli1: Friend Leukemia Integration 1; Gabp: GA Repeat Binding Protein;
      GC: Glucocorticoids; Ghr: Growth Hormone Receptor; Hif-1alpha: Hypoxia-Inducible
      Factor 1 Alpha; hMSCs: Human Mesenchymal Stem Cells; Igf1: Insulin-Like Growth
      Factor 1; Igfbp1: Insulin-Like Growth Factor Binding Protein 1; Igf1r: Insulin
      Like Growth Factor 1-Receptor; Igf2: Insulin-Like Growth Factor 2; Igf2r: Insulin
      Like Growth Factor 2-Receptor; Nfe2l2: Nuclear Factor, Erythroid Derived 2, Like
      2; Nrf1: Nuclear Respiratory Factor 1; Pam: Pamidronate; Prss11: HtrA Serine
      Peptidase 1; PTU: Propylthiouracil; Pycard: PYD and CARD Domain Containing; Rxrg:
      Retinoid X Receptor Gamma; Tam: Tamoxifen.

PMID- 18084164
TI  - The 9th European congress of endocrinology.

PMID- 18084165
TI  - Hip-fracture type does not affect the functional outcome after acute in-patient
      rehabilitation: a study of 684 elderly women.
AB  - AIM: To investigate differences in the functional outcome between women
      sustaining cervical or trochanteric fractures of the hip. METHODS: We studied 684
      of 736 women admitted consecutively to a rehabilitation hospital in Italy because
      of their first hip fracture. Functional recovery was assessed by using Barthel
      index scores. Fractures were classified as either cervical (n=335) or
      trochanteric (n=349) on the basis of surgical and radiographic findings. RESULTS:
      After acute in-patient rehabilitation, women with trochanteric fracture had a
      significantly lower Barthel index score than women with cervical fracture (median
      values were 85 and 90 respectively, interquartile ranges were 25 and 30
      respectively, P=0.001). Length of stay in the hospital was significantly longer
      in women with trochanteric fractures (median was 37 days vs 36 days;
      interquartile range was 10 days vs 8 days, P=0.018). However, the differences
      between the two groups were no longer significant after adjustment for eight
      variables that affect functional ability in the same population (i.e., age,
      pressure ulcers, cognitive impairment, neurologic impairment, infections during
      the length of stay, bone mineral density, body mass index, and Barthel index
      scores assessed before rehabilitation). Further-more, we found no significant
      differences in the change of Barthel index scores during rehabilitation and in
      Barthel index efficiency (change in the Barthel index score after rehabilitation
      divided by the length of stay in hospital) between the two groups of women.
      CONCLUSIONS: After adjustment for several confounders, we did not show
      significant differences in the functional outcome between women with cervical or
      trochanteric fracture of the hip.

PMID- 18084166
TI  - Rehabilitation of chronic graft versus host disease in children. A clinical
      series.
AB  - The study was aimed at evaluating clinical and functional assessment and results
      obtained following rehabilitative treatment in children affected by chronic graft
      versus host disease (cGVHD) after allogeneic transplantation of hemopoietic stem
      cells (HSCT). From 1999 to 2003 we evaluated 6 children with cGVHD after HSCT
      presenting severe complications and disabilities. Clinical and functional
      assessment was performed prior to rehabilitative treatment (T1), at follow-up at
      6 (T6) and 12 (T12) months after treatment. Each child received a personalized
      rehabilitative treatment program based on the use of neuromotor re-education
      techniques, massotherapy, chest rehabilitation and occupational therapy. Six
      children presented sclerodermoid skin lesions, joint contractures, anchylosis,
      respiratory insufficiency, postural and walking alterations which led to
      reduction in motor performance and autonomy in daily living activity. After 1
      year of rehabilitation treatment, 3 patients showed improvement in motor
      performance, 2 remained stable and 1 patient worsened. Rehabilitative treatment
      associated with pharmacological therapy has proven to be useful in patients
      affected by cGVHD. We believe that cGVHD is a pathology which must be seen by a
      physiatrist as early as possible at onset of first cutaneous signs of cGVHD to
      limit its invalidating evolution.

PMID- 18084167
TI  - Rasch psychometric validation of the Impact on Participation and Autonomy
      questionnaire in people with Parkinson's disease.
AB  - AIM: The aim of this study was to assess the psychometric properties of the
      Impact on Participation and Autonomy (IPA) questionnaire, in its two scales: IPA
      I, perceived limitations in participation and autonomy; IPA-II, perceived
      problems in participation. METHODS: The IPA data underwent Rasch analysis for
      rating scale diagnostics and a reliability and validity study. The work and
      education domain was left out of the analysis due to its low applicability to our
      subjects. A convenience sample of 100 patients with Parkinson's disease (PD) (41
      male, 59 female; mean age 72+/-7 years) were consecutively observed at our
      Rehabilitation Clinic. RESULTS: According to Rasch analysis, two response
      categories of IPA-I were collapsed into one and 1 item (''intimate
      relationship'') was deleted. The remaining 24 items fitted the unidimensional
      construct that the scale was intended to measure. IPA-I demonstrated good
      reliability (person separation = 0.93, item separation = 0.97) and internal
      construct validity. All six IPA-II items proved to belong to the same construct.
      For IPA-II, item separation = 0.97, person separation = 0.71. The targeting and
      spread of item difficulty and the quite low person separation reliability of IPA
      II made it possible only to differentiate people with low vs high level of
      problems in participation. Both scales showed the expected correlation with PD
      specific clinical and quality of life measures. CONCLUSIONS: IPA-I shows promise
      as a tool for measuring participation in people with PD. IPA-II has acceptable
      psychometric characteristics for measuring perceived problems in participation.
      Additional steps to improve their metric properties and further studies in people
      with different kinds of health conditions need to be carried out.

PMID- 18084168
TI  - A new mechanical arm trainer to intensify the upper limb rehabilitation of
      severely affected patients after stroke: design, concept and first case series.
AB  - Description and case series on a new mechanical arm trainer with three degrees of
      freedom (DoF), the REHA-SLIDE (RS), for stroke rehabilitation are presented.
      Similar to a rolling pin, it consists of two handles at either side of a
      connecting rod, the handles are bilaterally moved forward and backward, sideways,
      and rotated, the base plate is inclinable. A computer mouse attached to the rod
      enables playing games offering computer-biofeedback. Two patients, 6 and 5 weeks
      after a first-time supratentorial stroke, suffering from a flaccid non-functional
      upper extremity have been studied. Interventions performed were additional 30 min
      of RS-training every workday for 6 weeks; one session included 400 repetitions
      evenly distributed between the forward backward movement and drawing a circle
      clock- and counter clockwise. Afterwards the patients could play games. Upper
      extremity portion of the Fugl-Meyer Motor Assessment Score (FM, 0-66), and muscle
      strength by a Medical Research Council (MRC) sum score (0-45), the FM assessment
      was blinded. In the 2 patients, the FM (0-66) improved from 7 to 37, and from 17
      to 43, their initial (terminal) MRC sum scores were 6 (36) and 13 (31). With the
      REHA-Slide (RS), severely affected patients practiced a bilateral 3 DoF movement.
      No conclusions can be drawn so far and a controlled clinical study must be the
      next step.

PMID- 18084169
TI  - Frozen shoulder development secondary to proximal humerus fracture and
      supraspinatus tendon tear following electrical injury.
AB  - Musculoskeletal injury incidence occurring as a result of low voltage electrical
      accidents is extremely rare. In the present paper, we report 2 cases of low
      voltage electrical injuries with frozen shoulder development secondary to
      proximal humerus fracture and supraspinatus tendon tear. Magnetic resonance
      imaging, taken due to persistence of shoulder pain and reduction of shoulder
      joint mobility in cases monitored because of proximal humerus fracture associated
      with electrical injury, revealed a tear of supraspinatus tendon. Moreover, frozen
      shoulder status was clinically established in both of the cases. The cases were
      treated with an appropriate physical therapy and rehabilitation program.
      Supraspinatus tendon tears accompanying proximal humerus fractures should not be
      overlooked in low voltage electrical injuries and development of frozen shoulder
      should be avoided by applying the proper physical therapy and rehabilitation
      program.

PMID- 18084170
TI  - Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary
      disease. A Cochrane systematic review.
AB  - BACKGROUND: The widespread application of pulmonary rehabilitation in chronic
      obstructive pulmonary disease (COPD) should be preceded by demonstrable
      improvements in function attributable to the programs. OBJECTIVES: To determine
      the impact of rehabilitation on health-related quality of life (QoL) and exercise
      capacity in patients with COPD. METHODS: We identified randomized controlled
      trials (RCTs) from the Cochrane Airways Group Specialised Register. We selected
      RCTs of rehabilitation in patients with COPD in which quality of life (QoL)
      and/or exercise capacity were measured. Rehabilitation was defined as exercise
      training for at least 4 weeks with or without education and/or psychological
      support. Control groups received conventional community care without
      rehabilitation. RESULTS: A total of 31 RCTs met the inclusion criteria. We found
      statistically significant improvements for all the outcomes. In 4 important
      domains of QoL (Chronic Respiratory Questionnaire scores for Dyspnea, Fatigue,
      Emotional function and Mastery), the effect was larger than the minimal
      clinically important difference. For exercise capacity, the effect was small and
      slightly below the threshold of clinical significance for the six-minute walking
      distance (WMD: 48 m; 95% CI: 32 to 65; n = 16 trials). CONCLUSIONS:
      Rehabilitation relieves dyspnea and fatigue, improves emotional function and
      enhances patients' control over their condition. These improvements are
      moderately large and clinically significant. Rehabilitation forms an important
      component of the management of COPD.

PMID- 18084172
TI  - The effect of cardiac rehabilitation on quality of life, anxiety and depression
      in patients with congestive heart failure. A randomized controlled trial, short
      term results.
AB  - AIM: One of the major treatment goals in congestive heart failure (CHF) is to
      preserve the functional level of the patient and to improve psychosocial factors.
      For these purposes, exercise training is recommended for the management of CHF.
      With this background, the aim of this study is to investigate the effects of
      aerobic exercise on quality of life, depression and anxiety levels in a Turkish
      patient population with CHF. METHODS: Sixty patients with CHF in stage II-III
      according to NYHA were included. Patients were randomly assigned either to a
      cardiac rehabilitation group or to a control group. Twenty-seven patients were
      allocated to a weekly aerobic walking program on treadmill, thrice a week for 8
      weeks, and 26 patients did not receive any exercise training. Both groups were
      assessed by an ergospirometric exercise test, Hacettepe Quality of Life
      Questionnaire (HQoL), Beck Depression Inventory (BDI), Spielberger Trait Anxiety
      Inventory (STAI) at baseline and at the end. RESULTS: Forty-four patients
      (treatment group: 23) completed the study. In the treatment group, significant
      increases in peak oxygen consumption, exercise time and metabolic equivalents
      (MET) levels were attained (P=0.001, P=0.001, P=0.003, respectively). Significant
      decreases in BDI (P=0.004) and STAI subgroups (P=0.049, P=0.023, respectively)
      were observed, whereas there was no change in HQoL scores. In the control group,
      there was no difference between baseline and 8th week evaluation in all
      parameters. CONCLUSIONS: Patients with CHF tolerated aerobic exercise programs
      well. This resulted with improvement in both physical and psychologic wellbeing,
      but not in quality of life in the short term.

PMID- 18084173
TI  - Can we improve gait skills in chronic hemiplegics? A randomised control trial
      with gait trainer.
AB  - AIM: Partial body weight support (PBWS) is an accepted treatment for hemiplegic
      patients. The aim of this study is to compare the efficiency of gait trainer with
      conventional treatment on the gait management after stroke. METHODS: Forty
      chronic post-stroke hemiplegics were part of a prospective research. Inclusion
      criteria were: first ever stroke in a chronic stage with stabilised motor
      deficits; age >18 and <80 years; cognitive and communication skills to understand
      the treatment; absence of cardiac, psychological and orthopedic
      contraindications. Patients were randomised into two groups: the control group
      (CG) that used the Bobath method in 40 minutes sessions, 5 times a week, for 5
      weeks, and the experimental group (EG) that used the gait trainer, for the same
      period of time and frequency. Assessment tools: Motricity Index (MI); Toulouse
      Motor Scale (TMS); modified Ashworth Spasticity Scale (mASS); Berg Balance Scale
      (BBS); Rivermead Mobility Index (RMI); Fugl-Meyer Stroke Scale (F-MSS);
      Functional Ambulation Category (FAC); Barthel Index (BI); 10 meters, time up and
      go (TUG), 6 minutes, and step tests. EG and CG did the assessments before
      treatment (T(0)), right after treatment (T(1)), and on follow-up, 3 months later
      (T(2)). RESULTS: CG and EG were homogenous in all the variables at T(0). CG and
      EG showed improvement in almost all the assessment scales after treatment,
      although only some with relevant differences. EG showed statistically relevant
      improvement on T(1) and on T(2) in several of the assessment tools, whereas CG
      only showed statistically significant improvement after T(1) and only in some of
      the assessment tools. CONCLUSIONS: Both groups of chronic hemiplegic patients
      improved after either PBWS with gait trainer or Bobath treatment. Only subjects
      undergoing PBWS with gait trainer maintained functional gain after 3 months.

PMID- 18084174
TI  - Do bulbar-onset amyotrophic lateral sclerosis patients have an earlier
      respiratory involvement than spinal-onset amyotrophic lateral sclerosis patients?
AB  - AIM: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative
      disease involving limbs and bulbar muscles. The major cause of death in these
      patients is respiratory insufficiency. However, bulbar-onset ALS patients have a
      shorter survival than those with spinal-onset. It is not established if this
      difference is related to an earlier respiratory dysfunction in bulbar-onset
      patients. The aim of the present study was to determine if bulbar-onset patients
      have an earlier respiratory impairment as compared with the spinal-onset ones.
      METHODS: From the population of ALS patients followed in our centre, we studied
      82 patients (45 spinal-onset and 37 bulbar-onset, group 1 and 2 respectively),
      all evaluated between 6-18 months after disease onset. We investigated forced
      vital capacity, maximal inspiratory (PI max) and expiratory (PE max) pressures,
      mouth occlusion pressure at 100 ms after inspiration, arterial blood gases,
      percutaneous nocturnal oxymetry, phrenic nerve conduction, needle
      electromyography (EMG) of the right diaphragm and right internal intercostals
      muscles and functional ALS scale (ALS-FRS). RESULTS: No statistical difference
      was found for gender and disease duration between both groups, but bulbar-onset
      patients were older. PI max and PE max were statistically lower (P<0.001 and
      P<0.006, respectively) in group 2. However, no correlation was found between
      bulbar ALS-FRS subscore and PI max or PE max. CONCLUSIONS: Our results support
      that PI max and PE max are sensitive measurements of respiratory dysfunction in
      bulbar patients. Probably, this finding cannot be solely explained by the oro
      facial weakness of bulbar-patients. We speculate that respiratory accessory
      muscles weakness can contribute for this observation.

PMID- 18084175
TI  - Functional assessment in rehabilitation: conceptual framework, goals and
      instruments.

PMID- 18084176
TI  - Functional assessment in rehabilitative medicine: principles and methods.
AB  - In rehabilitative medicine, functional assessment means a decision process that
      results from the interaction between classifications (for example, diagnostic)
      and measures, and that aims to recognize, anticipate or modify the interaction
      between the disabled person and his environment. In this context, the measure is
      the intersection of a person along the conceptual gradient and continuum ''from
      less to more'' attributed to variability in the ''total person,'' such as
      independence, pain, cognitive capacity, or fatigability. The principal instrument
      is the additive questionnaire (functional scale). This consists of various items
      believed to represent a common variable. These kinds of variables are observable
      only partially across various aspects of the whole person, and are not completely
      predictable. Their measure, consequently, can only be derived from an estimated
      statistic. The additive questionnaire is the principal measurement instrument.
      Several items all representing the same variable receive scores whose sum is
      assumed to be proportional to the quantity of the underlying variable. For
      various reasons the sum of the scores does not represent a true linear and
      continuous measure like those seen in chemistry and physics. Recently developed
      methods, in particular Rasch analysis, can extract true measures from raw scores.
      Thanks to better measurement of variability in persons within rehabilitative
      medicine, functional assessment can become increasingly more valid and
      informative.

PMID- 18084177
TI  - Functional assessment in physiotherapy. A literature review.
AB  - The present literature review on functional assessment in physiotherapy was
      carried out for the following reasons: 1) to identify the functional instruments
      used in the field of physiotherapy that were supported by published evidence of
      their psychometric qualities; 2) to investigate how these instruments relate to
      the International Classification of Functioning, Disability and Health (ICF); and
      3) to investigate the use of functional instruments in the financing of
      physiotherapy. A search of Medline from 1990 to December 2005, in the domains of
      functional evaluation, psychometric qualities, functional classification, and
      health policy in relation to physiotherapy resulted in a list of 1,567 studies.
      Two reviewers examined the resulting references on the basis of their title and
      abstract, in order to select the studies that presented data on the psychometric
      qualities of functional evaluation tests, leading to a final selection of 44 such
      studies. A selection of functional tests was identified in four major diagnostic
      groups treated in community physiotherapy: musculoskeletal disorders (including
      lower back pain), stroke, the elderly, and traumatic brain injuries. The
      functional tests authors identified essentially cover the body and activities
      dimension of the ICF. The selected tests could be used as a basis for the
      standardisation of functional evaluation of the major diagnostic groups treated
      in community physiotherapy. This means that standards are available for reporting
      and following the evolution of patients both longitudinally and transversally.
      Nevertheless, in the current literature review no attempt at using functional
      outcomes as a rationale for financing physiotherapy could be found to date.

PMID- 18084178
TI  - Untangling function: measuring the severity, type and meaning of disabilities.
AB  - In this commentary, we argue that the current biomedical and psychosocial models
      of illness that form the basis of medicine are insufficient to describe this
      interface. We offer a biopsycho-ecological model of illness and disability
      referred to as health environmental integration (HEI) as a framework intended to
      encourage a more complete understanding of disability as arising at the interface
      between the person's internal and external worlds. By this model, person-level
      functional abilities as well as the subjective meaning of those functions result
      in part from interactions created by the exchange of energy and information
      between the person and his environment. Three components are essential in
      measuring function: severity of deficit, type of deficit, and meaning. We present
      functional status staging as an approach to measuring severity and type of
      deficit, and recovery preference exploration as a way to measure meaning.
      Rehabilitation medicine can come closer to bridging the gap between biological
      and the subjectively-based aspects of human function, by measuring all three
      concepts.

PMID- 18084179
TI  - Functional assessment in rehabilitation medicine: clinical applications.
AB  - Functional assessments have become a cornerstone of rehabilitation medicine,
      assisting in well-defined aspects such as: quality assurance, continuous quality
      improvement, accountability, cost/benefit analysis, education, and research. In
      the second part of the 20th century, scaling techniques have become an integral
      part of the rehabilitation medicine discipline, and everybody is aware of their
      essential importance. However, even when engaged in a purely scientific
      discussion on the theoretical, mathematical basis of these measurements, a
      fundamental question arises as to what depth of accuracy is it possible to bring
      such measurements into a clinical scenario (or any real scenario). When it comes
      to the integration of all these principles, a balance must be achieved between
      pure theory and clinical applications, making it accessible for the average
      clinician and department routinely running functional evaluations. All these
      considerations are discussed with examples of data management that can be
      performed by systematically collecting data with the help of a computerized
      database where demographic, clinical and functional data is recorded.
      Rehabilitation teams and systems must be aware of function measurement principles
      and applications and determine their position in this regard.

PMID- 18084180
TI  - Functional assessment in rehabilitative medicine.

PMID- 18084181
TI  - Rehabilitation and outcome measurement: where is Rasch analysis going?

PMID- 18084184
TI  - Beyond PubMed. Other free-access biomedical databases.
AB  - This article presents several popular free-access biomedical databases (general,
      genetic, pharmacological, evidence-based oriented, or dealing with health
      technology assessment) from which researchers can select the best tool for the
      purpose and context of a specific research. Some gateways for searching across
      multiple databases that provide a ''one-stop shopping'' point of access are also
      presented.

PMID- 18084182
TI  - Role of stretching in Charcot-Marie-Tooth disease.

PMID- 18084185
TI  - How microorganisms tip the balance between interleukin-12 family members.
AB  - Interleukin-12p70 (IL-12p70) induces T-helper-1-cell responses and IL-23, a
      related cytokine, is the master switch in several T-cell-mediated inflammatory
      disorders. IL-27, another member of the IL-12 family, regulates innate and
      adaptive immune responses. Recently, distinct combinations of transcription
      factors have been shown to regulate the expression of the genes that encode these
      three cytokines. Toll-like receptor ligands, in association with other microbial
      products and endogenous mediators, tip the balance between the expression of IL
      12 family members and thereby may control the outcome of T-cell-mediated
      inflammation. On this basis, we present a novel perspective on the pathogenesis
      and regulation of inflammatory disorders.

PMID- 18084187
TI  - Reining in RNA. Workshop on intracellular RNA localization and localized
      translation.

PMID- 18084188
TI  - Silencing the alarm: insights into the interaction between host and pathogen.
      Conference on Microbial Pathogenesis: Mechanisms of Infectious Disease.

PMID- 18084186
TI  - The Drosophila NURF remodelling and the ATAC histone acetylase complexes
      functionally interact and are required for global chromosome organization.
AB  - Drosophila Gcn5 is the catalytic subunit of the SAGA and ATAC histone acetylase
      complexes. Here, we show that mutations in Gcn5 and the ATAC component Ada2a
      induce a decondensation of the male X chromosome, similar to that induced by
      mutations in the Iswi and Nurf301 subunits of the NURF nucleosome remodelling
      complex. Genetic studies as well as transcript profiling analysis indicate that
      ATAC and NURF regulate overlapping sets of target genes during development. In
      addition, we find that Ada2a chromosome binding and histone H4-Lys12 acetylation
      are compromised in Iswi and Nurf301 mutants. Our results strongly suggest that
      NURF is required for ATAC to access the chromatin and to regulate global
      chromosome organization.

PMID- 18084189
TI  - A survey of the workload of dental therapists/hygienist-therapists employed in
      primary care settings.
AB  - AIM: To determine whether dental therapists/hygienist-therapists employed in UK
      primary care settings are currently fulfilling a mainly preventive or therapeutic
      role, and whether the pattern of work they undertake depends upon the specific
      setting in which they are employed. DESIGN: Self-administered postal
      questionnaire including a day-book proforma. RESULTS: Useable day-book proformas
      were received from 209 dental therapists/hygienist-therapists. Their analysis
      indicated that those working in the GDS (when compared with those working in the
      CDS) are predominantly treating adults and being delegated a preventive role
      which could equally be fulfilled by singly-qualified dental hygienists.
      CONCLUSION: This study suggests that primary care dentists working with dental
      therapists/hygienist-therapists are currently utilising only a small range of
      these professionals' skills. Consideration should be given as to whether to (a)
      meet the wishes of dentists by training singly-qualified hygienists, or (b)
      develop a system which encourages dentists to use dental therapists/hygienist
      therapists differently.

PMID- 18084190
TI  - Facets of job satisfaction of dental practitioners working in different
      organisational settings in England.
AB  - INTRODUCTION: Before April 2006, English dentists were either working as an NHS
      general dental service (GDS) practitioner (fee-per-item, no local contractual
      obligations); an NHS personal dental service (PDS) practitioner (block contract
      with the primary care trust (PCT)); a private practitioner (either fee-per-item
      or capitation-based, independent of the PCT); or in a situation where they were
      mixing their NHS work (either under the GDS or PDS arrangements) with private
      work. OBJECTIVES: To a) investigate the extent of the mix of NHS and private work
      in English dentists working in the GDS and PDS, b) to compare global job
      satisfaction, and c) to compare facets of job satisfaction for practitioners
      working in the different organisational settings of PDS practices, GDS practices
      and practices where there is a mix of NHS and private provision. Method A
      questionnaire was sent to 684 practitioners, containing 83 attitudinal statements
      relating to job facets, a global job satisfaction score and questions concerning
      workload. RESULTS: Response rate was 65.2%. More PDS than GDS dentists were found
      to treat the majority of their patients under the NHS. GDS dentists working fully
      in the NHS were least likely to be satisfied with their job, followed by PDS
      practitioners and then GDS dentists working in mixed NHS/private practices.
      Private practitioners were the most satisfied. CONCLUSION: Differences between
      GDS, PDS and private practitioners were found in global job satisfaction and in
      the facets of job satisfaction related to restriction in being able to provide
      quality care, control of work and developing clinical skills.

PMID- 18084191
TI  - Sour sweets: a new type of erosive challenge?
AB  - OBJECTIVE: To assess the erosive potential of a number of commercially available
      sour sweets in the laboratory. METHODS: The erosive potential was assessed by
      measuring the pH, neutralisable acidity and ability to erode permanent and
      deciduous enamel. These parameters were compared to those of an orange juice
      positive control. RESULTS: The pH of the sour sweets ranged from 2.30-3.14 with
      their neutralisable acidity ranging from 9.78-66.9 ml of 0.1M NaOH. The amount of
      permanent enamel removed following one hour immersion in the drinks ranged from
      2.16-10.88 microm and from 1.02-18.34 microm for deciduous enamel. In comparison,
      the orange juice (Tropicana smooth) control had a pH of 3.86, a neutralisable
      acidity of 37.1 ml of 0.1M NaOH and removed 5.23 microm of permanent enamel and
      6.27 microm of deciduous enamel. CONCLUSION: All the sour sweets tested were
      found to be erosive, some more so than orange juice. This information will be of
      use to clinicians when counseling younger patients with tooth surface loss.

PMID- 18084193
TI  - Bite relief.

PMID- 18084194
TI  - The KITS scheme.

PMID- 18084195
TI  - Conflicting advice.

PMID- 18084196
TI  - Biochemical abnormality.

PMID- 18084197
TI  - Shisha confusion.

PMID- 18084199
TI  - Nit-picky comments.

PMID- 18084201
TI  - Open wider.

PMID- 18084202
TI  - Paediatric consent.

PMID- 18084203
TI  - Stopping hair loss with good oral health.

PMID- 18084207
TI  - An evidence-based toolkit for prevention launched.

PMID- 18084208
TI  - Christmas cover artwork offer for BDJ readers.

PMID- 18084212
TI  - A clinical evaluation of the individual repeatability of three commercially
      available colour measuring devices.
AB  - OBJECTIVE: The objective of this study was to undertake a clinical evaluation of
      the individual repeatability of three colour measuring devices. DESIGN: Clinical
      study. Setting Eastman Dental Hospital. METHODS: Under standardised clinical
      conditions, one trained operator using three colour measuring devices (Vita
      Easyshade, X-Rite ShadeVision and Spectroshade Micro) recorded three shade
      measurements (cervical, body and incisal) for each of the upper maxillary
      anterior teeth in 20 participants. This sequence of measurements was repeated for
      each of the shade machines. The output recorded from each sequence included Vita
      classic shades and CIE Lab co-ordinates. Ethical approval was obtained from the
      joint University College London and University College London Hospitals. RESULTS:
      Spectroshade Micro had good agreement Cohen Kappa score (0.80) for repeatability
      of Vita shades and also had 82.7% proportion of complete agreement for Vita
      shades. The proportion of complete agreement for Vita shades for the Easyshade
      and X-Rite ShadeVision machine were 50% and 59% respectively. For CIE Lab co
      ordinates the Spectroshade Micro provided the narrowest range of 'Bland and
      Altman' agreement limits for all the co-ordinates recorded. CONCLUSION: The
      Spectroshade Micro machine provided the most repeatable measurements. Narrower
      limits of agreement indicate greater consistency compared to Easyshade and X-Rite
      ShadeVision.

PMID- 18084213
TI  - Patient preferences for dental clinical attire: a cross-sectional survey in a
      dental hospital.
AB  - AIMS AND OBJECTIVES: This cross sectional descriptive study was designed to
      survey patient opinion towards dental clinical attire, name badges and commonly
      used cross-infection control measures. METHOD: Patients attending a dental
      hospital for a consultation appointment were asked to complete a questionnaire
      accompanied by photographs of models portraying a range of clinical attire. A
      representative sample of patients completed 188 questionnaires over a four week
      period. RESULTS: The study found that the majority of patients felt clinical
      attire was important and that they preferred dental professionals to wear name
      badges. The majority of patients also preferred dentists to use both safety
      glasses and face masks. When asked to indicate which clinical attire was most
      appropriate for a consultant/specialist to wear, the overwhelming opinion was
      that of smart dress accompanied with a white coat. In addition, most respondents
      wished their dentist to wear a traditional white, dental tunic. CONCLUDING
      REMARKS: It is hoped that this study will be informative for the dental team and
      that the results will be taken into consideration when considering appropriate
      clinical attire in accordance with patient opinions.

PMID- 18084214
TI  - The influence of varying maxillary lateral incisor dimensions on perceived smile
      aesthetics.
AB  - OBJECTIVE: The aim of this study was to determine the influence of varying the
      dimensions of the maxillary lateral incisors on perceived smile aesthetics.
      DESIGN: Clinical study. SETTING: Postgraduate dental teaching hospital. METHODS:
      A photograph of a female smile displaying only the lips and teeth was digitally
      altered. First, the width of the maxillary lateral incisors, in proportion to the
      central incisor, was altered at 5% intervals to produce six images (52%, 57%, 62%
      [the 'golden proportion'], 67%, 72% and 77%). In a second group, the length of
      the lateral incisor was altered at 0.5 mm increments to produce five images with
      the lateral incisor 0.5 mm, 1 mm, 1.5 mm, 2 mm and 2.5 mm shorter than the
      adjacent central incisor. The photos were ranked from 'most attractive' to 'least
      attractive' by 41 hypodontia patients, 46 non-hypodontia 'control' patients and
      30 dentists. RESULTS: The 67% followed by the 72% lateral-to-central width
      proportions were the 'most preferred' by all groups. A maxillary lateral incisor
      that is 1-1.5 mm shorter than the central incisor was the 'most popular'
      maxillary lateral incisor length. The very short and very long maxillary lateral
      incisor was consistently perceived as 'least attractive'. CONCLUSION: There is no
      evidence to suggest that the golden proportion should be considered the ideal
      aesthetic standard when creating space for the replacement of missing lateral
      incisors.

PMID- 18084219
TI  - The potential for delegation of clinical care in general dental practice.
AB  - This study describes the proportion and volume of work undertaken in primary
      dental care that could be delegated to hygienists and therapists. METHODS: Data
      on treatment provision, both NHS and private, over one course of treatment for
      850 consecutively attending patients at 17 dental practices, selected to be
      representative of a range of socioeconomic, urban and rural environments, were
      extracted from case records. RESULTS: The 850 patients attended on 2,433
      occasions. Diagnostic examination accounted for 833 (34.2%) visits, while simple,
      intermediate and complex restorative interventions and other complex
      interventions accounted for 500 (20.5%), 361 (14.8%), 365 (15%) and 374 (15.4%)
      visits respectively. The total time required to provide the care was 42,800
      minutes, of which 6,550 (15.3%) were devoted to diagnostic examinations, while
      10,485 (24.5%), 7,935 (18.5%) and 11,790 (27.5%) were taken up with simple,
      intermediate and complex restorative care. Other complex interventions accounted
      for 6,040 (14.2%) minutes. Assuming that dental therapists are permitted to
      undertake simple and intermediate restorative interventions, they could provide
      35.3% of care when number of visits is utilised as the outcome measure, but 43%
      of the clinical time taken to provide care. Delegation of diagnostic and
      treatment planning powers to dental therapists could potentially result in 69.5%
      of visits and 58.3% of clinical time being provided by therapists. CONCLUSION:
      These data imply that a considerable proportion of work in UK general dental
      practice could be delegated to dental hygienists and therapists.

PMID- 18084220
TI  - Smoking, alcohol and drug use among vocational dental practitioners in 2000 and
      2005.
AB  - OBJECTIVE: To estimate the prevalence of tobacco smoking, alcohol and drug use
      among UK vocational dental practitioners (VDPs) in 2005, and compare these with
      prevalence in 2000. DESIGN: Cross-sectional survey using an anonymous self-report
      questionnaire. SUBJECTS AND METHODS: All 767 VDPs who started practice in the
      summer of 2004 were sent a questionnaire in order to obtain data on the frequency
      and amount of tobacco, alcohol, cannabis and other illicit drugs used before and
      during vocational training (VT). The same survey had been conducted on VDPs five
      years earlier. The analysis was based on 502 subjects who responded and completed
      the questionnaire in 2005 and 534 subjects in 2000. RESULTS: Regular tobacco use
      (10+ cigarettes per day) was reported by 5.4% of males and 4.0% of females in
      2005. This is lower than reported in 2000 (9%) and a statistically significant
      reduction in males. Eighty-two percent of males and 81% of females reported
      alcohol use; a statistically significant reduction from 2000 (89% males and 88%
      females). Reported 'binge drinking' remained high with 44% of males and 39% of
      females drinking at least half the recommended weekly units of alcohol in one
      session, similar to those levels seen in 2000. Thirty-eight percent of males and
      26% of females reported cannabis use during their VT, similar to levels seen in
      2000. Reported use of illicit drugs other than cannabis was less than in 2000.
      Reported illicit drug use was associated with alcohol drinking, and particularly
      with tobacco use. CONCLUSION: This study has found the level of alcohol, tobacco
      and illicit drug use (excluding cannabis) among VDPs decreasing since 2000, but
      levels of binge drinking and cannabis use remaining similar.

PMID- 18084236
TI  - Serum PON1 arylesterase activity in relation to hyperhomocysteinaemia and
      oxidative stress in young adult central retinal venous occlusion patients.
AB  - AIM: To estimate the arylesterase activity of serum paraoxonase-1 (PON1-ARE),
      which is reported to have an antioxidant and antiatherogenic potential and to
      correlate with plasma homocysteine (Hcys) and plasma TBARS in young adult central
      retinal venous occlusion (CRVO) patients. METHODS: A case-control prospective
      study carried out in 10 CRVO patients (mean age 27+/-5 years; 7 males, 3 females)
      and 20 healthy controls (mean age 29+/-5 years; 15 males, 5 females). RESULTS:
      The CRVO patients showed a significantly lowered serum PON1-ARE activity
      (P=0.009) along with a significant increase in the levels of plasma Hcys
      (P=0.018) when compared to the control subjects. There was a negative correlation
      between serum PON1-ARE and plasma Hcys levels (P=0.058) as well as between PON1
      ARE and plasma TBARS levels (P=0.001) in the CRVO patients. CONCLUSION: This is
      the first report of lowered serum PON1-ARE level as a risk factor for CRVO (OR=
      1.108, CI=0.914, 1.314; P=0.296), which is found to correlate with oxidative
      stress.

PMID- 18084237
TI  - Chorioretinal dysplasia, hydranencephaly, and intracranial calcifications: pseudo
      TORCH or a new syndrome?
AB  - PURPOSE: To report the association of severe chorioretinal dysplasia,
      hydranencephaly, microcephaly, and intracranial calcification in children with no
      evidence of intrauterine infections. METHODS: Two unrelated female infants with
      visually inattentive behaviour, hydranencephaly, and intracranial calcification
      were referred for an ophthalmological opinion. RESULTS: The fundus examination
      and computerised tomograms (CT scans) of head were similar in both children.
      There was bilateral extensive chorioretinal dysplasia, intracranial
      calcifications, and hydranencephaly. Serology was negative for acquired
      intrauterine congenital infections. CONCLUSIONS: We report two cases that may
      represent a new syndrome or the more severe end of the spectrum of the pseudo
      TORCH (toxoplasma, rubella, cytomegalovirus, and herpes simplex) syndrome. The
      association of chorioretinal dysplasia with the pseudo-TORCH syndrome has not
      been reported previously.

PMID- 18084238
TI  - BH3 domains define selective inhibitory interactions with BHRF-1 and KSHV BCL-2.
AB  - The Epstein-Barr and Kaposi's sarcoma gamma-herpesviruses (KSHVs) are associated
      with certain cancers, and encode B-cell leukemia/lymphoma 2 (BCL-2) homologs,
      BHRF-1 and KSHV BCL-2, respectively. Little is known, however, about the
      molecular interactions allowing viral BCL-2 homologs to mediate their anti
      apoptotic function. Cellular anti-apoptotic proteins, such as BCL-2 and MCL-1,
      prevent death via selective interactions with pro-death BH3-only proteins. To
      investigate whether BHRF-1 and KSHV BCL-2 function similarly, we made recombinant
      BHRF-1 and KSHV BCL-2 proteins. We identified the individual binding patterns for
      BHRF-1 and KSHV BCL-2 to BH3 domains. These studies surprisingly showed that KSHV
      BCL-2 is more closely related to MCL-1 than to BCL-2, a result confirmed by
      sequence analysis. GST-BHRF-1 and GST-KSHV BCL-2 bound BH3-only family proteins
      from human cells. BHRF-1 protected mammalian cells from growth factor withdrawal,
      etoposide and adriamycin. We found that both BCL-2 and BHRF-1 sequestered pro
      death BH3-only proteins under growth factor-deficient conditions. Finally, we
      tested the ability of a panel of BH3 peptides to inhibit BHRF-1 and KSHV BCL-2
      function in a mitochondrial model of apoptosis. We found that each could be
      inhibited by the select group of BH3 peptides identified in our binding assay.
      Our studies define the biochemical interactions underlying BHRF-1 and KSHV BCL-2
      anti-apoptotic function, and identify peptides that are prototypic inhibitors of
      this function.

PMID- 18084239
TI  - A biochemical analysis of the activation of the Drosophila caspase DRONC.
AB  - The activation of caspases is the principal event in the execution of apoptosis.
      Initiator caspases are activated through an autocatalytic mechanism often
      involving dimerisation or oligomerisation. In Drosophila, the only initiator
      caspase DRONC, is tightly inhibited by DIAP1 and removal of DIAP1 permits
      activation of DRONC by the Drosophila Apaf-1-related killer, ARK. ARK is proposed
      to facilitate DRONC oligomerisation and autoprocessing at residue E352. This
      study examines whether autoprocessing of DRONC is required for its activation and
      for DRONC-mediated cell death. Using purified recombinant proteins, we show here
      that while DRONC autocleaves at residue E352, mutation of this site did not
      abolish enzyme activation, DRICE-induced cleavage of DRONC or DRONC-mediated
      activation of DRICE. We performed a detailed mutational analysis of DRONC
      cleavage sites and show that overexpression of DRONC cleavage mutants in
      Drosophila cells retain pro-apoptotic activity. Using an in vitro cell-free
      assay, we found ARK alone did not activate DRONC and demonstrate a requirement
      for an additional cytosolic factor in ARK-mediated DRONC activation. These
      results suggest that, similar to mammalian caspase-2 and caspase-9, the initial
      cleavage of DRONC is not essential for its activation and suggest a mechanism of
      ARK-mediated DRONC activation different from that proposed previously.

PMID- 18084240
TI  - Bax activation and stress-induced apoptosis delayed by the accumulation of
      cholesterol in mitochondrial membranes.
AB  - Activation of Bax or Bak is essential for the completion of many apoptotic
      programmes. Under cytotoxic conditions, these proteins undergo a series of
      conformational rearrangements that end up with their oligomerization. We found
      that unlike inactive monomeric Bax, active oligomerized Bax is partially
      resistant to trypsin digestion, providing a convenient read out to monitor Bax
      activation. Using this assay, we studied how the lipid composition of membranes
      affects tBid-induced Bax activation in vitro with pure liposomes. We report that
      Bax activation is inhibited by cholesterol and by decreases in membrane fluidity.
      This observation was further tested in vivo using the drug U18666A, which we
      found increases mitochondrial cholesterol levels. When incubated with tBid,
      mitochondria isolated from U18666A-treated cells showed a delay in the release of
      Smac/Diablo and Cytochrome c, as well as in Bax oligomerization. Moreover, pre
      incubation with U18666A partially protected cells from stress-induced apoptosis.
      As many tumours display high mitochondrial cholesterol content, inefficient Bax
      oligomerization might contribute to their resistance to apoptosis-inducing
      agents.

PMID- 18084241
TI  - Cell studies of a three-component antisense MORF/tat/Herceptin nanoparticle
      designed for improved tumor delivery.
AB  - The three-component nanoparticle of this investigation consisted of an anti-type
      I regulatory subunit alpha of the cyclic AMP-dependent protein kinase A (RIalpha)
      antisense phosphorodiamidate morpholino (MORF) oligomer, a tat peptide and the
      anti-HER2 Herceptin antibody each biotinylated and each linked via streptavidin
      and tested in SUM190 (HER2+), SUM149 (HER2-) and SK-BR-3 (HER2+) cells in
      culture, using both radioactivity and fluorescent labels on the antisense and
      control sense MORF. Within the nanoparticle, the antibody provides specific
      binding to the target cells, the tat improves cellular delivery and the MORF
      provides the specific retention of the radioactivity in the target cell nucleus.
      The results show that within the nanoparticle, the Herceptin was still able to
      bind to its determinant; that the MORF escaped entrapment with its mRNA-binding
      ability preserved and that the tat maintained its carrier function. Fluorescence
      microscopy showed evidence of antisense MORF internalization, separation from
      Herceptin and migration to the nucleus. In conclusion, streptavidin appears to
      provide an easy means of mixing and matching components to improve the tumor
      specific targeting, cell membrane transport, pharmacokinetics and other
      properties of antisense and other oligomers. Combining the three components of
      this investigation with streptavidin apparently did not interfere with the
      properties of each component in cell culture and significantly improved delivery.

PMID- 18084242
TI  - Oncolytic virotherapy for ovarian carcinomatosis using a replication-selective
      vaccinia virus armed with a yeast cytosine deaminase gene.
AB  - In this study, we assessed the ability of a highly tumor-selective oncolytic
      vaccinia virus armed with a yeast cytosine deaminase gene to infect and lyse
      human and murine ovarian tumors both in vitro and in vivo. The virus vvDD-CD
      could infect, replicate in and effectively lyse both human and mouse ovarian
      cancer cells in vitro. In two different treatment schedules involving either
      murine MOSEC or human A2780 ovarian carcinomatosis models, regional delivery of
      vvDD-CD selectively targeted tumor cells and ovarian tissue, effectively delaying
      the development of either tumor or ascites and leading to significant survival
      advantages. Oncolytic virotherapy using vvDD-CD in combination with the prodrug 5
      fluorocytosine conferred an additional long-term survival advantage upon tumor
      bearing immunocompetent mice. These findings demonstrate that a tumor-selective
      oncolytic vaccinia combined with gene-directed enzyme prodrug therapy is a highly
      effective strategy for treating advanced ovarian cancers in both syngeneic mouse
      and human xenograft models. Given the biological safety, tumor selectivity and
      oncolytic potency of this armed oncolytic virus, this dual therapy merits further
      investigation as a promising new treatment for metastatic ovarian cancer.

PMID- 18084243
TI  - Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium
      aroA strains secreting prostate-specific antigen and cholera toxin subunit B.
AB  - Prostate cancer is the most common malignant tumor in men and is normally
      associated with increased serum levels of prostate-specific antigen (PSA).
      Therefore, PSA is one potential target for a prostate cancer vaccine. In this
      study we analyzed the functionality of new bacterial PSA vaccines, expressed and
      secreted via the hemolysin (HlyA) secretion system of Escherichia coli, the
      prototype of Type I secretion systems (T1SS) using an attenuated Salmonella
      enterica serovar Typhimurium aroA strain as carrier. The data demonstrate that a
      bacterial live vaccine encompassing T1SS in combination with cholera toxin
      subunit B can be successfully used for delivery of PSA to induce cytotoxic CD8+ T
      cell responses resulting in an efficient prevention of tumor growth in mice.

PMID- 18084244
TI  - Treatment of pulmonary metastatic tumors in mice using lentiviral vector
      engineered stem cells.
AB  - Active cancer immunotherapy relies on functional tumor-specific effector T
      lymphocytes for tumor elimination. Dendritic cells (DCs), as most potent antigen
      presenting cells, have been popularly employed in clinical and experimental tumor
      treatments. We have previously demonstrated that lentiviral vector-mediated
      transgene delivery to DC progenitors, including bone marrow cells and
      hematopoietic stem cells, followed by transplantation supports systemic
      generation of great numbers of tumor antigen-presenting DCs. These DCs
      subsequently stimulate marked and systemic immune activation. Here, we examined
      whether this level of immune activation is sufficient to overcome tumor-induced
      tolerogenic environment for treating an established aggressive epithelial tumor.
      We showed that a combination treatment of granulocyte macrophage-colony
      stimulating factor and cytosine-phosphate-guanine-containing oligonucleotide
      stimulated large numbers of tumor antigen-presenting DCs in situ from transgene
      modified stem cells. Moreover, these in situ generated and activated DCs markedly
      stimulated activation of antigen-specific CD4 and CD8 T cells by augmenting their
      numbers, as well as function, even in a tumor-bearing tolerogenic environment.
      This leads to significant improvement in the therapeutic efficacy of established
      pulmonary metastases. This study suggests that lentiviral vector-modified stem
      cells as DC progenitors may be used as an effective therapeutic regimen for
      treating metastatic epithelial tumors.

PMID- 18084245
TI  - Aberrant fibrillin-1 expression in early emphysematous human lung: a proposed
      predisposition for emphysema.
AB  - Parenchymal destruction, airspace enlargement, and loss of elasticity are
      hallmarks of pulmonary emphysema. Although the basic mechanism is unknown, there
      is a consensus that malfunctioning of the extracellular matrix is a major
      contributor to the pathogenesis of emphysema. In this study, we analyzed the
      expression of the elastic fiber protein fibrillin-1 in a large number (n=69) of
      human lung specimens with early-onset emphysema. Specimens were morphologically
      characterized by the Destructive Index, the Mean Linear Intercept, and the Panel
      Grading. We observed a strong correlation (P<0.001) of aberrant fibrillin-1
      staining with the degree of destruction of lung parenchyma (r=0.71), airspace
      enlargement (r=0.47), and emphysema-related morphological abnormalities (r=0.69).
      There were no obvious correlations with age and smoking behavior. Staining for
      three other extracellular matrix components (type I collagen, type IV collagen,
      and laminin) was not affected. The aberrant fibrillin-1 staining observed in this
      study is similar to that observed in Marfan syndrome, a syndrome caused by
      mutations in the gene encoding fibrillin-1. Strikingly, emphysema is noticed in a
      number of Marfan patients. This, together with the notion that disruption of the
      fibrillin-1 gene in mice results in emphysematous lesions, makes fibrillin-1 a
      strong candidate to be involved in the etiology and pathogenesis of emphysema.

PMID- 18084246
TI  - Pseudoangiomatous stromal hyperplasia tumor: a clinical, radiologic and
      pathologic study of 26 cases.
AB  - Pseudoangiomatous stromal hyperplasia tumors are rare. In this retrospective
      study, we evaluated the clinical, radiologic, and pathologic features of
      pseudoangiomatous stromal hyperplasia tumors and compared histologic findings of
      pseudoangiomatous stromal hyperplasia tumors with clinical outcome. We identified
      26 patients (mean age, 47 years) with pseudoangiomatous stromal hyperplasia
      tumors who had been diagnosed at our institution. Sixteen patients (62%) were
      premenopausal, and 13 (50%) had a history of oral contraceptive or hormone
      replacement therapy use. Ten patients (38%) presented with a palpable mass; in
      the other patients, the tumors were detected by mammography (where it usually
      appeared as a hyperdense mass with irregular margins) or sonography (where it
      usually appeared as a hypoechoic mass). Lesions were a mean of 4.2 cm at the
      largest dimension (range, 0.8-11 cm). Histologically, pseudoangiomatous stromal
      hyperplasia was classified as simple in 18 patients (69%) and
      fascicular/proliferative in eight patients (31%). In one patient (4%), an
      invasive ductal carcinoma was present within the pseudoangiomatous stromal
      hyperplasia tumor. We found associated benign epithelial lesions in eight
      patients (31%) and/or gynecomastia-like changes in 17 patients (65%). The
      presence of gynecomastia-like changes was significantly associated with
      intralobular location of pseudoangiomatous stromal hyperplasia (P=0.00085, by
      Fisher's exact test). Follow-up data were available for 15 patients (mean +/-
      s.d., < or =27 +/- 17 months). No additional pathology or substantial changes in
      existing lesions were found on imaging. All pseudoangiomatous stromal hyperplasia
      tumors diagnosed by core needle biopsy but not subsequently excised remained
      clinically and radiologically stable; therefore, offering the option of close
      clinical surveillance instead of surgery in patients with pseudoangiomatous
      stromal hyperplasia tumors diagnosed by core needle biopsy in selected patients.

PMID- 18084247
TI  - Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in
      thyroid epithelial neoplasms.
AB  - Thyroid-specific transcription factors, Pax8, TTF-1, and TTF-2, are crucial for
      thyroid organogenesis and differentiation. Compared with TTF-1, the other two
      markers have scarcely been investigated in surgical pathology. The goal of this
      study is to evaluate the expressions of these markers in thyroid tumors of the
      full spectrum of differentiation, with special emphasis on anaplastic carcinomas.
      A total of 94 cases of thyroid neoplasms were studied: 17 papillary carcinomas,
      18 follicular adenomas, 16 follicular carcinomas, 7 poorly differentiated
      carcinomas, 28 anaplastic carcinomas, and 8 medullary carcinomas. Immunostains
      for these three markers were performed. The antibodies to Pax8 and TTF-2 were
      also applied on 147 lung carcinomas as well as a variety of normal tissues and
      malignant tumors. All three markers were seen in papillary carcinomas, follicular
      adenomas and carcinomas, and poorly differentiated carcinomas in a diffuse
      manner, whereas their expressions in medullary carcinomas were variable. Pax8 was
      expressed in 79% of anaplastic carcinomas to a variable extent, whereas TTF-1 and
      TTF-2 were seen only in 18 and 7% of anaplastic carcinomas, respectively. TTF-2
      was negative in all other neoplastic and non-neoplastic tissues including those
      of the lung. Pax8 was expressed in renal tubules, fallopian tubes, ovarian
      inclusion cysts, and lymphoid follicles as well as renal carcinoma,
      nephroblastoma, seminoma, and ovarian carcinoma, but not in normal tissue and
      carcinomas of the lung. Pax8 is a useful marker for the diagnosis of anaplastic
      carcinomas, particularly when the differential diagnosis includes pulmonary
      carcinoma. In differentiated thyroid neoplasms, no significant difference in
      expression was seen in all the three transcription factors.

PMID- 18084248
TI  - TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity.
AB  - Squamous cell carcinoma is by far the most common type of cancer of the oral
      cavity, representing more than 90% of all oral cancers. Despite refinement of
      surgical techniques and adjuvant therapies, the prognosis for patients with oral
      squamous cell carcinoma remains poor. Identification of prognostic factors
      related to tumor biology might improve this assessment. Recently, the human
      trophoblast cell-surface antigen TROP2 was found to be highly expressed in
      colorectal cancer, correlating with aggressiveness and poor prognosis. Thus, the
      aim of this study was to investigate TROP2 expression and its prognostic impact
      in oral squamous cell carcinoma patients. TROP2 expression was examined by
      immunohistochemistry in a series of 90 patients on a tissue microarray of
      paraffin-embedded specimens. Survival was calculated using Kaplan-Meier
      estimates. Parameters found to be of prognostic significance in univariate
      analysis were verified in a multivariate Cox regression model. TROP2
      overexpression was observed in 52 (58%) of the tumor samples. Kaplan-Meier curves
      showed that TROP2 overexpression was significantly associated with decreased
      overall survival (P<0.01). Overall survival gradually worsened with increasing
      TROP2 scores. By univariate analyses, no correlation with conventional
      clinicopathological features was found. Multivariate Cox regression analysis
      revealed TROP2 overexpression to be an independent factor predictive of poor
      disease outcome (P<0.01). These results demonstrate that TROP2 overexpression is
      an independent prognostic marker in patients with oral squamous cell carcinoma.
      TROP2 overexpression was detectable in 58% of the tumor samples, indicating it to
      be a potential novel therapeutic target in squamous cell carcinoma of the oral
      cavity.

PMID- 18084249
TI  - The prognostic value of histological grading of posterior fossa ependymomas in
      children: a Children's Oncology Group study and a review of prognostic factors.
AB  - We performed a retrospective analysis of 96 pediatric posterior fossa ependymomas
      in order to determine the prognostic value of histological grade based on the
      current WHO grading scheme. The patients were selected among Children's Oncology
      Group (previously Pediatric Oncology Group-POG) patients enrolled in clinical
      trials, and on the basis of central pathology review, location, and age. We
      excluded entities such as sub-ependymoma, myxopapillary, or clear-cell
      ependymoma, after a consensus diagnosis by three neuropathologists. A total of 66
      males and 30 females with a median age of 48 months were identified. The group
      was analyzed to determine the effects of histological grade, age, gender, and
      extent of resection on event-free and overall survival. Our results showed that
      extent of resection, age, and histological grade were independent prognostic
      variables for event-free survival. The relative risk for extent of resection and
      histological grade was calculated as 3.59 (P<0.001) and 3.58 (P<0.001),
      respectively. Overall survival significantly correlated with extent of resection
      and age, but not with histological grade. We compared our results with peer
      reviewed publications on pediatric intracranial ependymomas in the English
      language between 1990 and 2005. Selection criteria identified 32 manuscripts
      involving 1444 patients. Extent of resection was a significant factor in 21, age
      in 12, and histological grading in nine of these studies. Other factors reported
      to be significant by more than one study included tumor location and radiation
      treatment. Our findings suggest that histological grade (WHO Grade II vs III) is
      an independent prognostic indicator for event-free survival, but may not be so
      for overall survival in pediatric posterior fossa ependymomas. We believe that an
      accurate assessment of the prognostic value of histological grade depends on the
      selection of a well-characterized clinical cohort of sufficient size, and the
      inclusion of relevant histological criteria as outlined in the WHO classification
      scheme.

PMID- 18084250
TI  - WRN promoter methylation possibly connects mucinous differentiation,
      microsatellite instability and CpG island methylator phenotype in colorectal
      cancer.
AB  - Werner syndrome is a premature aging syndrome characterized by early onset of
      cancer and abnormal cellular metabolism of glycosaminoglycan. The WRN helicase
      plays an important role in the maintenance of telomere function. WRN promoter
      methylation and gene silencing are common in colorectal cancer with the CpG
      island methylator phenotype (CIMP), which is associated with microsatellite
      instability (MSI) and mucinous tumors. However, no study has examined the
      relationship between mucinous differentiation, WRN methylation, CIMP and MSI in
      colorectal cancer. Utilizing 903 population-based colorectal cancers and real
      time PCR (MethyLight), we quantified DNA methylation in WRN and eight other
      promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) known
      to be specific for CIMP. Supporting WRN as a good CIMP marker, WRN methylation
      was correlated well with CIMP-high diagnosis (> or =6/8 methylated promoters),
      demonstrating 89% sensitivity and 81% specificity. WRN methylation was associated
      with the presence of any mucinous component and > or =50% mucinous component
      (P<0.0001). Because both MSI and CIMP were associated with mucinous tumors and
      WRN methylation, we stratified tumors into 9 MSI/CIMP subtypes, to examine
      whether the relationship between WRN methylation and mucin still persisted. In
      each MSI/CIMP subtype, tumors with mucinous component were persistently more
      common in WRN-methylated tumors than WRN-unmethylated tumors (P=0.004). No
      relations of WRN methylation with other variables (age, sex, tumor location, poor
      differentiation, signet ring cells, lymphocytic reactions, KRAS, BRAF, p53, p21
      or 18q loss of heterozygosity) persisted after tumors were stratified by CIMP
      status. In conclusion, WRN methylation is associated with mucinous
      differentiation independent of CIMP and MSI status. Our data suggest a possible
      role of WRN methylation in mucinous differentiation, and may provide explanation
      to the enigmatic association between mucin and MSI/CIMP.

PMID- 18084251
TI  - Human prion diseases: from antibody screening to a standardized fast
      immunodiagnosis using automation.
AB  - Demonstration of pathological prion protein accumulation in the central nervous
      system is required to establish the diagnosis of transmissible subacute
      encephalopathies. In humans, this is frequently achieved using prion protein
      immunohistochemistry in paraffin-embedded tissue, a technique that requires
      multiple epitope retrieval and denaturing pretreatments. In addition to being
      time-consuming, this procedure induces tissue alterations that preclude accurate
      morphological examination. The aim of this study was to simplify prion protein
      immunohistochemistry procedure in human tissue, together with increased
      sensitivity and specificity. We screened a panel of 50 monoclonal antibodies
      produced using various immunogens (human and ovine recombinant prion protein,
      prion protein peptides, denatured scrapie-associated fibrils from 263K-infected
      Syrian hamsters) and directed against different epitopes along the human prion
      protein sequence. A panel of different forms of genetic, infectious and sporadic
      transmissible subacute encephalopathies was assessed. The monoclonal 12F10
      antibody provided a high specificity and fast immunodiagnosis with very limited
      denaturing pretreatments. A standardized and reliable fast immunostaining
      procedure was established using an automated diagnostic system (Nexes, Ventana
      Medical Systems) and allowed prion protein detection in the central nervous
      system and in tonsil biopsies. It was evaluated in a series of 300 patients with
      a suspected diagnosis of transmissible subacute encephalopathies and showed high
      sensitivity and specificity.

PMID- 18084252
TI  - PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial
      adenocarcinomas are associated with adverse prognostic parameters.
AB  - Mutations of the oncogene PIK3CA occur frequently in endometrial carcinomas, but
      their prognostic significance is unclear. To determine the clinicopathological
      and molecular implications of these mutations, PIK3CA status was investigated in
      109 endometrial (102 endometrioid and 7 mixed) carcinomas and the results were
      compared with clinicopathological parameters associated with prognosis. Tumors
      were also investigated for microsatellite instability and PTEN, beta-catenin gene
      (CTNNB1), K-RAS, and B-RAF mutations. We found 35 PIK3CA somatic missense
      mutations in 32 (29%) endometrial carcinomas. Eighteen mutations occurred in exon
      20 (kinase domain), and 17 in exon 9 (helical domain). Almost all mutated tumors
      were pure endometrioid adenocarcinomas. All tumors with PIK3CA mutations
      exhibited myometrial invasion (P=0.032). Lymphovascular invasion was found more
      frequently in mutated (28%) than nonmutated carcinomas (18%). Histological grade
      varied significantly according to the location of the PIK3CA mutations whether in
      exon 9 or exon 20 (P=0.033). The frequency of exon 9 mutations was higher in
      grade 1 carcinomas (57%) than in grade 2 (29%) or grade 3 (14%) tumors.
      Conversely, mutations in exon 20 were more common in grade 3 (60%) than in grade
      2 (20%) or grade 1 (20%) carcinomas. None of the tumors confined to the
      endometrium (stage IA) had PIK3CA mutations. Furthermore, whereas 64% of
      adenocarcinomas with exon 9 mutations had invaded < or =(1/2) of the myometrial
      thickness (stage IB), 73% of tumors with exon 20 mutations had either deeper
      myometrial invasion (stage IC) or cervical involvement (stage II) (P=0.045).
      PIK3CA mutations coexisted with microsatellite instability and mutations in PTEN,
      CTNNB1, K-RAS, and B-RAF genes. These results favor that PIK3CA mutations are
      associated with myometrial invasion and, moreover, that tumors harboring PIK3CA
      mutations in exon 20 are frequently high-grade, deeply invasive endometrial
      carcinomas that tend to exhibit lymphovascular invasion.

PMID- 18084253
TI  - Frequent accumulation of nuclear E-cadherin and alterations in the Wnt signaling
      pathway in esophageal squamous cell carcinomas.
AB  - Esophageal squamous cell carcinoma is frequently associated with poor prognosis,
      as a result of high levels of lymph node metastasis. So far, very few genetic
      abnormalities have been associated with this disease, and its molecular etiology
      remains largely unknown. To assess whether the Wnt pathway contributes to
      esophageal squamous cell carcinoma, we characterized the expression and
      subcellular localization of the key Wnt signaling components in all 30 cases of
      esophageal squamous cell carcinomas analyzed. We found abnormal expression and/or
      localization in glycogen synthase kinase-3 alpha/beta (34%), Axin2 (48%), alpha
      catenin (31%), MYC (73%) and cyclin D1 in 46% of cases. Only 13% of tumors showed
      nuclear accumulation of beta-catenin. By contrast, 60% showed nuclear expression
      of E-cadherin using an antibody that recognizes the cytoplasmic domain of E
      cadherin. When the same tumors were stained with antibody raised against the
      extracellular domain of E-cadherin, the expression was lost. A direct correlation
      was found between nuclear E-cadherin and the increased nuclear cyclin D1, one of
      the AP-1 target genes in these tumors. By transfection experiments, the
      cytoplasmic portion of E-cadherin was found to activate the AP-1 transcription
      factor pathway and induced cyclin D1 promoter activity, but beta-catenin/Tcf
      transcription activity was unaffected. Nuclear expression of E-cadherin was also
      detected in tumors other than squamous cell carcinoma, including pancreatic and
      colon cancers, albeit at lower frequency. Nuclear accumulation of a portion of E
      cadherin in esophageal squamous cell carcinoma and the other types of tumors
      indicates that, in addition to the previously implicated tumor suppressor
      activity of E-cadherin, modified forms of this glycoprotein might also play a
      role in growth promotion.

PMID- 18084254
TI  - The intercellular adhesion molecule, cadherin-10, is a marker for human prostate
      luminal epithelial cells that is not expressed in prostate cancer.
AB  - During the normal turnover of prostate epithelium, stem cells in the basal cell
      layer produce an intermediate cell population that gives rise to fully
      differentiated secretory luminal cells. This process is extensively studied in
      relation to the development of prostate disease, in particular, to elucidate the
      origin and nature of prostate cancer. We previously showed that the mRNA of a
      poorly characterised intercellular adhesion molecule, cadherin-10, is strongly
      expressed in human prostate. Using anticadherin-10 antibodies,
      immunohistochemistry, and confocal microscopy, we have examined the pattern of
      cadherin-10 expression in relation to human prostate epithelial differentiation
      markers (E-cadherin, CD44, and cytokeratins (CK) 14, 18 and 19) in archival
      paraffin-embedded and fixed-frozen histopathological specimens in individual and
      serial sections. In non-neoplastic prostate, E-cadherin is expressed by all basal
      and luminal epithelial cells, while cadherin-10 is variably expressed in luminal
      cells where it is colocalised with E-cadherin at basolateral plasma membranes.
      Cadherin-10 is absent in CK14- and/or CD44-positive basal cells, but is expressed
      in CK18-positive luminal cells (differentiated secretory cells), a subset of CK19
      positive intermediate/luminal cells, but not CK19-positive basal cells. Small
      foci of prostate cancer express E-cadherin, CK19 and CK18, but cadherin-10
      expression is low or undetectable. These findings suggest that the expression of
      cadherin-10 is associated with the later stages of differentiation of luminal
      secretory cells, indicating a specific role in secretory cell terminal
      differentiation. While prostate cancer cells express secretory cell markers (eg,
      CK18, prostate-specific antigen) and the more generally expressed E-cadherin,
      their failure to express cadherin-10 further emphasises a role for this cadherin
      in normal prostate organisation and function.

PMID- 18084255
TI  - Human intestinal spirochetosis in Japan; its incidence, clinicopathologic
      features, and genotypic identification.
AB  - Human intestinal spirochetosis is a common condition in Western countries, but is
      not well recognized in Japan. To demonstrate the incidence and clinicopathologic
      findings of human intestinal spirochetosis in Japan, we retrospectively
      investigated biopsy, and endoscopically or surgically resected specimens of the
      large intestine. Among a series of 2556 samples, 11 cases of human intestinal
      spirochetosis were detected (0.4%). Together with additional nine cases
      sporadically found, 20 cases of human intestinal spirochetosis were subjected to
      molecular detection of two strains of spirochetes (Brachyspira aalborgi and
      Brachyspira pilosicoli) by amplifying species-specific portion of 16S ribosomal
      RNA and NADH oxydase gene by polymerase chain reaction. B. aalborgi was detected
      in all cases examined, three of which revealed dual infection of both species.
      Our results suggest that human intestinal spirochetosis infection is relatively
      rare, and B. aalborgi is the most prevalent species in Japan. Most of human
      intestinal spirochetosis were asymptomatic, although symptomatic in exceptional
      cases. In addition, we emphasize a usefulness of immunostaining with anti
      Treponema pallidum and anti-Mycobacterium bovis polyclonal antibodies for
      detecting the spirochetes.

PMID- 18084256
TI  - Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of
      the liver.
AB  - Podoplanin, which is immunoreactive to D2-40 antibody, is reportedly expressed in
      lymphatic vessels in non-neoplastic tissues, and also in vascular and non
      vascular tumors. However, its expression in non-neoplastic and neoplastic liver
      tissues has not been well documented. In this study, we examined podoplanin
      expression in specimens from 10 normal livers and 73 cases of liver tumors:
      hemangioma (16 cases), epithelioid hemangioendothelioma (9 cases), angiosarcoma
      (4 cases), angiomyolipoma (7 cases), hepatocellular carcinoma (11 cases),
      intrahepatic cholangiocarcinoma (11 cases), and metastatic liver cancer (15
      cases). We compared levels of podoplanin and other endothelial markers (CD31,
      CD34, and factor VIII) in liver tumors. In the normal liver, podoplanin was
      expressed in lymphatic endothelium, nerve fibers, and mesothelium in the hepatic
      capsule, but not observed in any cells within hepatic lobules. Among liver
      tumors, podoplanin was specifically expressed in seven of nine cases (78%) of
      epithelioid hemangioendothelioma but not in other hepatic tumors. The expression
      of CD31, CD34, and factor VIII was observed in endothelial cells in all cases of
      hemangioma, epithelioid hemangioendothelioma, angiosarcoma, and angiomyolipoma
      with one exception, a case of epithelioid hemangioendothelioma which was without
      CD31 expression. Interestingly, the intensity of podoplanin expression was
      negatively correlated with the expression of CD34 and factor VIII. In conclusion,
      podoplanin would be useful as a diagnostic marker for epithelioid
      hemangioendothelioma in liver tumors.

PMID- 18084257
TI  - Expression of platelet-derived growth factors and their receptors in ovarian
      clear-cell carcinoma and its putative precursors.
AB  - Recent studies have shown that platelet-derived growth factors and their
      receptors are frequently co-expressed in ovarian cancers. Herein, we investigated
      the role of the platelet-derived growth factor pathway in the development of
      ovarian clear-cell adenocarcinoma, a highly chemoresistant form of ovarian
      cancer. Immunohistochemical expression of platelet-derived growth factor receptor
      alpha and receptor-beta, platelet-derived growth factor A-chain and B-chain was
      examined in 31 cases of clear-cell adenocarcinoma and 56 coexisting putative
      precursor lesions: 17 non-atypical and 19 atypical endometrioses, and 10 non
      atypical and 10 atypical clear-cell adenofibroma components. Twenty-one solitary
      endometrioses were also examined. Vascular endothelial cells were always positive
      for all the markers examined, and were used as positive controls. The frequencies
      of positivity for platelet-derived growth factor receptor-alpha and receptor
      beta, and platelet-derived growth factor A-chain increased in accordance with
      higher cytologic atypia in the putative precursors: 71, 47, and 59% in the 17 non
      atypical endometrioses, 84, 73, and 84% in the 19 atypical endometrioses, 0% each
      in the 10 non-atypical clear-cell adenofibromas, 100, 90, and 90% in the 10
      atypical clear-cell adenofibromas, and 97, 97, and 100% in the 31 clear-cell
      adenocarcinomas, respectively. Positivity for platelet-derived growth factor B
      chain increased in accordance with increased atypia in clear-cell adenofibroma:
      0% in non-atypical clear-cell adenofibromas, 30% in atypical clear-cell
      adenofibromas, and 60% in coexisting carcinomas. However, in contrast, positivity
      for platelet-derived growth factor B-chain decreased in accordance with increased
      atypia in endometriosis coexisting with clear-cell adenocarcinomas: 35% in non
      atypical endometrioses, 11% in atypical endometrioses, and 5% in coexisting
      carcinomas. Platelet-derived growth factor receptor-alpha and receptor-beta, and
      their ligands A-chain and B-chain were positive in 14, 29, 19, and 62% of the
      solitary endometrioses, respectively. These results indicate activation of the
      platelet-derived growth factor pathway in ovarian clear-cell adenocarcinomas and
      suggest biological differences between carcinomas that arise in association with
      clear-cell adenofibroma vs endometriosis.

PMID- 18084258
TI  - Hierarchical cluster analysis of myoepithelial/basal cell markers in adenoid
      cystic carcinoma and polymorphous low-grade adenocarcinoma.
AB  - Distinguishing adenoid cystic carcinoma from polymorphous low-grade
      adenocarcinoma of the salivary glands is important for their management. We
      studied the expression of several myoepithelial and basal/stem cell markers
      (smooth muscle actin, calponin, smooth muscle myosin heavy chain,
      metallothionein, maspin, and p63) by immunohistochemistry in 23 adenoid cystic
      carcinoma and 24 polymorphous low-grade adenocarcinoma, to identify the most
      useful marker or combination of markers that may help their diagnoses. The
      results were analyzed using hierarchical cluster analysis and chi(2) test for
      trend. We noted diffuse expression of smooth muscle actin in 20 adenoid cystic
      carcinoma vs one polymorphous low-grade adenocarcinoma (P<0.0001), calponin in 15
      adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P<0.0001),
      smooth muscle myosin heavy chain in 15 adenoid cystic carcinoma vs one
      polymorphous low-grade adenocarcinoma (P=0.001), metallothionein in 22 adenoid
      cystic carcinoma vs eight polymorphous low-grade adenocarcinoma (P<0.001), maspin
      in 22 adenoid cystic carcinoma vs 14 polymorphous low-grade adenocarcinoma, and
      p63 in 21 adenoid cystic carcinoma vs 14 polymorphous low-grade adenocarcinoma.
      Hierarchical clustering of smooth muscle actin, calponin, smooth muscle myosin
      heavy chain, and metallothionein was virtually identical (kappa< or =0.0035),
      suggesting no significant advantage to their use in combination than
      individually. Diffuse smooth muscle actin expression showed the highest accuracy
      (91.5%) and positive predictive value (95.2%) for adenoid cystic carcinoma. Thus,
      diffuse expression of smooth muscle actin, calponin, smooth muscle myosin heavy
      chain, and metallothionein was highly predictive of adenoid cystic carcinoma,
      whereas maspin and p63 were frequently expressed in both tumors. In
      differentiating adenoid cystic carcinoma from polymorphous low-grade
      adenocarcinoma, smooth muscle actin as a single ancillary test in support of the
      histological findings, appears to be as efficient as multiple immunohistochemical
      tests.

PMID- 18084259
TI  - Silent mutations in KIT and PDGFRA and coexpression of receptors with SCF and
      PDGFA in Merkel cell carcinoma: implications for tyrosine kinase-based
      tumorigenesis.
AB  - Merkel cell carcinoma is a rare and aggressive form of skin cancer of
      neuroendocrine origin. Its treatment involves wide excision and radiotherapy but
      no effective therapy exists for advanced disease. Upregulation of the platelet
      derived growth factor receptor family of tyrosine kinases, PDGFRA and KIT, has a
      crucial role in cancer development. Several studies have shown expression of the
      tyrosine kinase receptor KIT (CD117) in Merkel cell carcinoma. In this study, we
      examined the expression and mutational status of KIT and PDGFRA in 14 primary and
      18 metastatic Merkel cell carcinoma. The expression of KIT and PDGFRA and their
      respective ligands, stem cell factor (SCF) and PDGFA, was assessed by
      immunohistochemistry. In addition, we analyzed KIT exons 9, 11, 13 and 17, and
      PDGFRA exons 10, 12 and 18 for the presence of activating mutations. We found
      that only 53% of cases of Merkel cell carcinoma expressed KIT, which was mostly
      seen as diffuse weak staining, and SCF expression was observed only in 31% of
      cases. In contrast, 87 and 81% of cases expressed PDGFRA and PDGFA, respectively.
      We observed coexpression of SCF and KIT in only 5 of 32 cases (16%) whereas 25 of
      31 cases (81%) showed coexpression of PDGFRA and its ligand PDGFA. While we
      documented silent mutations in exon 17 of KIT and exons 10, 12 and 18 of PDGFRA,
      we were not able to identify any known activating mutations. Our results indicate
      that there is no correlation between positive immunostaining and occurrence of
      activating mutations in KIT and PDGFRA. Moreover, the presence of KIT/SCF and
      PDGFRA/PDGFA coexpression in a proportion of cases may indicate an
      autocrine/paracrine stimulation loop. We think therefore that imatinib mesylate
      is less likely to be an effective therapy for Merkel cell carcinoma, unless
      activating mutations exist in other exons of these receptor kinases.

PMID- 18084261
TI  - What does serum fibroblast growth factor 23 do in hemodialysis patients?
AB  - Fibroblast growth factor 23 (FGF-23) is a phosphate-regulating substance largely
      produced by osteocytes. Its major action, in normal subjects, is the inhibition
      of Na-coupled reabsorption of inorganic phosphate in the renal proximal tubule.
      FGF-23 levels increase markedly in dialysis patients. Why do the FGF-23 levels
      increase in these patients, and do they have any physiologic or pathophysiologic
      effects?

PMID- 18084262
TI  - Dual role of the activated epidermal growth factor receptor in renal tubular
      cells during stress.
AB  - The paper by Sarro et al. raises the therapeutically important possibility that
      activation of the epidermal growth factor receptor (EGFR) after proximal tubule
      injury serves an unexpected death function and the EGFR-mediated survival
      signaling can be restored by identification of parallel and interacting pathways.

PMID- 18084263
TI  - Innate immunity as a driving force in renal disease.
AB  - Mrug et al. propose that innate immunity is a hallmark of progressive polycystic
      kidney disease (PKD). We propose that innate immunity is a driving force in the
      progression of many renal diseases. Renal epithelial cells are capable of
      expressing a large variety of proinflammatory genes resulting in the production
      of cytokines, chemokines, cell-adhesion molecules, and complement components. We
      suggest that future therapeutic interventions should be directed toward control
      of innate immunity in renal disease.

PMID- 18084265
TI  - The case | Sterile pyuria and an abnormal abdominal film. "Autonephrectomy" of
      right kidney.

PMID- 18084266
TI  - Minimally invasive treatment of bilateral ureteropelvic obstruction with massive
      calculi.

PMID- 18084267
TI  - An unusual case of forehead post-transplant lymphoproliferative disease.

PMID- 18084270
TI  - Searching for a wrench to throw into the splicing machine.

PMID- 18084272
TI  - Engineering ingenuity at iGEM.

PMID- 18084271
TI  - Drugs in action.

PMID- 18084273
TI  - Small-molecule dissection of BMP signaling.

PMID- 18084274
TI  - IP7 guards the CDK gate.

PMID- 18084275
TI  - SAR by HCS.

PMID- 18084276
TI  - Chemical "knockout" challenges the amphotericin B channel model.

PMID- 18084277
TI  - What determines the speed limit on enzyme catalysis?

PMID- 18084279
TI  - Modifying murine von Willebrand factor A1 domain for in vivo assessment of human
      platelet therapies.
AB  - The A1 domain of von Willebrand factor (VWF-A1) plays a crucial role in
      hemostasis and thrombosis by initiating platelet adhesion at sites of arterial
      injury through interactions with the platelet receptor glycoprotein Ib alpha
      (GPIbalpha). Here we report that murine VWF-A1 supports limited binding of human
      platelets. However, atomic models of GPIbalpha-VWF-A1 complexes identified an
      electrostatic 'hot-spot' that, when mutated in murine VWF-A1, switches its
      binding specificity from mouse to human GPIbalpha. Furthermore, mice expressing
      this mutant VWF-A1 display a bleeding phenotype that can be corrected by infusion
      of human platelets. Mechanistically, human platelets correct the phenotype by
      forming occlusive thrombi, an event that can be abrogated by blockade of
      GPIbalpha or by the preadministration of inhibitors of platelet activation or
      adhesion (clopidogrel (Plavix) and abciximab (ReoPro), respectively). Thus, by
      modifying a protein interface, we have generated a potential biological platform
      for preclinical screening of antithrombotics that specifically target human
      platelets.

PMID- 18084280
TI  - Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain
      self-renewability during mammalian neurogenesis.
AB  - During mammalian development, neuroepithelial cells function as mitotic
      progenitors, which self-renew and generate neurons. Although spindle orientation
      is important for such polarized cells to undergo symmetric or asymmetric
      divisions, its role in mammalian neurogenesis remains unclear. Here we show that
      control of spindle orientation is essential in maintaining the population of
      neuroepithelial cells, but dispensable for the decision to either proliferate or
      differentiate. Knocking out LGN, (the G protein regulator), randomized the
      orientation of normally planar neuroepithelial divisions. The resultant loss of
      the apical membrane from daughter cells frequently converted them into abnormally
      localized progenitors without affecting neuronal production rate. Furthermore,
      overexpression of Inscuteable to induce vertical neuroepithelial divisions
      shifted the fate of daughter cells. Our results suggest that planar mitosis
      ensures the self-renewal of neuroepithelial progenitors by one daughter
      inheriting both apical and basal compartments during neurogenesis.

PMID- 18084281
TI  - GEP100 links epidermal growth factor receptor signalling to Arf6 activation to
      induce breast cancer invasion.
AB  - Epidermal growth factor (EGF) receptor (EGFR) signalling is implicated in tumour
      invasion and metastasis. However, whether there are EGFR signalling pathways
      specifically used for tumour invasion still remains elusive. Overexpression of
      Arf6 and its effector, AMAP1, correlates with and is crucial for the invasive
      phenotypes of different breast cancer cells. Here we identify the mechanism by
      which Arf6 is activated to induce tumour invasion. We found that GEP100/BRAG2, a
      guanine nucleotide exchanging factor (GEF) for Arf6, is responsible for the
      invasive activity of MDA-MB-231 breast cancer cells, whereas the other ArfGEFs
      are not. GEP100, through its pleckstrin homology domain, bound directly to
      Tyr1068/1086-phosphorylated EGFR to activate Arf6. Overexpression of GEP100,
      together with Arf6, caused non-invasive MCF7 cells to become invasive, which was
      dependent on EGF stimulation. Moreover, GEP100 knockdown blocked tumour
      metastasis. GEP100 was expressed in 70% of primary breast ductal carcinomas, and
      was preferentially co-expressed with EGFR in the malignant cases. Our results
      indicate that GEP100 links EGFR signalling to Arf6 activation to induce invasive
      activities of some breast cancer cells, and hence may contribute to their
      metastasis and malignancy.

PMID- 18084282
TI  - Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and
      non-ciliary mechanisms.
AB  - Primary cilia are microtubule-based organelles involved in signal transduction
      and project from the surface of most vertebrate cells. Proteins that can localize
      to the cilium, for example, Inversin and Bardet-Biedl syndrome (BBS) proteins,
      are implicated in both beta-catenin-dependent and -independent Wnt signalling.
      Given that Inversin and BBS proteins are found both at the cilium and elsewhere
      in the cell, the role of the cilium itself in Wnt signalling is not clear. Using
      three separate mutations that disrupt ciliogenesis (affecting Kif3a, Ift88 and
      Ofd1), we show in this study that the primary cilium restricts the activity of
      the canonical Wnt pathway in mouse embryos, primary fibroblasts, and embryonic
      stem cells. Interestingly, unciliated cells activate transcription only in
      response to Wnt stimulation, but do so much more robustly than ciliated cells.
      Loss of Kif3a, but not other ciliogenic genes, causes constitutive
      phosphorylation of Dishevelled (Dvl). Blocking the activity of casein kinase I
      (CKI) reverses this constitutive Dvl phosphorylation and abrogates pathway hyper
      responsiveness. These results suggest that Kif3a restrains canonical Wnt
      signalling both by restricting the CKI-dependent phosphorylation of Dvl and
      through a separate ciliary mechanism. More generally, these findings reveal that,
      in contrast to its role in promoting Hedgehog (Hh) signalling, the cilium
      restrains canonical Wnt signalling.

PMID- 18084283
TI  - Epithelial coating controls mesenchymal shape change through tissue-positioning
      effects and reduction of surface-minimizing tension.
AB  - Signalling between mesenchymal and epithelial cells has a profound influence on
      organ morphogenesis. However, less is known about the mechanical function of
      epithelial-mesenchymal interactions. Here, we describe two principal effects by
      which epithelia can regulate shape changes in mesenchymal cell aggregates. We
      propose that during formation of the embryonic body axis, the epithelial layer
      relieves surface minimizing tensions that would force cell aggregates into a
      spherical shape, and controls the serial arrangement of cell populations along
      the axis. The combined effects permit the tissue to deviate from a spherical form
      and to elongate.

PMID- 18084284
TI  - Unified mode of centromeric protection by shugoshin in mammalian oocytes and
      somatic cells.
AB  - Reductional chromosome segregation in germ cells, where sister chromatids are
      pulled to the same pole, accompanies the protection of cohesin at centromeres
      from separase cleavage. Here, we show that mammalian shugoshin Sgo2 is expressed
      in germ cells and is solely responsible for the centromeric localization of PP2A
      and the protection of cohesin Rec8 in oocytes, proving conservation of the
      mechanism from yeast to mammals. However, this role of Sgo2 contrasts with its
      mitotic role in protecting centromeric cohesin only from prophase dissociation,
      but never from anaphase cleavage. We demonstrate that, in somatic cells,
      shugoshin colocalizes with cohesin in prophase or prometaphase, but their
      localizations become separate when centromeres are pulled oppositely at
      metaphase. Remarkably, if tension is artificially removed from the centromeres at
      the metaphase-anaphase transition, cohesin at the centromeres can be protected
      from separase cleavage even in somatic cells, as in germ cells. These results
      argue for a unified view of centromeric protection by shugoshin in mitosis and
      meiosis.

PMID- 18084285
TI  - ARF1 is directly involved in dynamin-independent endocytosis.
AB  - Endocytosis of glycosylphosphatidyl inositol (GPI)-anchored proteins (GPI-APs)
      and the fluid phase takes place primarily through a dynamin- and clathrin
      independent, Cdc42-regulated pinocytic mechanism. This mechanism is mediated by
      primary carriers called clathrin-independent carriers (CLICs), which fuse to form
      tubular early endocytic compartments called GPI-AP enriched endosomal
      compartments (GEECs). Here, we show that reduction in activity or levels of ARF1
      specifically inhibits GPI-AP and fluid-phase endocytosis without affecting other
      clathrin-dependent or independent endocytic pathways. ARF1 is activated at
      distinct sites on the plasma membrane, and by the recruitment of RhoGAP domain
      containing protein, ARHGAP10, to the plasma membrane, modulates cell-surface
      Cdc42 dynamics. This results in the coupling of ARF1 and Cdc42 activity to
      regulate endocytosis at the plasma membrane. These findings provide a molecular
      basis for a crosstalk of endocytosis with secretion by the sharing of a key
      regulator of secretory traffic, ARF1.

PMID- 18084286
TI  - Activity-dependent gating of lateral inhibition in the mouse olfactory bulb.
AB  - Lateral inhibition is a circuit motif found throughout the nervous system that
      often generates contrast enhancement and center-surround receptive fields. We
      investigated the functional properties of the circuits mediating lateral
      inhibition between olfactory bulb principal neurons (mitral cells) in vitro. We
      found that the lateral inhibition received by mitral cells is gated by
      postsynaptic firing, such that a minimum threshold of postsynaptic activity is
      required before effective lateral inhibition is recruited. This dynamic
      regulation allows the strength of lateral inhibition to be enhanced between cells
      with correlated activity. Simulations show that this regulation of lateral
      inhibition causes decorrelation of mitral cell activity that is evoked by similar
      stimuli, even when stimuli have no clear spatial structure. These results show
      that this previously unknown mechanism for specifying lateral inhibitory
      connections allows functional inhibitory connectivity to be dynamically remapped
      to relevant populations of neurons.

PMID- 18084287
TI  - On and off domains of geniculate afferents in cat primary visual cortex.
AB  - On- and off-center geniculate afferents form two major channels of visual
      processing that are thought to converge in the primary visual cortex. However,
      humans with severely reduced on responses can have normal visual acuity when
      tested in a white background, which indicates that off channels can function
      relatively independently from on channels under certain conditions. Consistent
      with this functional independence of channels, we demonstrate here that on- and
      off-center geniculate afferents segregate in different domains of the cat primary
      visual cortex and that off responses dominate the cortical representation of the
      area centralis. On average, 70% of the geniculate afferents converging at the
      same cortical domain had receptive fields of the same contrast polarity.
      Moreover, off-center afferents dominated the representation of the area centralis
      in the cortex, but not in the thalamus, indicating that on- and off-center
      afferents are balanced in number, but not in the amount of cortical territory
      that they cover.

PMID- 18084288
TI  - A thermosensory pathway that controls body temperature.
AB  - Defending body temperature against environmental thermal challenges is one of the
      most fundamental homeostatic functions that are governed by the nervous system.
      Here we describe a somatosensory pathway that essentially constitutes the
      afferent arm of the thermoregulatory reflex that is triggered by cutaneous
      sensation of environmental temperature changes. Using in vivo
      electrophysiological and anatomical approaches in the rat, we found that lateral
      parabrachial neurons are pivotal in this pathway by glutamatergically
      transmitting cutaneous thermosensory signals received from spinal somatosensory
      neurons directly to the thermoregulatory command center, the preoptic area. This
      feedforward pathway mediates not only sympathetic and shivering thermogenic
      responses but also metabolic and cardiac responses to skin cooling challenges.
      Notably, this 'thermoregulatory afferent' pathway exists in parallel with the
      spinothalamocortical somatosensory pathway that mediates temperature perception.
      These findings make an important contribution to our understanding of both the
      somatosensory system and thermal homeostasis -- two mechanisms that are
      fundamental to the nervous system and to our survival.

PMID- 18084289
TI  - MuSK controls where motor axons grow and form synapses.
AB  - Motor axons approach muscles that are regionally prespecialized, as acetylcholine
      receptors are clustered in the central region of muscle before and independently
      of innervation. This muscle prepattern requires MuSK, a receptor tyrosine kinase
      that is essential for synapse formation. It is not known how muscle prepatterning
      is established, and whether motor axons recognize this prepattern. Here we show
      that expression of Musk is prepatterned in muscle and that early Musk expression
      in developing myotubes is sufficient to establish muscle prepatterning. We
      further show that ectopic Musk expression promotes ectopic synapse formation,
      indicating that muscle prepatterning normally has an instructive role in
      directing where synapses will form. In addition, ectopic Musk expression
      stimulates synapse formation in the absence of Agrin and rescues the lethality of
      Agrn mutant mice, demonstrating that the postsynaptic cell, and MuSK in
      particular, has a potent role in regulating the formation of synapses.

PMID- 18084290
TI  - ITPKC functional polymorphism associated with Kawasaki disease susceptibility and
      formation of coronary artery aneurysms.
AB  - Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which
      a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the
      inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that
      is significantly associated with Kawasaki disease susceptibility and also with an
      increased risk of coronary artery lesions in both Japanese and US children.
      Transfection experiments showed that the C allele of itpkc_3 reduces splicing
      efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell
      activation through the Ca2+/NFAT signaling pathway, and the C allele may
      contribute to immune hyper-reactivity in Kawasaki disease. This finding provides
      new insights into the mechanisms of immune activation in Kawasaki disease and
      emphasizes the importance of activated T cells in the pathogenesis of this
      vasculitis.

PMID- 18084291
TI  - Genetic variation in DPP6 is associated with susceptibility to amyotrophic
      lateral sclerosis.
AB  - We identified a SNP in the DPP6 gene that is consistently strongly associated
      with susceptibility to amyotrophic lateral sclerosis (ALS) in different
      populations of European ancestry, with an overall P value of 5.04 x 10(-8) in
      1,767 cases and 1,916 healthy controls and with an odds ratio of 1.30 (95%
      confidence interval (CI) of 1.18-1.43). Our finding is the first report of a
      genome-wide significant association with sporadic ALS and may be a target for
      future functional studies.

PMID- 18084292
TI  - Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence
      colorectal cancer risk.
AB  - We mapped a high-penetrance gene (CRAC1; also known as HMPS) associated with
      colorectal cancer (CRC) in the Ashkenazi population to a 0.6-Mb region on
      chromosome 15 containing SCG5 (also known as SGNE1), GREM1 and FMN1. We
      hypothesized that the CRAC1 locus harbored low-penetrance variants that increased
      CRC risk in the general population. In a large series of colorectal cancer cases
      and controls, SNPs near GREM1 and SCG5 were strongly associated with increased
      CRC risk (for rs4779584, P = 4.44 x 10(-14)).

PMID- 18084293
TI  - RNA toxicity in myotonic muscular dystrophy induces NKX2-5 expression.
AB  - Myotonic muscular dystrophy (DM1) is the most common inherited neuromuscular
      disorder in adults and is considered the first example of a disease caused by RNA
      toxicity. Using a reversible transgenic mouse model of RNA toxicity in DM1, we
      provide evidence that DM1 is associated with induced NKX2-5 expression. Transgene
      expression resulted in cardiac conduction defects, increased expression of the
      cardiac-specific transcription factor NKX2-5 and profound disturbances in
      connexin 40 and connexin 43. Notably, overexpression of the DMPK 3' UTR mRNA in
      mouse skeletal muscle also induced transcriptional activation of Nkx2-5 and its
      targets. In human muscles, these changes were specific to DM1 and were not
      present in other muscular dystrophies. The effects on NKX2-5 and its downstream
      targets were reversed by silencing toxic RNA expression. Furthermore, using Nkx2
      5+/- mice, we show that NKX2-5 is the first genetic modifier of DM1-associated
      RNA toxicity in the heart.

PMID- 18084295
TI  - Electrically driven phase transition in magnetite nanostructures.
AB  - Magnetite (Fe3O4), an archetypal transition-metal oxide, has been used for
      thousands of years, from lodestones in primitive compasses to a candidate
      material for magnetoelectronic devices. In 1939, Verwey found that bulk magnetite
      undergoes a transition at TV approximately 120 K from a high-temperature 'bad
      metal' conducting phase to a low-temperature insulating phase. He suggested that
      high-temperature conduction is through the fluctuating and correlated valences of
      the octahedral iron atoms, and that the transition is the onset of charge
      ordering on cooling. The Verwey transition mechanism and the question of charge
      ordering remain highly controversial. Here, we show that magnetite nanocrystals
      and single-crystal thin films exhibit an electrically driven phase transition
      below the Verwey temperature. The signature of this transition is the onset of
      sharp conductance switching in high electric fields, hysteretic in voltage. We
      demonstrate that this transition is not due to local heating, but instead is due
      to the breakdown of the correlated insulating state when driven out of
      equilibrium by electrical bias. We anticipate that further studies of this newly
      observed transition and its low-temperature conducting phase will shed light on
      how charge ordering and vibrational degrees of freedom determine the ground state
      of this important compound.

PMID- 18084294
TI  - 'Tuning' of type I interferon-induced Jak-STAT1 signaling by calcium-dependent
      kinases in macrophages.
AB  - Immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors modulate
      the amplitude and nature of macrophage responses to Toll-like receptor and
      cytokine receptor stimulation. However, the molecular mechanisms enabling this
      receptor crosstalk are not known. Here we investigated the function of the
      calcium-dependent kinases CaMK and Pyk2 'downstream' of ITAM-associated receptors
      in the regulation of cytokine-induced activation of Jak kinases and STAT
      transcription factors. CaMK and Pyk2 relayed signals from integrins and the ITAM
      containing adaptor DAP12 to augment interleukin 10- and interferon-alpha-induced
      Jak activation and STAT1-dependent gene expression. CaMK inhibition suppressed
      STAT1-mediated interferon-alpha signaling in a mouse model of systemic lupus
      erythematosus. Our results associate Pyk2 and Jak kinases with the linkage of
      signals emanating from cytokine and heterologous ITAM-dependent receptors.

PMID- 18084296
TI  - Effects of elastic anisotropy on strain distributions in decahedral gold
      nanoparticles.
AB  - Metallic nanoparticles exhibit exceptional optoelectronic properties with
      applications in plasmonics, biosensing and nanomedicine. Recently, new synthesis
      techniques have enabled precise control over the sizes and shapes of metal
      nanoparticles, occasionally leading to morphologies that cannot be properly
      characterized using standard techniques. An example is five-fold-twinned
      decahedral Au nanoparticles, which are intrinsically strained as a result of
      their unique geometry. Various competing models have been proposed to predict the
      strain states of such nanoparticles. Here, we present a detailed analysis of the
      internal structure of a decahedral Au nanoparticle using aberration-corrected
      high-resolution electron microscopy and strain mapping. Our measurements confirm
      the presence of a disclination, which is consistent with the commonly accepted
      strain model. However, we also observed shear gradients, which are absent from
      the models. By comparing our local strain determinations with finite-element
      calculations, we show the effect of elastic anisotropy on the strain state in
      these nanoparticles.

PMID- 18084297
TI  - A proteome chip approach reveals new DNA damage recognition activities in
      Escherichia coli.
AB  - Despite the fact that many genomes have been decoded, proteome chips comprising
      individually purified proteins have been reported only for budding yeast, mainly
      because of the complexity and difficulty of high-throughput protein purification.
      To facilitate proteomics studies in prokaryotes, we have developed a high
      throughput protein purification protocol that allowed us to purify 4,256 proteins
      encoded by the Escherichia coli K12 strain within 10 h. The purified proteins
      were then spotted onto glass slides to create E. coli proteome chips. We used
      these chips to develop assays for identifying proteins involved in the
      recognition of potential base damage in DNA. By using a group of DNA probes, each
      containing a mismatched base pair or an abasic site, we found a small number of
      proteins that could recognize each type of probe with high affinity and
      specificity. We further evaluated two of these proteins, YbaZ and YbcN, by
      biochemical analyses. The assembly of libraries containing DNA probes with
      specific modifications and the availability of E. coli proteome chips have the
      potential to reveal important interactions between proteins and nucleic acids
      that are time-consuming and difficult to detect using other techniques.

PMID- 18084298
TI  - Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic
      resonance imaging.
AB  - We have developed a method for integrating three dimensional-volume
      reconstructions of spatially resolved matrix-assisted laser desorption/ionization
      imaging mass spectrometry (MALDI IMS) ion images of whole mouse heads with high
      resolution images from other modalities in an animal-specific manner. This
      approach enabled us to analyze proteomic profiles from MALDI IMS data with
      corresponding in vivo data provided by magnetic resonance imaging.

PMID- 18084299
TI  - Vector and parameters for targeted transgenic RNA interference in Drosophila
      melanogaster.
AB  - The conditional expression of hairpin constructs in Drosophila melanogaster has
      emerged in recent years as a method of choice in functional genomic studies. To
      date, upstream activating site-driven RNA interference constructs have been
      inserted into the genome randomly using P-element-mediated transformation, which
      can result in false negatives due to variable expression. To avoid this problem,
      we have developed a transgenic RNA interference vector based on the phiC31 site
      specific integration method.

PMID- 18084300
TI  - Tracking transmitter-gated P2X cation channel activation in vitro and in vivo.
AB  - We present a noninvasive approach to track activation of ATP-gated P2X receptors
      and potentially other transmitter-gated cation channels that show calcium fluxes.
      We genetically engineered rat P2X receptors to carry calcium sensors near the
      channel pore and tested this as a reporter for P2X(2) receptor opening. The
      method has several advantages over previous attempts to image P2X channel
      activation by fluorescence resonance energy transfer (FRET): notably, it reports
      channel opening rather than a conformation change in the receptor protein. Our
      FRET-based imaging approach can be used as a general method to track, in real
      time, the location, regional expression variation, mobility and activation of
      transmitter-gated P2X channels in living neurons in vitro and in vivo. This
      approach should help to determine when, where and how different receptors are
      activated during physiological processes.

PMID- 18084301
TI  - Modification of kidney barrier function by the urokinase receptor.
AB  - Podocyte dysfunction, represented by foot process effacement and proteinuria, is
      often the starting point for progressive kidney disease. Therapies aimed at the
      cellular level of the disease are currently not available. Here we show that
      induction of urokinase receptor (uPAR) signaling in podocytes leads to foot
      process effacement and urinary protein loss via a mechanism that includes lipid
      dependent activation of alphavbeta3 integrin. Mice lacking uPAR (Plaur-/-) are
      protected from lipopolysaccharide (LPS)-mediated proteinuria but develop disease
      after expression of a constitutively active beta3 integrin. Gene transfer studies
      reveal a prerequisite for uPAR expression in podocytes, but not in endothelial
      cells, for the development of LPS-mediated proteinuria. Mechanistically, uPAR is
      required to activate alphavbeta3 integrin in podocytes, promoting cell motility
      and activation of the small GTPases Cdc42 and Rac1. Blockade of alphavbeta3
      integrin reduces podocyte motility in vitro and lowers proteinuria in mice. Our
      findings show a physiological role for uPAR signaling in the regulation of kidney
      permeability.

PMID- 18084302
TI  - G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt
      induced hypertension.
AB  - The tone of vascular smooth muscle cells is a primary determinant of the total
      peripheral vascular resistance and hence the arterial blood pressure. Most forms
      of hypertension ultimately result from an increased vascular tone that leads to
      an elevated total peripheral resistance. Regulation of vascular resistance under
      normotensive and hypertensive conditions involves multiple mediators, many of
      which act through G protein-coupled receptors on vascular smooth muscle cells.
      Receptors that mediate vasoconstriction couple with the G-proteins G(q)-G11 and
      G12-G13 to stimulate phosphorylation of myosin light chain (MLC) via the Ca2+/MLC
      kinase- and Rho/Rho kinase-mediated signaling pathways, respectively. Using
      genetically altered mouse models that allow for the acute abrogation of both
      signaling pathways by inducible Cre/loxP-mediated mutagenesis in smooth muscle
      cells, we show that G(q)-G11-mediated signaling in smooth muscle cells is
      required for maintenance of basal blood pressure and for the development of salt
      induced hypertension. In contrast, lack of G12-G13, as well as of their major
      effector, the leukemia-associated Rho guanine nucleotide exchange factor (LARG),
      did not alter normal blood pressure regulation but did block the development of
      salt-induced hypertension. This identifies the G12-G13-LARG-mediated signaling
      pathway as a new target for antihypertensive therapies that would be expected to
      leave normal blood pressure regulation unaffected.

PMID- 18084303
TI  - Structural basis for synaptic adhesion mediated by neuroligin-neurexin
      interactions.
AB  - The heterophilic synaptic adhesion molecules neuroligins and neurexins are
      essential for establishing and maintaining neuronal circuits by modulating the
      formation and maturation of synapses. The neuroligin-neurexin adhesion is Ca2+
      dependent and regulated by alternative splicing. We report a structure of the
      complex at a resolution of 2.4 A between the mouse neuroligin-1 (NL1)
      cholinesterase-like domain and the mouse neurexin-1beta (NX1beta) LNS (laminin,
      neurexin and sex hormone-binding globulin-like) domain. The structure revealed a
      delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca2+-mediated
      and solvent-supplemented interface, rendering it capable of being modulated by
      alternative splicing and other regulatory factors. Thermodynamic data supported a
      mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at the
      edge of the NL1-NX1beta interface. Mapping neuroligin mutations implicated in
      autism indicated that most such mutations are structurally destabilizing,
      supporting deficient neuroligin biosynthesis and processing as a common cause for
      this brain disorder.

PMID- 18084305
TI  - Structural basis for the catalytic mechanism of phosphothreonine lyase.
AB  - Salmonella SpvC belongs to a new enzyme family designated phosphothreonine lyases
      that irreversibly inactivate mitogen-activated protein kinases. The crystal
      structure of SpvC reported here reveals that the two phosphorylated residues in
      the substrate peptide predominantly mediate its recognition by SpvC. Substrate
      induced conformational changes in SpvC sequester the phosphothreonine in a
      completely solvent-free environment, preventing the hydrolysis of the phosphate
      group and facilitating the elimination reaction.

PMID- 18084304
TI  - Structural basis for activation of the autoinhibitory C-terminal kinase domain of
      p90 RSK2.
AB  - The X-ray structure at 2.0-A resolution of the p90 ribosomal S6 kinase 2 C
      terminal kinase domain revealed a C-terminal autoinhibitory alphaL-helix that was
      embedded in the kinase scaffold and determines the inactive kinase conformation.
      We suggest a mechanism of activation through displacement of the alphaL-helix and
      rearrangement of the conserved residue Glu500, as well as the reorganization of
      the T-loop into the active conformation.

PMID- 18084306
TI  - Distinct binding modes specify the recognition of methylated histones H3K4 and
      H4K20 by JMJD2A-tudor.
AB  - The lysine demethylase JMJD2A has the unique property of binding trimethylated
      peptides from two different histone sequences (H3K4me3 and H4K20me3) through its
      tudor domains. Here we show using X-ray crystallography and calorimetry that
      H3K4me3 and H4K20me3, which are recognized with similar affinities by JMJD2A,
      adopt radically different binding modes, to the extent that we were able to
      design single point mutations in JMJD2A that inhibited the recognition of H3K4me3
      but not H4K20me3 and vice versa.

PMID- 18084307
TI  - Subunit organization and functional transitions in Ci-VSP.
AB  - Voltage-sensing domains (VSDs) confer voltage dependence on effector domains of
      membrane proteins. Ion channels use four VSDs to control a gate in the pore
      domain, but in the recently discovered phosphatase Ci-VSP, the number of subunits
      has been unknown. Using single-molecule microscopy to count subunits and voltage
      clamp fluorometry to detect structural dynamics, we found Ci-VSP to be a monomer,
      which operates independently, but nevertheless undergoes multiple voltage
      dependent conformational transitions.

PMID- 18084308
TI  - Genome-wide association in bipolar.

PMID- 18084310
TI  - The immune response against dying tumor cells: avoid disaster, achieve cure.

PMID- 18084311
TI  - Sildenafil reduces alcohol-induced gastric damage: just say 'NO'.
AB  - Although sildenafil (Viagra) and other phosphodiesterase V (PDE V) inhibitors are
      increasingly recognized for their use in the treatment of male erectile
      dysfunction and perhaps more recently pulmonary artery hypertension, less is
      known of their potential beneficial effects in other situations. Medeiros et al.,
      in the current issue of the British Journal of Pharmacology, report that
      sildenafil dramatically reduces alcohol-induced gastric damage in rats. The
      authors provide convincing evidence that such protection not only occurs via the
      nitric oxide (NO)/cGMP pathway, but also involves regulation of ATP-sensitive
      potassium channels. Therefore, in addition to exerting anti-impotence efficacy,
      PDE V inhibitors may provide significant beneficial effects from mucosal injury
      induced by alcohol.

PMID- 18084312
TI  - Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: rank
      efficacy of enzymes associated with bradykinin-mediated angioedema.
AB  - BACKGROUND AND PURPOSE: Inhibition of bradykinin metabolizing enzymes (BMEs) can
      cause acute angioedema, as demonstrated in a recent clinical trial in patients
      administered the antihypertensive, omapatrilat. However, the relative
      contribution of specific BMEs to this effect is unclear and confounded by the
      lack of a predictive pre-clinical model of angioedema. EXPERIMENTAL APPROACH:
      Rats were instrumented to record blood pressure and heart rate; inhibitors were
      infused for 35 min and bradykinin was infused during the last 5 min to elicit
      hypotension, as a functional marker of circulating bradykinin and relative
      angioedema risk. KEY RESULTS: In the presence of omapatrilat bradykinin produced
      dose-dependent hypotension, an effect abolished by B(2) blockade. In the presence
      of lisinopril (ACE inhibitor), but not candoxatril (NEP inhibitor) or apstatin
      (APP inhibitor), bradykinin also elicited hypotension. Lisinopril-mediated
      hypotension was unchanged with concomitant blockade of NEP or NEP/DPPIV
      (candoxatril+A-899301). However, hypotension was enhanced upon concomitant
      blockade of APP and further intensified in the presence of NEP inhibition to
      values not different from omapatrilat alone. CONCLUSIONS AND IMPLICATIONS: We
      demonstrated that bradykinin is degraded in vivo with an enzyme rank-efficacy of
      ACE>APP>>NEP or DPPIV. These results suggest the effects of omapatrilat are
      mediated by inhibition of three BMEs, ACE/APP/NEP. However, dual inhibition of
      ACE/NEP or ACE/NEP/DPPIV elicits no increased risk of angioedema compared to ACE
      inhibition alone. Thus, novel BME inhibitors must display no activity against APP
      to avoid angioedema risk due to high prevalence of ACE inhibitor therapy in
      patients with diabetes and cardiovascular disease.

PMID- 18084313
TI  - Role of complement C5a in mechanical inflammatory hypernociception: potential use
      of C5a receptor antagonists to control inflammatory pain.
AB  - BACKGROUND AND PURPOSE: C5a, a complement activation product, exhibits a broad
      spectrum of inflammatory activities particularly neutrophil chemoattraction.
      Herein, the role of C5a in the genesis of inflammatory hypernociception was
      investigated in rats and mice using the specific C5a receptor antagonist PMX53
      (AcF-[OP(D-Cha)WR]). EXPERIMENTAL APPROACH: Mechanical hypernociception was
      evaluated with a modification of the Randall-Selitto test in rats and electronic
      pressure meter paw test in mice. Cytokines were measured by ELISA and neutrophil
      migration was determined by myeloperoxidase activity. KEY RESULTS: Local
      pretreatment of rats with PMX53 (60-180 microg per paw) inhibited zymosan-,
      carrageenan-, lipopolysaccharide (LPS)- and antigen-induced hypernociception.
      These effects were associated with C5a receptor blockade since PMX53 also
      inhibited the hypernociception induced by zymosan-activated serum and C5a but not
      by the direct-acting hypernociceptive mediators, prostaglandin E(2) and dopamine.
      Underlying the C5a hypernociceptive mechanisms, PMX53 did not alter the cytokine
      release induced by inflammatory stimuli. However, PMX53 inhibited cytokine
      induced hypernociception. PMX53 also inhibited the recruitment of neutrophils
      induced by zymosan but not by carrageenan or LPS, indicating an involvement of
      neutrophils in the hypernociceptive effect of C5a. Furthermore, the C5a-induced
      hypernociception was reduced in neutrophil-depleted rats. Extending these
      findings in rats, blocking C5a receptors also reduced zymosan-induced joint
      hypernociception in mice. CONCLUSIONS AND IMPLICATIONS: These results suggest
      that C5a is an important inflammatory hypernociceptive mediator, acting by a
      mechanism independent of hypernociceptive cytokine release, but dependent on the
      presence of neutrophils. Therefore, we suggest that inhibiting the action of C5a
      has therapeutic potential in the control of inflammatory pain.

PMID- 18084314
TI  - Synergistic depression of NMDA receptor-mediated transmission by ketamine,
      ketoprofen and L-NAME combinations in neonatal rat spinal cords in vitro.
AB  - BACKGROUND AND PURPOSE: Spinal N-methyl-D-aspartate (NMDA)
      receptor/cyclooxygenase (COX) and nitric oxide synthase (NOS) pathways play a
      major role in nociceptive processing, and influencing them simultaneously may
      induce synergistic analgesia. This study determined the spinal antinociceptive
      interactions between ketamine (NMDA receptor channel blocker), ketoprofen (COX
      inhibitor) and L-NAME (NOS inhibitor) combinations. EXPERIMENTAL APPROACH: Using
      an in vitro neonatal rat spinal cord preparation, two A-fibre-mediated reflexes,
      the monosynaptic reflex (MSR) and the low-intensity excitatory postsynaptic
      potential (epsp), and one C-fibre-mediated reflex, the high-intensity epsp, were
      evoked electrically. The effect of drugs and drug combinations on these reflexes
      was assessed and the type of interaction determined by isobolographic analysis.
      KEY RESULTS: Infusion of ketamine alone decreased all three reflexes. That of
      ketoprofen decreased both the low and the high-intensity epsp only. Infusion of L
      NAME alone produced no significant effects. Co-infusion of fixed ratios of IC(40)
      fractions of both (ketamine+ketoprofen) and (ketamine+L-NAME) were synergistic
      for depressing the low and the high-intensity epsps. The interaction was sub
      additive for both combinations on the MSR. The only significant effect for the
      (ketoprofen+L-NAME) combination was synergism on the high-intensity epsp.
      CONCLUSIONS AND IMPLICATIONS: All three combinations synergistically depressed
      nociceptive spinal transmission, and both ketamine and ketoprofen and ketamine
      and L-NAME combinations did so with potentially decreased motor side effects. If
      such combination profiles also occur in vivo, the present findings raise the
      possibility of ultimate therapeutic exploitation of increased analgesia with
      fewer side effects.

PMID- 18084315
TI  - Endothelial alpha1-adrenoceptors regulate neo-angiogenesis.
AB  - BACKGROUND AND PURPOSE: Intact endothelium plays a pivotal role in post-ischaemic
      angiogenesis. It is a phenomenon finely tuned by activation and inhibition of
      several endothelial receptors. The presence of alpha(1)-adrenoceptors on the
      endothelium suggests that these receptors may participate in regenerative
      phenomena by regulating the responses of endothelial cells involved in neo
      angiogenesis. EXPERIMENTAL APPROACH: We evaluated the expression of the subtypes
      of the alpha(1)-adrenoceptor in isolated endothelial cells harvested from Wistar
      Kyoto (WKY) rats. We explored the possibility these alpha(1)-adrenoceptors may
      influence the pro-angiogenic phenotype of endothelial cells in vitro. In vivo, we
      used a model of hindlimb ischaemia in WKY rats, to assess the effects of alpha(1)
      adrenoceptor agonist or antagonist on angiogenesis in the ischaemic hindlimb by
      laser Doppler blood flow measurements, digital angiographies, hindlimb perfusion
      with dyed beads and histological evaluation. KEY RESULTS: In vitro,
      pharmacological antagonism of alpha(1)-adrenoceptors in endothelial cells from
      WKY rats by doxazosin enhanced, while stimulation of these adrenoceptors with
      phenylephrine, inhibited endothelial cell proliferation and DNA synthesis, ERK
      and retinoblastoma protein (Rb) phosphorylation, cell migration and tubule
      formation. In vivo, we found increased alpha(1)-adrenoceptor density in the
      ischaemic hindlimb, compared to non-ischaemic hindlimb, suggesting an enhanced
      alpha(1)-adrenoceptor tone in the ischaemic tissue. Treatment with doxazosin
      (0.06 mg kg(-1) day(-1) for 14 days) did not alter systemic blood pressure but
      enhanced neo-angiogenesis in the ischaemic hindlimb, as measured by all our
      assays. CONCLUSIONS: Our findings support the hypothesis that the alpha(1)
      adrenoceptors in endothelial cells provide a negative regulation of angiogenesis.

PMID- 18084316
TI  - Celecoxib modulates adhesion of HT29 colon cancer cells to vascular endothelial
      cells by inhibiting ICAM-1 and VCAM-1 expression.
AB  - BACKGROUND AND PURPOSE: Cyclooxygenase-2 (COX-2) is highly expressed during
      inflammation and can promote the progression of colorectal cancer. Interactions
      between cancer cells and vascular endothelial cells are key events in this
      process. Recently, the selective COX-2 inhibitor, celecoxib, was shown to inhibit
      expression of the adhesion molecules, ICAM-1 and VCAM-1, in the human colon
      cancer cell line HT29 and to inhibit adhesion of HT29 cells to FCS-coated plastic
      wells. Here, we evaluated the effects of celecoxib on adhesion of HT29 cells to
      human umbilical vein endothelial cells (HUVEC), mediated by ICAM-1 and VCAM-1, to
      assess further the potential protective effects of celecoxib on cancer
      development. EXPERIMENTAL APPROACH: Celecoxib was incubated for 4 h with HT29
      cells and HUVEC and adhesion was quantified by a computerized micro-imaging
      system. Expression analysis of ICAM-1 and VCAM-1 cell adhesion molecules was
      performed by western blot. KEY RESULTS: Celecoxib (1 nM-10 microM) inhibited,
      with the same potency, adhesion of HT29 cells to resting HUVEC or to HUVEC
      stimulated by tumour necrosis factor-alpha (TNF-alpha), mimicking inflammatory
      conditions. Analysis of ICAM-1 and VCAM-1 expression showed that celecoxib
      inhibited expression of both molecules in TNF-alpha-stimulated HUVEC, but not in
      resting HUVEC; inhibition was concentration-dependent and maximal (about 50%) at
      10 microM celecoxib. CONCLUSIONS AND IMPLICATIONS: In conclusion, our data show
      that celecoxib inhibits HT29 cell adhesion to HUVEC and expression of ICAM-1 and
      VCAM-1, in stimulated endothelial cells. These effects may contribute to the
      chemopreventive activity of celecoxib in the development of colorectal cancer.

PMID- 18084318
TI  - Celecoxib decreases expression of the adhesion molecules ICAM-1 and VCAM-1 in a
      colon cancer cell line (HT29).
AB  - BACKGROUND AND PURPOSE: We investigated the ability of celecoxib, a selective
      cyclooxygenase-2 (COX-2) inhibitor, to modulate expression of ICAM-1 and VCAM-1
      in the colon cancer cell line HT29. EXPERIMENTAL APPROACH: We analysed the effect
      of celecoxib on ICAM-1 and VCAM-1 protein and mRNA expression in HT29 cells.
      Experiments were performed in the presence of mitogen-activated protein kinases
      (MAPK) inhibitors to evaluate the involvement of these kinases in this
      phenomenon. We evaluated adhesion of HT29 cells to FCS-coated plastic wells in
      the presence of celecoxib or MAPK inhibitors. Furthermore, we studied the effect
      of celecoxib on apoptosis. KEY RESULTS: Celecoxib down-regulated ICAM-1 and VCAM
      1 expression in HT29 cells in a time- and dose-dependent way. Celecoxib reduced
      activation of p38 and p55 c-Jun terminal NH(2) kinase (JNK) MAPKs, but did not
      affect p46 JNK or p42/44 MAPK phosphorylation. Pretreatment with SB202190 or
      SP600125, specific inhibitors of p38 and JNK MAPKs, respectively, reduced ICAM-1
      and VCAM-1 expression in HT29 cells dose-dependently. Adhesion of HT29 cells to
      FCS-coated plastic wells was inhibited dose-dependently by celecoxib, and also by
      SB202190 and SP600125. Celecoxib showed a pro-apoptotic effect, inducing Bax and
      BID but down-regulating Bcl-2. CONCLUSIONS AND IMPLICATIONS: Our findings show
      that celecoxib caused down-regulation of ICAM-1 and VCAM-1, affecting the
      adhesive properties of HT29 cells in a COX-2 independent way, inhibiting p38 and
      p55 MAPKs and activating a pro-apoptotic pathway.

PMID- 18084317
TI  - Potassium channels in the regulation of pulmonary artery smooth muscle cell
      proliferation and apoptosis: pharmacotherapeutic implications.
AB  - Maintaining the proper balance between cell apoptosis and proliferation is
      required for normal tissue homeostasis; when this balance is disrupted, disease
      such as pulmonary arterial hypertension (PAH) can result. Activity of K(+)
      channels plays a major role in regulating the pulmonary artery smooth muscle cell
      (PASMC) population in the pulmonary vasculature, as they are involved in cell
      apoptosis, survival and proliferation. PASMCs from PAH patients demonstrate many
      cellular abnormalities linked to K(+) channels, including decreased K(+) current,
      downregulated expression of various K(+) channels, and inhibited apoptosis. K(+)
      is the major intracellular cation, and the K(+) current is a major determinant of
      cell volume. Apoptotic volume decrease (AVD), an early hallmark and prerequisite
      of programmed cell death, is characterized by K(+) and Cl(-) efflux. In addition
      to its role in AVD, cytosolic K(+) can be inhibitory toward endogenous caspases
      and nucleases and can suppress mitochondrial cytochrome c release. In PASMC, K(+)
      channel activation accelerates AVD and enhances apoptosis, while K(+) channel
      inhibition decelerates AVD and inhibits apoptosis. Finally, inhibition of K(+)
      channels, by increasing cytosolic [Ca(2+)] as a result of membrane depolarization
      mediated opening of voltage-dependent Ca(2+) channels, leads to PASMC contraction
      and proliferation. The goals of this review are twofold: (1) to elucidate the
      role of K(+) ions and K(+) channels in the proliferation and apoptosis of PASMC,
      with an emphasis on abnormal cell growth in human and animal models of PAH, and
      (2) to elaborate upon the targeting of K(+) flux pathways for pharmacological
      treatment of pulmonary vascular disease.

PMID- 18084320
TI  - A new fusion gene NUP98-IQCG identified in an acute T-lymphoid/myeloid leukemia
      with a t(3;11)(q29q13;p15)del(3)(q29) translocation.
AB  - NUP98 has been involved in multiple recurrent chromosome rearrangements in
      leukemia. We identified a novel fusion between NUP98 and IQ motif containing G
      (IQCG) gene from a de novo acute T-lymphoid/myeloid leukemia harboring
      t(3;11)(q29q13;p15)del(3)(q29). IQCG has two putative coiled-coil domains and one
      IQ domain. The FG repeat from NUP98 and the coiled-coil domain from IQCG were
      retained in the fusion protein. We demonstrated that NUP98-IQCG could form
      homodimer, heterodimerize with NUP98 or IQCG, bind co-activators and/or co
      repressors, and show transcriptional activity in vitro. Expression of NUP98-IQCG
      inhibited 32Dcl3 cell apoptosis induced by Ara-C, and partially blocked
      granulocyte differentiation induced by G-CSF. Colony-forming assay and serial
      replating assays indicated that NUP98-IQCG was able to stimulate proliferation,
      partially block differentiation of hematopoietic stem/progenitor cells but was
      unable to confer transformation alone. Taken together, our data indicate that
      newly identified NUP98-IQCG fusion protein may play an essential role in
      leukemogenesis, but by itself may not be sufficient to induce leukemia.

PMID- 18084319
TI  - Phosphodiesterase-4 blunts inotropism and arrhythmias but not sinoatrial
      tachycardia of (-)-adrenaline mediated through mouse cardiac beta(1)
      adrenoceptors.
AB  - BACKGROUND AND PURPOSE: beta(1) and beta(2)-adrenoceptors coexist in murine heart
      but beta(2)-adrenoceptor-mediated effects have not been detected in atrial and
      ventricular tissues, possibly due to marked phosphodiesterase (PDE) activity. We
      investigated the influence of the PDE3 inhibitor cilostamide and PDE4 inhibitor
      rolipram on the effects of (-)-adrenaline in three regions of murine heart.
      EXPERIMENTAL APPROACH: (-)-Adrenaline-evoked cardiostimulation was compared on
      sinoatrial beating rate, left atrial and right ventricular contractile force in
      isolated tissues from 129SvxC57B1/6 cross mice. Ventricular arrhythmic
      contractions were also assessed. KEY RESULTS: Both rolipram (1 microM) and
      cilostamide (300 nM) caused transient sinoatrial tachycardia but neither enhanced
      the chronotropic potency of (-)-adrenaline. Rolipram potentiated 19-fold (left
      atrium) and 7-fold (right ventricle) the inotropic effects of (-)-adrenaline. (-)
      Adrenaline elicited concentration-dependent ventricular arrhythmias that were
      potentiated by rolipram. All effects of (-)-adrenaline were antagonized by the
      beta(1)-adrenoceptor-selective antagonist CGP20712A (300 nM). Cilostamide (300
      nM) did not increase the chronotropic and inotropic potencies of (-)-adrenaline,
      but administered jointly with rolipram in the presence of CGP20712A, uncovered
      left atrial inotropic effects of (-)-adrenaline that were prevented by the
      beta(2)-adrenoceptor-selective antagonist ICI118551. CONCLUSIONS AND
      IMPLICATIONS: PDE4 blunts the beta(1)-adrenoceptor-mediated effects of (-)
      adrenaline in left atrium and right ventricle but not in sinoatrial node. Both
      PDE3 and PDE4 reduce basal sinoatrial rate in a compartment distinct from the
      beta(1)-adrenoceptor compartment. PDE3 and PDE4, acting in concert, prevent left
      atrial beta(2)-adrenoceptor-mediated inotropy. PDE4 partially protects the right
      ventricle against (-)-adrenaline-evoked arrhythmias.

PMID- 18084321
TI  - A PARP-1/JNK1 cascade participates in the synergistic apoptotic effect of
      TNFalpha and all-trans retinoic acid in APL cells.
AB  - When administrated by isolated limb perfusion, tumor necrosis factor alpha
      (TNFalpha) is an efficient antitumor agent that improves drug penetration and
      destroys angiogenic vessels. Moreover, the pronounced potentiation of TNFalpha
      induced apoptosis by NF-kappaB inhibitors suggest that these compounds could
      enhance TNFalpha antitumor efficacy through direct induction of tumor cell
      apoptosis. Therefore, attempts at amplifying signaling pathways that mediate
      TNFalpha antitumor effects could help to design combination therapies improving
      its efficiency. We report that nanomolar concentrations of all-trans retinoic
      acid (ATRA) amplify TNFalpha-induced apoptosis in APL cells expressing a specific
      repressor of NF-kappaB activation. This effect is abolished by the pan-caspase
      inhibitor, Z-VAD-fmk and by caspase-8 and -9 inhibitors. Cell death is
      accompanied by a drop of mitochondrial potential and by poly (ADP-ribose)
      polymerase (PARP) activation. Using specific PARP-1 inhibitors and siRNAs, we
      show that PARP-1 is essential for the synergistic apoptotic effect and c-Jun N
      terminal kinase 1 (JNK1) activation triggered by the ATRA/TNFalpha combination.
      JNK1 siRNAs reduce ATRA/TNFalpha-induced apoptosis, mitochondrial release of
      cytochrome c and caspase-9 activation. Altogether, these results identify a novel
      mechanism of PARP-1-induced apoptosis, in which JNK1 provides a link between PARP
      1 activation and mitochondrial pathway of caspase-9 activation. This study also
      suggests that inclusion of nanomolar doses of ATRA could be clinically beneficial
      in amplifying TNFalpha-induced antitumor signals.

PMID- 18084322
TI  - Expression of the tumour suppressor gene CADM1 is associated with favourable
      outcome and inhibits cell survival in neuroblastoma.
AB  - Cell adhesion molecule 1 (CADM1) is a putative tumour suppressor gene, which is
      downregulated in many solid tumours. In neuroblastoma, loss of CADM1 expression
      has recently been found in disseminated tumours with adverse outcome, prompting
      us to investigate its role in neuroblastoma tumour progression. Oligonucleotide
      microarray analysis of 251 neuroblastoma specimens demonstrated that CADM1
      downregulation is associated with unfavourable prognostic markers like
      disseminated stage 4, age >18 months, MYCN amplification and chromosome 11q
      alterations (P<0.001 each). Furthermore, low CADM1 expression was significantly
      correlated with unfavourable gene expression-based classification (P<0.001) and
      adverse patient outcome (P<0.001). Bisulphite sequencing and genetic analysis of
      18 primary neuroblastomas suggested that neither haploinsufficiency nor
      hypermethylation is regularly involved in CADM1 gene silencing in neuroblastoma,
      which is in contrast to results obtained in other malignancies. In addition, no
      mutations disrupting the CADM1 reading frame were found in 25 primary
      neuroblastomas. Over-expression of CADM1 in neuroblastoma cells resulted in
      significant reduction of proliferation, viability and colony formation in soft
      agar. Collectively, our results suggest that downregulation of CADM1 tumour
      suppressor gene expression is a critical event in neuroblastoma pathogenesis
      resulting in tumour progression and unfavourable patient outcome.

PMID- 18084323
TI  - ZIP kinase plays a crucial role in androgen receptor-mediated transcription.
AB  - The androgen receptor (AR) is a ligand-dependent transcription factor that plays
      a crucial role in the development and homeostasis of the prostate and in prostate
      cancer. The transcriptional activity of AR is mediated by interaction with
      multiple co-activators, which serve in chromatin modification or remodeling, or
      provide a link between specific and general transcription factors. We have
      identified zipper interacting protein (ZIP) kinase as a novel transcriptional co
      activator of the AR. ZIP kinase enhanced expression of AR-responsive
      promotor/luciferase reporter constructs in a hormone- and kinase-dependent
      manner. Similar results were obtained for glucocorticoid receptor but not for
      progesterone receptor and estrogen receptor. Following hormone treatment, AR and
      ZIP kinase formed physical complexes and associated with the promoter and
      enhancer of the prostate-specific antigen gene, as revealed by chromatin
      immunoprecipitation. Strikingly, depletion of ZIP kinase by siRNA led to
      significant reduction of AR-mediated transactivation. The interaction of ZIP
      kinase with AR seems to be mediated in part by apoptosis antagonizing
      transcription factor and in part by direct binding. Interestingly, AR was not
      phosphorylated by ZIP kinase in vitro, suggesting that it phosphorylates other co
      activators or chromatin proteins.

PMID- 18084324
TI  - Cdc7 kinase mediates Claspin phosphorylation in DNA replication checkpoint.
AB  - Cdc7 kinase is evolutionarily conserved and is involved in initiation and
      progression of DNA replication. However, roles of Cdc7 in checkpoint responses
      remain largely unknown. In this study, we show that deletion of the Cdc7 genes in
      mouse embryonic stem (ES) cells abrogates hydroxyurea (HU)- or UV-induced
      activation of Chk1. HU-induced Chk1 activation is also impaired in human cancer
      cell lines in which Cdc7 is depleted by siRNA, and Cdc7-depleted cells are more
      sensitive to HU treatment. In contrast, ATR and Rad17 are relocated to chromatin
      in these cells following HU treatment, indicating that stalled DNA replication
      forks are detected normally. Cdc7-depleted cells exhibit defects in chromatin
      association and phosphorylation of Claspin, suggesting that Cdc7 exerts its
      effect at least partially through Claspin. Consistent with this prediction, Cdc7
      interacts with and phosphorylates Claspin. We propose that Cdc7 is required for
      activation of the ATR-Chk1 checkpoint pathway through regulation of Claspin.

PMID- 18084325
TI  - Array painting reveals a high frequency of balanced translocations in breast
      cancer cell lines that break in cancer-relevant genes.
AB  - Chromosome translocations in the common epithelial cancers are abundant, yet
      little is known about them. They have been thought to be almost all unbalanced
      and therefore dismissed as mostly mediating tumour suppressor loss. We present a
      comprehensive analysis by array painting of the chromosome translocations of
      breast cancer cell lines HCC1806, HCC1187 and ZR-75-30. In array painting,
      chromosomes are isolated by flow cytometry, amplified and hybridized to DNA
      microarrays. A total of 200 breakpoints were identified and all were mapped to 1
      Mb resolution on bacterial artificial chromosome (BAC) arrays, then 40 selected
      breakpoints, including all balanced breakpoints, were further mapped on tiling
      path BAC arrays or to around 2 kb resolution using oligonucleotide arrays. Many
      more of the translocations were balanced at 1 Mb resolution than expected, either
      reciprocal (eight in total) or balanced for at least one participating chromosome
      (19 paired breakpoints). Second, many of the breakpoints were at genes that are
      plausible targets of oncogenic translocation, including balanced breaks at CTCF,
      EP300/p300 and FOXP4. Two gene fusions were demonstrated, TAX1BP1-AHCY and RIF1
      PKD1L1. Our results support the idea that chromosome rearrangements may play an
      important role in common epithelial cancers such as breast cancer.

PMID- 18084326
TI  - The EWS/FLI1 oncogenic transcription factor deregulates GLI1.
AB  - Ewing family tumors (EFT), classically Ewing's sarcoma and peripheral primitive
      neuroectodermal tumor, share a common class of tumor-specific fusion genes
      thought to be key mediators of tumor biology. Here we demonstrate that the most
      common Ewing's fusion, EWS/FLI1, produces transcriptional upregulation of GLI1
      and its direct transcriptional target PATCHED1 in a model transformation system.
      This deregulation of GLI1 is common to other EWS/ets chimera and depends on the
      functional transcriptional regulatory domains. Inhibition of GLI1 via RNAi or via
      overexpression of endogenous inhibitors results in a reduction of EWS/FLI1
      transformation activity. Activation of GLI1 appears to occur in a Hedgehog
      independent fashion as blockade of Hedgehog signaling has only a modest effect on
      EFT cells. We present evidence that EWS/FLI1 upregulation of cMYC may play a role
      in the upregulation of GLI1 in EWS/FLI1-transformed NIH3T3 cells. Finally, we
      demonstrate that observations made in a model transformation system translate to
      an Ewing cellular background. EFT cell lines express GLI1 and PATCHED and this
      expression is EWS/FLI1 dependent. Inhibition of GLI1 expression via RNAi results
      in reduced anchorage-independent growth in an EFT cell line. GLI1 appears to be a
      transcriptionally deregulated target of EWS/FLI1 that mediates a portion of its
      tumorigenic phenotype.

PMID- 18084327
TI  - Enhancement of radiation response in p53-deficient cancer cells by the Aurora-B
      kinase inhibitor AZD1152.
AB  - Overexpression of the Aurora-B kinase correlates with oncogenic transformation
      and poor prognosis. We evaluated the effects of the bona fide Aurora-B kinase
      inhibitor AZD1152 on tumor responses to ionizing radiation (IR). When p53(wt)
      HCT116 and A549 cells were pretreated with AZD1152-HQPA prior to IR, additive
      effects were observed. Interestingly, more pronounced tumoricidal effects were
      observed in p53-deficient HCT116 and HT29 cells, as well as A549 cells treated
      with the p53 inhibitor cyclic pifithrin-alpha. In vivo studies on xenografted
      mice confirmed enhanced tumor growth delay after the combination of IR plus
      AZD1152-IR as compared to IR alone. Again, this effect was more pronounced with
      p53-/- HCT116 and p53-mutant xenografts. The AZD1152-mediated radiosensitization
      was mimicked by knockdown of Aurora-B with a short interference RNA or by
      inhibition of Aurora-B by transfection with an inducible kinase-dead Aurora-B.
      The radiosensitizing effect of AZD1152 was lost in CHK2-/- and 14-3-3-/- HCT116
      cells. Altogether, these data indicate that AZD1152 can radiosensitize tumor cell
      lines in vitro and in vivo, the fact that these effects are exacerbated in p53
      deficient cancer cells is of potential interest for further clinical development.

PMID- 18084328
TI  - Oncogene-induced replication stress preferentially targets common fragile sites
      in preneoplastic lesions. A genome-wide study.
AB  - Common fragile sites (CFSs) are regions of the genome prone to breakage by
      replication inhibitors (extrinsic replication stress). Recently, we and others
      observed that oncogene-induced replication stress (RS) induces DNA damage from
      the earliest stages of cancer. Our aim was to perform a genome-wide analysis in
      precancerous and cancerous experimental models to examine whether allelic
      imbalance occurs within CFSs. Subsequently, CFSs sequence characteristics were
      assessed. We used a growth-factor-induced human skin hyperplasia and a H-ras
      induced mouse hyperplastic urothelium as preneoplastic models, along with an
      inducible U2OS-CDT1(Tet-ON) cancer cell line model, all bearing established
      oncogene-induced RS stimuli. Human DNA was analysed with Affymetrix SNP
      microarrays, while mouse DNA was analysed with Nimblegen array CGH. We studied 56
      aphidicolin-type CFSs and 1914 regions of control, nonfragile DNA. Our
      theoretical in silico analysis spanned 2.16 billion nonoverlapping bases on human
      chromosomes 1-22. Our results provide direct experimental evidence indicating
      that genomic alterations were more common within CFSs in epidermal and urothelial
      preneoplastic lesions as well as in cancer. CFSs were on average less flexible
      than nonfragile regions, contained more guanine-cytosine (GC) and Alu sequences.
      Importantly, regions with loss-of-heterozygosity were also less flexible and had
      a higher Alu percentage.

PMID- 18084329
TI  - Suppression of cFLIP is sufficient to sensitize human melanoma cells to TRAIL-
      and CD95L-mediated apoptosis.
AB  - Death ligands such as tumor necrosis factor (TNF)-related apoptosis-inducing
      ligand (TRAIL) and certain forms of CD95L are attractive therapeutic options for
      metastatic melanoma. Since knowledge about the regulation of death receptor
      sensitivity in melanoma is sparse, we have analysed these signaling pathways in
      detail. The loss of CD95 or TRAIL-R1, but not of TRAIL-R2, surface expression
      correlated with apoptosis sensitivity in a panel of melanoma cell lines. In
      contrast, the expression of proteins of the apical apoptosis signaling cascade
      (FADD, initiator caspases-8 and cFLIP) did not predict apoptosis sensitivity.
      Since both TRAIL-R1 and -R2 transmit apoptotic signals, we asked whether cFLIP,
      highly expressed in several of the cell lines tested, is sufficient to maintain
      resistance to TRAIL-R2-mediated apoptosis. Downregulation of cFLIP in TRAIL-R2
      positive, TRAIL-resistant IGR cells dramatically increased TRAIL sensitivity.
      Conversely ectopic expression of cFLIP in TRAIL-sensitive, TRAIL-R2-expressing
      RPM-EP melanoma cells inhibited TRAIL- and CD95L-mediated cell death. Thus,
      modulation of cFLIP is sufficient to sensitize TRAIL-R2-expressing cells for
      TRAIL. Taken together, albeit expressing all proteins necessary for death
      receptor-mediated apoptosis, TRAIL-R1 negative melanoma cells cannot undergo
      TRAIL- or CD95L-induced apoptosis due to expression of cFLIP. Hence, cFLIP
      represents an attractive therapeutic target for melanoma treatment, especially in
      combination with TRAIL receptor agonists.

PMID- 18084330
TI  - Cyclin D3 action in androgen receptor regulation and prostate cancer.
AB  - Prostate cancer (PCa) cell proliferation is dependent on activation of the
      androgen receptor (AR), a ligand-dependent transcription factor. AR activation
      controls G1-S phase progression through fostering enhanced translation of the D
      type cyclins, which promote cell cycle progression through activation of CDK4/6.
      However, the D-type cyclins harbor additional, CDK4/6 kinase-independent,
      functions through manipulation of transcription factors, including AR. It was
      previously established that cyclins D1 and D3 have the potential to modulate AR,
      and with regard to cyclin D1, disruption of this function occurs in human tumors.
      Therefore, it was essential to interrogate cyclin D3 function in this tumor type.
      Here, we show that cyclin D3 is found in association with AR in PCa cells, as
      mediated through a conserved motif. Cyclin D3 functions to attenuate AR activity
      through defined mechanisms that include modulation of ligand-dependent
      conformational changes and modulation of chromatin binding activity. Accumulated
      cyclin D3 slows cell proliferation in AR-dependent cells, thus suggesting that
      androgen-induced D-type cyclin production serves to temper the mitogenic response
      to androgen. Supporting this hypothesis, it is shown that cyclin D3 expression is
      reduced in primary PCas as a function of tumor grade, and inversely correlates
      with the proliferative index. In total, these data identify cyclin D3 as a
      critical modulator of the androgen response, whose deregulation may foster
      unchecked AR activity in PCa.

PMID- 18084331
TI  - Searching for alternative hematopoietic stem cell donors for pediatric patients.
AB  - The use of alternative hematopoietic stem cell (HSC) donors has been witnessing
      important progress, mainly due to: (i) better HLA matching at the allelic level
      between donor and recipient in unrelated HSC transplantation (HSCT) translating
      into better patient outcome; (ii) better donor choice and patient selection in
      unrelated, often HLA-mismatched, cord blood transplantation and (iii) new
      strategies of adoptive cell therapy aimed at improving the results of T-cell
      depleted haploidentical HSCT from a relative. Currently, it is possible to find
      an HSC donor for virtually almost all children with an indication to receive
      allogeneic HSCT and lacking an HLA-identical sibling. Each of the three options
      of HSCT from alternative donors has advantages and limitations. Therefore, any
      physician has to carefully evaluate, for each single pediatric patient in need of
      an allograft, all the possible alternatives to choose the best HSC donor, taking
      into account type of disease to be treated, urgency of transplantation, donor
      characteristics and center's experience. This review will analyze in detail the
      advantages and limitations of each of the three options of alternative donor HSCT
      and the main criteria to be used for choosing the most suitable donor for
      pediatric patients lacking an HLA-identical sibling.

PMID- 18084332
TI  - Hematopoietic stem cell transplantation in childhood inherited bone marrow
      failure syndrome.
AB  - Aplastic anemia is a rare disease in children that is most commonly idiopathic
      and less often a hereditary disorder. Hereditary bone marrow failure (BMF)
      syndromes, however, should be considered both in children and in adults before
      any attempt at treatment. Precise diagnosis is important because it will modify
      prognostic treatment options and the results of bone marrow transplantation. In
      this review, we will report recent results of treatment of Fanconi anemia and
      other hereditary BMF syndromes.

PMID- 18084333
TI  - Pharmacokinetics of oral mycophenolate mofetil in combination with CsA in dogs
      after nonmyeloablative allogeneic hematopoietic stem cell transplantation.
AB  - Mycophenolate mofetil (MMF) has been used successfully in solid organ
      transplantation (SOT) and more recently in nonmyeloablative hematopoietic stem
      cell transplantation (HSCT) for prophylaxis of graft rejection and acute graft
      versus-host disease. However, the pharmacokinetics of MMF seem to differ when
      applied in HSCT compared to SOT. Here, we analyzed pharmacokinetics of
      mycophenolic acid (MPA), the active metabolite of MMF, in a nonmyeloablative
      canine HSCT model. Dogs received nonmyeloablative TBI for conditioning followed
      by leukocyte antigen-identical littermate HSCT and immunosuppression containing
      cyclosporin A (CsA) and different doses of MMF. Pharmacokinetics were performed
      on days 2, 14 and 27. Dose escalation of MMF from 10 to 30 mg/kg tended to
      increase area under the curve (AUC) and the apparent oral clearance by 45 and
      110%, respectively. Doses applied had no linear association with MPA
      concentration or blood trough level. No significant drug accumulation occurred
      over time. Using a twice daily MMF regimen, we conclude that an AUC of 30-60
      mug/ml h as recommended for SOT cannot be reached in HSCT. Toxicities did not
      permit single doses higher than 30 mg/kg. Thus, if larger AUCs are desired in
      order to assure sufficient immunosuppression in HSCT, MMF might have to be
      administered at least three times daily.

PMID- 18084334
TI  - The EBMT activity survey 2006 on hematopoietic stem cell transplantation: focus
      on the use of cord blood products.
AB  - This report describes the hematopoietic stem cell transplantation (HSCT) activity
      in Europe in 2006 by indication, donor type and stem cell source. It illustrates
      differences compared to previous years and concentrates on the use of cord blood
      transplants. In 2006, there were 25 050 first HSCT, 9661 allogeneic (39%), 15 389
      autologous (61%) and 3690 additional re- or multiple transplants reported from
      605 centers in 43 participating countries. Main indications were leukemias (7963
      (32%; 85% allogeneic)); lymphomas (14 169 (56%; 89% autologous)); solid tumors
      (1564 (6%; 95% autologous)); non-malignant disorders (1242 (5%; 90% allogeneic))
      and non-classified 'others' (112 (1%)). There was an increase in allogeneic HSCT
      of 9% when compared to 2005, while autologous HSCT numbers remained similar.
      There were 544 allogeneic cord blood HSCT, which corresponds to 5% of all
      allogeneic HSCT. The majority, 67%, were used for patients with leukemia. The
      highest percentage of cord blood transplants, 27%, was seen for inherited
      disorders of metabolism. No autologous cord blood transplants were reported. The
      highest increase in allogeneic HSCT was observed for AML, which comprises 31% of
      all allogeneic HSCT. Numbers of autologous HSCT remained similar in most main
      indications. This data provide an update of the current HSCT experience in
      Europe.

PMID- 18084335
TI  - Long-term outcomes of adults with acute lymphoblastic leukemia after autologous
      or unrelated donor bone marrow transplantation: a comparative analysis by the
      National Marrow Donor Program and Center for International Blood and Marrow
      Transplant Research.
AB  - For adults with high-risk or recurrent ALL who lack a suitable sibling donor, the
      decision between autologous (Auto) and unrelated donor (URD) hematopoietic stem
      cell transplantation (HSCT) is difficult due to variable risks of relapse and
      treatment-related mortality (TRM). We analysed data from two transplant
      registries to determine outcomes between Auto and URD HSCT for 260 adult ALL
      patients in first (CR1) or second (CR2) CR. All patients received a myeloablative
      conditioning regimen. The median follow-up was 77 (range 12-170) months. TRM at 1
      year post transplant was significantly higher with URD HSCT; however, there were
      minimal differences in TRM according to disease status. Relapse was higher with
      Auto HSCT and was increased in patients transplanted in CR2. Five-year leukemia
      free (37 vs 39%) and overall survival (OS) rates (38 vs 39%) were similar for
      Auto HSCT vs URD HSCT in CR1. There were trends favoring URD HSCT in CR2. The
      long-term follow-up in this analysis demonstrated that either Auto or URD HSCT
      could result in long-term leukaemia-free survival and OS for adult ALL patients.
      The optimal time (CR1 vs CR2) and technique to perform HSCT remains an important
      clinical question for adult ALL patients.

PMID- 18084336
TI  - Emergency double unrelated umbilical cord blood transplant for acute
      lymphoblastic leukemia after very late deferral of bone marrow donor.

PMID- 18084337
TI  - Stem cell transplantation for pediatric lymphoma: past, present and future.
AB  - Lymphoma is the third most common cancer in children < or =15 years of age. The
      prognosis for children with newly diagnosed chemosensitive non-Hodgkin's lymphoma
      (NHL) and Hodgkin's disease (HD) has improved significantly. However, in children
      with relapsed and refractory NHL, the prognosis is not as promising and the best
      treatment approach for this poor risk group continues to be a challenge. Between
      25 and 30% of patients with advanced stage HD still relapse and in subsets of
      this group, the outcome is dismal. Aggressive chemotherapy followed by autologous
      bone marrow transplantation has been used with some improvement in survival. Some
      centers have investigated allogeneic stem cell transplantation in pediatric
      patients with recurrent/relapsed lymphoma. There is little consistency in
      therapeutic approaches and there is no formal recommendation on the best approach
      for this poor prognostic subgroup. We illustrate the reported pediatric
      experience of transplantation for lymphoma and discuss how the results from these
      trials are influencing how we approach the treatment in certain subgroups of
      pediatric patients with relapsed/refractory lymphoma.

PMID- 18084338
TI  - Safe administration of oral BU twice daily during conditioning for stem cell
      transplantation in a paediatric population: a comparative study between the
      standard 4-dose and a 2-dose regimen.
AB  - We compared outcome and toxicity in two paediatric groups undergoing SCT and
      treated with busulphan (BU) by the oral route of administration. One group
      receiving the standard dose of 1 mg/kg q.i.d. for a total of 16 doses was
      compared with age- and disease-matched patients receiving 2 mg/kg of BU b.i.d.
      for a total of eight doses. Seventy-two patients from two Swedish paediatric
      transplantation centres were included; one centre used a standard q.i.d.
      administration (n=37) and the second centre used a b.i.d. administration setting
      (n=35). Our primary objective was to determine the incidence of veno-occlusive
      disease (VOD), graft-versus-host disease (GVHD), relapse frequency and transplant
      related mortality in both cohorts. A total of 17 autologous and 55 allogeneic
      transplantations was performed for malignant (n=47) and non-malignant (n=25)
      diseases in the two centres during the period 1990-2005. No significant
      difference in the incidence of VOD, graft rejection, GVHD, relapse rate or
      overall survival was observed between the two centres. The clinical outcome of
      SCT for paediatric patients conditioned with oral BU at a dose of 2 mg/kg for
      eight doses is comparable to that found for children conditioned using the
      standard regimen given 1 mg/kg q.i.d. for 16 doses.

PMID- 18084339
TI  - Unrelated cord blood transplantation for severe combined immunodeficiency and
      other primary immunodeficiencies.
AB  - HCT is currently the treatment of choice for children with severe primary
      immunodeficiencies (PIDs). Frequently, these patients lack an HLA-identical
      sibling donor, and umbilical cord blood (UCB) transplantation may be an option;
      however, experience in this field remains scant. Fifteen children with PID (SCID
      11, X-linked lymphoproliferative syndrome 2, Omenn's syndrome 1, Wiskott-Aldrich
      syndrome 1) received a UCB transplant. The donor was unrelated in 14 cases and
      related in 1. Median age at transplant was 11.6 months (range, 2.9-68.0) and
      median weight 7 kg (range, 4-21). Thirteen patients were conditioned with
      busulphan and cyclophosphamide and 2 with fludarabine and melphalan. Nine
      patients received antithymocyte globulin. Median NC x 10(7)/kg infused was 7.9
      (range, 2.9-25.0) and median CD34 x 10(5)/kg 2.9 (range, 1.0-7.9). All patients
      engrafted. Median days to >0.5 x 10(9)/l neutrophils was 31. Eight patients
      developed acute graft-versus-host disease (GvHD) grades II-IV and one chronic
      GvHD. Viral and fungal infections were frequent. Four patients died: three from
      GvHD grade IV complicated by infection and one from progressive interstitial lung
      disease. Five-year survival was 0.73+/-0.12. All surviving patients presented
      complete immunologic reconstitution. No patient is intravenous immunoglobulin
      (IVIg) replacement therapy-dependent. UCB transplantation is a valid option for
      children with PID who lack an HLA-identical sibling donor.

PMID- 18084340
TI  - Allogeneic hematopoietic cell transplantation for metastatic breast cancer.
AB  - We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to
      describe the efficacy of allogeneic hematopoietic cell transplantation (HCT).
      Median follow-up for survivors was 40 months (range, 3-64). A total of 39
      patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning
      (RIC) regimens. More patients in the RIC group had poor pretransplant performance
      status (63 vs 26%, P=0.002). RIC group developed less chronic GVHD (8 vs 36% at 1
      year, P=0.003). Treatment-related mortality rates were lower with RIC (7 vs 29%
      at 100 days, P=0.03). A total of 9 of 33 patients (27%) who underwent immune
      manipulation for persistent or progressive disease had disease control,
      suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1
      year was 23% with myeloablative conditioning and 8% with RIC (P=0.09). Women who
      developed acute GVHD after an RIC regimen had lower risks of relapse or
      progression than those who did not (relative risk, 3.05: P=0.03), consistent with
      a GVT effect, but this did not affect PFS. These findings support the need for
      preclinical and clinical studies that facilitate targeted adoptive immunotherapy
      for breast cancer to explore the benefit of a GVT effect in breast cancer.

PMID- 18084341
TI  - Vancomycin-resistant enterococcal colonization appears associated with increased
      mortality among allogeneic hematopoietic stem cell transplant recipients.
AB  - There are no cohort studies describing outcomes of patients colonized with
      vancomycin-resistant enterococci (VRE) undergoing allogeneic hematopoietic stem
      cell transplantation (AHSCT). We therefore conducted a retrospective cohort study
      of 217 consecutive adults undergoing AHSCT at the Mayo Clinic (Rochester, MN,
      USA) from 1998 to 2004. We analyzed the association between VRE colonization
      prior to transplant and 100-day post transplant mortality and morbidity. We
      identified 22 pretransplant VRE colonized patients and 195 non-colonized
      patients. Both groups had similar baseline characteristics with the following six
      exceptions. Colonized patients were more likely to have had pretransplant
      Clostridium difficile-associated diarrhea, pretransplant acute renal failure,
      AML, Cy/TBI conditioning, decreased platelet count at time of transplantation and
      myeloablative conditioning regimens. Overall, patients colonized with VRE were
      twice as likely to die by day 100 post transplant compared to non-colonized
      patients (hazard ratio: 2.1, P=0.028). This association persisted even after
      adjusting for differences in baseline characteristics. Increased mortality in the
      colonized group correlated with the presence of VRE bacteremia. Overall,
      pretransplant VRE colonization appears to be an independent risk factor for
      increased mortality post-AHSCT.

PMID- 18084342
TI  - Resistance to thyroid hormone: one of several defects causing reduced sensitivity
      to thyroid hormone.

PMID- 18084343
TI  - New therapeutic approaches to treat medullary thyroid carcinoma.
AB  - Medullary thyroid carcinoma (MTC) accounts for up to 8% of all thyroid cancers.
      Although primary surgery is curative in the vast majority of patients treated at
      an early stage, disease can persist or recur with deleterious effects on quality
      of life. Local and distant metastases can occur and are the major causes of
      mortality. Reoperation, embolization, and perhaps radiotherapy can improve the
      outcome for some patients who are not cured by primary surgery, but there is a
      need for novel treatments. No comprehensive clinical trial data are available on
      conventional cytotoxic agents for the treatment of MTC. Patients with distant
      metastases, in particular, might benefit from several novel compounds directed
      against angiogenesis and molecular targets in tumor cells, such as products of
      the proto-oncogene RET and mutants of it, and other signaling components. Well
      conducted clinical trials are needed to assess and optimize these treatment
      strategies, and this article outlines how such trials should be conducted.
      Although RET mutations are common in hereditary MTC and can occur in some cases
      of sporadic MTC, knowledge of other molecular defects associated with the
      development of MTC should reveal new targets for therapy.

PMID- 18084344
TI  - Antagonists of growth-hormone-releasing hormone: an emerging new therapy for
      cancer.
AB  - This article reviews the potential clinical uses of antagonists of growth-hormone
      releasing hormone (GHRH) for tumor therapy. GHRH antagonists suppress the growth
      of various human cancer lines xenografted into nude mice; such tumors include
      breast, ovarian, endometrial and prostate cancers, lung cancers (small-cell lung
      carcinomas and non-small-cell lung carcinomas), renal, pancreatic, gastric and
      colorectal carcinomas, brain tumors (malignant gliomas), osteogenic sarcomas and
      non-Hodgkin's lymphomas. The antitumor effects of GHRH antagonists are exerted in
      part indirectly through the inhibition of the secretion of GH from the pituitary
      and the resulting reduction in the levels of hepatic insulin-like growth factor I
      (IGF-I). The main effects of the GHRH antagonists are, however, exerted directly
      on tumors. GHRH ligand is present in various human cancers and might function as
      an autocrine and/or paracrine growth factor. Pituitary-type GHRH receptors and
      their splice variants are also found in many human cancers. The inhibitory
      effects of GHRH antagonists seem to be due to the blockade of action of tumoral
      GHRH. Antagonists of GHRH can also suppress cancer growth by blocking production
      of IGF-I and/or IGF-II by the tumor. Further development of GHRH antagonists that
      are still-more potent should lead to potential therapeutic agents for various
      cancers.

PMID- 18084345
TI  - Drug Insight: eplerenone, a mineralocorticoid-receptor antagonist.
AB  - Increasing recognition of the role of aldosterone in cardiovascular disease has
      been supported by a significant body of evidence from animal models. This
      evidence has been translated into clinical practice, and large-scale, randomized,
      placebo-controlled trials have confirmed the beneficial effects of
      mineralocorticoid blockade in patients with heart failure. As a consequence,
      there has been a resurgence in the use of mineralocorticoid-receptor antagonists
      in clinical practice that has prompted the search for a potent and specific
      antagonist without the sexual side effects of spironolactone. Eplerenone, a
      mineralocorticoid-receptor antagonist with minimal binding to the progesterone
      and androgen receptors, is now licensed for treatment of heart failure in Europe
      and heart failure and hypertension in the US; it has also been proposed as a
      treatment for a variety of cardiovascular conditions. This article reviews the
      current concepts of the actions of aldosterone at a cellular level. Recent
      findings regarding its role as a cardiovascular hormone, both in animal models
      and human studies, are discussed. We also describe the development of
      mineralocorticoid-receptor blockers following the isolation of aldosterone and
      discuss the subsequent search for a specific mineralocorticoid antagonist. In
      addition we detail the effects of eplerenone in a number of clinical situations
      and outline its potential future applications.

PMID- 18084346
TI  - Familial isolated primary hyperparathyroidism caused by mutations of the MEN1
      gene.
AB  - BACKGROUND: Familial isolated primary hyperparathyroidism (FIHP) is an autosomal
      dominant disorder that can represent an early stage of either the multiple
      endocrine neoplasia type 1 (MEN1) or hyperparathyroidism-jaw tumor (HPT-JT)
      syndromes; alternatively, the condition can be caused by an allelic variant of
      MEN1 or HRPT2 (hyperparathyroidism 2 gene), or caused by a distinct entity
      involving another locus. We have explored these possibilities in a patient with
      primary hyperparathyroidism, whose mother had a history of renal calculi and
      primary hyperparathyroidism. INVESTIGATIONS: Serum biochemistry and radiological
      investigations for primary hyperparathyroidism, MEN1 and HPT-JT, and genetic
      testing for MEN1 and HRPT2 mutations were undertaken. DIAGNOSIS: FIHP with
      primary hyperparathyroidism as the sole endocrinopathy due to a previously
      unreported heterozygous missense germline MEN1 mutation, Tyr351Asn. In addition,
      another unreported heterozygous missense germline MEN1 mutation, Trp220Leu, was
      identified in an unrelated male patient with FIHP, whose mother and sister also
      had primary hyperparathyroidism. DNA from a parathyroid tumor from the sister
      revealed a loss of heterozygosity in which the mutant allele was retained. This
      is consistent with Knudson's 'two-hit' model of hereditary cancer and a tumor
      suppressor role for MEN1 in FIHP. MANAGEMENT: The patient underwent
      parathyroidectomy and has remained normocalcemic over a follow-up period of 6
      years. The other four patients have remained normocalcemic for a follow-up period
      of 4-15 years following parathyroidectomy. None has developed abnormalities of
      the MEN1 syndrome, providing further support that FIHP is a distinct genetic
      variant of the MEN1 syndrome.

PMID- 18084347
TI  - [Is hygiene likely to guide those who want to live "in full health"?].

PMID- 18084348
TI  - [Impact and state of the art of regional healthcare planning and management
      guidelines in a local health authority of the Lazio region (Italy)].
AB  - The aim of this study was to evaluate the impact of health care planning and
      management guidelines, elaborated by the Lazio regional healthcare authority, on
      the organizational structure and operational processes of local health
      authorities and, more specifically, of the Roma C local health authority. The
      guidelines are made up of three volumes and mainly describe an operational model,
      rather than being a set of standard references aimed at standardizing the quality
      of information low systems in local healthcare authorities. The guidelines are
      essentially a didactic text, and were elaborated by a consulting firm,
      Engineering Management Consulting, on behalf of the Lazio regional authority. In
      the first section, the main concepts are defined, while in subsequent sections,
      detailed models regarding the specific subject matter are described. Although the
      guidelines represent a useful tool in the process of converting local health
      authorities of the Lazio region into "business" organizations, so far they have
      been of use only in the first phase of assessment of different organizational
      models for healthcare planning and management. There is still a long way ahead
      towards defining standard procedures and references for describing activities and
      costs. This is what should hopefully be achieved briefly and which will
      necessarily require the introduction of a data warehouse and business
      intelligence software that will allow monitoring of activities and making short
      term predictions through the use balanced scorecards and data mining.

PMID- 18084349
TI  - [Evidence-based public health: strategies aimed at increasing adherence to
      colorectal cancer screening programs].
AB  - The ministerial decree 29/11/2001 included colorectal carcinoma screening
      procedures among the "essential" health care services that should be delivered
      free of charge to citizens. Secondary prevention programs for colorectal cancer
      must therefore be implemented in all Italian regions. An international literature
      search on colorectal cancer screening was performed in order to provide a
      resource for public health workers and decision makers, for selecting
      interventions to improve adherence to screening programs. The following
      interventions have been proven to be effective: reducing structural barriers to
      screening, active recall systems, multicomponent interventions involving active
      recall and health education, active reminder systems, periodic dissemination of
      results, and physician health education. Opportunistic screening by general
      practitioners, that is, performing faecal occult blood testing in asymptomatic
      patients consulting a GP for other reasons, is a strategy should also be
      implemented.

PMID- 18084350
TI  - [Multicentric study to evaluate the quality of discharge abstract coding of
      admissions in which the treatment was not performed and to identify a possible
      appropriateness indicator].
AB  - The aim of this study was to assess the quality of discharge abstract data
      regarding admissions in which the planned treatment was not performed, in 4
      hospitals in the Rome metropolitan area. The main objective was to evaluate the
      appropriateness of admissions through use of the Italian version of the
      Appropriateness Evaluation Protocol (AEP/PRUO). Inconsistencies between discharge
      abstract forms and hospital records were found in 95/142 (66,9%) of examined
      records. These were subsequently evaluated through the Appropriateness Evaluation
      Protocol and overall , 95,6% of inconsistent records were found to be
      inappropriate admissions. Monitoring V64 codes may represent an indirect
      indicator of appropriateness.

PMID- 18084351
TI  - The prevalence of latent tuberculosis infection in social marginal groups. An
      experience conducted in Tuscany.
AB  - Tuberculosis is encountering a renewal attention due to emergent causes, linked
      primarily to migration from high-endemic countries of many subjects who present
      important risk factors as poverty, homelessness, drug abuse, HIV infection. The
      purpose of the present study is to evaluate the spread of Mycobacterium
      tuberculosis in social groups traditionally at higher risk of developing the
      disease and often difficult to detect. Tuberculin screening with Mantoux
      intradermal reaction has been carried out on 2014 subjects with one or more risk
      conditions. We have considered the following risk conditions: extra European
      community (e-EC), immigrants, nomads, drug dependants, immunodeficients, alcohol
      dependants, prison inmates living in protected community or home, subjects known
      to have contact with a TB case with also one or more of the above conditions. A
      logistic-regression model has been applied to evaluate the association between
      several social and/or pathological risk factors and Mantoux responsiveness. The
      population groups examined show higher rates than the Italian population. The
      majority of risk factors have a significant association (positive or negative)
      with Mantoux positivity. In particular, if we add to the condition of e-EC (coded
      as reference category) other conditions (community, contact, prison), the
      probability of positive Mantoux increases. In fact, the OR values are 2.92 (C.I.
      95%=2.23-3.82) for "e-EC migrants + protected communities", 2.35 (C.I. 95%=1.62
      3.40) for "e-EC migrants + contact" and 2.53 (C.I. 95%=1.24-5.14) for "e-EC
      migrants + prison". On the other hand the condition of "e-EC migrants + nomad"
      appears to be significantly "protective" in relation to Mantoux positivity
      (OR=0.23; C.I. 95%=0.16-0.33), and the same is true for "protected community +
      contact", "prison", "drug dependence", "drug dependence + immunodeficiency" with
      respective OR values of 0.37 (C.I. 95%=0.15-0.93), 0.29 (C.I. 95%=0.14-0.58),
      0.20 (C.I. 95%=0.14-0.28) and 0.12 (C.I. 95%=0.04-0.41). There is a sharp
      difference between those socially organized and those without social reference,
      who seek occasional and temporary hospitality in available structures.

PMID- 18084352
TI  - [Designating hospitals according to levels of care: theoretical aspects and
      problems].
AB  - The progressive evolution of health care systems in terms of organization and
      delivery of care has given body to the development of a new hospital model
      oriented toward providing global patient care and formulated into different
      levels of care. The authors discuss several organizational and professional
      aspects which should be developed in order to fully implement this model giving
      special emphasis to the development of definitions of levels of care and of new
      models of medical and nursing care.

PMID- 18084353
TI  - [Infection control in the outpatient setting].
AB  - Data regarding the observance of infection control practices in ambulatory
      healthcare settings is scarce. This type of data is important since the health
      care system has evolved in such a way that hospital stays are now briefer and
      there is an increased provision of healthcare in outpatient settings, such as day
      surgery, day hospital and ambulatory care services. Studies have shown that
      transmission of infectious diseases in outpatient health care settings is often
      associated with lack of, or insufficient adherence to, evidence-based preventive
      measures. Outpatients have less risk factors for nosocomial infections than
      inpatients, nevertheless, some high risk settings include physicians' waiting
      rooms (airborne and droplet transmission) and outpatient settings in which
      invasive procedures are performed. Preventive strategies consist in verifying the
      adherence to infection control guidelines (this should be done by specifically
      trained personnel), developing disinfection and sterilization protocols for
      medical devices (that are comparable to those used in hospitals), training of
      healthcare personnel, and development of efficacy-based infection control
      protocols for outpatient settings.

PMID- 18084354
TI  - [Chikungunya: a new epidemy for Europe. Is there a new vaccine coming soon?].
AB  - Chikungunya virus is known to cause large epidemics in Indian Ocean islands and
      countries, but it has recently been detected in autochthonous cases in Ravenna,
      Central Italy. After transmission through infected mosquitoes, an influenza like
      illness occurs. It is generally a benign disease and no specific therapy is
      available; the only prevention consists in avoiding mosquito bites. Due to the
      recent autochthonous transmission in an industrialized country the research for a
      sure and effective vaccine is restarting.

PMID- 18084355
TI  - [The stone child from Innset].

PMID- 18084356
TI  - [In mass media's spotlight].

PMID- 18084357
TI  - [Was Yersinia pestis the cause of the black death?].

PMID- 18084358
TI  - [Life after heart transplantation].

PMID- 18084359
TI  - [Self-assessed health and psychological symptoms after heart transplantation].
AB  - BACKGROUND: The purpose of this study was to assess quality of life (QoL, self
      reported health) and psychological adjustment in a sample of heart transplanted
      patients. MATERIAL AND METHODS: The sample comprised 147 (117 men) Norwegian
      heart transplanted patients (operated 1983 - 1999). Data on QoL and psychological
      adjustment were collected during annual routine follow-up controls between 1998
      and 2000. The Short Form 36 (SF-36), the Symptom Checklist 90-Revised (SCL-90-R),
      and Beck Depression Inventory (BDI) were used. RESULTS: On average, heart
      transplant recipients reported significantly reduced QoL and increased levels of
      psychological symptoms compared to a normative population. Recently operated
      patients reported a generally good QoL compared to the norms, while there was a
      worsening after 3 years of both the patients' psychological symptoms and QoL,
      compared to patients who were transplanted less than 3 years ago. The clinical
      significance was underscored by the BDI; 30 % of the patients were classified as
      suffering from mild depression (BDI >/= 10) if transplanted more than 3 years
      ago, compared to 16 % in patients operated less than 3 years ago (p < .05). 62 %
      of the patients never returned to work and became/remained permanent disability
      pensioners. INTERPRETATION: This study demonstrates that heart transplanted
      patients have a reduced QoL and psychological problems after the transplantation
      and this seems to worsen with time. Detection and early intervention of
      psychological symptoms may assist heart transplant survivors in their return to
      everyday life. The cross-sectional nature of the study makes it difficult to
      infer causality from these results.

PMID- 18084360
TI  - [Chlamydia trachomatis infection in central Norway--testing patterns and
      prevalence].
AB  - BACKGROUND: CHLAMYDIA TRACHOMATIS: is the most prevalent sexually transmitted
      bacterial disease in Norway. The purpose of the present study was to describe
      testing patterns and prevalence of Chlamydia in a Norwegian county, with special
      focus on urine-based testing. : MATERIAL AND METHODS: Data on all Chlamydia tests
      1990 - 2006 for men and women 15 - 59 years old, living in Sor-Trondelag County,
      were retrieved from a laboratory database. 243 671 Chlamydia test results were
      eligible for analysis. RESULTS: Testing rates were considerably higher for men
      than for women in all age-groups throughout the study period. Urine-based testing
      was introduced for men in 2001 and for women in 2004. In 2006, urine-based
      testing comprised most of the test volume for men (15 - 19 year-olds: 87.9 %, 20 
      24 year-olds: 81.7 %), but far less for women (15 - 19 year-olds: 55.8 %, 20 -
      24 year-olds: 26.5 %). The proportion of positive tests was higher for women with
      a urine-based test than for those with a sample from the cervix (2006: 15 - 19
      year-olds: 18.0 % versus 13.5 %, 20 - 24 year-olds: 16.9 % versus 9.6 %).
      INTERPRETATION: Male testing rates have increased after urine-based testing for
      Chlamydia became an option. Young women delivering urine samples are more often
      positive than women with cervix samples.

PMID- 18084361
TI  - [Postcoital contraception or abortion? A longitudinal study of young women].
AB  - BACKGROUND: The use of postcoital contraception or emergency contraception has
      increased in many countries. This has been linked to an expected reduction in the
      abortion rates, but so far there is no evidence of such an association. A
      possible explanation could be that women who are in the risk zone for abortion
      typically do not use emergency contraception. The aim of study was to investigate
      possible differences between the two groups. MATERIAL AND METHODS: 768 Norwegian
      women (a representative sample) were followed up from they were 15 to 27 years.
      Data were collected through surveys on; emergency contraception and induced
      abortion, sociodemographic characteristics, family relationships, and individual
      aspects previously reported to be associated with an increased risk of induced
      abortion (education level, conduct problems and depression). RESULTS: Women who
      use emergency prevention are recruited (more often than expected) from families
      with a high income (OR 2.0; 95 % CI 1.3 - 2.9), but otherwise have no
      characteristics that discriminate them from the rest of the population. Induced
      abortion was however associated with risk factors such as depression (OR 3.2; 95
      % CI 1.7 - 6.0) and deviant peer groups (OR 2.5; 95 % CI 1.3 - 4.8), and they
      rarely have education at a university- or college level (OR 0.2; 95 % CI 0.1 -
      0.7). INTERPRETATION: Emergency contraception appears to be used by others than
      those with typical risk factors for abortion. One should consider targeted
      preventive interventions to increase the use of emergency contraception in groups
      at-risk for induced abortion.

PMID- 18084362
TI  - [Bechterew disease--a consensus on diagnosis and treatment].
AB  - BACKGROUND: New treatment alternatives have improved the prospects for patients
      with ankylosing spondylitis. MATERIAL AND METHODS: Experts from 10 countries
      developed and voted for 9 questions regarding diagnostics, monitoring and
      pharmacological treatment (except biological) of ankylosing spondylitis. The
      Norwegian group added two questions on non-pharmacological treatment. A thorough
      literature search was performed. 39 experts attended a Norwegian consensus
      meeting where they developed and voted for the final recommendations for
      treatment of ankylosing spondylitis. RESULTS: Statements are generally based on
      limited evidence, but are highly supported by the experts. Important diagnostic
      factors are persistent inflammatory back pain in individuals under 40 years, HLA
      B27-tissue, effect of NSAIDs, peripheral arthritis, morning stiffness and
      elevated acute phase reactants. MRI of sacroiliac joints is important for early
      diagnosis, but abnormalities must be verified by conventional radiographs. Long
      term follow-up should include measures of inflammation, pain and function. NSAIDs
      and local corticosteroids are first line drugs for treatment of enthesitis.
      NSAIDs/coxibs are recommended as flexible on-demand-regimens. Patients should be
      encouraged to adapt exercising to disease severity and individual needs.
      INTERPRETATION: Consensus-based processes among experts may give valuable
      contributions to the management of ankylosing spondylitis.

PMID- 18084363
TI  - [Leisure-time physical activity in the Norwegian county Nordland].
AB  - BACKGROUND: A more sedentary way of life and less physical activity has increased
      the risk of many common health problems. This implicates a need for knowledge
      about activity patterns and determinants for physical activity in Norway.
      MATERIAL AND METHOD: 2914/6836 (43 %), 1499 women and 1415 men (18 - 69 years),
      responded to a questionnaire survey performed in the county of Nordland in 2002.
      The total physical activity was estimated from the question "How active are you?"
      for 22 different leisure time activities. Activity was expressed in number of
      Metabolic Equivalent hours per week (METh/week) and as the sum of METh/week.
      Leisure-time activity was related to age, sex, health and level of education of
      the respondents. RESULT AND INTERPRETATION: Backcountry hiking and outdoor life
      comprise a large part of the physical activities undertaken by adults in
      Nordland. Women are slightly less physically active than men. The median
      METh/week was 21.7 for women and 24.7 for men. Physical activity decreases
      slightly with age for both women and men. The correlation between self-rated
      health and physical activity is positive, and dependence of the level of
      education shows an overall positive trend. The results from this survey emphasize
      the need for standardized Norwegian questionnaires about physical activity and an
      agreed method of measuring physical activity.

PMID- 18084364
TI  - [Fruit and berries--interactions with drugs].
AB  - Diet is one of many factors that could alter the pharmacokinetics of drugs.
      Several fruits and berries have recently been shown to contain agents that affect
      drug-metabolizing enzymes. Grapefruit is the most well-known example, but also
      Sevillian orange, pomelo and star fruit contain agents that inhibit cytochrome
      P450 3A4 (CYP3A4), which is the most important enzyme in drug metabolism. The
      present article reviews published information on potential interactions between
      drugs and fruits/berries, with main focus on inhibition and induction of
      metabolizing enzymes.

PMID- 18084365
TI  - [Media which harm and kill].

PMID- 18084366
TI  - [Heavy burdens and complex disease--an integrated perspective].
AB  - Complex chronic diseases require an increasing proportion of society's resources
      and represent a growing challenge. Valid biomedical models of etiology,
      pathogenesis, treatment and prognosis are inadequate for understanding these
      diseases. The article discusses current knowledge about the impact of stress on
      the immune-, hormonal - and central nervous systems, and integrates this
      knowledge with a phenomenological understanding of the body in an attempt to
      explain the complex chronic fatigue syndrome. The medical significance of the
      individual's biography is highlighted, and the inadequacy of statistically
      grounded biomedical research when aiming to understand complex disease is
      presented. By regarding human beings as persons who experience bodily and who
      both create and convey meaning, we claim to have transgressed the mind-body
      dichotomy in complex disease development. The dichotomy converges in the living
      body.

PMID- 18084367
TI  - [Genital Chlamydia--can we rely on the figures?].

PMID- 18084368
TI  - [End of life at intensive care units].

PMID- 18084369
TI  - [Weak report about antidepressive agents from the Knowledge Center].

PMID- 18084370
TI  - [Deficiency of cornea transplant donors].

PMID- 18084371
TI  - [End of opioid addicts' dancing around?].

PMID- 18084372
TI  - [More poetic physicians].

PMID- 18084373
TI  - [Diagnosis and control of colorectal cancer].

PMID- 18084374
TI  - [No effect of recommended treatment of acute back pain].

PMID- 18084375
TI  - [Costly non-coverage by travel health insurance].

PMID- 18084377
TI  - [CT colonography in the screening for polyps and cancer].

PMID- 18084380
TI  - [Pesta is coming].

PMID- 18084381
TI  - [Bladder stone surgery in antiquity].
AB  - Bladder stone with subsequent urinary retention was a common and challenging
      disease up to the 19 th century, and still is in tropical countries. Surgery has
      been used to remove stones (lithotomy) or to break them into small pieces
      (lithotripsy) since antiquity. If surgery was impossible, the urinary retention
      could be relieved with a catheter. The surgical technique for bladder stone
      remained unchanged up to the 16 th century, and some of its principles are still
      employed in urology. This article translates parts of Aulus Cornelius Celsus'
      treatise on bladder stone, found in his encyclopedia "De Medicina". The text is
      compared with archaeological findings from Pompeii.

PMID- 18084382
TI  - [A pregnancy of 10-years duration].
AB  - In January 1813 the peasant woman Randi Jonsdatter from Kvikne in Hedmark had
      been pregnant for 10 years. One day she slipped in her cattle-shed, and soon
      after "gave birth" to the remains of a decomposed stone child (lithopaedion)
      through an incision above her navel. The woman, who was about 50 years old, lived
      for many years after the "birth". This is the earliest known Norwegian case of a
      lithopaedion, a dead calcified fetus from an extra uterine pregnancy. The case is
      documented in a letter written only three months after the event. This letter is
      now archived in The Norwegian National Library's Manuscript Collection. The case
      was also published by the physician Christian Stengel at the Roros mines, in the
      medical periodical EYR: in 1827. Stone children occur very rarely. Only two other
      cases, from 1858 and 1885, are known in Norway.

PMID- 18084383
TI  - [La donna e mobile--the hysteria diagnosis in Norway in the 19th century].
AB  - The last half of the 19 th century has been described as "the golden age of
      hysteria". Hysteria was a frequently used diagnosis in this period and received
      increasing attention from a number of prominent medical researchers, such as Jean
      Martin Charcot and Sigmund Freud in Europe and for example Edvard Bull, Paul
      Winge and Ragnar Vogt in Norway. It also appears in Norwegian fiction by the
      contemporary writers Henrik Ibsen, Bjornstjerne Bjornson and Amalie Skram. We can
      thus speak of an exchange between medicine and culture, and of hysteria as a
      cultural diagnosis that reflects its time. The symptoms are described as
      comprehensive, and several different etiological models can be traced. Even
      though hysteria is not exclusively associated with the female body and psyche, it
      is constructed at the interface of scientific opinion and notions of femininity.

PMID- 18084384
TI  - [The health of sailors--at sea and in port towns].
AB  - Initiatives to promote better health among Norwegian sailors in the period 1890 -
      1940 should be seen in the context of contemporary Norwegian health care
      policies. Preventive measures were most important, and special attention was
      given to hygiene and tuberculosis. Public health officials, shipping companies
      and non-governmental organizations, such as the Norwegian Red Cross, cooperated
      to do this work. Health care work among mariners had some special aspects.
      Sailors were the first group in the country to be subject to obligatory health
      checks. The sailors were exposed to other diseases in ports abroad than at home;
      and during the period examined in this article, Norwegian tropical medicine and
      ships medicine were interwoven. In addition, the prevention and treatment of
      venereal diseases among sailors were subject to great interest, especially after
      the First World War. The article is based on the author's research for her
      doctoral dissertation, i.e. literature and historical sources, such as articles
      from journals and newspapers and archival resources (from the Ministry of Social
      Affairs and the Shipping Office at the Ministry of Trade).

PMID- 18084385
TI  - [Vladimir Bechterew--the professor stopped by Stalin].

PMID- 18084386
TI  - [When state authorisation was introduced for medical doctors in Norway].
AB  - In 1927, a law was implemented in Norway that for the first time required medical
      students to be state authorised before they could practice medicine and use the
      title medical doctor. The question of authorisation split the professional elite,
      both the Norwegian Medical Association and the Medical Faculty at the University
      of Oslo. Those very few members of the professional elite that advocated
      authorisation did, however, convince the government as well as the parliament
      that authorisation should be given and recalled by the state. State authorisation
      was first of all aimed at protecting the medical profession against "unfit"
      members; it was not a question of monopolising medical work or preventing other
      groups from working within the healthcare services. To put this into context, one
      should know that there had been a transition from a bureaucratic to a free labour
      market and most doctors were no longer engaged by the State, but had to practise
      in a private market. One feared that this would undermine the doctors' authority
      and status. In this situation, authorisation by the state was considered
      necessary to safeguard the public's confidence in doctors and their work.

PMID- 18084387
TI  - [The complex plague--reconsiderations of an epidemic from the past].
AB  - Speculations have arisen about the black plague in recent years - was it a
      disease caused by YERSINIA PESTIS: or something else? Extensive outbreaks in
      India in the 1890s have formed the basis for descriptions of the plague, both for
      those who believe that the medieval plagues and modern plague were different
      diseases and for those who claim that the plague has been one and the same
      disease throughout history. The plague was more or less defined as a disease in
      the 1890s, and the understanding of its clinical course and dissemination at the
      time has uncritically been understood as the general model for spreading of the
      plague. But plague is a many-faceted disease. It has spread to five continents in
      modern times, through an array of ecosystems and under widely different climatic
      conditions. It can also be passed on to man, and from one individual to another,
      in different ways. The biological conditions that prevailed in India have not
      been relevant for medieval Norway. The preconditions for spreading of plague
      epidemics of the past in a Nordic climate must therefore have been different. It
      can only be expected that contemporary descriptions of historic epidemics are
      different from those in modern times.

PMID- 18084389
TI  - [Causal concepts and health conduct in Indian folk medicine].
AB  - BACKGROUND: Norway is an increasingly multicultural society, and cultural
      diversities are a challenge for doctor-patient-relationships. MATERIAL AND
      METHOD: Qualitative and quantitative studies aimed at describing health behaviour
      and causal concepts, were undertaken in a village in India in July 2003. 13
      villagers and 5 local providers of traditional health care were interviewed in a
      semi-structured way, and questionnaire-based interviews were conducted in 56 (out
      of 118) households on health behaviour. RESULTS: Three main causal concepts were
      found: balance between the qualities HEAT: and COLD: in the body, DISTHI: (evil
      eye; witchcraft) and evil spirits. Health behaviour is mainly influenced by the
      understanding of what causes disease, experience with the provider of treatment
      and the treatment itself. DISCUSSION: Causal concepts, or ways of understanding
      disease, were common to those found in similar studies. Physician awareness of
      these concepts will be helpful when communicating with patients from other
      cultural backgrounds.

PMID- 18084392
TI  - Optical torque controlled by elliptical polarization.
AB  - We show theoretically and demonstrate experimentally that highly absorbing
      particles can be trapped and manipulated in a single highly focused Gaussian
      beam. Our studies of the effects of polarized light on such particles show that
      they can be set into rotation by elliptically polarized light and that both the
      sense and the speed of their rotation can be smoothly controlled.

PMID- 18084393
TI  - Beam splitting on weak illumination.
AB  - We demonstrate, in both two and three dimensions, how a self-guided beam in a non
      Kerr medium is split into two beams on weak illumination. We also provide an
      elegant physical explanation that predicts the universal character of the
      observed phenomenon. Possible applications of our findings to guiding light with
      light are also discussed.

PMID- 18084394
TI  - Interference model for back-focal-plane displacement detection in optical
      tweezers.
AB  - The lateral position of an optically trapped object in a microscope can be
      monitored with a quadrant photodiode to within nanometers or better by
      measurement of intensity shifts in the back focal plane of the lens that is
      collimating the outgoing laser light. This detection is largely independent of
      the position of the trap in the field of view. We provide a model for the
      essential mechanism of this type of detection, giving a simple, closed-form
      analytic solution with simplifying assumptions. We identify intensity shifts as
      first-order far-field interference between the outgoing laser beam and scattered
      light from the trapped particle, where the latter is phase advanced owing to the
      Gouy phase anomaly. This interference also reflects momentum transfer to the
      particle, giving the spring constant of the trap. Our response formula is
      compared with the results of experiments.

PMID- 18084395
TI  - Reconstruction of discontinuous light-phase functions.
AB  - The reconstruction of discontinuous light-phase functions is of major importance
      in adaptive optics. An efficient and simple algorithm that can reconstruct large
      arrays of phases from phase differences is presented. We prove that the algorithm
      yields a perfect result in the absence of noise, and we describe the function
      that it maximizes. We suggest a method that makes use of the reconstructed phase
      to measure the position of branch points. A simulation of the reconstruction of a
      33x33 phase array is presented.

PMID- 18084396
TI  - Microtags with 150-nm line gratings fabricated by use of extreme-ultraviolet
      lithography.
AB  - The microtag concept is an anticounterfeiting and security measure. Microtags are
      computer-generated holograms (CGH's) consisting of 150-nm lines arranged to form
      300-nm-period gratings. The microtags that we describe were designed for readout
      at 442nm . The smallest microtag measures 56micromx80 microm when viewed at
      normal incidence. The CGH design process uses a modified iterative Fourier
      transform algorithm to create either phase-only or phase-and-amplitude microtags.
      We also report on a simple and compact readout system for recording the
      diffraction pattern formed by a microtag. The measured diffraction patterns agree
      very well with predictions.

PMID- 18084397
TI  - Do evanescent waves contribute to the far field?
AB  - Evanescent waves have become of considerable interest in recent years because of
      developments in near-field optics. Claims have been made that such waves
      contribute to the radiation fields of sources and to the far fields of
      scatterers. We show, by considering a spherical scalar wave and a linear electric
      dipole field, that these claims are misleading and that such contributions are
      without physical consequences. Our conclusions apply to a much broader class of
      fields than those considered in this Letter.

PMID- 18084398
TI  - Punctuated quadrature phase-shifting interferometry.
AB  - We describe a method and algorithm for reducing the sensitivity of phase-shifting
      interferometry to external vibrations. Using an interline-transfer camera, a
      shutter, and a fast phase shifter, we acquire a series of paired interferograms
      in quadrature, with the pairs spaced to maximize residual phase-error
      cancellation. The rapid acquisition of quadrature pairs significantly improves
      resistance of interferometry to low-frequency vibrations.

PMID- 18084399
TI  - Total reflection of waves propagating from an isotropic medium to an anisotropic
      medium.
AB  - We examine the value n(i)/n(eff)(theta(t)) , the ratio of the indices of
      refraction for waves transmitted from an isotropic medium to an anisotropic
      medium. It is found that total reflection can occur in the case of propagation
      from a rarer medium to a denser medium.

PMID- 18084400
TI  - Spectroscopy on a modulated magneto-optical trap.
AB  - We demonstrate a new type of high-resolution two-photon frequency modulation (FM)
      spectroscopy with cold atoms in a magneto-optical trap. Instead of modulating the
      probe as in ordinary FM spectroscopy, we modulate the trap itself by FM of the
      trapping beams. We present theoretical as well as experimental results for both
      absorption and polarization rotation spectroscopy. Finally, we demonstrate two
      photon FM spectroscopy, using the intrinsic phase noise of the trapping diode
      lasers.

PMID- 18084401
TI  - Efficient resonant frequency doubling of a cw Nd:YAG laser in bulk periodically
      poled KTiOPO(4).
AB  - A cw Nd:YAG laser was quasi-phase-matched frequency doubled by a bulk
      periodically poled flux-grown KTiOPO(4) crystal in an external resonant cavity.
      The conversion efficiency and the second-harmonic power with a pump of 225 mW
      were 55% and 123.5 mW, respectively. The loss of the 1-cm-long crystal, which
      operated near room temperature, was 1.3% and was dominated by scatter from the
      cleaved facets of the crystal. No damage, photorefractive or other, was observed
      at intensites of 370Wmm(-2) , but beam size had to be optimized to eliminate
      thermal-induced instabilities in the doubling cavity.

PMID- 18084402
TI  - Modulational instability of a strip beam in a bulk type I quadratic medium.
AB  - The evolution of a strip (one-dimensional) fundamental beam with propagation
      distance owing to spatial modulational instabilities was analyzed in a quadratic
      medium near type I phase matching. We obtained the gain coefficient for the
      modulational instability and showed that the wave evolves into a clean periodic
      sequence of solitary waves and does not reproduce the incident beam.

PMID- 18084403
TI  - Long-term operation of CsLiB(6)O(10) at elevated crystal temperature.
AB  - We have successfully resolved the degradation problem of CsLiB(6)O(10) (CLBO) by
      means of elevated crystal temperature. CLBO crystals were continuously operated
      at 160 degrees C in ordinary room humidity. No degradation of performance was
      observed after more than 1 month. We believe that heating CLBO crystal above 130
      degrees C can relieve stresses introduced by crystal hydration, cutting,
      polishing, and thermal shock owing to laser power absorption. Thus long-term
      operation of CLBO crystal is achieved for effective application of laser
      frequency conversion. Output stability from CLBO is also further enhanced at
      elevated crystal temperature.

PMID- 18084404
TI  - In-line Nd:YAG resonator using self-pumped phase conjugation in Cr(4+):YAG.
AB  - We report the operation of an in-line Nd:YAG resonator using self-pumped phase
      conjugation in Cr(4+): YAG at lambda=1.064microm in the nanosecond regime. The
      output beam has a high-quality diffraction-limited TEM(00) mode and a pulse shape
      of ~15ns , showing the self- Q -switching ability of the resonator. A maximum
      extraction of 18mJ and a maximum reflectivity of 2.0 are measured. A transient
      model provides insight into the energy characteristics and the dynamics of such
      an in-line resonator.

PMID- 18084405
TI  - Application of a continuously tunable, cw optical parametric oscillator for high
      resolution spectroscopy.
AB  - We report the use of a smoothly tunable, single-frequency continuous-wave optical
      parametric oscillator (OPO) for high-resolution spectroscopy. The OPO is based on
      potassium titanyl phosphate and is resonant for both signal and idler fields,
      resulting in a device with a very low pump power threshold of 30 mW. The
      frequency-selective nature of the doubly resonant oscillator ensures that the
      signal and idler modes can be tuned across the entire phase-match bandwidth
      without the need for additional intracavity frequency-selective components.
      Smooth frequency tuning of the output of the OPO is obtained by tuning of the
      pump laser. To demonstrate the practicality of our OPO we recorded the absorption
      spectrum of cesium vapor in the 1-microm spectral region.

PMID- 18084406
TI  - Multiband generation of mid infrared by use of periodically poled lithium
      niobate.
AB  - We report the generation of simultaneous multiband mid-infrared laser output by
      use of periodically polled lithium niobate pumped by the 1.54-microm output from
      a KTP optical parametric oscillator. The multiband source is capable of producing
      three mid-infrared wavelengths ranging from 2.5 to 4microm . In initial
      experiments we obtained output powers of 542 mW near 2.5microm and 453 mW near
      4microm , with power conversion efficiencies of 30% and 25%, respectively. To the
      best of our knowledge, this is the first demonstration of this kind in the
      literature.

PMID- 18084407
TI  - Optical frequency division by 3 of 532 nm in periodically poled lithium niobate
      with a double grating.
AB  - Optical frequency division by 3 of 532 nm is demonstrated by back-to-back
      difference-frequency generation in a periodically poled lithium niobate crystal
      with a double grating. The first grating generates 1596-nm light from 532- and
      798-nm inputs, and the second grating mixes the 798-nm input and the 1596-nm
      output from the first grating to produce a second 1596-nm output. The beat signal
      between the two 1596-nm outputs is detected and frequency stabilized to yield the
      3:1 frequency ratio.

PMID- 18084409
TI  - Single-mode excitation of multimode fibers with ultrashort pulses.
AB  - Single-mode excitation of step-index multimode fibers with light sources with
      short temporal coherence lengths is demonstrated. Multimode fiber designs with
      reduced microbending-induced mode coupling are described that allow the
      propagation of the fundamental mode over long lengths with negligible mode
      coupling even in the presence of tight fiber bends. At a wavelength of 1.56microm
      a fiber with a core diameter of 45microm can preserve the fundamental mode for a
      propagation length of ~20m . Such fibers allow coiling with a coil diameter as
      small as 7cm.

PMID- 18084408
TI  - Oscillatory mode coupling and electrically strobed gratings in photorefractive
      quantum-well diodes.
AB  - Oscillatory mode coupling between two coherent laser beams is produced when an
      interference pattern moves against a quasi-static electrically strobed grating in
      a photorefractive AlGaAs/GaAs multiple-quantum-well diode operated in the quantum
      confined Stark geometry. The oscillation frequency is equal to the frequency
      difference between the two laser beams and provides a method to measure high
      frequency Doppler shifts or large surface displacements for laser-based
      ultrasound. Combined photorefractive gains (normally forbidden by symmetry in the
      Stark geometry) and absorptive gains approach 1200cm(-1)during two-wave mixing
      using moving gratings.

PMID- 18084410
TI  - 8-mJ TEM(00) diode-end-pumped frequency-quadrupled Nd:YAG laser.
AB  - A frequency-quadrupled Nd:YAG laser pumped by a commercially available high
      brightness stack is described. A master oscillator power amplifier configuration
      was implanted, and the laser delivered energy of 8 mJ at 0.266microm . The laser
      was air cooled for easy use.

PMID- 18084411
TI  - Tunable carbon monoxide overtone laser sideband system for precision spectroscopy
      from 2.6 to 4.1 microm.
AB  - We report a source of tunable laser radiation for high-precision molecular
      spectroscopy in the 2.6- 4.1-microm spectral region. Laser light from a CO
      overtone laser is mixed with microwaves, generating tunable sidebands of ~1 mW of
      power. We achieve very high absolute frequency accuracy by frequency-offset
      locking the CO laser to a CO(2) laser secondary frequency standard. The
      uncertainty of the laser frequency is less than 30 kHz (Dnu/nu=3x10(-10)) , and
      the laser linewidth is of the order of 100 kHz. This tunable and ultrastable
      laser system is suitable for very accurate molecular spectroscopy and metrology
      in a most interesting wavelength region. We demonstrate an application of the
      system to saturated-absorption spectroscopy of a rovibrational transition of
      carbonyl sulfide.

PMID- 18084412
TI  - Femtosecond optical parametric oscillator based on periodically poled KTiOPO(4).
AB  - We report a femtosecond optical parametric oscillator based on a periodically
      poled KTiOPO(4) crystal for which quasi-phase matching is achieved with a 24
      microm poling period. The singly resonant parametric oscillator, synchronously
      pumped by a Ti:sapphire laser at a wavelength of 758 nm, generates a signal at
      1200 nm and an idler at 2060 nm. The maximum signal power conversion efficiency
      of the device is 22% with a pump depletion of 69%. We tune the signal wavelength
      over a 200-nm band by changing the cavity length. In addition, pump wavelength
      tuning provides output tunability in the 1000-1235-nm range.

PMID- 18084413
TI  - 27-fs extreme ultraviolet pulse generation by high-order harmonics.
AB  - Autocorrelation measurement was demonstrated for the first time to our knowledge
      in the XUV region to measure the width of a high-order harmonic pulse. Two-photon
      ionization of rare gases was used as a nonlinear process for the autocorrelation
      measurement. The 27-fs pulse width that was obtained is, to our knowledge, the
      shortest in the XUV region.

PMID- 18084414
TI  - Detection of freely propagating terahertz radiation by use of optical second
      harmonic generation.
AB  - We report the application of electric-field-induced optical second-harmonic
      generation as a new technique for measuring the field of freely propagating
      terahertz radiation. Using silicon as the nonlinear medium, we demonstrate
      subpicosecond time resolution and a sampling signal that varies linearly with the
      terahertz electric field. This approach, which is attractive for centrosymmetric
      media, permits a significantly broadened class of materials to be exploited for
      free-space sampling measurements.

PMID- 18084415
TI  - Interaction of atomic wave packets with four-wave mixing: detection of rubidium
      and potassium wave packets by coherent ultraviolet emission.
AB  - The observation of an atomic wave packet by use of a coherent, nonlinear-optical
      process is reported. Wave packets formed in K or Rb vapor by two-photon
      excitation of ns and (n-2)dstates (n=8 for K; n=11 , 12 for Rb) with red (~620
      nm) , 80-100-fs pulses were detected by four-wave mixing in pump-probe
      experiments. The temporal behavior of the wave packet is observed by monitoring
      the coherent UV radiation generated near the alkali mp(2)P? (2)S(1/2) (7</=m</=12
      for Rb; 5</=m</=7 for K) resonance transitions when a probe pulse is scattered by
      the wave packet established by the earlier (identical) pump pulse. The spatial
      and spectral characteristics of the UV emission are well described by axially
      phase-matched four-wave mixing, and all the prominent frequency components of the
      wave packets are associated with energy differences between pairs of excited
      states for which Diota=0 or Diota=2 . These results demonstrate that the wave
      packet modulates chi((3))of the medium, thus rendering the wave packet
      detectable.

PMID- 18084416
TI  - Improved development of thermally fixed holograms in photorefractive LiNbO(3)
      crystals with high-intensity laser pulses.
AB  - Holographic gratings were thermally fixed in iron-doped photorefractive LiNbO(3)
      crystals and developed with frequency-doubled Q -switched pulses of a Nd:YAG
      laser (light wavelength, 532 nm; pulse duration, 3 ns). The saturation values of
      the diffraction efficiency increased with increasing pulse light intensity.
      Compared with development with cw light, high-intensity laser pulse development
      resulted in an enlargement of the diffraction efficiency of a factor of ~2 . A
      contribution of the intrinsic defect Nb on Li site to the charge transport is
      most probably the origin of this effect. The results are useful, e.g., for
      improvements of volume holographic memories and wavelength filters.

PMID- 18084417
TI  - Exciplex liquid-phase thermometer using time-resolved laser-induced fluorescence.
AB  - Pulsed photoexcitation of hydrocarbon fuels doped with organic molecules exhibits
      a temperature-dependent fluorescence spectrum that is used as the basis for a
      weakly intrusive optical thermometer. By use of pulsed excitation from a 308-nm 8
      ns XeCl excimer laser with gated detection of the fluorescence emissions from
      doped n -heptane, we demonstrate that time-resolved measurement of the excited
      monomer and the redshifted excited-state complex (exciplex) fluorescence
      emissions can yield sub-1 degrees accuracy for temperatures ranging from 440 K to
      the vicinity of the critical temperature (540 K). The experiments also show that
      the exciplex fluorescence spectrum is pressure independent below and above
      supercritical pressure.

PMID- 18084418
TI  - Power measurement of noise-initiated Brillouin scattering in optical fibers for
      sensing applications.
AB  - We discuss the measurement of noise-initiated Brillouin scattered power in
      optical fibers and its application to distributed sensing systems. In particular,
      we consider the use of Brillouin scattering in the nonlinear regime,
      demonstrating a novel processing technique that compensates for the nonlinear
      growth of the scattered signals. The signal-to-noise ratio performance of this
      technique is evaluated, highlighting the importance of the noise contributed by
      the random statistics of the scattered field and yielding the conditions for
      optimum system operation.

PMID- 18084419
TI  - Image restoration of multiple noisy images by use of a priori knowledge of the
      anisoplanatic point-spread function.
AB  - We propose and simulate an iterative maximum-likelihood image reconstruction
      method that uses multiple images taken through the turbulent atmosphere under
      photon-limited conditions. The method assumes that the point-spread function
      corresponding to each image has been measured by a guide star or other technique.
      Although a guide star is still required, wave-front correction is achieved
      through postprocessing instead of by the mechanical methods currently used with
      adaptive optics. A restored image of greatly increased quality was found to be
      produced after only 10 iterations. Additional iterations continued to reduce the
      mean-square error.

PMID- 18084420
TI  - Alternative explanation of specular optical activity.
AB  - Bungay et al. [Phys. Lett. A 174, 335 (1993)] reported observing polarization
      plane rotation in optical reflection at normal incidence from GaAs, an effect
      that they term specular optical activity. Their preferred interpretation
      hypothesizes a partially symmetric third-rank bulk tensor arising from
      nonlocality, even though its existence would violate time reversibility. We
      present an alternative explanation based on the derived properties of a nonlocal
      surface layer that preserves time reversibility.

PMID- 18084421
TI  - Polymer-coated hollow fiber for CO(2) laser delivery.
AB  - Hollow fibers for CO(2) laser light have been fabricated with a cyclic olefin
      polymer as the inner dielectric. A film of cyclic olefin polymer was coated
      inside the glass capillary tubing by a simple liquid-flowing process. A polymer
      coated fiber with a 700-microm bore showed a loss of 0.06 dB/m for CO(2) laser
      light because cyclic olefin polymer has low absorption at a 10.6-microm
      wavelength.

PMID- 18084422
TI  - Anomalous absorption of TM electromagnetic waves by an ultrathin layer: optical
      analog of liquid friction.
AB  - A strong maximum of absorption (as much as 100%) of bulk TM electromagnetic waves
      by an ultrathin film with imaginary dielectric permittivity is shown to exist at
      some optimal film thickness. This typical thickness is usually much smaller than
      the wavelength and the wave penetration depth in the material of the film. The
      absorptivity maximum increases and the typical thickness decreases with
      increasing dielectric permittivity of the layer. An optical analog of linear
      (liquid) friction is discussed. A frictional contact approximation for TM
      electromagnetic waves is analyzed, and relevant boundary conditions with an
      optical coefficient of friction are derived.

PMID- 18084423
TI  - Two-dimensional photonic bandgap optical limiter in the visible.
AB  - Operation of a two-dimensional photonic bandgap optical limiter was studied at
      514.5 nm for pulse durations of 0.1 to 4 ms . Photonic crystals consisted of 180-
      230-nm spatial-period nanochannel glasses containing a thermal nonlinear liquid.
      A dynamic range in excess of 130 was observed in a single-element device.

PMID- 18084424
TI  - Annihilation of photorefractive solitons.
AB  - We investigate experimentally the interaction of two-dimensional solitary beams
      in photorefractive strontium barium niobate crystal. We show that simultaneous
      collision of many solitons can result in complete annihilation of some of them.
      This effect depends on the relative phases of the solitons and may be useful for
      application in the formation of multiport waveguide junctions.

PMID- 18084425
TI  - Efficient noncollinear parametric amplification of weak femtosecond pulses in the
      visible and near-infrared spectral range.
AB  - We report measurement of efficient amplification of weak femtosecond
      supercontinuum seed pulses by use of a noncollinear optical parametric process in
      BBO crystal pumped with 150-fs pulses from a frequency-doubled regenerative
      amplified Ti:sapphire laser at 390nm . The highest amplification factor, 10(8) ,
      was achieved for 3x10(-16)J energy seed pulses at wavelength of 560nm.

PMID- 18084426
TI  - Direct-to-video holographic readout in quantum wells for three-dimensional
      imaging through turbid media.
AB  - Customized photorefractive quantum-well devices have been developed for real-time
      video acquisition of coherence-gated, three-dimensional images in turbid media.
      Large-field-of-view holographic imaging with direct video capture is now
      possible. We have evaluated the role of intensity-limited device performance in
      Fourier-plane and image-plane holography in such devices and, using near-infrared
      light, have imaged through turbid phantoms of 13 mean free paths' scattering
      depth with 50-microm transverse and 60-microm depth resolution.

PMID- 18084427
TI  - All-fiber zero-insertion-loss add-drop filter for wavelength-division
      multiplexing.
AB  - We developed and fabricated an all-fiber add-drop filter by recording a Bragg
      grating in the waist of an asymmetric mode converter-coupler formed by adiabatic
      tapering and fusing of two locally dissimilar, single-mode optical fibers. The
      insertion loss of the device was ~0.1 dB .A narrow spectral bandwidth (<1 nm) and
      a large add-drop efficiency (>90%) were also demonstrated. In addition, the
      filter was polarization independent.

PMID- 18084428
TI  - Graded-index characteristics in single-crystal fibers.
AB  - Single-crystal fibers of Ti(3+):Al(2)O (3)have been grown by the laser-heated
      pedestal growth technique and shown to exhibit radial refractive-index gradients.
      A refractive-index increase of approximately 12% in the fiber core with respect
      to the fiber sidewalls has been measured. The index profile can be fitted with a
      parabolic model. Postgrowth treatment of Cr(3+):Gd(3)Sc (2)Al (3)O(12)fibers has
      been shown to produce a uniform cladding region with a graded-index core. The
      core index is some 12.5% larger than the cladding region, with an index profile
      shape that is approximately parabolic in nature.

PMID- 18084429
TI  - Modes of UV-written planar waveguides.
AB  - The UV-induced refractive-index increase in photosensitive planar waveguides is
      modeled by an exponential profile. Closed-form field solutions are given and
      dispersion curves are calculated for TE and TM modes. Modes in air-covered
      waveguides can be less sensitive to the UV-written profile than modes in buried
      waveguides.

PMID- 18084430
TI  - Noise reduction in a mode-locked semiconductor laser by coherent photon seeding.
AB  - We have used coherent photon seeding to reduce the noise in an actively mode
      locked extended-cavity semiconductor laser. Feedback is provided by an auxiliary
      cavity terminated either by a wedge plate or by a phase-conjugate mirror. Both
      conventional and phase-conjugate feedback can reduce the low-frequency noise
      components (0-5 MHz) by as much as 36 dB, hence drastically reducing the pulse
      fluctuations. A noise reduction of as much as 18 dB is also observed in the 0.01
      3.0-GHz frequency range. We obtained these results while preserving the pulse
      duration (26 ps) and improving the time-bandwidth product.

PMID- 18084431
TI  - Coherent-absorber mode locking of solid-state lasers.
AB  - We study solid-state laser mode locking in the self-induced transparency regime
      of an intracavity absorber. Depending on the absorber dephasing, pulse energy,
      and resonator dispersion, we find stable coherent 2pi -pulse operation, pulse
      splitting, oscillatory pulse shapes, and smooth transition to incoherent
      saturable-absorber mode locking.

PMID- 18084432
TI  - Anomalous long-range propagation of femtosecond laser pulses through air: moving
      focus or pulse self-guiding?
AB  - Self-guided propagation of femtosecond laser pulses is studied for a converging
      beam configuration. Channeling of the pulse energy through various gases is
      observed over distances well beyond the lens focal point, a fact that cannot be
      explained by the moving-focus model. The results are in good agreement with three
      dimensional numerical simulations.

PMID- 18084433
TI  - Stable multigigahertz pulse-train formation in a short-cavity passively harmonic
      mode-locked erbium/ytterbium fiber laser.
AB  - We demonstrate a short-cavity erbium-ytterbium fiber laser that is passively mode
      locked by a saturable Bragg reflector with a fundamental repetition rate of 235
      MHz . The laser operates in the soliton regime and under passive harmonic mode
      locking with 11 pulses in the cavity and produces output pulse trains at 2.6 GHz
      with transform-limited 270-fs pulses and 1.6 mW of average power. Within the
      cavity the multiple pulses form a stable pattern with fixed, nearly equal pulse
      to-pulse temporal spacings, causing the output pulse train to have timing offsets
      of less than 15 ps. A slow gain-recovery model is proposed to explain the pulse
      train self-organization.

PMID- 18084434
TI  - Efficient and tunable diode-pumped femtosecond Yb:glass lasers.
AB  - Diode-pumped Yb:phosphate and Yb:silicate glass lasers have been passively mode
      locked for the first time to the authors' knowledge. Reliable self-starting mode
      locking without critical cavity alignment has been achieved with intracavity
      semiconductor saturable-absorber mirrors and soliton mode locking. We generated
      pulses as short as 58 fs with the Yb:phosphate laser and 61 fs with the
      Yb:silicate laser at average output powers of 65 and 53 mW, respectively. The
      pulse repetition rate was 112 MHz. Additionally, we demonstrated tunability of
      femtosecond pulses from 1025 to 1065 nm for the Yb:phosphate and from 1030 to
      1082 nm for the Yb:silicate glasses. The highest mode-locked output power was 405
      mW, with 183-fs pulses from the phosphate glass. The diode pump power was 1.68 W,
      corresponding to 24% optical-to-optical efficiency. The highest cw output power
      was 510 mW at the same incident pump power.

PMID- 18084435
TI  - Femtosecond Cr:forsterite laser diode pumped by a double-clad fiber.
AB  - We present a compact, all-solid-state femtosecond Cr:forsterite laser. The laser
      is pumped by diodes through a double-clad fiber. Kerr-lens mode locking is
      initiated and stabilized by a semiconductor saturable-absorber mirror with a
      single InGaAs quantum well. This system generates transform-limited 80-fs pulses
      near 1.3microm . An average power of 68 mW with fluctuation of much less than 1%
      is obtained with 3.8 W of absorbed pump power. The stability, efficiency,
      compactness, and potential for scaling to higher power of this system make it an
      attractive short-pulse source for applications.

PMID- 18084436
TI  - Holographic particle velocimeter using forward scattering with filtering.
AB  - We propose a new approach, forward-scattering holography with a filter, to
      holographic particle velocimetry for significant improvement in terms of
      increased effective aperture, modest laser power requirement, simple geometric
      setup, improved signal-to-noise ratio, and higher seeding density. We achieve
      this result by using a smooth (Guassian-like) high-pass filter during recording.

PMID- 18084437
TI  - Three-dimensional location of fluorescent inhomogeneities in turbid media by
      scanning heterodyne holography.
AB  - We describe and illustrate experimentally a method aimed at the three-dimensional
      (3-D) imaging of fluorescent inhomogeneities embedded in a turbid medium. The
      method utilizes incoherent scanning holography to capture 3-D information in a
      single two-dimensional scan and phase-sensitive heterodyne detection to reject
      multiply scattered light and to produce a single-sideband holographic record. The
      3-D imaging capability of the method is illustrated by an example.

PMID- 18084438
TI  - Broadband square-pulse operation of a passively mode-locked fiber laser for fiber
      Bragg grating interrogation.
AB  - A long-cavity, passively mode-locked erbium fiber laser operated in the square
      pulse regime is demonstrated as a useful light source for interrogating fiber
      Bragg grating arrays. Output pulses with 4-W peak-power, 10-ns pulse widths, and
      bandwidths greater than 60nm were used successfully to interrogate 2% fiber Bragg
      gratings.

PMID- 18084439
TI  - Laser-fabricated glass microlens arrays.
AB  - We report the fabrication of large, laser-formed refractive microlens arrays on
      doped borosilicate glass. Tuning the laser heat-source properties was found to
      give precise control over the melt process and the resulting lenslet geometries.
      Measurements of focal length, index, and surface shapes show excellent uniformity
      across these arrays.

PMID- 18084440
TI  - Cavity-mode selection in spontaneous emission from oriented molecules in a
      microparticle: errata.

PMID- 18084441
TI  - En-face coherence imaging using galvanometer scanner modulation.
AB  - We introduce a novel optical path-modulation technique for a low-coherence
      interferometric imaging system based on transverse scanning of the target with a
      galvanometric scanning-mirror pair. The path modulation arises when the beam that
      is incident upon one of the scanning mirrors does not fall on its axis of
      rotation. The method is demonstrated by the production of en-face low-coherence
      images of different objects such as a fiber-optic tip and a human retina invivo .

PMID- 18084442
TI  - Measuring wind speeds and turbulence with a wave-front sensor.
AB  - We analyze wave-front sensor (WFS) measurements taken with the 1.5-m telescope at
      the Starfire Optical Range in Albuquerque, N.M., of wind speeds in the turbulent
      atmospheric layers that cause seeing. The frozen-flow hypothesis suggests that
      atmospheric turbulence is located in thin horizontal layers and that turbulent
      features do not change over short time scales but are drawn along by the
      prevailing wind. Exploiting autocorrelation properties of the WFS data that
      result from these characteristics of atmospheric turbulence, we are able to
      measure the movements of individual layers. We also test the validity of the
      frozen-flow hypothesis.

PMID- 18084443
TI  - Transillumination imaging through scattering media by use of photorefractive
      polymers.
AB  - We demonstrate the use of a near-infrared-sensitive photorefractive polymer with
      high efficiency for imaging through scattering media, using an all-optical
      holographic time gate. Imaging through nine scattering mean free paths is
      performed at 800nm with a mode-locked continuous-wave Ti:sapphire laser.

PMID- 18084444
TI  - Scattering and spiraling of solitons in a bulk quadratic medium.
AB  - We analyze the interactions of (2+1) -dimensional parametric solitons and
      demonstrate nonplanar beam switching in a bulk X((2)) medium, which includes
      controllable soliton repulsion, spiraling, and fusion. An analytical model
      predicting the results of the soliton scattering is derived and verified by
      direct numerics.

PMID- 18084445
TI  - Continuous tuning of a continuous-wave periodically poled lithium niobate optical
      parametric oscillator by use of a fan-out grating design.
AB  - We report on a new periodically poled lithium niobate grating design with a
      continuous grating-period change (fan-out). We observed 350cm(-1) (80 nm at
      1.5microm) of complete spectral coverage at a constant temperature in a cw
      optical parametric oscillator. Complete spectral coverage is demonstrated by
      measurement of an absorption band of CO(2) .

PMID- 18084446
TI  - Highly efficient second-harmonic and sum-frequency generation of nanosecond
      pulses in a cascaded erbium-doped fiber:periodically poled lithium niobate
      source.
AB  - By combining erbium-doped fiber sources based on a large mode-area design and
      periodically poled lithium niobate, we have obtained single-pass conversion
      efficiencies of as much as 83% (energy efficiency) for second-harmonic generation
      into the near IR (768 nm) and of 34% for sum-frequency generation into the green
      (512 nm) for nanosecond pulses, using first-order quasi-phase matching. Pulse
      energies in excess of 80microJ of second harmonic have been obtained from systems
      pumped by a single laser diode.

PMID- 18084447
TI  - Phase correction in double-pass quasi-phase-matched second-harmonic generation
      with a wedged crystal.
AB  - Compensation for dispersive elements is necessary for efficient multiple-pass and
      intracavity nonlinear frequency-conversion devices. We describe the use of a
      wedged quasi-phase-matched crystal to compensate for the phase shifts introduced
      by mirrors in such devices, taking advantage of the periodic variation in the
      relative phases of the interacting waves in a quasi-phase-matching grating. A
      representative double-pass second-harmonic generation experiment with a 5-cm 
      long periodically poled lithium niobate crystal showed the expected conversion
      efficiency enhancement.

PMID- 18084448
TI  - Continuous-wave 532-nm-pumped singly resonant optical parametric oscillator based
      on periodically poled lithium niobate.
AB  - We report a continuous-wave (cw) 532-nm-pumped singly resonant optical parametric
      oscillator (SRO) based on periodically poled lithium niobate. The pump source is
      a commercial 5-W cw diode-pumped, multilongitudinal-mode, intracavity-doubled
      Nd:YVO(4) laser. Using a four-mirror ring SRO cavity and single-pass pumping, we
      achieved subwatt internal oscillation threshold, 56% quantum efficiency, and
      output tuning from 917 to 1266 nm.

PMID- 18084449
TI  - Generation of high-power blue light in periodically poled LiNbO(3).
AB  - We report the generation of 450-mW average blue (473-nm) power by frequency
      doubling of a diode-pumped 946-nm Nd:YAG laser. We achieved pulsed operation at a
      high repetition rate (~160kHz) by driving the relaxation oscillations of the
      laser. A 40% conversion efficiency to the second harmonic was obtained in a
      single-pass, extracavity, first-order, quasi-phase-matched process in which
      periodically poled lithium niobate (period 4.5microm , thickness 0.5mm , and
      length 15mm) at 140 degrees C was used. The resulting high-power blue beam was
      circular in profile and nearly diffraction limited, indicating that
      photorefractive effects do not appear to limit device performance.

PMID- 18084450
TI  - Grating-based transmission bandpass filters using dispersion-matched mode
      conversion.
AB  - A narrow-bandpass filter with a 15-dB signal-to-noise level is demonstrated using
      Bragg-grating assisted mode conversion within a tapered waveguide. The potential
      effects of such filters in wavelength-division multiplexing systems are
      discussed.

PMID- 18084451
TI  - Asynchronous phase-modulated optical fiber-ring buffer.
AB  - We investigate the dynamics of a 5-Gbit/s packet of ones and zeros loaded into a
      0.5-kbit, phase-modulated optical fiber-ring buffer. A new mode of operation is
      explored in which the cavity length of the buffer is slightly detuned from the
      frequency driving the phase modulator. We examine the conditions for successful
      packet loading and the packet storage behavior. In addition, relaxation
      oscillations, which affected the storage time of previous high-speed optical ring
      buffers, are nearly eliminated with a cw holding beam, and significantly enhanced
      storage times are obtained.

PMID- 18084452
TI  - Incompatibility of polarization-division multiplexing with wavelength-division
      multiplexing in soliton-transmission systems.
AB  - In a recent experiment it was demonstrated that polarization-division
      multiplexing was incompatible with wavelength-division multiplexing. We discuss a
      theoretical model that explains this result.

PMID- 18084453
TI  - All-optical switching and pulse routing in a distributed-feedback waveguide
      device.
AB  - Results of all-optical switching and pulse-routing experiments with a distributed
      feedback multiple-quantum-well (MQW) nonlinear waveguide, operating at 1.55microm
      , are reported. The MQW material has been engineered, through the controlled
      introduction of defects, to lower the carrier lifetime from 2.5 ns to 280 ps. The
      energy required for switching is of the order of 1 pJ or less, the switching time
      is ~600 ps , and the on-off contrast exceeds 17 dB.

PMID- 18084454
TI  - Increasing the free spectral range of silica waveguide rings for filter
      applications.
AB  - Ring resonators are promising building blocks for developing compact optical
      filters with arbitrary functions; however, a major challenge for planar waveguide
      filter implementations is to overcome the limited free spectral range (FSR) for a
      given core-to-cladding refractive-index difference (D) while maintaining low loss
      and a large range of coupling ratios. The loss and coupling of rings operating in
      the whispering-gallery-mode regime were investigated by use of Ge-doped silica
      waveguides with a low refractive-index difference (D=0.75%) . A FSR of 12 GHz
      with a loss of 0.36 dB/cm was demonstrated with coupling ratios of 30% (41%
      optimum).

PMID- 18084455
TI  - 4.7-W, 255-nm source based on second-harmonic generation of a copper-vapor laser
      in cesium lithium borate.
AB  - We have generated 4.7 W of UV (255-nm) radiation with wall plug efficiency of
      0.12% by frequency doubling the green (511-nm) output of a kinetically enhanced
      medium-scale copper-vapor laser (CVL) in cesium lithium borate (CLBO). Frequency
      doubling in beta -barium borate produced 3.9 W of UV radiation with wall plug
      efficiency of 0.1%. We found that conversion was better with CLBO because of the
      reduced constraints on CVL beam quality, less UV absorption, and smaller UV walk
      off.

PMID- 18084456
TI  - Tunable visible solid-state lasers based on second-harmonic generation of
      LiF:F(2) in potassium titanyl phosphate.
AB  - A new broadly tunable visible solid-state laser is reported. Wavelengths between
      550 and 610 nm are generated by intracavity frequency doubling of tuned and free
      running room-temperature pulsed LiF:F(2)(-) lasers in potassium titanyl
      phosphate. Second-harmonic energy of 1.3 mJ has been achieved, corresponding to a
      fundamental-to-second-harmonic conversion efficiency of 20%. Operation is
      optimized with respect to LiF:F(2)(-) laser parameters.

PMID- 18084457
TI  - Demonstration of long-term reliability of a 266-nm, continuous-wave, frequency
      quadrupled solid-state laser using beta-BaB(2)O(4).
AB  - We report what we believe to be the first operation of more than 1000 h of a 266
      nm (cw) frequency-quadrupled solid-state laser with a 100-mW output. We used beta
      BaB(2)O(4)(BBO) crystal grown by the Czochralski method to double the green-light
      (532-nm) wavelength, using an external resonant cavity. The green light was
      generated with an intracavity frequency-doubled Nd:YVO(4)laser pumped by a 4-W
      laser diode. When the incident 532-nm power on the external resonant doubler was
      500 mW, we generated 100 mW of cw 266-nm radiation with the BBO crystal. The
      degradation rate seems to be proportional to the strength of the UV optical
      electric field. We also obtained a relative intensity noise of -130dB/Hz at
      frequencies of 2 to 10 MHz for 266-nm laser light.

PMID- 18084458
TI  - Application of optimization algorithms to the design of diffractive optical
      elements for custom laser resonators.
AB  - We report what we believe to be the first applications of numerical optimization
      algorithms to the design of diffractive elements that customize the fundamental
      mode profile of a laser system. Standard design techniques treat these elements
      as specific phase-conjugation devices, which leads to performance loss when they
      are quantized to permit fabrication. Numerical optimization can account for
      quantization of the element to increase the effective performance. Also, it is
      shown that allowing a slight increase in the intrinsic loss of the cavity can
      substantially increase the fidelity of the fundamental mode of the customized
      cavity. The good discrimination qualities of the mode-selection elements are
      shown to be unaffected by this process.

PMID- 18084459
TI  - Simultaneous single-frequency oscillations on different transitions in a laser
      diode-pumped LiNdP(4)O(12) laser.
AB  - Simultaneous single-mode oscillations on different transitions were observed in a
      laser-diode-pumped microchip LiNdP(4)O(12) laser. The unusual modal-output
      characteristics of the laser were reproduced by multitransition-oscillation laser
      model equations that include cross saturation of population inversions with a
      strong spatial exponential decay and transition-dependent resonant reabsorption
      loss.

PMID- 18084460
TI  - High-power Lyman-alpha source generated with an ArF excimer laser.
AB  - We report high-power vacuum-ultraviolet (vuv) generation at the Lyman- alpha
      wavelength of 121.6nm , using a simple experimental system. vuv radiation is
      produced through two-photon-resonant difference-frequency mixing with a tunable
      ArF excimer laser and a Nd:YAG-pumped dye laser. Using phase-matched mixtures of
      Kr and Ar at a total pressure of 650 mbar, we produced 7-microJ energies at Lyman
      alpha in approximately 5ns (1.3kW) , as measured directly with a pyroelectric
      energy probe. Measurements indicate that higher powers are possible with system
      optimization. A tuning range of 0.1nm was achieved for a fixed gas mole fraction
      at a total pressure of 650 mbar. Qualitative agreement is found between measured
      tuning profiles and theoretical predictions.

PMID- 18084461
TI  - 2.5-W, continuous-wave, 629-nm solid-state laser source.
AB  - We report an efficient, high-power, cw, 629-nm laser source based on a diode
      pumped Nd:YAG laser and a periodically poled lithium niobate (PPLN) frequency
      converter. This device integrates two separate frequency-conversion steps in a
      single crystal, taking advantage of the ability to fabricate PPLN with nearly
      arbitrary grating periods and phase-matching temperatures. This device uses a
      single PPLN crystal that has two grating regions in series. The first region
      quasi-phase matches a standard optical parametric oscillator process
      (1064nm?1540nm +3450nm), and the second region quasi-phase matches a sum
      frequency process whereby the pump and the signal light make red light
      (1064nm+1540nm ?629nm). Using a four-mirror ring cavity, we were able to convert
      21% of the 1064-nm pump to 629-nm output, yielding 2.5W of red output with 11.8W
      of input.

PMID- 18084462
TI  - High-energy femtosecond pulse amlification in a quasi-phase-matched parametric
      amplifier.
AB  - A new type of solid-state femtosecond amplifier is demonstrated that is based on
      quasi-phase-matched parametric amplification. Such gain media are different from
      conventional solid-state amplifiers in that their amplification bandwidths and
      pump and signal wavelengths can be engineered. Furthermore, high gain is
      characteristic of parametric amplification, permitting extraction of high
      energies without the need to resort to multiple-pass configurations. We report a
      parametric chirped pulse amplification system in which femtosecond pulses from a
      mode-locked Er-doped fiber laser system are amplified to 1-mJ energies in a
      single pass by use of a 5-mm-long periodically poled LiNbO(3) (PPLN) crystal.
      This amplifier is pumped by 5-mJ and 0.5-ns pulses at 786 nm, demonstrating that
      limitations associated with a low optical-damage threshold for long pump pulses
      can be overcome because of the high nonlinearity of PPLN and that relatively
      simple Q -switched lasers can be used with such parametric amplifiers.

PMID- 18084463
TI  - Near-field propagation of terahertz pulses from a large-aperture antenna.
AB  - The near-field propagation behavior of terahertz (THz) pulses generated by a
      planar large-aperture photoconducting THz transmitter has been characterized. A
      simulation model based on Huygens-Fresnel diffraction theory has been developed
      that permits accurate prediction of the spatiotemporal profiles of the THz beam
      everywhere and gives excellent agreement with experimental measurements. Two key
      conclusions emerge from this research, namely, the realization that for practical
      laboratory setups one is always working in the near-field regime and that the
      proper temporal shape of the THz field at the antenna is one that rises rapidly
      but decays slowly.

PMID- 18084464
TI  - Optical trapping of metallic particles by a fixed Gaussian beam.
AB  - We demonstrate optical trapping of gold particles by use of single-beam gradient
      force. It is found that the radiation force exerted upon a gold particle can
      point toward the focus of the incident beam in two dimensions. Computations of
      the radiation force exerted upon a gold particle are also carried out to examine
      this phenomenon.

PMID- 18084465
TI  - Sensitive absorption spectroscopy with a room-temperature distributed-feedback
      quantum-cascade laser.
AB  - We report what we believe are the first spectroscopic measurements to be made
      with a room-temperature quantum-cascade distributed-feedback laser. Using
      wavelength modulation spectroscopy, we detected N(2)O and CH(4) in the chemical
      fingerprint wavelength range near 8microm . The noise equivalent absorbance for
      our measurement was 5 parts in 10(5), limited by excess amplitude modulation on
      the laser output, which corresponds to a 1-Hz bandwidth detection limit of 250
      parts N(2)O in 10(9) parts N(2) in a 1-m path length.

PMID- 18084466
TI  - Ultrahigh-sensitivity fiber-optic strain and temperature sensor.
AB  - We report ultrahigh-sensitivity static strain sensing (noise equivalent strain
      </=1.5n rms) by two fiber etalon cavities made from silica and fluoride fibers.
      The anomalous thermo-optic coefficient of fluoride glass fibers allows for
      determination of thermal and laser drift. This sensor is also capable of
      simultaneous strain and temperature measurement, with errors in strain and
      temperature of 6.4% and 0.68%, respectively.

PMID- 18084467
TI  - Bidimensional planar micro-optics for optochemical absorbance sensing.
AB  - A new approach for developing optochemical absorbance sensors is presented. The
      method is based on a planar micro-optic circuit in which an optochemically active
      membrane that responds to selective compounds is deposited in the device,
      yielding a part of the guiding planar structure. In this way the optical field is
      confined in the direction transverse to the substrate and controlled in the
      lateral direction by means of planar micro-optics components. High sensitivity of
      the device can be easily obtained because of the relatively long light paths
      through the membrane, and the response time is low because the analyte has to
      diffuse through a several-micrometer-thin membrane. Experimental results of
      measurements of the concentration of potassium are also presented to verify the
      possibilities of these devices as specific absorbance sensors.

PMID- 18084468
TI  - Birefringence characterization of biological tissue by use of optical coherence
      tomography.
AB  - An improved polarization-sensitive optical coherence tomography (OCT) system is
      developed and used to measure birefringence in porcine myocardium tissue and
      produce two-dimensional birefringence mapping of the tissue. Signal-to-noise
      issues that cause systematic measurement errors are analyzed to determine the
      regime in which such measurements are accurate. The advantage of polarization
      sensitive OCT systems over standard OCT systems in avoiding image artifacts
      caused by birefringence is also demonstrated.

PMID- 18084469
TI  - Reflection hologram for reconstructing deep images: errata.
AB  - On p. 1725 of Ref. 1, in the 20th line in the righthand column, the printed
      phrase "two-step time diffraction" should read as "two-step diffraction."

PMID- 18084470
TI  - Gram-Charlier matched filter for Shack-Hartmann sensing at low light levels.
AB  - A study has been made of a Gram-Charlier matched filter for Shack-Hartmann
      sensing of wave-front slopes. The method is based on modeling the point-spread
      function by an expansion in terms of Gauss-Hermite polynomials. We present
      results for several subapertureycoherence area sizes both with and without CCD
      read noise. A more accurate estimation of the local slopes can be achieved at low
      light levels in this way than with the standard first-moment estimator.

PMID- 18084471
TI  - Adaptive quadrature filters for multiple phase-stepping images.
AB  - We present a new technique for the recovery of local phase from multiple phase
      stepping fringe images that uses adaptive quadrature filters constructed by use
      of Bayesian estimation theory and complex-valued Markov random fields as prior
      models. It is shown that with this technique it is possible to perform accurate
      phase reconstructions even for extremely noisy fringe images and that the
      performance of this technique is nearly independent of the particular noise
      model, as long as the noise spectrum is wideband.

PMID- 18084472
TI  - Matrix treatment for partially polarized, partially coherent beams.
AB  - A matrix method is outlined for dealing with quasi-monochromatic, partially
      polarized light when spatial coherence is not necessarily complete and
      propagation occurs along beams. Both spatial coherence and polarization
      properties are described by a single 2x2 matrix whose elements have the structure
      of mutual intensity functions. Through a simple example it is shown that this
      matrix can account for differences that would not be revealed by a scalar
      treatment or by a locally defined polarization matrix.

PMID- 18084473
TI  - Full-field optical coherence microscopy.
AB  - We present a new microscopy system for imaging in turbid media that is based on
      the spatial coherence gate principle and generates in parallel a complete two
      dimensional head-on image without scanning. This system has been implemented in a
      commercial microscope and preserves the lateral resolution of the optics used.
      With a spatially incoherent source, speckle-free images with diffraction-limited
      resolution are recorded at successive depths with shot-noise-limited detection.
      The setup comprises a photoelastic modulator for path difference modulation and a
      two-dimensional CCD array and uses a multiplexed lock-in detection scheme.

PMID- 18084474
TI  - High-Q measurements of fused-silica microspheres in the near infrared.
AB  - Measurements of the quality factor Q approximately 8x10(9) are reported for the
      whispering-gallery modes (WGM's) of quartz microspheres for the wavelengths 670,
      780, and 850 nm; these results correspond to finesse f approximately 2.2x10(6) .
      The observed independence of Q from wavelength indicates that losses for the
      WGM's are dominated by a mechanism other than bulk absorption in fused silica in
      the near infrared. Data obtained by atomic force microscopy combined with a
      simple model for surface scattering suggest that Q can be limited by residual
      surface inhomogeneities. Absorption by absorbed water can also explain why the
      material limit is not reached at longer wavelengths in the near infrared.

PMID- 18084475
TI  - Cascaded phase shift and intensity modulation in aperiodic quasi-phase-matched
      gratings.
AB  - I propose a method for enhancing the cascaded phase shift of the fundamental wave
      associated with second-harmonic generation in aperiodic quasi-phase matched (QPM)
      gratings. The position and length of one of the domains were varied to maximize
      the cascaded phase shift. A maximum enhancement of 84% in the cascaded phase
      shift relative to a perfectly periodic QPM grating was obtained at a moderate
      fundamental input intensity without initial seeding of the second-harmonic wave.
      All-optical intensity modulation is also proposed with another optimized
      aperiodic QPM grating.

PMID- 18084476
TI  - Optically induced space-charge fields, dc voltage, and extraordinarily large
      nonlinearity in dye-doped nematic liquid crystals.
AB  - We have observed extraordinarily large optical nonlinearity in Methyl Red-doped
      nematic liquid-crystal film. Grating diffraction can be generated with an optical
      intensity as low as 40 microW/cm(2) , and a refractive-index change coefficient
      of more than 6 cm(2)/ W is obtained. The effect is attributed to formation of an
      optically induced dc space-charge field and to the resulting reorientation of the
      highly birefringent nematic director axis.

PMID- 18084477
TI  - Stability of a diode laser with phase-conjugate feedback.
AB  - An exact analysis is presented of the steady-state stability of a semiconductor
      laser subjected to feedback from a phase-conjugate mirror. Reduced stability
      occurs at low feedback whenever the effective external delay time is an integer
      multiple of the relaxation oscillation period. The role of a finite response time
      of the mirror is to enhance drastically the steady-state stability.

PMID- 18084478
TI  - All-optical AND gate based on coupled gap-soliton formation in a fiber Bragg
      grating.
AB  - We experimentally demonstrate an all-optical AND gate based on coupled gap
      soliton formation in an apodized fiber Bragg grating. A switching contrast of
      better than 17 dB is obtained with an incident pulse peak power of 2.5 kW.

PMID- 18084479
TI  - Oscillatory light loss within the cladding of a straight optical fiber:
      comparison with whispering-gallery modes.
AB  - Light propagating within the cladding of a straight optical fiber exhibits
      wavelength-dependent oscillatory loss that resembles the whispering-gallery modes
      of a bent fiber. This novel observation can be explained by interference of light
      only within the cladding and the buffer without any influence of the fiber core.
      The technique promises applications similar to those that are due to whispering
      gallery modes but without the additional requirement of having a bent fiber.

PMID- 18084480
TI  - Stable coupled conjugate solitary waves in optical fibers.
AB  - Four-wave mixing of an intense continuous-wave pump beam with an ultrashort
      soliton signal in an optical fiber is theoretically analyzed. A novel class of
      stable two-color coupled solitary waves is found. These vector parametric
      solitons represent the optimal frequency conversion of an ultrashort pulse.

PMID- 18084481
TI  - Self-similar evolution of self-written waveguides.
AB  - Numerical simulations show that channel waveguides can be self-written in
      photosensitive materials. As the waveguide evolves, its shape remains
      approximately constant, even though its depth and width change. We find an exact
      solution that describes this evolution, which we show to be self-similar. A wide
      variety of single-peaked beams form waveguides that converge to this solution.

PMID- 18084482
TI  - Femtosecond diode-pumped Nd:glass laser with more than 1 W of average output
      power.
AB  - We have demonstrated 175-fs pulses with 1 W and 300-fs pulses with 1.2 W of
      average output power at a pulse repetition rate of 117 MHz from a Nd:phosphate
      (Schott LG 760) glass laser pumped by a 1-cm-wide, 20-W diode laser bar. Stable
      soliton mode locking was achieved by use of an intracavity semiconductor
      saturable absorber mirror. We obtained more than 2 W of average power without
      mode locking. Using cylindrical cavity mirrors, we adapted the laser mode inside
      the Nd:glass to the highly elliptical pump beam in both dimensions (tangential
      and sagittal axes) while maintaining a nearly ideal circular TEM(00) output beam
      with M(2) approximately 1.2 . Overpumping the laser mode in the tangential plane
      and efficient unidirectional heat removal in the sagittal plane using a 0.8-mm
      thin Nd:glass also contributed to the good output-beam quality.

PMID- 18084483
TI  - Gain characteristics of tellurite-based erbium-doped fiber amplifiers for 1.5
      microm broadband amplification.
AB  - The signal-gain characteristics of tellurite-based erbium-doped fiber amplifiers
      are clarified based on spectroscopic properties and signal-gain measurements. The
      potential of tellurite-based erbium-doped fiber for use as a broadband light
      source is also described.

PMID- 18084484
TI  - Femtosecond high-sensitivity, chirp-free transient absorption spectroscopy using
      kilohertz lasers.
AB  - A simple method is demonstrated for high-sensitivity, chirp-free measurements of
      femtosecond (fs) transient absorption over the entire bandwidth of a white-light
      continuum probe. This technique uses phase-sensitive detection, with spectral
      scanning and simultaneous adjustment of the time delay between pump and probe
      pulses; it permits a direct measurement of spectra undistorted by chirp at all
      time scales, limited only by the resolution of the fs source. The method is
      applied to study the ultrafast relaxation dynamics of pi-conjugated oligomers and
      semiconductor nanocrystals.

PMID- 18084485
TI  - Ultrashort pulses generated by mode-locked lasers with either a slow or a fast
      saturable-absorber response.
AB  - We present a new exact solution for ultrashort pulses generated by passively mode
      locked lasers, taking into account the slow and the fast parts of the
      semiconductor saturable-absorber response in the nonsaturated limit.

PMID- 18084486
TI  - Dispersion-free fiber transmission for femtosecond pulses by use of a dispersion
      compensating fiber and a programmable pulse shaper.
AB  - We demonstrate nearly distortionless 2.5-km fiber transmission of sub-500-fs
      pulses, using a combination of standard single-mode fiber, dispersion
      compensating fiber, and a programmable pulse shaper for simultaneous quadratic
      and cubic dispersion compensation. The dispersion-compensating fiber corrects the
      bulk of the quadratic and the cubic phases for the single-mode fiber, and the
      fiber-pigtailed programmable pulse shaper exactly compensates the residual
      dispersion terms. Together these elements permit complete recompression of
      pulses, which first broaden by ~400 times in the single-mode fiber.

PMID- 18084487
TI  - Wideband phase-noise measurement of mode-locked laser pulses by a demodulation
      technique.
AB  - A new method is proposed and demonstrated for measuring the phase noise (pulse
      timing fluctuations) of mode-locked lasers. The instantaneous phases of the pulse
      intensity are extracted in a time domain, and the phase-noise power spectral
      density is calculated from the demodulated signals. Compared with the
      conventional method based on the single-sideband phase-noise measurement, the
      proposed method has a larger dynamic range and a wider frequency span. The phase
      noise of a mode-locked Cr:LiSAF laser is measured for 50-mHz-1-MHz Fourier
      frequencies.

PMID- 18084488
TI  - Noise reduction of page-oriented data storage by inverse filtering during
      recording.
AB  - Two novel techniques for eliminating deterministic noise from a page-oriented
      memory are presented. The first technique equalizes the output response of ON
      pixels by adjustment of the exposure of each pixel during the recording of each
      data page. A test image transmitted through the system measures the spatial
      nonuniformities, and the appropriate inverse filter is imposed upon the data page
      and recorded in the storage material. On readout, the output signal values are
      then spatially uniform, perturbed only by random noise sources. Experimental
      results of using this predistortion technique in a pixel-matched holographic
      storage system are shown. Under conditions of high volumetric density, raw bit
      error-rate (BER) improvements of 6-8 orders of magnitude are obtained (from 10(
      4) to <10(-10)). The second technique uses a phase shift during holographic
      storage to subtract from bright OFF pixels. Under conditions of low spatial light
      modulator contrast, BER improvements of 6 orders of magnitude (from 10(-2) to 10(
      8)) are demonstrated.

PMID- 18084489
TI  - Optical fuzzy systems based on efficient implementation of a fuzzy associative
      memory.
AB  - We propose efficient implementation of a fuzzy associative memory system based on
      a fuzzy-sets decomposition technique. The technique involves decomposing the
      input fuzzy sets of a fuzzy associative memory into orthogonal subsets so
      multiple fuzzy rules can be superimposed without loss of information. This
      technique can significantly reduce the optical hardware and computation needs of
      fuzzy associative memory systems.

PMID- 18084490
TI  - Intracavity electromagnetically induced transparency.
AB  - The effect of intracavity electromagnetically induced transparency (EIT) on the
      properties of optical resonators and active laser devices is discussed
      theoretically. Pronounced frequency pulling and cavity-linewidth narrowing are
      predicted. The EIT effect can be used to reduce classical and quantum-phase noise
      of the beat note of an optical oscillator substantially. Fundamental limits of
      this stabilization mechanism as well as its potential application to high
      resolution spectroscopy are discussed.

PMID- 18084491
TI  - Combined optical-infrared single-ion frequency standard.
AB  - A combined infrared-optical frequency-standard scheme has been demonstrated with
      a single ion of ytterbium. The optical (2)S(1/2)-(2)D(5/2) reference transition
      at 411 nm and the infrared (2)F(7/2)-(2)D(5/2) 3.43-microm transition were driven
      sequentially. The structure of the infrared (2)F(7/2)-(2)D(5/2) reference
      transition at 3.43 microm has also been studied. Infrared transition linewidths
      of 300 kHz were observed. The output of a Nd:YAG laser and an extended-cavity
      diode laser were difference-frequency mixed in a crystal of AgGaS(2) to produce
      narrow-linewidth light at 3.43 microm . Both lasers were frequency stabilized to
      high-finesse reference cavities.

PMID- 18084492
TI  - Optical data storage in microfibers.
AB  - Tests of optical data storage in arrays of microfibers confirm its applicability
      and potential for higher storage densities than those achievable with
      conventional holographic data storage. Arrays of single-mode microfibers, spaced
      0.78 microm apart and 60 microm long, were generated in a photopolymer film with
      four laser beams and simultaneously inscribed with Lippmann-Bragg fringes by use
      of a counterpropagating beam. Following the curing steps, spectra of white light
      retroreflected from a single fiber exhibit the reconstructed spectral lines of
      the multiwavelength laser used in the recording step; 10(11) bits/cm(2), or
      10(13) bits on a compact disk, appear to be recordable.

PMID- 18084493
TI  - Narrow-band resonance-ionization and fluorescence imaging in a mercury-vapor
      cell.
AB  - Characteristics of a novel type of ultranarrow-band image detector have been
      experimentally studied. The principle of this new imaging approach is to detect a
      resonance-ionization and (or) fluorescence-imaging signal formed on a thin planar
      cell filled with atomic vapor. A planar vapor cell with a thickness of 1.6 mm was
      used for imaging 253.7-nm radiation by Hg atoms. One- and two-dimensional images
      were produced and detected with ionization and fluorescence-signal acquisition.
      The feasibility of atomic-vapor image detectors with a spectral resolution of
      several megahertz is discussed.

PMID- 18084494
TI  - Optical measurement of the viscoelastic and biochemical responses of living cells
      to mechanical perturbation.
AB  - We have developed an optical method for real-time monitoring of cellular motion
      in a natural environment with nanometer resolution. From the motion driven by
      small optical forces, we measured dynamic viscoelastic responses of living cells
      in the linear reversible region. Cytoplasmic gel-to-sol transition that was due
      to the disruption of the actin-filament framework was detected, and a linear
      release of Ca(2+) from intracellular storage that was related to submicrometer
      cell deformation was observed. The method was shown to be a powerful tool for
      studying the natural response of cells to mechanical perturbation.

PMID- 18084495
TI  - Generation of tunable 187.9-196-nm radiation in beta-BaB(2)O(4): errata.
AB  - In Ref. 1, the first full sentence in the right-hand column of p. 1608 should
      read as: 'Although BBO is phase matchable down to 187 nm and shorter in this
      configuration without a very large (2-4 degrees ) change in theta (and hence in
      d(eff)), and B2 is also suitable to accommodate the phase matching, tunability
      below 187.9 nm becomes limited by the exponential increase in crystal
      absorption.'

PMID- 18084496
TI  - Modal decomposition of partially coherent flat-topped beams produced by multimode
      lasers.
AB  - We present a simple mathematical model giving a possible description of a
      partially coherent light beam exhibiting a flat-topped transverse intensity
      profile. Such a model allows us to deduce the modal distribution inside a
      multimode stable optical cavity, assuming that the modes are of the Hermite-Gauss
      type. The analytical expression used to represent flat-topped profiles is of the
      flattened Gaussian type and leads to an exact, closed-form expression for the
      M(2) factor of the output beam. An analogous procedure could be used to treat the
      general problem of deducing the modal distribution inside a laser cavity starting
      from intensity measurements of the output beam.

PMID- 18084497
TI  - Interference in light scattering from slightly rough dielectric layers.
AB  - The scattering of light from a slightly rough surface overlying a reflecting
      surface is investigated. It is shown that the long-scale component of the
      roughness spectrum plays a critical role in the scattering patterns obtained. The
      scattered interference patterns are critically dependent on small variation of
      the rms height of the long-scale component of the roughness. Conventional
      perturbation theory is found to be invalid in cases in which interference
      phenomena in the scattering are of importance. A model is proposed that
      quantitatively describes the measured angular intensity distributions.

PMID- 18084498
TI  - Using dynamic low-coherence interferometry to image Brownian motion within highly
      scattering media.
AB  - Dynamic low-coherence interferometry was used to measure Brownian motion of
      submicrometer particles within highly scattering media. Strong rejection of
      multiply scattered light was obtained by combination of a coherence gate with a
      confocal microscope, thus allowing particle characterization methods generally
      reserved for optically dilute materials to be applied to optically concentrated
      suspensions. The Brownian diffusion coefficient of highly scattering media was
      determined with an accuracy better than 5%. Furthermore, we show that spatial
      variations in the Brownian diffusion coefficient can be imaged with an axial
      resolution determined by the coherence length of the light source (~30 mum) . The
      experiments also show broadening of the power spectrum as a function of depth
      into the sample, most likely as a result of detecting multiply scattered light.

PMID- 18084499
TI  - Plasma waveguide formation in predissociated clustering gases.
AB  - We report on the use of a novel technique to create a plasma waveguide suitable
      for guiding high-intensity laser pulses in underdense plasmas. A narrow channel
      of a clustering gas is dissociated with a low-intensity prepulse. This prepulse
      is followed by a high-intensity, focused laser pulse. The high absorption of the
      clusters surrounding the dissociated atomic channel causes the remaining annulus
      of clusters to become highly ionized, leaving low-density plasma in the center.
      We have interferometrically probed the formation of this channel with picosecond
      laser pulses.

PMID- 18084500
TI  - Heating by absorption in the focus of an objective lens.
AB  - We derive an integral solution for the local heating of a linearly absorbing,
      uniform medium exposed to strongly focused light. Numerical results for local
      heating under typical multiphoton microscopy and optical trapping conditions are
      presented for various aperture angles. In contrast with common Gaussian beam
      approximations, our model employs the focal-intensity distribution as described
      by the point spread function of the lens. In this way, the model also accounts
      for axial heat transportation, which results in a lower prediction for the
      temperature increase. For an aperture of 1.2 (water immersion), irradiation with
      100 mW of 850-nm light for 1 s increases the local temperature of water by 0.2 K.
      Heating of water by linear absorption can be ruled out as a limiting factor in
      standard multiphoton-excitation microscopy.

PMID- 18084501
TI  - Nonlinear self-switching and multiple gap-soliton formation in a fiber Bragg
      grating.
AB  - We report, for the first time to our knowledge, the experimental observation of
      quasi-cw nonlinear switching and multiple gap-soliton formation within the
      bandgap of a fiber Bragg grating. As many as five gap solitons with 100-500-ps
      durations were generated from a 2-ns pulse at a launched peak intensity of
      approximately 27 GW/cm(2). A corresponding increase in the grating transmission
      from 3% to 40% of the incident pulse energy was observed.

PMID- 18084502
TI  - 5.2-5.6-microm source tunable by frequency conversion in a GaAs-based waveguide.
AB  - A tunable mid-IR source obtained by difference-frequency generation is
      demonstrated in a selectively oxidized GaAsAlAs multilayer waveguide. We designed
      the waveguide to present the required form birefringence for phase matching of
      the nonlinear interaction. We took special care to lower losses for the mid-IR
      radiation. IR tunability from 5.2 to 5.6 mum was achieved by variation of the
      waveguide temperature and one pump wavelength. IR output power as great as 0.12
      muW was obtained with the product of two pump powers of 7 mW(2). Losses of ~50
      cm(-1) were measured for the mid-IR radiation. These losses are attributed to
      surface scattering.

PMID- 18084503
TI  - Trapping of slowly moving or stationary two-color gap solitons.
AB  - We address the important problem of excitation of gap solitons of a parametric
      nature, which are sustained in periodically corrugated frequency-doubling media
      near Bragg resonance with both the fundamental frequency and its second harmonic.
      We demonstrate that a zero-velocity soliton can be trapped in a finite Bragg
      structure by the quiescence of two counterpropagating moving solitons, which in
      turn might be formed by injection of appropriate light pulses at a single carrier
      frequency.

PMID- 18084504
TI  - Incoherent switching between multistable cavity solitons in a semiconductor
      optical resonator.
AB  - We demonstrate numerically a two-dimensional threefold storage scheme based on
      different types of solitary waves in the transmitted field of a semiconductor
      planar resonator. Switching between among different solitary waves can be
      achieved by use of a weak incoherent switching beam.

PMID- 18084505
TI  - Threshold couplings of phase-conjugate mirrors with two interaction regions.
AB  - Using the grating-action method, we determine the threshold coupling strengths of
      three generic examples of phase-conjugate mirrors with two interaction regions:
      the cat conjugator, the mutually incoherent beam coupler, and the interconnected
      ring mirror.

PMID- 18084506
TI  - Thermally induced self-focusing and optical beam interactions in planar strontium
      barium niobate waveguides.
AB  - We present an experimental study of thermally induced self-focusing effects and
      interactions of incoherent light beams in strontium barium niobate waveguides.
      Depending on the input power, a single parallel beam is strongly focused inside
      the sample up to diameters of several micrometers. For higher input power we
      observe the splitting of the beam in a sequence of several spots. We demonstrate
      that these thermally induced refractive-index patterns can be used to focus and
      deflect an incoherent guided probe beam in the waveguide with time constants
      below 1 ms.

PMID- 18084507
TI  - Spatial solitary waves and patterns in type II second-harmonic generation.
AB  - The existence of Turing patterns and of spatial solitary waves that arise from a
      polarization instability of the fundamental field is predicted in type II second
      harmonic generation in a quadratically nonlinear optical cavity. The analogy
      between these dissipative structures and those studied in absorptive optical
      bistability is pointed out.

PMID- 18084508
TI  - Extended-range optical time domain-reflectometry system at 1.65 microm based on
      delayed Raman amplification.
AB  - We describe both theoretical and experimental results obtained in an
      investigation of a new technique for increasing the dynamic range of 1.65-microm
      optical time domain-reflectometry (OTDR) systems. The technique utilizes delayed
      Raman amplification of a 1.65-microm signal pulse by a 1.53-microm pump pulse.
      Amplification occurs when the two pulses overlap, and this position is determined
      by the initial delay between the pulses and the fiber dispersion. An increase in
      dynamic range of 17.5 dB has been observed, and the OTDR backscattered Rayleigh
      signal was detected up to 100 km. No significant noise penalty is introduced as a
      result of the directionality of the Raman gain.

PMID- 18084509
TI  - Experimental demonstration of a Raman effectbased optical transistor.
AB  - We demonstrate optical pulse switching and amplification based on simultaneous
      Raman and Kerr effects in a fiber-loop mirror. Stimulated Raman scattering is
      shown to play a dominant role in the transfer function of the loop with highly
      germania-doped fibers, in agreement with theoretical predictions. Optical
      switching of a 100-ps signal pulse with an amplification factor of 10 was
      demonstrated in a 20-mol.% GeO(2)-doped fiber.

PMID- 18084510
TI  - Ring-doped cladding-pumped single-mode three-level fiber laser.
AB  - We propose and theoretically analyze three-level cladding-pumped fiber lasers in
      which the laser-active dopant is placed in a ring around a single-mode core. A
      ring-doped laser can work efficiently at wavelengths with strong small-signal
      absorption. This is otherwise difficult in a cladding-pumped fiber. Moreover,
      ring doping makes the laser less sensitive to quenching of the laser-active
      dopant and to excited-state absorption of the lasing field. In simulations of a
      Yb(3+) -doped fiber laser, ring doping increased the slope efficiency to 62%, up
      from 13% for a conventional core-doped fiber.

PMID- 18084511
TI  - Single-longitudinal-mode fiber laser with a passive multiple-ring cavity and its
      application for video transmission.
AB  - A single-longitudinal-mode erbium-doped fiber laser with a passive multiple-ring
      cavity (MRC) is proposed for the first time to the authors' knowledge. The laser
      is fundamentally structured by insertion of three different short ring cavities,
      which serve as mode filters, into the main cavity. When it is combined with a
      mode-restricting intracavity fiber Bragg grating, the MRC resonator ensures
      single-longitundinal-mode laser oscillation. The laser can successfully suppress
      side-mode frequencies of as much as 1 GHz and provide an output power of 23 mW
      with a side-mode suppression ratio of 51 dB at 1533 nm. The short-term linewidth
      of the laser output measured is ~2 kHz . The ability of this fiber laser to act
      as an AM transmitter source is also demonstrated.

PMID- 18084512
TI  - Determination of the optimum absorption coefficient in Cr(4+):forsterite lasers
      under thermal loading.
AB  - We present the results of a novel experimental and numerical investigation aimed
      at minimizing thermal loading effects in room-temperature Cr(4+): forsterite
      lasers. In the model we numerically calculated the incident pump power required
      for oscillation threshold to be attained by taking into account pump absorption
      saturation, pump-induced thermal gradients inside the crystal, and the
      temperature dependence of the upper-state fluorescence lifetime. Excellent
      agreement was obtained between model predictions and experimental threshold data.
      We then used the model to calculate the optimum absorption coefficient that
      minimizes the incident threshold pump power. At a crystal boundary temperature of
      15 degrees C the optimum value of the absorption coefficient was numerically
      determined to be 0.64 cm(-1) . Such optimization studies, which are readily
      applicable to other laser systems, should make a significant contribution to the
      improvement of the power performance of Cr(4+): forsterite lasers at room
      temperature.

PMID- 18084513
TI  - Coupling of concentric semiconductor microring lasers.
AB  - Coupling between whispering-gallery modes of concentric microcavity lasers was
      analyzed, and a closed-form three-dimensional vectorial solution for the coupled
      fields was obtained. Experiments performed with concentric gain-guided vertical
      cavity ring lasers resulted in regimes of resonant coupling in good agreement
      with the theory.

PMID- 18084514
TI  - Continuous-wave Raman laser in H(2).
AB  - Recent developments in high-finesse cavities now make broadly tunable, continuous
      wave Raman lasers possible. The design and preliminary characterization of what
      is to the authors' knowledge the first continuous-wave Raman laser in H(2) are
      presented. The threshold is currently at 2 mW of pump, making diode laser pumping
      possible. The maximum photon conversion efficiency observed was 35% at 7.6 mW of
      pump power.

PMID- 18084516
TI  - Analysis of the effect of numerical aperture on Pr:ZBLAN upconversion fiber
      lasers.
AB  - Theoretical analyses show that the use of high-numerical-aperture (NA) fibers can
      significantly increase the conversion efficiency of a blue Pr(3+) -doped fluoride
      fiber upconversion laser and reduce the pump-power threshold. A record high
      efficiency of ~14% and a low 1017-nm threshold of ~30 mW were achieved
      experimentally with a fiber with a NA of ~0.39.

PMID- 18084515
TI  - Partially end-pumped Nd:YAG slab laser with a hybrid resonator.
AB  - A Nd:YAG slab is partially end pumped by a diode laser stack with three diode
      laser bars. The pumped volume has a rectangular cross section. A hybrid
      resonator, which is stable in the plane of small dimension and is off-axis
      unstable in the plane of large dimension of the gain cross section, was used to
      yield highly efficient laser operation at diffraction-limited beam quality. The
      laser design and experimental results are reported.

PMID- 18084517
TI  - Intraband carrier kinetics and picosecond pulse shaping in field-enhanced bulk
      semiconductor absorbers.
AB  - Picosecond pulse propagation through a field-enhanced waveguide bulk
      semiconductor saturable absorber is studied numerically. Fast switching from
      unsaturated absorption to delayed strong saturation and gain, as well as the
      predicted dependence of saturation energy on electric field, is based on
      intraband carrier kinetics and electric-field dynamics in the absorber and can
      lead to improved, controllable pulse shaping.

PMID- 18084518
TI  - Amplitude and phase measurements of femtosecond pulse splitting in nonlinear
      dispersive media.
AB  - Frequency-resolved optical gating is used to characterize the propagation of
      intense femtosecond pulses in a nonlinear, dispersive medium. The combined
      effects of diffraction, normal dispersion, and cubic nonlinearity lead to pulse
      splitting. The role of the phase of the input pulse is studied. The results are
      compared with the predictions of a three-dimensional nonlinear Schrodinger
      equation.

PMID- 18084519
TI  - Dynamic spatial replenishment of femtosecond pulses propagating in air.
AB  - We present numerical simulations of nonlinear pulse propagation in air whereby an
      initial pulse is formed, absorbed by plasma generation, and subsequently
      replenished by power from the trailing edge of the pulse. This process can occur
      more than once for high-power input pulses and produce the illusion of long
      distance propagation of one self-guided pulse.

PMID- 18084520
TI  - Gouy shift and temporal reshaping of focused single-cycle electromagnetic pulses.
AB  - We discuss exact solutions of Maxwell's equations that describe the evolution of
      single-cycle electromagnetic pulses. The solutions are applied to recent
      observations of the diffraction transformation of terahertz pulses. In
      particular, we elucidate the role of the Gouy shift in the temporal reshaping and
      polarity reversals of single-cycle terahertz pulses.

PMID- 18084521
TI  - Origin of third-order optical nonlinearity in Au:SiO(2) composite films on
      femtosecond and picosecond time scales.
AB  - Three sorts of probe laser, which have pulse durations of 200 fs, 35 ps, and 70
      ps, were employed in the measurement of the third-order nonlinear optical
      susceptibility x((3)) in Au:SiO(2) composite films in a degenerate four-wave
      mixing scheme. We found that the composite films at their absorption peak (~550
      nm) had a maximum x((3)) , which depends strongly on the pulse width of the probe
      laser. The value of x((3)) measured with a 70-ps laser was ~30 times larger than
      that measured with a 200-fs laser. The time-resolved measurements revealed that
      the optical nonlinearity on the femtosecond time scale is attributable mainly to
      contributions from the interband electric-dipole transition (especially at low
      concentrations) and partly to those from hot electrons rather than being
      dominated by hot-electron excitation in the picosecond regime.

PMID- 18084522
TI  - Spontaneous-emission spectrum of the nonlasing supermodes in semiconductor laser
      arrays.
AB  - It is shown that the interference between amplified spontaneous emission into the
      nonlasing supermode and the laser field of a semiconductor laser array causes
      spatial hole burning, which couples the dynamics of the amplified spontaneous
      emission with the laser field. In particular, phase locking between the amplified
      spontaneous emission and the lasing mode leads to the formation of a spectral
      triplet composed of in-phase relaxation oscillation sidebands and an out-of-phase
      line at the lasing frequency.

PMID- 18084523
TI  - Particle sizing in concentrated suspensions by use of steady-state, continuous
      wave photon-migration techniques.
AB  - We demonstrate a new approach for determining particle-size distribution in
      concentrated suspensions from spectral measurement of isotropic scattering
      coefficients by use of steady-state, continuous-wave photon-migration techniques.
      Successful recovery of particle-size distribution for TiO(2) suspensions in the
      form of log-normal functions is achieved through a regularized inverse algorithm,
      into which a synthesized scheme of Marquardt and Tikhonov regularizations has
      been incorporated. Our results for dense TiO(2) suspensions with three different
      particle concentrations are in excellent agreement with the size distribution as
      measured with x-ray sedimentation.

PMID- 18084524
TI  - Fabrication of high-mechanical-resistance Bragg gratings in single-mode optical
      fibers with continuous-wave ultraviolet laser side exposure.
AB  - The mechanical resistance of single-mode fibers containing fiber Bragg gratings
      inscribed with cw UV laser irradiation is almost identical to that of pristine
      fiber. The median breaking strength of the gratings' Weibull distribution is more
      than 5 GPa, and the m value is of the order of 70. Based on a dynamic fatigue
      model, a Bragg grating lifetime of 50 years with a failure probability of 0.001
      is predicted, assuming a constant applied stress of 0.96 GPa.

PMID- 18084525
TI  - Unfolding of an unstable singularity point into a ring.
AB  - It is well known that phase singularities, in general lines in space, are
      topologically stable features of a wave field. An exception is a pointlike
      singularity, which is unstable and deforms into a ring or disappears when a small
      perturbation is applied. Recently, Nye showed how such an event can be understood
      as an unfolding of a higher-order dislocation [J. Opt. Soc. Am. A (to be
      published)]. We present an optical implementation of this model and show
      experimentally that the focal region of a lens contains points of zero intensity
      on the optical axis that deform into rings when a small amount of spherical
      aberration is applied to the system.

PMID- 18084526
TI  - Convergent, recursive phase reconstruction from noisy, modulated intensity
      patterns by use of synthetic interferograms.
AB  - We present a novel method of rapidly convergent phase reconstruction from noisy
      and high-fringe-density intensity patterns without a priori information. We
      define an error function that incorporates the measured intensity data to ensure
      the convergence. The error function is the absolute value of the cosine of the
      difference of the reconstructed phase and the unknown phase, i.e., a calculated
      or a synthetic interferogram.

PMID- 18084527
TI  - Quasi-discrete Hankel transform.
AB  - A quasi-discrete Hankel transform (QDHT) is presented as a new and efficient
      framework for numerical evaluation of the zero-order Hankel transform. A discrete
      form of Parseval's theorem is obtained for the first time to the authors'
      knowledge, and the transform matrix is discussed. It is shown that the S factor,
      defined as the products of a truncated radius, is critical to building the QDHT.

PMID- 18084528
TI  - Unified statistically independent region processor for deterministic and
      fluctuating targets in nonoverlapping background.
AB  - Recently, new approaches for location of a target in nonoverlapping noise, which
      are optimal in the maximum-likelihood sense, have been proposed. In particular,
      different methods for deterministic or fluctuating targets have been developed.
      We propose a unified and optimal processor for a target with either known or
      unknown gray levels. We demonstrate the efficiency and robustness of this method
      in comparison with previously developed processors.

PMID- 18084529
TI  - Focusing through an interface: scanning and localizing the intensity.
AB  - Focusing light through an interface leads to an aberrated intensity distribution
      that is highly extended with a relatively low peak intensity. We present a
      method, using a well-chosen annular aperture, that can greatly improve the
      localization of the intensity about a prescribed point on the axis. Also, the
      intensity at that point can be increased significantly. By continuously varying
      the annulus radii, we can scan the intensity peak through the second medium. This
      localization and scanning method has possible applications in three-dimensional
      imaging and lithography.

PMID- 18084530
TI  - Dynamics of incoherent bright and dark self-trapped beams and their coherence
      properties in photorefractive crystals.
AB  - Using the coherent density approach, we study the propagation dynamics of
      incoherent bright and dark beams in biased photorefractive crystals. We show
      that, under appropriate initial conditions, bright as well as darklike incoherent
      quasi-solitons can be established in this material system. Our numerical
      simulations demonstrate that the coherence properties of these beams can be
      significantly affected by the self-trapping process.

PMID- 18084531
TI  - One-dimensional steady-state photorefractive spatial solitons in centrosymmetric
      paraelectric potassium lithium tantalate niobate.
AB  - We report the first observation of spatial one-dimensional photorefractive
      screening solitons in centrosymmetric media and compare the experimental results
      with recent theoretical predictions. We find good qualitative agreement with
      theory.

PMID- 18084532
TI  - Collisions between type II two-dimensional quadratic solitons.
AB  - We report experimental and numerical results that describe collisions between two
      dimensional type II quadratic solitons excited in a KTP crystal by fundamental
      waves of orthogonal polarization. Our results provide experimental evidence of
      the possibility of both inelastic collision (when two quadratic solitons merge at
      input into a single soliton at output) and quasi-elastic collision.

PMID- 18084533
TI  - Biexcitonic fingerprint in the nondegenerate four-wave-mixing signal of weakly
      confined cadmium sulfur quantum dots.
AB  - Nondegenerate four-wave mixing is analyzed with respect to biexcitonic
      contributions in the third-order nonlinear susceptibility x((3)) . The presence
      of biexcitons causes a distinct asymmetry in the frequency dependence of self
      diffraction. By measurement of the dependence of the intensity of the self
      diffracted signal on detuning between the two incident laser beams, the biexciton
      binding energy is determined to be E(XX)=7.8 meV for cadmium sulfur quantum dots
      of R=7.5 nm embedded in glass. Thus, even for weakly confined II-VI quantum dots
      with R~2.7a(B) , a confinement-induced enhancement of E(XX) was found.

PMID- 18084534
TI  - Four-photon absorption in the single-crystal polymer bis(paratoluene) sulfonate.
AB  - Strong four-photon absorption corresponding to Im[x((7)) (-?; ?, -?, ?, -?, ?, 
      ?, ?)] has been measured for the first time to the authors' knowledge with 100-fs
      pulses at 1600 nm in the single-crystal polymer poly[bis (p-toluene sulfonate)]
      of 2, 4-hexadiyne-1, 6-diol. The transition involved is from the even-symmetry
      ground state into the vibronic subband of the dominant, even-symmetry, excited
      two-photon state at an energy of 2.7 eV.

PMID- 18084535
TI  - Bistable nonspecular reflection at a nonlinear-linear local interface.
AB  - Nonspecular reflection at a nonlinear-linear dielectric interface with local Kerr
      nonlinearity is analyzed. The Fresnel reflectivity and the variational solution
      are explicitly given in a closed form. Bistable switching of the interface is
      demonstrated by numerical simulations based on the monotonic iteration procedure.

PMID- 18084536
TI  - Bichromatic frequency conversion in potassium niobate.
AB  - Two frequency components of an IR laser beam near 980 nm are simultaneously
      coupled into two adjacent longitudinal modes of a passive ring resonator. A
      potassium niobate crystal inside the resonator converts the circulating IR light
      into coherent blue radiation. The total conversion efficiency is enhanced by a
      factor of 1.4 compared with that of conventional single-mode intracavity second
      harmonic generation with the same circulating total power, and we obtain a total
      output power of 560 mW from 780-mW IR light incident upon the cavity. The spectra
      of the generated blue radiation and the circulating IR light contain a number of
      equidistant frequency components that are due to consecutive sum- and difference
      frequency mixing.

PMID- 18084537
TI  - Frequency shifting through cascaded second-order processes in a N-(4-nitrophenyl)
      L-prolinol crystal.
AB  - We exploit the high second-order susceptibility of the organic crystal N-(4
      nitrophenyl)-L-prolinol to accomplish, through a cascaded second-order process,
      wavelength conversion of a signal pulse (from 1.16 to 1.14 microm) under the
      action of a pump pulse (at 1.15 microm). In a 2.8-mm-thick crystal, wavelength
      conversion with unit gain was obtained with a pump peak intensity as low as 9
      MW/cm(2) . At low intensities, in the limit of negligible conversion where the
      cascading effect can be described through an effective third-order
      susceptibility, we derive |(x)((3))(eff) | approximately 2.4 x 10(-17) m(2)/V(2),
      which is ~10(2) larger than the nonresonant (x)((3)) of conjugated polymers or
      semiconductors.

PMID- 18084538
TI  - Amplification of photon echo signals by use of a fiber amplifier.
AB  - The efficiency of photon-echo processes typically lies in the 0.1-1% range. For
      many photon-echo-based applications suggested in optical storage and all-optical
      communication the photon-echo output pulses would need to be used as input data
      to a new photon-echo process. In such cases amplification of the photon-echo
      output signals would be necessary for an acceptable signal-to-noise ratio to be
      obtained. We show that a Pr-doped ZBLAN fiber is able to produce significant
      amplification of photon-echo signals generated in Pr-doped Y(2)SiO(5) at 606 nm.

PMID- 18084539
TI  - Efficient broadband intracore grating LP(01)-LP(02) mode converters for chromatic
      dispersion compensation.
AB  - LP(01)-LP(02) mode converters based on UV-written intracore gratings have been
      fabricated for chromatic-dispersion compensation. The mode converters operate in
      transmission at wavelengths near 150 nm with spectral bandwidths of 14-25 nm and
      coupling efficiencies of as much as 90%. A large negative dispersion of -335
      ps/(nm km) is obtained for a compensator consisting of the mode converter and a
      1490-m-long few-mode fiber. The compensator shows negative dispersion over a
      wavelength region of 5 nm. Its figure of merit is estimated to be 370 ps/(nm dB).

PMID- 18084540
TI  - Nondegenerate four-wave-mixing measurements of a resonantly induced refractive
      index grating in a Nd:YAG amplifier.
AB  - Two optical waves (at 1064 nm) were used to resonantly induce a population
      grating in a flash-lamp-pumped Nd:YAG rod, and a nonresonant wave (at 1054 or 694
      nm) was used to read (with a diffraction efficiency of as much as 1% or 0.3%,
      respectively) the refractive-index grating caused by the difference in the
      polarizability of the excited and the unexcited Nd ions. Comparisons of
      experimental results and numerical calculations gave the dependence of the ratio
      of the real and the imaginary parts of the resonant susceptibility of Nd:YAG at
      1064 nm on the pump power.

PMID- 18084541
TI  - High-power monolithic unstable-resonator solid-state laser.
AB  - We report the operation of a diode-pumped monolithic Q-switched unstable
      resonator solid-state laser that generates 2.15-mJ, 2-ns pulses in a single
      transverse mode and a single longitudinal mode. We show that the unstable
      resonator is effective in suppressing the spatial and the temporal instability of
      the laser beam in a disk-shaped laser whose transverse dimension is comparable
      with or larger than its longitudinal dimension.

PMID- 18084542
TI  - Enhanced Q switching in double-clad fiber lasers.
AB  - A novel cladding pumped Nd(3+) fiber laser operating in an enhanced Q-switched
      regime with a stable repetition rate is described. By exploiting fiber
      nonlinearities in the laser cavity, we demonstrated a peak power of 3.7 kW
      enhanced by an order of magnitude greater than that of conventional Q-switched
      fiber devices. Pulse durations as short as 2 ns have been achieved.

PMID- 18084543
TI  - Self-Q-switched Nd:YVO4 microchip lasers.
AB  - We have observed giant pulses from cw pumped, monolithic Nd:YVO(4) microchip
      lasers, several hundred times the cw level, with pulse lengths less than 2 ns,
      which cannot be accounted for by conventional gain switching. These pulses occur
      as the second longitudinal mode starts to oscillate and can be described by the
      inclusion of gain-related effects in the formation of a stable cavity.

PMID- 18084544
TI  - Suppression of chaotic oscillations in a microchip laser by injection of a new
      orbit into the chaotic attractor.
AB  - Suppression of chaotic instability arising in a Nd:YVO(4) microchip laser subject
      to frequency-shifted optical feedback is accomplished by injection of one of the
      periodic orbits into the bifurcation region of another chaotic system driven by
      pump modulation. Various periodic patterns, which do not exist in the original
      chaotic attractor, can be extracted from the chaotic oscillation by use of this
      nonfeedback chaos-control technique.

PMID- 18084545
TI  - Dual-wavelength emission from optically cascaded intersubband transitions.
AB  - Dual-wavelength intersubband emission at 8 and 10 microm is reported in a three
      level quantum-well system in which one electronic state is at the same time the
      lower level of the first optical transition and the upper level of the second.
      Results are presented for two different AlInAs/GaInAs quantum cascade structures
      featuring single-well active regions with two vertical transitions or double-well
      active regions with one diagonal and one vertical transition. Laser action has
      been achieved between the excited states of the single-well device and on the
      diagonal transition of the double-well structure. In the latter case the
      wavelength can be electric-field tuned by means of the Stark effect also above
      threshold.

PMID- 18084546
TI  - Far-infrared second-harmonic generation and pulse characterization with the
      organic salt DAST.
AB  - We generated the second harmonics of pulses in the far-infrared region (30-55
      microm), using the organic salt dimethylamino-4-N-methylstilbazolium tosylate
      (DAST). We demonstrate that DAST can be used to characterize ultrashort pulses in
      a spectral region where no other materials are available. To illustrate the need
      for such characterizations, we show the effects of propagation through air on the
      shape of ultrashort far-infrared pulses.

PMID- 18084547
TI  - Ultrafast pulsed mode effects on the performance of grating-assisted output
      couplers of finite extent.
AB  - The performance of grating-assisted output couplers of finite extent excited by
      finite ultrafast pulsed modes is characterized numerically by the finite
      difference time-domain method. The results for pulsed excitations with extremely
      long pulse envelopes are compared with those that contain only a few optical
      cycles for gratings that are both long and short compared with the equivalent
      pulse length. We demonstrate that the shortest length of either the grating or
      the pulse dictates the far-field performance of the grating-assisted output
      couplers.

PMID- 18084548
TI  - Frequency-stable and ultranarrow-linewidth semiconductor laser locked directly to
      an atomic-cesium transition.
AB  - We describe a new method for semiconductor laser FM noise reduction. A Doppler
      free Faraday resonance in Cs vapor provided optical feedback, and FM sideband
      saturation spectroscopy in a second Cs cell provided electronic feedback. The
      combined optical and electronic feedback allowed us to reduce the low-frequency
      FM noise power by more than 6 orders of magnitude, which resulted in a sub-100-Hz
      linewidth semiconductor laser locked directly to an atomic transition frequency.

PMID- 18084549
TI  - Nearly diffraction-limited laser focal spot obtained by use of an optically
      addressed light valve in an adaptive-optics loop.
AB  - We demonstrate correction of laser wave-front distortions by use of an adaptive
      optical technique based on a light valve. The setup consists of an achromatic and
      adjustable-sensitivity wave-front sensor and a wave-front corrector relying on an
      optically addressed liquid-crystal spatial light modulator. Experimental results
      with strongly aberrated beams focused close to the diffraction limit are
      presented for the cw regime. Additional experiments with pulses and measurement
      of damage thresholds show that this approach is relevant for spatial phase
      correction of ultraintense laser pulses.

PMID- 18084550
TI  - Low-V(pi) electro-optic modulator with a high-microbeta chromophore and a
      constant-bias field.
AB  - A low half-wave voltage V(pi) of 1.57 V was obtained with a 2-cm-long
      birefringent polymer waveguide modulator at a wavelength of 1.3 microm by use of
      a modulator design with a constant-bias electric field and a high-microbeta
      chromophore. The design allows the maximum achievable electro-optic coefficient
      of the material to be utilized. This electro-optic coefficient can be more than
      twice as high as the residue value that is used by conventional modulator
      designs, after fast partial relaxation following poling.

PMID- 18084551
TI  - Measurement and calculation of the two-dimensional backscattering Mueller matrix
      of a turbid medium.
AB  - We present both experimental and Monte Carlo-based simulation results for the
      diffusely backscattered intensity patterns that arise from illumination of a
      turbid medium with a polarized laser beam. A numerical method that allows the
      calculation of all 16 elements of the two-dimensional Muller matrix is used;
      moreover, it is shown that only seven matrix elements are independent. To
      validate our method, we compared our simulations with experimental measurements,
      using a turbid medium consisting of 2.02-microm -diameter polystyrene spheres
      suspended in deionized water. By varying the incident polarization and the
      analyzer optics for the experimental measurements, we obtained the diffuse
      backscattering Mueller matrix elements. The experimental and the numerical
      results are in good agreement.

PMID- 18084552
TI  - Improvement in robustness of the statistically independent region snake-based
      segmentation method of target-shape tracking.
AB  - We propose a technique to increase the robustness of a snake-based segmentation
      method originally introduced to track the shape of a target with random white
      Gaussian intensity upon a random white Gaussian background. Because these
      statistical conditions are not always fulfilled with optronic images, we describe
      two improvements that increase the field of application of this approach. We
      first show that regularized whitening preprocessing allows one to apply the
      original method successfully for a target with a correlated texture upon a
      correlated background. We then introduce a simple multiscale approach that
      increases the robustness of the segmentation against the initialization of the
      snake (i.e., the initial shape used for the segmentation). These results provide
      a robust and practical method for determination of the reference image for
      correlation techniques.

PMID- 18084553
TI  - Light modulation from crossed phase gratings.
AB  - A new device, consisting of two phase gratings oriented with a small angle
      between their grating grooves, acts as a variable-profile diffraction grating
      that produces variations in the diffraction orders as the illumination region is
      moved across the device. Combinations of phase gratings that optimize the effect
      and act as passive light modulators are given. An experiment that demonstrates
      the principle is described.

PMID- 18084554
TI  - Detection of a small defect on a rough surface.
AB  - We report experimental results that show that the far-field correlation function
      is sensitive to a small local change in rough-surface geometry, where the speckle
      spatial correlation rather than the sample ensemble average is adopted. The
      angular cross-correlation function of the far-field speckles scattered by one
      dimensional random rough surfaces is measured when a polarized beam of light is
      incident upon the rough surface from vacuum, where one part of the surface used
      is a thin dielectric film deposited upon a glass substrate and the other part is
      identical to the first except for a localized defect. We envisage application of
      this sensitivity property to inspection of a sample with a defect by means of
      speckle mapping.

PMID- 18084555
TI  - Efficient broadband second-harmonic generation by dispersive achromatic nonlinear
      conversion using only prisms.
AB  - Using a lossless dispersive apparatus consisting of six prisms, optimized to
      match a second-harmonic crystal phase-matching angle versus wavelength to second
      order, we efficiently doubled tunable fundamental light near 660 nm over a range
      of 80 nm, using a 4-mm-long type I beta -barium borate crystal without tuning the
      crystal angle. Another set of six prisms after the crystal realigned the
      propagation directions of the various second-harmonic frequencies to be collinear
      to within 1/4 spot diameter in position and 200microrad in angle. The measured
      conversion efficiency of a 40-mJ, 5-ns fundamental pulse was 10%.

PMID- 18084556
TI  - Symmetry breaking and self-oscillations in intracavity vectorial second-harmonic
      generation.
AB  - We show that, in vectorial intracavity second-harmonic generation, symmetry
      breaking occurs if the input amplitude exceeds a critical value. The resulting
      asymmetric stationary solutions are characterized by a second harmonic that is
      independent of the input amplitude. The solutions can destabilize through Hopf
      bifurcations, leading to self-oscillations with pronounced antiphase dynamics. We
      demonstrate that symmetry breaking can be exploited for flip-flop operation.

PMID- 18084557
TI  - Near- to mid-infrared picosecond optical parametric oscillator based on
      periodically poled RbTiOAsO(4).
AB  - We describe a Ti:sapphire-pumped picosecond optical parametric oscillator based
      on periodically poled RbTiOAsO(4) that is broadly tunable in the near to mid
      infrared. A 4.5-mm single-grating crystal at room temperature in combination with
      pump wavelength tuning provided access to a continuous-tuning range from 3.35 to
      5microm , and a pump power threshold of 90 mW was measured. Average mid-infrared
      output powers in excess of 100 mW and total output powers of 400 mW in ~1-ps
      pulses were obtained at 33% extraction efficiency.

PMID- 18084558
TI  - Nonlinear phase shift and all-optical switching in quasi-phase-matched quadratic
      media.
AB  - Recently it was shown that in quasi-phase-matched quadratic media the average
      intensities are subject to an induced Kerr effect. We analytically study the
      influence of this induced cubic nonlinearity on the amplitude and phase
      modulation of the fundamental wave and predict efficient all-optical switching.

PMID- 18084559
TI  - Wavelength-division multiplexing isolation fiber filter and light source using
      cascaded long-period fiber gratings.
AB  - The author has successfully demonstrated a novel all-fiber wavelength-division
      multiplexing (WDM) isolation filter with more than 20 equally spaced loss peaks
      within a 60-nm band and a WDM light source with an output of 21 equally spaced
      wavelengths within 30% amplitude variation.

PMID- 18084560
TI  - Dark-soliton-like pulse-train generation from induced modulational polarization
      instability in a birefringent fiber.
AB  - Theory and experiments show that the nonlinear development of the modulational
      polarization instability of an intense light beam in a normally dispersive, low
      birefringence optical fiber leads to ultrashort dark-soliton-like trains with
      repetition rates in the terahertz range in the polarization orthogonal to the
      pump.

PMID- 18084561
TI  - Diode-pumped 250-W zigzag slab Nd:YAG oscillator amplifier system.
AB  - A laser-diode-pumped zigzag slab Nd:YAG master oscillator power amplifier (MOPA)
      system featuring high pulse energy and high average power was developed for
      pumping of an ultrashort-pulse laser system. The MOPA system consists of an
      oscillator, a preamplifier, two postamplifiers, and image-relay telescopes. The
      postamplifiers have an angle-multiplexed ring-type double-pass configuration. A
      pulse energy of 1.26 J and an average power of 251 W were obtained at a
      repetition rate of 200 Hz. The frequency-doubled power when a LiB(3)O(5) crystal
      was used was 105 W at a repetition rate of 170 Hz. The intensity profiles of the
      fundamental and the second harmonic are nearly top-hat shaped and are suitable
      for pumping.

PMID- 18084562
TI  - Microchip laser-pumped continuous-wave doubly resonant optical parametric
      oscillator.
AB  - We report what we believe to be the first use of a multilongitudinal-mode
      frequency-doubled microchip laser to pump a doubly resonant optical parametric
      oscillator (OPO). This compact OPO is based on potassium titanyl phosphate (KTP)
      and operates with a low pump power threshold of 35 mW. The OPO output consists of
      a single pair of signal and idler modes even though it is pumped with a
      multilongitudinal-mode pump laser. We achieved smooth tuning (1.7 GHz) of the
      output frequencies by temperature tuning of the pump laser.

PMID- 18084563
TI  - Intensity correlations in filtered phase-diffusing light.
AB  - Light undergoing phase diffusion displays a Lorentzian line shape: Here,
      electrical filtering techniques are used to examine the correlations among
      different spectral regions under this line shape. The experiment involves delayed
      self-heterodyne measurements of the output from a single-mode semiconductor
      laser. Two filters are tuned to isolate the signal contributions from opposite
      wings of the spectrum, and the transmitted intensities are shown to be strongly
      correlated in some regimes and strongly anticorrelated in others.

PMID- 18084564
TI  - Compact broadband 5-bit photonic true-time-delay module for phased-array
      antennas.
AB  - Photonic true-time-delay (TTD) lines offer many advantages over their electronic
      counterparts and are attracting more and more research effort. We demonstrate a
      device with 32 TTD lines (5-bit) based on substrate guided-wave propagation
      combined with slanted photopolymer volume phase gratings on a quartz substrate.
      System design, device fabrication, optimization of fan-out intensity uniformity,
      and device performance evaluation are addressed as well. The device has a
      measured bandwidth of up to 2.4 THz and a measured fan-out delay step of 50 ps.
      The fan-out beam intensity uniformity is within +/-10% . The packing density is
      2.5 delay lines/cm(2), which is to our knowledge the highest demonstrated thus
      far.

PMID- 18084565
TI  - Generation of 16-fs, 10-TW pulses at a 10-Hz repetition rate with efficient
      Ti:sapphire amplifiers.
AB  - We describe a two-stage Ti:sapphire amplifier laser system that is capable of
      producing 16-fs pulses of 10-TW peak power at a 10-Hz repetition rate. Thin solid
      etalons were used to control gain narrowing and gain saturation during
      amplification. A cylindrical mirror expander was used to permit compensation of
      the dispersion of the system. An efficiency greater than 90% of the theoretical
      maximum for conversion of 532-nm pump light to 790-nm radiation is demonstrated.

PMID- 18084566
TI  - Chirped-pulse programming of optical coherent transient true-time delays.
AB  - Programming an optical coherent transient true-time delay device with two
      frequency-chirped pulses provides a novel means of performing broadband (> >GHz)
      true-time delay with a wide dynamic range of delays with fine temporal
      resolution. We have demonstrated true-time delays exceeding 2micros with sub-100
      ps resolution. Chirped-pulse programming has the advantages over the previously
      proposed brief pulse programming [Opt. Lett. 21 1102 (1996)] of reduced
      instantaneous power requirements and the ability to control the true-time delay
      by frequency shifting the programming pulses.

PMID- 18084567
TI  - Observation of pure rotational absorption spectra in the nu2 band of hot H(2)O in
      flames.
AB  - We present measurements of absorption spectra of hot-water vapor generated in a
      propane-air flame in the far-infrared region of the spectrum from 0.1 to 3.5 THz
      (3.3 to 117cm(-1)). Transitions within the rotational manifold of both the ground
      and the nu(2)=1 vibrational levels were observed. The measurements are in good
      agreement with calculations of the predicted absorption spectra at 1300 K based
      on tabulated line intensities, whereas predicted theoretical line widths were
      found to be approximately one third too narrow.

PMID- 18084568
TI  - Breakdown of the slowly varying envelope approximation in the self-focusing of
      ultrashort pulses.
AB  - We show theoretically and experimentally that with ultrashort pulses much longer
      than a single optical cycle, the effects of self-steepening and space-time
      focusing are important for describing the nonlinear dynamics of self-focusing.
      Asymmetric temporal splitting of the pulse envelope is observed in which the
      relative magnitudes of the peaks are reversed as the input power is increased.

PMID- 18084569
TI  - One-dimensional logarithmic harmonic synthetic discriminant function filters for
      shift-, scale-, and projection-invariant pattern recognition.
AB  - We introduce a new approach for shift-, scale-, and projection-invariant pattern
      recognition that combines the harmonic expansion and the synthetic discriminant
      function approaches by use of a synthetic discriminant function filter with equal
      order one-dimensional logarithmic harmonic components. Because projection
      invariance in one direction is guaranteed by the harmonics, the required number
      of training images is much fewer than with classical synthetic discriminant
      function filters.

PMID- 18084570
TI  - Noiseless independent signal and power amplification.
AB  - We present a noiseless optical amplifier comprising a signal-amplifying feed
      forward loop and a power-amplifying injection-locked laser. We demonstrate that
      the signal amplifier can attain a signal-transfer coefficient limited solely by
      the quantum efficiency of our in-loop photodetector and that we can independently
      amplify the optical power while leaving the normalized intensity-noise spectral
      density of the input field unchanged.

PMID- 18084571
TI  - Room-temperature persistent spectral hole burning of Eu(3+) in sodium
      aluminosilicate glasses.
AB  - Persistent spectral hole burning has been observed at 77 K, 180 K, and room
      temperature for Eu(3+) in sodium aluminosilicate glass melted under a reducing
      atmosphere. In particular, room-temperature persistent spectral hole burning is
      reported for the first time to our knowledge in Eu(3+) -doped materials. The
      persistent hole is accompanied by no antiholes and lasts for 1 h at least. The
      thermal stability of the hole is greater than that of a persistent hole burned
      for Eu(3+) in sodium aluminosilicate glass melted in air.

PMID- 18084572
TI  - High-speed temporal characterization and visualization of spatial light
      modulators and flat-panel displays.
AB  - An apparatus that can characterize and visualize temporal dynamics of spatial
      light modulators (SLM's) and flat-panel displays is constructed and evaluated by
      use of a commercially available SLM. The apparatus is based on the stroboscopic
      video sampling method and has a temporal resolution of the order of microseconds,
      permitting measurement of a long event (>100ms) with a high signal-to-noise
      ratio. Experimental results demonstrate the visualization of the temporal image
      sequencing and addressing in an SLM.

PMID- 18084573
TI  - High-isolation polarization-independent optical quasi-circulator with a simple
      structure.
AB  - A high-isolation polarization-independent optical quasi-circulator with a simple
      structure is proposed. A Porro prism is employed in this kind of device for what
      is believed to be the first time. Because a Porro prism is used, light beams pass
      back and forth through the main elements in the device. Thus the number of
      elements used in the device is decreased, and the device structure is simplified.
      A four-port quasi-circulator with monomode fibers was assembled and tested at the
      1.55-microm wavelength. Its insertion loss, isolation, and return loss are ?1.63
      , ?60 , and ?55.6 dB , respectively.

PMID- 18084574
TI  - High-efficiency subwavelength diffractive element patterned in a high-refractive
      index material for 633 nm.
AB  - We propose the use of high-index materials for the fabrication of subwavelength
      diffractive components operating in the visible domain. This approach yields a
      reduction of fabrication constraints and an improvement of theoretical
      performance. A blazed grating with subwavelength binary features and with a
      period of 5.75 wavelengths is designed and fabricated in a TiO(2) layer coated
      upon a glass substrate. The first-order diffraction efficiency measured with a He
      Ne laser beam is 83%, which is slightly larger than that achieved theoretically
      by the best standard (continuous profile) blazed grating fabricated in glass with
      the same period.

PMID- 18084575
TI  - Separation of changes in light scattering and chromophore concentrations during
      cortical spreading depression in rats.
AB  - We used near-infrared spectroscopy to separate tissue scattering changes from
      changes in cerebral oxyhemoglobin and deoxyhemoglobin and the redox state of
      cytochrome- c -oxidase. A separate term of the transport scattering coefficient
      (micro(s)(?)) was included in a modified Lambert-Beer equation. It is shown by
      diffusion equation analysis that there is a simple relationship between the
      differential path-length factor (D(a)) and its scattering equivalent (D(s)) . The
      method was applied to cortical spreading depression (CSD) data recorded through
      the skulls of rats. Biphasic changes in micro(s)(?)of +/-0.1mm(-1)were observed
      during CSD's that spread with a velocity of ~5mm/min . The method proposed has
      the promise to permit monitoring of scattering changes noninvasively in humans
      during cortical activation or pathophysiological conditions.

PMID- 18084576
TI  - Analysis of forward scattering of diffuse photon-density waves in turbid media: a
      diffraction tomography approach to an analytic solution.
AB  - We present a model of the forward problem for diffuse photon-density waves in a
      turbid medium containing a spherical inhomogeneity, using diffraction tomographic
      (DT) methods. Recently, by use of DT methods, the forward problem was
      investigated [Opt. Express 1, 6 (1997); www.osa.org] assuming weak perturbations
      from the background medium but an arbitrary inhomogeneity structure. We apply DT
      concepts to a forward problem solution that permits strong perturbations but
      requires a spherical inhomogeneity. We show that this model is consistent with
      previous DT results and discuss the application of this new model.

PMID- 18084577
TI  - Sonoluminescent tomography of strongly scattering media.
AB  - A novel optical imaging technique called sonoluminescent tomography was developed
      for cross-sectional imaging of strongly scattering media noninvasively.
      Sonoluminescence, which was generated internally in the medium by cw ultrasound,
      was used to produce a two-dimensional image of an object embedded in a scattering
      medium by means of raster scanning the medium. The image had a high contrast and
      good spatial resolution. The spatial resolution was limited by the focal-spot
      size of the ultrasound, and one could improve the resolution by tightening the
      focus. This inexpensive imaging technique has potential applications in medicine
      and other fields related to scattering media.

PMID- 18084578
TI  - All-reflective Michelson, Sagnac, and Fabry-Perot interferometers based on
      grating beam splitters.
AB  - All-reflective Michelson, Sagnac, and Fabry-Perot interferometers based on
      grating beam splitters are experimentally demonstrated at a wavelength of 1064
      nm. A 1200-groove/mm grating diffracting 0 and -1 orders with an efficiency of
      48.2% for each order was used as a near-50/50 beam splitter. The all-reflective
      Sagnac and Michelson interferometers were formed by reintroducing both of the
      diffracted beams back to the grating. The Fabry-Perot interferometer was formed
      in a Littrow configuration by using a 1700-groove/mm grating with a blazing
      efficiency of 91% as a cavity coupler. These interferometers encompass all the
      fundamental configurations of all-reflective laser interferometric gravitational
      wave detectors, promising improved wave-front quality by avoiding volume thermal
      effects in transmissive optics under high-power laser illumination.

PMID- 18084579
TI  - Lyapunov stability criteria for zonal adaptive-optics systems.
AB  - Lyapunov stability criteria are derived for a first-order closed-loop adaptive
      optics servo system, resulting in a linear matrix equation that includes the
      system geometry, servo parameters, and wave-front reconstruction matrix. It is
      demonstrated that instability zones depend on the choice of matrix estimator and
      the servo-loop gain. Divergence of the error propagator gives results that are
      consistent with the Lyapunov equation. The significance of these results is
      discussed.

PMID- 18084580
TI  - Linear phase retrieval for wave-front sensing.
AB  - Phase retrieval from one or more intensity measurements is a potentially powerful
      and appealing technique for real-time adaptive-optics wave-front sensors. Under
      the assumption of small wave-front phase excursions, one is able to derive an
      exact solution to the inverse problem given three or more intensity measurements
      with known phase offsets. Applications include a high-order wave-front sensor to
      correct for residual aberrations in an adaptive-optics system in tandem with a
      low-resolution Hartmann-Shack wave-front sensor. The formula can also furnish
      mathematical insights into the full nonlinear phase-retrieval task.

PMID- 18084581
TI  - Beam displacement at diffractive structures under resonance conditions.
AB  - A beam of light incident upon a diffractive structure can under resonance
      conditions be subject to a rather large lateral displacement. The effect is
      demonstrated with a Gaussian profile beam and two geometries based on a waveguide
      grating and a single-mode waveguide.

PMID- 18084582
TI  - Extension of the generalized multipole technique to three-dimensional anisotropic
      scatterers.
AB  - New expansions are derived for the simulation of three-dimensional anisotropic
      scatterers with the generalized multipole technique (GMT). This extension of the
      GMT makes possible the investigation of subtle phenomena such as the interaction
      of light with realistic crystals or magneto-optic materials.

PMID- 18084583
TI  - Optical parametric oscillation in periodically poled lithium niobate driven by a
      diode-pumped Q-switched erbium fiber laser.
AB  - We describe what is to our knowledge the first nanosecond periodically poled
      lithium niobate (PPLN) optical parametric oscillator (OPO) driven by a fiber
      laser. The source was frequency doubled by a PPLN sample before pumping a second,
      20-mm-long, PPLN crystal. The OPO threshold was <10muJ, with pump depletions of
      as much as 45% and a tunable signal range of 945-1450 nm (1690-4450-nm idler
      range). We demonstrated 130-nm signal tuning by varying the pump wavelength and
      doubling crystal's temperature. Also, we achieved 15-nm tuning with all crystals
      at a constant temperature. The results demonstrate the potential of the fiber
      laser:PPLN combination for practical, versatile, and tunable sources.

PMID- 18084584
TI  - Image transmission through a thick dynamic distorter by the photorefractive
      fanning effect.
AB  - A new method of one-way image transmission through a thick dynamic distorter
      without the need for a reference beam or four-wave mixing is demonstrated. In
      this method there are only one object beam and one sampling beam. The response
      time of the photorefractive crystal must be much longer than the fluctuation
      period of the dynamic distorter. Thus the crystal responds only to the time
      averaged intensity pattern of a rapidly varying object beam. The images,
      reconstructed with high fidelity, are picked up through the photorefractive
      fanning effect.

PMID- 18084585
TI  - Absolute measurement of the second-order nonlinearity profile in poled silica.
AB  - Measurement of the thin nonlinearity profile of poled silica by the Maker fringe
      technique has been impossible because of total internal reflection (TIR) at the
      back surface of the sample. We demonstrate that this limitation can be removed by
      placing a prism against each face of the sample, thus avoiding TIR. This novel
      technique allows, for the first time to our knowledge, the nonlinearity profile
      of a thin film to be inferred by the Maker fringe technique. Applied to a silica
      sample thermally poled under standard conditions (275 degrees C and 5.3 kV for 30
      min), it suggests a Gaussian profile with a 1/e width of 8 mum and a maximum
      d(33) of 0.34 pm/V.

PMID- 18084587
TI  - Observation of mighty morphing spatial solitons.
AB  - The experimental observation of bright spatial solitons in the form of mighty
      morphing solitons is reported for the first time to the author's knowledge. These
      are Gaussian-like beams of elliptical cross section, which appear to change their
      shape constantly as they propagate. Saturation of the nonlinear medium is shown
      to progress logarithmically.

PMID- 18084586
TI  - Two-dimensional bright spatial solitons stable over limited intensities and ring
      formation in polydiacetylene para-toluene sulfonate.
AB  - Spatial soliton formation in the bulk single-crystal polydiacetylene para-toulene
      sulfonate has been studied experimentally. The unique nonlinearity of this
      material at 1600 nm leads to stable solitons below an intensity maximum, and for
      higher intensities the input beams form a ring and a soliton.

PMID- 18084588
TI  - Optimal dispersion maps for wavelength-division-multiplexed soliton transmission.
AB  - We propose an advantageous dispersion-management scheme for wavelength-division
      multiplexed soliton transmission in which optimal launch points are obtained
      whose locations are independent of the fibers' dispersion parameters. Inasmuch as
      using such optimal launch points minimizes dispersively shed radiation, it is
      possible to optimize the transmission simultaneously in several different
      channels. For the particular case of a two-step dispersion map we demonstrate
      that this result can be achieved by proper choice of the fiber lengths.

PMID- 18084589
TI  - Chirped solitons with strong confinement in transmission links with in-line fiber
      Bragg gratings.
AB  - We demonstrate that the use of fiber gratings to reverse periodically the pulse
      chirp in transmission links allows us to produce stable chirped optical solitons
      with fast-decaying tails. The interaction between neighboring pulses is reduced
      from that of the usual soliton system as a result of pulse chirping and strong
      confinement, making possible dense information packing. Such a pulse is an
      attractive candidate for use as an information carrier in optical transmission
      systems with ultralarge capacities of approximately 100 Gbits/s.

PMID- 18084590
TI  - Digital operation of an ytterbium-doped two-mode fiber interferometric optical
      intensity switch.
AB  - Digital operation of an all-optical intensity switch is demonstrated in a two
      mode interferometer constructed from ytterbium-doped fiber. We clamp the
      resonantly enhanced phase shift responsible for the switching by allowing the
      fiber to lase, resulting in a bistable, digital response. The degree of phase
      shift at the clamping point can be controlled by adjustment of the laser
      threshold, and for complete switching (phase shift of pi) the power length
      product PL(pi) was estimated to be 1.3 mW m . Isolation of 11 dB was observed,
      with switching speed limited by the relaxation time of ytterbium.

PMID- 18084591
TI  - Ultrafast intensity modulation by Raman gain for all-optical in-fiber processing.
AB  - We present experimental results on ultrafast intensity modulation using the Raman
      effect and demonstrate 10-Gbit/s selective pulse erasure. The technique is both
      broadband and polarization insensitive and has a potential speed in excess of 500
      Gbits/s. In addition to performing pulse erasure, this all-optical modulator can
      shape pulses as a precise, soft aperture scalpel and create short, dark pulses.

PMID- 18084592
TI  - Dispersion-managed solitons at normal average dispersion.
AB  - We find that in a dispersion-managed fiber, in which the strength of the
      dispersion management is above some threshold, solitons can exist with normal
      average dispersion. When the normal average dispersion is below some limiting
      value there exist two soliton solutions with the same pulse duration and
      different pulse energies. When the normal average dispersion is above this
      limiting value, no soliton exists. Both higher-energy and lower-energy solitons
      are dynamically stable in the parameter range that we considered.

PMID- 18084593
TI  - Guided-mode resonance Brewster filter.
AB  - A new type of optical filter is predicted theoretically and verified
      experimentally. The filter operates under guided-mode resonance conditions in a
      thin-film waveguide grating. A high-efficiency reflection filter response is
      produced at the Brewster angle at which TM reflection is classically prohibited.
      Low-reflectance sidebands are obtained that are adjacent to the resonance peak
      induced by the Brewster effect in the neighborhood of the resonance peak. A
      double-layer waveguide grating yields 94% experimental reflectance at the thin
      film Brewster angle for a Gaussian laser beam with TM polarization at the 1064-nm
      wavelength.

PMID- 18084594
TI  - Environmentally stable picosecond ytterbium fiber laser with a broad tuning
      range.
AB  - We demonstrate a widely tunable passively mode-locked fiber laser operating at a
      fundamental frequency of 80 MHz with an output power of 90 mW. The laser is
      capable of generating 5-ps pulses in the region 1010-1064 nm. A strong mode
      locking mechanism promoted by frequency-shifted feedback allows us to operate in
      simultaneous Q-switched and mode-locked regimes and to obtain peak power in
      excess of 1.2 kW.

PMID- 18084595
TI  - Short-pulse laser interferometric measurement of absolute gas densities from a
      cooled gas jet.
AB  - We report on the use of a novel technique to measure the gas density from a
      pulsed gas jet. Deuterium gas is fully ionized with an intense picosecond laser,
      and the resulting electron density is measured by interferometric probing with a
      second picosecond pulse. We have applied this technique to characterize a
      cryogenically cooled, high-density gas jet.

PMID- 18084596
TI  - Single-shot wave-front measurements of high-intensity ultrashort laser pulses
      with a three-wave interferometer.
AB  - A simple new three-wave interferometric technique is used to measure, for what is
      believed to be the first time, the wave front of femtosecond ultrahigh-peak-power
      pulses carrying a strong B integral (B = 5.26+/-0.15) in a single shot. Wave
      front distortions of a terawatt-class laser system are measured with good
      accuracy (lambda/50) and discussed. These distortions can significantly reduce
      the focused peak intensity, emphasizing the necessity of implementing adaptive
      optics in ultrahigh-intensity chirped-pulse amplification lasers.

PMID- 18084597
TI  - Ultrashort dephasing-time measurements in Nile Blue polymer films.
AB  - Optical dephasing measurements using degenerate four-wave mixing (DFWM) were
      performed on thin dye-polymer films at room temperature. Incoherent light
      centered at 575 nm was used as a source for ultrafast measurements on the blue
      side of the inhomogeneous distribution of the oxazine dye Nile Blue. Under these
      conditions, a new form of interference was observed as a sinusoidal variation of
      the DFWM signal versus delay time. A measured interference period of 1.96+/-0.07
      fs corresponds to the optical cycle time of the light source. Numerical solutions
      for the DFWM intensity confirm the oscillation effect and estimate a measured
      dephasing time of 2-3 fs.

PMID- 18084598
TI  - Solitonlike pulse shortening in a femtosecond parametric amplifier.
AB  - We demonstrate numerically that simultaneous second-harmonic generation and
      moderate group-velocity mismatch can lead to spontaneous nonlinear shortening
      during parametric amplification. As an experimental proof we present the results
      of twofold self-compression of signal pulses in a beta-barium borate parametric
      amplifier pumped by either 40- or 80-fs pulses from a Ti:sapphire laser.

PMID- 18084599
TI  - Parametric generation of high-energy 14.5-fs light pulses at 1.5 mum.
AB  - High-energy light pulses that are tunable from 1.1 to 2.6 mum, with a duration as
      short as 14.5 fs were generated in a type II phase-matching beta-BaB(2)O(4)
      traveling-wave parametric converter pumped by 18-fs pulses obtained from a
      Ti:sapphire laser with chirped-pulse amplification, followed by a hollow-fiber
      compressor.

PMID- 18084600
TI  - Diffractive phase elements that synthesize color pseudo-nondiffracting beams.
AB  - The design of diffractive phase elements (DPE's) for generating color pseudo
      nondiffracting beams (PNDB's) in a multiple-wave illuminating system by the
      conjugate-gradient method is described. The axial-intensity distributions for
      dual-color PNDB's generated by the DPE's are shown. The color PNDB's behave as
      segmented axial-intensity distributions; in each of segments only one color
      persists. The sequence of wavelength components in the color PNDB's can be
      arbitrarily preset. Three-dimensional plots of a dual-color PNDB indicate the
      characteristics of a beam with high transverse resolution.

PMID- 18084601
TI  - Demonstration of real-time address header decoding for optical data routing at
      1536nm.
AB  - We have demonstrated real-time decoding of 20-bit biphase-coded address header
      pulses, using stimulated photon echoes in a phase-matched crossed-beam
      configuration. This decoding is one of the functions required for coherent
      transient optical data routing, packet switching, and processing. The active
      medium used was single-crystal Y(2)SiO(5) doped with Er(3+), which provides an
      operating wavelength of 1536 nm.

PMID- 18084602
TI  - Laser cooling of a solid by 21K starting from room temperature.
AB  - A fluorozirconate glass doped with trivalent ytterbium ions has been laser cooled
      in vacuo from 298 to 277 K by optical pumping of the ions at 1015 nm. The cooling
      effect arises from anti-Stokes fluorescence of the laser-excited ions and by
      virtue of the near-unit fluorescence quantum efficiency for Yb(3+) in
      sufficiently pure solid hosts. The sample temperatures in the experiment are
      determined by measurement of the Yb(3+) emission spectrum; the value of the
      observed temperature change from room temperature as a function of pump
      wavelength is successfully explained in terms of a simple two-level model that
      includes the effect of optical saturation.

PMID- 18084603
TI  - Investigation of the holographic storage capacity of paraelectric K(1-x)Lix Ta(1
      y) Nby O(3):Cu,V.
AB  - High holographic storage capacity of paraelectric K(1-x)Lix Ta(1-y) Nby O(3):Cu ,
      V using the voltage-controlled photorefractive effect is experimentally
      demonstrated. Measurements of the M/# for various writing angles and reading
      fields are presented. In particular, it is shown that 128 angularly multiplexed
      holograms, written by two plane-wave beams separated by an angle of 8 degrees ,
      yield an M/# of 20.

PMID- 18084604
TI  - Aberration-correction results from a segmented microelectromechanical deformable
      mirror and a refractive lenslet array.
AB  - Quadratic aberration is successfully corrected with a segmented
      microelectromechanical deformable mirror in conjunction with a refractive lenslet
      array. Use of the lenslet array greatly improves the effective fill factor of the
      correcting element. Experimental results show correction approaching the
      diffraction limit for an extreme spherical aberration.

PMID- 18084605
TI  - Three-dimensional photoacoustic imaging of blood vessels in tissue.
AB  - We applied photoacoustics as a tissue tomography technique for the detection of
      blood concentrations, e.g., angiogenesis around tumors. We imaged blood vessels
      in highly scattering samples, using 532-nm light, to depths of ~1 cm . The
      samples were real tissue (chicken breast) or 10% dilutions of Intralipid-10%. The
      blood flowed through nylon capillaries. Polyvinylidene difluoride (PVdF)
      piezoelectric detectors were used in a surface-scanning mode. We demonstrate the
      sensitivity of the technique by photoacoustic detection of single red blood cells
      upon a glass plate. Lateral resolution is limited by the detector diameter (200
      microm). The depth resolution is ~10 microm.

PMID- 18084607
TI  - A feasibility study evaluating the functional diffusion map as a predictive
      imaging biomarker for detection of treatment response in a patient with
      metastatic prostate cancer to the bone.
AB  - Prostate cancer (PCa) is the most commonly diagnosed cancer in American men with
      a subset inevitably presenting with metastatic disease to the bone. A well
      recognized limitation in evaluating new treatments for metastatic PCa is the
      inability to use imaging to objectively assess response therapy. In this study,
      we evaluated the feasibility of clinically translating the functional diffusion
      map (fDM) imaging biomarker for quantifying the spatiotemporal effects of bone
      tumor response in a patient treated for metastatic PCa with bone metastases. A
      patient beginning therapy was scanned using MRI before treatment and again at 2
      and 8 weeks post-treatment initiation to quantify changes in tumor diffusion
      values. Three metastatic lesions were identified for fDM analysis, all of which
      all demonstrated an early increase in diffusion values at 2 weeks, which
      increased further at 8 weeks post-treatment initiation. This finding correlated
      with a decrease in the patient's prostate-specific antigen (PSA) levels
      suggestive of patient response. CT, bone scans, and anatomic MRI images obtained
      posttreatment were found to be uninformative for the assessment of treatment
      effectiveness. This study presents the feasibility of fDM-measurements in osseous
      lesions over time and shows that changes in fDM values were consistent with
      therapeutic response. Thus, the fDM imaging biomarker may provide a quantifiable
      therapeutic endpoint to assess response in patients with metastatic bone cancer.

PMID- 18084608
TI  - RNA interference of interferon regulatory factor-1 gene expression in THP-1 cell
      line leads to Toll-like receptor-4 overexpression/activation as well as up
      modulation of annexin-II.
AB  - Interferon regulatory factor-1 (IRF-1) is a candidate transcription factor for
      the regulation of the Toll-like receptor-4 (TLR-4) gene. Using a small
      interfering RNA-based (siRNA) process to silence IRF-1 gene expression in the
      leukemic monocytic cell line THP-1, we investigated whether such a modulation
      would alter TLR-4 expression and activation status in these cells. The siIRF-1
      cells expressed elevated levels of TLR-4 mRNA and protein compared to controls by
      90% and 77%, respectively. ICAM.1 protein expression and apoptosis levels were
      increased by 8.35- and 4.25-fold, respectively. The siIRF-1 cells overexpressed
      Bax mRNA compared to controls. Proteomic analysis revealed upmodulation of the
      Annexin-II protein in siIRF-1 THP-1 cells. Myelodysplastic syndrome (MDS)
      patients with an absence of full-length IRF-1 mRNA also overexpressed Annexin-II.
      It is plausible that this overexpression may lead to the activation of TLR-4
      contributing to the increased apoptosis characterizing MDS.

PMID- 18084609
TI  - In vivo molecular imaging to diagnose and subtype tumors through receptor
      targeted optically labeled monoclonal antibodies.
AB  - Molecular imaging of cell surface receptors can potentially diagnose tumors based
      on their distinct expression profiles. Using multifilter spectrally resolved
      optical imaging with three fluorescently labeled antibodies, we simultaneously
      imaged three different cell surface receptors to distinguish tumor types
      noninvasively. We selected tumors overexpressing different subtypes of EGFR
      receptor: HER-1 (A431) and HER-2 (NIH3T3/HER2(+)), or interleukin-2 receptor
      alpha-subunit receptor (IL-2Ralpha; SP2/Tac). After tumor establishment, a
      cocktail of three fluorescently labeled monoclonal antibodies was injected:
      cetuximab-Cy5 (targetingHER-1), trastuzumab-Cy7(HER-2),anddaclizumab-AlexaFluor
      700 (IL-2Ra). Optical fluorescence imaging was performed after 24 hours with both
      a red filter set and three successive filter sets (yellow, red, and deep red).
      Spectrally resolved imaging of 10 mice clearly distinguished A431,
      NIH3T3/HER2(+), and SP2-Tac tumors based on their distinct optical spectra. Three
      filter sets significantly increased the signal-to-background ratio compared to a
      single-filter set by reducing the background signal, thus significantly improving
      the differentiation of each of the receptors targeted (P < .022). In conclusion,
      following multifilter spectrally resolved imaging, different tumor types can be
      simultaneously distinguished and diagnosed in vivo. Multiple filter sets increase
      the signal-to-noise ratio by substantially reducing the background signal, and
      may allow more optical dyes to be resolved within the narrow limits of the near
      infrared spectrum.

PMID- 18084610
TI  - In vivo evaluation of AT-101 (R-(-)-gossypol acetic acid) in androgen-independent
      growth of VCaP prostate cancer cells in combination with surgical castration.
AB  - PURPOSE: Upregulation of Bcl-2 family members is a well-established mechanism in
      the development of androgen-independent prostate cancer. Inhibition of the
      antiapoptotic proteins Bcl-2 and Mcl-1 may delay the transition to androgen
      independent growth. EXPERIMENTAL DESIGN: We have established a prostate cancer
      model with VCaP prostate cancer cells in vivo to study the transition to androgen
      independence. Here, we investigated the efficacy of AT-101 (R-(-)-gossypol acetic
      acid; a pan small molecule inhibitor of Bcl-2, Bcl-x(L), and Mcl-1) in
      combination with surgical castration to delay the onset of androgen-independent
      growth in vivo. RESULTS: AT-101 (15 mg/kg, per os (p.o.) 5 days/week) in
      combination with surgical castration delayed the onset of androgen-independent
      prostate cancer growth in vivo. In addition, we demonstrate the induction of
      caspase-9-and caspase-3-dependent induction of apoptosis following AT-101
      treatment in vitro which was accompanied by an AT-101-induced downregulation of
      Bcl-2 and Mcl-1 mRNA and protein expression. CONCLUSIONS: We conclude that AT-101
      in combination with surgical castration delays the onset of androgen-independent
      prostate cancer in vivo by disrupting the antiapoptotic activity of Bcl-2
      upregulation during the transition to androgen independence. Further studies are
      needed to define the mechanism of action by which AT-101 attenuates the
      expression of Bcl-2 and Mcl-1 and to characterize the potential for AT-101 in
      combination with hormone therapy.

PMID- 18084611
TI  - Differential gene expression of primary cultured lymphatic and blood vascular
      endothelial cells.
AB  - Blood vascular endothelial cells (BECs) and the developmentally related lymphatic
      endothelial cells (LECs) create complementary, yet distinct vascular networks.
      Each endothelial cell type interacts with flowing fluid and circulating cells,
      yet each vascular system has evolved specialized gene expression programs and
      thus both cell types display different phenotypes. BECs and LECs express distinct
      genes that are unique to their specific vascular microenvironment. Tumors also
      take advantage of the molecules that are expressed in these vascular systems to
      enhance their metastatic potential. We completed transcriptome analyses on
      primary cultured LECs and BECs, where each comparative set was isolated from the
      same individual. Differences were resolved in the expression of several major
      categories, such as cell adhesion molecules (CAMs), cytokines, and cytokine
      receptors. We have identified new molecules that are associated with BECs (e.g.,
      claudin-9, CXCL11, neurexin-1, neurexin-2, and the neuronal growth factor
      regulator-1) and LECs (e.g., claudin-7, CD58, hyaluronan and proteoglycan link
      protein 1 (HAPLN1), and the poliovirus receptor-related 3 molecule) that may lead
      to novel therapeutic treatments for diseases of lymphatic or blood vessels,
      including metastasis of cancer to lymph nodes or distant organs.

PMID- 18084612
TI  - Magnetic resonance imaging detection of tumor cells by targeting low-density
      lipoprotein receptors with Gd-loaded low-density lipoprotein particles.
AB  - Gd-DO3A-diph and Gd-AAZTAC17 are lipophilic magnetic resonance imaging (MRI)
      agents that display high affinity for low-density lipoprotein (LDL) particles.
      However, on binding to LDL, Gd-DO3A-diph shows a decreased hydration that results
      in a lower enhancement of water proton relaxation rate. Conversely, Gd-AAZTAC17
      displays a strong relaxation enhancement at the imaging fields. Each LDL particle
      can load up to 100 and 400 UNITS of Gd-DO3A-diph and Gd-AAZTAC17, respectively.
      Their LDL adducts are taken up by human hepatoblastoma G2 (HepG2) and melanoma
      B16 tumor cells when added to the incubation medium. T(1) measurements of the
      labeled cells indicate that Gd-AAZTAC17 is significantly more efficient than Gd
      DO3A-diph. Furthermore, it has been found that HepG2 hepatoma cells can
      internalize higher amounts of Gd-AAZTAC17 than B16 cells and the involvement of
      LDL receptors (LDLRs) has been demonstrated in competition assays with free LDL.
      Gd-AAZTAC17/LDL adduct proved to be an efficient probe in the magnetic resonance
      (MR) visualization of subcutaneous tumors in animal models obtained by injecting
      B16 melanoma cells into the right flank of mice. Finally, confocal microscopy
      validation of the distribution of LDL-based probes in the tumor has been obtained
      by doping the Gd-AAZTAC17/LDL adduct with a fluorescent phospholipid moiety.

PMID- 18084613
TI  - The contribution of transactivation subdomains 1 and 2 to p53-induced gene
      expression is heterogeneous but not subdomain-specific.
AB  - Two adjacent regions within the transactivation domain of p53 are sufficient to
      support sequence-specific transactivation when fused to a heterologous DNA
      binding domain. It has been hypothesized that these two subdomains of p53 may
      contribute to the expression of distinct p53-responsive genes. Here we have used
      oligonucleotide microarrays to identify transcripts induced by variants of p53
      with point mutations within subdomains 1, 2, or 1 and 2 (QS1, QS2, and QS1/QS2,
      respectively). The expression of 254 transcripts was increased in response to
      wild-type p53 expression but most of these transcripts were poorly induced by
      these variants of p53. Strikingly, a number of known p53-regulated transcripts
      including TNFRSF10B, BAX, BTG2, and POLH were increased to wild-type levels by
      p53(QS1) and p53(QS2) but not p53(QS1/QS2), indicating that either subdomain 1 or
      2 is sufficient for p53-dependent expression of a small subset of p53-responsive
      genes. Unexpectedly, there was no evidence for p53(QS1)- or p53(QS2)-specific
      gene expression. Taken together, we found heterogeneity in the requirement for
      transactivation subdomains 1 and 2 of p53 without any subdomain-specific
      contribution to p53-induced gene expression.

PMID- 18084614
TI  - Inhibition of epidermal growth factor receptor and vascular endothelial growth
      factor receptor phosphorylation on tumor-associated endothelial cells leads to
      treatment of orthotopic human colon cancer in nude mice.
AB  - The purpose of our study was to determine whether the dual inhibition of
      epidermal growth factor receptor (EGFR) and vascular endothelial growth factor
      receptor (VEGFR) signaling pathways in tumor-associated endothelial cells can
      inhibit the progressive growth of human colon carcinoma in the cecum of nude
      mice. SW620CE2 human colon cancer cells growing in culture and orthotopically in
      the cecum of nude mice expressed a high level of transforming growth factor alpha
      (TGF-alpha) and vascular endothelial growth factor (VEGF) but were negative for
      EGFR, human epidermal growth factor receptor 2 (HER2), and VEGFR. Double
      immunofluorescence staining revealed that tumor-associated endothelial cells
      expressed EGFR, VEGFR2, phosphorylated EGFR (pEGFR), and phosphorylated VEGFR
      (pVEGFR). Treatment of mice with either 7H-pyrrolo [2,3-d]-pyrimidine lead
      scaffold (AEE788; an inhibitor of EGFR and VEGFR tyrosine kinase) or CPT-11 as
      single agents significantly inhibited the growth of cecal tumors (P < .01); this
      decrease was even more pronounced with AEE788 combined with CPT-11 (P < .001).
      AEE788 alone or combined with CPT-11 also inhibited the expression of pEGFR and
      pVEGFR on tumor-associated endothelial cells, significantly decreased
      vascularization and tumor cell proliferation, and increased the level of
      apoptosis in both tumor-associated endothelial cells and tumor cells. These data
      demonstrate that targeting EGFR and VEGFR signaling on tumor-associated
      endothelial cells provides a viable approach for the treatment of colon cancer.

PMID- 18084615
TI  - Statins stimulate in vitro membrane FasL expression and lymphocyte apoptosis
      through RhoA/ROCK pathway in murine melanoma cells.
AB  - The capacity of FasL molecules expressed on melanoma cells to induce lymphocyte
      apoptosis contributes to either antitumor immune response or escape depending on
      their expression level. Little is known, however, about the mechanisms regulating
      FasL protein expression. Using the murine B16F10 melanoma model weakly positive
      for FasL, we demonstrated that in vitro treatment with statins, inhibitors of 3
      hydroxy-3-methylgutaryl CoA reductase, enhances membrane FasL expression. C3
      exotoxin and the geranylgeranyl transferase I inhibitor GGTI-298, but not the
      farnesyl transferase inhibitor FTI-277, mimic this effect. The capacity of GGTI
      298 and C3 exotoxin to inhibit RhoA activity prompted us to investigate the
      implication of RhoA in FasL expression. Inhibition of RhoA expression by small
      interfering RNA (siRNA) increased membrane FasL expression, whereas
      overexpression of constitutively active RhoA following transfection of RhoAV14
      plasmid decreased it. Moreover, the inhibition of a RhoA downstream effector
      p160ROCK also induced this FasL overexpression. We conclude that the RhoA/ROCK
      pathway negatively regulates membrane FasL expression in these melanoma cells.
      Furthermore, we have shown that B16F10 cells, through the RhoA/ROCK pathway,
      promote in vitro apoptosis of Fas-sensitive A20 lymphoma cells. Our results
      suggest that RhoA/ROCK inhibition could be an interesting target to control FasL
      expression and lymphocyte apoptosis induced by melanoma cells.

PMID- 18084616
TI  - IGFBP3 promoter methylation in colorectal cancer: relationship with
      microsatellite instability, CpG island methylator phenotype, and p53.
AB  - Insulin-like growth factor binding protein 3 (IGFBP3), which is induced by wild
      type p53, regulates IGF and interacts with the TGF-beta pathway. IGFBP3 promoter
      methylation may occur in colorectal cancer with or without the CpG island
      methylator phenotype (CIMP), which is associated with microsatellite instability
      (MSI) and TGFBR2 mutation. We examined the relationship between IGFBP3
      methylation, p53 expression, CIMP and MSI in 902 population-based colorectal
      cancers. Utilizing real-time PCR (MethyLight), we quantified promoter methylation
      in IGFBP3 and eight other CIMP-high-specific promoters (CACNA1G, CDKN2A, CRABP1,
      IGF2, MLH1, NEUROG1, RUNX3, and SOCS1). IGFBP3 methylation was far more frequent
      in non-MSI-high CIMP-high tumors (85% = 35/41) than in MSI-high CIMP-high (49% =
      44/90, P < .0001), MSI-high non-CIMP-high (17% = 6/36, P < .0001), and non-MSI
      high non-CIMP-high tumors (22% = 152/680, P < .0001). Among CIMP-high tumors, the
      inverse relationship between MSI and IGFBP3 methylation persisted in p53-negative
      tumors (P < .0001), but not in p53-positive tumors. IGFBP3 methylation was
      associated inversely with TGFBR2 mutation in MSI-high non-CIMP-high tumors (P =
      .02). In conclusion, IGFBP3 methylation is inversely associated with MSI in CIMP
      high colorectal cancers, and this relationship is limited to p53-negative tumors.
      Our data suggest complex relationship between global genomic/epigenomic phenomena
      (such as MSI/CIMP), single molecular events (e.g., IGFBP3 methylation, TP53
      mutation, and TGFBR2 mutation), and the related pathways.

PMID- 18084617
TI  - Internalization, intracellular trafficking, and biodistribution of monoclonal
      antibody 806: a novel anti-epidermal growth factor receptor antibody.
AB  - Overexpression of the epidermal growth factor receptor (EGFR) in epithelial
      tumors is associated with poor prognosis and is the target for a number of cancer
      therapeutics. Monoclonal antibody (mAb) 806 is a novel anti-EGFR antibody with
      significant therapeutic efficacy in tumor models when used as a single agent, and
      displays synergistic antitumor activity in combination with other EGFR
      therapeutics. Unlike other EGFR antibodies, mAb 806 is selective for tumor cells
      and does not bind to normal tissue, making it an ideal candidate for generation
      of radioisotope or toxin conjugates. Ideally, antibodies suited to these
      therapeutic applications must bind to and actively internalize their cognate
      receptor. We investigated the intracellular trafficking of fluorescently tagged
      mAb 806 in live cells and analyzed its biodistribution in a tumor xenografted
      nude mouse model. Following binding to EGFR, mAb 806 was internalized through
      dynamin-dependent, clathrin-mediated endocytosis. Internalized mAb 806 localized
      to early endosomes and subsequently trafficked to and accumulation in lysosomal
      compartments. Furthermore, biodistribution analysis in nude mice showed specific
      uptake and retention of radiolabeled mAb 806 to human tumor xenografts. These
      results highlight the potential use of mAb 806 for generation of conjugates
      suitable for diagnostic and therapeutic use in patients with EGFR-positive
      malignancies.

PMID- 18084618
TI  - Oxidative stress modulates DNA methylation during melanocyte anchorage blockade
      associated with malignant transformation.
AB  - Both oxidative/nitrosative stress and alterations in DNA methylation are observed
      during carcinogenesis of different tumor types, but no clear correlation between
      these events has been demonstrated until now. Melanoma cell lines were previously
      established after submitting the nontumorigenicmelanocyte lineage, melan-a, to
      cycles of anchorage blockade. In this work, increased intracellular oxidative
      species and nitric oxide levels, as well as alterations in the DNA methylation,
      were observed after melan-a detachment, which were also associated with a
      decrease in intracellular homocysteine (Hcy), an element in the methionine
      (universal methyl donor) cycle. This alteration was accompanied by increase in
      glutathione (GSH) levels and methylated DNA content. Furthermore, a significant
      increase in dnmt1 and 3b expression was identified along melan-a anchorage
      blockade. L(G)-Nitro-L-arginine methyl esther (L-NAME), known as a nitric oxide
      synthase (NOS) inhibitor, and N-acetyl-L-cysteine (NAC) prevented the increase in
      global DNA methylation, as well as the increase in dnmt1 and 3b expression,
      observed during melan-a detachment. Interestingly, both L-NAME and NAC did not
      inhibit nitric oxide (NO) production in these cells, but abrogated superoxide
      anion production during anchorage blockade. In conclusion, oxidative stress
      observed during melanocyte anchorage blockade seems to modulate DNA methylation
      levels and may directly contribute to the acquisition of an anoikis-resistant
      phenotype through an epigenetic mechanism.

PMID- 18084619
TI  - Effects of recombinant erythropoietin on breast cancer-initiating cells.
AB  - BACKGROUND: Cancer anemia causes fatigue and correlates with poor treatment
      outcome. Erythropoietin has been introduced in an attempt to correct these
      defects. However, five recent clinical trials reported a negative impact of
      erythropoietin on survival and/or tumor control, indicating that experimental
      evaluation of a possible direct effect of erythropoietin on cancer cells is
      required. Cancer recurrence is thought to rely on the proliferation of cancer
      initiating cells (CICs). In breast cancer, CICs can be identified by phenotypic
      markers and their fate is controlled by the Notch pathway. METHODS: In this
      study, we investigated the effect of erythropoietin on CICs in breast cancer cell
      lines. Levels of erythropoietin receptor (EpoR), CD24, CD44, Jagged-1 expression,
      and activation of Notch-1 were assessed by flow cytometry. Self-renewing capacity
      of CICs was investigated in sphere formation assays. RESULTS: EpoR expression was
      found on the surface of CICs. Recombinant human Epo (rhEpo) increased the numbers
      of CICs and self-renewing capacity in a Notch-dependent fashion by induction of
      Jagged-1. Inhibitors of the Notch pathway and PI3-kinase blocked both effects.
      CONCLUSIONS: Erythropoietin functionally affects CICs directly. Our observation
      may explain the negative impact of recombinant Epo on local control and survival
      of cancer patients with EpoR-positive tumors.

PMID- 18084620
TI  - Tracking the migration of dendritic cells by in vivo optical imaging.
AB  - We report herein a method to track the migration of dendritic cells (DCs) using
      optical imaging. With the assistance of the delivery module, fluorescein
      isothiocyanate (FITC) could internalize inside DCs within 15 minutes of
      incubation. The fluorescent signal was mostly cytoplasmic and could be detected
      using in vivo imaging. Furthermore, we observed that the probe did not interfere
      with the DCs maturation as we assessed the expression of several surface markers.
      The labeled DCs secreted interleukin-12 (IL-12) and tumor necrosis factor-alpha
      (TNF-alpha) and stimulated the proliferation of CD4+ T lymphocytes responding to
      lipopolysaccharide (LPS) stimulation. We have systematically compared the probe
      uptake between mature and immature DCs. The study showed that the latter
      phagocytosed the probe slightly better than the former. Intravital imaging of
      treated mice showed the migration of DCs to lymph nodes (LNs), which is confirmed
      by immunohistochemistry. Taken together, we demonstrated the potential use of
      optical imaging for tracking the migration of DCs and homing in vivo. The
      delivery molecules could also be used on other imaging modalities or for delivery
      of antigens.

PMID- 18084621
TI  - Hypoxia and the presence of human vascular endothelial cells affect prostate
      cancer cell invasion and metabolism.
AB  - Tumor progression and metastasis are influenced by hypoxia, as well as by
      interactions between cancer cells and components of the stroma, such as
      endothelial cells. Here, we have used a magnetic resonance (MR)-compatible
      invasion assay to further understand the effects of hypoxia on human prostate
      cancer cell invasion and metabolism in the presence and absence of human
      umbilical vein endothelial cells (HUVECs). Additionally, we compared endogenous
      activities of selected proteases related to invasion in PC-3 cells and HUVECs,
      profiled gene expression of PC-3 cells by microarray, and evaluated cell
      proliferation of PC-3 cells and HUVECs by flow cytometry, under hypoxic and
      oxygenated conditions. The invasion of less-invasive DU-145 cells was not
      affected by either hypoxia or the presence of HUVECs. However, hypoxia
      significantly decreased the invasion of PC-3 cells. This hypoxia-induced decrease
      was attenuated by the presence of HUVECs, whereas under oxygenated conditions,
      HUVECs did not alter the invasion of PC-3 cells. Cell metabolism changed
      distinctly with hypoxia and invasion. The endogenous activity of selected
      extracellular proteases, although altered by hypoxia, did not fully explain the
      hypoxia-induced changes in invasion. Gene expression profiling indicated that
      hypoxia affects multiple cellular functions and pathways.

PMID- 18084623
TI  - Utility of a new bolus-injectable nanoparticle for clinical cancer staging.
AB  - BACKGROUND: In this study, we report on the use of a new, bolus-injectable,
      carboxymethyl dextran-based magnetic nanoparticle (MNP), ferumoxytol, to improve
      detection in loco-regional lymph nodes by magnetic resonance imaging (MRI).
      METHODS: This preliminary study was performed as a prospective, single-center,
      open label pilot study to determine the magnitude of nodal MRI signal changes and
      to determine the optimal time points for imaging following intravenous (IV) bolus
      injection of the MNP. The study group consisted of 10 patients, all of whom were
      diagnosed with prostate cancer before any systemic therapy. RESULTS: All 10
      patients had lymph nodes evaluated by histopathology. Of the evaluated 26 lymph
      nodes, 20 were benign and 6 were malignant. The mean short-axis diameter of
      benign lymph nodes was 6 mm and the mean short-axis diameter of malignant lymph
      nodes was 7 mm. Following IV administration, there was a significant change in
      mean signal-to-noise ratio (SNR) of benign lymph nodes (P < .0001) whereas there
      was little change in the mean SNR of malignant nodes (P = .1624). No adverse
      events were encountered. CONCLUSION: Ferumoxytol is safe and, at the appropriate
      circulation interval, modulates nodal signal intensity, allowing for
      identification of malignant nodal involvement by MRI.

PMID- 18084624
TI  - A parallel implementation of the Cellular Potts Model for simulation of cell
      based morphogenesis.
AB  - The Cellular Potts Model (CPM) has been used in a wide variety of biological
      simulations. However, most current CPM implementations use a sequential modified
      Metropolis algorithm which restricts the size of simulations. In this paper we
      present a parallel CPM algorithm for simulations of morphogenesis, which includes
      cell-cell adhesion, a cell volume constraint, and cell haptotaxis. The algorithm
      uses appropriate data structures and checkerboard subgrids for parallelization.
      Communication and updating algorithms synchronize properties of cells simulated
      on different processor nodes. Tests show that the parallel algorithm has good
      scalability, permitting large-scale simulations of cell morphogenesis (10(7) or
      more cells) and broadening the scope of CPM applications. The new algorithm
      satisfies the balance condition, which is sufficient for convergence of the
      underlying Markov chain.

PMID- 18084622
TI  - Expression of androgen receptor is negatively regulated by p53.
AB  - Increased expression of androgen receptor (AR) in prostate cancer (PC) is
      associated with transition to androgen independence. Because the progression of
      PC to advanced stages is often associated with the loss of p53 function, we
      tested whether the p53 could regulate the expression of AR gene. Here we report
      that p53 negatively regulates the expression of AR in prostate epithelial cells
      (PrECs). We found that in LNCaP human prostate cancer cells that express the wild
      type p53 and AR and in human normal PrECs, the activation of p53 by genotoxic
      stress or by inhibition of p53 nuclear export downregulated the expression of AR.
      Furthermore, forced expression of p53 in LNCaP cells decreased the expression of
      AR. Conversely, knockdown of p53 expression in LNCaP cells increased the AR
      expression. Consistent with the negative regulation of AR expression by p53, the
      p53-null HCT116 cells expressed higher levels of AR compared with the isogenic
      HCT116 cells that express the wildtype p53. Moreover, we noted that in etoposide
      treated LNCaP cells p53 bound to the promoter region of the AR gene, which
      contains a potential p53 DNA-binding consensus sequence, in chromatin
      immunoprecipitation assays. Together, our observations provide support for the
      idea that the loss of p53 function in prostate cancer cells contributes to
      increased expression of AR.

PMID- 18084625
TI  - Influence of Student-Teacher and Parent-Teacher Relationships on Lower Achieving
      Readers' Engagement and Achievement in the Primary Grades.
AB  - Participants were 443 (52.6% male, 47.4% female) ethnically diverse, 1st-grade,
      lower achieving readers attending 1 of 3 school districts in Texas. Using latent
      variable structural equation modeling, the authors tested a theoretical model
      positing that (a) the quality of teachers' relationships with students and their
      parents mediates the associations between children's background characteristics
      and teacher-rated classroom engagement and that (b) child classroom engagement,
      in turn, mediates the associations between student-teacher and parent-teacher
      relatedness and child achievement the following year. The hypothesized model
      provided a good fit to the data. African American children and their parents,
      relative to Hispanic and Caucasian children and their parents, had less
      supportive relationships with teachers. These differences in relatedness may be
      implicated in African American children's lower achievement trajectories in the
      early grades. Implications of these findings for teacher preparation are
      discussed.

PMID- 18084626
TI  - Role of resilient personality on lower achieving first grade students' current
      and future achievement.
AB  - This study investigated a measurement model of personality resilience and the
      contribution of personality resilience to lower achieving first grade students'
      academic achievement. Participants were 445 ethnically diverse children who at
      entrance to first grade scored below their school district median on a test of
      literacy. Participants were administered an individual achievement test in first
      grade and 1 year later. Confirmatory factor analysis confirmed a second-order
      latent construct of resilient personality defined by teacher-rated
      conscientiousness, agreeableness, and ego-resiliency that was distinct from
      measures of externalizing behaviors and IQ. Using latent structural equation
      modeling and controlling for baseline economic adversity, IQ, and externalizing
      symptoms, resilient personality predicted children's concurrent and future
      achievement (controlling also for baseline achievement in the prospective
      analyses). Model fit was invariant across gender.

PMID- 18084627
TI  - Fiscal Shenanigans, Targeted Federal Health Care Funds, and Patient Mortality.
AB  - We explore the effectiveness of matching grants when lower levels of government
      can expropriate some of the funds for other uses. Using data on the Medicaid
      Disproportionate Share program, we identify states that were most able to
      expropriate funds. Payments to public hospitals in these states were
      systematically diverted and had no significant impact on patient mortality.
      Payments that were not expropriated were associated with significant declines in
      patient mortality. Overall, subsidies were an effective mechanism for improving
      outcomes for the poor, but the impact was limited by the ability of state and
      local governments to divert the targeted funds.

PMID- 18084628
TI  - Mapping rice field anopheline breeding habitats in Mali, West Africa, using
      Landsat ETM+ sensor data.
AB  - The aim of this study was to determine whether remotely sensed data could be used
      to identify rice-related malaria vector breeding habitats in an irrigated rice
      growing area near Niono, Mali. Early stages of rice growth show peak larval
      production, but Landsat sensor data are often obstructed by clouds during the
      early part of the cropping cycle (rainy season). In this study, we examined
      whether a classification based on two Landsat Enhanced Thematic Mapper (ETM)+
      scenes acquired in the middle of the season and at harvesting times could be used
      to map different land uses and rice planted at different times (cohorts), and to
      infer which rice growth stages were present earlier in the season. We performed a
      maximum likelihood supervised classification and evaluated the robustness of the
      classifications with the transformed divergence separability index, the kappa
      coefficient and confusion matrices. Rice was distinguished from other land uses
      with 98% accuracy and rice cohorts were discriminated with 84% accuracy (three
      classes) or 94% (two classes). Our study showed that optical remote sensing can
      reliably identify potential malaria mosquito breeding habitats from space. In the
      future, these 'crop landscape maps' could be used to investigate the relationship
      between cultivation practices and malaria transmission.

PMID- 18084629
TI  - A prototype of very high resolution small animal PET scanner using silicon pad
      detectors.
AB  - A very high resolution small animal positron emission tomograph (PET) which can
      achieve sub-millimeter spatial resolution is being developed using silicon pad
      detectors. The prototype PET for a single slice instrument consists of two 1 mm
      thick silicon pad detectors, each containing a 32 x 16 array of 1.4 mm x 1.4 mm
      pads read out with four VATAGP3 chips which have 128 channels low-noise self
      triggering ASIC in each chip, coincidence units, a source turntable and tungsten
      slice collimator. The silicon detectors were located edgewise on opposite sides
      of a 4 cm field-of-view to maximize efficiency. Energy resolution is dominated by
      electronic noise, which is 0.98% (1.38 keV) FWHM at 140.5 keV. Coincidence timing
      resolution is 82.1 ns FWHM and coincidence efficiency was measured to be 1.04 x
      10(-3) % from two silicon detectors with annihilation photons of (18)F source
      Image data were acquired and reconstructed using conventional 2-D filtered-back
      projection (FBP) and a maximum likelihood expectation maximization (ML-EM)
      method. Image resolution of approximately 1.45 mm FWHM is obtained from 1-D
      profile of 1.1 mm diameter (18)F line source image. Even better resolution can be
      obtained with smaller detector element sizes. While many challenges remain in
      scaling up the instrument to useful efficiency including densely packed detectors
      and significantly improved timing resolution, performance of the test setup in
      terms of easily achieving submillimeter resolution is compelling.

PMID- 18084631
TI  - Comparative analysis of Drosophila melanogaster and Caenorhabditis elegans gene
      expression experiments in the European Soyuz flights to the International Space
      Station.
AB  - The European Soyuz missions have been one of the main routes for conducting
      scientific experiments onboard the International Space Station, which is
      currently in the construction phase. A relatively large number of life and
      physical sciences experiments as well as technology demonstrations have been
      carried out during these missions. Included among these experiments are the Gene
      experiment during the Spanish "Cervantes" Soyuz mission and the ICE-1st
      experiment during the Dutch "Delta" mission. In both experiments, full genome
      microarray analyses were carried out on RNA extracted from whole animals
      recovered from the flight. These experiments indicated relatively large scale
      changes in gene expression levels in response to spaceflight for two popular
      model systems, Drosophila melanogaster (Gene) and Caenorabditis elegans (ICE
      1st). Here we report a comparative analysis of results from these two
      experiments. Finding orthologous genes between the fruit fly and the nematode was
      far from straightforward, reducing the number of genes that we could compare to
      roughly 20% of the full comparative genome. Within this sub-set of the data (2286
      genes), only six genes were found to display identical changes between species
      (decreased) while 1809 genes displayed no change in either species. Future
      experiments using ground simulation techniques will allow producing a better,
      more comprehensive picture of the putative set of genes affected in multicellular
      organisms by changes in gravity and getting a deeper understanding of how animals
      respond and adapt to spaceflight.

PMID- 18084632
TI  - Ethnicity and Language Contributions to Dimensions of Parent Involvement.
AB  - This study examined ethnic and language group differences on dimensions of parent
      rated and teacher-rated parent involvement after adjusting for the influence of
      family socioeconomic factors. A total of 179 teachers and 481 parents provided
      information on parent school involvement for a sample of ethnically and
      linguistically diverse first-grade children attending one of three school
      districts in Texas. Four groups were examined: White, Black, Hispanic-English
      speaking, and Hispanic-Spanish speaking. Exploratory and confirmatory factor
      analysis supported four parent-reported involvement dimensions (positive
      perceptions about school, communication, parent-teacher shared responsibility,
      and parent school-based involvement) and three teacher-reported dimensions
      (alliance, general parent involvement, and teacher initiation of involvement).
      Data generally supported the hypothesized ethnic and language group differences
      in parent involvement and the moderating effect of dimension of parent
      involvement on group differences. Implications for school psychologists are
      discussed.

PMID- 18084633
TI  - Use of a SQUID array to detect T-cells with magnetic nanoparticles in determining
      transplant rejection.
AB  - Acute rejection in organ transplant is signaled by the proliferation of T-cells
      that target and kill the donor cells requiring painful biopsies to detect
      rejection onset. An alternative non-invasive technique is proposed using a multi
      channel superconducting quantum interference device (SQUID) magnetometer to
      detect T-cell lymphocytes in the transplanted organ labeled with magnetic
      nanoparticles conjugated to antibodies specifically attached to lymphocytic
      ligand receptors. After a magnetic field pulse, the T-cells produce a decaying
      magnetic signal with a characteristic time of the order of a second. The extreme
      sensitivity of this technique, 10(5) cells, can provide early warning of
      impending transplant rejection and monitor immune-suppressive chemotherapy.

PMID- 18084634
TI  - Depressive Symptoms Among Delinquent Youth: Testing Models of Association with
      Stress and Support.
AB  - The high prevalence of depression among incarcerated youth indicates a need to
      better understand factors that contribute to depression within this vulnerable
      subgroup. Previous research in general community samples has suggested that high
      levels of stress and low levels of parental support are associated with
      depression in young people, but it is unclear whether or how they might be
      associated with depression among incarcerated youth who are already vulnerable.
      Using a sample of 228 adolescents (aged 13-18 years) who were detained in the
      juvenile justice system, stress and support were modeled as independent main
      effects and as interactive risk factors in relation to depressive symptoms. More
      stressful life events and less caregiver support were each independently
      associated with depressive symptoms, but no evidence was found for the buffering
      hypothesis in this sample. Stressful life events were more strongly associated
      with depressive symptoms among boys compared to girls.

PMID- 18084635
TI  - Age of Entry to Kindergarten and Children's Academic Achievement and
      Socioemotional Development.
AB  - RESEARCH FINDINGS: Data on more than 900 children participating in the National
      Institute of Child Health and Human Development Study of Early Child Care were
      analyzed to examine the effect of age of entry to kindergarten on children's
      functioning in early elementary school. Children's academic achievement and
      socioemotional development were measured repeatedly from the age of 54 months
      through 3rd grade. With family background factors and experience in child care in
      the first 54 months of life controlled, hierarchical linear modeling (growth
      curve) analysis revealed that children who entered kindergarten at younger ages
      had higher (estimated) scores in kindergarten on the Woodcock-Johnson (W-J)
      Letter-Word Recognition subtest but received lower ratings from kindergarten
      teachers on Language and Literacy and Mathematical Thinking scales. Furthermore,
      children who entered kindergarten at older ages evinced greater increases over
      time on 4 W-J subtests (i.e., Letter-Word Recognition, Applied Problems, Memory
      for Sentences, Picture Vocabulary) and outperformed children who started
      kindergarten at younger ages on 2 W-J subtests in 3rd grade (i.e., Applied
      Problems, Picture Vocabulary). Age of entry proved unrelated to socioemotional
      functioning. PRACTICE: The fact that age-of-entry effects were small in magnitude
      and dwarfed by other aspects of children's family and child care experiences
      suggests that age at starting school should not be regarded as a major
      determinant of children's school achievement, but that it may merit consideration
      in context with other probably more important factors (e.g., child's behavior and
      abilities).

PMID- 18084636
TI  - Long-Term Patterns and Predictors of Successful Stressor Resolution in Later
      Life.
AB  - At 1 year, 4 years, and 10 years after baseline, late-middle-aged adults reported
      whether they had successfully resolved their most important stressor of the past
      year. Compared to individuals who never resolved focal stressors over the 10-year
      interval, those who always did consistently showed less negative stressor
      appraisal, less reliance on avoidance coping, and less use of exploratory
      relative to directed coping responses, independent of type and severity of focal
      stressor. Less use of exploratory relative to directed coping and having more
      social resources, fewer health problems, and fewer depressive symptoms at
      baseline predicted more stressor resolution over the next 10 years. These
      predictors are promising foci for prospective efforts to optimize ways in which
      aging adults manage late-life stressors.

PMID- 18084637
TI  - Phylogenetic position of the ant genus Acropyga Roger (Hymenoptera: Formicidae)
      and the evolution of trophophoresy.
AB  - Trophophoresy is exhibited in two ant genera: Acropyga (Formicinae), in which all
      37 species are thought to be trophophoretic, and Tetraponera (Pseudomyrmecinae),
      in which it has been observed in only one species, T. binghami. This study
      analyses a dataset comprised of both morphological and molecular (D2 region of
      28S rRNA and EF1-alpha) data. Evidence is presented in favor of Acropyga being
      monophyletic, hence trophophoresy has evolved only once within the Formicinae and
      twice within the ants overall. The data further suggests that Acropyga belongs
      within a clade containing Anoplolepis, Aphomomyrmex, and Petalomyrmex.
      Aphomomyrmex and Petalomyrmex were found to be the sister group to Acropyga. The
      results indicate that the Lasiini and Plagiolepidini are not monophyletic and are
      in need of reexamination. Given the extant pantropical distribution of Acropyga
      it is speculated that Acropyga maybe of Gondwanan origin and that trophobiosis
      was the first form of agriculture to evolve in the ants.

PMID- 18084638
TI  - Twenty Years of Delila and Molecular Information Theory: The Altenberg-Austin
      Workshop in Theoretical Biology Biological Information, Beyond Metaphor:
      Causality, Explanation, and Unification Altenberg, Austria, 11-14 July 2002.
AB  - A brief personal history is given about how information theory can be applied to
      binding sites of genetic control molecules on nucleic acids. The primary example
      used is ribosome binding sites in Escherichia coli. Once the sites are aligned,
      the information needed to describe the sites can be computed using Claude
      Shannon's method. This is displayed by a computer graphic called a sequence logo.
      The logo represents an average binding site, and the mathematics easily allows
      one to determine the components of this average. That is, given a set of binding
      sites, the information for individual binding sites can also be computed. One can
      go further and predict the information of sites that are not in the original data
      set. Information theory also allows one to model the flexibility of ribosome
      binding sites, and this led us to a simple model for ribosome translational
      initiation in which the molecular components fit together only when the ribosome
      is at a good ribosome binding site. Since information theory is general, the same
      mathematics applies to human splice junctions, where we can predict the effect of
      sequence changes that cause human genetic diseases and cancer. The second example
      given is the Pribnow 'box' which, when viewed by the information theory method,
      reveals a mechanism for initiation of both transcription and DNA replication.
      Replication, transcription, splicing, and translation into protein represent the
      central dogma, so these examples show how molecular information theory is
      contributing to our knowledge of basic biology.

PMID- 18084641
TI  - Neuroendocrine immunity in patients with Alzheimer's disease: toward
      translational epigenetics.
AB  - The emerging domain of epigenetics in molecular medicine finds application for a
      variety of patient populations. Here, we present fundamental neuroendocrine
      immune evidence obtained in patients with senile dementia of the Alzheimer's type
      (sDAT), and discuss the implications of these data from the viewpoint of
      translational epigenetics of Alzheimer's disease. We followed 18 subjects with
      mild sDAT treated with acetylcholinesterase inhibitors, and 10 control subjects
      matched for age in a repeated measure design every six months for 18 months. We
      monitored psychosocial profile (Mini-Mental State Examination, Functional
      Assessment Staging, Independence in Activities of Daily Living, Depression,
      Profile of Moods States) in parallel to immunophenotypic parameters of T cell
      subpopulations by flow cytometry. Based on change in the mini-mental state score
      at entry and at 18 months, patients with sDAT were assigned to a "fast
      progression" (delta greater than 2 points) or to a "slow progression" group
      (delta less than or equal to 2 points). The change in circulating activated T
      cells (CD3+Dr+) with time in patients with sDAT was significantly inversely
      correlated with the change in time in natural killer (NK) cytotoxic activity to
      cortisol modulation in these patients, which was greater in patients with fast
      progression, compared to slow progression sDAT. These data indicate underlying
      neuroendocrine immune processes during progression of sDAT. Our observations
      suggest that psychoimmune measures such as those we have monitored in this study
      provide relevant information about the evolving physiological modulation in
      patients with sDAT during progression of Alzheimer's disease, and point to new or
      improved translational epigenetic treatment interventions.

PMID- 18084640
TI  - Immunological thresholds in neurological gene therapy: highly efficient
      elimination of transduced cells might be related to the specific formation of
      immunological synapses between T cells and virus-infected brain cells.
AB  - First-generation adenovirus can be engineered with powerful promoters to drive
      expression of therapeutic transgenes. Numerous clinical trials for glioblastoma
      multiforme using first generation adenoviral vectors have either been performed
      or are ongoing, including an ongoing, Phase III, multicenter trial in Europe and
      Israel (Ark Therapeutics, Inc.). Although in the absence of anti-adenovirus
      immune responses expression in the brain lasts 6-18 months, systemic infection
      with adenovirus induces immune responses that inhibit dramatically therapeutic
      transgene expression from first generation adenoviral vectors, thus, potentially
      compromising therapeutic efficacy. Here, we show evidence of an immunization
      threshold for the dose that generates an immune response strong enough to
      eliminate transgene expression from the CNS. For the systemic immunization to
      eliminate transgene expression from the brain, > or = 1 x 10(7) infectious units
      (iu) of adenovirus need to be used as immunogen. Furthermore, this immune
      response eliminates >90% of transgene expression from 1 x 10(7)-1 x 10(3) iu of
      vector injected into the striatum 60 days earlier. Importantly, elimination of
      transgene expression is independent of the nature of the promoter that drives
      transgene expression and is accompanied by brain infiltration of CD8(+) T cells
      and macrophages. In conclusion, once the threshold for systemic immunization
      (i.e. 1 x 10(7) iu) is crossed, the immune response eliminates transgene
      expression by >90% even from brains that receive as little as 1000 iu of
      adenoviral vectors, independently of the type of promoter that drives expression.

PMID- 18084642
TI  - Mfuzz: a software package for soft clustering of microarray data.
AB  - For the analysis of microarray data, clustering techniques are frequently used.
      Most of such methods are based on hard clustering of data wherein one gene (or
      sample) is assigned to exactly one cluster. Hard clustering, however, suffers
      from several drawbacks such as sensitivity to noise and information loss. In
      contrast, soft clustering methods can assign a gene to several clusters. They can
      overcome shortcomings of conventional hard clustering techniques and offer
      further advantages. Thus, we constructed an R package termed Mfuzz implementing
      soft clustering tools for microarray data analysis. The additional package
      Mfuzzgui provides a convenient TclTk based graphical user interface.
      AVAILABILITY: The R package Mfuzz and Mfuzzgui are available at
      http://itb1.biologie.hu-berlin.de/~futschik/software/R/Mfuzz/index.html. Their
      distribution is subject to GPL version 2 license.

PMID- 18084643
TI  - An insight into cyanobacterial genomics--a perspective.
AB  - At the turn of the millennium, cyanobacteria deserve attention to be reviewed to
      understand the past, present and future. The advent of post genomic research,
      which encompasses functional genomics, structural genomics, transcriptomics,
      pharmacogenomics, proteomics and metabolomics that allows a systematic wide
      approach for biological system studies. Thus by exploiting genomic and associated
      protein information through computational analyses, the fledging information that
      are generated by biotechnological analyses, could be well extrapolated to fill in
      the lacuna of scarce information on cyanobacteria and as an effort this paper
      attempts to highlights the perspectives available and awakens researcher to
      concentrate in the field of cyanobacterial informatics.

PMID- 18084644
TI  - Drug, dosage, activity, studies of antimalarials by physical methods--II.
AB  - Studies pertaining to drug-DNA interactions in treating a disease efficiently
      have taken an important place in recent times. Murthy and colleagues were active
      in correlating the drug activity, with physical parameters like refractivity,
      susceptibility, molecular electron ionization cross-section and the dosage. The
      molecular polarizability, diamagnetic susceptibility and molecular electron
      ionization cross section Q have been evaluated. An analysis of Q in the light of
      the data available on plasma protein binding, bio availability, Log P and half
      Life show semblance of regular dependence of Q on them and hence an effort is
      made to bring this dependence into a regular mathematical relationship. The
      dosage of each drug is calculated. A critical look at the results arrived on Q
      and dosages reveal that a highly active drug with large Q need to be monitored in
      very small quantities and any minute increase in dosage is resulting in unwanted
      toxic effects and vice versa. The algebraic formulae enable one to calculate the
      dosages theoretically from the value of Q and other parameters and the calculated
      dosage through the formulae agreed favorably well with suggested dosages. For
      example, in primaquine phosphate, the calculated dosage is 30 mg per day against
      the suggested practical dosage of 26.3 mg per day. A similar observation is made
      in mepacrine with theoretical dosage of 60 mg per day as against the suggested
      practical dosage of 100 mg per day. In short, the molecular structure followed by
      refraction and susceptibility measurements and Q will throw light on dosage,
      toxicity of a drug. Thus the present investigations pave way for a new direction
      of approach for study of drug activity without recourse to techniques involving
      highly expensive instrumentation and highly theoretical approaches involving
      quantum mechanical methods.

PMID- 18084639
TI  - Neuropharmacology of the endocannabinoid signaling system-molecular mechanisms,
      biological actions and synaptic plasticity.
AB  - The endocannabinoid signaling system is composed of the cannabinoid receptors;
      their endogenous ligands, the endocannabinoids; the enzymes that produce and
      inactivate the endocannabinoids; and the endocannabinoid transporters. The
      endocannabinoids are a new family of lipidic signal mediators, which includes
      amides, esters, and ethers of long-chain polyunsaturated fatty acids.
      Endocannabinoids signal through the same cell surface receptors that are targeted
      by Delta(9)-tetrahydrocannabinol (Delta(9)THC), the active principles of cannabis
      sativa preparations like hashish and marijuana. The biosynthetic pathways for the
      synthesis and release of endocannabinoids are still rather uncertain. Unlike
      neurotransmitter molecules that are typically held in vesicles before synaptic
      release, endocannabinoids are synthesized on demand within the plasma membrane.
      Once released, they travel in a retrograde direction and transiently suppress
      presynaptic neurotransmitter release through activation of cannabinoid receptors.
      The endocannabinoid signaling system is being found to be involved in an
      increasing number of pathological conditions. In the brain, endocannabinoid
      signaling is mostly inhibitory and suggests a role for cannabinoids as
      therapeutic agents in central nervous system (CNS) disease. Their ability to
      modulate synaptic efficacy has a wide range of functional consequences and
      provides unique therapeutic possibilities. The present review is focused on new
      information regarding the endocannabinoid signaling system in the brain. First,
      the structure, anatomical distribution, and signal transduction mechanisms of
      cannabinoid receptors are described. Second, the synthetic pathways of
      endocannabinoids are discussed, along with the putative mechanisms of their
      release, uptake, and degradation. Finally, the role of the endocannabinoid
      signaling system in the CNS and its potential as a therapeutic target in various
      CNS disease conditions, including alcoholism, are discussed.

PMID- 18084645
TI  - Computational and molecular characterization of multiple isoforms of lfe-2 gene
      in nematode C. elegans.
AB  - C. elegans C46H11.4 gene encodes a Let-23 fertility effector/regulator protein of
      the EGF-receptor class of the tyrosine kinase family. Alternative splicing is a
      major mechanism of generating protein diversity in higher eukaryotes. C. elegans
      genome sequencing consortium has reported three alternatively spliced transcripts
      of C46H11.4 gene which encodes for three hypothetical proteins namely, C46H11.4a,
      C46H11.4b and C46H11.4c. Using a combination of various bioinformatics tools like
      gene or exon finding programmes, blast searches, alignment tools etc followed by
      experimental validation, we report the presence of three more alternatively
      spliced transcripts which encode for novel hypothetical proteins C46H11.4d,
      C46H11.4e and C46H11.4f. These isoforms arise as a result of alternative splicing
      in the pre-mRNA encoded by gene C46H11.4. These novel un-reported spliced
      variants not only point towards the extent of alternative splicing in C. elegans
      genes but also hint towards the complex nature of alternative splicing.

PMID- 18084646
TI  - A database for medicinal plants used in the treatment of diabetes and its
      secondary complications.
AB  - Effective treatment of diabetes is increasingly dependent on active constituents
      of medicinal plants capable of controlling hyperglycemia as well as its secondary
      complications. Sensing the importance of documenting such medicinal plants, here
      we describe a web database containing information (name, literature citation,
      active compounds and few related full text articles) of the diabetes medicinal
      plants exhibiting hypoglycemic, antioxidant and antimicrobial effects.
      AVAILABILITY: http://www.autogeneralfilters.com/holycross/Home.html.

PMID- 18084647
TI  - Aluminium blunts the proliferative response and increases apoptosis of cultured
      human cells: putative relationship to Alzheimer's disease.
AB  - Aluminium (Al) has been investigated as a neurotoxic substance. Al ranks among
      the potential environmental risk factors for Alzheimer's disease (AD).
      Epidemiological studies tested the relationship between Al in drinking water and
      AD, showing a significant correlation between elevated levels of monomeric Al in
      water and AD, although data to date remain inconclusive with respect to total Al.
      The aim of this study was to test whether or not Al exacerbates cellular toxicity
      mediated by the amyloid beta (Abeta) peptide. We evaluated the role of Al in
      modulating programmed cell death (apoptosis) in human cell cultures. We used the
      osteosarcoma cell line monolayer (SaOs-2) to demonstrate that treatment of SaOs-2
      cultures with the Abeta peptide mid-fragment (25 to 35) at nano M, followed by co
      incubation with physiological concentrations of aluminium chloride, which release
      monomeric Al in solution, led to marked expression of caspase 3, but not caspase
      9, key markers of the apoptotic process. The same experimental conditions were
      shown to blunt significantly the proliferative response of normal human
      peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA)
      stimulation. Our observations support the hypothesis that Al significantly
      impairs certain cellular immune responses, and confirm that Al-mediated cell
      toxicity may play an important role in AD.

PMID- 18084648
TI  - HBNG: Graph theory based visualization of hydrogen bond networks in protein
      structures.
AB  - HBNG is a graph theory based tool for visualization of hydrogen bond network in
      2D. Digraphs generated by HBNG facilitate visualization of cooperativity and
      anticooperativity chains and rings in protein structures. HBNG takes hydrogen
      bonds list files (output from HBAT, HBEXPLORE, HBPLUS and STRIDE) as input and
      generates a DOT language script and constructs digraphs using freeware AT and T
      Graphviz tool. HBNG is useful in the enumeration of favorable topologies of
      hydrogen bond networks in protein structures and determining the effect of
      cooperativity and anticooperativity on protein stability and folding. HBNG can be
      applied to protein structure comparison and in the identification of secondary
      structural regions in protein structures. AVAILABILITY: Program is available from
      the authors for non-commercial purposes.

PMID- 18084649
TI  - Hypo, hype and 'hyp' human proteins.
AB  - Genes with unknown function are called orphan genes while their transcripts and
      peptides are called hypothetical proteins. There are many genes and their
      associated proteins that remain uncharacterized in the human genome. A database
      of human hypothetical proteins with ascribed functions could be helpful for
      biologists to search for potential proteins of interest. In recent years, the
      rapid completion of genome sequences has created essential information to link
      genes to gene products. In order to better explain functions for un-annotated
      proteins we designed BioinformaTRICKS (an open source project) and used it to
      develop a database called HYPO. AVAILABILITY: The database is available for free
      at http://pc-dugong.ruc.dk:8080.

PMID- 18084650
TI  - Current status of immunology research in India.
AB  - Rudimentary studies on aspects of biochemistry in India date back to 1927. But,
      in the field of Immunology, such studies were started by scholars only during
      early 1970s at the All India Institute of Medical Sciences, New Delhi, India.
      Science and Technology was not an immediate priority until 1961 due to domestic
      and political conditions in the country. We were then 11 years old since
      independence and our focus was on economic and social developments. Gradually,
      improvements were made in the field and now we have 15 to 20 major groups (small
      in size) of immunologists in the country, who have made significant contribution
      in the field during the last 8 to 10 years. Hence, we anticipate improvements in
      manpower and infrastructure in the near future.

PMID- 18084651
TI  - Oxytocin analogues with amide groups substituted by tetrazole groups in position
      4, 5 or 9.
AB  - Eleven oxytocin analogues substituted in position 4, 5 or 9 by tetrazole
      analogues of amino acids were prepared using solid-phase peptide synthesis method
      and tested for rat uterotonic in vitro and pressor activities, as well as for
      their affinity to human oxytocin receptor. The tetrazolic group has been used as
      a bioisosteric substitution of carboxylic, ester or amide groups in structure
      activity relationship studies of biologically active compounds. Replacement of
      the amide groups of Gln(4) and Asn(5) in oxytocin by tetrazole analogues of
      aspartic, glutamic and alpha-aminoadipic acids containing the tetrazole moiety in
      the side chains leads to analogues with decreased biological activities. Oxytocin
      analogues in which the glycine amide residue in position 9 was substituted by
      tetrazole analogues of glycine had diminished activities as well. The analysis of
      differences in rat uterotonic activity and in the affinity to human oxytocin
      receptors of analogues containing either an acidic 5-substituted tetrazolic group
      or a neutral 1,5- or 2,5-tetrazole nucleus makes it possible to draw some new
      conclusions concerning the role of the amide group of amino acids in positions 4,
      5 and 9 of oxytocin for its activity. The data suggest that the interaction of
      the side chain of Gln(4) with the oxytocin receptor is influenced mainly by
      electronic effects and the hydrogen bonding capacity of the amide group. Steric
      effects of the side chain are minor. Substitution of Asn(5) by its tetrazole
      derivative gave an analogue of very low activity. The result suggests that in the
      interaction between the amide group of Asn(5) and the binding sites of oxytocic
      receptor hydrogen bonds are of less importance than the spatial requirements for
      this group.

PMID- 18084652
TI  - Metabolic transformations of antitumor imidazoacridinone, C-1311, with microsomal
      fractions of rat and human liver.
AB  - The imidazoacridinone derivative C-1311 is an antitumor agent in Phase II
      clinical trials. The molecular mechanism of enzymatic oxidation of this compound
      in a peroxidase model system was reported earlier. The present studies were
      performed to elucidate the role of rat and human liver enzymes in metabolic
      transformations of this drug. C-1311 was incubated with different fractions of
      liver cells and the reaction mixtures were analyzed by RP-HPLC. We showed that
      the drug was more sensitive to metabolism with microsomes than with cytosol or S9
      fraction of rat liver cells. Incubation of C-1311 with microsomes revealed the
      presence of four metabolites. Their structures were identified as dealkylation
      product, M0, as well as a dimer-like molecule, M1. Furthermore, we speculate that
      the hydroxyl group was most likely substituted in metabolite M3. It is of note
      that a higher rate of transformation was observed for rat than for human
      microsomes. However, the differences in metabolite amounts were specific for each
      metabolite. The reactivity of C-1311 with rat microsomes overexpressing P450
      isoenzymes, of CYP3A and CYP4A families was higher than that with CYP1A and
      CYP2B. Moreover, the M1 metabolite was selectively formed with CYP3A, whereas M3
      with CYP4A. In conclusion, this study revealed that C-1311 varied in
      susceptibility to metabolic transformation in rat and human cells and showed
      selectivity in the metabolism with P450 isoenzymes. The obtained results could be
      useful for preparing the schedule of individual directed therapy with C-1311 in
      future patients.

PMID- 18084653
TI  - Effect of N-glycosylation inhibition on the synthesis and processing of classical
      swine fever virus glycoproteins.
AB  - Classical swine fever virus (CSFV) is often used as a surrogate model in
      molecular studies of the closely related hepatitis C virus. In this report we
      have examined the effect of the inhibition of glycosylation on the survival and
      maturation of CSFV. Viral glycoproteins (E(rns), E1, E2) form biologically active
      complexes - homo- and heterodimers, which are indispensable for viral life cycle.
      Those complexes are highly N-glycosylated. We studied the influence of N
      glycosylation on dimer formation using E(rns) and E2 glycoproteins produced in
      insect cells after infection with recombinant baculoviruses. The glycoproteins
      were efficiently synthesized in insect cells, had similar molecular masses and
      formed dimers like their natural counterparts. Surprisingly, the addition of
      tunicamycin (an antibiotic which blocks early steps of glycosylation) to insect
      cell culture blocked not only dimer formation but it also led to an almost
      complete disappearance of E2 even in monomeric form. Tunicamycin did not exert a
      similar effect on the synthesis and formation of E(rns) dimers; the dimers were
      still formed, which suggests that E(rns) glycan chains are not necessary for
      dimer formation. We have also found that very low doses of tunicamycin (much
      lower than those used for blocking N-glycosylation) drastically reduced CSFV
      spread in SK6 (swine kidney) cell culture and the virus yield. These facts
      indicate that N-glycosylation inhibitors structurally similar to tunicamycin may
      be potential therapeutics for the inhibition of the spread of CSFV and related
      viruses.

PMID- 18084655
TI  - Antibody-based cancer treatment with ultra-short range Auger electron-emitting
      radionuclides: dual receptor and DNA targeting strategies.
AB  - The long-heralded potential of targeted cancer treatment using monoclonal
      antibodies is finally being realized. Several antibodies are already used in the
      oncology clinic and many others are undergoing preclinical evaluation. In
      addition to the development of unconjugated antibodies, there is intense interest
      in the potential clinical use of antibodies as vehicles for targeting cytotoxic
      agents specifically to cancer cells. For example, radioimmunotherapy which
      involves the use of antibodies to deliver radionuclides to target cells is an
      approved treatment modality for cancer. Our laboratory is involved in developing
      technologies for radioimmunotherapy using a unique class of radionuclides, known
      as Auger electron emitters. A key feature of the Auger electrons emitted by these
      radionuclides is that they traverse very small ranges (molecular dimensions) in
      biological tissues. The emission of Auger electrons results in a gradient of
      energy deposition with the majority of the radiochemical damage occurring in the
      immediate vicinity (within a few cubic nanometers) of the decaying radionuclide.
      Therefore, realizing the full potential of Auger electron emitting isotopes in
      radioimmunotherapy requires more sophisticated approaches than directly
      radiolabeling anticancer antibodies. Strategies which involve targeting the
      radionuclide not only to cancer cells but also to the DNA of those cells are
      necessary. In this paper potential dual, receptor and DNA, targeting systems for
      radioimmunotherapy with Auger electron-emitting radionuclides are discussed.

PMID- 18084656
TI  - Gallium-67 citrate scintigraphy and marginal zone lymphoma of the mucosa
      associated lymphoid tissue. Ocular MALT.
AB  - We describe marginal zone lymphoma of the mucosa-associated lymphoid tissue
      (MALT) and especially MALT lymphoma occurring in the conjunctiva. Tumors of the
      conjunctiva and cornea are grouped into two major categories of congenital and
      acquired lesions. Lymphoid tumors of the conjunctiva are acquired tumors and can
      occur as an isolated lesion or can be a manifestation of systemic lymphoma.
      Primary lymphomas of the conjunctiva are extremely rare usually originate from
      extranodal marginal zone B-cell non-Hodgkin's lymphomas of MALT and occur among
      older adults with a mean age of 61 years. In the last decade it has been reported
      that MALT lymphomas may develop in various extraintestinal locations, sometimes
      even without the presence of a mucosa. Half of MALT lymphomas occur in the
      gastrointestinal tract. MALT lymphomas of the eye are rare and originate from the
      conjunctiva and the lacrimal glands. Studies evaluating the clinical impact of
      67Ga-C scintigraphy for MALT-type lymphomas imaging are rare, based on small
      numbers, heterogenous groups of patients. Clinical examination, excisional
      biopsy, histopathology and immunohistochemical studies, computerized tomography
      and magnetic resonance imaging are also used for the diagnosis of cunjunctival
      MALT disease. A case of ours gives reason for further discussion. Treatment and
      follow-up of MALT lymphoma is described.

PMID- 18084657
TI  - In-house preparation of iodine -131 metaiodo benzyl guanidine for scintigraphy of
      neuroendocrine tumors. Fourteen years experience in South India.
AB  - Iodine-131 metaiodobenzyl guanidine ((131)I-MIBG) is routinely used for imaging
      and treatment of neuroendocrine tumors (NET). As the commercially available
      radiopharmaceutical was very expensive, we developed an in-house method of
      labeling MIBG with (131)I in 1993. A total of 247 batches of (131)I-MIBG were
      prepared and used in our hospital between April 1993 and September 2006. We
      report our experience over these 14 years of preparation of this tracer in our
      hospital radiopharmacy, for the scintigraphy of NET. The technique of preparation
      is simple and the labeled product was found to be of acceptable quality. With the
      routine availability and cost effectiveness, the utilization of this
      radiopharmaceutical for scintigraphy increased remarkably in our institution.

PMID- 18084658
TI  - Zinc sulphate following the administration of iodine-131 on the regulation of
      thyroid function, in rats.
AB  - Hyperthyroidism in men is often treated with high doses of iodine-131 ((131)I),
      which may induce radiation side effects to patients and their environment. These
      therapeutic doses of (131)I could be decreased, if the (131)I uptake of the
      thyroid gland of the patients could be increased. Zinc sulphate has been
      considered to exercise a protective role by maintaining the cellular integrity of
      the thyroid under various pathological states. The aim of our study was to study
      in Wistar rats whether zinc sulphate can after treatment of the thyroid gland
      with (131)I: a) increase the uptake of (131)I in the thyroid and b) stabilize the
      function of the follicular cells. If such a stabilization finally exists in men
      we could have favorable results like fewer cases of hypothyroidism after (131)I
      treatment of hyperthyroidism. To carry out these investigations, rats were
      divided into four groups comprising of eight animals each. Group I animals served
      as normal controls. Group II animals received a dose of 3.7 MBq of (131)I. Group
      III animals were supplemented with zinc (227 mg/L of drinking water) and animals
      in Group IV were given (131)I together with zinc sulphate as above. Our results
      showed that in Group II, serum levels of tetra-iodo-thyronine (T(4)) and tri-iodo
      thyronine (T(3)) decreased significantly as a function of time following (131)I
      treatment. An increase in the levels of serum thyroid stimulating hormone (TSH)
      was noticed one week after (131)I treatment, becoming less pronounced with time.
      In Group II, thyroid uptake at 2h and at 24h was significantly decreased. In the
      same Group biological half life (T(biol)) of (131)I in the thyroid gland, was
      significantly elevated four weeks after the administration of (131)I and
      decreased eight weeks after. In Group IV animals, zinc sulfate after four weeks,
      induced normalization of elevated serum TSH levels and a further increase in the
      T(biol) of (131)I. After eight weeks in these animals, serum T(3) became normal
      and TSH remained at normal levels. Thyroid (131)I uptake at 2 and 24 h was
      increased as compared to Group II. Group III animals showed some increase in the
      levels of Na(+)K(+)ATPase and type 1,5'-deiodinase (5'-DI) as compared to normal
      rats of Group I. In conclusion, this study suggests the protective potential of
      zinc sulphate in the disturbed after (131)I treatment, thyroid function, thyroid
      hormones and TSH while the (131)I uptake was reduced. Thus, if this result is
      further confirmed, zinc sulphate may show to be a promising radioprotective agent
      for the thyroid gland.

PMID- 18084659
TI  - PET/CT findings in a multicentric form of Castleman's disease.
AB  - We report a case of a multicentric form of Castleman's disease (CD). A thoracic
      computerized tomography (CT) scan showed multiple mediastinal and bilateral
      axillary lymph nodes. Fluoro-18 fluoro deoxyglucose ((18)F-FDG) positron emission
      tomography-PET/CT scan demonstrated increased (18)F-FDG accumulation in multiple
      lymphatic regions and in bilateral pleural areas. The histopathological sampling
      of an excised left axillary lymph node revealed a multicentric form of CD, of an
      intermediate (mixed) cell type. The disease, its differential diagnosis and the
      diagnostic contribution of nuclear medicine imaging, are described.

PMID- 18084660
TI  - Unexpected dose to the daughter of a patient treated with iodine-131 for
      hyperthyroidism.
AB  - Patients treated with radioiodine for thyrotoxicosis and hyperthyroidism are a
      source of radiation exposure and represent a potential radiation hazard for the
      people in their environment. Doses to the relatives can be estimated from dose
      rates of the patient or measured with a proper dosimeter. Sensitive
      thermoluminescent dosimeters have been used to measure the doses absorbed by the
      family members of patients treated with iodine-131 ((131)I) for thyrotoxicosis.
      In the present case, a 12 year old daughter of a female patient, aged 41 years,
      treated with 592 MBq of (131)I, received a dose of 7.79 mSv during the first
      seven days. This value is well above the dose constraints proposed by the
      International Commission on Radiological Protection, i.e 1 mSv for children and
      fetuses and 3 mSv for carers. Obviously, the patient and her daughter didn't
      follow the given restrictions. That was unexpected for a 12 year old child who
      didn't need special care and was able to understand and follow certain
      instructions. It is the opinion of the authors that if there are children in the
      family of a hyperthyroid patient treated with (131)I, they should stay in another
      house for at least a week. If this is impossible for social reasons,
      hospitalization of the patient should be considered, although treatment of
      thyrotoxicosis is held in an out-patient basis.

PMID- 18084661
TI  - Jaw uptake of technetium-99 methylene diphosphonate in patients on
      biphosphonates: a word of caution.
AB  - Nitrogen-containing biphosphonates are a group of medications that are
      increasingly used in the management of Paget's disease, fibrous dysplasia,
      osteoporosis, multiple myeloma and metastatic prostate or breast cancer bone
      disease. On 2004 it was established that nitrogen-containing biphosphonates may
      induce jaw osteonecrosis and since then, a substantial number of publications has
      supported this finding. Jaw osteonecrosis may be asymptomatic, lasting for about
      a year or symptomatic, accompanied with mild or severe pain. Jaw osteonecrosis
      usually results in patients with poor dental hygiene, or subjected to invasive
      dental procedures. Its incidence increases with the length of nitrogen-containing
      biphosphonates treatment and appears to be higher for the Zometa(TM) users. It is
      important to early recognize this entity, since early intervention can make a
      significant difference to the outcome of this debilitating side effect. We here
      report three patients who had a positive technetium-99m methylene diphosphonate
      ((99m)Tc-MDP) bone scan. One of these patients also had osteomyelitis and was
      treated aggressively. The other two were treated in a more conservative manner.
      Detailed dental examination supported the scintigraphic findings. Biopsy was
      performed only in one patient and also offered specimens for antibiotic cultures.
      In discussion, jaw biopsy is a debatable procedure in the setting of jaw
      osteonecrosis and many consider that it should be avoided in most cases, except
      if it is necessary to establish the diagnosis and suggest antibiotic treatment by
      obtaining samples for bacterial cultures. Although axial tomography and magnetic
      resonance imaging are useful in defining the extent of the disease, 3-phase
      (99m)Tc-MDP bone scan is the most sensitive imaging modality pinpointing the
      disease at its early stages. In conclusion, a 3-phase (99m)Tc-MDP scan with
      anterior and lateral views of the skull is indicated in all symptomatic or
      asymptomatic patients, with a history of long-term nitrogen-containing
      biphosphonate treatment, since this may lead to an early detection of the
      disease.

PMID- 18084662
TI  - SPET brain scan with (99m)Tc-ECD and CT, MRI in traumatic brain injury with
      chronic symptoms.

PMID- 18084663
TI  - Two artifacts in the (131)I whole body post treatment scan in a thyroid cancer
      patient.

PMID- 18084664
TI  - Radionuclide renography: a seldom used test for the detection of vesicoenteric
      fistula.

PMID- 18084665
TI  - Lead exposure and nuclear medicine.

PMID- 18084666
TI  - A rare spontaneous cerebrospinal fluid rhinorrhea of long duration due to
      infection, detected by (99m)Tc-DTPA.

PMID- 18084667
TI  - [Nuclear Medicine in the diagnosis of lower gastrointestinal bleeding].
AB  - Lower gastrointestinal bleeding appears to be a frequent problem in the every day
      practice. The exact localisation of the bleeding site plays a major role in
      treatment planning. Nuclear Medicine imaging techniques allow the diagnosis of
      ectopic gastric mucosa-Meckel's diverticulum (MD) and the extravasation of red
      blood cells. Meckel's diverticulum is the most frequent congenital anomaly of the
      gastrointestinal system moreover bleeding seems to be the most important clinical
      symptom during childhood. Scintigraphy using technetium-99m pertechnetate
      ((99m)TcO(4)(-)) is the method of choice for the diagnosis of ectopic gastric
      mucosa in MD. The use of this test in children is of high diagnostic accuracy,
      with a sensitivity of 85%-95% and specificity of 90%-95%. In adults, lower
      gastrointestinal bleeding is commonly caused by tumors, colitis, dysplasias or
      polyps, while MD is rare. Scintigraphic demonstration of active lower
      gastrointestinal bleeding contributes to risk-stratification, to prognosis,
      appropriate timing for angiography and to planning of surgical intervention.
      (99m)Tc labelled erythrocytes and (99m)Tc sulphur colloid are commonly used
      radiopharmaceuticals each having its own indications and used for the diagnosis
      of active bleeding. Moreover delayed imaging is possible using (99m)Tc labelled
      erythrocytes, enabling the diagnosis of intermittent bleeding. Careful
      interpretation of the scintiscan images is essential to avoid numerous pitfalls.
      The indications for using the specific nuclear medicine technique as above, for
      the diagnosis of lower gastroinstestinal bleeding and the indications for using
      other methods besides those of nuclear medicine are described.

PMID- 18084668
TI  - [Single-photon emission computed tomography in the evaluation of brain tumors and
      the diagnosis of relapse vs radiation necrosis].
AB  - Morphologic characterization of brain tumors by magnetic resonance imaging and
      computed tomography is well established. However, functional metabolic imaging by
      single-photon emission tomography (SPET) and positron emission tomography are
      also increasingly important imaging tools for noninvasive assessment of brain
      tumors. Brain SPET is useful in the differentiation of tumor recurrence from
      radiation necrosis, in the non-invasive assessment of gliomas and meningiomas
      aggressiveness, in differentiating neoplastic from non neoplastic intracerebral
      haemorrhage, in monitoring therapy response and in the evaluation of other types
      of brain tumors. Our own experience is presented supporting the above.

PMID- 18084669
TI  - [Indium-111-DTPA-phenyl-pentetreotide somatostatin receptors' scintigraphy in the
      evaluation of patients with suspected gastro-entero-pancreatic tumors. Comparison
      with computerized tomography].
AB  - Gastro-entero-pancreatic tumors (GEP) contain, in their majority, somatostatin
      receptors. In-111-DTPA-phenyl-pentetreotide has been proved to have high affinity
      for somatostatin receptors subtypes 2, 3 and 5. The aim of the present study was
      to evaluate the utility of (111)In-DTPA-O somatostatin receptors' scintigraphy
      (SRS) in the diagnosis of suspected GEP. Thirty-five consecutive patients (17
      males and 18 females-mean age 57.9+/-7.6) with GEP as a possible diagnosis were
      enrolled in the study. The primary diagnosis was diarrheic syndrome susceptive of
      intestinal carcinoid tumor (24 patients), carcinoid of the rectum (2 patients),
      adenocarcinoma of the pancreas (2 patients), insulinoma (2 patients), gastrinoma
      (3 patients) and hepatocellular carcinoma (2 patients). All patients were
      submitted to computerized tomography (CT) of the thorax and the abdomen and
      pentetreotide SRS was performed 4 h (total body and SPET acquisition) and 24 h
      (planar views), post iv injection of 185 MBq of the radiolabeled compound.
      Results showed: Four of the patients were false positive diagnosed as having
      inflammatory intestinal disease and gallbladder dilatation. At the time of the
      evaluation, 14 of the remaining patients were free of disease, concerning
      secondary involvement. In these cases, CT and SRS studies matched each other,
      with no pathological lesions and no abnormal accumulation of the
      radiopharmaceutical respectively. Concerning pathological cases, only one SRS
      study in a patient with rectum carcinoid was normal, with liver lesions in the CT
      study. These lesions were considered as subtypes 2, 3 and 5 somatostatin
      receptors negative. SRS revealed three lesions more than CT. According to these
      results, sensitivity of SRS study was 93.8% and specificity 86.9%. The authors
      believe that molecular imaging of somatostatin receptors, is a sensitive method
      for the evaluation of patients with GEP tumors. However, in cases of intestinal
      disease, we should be aware of false positive results due to inflammatory
      processes and the presence of lymphocyte infiltration.

PMID- 18084670
TI  - DPP-4 Inhibitors and Combined Treatment in Type 2 Diabetes: Re-evaluation of
      Clinical Success and Safety.
AB  - The incretin system has proven to be a new source of glucose-lowering drugs.
      Glucon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)
      are the incretins which are degraded by dipeptidyl peptidase-4 (DPP-4). GLP-1 is
      the major relevant incretin in type 2 diabetes, GIP has little stimulatory
      capacity. Oral inhibitors of DPP-4 increase GLP-1 levels and this leads to lower
      glucose levels caused by increased insulin secretion and decreased glucagon
      levels. There are currently two oral drugs registered with the European Medicinal
      Evaluation Agency: sitagliptin and vidagliptin. Both compounds have shown similar
      effects to date. A main issue is to establish the value of this new class of
      drugs in the treatment of patients with type 2 diabetes. In this article, results
      from randomized studies on the efficacy of the new drugs are discussed: 1.
      comparison with placebo to establish long-term efficacy, 2. comparison with
      placebo when added to the regimen in patients failing on another oral glucose
      lowering drug and 3. comparison in a head-to-head trial with other conventional
      drugs. Also, the combination with insulin is a promising new avenue. Both
      efficacy and safety (regarding hypoglycemia, body weight changes and changes in
      lipid levels) are major components in the decision of the optimal pharmacological
      treatment, which is discussed in this article. Finally, the advantages,
      disadvantages and risks of the new anti-diabetic compounds are highlighted, which
      are applicable to other classes of diabetes drugs.

PMID- 18084672
TI  - Expression Analysis of cPLA2 Alpha Interacting TIP60 in Diabetic KKAy and Non
      Diabetic C57BL Wild-Type Mice: No Impact of Transient and Stable TIP60
      Overexpression on Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells.
AB  - In the present study we investigate the expression levels of cytosolic
      phospholipase A2 alpha (cPLA2alpha) interacting histone acetyl transferase
      proteins TIP60alpha and TIP60beta in non-diabetic C57BL wild-type mice and obese
      type 2 diabetic KKAy model mice. The aim was to test our hypothesis that TIP60
      plays a regulatory role in glucose-stimulated insulin secretion from pancreatic
      beta-cells. MATERIAL AND METHODS: Ten obese diabetic KKAy mice and ten non
      diabetic C57BL mice were fed a standard chow diet. After nine weeks, islet RNA
      was purified and used to measure TIP60 expression. We investigated the effect of
      TIP60alpha and TIP60beta on glucose-stimulated insulin secretion by transient and
      stable overexpression in the pancreatic mouse beta-cell line MIN6 and the rat
      beta-cell line INS-1E. RESULTS: We found that non-diabetic C57BL mice and
      diabetic KKAy mice have the same level of both the alpha and beta splice forms of
      TIP60. Furthermore, we demonstrated that transient and stable expression of TIP60
      in INS-1E cells affects neither glucose-stimulated insulin secretion, insulin
      output nor cell insulin content. Also susceptibility to developing gluco-toxicity
      was unaffected. CONCLUSION: TIP60 over-expression does not affect glucose
      stimulated insulin secretion, insulin content or abnormal beta-cell function
      during glucotoxicity.

PMID- 18084671
TI  - Adipose Tissue: A Metabolic Regulator. Potential Implications for the Metabolic
      Outcome of Subjects Born Small for Gestational Age (SGA).
AB  - Adipose tissue is involved in the regulation of glucose and lipid metabolism,
      energy balance, inflammation and immune response. Abdominal obesity plays a key
      role in the development of insulin resistance because of the high lipolytic rate
      of visceral adipose tissue and its secretion of adipocytokines. Low birth weight
      subjects are prone to central redistribution of adipose tissue and are at high
      risk of developing metabolic syndrome, type 2 diabetes and cardiovascular
      disease. Intrauterine adipogenesis may play a key role in the fetal origin of the
      pathogenesis of metabolic syndrome, type 2 diabetes and cardiovascular disease.
      Therefore, knowledge of the behavior of visceral adipose tissue-derived stem
      cells could provide a greater understanding of the metabolic risk related to
      intrauterine growth retardation, with potential clinical implications for the
      prevention of long-term metabolic alterations.

PMID- 18084673
TI  - Diabetic Cardiomyopathy in OVE26 Mice Shows Mitochondrial ROS Production and
      Divergence Between In Vivo and In Vitro Contractility.
AB  - Many diabetic patients suffer from a cardiomyopathy that cannot be explained
      solely by poor coronary perfusion. This cardiomyopathy may be due to either organ
      based damage like fibrosis, or to direct damage to cardiomyocytes. Mitochondrial
      derived reactive oxygen species (ROS) have been proposed to contribute to this
      cardiomyopathy. To address these questions, we used the OVE26 mouse model of
      severe type 1 diabetes to measure contractility in isolated cardiomyocytes by
      edge detection and in vivo with echocardiography. We also assessed the source of
      ROS generation using both a general and a mitochondrial specific indicator. When
      contractility was assayed in freshly isolated myocytes, contraction was much
      stronger in control myocytes. However, contractility of normal myocytes became
      weaker during 24 hours of in vitro culture. In contrast, contractility of
      diabetic OVE26 myocytes remains stable during culture. Echocardiography revealed
      normal or hyperdynamic function in OVE26 hearts under basal conditions but with a
      sharply reduced response to isoproterenol, a beta-adrenergic agonist. For ROS
      generation, we found that ROS production in diabetic myocytes was elevated after
      exposure to either high glucose or angiotensin II (AngII). Superoxide detection
      with the mitochondrial sensor MitoSOX Red confirmed that mitochondria are a major
      source of ROS generation in diabetic myocytes. These results show that
      contractile deficits in OVE26 diabetic hearts are due primarily to cardiomyocyte
      impairment and that ROS from mitochondria are a cause of that impairment.

PMID- 18084674
TI  - Diabetes and impaired glucose regulation in first-degree relatives of patients
      with type 2 diabetes in isfahan, iran: prevalence and risk factors.
AB  - OBJECTIVES: The aim of this study was to estimate the prevalence of diabetes,
      impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in first
      degree relatives (FDR) of people with type 2 diabetes mellitus. METHODS: A cross
      sectional study of FDR of type 2 diabetes patients was conducted between 2003 and
      2005. A total of 2,368 FDR of type 2 diabetes outpatients aged 30-60 years (614
      men and 1754 women) from Isfahan Endocrine and Metabolism Research Center (Iran)
      were examined. All subjects underwent a standard 75 g 2-h oral glucose tolerance
      test (OGTT). IGT, IFG and type 2 diabetes were diagnosed according to the
      criteria of the American Diabetes Association (ADA). The mean (SD) age of
      participants was 43.1 (6.9) years. RESULTS: The prevalence of type 2 diabetes,
      IGT and IFG were 10.3% (95% CI: 9.1-11.5), 19.5% (17.9-21.1) and 17.3% (15.8
      18.8) respectively. The prevalence rates were significantly higher than those
      reported for a control population of the same age (type 2 diabetes, 6.0% (95% CI:
      5.7-6.2) and IGT 9.6 (95% CI: 9.3-9.9)). IGT was more frequent among women (OR:
      0.66; 95% CI: 0.51-0.87), whereas diabetes (OR: 1.31; 95% CI: 0.96-1.78) and IFG
      (OR: 1.41; 95% CI: 1.10-1.80) were higher in men. Multivariate analysis revealed
      that age and obesity or abdominal obesity were significantly associated with
      diabetes, IGT and IFG. CONCLUSIONS: FDR of people with type 2 diabetes in Iran
      are at higher risk of IGT and type 2 diabetes than the population at large. Risk
      increases with age and obesity. These findings may be useful for the
      identification of persons at risk of developing type 2 diabetes and strongly
      support the regular screening of FDR of type 2 diabetes patients.

PMID- 18084675
TI  - Impact of metabolic syndrome risk factors in first-degree relatives of type 2
      diabetic patients.
AB  - OBJECTIVE: Family members of patients with an established diagnosis of type 2
      diabetes mellitus (T2DM) are theoretically at risk of having the metabolic
      syndrome (MetS). A sample of these family members was studied from a population
      in a small township in Argentina, which has a high prevalence of T2DM. METHODS:
      We examined the clinical and metabolic characteristics of 132 first-degree
      relatives of T2DM patients (FDR) and 112 age-matched controls. The subjects were
      categorized according to the International Diabetes Federation (IDF) and National
      Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria
      for MetS. RESULTS: The prevalence of MetS in the FDR group was 34.8 (IDF) and
      26.5% (NCEP-ATPIII) respectively, which was significantly different to the
      prevalence in controls (p < 0.025). According to IDF criteria, the most prevalent
      factors among FDR subjects with MetS were low HDL-cholesterol (87%) followed by
      hypertriglyceridemia (69.5%). In the MetS group, which ranged between 20-29 years
      old (36%), the major risk factor in women was a low HDL-cholesterol serum level.
      In the MetS group, which ranged between 30-39 years old (44.4%), the most
      important risk factor in men was hypertriglyceridemia. CONCLUSION: This study
      revealed that the prevalence of MetS is high in young FDR adults, who need urgent
      preventive treatment, including lifestyle changes. The risk of developing T2DM is
      five times higher in non-diabetic people with MetS than in those without the
      syndrome.

PMID- 18084676
TI  - Bromocriptine-induced hyperglycemia in nonobese diabetic mice: kinetics and
      mechanisms of action.
AB  - The effects of bromocriptine (10 mg/kg), known to inhibit prolactin secretion and
      lower autoimmune processes, were studied on glucose homeostasis in non-fasted non
      obese diabetic mice, a spontaneous model of type 1 diabetes. Hyperglycemia was
      observed 120 and 240 min after i.p. but not s.c. injection. Bromocriptine
      administration i.p. led to rapid and marked hyperglycemia characterized by sexual
      dimorphism with males having higher glycemia than females. Bromocriptine induced
      a rapid but transient decrease in insulinemia in males only and biphasic
      increases in glucagon levels and a sustained stimulatory effect on circulating
      corticosterone in both sexes. Bromocriptine-induced hyperglycemia involved D2
      dopaminergic receptors, as demonstrated by the inhibitory effect of the D2
      dopamine antagonist, metoclopramide (10 mg/kg). Simultaneous injection of
      bromocriptine and metoclopramide also blocked the rise in blood corticosterone.
      In conclusion, by inducing hyperglycemia, i.p. bromocriptine administration to
      prediabetic autoimmune mice may counteract its beneficial anti-immunostimulatory
      effects.

PMID- 18084677
TI  - Specific accumulation of 18F-deoxyglucose in three-dimensional long-term cultures
      of human and rodent brain tissue.
AB  - AIM: Organotypic slice cultures (OSC) of human brain specimens represent an
      intriguing experimental model for translational studies addressing, e.g., stem
      cell transplantation in neurodegenerative diseases or targeting invasion by
      malignant glioma ex vivo. However, long-term viability and phenomena of
      structural reorganization of human OSC remain to be further characterized. Here,
      we report the use of (18)F-deoxyglucose (FDG) for evaluating the viability of
      brain slice preparations obtained either from postnatal rats or human hippocampal
      specimens. METHODS: Anatomically well preserved human hippocampi obtained from
      epilepsy surgery and rat hippocampus slice cultures obtained from six day old
      Wistar rats were dissected into horizontal slices. The slices were incubated with
      FDG in phosphate buffered saline up to 1 h, either with or without
      supplementation of glucose at a concentration of 2.5 mg/ml. Radioactivity within
      the medium or slice cultures was measured using a gamma-counter. In addition,
      distribution of radioactivity was autoradiographically visualized and quantified
      as counts per mm(2). RESULTS: In rat hippocampal slices, FDG accumulated with 1
      300 000 +/- 68 000 counts/mm(2), whereas the incorporation of the radioactive
      label in human slices was in the order of 1 500 000 +/- 370 000 counts/mm(2). The
      elevation of glucose concentration within the medium led to a significant three
      fold decrease of FDG accumulation in rat slices and to a 2.4-fold decrease in
      human specimens. CONCLUSIONS: FDG accumulated in organotypic brain cultures of
      human or rodent origin. FDG is thus suited to investigate the viability of OSC.
      Furthermore, these preparations open new ways to study the factors governing
      cerebral FDG uptake in brain tissue ex vivo.

PMID- 18084678
TI  - Integrated FDG PET-CT imaging improves staging in malignant pleural mesothelioma.
AB  - AIM of this study was to investigate, how often TNM staging is changed in
      patients with malignant pleural mesothelioma (MPM) by the application of
      integrated PET-CT compared to computed tomography alone and how often these
      changes are clinically relevant. PATIENTS, METHODS: We studied 17 patients (68 +/
      6 years, 8 women) with MPM. Integrated PET-CT scan and histological confirmation
      were performed in all patients. RESULTS: Final histological diagnosis confirmed 9
      epithelial type, 2 sarcomatoid type and 6 biphasic type MPM. Mean standardized
      uptake value (SUV) was 5.9 +/- 1.9 in epithelial MPM and 15.1 +/- 10.2 in
      sarcomatoid MPM. CT and PET-CT revealed discordances in 8/17 (47%) patients in
      TNM classification with 4/8 (50%) being clinically relevant. PET-CT led to
      downstaging in 5 (29%) and upstaging in 3 (18%) patients. Mean survival time
      tended to be higher in the subgroup of patients with lower mean SUV. CONCLUSIONS:
      PET-CT seems to be a valuable tool in staging of MPM and leads to discordant
      findings in almost every second patient compared to CT alone. In many cases these
      differences are clinically relevant and have therapeutic consequences.

PMID- 18084679
TI  - Sentinel lymph node involvement and a high Breslow index are independent factors
      of risk for early relapse of melanoma.
AB  - AIM: The clinical relevance of sentinel lymph node (SLN) analysis was evaluated
      prospectively and compared with other known risk factors of relapse in early
      stage melanoma. METHODS: Surgery was guided by lymphoscintigraphy, blue dye and
      gamma probe detection. SLN were analysed by haematoxylin eosin (HE)
      histochemistry and multimarker immunohistochemistry (IHC). Disease free survival
      (DFS) was evaluated with Kaplan-Meier plots according to different parameters and
      Cox analyses of variance. RESULTS: From 210 patients a total of 381 SLN were
      excised. Lymphoscintigraphy identified all excised SLN with only 2 false positive
      lymphatic lakes. Fifty patients (24%) had tumour positive SLN. With a mean follow
      up of 31.3 months, 29 tumour recurrences were observed, 19 (38%) in 50 SLN
      positive and 10 (6%) in 160 SLN negative patients. Strong predictive factors for
      early relapse (p < 0.0005) were SLN positivity and a high Breslow index.
      CONCLUSION: SLN tumour positivity is an independent factor of high risk for early
      relapse with a higher power of discrimination than the Breslow index.

PMID- 18084680
TI  - Sentinel node SPECT-CT in breast cancer. Can we expect any additional and
      clinically relevant information?
AB  - The AIM of this study was to determine the additional value of SPECT/CT in
      sentinel node scintigraphy in breast cancer. Furthermore, it was our question to
      determine, whether the low-dose computed tomography component (LD-CT) can be used
      for axillary lymph node staging of clinically negative patients. PATIENTS,
      METHODS: 51 patients with invasive breast cancer <3 cm in diameter were included
      in our prospective investigation. SPECT/CT was performed on a dedicated scanner
      30 minutes after subareolar injection of (99m)Tc-Nanocoll. Axillary staging with
      CT(LD) was performed using standard CT-criteria. SLN were allocated to an
      axillary level using SPECT alone and SPECT/CT. Additionally, the number of SLN on
      CT(LD) corresponding to the scintigraphic hot node was notified for each patient
      and compared to the number of SLN found with the gamma probe. RESULTS: In 45/51
      evaluable patients SLN could be localised in level I in 43 patients and in level
      II in two patients (all positive) using SPECT-CT, whereas a clear allocation
      could not be obtained by SPECT alone. The number of SLN was discrepant between
      SPECT and CT(LD) in 13/45 patients. The number of SLN detected with the gamma
      probe (n = 68) not significantly differed from the number of SLN detected by
      CT(LD) (n = 65) but was significantly higher than with SPECT (n = 51). CT(LD)
      yielded a sensitivity of 35.7%, a specificity of 83.9%, a positive predictive
      value (PPT) of 50%, a negative predictive value (NPV) of 74.3% and a diagnostic
      accuracy of 68.9% for axillary staging with CT(LD). CONCLUSION: The additional
      information of SPECT/CT allows a more accurate characterization of the SN
      concerning size, depth and anatomical location. CT(LD) when performed during
      (99m)Tc-Nanocoll sentinel-SPECT/CT is not suitable for axillary staging in breast
      cancer patients with clinical negative axilla due to its low sensitivity and
      moderate specificity. Therefore, it does not influence the decision for SNB or
      ALND. The limited resolution of SPECT leads to an underestimation of the number
      of SLN compared to CT(LD) and the gamma probe.

PMID- 18084681
TI  - Multiparameter scoring system for the prognosis of differentiated thyroid cancer.
AB  - The AIM of the study was to develop a scoring system consisting of multiple
      parameters that are significant for prognosis of thyroid cancer. The score was
      designed to permit a risk stratification with all available information at any
      time of presentation. PATIENTS, METHODS: A score using 25 parameters was used for
      171 patients with differentiated thyroid cancer, who were included in follow up
      over a mean of 9 (+/- 5) years. The significance of each parameter as well as of
      a summation outcome score was determined. The result of this scoring system was
      compared to other scores reported in the literature applied to the same patients'
      group. Thirty-two out of the 171 patients presented with recurrence during follow
      up. RESULTS: The summation score was highly significant for prognosis of
      differentiated thyroid cancer. Out of 25 parameters, 18 showed a significant
      association with outcome also as individual parameters. In comparison to the
      scores commonly used, this new system showed the highest significance (p <
      0.0001, chi square 90, df 1) to estimate recurrence free survival. At a cutoff of
      -5.95 the sensitivity and specificity for the distinction between high and low
      risk patients were 87.5 and 77.0%, respectively. CONCLUSION: With our
      multiparameter scoring system a reliable prognosis with respect to recurrence
      free survival is possible in patients suffering from differentiated thyroid
      cancer. A summation score of all parameters gives the best results. Scoring is
      also possible, if several important parameters are missing.

PMID- 18084682
TI  - Visualisation of metastatic oesophageal and gastric cancer and prediction of
      clinical response to palliative chemotherapy using 18FDG PET.
AB  - AIM: This study assessed the value of (18)F-deoxyglucose positron emission
      tomography (FDG-PET) for visualisation and early metabolic response assessment in
      metastatic gastro-oesophageal cancer. PATIENTS, METHODS: Twenty-six patients who
      were treated for metastatic disease (20 adenocarcinomas, 6 squamous cell cancers)
      underwent FDG-PET before and two weeks after the onset of palliative chemotherapy
      with either oxaliplatin + 5-FU/LV or with docetaxel + capecitabine. PET results
      were validated according to clinical response based on RECIST criteria. RESULTS:
      Twenty-four tumours (92%) could be visualised by FDG-PET and were also assessable
      by a second PET scan at 2 weeks. The 2 tumours that were not detectable by PET
      were both gastric cancers belonging to the non-intestinal subtype according to
      Lauren. Median time to progression and overall survival were not significantly
      different for metabolic responders and non-responders (6.3 vs 5.3 months and 14.1
      vs 12.5 months, respectively). CONCLUSION: In this heterogeneous study
      population, FDG-PET had a limited accuracy in predicting clinical response.
      However, the metabolic response prediction was particularly good in the subgroup
      of patients with oesophageal squamous cell cancer. Therefore, FDG-PET and
      assessment of cancer therapy clearly merits further investigation in
      circumscribed patient populations with metastatic disease.

PMID- 18084683
TI  - Radiosynthesis and evaluation of [11C]BTA-1 and [11C]3'-Me-BTA-1 as potential
      radiotracers for in vivo imaging of beta-amyloid plaques.
AB  - AIM: To evaluate the in vitro and in vivo characteristics of [N-methyl-(11)C]2
      (4'-(methylaminophenyl)-benzothiazole ([(11)C]BTA-1) as well as [N-methyl-(11)C]2
      (3'-methyl-4'-(methylamino)phenyl)-benzothiazole ([(11)C]3'-Me-BTA-1) as
      diagnostic markers of amyloid-beta (Abeta) in Alzheimer's disease (AD). MATERIAL,
      METHODS: Brain uptake and clearance was determined in wild-type mice. Binding
      affinities (K(i)) of [(11)C]BTA-1 and [(11)C]3'-Me-BTA-1 for aggregated Abeta(1
      40) fibrils were assessed. Autoradiography was performed on brain sections of AD
      patients. To demonstrate binding specificity in vivo BTA-1 was injected i.p. in
      transgenic mice (Tg2576). Brain sections were analysed consecutively.
      Additionally, a [(11)C]BTA-1 PET study of an AD patient and a healthy control was
      performed. RESULTS: In mice brain uptake and clearance of [(11)C]BTA-1 is
      compatible with the half life of (11)C (2 min: 12.7 % ID/g; 30 min: 4.6% ID/g).
      In contrast clearance rate of [(11)C]3'-Me-BTA-1 is too slow (2 min 4% ID/g; 30
      min 12% ID/g) to achieve sufficient clearance of free and non specifically bound
      radioactivity. K(i) of [(11)C]BTA-1 is 11 nmol/l and that of [(11)C]3'-Me-BTA-1
      27 nmol/l. Both radioligands label Abeta selectively and specifically in AD
      patients and transgenic mice in vitro. The in vivo stained brain sections show a
      labelling of Abeta plaques. The AD patient has a higher prefrontal, parietal and
      striatal [(11)C]BTA-1 accumulation than the healthy control. Metabolite analysis
      revealed approximately 75% intact [(11)C]BTA-1 after 30min in plasma.[(11)C]BTA-1
      is favourable for in vivo imaging of Abeta due to its rapid brain entry,
      sufficient clearance and good binding affinity for Abeta. CONCLUSION: The ability
      to label Abeta plaques in vivo in human subjects supports the suitability of
      [(11)C]BTA-1 as a plaque imaging agent.

PMID- 18084684
TI  - Renogram and deconvolution parameters in diagnosis of renal artery stenosis.
      Variants of background subtraction and analysis techniques.
AB  - AIM: Multivariate statistical methods can be used for objective analysis. The
      emphasis is on analysing renal function parameters together, not one at a time.
      The aim is to identify curve parameters useful in making predictions in kidneys
      with and without renal artery stenosis (RAS). PATIENTS, METHODS: 68 patients with
      resistant hypertension were subjected to captopril renography with (99m)Tc-DTPA.
      Variants of background areas and background subtraction methods were employed. A
      correction was applied for loss of renal parenchyma. Parameters from time
      activity curves and retention curves from deconvolution were calculated. Renal
      angiography established the presence or absence of RAS. Logistic regression
      analysis, using age- and kidney size-adjusted models, was performed to assess the
      capability of renography and deconvolution to differentiate between kidneys with
      and without RAS. RESULTS: Discrimination between normal kidneys and RAS was
      achieved by deconvolution and by renography. Deconvolution was the method of
      first rank with a sensitivity of 87% and a specificity of 98%. For separation of
      RAS and kidneys with parenchymal insufficiency deconvolution was the method of
      first rank with a sensitivity of 80 % and specificity of 89 %, whereas renography
      produced poor results. CONCLUSION: The best performance with (99m)Tc-DTPA was
      based on normalised background subtraction using a rectangular area between the
      kidneys. Deconvolution produced the most favourable results in the separation of
      kidneys with and without RAS. For separation of RAS and kidneys with parenchymal
      insufficiency conventional renography produced poor results. Conceptually, the
      results of a logistic regression analysis of renal function parameters may raise
      possibilities in the field of computer-aided diagnosis.

PMID- 18084685
TI  - [FDG-PET/CT in oncology. German Guideline].
AB  - FDG-PET/CT examinations combine metabolic and morphologic imaging within an
      integrated procedure. Over the past decade PET/CT imaging has gained wide
      clinical acceptance in the field of oncology. This FDG-PET/CT guideline focuses
      on indications, data acquisition and processing as well as documentation of FDG
      PET/CT examinations in oncologic patients within a clinical and social context
      specific to Germany. Background information and definitions are followed by
      examples of clinical and research applications of FDG-PET/CT. Furthermore,
      protocols for CT scanning (low dose and contrast-enhanced CT) and PET emission
      imaging are discussed. Documentation and reporting of examinations are specified.
      Image interpretation criteria and sources of errors are discussed. Quality
      control for FDG and PET/CT-systems, qualification requirements of personnel as
      well as legal aspects are presented.

PMID- 18084686
TI  - Social anxiety disorder above and below the diagnostic threshold: prevalence,
      comorbidity and impairment in the general population.
AB  - BACKGROUND: There is a lack of data systematically describing subthreshold
      expressions of social anxiety disorder (SAD) with regard to prevalence,
      comorbidity, and impairment. METHODS: This analysis was based on data from the
      German Health Survey (GHS) and its Mental Health Supplement (GHS-MHS). Social
      anxiety disorder and its syndromes as well as other mental disorders were
      assessed with a standardized diagnostic interview (M-CIDI) in 4,174 adults.
      RESULTS: The 12-month prevalence rate for threshold SAD was 2.0%, subthreshold
      and symptomatic social anxiety (one DSM-IV criterion missing/two or more criteria
      missing) was found in 3.0 and 7.5% of the participants, respectively. As
      expected, threshold SAD was characterized by an elevated risk for comorbid
      disorders and associated with impairment in diverse areas of life. However, this
      was also true for the two subthreshold expressions of social anxiety, which were
      also significantly associated with higher comorbidity and greater impairment
      compared to the control group. CONCLUSIONS: Our results suggest that social
      anxiety below the diagnostic threshold is clearly associated with adverse
      outcomes. Prospective designs should examine the exact temporal and possible
      causal pathways of this burden in order to inform prevention and early
      intervention programs.

PMID- 18084687
TI  - Associations between type A behaviour pattern and psychological distress : 28
      years of follow-up of the Oslo Study 1972/1973.
AB  - OBJECTIVE: To investigate the relationships between type A behaviour pattern
      (TABP) and psychological distress measured in middle aged men participating in
      two surveys 28 years apart. DESIGN AND SUBJECTS: Men residing in Oslo and born in
      1923-1952 (all men aged 40-49 years and 7% of those aged 20-39 years--30,016
      altogether) were invited to a cardiovascular screening in 1972/1973--asking about
      risk factors, symptoms and diseases. All the 17,972 participants were also asked
      questions about TABP (two items) and psychological distress (one item). Of the
      original invited cohort, those who still lived in Oslo or its vicinity in 2000
      were invited to a new health examination carried through by similar procedures.
      Among other questions the participants answered ten items about psychological
      distress (Hopkins Symptoms Checklist: HSCL-10). Altogether 7,393 men participated
      in both surveys. RESULTS: In 1972/1973 almost 57% of those participating twice
      considered themselves as a person who stresses himself and chooses high speed and
      at the same time denied that they rather preferred a tranquil and quiet life--a
      combination of answers defined as type A behavior pattern. The corresponding TABP
      in 2000, when most of the men were retired, was 27%. A confirmatory factor
      analyses based on questions asked in 2000, verified that the HSCL/distress items
      reflected one underlying latent factor, and that this was a different factor than
      the one reflected in the two TABP items. The cross-sectional association between
      TABP and distress in 1972/1973 was highly significant (P < 0.001)--the odds ratio
      for psychological distress adjusted for background variables was 2.23 (95%
      confidence interval 1.98, 2.50). The corresponding association in 2000 showed a
      higher mean HSCL-10 score and a higher proportion with HSCL-score >or=1.85 in men
      with TABP compared with men without (P < 0.001 and P < 0.05, respectively), but
      the odds ratio in 2000 was lower than the result 28-years earlier. When those
      reporting psychological distress in 1972/1973 were excluded, TABP in 1972/1973
      predicted psychological distress (HSCL-10) in the follow-up survey when adjusted
      for background variables (P < 0.05) using structural equation modelling.
      CONCLUSION: Type A behaviour pattern and psychological distress reflect two
      different latent factors. TABP seems to be associated with psychological
      distress, both cross-sectionally and prospectively. This knowledge permits early
      detection of individuals who have a higher probability of experiencing
      psychological distress over a considerable period of time.

PMID- 18084688
TI  - Bicornuate uterine horns with complete cervical-vaginal agenesis and congenital
      vesicouterine fistula.
AB  - We present a case of bicornuate uterine horns with complete cervico-vaginal
      agenesis and associated congenital uterovaginal fistula. The patient presented
      with cyclical hematuria, amenorrhea, and abdominal lump. The vagina was blind
      ending. The cystoscopic examination during cyclical hematuria revealed bloody
      efflux through a small fistula on the posterior wall of the urinary bladder. The
      magnetic resonance imaging (MRI) showed bicornuate uterus and cervical agenesis.
      Hysterectomy and repair of the uterovesical fistula was done. The vagina was
      reconstructed using an amniotic mould. The report underlies the importance of MRI
      in diagnosing complexity of such rare anomalies. It also stresses for the need of
      hysterectomy if cervicovaginal agenesis is present.

PMID- 18084689
TI  - Protective effect of green tea polyphenols on bone loss in middle-aged female
      rats.
AB  - Recent studies have suggested that green tea polyphenols (GTP) are promising
      agents for preventing bone loss in women. Findings that GTP supplementation
      resulted in increased urinary GTP concentrations and bone mass via an increase of
      antioxidant capacity and/or a decrease of oxidative stress damage suggest a
      significant role of GTP in bone health of women. INTRODUCTION: Recent studies
      suggested that green tea polyphenols (GTP) are promising agents for preventing
      bone loss in women. However, the mechanism related to the possible protective
      role of GTP in bone loss is not well understood. METHODS: This study evaluated
      bioavailability, mechanisms, bone mass, and safety of GTP in preventing bone loss
      in middle-aged rats without (sham, SH) and with ovariectomy (OVX). A 16-week
      study of 2 (SH vs. OVX) x 3 (no GTP, 0.1% GTP, and 0.5% GTP in drinking water)
      factorial design using 14-month-old female rats (n = 10/group) was performed. An
      additional 10 rats in baseline group were euthanized at the beginning of study to
      provide baseline parameters. RESULTS: There was no difference in femur bone
      mineral density between baseline and the SH+0.5% GTP group. Ovariectomy resulted
      in lower values for liver glutathione peroxidase activity, serum estradiol, and
      bone mineral density. GTP supplementation resulted in increased urinary
      epigallocatechin and epicatechin concentrations, liver glutathione peroxidase
      activity and femur bone mineral density, decreased urinary 8-hydroxy-2'
      deoxyguanosine and urinary calcium levels, but no effect on serum estradiol and
      blood chemistry levels. CONCLUSION: We conclude that a bone-protective role of
      GTP may contribute to an increase of antioxidant capacity and/or a decrease of
      oxidative stress damage.

PMID- 18084690
TI  - Osteonectin/SPARC polymorphisms in Caucasian men with idiopathic osteoporosis.
AB  - Animal models suggest a role for osteonectin/SPARC in determination of bone mass.
      We found haplotypes consisting of three single nucleotide polymorphisms (SNPs) in
      the 3' untranslated region (UTR) of the osteonectin gene are associated with bone
      density in Caucasian men with idiopathic osteoporosis. INTRODUCTION: Osteonectin
      is a matricellular protein regulating matrix assembly, osteoblast
      differentiation, and survival. Animal studies indicate that osteonectin is
      essential for normal bone mass. The 3' UTR is a regulatory region controlling
      mRNA stability, trafficking, and translation, and we determined whether
      osteonectin 3' UTR haplotypes could be associated with bone mass and/or
      idiopathic osteoporosis. METHODS: Single strand conformation polymorphism and
      allele-specific PCR analysis were used to assess alleles at osteonectin cDNA
      bases 1046, 1599, and 1970, using genomic DNA from middle-aged Caucasian men with
      idiopathic, low turnover osteoporosis (n = 56) and matched controls (n = 59).
      Bone density was measured by DXA at spine, hip and radius. Allele and haplotype
      frequencies were analyzed by Chi square analysis and Fisher's exact test.
      RESULTS: Five common osteonectin 3' UTR haplotypes were identified. The frequency
      of one haplotype (1046C-1599C-1970T) was higher in controls compared with
      patients, and this haplotype was also associated with higher bone densities at
      multiple sites in patients. In contrast, a second haplotype (1046C-1599G-1970T)
      was associated with lower bone densities in patients at multiple sites.
      CONCLUSIONS: Osteonectin regulates skeletal remodeling and bone mass in animals,
      and haplotypes in the 3' UTR of this gene are associated with bone density in
      Caucasian men with idiopathic osteoporosis.

PMID- 18084691
TI  - Effect of dehydroepiandrosterone supplementation on bone mineral density, bone
      markers, and body composition in older adults: the DAWN trial.
AB  - We present results of a randomized, placebo-controlled trial to examine the
      effect of 50 mg daily oral DHEA supplementation for one year on bone mineral
      density (BMD), bone metabolism and body composition in 225 healthy adults aged 55
      to 85 years. INTRODUCTION: Dehydroepiandrosterone (DHEA) levels decline
      dramatically with age, concurrent with the onset of osteoporosis, suggesting a
      role for DHEA supplementation in preventing age-related bone loss. METHODS: We
      conducted a randomized, placebo-controlled trial to examine the effect of 50 mg
      daily oral DHEA supplementation for one year on bone mineral density (BMD), bone
      metabolism and body composition in 225 healthy adults aged 55 to 85 years.
      RESULTS: DHEA treatment increased serum DHEA and DHEA sulfate levels to
      concentrations seen in young adults. Testosterone, estradiol and insulin-like
      growth factor (IGF-1) levels increased in women (all p < 0.001), but not men,
      receiving DHEA. Serum C-terminal telopeptide of type-1 collagen levels decreased
      in women (p = 0.03), but not men, whereas bone-specific alkaline phosphatase
      levels were not significantly altered in either sex. After 12 months, there was a
      positive effect of DHEA on lumbar spine BMD in women (p = 0.03), but no effect
      was observed for hip, femoral neck or total body BMD, and no significant changes
      were observed at any site among men. Body composition was not affected by DHEA
      treatment in either sex. CONCLUSION: Among older healthy adults, daily
      administration of 50 mg of DHEA has a modest and selective beneficial effect on
      BMD and bone resorption in women, but provides no bone benefit for men.

PMID- 18084692
TI  - Secreted tartrate-resistant acid phosphatase 5b is a Marker of osteoclast number
      in human osteoclast cultures and the rat ovariectomy model.
AB  - PURPOSE: To study the effects of estrogen withdrawal on osteoclast number and
      osteoclast activity in the rat ovariectomy (OVX) model. METHODS: We first
      cultured human CD34+ osteoclast precursor cells on bovine bone slices, allowing
      them to differentiate into mature resorbing osteoclasts. Secreted tartrate
      resistant acid phosphatase 5b (TRACP 5b) and C-terminal cross-linked telopeptides
      of type I collagen (CTX) were determined from the culture medium. TRACP 5b
      correlated strongly with osteoclast number and CTX with osteoclast activity,
      facilitating their subsequent use in the rat OVX model. An 8 week OVX study was
      then performed including sham-operated rats receiving vehicle, OVX rats receiving
      vehicle, and OVX rats receiving 10 microg/kg/day 17 beta-estradiol (E2).
      Trabecular bone parameters were determined from the tibial metaphysis using
      peripheral quantitative computed tomography and histomorphometry. Osteoclast
      number was normalized with bone perimeter (N.Oc/B.Pm) and tissue area (N.Oc/T.Ar,
      indicating absolute number of osteoclasts). TRACP 5b and CTX were determined from
      fasting serum samples. RESULTS: Trabecular bone parameters indicated substantial
      bone loss after OVX that was prevented by E2. N.Oc/B.Pm increased after OVX,
      while N.Oc/T.Ar and TRACP 5b decreased, and TRACP 5b correlated strongly with
      N.Oc/T.Ar. However, CTX values increased after OVX, and the "resorption index"
      CTX/TRACP 5b showed more substantial changes than either CTX or TRACP 5b alone.
      CONCLUSION: These results show that TRACP 5b is a reliable marker of osteoclast
      number, and the index CTX/TRACP 5b is a useful parameter in rat OVX model. The
      high elevation of CTX/TRACP 5b values by OVX demonstrates that estrogen
      withdrawal generates high activity of osteoclasts in the rat OVX model.

PMID- 18084693
TI  - A depressive symptoms responsiveness model for differentiating fatigue from
      depression in the postpartum period.
AB  - Fatigue is both a symptom and a predictor of depression in women after
      childbirth. At the same time, postpartum fatigue is experienced by most non
      depressed women. Health care providers experientially know that not all women who
      experience postpartum fatigue will manifest depression. However, while
      researchers agree that fatigue and depression are distinct concepts, they have
      not yet identified a means for describing or measuring this distinctness. A new
      model proposing how fatigue may be differentiated from depression after
      childbirth is presented. The Depressive Symptoms Responsiveness Model proposes
      that depression-related postpartum fatigue may potentially be differentiated from
      non-depression-related postpartum fatigue on the basis of whether depressive
      symptoms abate when fatigue is relieved. The ability to differentiate between
      fatigue and depression in postpartum women has the potential to improve women's
      health through improvements in practice and resource utilization. Furthermore,
      differentiation may lead to a better understanding of the role of fatigue in
      postpartum depression.

PMID- 18084695
TI  - Update on the Japanese guidelines for the use of infliximab and etanercept in
      rheumatoid arthritis.
AB  - Application of biological agents targeting tumor necrosis factor-alpha (TNF
      alpha) caused a paradigm shift in the treatment of rheumatoid arthritis (RA). The
      introduction of infliximab in 2003 and etanercept in 2005 in Japan had a
      significant impact on both Japanese rheumatologists and RA patients, although
      serious adverse effects such as bacterial pneumonia, tuberculosis and
      Pneumocystis jiroveci pneumonia are significant concerns. Based on the data from
      post-marketing surveillance in Japan and accumulating evidence worldwide, the
      Internal Medicine Rheumatology Study Group of the Ministry of Health, Labor and
      Welfare (MHLW), Japan, has updated the guidelines for the use of anti-TNF-alpha
      agents for RA, which were subsequently approved by the Board of Japan College of
      Rheumatology (JCR). In the present revised guidelines, we combined the guidelines
      for use of each of infliximab and etanercept together with some modifications and
      precautions, paying special attention to serious adverse reactions. Although it
      is still controversial whether the use of TNF-alpha blocking agents per se
      increases the risk of infection or not, bacterial pneumonia, regardless of the
      pathogens, is the most frequent complications in RA. The risk factors associated
      with pneumonia identified in the post-marketing surveillance of infliximab in
      Japan are presented in this guideline. The diagnostic algorithm is also designed
      for early diagnosis and treatment of pulmonary lesions seen during the treatment
      of biological agents. Preventive measures and precautions against tuberculosis,
      another frequent and significant complication in Japan, are also described.
      Furthermore, risk factors for developing Pneumocystis pneumonia, which uniquely
      occurs at 30- to 50-fold frequency under TNF-alpha blockade therapy in Japan, are
      described here and its preventive measures are discussed. It is stressed that
      secondary-care rheumatologists should be better familiarized with the proper use
      of TNF-alpha blocking agents and be alert to any adverse events for a better
      management of RA patients.

PMID- 18084694
TI  - Splice-site mutations in the TRIC gene underlie autosomal recessive nonsyndromic
      hearing impairment in Pakistani families.
AB  - Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. To
      date, 67 autosomal recessive nonsyndromic hearing impairment (ARNSHI) loci have
      been mapped, and 24 genes have been identified. This report describes three large
      consanguineous ARNSHI Pakistani families, all of which display linkage to marker
      loci located in the genetic interval of DFNB49 locus on chromosome 5q13.
      Recently, Riazuddin et al. (Am J Hum Genet 2006; 79:1040-1051) reported that
      variants within the TRIC gene, which encodes tricellulin, are responsible for HI
      due to DFNB49. TRIC gene sequencing in these three families led to the
      identification of a novel mutation (IVS4+1G> A) in one family and the discovery
      of a previously described mutation (IVS4+2T> C) in two families. It is estimated
      that 1.06% (95% confidence interval 0.02-3.06%) of families with ARNSHI in
      Pakistan manifest HI due to mutations in the TRIC gene.

PMID- 18084696
TI  - Thymic stromal lymphopoietin secretion of synovial fibroblasts is positively and
      negatively regulated by Toll-like receptors/nuclear factor-kappaB pathway and
      interferon-gamma/dexamethasone.
AB  - Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine
      produced by epithelial cells and triggers dendritic cell-mediated Th2 type
      allergic inflammatory responses. This study investigated whether Toll-like
      receptor (TLR) ligands, lipopolysaccharide (LPS) and poly-IC affect TSLP
      production in synovial fibroblasts. Enzyme-linked immunosorbent assay showed that
      LPS and poly-IC upregulated TSLP production in synovial fibroblasts obtained from
      patients with rheumatoid arthritis (RA) and osteoarthritis (OA). In addition, we
      found that nuclear factor (NF)-kappaB inhibitor IMD-0354, dexamethasone, and
      interferon (IFN)-gamma inhibited the LPS- and poly-IC-induced TSLP production in
      RA and OA synovial fibroblasts. Thus, LPS and poly-IC can upregulate TSLP via a
      NF-kappaB pathway in synovial fibroblasts, which is downregulated by
      dexamethasone and interferon (IFN)-gamma. The current findings suggest that TSLP
      may be involved in the pathophysiology of inflammatory arthritis as well as
      allergic disease.

PMID- 18084698
TI  - The effect of disease activity on fat-free mass and resting energy expenditure in
      patients with rheumatoid arthritis versus noninflammatory arthropathies/soft
      tissue rheumatism.
AB  - Rheumatoid arthritis (RA) is a chronic joint disease of undetermined cause that
      is associated with significant disability. Low-grade fever, anemia, and weight
      loss are recognized extra-articular features associated with increased disease
      activity. Weight loss and cachexia are well-established features of RA. The
      mechanism behind weight loss in RA is not known and may be multifactorial.
      Reduced energy intake and hypermetabolism are the major two factors frequently
      implicated in the etiology of RA cachexia. One would expect the effect of the
      above two factors to be highest during increased disease activity and lowest
      during remission. The purpose of this study was: (a) to establish whether in RA
      patients changes in body composition mirror changes in disease activity, (b) to
      investigate the relation between the energy expenditures and weight loss, (c) to
      examine the dietary energy intake and its role in weight loss in RA patients, and
      (d) to investigate the relation between the cytokine interleukin (IL)-6 and other
      variables including resting energy expenditure (REE), body composition, and acute
      phase reactants. Fourteen patients with RA were age-, sex-, and race-matched with
      14 controls from patients with noninflammatory diseases/soft tissue rheumatism.
      The measurements included the following: disease activity assessment,
      anthropometric measurements, indirect calorimetry, and measurements of dietary
      intake. Blood was collected to measure the acute-phase reactants and IL-6 levels.
      We demonstrated that loss of fat-free mass (FFM) might accelerate during times of
      increased disease activity and is only partially restored during periods of
      reduced disease activity. This probably means that the extent of cachexia in RA
      patients is determined by the frequency and intensity of disease activity (flare)
      for a given disease duration. Hypermetabolism with increased REE was more evident
      during increased disease activity. Hypermetabolism in the face of increased
      energy intake continued to cause loss of the FFM. Interleukin-6 correlates with
      increased REE and erythrocyte sedimentation rate. There was no direct association
      between IL-6 level and low FFM. We conclude that loss of FFM is common in RA,
      cytokine production in RA is associated with altered energy metabolism, and
      preservation of FFM is important in maintaining good quality of life in patients
      with RA.

PMID- 18084697
TI  - Efficacy and safety of mizoribine for the treatment of Sjogren's syndrome: a
      multicenter open-label clinical trial.
AB  - This multicenter clinical trial was performed to evaluate the efficacy and safety
      of mizoribine for the treatment of Sjogren's syndrome. Fifty-nine patients with a
      definite diagnosis of Sjogren's syndrome received 150;Smg of mizoribine daily for
      16 weeks. The salivary secretion volume was determined at baseline, at weeks 8
      and 16 after the start of the study treatment by the Saxon test, and clinical
      manifestations were assessed by the investigator and the patients using a 10-cm
      visual analog scale (VAS). Adverse drug reactions were reported in 18 patients,
      of whom 6 patients had to discontinue the study due to such adverse reactions;
      however, no serious adverse drug reactions definitely related to the study drug
      were noted. The salivary secretion volume, the rate of change in salivary
      secretion, the patients' own assessments of dry mouth and dry eyes, the
      investigators' assessment of oral sicca symptoms, and the investigators' overall
      assessment improved following the treatment regimen with statistical significance
      at week 16 after the start of treatment in comparison to the baseline values.
      These results suggested that mizoribine may be effective in producing a
      subjective and objective amelioration of the glandular symptoms in patients with
      Sjogren's syndrome, without observing any serious adverse effects related to this
      drug.

PMID- 18084699
TI  - Risk factors for total knee arthroplasty in rheumatoid arthritis.
AB  - We conducted a study to assess the predictive factors for total knee arthroplasty
      (TKA) in a cohort of rheumatoid arthritis (RA) patients recruited and followed
      prospectively for 5 years. A linked registry study using information from a large
      observational cohort of RA patients followed at the Institute of Rheumatology,
      Tokyo Women's Medical University (IORRA) was done. Baseline routine clinical and
      laboratory assessments were recorded. The data were analyzed using the
      multivariate piecewise-linear Cox (PL-Cox) regression model; the model initially
      included variables such as gender, age, duration of the disease, visual analog
      scale (VAS) generated by physicians (VAS-physician), patient-reported VAS for
      pain (VAS-pain), VAS for general health (VAS-GH), disability level using the
      Japanese version of the Health Assessment Questionnaire (J-HAQ), C-reactive
      protein, erythrocyte sedimentation rate, rheumatoid factor (RF), and hemoglobin.
      Of the 3945 patients registered at baseline, 955 (24.2%) had pain or tenderness
      in their knee joints, and 114 (11.9%) had TKA surgery in one or both knee joints.
      On PL-Cox regression, the variables with positive coefficients were J-HAQ, VAS
      pain, VAS-physician, and RF positive; advanced age was associated with a reduced
      risk of TKA. The hazard ratios were: 0.920 for age >60 years; 2.64 for J-HAQ
      <1.5; 1.01 for J-HAQ >1.5; 1.47 for VAS-pain >6 (cm); 1.20 for VAS-physician >4
      (cm); and 2.08 for RF positive. The consistently predictive factors for TKA in RA
      were age, J-HAQ, VAS-pain, VAS-physician, and RF positive. Age greater than 60
      years was associated with a decreased risk of TKA, while J-HAQ from 0 to 1.5, VAS
      pain >6 (cm), and VAS-physician >4 (cm) were associated with an increased risk
      for TKA surgery. These results suggest that, when treating RA patients,
      physicians should pay particular attention to pain complaints, the patient's
      daily activity level, and the RF factor status.

PMID- 18084700
TI  - Enhanced effect of high-dose leukocytapheresis using a large filter in rheumatoid
      arthritis.
AB  - To evaluate the efficacy of high-dose leukocytapheresis (LCAP) using a large
      filter in patients with refractory rheumatoid arthritis (RA), we conducted a
      multicenter, nonrandomized, open-label clinical study. Thirty patients with
      highly active RA were treated with high-dose LCAP performed 3-5 sessions at 1
      week intervals using a CS-180S filter (CS-180S group); the treatment involves the
      removal of leukocytes from a higher blood volume per body weight (100;Sml/kg).
      The clinical response was evaluated at 4 and 8 weeks after a series of LCAP using
      the 28-joint disease activity score (DAS28). Similar data of 53 patients treated
      with conventional LCAP (60;Sml/kg) using a standard filter, CS-100, were compared
      as a control (CS-100 group). The CS-180S filter demonstrated a higher adsorption
      capacity for leukocytes, particularly lymphocytes. The CS-180S group exhibited
      significant improvements in each item of DAS28 after treatment although the CS
      100 group did not demonstrate such improvements in the CRP level and the ESR.
      Compared to the CS-100 group, the patients of the CS-180S group exhibited a
      tendency toward improvement with respect to the CRP level and ESR (P = 0.057 and
      0.041, respectively). According to the EULAR improvement criteria based on DAS28,
      60% and 45% of the patients from CS-180S and CS-100 groups achieved moderate or
      more responses, respectively, at 4 weeks after treatment. These results suggest
      that compared to conventional LCAP, high-dose LCAP may enhance the suppression of
      RA disease activity.

PMID- 18084701
TI  - Primary biliary cirrhosis in female subjects with sicca-associated antibodies.
AB  - The aim of this study is to clarify the time course of primary biliary cirrhosis
      (PBC) in subjects possessing anticentromere antibodies (ACA), anti-Ro, and/or
      anti-La antibodies, and who used alkaline phosphatase (ALP) as a serological
      marker for PBC. Female subjects (n = 165), who had at least one of ACA, anti-Ro,
      and/or anti-La, were enrolled in this study. Groups A (ACA alone, n = 44), B
      (anti-Ro alone, n = 54), E (anti-Ro and anti-La, n = 52), and DFG (ACA with anti
      Ro and/or anti-La, n = 14) were analyzed. Healthy females (n = 65) were used as a
      control. The frequencies of the PBC in groups A (13.6%) and DFG (14.3%) were
      higher than those in groups B (1.9%) and E (0.0%). The ALP levels increased with
      age in groups A and DFG and slightly increased with age in groups B and C, and
      the control group. After correcting for age by analysis of covariance, a
      comparison of ALP levels among the groups not having anti-M(2) was as follows:
      group A falling dots group DFG > group B falling dots group E falling dots the
      control group. The subjects with ACA might thus have PBC more frequently than
      either those with anti-Ro and/or anti-La, or the control subjects.

PMID- 18084702
TI  - Infectious mononucleosis-like syndrome induced by salazosulfapyridine in a
      patient with rheumatoid arthritis.
AB  - We describe a 43-year-old woman with rheumatoid arthritis (RA), who developed
      severe infectious mononucleosis (IM)-like syndrome during treatment with
      salazosulfapyridine (SASP). She presented with fever, skin rash, lymphadenopathy,
      and hepatosplenomegaly. Laboratory tests revealed a marked increase of atypical
      lymphocytes in the peripheral blood and biphasic hepatic dysfunction. IM-like
      syndrome can be caused by various drugs, including SASP, and the concept of drug
      induced hypersensitivity syndrome has been proposed recently. IM-like syndrome
      due to SASP has been reported in patients taking higher dosages for the treatment
      of inflammatory bowel disease, but has not been reported earlier in patients with
      RA. The results of the drug-induced lymphocyte stimulation test tests suggested
      that 5-aminosalicylic acid was a possible causative metabolite. This severe type
      of drug-induced hypersensitivity reaction mimicking IM due to SASP should be
      granted wider awareness in the field of rheumatology, because the drug is widely
      used for the treatment of RA.

PMID- 18084703
TI  - A case of Muckle-Wells syndrome caused by a novel H312P mutation in NALP3
      (cryopyrin).
AB  - Here, we report a case of Muckle-Wells syndrome (MWS) caused by a novel mutation
      in the CIAS1/NALP3 gene. A 23-year-old woman had recurrent self-limited
      inflammatory episodes from childhood, with headache, abdominal pain, arthritis,
      and urticarial rash, associated with profound sensorineural hearing loss. The
      diagnosis was established on the basis of a typical clinical picture together
      with a missense mutation, which replaced an amino acid adjacent to one in an
      earlier reported case of MWS resembling this one.

PMID- 18084704
TI  - Early rheumatoid arthritis in a patient with Sjogren's syndrome and pulmonary
      nodular amyloidosis: clinical implication of early limited use of infliximab.
AB  - Infliximab, an anti-tumor necrosis factor alpha antibody, is among the most
      effective therapies for rheumatoid arthritis (RA). In this study, we report a
      patient with early RA of 6 months who has Sjogren's syndrome and pulmonary
      nodular lesions concomitantly. The patient did not respond to methotrexate (MTX,
      6;Smg per week) for 3 months. When introduction of infliximab therapy is
      considered, we need to exclude the possibility of pulmonary granulomatous
      infection and malignancy. With the use of computed tomography-guided percutaneous
      needle biopsy and subsequent histological examinations, this case was rapidly and
      confidently diagnosed as localized pulmonary nodular amyloidosis. Immunochemical
      staining showed light chain type nodular amyloidosis by a deposition of
      immunoglobulin kappa light chains, which is a rare condition in a patient with
      Sjogren's syndrome. We started combination therapy of infliximab (200;Smg per
      infusion) and MTX (6;Smg per week). Because of severe systemic eruption, this
      therapy was stopped halfway through the third infusion of infliximab, and MTX
      monotherapy was continued. Despite the withdrawal of infliximab therapy, the C
      reactive protein values were decreased to an undetectable level at week 14, and
      the disease activity score for 28 joints was 3.1 at week 22. Clinical remission
      has been maintained more than 14 months with MTX alone. Infliximab has been used
      only for patients with recalcitrant RA, because the cost of its lifelong use
      would be an economic burden in most cases. An optimal and affordable strategy for
      the treatment of early RA should be developed. Our findings may support the idea
      that the combination therapy of infliximab and MTX for early RA alters the course
      of the disease.

PMID- 18084705
TI  - Severe bone defects and reduced mineralization caused by massive metallosis after
      total knee arthroplasty: histopathologic and bone morphometric findings.
AB  - We encountered a patient who developed metallosis after total knee arthroplasty
      (TKA), resulting in loosening of the implant, bone resorption, reduced bone
      formation, and fracture. The implant was replaced with a NexGen modular revision
      TKA system after autologous bone and hydroxyapatite granule grafting.
      Histopathologic examination showed accumulation of metallic debris and tartrate
      resistant acid phosphatase-positive cells around the trabecular and cortical
      bone. Examination of hard tissue specimens showed a reduced bone volume
      (determined by bone histomorphometry) and an increase of all osteoid parameters,
      indicating disturbance of mineralization in addition to increased bone
      resorption.

PMID- 18084706
TI  - Gynecomastia associated with low-dose methotrexate therapy for rheumatoid
      arthritis.
AB  - A 68-year-old man with a 3-year history of rheumatoid arthritis (RA) developed
      gynecomastia 3 months after beginning oral low-dose methotrexate (MTX) therapy.
      Four months after MTX therapy was discontinued, the gynecomastia symptoms
      improved. Only eight cases of gynecomastia resulting from low-dose MTX
      administration have been reported worldwide, and no cases have previously been
      reported in Japan. Although it occurs infrequently, gynecomastia resulting from
      low-dose MTX therapy should be considered in male patients with RA.

PMID- 18084707
TI  - A case of proteinase 3-antineutrophil cytoplasmic antibody-positive Sjogren's
      syndrome complicated with interstitial nephritis.
AB  - A 65-year-old woman who had fever was admitted. Laboratory data showed renal
      tubular dysfunction, elevated C-reactive protein, soluble interleukin-2 receptor
      (sIL-2R), and IgG. Her blood showed proteinase 3-antineutrophil cytoplasmic
      antibody (PR3-ANCA) as well as antinuclear antibody and anti-Ro/SS-A antibody.
      Salivary gland and renal biopsy showed inflammatory infiltration of lymphocytes.
      A diagnosis of Sjogren's syndrome (SS) and interstitial nephritis was made.
      beta(2)-microglobulin, sIL-2R, IgG, and PR3-ANCA were decreased in response to
      medium-dose oral prednisolone. Antineutrophil cytoplasmic antibody could be a new
      marker for extraglandular features of SS. It would be beneficial for SS patients
      who have positive ANCA to investigate extraglandular lesions such as interstitial
      nephritis.

PMID- 18084708
TI  - Left ventricular aneurysms developed in a patient with systemic sclerosis.
AB  - A 60-year-old woman with systemic sclerosis, lung fibrosis, and primary biliary
      cirrhosis was admitted to our hospital because of heart failure. Ventricular
      aneurysms were found in the apex and the posterior wall of the left ventricle by
      angiocardiography; however, there was no sign of coronary artery stenosis. A
      myocardial biopsy specimen revealed diffuse focal myocardial fibrosis. In this
      case, the patient with systemic sclerosis developed a rare complication of
      ventricular aneurysms without coronary disease.

PMID- 18084709
TI  - A case of Wegener's granulomatosis associated with progressive dysphagia owing to
      esophageal involvement.
AB  - A 52-year-old woman was admitted to our hospital with progressive dysphagia.
      Upper gastrointestinal endoscopy revealed esophageal stenosis and computed
      tomographic scan revealed symmetrical wall thickness of the thoracic esophagus.
      Biopsies findings from a lesion were unremarkable. However, a definitive
      diagnosis of Wegener's granulomatosis was based on positive anti-neutrophil
      cytoplasmic antibodies directed against proteinase 3 and otorhinolaryngological
      manifestations. Esophageal complications are rarely reported in Wegener's
      granulomatosis; however, clinicians should be aware of the possibility of
      esophageal involvement.

PMID- 18084710
TI  - Switching the therapy from etanercept to infliximab in a child with rheumatoid
      factor positive polyarticular juvenile idiopathic arthritis.
AB  - Tumor necrosis factor alpha (TNFalpha)-blocking agents have been used
      increasingly in the treatment of severe refractory juvenile idiopathic arthritis
      (JIA). However, some patients have been forced to discontinue these agents
      because of the lack of efficacy or adverse events. In these situations, cases of
      switching from one TNF-blocking agent to another are reported in rheumatoid
      arthritis, but there are few cases in JIA. This report documents the case of a
      patient with JIA who improved following a switch from etanercept to infliximab.

PMID- 18084711
TI  - Trochanteric bursa effusion heralding relapse of lung adenocarcinoma.

PMID- 18084712
TI  - Anti-tumor necrosis factor therapy does not diminish the immune response to
      influenza vaccine in Japanese patients with rheumatoid arthritis.

PMID- 18084713
TI  - A comprehensive, time-resolved SANS investigation of temperature-change-induced
      sponge-to-lamellar and lamellar-to-sponge phase transformations in comparison
      with 2H -NMR results.
AB  - Time-resolved small-angle neutron scattering (TR-SANS) was employed to observe
      temperature-induced phase transitions from the sponge (L (3) to the lamellar ( L
      (alpha) phase, and vice versa, in the water-oil (n -decane)-non-ionic surfactant
      ( C(12)E(5) system using both bulk and film contrast. Samples of different
      bilayer volume fractions phi and solvent viscosities eta were investigated
      applying various amplitudes of temperature jump DeltaT . The findings of a
      previous (2)H -NMR study could be confirmed, where the lamellar phase formation
      was determined to occur through a nucleation and growth process, while it was
      concluded that the L (3) -phase develops in a mechanistically different and more
      rapid manner involving uncorrelated passage formation. Likewise, the kinetic
      trends of the nucleation and growth transition (decreased transition time with
      increase of phi and DeltaT were witnessed once again. Additionally, NMR and SANS
      data that demonstrate a strong dependency of that process on solvent viscosity
      eta are presented. Contrariwise, it is made evident via both SANS and NMR results
      that the L (alpha) -to-L (3) transition time is independent (within experimental
      sensitivity) of the varied parameters (phi , DeltaT , eta . Unusual scattering
      evolution in one experiment, originating from a highly ordered lamellar phase,
      intriguingly hints that a major rate determining factor is the disruption of long
      range order. Furthermore, the bulk contrast investigations give insight into
      structure peak shifts/development during the transitions, while the film contrast
      experiments prove the bilayer thickness to be constant throughout the phase
      transitions and show that there is no evidence for a change in the short-range
      order of the bilayer structure. The latter was considered possible, due to the
      different topology of the L (3) and L (alpha) phases. Lastly, an unexpected yet
      consistent appearance of anisotropic scattering is detected in the L (3) -to- L
      (alpha) transitions.

PMID- 18084714
TI  - Clearance of chronic HCV infection during acute delta hepatitis.
AB  - The course of chronic hepatitis C in acute HDV/HBV superinfection is unknown.
      Here, we report a patient with chronic hepatitis C who cleared HCV during acute
      self-limited hepatitis B/D superinfection. Recovery from HCV was associated with
      the appearance of a strong and multispecific HDV-specific memory CD4+ and CD8+ T
      cell response - but only weak HCV-specific CD4+ T cell responses. These data
      suggest that HCV can be cleared by bystander mechanisms during acute infections
      with other pathogens which may be considered in the development of
      immunotherapies for hepatitis C.

PMID- 18084715
TI  - Nitrogen and oxygen molecules in meningitis-associated labyrinthitis and hearing
      impairment.
AB  - Pneumococcal meningitis remains a serious disease with a case fatality rate of
      15%-25%. Furthermore, long-term residues affect up to 50% of survivors. One of
      the most frequent sequelae is sensorineural hearing loss, which occurs in 26% of
      survivors of pneumococcal meningitis. Unfortunately, sufficient treatment
      regimens are still missing. New insights into the pathology and pathophysiology
      of meningitis-associated hearing loss have come from animal models of bacterial
      meningitis. Most likely, bacteria reach the cochlea through the cochlear
      aquaeduct. Once arrived in the perilymphatic spaces, they induce a severe
      suppurative labyrinthitis. The blood-labyrinth barrier breaks, hair cells are
      damaged, and neurons in the spiral ganglion undergo cell death, leading to
      meningitis-associated hearing loss. Reactive oxygen and nitrogen species, in
      particular peroxynitrite, seem to be among the crucial mediators of cochlear
      damage and hearing loss during meningitis. In our rat model of pneumococcal
      meningitis, adjunctive therapy with the antioxidants and peroxynitrite scavengers
      Mn(III)tetrakis(4-bencoic acid)-porphyrin (MnTBAP) and N-Acetyl-L-Cystein (NAC)
      significantly attenuated acute and long-term hearing loss. In several other
      animal studies of pneumococcal meningitis, adjunctive antioxidant therapy also
      protected infected animals from intracranial complications. Therefore, the use of
      antioxidants seems to be a promising future treatment option in pneumococcal
      meningitis.

PMID- 18084716
TI  - Disseminated tuberculosis following total knee arthroplasty in an HIV patient.
AB  - Skeletal tuberculosis is now uncommon in developed countries. In
      immunocompromised patients--particularly in the HIV-infected--who present with
      subacute or chronic joint pain refractory to conventional treatment,
      osteoarticular tuberculosis should still be included in the differential
      diagnosis. We report on a lethal case of disseminated tuberculosis in an HIV
      infected subject. Dissemination may have resulted from the implantation of an
      articular prosthesis in a knee joint with unsuspected osteoarticular
      tuberculosis. The diagnosis was established months later when the patient
      presented with far-advanced tuberculous meningitis, miliary tuberculosis of the
      lungs, femoral osteomyelitis and extended cold abscesses along the femoral shaft.
      Failure to respond to a conventional four-drug regimen is explained by the
      resistance pattern of his multi-drug resistant strain of Mycobacterium
      tuberculosis, which was only reported after the patient's death. This case
      illustrates the diagnostic challenges of osteoarticular tuberculosis and the
      consequences of a diagnostic delay in an HIV-infected individual.

PMID- 18084717
TI  - Septic arthritis due to Absidia corymbifera in a patient with HIV-1 infection.
AB  - We report the first case described of septic arthritis caused by Absidia
      corymbifera in the setting of cellular immune deficiency associated with HIV-1
      infection. Isolation of this organism from sterile fluids as synovial fluid
      should be regarded as pathogenic.

PMID- 18084718
TI  - Retinopathy in Rickettsia conorii infection: case report in an immunocompetent
      host.
AB  - Mediterranean spotted fever (MSF) is an acute febrile, zoonotic disease caused by
      Rickettsia conorii. MSF is considered a relatively benign disease, but severe
      complications occur occasionally. However, reports of ocular involvement are few.
      We describe a case of retinal manifestation in a patient with R. conorii
      infection.

PMID- 18084719
TI  - Epidemiological characteristics of fatal Candida krusei fungemia in
      immunocompromised febrile neutropenic children.

PMID- 18084720
TI  - Descriptive epidemiology of primary spinal cord tumors.
AB  - OBJECT: There is little population-based data available on primary spinal cord
      tumors. Many of the existing statistics are not current or were obtained from
      surgical series. Historically, population-based data were collected only for
      malignant tumors, and only recently have data begun to be collected on non
      malignant tumors. The objective of this study was to estimate the incidence of
      both non-malignant and malignant primary spinal cord tumors and to estimate the
      survival rates for primary malignant spinal cord tumors. METHODS: Incidence of
      spinal cord tumors was estimated from cases diagnosed between 1998 and 2002 in 16
      CBTRUS collaborating state cancer registries. Age-adjusted rates were generated
      using SAS (8.2) and standardized to the 2000 US standard population. SEER*Stat
      6.1.4 software was used to estimate relative survival for malignant spinal cord
      tumors for cases diagnosed between 1975 and 2002 in nine SEER regions.
      CONCLUSIONS: Of the spinal cord tumors identified (CBTRUS; n = 3,226), 69% were
      non-malignant. The most common histologic types were meningiomas (29%), nerve
      sheath tumors (24%), and ependymomas (23%). The overall incidence of spinal cord
      tumors was 0.74 per 100,000 person-years, with an incidence of 0.77/100,000 in
      females and 0.70/100,000 in males. The incidence rate was lowest in children
      (0.26) and peaked in the 75-84 year age group (1.80). Rates were higher in non
      Hispanic whites (0.79) than in Hispanics (0.61) or non-Hispanic blacks (0.45).
      The 1-, 5-, and 10-year survival rates following diagnosis of a primary malignant
      spinal cord tumor were 85%, 71%, and 64%, respectively (SEER; n = 1,220).

PMID- 18084721
TI  - Anti-glioblastoma effect of a recombinant bispecific cytotoxin cotargeting human
      IL-13 and EGF receptors in a mouse xenograft model.
AB  - To improve activity of a recombinant IL-13 cytotoxin (CT) comprised of IL-13
      spliced to truncated diphtheria toxin (DT(390)), epidermal growth factor (EGF)
      was added to the same single chain protein. This new recombinant bispecific CT,
      called DTEGF13, enhanced the killing potency against the human glioblastoma
      lines, U87MG (0.015 nM) and U118MG (0.02 nM). A similar enhancement was observed
      against the lung carcinoma cell line, Calu-3 (0.0018 nM). Enhanced activity could
      not be explained by an increased number of cytokines available for binding since
      a combination of monospecific DTEGF and DTIL13 did not cause the same enhanced
      activity. Enhanced activity was dependent on the presence of both cytokines on
      the same single chain molecule and killing was receptor specific since target
      receptor negative leukemia cells were unaffected by the highly selective DTEGF13
      and cytotoxicity could be blocked with anti-EGFR and anti-IL-13 antibodies. In a
      xenograft flank tumor model, intratumoral injection of DTEGF13, but not
      monospecific DTEGF or DTIL13, significantly inhibited the growth of established
      U87 tumors in nude mice (P < 0.04). In this model, the human EGF and IL-13
      components of DTEGF13 are reactive with mouse EGFR and IL-13R, respectively.
      These studies show that a new co-targeting agent that simultaneously recognizes
      EGFR and IL-13R is more effective than its monospecific counterparts and that
      DTEGF13 has therapeutic advantages for glioblastoma.

PMID- 18084722
TI  - Role of ACE/AT2R complex in the control of mesenteric resistance artery
      contraction induced by ACE/AT1R complex activation in response to Ang I.
AB  - OBJECTIVES: In this study, we will determine the function of the interaction
      between AT2R and ACE, and AT1R and ACE in the control of mesenteric resistance
      artery (MRA) tone from normotensive (NT) and Angiotensin II (AII)-dependent
      hypertensive (HT) mice. METHODS-RESULTS: Hypertension was induced by infusion of
      Ang-II (200 ng/kg/day) for 3 weeks. Freshly MRA (100-120 microm) were isolated
      from HT and NT mice and mounted in an arteriograph. Dose-response of Ang-I
      induced a similar contraction of MRA from NT and HT mice, which was increased
      after endothelium removal. AT2R antagonist (PD123319, 1 microM) significantly
      increased Ang-I-induced contraction of MRA from NT but not from HT mice. In
      addition, PD123319 significantly increased in vivo blood pressure in response to
      Ang-I. Luminal incubation with ACE-antibody (50 ng/ml) to block only endothelial
      ACE function significantly enhanced Ang-I-induced contraction of MRA from NT
      mice. ACE inhibitor (captopril, 10 microM) completely blocked Ang-I-induced
      contraction of MRA from both animals and prevented the increased blood pressure.
      Freshly isolated MRA subjected to immunoprecipitation, Western blot analysis and
      RT-PCR revealed AT1R/ACE and AT2R/ACE complexes formation, and similar AT1R,
      AT2R, and ACE expression level in both groups. CONCLUSION: The present findings
      show the existence of ACE/AT2R and ACE/AT1R complexes on endothelial cells and
      VSMC, respectively. ACE/AT2R complex plays a modulator effect on ACE/AT1R-SMC
      induced contraction of MRA, which is altered in hypertension.

PMID- 18084724
TI  - Trends in penetrating keratoplasty in the United States 1980-2005.
AB  - In this review, we analyze the trends in corneal transplantation over the past 25
      years in the United States. The most dramatic change was the progressive sharp
      increase in the number of corneal transplants performed during the 1980s,
      corresponding with the rise of pseudophakic bullous keratopathy (PBK) as the
      leading indication for keratoplasty. More recently, there has been a steady
      annual decline in total keratoplasties for more than a decade, corresponding with
      a decline in the cases performed for PBK, which still accounts for the highest
      percentage of cases done. Regrafts have been an increasingly important indication
      for keratoplasty, as older grafts fail. Keratoconus, Fuchs dystrophy, and other
      inherited diseases have remained consistent indications for keratoplasty during
      the last quarter century.

PMID- 18084723
TI  - ZNF418, a novel human KRAB/C2H2 zinc finger protein, suppresses MAPK signaling
      pathway.
AB  - Cardiac differentiation involves a cascade of coordinated gene expression that
      regulates cell proliferation and matrix protein formation in a defined temporal
      spatial manner. Zinc finger-containing transcription factors have been implicated
      as critical regulators of multiple cardiac-expressed genes, and are thought to be
      important for human heart development and diseases. Here, we have identified and
      characterized a novel zinc finger gene named ZNF418 from a human embryo heart
      cDNA library. The gene spans 13.5 kb on chromosome 19q13.43 encompassing six
      exons, and transcribes a 3.7-kb mRNA that encodes a protein with 676 amino acid
      residues. The predicted protein contains a KRAB-A box and 17 tandem C2H2 type
      zinc finger motifs. Northern blot analysis indicates that ZNF418 is expressed in
      multiple fetal and adult tissues, but is expressed at higher levels in the heart.
      Reporter gene assays show that ZNF418 is a transcriptional repressor, and the
      KRAB motif of ZNF418 represents the basal repressive domain. Overexpression of
      ZNF418 in COS-7 cells inhibits the transcriptional activity of SRE and AP-1 which
      may be silenced by siRNA. These results suggest that ZNF418 is a member of the
      zincfinger transcription factor family and may act as a negative regulator in
      MAPK signaling pathway.

PMID- 18084725
TI  - Vascular networks in retinal arterial macroaneurysms.
AB  - Retinal arterial macroaneurysms (MA) are a rare pathology, often associated with
      old age, arterial hypertension, artherosclerosis, and retinal vein occlusions.
      Here, we present two unusual cases of MA in patients with arterial hypertension,
      that displayed small vascular networks at the site of the MA on angiography.
      Resulting exudative changes and the networks themselves regressed after laser
      treatment, and visual acuity improved. Those vascular networks might represent
      collateral vessels forming as a rare sequel after spontaneous occlusion of the
      MA.

PMID- 18084726
TI  - QT prolongation: a case of arsenical pericardial and pleural effusion.
AB  - Arsenic trioxide is an effective treatment for patients with acute promyelocytic
      leukaemia (APL) who have relapsed from or are refractory to all trans-retinoic
      acid and anthracycline chemotherapy. Cardiac effects observed include
      electrocardiographic changes such as QTc prolongation, T-wave abnormalities,
      torsades de pointes and sudden death. We describe a case of a man, 76 years old,
      who was admitted to our department for dyspnoea in APL in treatment with arsenic
      trioxide. Chest radiograph illustrated an enlarged cardiac silhouette and
      bilateral pleuric effusion and the ECG evidenced QT prolongation. The patient was
      also submitted to transthoracic echocardiography that revealed moderate
      pericardial effusion without signs of cardiac tamponade and a normal
      biventricular function. This condition was considered to be associated with
      arsenic trioxide polyserosit and the drug therapy was immediately discontinued
      and steroid drugs started. After 2 weeks of arsenic trioxide therapy suspension
      there was evidence of complete resolution of pericardial and pleuric effusion and
      the ECG showed normal QT interval.

PMID- 18084727
TI  - Hemispheric differences in cerebral autoregulation in children with moderate and
      severe traumatic brain injury.
AB  - INTRODUCTION: To examine hemispheric differences in cerebral autoregulation in
      children with traumatic brain injury (TBI). After IRB approval and consent,
      subjects underwent static cerebral autoregulation testing during the first 9 days
      after PICU admission. Cerebral autoregulation was quantified using the
      autoregulatory index (ARI). RESULTS: Forty-two (27 M:15 F) children (10 +/- 5
      years) with TBI and admission Glasgow coma scale score (5 +/- 2) were enrolled.
      Seven (54%) of the 13 children with focal TBI and 8 (28%) of 29 children with
      diffuse TBI had impairment or absence of cerebral autoregulation of at least one
      hemisphere. In patients with isolated focal TBI, ARI was lower (0.40 +/- 0.40 vs.
      0.67 +/- 0.40; P = 0.03) in the side of TBI than in the unaffected hemisphere,
      but cerebral autoregulation was often impaired on the side without TBI or shift
      (5/13) on head CT. There was no difference in ARI between hemispheres in children
      with diffuse TBI, with or without superimposed focal lesions (P = 0.17). Patients
      with bilateral intact cerebral autoregulation tended to have higher 6 month
      Glasgow Outcome Score (GOS) than patients with either unilateral or bilateral
      cerebral autoregulation impairment (GOS 4.0 +/- 0.60 vs. 3.6 +/- 0.80; P = 0.08).
      CONCLUSIONS: Hemispheric differences in cerebral autoregulation were common in
      children with isolated focal TBI. Absence of TBI on CT was not always associated
      with intact cerebral autoregulation. Patients with bilaterally intact cerebral
      autoregulation tended to have better outcomes.

PMID- 18084728
TI  - Effects of caudal fourth ventricular lactate infusion on hypoglycemia-associated
      MCT2, GLUT3, GLUT4, GCK, and sulfonylurea receptor-1 gene expression in the
      ovariectomized female rat LHA and VMH: impact of estradiol.
AB  - Cellular metabolic stasis is monitored in the lateral hypothalamic area (LHA) and
      ventromedial hypothalamic nucleus (VMH), the classically defined hypothalamic
      "anoretic" and "satiety" centers, respectively. Neuronal glucose (GLUT3, GLUT4)
      and monocarboxylate (MCT2) transporter genes are expressed in both sites,
      suggesting that glucose and lactate, a product of astrocytic glycolysis, may fuel
      aerobic respiration in local neurons. Evidence that glucose utilization in the
      hypothalamus, but not other brain regions, is reported to vary according to
      cyclic estradiol secretion suggests that this hormone may regulate uptake and/or
      catabolism of this fuel. We investigated the hypothesis that estradiol exerts
      site-specific regulatory effects on basal and insulin-induced hypoglycemia (IIH)
      associated MCT2 and neuronal glucose transporter mRNA profiles, and expression of
      genes that encode the substrate sensor, glucokinase (GCK), and the sulfonylurea
      receptor-1 (SUR) subunit of the energy-dependent potassium channel, K(ATP), in
      the female rat LHA and VMH. As caudal fourth ventricular (CV4) lactate infusion
      intensifies hypoglycemia in this gender, we also examined whether demonstrable
      LHA and VMH gene responses to IIH are correspondingly amplified. MCT2, GLUT3,
      GLUT4, GCK, and SUR1 mRNA levels in the LHA and VMH did not differ between saline
      injected ovariectomized (OVX) rats implanted with estradiol benzoate (EB) or oil
      (O). LHA: IIH had no impact on gene profiles, excluding SUR1, in EB-treated
      animals, but decreased these transcripts, with the exception of GCK, in OVX + O
      rats. CV4 lactate infusion in hypoglycemic OVX + EB animals suppressed each mRNA
      profile, but reversed IIH-associated reductions in MCT2, GLUT3, and GLUT4 gene
      expression in OVX + O. VMH: IIH increased MCT2 and GLUT4 transcripts in OVX + EB,
      but not OVX + O rats and decreased GCK mRNA in both groups. Lactate plus insulin
      treatment elevated VMH MCT2, GLUT3, SUR1, and GCK gene expression in EB- and O
      implanted OVX rats, but augmentation of the former three profiles was greater in
      the presence of EB. The data show that LHA and VMH neurons exhibited dissimilar,
      estradiol-dependent adjustments in neuronal lactate and glucose transporter, GCK,
      and SUR1 gene expression during IIH, and that in the presence of estradiol,
      caudal hindbrain lactate infusion during IIH elicited divergent changes in MCT2,
      GLUT3, GCK, and SUR1 gene expression in the LHA and VMH, where these transcripts
      were, respectively, diminished or augmented. These results support the need to
      investigate the potential impact of site-specific adjustments in fuel uptake and
      KATP regulation of membrane voltage on general and specialized, e.g.,
      chemosensory, neuronal functions.

PMID- 18084729
TI  - Magnetic resonance imaging in the evaluation of central nervous system
      manifestations in systemic lupus erythematosus.
AB  - Central nervous system (CNS) manifestations are often observed in systemic lupus
      erythematosus (SLE) patients during the course of their disease. The prevalence
      of CNS manifestations ranges between 17 and 75%, reflecting different methods of
      patient selection and assessment, varying levels of assessor expertise, and lack
      of a consensus for diagnosing active and chronic neuropsychiatric (NP)
      manifestations. Postulated pathogenic mechanisms of peripheral and CNS events
      include vasculopathy, autoantibody effects, and systemic inflammation. Diagnosis
      is often difficult because of the lack of standardized diagnostic techniques.
      Magnetic resonance imaging (MRI) is considered the gold standard for the
      evaluation of CNS manifestations in SLE patients in clinical practice. MRI
      findings are diverse, and atrophy and hyperintense white matter lesions often
      correlate poorly with clinical manifestations, occurring also in patients without
      marked CNS signs and symptoms. We will describe MRI findings in SLE patients and
      discuss the usefulness of different MRI techniques in evaluating acute and
      chronic CNS manifestations.

PMID- 18084730
TI  - Radiofrequency thermal ablation of metastatic neuroendocrine tumors in the liver.
AB  - In our armamentarium against neuroendocrine hepatic metastases, radiofrequency
      thermal ablation has proven to play a valuable role. Patients with neuroendocrine
      malignancies that progress to hepatic metastases may suffer not only from the
      hormonal sequelae of their disease, but also face the specter of death within
      several years from progressive hepatic replacement. For the majority of these
      patients who are not surgical candidates due to the extent of liver involvement,
      radiofrequency thermal ablation represents a low-risk treatment modality
      effective at both symptom alleviation and survival prolongation. Utilizing a
      laparoscopic approach guided by intra-operative ultrasound, effective tumor
      ablation can be achieved with minimal morbidity and low rates of local tumor
      recurrence.

PMID- 18084732
TI  - Nutritional characterisation of foods: science-based approach to nutrient
      profiling. Summary report of an ILSI Europe workshop held in April 2006.
AB  - The background of the workshop was the proposed EU legislation to regulate
      nutrition and health claims for foods in Europe. This regulation will require the
      development of a science-based nutrient profiling system in order to determine
      which foods or categories of foods will be permitted to make nutrition or health
      claims. Nutrient profiling can also be used to categorize foods, based on an
      assessment of their nutrient composition according to scientific principles.
      Today, various nutrient profiling schemes are available to classify foods based
      on their nutritional characteristics. The aim of the workshop was to discuss the
      work developed by ILSI Europe's expert group and to explore wider scientific
      aspects of nutrient profiling, including their relative effectiveness, strengths
      and weaknesses. In particular, the focus of the workshop was on scientific
      approaches to the development of nutrient profiles for the purpose of regulating
      nutrition and health claims. The 76 workshop participants were scientists from
      European academic institutions, research institutes, food standards agencies,
      food industry and other interested parties, all of whom contributed their
      thinking on this topic. The workshop reached a degree of agreement on several
      central points. Most participants favored a food category approach rather than an
      'across the board' system for nutrient profiling. Most also felt that nutrient
      profiling schemes should focus on disqualifying nutrients, while taking into due
      account relevant qualifying nutrients. Levels of each nutrient should be clearly
      defined for all food categories to be profiled. Reference amounts selected for
      further considerations were: (1) per 100 g/100 ml, (2) legislated reference
      amounts, and (3) per 100 kcal. The majority of workshop participants agreed that
      nutrient profiling schemes should allow for a two-step decision process; step (1)
      identify which nutrients to take into account, and step (2) define the thresholds
      for these nutrients. All participants agreed that an objective validation should
      be conducted before implementation of nutrient profiling. This would include
      determination of sensitivity and specificity using "indicator foods" selected on
      their potential to affect major health issues. The management of any adopted
      system needs to allow it to be dynamic over time and revise the system when new
      scientific knowledge emerges. The majority of participants favored a food
      category approach rather than an 'across the board' system. Further work is
      required to identify the final list of qualifying and disqualifying nutrients for
      any food category that may be identified and for the selection of optimal
      reference amounts. It is essential that key stakeholders continue to communicate
      and work together on the complex issues of nutrient profiling.

PMID- 18084733
TI  - Nutrient profiling schemes: overview and comparative analysis.
AB  - Nutrient profiling is a discipline aimed at classifying foods based on their
      nutritional composition. So far, several profiling schemes have been proposed for
      varied purposes world-wide. Primary aim to inventory the main profiling schemes
      that have been developed so far (both applied and not) and to summarise their
      main aspects. Secondary aim to critically review a selection of them, to test
      their "performance" and to evaluate their strengths and weaknesses. Scientific
      and popular search engines were used for identifying profiling schemes. Schemes
      were described concisely by providing details on four main "Building Blocks" or
      factors: (1) Food category declination: category-wise or "across the board"; (2)
      Reference amount: 100 g, 100 kcal; serving; (3) Cut-off use: thresholds or
      scores; (4) Nutrients Selection: balance between positive and negative nutrients
      and number of them. The "performance" analysis was done by testing how the
      selected schemes classify a sample of food. Profiling schemes display
      considerable variation based on the underlying approach, format and content.
      Moreover, the rationale of the schemes largely varies and seems to be inspired by
      either nutrient recommendations or regulations figures. When tested for
      "performance", the five selected schemes classify in the same way foods having
      either a very "positive" or a very "negative" nutrient profile, whereas they give
      inconsistent results for food products with intermediate characteristics.
      Strengths and weaknesses analysis shows the difficulty of finding schemes
      combining qualities such as simplicity, scientific relevance, ability to cope
      with changes in nutrient recommendations. Current proposed profiling schemes
      exhibit a wide range of differences both in terms of approaches and
      "performance". Nutrition scientists have now the challenge to develop the "ideal
      scheme" that, in our view, will have to be strict enough to ensure consumer
      protection but also flexible enough to encourage food industry innovation and to
      promote a "healthy" competitive market.

PMID- 18084734
TI  - A new reference method for the validation of the nutrient profiling schemes using
      dietary surveys.
AB  - Nutrient profiles of foods are increasingly used as the scientific basis of
      nutritional labeling, health claims, or nutritional education. Nutrient profiling
      schemes are based on sets of rules, scores, or thresholds applied to the
      nutritional composition of foods. However, there is a lack of scientific
      validation of nutritional profiling schemes. To develop a reference method using
      existing dietary surveys, to define a set of indicator foods that are positively
      or negatively associated with a "healthy diet." Such indicator foods can be used
      both for establishing relevant nutrient profiles and for the validation of
      existing or future nutrient profiling schemes. The proposed validation method is
      based on food and nutrient intakes of adults participating in national dietary
      surveys in five EU countries: Belgium (n = 2,507), Denmark (n = 3,151), France (n
      = 1,474), Ireland (n = 1,379), and Italy (n = 1,513). The characterization of
      indicator foods is divided in two steps. First, "healthy diets" of individuals
      are identified in the five national dietary surveys by comparison to the Eurodiet
      reference intakes. Second, indicator foods associated positively or negatively to
      the "healthy diets" are determined. With a P-value of 10(-3) for the test of
      comparison of food intakes between the "most healthy eaters" and the "less
      healthy eaters," it was possible to identify 294 indicator foods out of 1,669
      foods tested in the five countries. In all the countries except Italy, there were
      more indicator foods positively associated than indicator foods negatively
      associated with the "healthy diet." The food categories of these indicator foods
      were in good agreement with Food Based Dietary Guidelines like the USDA dietary
      guideline for Americans. A new reference method for the validation of profiling
      schemes was developed based on dietary intake data from using dietary surveys in
      five European countries. Only a minority of foods consumed in these dietary
      surveys could be used as indicator foods of healthy or unhealthy diets in order
      to subsequently test nutritional profiling schemes. Further work is needed to
      build a list of indicator foods that could be considered as a "gold standard."

PMID- 18084735
TI  - Comparison of different nutrient profiling schemes to a new reference method
      using dietary surveys.
AB  - A new EU regulation on nutrition and health claims made on foods has entered into
      force in January 2007. The regulation provides for the use of nutrient profiles
      to determine which foods may bear claims but does not specify what the profiles
      should be or how they should be developed. Several nutrient profiling schemes
      have already been established. Therefore, it is necessary to develop approaches
      to test if the existing profiling schemes could fulfil the new regulation needs.
      The aim of the present study is to investigate how reference "indicator foods"
      derived from national dietary surveys in five different countries, are classified
      according to three existing nutrient profiling schemes: The UK Food Standards
      Agency (FSA) model, The Dutch Tripartite classification model and the US FDA
      model used for regulating health claims. "Indicator foods" that have been shown
      to be positively or negatively associated with healthy diets in adults in five EU
      countries were classified according to each of the three profiling schemes. The
      performance and effectiveness of each profiling scheme in correctly classifying
      the "indicator foods" were assessed using sensitivity and specificity ratios. The
      sensitivity and the specificity ratios of the three profiling schemes tested were
      relatively good. There were only small differences of performance between the
      three systems. A significant negative correlation between sensitivity and
      specificity was observed. The level of concordance between the classification of
      the "indicator foods" that have been selected because of being positively or
      negatively associated with a healthy diet and the classification by each of the
      three profiling methods tested was quite good. However, further improvement of
      the "indicator foods" approach is needed if it is to serve as a "gold standard".

PMID- 18084736
TI  - The ins and outs of lipid efflux.

PMID- 18084737
TI  - Tissue-specific induction of ADAMTS2 in monocytes and macrophages by
      glucocorticoids.
AB  - The regulated expression of ADAMTS2 (a disintegrin and metalloproteinase with
      thrombospondin motifs), a secreted metalloproteinase involved in the processing
      of procollagen to collagen, was studied in peripheral blood mononuclear cells
      (PBMC). Stimulation with glucocorticoids (GC) resulted in a pronounced dose- and
      time-dependent increase of ADAMTS2 mRNA levels in PBMC. The increase of ADAMTS2
      expression was specific for CD14++ monocytes (440-fold) and alveolar macrophages
      (200-fold), whereas CD3+ (T lymphocytes), phytohemagglutinin-activated CD3+ (T
      lymphocytes), and CD19+ (B lymphocytes) showed no significant changes in ADAMTS2
      mRNA after GC treatment. Treatment of monocyte-derived macrophages (MDM) with GC
      also resulted in an increase of ADAMTS2 protein in the culture tissue media.
      Using the GC analog RU486, GC-mediated induction of ADAMTS2 mRNA was blocked,
      implicating that GC acts specifically via the GC-receptor. In agreement with
      findings in blood monocytes, cell lines of the monocytic lineage (MM6, THP-1)
      showed significant GC-induced significant increases in ADAMTS2 mRNA, while in
      epithelial cells (A549, Calu-3, Colo320, BT-20) and fibroblast (MRC-5, WI-38, and
      two NHDF-c cell types from adult cheek and upper arm), they showed no or little
      responsiveness to GC. As macrophages have important functions in immune defense
      and tissue homeostasis, these findings suggest that GC-mediated specific
      induction of ADAMTS2 in these cells may play a crucial role in the resolution of
      inflammation and wound repair.

PMID- 18084738
TI  - [Perspectives in urinary diversion].
AB  - "Perspectives in Urinary Diversion" was the title of a presentation held during
      the opening session of the 56th annual meeting of the German Urological
      Association in Hamburg on September 21, 2006. It focused on the balance between
      obstruction and reflux of ureters implanted in diverted intestinal segments, the
      choice of intestinal segments for orthotopic pouches, orthotopic diversion in the
      female, the status of rectal diversions, and alternatives to the use of
      intestinal segments.

PMID- 18084739
TI  - [Fibrous dysplasia].
AB  - Fibrous dysplasia is a tumorlike, benign lesion, caused by sporadic mutation
      during early embryogenesis. The skeletal involvement becomes increasingly visible
      during growth. The number and extent of dysplastic lesions increase until the age
      of 15. The polyostotic form is often associated with endocrine dysfunction, which
      should be diagnosed and treated early. Malignant transformation of fibrous
      dysplastic lesions is less than 1%; therefore, treatment or resection of the
      lesion itself is not necessary. The progress of the lesions during growth can
      lead to pain, fractures, and deformities. Bisphosphonates are effective for pain
      relief, but have no assured effect on the natural history of the disease.
      Fracture healing is not compromised by the disease. Conservative treatment with
      casts is therefore effective, especially for the upper limbs. The surgical
      approach with deformity correction and stabilization remains challenging
      particularly with regard to the proximal femur. Intramedullary devices should be
      preferred to plates, if possible.

PMID- 18084740
TI  - Structural analysis of cell wall mannan of Candida sojae, a new yeast species
      isolated from defatted soybean flakes.
AB  - We investigated the structural and immunochemical characteristics of cell wall
      mannan obtained from Candida sojae JCM 1644, which is a new yeast species
      isolated from defatted soybean flakes. The results of a slide-agglutination test
      and of an enzyme-linked immunosorbent assay using anti-factor sera to the
      pathogenic Candida species indicated that the cells and the C. sojae mannan were
      cross-reactive to the specific anti-factor sera against Candida albicans serotype
      A (FAb 6) and Candida guilliermondii (FAb 9). Two-dimensional homonuclear
      Hartmann-Hahn analysis indicated that the mannan consisted of various linked
      oligomannosyl side chains containing alpha-1,2-, alpha-1,3-, alpha-1,6- and beta
      1,2-linked mannose residues. However, although the determinants of antigenic
      factors 6 and 9 could be not found in this mannan, branched side chains, Manbeta1
      2Manalpha1-3[Manalpha1-6]Manalpha1-(2Manalpha1-)n2Man and a linear alpha-1,6
      linked polymannosyl backbone, which are cross-reacted by FAbs 6 and 9,
      respectively, were identified. The mannan was subjected to acetolysis in order to
      determine the polymerization length of the alpha-1,2-linked oligomannosyl residue
      in the side chains. The result of (1)H-nuclear magnetic resonance analysis of the
      released oligosaccharides showed that the remarkable regularity in the length of
      alpha-1,2-linked oligomannosyl side chains, which were previously found in
      mannans of other Candida species, is not observed in this mannan.

PMID- 18084741
TI  - S-Adenosylmethionine induces BldH and activates secondary metabolism by involving
      the TTA-codon control of bldH expression in Streptomyces lividans.
AB  - In the present study, a mechanism for S-adenosylmethionine (SAM) to promote
      secondary metabolism was characterized in terms of bldH sl) expression in
      Streptomyces lividans. A previous study demonstrated that SAM, on application at
      2 microM, induces the transcription of the strR promoter (strRp), which
      originates from Streptomyces griseus, in S. lividans. An inactivation study
      verified that bldH sl is essential to strRp transcription in S. lividans and it
      was demonstrated that the effects of SAM on the induction of strRp activity, on
      the transcription of redZ and actII-orf4, and on antibiotic production were
      compromised when the unique leucine TTA-codon of bldH sl was changed to TTG.
      Western blot analysis revealed that SAM supplementation enhances the expression
      of bldH sl when the TTA-codon was intact but not when the TTG replacement was
      provided. This study validates the involvement of BldH sl in the potentiating
      effect of SAM on the antibiotic production and substantiates that SAM controls
      the expression of bldH sl through the TTA-codon control in translating bldH mRNA.
      It is argued here that the intracellular SAM-level modulates the maturation of
      bldA, which encodes the UUA-codon tRNA and controls secondary metabolism in S.
      lividans.

PMID- 18084742
TI  - Cordycepin (3'-deoxyadenosine) inhibits the growth of B16-BL6 mouse melanoma
      cells through the stimulation of adenosine A3 receptor followed by glycogen
      synthase kinase-3beta activation and cyclin D1 suppression.
AB  - Cordyceps sinensis, a parasitic fungus on the larvae of Lepidoptera, has been
      used as a traditional Chinese medicine. We previously reported that the growth of
      B16-BL6 mouse melanoma (B16-BL6) cells was inhibited by cordycepin (3'
      deoxyadenosine), an active ingredient of C. sinensis, and its effect was
      antagonized by MRS1191, a selective adenosine A3 receptor antagonist. In this
      study, the radioligand binding assay using [125I]-AB-MECA (a selective adenosine
      A3 receptor agonist) has shown that B16-BL6 cells express adenosine A3 receptors
      and that cordycepin binds to these receptors. We also confirmed the involvement
      of adenosine A3 receptors in the action of cordycepin using MRS1523 and MRS1220,
      specific adenosine A3 receptor antagonists. Next, indirubin, a glycogen synthase
      kinase-3beta (GSK-3beta) inhibitor, antagonized the growth suppression induced by
      cordycepin. Furthermore, the level of cyclin D1 protein in B16-BL6 cells was
      decreased by cordycepin using Western blot analysis. In conclusion, this study
      demonstrated that cordycepin inhibits the proliferation of B16-BL6 cells by
      stimulating adenosine A3 receptors followed by the Wnt signaling pathway,
      including GSK-3beta activation and cyclin D1 inhibition.

PMID- 18084743
TI  - Effect of varenicline and bupropion SR on craving, nicotine withdrawal symptoms,
      and rewarding effects of smoking during a quit attempt.
AB  - AIMS: To examine the effect of varenicline, a selective alpha4-beta2 nicotinic
      acetylcholine receptor (nAChR) partial agonist, on craving and withdrawal
      symptoms in smokers making a quit attempt and the rewarding effects of smoking
      during a lapse after the target quit date (TQD). MATERIALS AND METHODS: Pooled
      data were analysed from two identical double-blind, randomised trials comparing
      varenicline 1 mg BID, bupropion (sustained release) 150 mg BID and placebo using
      measures of craving and withdrawal in the first week after the TQD (in abstinent
      [n = 612] and non-abstinent participants [n = 1,155]) and of the rewarding
      effects of the first cigarette smoked in non-abstinent participants. RESULTS: In
      abstinent and non-abstinent participants combined, varenicline reduced craving
      more than bupropion (p < 0.01) and placebo (p < .001); the effect did not differ
      by whether or not subjects were abstinent; bupropion reduced craving more than
      placebo (p < 0.001). Among abstinent participants, both varenicline and bupropion
      reduced negative affect more than those receiving placebo (p < 0.005). Neither
      active drug reduced restlessness, insomnia or appetite vs placebo. Varenicline
      reduced ratings of satisfaction and psychological reward after the first
      cigarette smoked after the TQD vs bupropion (p < 0.005) and placebo (p < 0.001);
      bupropion also reduced these more than placebo (p < 0.05). CONCLUSIONS:
      Varenicline significantly reduces craving and the rewarding effects of smoking
      after the TQD to a greater extent than bupropion, which may contribute to
      varenicline's greater efficacy for smoking cessation. Varenicline's lack of
      effect in reducing insomnia, restlessness and increased appetite in this analysis
      suggests that receptors other than the alpha4-beta2 nAChR subtype may be
      implicated in these withdrawal symptoms.

PMID- 18084744
TI  - Stimulant alcohol effects prime within session drinking behavior.
AB  - RATIONALE: Individual differences in subjective alcohol effects have been shown
      to differ by risk status (e.g., family history of alcoholism) and to predict
      future risk for alcohol-related problems. Presumably, individual differences in
      both stimulant and sedative responses affect the rewarding value of drinking
      which, in turn, impacts future drinking behavior. Although plausible, this
      theoretical model is largely untested. OBJECTIVES: The current study attempted to
      provide experimental evidence for the impact of subjective alcohol responses on
      within session drinking behavior. MATERIALS AND METHODS: Using a placebo
      controlled between-subjects alcohol administration paradigm, experiences and
      evaluations of stimulant and sedative alcohol effects (after a target dose of
      0.06 g%) were assessed as predictors of ad-libitum consumption in the context of
      anticipatory stress. RESULTS: Analyses indicated that an initial dose of alcohol
      increased experiences of both stimulation and sedation although stimulant effects
      were evaluated much more positively. In addition, stimulant effects after a
      priming dose predicted further consumption, whereas sedative effects did not.
      CONCLUSIONS: At least among moderate to heavy drinking college students,
      stimulant alcohol effects are more reinforcing and predict within session
      drinking behavior under social stress. Increased attention should be given to
      stimulant alcohol effects as a risk factor for excessive consumption in this
      population. Incorporating information about stimulant alcohol effects in
      prevention and intervention programs may also be important if additional research
      supports the current results.

PMID- 18084745
TI  - Effects of chronic treatment with citalopram on cannabinoid and opioid receptor
      mediated G-protein coupling in discrete rat brain regions.
AB  - RATIONALE: There is growing interest in investigating the mechanisms of action of
      selective serotonin reuptake inhibitors (SSRIs), beyond their association with
      the serotonergic system, due to their wide therapeutic potential for disorders
      including depression, pain and addiction. OBJECTIVE: The aim of this study was to
      investigate whether chronic treatment with the SSRI, citalopram, alters the
      functional coupling of G(i/o)-associated cannabinoid type 1 (CB(1)) and mu-opioid
      receptors in selected areas of rat brain implicated in psychiatric disorders and
      pain. METHODS: Using an autoradiographic approach, the effects of the cannabinoid
      receptor agonist, HU210 (in the presence or absence of the CB(1) receptor
      antagonist AM251), or the mu-opioid receptor agonist, [D: -Ala(2),N-Me
      Phe4,Gly(5)-ol]-enkephalin (DAMGO; in the presence or absence of the mu-opioid
      receptor antagonist D: -Phe-Cys-Tyr-D: -Trp-Orn-Thr-Pen-Thr-NH(2)), on
      [(35)S]GTPgammaS binding in discrete brain regions of citalopram-treated (10 mg
      kg(-1) day(-1) for 14 days by subcutaneous minipump) and control rats were
      investigated. RESULTS: The HU210-induced increase in [(35)S]GTPgammaS binding
      observed in the hypothalamic paraventricular nucleus of control rats was
      abolished after chronic treatment with citalopram. Reduced response to HU210 in
      rats receiving chronic treatment with citalopram was also observed in the
      hippocampus and medial geniculate nucleus. Citalopram had no significant effect
      on DAMGO-induced [(35)S]GTPgammaS binding in the brain regions investigated, with
      the exception of the medial geniculate nucleus where a modest impairment was
      observed. CONCLUSIONS: These data provide evidence for reduced cannabinoid
      receptor-mediated G-protein coupling in the hypothalamus, hippocampus and medial
      geniculate nucleus of rats chronically treated with citalopram, effects which
      may, in part, underlie the mechanism of action of SSRIs.

PMID- 18084746
TI  - Characterization of polyvinyl resins used as binding media in paintings by
      pyrolysis-silylation-gas chromatography-mass spectrometry.
AB  - Polyvinyl resins, in particular poly(vinyl acetate) emulsions (PVA), are widely
      used in contemporary paintings as binding media, because of the optimum
      mechanical and optical properties these polymers confer on the paint layers. A
      study has been carried out to chemically characterize samples of PVA resins
      prepared as coating films from commercial products currently available from fine
      arts suppliers. For this purpose, a new method has been based on "on-line"
      silylation-pyrolysis using hexamethyldisilazane as derivatisation reagent in
      pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS). This proposed
      procedure leads to unambiguous identification of this type of binder and improves
      conventional direct Py-GC-MS. PVA media used in three contemporary paintings from
      a private collection and from the Museum of Fine Arts of Malaga (Spain) have been
      successfully identified with this procedure. As a second step of this work, a
      study devoted to the characterization of changes in the chemical composition of
      the PVA commercial products studied has been carried out. Effects induced in the
      specimens by three different types of artificial accelerated ageing process-
      thermal, UV light, and in an SO(2)-polluted chamber--were compared.

PMID- 18084747
TI  - Determination of marine biotoxins relevant for regulations: from the mouse
      bioassay to coupled LC-MS methods.
AB  - The frequency of occurrence and intensity of harmful algal blooms (HABs) appear
      to be increasing on a global scale. Consequently, methods were established for
      the evaluation of possible hazards caused by the enrichment of algal toxins in
      the marine food chain. Different clinical types of algae-related poisoning have
      attracted scientific attention: paralytic shellfish poisoning (PSP), diarrhetic
      shellfish poisoning (DSP), and amnesic shellfish poisoning (ASP). In several
      countries fish specialties are consumed which may be contaminated with algal
      toxins typical for the respective region (e.g., ciguatera and tetrodotoxins).
      Bioassays are common methods for the determination of marine biotoxins. However,
      biological tests are not completely satisfactory, due to the low sensitivity and
      the absence of specialized variations. Moreover, there is growing resistance
      against the use of animal experiments. Therefore, many efforts have been made to
      determine algal toxins with chemical methods. In this context LC-MS methods
      replaced HPLC methods with optical detectors, allowing both effective seafood
      control and monitoring of phytoplankton in terms of the different groups of
      marine biotoxins.

PMID- 18084748
TI  - Development of an osteoblast-based 3D continuous-perfusion microfluidic system
      for drug screening.
AB  - In this work, we demonstrated that biological cells could be cultured in a
      continuous-perfusion glass microchip system for drug screening. We used mouse
      Col1a1GFP MC-3T3 E1 osteoblastic cells, which have a marker gene system
      expressing green fluorescent protein (GFP) under the control of osteoblast
      specific promoters. With our microchip-based cell culture system, we realized
      automated long-term monitoring of cells and sampling of the culture supernatant
      system for osteoblast differentiation assay using a small number of cells. The
      system successfully monitored cells for 10 days. Under the 3D microchannel
      condition, shear stress (0.07 dyne/cm(2) at a flow rate of 0.2 microL/min) was
      applied to the cells and it enhanced the GFP expression and differentiation of
      the osteoblasts. Analysis of alkaline phosphatase (ALP), which is an enzyme
      marker of osteoblasts, supported the results of GFP expression. In the case of
      differentiation medium containing bone morphogenetic protein 2, we found that ALP
      activity in the culture supernatant was enhanced 10 times in the microchannel
      compared with the static condition in 48-well dishes. A combined system of a
      microchip and a cell-based sensor might allow us to monitor osteogenic
      differentiation easily, precisely, and noninvasively. Our system can be applied
      in high-throughput drug screening assay for discovering osteogenic compounds.

PMID- 18084749
TI  - Can we trust mass spectrometry for determination of arsenic peptides in plants:
      comparison of LC-ICP-MS and LC-ES-MS/ICP-MS with XANES/EXAFS in analysis of
      Thunbergia alata.
AB  - The weakest step in the analytical procedure for speciation analysis is
      extraction from a biological material into an aqueous solution which undergoes
      HPLC separation and then simultaneous online detection by elemental and molecular
      mass spectrometry (ICP-MS/ES-MS). This paper describes a study to determine the
      speciation of arsenic and, in particular, the arsenite phytochelatin complexes in
      the root from an ornamental garden plant Thunbergia alata exposed to 1 mg As L(
      1) as arsenate. The approach of formic acid extraction followed by HPLC-ES-MS/ICP
      MS identified different As(III)-PC complexes in the extract of this plant and
      made their quantification via sulfur (m/z 32) and arsenic (m/z 75) possible.
      Although sulfur sensitivity could be significantly increased when xenon was used
      as collision gas in ICP-qMS, or when HR-ICP-MS was used in medium resolution, the
      As:S ratio gave misleading results in the identification of As(III)-PC complexes
      due to the relatively low resolution of the chromatography system in relation to
      the variety of As-peptides in plants. Hence only the parallel use of ES-MS/ICP-MS
      was able to prove the occurrence of such arsenite phytochelatin complexes.
      Between 55 and 64% of the arsenic was bound to the sulfur of peptides mainly as
      As(III)(PC(2))(2), As(III)(PC(3)) and As(III)(PC(4)). XANES (X-ray absorption
      near-edge spectroscopy) measurement, using the freshly exposed plant root
      directly, confirmed that most of the arsenic is trivalent and binds to S of
      peptides (53% As-S) while 38% occurred as arsenite and only 9% unchanged as
      arsenate. EXAFS data confirmed that As-S and As-O bonds occur in the plants. This
      study confirms, for the first time, that As-peptides can be extracted by formic
      acid and chromatographically separated on a reversed-phase column without
      significant decomposition or de-novo synthesis during the extraction step.

PMID- 18084750
TI  - Characterizing the interaction between aptamers and human IgE by use of surface
      plasmon resonance.
AB  - Human immunoglobulin E (hIgE) is such an important protein, because of its
      involvement in allergic disease, that it is of significance to study the
      interactions between it and its recognizing elements. In this report an
      analytical strategy based on surface plasmon resonance (SPR) was developed to
      probe the pattern of interaction between hIgE and its recognizing molecules,
      including aptamers and antibodies. The affinity constants of hIgE for the
      antibody and the aptamer were compared first; the aptamer has more affinity than
      the antibody for human IgE. To study their pattern of interaction, three
      different binding approaches, including adding the antibody and the streptavidin
      coupled aptamer to the sensing surface, were designed. The results showed that
      hIgE captured on the sensing surface could form a multivalent complex with the
      aptamer. An ELISA-like assay using the aptamer as both capture and detection
      probes was then developed. This work highlights an SPR method for characterizing
      the interaction between the protein and aptamers that is useful for study of
      biomolecular interaction patterns and binding properties.

PMID- 18084752
TI  - Reviewing the process of preparing children for MRI.
AB  - BACKGROUND: MRI is a common medical imaging investigation. Patients, including
      young children, can be required to keep still for up to 60 min for the study to
      be completed successfully. Children often find the confined space, noise, need to
      lie still and possibility of intravenous administration of contrast agent anxiety
      provoking and sometimes so distressing that they are unable to cope and require
      general anaesthesia. OBJECTIVE: A practice MRI intervention was introduced at the
      Royal Children's Hospital in Melbourne, Australia. The program is conducted by
      educational play therapists in conjunction with the Department of Medical
      Imaging. This study explored the effectiveness of this intervention. MATERIALS
      AND METHODS: The intervention was conducted in a practice MRI unit devoid of
      magnets. Data were collected as a clinical audit with respect to age, gender,
      times of scans, position in bore, diagnostic scans and movement artefact. Epidata
      and Stata were used to analyze the data. RESULTS: A total of 291 children were
      included; their ages ranged from 3 years 7 months to 17 years (mean 7.9 years),
      and 48.8% were male. Of the 291 children, 218 (74.9%) were considered a pass at
      practice, 35 (12 %) were considered borderline pass, and diagnostic images were
      obtained from 218 (96%) of those children who went onto a clinical MRI.
      CONCLUSION: We conclude that practice MRI intervention facilitated by educational
      play therapists is a useful intervention in supporting children to cope with MRI
      without general anaesthesia.

PMID- 18084751
TI  - Intradural spinal tumors: current classification and MRI features.
AB  - The differential diagnosis of intradural spinal tumors is primarily based on
      location, but the clinical presentation, age, and gender of the patient are also
      important factors in determining the diagnosis. This comprehensive review focuses
      on the current classification, clinical symptoms, and MRI features of the more
      common intradural extramedullary and intramedullary neoplastic lesions. This
      review does not include extradural lesions.

PMID- 18084753
TI  - Recurrent midgut volvulus following a Ladd procedure.
AB  - We present a case of recurrent midgut volvulus in a 3-year-old girl with a
      history of midgut volvulus repair as an infant. Awareness of the possibility of
      recurrence even several years following an initial Ladd procedure is crucial to
      ensure prompt treatment in these children.

PMID- 18084754
TI  - Hyperechoic metaphyses in hypophosphatasia: what does it mean?
AB  - We report a case of hypophosphatasia diagnosed using US and CT at 29 weeks'
      gestation and confirmed by molecular analysis. Prenatal US revealed very short
      fetal limbs and severe demineralization of the skull. The diaphyses were normal,
      but the metaphyses of the long bones appeared hyperechoic with no posterior
      shadowing. No fractures or long-bone deformations were observed. Three
      dimensional helical CT performed at 29 weeks' gestation provided additional
      details of the abnormal bones, i.e. irregular and cupped metaphyses that were
      very similar to the radiological findings of hypophosphatasia described
      postnatally. To our knowledge, the description of hyperechoic metaphyses in
      hypophosphatasia is unique and is a consequence of abnormal mineralization of the
      metaphyses that is specific to this pathology.

PMID- 18084755
TI  - Accelerated decolorization of structurally different azo dyes by newly isolated
      bacterial strains.
AB  - Wastewater effluents from the textile and other dye-stuff industries contain
      significant amounts of synthetic dyes that require treatment to prevent
      groundwater contamination. In research aimed at biotechnology for treatment of
      azo dyes, this study examined 288 strains of azo-dye degrading bacteria to
      identify efficient strains and determine incubation times required for
      decolorization. Initial enrichment cultures were carried out using a mixture of
      four structurally different dyes (Acid Red 88, Reactive Black 5, Direct Red 81,
      and Disperse Orange 3) as the sole source of C and N to isolate the bacteria from
      soil, activated sludge, and natural asphalt. Six strains were selected for
      further study based on their prolific growth and ability to rapidly decolorize
      the dyes individually or in mixtures. Treatment times required by the most
      efficient strain, AS96 (Shewanella putrefaciens) were as short as 4 h for
      complete decolorization of 100 mg l(-1) of AR-88 and DR-81 dyes under static
      conditions, and 6 and 8 h, respectively, for complete decolorization of RB-5 and
      DO-3. To our knowledge, these bacterial strains are the most efficient azo-dye
      degrading bacteria that have been described and may have practical application
      for biological treatment of dye-polluted wastewater streams.

PMID- 18084756
TI  - Properties and applications of microbial D-amino acid oxidases: current state and
      perspectives.
AB  - D: -Amino acid oxidase (DAAO) is a biotechnologically relevant enzyme that is
      used in a variety of applications. DAAO is a flavine adenine dinucleotide
      containing flavoenzyme that catalyzes the oxidative deamination of D-isomer of
      uncharged aliphatic, aromatic, and polar amino acids yielding the corresponding
      imino acid (which hydrolyzes spontaneously to the alpha-keto acid and ammonia)
      and hydrogen peroxide. This enzymatic activity is produced by few bacteria and by
      most eukaryotic organisms. In the past few years, DAAO from mammals has been the
      subject of a large number of investigations, becoming a model for the
      dehydrogenase-oxidase class of flavoproteins. However, DAAO from microorganisms
      show properties that render them more suitable for the biotechnological
      applications, such as a high level of protein expression (as native and
      recombinant protein), a high turnover number, and a tight binding of the
      coenzyme. Some important DAAO-producing microorganisms include Trigonopsis
      variabilis, Rhodotorula gracilis, and Fusarium solani. The aim of this paper is
      to provide an overview of the main biotechnological applications of DAAO (ranging
      from biocatalysis to convert cephalosporin C into 7-amino cephalosporanic acid to
      gene therapy for tumor treatment) and to illustrate the advantages of using the
      microbial DAAOs, employing both the native and the improved DAAO variants
      obtained by enzyme engineering.

PMID- 18084757
TI  - Myocardial imaging with 18F-fluoro-2-deoxyglucose positron emission tomography
      and magnetic resonance imaging in sarcoidosis.
AB  - PURPOSE: Despite accumulating reports on the clinical value of (18)F-fluoro-2
      deoxyglucose positron emission tomography (18F-FDG PET) and magnetic resonance
      imaging (MRI) in the assessment of cardiac sarcoidosis, no studies have
      systematically compared the images of these modalities. METHODS: Twenty-one
      consecutive patients with suspected cardiac sarcoidosis underwent cardiac
      examinations that included 18F-FDG PET and MRI. The association of 18F-FDG PET
      and MRI findings with blood sampling data such as serum angiotensin converting
      enzyme levels was also evaluated. RESULTS: Eight of 21 patients were diagnosed as
      having cardiac sarcoidosis according to the Japanese Ministry of Health and
      Welfare Guidelines for Diagnosing Cardiac Sarcoidosis. Sensitivity and
      specificity for diagnosing cardiac sarcoidosis were 87.5 and 38.5%, respectively,
      for 18F-FDG PET, and 75 and 76.9%, respectively, for MRI. When the 18F-FDG PET
      and MRI images were compared, 16 of 21 patients showed positive findings in one
      (n = 8) or both (n = 8) of the two modalities. In eight patients with positive
      findings on both images, the distribution of the findings differed among all
      eight cases. The presence of positive findings on 18F-FDG PET was associated with
      elevated serum angiotensin-converting enzyme levels; this association was not
      demonstrated on MRI. CONCLUSIONS: Both 18F-FDG PET and MRI provided high
      sensitivity for diagnosing cardiac sarcoidosis in patients with suspected cardiac
      involvement, but the specificity of (18)F-FDG PET was not as high as previously
      reported. The different distributions of the findings in the two modalities
      suggest the potential of 18F-FDG PET and MRI in detecting different pathological
      processes in the heart.

PMID- 18084758
TI  - An 8- to 10-year review of the Rotaglide total knee replacement.
AB  - Mobile-bearing knee arthroplasty (MBKA) is an alternative to fixed-bearing knee
      arthroplasty. This was a retrospective study of the Rotaglide Total Knee System.
      We present the results of the monitoring of 77 patients (85 knees) with a median
      duration to failure or end of follow up of 8.5 years (range 0.4 to 10.1 years).
      Patients were clinically and radiologically assessed at dedicated follow up
      clinics. The Hospital for Special Surgery (HSS) and Knee Society Score (KSS)
      systems were used to describe the clinical and radiological findings. The
      prosthesis had an estimated survival probability of 93.5% (standard error 3.4%)
      at 9 years. It is associated with good rates of patient satisfaction and high
      scores on the HSS and KSS systems. No knees were revised for aseptic loosening.
      This knee replacement has a survival rate equivalent to other prostheses. It is a
      safe and reliable prosthesis associated with good clinical outcome.

PMID- 18084759
TI  - Stress fractures presenting as tumours: a retrospective analysis of 22 cases.
AB  - Frequently, the imaging features of stress fractures may be misinterpreted as
      tumour-like lesions. The aim of this study was to analyse the quality of
      different examinations in detecting stress fractures mimicking tumour-like
      lesions in magnetic resonance imaging (MRI). We evaluated 22 cases which were
      referred to our department with the suspected diagnosis of bone tumours turning
      out to be stress fractures. Whenever the MRI did not lead to a diagnosis after a
      second review, computed tomography (CT) scans and, if still required, additional
      examinations were performed until the fracture was detected. A stress fracture
      was diagnosed in 15 cases after the additional CT scan, in five cases with the
      review of the MRI and in two cases with a combination of several examinations.
      Especially in stress fractures of the tibia and the femur, CT scanning was
      essential for making a diagnosis by detecting the fracture line. Bone scans and
      biopsies, in contrast, were not helpful in making a correct diagnosis.

PMID- 18084761
TI  - The expression levels of telomerase catalytic subunit hTERT and oncogenic MYC in
      essential thrombocythemia are affected by the molecular subtype.
AB  - The role of telomerase catalytic subunit hTERT in clonal malignancies including
      human leukemia is fundamental in overcoming cell senescence and enabling
      prolonged proliferation. One direct transcriptional activator of hTERT is the
      oncogene MYC which is known to be, in turn, activated by JAK2. To explore the
      relationship of telomerase, MYC and JAK2 in chronic myeloproliferative diseases,
      we investigated hTERT and MYC expression in bone marrow cells of essential
      thrombocythemia (ET) and polycythemia vera (PV). We could determine an up
      regulation of MYC expression exclusively in JAK2(wt) ET, whereas hTERT expression
      was rather inconsistent across the groups. Interestingly, a significant
      correlation between MYC and hTERT expression could only be established in
      homozygous JAK2(V617F) PV and control cases. Thus, the functional link between
      MYC and hTERT seems to be impaired depending on the molecular ET subtype, which
      in turn may have implications on the phenotype and course of the disease.

PMID- 18084760
TI  - Biochemical markers of bone turnover in aseptic loosening in hip arthroplasty.
AB  - The aim of this study was to determine the diagnostic value of systemic
      biochemical markers of bone turnover in aseptic loosening in hip arthroplasty,
      namely the urine levels of three bone resorption peptides - crosslinked n
      telopeptides (NTX), c-telopeptides (CTX I) and deoxypyridinoline (DPD). We
      compared 52 patients with surgically proven component loosening with 52 patients
      without clinical or radiological signs of endoprosthetic loosening and 52 healthy
      individuals. All three markers were measured using commercially available enzyme
      linked immunoassays. We found significantly increased levels of DPD in the
      loosening group (p < 0.05), but there was no significant difference between the
      loosening group and the two reference groups for the other two markers tested.
      Our data suggest that DPD can be used as an additional tool in the diagnosis of
      aseptic loosening in hip arthroplasty but CTX I and NTX have no predictive value
      in this context.

PMID- 18084762
TI  - Acute splenic sequestration crisis (ASSC) in an adult patient with beta
      thalassemia sickle cell disease: a life-threatening complication.

PMID- 18084763
TI  - Cisplatin, gemcitabine and treosulfan is effective in chemotherapy-pretreated
      relapsed stage IV uveal melanoma patients.
AB  - PURPOSE: The efficacy of cisplatin, gemcitabine, and treosulfan (CGT) was
      evaluated in patients with chemotherapy pretreated relapsed AJCC stage IV uveal
      malignant melanoma. METHODS: Patients received i.v./intrahepatic cisplatin, i.v.
      gemcitabine, and i.v. treosulfan (CGT) on day 1 and 8 as first-line (n = 1),
      second-line (n = 9), third-line (n = 1) or fourth-line (n = 1) therapy.
      Cisplatin, gemcitabine, and treosulfan (CGT)-therapy was repeated every 5 weeks
      until progression of disease occurred. A maximum of six CGT-cycles (mean, 2
      cycles) was administered per patient. RESULTS: No objective response was
      observed, six patients (50%) had stable disease and six (50%) patients progressed
      upon first reevaluation. Overall survival of all the 12 patients was 6 months.
      Patients with stable disease reached a median overall survival of 12 months,
      while patients with disease progression upon first reevaluation had a median
      overall survival of 4 months, only. Grade III/IV related hematotological side
      effects were experienced in six (leukopenia) and four (thrombocytopenia)
      patients. CONCLUSIONS: Treatment with CGT may lead to disease stabilization and
      prolonged survival in a substantial proportion of progressive stage IV uveal
      melanoma patients, even following heavy chemotherapy treatment.

PMID- 18084764
TI  - Pharmacokinetics of heated intraperitoneal oxaliplatin.
AB  - OBJECTIVE: To evaluate the pharmacokinetic inter-patient variability of 30-min
      hyperthermic intraperitoneal oxaliplatin chemotherapy. PATIENTS AND METHODS: Data
      were obtained from 24 patients who were treated according to two procedures of
      heated intra-operative intraperitoneal oxaliplatin. For the first procedure (12
      patients), the solution instilled within the peritoneal cavity contained
      oxaliplatin, and a delay of 8-10 min was necessary to reach a temperature of 42
      43 degrees C. For the second procedure (12 patients), the cavity was initially
      filled only with the dextrose solution, and oxaliplatin was added to the
      peritoneal instillate when temperature reached 42-43 degrees C. Plasma and
      peritoneal fluid oxaliplatin concentrations were analyzed according to a
      population pharmacokinetic approach using NONMEM. RESULTS: Peritoneal and total
      plasma data were simultaneously analyzed according to a three-compartment
      pharmacokinetic model. The peritoneal half-life ranged between 18 and 42 min. The
      mean peritoneal clearance was 5.47 L/h (+/-21%), and the mean plasma clearance
      was 3.71 L/h (+/-47%). The heated intra-operative procedure did not have any
      impact on oxaliplatin pharmacokinetics. CONCLUSION: The inter-individual
      variability was larger for plasma pharmacokinetic parameters than that for
      peritoneal parameters. However, the percentage of oxaliplatin dose absorbed
      during a 30-min hyperthermic intraperitoneal chemotherapy may vary from 40 to
      68%. The present pharmacokinetic model will be useful to implement
      pharmacokinetic evaluation of further clinical trials of hyperthermic
      intraperitoneal chemotherapy based on platinum compounds' administration.

PMID- 18084765
TI  - Maintaining phase of the crustacean tri-phasic pyloric rhythm.
AB  - We construct and analyze a model network of the pyloric rhythm of the crustacean
      stomatogastric ganglion consisting of an oscillator neuron that inhibits two
      reciprocally inhibitory follower neurons. We derive analytic expressions that
      determine the phase of firing of the follower neurons with respect to the
      oscillator. An important aspect of the model is the inclusion of synapses that
      exhibit short-term synaptic depression. We show that these type of synapses allow
      there to be a complicated relationship between the intrinsic properties of the
      neurons and the synapses between them in determining phase relationships. Our
      analysis reveals the circumstances and ranges of cycle periods under which these
      properties work in concert with or independently from one another. In particular,
      we show that phase maintenance over a range of oscillator periods can be enhanced
      through the interplay of the two follower neurons if the synapses between these
      neurons are depressing. Since our model represents the core of the oscillatory
      pyloric network, the results of our analysis can be compared to experimental data
      and used to make predictions about the biological network.

PMID- 18084767
TI  - Isolation and characterization of a molecule stimulatory to growth of somatic
      embryos from early stage female gametophyte tissue of loblolly pine.
AB  - Loblolly pine (LP, Pinus taeda) is the primary commercial species in southern
      forests of the US. Somatic embryogenesis (SE) is an effective technique to
      implement clonal tree production of high-value genotypes from breeding and
      genetic engineering programs. Unlike angiosperm embryos with attached cotyledons
      as seed storage organs, the diploid conifer embryo is surrounded by the
      unattached haploid female gametophyte (FG). The FG is not present in culture.
      This presents a dilemma if the FG produces necessary or regulatory compounds for
      embryo growth, since in culture these important compounds would be missing and
      would have to be added as supplements. We report here the direct evidence that
      extracts from early-stage FG indeed stimulate early-stage somatic embryo (SME)
      growth and multiplication, whereas extracts from late-stage FG inhibit early
      stage SME growth. Furthermore, we have now isolated this stimulatory substance
      from early-stage FG tissue, and identified this substance as citric acid on the
      basis of NMR and mass spectrometry. We then demonstrated that topical application
      of citric acid to SMEs stimulates embryo colony growth at P = 0.05. Moreover, we
      find that there is a good correlation between the amount of citric acid isolated
      from FG tissue (65 nmoles per stage 2-3 FG) and the amount of citric acid that
      stimulates colony growth (25-50 nmoles) when applied topically to SMEs. This
      approach of isolating and characterizing a molecule from plant tissue, and
      investigating its role on SE processes can provide valuable information leading
      to further applications of these molecules to improve LP SE protocols.

PMID- 18084766
TI  - Ethylene and shoot regeneration: hookless1 modulates de novo shoot organogenesis
      in Arabidopsis thaliana.
AB  - We have investigated the role of ethylene in shoot regeneration from cotyledon
      explants of Arabidopsis thaliana. We examined the ethylene sensitivity of five
      ecotypes representing both poor and prolific shoot regenerators and identified
      Dijon-G, a poor regenerator, as an ecotype with dramatically enhanced ethylene
      sensitivity. However, inhibiting ethylene action with silver nitrate generally
      reduced shoot organogenesis in ecotypes capable of regeneration. In ecotype Col
      0, we found that ethylene-insensitive mutants (etr1-1, ein2-1, ein4, ein7)
      exhibited reduced shoot regeneration rates, whereas constitutive ethylene
      response mutants (ctr1-1, ctr1-12) increased the proportion of explants producing
      shoots. Our experiments with ethylene over-production mutants (eto1, eto2 and
      eto3) indicate that the ethylene biosynthesis inhibitor gene, ETO1, can act as an
      inhibitor of shoot regeneration. Pharmacological elevation of ethylene levels was
      also found to significantly increase the proportion of explants regenerating
      shoots. We determined that the hookless1 (hls1-1) mutant, a suppressor of the
      ethylene response phenotypes of ctr1 and eto1 mutants, is capable of dramatically
      enhancing shoot organogenesis. The effects of ACC and loss of HLS1 function on
      shoot organogenesis were found to be largely additive.

PMID- 18084768
TI  - Volumetric high-frequency Doppler ultrasound enables the assessment of early
      antiangiogenic therapy effects on tumor xenografts in nude mice.
AB  - The sensitivity of Doppler ultrasound below 10 MHz to assess antiangiogenic
      therapy effects in tumor xenografts has been shown to be limited. Thus, our aim
      was to evaluate high-frequency volumetric power-Doppler ultrasound (HF-VPDU) for
      monitoring antiangiogenic treatments. Squamous cell carcinoma xenografts grown in
      nude mice were scanned with HF-VPDU at a center frequency of 30 MHz. Images with
      200-microm slice thicknesses were recorded and merged into a three-dimensional
      dataset, of which the relative color pixel density was determined. Animals
      received either VEGFR2 antibodies or 0.9% NaCl and were examined at days 0, 3 and
      6 of treatment. After the last examination, tumors were resected and their
      vascularization characterized by immunohistology. At day 6, the volumes of
      treated and untreated tumors were not significantly different yet. In contrast,
      mean tumor vascularization in treated animals had decreased to 44%, while in the
      control group it had increased to 152% (P < 0.01). In correspondence, vessel
      density, as determined by CD31 staining, was 0.19 +/- 0.10% in treated and 0.92
      +/- 0.41% in untreated tumors (P < 0.01). Additionally, the fraction of mature
      (SMA-positive) vessels increased under therapy. Thus, HF-VPDU can be considered
      as an easily applicable and fast method to screen high animal numbers for
      antiangiogenic therapy effects.

PMID- 18084769
TI  - Urea loading enhances postfreeze performance of frog skeletal muscle.
AB  - The wood frog (Rana sylvatica) is a terrestrial hibernator that can accumulate
      urea as an osmoprotectant in autumn and winter. This study tested the hypothesis
      that elevated urea can also function as a cryoprotectant in this freeze-tolerant
      species. Performance characteristics (threshold stimulus voltage, maximal
      isometric twitch and tetanic contraction forces, and (1/2) fatigue time) of
      isolated gastrocnemius muscles were measured before and after experimental
      freezing at -1.5 degrees C for 18 h, followed by thawing. Frozen/thawed muscles
      exhibited reduced function relative to baseline (prefreeze) levels; however,
      muscles preincubated in a saline solution containing urea (80 mmol l(-1))
      performed substantially better in some tests than muscles incubated without urea.
      Concentrations of urea in these treated muscles, approximately 65 mmol l(-1),
      were within the physiological range in winter R. sylvatica. Reducing tissue urea
      levels to approximately 33 mmol l(-1) resulted in a similar pattern of response,
      although the differences between urea-incubated and saline-incubated muscles were
      not statistically significant. Tests of cryoprotective efficacy were also
      performed on gastrocnemius muscles from R. pipiens, a closely related, but freeze
      intolerant species that hibernates aquatically and thus has little need to
      accumulate urea. Urea-treated muscles from this species performed no better than
      muscles incubated in saline, attesting that freeze tolerance cannot be conferred
      simply by augmenting cryoprotectant levels. Overall, these results bolster an
      earlier report that urea accumulated in response to low moisture availability can
      serve a cryoprotective role in freeze-tolerant ectotherms.

PMID- 18084770
TI  - Focal nodular hyperplasia in biliary atresia patient after Kasai hepatic
      portoenterostomy.
AB  - We present the case of a 10-year-old girl with biliary atresia in whom focal
      nodular hyperplasia (FNH) of the liver occurred following successful "Kasai"
      hepatic portoenterostomy at the age of 2 months. Her jaundice completely
      disappeared a few weeks after the operation. A 4-cm diameter liver tumor in
      segment IV was found when she was 5-years old. Needle biopsy could not establish
      a definitive diagnosis. Because the tumor size was not changing, she was
      conservatively followed by abdominal echo at an outpatient clinic. She showed
      progressive liver dysfunction and ongoing cirrhosis, and so at the age of 10
      years, she received living donor liver transplantation at our institute. The
      tumor was pathologically diagnosed as a FNH. Though a FNH in biliary atresia
      patients is extremely rare, there are only two cases reported in the literature;
      it should be considered in the differential diagnosis for a hepatic nodule during
      a long follow-up course in patients with biliary atresia.

PMID- 18084771
TI  - Gracilis transposition for repair of recurrent anovaginal and rectovaginal
      fistulas in Crohn's disease.
AB  - OBJECTIVE: Local surgical procedures in the presence of Crohn's disease have a
      markedly reduced success rate, especially in the treatment of recurrent
      anovaginal and distant rectovaginal fistulas. In these patients, local surgery
      (e.g., flap closure) has unsatisfactory results if the anal canal is destroyed by
      ulceration and indurations or in patients with extensive defects of the perineum.
      MATERIALS AND METHODS: Over a period of 6 years (2000 to 2006), 12 patients with
      recurrent rectovaginal fistulas were treated with graciloplasty. The age of the
      female patients ranged from 24 to 47 years, the mean age being 38 years. The
      presence of Crohn's disease in all patients had a mean duration of 12 years.
      Corticosteroids, mesalazin, or azathioprin were administered preoperatively. All
      patients were diverted by a temporary ileostomy before graciloplasty. RESULTS
      Rectovaginal fistula was closed in 11 of 12 patients after graciloplasty with a
      mean follow-up of 3.4 years. One rerecurrence of a rectovaginal fistula was
      documented. One of 12 ileostomies was not closed due to persistence of the
      fistula tract. One patient had a pouch-anal and, additionally, a pouch-vaginal
      fistula. In this patient, the first transposition of the gracilis muscle was
      unsuccessful. After a few months, she underwent renewed graciloplasty. There was
      no recurrence of a fistula within the follow-up period. Reconstruction of the
      perineum constituted an additional positive effect of the graciloplasty. In one
      patient, the preexisting fecal incontinence persisted, even after secondary
      implantation of a pacemaker. Due to diarrhea and persistent fecal incontinence,
      the patient opted for a renewed ileostomy. CONCLUSIONS: In our series, gracilis
      transposition in the treatment of recurrent anovaginal and rectovaginal fistulas
      in patients with Crohn's disease has excellent short-term results. In addition,
      graciloplasty can reconstruct the perineal defect.

PMID- 18084772
TI  - Calcaneal nonunion: three cases and a review of the literature.
AB  - The long-term follow-up of intra-articular calcaneal fractures is often
      accompanied by complications. Frequently occurring are arthrosis, arthrofibrosis
      of the subtalar joint, and malunion. Uncommon is the calcaneal nonunion. A total
      of three cases is presented in this report, including a review of the literature.
      The occurrence of a nonunion appears to be more common after conservative
      treatment, but the pathophysiology remains unclear, however smoking may play a
      role.

PMID- 18084773
TI  - Expression of PTPIP51 during mouse eye development.
AB  - The expression pattern of the novel tyrosine phosphatase interacting protein 51
      (PTPIP51) was studied during the organogenesis of mouse eye on a transcriptional
      (RT-PCR and in situ hybridization) and translational level (immunohistochemistry
      and immunoblotting). Timed developmental stages from day E12 to day E18 were
      analyzed regarding the distribution of PTPIP51 and compared to the expression
      patterns observed during postnatal developmental stages and adult eye. PTPIP51
      was found to be expressed in all investigated developmental stages in derivatives
      of mesoderm and ectoderm, such as developing cornea, lens, neuroretina and
      extraocular muscles. Conjuctiva and corneal epithelia were PTPIP51 reactive
      during all investigated developmental stages including the mature eye. Embryonic
      differentiation led to reactive keratocytes of the corneal stroma and remained so
      in post partal stages, as well as in the adult eye. On day E12, all cells
      comprising the developing lens body showed PTPIP51 expression. Further
      development unto the adult eye resulted in a restriction of PTPIP51 expression to
      the anterior lens epithelium and finally to the equatorial region of the lens
      epithelium. The developing neuroretina showed a strong PTPIP51 expression in the
      inner neuroblastic layer and the future receptor cell layer. In the adult eye,
      the retinal ganglion cells and the inner nuclear layer remained PTPIP51 reactive.
      The data presented here suggests PTPIP51 to be integrated in signaling cascades
      regulating differentiation and apoptosis during eye development.

PMID- 18084775
TI  - Non-evaporative effects of a wet mid layer on heat transfer through protective
      clothing.
AB  - In order to assess the non-evaporative components of the reduced thermal
      insulation of wet clothing, experiments were performed with a manikin and with
      human subjects in which two layers of underwear separated by an impermeable
      barrier were worn under an impermeable overgarment at 20 degrees C, 80% RH and
      0.5 ms(-1) air velocity. By comparing manikin measurements with dry and wetted
      mid underwear layer, the increase in heat loss caused by a wet layer kept away
      from the skin was determined, which turned out to be small (5-6 W m(-2)),
      irrespective of the inner underwear layer being dry or wetted, and was only one
      third of the evaporative heat loss calculated from weight change, i.e.
      evaporative cooling efficiency was far below unity. In the experiments with eight
      males, each subject participated in two sessions with the mid underwear layer
      either dry or wetted, where they stood still for the first 30 min and then
      performed treadmill work for 60 min. Reduced heat strain due to lower insulation
      with the wetted mid layer was observed with decreased microclimate and skin
      temperatures, lowered sweat loss and cardiac strain. Accordingly, total clothing
      insulation calculated over the walking period from heat balance equations was
      reduced by 0.02 m(2) degrees C W(-1) (16%), while for the standing period the
      same decrease in insulation, representing 9% reduction only showed up after
      allowing for the lower evaporative cooling efficiency in the calculations. As
      evaporation to the environment and inside the clothing was restricted, the
      observed small alterations may be attributed to the wet mid layer's increased
      conductivity, which, however, appears to be of minor importance compared to the
      evaporative effects in the assessment of the thermal properties of wet clothing.

PMID- 18084774
TI  - Role of muscle mass on sprint performance: gender differences?
AB  - The aim of this study was to determine if gender differences in muscle mass
      explain the gender differences in running and cycling sprint performance. Body
      composition (dual-energy X-ray absorptiometry), and running (30 and 300 m test)
      and cycling (Wingate test) sprint performance were assessed in 123 men and 32
      women. Peak power (PP) output in the Wingate test expressed per kg of lower
      extremities lean mass (LM) was similar in males and females (50.4 +/- 5.6 and
      50.5 +/- 6.2 W kg(-1), P = 0.88). No gender differences were observed in the
      slope of the linear relation between LM and PP or mean power output (MP).
      However, when MP was expressed per kg of LM, the males attained a 22% higher
      value (26.6 +/- 3.4 and 21.9 +/- 3.2 W kg(-1), P < 0.001). The 30 and 300-m
      running time divided by the relative lean mass of the lower extremities (RLM = LM
      x 100/body mass) was significantly lower in males than in females. Although, the
      slope of the linear relationship between RLM and 300-m running time was not
      significantly different between genders, the males achieved better performance in
      the 300-m test than the females. The main factor accounting for gender
      differences in peak and mean power output during cycling is the muscle mass of
      the lower extremities. Although, the peak power generating capability of the
      muscle is similar in males and females, muscle mass only partially explains the
      gender difference in running sprints, even when expressed as a percentage of the
      whole body mass.

PMID- 18084776
TI  - LAMA4, highly expressed in human hepatocellular carcinoma from Chinese patients,
      is a novel marker of tumor invasion and metastasis.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common malignant
      tumors in China. Hepatocarcinogenesis is correlated with a series of gene
      expression alteration. Here, we investigated LAMA4 gene expression in
      hepatocellular carcinoma on both mRNA and protein levels, expecting to explore
      the relationship between expressional abundances of LAMA4 and the clinical
      characteristics of HCC specimens. METHOD: Total RNA was extracted from 48 cases
      of surgically resected HCC specimens and their corresponding peripheral tumor
      free liver tissues. After the optimal reverse transcription polymerase chain
      reaction condition was established, the mRNA levels of LAMA4 in tumor and
      peripheral tumor-free tissues were examined semi-quantitatively. The relationship
      between expression levels of LAMA4 and clinical pathological characteristics was
      further analyzed by two-tailed t-test and chi2 test. We also used anti-LAMA4
      antibody to detect the in vivo distribution of LAMA4 protein by tissue
      immunofluorescence staining in HCC specimens and their peripheral tumor-free
      tissues. RESULTS: The expression level of LAMA4 in 48 cases of human
      hepatocellular carcinoma tissues was significantly higher than that in their
      corresponding peripheral tumor-free tissues (0.37 +/- 0.25 vs. 0.18 +/- 0.12, P <
      0.01). LAMA4 gene was up-regulated in 30 (62.50%) cases of HCC, down regulated in
      4 (8.33%) cases, and showed no significant changes in 14 (29.17%) cases. Analysis
      of relationship between LAMA4 gene expression abundances and clinical
      characteristics by chi2 test showed that up-regulation of LAMA4 was strongly
      correlated with tumor invasion (79.31%), incomplete or no envelope (75.00%) and
      tumor bolt (86.67%). Additionally, tissue immunofluorescence staining against
      LAMA4 protein detected strong signal only in HCC tissues but not their
      corresponding peripheral tumor-free liver tissues. To our attention, LAMA4
      protein showed specific in vivo distribution along the basement membrane of tumor
      blood vessels, bringing insights into its potential role in tumor angiogenesis.
      CONCLUSIONS: LAMA4 is specifically up-regulated on both mRNA and protein levels
      in hepatocelluar carcinoma. The strong correlation between high expression
      abundances of LAMA4 with tumor invasion and metastasis, as well as, LAMA4
      specific in vivo distribution in tumor basement membrane, indicated LAMA4's
      potential role in hepatocarcinogenesis and tumor progression. Therefore, we
      hypothesize that LAMA4 is probably a novel supplementary marker for HCC
      diagnosis, and might be a molecular target in the future cancer therapy.

PMID- 18084777
TI  - Sarcocystis sp. from the goldeneye (Bucephala clangula) and the mallard (Anas
      platyrhynchos): cyst morphology and ribosomal DNA analysis.
AB  - By light microscopy, cysts of Sarcocystis sp. (cyst type I) from the goldeneye
      (Bucephala clangula) seemed filamentous with a smooth and thin (<1 microm) cyst
      wall. Ultrastructurally, the cyst wall surface was irregular with minute
      undulations of the primary cyst wall. These sarcocysts had type-1 cyst wall.
      Cystozoites were banana-shaped and measured 7.0-8.5 microm in length. By light
      microscopy, cysts of Sarcocystis sp. (cyst type II) from the mallard (Anas
      platyrhynchos) were ribbon-shaped, very long, and thin. On the surface of the
      wall (up to 1.5 microm), they had palisade-like villar protrusions closely
      crowded together. Electron micrographs showed villar protrusions (up to 1.3
      microm in length) different in size and shape. The latter had short
      microprojections especially obvious in the oblique sections. Cystozoites were
      slightly bent with blunt ends, broader at one end, and measured 13.0-16.1 x 1.8
      2.5 microm. Phylogenetic analysis based on the comparison of partial 28S rRNR
      gene sequences of Sarcocystis sp. (cyst type II) derived from the mallard,
      Sarcocystis sp. (cyst type I) and Sarcocystis sp. (cyst type III) both derived
      from the white-fronted goose (Anser albifrons) suggested that these sequences
      belonged to separate Sarcocystis species.

PMID- 18084779
TI  - Alternative camouflage strategies mediate predation risk among closely related co
      occurring kelp crabs.
AB  - Although camouflage is a common predator defense strategy across a wide variety
      of organisms, direct tests of the adaptive and ecological consequences of
      camouflage are rare. In this study, we demonstrated that closely related crabs in
      the family Epialtidae coexist in the same algal environment but use alternative
      forms of camouflage--decoration and color change--to protect themselves from
      predation. Decoration and color change are both plastic camouflage strategies in
      that they can be changed to match different habitats: decoration occurs on a
      short timescale (hours to days), while color change accompanies molting and
      occurs on longer timescales (months). We found that the species that decorated
      the most had the lowest magnitude of color change (Pugettia richii); the species
      that decorated the least showed the highest magnitude of color change (Pugettia
      producta), and a third species (Mimulus foliatus) was intermediate in both
      decoration and color change, suggesting a negative correlation in utilization of
      these strategies. This negative correlation between color change and decoration
      camouflage utilization mirrored the effectiveness of these camouflage strategies
      in reducing predation in different species. Color camouflage primarily reduced
      predation on P. producta, while decoration camouflage (but not color camouflage)
      reduced predation on P. richii. These results indicate there might be among
      species trade-offs in utilization and/or effectiveness of these two forms of
      plastic camouflage, with important consequences for distribution of these species
      among habitats and the evolution of different camouflage strategies in this
      group.

PMID- 18084778
TI  - Conidiation rhythm and light entrainment in superoxide dismutase mutant in
      Neurospora crassa.
AB  - Conidial formation in the filamentous fungus Neurospora crassa is regulated by
      nutritional conditions, light, and the circadian clock. We found that a sod-1
      mutant, with a defective superoxide dismutase catalyzing the conversion of
      superoxide to hydrogen peroxide, had a slightly shorter period length than the
      wild type and clear conidial banding similar to a mutant of band (bd). However,
      unlike the bd mutant, the sod-1 mutant could sustain conidial banding with light
      pulses on a nutrient-rich medium, which involved an enhancement of the light
      induced transcription of frequency (frq). sod-1 was hypersensitive to entrainment
      of the conidiation rhythm by light in race tubes. Furthermore, a frq(10); sod-1
      double mutant showed conidiation rhythm in darkness and could be synchronized to
      light/dark cycles by the masking effect of light. These genetic analyses
      suggested that intracellular reactive oxygen species (ROS) act on circadian
      conidiation via multiple circadian clocks and output pathways.

PMID- 18084780
TI  - Modeling synchronous growth of bacterial populations in phased cultivation.
AB  - The phasing technique is a method for synchronizing cell populations in a
      bioreactor. Periodic changes of substrate supply and depletion can provoke a cell
      cycle phasing of originally stochastic scattered proliferation patterns.
      Synchronized cell populations characterized by changes in DNA content
      distribution can be monitored by flow cytometry. Thus, studies of the dynamics of
      single cells in specific cell cycle phases are facilitated. Here we present an
      age structured model framework investigating synchronized populations using delay
      differential equations. Applying the framework not only cell populations
      synchronously increasing under balanced growth conditions, but also synchronized
      cultures growing in continuous phasing experiments can be described. A process
      model developed for describing phased cultures was fitted to growth data obtained
      from a synchronous cultivation of Cupriavidus necator. Its potential utility is
      demonstrated by a quantitative process description and by its ability to identify
      ways in which the grade of synchrony could be improved.

PMID- 18084781
TI  - [Patients with versus without psychological disorders in orthopedic
      rehabilitation].
AB  - BACKGROUND: In this study it was examined whether orthopedic rehabilitants with
      versus without a comorbid mental disorder profit from inpatient orthopedic
      rehabilitation to the same degree. It was also investigated whether there were
      differential treatment effects between the traditional and behavioral-medical
      rehabilitation approaches. METHOD: Questionnaires which assess pain-specific and
      associated variables were issued to a total of 361 patients on admission and
      discharge from rehabilitation. RESULTS: In some aspects patients with a mental
      disorder benefited more from the treatment than patients without comorbidities.
      Differential treatment effects were found only in patients with a mental disorder
      and improvements were higher in the behavioral-medical than in the traditional
      rehabilitation approaches. CONCLUSION: Psychological interventions in the
      inpatient orthopedic rehabilitation are recommended in order to adequately deal
      with the higher rate of persons with comorbid mental disorders.

PMID- 18084782
TI  - Predictive factors for long-term outcome of anterior cervical decompression and
      fusion: a multivariate data analysis.
AB  - We conducted a prospective randomized study to investigate predictive factors for
      short- and long-term outcome of anterior cervical decompression and fusion (ACDF)
      as measured by current pain intensity on the Visual Analogue Scale (VAS) and by
      disability using the Neck Disability Index (NDI). Current understanding about how
      preoperative and short-term outcome data predict long-term outcome is sparse, and
      there are few studies involving analysis of short-term follow-up using
      multivariate approaches with quantification of the relative importance of each
      variable studied. A total of 95 patients were randomly allocated for ACDF with
      the cervical intervertebral fusion cage or the Cloward procedure. The mean follow
      up time was 19 months (range 12-24) for short-term follow-up and 76 months (range
      56-94 months) for long-term. Background factors, radiologically detected
      findings, physiological measurements, treatment type, pain, and disability were
      used as potential predictors. Multivariate statistical analysis by projection to
      latent structures was used to investigate predictors of importance for short- and
      long-term outcome of ACDF. A "preoperative" low disability and pain intensity,
      non-smoking status, male sex, good hand strength, and an active range of motion
      (AROM) in the neck were significant predictors for good short- and long-term
      outcomes. The short-term outcome data were better at predicting long-term outcome
      than were baseline data. Radiologically detected findings and surgical technique
      used were mainly insignificant as predictors. We suggest that the inclusion
      criteria for ACDF should be based on a bio-psycho-social model including NDI. NDI
      may also be regarded as an important outcome measurement in evaluation of ACDF.

PMID- 18084783
TI  - Direct microwave transesterification of fingertip prick blood samples for fatty
      acid determinations.
AB  - Omega-3 polyunsaturated fatty acid (PUFA) dietary intakes and tissue levels are
      positively associated with various health benefits. The development of cost
      efficient, high throughput methodologies would enable research in large clinical
      and population studies, and clinical fatty acid profiling. Microwave heating for
      the transesterification of blood fatty acids was examined. Samples were collected
      by venous puncture and fingertip prick onto chromatography paper. Aliquots of
      serum, plasma, erythrocytes and whole blood were prepared from venous blood.
      Boron trifluoride in methanol was used for transesterification but sample
      preparation and heating varied. Fatty acid determinations and markers of omega-3
      fatty acid status including the sum of eicosapentaenoic acid and docosahexaenoic
      acid, the ratio of total n-3 PUFA to n-6 PUFA, and the percentage of n-3 highly
      unsaturated fatty acids (HUFA, >or=20 carbons and >or=3 carbon-carbon double
      bonds) in total HUFA were compared. Quantitative determinations indicate that
      microwave transesterification results in significantly lower estimates of
      monounsaturates and polyunsaturates, possibly through incomplete
      transesterification of triacylglycerols. However, qualitative estimates of omega
      3 fatty acid status were relatively similar. Fingertip prick blood collection
      combined with direct transesterification by microwave may be a very rapid method
      to estimate omega-3 fatty acid status for selected applications.

PMID- 18084784
TI  - Validation of a rapid measure of blood PUFA levels in humans.
AB  - An assay involving a finger stick and filter paper blood spotting was developed
      to determine polyunsaturated fatty acid (PUFA) levels in blood. Capillary whole
      blood from a finger stick was blotted on antioxidant impregnated filter paper,
      air dried, saponified and methylated using sodium hydroxide and boron trifluoride
      in methanol. The method differed from those described previously because
      separation of plasma and red blood cells (RBCs) was not needed, thin-layer
      chromatography (TLC) was not required to separate phospholipids, initial
      extraction of lipids before transesterification was not necessary, and the fatty
      acid methyl ester (FAME) method was able to methylate steryl esters, free fatty
      acids, and sphingomyelins. Twenty-six subjects provided blood samples by finger
      stick and venipuncture. Levels of long-chain polyunsaturated fatty acids (LC
      PUFA) from capillary whole blood were correlated with those from RBCs and PLs in
      venous blood (P < 0.001, R(2) ranged from 0.64 to 0.86). Although highly
      significant (P < 0.002), the R(2) values for the correlation between arachidonic
      acid (ARA) levels in capillary whole blood with ARA levels in RBCs and plasma
      phospholipids (PLs) were relatively lower (R(2) = 0.31-0.41, respectively).
      Results indicate that the described finger stick assay represents a fast,
      reliable method to measure specific LC-PUFA levels.

PMID- 18084785
TI  - Identification and characterization of hamster stearoyl-CoA desaturase isoforms.
AB  - Stearoyl-CoA desaturase (SCD) catalyzes the formation of monounsaturated fatty
      acids from saturated fatty acids. It plays a key role in lipid metabolism and
      energy expenditure in mammals. In mice, four SCD isoforms (SCD1-4) have been
      identified. Here we report the identification of cDNA sequences corresponding to
      SCD1, SCD2 and SCD3 of golden hamster. The deduced amino acid sequences of these
      hamster SCD (hmSCD) isoforms display a high degree of homologies to their mouse
      counterparts (mouse SCD). Polyclonal antibodies specific to rodent SCDs detected
      proteins of predicted size in the human embryonic kidney 293 cells transfected
      with hmSCD cDNAs. Microsome fractions prepared from these cells also displayed
      increased SCD activity versus cells transfected with vector alone. Real-time
      reverse transcription-polymerase chain reaction analysis revealed the highest
      expression of hmSCD1 in liver and adipose tissue, while the highest hmSCD2
      expression was detected in the brain. Very low levels of hmSCD3 mRNA can be
      detected in the tissues tested. This report is the first description of three SCD
      isoforms in the hamster and will provide useful tools in the further study of
      fatty acids metabolism in this species.

PMID- 18084786
TI  - Primary hypercholesterolemia, carotid atherosclerosis and insulin resistance
      among Chinese.
AB  - We investigated the genetic contributions to carotid atherosclerosis and insulin
      resistance in Chinese patients with primary hypercholesterolemia. A family study
      of probands from the outpatient clinics in patients with high low-density
      lipoprotein cholesterol levels was conducted. A total of 62 families (360
      subjects) underwent carotid ultrasonography and insulin resistance measurement.
      The correlation coefficients of carotid intima-media thickness (IMT) were high
      among spouse, parent-offspring, and sibling pairs (0.39, 0.38 and 0.35,
      respectively). All insulin indices and IMT had significant estimates of
      heritability, of which fasting insulin had the highest heritability (0.410 +/-
      0.104, P = 0.0001), followed by homeostasis model assessment (HOMA) (0.395 +/-
      0.108, P = 0.0001). The estimated heritability of IMT was significant (0.185 +/-
      0.103, P = 0.025) but not of plaque score. Bivariate genetic coefficient between
      IMT and HOMA was 0.569 +/- 0.292, while the environmental coefficient was 0.028
      +/- 0.103. The study confirms a relationship between insulin resistance and
      atherosclerosis and, in particular, between insulin resistance and the thickening
      of the arterial wall. Moreover, it shows that genetics influence both insulin
      resistance and atherosclerosis, implying that the management of insulin
      resistance may benefit the prevention of atherosclerotic disease in familial
      hypercholesterolemia.

PMID- 18084787
TI  - Altered lipid response in hamsters fed cis-9,trans-11+trans-8,cis-10 conjugated
      linoleic acid mixture.
AB  - The objective of the present study was to compare the effects of cis-9,trans-11 +
      trans-8,cis-10 conjugated linoleic acid (CLA) mixture to those of cis-9,trans-11
      + trans-10,cis-12 CLA mixture and linoleic acid (LA) on lipoprotein profile,
      hepatic lipids, body composition and digestibility of dietary fat in hamsters (n
      = 17) fed diets containing 2% of experimental fat (w/w) for 28 days. The cis
      9,trans-11 + trans-10,cis-12 CLA mixture showed higher LDL cholesterol
      concentrations than LA and the cis-9,trans-11 + trans-8,cis-10 CLA mixture. The
      cis-9,trans-11 + trans-8,cis-10 CLA mixture induced similar plasma LDL
      cholesterol and hepatic lipid concentrations, and coefficient of digestibility as
      LA, indicating no effect of the trans-8,cis-10 CLA isomer on these lipid
      parameters. On the other hand, the cis-9,trans-11 + trans-8,cis-10 CLA mixture
      induced higher plasma VLDL cholesterol and triglycerides than LA and the cis
      9,trans-11 + trans-10,cis-12 CLA mixture. The cis-9,trans-11 + trans-8,cis-10 CLA
      mixture also induced the highest plasma glucose concentrations compared with the
      two other groups, indicating an impairment of glycemic control. No differences in
      body composition were noted between the three groups. The present results thus
      show that the cis-9,trans-11 + trans-8,cis-10 CLA mixture can deteriorate plasma
      VLDL cholesterol and triglycerides in hamsters, possibly due to an increased flux
      of glucose.

PMID- 18084788
TI  - Capturing proteins that bind polyunsaturated fatty acids: demonstration using
      arachidonic acid and eicosanoids.
AB  - Polyunsaturated fatty acids (PUFA) and their biological derivatives, including
      the eicosanoids, have numerous roles in physiology and pathology. Although some
      eicosanoids are known to act through receptors, the molecular actions of many
      PUFA remain obscure. As the three-dimensional structure of eicosanoids allows
      them to specifically bind and activate their receptors, we hypothesized that the
      same structure would allow other proteins to associate with PUFA and eicosanoids.
      Here, we demonstrate that biotinylation of arachidonic acid and its oxygenated
      derivatives 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene (LT) B(4) can
      be used to pull down associated proteins. Separation of proteins by two
      dimensional gel electrophoresis indicated that a large number of proteins bound
      each lipid and that proteins could distinguish between two enantiomers of 5-HETE.
      Individual proteins, identified by matrix assisted laser desorption/ionization
      time of flight mass spectrometry, included proteins that are known to bind
      lipids, including albumin and phosphatidylethanolamine-binding protein, as well
      as several novel proteins. These include cytoskeletal proteins, such as actin,
      moesin, stathmin and coactosin-like protein, and G protein signaling proteins,
      such as Rho GDP dissociation inhibitor 1 and nucleoside diphosphate kinase B.
      This method, then, represents a relatively simple and straightforward way to
      screen for proteins that directly associate with, and are potentially modulated
      by, PUFA and their derivatives.

PMID- 18084789
TI  - High-throughput analysis of plasma fatty acid methyl esters employing robotic
      transesterification and fast gas chromatography.
AB  - Fatty acid analysis is an important research tool, and indices derived from
      essential fatty acid contents serve as useful biomarkers related to
      cardiovascular and other chronic disease risk. Both clinical and basic studies of
      essential fatty acid composition are becoming ever larger in magnitude leading to
      delays while the rather laborious lipid analyses are performed. A robotic
      transesterification procedure has been developed for high-throughput analysis of
      plasma fatty acid methyl esters. In this approach, robots perform most steps
      including plasma and reagent transfer, transesterification reaction via heating
      at 80 degrees C in open tubes with multiple reagent additions, followed by two
      phase extraction and transfer of lipid extracts to GC vials. The vials are then
      placed directly onto a GC autosampler carousel for robotic sample injection. An
      improved fast GC method is presented in which the peaks of interest are eluted
      within 6 min. This method is readily scalable to prepare and analyze 200 samples
      per day (1,000 samples per week) so that large clinical trials can be
      accommodated.

PMID- 18084790
TI  - Efficacy of St. John's wort extract WS 5570 in acute treatment of mild
      depression: a reanalysis of data from controlled clinical trials.
AB  - Based on the original data from two double-blind, randomized, placebo-controlled
      clinical trials and the acute phase of a long-term study that investigated the
      antidepressant efficacy of St. John's wort extract WS 5570, we present a re
      analysis of a subset of patients suffering from an acute episode of mild
      depression according to DSM criteria. Out of a total of more than 1,200 patients
      included into these trials 217 had a pre-treatment total score < or =20 points on
      the 17-item Hamilton Rating Scale for Depression (HAMD) and were eligible for our
      re-analysis. They received 600, 900, or 1,200 mg/day WS 5570 or placebo for 6
      weeks. In patients treated with WS 5570 the HAMD total score decreased by
      averages of 10.8 (600 mg/day), 9.6 (900 mg/day), and 10.7 (1,200 mg/day) points
      between the pre-treatment baseline value and the end of acute treatment, compared
      to 6.8 points in the placebo group (p < 0.01 for all pairwise comparisons of WS
      5570 against placebo). This corresponded to average relative decreases by 49-57%
      for WS 5570 and by 36% for placebo. The rates of responders (i.e., patients with
      a HAMD total score decrease > or =50%) were 73%, 64%, 71%, and 37% for WS 5570
      600 mg/day, 900 mg/day and 1,200 mg/day, and placebo, respectively. At the end of
      acute treatment 57% of the patients treated with WS 5570 600 mg/day, 33% in the
      900 mg/day group and 62% in the 1,200 mg/day group, as well as 25% in the placebo
      group were in remission (HAMD total score < or =7 points). The analysis shows
      that St. John's wort extract WS 5570 has a meaningful beneficial effect during
      acute treatment of patients suffering from mild depression and leads to a
      substantial increase in the probability of remission.

PMID- 18084791
TI  - Qualitative changes in symptomatology as an effect of treatment with escitalopram
      in generalized anxiety disorder and major depressive disorder.
AB  - The purpose of this article is to examine the similarities and differences
      between patients with Major Depressive Disorder (MDD) versus Generalized Anxiety
      Disorder (GAD) versus MDD with anxiety symptoms. Data were analysed from all
      randomized double-blind clinical studies with escitalopram that measured symptoms
      using either Hamilton Anxiety Scale (HAMA) or Montgomery-Asberg Depression Rating
      Scale (MADRS). The contribution of each item of a scale to the total score was
      calculated before and after treatment, in remitters. Most single items of the
      HAMA contribute nearly equally in patients with GAD. In patients with MDD, four
      symptoms (i.e. anxious mood, tension, insomnia and concentration) contribute to
      most to the HAMA total score. In patients with GAD, three symptoms (tension,
      sleep and concentration) contribute two-thirds of the MADRS total score. In
      contrast, most MADRS items contribute equally to the total score in patients with
      MDD. After treatment to remission, the profile of residual symptoms MDD or GAD
      was similar to the symptom profile before treatment. Anxiety symptoms are very
      common in patients with MDD or GAD, and the symptomatic pattern is similar. In
      both disorders, the symptomatic pattern of residual symptoms is similar to the
      pattern of symptoms before treatment.

PMID- 18084794
TI  - [Invasive electrophysiology: complications, nightmares and their management].
AB  - Most minor side effects of ablation in the right atrium and right ventricle
      relate to femoral venous catheterization but there is a small risk of severe
      complications including atrioventricular (AV) block, damage of surrounding
      structures and thromboembolic events. Impairment of AV conduction can occur
      during ablation of atrioventricular re-entrant tachycardia, ablation of
      anteroseptal, mid-septal and parahisian accessory pathways, ablation of ectopic
      atrial tachycardia originating from the vicinity of the atrioventricular node and
      when ablating the septal isthmus for typical atrial flutter. Damage of the right
      coronary artery is a very rare complication after inferior isthmus ablation with
      high energy. The thromboembolic risk during and after cardioversion and ablation
      of atrial flutter is higher than previously recognized and anticoagulation
      therapy decreases this risk. The risk of perforation and tamponade during
      ablation in the right atrium and right ventricle is very low but particular
      caution is necessary in thin-walled structures such as the coronary sinus and the
      upper right ventricular outflow tract. Phrenic nerve injury can be avoided by
      pacing from the mapping electrode before application of radiofrequency energy at
      the right atrial free wall. Limitation of power output depending on the site of
      ablation and titration of energy application with continuous control of
      temperature and impedance should be considered to minimize the risk of
      complications.

PMID- 18084795
TI  - [Nightmares in atrial fibrillation ablation--identification, management, and
      prevention of complications in radiofrequency ablation of atrial fibrillation].
AB  - Radiofrequency ablation is increasingly being established as a curative treatment
      option for atrial fibrillation refractory to antiarrhythmic drug therapy.
      Especially catheter ablation of atrial fibrillation is associated with
      significant procedure-related risks, as this is one of the most complex
      interventional electrophysiologic procedures. Knowledge about common and
      infrequent complications, incidence, etiology, and techniques for prevention
      should minimize risk and help to further increase procedural success. This paper
      intends to provide a practice-oriented summary of international surveys and
      consensus documents in comparison with data from our own electrophysiologic
      laboratory. Great attention will be laid upon early recognition and technical as
      well as procedure-related possibilities to prevent any complication.

PMID- 18084796
TI  - Ablation of ventricular tachycardia.
AB  - Ablation is an important management tool for the treatment of ventricular
      arrhythmias. Even at experienced centers ventricular tachycardia ablation carries
      a minor but significant risk for potential complications, including vascular and
      thromboembolic complications, air embolism, volume overload and the precipitation
      of congestive heart failure, cardiac tamponade from catheter perforation or from
      steam pop with RF energy delivery, valve or subvalvular support structure
      disruption, conduction system disruption with development of heart block,
      coronary artery injury when ablating in the coronary cusps region or trying to
      gain access to the LV chamber, precipitation of cardiogenic shock from ablation
      of viable myocardium in patients with marginal reserve and failure to resuscitate
      or precipitation of cardiogenic shock from repeated VT induction, and with
      epicardial ablation the potential complications of epicardial access, coronary
      arteries and phrenic nerve damage. Recognition of these risks is paramount for
      their avoidance with careful pre-procedure planning and intraprocedural technique
      being essential to minimize the potential for complications.

PMID- 18084797
TI  - [Strategies for the avoidance and treatment of complications during pacemaker
      implantation].
AB  - The implantation of a pacemaker is the therapy of choice for symptomatic
      bradyarrhythmias. The perioperative complication rate is low. This article gives
      an overview on possible complications, their avoidance and treatment.

PMID- 18084798
TI  - What can happen during coronary sinus lead implantation: dislocation, perforation
      and other catastrophes.
AB  - Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is an
      established method for the therapy of congestive heart failure (CHF) in the case
      of asynchronous ventricular contractions. Successful therapy depends on the
      placement of left ventricular leads usually via the coronary sinus (CS), a
      technically more challenging procedure than regular pacemaker implantations.
      Without specific precautions CRT implantation can be the gateway to a time
      consuming nightmare. Therefore CS lead implantation methods, with a focus on
      complications, were reviewed according to the literature and own experience with
      approximately 500 procedures from 1999-2007.

PMID- 18084799
TI  - Bifocal versus unifocal right atrial pacing under plasma level controlled sotalol
      to prevent atrial fibrillation in patients with symptomatic sinus bradycardia and
      paroxysmal atrial fibrillation.
AB  - AIMS: Bifocal right atrial pacing (BP) has been reported to increase arrhythmia
      free intervals in patients with paroxysmal atrial fibrillation (PAF) under
      antiarrhythmic drugs. This study compares AF burden with unifocal pacing (UP) vs
      BP under sotalol. METHODS: In 19 patients with PAF a DDDR pacemaker with right
      atrial lateral and CS ostial leads was implanted. Sotalol was initiated. After a
      3 month back-up pacing period patients were randomized to continuous UP or BP for
      3 months and crossed over for 3 more months. Primary endpoint was AF burden.
      Secondary endpoints included number of episodes, time to first recurrence and
      safety of BP. RESULTS: The intention to treat analysis revealed 12.4% AF during
      back-up, 6.2% during UP and BP (p=0.91 UP vs BP, p=0.08 back-up vs UP and p=0.07
      back-up vs BP). Per protocol analysis showed no advantage of either pacing mode
      (UP 4.8% and BP 5.4% AF, p=0.64). Overdrive pacing reduced AF burden to 6.2 vs
      8.8% during back-up (p=0.09). Septal lead dislodgement occurred in 3 patients.
      CONCLUSION: Atrial pacing tends to reduce AF burden in patients with PAF under
      sotalol. An incremental effect of BP vs UP cannot be confirmed. BP may be
      complicated by elevated lead dislodgement rates.

PMID- 18084801
TI  - [Causes of pauses].
AB  - We discuss the electrocardiogram and differential diagnosis of an apparent type
      II second-degree atrioventricular block recorded in a 15-year-old girl after
      successful radiofrequency ablation of a left-sided concealed accessory pathway.

PMID- 18084800
TI  - [Outcome parameters for AF trials--executive summary of an AFNET-EHRA consensus
      conference].

PMID- 18084807
TI  - A clinical, electrophysiological, and pathological study of neuropathy in
      rheumatoid arthritis.
AB  - Neuropathy in rheumatoid arthritis (RA) may result secondary to entrapment,
      vasculitis, and drug toxicity. We aimed to study clinical and
      electrophysiological neuropathy and pathological changes in sural nerve in
      patients with RA. One hundred eight patients of RA, fulfilling American College
      of Rheumatology 1987 criteria (mean age, 45.83 years; M/F 1:3, 80.3%
      seropositive) were examined clinically and electrophysiologically for evidence of
      peripheral neuropathy. Sural nerve biopsies were performed in the involved cases.
      In all RA patient medications, disease activity, results of blood tests, and X
      rays of affected joints were recorded. Twenty-three patients complained of
      paresthesias in the extremities. Vibration sensations were decreased in 9, and
      tendon reflexes were decreased or absent in 28 patients. Sixty-two (57.4%)
      patients had electrophysiologic evidence of neuropathy. Of these 53 (85.5%)
      patients had pure sensory or sensory motor axonal neuropathy (mononeuritis
      multiplex, n = 7), while 9 (14.5%) had demyelinating neuropathy (chronic
      inflammatory demyelinating polyneuropathy, n = 1). Carpal tunnel syndrome was
      seen in 11 (10.1%) patients (associated with neuropathy in 6). Of 23 sural nerve
      biopsies available, perineurial thickening (n = 5, amyloid deposits n = 4),
      perivascular lymphomononuclear cell infiltrate (n = 4), loss of myelin fibers (n
      = 2), and necrotizing vasculitis (n = 1) were found. Clinically, however, seven
      patients had evidence of cutaneous vasculitis. Comparing the clinical
      characteristics of the patients with or without electrophysiological neuropathy,
      absence of deep tendon jerks (p < 0.005) and presence of extra articular
      manifestations (p < 0.01) were conspicuous in the neuropathic group. There was no
      relation of neuropathy with the duration of RA, seropositivity, joint erosions,
      joint deformities, prior disease-modifying anti-rheumatic drugs or glucocorticoid
      intake, and 28-joint disease activity score. Neuropathy in RA was mostly
      subclinical and predominantly axonal. Pathologically, neuropathy secondary to
      amyloid infiltration was second only to vasculitic neuropathy. Absence of deep
      tendon jerks and presence of vasculitis were more commonly observed in patients
      with neuropathy.

PMID- 18084808
TI  - Effect of low-intensity laser therapy on mast cell degranulation in human oral
      mucosa.
AB  - Little is known about the physiological mechanisms related to low-intensity laser
      therapy (LILT), particularly in acute inflammation and subsequent wound healing.
      The objective of this study was to verify the effect of LILT on mast cell
      degranulation. Epulis fissuratum tissues from eight patients were used. One part
      of the lesion was irradiated with an AsGaAl laser (lambda = 670 nm, 8.0 J/cm(2),
      5 mW, 4 min). The other part was not irradiated. Then, the specimens were
      immediately removed, fixed and examined by light microscopy. The number of mast
      cells was similar in laser-treated samples when compared with non-irradiated
      specimens. The degranulation indexes of the mast cells observed in the irradiated
      samples were significantly higher than those of controls (P < 0.05). LILT with
      the parameters used increased the number of degranulated mast cells in oral
      mucosa.

PMID- 18084809
TI  - Impact of intense pulse light irradiation on BALB/c mouse skin-in vivo study on
      collagens, matrix metalloproteinases and vascular endothelial growth factor.
AB  - Our aim was to investigate the effects of intense pulsed light (IPL) on collagen
      expression in BALB/c mouse skin and confirm its relative molecular mechanisms.
      The dorsal skin of BALB/c mice was irradiated by IPL. Before treatment and from 1
      day to 8 weeks (1 day, 3 days, 5 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks
      and 8 weeks) after treatment, the irradiated skin specimens were examined. The
      histology showed dermis thickening, accompanied with increased collagen and
      better organization. After IPL irradiation from 2 W up to 8 W, the staining of
      collagen types I and III in the IPL-treated groups was stronger than in the sham
      groups (P < 0.05), and the mRNA expression levels of the procollagen types I and
      III had also increased (P < 0.05). The up-regulation effects of IPL irradiation
      were time-dependent. The mRNA expression levels of matrix metalloproteinase (MMP)
      1 and MMP-2 decreased progressively after IPL irradiation at 2 W up to 8 W (P <
      0.05), and this down-regulation effect of IPL was also time-dependent. However,
      the mRNA expression of vascular endothelial growth factor (VEGF) had shown no
      obvious change by the end of the experiment (P > 0.05). Taking these factors
      together, we can conclude that IPL irradiation can not only enhance new collagen
      production, but also decrease collagen degradation in photo-rejuvenation
      mechanisms in mouse skin.

PMID- 18084810
TI  - Temperature rise during photo-activated disinfection of root canals.
AB  - The aim of this study was to determine whether it is safe to use photo-activated
      disinfection (PAD) during root canal treatment without heating the periodontal
      tissues. Root canals of 30 freshly extracted single-rooted teeth were prepared
      using ProFiles up to size ISO 40 and then filled with photo-sensitiser: tolonium
      blue (1.2 mg/l). The 635 nm diode laser was used with the manufacturer's endo
      tip. Samples were irradiated for 150 s (output power 100 mW, approximate energy
      density 106.16 J/cm(2)). Temperatures were recorded at working length on the
      external root surface. After 150 s of PAD irradiation, the average temperature
      rise was 0.16 +/- 0.08 degrees C. All values were lower than the 7 degrees C
      safety level for periodontal injury. It was concluded that, regarding the
      temperature increase, the use of PAD in root canals could be considered harmless
      for periodontal tissues.

PMID- 18084812
TI  - Evidence-based imaging of the nervous system.

PMID- 18084811
TI  - Acute renal failure and outcome of children with solitary kidney undergoing
      cardiac surgery.
AB  - The aim of this study was to investigate the risk of acute renal failure (ARF),
      the need for renal replacement therapy, and the outcome of children with a
      solitary functioning kidney undergoing open heart surgery. The study was
      performed retrospectively on all children diagnosed with solitary functioning
      kidney and who required open heart surgery between January 2003 and January 2007.
      Demographic, perioperative renal function and intensive care course data were
      documented. Eight patients (six females) fulfilled the study criteria and were
      included in the study. Their median age and weight were 4.5 months and 3.6 kg,
      respectively. Their mean +/- standard deviation (SD) preoperative blood urea
      nitrogen (BUN) and creatinine levels were 3.7 +/- 1.6 mmol/L and 55 +/- 10
      micromol/L, respectively. Postoperatively, the mean BUN and creatinine levels
      peaked on the first postoperative day to reach 7.8 +/- 2.6 mmol/L and 76 +/- 22
      micromol/L, respectively, before starting to return to their preoperative values.
      Two out of eight patients (25%) developed ARF after surgery, but only one of them
      (12.5%) required renal replacement therapy. Open heart surgery on bypass can be
      performed safely for children with solitary functioning kidney with a good
      outcome. ARF requiring renal replacement therapy might occur temporarily after
      bypass surgery in a minority of cases.

PMID- 18084813
TI  - New York University names Robert Grossman Dean and Chief Executive Officer.

PMID- 18084814
TI  - Epoetin alfa in critically ill patients.

PMID- 18084815
TI  - Epoetin alfa in critically ill patients.

PMID- 18084816
TI  - Persistent dizziness after surgical treatment of vertigo: an exploratory study of
      prognostic factors.
AB  - OBJECTIVE: Persistent vertigo and imbalance can occur after surgery for vertigo
      regardless of surgical approach. This study explored for factors affecting
      outcome of vertigo surgery. STUDY DESIGN: Patient survey and chart review.
      SETTING: Tertiary referral neurotologic private practice. PATIENTS/INTERVENTION:
      Of 111 patients (57.7% female; mean age, 52.3 yr), 59 underwent vestibular nerve
      section (middle fossa, retrolabyrinthine, and translabyrinthine), 25 underwent
      transmastoid labyrinthectomy, and 27 underwent endolymphatic sac shunt. Eighty
      three percent had Meniere's disease. Mean follow-up was 4.3 years. MAIN OUTCOME
      MEASURES: Primary outcomes included American Academy of Otolaryngology-Head and
      Neck Surgery (AAO-HNS) vertigo score and class, number of spells per month,
      current and change in AAO-HNS disability rating, vertigo and imbalance severity
      ratings, and frequency of imbalance. RESULTS: Three preoperative factors were
      consistently related to outcome: AAO-HNS disability rating, imbalance frequency
      rating, and duration of first symptom ([rho] = 0.19-0.51; all p's < 0.05).
      Greater disability and more frequent imbalance related to poorer outcome, but
      longer duration of disease related to better outcome. Presurgery vertigo
      characteristics were generally not related to outcome. Meniere's patients were
      more likely to have improvement in imbalance, as were those with no other
      significant disease and no allergy. The presence of tinnitus in the contralateral
      ear was associated with poorer outcomes, including a lower rate of results of
      Classes A and B (p = 0.023). Vertigo as a first symptom and the presence of eye
      disease also showed relationships to poorer outcome. CONCLUSION: Those rating
      themselves as more disabled before surgery are less likely to achieve the best
      outcomes, whereas frequency and severity of preoperative vertigo are not
      predictive. Several possible prognostic factors were identified that warrant
      future prospective study.

PMID- 18084817
TI  - Low-tidal-volume ventilation.

PMID- 18084818
TI  - Determining subjective visual vertical: dynamic versus static testing.
AB  - OBJECTIVE: Comparative evaluation of two tests that, as a visual reference,
      respectively use a static light source (static testing) and a dynamic one
      (dynamic testing) to analyze subjective visual vertical in patients with
      unilateral vestibular dysfunction. STUDY DESIGN: Prospective study. SETTING:
      Otolaryngology and Cervicofacial Surgery Division, Department of Medical-Surgical
      Specialization, University of Perugia, Italy. PATIENTS: Forty-two patients with
      unilateral vestibular dysfunction. INTERVENTIONS: Determination of subjective
      visual vertical 1 to 2 days (first test) after the onset of vertigo. Repetition
      of 8 to 10 days (second test) and 90 days (third test) after onset. MAIN OUTCOME
      MEASURES: Test sensitivity and specificity. RESULTS: The sensitivity of the
      static test was 85.7, 73.3, and 59.5% during the first, second, and third test,
      respectively. The dynamic test showed a sensitivity of 91.3, 86.8, and 78.1%,
      respectively. Specificity was 100% for the static test and 96.7% for the dynamic
      test. CONCLUSION: The dynamic test proved to be more useful in the weeks after
      the onset of dysfunction. Given the greater sensitivity of this test, the
      reduction in perception error time makes it more suitable for revealing false
      negatives that emerged when using the static test alone.

PMID- 18084819
TI  - Mechanical obstruction of the eustachian tube by the benign tumor of the
      parapharyngeal space does not cause otitis media with effusion.
AB  - OBJECTIVE: We are reporting on eustachian tube and middle ear pathologic findings
      in patients with parapharyngeal tumors. PATIENTS: Eleven cases of eustachian tube
      involvement as indicated by obstruction due to compression of the tumor were
      assessed in this study. MAIN OUTCOME MEASURES: Each patient underwent otoscopy,
      nasopharyngoscopy, a pure-tone hearing test, impedance audiometry, and
      sonotubometry. RESULTS: All of the tumors were diagnosed benign according to the
      histologic examination. In 9 of the 11 patients, the pharyngeal opening of the
      eustachian tube narrowed or was blocked by the tumor. None of the patients showed
      any response on the tumor side in the sonotubometry. Therefore, gas exchange was
      prevented through the eustachian tube by the tumor; however, they also showed an
      intact tympanic membrane and normal hearing tests. CONCLUSION: According to our
      data, if there is drainage of middle ear fluid through the eustachian tube and
      the exchange of gas in the middle ear is preserved, otitis media with effusion
      will not occur even in cases such as these.

PMID- 18084820
TI  - Reading my father: a writer's triumphs and his torments.

PMID- 18084821
TI  - The checklist: if something so simple can transform intensive care, what else can
      it do?

PMID- 18084822
TI  - MRSA-contaminated ambulance.

PMID- 18084823
TI  - Unilateral congenital facial nerve paralysis secondary to a benign epithelioid
      peripheral nerve sheath tumor.
AB  - OBJECTIVE: A benign epithelioid peripheral nerve sheath tumor is described in the
      setting of congenital facial nerve (FN) paralysis. This is the first reported
      case in the English literature. PATIENT: A 10-month-old girl with unilateral
      congenital FN paralysis. INTERVENTIONS: Auditory brainstem evoked potential
      study, gadolinium-enhanced magnetic resonance imaging, temporal bone computed
      tomography, and transmastoid FN decompression with tumor resection. MAIN OUTCOME
      MEASURES: Follow-up for tumor recurrence and postoperative FN function. RESULTS:
      The child underwent a transmastoid FN exploration with resection of a 0.6-cm
      spherical tumor analyzed to be a benign epithelioid peripheral nerve sheath
      tumor. There is no evidence of recurrence, and FN function was unchanged at 1
      year postoperatively. CONCLUSION: Benign epithelioid peripheral nerve sheath
      tumor can cause congenital facial nerve palsy.

PMID- 18084824
TI  - Keratinocyte-derived chemokine plays a critical role in the induction of systemic
      inflammation and tissue damage after trauma-hemorrhage.
AB  - Neutrophil infiltration is a crucial step in the development of organ dysfunction
      after trauma. We have previously shown that keratinocyte-derived chemokine (KC),
      a chemoattractant for neutrophils, is up-regulated after trauma-hemorrhage. To
      determine the role of KC after trauma-hemorrhage, the effect of a KC-neutralizing
      antibody on the posttraumatic inflammatory response was examined. One hour before
      surgery, male C3H/HeN mice were treated with an anti-KC antibody or isotype
      control. Animals were subjected to sham operation or trauma-hemorrhage and
      resuscitated with Ringer lactate thereafter. They were killed 2 h later, and
      Kupffer cells were isolated. Plasma levels, Kupffer cell production, and lung and
      liver content of TNF-alpha, IL-6, IL-10, monocyte chemoattractant protein 1,
      macrophage inflammatory protein 1alpha, and KC were determined by BD cytometric
      bead arrays. Myeloperoxidase content in lung and liver were measured as a
      parameter for neutrophil infiltration, and wet-to-dry weight ratios of these
      organs were also determined. Hepatocyte damage was assessed by measuring alpha
      gluthathione S-transferase concentration. Administration of the anti-KC antibody
      before trauma-hemorrhage prevented increases in KC plasma levels, which was
      accompanied by amelioration of neutrophil infiltration and edema formation in
      lung and liver after trauma-hemorrhage. No effect on other cytokines in plasma or
      Kupffer cell release was observed. These results suggest that KC plays a pivotal
      role in neutrophil infiltration and organ damage after trauma-hemorrhage and
      resuscitation.

PMID- 18084825
TI  - The Arabidopsis circadian clock incorporates a cADPR-based feedback loop.
AB  - Transcriptional feedback loops are a feature of circadian clocks in both animals
      and plants. We show that the plant circadian clock also incorporates the
      cytosolic signaling molecule cyclic adenosine diphosphate ribose (cADPR). cADPR
      modulates the circadian oscillator's transcriptional feedback loops and drives
      circadian oscillations of Ca2+ release. The effects of antagonists of cADPR
      signaling, manipulation of cADPR synthesis, and mathematical simulation of the
      interaction of cADPR with the circadian clock indicate that cADPR forms a
      feedback loop within the plant circadian clock.

PMID- 18084827
TI  - A magnetic immunochromatographic strip test for detection of human papillomavirus
      16 E6.

PMID- 18084826
TI  - Long-term vertigo control in patients after intratympanic gentamicin instillation
      for Meniere's disease.
AB  - OBJECTIVES: To assess long-term vertigo symptom control in patients after
      intratympanic gentamicin instillation for incapacitating unilateral Meniere's
      disease. To analyze whether an absent caloric response, as analyzed using
      electronystagmography after gentamicin treatment, is a good predicator of long
      term symptom control. Finally, to quantify the patient's perception of long-term
      posttreatment handicap. STUDY DESIGN: A retrospective study from a single
      institution. All patients underwent a similar fixed-dose and duration protocol of
      drug instillation. METHODS: Patients were enrolled in this study, and initial
      outcomes were assessed according to the American Academy of Otolaryngology-Head
      and Neck Surgery Committee on Hearing and Equilibrium Guidelines for Reporting
      Treatment Results in Meniere's Disease (1985 and 1995). In this study, only those
      patients treated more than 5 years previous were considered. One hundred thirty
      two patients were eligible for inclusion. All patients underwent hearing testing
      and electronystagmography, including caloric testing before and after treatment.
      Posttreatment handicap and long-term vertigo control were assessed using the
      Dizziness Handicap Index questionnaire expanded with 5 questions specific for
      Meniere's disease. RESULTS: Analysis of results is based on the 63 patients who
      responded. Forty-four were vertigo-free, whereas 14 continued to experience some
      degree of vertigo. On average, they described 5 episodes in the immediate 24
      months before the study. Of the 44 patients who were asymptomatic, 35 had an
      absent caloric response. Of the 14 patients who realized some vertigo, 12 had an
      absent caloric response posttreatment. Of the 63 responders, 44 filled in the
      Dizziness Handicap Index. Of the 19 who did not, 17 reported that they were
      vertigo-free. CONCLUSION: Our current protocol achieves complete or substantial
      vertigo control in most patients. A significant caloric response reduction has
      been a consequence in almost all patients, although an absent caloric response is
      not invariably a predictor of long-term symptom control. Finally, patient
      perceived handicap in this long-term follow-up is consistent with that of others
      followed for a much shorter duration in that those who were vertigo-free
      volunteered a significantly lower score.

PMID- 18084828
TI  - [The distribution of HLA genes in Russian patients with germ cell tumors].
AB  - The correlation between DRB1, DQA1, and DQB1 genes of HLA class II, and the
      development of germ cell tumors (GCTs), as well as serological response to HERV-K
      proteins were investigated. Genomic DNA prepared from 99 GST patients was
      subjected to HLA typing by polymerase chain reaction (PCR) using the set of
      sequence specific primers (PCR-SSP). This set of primers made it possible to
      detect 14 specificities of DRB 1 locus, 12 alleles and groups of alleles of DQB 1
      locus, and 8 alleles of DQA1 locus. Alongside with the definition of the
      occurrence of HLA markers in the total group of patients, the frequency of the
      occurrence of HLA-DR-DQ alleles was calculated in: 1) patients with different
      morphological forms of GSTs (seminomas and non-seminomas); 2) GCT patients
      producing or non-producing antibodies to Gag and/or Env HERV-K proteins. The
      comparison group consisted of 300 Moscow blood donors. The study did not reveal
      statistically significant differences in the frequency of the occurrence of DRB1,
      DQA1, and DQB1 alleles between the total group of GCT patients, its subgroup, and
      the control group. Thus, the data obtained demonstrated the absence of a strict
      correlation between the distribution of HLA class II alleles and GCT occurrence
      in the Russian population, as well as the ability of GCT patients to develop an
      antibody to HERV-K proteins, though more numerous observations are required to
      confirm this conclusion.

PMID- 18084829
TI  - [Bcl-2 family proteins and mechanisms of the acceleration and inhibition of tumor
      progression in vivo].
AB  - Earlier the authors demonstrated that the process of tumor progression in vivo
      may be inhibited or accelerated depending on the conditions of tumor growth
      (accelerated by tumor cell dissemination or delayed in locally growing tumors).
      It was also shown that tumor progression is inhibited in case of bcl-2 gene
      transduction in tumor cells. In this study, the research into mechanisms of the
      acceleration or inhibition of tumor progression and the role that Bcl-2 family
      proteins may play in these phenomena was continued. The results of the study
      demonstrated the following 1) immediate in vivo activation of endogenous
      proapoptotic Bax protein in disseminated tumor cells, not protected by Bcl-2
      against apoptosis, and its correlation with accelerated tumor progression; 2)
      complete suppression of in vivo Bax activation in tumor cells protected by Bcl
      expression, and inhibited tumor progression; 3) alternative character of Bcl-2
      and Bax expression under the conditions of accelerated and inhibited tumor
      progression. Thus, the data presented support the hypothesis that the rates of
      tumor progression in vivo are regulated depending on the initial anti- and
      proapoptotic programs of tumor cells.

PMID- 18084831
TI  - [Impaired emotional sphere in patients with infiltrative pulmonary tuberculosis].
AB  - The emotional sphere was studied in 100 patients with infiltrative pulmonary
      tuberculosis. They were ascertained to have anxiety and depressions the degree of
      which largely reflected the severity of the patients' clinical. The depressive
      libido loss index was shown to make a valid prediction of decay cavity closure 4
      months after the initiation of antituberculous therapy.

PMID- 18084830
TI  - [The purification of the protein alternative to alfa-fetoprotein].
AB  - The subject of the study was the unidentified protein Ag A2/3, which is found in
      some cells of rat hepatoma McA RH7777 and their clones. The feature of this
      protein is that its expression is alternative to alfa-fetoprotein (AFP), i.e. Ag
      A2/3 is not found in cells and cell clones containing AFP, and vice versa. Ag
      A2/3 proved to be a cell stress protein--it was induced by heavy metal salts
      (Pb2+ and Cd2+) in the liver of adult rats and AFP+/A2/3(-) clones of hepatomas;
      the attenuation of AFP synthesis occurred simultaneously. This paper describes
      the preparation of Ag A2/3 for sequence analysis, and the scheme of Ag A2/3
      purification. When trying to obtain a blot for sequencing it proved to be
      impossible to reveal the protein using McAb to Ag A2/3 after the transfer of
      separated proteins on PVDF. The reactivity of the antigen determinant was
      reestablished with blot processing on PVDF membrane with methanol and Twin 80.

PMID- 18084832
TI  - [Examination of personality and emotional-volitional disorders in the homeless
      with tuberculosis].
AB  - In persons with impaired social regulation, the balance of value-need regulation
      is shifted towards the predominance of needs. Directions in their life are absent
      or their set is very limited. Their behavior is frequently situation-dependent.
      Social and psychological dysadaptation results from that the individual
      inadequately appraises the life situation and hence inadequately responds to the
      latter. The socially unacceptable behavior becomes normal up to criminogenic
      (theft, violence). In the homeless with tuberculosis, a change occurs in the
      structural hierarchy of vital activity motives by the motive-for-objective type.
      In this connection, there is a paradoxical attitude towards the disease for the
      purpose of acquiring a social benefit. In the homeless, the factors that are
      frustrating and inducing stress in ordinarily persons cause no emotional
      responses. This was a result of the mental defense worked out under constant
      stress.

PMID- 18084833
TI  - [Extracorporeal antiaggregant pharmacotherapy in the treatment of acutely
      progressive forms of tuberculosis].
AB  - The investigation was undertaken to study whether extracorporeal pharmacotherapy
      with the antiaggregant pentoxiphylline (trental) might be used to correct blood
      rheological disorders in the early combined treatment of 32 patients with acutely
      progressive destructive tuberculosis, including 15 patients with caseous
      pneumonia. The method is based on the administration of in vitro drug-treated
      autologous blood cells. Two-three-week extracorporeal pharmacotherapy with the
      antiaggregant pentoxiphylline substantially improved pulmonary microcirculation
      and made the laboratory values of hypercoagulation and endotoxicosis better. The
      method promoted accelerated regression of the clinical and X-ray manifestations
      of the disease in 27 of the 32 patients. Few observations lead to a preliminary
      conclusion that this method positively affects the results of treatment for
      acutely progressive forms of tuberculosis, including those of treatment for
      caseous pneumonia.

PMID- 18084834
TI  - [Diagnostic features and efficiency of treatment in nonbacteria-isolating
      patients with pulmonary tuberculosis].
AB  - In patients with pulmonary tuberculosis with negative sputum bacterioscopic
      tests, the diagnosis of tuberculosis may be verified by supplementary studies:
      sputum inoculation, polymerase chain reaction, medium inoculation,
      bronchoalveolar lavage, smear microscopy, blood medium inoculation, determination
      of serum antigens and antibodies. The patients in whom sputum Mycobacterium
      tuberculosis has not been detectable by bacterioscopy, the diagnosis of
      tuberculosis established by X-ray tomography and verified by supplementary
      studies should receive chemotherapy (primarily WHO Category 3 chemotherapy). An
      algorithm is proposed to diagnose tuberculosis in patients with three negative
      smear microscopic tests.

PMID- 18084836
TI  - [Regional Scientific-and Practical Conference "once more about the detection and
      diagnosis of tuberculosis"].

PMID- 18084835
TI  - [Use of molecular genetic studies to determine the species of the mycobacteria
      mais and M. tuberculosis complex].
AB  - The genus Mycobacterium currently comprises more than 90 species of
      Mycobacterium, of which a third is able to induce human diseases. With a rise in
      the incidence of diseases induced by non-tuberculosis mycobacteria, tuberculosis
      caused by M. bovis that is characterized by a severe cause and a high frequency
      of poor outcomes cannot be remembered. The species of mycobacteria should be
      identified to establish a diagnosis and to prescribe adequate chemotherapy. For
      this purpose, cultural, biochemical, chromatographic, and molecular genetic
      studies are conducted. The present study using the hsp65 gene restriction
      fragment length polymorphism test on museum mycobacterial strains and strains
      isolated from the diagnostic material of patients with suspected tuberculosis by
      means of Hind61 restrictase has provided a clear differentiation of the
      restriction profiles of MAIS complex mycobacteria and some other species of non
      tuberculosis mycobacteria. To determine the species of representatives of M.
      tuberculosis complex (M. tuberculosis, M. bovis, BCG M. bovis), the authors have
      successfully used the test system "TUB-dif" developed at the Institute of
      Molecular Genetics, Russian Academy of Sciences, by applying the chain polymerase
      reaction of the senX3-regX3 region.

PMID- 18084837
TI  - Dehydrocoupling of dimethylamine-borane catalysed by rhenium complexes and its
      application in olefin transfer-hydrogenations.
AB  - Re(I) complexes are applied as catalysts for the dehydro-coupling of Me2NH.BH3
      and the transfer-hydrogenation of olefins.

PMID- 18084838
TI  - Re: Value of biopsy in the assessment of a retroperitoneal mass. Chew et al.
      Surgeon 2006; 4: 2; 79-81.

PMID- 18084839
TI  - Biomarker evidence of myocardial cell injury is associated with mortality in
      acute respiratory distress syndrome.
AB  - OBJECTIVE: Although a number of studies have reported elevated levels of markers
      of myocardial necrosis among critically ill patients, the association between
      these markers and outcome remains poorly studied in patients with lung injury. We
      investigated the association of elevated troponin and creatine phosphokinase
      isoenzyme levels with mortality and organ failure in subjects with acute
      respiratory distress syndrome. DESIGN: Retrospective study. SETTING: Tertiary
      academic medical center. PATIENTS: A total of 305 subjects with acute respiratory
      distress syndrome enrolled in a prospective intensive care unit cohort.
      INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Cardiac biomarker data were
      available on 248 of 305 patients with acute respiratory distress syndrome (81%),
      of which 89 patients had at least one elevated cardiac marker level (35%). The
      presence of an elevated cardiac marker was associated with significantly higher
      mortality (p = .01) and was an independent predictor of mortality (p = .02) among
      patients with lower severity of illness (Acute Physiology and Chronic Health
      Evaluation III, <79). Patients with at least one elevated cardiac marker also had
      significantly more organ system derangement, including noncardiovascular organ
      system failures (p = .02). CONCLUSIONS: Patients with acute respiratory distress
      syndrome have a high prevalence of elevated cardiac markers. The presence of
      elevated cardiac markers is independently associated with increased 60-day
      mortality and increased organ failure. This association is most pronounced among
      patients with lower severity of illness. These results indicate that occult
      myocardial injury may be an important factor in acute respiratory distress
      syndrome morbidity and mortality. Further study of the relevant causal
      relationships and mechanisms is warranted.

PMID- 18084840
TI  - The efficacy of loop diuretics in acute renal failure: assessment using Bayesian
      evidence synthesis techniques.
AB  - OBJECTIVE: To quantify the therapeutic efficacy of loop diuretics in acute renal
      failure using Bayesian evidence synthesis, because despite widespread use, the
      role of diuretics is controversial. DATA SOURCE: Randomized controlled trials or
      nonrandomized studies, 1966 to January 2007, identified from MEDLINE and EMBASE
      databases and manual bibliographic search. STUDY SELECTION: Studies with
      assessable predefined end points, exclusive of those pertaining to acute renal
      failure prophylaxis or chronic renal failure. DATA EXTRACTION: Data extraction
      was performed jointly by the first two authors; independent study assessment was
      via standard checklist, unblinded. DATA SYNTHESIS: The primary outcome was
      mortality; secondary outcomes were time to renal function normalization and total
      number of dialyses. Bayesian hierarchical random effects estimates of treatment
      effects were determined as risk ratio for mortality, incidence rate ratio for
      dialysis number, and mean difference for continuous measures. Bayesian outcome
      probabilities were calculated as probability (P) that risk ratio or incidence
      rate ratio of loop diuretics >1 and probability that mean difference >0. Five
      randomized controlled trials and eight nonrandomized studies were identified.
      Loop diuretics were not associated with decreased mortality in either randomized
      controlled trials or nonrandomized studies: overall risk ratio 1.10; 95% credible
      interval 0.85, 1.42; P(risk ratio >1) > 83.8%. The oliguric period was decreased
      by loop diuretics: overall mean difference -7.70 days; 95% credible interval 
      12.51, -2.08; P (mean difference >0) = 0.7%. Although the dialysis rate credible
      interval, loop diuretics vs. control, spanned unity (incidence rate ratio 0.71;
      95% credible interval 0.47, 1.06), the probability that the incidence rate ratio
      exceeded unity indicated a substantial benefit: P (incidence rate ratio >1 =
      4.1%. Uremic duration was not substantially different, loop diuretics vs.
      control: overall mean difference -1.54 days; 95% credible interval -5.62, 2.46; P
      [mean difference >0] = 17.8%). CONCLUSIONS: Loop diuretics were not associated
      with improved survival benefit in acute renal failure, despite reduction in
      oliguric period and high probability of a significant reduction in dialysis
      numbers. Further studies to clarify this dichotomy appear mandated.

PMID- 18084841
TI  - Individual delirium symptoms: do they matter?
AB  - OBJECTIVES: To evaluate the impact of individual manifestations of delirium on
      outcome, describe them in critically ill adults, and validate nurses' bedside
      item assessments from the Intensive Care Delirium Screening Checklist (ICDSC).
      DESIGN: Prospective study. SETTING: Single 16-bed medical/surgical university
      hospital intensive care unit. PATIENTS: Six hundred consecutive patients admitted
      to the intensive care unit for >24 hrs. INTERVENTIONS: All patients were
      evaluated with the eight-item ICDSC throughout their intensive care unit stay. In
      all patients scoring positive on any ICDSC item, individual checklist items were
      tallied throughout the intensive care unit stay and assessed for impact on
      mortality. In addition, when the ICDSC score indicated delirium (> or = 4 of 8),
      the subsequent overall frequency of each item was also independently documented
      to describe delirious patient symptoms. ICDSC items were tested for
      discrimination between delirious and nondelirious patients. Throughout the study,
      the validity of bedside delirium assessments was assessed in 30 nurses.
      MEASUREMENTS AND MAIN RESULTS: We were able to assess 537 patients. In
      nondelirious patients, psychomotor agitation by ICDSC assessment was associated
      with a higher risk of mortality after adjustment for Acute Physiology and Chronic
      Health Evaluation, age, and the presence of coma. One hundred eight-nine patients
      (35.1%) developed delirium (i.e., ICDSC score > or = 4). On presentation (and
      throughout the intensive care unit stay), the most frequent features of delirium
      were inattention, disorientation, and psychomotor agitation. Each ICDSC item was
      highly discriminating between delirious vs. nondelirious patients. Correlation
      between gold standard adjudicators and nurses for the overall bedside evaluations
      of delirium were excellent (Pearson's correlation R = 0.924, p < .0005).
      Individual symptom evaluation by nurses varied: Alteration in level of
      consciousness was poorest (R = 0.681, p < .0005), and both disorientation and
      hallucinations evaluated best (R = 1.000). CONCLUSIONS: In nondelirious patients,
      agitation was associated with a higher risk of mortality. Each of the eight ICDSC
      items is highly discriminating for the diagnosis of delirium, suggesting that any
      screening or diagnostic scales should incorporate them. Quality assurance and
      educational efforts should, therefore, emphasize independent assessment of the
      individual features of delirium.

PMID- 18084842
TI  - Bibliography. Current world literature. Antimicrobial agents: viral/parasite.

PMID- 18084843
TI  - The validity of the GPRI.

PMID- 18084844
TI  - [Report from the 25th International Congress of Chemotherapy and the 17th
      European Congress of Clinical Microbiology and Infectious Diseases].

PMID- 18084845
TI  - [The history and current potential of diagnostic laparoscopy].

PMID- 18084846
TI  - [The majority may not always be right].

PMID- 18084847
TI  - Bay w 9798, a dihydropyridine structurally related to nifedipine with no calcium
      channel-blocking properties, inhibits tumour necrosis factor-alpha-induced
      vascular cell adhesion molecule-1 expression in endothelial cells by suppressing
      reactive oxygen species generation.
AB  - Dihydropyridine-based calcium antagonists (DHPs) are widely used to treat
      hypertension. We have previously shown that nifedipine, one of the most popular
      DHPs, blocks tumour necrosis factor-alpha (TNF-alpha)-induced monocyte
      chemoattractant protein-1 as well as vascular cell adhesion molecule-1 (VCAM-1)
      expression in endothelial cells by suppressing reactive oxygen species generation
      (ROS). The molecular mechanism is still to be elucidated, however, because
      endothelial cells do not possess voltage-operated L-type calcium channels. The
      aim of this study was to determine in TNF-alpha-exposed human umbilical vein
      endothelial cells (HUVECs) whether and how Bay w 9798, a dihydropyridine
      structurally related to nifedipine with no calcium antagonistic properties, may
      suppress VCAM-1 expression, a key molecule which mediates the adhesion of
      monocytes to vasculature in the early stages of atherosclerosis. In HUVECs, 10
      ng/ml TNF-alpha for 4 h stimulated ROS generation and subsequently upregulated
      VCAM-1 mRNA levels, both of which were dose-dependently blocked by Bay w 9798.
      The results demonstrated that Bay w 9798 inhibited VCAM-1 expression in TNF-alpha
      exposed cells by suppressing ROS generation. They suggest that the anti
      inflammatory and anti-oxidative properties of nifedipine and Bay w 9798 may be
      ascribed to the dihydropyridine structure, which is common to both molecules and
      has no calcium antagonistic ability.

PMID- 18084848
TI  - Aqueous humour levels of asymmetric dimethylarginine (ADMA) are correlated with
      pigment epithelium-derived factor (PEDF) in patients with uveitis.
AB  - The association between the aqueous humour levels of asymmetric dimethylarginine
      (ADMA) and pigment epithelium-derived factor (PEDF) was evaluated. Aqueous humour
      levels of ADMA and PEDF were measured by high-performance liquid chromatography
      and enzyme-linked immunosorbent assay, respectively, in 31 uveitis samples and
      nine cataract control samples. Aqueous humour ADMA and PEDF levels were
      significantly higher in infectious and non-infectious uveitis patients than in
      controls (0.67+/-0.04 nmol/ml and 0.55+/-0.03 nmol/ml versus 0.43+/-0.04 nmol/ml
      for ADMA; 8.22+/-1.45 microg/ml and 5.22+/-0.95 microg/ml versus 1.32+/-0.22
      microg/ml for PEDF). A significant positive correlation between ADMA and PEDF
      levels in aqueous humour was found in control and uveitis patients. These results
      demonstrated that the aqueous humour level of ADMA is correlated with PEDF in
      humans and suggest that both ADMA and PEDF in aqueous humour may be elevated in
      response to inflammation in uveitis.

PMID- 18084849
TI  - Pigment epithelium-derived factor inhibits vascular endothelial growth factor
      induced vascular hyperpermeability both in vitro and in vivo.
AB  - Administration of pigment epithelium-derived factor (PEDF) inhibits advanced
      glycation end products-elicited retinal vascular hyperpermeability, as well as
      cold injury-induced brain oedema in rats. However, the underlying molecular
      mechanism by which PEDF blocks the hyperpermeability in vivo is not fully
      understood. This study investigated whether PEDF could inhibit vascular
      endothelial growth factor (VEGF)-induced vascular hyperpermeability both in vitro
      and in vivo. The Miles assay revealed that, after intradermal injection of VEGF
      in nude mice, simultaneous administration of PEDF inhibited vascular
      hyperpermeability in a dose-dependent manner. The in vitro permeability assay
      also showed that PEDF blocked the VEGF-induced barrier dysfunction in endothelial
      cells. These results demonstrated that PEDF could inhibit the VEGF-induced
      vascular hyperpermeability both in vitro and in vivo, and suggest that PEGF may
      be suitable to be considered as a novel therapeutic agent for various
      vasopermeable disorders in which VEGF is involved.

PMID- 18084850
TI  - The relationship between left ventricular mass index and insulin sensitivity,
      postprandial glycaemia, and fasting serum triglyceride and adiponection levels in
      patients with type 2 diabetes.
AB  - The relationship between left ventricular mass index (LVMI) and insulin
      sensitivity, postprandial glycaemia, fasting serum triglyceride and adiponectin
      was investigated in 70 patients with type 2 diabetes. Serum fasting insulin, C
      peptide, high-sensitivity C-reactive protein (hs-CRP), glycated haemoglobin
      (HbA1c), postprandial glycaemia, lipids and fasting serum adiponectin levels were
      measured. Ventricular hypertrophy was assessed at rest by electrocardiography and
      echocardiography. Insulin sensitivity was assessed using the homeostasis model
      assessment index (HOMA-IR). LVMI was assessed using the Devereux formula. Study
      patients had lower than normal HOMA-IR, and higher than normal serum fasting
      insulin levels and LVMI, and tended to have reduced insulin sensitivity.
      Pearson's correlation coefficient showed a statistically significant correlation
      between fasting serum adiponectin and LVMI, fasting serum insulin, HOMA-IR,
      HbA1c, serum postprandial glucose and hs-CRP. There were no statistically
      significant correlations between LVMI and serum hs-CRP or HOMA-IR. The results
      indicate the importance of fasting serum adiponectin in the development of
      cardiovascular complications, such as increased LVMI.

PMID- 18084851
TI  - [Abstracts of the XXXVII Congress of the Spanish Nephrology Society, 29 September
      2 October, 2007, Cadiz, Spain].

PMID- 18084852
TI  - Beyond nature-nurture.

PMID- 18084853
TI  - Dynamic development and dynamic education.

PMID- 18084854
TI  - Newer antipsychotics and the differences between clinical experiences and
      clinical trials. Interview by Norman Sussman, MD.

PMID- 18084855
TI  - Patient handout: Sleep disorders in the elderly.

PMID- 18084856
TI  - Management and treatment of chronic kidney disease.
AB  - Estimates suggest that 30 million Americans have some degree of chronic kidney
      disease. By 2030, more than 2.2 million people will require treatment for end
      stage renal disease, causing a significant impact on healthcare costs in the
      United States.

PMID- 18084857
TI  - Certification and credentialing to define competency-based practice.
AB  - One of the challenges that healthcare organizations face today is how to
      effectively establish, document, and evaluate competency in intravenous practice.
      The process used to define practice parameters based on national certification
      and credentialing versus organizational policies is described. Key attributes,
      the role of mentoring, and adverse outcomes are addressed.

PMID- 18084858
TI  - The right to health care in the United States: local answers to global
      responsibilities.

PMID- 18084859
TI  - Etoricoxib: new drug. Avoid using cox-2 inhibitors for pain.
AB  - (1) Paracetamol is the first-choice analgesic for joint pain. Nonsteroidal
      antiinflammatory drugs (NSAIDs), especially ibuprofen, are second-line options.
      Cox-2 inhibitors are no more effective than traditional NSAIDs and have no
      tangible advantages in terms of gastrointestinal tolerability. In contrast, they
      expose patients to an increased risk of cardiovascular adverse effects. (2)
      Etoricoxib is marketed in some European countries to relieve symptoms of
      osteoarthritis, rheumatoid arthritis, and gout attacks. (3) Many clinical trials
      have tested etoricoxib in these indications, as well as in ankylosing
      spondylitis, low back pain, and various types of acute pain. Etoricoxib was no
      more effective than other NSAIDs such as ibuprofen, naproxen or diclofenac in
      these situations. (4) Comparative trials showed a higher overall mortality rate
      with etoricoxib than with naproxen. A combined analysis of long-term comparative
      trials including 5441 patients, mainly versus naproxen, showed that etoricoxib
      does not reduce the risk of perforation, ulcer or severe gastrointestinal
      haemorrhage. Similarly, it does not reduce the risk of mild gastrointestinal
      events in at-risk patients: those with a history of gastrointestinal disorders,
      aspirin use, etc. (5) Three trials including a total of 34 701 patients (MEDAL
      programme) compared cardiovascular thrombotic events associated with etoricoxib
      and diclofenac. Overall, the cardiovascular risks appear to be similar but the
      thrombotic risk may be slightly higher with diclofenac than with other
      conventional NSAIDs. (6) Etoricoxib provoked arterial hypertension, oedema and
      heart failure during clinical trials. Serious skin reactions were reported both
      during clinical trials and after marketing, but their precise incidence is not
      known. Etoricoxib is partly metabolised by the cytochrome P450 isoenzyme CYP 3A4
      and increases the bioavailability of ethinylestradiol. (7) When a NSAID is
      considered, drugs with which we have the most experience should be chosen, such
      as ibuprofen, and used at the lowest acceptable dose regimen (daily dose and
      length of treatment). Etoricoxib should be avoided.

PMID- 18084860
TI  - Darier disease: a guide to the physician.
AB  - Darier disease is an autosomal dominant skin disorder, characterized by
      follicular and extrafollicular keratotic papules, primarily in seborrheic areas.
      It is caused by mutations of ATP2A2 gene, which encodes the sarco/endoplasmic
      reticulum Ca2+ ATPase isoform 2 (SERCA2 protein). SERCA pumps maintain low
      cytosolic Ca2+ concentration by actively transporting Ca2+ from the cytosol into
      the sarco/endoplasmic reticulum. The assembly of desmosomes in epithelial cells
      in vitro is initiated through an increase in the extracellular Ca2+ concentration
      but variations in intracellular Ca2+ are also thought to be important. To date,
      92 mutations of ATP2A2 gene in Darier disease patients have been identified,
      scattered throughout the gene. No hotspot mutation has been identified.
      Considerable phenotypic variations within and between families suggesting that
      compensatory mechanisms in intracellular Ca2+ homeostasis may include increased
      expression of the normal ATP2A2 allele and/or compensation by other SERCA pumps
      (SERCA1 and SERCA3). Alternatively, the activity of SERCA2 pumps required in
      different cutaneous areas may vary rapid depending on physiological and/or
      external factors.

PMID- 18084861
TI  - Hemophilia D factor (factor XII), red-cell deformability and platelet aggregates
      in raptors.
AB  - In a spectrum of raptorial birds hemorrheologic factors were determined compared
      to normal human values. Significant findings were that Hageman factor (factor
      XII) levels were very low, the red-cell filteration rate was low, but the
      platelet-aggregate ratio was in the normal range. Relatively large, nucleated red
      cells appeared to be less flexible-deformable--than normal human red cells.
      Microvessel density (MVD) appeared to be in the normal range, but increased
      average capillary diameter may explain the lack of microvascular abnormalities.
      Hageman factor deficiency in raptors is comparable to human hemophilia D.
      However, the mechanisms of the lack of obvious thromboembolic and/or hemorrhagic
      phenomena may require further investigation.

PMID- 18084862
TI  - Studies on splenic population size feedback control regulatory mechanisms.
AB  - In previous studies, experimental splenosis was produced in normal rodents and in
      animals following splenectomy. Splenosis was more in splenectomised than in
      normal animals. In the present study, in animals into whom splenic fragments were
      implanted subcutaneously, there were less peritoneal splenic growth areas than in
      controls. The hypothesis is presented that there is a population size feedback
      control regulatory mechanism operating in splenic growth and regeneration. If
      such regulators are present in the circulation, administration of normal plasma
      should inhibit splenosis and this may serve as a model to isolate such
      regulators. This was not the case in these experiments.

PMID- 18084863
TI  - An overview of the safety and efficacy of a novel, natural(-)-hydroxycitric acid
      extract (HCA-SX) for weight management.
AB  - Garcinia cambogia-derived (-)-hydroxycitric acid (HCA) is a safe, natural
      supplement for weight management. HCA is a competitive inhibitor of ATP citrate
      lyase, a key enzyme which facilitates the synthesis of fatty acids, cholesterol
      and triglycerides. Previous studies in our laboratories have demonstrated the
      superior bioavailability of a novel calcium-potassium salt of HCA derived from
      Garcinia cambogia (HCA-SX, Super CitriMax). Greater bioavailability of HCA-SX was
      observed when taken on an empty stomach. HCA-SX was also shown to exhibit
      concentration-dependent release of serotonin in isolated rat brain cortex, which
      may explain its appetite suppressive action. Acute oral, acute dermal, primary
      dermal irritation, primary eye irritation and 90-day chronic toxicity studies, as
      well as Ames bacterial reverse mutation and mouse lymphoma tests, were assessed
      to determine the safety of HCA-SX. In the 90-day toxicity study, dose- and time
      dependent effects of HCA-SX were assessed on body weight, selected organ weights,
      hepatic and testicular lipid peroxidation and DNA fragmentation, hematology and
      clinical chemistry, and histopathology in male and female Sprague-Dawley rats. No
      remarkable toxicity results were detected, demonstrating the safety of HCA-SX.
      Furthermore, clinical studies to evaluate the safety and efficacy of HCA-SX over
      a period of eight weeks were conducted in 60 human volunteers. Subjects were
      given a 2,000 kcal diet/day, participated in a 30 min walking exercise program 5
      days/week and given an oral dose of placebo or 4666.7 mg HCA-SX (providing 2,800
      mg HCA) in three equally divided doses 30-60 min before meals, Body weight, BMI,
      lipid profiles, serum leptin, serotonin and excretion of urinary fat metabolites
      were determined at 0, 4 and 8 weeks of treatment. At the end of 8 weeks, body
      weight and BMI decreased by 5.4% and 5.2%, respectively. Food intake, total
      cholesterol, LDL, triglycerides and serum leptin levels were significantly
      reduced, while HDL and serotonin levels, and excretion of urinary fat metabolites
      (a biomarker of fat oxidation) significantly increased. No significant adverse
      effects were reported. These results demonstrate the safety, bioavailability and
      efficacy of HCA-SX in weight management.

PMID- 18084864
TI  - Flow-injection EPR investigation on OH radical scavenging activity of Gd(III)
      containing MRI contrast media.
AB  - The OH radical scavenging activity of a series of Gd(III) MRI contrast media,
      such as Gd(III)DTPA, Gd(III)BMA and Gd(III)DO3A, were evaluated by means of EPR
      spin trapping measurements. The second order reaction rate constant (k2)
      occurring between Gd(III)DTPA and OH radical was estimated to be 3.26 x 10(10)
      (M(-1)s(-1)), which was ten times larger than that of the free ligand DTPA (3.86
      x 10(9) M(-1)s(-1). The k2 values of Gd(III)BMA and Gd(III)DO3A were also
      determined to be 1.31 x 10(10) and 1.77 x 10(10) (M(-1)s(1)), respectively. The
      present results suggest that widely used Gd(III) containing MRI reagent exhibit
      OH radical scavenging activity, and these values of k2 are same order as that of
      ascorbic acid (1.16 x 10(10) M(-1)s(-1)) which has been well established to be
      the most powerful OH radical scavenger. Based on the EPR measurements performed
      for these Gd(III) complexes, a possible reaction mechanism of the OH radical
      scavenging action of these MRI contrast media will be discussed.

PMID- 18084865
TI  - Elevated plasma leptin levels associated with high blood pressure and TG rich
      lipoproteins but not associated with plasma gonadotropins, estradiol and cortisol
      levels in peri- and postmenopausal lean women with undefined symptoms.
AB  - We evaluated associations of leptin with blood pressure, plasma lipid metabolism,
      and endocrine status in 140 perimenopausal Japanese women. In this study, the
      mean plasma leptin level is 8.6 +/- 4.8 ng/ml and the range is 1.7 to 29.6 ng/ml.
      There were significant correlations between plasma leptin concentration and
      systolic blood pressure (r +/- 0.647, p < 0.0001) and diastolic blood pressure (r
      = 0.242, p = 0.0043). We observed significant correlation of plasma leptin
      concentration and LDL-cholesterol, triglyceride concentrations. However, no
      significant differences were observed in the correlation of plasma leptin and LH,
      FSH, estradiol and cortisol concentrations. In conclusion, leptin showed a
      significant association with blood pressure and lipid metabolism. It is suggested
      that leptin may play an important role in physiological regulation of sympathetic
      nervous system and lipid metabolism in peri-and postmenopausal women.

PMID- 18084866
TI  - Studies on the radioprotective effect of etiocholanolone.
AB  - One-hundred forty male mice of an inbred strain (C3H/St) were divided into four
      groups of thirty-five each and were given total body irradiation of 750 cGy.
      After X-irradiation, one group was given etiocholanolone alone, the other was
      given bone marrow alone, a third was given both of these. One group was used as a
      control and was given no treatment after irradiation. The bone marrow used was
      obtained from the same inbred strain of mice. The most remarkable hematologic
      recovery was seen in the group which was given both etiocholanolone and bone
      marrow. The groups given only etiocholanolone or only bone marrow recovered
      better than the control group. Overall survival was best for the group receiving
      both modes of treatment and worst for the control group. Survival for the groups
      receiving a single mode of treatment lay in between the other two mentioned
      above.

PMID- 18084867
TI  - 3D conformal hepatic radiation therapy for metastatic colorectal cancer.
AB  - One patient with a large metastatic liver lesion from colorectal cancer treated
      with 3DCHRT was reported along with review of literature. 3DCHRT is an effective
      palliative treatment and can achieve prolongation of life with improved quality
      and can control the liver pain and prevent possible liver failure.

PMID- 18084868
TI  - Diagnosing cystic fibrosis--asthma and failure to thrive as indications for a
      sweat test.
AB  - Children with asthma or failure to thrive (FTT) are frequently referred for the
      quantitative pilocarpine iontophoresis sweat test (QPIT) for diagnosing cystic
      fibrosis (CF). The aim of our study was to compare the prevalences of asthma and
      FTT among patients with a confirmed diagnosis of CF. Two-hundred and fifty-five
      children, who were referred for QPIT between 1991-1996 in order to rule out CF
      were studied retrospectively. All sweat samples had been obtained and analyzed
      according to the National Committee For Clinical Laboratory Standards. Asthma was
      defined as 24 episodes of wheezing, treated successfully by inhaled
      bronchodilators. Failure to thrive was was defined by either a weight below the
      5th precentile or crossing of 2 major precentiles in 1 year. The prevalence of
      asthma was significantly higher than that of FTT among the cohort study (28.6%
      vs. 7.1% as a single indication, and 36.5% vs. 7.9% when combined with other
      indications). The prevalence of CF among patients with FTT was higher than among
      asthmatic patients (5.2% vs. 3%, p = 0.06). Not one patient diagnosed as having
      CF was referred to a sweat test only because of asthma. As a single presentation,
      the diagnostic yield of asthma seems to be poor, compared to FTT. However,
      further, larger-scale studies should be conducted on this issue.

PMID- 18084869
TI  - Supraglottic devices: a possible role in prehospital toxic mass casualty event?
AB  - Rapidly progressive respiratory failure is the leading cause of death from
      inhalation of toxic chemical warfare agents. In an expected chaotic scenario,
      direct laryngoscopic tracheal intubation is unlikely to be easily and quickly
      performed due to shortage of medical personnel experienced with laryngoscopy
      and/or reduced dexterity imposed by the protective gear worn by the caregivers.
      Supraglottic devices have increasingly been used for emergent airway control in
      prehospital settings, thus avoiding the need for laryngoscopy. This review
      summarizes Medline English literature search on supraglottic devices and their
      use in the prehospital setting or in mass casualty event focusing on their
      potential role for emergent airway control in the setup of toxic inhalation.

PMID- 18084870
TI  - X-ray fluorescence measurement of bone calcium, phosphorous and fluoride in a rat
      osteoporosis model.
AB  - The fluoride (F), calcium (Ca) and phosphorous (P) content in two parts of the
      bone mandible, lumbar spine and femur of rats fed a low mineral diet and
      corresponding controls were determined by X-ray fluorescence. The anterior part
      of the mandible, including teeth was labeled as part I while the posterior part,
      including the mandibular head but excluding the teeth was designed as part II.
      The bone Ca, P and F content of part I was the same for the experimental and
      control groups. The Ca, P and F content of part II was decreased in the low
      mineral diet group (p < 0.01). The values for F were considerably lower than in
      the controls. The lumbar spine and femur were used as whole bones and showed a
      significantly lower values for the three elements measured in the experimental
      group (p < 0.01). Stress or other stimuli from mandibular movement and occlusal
      force may be involved in preventing bone density decline, while density loss
      could be a result of lower physical stimulation, which may exert a greater effect
      than the level of fluoride in bones. It is possible that the absence of
      significant difference in fluoride levels in part I of the mandible may have been
      caused by its accumulation in teeth.

PMID- 18084871
TI  - Hyponatremia secondary to multiple etiologies: a case report.
AB  - We herein describe a rare case of hyponatremia that was aggravated by a burn
      injury. The patient was also found to have hypothyroidism, followed by SIADH, and
      finally CSWS, which showed complicated clinical features. A 68-year-old man was
      admitted for evaluation and treatment of a thermal burn. On admission, the
      patient was dehydrated, which was evidenced by physical signs. The patient had
      hyponatremia (serum Na 123 mmol/L) with high excretion of urinary sodium. Plasma
      AVP levels related to plasma osmolality were high. Plasma levels of renin and
      aldosterone were low, while the plasma ANP level was normal. However, there was
      no deficiency of mineralocorticoid or glucocorticoid. After admission, the
      hyponatremia worsened, and edema with hypoproteinemia developed. The patient was
      found to have hypothyroidism due to chronic thyroiditis. However, hyponatremia
      was not completely recovered with replacement of thyroid hormone. The
      hyponatremia was normalized by administration of DMC. The skin injury was treated
      with a skin graft. After DMC was discontinued, hyponatremia developed once again.
      However, this time, there was no inappropriate antidiuresis and the hyponatremia
      was normalized with the administration of fludrocortisone. These findings
      revealed that the hyponatremia in this patient may have been primarily due to
      CSWS. It was most likely exacerbated by hypothyroidism, burn injury, and SIADH
      caused by the infection. The patient showed physical signs of dehydration and
      edema. Furthermore, biochemical laboratory data were unable to distinguish
      between hypovolemia and non-hypovolemia. These complicated features were
      explained by multiple disorders

PMID- 18084872
TI  - An early evaluation of malignant tendency with plectin expression in human
      colorectal adenoma and adenocarcinoma.
AB  - Tumor cells are morphologically different from normal cells. In this situation,
      we proposed that plectin, one of the intermediate filament associated proteins,
      might play some special roles in the tumorigenesis. Plectin exhibits a wide
      distribution spectrum among various tissues; however, it is scarcely investigated
      in tumor tissues including colorectal adenocarcinoma. In this study, we searched
      the plectin expression in 25 cases of colorectal adenocarcinoma and 10 cases of
      tubular adenoma with focal adenocarcinoma by immunohistochemical method. The
      results reveal that plectin is up-regulated in colorectal adenocarcinoma as well
      as in bizarre glands and locally invasive tumor nests in tubular adenoma,
      compared with normal colorectal mucosa. Over-expression of plectin in locally
      invasive tumor nests might help us in diagnosis of distinguish microinvasive foci
      from normal glands. The bizarre glands in adenoma might be precancerous lesions
      since the expression of plectin in them was identical to that of adenocarcinoma
      but in contrast to that of normal glands. The overexpression of plectin might
      affect the organization of cytoskeleton, which might further cause tumorigenesis
      and morphological change of colorectal epithelial cells.

PMID- 18084873
TI  - Evaluation of double-blind comparison of fluvoxamine and paroxetine in the
      treatment of depressed outpatients in menopause transition.
AB  - To evaluate the efficacy of the selective serotonin reuptake inhibitors (SSRIs)
      fluvoxamine and paroxetine in treating depression in the menopausal transition
      and to compare their efficacy, safety, side-effect profiles and drug compliance.
      One hundred and five perimenopausal patients (51.3 +/- 2.5 yr of age) were
      randomly assigned to receive a dosage of 50 mg/day of fluvoxamine (n=53) or 20
      mg/day of paroxetine (n=52). The visual analog scale (VAS), Hamilton Rating Scale
      for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) scores were
      evaluated before and after 3 months of therapy in the two groups of women.
      Significant reduction in HAM-D and HAM-A scores was observed in both groups of
      women, without significant difference between the two groups. VAS score in the
      fluvoxamine group (-62.6 +/- 5.2%) was significantly lower than that in the
      paroxetine group (-51.1 +/- 4.3%) (P < 0.0001). Although fluvoxamine compares
      favourably with paroxetine in rate of reduction of VAS score, this study suggests
      that both SSRIs are effective for and tolerated in depressed perimenopausal
      outpatients.

PMID- 18084874
TI  - The effect of physicians' advice and recommendations on the compliance with
      hormone replacement therapy in the treatment of postmenopausal symptoms in
      Japanese women--a prospective study.
AB  - A retrospective study was performed to determine the compliance of hormone
      replacement therapy (HRT), the reason for discontinuation. This study comprised
      477 postmenopausal women who attended the women's psychosomatic and menopause
      clinic between January 1991 and December 2002. For the purposes of analysis, the
      women were classified into two groups. In Group A (242 subjects), subjects were
      allowed to decide whether or not to suspend or discontinue the drug, taking their
      condition into account, after their symptoms were alleviated. In Group B (235
      subjects), all the women were informed as to the drug's excellent effects on
      osteoporosis and skin tissue before HRT was started and after their symptoms were
      alleviated. In Group A, the percentage of women who were still on this therapy
      was 77.7%, 34.3%, 21.1% and 8.7% at 3, 6, 12 and 24 months respectively after the
      start of therapy. Alternatively, in group B, the 24-month continuation rate was
      more than 50%. At 36 months (47.2%) and 60 months (38.7%) continuation rates were
      also significantly higher than those in group A (P < 0.0001). The leading reasons
      in the women's decision to discontinue HRT were improvement of symptoms (68.0%
      and 77.8% in group A and B, respectively, p = 0.408). The incidence in the
      women's decision to discontinue HRT by the reason of fear of cancer was
      significantly higher in group A (10.8%) than in group B (2.8%) (P = 0.008). In
      this study, the key factor affecting HRT compliance proved to be physician's
      advice. This means that when HRT is administered to Japanese women with the
      objective of alleviating menopausal symptoms and, high compliance can be expected
      provided individual patients are allowed to decide for themselves when HRT should
      begin end.

PMID- 18084875
TI  - Altered synemin could affect the organization of intermediate filament in human
      hepatocellular carcinoma.
AB  - Cells of human hepatocellular carcinoma (HCC) were morphologically different from
      those of normal liver. Intermediate filaments are important in building the
      architecture of liver cells and are proposed to interact with other cellular
      components. Synemin is one of intermediate filament associated proteins which can
      link between intermediate filament and other cytoskeletal structures. It was
      suggested that synemin might play some roles in tumorigenesis of hepatocellular
      cancinoma. In this study, we searched the synemin expression in 18 human HCCs by
      immunohistochemistry. The results revealed that synemin was modulated nearly in
      all human HCC cases. Many 0.4-0.8 microm-thick bundles were found in the IF
      extracts of liver and HCCs. These bundles were greater in diameter about 40 to 80
      times of single IF. We speculated that the IFs were organized into the "filament
      bundles" to support the normal shape of the cells. That was, normal cell needed
      numerous synemin to lock the individual IF into stable "filament bundles". In
      cancer cells, the synemin was altered and this might lead to a loosened change of
      filament bundles, and the cancer cells would become pleomorphic.

PMID- 18084876
TI  - Leptospirosis presenting as acute pancreatitis and cholecystitis.
AB  - We report a rare case of a 21-year-old man with leptospirosis mimicking acute
      pancreatitis and cholecystitis. This case report aims at pointing out the need of
      taking into consideration the possibility of leptospirosis in patients with an
      influenza-like syndrome, headache accompanied by acute abdominal pain and a
      suspicious exposure in order to prevent unnecessary surgical interventions.

PMID- 18084877
TI  - Evaluation of myocardial sympathetic nerve function in patients with mitral valve
      prolapse using iodine-123-metaiodobenzylguanidine myocardial scintigraphy.
AB  - Mitral valve prolapse (MVP) is closely related to myocardial sympathetic nerve
      function. This study evaluated the presence of impaired myocardial sympathetic
      nerve function by Iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in ten
      patients with MVP. For comparison, 15 healthy subjects without heart disease were
      investigated (control group). Single photon emission computed tomography (SPECT)
      and anterior planar myocardial scintigraphy were performed 15 min (initial
      images) and 3 hours (delayed images) after injection of MIBG (111 MBq). The
      location and degrees of reduced tracer uptake were evaluated. Myocardial MIBG
      uptake was quantified by uptake ratio of the heart (H) to upper mediastinum (M)
      on the anterior planar images (H/M). Percentage washout of MIBG in nine sectors
      of all oblique slices along the short-axis was calculated. The washout rates were
      higher at the inferoposterior and septal segments in patients with anterior
      leaflet prolapse, and at inferoposterior and lateral segments in patients with
      posterior leaflet prolapse. The bull's eye map showed increased washout rate in
      the apical and posteroseptal basal segments. There was no significant difference
      in the H/M ratio between MVP patients and the control group. These results
      indicate that MIBG can be used to evaluate localized myocardial sympathetic nerve
      function in MVP.

PMID- 18084878
TI  - New approaches to the treatment of AIDS with special reference to overcoming
      interferon resistance.
AB  - This is a brief review on studies of attacking HIV through a new angle. In
      previous studies, we have found that many patients with AIDS are resistant to
      interferon (IFN) therapy, and some develop resistance during therapy. Four
      factors were found to be responsible for the resistance of untreated patients:
      (a). release of free-circulating IFN-alpha/beta type 1 receptors, (b). a newly
      detected IFN inhibitory protein, (c). high prostaglandin E2, and (d). high levels
      of cAMP phosphodiesterases, particularly in AIDS-related neoplasms. This may
      interfere with intrinsic disease resistance and with the efficacy of IFN therapy.
      In an attempt to overcome this resistance, new compounds were synthesized which
      increase endogenous production of alpha, beta and gamma IFNs, have anti-template
      activity against DNA and RNA polymerases, inhibit reverse transcriptases and
      activates IFN-induced double-stranded RNA (dsRNA)-dependent protein kinase. It is
      expected that planned nonhuman primate and clinical studies will support
      preliminary findings. Preliminary in vitro and animal studies suggest that these
      new compounds may be effective against HIV, including multi-drug resistant
      strains.

PMID- 18084879
TI  - Are there any ethnic differences in the number of coronary artery bypass and
      valve heart surgeries among Caucasians, African Americans and Puerto Ricans? The
      western New York experience.
AB  - Prevalence rates of coronary artery bypass and valve surgery among Hispanics has
      not been well documented, particularly with regards to Puerto Ricans.
      Accordingly, we conducted a retrospective review of the surgical database in the
      Greater Buffalo Area of Western New York, serving a large Puerto Rican Hispanic
      community between January 1, 2001 and June 30, 2001, in order to determine if
      there is a particular trend in the utilization of these two surgical procedures
      among Caucasians, African Americans and Puerto Ricans. The results of this brief
      report shows that 95% of these surgical interventions, in the above mentioned
      time period, were done in Caucasians; while only 4.2% of these combined surgeries
      were performed in African Americans and in only 0.8% of Puerto Rican Hispanics.
      These results add to the growing evidence supporting lack of appropriate tool(s)
      or mechanism(s) to address health care issues among minorities, particularly
      Hispanic Puerto Ricans. This is the first report of this kind showing rates of
      coronary artery bypass and valve surgery involving this particular sector of the
      Hispanic community in the United States. It also emphasizes the need to promptly
      identify these deficiencies, particularly when considering that Hispanics are the
      most rapidly increasing minority ethnic population in the United States.

PMID- 18084880
TI  - Mitral valve contour in short axis: a useful view in the diagnosis of mitral
      valve prolapse.
AB  - The diagnosis of mitral valve prolapse still remains a challenging proposition in
      some patients, particularly when the superior and posterior displacement of the
      mitral valve leaflets across the plane of the mitral valve annulus into the left
      atrium during systole is questionable. Therefore, additional reliable and
      reproducible echocardiographic criteria to improve the accuracy of mitral valve
      prolapse diagnosis would be ideal. In this small study, we proposed to assess the
      relationship between the systolic and diastolic contour of the mitral valve, as
      seen from the short axis views of the left ventricle, and compared to the
      currently used standard parasternal long axis view criteria. The apical views and
      the M-mode of the mitral valve were also assessed. From a total of 70
      transthoracic echocardiograms that were prospectively examined, 50
      echocardiograms were included for analysis. Nine patients met criteria for mitral
      valve prolapse using the parasternal long axis views standard definition.
      However, in these patients the concordance using M-mode and apical view criteria
      was 56% and 33%, respectively. None of the patients met M-mode criteria for
      mitral valve prolapse if the parasternal long axis criteria was not present,
      however 5 patients showed apical view mitral valve prolapse without meeting
      parasternal long axis views criteria. Conversely, a 100% concordance was noted
      between the parasternal long axis criteria for mitral valve prolapse and the
      contour of the mitral valve as seen from the short axis views. In all 9 patients
      with mitral valve prolapse, using the parasternal long axis criteria, a prominent
      buckling of the mitral valve was noted from the short axis views. Moreover, none
      of the 41 patients without mitral valve prolapse showed buckling in the short
      axis views. Therefore, buckling of the mitral valve, as seen from the short axis
      views, appears to provide a confirmatory role in diagnosing mitral valve
      prolapse, particularly in questionable cases; improving the overall accuracy.
      These findings should be validated in a double blind prospective study.

PMID- 18084881
TI  - Gene expression profiles of late colonic Crohn's disease.
AB  - To determine the genetic program mediating and maintaining the change from
      susceptibility to Crohn's disease (CD) to ongoing tissue destruction and loss of
      function, we utilized Affymetrix HG U95 AV2 Gene Chips and analyzed unpooled
      surgical CD colon specimens from adult patients. Using the patient as his own
      genetic filter we examined involved versus uninvolved adjacent areas, comparing
      results within one individual and then performing analysis comparing results
      between four individuals. Our results interrogated twice as many genes than the
      previous studies that used pooled unmatched specimens. We identified a limited
      set of nine genes upregulated in all four patients, and one gene (PTN) as
      downregulated. Several of the genes, including DEFA6, PAP, REG1A, REG1B, and
      phospholipase A2 had been implicated in previous studies, supporting their key
      role in CD. In 3 of 4 patients, 24 genes were upregulated in diseased areas,
      including DEFA5, IL-8, MMP-1, S100 calcium binding protein, and MGSA. Additional
      new candidate genes were identified, including DMT1, SERPINA1, GW112, and iNOS.
      The use of the unpooled samples allowed the detection of significant
      interindividual differences in expression of many other genes, supporting disease
      heterogeneity in CD. Results with select genes were confirmed with RT-PCR
      studies, as well as on biopsy samples from pediatric patients. We have determined
      a common profile of "late" CD, and also demonstrated the potential variability,
      suggesting possible differences in etiology, triggers, and the need for more
      individualized management. Additional studies to investigate protein expression
      of these candidate genes should be undertaken.

PMID- 18084882
TI  - A gastric hiatal hernia may make abdominal pain disappear.
AB  - Recurrent abdominal pain developed in a 74-year-old woman that chronically
      suffered from retrosternal pain and regurgitation. An erect abdominal plain film
      showed a fluid level in the ascending colon and an enlargement of the posterior
      lower mediastinum containing gas on the right. Unexpectedly, the patient reported
      that abdominal pain disappeared after meals. Double contrast enema and
      contemporaneous barium swallow showed herniation of the left colonic flexure into
      the left lower mediastinum and a gastric hernia within the right lower
      mediastinum, respectively. The hernias were in the same site of the enlargement
      of the mediastinum seen on the plain abdominal film. The colonic hernia partially
      reduced when the gastric hernia was filled with barium. We postulate that these
      findings could explain the disappearance of the colic obstruction and abdominal
      pain after meals.

PMID- 18084884
TI  - Breast cancer in intraductal carcinogen-treated non-human primates.
AB  - Eight female Macaca arctoides monkeys were given dimethylbenzanthracene (DMBA)
      directly into the milk ducts. During a 4-year observation period, ending with
      euthanasia and autopsy, no mammary cancers were noticed. However, one animal
      developed a superficial localized squamous cell carcinoma. DMBA is highly
      carcinogenic in rodents, e.g. producing a high incidence of breast cancer in C3H
      mice. It was concluded that carcinogenicity testing should be extended beyond
      testing in rodents to non-human primates in order to distinguish "primary rodent
      carcinogens" from those highly active in primates as well. Studies are in
      progress to study carcinogens in human cell lines transplanted into nu/nu mice.

PMID- 18084883
TI  - Multiple medical problems following agent orange exposure.
AB  - A patient exposed to agent orange and a gunshot wound during the Vietnam War has
      developed multiple medical problems including nocardiosis, onychomycosis
      (Trichophyton rubrum), multiple thromboembolic episodes, hemochromatosis,
      diabetes mellitus type 2, diabetic neuropathy, activated protein C resistance
      (without Leyden V 1st mutation), degree A-V block, lung cancer (metastatic
      adenocarcinoma), carpal tunnel syndrome and arthritis.

PMID- 18084885
TI  - YABA virus induced tumor in men--long term follow-up and possible bio-warfare
      role.

PMID- 18084886
TI  - Adequate reduction degree of pituitary gonadotropin levels in the clinical
      management of short-term hormone replacement therapy of women with menopausal
      symptoms.
AB  - The purpose of this study was to clarify the adequate reduction rate of pituitary
      gonadotropins in ideal clinical management of shortterm hormone replacement
      therapy (ST-HRT) in postmenopausal women with undefined symptoms. Subjects
      included a total 324 postmenopausal patients between 48 and 61 years of age who
      visited the Department of Obstetrics and Gynecology at Osaka Medical College
      Hospital for the consult of menopausal symptoms. Administration of conjugated
      equine estrogen (0.625 mg/day) and progestin (2.5 mg/day) in the patients for 8
      weeks. HRT was markedly effective in 28.7% of cases, effective in 40.7%, fairly
      effective in 21.9%, and ineffective in 8.6% of cases. The plasma concentration of
      FSH and LH after administration decreased significantly (P < 0.001) by 58.1% and
      59.9% for markedly effective cases, and by 31.0% and 36.1% for effective cases.
      On the other hand, decreases in FSH and LH concentration were 14.1% and 1.3% for
      the fairly effective and 8.5% and -5.1% for ineffective cases, demonstrating a
      significantly greater decrease in plasma FSH and LH levels in the markedly
      effective and effective cases than those in ineffective cases (P < 0.001). There
      were significant differences in the reduction rates of plasma FSH and LH levels
      between in cases showing (59.9% and 53.2%) and not showing the side effects
      (24.8% and 25.9%), respectively (P < 0.0001). In conclusion, efficacy of ST-HRT
      was significantly correlated to the degree of decrease in plasma FSH and LH
      levels in patients with undefined symptoms. In addition, efficacy appeared to be
      correlated to the incidence of side effects. The degree of reduction of FSH (24.8
      31.0%) and LH (25.9-36.1%) from the baseline may possibly be used as the suitable
      therapeutic window for hormone levels during HRT. The present results suggest
      that plasma gonadotropin levels could be a useful indicator for the management of
      patients undergoing short-term HRT for women with menopausal symptoms.

PMID- 18084887
TI  - Introduction. History of the peroxiredoxins and topical perspectives.
AB  - We have surveyed the early biochemical, structural and enzymatic studies on the
      peroxiredoxin family, within the broad context of the other chapters included
      within this book. Both the antioxidant defence and peroxide-linked cell
      signalling roles of the peroxiredoxins are introduced. The possible membrane
      association of certain peroxiredoxins is assessed and the structural
      characterization of the peroxiredoxins by electron microscopy is given some
      emphasis here. The important contribution of X-ray crystallographic studies to
      the understanding of peroxiredoxin structure is given due attention. Finally,
      some medical perpectives are introduced, with emphasis upon the understanding of
      the microbial peroxiredoxins as possible future drug targets.

PMID- 18084888
TI  - Evolution of the peroxiredoxins.
AB  - Peroxiredoxins compose a superfamily of peroxidases ubiquitously found throughout
      evolution in prokaryotes, archaea and eukaryotes. These enzymes contain a
      conserved catalytic peroxidatic cysteine (Cp) in the N-terminal region of the
      protein. The residues surrounding Cp and the catalytic site appear also to be
      well conserved. Peroxiredoxins can be classified either into three subfamilies
      according to their catalytic mechanism or into five subfamilies according to
      sequence homology. Notably, the number of peroxiredoxin genes increased during
      evolution. In eukaryotes, the higher number of genes coding for peroxiredoxin
      family members is due to the existence of different isoforms targeted to
      different subcellular compartments but is probably due also to the acquisition of
      new functions. Indeed, it has been postulated that the antioxidant protective
      role of peroxiredoxins, which is particularly critical in prokaryotes, in yeasts
      and in parasitic eukaryotes, may have evolved to a modulatory role in hydrogen
      peroxide signaling in plants and animals.

PMID- 18084889
TI  - Structural survey of the peroxiredoxins.
AB  - Peroxiredoxins (Prxs) are ubiquitous proteins that use an active site Cys residue
      to reduce hydroperoxides. Structural studies since the first Prx structure was
      determined in 1998 have produced 35 crystal structures of wild type and mutant
      Prxs with at least one representative structure from each of the five major
      evolutionary subfamilies of Prxs. These structures have yielded a great deal of
      knowledge about Prx structure and structure-function relations, revealing
      fascinating variations in quaternary structure and details of the fully-folded
      and locally-unfolded conformations that are involved in the catalytic cycle of
      all Prxs.

PMID- 18084890
TI  - The catalytic mechanism of peroxiredoxins.
AB  - Peroxiredoxins carry out the efficient reduction of a typically broad range of
      peroxide substrates through an absolutely conserved, activated cysteine residue
      within a highly conserved active site pocket structure. Though details of
      reductive recycling after cysteine sulfenic acid formation at the active site
      vary among members of different Prx classes, local unfolding around the active
      site cysteine is likely generally required in these proteins for disulfide bond
      formation with a second resolving cysteine and/or for access of the reductant to
      the oxidized active site. The conformational change associated with the catalytic
      cycle and the redox-dependent decamer formation occurring in at least some
      typical 2-Cys Prxs have interesting implications in the interplay between active
      site loop dynamics, oligomerization state, catalytic efficiency and propensity
      toward inactivation during turnover in these important antioxidant enzymes.

PMID- 18084891
TI  - Kinetics of peroxiredoxins and their role in the decomposition of peroxynitrite.
AB  - Methodologies and results of studies on the kinetics of peroxiredoxins (Prx) are
      reviewed. Peroxiredoxins are broad-spectrum peroxidases that catalyze the
      reduction of H2O2, organic hydroperoxides and peroxynitrite by thiols. Their
      catalytic cycle starts with the oxidation of a particularly reactive cysteine
      residue (C(P)) to a sulfenic acid derivative by the peroxide substrate, the
      sulfenic acid then reacts with a thiol to form a disulfide, and the cycle is
      completed by thiol/disulfide exchange reactions that regenerate the ground-state
      enzyme. Depending on the subtype of peroxiredoxin, the thiol reacting with the
      primary oxidation product (E-SOH) may be a cysteine residue of a second subunit
      (typical 2-Cys Prx), a cysteine residue of the same subunit (atypical 2-Cys Prx)
      or reducing substrate (1-Cys Prx and at least one example of an atypical 2-Cys
      Prx). In a typical 2-Cys Prx the intra-subunit disulfide formation with the
      second "resolving" cysteine (C(R)) is mandatory for the reduction by the specific
      substrate, which is a protein characterized by a CXXC motif such as thioredoxin,
      tryparedoxin or AhpF. These consecutive redox reactions define the catalysis as
      an enzyme substitution mechanism, which is corroborated by a ping-pong pattern
      that is commonly observed in steady-state analyses, chemical identification of
      catalytic intermediates and stopped-flow analyses of partial reactions. More
      complex kinetic patterns are discussed in terms of cooperativity between the
      subunits of the oligomeric enzymes, generation of different oxidized
      intermediates or partial over-oxidation of C(P) to a sulfinic acid. Saturation
      kinetics is often not observed indicating that a typical complex between reduced
      enzyme and hydroperoxide is not formed and that, in these cases, formation of the
      complex between the oxidized enzyme and its reducing substrate is slower than the
      reaction within this complex. Working with sulphur catalysis, Prxs are usually
      less efficient than the heme- or selenium-containing peroxidases, but in some
      cases the k(+1) values (bimolecular rate constant for oxidation of reduced E by
      ROOH) are comparable, the overall range being 2 x 10(3)-4 x 10(7) M(-1)s(-1)
      depending on the hydroperoxide and the individual Prx. For the reduction of
      peroxynitrite k(+1) values of 1 x 10(6) up to 7 x 10(7) M(-1)s(-1) have been
      measured. The net forward rate constants k'(+2) for the reductive part of the
      cycle range between 2 x 10(4)-1 x 10(7) M(-1)s(-1). These kinetic characteristics
      qualify the peroxiredoxins as moderately efficient devices to detoxify
      hydroperoxides, which is pivotal to organisms devoid of more efficient
      peroxidases, and as most relevant to the detoxification of peroxynitrite. In
      higher organisms, their specific role is seen in the regulation of signalling
      cascades that are modulated by H2O2, lipid hydroperoxides or peroxynitrite.

PMID- 18084892
TI  - The peroxiredoxin repair proteins.
AB  - Sulfiredoxin and sestrin are cysteine sulfinic acid reductases that selectively
      reduce or repair the hyperoxidized forms of typical 2-Cys peroxiredoxins within
      eukaryotes. As such these enzymes play key roles in the modulation of peroxide
      mediated cell signaling and cellular defense mechanisms. The unique structure of
      sulfiredoxin facilitates access to the peroxiredoxin active site and novel sulfur
      chemistry.

PMID- 18084893
TI  - Peroxiredoxins in bacterial antioxidant defense.
AB  - Peroxiredoxins constitute an important component of the bacterial defense against
      toxic peroxides. These enzymes use reactive cysteine thiols to reduce peroxides
      with electrons ultimately derived from reduced pyridine dinucleotides. Studies
      examining the regulation and physiological roles of AhpC, Tpx, Ohr and OsmC
      reveal the multilayered nature of bacterial peroxide defense. AhpC is localized
      in the cytoplasm and has a wide substrate range that includes H2O2, organic
      peroxides and peroxynitrite. This enzyme functions in both the control of
      endogenous peroxides, as well as in the inducible defense response to exogenous
      peroxides or general stresses. Ohr, OsmC and Tpx are organic peroxide specific.
      Tpx is localized to the periplasm and can be involved in either constitutive
      peroxide defense or participate in oxidative stress inducible responses depending
      on the organism. Ohr is an organic peroxide specific defense system that is under
      the control of the organic peroxide sensing repressor OhrR. In some organisms Ohr
      homologs are regulated in response to general stress. Clear evidence indicates
      that AhpC, Tpx and Ohr are involved in virulence. The role of OsmC is less clear.
      Regulation of OsmC expression is not oxidative stress inducible, but is
      controlled by multiple general stress responsive regulators.

PMID- 18084894
TI  - The NADH oxidase-Prx system in Amphibacillus xylanus.
AB  - Amphibacillus NADH oxidase belongs to a growing new family of peroxiredoxin
      linked oxidoreductases including alkyl hydroperoxide reductase F (AhpF). Like
      AhpF it displays extremely high hydroperoxide reductase activity in the presence
      of a Prx, thus making up the NADH oxidase-Prx system. The NADH oxidase primarily
      catalyzes the reduction of oxygen by NADH to form H2O2, while the Prx immediately
      reduces H2O2 (or ROOH) to water (or ROH). Consequently, the NADH oxidase-Prx
      system catalyzes the reduction of both oxygen and hydrogen peroxide to water with
      NADH as the preferred electron donor. The NADH oxidase-Prx system is widely
      distributed in aerobically growing bacteria lacking a respiratory chain and
      catalase, and plays an important role not only in scavenging hydroperoxides but
      also in regenerating NAD in these bacteria.

PMID- 18084895
TI  - Peroxiredoxin systems in mycobacteria.
AB  - Like other actinomycetes Mycobacterium tuberculosis lacks glutathione and,
      consequently, the glutathione peroxidases that dominate the antioxidant defence
      of its mammalian hosts. The hydrogen peroxide metabolism of the pathogen has for
      long been recognised to depend on a heme-containing catalase/peroxidase. Clinical
      isolates lacking the catalase were virulent and proved to be resistant to the
      first line tuberculostatic isoniazid, because the enzyme is evidently required to
      activate this drug. The survival and virulence of such strains are attributed to
      the peroxiredoxin-type peroxidases alkyl hydroperoxide reductase (AhpC) and
      thioredoxin peroxidase (TPx). The most common AhpC reductant in bacteria, the
      disulfide reductase AhpF, is deleted in M. tuberculosis. Instead, AhpC can be
      reduced by AhpD, a CXXC-motif-containing protein, or by one of the mycobacterial
      thioredoxins, TrxC. TPx is reduced by thioredoxins B and C. Mycobacteria contain
      three more peroxiredoxins, the 1-Cys-Prx AhpE, Bcp and BcpB, whose function and
      reductants are still unknown.

PMID- 18084896
TI  - Peroxiredoxin systems of protozoal parasites.
AB  - Cellular redox metabolism is considered to be involved in the pathophysiology of
      diseases caused by protozoal parasites such as Toxoplasma, Trypanosoma,
      Leishmania, and Plasmodia. Redox reactions furthermore are thought to play a
      major role in the action of and the resistance to some clinically used
      antiparasitic drugs. Interestingly, in malarial parasites, the antioxidant
      enzymes catalase and glutathione peroxidase are absent which indicates a crucial
      role of the thioredoxin system in redox control. Besides a glutathione peroxidase
      like thioredoxin peroxidase and a glutathione S-transferase with slight
      peroxidase activity, Plasmodium falciparum (the causative agent of tropical
      malaria) possesses four classical peroxiredoxins: Two peroxiredoxins of the
      typical 2-Cys Prx class, one 1-Cys peroxiredoxin with homology to the atypical 2
      Cys Prx class, and a peroxiredoxin of the 1-Cys Prx class have been identified
      and partially characterized In our article we give an introduction to redox-based
      drug development strategies against protozoal parasites and summarize the present
      knowledge on peroxiredoxin systems in Plasmodium.

PMID- 18084897
TI  - The trypanothione system.
AB  - Trypanosomes and Leishmania, the causative agents of severe tropical diseases,
      employ 2-Cys-peroxiredoxins together with cysteine-homologues of glutathione
      peroxidases and ascorbate-dependent peroxidases for the detoxification of
      hydroperoxides. All three types of peroxidases gain their reducing equivalents
      from the parasite-specific dithiol trypanothione [bis(glutathionyl)spermidine].
      Based on their primary structure and cellular localization, the trypanosomatid 2
      Cys-peroxiredoxins are subdivided into two families that occur in the
      mitochondrion and cytosol of the parasites. In Trypanosoma brucei, the cytosolic
      2-Cys-peroxiredoxin, as well as the glutathione peroxidase-type enzyme, is
      essential for cell viability. Despite overlapping substrate specificities and
      subcellular localizations, the two types of peroxidases can obviously not
      substitute for each other which suggests distinct cell-physiological roles.

PMID- 18084898
TI  - Functions of typical 2-Cys peroxiredoxins in yeast.
AB  - Peroxiredoxins are ubiquitous proteins that are found from bacteria to humans.
      Until recently they were thought to solely act as antioxidants catalysing the
      reduction of peroxides through their associated thioredoxin peroxidase activity.
      However, recent work has begun to uncover hitherto unsuspected roles for one
      group of these proteins, the typical 2-Cys peroxiredoxins (2-Cys Prx). For
      example, typical 2-Cys Prxs have been found to have roles in the model organisms
      Schizosaccharomvces pombe and Saccharomyces cerevisiae in regulating signal
      transduction, in DNA damage responses and as molecular chaperones. There is
      increasing evidence that H2O2 is utilised as a signalling molecule to regulate a
      range of important cellular processes. As abundant and ubiquitous peroxidase
      enzymes the peroxidase activity of typical 2-Cys Prxs is important in the
      regulation of these functions. Significantly, studies in yeast suggest that the
      regulation of the thioredoxin peroxidase and chaperone activities of these
      multifunction enzymes is an important aspect of H2O2-mediated signal transduction
      and consequently have provided important insight into the roles of these proteins
      in higher eukaryotes.

PMID- 18084899
TI  - The dual function of plant peroxiredoxins in antioxidant defence and redox
      signaling.
AB  - With 8 to 10 members, the peroxiredoxin gene family of each higher plant with
      known genome sequence is larger than in other eukaryotes. Likewise, the
      complexity of reductive regenerants is very high, e.g. the chloroplast 2-Cys Prx
      is reduced by various thioredoxins, cyclophilin Cyp20-3, the drought induced
      CDSP32 and the NADPH-dependent reductant NTRC. In the light of the apparent
      versatility of the peroxiredoxin system in plants, its specific and important
      functions in antioxidant defence, photosynthesis and stress adaptation, the
      review attempts a survey of present day knowledge on plant peroxiredoxins, their
      biochemical features and transcript regulation, as well as their function in
      photosynthesis, development, stress response and pathogenesis. The emerging
      evidence for plant Prx function in cell signaling is summarized.

PMID- 18084900
TI  - Mitochondrial peroxiredoxins.
AB  - Mitochondria are the major intracellular sites of oxygen consumption producing
      reactive oxygen species (ROS) as toxic by-products of oxidative phosphorylation,
      primarily via electron leakage from the respiratory chain. The resultant types of
      chemical damage to lipids, DNA and proteins are described as well as the broader
      implications for the involvement of ROS in disease onset and progression. The
      relative contributions of mitochondrial, enzyme-linked, antioxidant defence
      systems to tissue protection are also reviewed as is the emerging importance of
      the peroxiredoxin family in general to H2O2-mediated signalling The constituent
      enzymes of the mitochondrial PrxIII pathway are discussed in detail including the
      roles of PrxIII and PrxV in their capacities as typical 2-cys and atypical 2-cys
      thioredoxin-dependent hydroperoxide reductases, respectively. The structures and
      catalytic mechanisms of PrxIII and V are examined and some key properties of the
      reconstituted mitochondrial PrxIII pathway are highlighted with specific
      reference to the susceptibility of peroxiredoxins to inactivation at elevated
      H2O2 levels and their potential for participation in H2O2-mediated signalling
      responses. It is concluded that mitochondrial Prxs form a vital link in an
      integrated cellular antioxidant defence network that minimises ROS-mediated
      damage and ensures that cells mount appropriate responses to increased levels of
      oxidative stress via the upregulation of key cell signalling pathways.

PMID- 18084901
TI  - Peroxiredoxins in the lung with emphasis on peroxiredoxin VI.
AB  - All six mammalian peroxiredoxins are expressed in the lung. Peroxiredoxin (Prx)
      VI is the isoform expressed at the highest level and its lung expression exceeds
      that for other organs. The predominant location of Prx VI is the cytosol and
      acidic organelles of Clara cells of the conducting airways and type II epithelial
      cells and macrophages in the alveoli. Prx I and VI show developmental induction
      of transcription at birth. PrxVI shares structural homology with other
      peroxiredoxins exhibiting a thioredoxin fold and a conserved catalytic Cys
      residue in the N-terminus of the protein. This enzyme is highly inducible by
      oxidative stress in both the neonatal and adult lung consistent with a role in
      antioxidant defense. Prx VI has several properties that distinguish its
      peroxidase activity from other peroxiredoxins: it can reduce phospholipid
      hydroperoxides in addition to other organic hydroperoxides and H2O2; the electron
      donor that serves to reduce the oxidized peroxidatic cysteine is not thioredoxin
      but GSH; instead of homodimerization, heterodimerization with pi-glutathione S
      transferase is required for regeneration of the active enzyme. Prx VI also
      expresses a phospholipase A2 activity that is Ca2+-independent, maximal at acidic
      pH, and dependent on a serine-based catalytic triad and nucleophilic elbow at the
      surface of the protein. Models of altered Prx VI expression at the cellular,
      organ and whole animal levels have demonstrated that Prx VI functions as an
      important anti-oxidant enzyme with levels of protection that exceed those
      ascribed to GSH peroxidase (GPx1). The phospholipase A2 activity plays an
      important role in lung surfactant homeostasis and is responsible for the bulk of
      the degradation of internalized phosphatidylcholine and its resynthesis by the
      reacylation pathway. Expression of peroxiredoxins is elevated in several lung
      diseases including lung cancer, mesothelioma and sarcoidosis, although the
      mechanism for these alterations is not known. The unique properties of Prx VI
      enable it to play an important role in lung cell function.

PMID- 18084902
TI  - Peroxiredoxins in gametogenesis and embryo development.
AB  - Reactive oxygen species have been implicated in gametogenesis and embryo
      development in animals. As peroxiredoxins are now recognized as important
      protective antioxidant enzymes as well as modulators of hydrogen peroxide
      mediated signaling, we addressed here the putative role of this novel family of
      peroxidases in gamete maturation and during embryogenesis in mammals and insects.

PMID- 18084903
TI  - Peroxiredoxins in the central nervous system.
AB  - Oxidative stress is considered one of the causative pathomechanisms of nervous
      system diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic
      lateral sclerosis, stroke and excitotoxicity. The basal expression of six
      different peroxiredoxin (Prx) isozymes show distinct distribution profiles in
      different brain regions and different cell types. PrxI and VI are expressed in
      glial cells but not in neurons; while PrxII, III, IV and V are expressed in
      neurons. Various diseases or models show altered expression levels of these
      isozymes, such as by upregulation of PrxI, II and VI and downregulation of
      PrxIII. Thioredoxin (Trx)I mRNA is distributed widely in the rat brain. This
      distribution pattern may reflect the specific functions of these isozymes.
      Recently, the neuroprotective roles of Prx III and V against ibotenate-induced
      excitotoxicity were reported by two independent groups. Adenovirus transduction
      of PrxIII eliminated protein nitration and prevented gliosis caused by direct
      infusion of ibotenate. Systemic administration of recombinant PrxV diminished
      brain lesions in animals treated with ibotenate. In this chapter, we review the
      causative mechanisms of oxidative stress in neurodegenerative diseases, as well
      as describe the basal and disease-induced changes in Prxs/Trxs/Trx reductases
      expression levels and neuroprotective roles of Trxs and Prxs as demonstrated in
      overexpression models.

PMID- 18084904
TI  - Stress-induced peroxiredoxins.
AB  - Some members of the Prx family are up-regulated in cells under stress conditions.
      Prx I is the major cytoplasmic Prx and is known as a stress-inducible antioxidant
      enzyme. Various stress agents or conditions activate Prx I gene expression in
      vitro and in vivo. The transcription factor Nrf2 and its inhibitor Keap1 play an
      essential role in the regulation of the stress-induced Prx I gene activation
      through the ARE/EpRE (antioxidant/electrophile response element). The expression
      levels of Prx II and III are also up-regulated under stress conditions, although
      the molecular mechanisms of their up-regulation have not yet been thoroughly
      studied. Gene expression of both Prx I and II is activated by X-ray irradiation
      of the testis. Mitochondrial Prx III is up-regulated by stress agents in both
      cultured cells and experimental animals. The up-regulation of the Prxs in cells
      and tissues under oxidative stress conditions is one of the cellular recovery
      responses after oxidative damage.

PMID- 18084905
TI  - Dental pillars of society.
AB  - This special issue of Dental Historian represents an expanded version of a
      lecture given to the annual conference of the Lindsay Society for the History of
      Dentistry in Liverpool on 8 October 2006. It was felt that such a version would
      provide a helpful and informative basis for other researchers interested in these
      important members of the dental profession in the United Kingdom.

PMID- 18084906
TI  - [Toward many academic years].

PMID- 18084907
TI  - [Ongoing medical problems in the anti-doping fight].
AB  - Over the last 20 years systematic doping has become a major threat for elite
      sport. So far, there is no clear information about the daily practice of doping.
      Repeated scandals and recent personal statements have added to our knowledge.
      Several more recent doping agents like Erythropoietin (EPO) and, probably, growth
      hormone (GH) enhance performance in a highly effective way and, together with the
      well known anabolic steroids (AAS), belong to the major doping categories. The
      introduction of EPO has really changed the paradigm in endurance sports allowing
      a good middle class athlete to become a champion. It is evident that doping
      practices are influenced by the possibilities of the anti-doping control system.
      Unethical, criminal medical doctors play a decisive role in the ongoing practice
      of major doping. Apart from the already mentioned substances AAS, EPO and GH
      several novel drugs appear on the horizon. They are highly effective and there is
      no doubt that they will be used in attempts to improve performance. During the
      last years, doping control systems have also been improved: EPO can now be
      detected in urine samples and the detection of AAS has also become much more
      sensitive. However GH hormone detection is not possible at the moment and this
      remains a major weakness of doping control. Other problems are the control
      procedures which are far from being optimal. In the future the quality of doping
      controls will be decisive and not only the quantity; controls will have to be
      "intelligent". The effective fight against doping in the next years will decide
      about the survival of elite sport.

PMID- 18084908
TI  - Creutzfeldt-Jakob disease with slow progression. A mimickry of progressive
      supranuclear palsy.
AB  - Sporadic Creutzfeldt-Jakob disease (sCJD) does not always present with typical
      clinical signs, such as myoclonus in association with periodic sharp-wave
      complexes. We present a 67-year old female patient with initial falls and
      vertical gaze palsy, suggesting the diagnosis of Progressive Supranuclear Palsy
      (PSP). EEG and MRI were not contributory. Typical clinical and paraclinical CJD
      signs were only seen after 17 months. The diagnosis was confirmed by autopsy. -
      CJD can be a neurodegenerative chameleon. The present case adds to the scare
      literature of slowly evolving CJD mimicking Parkinsonism related to tauopathies.

PMID- 18084909
TI  - [Pleural effusion--which diagnosis is significant?].
AB  - Although many different diseases may cause a pleural effusion the most common
      causes are congestive heart failure, pneumonie, and cancer. The first step in the
      diagnosis of pleural effusion is the distinction between exudates and
      transudates. Because of their high sensitivity Light's criteria, which
      differentiate transudative effusions from exudative effusions by measuring the
      levels of total protein and lactate dehydrogenase in the pleural fluid and serum,
      have become the standard method for making this distinction. Aim of this article
      was to mention the various parameters and their usefulness in closer
      characterication of pleural effusion.

PMID- 18084910
TI  - The Rorschach butterfly effect: it L.L. a mistake.
AB  - Errors in Rorschach coding and interpretation have contributed substantially to
      the ink-blot literature, with reported discrepancies on even the simplest scoring
      tasks. A review of the underlying assumptions uncovered a long-standing location
      aberration, stemming from Beck's adaptation of Klopfer and perpetuated through
      Exner. The resulting coding errors (D3 or Dd28, and "o" or "u") in a highly
      scrutinized and regularly selected domain of card II potentiates a "butterfly
      effect" escalation of interpretative malfeasance. It remains unclear whether
      review of the vast data-base of collected protocol summaries will undo the
      cumulative putative error, or whether the creation of a fresh approach to
      Rorschach may be the best way forward for Rorschach in the 21st century.

PMID- 18084911
TI  - [History of the cesarean section "post-mortem"].
AB  - During the 18e century the catholic church insisted on christening babies
      suffering in the womb of their mother. Midwives and doctors were obliged to
      baptize the children, or inside the uterus, or after cesarian section done after
      death of the mother. We found 28 cesarian sections done in dead women in
      Luxembourg by surgeons or by midwives.

PMID- 18084912
TI  - Mother Nature's gifts to diseases of man: the impact of natural products on anti
      infective, anticholestemics and anticancer drug discovery.
AB  - This chapter is designed to demonstrate that compounds derived from nature are
      still in the forefront of drug discovery in diseases such as microbial and
      parasitic infections, carcinomas of many types and control of cholesterol/lipids
      in man. In each disease area we have provided short discussions of past, present
      and future agents, in general only considering compounds currently in clinical
      Phase II or later, that were/are derived from nature's chemical skeletons.
      Finishing with a discussion of the current and evolving role(s) of microbes
      (bacteria and fungi) in the production of old and new agents ostensibly produced
      by higher organisms.

PMID- 18084913
TI  - Drug discovery and development with plant-derived compounds.
AB  - An overview is given on current efforts in drug development based on plant
      derived natural products. Emphasis is on projects which have advanced to clinical
      development. Therapeutic areas covered include cancer, viral infections including
      HIV, malaria, inflammatory diseases, nociception and vaccine adjuvants, metabolic
      disorders, and neurodegenerative diseases. Aspects which are specific to plant
      based drug discovery and development are also addressed, such as supply issues in
      the commercial development, and the Convention on Biological Diversity.

PMID- 18084914
TI  - Evolutionary mechanisms underlying secondary metabolite diversity.
AB  - The enormous chemical diversity and the broad range of biological activities of
      secondary metabolites raise many questions about their role in nature and the
      specific traits leading to their evolution. The answers to these questions will
      not only be of fundamental interest but may also provide lessons that could help
      to improve the screening protocols of pharmaceutical companies and strategies for
      rational secondary metabolite engineering. In this review, we try to dissect
      evolutionary principles leading to the emergence, distribution, diversification
      and selection of genes involved in secondary metabolite biosyntheses. We give an
      overview about recent insights into the evolution of the different types of
      polyketide synthases (PKS) in microorganisms and plants and highlight unique
      mechanisms underlying polyketide diversity. Although phylogenetic and
      experimental data have significantly increased our knowledge about the role and
      evolution of secondary metabolites in the last decades there is still much
      dissent about the impact of natural selection. In order to understand the
      evolution towards metabolic diversity we therefore need more thorough
      investigations of the ecological role of secondary metabolites in the future.

PMID- 18084915
TI  - Biodiversity, chemical diversity and drug discovery.
AB  - Drugs developed from microbial natural products are in the fundaments of modern
      pharmaceutical companies. Despite decades of research, all evidences suggest that
      there must remain many interesting natural molecules with potential therapeutic
      application yet to be discovered. Any efforts to successfully exploit the
      chemical diversity of microbial secondary metabolites need to rely heavily on a
      good understanding of microbial diversity, being the working hypothesis that
      maximizing biological diversity is the key strategy to maximizing chemical
      diversity. This chapter presents an overview of diverse topics related with this
      basic principle, always in relation with the discovery of novel secondary
      metabolites. The types of microorganisms more frequently used for natural
      products discovery are briefly reviewed, as well as the differences between
      terrestrial and marine habitats as sources of bioactive secondary metabolite
      producers. The concepts about microbial diversity as applied to prokaryotes have
      evolved in the last years, but recent data suggest the existence of true
      biogeographic patterns of bacterial diversity, which are also discussed. Special
      attention is dedicated to the existing strategies to exploit the microbial
      diversity that is not easy to tackle by conventional approaches. This refers
      explicitly to the current attempts to isolate and cultivate the previously
      uncultured bacteria, including the application of high throughput techniques.
      Likewise, the advances of microbial molecular biology has allowed the development
      of metagenomic approaches, i.e., the expression of biosynthetic pathways directly
      obtained from environmental DNA and cloned in a suitable host, as another way of
      accessing microbial genetic resources. Also, approaches relying on the genomics
      of metabolite producers are reviewed.

PMID- 18084916
TI  - High impact technologies for natural products screening.
AB  - Natural products have historically been a rich source of lead molecules in drug
      discovery. However, natural products have been de-emphasized as high throughput
      screening resources in the recent past, in part because of difficulties in
      obtaining high quality natural products screening libraries, or in applying
      modern screening assays to these libraries. In addition, natural products
      programs based on screening of extract libraries, bioassay-guided isolation,
      structure elucidation and subsequent production scale-up are challenged to meet
      the rapid cycle times that are characteristic of the modern HTS approach.
      Fortunately, new technologies in mass spectrometry, NMR and other spectroscopic
      techniques can greatly facilitate the first components of the process - namely
      the efficient creation of high-quality natural products libraries, bimolecular
      target or cell-based screening, and early hit characterization. The success of
      any high throughput screening campaign is dependent on the quality of the
      chemical library. The construction and maintenance of a high quality natural
      products library, whether based on microbial, plant, marine or other sources is a
      costly endeavor. The library itself may be composed of samples that are
      themselves mixtures - such as crude extracts, semi-pure mixtures or single
      purified natural products. Each of these library designs carries with it
      distinctive advantages and disadvantages. Crude extract libraries have lower
      resource requirements for sample preparation, but high requirements for
      identification of the bioactive constituents. Pre-fractionated libraries can be
      an effective strategy to alleviate interferences encountered with crude
      libraries, and may shorten the time needed to identify the active principle.
      Purified natural product libraries require substantial resources for preparation,
      but offer the advantage that the hit detection process is reduced to that of
      synthetic single component libraries. Whether the natural products library
      consists of crude or partially fractionated mixtures, the library contents should
      be profiled to identify the known components present - a process known as
      dereplication. The use of mass spectrometry and HPLC-mass spectrometry together
      with spectral databases is a powerful tool in the chemometric profiling of bio
      sources for natural product production. High throughput, high sensitivity flow
      NMR is an emerging tool in this area as well. Whether by cell based or
      biomolecular target based assays, screening of natural product extract libraries
      continues to furnish novel lead molecules for further drug development, despite
      challenges in the analysis and prioritization of natural products hits.
      Spectroscopic techniques are now being used to directly screen natural product
      and synthetic libraries. Mass spectrometry in the form of methods such as ESI
      ICRFTMS, and FACS-MS as well as NMR methods such as SAR by NMR and STD-NMR have
      been utilized to effectively screen molecular libraries. Overall, emerging
      advances in mass spectrometry, NMR and other technologies are making it possible
      to overcome the challenges encountered in screening natural products libraries in
      today's drug discovery environment. As we apply these technologies and develop
      them even further, we can look forward to increased impact of natural products in
      the HTS based drug discovery.

PMID- 18084917
TI  - Virtual screening for the discovery of bioactive natural products.
AB  - In this survey the impact of the virtual screening concept is discussed in the
      field of drug discovery from nature. Confronted by a steadily increasing number
      of secondary metabolites and a growing number of molecular targets relevant in
      the therapy of human disorders, the huge amount of information needs to be
      handled. Virtual screening filtering experiments already showed great promise for
      dealing with large libraries of potential bioactive molecules. It can be utilized
      for browsing databases for molecules fitting either an established pharmacophore
      model or a three dimensional (3D) structure of a macromolecular target. However,
      for the discovery of natural lead candidates the application of this in silico
      tool has so far almost been neglected. There are several reasons for that. One
      concerns the scarce availability of natural product (NP) 3D databases in contrast
      to synthetic libraries; another reason is the problematic compatibility of NPs
      with modern robotized high throughput screening (HTS) technologies. Further
      arguments deal with the incalculable availability of pure natural compounds and
      their often too complex chemistry. Thus research in this field is time-consuming,
      highly complex, expensive and ineffective. Nevertheless, naturally derived
      compounds are among the most favorable source of drug candidates. A more rational
      and economic search for new lead structures from nature must therefore be a
      priority in order to overcome these problems. Here we demonstrate some basic
      principles, requirements and limitations of virtual screening strategies and
      support their applicability in NP research with already performed studies. A
      sensible exploitation of the molecular diversity of secondary metabolites however
      asks for virtual screening concepts that are interfaced with well-established
      strategies from classical pharmacognosy that are used in an effort to maximize
      their efficacy in drug discovery. Such integrated virtual screening workflows are
      outlined here and shall help to motivate NP researchers to dare a step towards
      this powerful in silico tool.

PMID- 18084918
TI  - Strain improvement for production of pharmaceuticals and other microbial
      metabolites by fermentation.
AB  - Microbes have been good to us. They have given us thousands of valuable products
      with novel structures and activities. In nature, they only produce tiny amounts
      of these secondary metabolic products as a matter of survival. Thus, these
      metabolites are not overproduced in nature, but they must be overproduced in the
      pharmaceutical industry. Genetic manipulations are used in industry to obtain
      strains that produce hundreds or thousands of times more than that produced by
      the originally isolated strain. These strain improvement programs traditionally
      employ mutagenesis followed by screening or selection; this is known as 'brute
      force' technology. Today, they are supplemented by modern strategic technologies
      developed via advances in molecular biology, recombinant DNA technology, and
      genetics. The progress in strain improvement has increased fermentation
      productivity and decreased costs tremendously. These genetic programs also serve
      other goals such as the elimination of undesirable products or analogs, discovery
      of new antibiotics, and deciphering of biosynthetic pathways.

PMID- 18084919
TI  - Nutritional and engineering aspects of microbial process development.
AB  - Today we use many drugs produced by microorganisms. However, when these drugs
      were discovered it was found that the yields were low and a substantial effort
      had to be put in to develop commercially viable processes. A key part of this
      endeavor was the studies of the nutritional and the engineering parameters. In
      this chapter, the basic principles of optimizing the nutritional and engineering
      aspect of the production process are described with appropriate examples. It was
      found that two critical components of nutritional medium, carbon and nitrogen
      source regulated the synthesis of the compounds of interest. Rapidly utilizable
      carbon source such as glucose supported the growth but led to catabolite
      repression and alternative carbon sources or methods of addition had to be
      devised. Inorganic nitrogen sources led to undesirable changes in pH of the
      medium. Organic nitrogen sources could influence the yields positively or
      negatively and had to be chosen carefully. Essential nutrients like phosphates
      often inhibited the synthesis and its concentration had to be maintained below
      the inhibitory levels. On many occasions, trace nutrients like metal ions and
      vitamins were found to be critical for good production. Temperature and pH were
      important environmental variables and their optimum values had to be determined.
      The media were designed and optimized initially with 'one variable at a time'
      approach and later with experimental design based on statistics. The latter
      approach is preferred because it is economical, considers interactions between
      medium components and allows rapid optimization of the process. The engineering
      aspects like aeration, agitation, medium sterilization, heat transfer, process
      monitoring and control, become critical as the process is scaled-up to the
      production size. Aeration and agitation are probably the most important
      variables. In many processes dissolved oxygen concentration had to be maintained
      above a critical value to obtain the best yields. The rheological properties of
      fermentation broth significantly affect the aeration and mixing efficiency. The
      removal of heat from the large fermentors can be difficult under certain
      conditions. However, new designs of impellers, availability of sensors to monitor
      important physiological and process variables and advent of computers have
      facilitated successful scale-up of fermentation processes.

PMID- 18084921
TI  - The work of the OIE Biological Standards Commission.
AB  - Founded in 1949 and now composed of five specialist members, this Commission
      establishes or approves methods for diagnosing diseases of mammals, birds and
      bees and for testing biological products, such as vaccines, used for control
      purposes. It oversees the production of the Manual of Diagnostic Tests and
      Vaccines for Terrestrial Animals (the "Terrestrial Manual"), recognised as an
      international standard text under the SPS Agreement of the World Trade
      Organisation. The Commission also selects OIE Reference Laboratories for diseases
      of terrestrial animals, and promotes the preparation and distribution of standard
      reagents for diagnostic testing. Great reliance is placed on the OIE network of
      expertise, and specialists are brought together in Ad hoc groups to address
      specific issues in relation to standardisation of diagnostic tests and vaccines.
      The Commission is elected by the International Committee for a three year term.
      Commission Members should be recognised specialists, with international
      experience, trained in infectious disease diagnosis and/or prevention,
      particularly in the area of laboratory methods.

PMID- 18084920
TI  - Natural products from plant cell cultures.
AB  - Plants produce complex small molecules - natural products - that exhibit
      anticancer, antimalarial and antimicrobial activity. These molecules play a key
      role in human medicine. However, plants typically produce these compounds in low
      quantities, and harvesting plant natural products is frequently expensive, time
      consuming and environmentally damaging. Plant cell culture provides a renewable,
      easily scalable source of plant material. In this chapter we discuss the
      successes and pitfalls associated with natural product production in plant cell
      cultures.

PMID- 18084922
TI  - The work of the OIE Aquatic Animal Health Standards Commission.
AB  - Founded in 1960 as the Fish Diseases Commission, the Aquatic Animal Health
      Standards Commission is currently composed of five members elected by the OIE
      International Committee on a three-year basis. Its remit covers diseases of fish,
      molluscs and crustaceans. OIE stipulates that Commission members should be
      internationally recognised specialists in the fields of methods for surveillance,
      diagnosis and prevention of infectious aquatic animal diseases and have extensive
      international experience, at the regional or global level. The Commission is
      responsible for developing the international standards of the Aquatic Code and
      the Aquatic Manual, very ably supported by various OIE Ad hoc Groups and the
      designated experts at the OIE Reference Laboratories for aquatic animal diseases.
      The latest editions of the Aquatic Code and the Aquatic Manual published in 2006
      incorporate several important modifications including several changes to the list
      of diseases. Work has commenced in new areas such as aquatic animal welfare and
      an assessment of whether amphibian diseases should be included in the work of the
      Commission. Continuing efforts are being made to encourage enhanced involvement
      of veterinary authorities in aquatic animal health and to improve cooperation
      between veterinary and other authorities with competence for aquatic animal
      health.

PMID- 18084923
TI  - The International Atomic Energy Agency (IAEA) experience in the development of
      validation systems leading to the OIE certification of diagnostic assays.
AB  - For the past 15 years, the International Atomic Energy Agency (IAEA) has had a
      major interest in helping its member states to diagnose livestock diseases
      through the development and validation of diagnostic tests for trans-boundary
      animal diseases. In November, 2007, an IAEA consultants meeting attended by
      experts, OIE members and producers reviewed the OIE process for the recognition
      of tests to date. Conclusions concerning the application procedure were tabled by
      the general meeting and then specific producer recommendations were made. Both
      are shown below, along with conclusions regarding referencing in general. Some of
      the points brought up suggest major changes in the idea of trade prescription and
      test status.

PMID- 18084924
TI  - Development of a framework for international certification by the OIE of
      diagnostic tests validated as fit for purpose.
AB  - Historically, the OIE has focussed on test methods applicable to trade and the
      international movement of animals and animal products. With its expanding role as
      the World Organisation for Animal Health, the OIE has recognised the need to
      evaluate test methods relative to specific diagnostic applications other than
      trade. In collaboration with its international partners, the OIE solicited input
      from experts through consultants meetings on the development of guidelines for
      validation and certification of diagnostic assays for infectious animal diseases.
      Recommendations from the first meeting were formally adopted and have
      subsequently been acted upon by the OIE. A validation template has been developed
      that specifically requires a test to be fit or suited for its intended purpose
      (e.g. as a screening or a confirmatory test). This is a key criterion for
      validation. The template incorporates four distinct stages of validation, each of
      which has bearing on the evaluation of fitness for purpose. The OIE has just
      recently created a registry for diagnostic tests that fulfil these validation
      requirements. Assay developers are invited to submit validation dossiers to the
      OIE for evaluation by a panel of experts. Recognising that validation is an
      incremental process, tests methods achieving at least the first stages of
      validation may be provisionally accepted. To provide additional confidence in
      assay performance, the OIE, through its network of Reference Laboratories, has
      embarked on the development of evaluation panels. These panels would contain
      specially selected test samples that would assist in verifying fitness for
      purpose.

PMID- 18084925
TI  - International harmonisation.
AB  - Like several other sectors, animal and public health face new challenges arising
      from the worldwide globalisation phenomenon. To this end, the 4th strategic plan
      specifically addresses reinforcing the capacity of Regional Representations and
      the network of OIE Collaborating Centres and Reference Laboratories and
      implementing networking approaches. A good example of achievements in this field,
      and of overcoming constraints and limits, can be found in veterinary medicinal
      products (VMPs).

PMID- 18084926
TI  - The OIE and the World Association of Veterinary Laboratory Diagnosticians: a new
      partnership.
AB  - The OIE and the WAVLD have many shared goals and aspirations and the Board of
      Directors of the WAVLD are very excited and proud of this new partnership.
      Although the WAVLD is a relatively small organization with limited financial
      means, it is hoped that our relationship with the OIE will allow us to grow and
      to possibly provide services beyond the biennial ISWAVLD educational symposia and
      informal consultations. To be sure, many countries are struggling to build a
      strong veterinary diagnostic laboratory infrastructure to serve their animal
      agricultural industries. War-torn countries like Iraq and Afghanistan are also in
      great need of help in this realm. Few initiatives have the potential to have such
      a huge and positive impact on the people and animals of a country like the
      implementation and operation of a sound veterinary diagnostic laboratory system.
      However, it will take considerable funds to provide the expert assistance that is
      necessary to help build such a system. The WFAH proposal is still under
      consideration by the WAVLD Board. Please contact us with your ideas on this and I
      will share them with the Board. The WAVLD web site is located at: www.wavld.org.

PMID- 18084927
TI  - The changing world of biocontainment and biosecurity.
AB  - Since the 1980s, a number of key events have significantly altered our ideas on
      biosecurity and the role of biocontainment laboratories, such as the bovine
      spongiform encephalopathy (BSE) and severe acute respiratory syndrome (SARS)
      outbreaks and the anthrax episode of 2001 in the USA. This has resulted in the
      development of plans to build "high containment" facilities around the world and
      an array of new regulations at both national and international levels regarding
      the management of pathogens, the operation of high containment facilities, the
      use of genetically modified material, and the transportation of such agents and
      personnel security issues. Considering the cost, however, it is debatable whether
      every country needs to build its own high containment facility. The Australian
      Animal Health Laboratory (AAHL) provides an example of what might be considered
      best practice in biocontainment while considering regulations, cost and need.

PMID- 18084928
TI  - Quality systems in veterinary diagnostics laboratories.
AB  - Quality assurance of services provided by veterinary diagnostics laboratories is
      a fundamental element promoted by international animal health organizations to
      establish trust, confidence and transparency needed for the trade of animals and
      their products at domestic and international levels. It requires, among other
      things, trained personnel, consistent and rigorous methodology, choice of
      suitable methods as well as appropriate calibration and traceability procedures.
      An important part of laboratory quality management is addressed by ISO/IEC 17025,
      which aims to facilitate cooperation among laboratories and their associated
      parties by assuring the generation of credible and consistent information derived
      from analytical results. Currently, according to OIE recommendation, veterinary
      diagnostics laboratories are only subject to voluntary compliance with standard
      ISO/IEC 17025; however, it is proposed here that OIE reference laboratories and
      collaboration centres strongly consider its adoption.

PMID- 18084929
TI  - Regulatory constraints for the transport of samples and compliance with the World
      Organisation for Animal Health (OIE) standards for biosecurity and
      biocontainment.
AB  - The International Regulations for transport of infectious substances, including
      diagnostic specimens, are based on the United Nations Model Regulations and are
      the standard for transport by all means of transportation including air
      transport; the International Air Transport Association (IATA) regulation
      specifically addresses air shipment. In 2005 and 2006 there were major
      improvements in the procedures for shipping infectious substances. These
      substances are divided into Category A, which includes primarily cultures of the
      more pathogenic agents and Category B, all the other substances. Category A
      shipments must have a Dangerous Goods Certificate and meet other requirements.
      Category B shipments, which include most diagnostic tissue specimens, do not.
      These regulations specifically exempt certain substances, including those that
      have been neutralized or inactivated to destroy pathogens and samples from
      "normal" animals. The packaging requirements help insure that biocontainment is
      maintained during shipment to protect the shipper and the environment. The
      packaging requirements and the shipping procedures provide a chain of custody and
      assist in supporting biosecurity. The more stringent Category A requirements
      provide increased biocontainment and biosecurity safeguards for these potentially
      more dangerous substances. In addition, National requirements, such as import
      permits and the US select agent requirements, provide an added measure of
      biocontainment and biosecurity.

PMID- 18084930
TI  - WAHIS and the role of the OIE's reference laboratories and collaborating centres.
AB  - In May 2004, OIE Member Countries adopted a resolution on the implementation of a
      new notification procedure. This new notification procedure led to the creation
      of a new World Animal Health Information System, which came into force in January
      2005. In April 2006, the OIE launched a secure web application called the World
      Animal Health Information System (WAHIS), an online notification system for
      Member Countries. For countries with fully functional internet connections, this
      new system has replaced the use of paper report forms. It constitutes a major
      achievement in the worldwide use of information technology and modem
      communication techniques and their applications, enabling Member Countries to
      notify the OIE of disease and epidemiological information in accordance with the
      requirements laid down in Chapter 1.1.2. of the Terrestrial Animal Health Code
      and Chapter 1.2.1. of the Aquatic Animal Health Code. As well as being an online
      notification system, WAHIS is also a two-way communication system. It goes
      without saying that a good flow of information is essential if the system is to
      function optimally. WAHIS thus serves to disseminate information to OIE Member
      Countries in addition to such information being publicly disseminated via
      distribution lists and the World animal Health Information Database (WAHID)
      interface. It can also be used to ask a country to provide explanations or
      clarifications on the data it has submitted.

PMID- 18084931
TI  - The new policy of the Food and Agriculture Organization of the United Nations and
      its Reference Centres for the Animal Production and Health Division.
AB  - The article explains the current procedures to be followed for institutes that
      are, were or would like to become Reference Centres for the Food and Agriculture
      Organization (FAO) of the United Nations. Within the realm of animal health many
      of the Reference Laboratories and Reference Centres of the World Organisation for
      Animal Health (OIE) are the same as those of the Animal and Health Division of
      FAO, particularly for diseases that are transboundary in nature, but they also
      address other aspects concerning health, production, standard setting,
      agriculture, conservation, water, and biotechnology.

PMID- 18084932
TI  - Responses to a questionnaire on networking between OIE Reference Laboratories and
      OIE Collaborating Centres.
AB  - Two separate questionnaires were distributed to 20 OIE Collaborating Centres and
      160 OIE Reference Laboratories to assess the current status of networking and
      collaboration among OIE Reference Laboratories and between OIE Reference
      Laboratories and OIE Collaborating Centres. The questionnaire for the OIE
      Reference Laboratories contained 7 sections with questions on networking between
      laboratories, reporting of information, biosecurity quality control, and
      financing. Emphasis was placed in obtaining information on inter-laboratory
      relationships and exchange of expertise, training needs and sharing of data and
      information. The questionnaire for the OIE Collaborating Centres contained six
      sections with the emphasis on aspects related to awareness of services that can
      be provided, expertise that could be made available, sharing of information and
      the relationship with the national veterinary services of the countries
      concerned. The responses to the questionnaires were collated, categorised and
      statistically evaluated to allow for tentative inferences on the data provided.
      Valuable information emanated from the data identifying the current status of
      networking and indicating possible shortcomings that could be addressed to
      improve networking.

PMID- 18084933
TI  - Developing standards: the role of the OIE expert.
AB  - The increasingly global nature of animal trade, along with greater focus on
      improving the production and trading opportunities for emerging nations has
      highlighted the need for a more standardised, harmonised approach to
      standardisation of diagnostics and prophylaxis. This has driven a need, on the
      part of both the competent authorities of member countries and international
      agencies, for OIE itself to develop its role as the repository and source of
      expertise in these fields. With this role has emerged a strong demand to develop
      standardisation and harmonisation of diagnostic processes, along with an ever
      expanding role played by the OIE Reference Expert in networking and consultancy.
      This expansion comes at a price, both in terms of the burden on Reference
      Laboratories and the financial cost of the activities themselves. Accordingly,
      the role of the Reference Expert is pivotal, both in improving standards and in
      assuring the viability of the Reference Laboratory they represent. At a higher
      level, the need for strategic changes are highlighted, involving establishment of
      networks to share the burden and increase efficiency of delivery, along with
      greater interaction among international agencies and assistance in providing
      project-based financial support. Closer collaboration with the diagnostics and
      vaccine industries is also foreseen, which, if managed properly, will provide
      benefits to OIE Reference Laboratories through income to support their
      activities, to national laboratories thorough advanced, reliable and validated
      tests and, ultimately, to animal health itself, at the global level.

PMID- 18084934
TI  - International reference laboratory networks: challenges and benefits.
AB  - A number of different models can be used to demonstrate how laboratories working
      together across international boundaries can generate information that cannot be
      achieved by any one institution working in isolation. Networks can facilitate
      exchanges of data, of people and of biological materials. Constraints to this
      process include funding, protection of intellectual property rights,
      communication barriers, and regulatory controls (e.g. on shipment). Examples
      include informal networks set up at laboratories' own initiative, formal
      "Networks of Excellence" established and funded by the European Union, and global
      initiatives inspired by international organisations such as the OIE, FAO and WHO.

PMID- 18084935
TI  - Experiences of an OIE Collaborating Centre in molecular diagnosis of
      transboundary animal diseases: a review.
AB  - The highly contagious transboundary animal diseases (TADs), e.g., foot-and-mouth
      disease (FMD), classical swine fever (CSF), African swine fever (ASF) and highly
      pathogenic avian influenza (HPAI) are regularly occurring and re-occurring on
      various continents, causing severe losses. This epidemiological situation
      indicates the urgent need for the development of powerful, robust and high
      capacity new diagnostic methods in order to detect and identify the causative
      agents very rapidly. This report is on the experiences of an OIE Collaborating
      Centre and those of the MULTIPLEX-PCR and the LAB-ON-SITE EU project consortia
      with the deveopment of novel methods for the improved molecular diagnosis of a
      range of viral diseases. Thermal amplification based real-time PCR methods
      (e.g.,TaqMan, Molecular Beacons, Primer-Probe Energy Transfer, and Light Upon
      eXtension (LUX) fluorogenic primers), and amplification without thermocycling
      have been elaborated for the improved diagnosis of TADs, such as FMD, swine
      vesicular disease, vesicular stomatitis, CSF, ASF, HPAI and Newcastle disease
      (ND). The simultaneous detection of various pathogens in a disease complex is
      facilitated by the development of multiplex PCR packages. By introducing nucleic
      acid extraction and pipetting robotics, together with the multi-channel real-time
      PCR machines, the molecular diagnostic procedures have become rapid, robust and
      automated. Quality control is strengthened by special precautions to avoid false
      positive and false negative results. By following the steps of OIE
      standardisation and validation, the diagnostic PCR assays have become nationally
      and nternationally standardised and harmonised. The development of additional
      methods, like padlock probes and microarrays, is further improving the arsenal of
      nucleic acid based novel molec ular diagnostic tests for TADs.

PMID- 18084936
TI  - The OIE concept of laboratory twinning.
AB  - Laboratory twinning was introduced in 2002, but it was never really taken on
      board by either OIE Reference Laboratories or OIE Member Countries in need of
      twinning arrangements. Recent developments in global animal health and an
      increase in the potential for the rapid global spread of animal diseases and
      pathogens call for the development and implementation of this concept. The most
      effective way of detecting, diagnosing, controlling and responding to animal
      disease and zoonotic incursions is to assure good governance in Member Countries.
      For this ideal to be realised, the concept laboratory twinning was born to
      support the development of an even geographical distribution of expertise and
      Reference Laboratories to facilitate access to experts and the rapid detection
      and diagnosis of disease. Developing and intransition countries are also in
      urgent need of better access to scientific expertise to be able to justify and
      formulate animal health control strategies and assist in the OIE standard setting
      process.

PMID- 18084937
TI  - How to improve the efficiency of veterinary laboratories.
AB  - Veterinary laboratories around the globe are currently facing a number of
      important challenges. These challenges include an ageing workforce, lack of
      trained veterinary specialists, increased stringency for test validation,
      increasing emphasis on quality management, safety standards and certified
      accreditation processes, increasing regulation and audit processes and high costs
      of replacement infrastructure. Importantly, increased collaboration and linkages
      are high on the agenda in most countries to enhance efficiency within the sector.
      In Australia, mechanisms are in place to deal with some of these issues, and it
      is likely similar mechanisms are being used in other countries. The issues and
      some possible solutions are discussed.

PMID- 18084938
TI  - Reference laboratory networking: the European experience in brucellosis.
AB  - Over the past forty years, a huge effort of standardisation of tests and
      harmonisation of sanitary policies and requirements has been made in the European
      Union (EU). The EU has itself greatly evolved in its size and policies. Voluntary
      uncoordinated actions initially had some success but not enough to attain a level
      of standardisation compatible with a single market and to achieve the sanitary
      level foreseen by the community. The creation of a Community Reference laboratory
      with specific responsibilities and tasks and the provision of adequate financial
      assistance is expected to lead to better co-ordination of activities and to
      ensure international harmonisation of tests and procedures.

PMID- 18084939
TI  - The role of diagnostic laboratories in support of animal disease surveillance
      systems.
AB  - Diagnostic laboratories are an essential component of animal disease surveillance
      systems. To understand the occurrence of disease in populations, surveillance
      systems rely on random or targeted surveys using three approaches: clinical,
      serological and virological surveillance. Clinical surveillance is the basis for
      early detection of disease and is usually centered on the detection of syndromes
      and clinical findings requiring confirmation by diagnostic laboratories. Although
      most of the tests applied usually perform to an acceptable standard, several have
      not been properly validated in terms of their diagnostic sensitivity and
      specificity. Sensitivity and specificity estimates can vary according to local
      conditions and, ideally, should be determined by national laboratories where the
      tests are to be applied. The importance of sensitivity and specificity estimates
      in the design and interpretation of statistically based surveys and risk analysis
      is fundamental to establish appropriate disease control and prevention
      strategies. The World Organisation for Animal Health's (OIE) network of reference
      laboratories acts as centers of expertise for the diagnosis of OIE listed
      diseases and have a role in promoting the validation of OIE prescribed tests for
      international trade. This paper discusses the importance of the epidemiological
      evaluation of diagnostic tests and the role of the OIE Reference Laboratories and
      Collaborating Centres in this process.

PMID- 18084940
TI  - Resolution: strengthening the networking between OIE Reference Laboratories, OIE
      Collaborating Centres and National Veterinary Laboratories to enhance the even
      global spread of veterinary scientific knowledge and expertise.

PMID- 18084941
TI  - Pancreatic cancer: step by step forward.

PMID- 18084942
TI  - CT and MR imaging of pancreatic cancer.
AB  - Computed tomography (CT) and magnetic resonance imaging (MRI) are emerging
      noninvasive techniques for imaging of the pancreas. Based on multislice
      technology, CT enables multiplanar imaging of the pancreas (multislice-CT, MSCT)
      with a high contrast between vessels and parenchyma. In addition, MRI of the
      pancreas including the imaging of the lumina of the biliary tree and the
      pancreatic duct (magnetic resonance cholangiopancreaticography, MRCP) and the
      abdominal vessels (MR angiography, MRA) has become available for daily clinical
      practice in most hospitals. The addition of multiplanar and curved reformations
      may increase the sensitivity of CT and improves its agreement with surgical
      findings. Beyond abdominal MR imaging, techniques such as magnetic resonance
      cholangiopancreaticography (MRCP) and MR angiography should be integrated in the
      imaging protocol whenever possible.

PMID- 18084943
TI  - Nuclear medical methods for the diagnosis of pancreatic cancer: positron emission
      tomography.
AB  - The functional imaging approach of nuclear medicine offers important information
      for the characterization of a tumor's pathobiology. In oncology, positron
      emission tomography (PET) especially has had great impact on the staging of tumor
      patients and the assessment of therapy. Both the development of new, tumor
      specific, tracers and the introduction of by software- and hardware-driven image
      fusion emphasize the potential of this modality for an all-embracing diagnostic
      modality.

PMID- 18084944
TI  - Surgical techniques for resectable pancreatic cancer.
AB  - Pancreatic cancer is a highly aggressive cancer with a rising incidence in most
      European countries. Due to both the aggressive biology of the disease and the
      late diagnosis in many cases, pancreatic duct carcinoma is still a disease with a
      poor prognosis. Today, surgical resection of localized tumor remains the only
      potentially curative option available for these patients. Advances in surgical
      techniques and perioperative care has improved significantly in the last 20
      years, causing an extension of indications for surgical intervention. However,
      despite new diagnostic techniques, the surgical exploration still plays the key
      role for the finally assessment of resectability. For evaluation of local
      resectability, laparoscopy alone cannot generally be recommended today and
      explorative laparotomy is required. Contraindications for pancreatic resection
      are liver metastasis, peritoneal metastasis, and tumor infiltration of visceral
      arteries. The surgical management of pancreatic cancer consists of two phases:
      first, assessment of tumor resectability and second, if resectability is given,
      the pancreaticoduodenectomy with consecutive reconstruction. Standard surgical
      strategies are the classic pancreaticoduodenectomy including a distal gastrectomy
      and the pylorus-preserving pancreaticoduodenectomy (PPPD) preserving antral and
      pyloric function, respectively. Both surgical procedures are equally effective
      for the treatment of pancreatic carcinoma. Delicate lymphadenectomy during
      pancreaticoduodenectomy is important for radical oncological enforcement. An
      extended lymphadenectomy showed no benefit in several trials. Despite the
      encouraging advances in surgical treatment, actuarial 5-year survival rates after
      pancreatic resection are only at about 20%.

PMID- 18084945
TI  - Postoperative staging of pancreatic cancer.
AB  - Pancreatic cancer is a devastating disease with a 5-year survival rate of 3%-5%.
      The mortality of pancreatic cancer is almost identical with its incidence. The
      vast majority are pancreatic ductal adenocarcinomas. It is typically a tumour of
      the elderly. The main risk factor is smoking. Clinical and histopathological
      studies have identified pancreatic cancer precursor lesions. These include
      pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous
      neoplasia (IPMN) and mucinous cystic neoplasm (MCN). To improve patient
      prognosis, surgical interventions have become more aggressive, including
      pancreaticoduodenectomy and more or less radical lymphadenectomy. Following
      surgery, it is the surgical pathologist who provides valuable information
      regarding the exact tumour localization, histological tumour type, grading,
      completeness of resection, nodal status and the presence of precursor lesions.
      Although many tissue-based prognostic biomarkers have been characterized and can
      be studied by immunohistochemistry or molecular biological techniques, their
      impact on patient management and treatment is still limited. More recently
      proteomic profiling has raised hopes for early cancer detection, thereby
      improving the prognosis of pancreatic cancer patients.

PMID- 18084946
TI  - Adjuvant therapy in patients with pancreatic cancer.
AB  - The prognosis for patients with pancreatic cancer is still very poor. A complete
      (R0) surgical resection of the tumor poses the only chance of cure. At the moment
      only postoperative chemotherapy with gemcitabine has significantly delayed the
      development of recurrent disease and showed an improvement in long-term survival
      compared to observation alone. It is essential to develop more effective adjuvant
      therapy strategies with involvement of all therapeutic options to change the
      disappointing situation.

PMID- 18084947
TI  - First-line chemotherapy in advanced pancreatic cancer.
AB  - This chapter focuses on first-line therapy in inoperable pancreatic cancer.

PMID- 18084948
TI  - Second-line chemotherapy in advanced pancreatic cancer.
AB  - This chapter focuses on second-line therapy in inoperable pancreatic cancer.

PMID- 18084949
TI  - Neoadjuvant and adjuvant strategies for chemoradiation.
AB  - There is an increasing body of evidence showing that patients with resectable
      pancreatic cancer might benefit from adjuvant therapy. Based on phase III trials,
      potential options for adjuvant treatment are chemotherapy alone or a multimodal
      approach involving radiotherapy. Available data are heterogeneous and have been
      discussed controversially. Hitherto, a worldwide standard of care has not yet
      been established. Adequate patient selection might be the key element for a
      tailored adjuvant treatment. Clinical research currently focusses on gemcitabine
      alone or in combination, and some molecular biologic approaches with epidermal
      growth factor receptor monoclonal antibodies (EGFR-MoABs) and anti-angiogenic
      drugs. Recent advances in radiooncology offer better dose conformality and
      reduced morbidities. Currently, the co-operative Radiotherapy and
      Gastrointestinal Groups have launched a multicentric European Organization for
      Research and Treatment of Cancer (EORTC) trial investigating the impact of
      radiotherapy in combination with gemcitabine in R0-resected pancreatic head
      cancer.

PMID- 18084950
TI  - Primary advanced unresectable pancreatic cancer.
AB  - Median as well as overall survival of pancreatic cancer patients in the advanced
      stage is extremely low despite advances in cancer therapy regarding tumor cell
      biology, therapy resistance, and diagnosis. In matters of chemoradiation therapy
      (CRT) in locally advanced pancreatic cancer, favorable positive effect has been
      reached with different radiotherapy proceedings such as intraoperative radiation
      therapy with or without external chemo-/radiation therapy or with CRT alone with
      regard to local tumor pain, local tumor remission, or local control of disease
      and overall survival. Primary (chemo-) radiation therapy only rarely leads to
      local remission. Intraoperative radiation therapy (IORT) merely reaches pain
      palliation in most cases. By administering up-to-date primary CRT, especially
      with gemcitabine-associated CRT, local remission in up to 50% of patients can be
      observed. By applying neoadjuvant CRT, better resectability and the reduction of
      postoperative positive lymph node metastasis has been seen in patients with
      resectable or possibly resectable pancreatic cancer. With primary CRT,
      resectability can also be achieved in patients with primary unresectable
      pancreatic cancer. It has been shown at the evaluation of patients' progression
      samples--either treated with neoadjuvant or primarily with radiotherapy (with
      conventional radiation technique)--that the rate of local recurrence or local
      progression can be reduced in comparison with historical cohorts. By contrast,
      the rate on distant metastases was not affected. Whereas concurrent CRT leads to
      favorable local tumor control, this procedure has a minor effect as to the
      survival in most of the studies. Because metastases occur mostly out of the
      irradiation field and because of partly advanced local tumor progression, the
      concept of combined CRT with continuing chemotherapy was developed. Median
      survival of pancreatic patients in the advanced stage is approx. 3-5 months, with
      a 12-month survival probability of 10% despite advances in cancer therapy. On the
      other hand, the 5-year survival probability is 0.4%-3.0%. The causes of such a
      dismal prognosis can be understood first of all in the commonly late diagnosis,
      second in the aggressive tumor cell biology with continuing therapy resistance,
      and finally because an acceptable resection rate can be achieved only in
      specialized centers. Only 10%-15% of patients can be resected after the diagnosis
      of pancreatic cancer. Resection is considered a potential curative therapy.
      However, median survival of these patients amounts to only 13-18 months, with a 5
      year survival of 10%-20%. The survival rate did not improve with a radical
      resection and extended lymphadenectomy. Furthermore, 15%-30% of primary
      nonmetastatic pancreatic cancer is unresectable due to extended vessel
      infiltration at time of diagnosis. The prognosis for these patients is very
      dismal due to lack of specific therapy; moreover, median overall survival is a
      maximum of 6-8 months.

PMID- 18084951
TI  - Brachytherapy of liver metastases.
AB  - Brachytherapy for the treatment of liver metastases is a novel approach. In this
      procedure, techniques of locally ablative treatment in interventional radiology
      and radiation therapy are combined. After computed tomography (CT)-guided
      percutaneous implantation of catheters into the hepatic tumor, the irradiation is
      performed in an afterloading technique. This minimally invasive procedure offers
      circumscriptive high-dose rate irradiation of the lesion to treat in a single
      session, irrespective of breathing motion or potential cooling effects of
      neighboring vessels. Good local control rates have been achieved in several tumor
      entities, including both secondary and primary malignancies of the liver. This
      article gives an overview of the application technique, possible adverse events,
      and outcome with special attention to the pancreatic cancer scenario.

PMID- 18084952
TI  - Detection of disease recurrence and monitoring of therapy.
AB  - The detection of disease recurrence and treatment monitoring pose high demands on
      diagnostic modalities. Whereas serum marker levels in most cases allow an
      assessment of tumor load and a respective response to therapy, they do not confer
      information on the localization of disease. Although this diagnostic gap is
      filled by imaging modalities, most techniques based on morphology will come to a
      limit when fibrotic tissue alterations have to be differentiated from viable
      tumor tissue in case of suspected recurrence or when residual masses after
      chemotherapy have to be assessed. The metabolic information on tumor cells gained
      by fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging appears not
      only to be more sensitive and reliable in this respect, but also appears to allow
      assumptions on response to therapy, and ultimately on patient prognosis.

PMID- 18084953
TI  - Surgical palliation of advanced pancreatic cancer.
AB  - In about 80% of patients with pancreatic cancer surgical resection is not
      feasible at the time of diagnosis. Therefore, palliative treatment plays a key
      role in the treatment of pancreatic cancer. The defined goals of palliative
      treatment are: reduction of symptoms, reduction of in-hospital stays, and an
      adequate control of pain. In patients with nonresectable pancreatic carcinoma the
      leading goal of palliative strategies should be the control of biliary and
      duodenal obstructions such as jaundice-associated pruritus or sustained nausea
      and vomiting due to gastric outlet obstruction. Although the role of endoscopy
      for palliation has been increasing, operative palliation is still indicated in
      selected cases. Obstructive jaundice is found in approximately 70% of patients
      suffering from carcinoma of the pancreatic head at diagnosis and has to be
      eliminated to avoid progressive liver dysfunction and liver failure. In up to 50%
      of patients with pancreatic cancer, clinical symptoms such as nausea and vomiting
      occur. For the treatment of malignant biliary obstructions in patients with
      pancreatic carcinoma, endoscopic biliary drainage is the option of first choice.
      In case of persistent stent-problems such as occlusion or recurrent cholangitis,
      a hepaticojejunostomy should be considered. The role of a prophylactic
      gastroenterostomy is still under discussion. In patients with combined biliary
      and gastric obstruction a combined bypass should be performed to avoid a second
      operation. The significance of laparoscopic biliary bypass is not yet clear. A
      surgical, minimally invasive approach for treating bile duct obstruction is not
      the standard nowadays. The role of surgical pain relief is mostly negligible
      today. Computed tomography (CT)- or EUS-guided celiac plexus neurolysis has
      replaced surgical intervention today. The significance of palliative resections
      is currently a controversial topic. However, beyond controlled randomized
      studies, a palliative pancreaticoduodenectomy in patients with advanced
      pancreatic carcinoma cannot be recommended at this time.

PMID- 18084954
TI  - Antiangiogenic strategies in pancreatic cancer.
AB  - Since the introduction of gemcitabine in the treatment of pancreatic cancer,
      progress in the use of combination chemotherapies has been very limited. Of the
      different novel options, antiangiogenic treatment strategies are among those
      being intensively studied in preclinical and clinical settings of adenocarcinoma
      of the pancreas. Phase I and limited-size phase II studies using drugs with
      antiangiogenic properties have reported encouraging results. Overall, the results
      of phase III studies with some metalloprotease inhibitors and bevacizumab have so
      far failed to demonstrate a survival benefit for these drugs. Further
      investigations that will take into account the heterogeneity of pancreatic cancer
      are warranted using these or other antiangiogenic active substances.

PMID- 18084955
TI  - Targeted therapy of the epidermal growth factor receptor in the treatment of
      pancreatic cancer.
AB  - The epidermal growth factor receptor (EGFR)-mediated pathway is one of the most
      promising targets for the development of new strategies in anticancer treatments.
      The so-called "small molecule" tyrosine kinase inhibitor erlotinib has gained
      marketing authorization in the United States for advanced adenocarcinoma of the
      lung and for pancreatic cancer, whereas the antibody cetuximab is registered for
      metastatic colorectal cancer and cancers of the head and neck. Ongoing studies
      are evaluating the impact of EGFR-targeting therapy in the treatment of locally
      advanced and metastatic pancreatic cancer.

PMID- 18084956
TI  - Antisense therapeutics for tumor treatment: the TGF-beta2 inhibitor AP 12009 in
      clinical development against malignant tumors.
AB  - Overexpression of the cytokine transforming growth factor-beta 2 (TGF-beta2) is a
      hallmark of various malignant tumors including pancreatic carcinoma, malignant
      glioma, metastasizing melanoma, and metastatic colorectal carcinoma. This is due
      to the pivotal role of TGF-beta2 as it regulates key mechanisms of tumor
      development, namely immunosuppression, metastasis, angiogenesis, and
      proliferation. The antisense technology is an innovative technique offering a
      targeted approach for the treatment of different highly aggressive tumors and
      other diseases. Antisense oligonucleotides are being developed to inhibit the
      production of disease-causing proteins at the molecular level. The
      immunotherapeutic approach with the phosphorothioate oligodeoxynucleotide AP
      12009 for the treatment of malignant tumors is based on the specific inhibition
      of TGF-beta2. After providing preclinical proof of concept, the safety and
      efficacy of AP 12009 were assessed in clinical phase I/II open-label dose
      escalation studies in recurrent or refractory high-grade glioma patients. Median
      survival time after recurrence exceeded the current literature data for
      chemotherapy. Currently, phase I/II study in advanced pancreatic carcinoma,
      metastatic melanoma, and metastatic colorectal carcinoma and a phase IIb study in
      recurrent or refractory high-grade glioma are ongoing. The preclinical as well as
      the clinical results implicate targeted TGF-beta2 suppression as a promising
      therapeutic approach for malignant tumor therapy.

PMID- 18084957
TI  - NF-kappaB as a molecular target in the therapy of pancreatic carcinoma.
AB  - The constitutive activation of the transcription factor nuclear-factor kappa B
      (NF-kappaB) is a hallmark of many highly malignant tumours such as the pancreatic
      ductal adenocarcinoma and accounts for profound chemoresistance. Inhibition of NF
      kappaB activation has been shown to be a useful strategy for increasing the
      sensitivity towards cytostatic drug treatment in vitro and in vivo. Moreover,
      various pharmacological substances (e.g. thalidomide, bortezomib, sulphasalazine)
      have already entered clinical studies partially showing promising results for
      certain types of cancer. Further studies will be needed, in particular for
      pancreatic ductal adenocarcinoma, to evaluate the therapeutic efficacy of
      appropriate combinations of a NF-kappaB inhibitor and cytostatic drugs.

PMID- 18084958
TI  - Immunotherapeutic approaches in pancreatic cancer.
AB  - With growing understanding of the regulation of immune responses, multiple new
      immunotherapeutic targets have evolved. This article gives a survey over the
      current approaches in pancreatic cancer therapy including peptide vaccinations,
      unspecific immunotherapy, allogene modified tumor cell vaccines, and vector-based
      vaccines. Although several trials have shown detectable immune responses, such as
      delayed-type hypersensitivity reactions and cytokine release in enzyme-linked
      immunosorbent spot (ELISPOTS) assays, and some have reported prolonged survival
      for immune responders, immunotherapy remains experimental. However, some
      approaches have made it into a phase III setting. In addition, the emerging
      concept of tumor stem cells may lead to a new focus on immunotherapy, since these
      often highly chemotherapy-resistant cells are thought to be the source of
      recurrences.

PMID- 18084959
TI  - Src kinase and pancreatic cancer.
AB  - The c-Src non-receptor tyrosine kinase is overexpressed in a large number of
      human malignancies. It is linked to tumour development and progression to distant
      metastases by promoting cell proliferation, invasion, and motility. Recently,
      promising anticancer therapeutics targeting c-Src have been developed that are
      under clinical investigation.

PMID- 18084960
TI  - Silence and dissent.

PMID- 18084962
TI  - Skipping for herceptin funds.

PMID- 18084963
TI  - There's trouble in the chook house.

PMID- 18084964
TI  - Asking about abuse and assessing for family violence--part of nurses' caring
      role.

PMID- 18084965
TI  - Deconstructing the 'obesity epidemic'.

PMID- 18084966
TI  - Developing a therapeutic alliance in an eating disorders unit.

PMID- 18084967
TI  - Interprofessional learning--the solution to collaborative practice in primary
      care.

PMID- 18084968
TI  - Examining the draft competencies for nurse practitioners.

PMID- 18084969
TI  - How to conquer anxiety and even enjoy giving a presentation.

PMID- 18084970
TI  - Exploring the complex nature of rural nursing.

PMID- 18084971
TI  - The importance of managing performance processes well.

PMID- 18084972
TI  - Nurses' obligations in a pandemic or disaster.

PMID- 18084973
TI  - Sevoflurane.

PMID- 18084974
TI  - ARF, ATN or AKI? It's now acute kidney injury.

PMID- 18084975
TI  - Inoprotection: the perioperative role of levosimendan.
AB  - Levosimendan is emerging as a novel cardioprotective inotrope. Levosimendan
      augments myocardial contractility by sensitising contractile myofilaments to
      calcium without increasing myosin adenosine triphosphatase activity or oxygen
      consumption. Levosimendan activates cellular adenosine triphosphate-dependent
      potassium channels, a mechanism which is postulated to protect cells from
      ischaemia in a manner similar to ischaemic preconditioning. Levosimendan may
      therefore protect the ischaemic myocardium during ischaemia-reperfusion as well
      as improve the contractile function of the heart. Adenosine triphosphate
      dependent potassium channel activation by levosimendan may also be protective in
      other tissues, such as coronary vascular endothelium, kidney and brain. Clinical
      trials in patients with decompensated heart failure and myocardial ischaemia show
      levosimendan to improve haemodynamic performance and potentially improve
      survival. This paper reviews the known pharmacology of levosimendan, the clinical
      experience with the drug to date and the potential use of levosimendan as a
      cardioprotective agent during surgery.

PMID- 18084976
TI  - Pulsed radiofrequency: a critical review of its efficacy.
AB  - Pulsed radiofrequency is a growingly popular pain treatment modality. However,
      its clinical efficacy remains controversial. In this review, the available
      literature on pulsed radiofrequency is critically analysed to determine its
      clinical efficacy. Our search of the literature for pulsed radiofrequency yielded
      341 citations; after reviewing the abstracts we found 51 relevant articles. There
      were 4 review articles: 44 articles pertained to the application of pulsed
      radiofrequency by an electrode placed in the vicinity of a neural structure. Of
      these only two were randomised controlled trials. Of the remaining 42 articles,
      one was a non-randomised controlled trial, three were prospective uncontrolled
      trials: there were six retrospective studies, 11 case reports, eight laboratory
      studies, two position papers, five editorials and seven items of correspondence,
      while one publication reported two studies. Three articles pertained to
      transcutaneous application of pulsed radiofrequency. Of the two randomised
      controlled trials, one reported efficacy of the pulsed radiofrequency while the
      other reported it to be ineffective. The majority of the uncontrolled and
      observational studies reported clinical efficacy of pulsed radiofrequency,
      however many of these studies had limitations. Further randomised controlled
      clinical trials are recommended in order for the practising pain physician to
      clearly understand the role of pulsed radiofrequency in the treatment of various
      chronic pain syndromes.

PMID- 18084977
TI  - Thrombocytopenia in septic shock patients--a prospective observational study of
      incidence, risk factors and correlation with clinical outcome.
AB  - The objectives of the study were to study the incidence of various degrees of
      severity of thrombocytopenia in septic shock, the risk factors for its
      development and the correlation with clinical outcome. Complete blood counts,
      chemistry panel, arterial lactate, serum cortisol, APACHE II score, logistic
      organ dysfunction score and SOFA score were determined in 69 septic shock
      patients within 24 hours of admission or onset of septic shock. We followed the
      patients until they died or for six months to determine the mortality rate. The
      incidence of thrombocytopenia in our study group was 55%. Patients with
      thrombocytopenia had significantly higher serum creatinine, SOFA score,
      vasopressor requirement, lower PaO2/FiO2 ratio and higher mortality than those
      without thrombocytopenia (P < 0.05). Higher SOFA score, low P(a)O2/FiO2 ratio and
      high vasopressor dose were independent risk factors for development of
      thrombocytopenia. The presence of thrombocytopenia had significant correlation
      with SOFA score (P = 0.008). On receiver-operator characteristic curve analysis,
      platelet count was found to be predictive of increased mortality (area under
      curve = 0.56). Thrombocytopenic patients had 1.4 times the risk of mortality and
      lower survival probability at six months (log rank test P = 0.03). In conclusion,
      thrombocytopenia is common in septic shock and is associated with worse clinical
      outcome. Higher SOFA score, low P(a)Os/FiO2 ratio and high vasopressor dose are
      independent risk factors for development of thrombocytopenia in septic shock.

PMID- 18084978
TI  - Drug abuse and dependency during pregnancy: anaesthetic issues.
AB  - Drug abuse is a significant social problem that can lead to serious obstetric
      complications, some of which may be confused with pregnancy-related disease
      states. Substance abuse poses a number of challenges with respect to the
      management of pain and the conduct of anaesthesia in the peripartum period. This
      review was based on information from a literature search of epidemiological,
      research and review papers on substance abuse during pregnancy, obtained for the
      purpose of preparing a background paper for the Ministerial Council on Drug
      Strategy, Commonwealth Government of Australia. Given that almost 80% of
      substance-abusing parturients require anaesthetic services in the perinatal
      period, early antenatal referral for anaesthetic review is recommended. To
      optimise the care of these vulnerable patients, obstetricians, general
      practitioners and midwives should attempt to identify substance-abusing
      parturients and refer them to an anaesthetist. A careful anaesthetic evaluation
      with non-judgemental questioning is essential, with management tailored to
      individual patient needs and the urgency of obstetric intervention for vaginal
      delivery or caesarean section. Opioid-dependent women, in particular, benefit
      from antenatal pain management planning. Patients recovering from drug addiction
      should also have a well-documented analgesic strategy. A multidisciplinary
      approach will involve obstetricians, anaesthetists and staff of the Drug and
      Alcohol Service. In acute admissions of women by whom antenatal care was not
      accessed, a high index of suspicion for illicit drug use should arise. Because
      illicit substance use is so prevalent, if untoward reactions occur during an
      otherwise uneventful anaesthetic, the possibility of drug abuse should be
      considered.

PMID- 18084979
TI  - Propofol-induced changes in myoplasmic calcium concentrations in cultured human
      skeletal muscles from RYR1 mutation carriers.
AB  - Malignant hyperthermia is a pharmacogenetic disorder caused by autosomal dominant
      mutations in the ryanodine receptor type 1 gene. Propofol has been reported as a
      safe anaesthetic for malignant hyperthermia susceptible patients but has not been
      tested on cultured cells from patients with the ryanodine receptor type 1
      mutation. The aim of this study was to determine whether propofol could trigger
      abnormal calcium fluxes in human myotubes isolated from malignant hyperthermia
      susceptible patients harbouring the native ryanodine receptor type 1 mutation.
      Muscle specimens were obtained from the patients to diagnose malignant
      hyperthermia disposition and the calcium-induced calcium release test and
      molecular genetic analyses were performed. Using the calcium sensitive probe Fura
      2, we determined the 340/380 nm wave-length ratios by measuring alterations in
      calcium homeostasis in isolated myotubes from cultured skeletal muscle specimens.
      Two patients, one with ryanodine receptor type 1 R2508C and one with the L4838V
      mutation had accelerated calcium-induced calcium release rates. The 340/380 nm
      ratios increased when the propofol concentration exceeded 100 microM. The half
      maximal activation concentrations (EC50) for propofol from patients 1 and 2 were
      181.1 and 420.5 microM, respectively. Increases in calcium concentrations in
      response to propofol dosage were limited to doses at least 100-fold greater than
      those used in clinical settings. These observations correlate well with clinical
      observations that propofol does not trigger malignant hyperthermia in susceptible
      humans.

PMID- 18084980
TI  - The preoperative detection of risk of anaphylaxis during anaesthesia.
AB  - In 144 patients who were referred to an anaesthetic allergy clinic because of
      perceived risk of anaphylaxis during anaesthesia, the only 'at risk' group that
      could be identified was patients with a history of unexplained severe adverse
      reaction during previous anaesthesia. Twenty-two of 45 patients with such a
      history had positive skin tests to an anaesthetic drug. Twenty-one positive tests
      were to neuromuscular blocking drugs and one to an opiate. In 18 of these
      patients the medical records were available and an adverse event had been
      recorded consistent with anaphylaxis. On the contrary, investigation of patients
      without a previous adverse reaction did not appear to be of value. These findings
      suggest that those patients with a history of a severe undiagnosed adverse event
      during previous anaesthesia should be investigated with preoperative skin-testing
      before undergoing further elective surgery.

PMID- 18084981
TI  - USCOM (Ultrasonic Cardiac Output Monitors) lacks agreement with thermodilution
      cardiac output and transoesophageal echocardiography valve measurements.
AB  - The USCOM (Ultrasonic Cardiac Output Monitors) device is a non-invasive cardiac
      output monitor, which utilises transaortic or transpulmonary Doppler flow tracing
      and valve area estimated using patient height to determine cardiac output. We
      evaluated USCOM against thermodilution cardiac outputs and transoesophageal
      echocardiography valve area measurements in 22 ASA PS4 cardiac surgical patients.
      Data collection commenced following pulmonary artery catheter insertion, with
      cardiac output measurements repeated after sternotomy closure. Failure to obtain
      transaortic Doppler readings using USCOM occurred in 5% of planned measurements.
      USCOM transaortic analysis was not planned for 11 patients with known aortic
      disease. Bias at the aortic window (n = 20) was -0.79 l/min with limits of
      agreement from -3.66 to 2.08 l/min. At the pulmonary window, failure to obtain
      Doppler readings occurred in 24% of planned measurements. Bias at the pulmonary
      window (n = 36) was -0.17 l/min with limits of agreement from -3.30 to 2.97
      l/min. The USCOM estimates of valve area based on height showed poor correlation
      with the echocardiographic measurements of aortic and pulmonary valves (r = 0.57
      and r = 0.17, respectively). It was concluded that USCOM showed poor agreement
      with thermodilution. The estimated valve area was identified as one source of
      error.

PMID- 18084982
TI  - Continuous veno-venous haemofiltration attenuates myocardial mitochondrial
      respiratory chain complexes activity in porcine septic shock.
AB  - Increasing evidence indicates that mitochondrial dysfunction plays an important
      role in modulating the development of septic shock. In the present study, we
      investigated whether continuous veno-venous haemofiltration (CVVH) with high
      volume might improve myocardial mitochondrial dysfunction in a porcine model of
      peritonitis-induced septic shock. Sixteen male Landrace pigs weighing 31 +/- 5 kg
      were randomly assigned to normal control group (n = 4), peritonitis group (n = 6)
      and peritonitis plus CVVH group (n = 6). All animals were anaesthetised and
      mechanically ventilated. After baseline examinations, the peritonitis group and
      the peritonitis plus CVVH group underwent induction of peritonitis. One hour
      later, the animals in the peritonitis plus CVVH group received treatment with
      high-volume CVVH. Twelve hours after treatment, the animals were sacrificed.
      Animals in the peritonitis group were killed 13 hours after induction of
      peritonitis. Peritonitis challenge induced septic shock associated with increased
      blood lactate and high-volume CVVH improved lactate acidosis. Compared with the
      peritonitis group, cardiac output, stroke volume and mean arterial pressure were
      better maintained in peritonitis plus CVVH group. More importantly, high-volume
      CVVH improved myocardial mitochondrial complex I activity (0.22 +/- 0.03 vs. 0.15
      +/- 0.04, P = 0.04). These results suggest that high-volume CVVH improves
      haemodynamics and heart dysfunction in septic shock and the improvement may be
      attributed to amelioration of myocardial mitochondrial dysfunction.

PMID- 18084983
TI  - Propofol-induced hyperamylasaemia in a general intensive care unit.
AB  - This study examined the incidence of hyperamylasaemia, in the absence of other
      plausible causes of pancreatic dysfunction, in intensive care unit (ICU) patients
      who received propofol. One-hundred-and-seventy-two consecutive patients of a
      general ICU who stayed for more than 24 hours were studied. Patients with a
      diagnosis consistent with elevated serum amylase levels at admission were
      excluded from the study, as were patients who had received medications known to
      raise serum amylase levels. Forty-four patients 53 +/- 20 years of age and median
      duration of ICU stay of five days (range two to 55) were eligible. Thirty of
      those, aged 54 +/- 21 years and median duration of ICU stay of five days (range
      two to 27) received continuous infusion of propofol for sedation (maximum dose 45
      microg/kg/min). Of the 30 patients who received propofol, 16 (53%) developed
      hyperamylasaemia (125 to 466 IU/l) after two to nine days of continuous infusion.
      Liver and kidney function remained normal throughout the observation period. Of
      the 14 patients who did not receive propofol (aged 51 +/- 18 years), only two
      (14%) developed hyperamylasaemia, a significantly lower incidence (P = 0.021).
      Propofol infusion is associated with biochemical evidence of pancreatic injury.
      Amylase levels monitoring of propofol-sedated patients is warranted.

PMID- 18084984
TI  - A comparison of 4% succinylated gelatin solution versus normal saline in stable
      normovolaemic sheep: global haemodynamic, regional blood flow and oxygen delivery
      effects.
AB  - The objective of this study was to compare the effects on regional blood flow and
      regional oxygen delivery of 4% succinylated gelatin solution (Gelofusine, B.
      Braun) with those of normal saline. This was a randomised, controlled, cross-over
      large animal study, which took place at the animal laboratory of university
      physiology institute. The subjects were seven merino cross-ewes. We implanted
      flow probes around the aorta, coronary, renal and mesenteric arteries. We
      randomised animals to observation (control), normal saline (one litre over 15
      minutes) or Gelofusine (one litre over 15 minutes). We measured central
      haemodynamics, organ blood flows, arterial blood gases and haemoglobin every 30
      minutes for 210 minutes. Compared to control, both Gelofusine and normal saline
      significantly and similarly increased mean arterial pressure, stroke volume,
      cardiac output and central venous pressure in the first hour (P < 0.05). Such
      changes, however, were transient except for the increase in cardiac output seen
      with Gelofusine. Normal saline significantly increased mesenteric blood flow in
      the first hour (P < 0.05), while Gelofusine caused a specific, sustained and
      progressive increase in renal blood flow and conductance (P < 0.05). Both fluids
      increased urine output and creatinine clearance (P < 0.05), but, due to
      haemodilution, both decreased renal oxygen delivery in the first hour (P < 0.05).
      Normal saline and Gelofusine have transient, volume expansion-related systemic
      haemodynamic effects, which are greater for Gelofusine. Saline had a more
      pronounced early effect on mesenteric blood flow, while Gelofusine had a
      sustained and progressive greater effect on renal blood flow. The transient
      increase in urine output and creatinine clearance seen with both fluids occurred
      while renal oxygen delivery decreased.

PMID- 18084985
TI  - The influence of flushing epidural catheters before use on detection of
      intravenous placement: an in vitro and in vivo study.
AB  - Undetected intravenous placement of epidural catheters is rare but potentially
      fatal and no perfect identification method exists. Epidural catheters may be
      flushed before insertion to identify faulty epidural catheters, or to prime the
      system with local anaesthetic. We hypothesised that flushing epidural catheters
      before insertion may delay the detection of intravenous placement. We
      investigated our theory using both in vitro and in vivo models. The in vitro
      component examined flowrates in flushed and unflushed epidural catheters, using
      conditions designed to mimic epidural venous pressure. The in vivo component
      examined the flow within flushed and unflushed epidural catheters inserted into
      the forearm veins of 20 anaesthetised patients, using a randomised crossover
      design. The end-point utilised for both components was the time taken for frank
      blood to reach the 20 cm mark on the epidural catheter. Blood flow to the 20 cm
      mark on the epidural catheter was significantly faster in the unflushed catheters
      than the flushed catheters, both in vitro and in vivo (in vitro, unflushed median
      = 18.6 s (range: 18.0 to 20.5 s), flushed 37.6 s (32.6 to 91.2 s), P = 0.0009; in
      vivo, unflushed 9.2 seconds (range 5.0 to 35.3 s), flushed 19.2 s (10.6 to 47.4
      s), P = 0.003 in vivo). Flushed catheters also demonstrated a greater variability
      in the range of flowrates. Flushing epidural catheters before insertion may delay
      the detection of intravenous placement.

PMID- 18084986
TI  - Perioperative complications in patients with drug-eluting stents: a three-year
      audit at Geelong Hospital.
AB  - Drug-eluting stents are a recommended treatment for lesions in the coronary
      arteries. Stent insertion requires the patient remain on anti-platelet medication
      for a minimum of six months after insertion. A serious consequence of ceasing
      anti-platelet medication is late stent thrombosis leading to myocardial
      infarction in the territory of the drug-eluting stent. Continuing anti-platelet
      medication can lead to excessive bleeding at the time of surgery. Understanding
      the risk of complications attributable to bleeding or myocardial ischaemia will
      help in defining the optimal management of these patients at the time of non
      cardiac surgery. This study is a retrospective database analysis and case note
      review of all patients with drug-eluting stents presenting for non-cardiac
      surgical procedures over a three-year period in one centre. Twenty-four patients
      with drug-eluting stents inserted presented for 43 non-cardiac surgical
      procedures. Severe bleeding problems were encountered in one case. Three of 15
      patients (20%) who ceased clopidogrel prior to surgery without alternative anti
      thrombotic prophylaxis suffered myocardial infarction due to stent thrombosis.
      Four patients who received alternative anti-thrombotic prophylaxis did not suffer
      complications. All 19 patients who ceased clopidogrel remained on aspirin prior
      to surgery. Patients treated with drug-eluting stents for coronary artery
      stenosis represent a challenging group of patients for subsequent perioperative
      management. The risk of myocardial infarction when clopidogrel is stopped prior
      to surgery is 20%, if alternative anti-thrombotic prophylaxis is not used. This
      risk persists beyond one year after insertion of drug-eluting stents. Some
      treatments appear to be effective in reducing the risk of myocardial infarction.

PMID- 18084987
TI  - Effectiveness of superior versus inferior subconjunctival anaesthesia for
      cataract surgery.
AB  - This study compared the efficacy of two different injection sites for
      subconjunctival anaesthesia (SCA) in cataract surgery. One-hundred-and-three eyes
      of 99 consecutive patients undergoing routine cataract surgery were randomised to
      receive SCA either to the superior bulbar conjunctiva (n = 52) or the inferior
      bulbar conjunctiva (n = 51). Pain experienced during anaesthetic administration
      and at various stages of the perioperative period was assessed using a simplified
      scale. Assessment of subconjunctival haemorrhage and chemosis was made by the
      surgeon. The percentage of patients reporting any pain on administration of
      superior SCA was 46% compared to 67% with inferior SCA (P = 0.036). Moderate to
      severe pain on SCA injection was experienced by 15% and 18% of those in the
      superior and inferior SCA groups respectively. The cataract procedure was well
      tolerated in both groups. There was no difference between the groups for duration
      of surgery (P = 0.25), anaesthetic related complications including chemosis (P =
      0.28), subconjunctival haemorrhage (P = 0.38) or intraoperative complications (P
      = 0.50). We found that subconjunctival anaesthesia is effective for routine
      cataract surgery. There was no difference in block efficacy between superiorly
      and inferiorly delivered SCA. However, superior SCA appeared to be less painful
      on injection compared to inferiorly delivered SCA.

PMID- 18084988
TI  - A modified fascia iliaca compartment block has significant morphine-sparing
      effect after total hip arthroplasty.
AB  - We assessed whether a modified fascia iliaca compartment block in unilateral
      total hip arthroplasty provides a morphine-sparing effect in the first 24 hours.
      This involved a randomised, double blind study of 44 patients. Both groups
      received a modified fascia iliaca block with the trial group receiving 30 ml 0.5%
      bupivacaine with 1:200,000 adrenaline, 150 microg clonidine and 9 ml 0.9% saline
      and the control group receiving 40 ml 0.9% saline. Otherwise both groups received
      identical care with a subarachnoid block for operative anaesthesia. Patient
      controlled morphine analgesia was commenced postoperatively and data were
      collected at three, six, 12 and 24 hours post commencement of surgery. We found
      that the trial group used less morphine at 12 and 24 hours (P < 0.001). The
      median morphine usage at 24 hours was 37.5 mg in the control patients and 22 mg
      in the trial patients. Pain scores were similar between groups. We conclude that
      a modified fascia iliaca compartment block has a significant morphine-sparing
      effect in unilateral total hip arthroplasty.

PMID- 18084989
TI  - Methods of endotracheal tube placement in patients undergoing pelviscopic
      surgery.
AB  - Accidental endobronchial intubation is reported frequently during laparoscopic
      gynaecological surgery. We performed a prospective randomised study to compare
      three different methods of endotracheal tube placement in terms of susceptibility
      of accidental endobronchial intubation in patients undergoing laparoscopic
      gynaecologic surgery. The endotracheal tube was positioned by one of three
      methods: it was secured by palpating at the suprasternal notch while holding the
      pilot balloon (Group(Cuff)); by placing the 21 cm mark at the upper incisors
      (Group(21cm)); or by placing a guide mark, which was made on the surface of the
      tube 2 cm above the proximal end of the cuff at the level of the vocal cords
      (Group(VC)). The distance from the tip of endotracheal tube to the carina was
      measured with the patient in a neutral position (D(TC0)) and after the formation
      of pneumoperitoneum in the Trendelenburg position (D(TC1)). Eighty-eight patients
      were enrolled. Pneumoperitoneum and Trendelenburg position caused inward movement
      of the endotracheal tube toward the carina in 99%. In each group, the mean value
      of D(TC1) was significantly shorter than D(TC0) (Group(Cuff) 3.0 +/- 1.1 vs. 1.7
      +/- 1.0, Group(21cm) 2.5 +/- 0.8 vs. 1.1 +/- 0.9, Group(VC) 3.5 +/- 0.7 vs. 2.3
      +/- 0.8, D(TC0) vs. D(TC1) respectively) (all P < 0.01). Accidental endobronchial
      intubation occurred in 14%, with the lowest frequency in Group(VC) (2.6 %, P <
      0.01) and the highest in Group(21cm), although this was not significantly (P =
      0.09) different from Group(Cuff) (26.7% vs. 10.0%). The incidence of
      endobronchial intubation was lowest in Group(VC) but endobrochial intubation
      could not be avoided using any of these methods.

PMID- 18084990
TI  - The influence of head rotation on ProSeal laryngeal mask airway sealing during
      paediatric myringotomy.
AB  - Myringotomy with ventilation tube insertion in children involves turning the head
      from neutral to allow surgical access to the ear. In adults, rotation of the head
      from the mid-line generally increases the oropharyngeal leak pressure when a
      ProSeal laryngeal mask airway (PLMA) is used to manage the airway. There are
      concerns that these manoeuvres may distort or obstruct the paediatric airway.
      Paediatric sizes (1.5, 2.0 and 2.5) of the PLMA differ from the adult versions in
      that they do not have a dorsal cuff. This study examines the effect of these head
      position changes on the seal of the PLMA in children. Twenty-nine children (ASA 1
      2, aged 0.9 to 7.5 years) scheduled for myringotomy were recruited. After PLMA
      insertion, oropharyngeal leak pressure and fibreoptic determined PLMA position
      scores were measured in the neutral position and with head rotation of 45 degrees
      to the left or right. Fibreoptic positioning scores were similar in all
      positions. Head rotation was associated with a statistically significant but
      modest increase in oropharyngeal leak pressure versus the neutral position (P <
      0.05). After rotating the head from neutral, 38% (11 of 29) of subjects had an
      increase of oropharyngeal leak pressure of at least 2 cmH2O. Only 7% (2 of 29) of
      subjects had a decrease in oropharyngeal leak pressure with head rotation, the
      maximum decrease being 2 cmH2O. Airway obstruction did not occur in any of the
      positions. We conclude that the efficacy of the seal for the pediatric sizes PLMA
      is improved by head rotation for myringotomy.

PMID- 18084991
TI  - Critically ill children in non-paediatric intensive care units: a survey, review
      and proposal for practice.
AB  - Despite strong arguments in favour of centralising care of critically ill
      children to paediatric intensive care units, around 2000 children per year are
      cared for in non-paediatric intensive care units in Australia and New Zealand.
      This paper reports a survey of consultants from 13 such units that admitted over
      50 children in 2002 and 2003, to find out what factors affect the decision to
      keep critically ill children locally or transfer them to a paediatric intensive
      care unit and what infrastructure existed to support local care of these
      children. The results of this survey form the basis for a proposal to improve
      care of critically ill children in the non-paediatric intensive care units. The
      four key elements of this proposal are: the use of protocols, routine
      consultation with the regional paediatric intensive care unit, the use of
      telemedicine, and enhancing skills and experience of local staff Evidence
      supporting these measures as well as the evidence for centralising care of
      critically ill children is reviewed.

PMID- 18084992
TI  - Supplemental jet ventilation in conscious patients following major oesophageal
      surgery.
AB  - Intensive care unit patients are at particular risk of respiratory failure after
      major abdominal surgery. Non-invasive ventilation or application of continuous
      positive airway pressure through a face mask may stabilise respiratory function
      and avoid the need for endotracheal re-intubation. However; there are various
      contraindications to non-invasive ventilation and/or tracheal re-intubation, such
      as recent oesophageal anastomosis, anastomotic leakage or tracheal stenting for
      tracheo-oesophageal fistula. A specific management strategy consisting of
      continuous intratracheal jet ventilation to support spontaneous respiratory
      function is described in two patients with contraindications to non-invasive
      ventilation or mask continuous positive airway pressure after major oesophageal
      surgery.

PMID- 18084993
TI  - Missed foreign body and nessitans empyema.
AB  - A recurrent empyema over a three-month period ultimately presented as an empyema
      necessitans (an empyema pointing through the skin) due to Fusobacterium varium.
      The recurrence of the empyema was due to an animal vertebra aspirated, during a
      bar-room altercation, into the right main bronchus, mimicking an endobronchial
      tumour.

PMID- 18084994
TI  - Severe acute respiratory distress syndrome in pregnancy. Caesarean section in the
      second trimester to improve maternal ventilation.
AB  - We report the case of a 25-year-old woman in the second trimester of pregnancy
      with acute respiratory distress syndrome associated with miliary tuberculosis.
      Delivery of the baby by caesarean section at 24 weeks gestation resulted in an
      immediate and sustained improvement in respiratory function and maternal
      survival. We believe this to be the first report suggesting a role for caesarean
      section, performed with the aim of an improvement in maternal respiratory
      function, at such an early point in pregnancy.

PMID- 18084995
TI  - The management of a super morbidly obese parturient delivering twins by caesarean
      section.
AB  - A super morbidly obese (230 kg, body mass index 76 kg/m2) patient presented to
      our service for a planned elective caesarean section for twin delivery. She
      subsequently underwent a non-elective caesarean section after normal working
      hours under combined spinal epidural anaesthesia with invasive monitoring.
      Complex cases such as this, especially in the obstetric setting, require thorough
      multidisciplinary planning, communication and expertise but can be safely and
      successfully performed in dedicated stand-alone centres.

PMID- 18084996
TI  - Bilaterally absent pupillary responses: not always a bad sign.
AB  - Pupillary responses are a simple test commonly used as a predictor of outcome
      after severe brain injury. It is also common for clinicians to associate
      bilaterally absent pupillary responses with very poor prognosis. We report a
      series of cases of severely brain injured children with bilaterally absent
      pupillary responses who had favourable outcomes. From a group of 89 patients with
      brain injury, 32 had bilaterally absent pupillary responses and six (four with
      traumatic brain injury and two with infective brain injury) subsequently had
      favourable outcomes. This represents 18.8% of patients and should be a reminder
      to clinicians that the clinical sign of bilaterally absent pupillary responses is
      not always associated with a hopeless outcome.

PMID- 18084997
TI  - Estimating oxygenation in methaemoglobinaemia.

PMID- 18084998
TI  - Effect of nitric oxide on oxygenation in lung injury after surgery for ruptured
      abdominal aneurysm.

PMID- 18084999
TI  - Intraoperative hyperglycemia in a child with primary pancreatic lymphoma.

PMID- 18085000
TI  - Fractured spike of needle-less InterLink Vial Access Cannula.

PMID- 18085001
TI  - New source of leak on Aestiva/5 anaesthesia machine.

PMID- 18085002
TI  - Voices that changed psychoanalysis in unpredictable ways.

PMID- 18085003
TI  - Analysis of the therapeutic factors in psychoanalytic treatment. 1950.

PMID- 18085004
TI  - Alexander's corrective emotional experience: an objectivist turn in
      psychoanalytic authority and technique.

PMID- 18085005
TI  - Commentary on Franz Alexander's "analysis of the therapeutic factors in
      psychoanalytic treatment".

PMID- 18085006
TI  - Internalization, separation, mourning, and the superego. 1962.

PMID- 18085007
TI  - The psychoanalyst as a new old object, an old new object, and a brand new object:
      reflections on Loewald's ideas about the role of internalization in life and in
      psychoanalytic treatment.

PMID- 18085008
TI  - A letter to Hans Loewald.

PMID- 18085009
TI  - The same and the identical. 1970.

PMID- 18085010
TI  - A plea for a broader concept of Nachtraglichkeit.
AB  - The broader conceptualization of Nachtraglichkeit proposed by the author can play
      an active part in the process of assigning new meaning retroactively (usually
      through interpretation)--and even giving a meaning, for the first time (usually
      through construction)--to what the analysand says and cannot say. It gives us a
      conceptual frame of unconscious psychic temporality with which to explore how
      psychoanalysis produces psychic change. Winnicott's "Fear of Breakdown" (1974) is
      paradigmatic of this broader conceptualization of Nachtraglichkeit (see Faimberg
      1998). A clinical example is presented (Kardiner 1977) to illustrate why the
      author believes that her proposal remains true to Freud's (1937) conception of
      psychic temporality and construction.

PMID- 18085011
TI  - Seduction and the vicissitudes of translation: the work of Jean Laplanche.
AB  - This paper aims to analyze Jean Laplanche's revision of Freudian metapsychology,
      which emerged from a critical return to Freud's officially abandoned seduction
      theory of 1895-1897. Where Freud gradually replaced the model of traumatic
      seduction with a theory of infantile sexuality and its drives, Laplanche
      articulates both trauma and sexual drive in a new theory of primal seduction, the
      fundamental anthropological situation in which human subjectivity is formed. The
      author concludes by considering Laplanche's modeling of the psychoanalytic
      situation and his reformulation of transference in relation to mourning and
      sublimation within the framework of the general theory of seduction.

PMID- 18085012
TI  - Panic as a form of foreclosed experience.
AB  - Following a discussion of panic states and their relationship to psychosomatic
      illness and related disorders, the author presents an extended clinical vignette
      in which he initially viewed the patient's intense anxiety as a manifestation of
      repressed conflict and, accordingly, used verbal interpretations as the principal
      mode of intervention. After this approach did not prove effective, the analyst
      began to make use of nonverbal interventions consistent with his emerging
      understanding of the patient's distress as a manifestation of the foreclosure (de
      M'Uzan 2003) and relegation to the body of undreamable experience (Bion 1962).

PMID- 18085013
TI  - Actual neurosis as the underlying psychic structure of panic disorder,
      somatization, and somatoform disorder: an integration of Freudian and attachment
      perspectives.
AB  - Starting from a contemporary critique of the DSM-IV, this paper argues that the
      diagnostic categories of panic disorder somatization, and undifferentiated
      somatoform disorders can be understood as belonging to a common type of
      psychopathology--i.e., the Freudian actual neuroses. In addition to their strong
      clinical similarity, these disorders share an etiological similarity; and the
      authors propose a combination of Freud's focus on this type of patient's
      inability to represent an endogenous drive arousal with the post-Freudian focus
      on separation anxiety. An etiological hypothesis is put forward based on
      contemporary psychoanalytic attachment theory, highlighting mentalization.
      Concrete implications for a psychoanalytically based treatment are proposed.

PMID- 18085014
TI  - The dreaded promise of Christmas and the New Year.
AB  - For many patients, mixed feelings of promise and dread that can accompany the
      holiday season appear in consciousness faintly and fleetingly, usually in the
      form of bad expectations. But the "dreaded promise" (an oxymoron) of change can
      come to full life and is always potentially present, especially at separations,
      and is usually perceptible by the analyst. The dread can be accompanied by
      expectations full of wonderful promise. The promise of Christmas is followed by
      the promise of New Year's Day--a time for new beginnings and resolutions aimed at
      changes for the better. But, for some, happy expectations evoking change have in
      the past been succeeded by bad ones, and the revival of predominant dread can be
      cruel and repetitive.

PMID- 18085015
TI  - A variant of joking in dreams.

PMID- 18085016
TI  - A pun in a dream.

PMID- 18085017
TI  - Smoking, self-destructive behaviour?

PMID- 18085018
TI  - Macrolide therapy of chronic rhinosinusitis.
AB  - There is growing evidence that several antibiotics exert their beneficial effect
      not only by inhibiting or killing bacterial pathogens but also by down-regulating
      pro-inflammatory mechanisms. This review aims to give an overview of the
      immunomodulatory properties of macrolide antibiotics in chronic rhinosinusitis
      and to present a treatment algorithm for managing the difficult CRS patient with
      long-term, low-dose macrolide antibiotics. The most prominent effect of
      macrolides noted in vitro is the inhibition of pro-inflammatory cytokines such as
      interleukin-8. This effect is probably secondary to inhibition of the activation
      of transcription factor NF-kappaB. As a result an attenuation of neutrophilic
      inflammation takes place. Moreover, macrolides inhibit bacterial virulence and
      biofilm formation. In vivo, a reduction of pro-inflammatory cytokines is evident
      in nasal lavage as well as a reduction in nasal secretions. The clinical effect
      is shown in less facial pain, less headache, less post nasal drip, fewer
      exacerbations of sinusitis and improved quality of life. The treatment should be
      targeted towards the non-atopic patients with bilateral disease whereas in
      unilateral disease, surgery is the first option. Macrolide resistant bacterial
      strains have to be monitored, but to date they have not been of clinical
      importance.

PMID- 18085019
TI  - Impact of gender, age, and comorbidities on quality of life in patients with
      chronic rhinosinusitis.
AB  - STATEMENT OF THE PROBLEM: To evaluate the impact of gender, age and comorbidities
      of health-related quality of life (HR-QOL) assessments in patients with chronic
      rhinosinusitis. METHODS: The prospective administration of the German Adapted
      Version of the Sino-Nasal Outcome Test 20 (SNOT-20 GAV) to patients with chronic
      rhinosinusitis. Two hundred and two patients with chronic rhinosinusitis filled
      out the questionnaire before functional endoscopic sinus surgery (FESS) and again
      at the 3-month follow-up. MAIN RESULTS: Gender had a significant impact on the
      Overall Score (OS) and on the General Quality of Life Score (GQOL) of the SNOT-20
      GAV but no influence on the disease-specific scores of 'Primary Nasal Symptoms'
      (PNS) and 'Secondary Rhinogenous Symptoms' (SRS). Age did not influence HR-QOL.
      Patients with comorbidities demonstrated lower HR-QOL scores. PRINCIPAL
      CONCLUSION: Women had significantly poorer QOL scores than men. It seems that the
      influence of gender reflects general HR-QOL views rather than illness-related
      expectations.

PMID- 18085020
TI  - The effect of smoking on the olfactory function.
AB  - Although smoking is a widely spread habit, its effect on olfaction has not been
      clearly established. The aim of this study was to investigate the effect of
      cigarette smoking on the olfactory function, using the "Sniffin' Sticks" test.
      Sixty-five smokers were studied, with a median period of smoking of 10 years
      (range: 1-45 years) and a median number of 15 cigarettes smoked per day (range: 5
      20). Forty-nine non-smokers were used as controls. Olfactory function was
      evaluated using the "Sniffin' Sticks" test, which consists of odour threshold
      (OT), odour discrimination (OD) and odour identification (OI) and its overall
      results may be presented as a composite threshold-discrimination-identification
      (TDI) score. Multivariate linear and logistic regression analyses were performed.
      All OT, OD, OI and TDI scores were statistically significantly lower in smokers
      compared to non-smokers, even when controlled for gender and age. Low OT, OD, OI
      and TDI scores were more prevalent among smokers than non-smokers. Multivariate
      logistic regression analysis, adjusted for gender and age, revealed that smoking
      remained a strong independent risk factor for low OT, OD, OI and TDI scores.
      Among smokers, statistically significant negative relationships were found
      between pack-years and OT, OD, OI and TDI, controlling for age. In conclusion,
      smoking was found to be adversely associated with the olfactory ability in a dose
      related manner. Smokers were found to be nearly six times as likely to evidence
      an olfactory deficit as non smokers, depending on the duration and the amount of
      cigarettes smoked.

PMID- 18085021
TI  - Surface laser registration in ENT-surgery: accuracy in the paranasal sinuses--a
      cadaveric study.
AB  - Over the past decade, surgical navigation systems have found widespread use in
      ENT-surgery. Navigational accuracy highly depends on the registration process.
      The objective of this study was to assess the accuracy in the paranasal sinuses
      and lateral skull base after surface laser registration using the navigation
      system VectorVisionCompact (BrainLab, Heimstetten, Germany). Repeated
      measurements were performed on two cadaver heads. Sixteen titanium screw
      fiducials per head were placed in facial bones, the paranasal sinuses and the
      lateral skull base, thereby serving as exactly identifiable measurement points.
      The respective influence on measurement accuracy depending on the localization
      and conformation of the registration area was evaluated by performing
      symmetrically bilateral as well as strictly unilateral registrations. The
      resulting overall accuracy for a symmetrically bilateral surface laser
      registration was 1.13 +/- 0.53 mm, ranging from 0.77 (sinus frontalis) to 1.76
      (petrous bone) mm, and thus proved to be clinically sufficient. Increasing
      distance between target point and registration area went along with a decline in
      accuracy. Navigational accuracy was significantly influenced by the choice of the
      registration area. Best accuracy was detected after symmetrically bilateral
      registration.

PMID- 18085022
TI  - Association of allergy, asthma and IgE sensitisation to adenoidectomy and
      infections in children.
AB  - OBJECTIVE: To find out whether previous adenoidectomy is associated with asthma,
      allergic symptoms or allergen-specific IgE antibodies. RECRUITMENT AND METHODS:
      We recruited 213 paediatric patients admitted for elective tonsillectomy and 155
      paediatric controls. Using a structured questionnaire, we recorded their
      respiratory symptoms, allergies, bronchial asthma and environmental factors.
      Serum IgE antibodies against respiratory allergens were screened. Patients were
      divided into those previously adenoidectomised (n = 100) or not adenoidectomised
      (n = 113). RESULTS: Any allergy (p = 0.007) and non-antibiotic allergy diagnosed
      by a doctor (p = 0.015), and asthma (p = 0.015) were more common among
      adenoidectomised than non-adenoidectomised children under the age of seven.
      Between ages 7 and 11, neither any kind of allergy nor asthma were associated
      with earlier adenoidectomy. In the oldest age group (12 to 17), only antibiotic
      allergy was more common in adenoidectomised children. Recurrent otitis media (p <
      0.001) and recurrent sinusitis (p = 0.007) were more common in adenoidectomised
      children. After controlling for recurrent respiratory infections, doctor
      diagnosed allergy remained significantly associated with adenoidectomy in the
      youngest age group. Prevalence of specific IgE did not differ between the patient
      groups, or between school-aged patients and controls. CONCLUSIONS: Our results
      suggest that hypersensitivity disorders and infections may share aetiological
      factors. However, as adenoidectomised children of any age did not have higher
      levels of specific IgE, it seems possible that allergy is either clinically over
      diagnosed or insufficiently detected by serology among young adenoidectomised
      children.

PMID- 18085023
TI  - Swine dust exposure is a model for rapid induction of non-allergic neutrophil
      inflammation in the nasal mucosa of healthy volunteers, and the symptoms as well
      as the microcirculation are modified by nasal lavage.
AB  - BACKGROUND: The pathophysiological mechanism of non-allergic rhinitis is not
      clear and there is a lack of models in healthy volunteers. It has previously been
      shown that swine dust exposure is an excellent method for inducing inflammatory
      changes in the lower airways. We have shown earlier that exposure to swine dust
      increases the histamine sensitivity of the nasal mucosa as measured by
      rhinostereometry. In this study the aim was to investigate the effects of swine
      dust exposure on nasal symptoms as well as the microcirculation. Furthermore, the
      effect on nasal lavage was investigated. METHOD: Seventeen subjects were exposed
      to swine dust during a three-hour period of work in a swine house. Nasal symptoms
      and the nasal mucosal response to histamine before and after exposure to swine
      dust were evaluated by laser Doppler flowmetry and nasal lavage. RESULTS:
      Exposure to swine dust increased nasal symptoms and levels of neutrophils, IL-8
      and albumin. The increase in nasal symptoms and the microcirculation were
      modified by nasal lavage. CMBC correlated inversely with an increase in albumin
      (p = 0.018, R = -0.95). CONCLUSIONS: Swine dust exposure is a useful model for
      inducing nasal inflammation in healthy volunteers. Furthermore, nasal lavage
      modifies subjective as well as objective parameters, which should be considered
      when designing studies. Nasal lavage may be useful in the treatment of workers in
      a swine dust environment.

PMID- 18085024
TI  - Nasal manifestations of self-destructive behaviour.
AB  - Self-destructive behaviour is prevalent in a variety of different psychiatric
      disorders. Most common manifestations are self-inflicted cuts to the skin,
      especially the skin of the forearms. Manifestations of self-destructive behaviour
      involving the nasal area are rather rare. A series of cases is presented in which
      nasal diseases were initially misinterpreted, but could finally be identified as
      factitious disorders. Presented symptoms were foreign body insertions,
      hemodynamically relevant epistaxis and impetiginous inflammations of the
      paravestibular skin of the nose. Factitious disorders of the nose should be
      identified as such for the following reasons: avoiding unnecessary operations,
      adequate symptomatic rhinologic therapy and the initiation of psychiatric
      consultation.

PMID- 18085025
TI  - Incidence of CSF fistula after paranasal sinus surgery: the Northern Norwegian
      experience.
AB  - STATEMENT OF PROBLEM: Cerebrospinal fluid (CSF) fistula is a well-known
      complication of paranasal sinus surgery. Not only manifest, but also occult CSF
      fistulas occur. The incidence of occult CSF fistula has been described only once
      and has not been tested since. MATERIAL AND METHODS: In a prospective diagnostic
      study, the incidence of manifest and occult CSF fistulas was measured. Forty four
      patients operated for paranasal sinus diseases were included between 2002 and
      2006. Seventy four fluid samples were collected by pressing nasal tamponades the
      day after surgery, and were measured for beta-trace protein using laser
      nephelometry. In patients with a beta-trace value in secretion between 0.68 and
      1.11 mg/l, a serum sample was taken and measured for beta-trace protein. RESULTS:
      Thirty-one patients had a secretion beta-trace protein value below 0.68 mg/l.
      Thirteen patients had a secretion beta-trace protein value between 0.68 and 1.11
      mg/l. The secretion/serum ratio in this group was below 1.57, not indicating the
      presence of CSF traces. The incidence of CSF fistula in this study population was
      zero. PRINCIPAL CONCLUSION: A previously described incidence of occult CSF
      fistula after paranasal sinus surgery was not confirmed in the present study.

PMID- 18085026
TI  - Endoscopic surgery reveals that woodworkers' adenocarcinomas originate in the
      olfactory cleft.
AB  - The olfactory cleft is a narrow chamber located under the cribriform plate and
      between the turbinate wall of the ethmoidal labyrinth and the corresponding nasal
      septum. Nasal adenocarcinomas are mostly described as originating in the ethmoid
      sinus and operated via external approaches. We designed a prospective study on
      twenty consecutive woodworkers' adenocarcinomas without intracranial extension to
      determine the precise site of origin of the tumour. All patients were operated
      under endoscopic endonasal control according to a methodical surgical procedure
      as follows: 1) debulking of the tumour and identification of the middle turbinate
      or conchal lamina, 2) exenteration of the ethmoidal labyrinth according to the
      nasalisation procedure, and 3) exenteration of the olfactory cleft. Endoscopic
      endonasal surgery showed that woodworkers' adenocarcinomas constantly originated
      in the olfactory cleft, appearing as polyp-like neoplasms with well-defined
      bodies. Over a long period of time, they do not invade, but just displace and
      push out the surrounding structures, i.e. the nasal septum and the turbinate
      wall. More than the volume of the tumour, the precise location of the pedicle and
      especially its connection to the cribriform plate could be of major prognosis
      value.

PMID- 18085027
TI  - Frontal sinus osteomas: the window of endonasal endoscopic approach.
AB  - OBJECTIVE: Management of symptomatic osteomas involving the frontal sinus is
      challenging. Traditional external approaches have been used in the surgical
      management of these lesions. Recently, endonasal endoscopic surgery has become a
      valid alternative to the traditional external approach in selected cases. METHOD
      OF STUDY: Retrospective evaluation of the patients with symptomatic fronto
      ethmoidal osteomas surgically managed in the last 10 years at a tertiary care
      facility. RESULTS: Twenty-six osteomas involving the frontal sinus were treated
      surgically. In 11 cases a purely endoscopic approach was performed while in 13
      patients a combined procedure was used. In two patients, an exclusively external
      procedure was performed. No osteoma recurrence has been observed yet (mean follow
      up: 40 +/- 31.75 SD months). CONCLUSIONS: Endonasal endoscopic resection of a
      frontal sinus osteoma is feasible when the lesion is medial to a virtual plane
      through the lamina papyracea and is attached in the lower portion of the
      posterior wall of the frontal sinus.

PMID- 18085028
TI  - The effect of prilocaine and prilocaine plus meperidine infiltration on the pain
      during nasal packing removal.
AB  - OBJECTIVE: Removing the nasal packing after nasal surgery is an uncomfortable and
      painful procedure. Since there is no controlled trial described in the literature
      about the local use of meperidine during packing removal, we aimed to compare the
      analgesic and sedative effects of the meperidine-prilocaine combination, injected
      into the packing 15 minutes before the procedure, with that of prilocaine during
      packing removal. METHODS: Fifty adult patients, for whom nasal packing removal
      after nasal septoplasty was scheduled, were randomly allocated into one of two
      groups. In the prilocaine group (Group P, n = 25), 5 ml of 1% prilocaine in
      saline was injected into the pack 15 minutes before removal. In the prilocaine
      meperidine group (Group MP, n = 25), 5 ml fluid combination containing prilocaine
      (10 mg/ml) and meperidine (1 mg/kg) was injected in nasal packs. Five ml saline
      was injected into the package in the contra-lateral nostril in both groups as
      control. Visual analogue scale (VAS) score was recorded during injections (t) and
      packing removal (t), and the Ramsay sedation score was evaluated. RESULTS: VAS
      score was not different from the control nostril in Group P (p > 0.05), where as
      it was significantly lower than the control nostril in Group MP (p < 0.05).
      Ramsay sedation scores were significantly higher in Group MP compared to the
      control nostril and actively treated nostril of Group P (p < 0.05). CONCLUSION:
      The injection of prilocaine plus meperidine into the nasal pack 15 minutes before
      nasal packing removal provides effective analgesia and mild sedation during the
      procedure.

PMID- 18085029
TI  - Porous polyethylene implants in revision rhinoplasty: chances and risks.
AB  - INTRODUCTION: High density Polyethylene (PE) is a chemically pure, porous plastic
      implant material that can perform supportive functions. The material has good
      tissue biocompatibility and permits ingrowth of connective tissue with related
      vascularization. The material is being used more frequently in nasal surgery. In
      this study we describe possibilities and limitations in the use of PE in rhino
      surgery. MATERIAL AND METHODS: Thirty-two charts of patients with rhinoplasty and
      PE-implantation were reviewed. All patients were seen in our department again. A
      database was created which included the following parameters: date and exact area
      of implantation, shape and thickness of the implant, number of revisions,
      technique of prior rhinoplasties, complications and the patients' satisfaction.
      RESULTS: Seventy-five percent of patients were revision rhinoplasties at the time
      of surgery. Seven out of thirty two (21%) patients developed a complication. In
      four cases, the complication was managed with total explantation; three patient's
      condition required partial explantation. The shortest implantation period was
      only 24 days and the longest lasting implant within the complication group was
      explanted 266 days after implantation. All these patients had undergone multiple
      rhinoplasties before, with heavy scar tissue and septal perforations. The most
      frequent complication (n = 4) was a partially extruded implant without any signs
      of infection in the area of the anterior septum. DISCUSSION: Our descriptive
      study shows limitations in the use of PE for rhinoplasty. It seems crucial that
      the implant is completely covered with vital tissue, otherwise vascularization
      and healing is excluded. The implantation place should be vital and without any
      signs of infection. The covering tissue should not be too thin or scarred. An
      early infection of the open porous system prevents vascularization and healing
      and inevitably causes a rejection. The reason for the high complication rate (>
      20%) in this study lies in the specifications of the selected patient group at
      hand. All implantations were performed in seriously damaged scar tissue after
      multiple revision rhinoplasties. Due to the results of our evaluation we can
      recommend the use of PE: 1. in a vital, healthy implant site; 2. with small
      material that can be embedded totally and without tension; 3. in primary
      rhinoplasty or with only little scar tissue.

PMID- 18085030
TI  - Traumatic internal carotid artery pseudoaneurysm mimicking sphenoid sinus tumor.
AB  - Massive epistaxis following blunt craniofacial trauma should alert clinicians to
      possible traumatic internal carotid artery (ICA) aneurysm. This article describes
      a case of a 46-year-old female patient with traumatic ICA pseudoaneurysm
      presenting similar to a sphenoid sinus mass lesion. Massive bleeding occurred
      during the endoscopic procedure. Brain angiography revealed two lobulated ICA
      pseudoaneurysms over a cavernous segment. The patient successfully underwent
      endovascular stent assisted coil embolization. Timely diagnosis and treatment of
      the ICA psuedoaneurysm produced a favourable outcome.

PMID- 18085031
TI  - Clinical decision support systems for addressing information needs of physicians.
AB  - Clinicians routinely practice in a state of incomplete information--about the
      patient, and about medical knowledge pertaining to patients' care. Consequently,
      there is now growing interest in the use of CDSS to bring decision support to the
      point of care. CDSS can impact physician behavior in routine practice.
      Nonetheless, CDSSs are meant to support humans who are ultimately responsible for
      the clinical decisions, rather than replace them. Although the adoption of CDSS
      has proceeded at a slow pace, there is a widespread recognition that CDSSs are
      expected to play a crucial role in reducing medical errors and improving the
      quality and efficacy of health care. This will be facilitated by the gradual
      maturation of electronic health record systems and the emergence of standard
      terminologies and messaging standards for the exchange of clinical data.

PMID- 18085032
TI  - Implementing presumed consent for organ donation in Israel: public, religious and
      ethical issues.

PMID- 18085033
TI  - Primary care screening for childhood obesity: a population-based analysis.
AB  - BACKGROUND: The prevalence of obesity among children and adolescents in the
      western world has increased dramatically. OBJECTIVES: To assess the efficacy of
      routine childhood obesity screening by primary physicians in the pediatric
      population in Israel and the utilization of health services by overweight
      children. METHODS: The electronic medical records of children aged 60-83 months
      registered in 39 pediatric primary care centers between January 2001 and October
      2004 (n=21,799) were reviewed. Those in whom height and weight were documented
      during a clinic visit (index visit) were classified as overweight, at risk of
      overweight, or normal weight according to body mass index percentiles. The number
      of visits to the pediatrician, laboratory tests and health care costs 12 months
      after the index visit were calculated. RESULTS: Anthropomorphic measurements were
      performed in 1556 of the 15,364 children (10.1%) who visited the clinic during
      the study period. Of these, 398 (25.6%) were overweight, 185 (11.9%) were at risk
      of overweight, and 973 (62.5%) were normal weight. Children in the first two
      groups visited the clinic slightly more often than the third group, but the
      differences were not statistically significant (P = 0.12), and they had
      significantly more laboratory tests than the rest of the children visiting the
      clinics (P = 0.053). Health care costs were 6.6% higher for the overweight than
      the normal-weight children. CONCLUSIONS: Electronic medical records are a useful
      tool for population-based health care assessments. Current screening for obesity
      in children during routine care in Israel is insufficient and additional
      education of community pediatricians in diagnosis and intervention is urgently
      needed.

PMID- 18085034
TI  - Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy in peritoneal
      carcinomatosis.
AB  - BACKGROUND: Peritoneal carcinomatosis is an advanced form of cancer with poor
      prognosis that in the past was treated mainly palliatively. Today, the definitive
      approach to peritoneal surface malignancy involves peritonectomy, visceral
      resection and perioperative intra-abdominal hyperthermic chemotherapy. The
      anticipated results range from at least palliative to as far as intent to cure.
      Proper patient selection is mandatory. OBJECTIVES: To determine whether
      cytoreductive surgery and intraperitoneal hyperthermic chemotherapy can extend
      survival, and with minor complications only, in patients with peritoneal
      carcinomatosis. METHODS: Twenty-two IPHP procedures were performed in 17 patients
      with peritoneal carcinomatosis in our institution between 1998 and 2007: 6 had
      pseudomyxoma peritonei, 5 had colorectal carcinoma, 3 had ovarian cancer and 3
      had mesotheliomas. All patients underwent cytoreductive surgery, leaving only
      residual metastasis < 1 cm in size. Intraperitoneal chemotherapy was administered
      through four large catheters (2F) using a closed system of two pumps, a heat
      exchanger and two filters. After the patient's abdominal temperature reached 41
      degrees C, 30-60 mg mitomycin C was circulated intraperitoneally for 1 hour.
      RESULTS: The patients had a variety of anastomoses. None demonstrated anastomotic
      leak and none experienced major complications. Six patients had minor
      complications (pleural effusion, leukopenia, fever, prolonged paralytic ileus,
      sepsis), two of which may be attributed to chemotherapy toxicity (leukopenia).
      There was no perioperative mortality. Some patients have survived more than 5
      years. CONCLUSIONS: IPHP is a safe treatment modality for patients with
      peritoneal carcinomatosis. It has an acceptable complications rate and ensures a
      marked improvement in survival and in the quality of life in selected patients.

PMID- 18085035
TI  - Germline CHEK2 mutations in Jewish Ashkenazi women at high risk for breast
      cancer.
AB  - BACKGROUND: Germline mutations in BRCA1 and BRCA2 genes account for only 20-40%
      of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase,
      involved in response to DNA damage, and hence is a candidate gene for breast
      cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was
      reported in a subset of mostly North European breast cancer families. The rate of
      the CHEK2*1100delC variant in the Ashkenazi Jewish population was reported to be
      0.3%. OBJECTIVES: To evaluate whether CHEK2 germline mutations contribute to a
      breast cancer predisposition in Ashkenazi** Jewish high risk families. METHODS:
      High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant
      Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the
      CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing
      gradient gel electrophoresis and sequencing of abnormally migrating fragments.
      RESULTS: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast
      cancer (average age at diagnosis 49.6 +/- 9.6 years, mean +/- SD) and 97
      asymptomatic individuals (age at counseling 48.3 +/- 8.2 years). No truncating
      mutations were noted and four previously described missense mutations were
      detected (R3W 1.2%, 1157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism
      (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis
      of the 1157T and S428F mutations (shown to affect protein function) with the
      cancer phenotype showed concordance for the CHK2*1157T mutation, as did two of
      three families with the CHK2*S428F mutation. CONCLUSIONS: CHEK2 missense
      mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

PMID- 18085036
TI  - Open access gastroscopy in hospitalized patients.
AB  - BACKGROUND: Open access gastroscopy allows physicians to refer patients for
      endoscopic procedures without a prior consultation. OBJECTIVES: To compare the
      safety and efficacy of OAG with gastroscopy performed after a gastroenterological
      consultation. METHODS: Patients referred for gastroscopy directly (open access)
      or after consultation with a gastroenterologist, by physicians in the departments
      of internal medicine and surgery at a major tertiary center, were compared for
      indications, background disease, outcome and diagnostic yield. The data were
      collected prospectively over a 5 month period following the introduction of OAG
      at the center. Physicians in both departments participated in an education
      program on the indications and procedure of gastroscopy. For each patient
      referred for OAG the attending physician completed a specially designed
      questionnaire that had to be signed by a senior physician. Data were managed and
      analyzed with Excel and SPSS software. RESULTS: The study sample comprised 494
      patients, of whom 236 were referred for OAG and 258 after prior consultation. On
      multivariate analysis, hospitalization in the department of internal medicine was
      the only independent factor for OAG. Severe background disease and aspirin
      treatment had no effect on physician use of OAG, although they served as a "red
      light" for the gastroenterology consultants. There was no difference in the
      diagnostic yield of the procedures (26.4% normal findings for OAG and 28.3% for
      consultations) or in mortality rates. The main indications for referral to
      gastroscopy in the surgery department were melena, hematemesis and "coffee
      grounds," and anemia and vomiting in the internal medicine department.
      CONCLUSIONS: OAG is feasible and beneficial in an academic medical center
      setting, with no bias in appropriateness of indications or decrease in the
      diagnostic yield compared to the traditional approach. More attention should be
      directed to safety issues by the referring physicians.

PMID- 18085037
TI  - Prevalence of chronic obstructive pulmonary disease among smokers aged 45 and up
      in Israel.
AB  - BACKGROUND: Chronic obstructive pulmonary disease is an increasing cause of
      chronic morbidity and mortality around the world. The major cause of the disease
      is smoking. Despite the gravity of the problem there is no knowledge of its rate
      in the Israeli smoking population. OBJECTIVES: To assess the prevalence of COPD
      and early lung cancer among smokers. METHODS: People aged 45 up to 75 with a
      history of at least 20 pack-years cigarette smoking, including quitters, were
      screened for COPD. They were interviewed and a spirometry was performed. RESULTS:
      Of the 1150 people recruited 92% underwent and performed acceptable spirometry;
      22% of these subjects had airflow limitation and were diagnosed with COPD
      according to the GOLD classification. Only 4% had been diagnosed as COPD prior to
      this screening. The majority of those tested were unaware of or unconcerned about
      developing the disease. There was no correlation between pack-years smoking and
      development of COPD, but there was a relative correlation of pack-years smoking
      and severity of COPD, particularly in the older group (r = 0.42). CONCLUSIONS:
      About one-fifth of the smokers aged 45 and up developed COPD. There is a
      significant gap between the disease distribution and its awareness in the
      population at risk. The need for a national screening program and early diagnosis
      of COPD in people at risk is needed.

PMID- 18085038
TI  - Ten years surveillance of antimicrobial susceptibility of community-acquired
      Escherichia coli and other uropathogens in northern Israel (1995-2005).
AB  - BACKGROUND: In an era of increasing antimicrobial resistance, knowledge of local
      antimicrobial susceptibility patterns of common uropathogens is essential for
      prudent empiric therapy of community-acquired urinary tract infections.
      OBJECTIVES: To define antimicrobial susceptibility of Gram-negative uropathogens
      in northern Israel over a 10 year period and to compare it with patterns of
      antibiotic use in the same community. METHODS: We tested the susceptibility of
      all Gram-negative urinary isolates from outpatients at HaEmek Medical Center over
      the years 1995, 1999, 2002 and 2005 to common antimicrobial agents. MIC90 of
      Escherichia coli to some of these agents was determined and antibiotic
      consumption data over the years 2000-2005 (DDD/1000/day) were obtained. RESULTS:
      We observed a rise in susceptibility rates of E. coli to amoxicillin-clavulanate,
      trimethoprim-sulfamethoxazole and nitrofurantoin and of other Gram-negative
      isolates to amoxicillin-clavulanate, ceftriaxone and cephalothin. Susceptibility
      rates of all Gram-negative uropathogens to ciprofloxacin decreased significantly.
      MIC90 of E. coli for all drugs tested remained stable. There was a significant
      decrease in the use of nitrofurantoin and TMP-SMX and a significant increase in
      the use of ampicillin, cephalothin and ceftriaxone. CONCLUSIONS: Antibiotic
      resistance patterns mostly remained unchanged or improved slightly. There was,
      however, a constant decrease in susceptibility of all Gram-negative uropathogens
      to ciprofloxacin. Antibiotic use patterns could not explain the changes seen in
      antibiotic susceptibility patterns.

PMID- 18085039
TI  - Effects of rehabilitation winter camps at the Dead Sea on European cystic
      fibrosis patients.
AB  - BACKGROUND: Rehabilitation camps can improve exercise tolerance and nutrition in
      cystic fibrosis patients. OBJECTIVES: To assess weight gain, pulmonary function
      tests and daily symptoms in European CF patients attending a rehabilitation camp
      at the Dead Sea, Israel. METHODS: We conducted a retrospective study assessing 94
      CF patients who participated in winter camps held at the Dead Sea, Israel from
      1997 to 2000. The camp program included daily physiotherapy, physical activities,
      and a high caloric diet. We assessed weight gain, pulmonary function tests,
      oxyhemoglobin saturation and daily symptoms before (pre), on departure (dep), and
      up to 3 months after the 3 week rehabilitation camp (post). All data were
      analyzed by ANOVA for repetitive measurements. P < 0.05 was considered
      significant. RESULTS: Lung function tests and oxyhemoglobin saturation taken
      before, on departure and 3 months after camp were available for 35 patients.
      Forced expiratory volume in the first second (% predicted, average +/- SD)
      improved by 8.2 +/- 2.3% (pre, dep, post, P < 0.05). Oxyhemoglobin saturation
      mildly improved (1 +/- 0.3%, pre, dep, post, P < 0.05). Forced vital capacity (%
      predicted) increased by 3.9 +/- 1.2%, but was not significant (P = 0.19). Total
      body weight of 89 patients improved by 1.9 +/- 0.9% during the camp time (P <
      0.05, t-test), and in a group of 24 patients weight continuously increased up to
      5.0 +/- 1.7% at 3 months after the camp (P = 0.004, ANOVA). CONCLUSIONS: In this
      attrition-limited retrospective study, European CF patients improved their
      pulmonary function and gained weight during and up to 3 months after a 3 week
      rehabilitation winter camp at the Dead Sea, Israel.

PMID- 18085040
TI  - A histopathological review of gastrointestinal related mesenchymal tumors: the
      hidden GIST.
AB  - BACKGROUND: The diagnosis of gastrointestinal stromal tumors is based on
      documentation of c-KIT and platelet-derived growth factor-alpha receptors or
      specific c-KIT mutations. Before the diagnosis of GIST was possible, all cases
      had been classified as sarcomas or benign tumors. OBJECTIVES: To identify cases
      of GIST formerly diagnosed as abdominal or retroperitoneal mesenchymal tumors.
      METHODS: We reviewed the archive material on all surgical cases diagnosed as
      gastrointestinal related malignant mesenchymal tumors or GIST in our medical
      center during the last decade (1995-2004). RESULTS: Sixty-eight cases of
      retroperitoneal soft tissue sarcoma were identified. Thirty-eight were
      reconfirmed to be GIST, 19 were newly diagnosed as GIST (the hidden cases), 8
      cases were re-diagnosed as mesenchymal tumors, and 3 cases of sarcoma remained
      sarcomas. Of all the GIST tumors, c-KIT-positive and PDGFRalpha-positive tumors
      were more characteristic of primary gastric tumors, while c-KIT-positive and
      PDGFRalpha-negative tumors were found in the colorectal area. The c-KIT-negative
      and PDGFRalpha-positive cases were of gastric origin. CONCLUSIONS: Any c-KIT
      negative malignant mesenchymal mass located near the proximal gastrointestinal
      tract should also be stained for PDGFRalpha to differentiate between GIST and
      other soft tissue sarcomas. Practically, formerly diagnosed abdominal or
      retroperitoneal soft tissue sarcomas should be reviewed to identify patients with
      misdiagnosed GIST and thereby avoid future unnecessary and ineffective
      chemotherapy.

PMID- 18085041
TI  - Childhood obesity/overweight: early diagnosis to prevent premature cardiovascular
      disease.

PMID- 18085042
TI  - Kidney-ear axis.

PMID- 18085043
TI  - Pelvic splenosis mimicking an ovarian mass: a non-invasive approach.

PMID- 18085044
TI  - Mitral annulus caseous calcifications: multi-detector computed tomography
      imaging.

PMID- 18085045
TI  - Transient diabetes insipidus of pregnancy and its relationship to preeclamptic
      toxemia.

PMID- 18085046
TI  - Arteriovenous fistula and portal hypertension in a child with Down syndrome.

PMID- 18085047
TI  - Chest CT and gallium-67 SPECT scintigraphy scan co-registration in a post-heart
      transplantation patient with unresolved fever.

PMID- 18085048
TI  - Symptomatic calcified ostial lesions in both left main and right coronary
      arteries.

PMID- 18085049
TI  - Shipbreaking in the developing world: problems and prospects.
AB  - The global shipping industry relies upon the developing world to dispose of
      retired deep-sea vessels through the process of shipbreaking. In doing so the
      industry avoids the burdens of complying with developed world standards for the
      management of hazardous waste. Occupational and environmental health (OEH) risks
      associated with dismantling of beached ships, primarily in India and Bangladesh,
      are significant. Worldwide concerns about these risks, which arose in the late
      1990s, and activism by domestic organizations appear to be gathering momentum for
      global and domestic OEH reforms. This article addresses recent developments in
      characterizing these risks and in proposals to control them.

PMID- 18085050
TI  - Respiratory symptoms and pulmonary function changes among carpet weavers in Iran.
AB  - Respiratory and allergic symptoms were evaluated in 66 Iranian carpet weavers and
      66 controls with similar age and gender characteristics using a questionnaire
      including questions on work-related respiratory symptoms in the past year,
      allergies, smoking habits, and work exposure duration. A total of 28 carpet
      weavers (42%) reported work-related respiratory symptoms. Incidences of
      allrespiratory symptoms and most allergic symptoms were significantly higher in
      carpet weavers than in controls (p<0.05 - p<0.001). Moreover, most respiratory
      and allergic symptoms in carpet weavers were significantly more prominent during
      working hours (p<0.01 - p<0.001). Pulmonary function test results of the carpet
      weavers showed significant impairment compared with controls (p<0.05 - p<0.001).

PMID- 18085051
TI  - Cancer and reproductive risks in the semiconductor industry.
AB  - Although many reproductive toxicants and carcinogens are used in the manufacture
      of semiconductor chips, and worrisome findings have been reported, no broad
      epidemiologic study has been conducted to define possible risks in a
      comprehensive way. With few exceptions, the American semiconductor industry has
      not supported access for independent studies. Older technologies are exported to
      newly industrialized countries as newer technologies are installed in Japan, the
      United States, and Europe. Thus there is particular concern about the many
      workers, mostly in countries that are still industrializing, who have jobs that
      use chemicals, technologies, and equipment that are no longer in use in developed
      countries. Since most countries lack cancer registries and have inadequate
      reproductive and cancer reporting mechanisms, industry efforts to control
      exposures to carcinogens are of particular importance. Government agencies, the
      courts, industry, publishers, and academia, on occasion, collude to ignore or to
      downplay the importance of occupational diseases. Examples of how this happens in
      the semiconductor industry are presented.

PMID- 18085052
TI  - Exploratory sampling of asbestos in residences near Thetford Mines: the public
      health threat in Quebec.
AB  - In 2003-2004, the Asbestos Victims Association of Quebec undertook an exploratory
      sampling of the air and soil in the residential community of asbestos mining
      towns. In the 26 houses in the Thetford Mines area, 28 air samples were
      collected; one outdoor air sample was collected; 14 soil samples were taken; one
      dust sample was taken from a windowsill. The AHERA criterion was exceeded in 15
      of the 28 air samples collected and the World Trade Center criterion was exceeded
      in five of 26 cases. The risk of developing asbestos-related cancer following
      such in-home exposures over 30 years is estimated at 1 in 10,000. Soil from the
      driveways or backyards of nine homes was covered with residue from a tailing
      pile. Of 14 samples, seven had chrysotile content in excess of 10%; in three,
      content exceeded 60%, and one reached 100%. Dust from the windowsill had a
      chrysotile content of 1.2 million structures of all lengths/sq cm. These results
      suggest a real public health threat in the Quebec mining areas.

PMID- 18085053
TI  - Incidence and descriptive epidemiology of mesothelioma in the United States, 1999
      2002.
AB  - To estimate the recent incidence of mesothelioma in the United States and
      characterize its descriptive epidemiology, incidence data were obtained from the
      National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology
      and End Results (SEER) Program. Age-adjusted incidence rates and 95% confidence
      intervals were calculated. The U.S. incidence was 1.11 cases per 100,000 persons.
      Most cases occurred among older, white males. However, 173 cases (< 2%) occurred
      in persons younger than 40. The proportion of women with peritoneal mesothelioma
      was triple that of men (14.8% vs 5.4%). Of 40 reporting states, 11 had incidence
      rates significantly higher than the national rate.

PMID- 18085055
TI  - Commentary on effects of exposure to industry influence on ACOEM.
AB  - With the assistance of colleagues of like kidney, the authors of an article in
      this issue have drafted a damning indictment of what purports to be a learned
      society, as well as casting opprobrium on American Industry and its medical and
      scientific henchmen. In this they have not been inhibited by a legal system that
      imperils authors who dare call a knave a knave.

PMID- 18085054
TI  - American College of Occupational and Environmental Medicine (ACOEM): a
      professional association in service to industry.
AB  - The American College of Occupational and Environmental Medicine (ACOEM) is a
      professional association that represents the interests of its company-employed
      physician members. Fifty years ago the ACOEM began to assert itself in the
      legislative arena as an advocate of limited regulation and enforcement of
      occupational health and safety standards and laws, and environmental protection.
      Today the ACOEM provides a legitimizing professional association for company
      doctors, and continues to provide a vehicle to advance the agendas of their
      corporate sponsors. Company doctors in ACOEM recently blocked attempts to have
      the organization take a stand on global warming. Company doctors employed by the
      petrochemical industry even blocked the ACOEM from taking a position on
      particulate air pollution. Industry money and influence pervade every aspect of
      occupational and environmental medicine. The controlling influence of industry
      over the ACOEM physicians should cease. The conflict of interests inherent in the
      practice of occupational and environmental medicine is not resolved by the
      ineffectual efforts of the ACOEM to establish a pretentious code of conduct. The
      conflicted interests within the ACOEM have become too deeply embedded to be
      resolved by merely a self-governing code of conduct. The specialty practice of
      occupational and environmental medicine has the opportunity and obligation to
      join the public health movement. If it does, the ACOEM will have no further
      purpose as it exists, and specialists in occupational and environmental medicine
      will meet with and be represented by public health associations. This paper
      chronicles the history of occupational medicine and industry physicians as
      influenced and even controlled by corporate leaders.

PMID- 18085056
TI  - Burying the evidence: how Great Britain is prolonging the occupational cancer
      epidemic.
AB  - The U.K. authorities are failing to acknowledge or deal effectively with an
      epidemic of work-related cancers. The government's Health and Safety Executive
      (HSE) underestimates the exposed population, the risks faced as a result of those
      exposures, and the potential for prevention. The HSE fails to acknowledge the
      social inequality in occupational cancer risk, which is concentrated in manual
      workers and lower employment grades, or the greater likelihood these groups will
      experience multiple exposures to work-related carcinogens. It continues to
      neglect the largely uninvestigated and unprioritized risk to women and currently
      has neither a requirement nor a strategy for reducing the numbers and volumes of
      cancer-causing substances, processes, and environments at work. The result is
      that the U.K. faces at least 20,000 and possibly in excess of 40,000 new cases of
      work-related cancer every year, leading to thousands of deaths and an annual cost
      to the economy of between pounds 29.5bn and pounds 59bn. This paper outlines
      flaws in the HSE's approach and makes recommendations to address effectively the
      U.K.'s occupational cancer crisis.

PMID- 18085057
TI  - The economics of atrazine.
AB  - It is often claimed that atrazine is of great economic benefit to corn growers,
      but support for this claim is limited. Some cost-benefit studies have assumed
      that atrazine boosts corn yields by 6%; an extensive review found a 3%-4% average
      yield increase; other research suggests only a 1% yield effect. Syngenta, the
      producer of atrazine, also makes mesotrione, an alternative herbicide that does
      about the same amount for corn yields as atrazine. Italy and Germany both banned
      atrazine in 1991, with no decrease in corn yields or harvested area. Even if
      atrazine leads to 6% more corn production, it is not certain that this would
      justify its continued use; a 1%, or perhaps zero, change does not warrant large
      scale exposure of humans and the environment to this potentially hazardous
      chemical.

PMID- 18085058
TI  - Aspartame bioassay findings portend human cancer hazards.
AB  - The U.S. Food and Drug Administration (FDA) should reevaluate its position on
      aspartame as being safe under all conditions. Animal bioassay results predict
      human cancer risks, and a recent animal study confirms that there is a potential
      aspartame risk to humans. Aspartame is produced and packaged in China for
      domestic use and global distribution. Japan, France, and the United States are
      also major producers. No study of long-term adverse occupational health effects
      on aspartame workers have been conducted. The FDA should consider sponsoring a
      prospective epidemiologic study of aspartame workers.

PMID- 18085059
TI  - Letter to U.S. FDA commissioner. Questions about the safety of the artificial
      sweetener aspartame.

PMID- 18085060
TI  - Canada's asbestos legacy.

PMID- 18085061
TI  - Biothreat agents and pathology laboratories.
AB  - Pathologists and laboratory staff are likely to be among the first health care
      workers to be aware that a potential bioterrorism attack has occurred. To prepare
      for such an event, it is necessary to be familiar with 1) the characteristics of
      bioterrorism attacks versus natural disease outbreaks, 2) which pathogens are
      potential bioterrorism agents; 3) the types of lesions that each causes; 4) the
      microbiological characteristics of each agent; 5) the Laboratory Response Network
      and reporting requirements, and 6) what resources are available.

PMID- 18085062
TI  - Histochemical identification of methicillin-resistant Staphylococcus aureus:
      contribution to preventing nosocomial infection.
AB  - Histopathological diagnosis of bacterial infection remains a technical challenge.
      Application of histochemistry provides a prospect of the improvement of
      diagnostic quality. Methicillin-resistant Staphylococcus aureus (MRSA), the most
      common drug-resistant bacterium, is of clinical importance in making appropriate
      histopathological diagnosis. Recently, community-acquired MRSA has expanded, in
      addition to conventional hospital-acquired MRSA. Immunohistochemical
      identification of MRSA requires antibodies against both species-specific antigens
      and penicillin-binding protein 2' (PBP2'), whereas a species-specific gene and
      mec A encoding PBP2' can be the target of in situ hybridization (ISH) detection.
      Specificity verification in histochemistry should be emphasized, since S. aureus
      commonly expresses protein A in the cell wall, whose immunoglobulin-binding
      capacity is retrieved by heating pretreatment of routinely prepared sections. The
      ISH technique for MRSA needs meticulous pretreatment of routine paraffin-embedded
      sections and signal enhancement sequence. This review focuses on such
      histopathological approaches, which should have profound potential for
      contributing to decreasing and preventing nosocomial infection of MRSA.

PMID- 18085063
TI  - The pathology of dengue hemorrhagic fever.
AB  - An estimated 2.5 billion people are at risk of dengue infection, and of the 100
      million cases of dengue fever per year, up to 500,000 develop dengue hemorrhagic
      fever (DHF) or dengue shock syndrome (DSS), the life-threatening forms of the
      infection. The large majority of DHF/DSS occurs as the result of a secondary
      infection with a different serotype of the virus. While not completely
      understood, there is evidence that the target cells include dendritic reticulum
      cells, monocytes, lymphocytes, hepatocytes, and vascular endothelial cells. Viral
      replication appears to occur in dendritic cells, monocytes, and possibly
      circulating lymphoid cells, and damage to these and other target cells occurs
      through immune-mediated mechanisms related to cross-reacting antibodies and
      cytokines released by dendritic cells, monocytes, and vascular endothelium. There
      is evidence of a concomitant cellular activation as well as immune suppression
      during the infection. The activation of memory T cells results in cascades of
      inflammatory cytokines, including tumor necrosis factor-alpha, interleukins (IL
      2, IL-6, and IL-8), and other chemical mediators that increase vascular
      endothelial permeability or trigger death of target cells through apoptosis.
      Pathological studies in humans are uncommon, and a suitable animal model of
      DHF/DSS does not exist. The current treatment of DHF/DSS is symptomatic, and
      prevention is through vector control. As such, there is a great impetus for the
      development of vaccines and novel therapeutic molecules to impede viral
      replication in infected cells or counteract the effects of specific inflammatory
      mediators on target cells. The role of genetics in relation to resistance to
      DHF/DSS also requires clarification.

PMID- 18085064
TI  - Contribution of experimental paradigms of viral infectious diseases to diagnostic
      pathology.
AB  - Pathological analysis of experimental infections has been a useful method in
      virology. Host selection and route of virus inoculation are the most important
      determinants in experimental paradigms. Clinical and pathological correlations
      must be carefully determined in human and experimental infections. The cell
      tropism, cytopathic effect, and pathogenicity of viruses could be evaluated and
      defined by analysis of infected tissue. In addition, these infected tissues could
      be used as positive control for immunohistochemistry and in situ hybridization
      analysis in diagnostic pathology. This review addresses animal paradigms of
      rabies, influenza, and poliomyelitis as representatives of zoonosis and human
      specific infection with respect to animal selection for experimental infections.

PMID- 18085065
TI  - Histopathological diagnosis of infectious diseases using patients' sera.
AB  - It is expected that sera of patients suffering from infectious diseases contain
      high-titered IgG-type antibodies against the causative pathogen, particularly
      when inflammatory reactions, such as abscess or granuloma, are
      histopathologically confirmed in immunocompetent individuals. The present review
      article describes the usefulness of diluted patients' sera for identifying
      pathogens, by means of the indirect immunoperoxidase technique, in
      histopathologic specimens routinely embedded in paraffin. Infectious agents, such
      as bacteria, fungi, viruses, protozoa, and helminthes, were demonstrable with
      reliable sensitivity and limited specificity. Endogenous human immunoglobulins in
      paraffin sections were scarcely detected by the peroxidase-labeled secondary
      antibody. The method is simple, economic, useful, and beautiful for the
      histopathologic diagnosis of infectious diseases.

PMID- 18085066
TI  - HIV cases increase in New York.

PMID- 18085067
TI  - Gay students paid for prevention.

PMID- 18085068
TI  - CSI: death on site.

PMID- 18085069
TI  - Advertising and low body confidence.

PMID- 18085070
TI  - Social support for stress prevention in hospital settings.
AB  - AIMS: The purpose of this study was to identify the effects of social support,
      interacting with work stressors, on psychological stress prevention in a public
      hospital, based on Karasek's demand-control-support (DCS) model. METHODS: A self
      administered survey was conducted with 240 employees of a public hospital in the
      south-east of the United States. The survey asked for demographic information,
      details on job demands and job control as work stressors, social support, and
      depressive symptoms as the representative psychological stress symptoms. RESULTS:
      Social support was detected as a primary interpersonal positive factor buffering
      depressive symptoms. Social support was also related to job control and
      depressive symptoms in the simple correlation. Only the main effect model with
      general characteristics was significantly accepted in hierarchical regression
      analysis (p = .04). High social support was associated with low depressive
      symptom scores, which means that social support had a positive association with
      health care employees' mental well being. However, any two-way or three-way
      interaction model was not accepted. The main effect part of the demand-control
      support model was supported; however, interactions between demands, control, and
      support failed to be supported.

PMID- 18085071
TI  - Study of shift work and risk of coronary events.
AB  - BACKGROUND: The effects of shift work on coronary heart diseases (CHD) are well
      described. Most of the studies on coronary events in shift workers are supportive
      of the hypothesis that they are at increased risk. OBJECTIVE: The objective of
      this study was to investigate the relation shift work has to risk of CHD in a
      cohort of men from different Asian races working in a fertilizer plant in the
      Middle East. DESIGN: This is a case series of cohort study. SUBJECTS: The medical
      records for 2562 staff employed at the plant, from the start of the company in
      1972 till 2003, were surveyed. Of these, 648 were shift workers and 1914 were
      daytime workers. A total of 223 employees had cardiovascular event. METHODS: For
      each case we recorded the date and age at start of employment, and the age at the
      time of diagnosis. Data from their last medical examination in the company were
      used to calculate their BMI, and to register whether they were smokers, had
      diabetes, or were senior or intermediate staff. Univariate and multivariate
      statistical analyses were performed. RESULTS: The incidence of CHD is
      significantly higher in shift workers (13.5%) compared with the daytime workers
      (7.1%). Also, there was a statistically significant difference between shift
      workers and daytime workers concerning hypertension and cerebrovascular
      incidents. CONCLUSION: Our results suggest the possibility of an overall
      relationship between shift work and cardiovascular diseases.

PMID- 18085072
TI  - Lifestyles, flying and associated health problems in flight attendants.
AB  - AIMS: This study was conducted in order to investigate the effect of flying on
      Indian male and female flight attendants (FAs), flying for over 10 years and up
      to 30 years. METHODS: The FAs selected for this study were subjected to the same
      set of conditions, such as number of hours flown per month and flight routes.
      Questionnaires were prepared, based on complaints heard on a regular basis, and
      also after talking to a small sample of FAs. Nearly 100 completed questionnaires
      were returned, from 500 delivered directly to FAs by post. In addition to this,
      we met 130 FAs either before their departure or after their arrival and secured
      completed questionnaires from them, being sure to maintain anonymity. RESULTS:
      According to this study there are five major problems faced by the FAs: Stress
      (88.85%). Back pain (72.65%). Loss of memory (67.47%). Headaches (58.42%). Loss
      of hearing (51.37%). 88.85% of FAs have reported feeling stressed 'often' or
      'sometimes'. Many participants felt that if the work environment were more
      employee-friendly their stress level might come down. Back pain was reported by
      72.65% of FAs which, according to them, could be largely remedied by being
      provided with better equipment and user-friendly galleys. Loss of memory was
      prevalent in 67.47% of FAs studied. 58.42% of FAs suffer from headaches. Stress,
      loss of memory and headaches seem to share the same etiology such as hypoxia,
      jetlag and irregular sleep. Diminished hearing, prevalent in 51.37% of FAs, was
      not a major cause of worry but was largely perceived as an inconvenience.
      CONCLUSIONS: These occupational health problems of flight attendants require
      serious and immediate attention.

PMID- 18085073
TI  - Reducing resistance against polio drops.
AB  - AIMS: The present study was carried out to impart correct health education
      regarding polio eradication programme and to assess the impact of social
      mobilization of a Muslim community carried out by medical interns. METHODS: One
      round of a polio immunization campaign was selected randomly. Five highly
      resistant areas were included in the study. During house to house A-Team
      activity, teams of health workers visited the houses and resistant families were
      identified. These families refused to give polio drops to their children. On the
      second day of A-Team activity, medical interns visited those identified resistant
      families. They imparted correct health education and tried to convince them to
      give polio drops. However, after prolonged persuasion, some of the families were
      not ready to give polio drops. These more resistant families were again visited
      by more motivated and enthusiastic teams during B-Team activity, started two to
      three days after the completion of A-Team activity. Data were collected,
      tabulated and analysed. RESULTS: Total number of resistant families identified
      during house to house A-Team activity was 1025 in five high risk areas of
      Aligarh, India. Out of 1025 resistant houses, 510 (49.76%) houses were converted
      to P houses where polio drops were given to the children. Five hundred and
      fifteen (50.24%) houses remained resistant even after social mobilization by A
      Team members. These most resistant houses were again visited by B-team members.
      Out of these 515 houses, polio drops were administered in 303 (58.83%). The
      overall number of converted houses was 813 (79.32%) after A and B-team
      activities. 20.68% of families remained resistant and their children could not be
      given polio drops. CONCLUSIONS: In all high risk areas, maximum numbers of
      resistant houses were converted to P houses. These families were persuaded and
      convinced by the teams of interns, social workers and influential persons that
      polio drops did not have any side effects. They were more receptive to the advice
      given by medical interns compared to other staff members of the Government
      District Hospital because of quality of health services provided to the
      community. There is a need to impart correct health education regarding
      importance of polio drops and routine immunization more vigorously through
      information, education and communication (IEC) activities.

PMID- 18085074
TI  - Needleguard systems: an evaluation.
AB  - AIMS: The National Blood Service is responsible for ensuring that the NHS demand
      for blood products is met. The use of needles forms a fundamental procedure in
      the collection of blood. A common engineering control used to minimize
      needlestick injury is a needleguard. This study investigates the effectiveness of
      needleguards as a risk reduction measure. Injury rates, performance and the
      effectiveness of training are also addressed. METHODS: The methodology adopted
      two techniques for collecting data, namely database analysis and questionnaire
      analysis. In examining the accident database, it was identified that the
      incidence of needlestick injuries fell when needleguards were introduced in 2001.
      However, a rise in injuries was observed over the 12 months of 2003. RESULTS:
      Although the questionnaire showed that staff directly involved in the collection
      of blood believed that needleguards act to reduce the risk of injury, they also
      reported difficulties in the operation of the needleguard system. An association
      was identified between the perceived quality of training and the reported
      difficulties. It was also identified that training provided by external
      organizations had the least effect in reducing the operational difficulties.
      CONCLUSIONS: The study concludes that the use of needleguards as a successful
      control measure requires further investigation and that further research should
      be carried out to ensure the effectiveness of training in reducing injuries.

PMID- 18085075
TI  - Medicare's approach to reducing medical error... Why a stick and not a carrot?

PMID- 18085076
TI  - What military and civilian biomeds can learn from each other.

PMID- 18085077
TI  - Reporting structures: VP of finance assumes supervision of CE department.

PMID- 18085078
TI  - Getting your foot in the door.

PMID- 18085079
TI  - Asset investment recovery: a new approach to an old challenge.

PMID- 18085081
TI  - What happened? Investigating adverse events.

PMID- 18085080
TI  - Cloned hard drives reduce time, improve service.

PMID- 18085082
TI  - Cleaning the medical electronic environment: how you can contribute.

PMID- 18085083
TI  - A weighty matter: patient scales.

PMID- 18085085
TI  - LED light source: major advance in fluorescence microscopy.

PMID- 18085084
TI  - Wireless technology infrastructure: a business strategy.

PMID- 18085086
TI  - Medical device validation: how vendors can assist their customers.

PMID- 18085087
TI  - Internal audits: setting the stage for Joint Commission surveys.

PMID- 18085088
TI  - Overcoming barriers to success: collecting medical device incident data.

PMID- 18085089
TI  - Two new sterilization TIRs nearing completion.

PMID- 18085090
TI  - Offering integrated medical equipment management in an application service
      provider model.
AB  - With the advancement of medical technology and thus the complexity of the
      equipment under their care, clinical engineering departments (CEDs) must continue
      to make use of computerized tools in the management of departmental activities.
      Authors of this paper designed, installed, and implemented an application service
      provider (ASP) model at the laboratory level to offer value added management
      tools in an online format to CEDs. The project, designed to investigate how to
      help meet demands across multiple healthcare organizations and provide a means of
      access for organizations that otherwise might not be able to take advantage of
      the benefits of those tools, has been well received. Ten hospitals have requested
      the service, and five of those are ready to proceed with the implementation of
      the ASP. With the proposed centralized system architecture, the model has shown
      promise in reducing network infrastructure labor and equipment costs,
      benchmarking of equipment performance indicators, and developing avenues for
      proper and timely problem reporting. The following is a detailed description of
      the design process from conception to implementation of the five main software
      modules and supporting system architecture.

PMID- 18085091
TI  - Economic punishment.

PMID- 18085092
TI  - Who are doctors and physicians in Oklahoma?

PMID- 18085093
TI  - Non-fire carbon monoxide-related deaths, Oklahoma 1994-2003.
AB  - The purpose of this study was to determine the magnitude of non-fire carbon
      monoxide (CO)-related deaths and assess temporal trends, high-risk groups, and
      sources of CO resulting in deaths to Oklahoma residents from 1994-2003. Mortality
      data was collected from the Oklahoma Office of the Chief Medical Examiner. There
      were 281 non-fire, carbon monoxide-related deaths; 77% of CO deaths were
      suicides, 19% were unintentional, and 4% were unknown intent. The average annual
      death rate for males was nearly three times higher than females (12.0 vs. 4.7 per
      million population). Seventy-six percent of unintentional CO deaths in dwellings
      involved a furnace or heater. An audible CO detector in homes is the most
      promising technology available to prevent unintentional deaths, and there are
      several promising methods currently being researched to prevent suicides via CO
      exposure. Public and mental health authorities and health providers should
      educate the public regarding prevention of CO exposures.

PMID- 18085094
TI  - Longitudinal epiphyseal bracket.
AB  - A longitudinal epiphyseal bracket (LEB) is a defect of the tubular bones and has
      been primarily described in the hands and feet, especially the proximal
      phalanges, metacarpals, and metatarsals. The LEB results from a defective C
      shaped secondary ossification center that brackets the diaphysis and metaphysis,
      causing restricted longitudinal growth in these bones with resultant shortening
      and angular deformities. Deformities associated with metatarsal epiphyseal
      bracket include a short, broad metatarsal and medial deviation of the
      metatarsophalangeal joint (hallux varus deformity). Excision of the cartilaginous
      LEB has been proposed to prevent future soft tissue contractures and osseous
      deformities. The LEB has been associated with numerous syndromes including
      Rubinstein-Taybi syndrome, Cenani-Lenz syndactyly, isolated oligosyndactyly, and
      Nievergelt syndrome. We describe a two-month-old patient in whom plain film and
      MR imaging demonstrated bilateral bracketed first metatarsals with associated
      hallux varus deformities. Bilateral bracket excision was performed with excellent
      clinical results.

PMID- 18085095
TI  - Aspirin use in the prevention of cardiovascular events.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in the
      United States and Oklahoma, and Oklahoma ranks 50th in CVD deaths. This paper
      will describe CVD and coronary heart disease (CHD) mortality in Oklahoma and
      review current recommendations regarding aspirin use for the prevention of CHD
      events. METHODS: The CDC Compressed Mortality File for 1999-2004 was accessed.
      Average annual age-adjusted or age-specific death rates per 100,000 population
      were calculated. A literature review of data and recommendations regarding
      aspirin use was conducted. RESULTS: From 1999-2004, there were 50,170 CHD deaths
      in Oklahoma (age-adjusted rate 232.1 per 100,000). Persons 75 years and older,
      males, and blacks had the highest death rates; the death rates declined for all
      persons except those aged 35-54 years. Aspirin use has been shown to be effective
      in reducing the number of nonfatal myocardial infarction (MI) and fatal CHD,
      though studies of aspirin effects in women have found a significant reduction in
      ischemic stroke but no significant effect on fatal or nonfatal MI or CVD death.
      Aspirin use slightly increases rates of gastrointestinal bleeding and hemorrhagic
      stroke. CONCLUSION: Continued commitment to counseling patients regarding tobacco
      cessation, nutrition and exercise, and treatment to reduce blood pressure,
      cholesterol, tobacco use, and blood sugar are essential. The Oklahoma State
      Medical Association Physicians Campaign for a Healthy Oklahoma has made it a
      priority to increase awareness of the risk and benefits of aspirin use among high
      risk persons. Oklahoma physicians should assess patients at highest risk, such as
      healthy men older than 40 years, postmenopausal women (especially >or= 65 years),
      and younger people with risk factors for coronary heart disease (e.g.,
      hypertension, hyperlipidemia, diabetes, or smoking) and discuss the potential
      benefits and harms of aspirin use.

PMID- 18085096
TI  - Part XIV. Antiviral agents other than antiretrovirals: therapy for herpesvirus
      infections, viral hepatitis, and influenza.
AB  - The incidences of viral infectious diseases are increasing at an alarming rate in
      the US and worldwide. Antiviral therapy is challenging because viruses subsume
      normal host cellular mechanisms for many functions, have rapid replication rates,
      have poor error scanning when reading genetic code, and undergo frequent drug
      target mutations. This article will focus on antiviral drugs and principles of
      treatment for infections due to herpes simplex viruses (HSV1 and HSV2), varicella
      zoster virus (VZV), cytomegalovirus (CMV), hepatitis B and hepatitis C viruses,
      and influenza virus. Therapy for human immunodeficiency virus (HIV) infection
      will be discussed in the next symposium segment.

PMID- 18085097
TI  - The power of change lies within each of us...

PMID- 18085098
TI  - [Stress echocardiography in valvular heart disease].
AB  - The assessment of the severity of a valvular lesion traditionally relies on the
      evaluation of valvular anatomy and on the demonstration of resting hemodynamic
      disturbances. In patients with stenotic lesions, this is usually achieved by
      measuring the trans-stenotic pressure difference and by calculating the surface
      of the stenotic orifice. In patients with regurgitant lesions, assessment of
      lesion severity involves the demonstration of a significant volume or pressure
      overload of the various chambers participating in the process. In many instances,
      however, discrepancies are found between the severity of valvular lesions and
      either the symptoms or the hemodynamic impairment. As echocardiography is also
      the method of choice for assessing the severity of valvular disease, stress
      echocardiography may offer the unique opportunity to assess the hemodynamic
      consequences of valvular lesions both at rest and during stress.

PMID- 18085099
TI  - [Editorial comment. Stress echocardiography in valvular heart disease].

PMID- 18085100
TI  - [Molecular investigation of sudden death].
AB  - Juvenile sudden death and sudden infant death syndrome exert a deep social
      impact, due to the young age of the victims and the unexpected occurrence of
      death. Recently, genetically determined ion channel diseases have been
      demonstrated to account for many forms of juvenile sudden death sine materia and
      also for some cases of sudden infant death syndrome (Brugada syndrome, long QT
      and short QT syndromes and catecholaminergic polymorphic ventricular
      tachycardia). Moreover, a not negligible amount of juvenile sudden deaths are due
      to myocarditis as a consequence of cardiotropic viruses. Thus, it is now becoming
      mandatory to apply molecular pathology techniques also to the post mortem study
      of sudden death. In general, a long interval between death and post mortem exam
      and inadequate tissue sampling and preservation may increase the poor results of
      molecular investigation. The aim of this review was to provide evidence of the
      need to develop a molecular pathology investigation protocol to be used at post
      mortem.

PMID- 18085101
TI  - [Cardiac resynchronization therapy and reduction of mortality in heart failure: a
      proven association].
AB  - Cardiac resynchronization therapy (CRT) is currently used for treatment of
      refractory heart failure and is effective in reducing symptoms and increasing
      quality of life and exercise tolerance. Data from the literature also show that
      CRT may prolong event-free survival and reduce heart failure mortality. This
      therapy is also highly cost-effective as compared to optimized medical treatment.
      The reduction of the risk of death occurs in both nonischemic and ischemic heart
      failure, although in this latter group CRT benefit seems to be less. It is still
      controversial whether a back-up defibrillator should be implanted to all patients
      undergoing CRT. Finally, left ventricular reverse remodeling occurring after 3 to
      6 months of treatment predicts long-term benefit of CRT on mortality.

PMID- 18085102
TI  - [Usefulness of coronary angiography with multidetector computed tomography in the
      evaluation of aorto-coronary bypass patency].
AB  - BACKGROUND: Coronary angiography is actually the gold standard to visualize
      coronary artery bypass graft patency and to detect bypass stenoses. However, it
      is an invasive examination that makes use of X-ray emission and it may lead to
      deleterious effects even at low dosage. Therefore, it is still needed a non
      invasive examination with good diagnostic accuracy for the follow-up of patients
      with coronary artery bypass grafts. The aim of this study was to evaluate the
      diagnostic accuracy of a 40-row multidetector computed tomography scanner for the
      assessment of bypass surgery versus coronary angiography. METHODS: Twenty-six
      consecutive patients (20 male, 6 female, mean age 65 years) and a total number of
      68 coronary bypass grafts (25 arterial and 43 venous grafts, 111 anastomoses)
      were examined by 40-row multidetector computed tomography. RESULTS: It was
      possible to analyze coronary artery bypass graft patency for every patient. At
      coronary angiography 23 patients showed bypass stenoses or occlusion: 19 of them
      were correctly diagnosed by computed tomography (sensitivity 84%, specificity
      100%). In particular, computed tomography showed a sensitivity of 90% and a
      specificity of 100% for coronary artery bypass grafts, whereas it showed a
      sensitivity of 88% and a specificity of 94% for anastomoses. CONCLUSIONS: On the
      basis of the results of our study, computed tomography is a valuable tool for
      assessing coronary artery bypass graft patency in patients with clinical suspect
      of coronary occlusion.

PMID- 18085103
TI  - [Past, present and future of the pulmonary artery catheter].

PMID- 18085104
TI  - [Cellular immune response to 3 anesthetic techniques for simple abdominal
      hysterectomy].
AB  - BACKGROUND AND OBJECTIVE: The effect of surgery and anesthesia on the immune
      response may have a significant effect on perioperative tumor surveillance. The
      aim of this study was to characterize the cellular immune response of patients
      undergoing simple abdominal hysterectomy under 3 types of anesthesia. PATIENTS
      AND METHODS: ASA 1-2 patients undergoing simple abdominal hysterectomy were
      enrolled prospectively after they gave informed consent; the patients were
      randomized to 3 groups of 20 each to receive balanced anesthesia (group A),
      remifentanil-based anesthesia and analgesia (group B), or combined general
      epidural anesthesia (group C). Postoperative analgesia was provided in accordance
      with group assignment. Four and 24 hours after surgery, 20 mL of blood was drawn
      from each patient for analysis of leukocyte populations and lymphocyte
      subpopulations. Statistics were calculated with the SPSS software package,
      version 12.0. RESULTS: All groups had elevated neutrophil counts after surgery;
      the lowest levels were in group C (P<.05). Patients in all 3 groups developed
      lymphopenia, which was still evident 24 hours after surgery (P<.05). CD3 cell
      counts at 4 hours were lowest in patients who had received combined anesthesia
      (group C), CD19 cell counts were highest in group A, and CD16 cell counts were
      lowest in group C; this last difference was maintained at 24 hours (P<.05 for all
      these comparisons). CONCLUSION: Combined general-epidural anesthesia seems to
      lower the counts of natural killer cells that are involved in tumor surveillance
      and destruction.

PMID- 18085105
TI  - [Paresthesia in various spinal anesthesia techniques for cesarean section].
AB  - OBJECTIVE: To determine the incidence of paresthesia with different spinal
      puncture techniques using a 27-gauge Whitacre needle. MATERIAL AND METHODS:
      Spinal puncture was performed in 224 elective cesarean sections using different
      techniques in this single-blind, prospective trial. Patients were randomized to 4
      groups: group 1, combined epidural and subarachnoid puncture using an introducer
      needle; group 2, combined epidural and subarachnoid puncture without an
      introducer; group 3, subarachnoid puncture with an introducer; and group 4,
      subarachnoid puncture with an introducer to within a few millimeters of the dural
      sac, at which point the introducer was withdrawn. RESULTS: Paresthesia developed
      in 23, 11, 16 and 5 patients in groups 1, 2, 3 and 4, respectively. Various nerve
      roots were affected. In 2 and 11 cases the fourth and fifth lumbar nerve roots
      were affected; in 29 and 13 cases, the first and second sacral nerve roots were
      involved. In comparison with group 4, the risk of paresthesia was 7, 2.5 and 4
      times greater in groups 1, 2 and 3, respectively. CONCLUSIONS: Combined epidural
      subarachnoid puncture leads to a higher incidence of paresthesia in comparison
      with simple spinal puncture, probably because the lumbar puncture is performed on
      a dural sac that has been previously deformed due to the "tent effect" caused by
      the epidural needle. Fewer cases of paresthesia occur when the subarachnoid
      puncture is slow and steady and the introducer needle is withdrawn millimeters
      before it reaches the dural sac.

PMID- 18085106
TI  - [Frequency of bacterial contamination of epidural and plexus catheters in
      postoperative analgesia].
AB  - OBJECTIVE: There is little available information regarding contamination of
      perineural catheters. Incidence ranges from 5% to 57%, depending on the location
      of the catheter. The objective of this prospective study was to evaluate the
      incidence and predisposing factors of bacterial contamination of these catheters.
      PATIENTS AND METHODS: The study included 47 patients who had an epidural (24
      patients) or perineural (23 patients) catheter inserted for a minimum of 48
      hours. We recorded details of the patients' characteristics, difficulty of
      insertion and duration of placement of the catheter, antibiotic treatment
      received, and signs of local or systemic infection immediately after surgery.
      When the catheters were removed, cultures were prepared using the Maki method. A
      descriptive analysis was performed and the frequency of contamination was
      determined using various parameters. RESULTS: The incidence of contamination was
      28% (13 patients): 5/24 (21%) in epidural catheters, 6/17 (35%) in femoral
      catheters, and 2/6 (33%) in brachial and sciatic plexus catheters. Colonization
      was not influenced by the patients' characteristics, technical difficulties in
      placing the catheter, prophylactic antibiotic treatment, or the characteristics
      of the infusion administered. None of the patients presented clinical signs of
      infection. The most commonly isolated microorganism was Staphylococcus
      epidermidis, found in 10 patients (69% of the colonized catheters). CONCLUSIONS:
      Although infection of perineural catheters is exceptional when they are placed
      for 2 or more days, contamination is very common. Epidemiological studies are
      required to evaluate the variables involved.

PMID- 18085107
TI  - [Utility of monitoring with the PiCCO system during lung resection surgery].
AB  - OBJECTIVES: To evaluate the practical utility of the PiCCO system for monitoring
      cardiac output and its derived variables during lung resection surgery. PATIENTS
      AND METHODS: Patients scheduled for lung resection surgery were enrolled. After
      anesthesia had been induced, a Pulsiocath catheter was placed in the femoral
      artery ipsilateral to the thoracotomy. The following parameters were evaluated:
      ease of placement of the arterial catheter, functioning of the system, and
      appearance of complications. When the catheter was connected to the PiCCO
      monitor, cardiac output and derived variables were recorded throughout the
      procedure. RESULTS: Fifteen patients were enrolled in the study. Placement of the
      catheter in the femoral artery was easy in 9 cases (60%), difficult in 4 cases
      (27%), and impossible in 2 cases (13%). The catheter functioned correctly in 7
      patients but problems developed in 6 patients (2 cases of a poor-quality pressure
      curve, 1 case of a discrepancy of more than 20% in comparison with blood
      pressure, and 3 cases of impossibility of extracting blood samples through the
      arterial catheter because the patients were in a lateral decubitus position). No
      complications relating to arterial puncture were observed. Hemodynamic monitoring
      showed increased cardiac output after surgery. CONCLUSIONS: The results suggest
      that using the PiCCO system during lung resection surgery is of limited utility,
      given that problems developed in relation to 53% of the catheters. This makes the
      technique unreliable in the event of its being required.

PMID- 18085108
TI  - [Applications for bronchial blockers in thoracic surgery].
AB  - One-lung ventilation is commonly used to facilitate visualization of the field
      during thoracic surgery. New devices for performing this technique that have
      become available over the past 2 decades include the Univent bronchial blocker
      incorporated in a single-lumen tube, the Arndt endobronchial blocker, and the
      Cohen endobronchial blocker. Although insertion of a double-lumen tube is still
      the method used most often to isolate the lung, bronchial blockade is an
      increasingly common technique and, in certain clinical settings, provides
      advantages over the double-lumen tube. This review provides an update on new
      concepts in the use of bronchial blockers as a technique for lung isolation and
      one-lung ventilation. The literature search was performed on MEDLINE through
      PubMed using the keywords bronchial blockers and thoracic surgery. The search
      span started with 1982-the year the first modern bronchial blocker was described 
      and ended with February 2006.

PMID- 18085109
TI  - [Anesthesia in the Inca empire].
AB  - The Incas had no written language and their chroniclers say little about their
      surgery and nothing about their methods for relieving the pain it caused. It is
      possible that they did have some form of anesthesia. Available plants that had
      central effects include maize (which they used in different ways to prepare an
      alcoholic beverage called chicha), Datura, espingo, tobacco, San Pedro cactus,
      and coca. The Incas used chicha to induce unconsciousness during minor surgical
      operations and it was still being used in those regions in the 19th century to
      perform female circumcision. Datura, espingo, tobacco, and San Pedro cactus can
      produce a deep trance and, in all probability, anesthesia. There is evidence that
      they used Datura as a total or partial anesthetic. The Incas chewed coca leaves
      with lime and swallowed the resulting juice, and this allowed them to work long
      hours without eating or drinking. Modern-day Peruvian Indians say that coca only
      numbs the mouth, though it was observed in the 19th century that coca leaves
      placed in wounds provided pain relief. It is possible that the Incas used chicha 
      probably in combination with another narcotic - to achieve the total or partial
      anesthesia needed for their surgery. A decoction of coca leaves may have been
      used as a topical anesthetic.

PMID- 18085110
TI  - [Emergency cesarean in a patient with Coffin-Siris syndrome].
AB  - Coffin-Siris syndrome is a rare genetic disease characterized by coarse facial
      features, sparse scalp hair, hirsutism, hypoplasia of the distal phalanges,
      hypoplastic nail in the fifth digit, and mental retardation and delayed growth
      evident in both weight and height. Most cases are sporadic, but the possibility
      of recessive or dominant autosomal inheritance has been suggested. Facial
      abnormalities that make intubation difficult and mental retardation that
      interferes with cooperation are aspects of this disease that can affect the
      choice of type of anesthesia. We report the case of a parturient with Coffin
      Siris syndrome who refused epidural analgesia for labor pain and for whom the
      obstetrician later decided that an emergency cesarean was necessary due to fetal
      distress.

PMID- 18085111
TI  - [Anesthesia in a patient with Angelman syndrome].
AB  - We describe the perioperative treatment of a patient diagnosed with Angelman
      syndrome, which is usually caused by a deletion in chromosome 15. The patient
      showed the characteristic signs of psychomotor retardation, epilepsy, lack of
      speech, frequent laughter and happy demeanor, light skin, blue eyes, and blond
      hair, hyperactivity, and sleep disturbance. He was scheduled for multiple tooth
      extractions under general anesthesia. Intravenous anesthesia was induced using
      ketamine, propofol, and rocuronium, and was maintained with low concentrations of
      sevoflurane. There were no incidents during or after surgery. The chromosomal
      abnormality that causes Angelman syndrome is located on the same genes that
      control the production of gamma-aminobutyric acid-A receptors, which are
      activated by most intravenous and inhaled anesthetic agents. The effect of the
      condition on the response of these agents is unknown. The combined use of
      propofol, ketamine, and sevoflurane at low doses provided adequate anesthesia for
      this patient. Other characteristics of the syndrome that may affect the use of
      anesthesia in these patients are discussed.

PMID- 18085112
TI  - [Neurilemoma of the brachial plexus: clinical characteristics and anesthetic
      management during resection].

PMID- 18085113
TI  - [The personal digital assistant in anesthesiology].

PMID- 18085115
TI  - [The acute pain unit and the treatment of postoperative pain in Andalusia: truth
      or fiction?].

PMID- 18085114
TI  - [Acute closed-angle glaucoma after gynecological surgery under general
      anesthesia].

PMID- 18085116
TI  - [Carotid artery infusion of propofol for the Wada test].

PMID- 18085117
TI  - [GlideScope video laryngoscope intubation of a patient with ankylosing
      spondylitis].

PMID- 18085118
TI  - [Transient tetraplegia after excision of a giant cervical osteophyte extending
      from C5 to C6].

PMID- 18085119
TI  - Data Safety Monitoring Boards.

PMID- 18085120
TI  - Varied distribution of RhD epitopes in the Indian population.
AB  - BACKGROUND: Inhabited by more than 4000 caste and tribal groups, India has an
      extremely heterogenous population. For thousands of years many tribal groups have
      practised endogamy and are practically genetically isolated. Traditionally,
      polyclonal anti-D reagent has been used for RhD typing; though monoclonal
      antibodies are increasingly being used. As a result, blood banks find it
      difficult to assign the RhD status to an increasing number of people. As
      monoclonal anti-D typing reagents may not detect all RhD antigen epitopes, we
      studied the RhD antigen epitope heterogeneity in different population groups in
      India. METHODS: Red cells of 5315 RhD-positive individuals belonging to different
      castes and tribes of India were tested with 30 different epitope-specific
      monoclonal anti-D antibodies. RESULTS: No single monoclonal antibody could detect
      all RhD-positive red cells detected by polyclonal antisera. The highest
      proportion of D antigen was detected by LHM 76/55 and BRAD-8 (98%) monoclonal
      antibodies. CONCLUSION: We need to determine the correct mix of monoclonal
      antibodies that will detect nearly all RhD antigens detected by polyclonal anti-D
      sera. Similarly, before accepting monoclonal anti-D for therapeutic use, it would
      be necessary to determine the appropriate ones for use in the Indian population.

PMID- 18085121
TI  - Megaloblastic anaemia: prevalence and causative factors.
AB  - BACKGROUND: Megaloblastic anaemia is not uncommon in India, but data are
      insufficient regarding its prevalence, and causative and precipitating factors.
      We did a prospective study to document such data for patients of megaloblastic
      anaemia. METHODS: All patients presenting to our hospital over a period of 6
      months with a haemoglobin < 10 g/dl and/or mean corpuscular volume > 95 fL and
      blood film findings consistent with megaloblastosis were included in the study.
      Demographic data, diet, drug intake, previous blood transfusion and presenting
      symptoms were recorded. Clinical findings were obtained from medical records of
      patients. Complete blood counts, blood film examination, reticulocyte count and
      cobalamin and folate assays were done. Results of liver function tests and bone
      marrow slides were available for review. RESULTS: Megaloblastic anaemia was
      diagnosed in 175 patients with anaemia. Assays were done on 120 patients (55 were
      lost to follow up) and results showed cobalamin deficiency in 78 patients (65%),
      combined cobalamin and folate deficiency in 20 patients (12%) and pure folate
      deficiency in 8 patients (6%). Fifteen per cent of patients had normal or high
      values of both vitamins, having received blood or haematinics before the
      diagnosis was established. The peak incidence of megaloblastic anaemia was in the
      age group of 10-30 years (48%), with female preponderance (71%). The predominant
      symptoms were fatigue, anorexia and gastritis, low grade fever, shortness of
      breath, palpitations and mild jaundice. Twenty-five per cent of patients were on
      acid-suppressing medication and 15% had previous transfusion for anaemia. Eighty
      seven per cent of patients with cobalamin deficiency and 75% with folate
      deficiency were lactovegetarians. In the combined deficiency cohort, 71% were
      vegetarians and 29% were occasional non-vegetarians. Physical findings were
      pallor (85%), glossitis (29%), mild icterus (25%) and hyperpigmentation (18%).
      Abnormal haematological findings were mean corpuscular volume 77-123 fL (9
      patients had iron deficiency), red cell distribution width 16%-44%, pancytopenia
      in 62% of patients, reticulocyte count > 2% in 42% of patients and typical
      megaloblastic blood films in all patients. Bone marrow smears available in 22
      patients showed moderate-to-severe megaloblastosis. Thirty-two per cent of
      patients in whom liver function tests were done showed indirect bilirubinaemia
      with normal enzymes. CONCLUSION: Megaloblastic anaemia was diagnosed from
      complete blood counts, red cell indices, blood film examination and assays of the
      two vitamins. Bone marrow examination was not essential for diagnosis. Cobalamin
      deficiency was the major cause of megaloblastosis. Aetiological factors were a
      diet poor in cobalamin or folate, increased requirements during the growth period
      and pregnancy, and the use of acid-suppressing medication. Physicians managing
      these patients need to be aware of the timing of blood sampling for assays, that
      haematinics and transfusions provide only short term benefits, and that long term
      follow up and diet counselling is crucial.

PMID- 18085122
TI  - Perceptions about suicide: a qualitative study from southern India.
AB  - BACKGROUND: Studies from India have reported high rates of suicide. We aimed to
      understand the social and cultural factors that modulate the risks related to
      suicide. METHODS: Focus group discussions were conducted with community health
      workers (1 group) and members of the public (6 groups). In-depth interviews were
      also conducted with 5 people who had attempted suicide and survived. The
      interviews were tape-recorded and transcribed verbatim. The results were
      summarized and analysed using standard procedures. RESULTS: The most common
      causes for suicide were interpersonal and family problems, and financial
      difficulties. Mental illness was also reported as causal. All 5 subjects who had
      attempted suicide mentioned marital and family discord as the cause. The majority
      of the general population and all the subjects who had attempted suicide were not
      aware of any community and support services for the prevention of suicide.
      CONCLUSION: Our study reveals that people perceived suicide as an option to
      overcome interpersonal, family and financial stress among normal individuals as
      well as those with mental illness. Healthcare providers should place greater
      emphasis on educating the general public regarding the policies and services
      available for suicide prevention.

PMID- 18085123
TI  - Dependence syndrome and intoxication delirium associated with zolpidem.
AB  - The use of zolpidem by general practitioners and specialists alike has increased.
      Earlier, it was considered safe by physicians, i.e. devoid of dependence
      potential and the risk of serious adverse events. We report 5 patients seen over
      a 36-month period at the Post Graduate Institute of Medical Education and
      Research, which highlight the need for caution in the use of this drug.

PMID- 18085124
TI  - Pesticide poisoning.
AB  - Acute poisoning with pesticides is a global public health problem and accounts
      for as many as 300,000 deaths worldwide every year. The majority of deaths occur
      due to exposure to organophosphates, organochlorines and aluminium phosphide.
      Organophosphate compounds inhibit acetylcholinesterase resulting in acute
      toxicity. Intermediate syndrome can develop in a number of patients and may lead
      to respiratory paralysis and death. Management consists of proper oxygenation,
      atropine in escalating doses and pralidoxime in high doses. It is Important to
      decontaminate the skin while taking precautions to avoid secondary contamination
      of health personnel. Organochlorine pesticides are toxic to the central nervous
      system and sensitize the myocardium to catecholamines. Treatment involves
      supportive care and avoiding exogenous sympathomimetic agents. Ingestion of
      paraquat causes severe inflammation of the throat, corrosive injury to the
      gastrointestinal tract, renal tubular necrosis, hepatic necrosis and pulmonary
      fibrosis. Administration of oxygen should be avoided as it produces more
      fibrosis. Use of immunosuppressive agents have improved outcome in patients with
      paraquat poisoning. Rodenticides include thallium, superwarfarins, barium
      carbonate and phosphides (aluminium and zinc phosphide). Alopecia is an atypical
      feature of thallium toxicity. Most exposures to superwarfarins are harmless but
      prolonged bleeding may occur. Barium carbonate Ingestion can cause severe
      hypokalaemia and respiratory muscle paralysis. Aluminium phosphide is a highly
      toxic agent with mortality ranging from 37% to 100%. It inhibits mitochondrial
      cytochrome c oxidase and leads to pulmonary and cardiac toxicity. Treatment is
      supportive with some studies suggesting a beneficial effect of magnesium
      sulphate. Pyrethroids and insect repellants (e.g. diethyltoluamide) are
      relatively harmless but can cause toxic effects to pulmonary and central nervous
      systems. Ethylene dibromide-a highly toxic, fumigant pesticide-produces oral
      ulcerations, followed by liver and renal toxicity, and is almost uniformly fatal.
      Physicians working in remote and rural areas need to be educated about early
      diagnosis and proper management using supportive care and antidotes, wherever
      available.

PMID- 18085125
TI  - Management of type 2 diabetes mellitus with oral antihyperglycaemic therapy.

PMID- 18085126
TI  - The glycerol tragedy revisited.

PMID- 18085127
TI  - Liver transplantation in India.

PMID- 18085128
TI  - Acute shortage of medical teachers: what's the solution?

PMID- 18085129
TI  - How does clinical diagnosis of mycobacterial adenitis correlate with histological
      findings?
AB  - OBJECTIVE: To describe and compare histopathological findings with clinical
      criteria in diagnosis of TB adenitis. METHODS: Lymph node biopsies were obtained
      from 213 patients. Specimens were processed for culture and histopathologic
      examination, using standard methods. One hundred blocks with good preservation of
      tissue morphology were selected for detailed histological examination. RESULTS:
      About 75% of 213 patients had granulomas. In the remaining 25%, neither
      histopathological nor microbiological evidence of mycobacterial disease was
      found. Of 100 blocks selected for detailed examination, 79 blocks had
      granulomatous changes. The granulomas were well organised in 24%, mixed in 33%,
      and poorly organised in 43%. Langhans giant cells and acid-fast bacilli were
      observed in 88.6% and 21.5% of the 79 blocks, respectively. Cultured specimens
      were positive in about 10% of 79 biopsy specimens. CONCLUSIONS: Histological
      evidence of mycobacterial disease was only found in three quarters of patients
      that were clinically diagnosed and started on empirical treatment for tuberculous
      adenitis. Neither histological nor mycobacteriological evidence was found in a
      quarter of the patients who were already on treatment for TB, basing on clinical
      criteria. These findings call for new research on simple diagnostic tools for
      patients who seek care for s ymptoms of extra-pulmonary TB.

PMID- 18085130
TI  - Age at menarche, menstrual patterns, sexual health knowledge, attitudes and
      premarital sexual partners of female athletes in Ibadan, Nigeria.
AB  - OBJECTIVE: The study aimed to find out age at menarche, menstrual patterns,
      attitudes and premarital sexual partners of female athletes in Ibadan Nigeria.
      METHOD: The study adopted descriptive cross sectional survey design involving 250
      female athletes training or camping under Oyo State Sports Council, Ibadan,
      Nigeria. The data collection tool was a self-developed validated questionnaire.
      Data was analyzed using SPSS package. RESULTS: Majority (44.0%) had menarche
      between 12-13 years, (71.6%) had regular menstrual period, more than 50% of the
      study participants had correct knowledge of all sexual health knowledge items,
      more than 50% of the responses to items on attitude suggested they were not
      favourably disposed to premarital sex. However, 72.4% had premarital sex with the
      person they wanted to marry, 44.0% with male athletes, 28.0% with coaches and
      23.1% with other staff of the sports council. CONCLUSION: Majority of the study
      participants had sexual health knowledge but sizeable proportion of the study
      participants also had attitudes that favour premarital sex and had different
      types of sexual partners. There is therefore an urgent need for health education
      of the female athletes especially against sexually transmitted infections
      including HIV/AIDS and education of coaches and sports officials of the need to
      serve as role models in the area of sexuality to athletes.

PMID- 18085131
TI  - Childhood asymptomatic malaria and nutritional status among Port Harcourt
      children.
AB  - OBJECTIVE: Our study in Port Harcourt children with asymptomatic malaria aimed at
      assessing the baseline anthropometric indices of nutritional status, and whether
      their nutritional status (especially under nutrition) offers any advantage for
      living in malaria endemic areas. DESIGN: Cross-sectional study was used. SETTING:
      Rumueme Community in Port Harcourt, Nigeria. SUBJECTS: Apparently healthy
      children aged 1-8 years of both sexes (Boys = 117, Girls = 123; Ratio 1:1.05),
      240 children from randomly selected households within the study community
      participated in the study. RESULTS: Of the 240 children, 66 (27.5%) were infected
      with malaria (P falciparum). Children below 5 years had a higher parasitaemic
      rate (36.36%) than those in 5-8 years group (21.27%). Our baseline data showed
      that 17.5% were underweight (WFA Z < -2), 3.75% were stunted (HFA Z < -2) and
      22.5% were wasting (WFH Z < -2). Children who are underweight were found to be at
      higher risk of acquiring malaria infection than the well nourished children (RR =
      1.02, chi2 = 0.320, p < 0.02, 95% CI 0.34-2.37). Under nutrition was more
      prominent in the children below 5 years than the older children (RR = 3.625, chi2
      = 10.36, p < 0.006, 95% CI 1.81-5.43). The haemoglobin value of parasitized
      children (10.8 +/- 1.9 g/dl) was significantly lower than the non-parasitized
      group (11.3 +/- 1.7 g/dl,) (p < 0.01). CONCLUSION: We concluded that the presence
      of under nutrition places children (especially below 5 years of age) at higher
      risk of malaria related morbidity. Children in malaria endemic areas need
      adequate nutrition to withstand the negative impact of malaria.

PMID- 18085132
TI  - Consumer survey of malaria fact card: an educational and communication tool in
      Tanzania.
AB  - OBJECTIVE: To determine the usefulness of the malaria fact card as a health
      educational and communication tool in Dar Es Salaam. METHODS: A prospective
      consumer survey pilot study on the malaria fact card, a health educational and
      communication tool was carried out between January and February 2004 in Dar Es
      Salaam, Tanzania. Parameters studied include consumers' understanding of the
      malaria fact card, consumer behavioural responses and awareness of malaria
      prevention and treatment. A total of 131 respondents from 10 randomly selected
      community pharmacies in which malaria fact cards were distributed since 2003
      participated in the study. Data were collected using structured and semi
      structured questionnaires. RESULTS: It was found that 95% of respondents reported
      that the fact card was easy to read and understand. The study revealed that 64.6%
      (n = 127) responses acknowledged getting new information on correct treatment of
      malaria using Sulphadoxine-Pyrimethamine (SP), while 8.6% acquired new
      information about prevention strategies. Only 33% of the consumers surveyed
      indicated to visit the pharmacies on regular basis. Further, results indicated
      that 84% of respondents asked the pharmacists for health information and/or
      advice when purchasing antimalarial medicines. Of all responses 38% (n = 179)
      related to prevention strategies and 26.8% related to correct use of SP
      medications. CONCLUSION: We conclude that the malaria fact card is useful as a
      health educational and communication tool . It is recommended that pharmacists
      should provide quality and educative information through use of communication
      tools such as updated malaria fact cards.

PMID- 18085133
TI  - Prevalence of and factors associated with alcohol consumption in Temeke in
      August/September, 2002.
AB  - OBJECTIVE: To determine the prevalence of alcohol consumption in Temeke district
      by social demographic characteristics. METHODOLOGY: Population-based cross
      sectional study was conducted in Temeke district involving persons above 15 years
      of age. We selected Keko ward for the study and simple random sampling procedure
      was used to select clusters of ten-cell leaders. All households in the selected
      ten-cell leaders were included in the study sample. The study was cleared by the
      Ethical Clearance Committee of the Muhimbili University of Health and Allied
      Sciences, Dar es Salaam. Chi-squared (chi2) test for contingency tables was used
      to assess statistical significance and the results were considered significant if
      p-value was less than 0.5. RESULTS: A total of 246 persons participated in the
      survey and of these 22% (54) were alcohol drinkers. The age group 25-35 years
      showed a high prevalence with a male preponderance. There was no difference in
      the drinking pattern between single and married subjects with 20.1% and 22%
      respectively. On education basis, 22.1% of primary school leavers drank alcohol.
      Teachers and businessmen drank alcohol more than other occupational groups with
      33.3% and 25.6% respectively. Bad health effect was the most perceived alcohol
      related problem occurring in 65.4% of all the respondents. CONCLUSION: It was
      concluded that alcohol consumption was low in Temeke as compared to other regions
      and was seen more in males than females and bad health effect was the most
      perceived problem resulting from alcohol consumption. We recommend that similar
      studies should be done in other districts of Dar-es-Salaam to validate our
      findings.

PMID- 18085134
TI  - Safe-delivery practices in rural Bangladesh and its associated factors: evidence
      from Bangladesh demographic and health survey-2004.
AB  - OBJECTIVES: This study examined the safe-delivery practices and its associated
      factors among rural Bangladeshi women. DESIGN: Cross-sectional survey data from
      Bangladesh Demographic and Health Survey (BDHS) 2004 were used. SETTING: Rural
      Bangladesh. PARTICIPANTS: A total of 3874 ever-married rural women age 10-49
      years. MEASUREMENTS: Age, education, working, religion, clinic visit, association
      with media, place and types of attendants at delivery. RESULTS: About 94%
      deliveries took place at homes and 67% were assisted by the untrained traditional
      birth attendants called Dai. The qualified doctors and nurses (professionals)
      assisted only 9% of the deliveries while about 13% are by the trained traditional
      birth attendants. Age group has a significant effect on safe-delivery practices.
      Education of the respondents as well as their partner's has direct effect on
      delivery practices. The uneducated women were less likely to have their delivery
      assisted by the medically trained persons (MTPs) while women with 10 or more
      years of schooling had 29 times higher probability than the uneducated women.
      Currently working and religion had also statistically significant. Mass media
      influences directly delivery practices in rural areas. The women who listen to
      radio and watch television had more than 2 times higher probability of having
      delivery assisted by MTPs than that of non-user counterparts. There is more than
      4 times higher chance of delivery assisted by the MTPs than that of women with no
      reading of news papers or magazines. CONCLUSIONS: Delivery practices in rural
      Bangladesh are unsafe, took place at homes, conducted by untrained traditional
      birth attendants and associated positively with demographic, socio-economic,
      cultural and programmatic factors.

PMID- 18085135
TI  - Taeniasis and its socio-economic implication in Awassa town and its surroundings,
      Southern Ethiopia.
AB  - OBJECTIVE: The study was conducted between October 2005 and April 2006 in Awassa
      town and its surroundings to investigate the status of T. saginata taeniasis, its
      socio-economic importance and potential risk factors. METHODS: Questionnaire
      survey was conducted on 120 volunteer individuals selected at random.
      Additionally, retrospective study on taenicidal drugs inventories at 12
      pharmaceutical shops was conducted. RESULTS: T. saginata taeniasis was a wide
      spread problem in the town and its surroundings with overall prevalence of 64.2%
      (77 out of 120) and maximum infection frequencies of five times per year. The
      prevalence of taeniasis was significantly varied between religion, occupation,
      raw meat consumption and use of spices with raw meat. Accordingly, Christian
      communities (OR = 5.2, 95% CI = 1.20-22.50), high-risk groups (OR = 4.05, 95% CI
      = 1.27-12.93), raw meat consumers (OR = 7.9, 95% CI = 2.46-5.66), and spices
      users (OR = 11.6, 95% CI = 2.85-47.28) had higher likelihood of acquiring
      taeniasis than Muslim communities, low risk groups, cooked meat eaters and non
      spices users, respectively. Conversely, prevalence was not varied between sex,
      age, marital status and educational backgrounds of the respondents. Respondents'
      preferences to available taenicidal drugs had strong linear relationship with
      drug dose sold (R2 = 0.92), and showed that Niclosamide (46.8%) was the drug of
      first choice while Praziquantel (13%) was the least preferred drug. The
      taenicidal drug doses and treatment cost from 2002 to 2005 were estimated to be
      4,913,346 adult doses and 820,343 USD (7,219,021 Eth. Birr as per rate of 2006).
      CONCLUSION: Taeniasis was a wide spread problem with higher prevalence and
      frequent infections in the town and its surroundings. Sociocultural conditions
      and occupation were the major risk factors for the occurrence of the disease.
      Hence, owing to its public health and economic importance, taeniasis deserves
      serious attention in order to safeguard the public health.

PMID- 18085136
TI  - Appraisal on the prevalence of malaria and anaemia in pregnancy and factors
      influencing uptake of intermittent preventive therapy with sulfadoxine
      pyrimethamine in Kibaha district, Tanzania.
AB  - OBJECTIVE: To appraise the prevalence of malaria and anaemia in antenatal
      mothers; and explore the factors influencing coverage of intermittent preventive
      treatment (IPT) with sulfadoxine-pyrimethamine (SP) under operational conditions
      in the national programme for malaria control in pregnancy. DESIGN: Descriptive
      cross-sectional survey. SETTING: The reproductive and child health clinic in
      Kibaha district hospital, Tanzania SUBECTS: Pregnant mothers on routine antenatal
      visits MAIN OUTCOME MEASURES: Prevalence of malaria (peripheral parasitaemia) and
      anaemia, coverage of IPT with SP and the factors influencing coverage. RESULTS: A
      total of 395 mothers were recruited; 27.3% had malaria. Moderate anaemia i.e.
      haemoglobin (Hb) level 8. -10.9 g/dl was detected in 56.7% of mothers; 34.2% had
      severe anaemia (Hb < 8.0 g/dl). Hb > 8.0 g/dl was strongly associated with
      negative parasitaemia while Hb < 8.0 gidl was strongly associated with positive
      parasitaemia. About a third (40.0%) of the mothers did not receive SP for IPT

PMID- 18085138
TI  - [Randomized controlled study on AMIE methods for treatment of movement disorder
      in the child of convulsive cerebral palsy].
AB  - OBJECTIVE: To observe the curative effect of AMIE methods on movement disorder in
      the child of convulsive cerebral palsy (CP). METHODS: One hundred and twenty
      cases of CP children were randomly divided into an integration treatment group
      and a rehabilitation group, 60 cases in each group. The integration treatment
      group were treated with acupuncture (A), massage (M), injection (I) and five
      animal exercise (E) therapies for 60 times, and the rehabilitation group were
      treated with Bobath training therapy for 60 times. Scores for movement function
      before and after treatment were used for assessment of therapeutic effect. Twelve
      months later, understand whether or not the children can walk on ones own.
      RESULTS: The total effective rate was 76.70% in the integration treatment group
      and 58.4% in the rehabilitation group, with no significant difference between the
      two groups (P > 0.05); there were significant differences in the two groups in
      differences of movement function scores before and after treatment (P < 0.05).
      After one year's follow-up survey, 36 children could walk by themselves in the
      integration treatment group, which were significantly more than 24 children in
      the rehabilitation group (P < 0.05). CONCLUSION: AMIE methods is effective for
      treatment of movement disorder in the child of convulsive cerebral palsy, and the
      short-term therapeutic effect is same as that of Bobath training method and the
      long-term therapeutic effect is better than that of Bobath training method.

PMID- 18085137
TI  - [Multi-central clinical valuation of SHAO's "five needling methods" for treatment
      of asthma of deficiency of lung and spleen].
AB  - OBJECTIVE: To make multi-central clinical valuation of SHAO's "five needling
      methods" for treatment of asthma of deficiency of lung and spleen. METHODS: Two
      hundred and ten cases were randomly divided into a test group and a control
      group, 105 cases in each group. The test group were treated with SHAO's "five
      needling methods", with Feishu (BL 13), Dazhui (GV 14), Fengmen (BL 12) selected;
      the control group were treated with routine needling method, with Dingchuan (EX-B
      1), Gaohuang (BL 43), Feishu (BL 13), Taiyuan (LU 9), Pishu (BL 20), etc.
      selected. The treatment in the two groups was given once each day, for 4 weeks,
      with one-day interval each 6-consecutive day. RESULTS: Fourteen cases were
      clinically cured, 42 cases were markedly effective, 32 cases were effective and 6
      cases were ineffective in the test group with an effective rate of 93.6%; and 8,
      30, 41 and 13 cases in the control group, respectively, with an effective rate of
      85.9%, with a significant difference between the two groups (P < 0.05). After
      treatment, the symptoms and signs, pulmonary function in the test group were
      better than those in the control group (P < 0.05). CONCLUSION: SHAO's "five
      needling methods" has significant therapeutic effect for treatment of asthma of
      deficiency of lung and spleen, which is better than that of the routine needling
      method.

PMID- 18085139
TI  - [Effect of acupuncture at Sifeng (EX-UE 10) on serum leptin in the child of
      anorexia].
AB  - OBJECTIVE: To observe effect of acupuncture at Sifeng (EX-UE 10) on serum leptin
      level in the child of anorexia, so as to reveal relation between changes of blood
      leptin level and anorexia of child. METHODS: Forty-two cases were randomly
      divided into 3 groups. The treatment group A (n = 15) were treated with
      acupuncture at Sifeng (EX-UE 10), once each week, 3 consecutive sessions
      constituting one course; the treatment group B (n = 15) were treated with
      acupuncture at Sifeng (EX-UE 10), once two weeks, 3 consecutive sessions
      constituting one course; the medication group (n = 12) were treated with oral
      administration of Lactein tablets, 1 - 2 tablets each time, 3 times each day, 4
      weeks constituting one course. RESULTS: The effective rate was 93.3% in the
      treatment group A and 93.3% in the treatment group B, which were higher than that
      in the medication group, with a very significant differences (P < 0.01); after
      treatment, the serum leptin levels in the 3 groups had very significant changes
      (P < 0.01); the improvement of serum leptin levels in the treatment group A and B
      were better than that in the medication group (P < 0.05). CONCLUSION: Acupuncture
      at Sifeng (EX-UE 10) can promote secretion of serum leptin in the child of
      anorexia, and improve anorexia.

PMID- 18085140
TI  - [Clinical observation on distinctive water-medicine cup therapy for treatment of
      cervical spondylopathy of cervical type].
AB  - OBJECTIVE: To use distinctive water-medicine cup therapy for treatment of
      cervical spondylopathy of cervical type as a sample to provide a more effective
      cupping method for clinic. METHODS: One hundred and forty cases were randomly
      divided into a medicine cup group (n = 47), a water cup group (n = 47) and a
      empty cup group (n = 46). The medicine cup group were treated by cupping therapy
      with a self-made medicine cup with 45 degrees C Chinese herb solution; the water
      cup group were treated with a cup with 45 degrees C water, and the empty cup
      group with a cup with nothing. Clinical symptoms and signs were observed for
      comparison of therapeutic effects. RESULTS: Clinically cured was 39 cases, and
      markedly effective was 8 cases in the medicine cup group; 20 cases were
      clinically cured, 22 cases were markedly effective and 5 cases were effective in
      the water cup group; 12 cases were clinically cured, 19 cases were markedly
      effective and 15 cases were effective in the empty cup group. There were
      significant differences in the ratio of cases of different therapeutic effects
      and the difference of pain score before and after treatment between the medicine
      cup group and the water cup group (P < 0.05), between the water cup group and the
      empty cup group (P < 0.05), and between the medicine cup group and the empty cup
      group (P < 0.01). CONCLUSION: The therapeutic effect of the distinctive medicine
      cup is better than the water cup group, and the water cup group is better than
      the empty cup group.

PMID- 18085141
TI  - [Treatment of residual neuralgia of herpes zoster by ear point taping and
      pressing therapy combined with acupoint-injection].
AB  - OBJECTIVE: To Assess therapeutic effect of ear point taping and pressing therapy
      combined with acupoint-injection on residual neuralgia of herpes zoster. METHODS:
      One hundred and sixteen cases were randomly divided into a comprehensive group (n
      = 60) and a medication group (n = 56). The medication group were treated with
      routine western medicine, and the comprehensive group with ear point taping and
      pressing therapy combined with acupoint-injection besides the routine western
      medicine. Auricular points selected for ear point taping and pressing were
      Shemen, Neifenmi (endorine), Pizhixia (subcortex), Gan (liver), Dan
      (gallbladder), Fei (lung) and corresponding auricular points to the lesion parts,
      with the two ears alternatively used, pressing each day; points selected for
      point-injection of VitB12 were Zusanli (ST 36), Neiguan (PC 6), Quchi (LI 11),
      Taichong (LR 3). The pain degrees, the time of pain alleviation and pain ceasing
      of the patient were regularly recorded. RESULTS: The average time of pain
      alleviation and pain ceasing of the patient in the comprehensive group were
      significantly shorter than those in the medication group (P < 0.01). The cured
      rate and the cured and markedly effective rate were 60.0% and 83.3% in the
      comprehensive group, and 28.6% and 50.0% in the medication group, with
      significant difference between the two groups (P < 0.05). CONCLUSION: Ear point
      taping and pressing therapy combined with acupoint-injection is effective and
      safe for treatment of residual neuralgia of herpes zoster.

PMID- 18085142
TI  - [Clinical observation on Yuanluo Tongjing needling method for treatment of mild
      cognitive impairment].
AB  - OBJECTIVE: To observe therapeutic effect of Yuanluo Tongjing needling method for
      treatment of mild cognitive impairment and search for an effective therapy of TCM
      for mild cognitive impairment. METHODS: Sixty cases were randomly divided into an
      observation group and a control group, 30 cases in each group. The observation
      group were treated by Yuanluo Tongjing needling method with Baihui (GV 20),
      Danzhong (CV 17), Guanyuan (CV 4), Shenmen (HT 7), etc. selected, and the control
      group by oral administration of Aricept, 2.5 mg. Changes of scores of all indexes
      in clinical memory scale and memory quotient (MQ) before and after treatment were
      investigated in the two groups, and clinical therapeutic effects were assessed by
      using MQ increasing values. RESULTS: After treatment for 30 days, the scores of
      memory quotient, direction memory, picture free memory, re-cognition of no
      significant picture forms and associated memory of human picture characteristics
      significantly increased (P < 0.01, P < 0.05) in the observation group; and all
      the indexes except associated memory in the control group significantly changed
      (P < 0.05), with no significant difference between the two groups (P > 0.05). The
      good rate for memory effect was 80.0% in the observation group and 76.7% in the
      control group with no significant difference between the two groups (P > 0.05).
      CONCLUSION: Yuanluo Tongjing needling method can improve memory ability of the
      patient of mild cognitive impairment.

PMID- 18085143
TI  - [Observation on therapeutic effect of acupuncture at point "Xiajiquan" on
      muscular strength of finger after apoplexy].
AB  - OBJECTIVE: To approach to the best therapy for recovery of fingers function after
      apoplexy. METHODS; One hundred and twenty-three cases were randomly divided into
      an observation group of 63 cases and a control group of 60 cases. The control
      group were treated by acupuncture at Quchi (LI 11), Shousanli ( LI 10), Waiguan
      (TE 5), etc., and the observation group by acupuncture at point "Xiajiquan"
      besides the acupoints for the control group. After treatment of 10 sessions, the
      therapeutic effects were assessed. RESULTS: The cured and markedly effective rate
      was 74.6% in the observation group and 40.0% in the control group, the
      observation group being significantly better than the control group (P < 0.05).
      CONCLUSION: Point "Xiajiquan" has a better therapeutic effect on derivation of
      finger muscular strength.

PMID- 18085144
TI  - [Observation on ear point taping and pressing therapy for treatment of primary
      dysmenorrhea].
AB  - OBJECTIVE: To observe therapeutic effect and prognosis of ear point taping and
      pressing therapy for primary dysmenorrhea. METHODS: One hundred and fourteen
      cases were randomly divided into an ear taping and pressing group of 60 cases and
      a western medication group of 54 cases. The ear taping and pressing group were
      treated by ear point taping and pressing at Shenmen, Zigong (uterus), Neifenmi
      (endorine), Pizhixia (subcortex), Jiaogan (sympathesis) and Shen (kidney), which
      were taped and pressed by a adhesive plaster with Vaccaria seeds. The western
      medication group were treated with oral administration of Indomeixin enteric
      tablets. The therapeutic effects were assessed after treatment of 3 menstrual
      cycles. RESULTS: The total effective rate was 91.7% in the ear taping and
      pressing group and 77.8% in the western medication group with a significant
      difference between the two group (P < 0.05); and the long-term therapeutic effect
      in the ear taping and pressing group was better than that in the western
      medication group. CONCLUSION: Ear point taping and pressing therapy has
      significant therapeutic effect on primary dysmenorrhea.

PMID- 18085145
TI  - [Observation on therapeutic effect of point pressure combined with massage on
      chronic fatigue syndrome].
AB  - OBJECTIVE: To search for an effective therapy for chronic fatigue syndrome (CFS).
      METHODS: Eighty-five cases of CFS were treated with massage and pressing of Back
      shu points, combined with pressing acupoints on the head. The therapeutic effect
      was observed. RESULTS: After treatment of 3 courses, 26 cases were markedly
      effective, 52 cases were effective, and 7 cases were ineffective, with a total
      effective rate of 91.8% and a markedly effective rate of 30.6%. CONCLUSION:
      Pressing acupoints and massage can effectively improve clinical symptoms of the
      patient with chronic fatigue syndrome.

PMID- 18085146
TI  - [Standard expression of indications of acupoints].
AB  - The present paper systematically investigates basic characteristics and
      development law of acupoint indication expression, and put forward on the basis
      that expression standards based on standardization, expression style of acupoint
      indication expression reflecting acup-moxibustion own law, that is, summarization
      by treatment ranges and expression style by example of typical diseases.

PMID- 18085147
TI  - [Measurement and analysis of acupuncture manipulation].
AB  - Acupuncture manipulation is an important part of the theory of acupuncture and
      moxibustion, and it is a basic skill for acupuncture physicians. In order to
      further disclose the essence and character of acupuncture manipulation, the
      scholars collect in time acupuncture manipulations by the multi-subject crossing
      methods for qualitative, quantitative analysis and study, and make its analysis
      of dynamics and kinematics with the riper engineering. However, the current study
      and analysis on acupuncture manipulation is not deep and not systemic, so the
      thesis proposes a research way which should create a database of the acupuncture
      manipulation, so as to provide reliable evidences for studies of correlativity
      between acupuncture manipulation and acupuncture effects, and establish the
      theoretical basis for the study of the quantification and standardization of
      acupuncture manipulation.

PMID- 18085148
TI  - [Study on effect of electroacupuncture on gastric ischemia-reperfusion by laser
      Doppler blood perfusion imaging].
AB  - OBJECTIVE: To observe effects of electroacupuncture (EA) on gastric blood
      perfusion and search for a study method reflecting changes of blood perfusion.
      METHODS: On the basis of establishing a new gastric ischemia-reperfusion model
      which was made by ligature of gastric right artery, EA was given at "Zusanli" (ST
      36) and the gastric blood perfusion images were displayed by a laser Doppler
      blood perfusion imager (LDPI), and effects of EA on gastric blood perfusion were
      analyzed. RESULTS: (1) The image of the gastric ischemia-reperfusion is clear.
      The ischemic degree of the stomach in the EA group was lower than the control
      group within 30 min of ischemia, and recovery of blood flow after perfusion in
      the EA group was better than the control group; (2) at 25 min of ligature, there
      was a significant difference in changes of blood perfusion between the EA group
      [(-0.50 +/- 0.18) PU] and the control group [(-0.90 +/- 0.16) PU], P < 0.05.
      CONCLUSION: EA can improve and promote gastric blood supply in the gastric
      ischemia-reperfusion model, which can be used for acupuncture and moxibustion
      experimental study.

PMID- 18085149
TI  - [Study on dual-directional regulation induced by acupuncture at different
      acupoints in the rat with motility abnormality of the stomach].
AB  - OBJECTIVE: To probe into the bidirectional regulation of acupuncture in the rat
      with motility abnormality of the stomach and the nerve mechanism. METHODS:
      Adopting electrophysiological methods, the extracellular discharge signals of
      neuronic action in NTS were recorded with glass microelectrodes. The effects of
      acupuncture at "Zusanli" (ST 36), "Neiguan" (PC 6), "Zhongwan" (CV 12), "Qihai"
      (CV 6) on discharges of NTS neurons and intra-gastric pressure were observed in
      the rat at normal physiological state, and increase or reduction of gastric
      motility. RESULTS: Acupuncture at "Zusanli" (ST 36), "Neiguan" (PC 6) could
      significantly promote gastric motility of the rat at normal status, increase or
      reduction of gastric motion, while acupuncture at "Zhongwan" (CV 12), "Qihai" (CV
      6) could significantly inhibit gastric motion. And acupuncture at all the above
      acupoints could activate discharges of NTS neurons. CONCLUSION: The bidirectional
      regulation effect of an acupoint does not certainly indicate that the same point
      has bidirectional regulation effect on an internal organs at different
      pathological states, while this may show synthetic action of different points
      which is a good regulation towards normal states and homeostasis.

PMID- 18085150
TI  - [Comrade ZHU Lian, a pioneer and innovator of acupuncture and moxibustion science
      in new China].
AB  - Comrade ZHU Lian is a main founder of Institute of Acupuncture and Moxibustion,
      China Academy of Chinese Medical Sciences, and she is the first to learn TCM for
      a physician of western medicine. The present paper looks back the works of
      comrade ZHU in acupuncture and moxibustion cause. Her main contributions are
      learning acupuncture and moxibustion medicine, popularizing acupuncture and
      moxibustion therapy; being concerned acupuncture and moxibustion cause,
      establishing organization of acupuncture and moxibustion research, more early
      conducting international exchanges of acupuncture and moxibustion; paying
      attention to clinical practice, proposing scientific research of acupuncture and
      moxibustion; writing New Acupuncture and Moxibustion Science, passing on later
      generations.

PMID- 18085151
TI  - [Modern expression of classical acupuncture and moxibustion theories].
AB  - Times differences of expression language and language situation of the classical
      acupuncture and moxibustion theories as the crux of acup-moxibustion science
      hinder understanding and exchanging of modern people. According to characters of
      acupuncture and moxibustion language, modern language expression of acupuncture
      and moxibustion theories based on systematical studies of writing, theoretical
      system, ideological concept and method of thinking is a basic prerequisite for
      inheritance and development of acupuncture and moxibustion science in the present
      ages.

PMID- 18085152
TI  - [Professor OUYANG Qun's clinical experience on application of single point].
AB  - The clinical experience of Professor OUYANG Qun in using single acupoint includes
      treatment of Meniere's syndrome with Baihui (GV 20), optic neuritis with
      "Fengyan" (Extra point), painful heel with Xiaguan (ST 7), lymphoid tuberculosis
      with Quchi (LI 11), acute sore throat with Kongzui (LU 6), painful diseases with
      "Luolingwu" (Extra point), chest distress with "Kuanxiong" (Extra point),
      hordeolum with Feishu (BL 13), headache in menstrual period with Xuehai (SP 10),
      frozen shoulder with Tiaokou (ST 38), toothache with Waihuaijian (Extra point),
      occipital pain with Chengshan (BL 57) and vomiting with Yongquan (KI 1).

PMID- 18085153
TI  - [Randomized and controlled observation on acupuncture and moxibustion combined
      with western medicine for treatment of malaria of children in Africa].
AB  - OBJECTIVE: To compare therapeutic effects of acup-moxibustion combined with
      western medicine and simple western medicine on child malaria in Africa. METHODS:
      One hundred and thirty-two cases were randomly divided into an acup-moxibustion
      plus western medicine group (n = 67) and a western medication group (n = 65). The
      western medication group were treated with Quinoline and expectant therapy, and
      the acup-moxibustion plus western medicine group with acup-moxibustion plus the
      western medicines as those in the western medication group, and the therapeutic
      course was one week. Main clinical manifestations and lab examinations for
      malaria were compared. RESULTS: The total effective rate was 97.0% in the acup
      moxibustion plus western medicine group and 95.4% in the western medication
      group, with a significant difference between the two groups (P < 0.05); the acup
      moxibustion plus western medicine group in decreasing fever of the patient and
      the density of malarial parasite in blood, shorting the duration of illness and
      recovery time of RBC was significantly better than the western medication group
      (P < 0.05). CONCLUSION: Clinical therapeutic effect of acup-moxibustion combined
      with western medicine is better than that of simple western medicine.

PMID- 18085154
TI  - [Bibliometric analysis of literature on acupuncture and moxibustion for treatment
      of knee osteoarthritis].
AB  - OBJECTIVE: To reflect present situation of studies on acupuncture and moxibustion
      for treatment of knee osteoarthritis (KOA), so as to provide thinking and
      evidence for further studies. METHODS: Quantitative analysis on acupuncture and
      moxibustion treatment of KOA is carried out with bibliometric method, using CNKI
      as data resource. RESULTS: Altogether 98 papers are effective, which are
      published on 48 journals; more clinical studies are involved; combined therapy is
      commonly-uesd method, and Yanglingquan (GB 34), Xuehai (SP 10), Neixiyan (EX-LE
      4), Dubi (ST 35) are commonly-used acupoints. CONCLUSION: The level of clinical
      study on acupuncture and moxibustion treatment of KOA is lower; studies on the
      mechanism are insufficient; it is suggested that studies on the best combined
      program of comprehensive treatment ways need to be further strengthened.

PMID- 18085155
TI  - [See symptoms and signs of six channels of feet in Huangdi's Internal Classic
      from medical books of bamboo slips and silk cloth].
AB  - Some champers besides Miraculous Pivot: Channels and Vessels in Huangdi's
      Internal Classic are involved in diseases of channels and vessels, and most of
      them which mainly discuss diseases of channels and vessels are explained in the
      type of six channels of feet. Studies have showed that the diseases of six
      channels of the feet are closely related with diseases of channels and vessels in
      the medical books of bamboo slips and silk cloth, indicating that on the one
      hand, the studies on diseases of channels and vessels are not only limited in
      Miraculous Pivot: Channels and Vessels, and on the other hand, the influence of
      the literature of channels and vessels in the medical books of bamboo slips and
      silk cloth is quite profound and lasting. Widening the field of vision of
      investigating concept of diseases of channels and vessels, and looking closely at
      the course of history from academic development are favorable to deeply
      understanding diseases of channels and vessels, even early theories of channels
      and vessels.

PMID- 18085156
TI  - Stress responses in adult cattle due to surgical dehorning using three different
      types of anaesthesia.
AB  - Dehorning adult cattle is a surgical procedure causing distress of varying
      intensities that can be reflected in behavioural changes and alterations in
      plasma cortisol levels. Stress responses during the dehorning process were
      evaluated in 18 Red Pied cows. The cows were divided into 3 groups of six and
      kept in tie-stall housing. Those in the first group were dehorned under general
      anaesthesia (GA) induced by intravenous administration of xylazine and ketamine.
      The second group was dehorned under sedation and local anaesthesia (SLA) induced
      by intramuscular administration of xylazine and local anaesthesia with lidocaine.
      The third group was dehorned under local anaesthesia (LA) with lidocaine.
      Dehorning was performed with a foetotomy wire. Blood samples were taken 0.5 h
      before dehorning to determine cortisol levels, and, by means of a central venous
      catheter inserted into the jugular vein, during surgery at 0, 0.5, 1, 1.5, 2,
      2.5, 3, 3.5, 4, 5, 6, 7 and 8 h post-surgery. Concurrently, occurrence of stress
      behaviours was assessed. Cortisol levels were measured by enzyme immunoassay
      (EIA). The lowest mean peak levels of plasma cortisol (82.53 +/- 6.04 nmol l(
      1)), the most rapid return of plasma cortisol levels to baseline values (1.92 +/-
      1.11 h), and the lowest occurrence of stress behaviours (2.38 +/- 5.83%) were
      noted in the SLA group. The highest mean peak levels plasma cortisol (113.86 +/-
      25.65 nmol l(-1)), the slowest return of plasma cortisol levels to baseline
      values (3.83 +/- 2.18 h) and the most frequent occurrence of stress behaviours
      (65.48 +/- 28.72%) were observed in the LA group. There were significant
      differences between the SLA and LA groups in peak plasma cortisol levels (p =
      0.011) and in occurrence of stress behaviours (p = 0.003). Sedation induced by
      intramuscular administration of xylazine in conjunction with local anaesthesia
      with lidocaine is considered the most suitable method of anaesthesia when
      dehorning adult cattle. Local anaesthesia with lidocaine alone was least
      suitable.

PMID- 18085157
TI  - [PRRSV-eradication: an option for pig herds in Germany?].
AB  - The problem of successfully controling PRRS with traditional methods has led to a
      growing interest in eradication. This review summarizes the current literature on
      topics of PRRS-eradication, including the relevant routine diagnostic procedures,
      routes of virus transmission between pig herds (as i.e. pig movement, semen,
      aerosols, insects, fomites, transport vehicles) and eradication by close&rollover
      and test&removal, respectively. On the basis of this knowledge and experiences it
      can be concluded that PRRS eradication in Germany with its intensive pig
      production and remarkably high pig density in several regions may only be
      possible through a national eradication program. The lack of potent marker
      vaccines that reduce the virus spread significantly, combined with the lack of
      differentiating diagnostic tests for routine laboratory use leads to the
      recommendation not to launch a national eradication program under the given
      circumstances. For the future it should be taken into account that the situation
      after reintroduction of PRRSV in a free region could only be managed by stamping
      out which is generally poorly accepted by the majority of pig producers.

PMID- 18085158
TI  - A live bovine herpesvirus-1 marker vaccine is not shed after intramuscular
      vaccination.
AB  - It should be established, whether animals vaccinated intramuscularly (IM) with a
      live Bovine herpesvirus type 1 (BHV-1) marker vaccine become viremic and/or
      excrete vaccine virus with nasal discharge. Five cattle, seronegative for BHV-1,
      were vaccinated with an overdose of the vaccine (Bovilis IBR marker live) via the
      IM route. Nasal swabs and blood samples were taken at regular intervals and
      tested for BHV-1 in a virus infectivity assay. In addition, a polymerase chain
      reaction (PCR) specific for BHV-1 DNA was performed on the blood samples. BHV-1
      neutralizing antibody titres were determined in the sera taken prior to the
      vaccination and four weeks after immunisation. AIl animals were successfully
      vaccinated as judged by the development of BHV-1 neutralising antibodies.
      However, all nasal swab samples were tested negative for vaccine virus, and all
      blood samples were found negative for BHV-1 vaccine virus and BHV-1 specific DNA.
      From these data it can be concluded that the vaccine virus was not excreted with
      nasal discharge after IM vaccination and that the vaccinated animals did not have
      a detectable viremia. Therefore, it is recommended to apply the tested BHV-1
      marker live vaccine by the IM route in situations where it is undesirable that
      the vaccine virus is excreted.

PMID- 18085159
TI  - [Frequency of occurrence of pneumonia associated agents and their correlation
      with clinical and pathological-anatomical findings in pigs].
AB  - The aim of this study was to investigate the incidence and influence of different
      causative organisms involved in the development of pneumonia and bronchopneumonia
      in pigs. Bronchoalveolar lavage fluid (BALF) from 339 pigs was examined molecular
      biologically and culturally. The evaluation considered the following pathogens:
      Mycoplasma (M.) hyopneumoniae, Mycoplasma (M.) hyorhinis, PRRSV (US-Type), PRRSV
      (EU-Type), PCV-2, Influenzavirus Type A, alpha-haemolytic Streptococci, beta
      haemolytic Streptococci, Pasteurella (P.) multocida, Bordetella (B.)
      bronchiseptica, Haemophilus (H.) parasuis and Actinobacillus (A.)
      pleuropneumoniae. This was followed by a pathological-anatomical examination in
      168 pigs. Pathological-anatomical examination was evaluated for possible
      interstitial pneumonia, catarrhal-purulent bronchopneumonia and pleuritis. alpha
      haemolytic Streptococci, PCV-2, H. parasuis, M. hyorhinis, M. hyopneumoniae, B.
      bronchiseptica, PRRSV (US-Type), P. multocida, PRRSV (EU-Type) and Influenzavirus
      Type A were evident in descending incidence in the BALF. A. pleuropneumoniae were
      only isolated culturally in two cases in the BALF. The frequency and
      semiquantitative detection rate in the bacteriological culture of alpha
      haemolytic Steptococci, M. hyopneumoniae, P. multocida and B. bronchiseptica
      correlated significantly with the ascertained clinical evaluation score and the
      pathological-anatomical examination score. M. hyorhinis and Influenzavirus Type A
      only correlated with the severity degree of clinical appearance, while PCV-2 and
      PRRSV (US-Type) correlated with the frequency of pathological-anatomical changes.
      The higher the clinical score, the higher was the number of animals ascertained
      with five or more different pathogens. The more different causal agents were
      isolated in the BALF of one animal, the higher was the average pathological
      anatomical examination score. For the diagnosis of pneumonia, especially when
      analysing facultative pathogens or secondary pathogens, a useful interpretation
      of analysis results is only possible in connection with a clinical and
      pathological evaluation.

PMID- 18085160
TI  - Analysis of systematic and genetic effects on the prevalence of primary cataract,
      persistent pupillary membrane and distichiasis in the two color variants of
      English Cocker Spaniels in Germany.
AB  - Genetic parameters were estimated for prevalences of primary cataract (CAT),
      persistent pupillary membrane (PPM) and distichiasis (DIST) in 615 single-colored
      and 617 multi-colored English Cocker Spaniels (ECS) bred in the German kennel
      club for Spaniels (Jagdspaniel-Klub e.V.). CAT or CAT diagnosed in dogs up to
      three and a half years of age (early-onset cataract, CAT-early) and CAT diagnosed
      in dogs over three and a half years of age (late-onset cataract, CAT-late), PPM
      and DIST were included as binary traits in multivariate genetic analyses.
      Heritabilities on the underlying liability scale were 0.15 for CAT, 0.34 for CAT
      early, 0.13 for CAT-late, 0.46 for PPM, and 0.62 for DIST in single-colored ECS
      and 0.06 for CAT, 0.13 for CAT-early, 0.14 for CAT-late, 0.10 for PPM, and 0.61
      for DIST in multi-colored ECS. There were indications for a different genetic
      basis of CAT-early and CAT-late in single-colored ECS as genetic correlations
      were close to zero. In multi-colored ECS, a similar tendency for CAT-early and
      CAT-late could be observed.

PMID- 18085161
TI  - [Literature review of the diagnosis of porcine proliferative enteropathy].
AB  - Lawsonia (L.) intracellularis is the etiologic agent of ileitis, which occurs in
      different forms in pigs. The infection can be demonstrated by several methods. In
      routine diagnosis the indirect detection of L. intracellularis is conducted by
      measuring antibodies performing an indirect IFT or ELISA. Furthermore, an IFT and
      PCR on faecal and/or tissue samples are well established for the direct
      detection. The suitability of PCR on faecal samples is frequently discussed.
      Problems are related to various inhibitors that are component of faeces. When
      interpreting laboratory results, the past medical history of pigs, i.e.
      antimicrobial treatment, has to be considered. Since 2004 a new vaccine against
      ileitis is licensed. A possible influence of vaccination on diagnostic testing,
      especially PCR and ELISA, is hardly investigated. Therefore, the interpretation
      of laboratory results from vaccinated animals is, considering the current
      literature, restrained.

PMID- 18085162
TI  - [Congenital malformation of the front limbs in a llama (Lama glama): polydactyly
      in combination with arthrogryposis].
AB  - A male, 10 month old llama with malformation of both front limbs was presented.
      Both front limbs had one more digit located medially. The distal phalanx of this
      additional digit at the left front limb reached the ground by the tip of the
      keratinzed pad and the toenail. The accessory digit at the right front limb was
      bent in a 90 degree angle caudolateraly. Beside the digital bones of the
      accessory digits the second metacarpal bone and the first carpal bone could be
      detected in both front limbs by radiological examination. Secondary a bilateral
      slight carpal valgus deformity could be seen.

PMID- 18085163
TI  - Evaluation of the low-dose dexamethasone suppression test and ultrasonographic
      measurements of the adrenal glands in cats with diabetes mellitus.
AB  - The objectives of the study were to evaluate the low-dose dexamethasone
      suppression (LDDS) test and the size of the adrenal glands via ultrasonography in
      cats with diabetes mellitus. Twenty-two cats were enrolled in the study. In 19
      cats, suppression of cortisol concentrations below 5.5 nmol/litre occurred four
      and eight hours after intravenous administration of dexamethasone (0.1 mg/kg). In
      one other cat, the cortisol concentration was also below 5.5 nmol/litre at eight
      hours but was 11.0 nmol/litre at four hours. The results were in agreement with
      those of healthy cats in a previous study. The cortisol concentrations four and
      eight hours after administration of dexamethasone did not differ between cats
      with good glycemic control (n = 8) and those with moderate to poor control (n =
      12). The adrenal glands of the diabetic cats were not enlarged compared with
      those of healthy cats. In two diabetic cats, the LDDS test results were abnormal.
      One cat had a pituitary adenoma and adrenal glands of normal size as determined
      by ultrasonography. The size of the adrenal glands of the other cat clearly
      differed; histological examination of the larger adrenal gland revealed an
      adrenocortical adenoma. Based on our findings, the results of the LDDS test using
      0.1 mg/kg of dexamethasone are normal in cats with diabetes mellitus independent
      of the quality of glycemic control. In addition, diabetes mellitus does not lead
      to a measurable increase in the size of the adrenal glands in cats. Further
      studies are needed to evaluate if the dexamethasone dosage used in this study is
      useful to diagnose mild form of hypercortisolism.

PMID- 18085164
TI  - [Avian influenza: wildbird monitoring in Switzerland between 2003-2006].
AB  - During various surveillance programs more than 3500 cloacal swabs and organ
      samples from songbirds, waterbirds and poultry have been tested for avian
      influenza using real time RT-PCR. Switzerland carried out the first wildbird
      monitoring between autumn 2003 and spring 2005. 1053 samples, mostly from
      songbirds, were tested. LPAI-strains were found in two cases. A second
      intensified surveillance program started in October 2005 along with the first ban
      on free range poultry farming. Until the end of April 2006 2455 cloacal swabs
      from dead wildbirds have been analysed. By the end of february H5N1 was for the
      first time detected in Switzerland and by the end of march 32 waterbirds have
      been found positive for H5N1. 146 poultry flocks with a special permission for
      free range management proved to be AI negative.

PMID- 18085165
TI  - [Acute idiopathic hypereosinophilic syndrome in a rottweiler].
AB  - The idiopathic hypereosinophilic syndrome is a part of the yet rather unknown
      diseases and the aetiology remains at the least hypothetical. This syndrome is
      characterized by a variable hypereosinophilemia as well as a massive infiltration
      of several organs by mature eosinophils, causing an important tissue damage
      leading to organ dysfunctions and resulting in the patient death. In this
      reported case, the acute idiopathic hypereosinophilic syndrome was diagnosed in a
      4-year rottweiler female dog based on an increased eosinophilemia and the
      infiltration of stomach, small intestine, colon, pancreas, spleen, ganglions,
      skin, lungs and bone marrow by mature eosinophiles. The acute development of the
      disease precluded any therapeutical hope success.

PMID- 18085166
TI  - [Carbofuran poisoning in mallard ducks].
AB  - Carbofurane, a pesticide from the group of carbamates, has been employed against
      soil nematodes on a small meadow at the lake of Lugano, Switzerland. On the next
      morning, the first cases of death involving a total of 19 mallard ducks (Anas
      platyrhynchos) have been reported. By inhibiting the enzymatic breakdown of the
      neurotransmitter acetycholine, carbamates lead to excessive activation of the
      parasympathicus. In addition, paralysis of skeletal muscles is caused by
      continued stimulation of neuromuscular junctions. Death may occur by asphyxia. In
      the present case report, the diagnosis of poisoning could be confirmed by the
      chemical detection of carbofuran in the stomach, blood, muscle and kidney tissue
      of the affected mallard ducks.

PMID- 18085167
TI  - Recent histopathological studies in leprosy, with particular reference to early
      diagnosis and leprous neuropathy.
AB  - In histopathological studies in leprosy, two important areas were identified in
      recently published work. They are early diagnosis and neuropathy. In
      histopathological examination, finding of M. leprae in tissues and/or
      granulomatous destruction of nerves are the two important findings to confirm the
      diagnosis. Immunopathological staining of M. leprae, PCR amplification of M.
      leprae antigen and S100 staining of Schwaann cells have considerably enhanced the
      sensitivity of histopathological diagnosis. If the two clinical findings such as
      hypopigmented patches with impaired sensation and thickened nerves accompanied by
      loss of sensation are the only ones that are taken into account for diagnosis,
      then a significant number of early patients will be missed. It is pointed out
      that biopsy examination of skin and nerves, when necessary, and skin-smear
      studies are indispensable diagnostic procedures. In the study of leprous
      neuropathy, there are several studies trying to decipher the entry of M. leprae
      into Schwann cells. The sharing of antigens between M. leprae and surface
      membrane of Schwann cells may be an important factor. However, there is much more
      to be learned in this area. In the control and prevention of neuritis, although
      corticosteroids administered along with multi-drug therapy was helpful, the
      benefit was not sustained.

PMID- 18085168
TI  - Recent advances in immunodiagnosis of leprosy.
AB  - Although prevalence of leprosy is considerably reduced, the unabated emergence of
      about 300,000 cases worldwide indicates that the source of infection and
      transmission are not being addressed. Early diagnosis and treatment still remain
      the cornerstone of leprosy control. Many diagnostic issues hinder the correct and
      timely diagnosis and classification of leprosy. Delayed and missed diagnosis of
      infectious leprosy patients and the lack of tests to measure asymptomatic M.
      leprae infection in contacts also hamper the assessment of transmission of M.
      leprae infection. An important goal would be the development of improved
      diagnostic tools to diagnose difficult cases and to detect M. leprae infection
      before clinical manifestation. The search for an ideal immunodiagnostic tool for
      leprosy had gone through various phases and development over the years, with
      inherent limitations in the sensitivity and specificity of the immunodiagnostic
      tests for leprosy. With improvement in technology many modifications of
      previously used PGL-1 assay in the form of rapid and less expensive techniques,
      such as dipstick, ELISA, ML flow test, have been introduced. Many new skin test
      antigens with potential for improving their efficiency, such as MLSA LAM, MLCwA
      and their fractionates, have been studied. After the completion of genome
      sequencing of M. leprae in 2000, many genes that were studied in M. tuberculosis
      and found potential for the immunodiagnosis of tuberculosis, such as CFP-10 and
      ESAT-6 proteins, have been investigated in M. leprae also. Genes that are unique
      to M. leprae with no homologous in M. tuberculosis have been explored for novel
      M. leprae-specific antigens. In order to overcome the problem of cross
      reactivity, a number of workers have synthesized overlapping short peptides of
      different M. leprae recombinant proteins and studied their sequence divergence
      and attempted to identify M. leprae-specific B- and T-cell epitopes. This review
      makes an effort to present an overview of all these developments in the field of
      immunodiagnosis of leprosy.

PMID- 18085169
TI  - Recent developments in elimination of leprosy in India.

PMID- 18085170
TI  - Advances in the treatment of reactions in leprosy.
AB  - Morbidity in leprosy is almost always due to reactions. Similarly, to a great
      extent, deformities in leprosy are the consequence of reactions occurring both in
      borderline patients (type 1 or reversal reactions) and in lepromatous patients
      (type 2 or ENL reactions). Over the last three decades, work has centred around
      finding who are prone to getting the reactions, identifying the risk factors and
      improving the management of reactions in order to alleviate quickly the suffering
      and prevent and reverse nerve damage consequent to reactions. Though several new
      drugs have been tried and found somewhat useful, corticosteroids and thalidomide
      continue to be the mainstay in the management of leprosy reactions. A brief
      review of the current understanding is presented.

PMID- 18085171
TI  - Recent advances in ocular leprosy.
AB  - Proper MDT soon after detection of leprosy and anti-reaction measures with newer
      steroids, regular supervision and monitoring of those released from treatment
      (RFT) reduce the incidence of ocular leprosy to a remarkable extent. Today, most
      eye complications are because of normal ageing process or of other phenomena in
      normal healthy population. Cataract and lagophthalmos are the main causes of
      blindness. However, in India, though the rate of cataract surgical coverage is up
      to the mark, the same for lagophthalmos is lagging far behind. Integration of
      management of ocular leprosy into community eye health care service is the talk
      of the day along with other health care facilities delivered to people affected
      with leprosy (PAL). Routine eye examinations are necessary for all PB and MB
      patients, as well as for the RFT persons in order to detect and treat eyes that
      are at high risk. All eye surgeries can be performed when needed, irrespective of
      deformities and bacteriological status, by latest microsurgical techniques with
      good outcome, and better rehabilitation measures. Reorientation training in
      ocular leprosy is the immediate special need for ophthalmologists, paramedical
      ophthalmic assistants and eye health care managers working in general hospitals
      in those areas that were previously "leprosy endemic zones".

PMID- 18085172
TI  - Recent advances in molecular biology of leprosy.
AB  - The last three decades have witnessed rapid progress in understanding the
      molecular biology of Mycobacterium leprae. Following the availability of complete
      genome sequence of leprosy bacillus in 2001, things have drastically changed.
      With the information about genetic structure, several techniques have been
      developed for diagnosis, molecular epidemiology and also detection of drug
      resistance. With the decline in the prevalence of leprosy globally, there has
      been some reduction in interest in the molecular methods for diagnosis, yet
      molecular techniques for studying the transmission dynamics and detection of drug
      resistance continue to be relevant. Knowledge about complete genome sequence has
      made it possible to undertake studies that can improve our understanding of the
      structure and function of this enigmatic organism. Newer information emerging
      about biology of M. leprae would provide insight into mechanisms of its survival
      and persistence in host and is likely to lead to better diagnostics and also
      therapeutics for mycobacterial infections in general.

PMID- 18085173
TI  - [Abortion and stillbirth among dairy goats as a consequence of Coxiella
      burnetii].
AB  - The clinical signs and pathological findings of clinical Q fever in dairy goats
      in the Netherlands are described. The disease is characterized by endemic or
      epidemic abortion in late pregnancy, stillbirth, or the birth of weak kids. These
      consequences of Coxiella burnetii infection appear to have increased during
      recent years in the Dutch dairy goat population. Detection of the agent in
      placental tissue by immunohistochemistry has proven diagnostically useful.

PMID- 18085174
TI  - [Q fever: an overview].
AB  - Q fever, a zoonosis caused by the gram-negative bacterium Coxiella burnetii,
      occurs worldwide and affects both humans and animals. Ruminants are considered to
      be the main source of infection of humans, with the main route of infection being
      through inhalation of the organism of fine-particle aerosols. Abortion is the
      main clinical sign in ruminants. During and after abortion, large quantities of
      the bacterium are shed via the placenta and other vaginal secretions. The
      bacterium may also be present in faeces and milk. The bacterium can survive for a
      long time in the environment after shedding and can be spread over long
      distances. Seroprevalence among cattle is rather high in the Netherlands and in
      many other countries. Infection is diagnosed by detecting antibodies against the
      bacterium or the bacterium itself by means of a PCR method. The efficacy of using
      antibiotics or vaccines for treatment or prevention of the disease in cattle is
      still unclear and there are currently no effective disease control programmes.

PMID- 18085175
TI  - [Hepatocutaneous syndrome].

PMID- 18085176
TI  - [Kennel spasms].

PMID- 18085177
TI  - [Six years of chairmanship and the Journal of Veterinary Medicine].

PMID- 18085178
TI  - [One window for information about domestic animals].

PMID- 18085179
TI  - [Juvenile castration of kittens remains a must].

PMID- 18085180
TI  - [News from the AUV Veterinary Media Library].

PMID- 18085181
TI  - [Is quality still important?].

PMID- 18085182
TI  - [Summary of the First International Conference on Contagious Equine Metritis].

PMID- 18085183
TI  - [WAAVP-congress 'Advancement in Parasitology' in Ghent, Belgium, August 19-23
      2007].

PMID- 18085184
TI  - [SEVC Barcelona, Spain exceeds expectations].

PMID- 18085185
TI  - Pseudo-cysts, lipomas, infarcts and simple cysts of the calcaneus: are there
      different or related lesions?
AB  - Pseudocysts, lipomas, infarcts and simple cysts of the calcaneus are described as
      different entities in the medical literature. However, some evolutions or
      associations may suggest a relationship which is not yet demonstrated in all
      cases. The aim of this article is to describe each lesion and emphasize their
      different characteristics that may suggest a relationship between them.

PMID- 18085186
TI  - Ultrasound of the shoulder.
AB  - Ultrasound has been widely used for the evaluation of the shoulder, mainly for
      rotator cuff pathology. Developments in technology, as well as better knowledge
      of the pathology and the anatomy make this examination one of the most useful in
      the exploration of the shoulder, especially in the hands of the experienced
      radiologist. Ultrasound is low-cost, readily available and should be considered
      with plain films as the first step examination of the shoulder. Ultrasound is not
      only useful for the evaluation of the rotator cuff pathology and impingement
      syndrome, but is also performing in the evaluation of non rotator cuff pathology
      such as biceps tendon pathology, shoulder instability, mass evaluation,
      infection, degenerative and inflammatory arthropathies and nerve entrapment
      syndromes. Making a complete evaluation of the shoulder helps to differentiate
      between rotator cuff pathology and others that can mimic rotator cuff disorders.
      This article will review shoulder anatomy and examination technique and the
      different pathologies that can be assessed by ultrasound.

PMID- 18085187
TI  - MR arthrography of the rotator cuff.
AB  - This article addresses the role of MR arthrography in the evaluation of the
      rotator cuff, including impingement, tendon degeneration and rotator cuff tears.
      Additionally, pathologic conditions of the long head of the biceps tendon, and
      mimickers of rotator cuff pathology are discussed as well. The drawbacks of
      conventional MR imaging and indirect MR arthrography, compared to the merit of
      direct MR arthrography are emphasized. The manuscript focusses on the potential
      clinical consequences of each finding and summarizes which relevant imaging
      findings should be reported by the radiologist.

PMID- 18085188
TI  - Reduction of metal artefacts in musculoskeletal MR imaging.
AB  - The purpose of this article is to present a educational overview of practical
      tips to deal with metal artefacts in clinical musculoskeletal MRI. A brief
      theoretical explanation to understand the cause of metal artefacts is provided
      followed by a discussion on parameters to reduce these metal artefacts. Effects
      of adjustable parameters are demonstrated both in a volunteer with a titanium
      screw and a saline bag attached to the shoulder and in a in vitro experiment.
      These parameters include positioning of the patient with the long axis of
      metallic hardware parallel to B0, use of fast spin echo sequences, use of
      inversion recovery fat suppression, swapping phase and frequency encoding
      direction, use of view angle tilting, increasing the read-out bandwidth, and
      decreasing voxel size.

PMID- 18085189
TI  - Bone marrow edema of the femoral head.
AB  - This article addresses the MR features of the bone marrow edema syndrome (BMES)
      of the femoral head with emphasis on the prevalence and clinicopathology of the
      disorder and description of the current concepts on diagnosis and prognosis. BMES
      can be observed in self resolving conditions such as transient osteoporosis of
      the hip, spontaneous fracture of the femoral head, or post traumatic lesions.
      Rapidly destructive coxarthrosis, necrosis of the femoral head as well as certain
      forms of spontaneous fracture of the femoral head may present a similar MR
      pattern, though prognosis is definitely less favourable. The challenging role of
      the radiologist is to recognize BMES at an early stage and to provide adequate
      prognosis on the lesion outcome.

PMID- 18085190
TI  - [Principles of analysis for sacroiliac joints imaging].
AB  - Interpretation of sacroiliac joints imaging is uneasy. Simultaneous erosions,
      hyperostosis, and ankylosis together make the diagnosis of inflammatory lesions.
      Articular abnormalities may also be induced by mechanical stress or ligament
      ossifications. Distribution of the lesions can help to establish a precise
      diagnosis. Inflammatory lesions may be located in any part of the articulation,
      including the posterior and inferior part. Mechanical lesions as in osteitis
      condensans ilii are commonly located in the anterior middle part of the joint.
      Ligament ossification in case of idiopathic skeletal hyperostosis is located at
      the margins of joint. The basic for the interpretation of sacroiliac joints is to
      look at high quality plain radiographs. When diagnosis is uncertain,
      complementary methods must be considered. CT is useful for analysis of subacute
      or chronic lesions and MRI is to be preferred for acute lesions, in young
      patients and when searching for signs of inflammatory activity in an already
      known chronic disease.

PMID- 18085191
TI  - Ewing's sarcoma: imaging features.
AB  - AIM: To define an imaging prototype of Ewing's sarcoma (ES). MATERIALS AND
      METHODS: Sixty-four patients with a histopathologically and/or genetically proven
      diagnosis of ES were analyzed for clinical parameters (age, gender and location),
      radiographic and CT appearance (distribution, matrix, margins, periosteal
      reaction, articular extension, cortical reaction and the presence of a pathologic
      fracture). Size, local extension, signal intensity, degree and pattern of
      enhancement, and the presence of skip metastases were evaluated on MRI. Distant
      metastases were recorded on bone scintigraphy and chest CT scan. RESULTS:
      Patient's age ranged between 7-67 (mean 17.9). Male/female ratio was 2.4/1.
      Location in the pelvis was most frequent (31%), followed by the femur (20%) and
      tibia (11%). Most tumors were mixed lytic-sclerotic (75%), and purely lytic in
      25%. Plain films and CT scan showed a spiculated periosteal reaction in 50%. A
      Codman's triangle was seen in 27%. Articular extension was difficult to assess on
      radiographs. Cortical permeation and destruction is seen in respectively 31 and
      42%, whereas cortical thickening is seen in 20%. Pathologic fracture occurred in
      7.8%. MRI showed a large mass, with a soft tissue component of more than 50% in
      67%. Degree and pattern of enhancement pattern was variable. Signal intensity on
      T1- and T2-WI was non-specific. Joint involvement was seen in 23%. Isolated
      involvement of the soft tissue (extraskeletal ES) was seen in 1.5%. Skip
      metastases at initial presentation were present at initial presentation in 14%
      and distant metastases in 22%. CONCLUSIONS: ES occurs in young patients. On
      radiographs/CT, 37.5% are located in the axial skeleton and 62.5% in the
      peripheral skeleton. ES is mostly mixed sclerotic-lytic. A spiculated periosteal
      reaction is most frequent. The most characteristic finding on MRI is the presence
      of a large soft tissue mass.

PMID- 18085192
TI  - MR arthrography in glenohumeral instability.
AB  - The impact of accurate imaging in the work-up of patients with glenohumeral
      instability is high. Results of imaging may directly influence the surgeon's
      strategy to perform an arthroscopic or open treatment for (recurrent)
      instability. Magnetic resonance (MR) imaging, and MR arthrography in particular,
      is the optimal technique to detect, localize and characterize injuries of the
      capsular-labrum complex. Besides TI-weighted sequences with fat suppression in
      axial, oblique sagital and coronal directions, an additional series in abduction
      and exoroation position is highly advocated. This ABER series optimally depicts
      abnormalities of the inferior capsular-labrum complex and partial undersurface
      tears of the spinatus tendons. Knowledge of different anatomical variants that
      may mimic labral tears and of variants of the classic Bankart lesion are useful
      in the analysis of shoulder MR arthrograms in patients with glenohumeral
      instability.

PMID- 18085193
TI  - MR imaging findings in patients with a surgically significant mediopatellar
      plica.
AB  - PURPOSE: To identify MR imaging findings seen in patients with an
      arthroscopically confirmed significant plica. MATERIALS AND METHODS: MR and
      arthroscopy reports of 450 patients were reviewed. Nine patients were identified
      with an arthroscopically significant plica that was resected. Nine patients from
      these 450 were randomly chosen as a control group. Different criteria were
      evaluated on the MR images of all patients including: interposition of plica,
      number of slices with interposition, presence of fluid (focal or generalized),
      and thickening of the plica. RESULTS: Interposition was found on 3 to 10
      transverse imaging slices in the study group (mean, 5.9), and 1 to 4 imaging
      slices in the control group (mean, 3). Thickening was present in 4/9 patients of
      the study group and 2/9 patients in the control group. Focal fluid, out of
      proportion to fluid in the remainder of the joint was found in all patients of
      the study group and in none of the control group. CONCLUSION: Interposition of
      the plica on more than 5 transverse slices, and focal fluid adjacent to the plica
      may suggest the presence of a plica that will be considered significant at
      arthroscopy.

PMID- 18085194
TI  - Paget's disease with vanishing bone pattern and spinal fusion.
AB  - We present a rare case of Paget's disease involving the spine and pelvis, with
      unusual imaging features, including severe bony expansion and fatty infiltration,
      resulting in a "vanishing bone" appearance. Other rare imaging features are the
      presence of spinal and sacroiliac ankylosis.

PMID- 18085195
TI  - An unusual case of cat-scratch disease of the knee: case report and differential
      diagnosis.
AB  - We present a case of a 16-year-old boy with a painful swelling in the popliteal
      fossa, slight fever, articular and muscle pain of 3 weeks duration. Plain
      radiography and MR examination were performed in order to characterize the
      lesion. Additionally to the poorly defined mass, 2 satellite nodules were shown.
      Subsequent biopsy revealed a granulomatous process and 2 satellite
      lymphadenopathies highly suggestive of cat-scratch disease. This case shows that
      the differential diagnosis of a soft tissue mass of the knee should not only
      include tumoral processes or pseudotumoral lesions, but also granulomas from
      infectious or non-infectious origin. Knowledge of the patients contact with cats
      and the detection of skin scratches is usually the clue to the correct diagnosis.

PMID- 18085197
TI  - Bicipitoradial bursitis.

PMID- 18085196
TI  - Imaging of the hand, techniques and pathology: a pictorial essay.

PMID- 18085198
TI  - Nail patella syndrome.

PMID- 18085199
TI  - Spontaneous vertebral fracture: benign or pathological?

PMID- 18085200
TI  - In vitro expansion of tissue cells by conditional proliferation.
AB  - Cell therapies rely on the implantation of well-characterized functional cells
      with defined properties. Often, the cells of interest do not proliferate in vitro
      and thus cannot be expanded to the amount needed for characterization,
      purification, manipulation, or cloning. Here, we describe a method that allows
      the reversible expansion of cells by the introduction of a proliferator gene
      controlled by a regulatable expression module. The module is transferred by DNA
      transfer or by lentiviral transduction. The addition of a clinically accepted
      regulator [Doxycycline (Dox)] induces proliferator expression and expansion of
      the cells ad infinitum. Removal of the regulator eliminates the effect of the
      proliferator and leaves the cells in a non-proliferating status. The method has
      been applied to different mouse and human tissues. This chapter describes the
      method for the well-examined example of mouse embryonic fibroblast (MEF)
      expansion.

PMID- 18085201
TI  - Stem cell engineering using transducible Cre recombinase.
AB  - Embryonic stem (ES) cells have become a major focus of scientific interest both
      as a potential donor source for regenerative medicine and as a model system for
      tissue development and pathobiology. Tight and efficient methods for genetic
      engineering are required to exploit ES cells as disease models and to generate
      specific somatic phenotypes by lineage selection or instruction. In 1990s, the
      application of site-specific recombinases (SSRs) such as Cre has revolutionized
      mammalian genetics by providing a reliable and efficient means to delete, insert,
      invert, or exchange chromosomal DNA in a conditional manner. Despite these
      significant advances, the available technology still suffers from limitations,
      including unwanted side effects elicited by the random integration of Cre
      expression vectors and leak activity of inducible or presumptive cell type
      specific Cre expression systems. These challenges can be met by combining the
      Cre/loxP recombination system with direct intracellular delivery of Cre by
      protein transduction, thus enabling rapid and highly efficient conditional
      mutagenesis in ES cells and ES cell-derived somatic progeny. Modified recombinant
      variants of Cre protein induce recombination in virtually 100% of human ES (hES)
      and mouse ES (mES) cells. Here, we present methods for generating purified
      transducible Cre protein from Escherichia coli and its transduction into ES cells
      and their neural progeny.

PMID- 18085202
TI  - Human embryonic stem cells for tissue engineering.
AB  - Human embryonic stem cells (HESCs) are characterized by their ability to self
      renew and capacity to differentiate into almost every cell type. As a result,
      they have enormous potential for use in tissue engineering and transplantation
      therapy. If these cells can be induced to differentiate into a particular cell
      type, they may provide an almost unlimited source of cells for transplantation
      for treating certain diseases where normal cell function is impaired. The
      challenge lies in the development of techniques to induce differentiation into a
      specific cell type, to enrich for that population, and to isolate it. It is
      essential that the starting material, the undifferentiated embryonic stem cell
      line, is growing under optimal conditions that preserve its pluripotent potential
      and maintain a stable karyotype. This review will discuss methods for the growth,
      maintenance, and spontaneous differentiation of HESCs and methods to genetically
      manipulate them.

PMID- 18085203
TI  - Culture and characterization of human bone marrow mesenchymal stem cells.
AB  - Bone marrow (BM) mesenchymal stem cells (MSCs) are non-hematopoietic cells
      capable of generating colonies of plastic-adherent marrow mesenchymal cells, each
      derived from a single cell termed a colony-forming unit fibroblasts (CFU-Fs). In
      addition to their role in establishing the marrow microenvironment, these cells
      have been shown to differentiate into several types of mesenchymal and non
      mesenchymal lineages. Because of their multipotency, MSCs represent an attractive
      cellular source in the promising field of cellular therapy. In this chapter, we
      will focus on culture conditions for human BM MSC expansion and CFU-F assays. We
      also describe the methodologies to analyze the primary cultures obtained, both at
      the phenotypic and at the functional levels. Phenotypically, MSCs can be defined
      with a minimal set of markers as CD31-, CD34-, and CD45-negative cells and CD13-,
      CD29-, CD73-, CD90-, CD105-, and CD166-positive cells. Functionally, we describe
      the culture conditions (specific media and cellular preparations) for in vitro
      differentiation of MSCs into the adipogenic, osteogenic, and chondrogenic
      lineages. The corresponding colorimetric assays (oil red O, Von Kossa and
      alizarin red S, and safranin O and alcian blue stains, respectively) are also
      described.

PMID- 18085204
TI  - Skeletal ("mesenchymal") stem cells for tissue engineering.
AB  - Skeletal stem cells (SSCs, commonly referred to as "mesenchymal" stem cells) are
      found in the bone marrow stromal cell (BMSC) fraction of post-natal bone marrow.
      They can be isolated in culture as adherent, clonogenic cells endowed with the
      ability to grow and differentiate into multiple lineages, all of which correspond
      to tissues that are integral parts of the skeleton. The multipotency of SSCs is
      probed by in vivo transplantation assays. The ability of SSCs to generate a cell
      strain competent to form significant amounts of bone in vivo has led to the
      formulation of preclinical models of bone repair.

PMID- 18085205
TI  - Biomaterials/scaffolds. Design of bioactive, multiphasic PCL/collagen type I and
      type II-PCL-TCP/collagen composite scaffolds for functional tissue engineering of
      osteochondral repair tissue by using electrospinning and FDM techniques.
AB  - Current clinical therapies for traumatic or chronic injuries involving
      osteochondral tissue result in temporary pain reduction and filling of the defect
      but with biomechanically inferior repair tissue. Tissue engineering of
      osteochondral repair tissue using autologous cells and bioactive biomaterials has
      the potential to overcome the current limitations and results in native-like
      repair tissue with good integration capabilities. For this reason, we applied two
      modem biomaterial design techniques, namely, electrospinning and fused deposition
      modeling (FDM), to produce bioactive poly(epsilon-caprolactone)/collagen
      (PCL/Col) type I and type II-PCL-tri-calcium phosphate (TCP)/Col composites for
      precursor cell-based osteochondral repair. The application of these two design
      techniques (electrospinning and FDM) allowed us to specifically produce the a
      suitable three-dimensional (3D) environment for the cells to grow into a
      particular tissue (cartilage and bone) in vitro prior to in vivo implantation. We
      hypothesize that our new designed biomaterials, seeded with autologous bone
      marrow-derived precursor cells, in combination with bioreactor-stimulated cell
      culture techniques can be used to produce clinically relevant osteochondral
      repair tissue.

PMID- 18085206
TI  - Synthetic hydrogel matrices for guided bladder tissue regeneration.
AB  - Tissue engineering aims to provide a temporary scaffold for repair at the site of
      injury or disease that is able to support cell attachment and growth while
      synthesis of matrix proteins and reorganization take place. Although relatively
      successful, bladder tissue engineering suffers from the formation of scar tissue
      at the scaffold implant site partly due to the phenotypic switch of smooth muscle
      cells (SMCs) from a quiescent contractile phenotype to a synthetic proliferative
      phenotype, known as myofibroblast. We hypothesize that culturing human SMCs in
      enzymatically degradable poly(ethylene) glycol (PEG) hydrogels modified with
      integrin-binding peptides, and in co-culture with human urothelial cells (UCs),
      will offer some insight as to the required environment for their subsequent
      differentiation into quiescent SMCs. We have established protocols for isolation,
      culture, and characterization of human bladder UCs, SMCs, and fibroblasts and
      investigated co-culture conditions for SMCs and UCs. The optimal PEG hydrogel
      properties, promoting growth of these cells, have been investigated by varying
      the amounts of cell adhesion peptide, PEG, and crosslinker and examined using
      light and fluorescence microscopy. Furthermore, the cell organization within and
      on top of gels 14 days post seeding has been examined by histology and
      immunohistochemistry. We have investigated a co-culture model for UCs and SMCs
      integrated into PEG hydrogels, mimicking a section of the bladder wall for
      reconstructive purposes that also could contribute to the understanding of the
      underlying basic mechanisms of SMC differentiation.

PMID- 18085207
TI  - Generation of multicellular tumor spheroids by the hanging-drop method.
AB  - Owing to their in vivo-like characteristics, three-dimensional (3D) multicellular
      tumor spheroid (MCTS) cultures are gaining increasing popularity as an in vitro
      model of tumors. A straightforward and simple approach to the cultivation of
      these MCTS is the hanging-drop method. Cells are suspended in droplets of medium,
      where they develop into coherent 3D aggregates and are readily accessed for
      analysis. In addition to being simple, the method eliminates surface interactions
      with an underlying substratum (e.g., polystyrene plastic or agarose), requires
      only a low number of starting cells, and is highly reproducible. This method has
      also been applied to the co-cultivation of mixed cell populations, including the
      co-cultivation of endothelial cells and tumor cells as a model of early tumor
      angiogenesis.

PMID- 18085208
TI  - In vitro vascularization of human connective microtissues.
AB  - Vascularization is one of the most central processes enabling multicellular life.
      Owing to the complexity of vascularization regulatory networks, minor control
      imbalances often have severe pathologic consequences ranging from ischemic
      diseases to cancer. Tissue engineers are immediately confronted with
      vascularization as artificial tissues of a clinically relevant size require a
      vascular system to ensure vital physiologic logistics throughout the entire
      tissue and to enable rapid connection to the host vasculature following
      implantation. Using human umbilical vein endothelial cells (HUVECs) coated onto a
      human aortic fibroblast (HAF) core microtissue generated by gravity-enforced self
      assembly in hanging drops, we created a tissue-culture system for studying
      capillary network formation. We provide comprehensive technical insight into the
      design and analysis of prototype vascularization in multicell-type-based
      microtissues. Detailed understanding of generic processes managing capillary
      formation in human tissue culture may foster advances in the development of
      clinical tissue implants.

PMID- 18085209
TI  - Artificial skin.
AB  - Replacement of skin has been one of the most challenging aims for surgeons ever
      since the introduction of skin grafts in 1871. It took more than one century
      until the breakthrough of Rheinwald and Green in 1975 that opened new
      possibilities of skin replacement. The combination of cell culture and polymer
      chemistry finally led to the field of tissue engineering. Many researchers all
      over the world have been fascinated by the chance of creating a skin-like
      substitute ex vivo without any further harm to the patients, especially those
      with massive burns. Many different approaches to create new substitutes and
      further improvements in genetical and stem cell research led to today's skin
      equivalents. But still, the "gold standard" for wound coverage is the autologous
      split-thickness skin graft. Future research will aim at originating biologically
      and physiologically equal skin substitutes for the treatment of severe burns and
      chronic ulcers.

PMID- 18085210
TI  - Small blood vessel engineering.
AB  - Tissue engineering has attracted wide interest as a potential method to alleviate
      the shortage of transplantable organs (1). To date, almost all of the
      successfully engineered tissues/organs have relatively thin and/or avascular
      structures [e.g., skin (2), cartilage (3), and bladder (4)], where
      postimplantation vascularization from the host (angiogenesis) is sufficient to
      meet the implant's demand for oxygen and nutrients. Vascularization remains a
      critical obstacle impeding attempts to engineer thicker, metabolically demanding
      organs, such as heart and liver. One approach in vascularizing an engineered
      tissue is to add the cellular components of blood vessels (endothelial and
      perivascular cells) directly to the tissue-engineered construct. We have shown
      that coimplanting endothelial cells and perivascular cells in a scaffold in vivo
      can lead to the formation of a vascular network that anastomoses to the host
      circulatory system. The engineered vessels are stable and functional, and they
      persist for more than 1 year in vivo. This approach may potentially lead to the
      creation of a well-vascularized-engineered tissue.

PMID- 18085211
TI  - Artificial pancreas to treat type 1 diabetes mellitus.
AB  - Substitution of diseased organ/tissues with totally artificial machines or
      transplantable biohybrid devices where functionally competent cells are enveloped
      within immunoprotective artificial membranes could represent one of the future
      goals in medicine. In particular, artificial or, closer to feasibility, biohybrid
      artificial pancreas (BHAP) could replace the function of pancreatic islet beta
      cells that have been destroyed by autoimmunity, thereby obviating the need to
      treat patients with type 1 diabetes mellitus (TIDM) with multiple daily insulin
      injections. State-of-the-art diabetes therapy and perspectives in the use of
      BHAP, with special regard to islet-cell-containing microcapsules fabricated with
      alginate-based polymers, including applications to experimental animal models
      according to different chemical procedures, are reviewed. Special emphasis has
      been given to preparation methods, immunoprotection strategies, and
      biocompatibility of the islet-cell-containing microbarriers, as well as to
      approaches to ameliorate these features. Currently available BHAP prototypes have
      been critically reviewed to define expectations about the next generation devices
      targeting the final cure of TIDM.

PMID- 18085212
TI  - Human articular chondrocytes culture.
AB  - In this chapter, we describe a strategy to expand adult human articular
      chondrocytes in monolayer while maintaining high post-expansion chondrogenic
      capacity. This method relies on the use of a specific growth factor cocktail
      during the two-dimensional (2D) propagation of chondrocytes. In addition, a
      protocol to isolate and grow single-colony-derived strains of chondrocytes is
      presented as a model to study the biology of different chondrocyte
      subpopulations.

PMID- 18085213
TI  - Cardiomyocytes from human and mouse embryonic stem cells.
AB  - Human and mouse embryonic stem (ES) cells have the potential to differentiate to
      cardiomyocytes in culture. They are therefore of interest for studying early
      human and mouse heart development, as well as properties of cardiomyocytes from
      both species, including their responses to cardiac drugs, and, at some point in
      the future, may represent a source of transplantable cells for cardiac muscle
      repair. The differentiation protocols that are effective depend in part on the
      species from which the ES cell lines were derived, and in part on the individual
      cell lines and the methods used for their propagation prior to differentiation.
      Here, several methods for generating and characterizing cardiomyocytes from mouse
      and human ES cells are described, as well as methods for dissociation of
      cardiomyocytes into single-cell suspensions which are useful both for
      characterizing cells by antibody staining and electrophysiological measurements,
      as well as preparing cells for transplantation into (animal) hearts.

PMID- 18085214
TI  - Myocardial restoration and tissue engineering of heart structures.
AB  - The restoration or de novo engineering of heart structures poses a challenge
      because of the unique structure and physical properties of the heart. The heart
      is a heterogeneous, complex helical structure with asymmetric and anisotropic
      features. Hence, it is variably built and consists of spiraling muscle bands
      (first described by Torrent-Guasp), valves, coronary vessels, and a conduction
      system. Therefore, successful construction of muscular or valvular grafts needs
      to meet specific prerequisites, such as mechanical stability, optimal porosity,
      and contractile function. A series of studies have reported on various mixtures
      of scaffolds and (stem) cells and subsequent production of spontaneously
      contractile cardiac grafts in vitro. In vivo studies have provided evidence of
      engraftment of such bioartificial myocardial grafts and of improved heart
      function of the host. Two fundamental types of bioartificial/engineered valves
      have been reported: decellularized xenogeneic valves and recellularized valves
      with the recipient's own cells. Large-scale clinical results are awaited.
      Finally, bioartificial vessels are being produced, either through de novo
      construction from collagens and cells or from previously harvested recipient's
      own fibroblasts and endothelial cells. The main goal envisioned here is long-term
      patency following implantation in vivo. This review surveys upon recent
      developments and indicates caveats in the field of tissue engineering of cardiac,
      valvular, and vascular structures.

PMID- 18085215
TI  - Practical aspects of cardiac tissue engineering with electrical stimulation.
AB  - Heart disease is a leading cause of death in western society. Despite the success
      of heart transplantation, a chronic shortage of donor organs, along with the
      associated immunological complications of this approach, demands that alternative
      treatments be found. One such option is to repair, rather than replace, the heart
      with engineered cardiac tissue. Multiple studies have shown that to attain
      functional tissue, assembly signaling cues must be recapitulated in vitro. In
      their native environment, cardiomyocytes are directed to beat in synchrony by
      propagation of pacing current through the tissue. Recently, we have shown that
      electrical stimulation directs neonatal cardiomyocytes to assemble into native
      like tissue in vitro. This chapter provides detailed methods we have employed in
      taking this "biomimetic" approach. After an initial discussion on how electric
      field stimulation can influence cell behavior, we examine the practical aspects
      of cardiac tissue engineering with electrical stimulation, such as electrode
      selection and cell seeding protocols, and conclude with what we feel are the
      remaining challenges to be overcome.

PMID- 18085216
TI  - Biological scaffolds for heart valve tissue engineering.
AB  - Tissue engineering might bear promising solutions for overcoming the limitations
      of biological and mechanical heart valve substitutes. The concept of heart valve
      tissue engineering bases on decellularized biological matrices, as removal of
      cellular components might reduce immunological reactions, which are thought to be
      responsible for accelerated valvular graft deterioration and their subsequent
      repopulation with autologous cells, which leads to tissue integrity and
      continuous remodeling. Here, we report a method for efficient removal of cells
      from ovine heart valve tissue (including cusp, wall, and myocardial cuff) by
      detergents for the generation of biological valvular scaffolds.

PMID- 18085217
TI  - In vitro heart valve tissue engineering.
AB  - Heart valve replacement represents the most common surgical therapy for end-stage
      valvular heart diseases. A major drawback all contemporary heart valve
      replacements have in common is the lack of growth, repair, and remodeling
      capabilities. To overcome these limitations, the emerging field of tissue
      engineering is focusing on the in vitro generation of functional, living heart
      valve replacements. The basic approach uses starter matrices of either
      decellularized xenogeneic or biopolymeric materials configured in the shape of
      the heart valve and subsequent cell seeding. Moreover, in vitro strategies using
      mechanical loading in bioreactor systems have been developed to improve tissue
      maturation. This chapter gives a short overview of the current concepts and
      provides detailed methods for in vitro heart valve tissue engineering.

PMID- 18085218
TI  - Microtubules: an overview.
AB  - Microtubules are found in all eukaryotes and are built from alphabeta-tubulin
      heterodimers. The alpha-tubulins and beta-tubulins are among the most highly
      conserved eukaryotic proteins. Other members of the tubulin family have come to
      light recently and, like gamma-tubulin, appear to play roles in microtubule
      nucleation and assembly. Microtubule assembly is accompanied by hydrolysis of GTP
      associated with beta-tubulin so that microtubules consist principally of "GDP
      tubulin" stabilized by a short "GTP cap." Microtubules are polar, cylindrical
      structures some 25 nm in diameter. Protofilaments made from tubulin heterodimers
      run lengthwise along the microtubule wall with the beta-tubulin subunit at the
      microtubule plus end. The crystallographic structures of tubulins are essential
      to understand in detail microtubule architecture and interactions with
      stabilizing and destabilizing drugs and proteins.

PMID- 18085219
TI  - Large scale purification of brain tubulin with the modified Weisenberg procedure.
AB  - This method is a modification of the initial procedure employed to purify tubulin
      from mammalian brain. It consists of tissue homogenization, elimination of cell
      membranes, ammonium sulfate fractionation, and batch anion exchange, followed by
      selective precipitation with magnesium chloride. Half gram of electrophoretically
      homogenous, active, concentrated calf brain tubulin is typically purified in 9 h,
      dialyzed overnight, and stored under liquid nitrogen. Prior to use the protein is
      equilibrated in the experimental buffer and its concentration measured. This
      tubulin preparation has been very extensively characterized. Frozen aliquots have
      been found to retain microtubule assembly activity after 10 yr of storage.

PMID- 18085220
TI  - Purification and mass spectrometry identification of microtubule-binding proteins
      from Xenopus egg extracts.
AB  - Microtubule-binding proteins are conveniently divided into two large groups: MAPs
      (microtubule-associated proteins), which can stabilize, anchor, and/or nucleate
      microtubules, and motors, which use the energy of ATP hydrolysis for a variety of
      functions, including microtubule network organization and cargo transportation
      along microtubules. Here, we describe the use of Taxol-stabilized microtubules
      for purification of MAPs, motors, and their complexes from Xenopus egg extracts.
      Isolated proteins are analysed using sodium dodecyl sulfate gel electrophoresis
      and identified by various mass spectrometry and database mining technologies.
      Found proteins can be grouped into three classes: (1) known MAPs and motors; (2)
      proteins previously reported as associated with the microtubule cytoskeleton, but
      without a clearly defined cytoskeletal function; (3) proteins not yet described
      as having microtubule localization. Sequence-similarity methods employed for
      protein identification allow efficient identification of MAPs and motors from
      species with yet unsequenced genomes.

PMID- 18085221
TI  - Preparation and characterization of posttranslationally modified tubulins from
      Artemia franciscana.
AB  - Tubulin heterogeneity within eukaryotic cells is generated by differential gene
      expression and posttranslational modification of alpha- and beta-tubulin gene
      products, either as heterodimers or when polymerized into microtubules. The
      characterization of posttranslationally modified tubulins from the crustacean
      Artemia franciscana is presented, although tubulins from other sources can be
      studied with these procedures. Tubulin is prepared from cell free extracts by
      taxol-induced assembly and centrifugation of microtubules through sucrose
      cushions, which also yields microtubule-associated proteins, or it is purified to
      apparent homogeneity by relatively simple chromatographic procedures and
      assembly/disassembly steps. To detect posttranslationally modified tubulins
      protein samples are electrophoresed in sodium dodecyl sulfate (SDS)
      polyacrylamide gels, blotted to nitrocellulose membranes and probed with isoform
      specific antibodies. Isotubulins, for which gene-encoded amino acid differences
      and posttranslational modifications generate charge variations, are resolved in
      two-dimensional gels using isoelectric focusing followed by SDS polyacrylamide
      gel electrophoresis, a procedure useful for resolution of microtubule-associated
      proteins. Isoforms patterns are visualized by Coomassie blue and/or silver
      staining and individual isoforms are identified by antibody reactivity on Western
      blots. Tubulin isoforms are localized in Artemia by immunofluorescent staining of
      larvae. The focus of this chapter is the purification of tubulin from a nonneural
      source and characterization of tyrosinated, detyrosinated, and nontyrosinatable
      alpha-tubulins using polyclonal antibodies made to carboxy-terminal peptides of
      each isoform.

PMID- 18085222
TI  - Studying the structure of microtubules by electron microscopy.
AB  - Although the structures of individual proteins and moderately sized complexes of
      proteins may be investigated by X-ray crystallography, the interaction between a
      long polymer, such as a microtubule, and other protein molecules, such as the
      motor domain of kinesin, need to be studied by electron microscopy. We have used
      electron cryo-microscopy and image analysis to study the structures of
      microtubules with and without bound kinesin motor domains and the changes that
      take place when the motor domains are in different nucleotide states. Among the
      microtubules that assemble from pure tubulin, we select a minor subpopulation
      that has perfect helical symmetry, which are the best for three-dimensional
      reconstruction. Gold labeling can be used to mark the positions of certain
      regions of protein sequence.

PMID- 18085223
TI  - Fluorescence microscopy of microtubules in cultured cells.
AB  - Cytoplasmic microtubules are noncovalent polymers of the protein tubulin. In the
      cells, the main function of microtubules is to provide tracks for organelle
      transport. Two experimental approaches based on fluorescence microscopy are
      commonly used to examine organization of microtubules in mammalian tissue culture
      cells. The first experimental approach involves indirect immunofluorescence
      staining of chemically fixed cells with tubulin antibody. Fluorescence microscopy
      of immunostained specimens allows the examination of the distribution of
      microtubules in the cytoplasm at the moment of fixation. The second experimental
      approach involves introduction of tubulin subunits covalently labeled with a
      fluorochrome into the cytoplasm of living cells. Time-lapse fluorescence
      microscopy of cells containing labeled tubulin subunits allows to examine changes
      in the spatial organization of microtubules in the cytoplasm and also to directly
      observe their behavior. In this chapter, we describe preparation of samples for
      fluorescence microscopy of microtubules.

PMID- 18085224
TI  - Measurements of stathmin-tubulin interaction in solution.
AB  - Stathmin is an important phosphorylation-controlled regulator of microtubule
      dynamics and plays a crucial role in cell division and cell proliferation. In its
      non-phosphorylated form, stathmin is the protein that interacts the most tightly
      with tubulin, in a 2:1 tubulin-stathmin (T2S) complex that does not participate
      in microtubule assembly. The importance of stathmin at different levels of
      phosphorylation in different steps of mitosis This article is a short overview of
      the different methods that have been or could be used to monitor the kinetic and
      thermodynamic parameters of tubulin-stathmin interaction and to evaluate the
      effects of phosphorylation. The author has tried to emphasize how hydrodynamic
      and spectroscopic methods measuring direct binding of stathmin to tubulin can be
      complemented by methods that make use of linked functions, measuring how the
      change in a functional property of tubulin upon binding stathmin provides
      information on binding parameters.

PMID- 18085225
TI  - Analysis of microtubule dynamics by polarized light.
AB  - In this article, the author describes the needed instrumentation and the methods
      to be followed for the observation and measurement of the birefringence of single
      and bundled microtubules and of their ordered arrays using a polarizing
      microscope. As instruments, the traditional polarizing microscope and the
      recently developed LC-PolScope are discussed. As methods, we describe qualitative
      and quantitative observations, including notes on specimen preparations, which
      optimize the sensitivity and accuracy of measuring specimen retardance.

PMID- 18085226
TI  - Visualization of spindle behavior using confocal microscopy.
AB  - Numerous comparisons have shown that confocal imaging of fluorescently labeled
      samples has superior image clarity compared to traditional epifluorescence
      microscopy, especially when imaging through thick specimens. Nevertheless, one
      limitation of confocal microscopy is the speed at which these systems acquire
      images. Newer confocal technologies, however, have overcome this drawback by
      rapidly scanning images while still maintaining the precision and resolution of a
      confocal microscope. One example is the spinning disk confocal, which can rapidly
      acquire images with minimal photobleaching. The following protocol provides
      methodology using spinning disk technology to visualize spindle microtubule
      behavior in live breast cancer cells expressing green fluorescent protein:alpha
      tubulin. It begins with sample preparation, covers equipment setup and image
      acquisition, and ends with image processing and archiving. Image acquisition is
      subdivided into two categories- imaging the complete mitotic cycle and imaging
      rapid mitotic events, to address the varying parameters required for the each
      experiment.

PMID- 18085227
TI  - Live cell approaches for studying kinetochore-microtubule interactions in
      Drosophila.
AB  - Kinetochores are essential for the proper positioning, movement and segregation
      of chromosomes on spindle microtubules. Live cell analyses of kinetochore
      movements on the spindle provide an important tool for dissecting the molecular
      machinery underlying kinetochore-based chromosome motility. Here, we describe
      contemporary techniques for studying and manipulating kinetochore function in
      live Drosophila syncytial blastoderm-stage embryos and S2 cells.

PMID- 18085228
TI  - Analysis of tubulin transport in nerve processes.
AB  - In neurons, the molecular machinery for axonal growth and navigation is localized
      to the growth cone region, whereas tubulin is synthesized primarily in the cell
      body. Because diffusion serves as an efficient transport mechanism only for very
      short distances, tubulin has to be actively transported from the cell body down
      the axon. Two mechanistically distinct models for tubulin transport have been
      proposed. "Polymer model" postulates that tubulin moves in the form of
      microtubules preassembled in the cell body, whereas "subunit model" assumes that
      axonal microtubules are stationary, and that tubulin is delivered from the cell
      body in unassembled form. We used three independent quantitative approaches
      (photobleaching, fluorescence speckle microscopy, and microtubule plus end
      tracking) to demonstrate that axonal microtubules are stationary in rapidly
      growing axons produced by Xenopus spinal cord neurons in culture. These
      experiments strongly support subunit model for tubulin delivery.

PMID- 18085229
TI  - Analysis of microtubule-mediated intracellular viral transport.
AB  - Host microtubules and motor proteins are crucial to the intracellular transport
      of a number of viruses. Disruption of microtubules or suppression of motor
      functions can remarkably inhibit the movement of viruses in host cells. It is now
      known that incoming viruses use motor proteins to travel along microtubules from
      the plasma membrane to the nuclear or perinuclear replication site, whereas
      progeny viruses depend on microtubules and motors to move from the assembly site
      to the cell periphery. Here, we describe several major methods for analyzing
      microtubule-mediated intracellular viral transport, using adenovirus as an
      example.

PMID- 18085230
TI  - Xenopus oocyte wound healing as a model system for analysis of microtubule-actin
      interactions.
AB  - Microtubule-actin interactions are fundamental to many cellular processes such as
      cytokinesis and cellular locomotion. Investigating the mechanism of microtubule
      actin interactions is the key to understand the cellular morphogenesis and
      related pathological processes. The abundance and highly dynamic nature of
      microtubules and F-actin raise a serious challenge when trying to distinguish
      between the real and fortuitous interactions within a cell. Xenopus oocyte wound
      model represents an ideal system to study microtubule-actin interactions as well
      as microtubule-dependent control of the actin polymerization. Here, we describe a
      series of cytoskeleton specific treatments in Xenopus oocyte wound healing
      experiments and use confocal fluorescence microscopy to analyze fixed oocytes to
      examine microtubule-actin interactions.

PMID- 18085232
TI  - Clinical pharmacology and use of microtubule-targeting agents in cancer therapy.
AB  - The microtubule-targeting agents have made significant contributions to cancer
      therapy over the past 50 years. The vinca alkaloids and taxanes have been used to
      treat a broad range of malignancies, including leukemias and lymphomas and many
      types of solid tumors. The taxanes have been frequently used in the treatment of
      advanced ovarian, breast, lung, head and neck, and prostate cancer, and they are
      increasingly being used in early stage disease. This chapter reviews the
      pharmacology, clinical indications, and toxicities associated with the vinca
      alkaloids and taxanes.

PMID- 18085231
TI  - Screening for inhibitors of microtubule-associated motor proteins.
AB  - The mitotic spindle is an important target for cancer chemotherapy. The main
      protein target for drugs in clinical use is tubulin, the building block of
      microtubules. In recent years, other proteins of the mitotic spindle have been
      identified as potential targets for the development of more specific drugs with
      the hope that these will have fewer side effects than known antimitotics
      (taxanes, vinca alkaloids). The human genome contains more than 40 members of the
      kinesin superfamily, with at least 12 of these involved in mitosis and
      cytokinesis. HsEg5 (also called KSP, kinesin spindle protein), a member of the
      kinesin-5 family, involved in the formation of the bipolar spindle, is a very
      promising target for cancer chemotherapy with specific inhibitors in Phase I and
      II clinical trails. Several successful approaches exist today to screen Eg5 for
      inhibitors, including phenotype-based assays and simple in vitro assays that
      explore the intrinsic enzymatic ATPase activity of Eg5. Here, we describe a
      robust and straightforward in vitro method to rapidly screen Eg5 for inhibitors.
      The assay can easily be adapted to other mitotic kinesins that may be identified
      in the future as potential drug targets, or simply to obtain specific kinesin
      inhibitors for use in "chemical genetics" to study the function of this important
      class of proteins.

PMID- 18085234
TI  - Characterizing ligand-microtubule binding by competition methods.
AB  - The knowledge of the thermodynamics and kinetics of drug-microtubule interaction
      is essential to understand the structure/affinity relationship of a given ligand
      family. When a ligand does not show an appropriate signal change (absorbance or
      fluorescence) upon binding, the extensive direct characterization of its binding
      affinities and kinetic rate constants of association and dissociation becomes a
      complex task. In those cases it is possible to obtain these parameters by
      competition of the ligand with a reference one of the same binding site that
      shows such change. Nevertheless, although the experimental setup of the
      competition measurements is easier, the treatment of the data is complex because
      simultaneous equilibrium/kinetic equations have to be solved. In this chapter,
      the taxoid-binding site of the microtubules will be used as an example to
      describe experimental competition and data analysis methods to determine the
      binding constants and kinetic rates of association and dissociation of ligands
      for microtubules.

PMID- 18085233
TI  - Studying drug-tubulin interactions by X-ray crystallography.
AB  - Tubulin, the microtubule building-block, is the target of numerous small molecule
      compounds that interfere with microtubule dynamics. Several of these ligands are
      in clinical use as antitumor drugs. There have been numerous studies on these
      molecules, with two main objectives: to determine their mechanism of action and
      to find new compounds that would expand the arsenal available for cancer
      chemotherapy. Although these studies would undoubtedly benefit from structural
      data on tubulin, this protein has long resisted crystallization attempts. We have
      used stathmin-like domains (SLDs) of stathmin family proteins as a tool to
      crystallize tubulin and have obtained three-dimensional crystals of the
      tubulin:SLD complexes. As many tubulin ligands bind to these complexes, the
      crystals are valuable tools to study tubulin-drug interactions by X-ray
      crystallography. They open the way to a structure-based drug design approach.

PMID- 18085235
TI  - Methods for studying vinca alkaloid interactions with tubulin.
AB  - Vinca alkaloids play a vital role in chemotherapy protocols for a wide range of
      hematological and solid tumors. Studies of drug interactions with the drug
      target, tubulin or microtubules, have helped us to understand the cytotoxic and
      toxic effects. We present here in vivo and in vitro methods for studying vinca
      alkaloid interactions with tubulin. In vivo methods for examining drug effects on
      cell proliferation and intracellular tubulin or microtubules and direct
      visualization of drug effects by fluorescence microscopy are presented. In vitro
      methods for measuring drug affinity for tubulin by analytical
      ultracentrifugation, kinetics of drug binding by light scattering and drug
      effects on microtubules by turbidity are also presented.

PMID- 18085236
TI  - High-throughput screening of microtubule-interacting drugs.
AB  - Drugs that affect microtubule dynamics are among the most effective anticancer
      agents in routine clinical use. The standard assay for antimicrotubule agents
      observes the ability of a particular substance to affect in vitro microtubule
      assembly. We have modified these procedures so that they can be performed in 96
      well plates using a standard fluorescence plate reader. Two different protocols
      are provided in this chapter. One of these protocols is for ligands that inhibit
      microtubule polymerization, such as colchicine and related molecules. The second
      is for ligands that promote in vitro microtubule assembly, such as Taxol.

PMID- 18085237
TI  - Strategies for the development of novel Taxol-like agents.
AB  - Taxol, the first microtubule stabilizer identified, is one of the most important
      new anticancer drugs to be brought to the clinic in the past 20 yr. The clinical
      success of TaxolTM led to the development of a second-generation taxane,
      docetaxel (Taxotere), and multiple third-generation taxane derivatives are under
      development. Non-taxane microtubule-stabilizers of diverse chemical structures,
      including the epothilones and discodermolide, show promising preclinical
      activities and several epothilones are progressing through clinical trials. One
      important advantage of the new stabilizers is their ability to circumvent drug
      resistance mechanisms. The clinical development of these new classes of agents
      suggests that microtubule stabilizers will continue to be important drugs for the
      treatment of cancer. This chapter provides a brief history of Taxol and the
      discovery and development status of other classes of microtubule stabilizers.
      Although all microtubule-stabilizers share similar mechanisms of action,
      interesting subtle differences among the stabilizers are being detected. This
      chapter also provides some strategies for identifying the differences among
      microtubule stabilizers that may help prioritize them for development and
      clinical use.

PMID- 18085238
TI  - History of measuring O2 and CO2 responses.
AB  - Quantitative analysis of the chemical interactions of CO2 and O2 on ventilation
      from early 20th century to the present start with the amazingly steep CO2
      response found by Haldane and his pupils, proceed through discovery of the prime
      role of the H+ ion and the discovery of carotid body chemoreception. The
      interaction of central and peripheral drives and changes with time and acute and
      chronic altitude exposure are still under investigation.

PMID- 18085239
TI  - J.S. Haldane and some of his contributions to physiology.
AB  - Although the Oxford Conferences began in 1978 as a result of the inspiration of
      Dan Cunningham and others at the University Laboratory of Physiology in Oxford,
      the roots of the meetings can be traced to John Scott Haldane (1860-1936) and his
      colleagues at the turn of the century. Indeed, the Laboratory (or its
      predecessor) has had an exemplary persistence (some might say an obsession) with
      the role of oxygen and, particularly, carbon dioxide in the control of breathing
      for over 100 years. An early key paper was that by Haldane and J.G. Priestley in
      1905, "The regulation of the lung ventilation," where careful measurements of the
      Pco2 in alveolar gas under a variety of conditions showed its critical role in
      control. But, Haldane was a man of very wide interests and enormous energy, and
      he made many other contributions, some of which are discussed here. On the one
      hand, he had an intense interest in very practical issues, for example, the
      dangers of mine gases and, on the other, he had a distinctly philosophical,
      vitalist bent which colored his views of physiology.

PMID- 18085240
TI  - Control of the exercise hyperpnea: the unanswered question.

PMID- 18085241
TI  - A peripheral oxygen sensor provides direct activation of an identified
      respiratory CPG neuron in Lymnaea.
AB  - The mechanisms by which peripheral, hypoxia-sensitive chemosensory cells modulate
      the output from the respiratory central pattern generator (CPG) remain largely
      unknown. In order to study this topic at a fundamental level, we have developed a
      simple invertebrate model system, Lymnaea stagnalis wherein we have identified
      peripheral chemoreceptor cells (PCRCs) that relay hypoxia-sensitive chemosensory
      information to a known respiratory CPG neuron, right pedal dorsal 1 (RPeD1).
      Significance of this chemosensory drive was confirmed via denervation of the
      peripheral sensory organ containing the PCRCs, and subsequent behavioral
      observation. This study provides evidence for direct synaptic connectivity
      between oxygen sensing PCRCs and a CPG neuron, and describes a unique model
      system appropriate for studying mechanisms of hypoxia-induced, respiratory
      plasticity from the level of an identified synapse to whole animal behavior.

PMID- 18085242
TI  - Environmental hyperoxia and development of carotid chemoafferent function.
AB  - Exposure to hyperoxia in the first few weeks of life causes life-long impairment
      of carotid chemoreceptor function in rats, e.g., depressed carotid sinus nerve
      (CSN) and phrenic nerve responses to acute hypoxia. We determined the maximal CSN
      responses of anesthetized adult rats to severe hypoxia (ventilation with 100% N2)
      or asphyxia (stopped ventilator) after 1, 2, and 4 weeks of postnatal hyperoxia
      (60% O2) (PNH). As with acute responses to hypoxic stimuli, we find that maximal
      CSN responses are significantly attenuated with severity of attenuation dependent
      on duration of PNH. We suggest that impaired carotid chemoafferent input produced
      by PNH could play a role in failure of arousal in severely hypoxic states
      occurring in infants and adults.

PMID- 18085243
TI  - HSP70 reduces chronic hypoxia-induced neural suppression via regulating
      expression of syntaxin.
AB  - Long-term exposure to modest hypoxia conditions may result in neural dysfunction;
      however, the involvement of presynaptic proteins has not been tested directly.
      Here, we reported that adult snails, Lymnaea stagnalis, developed a slow righting
      movement after placement in low O2 (approximately 5%) for 4 days. Semi
      quantitative Western blot analysis showed that hypoxia induced heat shock protein
      70 (HSP70) up-regulation and a reduction of syntaxin I. The inducible HSP70
      occurs within 6 hours preceding the down-regulation of syntaxin I, suggesting
      that HSP70 may be involved in regulation of syntaxin expression. Injecting
      directly double-stranded RNAs (dsRNA) into the center ganglia region, we found
      that dsRNA HSP70, not the scrambled RNA, prevented the hypoxia-induced HSP70
      expression, enhanced the hypoxia-dependent down-regulation of syntaxin I, and
      aggravated motor suppression. We thus provided the first evidence that early
      induction of HSP70 by chronic hypoxia is critical for maintaining expression
      levels of presynaptic proteins and neural function. These findings implicate a
      new molecular mechanism underlying chronic hypoxia-induced neurobehavioral
      adaptation and impairment.

PMID- 18085244
TI  - Effect of systemic administration of the nitric oxide synthase inhibitor L-NMMA
      on the human ventilatory response to hypoxia.

PMID- 18085245
TI  - Effects of volatile anesthetics on carotid body response to hypoxia in animals.
AB  - This study was a systematic review of the anesthetic effect on carotid body
      response to hypoxia. We undertook a systematic literature search (electronic plus
      manual) for full-paper articles in English that used methodologies enabling any
      anesthetic effect to be located to the carotid body. We found just 7 articles
      that met our inclusion criteria, incorporating 16 separate studies. Anesthetic
      (mean dose +/- SD 0.70 +/- 0.33 MAC) significantly depressed carotid body
      response by 24% (p = 0.041). There were no differences between individual agents
      (halothane, enflurane, isoflurane) and no influence of the use of neuromuscular
      blockade or of species (although the data were sufficiently sparse to interpret
      such sub-group analysis with caution).

PMID- 18085246
TI  - Mutation of the von Hippel-Lindau gene alters human cardiopulmonary physiology.
AB  - Intracellular responses to hypoxia are coordinated by the von Hippel-Lindau-
      hypoxia-inducible factor (VHL-HIF) transcriptional system. This study
      investigated the potential role of the VHL-HIF pathway in human systems-level
      physiology. Patients diagnosed with Chuvash polycythaemia, a rare disorder in
      which VHL signalling is specifically impaired, were studied during acute hypoxia
      and hypercapnia. Subjects breathed through a mouthpiece and ventilation was
      measured while pulmonary vascular tone was assessed echocardiographically. The
      patients were found to have elevated basal ventilation and pulmonary vascular
      tone, and ventilatory, pulmonary vasoconstrictive and heart rate responses to
      acute hypoxia were greatly increased, as were heart rate responses to
      hypercapnia. The patients also had abnormal pulmonary function on spirometry.
      This study's findings demonstrate that the VHL-HIF signalling pathway, which is
      so central to intracellular oxygen sensing, also regulates the organ systems upon
      which cellular oxygen delivery ultimately depends.

PMID- 18085247
TI  - Intravenous endothelin-1 and ventilatory sensitivity to hypoxia in humans.
AB  - The effects of intravenous endothelin-1 (ET-1) on the ventilatory response to
      hypoxia were studied in healthy humans. Nine volunteers were each exposed twice
      to 4 hr eucapnic hypoxia. They received a continuous infusion of ET-1 during the
      ET-1 protocol and an infusion of saline during the control protocol. Plasma ET-1
      levels and an index of ventilation were measured regularly. Hypoxia caused a rise
      in plasma ET-1 in the control protocol. Hypoxia also caused the index of
      ventilation to increase in both protocols, and this increase was greater in the
      ET-1 protocol than in the control protocol. These results are consistent with the
      hypothesis that ET-1 plays a role in controlling the ventilatory response to
      hypoxia in man.

PMID- 18085248
TI  - Key roles for AMP-activated protein kinase in the function of the carotid body?
AB  - The carotid bodies play a critical role in initiating compensatory ventilatory
      responses to hypoxia. However, the complete mechanism by which hypoxia excites
      the oxygen-sensing carotid body type 1 cells has not been fully defined. We have
      previously proposed that the enzyme adenosine monophosphate-activated protein
      kinase (AMPK) may couple hypoxic inhibition of mitochondrial oxidative
      phosphorylation to carotid body type I cell excitation (Evans, Mustard, Wyatt,
      Peers, Dipp, Kumar, Kinnear and Hardie 2005). Here we discuss evidence that AMPK
      is a key requirement for hypoxic chemotransduction by the carotid body. In
      addition, we postulate upon a role for AMPK in the plasticity observed in the
      carotid body during both chronic and chronic intermittent hypoxia.

PMID- 18085249
TI  - Stimulatory actions of pituitary adenylate cyclase-activating polypeptide (PACAP)
      in rat carotid glomus cells.
AB  - The carotid bodies are the major peripheral chemoreceptors that detect changes in
      arterial blood oxygen level. PACAP-deficient mice are prone to sudden neonatal
      death and have reduced respiratory response to hypoxia and hypercapnia. To
      investigate whether PACAP contributes to the chemotransduction in carotid body,
      we studied the action of PACAP on glomus cells isolated from rat carotid body. We
      found that PACAP triggered cytosolic [Ca2+] ([Ca2+]i) rise in glomus cells.
      Removal of extracellular Ca2+ reversibly inhibited the PACAP-mediated [Ca2+]i
      rise. Under voltage clamp conditions and in the presence of tetraethylammonium
      (TEA) and Cd2+, PACAP reduced the outward current evoked at positive potentials.
      We suggest that the inhibition of a TEA-insensitive current is a mechanism
      underlying the PACAP-mediated [Ca2+]i rise in glomus cells. The loss of the
      stimulatory action of PACAP in glomus cells may partly account for the reduction
      in chemoresponse in the PACAP-deficient mice.

PMID- 18085250
TI  - Post-hypoxic unstable breathing in the C57BL/6J mouse: effects of acetazolamide.
AB  - We examined whether acetazolamide (ACZ), a carbonic anhydrase inhibitor, would
      alter post-hypoxic ventilatory behavior and periodic breathing in the C57BL/6J
      (B6) mouse. Experiments were performed with unanaesthetized, awake adult male B6
      mice (n = 5, 2.5 months old, 21.3 +/- 1.5 g, mean +/- SD) and ventilatory
      behavior was measured using a flow through body plethysmography. Mice were given
      an intraperitoneal injection of either vehicle or ACZ (40 mg/kg) and one hour
      later exposed to 1 min of 8% O2-balance N2 (poikilocapnic hypoxia) or 12%-O2, 3%
      CO2-balance N2 (non-poikilocapnic hypoxia) followed by rapid reoxygenation (100%
      O2) of 5 minutes. One minute after reoxygenation, ACZ-treated animals exhibited
      post-hypoxic frequency decline (p < 0.05), a lower coefficient of variability for
      frequency (p < 0.001) and no tendency towards periodic breathing (p < 0.05), as
      compared to vehicle-treated animals. ACZ improves unstable breathing in the B6
      model of periodic breathing, despite producing post-hypoxic frequency decline.
      Our speculation is that periodic breathing occurs through pathways independent of
      the A5 pontine area.

PMID- 18085251
TI  - Catecholaminergic modulation of the respiratory rhythm generator in the isolated
      brainstem-spinal cord preparation from neonatal rat.

PMID- 18085253
TI  - Pre-Botzinger complex neurokinin-1 receptor expressing neurons in primary cell
      culture.
AB  - Phenotypic identification of pre-Botzinger complex (pre-BotC) neurons is vital to
      the delineation of endogenous cellular properties involved in respiratory rhythm
      generation and neuromodulation of breathing. A subpopulation of pre-BotC neurons
      endowed with intrinsic rhythmicity is proposed as the kernel for inspiratory
      rhythm generation in vitro. In this study, the pre-BotC "island" preparation was
      excised from medullary slices and reduced to its heterogeneous cellular
      constituents using primary cell culture techniques. Cultured neurons were labeled
      with tetramethylrhodamine conjugated to Substance P (TMR-SP) to identify
      individual NK-1R expressing neurons. Data from this study provide initial
      evidence that the pre-BotC neurons living in culture remain functionally capable
      of binding and internalizing the fluorescently-tagged ligand and TMR-SP tagging
      is a useful experimental tool that reliably identifies the NK-1R phenotype.

PMID- 18085252
TI  - What role do pacemakers play in the generation of respiratory rhythm?
AB  - The pacemaker hypothesis that specialized neurons with conditional oscillatory-
      bursting properties are obligatory for respiratory rhythm generation in vitro has
      gained widespread acceptance, despite lack of direct proof. Here we critique the
      pacemaker hypothesis and provide an alternative explanation for rhythmogenesis
      based on emergent network properties. Pacemaker neurons in the preBotC depend on
      either persistent Na+ current I(NaP) or Ca(2+)-activated nonspecific cationic
      current (I(CAN)). Activity in slice preparations and synaptically- isolated
      pacemaker neurons undergo similar frequency modulation by perturbations including
      hypoxia and changes in external K+. These data have been used to argue that
      pacemaker cells must be rhythmogenic, but may simply reflect the action of these
      perturbations on intrinsic membrane properties throughout the preBotC and does
      not constitute proof that pacemakers necessarily drive the rhythm with synaptic
      coupling in place. Likewise, bath-applied drugs, such as riluzole (RIL) and
      flufenamic acid (FFA), attenuate I(NaP) and I(CAN), respectively, throughout the
      slice. Thus, when these drugs stop the rhythm, a widespread depression of
      excitability is likely the underlying cause, not selective blockade of bursting
      pacemaker activity. We propose that rhythmogenesis is an emergent network
      property, wherein recurrent synaptic excitation initiates a positive feedback
      cycle among interneurons and that intrinsic currents like I(CAN) and I(NaP)
      promote inspiratory burst generation by augmenting synaptic excitation in the
      context of network activity. In this group-pacemaker framework, individual
      pacemaker neurons can be embedded but play the same role as every other network
      constituent.

PMID- 18085254
TI  - Belt-and-suspenders as a biological design principle.
AB  - Recent studies have shown both the pFRG and the preBotC are sufficient to
      generate respiratory rhythm, and are hypothesized to do so via distinct
      mechanisms (Onimaru and Homma 2003; Mellen, Janczewski, Bocchiaro and Feldman
      2003). The coexistence of mechanistically distinct, functionally matching
      networks (defined as degeneracy, Edelman and Gally 2001) is a ubiquitous feature
      of motor networks in both invertebrates (Selverston and Miller 1980) and
      vertebrates (DiDomenico, Nissanov and Eaton 1988). In almost all cases, a
      consensus exists about which subsystem is the "primary" rhythm generator, yet
      consistently, the effect of modulators on the isolated primary rhythm generator
      is qualitatively different than their effect on the more intact network (Ayali
      and Harris-Warrick 1999) and, in the intact animal, all rhythmogenic networks are
      active during motor pattern generation. Thus, at best, ascribing primacy to a
      particular network has weak support (since the other networks can produce
      qualitatively similar patterns; Prinz, Bucher and Marder 2004) and little
      explanatory power (since effects of modulatory inputs on the isolated "primary"
      rhythm generator do not persist in more intact networks). The ubiquity of
      degenerate networks for motor pattern generation suggests that a more useful
      question is why such an organization exists. We propose that degeneracy is
      ubiquitous because it reduces the phenotype's sensitivity to genetic mutation and
      environmental perturbation, and broadens the adaptiveness of motor patterns.

PMID- 18085255
TI  - Two modes of respiratory rhythm generation in the newborn rat brainstem-spinal
      cord preparation.
AB  - Two respiration-related rhythm generators, the pre-Botzinger complex inspiratory
      and the parafacial pre-inspiratory rhythm generators, have been identified in the
      medulla of rodents that produce intrinsic periodic bursts. Although both
      generators can be independently active under specific conditions, they interact
      as a coupled oscillator system to regulate the respiratory rhythm. Here, we
      summarize different mechanisms of modulation of the respiratory rhythm in the
      brainstem-spinal cord preparation of newborn rats and discuss factors determining
      rhythm generator dominance. We show two different modes of respiratory rhythm
      generation in the brainstem-spinal cord preparation that depends on the
      background stimulation level.

PMID- 18085256
TI  - Possible roles of the weakly inward rectifying k+ channel Kir4.1 (KCNJ10) in the
      pre-Botzinger complex.
AB  - Rhythmic activity of respiratory neurons is dependent on the clearance of
      neurotransmitter by astrocytes. Astrocytes should also be involved in the
      permanent and rapid clearance of extracellular ions. We analyzed the expression
      of the weakly inwardly rectifying K+ channel Kir4.1 (KCNJ10) in the respiratory
      network and studied the possible functions for neuronal activity in the pre
      Botzinger complex.

PMID- 18085257
TI  - Contribution of pacemaker neurons to respiratory rhythms generation in vitro.
AB  - Neurons with pacemaker properties have been described in several neural networks.
      Nonlinearity of their bursting activity might enable them to facilitate onset of
      excitatory states or to synchronize neuronal ensembles. However, whether such
      neurons are essential for generating a network activity pattern remains mostly
      unknown. For the mammalian respiratory network, located in the preBotzinger
      complex (PBC), two types of pacemaker neurons have been described. Bursting
      properties of one type of pacemakers rely on the riluzole-sensitive persistent
      sodium current, whereas bursting mechanisms of a second type are sensitive to
      Cd2+ and flufenamic acid, a calcium-dependent nonspecific cationic current
      blocker. The role of pacemakers in the generation of respiratory rhythms in vitro
      is state dependent. Under control conditions, the respiratory network generates
      fictive eupneic activity; this activity depends on both riluzole-sensitive and
      flufenamic acid-sensitive pacemakers. During hypoxia, fictive eupneic activity is
      supplanted by the neural correlate of gasping and only riluzole-sensitive
      pacemaker neurons appear to be necessary for this rhythm. Thus, at least two
      types of pacemaker bursting mechanisms are present in the PBC and underlie
      fictive eupnea, whereas only one burst mechanism seems to be critical for gasping
      generation in vitro.

PMID- 18085258
TI  - Emergent bursting in small networks of model conditional pacemakers in the pre
      Botzinger complex.
AB  - This paper summarizes some lessons learned from the computational study of
      bursting oscillations in small networks of model pre-Botzinger complex (pBC)
      neurons. Dynamical systems analysis explains the mechanisms through which
      synaptic coupling enhances the dynamic range of bursting and predicts the
      existence of multiple forms of busting and tonic spiking solutions. This analysis
      also demonstrates that intrinsically bursting cells are not required for network
      bursting and suggests possible roles for cells with different intrinsic behaviors
      in enhancing the robustness of bursting.

PMID- 18085259
TI  - Brain nuclei controlling the spinal respiratory motoneurons in the newborn mouse.
AB  - A retrograde and transneuronal infection with rabies virus was performed in mouse
      neonates to locate the central nervous structures involved in the motor command
      of the spinal respiratory motoneurons and to discriminate the location and
      hierarchical organization of the neurons in and between these infected central
      nervous structures.

PMID- 18085260
TI  - Superoxide dismutase-1 influences the timing and post-hypoxic stability of
      neonatal breathing.
AB  - Reactive oxygen species (ROS) likely play a role in the hypoxic ventilatory
      response. We determined whether hypoxic responses were influenced by alterations
      in cellular redox status induced by reductions in superoxide dismutase-1 (SOD-1)
      activity, a cytosolic anti-oxidant enzyme. Using whole-body, continuous-flow
      plethysmography, we compared ventilatory responses to moderate hypoxia (10%
      inspired O2) of Sod1+/+, +/- and -/- postnatal day 4 (P4) littermates. Sod1+/-
      neonates exhibited a consistently lower breathing frequency than their wild-type
      littermates, regardless of inspired O2 level. While SOD-1 deficiency had no
      effect on the magnitude of the ventilatory response during hypoxia, it did
      compromise stability of breathing in the post-hypoxic period. Our results suggest
      SOD-1 stimulates ventilation and helps stabilize breathing after a hypoxic
      perturbation.

PMID- 18085261
TI  - Neurodevelopmental abnormalities in the brainstem of prenatal mice lacking the
      Prader-Willi syndrome gene Necdin.

PMID- 18085262
TI  - Consequences of prenatal exposure to diazepam on the respiratory parameters,
      respiratory network activity and gene expression of alpha1 and alpha2 subunits of
      GABA(A) receptor in newborn rat.
AB  - Diazepam (DZP) enhances GABA action at GABA(A) receptor. Chronic prenatal
      administration of DZP delays the appearance of neonatal reflexes. We examined
      whether maternal intake of DZP might affect respiratory control system in newborn
      rats (0-3 day-old). This study was conducted on unrestrained animals and medulla
      spinal cord preparations. In addition, the level of expression of the genes
      encoding for the alpha1 and alpha2 subunits of the GABA(A) receptor was assessed
      by quantitative real-time RT-PCR. In rats exposed to DZP, the respiratory
      frequency was significantly lower and the tidal volume higher than in controls
      with no significant alteration of the minute ventilation. The recovery from
      moderate hypoxia was delayed compared to controls. The respiratory-like frequency
      of medullary spinal cord preparation from DZP-exposed neonates was higher than in
      the control group. Acute applications of DZP (1 microM) to these preparations
      increased respiratory-like frequency in both groups, but this facilitation was
      attenuated following prenatal DZP exposure. The present data indicate that
      prenatal exposure to DZP alters both eupneic breathing and the respiratory
      response to hypoxia. These effects might partly be ascribed to the down
      regulation of the expression of genes encoding GABA(A) receptor subunits. On the
      other hand, the effects of DZP exposure on reduced preparations suggested changes
      in the GABA(A) receptor efficiency and/or disruption of the normal development of
      the medullary respiratory network.

PMID- 18085263
TI  - Modulation of perinatal respiratory rhythm by GABA(A)--and glycine receptor
      mediated chloride conductances.

PMID- 18085264
TI  - Laryngeal stimulation by an acid solution in the pre-term lamb.
AB  - In a mature organism, the contact between various liquids and the laryngeal
      mucosa triggers lower airway protective responses (cough, swallowing, arousal).
      These laryngeal chemoreflexes (LCR) are essential for preventing aspiration. In
      contrast, previous studies showed that LCR are responsible for apnea and
      bradycardia in the neonatal mammal. Consequently, LCR, especially when triggered
      by acid gastrolaryngeal reflux, are deemed responsible for some apneas of
      prematurity and many life-threatening events of infancy and, probably, for some
      cases of sudden infant death syndrome. Recently, we have revisited LCR in full
      term lambs during quiet sleep. Our results showed that the LCR triggered by HCl
      (pH 2), mimicking the acid component of an acid gastro-oesophageal reflux, were
      consistently like the mature LCR reported in adult mammals, without significant
      apneas and bradycardias (St-Hilaire 2005). These results prompted us to question
      whether premature birth alters LCR. Results show that LCR triggered in pre-term
      lambs by both saline and HCl are much more marked and clinically relevant than
      the ones observed in full-term lambs. Indeed, life-threatening responses to HCl,
      including repetitive apneas for more than 90 seconds, severe desaturation and
      bradycardia, were observed in 2 lambs at postnatal day 7 (D7). In addition, LCR
      were significantly blunted at D14. In conclusion, HCl can trigger potentially
      dangerous LCR in pre-term lambs at D7, suggesting that LCR in response to acid
      gastrolaryngeal refluxes are likely involved in some
      apnea/bradycardia/desaturation in pre-term infants, before they reach a post
      conceptional age equivalent to full gestation.

PMID- 18085265
TI  - Necdin gene, respiratory disturbances and Prader-Willi syndrome.
AB  - Prader-Willi Syndrome (PWS) is a complex neurogenetic disease with various
      symptoms, including breathing deficits and possible alteration of serotonin (5HT)
      metabolism. As PWS results from the absence of paternal expression of several
      imprinted genes among which NECDIN (Ndn), we examined whether Ndn deficiency in
      mice induced breathing and 5HT deficits. In vivo, Ndn-deficient mice (Ndn-/-) had
      irregular breathing, severe apneas and blunted respiratory response to hypoxia.
      In vitro, medullary preparations from Ndn-/- neonates produced a respiratory-like
      rhythm that was highly irregular, frequently interrupted and abnormally regulated
      by central hypoxia. In wild type (wt) and Ndn-/- neonates,
      immunohistofluorescence and biochemistry revealed that medullary 5HT neurons
      expressed Ndn in wt and that the medulla contained abnormally high levels of 5HT
      in Ndn-/-. Thus, our preliminary results fully confirm a primary role of Ndn in
      PWS, revealing that Ndn-deficiency in mice induces respiratory and 5HT
      alterations reminiscent of PWS.

PMID- 18085266
TI  - Quantitative analysis of the oxygen transfer in the human acinus.
AB  - The gas transport in the acinus is limited at rest by the finite oxygen
      diffusivity. Although the simplest steady-state model of diffusion permits
      understanding a number of observations, it fails to quantitatively fit the value
      of the absolute flux of oxygen at rest and exercise. In this paper, we show that
      the binding of oxygen to hemoglobin modifies these values only slightly. In
      contrast, the dynamics of breathing have a strong effect and allow recovery to
      known experimental values for oxygen transfer.

PMID- 18085267
TI  - Role of diffusion screening in pulmonary diseases.
AB  - It has been shown recently that the acinus is only partially efficient in normal
      conditions. This is due to a "screening effect" governed by the relative values
      of the oxygen diffusivity and the membrane resistance as well as design and size
      of the acinus. These effects depend on the fraction of the acinus in which gas
      transport is governed by diffusion, then on the location of the convection
      diffusion transition. It is shown that these screening effects gives to
      respiration at rest a partial protection against several types of pulmonary
      diseases. This is true for mild emphysema, mild asthma or COPD and mild edema. In
      contrast, under exercise respiration, the acinus is totally efficient and the
      protective effects linked to the existence of screening do not exist anymore.

PMID- 18085268
TI  - A dp/dt method to assess dynamic properties of lung mechanoreceptors.
AB  - The activity of airway slowly adapting mechanoreceptors (SARs) reflects the
      presence of both a static and dynamic component. The dynamic response is
      typically assessed by the adaptation index; however, this is an indirect
      reflection of the more appropriate physiological stimulus, the rate of change of
      inflation pressure (dp/dt). We describe a method in which measurement of receptor
      discharge exceeding the SAR static response is used to measure dynamic discharge
      and dynamic sensitivity of lung mechanoreceptors. Repeat inflations with varying
      dp/dt illustrate the method for a SAR in which the dynamic sensitivity is
      inversely related to dp/dt and the initial "onset" discharge is highly dp/dt
      sensitive. The method may provide new insight into the classification and
      behaviour of lung mechanoreceptors.

PMID- 18085269
TI  - Pulmonary gas exchange in anatomically-based models of the lung.
AB  - Pulmonary gas exchange can be investigated at different scales of interest. Our
      approach is to couple models of gas exchange to anatomically-detailed models of
      the airway and pulmonary vascular trees. We are linking a hierarchy of models
      from the capillary segment up to the whole lung, so that a change in the detailed
      small-scale behaviour has a flow-on effect to function at a larger scale. The
      anatomically-based models will be used to understand how regional perturbations
      to the structure or function of the airway and vascular trees and the state of
      health of the functional tissue affect gas exchange. We are interested in the
      degree to which the system can be perturbed before it is detected by standard
      laboratory measures.

PMID- 18085270
TI  - Multi-scale models of the lung airways and vascular system.
AB  - Medical imaging now enables measurement of the lung in vivo at controlled
      volumes, prompting the development of increasingly sophisticated models of the
      geometry of the lung, from the largest airways and vessels to the alveolar tissue
      and capillary bed. We have developed methods for deriving subject-specific models
      of the airway and pulmonary vascular trees and have developed methods to
      represent the structure of alveolated parenchymal tissue and the segmented
      alveolocapillary network. These multi-scale models have geometry that is
      consistent with published lung morphometry and have defined relationships with
      one another. The models can therefore be readily exploited to couple multiple
      processes at the same physical scale (e.g., tissue mechanics and blood flow), or
      to couple over multiple scales (e.g., Newtonian flow in the large elastic blood
      vessels, and two-phase fluid transit in the microcirculation). We have studied
      function in the peripheral pulmonary system (alveolated airways and accompanying
      arterial and venous vessels) using a multi-scale approach that integrates
      detailed structure at this level of interest with estimates of air, blood and
      tissue pressures from functional models in the larger airways and vessels and
      simulations of soft tissue deformation of the whole lung. This approach allows us
      to study how ventilation of the acinus, mixing of inert gases and perfusion of
      the capillary bed varies with gravity, location in the lung and posture. An
      extension of the multi-scale models is incorporation of respiratory gas exchange,
      which can also be considered at several scales of interest.

PMID- 18085271
TI  - Modeling structure-function interdependence of pulmonary gas exchange.
AB  - Modeling functional processes, such as gas exchange, that occur deep in the lung
      far from where one can directly observe, depends on knowledge about the precise
      and quantitative design of the structure of the gas exchanger. This is the case
      as well for the actual arrangement of alveoli and blood capillaries at the gas
      exchange surface as for the disposition of gas exchange units with respect to the
      airway and vascular trees. The serial arrangement of alveoli and their perfusion
      as parallel units have important consequences for gas exchange.

PMID- 18085272
TI  - Ventilatory control during intermittent high-intensity exercise in humans.
AB  - Intermittent supra-maximal cycling of varying work: recovery durations was used
      to explore the kinetics of respiratory compensation for the metabolic acidosis of
      high-intensity exercise (> lactate threshold, thetaL). For a 10:20s duty-cycle,
      blood [lactate] ([L-]) was not increased, and there was no evidence of
      respiratory compensation (RC); i.e, no increase in the ventilation (VE)-CO2
      output (Vco2) slope, nor fall in end-tidal PCO2 (PETCO2). For longer duty-cycles,
      [L-] was elevated, stabilizing (30s:60 s exercise) or rising progressively
      (60s:120s, 90s: 180s exercise). In addition, Vco2 and VE now oscillated with WR,
      with evidence of delayed RC (progressive increase in VE - VCO2 slope; decrease in
      PETCO2) being more marked with longer duty-cycles. These results, which extend
      earlier findings with supra- thetaL step and ramp exercise, are not consistent
      with an appreciable contribution to RC from zero-order central command or
      peripheral neurogenesis. The reasons for the slow RC kinetics are unclear, but
      may reflect in part the H(+)-signal transduction properties of carotid
      chemoreceptors.

PMID- 18085273
TI  - Exercise-induced respiratory muscle work: effects on blood flow, fatigue and
      performance.

PMID- 18085274
TI  - Phase relations between rhythmical movements and breathing in wind instrument
      players.

PMID- 18085275
TI  - The effect of two different intermittent hypoxia protocols on ventilatory
      responses to hypoxia and carbon dioxide at rest.
AB  - Intermittent hypoxia (IH) consists of bouts of hypoxic exposure interspersed with
      normoxic intervals. The optimal IH regime for increasing the ventilatory response
      in humans is unknown, although in animals there is evidence that multiple short
      duration bouts of intermittent hypoxia (SDIH) provoke larger changes in
      chemosensitivity than longer duration bouts of intermittent hypoxia (LDIH). The
      purpose of this study was to compare responses to both hypercapnia and hypoxia
      between the two protocols. METHODS: In a randomised crossover design, 10 healthy
      males underwent two 7-day poikilocapnic IH protocols. The LDIH protocol consisted
      of daily 60-minute exposures to normobaric 12% O2 (balance N2). The SDIH protocol
      comprised twelve 5-minute bouts of normobaric 12% O2, separated by 5-minute bouts
      of room air daily. We measured the isocapnic acute hypoxic ventilatory response
      (HVR), hypercapnic ventilatory response (HCVR) and CO2 threshold and sensitivity
      by the modified Read rebreathing technique. Pre-testing was performed immediately
      prior to intermittent hypoxic training. Follow-up testing occurred on the first
      day following IH and at 7 days after completion of IH. HVR testing was also
      performed on every day of the IH protocol prior to the hypoxic exposure. RESULTS:
      Following each 7-day IH protocol, mean HVR was significantly (p < 0.05) increased
      by 67% and 49% (for LDIH and SDIH, respectively). One week post IH, HVR values
      were not different from pre-values. HCVR was increased significantly by the LDIH
      protocol by 44.1% (p < 0.01) and remained elevated by 41.5% at 7 days post (p <
      0.01). The changes following the SDIH protocol were smaller (20.7% and 13.5%, at
      1 and 7 days post IH, respectively) and not significant. The HCVR remained
      elevated 7 days following IH (26.7%, p < 0.01). In both the hyperoxic and hypoxic
      modified rebreathing tests, the CO2 sensitivity was unchanged by either
      intervention. In hypoxia, the CO2 threshold was significantly reduced following
      both protocols (p < 0.05). LDIH reduced the threshold by 1.60mmHg, whereas
      following SDIH it was reduced by 1.98mmHg. Under hyperoxic conditions, LDIH
      reduced the CO2 threshold by 2.06 mmHg, and SDIH caused a reduction of 2.53 mmHg.
      There were no significant differences between the two IH protocols for any of the
      above measures. A 7-day intermittent hypoxic protocol consisting of daily 60
      minute exposures to normobaric poikilocapnic hypoxia caused increases in HVR and
      HCVR. This protocol caused a left-shift in the CO2 threshold but no change in CO2
      sensitivity by the modified rebreathing protocol. Neither protocol proved
      superior in effecting these changes in the resting control of breathing.

PMID- 18085276
TI  - Respiratory long-term facilitation: too much or too little of a good thing?
AB  - Respiratory long-term facilitation (LTF), a prolonged augmentation of respiratory
      motor output, is induced by intermittent hypoxia in anesthetized or sleeping rats
      (and humans in limited conditions). Whether such augmentation in the controller
      response is of physiological benefit in terms of ventilatory stability remains
      uncertain; its impact on ventilatory stability will be determined to some extent
      by its effects on CO2 chemoreflex loop gain. We used integrated nerve responses
      in a rat model of LTF to assess chemoreflex parameters related to breathing
      stability. In this model, LTF decreases chemoreflex threshold but increases
      chemoreflex gain. Whereas a decreased chemoreflex threshold would promote
      ventilatory stability, increased chemoreflex gain represents a destabilizing
      influence. Based on these considerations alone, the impact of respiratory LTF on
      respiratory stability remains unclear.

PMID- 18085277
TI  - Contribution of endothelin-1 and endothelin A and B receptors to the enhanced
      carotid body chemosensory responses induced by chronic intermittent hypoxia.

PMID- 18085278
TI  - Intermittent hypoxia induces respiratory long-term facilitation in postnatal
      rats.

PMID- 18085279
TI  - Respiratory control, respiratory sensations and cycling endurance after
      respiratory muscle endurance training.
AB  - Respiratory muscle endurance training (RMET) was shown to increase endurance
      performance in healthy subjects. Reduced adverse respiratory sensations might
      contribute to this improvement. In the present study, we aimed to assess the
      relationship between changes in respiratory sensations and changes in ventilation
      and endurance performance after RMET. Fourteen healthy subjects completed either
      forty 15-min RMETs (n = 8) or did no training (control, n = 6). Respiratory
      endurance increased significantly after RMET while breathlessness and respiratory
      exertion were significantly reduced. Cycling endurance did not change while
      average ventilation was increased and perception of respiratory exertion was
      reduced. We conclude that (1) RMET reduces adverse respiratory sensations during
      isolated and exercise-induced hyperpnea even in the face of increased respiratory
      drive, and (2) the reduction in adverse respiratory sensations after RMET does
      not per se cause an increase in endurance performance. Whether the reduced
      perception of adverse respiratory sensations during exercise after RMET might be
      the cause of the increased respiratory drive remains to be clarified.

PMID- 18085280
TI  - Non-dimensional quantification of the interactions between hypoxia, hypercapnia
      and exercise on ventilation in humans.
AB  - The purpose of this study was to develop a non-dimensional approach towards the
      description of interaction between the three respiratory stimuli of hypoxia,
      hypercapnia and exercise and to use this approach to quantify the relative
      strengths of their interactions. Only a part of the study related to the overall
      interaction of the three stimuli is presented here. Nine volunteers took part in
      the study and their ventilatory responses to hypoxia were measured under four
      different conditions of rest-eucapnia, rest-hypercapnia, exercise-eucapnia and
      exercise-hypercapnia. Non-dimensional linear functions of hypercapnia (x),
      hypoxia (y) and exercise (z) were defined such that a value of one would double
      the resting ventilation. Non-dimensional ventilation v was derived as: v(x,y,z) =
      1+ x + y + z + g1xy + g2xz + g3yz + g4xyz, where g1, g2, g3 and g4 provide non
      dimensional measures of the strength of stimulus interaction. These interactions
      were calculated from the parameters obtained by fitting simple respiratory models
      to the data. The values for g1, g3 and g4 were significantly different from zero
      (p < 0.05, t-test). An intriguing result of this study is the overall negative
      interaction of the three stimuli, which may suggest that the linear, stimulus
      response models commonly used to describe respiratory data may not be adequate
      for describing these complex interactions.

PMID- 18085281
TI  - Elevated body temperature exaggerates laryngeal chemoreflex apnea in decerebrate
      piglets.
AB  - We investigated the interaction between body temperature and the duration of the
      laryngeal chemoreflex (LCR) in decerebrate piglets. Elevating body temperature by
      approximately 2 degrees C prolongs the duration of the LCR and the length of
      apnea associated with the reflex. This thermal prolongation seems to arise within
      the nucleus of the solitary tract in the brainstem, and we believe the thermal
      effect is mediated by enhanced GABAergic neurotransmission.

PMID- 18085282
TI  - Effects of systemic administration of mirtazapine on respiratory muscle activity
      in sleeping rats.
AB  - Mirtazapine (MIRT) is an antidepressant with mixed noradrenergic and serotonergic
      effects in central nervous system. The present study was undertaken to assess
      whether MIRT can stimulate genioglossus muscle (GG) activity in the conscious,
      behaving rat. Nine male rats were chronically instrumented with GG and neck
      muscle EMG electrodes. EEG electrodes were implanted to acquire sleep stage.
      Results demonstrated a dose-dependent effect of MIRT on GG activity during sleep,
      although no changes reached statistical significance. Low dose MIRT (0.1 mg/kg)
      showed a slight increase in GG phasic activity. In contrast, higher doses of MIRT
      (0.5-1.0 mg/kg) tended to decrease GG activity relative to vehicle, in addition
      to decreasing total sleep time.

PMID- 18085283
TI  - Control of genioglossus muscle by sleep state-dependent neuromodulators.
AB  - Pharyngeal muscle tone decreases in sleep and this predisposes some individuals
      to obstructive sleep apnea. This review summarizes the control of the
      genioglossus muscle by sleep-state dependent neuromodulators at the hypoglossal
      motor nucleus, the source of motor output to the genioglossus muscle of the
      tongue. Knowledge of such mechanisms is relevant to identifying and developing
      new strategies to augment pharyngeal muscle activity in sleep, potentially as
      treatments for obstructive sleep apnea.

PMID- 18085284
TI  - Significance of multiple neurochemicals that regulate respiration.
AB  - Current efforts to characterize the neuronal mechanisms that underlie automatic
      breathing generally adopt a 'minimalist' approach. In this review, we survey
      three of the many neurochemicals that are known to be present in raphe neurons
      and may be involved in respiration. Specifically, we ask the question, 'Is the
      minimalist approach consistent with the large number of neuronal types and
      neurochemicals found in respiratory centres'?

PMID- 18085285
TI  - Disinhibition of the dorsomedial hypothalamus increases the frequency of
      augmented breaths in the anesthetized rat.
AB  - The present study was undertaken to identify if activation of the dorsomedial
      hypothalamus (DMH) elicits augmented breaths (ABs). DMH disinhibition in urethane
      anesthetized rats produced both an increase in baseline respiratory rate (RR) and
      an increase in the number of ABs. The increase in RR was associated with a
      decrease in both the time of inspiration (T(i)) and expiration (T(e)) and the
      peak change in RR was observed 5 min post DMH activation. In contrast, the
      increase in ABs was greatest during the first 1.25 min, and both T(i)s of the ABs
      did not change significantly from pre-injection values. The T(e) of the ABs did
      decrease but remained significantly greater than the T(e) of the normal breath
      during DMH disinhibition. Our results support the hypothesis that the central
      neural pathway involved in the maintenance of normal respiratory pattern may be
      distinct from pathways involved in the generation of ABs.

PMID- 18085286
TI  - Major components of endogenous neurotransmission underlying the discharge
      activity of hypoglossal motoneurons in vivo.
AB  - Multibarrel micropipettes were used to simultaneously record unit activity and
      apply antagonists on individual inspiratory hypoglossal motoneurons (IHMNs) to
      determine the endogenous activation levels of NMDA, non-NMDA, GABA(A) and
      serotonin receptors responsible for the IHMN spontaneous discharge patterns in
      decerebrate dogs. IHMN activity is highly dependent on glutamatergic phasic and
      tonic drives, which are differentially mediated by the receptor subtypes.
      Endogenous serotonin significantly amplifies IHMN activity, while GABAergic gain
      modulation acts to attenuate activity. Thus, alterations in the neurotransmission
      of any of these systems could markedly alter neuronal output to target muscles.

PMID- 18085287
TI  - Control of ventilation in diving birds.
AB  - Studies on diving ducks indicate that the carotid bodies affect dive duration
      when the birds are hypoxic before a dive but not when they are hypercapnic. When
      close to their critical concentrations (beyond which the ducks will not dive),
      both oxygen and carbon dioxide reduce dive duration but hypercapnia has a much
      larger influence than hypoxia on surface duration. Also, excessive removal of
      carbon dioxide before a dive may be as important a factor in preparing for that
      dive as the replacement of the oxygen used during the previous dive. This
      observation is compatible with a physiological model of the control of diving
      behaviour in the Weddell seal which emphasises the significance of the level of
      carbon dioxide in the blood perfusing the brain.

PMID- 18085288
TI  - Evolutionary trends in respiratory mechanisms.
AB  - As we progress through the vertebrate phyla we see a number of changes in the
      functional morphology of the respiratory system that offer insights into the
      physiological systems that control them. We see a switch from a buccal pump
      powered by branchiomeric and hypobranchial muscles innervated by cranial nerves
      to a thoraco-abdominal aspiration pump powered by axial muscles innervated by
      spinal nerves with pre-motor neurons situated in the ventral respiratory column.
      The initial steps in the evolution of air breathing were a behavioural commitment
      to surface and changes in valving of the mouth/spiracle/nares and the operculum
      and glottis (or their equivalents) (i.e., changes in the activation of the
      muscles dilating and/or constricting various openings). These allowed the
      production of water breaths versus deflation or inflation of the air-breathing
      organ. Changes in the respiratory pump muscles evolved later. While highly
      speculative, it is suggested that these three independent valving circuits may
      have arisen in association with different pairs of segmental rhythm generators,
      and that all circuits continue to work together in a coordinated fashion to
      produce all types of breaths (including eupneic breaths and gasps).

PMID- 18085289
TI  - A computer model of mammalian central CO2 chemoreception.
AB  - We developed a single compartment model of a mammalian CO2 sensitive neuron and
      tested the hypothesis that pH-dependent inhibition of multiple potassium channels
      contributes to CO2 sensitivity. pH-dependent inhibition of potassium channels by
      either intracellular or extracellular pH was sufficient to alter neuronal
      activity, but changes in neither intracellular nor extracellular pH are required
      to elicit a neuronal response to hypercapnic stimulation.

PMID- 18085290
TI  - A mathematical model of pH(i) regulation in central CO2- chemoreception.
AB  - In CO2 chemosensitive neurons, an increase in CO2 (hypercapnia) leads to a
      maintained reduction in intracellular pH (pH(i)) while in non-chemosensitive
      neurons pH(i) recovery is observed. The precise mechanisms for the differential
      regulation of pH(i) recovery between these cell populations remain to be
      identified; however, studies have begun to explore the role of Na+/H+ exchange
      (NHE). Here, we compare the results of two different formulations of a
      mathematical model to begin to explore pH(i) regulation in central CO2
      chemoreception.

PMID- 18085291
TI  - Plasticity in the brain: influence of bilateral carotid body resection (bCBR) on
      central CO2 sensitivity.
AB  - We investigated the effect of bilateral carotid body resection (bCBR) in a
      patient with bilateral carotid body tumors on central CO2 sensitivity. We applied
      multiple square-wave changes in end-tidal CO2 and measured ventilation before the
      first surgery and at regular intervals for 3 years after surgery. The data were
      analyzed using a two-compartment model of the ventilatory control system. bCBR
      resulted in the loss of the fast response to CO2, and a sharp reduction in the
      magnitude of central CO2 sensitivity (a reduction of about 80% within 3 months
      after bCBR). Central CO2 sensitivity gradually increased to pre-operative values
      within 2 years after surgery. These observations are a strong indication for (1)
      the existence of a tonic influence from the peripheral chemoreceptors of the
      carotid bodies on central CO2 drive; (2) absence of any recovery of the
      peripheral drive after bCBR; and (3) neural plasticity causing the regeneration
      of central drive after bCBR.

PMID- 18085292
TI  - Glial modulation of CO2 chemosensory excitability in the retrotrapezoid nucleus
      of rodents.
AB  - We investigated the possibility that astrocytes modify the extracellular milieu
      and thereby modify the activity of central CO2 chemosensory neurons. The ability
      of astrocytes to modify the extracellular milieu is heterogeneously distributed
      among chemosensory sites that have, at least nominally, the same function. The
      differences in astrocytic activity may make some central chemosensory sites
      better attuned to the local brain tissue environment and other chemosensory sites
      better suited to integrate chemosensory activity from multiple sites within and
      outside the central nervous system.

PMID- 18085293
TI  - The carotid chemoreceptors are a major determinant of ventilatory CO2 sensitivity
      and of PaCO2 during eupneic breathing.
AB  - Both carotid and intracranial chemoreceptors are critical to a normal ventilatory
      CO2-H+ chemosensitivity. At low levels of hypercapnia, the carotid contribution
      is probably greater than the central contribution but, at high levels, the
      intracranial chemoreceptors are dominant. The carotid chemoreceptors are also
      critical to maintaining a stable and normal eupneic PaCO2, but lesion-induced
      attenuation of intracranial CO2-H+ chemosensitivity does not consistently alter
      eupneic PaCO2. A major unanswered question is why do intracranial chemoreceptors
      in carotid body denervation (CBD) animals tolerate an acidosis during eupnea
      which prior to CBD elicits a marked increase in breathing.

PMID- 18085294
TI  - The retrotrapezoid nucleus and central chemoreception.
AB  - Central respiratory chemoreception (CRC) is the mechanism by which brain pCO2
      regulates breathing. The molecular and cellular basis of CRC is still poorly
      understood. In this review, we describe the properties of a cluster of pH
      responsive neurons located in the retrotrapezoid region of the medulla oblongata
      and analyze whether these cells qualify as central respiratory chemoreceptors.

PMID- 18085295
TI  - The chemosensitive response of neurons from the locus coeruleus (LC) to
      hypercapnic acidosis with clamped intracellular pH.
AB  - Currently, a change in pH(i) is believed to be the major signal in the
      chemosensitive (CS) response of brainstem neurons to hypercapnia; however,
      multiple factors (e.g., Ca2+, CO2, pH(i), and pHo) have been suggested to
      contribute to this increase in firing rate. While there is evidence for a
      significant role of pH(i) in the CS response, we hypothesize that hypercapnic
      acidosis (HA) can increase firing rate even with no change in pH(i). We tested
      several methods to clamp pH(i), including high intracellular buffer and the use
      of rapid diffusion of weak bases or weak acids through the cell membrane. We were
      able to clamp pH(i) during hypercapnic exposure using weak acids. We observed a
      CS response to HA, with pH(i) clamped, indicating that intracellular
      acidification, while sufficient to increase firing rate, is not required for the
      response of CS neurons. The CS response to HA without a change in pH(i) is most
      likely due to extracellular acidification and/or increased CO2 and strongly
      supports the multiple factors model of chemosensitive signaling.

PMID- 18085296
TI  - CO2-sensitivity of GABAergic neurons in the ventral medullary surface of GAD67
      GFP knock-in neonatal mice.
AB  - We investigated the CO2 responsiveness of GABAergic neurons in the ventral
      medullary surface (VMS), a putative chemoreceptive area using a 67-kDa isoform of
      GABA-synthesizing enzyme (GAD67)-green fluorescence protein (GFP) knock-in
      neonatal mouse, in which GFP is specifically expressed in GABAergic neurons. The
      slice was prepared by transversely sectioning at the level of the rostral rootlet
      of the XII nerve and the rostral end of the inferior olive in mock cerebrospinal
      fluid (CSF). Each medullary slice was continuously superfused with hypocapnic
      CSF. GFP-positive neurons in the VMS were selected by using fluorescent optics
      and their membrane potentials and firing activities were analyzed with a
      perforated patch recording technique. Thereafter, superfusion was changed from
      hypocapnic to hypercapnic CSF. In 4 out of 8 GABAergic neurons in the VMS,
      perfusion with hypercapnic CSF induced more than a 20% decrease in the discharge
      frequency and hyperpolarized the neurons. The remaining 4 GFP-positive neurons
      were CO2-insensitive. GABAergic neurons in the VMS have chemosensitivity.
      Inhibition of chemosensitive GABAergic neural activity in the VMS may induce
      increases in respiratory output in response to hypercapnia.

PMID- 18085297
TI  - Multiple central chemoreceptor sites: cell types and function in vivo.
AB  - Central chemoreception is a distributed property involving many sites and
      neuronal types. Focal acidosis in conscious or anesthetized animals at many
      hindbrain sites stimulates breathing. The steady-state CO2 response in conscious
      animals is reduced by cell specific lesions of catecholamine, 5HT or neurokinin-1
      receptor (NK1R) expressing neurons and by focal inhibition at the retrotrapezoid
      nucleus (RTN) and medullary raphe (MR). Is the steady-state CO2 response a
      physiologically relevant way to study central chemoreception? Central
      chemoreceptors also: (1) provide a 'tonic drive' to breathe, (2) are modified by
      and/or modulate other control systems, e.g., temperature and hypoxia, (3) affect
      breath-to-breath variability, (4) can respond dynamically to few breath changes
      in CO2, and (5) interact in complex ways. We contend that central chemoreceptors
      detect interstitial pH and thus monitor the balance of arterial PCO2, cerebral
      blood flow and neuronal/glial metabolism. They affect physiological control
      systems in many ways, perhaps not all measurable, via the study of the steady
      state CO2 response.

PMID- 18085298
TI  - Intrinsic chemosensitivity of individual nucleus tractus solitarius (NTS) and
      locus coeruleus (LC) neurons from neonatal rats.
AB  - Chemosensitive (CS) neurons are found in discrete brainstem regions, but whether
      the CS response of these neurons is due to intrinsic chemosensitivity of
      individual neurons or is mediated by changes in chemical and/or electrical
      synaptic input is largely unknown. We studied the effect of synaptic blockade
      (11.4 mM Mg2+/0.2mM Ca2+) solution (SNB) and a gap junction uncoupling agent
      carbenoxolone (CAR--100 microM) on the response of neurons from two CS brainstem
      regions, the NTS and the LC. In NTS neurons, SNB decreased spontaneous firing
      rate (FR). We calculated the magnitude of the FR response to hypercapnic acidosis
      (HA; 15% CO2) using the Chemosensitivity Index (CI). The percentage of NTS
      neurons activated and CI were the same in the absence and presence of SNB.
      Blocking gap junctions with CAR did not significantly alter spontaneous FR. CAR
      did not alter the CI in NTS neurons and resulted in a small decrease in the
      percentage of activated neurons, which was most evident in NTS neurons from rats
      younger than postnatal day 10. In LC neurons, SNB resulted in an increase in
      spontaneous FR. As with NTS neurons, SNB did not alter the percentage of
      activated neurons or the CI in LC neurons. CAR resulted in a small increase in
      spontaneous FR in LC neurons. In contrast, CAR had a marked effect on the
      response of LC neurons to HA: a reduced percentage of CS LC neurons and decreased
      CI. In summary, both NTS and LC neurons appear to contain intrinsically CS
      neurons. CS neurons from the two regions receive different tonic input in slices
      (excitatory for NTS and inhibitory for LC); however, blocking chemical synaptic
      input does not affect the CS response in either region. In NTS neurons, gap
      junction coupling plays a small role in the CS response, but gap junctions play a
      major role in the chemosensitivity of many LC neurons.

PMID- 18085299
TI  - Chemosensitive neuronal network organization in the ventral medulla analyzed by
      dynamic voltage-imaging.
AB  - Central chemosensitivity is critically important to maintain homeostasis. e have
      successfully applied a voltage-imaging technique to medullary slice and isolated
      brainstem-spinal cord preparations and analyzed chemosensitive neuronal network
      organization in the rat ventral medulla. Our results indicate that neurons in the
      superficial ventral medullary chemosensitive regions and deeply located medullary
      respiratory neuronal network are interconnected. We propose a neuronal network
      organization model for central chemoreceptors.

PMID- 18085300
TI  - The effects of a respiratory acidosis on human heart rate variability.
AB  - Human heart rate variability (HRV) was examined during a mild respiratory
      acidosis induced by inhalation of a normoxic hypercapnic gas mixture. On two
      separate occasions, separated by 72 but not more than 120hr, ECG was recorded
      from 9 normotensive subjects during supine rest. ECG was recorded for 20 min
      breathing room air or a 5% CO2 in normoxic air mixture. Expired V'E, O2 and CO2
      were measured with breath-by-breath mass spectrometry. HRV spectra were
      calculated using a Welch averaged periodogram method and banded as Very Low
      Frequency (VLF: 0 - 0.04 Hz), Low Frequency (LF: 0.04 - 0.15 Hz), and High
      Frequency (HF: 0.15 - 0.4Hz). Student paired samples t-tests were used to compare
      room air (RA) versus inhaled 5% CO2 in air (5% CO2) data. All results reported as
      mean +/- SD. In the HRV time domain, hypercapnic normoxia reduced mean r-r
      intervals (5% CO2: 956.1 +/- 149.2 vs. RA: 1035 +/- 146.8 ms, p = 0.022) and
      median r-r intervals (5% CO2: 942.6 +/- 153.1 vs. RA: 1047.8 +/- 157.3 ms, p =
      0.010), and increased heart rates (5% CO2: 64.4 +/- 12 vs. RA: 59.3 +/- 10.1 bpm,
      p = 0.019). In the HRV frequency domain, hypercapnic normoxia increased the high
      frequency component of HRV (5% CO2: 9799 +/- 7649 vs. RA: 4399 +/- 3857 ms2, p =
      0.004) and reduced the LF/HF ratio (5% CO2: 0.243 +/- 0.145 vs. RA: 0.906 +/-
      0.672, p = 0.017). An incomplete ventilatory compensation probably accounts for
      the increased HF contribution. An increased heart rate with a mild respiratory
      acidosis may be caused by a vasodilator effect of elevated arterial PCO2,
      stimulating the increase in heart rate to maintain blood pressure.

PMID- 18085301
TI  - Neurokinin-1 receptor activation in the Botzinger complex evokes bradypnea and is
      involved in mediating the Hering-Breuer reflex.
AB  - The role of substance P (SP) and its receptor, the neurokinin-1 (NK1R), in the
      generation of respiratory rhythm has received considerable attention,
      particularly at the Pre-Botzinger Complex of the ventral respiratory group (VRG).
      However, the functional role of SP and NK1R in other VRG regions has not been
      explored in detail. We review the current literature and describe recent data
      demonstrating that selective activation of NK1R in the Botzinger Complex (BotC)
      of the VRG evoked bradypnea by lengthening expiratory period. In addition,
      endogenous activation of NK1R in the BotC participates in the expiratory
      lengthening effect of the Hering-Breuer reflex. These data suggest that NK1R
      expressing neurons in different subregions of the VRG have functionally diverse
      roles and provide new insight on the modulatory role of SP on respiratory
      reflexes.

PMID- 18085302
TI  - Brainstem catecholaminergic neurons modulate both respiratory and cardiovascular
      function.
AB  - Catecholamine neurons (CA) located in the brainstem project widely in the
      forebrain, hindbrain and spinal cord to many regions involved in the control of
      respiratory and cardiovascular function. For example, A6 noradrenergic neurons
      provide a tonic excitatory stimulus that maintains breathing frequency while A5
      neurons provide an inhibitory influence on both cardiovascular and respiratory
      function to slow breathing frequency and heart rate. Mice with genetic defects
      that include CA neurons have abnormal respiration and blood pressure. For
      example, mice heterozygous for Phox2b with CA neuron defects have sleep
      disordered breathing, and DBH knockout mice with absent CA cells centrally and
      peripherally have hypotension. Our hypothesis is that widespread brainstem CA
      neuron lesions in adult rats would significantly affect cardiorespiratory
      functions including breathing, chemoreception, blood pressure and heart rate. We
      produced the widespread brainstem CA neuron lesion by injecting anti-dopamine
      beta-hydroxylase-saporin (DBH-SAP) via the 4th ventricle. The lesioned group had
      a 64-84% loss of A5, A6 and A7 tyrosine hydroxylase immunoreactive (ir) neurons
      along with 56-64% loss of C1 and C2 phenyl ethanolamine-N methyltransferase
      (PNMT)-ir neurons over 2-3 weeks. The significant respiratory changes included:
      (1) a decreased breathing frequency during air and 7% CO2 breathing in both
      wakefulness and non-REM (NREM) sleep; (2) a reduced ventilatory response to 7%
      CO2 in wakefulness (-28%) and in NREM sleep (-26%); and (3) increased variability
      of breathing in REM sleep but not in wakefulness or NREM sleep. Significant
      cardiovascular changes at two weeks included: (1) an increased MAP by 11.7mmHg in
      the room air resting condition; (2) an unaffected cardiovascular response to
      hypercapnia; and (3) a smaller decrease of MAP in response to hypoxia.
      CONCLUSIONS: Central CA neurons have a net excitatory effect on breathing and
      chemoreception but a net inhibitory effect on blood pressure.

PMID- 18085303
TI  - Responses of brainstem respiratory neurons to activation of midbrain
      periaqueductal gray in the rat.

PMID- 18085305
TI  - Modulation of Hering-Breuer reflex by ventrolateral pons.
AB  - The vagally-mediated Hering-Breuer reflex (HBR) is known to be modulated by the
      classic pneumotaxic center in the dorsolateral pons. In this work, we
      investigated whether the HBR was also modulated by the ventrolateral pons (vl
      pons). Experiments were performed on urethane anesthetized adult rats. The HBR
      was elicited by electrical stimulation of the vagus nerve and its strength was
      compared before and after electrical stimulation or microinjection of MK-801 (non
      competitive NMDA receptor antagonist) at the vl-pons. We found that the
      inspiratory inhibition and expiratory prolongation effects of the HBR were
      strengthened after electrical stimulation at the vl-pons but were weakened after
      microinjecting MK-801. Results suggested that the vl-pons could influence the
      respiratory rhythm by modulating the strength of HBR via NMDA receptor-mediated
      neurotransmission.

PMID- 18085304
TI  - Computational model of TASK channels and PKC-pathway dependent serotonergic
      modulatory effects in respiratory-related neurons.
AB  - Hypoglossal motoneurons (HMs) receive serotonergic innervations from medullary
      raphe neurons and produce rhythmic discharge patterns closely associated with
      respiratory rhythm generated in the pre-Botzinger complex (pBC). HM activity is
      subject to modulation by numerous factors including serotonin (5-HT), TRH,
      norepinephrine (NE), substance P (SP), pH, multiple protein kinases and
      phosphatases. In this present work, we introduce a computational HM model that
      facilitates the investigation of how neuromodulatory factors such as 5-HT and pH,
      can affect HM activities.

PMID- 18085306
TI  - Respiratory network complexity in neonatal rat in vivo and in vitro.
AB  - Numerous experimental preparations from neonatal rodents have been developed to
      study mechanisms responsible for respiratory rhythm generation. Amongst them, the
      in vivo anesthetized neonatal rat preparation and the in vitro medullary slice
      preparation from neonatal rat are commonly used. These two preparations not only
      contain a different extent of the neuroanatomical axis associated with central
      respiratory control, but they are also studied under markedly different
      conditions, all of which may affect the complex dynamics underlying the central
      inspiratory neural network. Here, we evaluated the approximate entropy (ApEn)
      underlying inspiratory motor bursts as an index of inspiratory neural network
      complexity from each preparation to address this possibility. Our findings
      suggest that the central inspiratory neural network of the in vivo anesthetized
      neonatal rat exhibits lower complexity (i.e., more order) than that observed in
      the in vitro transverse medullary slice preparation, both of which are
      substantially lower than that observed in more intact in vitro (e.g., arterially
      perfused rat) and mature in vivo (e.g., anesthetized rat, piglet, cat)
      preparations. We suggest that additional studies be conducted to identify the
      precise mechanisms responsible for the differences in central inspiratory neural
      network complexity between these two neonatal rat preparations.

PMID- 18085307
TI  - Fast oscillatory rhythms in inspiratory motor discharge: a mathematical model.
AB  - In this paper, a mathematic model is applied to characterize spectral activity
      associated with fast oscillatory rhythms inherent in inspiratory discharges.
      Based on the estimated parameters, features are extracted to allow the model to
      discriminate between changes in the location, magnitude, and shape of spectral
      activities under basal conditions and during pharmacological blockade of gap
      junctions.

PMID- 18085308
TI  - Burst-to-Burst variability in respiratory timing, inspiratory-phase spectral
      activity, and inspiratory neural network complexity in urethane-anesthetized
      C57BL/6 mice in vivo.
AB  - Recent work from our laboratory has focused on identifying burst-to-burst
      variability in temporal and spectral characteristics for 5-minute time series
      segments of basal inspiratory motor discharges from urethane-anesthetized adult
      C57BL/6 mice. The current investigation, as the continuation of our previous
      studies, examined short- and long-term burst-to-burst variability in temporal and
      spectral components as well as in complexity, which reflects the central
      respiratory network dynamics. All measures were assessed by quantitative poincare
      plot analyses and the determination of the coefficient of variation.

PMID- 18085309
TI  - Effects of hypercapnia on non-nutritive swallowing in newborn lambs.
AB  - The purpose of this study was to determine the effect of hypercapnia on non
      nutritive swallowing (NNS) frequency and on NNS-breathing coordination in newborn
      lambs. Six lambs were chronically instrumented for recording
      electroencephalogram, eye movements, diaphragm and thyroarytenoid muscle
      activity, nasal airflow and electrocardiogram. Each lamb was placed in a
      Plexiglas chamber and exposed to a hypercapnic gas mixture (21% O2, 5% CO2).
      Polysomnographic recordings were conducted in non-sedated lambs using a custom
      designed radiotelemetry system. Results show that hypercapnia increased NNS
      frequency in all three states of alertness (p < 0.0001 to 0.03), through a
      specific increase in ie-type NNS. Causal mechanisms and potential consequences of
      such observations on aspirations and apneas, as well as on swallowing maturation,
      will require further studies.

PMID- 18085310
TI  - CPAP inhibits non-nutritive swallowing through stimulation of bronchopulmonary
      receptors.
AB  - While swallowing and respiratory problems are among the most frequent disorders
      encountered in neonates, the interrelationships between both functions are not
      completely understood. This is especially true for non-nutritive swallowing
      (NNS), which fulfills the important function of clearing upper airways from both
      local secretions and liquids refluxed from the stomach. Recently, we showed that
      nasal CPAP inhibits NNS during quiet sleep in the newborn lamb (Samson, St
      Hilaire, Nsegbe, Reix, Moreau-Bussiere and Praud 2005). The present study was
      aimed at testing the hypothesis that NNS inhibition is eliminated when CPAP is
      directly administered through a tracheostomy, thus eliminating reflexes
      originating from upper airway receptors. Results show that both nasal and
      tracheal CPAP 6cm H2O similarly inhibit total NNS during quiet sleep, thus
      suggesting that the inhibiting effect of nasal CPAP on NNS is mainly mediated
      through bronchopulmonary mechanical receptors with minimal participation of the
      upper airways.

PMID- 18085311
TI  - Glutamatergic neurotransmission is not essential for, but plays a modulatory role
      in, the production of gasping in arterially-perfused adult rat.
AB  - Glutamatergic neurotransmission appears to be essential for generation of the
      eupneic pattern of inspiratory motor discharge as well as the expression of
      inspiratory-phase synchronization. The role of glutamatergic neurotransmission in
      the generation of gasping, including its accompanying modulation of spectral
      activity, is less well understood. The current investigation was, therefore,
      undertaken to investigate the effects of blockade of ionotropic glutamate
      receptors on (1) the generation and expression of gasping and (2) the magnitude
      and timing of spectral activity during gasping using an arterially-perfused
      decerebrate adult rat preparation. Our findings suggest that glutamatergic
      neurotransmission is not required for the production of gasping, but it may play
      a modulatory role in the expression of both the temporal and spectral
      characteristics of phrenic nerve discharge during gasping.

PMID- 18085312
TI  - Potential mechanism for transition between acute hypercapnia during sleep to
      chronic hypercapnia during wakefulness in obstructive sleep apnea.
AB  - This paper presents a series of experiments, both in patients and computer
      models, investigating the transition from acute to chronic hypercapnia in OSA.
      The data demonstrate that acute hypercapnia during periodic breathing occurs due
      to either reduction in magnitude of inter-event ventilation and/or reduction in
      inter-event ventilatory duration relative to duration of the preceding event. The
      transition between acute hypercapnia during sleep and chronic sustained
      hypercapnia during wakefulness may be determined by an interaction between
      respiratory control and renal handling of HCO3-.

PMID- 18085313
TI  - Biochemical control of airway motor neurons during rapid eye movement sleep.

PMID- 18085314
TI  - Prediction of periodic breathing at altitude.

PMID- 18085315
TI  - A negative interaction between central and peripheral respiratory chemoreceptors
      may underlie sleep-induced respiratory instability: a novel hypothesis.
AB  - Central (brainstem) and peripheral (carotid body) respiratory chemoreflexes act
      in concert to modulate breathing during sleep, maintaining blood gases (PCO2 and
      PO2) within narrow limits. Increases in both central and peripheral chemoreflex
      gain have been reported in clinical populations that experience central sleep
      apnoea and likely underlie the pathophysiology of this disorder. However, how
      central-peripheral chemoreceptor interaction affects the apparent gain of each
      chemoreflex is controversial. Data from our laboratory demonstrate that there is
      a negative interaction between central and peripheral chemoreceptors in the rat,
      such that brainstem hypocapnia augments peripheral chemoreflex gain in response
      to both carotid body PCO2 and PO2. We note that a negative interaction may also
      occur in humans, especially relevant in those experiencing chronic hypocapnia.
      Interestingly, chronic hypocapnia occurs in populations prone to central sleep
      apnea, such as congestive heart failure (CHF) patients and individuals sleeping
      at high altitude. These observations lead us to propose the novel hypothesis that
      a negative interaction between chemoreceptors results in an augmented peripheral
      chemoreceptor gain when the central chemoreceptors are hypocapnic, thereby
      contributing directly to breathing instability during sleep.

PMID- 18085316
TI  - Ventilatory response to hypercapnia in pre-menopausal and post-menopausal women.

PMID- 18085317
TI  - Oxidative stress impairs upper airway muscle endurance in an animal model of
      sleep-disordered breathing.
AB  - Obstructive sleep apnoea is characterised by intermittent hypoxia due to
      recurrent obstructions of the pharyngeal airway during sleep. We have shown that
      chronic intermittent hypoxia impairs respiratory muscle function and CNS control
      of upper airway patency. In this study, we tested the hypothesis that disruption
      of an endogenous antioxidant defence system exacerbates the effects of
      intermittent hypoxia on upper airway muscle contractile function. Thirty-two male
      Wistar rats were placed in restrainers with their heads in hoods in which the
      ambient oxygen concentration could be modified by controlling the gas supply to
      the hoods. Sixteen rats were exposed to alternating equal periods of hypoxia and
      normoxia, twice per minute, 8 hours per day for 1 week. The remaining 16 animals
      were exposed to normoxia continuously under identical experimental conditions. In
      both groups, half the animals received daily injections of buthionine sulfoxamine
      (BSO), an inhibitor of the rate-limiting enzyme in glutathione synthesis. The
      other half received daily vehicle injections. At the end of the 1-week treatment
      period, the sternohyoid muscles were removed and fatigue characteristics were
      determined in vitro. Intermittent hypoxia was associated with a decrease in
      sternohyoid muscle endurance, an effect that was exacerbated by treatment with
      BSO. In separate experiments, daily treatment with the antioxidant N-acetyl
      cysteine blocked the deleterious effects of intermittent hypoxia on respiratory
      muscle function. We suggest that oxidative stress contributes to impaired upper
      airway muscle endurance in our animal model and that endogenous glutathione may
      be especially important in limiting free radical-induced muscle dysfunction. Our
      results may have particular relevance to respiratory disorders associated with
      recurrent hypoxia, such as the sleep apnoea/hypopnoea syndrome.

PMID- 18085318
TI  - Ventilatory and blood pressure responses to isocapnic hypoxia in OSA patients.

PMID- 18085319
TI  - Modeling of sleep-induced changes in airway function: implication for nocturnal
      worsening of bronchial asthma.
AB  - Here we describe the model of sleep-induced worsening of airway function in
      patients with airway disorders. Our model is based on the noradrenergic pathways
      that link central neuronal structures responsible for alternating wakefulness and
      sleep with the neuronal networks regulating the activity of airway-related vagal
      preganglionic neurons (AVPNs). Our previous studies showed that cholinergic
      outflow to the airways depend on the activity of inhibitory inputs to AVPNs.
      Major inhibitory cell groups, regulating AVPNs discharge, include brainstem
      noradrenaline (NA)-containing cells receiving projections from the hypothalamic
      sleep-promoting neurons of the ventrolateral preoptic region (VLPO). When
      activated, VLPO cells, using GABA and/or galanin as mediators, downregulate the
      activity of inhibitory NA neurons projecting to AVPNs. Therefore, changes that
      occur during sleep lead to a shift from inhibitory to excitatory transmission of
      the AVPNs, thereby increasing cholinergic outflow to the airways. Our model,
      based on neuroanatomical and molecular studies, and physiology experiments, can
      be used to explain sleep-related worsening of bronchial asthma and might
      contribute to development of clinically meaningful treatment for patients with
      sleep-induced worsening of airway function and respiratory symptoms.

PMID- 18085320
TI  - The effects of wakefulness state on the temporal characteristics of ventilatory
      variables in man.
AB  - The effects of audiovisual stimulation on the temporal patterns of V(T), T(I),
      T(E) were studied in 11 healthy subjects. 75 datasets of steady-state breathing
      each of eight minutes in duration were obtained during low wakefulness (lying
      still, eyes closed), low wakefulness with calibrated thermal pain stimulation and
      high wakefulness (playing a computer game). The analysis included removal of
      trend and mean, interpolation and re-sampling of the data to provide an equi
      spaced time basis, test for normal distribution of datasets, power spectral
      estimation, estimation of the parameters of 1st and 2nd order autocorrelation
      models and estimation of the same parameters on the residuals following
      subtraction of the 1st or 2nd order models. All power spectra showed the highest
      power at the lowest frequencies; correspondingly the 1st order autocorrelation
      coefficients were significant at the 5% level except for T(E) (p = 0.12). The 2nd
      order coefficients were non-significant for all series. The 1st order
      autocorrelation coefficients of the residuals (after subtraction of the 1st order
      autocorrelation component) were all non-significant. With 1st order
      autocorrelation coefficients averaging between .12 and .37 the non-random part of
      the variation explained by the 1st order autocorrelation structure is between
      1.4% and 13.7% and independent of stimulation of breathing by thermal or mental
      stimuli.

PMID- 18085321
TI  - Cerebral blood flow and ventilatory sensitivity to CO2 measured with the modified
      rebreathing method.
AB  - The ventilatory response to carbon dioxide (CO2) measured by modified rebreathing
      (SrVE) is closer to that measured by the steady-state method (SsVE) than is the
      response measured by Read's rebreathing method. Furthermore, the value estimated
      by the steady-state method depends upon the number of data points used to measure
      it. We planned to assess if these observations were also true for cerebral blood
      flow (CBF), as measured by steady-state (SsCBF) and modified rebreathing (SrCBF)
      tests. Six subjects undertook two protocols, one in the steady-state and one with
      modified rebreathing. SsVE depended upon the number of data points used to
      calculate it, and SsVE and SrVE were similar. However, this was not the case with
      SsCBF, and SsCBF was much higher than SrCBF. These findings are consistent with
      the notions that the specific CO2 stimulus differs for CBF control as compared
      with ventilation (VE) control, and that prior hypocapnia has an effect on CBF and
      VE for longer than the duration of the hypocapnia.

PMID- 18085322
TI  - Naloxone reversal of opioid-induced respiratory depression with special emphasis
      on the partial agonist/antagonist buprenorphine.
AB  - Buprenorphine is relatively resistant to reversal by naloxone. We tested the
      effect of various doses and infusion schemes of naloxone on buprenorphine-induced
      respiratory depression and compared the data with naloxone-reversal of morphine
      and alfentanil-induced respiratory depression. Both morphine and alfentanil were
      easily reversed by low doses of naloxone (0.4 mg). Increasing doses of naloxone
      caused a bell-shaped reversal curve of buprenorphine with maximal reversal at
      naloxone doses between 2 and 4 mg. However, reversal was short-lived. The bell
      shaped reversal curve may be related to the existence of two mu-opioid receptor
      subtypes, one mediating the agonist effects of opioids at low dose, the other
      mediating antagonistic effects at high dose.

PMID- 18085323
TI  - The pulse oxygen saturation: inspired oxygen pressure (SpO2:PIO2) diagram:
      application in the ambulatory assessment of pulmonary vascular disease.
AB  - BACKGROUND: The inspired oxygen to pulse saturation (SpO2:PIO2) curve mirrors the
      oxyhaemoglobin dissociation curve but is shifted to the right by the difference
      between inspired and alveolar oxygen fractions. Inspection of the curve has been
      used to discern changes in shunt. AIMS: We aimed to demonstrate the SpO2: PIO2
      curve's quantification using readily available software, and its clinical utility
      in assessing ambulatory patients. METHODS: Six normal and seven hereditary
      haemorrhagic telangiectasia (HHT) clinic patients have been studied. After
      measuring barometric pressure, seated subjects were monitored with finger probe
      pulse oximetry while breathing increasing fractions of humidified oxygen through
      a Venturi mask until either their SpO2 or PIO2 was 100%. Resulting SpO2 and PIO2
      values were plotted, fitted, assessed for goodness-of-fit and compared using the
      free, open source nonlinear regression extension package drc for the R
      programming language whose accuracy was also tested against two NIST reference
      sigmoidal curve datasets. RESULTS: All reference, individual and collected normal
      results were well fitted by the drc software with highly insignificant goodness
      of-fit F tests. The laboratory normal curve was identically fitted by symmetrical
      Hill and asymmetrical Weibull functions. Although normal and negative HHT
      screening patient curves did not differ, there were significant differences
      between normal, pre-treatment (shunt fraction 9.44%), and post-treatment HHT
      curves. CONCLUSION: Nonlinear regression analysis of the SpO2:PIO2 curve permits
      valid, simple, safe, noninvasive, sensitive and cheap estimation of shunt in
      ambulatory patients.

PMID- 18085324
TI  - Hypocapnia and airway resistance in normal humans.

PMID- 18085325
TI  - Disturbances of breathing in Rett syndrome: results from patients and animal
      models.

PMID- 18085326
TI  - NHE3 in the human brainstem: implication for the pathogenesis of the sudden
      infant death syndrome (SIDS)?
AB  - Previous studies have demonstrated an inverse correlation between the degree of
      respiratory drive and NHE3 mRNA expression in the brainstem of awake rabbits.
      Here we show that the levels of NHE3 mRNA extractable from kryo-conserved tissue
      are highly variable also in the human brainstem. As an insufficient drive to
      breath may be a final event causing sudden infant death, we compared the
      expression of NHE3 mRNA in a collective of children who died from non-natural
      causes to an equal number of SIDS victims. Evaluation of signals from NHE3 RT-PCR
      showed higher values for the SIDS collective than for the control group. We
      suggest that the level of NHE3 expression in brainstem tissue may contribute to
      the vulnerability of infants for SIDS.

PMID- 18085327
TI  - The ventilatory response to exercise does not differ between obese women with and
      without dyspnea on exertion.

PMID- 18085328
TI  - Molecular modes of action of cytotoxic alkaloids: from DNA intercalation, spindle
      poisoning, topoisomerase inhibition to apoptosis and multiple drug resistance.

PMID- 18085329
TI  - Calystegines.

PMID- 18085330
TI  - Recent studies on the synthesis of strychnine.

PMID- 18085331
TI  - Alkyl, aryl, alkylarylquinoline, and related alkaloids.
AB  - The Rutaceae continues to be the primary source of new alkyl-, aryl-, and
      alkylarylquinolin/ones. In the past 17 years, the overall distribution of these
      alkaloid types within the family has changed little since the chemosystematics
      reviews by Waterman (270), Mester (40), and da Silva et al. (279).
      Alkylquinolones dominate the reported isolations with about 51% of the total,
      with arylquinolones (16%), alkylquinolines (15%), alkylarylquinolines (11%),
      arylquinolines (3%), alkylarylquinolones (2%), and quinolines (2%) as the
      significant structural groups contributing to the remainder of this class of
      alkaloids. The alkyl-, aryl-, and alkylarylquinolin/one alkaloids occur in 50
      species belonging to 24 genera and 6 subfamilies. Despite the intensive chemical
      exploration of many species from other plants in the Rutales family, but not in
      the family Rutaceae, the first alkaloid alkylquinolone from a simaroubaceous
      plant (160) was not reported until 1997. Although many additional alkaloids have
      been reported, some of new structural types (Bo.4), substantial biosynthetic work
      on plant-derived alkylquinolin/ones has not yet been carried out. The
      biosynthesis of some of these alkaloids in bacteria was firmly established as
      being derived from anthranilic acid. Outside of the Rutales, alkyl-, aryl-, and
      alkylarylquinolin/ones have not been found, except for simple quinoline (A.1;
      only one) and 2-methylquinoline derivatives in the Zygophyllaceae, and only an
      atypical quinolone derivative (Ao.1) in the Asteraceae family. A few 3
      phenylquinolines (2), 3-(1H-indol-3-yl)quinoline (1), and quinoline-quinazoline
      (1) alkaloids have been reported from only a single genus in the Zygophyllaceae.
      Tryptophan-derived quinolines in higher plants are confined to a few 2
      carboxylicquinolin/ones (6) and 4-carbaldehydequinolines (5); the former found in
      the Ephedraceae (5), Boraginaceae (1), Fagaceae (1), Ginkgoaceae (1),
      Plumbaginaceae (1), Solanaceae (1), and Apiaceae (1), and the latter in the
      Moraceae (3), Alliaceae (1), and Pontederiacae (1). The number of quinolones
      derived from glycine and a polyketide is also limited. 5-Alkyl-2-methylquinolin
      4(1H)-ones (8) occur in the Euphorbiaceae, and 5-alkyaryl-2-methylquinolin-4(1H)
      ones ((3) in the Sterculiaceae. Alkylquinolin/ones are well-known as typical
      alkaloids of three Proteobacteria and three Actinobacteria; the genus Pseudomonas
      yielded the majority (46%) of the total number of alkaloids reported (39). 2
      Carboxylicquinolin/ones (4) and 4-carbaldehydequinolines (6) are minor
      constituents in both divisions of bacteria. More interesting are the
      quinolactacins (7), in which the second nitrogen is derived from L-valine or L
      isoleucine, recently reported to occur only in the fungus Penicillium. Many of
      these diverse alkaloids have served directly as medicines or as lead compounds
      for the synthesis (258) of derivatives with an improved biological profile. It is
      apparent from the summary view of the alkyl-, aryl-, and alkylarylquinolin/ones
      reported in the Rutaceae that they help to confirm the affinity between Rutoideae
      tribes and provide firm support for placing the Spathelioideae and the
      Dictyolomatoideae close to the more primitive Zanthoxyleae tribe. On the other
      hand, the bacteria and fungi are needed for more substantial chemical studies.
      When more data become available, it is likely that useful systematic correlations
      will emerge. More detailed studies regarding the biosynthetic pathways of the
      alkyl-, aryl-, and alkylarylquinolin/ones in the Rutaceae and in bacteria are
      needed. Such studies would clarify the differences in the pathways based on their
      derivation from anthranilic acid in bacteria and in rutaceous plants. Finally,
      this survey indicates that the Rutaceae, and various bacterial and fungal species
      offer considerable potential for the discovery of new or known alkaloids with
      significant and possibly valuable biological activities.

PMID- 18085332
TI  - Summaries of the SAGES 2007 reoperative minimally invasive surgery symposium.
AB  - This manuscript represents a compilation of summaries from the reoperative
      symposium at the SAGES 2007 conference in Las Vegas, Nevada. The symposium
      addressed reoperative laparoscopy for several common diseases including
      colorectal disease, gastroesophageal reflux, hernias, bariatric, and pediatric
      surgery. The preoperative assessment is crucial to the success of each procedure.
      Prior to any intervention the underlying functional, mechanical, or
      pathophysiological disorder must be identified to ensure the success of the
      reoperative laparoscopic procedure. The ensuing manuscript summarizes the oral
      presentations and discusses several technical aspects for each disorder.

PMID- 18085334
TI  - The assessment of a rapid noninvasive immunochromatographic assay test for fecal
      lactoferrin in patients with suspected inflammation of the ileal pouch.
AB  - PURPOSE: Pouchitis is a common complication after ileal pouch-anal anastomosis.
      Diagnosis is based on the Pouch Disease Activity Index, which comprises clinical
      symptoms, endoscopic appearance, and histologic confirmation. A Pouch Disease
      Activity Index > or = 7 confirms pouchitis. Fecal lactoferrin is a marker of
      intestinal inflammation, which can aid in the diagnosis of pouchitis. The IBD EZ
      VUE test is a simple, rapid, noninvasive test for fecal lactoferrin. Our goal was
      to study the sensitivity and specificity of this test in the diagnosis of
      pouchitis. METHODS: Consecutive patients with pouch dysfunction were recruited
      from October 2005 to July 2006. A fecal sample was collected before calculation
      of the Pouch Disease Activity Index. An IBD EZ VUE test was performed on each
      fecal sample and the results correlated with the diagnosis of pouchitis to
      calculate sensitivity and specificity of the IBD EZ VUE test. RESULTS: There were
      32 patients (21 healthy and 11 inflamed pouches). The IBD EZ VUE test was
      positive in 14 patients. It had a sensitivity of 100 percent and a specificity of
      86 percent in diagnosing pouchitis. The positive predictive value was 76 percent.
      There were three false-positive results. CONCLUSIONS: The IBD EZ VUE test is a
      sensitive method that may remove the need for invasive pouch investigations and
      lead to greater confidence when antibiotic therapy is commenced. Further
      investigations may be reserved for those patients who have a positive lactoferrin
      test and fail to respond to antibiotic treatment.

PMID- 18085333
TI  - Family history and serology predict Crohn's disease after ileal pouch-anal
      anastomosis for ulcerative colitis.
AB  - PURPOSE: Approximately 5 to 10 percent of patients undergoing ileal pouch-anal
      anastomosis with a diagnosis of ulcerative colitis are subsequently diagnosed
      with Crohn's disease. Preoperative predictors for Crohn's disease post-ileal
      pouch-anal anastomosis have not been prospectively defined. METHODS: A total of
      238 consecutive patients with ulcerative colitis or indeterminate colitis
      undergoing ileal pouch-anal anastomosis were prospectively enrolled into a
      longitudinal database. Clinical factors were assessed perioperatively. Serum
      drawn preoperatively was assayed for anti-Saccharomyces cerevisiae, antiouter
      membrane porin-C, anti-CBir1, and perinuclear antineutrophil cytoplasmic antibody
      using enzyme-linked immunosorbent assay. Crohn's disease was defined by small
      bowel inflammation proximal to the ileal pouch or a perianal fistula identified
      at least three months after ileostomy closure. Predictors were assessed in a
      multivariate Cox proportional hazards model to predict the rate of Crohn's
      disease after ileostomy closure. RESULTS: Sixteen patients (7 percent) were
      diagnosed with Crohn's disease; median time to Crohn's disease was 19 (range, 1
      41) months. Significant factors for postoperative Crohn's disease after ileal
      pouch-anal anastomosis included family history of Crohn's disease (hazard ratio,
      8.4; 95 percent confidence interval, 2.96-24.1; P < 0.0001) and anti
      Saccharomyces cerevisiae immunoglobulin-A seropositivity (hazard ratio, 3.14; 95
      percent confidence interval, 1.1-9.81; P = 0.04). Crohn's disease developed in
      only 8 of 198 patients (4 percent) without these predictors vs. 8 of 40 patients
      (20 percent) in those with at least one of these factors (P = 0.002). The
      cumulative risk of Crohn's disease among patients with two risk factors (67
      percent) was higher than in patients with either risk factor (18 percent) or
      neither risk factor (4 percent, P < 0.001). CONCLUSIONS: Patients with ulcerative
      colitis and indeterminate colitis with a family history of Crohn's disease or
      preoperative anti-Saccharomyces cerevisiae immunoglobulin-A seropositivity are
      more likely to be diagnosed with Crohn's disease after ileal pouch-anal
      anastomosis.

PMID- 18085335
TI  - Fecal incontinence: the quality of reported randomized, controlled trials in the
      last ten years.
AB  - PURPOSE: This study was designed to analyze the characteristics and the quality
      of reporting of randomized, controlled trials published during the last ten years
      on fecal incontinence. METHODS: An electronic search for all randomized,
      controlled trials on fecal incontinence was undertaken by using the MEDLINE
      database via PubMed. The data collected were divided into general data,
      characteristics of reporting, methodology quality assessment using the Jadad
      scale and a validated methodology quality score (MINCIR score), evaluation of the
      items published in the CONSORT statement, and the journal impact factor. Reports
      were divided into two groups: published articles from 1996 to 2000 (Group 1), and
      from 2001 to 2005 (Group 2). RESULTS: Forty-two trials fulfilled the inclusion
      criteria of the study (Group 1, n = 15; and Group 2, n = 27). There were no
      significant differences in general characteristics of randomized, controlled
      trials between the two groups. In Group 2, there were a statistically significant
      higher number of studies that reported a flow chart (P < 0.001), written informed
      consent (P = 0.008), sample size calculation (P = 0.023), and withdrawals and
      dropouts (P < 0.001). We found a statistically significant higher score in Jadad
      scale (P = 0.046) and MINCIR score (P = 0.016) in the published studies in Group
      2. Also we found higher journal impact factor of journals that published these
      randomized, controlled trials during the most recent years (P = 0.04).
      CONCLUSIONS: There is a lack of high-quality reported randomized, controlled
      trials on fecal incontinence during the last ten years. Reports of randomized,
      controlled trials involving patients with fecal incontinence published after 2001
      were better reported than in the previous five years.

PMID- 18085336
TI  - Assessment of the risk factors for colonic diverticular hemorrhage.
AB  - PURPOSE: Colonic diverticulosis, although usually asymptomatic, sometimes causes
      diverticular hemorrhage. Studies about risk factors, other than nonsteroidal anti
      inflammatory drugs, for colonic diverticular hemorrhage are limited. We conducted
      the present study to elucidate their significance as a risk factor. METHODS:
      Colonic diverticulosis was found in 1,753 patients and diverticular hemorrhage in
      44 patients among 9,499 total colonoscopy examinees at the authors' institutions
      between September 1995 and December 2005. After reviewing their clinical
      features, we chose two controls for each case with diverticular hemorrhage
      matched for age, gender, and the location of diverticulosis. We evaluated the
      effects of comorbidities (hypertension, hyperlipidemia, diabetes mellitus,
      cerebrovascular disease, ischemic heart disease), habits (alcohol, smoking), and
      medications, including nonsteroidal anti-inflammatory drugs, by using conditional
      logistic regression analysis. RESULTS: There were no significant differences
      between patients with diverticular hemorrhage and those with nonbleeding
      diverticulosis regarding age (67 +/- 13 vs. 64 +/- 11 years) or gender ratio
      (male/female ratio: 36/8 vs. 1,237/472). As for location, the proportion of
      bilateral diverticulosis was larger among patients with hemorrhage (43 vs. 22
      percent). In the case-control study, nonsteroidal anti-inflammatory drugs (odds
      ratio, 15.6; 95 percent confidence interval, 1.1-214; P = 0.04), hypertension
      (odds ratio, 6.6; 95 percent confidence interval, 2.1-20.5; P = 0.0011), and
      aspirin and/or other anticoagulant (odds ratio, 3; 95 percent confidence
      interval, 1.04-8.6; P = 0.042) were shown to be significant risk factors by
      multivariate analysis. CONCLUSIONS: Hypertension, nonsteroidal anti-inflammatory
      drugs, and anticoagulants, including aspirin, are independent risk factors for
      colonic diverticular hemorrhage.

PMID- 18085337
TI  - Fine-tuning of the extent of lateral internal sphincterotomy: spasm-controlled
      vs. up to the fissure apex.
AB  - PURPOSE: This study was designed to compare the results of controlled lateral
      internal sphincterotomy by using anal calibrators with those of sphincterotomy up
      to the fissure apex in a randomized, prospective fashion. METHODS: In the fissure
      apex group, sphincterotomy was extended to the level of the fissure apex, and in
      the spasm-controlled group, serial small sphincterotomies and anal caliber
      measurements followed until an anal caliber of 30 mm was obtained. RESULTS: The
      preoperative anal caliber was 24 +/- 1.9 (range, 20-28) mm and 24.9 +/- 2.44
      (range, 19-28) mm in the spasm-controlled and fissure apex groups, respectively
      (P = 0.127). Postoperatively, the spasm-controlled group had a mean anal caliber
      of 31.5 +/- 1.28 (range, 30-32) mm, and the fissure apex group had 32.5 +/- 2.33
      (range, 25-37) mm (P = 0.035). In the fissure apex group, a significant negative
      correlation was determined between the postoperative anal caliber and time of
      relief of pain (r = -0.568, P = 0.001). The early (7 and 28 days) postoperative
      anal incontinence scores were significantly higher in the fissure apex group (P =
      0.002, P < 0.0001, respectively). A significant positive correlation between the
      anal caliber measurements and anal incontinence scores at 28 days and 2 months
      also was noted in the fissure apex group (r = 0.406, P = 0.023; and r = 0.364, P
      = 0.044). CONCLUSIONS: Controlled sphincterotomy provided a faster relief of
      pain, and it was associated with a lower rate of early postoperative disturbance
      of continence and an insignificantly lower rate of treatment failure compared
      with sphincterotomy up to the fissure apex.

PMID- 18085338
TI  - Nodal harvest: surgeon or pathologist?

PMID- 18085339
TI  - Laparoscopic- vs. hand-assisted ultralow anterior resection: a prospective study.
AB  - PURPOSE: A standard laparoscopic-assisted operation can be conducted with
      colorectal anastomosis performed after extraction of specimen and insertion of a
      pursestring via a small left iliac fossa or suprapubic incision, or completed via
      hand-assisted laparoscopic technique with a 7-cm to 8-cm suprapubic incision.
      This study compares the short-term outcomes of either technique. METHODS: Sixty
      three consecutive patients undergoing laparoscopic-assisted ultralow anterior
      resection or total mesorectal excision for rectal cancer were examined. The
      laparoscopic-assisted group (n = 31) had standard laparoscopic-assisted
      resection, whereas the hand-assisted laparoscopic group (n = 32) had a 7-cm to 8
      cm suprapubic incision to allow an open colorectal anastomosis. In patients who
      were obese or have had multiple abdominal surgeries, the hand-assisted approach
      was generally favored. All patients had a diverting ileostomy. RESULTS: There was
      no conversion in either group. Mean operating time was significantly longer in
      the laparoscopic-assisted group (188.2 vs. 169.8 minutes; P < 0.0001). Mean
      duration for narcotic analgesia (1.65 vs. 3.38 days, P < 0.0001), mean time to
      flatus (1.97 vs. 3.19 days, P < 0.0001), and mean duration of intravenous
      hydration (2.45 vs. 3.88 days, P < 0.0001) were longer in the hand-assisted
      laparoscopic group. However, the mean length of hospital stay (5.8 vs. 5.9 days,
      P = 0.379) was similar. There was no major surgical complication in either group;
      chest infection, wound infection, and thrombophlebitis were similar between the
      laparoscopic-assisted group and the hand-assisted laparoscopic group. Adequacy of
      specimen harvest (distal tumor margins, P = 0.995; circumferential resection
      margin, P = 0.946; number of lymph nodes, P = 0.845) was similar. CONCLUSIONS:
      Although both laparoscopic-assisted and hand-assisted laparoscopic surgeries are
      safe and feasible for ultralow anterior resection, the hand-assisted technique
      significantly shortens operating time.

PMID- 18085340
TI  - 4-methylquinazoline is a minor component of the male sex pheromone in Nasonia
      vitripennis.
AB  - We identified 4-methylquinazoline (4-MeQ) as a minor component of the male sex
      pheromone of the parasitoid Nasonia vitripennis. Like the major components
      (4R,5R)- and (4R,5S)-5-hydroxy-4-decanolide (HDL), 4-MeQ is synthesized in the
      abdomen of males. At doses of 6 or 1 ng, 4-MeQ synergized the response of virgin
      females to the HDL-diastereomers in a still-air olfactometer, but was not
      attractive as a single component. 4-MeQ is also responsible for the
      characteristic medicinal odor of N. vitripennis males.

PMID- 18085341
TI  - Albendazole is not effective for primary treatment of hepatic hydatid cysts.
AB  - INTRODUCTION: In current practice, minimal invazive interventions such as
      percutaneous drainage and laparoscopic surgery in adjunct treatment with
      benzimidazoles have been gaining acceptance in treatment of hydatid cystic
      disease with minimal morbidity and mortality. In this prospective study, the
      efficacy and validity of primary medical therapy in the treatment of hydatid
      cystic disease has been investigated. PATIENTS AND METHODS: Sixty-five patients
      with hepatic cystic disease were treated with albendazole alone between January
      2004 and June 2007. All of the patients were administrated albendazole as 10 mg
      kg(-1) day(-1) divided into two equal doses for 6 months with ultrasonography
      (USG), serological tests, full-blood cell count and hepatic function tests
      performed in 2 months intervals in the course of treatment. RESULTS: Fifty of the
      patients were female and 15 were male with a mean age of 47.0+/-16.9 (17-80). A
      total number of 106 cysts were present in 65 patients. Mean cystic diameter was
      5.5+/-3.6 (1-16). In 41 of the patients, cysts were solitary and in remaining 24
      patients cysts were multiple. Mean follow-up period was 28.3+/-8.6 (12-42)
      months. The overall success rate of albendazole therapy was 18% (12/65) in the
      study. CONCLUSION: Albendazole therapy for hepatic hydatidosis is not effective
      in the vast majority of patients and, therefore, should not be used as the
      primary therapy for patients who are surgical candidates.

PMID- 18085342
TI  - Outcome of surgical treatment of hilar cholangiocarcinoma.
AB  - To evaluate surgical results and the effect of adjuvant chemotherapy in cases of
      hilar cholangiocarcinoma, we retrospectively analyzed 27 consecutive patients who
      underwent surgical resection (eight bile duct resections, 18 bile duct resections
      plus hepatectomy, one hepatopancreaticoduodenectomy). There was no operative
      mortality, and the morbidity was 37%. Curative resection (R0 resection) was
      achieved in 20 (74%) patients. Overall survival at 3 and 5 years was 44% and 27%,
      significantly higher than that of 47 patients who did not undergo resection (3.5%
      and 0% at 3 and 5 years, p < 0.0001). Survival of patients with positive margins
      (R1/2 resection) was poor; there were no 5-year survivors. However, survival was
      better than that of patients who did not undergo resection (median survival: 22
      vs 9 months, p = 0.0007). Univariate analysis identified lymph node metastasis as
      a negative prognostic factor (p = 0.043). Median survival of patients who
      underwent adjuvant chemotherapy was significantly longer than that of patients
      who did not (42 vs. 22 months, p = 0.0428). Resection should be considered as the
      first option for hilar cholangiocarcinoma. There appears to be a survival
      advantage even in patients with cancer-positive margins. Adjuvant chemotherapy
      may increase long-term survival.

PMID- 18085343
TI  - The role of extended lymphadenectomy for adenocarcinoma of the head of the
      pancreas: strength of the evidence.
AB  - With improvements in the safety of Whipple resection in recent decades, surgeons
      have continued to explore the role of more extensive lymphadenectomy in hope of
      improving long-term survival. A systematic literature search of level I evidence
      addressing the role of the extent of lymphadenectomy was undertaken. Only reports
      of prospective, randomized controlled trials comparing pancreaticoduodenectomy
      with standard lymphadenectomy to pancreaticoduodenectomy with extended
      lymphadenectomy where information regarding survival, morbidity, mortality, the
      number of resected lymph nodes in each group and detailed operative technique
      were included. Four prospective, randomized trials comprising some 424 patients
      and one meta-analysis were identified. In aggregate, these studies confirmed that
      the number of resected lymph nodes was significantly higher in the
      pancreaticoduodenectomy with extended lymphadenectomy group. Morbidity and
      mortality rates were comparable. Postoperative diarrhea in the early months after
      operation was problematic in patients undergoing extended lymphadenectomy. In
      none of the studies was a benefit in long-term survival demonstrated. Standard
      pancreaticoduodenectomy continues to be the operation of choice for
      adenocarcinoma of the head of the pancreas.

PMID- 18085344
TI  - Perioperative morbidity affects long-term survival in patients following liver
      resection for colorectal metastases.
AB  - BACKGROUND: Hepatic resection is the treatment of choice in patients with
      colorectal liver metastases. Perioperative morbidity is associated with decreased
      long-term survival in several cancers. The aim of this study was to assess the
      impact of perioperative morbidity and other prognostic factors on the outcome of
      patients undergoing liver resection for colorectal metastases. METHODS: One
      hundred ninety seven patients undergoing liver resection with curative intent
      were investigated. The influence of prognostic factors, such as complications,
      tumor stage, margins, age, sex, number of lesions, transfusion, portal inflow
      obstruction, and era and type of resection, was assessed using univariate and
      multivariate analysis. Complications were graded using an objective surgical
      complication classification. RESULTS: The 5-year survival rate was 38%, with a
      median follow up of 4.5 years. The disease-free survival rate at 5 years was 23%.
      The perioperative morbidity and mortality rates were 30 and 2.5%, respectively.
      The median survival of patients with perioperative complications was 3.2 years,
      compared to 4.4 years in those patients without complications (p < 0.01). For
      patients with positive resection margins, the median survival was 2.1 years,
      compared 4.4 years in patients with a margin (p = 0.019). CONCLUSION:
      Perioperative morbidity and a positive resection margin had a negative impact on
      long-term survival in patients following liver resection for colorectal
      metastases.

PMID- 18085345
TI  - Psychosocial status in adolescents undergoing bariatric surgery.
AB  - BACKGROUND: Little is known about the psychosocial status of adolescents who
      undergo bariatric surgery. Our objective was to describe the psychological and
      behavioral characteristics of patients in this age group who underwent bariatric
      surgery at our institution. METHODS: A review of clinical charts of patients aged
      14-21 years who had bariatric surgery at our institution between 2000 and 2005
      was conducted. Abstracted data included clinical information and the results of a
      psychosocial evaluation consisting of a clinical interview with a psychologist
      and self-reported data from the Weight and Lifestyle Inventory and the Beck
      Depression Inventory-II. RESULTS: Twenty-five patient records were reviewed.
      Nineteen patients (76%) were female. The mean (+/-SD) age was 18.7 +/- 1.6 years,
      and mean body mass index was 50.6 +/- 7.9 kg/m(2). Depression was the most common
      psychiatric comorbidity (68%). Abnormal eating behaviors were frequent and
      included binge eating (48%), rapid eating (44%), having guilt associated with
      eating (36%), eating until uncomfortably full (36%), loss of control (24%),
      eating without hunger (24%), and eating alone (20%). Sixteen patients were judged
      to be appropriate for surgery by the bariatric surgery team; surgery was delayed
      for nine patients primarily because of concerns about ability to adhere to the
      postoperative diet. These patients were recommended for additional dietary
      counseling and/or psychotherapeutic treatment prior to surgery. CONCLUSIONS:
      Among adolescent bariatric surgery candidates, depression and aberrant eating
      behaviors were very common. Early identification and management of these
      conditions may enable most of these patients to undergo bariatric surgery and
      optimize the likelihood for a successful outcome.

PMID- 18085346
TI  - Indications for incisional hernia repair: an international questionnaire among
      hernia surgeons.
AB  - BACKGROUND: Incisional hernia repair can be a significant challenge for both
      surgeon and patient. Despite the growing amount of literature describing various
      methods of surgical techniques, little has been published regarding the natural
      course of incisional hernia and the opinions about indications for incisional
      hernia repair. METHODS: A questionnaire was sent to a group of surgeons
      internationally renowned in incisional hernia surgery and research. RESULTS: Pain
      and limitations of daily activities were considered the most important
      indications for repair. Cosmetic complaints were seen as least important. About
      23% of patients were asymptomatic. More than 20% did not receive surgical
      treatment. CONCLUSIONS: A large proportion of patients with incisional hernia is
      not operated. Despite this large group of patients, valid data describing the
      natural course are absent. A prospective trial monitoring incisional untreated
      hernias as well as comparing conservative treatment with repair should be
      performed.

PMID- 18085347
TI  - Laparoscopic resorbable mesh fixation. Assessment of an innovative disposable
      instrument delivering resorbable fixation devices: I-Clip(TM). Final results of a
      prospective multicentre clinical trial.
AB  - BACKGROUND: The aim of this study was to assess the performance and tolerance of
      an innovative disposable instrument delivering resorbable clips (I-Clip,
      Sofradim, France) intended for mesh fixation in inguinal, incisional and
      umbilical hernias of the abdominal wall. The fixation device was designed to be
      resorbable in 1 year, with reduced trauma to the underlying tissues or the mesh,
      and with initial mechanical properties equivalent to those of conventional metal
      staples. METHODS: The study involved 105 patients with inguinal, umbilical or
      incisional hernias enrolled from 11 centres. Inguinal totally extra peritoneal
      (TEP) or trans abdomino pre-peritoneal (TAPP) repair was performed with Parietex
      mesh, incisional or umbilical hernias were treated via the intraperitoneal route
      with Parietex composite. I-Clips were used for mesh fixation in both indications
      according to the surgeon's habits. Efficacy was the principal assessment criteria
      evaluated by two parameters: quality of fixation evaluated subjectively at the
      time of procedure and recurrence rate according to the follow up at 1, 6 and 12
      months. Pain evaluated by the patients using a visual analogue scale (VAS) was
      the principal secondary assessment criteria. Other tolerance criteria were also
      evaluated during surgery and follow up. RESULTS: The surgeons' evaluation of the
      fixation quality was assessed as good to very good in 100% of ventral hernias and
      good to very good in 85-92% of inguinal hernias. At 1 month, 90% of patients
      (94/104) were totally pain-free (VAS score: 0) and only ten patients reported low
      pain (VAS scores: 0.3-3.1). At 1 year, the pain described by those ten patients
      finally disappeared, 98% of patients (102/104) were totally pain-free. The rate
      of minor complications not related to the device concerned 5% of the patients at
      1 month, which was reduced to 2% at one year and no recurrence or mesh sepsis was
      observed. CONCLUSIONS: The ease of use of this device, combined with the absence
      of recurrence related to the investigated device and the good pain-free outcome
      in this group of patients confirmed the effectiveness and tolerance of the
      resorbable fixation concept of I-Clip(TM).

PMID- 18085348
TI  - Current status and future clinical applications of lymphatic mapping in
      gastrointestinal cancer.

PMID- 18085349
TI  - Clinicopathologic features and histochemical analyses of proliferative activity
      and angiogenesis in small cell carcinoma of the esophagus.
AB  - BACKGROUND: We investigated clinicopathologic features in patients with
      esophageal small cell carcinoma (SCEC), and its proliferative activity and
      angiogenesis. METHODS: Ten patients with SCEC from 335 esophageal carcinoma
      patients were analyzed clinicopathologically. For analyses of cell proliferation,
      apoptosis, and angiogenesis of SCEC, Ki-67 immunostaining, the TUNEL method, and
      CD31 and CD68 immunostaining were used. RESULTS: Esophagectomy was performed in
      nine patients, while one with extensive SCEC was treated by repeated chemotherapy
      and radiotherapy. Four patients received chemotherapy both before and after
      surgery, one only before surgery, and four only after surgery. Cisplatin and
      etoposide were given to five patients, while irinotecan and cisplatin were given
      to three. Five survived more than 18 months, and two more than 36 months. One of
      these two had limited SCEC treated by surgery and chemotherapy, whereas the other
      had extended SCEC treated by repeated chemotherapy and radiotherapy. The
      microvessel count and the Ki-67 labeling index of SCEC were higher than those of
      squamous cell carcinoma (P = 0.0033 and P = 0.0005, respectively). Between SCEC
      with and without preoperative chemotherapy, the Ki-67 labeling index was lower (P
      = 0.027) and the apoptotic index was higher in the treated SCEC (P = 0.014).
      Between SCEC patients who survived more or less than 18 months, the microvessel
      count was lower in those who survived more than 18 months (P = 0.049).
      CONCLUSIONS: Esophagectomy may be indicated for limited SCEC combined with
      chemotherapy. SCEC has high proliferative activity and rich neovascularization,
      and its proliferative activity may be suppressed by chemotherapy.

PMID- 18085350
TI  - Cellular membrane fluidity measurement by fluorescence polarization in
      indomethacin-induced gastric cellular injury in vitro.
AB  - BACKGROUND: Gastric complications of indomethacin involve generation of reactive
      oxygen species, which induce gastric mucosal injury via lipid peroxidation of
      cell membranes. Peroxidation by reactive oxygen species alters the amounts of
      unsaturated fatty acids in the cell membrane and thus affects membrane fluidity.
      Indomethacin-induced lipid peroxidation can thus be detected by measuring
      cellular membrane fluidity by the fluorescence polarization (FP) method. The aim
      of this study was to elucidate the usefulness of the FP method for detecting
      indomethacin-induced gastric cellular injury in RGM-1 cells. METHODS:
      Indomethacin-treated RGM-1 cells were investigated by conventional cytotoxicity
      assay, fluorometry of diphenyl-1-pyrenylphosphine (DPPP) to detect lipid
      peroxidation, and FP. The effects of both a radical scavenger and an initiator on
      membrane fluidity change (MFC) in RGM-1 cells were examined. The sensitivity of
      FP in detecting cellular injury was compared with those of DPPP fluorometry and
      conventional cytotoxicity measurements. RESULTS: Indomethacin caused an increase
      in MFC as determined by FP before cytotoxicity was detected by conventional
      methods. The increase in MFC was associated with increased membrane phospholipid
      peroxidation (MPP) but not with a prostaglandin deficiency, and the increases in
      both MFC and MPP were prevented by vitamin E. CONCLUSIONS: The FP method is
      potentially useful for detecting cellular injury in vitro.

PMID- 18085351
TI  - The production of interferon-gamma-inducible protein 10 by granulocytes and
      monocytes is associated with ulcerative colitis disease activity.
AB  - BACKGROUND: To clarify which types of cells produce interferon-gamma-inducible
      protein 10 (IP-10) and whether IP-10 is associated with the development of
      ulcerative colitis (UC), we investigated IP-10 production in UC patients.
      METHODS: Serum IP-10 levels were measured using enzyme-linked immunosorbent assay
      in 29 patients with active and 21 with inactive UC and in 20 controls. The
      production of IP-10 by granulocytes and monocytes adsorbed to G-1 beads was
      examined. In 21 active UC patients treated with granulocyte and
      monocyte/macrophage adsorptive apheresis (GMA), serum IP-10 levels were measured
      before and after treatment. IP-10-positive cells in UC mucosa were also examined
      immunohistochemically using tissues obtained by surgical resection and
      colonoscopic biopsies. RESULTS: Serum IP-10 levels in active UC patients were
      significantly higher than those in inactive patients, although even in the latter
      the levels were increased compared with those in controls. IP-10 production by
      granulocytes and monocytes in active UC patients was significantly higher than
      that in controls. Furthermore, the number of IP-10-positive cells was elevated in
      the colonic mucosa of patients with active UC, and one of the main subpopulations
      of IP-10-positive cells was granulocytes. Serum IP-10 levels decreased following
      GMA treatment in responders, but not in nonresponders. Interestingly, serum IP-10
      levels before GMA were higher in responders than in nonresponders. In parallel
      with the serum levels, IP-10-positive cells also decreased following GMA
      treatment. CONCLUSIONS: Serum IP-10 levels reflected UC disease activity, and the
      source of IP-10 was granulocytes and monocytes. Furthermore, serum IP-10 levels
      may be a marker for the responsiveness of patients to GMA treatment.

PMID- 18085352
TI  - Clinicopathological study on the intraductal spread of small pancreatic cancer.
AB  - BACKGROUND: The aim of this study was to evaluate histopathologically the
      frequency, direction, and length of intraductal spread (IS) along the main
      pancreatic duct from the main tumor of small pancreatic cancer. METHODS: Resected
      specimens from 20 cases of pTS1 (histologically 2 cm or less in diameter)
      pancreatic cancer (September 1983 to December 2005) were examined
      histopathologically. As controls, 40 resected specimens from cases of pTS2 (more
      than 2 cm and less than 4 cm in diameter) or larger sized pancreatic cancer
      (pTS2<or=) were examined in the same manner. The specimens were evaluated
      histopathologically as to (1) the prevalence of IS, (2) the direction and length
      of IS, and (3) the positive rates of transpapillary cytology of pure pancreatic
      juice (TPC) and biopsy of the main pancreatic duct (TPB), performed
      preoperatively. RESULTS: IS was observed in 45% of pTS1 and 13% of pTS2<or=
      cases. In 88% of cases of pTS1, IS was observed in the direction of the ampullary
      side. In 40% of cases of pTS2<or=, IS toward the ampullary side was seen. The
      mean length of IS in pTS1 and pTS2<or= cases was 11.8 mm and 7.2 mm,
      respectively. Positive rates of TPC and TPB in pTS1 cases were 70% and 75%,
      respectively, and in pTS2<or= cases, 50% and 44%, respectively. CONCLUSIONS: The
      frequency of IS was high in pTS1 cases, which suggests there is potential for
      improvement in establishing the histocytological diagnosis of small pancreatic
      cancer via the transpapillary approach with the development of adequate tools.

PMID- 18085353
TI  - Lens culinaris agglutinin-reactive alpha-fetoprotein and protein induced by
      vitamin K absence II are potential indicators of a poor prognosis: a
      histopathological study of surgically resected hepatocellular carcinoma.
AB  - BACKGROUND: We histopathologically examined Lens culinaris agglutinin-reactive
      alpha-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) and protein
      induced by vitamin K absence (PIVKA) II-positive HCC to clarify the efficacy of
      these markers for predicting a poor prognosis. METHODS: Serum AFP-L3 and PIVKA II
      was measured in 110 HCC patients. AFP-L3 was measured by lectin-affinity
      electrophoresis coupled with antibody-affinity blotting, and PIVKA II by using a
      high-sensitivity kit. The growth type, capsule formation, capsule infiltration,
      portal vein invasion, intrahepatic metastasis and histological tumor grade were
      evaluated pathologically. RESULTS: Thirty-eight (35%) HCC patients were AFP-L3
      positive, and 63 (57%) were PIVKA II-positive. In AFP-L3-positive HCC, the
      frequencies of an infiltrative growth type (positive : negative = 66% : 42%, P =
      0.027) and a poorly differentiated type (positive : negative = 32% : 6%, P <
      0.001) were significantly higher than in AFP-L3-negative HCC. In PIVKA II
      positive HCC, the frequencies of an infiltrative growth type (positive : negative
      = 62% : 28%, P < 0.001), vascular invasion (positive : negative = 63% : 26%, P <
      0.001), and intrahepatic metastasis (positive : negative = 38% : 4%, P < 0.001)
      were significantly higher than in PIVKA II-negative HCC. In both AFP-L3- and
      PIVKA II-positive HCC, the frequency of a poorly differentiated growth type was
      significantly higher than in HCC positive for either AFP-L3 or PIVKA II or HCC
      negative for both AFP-L3 and PIVKA II (both positive : either positive : both
      negative = 37% : 12% : 0%; P = 0.014, P < 0.001, respectively). CONCLUSIONS: AFP
      L3 was related to progression from moderately differentiated to poorly
      differentiated HCC, whereas PIVKA II was more specific to vascular invasion.
      PIVKA II is therefore likely to be a useful indicator of vascular invasion.

PMID- 18085354
TI  - Lipopolysaccharide induces adipose differentiation-related protein expression and
      lipid accumulation in the liver through inhibition of fatty acid oxidation in
      mice.
AB  - BACKGROUND: In the present study, we examined the effect of lipopolysaccharide
      (LPS) on liver histopathology with special reference to lipid metabolism in mice.
      METHODS: Mice were injected with LPS intraperitoneally, and its effect on the
      liver was investigated pathologically and biochemically. RESULTS: Oil-red O
      staining and adipose differentiation-related protein (ADRP) immunohistochemistry
      demonstrated that injection of LPS transiently induced lipid accumulation and
      ADRP expression in hepatocytes, especially around the portal vein. Microscopic
      observation revealed that lipid accumulation started 12 h after LPS injection.
      Time-course studies showed that LPS rapidly, within 2 h, decreased hepatic
      expression of nuclear hormone receptors, including peroxisome proliferator
      activated receptor (PPAR) alpha. LPS inhibited the expression of PPARalpha-target
      genes involved in fatty acid oxidation in the liver such as those coding for
      enoyl-CoA hydratase, acyl-CoA dehydrogenase, and carnitine palmitoyl transferase
      1, whereas LPS also suppressed the expression of genes related to fatty acid
      synthesis such as those for fatty acid synthase, stearoyl-CoA desaturase, and
      acetyl-CoA carboxylase alpha. CONCLUSIONS: LPS induces transient lipid
      accumulation and expression of ADRP in the liver through inhibition of fatty acid
      oxidation by downregulation of the PPARalpha-related transcriptional mechanism.

PMID- 18085355
TI  - Cervical mediastinoscopy versus computed tomography for detecting enlarged
      mediastinal lymph nodes in non-cancerous lung diseases.
AB  - Cervical mediastinoscopy (CM) is considered to be the gold standard for
      evaluating mediastinal lymph nodes. The aim of this study was to determine the
      diagnostic yield of computed tomography (CT) and CM for detecting enlarged
      mediastinal lymph nodes in non-malignant pulmonary diseases. We retrospectively
      investigated the correlation and differentiation between chest CT and CM findings
      in terms of sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV), in 30 patients with granulomatous lung disease
      diagnosed by CM and isolated enlarged lymph nodes seen on CT scans. Biopsy
      tissues from the lymph nodes in stations right, 1, 2, 3, 4, and 7, were obtained
      for pathological examination. The 30 patients comprised 11 men (mean age 47.1 +/-
      18.4 years) and 19 women (mean age 44.2 +/- 14.0 years). Radiological examination
      showed that the diagnostic value of stations 2 and 4 was particularly high. Thus,
      when CM is used for diagnostic purposes, the small lymph nodes in station 1,
      obtained by careful dissection of the higher mediastinal region, can be helpful.
      Generally, there is no absolute consistency between the findings of CM and CT.
      For this reason, obtaining samples from each station regardless of CT findings is
      recommended.

PMID- 18085356
TI  - Abdominal compartment syndrome.
AB  - Compartment syndrome is a pathophysiological term, comprising a variety of
      tissues and organ alterations, due to a higher than normal pressure in an
      anatomically detached space (compartment). In the human body, areas denoted as
      compartments include the orbital globe, the sub and epidural space, the abdomen,
      pleura, pericardium, and others. Compartment syndrome was described initially in
      limbs. Abdominal compartment syndrome is defined as an intra-abdominal pressure
      above 20 mmHg with evidence of organ failure. Abdominal compartment syndrome
      develops when the intra-abdominal pressure rapidly reaches certain pathological
      values, within several hours (intra-abdominal hypertension is observed), and
      lasts for 6 or more hours. The key to recognizing abdominal compartment syndrome
      is the demonstration of elevated intra-abdominal pressure which is performed most
      often via the urinary bladder, and it is considered to be the "gold standard."
      Multiorgan failure includes damage to the cardiac, pulmonary, renal,
      neurological, gastrointestinal, abdominal wall, and ophthalmic systems. The gut
      is the most sensitive to intra-abdominal hypertension, and it develops evidence
      of end-organ damage before alterations are observed in other systems. The
      surgical decompression of the abdomen remains the treatment of choice of
      abdominal compartment syndrome; this usually improves the organ changes, and is
      followed by one of the temporary abdominal closure techniques in order to prevent
      secondary intra-abdominal hypertension.

PMID- 18085357
TI  - Prevalence of synchronous colorectal neoplasms detected by colonoscopy in
      patients with gastric cancer.
AB  - PURPOSE: Our purpose was to study the characteristics of colorectal neoplasms in
      patients with gastric cancer (GC). METHODS: The study group comprised GC patients
      who underwent colonoscopy before resection of their GC. We examined the
      prevalence, site, and histology of colorectal neoplasms, as well as the
      clinicopathological features and treatment of the patients who had synchronous
      colorectal cancers (CRC). The logistic regression model was applied to
      investigate the features of the GC patients with concurrent CRC. RESULTS: We
      studied 466 GC patients (mean age 64.5 years; 147 women, 319 men), 143 (31%) of
      whom had a family history of gastrointestinal cancer. Synchronous colorectal
      adenoma and cancer were detected in 182 (39%) and 18 (4%) patients, respectively.
      Among the 18 synchronous CRCs, 11 were in the early stages and 10 of these were
      resected endoscopically. The other eight required simultaneous open radical
      surgery. All the GC patients with synchronous CRC were older than 50 years.
      Statistical analysis did not show a significant difference between the features
      of the patients with and those without concurrent CRC. CONCLUSIONS: The
      possibility of synchronous colorectal neoplasms in GC patients cannot be
      disregarded in clinical practice; however, screening of the large bowel may not
      be necessary in GC patients younger than 50 years.

PMID- 18085358
TI  - Liver transplantation for cystic fibrosis in adults.
AB  - PURPOSE: To expand our knowledge on liver transplantation for cirrhosis
      associated with cystic fibrosis in adults. METHODS: Five patients who underwent a
      liver transplantation due to cystic fibrosis were reviewed. The outcome of the
      patients in terms of age, immunosuppression regimen, patient and graft survival,
      and pre- and post-transplant complications were investigated. RESULTS: Five adult
      liver transplant patients had cystic fibrosis (0.2%). These included 4 men and 1
      woman with a mean age of 31 +/- 10, ranging from 22 to 52 years old at the time
      of transplantation. All patients had lung problems. Four patients had exocrine
      and two had endocrine pancreatic insufficiency. Two are currently alive with a
      follow-up of 5.8 years and 4 months after transplantation, respectively. There
      were three deaths from pulmonary embolism at 4.5 years, myocardial infarction
      with cyclosporine nephrotoxicity at 10.7 years, and lymphoproliferative disorder
      at 5 months after transplantation. No deaths occurred from lung infection. Only
      one patient had postoperative pulmonary infectious complications, which were
      successfully treated with antibiotics and did not result in mortality.
      CONCLUSION: Adult liver transplantation for end-stage liver disease associated
      with cystic fibrosis offers encouraging results with a rapid general improvement
      after surgery and it is now considered to be a safe and acceptable treatment for
      this disease population.

PMID- 18085359
TI  - The effect of Nomega-nitro-L-arginine methyl ester and L-arginine on lung injury
      induced by abdominal aortic occlusion-reperfusion.
AB  - PURPOSE: The aim of this study was to examine the effects of Nomega-nitro-L
      arginine methyl ester (L-NAME) and L-arginine on lung injury after aortic
      ischemia-reperfusion (IR). METHODS: Twenty-four Wistar-Albino rats were
      randomized into four groups (n = 6) as follows: Control (sham laparotomy), Aortic
      IR (30 min ischemia and 120 min reperfusion), L-Arginine (intraperitoneal 100 mg
      kg(-1) live weight)+aortic IR, and L: -NAME (intraperitoneal 10 mg kg(-1) live
      weight)+aortic IR. In the lung specimens, the tissue levels of malondialdehyde
      (MDA), vascular endothelial growth factor (VEGF), and nitric oxide (NO) were
      measured and a histological examination was done. RESULTS: Aortic IR increased
      MDA, VEGF, and NO. L-Arginine further significantly increased MDA and NO, and
      decreased VEGF (P < 0.05 vs aortic IR). L-NAME significantly decreased MDA and NO
      (P < 0.05 vs L-arginine+aortic IR) and increased VEGF (P < 0.05 vs other groups).
      A histological examination showed the aortic IR to significantly increase (P <
      0.05 vs control) while L-arginine also further increased (P > 0.05 vs aortic IR),
      whereas L-NAME caused a significant decrease in pulmonary leukocyte infiltration
      (P < 0.05 vs aortic IR). CONCLUSIONS: Our results indicate that L-arginine
      aggravates the lung injury induced by aortic IR, while L-NAME attenuates it.

PMID- 18085360
TI  - Effect of FTY720 and ex vivo graft irradiation in rat small bowel
      transplantation: expression of mucosal addressin cell adhesion molecule-1.
AB  - PURPOSE: We performed a semiquantitative analysis of the expression of Mucosal
      addressin cell adhesion molecule-1 (MAdCAM-1) and gut-associated tissues (GALT)
      during small bowel graft rejection in the rat to confirm the effect of FTY720 and
      ex vivo graft irradiation. METHODS: Small bowel transplantations (SBT) were
      performed from BN rats to LEW rats. Four groups of SBT animals were studied on
      days 3, 5, and 7 after operations (untreated, FTY720, ex vivo graft irradiation,
      FTY720+ex vivo graft irradiation). Indirect immunoperoxidase staining was
      performed against CD4 and MAdCAM-1. The number of CD4-positive cells in the
      allografts was also analyzed by flow cytometry. RESULTS: The graft survival was
      prolonged only in the FTY720-treated groups. The SBT allografts treated by FTY720
      demonstrated less infiltration, but the ex vivo graft irradiation group did not
      show any effect on its expression. In the FTY720-treated groups, MAdCAM-1
      expression on high endothelial venules (HEVs) in Peyer's patches (PPs) was
      upregulated and its expression on endothelial cells of vessels in the lamina
      propria was downregulated in comparison with the allograft group without FTY720.
      CONCLUSIONS: It is important to prevent the infiltration of CD4-positive cells,
      the downregulation of MAdCAM-1 expression on HEVs in PPs and the upregulation of
      MAdCAM-1 expression on endothelial cells of vessels in the lamina propria for the
      prolongation of graft survival.

PMID- 18085361
TI  - Ductal carcinoma in situ arising in a benign phyllodes tumor: report of a case.
AB  - Malignant epithelial change within a phyllodes tumor (PT) is a rare event. To our
      knowledge, only six cases of ductal carcinoma in situ arising in a PT have been
      reported in English. We report a case of PT with an intraductal carcinoma
      component, which grew rapidly to a huge size in 3 months. Histologically, the
      stromal element showed mild to moderate cellularity with few mitoses and mild
      nuclear atypia. The epithelial element consisted of irregularly dilated ducts
      with a phyllodes structure that had moderate to severe epithelial hyperplasia,
      and foci of cribriform ductal carcinoma in situ with comedo necrosis.

PMID- 18085362
TI  - A solitary metastatic lung tumor from thyroid papillary carcinoma diagnosed by
      endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA):
      report of a case.
AB  - A solitary metastatic tumor from thyroid papillary carcinoma is rarely diagnosed
      preoperatively. A 61-year-old woman was referred to us for investigation of a
      solitary nodule in the right lung field on a chest X-ray, several years after a
      right hemithyroidectomy for thyroid carcinoma. Endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) of a tumor in the right lower lobe,
      adjacent to the inferior pulmonary vein, revealed metastasis of thyroid papillary
      carcinoma. Immunohistochemical examination of histological cores obtained from
      the EBUS-TBNA proved extremely helpful in confirming the diagnosis. We performed
      right lower lobectomy with lymph node sampling, and the final pathological
      diagnosis was papillary carcinoma without lymph node metastasis.

PMID- 18085363
TI  - Airlessness in airspace. Simultaneous occurrence of spontaneous pneumothorax with
      pneumomediastinum and pneumorrhachis: report of a case.
AB  - Spontaneous pneumothorax and pneumomediastinum is an uncommon condition and its
      association with pneumorrhachis (air inside the spinal canal) is even more
      unusual. An early diagnosis is lifesaving for this potentially fatal condition.
      We herein present the multidetector computed tomography features of a patient
      with pneumorrhachis with spontaneous pneumothorax and pneumomediastinum.

PMID- 18085364
TI  - Multilocular mediastinal cyst with rim calcification: report of a case.
AB  - We report a case of a multilocular anterior mediastinal cyst with rim
      calcification and severe adhesion to the adjacent organs. We excised the cyst
      completely, with resection of the left phrenic nerve, pericardium, and left lung
      because of the severe adhesion. Histological examination revealed that the
      multilocular cystic walls were composed of fibrous connective tissue and
      calcifications, but the lining epithelial cells were absent because of dystrophic
      calcification resulting from chronic inflammation. On the basis of the location
      and pathological findings, we diagnosed a multilocular mediastinal cystic tumor;
      most likely a multilocular thymic cyst. It is important to distinguish a
      multilocular thymic cyst from a unilocular thymic cyst because a multilocular
      thymic cyst may recur postoperatively and coexist with a thymic epithelial tumor.
      Dense adhesion to the surrounding mediastinal structures may make removal
      difficult, especially if there is rim calcification.

PMID- 18085365
TI  - Late-onset chylothorax after blunt chest trauma at an interval of 20 years:
      report of a case.
AB  - We herein report an extremely rare case of a patient chylothorax at an interval
      of 20 years after thoracic vertebrae fractures, who underwent a successful
      thoracoscopic thoracic duct ligation and pleurodesis. A 51-year-old man was
      referred to our hospital with shortness of breath on effort about 1 month after
      participating in archery. Twenty years previously, he was involved in a traffic
      accident. At that time, the patient sustained trauma to the spine and suffered a
      spinal injury, thus resulting in paralysis in the lower part of his body. A chest
      roentgenogram and computed tomogram revealed a large amount of bilateral pleural
      effusion. After thoracentesis was performed, a diagnosis of chylothorax was made
      and the patient was hospitalized. Conservative management by a low-fat diet
      proved to be unsuccessful. The patient did not request pleurodesis, because
      pleural adhesions might impair pulmonary function. As a result, we decided to
      perform surgery. On the right side, we performed video-assisted thoracoscopic
      surgery by clipping the thoracic duct and applying an absorbable sealing
      material. Thereafter, pleurodesis was performed and OK-432 was instilled.
      Thereafter, the pleural fluid flow was almost completely stopped. On the left
      side, pleurodesis was effective. The patient has since remained symptom free and
      has been followed up on an outpatient basis for 9 months after the 100th
      postoperative day. We assumed that the chylothorax in this case was related to
      the earlier traffic accident.

PMID- 18085366
TI  - Emergency pulmonary embolectomy during the second trimester of pregnancy: report
      of a case.
AB  - We report a case of acute massive pulmonary thromboembolism, which occurred
      during the second trimester of pregnancy in a 35-year-old woman with
      thrombocytopenia and anemia secondary to myelodysplastic syndrome. We performed
      successful emergency pulmonary embolectomy, under cardiopulmonary bypass, using
      argatroban as an anticoagulant. An intra-aortic balloon pump was used to maintain
      placental blood flow. The patient recovered completely and was later delivered of
      a healthy baby. Thus, pulmonary embolectomy saved both the mother and the fetus.

PMID- 18085367
TI  - Surgical treatment of an aortoesophageal fistula caused by stent implantation for
      esophageal stenosis: report of a case.
AB  - An aortoesophageal fistula is uncommon, but almost always fatal. We report a case
      of an aortoesophageal fistula that developed after stent dilation for an
      esophageal stricture caused by benign esophagitis. As soon as esophageal
      hemorrhaging was identified by endoscopy, the patient was transferred to the
      operating theater; however, the uncontrollable and massive bleeding resulted in
      pulseless shock. The digestive surgeon put side-clamps on the descending aorta
      and esophagus and transferred the patient to our hospital. We identified an
      aortoesophageal fistula, 3.0 mm in diameter, in the descending aorta, and
      performed a graft replacement of the descending aorta and esophagectomy. It was
      immediately evident that the edge of the stent had been sticking into the aortic
      wall, which had caused the fistula. To our knowledge, this is the first report of
      successful surgical treatment of an aortoesophageal fistula caused by esophageal
      stent dilatation.

PMID- 18085368
TI  - Secondary c-kit mutation in a recurrent gastrointestinal stromal tumor under long
      term treatment with imatinib mesylate: report of a case.
AB  - Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of
      the c-kit receptor gene, which are targets for imatinib mesylate. However,
      imatinib resistance is an increasing clinical problem. We herein present such a
      case with a recurrent GIST, in association with the development of a secondary
      mutation in the c-kit gene. A 67-year-old man, who had a GIST of the stomach with
      multiple liver metastases, underwent a partial gastrectomy, distal
      pancreatectomy, and partial hepatectomy. After surgery, he was treated with
      imatinib. However, during the approximately 4-year treatment period, a recurrence
      of the GIST in the liver was detected, for which a partial hepatectomy was again
      performed. The primary GIST constitutively had a deletion mutation in exon 11. In
      addition, the recurrent hepatic tumor developed a secondary point mutation
      (Val654Ala) in exon 13, which may be responsible for the imatinib resistance.

PMID- 18085369
TI  - Lymphoepithelial cyst of the pancreas: report of a case.
AB  - A lymphoepithelial cyst (LEC) is an extremely rare benign lesion of the pancreas.
      During a medical check-up, a 77-year-old man without any symptoms was found to
      have a cyst in the body of the pancreas. His serum carbohydrate antigen 19-9
      level was slightly elevated. Computed tomography showed a multilocular, low
      attenuating cyst on the superior surface of the pancreatic body. Thus, we
      performed distal pancreatectomy with splenectomy. Histological examination
      revealed that the cyst wall was lined with squamous epithelium and surrounded by
      abundant mature lymphoid tissue. Keratinous substances were present in the cyst.
      An LEC of the pancreas is associated with a good prognosis and, although unusual,
      it should be considered in the differential diagnosis of pancreatic cystic
      lesions. Minimal resection of the cyst should be performed whenever possible, and
      extensive surgery avoided. For patients with a high surgical risk, fine-needle
      aspiration biopsy may be considered.

PMID- 18085370
TI  - Pancreatic angiomatosis: report of a case.
AB  - Recent advances in imaging techniques such as dynamic intravenous contrast
      enhanced computed tomography (CT) and magnetic resonance imaging (MRI) have
      enabled us to detect pancreatic cysts, some of which are potentially malignant.
      As the histopathological diagnosis cannot be confirmed preoperatively, enlarged
      pancreatic cysts are usually removed surgically. We report a rare case of
      pancreatic angiomatosis in a 21-year-old woman who presented with vague abdominal
      pain, a feeling of fullness, and nausea. Abdominal ultrasonography, contrast
      enhanced CT, and MRI showed a huge mass in the right upper abdomen. We performed
      pylorus-preserving pancreato-duodenectomy, and the histopathological examination
      of the excised specimen revealed that the tumor was angiomatosis, probably
      originating from parapancreatic fibro-adipose tissue. She is doing well and has
      no evidence of recurrence 8 years after the operation. A complete surgical
      excision should be performed as curative treatment for pancreatic angiomatosis,
      which is an extremely rare disease when not associated with Von Hippel-Lindau
      syndrome.

PMID- 18085371
TI  - Diffuse large B-cell lymphoma in the ampulla of vater causing obstructive
      jaundice: report of a case.
AB  - We report a case of diffuse large B-cell lymphoma (DLBCL) in the ampulla of
      Vater, causing painless obstructive jaundice in a 78-year-old woman. Duodenal
      endoscopy revealed a mass in the ampulla of Vater and narrowing of the second
      portion of the duodenum, although diagnosing DLBCL from an endoscopic biopsy was
      impossible because there were several kinds of leukocytes in the infiltrate. We
      performed pylorus-preserving pancreatoduodenectomy to establish a histological
      diagnosis, relieve the obstructive jaundice, and remove the narrowed second
      portion of the duodenum. Histological and immunohistochemical examination of the
      surgically resected specimen confirmed a diagnosis of DLBCL. Chemotherapy is the
      mainstay of treatment for DLBCL; however, surgery still plays an important role
      when the histological diagnosis cannot be established preoperatively and when
      complications are not amenable to nonsurgical therapy.

PMID- 18085372
TI  - Cystic lymphangioma of the gallbladder: report of a case.
AB  - Abdominal lymphangioma is usually diagnosed within the first 2 years of life and
      is extremely rare in adults. The most common location of abdominal lymphangioma
      is the mesentery, but there are sporadic reports of its development in the
      gallbladder. A 66-year-old woman was found to have a cystic lesion near the
      gallbladder. Preoperative studies, including endoscopic ultrasonography, computed
      tomography, and magnetic resonance imaging, showed a tumor with multilocular
      cystic structure, originating in the gallbladder fossa. The patient underwent
      exploratory laparotomy, and the mass was resected en bloc with the gallbladder,
      as there was no evidence of malignancy on intraoperative ultrasonography.
      Macroscopically, the tumor was a multilocular cystic mass, 6 x 3 x 2 cm in size,
      with a rough, sponge-like appearance. Histologically, the cystic tumor was
      diagnosed as a lymphangioma, originating in the gallbladder. To our knowledge,
      only three other cases of a cystic lymphangioma originating in the gallbladder
      have been reported in the medical literature of the world.

PMID- 18085373
TI  - Adenomyomatous hyperplasia of the common bile duct: report of a case.
AB  - Adenomyomatous hyperplasia is most commonly found in the stomach, gallbladder,
      duodenum, and jejunum, while it is rarely found in the extrahepatic bile duct. A
      62-year-old woman was referred to our institution with a diagnosis of common bile
      duct (CBD) stenosis which had been detected by endoscopic retrograde
      cholangiopancreatography (ERCP). Abdominal computed tomography with contrast
      medium revealed a thickening of the wall of the lower CBD, and this lesion was
      weakly enhanced by contrast medium in the arterial phase. ERCP revealed a 15-mm
      long stenosis of the lower CBD, but no malignant cells were detected by either
      bile cytology or brush cytology. Because CBD cancer could not be ruled out,
      pylorus-preserving pancreatoduodenectomy was performed. Histopathologically,
      multiple hyperplastic glands without cellular atypia were present in the lower
      CBD wall. An immunohistochemical study showed fibroblasts with positive staining
      for alpha-smooth muscle actin surrounding the glands. The lesion was diagnosed to
      be adenomyomatous hyperplasia of the CBD. When a diagnosis of adenomyomatous
      hyperplasia of the CBD is difficult to make both preoperatively and
      intraoperatively, then a radical surgical procedure, such as a
      pancreatoduodenectomy, may be an effective treatment alternative.

PMID- 18085374
TI  - Kaposi's sarcoma after liver transplantation from a donor with a history of
      ventriculoperitoneal shunt and craniotomy for primary central nervous system
      lymphoma: report of a case.
AB  - The transplantation of organs from donors who have undergone shunt surgery or
      craniotomy for a malignant central nervous system (CNS) tumor is controversial.
      We report a case of Kaposi's sarcoma (KS) developing as a result of
      immunosuppression in the recipient of a liver transplant from a donor who
      underwent craniotomy and ventriculoperitoneal shunt surgery for primary CNS
      lymphoma. Polymerase chain reaction assay did not isolate human herpes virus-8 in
      the Kaposi lesions. To our knowledge, this is the only case ever reported of KS
      developing after liver transplantation from a donor with lymphoma. Thus, with
      appropriate screening to exclude possible dissemination, patients with a history
      of high-grade primary CNS lymphoma treated by ventriculoperitoneal shunt and
      craniotomy may be accepted as donors.

PMID- 18085375
TI  - Role of beta-defensins in oral epithelial health and disease.
AB  - The oral epithelium functions as a mechanical and protective barrier to resist
      bacterial infection. beta-Defensins are a group of antimicrobial peptides mainly
      produced by epithelial cells of many organs including skin, lung, kidney,
      pancreas, uterus, eye, and nasal and oral mucosa. This review focuses on beta
      defensins (BDs) in oral epithelia and discusses their importance in oral
      epithelial health and disease. BDs exhibit antimicrobial activity against oral
      microbes including periodontitis-related bacteria, Candida, and papilloma virus.
      Alterative expression of BDs was observed in oral epithelial diseases, including
      oral inflammatory lesions with and without microbial infection and oral cancer.
      BDs may be useful in the treatment of oral infectious diseases, ulcerative
      lesions, and cancer. BDs play an important role in protection against oral
      microbes and may be used in clinical applications.

PMID- 18085376
TI  - Molecular analysis of rat mammary carcinogenesis: an approach from carcinogenesis
      research to cancer prevention.
AB  - A rat strain carrying the human c-Ha-ras proto-oncogene is highly susceptible to
      chemically induced mammary carcinogenesis. All the transgenic rats develop
      preneoplastic mammary lesions within 20 days of an injection of N-methyl-N
      nitrosourea, and mammary carcinomas appear within 8 weeks of treatment with a
      variety of chemical carcinogens. In this review, we summarize molecular aspects
      of mammary carcinogenesis in transgenic rats and the potential application of
      this model for studies of breast cancer prevention.

PMID- 18085377
TI  - Neutralization of CXCL10 accelerates liver regeneration in carbon tetrachloride
      induced acute liver injury.
AB  - Remodeling of hepatic tissue structure following injury requires the coordinated
      action of hepatocytes, hepatic stellate cells (HSCs), and endothelial cells.
      However, their in vivo properties are not fully understood. We report here that
      the chemokine CXCL10 regulates hepatic tissue remodeling in a carbon
      tetrachloride (CCl(4))-induced acute liver injury in mice. The production of
      CXCL10 was enhanced by hepatocytes after CCl(4) exposure. Neutralization of
      CXCL10 protected mice from acute liver dysfunction and diminished hepatocellular
      loss. The hepatoprotective effect was associated with increased numbers of 5'
      bromo-2' deoxyuridine (BrdU)+ hepatocytes from day 1 and with accumulation of
      HSCs and endothelial cells within the injured zones from day 3. In vitro,
      recombinant CXCL10 directly inhibited the proliferation of hepatocytic cells,
      establishing a novel role of CXCL10 in modulating hepatocyte proliferation, in
      addition to a previously reported angiostatic role. In summary, neutralization of
      CXCL10 initially stimulates hepatocyte proliferation and, subsequently, HSC
      migration and angiogenesis to facilitate remodeling of hepatic cords. Thus,
      CXCL10 can be a novel therapeutic target for acute hepatocellular damage by
      regulating liver tissue remodeling.

PMID- 18085378
TI  - Immunohistochemical and immunoelectron microscopic studies of the localization of
      KL-6 and epithelial membrane antigen (EMA) in presumably normal pulmonary tissue
      and in interstitial pneumonia.
AB  - To clarify the localization of KL-6 and epithelial membrane antigen (EMA) in
      human lungs, immune reactions to antibodies to these factors were examined in
      detail at light and electron microscopic levels. Immunohistochemical
      investigation was performed in 17 cases of usual interstitial pneumonia (UIP),
      nonspecific interstitial pneumonia (NSIP), hypersensitivity pneumonitis (HP),
      collagen vascular disease-associated interstitial pneumonias (CVD-IP), viral
      pneumonia, and bronchobronchioloectasis, as well as in 10 cases of presumably
      normal pulmonary tissue resected as a result of spontaneous pneumothorax.
      Immunohistochemical study revealed similar discontinuous linear or dome-shaped
      positive patterns restricted to type II alveolar cells in presumably normal
      tissue and only some regions of interstitial pneumonia. In sharp contrast, immune
      reactions with each of the two antibodies yielded a continuous linear pattern
      surrounding damaged areas in most regions of interstitial pneumonias and some
      normal areas as well. Staining for EMA antibody was negative in some regenerating
      alveolar and bronchial cells in regenerating foci in interstitial pneumonias,
      although staining for KL-6 antibody was always positive in these cells.
      Immunoelectron microscopic studies demonstrated similar positive reactions with
      both antibodies on the surface of alveolar epithelial cells in three of the cases
      examined, with surface positive granules 100-200 nm in diameter. Thus, although
      staining for both KL-6 and EMA antibodies exhibited discontinuous positivity
      restricted to type II alveolar cells in nondamaged regions, immune reactions were
      continuous and linear in pattern in or around damaged areas of the lungs at both
      light and electron microscopic levels, probably as a consequence of cell-surface
      barrier function. These findings in pulmonary tissue might be evidence of defense
      functions.

PMID- 18085379
TI  - Expression pattern of p63 in oral epithelial lesions and submucous fibrosis
      associated with betel-quid chewing in Sri Lanka.
AB  - Betel-quid chewing, which is closely related to the high incidence of oral
      cancer, is prevalent in Sri Lanka. p63 has a remarkable structural similarity to
      p53, suggesting an aberrant expression in oral cancer. Using anti-p63 antibody
      and immunohistochemistry, the present study investigated the expression pattern
      of p63 in oral epithelial lesions, including different types of squamous cell
      carcinoma (SCC), different grades of epithelial dysplasia, and submucosal
      fibrosis associated with betel-quid chewing. Nuclear immunoreactivity for p63 was
      detected in all the cases, including normal oral epithelium and epithelial
      lesions. In normal oral epithelium, nuclear positivity for p63 was observed in
      some of the basal cell layers and focally in the parabasal layer. Nuclear
      positivity increased in the epithelial lesions. The percentage of positive nuclei
      in the epithelial lesions was significantly higher than in normal epithelium (P <
      0.01) and was also significantly higher in oral submucosal fibrosis than in
      epithelial dysplasia (P < 0.05). The results indicate that the overexpression of
      p63 in oral precancerous lesions and SCC in betel-quid chewers in Sri Lanka may
      be a useful marker for oral precancerous lesions.

PMID- 18085380
TI  - Distribution and role of myofibroblasts in human normal seminal vesicle stroma.
AB  - We studied the distribution of myofibroblasts in the stroma of normal seminal
      vesicles. Twelve normal seminal vesicles obtained by surgery on the diagnosis of
      some diseases were selected, and we evaluated the distribution of myofibroblasts
      in the seminal vesicles using immunohistochemical and electron and immunoelectron
      microscopic techniques. Immunohistochemically, myofibroblasts, which were
      positive for alpha-smooth muscle actin (ASMA) and negative for high molecular
      weight caldesmon (h-CD), were observed in the stroma just beneath the epithelium
      of normal seminal vesicles. Moreover, an electron microscope examination revealed
      the presence of spindle or stellate cells in the stroma of the lamina propria
      beneath the seminal vesicle epithelium, and an immunoelectron microscopic
      examination showed that these cells were positive for ASMA. Finally,
      myofibroblasts are distributed in the lamina propria of human normal seminal
      vesicles and may play an important role in the ejection of sperm plasm.

PMID- 18085381
TI  - Immunohistochemical phenotype of cutaneous cribriform carcinoma with a panel of
      15 antibodies.
AB  - We report a cribriform carcinoma of the left fossa poplitea in a 62-year-old
      woman. The patient did not present any symptoms, and the only complaint was the
      nodule, which was resected for diagnosis. After considering different diagnostic
      options, we decided that the most appropriate one was cribriform carcinoma, which
      is an entity described in 1998. The diagnostic criteria, which were provided in
      the few publications that refer to this entity, helped us to distinguish it from
      the main mimicker: cystic adenoid carcinoma. Owing to the cribriform pattern of
      the tumor, we also looked for a metastasis from other sites, mainly breast,
      vulva, and salivary glands, but all these were clinically excluded. The tumoral
      cells showed secretion by decapitation, as well as a positive stain of the
      luminal secretion by histochemical techniques of Alcian blue and periodic acid
      Schiff. The tumor was negative for iron stain. In spite of these characteristics,
      which are, for some authors, indicative of an apocrine phenotype, the
      immunohistochemical study revealed some differences with the profile that has
      been described in cases of apocrine adenocarcinoma. The tumor did not express
      GCDFP-15 or CD 15. It was also negative for SMA, CEA, and PR. The pattern of
      cytokeratins expressed by our case was positive for AE1-AE3, CAM 5.2, and CK7,
      without any expression for CK20. Other markers expressed by the tumor were EMA,
      ER, c-erbB-2, p53, and S-100.

PMID- 18085382
TI  - Large cell neuroendocrine carcinoma of the lung with calcification and expression
      of osteopontin.
AB  - A large cell neuroendocrine carcinoma (LCNEC) is a rare neoplasm. In this
      article, we report a case of LCNEC with stromal calcification. A 46-year-old
      Japanese man was found to have an abnormal shadow in the left upper lobe in a
      chest X-ray. As the size of the tumor increased during the follow-up, a left
      upper lobectomy was performed. Histological examination disclosed neuroendocrine
      morphology consisting of large cells, and subsequent immunohistochemistry
      confirmed the neuroendocrine differentiation. A diagnosis of LCNEC was
      established. Additionally, calcification was observed in the stroma within the
      tumor. Immunohistochemically, parts of neoplastic cells of LCNEC and calcified
      foci were positive for osteopontin. Finally, we suggest that osteopontin as well
      as dystrophy within the tumor may be involved in the stromal calcification of
      LCNEC.

PMID- 18085383
TI  - Immunohistochemical and electron microscopic studies of Langerhans cells in a
      case of multiple eccrine spiradenomas.
AB  - Multiple eccrine spiradenomas are rare. In the present study, a detailed
      investigation of eccrine spiradenoma was performed, focusing in particular on the
      presence of Langerhans cells (LCs) in the tumor, and their immunohistochemical
      and ultrastructural characterization. The patient was a woman in her mid-forties
      who underwent resection of two tumors of the head that were 2.0 and 0.7 cm in
      size. They were diagnosed as eccrine spiradenoma and were composed of small and
      large tumor cells with a dense fibrous capsule in the dermis.
      Immunohistochemically, staining by antibodies to cytokeratins (AE1/AE3, CAM5.2)
      and CK 5/6 was diffusely positive in all tumor cells, although not in
      intermingled LCs, which harbored interdigitated nuclei. The cytoplasm of LCs was
      positive for S-100 protein and CD1a, and their nuclei were also occasionally
      positive for S-100 protein. Antibody to epithelial membrane antigen was positive
      for the surface of both intracytoplasmic and true glandular lumina. Fine
      structural examination revealed the presence of LCs among the tumor cells,
      extending fine irregular processes among the tumor cells. Birbeck granules were
      clearly demonstrated in the cytoplasm of LCs. Other fine structural findings
      included intracytoplasmic lumina with microvilli on their surfaces in some tumor
      cells. In these examinations of eccrine spiradenoma, LCs, approximately 15/HPF in
      the tumor, were distinctly detected even at light microscopic level as negative
      for various types of cytokeratin stains, although they were positive for S-100
      protein and CD1a, whereas on ultrastructural examination Birbeck granules were
      demonstrated in their cytoplasm. Determination of the significance of these LCs
      in eccrine spiradenoma requires further investigation of a larger number of
      cases.

PMID- 18085384
TI  - Invasive micropapillary carcinoma of the colon: an immunohistochemical study.
AB  - Invasive micropapillary carcinoma has recently been reported in various anatomic
      sites. In this article, we report a case of micropapillary carcinoma of the
      sigmoid colon. A 70-year-old Japanese woman presented with bloody stool for 2
      months. Detailed examination disclosed ulcerative and localized tumor in the
      sigmoid colon. Histological examination of the colon tumor showed a combination
      of conventional adenocarcinoma (60%) and micropapillary carcinoma (40%).
      Immunohistochemically, micropapillary carcinoma cells were positive for
      cytokeratin (CK) 20, carcinoembryonic antigen, and CA125, but negative for CK7,
      thyroid transcription factor-1, surfactant apoprotein A, estrogen receptor, and
      progesterone receptor. Additionally, the immunohistochemistry of epithelial
      membrane antigen revealed reverse polarity of neoplastic cells. Results of
      conventional adenocarcinoma were basically identical to those of micropapillary
      carcinoma. In the stroma of both conventional adenocarcinoma and micropapillary
      carcinoma, many myofibroblasts were present and CD34-positive stromal cells were
      absent. Finally, we report the fourth case of micropapillary carcinoma arising in
      the colon. Immunohistochemical results of CK7(-)/CK20(+) strongly suggest the
      colon as a primary site of micropapillary carcinoma. Additionally, micropapillary
      carcinoma of the colon may cause a similar stromal reaction to conventional
      adenocarcinoma of the colon.

PMID- 18085385
TI  - CKD-MBD: impact on management of kidney disease.
AB  - Chronic kidney disease (CKD) causes various bone mineral disorders, which have
      recently been named CKD mineral and bone disorder (CKD-MBD). CKD-MBD is
      associated with extremely high cardiovascular disease (CVD) morbidity and
      mortality in the endstage kidney disease (ESKD) population. Thus, optimal
      management of CKD-MBD would lead to a reduction in cardiovascular morbidity and
      mortality in uremic patients. In addition, it has been suggested that the
      treatment of CKD-MBD has some favorable effects on the progression of CKD.
      Recently, novel therapeutic agents, including active vitamin D analogues,
      noncalcium-containing phosphate binders, and cinacalcet, have become clinically
      available. In this article, we review novel therapeutic strategies for CKD-MBD.

PMID- 18085386
TI  - Label-retaining cells in the kidney: origin of regenerating cells after renal
      ischemia.
AB  - The kidney is capable of regeneration. In response to a variety of insults, renal
      epithelial tubular cells dedifferentiate into an immature phenotype, proliferate,
      migrate to the injured area, and redifferentiate into mature polarized epithelial
      cells. In animal models of acute kidney injury induced by renal ischemia or renal
      toxins, various growth factors, transcription factors, chemokines, and
      extracellular matrix components have been demonstrated to be involved in the
      regeneration process. Recent research has suggested the existence of renal
      stem/progenitor cells in the kidney and their involvement in renal regeneration.
      In this review, we will focus on the mechanisms of tubular regeneration after
      kidney injury, particularly on label-retaining cells actively engaged in this
      process, and discuss their potential as targets of regenerative therapy for
      various kidney diseases.

PMID- 18085387
TI  - Saireito probably prevents mesangial cell proliferation in HIGA mice via PDGF-BB
      tyrosine kinase inhibition.
AB  - BACKGROUND: In this study, we administered saireito to high serum IgA (HIGA) mice
      and investigated its inhibitory effect on platelet-derived growth factor (PDGF)
      receptor tyrosine kinase (which causes mesangial proliferation) as one of the
      possible antinephritic mechanisms of saireito. METHODS: Female HIGA/NscSlc mice,
      aged 10 weeks, were divided into five groups (each, n = 12; a control group,
      three saireito-mixed feed groups, and a captopril-mixed feed group) so that the
      plasma IgA levels were comparable among the groups. After the grouping, the
      animals were administered the saireito or captopril, mixed in the feed, until the
      age of 45 weeks. RESULTS: At the age of 45 weeks, the glomerular cell number was
      47.8 +/- 3.9 / cross section in the HIGA mice in the control group, but 41.6 +/-
      2.3 / cross section in the 1.3% saireito-mixed feed group and 38.7 +/- 3.5 /
      cross section in the captopril-mixed feed group, being significantly lower in
      both these treatment groups than in the control group. At the age of 45 weeks,
      the sclerosis score in the HIGA mice in the control group was 0.92 +/- 0.23.
      However, the sclerosis scores in the 0.26% (0.59 +/- 0.26) and 1.3% (0.58 +/-
      0.16) saireito-mixed feed groups were significantly lower than that in the
      control group. In the captopril-mixed feed group, the sclerosis score was 0.64 +/
      0.34, significantly lower than that in the control group. It was clarified that
      saireito suppressed mesangial cell proliferation without showing any
      cytotoxicity. Furthermore, as a result of investigating the mesangial cell
      proliferation-suppressing effect similarly with the 23 substances constituting
      saireito, a proliferation-suppressing effect was recognized with
      isoliquiritigenin (a component of Glycyrrhizae Radix) and oroxylin A (a component
      of Scutellariae Radix). Oroxylin A and isoliquiritigenin showed an inhibitory
      effect on PDGF receptor tyrosine kinase. Furthermore, the inhibitory effects of
      oroxylin A and isoliquiritigenin on tyrosine kinase were found to be specific to
      the PDGF receptor, and showed no influence on the tyrosine kinase activities of
      other growth-factor receptors examined. CONCLUSION: These results suggest that
      the antinephritic effects of saireito in HIGA mice may be partly due to the
      inhibiton of PDGF tyrosine kinase by oroxylin A and isoliquiritigenin, components
      of saireito.

PMID- 18085388
TI  - Clinical and laboratory features of hyponatremia-induced myopathy.
AB  - BACKGROUND: The present study was undertaken to determine the clinical and
      laboratory features of hyponatremia-induced myopathy. METHODS: We collected 14
      hyponatremic subjects (six men and eight women) with serum creatine kinase (CK)
      levels of more than 500 IU/ml during the 5-year period between 2001 and 2005. The
      mean +/- SD patients' age was 66.5 +/- 16.7 years (range, 37 to 88 years).
      RESULTS: The causes of the hyponatremia were: syndrome of inappropriate secretion
      of antidiuretic hormone (SIADH; n = 4), mineralocorticoid-responsive hyponatremia
      of the elderly (MRHE; n = 2), hypopituitarism (n = 1), psychogenic polydipsia (n
      = 3), congestive heart failure (n = 3), and unknown cause (n = 1). The subjects
      were subgrouped into two groups: acute onset of myopathy and slowly progressive
      onset. The age at onset was 62.0 +/- 5.7 years (mean +/- SEM) in the subjects
      with acute onset, and 77.8 +/- 1.5 years in those with slowly progressive onset
      (P = 0.02). At the onset, there was no difference in serum Na levels between the
      acute onset and the slowly progressive onset groups, but there was a significant
      difference in maximal serum CK levels between the groups (7072 +/- 2317 vs 722 +/
      104 IU/ml; P = 0.02). Maximal serum CK levels were widely distributed among the
      ages in the subjects with acute onset, whereas maximal serum CK levels were
      mildly elevated in the elderly subjects with slowly progressive onset. The
      elevated serum CK levels were normalized at a maximum of 14 days after the onset
      in all the subjects. CONCLUSIONS: The present findings indicate that hyponatremia
      infrequently causes skeletal muscle disruption, and that there are two types of
      hyponatremia-induced myopathy, acute onset and slowly progressive onset.

PMID- 18085389
TI  - C4d Immunohistochemistry in glomerulonephritis with different antibodies.
AB  - BACKGROUND: The presence of C4d in the kidney is generally detected particularly
      for the diagnosis of antibody-mediated rejection in renal transplants. In frozen
      sections of immunofluorescence (IF) staining with anti-C4d monoclonal antibodies
      (mAbs), we noted intrinsic C4d deposition even in normal glomeruli though their
      pathogenic or an intrinsic role is unkown. An anti-C4d polyclonal antibody
      (C4dpAb), which is suitable for paraffin immunoperoxidase (IP) staining, is less
      used than mAbs, and it has demonstrated that intrinsic C4d is not evident. To
      establish a stable and reproducible procedure for C4d detection with the C4dpAb
      and to determine the staining characteristics of it, the present study aimed to
      test whether the method was comparable with IF with a mAb. METHODS: We compared
      the C4dpAb with the mAb in adjacent sections of human diseased kidneys, and then
      compared IP with IF of C4dpAb. Two ways of antigen retrieval was examined for IP.
      RESULTS: On comparing the two antibodies for glomerular staining with IF, we
      found that the pattern and intensity (C4dpAb showed intrinsic C4d with IF) were
      similar. In addition, C4dpAb staining with IP and IF demonstrated that the
      intrinsic staining in the normal glomerulus was mostly undetectable by IP,
      whereas IF showed distinct staining. Likewise, C4d deposition with IP in some
      cases was apparently weaker than that on IF, suggesting that this deposition is
      not intrinsic but indicates pathogenic complement activation. CONCLUSIONS: The
      advantage of the C4dpAb for immunohistochemistry is of value for reconsidering
      the role of C4d in glomerular diseases.

PMID- 18085390
TI  - Clinical analysis of 207 patients who developed renal disorders during or after
      treatment with edaravone reported during post-marketing surveillance.
AB  - BACKGROUND: The post-marketing surveillance of edaravone has reported serious
      adverse reactions, including renal and hepatic disorders. Renal disorders were
      the most frequently reported serious/important adverse reactions, which led to
      the evaluation of their causation by edaravone, their severity, and the recovery
      of renal function. METHODS: A retrospective review was carried out of 207
      Japanese patients with acute stroke who developed renal disorders on edaravone
      treatment. RESULTS: No particular factor other than edaravone was found as a
      possible cause of the renal disorders in 17 patients (8.2%). In 91.8% of the
      patients evaluated, factors other than edaravone were associated with the
      development of renal disorders. Severe deterioration of systemic status (e.g., a
      severe infection or a decrease in blood pressure) was considered to be a highly
      probable cause of renal disorders that occurred before or during treatment with
      edaravone in 135 patients (65.2%). Fifty-nine patients (28.5%) underwent blood
      purification treatment (BPT). In the remaining 148 patients without BPT, the peak
      serum creatinine (SCr) level during follow-up was 3 mg/dl or more in 93 patients
      (44.9%) and less than 3 mg/dl in 55 patients (26.6%). The severity of renal
      disorders was moderate to severe in 73.3% of the 207 patients, and renal function
      recovered in 43%. CONCLUSIONS: Appropriate treatment of deteriorated systemic
      status and the discontinuation of edaravone administration following the early
      discovery of renal disorders are recommended to reduce the development of severe
      renal disorders during edaravone treatment. The precise role(s) of edaravone in
      the pathogenesis of renal disorders should be evaluated in the future.

PMID- 18085391
TI  - Histologically advanced IgA nephropathy treated successfully with prednisolone
      and cyclophosphamide.
AB  - BACKGROUND: No definitive therapeutic consensus has been established for
      progressive immunoglobulin A nephropathy (IgAN). METHODS: We retrospectively
      investigated 35 patients with histologically advanced IgAN. The patients were
      divided into two groups: 27 received prednisolone and cyclophosphamide (PSL+CPA
      group) and 8 received supportive treatment (control group). The initial doses of
      PSL and CPA were 30 mg/day and 50 mg/day, respectively. PSL was tapered to 2.5
      mg/day over 2 years and CPA was discontinued at 6 months. RESULTS: In the control
      group, mean follow-up duration was 22.9 months, renal progression rate was -20.9
      x 10(-3) dl/mg per month, and all patients developed endstage renal disease
      within 5 years. In the PSL+CPA group, mean follow-up duration was 64.3 months,
      renal progression rate was -1.5 x 10(-3) dl/mg per month, and renal survival at 5
      years was 89.8%. Renal prognosis was markedly improved in the PSL+CPA group
      compared with the control group. The patients in the PSL+CPA group were divided
      into two subgroups according to baseline serum creatinine (<2 mg/dl or > or =2
      mg/dl); renal survival in the two subgroups was similar (84.4% versus 100% at 5
      years). Adverse effects of PSL+CPA were minimal and mild. CONCLUSIONS: It is
      possible that PSL+CPA therapy safely improved the renal prognosis of patients
      with severe IgAN who would otherwise have required dialysis therapy within 5
      years. However, a prospective, multicenter clinical trial is required to prove
      the effects and safety of this treatment.

PMID- 18085392
TI  - Evaluation of serum fetuin-A relationships with biochemical parameters in
      patients on hemodialysis.
AB  - BACKGROUND: Complications associated with atherosclerosis in dialysis patients
      are attracting attention. Fetuin-A, a circulating calcium-regulatory glycoprotein
      that inhibits vascular calcification, is associated with inflammation and outcome
      in dialysis patients. In this study, the relation between serum fetuin-A
      concentration and biochemical parameters in patients on hemodialysis was
      investigated. METHODS: Forty hemodialysis patients, 22 men and 18 women, aged 57
      +/- 12 years; and 20 controls, 10 men and 10 women, aged 50 +/- 10 years,
      participated in this study. We measured serum fetuin-A by enzyme-linked
      immunosorbent assay. The biochemical parameters of serum albumin, alkaline
      phosphatase, calcium, phosphate, intact parathyroid hormone, total cholesterol,
      triglyceride, lipoprotein (a), brain natriuretic peptide (BNP), highly sensitive
      C-reactive protein (hsCRP), hemoglobin, and hematocrit in whole blood were also
      measured before starting dialysis sessions. Other parameters included the cardio
      ankle vascular index, age, mean arterial pressure, total weekly urea clearance
      (Kt/V), smoking habit, body mass index (BMI), and duration of dialysis. These
      variables were included in simple regression analysis. RESULTS: Levels of serum
      fetuin-A in the hemodialysis patients (331 +/- 55 microg/ml) were significantly
      lower than those in the healthy controls (361 +/- 55 microg/ml; P < 0.05). There
      was a negative correlation between serum fetuin-A levels and duration of dialysis
      (r = -0.37, P < 0.01), BNP (r = -0.37, P < 0.001), and hsCRP (r = -0.40, P <
      0.01), and a positive association with serum albumin (r = 0.31, P < 0.05).
      CONCLUSIONS: These data suggest that a low fetuin-A level is a useful predictor
      of malnutrition and inflammation, as well as being a useful predictor of the
      cardiac failure caused by an increased ventricular load in hemodialysis patients.

PMID- 18085393
TI  - Hepatic dysfunction in kidney transplant recipients: prevalence and impact on
      graft and patient survival.
AB  - BACKGROUND: Liver disease has emerged as an important cause of morbidity and
      mortality in renal transplant recipients. Liver insufficiency is the cause of
      death in up to 28% of long-term survivors after renal transplantation. The aim of
      this work was to evaluate the prevalence and causes of hepatic dysfunction in
      renal transplant recipients in Egypt, and its impact on both renal graft function
      and patient survival. METHODS: This study comprised 447 kidney transplant
      recipients who received their grafts between January 1999 and December 2003 at
      Mansoura Urology and Nephrology Center. Among these recipients, 104 patients
      showed persistent hepatic dysfunction, while the remaining 343 had normal liver
      function or transient hepatic dysfunction of less than 6 months' duration.
      RESULTS: We found that the prevalence of persistent hepatic dysfunction in our
      recipients was 23.3%. Infections such as hepatitis C virus (HCV;, with longer
      dialysis duration and blood transfusion as risk factors), HBV, and
      cytomegalovirus (CMV), were the main causes of persistent hepatic dysfunction.
      Drugs (e.g., the sirolimus and tacrolimus; cyclosporine; and azathioprine) were
      also associated with hepatic dysfunction. We did not find a significant impact of
      hepatic dysfunction on either patient or graft survival. CONCLUSIONS: Viral
      infections-especially HCV and CMV-were more prevalent in the group of patients
      with persistent hepatic dysfunction, with duration of dialysis as an important
      risk factor for HCV infection. Dose-dependent cyclosporine-induced hepatic
      dysfunction was observed early post-transplant. Neither tacrolimus- nor sirolimus
      associated hepatic dysfunction was dose-dependent. Hepatic dysfunction had no
      significant impact on either patient or graft survival; however, this finding may
      be due to the relatively short duration of follow up.

PMID- 18085394
TI  - Fatal diffuse pulmonary arterial thrombosis as a complication of nephrotic
      syndrome.
AB  - A 21-year-old man was admitted to our hospital because of leg edema. Because
      laboratory findings revealed massive proteinuria and hypoproteinemia, he was
      diagnosed as having nephritic syndrome caused by minimal change disease. He was
      given a continuous heparin infusion and intravenous steroid therapy, at a
      prednisolone dose of 1 mg/kg per day, and his condition gradually improved. Five
      months after discharge, the patient's proteinuria relapsed. He was readmitted to
      our hospital and we restarted anticoagulant treatment with intravenous heparin
      and 60 mg prednisolone. On the third hospital day, he complained of chest pain
      with sudden onset and dyspnea. He quickly developed shock and died. The findings
      of an autopsy confirmed the presence of diffuse fibrin thrombi in bilateral
      pulmonary arteries, and we diagnosed the cause of death as diffuse pulmonary
      artery thrombosis. A coagulation test for activated partial thromboplastin time
      (aPTT) had already shown that aPTT was prolonged before the initiation of
      treatment. There may have been a deficit of antithrombin III (ATIII) - a cofactor
      of heparin - because of the proteinuria; thus, the continuous heparin treatment
      might not have been effective for the prevention of thrombosis. Alternatives to
      heparin treatment that do not suppress AT III, such as nafamostat mesilate or
      argatroban, which do not require the presence of AT III for their anticoagulant
      action, should be considered in cases similar to the that in the patient reported
      here. In patients with nephrotic syndrome who exhibit altered coagulation test
      results, the choice of anticoagulation therapy for treatment of the
      hypercoagulabilty status associated with nephrotic syndrome should be carefully
      considered.

PMID- 18085395
TI  - Enterococcal endocarditis associated with crescentic glomerulonephritis.
AB  - Glomerulonephritis secondary to infective endocarditis (IE) is an uncommon
      diagnosis and is usually associated with cardiac valvular infection by blood
      culture-positive bacteria. We report a case of necrotizing glomerulonephritis
      associated with culture-positive endocarditis caused by Enterococcus faecalis.
      The patient presented with renal abnormalities and was further investigated by
      renal biopsy. He had immune complex-mediated necrotizing and crescentic
      glomerulonephritis with mesengial and capillary deposition of immunoglobulin M
      (Ig M), Ig G, and complement 3 (C3). He was treated with antibiotics, including
      ampicillin and gentamicin. In addition, steroid and cyclophosphamide were
      administered. The patient died of renal failure 48 days after hospital admission.
      In conclusion, glomerulonephritis caused by Enterococcus faecalis endocarditis is
      an immune-complex-mediated disease characterized by necrotizing and crescentic
      glomerular lesions that can be fatal despite aggressive antimicrobial and
      immunosuppressive therapy.

PMID- 18085396
TI  - MPO-ANCA-positive IgA nephropathy successfully treated with tonsillectomy.
AB  - A 20-year-old Japanese woman was admitted to a hospital because of gross
      hematuria. She was diagnosed with IgA nephropathy with a poor prognosis, based on
      the formation of many crescents in the glomerulus and monocyte infiltration in
      the interstitium in a renal biopsy specimen in February 2003. Myeloperoxidase
      (MPO)-antineutrophil cytoplasmic antibody (ANCA) was not identified at that time.
      After treatment with high-dose steroid pulse therapy and heparin/warfarin, her
      urinary protein improved, to 0.5 g/day. However, 1 year after the steroid pulse
      therapy, urinary protein was increased to 1.2 g/day, associated with repeated
      episodes of tonsillitis. A second renal biopsy was performed, and showed an
      improving tendency, compared to the findings of the previous one, although some
      crescent formation and adhesions of Bowman's capsule remained. Interestingly, MPO
      ANCA was positive in the serological examination done at this time. One month and
      a half after the second renal biopsy, she had a tonsillectomy, followed by a
      regimen of 5 mg oral prednisolone daily, in order to prevent the progression of
      IgA nephropathy. After the tonsillectomy, her urinary protein level was markedly
      improved, at 0.14 g/day. Her creatinine clearance was ameliorated, at 102 ml/min,
      and in addition, MPO-ANCA had disappeared. This case suggests that an
      inflammation such as tonsillitis may be associated not only with the activity of
      IgA nephropathy but also with the production of MPO-ANCA.

PMID- 18085397
TI  - Adult height of three renal transplant patients after growth hormone therapy.
AB  - Three girls with normal growth hormone secretion had received renal
      transplantation when aged 2 to 6 years. They had had severely retarded growth (SD
      for height score was -7.4 to -3.7) at the time of transplantation. After renal
      transplantation, steroid was withdrawn and they were treated with recombinant
      human growth hormone; they subsequently reached adult heights of 145 to 156 cm.
      The SD for adult height score was -2.6 to -0.3. The adult height in two patients
      was over their target height, calculated using the mean of the parents' height.
      This report shows the efficacy of steroid withdrawal and recombinant human growth
      hormone therapy in achieving adult height in these three girls after renal
      transplantation.

PMID- 18085398
TI  - What does the circulating AHSG/fetuin-A level tell us?

PMID- 18085399
TI  - Role of cardiac computed tomography in patients with suspected coronary artery
      disease: interaction with nuclear cardiology.
AB  - Coronary computed tomography (CT) angiography (CTA) and myocardial perfusion
      single photon emission CT (SPECT, or MPS) provide complementary information on
      vascular structure and myocardial perfusion. In patients with coronary artery
      disease (CAD), the combination of both methods is helpful for disease detection
      and therapeutic strategy planning. This article addresses the utility of coronary
      CTA with current 64-row multidetector CT instruments, MPS, and the combination of
      these methods in the evaluation of CAD.

PMID- 18085400
TI  - Srinagarind Hospital experience in concurrent chemoradiation for 100 patients
      with stage IB2 to IVA uterine cervical cancer.
AB  - PURPOSE: The aim of this study was to determine responses, acute adverse effects,
      and survival outcomes of women with stage IB2 to IVA treated with weekly
      cisplatin concurrent with pelvic irradiation at Srinagarind Hospital. MATERIALS
      AND METHODS: The medical records of 100 women with cervical cancer stage IB2 to
      IVA who were treated with weekly cisplatin 40 mg/m(2) concurrent with pelvic
      radiotherapy at Srinagarind Hospital between January 2003 and June 2006 were
      reviewed and analyzed. RESULTS: During the study period, 100 women were eligible
      for analysis, with a mean age of 46 years (range 24-60 years). Distribution
      according to International Federation of Gynecology and Obstetrics (FIGO) staging
      was IB2 1.0%, IIB 47.0%, IIIB 51.0%, and IVA 1.0%, respectively. A total of 86
      patients received five or more cycles of weekly cisplatin. Grade 3 and 4
      hematologic toxicities were found in 6.0%. The overall response rate was 97.0%.
      Complete response was achieved in 86 patients (86.0%) and partial response in 11
      patients (11.0%). Stable disease was found in 1 patient (1.0%) but no progressive
      disease was found. Progression-free survival and overall survival rate were 69.6%
      and 96.1%, respectively. CONCLUSION: Weekly cisplatin (40 mg/m(2)) concurrent
      with pelvic irradiation for locally advanced cervical cancer was effective with
      acceptable toxicity in Thai women.

PMID- 18085401
TI  - Postprocessing technique with MDCT data improves the accuracy of the detection of
      lung nodules.
AB  - PURPOSE: The aim of this study was to determine whether postprocessing techniques
      could improve the accuracy of detecting lung nodules. MATERIALS AND METHODS: A
      total of 154 segmented lung volumes of multidetector-row computed tomography
      (MDCT) data were the subject of the study. Lung nodules were present in 88
      volumes and absent in 66 volumes. We prepared four groups: (1) 7- or 10-mm thick
      section axial images; (2) 1-mm thin-section axial images; (3) sliding slab
      maximum intensity projection (MIP) images with a slab thickness of 15 mm; and (4)
      sliding slab volume rendering (VR) images with a slab thickness of 15 mm. Sixteen
      physicians reviewed each group in interactive cine mode. The observers'
      performance in the detection of lung nodule was evaluated by receiver operating
      characteristic (ROC) analysis. RESULTS: The observers' performance of the MIP and
      VR groups was significantly better than in other two groups. There was no
      significant difference statistically between the thin and thick groups.
      CONCLUSION: The detectability of lung nodules is improved with the use of sliding
      slab MIP and VR using thin-section image data. Thin-section volume data are
      essential for improving diagnostic accuracy, but observation of thin-section
      images without utilization of image-processing techniques dose not improve
      diagnostic accuracy.

PMID- 18085402
TI  - Experimental verification of the utility of positron emitter nuclei generated by
      photonuclear reactions for X-ray beam monitoring in a phantom.
AB  - PURPOSE: The utility of positron emitter nuclei generated by photonuclear
      reactions was verified for X-ray beam monitoring in a phantom. MATERIALS AND
      METHODS: Positron emission tomography-computed tomography (PET-CT) images of a
      gelatinous water phantom (H(2)O target) and a polyethylene phantom (CH(2) target)
      were acquired 5 min after delivering a dose of 17 Gy with an X-ray beam energy of
      21 MV. Reconstructed PET images and the calculated half-life showed that the
      positron emitters of (15)O (half-life 122.2 s) in the H(2)O target and (11)C
      (half-life 20.4 min) in the CH(2) target were generated by photonuclear
      reactions. RESULTS: A comparison was made between measured activity and dose
      distributions for each target. The measured times of annihilation gamma rays from
      the positron emitter nucleus were 10 and 30 min for the (15)O nucleus in the
      H(2)O target and the (11)C nucleus in the CH(2) target, respectively. The
      activity distributions of the (15)O and (11)C positron emitter nuclei were
      similar to the measured dose distributions for both depth and lateral directions
      except for dose buildup and collimator edge regions. It was confirmed that no
      activity was detected at an X-ray energy of 14 MV, which was far below the energy
      threshold for both photonuclear reactions. CONCLUSION: It was estimated that the
      PET-CT image acquired from the activity of the (15)O and (11)C positron emitter
      nuclei might provide the area of X-ray beam irradiation in a phantom.

PMID- 18085403
TI  - Electrocardiography-triggered high-resolution CT for reducing cardiac motion
      artifact: evaluation of the extent of ground-glass attenuation in patients with
      idiopathic pulmonary fibrosis.
AB  - PURPOSE: The aim of this study was to evaluate the decreasing of cardiac motion
      artifact and whether the extent of ground-glass attenuation of idiopathic
      pulmonary fibrosis (IPF) was accurately assessed by electrocardiography (ECG)
      triggered high-resolution computed tomography (HRCT) by 0.5-s/rotation
      multidetector-row CT (MDCT). MATERIALS AND METHODS: ECG-triggered HRCT were
      scanned at the end-diastolic phase by a MDCT scanner with the following scan
      parameters; axial four-slice mode, 0.5 mm collimation, 0.5-s/rotation, 120 kVp,
      200 mA/rotation, high-frequency algorithm, and half reconstruction. In 42
      patients with IPF, both conventional HRCT (ECG gating(-), full reconstruction)
      and ECG-triggered HRCT were performed at the same levels (10-mm intervals) with
      the above scan parameters. The correlation between percent diffusion of carbon
      monoxide of the lung (%DLCO) and the mean extent of ground-glass attenuation on
      both conventional HRCT and ECG-triggered HRCT was evaluated with the Spearman
      rank correlation coefficient test. RESULTS: The correlation between %DLCO and the
      mean extent of ground-glass attenuation on ECG-triggered HRCT (observer A: r = 
      0.790, P < 0.0001; observer B: r = -0.710, P < 0.0001) was superior to that on
      conventional HRCT (observer A: r = -0.395, P < 0.05; observer B: r = -0.577, P =
      0.002) for both observers. CONCLUSION: ECG-triggered HRCT by 0.5 s/rotation MDCT
      can reduce the cardiac motion artifact and is useful for evaluating the extent of
      ground-glass attenuation of IPF.

PMID- 18085404
TI  - Dose attenuation effect of hip prostheses in a 9-MV photon beam: commercial
      treatment planning system versus Monte Carlo calculations.
AB  - PURPOSE: The purpose of this study was to investigate the dosimetric effect of
      various hip prostheses on pelvis lateral fields treated by a 9-MV photon beam
      using Monte Carlo (MC) and effective path-length (EPL) methods. MATERIAL AND
      METHODS: The head of the Neptun 10 pc linac was simulated using the MCNP4C MC
      code. The accuracy of the MC model was evaluated using measured dosimetric
      features including depth dose values and dose profiles in a water phantom. The
      Alfard treatment planning system (TPS) was used for EPL calculations. A virtual
      water phantom with dimensions of 30 x 30 x 30 cm(3) and a cube with dimensions of
      4 x 4 x 4 cm(3) made of various metals centered in 12 cm depth was used for MC
      and EPL calculations. Various materials including titanium, Co-Cr-Mo, and steel
      alloys were used as hip prostheses. RESULTS: Our results showed significant
      attenuation in absorbed dose for points after and inside the prostheses.
      Attenuations of 32%, 54% and 55% were seen for titanium, Co-Cr-Mo, and steel
      alloys, respectively, at a distance of 5 cm from the prosthesis. Considerable
      dose increase (up to 18%) was found at the water-prosthesis interface due to back
      scattered electrons using the MC method. The results of EPL calculations for the
      titanium implant were comparable to the MC calculations. This method, however,
      was not able to predict the interface effect or calculate accurately the absorbed
      dose in the presence of the Co-Cr-Mo and steel prostheses. CONCLUSION: The dose
      perturbation effect of hip prostheses is significant and cannot be predicted
      accurately by the EPL method for Co-Cr-Mo or steel prostheses. The use of MC
      based TPS is recommended for treatments requiring fields passing through hip
      prostheses.

PMID- 18085405
TI  - Definitive radiotherapy for medically inoperable early-stage serous and clear
      cell uterine carcinoma.
AB  - High-risk, early-stage endometrial cancer is optimally treated by hysterectomy
      followed by adjuvant radiotherapy. In 1%-9% of cases, the patient is medically
      unfit or personally unwilling to undergo primary surgery, and definitive
      radiotherapy may be offered as an alternative definitive therapy. Although
      several series have reported excellent intrauterine control and disease-specific
      survival for endometrioid histology, few outcome data are available for patients
      with serous or clear cell histology treated with radiotherapy alone. We herein
      describe one case each of early-stage, medically inoperable serous/clear cell
      histology endometrial cancer treated with definitive radiotherapy. Treatment was
      well tolerated by both patients, and neither patient required a treatment break.
      Acute toxicity consisted of self-limited cystitis in one patient. One patient was
      without evidence of disease progression at 54 months after radiotherapy.

PMID- 18085406
TI  - Inflammatory pseudotumor of the kidney with renal artery penetration.
AB  - Inflammatory pseudotumor (IPT) is a quasineoplastic lesion that most commonly
      involves the lung and the orbit; kidney involvement is rare. We report a case of
      inflammatory pseudotumor of the kidney. The patient was a 61-year-old man who
      presented with no symptoms. Nonenhanced computed tomography (CT) demonstrated an
      ill-defined, isodensity mass measuring 3.5 cm in the lower portion of the left
      kidney. Contrast-enhanced CT showed that branches of the renal artery without
      encasement penetrated the tumor; there was a little enhancement in the mass on
      the arterial phase and homogeneous enhancement on the venous phase. On magnetic
      resonance imaging the mass showed intermediate signal intensity on T1-weighted
      images (T1WIs) and low signal intensity on T2WIs. Most IPTs of the kidney appear
      as an ill-defined, hypovascular, homogeneous tumor on CT images, with variable
      signal intensity on MRI T1WIs and low signal intensity on T2WIs. Our case had the
      same imaging findings, with branches of the renal artery penetrating the tumor.
      If the renal tumor has these radiological findings, the tumor may be IPT.

PMID- 18085407
TI  - Bilateral popliteal artery entrapment syndrome: reemphasis on reading axial
      tomograms.
AB  - A 33-year-old man with bilateral popliteal artery entrapment syndrome (PAES)
      presented with right calf claudication. He underwent radiological studies
      including conventional arteriography, multidetector row CT (MDCT), and magnetic
      resonance imaging (MRI) of the lower extremities. He had been fine since birth
      and athletic in his school days. Axial tomographic images by MDCT and MRI at the
      popliteal fossa bilaterally showed an anomalous medial head of the gastrocnemius
      muscle between the popliteal artery and vein, resulting in right popliteal artery
      occlusion and leading to the diagnosis of bilateral PAES type II. MDCT or MR
      facilitates noninvasive computer-aided arteriography and is often utilized for
      screening patients with claudication for peripheral arterial diseases. However,
      axial tomograms are more essential for confirming PAES than arteriography, and
      radiologists should continue to look for possible abnormalities on popliteal
      fossa tomograms because early diagnosis of PAES allows better choices and
      outcomes of treatment.

PMID- 18085408
TI  - Reversible widespread ischemia after early reperfusion detected by initial
      diffusion-weighted magnetic resonance imaging.
AB  - We herein report the time-related dynamic changes according to the diffusion
      weighted image (DWI) findings after a cerebral ischemic attack in a 63-year-old
      woman. At 2 weeks after undergoing a lower limb amputation due to diabetic
      atherosclerosis, she experienced a sudden loss of consciousness and right
      hemiparesis. Magnetic resonance image revealed left frontal and parietal areas
      with an increased signal on the DWI, and magnetic resonance angiography (MRA)
      showed the left middle cerebral artery to be occluded at the superior M2 branch.
      However, on the next day the lesion on DWI, except for the gray matter, was
      observed to have almost completely resolved, and MRA showed complete
      recanalization of the left superior M2 branch with diminished clinical symptoms.
      Although a few cases of reversible DWI-identified lesions have been described in
      the literature, the occurrence of large, reversed DWI lesions in the middle
      cerebral artery territory with severe apparent diffusion coefficient decreases,
      as seen in our case, are exceedingly rare.

PMID- 18085409
TI  - Proteomic analysis of RNA-binding proteins in dry seeds of rice after
      fractionation by ssDNA affinity column chromatography.
AB  - In proteomic analysis, one of the major limitations is the detection of low
      abundance proteins. To detect low-abundance RNA-binding proteins in mature dry
      seeds of rice, fractionation by single stranded DNA (ssDNA) affinity column
      chromatography was carried out before analysis by two-dimensional gel
      electrophoresis (2-DE). Proteomic analysis of the ssDNA-binding fraction revealed
      the existence of three types of RNA-binding proteins, including a K homology (KH)
      domain containing protein, a putative RNA-binding protein and a glycine-rich RNA
      binding protein, in mature seeds. In addition, decreases in the putative RNA
      binding protein and glycine-rich RNA-binding protein after absorbing water in
      seeds appear to be associated with seed germination.

PMID- 18085410
TI  - Optimisation of NMR dynamic models I. Minimisation algorithms and their
      performance within the model-free and Brownian rotational diffusion spaces.
AB  - The key to obtaining the model-free description of the dynamics of a
      macromolecule is the optimisation of the model-free and Brownian rotational
      diffusion parameters using the collected R (1), R (2) and steady-state NOE
      relaxation data. The problem of optimising the chi-squared value is often assumed
      to be trivial, however, the long chain of dependencies required for its
      calculation complicates the model-free chi-squared space. Convolutions are
      induced by the Lorentzian form of the spectral density functions, the linear
      recombinations of certain spectral density values to obtain the relaxation rates,
      the calculation of the NOE using the ratio of two of these rates, and finally the
      quadratic form of the chi-squared equation itself. Two major topological features
      of the model-free space complicate optimisation. The first is a long, shallow
      valley which commences at infinite correlation times and gradually approaches the
      minimum. The most severe convolution occurs for motions on two timescales in
      which the minimum is often located at the end of a long, deep, curved tunnel or
      multidimensional valley through the space. A large number of optimisation
      algorithms will be investigated and their performance compared to determine which
      techniques are suitable for use in model-free analysis. Local optimisation
      algorithms will be shown to be sufficient for minimisation not only within the
      model-free space but also for the minimisation of the Brownian rotational
      diffusion tensor. In addition the performance of the programs Modelfree and Dasha
      are investigated. A number of model-free optimisation failures were identified:
      the inability to slide along the limits, the singular matrix failure of the
      Levenberg-Marquardt minimisation algorithm, the low precision of both programs,
      and a bug in Modelfree. Significantly, the singular matrix failure of the
      Levenberg-Marquardt algorithm occurs when internal correlation times are
      undefined and is greatly amplified in model-free analysis by both the grid search
      and constraint algorithms. The program relax ( http://www.nmr-relax.com ) is also
      presented as a new software package designed for the analysis of macromolecular
      dynamics through the use of NMR relaxation data and which alleviates all of the
      problems inherent within model-free analysis.

PMID- 18085411
TI  - Optimisation of NMR dynamic models II. A new methodology for the dual
      optimisation of the model-free parameters and the Brownian rotational diffusion
      tensor.
AB  - Finding the dynamics of an entire macromolecule is a complex problem as the model
      free parameter values are intricately linked to the Brownian rotational diffusion
      of the molecule, mathematically through the autocorrelation function of the
      motion and statistically through model selection. The solution to this problem
      was formulated using set theory as an element of the universal set [formula: see
      text]-the union of all model-free spaces (d'Auvergne EJ and Gooley PR (2007) Mol
      BioSyst 3(7), 483-494). The current procedure commonly used to find the universal
      solution is to initially estimate the diffusion tensor parameters, to optimise
      the model-free parameters of numerous models, and then to choose the best model
      via model selection. The global model is then optimised and the procedure
      repeated until convergence. In this paper a new methodology is presented which
      takes a different approach to this diffusion seeded model-free paradigm. Rather
      than starting with the diffusion tensor this iterative protocol begins by
      optimising the model-free parameters in the absence of any global model
      parameters, selecting between all the model-free models, and finally optimising
      the diffusion tensor. The new model-free optimisation protocol will be validated
      using synthetic data from Schurr JM et al. (1994) J Magn Reson B 105(3), 211-224
      and the relaxation data of the bacteriorhodopsin (1-36)BR fragment from Orekhov
      VY (1999) J Biomol NMR 14(4), 345-356. To demonstrate the importance of this new
      procedure the NMR relaxation data of the Olfactory Marker Protein (OMP) of Gitti
      R et al. (2005) Biochem 44(28), 9673-9679 is reanalysed. The result is that the
      dynamics for certain secondary structural elements is very different from those
      originally reported.

PMID- 18085413
TI  - Exposure to 9-cis retinoic acid induces penis and vas deferens development in the
      female rock shell, Thais clavigera.
AB  - To clarify how tributyltin (TBT) and triphenyltin (TPT) interact with the
      retinoid X receptor (RXR) to induce growth of male sex organs in female
      gastropods, we treated female rock shells (Thais clavigera) with three different
      concentrations (0.1, 1, or 5 microg/g wet wt) of 9-cis-retinoic acid (9CRA) or
      with a single concentration (1 microg/g wet wt) of TBT, TPT, or fetal bovine
      serum (as a control). The effects of each treatment were measured as the
      incidence of imposex, the length of the penis-like structure, and the vas
      deferens sequence (VDS) index. 9CRA induced imposex in a dose-dependent manner;
      imposex incidence was significantly higher in the rock shells that received 1 (P
      < 0.05) or 5 microg (P < 0.001) 9CRA than in the controls. After 1 month, the
      rock shells treated with 5 microg 9CRA exhibited substantial growth of the penis
      like structure that was not as evident in the other treated shells. The length of
      the structure differed between the 0.1- and 5-microg 9CRA treatment groups (P <
      0.05) but not between the 1- and 5-microg 9CRA treatment groups (P > 0.05).
      Compared with the control, the VDS index increased significantly in the 1- (P <
      0.05) and 5-microg (P < 0.001) 9CRA groups. The penis-like structures behind the
      right tentacle in female rock shells treated with 5 microg 9CRA were essentially
      the same as the penises and vasa deferentia of normal males and of TBT-treated or
      TPT-treated imposexed females. These results further support the hypothesis that
      imposex in gastropods could be mediated by RXR.

PMID- 18085415
TI  - Predictors of colorectal cancer screening behaviors among average-risk older
      adults in the United States.
AB  - OBJECTIVE: To critically evaluate recent studies that examined determinants of
      CRC screening behaviors among average-risk older adults (>or=50 years) in the
      United States. METHODS: A PUBMED (1996-2006) search was conducted to identify
      recent articles that focused on predictors of CRC initiation and adherence to
      screening guidelines among average-risk older adults in the United States.
      RESULTS: Frequently reported predictors of CRC screening behaviors include older
      age, male gender, marriage, higher education, higher income, White race, non
      Hispanic ethnicity, smoking history, presence of chronic diseases, family history
      of CRC, usual source of care, physician recommendation, utilization of other
      preventive health services, and health insurance coverage. Psychosocial
      predictors of CRC screening adherence are mostly constructs from the Health
      Belief Model, the most prominent of which are perceived barriers to CRC
      screening. CONCLUSIONS: Evidence suggests that CRC screening is a complex
      behavior with multiple influences including personal characteristics, health
      insurance coverage, and physician-patient communication. Health promotion
      activities should target both patients and physicians, while focusing on
      increasing awareness of and accessibility to CRC screening tests among average
      risk older adults in the United States.

PMID- 18085414
TI  - Cancer screening in France: subjects' and physicians' attitudes.
AB  - OBJECTIVE: Since screening for cancer has been advocated, funded, and promoted in
      France, it is important to evaluate the attitudes of subjects in the general
      population and general practitioners (GPs) toward cancer screening strategies.
      METHODS: EDIFICE is a nationwide opinion poll that was carried out by telephone
      among a representative sample of 1,504 subjects living in France and aged between
      40 and 75 years and among a representative sample of 600 GPs. The questionnaire
      administered to subjects queried about previous screening for cancer. RESULTS:
      Ninety-three percent of women stated that they had undergone at least one
      mammography. Although rated "A" recommendation-strongly recommended-by the US
      Preventive Services Task Force, screening for colorectal cancer received less
      attention than prostate cancer screening which is rated "I"-insufficient evidence
      (reported screening rates of 25% and 36%, respectively). Six percent of subjects
      stated that they had undergone lung cancer screening. GPs' attitudes toward
      cancer screening showed similar inconsistencies. CONCLUSIONS: It thus appears
      that understanding of cancer screening practices in the French general population
      does not match scientific evidence. To a lesser extent, this also holds for GPs.

PMID- 18085416
TI  - An innovative approach to inventory and monitoring of natural resources in the
      Mexican State of Jalisco.
AB  - This paper discusses the statistical design and estimation processes developed
      for the assessment of key land resources relevant to questions of their condition
      and change in the State of Jalisco, Mexico. Some initial results of the first
      phase of Jalisco's Natural Resource Inventory and Monitoring Program (IMRENAT)
      conducted in 2006 are presented and discussed. Since this is a relatively new
      approach for an inventory and monitoring program of this magnitude, designed from
      the beginning specifically for integration with orbital satellite data, it is
      anticipated that changes will have to be made over time to improve conceptual and
      operational design aspects. Alternative remote sensing capabilities to further
      improve local information, more sophisticated analysis to satisfy the
      requirements of officials as they become more aware of the capabilities of the
      system, possible improvements in change assessments over time, and opportunities
      to focus on specific interesting changes will be assessed. As this study
      indicates, current and future information technology advancements provide a solid
      prospect for the development and application of integrative sampling strategies
      to support sustainability science and management processes.

PMID- 18085417
TI  - Dynamics of traffic noise in a tropical city Varanasi and its abatement through
      vegetation.
AB  - Noise level monitoring and its reduction with different width and height of
      vegetation belt were studied in the Varanasi city. Noise level monitoring of the
      Varanasi city revealed the fact that area category A (without vegetation) was
      highly polluted as compare to area category B (with vegetation) having less
      fluctuation of traffic load. Four plant species Putranjeva roxburghi, Cestrum
      nocturnum, Hibiscus rosasinensis and Murraya peniculata were tested for noise
      reduction study at different frequencies. Experiment revealed the fact that H.
      rosasinensis reduced noise highest at both low and high frequencies (100-500 Hz,
      22 dB and 2.5-6.3 KHz 26 dB), followed by M. peniculata (100-500 Hz, 18 dB and
      2.5-6.3 KHz 20 dB), P. roxburghi (100-500 Hz 15 dB and 2.5-6.3 KHz 17 dB) and C.
      nocturnum (100-500 Hz 9 dB and 2.5-6.3 KHz 14 dB). Significance of vegetation
      belt in noise reduction was established with multiple regression models.

PMID- 18085418
TI  - Wind tunnel experimental study on the effect of PAM on soil wind erosion control.
AB  - In recent years, high-molecular-weight anionic polyacrylamide (PAM) have been
      widely tested on a variety of soils, primarily in water erosion control. However,
      little information is available regarding the effectiveness of PAM on preventing
      soil loss from wind erosion. The research adopted room wind tunnel experiment,
      two kinds of soils were used which were from the agro-pastoral area of Inner
      Mongolia, the northwest of China, the clay content of soils were 22.0 and 13.7%,
      respectively. For these tests, all the treatments were performed under the
      condition of wind velocity of 14 m s(-1) and a blown angle of 8.75%, according to
      the actual situation of experimented area. The study results indicated that using
      PAM on the soil surface could enhance the capability of avoiding the wind
      erosion, at the same time, the effect of controlling wind soil erosion with 4 g
      m(-2) PAM was better than 2 g m(-2) PAM's. Economically, the 2 g m(-2) PAM used
      in soil surface can control wind erosion effectively in this region. The prophase
      PAM accumulated in soil could not improve the capability of avoiding the wind
      erosion, owing to the degradation of PAM in the soil and the continual tillage
      year after year. The texture of soil is a main factor influencing the capability
      of soil avoiding wind erosion. Soil with higher clay content has the higher
      capability of preventing soil from wind erosion than one with the opposite one
      under the together action of PAM and water.

PMID- 18085419
TI  - Assessment of some trace heavy metals and radioactivity concentration in water of
      Bendimahi River Basin (Van, Turkey).
AB  - The levels of heavy metals were determined in the water of Bendimahi River Basin,
      statistically analysed and compared to natural gross radioactivity concentration.
      Fifteen samples of water were collected from Bendimahi River and Van Lake for two
      seasons in 2005. Water samples were analyzed for eight trace elements and
      concluded together with gross-alpha and gross-beta radioactivity concentrations.
      Atomic absorption spectrometry (AAS) was used to determine the concentrations of
      heavy metals in water samples collected from Bendimahi River basin. Correlation
      analysis was made for radioactivity and heavy metal concentrations and the
      Pearson correlation coefficients between gross-alpha and gross-beta radioactivity
      and heavy metal were determined. The concentrations of all metals were found to
      be higher than WHO, EC, EPA and TSE-266 guidelines for drinking water, except for
      Zn and Cu. Generally, the heavy metal concentrations in water samples obtained in
      May and in August were found to be in sequence of Fe>Zn>Pb>Cr>Cu>Mn>Co>Cd and
      Fe>Zn>Cu>Pb>Cr>Mn>Co>Cd, respectively. The gross-alpha and gross-beta activity
      concentration varies between 0.063 and 0.782, 0.021 and 0.816 Bq l(-1) in samples
      collected in May, and 0.009 and 0.037, 0.081 and 3.116 Bq l(-1) in samples
      collected in August.

PMID- 18085420
TI  - Heavy metal contamination of road-deposited sediments in a medium size city of
      China.
AB  - Road-deposited sediment (RDS) is an important environmental medium that affects
      the characteristics of heavy metals in stormwater runoff. 62 RDS samples were
      collected from four different land use types (commercial, residential, intense
      traffic and riverside park) in the Zhenjiang city of China. The samples were
      analysed for concentrations of five metals (Zn, Pb, Cu, Cr and Ni). The maximum
      mean concentrations of Zn, Pb, Cu, Cr and Ni from different land use types were
      686, 589, 158, 129 and 125 mg/kg, respectively. The intense traffic area
      displayed the highest metal concentrations, whilst Zn, Cr, Ni and Cu did not show
      any discernible variations among the other three areas. Seven particle sizes were
      analysed separately for the heavy metal concentrations. In all studied areas,
      particles <63 microm have the highest metal concentrations: 926-1,188 mg/kg of
      Zn, 270-928 mg/kg of Pb, 150-220 mg/kg of Cu, 99-172 mg/kg of Cr and 96-147 mg/kg
      of Ni. The fine particle fraction (<63 microm) of the samples accounted for about
      25-60% of the total metal loading; in contrast, the coarsest fraction (1,000
      2,000 microm) only contributed 1-5%. The calculated ecological risk index shows
      that considerably high potential risks exist in the intense traffic area
      particularly due to high concentrations of Pb. These findings provide invaluable
      information for the development of appropriate management strategies to decrease
      nonpoint source contamination loading to the water environment in urban areas.

PMID- 18085421
TI  - Erythrocyte migration and gap formation in rabbit blood clots in vitro.
AB  - Thrombolytic agents must be carried by the blood circulation to thrombi to exert
      their functions. Structural gaps exist between blood vessels and thrombi or in
      the area surrounding thrombi. Therefore, information about fundamental gap
      formation at thrombotic areas is critically important for thrombolytic therapy.
      We previously reported that t-PA accelerates the activities of bovine
      erythrocytes and hemoglobin (Hb) towards bovine plasminogen activation. Here, we
      examined gap generation by observing morphological changes during thrombolytic
      processes in rabbit blood clots deformation of erythrocytes from blood clots and
      Hb transfer from erythrocytes to serum in vitro. Rabbit venous blood samples (1
      ml) were stored under sterile conditions in glass tubes at 37 degrees C for 2,
      24, 48 h, 1, and 2 weeks. We examined clot diameter, erythrocyte diameter and
      number as well as Hb volume in the serum, as well as histological changes in the
      clots. The diameter of blood clots did not change until 2 weeks after sampling.
      Erythrocyte diameter decreased within 48 h and at 2 weeks after sampling at the
      clot surface (p < 0.001) and interior (p < 0.001). The number of erythrocytes in
      the serum started to increase starting from 24 h after sampling (p < 0.01). Serum
      Hb volume also gradually increased from 24 h until 2 weeks after sampling (p <
      0.01). The erythrocyte envelope became disrupted and cytoplasm started to flow
      through pores into the serum at 24 h. The results indicated that blood clots are
      reduced due to clot retraction, erythrocyte dissociation and cytoplasm leakage
      without a distinct fibrinolytic reaction. These results indicated that gaps start
      to form between 2 and 24 h after blood clotting.

PMID- 18085422
TI  - Integration site analysis in transgenic mice by thermal asymmetric interlaced
      (TAIL)-PCR: segregating multiple-integrant founder lines and determining
      zygosity.
AB  - When transgenic mice are created by microinjection of DNA into the pronucleus,
      the sites of DNA integration into the mouse genome cannot be predicted. Most
      methods based on polymerase chain reaction (PCR) that have been used for
      determining the integration site of foreign DNA into a genome require specific
      reagents and/or complicated manipulations making routine use tedious. In this
      report we demonstrate the use of a PCR-based method-TAIL-PCR (Thermal Asymmetric
      Interlaced PCR) which relies on a series of PCR amplifications with gene specific
      and degenerate primers to reliably amplify the integration sites. By way of
      example, using this approach, three separate integration sites were found (on
      chromosomes 8, 15 and 17) in one transgenic founder. As the sites on chromosomes
      8 and 15 failed to segregate in any subsequent progeny, whole chromosome paints
      were done to determine if translocations involving chromosomes 8 and 15 occurred
      at the time of transgene integration. Whole chromosome painting could not detect
      translocations, suggesting that the rearrangements likely involve only small
      stretches of chromosomes. Site-specific primers were used to identify the progeny
      carrying only one integration site; these mice were then used as sub-founders for
      subsequent breedings. Integration site specific primers were used to distinguish
      homozygous progeny from heterozygotes. TAIL-PCR thus provides an easy and
      reliable way to (1) identify multiple integration sites in transgenic founders,
      (2) select breeders with one integration site, and (3) determine zygosity in
      subsequent progeny. Use of this strategy may also be considered to map
      integration sites in situations of unexpected phenotype or embryonic lethality
      while creating new transgenic mice.

PMID- 18085423
TI  - Relationship between aortic valve sclerosis and left ventricular hypertrophy in
      chronic haemodialysis patients.
AB  - BACKGROUND: Cardiac valve calcification is a frequent finding in chronic
      haemodialysis patients. Left ventricular hypertrophy (LVH) is a significant
      predictor of cardiovascular mortality in patients with end-stage renal disease.
      We evaluated the influence of aortic valve sclerosis (AVS) on the development of
      LVH in chronic haemodialysis patients. METHODS: A total of 82 consecutive
      patients (52 male, mean age 48 +/- 12 years) undergoing chronic haemodialysis
      treatment for > 1 year were subjected to echocardiography for the screening of
      AVS and the assessment of transaortic flow velocity and the left ventricular mass
      index (LVMI). The absence (group 1, n = 42) and presence of AVS (group 2, n = 40)
      was established. The average values of systolic, diastolic and pulse pressure
      were obtained. Plasma calcium, phosphorus, intact parathyroid hormone, C-reactive
      protein, haemoglobin and lipid levels were also measured. RESULTS: LVH was
      detected in 59 (72%) of the study patients. The LVMI was higher in the AVS group
      (171 +/- 39 vs. 132 +/- 41 g/m2, p < 0.001). Patients with AVS also had higher
      transaortic flow velocities (1.64 +/- 0.36 vs. 1.21 +/- 0.21 m/s, p < 0.01) and
      maximal pressure gradients (10.8 +/- 7.1 vs. 5.9 +/- 3.4 mmHg, p < 0.01). The
      LVMI showed a direct correlation with transaortic flow velocity in the AVS group
      (r = 0.60, p < 0.01). Stepwise linear regression analysis revealed transaortic
      flow velocity (p = 0.02), pulse pressure (p = 0.01) and haemoglobin levels
      (inverse relationship) (p = 0.02) to be independent predictors of the LVMI.
      CONCLUSION: These data suggest that AVS is strongly and independently
      interrelated with LVH in chronic haemodialysis patients. The underlying mechanism
      might be the valve resistance to left ventricular outflow, as shown by increased
      transaortic flow velocities and maximal pressure gradients in AVS patients.

PMID- 18085424
TI  - Percutaneous injection sclerotherapy with tetracycline hydrochloride in simple
      renal cysts.
AB  - OBJECTIVES: Symptomatic simple renal cysts can be treated by combination of
      percutaneous aspiration and sclerotherapy. A number of sclerosing agents
      including glucose, phenol, iophendylate, polidocanol, minocycline and pantopaque
      have been used in the past to prevent reformation of cyst. In this study,
      tetracycline HCL solution is evaluated as a sclerosant for treatment of simple
      renal cysts. METHODS: Our study treated 76 cysts in 70 patients with symptomatic
      renal cysts. Aspiration and sclerotherapy was performed on 56 cysts, and 20 cysts
      aspirated without sclerotherapy as a control group. Treatment was performed under
      local anesthesia and punctured under ultrasound guidances with an 18-gauge
      needle. Tetracycline HCL (20%) was injected into the cystic cavity according to
      cyst diameter. All patients were followed up with an ultrasound examination at 3
      months, 6 months, and then at yearly intervals. The reduction rate was estimated
      by a comparison of the volume of the cyst before and after treatment. A cyst
      reduction of 50% or greater in diamater was considered as a successful treatment.
      RESULTS: The average follow-up period was 9.8 months in the sclerotherapy group
      and 9.9 months in the control group. The success rate was 85.7% in the
      sclerotherapy group. There was a significant difference in the reduction rate of
      tetracycline HCL sclerotherapy group and control group. No major complications
      were encountered.

PMID- 18085425
TI  - Multifocal symptomatic intracerebral metastases as the first manifestation of
      prostatic carcinoma: a report and literature review.
AB  - We report an unusual case of prostatic carcinoma in a middle-aged man with
      symptomatic multifocal intracerebral metastases as its initial manifestation to
      highlight the importance of its accurate diagnosis and implications on its
      management and review relevant literature.

PMID- 18085426
TI  - Mineral and bone disorder after renal transplantation: a review.
AB  - Chronic kidney disease-mineral bone disorder is a common clinical picture
      encountered in patients with end-stage renal disease and is the result of
      additive pathophysiological processes. Renal transplantation remains the
      treatment of choice for these patients, especially as advances in this field have
      allowed for enhanced allograft survival. However, with increasing success of
      renal transplantation has come a greater appreciation of some of its subsequent
      complications, such as posttransplantation bone disease. Recently, persistent
      hyperparathyroidism and osteopenia-osteoporosis have been given specific
      attention. Traditionally, persistent hyperparathyroidism has been treated with
      parathyroidectomy, although the role that calcimimetics may play in the future is
      promising. Newer aspects to medical management of osteopenia-osteoporosis, such
      as the efficacy of bisphosphonate therapy and early steroid withdrawal, are
      becoming apparent and some of the newer drugs for the treatment of osteoporosis
      are yet to be investigated in this subgroup of patients.

PMID- 18085427
TI  - Experimental supratrigonal cystectomy: II--Evaluation of urinary calculi,
      infection, and bladder dysfunction in the pathogenesis of renal failure.
AB  - The objective of this study was to evaluate the role of urolithiasis, infection,
      and bladder dysfunction in the pathogenesis of renal failure in rats subjected to
      supratrigonal cystectomy. One group of Sprague-Dawley rats was submitted to
      supratrigonal cystectomy, a second to cystectomy during which a suspension of
      Proteus mirabilis was injected into the bladder stump, and a third to sham
      surgery (controls). The animals were sacrificed two months after surgery. Blood
      pressure and serum urea and creatinine were measured before surgery and at
      sacrifice when a careful inspection of the urinary tract was performed to
      determine the presence of hydronephrosis and calculi. Microbiological analyses
      were performed on urine aspirated from the bladder and on the kidneys.
      Significant differences were found between values of systolic blood pressure and
      serum urea and creatinine recorded prior to the surgical procedure and those
      recorded at sacrifice in each group except the control group. Renal failure was
      present in all animals subjected to cystectomy. Urinary calculi were documented
      in 5/10 animals subjected to cystectomy only and in all rats inoculated with P.
      mirabilis. Hypertension was documented in 43.75% of animals subjected to
      cystectomy. Pyelonephritis was diagnosed only in animals with urinary calculi, in
      each of which urine culture was also positive. No cases of renal failure,
      hypertension, calculi, and/or pyelonephritis were detected in the sham group. The
      findings of this study indicate that kidney failure in rats subjected to
      supratrigonal cystectomy is related to the severe bladder dysfunction induced by
      the surgical procedure.

PMID- 18085428
TI  - Cost-of-illness study of severe haemophilia A and B in five French haemophilia
      treatment centres.
AB  - OBJECTIVE: The aim of this study was to assess the consumption of anti
      haemophilic drugs by adults and children with severe haemophilia A or B (residual
      activity of FVIII or FIX < or =2%) and to quantify the average direct medical
      costs. METHOD: A retrospective multicentre cost-of-illness study from the
      perspective of French national health insurance system. The costs include only
      the use of clotting factors. MAIN OUTCOME MEASURE: Consumption was expressed in
      UI/kg/year and costs in euros/kg/year. RESULTS: From January 1, 2001 to December
      31, 2002, data from 81 adults and 30 children with severe haemophilia A (n = 92)
      or B (n = 19) and included in the "SNH" were collected and analysed. A
      coagulation factor inhibitor was present in 10 patients (9%). Four of them were
      high responders. Mean age and body weight were respectively 28 +/- 17 years and
      58 +/- 24 kg. Except for one adult patient, all (99%) had outpatient treatment,
      44 patients (40%) were hospitalized and treated by recombinant or/and plasma
      derived FVIII or FIX or/and rFVIIa. Overall median annual consumption of anti
      haemophilic drugs per patient was estimated at 1,333 UI/kg, with a median cost-of
      illness of 1,156 euros/kg. Patients with severe haemophilia B consumed more than
      patients with severe haemophilia A, though not significantly (P = 0.096), with a
      median of 2,167 vs. 1,100 UI/kg/year and a median cost of 1,760 vs. 917
      euros/kg/year (P = 0.13). Children consumed respectively more than adults (P =
      0.008), with a median of 3,204 vs. 1,106 UI/kg/year and a median cost of 2,614
      vs. 913 euros/kg/year (P = 0.012). The median cost for patients with an inhibitor
      was 3,291 euros/kg/year, approximately threefold higher than that of patients
      without an inhibitor (926 euros/kg/year) (P = 0.022). CONCLUSION: It suggests a
      higher consumption and cost of anti-haemophilic drugs among children when
      compared to adults. Haemophilia B patients did not consume significantly more
      than haemophilia A patients, whereas the consumption and cost for patients with
      or without inhibitors differed significantly.

PMID- 18085429
TI  - Association of clinical experiences with patient-reported outcomes among breast
      cancer surgery patients: breast cancer quality care study.
AB  - BACKGROUND: We aimed to clarify the association of breast cancer patients'
      clinical experiences with patient-reported outcomes (PRO) of satisfaction with
      care, choice of the same type of surgery again, and health-related quality of
      life (HRQOL). METHODS: There were 2,403 (25.9%) of 9,283 eligible women who had
      undergone primary curative surgery for breast cancer in one of five selected
      hospitals between 1993 and 2002 who responded to a survey questionnaire including
      information about care experiences, satisfaction with care, and HRQOL. RESULTS:
      Treatment satisfaction was independently associated with cancer recurrence,
      problems obtaining surgery, receiving adjuvant hormonal therapy, being involved
      in treatment decisions, having opinions reflected in treatment decisions,
      experiencing treatment toxicity, or being hospitalized for treatment toxicity (P
      <0.01). Breast-conserving surgery with radiotherapy, receiving adjuvant hormone
      therapy, being involved in treatment decisions, having opinion reflected in
      treatment decisions, having no treatment toxicity, and receiving regular follow
      up care were associated with choosing the same treatment over again (P < 0.01).
      Good care experiences, except for regular follow-ups, were significantly
      associated with good HRQOL in most functioning subscales (P < 0.01). CONCLUSIONS:
      Our findings suggest that timely referral for treatment, reflection of the
      patient's opinions in treatment decisions, and prevention of treatment toxicity
      might be important to HRQOL.

PMID- 18085430
TI  - Low oxygen affinity in reptilian hemoglobin D: prediction of residue interactions
      in Geochelone carbonaria HbD by homology modeling.
AB  - The homology model of hemoglobin D from Geochelone carbonaria, the red-footed
      tortoise was predicted using the 3D structure coordinates of Geochelone gigantea
      hemoglobin D as the template. The model was built using the program, MODELLER
      (8v1) and evaluated with PROCHECK and PROSA. The present study features an in
      depth analysis of the 3D model and its conformational changes brought about with
      variations in its environment. These structural changes are correlated with its
      ability to adapt to different environmental constraints enabling the organism to
      better suit to its natural habitat. The model shows additional contacts between
      amino acid pairs of alpha-119 and beta-55, alpha-35 and beta-124, alpha-103 and
      beta-112, alpha-115 and beta-116, alpha-120 and beta-52, alpha-120 and beta-55,
      alpha-36 and beta-127 which are not found in human hemoglobin. It is predicted
      that these contacts may result in T-state stabilization thus lowering oxygen
      affinity. Furthermore, decrease in the interaction of phosphate heteroatoms with
      the amino acid residues of G. carbonaria Hb was also predicted in this study.

PMID- 18085431
TI  - The Queen's English: an alternative, biosocial hypothesis for the distinctive
      features of "gay speech".
AB  - Popular stereotypes concerning the speech of homosexuals typically attribute
      speech patterns characteristic of the opposite-sex, i.e., broadly feminized
      speech in gay men and broadly masculinized speech in lesbian women. A small body
      of recent empirical research has begun to address the subject more systematically
      and to consider specific mechanistic hypotheses to account for the potentially
      distinctive features of homosexual speech. Results do not yet fully endorse the
      stereotypes but they do not entirely discount them either; nor do they cleanly
      favor any single mechanistic hypothesis. To contribute to this growing body of
      research, we report acoustic analyses of 2,875 vowel sounds from a balanced set
      of 125 speakers representing heterosexual and homosexual individuals of each sex
      from southern Alberta, Canada. Analyses focused on voice pitch and formant
      frequencies which together determine the principle perceptual features of vowels.
      There was no significant difference in mean voice pitch between heterosexual and
      homosexual men or between heterosexual and homosexual women, but there were
      significant differences in the formant frequencies of vowels produced by both
      homosexual groups compared to their heterosexual counterparts. Formant frequency
      differences were specific to only certain vowel sounds and some could be
      attributed to basic differences in body size between heterosexual and homosexual
      speakers. The remaining formant frequency differences were not obviously due to
      differences in vocal tract anatomy between heterosexual and homosexual speakers,
      nor did they reflect global feminization or masculinization of vowel production
      patterns in homosexual men and women, respectively. The vowel-specific
      differences observed could reflect social modeling processes in which only
      certain speech patterns of the opposite-sex, or of same-sex homosexuals, are
      selectively adopted. However, we introduce an alternative biosocial hypothesis,
      specifically that the distinctive, vowel-specific features of homosexual speakers
      relative to heterosexual speakers arise incidentally as a product of broader
      psychobehavioral differences between the two groups that are, in turn, continuous
      with and flow from the physiological processes that affect sexual orientation to
      begin with.

PMID- 18085432
TI  - Initiation, adherence, and retention in a randomized controlled trial of directly
      administered antiretroviral therapy.
AB  - Directly administered antiretroviral therapy (DAART) can improve health outcomes
      among HIV-infected drug users. An understanding of the utilization of DAART
      initiation, adherence, and retention-is critical to successful program design.
      Here, we use the Behavioral Model to assess the enabling, predisposing, and need
      factors impacting adherence in our randomized, controlled trial of DAART versus
      self-administered therapy (SAT) among 141 HIV-infected drug users. Of 88
      participants randomized to DAART, 74 (84%) initiated treatment, and 51 (69%) of
      those who initiated were retained in the program throughout the entire six-month
      period. Mean adherence to directly observed visits was 73%, and the mean overall
      composite adherence score was 77%. These results were seen despite the finding
      that 75% of participants indicated that they would prefer to take their own
      medications. Major causes of DAART discontinuation included hospitalization,
      incarceration, and entry into drug-treatment programs. The presence of depression
      and the lack of willingness to travel greater than four blocks to receive DAART
      predicted time-to-discontinuation.

PMID- 18085433
TI  - Building bridges to evidence-based practice: the MacArthur Foundation Child
      System and Treatment Enhancement Projects (Child STEPs).
AB  - The papers in this special issue describe research undertaken by the MacArthur
      Foundation-funded Research Network on Youth Mental Health. The project is
      designed to understand the challenges of implementing evidence-based treatments
      in community-based mental health practices. This Introduction and the following
      articles describe the impetus and conceptual framework underlying one cluster of
      the Network's activity-i.e., the Clinic Systems Project (CSP). The CSP studies
      examined the organizational and service system environments in a large national
      sample of community mental health and affiliated organizations that provide
      services to children. The main goal is to identify leverage points for, and
      barriers to, the adoption and implementation of evidence-based practices for
      children.

PMID- 18085434
TI  - Assessing the organizational social context (OSC) of mental health services:
      implications for research and practice.
AB  - The organizational social context in which mental health services are provided is
      believed to affect the adoption and implementation of evidence-based practices
      (EBPs) as well as the quality and outcomes of the services. A fully developed
      science of implementation effectiveness requires conceptual models that include
      organizational social context and tools for assessing social context that have
      been tested in a broad cross-section of mental health systems. This paper
      describes the role of organizational social context in services and
      implementation research and evaluates a comprehensive contextual measure, labeled
      Organizational Social Context (OSC), designed to assess the key latent constructs
      of culture, climate and work attitudes. The psychometric properties of the OSC
      measure were assessed in a nationwide study of 1,154 clinicians in 100 mental
      health clinics with a second-order confirmatory factor analysis of clinician
      responses, estimates of scale reliabilities, and indices of within-clinic
      agreement and between-clinic differences among clinicians. Finally, the paper
      illustrates the use of nationwide norms in describing the OSC profiles of
      individual mental health clinics and examines the cross-level association of
      organizational-level culture and climate with clinician-level work attitudes.

PMID- 18085435
TI  - Mexican American adolescents' cultural orientation, externalizing behavior and
      academic engagement: the role of traditional cultural values.
AB  - This study of 598 7th grade students of Mexican origin examined the role of
      traditional cultural values as a mediator of the effects of immigrant status,
      Mexican cultural orientation and Anglo cultural orientation on adolescent
      externalizing behavior and academic engagement. Immigrant status of adolescents
      and their maternal caregivers uniquely predicted increased Mexican cultural
      orientation and decreased Anglo cultural orientation, and both Mexican and Anglo
      cultural orientation related positively to adolescents' endorsement of
      traditional cultural values. Endorsement of traditional cultural values related,
      in turn, to decreased externalizing behaviors and increased academic engagement
      and these findings were replicated across adolescent and teacher report of these
      two outcomes. Tests of mediation provided further evidence to support these
      pathways. Findings support the central importance of traditional cultural values
      as a protective resource that explains why immigrant youth exhibit fewer
      externalizing problems and increased academic engagement when compared to their
      second and third generation peers.

PMID- 18085436
TI  - Significant rate accelerated synthesis of glycosyl azides and glycosyl 1,2,3
      triazole conjugates.
AB  - An efficient and significantly rapid access of a series of glycosyl azides and
      glycosyl 1,2,3-triazole conjugates is reported using modified one-pot reaction
      conditions. In both cases yields were excellent and single diastereomers were
      obtained.

PMID- 18085437
TI  - Recent advances in the toxicology of methylmercury in wildlife.

PMID- 18085438
TI  - Body weight and length of residence in the US among Chinese Americans.
AB  - BACKGROUND: It has been shown that as immigrants' length of residence increases,
      so does their weight. However, little is known about factors associated with
      weight status among Chinese Americans, one of the fastest growing immigrant
      populations in the US. METHODS: Baseline data from a National Cancer Institute
      funded longitudinal study involving a multi-stage probability sample of Chinese
      Americans residing in two communities in New York City were collected. RESULTS:
      Chinese Americans had a low BMI (mean = 22.81) and a lower proportion of obese
      individuals compared with other ethnic groups in the US reported in the
      literature. While the prevalence of being overweight (21%) and obese (2%) was
      low, length of residence was positively associated with weight status (P <
      0.005). CONCLUSIONS: Innovative strategies to help Chinese Americans maintain
      healthy weight status and to prevent them from becoming overweight and obese are
      needed.

PMID- 18085439
TI  - A novel pressure film approach for determining the force imparted by clear
      removable thermoplastic appliances.
AB  - The force imparted by removable thermoplastic appliances (RTA) onto teeth has not
      been investigated in the past. This investigation was designed to explore a novel
      methodology to measure the magnitude and identify the pattern of this force.
      Eight patients with moderate malocclusion were selected. In each patient, the
      palatally mal-positioned upper first premolar was corrected by wearing a series
      of four ClearSmile RTA over a duration of 8 weeks. When constructing RTA, the
      ClearSmile Company was advised that the amount of movement to be programmed into
      each appliance was 0.5 mm. The Pressurex film was used to measure the pressure
      generated by ClearSmile RTA against the palatal surface of the upper first
      premolar for buccal tipping movement. Three measurements were conducted
      respectively upon the issue and retrieval of each appliance (after 2 weeks of
      wear), resulting in 24 pressure measurements for each patient. Digital imaging
      and spectrophotometry analysis were employed to quantify the stain intensity
      mounted by the pressure on the films. The irrelevant forces were subtracted out
      to allow an assessment of the force purely acting to buccally repositioning the
      tooth. The results revealed that (1) the mean force magnitude over 2 weeks of RTA
      wear was 1.12 N (SE = 0.72 N); (2) the higher force magnitude of 5.12 N (SE =
      0.80 N) seen at the issue of the appliance declined drastically to -2.67 N at the
      time of retrieval. These findings suggest that ClearSmile RTA exerts a high level
      of force against the tooth to be moved at the initial stage followed by a rapid
      force diminish.

PMID- 18085440
TI  - Recombinant human erythropoietin attenuates hepatic injury induced by
      ischemia/reperfusion in an isolated mouse liver model.
AB  - INTRODUCTION: Apoptosis is a central mechanism of cell death following
      reperfusion of the ischemic liver. Recombinant human erythropoietin (rhEPO) have
      an important role in the treatment of myocardial ischemia/reperfusion (I/R)
      injury, by preventing apoptosis. The aim of the study was to investigate the
      effect of different regimens of rhEPO in preventing apoptosis following I/R
      induced hepatic injury. MATERIAL AND METHODS: Isolated mouse livers were randomly
      divided into five groups: (1) control group, perfused for the whole study period
      (105 min); (2) 30-min perfusion followed by 90 min of ischemia and 15 min of
      reperfusion; (3), (4) and (5) like group 2, but with administration of rhEPO
      5,000 units/kg i.p. at 30 min, 24 h, or both 30 min and 24 h respectively, before
      induction of ischemia. Perfusate liver enzyme levels and intrahepatic caspase-3
      activity were measured, and apoptotic cells were identified by morphological
      criteria, TUNEL assay, and immunohistochemistry for caspase-3. Using immunoblot
      the expression of the proapoptotic JNK and inhibitor of NFkappaB (IkappaBalpha)
      were also evaluated. von Willebrand factor (vWF) immunohistochemistry was used as
      a marker of endothelial cells. RESULTS: Compared to the I/R livers, all 3 rhEPO
      pretreated groups showed: a significant reduction in liver enzyme levels (P <
      0.05) and intrahepatic caspase-3 activity (P < 0.05), fewer apoptotic hepatocytes
      (P < 0.05) and positive vWF staining in numerous endothelial cells lining the
      sinusoids. EPO decreased JNK phosphorylation and the degradation of the inhibitor
      of NFkappaB (IkappaBalpha) during I/R. There was no added benefit of the multiple
      over the single-dose rhEPO regimen. CONCLUSION: Pretreatment with one dose of
      rhEPO can attenuate post-I/R hepatocyte apoptotic liver damage. NFkappaB and JNK
      activation is likely to play a pivotal role in the pathophysiology of I/R hepatic
      injury and might have a key role in EPO-mediated protective effects. This effect
      is associated with the increase in sinusoidal vWF immunostaining suggests an
      additional effect of rhEPO in liver angiogenesis recovery. These findings have
      important implications for the potential use of rhEPO in I/R injury during liver
      transplantation.

PMID- 18085441
TI  - Power, technology and social studies of health care: an infrastructural
      inversion.
AB  - Power, dominance, and hierarchy are prevalent analytical terms in social studies
      of health care. Power is often seen as residing in medical structures,
      institutions, discourses, or ideologies. While studies of medical power often
      draw on Michel Foucault, this understanding is quite different from his proposal
      to study in detail the "strategies, the networks, the mechanisms, all those
      techniques by which a decision is accepted" [Foucault, M. (1988). In Politics,
      philosophy, culture: Interviews and other writings 1977-84 (pp. 96-109). New
      York: Routledge]. This suggestion turns power into a topic worth investigating in
      its own right rather than a basic analytical resource. It also suggests that
      technologies form an integral part of the networks and mechanisms, which produce
      and redistribute power in medical practice. The paper first engages critically
      with a number of recent discussions of technology and power in health care
      analysis. It then formulates an alternative conception of this relationship by
      drawing on Foucault and historian of science and technology Geoffrey C. Bowker's
      notions of infrastructural inversion and information mythology. Illustration is
      provided through a case study of a wireless nursing call system in a Canadian
      hospital.

PMID- 18085443
TI  - Memory prediction accuracy in younger and older adults: a cross-sectional and
      longitudinal analysis.
AB  - Across three experiments, the effects of age and normative information on memory
      prediction accuracy were examined. In Experiment 1, younger and older adults were
      given an arbitrary midpoint anchor and made global predictions about how they
      expected to perform on subsequent verbal, visual, and name-face memory tasks. In
      Experiment 2, the normative information was varied by providing participants with
      a midpoint anchor, accurate anchor, or no anchor. Across both experiments, older
      adults successfully adjusted their predictions in accordance with the task
      demands, regardless of the type of normative information given. In Experiment 3,
      older adults' prediction accuracy was measured at a 5-year follow-up. Memory
      performance predictions were found to be just as accurate as they had been at the
      first assessment. In general, the findings indicate that older adults were as
      accurate as younger adults in assessing their memory performance abilities. Older
      adults also did not operate on a negative stereotype of global cognitive decline
      with age, as they provided varying performance estimates across the different
      domains and types of memory tasks.

PMID- 18085442
TI  - The predictive significance of autoantibodies in organ-specific autoimmune
      diseases.
AB  - Many organ-specific autoimmune diseases are preceded by a long pre-clinical
      phase, and several longitudinal cohort studies have shown that patients may carry
      autoantibodies many years before they manifest clinical symptoms. Detecting these
      antibodies in serum has been shown to have strong predictive value, depending on
      the particular autoantibody, test method, and disease at issue. This review
      examines the predictive value of various autoantibodies that are found in organ
      specific autoimmune diseases, such as primary biliary cirrhosis, Addison's
      disease, Hashimoto's thyroiditis, type-1 diabetes, celiac disease, and Crohn's
      disease.

PMID- 18085445
TI  - Radiodensity in the central cavity of humeri in high-producing non-commercial
      laying hens.
AB  - 1. Line differences in the incidence of the presence of radiodense material in
      the central cavities of humeri of 6 different lines of laying hens were observed
      using radiographs. 2. Internal humeral radiodense material was observed in over
      60% of hens in two lines and 18% of hens in two other lines measured at 65 weeks
      of age. There was no difference in the incidence (15, 16%) between the last two
      lines observed at 47 weeks of age. 3. In the 4 lines studied at 65 weeks of age
      the presence of radiodense material was associated with increased humerus dry
      weight and ash weight in two lines, while percentage-ash was reduced in all 4
      lines. 4. Results from this and previous studies suggest that humeral medullary
      bone could be an appreciable source of variability in experimental data collected
      to assess skeletal health.

PMID- 18085446
TI  - Growth and lay modelling in a population of Castellana Negra native Spanish hens.
AB  - 1. This study shows the results of (a) fitting growth data to a Gompertz-Laird
      model and (b) fitting egg production per housed bird to a Grossman model, in a
      population of Castellana Negra hens. 2. The maximum growth point for males and
      females, respectively, occurred at 10.6 and 9.3 weeks and the estimated weights
      at maturity were 2852 and 1878 g. Growth curve parameters were lower than those
      of commercial lines and similar to reports of other unselected breeds. 3. The
      start of lay was at 23 weeks. Total egg production reached 163 at 52 weeks, with
      a persistency (length of constant production) of 3.4 weeks and a production
      maximum of 69%. The maximum rate of change segment of the laying curve started at
      24.3 weeks of age, and the production maximum started at 5.8 weeks into lay. The
      rate of decline was 1.4% weekly. 4. The Castellana Negra breed belongs to the
      class of slow-growing light lines and egg production was 163 eggs per calendar
      year.

PMID- 18085447
TI  - Effect of hydrolysed and regular dairy proteins on the texture, colour and
      microstructure of poultry meat emulsions.
AB  - 1. The effects of 2% whole milk proteins, milk protein's two major components
      (caseinate and whey) and some of their fractions (beta-lactoglobulin and two
      hydrolysed whey proteins) were evaluated in a frankfurter-type product made from
      mechanically deboned chicken meat. 2. Adding caseinate, regular whey protein and
      the two whey protein hydrolysates (WPH-I and II) significantly reduced cooking
      loss compared to the control; lowest reduction was obtained with the two
      hydrolysates. 3. Caseinate and regular whey increased hardness, but WPH-I and II
      substantially reduced hardness, fracturability and springiness. 4. The more
      hydrolysed whey (8.5% vs 5.2%; WPH-II vs WPH-I, respectively) caused a greater
      disruption to texture, which could be explained by the light micrographs showing
      an interference with meat protein binding. 5. The most cost-effective ingredient
      tested here was the caseinate.

PMID- 18085448
TI  - Evaluation of pearl millet and flaxseed effects on egg production and n-3 fatty
      acid content.
AB  - 1. A 6-week trial was conducted to evaluate the effects of pearl millet (PM) as a
      replacement for maize, in combination with flaxseed (FS), on productivity, egg
      trait parameters and egg n-3 fatty acid (FA) content in White Leghorn hens. 2.
      Six diet treatments were used: a control (CTL, maize-soybean meal based) diet,
      and diets containing 0, 2, 4, 8 or 12% FS, in which all maize was replaced by PM
      (PM-0, PM-2, PM-4, PM-8 and PM-12, respectively). All diets were isocaloric and
      isonitrogenous and met NRC (1994) requirements. Eight cage replicates per
      treatment were used (three hens per cage). At the end of each week, three eggs
      were randomly collected from each cage to measure egg trait parameters and yolks
      were separated, pooled and lyophilised for FA determination. Body weights and
      feed consumption were recorded weekly. Egg production (number of eggs and egg
      mass produced) was recorded daily. At the end of the experiment, all hens were
      killed to determine liver haemorrhage score. 3. Egg traits and flock performance
      parameters were not different among treatments except at week 4, when birds on
      the PM-12 diet produced smaller eggs than hens on the PM-0 and PM-2 diets. Yolk
      pigmentation scores were lower for the PM-0 and PM-2 diets (1.60 +/- 0.24 and
      1.80 +/- 0.20, respectively), increased with higher inclusions of FS (2.75 +/-
      0.47 for PM-12 diet) but did not reach control levels (6.00 +/- 0.01). Liver
      haemorrhage scores were not affected by dietary treatment. Hens given the PM-8
      and PM-12 diets produced eggs with n-3 FA content higher than required to be
      considered as n-3 FA enriched eggs, and had a lower n-6/n-3 FA acid ratio than
      eggs of hens consuming CTL or the PM based diets with lower FS supplementation.
      4. These results suggest that PM can be used to substitute for maize in the diets
      of layers and may reduce the amount of FS needed to obtain n-3 FA enriched eggs.

PMID- 18085449
TI  - Effects of vitamin E, age and sex on performance of Japanese quail. 1.
      Haematological indices and liver function.
AB  - 1. A trial was conducted to examine the effects of dietary vitamin E content, age
      and sex on haematological indices and liver enzymes of Japanese quails. A total
      of 800 1-d-old quail chicks were assigned at random into 4 equal groups and fed
      on starter and layer diets containing 0, 1, 5 or 10 times the NRC recommended
      supplements of vitamin E. No selenium was added to the basal deficient diets; the
      other diets were supplied with 0.2 mg selenium/kg diet. 2. The investigation
      covered the age span of 3 to 12 weeks in female and male birds. Blood samples
      were collected at 3-week intervals and tested for haematological indices
      (erythrocyte count; leucocyte count; susceptibility of erythrocytes to
      haemolysis; haemoglobin concentration (Hb); packed cell volume (PCV); and mean
      corpuscular volume (MCV)) and liver enzymes (aspartate transaminase, AST, and
      glutathione peroxidase, GSH-Px). 3. The significant differences between the 4
      dietary treatments indicated that as the levels of selenium and/or vitamin E
      increased, the percentage of erythrocytes haemolysed and AST activity decreased,
      whereas Hb and GSH-Px concentrations increased. 4. Differences between age groups
      showed that older quails had higher erythrocyte susceptibility to haemolysis,
      higher AST levels and but lower erythrocyte count and PCV. 5. Females had lower
      erythrocyte haemolysis and higher Hb concentrations than males. 6. The
      interaction between dietary groups and age groups revealed that the differences
      between age groups were reduced as the level of selenium and/or vitamin E
      increased, leading to similar group means over the age period of study. 7. In
      conclusion, NRC recommended supplements of vitamin E (12 and 25 mg/kg diet) were
      not adequate. Doses equal to, at least, 5 times that recommended were advised to
      improve GSH-Px (index of antioxidant status) and Hb concentrations.

PMID- 18085450
TI  - Characterisation of European varieties of triticale with special emphasis on the
      ability of plant phytase to improve phytate phosphorus availability to chickens.
AB  - 1. A total of 30 varieties and selection lines of triticale grown under similar
      conditions were characterised. Thousand grain weight, specific weight, Hagberg
      falling number and N were 50.2 +/- 5.0 g, 72.4 +/- 2.1 kg/hl, 96 +/- 48 s and
      16.1 +/- 0.11 g/kg, respectively. 2. Mean phosphorus (P) concentration was 2.86
      +/- 0.31 g/kg, of which 77% was of phytic origin. Mean phytase activity was 1018
      +/- 319 phytase units (PU)/kg. A genotypic effect on phytase activity was
      detected amongst 5 varieties studied out of 30. Potential and real applied
      viscosities were positively correlated and mean values were 3.53 +/- 0.66 and
      2.15 +/- 0.31 ml/g, respectively. 3. The efficacy of plant phytase in improving P
      availability was assessed in chickens up to 3 weeks of age. Growth performance
      and bone ash concentration were compared in birds given either a maize (450 g/kg)
      and soybean meal (230 g/kg) phosphorus deficient diet containing 3.5 g P/kg, this
      basal diet supplemented with 1 or 2 g P/kg as monocalcium phosphate (MCP) or
      triticale (450 g/kg) and soybean meal (230 g/kg) diets containing 3.2 to 3.8 g
      P/kg with no MCP. To achieve graded levels of phytase activity, 4 varieties of
      triticale, intact or in which phytase was denaturated by heat treatment, were
      used. Estimated metabolisable energy, protein, amino acids and calcium
      concentrations were similar in all diets. 4. Phytase activity in the triticale
      based diets ranged between 135 and 1390 PU/kg. Growth performance and bone ash
      were responsive to plant phytase and to MCP. Non-linear models of these responses
      were adjusted with the best fit for bone ash parameters. The values of 250, 500
      and 1000 PU of plant phytase were estimated to be equivalent to 0.46, 0.67 and
      0.81 g P as MCP, respectively.

PMID- 18085451
TI  - Effects of organic zinc and phytase supplementation in a maize-soybean meal diet
      on the performance and tissue zinc content of broiler chicks.
AB  - 1. The purpose of this study was to investigate the effects of Bioplex Zn (a
      chelated zinc proteinate) and phytase supplementation in a maize-soybean meal
      diet on the performance and tissue zinc (Zn) content of broiler chicks. Treatment
      structure consisted of a 2 x 6 factorial arrangement with two inclusions of
      phytase (0 or 500 PU/kg) and 6 of Bioplex Zn providing 0, 2, 4, 8, 16 and 32 mg
      Zn/kg diet. A total of 864 chicks were randomly assigned to each of 12 dietary
      treatments with 6 replicate cages of 12 chicks. 2. Dietary inclusion of phytase
      increased feed intake, weight gain, plasma Zn content, tibia Zn content, tibia
      and ash weight. 3. Dietary supplementation of Bioplex Zn linearly increased feed
      intake, weight gain, gain to feed ratio, plasma Zn concentration, liver Zn
      concentration, tibia Zn content, tibia and ash weight. 4. An interactive effect
      of phytase and Bioplex Zn on feed intake, weight gain, tibia Zn concentration and
      tibia ash weight was found. 5. One slope, straight broken-line analysis of weight
      gain regressed on the supplemental Zn level provided as Bioplex Zn indicated that
      12 mg/kg supplemental Zn without phytase and 7.4 mg/kg supplemental Zn with
      phytase were required for the optimal weight gain of chicks.

PMID- 18085452
TI  - Effects of concanavalin A on intestinal brush border enzyme activity in broiler
      chickens.
AB  - 1. The effects of Concanavalin A (Con A) on enzymes from the intestinal brush
      border were studied using membrane vesicles (BBMV) prepared from 3- and 6-week
      old broiler chickens. 2. Maltase, sucrase, phytase, alkaline phosphatase and
      leucine aminopeptidase activities were assayed in BBMV in the absence (T0) or
      presence (T1) of Con A, or in the presence of casein (T2). Disaccharidase
      specific activities were assayed in the presence of Con A that had been pre
      incubated with the enzyme (T3) or with the substrate (T4). 3. Con A significantly
      affected maltase and sucrase activities in 3-week-old broiler chicken intestinal
      BBMV. Pre-incubation of the lectin with the maltase or its substrate had no
      effect on enzyme activity. Pre-incubation of Con A with sucrose reduced enzyme
      activity. 4. Con A did not affect phytase, alkaline phosphatase or leucine
      aminopeptidase activities. 5. Maltase, alkaline phosphatase and leucine
      aminopeptidase activities were lower in 6-week-old than in 3-week-old broilers.

PMID- 18085453
TI  - Effects of extrusion conditions on trypsin inhibitor activity of full fat
      soybeans and subsequent effects on their nutritional value for young broilers.
AB  - 1. Increasing proportions of soybeans in poultry diets have highlighted the
      importance of correct processing to inactivate the anti-nutritional factors
      present whilst maintaining protein quality. 2. Ground full fat soybeans (FFSB)
      were extruded using a Clextral laboratory model twin-screw extruder with 0.75 l/h
      of water and end barrel temperatures of 90, 110, 130 and 160 degrees C resulting
      in trypsin inhibitor activities (TIA) of 14.8, 9.6, 4.5 and 1.9 mg/g sample. 3.
      The 4 extrudates were used at three different inclusion levels: 200, 400 and 600
      g/kg semi-synthetic diet and fed to male Ross broiler chicks from d 19 to d 26.
      Digesta samples were taken for measurement of coefficient of ileal apparent amino
      acid digestibility (CIAD) and both pancreas and whole bird weights were measured.
      4. Concentration of ileal apparent digestible lysine was increased from 10.53 to
      17.63 g/kg FFSB by increasing extrusion temperature from 90 to 160 degrees C.
      CIAD of lysine was also improved from 0.58 to 0.86. Other amino acids showed
      similar improvements in both their ileal apparent digestible concentration and
      CIAD. 5. Mean weight gain over 3 d increased linearly from 42 to 95 g per bird
      with increasing extrusion temperatures of FFSB. Pancreatic enlargement was
      evident after 6 d of feeding with FFSB processed at lower temperatures, even when
      the TIA level was at the recommended threshold of 4 mg/g. 6. The results
      emphasise the importance of controlled conditions during processing of FFSB for
      poultry diets and suggest that processing of FFSB in order to reduce TIA levels
      below 4 mg/g may provide significant benefits for broiler chicks.

PMID- 18085454
TI  - Studies on production performance and toxin residues in tissues and eggs of layer
      chickens fed on diets with various concentrations of aflatoxin AFB1.
AB  - 1. An experiment on 1-week-old, White Leghorn female chicks was conducted to
      study the effect of aflatoxin AFB1 on weight gain, feed intake, feed gain ratio,
      age at sexual maturity, production and quality of eggs, retention of nutrients,
      pathoanatomical and histopathological parameters, and also on AFB1 residues in
      eggs and muscles of hens. The chicks were assigned to 4 dietary treatments: D1
      (without AFB1), D2 (2.50 mg/kg AFB1), D3 (3.13 mg/kg AFB1), D4 (3.91 mg/kg AFB1)
      up to the age of 40 weeks. 2. At the end of the experiment, the mean body weight
      gain and feed intake were significantly lower in all aflatoxin-fed groups
      compared to control. The feed gain ratios were noted as 13.41, 13.59, 13.82 and
      14.71, with the group fed the highest concentration of AFB1 showing a
      significantly poorer ratio than other groups. 3. Age at sexual maturity was also
      affected adversely by dietary AFB1: 193 d for D4 as compared to as early as 148 d
      for D1. Hen-d egg production was recorded as 96.92, 74.67, 65.98 and 50.75 in D1,
      D2, D3 and D4, respectively. 4. Average egg weights at the end of the experiment
      were 57.77, 57.49, 57.54 and 54.66 for D1, D2, D3 and D4, respectively. Shape
      index was significantly lower in D4 as compared to control. Contrary to this,
      albumen index was significantly higher in D4 as compared to D1. The values of
      yolk indices and eggshell thickness did not differ significantly among treatment
      groups. However, colour of yolk was reduced in all aflatoxin-fed groups compared
      to control. 5. Retentions of dry matter, crude protein, ether extract, calcium
      and metabolisable energy were adversely affected at various levels of AFB1
      compared to control. 6. Pathoanatomical and histopathological studies showed
      various adverse changes in liver, kidney, heart, ovaries and bursa of Fabricius
      in AFB1-fed groups. 7. Different amounts of aflatoxin residues were detected in
      eggs and breast muscles of hen in all AFB1-fed groups.

PMID- 18085455
TI  - Effect of diet with thiram on liver antioxidant capacity and tibial
      dyschondroplasia in broilers.
AB  - 1. An experiment was conducted to study the effect of thiram on liver antioxidant
      capacity and incidence of tibial dyschondroplasia in broilers. 2. One hundred and
      twenty Avian commercial broilers were allotted at random to three treatments:
      control group, low thiram group (50 mg/kg) and high thiram group (100 mg/kg). 3.
      Blood samples were collected to determine the activity of AST (aspartate
      aminotransferase). At the end of the trial, broilers were killed and liver
      samples were collected to determine the activity of SOD (superoxide dismutase),
      GSH-Px (glutathione peroxidase) and MDA (malondialdehyde) content, while the
      right proximal tibiotarsi were dissected in longitudinal section for assessment
      of tibial dyschondroplasia (TD) incidence and TD score. 4. The results showed
      that thiram increased the incidence of TD and TD scores, increased serum AST
      activity and MDA content of liver, and decreased the activity of SOD and GSH-Px
      in the liver. 5. They suggest that thiram causes TD in broilers by reducing liver
      antioxidation capability and damaging liver function; this may be one of the
      mechanisms by which thiram causes TD in broilers.

PMID- 18085456
TI  - Pre- and post-natal hepatic glucose phosphorylation in chicks (Gallus
      domesticus).
AB  - 1. Hepatic glycogen levels and activities of metabolic enzymes were measured 7 d
      and 2 d before hatching, immediately after hatching and 4 d thereafter. 2.
      Chicken liver has a particle-bound hexokinase with a high K(m) (8 mM) for
      glucose. 3. The results indicate that the high-K(m) hexokinase is involved in the
      mitochondrial generation of ATP for glycogen and lipid synthesis.

PMID- 18085457
TI  - Growth-promoting effects of single-dose intragastrically administered probiotics
      in chickens.
AB  - 1. Live body weight gain (WG) and food conversion efficiency (FCE) were measured
      over a 4-week period in chicks (female, Kabir strain), inoculated
      intragastrically at one week of age with either a single dose (1 ml) of 10(7)
      live bacterial cells of Lactobacillus fermentum (LBF) or a strain of
      Lactobacillus spp. (LB), named Autruche 4 (A4), suspended in 1 ml of phosphate
      buffered saline (PBS, pH 7.0); controls (n = 10) were inoculated only with PBS.
      The same commercial chicken feed was used throughout the 4-week experiment. 2.
      Compared with the control group, WG to 8 and 21 d, and also liver weight, were
      significantly greater in LBF and A4 treatments and FCE improved in both of the
      experimental groups. Compared with the A4 treatment group, WG was significantly
      higher and FCE improved in the LBF-treated group. The effects of A4 treatment on
      chicks were similar to those in an earlier pilot experiment using the same
      methodology but with 1-week-old female chicks (Kabir) inoculated with either the
      A4 strain or strain of LB named Autruche 5. 3. It is concluded that a single dose
      of Lactobacillus fermentum or Lactobacillus spp. (Autruche 4) administered
      intragastrically improves WG and FCE of broiler chicks.

PMID- 18085461
TI  - Effects of water on enzyme performance with an emphasis on the reactions in
      supercritical fluids.
AB  - Enzymes require a certain level of water in their structures in order to maintain
      their natural conformation, allowing them to deliver their full functionality.
      Furthermore, as a modifier of the solvent, up to a certain level, water can
      modify the solvent properties such as polarity/polarizability as well as the
      solubility of the reactants and the products. In addition, depending on the type
      of the reaction, water can be a substrate (e.g., in hydrolysis) or a product
      (e.g., in esterolysis) of the enzymatic reaction, influencing the enzyme turnover
      in different ways. It is found that regardless of the type of reaction, the
      functionality of enzyme itself is maximum at an optimum level of water, beyond
      which the enzyme performance is declined due to the loss in enzyme stability.
      Furthermore, mass transfer limitations caused by pathway blockage and/or by
      reduced solubilities of the reactants and/or products can also affect the enzyme
      performance at higher water levels. Controlling water content of ingoing CO2 and
      substrates as well as precise management of enzyme support and salt hydrates are
      important strategies to adjust water level in reaction media, especially in
      supercritical environments.

PMID- 18085462
TI  - Microbial mannanases: an overview of production and applications.
AB  - Microbial mannanases have become biotechnologically important since they target
      the hydrolysis of complex polysaccharides of plant tissues into simple molecules
      like manno-oligosaccharides and mannoses. The role of mannanases in the paper and
      pulp industry is well established and recently they have found application in the
      food and feed technology, coffee extraction, oil drilling and detergent industry.
      Mannanses are enzymes produced mainly from microorganisms but mannanases produced
      from plants and animals have also been reported. Bacterial mannanases are mostly
      extracellular and can act in a wide range of pH and temperature, though acidic
      and neutral mannanases are more common. This review will focus on complex mannan
      structure and the microbial enzyme complex involved in its complete breakdown,
      mannanase sources, production conditions and their applications in the commercial
      sector. The reference to plant and animal mannanases has been made to complete
      the overview. However, the major emphasis of the review is on the microbial
      mannanases.

PMID- 18085463
TI  - Guayule and Russian dandelion as alternative sources of natural rubber.
AB  - Natural rubber, obtained almost exclusively from the Para rubber tree (Hevea
      brasiliensis), is a unique biopolymer of strategic importance that, in many of
      its most significant applications, cannot be replaced by synthetic rubber
      alternatives. Several pressing motives lead to the search for alternative sources
      of natural rubber. These include increased evidence of allergenic reactions to
      Hevea rubber, the danger that the fungal pathogen Microcyclus ulei, causative
      agent of South American Leaf Blight (SALB), might spread to Southeast Asia, which
      would severely disrupt rubber production, potential shortages of supply due to
      increasing demand and changes in land use, and a general trend towards the
      replacement of petroleum-derived chemicals with renewables. Two plant species
      have received considerable attention as potential alternative sources of natural
      rubber: the Mexican shrub Guayule (Parthenium argentatum Gray) and the Russian
      dandelion (Taraxacum koksaghyz). This review will summarize the current
      production methods and applications of natural rubber (dry rubber and latex), the
      threats to the production of natural rubber from the rubber tree, and describe
      the current knowledge of the production of natural rubber from guayule and
      Russian dandelion.

PMID- 18085464
TI  - Immune mechanisms of corneal allograft rejection.
AB  - Penetrating keratoplasty has been successfully performed on humans for over 100
      years and remains the most common form of solid tissue transplantation. Although
      corneal allografts enjoy a remarkable degree of immune privilege, immune
      rejection remains the leading cause of keratoplasty failure. The immunologic
      basis for corneal allograft rejection was established in animal studies over 50
      years ago, yet large gaps remain in our knowledge regarding the cellular and
      molecular mechanisms of corneal allograft rejection. The enormous redundancy in
      the mammalian immune system creates a condition that favors the development of
      multiple independent immune mechanisms that can produce corneal allograft
      rejection. Although there are few absolute principles, it is certain that the
      immune rejection of corneal allografts is (1) T cell-dependent, (1) heavily
      dependent upon CD4(+) T cells, (3) not restricted to either Th1 or Th2 T cell
      populations, and (4) dependent upon an intact repertoire of resident antigen
      presenting cells.

PMID- 18085465
TI  - Efficacy of once-daily olopatadine 0.2% ophthalmic solution compared to twice
      daily olopatadine 0.1% ophthalmic solution for the treatment of ocular itching
      induced by conjunctival allergen challenge.
AB  - Olopatadine 0.1% (Patanol) and olopatadine 0.2% (Pataday) ophthalmic solutions
      are topical ocular anti-allergic agents with antihistaminic and mast cell
      stabilizing properties. The efficacy of two doses of olopatadine 0.1% was
      compared to one dose of olopatadine 0.2% in the prevention of ocular itching
      associated with allergic conjunctivitis over 24 hours. This double-masked
      conjunctival allergen challenge (CAC) study found no significant difference in
      the mean itching scores between two drops of olopatadine 0.1% and one drop of
      olopatadine 0.2%. Both showed significant activity at the 24-hour time point and
      were statistically superior to placebo. No adverse events occurred while on drug
      therapy.

PMID- 18085466
TI  - A mathematical model of tear mixing under the lower lid.
AB  - PURPOSE: The degree of tear mixing in various parts of eyes plays an important
      role in determining some important aspects of tear dynamics. This study develops
      a mathematical model of tear mixing in the lower conjunctival sac. METHOD: Tear
      mixing in the lower conjunctival sac is modeled using Taylor dispersion. The
      concentration of instilled solutes is obtained numerically from an equation set
      that integrates the mass balance of solutes in the lower conjunctival sac and the
      exposed tear film. RESULTS: The time for dye to appear in the exposed tear film
      and the time for maximal dye concentration after instillation into the lower
      conjunctival sac vary for different amplitudes and frequencies of lid motion. The
      time scales for mixing are in qualitative agreement with experiments reported in
      the literature. CONCLUSION: This study supports the hypothesis that the tear
      mixing in the lower conjunctival sac is driven by Taylor dispersion caused by
      lid/globe movements during blinking.

PMID- 18085467
TI  - The clinical impact and incidence of periocular pigmentation associated with
      either latanoprost or bimatoprost therapy.
AB  - PURPOSE: To evaluate the incidence and characteristics of periocular pigmentation
      with latanoprost versus bimatoprost. METHODS: A retrospective, active-controlled
      comparison of consecutive patients treated with latanoprost or bimatoprost for 12
      months evaluating patients to determine the incidence, characteristics, and
      reversibility of periocular pigmentation. RESULTS: Periocular pigmentation was
      found in 1% patients treated with latanoprost and 6% patients treated with
      bimatoprost within 12 months of beginning treatment (p = 0.004). CONCLUSIONS:
      This study suggests that periocular pigmentation may develop after treatment with
      latanoprost or bimatoprost.

PMID- 18085468
TI  - Polysaccharide-based tissue adhesives for sealing corneal incisions.
AB  - PURPOSE: To investigate the ability of a novel polysaccharide-based tissue
      adhesive to seal corneal incisions, and to determine the effect of the tissue
      adhesive on corneal endothelial cells. METHODS: A polysaccharide-based tissue
      adhesive composed of dextran aldehyde and star PEG amines was applied to a 5-mm
      corneal incision on an enucleated rabbit eye, and the leak pressure of the eye
      was measured. The tissue adhesive was additionally incubated in direct contact
      with bovine corneal endothelial cells to evaluate cytotoxicity. RESULTS: The
      polysaccharide-based tissue adhesive was successful in sealing corneal incisions
      to pressures of > 10 psi (500 mmHg). The tissue adhesive was non-cytotoxic to
      bovine corneal endothelial cells. CONCLUSIONS: Polysaccharide-based tissue
      adhesives are efficacious in sealing corneal wounds and are non-cytotoxic to
      corneal endothelial cells. Such adhesives represent a promising new technology
      for ophthalmic surgery.

PMID- 18085469
TI  - Differential binding of mutant (R116C) and wildtype alphaA crystallin to actin.
AB  - PURPOSE: Quantitate the interaction of mutant (R116C) and wildtype human alphaA
      crystallins with actin. METHODS: AlphaA crystallins, expressed in a recombinant
      system, were purified, followed by passage through an actin affinity column.
      RESULTS: Binding of mutant alphaA crystallin was significantly less than binding
      of wildtype alphaA crystallin. CONCLUSIONS: The R116C mutation of alphaA
      crystallin found in human cataracts binds less to the cytoskeletal component
      actin. Since both alphaA crystallin and actin are necessary for proper
      development of the lens, decreased binding of the mutant protein to actin may
      perturb normal differentiation processes of lens cells which are necessary for
      transparency.

PMID- 18085470
TI  - Citicoline reduces upregulated clusterin following kainic acid injection in the
      rat retina.
AB  - PURPOSE: To investigate the effects of citicoline on upregulated clusterin and
      retinal damage induced by kainic acid (KA). METHODS: KA was injected into the
      vitreous of rats. Effects of systemic citicoline treatments were estimated by
      measuring the thickness of the various retinal layers, immunoblotting, and
      immunohistochemical techniques. RESULTS: One day after KA injection, the
      immunoreactivity of clusterin increased significantly. In rats treated with KA
      plus citicoline, clusterin immunoreactivity was markedly reduced compared to KA
      treated rats. Western blot analysis showed that clusterin protein levels were
      increased in KA-treated rats, but decreased in KA plus citicoline-treated rats.
      Apoptotic cell death was determined by TUNEL method. Citicoline reduced the
      expression of clusterin, as well as the expression of TUNEL after KA injection in
      the rat retina. CONCLUSION: The increased expression of clusterin following KA
      injection in the rat retina suggests the presence of neurodegenerative events;
      citicoline may provide neuroprotection against neuronal cell damage.

PMID- 18085471
TI  - Stromal-derived factor-1 and inflammatory cytokines in retinal vein occlusion.
AB  - PURPOSE: To identify the roles of stromal-derived factor (SDF-1) and inflammatory
      cytokines in retinal vein occlusion (RVO). METHODS: Samples were collected by
      vitrectomy and the levels of SDF-1, vascular endothelial growth factor, and
      inflammatory cytokines (interleukins [IL-1beta, IL-6, IL-8, IL-10, IL-12p70];
      tumor necrosis factor-alpha) were measured in 20 eyes with RVO, and 9 eyes with
      epiretinal membrane served as negative controls. Four eyes with inflammatory
      diseases were also investigated. RESULTS: SDF-1 levels in active RVO (A-RVO; 4
      eyes with iris neovascularization) were significantly higher than those in
      quiescent RVO (Q-RVO; 16 eyes without iris neovascularization) and the negative
      controls (p < .01), whereas there were no significant difference between the Q
      RVO and the negative controls. There were no significant correlations between the
      concentrations of SDF-1 and other cytokines. CONCLUSIONS: Elevation of
      intravitreous SDF-1 levels in A-RVO but not Q-RVO suggested a pivotal role of SDF
      1 in angiogenic changes during RVO.

PMID- 18085472
TI  - Preservation of retinoid influx into eye tissues of ABCR-deficient mice.
AB  - Using an in vivo radiolabeling technique, we investigated the movement of
      retinoid into the retinal pigment epithelium (RPE) of the abcr-/- mouse, which
      lacks the photoreceptor ABCR protein and is a model for Stargardt disease. Eye
      tissues and serum obtained from dark-adapted, 5- to 8-month-old abcr-/- and
      control mice following the intraperitoneal injection of all-trans ((3)H)retinol
      were analyzed to determine the inferred influx of retinoid from the serum into
      the RPE. At 4.5 hr post-injection, the inferred all-trans retinol influx in abcr
      /- mice, which possess the leucine 450 variant of RPE65 protein, was 0.011 +/-
      0.004 nmol (n = 3). This value did not differ significantly from that determined
      in age-matched controls possessing the methionine 450 variant of RPE65 (0.015 +/-
      0.003 nmol; n = 3) or from 3-month-old wildtype mice that possess the leucine 450
      RPE65 variant (0.020 +/- 0.007; n = 4). Thus, the absence of ABCR does not
      significantly compromise the passage of retinoid from the serum into the RPE
      under dark-adapted conditions.

PMID- 18085473
TI  - Induced fit and wit: celebrating the life of Daniel E. Koshland, Jr. (1920 -
      2007).

PMID- 18085474
TI  - Tipping the scales--specifier proteins in glucosinolate hydrolysis.
AB  - Glucosinolates are a group of secondary plant metabolites found in the
      Brassicales order that are beneficial components of our diet, determine the
      flavor of a number of vegetables and spices and have been implicated in pest
      management strategies. These properties, most of the biological activities and
      the pungent odor and taste associated with glucosinolate-containing plants are
      due to the products formed from glucosinolates by their hydrolytic enzymes,
      myrosinases, upon tissue disruption. Specifier proteins impact the outcome of
      glucosinolate hydrolysis without having hydrolytic activity on glucosinolates
      themselves. In the presence of specifier proteins, glucosinolate hydrolysis
      results in nitriles, epithionitriles and organic thiocyanates whose biological
      functions are currently unknown. In contrast, isothiocyanates formed in the
      absence of specifier proteins have been demonstrated to possess a variety of
      biological activities and are thought to protect plants from herbivore and
      pathogen attack. This review discusses the current knowledge on plant and insect
      specifier proteins with special emphasis on their biochemical properties and
      possible mechanisms of action.

PMID- 18085475
TI  - Role of the MRP1/ABCC1 multidrug transporter protein in cancer.
AB  - Multidrug resistance is a major obstacle to cancer treatment and leads to poor
      prognosis for the patient. Multidrug resistance-associated protein 1 (MRP1)
      transports a wide range of therapeutic agents as well as diverse physiological
      substrates and may play a role in the development of drug resistance in several
      cancers including those of the lung, breast and prostate, as well as childhood
      neuroblastoma. The majority of patients with neuroblastoma present with widely
      disseminated disease at diagnosis and despite intensive treatment, the prognosis
      for such patients is dismal. There is increasing evidence that MRP1 is a MYCN
      target gene involved in the development of multidrug resistance in neuroblastoma.
      Given the importance of MRP1 overexpression in neuroblastoma, MRP1 inhibition may
      be a clinically relevant approach to improving patient outcome in this disease.

PMID- 18085476
TI  - Analysis of 5-methylcytosine in DNA of breast and colon cancer tissues.
AB  - 5-methylcytosine (m(5)C) can be used as a sensitive marker of progress of the
      tumor formation induced by the oxidative damage reactions. We have analyzed the
      amount of m(5)C in DNA of patients with breast and colon cancers. Two dimensional
      thin layer chromatography (TLC) has been used to monitor 5-methylcytosine level
      in DNA extracted from cancer tissues. The level of methylation of cytosine at C-5
      position in DNA from breast cancer patients correlates well with the malignancy
      of tumors. Interestingly higher amount of m(5)C in DNA for the breast cancer
      patients treated with different chemotherapeutics was observed. It suggests an
      activation of DNA methyltransferase as well as a genomic suppression of the DNA
      repair genes expression. These differences clearly reflect the health condition
      of patients and support the global analysis of m(5)C in DNA as a good marker for
      diagnosis of neoplasia in clinical practice.

PMID- 18085477
TI  - Modulation of proteasome activity by vitamin E in THP-1 monocytes.
AB  - In THP-1 monocytes, cellular proteasome inhibition by ritonavir or ALLN is
      associated with increased production of oxidative stress. Both compounds produced
      comparable amounts of oxidative stress; however, normalization by alpha
      tocopherol occurred solely after inhibition by ritonavir, and not by ALLN.
      Similar to that, alpha-tocopherol could normalize the reduced formation of 3
      nitrotyrosine-modified proteins only after ritonavir treatment. In the absence of
      any proteasome inhibitor, intrinsic cellular proteasome activity was not
      modulated by alpha-, beta-, and gamma-tocopherols; however, delta-tocopherol,
      alpha-tocotrienol, and alpha-tocopheryl phosphate could significantly inhibit
      cellular proteasome activity and increased the level of p27(Kip1) and p53. Since
      oxidative stress was reduced by alpha-tocopherol only after proteasome inhibition
      by ritonavir and not by ALLN, it is concluded that, in this experimental system,
      alpha-tocopherol does not act as an antioxidant but interferes with the
      inhibitory effect of ritonavir.

PMID- 18085479
TI  - How I became a biochemist.

PMID- 18085478
TI  - Son of Notch, a winged-helix gene involved in boundary formation in the
      Drosophila wing.
AB  - A P element enhancer trap screen was conducted to identify genes involved in
      dorsal-ventral boundary formation in Drosophila. The son of Notch (son) gene was
      identified by the son(2205) enhancer trap insertion, which is a partial loss-of
      function mutation. Based on son(2205) mutant phenotypes and genetic interactions
      with Notch and wingless mutations, we conclude that son participates in wing
      development, and functions in the Notch signaling pathway at the dorsal-ventral
      boundary in the wing. Notch signaling pathway components activate son enhancer
      trap expression in wing cells. son enhancer trap expression is regulated
      positively by wingless, and negatively by cut in boundary cells. Ectopic Son
      protein induces wingless and cut expression in wing discs. We hypothesize that
      there is positive feedback regulation of son by wingless, and negative regulation
      by cut at the dorsal-ventral boundary during wing development.

PMID- 18085480
TI  - Total airborne mold particle sampling: evaluation of sample collection,
      preparation and counting procedures, and collection devices.
AB  - This study was conducted to evaluate (i) procedures used to collect, prepare, and
      count total airborne mold spore/particle concentrations, and (ii) the relative
      field performance of three commercially available total airborne mold
      spore/particle sampling devices. Differences between factory and laboratory
      airflow calibration values of axial fan-driven sampling instruments (used in the
      study) indicated a need for laboratory calibration using a mass flow meter to
      ensure that sample results were accurately calculated. An aniline blue-amended
      Calberla's solution adjusted to a pH of 4.2-4.4 provided good sample
      mounting/counting results using Dow Corning high vacuum grease, Dow Corning 280A
      adhesive, and Dow Corning 316 silicone release spray for samples collected using
      mini-Burkard and Allergenco samplers. Count variability among analysts was most
      pronounced in 5% counts of relatively low mold particle deposition density
      samples and trended downward with increased count percentage and particle
      deposition density. No significant differences were observed among means of 5,
      10, and 20% counts and among analysts; a significant interaction effect was
      observed between analysts' counts and particle deposition densities.
      Significantly higher mini-Burkard and Air-O-Cell total mold spore/particle counts
      for 600x vs. 400x (1.9 and 2.3 x higher, respectively), 1000x vs. 600x (1.9 and
      2.2 x higher, respectively) and 1000x vs. 400x (3.6 and 4.6 x higher,
      respectively) comparisons indicated that 1000x magnification counts best
      quantified total airborne mold spore/particles using light microscopy, and that
      lower magnification counts may result in unacceptable underreporting of airborne
      mold spore/particle concentrations. Modest but significantly higher (1.2x) total
      mold spore concentrations were observed with Allergenco vs. mini-Burkard samples
      collected in co-located, concurrently operated sampler studies; moderate but
      significantly higher mini-Burkard count values (1.4x) were observed in similar
      studies with Air-O-Cell samplers. These count differences were relatively small
      compared with the large differences observed among three count magnifications.

PMID- 18085481
TI  - Longitudinal evaluation of allergen and culturable fungal concentrations in inner
      city households.
AB  - To characterize seasonal variation of three allergens (dust mite, cat, and
      cockroach) and total culturable fungi and to explore whether residential
      characteristics were associated with the concentrations of these agents, floor
      dust was collected from 47 inner-city homes in Minneapolis, Minnesota, over a 1
      year period. A longitudinal analysis of allergen and fungal concentrations was
      carried out using mixed-effect models. Overall, relative humidity was a better
      predictor of allergen concentrations over time than indoor temperature. Seasonal
      variation of cat and cockroach allergens was negligible compared with the
      variability associated with residential characteristics such as race/ethnicity,
      family income, and the presence of cats. Fungal concentrations showed significant
      seasonal variation that outweighed the variability associated with residential
      characteristics. Less than 30% of the dust mite allergen and cockroach allergens
      concentrations were above limits of detection. Observed cockroach allergen
      concentrations were higher in Spanish- and Somali-speaking households than in
      English-speaking households, while English-speaking households had significantly
      higher cat allergen concentrations compared with the other language groups. The
      ratios of within-home to between-home variance for total culturable fungi, dust
      mite, cockroach, and cat allergen concentrations were 2.54, 1.91, 0.55, and 0.24,
      respectively. This ratio is used to predict the number of repeated measurements
      of each allergen required to robustly estimate long-term exposure estimates such
      that exposure misclassification bias is kept within acceptable limits. It is not
      clear whether repeated measurements of dust mite and cockroach allergens are
      required for long-term average exposure because of the large fraction of
      nondetects. It is concluded that a single measurement of cat allergen is a
      reasonable surrogate for long-term average exposure, since repeated measurements
      over time were highly correlated. Total culturable fungi will require greater
      than nine repeated measurements for robust assessment of long-term exposures
      because of low correlations in fungal measures over time.

PMID- 18085483
TI  - Patient blogs: windows into the soul of uveitis care?

PMID- 18085484
TI  - What can physicians learn from the blogs of patients with uveitis?
AB  - AIM: To identify the sources of anxiety from patient blogs. MATERIALS AND
      METHODS: Blogs were identified using www.blogsearch.google.com. and the following
      noted: age, sex, location, type of uveitis, symptoms, and the sources of anxiety.
      RESULTS: 103 blogs were identified. Anterior uveitis was the most common type
      followed by multifocal choroiditis and sympathetic ophthalmia. Sources of anxiety
      include acute pain, redness, photophobia and visual loss, initial misdiagnosis
      and monetary expenses. CONCLUSIONS: Physicians should focus on pain relief and
      counsel on visual loss including its impact on career or livelihood needs.
      Patients seen in emergency situations need early referral.

PMID- 18085485
TI  - Long-term preservation of vision in progressive outer retinal necrosis treated
      with combination antiviral drugs and highly active antiretroviral therapy.
AB  - PURPOSE: To report the successful long-term treatment of varicella zoster virus
      associated progressive outer retinal necrosis (VZV-PORN) with aggressive
      antiviral combination drugs along with highly active antiretroviral therapy
      (HAART). DESIGN: Interventional case report. METHODS: Combined treatment of
      progressive outer retinal necrosis in a university-based tertiary eye hospital
      with ganciclovir implant, intravenous acyclovir (10 mg/kg every 8 h),
      intravitreal foscarnet (2.4 mg), and HAART. RESULTS: Successful treatment of
      progressive outer retinal necrosis with disease remission and preservation of
      20/20 visual acuity out to 1 year. CONCLUSIONS: Combination antiviral therapy and
      HAART may improve long-term visual outcomes for VZV-PORN.

PMID- 18085486
TI  - An epidemic of chronic pseudophakic endophthalmitis due to Ochrobactrum anthropi:
      clinical findings and managements of nine consecutive cases.
AB  - PURPOSE: To report an epidemic of O. anthropi pseudophakic endophthalmitis.
      METHODS: The medical records of nine patients with culture-proven O. anthropi
      endophthalmitis were reviewed. RESULTS: The presenting features were compatible
      to chronic endophthalmitis. Two patients showed coinfections with P. acnes.
      Antibiotics sensitivity test revealed susceptibility to quinolones. Pars plana
      vitrectomy (PPV) with partial capsulectomy (PC) cured infections in seven
      patients without coinfection of P. acnes. Final visual acuity was 20/40 or better
      in five patients. CONCLUSIONS: O. anthropi should be considered in cases with
      chronic pseudophakic endophthalmitis. PPV with PC should be the initial
      therapeutic option for O. anthropi endophthalmitis.

PMID- 18085487
TI  - A prospective evaluation of factors associated with chorioretinitis in patients
      with West Nile virus infection.
AB  - PURPOSE: To identify factors associated with the development and severity of
      chorioretinitis (CR) in patients with West Nile virus (WNV) infection. METHODS:
      Prospective study of 38 patients with WNV infection. RESULTS: Simple analysis
      showed that diabetes (p = 0.027) and age older than 45 years (p = 0.03) were
      significantly associated with CR. When controlling for age, only association
      between diabetes and CR remains statistically significant. Diabetic patients'
      eyes were more likely to have macular involvement (p < 0.0001), 20 or more
      chorioretinal lesions (p < 0.001), and lesion size 500 microm or more (p < 0.01).
      CONCLUSIONS: Diabetes was a risk factor for the development and severity of WNV
      associated CR.

PMID- 18085489
TI  - Acute multifocal placoid pigment epitheliopathy associated with cavernous sinus
      thrombosis.
AB  - Acute multifocal placoid pigment epitheliopathy (AMPPE) has been associated with
      disease of the central nervous system. In this case report, we discuss a patient
      presenting with AMPPE in the setting of a new central nervous system association:
      cavernous sinus thrombosis.

PMID- 18085488
TI  - Stenotrophomonas maltophilia and Mycobacterium chelonae coinfection of the
      extraocular scleral buckle explant.
AB  - PURPOSE: To report a very unusual form of coinfection of the extraocular scleral
      buckle explant by Stenotrophomonas maltophilia and Mycobacterium chelonae.
      DESIGN: Interventional case report. METHODS AND RESULTS: A 61-year-old man had
      infected buckle after uneventful retinal reattachment surgery. Culture showed
      coinfection by Stenotrophomonas maltophilia and Mycobacterium chelonae. This
      concomitance is not random but rather fortified virulence of these otherwise
      facultative pathogens. Organisms responded to broad-spectrum antibiotics.
      CONCLUSIONS: The co-inhabitation of these two low-virulence organisms seems to
      represent an interesting symbiosis with boosting virulence and resistance to host
      defense, especially in those immunocompromised.

PMID- 18085490
TI  - Ocular hypertension associated with ocular sarcoidosis.
AB  - PURPOSE: To report bilateral ocular hypertension in association with ocular
      sarcoidosis. METHODS: Case note review of patients with a diagnosis of
      sarcoidosis-related uveitis. RESULTS: The authors identified 5 patients who
      fulfilled the diagnostic criteria for ocular sarcoidosis and who had intraocular
      pressures of > 40 mmHg in each eye. CONCLUSIONS: Physicians should be aware of
      the association of raised intraocular pressure with ocular sarcoidosis.

PMID- 18085491
TI  - Fibrinous anterior uveitis due to cysticercus cellulosae.
AB  - PURPOSE: To report a case of fibrinous anterior uveitis due to cysticercus
      cellulosae in anterior chamber. DESIGN: Retrospective, interventional case study.
      METHODS: Patient underwent complete ophthalmic and systemic evaluation with
      relevant investigations. Viscoexpression of anterior chamber cysts were done
      under general anaesthesia. RESULTS: A 10-year-old male child presented as
      unilateral fibrinous iridocylitis with secondary glaucoma. Two cysts of
      cysticercus cellulosae were seen after control of inflammation. Complete
      resolution of uveitis occurred once the cysts were removed by viscoexpression.
      CONCLUSION: Cysticercus cellulosae can present as fibrinous anterior uveitis with
      secondary glaucoma. Removal of the cyst can cause complete resolution of uveitis.

PMID- 18085494
TI  - Long-term interleukin-1alpha treatment inhibits insulin signaling via IL-6
      production and SOCS3 expression in 3T3-L1 adipocytes.
AB  - Proinflammatory cytokines are well-known to inhibit insulin signaling to result
      in insulin resistance. IL-1alpha is also one of the proinflammatory cytokines,
      but the mechanism of how IL-1alpha induces insulin resistance remains unclear. We
      have now examined the effects of IL-1alpha on insulin signaling in 3T3-L1
      adipocytes. Prolonged IL-1alpha treatment for 12 to 24 hours partially decreased
      the protein levels as well as the insulin-stimulated tyrosine phosphorylation of
      IRS-1 and Akt phosphorylation. mRNA for SOCS3, an endogenous inhibitor of insulin
      signaling, was dramatically augmented 4 hours after IL-1alpha treatment.
      Concomitantly, the level of IL-6 in the medium and STAT3 phosphorylation were
      increased by the prolonged IL-1alpha treatment. Addition of anti-IL-6
      neutralizing antibody to the medium or overexpression of dominant-negative STAT3
      decreased the IL-1alpha-stimulated STAT3 activation and SOCS3 induction, and
      ameliorated insulin signaling. These results suggest that the IL-1alpha-mediated
      deterioration of insulin signaling is largely due to the IL-6 production and
      SOCS3 induction in 3T3-L1 adipocytes.

PMID- 18085496
TI  - Rhinosurgery in children: basic concepts.
AB  - In newborns, the main supporting structure of the nose is the dorsoseptal
      cartilage, a T-bar-formed complex of septum and upper lateral cartilages, which
      is essentially an external extension of the cartilage of the anterior cranial
      base. Later the anatomic situation gradually changes -- a potential pitfall for
      surgeons and radiologists. The vulnerability of various processes underlying
      postnatal development of the facial skeleton is discussed. The cartilaginous
      septum is the dominant growth center. Loss of septal cartilage at different ages
      leads to different facial syndromes involving nose, maxilla, and orbita. The
      septal cartilage in children demonstrates thinner fracture-prone areas next to
      thicker growth zones. Septum fractures have a preference for the thinner regions,
      corresponding with the most frequent septum deviations observed in growing
      children. The essential problem in pediatric rhinosurgery is not the age-specific
      anatomy but the poor wound-healing capacity: fractured or transected septum
      cartilage will not heal, and disconnected ends tend to overlap, resulting in
      increasing or recurrent deviations. Based on clinical and experimental evidence,
      indications and "safe" and "unsafe" techniques of rhinosurgery are presented for
      children of various age groups.

PMID- 18085497
TI  - Morphological and histological findings after typical surgical manipulations on
      growing septal cartilage in rabbits.
AB  - One remaining problem of nose surgery is surgical correction of a prepubertal
      distortion of the septum. Unfortunately, the growing cartilage reacts differently
      upon a surgical intervention; in most cases this might cause iatrogenic
      disturbance of the development. Our clinical and histological studies with
      polydioxanone (PDS) foil in septal reconstruction showed that the PDS foil
      successfully prevented postoperative sequelae like dislocation of the reimplanted
      cartilage fragments and recurrent deviation caused by overlapping of the
      cartilage borders. Furthermore, it seemed to stimulate cartilage regeneration.
      The question occurs whether the same effect can be expected if growing septal
      cartilage is supported by the PDS foil. This animal study showed remarkable
      effects of the resorbable PDS foil in healing and regeneration of the growing
      septum up to complete resorption of the PDS, which coincidentally paralleled the
      outgrowth of the septal cartilage in rabbits, such as in cartilage regeneration
      and in prevention of secondary septal deviations due to bending of the newly
      formed cartilage or incomplete healing of cut edges.

PMID- 18085498
TI  - Treatment of septal hematomas and abscesses in children.
AB  - The cartilaginous part of the nasal septum of a child with a septal hematoma or
      abscess is at risk of destruction. Consequently, the noses of these children can
      collapse, causing a saddle nose deformity, and in time, the normal outgrowth of
      both the nose and maxilla will be disturbed. In adulthood, they will have an
      underdeveloped saddle nose deformity with too much upward rotation of the nasal
      tip and a retroposition of the midface. Sequelae like these should be prevented
      by prompt diagnosis and surgical intervention. In this article, the management of
      septal hematomas and abscesses is discussed with special focus on reconstruction
      of destructed septal cartilage with the use of autologous cartilage grafts fixed
      to a polydioxanon plate.

PMID- 18085499
TI  - Pediatric rhinoplasty in an academic setting.
AB  - Nasal septal surgery and rhinoplasty are controversial in children.
      Traditionally, an attitude of restraint has been employed by most surgeons till
      an empirical age of 16 to 18 years. This is to avoid the possible adverse effects
      that the growth spurts may have on the nose and midface region. Some authors,
      however, have claimed a paucity of evidence that such untoward effects of surgery
      are frequent. Research has shown that surgical intervention limited to certain
      areas of the bony and cartilaginous nasal framework is less likely to affect
      natural growth patterns. There is a growing consensus toward early intervention,
      especially in a select group of patients, where deferring the surgery may turn
      out to be the poorer option in the short and the long term, and suggestions have
      been made that conservative guidelines may be employed to minimize the
      unwarranted results. This article presents our experience with septorhinoplasty
      in children over the last two decades in an academic setting. We have
      retrospectively studied the pediatric patients who underwent septorhinoplasty at
      the Academic Medical Centre, Amsterdam, Netherlands. There were 106 children aged
      between 3 and 19 years who underwent nasal surgery between February 1994 and
      August of 2007. Sixty-six of these were boys and 40 were girls. Their follow-up
      ranged from 12 to 157 months with a mean follow-up period of 53 months. Eighteen
      patients underwent revision surgery. The clinical circumstances, indications for
      surgery, extent of surgical interference, and outcome in 106 patients are
      discussed. Importantly, the patients in this series have been followed for
      variable periods after puberty and adolescence, allowing for assessment beyond
      the nasal and midfacial growth spurts. Based on our experience, we have outlined
      the clinical guidelines that we follow for surgery in this age group of patients.

PMID- 18085500
TI  - Open rhinoplasty in children.
AB  - Septorhinoplasty in children carries the risk of growth disturbance of the nose
      and premaxilla. The open or external approach has the advantage that the
      cartilaginous nasal skeleton remains intact. This open approach enables the
      surgeon to excise dermoid cysts and to realign lower lateral cartilages
      (unilateral cleft) without disturbing the integrity of the cartilaginous
      skeleton. In our experience, absolute indications for open rhinoplasty in
      children include dermoid cyst, cleft lip nose, and septal abscess. Relative
      indications include septal deviations causing severe nasal airway obstruction and
      or progressive distortion of the nose. In this article, we discuss the
      indications, advantages, disadvantages, and operative technique of open
      rhinoplasty in children. Our indications for open rhinoplasty in children and
      some selected cases are illustrated.

PMID- 18085501
TI  - Age at diagnosis of type 1 diabetes and the effect of immunomodulatory therapies
      on residual beta cell function.

PMID- 18085502
TI  - Treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a
      placebo-controlled double-blind clinical trial.
AB  - Many studies have found clinical and metabolic alterations in subclinical
      hypothyroidism, however, there are disagreements about the benefits of
      levothyroxine therapy. The objective of the present study was to analyze the
      effects of 6 months of treatment on the lipid profile of patients with
      subclinical hypothyroidism. A randomized double blind, placebo-controlled
      clinical assay was conducted. Sixty patients were enrolled in stratified random
      allocation by TSH levels that generated similar groups in average: free thyroxine
      levels, lipid levels, age, clinical score, and sedentary. At 6 months, 18
      patients in the levothyroxine and 20 in the placebo group were reevaluated and a
      fall in all atherogenic lipid variables was observed with treatment. The TC and
      LDL-c variations (-22.6+/-37.2 and -18.5+/-34.6 mg/dl, respectively) in the group
      that received LT4 were statistically different (p=0.023 and p=0.012) from those
      occurring in the placebo group (+7.3+/-37.1 and +14.7+/-40.6 mg/dl). Baseline
      characteristics associated with better improvement in the levels of TC and LDL-c
      were the presence of TPO-Ab, TSH levels >8.0 microUI/ml, Body Mass Index >or=25
      kg/m2, and the presence of menopause. We concluded that treatment with dose
      adjusted levothyroxine reduced atherogenic lipid levels in some patients. Further
      studies to determine the effects of LT4 replacement in specific subgroups of SH
      patients are still necessary, especially in patients with TSH <8.0 microUI/ml.

PMID- 18085503
TI  - Prevention of insulin resistance by ingesting aqueous extract of Ocimum sanctum
      to fructose-fed rats.
AB  - The study was aimed to examine if oral administration of the aqueous extract of
      the whole plant OCIMUM SANCTUM (OS) protects against the development of insulin
      resistance in fructose fed rats. Male Wister rats were randomly divided into four
      groups of eight animals each: group-S (starch diet), group-F (fructose diet),
      group-F+OS (fructose diet along with OCIMUM SANCTUM extract at a dose of 200
      mg/kg), group-S+OS (starch diet along with OCIMUM SANCTUM). During the
      experimental period of 60 days body weight, plasma glucose, insulin, and
      triglycerides were measured at an interval of 15 days. Insulin sensitivity was
      assessed at the end of experimental period by measuring glucose-insulin index,
      which is the product of the areas under the curve of glucose and insulin during
      oral glucose tolerance test. The nontoxic nature of OS was revealed by unaltered
      body weight, plasma glucose, insulin, and triglyceride levels in group-S+OS when
      compared with group-S. A significant gain in body weight, hyperglycemia,
      hyperinsulinemia, hypertriglyceridemia, and insulin resistance were observed in
      group-F when compared with group-S. OS treatment prevented the observed fructose
      induced alterations in group-F+OS. In conclusion, our results suggests that oral
      administration of OS aqueous extract could delay the development of insulin
      resistance in rats and may be used as an adjuvant therapy for treating diabetic
      patients with insulin resistance.

PMID- 18085504
TI  - Biarticular leg muscles and links to running economy.
AB  - Relationships between an index of running economy (VO2 per distance) and the
      temporal electromyographic characteristics of leg muscles were quantified in
      female runners. Sixteen women performed a 30-min treadmill run at a speed
      designed to elicit a hard rating of perceived of exertion. Near the end of the
      run, oxygen uptake, video, and electromyographic data were collected
      simultaneously. Measures of muscle on-time durations, and on-time coactivation
      durations were calculated from the following muscles: gastrocnemius, vastus
      lateralis, rectus femoris, and biceps femoris. Nonparametric correlations between
      VO2 per distance and temporal electromyographic data were evaluated. Greater on
      time duration of rectus femoris during stance, and greater on-time coactivation
      duration of rectus femoris-gastrocnemius during stance were significantly
      associated with more economical runners (i.e., lower VO2 per distance). The
      coactivation of biarticular leg muscles during stance is clearly linked to
      running economy and this control strategy may elicit greater elastic energy
      return.

PMID- 18085505
TI  - Control of pore size and structure of tissue engineering scaffolds produced by
      supercritical fluid processing.
AB  - Tissue engineering scaffolds require a controlled pore size and structure to host
      tissue formation. Supercritical carbon dioxide (scCO2) processing may be used to
      form foamed scaffolds in which the escape of CO2 from a plasticized polymer melt
      generates gas bubbles that shape the developing pores. The process of forming
      these scaffolds involves a simultaneous change in phase in the CO2 and the
      polymer, resulting in rapid expansion of a surface area and changes in polymer
      rheological properties. Hence, the process is difficult to control with respect
      to the desired final pore size and structure. In this paper, we describe a
      detailed study of the effect of polymer chemical composition, molecular weight
      and processing parameters on final scaffold characteristics. The study focuses on
      poly(DL-lactic acid) (PDLLA) and poly(DL-lactic acid-co-glycolic acid) (PLGA) as
      polymer classes with potential application as controlled release scaffolds for
      growth factor delivery. Processing parameters under investigation were
      temperature (from 5 to 55 degrees C) and pressure (from 60 to 230 bar). A series
      of amorphous PDLLA and PLGA polymers with various molecular weights (from 13 KD
      to 96 KD) and/or chemical compositions (the mole percentage of glycolic acid in
      the polymers was 0, 15, 25, 35 and 50 respectively) were employed. The resulting
      scaffolds were characterised by optical microscopy, scanning electron microscopy
      (SEM), and micro X-ray computed tomography (microCT). This is the first detailed
      study on using these series polymers for scaffold formation by supercritical
      technique. This study has demonstrated that the pore size and structure of the
      supercritical PDLLA and PLGA scaffolds can be tailored by careful control of
      processing conditions.

PMID- 18085506
TI  - In vitro comparison of human fibroblasts from intact and ruptured ACL for use in
      tissue engineering.
AB  - The present study compares fibroblasts extracted from intact and ruptured human
      anterior cruciate ligaments (ACL) for creation of a tissue engineered ACL
      construct, made of porcine small intestinal submucosal extracellular matrix (SIS
      ECM) seeded with these ACL cells. The comparison is based on histological,
      immunohistochemical and RT-PCR analyses. Differences were observed between cells
      in a ruptured ACL (rACL) and cells in an intact ACL (iACL), particularly with
      regard to the expression of integrin subunits and smooth muscle actin (SMA).
      Despite these differences in the cell source, both cell populations behaved
      similarly when seeded on an SIS-ECM scaffold, with similar cell morphology,
      connective tissue organization and composition, SMA and integrin expression. This
      study shows the usefulness of naturally occurring scaffolds such as SIS-ECM for
      the study of cell behaviour in vitro, and illustrates the possibility to use
      autologous cells extracted from ruptured ACL biopsies as a source for tissue
      engineered ACL constructs.

PMID- 18085507
TI  - Simultaneous determination of blood glucose and isoleucine levels in rats after
      chronic alcohol exposure by microwave-assisted derivatization and isotope
      dilution gas chromatography/mass spectrometry.
AB  - Blood glucose and isoleucine are two biomarkers of chronic alcohol exposure.
      Simultaneous determination of blood glucose and isoleucine levels helps to
      illuminate the influence of alcohol on the metabolism of glucose and amino acids.
      The most accurate method for the detection of serum glucose is isotope dilution
      gas chromatography/mass spectrometry (ID GC/MS). In this study, a rapid, simple
      and sensitive technique was developed for the quantitative analysis of glucose
      and isoleucine in rats after chronic alcohol exposure by microwave-assisted
      derivatization (MAD) and ID GC/MS. Serum glucose and isoleucine were rapidly
      derivatized by N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) with microwave
      irradiation, and the trimethylsilyl derivatives were analyzed by GC/MS. This
      technique was used to demonstrate that pyrroloquinoline quinone (PQQ), a non
      covalently bound prosthetic group in some quinoproteins involved in the
      metabolism of some sugar or alcohol, could reverse alcohol exposure induced
      glucose elevation. On the other hand, it did not affect the metabolism of
      isoleucine whose level was elevated along with serum glucose. The combination of
      MAD and ID GC/MS has been shown to be an accurate, rapid, simple and sensitive
      method for the quantification of glucose and isoleucine in serum samples.

PMID- 18085508
TI  - Evaluation of boldenone formation and related steroids transformations in veal
      faeces by liquid chromatography/tandem mass spectrometry.
AB  - It is established that bovine urine can result positive for boldenone and
      androstadienedione in consequence of faecal contamination. The simple transfer of
      steroids to urine is one minor aspect of faecal contamination. A high de novo
      production of steroids in faeces after deposition and in faeces-contaminated
      urine is almost certainly due to microbial activity, although the precursor
      compounds and transformations leading to the presence of these illegal steroids
      are unclear. We developed a simple in vitro method - incubation of faecal matter
      suspended in 0.9% saline - to induce steroid transformations in faeces, and
      analyzed the products by liquid chromatography/tandem mass spectrometry, without
      the need for prior extraction. Norethandrolone was the internal standard. The
      linearity (R(2): 0.987-0.999), sensitivity (LODs: 0.3 to 1.0 ng/mL; LOQs: 1.0 to
      3.0 ng/mL), precision (intra-day CVs: 2.6-8.2; inter-day CVs: 4.5-11.5) and
      accuracy (percentage recovery: 89-120%) were calculated for the studied steroids.
      Androstenedione, androstadienedione, alpha- and beta-boldenone, testosterone and
      epitestosterone transformations were investigated. Mutual interconversion of
      steroids was observed, although 17beta-hydroxy steroids had low stability
      compared with 17alpha-hydroxy and 17-keto steroids. The results suggest that this
      simple in vitro system may be an effective way of studying hormone
      transformations in faeces and, after analogue studies, in faeces-contaminated
      urine.

PMID- 18085509
TI  - Structuring and interactions of human beta-defensins 2 and 3 with model
      membranes.
AB  - beta-Defensins play an important role in both innate and adaptive immunity,
      displaying a direct anti-microbial activity against a wide variety of micro
      organisms as well as interesting immuno-modulatory effects on host cells.
      Interaction with biological membranes appears to be a central theme in modulating
      these activities, leading to different consequences such as membrane lysis,
      translocation into the cytoplasm or transfer to a receptor. We have investigated
      the structuring of human beta-defensins (hBD2 and hBD3) and rationally designed
      variants, in relation to their interactions with real and model membranes.
      Biophysical methods, such as circular dichroism (CD), transmission or reflection
      IR and dye release were used to probe their structure/activity in the presence of
      model membranes, while fluorimetric and flow cytometric assays were used to
      investigate the effects on prokaryotic cells. Our results indicate that
      structural features, such as the helical N-terminal domains and oligomerisation
      at the membrane surface, may modulate the efficiency of membrane insertion and
      selectivity for microbial or host-cell membranes. We propose that both peptides
      interact with membranes as extended beta-sheet platforms that present amphipathic
      helices for insertion into the lipid bilayer.

PMID- 18085510
TI  - Influence of measured and simulated basis sets on metabolite concentration
      estimates.
AB  - By quantification of brain metabolites, localized brain proton MRS can non
      invasively provide biochemical information from distinct regions of the brain.
      Quantification of short-TE signals is usually based on a metabolite basis set.
      The basis set can be obtained by two approaches: (1) by measuring the signals of
      metabolites in aqueous solution; (2) by quantum-mechanically simulating the
      theoretical metabolite signals. The purpose of this study was to compare the
      effect of these two approaches on metabolite concentration estimates. Metabolite
      concentrations were quantified with the QUEST method, using both approaches. A
      comparison was performed with the aid of Monte Carlo studies, by using signals
      simulated from both basis sets. The best results were obtained when the basis set
      used for the fit was the same as that used to simulate the Monte Carlo signals.
      This comparison was also performed using in vivo short-TE signals acquired at 7 T
      from the central region of rat brains. The concentration estimates, with
      confidence intervals, obtained using both basis sets were in good agreement with
      values from the literature. The in vivo study showed that, in general, the
      differences between the estimates obtained with the two basis sets were not
      statistically significant or scientifically important. Consequently, a simulated
      basis set can be used in place of a measured basis set.

PMID- 18085511
TI  - High-performance liquid chromatography/electrospray ionization tandem mass
      spectrometry for characterization of enzymatic degradation of 2,2'-bis(2
      oxazoline)-linked poly-epsilon-caprolactone.
AB  - This paper describes a straightforward and rapid on-line characterization using
      high-performance liquid chromatography/electrospray ionization tandem mass
      spectrometry (HPLC/ESI-MS(n)) of the enzymatic degradation products of 2,2'-bis(2
      oxazoline)-linked poly-epsilon-caprolactone (PCL-O). These new PCL-O polymers are
      expected to be used in a variety of pharmaceutical and biomedical applications
      since they are degraded enzymatically by surface erosion. PCL-O was polymerized
      in a three-step reaction and characterized by (1)H-NMR and size-exclusion
      chromatography (SEC). Solvent cast polymer films were exposed to enzymatic
      degradation in phosphate buffer (pH 7.5, 1% pancreatin). The enzymatic
      degradation of the polymer produced a wide variety of water-soluble oligomers
      which were separated and identified by HPLC/ESI-MS(n). Optimization of the
      gradient HPLC method resulted in effective separation of the oligomers.
      Furthermore, specific structures of the oligomers were clearly identified by
      tandem mass spectrometry. According to these results, ester bonds seem to be most
      sensitive to enzymatic degradation and, correspondingly, pancreatic lipase seems
      to be mainly responsible for the enzymatic erosion of the PCL-O films. This novel
      mass spectrometric method provides important knowledge about the enzymatic
      degradation process and structure of the polymer which is difficult to ascertain
      by other conventional methods.

PMID- 18085512
TI  - Quantitation of 5-fluorouracil (5-FU) in human plasma by liquid
      chromatography/electrospray ionization tandem mass spectrometry.
AB  - 5-Fluorouracil (5-FU) has long had a place in the treatment of many malignancies.
      5-FU plasma concentrations have been correlated with toxicity and efficacy, and
      therapeutic drug monitoring has been reported to result in an improved
      response/toxicity balance. We report validation, according to FDA guidelines, of
      a hydrophilic interaction chromatography (HILIC) liquid chromatography/tandem
      mass spectrometry (LC/MS/MS) assay for the sensitive, accurate and precise
      quantitation of 5-FU in human plasma. The assay employed an isotopically labeled
      5-FU internal standard and ethyl acetate extraction. Separation was achieved with
      an amino column and an isocratic mobile phase of 0.1% formic acid in
      acetonitrile/water (97:3, v/v), followed by a wash. Detection consisted of
      electrospray, negative-mode ionization tandem mass spectrometry in the multiple
      reaction monitoring (MRM) mode. The accuracy was 96.0-102.2%, and precision was
      2.1-7.5% in the concentration range of 10-10 000 ng/mL. Recovery from plasma was
      46.0-72.6%, and ion suppression was 9.8-25.7%. Plasma freeze/thaw stability was
      87.5-104.3%, and stability for 4 h at room temperature was 98.7-100.0%. This
      assay is currently being used to quantitate 5-FU in human plasma samples.

PMID- 18085513
TI  - Fuscopeptins, antimicrobial lipodepsipeptides from Pseudomonas fuscovaginae, are
      channel forming peptides active on biological and model membranes.
AB  - FP-A and FP-B are LDPs produced by the plant pathogen Pseudomonas fuscovaginae.
      As expected from their primary structure, they shared a similar mechanism of
      action with the better characterized SPs, synthesized by strains of Pseudomonas
      syringae pv. syringae. Indeed, they displayed hemolytic activity on human
      erythrocytes and were able to induce calcein release from LUVs: the effect was
      dependent on the concentration of the FPs and the lipid composition of the
      liposome and, in particular, it increased with the SM content of the membrane.
      The permeabilizing activity was further investigated on PLMs. FPs were able to
      open pores on pure POPC membranes. Pore opening was strongly voltage dependent:
      by switching the potential from negative to positive values, an increase in the
      absolute amplitude of transmembrane current was induced with simultaneous closure
      of pores. In 0.1 M KCl both FPs' pores had a conductance of 4 and 9 pS at - 140
      mV and + 140 mV, respectively. Studies on ion selectivity indicated that FPs
      formed cation-selective channels.

PMID- 18085514
TI  - (1)H NMR metabolite profiling of feces as a tool to assess the impact of
      nutrition on the human microbiome.
AB  - Current research increasingly recognizes the human gut microbiome as a
      metabolically versatile biological 'digester' that plays an essential role in
      regulating the host metabolome. Gut microbiota recover energy and biologically
      active molecules from food that would otherwise be washed out of the intestinal
      tract without benefit. In this study, a protocol for NMR-based metabolite
      profiling has been developed to access the activity of the microbiome. The
      physicochemical properties of fecal metabolites have been found to strongly
      affect the reproducibility and coverage of the profiles obtained. Metabolite
      profiles generated by water and methanol extraction of lyophilized feces are
      reproducible and comprise a variety of different compounds including, among
      others, short-chain fatty acids (e.g. acetate, propionate, butyrate, isobutyrate,
      isovalerate, malate), organic acids (e.g. succinate, pyruvate, fumarate,
      lactate), amino acids, uracil, trimethylamine, ethanol, glycerol, glucose,
      phenolic acids, cholate, and lipid components. The NMR profiling approach was
      validated on fecal samples from a double-blinded, placebo-controlled, randomized
      cross-over study, in which healthy human subjects consumed a placebo and either a
      grape juice extract or a mix of grape juice and wine extract over a period of 4
      weeks, each. The considerable inter- and intra-individual variability observed
      originates in the first instance from variable metabolite concentrations rather
      than from variable metabolite compositions, suggesting that different colonic
      flora share general biochemical characteristics metabolizing different substrates
      to specific metabolic patterns. Whereas the grape juice extract did not induce
      changes in the metabolite profiles as compared with the placebo, the mixture of
      grape juice and wine extract induced a reduction in isobutyrate, which may
      indicate that polyphenols are able to modulate the microbial ecology of the gut.

PMID- 18085515
TI  - Solid-phase synthesis of tailed cyclic RGD peptides using glutamic acid:
      unexpected glutarimide formation.
AB  - To provide multiple conjugating sites on cyclic peptides for their increasing
      biomedical applications, a tailed cyclic RGD peptide, c[RGDfE(GGGKK-NH(2))] was
      designed with c(RGDfE) linked through Glu to a tail consisting of a spacer of
      three Gly residues and a linker of two Lys residues. The spacer is used to
      increase the mobility and binding ability of the c(RGDfE) ligand, and the linker
      is used to proved multiple active sites for conjugating other molecules or
      biomaterials. We found that the sequence of Glu(Gly)-OAll leads to glutarimide
      formation, which disrupts the formation of cyclic RGD peptides. However, our
      results show that glutarimide formation is sequence dependent and can be
      inhibited by incorporating an amino acid like Lys(Boc) with steric hindrance from
      the protecting group. To prevent glutarimide formation, Ser(tBu) was used to
      replace the glycine in the GGG spacer adjacent to the residue of Glu, and a
      tailed cyclic RGD peptide, c[RGDfE(SGGKK-NH(2))] was successfully obtained.

PMID- 18085516
TI  - Conformation of di-n-propylglycine residues (Dpg) in peptides: crystal structures
      of a type I' beta-turn forming tetrapeptide and an alpha-helical
      tetradecapeptide.
AB  - The crystal structures of two oligopeptides containing di-n-propylglycine (Dpg)
      residues, Boc-Gly-Dpg-Gly-Leu-OMe (1) and Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala
      Leu-Dpg-Val-Ala-Leu-OMe (2) are presented. Peptide 1 adopts a type I'beta-turn
      conformation with Dpg(2)-Gly(3) at the corner positions. The 14-residue peptide 2
      crystallizes with two molecules in the asymmetric unit, both of which adopt alpha
      helical conformations stabilized by 11 successive 5 --> 1 hydrogen bonds. In
      addition, a single 4 --> 1 hydrogen bond is also observed at the N-terminus. All
      five Dpg residues adopt backbone torsion angles (phi, psi) in the helical region
      of conformational space. Evaluation of the available structural data on Dpg
      peptides confirm the correlation between backbone bond angle N-C(alpha)-C' (tau)
      and the observed backbone phi,psi values. For tau > 106 degrees, helices are
      observed, while fully extended structures are characterized by tau < 106 degrees.
      The mean tau values for extended and folded conformations for the Dpg residue are
      103.6 degrees +/- 1.7 degrees and 109.9 degrees +/- 2.6 degrees, respectively.

PMID- 18085482
TI  - Human health risk assessment for aluminium, aluminium oxide, and aluminium
      hydroxide.

PMID- 18085517
TI  - Insulin-like growth factor binding protein-5 (IGFBP-5) suppresses the
      tumourigenesis of head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a global malignancy. The insulin
      like growth factor (IGF) signalling axis plays a critical role in tumourigenesis.
      This study defined the clinical and functional roles of insulin-like growth
      factor binding protein-5 (IGFBP-5) in HNSCC. Down-regulation of IGFBP-5 mRNA
      expression was found during the progression from pre-cancer to HNSCC. The down
      regulation in HNSCC was associated with a higher propensity to nodal metastasis.
      SAS and OECM-1 are HNSCC cells that do, or do not, express IGFBP-5, respectively.
      Recombinant IGFBP-5 reduced the proliferation of OECM-1 cells and this was
      exerted mainly through blockade of the IGF pathways. Either IGFBP-5 or IGF-I
      treatment alone promoted OECM-1 migration, but a combination of treatments
      generated antagonistic effects. Overexpression of IGFBP-5 reduced the
      proliferation and anchorage-independent growth of both OECM-1 and SAS cells.
      Conversely, knockdown of IGFBP-5 expression significantly induced the
      proliferation and anchorage-independent growth of SAS cells. It also induced the
      growth of xenografted SAS tumours. SAS transfectants that expressed mutant or
      truncated IGFBP-5, which lack IGF binding activity, exhibited significantly lower
      anchorage-independent growth than vector control. This suggests that IGFBP-5
      possesses an IGF-independent suppressor function. The suppressive effects of
      IGFBP-5 on the tumourigenesis of HNSCC might be invaluable to future neoplastic
      intervention.

PMID- 18085518
TI  - On-line coupling of an ultraviolet titanium dioxide film reactor with a liquid
      chromatography/hydride generation/inductively coupled plasma mass spectrometry
      system for continuous determination of dynamic variation of hydride- and
      nonhydride-forming arsenic species in very small microdialysate samples.
AB  - We describe a method for continuously monitoring both hydride- and nonhydride
      forming arsenic species in 10-microL microdialysate samples by coupling together
      on-line high-performance liquid chromatography (HPLC), a post-column UV/TiO2 film
      reactor, and hydride generation (HG) inductively coupled plasma mass spectrometry
      (ICP-MS). To maximize the signal intensities of the desired arsenic species, we
      optimized the photocatalytic oxidation efficiency of the analyte species and used
      a rapid on-line pre-reduction process to convert the oxidized species into
      As(III) prior to HG-ICP-MS determination. The UV/nano-TiO2 film reactor was
      manufactured by coating nano-TiO2 onto the interior of a glass tube. Impregnation
      and sol-gel methods were employed to deposit the TiO2 films, and their
      effectiveness for the oxidation of organic arsenicals was compared. To enhance
      the decomposition efficiency of organic arsenicals, we investigated the effects
      of the acidity and the composition of the column effluent. Because of the
      improved HG efficiency toward the tested arsenicals and the adoption of a
      segmented flow technique to retain the peak resolution in our on-line LC-UV/nano
      TiO2 film reactor-HG-ICP-MS instrument, the detection limits for arseneous acid
      [As(III)], monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenic acid
      [As(V)], and arsenobetaine (AsB) were all in the submicrogram-per-liter range
      (based on 3 sigma) for 10-microL injections. A series of validation experiments-
      analyses of certified reference urine and rabbit serum samples--indicated that
      these methods can be applied satisfactorily to the continuous determination of
      As(III), MMA, DMA, As(V), and AsB in blood and in the extracellular space of
      target organs.

PMID- 18085519
TI  - The N-domain of angiotensin-converting enzyme specifically hydrolyzes the Arg-5
      His-6 bond of Alzheimer's Abeta-(1-16) peptide and its isoAsp-7 analogue with
      different efficiency as evidenced by quantitative matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Chronic imbalance between production and degradation of the human amyloid-beta
      peptide (Abeta) is assumed to play an important role in pathogenesis of
      Alzheimer's disease (AD). Post-translational modifications of Abeta could
      influence its interactions with specifically cleaving proteases and, therefore,
      perturb the Abeta homeostasis. The angiotensin-converting enzyme (ACE) was
      previously shown to degrade non-modified Abeta in vitro and in cells. In the
      presented work, we investigated the effect of isomerization of Asp-7, a common
      non-enzymatic age-related modification found in AD-associated Abeta species, on
      hydrolysis of Abeta by ACE. Two synthetic peptides corresponding to the Abeta
      region 1-16 with either Asp or isoAsp residues in position 7 were examined as
      monomeric soluble substrates for the N- as well as for the C-domain of ACE. The
      use of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS) coupled with the (18)O-labeled internal standard
      approach has allowed us to show that (i) the N-domain of ACE (N-ACE), but not the
      C-domain, selectively cleaves the Arg-5-His-6 bond in both peptides, and that
      (ii) N-ACE hydrolyzes the isoAsp-7 analogue more efficiently than the non
      modified one. Our results demonstrate a new endopeptidase activity of N-ACE as
      well as high preference of the domain to recognize and hydrolyze the isomerized
      Abeta species that were earlier suggested to promote AD pathogenesis. The results
      suggest the need for further analysis of biological effects of isomerized Abeta
      and its interaction with ACE in AD pathogenesis.

PMID- 18085520
TI  - The contributions of oestrogen receptor isoforms to the development of papillary
      and anaplastic thyroid carcinomas.
AB  - Oestrogen (E2) is known to promote the proliferation of thyroid papillary
      carcinoma cells (KAT5). However, the molecular mechanism responsible is not well
      understood. In the study reported herein, the localization of ER alpha (ERalpha)
      and beta (ERbeta) in KAT5 and anaplastic carcinoma cells (FRO) was studied by
      immunofluorescence staining and by immunoblotting the proteins in subcellular
      fractions. Cell proliferation and apoptosis were also determined together with
      the expression of relevant proteins. The pattern of the subcellular localization
      of ERalpha and ERbeta differed between papillary and anaplastic cancer. Upon E2
      treatment, the level of ERalpha increased in the nuclei of papillary cancer cells
      but ERbeta remained unchanged. The level of mitochondrial ERbeta surpassed that
      of ERalpha in anaplastic cancer cells. The different locations of ERalpha and
      ERbeta in KAT5 and FRO agreed with the finding that E2 promoted the proliferation
      of KAT5 but inhibited or did not affect that of FRO cells, and with the proposed
      functions of these two receptors. E2 inhibited the level of Bax in the
      mitochondria of papillary cancer, followed by a decrease of cytochrome c and/or
      apoptosis-inducing factor (AIF) release from the mitochondria into the cytosol.
      However, in anaplastic cancer, E2 promoted the expression of Bax in the
      mitochondria and the release of cytochrome c and/or AIF from mitochondria into
      the cytosol. Our results may explain the differences in epidemiology and
      responses to anti-tumour therapy between papillary and anaplastic cancer in terms
      of the subcellular localization of ER isoforms. In conclusion, the findings
      provide evidence to support the observation that E2 is an important factor in the
      development of thyroid cancer. The subcellular localization of ERalpha and ERbeta
      may account for the different pathogenesis of thyroid papillary and anaplastic
      cancers.

PMID- 18085521
TI  - Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular
      epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa
      with angiomyolipoma.
AB  - Perivascular epithelioid cell tumours (PEComas) are a family of tumours including
      classic angiomyolipoma, lymphangioleiomyomatosis, and clear epithelioid cell
      tumours reported under a variety of names such as epithelioid angiomyolipoma,
      pulmonary and extrapulmonary clear cell sugar tumour, and PEComa. Our previous
      comparative genomic hybridization study of PEComas demonstrated recurrent
      chromosomal aberrations including deletions on chromosome 16p, where the TSC2
      gene is located. In this study, we focused on the alteration of chromosome 16p,
      including TSC2. We collected ten sporadic and two tuberous sclerosis complex
      associated PEComas, as well as 14 sporadic classic hepatic and renal
      angiomyolipomas (AMLs) as controls. We used 16 microsatellite markers distributed
      along chromosome 16p to test for allelic imbalances on chromosome 16p and at
      TSC2, and two markers for TSC1. Furthermore, we carried out immunohistochemical
      staining for phospho-p706K, phospho-AKT, and phospho-S6 to evaluate the effect of
      TSC2 alterations on the mTOR signalling pathway. Loss of heterozygosity (LOH) was
      found in 11 PEComas and involved the region of the TSC2 locus in seven. Six
      classic angiomyolipomas had allelic changes at chromosome 16p. Microsatellite
      instability was detected in two PEComas. The incidence of genetic aberrations was
      significantly higher in the PEComa group. Only one PEComa showed LOH at the TSC1
      locus. Eleven PEComas and 13 AMLs revealed elevated phospho-p70S6K accompanied by
      reduced phospho-AKT. Five PEComas and eight classic angiomyolipomas were positive
      for phospho-S6. The phosphorylation profile indicates functional activation of
      the mTOR pathway through a disrupted TSC1/2 complex. Our observations of frequent
      deletion of TSC2 and the mTOR signalling pathway provide evidence that the
      oncogenetic lineage of PEComa, as a distinct TSC2-linked neoplasm, is similar to
      that of angiomyolipoma.

PMID- 18085522
TI  - ALT-associated promyelocytic leukaemia body (APB) detection as a reproducible
      tool to assess alternative lengthening of telomere stability in liposarcomas.
AB  - Most cancers maintain telomeres by activating telomerase, but a significant
      minority, mainly of mesenchymal origin, utilize an alternative lengthening of
      telomeres (ALT) mechanism. We previously showed the presence of ALT, as detected
      by ALT-associated promyelocytic leukaemia bodies (APBs) by combined promyelocytic
      leukaemia immunofluorescence and telomere fluorescence-in situ hybridization, in
      approximately 25% of frozen specimens obtained from adult patient liposarcomas
      and proved that ALT negatively affects patient prognosis. In the present study,
      we assessed the reproducibility of APB detection on frozen versus formalin-fixed,
      paraffin-embedded specimens from the same liposarcoma specimens and investigated
      the eventual stability of ALT in 103 different lesions from 40 adult patients
      followed during their disease. Irrespective of liposarcoma subtype, we (1)
      confirmed the presence of ALT in 21.4% of tumours; (2) demonstrated the
      reliability of ALT-associated promyelocytic leukaemia body detection in formalin
      fixed, paraffin-embedded sections (with qualitative concordance between matched
      frozen and formalin-fixed, paraffin-embedded samples in 29/30 specimens, and high
      quantitative agreement, as indicated by a Spearman correlation coefficient of
      0.85); and (3) suggested the stability of ALT status during disease evolution,
      since the ALT mechanism was never acquired in the 29 patients with initially ALT
      negative lesions and lost over time in only two of 11 patients with initially ALT
      positive liposarcomas. In conclusion, these results confirm the possibility of
      investigating the ALT mechanism in archival specimens to obtain biologically
      relevant information on liposarcoma progression, even when the primary lesion is
      not available.

PMID- 18085523
TI  - Transcription factor SOX-5 enhances nasopharyngeal carcinoma progression by down
      regulating SPARC gene expression.
AB  - Nasopharyngeal carcinoma (NPC) is prevalent in south-eastern Asia, and its
      tumourigenesis is rather complex. The purpose of this research was to identify
      the pivotal genes that may be altered during the early stage of NPC progression.
      Eleven genes were selected by comparative microarray analysis of NPC versus
      normal nasomucosal cells. The expression of SPARC (secreted protein, acidic,
      cysteine-rich) was statistically significantly down-regulated in NPC cells. In
      exploring the mechanism underlying the decreased transcription of SPARC in NPC
      cells, we found that the transcription factor SRY (sex-determining region Y)-box
      5 (SOX-5) is up-regulated in NPC cells. RNA interference of SOX-5 by short
      hairpin RNA (shRNA) in NPC cells caused a dramatic increase in SPARC and
      chromosome immunoprecipitation assay showed that SOX-5 can bind directly to the
      SPARC promoter, suggesting that SOX-5 acts as a key transcriptional repressor of
      SPARC. We further demonstrated that shRNA knockdown of SOX-5 suppressed the
      proliferation of NPC cells, as well as their migratory ability, which was also
      observed when SPARC was over-expressed in NPC cells. Alternatively, blocking
      SPARC with an antagonistic antibody reversed the effects of SOX-5 knockdown. In
      66 NPC patients, over-expression of SOX-5 in tumour cells correlated clinically
      with poor survival. Our study suggests that SOX-5 transcriptionally down
      regulates SPARC expression and plays an important role in the regulation of NPC
      progression. SOX-5 is a potential tumour marker for poor NPC prognosis.

PMID- 18085524
TI  - Re-emerging conceptual integration: commentary on Berkowitz's "on the
      consideration of automatic as well as controlled psychological processes in
      aggression".
AB  - In recent decades, researchers in various areas of psychology have challenged the
      claims of a single mode of information processing, and developed dual-process
      models of social behaviors. Although these theories differ on a number of
      dimensions, they all share the basic assumption that two different modes of
      information processing operate in making decision and copying behavior. In
      essence, the common distinction in these perspectives is between controlled vs.
      automatic, conscious vs. unconscious, and affective vs. cognitive modes of
      processing. The purpose of Berkowitz's article is to go beyond the notion of
      automatic processes in order to use classic notions of conditioning and
      displacement to explain aggressive behavior. I assert that an explanatory
      framework for psychology of aggression must be anchored not only in the new but
      also classic theoretical paradigms. However, progress in psychology does not rest
      solely on the accumulation of theoretical insights. It demands a large body of
      empirical facts, with attention to incongruities, discordances, and conceptual
      clarifications.

PMID- 18085525
TI  - Effects of psychopathy traits on unprovoked aggression.
AB  - Research has demonstrated that risk of violent behavior is high in individuals
      who display psychopathic traits. However, prediction of general aggression, and
      in particular unprovoked aggression, in nonforensic men who possess such traits
      has received little experimental attention to date. This study examined the role
      of psychopathic traits in the prediction of unprovoked aggression in a
      nonforensic sample. One hundred and five men completed the Levenson Self-Report
      Psychopathy Scales and competed in a sham aggression paradigm. These men were
      identified as unprovoked aggressors, provoked aggressors, and provoked
      nonaggressors contingent on their responses to the experimental paradigm.
      Findings indicated that men with high levels of psychopathic traits had a 30%
      greater probability of becoming aggressive in the absence of provocation relative
      to those with lower psychopathic traits. Results also indicated that unprovoked
      aggressors evinced more general aggression when provocation was initiated.
      Findings are discussed in terms of the importance of trait-based risk factors in
      the prediction of seemingly random, unprovoked aggression.

PMID- 18085526
TI  - The evolution of female mole ovotestes evidences high plasticity of mammalian
      gonad development.
AB  - Previous studies of the reproductive biology and genetics of European moles
      (Talpa spp.) showed that all females of these species have ovotestes (gonads with
      testicular and ovarian tissue) instead of normal ovaries, a unique specialization
      among mammals. Females are fertile as their ovarian tissue is fully functional.
      Testicular tissue is abnormal and sterile, but produces high levels of
      testosterone. This phenomenon also characterizes other talpid species from Europe
      and North America. To study the origin of this singular reproductive
      specialization, we examined the gonads of several female specimens belonging to
      two critical taxa. Although large Japanese moles (Mogera wogura) posses
      ovotestes, greater Japanese shrew moles (Urotrichus talpoides) are characterized
      by normal ovaries. The results fit parsimoniously with a recent phylogenetic
      study that places Urotrichus relatively basal in the talpid tree and separate
      from the American shrew mole. Parsimony reconstruction on alternative
      phylogenetic hypotheses clearly indicates that reversal(s) must have occurred and
      suggests that a relatively simple genetic mechanism must be associated with the
      evolution of female hermaphroditism in moles.

PMID- 18085527
TI  - Choroid plexus cyst, intracardiac echogenic focus, hyperechogenic bowel and
      hydronephrosis in screening for trisomy 21 at 11 + 0 to 13 + 6 weeks.
AB  - OBJECTIVES: To investigate the potential value of choroid plexus cyst,
      intracardiac echogenic focus, hydronephrosis and hyperechogenic bowel as markers
      of trisomy 21 at 11 + 0 to 13 + 6 weeks. METHODS: We examined three-dimensional
      volumes from 228 fetuses with trisomy 21 and 797 chromosomally normal fetuses at
      11 + 0 to 13 + 6 weeks of gestation. We looked for choroid plexus cysts with a
      minimum diameter of 1.5 mm, intracardiac echogenic focus, hydronephrosis with a
      minimum anteroposterior diameter of the pelvis of 1.5 mm and hyperechogenic
      bowel. RESULTS: The prevalence of intracardiac echogenic focus, hydronephrosis
      and hyperechogenic bowel was significantly higher in trisomy 21 than in normal
      fetuses (9.6% vs. 1.5%, 17.1% vs. 5.3% and 11.4% vs. 2.4%, respectively). There
      was no significant difference between the two groups in the prevalence of choroid
      plexus cysts (7.5% vs. 5.0%). There were no significant differences in crown-rump
      length or nuchal translucency thickness in either chromosomally normal or trisomy
      21 fetuses between those with and those without any one of the markers.
      CONCLUSIONS: At 11 + 0 to 13 + 6 weeks the prevalence of intracardiac echogenic
      focus, hydronephrosis and hyperechogenic bowel is higher in trisomy 21 than in
      chromosomally normal fetuses. As there is no significant association between the
      presence of these markers and nuchal translucency thickness, they could be
      included in the assessment of risk to improve accuracy of screening.

PMID- 18085528
TI  - Antitumor activity of 3,5,4'-trimethoxystilbene in COLO 205 cells and xenografts
      in SCID mice.
AB  - Resveratrol (R-3), a trihydroxy trans-stilbene from grape, inhibits multistage
      carcinogenesis in animal models. Here we report that 3,5,4'-trimethoxystilbene
      (MR-3), the permethylated derivative of R-3 was more potent against the growth of
      human cancer cells (HT-29, PC-3, COLO 205) with estimated IC(50) values of
      81.31,42.71, and 6.25 microM, respectively. We further observed that MR-3 induced
      apoptosis in COLO 205 cells through modulation of mitochondrial functions
      regulated by reactive oxygen species (ROS). ROS generation occurs in the early
      stages of MR-3-induced apoptosis, preceding cytochrome-c release, caspase
      activation, and DNA fragmentation. Significant therapeutic effects were
      demonstrated in vivo by treating severe combined immune deficiency (SCID) mice
      bearing COLO 205 tumor xenografts with MR-3 (50 mg/kg ip). Assays on DNA
      fragmentation and caspase activation were performed and demonstrated that
      apoptosis occurred in tumor tissues treated with MR-3. The appearance of
      apoptotic cells, as shown by Hematoxylin and Eosin (H&E) staining, and an
      increase in p21 and decrease in proliferating cell nuclear antigen (PCNA) protein
      by immuno-histochemistry were observed in tumor tissues under MR-3 treatment. Our
      study identifies the novel mechanisms of the antitumor effects of MR-3 and
      indicates that these results may have significant applications for cancer
      chemotherapy.

PMID- 18085529
TI  - Differential effects of black raspberry and strawberry extracts on BaPDE-induced
      activation of transcription factors and their target genes.
AB  - The chemopreventive properties of edible berries have been demonstrated both in
      vitro and in vivo, however, the specific molecular mechanisms underlying their
      anti-cancer effects are largely unknown. Our previous studies have shown that a
      methanol extract fraction of freeze-dried black raspberries inhibits benzoapyrene
      (BaP)-induced transformation of Syrian hamster embryo cells. This fraction also
      blocks activation of activator protein-1 (AP-1) and nuclear factor kappaB (NF
      kappaB) induced by benzoapyrene diol-epoxide (BaPDE) in mouse epidermal JB6 Cl 41
      cells. To determine if different berry types exhibit specific mechanisms for
      their anti-cancer effects, we compared the effects of extract fractions from both
      black raspberries and strawberries on BaPDE-induced activation of various
      signaling pathways in Cl 41 cells. Black raspberry fractions inhibited the
      activation of AP-1, NF-kappaB, and nuclear factor of activated T cells (NFAT) by
      BaPDE as well as their upstream PI-3K/Akt-p70(S6K) and mitogen-activated protein
      kinase pathways. In contrast, strawberry fractions inhibited NFAT activation, but
      did not inhibit the activation of AP-1, NF-kappaB or the PI-3K/Akt-p70(S6K) and
      mitogen-activated protein kinase pathways. Consistent with the effects on NFAT
      activation, tumor necrosis factor-alpha (TNF-alpha) induction by BaPDE was
      blocked by extract fractions of both black raspberries and strawberries, whereas
      vascular endothelial growth factor (VEGF) expression, which depends on AP-1
      activation, was suppressed by black raspberry fractions but not strawberry
      fractions. These results suggest that black raspberry and strawberry components
      may target different signaling pathways in exerting their anti-carcinogenic
      effects.

PMID- 18085530
TI  - Neoplastic conversion of human colon smooth muscle cells: No requirement for
      telomerase.
AB  - The role of telomerase as an essential requirement for the neoplastic conversion
      of human cells has been controversial. In the model of conversion of normal human
      cells to cancer cells by the combination of simian virus 40 (SV40) early region
      genes and oncogenic Ras (H-Ras(G12V)), telomerase (hTERT) was originally
      described as essential in conjunction with these other genes. Here we used
      primary cultures of colon smooth muscle cells isolated from surgical specimens.
      SV40 large T antigen (TAg) and oncogenic Ras(G12V) were introduced into the cells
      by retroviral transduction and cells were rapidly transplanted into the subrenal
      capsule space in immunodeficient mice, without selection in culture. Malignant
      tumors were formed from transduced cells. Extensive invasion into the kidney
      occurred even when tumors were small; in contrast, at the same tumor size,
      oncogene-expressing fibroblasts did not show much invasion. Increased
      invasiveness was also observed in vitro. However, cells in these cancers showed
      morphological evidence of crisis, consistent with their lack of telomerase. These
      experiments on human colon smooth muscle cells support the concept that Ras(G12V)
      and SV40 TAg form a minimal set of genes that can convert normal human cells to
      cancer cells without a requirement for hTERT.

PMID- 18085531
TI  - Attenuation of DNA damage-induced p53 expression by arsenic: a possible mechanism
      for arsenic co-carcinogenesis.
AB  - Inhibition of DNA repair processes has been suggested as one predominant
      mechanism in arsenic co-genotoxicity. However, the underlying mode of action
      responsible for DNA repair inhibition by arsenic remains elusive. To further
      elucidate the mechanism of repair inhibition by arsenic, we examined the effect
      of trivalent inorganic and methylated arsenic metabolites on the repair of
      benzo(a)pyrene diol epoxide (BPDE)-DNA adducts in normal human primary
      fibroblasts and their effect on repair-related protein expression. We observed
      that monomethylarsonous acid (MMA(III)) was the most potent inhibitor of the DNA
      repair. MMA(III) did not change the expression levels of some key repair proteins
      involved upstream of the dual incision in the global nucleotide excision repair
      (NER) pathway, including p48, XPC, xeroderma pigmentosum complementation group A
      (XPA), and p62-TFIIH. However, it led to a marked impairment of p53 induction in
      response to BPDE treatment. The abrogated p53 expression translated into reduced
      p53 DNA-binding activity, suggesting a possibility of downregulating downstream
      repair genes by p53. A p53-null cell line failed to exhibit the inhibitory effect
      of MMA(III) on NER, implicating a role for p53 in the NER inhibition by MMA(III).
      Further investigation revealed that MMA(III) dramatically inhibited p53
      phosphorylation at serine 15, implying that MMA(III) destabilized p53 by
      inhibiting its phosphorylation. Because p53 is required for proficient global
      NER, our data suggest that arsenic inhibits NER through suppressing p53 induction
      in response to DNA damage in cells with normal p53 gene expression.

PMID- 18085532
TI  - Reciprocal influences between maternal discipline techniques and aggression in
      children and adolescents.
AB  - Most studies assessing the link between parental discipline and child aggression
      have focused primarily on discipline as a cause and aggression as an outcome. In
      addition to the pathway from discipline to aggression, however, aggressive
      behavior on the part of the child may lead to future use of discipline by the
      parent. In this study, structural equation modeling was used to assess reciprocal
      influences over time between a mothers' use of discipline and aggression in
      children. Data were drawn from the Springfield Child Development Project, a
      longitudinal study of middle childhood and adolescence, focusing on antecedents
      of aggression. The original sample consisted of 440 mother-child dyads living in
      the city of Springfield, MA. Children in the sample were between 7 and 14 years
      of age at the first data collection period and between 12 and 19 years of age at
      the final data collection period. Four hypotheses were tested: (1) a mother's use
      of aggressive discipline predicts an increase in later child aggression, (2)
      child aggression predicts an increase in later use of aggressive discipline, (3)
      the use of reasoning predicts a decrease in later child aggression, and (4) child
      aggression predicts an increase in later use of reasoning. All hypotheses except
      number 3 were supported to some degree. Results suggest that children's early
      aggressive behavior leads to an increase in their mothers' use of both reasoning
      and aggressive discipline; in turn, increased use of aggressive discipline leads
      to an increase in aggression during both childhood and adolescence.

PMID- 18085537
TI  - Ion-conduction pathways in self-organised ureidoarene-heteropolysiloxane hybrid
      membranes.
AB  - This paper reports on hybrid organic-inorganic dense membrane materials in which
      protons and ions are envisioned to diffuse along the hydrophilic pathways. The
      hierarchical generation of functional hybrid materials was realised in two steps.
      First, the self-assembling properties of 3-(ureidoarene)propyltriethoxysilane
      compounds 1-5 in aprotic solvents were determined, revealing the formation of
      supramolecular oligomers. Compounds 1-5 generate organogels in chloroform or in
      acetone, leading in a second sol-gel transcription step to hybrid membrane
      materials on a nanoscopic scale. The crystal structures of 1-5 indicate that the
      arrangement is mainly defined by periodic parallel sheets, resulting from the
      alignment of hydrophobic organic and inorganic silica layers. Hybrid materials MB
      1-MB 4, with a similar lamellar structure, define particularly attractive
      functional transport devices; they are oriented along the organic layers and
      sandwiched between the two siloxane layers. These systems have been employed
      successfully to design solid dense membranes and illustrate how the self
      organised hybrid materials perform interesting and potentially useful functions.

PMID- 18085536
TI  - 1,1-bis(3'-indolyl)-1-(p-substituted phenyl)methanes decrease mitochondrial
      membrane potential and induce apoptosis in endometrial and other cancer cell
      lines.
AB  - 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes, containing p-t-butyl (DIM-C
      pPhtBu) and phenyl (DIM-C-pPhC(6)H(5)) substituents, are peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists; however, DIM-C-pPhtBu-induced
      growth inhibition and cell death in human HEC1A endometrial cancer cells is
      PPARgamma-independent. DIM-C-pPhtBu decreased mitochondrial membrane potential
      (MMP) and promoted the release of cytochrome c and caspase activation and nuclear
      uptake of endonuclease G leading to apoptosis of HEC1A cells. DIM-C-pPhtBu
      specifically targeted the mitochondrial permeability transition pore complex
      (PTPC) because the DIM-C-pPhtBu-induced pro-apoptotic responses were inhibited by
      atractyloside (Atra), a compound that specifically interacts with the inner
      mitochondrial membrane adenine nucleotide transport (ANT) proteins. At the dose
      of Atra used in this study (300 microM), this compound alone did not alter the
      PTPC but inhibited the mitochondriotoxic effects of DIM-C-pPhtBu. DIM-C
      pPhtBu/DIM-C-pPhC(6)H(5) and Atra also differentially affected the ability of
      eosin-5-maleimide (EMA) to alkylate Cys160 in the ANT protein and Atra, but not
      DIM-C-pPhtBu, inhibited the exchange of ATP/ADP in isolated mitochondria
      suggesting that these pharmacophores act on different sites on the ANT protein.
      Results of this study show that the receptor-independent proapoptotic activity of
      DIM-C-pPhtBu and DIM-C-pPhC(6)H(5) were related to novel mitochondriotoxic
      activities involving inner mitochondrial ANT proteins.

PMID- 18085538
TI  - Noncovalent keystone interactions controlling biomembrane structure.
AB  - There is a biomedical need to develop molecular recognition systems that
      selectively target the interfaces of protein and lipid aggregates in
      biomembranes. This is an extremely challenging problem in supramolecular
      chemistry because the biological membrane is a complex dynamic assembly of
      multifarious molecular components with local inhomogeneity. Two simplifying
      concepts are presented as a framework for basing molecular design strategies. The
      first generalization is that association of two binding partners in a biomembrane
      will be dominated by one type of non-covalent interaction which is referred to as
      the keystone interaction. Structural mutations in membrane proteins that alter
      the strength of this keystone interaction will likely have a major effect on
      biological activity and often will be associated with disease. The second
      generalization is to view the structure of a cell membrane as three spatial
      regions, that is, the polar membrane surface, the midpolar interfacial region and
      the non-polar membrane interior. Each region has a distinct dielectric, and the
      dominating keystone interaction between binding partners will be different. At
      the highly polar membrane surface, the keystone interactions between charged
      binding partners are ion-ion and ion-dipole interactions; whereas, ion-dipole and
      ionic hydrogen bonding are very influential at the mid-polar interfacial region.
      In the non-polar membrane interior, van der Waals forces and neutral hydrogen
      bonding are the keystone interactions that often drive molecular association.
      Selected examples of lipid and transmembrane protein association systems are
      described to illustrate how the association thermodynamics and kinetics are
      dominated by these keystone noncovalent interactions.

PMID- 18085540
TI  - An investigation on the nature of the peptide at m/z 904, overexpressed in plasma
      of patients with colorectal cancer and familial adenomatous polyposis.
AB  - In an investigation devoted to the search for plasma markers for colorectal
      cancer (CRC), carried out by matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometry, a series of overexpressed peptides were identified in the
      plasma of patients. Among them the peptide with molecular weight 903 Da was the
      most abundant one, with a mean +/- (SD) relative abundance of 37 +/- 17% and a
      frequency over 60%. Interestingly, also in plasma samples of ten subjects
      affected by familial adenomatous polyposis (FAP), the peptide with molecular
      weight 903 was overexpressed. In this investigation, MALDI/MS/MS experiments were
      carried out on the ion at m/z 904 detected in the MALDI mass spectra of CRC and
      FAP patients. The data analysis by SwissProt.2007.01.09 indicates that this
      peptide is due to the sequence RPPGFSPF, found in the kininogen-1 precursor,
      which is an alpha-2-thiol proteinase inhibitor. In the case of subjects affected
      by a particular FAP syndrome, the MALDI/MS/MS spectra were quite different from
      those obtained from CRC and FAP patients. In fact, two sequences have been
      evidenced: RPPGFSPF belonging to kininogen-1 precursor, and PRKSSSSR belonging to
      Forkhead box protein 01A.

PMID- 18085539
TI  - Probing inducible nitric oxide synthase with a pterin-ruthenium(II) sensitizer
      wire.

PMID- 18085541
TI  - "Click" xylosides initiate glycosaminoglycan biosynthesis in a mammalian cell
      line.

PMID- 18085542
TI  - Rapid characterization of covalent modifications to rat brain mitochondrial
      proteins after ex vivo exposure to 4-hydroxy-2-nonenal by liquid chromatography
      tandem mass spectrometry using data-dependent and neutral loss-driven MS3
      acquisition.
AB  - The modification of mitochondrial proteins enriched from rat forebrain by the
      major lipid peroxidation product 4-hydroxy-2-nonenal (HNE) was investigated using
      high performance liquid chromatography (HPLC) and tandem mass spectrometry.
      Subcellular fractionation in conjunction with a 'shotgun-based' approach that
      involved both conventional data-dependent and neutral loss (NL)-driven MS(3) data
      acquisition on a hybrid linear ion trap-Fourier transform ion cyclotron resonance
      mass spectrometer (LTQ-FT) was utilized. Using a relatively rapid linear HPLC
      gradient (1 h) for complex mixture analysis, 24 sites of HNE modification on 15
      unique proteins were identified which corresponded exclusively to Michael adduct
      formation on histidine residues. Since a number of HNE-modified peptides produced
      a predominant HNE NL fragment-ion signal upon collision-induced dissociation
      (CID), NL-driven MS(3) data-dependent acquisition was a valuable method to
      enhance fragmentation information for these particular modified peptides. Of the
      24 HNE modification sites identified, approximately 25% were determined from the
      MS(3) spectra alone. We envision the reported methodology as an efficient
      screening approach for HNE modification site selectivity that could ultimately
      provide a foundation for the development of targeted schemes for the
      characterization of in vivo HNE-protein adducts.

PMID- 18085543
TI  - Genetic selection of cyclic peptide Dam methyltransferase inhibitors.

PMID- 18085545
TI  - AP/MALDI-MS complete characterization of the proteolytic fragments produced by
      the interaction of insulin degrading enzyme with bovine insulin.
AB  - The prominent role that insulin degrading enzyme (IDE) has in the clearance of
      insulin as well as of other molecules such as amyloid-beta has recently drawn
      much interest in the scientific community toward this protease. In order to give
      an insight into the manner of interaction of IDE with its substrates, several
      papers have focused on the structure of the IDE/insulin complex. In this
      scenario, although the cleavage sites involved in the interaction of insulin with
      IDE are known, a convenient experimental method that is able to identify in a
      complete and unambiguous way, all the peptide fragments generated by such
      interaction has yet to be found. MS-based experiments have often represented to
      be invaluable tools for the assessment of the cleavage sites, but the reported MS
      spectra always show a partial coverage of all the peptide fragments generated by
      the enzyme interaction, lacking a complete characterization. In this work, we
      report a new experimental procedure by which an unambiguous as well as complete
      assignment of all the peptide fragments generated by the interaction of insulin
      with IDE is described. Atmospheric pressure/matrix-assisted laser desorption
      ionization (AP/MALDI) mass spectra are reported and the data recorded, together
      with the introduction of a reduction/alkylation step, allows us to fully
      characterize the cleavage sites of the bovine insulin interacting with IDE.
      Different experimental conditions are screened and some insights into the
      IDE/insulin system regarding preference of the cleavage and its dependence on
      particular experimental conditions used are also given. Investigation on the
      tendency that different insulin fragments have toward aggregation is also carried
      out. Good reproducibility, global and unambiguous assignment, low time-consuming
      experimental procedure, and requirements of enzyme in small amounts are some of
      the advantages of the proposed AP/MALDI based approach.

PMID- 18085544
TI  - Regulating enzymatic activity with a photoswitchable affinity label.

PMID- 18085546
TI  - No association between prostate apoptosis response 4 gene (PAWR) in schizophrenia
      and mood disorders in a Japanese population.
AB  - Altered dopamine D2 receptor (D2R) is hypothesized to be a susceptibility factor
      for major psychosis. Recent studies showed that a new intracellular protein,
      prostate apoptosis response 4 (Par-4), plays a critical role in D2R signaling. We
      conducted a genetic association analysis between Par-4 gene (PAWR) and
      schizophrenia and mood disorders in a Japanese population (schizophrenia: 556
      cases, bipolar disorder (BP): 150 cases, major depressive disorder (MDD): 312
      cases and 466 controls). Applying the recommended 'gene-based' association
      analysis, we selected five tagging SNPs in PAWR from the HapMap database. No
      significant association was obtained found with schizophrenia or MDD or BP. We
      found a significant association of one tagging SNP with BP in a genotype-wise
      analysis (P = 0.0396); however, this might be resulted from type I error due to
      multiple testing (P = 0.158 after SNPSpD correction). Considering the size of our
      sample and strategy, our results suggest that the PAWR does not play a major role
      in schizophrenia or mood disorders in the Japanese population.

PMID- 18085547
TI  - Mass spectrometry-based survey of age-associated protein carbonylation in rat
      brain mitochondria.
AB  - There is a body of evidence lending credence to the idea that oxidative stress
      may be responsible for age-related deleterious changes in brain function, and
      that protein carbonylation is a potential marker for such changes. An
      investigation of oxidative damage to mitochondrial proteins from aged rat brains
      was done using gel electrophoresis coupled with carbonylation-specific
      immunostaining. Six proteins that appeared to be susceptible to oxidative
      modification were identified by in-gel trypsin digestion followed by matrix
      assisted laser desorption/ionization mass spectrometry and tandem mass
      spectrometry. Two subunits of the H(+)-transporting ATP synthase, adenine
      nucleotide translocator, voltage-dependent anion channel, glutamate oxaloacetate
      transaminase, and aconitase were identified as likely targets of age-associated
      carbonylation.

PMID- 18085548
TI  - De novo sequencing of a 21-kDa cytochrome c4 from Thiocapsa roseopersicina by
      nanoelectrospray ionization ion-trap and Fourier-transform ion-cyclotron
      resonance mass spectrometry.
AB  - We have determined the primary structure of cytochrome c(4) from Thiocapsa
      roseopersicina by de novo protein sequencing using the 'bottom up' approach.
      Three different enzymes (trypsin, endoproteinase Lys-C, and endoproteinase Glu-C)
      were employed to prepare four different sets of proteolytic digests. The
      digestion strategy was designed to permit a gradual buildup of smaller peptides
      into larger ones that were overlapped to yield the complete protein sequence. In
      this way we countered the main problem: peptides larger than about 1500 Da were
      difficult to sequence fully by tandem mass spectrometry. Direct infusion and
      online liquid chromatography were used on a linear ion trap Fourier-transform ion
      cyclotron resonance hybrid instrument. The high resolving power, high mass
      accuracy and the availability of electron capture dissociation and collision
      induced dissociation were essential to achieve full sequence coverage. The
      software DeNovoX complemented by manual interpretation was used to generate
      sequence information from tandem mass spectra. The predominantly automated nature
      of data acquisition and handling allowed for a relatively straightforward and
      fast procedure, which could compete with the mainstream alternative of nucleotide
      sequence determination.

PMID- 18085549
TI  - Claisen rearrangement induced by low-energy collision of ESI-generated,
      protonated benzyloxy indoles.
AB  - The Claisen rearrangement is a well-known process occurring in condensed phase.
      In the gas-phase protonated allyl phenyl ethers, propargyl phenyl ethers, and N
      allyl aniline produced by positive ion chemical ionization undergo Claisen
      rearrangement. This reaction has been observed even in the case of odd-electron
      molecular ions. Phenyl allenyl ether molecular ions actually undergo Claisen
      rearrangement, producing intense [M - CO](+*) ions. In this investigation, the
      behavior of protonated benzyloxy indole and some of its derivatives, obtained in
      electrospray conditions, is described. Low-energy MS/MS experiments carried out
      on [M + H](+) species show CO loss and an unexpected water loss: both can be
      justified only by the occurrence of Claisen rearrangement. Deuterium labeling
      experiments confirm this mechanism. The influence of different substituents in
      the indole moiety is discussed.

PMID- 18085550
TI  - Mass spectrometric study of selected precursors and degradation products of
      chemical warfare agents.
AB  - Selected precursors and degradation products of chemical warfare agents namely
      N,N-dialkylaminoethane-2-ols, N,N-dialkylaminoethyl-2-chlorides and some of
      related N-quaternary salts were studied by means of electrospray ionization
      multiple tandem mass spectrometry (ESI-MS(n)). Proposed structures were confirmed
      with accurate mass measurement. General fragmentation patterns of these compounds
      are discussed in detail and suggested processes are confirmed using deuterated
      standards. The typical processes are elimination of alkene, hydrogen chloride, or
      water, respectively. Besides, elimination of ethene from propyl chain under
      specific conditions was observed and unambiguously confirmed using exact mass
      measurement and labelled standard. The potential of mass spectrometry to
      distinguish the positional isomers occurring among the studied compounds is
      reviewed in detail using two different MS instruments (i.e. ion trap and hybrid
      quadrupole-time of flight (Q-TOF) analyzer). A new microcolumn liquid
      chromatography (microLC)/MS(n) method was designed for the cases where the
      resolution based solely on differences in fragmentation is not sufficient. Low
      retention of the derivatives on reversed phase (RP) was overcome by using
      addition of less typical ion pairing agent (1 mM/l, 3,5-dinitrobenzoic acid) to
      the mobile phase (mixture water : acetonitrile).

PMID- 18085551
TI  - Haplotype analysis of the IGF2-INS-TH gene cluster in Parkinson's disease.
AB  - Idiopathic Parkinson's disease is a common movement disorder characterized by a
      loss of dopaminergic neurons in the substantia nigra. Its pathogenesis is
      postulated to involve complex interactions between genetic susceptibility and
      environmental exposures. The IGF2-INS-TH gene cluster on the telomeric end of
      human chromosome 11 is a gene rich region expressing several proteins important
      for dopamine neuron homeostasis. We used a haplotyping approach to determine
      whether common genetic variation in the IGF2-INS-TH cluster influences the risk
      of idiopathic Parkinson's disease in a Caucasian case-control group recruited
      from Brisbane, Australia. Three tagging polymorphisms, the SNPs, rs680 and rs689
      and the microsatellite, HUMTH01, were genotyped in 215 cases and 215 age- and
      gender-matched controls. Eight common haplotypes accounted for 91% of the genetic
      variation in our control group and one haplotype, IGF2-INS-TH*6, was
      significantly under-represented among the cases with idiopathic Parkinson's
      disease (OR = 0.42, 95% CI = 0.25-0.72, P-value = 0.001). Analysis of the
      individual polymorphisms showed that the IGF2-rs680 alternate 'A' allele
      accounted for the majority of the protective effect. Our findings suggest that
      common genetic variants in the IGF2-INS-TH cluster modify susceptibility to
      idiopathic Parkinson's disease.

PMID- 18085552
TI  - A biological window on psychological development.
AB  - The articles in this special issue of Developmental Psychobiology were presented
      in May 2005 at an international institute on developmental science hosted by the
      University of North Carolina at Chapel Hill. Conducted annually at one of the
      participating universities, these meetings are intended to foster collaboration
      and build consensus on specific theoretical, methodological, and analytical
      issues faced by developmentally oriented researchers. The overall goal of the
      2005 meeting, titled "Integrating Biology and Developmental Science," was to
      identify different ways by which a developmental study of psychological phenomena
      in their joint biological and behavioral aspects may shed new light on their
      organization in the individual. The six contributions to this special issue
      illustrate how a biological window on developmental processes can further this
      scientific endeavor.

PMID- 18085553
TI  - Using the proper vocabulary.
AB  - This paper makes three points. First, inferences from biological and
      psychological evidence pertaining to psychological constructs must use distinct
      vocabularies because they represent different phases of a cascade of processes.
      Second, there are necessarily indeterminate relations between phases of the
      cascade that begins with an incentive evoking a brain state which, in turn, may
      generate a psychological reaction and/or action. Finally, all biological and
      psychological phenomena occur in particular species and specific contexts; hence
      it is useful to append to every conclusion information on the agent and the
      setting in which the evidence was gathered.

PMID- 18085555
TI  - Toward a neuro-developmental account of the development of declarative memory.
AB  - The study of the biological bases of memory has a long history. Based on research
      with patients with specific lesions and disease, animal models, and neuroimaging
      studies, the neural substrate that supports declarative memory in adults has been
      relatively well articulated. By contrast, studies of the neural bases of memory
      in development is in its infancy. Yet joint consideration of the processes
      involved in building a memory trace, and of the time course of development of the
      neural structures involved, has contributed to the generation of specific
      predictions regarding the sources of age-related change. Specifically, there are
      suggestions that in infancy and very early childhood, encoding and consolidation
      processes account for substantial age-related variance in long-term declarative
      memory. With development, the locus of age-related variability in the
      vulnerability of memory traces shifts to the later-stage processes of memory
      storage and retrieval. These insights are afforded by consideration of multiple
      levels of analysis, from the biological to the behavioral.

PMID- 18085554
TI  - Inhibitory deficits in Tourette's syndrome.
AB  - A developmental approach to the study of psychopathology can broaden
      understanding of a wide variety of complex psychological disorders. This article
      reviews research on Tourette's syndrome (TS), a developmental disorder
      characterized by unwanted motor and vocal tics. Over the past decade, knowledge
      of the neurobiology and pathophysiology of TS has progressed rapidly. The
      application of brain imaging techniques, primarily magnetic resonance imaging, to
      the study of Tourette's has increased knowledge of structural and functional
      deficits in brain areas associated with behavioral and psychological disturbances
      in the disorder. By reviewing some of this work, we will describe one way in
      which knowledge of brain function in TS has both informed and been informed by a
      developmental science approach. In particular, we will consider the extent to
      which the cognitive and emotional development of persons with TS may be affected
      by specific neurobiological characteristics of the disorder.

PMID- 18085556
TI  - Exploratory behavior in mice selectively bred for developmental differences in
      aggressive behavior.
AB  - The development and expression of exploratory behavior was assessed in the Cairns
      lines of Institute for Cancer Research (ICR) mice that were selectively bred for
      differences in aggressive behavior, with a high-aggressive 900 line, low
      aggressive 100 line, and control 500 line. Four paradigms were employed.
      Developmental changes were evident in the complex novel arena, with older males
      faster to contact a novel object, and ambulating more than young males. Within
      the control 500 line, older males showed longer latency to emerge from the home
      cage, and shorter latency to contact novel objects. In the 900 line, younger
      males showed this same pattern. R. B. Cairns proposed that line differences in
      aggressive behavior arise through alterations in developmental timing [Cairns et
      al. [1983] Life-span developmental psychology (Vol. 5). New York: Academic Press;
      Gariepy et al. [2001] Animal Behaviour 61: 933-947]. The early appearance of
      mature patterns of exploratory behavior in 900 line males supports this
      interpretation. The 900 line males also appear to be behaviorally inhibited in
      novel settings such as the light-dark box and the neohypophagia paradigm,
      compared to the 500 and 100 lines (Experiments 1, 2, and 4). Moreover, in the
      most complex apparatus, the novel arena, 900 line males were slowest to exit the
      home cage, and fastest to contact a novel object. The apparent contrast in these
      parameters of exploratory behavior is discussed in relation to T. C. Schneirla's
      [1965 Advances in the study of behavior (Vol. 1). New York: PN Academic] approach
      withdrawal theory.

PMID- 18085557
TI  - Gene environment interplay: nonhuman primate models in the study of resilience
      and vulnerability.
AB  - Identifying how individual differences in risk for disease emerge is a major
      target for biomedical research. In many cases, however, the most lightly
      traversed avenues of this type of basic and clinical research are those that
      begin with a focus on early development. It appears likely that early influences
      may be pivotal in lifetime risk of disease and other adverse outcomes.
      Nonetheless, understanding the constellation of interacting biological,
      experiential, social factors that influence this risk has proved a relatively
      elusive target. Better specification of routes of interplay between these
      factors, as well as definitions of the mechanisms by which they affect change,
      are essential goals for numerous research areas. Furthermore, progress towards
      these goals is unlikely without meaningful integration of diverse disciplines,
      among them biology and developmental science.

PMID- 18085558
TI  - On the implications of the classical ergodic theorems: analysis of developmental
      processes has to focus on intra-individual variation.
AB  - It is argued that general mathematical-statistical theorems imply that standard
      statistical analysis techniques of inter-individual variation are invalid to
      investigate developmental processes. Developmental processes have to be analyzed
      at the level of individual subjects, using time series data characterizing the
      patterns of intra-individual variation. It is shown that standard statistical
      techniques based on the analysis of inter-individual variation appear to be
      insensitive to the presence of arbitrary large degrees of inter-individual
      heterogeneity in the population. An important class of nonlinear epigenetic
      models of neural growth is described which can explain the occurrence of such
      heterogeneity in brain structures and behavior. Links with models of
      developmental instability are discussed. A simulation study based on a chaotic
      growth model illustrates the invalidity of standard analysis of inter-individual
      variation, whereas time series analysis of intra-individual variation is able to
      recover the true state of affairs.

PMID- 18085559
TI  - Development of inter-manual transfer of shape information in infancy.
AB  - Inter-manual transfer of shape information was studied with
      habituation/dishabituation procedures in 2- and 6-month-old infants. Both age
      groups habituated to a shape repeatedly placed in one hand and dishabituated when
      a new shape was placed in the same hand. Subsequent testing revealed that only
      the 2-month olds dishabituated when the habituated shape was placed in the
      opposite hand and that only the 6-month olds dishabituated when a new shape was
      placed in the opposite hand. These results indicate that inter-manual transfer of
      hand information occurs by 2-months of age and that inter-manual transfer of
      shape information emerges between 2 and 6 months of age. The implications of the
      findings are discussed.

PMID- 18085560
TI  - Body sway and sensory motor coupling adaptation in children: effects of distance
      manipulation.
AB  - The purpose of this investigation was to examine coupling between visual
      information and body sway in children and young adults at various distances from
      a moving room front wall. Sixty children (from 4 to 14 years old) and 10 young
      adults stood upright inside a moving room that was oscillated at .2 and .5 Hz, at
      distances of .25, .5, 1, and 1.5 m from a front wall. Visual information induced
      body sway in all participants in all conditions. Young children swayed more than
      older participants, whether the moving room was oscillated or not. Coupling
      between visual information and body sway became stronger and the room movement
      influence became weaker with age. Up to the age of 10, coupling strength between
      visual information and body sway and the room movement influence were distance
      dependent. Postural control development appears to be dependent on how children
      reweight the contribution of varying sensory cues available in environment in
      order to control body sway.

PMID- 18085561
TI  - The effect of experience on the development of tactual-visual transfer in
      pigtailed macaque monkeys.
AB  - The study described here is the first to experimentally demonstrate the effects
      of experience on the development of tactual-visual transfer. Infant pigtailed
      macaque monkeys (Macaca nemestrina) were reared from birth to 2 months of age in
      special cages that allowed the separation of tactual and visual experience. When
      assessed on a battery of measures at the end of the 2-month period, animals
      reared without the opportunity to integrate information across the two sensory
      modalities performed at chance levels on a paired-comparison measure of tactual
      visual transfer and performed worse than controls in a visually guided reaching
      task. After living in the standard laboratory environment for 2 additional
      months, they were reassessed. While their visually guided reaching now no longer
      differed from that of controls, they continued to perform at chance on the
      tactual-visual transfer assessment and their performance on this task was
      significantly worse than the control groups. Performance on visual acuity and
      visual recognition memory measures did not differ between groups at either age,
      suggesting that the deficit was limited to tactual-visual functioning. The
      results are discussed in terms of a possible sensitive period during which
      specific environmental input is required for the development of normal tactual
      visual cross-modal processing.

PMID- 18085562
TI  - Developmental differences in infants' use of an object's shape to grasp it
      securely.
AB  - This study examined twenty two 11- and 13-month-old infants' approach and grasp
      of two objects-one symmetric and one asymmetric-in an effort to understand
      infants' use of shape information to plan motor action. At first contact, all
      infants grasped the asymmetrical object further from its center of mass than the
      symmetrical object. In addition, results highlighted developmental differences in
      infants' abilities to correct for less stable hand placements, to maintain
      control of the objects without dropping, strategies used to obtain the objects,
      and latencies to grasp the objects. Older infants showed more effective skills in
      each of the aforementioned areas. Implications for our understanding of the
      development of processing of visual information for action are discussed.

PMID- 18085563
TI  - BCL-2 counteracts Doppel-induced apoptosis of prion-protein-deficient Purkinje
      cells in the Ngsk Prnp(0/0) mouse.
AB  - The pro-apoptotic factor BAX has recently been shown to contribute to Purkinje
      cell (PC) apoptosis induced by the neurotoxic prion-like protein Doppel (Dpl) in
      the prion-protein-deficient Ngsk Prnp(0/0) (NP(0/0)) mouse. In view of cellular
      prion protein (PrP(c)) ability to counteract Dpl neurotoxicity and favor neuronal
      survival like BCL-2, we investigated the effects of the anti-apoptotic factor BCL
      2 on Dpl neurotoxicity by studying the progression of PC death in aging NP(0/0)
      Hu-bcl-2 double mutant mice overexpressing human BCL-2 (Hu-bcl-2). Quantitative
      analysis showed that significantly more PCs survived in NP(0/0)-Hu-bcl-2 double
      mutants compared with the NP(0/0) mutants. However, number of PCs remained
      inferior to wild-type levels and to the increased number of PCs observed in Hu
      bcl-2 mutants. In the NP(0/0) mutants, Dpl-induced PC death occurred
      preferentially in the aldolase C-negative parasagittal compartments of the
      cerebellar cortex. Activation of glial cells exclusively in these compartments,
      which was abolished by the expression of Hu-bcl-2 in the double mutants,
      suggested that chronic inflammation is an indirect consequence of Dpl-induced PC
      death. This partial rescue of NP(0/0) PCs by Hu-bcl-2 expression was similar to
      that observed in NP(0/0):Bax(-/-) double mutants with bax deletion. Taken
      together, these data strongly support the involvement of BCL-2 family-dependent
      apoptotic pathways in Dpl neurotoxicity. The capacity of BCL-2 to compensate
      PrP(c) deficiency by rescuing PCs from Dpl-induced death suggests that the BCL-2
      like property of PrP(c) may impair Dpl-like neurotoxic pathways in wild-type
      neurons.

PMID- 18085564
TI  - Cross-midline interactions between mouse commissural hindbrain axons contribute
      to their efficient decussation.
AB  - Information from both sides of the brain is integrated by axons that project
      across the midline of the central nervous system via numerous commissures present
      at all axial levels. Despite the accumulated experimental evidence, questions
      remain regarding the formation of commissures in the presence of strong repulsive
      signals in the ventral midline. Studies from invertebrates suggest that
      interaction at the midline between homologous axons of specific decussating
      neurons contributes to efficient midline crossing, but such evidence is lacking
      in vertebrate systems. We performed experiments to determine whether commissural
      axons of the caudal region of the hindbrain interact with their contralateral
      counterparts at the ventral midline and to evaluate the relevance of this
      reciprocal interaction. Double anterograde axon labeling with lipophilic tracers
      revealed close apposition between growth cones of contralateral pioneer
      decussating axons at the midline. Later, we detected fasciculation between
      contralateral axons that is maintained even after they have crossed the midline.
      Blocking axon projections unilaterally with a solid mechanical barrier decreased
      dramatically the midline crossing of the equivalent population from the
      contralateral side. Decussation was also blocked by a unilateral barrier
      permeable to diffusible molecules but not by an axon-permeable barrier. These
      results suggest that in the caudal region of the hindbrain, midline crossing is
      facilitated by interactions between decussating contralateral axon partners.

PMID- 18085565
TI  - Ganglion ultrastructure in phylactolaemate Bryozoa: evidence for a
      neuroepithelium.
AB  - In contrast to other Bryozoa, members of the subtaxon Phylactolaemata bear a
      subepithelial cerebral ganglion that resembles a hollow vesicle rather than being
      compact. In older studies this ganglion was said to originate by an invagination
      of the pharyngeal epithelium. Unfortunately, documentation for this is
      fragmentary. In chordates the central nervous system also arises by an
      invagination-like process, but this mode is uncommon among invertebrate phyla. As
      a first attempt to gather more data about this phenomenon, cerebral ganglia in
      two phylactolaemate species, Fredericella sultana and Plumatella emarginata, were
      examined at the ultrastructural level. In both species the ganglion bears a small
      central lumen. The ganglionic cells are organized in the form of a
      neuroepithelium. They are polarized and interconnected by adherens junctions on
      their apical sides and reside on a basal lamina. The nerve cell somata are
      directed towards the central lumen, whereas the majority of nervous processes are
      distributed basally. Orientation of the neuroepithelial cells can be best
      explained by the possibility that they develop by invagination. A comparison with
      potential outgroups reveals that a neuroepithelial ganglion is at least derived.
      Since, however, a reliable phylogenetic system of the Bryozoa is missing, a
      decision on whether such a ganglion is apomorphic for Bryozoa or evolved within
      this taxon can hardly be made.

PMID- 18085566
TI  - Pharmacogenetic study of atypical antipsychotic drug response: involvement of the
      norepinephrine transporter gene.
AB  - The identification of genetic factors underlying individual differences in
      antipsychotic drug response is of major interest. We investigated the involvement
      of two norepinephrine transporter gene polymorphisms in response to
      antipsychotics, comparing patients with strong and weak response to olanzapine
      and risperidone. We prospectively assessed short-term drug response in 75
      Caucasian schizophrenic patients treated with these drugs, using the Positive and
      Negative Syndrome Scale. We then assessed the association between two SLC6A2 gene
      polymorphisms and drug response in this sample. No significant difference in
      genotype distribution was found between responders and non-responders, for the
      G1287A or T-182C polymorphism. The improvement in PANSS positive subscore was
      significantly greater in patients homozygous for the A1287 allele than in other
      patients, and significantly smaller in patients homozygous for the C-182 allele
      than in other patients. Our results suggest that these polymorphisms are
      specifically involved in the variation of positive symptoms in schizophrenic
      patients.

PMID- 18085567
TI  - Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation.
AB  - XX true hermaphroditism, also know as ovotesticular disorder of sexual
      development (DSD), is a disorder of gonadal development characterized by the
      presence of both ovarian and testicular tissue in a 46,XX individual. The genetic
      basis for XX true hermaphroditism and sex reversal syndromes unrelated to SRY
      translocation is still mostly unclear. We report mutational analysis of the RSPO1
      gene in a 46,XX woman with true hermaphroditism, palmoplantar keratoderma,
      congenital bilateral corneal opacities, onychodystrophy, and hearing impairment.
      R-spondin1 is a member of the R-spondin protein family and its pivotal role in
      sex determination has been recently described. We identified a homozygous splice
      donor-site mutation in the RSPO1 gene in our patient. We found that the
      c.286+1G>A mutation led to an aberrantly spliced mRNA (r.95_286del), which is
      presumably translated into a partially functional protein (p.Ile32_Ile95del). Our
      case demonstrates for the first time, to our knowledge, that XX true
      hermaphroditism can be caused by a single gene mutation. The reported findings
      represent a further step toward a complete understanding of the complex
      mechanisms leading to DSDs.

PMID- 18085569
TI  - Charge state effect on the zwitterion influence on stability of non-covalent
      interaction of single-stranded DNA with peptides.
AB  - Negative ion ESI mass spectrometry was used to study the gas-phase stability and
      dissociation pathways of peptide-DNA complexes. We show that bradykinin and three
      modified peptides containing the basic residue arginine or lysine form stable
      interactions with single-stranded oligonucleotides. ESI-MS/MS of complexes of
      T(8) with PPGFSPFRR resulted in a major dissociation pathway through cleavage of
      the peptide covalent bond. The stability of the complex is due to electrostatic
      interaction between the negatively charged phosphate group and the basic side
      chain of the arginine and lysine residues as demonstrated by Vertes et al. and
      Woods et al. In fact, the present work establishes the role played by zwitterions
      on complex stabilisation. The presence of protons in nucleobase and/or amino acid
      contributes in reinforcing the strength of the salt bridge (SB) interaction. The
      zwitterionic form of the most basic of amino acid residues, arginine, is assumed
      to form a strong SB interaction to the negatively charged phosphate groups of
      DNA. This non-covalent complex is stable enough to withstand disruption of the
      non-covalent interaction and to first break the covalent bond. Moreover, the
      dependence of fragmentation patterns upon the complex charge state is explained
      by the fact that the net number of negative charges modulates the number of
      zwitterionic sites, which stabilise the complexes. Finally, the weak influence of
      the nucleobase is assumed by the existence of competition for proton addition
      between the nucleobase and the R/K side chain leading to a decrease in the
      stabilisation of the SB interaction.

PMID- 18085570
TI  - Correlation between energetics of collisionally activated decompositions,
      interaction energy and biological potency of carbamate FAAH inhibitors.

PMID- 18085571
TI  - The study of isotopic fractionation in the process of analysis of isotopic ratios
      15N/14N and 18O/16O in nitrate from water.

PMID- 18085572
TI  - Mass spectrometry analysis of gliadins in celiac disease.
AB  - In recent years, scientific research on wheat gluten proteins has followed three
      main directions aimed at (1) finding relationships between individual genetic
      alleles coding for gliadins, high or low molecular weight glutenin subunits, and
      the viscoelastic dough properties of flour-derived products such as pasta and
      bread; (2) identifying prolamins and derived peptides involved in celiac disease,
      a pathological condition in which the small intestine of genetically predisposed
      individuals is reversibly damaged; and (3) developing and validating sensitive
      and specific methods for detecting trace amounts of gluten proteins in gluten
      free foods for celiac disease patients. In this review, the main aspects of
      current and perspective applications of mass spectrometry and proteomic
      technologies to the structural characterization of gliadins are presented, with
      focus on issues related to detection, identification, and quantification of
      intact gliadins, as well as gliadin-derived peptides relevant to the biochemical,
      immunological, and toxicological aspects of celiac disease.

PMID- 18085574
TI  - Consolidative involved field radiotherapy after high dose chemotherapy and
      autologous stem cell transplantation for non-Hodgkin's lymphoma: a case-control
      study.
AB  - The role of involved field radiation therapy (IF-RT) after high dose chemotherapy
      (HDC) with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma
      (NHL) has not been conclusively defined. It has been hypothesized that HDC might
      obviate the need of consolidative IF-RT. A retrospective matched-pair analysis of
      patients undergoing HDC and ASCT with or without consolidative IF-RT has been
      performed. Fifteen patients treated with IF-RT after ASCT were compared with 15
      patients without IF-RT, identical for histology, stage and treatment response to
      HDC/ASCT as well as comparable for international prognostic index (IPI) score,
      age and gender. After a mean follow-up time of 65 +/- 45 months, none of the
      patients with consolidative IF-RT following HDC and ASCT relapsed within the
      involved field compared to six patients without consolidative IF-RT (IF-failure
      risk at 5 years: 0% vs. 40%; p < 0.005). In most of the cases, local relapse was
      seen in patients with bulky disease. The 5-year risk for loco-regional failure
      was 7% after consolidative IF-RT and 38% in patients without IF-RT (p = 0.02)
      while the 5-year risk for developing distant recurrences was similar in both
      groups (30% with IF-RT vs. 35% non-IF-RT; p = 0.7). Overall survival at 5 years
      was similar with 79% (IF-RT) and 65% (non-IF-RT), respectively (p = 0.2). Acute
      toxicity due to consolidative IF-RT was mild in most cases and severe acute
      toxicity was noticed in only one patient (7%). Long-term toxicities observed
      after IF-RT were coronary artery disease, secondary malignancy unrelated to the
      RT-field, angina abdominalis, hypothyroidism and teeth decay. Recurrence of NHL
      at sites of macroscopic disease remains common despite HDC. IF-RT achieves
      excellent local regional control and consolidative IF-RT after ASCT seems
      indicated, particularly in patients with bulky disease. In the absence of a
      prospective randomized trial and proven impact on survival rates, IF-RT can be
      recommended as an option post-ASCT to enhance local disease control.

PMID- 18085576
TI  - Perspectives on disparities in depression care.
AB  - Depression is a major public health problem and a leading cause of disability
      worldwide. Compounding the high rates of morbidity and mortality and treatment
      challenges associated with depression are the tremendous disparities in quality
      of mental health care that exist between the majority of the population and those
      of racial and ethnic minorities. Although more study data are available on
      depression care for African Americans than for other groups, racial and ethnic
      minorities overall are less likely than whites to receive an accurate diagnosis,
      to receive care according to evidence-based guidelines, and to receive an
      antidepressant upon diagnosis. Multiple factors contribute to these disparities,
      among them socioeconomic and cultural issues and prejudices among patients and
      health care providers. Closing the gap that exists between what depression care
      is and what depression care could be begins with clinicians' recognizing the
      relevance of culture to care. Opportunities exist within the broader context of
      medical education, including continuing medical education (CME), to prepare
      health care professionals to address the myriad issues related to managing
      depression.

PMID- 18085577
TI  - How quality improvement interventions can address disparities in depression.
AB  - The quality of depression care, especially care received by minorities, needs
      improvement. Several interventions have been developed for the purpose of
      improving the quality of depression management in primary care, including quality
      improvement strategies employing disease management approaches, the chronic care
      model, and the Breakthrough Collaborative Series developed by the Institute for
      Healthcare Improvement. This article reviews these interventions and examines
      their potential to contribute to the improvement of depression care.

PMID- 18085578
TI  - A conceptual model for using action inquiry technologies to address disparities
      in depression.
AB  - Disparities in depression care remain an important problem in the United States.
      Action inquiry technologies may assist individuals and communities in their
      attempts to reduce or eliminate these disparities--and the multiple factors
      contributing to them--through a recurring cycle of planning, action, evaluation,
      and new actions based on reflections about what occurred during previous actions.
      This article will briefly review different action inquiry methods--specifically,
      participatory action research (PAR) in communities and action research in
      physicians' practices and offices of continuing medical education (CME). The
      authors develop a conceptual model in which those involved in providing,
      receiving, and improving depression care can use action inquiry strategies that
      are coordinated using the domains-based outcomes assessment model. This
      conceptual model may help CME planners collaborate with others to address
      disparities in depression care.

PMID- 18085579
TI  - Collaboration to improve depression care for ethnic and racial minorities.

PMID- 18085580
TI  - Addressing disparities in diagnosing and treating depression: a promising role
      for continuing medical education.
AB  - Depression is a very common reason that individuals seek treatment in the primary
      care setting. However, advances in depression management are often not integrated
      into care for ethnic and racial minorities. This supplement summarizes evidence
      in six key areas--current practices in diagnosis and treatment, disparities,
      treatment in managed care settings, quality improvement, physician learning, and
      community-based participatory research--used to develop an intervention concept
      described in the concluding article. Evidence of gaps in the care for minorities,
      while discouraging, presents unique opportunities for medical educators to
      develop interventions with the potential to change physician behavior and thereby
      reduce disparities and enhance patient outcomes.

PMID- 18085581
TI  - Current practices in depression care.
AB  - Despite improved awareness among the medical community concerning common mental
      health disorders, the high prevalence of depression in the United States remains
      unchanged and has been compounded by increasing evidence of gaps in mental health
      care for ethnic and racial minorities. Thus, there is a strong need for the
      timely creation of comprehensive educational initiatives aimed at improving the
      quality of care provided by mental health professionals and primary care
      physicians. Fundamental to this process is the examination of current treatment
      standards, as well as identification of practices that require improved physician
      education. Consistent use of appropriate screening tools, diagnostic accuracy and
      timeliness, continual assessment of illness severity, adherence to practice
      guidelines, and individualized patient care need heightened attention to improve
      outcomes. This article describes the most prevalent types of depression and
      summarizes current practices in depression care, with an emphasis on treatment
      standards and opportunities for improved performance.

PMID- 18085582
TI  - Disparities in depression care in managed care settings.
AB  - The implementation of managed health care two decades ago produced sweeping
      changes in the delivery of health care. A large number of patients who have
      depression are cared for in managed care settings. Despite the fact that managed
      health care programs have offered the advantage of affordable and effective
      treatment of depression to many patients, racial and ethnic minorities remain
      underdiagnosed and undertreated. Diagnosis of depression, prescribing of
      antidepressant therapy, and referral for psychotherapy occur significantly less
      often in minority patients compared with whites. In the managed care setting, a
      number of issues at the physician level may negatively affect the quality of
      depression care, including attitudes toward psychiatry and mental health
      services, unfamiliarity with best practice guidelines for depression, and lack of
      cultural competency. On the other hand, a number of innovative approaches (eg,
      collaborative care) have demonstrated effectiveness in managed care settings. In
      some cases, physician education can be integrated with these approaches to assist
      health care providers in managed care organizations to provide the best possible
      depression care. This article focuses on issues relevant to depression care of
      minorities in the managed care sector, cites strategies for improving quality of
      depression care, and discusses implications for CME.

PMID- 18085583
TI  - A conceptual model of CME to address disparities in depression care.
AB  - The gap between best practices and actual practice in depression care--the
      difference between "what should be" and "what is"--is wider for ethnic and racial
      minorities than for the general population. Education alone is not reducing the
      gap or improving outcomes. Interventions such as the chronic care model have
      demonstrated improvements in physician performance and patient health status,
      both in the general population and among ethnic and racial minorities. Recent
      reviews of continuing medical education (CME) have shown that it is effective
      when the planned activities include (1) needs assessment and a focus on higher
      level outcomes, (2) multiple ongoing activities that are sequenced for learning,
      (3) planning that considers the context in which the learned principles will be
      applied, (4) interactivity, and (5) active learning. The authors describe an
      approach to planning CME reflecting these five factors and suggest that CME
      planned in this way be combined with the chronic care model to enhance outcomes
      further.

PMID- 18085584
TI  - Improving depression care for ethnic and racial minorities: a concept for an
      intervention that integrates CME planning with improvement strategies.
AB  - Depression is one of the most common reasons that individuals seek treatment in
      the primary care setting. Research in the past 15 years has shown that dramatic
      improvement in the management of patients with depression is possible. Advances
      in pharmacotherapy and delivery of depression care have been reported, but few
      currently benefit members of ethnic and racial minorities. Educating physicians
      and other health professionals has been suggested as one approach to address the
      issues related to disparities in depression care. There is little evidence,
      however, that education alone is effective. The authors of this article believe
      that incorporating physician learning activities that are planned using
      approaches that have been shown to be effective in interventions currently
      demonstrating some success in improving depression care provided to ethnic and
      racial minorities will enhance the impact and sustainability of these
      interventions. This article--the conclusion of this supplement--will describe an
      intervention concept that integrates a quality improvement model (the Institute
      for Health Improvement's Breakthrough Series Collaborative model) with an
      evidence-based approach to planning CME and supports the integration by using
      action inquiry technologies and community-based participatory research methods.
      Relevant approaches from implementation research are discussed, and suggestions
      for testing the intervention concept are provided.

PMID- 18085586
TI  - PI3K signaling effects in hypothalamic neurons mediated by estrogen.
AB  - Multiple mechanisms mediate the effects of estrogen in the central nervous
      system, including signal transduction pathways such as protein kinase A, protein
      kinase C, and phosphatidylinositol 3-kinase (PI3K) pathways. Previously we
      demonstrated that estrogen regulates a number of PI3K-related genes in the
      hypothalamus, including the PI3K p55gamma regulatory subunit. We hypothesized
      that PI3K activation is critical for the effects of estrogen and that the
      p55gamma subunit may be more prevalent than the p85alpha regulatory subunit in
      the hypothalamus. Therefore, in the present study, we compared the mRNA
      distribution of the p55gamma and p85alpha regulatory subunits by using in situ
      hybridization in guinea pig. Expression level of p55gamma mRNA was greater than
      p85alpha in most hypothalamic nuclei. Twenty-four hours of estrogen treatment
      increased p55gamma mRNA expression in the paraventricular, suprachiasmatic,
      arcuate, and ventromedial nuclei, and little or no change was observed for
      p85alpha mRNA. Quantitative real-time PCR confirmed the in situ hybridization
      results. Next, we investigated the general role of PI3K signaling in the estrogen
      mediated changes of arcuate proopiomelanocortin (POMC) neuronal excitability by
      using whole-cell recording. One cellular mechanism by which estrogen increases
      neuronal excitability is to desensitize (uncouple) gamma-aminobutyric acid type B
      (GABA(B)) receptors from their G-protein-gated inwardly rectifying K(+) channels
      in hypothalamic neurons. We found that the PI3K inhibitors wortmannin and
      LY294002 significantly reduced the estrogen-mediated GABA(B) receptor
      desensitization in POMC arcuate neurons, suggesting that PI3K signaling is a
      critical downstream mediator of the estrogen-mediated rapid effects.
      Collectively, these data suggest that the interplay between estrogen and PI3K
      occurs at multiple levels, including transcriptional and membrane-initiated
      signaling events that ultimately lead to changes in homeostatic function.

PMID- 18085587
TI  - Manipulative therapy of secondary lymphedema in the presence of locoregional
      tumors.
AB  - BACKGROUND: Complete decongestive therapy (CDT), including manual lymphatic
      drainage (MLD) is a manipulative intervention of documented benefit to patients
      with lymphedema (LE). Although the role of CDT for LE is well described, to the
      authors' knowledge there are no data regarding its efficacy for patients with LE
      due to tumor masses in the draining anatomic bed. Traditionally, LE therapists
      are wary of providing therapy to such patients with 'malignant' LE for fear of
      exacerbating the underlying cancer, and that the obstruction will render therapy
      less effective. In the current study, the authors' experience providing CDT for
      such patients is discussed. METHODS: Cancer survivors with LE were referred to
      therapists at 2 Atlanta-area clinics. CDT consists of treatment (Phase 1) and
      maintenance phases (Phase 2). During Phase 1, the patient undergoes manipulative
      therapy and bandaging daily until the LE reduction plateaus; at that point, Phase
      2 (self-care) begins. At the beginning and end of Phase 1, LE is quantified and
      differences in girth volume calculated. The results for patients completing Phase
      1 therapy for LE in the presence of locoregional masses were compared with
      results for patients with LE in the absence of such disease. Both volume
      reduction of the affected limb and number of treatments to plateau were analyzed.
      RESULTS: Between January 2004, and March 2007, LE of 82 limbs in 72 patients was
      treated with CDT and Phase 1 was completed. The median number of treatments to
      plateau was 12 (range, 4-23 treatments); the median limb volume reduction was 22%
      (range, -23 to 164%). Nineteen limbs (16 patients) with associated chest
      wall/axillary or pelvic/inguinal tumors had nonsignificant difference in LE
      reduction (P = .75) in the presence of significantly more sessions to attain
      plateau (P = .0016) compared with 63 limbs in 56 patients without such masses.
      CONCLUSIONS: Patients with LE may obtain relief with CDT regardless of whether
      they have locoregional disease contributing to their symptoms. However, it will
      likely take longer to achieve that effect. Manipulative therapy of LE should not
      be withheld because of persistent or recurrent disease in the draining anatomic
      bed.

PMID- 18085588
TI  - Differential localization of GABAA receptor subunits within the substantia nigra
      of the human brain: an immunohistochemical study.
AB  - Gamma-aminobutyric acid(A) (GABA(A)) receptors (GABA(A)R) are inhibitory
      heteropentameric chloride ion channels comprising a variety of subunits and are
      localized at postsynaptic sites within the central nervous system. In this study
      we present the first detailed immunohistochemical investigation on the regional,
      cellular, and subcellular localisation of alpha(1), alpha(2), alpha(3),
      beta(2,3), and gamma(2) subunits of the GABA(A)R in the human substantia nigra
      (SN). The SN comprises two major regions, the SN pars compacta (SNc) consisting
      of dopaminergic projection neurons, and the SN pars reticulata (SNr) consisting
      of GABAergic parvalbumin-positive projection neurons. The results of our single-
      and double-labeling studies demonstrate that in the SNr GABA(A) receptors contain
      alpha(1), alpha(3), beta(2,3), and gamma(2) subunits and are localized in a
      weblike network over the cell soma, dendrites, and spines of SNr parvalbumin
      positive nonpigmented neurons. By contrast, GABA(A)Rs on the SNc dopaminergic
      pigmented neurons contain predominantly alpha(3) and gamma(2) subunits; however
      there is GABA(A)R heterogeneity in the SNc, with a small subpopulation (6.5%) of
      pigmented SNc neurons additionally containing alpha(1) and beta(2,3) GABA(A)R
      subunits. Also, in the SNr, parvalbumin-positive terminals are adjacent to
      GABA(A)R on the soma and proximal dendrites of SNr neurons, whereas linear
      arrangements of substance P-positive terminals are adjacent to GABA(A) receptors
      on all regions of the dendritic tree. These results show marked GABA(A)R subunit
      hetereogeneity in the SN, suggesting that GABA exerts quite different effects on
      pars compacta and pars reticulata neurons in the human SN via GABA(A) receptors
      of different subunit configurations.

PMID- 18085589
TI  - Repopulation of cochlear macrophages in murine hematopoietic progenitor cell
      chimeras: the role of CX3CR1.
AB  - Cochlear macrophages have been shown to accumulate in the murine cochlea
      following acoustic trauma. This investigation was performed to determine whether
      cochlear macrophages could be replaced by donor transplantation of bone marrow
      precursors. Lethally irradiated C57BL/6 mice were transplanted with hematopoietic
      precursors from CX3CR1(GFP/GFP) fetal mice. CX3CR1(GFP/GFP) mice express green
      fluorescent protein (GFP) in monocytes and macrophages and possess no functional
      CX3CR1. Donor monocytes and macrophages can be easily traced in the wild-type
      recipient with fluorescent microscopy. We studied mice at 2-16 weeks after
      transplantation to assess repopulation of cochlear macrophages. A separate group
      of chimeras was exposed to octave band noise (8-16 kHz for 2 hours) 2 weeks after
      transplantation to evaluate the migration properties of donor hematopoietic
      precursors. We found that macrophages derived from donor hematopoietic precursors
      appeared in cochlea 3-4 weeks after transplantation and increased week by week.
      Noise exposure induced a massive accumulation of leukocytes, particularly in the
      spiral ligament of the basal turn. There was no difference between
      CX3CR1(GFP/GFP) donor/wild-type recipient chimeras and the wild-type donor/wild
      type recipient chimeras in hearing thresholds, accumulation of cochlear
      macrophages, or tissue injury after noise exposure. These data indicate that
      cochlear macrophages are derived from bone marrow precursors and that they are an
      exchanging and migratory population. Furthermore, CX3CR1 in hematopoietic
      precursors is not necessary for macrophage migration into cochlea and when
      deleted in this cell population, the absence of CX3CR1 does not substantially
      effect the outcomes after noise.

PMID- 18085590
TI  - Disparities in participation in cancer clinical trials in the United States : a
      symptom of a healthcare system in crisis.
AB  - Disparities in minorities' representation in cancer clinical trials have been
      shown only in adult populations, which suggest that the main causes of these
      disparities relate to health system-based barriers, including issues of poverty
      (lack of insurance), poor access to trials, and an inadequate number of clinical
      trials. Initiatives that increase the participation of community physicians in
      cancer clinical research trials and increase low socioeconomic status patients'
      access to cancer trials will likely ameliorate this problem.

PMID- 18085591
TI  - Enkephalin co-expression with classic neurotransmitters in the amygdaloid complex
      of the rat.
AB  - This study aimed at characterizing the neurotransmitter phenotype of enkephalin
      neurons in the rat amygdaloid complex. We first established the detailed
      distribution of vesicular glutamate transporters 1 and 2 (VGLUT1 and -2) and
      glutamate decarboxylase 65 (GAD65) in the amygdala by using in situ
      hybridization. In the amygdaloid complex, GAD65 is strongly expressed in striatal
      like divisions, namely, the anterior amygdaloid area, the central nucleus (CEA),
      the intercalated nuclei, and the dorsal part of the medial nucleus (MEA). VGLUT1
      and -2 expression is mostly segregated to specific divisions of the amygdale,
      with VGLUT2 being expressed only in the MEA, the anterior cortical nucleus
      (COAa), and the anterior basomedial nucleus (BMAa), whereas VGLUT1 is expressed
      in all other divisions of the amygdala. Second, we assessed the co-expression of
      preproenkephalin (ppENK) with GAD65, VGLUT1, or VGLUT2 by using double
      fluorescent in situ hybridization. We found that ppENK mRNA co-localized
      exclusively with GAD65 in all striatal-like structures of the amygdaloid complex
      with the exception of the MEA, where ENK also co-localized with VGLUT2 mRNA. This
      co-localization is most apparent in the posteroventral part of the MEA, where 70%
      of ENKergic cells expressed VGLUT2. In addition, ppENK also co-localized with
      VGLUT1 because more than 95% of ENK cells in the basolateral amygdala expressed
      VGLUT1. In contrast, less than 25% of ENKergic cells expressed VGLUT1 in the
      lateral nucleus of the amygdale, with the majority of ENK cells expressing GAD65
      mRNA in this nucleus. These results have broad implications for understanding the
      functional roles of enkephalinergic neurotransmission in the amygdaloid complex.

PMID- 18085592
TI  - Bulbospinal neurons of the rat rostromedial medulla are highly collateralized.
AB  - The rostromedial medulla participates in a large variety of sensory, motor, and
      autonomic functions. We asked whether individual bulbospinal neurons in this
      region have localized, target-specific terminal arbors or whether they
      collateralize broadly in the spinal cord. Collateralization was quantified along
      three spinal axes, rostrocaudal, left-right, and dorsoventral, by using double
      retrograde labeling. Fluorogold was applied to one target, and cholera toxin B
      chain (CTB) was applied to the second. We determined the prevalence of neurons
      that retrogradely label with both tracers in the constituent nuclei of the
      rostromedial medulla, the raphe nuclei, the gigantocellular reticular nucleus
      (Gi, bilaterally), the Gi pars alpha (GiA, bilaterally), and the midline
      medullary reticular formation. A large fraction of neurons in each of these
      nuclei had bulbospinal projections, ranging from > or =56% for the raphe nuclei
      to > or =14% for the Gi. For reasons discussed, these values are probably
      underestimates. Most of the neurons that projected to the lumbar spinal cord also
      projected to the cervical cord. Likewise, most neurons that projected to the
      ventral horn also had a collateral branch in the dorsal horn. However, relatively
      few had bilateral projections; most projected ipsilaterally or contralaterally. A
      considerable degree of collateralization was also seen among vestibulospinal
      neurons. The high level of collateralization of the descending projections of the
      rostromedial medulla suggests that neurons in this area ultimately act on
      peripheral target tissues or functions that are widely distributed in the body,
      or that they play a generalized modulatory role across functional modalities,
      rather than playing specific topographically delimited roles.

PMID- 18085593
TI  - Molecular characterization and comparative localization of the mRNAs encoding two
      glutamic acid decarboxylases (GAD65 and GAD67) in the brain of the African
      lungfish, Protopterus annectens.
AB  - The existence of two distinct genes encoding two isoforms of glutamic acid
      decarboxylase (GAD65 and GAD67) has been demonstrated in most vertebrate classes,
      yet little is known about their differential distributions and functions in the
      central nervous system in nonmammalian vertebrates. In the present study, we have
      partially sequenced the cDNAs encoding GAD65 and GAD67 in the lungfish
      Protopterus annectens and determined their relative distributions in the adult
      brain by in situ hybridization histochemistry. The expression patterns of the
      GAD65 and GAD67 mRNAs were globally similar; the highest expression levels being
      observed in the granular layer of the olfactory bulb, the pallium, the
      subpallium, the anterior preoptic area, the thalamus, the hindbrain central gray,
      and the rhombencephalic visceral areas. However, striking differential expression
      was noticed in several structures. Very high to high concentrations of GAD67 mRNA
      were seen in the dorsal and ventral aspects of the anterior olfactory nucleus,
      which is in marked contrast to the very low expression of GAD65 in this region.
      Similarly, high levels of GAD67 mRNA were observed in the intermediate and
      ventral parts of the medial pallium that were virtually devoid of GAD65 mRNA. In
      contrast, GAD65 mRNA was found in the periaqueductal gray that did not express
      GAD67 mRNA. The differential expression of GAD65 and GAD67 mRNAs in these regions
      of the lungfish CNS indicates that the two GAD isoforms can be differentially
      regulated and that they may have distinct physiological roles.

PMID- 18085595
TI  - A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone
      refractory prostate cancer who are refractory to docetaxel.
AB  - BACKGROUND: Prostate cancer is the second leading cause of cancer mortality among
      men in the U.S. To the authors' knowledge, there is no proven, effective, second
      line therapy for docetaxel-refractory disease. Recent data suggest that platinum
      salts may be effective when combined with taxanes in metastatic hormone
      refractory prostate cancer (HRPC). The authors conducted a phase 2 trial of
      docetaxel plus carboplatin chemotherapy in this disease setting. METHODS:
      Eligible men had metastatic HRPC that had progressed during or within 45 days
      after the completion of docetaxel-based chemotherapy. Patients were treated with
      intravenous docetaxel at a dose of 60 mg/m(2) plus carboplatin at an area under
      the curve of 4 once every 21 days until they had either disease progression or
      unacceptable toxicity. RESULTS: Thirty-four patients were enrolled. Therapy was
      tolerated reasonably well; Grade 3 leukopenia (graded according to the Common
      Toxicity Criteria grading system) was the most common adverse event (experienced
      by 56% of patients), but there was only 1 episode of febrile neutropenia
      reported. Prostate-specific antigen (PSA) declines > or =50% were noted in 18% of
      patients, and measurable responses were observed in 14%. The median duration of
      PSA response was 5.7 months. The median progression-free survival was 3 months,
      and the median overall survival was 12.4 months. Patients were more likely to
      respond to the combination if they previously had responded to docetaxel.
      CONCLUSIONS: In men with HRPC who developed progressive disease during or shortly
      after treatment with docetaxel, the addition of carboplatin resulted in modest
      additional activity. Taxane-refractory HRPC is an area of unmet need, and the
      current trial has provided evidence that platinum chemotherapy may be an
      important therapeutic option.

PMID- 18085596
TI  - Measuring fatigue among women with Sjogren's syndrome or rheumatoid arthritis: a
      comparison of the Profile of Fatigue (ProF) and the Multidimensional Fatigue
      Inventory (MFI).
AB  - BACKGROUND: Fatigue is common in both Sjogren's syndrome (SS) and rheumatoid
      arthritis (RA) and can restrict functioning. AIMS: We tested the convergent
      validity of the Profile of Fatigue (ProF) using the Multidimensional Fatigue
      Inventory (MFI) in SS and RA. METHODS: The 16-item ProF and the 20-item MFI were
      completed by 82 White-British women aged 35-79 years (mean 60.4 years). Thirty
      four had been diagnosed with SS for a mean of 7.0 years and 48 had been diagnosed
      with RA for a mean of 14.5 years. The ProF measures four somatic facets of
      fatigue and two mental facets; the MFI contains one mental and four somatic
      facets. The structures of the items from both measures were tested by principal
      component factor analysis using varimax rotation. RESULTS: No significant
      differences in fatigue were found between the women with SS or RA. Five factors
      explained a total of 76% of the variance of the MFI; six factors explained 94% of
      the variance of the ProF. Mental fatigue items from both questionnaires loaded
      onto separate factors from somatic fatigue items; the two original facets of
      mental fatigue in the ProF were replicated. The four somatic fatigue facets of
      the ProF were generally replicated but the somatic facets of the MFI did not
      replicate as clearly. Equivalent facets correlated well between the two
      questionnaires (r >or= 0.65). CONCLUSIONS: Both the ProF and the MFI distinguish
      between somatic and mental fatigue in SS and RA but the ProF appears better at
      resolving somatic facets of fatigue.

PMID- 18085594
TI  - Expression of receptors for glial cell line-derived neurotrophic factor family
      ligands in sacral spinal cord reveals separate targets of pelvic afferent fibers.
AB  - Nerve growth factor has been proposed to mediate many structural and chemical
      changes in bladder sensory neurons after injury or inflammation. We have examined
      the expression of receptors for the glial cell line-derived neurotrophic factor
      (GDNF) family within sensory terminals located in the sacral spinal cord and in
      bladder-projecting sacral dorsal root ganglion neurons of adult female Sprague
      Dawley rats. Nerve fibers immunolabelled for GFRalpha1 (GDNF receptor), GFRalpha2
      (neurturin receptor), or GFRalpha3 (artemin receptor) showed distinct
      distribution patterns in the spinal cord, suggesting separate populations of
      sensory fibers with different functions: GFRalpha1-labeled fibers were in outer
      lamina II and the lateral-collateral pathway and associated with autonomic
      interneurons and preganglionic neurons; GFRalpha2-labeled fibers were only in
      inner lamina II; GFRalpha3-labeled fibers were in lamina I, the lateral
      collateral pathway, and areas surrounding dorsal groups of preganglionic neurons
      and associated interneurons. Immunofluorescence studies of retrogradely labelled
      bladder-projecting neurons in sacral dorsal root ganglia showed that
      approximately 25% expressed GFRalpha1 or GFRalpha3 immunoreactivity, the
      preferred receptors for GDNF and artemin, respectively. After cyclophosphamide
      induced bladder inflammation, fluorescence intensity of GFRalpha1-positive fibers
      increased within the dorsal horn, but there was no change in the GFRalpha2- or
      GFRalpha3-positive fibers. These studies have shown that GDNF and artemin may
      target bladder sensory neurons and potentially mediate plasticity of sacral
      visceral afferent neurons following inflammation. Our results have also revealed
      three distinct subpopulations of sensory fibers within the sacral spinal cord,
      which have not been identified previously using other markers.

PMID- 18085597
TI  - Lead exposure during development results in increased neurofilament
      phosphorylation, neuritic beading, and temporal processing deficits within the
      murine auditory brainstem.
AB  - Low-level lead (Pb) exposure is a risk factor for learning disabilities,
      attention deficit hyperactivity disorder (ADHD), and other neurological
      dysfunction. It is not known how Pb produces these behavioral deficits, but low
      level exposure during development is associated with auditory temporal processing
      deficits in an avian model, while hearing thresholds remain normal. Similar
      auditory processing deficits are found in children with learning disabilities and
      ADHD. To identify cellular changes underlying this functional deficit, Pb-induced
      alterations of neurons and glia within the mammalian auditory brainstem nuclei
      were quantified in control and Pb-exposed mice at postnatal day 21 by using
      immunohistochemistry, Western blotting, and 2D gel electrophoresis. Pb-treated
      mice were exposed to either 0.1 mM (low) or 2 mM (high) Pb acetate throughout
      gestation and through 21 days postnatally. Pb exposure results in little change
      in glial proteins such as glial fibrillary acidic protein (GFAP), myelin basic
      protein (MBP), or F4/80 as determined by Western blot analysis and
      immunohistochemistry. In contrast, Pb exposure alters neuronal structural
      proteins by inducing increased phosphorylation of both the medium (NFM) and high
      weight (NFH) forms of neurofilament within auditory brainstem nuclei. Axons
      immunolabeled for neurofilament protein show neuritic beading following Pb
      exposure both in vivo and in vitro, suggesting that Pb exposure also impairs
      axonal transport. Functional assessment shows no significant loss of peripheral
      function, but does reveal impairments in brainstem conduction time and temporal
      processing within the brainstem. These results provide evidence that Pb exposure
      during development alters axonal structure and function within brainstem auditory
      nuclei.

PMID- 18085598
TI  - Theory and evidence to explain guidelines, variation, and risk of unwanted
      influence.

PMID- 18085599
TI  - Physician peer assessments for compliance with methadone maintenance treatment
      guidelines.
AB  - INTRODUCTION: Medical associations and licensing bodies face pressure to
      implement quality assurance programs, but evidence-based models are lacking. To
      improve the quality of methadone maintenance treatment (MMT), the College of
      Physicians and Surgeons of Ontario, Canada, conducts an innovative quality
      assurance program on the basis of peer assessments. Using data from this program,
      we assessed physician compliance with MMT guidelines and determined whether
      physician factors (e.g., training, years of practice), practice type, practice
      location, and/or caseload is associated with MMT guideline adherence. METHODS:
      Secondary analysis of methadone practice assessment data collected by the College
      of Physicians and Surgeons of Ontario, Canada. Assessment data from methadone
      prescribing physicians who completed their first year of methadone practice were
      analyzed. We calculated the mean percentage compliance per guideline per
      physician and global compliance across all guidelines per physician. Linear
      regression was used to assess factors associated with compliance. RESULTS: Data
      from 149 physician practices and 1,326 patient charts were analyzed. Compliance
      across all charts was greater than 90% for most areas of care. Compliance was
      less than 90% for take-home medication procedures; urine toxicology screening;
      screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human
      immunodeficiency virus (HIV), tuberculosis, other sexually transmitted
      infections, and completion of a psychosocial assessment. Mean global compliance
      across all charts and guidelines per physician was 94.3% (standard deviation =
      7.4%) with a range of 70% to 100%. Linear regression analysis revealed that only
      year of medical school graduation was a significant predictor of physician
      compliance. DISCUSSION: This is the first report of MMT peer assessments in
      Canada. Compliance is high. Few countries conduct similar assessment processes;
      none report physician-level results. We cannot quantify the contribution of peer
      assessment, training, or self-selection to the compliance rates, but compared to
      other areas of practice these rates suggest that peer assessment may exert a
      significant effect on compliance. A similar assessment process may in other areas
      of clinical practice improve physician compliance.

PMID- 18085600
TI  - The role of collegial interaction in continuing professional development.
AB  - INTRODUCTION: Many physicians seek information from colleagues over other
      sources, highlighting the important role of interaction in continuing
      professional development (CPD). To guide the development of CPD opportunities,
      this study explored the nature of cancer-related questions faced by general
      surgeons, and how interaction with colleagues addressed those questions. METHODS:
      This study involved thematic analysis of field notes collected through
      observation and transcripts of telephone interviews with 20 surgeons, two
      pathologists, one medical oncologist, and one radiation oncologist affiliated
      with six community hospitals participating in multidisciplinary cancer
      conferences by videoconference in one region of Ontario, Canada. RESULTS: Six
      multidisciplinary cancer conferences (MCCs) were observed between April and
      September 2006, and 11 interviews were conducted between December 2006 and
      January 2007. Sharing of clinical experience made possible collective decision
      making for complex cancer cases. Physicians thought that collegial interaction
      improved awareness of current evidence, patient satisfaction with treatment
      plans, appropriate care delivery, and continuity. By comparing proposed treatment
      with that of the group and gaining exposure to decision making for more cases
      than they would see in their own practices, physicians developed clinical
      expertise that could be applied to future cases. Little collegial interaction
      occurred outside these organized sessions. DISCUSSION: These findings highlight
      the role of formally coordinated collegial interaction as an important means of
      CPD for general surgeons. Investment may be required for infrastructure to
      support such efforts and for release of health professional time for
      participation. Further research is required to examine direct and indirect
      outcomes of collegial interaction.

PMID- 18085601
TI  - Use of personal digital assistants (PDAs) in reflection on learning and practice.
AB  - INTRODUCTION: As the use of personal digital assistants (PDAs) grows, the value
      of reflection of learning and practice draws increased attention from
      policymakers and evaluators. To learn more about the use of PDAs in practice and
      learning, the present study describes use of (1) PDAs in patient care and (2) a
      PDA version of the Virginia Board of Medicine Continuing Competency and
      Assessment Form (CCAF), a learning portfolio intended to encourage documentation
      of reflection on practice and medical education. METHODS: A purposive sample of
      10 practicing physicians (6 male, 7 primary care) was recruited from geographic
      regions throughout Virginia. Five participants were previous users of a PDA.
      Three sources of data were analyzed: (1) a questionnaire describing PDA usage,
      (2) transcripts from telephone interviews, and (3) CCAF written comments. A study
      team member installed the PDA system and conducted individualized training on the
      basis of current equipment, software, and skills of the learner. Telephone
      interviews were completed 4-6 months after training. RESULTS: All physicians
      accessed the system after training. Use of the PDA was associated with the value
      of information for making clinical decisions. Information accessed by PDA was
      used not only for clinical decisions but also for patient education and for
      teaching medical students. Use of the CCAF prompted physicians to reflect on
      changes in clinical practice. DISCUSSION: Training on the handheld equipment and
      applications should include assessment of systems connectivity and integration,
      access authority, existing skills, and previous use. Proponents of PDA use for
      clinical decisions should assure access to information that is useful to
      physicians for reflection on learning and practice.

PMID- 18085602
TI  - Evaluation of an interprofessional continuing professional development initiative
      in primary health care.
AB  - INTRODUCTION: Interest in collaborative care approaches and in interprofessional
      education (IPE) to prepare providers for interprofessional collaboration is
      increasing and particularly so in the field of primary health care. Although
      evidence for the effectiveness of IPE is mixed, Barr et al. (2005) have proposed
      a useful framework for evaluating six levels of IPE outcomes. The Building a
      Better Tomorrow Initiative (BBTI) was a continuing professional development (CPD)
      program established to enhance the collaborative competencies of primary health
      care providers and foster interprofessional collaboration in primary health care
      settings. This article describes the evaluation design, specific measures, and
      educational outcomes of the BBTI program using Barr and colleagues' evaluation
      framework. METHODS: We used a mixed method approach. The evaluation research
      design was a one-group, pre- to poststudy utilizing a combination of quantitative
      and qualitative evaluation instruments and methods to collect data for the six
      levels of the Barr et al. evaluation framework. Evaluation focused especially on
      the following levels: participant satisfaction (reaction), confidence change
      (attitudes), performance change, and organizational impact. RESULTS: Participants
      were very satisfied with the BBTI modules and reported significant increases in
      their confidence and interprofessional collaborative competencies upon return to
      their primary health care practice sites. Interviews and focus groups with
      participants and administrators suggest that the BBTI modules were also effective
      in promoting and fostering interprofessional collaboration within primary health
      care settings. DISCUSSION: Results suggest that interprofessional CPD is
      effective in enhancing understanding of the roles of other professions, fostering
      respect and positive attitudes toward interprofessional collaboration, developing
      collaborative competencies, and promoting organizational change.

PMID- 18085603
TI  - A risk stratification tool to assess commercial influences on continuing medical
      education.
AB  - INTRODUCTION: Heightened concerns about industry influence on continuing medical
      education (CME) have prompted tighter controls on the management of commercial
      funding and conflict of interest. As a result, CME providers must closely monitor
      their activities and intervene if bias or noncompliance with accreditation
      standards is likely. Potential for industry influence can be difficult to assess
      at a stage in the planning process when mitigation strategies can assure balance
      and content validity. Few tools exist to aid providers in this regard. METHODS: A
      12-item instrument was designed to assess risk for commercial influence on CME.
      To determine reliability and validity, a cohort of experienced CME professionals
      applied the tool to standardized "cases" representing CME activities in the early
      stages of planning. Results were compared with the experts' assignment of the
      same cases to one of four risk categories. A survey of study participants was
      conducted to ascertain usefulness and potential applications of the tool.
      RESULTS: Analysis demonstrated strong intraclass correlation across cases (0.90),
      interrater reliability (94%), and correlation between assessment of risk with and
      without the tool (Spearman coefficient, 0.93, p < 0.01; weighted kappa, 0.59).
      Participants found the tool easy to use and of potential benefit to their CME
      office. DISCUSSION: The Consortium for Academic Continuing Medical Education
      (CACME) risk stratification tool can help CME providers identify activities that
      must be closely monitored for potential industry influence, remain aware of
      factors that place programming at risk for noncompliance with accreditation
      standards, and substantiate the allocation of resources by the CME office.

PMID- 18085604
TI  - Integrating continuing professional development and graduate curriculum in a case
      based interprofessional online course: telemedicine in action.

PMID- 18085605
TI  - Spatiotemporal localization of VEGF-A isoforms in the mouse postnatal growth
      plate.
AB  - Vascular endothelial growth factor (VEGF) is implicated as a key angiogenic
      factor in the development of endochondral long bone. Several studies have
      evaluated the role of VEGF in prenatal endochondral bone development, but few
      have evaluated VEGF postnatally. Growth plates from mice at postnatal ages 14
      (P14), 35 (P35), 49 (P49), and 77 (P77) days were examined for differential
      expression of the primary VEGF-A mRNA isoforms: VEGF 120, VEGF 164, and VEGF 188.
      VEGF 120 isoform expression was stable across all ages, whereas VEGF 164 had
      significantly less expression at P35 and P49 and VEGF l88 expression increased
      with increasing age. The proportion of transcript isoforms expressed at a given
      age also changed with VEGF 120 being expressed more highly at P35 and P49 than
      the other two isoforms. Changes in VEGF mRNA isoforms across cell types within
      the growth plate were assessed by Percoll fractionation of growth plate cells at
      age P28. Cells of the proliferative and early hypertrophic regions had
      significantly higher total VEGF mRNA expression relative to the resting and late
      hypertrophic regions. VEGF protein expression assessed by immunohistochemistry
      showed variable expression patterns with increasing postnatal age. In contrast,
      FLK-1 (VEGF Receptor-2) expression was restricted to the hypertrophic region.
      These results indicate that VEGF continues to play a significant role in
      endochondral bone development throughout the entire growth phase of postnatal
      bone development.

PMID- 18085606
TI  - Effect of y2 receptor deletion on whole bone structural behavior in mice.
AB  - Recent evidence has shown that mice deficient in the NPY Y2 receptor have an
      increase in trabecular bone volume as well as cortical bone mass due to increased
      osteoblast activity. However, the mechanical phenotype of Y2 -/- bone has not yet
      been assessed. Thus, the aim of the present study was to examine the effect of Y2
      deletion on murine cortical bone structural behavior, as well as to assess the
      material and geometric contributions to that behavior. The results of this study
      indicate that Y2 -/- mice on a 129 SV x Balb/c background strain are smaller in
      body mass and have smaller bones than wild-type controls. As expected based on
      smaller bone cross-sectional properties, cortical bone structural strength was
      lower in -/- animals. Surprisingly, the structural stiffness of -/- bones was
      comparable to that of +/+ bones despite their smaller cross-sectional geometry.
      Comparable structural stiffness appeared to be achieved by means of an elevated
      effective shear modulus, which was associated with a small, but statistically
      significant, higher ash content in Y2 -/- bones. These data represent the first
      comprehensive characterization of the effect of Y2 deletion on cortical bone
      structural and material behavior to date.

PMID- 18085607
TI  - Versican knock-down compromises chondrogenesis in the embryonic chick limb.
AB  - Mesenchymal cell aggregation is critical for cartilage formation in the
      vertebrate limb. The extracellular matrix (ECM) plays a critical role in
      governing cell behavior and cell phenotype in this tissue, and the hyalectin
      versican is highly expressed in the ECM of precartilage mesenchymal cells and
      developing synovial joints. Although several in vitro studies have been conducted
      in an attempt to address versican's role during limb mesenchymal condensation,
      factors such as differences in cell density in culture, variations between
      chondrogenic cell lines, and the inability to prolong the viability of limb
      explants have led to conflicting data, mandating an in vivo analysis. By using a
      morpholino directed strategy in ovo, we performed knock-down of versican
      expression in the presumptive ulnar region of the developing chick wing at time
      points critical to skeletogenesis. These data indicate that in ovo misexpression
      of versican compromised mesenchymal condensation with resulting ulnar cartilages
      reduced in length distally by an average of 53% relative to contralateral control
      limbs. In select versican morphants the olecranon process was also reduced in
      size proximally and failed to cup the humerus, likely impairing joint
      morphogenesis. This study represents the first report assessing the role of
      versican in the developing chick limb in ovo, further demonstrating the
      importance of versican proteoglycan expression during chondrogenesis and
      extending previous findings to suggest a role for versican during synovial joint
      development.

PMID- 18085608
TI  - Evolution, development, and initial function of the mammalian neocortex: response
      of the germinal zones to endothermy.
AB  - In the mouse the release of neocortical neurons from the periventricular germinal
      layers of the forebrain commences towards the ventral margin of the lateral
      pallium at the level of the interventricular foramen and is propagated from there
      across the lateral wall of the hemisphere. In the adult cortex the origin of the
      gradient corresponded to the ventral portion of the somatotopic map of the body,
      that is, to the area representating structures derived from the embryonic
      branchial arches, namely, the peri-oral region and laryngo-pharyngeal masticatory
      apparatus. Branchial arch nerves also innervate the fore- and mid-gut and all the
      related exocrine and endocrine glands. This suggests that the mammalian neocortex
      evolved from a visceral integration area in a positionally equivalent area in the
      pallium of a reptilian ancestor which expanded in relation to extensive changes
      taking place in the visceral and branchial systems of the body during the
      transition from reptilian ectothermy to mammalian endothermy. The practical
      problem facing early mammals was to acquire and process the extra energy required
      to sustain a continuously high metabolic rate. Improvements to the food
      processing capabilities of the visceral and branchial systems and the expansion
      of their neural control were important components in the conglomerate of changes
      required to sustain the increased energy demands of endothermic tissues.
      Endothermy also bestowed the ability to sustain greater numbers of metabolically
      expensive neurons and this, in turn, required an appropriate response from the
      cell production mechanisms in the periventricular germinal layers.

PMID- 18085609
TI  - Nigrostriatal neurons in rat express the glial cell line-derived neurotrophic
      factor receptor subunit c-RET.
AB  - The substantia nigra neurons expressing c-RET, a glial cell line-derived
      neurotrophic factor (GDNF) receptor intracellular tyrosine kinase subunit, were
      investigated in rats by using a double labeling method which combined retrograde
      horseradish peroxidase (HRP) labeling after injection into the striatum with
      immunohistochemistry to c-RET. It was revealed that the distribution of c-RET
      immunoreactive neurons and HRP-labeled nigrostriatal neurons overlapped. Numerous
      double-labeled HRP/c-RET neurons were found in the substantia nigra pars compacta
      with predominate distribution ipsilateral to the injected striatum.
      Semiquantitative cell count indicated that a large percentage (97%) of HRP
      labeled neurons showed c-RET immunoreactivity. Furthermore, double-labeled HRP/c
      RET ones constituted only 61% of total c-RET-immunoreactive neurons in the
      substantia nigra ipsolateral to the injected striatum. Taken together with
      previous observations on glial cell line-derived neurotrophic factor in the basal
      ganglia, this study provides evidence that the c-RET protein may mediate
      biological activity of GDNF family ligands in most of projecting neurons in the
      substantia nigra pars compacta where the dopaminergic neurons are numerously
      distributed. Specially, it suggests that c-RET-mediating signaling cascades may
      play important roles in neuron-glial interaction that support and sustain
      nigrostriatal neuronal circuits in the basal ganglia.

PMID- 18085610
TI  - Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia:
      need for new response definitions?
AB  - BACKGROUND: Response rates in chronic myeloid leukemia (CML) are now reported
      based on the cumulative incidence of a single-time best response. The study aim
      was to examine the significance of different response criteria for CML on
      imatinib therapy. METHODS: In all, 276 patients with chronic phase CML on
      imatinib therapy were analyzed. Cytogenetic and molecular responses were coded as
      to single best response and response at specific intervals of treatment. RESULTS:
      The cumulative incidence of complete cytogenetic response (CGCR) with imatinib
      was 91%; however, the incidence of CGCR at 48 months into therapy was only 78%.
      Similarly, the incidence of major molecular responses (best cumulative vs
      landmark at 48 months) were 74% versus 62%, and of undetectable BCR-ABL
      transcripts 38% versus 24%. There was a strong association between achievement of
      major cytogenetic response (Philadelphia chromosome [Ph]-positivity <or=35%) at 6
      months to 12 months and survival as well as progression-free survival (PFS).
      Achievement of major molecular response (vs lesser molecular response) in
      patients in complete cytogenetic response was not associated with significant
      differences in survival, but showed some association with PFS. Durable CGCR and
      major molecular responses (documented continuously for >or=12 months) were
      associated with longer PFS duration but not with survival duration differences.
      Of interest, major molecular responses documented at least twice were noted in
      71% of patients on imatinib therapy; undetectable BCR-ABL transcripts documented
      at least twice were noted in 34%. CONCLUSIONS: Achievement and durability of CGCR
      and of major and complete molecular responses at landmark times predict outcome
      in CML, and may help in comparing the efficacy of different treatments.

PMID- 18085611
TI  - Phase 2 study of gemcitabine in combination with rituximab in patients with
      recurrent or refractory Hodgkin lymphoma.
AB  - BACKGROUND: The management of recurrent or refractory Hodgkin lymphoma (HL)
      remains challenging. The objective of this phase 2 trial was to investigate the
      activity of gemcitabine in combination with rituximab in patients with recurring
      or refractory HL. METHODS: Patients were considered eligible if they had
      recurring or refractory HL, had received >or=2 prior chemotherapy regimens, had
      an Eastern Cooperative Oncology Group (ECOG) performance status <or=2, and had
      adequate organ function. Rituximab was administered at a dose of 375 mg/m2
      intravenously every week for 6 weeks. Gemcitabine was administered at a dose of
      1250 mg/m2 intravenously on Days 1 and 8, with a week of rest on Day 15 of 21-day
      cycles in outpatient settings. Response was assessed after 2 cycles of
      gemcitabine, and those patients who demonstrated a response continued to receive
      a maximum of 4 additional courses of gemcitabine. RESULTS: Thirty-three patients
      received the study drugs. The median age of patients was 32 years (range, 19-81
      years), and 55% of the patients previously underwent autologous stem cell
      transplantation. Grade 3 or 4 (graded according to the National Cancer Center
      Institute Common Toxicity Criteria [version 2.0]) toxic effects included
      neutropenia (36%) and thrombocytopenia (15%). Objective responses occurred in 16
      patients (48%). Responses were observed regardless of CD20 positivity in tumor
      cells. The median duration of failure-free survival was 2.7 months (range, 0.9
      18.3 months). Seven patients (21%) eventually proceeded to either autologous (n =
      2) or allogeneic (n = 5) stem cell transplantation. CONCLUSIONS: Combination
      therapy with gemcitabine and rituximab is active in previously treated patients
      with recurrent or refractory HL. The favorable safety profile and the ease of its
      administration in outpatient settings warrant investigating it further in
      combination with other active drugs.

PMID- 18085612
TI  - Hospital lymph node counts and survival after radical cystectomy.
AB  - BACKGROUND: Several studies suggest that patients in whom more lymph nodes are
      examined have improved survival after radical cystectomy for bladder cancer.
      Despite growing calls for using lymph node counts as a hospital quality
      indicator, it has not been established that hospitals that obtain more lymph node
      have better outcomes. METHODS: Using the national Surveillance, Epidemiology, and
      End Results (SEER)-Medicare linked database (1992-2003), all patients undergoing
      radical cystectomy for cancer were identified (n = 3603). Hospitals were ranked
      and sorted into 3 evenly sized groups: low (no patients with >or=10 lymph nodes
      removed), medium (up to 20% of patients), and high (greater than 20% of
      patients). Survival rates were assessed for each hospital group, adjusting for
      potentially confounding patient and hospital characteristics. RESULTS: On
      average, low lymph node count hospitals had higher observed mortality rates
      compared with high lymph node count hospitals (unadjusted hazards ratio [HR],
      1.25; 95% confidence interval [95% CI], 1.13-1.39). Low lymph node count
      hospitals tended to treat patients who were older, had more comorbidity, were of
      lower socioeconomic status, had higher admission acuity, and had lower procedure
      volumes. After adjusting for these differences, low lymph node count hospitals
      tended to have slightly higher mortality (adjusted HR, 1.12; 95% CI, 0.99-1.27),
      although this finding did not reach statistical significance. Similar findings
      were evident when other thresholds (lymph node counts >or=5, >or=14, and >or=20)
      were used. CONCLUSIONS: Hospitals with high lymph node counts tend to have higher
      survival rates after radical cystectomy for bladder cancer. However, this effect
      is modest and is explained, in large part, by confounding patient and hospital
      factors.

PMID- 18085613
TI  - Cytologic findings after fertility-sparing radical trachelectomy.
AB  - BACKGROUND: Radical trachelectomy is a surgical procedure intended to preserve
      fertility in patients with early-stage cervical carcinoma in which the cervix is
      amputated in continuity with the parametrium and upper vagina, thereby sparing
      the uterus and adnexa. Follow-up is performed with periodic cytology specimens.
      The objective of the current study was to analyze the cytologic findings after
      this novel procedure. METHODS: Isthmic and vaginal Papanicolaou-stained ThinPrep
      cytology specimens taken from patients after radical vaginal and abdominal
      trachelectomy were reviewed. The specimens were also analyzed for the presence of
      benign endocervical cells, lower uterine segment glandular cells, endometrial
      stromal cells, and endometrial cells. The findings were correlated with the
      original diagnosis and follow-up, which included subsequent cytology specimens
      and biopsies. RESULTS: Cytology specimens (n = 223) from 44 patients were
      included in this study. An endometrial component was identified in 131 of the
      cases (59%). Twenty-eight cases were diagnosed as abnormal in the original
      cytology examination. Twenty of these cases and 5 additional cases that were
      diagnosed cytologically as benign had subsequent biopsies. The biopsies confirmed
      the presence of a lesion in only 4 of 25 biopsies (3 low-grade squamous
      intraepithelial lesions and 1 adenosquamous carcinoma). All cases diagnosed as
      atypical glandular cells represented tubal metaplasia, lower uterine segment
      glandular cells, or endometrial stromal cells. CONCLUSIONS: Cytology specimens
      after trachelectomy frequently contain glandular cells from the lower uterine
      segment epithelium or endometrial stromal cells, which can lead to a misdiagnosis
      of atypical glandular cells of undetermined significance. Tubal metaplasia is
      also a potential pitfall in these specimens. Pathologists and gynecologic
      oncologists should be aware of the potential pitfalls in the surveillance of
      smears after trachelectomy.

PMID- 18085614
TI  - Special features of dermal melanocytes in white silky chicken embryos.
AB  - In the hyperpigmented Silky (SK) chicken, melanoblasts are neural crest cells
      that emigrate from the neural tube, migrate dorsolaterally, close to the ectoderm
      and medioventrally, reaching visceral regions of the embryo, as well as
      populating the dermis. In this work, we analyzed the morphology and distribution
      of melanocytic lineage cells in white SK embryos at later stages of development
      (6 to 19 days of incubation) focusing in the dermis of dorsal skin to
      characterize this ectopically located population. Melanoblasts and immature
      melanocytes are seen at all analyzed stages, some of them clearly proliferative,
      suggesting a possibility of continued renewal of the population. Mature, fully
      differentiated melanocytes are elongated cells with many long cytoplasmic
      processes, forming a meshwork in superficial dermis, below a layer of collagen
      and elastic fibers that seems to prevent melanocytic lineage cells from reaching
      the epidermis at these later stages. SK chicken is the only Gallus gallus breed
      to display this arrangement of dermal melanocytes. The distribution of
      melanocytes below the collagen layer, observed in regions covered by feathers, is
      clearly not related with structural coloration as in areas of bare skin. Other
      functions for this conserved trait in SK must be investigated.

PMID- 18085615
TI  - The development of duodenal microadenomas in FAP patients: the human correlate of
      the Min mouse.
AB  - The morphological changes associated with the adenoma-carcinoma sequence are well
      documented in the colorectum. Small intestinal carcinogenesis is thought to
      progress through a similar adenoma-to-carcinoma pathway, but there is a relative
      dearth of studies examining the associated morphological changes. The best-known
      mouse model of intestinal neoplasia, the multiple intestinal neoplasia (Min)
      mouse, has been criticized as a genetic model of intestinal neoplasia, as the
      majority of its tumours occur in the small intestine. We examined pancreatico
      duodenal resection specimens from seven familial adenomatous polyposis (FAP)
      patients. Serial sections of these were stained with haematoxylin and eosin for
      beta-catenin and its downstream target CD44, for BMPR1a, lysozyme, carbonic
      anhydrase II, and with MIB-1. Individual dysplastic crypts were isolated and
      mutations in the FAP (APC) gene compared between the top and bottom of the crypt.
      We found that: (a) duodenal microadenomas are extremely common in FAP patients;
      (b) these grow in the core of duodenal villi, forming lesions similar to those
      described in the Min mouse; (c) many lesions arise as monocryptal adenomas and
      grow by a process of crypt fission and branching; (d) migrating adenomatous cells
      lose their dysplastic phenotype as they migrate up the crypt villous axis; and
      (e) Paneth cells lose positional information. IN CONCLUSION: (a) the
      morphological similarity of adenomas in the Min mouse and human suggest the Min
      mouse is a good model of FAP; (b) duodenal adenomas in FAP originate in
      monocryptal adenomas and follow the 'bottom-up' rather than the 'top-down' model
      of morphogenesis; (c) early microadenomas show evidence of cellular
      differentiation; (d) defects in the positioning of Paneth cells suggests
      disruption of the EphB2:EphB3 receptor system.

PMID- 18085617
TI  - Surgical oncology: training for multidisciplinary cancer care.

PMID- 18085618
TI  - Quality assurance in surgical oncology: the tale of the Dutch rectal cancer TME
      trial.

PMID- 18085616
TI  - Using nuclear morphometry to predict the need for treatment among men with low
      grade, low stage prostate cancer enrolled in a program of expectant management
      with curative intent.
AB  - PURPOSE: We assessed the use of quantitative clinical and pathologic information
      to predict which patients would eventually require treatment for prostate cancer
      (CaP) in an expectant management (EM) cohort. EXPERIMENTAL DESIGN: We identified
      75 men having prostate cancer with favorable initial biopsy characteristics; 30
      developed an unfavorable biopsy (Gleason grade >6, >2 cores with cancer, >50% of
      a core with cancer, or a palpable nodule) requiring treatment and 45 maintained
      favorable biopsies throughout a median follow-up of 2.7 years. Demographic,
      clinical data and quantitative tissue histomorphometry determined by digital
      image analysis were analyzed. RESULTS: Logistic regression (LR) modeling
      generated a quantitative nuclear grade (QNG) signature based on the enrollment
      biopsy for differentiation of Favorable and Unfavorable groups using a variable
      LR selection criteria of P(z)<0.05. The QNG signature utilized 12 nuclear
      morphometric descriptors (NMDs) and had an area under the receiver operator
      characteristic curve (ROC-AUC) of 87% with a sensitivity of 82%, specificity of
      70% and accuracy of 75%. A multivariable LR model combining QNG signature with
      clinical and pathological variables yielded an AUC-ROC of 88% and a sensitivity
      of 81%, specificity of 78% and accuracy of 79%. A LR model using prostate volume,
      PSA density, and number of pre-diagnosis biopsies resulted in an AUC-ROC of 68%
      and a sensitivity of 85%, specificity of 37% and accuracy of 56%. CONCLUSIONS:
      QNG using EM prostate biopsies improves the predictive accuracy of LR models
      based on traditional clinicopathologic variables in determining which patients
      will ultimately develop an unfavorable biopsy. Our QNG-based model must be
      rigorously, prospectively validated prior to use in the clinical arena.

PMID- 18085619
TI  - Histopathological response after preoperative radiochemotherapy in rectal
      carcinoma is associated with improved overall survival.
AB  - BACKGROUND: Recent studies showed improved local control after preoperative
      radiochemotherapy (RCTX) in patients with locally advanced rectal carcinoma, but
      failed to demonstrate a survival benefit. Our aims were to determine outcome and
      impact of histopathological response after preoperative RCTX. METHODS: One
      hundred four patients with uT3 rectal carcinoma were treated with preoperative
      RCTX of 45 Gy and continuous 5-FU infusion between 1997 and 2001 (group I).
      Histopathological response was evaluated in all specimens after tumor resection.
      Group II consisted of 114 patients with uT3 rectal carcinoma treated with
      postoperative RCTX between 1988 and 1997. RESULTS: Group I showed a 6.1% 5-year
      local recurrence rate compared to 15.3% in group II (P = 0.023). Overall survival
      rates did not differ significantly between both groups (P = 0.225).
      Histopathological responders had a significantly improved 5-year overall survival
      with 89.1 (7.8)% compared to 68.7 (6.7)% of the non-responders (P = 0.008) and
      were identified as an independent prognostic factor. CONCLUSIONS: Significant
      improvement of overall survival was observed for histopathological tumor
      responders after neoadjuvant radiochemotherapy. Our protocol of preoperative
      radiochemotherapy confirms the results of the multi-center studies in regard to
      local control and overall survival.

PMID- 18085620
TI  - Retroperitoneoscopic adrenalectomy: lateral versus dorsal approach.
AB  - BACKGROUND: For tumours of the adrenal gland different surgical retroperitoneal
      approaches have been established, including the lateral and the dorsal approach.
      It is still unclear if the lateral or the dorsal approach should be preferred.
      PATIENTS AND METHODS: A retrospective comparison between 21 patients who
      underwent retroperitoneoscopic adrenalectomy in lateral position (LRA) and 24
      patients who underwent a retroperitoneoscopic adrenalectomy in dorsal position
      (DRA). RESULTS: There were no significant differences with regard to the age,
      sex, tumour localisation, and the size of the tumour. The body-mass-index as well
      as the operation time was significantly higher of patients who underwent surgery
      in lateral position. Complications were comparable in both groups. CONCLUSION:
      The dorsal and the lateral retroperitoneal approach are ideal approaches for
      patients having had an intraabdominal surgery before. Due to the missing
      intraabdominal pressure the lateral approach is advantageous for patients with
      high body-mass-index (>35) and is indicated for patients with a tumour >6 cm due
      to the small retroperitoneal space.

PMID- 18085621
TI  - T0 N1 adenocarcinoma of the colon following oxaliplatin-based neoadjuvant
      chemotherapy.

PMID- 18085622
TI  - Development of the mucosal vascular system in the distal colon of the fetal
      mouse.
AB  - The formation of the crypt in the distal colon of the mouse was investigated in
      association with the development of vascular networks. For histological
      observation, 1-microm cross-sections were made from the distal colon of fetal
      mice in 13 to 18 days of gestation. Three-dimensional distributions of vascular
      networks in the organ were observed after perfusing fetuses with rhodamine
      isothiocyanate-labeled gelatin and immunostaining for laminin to examine the
      boundary between the epithelium and the mesenchyme. At 13 days of gestation, the
      distal colon and its epithelium formed a cylindrical tube and a loose primary
      plexus of vessels was built in the mesenchyme. In the distal colon of 15 days of
      gestation, the caudal portion began to form the crypt and the vascular plexus
      built up from a few layers was situated apart from the boundary between the
      epithelium and the mesenchyme. As the development proceeded, the formation of the
      crypt occurred in the caudorostral direction. The developing crypt advanced into
      the vascular plexus, so that a few vessels situated in the mesenchyme between
      crypts. As the crypt elongated, these vessels formed a small plexus situated
      perpendicular to the primary plexus, while the primary plexus became monolayered
      and loosened. The new plexus was composed of ascending vessels and traversing
      ones, but the regular honeycomb-like plexuses around openings of crypts have not
      established yet even in 18 days of gestation. The vascular system as well as the
      crypt in the distal colon will take further a few postnatal weeks to be
      completed.

PMID- 18085623
TI  - Bridging mucosal vessels associated with rhythmically oscillating blood flow in
      murine colitis.
AB  - Oscillatory blood flow in the microcirculation is generally considered to be the
      result of cardiopulmonary influences or active vasomotion. In this report, we
      describe rhythmically oscillating blood flow in the bridging vessels of the mouse
      colon that appeared to be independent of known biological control mechanisms.
      Corrosion casting and scanning electron microscopy of the mouse colon
      demonstrated highly branched bridging vessels that connected the submucosal
      vessels with the mucosal plexus. Because of similar morphometric characteristics
      (19 +/- 11 microm vs. 28 +/- 16 microm), bridging arterioles and venules were
      distinguished by tracking fluorescent nanoparticles through the microcirculation
      using intravital fluorescence videomicroscopy. In control mice, the blood flow
      through the bridging vessels was typically continuous and unidirectional. In
      contrast, two models of chemically induced inflammation (trinitrobenzenesulfonic
      acid and dextran sodium sulfate) were associated with a twofold reduction in flow
      velocity and the prominence of rhythmically oscillating blood flow. The blood
      oscillation was characterized by tracking the bidirectional displacement of
      fluorescent nanoparticles. Space-time plots and particle tracking of the
      oscillating segments demonstrated an oscillation frequency between 0.2 and 5.1
      cycles per second. Discrete Fourier transforms demonstrated a power spectrum
      composed of several base frequencies. These observations suggest that
      inflammation-inducible changes in blood flow patterns in the murine colon
      resulted in both reduced blood flow velocity and rhythmic oscillations within the
      bridging vessels of the mouse colon.

PMID- 18085624
TI  - Distribution and quantity of contractile tissue in postnatal development of rat
      alveolar interstitium.
AB  - Alpha-smooth muscle actin (alpha-SMA) -expressing cells are important
      participants in lung remodeling, during both normal postnatal ontogeny and after
      injury. Developmental dysregulation of these contractile cells contributes to
      bronchopulmonary dysplasia in newborns, and aberrant recapitulation in adults of
      the normal ontogeny of these cells has been speculated to underlie disease and
      repair in mature lungs. The significance of airway smooth muscle has been widely
      investigated, but contractile elements within the pulmonary parenchyma, although
      also of structural and functional consequence in developing and mature lungs, are
      relatively unstudied and little quantitative information exists. Here, we
      quantify the areal density of alpha-SMA expression in lung parenchyma and assess
      changes in its spatiotemporal distribution through postnatal ontogeny. Using an
      antibody against alpha-SMA, we immunofluorescently labeled contractile elements
      in lung sections from a postnatal growth series of rats. Images were segmented
      using thresholded pixel intensity. Alpha-SMA areal density in the alveolar
      interstitium was calculated by dividing the area of alpha-SMA-positive staining
      by the tissue area. The areal density of alpha-SMA in 2-day neonates was 3.7%,
      almost doubled, to 7.2% by 21 days, and decreased to 3% in adults. Neonates had
      large, elongate concentrations of alpha-SMA, and alpha-SMA localized both at
      septal tips and within the interstitium. In adults, individual areas of alpha-SMA
      expression were smaller and more round, and located predominately in alveolar
      ducts, at alveolar ends and bends. The results are consistent with increasing
      alpha-SMA expression during the period of peak myofibroblast activity,
      corresponding to the phase of rapid alveolarization in the developing lung.

PMID- 18085625
TI  - Effects of exogenous thyroid hormone on the postnatal morphogenesis of the rat
      parotid gland.
AB  - Administration of thyroid hormone has been shown to accelerate the early
      postnatal development of the rat parotid gland, but these studies have dwelt
      almost entirely on biochemical changes. The objective of this study was to
      describe the effects of exogenous thyroid hormone on morphologic aspects of the
      developing parotid gland, in particular the transient appearance of scattered
      mucous cells in this otherwise serous gland. Pups were given a daily subcutaneous
      injection of thyroxine (T(4)) of 0.1, 0.5, or 5.0 microg/g body weight, vehicle
      only (injection control), or no injection (normal control) beginning at 4 days,
      and killed for the collection of blood and parotid glands at intervals through 15
      days. The serum was analyzed for T(4) and the glands were examined by light and
      electron microscopy. The results indicated that both serum T(4) and the pace of
      gland development were proportional to the dose of T(4). In particular, T(4)
      accelerated decreases in acinar size and gland area occupied by stroma and
      translocation of a subset of cells with small secretory granules, deeply stained
      with periodic acid-Schiff, from acini to intercalated ducts. However, the
      chronology of mucous cell disappearance was indifferent to treatment. In
      addition, signs of toxicity, including slower gain in body weight and greatly
      increased apoptosis and vacuoles in the glands, occurred with the higher doses of
      T(4).

PMID- 18085626
TI  - Formation process and fate of the nuclear chain after injury in regenerated
      myofiber.
AB  - Although it is well known that regenerated myofibers contain nuclear chains
      (arrayed nuclear clusters), details of its process of formation and fate are
      still remained unclear. In the present study, we isolated single myofibers from
      injured ICR mouse tibialis anterior muscles by the alkali maceration-based
      method, and carried out histological observation and bromodeoxyuridine (BrdU)
      pulse-chase analysis on the nuclear chains. The nuclear chains were formed after
      injury and remained stable for at least 6 months after injury. When BrdU was
      administered during the first 4 days after injury, up to 56% of nuclei in the
      nuclear chains were labeled with BrdU, whereas when BrdU was administered 5 days
      or later after injury, less than 3% of myonuclei were labeled with BrdU. Among
      BrdU-positive nuclei in the nuclear chains, the nuclei showing attenuated and
      strong BrdU signal were dominant when BrdU was administered at the time points of
      0-2 and 3-4 days after injury, respectively. These results suggest that
      successive nuclear divisions occur during the first 4 days after injury and might
      be involved in the appearance of the stable nuclear chains in regenerated
      myofibers.

PMID- 18085627
TI  - Bone remodeling in maxilla, mandible, and femur of young dogs.
AB  - Bone remodeling in the jaw is essential for metabolic needs, mechanical demands
      and for growth of the skeleton. Currently, there is no information on remodeling
      in the jaw of young dogs. Four approximately 5-month-old male dogs were given a
      pair of calcein bone labels. After killing, bone sections were obtained from the
      maxilla, mandible, and femur. The jaw specimens were obtained from regions
      associated with erupting permanent teeth. Undecalcified specimens were prepared
      for examination by histomorphometric methods to evaluate mineral apposition rate
      (microm/d), mineralizing surface/bone surface (%), and bone formation rate (BFR,
      %/yr) in the bone supporting erupting teeth and in the femurs. Only intracortical
      secondary osteonal remodeling units were measured. There were significant (P <
      0.05) differences in the BFR for the three sites examined, with the highest BFR
      (72%/yr) being in the femur. The mandible had a BFR twofold greater than the
      maxilla (51%/yr vs. 25.5%/yr). The rate of turnover in the jaw and femur of young
      dogs is distinct from a similar comparison between the jaw and appendicular
      skeleton of adult ( approximately 1 yr old) dogs. Although BFR decreases with age
      in the femur, it remains elevated in the jaws.

PMID- 18085628
TI  - Strain-specific and endocrine control of granular convoluted tubule cells and
      epidermal growth factor expression in the mouse submandibular gland.
AB  - Submandibular glands (SMGs) of 11-week-old mice from four strains, ICR, C57BL/6J,
      BALB/c, and C3H/HeN were examined by immunohistochemistry for epidermal growth
      factor (EGF). In addition to sex-related differences in granular convoluted
      tubules (GCTs), the GCT cells were significantly larger in ICR mice than in other
      three strains. In males from each of the strains, almost all the GCT cells were
      strongly positive for EGF. The EGF-positive cells in the females, however, were
      markedly fewer in number, and were stained weaker in C57BL/6J, BALB/c, and
      C3H/HeN mice than in ICR mice. The GCT cells and their EGF expression in the F1
      progeny from ICR and C3H/HeN strains were approximately intermediate between
      those of the parent strains of the same sex. T(3) and/or dihydrotestosterone
      (DHT) enhanced the GCT phenotype in the C3H/HeN mice, and remarkably increased
      the EGF-positive cells in females. Electron microscopy revealed that gold
      labeling of EGF was confined to the secretory granules, and that the GCT cells in
      females, given T(3) + DHT, had a well-developed Golgi apparatus and net-like RER
      but few basal infoldings, whereas the equivalent cells in the untreated females
      had poor RER and prominent basal infoldings. These results suggest that the EGF
      concentration in SMGs is genetically high in ICR mice and low in other strain
      mice and that, considering the same response of GCT cells to T(3) and/or DHT
      between the high and low EGF strains, the low EGF concentrations might be partly
      caused by a lesser sensitivity of the GCT cells to thyroid hormones.

PMID- 18085629
TI  - Podocyte loss in aging OVE26 diabetic mice.
AB  - Recent studies show that podocyte nuclear density (N(V)) and numbers of renal
      podocytes per glomerulus (N) are altered in experimental and spontaneous diabetes
      mellitus. N(V) and N are generally reduced, and it has been hypothesized that
      these morphological changes may relate to the loss of glomerular permselectivity
      in diabetic nephropathy (DN). In the current study, OVE26 transgenic diabetic
      mice and age-matched (FVB) controls (60, 150, or 450 days) were fixed by vascular
      perfusion and renal cortical tissues were prepared for morphometric analyses.
      ImageJ software and point counting analyses were carried out on light and
      transmission electron micrographs to determine glomerular volume (V(G)), N(V),
      and N. As expected, mean V(G) in OVE26 mice increased substantially (
      approximately 134%) over the course of the study and was significantly increased
      over FVB mice at all ages. At 60 days, N(V) and N were not statistically
      distinguishable in OVE26 and control mice, while at 150 days, N(V) was
      significantly reduced in diabetics but not N. In 450-day-old OVE26 animals,
      however, N(V) and N were both significantly decreased ( approximately 231% and
      approximately 99%, respectively) relative to age-matched FVB mice. These data
      suggest that in the OVE26 model of diabetes, significant podocyte loss occurs
      relatively late in the course of the disease. Moreover, it seems possible that
      these podocytic changes could play a role in sustaining the increased
      permeability of the blood-urine barrier in the later stages of diabetic renal
      decompensation.

PMID- 18085630
TI  - Effect of enamel prism decussation and chemical composition on the biomechanical
      behavior of dental tissue: a theoretical approach to determine the loading
      conditions to which modern human teeth are adapted.
AB  - This theoretical study explored whether the directions of loads to which modern
      human molars are commonly subjected to are reflected in the biomechanical
      behavior of the tissue itself. A detailed finite element model of a piece of
      decussating enamel (M(3) paracone) was created, taking into account differences
      in crystal orientation between the prism head and the interprismatic matrix, and
      was tested under differently angled mediolateral loads (i.e., mimicking various
      stages of the chewing cycle). Second, although teeth are highly mineralized, they
      also contain organic material and water, while in modern humans, there are
      systematic differences in chemical composition from the outer enamel surface to
      the dentinoenamel junction. To test the biomechanical effects of this gradient in
      mineralization a second set of models with gradually changing properties was
      created and subjected to the same loads. Chemically heterogeneous enamel yielded
      overall lower stress levels than homogenous enamel, especially at extreme loading
      angles. However, the general trends regarding the increase in tensile stresses at
      more oblique angles, and the number of nodes exhibiting tension, were comparable
      between the different set-ups. The findings support suggestions that (a) the
      biomechanical behavior of dental tissue is the combined result of micromorphology
      and chemical composition and (b) that the range of loading directions, to which
      teeth are normally subjected to, can be inferred from dental microanatomy. For
      (palaeo)biological applications, the findings suggest that the absolute strength
      of teeth (e.g., bite force) cannot be predicted with certainty, whereas kinematic
      parameters of the masticatory apparatus can.

PMID- 18085631
TI  - Development of outer hair cells in Ames waltzer mice: mutation in protocadherin
      15 affects development of cuticular plate and associated structures.
AB  - The Ames waltzer (av) mouse mutant harbors a mutation in the protocadherin 15
      gene (Pcdh15) and is a model for deafness in Usher syndrome 1F and nonsyndromic
      deafness DFNB23. Mutation in Pcdh15 affects stereocilia morphogenesis and
      polarity. Disruptions of apical cellular components in outer hair cells have also
      been described in av mutants. Organization of stereocilia and cell polarization
      may be dependent on proper orientation of structural components residing in the
      apical portion of the cell during development. We used electron and
      immunofluorescent microscopy to examine structural maturation of outer hair cells
      in av3J mice with emphasis on the fonticulus, basal body/centriole complex, actin
      mesh, and the microtubule network during initiation of bundle organization,
      between embryonic day (E) 16.5 and postnatal day 5 (P5). We found major
      ultrastructural rearrangements near the hair cell surface in av3J mice. Earliest
      changes were in kinocilia, basal body, and stereocilia positioning and
      microtubule arrangement once the kinocilia had lateralized to the side of the
      cell (between E16.5 and postnatal day [P] 0, before cuticular plate formation and
      stereocilia elongation). By P0, the developing fonticulus in av mice appeared
      enlarged, with a normal vesicle density. Stereocilia bundle disorganization
      increased after P0, with disruptions of the actin mesh within the cuticular
      plate. These observations support the hypothesis that mutations in Pcdh15 in av3J
      mice adversely affect coordinated maturation of apical cell components, resulting
      in disturbed stereocilia bundle polarity in av mice.

PMID- 18085632
TI  - Involvement of the klotho protein in dentin formation and mineralization.
AB  - Klotho-deficient mice exhibit multiple pathological conditions resembling human
      aging. Our previous study showed alterations in the distribution of osteocytes
      and in the bone matrix synthesis in klotho-deficient mice. Although the bone and
      tooth share morphological features such as mineralization processes and
      components of the extracellular matrix, little information is available on how
      klotho deletion influences tooth formation. The present study aimed to elucidate
      the altered histology of incisors of klotho-deficient mice-comparing the findings
      with those from their wild-type littermates, by using immunohistochemistry for
      alkaline phosphatase (ALP), osteopontin, and dentin matrix protein-1 (DMP-1),
      terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end
      labeling (TUNEL) detection for apoptosis, and electron probe microanalyzer (EPMA)
      analysis on calcium (Ca), phosphate (P), and magnesium (Mg). Klotho-deficient
      incisors exhibited disturbed layers of odontoblasts, predentin, and dentin,
      resulting in an obscure dentin-predentinal border at the labial region. Several
      odontoblast-like cells without ALP activity were embedded in the labial dentin
      matrix, and immunopositivity for DMP-1 and osteopontin was discernible in the
      matrix surrounding these embedded odontoblast-like cells. TUNEL detection
      demonstrated an apoptotic reaction in the embedded odontoblast-like cells and
      pulpal cells in the klotho-deficient mice. EPMA revealed lower concentrations of
      Ca, P, and Mg in the klotho-deficient dentin, except for the dentin around
      abnormal odontoblast-like cells. These findings suggest the involvement of the
      klotho gene in dentinogenesis and its mineralization.

PMID- 18085633
TI  - Effectiveness of the Thin Prep Imaging System in the detection of adenocarcinoma
      of the gynecologic system.
AB  - BACKGROUND: The ThinPrep Imaging System (TIS) has been approved by the U.S. Food
      and Drug Administration for use to decrease the number of false-negative results
      in ThinPrep (TP) gynecologic specimens and increase cytotechnology productivity.
      Although the increased detection of squamous abnormalities using the TIS has been
      well documented, to the authors' knowledge, data regarding the impact of the TIS
      in the detection of glandular abnormalities is limited. The goal of the current
      study was to evaluate the effectiveness of the TIS in detecting glandular
      abnormalities in cervicovaginal specimens. METHODS: TIS evaluated TP tests with
      histologic confirmation of adenocarcinoma involving the gynecologic system were
      included in the current study. Two cytotechnologists independently reviewed the
      cases for the presence or absence of atypical glandular cells. Review results
      were correlated with initial cytologic and histologic diagnoses. RESULTS: A total
      of 124 cases met the criteria for inclusion in the current study. Seventy of
      these cases (56%) were found to contain atypical glandular cells on the TP slide.
      TIS was able to identify atypical cells in 97% of these cases (68 of 70 cases).
      Nine cases initially reported as benign were found to contain atypical glandular
      cells on secondary review. All but 1 of these cases contained atypical glandular
      cells detected by the TIS. The majority of these false-negative cases (6 of 9
      cases) derived from endometrial adenocarcinoma. No cytologic evidence of a
      glandular abnormality was found in the 54 remaining cases. CONCLUSIONS: The TIS
      was found to be effective in identifying atypical glandular cells in specimens
      containing malignant glandular cells, leading to a full review of the slide.

PMID- 18085634
TI  - Nodule heterogeneity as shown by size differences between the targeted nodule and
      the tumor in thyroidectomy specimen: a cause for a false-negative diagnosis of
      papillary thyroid carcinoma on fine-needle aspiration.
AB  - BACKGROUND: Missed papillary thyroid carcinoma (PTC) diagnoses on fine-needle
      aspiration (FNA) can result from many causes. To the authors' knowledge, the
      issue of whether the detection of PTC is correlated with nodule heterogeneity has
      not been studied to date. METHODS: The authors identified all thyroidectomy
      specimens with a diagnosis of PTC that had undergone at least 1 prior FNA in the
      study institution between 1998 and 2003. The tumor size at the time of the
      resection, the ultrasound (US)-determined nodule size, and other parameters were
      compared between the 2 groups in which PTC was or was not diagnosed on FNA.
      RESULTS: Of a total of 89 specimens, 47 were diagnosed on FNA with an average
      tumor size of 1.7 cm and an US-determined nodule size of 2.1 cm (a difference of
      0.4 cm). Forty-two specimens with a smaller average tumor size of 0.9 cm (P <
      .0001) and a US-determined nodule size of 2.4 cm (a difference of 1.5 cm) were
      missed. The differences with regard to the US-determined nodule size and tumor
      size between the 2 groups were significant (0.4 cm vs 1.5 cm; P < .0001). In the
      missed group, 29 specimens were found to have PTC foci that measured < or = 1.0
      cm and 26 had a reasonable size difference (RSD; defined as a PTC size outside
      the range of +/-50% of the US-determined nodule size) as the indicator of the
      mixed nature of nodules targeted for FNA, whereas in the diagnostic group, 9 foci
      measured < or = 1.0 cm and 6 had RSD. There was no cytologic evidence with which
      to render a diagnosis of PTC on further review in the missed group. CONCLUSIONS:
      The major reason for a missed diagnosis of PTC on FNA is because of inadequate
      tumor sampling due to the heterogeneity of the nodule targeted for FNA. This is
      illustrated by the RSD noted between the targeted nodule and the actual PTC tumor
      focus in the resection specimen.

PMID- 18085635
TI  - Connexin 43 expression delineates two discrete pathways in the human
      atrioventricular junction.
AB  - Gap junction expression has been studied in the atrioventricular junction (AVJ)
      of many species, however, their distribution in the human AVJ is unknown. The AVJ
      expression of the gap junction protein connexin 43 (Cx43) is species dependent;
      therefore we investigated its distribution in the human AVJ. Using Masson
      trichrome histology, we reconstructed the AVJ of three normal human hearts and
      one with dilated cardiomyopathy in three dimensions. Cx43 was immunolabeled with
      vimentin and alpha-actinin to determine the cellular origin of Cx43 and was
      quantified in the following structures: interatrial septum (IAS), His bundle,
      compact node (CN), lower nodal bundle (LNB), leftward and rightward nodal
      extensions (LE and RE), and inferior, endocardial, and left-sided transitional
      cells. Histology revealed two nodal extensions in three of four hearts. Cx43 was
      found in the myocytes, but not fibroblasts, of the AVJ. LE and CN Cx43 was lower
      than the IAS (P < 0.05) and the RE, LNB, and His all expressed Cx43 similarly,
      with approximately half of IAS expression (RE: 44 +/- 36%; LNB: 50 +/- 26%; His:
      48 +/- 12%, P = NS compared with IAS). Cx43 levels in transitional cells were
      similar to the IAS (P = not significant). Cx43 was found in myocytes of the human
      AVJ, and its expression pattern delineates two separate continuous structures:
      one consists of the LE and CN with little Cx43, and the other consists of the
      His, LNB, and RE expressing approximately half the Cx43 of the IAS. The
      differential Cx43 expression may provide each structure with unique conduction
      properties, contributing to arrhythmias arising from the AVJ.

PMID- 18085636
TI  - Fine-needle aspiration of follicular adenoma versus parathyroid adenoma: the
      utility of multispectral imaging in differentiating lesions with subtle
      cytomorphologic differences.
AB  - BACKGROUND: Multispectral image analysis is an emerging tool that utilizes both
      spatial and spectral image information to classify images that can be used for
      the differentiation between benign versus malignant cells. The aim of the current
      study was to analyze the ability of this tool in differentiating subtle cytologic
      differences that cannot be appreciated by the human eye. Herein, the authors used
      fine-needle aspirations (FNAs) of follicular adenoma (FA) and parathyroid adenoma
      (PA) as a test case. METHODS: The Nuance platform was used to collect image
      stacks that were subsequently analyzed with CRI-MLS software, a neural network
      based artificial intelligence system that can classify images using automatically
      "learned" spatial-spectral features. CRI-MLS was trained on random, well
      preserved FA cells and PA cells from the training set (n = 45 cells each). An
      algorithmic solution was developed and then validated on an independent series
      comprised of 1904 FA cells from 5 FA cases and 690 PA cells from 5 PA cases.
      RESULTS: The solution from the CRI-MLS classifier showed 1876 FA cells (98.5%) as
      true FA and 28 FA cells (1.5%) as false PA, whereas 663 PA cells (96%) were true
      PA and 27 PA cells (4%) were false FA. The summary result of this solution was a
      sensitivity of 98.5%, a specificity of 96.1%, and a positive predictive value of
      98.6%. CONCLUSIONS: The best spatial-spectral imaging solution was able to
      correctly classify 2534 of 2594 cells (98%) and misclassified only 55 of 2594
      cells (2%). These data suggest that this technology may be valuable in a clinical
      setting to help differentiate and classify morphologically similar lesions.

PMID- 18085637
TI  - The helix-loop-helix protein Id2 is expressed differentially and induced by myc
      in T-cell lymphomas.
AB  - BACKGROUND: Inhibitor of DNA binding 2 (Id2), a helix-loop-helix protein of the
      inhibitor of differentiation (ID) family, is involved in hematopoiesis, mainly
      through interaction with the E-family of transcription factors. Recent studies
      have shown that Id2 is overexpressed in some types of B-cell lymphoma, including
      classical Hodgkin lymphoma. The authors of the current study hypothesized that
      Id2 also is overexpressed in T-cell lymphomas. METHODS: By using reverse
      transcriptase polymerase chain reaction (RT-PCR) and Western blot analyses, high
      Id2 messenger RNA (mRNA) and protein levels, respectively, were detected in all 4
      T-cell anaplastic large cell lymphoma (ALCL) cell lines that were tested.
      RESULTS: Immunohistochemistry results indicated that Id2 was expressed strongly
      in 21 of 27 (78%) ALCL tumors (79% anaplastic lymphoma kinase [ALK]-negative and
      75% ALK-positive), in 5 of 10 (50%) extranodal natural killer/T (NK/T)-cell
      lymphomas of the nasal type, in 2 of 8 (25%) cutaneous ALCLs, in 2 of 9 (22%)
      enteropathy type T-cell lymphomas, in 1 of 5 (20%) peripheral T-cell lymphomas
      not otherwise specified, and in 1 of 8 (13%) T-cell prolymphocytic leukemias.
      Other types of T-cell lymphoma were negative for Id2. Because it is known that
      myc is expressed in ALCL, myc was inhibited selectively in 2 ALCL cell lines,
      resulting in a concentration-dependent decrease in Id2 mRNA and protein levels.
      Conversely, forced expression of myc in HEK 293T cells using an myc/green
      fluorescent protein adenoviral vector resulted in Id2 up-regulation. CONCLUSIONS:
      Taken together, the current data suggest that Id2 commonly is overexpressed in
      highly proliferative T-cell lymphomas, and its expression may result from
      transcriptional activation of myc in these tumors.

PMID- 18085638
TI  - Prognostic value of immunophenotyping in elderly patients with acute myeloid
      leukemia: a single-institution experience.
AB  - BACKGROUND: The poor prognosis for elderly patients with acute myeloid leukemia
      (AML) raises questions regarding the benefit of treating them with intensive
      chemotherapy. The impact of initial characteristics on prognosis has been
      addressed previously in elderly patients; however, very few data are available
      regarding the prognostic value of immunophenotypic characteristics in this
      setting. METHODS: The authors investigated expression of the membrane antigens
      CD13, CD15, CD33, and CD34 by flow cytometry in elderly patients with newly
      diagnosed AML and analyzed whether these parameters had clinical or prognostic
      relevance to help physicians in their choice of therapy. RESULTS:
      Immunophenotyping was performed in 273 patients aged > or =60 years (median age,
      69 years). CD13 was expressed in 73% of patients, CD15 was expressed in 43% of
      patients, CD33 was expressed in 64% of patients, and CD34 was expressed in 66% of
      patients. Complete remission was obtained in 157 patients (58%). The median
      overall survival was 8.1 months, and the 3-year survival rate was 14%. Three risk
      groups were defined based on CD34 and CD33 antigen expression: The poor-risk
      group included patients with CD34-positive/CD33-positive or CD34-negative/CD33
      negative disease, the intermediate-risk group included patients with CD34
      positive/CD33-negative disease, and the favorable-risk group included patients
      with CD34-negative/CD33-positive disease. After cytogenetic analyses,
      immunophenotype was the most significant prognostic factor in terms of survival
      in a multivariate analysis (P = .03 and P < .0001, respectively). When
      immunophenotypic and cytogenetic parameters were combined, patients were
      classified into 4 prognostic groups: Group A (3-year survival rate, 33%) included
      patients with favorable and normal karyotypes who had a favorable
      immunophenotype, Group B (3-year survival rte, 28%) included patients with normal
      karyotypes who had an intermediate immunophenotype, Group C (3-year survival
      rate, 8%) included patients with intermediate or normal karyotypes who had an
      unfavorable immunophenotype, and Group D (3-year survival rate, 2%) included all
      patients who had unfavorable cytogenetics. CONCLUSIONS: Immunophenotypic
      characteristics appeared to be a major prognostic factor in this population of
      elderly patients with AML. By using 2 simple parameters assessed at the time of
      diagnosis, the authors devised a prognostic system of immediate clinical utility
      for prognostic stratification and risk-adapted therapeutic choices.

PMID- 18085640
TI  - Adopting health behavior change theory throughout the clinical practice guideline
      process.
AB  - Adopting a theoretical framework throughout the clinical practice guideline (CPG)
      process (development, dissemination, implementation, and evaluation) can be
      useful in systematically identifying, addressing, and explaining behavioral
      influences impacting CPG uptake and effectiveness. This article argues that using
      a theoretical framework should increase the utility and probably the
      implementation of a CPG. A hypothetical scenario is provided using the theory of
      planned behavior (TPB) to aid in our explanation. While other theories may be
      viable, the TPB is chosen because it accounts for a wide spectrum of behavioral
      factors known to influence physician behavior, and because its flexibility allows
      it to be used for different populations (e.g., specialists), behaviors, and
      contexts (e.g., hospital, private clinic). In addition, evidence has indicated
      that the TPB can influence physician behavior. Empirical research examining
      whether CPG utility can be significantly improved by appropriately selecting and
      implementing theory throughout the CPG process is warranted.

PMID- 18085639
TI  - Identification of serum biomarkers for nasopharyngeal carcinoma by proteomic
      analysis.
AB  - BACKGROUND: Early diagnosis of nasopharyngeal carcinoma (NPC) remains a
      challenge. Serum protein profiling is a promising approach for the classification
      of cancer versus noncancer samples. The objective of the current study was to
      assess the feasibility of mass spectrometry-based protein profiling and a
      classification tree algorithm for discriminating between patients with NPC and
      noncancer controls. METHODS: Serum samples from patients with NPC and noncancer
      controls were analyzed by using surface-enhanced laser desorption/ionization time
      of-flight mass spectrometry (SELDI-TOF-MS). The study was divided into a
      preliminary training set and a blind test set: A preliminary training set and a
      classification tree of spectra derived from 55 patients with NPC and a group of
      60 noncancer controls were used to develop a proteomic model that discriminated
      cancer from noncancer effectively. Then, the validity of the classification tree
      was challenged with a blind test set, which included another 25 patients with NPC
      and 28 noncancer controls. RESULTS: Four protein peaks at 4097 daltons (Da), 4180
      Da, 5912 Da, and 8295 Da were chosen automatically as a biomarker pattern in the
      training set that discriminated cancer from noncancer with sensitivity of 94.5%
      and specificity of 96.7%. When the SELDI marker pattern was tested with the
      blinded test set, it yielded a sensitivity of 92%, a specificity of 92.9%, and an
      accuracy rate of 92.5%. The accuracy of 2 protein peaks (4581 Da and 7802 Da) was
      80% for predicting stage I and II NPC and 86% for predicting stage III and IV
      NPC. CONCLUSIONS: The high sensitivity and specificity obtained by the serum
      protein profiling approach demonstrated that SELDI-TOF-MS combined with a tree
      analysis model both can facilitate discriminating between NPC and noncancer
      controls and can provide an innovative clinical diagnostic platform to improve
      the detection of NPC.

PMID- 18085641
TI  - Step-by-step: a model for practice-based learning.
AB  - INTRODUCTION: Innovative technology has led to high-precision radiation therapy
      that has dramatically altered the practice of radiation oncology. This
      qualitative study explored the implementation of this innovation into practice
      from the perspective of the practitioners in a large academic radiation medicine
      program and aimed to improve understanding of and facilitate the educational
      process of this change. METHODS: Multiprofession staff participated in a series
      of seven focus groups and nine in-depth interviews, and the descriptive data from
      the transcripts were analyzed using grounded theory methodology. RESULTS:
      Practitioners believed that there had been a major effect on many aspects of
      their practice. The team structure supported the adoption of change. The
      technology changed the way the practices worked. Learning new skills increased
      workload and stress but led to a new conception of the discipline and the
      generation of new practice-based knowledge. When the concepts were examined
      longitudinally, a four-step process of learning was identified. In step 1, there
      was anxiety as staff acquired the skills to use the technology. Step 2 involved
      learning to interpret new findings and images, experiencing uncertainty until new
      perspectives developed. Step 3 involved questioning assumptions and critical
      reflection, which resulted in new understanding. The final step 4 identified a
      process of constructing new knowledge through research, development, and dialogue
      within the profession. DISCUSSION: These findings expand our understanding of how
      practice-based learning occurs in the context of change and can guide learning
      activities appropriate to each stage.

PMID- 18085642
TI  - Economic stress among low-income women with cancer: effects on quality of life.
AB  - BACKGROUND: Attention to the economic consequences of cancer has grown as the
      number of cancer survivors is increasing. Although prevalent among low-income
      minority survivors, the impact of economic stress on quality of life (QOL)
      remains largely unexplored. METHODS: Data are reported for 487 predominantly
      Hispanic low-income women with a primary diagnosis of breast or gynecological
      cancer and undergoing active treatment or follow-up. Cross-sectional and
      longitudinal analyses examined the effects of economic concerns on QOL,
      depression, and anxiety. RESULTS: Rates of unemployment, medical cost and wage
      concerns, and financial stress were high in this study population, at baseline,
      respectively, 70%, 68%, 47%, and 49%. The proportions reporting unemployed status
      and medical cost concerns stayed flat from baseline to 6 months, followed by a
      pronounced drop at 12 months. Patient reported rates of lost wage worries
      increased from baseline to 6 months, followed by a moderate decrease. Functional,
      emotional, physical, and social-family well-being and depression and anxiety
      scores exhibited consistent linear improvement from baseline to 12 months. Over
      12 months, patients reporting economic concerns had significantly poorer
      functional, emotional, and affective well-being. CONCLUSIONS: Economic stress is
      negatively associated with QOL, highlighting the importance of addressing
      economic stress in low-income women with cancer.

PMID- 18085643
TI  - A rough morphology of the adsorbed fibronectin layer favors adhesion of neuronal
      cells.
AB  - A range of substrates made of polystyrene (PS) and poly(methyl methacrylate)
      poly(methacrylic acid) copolymer (PMMA-PMAA) containing 98 and 80% PMMA (PA98,
      PA80) and presenting a homogeneous or a patterned surface were used to study
      fibronectin adsorption and neuronal cell behavior. Fibronectin adsorption showed
      weak differences regarding the adsorbed amount (evaluated by XPS), but large
      differences in adsorbed layer morphology as observed by AFM. A fine granular
      morphology, with dimensions up to 8 nm height and 50-150 nm width, was observed
      on top of a thin adsorbed layer in the case of PS, PA98, and of a surface made of
      nanoscale inclusions of the latter in PS. In contrast, the layer adsorbed on
      PA80, which carries more ionizable groups, showed a higher roughness on the PA80
      zones with differences in height up to 30 nm and characteristic lateral
      dimensions of 400 nm. On substrates of the former category, the cells formed
      large clusters, revealing poor interactions with the substrate. On PA80, the
      cells formed large networks with only a few small clusters. The adsorbed layer
      roughness, resulting from aggregation of fibronectin upon adsorption and from the
      substrate surface chemical composition, is responsible for neuronal cell
      spreading and growth. Its effect is not prevented by the presence of inclusions
      (< 30% of the surface) responsible for smoother areas of adsorbed fibronectin and
      for protrusions below 40 nm.

PMID- 18085644
TI  - The artificial surface-induced whole blood inflammatory reaction revealed by
      increases in a series of chemokines and growth factors is largely complement
      dependent.
AB  - Exposing blood to an artificial surface results in a systemic inflammatory
      response, including cytokine release and complement activation. We studied the
      artificial surface-induced inflammation in human whole blood using an extensive
      panel of inflammatory mediators including proinflammatory cytokines, chemokines
      and growth-factors and investigated the role of the complement system in the
      induction of this response. Using multiplex technology, 27 different inflammatory
      mediators were measured after circulating blood for 4 hours in polyvinyl chloride
      tubing. The C3 inhibitor compstatin was used to block complement activation. A
      significant (p < 0.05) increase in 14 of the 27 mediators was induced by the
      surface, of which 7 were chemokines (IL-8, MCP-1, MIP-1alpha, MIP-1beta, RANTES,
      eotaxin and IP-10) and 5 were growth-factors (G-CSF, GM-CSF, VEGF, PDGF and FGF).
      The traditional proinflammatory cytokines like IL-1beta, TNFalpha and IL-6 were
      not induced, although IL-6, as well as IL-15 and IL-17 increased if the surface
      was coated with highly bioincompatible laminaran. Inhibition of complement
      activation with compstatin significantly (p < 0.05) reduced the formation of 12
      of the 14 mediators. For 10 of the 12 mediators, the inhibition was by 2/3 or
      more, for the remaining two the inhibition was more moderate. A highly
      biocompatible heparin-coated PVC surface was used as negative control and
      completely abolished the whole inflammatory response. The artificial surface PVC
      markedly induced a broad spectrum of chemokines and growth-factors, which was
      largely dependent on activation of complement.

PMID- 18085645
TI  - Synthetic zeolites as a new tool for drug delivery.
AB  - Synthetic zeolites were studied in order to investigate their ability to
      encapsulate and to release drugs. In particular, a zeolite X and a zeolitic
      product obtained from a cocrystallization of zeolite X and zeolite A were
      examined. These materials were characterized by chemical analyses (ICP-AES), X
      ray diffraction, nitrogen adsorption isotherm, scanning electron microscopy,
      laser diffraction, and infrared spectroscopy. Since ketoprofen was chosen as a
      model drug for the formulation of controlled-release dosage forms, it was
      encapsulated into these two types of synthetic zeolites by a soaking procedure.
      Drug-loaded matrices were then characterized for entrapped drug amount and
      thermogravimetric behavior. In both types of activated zeolites, the total amount
      of ketoprofen (800 mg) was encapsulated in 2 g of matrix. By using HPLC
      measurements, ketoprofen release studies were done at different pH conditions so
      as to mimick gastrointestinal fluids. The absence of release in acid conditions
      and a double phased release, at two different pH values (5 and 6.8), suggest that
      after activation these materials offer good potential for a modified release
      delivery system of ketoprofen.

PMID- 18085646
TI  - The relationship between femoral periprosthetic cortical bone geometry and
      porosity after total hip arthroplasty.
AB  - Stress shielding from the presence of a femoral component can cause adverse
      changes to cortical bone geometry and porosity leading to increased fracture risk
      in the periprosthetic cortical bone. The objectives of this study were to
      determine if porosity increased after total hip arthroplasty along the principal
      axes, and to determine if a relationship existed between cortical bone porosity
      and geometry. Ten postmortem donors allowed comparisons of implanted femurs to
      the contralateral nonimplanted femurs. Transverse cross-sections of the femur
      were taken at 25, 45, 65, and 85% along the length of the femoral component. The
      cortical bone principal axes' location (degrees) and rigidity values (mm(4)) were
      based on cortical bone geometry by using digitized images of the cortical bone
      cross-sections. Percent porosity was measured along the principal axes using
      backscatter electron imaging. Cortical bone porosity increased in the more distal
      sections of the implanted femurs by approximately 3%, but did not preferentially
      increase along a particular principal axis. No correlation was found between
      changes in porosity and rigidity values. In conclusion, the porosity increases in
      the implanted femurs may have regionally reduced cortical bone strength. The
      locations of higher porosity did not appear related to the cortical bone
      geometry.

PMID- 18085647
TI  - Biocompatibility of atomic layer-deposited alumina thin films.
AB  - Presented in this paper is a study of the biocompatibility of an atomic layer
      deposited (ALD) alumina (Al2O3) thin film and an ALD hydrophobic coating on
      standard glass cover slips. The pure ALD alumina coating exhibited a water
      contact angle of 55 degrees +/- 5 degrees attributed, in part, to a high
      concentration of -OH groups on the surface. In contrast, the hydrophobic coating
      (tridecafluoro-1,1,2,2-tetrahydro-octyl-methyl-bis(dimethylamino)silane) had a
      water contact angle of 108 degrees +/- 2 degrees. Observations using differential
      interference contrast microscopy on human coronary artery smooth muscle cells
      showed normal cell proliferation on both the ALD alumina and hydrophobic coatings
      when compared to cells grown on control substrates. These observations suggested
      good biocompatibility over a period of 7 days in vitro. Using a colorimetric
      assay technique to assess cell viability, the cellular response between the three
      substrates can be differentiated to show that the ALD alumina coating is more
      biocompatible and that the hydrophobic coating is less biocompatible when
      compared to the control. These results suggest that patterning a substrate with
      hydrophilic and hydrophobic groups can control cell growth. This patterning can
      further enhance the known advantages of ALD alumina, such as conformality and
      excellent dielectric properties for bio-micro electro mechanical systems (Bio
      MEMS) in sensors, actuators, and microfluidics devices.

PMID- 18085648
TI  - Nanopatterning of fibronectin and the influence of integrin clustering on
      endothelial cell spreading and proliferation.
AB  - Investigating stages of maturation of cellular adhesions to the extracellular
      matrix from the initial binding events to the formation of small focal complexes
      has been challenging because of the difficulty in fabricating the necessary
      nanopatterned substrates with controlled biochemical functionality. We present
      the fabrication and characterization of surfaces presenting fibronectin
      nanopatterns of controlled size and pitch that provide well-defined cellular
      adhesion sites against a nonadhesive polyethylene glycol background. The
      nanopatterned surfaces allow us to control the number of fibronectin proteins
      within each adhesion site from 9 to 250, thereby limiting the number of integrins
      involved in each cell-substrate adhesion. We demonstrate the presence of
      fibronectin on the nanoislands, while no protein was observed on the passivated
      background. We show that the cell adheres to the nanopatterns with adhesions that
      are much smaller and more evenly distributed than on a glass control. The
      nanopattern influences cellular proliferation only at longer times, but
      influences spreading at both early and later times, indicating adhesion size and
      adhesion density play a role in controlling cell adhesion and signaling. However,
      the overall density of fibronectin on all patterns is far lower than on
      homogeneously coated control surfaces, showing that the local density of adhesion
      ligands, not the average density, is the important parameter for cell
      proliferation and spreading.

PMID- 18085649
TI  - Nanocrystalline diamond: In vitro biocompatibility assessment by MG63 and human
      bone marrow cells cultures.
AB  - Nanocrystalline diamond (NCD) has a great potential for prosthetic implants
      coating. Nevertheless, its biocompatibility still has to be better understood. To
      do so, we employed several materials characterization techniques (SEM, AFM, micro
      Raman spectroscopy) and cell culture assays using MG63 osteoblast-like and human
      bone marrow cells. Biochemical routines (MTT assays, Lowry's method, ALP
      activity) supported by SEM and confocal microscopy characterization were carried
      out. We used silicon nitride (Si3N4) substrates for NCD coatings based on a
      previous demonstration of the superior adhesion and tribological performance of
      these NCD coated ceramics. Results demonstrate an improved human osteoblast
      proliferation and the stimulation of differentiated markers, like ALP activity
      and matrix mineralization, compared with standard polystyrene tissue culture
      plates. The nanometric featuring of NCD, associated to its chemical affinity are
      key points for bone regeneration purposes.

PMID- 18085650
TI  - Targeted folic acid-PEG nanoparticles for noninvasive imaging of folate receptor
      by MRI.
AB  - The surface of superparamagnetic iron oxide nanoparticles (SPIO) with different
      molecular weight of poly(ethylene glycol) (PEG) and folic acid (FA) were
      synthesized. The SPIO-PEG-FA nanoparticles are well-dispersed and have good
      stability in various pH solutions. The lack of hysterestis and remanence at
      ambient temperatures is characteristic of superparamagnetic materials for SPIO
      PEG-FA. The uptake by macrophage for SPIO-PEG-FA is lower than that of Feridex
      I.V. even at higher concentration. Internalization of SPIO-PEG-FA in targeted
      cells (KB cells) was observed by flow-cytometric analysis and in vitro MR
      imaging. The intensity change of positive KB cell tumor (-20 to 25%) is
      significantly lower than that of negative HT-1080 cell tumor from precontrast to
      postcontrast images of the tumor by in vivo MR imaging. These preliminary results
      demonstrated that SPIO-PEG-FA have the ability to target folate receptor.

PMID- 18085651
TI  - A novel porous collagen scaffold around an implantable biosensor for improving
      biocompatibility. I. In vitro/in vivo stability of the scaffold and in vitro
      sensitivity of the glucose sensor with scaffold.
AB  - A new 3D porous and biostable collagen scaffold has been developed to improve the
      biocompatibility of implantable glucose sensors by minimizing tissue reactions
      while stimulating angiogenesis around the sensors. The novel collagen scaffold
      was crosslinked using nordihydroguaiaretic acid (NDGA) to enhance biostability.
      NDGA-treated collagen scaffolds were stable without physical deformation in the
      subcutaneous tissue of rats for 4 weeks. In contrast, glutaraldehyde (GA)-treated
      collagen scaffolds were extremely damaged following implantation. Both types of
      scaffolds (NDGA- and GA-crosslinked) were stable in vitro in the presence of
      collagenase with 70% retention of original weight after 4 weeks of incubation.
      The response current (i.e. sensitivity) of sensors with porous scaffolds was not
      significantly changed when compared with control sensors (no scaffold), while the
      response time (T(95%)) was slightly delayed after a glucose concentration
      increase from 5 to 15 mM. Above this range, the sensors coated with scaffolds had
      only a slightly lower sensitivity than the control sensors. These results
      indicate that we have developed a stable NDGA-crosslinked collagen scaffold for
      biosensors, and that the scaffold does not impair the function of our sensor. We
      plan to use this scaffold to enhance the function and lifetime of the implantable
      biosensors by providing a controlled local environment around the sensors with
      the help of various drugs and growth factors (dexamethasone, VEGF, PDGF).

PMID- 18085652
TI  - Micromechanical properties of human trabecular bone: a hierarchical investigation
      using nanoindentation.
AB  - The ability to assess the risk of fracture, evaluate new therapies, predict
      implant success and assess the influence of bone remodeling disorders requires
      specific measurement of local bone micromechanical properties. Nanoindentation is
      an established tool for assessing the micromechanical properties of hard
      biological tissues. In this study, elastic modulus and hardness were quantified
      using nanoindentation for human trabecular bone from the intertrochanteric region
      of the proximal femur. These properties were demonstrated to be heterogeneous and
      highly correlated at the intraspicule, interspicule, and interspecimen levels.
      The results of this study have important implications for current understanding
      of structure-function relationships throughout the trabecular bone structural
      hierarchy.

PMID- 18085653
TI  - Evaluation of bone healing with eggshell-derived bone graft substitutes in rat
      calvaria: a pilot study.
AB  - The purpose of this study was to investigate the potential effectiveness of a
      surface-modified natural calcium carbonate, hen eggshell (ES) as a bone graft
      substitute. The surface characteristics, cell viability on, and osteoconductivity
      of, particulated ES with and without hydrothermal treatment in phosphate
      solutions were evaluated. Hydrothermal treatment partially converted ES to
      calcium-deficient hydroxyapatite (HA) with surface microstructure. MTT assay
      indicated higher osteoblast viability on surface-modified ES compared with a
      commercially available bone substitute, anorganic bovine bone (Bio-Oss, BO) (p <
      0.001). Histological and histomorphometric analysis showed significantly greater
      new bone formation and mineralized bone-to-graft contact of surface-modified ES,
      especially with hydrothermally treated ES, compared with BO in 5-mm diameter
      calvarial defects in rats at 4 and 8 weeks of healing (p < 0.01). Complete bony
      bridging was more frequently found with hydrothermally treated ES. The results of
      this pilot study indicate the potential efficacy of surface-modified particulated
      hen eggshell as an osteoconductive bone substitute in a rat calvarial defect
      model.

PMID- 18085654
TI  - Biomimetic fabrication of fibrin/apatite composite material.
AB  - Bidirectional diffusion of the Ca and PO4 solutions into the fibrin gel was
      performed at various pH conditions and fluoride concentrations to generate
      organic/inorganic composite materials mimicking biomineralization. The minerals
      produced in this system had a higher crystallinity than those generated by the
      solution mineralization system. The minerals generated in fibrin gel varied
      depending on the pH conditions as follows: Dicalcium phosphate dihydrate (DCPD)
      in the noncontrolled pH solution, the DCPD and octacalcium phosphate (OCP)
      mixture at pH 7.4, and the OCP and hydroxyapatite (HAp) mixture at pH 9.0. When
      fluoride ions were added in the range of 2-500 ppm, the minerals produced at pH
      7.4 altered from OCP/HAp to HAp/fluorapatite (FAp). In addition, the
      crystallinity of the obtained minerals increased with an increase in fluoride ion
      concentration, and the solubility was inversely correlated to crystallinity. In
      conclusion, we established a novel fabrication method for synthesizing
      organic/inorganic composite materials composed of fibrin and calcium phosphate
      and revealed that the characteristics of the minerals in the synthesized material
      can be controlled by the fabrication condition.

PMID- 18085655
TI  - Enhanced cytotoxicity of saporin by polyamidoamine dendrimer conjugation and
      photochemical internalization.
AB  - Because of the lack of membrane binding subunit, type I ribosome-inactivating
      proteins (RIPs) are not very toxic to cells unless action is taken to allow for
      toxin internalization to the cytosol. To overcome the potential barriers that
      greatly hinder the cellular uptake and intracellular release of saporin, a type I
      RIP, we used generation 4 polyamidoamine (PAMAM) dendrimer as the carrier to
      improve its endocytic uptake, passive tumor targeting, and implemented the
      photochemical internalization (PCI) technology to facilitate its cytosolic
      release. Our results showed that the cellular uptake of saporin was increased
      after conjugation with the PAMAM dendrimer and the cytotoxic effect was improved
      by more than 1 order of magnitude. The cytotoxicity of free saporin and PAMAM
      saporin was further enhanced by the PCI technology. PCI changed the mechanism of
      cellular uptake of free saporin and then caused more saporin entering into the
      cells. After the PCI treatment, PAMAM-saporin was not only internalized into the
      cytosol but also efficiently entered the nuclei. Our results indicated that
      conjugating to PAMAM dendrimer is a possible approach to enhance the cellular
      uptake of saporin. PCI is a promising technology to significantly enhance the
      cytotoxicity of both free saporin and PAMAM-saporin. Combining both polymer
      conjugation and PCI approaches may improve the efficacy of RIPs in cancer
      therapy.

PMID- 18085656
TI  - Greater osteoblast long-term functions on ionic plasma deposited nanostructured
      orthopedic implant coatings.
AB  - Bioactive coatings are in high demand to increase the functions of cells for
      numerous medical devices. The objective of this in vitro study was to
      characterize for the first time osteoblast (bone-forming cell) long-term
      functions (such as proliferation and deposition of calcium containing mineral) on
      several potential orthopedic implant polymeric materials [specifically, ultrahigh
      molecular weight polyethylene (UHMWPE) and polytetrafluoroethylene (PTFE)] coated
      with nanostructured titanium using a novel ionic plasma deposition (IPD) coating
      process. UHMWPE is a widely used polymer in total knee and hip replacements,
      while PTFE is not, but it has been used in other orthopedic applications. The IPD
      coating process creates a surface-engineered nanostructure (with features usually
      below 100 nm) by first using a vacuum to remove all contaminants, and then
      guiding charged metallic ions or plasma to the surface of a medical device at
      ambient temperature. Results demonstrated that compared to currently used
      titanium and uncoated polymers, polymers coated with titanium using IPD
      significantly increased osteoblast proliferation and, most importantly, calcium
      deposition. In this manner, this study strongly suggests that IPD should be
      further studied for creating nanometer titanium surface feature coatings to
      enhance osteoblast functions necessary to increase orthopedic implant efficacy.

PMID- 18085657
TI  - Biological and antibacterial properties of plasma sprayed wollastonite coatings
      grafting gentamicin loaded collagen.
AB  - In this work, gentamicin loaded collagen was grafted on the surface of plasma
      sprayed wollastonite coatings to obtain an implant having excellent bioactivity
      and cytocompatibility as well as antibacterial property. The bioactivity and
      cytocompatibility of the wollastonite coatings grafting gentamicin loaded
      collagen were examined by simulated body fluid (SBF) soaking test and in vitro
      cell culture test. The release rate of gentamicin from collagen was measured
      using UV spectrophotometer in phosphate-buffered saline (PBS) and the
      antibacterial activity against Staphylococcus aureus (S. aureus) was evaluated by
      zone of inhibition test and bacterial counting method. The results showed that a
      composite layer with collagen and silicon-rich particles was formed on the
      surface of the coating after the graft of collagen. The grafted collagen layer
      mixed with silicon-rich particles could induce the precipitation of apatite after
      soaking in SBF for 14 days and improved the cellular proliferation on
      wollastonite coatings. The release of gentamicin from the collagen layer
      sustained 11 days in PBS and effectively inhibited the growth of S. aureus. In
      conclusion, the wollastonite coating grafting gentamicin loaded collagen had
      excellent bioactivity and cytocompatibility as well as good antibacterial
      properties, which would be beneficial for the long term stability and surgical
      success rate of implants.

PMID- 18085658
TI  - Gene expression analysis of osteoblasts seeded in coral scaffold.
AB  - Coral matrix of Porites sp. has the suitable properties for bone cell growth.
      This study was aimed to study the gene expression levels of osteoblast specific
      genetic markers; RUNX2, osteopontin, alkaline phosphatase and osteocalcin from
      osteoblasts seeded in coral scaffold, which are important in determining the
      feasibility of osteoblasts. Human osteoblasts were inoculated onto the processed
      coral in Dulbecco's Minimum Essential Medium. The cells were trypsinized on day
      1, 7, 14, 18, and 21 and added with RNALater for preservation of RNA in cells.
      The RNA was extracted using commercial RNA extraction kit and the respective
      genes were amplified using RT-PCR kit and analyzed qualitatively on 1.5% agarose
      gel. The expressions were evaluated with the Integrated Density Value based on
      the intensity of band for different periods of cell harvest. Increased
      expressions of the RUNX2, osteopontin, alkaline phosphatase and osteocalcin genes
      in the present study proved that coral is a favorable carrier for
      osteogenetically competent cells to attach and remain viable.

PMID- 18085659
TI  - Novel biostable and biocompatible amphiphilic membranes.
AB  - We determined the biostability and biocompatibility of two types of amphiphilic
      conetworks (APCNs): (1) hydrophilic poly(N,N-dimethyl acrylamide) (PDMAAm) and
      hydrophobic polydimethylsiloxane (PDMS) microdomains co-crosslinked with
      polymethylhydrosiloxane (PMHS) clusters (PDMAAm/PMHS/PDMS), and (2) poly(ethylene
      glycol) (PEG) and PDMS microdomains co-crosslinked with two specially designed
      small-molecule crosslinking agents SiC(6)H(5)(SiH)(2)OEt (Y) and
      polypentamethylhydrocyclosiloxane (PD(5)) (PEG/Y or PD(5)/PDMS). Negative
      standards for comparing biocompatibility and biostability were crosslinked PDMS.
      Biostability was assessed by quantitatively determining extractables, equilibrium
      water swelling, mechanical properties (stress-strain response) of polymer samples
      before and after implantation in rats for up to 8 weeks, and oxidative
      accelerated degradation test. Biocompatibility was assessed by determining body
      weight, fibrous tissue encapsulation, fluid accumulation, and by histological
      evaluation of lymphocyte infiltration, fibrous tissue accumulation and collagen
      deposition. According to these stringent metrics PDMAAm/PMHS/PDMS is both
      biostable and biocompatible, whereas PEG/Y or PD(5)/PDMS degrades in living
      tissue but is biocompatible. Surprisingly, the overall biocompatibility scores of
      these APCNs were superior to those of the PDMS negative standard.

PMID- 18085660
TI  - Elicitation of a beta prior for Bayesian inference in clinical trials.
AB  - When making Bayesian inferences we need to elicit an expert's opinion to set up
      the prior distribution. For applications in clinical trials, we study this
      problem with binary variables. A critical and often ignored issue in the process
      of eliciting priors in clinical trials is that medical investigators can seldom
      specify the prior quantities with precision. In this paper, we discuss several
      methods of eliciting beta priors from clinical information, and we use
      simulations to conduct sensitivity analyses of the effect of imprecise assessment
      of the prior information. These results provide useful guidance for choosing
      methods of eliciting the prior information in practice.

PMID- 18085661
TI  - Critical role for IFN-gamma in natural killer cell-mediated protection from
      diabetes.
AB  - Autoimmune diabetes in nonobese diabetic (NOD) mice can be prevented by a single
      injection of complete Freund's adjuvant (CFA), but the mechanisms mediating
      protection remains unclear. We previously showed that NOD mice immunized with CFA
      have a markedly reduced incidence of diabetes that is associated with a
      significant decrease in the number of beta-cell-specific, autoreactive cytotoxic
      T lymphocytes and, furthermore, that the effect of CFA is mediated by natural
      killer (NK) cells. In this study, we report one mechanism by which NK cells
      regulate the onset of diabetes. Administration of CFA produced a rapid increase
      in NK cell frequency and function, including cytotoxicity and IFN-gamma
      secretion. By co-transferring NK cells from IFN-gamma-deficient (or wild-type)
      NOD mice and spleen cells from diabetic NOD mice to NOD/SCID recipients, we show
      that IFN-gamma secretion by NK cells significantly influences the effect of CFA
      protection. In contrast, NK cytotoxicity does not appear to participate in CFA
      mediated protection from diabetes. Our findings demonstrate that NK cells mediate
      the protective effects of CFA through secretion of IFN-gamma.

PMID- 18085662
TI  - The orally-active and selective c-Fms tyrosine kinase inhibitor Ki20227 inhibits
      disease progression in a collagen-induced arthritis mouse model.
AB  - Macrophage colony-stimulating factor (M-CSF) is important in the development of
      macrophages and osteoclasts. Previous studies have also shown that CD11b(+)
      myeloblasts and osteoclasts play key roles during inflammation and bone
      destruction in arthritic lesions. In this study, we investigated whether N-{4
      [(6,7-dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N'-[1-(1,3-thiazole-2-yl)ethyl]
      urea (Ki20227), an inhibitor of the M-CSF receptor (c-Fms), suppressed disease
      progression in a type II collagen (CII)-induced arthritis (CIA) mouse model. We
      found that Ki20227 inhibited M-CSF-dependent reactions, such as
      lipopolysaccharide-induced tumor necrosis factor-alpha production, which were
      enhanced by M-CSF in vitro. Oral administration of Ki20227 in vivo prevented
      inflammatory cell infiltration and bone destruction, and consequently suppressed
      disease progression. In addition, the number of CD11b(+), Gr-1(+), and Ly-6G(+)
      cells in the spleen decreased in the Ki20227-treated mice, and the CII-induced
      cytokine production in splenocytes isolated from the Ki20227-treated arthritic
      mice was also reduced. These observations indicate that Ki20227 might exert its
      therapeutic effects in the CIA mouse model by suppressing the M-CSF-dependent
      accumulation of both inflammatory and osteoclast cells, as well as by inhibiting
      inflammatory cytokine production. Hence, inhibitors of the c-Fms tyrosine kinase
      might act as anti-inflammatory or anti-osteolytic agents against arthritis.

PMID- 18085663
TI  - A displaced PAG enhances proximal signaling and SDF-1-induced T cell migration.
AB  - PAG, the phosphoprotein associated with glycosphingolipid-enriched microdomains
      (GEM), negatively regulates Src family kinases by recruiting C-terminal Src
      kinase (Csk) to the membrane, where Csk phosphorylates the inhibitory tyrosine of
      the Src kinases. S-acylation of a CxxC motif juxtaposed to the transmembrane
      domain within PAG has been proposed to be responsible for targeting PAG to the
      lipid rafts. Here, we present the characterization of a mutant PAG molecule
      lacking the palmitoylation motif. We demonstrate that the mutant protein is
      expressed at the plasma membrane, but does not localize within the GEM. Despite
      being displaced, the mutant PAG molecule still binds the Src kinase Fyn and the
      cytoskeletal adaptor ezrin-radixin-moesin-binding phosphoprotein of 50 kDa,
      becomes tyrosine-phosphorylated, and recruits Csk to the membrane. Functional
      characterization of the mutant shows that, unlike WT PAG, it does not block
      proximal TCR signaling, and surprisingly enhances stromal cell-derived factor 1
      (CXCL12)-induced migration. The mutant functions by depleting Csk from the GEM
      fractions, as apparent by changes in the phosphorylation of the inhibitory
      tyrosines within the Src kinases. Indeed this mechanism is supported by RNA
      interference of PAG, which results in enhanced migration and Src kinase activity.
      Our results therefore support a functional role for the compartmentalization of
      Src kinases within the membrane.

PMID- 18085664
TI  - Notch signaling is activated by TLR stimulation and regulates macrophage
      functions.
AB  - Notch signaling is a well-conserved pathway involved in cell fate decisions,
      proliferation and apoptosis. We report on the involvement of Notch signaling in
      regulating gene expression in activated macrophages. Toll-like receptors (TLR)
      agonists such as bacterial lipopeptide, polyI:C, lipopolysaccharide and
      unmethylated CpG DNA all induced up-regulation of Notch1 in primary and
      macrophage-like cell lines. Notch1 up-regulation was dependent on the MyD88
      pathway when stimulated through TLR2, but not TLR4. Activated Notch1 and
      expression of the Notch target genes, Hes1 and Deltex, were detected in activated
      macrophages, suggesting that Notch signaling was activated upon stimulation.
      Inhibiting processing of Notch receptor by gamma-secretase using a gamma
      secretase inhibitor (GSI), the expression of Notch1 was down-regulated to basal
      levels. This treatment significantly modulated expression of TNF-alpha, IL-6, and
      IL-10. In addition, the amount of nitric oxide produced was significantly lower
      and the expression of MHC class II was up-regulated in GSI-treated cells.
      Treatment with GSI or silencing Notch1 resulted in decreased translocation of NF
      kappaBp50 into nucleus upon stimulation. Taken together, stimulation of
      macrophages through the TLR signaling cascade triggered activation of Notch
      signaling, which in turn regulated gene expression patterns involved in pro
      inflammatory responses, through activation of NF-kappaB.

PMID- 18085665
TI  - Phagocytosis-induced apoptosis of macrophages is linked to uptake, killing and
      degradation of bacteria.
AB  - Phagocytosis and intracellular destruction of pathogens by phagocytes is a
      crucial defense mechanism of the innate immune response during infection. It has
      been reported a number of times that the interaction with pyogenic, extracellular
      bacteria leads to the apoptotic death of phagocytes. The signaling events that
      cause this form of cell death are largely unknown. In this study, we demonstrate
      a link between uptake, killing and degradation of Escherichia coli bacteria and
      induction of apoptosis in macrophages. Treatment of murine RAW 264.7 macrophages
      with bafilomycin A(1), a phagosome acidification inhibitor, reduced killing and
      degradation of phagocytosed bacteria and significantly decreased macrophage
      apoptosis. The stable overexpression of constitutively active or dominant
      negative mutants of the small GTPase Rab5a increased bacterial phagocytosis and
      consecutively apoptosis. In these cells, relative killing and degradation were
      not affected, linking the increased apoptosis to enhanced uptake and suggesting
      that the apoptosis-inducing signal derives from the higher incidence of
      degradation events or an accumulation of phagosomes of a late maturation stage.
      These results thus provide a link between bacterial phagocytosis and degradation
      and the induction of apoptosis in macrophages. We propose that this form of
      apoptosis is the physiological conclusion of an innate immune response against
      pyogenic bacteria.

PMID- 18085666
TI  - RIP2 contributes to Nod signaling but is not essential for T cell proliferation,
      T helper differentiation or TLR responses.
AB  - Receptor-interacting protein 2 (RIP2), also known as CARDIAK and RICK, has been
      reported to play a role in both adaptive T cell responses and innate immunity as
      a mediator in TLR signaling and nucleotide-binding oligomerization domain (Nod)
      signaling. Because initial reports remain controversial, we have further examined
      both innate and adaptive immune responses in RIP2-deficient mice on the C57BL/6
      background. Despite the up-regulation of RIP2 after T cell activation, we could
      not detect any defect in T cell proliferation or Th1/Th2 responses in RIP2-KO
      mice. Furthermore, we found that TLR responses in RIP2-deficient macrophages were
      normal. However, our analysis showed that Nod signaling was impaired in
      macrophages from RIP2-deficient mice. In conclusion, our data demonstrate a
      critical role for RIP2 in Nod signaling, while T cell proliferation, T helper
      differentiation and TLR responses were unaffected by the absence of RIP2.

PMID- 18085667
TI  - Endotoxin hyperresponsiveness upon CD4+ T cell reconstitution in lymphopenic
      mice: control by natural regulatory T cells.
AB  - Natural CD4(+)CD25(+) regulatory T cells (nTreg) have been shown to control graft
      versus-host disease after hematopoietic stem cell transplantation (HSCT). Herein,
      we considered the possibility that the beneficial action of nTreg upon immune
      reconstitution in lymphopenic hosts involves dampening of the inflammatory
      response induced by bacterial products. We first observed that transfer of
      syngeneic CD4(+)CD25(-) T cells in RAG-deficient mice dramatically enhanced
      release of inflammatory cytokines and associated pathology upon endotoxin
      injection. Interferon (IFN)-gamma produced by T cells undergoing homeostatic
      proliferation was shown to be involved in the endotoxin hyperresponsiveness
      induced by CD4(+) T cell reconstitution. Co-transfer of CD4(+)CD25(+) nTreg with
      CD4(+)CD25(-) T cells inhibited the expansion of IFN-gamma-producing T cells and
      reduced endotoxin responses in RAG(-/-) mice. We conclude that (1) CD4(+) T cell
      reconstitution sensitizes lymphopenic hosts to endotoxin-induced pathology and
      (2) nTreg prevent this process by limiting the emergence of IFN-gamma-producing
      cells.

PMID- 18085668
TI  - Levels of autoantibodies, unlike antibodies to all extrinsic antigen groups, fall
      following B cell depletion with Rituximab.
AB  - Many autoantibodies have variable-region sequences indicating their production in
      an affinity-matured antibody response involving germinal centers (GC). Plasma
      cells from GC can be long-lived, do not express CD20 and thus should not be
      depleted by a therapeutic monoclonal Ab against human CD20 - Rituximab.
      Nevertheless, autoantibody titers often fall following Rituximab treatment. To
      test if this reflects exclusive production by short-lived plasma cells in
      extrafollicular Ab responses, we monitored, after Rituximab treatment, levels of
      natural Ab and Ab against extrinsic antigens that do not induce productive GC.
      Eleven patients with active vasculitis and anti-proteinase-3 (PR3) Ab were
      assessed before and during 5 months after Rituximab therapy. Blood B cells were
      undetectable within 2 wk, and all patients achieved clinical remission. Levels of
      natural Ab - isohemagglutinins and anti-phosphorylcholine Ab - and Ab levels
      against thymus-independent and thymus-dependent extrinsic antigens were little
      affected. By contrast, 5 months after Rituximab, IgG autoantibody against PR3 had
      fallen to a median of 22% of pretreatment values. While the kinetics of this fall
      do not suggest an intrinsically short lifespan of autoantibody-producing cells,
      the data are consistent with Rituximab causing loss of sites within inflammatory
      tissues that selectively sustain autoantibody-producing cells.

PMID- 18085669
TI  - Apoptosis differentially regulates mesenteric and subcutaneous lymph node immune
      responses to Trypanosoma cruzi.
AB  - Infection with Trypanosoma cruzi causes expansion of subcutaneous (SLN) and
      atrophy of mesenteric (MLN) lymph nodes. Here we show that excision of MLN
      increased parasitemia in T. cruzi-infected mice. We then studied how apoptosis of
      MLN cells affects immune responses to infection. T cell apoptosis increased in
      the MLN compared to SLN in T. cruzi-infected mice. Absolute numbers of naive T
      cells decreased, and activated T cells failed to accumulate in MLN during
      infection. In addition, activated T cells from MLN produced less IL-2, IFN-gamma,
      IL-4, and IL-10 than T cells from SLN. Treatment with IL-4 or with caspase-9
      inhibitor increased the recovery of viable T cells in vitro. Treatment with
      caspase-9 inhibitor also increased the production of cytokines by MLN T cells
      from infected mice. Moreover, injection of a pan caspase inhibitor prevented MLN
      atrophy during T. cruzi infection. Caspase-9, but not caspase-8, inhibitor also
      reduced MLN atrophy and increased the recovery of naive and activated T cells
      from MLN. These findings indicate that caspase-mediated apoptosis and defective
      cytokine production are implicated in MLN atrophy and affect immune responses to
      T. cruzi infection.

PMID- 18085670
TI  - Retinoid receptor-activating ligands are produced within the mouse thymus during
      postnatal development.
AB  - Vitamin A deficiency is known to be accompanied with immune deficiency and
      susceptibility to a wide range of infectious diseases. Experimental evidence
      suggests that the active metabolites of vitamin A that mediate its effects on the
      immune system are the retinoic acids (RA), which are ligands for the nuclear RA
      receptor (RAR) family. RA were previously shown both to promote proliferation and
      to regulate apoptosis of thymocytes. In this study we detected the age-dependent
      mRNA expression of retinaldehyde dehydrogenases (RALDH1 and 2), cellular RA
      binding protein-II and CYP26A, proteins responsible for the synthesis, nuclear
      transport and degradation of RA in the postnatally developing thymus. RALDH1 was
      located in thymic epithelial cells. However, the amount of all-trans RA in thymic
      homogenates was close to the detection limit, suggesting that in this tissue all
      trans RA is not the main RAR-regulating product of retinol metabolism. At the
      same time, by measuring the induction of a RAR-responsive transgene in two
      independent transgenic mouse strains, we demonstrated the production of an RAR
      activating ligand, which was age and RALDH dependent. Our data provide evidence
      for the existence of endogenous retinoid synthesis in the thymus and suggest that
      retinoids similar to glucocorticoids might indeed be involved in the regulation
      of thymic proliferation and selection processes by being present in the thymus in
      functionally effective amounts.

PMID- 18085671
TI  - Pulmonary alveolar proteinosis in pediatric leukemia.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized
      by intra-alveolar accumulation of periodic acid-Schiff (PAS)-positive surfactant
      components. Leukemia is the cancer most often associated with PAP; prolonged
      neutropenia and reduction of alveolar macrophages by myeloablative chemotherapy
      or leukemic infiltration are implicated. Only isolated cases of PAP have been
      reported, and pediatric experience is limited. PROCEDURE: We reviewed all
      pathology records (1962-2007) of St. Jude Children's Research Hospital to
      identify patients with PAP. RESULTS: Five patients had PAP. As expected, all had
      leukemia and had profound neutropenia at onset of PAP. A diagnosis was made only
      after PAS staining of bronchoalveolar lavage (BAL), lung biopsy, or autopsy
      specimens. Two patients had Down syndrome, which is not known to be associated
      with PAP. The other three patients had undergone hematopoietic stem cell
      transplantation (HSCT). Two patients showed clinical improvement or histological
      disappearance of PAP after neutropenia resolved. CONCLUSIONS: PAP should be
      considered in the differential diagnosis of severe respiratory symptoms in
      neutropenic patients with hematologic malignancy, especially those with Down
      syndrome, a history of HSCT, or active disease. PAP should be confirmed by PAS
      staining of a BAL or lung biopsy specimen.

PMID- 18085672
TI  - Evaluation of a comprehensive transcranial doppler screening program for children
      with sickle cell anemia.
AB  - BACKGROUND: Although transcranial Doppler ultrasonography (TCD) screening is
      effective in identifying children with sickle cell anemia (SCA) who are at high
      risk of stroke, not all children are screened. In 2003, we instituted a
      comprehensive TCD screening program designed to screen all at-risk children
      treated at our sickle cell center. PROCEDURE: We evaluated the efficacy of our
      program by comparing the number of patients screened per year and incidence of
      first stroke across three periods defined by TCD usage: (1) pre-dating TCD
      screening, (2) sporadic TCD screening, and (3) comprehensive TCD screening.
      RESULTS: During Period 2, an average of 52 patients/year were screened. In Period
      3, an average of 95 patients/year were screened representing 99% of the at-risk
      population. Eighteen strokes occurred in Period 1, 22 in Period 2 and three in
      Period 3. The first stroke incidence was significantly lower in Period 3 compared
      to Periods 1 and 2 (P = 0.047). Furthermore, of the 25 patients in Periods 2 and
      3 who had stroke, only six had received TCD screening (four in Period 2, two in
      Period 3). These six either declined prophylactic transfusion therapy (n = 2),
      had co-existing stroke risk factors (n = 2), or did not return for appropriate
      TCD follow-up (n = 2). Therefore, strokes that occurred were not the result of a
      failure of TCD screening per se. CONCLUSIONS: It is possible to perform TCD
      screening of most children with SCA. TCD screening is effective in reducing first
      stroke incidence in these children.

PMID- 18085673
TI  - Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical
      testing program.
AB  - BACKGROUND: ABT-263 is a potent (K(i) < 1 nM) small-molecule BH3 mimetic that
      inhibits the antiapoptotic proteins Bcl-2, Bcl-x(L) and Bcl-w. The structurally
      related Bcl-2 inhibitor ABT-737 exhibits single-agent preclinical activity
      against lymphoma, small-cell lung carcinoma, and chronic lymphocytic leukemia and
      displays synergistic cytotoxicity with chemotherapeutics and radiation. METHODS:
      ABT-263 was tested at concentrations ranging from 1.0 nM to 10.0 microM using 23
      cell lines from the PPTP in vitro panel and was tested in 44 xenograft models
      representing nine distinct histologies using daily gavage administration of ABT
      263 (100 mg/kg) or vehicle for 21 days. RESULTS: ABT-263 was active against
      approximately one-half of the cell lines of the PPTP in vitro panel. The median
      IC(50) for all of the lines in the panel was 1.91 microM. ABT-263 induced
      significant prolongation of the EFS distribution in 9 of 35 (26%) of the solid
      tumor xenografts, and in 5 of 6 (83%) of the evaluable ALL xenografts. ABT-263
      induced no objective responses in the solid tumor panels, but induced CRs in 3 of
      6 evaluable xenografts in the ALL panel, including two that were maintained for
      an additional 3 weeks following treatment cessation. CONCLUSIONS: ABT-263
      demonstrated in vitro activity against a range of cell lines, with the ALL cell
      lines showing the greatest sensitivity. ABT-263 demonstrated limited single agent
      in vivo activity against the PPTP's solid tumor panels but showed significant
      activity against xenografts in the ALL panel.

PMID- 18085674
TI  - Complete response to imatinib mesylate treatment in a 12-month-old patient with
      chronic myeloid leukemia.

PMID- 18085675
TI  - Application of the adult international germ cell classification system to
      pediatric malignant non-seminomatous germ cell tumors: a report from the
      Children's Oncology Group.
AB  - BACKGROUND: The purpose of this analysis is to explore whether the International
      Germ Cell Classification Consensus (IGCCC) tumor marker criteria, developed for
      adult males with metastatic malignant germ cell tumors (MGCT), are prognostic
      among pediatric patients and whether tumor marker data may be relevant in
      pediatric risk stratification. PROCEDURE: The IGCCC was applied to 436 pediatric
      germ cell patients treated on Pediatric Intergroup Studies from 1990 to 1996.
      Multivariable Cox proportional hazards model identified prognostic variables;
      survival rates among IGCCC risk groups were compared using the log-rank test.
      Concordance and relative performance of IGCCC versus COG risk stratification was
      evaluated. RESULTS: Applying the IGCCC, 21% of pediatric patients were good risk
      (GR), 35% intermediate risk (IR), and 44% poor risk (PR). Only modest concordance
      between IGCCC and COG stratification systems was noted (49%). Nonetheless, the
      IGCCC identified a group of PR patients who had significantly worse event-free
      survival (EFS) versus GR/IR patients (6-year EFS 80% vs. 91%), which was similar
      to the difference observed using the COG system (6-year EFS 77% vs. 90%). The
      IGCCC performed well within subgroups for which the IGCCC is not intended
      (prepubertal, female, and non-metastatic patients). CONCLUSIONS: Applying the
      IGCCC system to pediatric patients produces a different stratification than does
      the application of the COG system, although both are prognostic. Development of a
      de novo pediatric prognostic classification is warranted.

PMID- 18085676
TI  - Highly elevated ferritin levels and the diagnosis of hemophagocytic
      lymphohistiocytosis.
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a potentially lethal
      condition characterized by a pathologic inflammation. The diagnostic criteria for
      HLH include fever, splenomegaly, cytopenias, hypertriglyceridemia,
      hypofibrinogenemia, abnormal natural killer cell (NK cell) functional assay,
      elevated soluble IL-2Ralpha level, and elevated ferritin level (>500 microg/L).
      Institution of timely therapy in these critically ill patients may be delayed by
      difficulties establishing the diagnosis. NK cell functional assay and soluble IL
      2Ralpha level may require send-out to a specialized lab. However, ferritin level
      is available on a same-day basis at most institutions. In this study, we examined
      the utility of quantitative ferritin levels in diagnosing HLH. PROCEDURE: All
      patients with ferritin values >500 microg/L obtained at Texas Children's Hospital
      between January 10, 2003 and January 10, 2005 were identified. Patient charts
      were reviewed for ferritin levels and hospital course. RESULTS: During the study
      interval, 330 patients had ferritin levels >500 microg/L. Ten of the 330 patients
      were diagnosed with HLH. A ferritin level over 10,000 microg/L was 90% sensitive
      and 96% specific for HLH. Another diagnostic category with significantly elevated
      ferritin level was illness of unknown cause (n = 10), and only two of these
      patients were fully evaluated for HLH. CONCLUSIONS: Ferritin levels above 10,000
      microg/L appear to be specific and sensitive for HLH. In patients without a
      significant medical history and a new onset of febrile illness with highly
      elevated ferritin levels, the diagnosis of HLH should be evaluated.

PMID- 18085680
TI  - Bronchial asthma and acute lymphoblastic leukemia in childhood.

PMID- 18085681
TI  - A new standardized treadmill walking test requiring low motor skills in children
      aged 4-10 years.
AB  - Exercise intolerance may be reported by parents of young children with
      respiratory diseases. There is, however, a lack of standardized exercise
      protocols which allow verification of these reports especially in younger
      children. Consequently the aims of this pilot study were to develop a
      standardized treadmill walking test for children aged 4-10 years demanding low
      sensorimotor skills and achieving high physical exhaustion. In a prospective
      experimental cross sectional pilot study, 33 healthy Caucasian children were
      separated into three groups: G1 (4-6 years, n = 10), G2 (7-8 years, n = 12), and
      G3 (9-10 years, n = 11). Children performed the treadmill walking test with
      increasing exercise levels up to peak condition with maximal exhaustion. Gas
      exchange, heart rate, and lactate were measured during the test, spirometry
      before and after. Parameters were statistically calculated at all exercise levels
      as well as at 2 and 4 mmol/L lactate level for group differences (Kruskal-Wallis
      H-test, alpha = 0.05; post hoc: Mann-Whitney U-test with Bonferroni correction
      alpha = 0.05/n) and test-retest differences (Wilcoxon-rank-sum test) with SPSS.
      The treadmill walking test could be demonstrated to be feasible with a good
      repeatability within groups for most of the parameters. All children achieved a
      high exhaustion level. At peak level under exhaustion condition only the absolute
      VO2 and VCO2 differed significantly between age groups. In conclusion this newly
      designed treadmill walking test indicates a good feasibility, safety, and
      repeatability. It suggests the potential usefulness of exercise capacity
      monitoring for children aged from early 4 to 10 years. Various applications and
      test modifications will be investigated in further studies.

PMID- 18085682
TI  - The congenital porto-caval fistula: a unique presentation and novel intervention.
AB  - Congenital porto-caval fistulas are uncommon vascular malformations with a varied
      clinical presentation beginning in infancy and spanning late adulthood. We report
      a 14-year-old male who presented with dyspnea and cough. His past medical history
      was significant for a chronic non-immune hemolytic anemia, thrombocytopenia,
      coagulopathy and a learning disability. He was found to have severe pulmonary
      hypertension and hyperammonemia associated with a large congenital porto-caval
      fistula. The abnormal vessel was occluded via endovascular covered stent
      placement in the vena cava. His pulmonary hypertension has improved remarkably
      while his chronic anemia, thrombocytopenia and ammonia have normalized to allow
      improved cognitive performance.

PMID- 18085683
TI  - A multiplex PCR-based reverse line blot hybridization (mPCR/RLB) assay for
      detection of bacterial respiratory pathogens in children with pneumonia.
AB  - OBJECTIVES: To develop and evaluate a novel method for simultaneous
      identification of 12 potential bacterial pathogens in children with community
      acquired pneumonia. METHODS: A multiplex PCR-based reverse line blot (mPCR/RLB)
      assay was developed, to identify 12 respiratory bacterial pathogens, namely
      Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes,
      Moraxella catarrhalis, Haemophilus influenzae, Haemophilus influenzae type b,
      Bordetella pertussis, Klebsiella pneumoniae, Legionella pneumophila,
      Mycobacterium tuberculosis, Chlamydia pneumoniae, Mycoplasma pneumoniae, and
      single (uniplex) PCRs were used for S. pneumoniae and H. influenzae only. In a
      preliminary evaluation, we compared the results of mPCR/RLB with those of single
      (uniplex) PCRs and culture of nasopharyngeal aspirates (NPAs) from 100 children
      under 5 years, admitted to Beijing Children's Hospital between October 2004 and
      May 2005, with pneumonia. RESULTS: Reference strains and clinical isolates of all
      12 target species were correctly identified by mPCR/RLB. Potential pathogens were
      isolated from one blood culture and 26% of respiratory cultures. One or more
      pathogens were identified in 70% of respiratory specimens--by mPCR/RLB in 63%,
      uPCR only in another 3%, culture only in 2%, and culture plus uPCR in 2%. The
      species most commonly identified were S. pneumoniae (54%) and H. influenzae (38%,
      including type b, 4%). Cultures were not performed for B. pertussis, M.
      tuberculosis, C. pneumoniae or M. pneumoniae but each was identified by mPCR/RLB
      in between one and four specimens. Two or more potential pathogens were
      identified in 35% of specimens. Ten of 14 S. pneumoniae isolates belonged to
      serotypes represented in the 11-valent pneumococcal conjugate vaccine.
      CONCLUSIONS: The mPCR/RLB assay is a sensitive tool for identification of
      respiratory pathogens, including mixed infections and bacteria requiring special
      culture methods.

PMID- 18085684
TI  - Effect of race on vincristine-associated neurotoxicity in pediatric acute
      lymphoblastic leukemia patients.
AB  - BACKGROUND: This report examines the association between race and vincristine
      associated neurotoxicity in pediatric patients with precursor B cell acute
      lymphoblastic leukemia (preB ALL). Given that in vitro vincristine is metabolized
      more efficiently by cytochrome P450 (CYP) 3A5 than by CYP3A4 and that 70% African
      Americans (vs. 20% of Caucasians) express CYP3A5, one may hypothesize that
      African-Americans metabolize vincristine more efficiently resulting in lower
      vincristine exposure and associated-toxicity. PROCEDURE: A retrospective analysis
      of vincristine-related side effects in pediatric patients treated for preB ALL
      was performed. Data were compared between Caucasians (n = 92) and African
      Americans (n = 21) to examine the relationship between race and vincristine
      associated neurotoxicity thus using race as a surrogate for CYP3A5 genotype.
      Race, age, gender, disease subtype, highest grade of vincristine-associated
      neurotoxicity (per NIH Common Terminology Criteria for Adverse Events version
      3.0), number of omitted and reduced vincristine doses, cumulative vincristine
      dose, and disease outcome were captured. RESULTS: 34.8% of Caucasians experienced
      symptoms consistent with vincristine-related neurotoxicity compared to 4.8% of
      African-Americans (P = 0.007). The average grade of neurotoxicity for Caucasians
      was 2.72 versus grade 1 neurotoxicity in the African-American (P < 0.0001). Four
      percent of total doses administered to Caucasian patients were reduced due to
      vincristine-related neurotoxicity compared to 0.1% given to African-Americans (P
      < 0.0001). 1.2% of all protocol-indicated doses for Caucasians were held due to
      severe vincristine-associated toxicity compared to 0.1% of doses for African
      Americans (P < 0.01). CONCLUSIONS: The data support the hypothesis
      pharmacogenetic polymorphisms in CYP3A5 expression contribute to variability in
      vincristine metabolism and neurotoxicity.

PMID- 18085687
TI  - Transfer of complex frontline anticancer therapy to a developing country: the St.
      Jude osteosarcoma experience in Chile.
AB  - BACKGROUND: A frontline protocol for newly diagnosed osteosarcoma was conducted
      simultaneously at St. Jude Children's Research Hospital (sponsor) and Calvo
      Mackenna Hospital (CMH, partner), a public pediatric hospital and national center
      for the treatment of bone tumors in Santiago, Chile. PROCEDURE: Of 72 eligible
      patients, 22 (31%) were enrolled and managed in Santiago, without travel to
      Memphis. Pathology specimens and imaging material were centrally reviewed at St.
      Jude. Patients received 12 intensive courses of systemic chemotherapy with
      hematopoietic growth factor support over 35 weeks, and amputation or limb-salvage
      surgery as indicated for local control. The sponsor assisted the partner site to
      establish a clinical research infrastructure and obtain hematopoietic growth
      factor. Communication among medical and nursing teams was maintained throughout
      the study. Patient-care and protocol issues were discussed frequently between the
      two centers via scheduled videoconferences and electronic communications.
      Auditors monitored appropriate study conduct at the international site. RESULTS:
      No major discrepancies were identified in histologic findings, staging, or
      imaging studies. Preliminary results demonstrated similar outcome and treatment
      tolerance; the 2-year event-free survival estimate was 78.5% (95% CI, 51-100%)
      for patients treated at CMH (median follow-up, 1.6 years) and 74.3% (95% CI, 62
      87%) for patients treated at St. Jude (median follow-up, 4 years). Overall per
      patient costs were significantly lower in Chile. CONCLUSIONS: Through a twinning
      mechanism, it is feasible to simultaneously conduct complex front-line
      osteosarcoma clinical trials at two institutions in countries with different
      levels of resources.

PMID- 18085688
TI  - Recognition and treatment of neonatal community-associated MRSA pneumonia and
      bacteremia.
AB  - Community-associated strains of methicillin-resistant Staphylococcus aureus (CA
      MRSA) have recently emerged as a major cause of serious infections among older
      children and are now being seen in NICU patients. We present the case of a
      preterm infant with CA-MRSA necrotizing pneumonia and secondary bacteremia.

PMID- 18085689
TI  - Impact of childhood cancer on parental employment and sources of income: a
      Canadian pilot study.
AB  - BACKGROUND: Loss of income and out of pocket expenses related to childhood cancer
      care can account for over 25% of a family's total disposable income, adding to
      the stress of facing a life-threatening disease. The objective of this pilot
      study was to assess the impact of childhood cancer on employment and sources of
      income within families. PROCEDURE: A retrospective postal-administered
      questionnaire was used to collect information from parents of children diagnosed
      with cancer before 20 years of age between 1990 and 1996 in the province of
      British Columbia (n = 111). RESULTS: Among full or part-time employed parents,
      64% of mothers and 16% of fathers left their job after their child's diagnosis.
      The large majority of parents who left their jobs were away for less than 1 year
      (65% of mothers; 78% of fathers) and nearly all were able to return to the same
      job if they chose to do so (80% of mothers; 89% of fathers). Parents with
      children <10 years of age at diagnosis and those with leukemia were most likely
      to take leave from their jobs. There was considerable change in sources of income
      between the time of diagnosis and survey with more families relying on employment
      insurance, social assistance or other financial support at diagnosis. Reliance on
      sources of income other than salary decreased with time since diagnosis.
      CONCLUSIONS: It appears that the diagnosis of childhood cancer may cause an
      important but short-term impact on the employment and income sources of affected
      families.

PMID- 18085690
TI  - Glucocorticoid receptor disruption delays structural maturation in the lungs of
      newborn mice.
AB  - In order to better understand the regulation of lung maturation by glucocorticoid
      glucocorticoid receptor signaling, we studied glucocorticoid receptor (GR)
      hypomorphic mice with a mixed C57Bl6/129 sv background, in which disruption of
      exon 2 of the GR gene produces an N-terminal truncated GR protein. Four groups of
      mice were compared: homozygous mice that die at birth (non-survivors), homozygous
      mice that survive the neonatal period (survivors), heterozygotes and wild-type
      mice. Newborn non-survivors had 50% thicker airspace walls and a 46% decrease in
      the formation of secondary crests (the beginning of alveolar secondary septation)
      compared to either survivor or wild-type littermates (n = 9 mice in each group).
      The lung tissue to airspace ratio in homozygous mice not expressing wild-type GR
      (non-survivor and survivor) was increased compared to heterozygotes and wild-type
      mice that do express wild-type GR (0.91 +/- 0.08 vs. 0.49 +/- 0.02, n = 4 in each
      of the four subgroups), suggesting that complete morphological maturation of the
      lung is dependent on effective glucocorticoid signaling through a fully
      functional GR. Moreover, the relatively mature lung morphology of survivor versus
      non-survivor newborns suggests that a partial reduction in mesenchymal thickness
      is compatible with capillary remodeling, alveolar septation, and viable
      respiratory function after birth. Our findings suggest that in mice homozygous
      for disrupted GR, the severity of newborn respiratory insufficiency correlates
      with the degree of lung structural immaturity.

PMID- 18085691
TI  - Sudden death due to pulmonary embolism as presenting symptom of renal tumors.
AB  - In 4-6% of patients with renal tumors in children intravascular infiltration is
      found. Tumor emboli are even rarer, and sudden death as presenting symptom has
      only been described at presentation in Wilms tumor (WT) in six cases so far. This
      report describes two recent cases of sudden death in patients with renal tumors
      in which a fatal pulmonary embolus was the first presentation.

PMID- 18085693
TI  - Low grade fibromyxoid sarcoma and neurofibromatosis type I.

PMID- 18085692
TI  - Exhaled nitric oxide for monitoring childhood asthma inflammation compared to
      sputum analysis, serum interleukins and pulmonary function.
AB  - The level of fractional exhaled nitric oxide (FENO) is significantly elevated in
      uncontrolled asthma and decreases after anti-inflammatory therapy. The aim of
      this prospective study was to analyze the behavior of FENO in the follow-up and
      management of the inflammation in asthmatic pediatric patients treated with
      inhaled corticosteroids (ICS), compared to sputum cellularity, serum interleukins
      (IL), and pulmonary function. Twenty-six clinically stable asthmatic children
      aged from 6 to 18 years, previously treated or not with ICS were included.
      Following an international consensus (GINA), the patients were submitted to
      standard treatment with inhaled fluticasone for 3 months according to the
      severity of the disease. During this period, each patient underwent three
      assessments at intervals of approximately 6 weeks. Each evaluation consisted of
      the measurement of FENO, determination of serum interleukins IL-5, IL-10, IL-13,
      and interferon gamma (INF-gamma), spirometry and cytological analysis of
      spontaneous or induced sputum. A significant reduction in mean FENO and IL-5,
      without concomitant changes in FEV1, was observed along the study. There was no
      significant correlation between FeNO and FEV1 in the three assessments. A
      significant correlation between FeNO and IL-5 levels was only observed in the
      third assessment (r = 0.499, P = 0.025). In most patients, serum IL-10, IL-13,
      and INF-gamma concentrations were undetectable throughout the study. Sputum
      samples were obtained spontaneously in 11 occasions and in 56 by induction with
      3% hypertonic saline solution (success rate: 50.8%), with 39 (69.9%) of them
      adequate for analysis. Only two of the 26 patients produced adequate samples in
      the three consecutive evaluations, which impaired the determination of a
      potential association between sputum cellularity and FeNO levels throughout the
      study. In conclusion, among the parameters of this study, it was difficult to
      perform and to interpret the serial analysis of spontaneous or induced sputum.
      Serum interleukins, which remained at very low or undetectable levels in most
      patients, were not found to be useful for therapeutic monitoring, except for IL-5
      that seems to present some correlation with levels of FeNO exhaled. Monitoring of
      the mean FEV1 indicated no significant variations during the treatment,
      demonstrating that functional stability or the absence of obstruction may not
      reflect the adequate management of asthma. Serial measurement of FeNO seemed to
      best reflect the progressive anti-inflammatory action of ICS in asthma.

PMID- 18085695
TI  - Incidence of HHV7 in donors and recipients of allogeneic hematopoietic stem cell
      transplantation.

PMID- 18085696
TI  - Lung function and somatic growth in patients with hemoglobin SC sickle cell
      disease.
AB  - OBJECTIVE: To investigate the changes in lung function and somatic growth that
      occur over time in children with hemoglobin SC (Hb-SC) sickle cell disease (SCD).
      METHODS: Measurements of lung function and somatic growth were performed in
      patients with Hb-SC twice with an interval of 50.2 +/- 26.0 months. Comparisons
      were made with a group of patients with hemoglobin SS (Hb-SS) SCD, matched by
      age, race, and gender who underwent similar testing and served as controls.
      RESULTS: Indices of lung function in patients with Hb-SC were and remained within
      the normal range in the two testing periods and they were significantly higher
      than those measured among patients with Hb-SS. However, there was significant and
      similar decline (as percentage from baseline) over time in both groups (forced
      vital capacity, FVC: -3.7 +/- 9.4 vs. -3.8 +/- 14.2; forced expiratory volume in
      the first second, FEV1: -7.4 +/- 9.3 vs. -6.8 +/- 15.2; forced expiratory flow at
      25-75% of FVC, FEF(25-75): -13.7 +/- 20.6 vs. -12.1 +/- 24.7 for Hb-SC and Hb-SS
      respectively). The body mass index (BMI, percentile) was significantly (P < 0.05)
      higher among patients with Hb-SC (49 +/- 36 vs. 26 +/- 18) and increased over
      time in both groups (50 +/- 33 vs. 32 +/- 31). CONCLUSION: Lung function is
      generally normal among children with Hb-SC, but it declines over time in a
      fashion similar to that observed among patients with Hb-SS SCD. The decline is
      slow and it is not associated with changes in somatic growth. Our findings
      suggest that patients with Hb-SC should probably have the same close follow-up as
      patients with Hb-SS.

PMID- 18085694
TI  - Azithromycin does not improve disease course in hospitalized infants with
      respiratory syncytial virus (RSV) lower respiratory tract disease: a randomized
      equivalence trial.
AB  - BACKGROUND: Nearly half of all hospitalized infants with respiratory syncytial
      virus (RSV) lower respiratory tract disease (LRTD) are treated with (parenteral)
      antibiotics. The present study was designed to test our hypothesis that the use
      of antibiotics would not lead to a reduced duration of hospitalization in mild to
      moderate RSV LRTD. METHODS: Seventy-one patients < or =24 months of age with a
      virologically confirmed clinical diagnosis of RSV LRTD were randomized to
      azithromycin 10 mg/kg/day (n = 32) or placebo (n = 39) in a multicenter,
      randomized, double-blind, placebo-controlled equivalence trial during three RSV
      seasons (2002-2004 through 2005-2006). Primary endpoint was duration of
      hospitalization, secondary endpoints included duration of oxygen supplementation
      and nasogastric tube feeding, course of RSV symptom score, number of PICU
      referrals and number of patients who received additional antibiotic treatment.
      Data were analyzed according to the intention-to-treat principle using the Mann
      Whitney U-test or chi2 test considering P < 0.05 as statistically significant.
      RESULTS: Included patients were comparable with respect to baseline demographics,
      clinical characteristics, laboratory and roentgenologic investigations. The mean
      duration of hospitalization was not significantly different between patients
      treated with azithromycin or placebo (132.0 +/- 10.8 vs. 139.6 +/- 7.7 hr, P =
      0.328). Azithromycin was not associated with a stronger resolution of clinical
      symptoms represented by the RSV symptom score. Four patients were treated with
      antibiotics after 72 hr, three of them were assigned to placebo (P = 0.406).
      CONCLUSIONS: Infants and young children with RSV LRTD do not benefit from routine
      treatment with antibiotics (ISRCTN number 86554663).

PMID- 18085698
TI  - Effects of montelukast on subjective and objective outcome measures in preschool
      asthmatic children.
AB  - It is well accepted that control of airway inflammation is crucial for overall
      asthma control. Hence, efficient anti-inflammatory therapy is important for
      disease control. Therefore, we studied the effect of a treatment with montelukast
      on subjective and objective measures in preschool asthmatic children with
      insufficient control of airway inflammation, illustrated by increased fractional
      exhaled nitric oxide (FeNO). Thirty-one preschool children (2.5-5 years) were
      included in this study. Children with FeNO > or = 10 ppb at the first visit
      received montelukast 4 mg as a first line therapy or an add-on therapy to their
      baseline treatment (group 1). Therapy was not changed at first visit in children
      with FeNO < 10 ppb (group 2). Symptom scores, FeNO, lung function (forced
      oscillation, Rrs8Hz) and airway responsiveness to adenosine 5'-monophosphate
      (AMP) were assessed at visits 1 and 2 eight weeks apart. There was a significant
      decrease in FeNO (median [interquartile range]; 12.9 [3.7] vs. 7.6 [6.85] ppb, P
      = 0.011), Rrs8Hz (mean +/- SD; 10.03 +/- 3.1 vs. 8.72 +/- 2.43 hPa.s/L; P =
      0.047) and symptom scores (2[2] vs. 1.5[2], P = 0.034) and a significant increase
      in the provocative AMP dose (2.65 +/- 2.1 vs. 4.54 +/- 1.05; P = 0.015) in group
      1 but not in group 2. First line or add-on treatment of oral montelukast in
      preschool children with mild to moderate asthma and elevated FeNO, decreased
      levels of FeNO, improved airway responsiveness to AMP, lung function and symptom
      scores.

PMID- 18085699
TI  - Who will care for tomorrow's children with benign hematologic conditions? A
      comment.

PMID- 18085702
TI  - Anatomic basis of perforator flaps of medial vastus muscle.
AB  - The purpose of this study was to elucidate anatomical features of perforating
      branch flaps based on the muscular branches of the medial vastus muscle and to
      seek a new, applicable technique that could be used in repairing soft tissue
      defects around human knees. In this study, the origin, the course, the branches,
      the distribution, and the distal anastomosis of the muscular branch of the medial
      vastus muscle were observed in 30 sides of adult cadaveric lower limb specimens
      with the adductor tubercle, the patella midpoint, and the inguinal ligament
      midpoint as the observation markers. The specimens had been perfused arterially
      with red gelatin before they were supplied. It was observed that the femoral
      artery gave constant muscular branches into the medial vastus muscle at the tip
      of the femoral triangle. The artery entered the muscle via the hilum and ran
      laterally downwards along the muscular bundle until it reached the lateral
      patella to anastomose with the arterial circle around the bone. Along its course,
      it also gave 1-3 (1/77%) musculocutaneous perforating branches (0.5-0.9 mm in
      diameter). It then extended vertically through the medial vastus muscle into the
      deep fascia and ran superficially to the overlying skin of the muscle. A flap
      based on the perforating branch of the medial vastus muscle could be harvested at
      a size of about 8.5 cm x 15.0 cm and might be transferred retrograde to repair
      the soft tissue defect around the knee.

PMID- 18085703
TI  - Proliferation and neurogenesis of neural stem cells enhanced by cerebral
      microvascular endothelial cells.
AB  - In adult mammalian brain, vascular cells reside throughout life, close to central
      nervous system germinal zones, and neural stem cells (NSCs) mainly localize in
      the dentate gyrus of the hippocampus, subventricular zone, and olfactory bulb.
      Microvessels appear to produce a special microenvironment that may influence the
      characteristics of NSCs. To explore this potential correlation, an in vitro model
      with cocultured cerebral microvascular endothelial cells (CMECs) and NSCs was
      established in our study by using a transwell coculture system. The expression of
      nestin and NF in the early stage of coculture, and NF in the late stage, was
      detected by immunostaining. The results demonstrated that CMECs can stimulate
      self-renewal of NSCs and inhibit their differentiation, implying the potential of
      CMECs in promoting the neural differentiation of NSCs.

PMID- 18085705
TI  - Introduction to the Chinese Society issue.

PMID- 18085704
TI  - Effect of hydraulic dilation on changes of caliber and thickness in vascular
      vessel: an experimental study.
AB  - OBJECTIVE: To study the proliferation of artery after hydraulic dilation under
      different pressures. MATERIAL AND METHODS: Right carotid arteries of New Zealand
      white rabbits (group A, B, C, D) were dilated by hydraulic dilation under
      different pressures (0, 40, 80, 120 Kpa). The arterial caliber, thickness of
      tunica intima (TI) and smooth muscle (SM) were measured with TJTY-300 automatic
      medical photograph analyzer at 0, 1, 2 weeks, respectively after dilation.
      RESULTS: 1) The arterial caliber of group B was greater than that in group A (P <
      0.05, P < 0.01) at 0 and 1 week after hydraulic dilation, but no difference was
      found in 2 weeks after dilation. The thickness of TI and SM of group B was not
      different from group A at every time point. 2) The arterial calibers of group C,
      D were significantly larger than that of group A immediately and at 1 week (P <
      0.01, P < 0.01). Group B, D showed no difference with group A (P > 0.05) at 2
      weeks. The thickness of TI and SM of group C, D had no difference with group A (P
      > 0.05) immediately, but greater than group A at 1 and 2 weeks (P < 0.01, P <
      0.01). CONCLUSION: 1) Arterial caliber can be increased by hydraulic dilation
      under different pressures. But hydraulic dilation over 80 Kpa pressure may lead
      to proliferation of TI and SM. 2) It is safe for arterial hydraulic dilation to
      be conducted under pressure of 40 Kpa.

PMID- 18085706
TI  - A reversed superficial peroneal neurocutaneous island flap based on the
      descending branch of the distal peroneal perforator: clinical experiences and
      modifications.
AB  - The distally based neurocutaneous flaps have been popular for lower leg and foot
      reconstruction. On the basis of pre-existing anatomic studies and clinical
      experiences, we designed a reversed superficial peroneal neurocutaneous island
      flap with the descending branch of the distal peroneal perforator as the pedicle.
      The flap is supplied through both axial perforator and longitudinal chain-linked
      vascular plexuses. This modified neurocutaneous island flap, measuring around 5
      cm x 4 cm to 12 cm x 13 cm in size, was transferred for coverage of foot soft
      tissue defects in 21 cases with a low complication rate. Compared to the original
      neurocutaneous flap, the rotation point of this flap is more distal and the
      pedicle is thinner. It could provide good texture and contour matching to the
      recipient area. In conclusion, the modified neurocutaneous island flap provides a
      reliable tool for repairing soft-tissue defects of the ankle and foot.

PMID- 18085707
TI  - Peroxisome proliferator-activated receptor-gamma protects against hepatic
      ischemia/reperfusion injury in mice.
AB  - The function of peroxisome proliferator-activated receptor-gamma (PPARgamma) in
      hepatic inflammation and injury is unclear. In this study, we sought to determine
      the role of PPARgamma in hepatic ischemia/reperfusion injury in mice. Male mice
      were subjected to 90 minutes of partial hepatic ischemia followed by up to 8
      hours of reperfusion. PPARgamma was found to be constitutively activated in
      hepatocytes but not in nonparenchymal cells. Upon induction of ischemia, hepatic
      PPARgamma activation rapidly decreased and remained suppressed throughout the 8
      hour reperfusion period. This reduced activation was not a result of decreased
      protein availability as hepatic nuclear PPARgamma, retinoid X receptor-alpha
      (RXRalpha), and PPARgamma/RXRalpha heterodimer expression was maintained.
      Accompanying the decrease in PPARgamma activation was a decrease in the
      expression of the natural ligand 15-deoxy-Delta(12,14)-prostaglandin J(2). This
      was associated with reduced interaction of PPARgamma and the coactivator, p300.
      To determine whether PPARgamma activation is hepatoprotective during hepatic
      ischemia/reperfusion injury, mice were treated with the PPARgamma agonists,
      rosiglitazone and connecting peptide. These treatments increased PPARgamma
      activation and reduced liver injury compared to untreated mice. Furthermore,
      PPARgamma-deficient mice had more liver injury after ischemia/reperfusion than
      their wild-type counterparts. CONCLUSION: These data suggest that PPARgamma is an
      important endogenous regulator of, and potential therapeutic target for, ischemic
      liver injury.

PMID- 18085708
TI  - Hepatitis C virus receptor expression in normal and diseased liver tissue.
AB  - The principal site of hepatitis C virus (HCV) replication is the liver. HCV
      pseudoparticles infect human liver derived cell lines and this suggests that
      liver-specific receptors contribute to defining HCV hepatotropism. At least three
      host cell molecules have been reported to be important for HCV entry: the
      tetraspanin CD81, scavenger receptor class B member I (SR-BI), and the tight
      junction (TJ) protein Claudin 1 (CLDN1). Hepatocytes in liver tissue coexpress
      CD81, SR-BI, and CLDN1, consistent with their ability to support HCV entry. CLDN1
      localized at the apical-canalicular TJ region and at basolateral-sinusoidal
      hepatocyte surfaces in normal tissue and colocalized with CD81 at both sites. In
      contrast, CLDN1 appeared to colocalize with SR-BI at the basolateral-sinusoidal
      surface. CLDN1 expression was increased on basolateral hepatocyte membranes in
      HCV-infected and other chronically inflamed liver tissue compared with normal
      liver. In contrast, CLDN4 hepatocellular staining was comparable in normal and
      diseased liver tissue. CONCLUSION: HCV infection of Huh-7.5 hepatoma cells in
      vitro significantly increased CLDN1 expression levels, consistent with a direct
      modulation of CLDN1 by virus infection. In HCV infected livers,
      immunohistochemical studies revealed focal patterns of CLDN1 staining, suggesting
      localized areas of increased CLDN1 expression in vivo which may potentiate local
      viral spread within the liver.

PMID- 18085709
TI  - Post-neonatal drop in alveolar SP-A expression: biological significance for
      increased vulnerability to SIDS?
AB  - BACKGROUND: Surfactant protein A (SP-A) is synthesized in the lung and is a part
      of the innate immune system. The aim of this study was to evaluate the expression
      of SP-A in lung tissue from fetuses, infants, children and adults with special
      regard to sudden infant death syndrome (SIDS). METHODS: A total of 160 cases were
      studied; 19 fetuses and neonates, 59 SIDS and 49 explained infant deaths below 1
      year of age, 19 toddlers and 14 adults. Immunohistochemical detection of SP-A
      using monoclonal antibodies was performed by microscopy of lung tissue specimens
      collected at autopsy. A scoring system was developed enabling semi-quantitative
      estimation of staining intensity and distribution. RESULTS: SP-A was detected in
      the terminal bronchioles and alveolar spaces of fetuses >35 weeks gestation. The
      intra-alveolar SP-A expression increased in the perinatal period followed by a
      marked drop in infants aged between 1 week and 5 months. Infants aged >5 months
      had abundant SP-A expression corresponding to older children and adults. There
      was no difference in the age distribution between cases of SIDS and explained
      deaths. CONCLUSIONS: The apparent drop in SP-A expression takes place in the
      first months after birth, corresponding with the classical age peak of SIDS. We
      therefore hypothesize that low expression of SP-A may be related in some as-yet
      undetermined way to the increased risk of SIDS at that age.

PMID- 18085710
TI  - Prophylaxis against respiratory syncytial virus in young children with cystic
      fibrosis.
AB  - INTRODUCTION: In cystic fibrosis (CF) patients, respiratory syncytial virus (RSV)
      infection is associated with significant morbidity. Although passive prophylaxis
      with palivizumab lowers hospitalization rate for RSV infection in populations at
      risk of severe infection, its use is not recommended in infants with CF disease.
      OBJECTIVE: To determine the effect of palivizumab prophylaxis on hospitalization
      for acute respiratory illness in young children with CF during the first RSV
      season following the diagnosis of CF. METHODS: In this retrospective study,
      medical records of patients diagnosed with CF between the years 1997 and 2005
      inclusively and on whom the diagnosis was made before 18 months of age were
      reviewed. Collected data included age at diagnosis, palivizumab prophylaxis,
      occurrence of hospitalization for acute respiratory tract illness during the RSV
      season and identification of RSV infection. RESULTS: A diagnosis of CF was made
      in 76 young children and data collected from 75 children. Of those, 40 did not
      receive RSV prophylaxis while 35 received palivizumab injection monthly during
      the RSV season. Among non-recipient children, 7 out of 40 were hospitalized for
      acute respiratory illness during the RSV season. Of these seven patients, RSV
      detection was positive in nasopharyngeal secretions in three patients, negative
      in one patient and not requested in the others. Among palivizumab recipients, 3
      out of 35 children were hospitalized for acute respiratory illness (P > 0.05
      compared to non-recipients group). In these three palivizumab recipients, RSV
      detection was negative in nasopharyngeal secretions. Palivizumab recipients
      experienced fewer hospital days per patient for acute respiratory illness (mean
      +/- SD: 0.8 +/- 3.07 days) as compared to non-recipients (mean +/- SD: 1.73 +/-
      4.27 days) but this difference did not reach statistical significance.
      CONCLUSION: CF infants may benefit from RSV immunoprophylaxis with palivizumab.

PMID- 18085711
TI  - Polymorph transitions of bicalutamide: a remarkable example of mechanical
      activation.
AB  - Bicalutamide, an active pharmaceutical ingredient possessing antiandrogenic
      activity, is known to exhibit polymorphism. The higher melting Form I relates
      monotropically to the lower melting Form II. The amorphous form can be easily
      produced by quench cooling the melt, but it is known to crystallize spontaneously
      to Form II at room temperature within days. Our results show that crystallization
      of amorphous bicalutamide is greatly influenced by experimental conditions and
      sample treatment. The effect of mechanical activation on the polymorph
      transitions is investigated in detail. Seeds of Form I can be formed in the
      amorphous phase even due to gentle mechanical treatment, which results in
      crystallization to the more stable structure at elevated temperature. The
      crystalline Form II may as well be transformed to the stable modification through
      mechanical activation at elevated temperature.

PMID- 18085712
TI  - Drug release phenomena within a hydrophobic starch acetate matrix: FTIR mapping
      of tablets after in vitro dissolution testing.
AB  - The aim of this study was to assess the utility of Fourier transform infrared
      mapping to study the drug release phenomena within a hydrophobic matrix tablet.
      Starch acetate with a degree of substitution (2.7) was used as a hydrophobic
      matrix former. Anhydrous caffeine and riboflavin sodium phosphate were used as
      water soluble model drugs. The USP (XXVIII) paddle-method was selected as an in
      vitro dissolution test. Mapping of the diluted tablets' cross-section was
      performed by attenuated total reflection mode. Fourier transform infrared mapping
      can distinguish drug particles from the bulk matrix and it can be considered as a
      valuable method for obtaining both quantitative and qualitative information on
      drug release processes. The physicochemical properties of the drug compound
      strongly contribute to its release behavior when the USP paddle in vitro
      dissolution test is used. Mapping of the riboflavin product revealed a more
      homogenous matrix distribution due to its smaller particle size. Consequently,
      its dissolution release profile was more uniform than caffeine which possessed a
      wider particle size distribution and lower solubility. Mapping showed that
      caffeine became localized in the lower part of the tablet unlike riboflavin. The
      hydrodynamic conditions during the in vitro release test might contribute to this
      differentiation.

PMID- 18085713
TI  - Multivariate chemometric approach to thermal solid-state FT-IR monitoring of
      pharmaceutical drug compound.
AB  - The study of thermal-related solid-state reaction monitored by spectroscopic
      method needs the use of advanced multivariate chemometric approach. It is because
      visual inspection of spectral data on particular functional groups or spectral
      bands is difficult to reveal the complete physical and chemical information. The
      spectral contributions from various species involved in the solid-state changes
      are generally highly overlapping and the spectral differences between reactant
      and product are usually quite minute. In this article, we demonstrate the use of
      multivariate chemometric approach to resolve the in situ thermal-dependent
      Fourier-transform infrared (FT-IR) mixture spectra of lisinopril dihydrate when
      it was heated from 24 to 170 degrees C. The collected FT-IR mixture spectra were
      first subjected to singular value decomposition (SVD) to obtain the right
      singular vectors. The right singular vectors were rotated into a set of pure
      component spectral estimates based on entropy minimization and spectral
      dissimilarity objective functions. The resulting pure component spectral
      estimates were then further refined using alternating least squares (ALS). In
      current study, four pure component spectra, that is, lisinopril dihydrate,
      monohydrate, anhydrate, and diketopiperazine (DKP) were all resolved and the
      relative thermal-dependent contributions of each component were also obtained.
      These relative contributions revealed the critical temperature for each
      transformation and degradation. This novel approach provides better
      interpretation of the pathway of dehydration and intramolecular cyclization of
      lisinopril dihydrate in the solid state. In addition, it can be used to
      complement the information obtained from differential scanning calorimetry (DSC)
      and thermogravimetric analysis (TGA).

PMID- 18085714
TI  - Effect of muscle-fiber velocity recovery function on motor unit action potential
      properties in voluntary contractions.
AB  - Measurements of muscle-fiber conduction velocity during voluntary contractions
      have been used in the diagnosis of neuromuscular diseases. However, the velocity
      of propagation of action potentials depends on the interspike interval of
      activation due to the velocity recovery function (VRF) of muscle fibers. The
      comparison of muscle-fiber conduction velocity estimates between individuals may
      thus be influenced by differences in motor unit discharge rate. This study
      investigates action potential properties of motor units of the
      sternocleidomastoid muscle during voluntary modulation of discharge rate with the
      purpose of assessing the effect of the VRF on motor unit properties in voluntary
      contractions. Nineteen healthy men trained to control a target motor unit with
      feedback of surface multichannel electromyographic (EMG) signals. The subjects
      performed three 30-s contractions of cervical flexion/rotation modulating the
      discharge rate of the target motor unit from 6.6 +/- 1.6 pps to 28.0 +/- 6.4 pps.
      Action potential conduction velocity was correlated to instantaneous discharge
      rate (R = 0.38 +/- 0.21). Action potential conduction velocity, peak-to-peak
      amplitude, and duration varied between minimum and maximum discharge rate (P <
      0.01; percent change 12.3 +/- 5.0, -11.8 +/- 9.9, and -12.9 +/- 7.3). Thus, the
      properties of surface motor unit action potentials vary with modulation of
      discharge rate. This has implications for the use of conduction velocity values
      measured during voluntary contractions to differentiate patient populations from
      healthy individuals and for the development of normative data.

PMID- 18085715
TI  - Congenital diaphragm weakness without neuromuscular disease.
AB  - We report on two children presenting at birth with respiratory failure, bilateral
      diaphragmatic eventration, and floppiness. Electrodiagnostic studies of the
      limbs, and biochemical and DNA studies excluded generalized neuromuscular
      diseases. Phrenic nerve electrodiagnostic studies and electromyography of the
      diaphragm suggested isolated diaphragm hypoplasia. Diaphragm muscle biopsy showed
      a paucity of muscle fibers. Isolated hypoplasia of the diaphragm is a rare cause
      of neonatal respiratory failure, which may have a favorable outcome with long
      term ventilatory support.

PMID- 18085719
TI  - Aggregation and membrane permeabilizing properties of designed histidine
      containing cationic linear peptide antibiotics.
AB  - Members of the LAH4 family of cationic linear peptide antibiotics have been
      designed to form amphipathic helical structures in membrane environments and
      switch from alignments parallel to the bilayer surface to transmembrane
      orientations in a pH-dependent manner. Here the aggregation in aqueous buffer of
      two members of the family has been investigated by DLS. The peptides form
      monomers or small oligomers at pH = 5 but associate into nano-sized aggregates at
      physiological pH. The diameter of these latter complexes can be considerably
      reduced by sonication. Furthermore, the membrane interactions of the various
      supramolecular aggregates with POPC or mixed POPC/POPS vesicles have been
      investigated in calcein-release assays. In all the cases tested, the large
      preformed oligomeric peptide aggregates of 20-40 nm in size were more active than
      the structures with the smallest hydrodynamic radii in releasing the fluorescent
      dye from LUV. In contrast, the relative activity after sonication depends on the
      specific environment tested. The data suggest that these amphiphiles form
      micellar structures and support the notion that they can act in a manner
      comparable to detergents.

PMID- 18085720
TI  - The role of peptides in blood-brain barrier nanotechnology.
AB  - The blood-brain barrier (BBB) regulates the passage of molecules between the
      bloodstream and the brain. Overcoming the difficulty of delivery drugs to
      specific areas of the brain is a major challenge. The BBB exerts a
      neuroprotective function as it hinders the delivery of diagnostic and therapeutic
      agents to the brain. Here, we provide an overview of the way in which peptides
      and nanotechnology are being exploited in tandem to address this problem.
      Peptides can be used as specialised coatings able to transport nanoparticles with
      specific properties, such as targeting. The nanoparticle can also carry a peptide
      drug. Furthermore, peptides can be used in less conventional approaches such as
      all-peptide nanoparticles. In summary, the combined use of peptides and
      nanotechnology offers tremendous hope in the treatment of brain disorders.

PMID- 18085721
TI  - Adenoviral vector-mediated glucagon-like peptide 1 gene therapy improves glucose
      homeostasis in Zucker diabetic fatty rats.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone
      that plays an important role in glucose homeostasis. Its functions include
      glucose-stimulated insulin secretion, suppression of glucagon secretion,
      deceleration of gastric emptying, and reduction in appetite and food intake.
      Despite the numerous antidiabetic properties of GLP-1, its therapeutic potential
      is limited by its short biological half-life due to rapid enzymatic degradation
      by dipeptidyl peptidase IV. The present study aimed to demonstrate the
      therapeutic effects of constitutively expressed GLP-1 in an overt type 2 diabetic
      animal model using an adenoviral vector system. METHODS: A novel plasmid (pAAV
      ILGLP-1) and recombinant adenoviral vector (Ad-ILGLP-1) were constructed with the
      cytomegalovirus promoter and insulin leader sequence followed by GLP-1(7-37)
      cDNA. RESULTS: The results of an enzyme-linked immunosorbent assay showed
      significantly elevated levels of GLP-1(7-37) secreted by human embryonic kidney
      cells transfected with the construct containing the leader sequence. A single
      intravenous administration of Ad-ILGLP-1 into 12-week-old Zucker diabetic fatty
      (ZDF) rats, which have overt type 2 diabetes mellitus (T2DM), achieved near
      normoglycemia for 3 weeks and improved utilization of blood glucose in glucose
      tolerance tests. Circulating plasma levels of GLP-1 increased in GLP-1-treated
      ZDF rats, but diminished 21 days after treatment. When compared with controls, Ad
      ILGLP-1-treated ZDF rats had a lower homeostasis model assessment for insulin
      resistance score indicating amelioration in insulin resistance.
      Immunohistochemical staining showed that cells expressing GLP-1 were found in the
      livers of GLP-1-treated ZDF rats. CONCLUSIONS: These data suggest that GLP-1 gene
      therapy can improve glucose homeostasis in fully developed diabetic animal models
      and may be a promising treatment modality for T2DM in humans.

PMID- 18085722
TI  - Molecular machines working on surfaces and at interfaces.
AB  - In the past ten years a great variety of artificial molecular machines have been
      constructed, and very interesting concepts for controlling molecular-level
      movements by external inputs have been developed. Most of the studies, however,
      have been performed in solution, where the investigated systems contain a huge
      number of molecules which behave independently from one another because they
      cannot be addressed individually. Before such systems can find applications in
      many fields of technology, they must be interfaced with the macroscopic world by
      ordering them in some way so that they can behave coherently and can be addressed
      in space. The problem of obtaining ordered arrays of molecular machines can be
      addressed by a variety of techniques, which include deposition on surfaces,
      incorporation into polymers, organization at interfaces, and immobilization in
      membranes or porous materials. In the last few years, the development of scanning
      probe techniques has also enabled direct observation and manipulation of single
      molecular-machine molecules on surfaces. Techniques of this kind have opened
      novel routes to the study of molecular machines, and have also contributed to
      better understanding the differences between movement at the macroscopic and
      molecular levels. This paper reviews some recent achievements in the field of
      molecular machines working on surfaces and at interfaces, as single molecules or
      ordered arrays. Hybrid natural-artificial machines are also discussed, and the
      working mechanism of some natural machines is illustrated for the purpose of
      comparison.

PMID- 18085723
TI  - Microfluidic pump powered by self-organizing bacteria.
AB  - Results are presented that demonstrate the successful use of live bacteria as
      mechanical actuators in microfabricated fluid systems. The flow deposition of
      bacteria is used to create a motile bacterial carpet that can generate local
      fluid motion inside a microfabricated system. By tracking the motion of tracer
      particles, we demonstrate that the bacterial cells that comprise the carpet self
      organize, generating a collective fluid motion that can pump fluid autonomously
      through a microfabricated channel at speeds as high as 25 microm s(-1). The
      pumping performance of the system can also be augmented by changing the chemical
      environment. The addition of glucose to the working buffer raises the metabolic
      activity of the bacterial carpet, resulting in increased pumping performance. The
      performance of the bacterial pump is also shown to be strongly influenced by the
      global geometry of the pump, with narrower channels achieving a higher pumping
      velocity with a faster rise time.

PMID- 18085725
TI  - Biodistribution and expression of targeted fusion anti-caries DNA vaccine pGJA
      P/VAX in mice.
AB  - OBJECTIVE: To study the biodistribution and expression of anti-caries DNA vaccine
      pGJA-P/VAX in mice models following intranasal (i.n.) and intramuscular (i.m.)
      immunization. METHODS: pGJA-P/VAX and pVAX1 were administrated i.n. and i.m. to
      mice, respectively. Blood and organs were harvested and then genomic DNA was
      extracted. mRNA in the original tissues and draining lymph nodes was isolated.
      The in vivo fate of plasmid DNA in these samples was evaluated with real-time
      quantitative polymerase chain reaction (PCR). RESULTS: The ratio of the area
      under the curve (AUC) and maximum concentration (Cmax) after i.n. immunization
      were higher than that after i.m. injection. At 1 day post i.n. immunization, the
      localization of plasmid to the heart, spleen and lung was notable compared with
      that to the nasal mucosa. At 2 days, for i.n. immunization, the concentration
      value of plasmid in the mucosa-associated lymphoid tissues such as lung, kidney
      and gastrointestine had increased and was greater than that via i.m. injection.
      At later time points, the plasmid was primarily in the original tissues and
      draining lymph nodes. mRNA expression was observed in the topical tissues up to 7
      days and in the draining lymph nodes for at least 3 days. CONCLUSIONS: These
      results indicate that the distribution of pGJA-P/VAX was widespread in vivo, and
      the expression was significant in the inoculation tissue and draining lymph nodes
      after i.n. immunization and i.m. injection. This data provides evidence which
      supports the long-term immune responses and the basis of further research on
      safety issues.

PMID- 18085726
TI  - Intravenous glial-derived neurotrophic factor gene therapy of experimental
      Parkinson's disease with Trojan horse liposomes and a tyrosine hydroxylase
      promoter.
AB  - BACKGROUND: Rats with experimental Parkinson's disease (PD) are treated with
      intravenous glial-derived neurotrophic factor (GDNF) plasmid DNA, non-viral gene
      therapy using Trojan horse liposomes (THLs) targeted with a monoclonal antibody
      (MAb) to the rat transferrin receptor (TfR). Expression of the transgene is
      confined to catecholaminergic cells by placement of the GDNF gene under the
      influence of the rat tyrosine hydroxylase (TH) promoter. METHODS: A 13-kb
      eukaryotic expression plasmid, designated pTHpro-GDNF, is engineered in which the
      human prepro GDNF cDNA is driven by 8 kb of the 5'-flanking sequence of the rat
      TH promoter (pro), and is 3'-flanked by the bovine growth hormone transcription
      termination sequence. The pTHpro-GDNF plasmid DNA is encapsulated in THLs
      targeted with a TfRMAb, and a single intravenous injection is given to rats at 2
      weeks after experimental PD is induced by intra-cerebral 6-hydroxydopamine.
      RESULTS: Expression of the GDNF gene, under the influence of the TH promoter, is
      restricted compared to GDNF expression under the influence of the cytomegalovirus
      promoter. GDNF is elevated only in organs of the rat where TH gene expression is
      observed, including the substantia nigra, liver and adrenal gland. The single,
      delayed intravenous administration of the GDNF gene therapy causes a lasting
      reduction in apormorphine-induced rotation, which is correlated with a 19-fold
      increase in striatal TH enzyme activity. Both dose-response and time-responses
      are observed. CONCLUSIONS: Sustained therapeutic effects are achieved in
      experimental PD with a delayed single intravenous dosing of GDNF plasmid DNA gene
      therapy, using receptor-targeted THLs and a region-specific promoter.

PMID- 18085728
TI  - Evaluation of the presentation of systemic onset juvenile rheumatoid arthritis:
      data from the Pennsylvania Systemic Onset Juvenile Arthritis Registry (PASOJAR).
AB  - OBJECTIVE: To characterize the initial clinical and laboratory features of
      patients with systemic onset juvenile rheumatoid arthritis (soJRA) through a Web
      based registry. METHODS: Patients diagnosed with soJRA in the last 15 years at 3
      medical centers in Pennsylvania were identified. Data were collected
      retrospectively using a Web-based interface in compliance with patient privacy
      standards. Inferential statistics were used to compare features of patients with
      and without macrophage activation syndrome. RESULTS: We identified 136 patients;
      88% of patients presented with arthritis (8% mono-, 45% oligo-, 47%
      polyarticular). The most common joints involved were the knee (68% of patients
      with arthritis), wrist (68%), and ankle (57%). The International League of
      Associations for Rheumatology criteria for systemic juvenile idiopathic arthritis
      (SJIA) identified only 30% of patients at presentation. CONCLUSION: We
      successfully characterized the presenting features of a relatively rare disease,
      soJRA, through the use of a Web-based registry. Current classification criteria
      for SJIA may not be particularly sensitive for diagnosis at presentation.

PMID- 18085729
TI  - Paraneoplastic vasculitis in patients with solid tumors: report of 15 cases.
AB  - OBJECTIVE: To review all cases of concurrent vasculitis and solid tumors
      diagnosed at our Department over a 15-year period and explore evidence that would
      support the notion of vasculitis being a true paraneoplastic syndrome. METHODS:
      We reviewed the records of all patients diagnosed with vasculitis and solid
      tumors within 12 months of each other and prospectively followed until death or
      our report. We analyzed the main features and outcome of vasculitis in this
      setting. We also reviewed all cases published in the French-English literature.
      RESULTS: Fifteen patients (9 men and 6 women) in whom both vasculitis and solid
      tumor occurred within the same 12 months were identified. Mean age was 72.5 years
      (range 58-84). In 7 cases the diagnosis of vasculitis antedated that of cancer,
      in 6 both processes were synchronously diagnosed, and in 2 vasculitis appeared
      after cancer diagnosis. The most common vasculitis was cutaneous leukocytoclastic
      vasculitis (n = 9). Other vasculitides included Henoch-Shonlein purpura (n = 2),
      polyarteritis nodosa (n = 1), and giant cell arteritis (n = 3). The commonest
      malignancies were carcinomas of urinary organs (40%), lung (26.7%), and
      gastrointestinal tract (26.7%). The median followup was 28.4 months (range 1-96).
      Thirteen of the 15 patients demonstrated concordance of disease activity and
      treatment response for both cancer and vasculitis. Vasculitis flared heralding
      tumor recurrence or progression in 7 (46.6%) cases. CONCLUSION: In our patients,
      resolution of vasculitis following effective treatment of the putatively linked
      malignancy, and recurrence of vasculitis heralding tumor recurrence or
      progression, provide strong evidence for vasculitis being a true paraneoplastic
      syndrome. Chronic or persistent vasculitis with poor response to usually
      effective therapy, especially in elderly patients, should raise questions about
      underlying malignancy.

PMID- 18085730
TI  - Relapses in patients with antineutrophil cytoplasmic autoantibody-associated
      vasculitis: likely to begin with the same organ as initial onset.
AB  - OBJECTIVE: In antineutrophil cytoplasmic antibody-associated vasculitis (AAV),
      relapses constitute a challenge despite initial good control. Our objective was
      to investigate whether patients with relapses shared the same initial organ
      involvement. METHODS: One hundred sixty patients with AAV in our center were
      investigated. Of these 160, 38 experienced relapse during followup. Clinical and
      laboratory data were analyzed. RESULTS: Among the 38 patients, there was a total
      of 55 relapse events, 39 (70.9%) of which had the same initial organ as in the
      initial onset. CONCLUSION: Relapses in AAV were likely to begin with the same
      organ as in the initial onset; this facilitates early recognition of relapses.

PMID- 18085731
TI  - High-resolution computed tomography characterization of interstitial lung
      diseases in polymyositis/dermatomyositis.
AB  - OBJECTIVE: Interstitial lung disease (ILD) associated with polymyositis (PM) and
      dermatomyositis (DM) sometimes progresses rapidly and is resistant to therapy.
      Clinical features that forecast the prognosis of the disease remain to be
      elucidated. Our aim was to assess if selected clinical features and high
      resolution computed tomography (HRCT) findings can assist in predicting the
      clinical course of ILD in PM/DM. METHODS: We examined HRCT findings
      retrospectively for ILD identified in 17 patients with PM and 16 with DM.
      Radiological patterns and clinical features are analyzed in comparison with
      clinical course. RESULTS: Mortality rates were 12% and 44% for ILD associated
      with PM and DM, respectively. Most patients with DM died of rapidly progressive
      lung deterioration. No patient in the PM group died of respiratory failure. In
      the DM group, all patients with fatal ILD had ground-glass attenuation and
      reticular opacity as the principal radiological findings. Consolidation was
      recognized frequently as the principal pattern in nonfatal cases. Radiological
      patterns were categorized into 3 groups; A: consolidation dominant, B: ground
      glass attenuation/reticular opacity dominant without chronic fibrosing process,
      and C: ground-glass attenuation/reticular opacity dominant with chronic fibrosing
      process. Occurrences of fatal disease were 0%, 83%, and 20%, in groups A, B, and
      C. CONCLUSION: The prognosis of ILD associated with DM differs from that with PM.
      The former can be classified into 3 subgroups on the basis of radiological
      findings, which are closely associated with clinical course.

PMID- 18085732
TI  - Early intervention with corticosteroids and cyclosporin A and 2-hour postdose
      blood concentration monitoring improves the prognosis of acute/subacute
      interstitial pneumonia in dermatomyositis.
AB  - OBJECTIVE: We retrospectively examined the effect of combination therapy with
      prednisolone and cyclosporin A (CSA) for dermatomyositis (DM) presenting with
      acute/subacute interstitial pneumonia (A/SIP), the daily CSA dose, and the time
      from diagnosis of A/SIP to initiation of CSA treatment. METHODS: Subjects were 16
      DM patients with A/SIP. Seven patients were treated initially with 1 mg/kg/day
      prednisolone. When IP was progressive, CSA was added (Group A). Nine patients
      were treated initially with 1 mg/kg/day prednisolone and 4 mg/kg/day CSA, and 2-h
      postdose blood concentration (C2) monitoring was used to maintain the serum CSA
      level at 1000 ng/ml (Group B). RESULTS: Four of 7 patients in Group A (57%) and 1
      of 9 patients in Group B (11%) died of respiratory failure related to IP (p =
      0.06). Combination therapy with prednisolone and CSA at >or= 200 mg/day initiated
      within 15 days of diagnosis was effective for treatment of DM-A/SIP. The trough
      level (C0) and daily CSA dose were higher in Group B (201.3 ng/ml and 200.0
      mg/day, respectively) than in Group A (140.0 ng/ml and 166.4 mg/day). CSA was
      continued in all patients without severe side effects. No patient died of
      infection. CONCLUSION: Combination therapy of corticosteroids and CSA should be
      initiated during the early stage of IP. The daily CSA dose should also be
      controlled with measurement of serum CSA concentration to achieve maximal
      immunosuppressive effect. C2 monitoring is a useful tool for this control.

PMID- 18085733
TI  - Prevalence of ankylosing spondylitis and related spondyloarthritides in an urban
      area of Izmir, Turkey.
AB  - OBJECTIVE: To determine the prevalence of ankylosing spondylitis (AS) and related
      spondyloarthritides (SpA) in an adult urban population of Izmir, Turkey. METHODS:
      A survey was conducted of 2887 subjects aged 20 years or over, selected by
      cluster sampling. Those who responded positively to the screening questions were
      contacted by 2 rheumatologists and evaluated in detail to establish presence of
      AS (modified New York criteria) or related SpA (ESSG criteria). RESULTS: In the
      initial screening, 2835 subjects participated; 422 were considered screening
      positive and a telephone interview was done with 328 (78%). Based on their
      clinical history, 145 subjects were invited to the hospital and 120 (83%) agreed
      to do so. After detailed evaluation, 31 subjects were classified as having SpA
      (including 14 with AS). The age- and sex-adjusted prevalence was estimated to be
      0.49% for AS (95% CI 0.26-0.85), and 1.05% for SpA (95% CI 0.70-1.50). The
      prevalence of AS was 0.54% in men (95% CI 0.19-1.20) and 0.44% in women (95% CI
      0.19-0.88), and that of SpA was 0.88% in men (95% CI 0.42-1.59) and 1.22% in
      women (95% CI 0.73-1.89). CONCLUSION: This epidemiological study suggests a high
      prevalence (0.49%) of AS in an adult urban population from western Turkey, which
      equals that of rheumatoid arthritis in the same population. The overall
      prevalence of SpA, including AS, was 1.05%. A minimal male predominance was noted
      among AS patients, which disappeared among the whole group of patients with SpA.

PMID- 18085734
TI  - Renal involvement and followup of 130 patients with primary Sjogren's syndrome.
AB  - OBJECTIVE: To identify the clinical characteristics, pathological changes, and
      outcome of patients with primary Sjogren's syndrome (pSS). METHODS: All patients
      with pSS and renal involvement who were admitted to Ruijin Hospital from April
      1993 to December 2006 were included. All the data of clinical features and
      pathological changes were retrospectively analyzed. Forty-one patients underwent
      renal biopsies. RESULTS Our study included 130 patients with pSS: 122 women and 8
      men. Ages ranged from 16 to 68 years (mean 44.1 +/- 11.52). Ninety-five patients
      (73.1%) developed renal tubular acidosis (RTA); 91 were found to have distal RTA.
      Nine patients presented with hypokalemic paralysis. Four patients developed
      Fanconi syndrome and 3 were proved to have nephrogenic diabetes insipidus. Twenty
      seven of 130 patients (20.8%) developed tubular proteinuria and 18/130 (13.8%)
      presented glomerular involvement. Thirty-five patients (27.7%) developed renal
      failure (serum creatinine > 115 micromol/l). Most patients (70.8%) had increased
      serum IgG levels. The incidence of chronic interstitial nephritis was 80.5% among
      all the biopsy materials. Immunofluorescent staining was negative in most renal
      tissue. Ninety-six patients were treated with corticosteroids and/or
      immunosuppressant. Eighteen recovered renal function. CONCLUSION: Patients with
      pSS commonly present with renal impairment, mainly from renal tubular
      dysfunction. The combination of corticosteroids and immunosuppressors
      significantly improves the renal function of patients with pSS. There is a
      correlation between hypergammaglobulinemia and distal RTA. The renal
      acidification capacity for patients with hypergammaglobulinemia. should be
      monitored.

PMID- 18085735
TI  - Reappraisal of the effectiveness of methotrexate in psoriatic arthritis: results
      from a longitudinal observational cohort.
AB  - OBJECTIVE: In a previous study in our clinic, methotrexate (MTX) conferred no
      advantage with respect to clinical response or progression of damage after 24
      months in patients with psoriatic arthritis (PsA). Our aim was to determine if
      MTX is being used earlier in the course of PsA and in a higher dose and whether
      that has led to improved outcomes. METHODS: All patients treated with MTX for at
      least 24 months in our clinic, between 1994 and 2004, were included in the study.
      The outcome measures were the progression of radiographic peripheral joint damage
      score and a > or = 40% reduction in the number of actively inflamed joints. The
      data from our study were compared to those obtained from our previous study.
      RESULTS: Fifty-nine patients (36 men) treated with MTX for 24 months were
      identified. The mean age was 46 years, PsA duration 8 years, and active joint
      count 12.1 (4.6 swollen). The mean increase in radiographic damage score was 1.5.
      Sixty-eight percent of patients demonstrated improvement at 24 months. When
      compared to our previous study, there was a trend for MTX to be used earlier, at
      a higher dose, with greater clinical improvement and less progression of damage.
      CONCLUSION: Our study suggests that treatment with MTX has changed in the past
      decade to include patients with shorter disease duration and less damage, at
      increased dose, and that there may be better response with less progression of
      damage.

PMID- 18085736
TI  - Evaluation of paraoxonase activity in patients with mixed connective tissue
      disease.
AB  - OBJECTIVE: Mixed connective tissue disease (MCTD) is a systemic inflammatory
      autoimmune disease. The connection between inflammatory measures and
      atherosclerosis in MCTD has not been described. Paraoxonase (PON) is known to
      have an antioxidant function. We evaluated lipid profiles and PON activity in
      patients with MCTD. METHODS: Thirty-seven patients with MCTD were enrolled.
      Patients had taken no antihyperlipidemic drugs in the past 2 months. Thirty
      healthy individuals served as controls. The mean age of patients was 51.2 +/- 9.5
      years; disease duration was 11.0 +/- 7.2 years. PON activity was determined with
      spectrophotometry, von Willebrand factor (vWF) antigen was investigated with the
      immunoturbidimetry method, and thrombomodulin and antiendothelial cell antibody
      (AECA) measurements were carried out by ELISA. RESULTS: PON activity in patients
      with MCTD was significantly lower than in the controls (patients 118.5 +/- 64.6
      U/l, controls 188.0 +/- 77.6; p < 0.001). Arylesterase activity was significantly
      reduced in patients (p < 0.001). Reduction of PON activity showed a close
      correlation with the age of the patients, duration of the disease, and vascular
      events (eye, cardiac, cerebral). There was a close association between the low
      PON activity and endothelial cell activation markers (thrombomodulin, vWF, AECA).
      CONCLUSION: Our results indicate that in patients with MCTD there is an increased
      risk for atherosclerosis. In the development of atherosclerosis, besides the
      elevated levels of cholesterol and triglyceride, reduced PON concentrations and
      PON activity may play a crucial role.

PMID- 18085737
TI  - Does incorporation of aids and devices make a difference in the score of the
      health assessment questionnaire-disability index? Analysis from a scleroderma
      clinical trial.
AB  - OBJECTIVE: The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a
      commonly used musculoskeletal-targeted measure in systemic sclerosis (SSc). We
      assessed if HAQ-DI scores are different when calculated with and without
      aids/devices, and if apparent responsiveness changes when scored in these 2 ways.
      METHODS: We used data from a placebo-controlled clinical trial in diffuse SSc.
      Baseline HAQ-DI total score was calculated with and without aids/devices and
      compared using Student's t-test. We also classified the HAQ-DI scores into no-to
      mild disability (0.00-1.00), moderate disability (1.01-2.00), and severe
      disability (2.01-3.00). Responsiveness to change was evaluated using the effect
      size (ES). RESULTS: The mean (SD) baseline HAQ-DI score was 1.33 (0.68) with
      aids/devices compared to HAQ-DI score 1.16 (0.70) without aids/devices (p =
      0.03). When the baseline HAQ-DI score was categorized into no-to-mild, moderate,
      and severe disability, the proportion of patients in the no-to-mild disability
      (29% with aids/devices vs 44% without aids/devices) and moderate disability (59%
      with aids/devices vs 45% without aids/devices) groups were statistically
      different (p <0.001). The ES was similar between the 2 groups (ES = 0.01 and 0.02
      with and without aids/devices). CONCLUSION: This analysis suggests a shift from
      no-to-mild disability to moderate disability when aids/devices are incorporated
      in total HAQ-DI score. Future clinical trials in SSc should explicitly state
      whether HAQ-DI score was calculated using aids/devices.

PMID- 18085738
TI  - Increased serum interleukin 23 in patients with systemic sclerosis.
AB  - OBJECTIVE: The relationship between systemic sclerosis (SSc) and interleukin 23
      (IL-23), a cytokine associated with the differentiation of T lymphocytes, is
      unknown. We investigated serum IL-23 levels and their clinical association in
      patients with SSc. METHODS: Serum IL-23 levels were examined by ELISA in 63
      patients with SSc, 15 patients with systemic lupus erythematosus (SLE), and 31
      healthy individuals. SSc patients comprised 25 with limited cutaneous SSc and 38
      with diffuse cutaneous SSc. RESULTS: Serum IL-23 levels were significantly
      elevated in SSc patients compared to patients with SLE (p < 0.05) and controls (p
      < 0.005). Elevated serum IL-23 levels were associated with the disease duration
      (p < 0.05) and the prevalence of pulmonary fibrosis (p < 0.05), although they
      were not associated with other clinical features, including the extent of skin
      sclerosis or the severity of pulmonary fibrosis. CONCLUSION: The results suggest
      that IL-23 is associated with induction of SSc and that blockade of IL-23 can be
      a potential therapeutic strategy in early SSc.

PMID- 18085739
TI  - Transthoracic versus transesophageal echocardiography for detection of Libman
      Sacks endocarditis: a randomized controlled study.
AB  - OBJECTIVE: Libman-Sacks endocarditis in patients with systemic lupus
      erythematosus (SLE) is complicated with thromboembolism, severe valve
      regurgitation, need for high-risk valve surgery, or death. Transesophageal
      echocardiography (TEE) is highly accurate for detection of valvular heart
      disease, but there are no prospective randomized controlled series comparing
      transthoracic echocardiography (TTE) to TEE for detection of Libman-Sacks
      endocarditis. METHODS: Eighty-one patients with SLE (73 women, 8 men) with a mean
      age of 39 +/- 11 years and 75 healthy volunteers (40 women, 35 men) with a mean
      age of 35 +/- 9 years underwent paired TTE and TEE to detect valve vegetations,
      thickening, or >or= moderate mitral, tricuspid, or pulmonic >or= mild aortic
      regurgitation. Paired TTE and TEE studies of patients and controls were
      randomized and interpreted by an experienced observer unaware of subjects' data.
      RESULTS: Libman-Sacks endocarditis: (1) was more common in patients than in
      controls by both TTE and TEE (p < 0.001); and (2) was more commonly detected by
      TEE than by TTE (p </= 0.05); (3) TTE and TEE demonstrated poor agreement rates
      (kappa 0.02-0.54); and (4) considering TEE as the standard, TTE demonstrated a
      low sensitivity (63% overall, 11% for valve vegetations), low specificity (58%),
      low negative predictive value (40%), and a moderate positive predictive value
      (78%) for detection of Libman-Sacks endocarditis. CONCLUSION: TEE is superior to
      TTE for detection of Libman-Sacks endocarditis and should be considered either as
      complement to a nondiagnostic TTE or as the initial test in patients with SLE
      with suspected cardioembolism, acute or subacute Libman-Sacks endocarditis with
      moderate or worse valve dysfunction, or superimposed infective endocarditis.

PMID- 18085740
TI  - Diagnostic accuracy study of urine dipstick in relation to 24-hour measurement as
      a screening tool for proteinuria in lupus nephritis.
AB  - OBJECTIVE: Early detection of renal involvement in lupus prevents poor outcomes.
      Although published guidelines recommend urine dipstick as an appropriate
      screening test and evidence suggests a majority of American rheumatologists use
      dipstick to screen for proteinuria, the performance of this diagnostic approach
      in lupus has not been reported. We examined the validity of qualitative urine
      dipstick versus quantitative 24-hour measurement to accurately detect
      proteinuria, including low-level proteinuria. METHODS: We performed a diagnostic
      accuracy study using paired samples from the Johns Hopkins University School of
      Medicine and the Ohio State University School of Medicine lupus cohorts. All
      qualitative urine dipstick values were obtained within 1 day of a 24-hour urine
      collection. RESULTS: We analyzed the performance of 3 urine dipstick assays to
      detect proteinuria compared to 24-hour protein/creatinine ratios, using 2224
      dipstick measures from 296 patients. The sensitivity of a > or = 1+ dipstick
      result to detect quantitative proteinuria (> or = 0.50 g protein/g creatinine)
      was 82.7% for the Clinitek, 97.7% for the Atlas, and 85.5% for the Bayer assay.
      The corresponding sensitivity to detect low-level proteinuria, (0.50-0.99 g
      protein/g creatinine) was 63.1%, 96.4%, and 80.7%, respectively. The specificity
      to correctly exclude proteinuria (< 0.50 g protein/g creatinine) with
      negative/trace results was 86.1%, 62.2%, and 59.4%. There was considerable
      variability in the range of protein/creatinine ratios detected at each dipstick
      level of proteinuria. CONCLUSION: Urine dipsticks demonstrate substantial
      variability and often poor validity to accurately detect proteinuria at
      quantitative levels; this warrants further diagnostic evaluation. Clinicians
      should consider quantified proteinuria assays as a more accurate screening tool
      in the diagnostic evaluation of lupus nephritis.

PMID- 18085741
TI  - Associations of erosive arthritis with anti-cyclic citrullinated peptide
      antibodies and MHC Class II alleles in systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the associations of erosive arthritis (EA) with anti
      cyclic citrullinated peptide (anti-CCP) antibodies and major histocompatibility
      class (MHC) II alleles in systemic lupus erythematosus (SLE). METHODS: One
      hundred four patients with SLE were evaluated for arthritis and classified as EA,
      nonerosive arthritis, or no arthritis. EA was further classified as major or
      minor erosions. Sera from patients and 130 serum controls were tested for anti
      CCP2 and rheumatoid factor (RF). Patients and 117 genetic controls were genotyped
      for HLA-DRB1 and HLA-DQB1. Statistical associations were tested using chi-square
      tests and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Eight
      patients (8%) were anti-CCP+ and they accounted for 11% (8/71) of patients with
      synovitis. Twelve patients (11%) had EA. Among patients with synovitis, EA was
      associated with anti-CCP (OR 28.5, 95% CI 4.7-173.8, p = 0.001), with a weaker
      association for RF (p = 0.3). Six patients with EA had major erosions and also
      met criteria for rheumatoid arthritis (RA). Four of these patients (67%) were
      anti-CCP+. HLA-DQB1*0302 was associated with EA (p = 0.01), with similar trends
      for HLA-DRB1*0401 and 2 copies of the shared epitope (SE). There were trends for
      associations of HLA-DQB1*0302 and 2 SE copies with anti-CCP production.
      CONCLUSION: The frequency of EA in SLE is likely to be higher than previously
      reported. Anti-CCP+ patients with SLE are more likely to have EA. Anti-CCP may be
      a useful serological marker for EA for patients presenting with synovitis. Anti
      citrulline antibodies may have a pathogenic role in the development of major
      erosions, resulting in clinical features that overlap SLE with RA (rhupus).

PMID- 18085742
TI  - Influence of patient education on exercise compliance in rheumatoid arthritis: a
      prospective 12-month randomized controlled trial.
AB  - OBJECTIVE: To determine the effect of education on the exercise habits of
      patients with rheumatoid arthritis (RA) after 6 and 12 months. METHODS: We
      studied 208 outpatients recruited between June 2001 and December 2002. This was a
      prospective controlled randomized trial. The active group received a
      multidisciplinary education program, including training in home-based exercises
      and guidelines for leisure physical activity (PA). The control group received a
      booklet added to usual medical care. Compliance with home-based exercises was
      defined as a practice rate >or= 30% of the prescribed training. Compliance with
      leisure PA was defined as >or= 20% increase in Baecke questionnaire score.
      Additional assessments involved possible predictors of compliance and changes
      with regard to the compliance. RESULTS: At 6-month followup, home-based exercise
      and leisure PA compliance were significantly higher [13.5% vs 1%, respectively (p
      = 0.001); and 28.2% vs 13.8% (p = 0.02)], but were not at 12 months. Predictors
      of leisure PA compliance at 6 months included participating in the active group
      (odds ratio 2.74, 95% CI 1.17 to 6.38) and previous low leisure PA (OR 6.01, 95%
      CI 2.47 to 14.61), with decreased fatigue (FACIT-F mean -2.94 +/- 8.04 vs -0.1 +/
      7.25 for noncompliant subjects; p = 0.04) and improved psychological status
      (Arthritis Impact Measurement Scale mean -1.25 +/- 3.12 vs 0.11 +/- 3.39; p =
      0.03). CONCLUSION: Education of patients with RA may increase compliance
      especially with leisure PA, particularly when it is poor at baseline, but these
      effects are limited and short-term.

PMID- 18085743
TI  - Adalimumab plus methotrexate improved SF-36 scores and reduced the effect of
      rheumatoid arthritis (RA) on work activity for patients with early RA.
AB  - OBJECTIVE: To compare the effect of adalimumab plus methotrexate (MTX) versus MTX
      monotherapy on health-related quality of life (HRQOL) and work activities in
      patients with early rheumatoid arthritis (RA). METHODS: Patients in this PREMIER
      study subanalysis (n = 525) were randomized to adalimumab 40 mg every other week
      plus MTX or MTX monotherapy. Medical Outcome Study Short-Form 36 Health Survey
      (SF-36) scores of RA patients were compared with US population norms at Weeks 12,
      52, and 104. RESULTS: Physical Component Summary (PCS) scores at Week 12 for both
      groups improved from baseline and were significantly lower than US population
      scores (43.5 combination, 39.4 MTX, 49.4 US norm; p< 0.001). At Week 52, PCS
      score for adalimumab plus MTX was similar to that of the US population (47.5 vs
      48.3; p = 0.25), while the PCS score for MTX was not similar to that of the US
      population (44.2 vs 48.3; p < 0.001). Criterion- and content-based
      interpretations for between-treatment differences in PCS scores suggest that
      those receiving combination therapy had fewer employment difficulties than those
      receiving MTX. CONCLUSION: After 2 years, HRQOL for patients with early RA
      treated with adalimumab plus MTX improved to US norms. Combination therapy had
      reduced the influence of RA on work activity.

PMID- 18085744
TI  - Synthesis and in vivo evaluation of halogenated N,N-dimethyl-2-(2'-amino-4'
      hydroxymethylphenylthio)benzylamine derivatives as PET serotonin transporter
      ligands.
AB  - N, N-dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine (38),
      substituted on ring A, was reported to display high binding affinity and
      selectivity to the human brain serotonin transporter (SERT). In an attempt to
      explore the potential of compounds substituted on ring B of the phenylthiophenyl
      core structure, three derivatives of 38 were synthesized: N, N-dimethyl-2-(2'
      amino-4'-hydroxymethyl-phenylthio)-5-fluorobenzylamine (35), N, N-dimethyl-2-(2'
      amino-4'-hydroxymethyl-phenylthio)-5-bromobenzylamine (36), and N, N-dimethyl-2
      (2'-amino-4'-hydroxymethyl-phenylthio)-5-iodobenzylamine (37). The in vitro
      binding studies in cells transfected with human SERT, norepinephrine transporter
      (NET), and dopamine transporter (DAT) showed that 35, 36, and 37 exhibited high
      SERT affinity with K is (SERT) = 1.26, 0.29, and 0.31 nM (vs [(3)H]citalopram),
      respectively. [(11)C]-(35), [(11)C]-(36), and [(11)C]-( 37) were prepared by
      methylation of their monomethyl precursors 16, 17, and 18, with
      [(11)C]iodomethane in 28, 11, and 14% radiochemical yields, respectively. The
      microPET images of [(11)C]-(35), [(11)C]-(36), and [(11)C]-(37) showed high
      uptake in the monkey brain regions rich in SERT with peak midbrain to cerebellum
      ratios of 3.41, 3.24, and 3.00 at 85 min post-injection, respectively. In vivo
      bindings of [(11)C]-(35), [(11)C]-(36), and [(11)C]-(37) were shown to be
      specific to the SERT as displacement with citalopram (a potent SERT ligand)
      reduced radioactivity in SERT-rich regions to the cerebellum level. These results
      suggest that [(11)C]-(35), [(11)C]-(36), and [(11)C]-(37) could be potential
      agents for mapping human SERT by PET and radiolabeling 37 with iodine-123, which
      could afford the first SPECT SERT imaging agent exhibiting fast kinetics.

PMID- 18085747
TI  - Pioneering perspectives on asymmetric hydrogenation.

PMID- 18085745
TI  - Aerocellulose: new highly porous cellulose prepared from cellulose-NaOH aqueous
      solutions.
AB  - New highly porous pure cellulose aerogel-like material called "aerocellulose" was
      prepared from aqueous cellulose/NaOH solutions. Solutions were gelled to obtain
      shaped three-dimensional objects, then cellulose was regenerated and dried in
      supercritical conditions using CO2. The porosity of aerocellulose is higher than
      95% with pore sizes distribution from a few tens of nanometers to a few tens of
      micrometers. The internal specific surface area is around 200-300 m2/g, and
      density ranges from 0.06 to 0.3 g/cm3, depending on the preparation conditions.
      The influence of cellulose DP and concentration, of the addition of a surfactant
      leading to solution foaming, of gelation conditions and the temperature and
      acidity of regenerating bath on the morphology of aerocellulose has been studied.
      The results are compared with another type of aerocellulose that was prepared
      from cellulose/NMMO solutions.

PMID- 18085748
TI  - Enantioselective organocatalytic transfer hydrogenation reactions using Hantzsch
      esters.
AB  - Within the realm of catalytic asymmetric hydrogenation, the focus continues to be
      on the use of chiral metal complexes in conjunction with a hydrogen source.
      Recently, the widespread development of organocatalysis, including the invention
      of iminium activation, has led to the discovery of many new enantioselective
      transformations. Based on this strategy, a number of bioinspired processes for
      the enantioselective organocatalytic transfer hydrogenation of alpha,beta
      unsaturated carbonyl compounds and imines have been discovered. These topics will
      be the focus of this Account.

PMID- 18085749
TI  - Tandem mass spectrometry characteristics of silver-cationized polystyrenes:
      backbone degradation via free radical chemistry.
AB  - The [M + Ag](+) ions of polystyrene (PS) oligomers are formed by matrix-assisted
      laser desorption/ionization, and their fragmentation characteristics are
      determined by tandem mass spectrometry experiments in a quadrupole/time-of-flight
      mass spectrometer. Collisionally activated dissociation (CAD) of [M + Ag](+)
      starts with random homolytic C-C bond cleavages in the PS chain, which generate
      radical ions carrying either the initiating (a(n*), b(n*)) or the terminating
      (y(n*), z(n*)) chain end and primary (a(n*), y(n*)) or benzylic (b(n*), z(n*))
      radical centers. The fragments ultimately observed arise by consecutive, radical
      induced dissociations. The primary radical ions mainly decompose by monomer
      evaporation and, to a lesser extent, by beta-H(*) loss. The benzylic radical ions
      primarily decompose by 1,5-H rearrangement (backbiting) followed by beta C-C bond
      scissions; this pathway leads to either closed-shell fragments with CH(2) end
      groups, internal fragments with 2-3 repeat units, or truncated benzylic
      b(n*)/z(n*) radical ions that can undergo anew backbiting. The same internal
      fragments are produced in all backbiting steps; hence, these fragments and small
      benzylic radical ions (which cannot undergo backbiting) dominate the low-mass
      region of the CAD spectra, while the less abundant closed-shell fragments with
      CH(2) end groups (a(n)/y(n)) dominate the medium- and high-mass regions. The
      latter fragments are suitable for determining the individual initiating and
      terminating end groups, whereas the internal ions could be valuable in sequence
      analyses of styrene copolymers.

PMID- 18085751
TI  - Tandem mass spectrometry characteristics of silver-cationized polystyrenes:
      internal energy, size, and chain end versus backbone substituent effects.
AB  - The Ag(+) adducts of polystyrene (PS) oligomers with different sizes (6-19 repeat
      units) and initiating (alpha) or terminating (omega) end groups mainly decompose
      via free radical chemistry pathways upon collisionally activated dissociation.
      This reactivity is observed for ions formed by matrix-assisted laser
      desorption/ionization as well as electrospray ionization. With end groups lacking
      weak bonds (robust end groups), dissociation starts with random homolytic C-C
      bond cleavages along the PS chain, which lead to primary and benzylic radical
      ions containing either of the chain ends. The primary radical ions mainly
      depolymerize by successive beta C-C bond scissions. For the benzylic radical
      ions, two major pathways are in competition, namely, depolymerization by
      successive beta C-C bond scissions and backbiting via 1,5-H rearrangement
      followed by beta C-C bond scissions. The extent of backbiting decreases with
      internal energy. With short PS chains, the primary radical ions also undergo
      backbiting involving 1,4- and 1,6-H rearrangements; however, this process becomes
      negligible with longer chains. If the polystyrene contains a labile substituent
      at a chain end, this substituent is eliminated easily and, thus, not contained in
      the majority of observed fragments. Changes in the PS backbone structure can have
      a dramatic effect on the resulting dissociation chemistry. This is demonstrated
      for poly(alpha-methylstyrene), in which backbiting is obstructed due to the lack
      of benzylic H atoms; instead, this backbone connectivity promotes 1,2-phenyl
      shifts in the primary radical ions formed after initial C-C bond homolyses as
      well as H atom transfers between the incipient primary and benzylic radicals
      emerging from these homolyses.

PMID- 18085750
TI  - Determination of global protein turnover in stressed mycobacterium cells using
      hybrid-linear ion trap-fourier transform mass spectrometry.
AB  - We determined the global protein turnover profiles for Mycobacterium smegmatis
      under acid shock and iron starvation conditions using a simple (15)N isotope
      doping technique and a complete medium replacement method for chasing. We used a
      high-resolution hybrid-linear ion trap-Fourier transform mass spectrometer
      coupled with nanoliquid chromatography separation to measure protein turnover
      values for 151 proteins over a dynamic range of 3 orders of magnitude ranging
      from about 0.2 to 500. Of these 151 proteins, 31 had significant protein turnover
      changes (p <0.05) at both stress conditions and had protein turnover values
      increased or decreased by more than 2-fold under at least one stress condition.
      Protein turnover increased under acid shock for 28 of the 31 proteins but
      decreased under iron starvation for all the 31 proteins. Only two proteins had
      protein turnover lowered by more than 2-fold (p <0.05) under both stress
      conditions, including an ATP synthase F1 beta subunit (MSMEG4921; AtpD) and a
      catalase/peroxidase (MSMEG6346; KatG). KatG is required for in vivo activation of
      isoniazid to be bacterialcidal. Decrease of KatG protein turnover under both
      stress conditions supports the view that isoniazid may induce a dormancy program
      in mycobacteria, which in turn limits the efficacy of this drug against dormant
      subpopulation of mycobacteria. Thus, measuring protein turnover in stressed
      Mycobacterium cells has implications in understanding drug action and resistance
      mechanisms.

PMID- 18085752
TI  - Multiple ionization mass spectrometry strategy used to reveal the complexity of
      metabolomics.
AB  - A multiple ionization mass spectrometry strategy is presented based on the
      analysis of human serum extracts. Chromatographic separation was interfaced
      inline with the atmospheric pressure ionization techniques electrospray
      ionization (ESI) and atmospheric pressure chemical ionization (APCI) in both
      positive (+) and negative (-) ionization modes. Furthermore, surface-based matrix
      assisted laser desorption/ionization (MALDI) and desorption ionization on silicon
      (DIOS) mass spectrometry were also integrated with the separation through
      fraction collection and offline mass spectrometry. Processing of raw data using
      the XCMS software resulted in time-aligned ion features, which are defined as a
      unique m/z at a unique retention time. The ion feature lists obtained through LC
      MS with ESI and APCI interfaces in both +/- ionization modes were compared, and
      unique ion tables were generated. Nonredundant, unique ion features, were defined
      as mass numbers for which no mass numbers corresponding to [M + H](+), [M - H](
      ), or [M + Na](+) were observed in the other ionization methods at the same
      retention time. Analysis of the extracted serum using ESI for both (+) and (-)
      ions resulted in >90% additional unique ions being detected in the (-) ESI mode.
      Complementing the ESI analysis with APCI resulted in an additional approximately
      20% increase in unique ions. Finally, ESI/APCI ionization was combined with
      fraction collection and offline-MALDI and DIOS mass spectrometry. The parts of
      the total ion current chromatograms in the LC-MS acquired data corresponding to
      collected fractions were summed, and m/z lists were compiled and compared to the
      m/z lists obtained from the DIOS/MALDI spectra. It was observed that, for each
      fraction, DIOS accounted for approximately 50% of the unique ions detected. These
      results suggest that true global metabolomics will require multiple ionization
      technologies to address the inherent metabolite diversity and therefore the
      complexity in and of metabolomics studies.

PMID- 18085753
TI  - Theoretical study of hydrated copper(II) interactions with guanine: a
      computational density functional theory study.
AB  - Optimization of the hydrated Cu(II)(N7-guanine) structures revealed a number of
      minima on the potential energy surface. For selected structures, energy
      decompositions together with the determination of electronic properties (partial
      charges and electron spin densities) were performed. In the complexes of guanine
      with the bare copper cation and that with the monoaqua ligated cation, an
      electron transfer from guanine to Cu(II) was observed, resulting in a Cu(I)
      guanine(+) type of complex. Conformers with two aqua ligands are borderline
      systems characterized by a Cu partial charge of +0.7e and a similar value of the
      spin density (0.6e) localized on guanine. When tetracoordination of copper was
      achieved, only then the prevailing electron spin density is unambiguously
      localized on copper. The energetic preference of diaqua-Cu-(N7,O6-guanine) over
      triaqua-Cu-(N7-guanine) was found for the four-coordinate structures. However,
      the energy difference between these two conformations decreases with the number
      of water molecules present in the systems, and in complexes with five water
      molecules this preference is preserved only at DeltaG level where thermal and
      entropy terms are included.

PMID- 18085754
TI  - Approach to the atmospheric chemistry of methyl nitrate and methylperoxy nitrite.
      Chemical mechanisms of their formation and decomposition reactions in the gas
      phase.
AB  - Potential energy surfaces, minimum energy reaction paths, minima, transition
      states, reaction barriers, and conical intersections for the most important
      atmospheric reactions of methyl nitrate (CH(3)ONO(2)) and methylperoxy nitrite
      (C(3)HOONO) on the electronic ground state have been studied (i) with the second
      order multiconfigurational perturbation theory (CASPT2) by computation of
      numerical energy gradients for stationary points and (ii) with the density
      functional theory (DFT). The proposed mechanism explains the conversion of
      unreactive alkyl peroxy radicals into alkoxy radicals: CH(3)O(2) + NO <=>
      CH(3)OONO <=> CH(3)O + NO(2) left arrow over right arrow CH(3)ONO(2).
      Additionally, several discrepancies found in the comparison of the results
      obtained from the two employed approaches are analyzed. CASPT2 predicts that all
      dissociation reactions into radicals occur without an extra exit energy barrier.
      In contrast, DFT finds transition states for the dissociations of cis- and trans
      methylperoxy nitrite into CH(3)O + NO(2). Furthermore, multiconfigurational
      methods [CASPT2 and complete active space SCF (CAS-SCF)] predict the
      isomerization of CH3ONO2 to CH3OONO to occur in a two-step mechanism: (i)
      CH(3)ONO(2) --> CH(3)O + NO(2); and (ii) CH(3)O + NO(2) --> CH(3)OONO. The reason
      for this has to do with the coupling of the ground electronic state with the
      first excited state. Therefore, it is demonstrated that DFT methods based on
      single determinantal wave functions give an incorrect picture of the
      aforementioned reaction mechanisms.

PMID- 18085755
TI  - Graphene layer growth chemistry: five- and six-member ring flip reaction.
AB  - Reaction pathways are presented for hydrogen-mediated isomerization of a five-
      and six-member carbon ring complex on the zigzag edge of a graphene layer. A new
      reaction sequence that reverses the orientation of the ring complex, or "flips"
      it, was identified. Competition between the flip reaction and the "ring
      separation" was examined. Ring separation is the reverse of the five- and six
      member ring complex formation reaction, previously reported as "ring collision".
      The elementary steps of the pathways were analyzed using density functional
      theory (DFT). Rate coefficients were obtained by solution of the energy master
      equation and classical transition-state-theory utilizing the DFT energies,
      frequencies, and geometries. The results indicate that the flip reaction pathway
      dominates the separation reaction and should be competitive with other pathways
      important to the graphene zigzag edge growth in high-temperature environments.

PMID- 18085756
TI  - Detection and evaluation of hydrogen bond strength in nucleic acid base pairs.
AB  - The strengths of N-H---N and N-H---O hydrogen bonds in 15 nucleic acid base pairs
      have been investigated using different descriptors. Geometrical and energetic
      criteria, atoms in molecules topological parameters, natural bond orbital
      analysis, and spectroscopic measurements have been used to detect the H-bonds and
      evaluate their strengths in the intermolecular interactions between five nucleic
      acid bases. Different correlations have been obtained between many of these
      descriptors to provide a global view of H-bond interaction. We found good linear
      correlations for the dependence of some descriptors such as atomic
      interpenetration and hyperconjugation energy on density at bond critical point,
      while others like destabilization of H-atom energy, variation in N-H frequency,
      and NMR parameters correlate in a much worse fashion. The calculations suggest
      that almost all H-bonds in different base pairs belong to medium strength H
      bonds. We found in thymine the H-bond interaction is more likely through the
      amide-type oxygen while the situation is reverse for uracil in which the urea
      type oxygen is more accessible to form an H-bond. Cytosine and guanine can also
      form H-bonds via their amine-type or amide-type nitrogens. In cytosine, the amine
      type nitrogen is involved in an N-H---O bond interaction, while, in guanine, the
      amide-type nitrogen has a greater contribution to H-bond interaction.

PMID- 18085757
TI  - Intramolecular hydrogen bonding and cooperative interactions in carbohydrates via
      the molecular tailoring approach.
AB  - In spite of many theoretical and experimental attempts for understanding
      intramolecular hydrogen bonding (H-bonding) in carbohydrates, a direct
      quantification of individual intramolecular H-bond energies and the cooperativity
      among the H-bonded networks has not been reported in the literature. The present
      work attempts, for the first time, a direct estimation of individual
      intramolecular O-H...O interaction energies in sugar molecules using the recently
      developed molecular tailoring approach (MTA). The estimated H-bond energies are
      in the range of 1.2-4.1 kcal mol(-1). It is seen that the OH...O equatorial
      equatorial interaction energies lie between 1.8 and 2.5 kcal mol(-1), with axial
      equatorial ones being stronger (2.0-3.5 kcal mol(-1)). The strongest bonds are
      nonvicinal axial-axial H-bonds (3.0-4.1 kcal mol(-1)). This trend in H-bond
      energies is in agreement with the earlier reports based on the water-water H-bond
      angle, solvent-accessible surface area (SASA), and (1)H NMR analysis. The
      contribution to the H-bond energy from the cooperativity is also estimated using
      MTA. This contribution is seen to be typically between 0.1 and 0.6 kcal mol(-1)
      when H-bonds are a part of a relatively weak equatorial-equatorial H-bond network
      and is much higher (0.5-1.1 kcal mol(-1)) when H-bonds participate in an axial
      axial H-bond network.

PMID- 18085758
TI  - Electronic ground state of higher acenes.
AB  - We examine the electronic ground states of acenes with different numbers of fused
      benzene rings (up to 40) by using first principles density functional theory.
      Their properties are compared with those of infinite polyacene. We find that the
      ground state of acenes that consist of more than seven fused benzene rings is an
      antiferromagnetic (in other words, open-shell singlet) state, and we show that
      this singlet is not necessarily a diradical, because the spatially separated
      magnetizations for the spin-up and spin-down electrons increase with the size of
      the acene. For example, our results indicate that there are about four spin-up
      electrons localized at one zigzag edge of 20-acene. The reason that both acenes
      and polyacene have the antiferromagnetic ground state is due to the zigzag-shaped
      boundaries, which cause pi-electrons to localize and form spin orders at the
      edges. Both wider graphene ribbons and large rectangular-shaped polycyclic
      aromatic hydrocarbons have been shown to share this antiferromagnetic ground
      state. Therefore, we demonstrate that the pi-electronic structures of higher
      acenes and polyacene are still dictated by the zigzag edges, and our results
      provide a consistent description of their electronic ground state.

PMID- 18085759
TI  - Structural, electronic, and magnetic properties of Con(benzene)m complexes.
AB  - The structural, electronic, and magnetic properties of cobalt-benzene complexes
      (Co(n)Bz(m), n, m = 1-4, m = n, n + 1) have been explored within the framework of
      an all electron gradient-corrected density functional theory. Sandwich
      conformations are energetically preferred for the smallest series of n, m = 1-2,
      rice-ball structures are for larger sizes with n > or = 3, and both motifs
      coexist for Co(2)Bz(3). The rice-ball clusters of (3, 3) and (4, 4) are more
      stable than (3, 4) having a relative large binding energy and HOMO-LUMO gap
      whereas smaller sandwich clusters have highly kinetic stability at (n, n + 1).
      The computed ionization potentials and magnetic moments of Co(n)Bz(m) are in good
      agreement with the measured values overall; the present results suggest that the
      measured moments are averages reflecting mixtures of a few nearly isoenergetic
      isomers having different spin states. The magnetism of the complexes mainly comes
      from Co atoms with a Bz molecule only possessing very small moments.
      Ferromagnetic ordering is energetically preferred for smaller complexes with n =
      1-3 whereas antiferromagnetic ordering is favored for (4, 4). The relatively
      smaller moments of Con clusters in a Bz matrix indicate that Bz molecules play an
      attenuation role to the magnetism of the complexes.

PMID- 18085760
TI  - An ab initio and density functional theory study of the structure and bonding of
      sulfur ylides.
AB  - Sulfur ylides are useful synthetic intermediates that are formed from the
      interaction between singlet carbenes and sulfur-containing molecules. Partial
      double-bond character frequently has been proposed as a key contributor to the
      stability of sulfur ylides. Calculations at the B3LYP, MP2, and CCSD(T) levels of
      theory employing various basis sets have been performed on the sulfur ylides
      H(2)S-CH(2) and (CH(3))(2)S-CH(2) in order to investigate the structure and
      bonding of these systems. The following general properties of sulfur ylides were
      observed from the computational studies: C-S bond distances that are close in
      length to that of a typical C-S double bond, high charge transfer from the
      sulfide to the carbene, and large torsional rotation barriers. Analysis of the
      sulfur ylide charge distribution indicates that the unusually short C-S bond
      distance can be attributed in part to the electrostatic attraction between highly
      oppositely charged carbon and sulfur atoms. Furthermore, n --> sigma*
      stabilization arising from donation of electron density from the carbon lone pair
      orbital into S-H or S-C antibonding orbitals leads to larger than expected
      torsional barriers. Finally, natural resonance theory analysis indicates that the
      bond order of the sulfur ylides H(2)S-CH(2) and (CH(3))(2)S-CH(2) is 1.4-1.5,
      intermediate between a single and double bond.

PMID- 18085761
TI  - Thioperoxy derivative generated by UV-induced transformation of N-hydroxypyridine
      2(1H)-thione isolated in low-temperature matrixes.
AB  - Photochemical transformations of N-hydroxypyridine-2(1H)-thione and its
      deuterated isotopologue were studied using the matrix-isolation technique. Low
      temperature Ar and N2 matrixes containing monomers of this compound were
      irradiated with continuous-wave near-UV light. Photogeneration of two products
      was observed in these experiments. The relative population of these
      photogenerated species was found to be dependent on the wavelength of the UV
      light used for irradiation. By comparison of the IR spectra of the photoproducts
      with the spectra simulated theoretically at the DFT(B3LYP)/6-311++G(d, p) level,
      the final and the intermediate products were identified as rotameric forms of 2
      hydroxysulfanyl-pyridine. This is the first report on generation of this
      thioperoxy derivative of pyridine. The mechanism of photogeneration of 2
      hydroxysulfanyl-pyridine involves a photoinduced cleavage of the N-O bond in N
      hydroxypyridine-2(1H)-thione, generation of the .OH radical weakly bound with the
      remaining pyridylthiyl radical, and recombination of these two radicals by
      formation of the new -S-O- bond. A theoretical model supporting this
      interpretation was constructed on the basis of approximate coupled cluster (CC2)
      calculations of the potential energy surfaces of the ground and first excited
      singlet electronic states of the system. After electronic excitation of the
      monomeric N-hydroxypyridine-2(1H)-thione, the molecule evolves to the conical
      intersection with the potential energy surface of the ground state and then to
      the global minimum corresponding to 2-hydroxysulfanyl-pyridine.

PMID- 18085762
TI  - Photophysics and photochemistry of imipramine, desimipramine, and clomipramine in
      several solvents: a fluorescence, 266 nm laser flash, and theoretical study.
AB  - Imipramine (IPA) and its derivatives are used widely for the treatment of
      depression and other mental disorders. Although there are more than 20 FDA
      approved antidepressant drugs, the search continues for better compounds with
      fewer deleterious side effects and higher efficacy. Over the past decade, several
      classes of antipsychotic drugs have been developed, which-in spite of their
      structural diversity-share an ability to modulate neurotransmission and to
      produce undesirable side effects. Phototoxicity is one of the most important side
      effects noted in treatment with tricyclic antidepressants (TCAs), but its
      mechanism has not yet been elucidated. To develop new knowledge regarding the
      relationship between the structure and the photophysics of these TCAs, we
      measured the photophysical properties of IPA, desimipramine (DIPA), and
      clomipramine (CIPA) in different solvents. The electronic configurations for the
      ground and the first excited singlet states were calculated using the AM1/RHF/CI
      and the AM1/RHF/HE semiempirical quantum theoretical methods, respectively. The
      ground-state properties are solvent-independent, while the emission maxima are
      red-shifted with increasing solvent polarity/polarizability. However, the
      fluorescence quantum yield is relatively low in all of the tested solvents
      (phif<0.02). The primary transient intermediates produced by 266 nm high
      intensity laser photolysis are the solvated electron and the corresponding
      radical cation, with a negligible contribution of triplet-triplet absorption. The
      properties determined for the primary transients generated with a 266 nm laser
      flash are consistent with the photodamaging effects generated through a limited
      radical mechanism.

PMID- 18085763
TI  - DNA-surfactant interactions: a procedure for determination group contributions.
AB  - A procedure, based on the measurement of pyren-1-carboxyaldehyde fluorescence,
      has been used to obtain the free energy corresponding to the interaction of
      several surfactants of alkyltrimethylammonium-type RN(CH3)3+ and DNA. These free
      energies depend linearly on the number of carbon atoms in the tail of the
      surfactant. In this way, it was possible to determine the -CH2-/DNA interaction
      free energy as well as the free energy of interaction of DNA and the head group
      of the surfactants. According to the values of these free energies, the
      surfactant/DNA interaction is mainly electrostatic, for the surfactants used in
      this work. However, for long enough tails the free energy corresponding to the
      hydrophobic interaction can reach the same value as the electrostatic one. The
      procedure used in this work could be extended to the measurement of other
      group/DNA interactions.

PMID- 18085764
TI  - Deformation of a sheet with coupling between elasticity and concentration.
AB  - We investigate a simple model for equilibrium deformation of a sheet with
      concentration-dependent elasticity. The model is motivated by several physical
      situations where deformation of a sheet is modulated by concentration of a mobile
      species, for example, a quasi-2D array of carbon nanotubes. Elasticity of the
      sheet is modeled using a free energy functional that includes concentration
      dependent potential energies, and a free energy of mixing. We show that the sheet
      responds to imposed distortion by rearranging its constituents and can do so in a
      smooth and stable manner only for sufficiently small distortion. For larger
      distortions, through phase plane and numerical analysis, we consider how the
      system can meet boundary conditions through nonsmooth solutions.

PMID- 18085765
TI  - Diffusion in nanoporous phases: size dependence and levitation effect.
AB  - Self-diffusivity, D, of diffusants in widely differing mediums such as liquids
      (e.g., solution), porous solids (e.g., guests in zeolites), or ions in polar
      solvents exhibit strong size dependence. We discuss the nature of the size
      dependence observed in these systems. Altogether, different theoretical
      approaches have been proposed to understand the nature of size dependence of D
      not only across these widely differing systems but even in just one medium or
      class of systems such as, for example, ions in polar solvents. But molecular
      dynamics investigations in the past decade have shown that the size dependence of
      self-diffusion in guest-porous solids could have origins in the mutual
      cancellation of forces that occurs when the size of the diffusant is comparable
      to the size of the void. The effect leading to the maximum in D is known as the
      levitation effect (LE). Such a cancellation is a consequence of symmetry. This
      effect exists in all porous solids irrespective of the geometrical and
      topological details of the pore network provided by the solid. Recent studies
      show that the levitation effect and size-dependent diffusivity maximum exists for
      uncharged solutes in solvents. One of the consequences of this is the breakdown
      in the Stokes-Einstein relationship over a certain range of solute-solvent size
      ratio. Experimental measurements of ionic conductivity over the past hundred
      years have found the existence of a size-dependent diffusivity maximum leading to
      violation of the Walden's rule for ions in polar solvents. Molecular dynamics
      simulations and experimental data suggest that even this maximum has its origin
      in LE. Simulation studies of impurity atom diffusion in close-packed solids as
      well as ions in superionic and other solids suggest the existence of a size
      dependent diffusivity maximum in these materials as well. The levitation effect
      is a universal effect leading to a maximum in diffusivity of a diffusant in a
      variety of condensed matter phases. The only condition for its existence appears
      to be the presence of van der Waals or electrostatic interactions.

PMID- 18085766
TI  - A quantitative coarse-grain model for lipid bilayers.
AB  - A simplified particle-based computer model for hydrated phospholipid bilayers has
      been developed and applied to quantitatively predict the major physical features
      of fluid-phase biomembranes. Compared with available coarse-grain methods, three
      novel aspects are introduced. First, the main electrostatic features of the
      system are incorporated explicitly via charges and dipoles. Second, water is
      accurately (yet efficiently) described, on an individual level, by the soft
      sticky dipole model. Third, hydrocarbon tails are modeled using the anisotropic
      Gay-Berne potential. Simulations are conducted by rigid-body molecular dynamics.
      Our technique proves 2 orders of magnitude less demanding of computational
      resources than traditional atomic-level methodology. Self-assembled bilayers
      quantitatively reproduce experimental observables such as electron density,
      compressibility moduli, dipole potential, lipid diffusion, and water
      permeability. The lateral pressure profile has been calculated, along with the
      elastic curvature constants of the Helfrich expression for the membrane bending
      energy; results are consistent with experimental estimates and atomic-level
      simulation data. Several of the results presented have been obtained for the
      first time using a coarse-grain method. Our model is also directly compatible
      with atomic-level force fields, allowing mixed systems to be simulated in a
      multiscale fashion.

PMID- 18085767
TI  - Polarizable and nonpolarizable force fields for alkyl nitrates.
AB  - Quantum-chemistry-based many-body polarizable and two-body nonpolarizable atomic
      force fields were developed for alkyl nitrate liquids and pentaerythritol
      tetranitrate (PETN) crystal. Bonding, bending, and torsional parameters, partial
      charges, and atomic polarizabilities for the polarizable force field were
      determined from gas-phase quantum chemistry calculations for alkyl nitrate
      oligomers and PETN performed at the MP2/aug-cc-pvDz level of theory. Partial
      charges for the nonpolarizable force field were determined by fitting the dipole
      moments and electrostatic potential to values for PETN molecules in the crystal
      phase obtained from molecular dynamics simulations using the polarizable force
      field. Molecular dynamics simulations of alkyl nitrate liquids and two polymorphs
      of PETN crystal demonstrate the ability of the quantum-chemistry-based force
      fields to accurately predict thermophysical and mechanical properties of these
      materials.

PMID- 18085768
TI  - Two-dimensional reaction free energy surfaces of catalytic reaction: effects of
      protein conformational dynamics on enzyme catalysis.
AB  - We introduce a two-dimensional (2D) multisurface reaction free energy description
      of the catalytic cycle that explicitly connects the recently observed multi-time
      scale conformational dynamics as well as dispersed enzymatic kinetics to the
      classical Michaelis-Menten equation. A slow conformational motion on a collective
      enzyme coordinate Q facilitates the catalytic reaction along the intrinsic
      reaction coordinate X, providing a dynamic realization of Pauling's well-known
      idea of transition-state stabilization. The catalytic cycle is modeled as
      transitions between multiple displaced harmonic wells in the XQ space
      representing different states of the cycle, which is constructed according to the
      free energy driving force of the cycle. Subsequent to substrate association with
      the enzyme, the enzyme-substrate complex under strain exhibits a nonequilibrium
      relaxation toward a new conformation that lowers the activation energy of the
      reaction, as first proposed by Haldane. The chemical reaction in X is thus
      enslaved to the down hill slow motion on the Q surface. One consequence of the
      present theory is that, in spite of the existence of dispersive kinetics, the
      Michaelis-Menten expression of the catalysis rate remains valid under certain
      conditions, as observed in recent single-molecule experiments. This dynamic
      theory builds the relationship between the protein conformational dynamics and
      the enzymatic reaction kinetics and offers a unified description of enzyme
      fluctuation-assisted catalysis.

PMID- 18085769
TI  - Theory of stochastic dipolar recoupling in solid-state nuclear magnetic
      resonance.
AB  - Dipolar recoupling techniques in solid-state nuclear magnetic resonance (NMR)
      consist of radio frequency (rf) pulse sequences applied in synchrony with magic
      angle spinning (MAS) that create nonzero average magnetic dipole-dipole couplings
      under MAS. Stochastic dipolar recoupling (SDR) is a variant in which randomly
      chosen rf carrier frequency offsets are introduced to cause random phase
      modulations of individual pairwise couplings in the dipolar spin Hamiltonian.
      Several aspects of SDR are investigated through analytical theory and numerical
      simulations: (1) An analytical expression for the evolution of nuclear spin
      polarization under SDR in a two-spin system is derived and verified through
      simulations, which show a continuous evolution from coherent, oscillatory
      polarization exchange to incoherent, exponential approach to equilibrium as the
      range of random carrier offsets (controlled by a parameter f(max)) increases; (2)
      in a many-spin system, polarization transfers under SDR are shown to be described
      accurately by a rate matrix in the limit of large f(max), with pairwise transfer
      rates that are proportional to the inverse sixth power of pairwise internuclear
      distances; (3) quantum mechanical interferences among noncommuting pairwise
      dipole-dipole couplings, which are a complicating factor in solid-state NMR
      studies of molecular structures by traditional dipolar recoupling methods, are
      shown to be absent from SDR data in the limit of large f(max), provided that
      coupled nuclei have distinct NMR chemical shifts.

PMID- 18085770
TI  - The ultrafast charge-transfer-to-solvent dynamics of iodide in tetrahydrofuran.
      1. Exploring the roles of solvent and solute electronic structure in condensed
      phase charge-transfer reactions.
AB  - Although they represent the simplest possible charge-transfer reactions, the
      charge-transfer-to-solvent (CTTS) dynamics of atomic anions exhibit considerable
      complexity. For example, the CTTS dynamics of iodide in water are very different
      from those of sodide (Na-) in tetrahydrofuran (THF), leading to the question of
      the relative importance of the solvent and solute electronic structures in
      controlling charge-transfer dynamics. In this work, we address this issue by
      investigating the CTTS spectroscopy and dynamics of I- in THF, allowing us to
      make detailed comparisons to the previously studied I-/H2O and Na-/THF CTTS
      systems. Since THF is weakly polar, ion pairing with the counterion can have a
      substantial impact on the CTTS spectroscopy and dynamics of I- in this solvent.
      In this study, we have isolated "counterion-free" I- in THF by complexing the Na+
      counterion with 18-crown-6 ether. Ultrafast pump-probe experiments reveal that
      THF-solvated electrons (e-THF) appear 380 +/- 60 fs following the CTTS excitation
      of "free" I- in THF. The absorption kinetics are identical at all probe
      wavelengths, indicating that the ejected electrons appear with no significant
      dynamic solvation but rather with their equilibrium absorption spectrum. After
      their initial appearance, ejected electrons do not exhibit any additional
      dynamics on time scales up to approximately 1 ns, indicating that geminate
      recombination of e-THF with its iodine atom partner does not occur. Competitive
      electron scavenging measurements demonstrate that the CTTS excited state of I- in
      THF is quite large and has contact with scavengers that are several nanometers
      away from the iodide ion. The ejection time and lack of electron solvation
      observed for I- in THF are similar to what is observed following CTTS excitation
      of Na- in THF. However, the relatively slow ejection time, the complete lack of
      dynamic solvation, and the large ejection distance/lack of recombination dynamics
      are in marked contrast to the CTTS dynamics observed for I- in water, in which
      fast electron ejection, substantial solvation, and appreciable recombination have
      been observed. These differences in dynamical behavior can be understood in terms
      of the presence of preexisting, electropositive cavities in liquid THF that are a
      natural part of its liquid structure; these cavities provide a mechanism for
      excited electrons to relocate to places in the liquid that can be nanometers
      away, explaining the large ejection distance and lack of recombination following
      the CTTS excitation of I- in THF. We argue that the lack of dynamic solvation
      observed following CTTS excitation of both I- and Na- in THF is a direct
      consequence of the fact that little additional relaxation is required once an
      excited electron nonadiabatically relaxes into one of the preexisting cavities.
      In contrast, liquid water contains no such cavities, and CTTS excitation of I- in
      water leads to local electron ejection that involves substantial solvent
      reorganization.

PMID- 18085771
TI  - Effect of ultrasound frequency on pulsed sonolytic degradation of octylbenzene
      sulfonic acid.
AB  - It has been shown that pulsed ultrasound can influence the amount of surfactant
      that can adsorb to and decompose at the surface of cavitation bubbles. However,
      the effect of ultrasound frequency on this process has not been considered. The
      current study investigates the effect of ultrasound frequency on the pulsed
      sonolytic degradation of octyl benzenesulfonate (OBS). Furthermore, the effect of
      pulsing and ultrasound frequency on the rate of *OH radical formation was
      determined. OBS degradation rates were compared to the rates of *OH radical
      formation. In this way, conclusions were made regarding the relative importance
      of accumulation of OBS at cavitation bubble surfaces versus sonochemical activity
      to the sonochemical decomposition of OBS under different conditions of sonolysis.
      Comparisons of the data in this way indicate that sonolytic degradation of OBS
      depends on both the sonochemical activity (i.e., *OH yield) and the accumulation
      of OBS on cavitation bubble surfaces. However, under a certain set of pulsing and
      ultrasound frequency exposure conditions, enhanced accumulation of OBS at the
      gas/solution interface of cavitation bubbles is the sole mechanism of enhanced
      degradation due to pulsing. On the basis of this finding, conclusions on how
      pulsing at various ultrasound frequencies affects cavitation bubbles were made.

PMID- 18085772
TI  - Using Grote-Hynes theory to quantify dynamical effects on the reaction rate of
      enzymatic processes. The case of methyltransferases.
AB  - Dynamical effects have recently received much attention in the context of the
      theoretical investigation of enzymatic catalysis. In this paper we use a
      combination of Grote-Hynes theory with quantum mechanical/molecular mechanical
      modeling that is a powerful tool to understand and quantify these dynamical
      effects in a particular enzyme, the glycine N-methyltransferase (GNMT).
      Comparison of the results obtained for this enzyme with another methyltransferase
      (catechol O-methyltransferase, COMT) allows us to understand the different nature
      of the coupling of the environment to the reaction coordinate as a function of
      the electrostatic interaction established by the reactive subsystem. The
      transmission coefficients obtained using Grote-Hynes theory are in excellent
      agreement with molecular dynamics estimations and show that the coupling is
      higher in GNMT than in COMT. The larger friction observed in GNMT is explained on
      the basis of the interaction established by the substrate in the active site. The
      larger value of the friction leads to a smaller value of the reaction frequency
      and thus also to a larger disagreement with the estimation of the transmission
      coefficient based on the frozen environment approach.

PMID- 18085773
TI  - Synthesis, structure, and infrared spectroscopy of the first Np5+ neptunyl
      silicates, Li6(NpO2)4(H2Si2O7)(HSiO4)2(H2O)4 and K3(NpO2)3(Si2O7).
AB  - Two Np(5+) silicates, Li(6)(NpO(2))(4)(H(2)Si(2)O(7))(HSiO(4))(2)(H(2)O)(4)
      (LiNpSi1) and K(3)(NpO(2))(3)(SiO(3)OH)(2) (KNpSi1), were synthesized by
      hydrothermal methods. The crystal structures were determined using direct methods
      and refined on the basis of F(2) for all unique data collected with Mo Kalpha
      radation and an APEX II CCD detector. LiNpSi1 crystallizes in orthorhombic space
      group Pnma with a =13.189(6) A, b = 7.917(3) A, c = 10.708(5) A, V = 1118.1(8)
      A3, and Z = 2. KNpSi1 is hexagonal, P62m, a = 9.734(1) A, c = 3.8817(7) A, V =
      318.50(8) A3, and Z = 1. LiNpSi1 contains chains of edge-sharing neptunyl
      pentagonal bipyramids linked into two-dimensional sheets through direct linkages
      between the neptunyl polyhedra and the vertex sharing of the silicate tetrahedra.
      The structure contains both sorosilicate and nesosilicate units, resulting in a
      new complex neptunyl silicate sheet. KNpSi1 contains edge-sharing neptunyl square
      bipyramids linked into a framework structure through the sharing of vertices with
      the silicate tetrahedra. The neptunyl silicate framework contains channels
      approximately 6.0 A in diameter. These structures exhibit significant departures
      from other reported Np(5+) and U(6+) compounds and represent the first reported
      Np(5+) silicate structures.

PMID- 18085774
TI  - Structural phase transition of Gd3RuO7.
AB  - Structural phase transition of trigadorinium ruthenium heptaoxide, Gd(3)RuO(7),
      has been investigated by in situ high-temperature single-crystal X-ray
      diffraction. A small shrinkage in b-length and an expansion in c-length were
      observed between 363 and 383 K with increasing temperature. No significant change
      occurred in a-length within experimental errors. The changes were essentially
      reversible against temperature. Structures of the high-temperature modification
      have been determined at 423, 773, and 1223 K assuming the orthorhombic Cmcm
      symmetry. The structure of the low-temperature modification has been determined
      at 293 K, assuming the orthorhombic P2(1)nb symmetry with doubled unit cell along
      the b-axis of the high-temperature modification. The transition from high- to low
      temperature modification can be structurally characterized by tilts about axes
      close to the c-axis of the unit cell occurring on half of the RuO(6) octahedra.
      These octahedral tilts couple with a reduction in coordination number of the Gd
      atom bridging the adjacent RuO(6) single chains along the b-axis. The present
      study also revealed the presence of structural disorder in the high-temperature
      Cmcm modification that had not been reported for the archetypal Cmcm structures
      of lanthanide ruthenates (Ln(3)RuO(7)) and osmates (Ln(3)OsO(7)) in the
      literature. The disorder includes a dynamical or static distribution of one-third
      of Gd atoms in the unit cell, which is presumably linked to the libration of the
      octahedral tilts about the axes close to c.

PMID- 18085775
TI  - Antiferromagnetic behavior based on quasi-orthogonal MOs: synthesis and
      charaterization of a Cu3 oxidase model.
AB  - We report the synthesis and structural and magnetic characterization of an
      original Cu(3) oxidase model. The Schiff base ligand used in the synthesis
      derives from condensation of acetylacetone with glycine amino acid. The
      K[Cu(3)(L)(3)(micro(3)-OH)].(H(2)O)(2) complex crystallizes at room temperature
      in the tetragonal P43212 space group with a = 20.540(3) A and c = 15.866(6) A and
      consists of triangular Cu(3) units. The magnetic behavior interpretation suggests
      the presence of spin frustration, which has been investigated by means of ab
      initio DDCI calculations. It is shown that the system should be viewed as a
      "menage a trois" spin-coupled pattern mediated by a central hydroxo group,
      lifting the doublet degeneracy by approximately 8 cm-1.

PMID- 18085776
TI  - Ferrocenoyl pyridine arene ruthenium complexes with anticancer properties:
      synthesis, structure, electrochemistry, and cytotoxicity.
AB  - Organometallic ruthenium(II) complexes of general formula [Ru(eta(6)
      arene)Cl(2)(NC(5)H(4)OOC-C(5)H(4)FeC(5)H(5))], where arene = C(6)H(6) (1),
      C(6)H(5)Me (2), p-iPrC(6)H(4)Me (3), and C(6)Me(6) (4), and of general formula
      [Ru(eta(6)-arene)Cl(2)](2)(NC(5)H(4)OOC-C(5)H(4)FeC(5)H(4)-COOC(5)H(4)N), where
      arene = p-iPrC(6)H(4)Me (5) and C(6)Me(6) (6), have been synthesized and
      characterized, the molecular structures of these complexes being confirmed by
      single-crystal X-ray structure analysis of complex 4 as a representative example.
      The redox properties and in vitro anticancer activities of complexes 1-6 have
      been studied. All the compounds are moderately cytotoxic toward the A2780 and
      A2780cisR (cisplatin-resistant) human ovarian carcinoma cell lines. The
      diruthenium arene complexes 5 and 6 are about twice as active as their
      mononuclear analogues 3 and 4. Cyclic voltammetry revealed a good correlation of
      the RuII/RuIII redox potentials of 1-4 and the number of alkyl substituents in
      the arene ligand.

PMID- 18085777
TI  - Chemical synthesis of a glycoprotein having an intact human complex-type
      sialyloligosaccharide under the Boc and Fmoc synthetic strategies.
AB  - The chemical synthesis of complex glycoproteins is an ongoing challenge in
      protein chemistry. We have examined the synthesis of a single glycoform of
      monocyte chemotactic protein-3 (MCP-3), a CC-chemokine that consists of 76 amino
      acids and one N-glycosylation site. A three-segment native chemical ligation
      strategy was employed using unprotected peptides and glycopeptide. Importantly,
      the synthesis required the development of methods for the generation of
      sialylglycopeptide-alphathioesters. For the sialylglycopeptide-alphathioester
      segment, we examined and successfully implemented approaches using Fmoc-SPPS and
      Boc-SPPS. To avoid use of hydrogen fluoride, the Boc approach utilized minimal
      side chain protection and direct thiolysis of the resin bound peptide. Using
      these strategies, we successfully synthesized a glycoprotein having an intact and
      homogeneous complex-type sialyloligosaccharide.

PMID- 18085779
TI  - Mechanism and control of rare tautomer trapping at a metal-metal bond: adenine
      binding to dirhodium antitumor agents.
AB  - The cause of mutations in the genome by the occurrence of nuclebases in their
      rare tautomeric forms was first proposed by Watson and Crick in 1953. Since this
      pioneering proposal, tremendous experimental and theoretical research efforts
      have aimed to elucidate the conditions under which nucleobase tautomerizations
      can occur. Previous work raised the interesting question as to whether adenine
      binding to the anticancer drug cisplatin can induce tautomerization of the
      nucleobase, but the results indicated such an event to be unlikely under
      physiological conditions. In this work, we have studied the reaction of three
      adenine (Ade) tautomers with metal-metal bonded dirhodium antitumor agents using
      high-level computations. The calculations reveal that the thermodynamically most
      stable compound in the reaction of Ade with dirhodium tetraformate in aqueous
      solution is a species in which a rare N6-imino tautomer spans the metal-metal
      bond via sites N7 and N6. However, comprehensive transition state predictions
      suggest that the multiple-step mechanisms leading to this bridging species are
      kinetically highly challenging. A number of strategies to chemically modify the
      metal-metal unit are considered, aiming to derive a rational plan for trapping
      the rare N6-imino tautomer, which is incapable of Watson-Crick pairing with
      canonical thymine.

PMID- 18085778
TI  - Temperature triggered self-assembly of polypeptides into multivalent spherical
      micelles.
AB  - We report herein thermally responsive elastin-like polypeptides (ELPs) in a
      linear AB diblock architecture with an N-terminal peptide ligand that self
      assemble into spherical micelles when heated slightly above body temperature. A
      series of 10 ELP block copolymers (ELP(BC)'s ) with different molecular weights
      and hydrophilic-to-hydrophobic block ratios were genetically synthesized by
      recursive directional ligation. The self-assembly of these polymers from unimers
      into micelles was investigated by light scattering, fluorescence spectroscopy,
      and cryo-TEM. These ELP(BC)'s undergo two phase transitions as a function of
      solution temperature: a unimer-to-spherical micelle transition at an intermediate
      temperature and a micelle-to-bulk aggregate transition at a higher temperature
      when the hydrophilic-to-hydrophobic block ratio is between 1:2 and 2:1. The
      critical micelle temperature is controlled by the length of the hydrophobic
      block, and the size of the micelle is controlled by both the total ELP(BC) length
      and hydrophilic-to-hydrophobic block ratio. These polypeptide micelles display a
      critical micelle concentration in the range 4-8 microM demonstrating the high
      stability of these structures. These studies have also identified a subset of
      ELP(BC)'s bearing terminal peptide ligands that are capable of forming
      multivalent spherical micelles that present multiple copies of the ligand on
      their corona in the clinically relevant temperature range 37-42 degrees C and
      target cancer cells. These ELP(BC)'s may be useful for drug targeting by
      thermally triggered multivalency. More broadly, the design rules uncovered by
      this study should be applicable to the design of other thermally reversible
      nanoparticles for diverse applications in medicine and biology.

PMID- 18085782
TI  - Tri-tert-butylsilylsilylenes with alkali metal substituents ((t)Bu3Si)SiM (M =
      Li, K): electronically and sterically accessible triplet ground states.

PMID- 18085783
TI  - Fundamental electron-transfer properties of non-heme oxoiron(IV) complexes.

PMID- 18085784
TI  - Salarins a and B and tulearin a: new cytotoxic sponge-derived macrolides.
AB  - Three novel nitrogenous macrolides designated salarin A and B (1 and 2) and
      tulearin A (3) were isolated from the Madagascar Fascaplysinopsis sp. sponge. The
      structures of the compounds were elucidated by interpretation of MS and 1D and 2D
      NMR spectra. Both salarins carry an acetylcarbamate moiety, and in addition, 1
      contains a triacylamine group and 2 a methoxymethylketone lactam. Tulearin A
      carries the naturally rare carbamate ester. The compounds were found to be toxic
      to brine shrimp larvae, and salarin A and tulearin A were also cytotoxic to
      leukemia cells.

PMID- 18085785
TI  - Total synthesis of (+/-)-goniomitine via a formal nitrile/donor-acceptor
      cyclopropane [3 + 2] cyclization.
AB  - The total synthesis of (+/-)-goniomitine has been accomplished in 17 linear steps
      with 5.2% overall yield starting from commercially available delta-valerolactam.
      A synthetic highlight includes the first application of a formal [3 + 2]
      cycloaddition between a highly functionalized nitrile and a donor-acceptor
      cyclopropane to prepare an indole nucleus. The use of a microwave reactor is
      shown to greatly improve the reaction times for two steps.

PMID- 18085786
TI  - A mechanistic design principle for protein tyrosine kinase sensors: application
      to a validated cancer target.
AB  - A new mechanistic principle for reporting the phosphorylation of tyrosine is
      described, which should prove applicable to even the most fastidious of protein
      tyrosine kinases, as demonstrated by the acquisition of a fluorescent sensor for
      the extraordinarily demanding anaplastic lymphoma kinase.

PMID- 18085787
TI  - Structural effects on thermal rearrangement of fulleroids to methanofullerenes.
      The prominent role of cyclopropyl vs aryl substituent.
AB  - The kinetics of the thermal rearrangement of a series of novel cyclopropyl
      substituted [5,6] open fulleroids to the [6,6] closed methanofullerenes have been
      investigated in comparison with the aryl-substituted homologues. The cyclopropyl
      group markedly accelerated the rates due to the stereoelectronically favorable pi
      conjugative effects in the radical-like [1,5] shift of the transient [5,6] closed
      isomers, overriding the geometrically constrained aryl group.

PMID- 18085788
TI  - Stereoselective total synthesis of (-)-perrottetinene and assignment of its
      absolute configuration.
AB  - The first stereoselective total synthesis of the bibenzyl tetrahydrocannabinol, (
      )-perrottetinene, has been achieved from readily available starting materials.
      The absolute stereochemistry is derived from a chiral gamma-hydroxy
      vinylstannane. The key reaction is the synthesis of the cis-disubstituted
      cyclohexene ring of perrottetinene by diastereoselective Ireland-Claisen
      rearrangement and a ring-closing metathesis reaction. The absolute configuration
      of (-)-perrottetinene is proposed.

PMID- 18085789
TI  - Chiral N-heterocyclic carbene catalyzed staudinger reaction of ketenes with
      imines: highly enantioselective synthesis of N-Boc beta-lactams.
AB  - N-heterocyclic carbenes (NHCs) were demonstrated to be efficient catalysts for
      the Staudinger reaction of ketenes with N-tosyl, N-benzyloxycarbonyl, or N-tert
      butoxycarbonyl imines. Chiral NHC 8b, conveniently prepared from L-pyroglutamic
      acid, catalyzed the reactions of arylalkylketenes with a variety of N-tert
      butoxycarbonyl arylimines to give the corresponding cis-beta-lactams in good
      yields with good diastereoselectivities and excellent enantioselectivities (up to
      99% ee). Two possible catalytic pathways, initiated by the addition of NHC to
      ketenes or imines, were discussed.

PMID- 18085790
TI  - Effect of shear stress on anthraquinones production by Rubia tinctorum suspension
      cultures.
AB  - Suspension cultures of Rubia tinctorum, an anthraquinones (AQs) producer, were
      grown both in Erlenmeyer flasks at 100 rpm and in a 1.5 L mechanically stirred
      tank bioreactor operating at 450 rpm. The effect of hydrodynamic stress on cell
      viability, biomass, and AQs production was evaluated. Cell viability showed a
      transient decrease in the bioreactor during the first days, returning to the
      initial values toward the end of the culture time. The biomass obtained in the
      bioreactor was 29% lower than that attained in the Erlenmeyer flasks. The H2O2
      production in the bioreactor (with peaks at 7 and 10 days) was about 15 times
      higher than that obtained in the flasks. A clear relationship exists between the
      maximum concentration of H2O2 generated and AQs produced. The AQs content in the
      bioreactor was 233% higher than that in the Erlenmeyer flasks. The AQs specific
      productivity in the stirred tank and in the Erlenmeyer flasks was 70.7 and 28.5
      micromol/g FW/day, respectively. This production capability was maintained in the
      regrowth assays. On the other hand, the negative effects of hydrodynamic stress
      on viability and biomass concentration observed in the bioreactor culture were
      reverted in the regrowth cultures. It can be concluded that R. tinctorum
      suspension cultures are able to grow in stirred tanks at 450 rpm responding to
      the hydrodynamic stress with higher concentrations of AQs, which suggest the
      possibility of a technological approach taking advantage of this phenomenon.

PMID- 18085791
TI  - Preparation and synthetic applications of aryl tetraflates (ArOSO2CF2CF2H).
AB  - We have recently developed an improved synthetic route to 1,1,2,2
      tetrafluoroethanesulfonic acid (HCF2CF2SO3H, TFESA) and explored the applications
      of this newly available superacid in catalysis. Low volatility, ease of handling,
      and a convenient 1H NMR handle make this acid an attractive alternative to
      triflic acid. TFESA can also be converted to several of its derivatives:
      anhydride, sulfonyl chloride, and sulfonyl fluoride, which provide a good entry
      point for the synthesis of aryl sulfonates. We prepared several aryl esters of
      1,1,2,2-tetrafluoroethanesulfonic acid (aryl tetraflates) and showed that they
      can be used in a number of palladium-catalyzed coupling reactions (Suzuki, Heck,
      and Buchwald-Hartwig couplings). While the reactivity of tetraflates lies between
      that of triflates and chlorides, tetraflates appear to be more thermally stable.
      Additionally, the presence of a hydrogen atom in the tetraflate group facilitates
      monitoring of reactions and characterization of derivatives.

PMID- 18085792
TI  - Studies toward the synthesis of 4-(2-R-ethyl)amino-2,2,5,5-tetramethyl-3
      imidazoline 1-oxyls. nucleophilic substitution of bromide in the N-Alkyl chain of
      the 1,2,4-oxadiazol-2-one precursor.
AB  - A synthetic approach to access the new nitroxides of the amidine type exhibiting
      pH-dependent EPR spectra through substitution of a halide in the exo-N
      halogenoalkyl chain of 1-(2-bromoethyl)-6-oxyl-5,5,7,7
      tetramethyltetrahydroimidazo[1,5-b][1,2,4]oxadiazol-2-one is reported. In this
      approach, an oxycarbonyl moiety of the oxadiazolone heterocycle plays the role of
      a "protecting group" for the amidine functionality. A nucleophilic cleavage of
      the oxadiazolone heterocycle under mild nonbasic conditions, applicable to
      substrates bearing substituents vulnerable to attack by strong basic
      nucleophiles, is elaborated. The approach allows for the new amidine nitroxides
      bearing various functional groups (e.g., such as CN, N3, NH2, COOEt) to be
      synthesized. A series of nitroxides obtained through the
      Staudinger/intermolecular aza-Wittig reaction of the azido derivative is also
      described. The nitroxides synthesized here were found to have pH-dependent two
      component EPR spectra indicative of a slow, on the EPR time scale, R* left arrow
      over right arrow R*H+ chemical exchange, and pKa values ranging from 2.8 to 12.5
      units. The guanidine derivatives synthesized in this work show the highest pKa
      values (pKa = 10.2 and 12.5, respectively) ever reported for the nitroxide pH
      probes of a "basic type".

PMID- 18085793
TI  - Hexakis(4-(N-butylpyridylium))benzene: a six-electron organic redox system.
AB  - The cobalt-catalyzed cyclotrimerization of bis(4-pyridyl)acetylene affords
      hexakis(4-pyridyl)benzene in moderate yield. Alkylation with n-butyltriflate
      gives hexakis(4-(N-butylpyridylium))benzene triflate (1 6+), which can be reduced
      with Na/Hg in DMF to neutral 10. A single-crystal X-ray diffraction structure
      reveals that 1 0 has a chair-cyclohexane-like core and a [6]radialene structure.
      Cyclic voltammetry shows that 1 6+ is reversibly reduced to 1 2+ in one four
      electron step and 1 2+ is reversibly reduced to 1 0 in one two-electron step. A
      reduction by four electrons at one potential is unprecedented for a molecule in
      which the electrochemically active centers are in electronic communication. The
      large structural transformation from 1 6+ to 1 0 is responsible for the
      "potential inversion" in the cyclic voltammetry, and DFT calculations suggest a
      possible structure for the stable intermediate 1 2+. A comparison is made to the
      electrochemistry and structural transformations in a previously prepared
      [4]radialene analogue of 1 0.

PMID- 18085794
TI  - Synthesis, spectroscopy, and theoretical calculations for a series of push-pull
      [14]-pyridoannulenes.
AB  - Three new isomeric dipyridoannulenes were synthesized and characterized. These
      molecules possess differing conjugation pathways between the substituent alkoxy
      donating groups and the pyridyl acceptor groups. Optical absorption and emission
      properties of the dipyridoannulenes and their corresponding acyclic precursors
      were measured and correlated to structural differences and used to evaluate
      conjugation effectiveness and charge-transfer pathways. Optical properties of
      protonated dipyridoannulenes were also measured and found to be somewhat
      insensitive to the degree of protonation. Density functional studies of these
      systems at the B3LYP/6-31G* level provided insight into their stabilities,
      polarities, and quinoidal character. An analysis of the HOMO and LUMO molecular
      orbitals provided further information regarding charge-transfer behavior. These
      systems are good metal binding candidates, as the pyridine moiety can act as both
      an electron-acceptor and a site for metal coordination.

PMID- 18085795
TI  - A convenient synthesis of substituted pyrazolidines and azaproline derivatives
      through highly regio- and diastereoselective reduction of 2-pyrazolines.
AB  - The synthesis of substituted N-acetyl- and N-aroyl-2-pyrazolines via
      intramolecular Michael addition of alpha,beta-unsaturated hydrazones generated
      through olefination of phosphinyl and phosphonyl hydrazones with carbonyl
      compounds is reported. The regioselective reduction of the C-N double bond in
      these 2-pyrazolines using Superhydride (Et3BHLi) gives pirazolidine derivatives
      with excellent levels of cis-diastereoselectivity. These 2-pyrazolines can also
      be obtained in one-pot reaction from allenes, hydrazides, and aldehydes; and
      pyrazolidines, after reduction, from allenes, hydrazides, and aldehydes. This
      synthetic route was developed to provide a new approach to substituted azaproline
      derivatives in a diastereoselective fashion.

PMID- 18085796
TI  - Facially selective and regioselective carbometalation of cyclopropenes by aryl
      Grignard reagents.
AB  - Described is a Cu-catalyzed methodology for adding aryl Grignard reagents to 3
      hydroxymethylcyclopropene derivatives with high regio- and diastereoselectivity.
      The cyclopropylmetals can be trapped with a variety of electrophiles to generate
      highly substituted cyclopropanes.

PMID- 18085797
TI  - Antenna domain mobility and enzymatic reaction of L-rhamnulose-1-phosphate
      aldolase.
AB  - The enzyme l-rhamnulose-1-phosphate aldolase from Escherichia coli participates
      in the degradation pathway of l-rhamnose, a ubiquitous deoxy-hexose. It is a
      homotetramer of the rare C4-symmetric type with N-terminal domains protruding
      like antennas from the main body. A mobility analysis of the enzyme gave rise to
      the hypothesis that an anisotropic thermal antenna motion may support the
      catalysis (Kroemer et al., Biochemistry 42, 10560, 2003). We checked this
      hypothesis by generating four single mutants and one disulfide bridge that were
      designed to reduce the mobility of the antenna domain without disturbing the
      chain-fold or the active center. The catalytic rates of the mutants revealed
      activity reductions that correlated well with the expected antenna fixation.
      Among these mutants, K15W was crystallized, structurally elucidated, and used as
      a guide for modeling the others. The structure confirmed the design because the
      mutation introduced a tight nonpolar contact to a neighboring subunit that fixed
      the antenna but did not affect the main chain. The fixation was confirmed by a
      comparison of the anisotropic B-factors describing the mobility of the domains.
      It turned out that the distinctly anisotropic mobility of the wild-type antenna
      domain has become isotropic in K15W, in agreement with the design. We suggest
      that, like K15W, the other mutations also followed the design, validating the
      correlation between antenna mobility and activity. This correlation suggests that
      the domain mobility facilitates the reaction.

PMID- 18085798
TI  - R67, the other dihydrofolate reductase: rational design of an alternate active
      site configuration.
AB  - R67 dihydrofolate reductase (DHFR) bears no sequence or structural homologies
      with chromosomal DHFRs. The gene for this enzyme produces subunits that are 78
      amino acids long, which assemble into a homotetramer possessing 222 symmetry.
      More recently, a tandem array of four gene copies linked in-frame was
      constructed, which produces a monomer containing 312 amino acids named Quad3.
      Asymmetric mutations in Quad3 have also been constructed to probe the role of Q67
      and K32 residues in catalysis. This present study mixes and matches mutations to
      determine if the Q67H mutation, which tightens binding approximately 100-fold to
      both dihydrofolate (DHF) and NADPH, can help rescue the K32M mutation. While the
      latter mutation weakens DHF binding over 60-fold, it concurrently increases kcat
      by a factor of 5. Two Q67H mutations were added to gene copies 1 and 4 in
      conjunction with the K32M mutation in gene copies 1 and 3. Addition of these Q67H
      mutations tightens binding 40-fold, and the catalytic efficiency (kcat/Km(DHF))
      of the resulting protein is similar to that of Quad3. Since these Q67H mutations
      can mostly compensate for the K32M lesion, K32 must not be necessary for DHF
      binding. Another multimutant combines the K32M mutation in gene copies 1 and 3
      with the Q67H mutation in all gene copies. This mutant is inhibited by DHF but
      not NADPH, indicating that NADPH binds only to the wild type half of the pore,
      while DHF can bind to either the wild type or mutant half of the pore. This
      inhibition pattern contrasts with the mutant containing only the Q67H
      substitution in all four gene copies, which is severely inhibited by both NADPH
      and substrate. Since gene duplication and divergence are evolutionary tools for
      gaining function, these constructs are a first step toward building preferences
      for NADPH and DHF in each half of the active site pore of this primitive enzyme.

PMID- 18085800
TI  - Effect of reversed heme orientation on circular dichroism and cooperative oxygen
      binding of human adult hemoglobin.
AB  - We found that recombinant human adult hemoglobin (rHb A) expressed in Escherichia
      coli showed heterogeneity of components with the intensity of a positive CD band
      at 260 nm and that it could be resolved into three components (SP-1, SP-2, and SP
      3) by SP-Sepharose column chromatography. 1H NMR revealed that SP-1 is identical
      with native Hb A, while SP-2 and SP-3 largely contain the reversed heme isomer in
      both the alpha and beta subunits, with contents of approximately 50 and >80% in
      SP-2 and SP-3, respectively. Rotation of the heme 180 degrees about the 5,15-meso
      axis (reversed heme) causes an interexchange of the methyl groups at positions 2
      and 7 with the vinyl groups at positions 8 and 3, respectively. To examine the
      effect of the modification of the heme-protein contact on the structure and
      function of Hb A, we compared the 1H NMR, CD, and oxygen binding properties of
      the three components with those of native Hb A. Native Hb A exhibits a distinct
      positive CD band in both the near-UV and Soret regions, but rHb A with reversed
      heme exhibits a very weak positive CD band at 260 nm and a prominent negative CD
      band in the Soret region. Cooperativity, as measured by Hill's n value, decreased
      from 3.18 (SP-1) to 2.94 (SP-2) to 2.63 (SP-3) with an increase in the reversed
      heme orientation. The effect of an allosteric effector, inositol hexaphosphate
      (IHP), on the oxygen binding properties was also reduced in rHb A with reversed
      heme. These results indicate that changes in the heme-globin contact exert a
      discernible influence on CD spectra and cooperative oxygen binding.

PMID- 18085801
TI  - Effects of graft densities and chain lengths on separation of bioactive compounds
      by nanolayered thermoresponsive polymer brush surfaces.
AB  - We have prepared various poly(N-isopropylacrylamide) (PIPAAm)-grafted silica bead
      surfaces through surface-initiated atom transfer radical polymerization (ATRP) by
      changing graft densities and brush chain lengths. The prepared surfaces were
      characterized by chromatographic analysis using the modified silica beads as
      chromatographic stationary phases. ATRP initiator (2-(m,p
      chloromethylphenyl)ethyltrichlorosilane) density on silica bead surfaces was
      modulated by changing the feed composition of the self-assembled monolayers
      (SAMs) of mixed silane coupling agents consisting of ATRP initiator and
      phenethyltrichlorosilane on the surfaces. IPAAm was then polymerized on SAM
      modified silica bead surfaces by ATRP in 2-propanol at 25 degrees C. The chain
      length of the grafted PIPAAm was controlled by simply changing the ATRP reaction
      time at constant catalyst concentration. The thermoresponsive surface properties
      of the PIPAAm-grafted silica beads were investigated by temperature-dependent
      elution behavior of hydrophobic steroids from the surfaces using Milli-Q water as
      a mobile phase. On the surfaces grafted with shorter PIPAAm chains, longer
      retention times for steroids were observed on sparsely grafted PIPAAm surfaces
      compared to dense PIPAAm brushes at low temperature, because of hydrophobic
      interactions between the exposed phenethyl groups of SAMs on silica surfaces and
      steroid molecules. Retention times for steroids on dilute PIPAAm chain columns
      decreased with temperature similarly to conventional reverse-phase
      chromatographic modes on octadecyl columns. This effect was due to limited
      interaction of solutes with the PIPAAm-grafted surfaces. Retention times for
      steroids on dilute PIPAAm brush surfaces with longer PIPAAm chains became greater
      above the PIPAAm transition temperature. At low-temperature regions, hydrated and
      expanded PIPAAm at low temperatures prevented hydrophobic interactions between
      the phenethyl group of SAMs on the silica bead surfaces and steroid molecules.
      Retention times for steroids on a dense PIPAAm brush column increased with
      temperature since solvated polymer segments within the dense brush layer undergo
      dehydration over a broad range of temperatures. In conclusion, PIPAAm graft
      density has a crucial influence on the elution behavior of steroids because of
      the interaction of analytes with silica bead interfaces, and because of the
      characteristic dehydration of PIPAAm in dense-pack brush surfaces.

PMID- 18085799
TI  - Isolevuglandin-modified proteins, including elevated levels of inactive calpain
      1, accumulate in glaucomatous trabecular meshwork.
AB  - We report that protein adducts of iso[4]levuglandin E2 (iso[4]LGE2), a highly
      reactive product of free radical-induced lipid oxidation, accumulate in human
      glaucomatous trabecular meshwork (TM) but not in controls. Reactive oxygen
      species play a pathogenic role in primary open angle glaucoma by fostering
      changes that reduce permeability of the TM tissue and consequently impede aqueous
      humor outflow resulting in elevated intraocular pressure. IsoLGs covalently
      modify proteins and are especially effective in causing protein-protein cross
      linking. We found elevated levels of calpain-1 in glaucomatous TM. However,
      calpain activity in glaucomatous TM is only about 50% of that in controls. This
      paradox is explicable by the fact that modification by isoLGs renders calpain-1
      inactive. Thus, treatment of calpain-1 with iso[4]LGE2 in vitro results in
      covalent modification, inactivation, the formation of high molecular weight
      aggregates (as determined by Western and dynamic light scattering analyses), and
      resistance to proteasomal digestion. Iso[4]LGE2-modified calpain-1 undergoes
      ubiquitination, and its loading impairs the cellular proteasome activity,
      consistent with competitive inhibition and formation of suicidal high molecular
      weight aggregates. These data suggest that interference with proteasomal
      activity, owing to protein modification by isoLGs, could contribute to glaucoma
      pathophysiology by decreasing the ability of the TM to modulate outflow
      resistance.

PMID- 18085802
TI  - Friction of fatty acids in nanometer-sized contacts of different adhesive
      strength.
AB  - The effects of adhesion, contact area, and pressure on the lubricating properties
      of self-assembled monolayers on steel have been investigated with friction force
      microscopy. The adsorbed molecules were fatty acids with varying degrees of
      unsaturation (0-2 double bonds; stearic, oleic, and linoleic acid) and a rosin
      acid (dehydroabietic acid), adsorbed from n-hexadecane solution. The friction of
      these loose-packed monolayers was studied in dry N2 gas and in ethanol. Low
      adhesion (in ethanol) resulted in a linear increase in friction force at low
      loads, that is, F = muL, whereas higher adhesion (in N2 gas) gave an apparent
      area-dependence at low loads of the form F = S(c)A, where S(c) is the critical
      shear stress. A recent model for the contact mechanics of a compliant elastic
      film confined between stiffer substrates was applied to the data obtained in dry
      N2. Using this approach, we obtained interfacial energies of the compliant
      monolayers in good agreement with van der Waals-Lifshitz theory. With a low
      monolayer elastic modulus of E'(1)=0.2 GPa, we obtained a slightly higher value
      of Sc for stearic acid than that established for more close-packed stearic acid
      monolayers. An increase of mu and S(c) was found with increasing degree of
      unsaturation of the fatty acid.

PMID- 18085803
TI  - Electrophoresis of a colloidal sphere in a spherical cavity with arbitrary zeta
      potential distributions and arbitrary double-layer thickness.
AB  - The electrophoretic motion of a dielectric sphere situated at the center of a
      spherical cavity with an arbitrary thickness of the electric double layers
      adjacent to the particle and cavity surfaces is analyzed at the quasisteady state
      when the zeta potentials associated with the solid surfaces are arbitrarily
      nonuniform. Through the use of the multipole expansions of the zeta potentials
      and the linearized Poisson-Boltzmann equation, the equilibrium double-layer
      potential distribution and its perturbation caused by the applied electric field
      are separately solved. The modified Stokes equations governing the fluid velocity
      field are dealt with using a generalized reciprocal theorem, and explicit
      formulas for the electrophoretic and angular velocities of the particle valid for
      all values of the particle-to-cavity size ratio are obtained. To apply these
      formulas, one only has to calculate the monopole, dipole, and quadrupole moments
      of the zeta potential distributions at the particle and cavity surfaces. In some
      limiting cases, our result reduces to the analytical solutions available in the
      literature. In general, the boundary effect on the electrophoretic motion of the
      particle is a qualitatively and quantitatively sensible function of the thickness
      of the electric double layers relative to the radius of the cavity.

PMID- 18085804
TI  - Adsorption of C60 buckminster fullerenes on an 11-amino-1-undecene-covered
      Si(111) substrate.
AB  - Buckminster fullerene C60 was used as a model to understand the attachment
      chemistry of large molecules on amine-terminated self-assembled monolayers (SAM)
      on semiconductor substrates. This type of interface serves as a prototype for
      future devices in such fields as solar energy conversion, biosensing, catalysis,
      and molecular electronics. Fullerene C60 was attached to 11-amino-1-undecene self
      assembled monolayers on a Si(111) surface. The chemical state and topography of
      the C60-modified surface were characterized by surface analytical spectroscopic
      and microscopic methods and by computational investigation. X-ray photoelectron
      spectroscopy revealed that the secondary amine group is formed between the C60
      and the 11-amino-1-undecene SAM on the surface. The appearance of the pi-pi* C 1s
      shakeup peak confirmed the presence of C60 on the surface. Infrared spectroscopic
      studies verified several characteristic features of the C60 skeleton vibration
      and the 11-amino-1-undecene vibrational signature. The atomic force microscopy
      investigation suggested that the fullerene molecules produce surface features
      with an apparent height of approximately 2 nm and an average width of
      approximately 20 nm. A parallel study was performed on a Au(111) surface for
      comparison with the results obtained on the silicon substrate. The reaction
      between fullerene molecules and approximately 1% 11-amino-1-undecene diluted in
      decene SAM on the Si(111) surface accordingly yielded dilute and uniformly
      distributed C60 molecules on the surface, which indicated that the amine groups
      were the reactive sites.

PMID- 18085805
TI  - Incorporation of alpha-hemolysin in different tethered bilayer lipid membrane
      architectures.
AB  - Tethered bilayer lipid membranes are stable solid supported model membrane
      systems. They can be used to investigate the incorporation and function of
      membrane proteins. In order to study ion translocation mediated via incorporated
      proteins, insulating membranes are necessary. The architecture of the membrane
      can have an important effect on both the electrical properties of the lipid
      bilayer as well as on the possibility to functionally host proteins. Alpha
      hemolysin pores have been functionally incorporated into a tethered bilayer lipid
      membrane coupled to a gold electrode. The protein incorporation has been
      monitored optically and electrically and the influence of the molecular structure
      of the anchor lipids on the insertion properties has been investigated.

PMID- 18085806
TI  - Electronic transport in single molecule junctions: control of the molecule
      electrode coupling through intramolecular tunneling barriers.
AB  - We report on single molecule electron transport measurements of two
      oligophenylenevinylene (OPV3) derivatives placed in a nanogap between gold (Au)
      or lead (Pb) electrodes in a field effect transistor device. Both derivatives
      contain thiol end groups that allow chemical binding to the electrodes. One
      derivative has additional methylene groups separating the thiols from the
      delocalized pi-electron system. The insertion of methylene groups changes the
      open state conductance by 3-4 orders of magnitude and changes the transport
      mechanism from a coherent regime with finite zero-bias conductance to sequential
      tunneling and Coulomb blockade behavior.

PMID- 18085807
TI  - Alkali-metal-induced enhancement of hydrogen adsorption in C60 fullerene: an ab
      Initio study.
AB  - It is demonstrated that the doping of alkali metal atoms on fullerene, C60,
      remarkably enhances the molecular hydrogen adsorption capacity of fullerenes,
      which is higher than that of conventionally known other fullerene complexes. This
      effect is observed to be more pronounced for sodium than lithium atom. The
      formation of stable complex forms of a sodium-doped fullerene molecule, Na8C60,
      and the corresponding hydrogenated species, [Na(H2)6]8C60, with 48 hydrogen
      molecules has been demonstrated to lead to a hydrogen adsorption density of
      approximately 9.5 wt %. One of the main factors favoring the interactions
      involved is attributed to the pronounced charge transfer from the sodium atom to
      the C60 molecule and electrostatic interaction between the ion and the
      dihydrogen. The suitability of these complexes for developing fullerene-based
      hydrogen storage materials is discussed.

PMID- 18085808
TI  - Electronic structure tailoring and selective adsorption mechanism of metal-coated
      nanotubes.
AB  - Effects of various metal coating (Co, Ti, Pd, W, and Ru) on electronic structures
      of carbon nanotubes are systematically studied by both ab initio calculations and
      field-emission experiments. The theoretical results indicate that the adsorption
      of metal atoms leads to substantial changes in the band structures and work
      functions of nanotubes. In particular, titanium is found to be the most effective
      coating material for the application of nanotubes to the field emission display,
      by lowering the work function and increasing the local density of states near the
      Fermi level. This is confirmed by the field-emission experiments using Ti-coated
      nanotubes, which shows enhanced emission performances. In addition, it is found
      that the Ti coating extends the lifetime of the nanotube substantially. Through
      the thermogravimetric analysis and theoretical modeling, we propose that this is
      related to the role of metal coating as a protection layer against residual gases
      such as oxygen, which cause the degradation of nanotubes. The applications of
      metal-coated nanotubes to other types of electronic devices are also discussed.

PMID- 18085809
TI  - Approximate analytical models for phonon specific heat and ballistic thermal
      conductance of nanowires.
AB  - We introduce simple approximate analytical models for phonon specific heat and
      ballistic thermal conductance of nanowires. The analytical model is in excellent
      agreement with the detailed numerical calculations based on the solution of the
      elastic wave equation and is also in good agreement with the ballistic thermal
      conductance data by Schwab et al. (Nature 2000, 404, 974). Finally, we propose a
      demarcating criterion in terms of temperature, dimension, and material properties
      to capture the dimensional crossover from a three-dimensional (3D) bulk system to
      a one-dimensional (1D) system.

PMID- 18085810
TI  - Highly responsive hydrogel scaffolds formed by three-dimensional organization of
      microgel nanoparticles.
AB  - We present a robust and straightforward method for fabricating remarkably
      responsive hydrogel scaffolds consisting of submicron-sized microgel particles.
      We demonstrate that the microgel particles assemble either through bridging or
      depletion interactions to yield a structure that swells or deswells at a
      macroscopic level in much shorter times as compared to a bulk polymer gel of
      similar characteristics. This approach offers a new way of fabricating functional
      hydrogel scaffolds with controllable responsiveness to applied stimuli and
      excellent loading capability for a wide variety of materials, irrespective of
      chemistry, size, and shape.

PMID- 18085811
TI  - Molecular doping of graphene.
AB  - Graphene is considered as one of the most promising materials for post silicon
      electronics, as it combines high electron mobility with atomic thickness
      [Novoselov et al. Science 2004, 306, 666-669. Novoselov et al. Proc. Natl. Acad.
      Sci. U.S.A. 2005, 102, 10451-10453]. The possibility of chemical doping and
      related excellent chemical sensor properties of graphene have been demonstrated
      experimentally [Schedin et al. Nat. Mater. 2007, 6, 652-655], but a microscopic
      understanding of these effects has been lacking, so far. In this letter, we
      present the first joint experimental and theoretical investigation of adsorbate
      induced doping of graphene. A general relation between the doping strength and
      whether adsorbates are open- or closed-shell systems is demonstrated with the NO2
      system: The single, open shell NO2 molecule is found to be a strong acceptor,
      whereas its closed shell dimer N2O4 causes only weak doping. This effect is
      pronounced by graphene's peculiar density of states (DOS), which provides an
      ideal situation for model studies of doping effects in semiconductors. We show
      that this DOS is ideal for "chemical sensor" applications and explain the
      recently observed [Schedin et al. Nat. Mater. 2007, 6, 652-655] NO2 single
      molecule detection.

PMID- 18085812
TI  - Piezoelectric potential output from ZnO nanowire functionalized with p-type
      oligomer.
AB  - We have studied the piezoelectric potential output of a ZnO wire/belt
      functionalized with p-type oligomer (2,5-Bis(octanoxy)-1,4-bis(4-formyl phenylene
      vinylene) benzene) (OPV2) when it was deflected by an atomic force microscope
      (AFM) tip in contact mode. In comparison to the ZnO wire/belt without oligomer
      coating, an extra positive voltage peak was observed prior to the appearance of a
      negative potential peak. The paired positive and negative voltage peaks are the
      results of tip contact to the stretched and the compressed side of the wire/belt,
      corresponding to the positive and negative local piezoelectric potential,
      respectively. The p-n junction between OPV2 and ZnO serves as a "diode" that
      controls the flow of current. When the nanowire/nanobelt is first bent by the AFM
      tip, the diode is reversely biased and the piezoelectric charges are stored in
      the ZnO wire/belt. As the AFM tip further bends the wire/belt, the local
      piezoelectric potential is continuously accumulated to a value that is large
      enough to break through the diode. Then the free charges from the external
      circuit can flow in and neutralize/screen part of the piezoelectric charges,
      resulting in a positive pulse in the output signal. When the AFM tip continues to
      scan to reach the compressed side of the ZnO wire/belt, the p-n junction is
      forwardly biased. Neutralizing/screening the residual and the newly created
      piezoelectric charges leads to the flow of current from the tip to the ZnO
      wire/belt, resulting in a negative voltage pulse. This study supports the
      charging and discharging model proposed for the piezoelectric nanogenerator.

PMID- 18085813
TI  - Electronically controlled surface plasmon dispersion and optical transmission
      through metallic hole arrays using liquid crystal.
AB  - The enhanced optical properties of metal films periodically perforated with an
      array of sub-wavelength size holes have recently been widely studied in the field
      of surface plasmon optics. The ability to design the optical transmission of such
      nanostructures, which act as plasmonic crystals, by varying their geometrical
      parameters gives them great flexibility for numerous applications in photonics,
      opto-electronics, and sensing. Transforming these passive optical elements into
      devices that may be actively controlled has presented a new challenge. Here, we
      report on the realization of an electrically controlled nanostructured optical
      system based on the unique properties of surface plasmon polaritonic crystals in
      contact with a liquid crystal (LC) layer. We discuss the effect of LC layer
      modulation on the surface plasmon dispersion, the related optical transmission
      and the underlying mechanism. The reported effect may be used to achieve active
      spectral tuneability and switching in a wide range of applications.

PMID- 18085814
TI  - Carrier density and Schottky barrier on the performance of DC nanogenerator.
AB  - By assembling a ZnO nanowire (NW) array based nanogenerator (NG) that is
      transparent to UV light, we have investigated the performance of the NG by tuning
      its carrier density and the characteristics of the Schottky barrier at the
      interface between the metal electrode and the NW. The formation of a Schottky
      diode at the interface is a must for the effective operation of the NG. UV light
      not only increases the carrier density in ZnO but also reduces the barrier
      height. A reduced barrier height greatly weakens the function of the barrier for
      preserving the piezoelectric potential in the NW for an extended period of time,
      resulting in little output current. An increased carrier density speeds up the
      rate at which the piezoelectric charges are screened/neutralized, but a very low
      carrier density prevents the flow of current through the NWs. Therefore, there is
      an optimum conductance of the NW for maximizing the output of the NG. Our study
      provides solid evidence to further prove the mechanism proposed for the
      piezoelectric NG and piezotronics. The output current density of the NG has been
      improved to 8.3 microA/cm2.

PMID- 18085816
TI  - Coincidence detection of place and temporal context in a network model of spiking
      hippocampal neurons.
AB  - Recent advances in single-neuron biophysics have enhanced our understanding of
      information processing on the cellular level, but how the detailed properties of
      individual neurons give rise to large-scale behavior remains unclear. Here, we
      present a model of the hippocampal network based on observed biophysical
      properties of hippocampal and entorhinal cortical neurons. We assembled our model
      to simulate spatial alternation, a task that requires memory of the previous path
      through the environment for correct selection of the current path to a reward
      site. The convergence of inputs from entorhinal cortex and hippocampal region CA3
      onto CA1 pyramidal cells make them potentially important for integrating
      information about place and temporal context on the network level. Our model
      shows how place and temporal context information might be combined in CA1
      pyramidal neurons to give rise to splitter cells, which fire selectively based on
      a combination of place and temporal context. The model leads to a number of
      experimentally testable predictions that may lead to a better understanding of
      the biophysical basis of information processing in the hippocampus.

PMID- 18085817
TI  - The Per2 negative feedback loop sets the period in the mammalian circadian clock
      mechanism.
AB  - Processes that repeat in time, such as the cell cycle, the circadian rhythm, and
      seasonal variations, are prevalent in biology. Mathematical models can represent
      our knowledge of the underlying mechanisms, and numerical methods can then
      facilitate analysis, which forms the foundation for a more integrated
      understanding as well as for design and intervention. Here, the intracellular
      molecular network responsible for the mammalian circadian clock system was
      studied. A new formulation of detailed sensitivity analysis is introduced and
      applied to elucidate the influence of individual rate processes, represented
      through their parameters, on network functional characteristics. One of four
      negative feedback loops in the model, the Per2 loop, was uniquely identified as
      most responsible for setting the period of oscillation; none of the other
      feedback loops were found to play as substantial a role. The analysis further
      suggested that the activity of the kinases CK1delta and CK1varepsilon were well
      placed within the network such that they could be instrumental in implementing
      short-term adjustments to the period in the circadian clock system. The numerical
      results reported here are supported by previously published experimental data.

PMID- 18085818
TI  - Comparative genomics search for losses of long-established genes on the human
      lineage.
AB  - Taking advantage of the complete genome sequences of several mammals, we
      developed a novel method to detect losses of well-established genes in the human
      genome through syntenic mapping of gene structures between the human, mouse, and
      dog genomes. Unlike most previous genomic methods for pseudogene identification,
      this analysis is able to differentiate losses of well-established genes from
      pseudogenes formed shortly after segmental duplication or generated via
      retrotransposition. Therefore, it enables us to find genes that were inactivated
      long after their birth, which were likely to have evolved nonredundant biological
      functions before being inactivated. The method was used to look for gene losses
      along the human lineage during the approximately 75 million years (My) since the
      common ancestor of primates and rodents (the euarchontoglire crown group). We
      identified 26 losses of well-established genes in the human genome that were all
      lost at least 50 My after their birth. Many of them were previously characterized
      pseudogenes in the human genome, such as GULO and UOX. Our methodology is highly
      effective at identifying losses of single-copy genes of ancient origin, allowing
      us to find a few well-known pseudogenes in the human genome missed by previous
      high-throughput genome-wide studies. In addition to confirming previously known
      gene losses, we identified 16 previously uncharacterized human pseudogenes that
      are definitive losses of long-established genes. Among them is ACYL3, an ancient
      enzyme present in archaea, bacteria, and eukaryotes, but lost approximately 6 to
      8 Mya in the ancestor of humans and chimps. Although losses of well-established
      genes do not equate to adaptive gene losses, they are a useful proxy to use when
      searching for such genetic changes. This is especially true for adaptive losses
      that occurred more than 250,000 years ago, since any genetic evidence of the
      selective sweep indicative of such an event has been erased.

PMID- 18085819
TI  - Animal cell differentiation patterns suppress somatic evolution.
AB  - Cell differentiation in multicellular organisms has the obvious function during
      development of creating new cell types. However, in long-lived organisms with
      extensive cell turnover, cell differentiation often continues after new cell
      types are no longer needed or produced. Here, we address the question of why this
      is true. It is believed that multicellular organisms could not have arisen or
      been evolutionarily stable without possessing mechanisms to suppress somatic
      selection among cells within organisms, which would otherwise disrupt organismal
      integrity. Here, we propose that one such mechanism is a specific pattern of
      ongoing cell differentiation commonly found in metazoans with cell turnover,
      which we call "serial differentiation." This pattern involves a sequence of
      differentiation stages, starting with self-renewing somatic stem cells and
      proceeding through several (non-self-renewing) transient amplifying cell stages
      before ending with terminally differentiated cells. To test the hypothesis that
      serial differentiation can suppress somatic evolution, we used an agent-based
      computer simulation of cell population dynamics and evolution within tissues. The
      results indicate that, relative to other, simpler patterns, tissues organized
      into serial differentiation experience lower rates of detrimental cell-level
      evolution. Self-renewing cell populations are susceptible to somatic evolution,
      while those that are not self-renewing are not. We find that a mutation
      disrupting differentiation can create a new self-renewing cell population that is
      vulnerable to somatic evolution. These results are relevant not only to
      understanding the evolutionary origins of multicellularity, but also the causes
      of pathologies such as cancer and senescence in extant metazoans, including
      humans.

PMID- 18085820
TI  - Receptor-binding and oncogenic properties of polyoma viruses isolated from feral
      mice.
AB  - Laboratory strains of the mouse polyoma virus differ markedly in their abilities
      to replicate and induce tumors in newborn mice. Major determinants of
      pathogenicity lie in the sialic binding pocket of the major capsid protein Vp1
      and dictate receptor-binding properties of the virus. Substitutions at two sites
      in Vp1 define three prototype strains, which vary greatly in pathogenicity. These
      strains replicate in a limited fashion and induce few or no tumors, cause a
      disseminated infection leading to the development of multiple solid tumors, or
      replicate and spread acutely causing early death. This investigation was
      undertaken to determine the Vp1 type(s) of new virus isolates from naturally
      infected mice. Compared with laboratory strains, truly wild-type viruses are
      constrained with respect to their selectivity and avidity of binding to cell
      receptors. Fifteen of 15 new isolates carried the Vp1 type identical to that of
      highly tumorigenic laboratory strains. Upon injection into newborn laboratory
      mice, the new isolates induced a broad spectrum of tumors, including ones of
      epithelial as well as mesenchymal origin. Though invariant in their Vp1 coding
      sequences, these isolates showed considerable variation in their regulatory
      sequences. The common Vp1 type has two essential features: 1) failure to
      recognize "pseudoreceptors" with branched chain sialic acids binding to which
      would attenuate virus spread, and 2) maintenance of a hydrophobic contact with
      true receptors bearing a single sialic acid, which retards virus spread and
      avoids acute and potentially lethal infection of the host. Conservation of these
      receptor-binding properties under natural selection preserves the oncogenic
      potential of the virus. These findings emphasize the importance of immune
      protection of neonates under conditions of natural transmission.

PMID- 18085821
TI  - A cellular basis for Wolbachia recruitment to the host germline.
AB  - Wolbachia are among the most widespread intracellular bacteria, carried by
      thousands of metazoan species. The success of Wolbachia is due to efficient
      vertical transmission by the host maternal germline. Some Wolbachia strains
      concentrate at the posterior of host oocytes, which promotes Wolbachia
      incorporation into posterior germ cells during embryogenesis. The molecular basis
      for this localization strategy is unknown. Here we report that the wMel Wolbachia
      strain relies upon a two-step mechanism for its posterior localization in
      oogenesis. The microtubule motor protein kinesin-1 transports wMel toward the
      oocyte posterior, then pole plasm mediates wMel anchorage to the posterior
      cortex. Trans-infection tests demonstrate that factors intrinsic to Wolbachia are
      responsible for directing posterior Wolbachia localization in oogenesis. These
      findings indicate that Wolbachia can direct the cellular machinery of host
      oocytes to promote germline-based bacterial transmission. This study also
      suggests parallels between Wolbachia localization mechanisms and those used by
      other intracellular pathogens.

PMID- 18085822
TI  - Co-circulation and evolution of polioviruses and species C enteroviruses in a
      district of Madagascar.
AB  - Between October 2001 and April 2002, five cases of acute flaccid paralysis (AFP)
      associated with type 2 vaccine-derived polioviruses (VDPVs) were reported in the
      southern province of the Republic of Madagascar. To determine viral factors that
      favor the emergence of these pathogenic VDPVs, we analyzed in detail their
      genomic and phenotypic characteristics and compared them with co-circulating
      enteroviruses. These VDPVs appeared to belong to two independent recombinant
      lineages with sequences from the type 2 strain of the oral poliovaccine (OPV) in
      the 5'-half of the genome and sequences derived from unidentified species C
      enteroviruses (HEV-C) in the 3'-half. VDPV strains showed characteristics similar
      to those of wild neurovirulent viruses including neurovirulence in poliovirus
      receptor transgenic mice. We looked for other VDPVs and for circulating
      enteroviruses in 316 stools collected from healthy children living in the small
      area where most of the AFP cases occurred. We found vaccine PVs, two VDPVs
      similar to those found in AFP cases, some echoviruses, and above all, many
      serotypes of coxsackie A viruses belonging to HEV-C, with substantial genetic
      diversity. Several coxsackie viruses A17 and A13 carried nucleotide sequences
      closely related to the 2C and the 3D(pol) coding regions of the VDPVs,
      respectively. There was also evidence of multiple genetic recombination events
      among the HEV-C resulting in numerous recombinant genotypes. This indicates that
      co-circulation of HEV-C and OPV strains is associated with evolution by
      recombination, resulting in unexpectedly extensive viral diversity in small human
      populations in some tropical regions. This probably contributed to the emergence
      of recombinant VDPVs. These findings give further insight into viral ecosystems
      and the evolutionary processes that shape viral biodiversity.

PMID- 18085823
TI  - Hemophagocytic macrophages harbor Salmonella enterica during persistent
      infection.
AB  - Salmonella enterica subspecies can establish persistent, systemic infections in
      mammals, including human typhoid fever. Persistent S. enterica disease is
      characterized by an initial acute infection that develops into an asymptomatic
      chronic infection. During both the acute and persistent stages, the bacteria
      generally reside within professional phagocytes, usually macrophages. It is
      unclear how salmonellae can survive within macrophages, cells that evolved, in
      part, to destroy pathogens. Evidence is presented that during the establishment
      of persistent murine infection, macrophages that contain S. enterica serotype
      Typhimurium are hemophagocytic. Hemophagocytic macrophages are characterized by
      the ingestion of non-apoptotic cells of the hematopoietic lineage and are a
      clinical marker of typhoid fever as well as certain other infectious and genetic
      diseases. Cell culture assays were developed to evaluate bacterial survival in
      hemophagocytic macrophages. S. Typhimurium preferentially replicated in
      macrophages that pre-phagocytosed viable cells, but the bacteria were killed in
      macrophages that pre-phagocytosed beads or dead cells. These data suggest that
      during persistent infection hemophagocytic macrophages may provide S. Typhimurium
      with a survival niche.

PMID- 18085824
TI  - ZEB1 regulates the latent-lytic switch in infection by Epstein-Barr virus.
AB  - The immediate-early (IE) BZLF1 gene of Epstein-Barr virus (EBV) regulates the
      switch between latent and lytic infection by EBV. We previously showed that the
      cellular transcription factor ZEB1 binds to a sequence element, ZV, located at nt
      -17 to -12 relative to the transcription initiation site of the BZLF1 promoter,
      Zp, repressing transcription from Zp in a transient transfection assay. Here, we
      report the phenotype in the context of a whole EBV genome of a variant of EBV
      strain B95.8 containing a 2-bp substitution mutation in the ZV element of Zp that
      reduced, but did not eliminate, ZEB1 binding to Zp. Strikingly, epithelial 293
      cells latently infected with the EBV ZV mutant spontaneously produced IE-, early
      , and late-gene products and infectious virus, while wild-type (WT)-infected 293
      cells did not and have never been reported to do so. Furthermore, treatment with
      the chemical inducers sodium butyrate and 12-O-tetradecanoyl-phorbol-13-acetate
      (TPA) led to an additional order-of-magnitude production of infectious virus in
      the ZV mutant-infected 293 cells, but still no virus in the WT-infected 293
      cells. Similarly, ZV mutant-infected Burkitt's lymphoma BJAB cells accumulated at
      least 10-fold more EBV IE mRNAs than did WT-infected BJAB cells, with TPA or
      sodium butyrate treatment leading to an additional 5- to 10-fold accumulation of
      EBV IE mRNAs in the ZV mutant-infected cells. Thus, we conclude that ZEB1 binding
      to Zp plays a central role in regulating the latent-lytic switch in EBV-infected
      epithelial and B cells, suggesting ZEB1 as a target for lytic-induction therapies
      in EBV-associated malignancies.

PMID- 18085826
TI  - Entropy explains aging, genetic determinism explains longevity, and undefined
      terminology explains misunderstanding both.

PMID- 18085825
TI  - Most Caenorhabditis elegans microRNAs are individually not essential for
      development or viability.
AB  - MicroRNAs (miRNAs), a large class of short noncoding RNAs found in many plants
      and animals, often act to post-transcriptionally inhibit gene expression. We
      report the generation of deletion mutations in 87 miRNA genes in Caenorhabditis
      elegans, expanding the number of mutated miRNA genes to 95, or 83% of known C.
      elegans miRNAs. We find that the majority of miRNAs are not essential for the
      viability or development of C. elegans, and mutations in most miRNA genes do not
      result in grossly abnormal phenotypes. These observations are consistent with the
      hypothesis that there is significant functional redundancy among miRNAs or among
      gene pathways regulated by miRNAs. This study represents the first comprehensive
      genetic analysis of miRNA function in any organism and provides a unique,
      permanent resource for the systematic study of miRNAs.

PMID- 18085827
TI  - A bacterial kind of aging.

PMID- 18085828
TI  - Chromosome structuring limits genome plasticity in Escherichia coli.
AB  - Chromosome organizations of related bacterial genera are well conserved despite a
      very long divergence period. We have assessed the forces limiting bacterial
      genome plasticity in Escherichia coli by measuring the respective effect of
      altering different parameters, including DNA replication, compositional skew of
      replichores, coordination of gene expression with DNA replication, replication
      associated gene dosage, and chromosome organization into macrodomains.
      Chromosomes were rearranged by large inversions. Changes in the compositional
      skew of replichores, in the coordination of gene expression with DNA replication
      or in the replication-associated gene dosage have only a moderate effect on cell
      physiology because large rearrangements inverting the orientation of several
      hundred genes inside a replichore are only slightly detrimental. By contrast,
      changing the balance between the two replication arms has a more drastic effect,
      and the recombinational rescue of replication forks is required for cell
      viability when one of the chromosome arms is less than half than the other one.
      Macrodomain organization also appears to be a major factor restricting chromosome
      plasticity, and two types of inverted configurations severely affect the cell
      cycle. First, the disruption of the Ter macrodomain with replication forks
      merging far from the normal replichore junction provoked chromosome segregation
      defects. The second major problematic configurations resulted from inversions
      between Ori and Right macrodomains, which perturb nucleoid distribution and early
      steps of cytokinesis. Consequences for the control of the bacterial cell cycle
      and for the evolution of bacterial chromosome configuration are discussed.

PMID- 18085829
TI  - Genome-wide analysis of Rad52 foci reveals diverse mechanisms impacting
      recombination.
AB  - To investigate the DNA damage response, we undertook a genome-wide study in
      Saccharomyces cerevisiae and identified 86 gene deletions that lead to increased
      levels of spontaneous Rad52 foci in proliferating diploid cells. More than half
      of the genes are conserved across species ranging from yeast to humans. Along
      with genes involved in DNA replication, repair, and chromatin remodeling, we
      found 22 previously uncharacterized open reading frames. Analysis of
      recombination rates and synthetic genetic interactions with rad52Delta suggests
      that multiple mechanisms are responsible for elevated levels of spontaneous Rad52
      foci, including increased production of recombinogenic lesions, sister chromatid
      recombination defects, and improper focus assembly/disassembly. Our cell
      biological approach demonstrates the diversity of processes that converge on
      homologous recombination, protect against spontaneous DNA damage, and facilitate
      efficient repair.

PMID- 18085830
TI  - Sustained post-mating response in Drosophila melanogaster requires multiple
      seminal fluid proteins.
AB  - Successful reproduction is critical to pass genes to the next generation. Seminal
      proteins contribute to important reproductive processes that lead to
      fertilization in species ranging from insects to mammals. In Drosophila, the
      male's accessory gland is a source of seminal fluid proteins that affect the
      reproductive output of males and females by altering female post-mating behavior
      and physiology. Protein classes found in the seminal fluid of Drosophila are
      similar to those of other organisms, including mammals. By using RNA interference
      (RNAi) to knock down levels of individual accessory gland proteins (Acps), we
      investigated the role of 25 Acps in mediating three post-mating female responses:
      egg production, receptivity to remating and storage of sperm. We detected roles
      for five Acps in these post-mating responses. CG33943 is required for full
      stimulation of egg production on the first day after mating. Four other Acps
      (CG1652, CG1656, CG17575, and CG9997) appear to modulate the long-term response,
      which is the maintenance of post-mating behavior and physiological changes. The
      long-term post-mating response requires presence of sperm in storage and, until
      now, had been known to require only a single Acp. Here, we discovered several
      novel Acps together are required which together are required for sustained egg
      production, reduction in receptivity to remating of the mated female and for
      promotion of stored sperm release from the seminal receptacle. Our results also
      show that members of conserved protein classes found in seminal plasma from
      insects to mammals are essential for important reproductive processes.

PMID- 18085836
TI  - Caution: maintain anti-platelet therapy in patients with coronary artery stents.

PMID- 18085837
TI  - Anesthetic efficacy of buccal and lingual infiltrations of lidocaine following an
      inferior alveolar nerve block in mandibular posterior teeth.
AB  - The authors, using a crossover design, randomly administered, in a single-blind
      manner, 3 sets of injections: an inferior alveolar nerve block (IANB) plus a mock
      buccal and a mock lingual infiltration of the mandibular first molar, an IANB
      plus a buccal infiltration and a mock lingual infiltration of the mandibular
      first molar, and an IANB plus a mock buccal infiltration and a lingual
      infiltration of the mandibular first molar in 3 separate appointments spaced at
      least 1 week apart. An electric pulp tester was used to test for anesthesia of
      the premolars and molars in 3-minute cycles for 60 minutes. Anesthesia was
      considered successful when 2 consecutive 80 readings were obtained within 15
      minutes following completion of the injection sets, and the 80 reading was
      continuously sustained for 60 minutes. For the IANB plus mock buccal infiltration
      and mock lingual infiltration, successful pulpal anesthesia ranged from 53 to 74%
      from the second molar to second premolar. For the IANB plus buccal infiltration
      and mock lingual infiltration, successful pulpal anesthesia ranged from 57 to 69%
      from the second molar to second premolar. For the IANB plus mock buccal
      infiltration and lingual infiltration, successful pulpal anesthesia ranged from
      54 to 76% from the second molar to second premolar. There was no significant
      difference (P > .05) in anesthetic success between the IANB plus buccal or
      lingual infiltrations and the IANB plus mock buccal infiltration and mock lingual
      infiltration. We conclude that adding a buccal or lingual infiltration of 1.8 mL
      of 2% lidocaine with 1:100,000 epinephrine to an IANB did not significantly
      increase anesthetic success in mandibular posterior teeth.

PMID- 18085838
TI  - Five year outcomes study of dental rehabilitation conducted under general
      anesthesia for special needs patients.
AB  - We assessed the safety of general anesthesia for dental treatment of special
      needs patients as it related to American Society of Anesthesiology Physical
      Status (ASAPS) classification, procedure, and other factors. After Institutional
      Review Board review and approval, special needs patients who were admitted to the
      outpatient surgical operating room for comprehensive dental rehabilitation (CDR)
      under general anesthesia within a period of 5 years had their medical records
      evaluated retrospectively for intraoperative and postoperative complications both
      related to anesthesia and surgery. All records were evaluated by an independent
      evaluator who tabulated the patients' age, gender, ASAPS, and duration of
      procedure. N = 363, age mean = 46.93 +/- 16.835 years, age median = 48 years,
      male patients = 180, female patients = 183, ASAPS I =183, ASAPS II = 127, ASAPS
      III = 53, duration of surgery mean = 140.631 +/- 23.104 minutes, duration of
      surgery median time = 142.000 minutes, and number of complications = 2. One
      complication resulted in an ASAPS I 16-year-old boy, which was airway related,
      and a second was an ASAPS III 22-year-old woman, which was surgically related.
      Both led to unplanned inpatient admissions and were treated successfully with no
      residual morbidity. Dental rehabilitation of special needs patients under general
      anesthesia is safe. While morbidity is very low, larger studies are needed to
      establish risk versus benefit stratification among this patient population.

PMID- 18085839
TI  - A case for the lowly case report.

PMID- 18085840
TI  - Cardiovascular drugs: implications for dental practice part 1 - cardiotonics,
      diuretics, and vasodilators.
AB  - Appropriate preoperative assessment of dental patients should always include
      analysis of their medications. Cardiovascular diseases are the most common group
      of medical disorders that dentists encounter, and the number of drugs prescribed
      for managing these conditions is staggering. This justifiably raises concern and
      probable confusion regarding side effects and possible drug interactions with
      medications the dentist may deem necessary for dental care. This continuing
      education article is the first in a series that will address essential
      pharmacology of medications commonly prescribed for chronic medical care. A
      reasonable understanding of these agents will allow the dentist to better
      appreciate the medical status of their patients and avoid adverse interactions
      with drugs they might administer or prescribe.

PMID- 18085843
TI  - Guidelines for psychological practice with girls and women.
AB  - During recent decades, women and girls of diverse ethnicities, social classes,
      sexual orientations, and life experiences have encountered dramatic and complex
      changes in education, health, work, reproductive and caregiving roles, and
      personal relationships. Although many of these changes have resulted in increased
      equality, opportunity, and quality of life, girls and women are also at risk for
      a variety of health concerns and life stresses. The aim of this document is to
      articulate guidelines that will enhance gender- and culture-sensitive
      psychological practice with women and girls from all social classes, ethnic and
      racial groups, sexual orientations, and ability/disability statuses in the United
      States. These guidelines provide general recommendations for psychologists who
      seek to increase their awareness, knowledge, and skills in psychological practice
      with women and girls. The beneficiaries include all consumers of psychological
      practice, including clients, students, supervisees, research participants,
      consultees, and other health professionals. Although the guidelines and
      supporting literature place substantial emphasis on psychotherapy practice, the
      general guidelines are applicable to psychological practice in its broadest
      sense. Rather than offering a comprehensive review of content relevant to all
      areas of practice, this document provides examples of empirical and conceptual
      literature that support the need for practice guidelines.

PMID- 18085844
TI  - Guidelines for education and training at the doctoral and postdoctoral levels in
      consulting psychology/organizational consulting psychology.
AB  - The purpose of these "Guidelines for Education and Training at the Doctoral and
      Postdoctoral Levels in Consulting Psychology/Organizational Consulting
      Psychology" is to provide a common framework for use in the development,
      evaluation, and review of education and training in consulting
      psychology/organizational consulting psychology (CP/OCP). The intent of these
      guidelines is to improve the quality of teaching and learning in the area of the
      practice of CP, especially OCP, within the scientific discipline and profession
      of psychology. Towards these ends, this document is intended as guidance for
      psychologists who teach or plan curricula for teaching CP/OCP at doctoral or
      postdoctoral levels of professional education and training in psychology. The
      guidelines are structured in the form of overarching principles, general
      competencies, and domain-specific competencies that are ideally obtained by
      persons receiving training at the doctoral or postdoctoral level in CP/OCP.

PMID- 18085845
TI  - Record keeping guidelines.
AB  - These guidelines are designed to educate psychologists and provide a framework
      for making decisions regarding professional record keeping. State and federal
      laws, as well as the American Psychological Association's "Ethical Principles of
      Psychologists and Code of Conduct," generally require maintenance of appropriate
      records of psychological services. The nature and extent of the record will vary
      depending upon the purpose, setting, and context of the psychological services.
      Within these guidelines, more directive language has been used when a particular
      guideline is based specifically on mandatory provisions of the Ethics Code or
      law. However, some areas are not addressed in those enforceable standards and
      regulations. In these areas, more aspirational language has been used. This
      document aims to elaborate and provide assistance to psychologists as they
      attempt to establish their own record keeping policies and procedures.

PMID- 18085846
TI  - Corporate funding and conflicts of interest: a primer for psychologists.
AB  - A presidential task force on external funding was established by the American
      Psychological Association (APA) in 2003 to review APA policies, procedures, and
      practices regarding the acceptance of funding and support from private
      corporations for educational and training programs; continuing education
      offerings; research projects; publications; advertising; scientific and
      professional meetings and conferences; and consulting, practice, and advocacy
      relationships. This article, based on the Executive Summary of the APA Task Force
      on External Funding Final Report, presents the findings and unanimous
      recommendations of the task force in the areas of association income, annual
      convention, research and journals, continuing education, education, practice, and
      conflicts of interest and ethics. The task force concluded that it is important
      for both APA and individual psychologists to become familiar with the challenges
      that corporate funding can pose to their integrity. The nature and extent of
      those challenges led the task force to recommend that APA develop explicit
      policies, educational materials, and continuing education programs to preserve
      the independence of psychological science, practice, and education.

PMID- 18085856
TI  - Traits and trade-offs are insufficient for evolutionary personality psychology.
AB  - Comments on the article by D. Nettle, who has clearly shown that evolutionary
      psychologists need to focus more attention on individual differences, not just
      species-typical universals. Such differences are not mere "noise," and
      evolutionary theory will gain by understanding how they are produced and
      maintained. However, by focusing on personality traits and the five-factor
      personality model, Nettle left unaddressed many of the most important aspects of
      human personality. An evolutionary psychology of personality must ultimately
      explain not just trait differences but also differences in personal goals,
      values, motives, identities, and life narratives--essential elements of human
      individuality and functionality. K. M. Sheldon et al suggest four reasons why
      traits and the five-factor personality model do not provide an optimal approach
      for explaining the evolution of personality: (a) As constructs, traits provide
      little purchase for explaining the causes of behavior; (b) trait concepts do not
      acknowledge or explain people's variations around their own baselines, variations
      that are likely crucial for adaptation; (c) traits do not explain or even
      describe true human uniqueness, i.e. the ways in which a person is different from
      everybody else; and (d) traits do not explain personality from the inside, by
      considering what people are trying to do in their lives. In raising these issues
      Sheldon et al are suggesting that the important question for evolutionary
      personality study is not why people fall at different points on a continuum
      regarding traits x, y, and z, but rather why each person is inevitably unique
      while still sharing the same evolved psychology.

PMID- 18085857
TI  - Traits and trade-offs are an important tier.
AB  - Replies to comments by K. M. Sheldon et al on the author's original article on
      evolution and personality variation. Sheldon et al concurred with the thrust of
      that article that the way natural selection shapes or gives rise to
      interindividual variation is a worthy topic for evolutionary psychologists to
      consider, so at a broad level Sheldon et al and Nettle are in agreement. The
      contention concerns the utility of broad traits such as the Big Five personality
      factors in undertaking evolutionary personality psychology. Nettle does not
      concur that traits do not provide a good approach to understanding
      interindividual variation. They have proved their utility in humans and in other
      species. Nettle does agree that traits alone are not sufficient for understanding
      personality functioning, particularly in humans, and hopes that other
      psychologists, including perhaps Sheldon et al, will add an evolution-informed
      understanding of those higher tiers of personality to the framework Nettle has
      suggested for the base tier.

PMID- 18085858
TI  - Ideology as instrument.
AB  - Comments on the article by J. T. Jost, which argued that the end-of-ideology
      claims that emerged in the aftermath of World War II were both incorrect and
      detrimental to the field of political psychology. M. Glassman and D. Karno make
      three critical points. First, Jost objectified ideology as a grand strategy
      implemented at the individual level, rather than as an instrument used for a
      specific purpose in activity. In doing so, he set ideology up as an "object" that
      guides human behavior rather than as a rational part of human experience. Second,
      they take issue with the idea that, because somebody acts in a manner that can be
      categorized as ideological, there actually is such a thing as ideology separate
      from that event and/or political experience and that psychologists ought to
      understand the meaning of ideology in order to understand future human activities
      as outside observers. Third, Jost seems to see this objective ideology as a
      unidirectional, causal mechanism for activity, a mechanism that assumes
      individuals act according to ideology, which eclipses the possibility that
      immediate ideological positions are the residue of purposeful activity. Glassman
      and Karno suggest that it may be better to take a pluralistic view of ideology in
      human action. Where ideology does exist, it is as a purposeful instrument--part
      of a logically based action to meet some ends-in-view--a mixture of immediate
      goals tied to secondary belief systems (which have been integrated to serve the
      material purposes of the purveyors of these ideologies). So if we are to
      understand ideology, we can only understand it through its use in human activity.

PMID- 18085859
TI  - Religious ideology, a neglected variable.
AB  - Comments on an article by J. T. Jost, which presented interesting data relating
      some personality dimensions to voting patterns in the last three U.S.
      presidential elections. R. K. Unger is surprised that in his extensive review of
      the role of ideology, Jost ignored the role of religious ideology in political
      attitudes and voting behavior. There is ample evidence that level of religious
      observance (sometimes labeled religiosity, hierarchical religious beliefs, or
      religious fundamentalism) played a role in 2004 and earlier presidential
      elections. The relationship between religious ideology and political attitudes is
      correlational, and one needs to look further for an explanation of their impact.
      A number of studies indicate relationships between religious fundamentalism and
      what Jost has termed "system-justifying ideologies." Unger suggests that
      religiosity has been largely ignored by psychologists interested in social and
      political behaviors. It is quite possible that religiosity is related to the
      various personality dimensions discussed by Jost. But we cannot learn more about
      these potential connections if we continue to ignore the importance of religious
      ideology as a psychological variable.

PMID- 18085860
TI  - Coda--after "The end of the end of ideology".
AB  - Replies to comments by M. Glassman and D. Karno and R. K. Unger, on the author's
      original article on ideology. J. T. Jost thanks Glassman and Karno for returning
      him to his philosophical roots. Glassman and Karno argued in favor of an
      "instrumental pragmatist" approach to the study of ideology that emphasizes the
      strategic, purposive, goal-directed nature of political rhetoric and belief. He
      agrees that such an approach is helpful and empirically sound. He also agrees
      that ideological movements are often orchestrated by elites (e.g., party leaders)
      for strategic political purposes in a top-down manner. There are several other
      points, however, on which Glassman and Karno seem to misunderstand him. Regarding
      Unger's comments, Unger pointed out, quite correctly, that Jost said relatively
      little about the role of religious ideology in his discussion of ideological
      polarization in the United States. The ideological gulf between religious
      traditionalists and secular humanists has indeed been widening since 1980, and it
      corresponds strongly to right-left differences in political attitudes. Jost
      mentioned, somewhat cryptically, at the end of his article that "similarly
      fruitful analyses could be undertaken with respect to religious and other belief
      systems," and he is grateful for Unger's invitation to elaborate on this point.

PMID- 18085861
TI  - Building more solid bridges between Buddhism and Western psychology.
AB  - Introducing the ways of cultivating mental balance, B. A. Wallace and S. L.
      Shapiro attempted to build bridges between Buddhism and psychology. Their
      systematic categorization of Buddhist teachings and extensive review of empirical
      support from Western psychology are valuable for future study. However, it
      remains a matter of concern that some more profound parts of Buddhist philosophy
      can be disregarded by focusing only on practical aspects of Buddhism within the
      context of mental health. In this comment, the authors briefly address four
      substantial themes to be considered: reality, identity, causality, and
      logicality. They suggest that the way to interpret Buddhism as techniques for
      well-being would certainly be viable in encouraging the study of Buddhist
      teachings in psychology. Yet, such attempts should not result in superficial
      imports and applications of Buddhist practices but give due weight to the deeper
      philosophical issues to build more solid bridges between Buddhism and psychology.

PMID- 18085862
TI  - Speaking of fairness in testing.
AB  - In an article based on her presentation to the 114th Annual Convention of the
      American Psychological Association, Janet Helms described a concept of test
      fairness. Helms's approach to fairness appears to be based on the premise that
      socialization consists of experiences received from one's environment, which are
      simply internalized as personal attributes. From an ecological perspective, this
      is incorrect, misleading, and oddly evocative of social-cognitive and
      psychodynamic notions. Individuals are not passive recipients of culture, and
      they do not necessarily simply reflect their experiences. Although Helms intended
      her model to apply to racial and cultural groups, it seems that she has
      overlooked the potential of applying her concept of fairness to another important
      level of social organization: the family. R. J. Griffore suggests that it is
      unfair to avoid using valid tests that are said to be unfair because of racially
      or culturally based construct-irrelevant variance if those tests can help
      individuals make decisions that lead to success outcomes. The use of race or
      culture as a variable that in any way jeopardizes the prediction of success for
      individuals or groups is unfair for all groups for whom the test is used.

PMID- 18085863
TI  - Racial groups and test fairness, considering history and construct validity.
AB  - According to Helms, "test fairness" is defined as "removal from test scores of
      systematic variance attributable to experiences of racial or cultural
      socialization." Some of Helms's reasoning is based on earlier work, which
      recommended that racial group or category variables be replaced entirely with
      individual-level constructs, to reflect racial socialization experiences that
      vary within racial groups. Treatment of the test fairness issue--a social and
      political issue--will benefit from explicitly considering historical events that
      contributed to group-level race differences. In light of this history, D. A.
      Newman et al suggest (a) retaining a group-level conceptualization of race/racial
      socialization and also (b) focusing on criterion-irrelevant variance in test
      scores that is attributable to race.

PMID- 18085864
TI  - Implementing fairness in racial-group assessment requires assessment of
      individuals.
AB  - Replies to comments by R. J. Griffore and D. A. Newman et al on the author's
      original article on test validity and cultural bias in racial-group assessment.
      Helms notes that, given that within-group variance exceeds between-groups
      variance, racial groups are probably simulating a psychological construct that is
      more strongly related to individuals' test scores than to their respective racial
      group's mean test scores. Therefore, models of individual differences, such as
      her Helms individual-differences (HID) model, that remove construct-irrelevant
      racial variance, are needed to make the testing process fair at the level of
      individual African American, Latino/Latina American, and Native American test
      takers. Her HID model is intended to focus attention on identifying the factors
      responsible for the racial-group-level differences and, thereby, assist test
      users to look beyond presumed physical appearance (e.g., racial-group
      designations) for explanations of individuals' cognitive abilities, knowledge, or
      skills test scores.

PMID- 18085865
TI  - C. M. Louttit and psychological abstracts.
AB  - R. A. Littman indicates that L. T. Benjamin and G. R. VandenBos's history of
      Psychological Abstracts is a fine account of how the American Psychological
      Association has carried out its responsibility to provide access to psychological
      research and writing. Littman was pleased to see Mac Louttit's work as editor
      brought out, and he takes this occasion to give a bit more information about this
      gifted man's career.

PMID- 18085867
TI  - Human and chimpanzee face recognition in chimpanzees (Pan troglodytes): role of
      exposure and impact on categorical perception.
AB  - The respective influences of exposure and inborn neural networks on conspecific
      and nonconspecific face processing remain unclear. Although the importance of
      exposure in the development of object and face recognition in general is well
      documented, studies explicitly comparing face recognition across species showed a
      species-specific effect. For instance, laboratory monkeys exposed daily to human
      faces were better at discriminating monkeys than humans, suggesting that the role
      of exposure may not be the only factor affecting cross-species recognition. In
      the present study, the authors investigated conspecific and nonconspecific face
      recognition in chimpanzees (Pan troglodytes) from 2 primate centers that provided
      different exposure to chimpanzee and human faces. The authors showed that the
      chimpanzees from the center providing more exposure to human faces than to
      chimpanzee faces were better at discriminating human faces than they were at
      discriminating chimpanzee faces. The chimpanzees from the other center did not
      show the same effect. A computational simulation was developed to evaluate the
      average similarities among human pictures and among chimpanzee pictures. Both
      categories were comparable. Chimpanzees' scores were significantly correlated
      with the similarity coefficients. Overall, the results show that exposure is a
      critical determinant in conspecific and nonconspecific face recognition.

PMID- 18085868
TI  - Neural response to emotional pictures is unaffected by concurrent task
      difficulty: an event-related potential study.
AB  - The late positive potential (LPP) is an event-related potential that is enhanced
      when viewing arousing (pleasant and unpleasant) pictures compared to neutral
      pictures. The affective modulation of the LPP is believed to reflect the
      increased attention to, and perceptual processing of, emotional stimuli. The
      present study examined whether concurrent task difficulty (performing
      mathematics) would modulate the LPP while participants viewed emotionally
      arousing stimuli. Results indicated that the LPP was larger following pleasant
      and unpleasant stimuli than it was following neutral stimuli; moreover, the
      magnitude of this increase was not influenced by concurrent task difficulty. This
      finding suggests that the affective modulation of neural activity during picture
      viewing is relatively automatic and is insusceptible to competing task demands.
      Results are further discussed in terms of the LPP's role in motivated attention
      and implications for research on emotion regulation.

PMID- 18085869
TI  - HIV infection affects parietal-dependent spatial cognition: evidence from mental
      rotation and hierarchical pattern perception.
AB  - Human immunodeficiency virus (HIV) in the asymptomatic phase of the infection
      impairs some aspects of cognition, but little is known about how visuospatial
      functions are affected. In the present study, performance on tasks of mental
      rotation and hierarchical pattern perception was investigated in 14 HIV-positive
      men and 12 age- and education-matched HIV-negative men. Processes related to
      mental rotation of objects and hands were impaired in HIV-positive participants
      as compared to the HIV-negative group. The HIV-positive group was also impaired
      on hierarchical pattern perception of local targets under global biasing
      conditions. Consistent with these results, the HIV-positive participants showed
      impaired performance on standard clinical neuropsychological tests of
      visuospatial function. These findings indicate that the detrimental effects of
      HIV on cognition appear even in asymptomatic individuals and affect diverse
      visuospatial functions that depend upon the integrity of parietal brain regions.

PMID- 18085871
TI  - The influence of volition on breathing-swallowing coordination in healthy adults.
AB  - This research was designed to clarify the role of cortical modulation in the
      coordination of respiration and swallowing. Time-locked recordings of submental
      surface electromyography, nasal airflow, and thyroid acoustics were used to
      evaluate nonnutritive breathing-swallowing coordination (BSC) and swallowing
      apnea duration (SAD) of 20 healthy adults during 3 conditions. These conditions
      represented a continuum of volitional through nonvolitional swallowing control on
      the basis of a decreasing level of cortical activation: voluntarily initiated
      swallows during wakefulness, nonvolitional awake swallows, and reflexively
      initiated swallows during sleep. Differing proportions of swallows at the cusps
      between inspiration and expiration were found between the volitional and
      nonvolitional conditions, irrespective of the level of arousal. SAD was unaltered
      by condition. In conclusion, BSC is influenced by degree of volition but not by
      level of arousal. This implies that cortical influence on BSC is limited to
      conditions in which swallowing is voluntarily initiated and indirectly implicates
      the recruitment of the supplementary motor or insular cortices. SAD remained
      stable across conditions and may therefore be considered relatively impervious to
      suprabulbar influence.

PMID- 18085872
TI  - The "Swedish" mutation of the amyloid precursor protein (APPswe) dissociates
      components of object-location memory in aged Tg2576 mice.
AB  - Aged Tg2576 mice show abnormalities in hippocampal morphology and physiology and
      display behavioral deficits in spatial navigation tasks consonant with a deficit
      in the functional properties of the hippocampus. However, the nature of the
      spatial representations disrupted by the "Swedish" mutation of the amyloid
      precursor protein (APPswe) is unclear. In an effort to characterize the memory
      deficits in Tg2576 mice, the spontaneous object exploration paradigm was used to
      interrogate spatial and object memory in mice. With object arrays of comparable
      size, 16-month-old Tg2576 mice showed a normal object familiarity/novelty effect
      but impaired memory for the location of objects when 2 objects exchanged
      locations (topological transformation; Experiment 1). In contrast, Tg2576 mice
      showed preferential exploration of familiar objects when they were moved to
      previously unoccupied locations (Experiment 2), irrespective of whether the
      transformation altered the metric properties of the object array (Experiments 3).
      These results suggest that Tg2576 mice are able to form representations of the
      identity of objects and a memory of the spatial organization of objects in an
      arena. In contrast, conjunctive memory for specific object-location associations
      is severely impaired in aged Tg2576 mice.

PMID- 18085873
TI  - Targeted deletion of the GluR-1 AMPA receptor in mice dissociates general and
      outcome-specific influences of appetitive rewards on learning.
AB  - The authors assessed the hypothesis that deletion of the GluR-1 subtype of the
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor in mice
      disrupts the associative activation of a sensory-specific representation of an
      appetitive reward. In Experiment 1, mice received training on a Pavlovian
      instrumental transfer task. In the test stage, conditioned stimulus (CS)
      presentations enhanced instrumental actions in both groups. However, this effect
      was specific to the action that shared the same outcome as the CS in wild-type
      (WT), but not GluR-1-super(-/-), mice. In Experiment 2, the mice were trained on
      a heterogeneous instrumental chain in which rewards were obtained for emitting 1
      response (R1, that was distal to reward delivery), followed by a 2nd response
      (R2, that was proximal to reward delivery). A change in general motivational
      state (from hungry to sated) reduced the number of R2 responses in both groups.
      In contrast, an outcome-specific satiety treatment produced a selective decline
      in R1 responding only in WT mice. The results support the hypothesis that GluR-1
      deletion impairs the associative activation of a representation of the sensory
      specific incentive motivational properties of an appetitive reward.

PMID- 18085874
TI  - The cognitive enhancer T-588 partially compensates the motor associative learning
      impairments induced by scopolamine injection in mice.
AB  - The authors studied the effects of T-588 on scopolamine-induced memory
      impairments in the acquisition of a classical eyeblink conditioning in behaving
      adult mice. Mice injected with 0.3 mg/kg of scopolamine showed a marked deficit,
      compared with nontreated mice, in the acquisition of classical eyeblink
      conditioning using a trace paradigm. Coadministration of T-588 (0.05% wt/vol, in
      water) with scopolamine (0.3 mg/kg) significantly prevented this deficit in
      associative learning. To further assess the effects of T-588 on motor
      coordination and the cognitive deficits induced by scopolamine, the authors
      compared adult controls or scopolamine-treated mice in different behavioral
      tasks: rotarod, object recognition, passive avoidance, and prepulse inhibition.
      In all of these tasks, the authors found a significant impairment in the motor or
      cognitive abilities in scopolamine-injected mice, compared with controls. In
      addition, the coadministration of T-588 with scopolamine restored deficits
      induced by scopolamine alone. Importantly, the administration of T-588 alone did
      not evoke any change compared with values obtained for controls. These results
      suggest that T-588 could be used as a pharmacological agent to improve motor and
      associative learning disorders.

PMID- 18085875
TI  - Muscarinic receptor antagonism of the nucleus accumbens core causes avoidance to
      flavor and spatial cues.
AB  - Pharmacological blockade of muscarinic receptors in the nucleus accumbens reduces
      food intake and instrumental behaviors that are reinforced by food delivery.
      Nucleus accumbens muscarinic antagonism may specifically suppress the hedonic or
      reinforcing effects of food, thus blocking its capacity to direct behavior.
      Alternatively, muscarinic receptor blockade may cause a negative hedonic state
      that interferes with appetitive learning and food intake. In these experiments,
      rats received infusions of scopolamine methyl bromide (10 microg/0.5 microl) into
      the nucleus accumbens core, following exposure to a novel flavor of liquid diet
      (Experiment 1) or prior to being placed into a place preference apparatus
      (Experiment 2). In both experiments, nucleus accumbens muscarinic receptor
      antagonism caused subsequent avoidance of the paired cue (flavor or spatial
      location). This effect was specific to cholinergic manipulation; no conditioned
      taste avoidance was observed after pairing the novel flavor with nucleus
      accumbens core antagonism of N-methyl-D-aspartate, dopamine D-sub-1, or opioid
      receptors (Experiment 3). These experiments confirm previous reports of a
      critical role for striatal acetylcholine in modulating goal-directed behaviors,
      but suggest caution when interpreting behavioral effects of pharmacological
      manipulation of striatal acetylcholine.

PMID- 18085876
TI  - Selective ablation of GABA neurons in the ventral tegmental area increases
      spontaneous locomotor activity.
AB  - Gamma-aminobutyric acid (GABA) neurons in the ventral tegmental area (VTA)
      provide innervation to cortical and subcortical regions of the brain. To solidify
      the importance of these VTA GABA neurons in behavioral function, we employed the
      neurotoxin dermorphin-saporin (DS) to selectively lesion VTA GABA neurons prior
      to assessing spontaneous motor activity. Rats were bilaterally microinfused with
      DS (1.0 or 2.0 pmol/200 nl/side) or blank-saporin control (BS, 200 nl/side) into
      the VTA. Seven days later, DS-treated rats exhibited significantly elevated
      motility in comparison with BS-treated rats; this elevated motility normalized by
      Day 14 following pretreatment with 1.0 pmol of DS but was sustained on Day 14
      after pretreatment with 2.0 pmol of DS. A selective loss of VTA GABA neurons on
      Day 14 was demonstrated through reduced expression of mRNA for glutamic acid
      decarboxylase-67 and micro-opioid receptor, but not tyrosine hydroxylase (a
      dopamine neuron marker), in the VTA. Thus, a dose- and time-related selective
      loss of VTA GABA neurons was accomplished using this novel neurotoxin. This loss
      of GABA VTA neurons was associated with hypermotility, further supporting their
      important regulatory role in the generation of behavior.

PMID- 18085877
TI  - Once is too much: conditioned changes in accumbens dopamine following a single
      saccharin-morphine pairing.
AB  - The present study tested whether presentation of a taste cue would support
      conditioned suppression of dopamine in the nucleus accumbens (NAcc) following a
      single taste-drug pairing. Nondeprived male Sprague-Dawley rats were given 20-min
      access to a 0.15% saccharin conditioned stimulus (CS). Immediately thereafter,
      experimental rats were injected with morphine (15 mg/kg ip); standard controls
      were injected with saline; and explicitly unpaired controls were injected with
      morphine, but approximately 24 hr later. All rats were then given one 20-min CS
      only test. Microdialysis samples from the NAcc were measured over 20-min
      intervals before, during, and after CS access on the conditioning and test trial.
      The results showed that a single saccharin-morphine pairing led to a marked
      reduction in CS intake, and the reduction in intake was accompanied by a
      conditioned blunting of the accumbens dopamine response to the saccharin reward
      cue. In turn, a single exposure to the saccharin cue also blunted the
      unconditioned dopamine response to morphine. Reward comparison effects, then, are
      cross-modal, bidirectional, and immediate, resulting in both unconditioned and
      conditioned changes in brain and behavior.

PMID- 18085878
TI  - Contextual modulation of conditioned responses: role of the ventral subiculum and
      nucleus accumbens.
AB  - The performance of conditioned responses (CRs) is diminished when trained
      subjects are tested in a novel context. This study tested the hypothesis that the
      flow of contextual information along the disynaptic "ESA" (entorhinal cortex
      ventral subiculum-nucleus accumbens) pathway is responsible for context-related
      modulation of CRs. Rabbits received electrolytic or sham lesions of the ventral
      subiculum followed by discriminative avoidance conditioning and counterbalanced
      extinction sessions in the original training context, a novel context, and the
      original training context with a novel cue. Neuronal activity was recorded
      simultaneously in the nucleus accumbens, cingulate cortex, and basolateral
      amygdala. The lesions did not affect the acquisition of avoidance behavior or
      prevent the reduction of CRs in response to a novel cue. However, the lesions did
      reduce CR incidence during extinction, and they did eliminate a further novel
      context-induced CR reduction found in controls. In addition, lesions disrupted
      context-dependent neuronal responses in the nucleus accumbens but not in the
      cingulate cortex or amygdala. These findings are interpreted as supportive of the
      hypothesis that the ESA pathway mediates contextual modulation of CRs during
      extinction.

PMID- 18085879
TI  - Impaired processing of local geometric features during navigation in a water maze
      following hippocampal lesions in rats.
AB  - Hippocampal damage impairs navigation with respect to information provided by the
      shape of an arena. Recent evidence has suggested that normal rats use local
      geometric information, as opposed to a global geometric representation, to
      navigate to a correct corner. One implication of this pattern of results is that
      hippocampal lesions may impair processing of 1 or more of the local geometric
      features of an environment. The authors therefore investigated the effects of
      hippocampal cell loss in rats on navigation to a hidden goal with respect to a
      variety of local cues in an environment with a distinctive shape. Rats with
      lesions of the hippocampus were impaired in discriminating a right-angled corner
      from its mirror image. However, they were able to use cues provided by an acute
      angled corner (Experiment 1) or a local polarizing cue (Experiment 2). In
      contrast, lesioned rats were impaired in discriminating long versus short walls
      (Experiment 3). Results indicate that the hippocampus plays a role in
      disambiguating locations by processing (metric) information related to the
      distance between corners.

PMID- 18085880
TI  - Oral methylphenidate improves spatial learning and memory in pre- and
      periadolescent rats.
AB  - Methylphenidate (MPD) is widely prescribed for attention-deficit/hyperactivity
      disorder in the United States. Patients, mostly school-age children, are taking
      the drug orally. To simulate the human condition, the authors used a cracker to
      administer methylphenidate orally (without the stress of handling) from Postnatal
      Day (PND) 22 to PND 40 and determined the effects of daily low-dose
      administration on the learning and performance of a radial arm maze win-shift
      task with all 8 arms baited. Number of entries to repeat, time to finish 8
      entries, and days to reach criterion (at least 7 entries without errors for 4 out
      of 5 consecutive trials) were evaluated. An improvement during the first 7 days
      was revealed in both male and female rats treated with 3.0 mg/kg of oral
      methylphenidate compared with the controls. On PND 40, locomotor activity levels
      were not significantly different in the 3.0 mg/kg treated group compared with the
      controls during the initial 5 min or during the full 1 hr of recording. These
      data suggest that oral administration of low-dose MPD improves spatial learning
      and memory in both male and female preadolescent rats.

PMID- 18085881
TI  - Effects of ethanol on encoding, consolidation, and expression of extinction
      following contextual fear conditioning.
AB  - Studies of contextual fear conditioning have found that ethanol administered
      prior to a conditioning session impairs the conditioned freezing response during
      a test session the next day. The present experiments examined the effects of
      ethanol on extinction, the loss of conditioned responding that occurs as the
      animal learns that a previously conditioned context no longer signals shock.
      Ethanol (1.5 g/kg) administered prior to single (Experiment 1) or multiple
      (Experiment 2) extinction sessions impaired extinction. Ethanol administered
      prior to a test session disrupted the expression of freezing after extinction
      (Experiments 3-5). There was some evidence that ethanol served as an internal
      stimulus signaling the operation of conditioning or extinction contingencies
      (Experiments 4-5). In Experiment 6, postsession injections of 1.5 g/kg ethanol
      had no effect on extinction with brief (3 min) or long (24 min) exposures to the
      context, but injections of 3 g/kg after long exposures impaired extinction.
      Together, these results indicate that ethanol affects extinction by acting on
      multiple learning and performance processes, including attention, memory
      encoding, and memory expression.

PMID- 18085882
TI  - Experience-induced fetal plasticity: the effect of gestational ethanol exposure
      on the behavioral and neurophysiologic olfactory response to ethanol odor in
      early postnatal and adult rats.
AB  - Human fetal ethanol exposure is strongly associated with ethanol avidity during
      adolescence. Evidence that intrauterine olfactory experience influences
      chemosensory-guided postnatal behaviors suggests that an altered response to
      ethanol odor resulting from fetal exposure may contribute to later abuse risk.
      Using behavioral and neurophysiological methods, the authors tested whether
      ethanol exposure via the dam's diet resulted in an altered responsiveness to
      ethanol odor in infant and adult rats. Compared with controls, (a) fetal exposure
      tuned the neurophysiologic response of the olfactory epithelium to ethanol odor
      at some expense to its responsiveness to other odorants in infantile rats--this
      effect was absent in adults; (b) the neural effect in infantile rats was
      paralleled by an altered behavioral response to ethanol odor that was specific to
      this odorant--this effect was also absent in adults; and (c) a significant
      component of the infantile behavioral effect was attributable to ethanol's effect
      on the olfactory neural modality. These data provide evidence for an important
      relationship between prenatal ethanol experience and postnatal behavioral
      responsiveness to the drug that is modulated or determined by olfactory function.

PMID- 18085883
TI  - The effect of gestational ethanol exposure on voluntary ethanol intake in early
      postnatal and adult rats.
AB  - Clinical and epidemiological studies provide strong data for a relationship
      between prenatal ethanol exposure and the risk for abuse in adolescent and young
      adult humans. However, drug-acceptance results in response to fetal exposure have
      differed by study, age at evaluation, and experimental animal. In the present
      study, the authors tested whether voluntary ethanol intake was enhanced in both
      the infantile and adult rat (15 and 90 days of age, respectively), as a
      consequence of chronic fetal drug experience. Experimental rats were exposed in
      utero by administering ethanol to a pregnant dam in a liquid diet during
      gestational Days 6-20. Compared with those for isocaloric pair-fed and ad lib
      chow control animals, the results for experimental animals demonstrated that
      fetal exposure significantly increased infantile affinity for ethanol ingestion
      without affecting intake patterns of an alternative fluid (water). Heightened
      affinity for ethanol was absent in adulthood. Moreover, the results argue against
      malnutrition as a principal factor underlying the infantile phenomenon. These
      data add to a growing literature indicative of heightened early postnatal
      acceptance patterns resulting from maternal use or abuse of ethanol during
      pregnancy.

PMID- 18085885
TI  - Immediate post-reminder injection of gamma-amino butyric acid (GABA) agonist
      midazolam attenuates reactivation of forgotten fear in the infant rat.
AB  - J. H. Kim, G. McNally, and R. Richardson (2006) reported that pretest injection
      of FG7142, a GABA inverse agonist, alleviated infantile amnesia in rats. From
      this, it was concluded that GABAergic neurotransmission is involved in the
      forgetting seen in the developing rat. The present study extends that finding by
      examining the role of GABA in the reactivation of a forgotten memory in the
      infant rat. Sixteen-day-old rats were conditioned to fear a white noise. When
      tested 3 days later, rats that had not received a reminder treatment exhibited
      substantial forgetting. Reactivation of memory (as assessed by high levels of
      freezing) was observed in rats that were given a reminder shock and injected with
      saline the day before test. However, rats given a reminder shock and injected
      with midazolam immediately afterward failed to exhibit the reactivation effect. A
      subsequent experiment replicated this finding and further showed that midazolam
      did not reduce the memory reactivation effect when injected 2 hr after the
      reminder episode. From this, it appears that alterations in GABAergic
      neurotransmission may be an underlying process mediating memory reactivation in
      the infant rat.

PMID- 18085884
TI  - Neonatal amygdala lesions: co-occurring impact on social/fear-related behavior
      and cocaine sensitization in adult rats.
AB  - Neurodevelopmental abnormalities of temporal-limbic structures may underlie both
      adult psychiatric syndromes and increased addiction vulnerability, leading to
      high frequencies of "dual diagnosis" disorders. Although the amygdala is
      implicated in various mental disorders and drug addiction, no studies have
      explored the impact of early developmental damage to the amygdala on phenotypes
      relating to mental illness and addictions as co-occurring processes. We tested
      rats with neonatal amygdala lesions (NAML) vs. SHAM-operated controls in a
      battery of tests--novel field activity, elevated plus maze (EPM), and social
      interaction (SI) at baseline and after odor and restraint stress--followed by
      measures of cocaine sensitization (15 mg/kg vs. saline x 5 days + challenge
      session 2 weeks later) and remeasurement of SI. NAMLs showed increased novelty
      related locomotion, less fear responding in the EPM, and resistance to predator
      odor- but not to restraint-induced suppression of SI. NAMLs also had elevated
      cocaine sensitization profiles, and cocaine history differentially affected
      subsequent SI in NAMLs compared with SHAMs. NAMLs may provide models for
      understanding a shared neurobiological basis for and complex interactions among
      psychiatric symptoms, drug exposure history, and addiction vulnerability.

PMID- 18085886
TI  - Rat behavioral thermoregulation integrates with nonshivering thermogenesis during
      postnatal development.
AB  - Rat pups are capable of behavioral thermoregulation, both in the nest and on a
      thermocline, as early as the 1st week of postnatal life, and these pups can also
      produce heat metabolically without shivering. The rat pup's primary source of
      nonshivering thermogenesis is the sympathetically mediated metabolism of brown
      adipose tissue (BAT). BAT is well formed in newborns and functions shortly after
      birth. While infant behavioral thermoregulation and BAT thermogenesis have been
      extensively studied, little is known about the extent to which thermoregulatory
      behavior can be influenced by BAT thermogenesis. In the present study, 2-, 7-,
      and 14-day-old pups were observed on a thermal gradient following pharmacological
      stimulation or inhibition of BAT thermogenesis, and their thermal preferences
      were quantified. The authors found that 7- and 14-day-old pups treated with
      norepinephrine (NE), which increases BAT thermogenesis, preferred cooler portions
      of the gradient than saline-treated controls, whereas 2-day-olds failed to show a
      similar NE-induced behavioral adjustment. These findings indicate that the
      ability to adjust thermoregulatory behavior to compensate for enhanced metabolic
      thermogenesis develops during the 1st week of postnatal life.

PMID- 18085887
TI  - Chronic neonatal nicotine increases anxiety but does not impair cognition in
      adult rats.
AB  - Developmental nicotine exposure has been implicated in the association between
      maternal smoking and adverse outcomes in offspring. The 3rd trimester of human
      pregnancy is equivalent to the 1st postnatal week in rodents; both are periods of
      active brain growth during which nicotinic acetylcholine receptors are
      transiently upregulated. Chronic neonatal nicotine (CNN; 6 mg/kg/day) from
      postnatal Days 1 to 7 was given orally to rat pups to evaluate long-term
      behavioral effects. Males and females were tested as adolescents or as young
      adults. CNN significantly decreased center time, ambulatory behavior, and rearing
      in the open-field test and decreased the number of entrances and time spent in
      the open arm of the elevated plus-maze in both sexes and ages. CNN did not change
      performance in the T maze or in the water maze in adult males or females. Motor
      coordination was not altered. In summary, CNN had long-term effects on anxiety
      like behavior but did not affect spatial learning and memory functions. This
      finding is particularly important when evaluating the benefits of nicotine
      replacement therapies during human pregnancies, which may improve smoking
      cessation rates but could result in long-term behavioral consequences.

PMID- 18085888
TI  - Transgenerational effects of social environment on variations in maternal care
      and behavioral response to novelty.
AB  - Cross-fostering studies in the rat have illustrated the importance of the
      postnatal environment in mediating the transmission of maternal licking/grooming
      (LG) from mother to offspring. The authors addressed the question of how
      postweaning social conditions can alter the patterns of maternal behavior.
      Juvenile female offspring of high LG and low LG mothers were placed in either
      standard, enriched, or impoverished postweaning environments for 50 consecutive
      days and then mated and observed with their own litters. Analysis of LG behavior
      indicated that the effect of postweaning environment was dependent on the level
      of postnatal mother-infant interaction. Postweaning isolation reduced exploratory
      behavior, maternal LG, and oxytocin receptor binding in the offspring of high LG
      mothers, whereas social enrichment enhanced exploration, LG behavior, and
      oxytocin receptor binding of low LG offspring. These effects were also
      transmitted to the next generation of offspring. Thus, maternal LG and the neural
      mechanisms that regulate this behavior exhibited a high degree of plasticity in
      response to changes in environment both within and beyond the postnatal period,
      with implications for the transmission of behavioral response to novelty and
      maternal care across generations.

PMID- 18085890
TI  - Brain regional neuropeptide changes resulting from social defeat.
AB  - Past work has demonstrated robust brain changes in cholecystokinin (CCK-8)
      following social defeat. Here the authors analyzed brain regional, CCK-8,
      substance P, corticotropin releasing factor (CRF), and neuropeptide Y levels in
      adult male Long-Evans rats defeated in a resident-intruder social aggression
      paradigm, as indexed by elevated bites received, freezing, and emission of 20-kHz
      calls. Brains harvested 6 hr after social defeat were dissected into 12 regions
      (olfactory bulbs, 3 cortical regions [frontal cortex, cortex above the basal
      ganglia, cortex above the diencephalon], caudate-putamen, basal forebrain,
      hypothalamus, hippocampus, thalamus, tectum, tegmentum, and lower brain stem).
      Neuropeptide radioimmunoassays demonstrated the following statistically
      significant regional changes in defeated rats as compared with nondefeated rats:
      CCK-8 was reduced in frontal cortex and cortex overlying diencephalon, the
      olfactory bulbs, caudate-putamen, hippocampus, tectum, and lower brainstem.
      Neuropeptide Y was elevated in the caudate-putamen. Substance P was elevated in
      the cortex over the basal ganglia and decreased in basal forebrain. CRF was
      diminished in the hippocampus. The results highlight more robust CCK modulation
      by social defeat as compared with 3 other neuropeptide systems involved in brain
      emotional regulation.

PMID- 18085891
TI  - Motivated attention and prepulse inhibition of startle in rats: using conditioned
      reinforcers as prepulses.
AB  - In humans, prepulse inhibition (PPI) of startle is greater during attended
      prestimuli than it is during ignored prestimuli, whereas in rats, most work has
      focused on passive PPI, which does not require attention. In the work described
      in this article, researchers developed a paradigm to assess attentional
      modification of PPI in rats using motivationally salient prepulses. Water
      deprived rats were either conditioned to attend to a conditioned stimulus (CS; 1
      s, 7-dB increase in white noise) paired with water (CS(+) group), or they
      received uncorrelated presentations of white noise and water (CS0 group). After
      10 conditioning sessions, startle probes (50 ms, 115 dB) were introduced, with
      the CS serving as a continuous prepulse. Three experiments examined PPI across a
      range of prepulse intensities (4-10 dB) and stimulus onset asynchronies (SOAs; 30
      960 ms). PPI was consistently reduced in the CS(+) group, particularly with a 10
      dB prepulse and a 60-ms SOA. Thus, PPI in rats differed between attended and
      ignored prestimuli, but the effect was reversed in the results of research with
      humans. A fourth study eliminated the group difference by reversing the CS-water
      contingency. Methodological and motivational hypotheses regarding the current
      findings are discussed.

PMID- 18085892
TI  - Importance of retronasal and orthonasal olfaction for odor aversion memory in
      rats.
AB  - The role of odors in food memory formation, especially for aversions, has long
      been considered secondary to taste. However, the importance of odor ingestion in
      conditioned odor aversion (COA) has recently challenged this assumption (B. M.
      Slotnick, F. Westbrook, & F. M. C. Darling, 1997). The aim of the present study
      was to evaluate the respective role of orthonasal and retronasal olfactory
      experience in COA acquisition, long-term retention, extinction, and spontaneous
      recovery. To this end, the odor was presented either close to the drinking spout
      (orthonasal stimulation) or close to and mixed with the drinking water (eliciting
      both orthonasal and retronasal stimulation). The authors brought evidence that
      odor ingestion was crucial for COA acquisition, especially when odor presentation
      and gastric malaise were separated by long delays. On the contrary, once formed,
      a distal (orthonasal) odor recognition was sufficient for COA to be retrieved.
      COA was odor specific and long lasting (more than 50 days). Moreover, results
      brought evidence for a spontaneous recovery of odor aversion tested 57 days after
      its extinction.

PMID- 18085893
TI  - Functional coupling between substantia nigra and basal ganglia homologues in
      amphibians.
AB  - Neuroanatomical and pharmacological experiments support the existence of a
      homologue of the mammalian substantia nigra-basal ganglia circuit in the
      amphibian brain. Demarcation of borders between the striatum and pallidum in
      frogs, however, has been contentious, and direct evidence of functional coupling
      between the putative nigral and striatal homologues is lacking. To clarify basal
      ganglia function in anurans, the authors used expression of immediate-early gene
      egr-1 as a marker of neural activation in the basal ganglia of tungara frogs
      (Physalaemus pustulosus). Regional variation in egr-1 mRNA levels distinguished
      striatal and pallidal portions of the basal ganglia and supported the grouping of
      the striatopallidal transition zone with the dorsal pallidum. As further evidence
      for a functional coupling between the dopaminergic cells in the posterior
      tuberculum (the putative substantia nigra homologue) and the basal ganglia, a
      positive relationship was demonstrated between the size of the dopaminergic cell
      population and the neural activation levels within the dorsal pallidum.

PMID- 18085894
TI  - Impairment of long-term associative memory in aging snails (Lymnaea stagnalis).
AB  - Age-dependent impairment in learning and memory functions occurs in many animal
      species, including humans. Although cell death contributes to age-related
      cognitive impairment in pathological forms of aging, learning and memory
      deficiencies develop with age even without substantial cell death. The molecular
      and cellular basis of this biological aging process is not well understood but
      seems to involve a decline in the aging brain's capacity for experience-dependent
      plasticity. To aid in resolving this issue, we used a simple snail appetitive
      classical conditioning paradigm in which the underlying molecular, cellular, and
      neural network functions can be directly linked to age-associated learning and
      memory performance (i.e., the Lymnaea stagnalis feeding system). Our results
      indicate that age does not affect the acquisition of appetitive memory but that
      retention and/or consolidation of long-term memory become progressively impaired
      with advancing age. The latter phenomenon correlates with declining
      electrophysiological excitability in key neurons controlling the feeding
      behavior. Together, these results present the Lymnaea feeding system as a
      powerful paradigm for investigations of cellular and molecular foundations of
      biological aging in the brain.

PMID- 18085895
TI  - Acute administration of interleukin-1beta disrupts motor learning.
AB  - Proinflammatory cytokines have been shown to disrupt the normal transfer of short
      term memory to long-term storage sites. Previous research has focused
      predominantly on the effect of cytokines on hippocampus-mediated spatial
      learning. To further understand the effects of cytokines on learning and memory,
      the authors evaluated the effects of interleukin-1beta (IL-1beta) on a motor
      learning task. Male Long-Evans rats were rewarded with food pellets after they
      traversed a runway. The runway was either flat (control condition) or had up
      ended dowels (motor learning condition). Subjects traversed the flat runway or
      dowel task for 5 days, 10 trials per day, and were treated with either saline or
      with 4 microg/kg IL-1beta immediately after training on the first 2 days. Rats in
      the motor learning task treated with IL-1beta were consistently slower at
      traversing the runway. IL-1beta did not impair performance in the control
      condition; rats in the flat condition performed similarly regardless of whether
      they were treated with saline or IL-1beta. These data are the first evidence
      demonstrating IL-1beta can disrupt performance in a motor learning task.

PMID- 18085896
TI  - The effects of FG7142 on two types of forgetting in 18-day-old rats.
AB  - The authors studied the role of gamma-aminobutyric acid (GABA) in 2 types of
      forgetting of fear in the developing rat. One type of forgetting studied was that
      observed after an intermediate retention interval (the "Kamin effect"); the other
      type studied was that observed after a longer interval (infantile amnesia). Rats
      were given pairings of an auditory conditioned stimulus with shock, and learned
      fear was assessed by freezing. Forgetting at an intermediate retention interval
      (1 hr) was not alleviated by the GABA-sub(A) receptor partial inverse agonist
      FG7142 (0, 1, 5, or 10 mg/kg), whereas forgetting at a longer retention interval
      (48 hr) was alleviated. These results suggest that in the developing rat,
      forgetting observed at different retention intervals is mediated by different
      physiological mechanisms.

PMID- 18085897
TI  - Preweanling rats solve the Morris water task via directional navigation.
AB  - Adult rats show a preference for directional navigation over place navigation in
      the Morris water task. Here, the authors investigated whether preweanling rats
      with a newly developed ability to perform the water task also solve the task via
      directional navigation. After 24-day-old rats were trained to find a hidden
      platform in a fixed spatial location, a no-platform probe trial was conducted
      with the pool either in the same position as that used during training (no shift
      group) or shifted to a new position in the room (shift group). The authors found
      that rats in the shift group did not search for the platform at its absolute
      spatial location but rather navigated in the same direction that the platform was
      located during training and searched at the correct distance from the pool wall,
      resulting in a search at a location that was never trained. This pattern of
      results suggests that young rats learn to solve the water task by navigating in a
      particular direction rather than navigating to a precise place--a finding that
      may have implications for understanding hippocampal development.

PMID- 18085898
TI  - Role of the medial prefrontal cortex in acquired distinctiveness and equivalence
      of cues.
AB  - In the present study, the authors examined the role of the medial prefrontal
      cortex in acquired equivalence and distinctiveness of cues. Rats were placed in 4
      experimental contexts (A, B, C, and D) where they received presentations of 2
      auditory stimuli (X and Y). In Contexts A and B, X was paired with food and Y was
      not, whereas in Contexts C and D, Y was paired with food and X was not. Rats that
      received sham lesions and those with lesions of the medial prefrontal cortex
      acquired this configural discrimination equally readily. Rats then received many
      pellets in A but not in C. After this training, sham-lesion rats exhibited more
      magazine activity in B than in D (an acquired distinctiveness/acquired
      equivalence effect), whereas those with medial prefrontal cortex lesions did not.
      These results indicate that the medial prefrontal cortex is involved in the
      process by which experience with stimuli influences the degree of generalization
      between them.

PMID- 18085899
TI  - Understanding the developmental origins of primate face recognition: theoretical
      commentary on Martin-Malivel and Okada (2007).
AB  - J. Martin-Malivel and K. Okada (2007, this issue) reported that chimpanzees
      raised with extensive social contact with humans show face discrimination
      abilities for human faces that exceed those for conspecific faces. Martin-Malivel
      and Okada have placed this finding in the theoretical context of the relative
      role of experience and innate face representations. The present article discusses
      the logic of the various styles of studies relevant to this question--considering
      primates without prior visual experience, sensitive periods, perceptual
      narrowing, childhood development, other-species effects, other-race effects,
      social quality of experience with nonconspecifics, and perceived social group
      membership--and also reviews the key current data. A case is made that there is
      still a long way to go in understanding whether there is an innate representation
      of conspecific faces, how tightly tuned any such representation is to conspecific
      morphology, and how experience obtained during different age brackets (e.g.,
      infancy versus adulthood) affects discrimination and interacts with any innate
      representation.

PMID- 18085900
TI  - Does shape matter? Theoretical comment on Jones, Pearce, Davies, Good, and
      McGregor (2007).
AB  - An influential view in the field of spatial cognition is that an obligatory
      geometric module constrains spatial learning and memory. In this issue, P. M.
      Jones, J. M. Pearce, V. J. Davies, M. A. Good, and A. McGregor (2007) showed that
      learning based on the geometry, or shape, of the environment requires the
      hippocampus. To place this work in context, the author of the present article
      considers the evidence for and against a geometric module for rat spatial
      learning, outlines the influence of geometry on neurons that encode spatial
      information, and attempts to relate spatial behavior to neuronal representations
      of direction and location.

PMID- 18085901
TI  - Treatment integrity in psychotherapy research: analysis of the studies and
      examination of the associated factors.
AB  - Treatment integrity refers to the degree to which an intervention is delivered as
      intended. Two studies evaluated the adequacy of treatment integrity procedures
      (including establishing, assessing, evaluating, and reporting integrity;
      therapist treatment adherence; and therapist competence) implemented in
      psychotherapy research, as well as predictors of their implementation. Randomized
      controlled trials of psychosocial interventions published in 6 influential
      psychological and psychiatric journals were reviewed and coded for treatment
      integrity implementation. Results indicate that investigations that
      systematically addressed treatment integrity procedures are virtually absent in
      the literature. Treatment integrity was adequately addressed for only 3.50% of
      the evaluated psychosocial interventions. Journal of publication and treatment
      approach predicted integrity implementation. Skill-building treatments (e.g.,
      cognitive-behavioral) as compared with non-skill-building interventions (e.g.,
      psychodynamic, nondirective counseling) were implemented with higher attention to
      integrity procedures. Guidelines for implementation of treatment integrity
      procedures need to be reevaluated.

PMID- 18085902
TI  - Untangling the alliance-outcome correlation: exploring the relative importance of
      therapist and patient variability in the alliance.
AB  - Although the therapeutic alliance is a consistent predictor of psychotherapy
      outcomes, research has not distinguished between the roles of patient and
      therapist variability in the alliance. Multilevel models were used to explore the
      relative importance of patient and therapist variability in the alliance as they
      relate to outcome among 331 patients seen by 80 therapists (therapist average
      caseload was 4.1). Patients rated both the alliance and outcome and all models
      adjusted for baseline psychological functioning. The results indicated that
      therapist variability in the alliance predicted outcome, whereas patient
      variability in the alliance was unrelated to outcome. Reasons why therapist
      variability as opposed to patient variability predicted outcome are discussed.
      Clinical implications include therapists monitoring their contribution to the
      alliance, clinics providing feedback to therapists about their alliances, and
      therapists receiving training to develop and maintain strong alliances.

PMID- 18085903
TI  - Increasing attendance for psychotherapy: implementation intentions and the self
      regulation of attendance-related negative affect.
AB  - The present study evaluated an implementation intention intervention that aimed
      to increase attendance at scheduled, initial appointments for psychotherapy by
      helping clients to manage negative feelings about attendance. Participants
      received a postal questionnaire that measured their views about attending
      psychotherapy. One half of the sample was randomly assigned to an implementation
      intention induction that was embedded in the questionnaire. Intention-to-treat
      analysis (N=390) indicated that participants who formed implementation intentions
      were more likely to attend compared to controls (75% vs. 63%), and this effect
      was even stronger among participants who returned the questionnaire (83% vs.
      57%). Whereas anticipated affective costs (e.g., shame) had a negative impact on
      attendance for most participants, this effect was attenuated when participants
      formed implementation intentions and perceived that attendance would be
      beneficial. Thus, implementation intention formation can help clients to deal
      effectively with negative feelings that might otherwise prevent them attending
      their first psychotherapy appointment.

PMID- 18085905
TI  - Emotional processing in experiential therapy: why "the only way out is through.".
AB  - The purpose of this study was to examine observable moment-by-moment steps in
      emotional processing as they occurred within productive sessions of experiential
      therapy. Global distress was identified as an unprocessed emotion with high
      arousal and low meaningfulness. The investigation consisted of 2 studies as part
      of a task analysis that examined clients processing distress in live video
      recorded therapy sessions. Clients in both studies were adults in experiential
      therapy for depression and ongoing interpersonal problems. Study 1 was the
      discovery-oriented phase of task analysis, which intensively examined 6 examples
      of global distress. The qualitative findings produced a model showing: global
      distress, fear, shame, and aggressive anger as undifferentiated and
      insufficiently processed emotions; the articulation of needs and negative self
      evaluations as a pivotal step in change; and assertive anger, self-soothing,
      hurt, and grief as states of advanced processing. Study 2 tested the model using
      a sample of 34 clients in global distress. A multivariate analysis of variance
      showed that the model of emotional processing predicted positive in-session
      effects, and bootstrapping analyses were used to demonstrate that distinct
      emotions emerged moment by moment in predicted sequential patterns.

PMID- 18085904
TI  - Shapes of early change in psychotherapy under routine outpatient conditions.
AB  - Although improvement of clients' state is a central concern for psychotherapy,
      relatively little is known about how change in outcome variables unfolds during
      psychotherapy. Client progress may follow highly variable temporal courses, and
      this variation in treatment courses may have important clinical implications. By
      analyzing treatment progress using growth mixture modeling up to the 6th session
      in a sample of 192 outpatients treated under routine clinic conditions, the
      authors identified 5 client groups based on similar progress on the short form
      versions of the Clinical Outcomes in Routine Evaluation-Outcome Measure. The
      shapes of early change typical for these client groups were characterized by (a)
      high initial impairment, (b) low initial impairment, (c) early improvement, (d)
      medium impairment with continuous treatment progress, or (e) medium impairment
      with discontinuous treatment progress. Moreover, the shapes of early change were
      associated with different treatment outcomes and durations, and several intake
      variables (depression, anxiety, and age) enabled prediction of the shape of early
      change and/or prediction of individual treatment progress within client groups
      with similar shapes of change.

PMID- 18085906
TI  - Recovery from major depressive disorder among female adolescents: a prospective
      test of the scar hypothesis.
AB  - This study examined the psychosocial consequences of experiencing major
      depressive disorder (MDD). In a 7-year longitudinal study of 496 female
      adolescents, the authors identified 49 girls who experienced their first episode
      of MDD and then recovered. They were compared with a randomly selected group of
      98 never depressed participants on 13 psychological, social, psychiatric, and
      life events variables. None of the variables fit the scar pattern (i.e., a group
      difference that emerges during the first MDD episode and remains elevated post
      recovery). All 13 variables were elevated before, during, and after the MDD
      episode, although some increased during the MDD episode. Results provide little
      support for the scar hypothesis among adolescent girls but instead suggest that
      many risk variables are elevated before and after the MDD episode. Interventions
      that modify these factors may help to reduce depression incidence and recurrence
      among female adolescents.

PMID- 18085907
TI  - A multisite investigation of binge eating behaviors in children and adolescents.
AB  - The phenomenology of childhood and adolescent loss of control (LOC) eating is
      unknown. The authors interviewed 445 youths to assess aspects of aberrant eating.
      LOC was associated with eating forbidden food before the episode; eating when not
      hungry; eating alone; and experiencing secrecy, negative emotions, and a sense of
      "numbing" while eating (ps<.01). Hierarchical cluster analysis revealed a
      subgroup, most of whom reported LOC eating. Cluster members reported having a
      trigger initiate episodes, eating while watching television, and having decreased
      awareness regarding the amount consumed. The authors conclude that aspects of LOC
      eating during youth are similar to aspects of adult episodes, but a youth
      specific presentation may exist. Findings may provide an intervening point to
      prevent excessive weight gain and eating disorders.

PMID- 18085908
TI  - A randomized controlled trial of a parent-centered intervention in preventing
      substance use and HIV risk behaviors in Hispanic adolescents.
AB  - The present study evaluated the efficacy of Familias Unidas + Parent
      Preadolescent Training for HIV Prevention (PATH), a Hispanic-specific, parent
      centered intervention, in preventing adolescent substance use and unsafe sexual
      behavior. Two hundred sixty-six 8th-grade Hispanic adolescents and their primary
      caregivers were randomly assigned to 1 of 3 conditions: Familias Unidas + PATH,
      English for Speakers of Other Languages (ESOL) + PATH, and ESOL + HeartPower! for
      Hispanics (HEART). Participants were assessed at baseline and at 6, 12, 24, and
      36 months postbaseline. Results showed that (a) Familias Unidas + PATH was
      efficacious in preventing and reducing cigarette use relative to both control
      conditions; (b) Familias Unidas + PATH was efficacious, relative to ESOL + HEART,
      in reducing illicit drug use; and (c) Familias Unidas + PATH was efficacious,
      relative to ESOL + PATH, in reducing unsafe sexual behavior. The effects of
      Familias Unidas + PATH on these distal outcomes were partially mediated by
      improvements in family functioning. These findings suggest that strengthening the
      family system, rather than targeting specific health behaviors, may be most
      efficacious in preventing and/or reducing cigarette smoking, illicit drug use,
      and unsafe sex in Hispanic adolescents.

PMID- 18085910
TI  - Insomnia and well-being.
AB  - Most Americans have occasional problems with insomnia. The relationship of
      insomnia to illness is well known. However, insomnia may also relate to lower
      levels of well-being. Although there are various definitions of well-being, one
      of the most clearly articulated and comprehensive models identifies 2 overarching
      constructs, psychological well-being and subjective well-being. The purpose in
      the present study was to assess the relationship between insomnia symptoms and
      the dimensions of psychological and subjective well-being, adjusting for the
      potential confound of comorbid physical and psychological illness. The data for
      the present study came from the National Survey of Midlife Development in the
      United States, a survey of community-dwelling adults. After adjustment for
      demographic characteristics and a wide range of chronic mental and physical
      health conditions, insomnia symptoms were found to have a significant
      relationship with both psychological and subjective well-being but a stronger
      relationship to subjective well-being. These data suggest that insomnia symptoms
      have a stronger relationship to enjoying life than to the perception that one has
      a meaningful life.

PMID- 18085909
TI  - RCT of a psychological intervention for patients with cancer: I. mechanisms of
      change.
AB  - Little is known about the therapeutic processes contributing to efficacy of
      psychological interventions for patients with cancer. Data from a randomized
      clinical trial yielding robust biobehavioral and health effects (B. L. Andersen
      et al., 2004, 2007) were used to examine associations between process variables,
      treatment utilization, and outcomes. Novel findings emerged. Patients were highly
      satisfied with the treatment, but their higher levels of felt support (group
      cohesion) covaried with lower distress and fewer symptoms. Also, specific
      treatment strategies were associated with specific outcomes, including lower
      distress, improved dietary habits, reduced symptomatology, and higher
      chemotherapy dose intensity. These data provide a comprehensive test of multiple
      therapeutic processes and mechanisms for biobehavioral change with an
      intervention including both intensive and maintenance phases.

PMID- 18085911
TI  - Day hospital and residential addiction treatment: randomized and nonrandomized
      managed care clients.
AB  - Male and female managed care clients randomized to day hospital (n=154) or
      community residential treatment (n=139) were compared on substance use outcomes
      at 6 and 12 months. To address possible bias in naturalistic studies, outcomes
      were also examined for clients who self-selected day hospital (n=321) and for
      clients excluded from randomization and directed to residential treatment because
      of high environmental risk (n=82). American Society of Addiction Medicine
      criteria defined study and randomization eligibility. More than 50% of followed
      clients reported past-30-day abstinence at follow-ups (unadjusted rates, not
      significant between groups). Despite differing baseline severities, randomized,
      self-selecting, and directed clients displayed similar abstinence outcomes in
      multivariate longitudinal models. Index treatment days and 12-step attendance
      were associated with abstinence (p<.001). Other prognostic effects (including
      gender and ethnicity) were not significant predictors of differences in outcomes
      for clients in the treatment modalities. Although 12-step attendance continued to
      be important for the full 12 months, treatment beyond the index stay was not,
      suggesting an advantage for engaging clients in treatment initially and promoting
      12-step attendance for at least a year.

PMID- 18085912
TI  - Sexuality and the commission of physical violence to partners and non-partners by
      men and women.
AB  - In 2 studies of physical violence and sexuality among college students, more than
      75% of men and more than 60% of women reported committing physical violence in
      the past year, including more women to partners and more men to non-partners.
      More than 90% of men who committed violence to partners were also violent to non
      partners. In Study 1, among 193 men and 203 women, people who committed violence
      had higher scores on sexual depression and general depression than did people who
      were not violent. People violent to non-partners had more sexual preoccupation
      and more alcohol use problems than did other people. In Study 2, among 160
      college men and 138 college women, people in 4 violence groups did not differ in
      total sexual fantasies or sexual functioning. The findings support the importance
      of differentiating between violence toward partners and toward non-partners among
      both men and women and suggest a role of depression in partner violence and
      antisocial features in violence toward non-partners.

PMID- 18085913
TI  - A randomized controlled trial comparing two vocational models for persons with
      severe mental illness.
AB  - The authors compared 2 approaches to vocational rehabilitation for individuals
      with severe mental illness: the individual placement and support (IPS) model of
      supported employment and the diversified placement approach (DPA), which
      emphasizes work readiness and offers a range of vocational options, including
      agency-run businesses and agency-contracted placements with community employers.
      In all, 187 unemployed participants with severe mental illness were randomly
      assigned to IPS or DPA. Over 2 years, IPS had significantly better competitive
      employment outcomes than DPA. Competitive employment rates over the 2-year follow
      up were 75.0% for IPS and 33.7% for DPA. However, IPS and DPA did not differ on
      paid employment outcomes. The authors conclude that IPS is more effective than
      DPA in achieving competitive employment, but not paid employment.

PMID- 18085914
TI  - Randomized trial of contingent prizes versus vouchers in cocaine-using methadone
      patients.
AB  - Contingency management (CM) interventions frequently utilize vouchers as
      reinforcers, but a prize-based system is also efficacious. This study compared
      these approaches. Seventy-four cocaine-dependent methadone outpatients were
      randomly assigned to standard treatment (ST), ST plus a maximum of $585 in
      contingent vouchers, or ST plus an expected average maximum of $300 in contingent
      prizes for 12 weeks. CM participants achieved longer durations of abstinence
      (LDA) than ST participants, and CM conditions did not differ significantly in
      outcomes or amount of reinforcement earned. Although long-term abstinence did not
      differ by group, LDA during treatment was the best predictor of abstinence at 9
      months. Thus, reinforcement with prizes was similar to voucher CM in promoting
      LDA, which is associated with posttreatment benefits.

PMID- 18085916
TI  - Mindfulness-based cognitive therapy: evaluating current evidence and informing
      future research.
AB  - Mindfulness-based cognitive therapy (MBCT) is a recently developed class-based
      program designed to prevent relapse or recurrence of major depression (Z. V.
      Segal, J. M. G. Williams, & J. Teasdale, 2002). Although research in this area is
      in its infancy, MBCT is generally discussed as a promising therapy in terms of
      clinical effectiveness. The aim of this review was to outline the evidence that
      contributes to this current viewpoint and to evaluate the strengths and
      weaknesses of this evidence to inform future research. By systematically
      searching 6 electronic databases and the reference lists of retrieved articles,
      the authors identified 4 relevant studies: 2 randomized clinical trials, 1 study
      based on a subset of 1 of these trials, and 1 nonrandomized trial. The authors
      evaluated these trials and discussed methodological issues in the context of
      future research. The current evidence from the randomized trials suggests that,
      for patients with 3 or more previous depressive episodes, MBCT has an additive
      benefit to usual care. However, because of the nature of the control groups,
      these findings cannot be attributed to MBCT-specific effects. Further research is
      necessary to clarify whether MBCT does have any specific effects.

PMID- 18085915
TI  - Ethnicity and mental health treatment utilization by patients with personality
      disorders.
AB  - The authors examined the relationship between ethnicity and treatment utilization
      by individuals with personality disorders (PDs). Lifetime and prospectively
      determined rates and amounts of mental health treatments received were compared
      in over 500 White, African American, and Hispanic participants with PDs in a
      naturalistic longitudinal study. Minority, especially Hispanic, participants were
      significantly less likely than White participants to receive a range of
      outpatient and inpatient psychosocial treatments and psychotropic medications.
      This pattern was especially pronounced for minority participants with more severe
      PDs. A positive support alliance factor significantly predicted the amount of
      individual psychotherapy used by African American and Hispanic but not White
      participants, underscoring the importance of special attention to the treatment
      relationship with minority patients. These treatment use differences raise
      complex questions about treatment assessment and delivery, cultural biases of the
      current diagnostic system, and possible variation in PD manifestation across
      racial/ethnic groups. Future studies need to assess specific barriers to adequate
      and appropriate treatments for minority individuals with PDs.

PMID- 18085917
TI  - Landmark-based search memory in the domestic dog (Canis familiaris).
AB  - Recent studies have suggested that any animal that relies on landmark-based
      search memory encodes and uses metric properties of space to navigate. So far,
      however, metric information provided by landmarks has been predominantly
      investigated in avian species. In the present study, I investigated whether the
      domestic dog (Canis familiaris), a mammalian species, encodes the distance and
      direction from landmarks. Dogs were trained to find a ball hidden next to an
      array of two distinct landmarks that remained at a constant location in a room
      from trial to trial. After training, the dogs were occasionally tested on
      unrewarded conditions where the array was either left in its usual position or
      shifted laterally, perpendicularly, or diagonally relative to the rear wall of
      the room. Although the dogs significantly shifted their search as a function of
      the displacement of the landmarks, they did not search at the predicted
      coordinates of the goal relative to the shift of the landmarks, suggesting that
      the global cues available in the testing room were also encoded and used by dogs
      to locate the position of the goal.

PMID- 18085918
TI  - Transfer of self-control in black (Eulemur macaco) and brown (Eulemur fulvus)
      lemurs: choice of a less preferred food item under a reverse-reward contingency.
AB  - When presented a choice between two food-type arrays of equivalent size under a
      reverse-reward contingency, black (Eulemur macaco) and brown (Eulemur fulvus)
      lemurs transposed their self-control abilities, acquired in a previous
      experiment, to significantly select the less-desired food item in order to gain
      access to the more desired one. However, when presented with the choice between
      two different food-type arrays in which the amount of the less desired food array
      was larger than the more desired one, large individual differences were revealed:
      Some subjects established a consistent rule favoring quality or quantity, whereas
      others exhibited various point of trade-off. These results show that lemurs seem
      to manage the task considering not only food quantity but also food quality.

PMID- 18085919
TI  - A comparative analysis of serial ordering in ring-tailed lemurs (Lemur catta).
AB  - Research over the last 25 years has demonstrated that animals are able to
      organize sequences in memory and retrieve ordered sequences without language.
      Qualitative differences have been found between the serial organization of
      behavior in pigeons and monkeys. Here the authors test serial ordering abilities
      in ring-tailed lemurs, a strepsirrhine primate whose ancestral lineage diverged
      from that of monkeys, apes, and humans approximately 63 million years ago.
      Lemurs' accuracy and response times were similar to monkeys, thus suggesting that
      they may share mechanisms for serial organization that dates to a common primate
      ancestor.

PMID- 18085920
TI  - Serial reversal learning and the evolution of behavioral flexibility in three
      species of North American corvids (Gymnorhinus cyanocephalus, Nucifraga
      columbiana, Aphelocoma californica).
AB  - In serial reversal learning, subjects learn to respond differentially to 2
      stimuli. When the task is fully acquired, reward contingencies are reversed,
      requiring the subject to relearn the altered associations. This alternation of
      acquisition and reversal can be repeated many times, and the ability of a species
      to adapt to this regimen has been considered as an indication of behavioral
      flexibility. Serial reversal learning of 2-choice discriminations was contrasted
      in 3 related species of North American corvids: pinyon jays (Gymnorhinus
      cyanocephalus), which are highly social; Clark's nutcrackers (Nucifraga
      columbiana), which are relatively solitary but specialized for spatial memory;
      and western scrub jays (Aphelocoma californica), which are ecological
      generalists. Pinyon jays displayed significantly lower error rates than did
      nutcrackers or scrub jays after reversal of reward contingencies for both spatial
      and color stimuli. The effect was most apparent in the 1st session following each
      reversal and did not reflect species differences in the rate of initial
      discrimination learning. All 3 species improved their performance over successive
      reversals and showed significant transfer between color and spatial tasks,
      suggesting a generalized learning strategy. The results are consistent with an
      evolutionary association between behavioral flexibility and social complexity.

PMID- 18085921
TI  - When, what, and whom to watch? Quantifying attention in ravens (Corvus corax) and
      jackdaws (Corvus monedula).
AB  - Complex social life requires monitoring of conspecifics. The amount and focus of
      attention toward others has been suggested to depend on the social relationships
      between individuals. Yet there are surprisingly few experiments that have tested
      these assumptions. This study compared attention patterns toward conspecifics in
      two corvid species, ravens (Corvus corax) and jackdaws (Corvus monedula). Birds
      were confronted with affiliated and non-affiliated conspecifics engaged in
      foraging and object manipulation. Visual access to the model bird was provided
      through two observation holes, which allowed measurement of exactly how often and
      for how long observers watched the other. Overall, ravens were more attentive to
      conspecifics than were jackdaws. Moreover, only ravens showed higher interest
      toward food-related than object-related behaviors of the model and toward close
      affiliates than non-affiliates by increasing the duration rather than the
      frequency of looks. These results are in accordance with predictions derived from
      the species' foraging biology and suggest that the facultative social, but highly
      manipulative, ravens use and value information from others differently than do
      the obligate social jackdaws.

PMID- 18085922
TI  - Generalization hypothesis of abstract-concept learning: learning strategies and
      related issues in Macaca mulatta, Cebus apella, and Columba livia.
AB  - The generalization hypothesis of abstract-concept learning was tested with a meta
      analysis of rhesus monkeys (Macaca mulatta), capuchin monkeys (Cebus apella), and
      pigeons (Columba livia) learning a same/different (S/D) task with expanding
      training sets. The generalization hypothesis states that as the number of
      training items increases, generalization from the training pairs will increase
      and could explain the subjects' accurate novel-stimulus transfer. By contrast,
      concept learning is learning the relationship between each pair of items; with
      more training items subjects learn more exemplars of the rule and transfer
      better. Having to learn the stimulus pairs (the generalization hypothesis) would
      require more training as the set size increases, whereas learning the concept
      might require less training because subjects would be learning an abstract rule.
      The results strongly support concept or rule learning despite severely relaxing
      the generalization-hypothesis parameters. Thus, generalization was not a factor
      in the transfer from these experiments, adding to the evidence that these
      subjects were learning the S/D abstract concept.

PMID- 18085923
TI  - Perceived differences between chimpanzee (Pan troglodytes) and human (Homo
      sapiens) facial expressions are related to emotional interpretation.
AB  - Human face perception is a finely tuned, specialized process. When comparing
      faces between species, therefore, it is essential to consider how people make
      these observational judgments. Comparing facial expressions may be particularly
      problematic, given that people tend to consider them categorically as emotional
      signals, which may affect how accurately specific details are processed. The
      bared-teeth display (BT), observed in most primates, has been proposed as a
      homologue of the human smile (J. A. R. A. M. van Hooff, 1972). In this study,
      judgments of similarity between BT displays of chimpanzees (Pan troglodytes) and
      human smiles varied in relation to perceived emotional valence. When a chimpanzee
      BT was interpreted as fearful, observers tended to underestimate the magnitude of
      the relationship between certain features (the extent of lip corner raise) and
      human smiles. These judgments may reflect the combined effects of categorical
      emotional perception, configural face processing, and perceptual organization in
      mental imagery and may demonstrate the advantages of using standardized
      observational methods in comparative facial expression research.

PMID- 18085924
TI  - Comparison of grouping abilities in humans (Homo sapiens) and baboons (Papio
      papio) with the Ebbinghaus illusion.
AB  - This research comparatively assessed grouping mechanisms of humans (n = 8) and
      baboons (n = 8) in an illusory task that employs configurations of target and
      surrounding circles arranged to induce the Ebbinghaus (Titchener) illusion.
      Analyses of response behaviors and points of subjective equality demonstrated
      that only humans misjudged the central target size under the influence of the
      Ebbinghaus illusion, whereas baboons expressed a more veridical perception of
      target sizes. It is argued that humans adopted a global mode of stimulus
      processing of the illusory figure in our task that has favored the illusion. By
      contrast, a strong local mode of stimulus processing with attention restricted to
      the target must have prevented illusory effects in baboons. These findings
      suggest that monkeys and humans have evolved modes of object recognition that do
      not similarly rely on the same gestalt principles.

PMID- 18085925
TI  - Spatial learning and memory in the tortoise (Geochelone carbonaria).
AB  - A single tortoise (Geochelone carbonaria) was trained in an eight-arm radial
      maze, with the apparatus and general procedures modeled on those used to
      demonstrate spatial learning in rats. The tortoise learned to perform reliably
      above chance, preferentially choosing baited arms, rather than returning to arms
      previously visited on a trial. Test sessions that examined control by olfactory
      cues revealed that they did not affect performance. No systematic, stereotyped
      response patterns were evident. In spite of differences in brain structure, the
      tortoise showed spatial learning abilities comparable to those observed in
      mammals.

PMID- 18085926
TI  - Common toads (Bufo arenarum) learn to anticipate and avoid hypertonic saline
      solutions.
AB  - Toads (Bufo arenarum) were exposed to pairings between immersion in a neutral
      saline solution (i.e., one that caused no significant variation in fluid
      balance), followed by immersion in a highly hypertonic saline solution (i.e., one
      that caused water loss). In Experiment 1, solutions were presented in a Pavlovian
      conditioning arrangement. A group receiving a single neutral-highly hypertonic
      pairing per day exhibited a greater conditioned increase in heart rate than
      groups receiving either the same solutions in an explicitly unpaired fashion, or
      just the neutral solution. Paired toads also showed a greater ability to
      compensate for water loss across trials than that of the explicitly unpaired
      group. Using the same reinforcers and a similar apparatus, Experiment 2
      demonstrated that toads learn a one-way avoidance response motivated by immersion
      in the highly hypertonic solution. Cardiac and avoidance conditioning are
      elements of an adaptive system for confronting aversive situations involving loss
      of water balance.

PMID- 18085927
TI  - Pitch perception in chinchillas (Chinchilla laniger): stimulus generalization
      using rippled noise.
AB  - Rippled noises evoke the perception of pitch in human listeners. Infinitely
      iterated rippled noise (IIRN) is generated when wideband noise (WBN) is delayed,
      attenuated, and added to the original WBN through either a positive (+) or a
      negative (-) feedback loop. The pitch of IIRN[+] is matched to the reciprocal of
      the delay, whereas the pitch of IIRN[-] for the same delay is an octave lower.
      Chinchillas (Chinchilla laniger) were trained to discriminate IIRN[+] with a 4-ms
      delay from IIRN[+] with a 2-ms delay and then tested in a stimulus generalization
      paradigm with IIRN[+] at delays between 2 and 4 ms. Systematic gradients in
      behavioral response occurred along the dimension of delay, suggesting that a
      perceptual dimension corresponding to pitch exists for IIRN[+]. Behavioral
      responses to IIRN[-] test stimuli were more variable among chinchillas,
      suggesting that IIRN[-] did not evoke similar pitches relative to IIRN[+].
      Systematic gradients in behavioral response were observed when IIRN[-] test
      stimuli were presented in the context of other IIRN[-] stimuli. Thus, other
      perceptual cues such as timbre may dominate the pitch cues when IIRN[-] test
      stimuli are presented in the context of IIRN[+] stimuli.

PMID- 18085928
TI  - Responses of dairy heifers to the visual cliff formed by a herringbone milking
      pit: evidence of fear of heights in cows (Bos taurus).
AB  - The ability of cows (Bos taurus) to perceive depth has never been experimentally
      investigated. If cows can perceive depth, the milking pit in commercial milking
      facilities may be fear provoking for dairy cows, as past research has shown that
      most land-dwelling species possess an instinctive fear of heights. In the current
      study, 12 dairy heifers (1-year-old cows) were exposed to a milking pit (depth
      exposed group) and 13 heifers (control group) were exposed to a standard change
      in the environment while they moved through a milking facility over a 5-day
      treatment period. Heifers in the depth-exposed group showed a higher heart rate
      (p < .05) and stopped more often (p < .05) than did those in the control group;
      persistence of heart rate but not of behavioral responses on repeated exposures
      indicated that some habituation to the depth stimulus had occurred. Depth
      exposure had no effect on cortisol concentrations or on ease of handling. These
      results indicate that heifers responded differently to a change in depth than
      they did to a standard change in the environment and provide evidence of both
      depth perception and acute fear of heights in cows.

PMID- 18085929
TI  - Learning to learn during visual discrimination in group housed dwarf goats (Capra
      hircus).
AB  - Using an automated learning device, we investigated "learning to learn" by dwarf
      goats (Capra hircus) in what was for them a familiar environment and normal
      social settings. Nine problems, each consisting of four discriminable black
      symbols, each with one S-super+ and three different S-super(-), were presented on
      a computer screen. Mean daily learning success improved over the course of the
      first four problems, and the improvement was maintained throughout the remaining
      five problems. The number of trials to reach the learning criterion decreased
      significantly beginning with problem four. Such results may be interpreted as
      evidence that the goats were developing a learning set. In the present case, the
      learning set appeared to have two components. One involved gaining familiarity
      and apparent understanding of the learning device and the basic requirements of
      the discrimination task. The second component involved learning potential error
      factors to be ignored, as well as learning commonalities that carried over from
      one problem to the next. Among the error factors, evidence of apparent
      preferences for specific symbols was seen, which had a predictable effect on
      performances.

PMID- 18085930
TI  - Psychometric properties of the State-Trait Inventory for Cognitive and Somatic
      Anxiety (STICSA): comparison to the State-Trait Anxiety Inventory (STAI).
AB  - The State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA; M. J. Ree,
      C. MacLeod, D. French, & V. Locke, 2000) was designed to assess cognitive and
      somatic symptoms of anxiety as they pertain to one's mood in the moment (state)
      and in general (trait). This study extended the previous psychometric findings to
      a clinical sample and validated the STICSA against a well-published measure of
      anxiety, the State-Trait Anxiety Inventory (STAI; C. D. Spielberger, 1983).
      Patients (N=567) at an anxiety disorders clinic were administered a battery of
      questionnaires. The results of confirmatory factor analyses (Bentler-Bonnett
      nonnormed fit index, comparative fit index, and Bollen fit index>.90; root-mean
      square error of approximation<.05); convergent and discriminant validity
      analyses; and group comparisons supported the reliability and validity of the
      STICSA as a measure of state and trait cognitive and somatic anxiety. In
      addition, compared with the STAI (anxiety: rs</=.52; depression: rs>/=.64), the
      STICSA was more strongly correlated with another measure of anxiety (rs>/=.67)
      and was less strongly correlated with a measure of depression (rs</=.61). These
      findings suggest that the STICSA may be a purer measure of anxiety symptomatology
      than is the STAI.

PMID- 18085931
TI  - Validation of a self-report measure of unrealistic relationship expectations.
AB  - Cognitive models of intimate partner aggression implicate maladaptive
      relationship beliefs as antecedents to aggression and targets for intervention.
      However, existing self-report measures of relationship beliefs have failed to
      differentiate aggressive and nonaggressive individuals, raising questions about
      their assessment of and role in understanding aggression. To address these
      concerns, the authors developed and tested a new measure of unrealistic
      relationship beliefs in a sample of 453 community couples. Structural validity,
      concurrent validity, discriminant validity, internal consistency, and temporal
      stability of the new measure were examined. The final scale demonstrated adequate
      internal consistency (alphas=.83-.84), test-retest reliability (rs=.68-.74), and
      concurrent validity (small to moderate associations with predicted variables).
      Unrealistic relationship beliefs significantly differentiated aggressive and
      nonaggressive men, and this association remained significant after the authors
      controlled for other related variables.

PMID- 18085933
TI  - The Couples Emotion Rating Form: psychometric properties and theoretical
      associations.
AB  - The Couples Emotion Rating Form assesses 3 types of negative emotion that are
      salient during times of relationship conflict. Hard emotion includes feeling
      angry and aggravated, soft emotion includes feeling hurt and sad, and flat
      emotion includes feeling bored and indifferent. In Study 1, scales measuring hard
      and soft emotion were validated by observation of 82 married couples in a series
      of conflict conversations. Self-report ratings for each emotion corresponded with
      observer ratings of the same emotion, and the emotion scales produced expected
      correlations with negative affect. In Study 2, a measure of flat emotion was
      added to the instrument, and 1,239 married people completed questionnaires. The
      rating form fit an expected 3-dimensional factor structure, and each scale
      correlated with a set of theoretically linked constructs. Hard emotion was
      associated with power assertion, pursuit of self-centered goals, and negative
      communication. Soft emotion was associated with expressions of vulnerability,
      pursuit of prosocial goals, and positive communication. Flat emotion was distinct
      from other emotions in being associated with withdrawal.

PMID- 18085932
TI  - Assessing relationship quality in mandated community treatment: blending care
      with control.
AB  - Traditional measures of the therapeutic alliance do not capture the dual roles
      inherent in relationships with involuntary clients. Providers not only care for,
      but also have control over, involuntary clients. In 2 studies of probationers
      mandated to psychiatric treatment (n=90; n=322), the authors developed and
      validated the revised Dual-Role Relationships Inventory (DRI-R). The authors
      found that (a) relationship quality in mandated treatment involves caring and
      fairness, trust, and an authoritative (not authoritarian) style, (b) the DRI-R
      assesses these domains of relationship quality, is internally consistent, and
      relates in a theoretically coherent pattern with ratings of within-session
      behavior and with measures of the therapeutic alliance, relationship
      satisfaction, symptoms, and treatment motivation, and (c) the quality of dual
      role relationships predicts future compliance with the rules, as assessed by
      probation violations and revocation. The DRI-R covaries with multiple domains
      more strongly than a leading measure of the therapeutic alliance, suggesting that
      it better captures the nature and effect of relationship quality in mandated
      treatment.

PMID- 18085934
TI  - Predictive validity of the Chinese version of the Adult Suicidal Ideation
      Questionnaire: psychometric properties and its short version.
AB  - The success of screening for individuals at suicidal risk among the general
      population relies heavily on the availability of a reliable and validated
      instrument. However, there remains a lack of a well-validated screening tool for
      suicidal risk in Chinese, despite the fact that about a quarter of the world's
      suicides takes place in China. In view of the severity of the suicide problem
      among the Chinese population, there is a crucial need to develop robust screening
      tools locally. This study investigates the psychometric properties related to the
      Chinese version of the Adult Suicidal Ideation Questionnaire (ASIQ) with a 2
      wave, population-based panel study in the Hong Kong Special Administrative
      Region, People's Republic of China. Two-thousand sixteen Chinese people were
      interviewed for their suicidality, psychological well-being, and ASIQ scores. The
      Chinese ASIQ was shown to have strong internal reliability, convergent validity,
      and factorial validity. This study also demonstrated its predictive validity by
      examining sensitivity and specificity in identifying subsequent suicidality. A 4
      item short version of ASIQ was also developed.

PMID- 18085935
TI  - A comparison of MMPI--2 measures of psychopathic deviance in a forensic setting.
AB  - We examined the convergent and discriminant validity of the Minnesota Multiphasic
      Personality Inventory--2 (MMPI--2) measures of psychopathy, including the
      Clinical Scale 4, Restructured Clinical Scale 4 (RC4), Content Scale Antisocial
      Practices (ASP), and Personality Psychopathology Five Scale Disconstraint (DISC).
      Comparisons of the empirical correlates of these scales were conducted with 2
      samples of participants evaluated at a criminal court clinic. The 2 samples
      included 59 men and 19 women and 913 men and 327 women, respectively. Two types
      of criteria (clinician ratings and archival record review) were utilized in the
      analyses. Relative to Clinical Scale 4, RC4 had significantly greater convergent
      validity in predicting psychopathy as measured by the Psychopathy Checklist-
      Screening Version (S. D. Hart, D. N. Cox, & R. D. Hare, 1995) and behavioral
      criteria associated with this construct. RC4 also showed substantially improved
      discriminant validity when compared with its Clinical Scale counterpart. Among
      all the MMPI-2 scales studied, RC4 was the best measure of the social deviance
      traits of psychopathy.

PMID- 18085936
TI  - A taxometric study of the latent structure of disgust sensitivity: converging
      evidence for dimensionality.
AB  - Disgust sensitivity has recently been implicated as a specific vulnerability
      factor for several anxiety-related disorders. However, it is not clear whether
      disgust sensitivity is a dimensional or categorical phenomenon. The present study
      examined the latent structure of disgust by applying three taxometric procedures
      (maximum eigenvalue, mean above minus below a cut, and latent-mode factor
      analysis) to data collected from 2 large nonclinical samples on 2 different
      measures of disgust sensitivity. Disgust sensitivity in the first sample
      (n=1,153) was operationalized by disgust reactions to food, animals, body
      products, sex, body envelope violations, death, hygiene, and sympathetic magic,
      as assessed by the Disgust Sensitivity Scale (J. Haidt, C. McCauley, & P. Rozin,
      1994). Disgust Sensitivity Scale indicators of core, animal reminder, and
      contamination disgust were also examined in the 1st sample. Disgust sensitivity
      in the 2nd independent sample (n=1,318) was operationalized by disgust reactions
      to animals, injections and blood draws, mutilation and death, rotting foods, and
      odors, as assessed by the Disgust Emotion Scale (R. A. Kleinknecht, E. E.
      Kleinknecht, & R. M. Thorndike, 1997). Results across both samples provide
      converging evidence that disgust sensitivity is best conceptualized as a
      dimensional construct, present to a greater or lesser extent in all individuals.
      These findings are discussed in relation to the conceptualization and assessment
      of disgust sensitivity as a specific dimensional vulnerability for certain
      anxiety and related disorders.

PMID- 18085937
TI  - Are dietary restraint scales valid measures of moderate- to long-term dietary
      restriction? Objective biological and behavioral data suggest not.
AB  - Prospective studies indicate that elevated scores on dietary restraint scales
      predict bulimic symptom onset, but experiments indicate that assignment to
      dietary restriction interventions reduces bulimic symptoms. One possible
      explanation for the inconsistent findings is that the dietary restraint scales
      used in the former studies are not valid measures of dietary restriction. The
      authors previously found that dietary restraint scales were not inversely
      correlated with objective measures of short-term caloric intake (E. Stice, M.
      Fisher, & M. R. Lowe, 2004). In this follow-up report, 3 studies indicated that
      the Three-Factor Eating Questionnaire dietary restraint scale was not correlated
      with doubly labeled water estimated energy intake over 2-week periods or with
      observationally measured caloric intake over 3 months. Results from this study
      and others suggest that dietary restraint scales may not be valid measures of
      moderate- to long-term dietary restriction and imply the need to reinterpret
      findings from studies that have used dietary restraint scales.

PMID- 18085938
TI  - An investigation of the measurement properties of the Spot-the-Word test in a
      community sample.
AB  - Intellectual ability is assessed with the Spot-the-Word (STW) test (A. Baddeley,
      H. Emslie, & I. Nimmo Smith, 1993) by asking respondents to identify a word in a
      word-nonword item pair. Results in moderate-sized samples suggest this ability is
      resistant to decline due to dementia. The authors used a 3-parameter item
      response theory model to investigate the measurement properties of the STW in a
      large community-dwelling sample (n=2,480) 60 to 64 years of age. A number of
      poorly performing items were identified. Substantial guessing was present;
      however, the number of words correctly identified was found to be an accurate
      index of ability. Performance was moderately related to a number of tests of
      cognitive performance and was effectively unrelated to visual acuity and to
      physical or mental health status. The STW is a promising test of ability that, in
      the future, may be refined by the deletion or replacement of poorly functioning
      items.

PMID- 18085939
TI  - Detecting back irrelevant responding on the Personality Assessment Inventory in a
      psychiatric inpatient setting.
AB  - The present studies focus on strategies for detecting back irrelevant responding
      (BIR) on the Personality Assessment Inventory (PAI; L. C. Morey, 1991). Moderate
      BIR levels can greatly affect the clinical scales of the PAI. Further, the PAI's
      Inconsistency and Infrequency validity scales are less than optimal for detecting
      BIR. L. C. Morey and C. J. Hopwood (2004) developed an alternative strategy for
      detecting BIR that involves comparison of 2 scales from the PAI short-form with
      the same 2 scales from the PAI full-instrument. The present study examines how
      different BIR levels affect the clinical, treatment, and interpersonal scales of
      the PAI in 2 psychiatric inpatient samples. The effectiveness of various
      strategies for detecting BIR in an inpatient setting is also discussed.
      Consistent with previous research, moderate rates of BIR impacted several PAI
      scales in a meaningful way. The Inconsistency and Infrequency validity scales of
      the PAI were relatively ineffective for detecting low-to-moderate BIR levels.
      Conversely, the short-form full-instrument comparison strategy was much more
      sensitive to BIR. Finally, a new BIR detection indicator is presented that
      improves sensitivity rates for detecting all BIR levels in an acute setting. The
      implications of these results for detecting BIR in inpatient settings are
      discussed.

PMID- 18085940
TI  - Predicting future reconviction in offenders with intellectual disabilities: the
      predictive efficacy of VRAG, PCL-SV, and the HCR-20.
AB  - Accurate predictions of future reconviction, including those for violent crimes,
      have been shown to be greatly aided by the use of formal risk assessment
      instruments. However, it is unclear as to whether these instruments would also be
      predictive in a sample of offenders with intellectual disabilities. In this
      study, the authors have shown that the Violence Risk Appraisal Guide (V. L.
      Quinsey, G. T. Harris, M. E. Rice, & C. Cormier, 1998); the Psychopathy Checklist
      -Screening Version (S. D. Hart, D. N. Cox, & R. D. Hare, 1995); and the History,
      Clinical, Risk Management--20 (C. D. Webster, K. S. Douglas, D. Eaves, & S. D.
      Hart, 1997) were all significant predictors of violent and general reconviction
      in this sample, and in many cases, their efficacy was greater than in a control
      sample of mentally disordered offenders without an intellectual disability.

PMID- 18085941
TI  - Agency, subjective time, and other minds.
AB  - Intentional binding refers to a temporal attraction in the perceived times of
      actions and effects. So far, it has solely been investigated using judgments of
      the perceived time of actions or their effects. The authors report 3 experiments
      using an alternative method: the estimation of a time interval between a
      voluntary action and its subsequent effect. Interval estimates were obtained for
      intervals bounded by different kinds of actions and effects: The actions were
      either performed by the participants themselves or by the experimenter. The
      effects, in turn, were movements either applied to the body of the participant or
      to the experimenter. First, the results validated interval estimation as a method
      for exploring action awareness. Second, intentional binding was stronger for self
      generated compared with observed actions, indicating that private information
      about the action contributes to action awareness. In contrast, intentional
      binding did not depend on whether a somatic effect was applied to the
      participant's or to another person's body. Third, for self-generated actions,
      external events gave rise to a stronger intentional binding than did somatic
      effects. This finding indicates that intentional binding especially links actions
      with their consequences in the external world.

PMID- 18085942
TI  - Response coding and visuomotor transformation in the Simon task: the role of
      action goals.
AB  - Manual responses can be defined by differing response parameters. Any of them may
      generate a Simon effect. For all those response parameters, the same
      implementation of the Simon effect (in terms of subserving mechanism) is assumed.
      In 3 experiments, subjects had to respond with either fingers or sticks. Temporal
      properties of the Simon effect changed with response parameters relevant in a
      task. The Simon effect for manual responses decayed. For stick responses, in
      which the action goal differed from the anatomical mapping of the acting hand, a
      sustained Simon effect was observed. However, if the action goal for stick
      responses was not instrumental for selecting the correct response, the Simon
      effect decayed. The findings are consistent with the notion of different
      mechanisms involved in generating a Simon effect.

PMID- 18085943
TI  - Contrast adaptation implies two spatiotemporal channels but three adapting
      processes.
AB  - The contrast gain control model of adaptation predicts that the effects of
      contrast adaptation correlate with contrast sensitivity. This article reports
      that the effects of high contrast spatiotemporal adaptors are maximum when
      adapting around 19 Hz, which is a factor of two or more greater than the peak in
      contrast sensitivity. To explain the discrepancy, the predictions made by
      parallel versus cascaded models of spatiotemporal processing are compared. It is
      demonstrated that a parallel two-temporal channel model, in which the adaptive
      attenuation of a channel is proportional to its response, cannot explain the
      effects of adaptation on threshold contrast but that a cascaded model can. The
      cascaded model suggests that the visual system temporally encodes spatiotemporal
      signals via an adaptive transient encoding process that lies in cascade with an
      adaptable two-temporal channel system of sustained versus transient processes.

PMID- 18085944
TI  - No-onset looming motion guides spatial attention.
AB  - These 6 experiments explored the ability of moving random dot patterns to attract
      attention, as measured by a simple probe-detection task. Each trial began with
      random motion (i.e., dots linearly moved in random directions). After 1 s motion
      in 1 hemifield became gradually coherent (i.e., all dots moved up-, down-, left-,
      or rightwards, or either towards or away from a vanishing point). The results
      show that only looming motion attracted attention, even when the task became a
      more demanding discrimination task. This effect is not due to an apparent
      magnification of stimuli presented in the focus of expansion. When the coherent
      motion started abruptly, all types of motion attracted attention at a short
      stimulus onset asynchrony. The looming motion effect only disappeared when
      attention was drawn to the target location by an arrow. These results suggest
      that looming motion plays a unique role in guiding spatial attention.

PMID- 18085945
TI  - Multisensory cues capture spatial attention regardless of perceptual load.
AB  - We compared the ability of auditory, visual, and audiovisual (bimodal) exogenous
      cues to capture visuo-spatial attention under conditions of no load versus high
      perceptual load. Participants had to discriminate the elevation (up vs. down) of
      visual targets preceded by either unimodal or bimodal cues under conditions of
      high perceptual load (in which they had to monitor a rapidly presented central
      stream of visual letters for occasionally presented target digits) or no
      perceptual load (in which the central stream was replaced by a fixation point).
      The results of 3 experiments showed that all 3 cues captured visuo-spatial
      attention in the no-load condition. By contrast, only the bimodal cues captured
      visuo-spatial attention in the high-load condition, indicating for the first time
      that multisensory integration can play a key role in disengaging spatial
      attention from a concurrent perceptually demanding stimulus.

PMID- 18085946
TI  - Inhibition of return and object-based attentional selection.
AB  - Visual attention research has revealed that attentional allocation can occur in
      space- and/or object-based coordinates. Using the direct and elegant design of R.
      Egly, J. Driver, and R. Rafal (1994), the present experiments tested whether
      space- and object-based inhibition of return (IOR) emerge under similar time
      courses. The experiments were capable of isolating both space- and object-based
      effects induced by peripheral and back-to-center cues. The results generally
      support the contention that spatially nonpredictive cues are effective in
      producing space-based IOR at a variety of stimulus onset asynchronies (SOAs) and
      under a variety of stimulus conditions. Whether facilitatory or inhibitory in
      direction, the object-based effects occurred over a very different time course
      than did the space-based effects. Reliable object-based IOR was only found under
      limited conditions and was tied to the time since the most recent cue (peripheral
      or central). The finding that object-based effects are generally determined by
      SOA from the most recent cue may help to resolve discrepancies in the IOR
      literature. These findings also have implications for the search facilitator role
      that IOR is purported to play in the guidance of visual attention.

PMID- 18085947
TI  - The role of spatial and nonspatial information in visual selection.
AB  - Even though it is undisputed that prior information regarding the location of a
      target affects visual selection, the issue of whether information regarding
      nonspatial features, such as color and shape, has similar effects has been a
      matter of debate since the early 1980s. In the study described in this article,
      measures derived from signal detection theory were used to show that perceptual
      sensitivity is affected by a top-down set for spatial information but not by a
      top-down set for nonspatial information. This indicates that knowing where the
      target singleton is affects perceptual selectivity but that knowing what it is
      does not help selectivity. Furthermore, perceptual sensitivity can be enhanced by
      nonspatial features, but only through a process related to bottom-up priming.
      These findings have important implications for models of visual selection.

PMID- 18085948
TI  - Trade-offs between gaze and working memory use.
AB  - Eye movements during natural tasks suggest that observers do not use working
      memory to capacity but instead use eye movements to acquire relevant information
      immediately before needed. Results here however, show that this strategy is
      sensitive to memory load and to observers' expectations about what information
      will be relevant. Depending upon the predictability of what object features would
      be needed in a brick sorting task, subjects spontaneously modulated the order in
      which they sampled and stored visual information using working memory more when
      the task was predictable and reverting to a just-in-time strategy when the task
      was unpredictable and the memory load was higher. This self organization was
      evidenced by subjects' sequence of eye movements and also their sorting decisions
      following missed feature changes. These results reveal that attentional
      selection, fixations, and use of working memory reflect a dynamic optimization
      with respect to a set of constraints, such as task predictablity and memory load.
      They also reveal that change blindness depends critically on the local task
      context, by virtue of its influence on the information selected for storage in
      working memory.

PMID- 18085949
TI  - Nonconscious control mimics a purposeful strategy: strength of Stroop-like
      interference is automatically modulated by proportion of compatible trials.
AB  - The magnitude of the Stroop effect is known to be modulated by the proportion of
      trials on which the irrelevant word and relevant ink color correspond. This has
      often been attributed to a conscious strategy of increased (or decreased)
      reliance on the irrelevant words when these are more likely (or less likely) to
      correspond to the ink colors. However, the present data from a Stroop-like task
      involving successively presented arrows indicate instead that this type of
      modulation can be automatic because it can occur even if the irrelevant stimuli
      are not phenomenally visible. In this case participants cannot determine the
      proportion of compatible trials to direct their strategy. An automatic, item
      specific associative interpretation can account for these findings.

PMID- 18085950
TI  - Developmental dissociations of preparation over time: deconstructing the variable
      foreperiod phenomena.
AB  - In a variable foreperiod (FP) paradigm, reaction times (RTs) decrease as a
      function of FP on trial n (FP effect) but increase with FP on trial n - 1
      (sequential effects). These phenomena have traditionally been ascribed to
      different strategic preparation processes. According to an alternative
      explanation, common conditioning laws underlie both effects. The present study
      aims to disentangle these opposite views using a developmental perspective. In
      Experiment 1A, 4- to 11-year-old children and a control group of adults performed
      a simple RT task with variable FPs (1, 3, and 5 s). Furthermore, 12 4- to 5-year
      old children were retested after 14 months (Experiment 1B). In Experiment 2, a
      narrower pool of participants (4, 5, and 6 years old) performed a variable FP
      paradigm with different FPs (1, 2, and 3 s). The results consistently suggest
      different ontogenetic time courses for the two effects: The sequential effects
      are already present in the youngest group (4-5 years old), whereas the FP effect
      appears gradually some years later. These findings are not fully compatible with
      previous views. A dual-process account is proposed to explain the data.

PMID- 18085951
TI  - The role of eye movements in subitizing and counting.
AB  - Previous work has suggested that eye movements may be necessary for accurate
      enumeration beyond the subitization range of about 4 items. This study determined
      the frequency of eye movements normally made during enumeration, their
      relationship to response times, and whether they are required for accurate
      performance. This was achieved by monitoring eye movements and comparing
      performance when observers were allowed to saccade and when they were not. The
      results showed that (a) there was a sharp increase in saccadic frequency beyond
      about 4 items (from < 0.2 saccades per item to about 1 per item), and (b)
      enumeration of fewer than 4 items remained rapid and accurate even when eye
      movements were prevented, whereas enumeration beyond this became less efficient
      and sometimes less accurate. The results are discussed in relation to the memory
      and processing requirements of enumeration tasks.

PMID- 18085952
TI  - Getting a grip on numbers: numerical magnitude priming in object grasping.
AB  - To investigate the functional connection between numerical cognition and action
      planning, the authors required participants to perform different grasping
      responses depending on the parity status of Arabic digits. The results show that
      precision grip actions were initiated faster in response to small numbers,
      whereas power grips were initiated faster in response to large numbers. Moreover,
      analyses of the grasping kinematics reveal an enlarged maximum grip aperture in
      the presence of large numbers. Reaction time effects remained present when
      controlling for the number of fingers used while grasping but disappeared when
      participants pointed to the object. The data indicate a priming of size-related
      motor features by numerals and support the idea that representations of numbers
      and actions share common cognitive codes within a generalized magnitude system.

PMID- 18085953
TI  - The mental representation of numerical fractions: real or integer?
AB  - Numerical fractions are commonly used to express ratios and proportions (i.e.,
      real numbers), but little is known about how they are mentally represented and
      processed by skilled adults. Four experiments employed comparison tasks to
      investigate the distance effect and the effect of the spatial numerical
      association of response codes (SNARC) for fractions. Results showed that
      fractions were processed componentially and that the real numerical value of the
      fraction was not accessed, indicating that processing the fraction's magnitude is
      not automatic. In contrast, responses were influenced by the numerical magnitude
      of the components and reflected the simple comparison between numerators,
      denominators, and reference, depending on the strategy adopted. Strategies were
      used even by highly skilled participants and were flexibly adapted to the
      specific experimental context. In line with results on the whole number bias in
      children, these findings suggest that the understanding of fractions is rooted in
      the ability to represent discrete numerosities (i.e., integers) rather than real
      numbers and that the well-known difficulties of children in mastering fractions
      are circumvented by skilled adults through a flexible use of strategies based on
      the integer components.

PMID- 18085954
TI  - Dissociating averageness and attractiveness: attractive faces are not always
      average.
AB  - Although the averageness hypothesis of facial attractiveness proposes that the
      attractiveness of faces is mostly a consequence of their averageness, 1 study has
      shown that caricaturing highly attractive faces makes them mathematically less
      average but more attractive. Here the authors systematically test the averageness
      hypothesis in 5 experiments using both rating and visual adaptation paradigms.
      Visual adaptation has previously been shown to increase both preferences for
      previously viewed face types (i.e., attractiveness) and their perceived normality
      (i.e., averageness). The authors used a visual adaptation procedure to test
      whether facial attractiveness is dependent upon faces' proximity to average
      (averageness hypothesis) or their location relative to average along an
      attractiveness dimension in face space (contrast hypothesis). While the typical
      pattern of change due to visual adaptation was found for judgments of normality,
      judgments of attractiveness resulted in a very different pattern. The results of
      these 5 experiments conclusively support the proposal that there are specific
      nonaverage characteristics that are particularly attractive. The authors discuss
      important implications for the interpretation of studies using a visual
      adaptation paradigm to investigate attractiveness.

PMID- 18085955
TI  - The importance of information localization in scene gist recognition.
AB  - People can recognize the meaning or gist of a scene from a single glance, and a
      few recent studies have begun to examine the sorts of information that contribute
      to scene gist recognition. The authors of the present study used visual masking
      coupled with image manipulations (randomizing phase while maintaining the Fourier
      amplitude spectrum; random image structure evolution [RISE]; J. Sadr & P. Sinha,
      2004) to explore whether and when unlocalized Fourier amplitude information
      contributes to gist perception. In 4 experiments, the authors found that
      differences between scene categories in the Fourier amplitude spectrum are
      insufficient for gist recognition or gist masking. Whereas the global 1/f spatial
      frequency amplitude spectra of scenes plays a role in gist masking, local phase
      information is necessary for gist recognition and for the strongest gist masking.
      Moreover, the ability to recognize the gist of a target image was influenced by
      mask recognizability, suggesting that conceptual masking occurs even at the
      earliest stages of scene processing.

PMID- 18085956
TI  - Configural response learning: the acquisition of a nonpredictive motor skill.
AB  - This study examined the representational nature of configural response learning
      using a task that required simultaneous keypresses with 2 or 3 fingers, similar
      to the production of chords on the piano. If the benefits of learning are related
      to the retrieval of individual stimulus-response mappings, performance should
      depend on the frequencies of the individual responses forming each chord.
      Alternatively, learning may involve the encoding of configural information
      concerning the relationship between the chord elements. In Experiment 1, training
      was restricted to a subset of the 120 possible 3-element chords. Probe blocks
      included the practiced chords, chords composed of novel configurations of
      practiced elements (reconfigured), and chords that contained a new element (new).
      Practiced chords were performed faster than reconfigured chords, indicating
      learning involves the encoding of configural information. Experiment 2 showed
      that learning was not restricted to configurations within each hand. Experiments
      3 and 4 demonstrated that learning was largely response based.

PMID- 18085957
TI  - Erroneous knowledge of results affects decision and memory processes on timing
      tasks.
AB  - On mental timing tasks, erroneous knowledge of results (KR) leads to incorrect
      performance accompanied by the subjective judgment of accurate performance. Using
      the start-stop technique (an analogue of the peak interval procedure) with both
      reproduction and production timing tasks, the authors analyze what processes
      erroneous KR alters. KR provides guidance (performance error information) that
      lowers decision thresholds. Erroneous KR also provides targeting information that
      alters response durations proportionately to the magnitude of the feedback error.
      On the production task, this shift results from changes in the reference memory,
      whereas on the reproduction task this shift results from changes in the decision
      threshold for responding. The idea that erroneous KR can alter different
      cognitive processes on related tasks is supported by the authors' demonstration
      that the learned strategies can transfer from the reproduction task to the
      production task but not visa versa. Thus effects of KR are both task and context
      dependent.

PMID- 18085958
TI  - Recalibration of phonetic categories by lipread speech versus lexical
      information.
AB  - Listeners hearing an ambiguous phoneme flexibly adjust their phonetic categories
      in accordance with information telling what the phoneme should be (i.e.,
      recalibration). Here the authors compared recalibration induced by lipread versus
      lexical information. Listeners were exposed to an ambiguous phoneme halfway
      between /t/ and /p/ dubbed onto a face articulating /t/ or /p/ or embedded in a
      Dutch word ending in /t/ (e.g., groot [big]) or /p/ (knoop [button]). In a
      posttest, participants then categorized auditory tokens as /t/ or /p/. Lipread
      and lexical aftereffects were comparable in size (Experiment 1), dissipated about
      equally fast (Experiment 2), were enhanced by exposure to a contrast phoneme
      (Experiment 3), and were not affected by a 3-min silence interval (Experiment 4).
      Exposing participants to 1 instead of both phoneme categories did not make the
      phenomenon more robust (Experiment 5). Despite the difference in nature (bottom
      up vs. top-down information), lipread and lexical information thus appear to
      serve a similar role in phonetic adjustments.

PMID- 18085959
TI  - Recovery from object substitution masking induced by transient suppression of
      visual motion processing: a repetitive transcranial magnetic stimulation study.
AB  - Object substitution masking is a form of visual backward masking in which a
      briefly presented target is rendered invisible by a lingering mask that is too
      sparse to produce lower image-level interference. Recent studies suggested the
      importance of an updating process in a higher object-level representation, which
      should rely on the processing of visual motion, in this masking. Repetitive
      transcranial magnetic stimulation (rTMS) was used to investigate whether
      functional suppression of motion processing would selectively reduce substitution
      masking. rTMS-induced transient functional disruption of cortical area V5/MT+,
      which is important for motion analysis, or V1, which is reciprocally connected
      with V5/MT+, produced recovery from masking, whereas sham stimulation did not.
      Furthermore, masking remained undiminished following rTMS over the region 2 cm
      posterior to V5/MT+, ruling out nonspecific effects of real stimulation and
      confirming regional specificity of the rTMS effect. The results suggest that
      object continuity via the normal function of the visual motion processing system
      might in part contribute to this masking. The relation of these findings to the
      reentrant processing view of object substitution masking and other visual
      phenomena is discussed.

PMID- 18085960
TI  - Psychological characteristics of people with Parkinson's disease who prematurely
      drop out of professionally led Internet chat support groups.
AB  - Researchers of Internet health interventions have begun to address the problems
      of high attrition rates. Attrition has been a problem for psychosocial
      interventions for nearly 50 years. It is ubiquitous no matter what the type of
      intervention or the modality of delivery. Consistent are the repeated findings
      that demographic characteristics are the most robust variables. We tested the
      hypothesis that the greater the fear and apprehension experienced in
      professionally led Internet support groups, the more likely the participants
      would not complete the 25-week intervention. The sample consisted of 66 people
      with Parkinson's disease; each participant was assigned to one of six chat
      groups. To assess psychological states, we used PCAD, a text analysis program
      analyzing each person's postings during each chat room session. There was a
      statistically significant difference between those who terminated the group early
      and those who completed the intervention on the Anxiety-Fear dimension, F=2.35,
      (6,63), p=0.03. People who dropped out demonstrated higher death and shame
      anxiety. A number of possible designs for online groups that may reduce premature
      attrition are discussed.

PMID- 18085961
TI  - The effects of Web site structure: the role of personal difference.
AB  - This study examined the effects of Web site structures in terms of advertising
      effectiveness- memory, attitude, and behavioral intentions. The primary research
      question for this study is, What type of Web site (Web ad) structure is most
      effective? In the pilot study, we tested the difference between two Web site
      structures, linear and interactive, in terms of traditional advertising
      effectiveness. Results from the pilot study did not support our research
      expectations. However, differences in terms of memory were noted between the two
      structures. After re-creating the Web site based on subjects' comments, in the
      final experiment, we examined the differences between the two structures and the
      moderating role of personality difference on the effects of Web site structure.
      The results confirm that participants' attitude, memory, and behavioral
      intentions were affected differently by the different Web site structures.
      However, some research hypotheses were not supported by the current data.

PMID- 18085962
TI  - Enhanced avatar design using cognitive map-based simulation.
AB  - With the advent of the Internet era and the maturation of electronic commerce,
      strategic avatar design has become an important way of keeping up with market
      changes and customer tastes. In this study, we propose a new approach to an
      adaptive avatar design that uses cognitive map (CM) as a what-if simulation
      vehicle. The main virtue of the new design is its ability to change specific
      avatar design features with objective consideration of the subsequent effects
      upon other design features, thereby enhancing user satisfaction. Statistical
      analyses of focus group interview results with a group of experts majoring in
      avatars and CM showed that our proposed approach could be used to effectively
      analyze avatar design in an adaptive and practical manner when the market
      situation is changing.

PMID- 18085963
TI  - Internet use and its relation with the psychosocial situation for a sample of
      university students.
AB  - This study was carried out to determine the general characteristics of Internet
      use among university students in Turkey and to examine the relation between the
      Internet use and the psychosocial conditions of the students. Among the 730
      university students who participated, the average age was 20.84 (SD=1.95), and
      the majority were females. The average Internet use period of the students was
      detected as 2.80 (SD=1.33) years for females and 3.59 (SD=1.60) years for males.
      The average score of the Online Cognition Scale (OCS) used for determining
      problematic use was 84.64 (SD=33.50): for females, 77.99 (SD=30.70); for males,
      92.16 (SD=34.96). Students of social sciences scored highest on the OCS. It was
      determined that as the OSC score increased, students' performance of Internet
      activities such as general information searches and academic research decreased
      and that performance of interactive and entertainment Internet activities such as
      chat, financial transactions, game playing, sex, downloading programs, and
      listening to MP3s increased. While a positive correlation was found between
      problematic use and loneliness and depression, a negative correlation was found
      between problematic use and perceived social support.

PMID- 18085964
TI  - Dimensions of online behavior: toward a user typology.
AB  - Online behavior refers to organized (e.g., search) and unorganized (e.g., browse)
      interactions with both human (e.g., chat) and nonhuman (e.g., database) elements
      in online environments. The salient features of online behavior are
      conceptualized as sociability (human connection motives), utility (efficiency
      orientation), and reciprocity (cognitive stimulation and active involvement).
      Recently published factor analytic studies support the validity of these three
      dimensions of online behavior. The proposed Brief Test of Online Behavior (BTOB)
      contains five rating scale items that determine user position on each dimension
      of online behavior (i.e., 15 items in total). A typology of online behavior
      emerges as BTOB scores position users in the three-dimensional space created by
      the intersection of sociability, utility, and reciprocity. Subsequent research
      may validate the proposed dimensions of online behavior, establish practical
      applications of the BTOB, and connect type of user with cognitive, social, and
      emotional outcomes. For example, users who score high on sociability and
      reciprocity but low on utility may learn best in interactive and stimulating
      online environments, which necessarily include self-regulating software.

PMID- 18085965
TI  - Using presence to improve a virtual training environment.
AB  - In the rail industry, drivers must be trained to operate complex heavy machinery
      while responding appropriately to rapidly unfolding events in environments that
      are expensive and often dangerous to replicate in the real world. Virtual
      training environments (VTEs) can deliver stress exposure training to improve the
      decision-making skills of train drivers. Higher levels of recallable knowledge in
      the real world have been linked directly to the degree to which trainees have
      been engrossed in their VTE, an experience often measured through the concept of
      "presence." This paper reports on the use of presence to guide improvements to a
      VTE developed to deliver driver training in degraded track conditions. Two
      surveys were used to collect data on train drivers' introspective feedback on the
      level of presence created by the virtual rail environment and the simulator's
      effectiveness in generating immersion across a range of presence causal factors.
      Results indicate that using presence to investigate VTEs has practical
      significance. Outcomes provide direct information on where future improvements
      and modifications to the VTE can be made.

PMID- 18085966
TI  - Use of the computer and Internet among Italian families: first national study.
AB  - Although home Internet access has continued to increase, little is known about
      actual usage patterns in homes. This nationally representative study of over
      4,700 Italian households with children measured computer and Internet use of each
      family member across 3 months. Data on actual computer and Internet usage were
      collected by Nielsen//NetRatings service and provide national baseline
      information on several variables for several age groups separately, including
      children, adolescents, and adult men and women. National averages are shown for
      the average amount of time spent using computers and on the Web, the percentage
      of each age group online, and the types of Web sites viewed. Overall, about one
      third of children ages 2 to 11, three-fourths of adolescents and adult women, and
      over four-fifths of adult men access the Internet each month. Children spend an
      average of 22 hours/month on the computer, with a jump to 87 hours/month for
      adolescents. Adult women spend less time (about 60 hours/month), and adult men
      spend more (over 100). The types of Web sites visited are reported, including the
      top five for each age group. In general, search engines and Web portals are the
      top sites visited, regardless of age group. These data provide a baseline for
      comparisons across time and cultures.

PMID- 18085967
TI  - A study of Internet addiction through the lens of the interpersonal theory.
AB  - Previous studies have presented conflicting claims regarding reasons that people
      become addicted to the Internet. In this study, we attempted to identify
      predictors of Internet addiction based on Sullivan's interpersonal theory and
      Internet addiction literature. In our research model, it is hypothesized that
      good parent-child relationship positively correlates with good interpersonal
      relationships, which in turn are hypothesized to correlate with undesirable
      social anxiety. In addition, both parent-child and interpersonal relationships
      are hypothesized to negatively correlate with Internet addiction, whereas the
      level of social anxiety is hypothesized to positively correlate with Internet
      addiction. The results of this study confirm the research model hypotheses,
      indicating that the quality of parent-child relationship is indeed positively
      correlated to the quality of our participants' interpersonal relationships and
      that frustrating interpersonal relationships may raise the level of social
      anxiety. In addition, interpersonal relationships, the parent-child relationship,
      and social anxiety all influence Internet addiction, as predicted by the model.
      Finally, the more social anxiety and discontent with their peer interactions the
      participants experienced, the more addicted they were to the Internet.

PMID- 18085968
TI  - Chinese Internet addiction inventory: developing a measure of problematic
      Internet use for Chinese college students.
AB  - The current study developed a psychometrically sound multidimensional measure of
      Internet addiction: the Chinese Internet Addiction Inventory (CIAI). Data were
      collected from 1,029 Chinese undergraduate students from 14 universities and
      colleges. The initial sample was split randomly into two samples (N1=516;
      N2=513). An exploratory factor analysis (EFA) and a confirmatory factor analysis
      (CFA) were conducted on the two samples respectively. Findings from the EFA
      suggest that this measure assesses three dimensions of Internet addiction:
      conflicts, mood modification, and dependence. Items in each dimension showed high
      internal consistency and acceptable test-retest reliability. Findings from the
      CFA further confirmed the three-factor measurement structure of CIAI. Test of
      criterion-related validity also showed good abilities for all three CIAI
      subscales to discriminate between an Internet addictive group and non-Internet
      addictive group. The theoretical and clinical implications of CIAI and its
      limitations are discussed.

PMID- 18085969
TI  - A study of the perceived recognition affecting the adoption of innovation with
      respect to the online game in Taiwan.
AB  - The potential of online games to become a major global business and the existence
      of limited related references led to the current study. In this study, Rogers's
      diffusion of innovation (DOI) theory is applied to investigate the principles for
      the adoption of online games in Taiwan. The findings suggest that relative
      advantages and compatibility both have a significant effect on the adoption of
      online games for purposes of amusement, with the former being more important for
      early gamers and the latter being regarded as more critical for later gamers. In
      addition, complexity is found to impede online game diffusion and is regarded as
      the most important facilitator.

PMID- 18085970
TI  - Measuring online learning systems success: applying the updated DeLone and McLean
      model.
AB  - Based on a survey of 232 undergraduate students, this study used the updated
      DeLone and McLean information systems success model to examine the determinants
      for successful use of online learning systems (OLS). The results provided an
      expanded understanding of the factors that measure OLS success. The results also
      showed that system quality, information quality, and service quality had a
      significant effect on actual OLS use through user satisfaction and behavioral
      intention to use OLS.

PMID- 18085971
TI  - The use of health technology and information: e-learning technological approach.
AB  - The Internet is becoming the preferred place for finding information. Millions of
      people go online in search of health and medical information. Likewise, health
      care professionals must be able to retrieve and manage information in an
      efficient, effective manner. The development of health technology and informatics
      (HTI) has been rapid, yet little is known about the knowledge and attitudes of
      nursing students with regard to using HTI. Therefore, the objective of the
      present study was to explore nursing students' knowledge of and attitudes toward
      using HTI and to use an e-learning workshop to enhance the effective use of HTI.
      In Phase I, 115 first-year full-time nursing students were invited to complete a
      13-item questionnaire regarding knowledge of and attitudes toward computer and
      Internet use, knowledge of HTI, and attitudes toward the future development of
      HTI. Participants perceived themselves to be knowledgeable in computer and
      Internet use, while knowledge of HTI was perceived to be low and attitudes toward
      the future development of HTI were generally positive. Phase II was an e-learning
      HTI workshop; topics included an introduction to HTI, examples of HTI in use, and
      the application and implementation of various HTI projects. There were 30
      participants in the E-learning workshop, and their feedback was positive. Nurses
      and all health care professionals must be prepared to participate in the
      development of health technology and informatics. Teaching and learning
      activities should be geared toward mastery of HTI in the nursing education
      curriculum in order to enhance health care quality and safety.

PMID- 18085972
TI  - Developing a sense of virtual community measure.
AB  - Sense of virtual community is an important feature of virtual communities. This
      study develops a sense of virtual community (SOVC) measure, building off the
      strengths of a widely used measure of sense of community (SOC) for face-to-face
      communities. Although there is overlap between the senses of community for face
      to-face and virtual communities, there are significant differences. The new SOVC
      measure is compared to the SOC measure on 265 members of seven online groups,
      explaining at least 7% more of the variance from exchanging support and member
      identification. This study represents an important step in developing a valid
      measure of SOCV.

PMID- 18085973
TI  - Computer-mediated communication and interpersonal attraction: an experimental
      test of two explanatory hypotheses.
AB  - The aims of this study were (a) to investigate the influence of computer-mediated
      communication (CMC) on interpersonal attraction and (b) to examine two underlying
      processes in the CMC-interpersonal attraction relationship. We identified two
      variables that may mediate the influence of CMC on interpersonal attraction: self
      disclosure and direct questioning. Focusing on these potential mediating
      variables, we tested two explanatory hypotheses: the CMC-induced direct
      questioning hypothesis and the CMC-induced self-disclosure hypothesis. Eighty-one
      cross-sex dyads were randomly assigned to one of three experimental conditions:
      text-only CMC, visual CMC, and face-to-face communication. We did not find a
      direct effect of CMC on interpersonal attraction. However, we did find two
      positive indirect effects of text-only CMC on interpersonal attraction: text-only
      CMC stimulated both self-disclosure and direct questioning, both of which in turn
      enhanced interpersonal attraction. Results are discussed in light of uncertainty
      reduction theory and CMC theories.

PMID- 18085974
TI  - How to know and choose online games: differences between current and potential
      players.
AB  - This study investigated how different adolescent players acquire game information
      and the criteria they use in choosing online games and found that (1) current
      players generally use comprehensive information sources more than potential
      players do; (2) current players rely on free trials and smooth display of motion
      graphics as choice criteria more than potential players do; (3) potential players
      rely on the look of advertisements more than current players do; (4) both current
      and potential players most likely use word-of-mouth and gaming programs on TV as
      information sources; and (5) endorser attractiveness is ranked the least
      important among six choice criteria by both current and potential players.

PMID- 18085975
TI  - Development of a scale to measure problem use of short message service: the SMS
      Problem Use Diagnostic Questionnaire.
AB  - This exploratory study examines a subset of mobile phone use, the compulsive use
      of short message service (SMS) text messaging. A measure of SMS use, the SMS
      Problem Use Diagnostic Questionnaire (SMS-PUDQ), was developed and found to
      possess acceptable reliability and validity when compared to other measures such
      as self-reports of time spent using SMS and scores on a survey of problem mobile
      phone use. Implications for the field of addiction research, technological and
      behavioral addictions in particular, are discussed, and directions for future
      research are suggested.

PMID- 18085976
TI  - Effectance and control as determinants of video game enjoyment.
AB  - This article explores video game enjoyment originated by games' key
      characteristic, interactivity. An online experiment (N=500) tested experiences of
      effectance (perceived influence on the game world) and of being in control as
      mechanisms that link interactivity to enjoyment. A video game was manipulated to
      either allow normal play, reduce perceived effectance, or reduce perceived
      control. Enjoyment ratings suggest that effectance is an important factor in
      video game enjoyment but that the relationship between control of the game
      situation and enjoyment is more complex.

PMID- 18085977
TI  - Who visits online dating sites? Exploring some characteristics of online daters.
AB  - Although online dating has become an important strategy in finding a romantic
      partner, academic research into the antecedents of online dating is still scarce.
      The aim of this study was to investigate (a) the demographic predictors of online
      dating and (b) the validity of two opposite hypotheses that explain users'
      tendency to use the Internet for online dating: the social compensation and the
      rich-get-richer hypotheses. We presented 367 single Dutch Internet users between
      18 and 60 years old with an online questionnaire. We found that online dating was
      unrelated to income and educational level. Respondents between 30 and 50 years
      old were the most active online daters. In support of the rich-get-richer
      hypothesis, people low in dating anxiety were more active online daters than
      people high in dating anxiety.

PMID- 18085978
TI  - Cultural illiteracy and the Internet.
AB  - The Internet has created different expectations regarding its possibilities as a
      tool for including groups that have heretofore been excluded from the modern
      world. But mere access to information does not necessarily imply correct and
      effective use of it. Despite the great increase in Internet access in previously
      excluded areas, expectations of inclusion have not been fulfilled. Research
      suggests that the effectiveness of Internet use varies among cultures, but all
      such studies analyze countries as a whole with no further breakdown. Yet it is
      known that within a given country there co-exist subcultures that differ both in
      language and social context. This paper presents a study that shows the
      correlation between different social subcultures and their Internet knowledge.

PMID- 18085982
TI  - A study on neural learning on manifold foliations: the case of the Lie group
      SU(3).
AB  - Learning on differential manifolds may involve the optimization of a function of
      many parameters. In this letter, we deal with Riemannian-gradient-based
      optimization on a Lie group, namely, the group of unitary unimodular matrices
      SU(3). In this special case, subalgebras of the associated Lie algebra su(3) may
      be individuated by computing pair-wise Gell-Mann matrices commutators.
      Subalgebras generate subgroups of a Lie group, as well as manifold foliation. We
      show that the Riemannian gradient may be projected over tangent structures to
      foliation, giving rise to foliation gradients. Exponentiations of foliation
      gradients may be computed in closed forms, which closely resemble Rodriguez forms
      for the special orthogonal group SO(3). We thus compare optimization by
      Riemannian gradient and foliation gradients.

PMID- 18085983
TI  - Constrained subspace ICA based on mutual information optimization directly.
AB  - We introduce a new approach to constrained independent component analysis (ICA)
      by formulating the original, unconstrained ICA problem as well as the constraints
      in mutual information terms directly. As an estimate of mutual information, a
      robust version of the Edgeworth expansion is used, on which gradient descent is
      performed. As an application, we consider the extraction of both the mother and
      the fetal antepartum electrocardiograms (ECG) from multielectrode cutaneous
      recordings on the mother's thorax and abdomen.

PMID- 18085984
TI  - Dynamical constraints on using precise spike timing to compute in recurrent
      cortical networks.
AB  - Several recent models have proposed the use of precise timing of spikes for
      cortical computation. Such models rely on growing experimental evidence that
      neurons in the thalamus as well as many primary sensory cortical areas respond to
      stimuli with remarkable temporal precision. Models of computation based on spike
      timing, where the output of the network is a function not only of the input but
      also of an independently initializable internal state of the network, must,
      however, satisfy a critical constraint: the dynamics of the network should not be
      sensitive to initial conditions. We have previously developed an abstract
      dynamical system for networks of spiking neurons that has allowed us to identify
      the criterion for the stationary dynamics of a network to be sensitive to initial
      conditions. Guided by this criterion, we analyzed the dynamics of several
      recurrent cortical architectures, including one from the orientation selectivity
      literature. Based on the results, we conclude that under conditions of sustained,
      Poisson-like, weakly correlated, low to moderate levels of internal activity as
      found in the cortex, it is unlikely that recurrent cortical networks can robustly
      generate precise spike trajectories, that is, spatiotemporal patterns of spikes
      precise to the millisecond timescale.

PMID- 18085985
TI  - Phase precession through synaptic facilitation.
AB  - Phase precession is a relational code that is thought to be important for
      episodic-like memory, for instance, the learning of a sequence of places. In the
      hippocampus, places are encoded through bursting activity of so-called place
      cells. The spikes in such a burst exhibit a precession of their firing phases
      relative to field potential theta oscillations (4-12 Hz); the theta phase of
      action potentials in successive theta cycles progressively decreases toward
      earlier phases. The mechanisms underlying the generation of phase precession are,
      however, unknown. In this letter, we show through mathematical analysis and
      numerical simulations that synaptic facilitation in combination with membrane
      potential oscillations of a neuron gives rise to phase precession. This
      biologically plausible model reproduces experimentally observed features of phase
      precession, such as (1) the progressive decrease of spike phases, (2) the
      nonlinear and often also bimodal relation between spike phases and the animal's
      place, (3) the range of phase precession being smaller than one theta cycle, and
      (4) the dependence of phase jitter on the animal's location within the place
      field. The model suggests that the peculiar features of the hippocampal mossy
      fiber synapse, such as its large efficacy, long-lasting and strong facilitation,
      and its phase-locked activation, are essential for phase precession in the CA3
      region of the hippocampus.

PMID- 18085986
TI  - Dynamics and computation of continuous attractors.
AB  - Continuous attractor is a promising model for describing the encoding of
      continuous stimuli in neural systems. In a continuous attractor, the stationary
      states of the neural system form a continuous parameter space, on which the
      system is neutrally stable. This property enables the neutral system to track
      time-varying stimuli smoothly, but it also degrades the accuracy of information
      retrieval, since these stationary states are easily disturbed by external noise.
      In this work, based on a simple model, we systematically investigate the dynamics
      and the computational properties of continuous attractors. In order to analyze
      the dynamics of a large-size network, which is otherwise extremely complicated,
      we develop a strategy to reduce its dimensionality by utilizing the fact that a
      continuous attractor can eliminate the noise components perpendicular to the
      attractor space very quickly. We therefore project the network dynamics onto the
      tangent of the attractor space and simplify it successfully as a one-dimensional
      Ornstein-Uhlenbeck process. Based on this simplified model, we investigate (1)
      the decoding error of a continuous attractor under the driving of external noisy
      inputs, (2) the tracking speed of a continuous attractor when external stimulus
      experiences abrupt changes, (3) the neural correlation structure associated with
      the specific dynamics of a continuous attractor, and (4) the consequence of
      asymmetric neural correlation on statistical population decoding. The potential
      implications of these results on our understanding of neural information
      processing are also discussed.

PMID- 18085987
TI  - Sequential fixed-point ICA based on mutual information minimization.
AB  - A new gradient technique is introduced for linear independent component analysis
      (ICA) based on the Edgeworth expansion of mutual information, for which the
      algorithm operates sequentially using fixed-point iterations. In order to address
      the adverse effect of outliers, a robust version of the Edgeworth expansion is
      adopted, in terms of robust cumulants, and robust derivatives of the Hermite
      polynomials are used. Also, a new constrained version of ICA is introduced, based
      on goal programming of mutual information objectives, which is applied to the
      extraction of the antepartum fetal electrocardiogram from multielectrode
      cutaneous recordings on the mother's thorax and abdomen.

PMID- 18085988
TI  - Predictive coding and the slowness principle: an information-theoretic approach.
AB  - Understanding the guiding principles of sensory coding strategies is a main goal
      in computational neuroscience. Among others, the principles of predictive coding
      and slowness appear to capture aspects of sensory processing. Predictive coding
      postulates that sensory systems are adapted to the structure of their input
      signals such that information about future inputs is encoded. Slow feature
      analysis (SFA) is a method for extracting slowly varying components from quickly
      varying input signals, thereby learning temporally invariant features. Here, we
      use the information bottleneck method to state an information-theoretic objective
      function for temporally local predictive coding. We then show that the linear
      case of SFA can be interpreted as a variant of predictive coding that maximizes
      the mutual information between the current output of the system and the input
      signal in the next time step. This demonstrates that the slowness principle and
      predictive coding are intimately related.

PMID- 18085989
TI  - Almost periodic dynamics of a class of delayed neural networks with discontinuous
      activations.
AB  - We use the concept of the Filippov solution to study the dynamics of a class of
      delayed dynamical systems with discontinuous right-hand side, which contains the
      widely studied delayed neural network models with almost periodic self
      inhibitions, interconnection weights, and external inputs. We prove that diagonal
      dominant conditions can guarantee the existence and uniqueness of an almost
      periodic solution, as well as its global exponential stability. As special cases,
      we derive a series of results on the dynamics of delayed dynamical systems with
      discontinuous activations and periodic coefficients or constant coefficients,
      respectively. From the proof of the existence and uniqueness of the solution, we
      prove that the solution of a delayed dynamical system with high-slope activations
      approximates to the Filippov solution of the dynamical system with discontinuous
      activations.

PMID- 18085990
TI  - Spike train decoding without spike sorting.
AB  - We propose a novel paradigm for spike train decoding, which avoids entirely spike
      sorting based on waveform measurements. This paradigm directly uses the spike
      train collected at recording electrodes from thresholding the bandpassed voltage
      signal. Our approach is a paradigm, not an algorithm, since it can be used with
      any of the current decoding algorithms, such as population vector or likelihood
      based algorithms. Based on analytical results and an extensive simulation study,
      we show that our paradigm is comparable to, and sometimes more efficient than,
      the traditional approach based on well-isolated neurons and that it remains
      efficient even when all electrodes are severely corrupted by noise, a situation
      that would render spike sorting particularly difficult. Our paradigm will also
      save time and computational effort, both of which are crucially important for
      successful operation of real-time brain-machine interfaces. Indeed, in place of
      the lengthy spike-sorting task of the traditional approach, it involves an exact
      expectation EM algorithm that is fast enough that it could also be left to run
      during decoding to capture potential slow changes in the states of the neurons.

PMID- 18085991
TI  - The diffusion decision model: theory and data for two-choice decision tasks.
AB  - The diffusion decision model allows detailed explanations of behavior in two
      choice discrimination tasks. In this article, the model is reviewed to show how
      it translates behavioral data-accuracy, mean response times, and response time
      distributions-into components of cognitive processing. Three experiments are used
      to illustrate experimental manipulations of three components: stimulus difficulty
      affects the quality of information on which a decision is based; instructions
      emphasizing either speed or accuracy affect the criterial amounts of information
      that a subject requires before initiating a response; and the relative
      proportions of the two stimuli affect biases in drift rate and starting point.
      The experiments also illustrate the strong constraints that ensure the model is
      empirically testable and potentially falsifiable. The broad range of applications
      of the model is also reviewed, including research in the domains of aging and
      neurophysiology.

PMID- 18085992
TI  - A homomorphic neural network for modeling and prediction.
AB  - A homomorphic feedforward network (HFFN) for nonlinear adaptive filtering is
      introduced. This is achieved by a two-layer feedforward architecture with an
      exponential hidden layer and logarithmic preprocessing step. This way, the
      overall input-output relationship can be seen as a generalized Volterra model, or
      as a bank of homomorphic filters. Gradient-based learning for this architecture
      is introduced, together with some practical issues related to the choice of
      optimal learning parameters and weight initialization. The performance and
      convergence speed are verified by analysis and extensive simulations. For rigor,
      the simulations are conducted on artificial and real-life data, and the
      performances are compared against those obtained by a sigmoidal feedforward
      network (FFN) with identical topology. The proposed HFFN proved to be a viable
      alternative to FFNs, especially in the critical case of online learning on small-
      and medium-scale data sets.

PMID- 18085993
TI  - Pharmacogenomics of microRNA: a miRSNP towards individualized therapy.

PMID- 18085994
TI  - Genomic landscapes of cancers: prospects for targeted therapies.

PMID- 18085996
TI  - Microarray technology--advances, applications, future prospects.

PMID- 18085997
TI  - Pyrosequencing of polymorphisms in the COX-2 gene (PTGS2) with reported clinical
      relevance.
AB  - INTRODUCTION: Genetic variants in the prostaglandin-endoperoxide synthase 2
      (PTGS2) gene, which codes for COX-2, have been identified to modulate the
      response to COX-2-inhibiting drugs and to be possible risk factors for the
      incidence or prognosis of cardiovascular or neoplastic diseases, Alzheimer's
      disease, multiple sclerosis, asthma or osteoarthritis. Clinical evidence thus
      suggests a clinical importance of COX-2 genetics reaching from disease risk or
      prognostics up to a personalized therapy with COX-2 inhibitors. The aim of this
      study was to develop rapid and reliable screening assays for PTGS2 mutations with
      reported clinical consequences. METHODS: SNPs (dbSNP-IDs rs689465, rs689466,
      rs3918304, rs20415, rs20417, rs5270, rs2745557, rs5277, rs2066826, rs4648276,
      rs5273, rs5275, rs4648298, rs689469) and a nucleotide-deletion variant (rs20431)
      were chosen according to reported functional associations. For this selection of
      variants spanning the whole PTGS2 gene range, Pyrosequencing assays were
      established in DNA from 350 healthy unrelated Caucasians. RESULTS: In all 350 DNA
      samples, the 15 PTGS2 polymorphisms were identified correctly as verified by
      control samples obtained by conventional sequencing. In silico haplotype analysis
      based on ten SNPs of greater than 1% observed frequencies identified two
      haploblocks with a linkage disequilibrium of D' = 0.59. Approximately 50% of the
      reconstructed haplotypes consisted of non-mutated alleles. CONCLUSION: The
      presently developed Pyrosequencing assays allow for quick and reliable detection
      of PTGS2 genotypes and may promote further research toward personalized
      approaches to pathophysiological conditions involving COX-2.

PMID- 18085998
TI  - Investigation into the multidimensional genetic basis of drug-induced Stevens
      Johnson syndrome and toxic epidermal necrolysis.
AB  - OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are rare severe blistering skin diseases, which are mainly caused by drugs. The
      two idiosyncratic conditions are distinguished on the basis of the degree of
      blistering, possibly representing diseases at different ends of the same
      spectrum. A genetic predisposition has been postulated. METHOD: We have
      retrospectively identified a heterogeneous group of patients with SJS and TEN (n
      = 73 cases, 141 matched controls) induced by a number of marketed drugs and
      evaluated effector candidate genetic predisposition. We have used a multivariate
      genetic analysis method for the first time to handle the heterogeneity of
      clinical presentation, drug etiology, ethnicity and gender in these adverse
      events. RESULTS: Our results show that predisposition varied according to
      ethnicity. There was a correlation for SJS with HLA-B*44, DRB1*07 and with the
      MHC ancestral 57.1 haplotype (and its constituents) in subjects who self-reported
      as Caucasians, which did not differ with gender. The HLA-DRB and -DRQ genetic
      predisposition to SJS seemed to be distinct from that of TEN, but further work is
      needed for both conditions to identify the causal variants. No conclusion
      concerning correlations with different drugs could be made because of small
      numbers in each drug group. CONCLUSION: This study stresses the importance of
      accurate clinical phenotyping, exemplifies a novel analysis method to dissect
      complicated samples and calls for collaborative prospective studies.

PMID- 18085999
TI  - Determination of ERCC2 Lys751Gln and GSTP1 Ile105Val gene polymorphisms in
      colorectal cancer patients: relationships with treatment outcome.
AB  - INTRODUCTION: Glutathione S-transferase P1 (GSTP1) and excision-repair cross
      complementing repair deficiency group 2 protein (ERCC2 or XPD) may modulate the
      activity of platinum derivatives. The SNPs, Ile105Val for GSTP1 and Lys751Gln for
      ERCC2, may affect the efficiency of oxaliplatin in patients treated with an
      oxaliplatin-based regimen for metastatic colorectal carcinoma. PATIENTS &
      METHODS: A total of 107 patients treated with first-line chemotherapy, 59 with an
      oxaliplatin-based regimen and 48 with an irinotecan-based regimen, were included
      retrospectively. GSTP1 and ERCC2 genotypes were identified on DNA samples
      extracted from paraffin blocks containing either normal tissue (nodes) or tumor
      tissue. We analyzed treatment response, event-free and overall survival. RESULTS:
      GSTP1 genotype distribution was Ile/Ile 58%, Ile/Val 35% and Val/Val 7%. ERCC2
      genotype distribution was Lys/Lys 49%, Lys/Gln 44%, Gln/Gln 7%. Event-free and
      overall survivals were not significantly different as a function of the GSTP1
      genotype, whatever the treatment received. Event-free survival was significantly
      different as a function of the ERCC2 genotype only in patients receiving
      oxaliplatin: patients having at least one variant allele had a shorter median
      event-free survival (6 months) than those having no variant allele (11.6 months,
      p = 0.008). This difference was maintained for median overall survival (15.6 vs
      25.3 months, p = 0.016). Using univariate analysis, ERCC2 genotype,
      hemoglobinemia and carbohydrate antigen 19.9 plasma levels were significantly
      related to overall and event-free survival in patients receiving oxaliplatin.
      CONCLUSION: The ERCC2 genotype appears as an important predictive factor of the
      survival of patients treated with oxaliplatin in first-line therapy for
      metastatic colorectal cancer.

PMID- 18086000
TI  - Serum lactate dehydrogenase levels and glycolysis significantly correlate with
      tumor VEGFA and VEGFR expression in metastatic CRC patients.
AB  - OBJECTIVES: In an attempt to elucidate the relationship between biomarkers of
      tumor hypoxia, glycolysis and angiogenesis, we tested the hypothesis that
      intratumoral gene expression of the hypoxia response (hypoxia inducible factor
      [HIF1 alpha and 2 alpha]), glycolysis (lactate dehydrogenase A [LDHA]), glucose
      metabolism (glucose transporter-1 [Glut-1]) and genes involved in angiogenesis
      (i.e., VEGFA, VEGFR1-3, and neuropilin [NRP]1) are upregulated in metastatic
      colorectal cancer (mCRC) patients with high serum lactate dehydrogenase (LDH).
      PATIENTS AND METHODS: 78 formalin-fixed, paraffin-embedded (FFPE) tumor samples
      were collected from 36 patients with mCRC. Tumor gene expression was correlated
      with serum LDH levels from the same group of patients. FFPE tissues were
      dissected using laser-captured microdissection and analyzed for gene expression
      using a quantitative real-time RT-PCR method. RESULTS: Intratumoral gene
      expression of VEGFA and VEGFR1 showed a statistically significant correlation
      with serum LDH levels (p = 0.006, r = 0.45 and p = 0.004, r = 0.50,
      respectively). Intratumoral expression of LDHA gene showed a significant
      correlation with Glut-1, VEGF, HIF1 alpha, HIF2 alpha and VEGFR1 (p = 0.007, r =
      0.44; p < 0.001, r = 0.57; p = 0.013, r = 0.41; p = 0.044, r = 0.34; p = 0.026, r
      = 0.40). Serum LDH levels also correlated with microvessel density analyzed by
      immunohistochemical analysis. CONCLUSION: The results demonstrated a significant
      correlation between the intratumoral gene expression of LDHA, HIF1 alpha, HIF2
      alpha, Glut-1, NRP1, VEGFA and VEGFR1. Patients with high serum LDH have
      increased intratumoral gene expression of VEGFA and VEGFR1. The results also
      support the hypothesis that serum LDH levels may serve as a surrogate marker for
      activation of the HIF-related genes in the tumor.

PMID- 18086001
TI  - The association between polymorphisms in RLIP76 and drug response in epilepsy.
AB  - INTRODUCTION: Approximately 30% of patients with epilepsy are resistant to
      treatment with anti-epileptic drugs (AEDs). The ABC drug transporter proteins are
      hypothesized to mediate drug resistance in epilepsy. More recently, a non-ABC
      putative transporter, RLIP76, has also been proposed to be involved in the
      mechanism of pharmacoresistance. One previous association study of six
      polymorphisms in RLIP76 failed to find any association with drug resistance in a
      retrospective cohort of epilepsy patients. We aimed to look for an association
      with outcomes reflecting drug response in a larger prospective cohort, with gene
      wide coverage. PATIENTS AND METHODS: We investigated the role of common
      polymorphisms in RLIP76 in epilepsy pharmacoresistance by genotyping 23 common
      RLIP76 polymorphisms in a prospective cohort of 503 epilepsy patients, from the
      standard and new anti-epileptic drugs (SANAD) prospective study of new and old
      AEDs. A total of 13 of these were tested for association with four outcomes
      reflecting response to drugs: time to first seizure, time to 12-month remission,
      time to withdrawal due to inadequate seizure control, and time to withdrawal due
      to unacceptable adverse drug events. RESULTS: No significant associations,
      allowing for multiple testing, were found in the whole cohort. There was also no
      effect in a subgroup of patients on carbamazepine, which is thought to be a
      RLIP76 substrate, although two polymorphisms were associated with time to first
      seizure (p = 0.007). DISCUSSION: We failed to demonstrate any association between
      RLIP76 polymorphisms and four different measures of drug response in the larger
      cohort, but a subgroup analysis of patients receiving carbamazepine suggested an
      association that should be investigated further. CONCLUSIONS: Our data suggest
      that common variants in RLIP76 are unlikely to contribute to epilepsy drug
      response.

PMID- 18086002
TI  - Endothelial nitric oxide synthase gene: prospects for treatment of heart disease.
AB  - Nitric oxide functions as a signaling molecule with a well-established role in
      vascular homeostasis. It is synthesized from the oxidation of L-arginine by the
      enzyme, endothelial nitric oxide synthase (eNOS). The eNOS gene has a number of
      polymorphic sites, including SNPs, dinucleotide repeats and variable number
      tandem repeat sequences, and the opportunity exists to investigate polymorphic
      functional correlates as well as disease-specific associations, especially in
      cardiovascular disease, including coronary artery disease, and its most severe
      consequence, myocardial infarction. A number of clinical and functional
      correlative studies involving eNOS polymorphisms have been reported and are
      presented. The promise and complexity of pharmacogenetics is illustrated using
      eNOS as an example because of its relationship with cardiovascular biology and
      pathology. In this review, we will discuss the impact of nitric oxide, eNOS,
      genetic regulation, clinical investigation and, ultimately, prospects for
      treatment of heart disease.

PMID- 18086003
TI  - Alzheimer's disease and genetics of inflammation: a pharmacogenomic vision.
AB  - Inflammation plays a key role in Alzheimer disease, and dissecting the genetics
      of inflammation may provide an answer to the possible treatment. The next
      generation therapy is based on a pharmacogenomics that will reconure new
      approaches to a drug used on definite people with specific dosage. The
      translation of pharmacogenomics into clinical practice will allow bold steps to
      be taken toward personalized medicine. In response to tissue injury elicited by
      trauma or infection, the inflammatory response sets in as a complex network of
      molecular and cellular interactions, directed to facilitate a return to
      physiological homeostasis and tissue repair. The role of an individual's genetic
      background and predisposition for the extent of an inflammatory response is
      determined by variability of genes encoding endogenous mediators that constitute
      the pathways of inflammation. Due to its clinical relevance, in this review, the
      view on genetics of inflammation will be illustrated through a description of the
      genetic basis of a specific inflammatory disease, Alzheimer's disease (AD).
      Several studies report a significantly different distribution, in patients and
      controls, of proinflammatory genes, alleles of which are under-represented in
      control subjects and over-represented in patients affected by AD. These studies
      will permit the detection of a risk profile that will potentially allow both the
      early identification of individuals susceptible to disease and the possible
      design or utilization of drug at the right dose for a desired effect - a
      pharmacogenomic approach for this disease.

PMID- 18086004
TI  - Genetics of late-onset Alzheimer's disease: progress and prospect.
AB  - Genetic susceptibility factors for late-onset Alzheimer's disease remain largely
      elusive, with the exception of apolipoprotein E4 (APOE e4) as the only confirmed
      genetic risk factor. Numerous other putative risk markers have been proposed,
      although all suffer inconsistent replication. These results suggest that modest
      effect sizes are likely to be the norm for non-APOE-related factors. This
      unsettling situation has been similar to other complex diseases such as diabetes
      and cardiovascular diseases until very recently, when a spate of new, although
      weak, genetic markers has been convincingly linked to these conditions. If we
      assume that multiple weak factors, together with APOE e4, account for the genetic
      contribution to late-onset Alzheimer's disease risk, it will require the
      concerted efforts of the greater Alzheimer's genetics community to pool existing
      genetic resources and/or data to identify novel genetic risk factors that are
      genuine. Increased confidence in the disease-associated factors will provide the
      foundation to develop better diagnostic and prognostic tests, select new drug
      targets and, perhaps, elucidate pharmacogenetic markers that assist in making the
      best treatment decisions.

PMID- 18086005
TI  - Dynamic computational modeling in the search for better breast cancer drug
      therapy.
AB  - Breast cancer is an excellent disease paradigm for systems biology. At the time
      of writing, a simple PubMed search for 'breast cancer' returns nearly 99,000
      hits, compared with 51,000 or 16,000 for lung and colon cancer respectively, even
      though in terms of mortality lung and colon cancers are responsible for four
      times more deaths per annum in the UK. These figures reflect the effort and money
      invested in breast cancer research. It is because breast cancer research is data
      rich, crowded and competitive (often perceived as a negative for clinical and
      basic scientific researchers) that it is such an appealing area of research for
      systems biologists. For systems biologists, data is currency, and they scavenge
      diverse and multilayered datasets, from biochemical through genomics and
      transcriptomics to proteomics, in order to populate computational models. We
      discuss how dynamic modeling can be used as a tool for predicting responses to
      new and existing drugs, and what needs to be done to make systems biology a
      useful tool in the clinic.

PMID- 18086006
TI  - Regulation of bone turnover by sex steroids in men.
AB  - INTRODUCTION: The mechanism(s) by which sex steroids regulate bone turnover in
      humans are unclear, and recent studies have suggested that follicle-stimulating
      hormone (FSH) may play an important role in regulating bone resorption. MATERIALS
      AND METHODS: Fifty-nine men (median age, 69 yr) underwent suppression of sex
      steroids using a gonadotropin-releasing hormone (GnRH) agonist and aromatase
      blocker and were replaced with testosterone (T; 5 mg/d) and estradiol (E; 37.5
      microg/d). After assessment of bone resorption markers (serum C-terminal
      telopeptide of type I collagen [CTX] and TRACP5b), they were randomized to sex
      steroid deficiency (-T, -E), E alone (-T, +E), T alone (+T, -E), or both (+T, +E)
      and restudied 3 wk later. Bone marrow aspirates were obtained to isolate
      osteoblastic, T, and monocytic cells using magnetic-activated cell sorting.
      RESULTS: Serum CTX and TRACP5b increased significantly (by 71% and 15%, p < 0.01
      and < 0.001, respectively) in the -T, -E group, and these increases occurred
      despite a 60% suppression of serum FSH levels (p < 0.001) caused by the GnRH
      agonist. There were significant E (but not T) effects on preventing increases in
      serum CTx and TRACP levels. There was a nonsignificant trend (p = 0.122) for E to
      suppress RANKL mRNA levels in bone marrow osteoblastic cells. Changes in mRNA
      levels for other cytokines (TNF-alpha, interleukin (IL)-1alpha, IL-1beta, IL-1ra,
      IFN-gamma) in bone marrow cells were not significant. CONCLUSIONS: E has greater
      suppressive effects on bone resorption than T, and increased bone resorption
      after sex steroid deficiency can occur independently of changes in FSH secretion.
      E effects on bone resorption may be mediated by regulation of RANKL production by
      osteoblastic cells, although further studies using more highly purified cells may
      reduce the variability of the mRNA measurements and allow for clearer definition
      of the mediators of sex steroid action in vivo.

PMID- 18086007
TI  - Impact of pregnancy-associated plasma protein-a deletion on the adult murine
      skeleton.
AB  - INTRODUCTION: The metalloproteinase, pregnancy-associated plasma protein-A (PAPP
      A) functions to enhance local insulin-like growth factor (IGF)-I bioavailability
      through cleavage of inhibitory IGF binding proteins. Because IGF-I is an
      important regulator of skeletal growth and remodeling and PAPP-A is highly
      expressed by osteoblastic cells, we hypothesized that, in the absence of PAPP-A,
      bone physiology would be compromised because of a blunting of local IGF-I action
      even in the presence of normal circulating IGF-I levels. MATERIALS AND METHODS:
      pQCT, muCT, histomorphometry, and mechanical strength testing were performed on
      bones from PAPP-A knockout (KO) mice and wildtype (WT) littermates at 2-12 mo of
      age. IGF-I levels and bone formation and resorption markers were determined in
      sera from these animals. RESULTS: Volumetric BMD in PAPP-A KO mice measured by
      pQCT at the femoral midshaft, which is primarily cortical bone, was 10% less than
      WT at 2 mo. This difference was maintained at 4, 6, and 12 mo. Cortical thickness
      at this site was similarly decreased. On the other hand, trabecular bone at the
      distal femur (pQCT) and in the tibia (muCT) showed age-progressive decreases in
      bone volume fraction in PAPP-A KO compared with WT mice. Tibial muCT indicated a
      46% relative decrease in trabecular bone volume/total volume (BV/TV) and a 28%
      relative decrease in trabecular thickness in PAPP-A KO compared with WT mice at 6
      mo. These trabecular deficiencies in PAPP-A KO mice corresponded to a weakening
      of the bone. Serum markers and bone histomorphometry indicated that the primary
      impact of PAPP-A is on skeletal remodeling resulting in a state of low-turnover
      osteopenia in adult PAPP-A KO mice. Circulating IGF-I levels were not altered in
      PAPP-A KO mice. CONCLUSIONS: PAPP-A is a bone growth regulatory factor in vivo
      and, in its absence, mice show skeletal insufficiency in mass, density,
      architecture, and strength. The data suggest a primary role for PAPP-A in
      modulating local IGF bioavailability for trabecular bone remodeling.

PMID- 18086008
TI  - Role of Bcl2 in osteoclastogenesis and PTH anabolic actions in bone.
AB  - INTRODUCTION: B-cell leukemia/lymphoma 2 (Bcl2) is a proto-oncogene best known
      for its ability to suppress cell death. However, the role of Bcl2 in the skeletal
      system is unknown. Bcl2 has been hypothesized to play an important anti-apoptotic
      role in osteoblasts during anabolic actions of PTH. Although rational, this has
      not been validated in vivo; hence, the impact of Bcl2 in bone remains unknown.
      MATERIALS AND METHODS: The bone phenotype of Bcl2 homozygous mutant (Bcl2(-/-))
      mice was analyzed with histomorphometry and muCT. Calvarial osteoblasts were
      isolated and evaluated for their cellular activity. Osteoclastogenesis was
      induced from bone marrow cells using RANKL and macrophage-colony stimulating
      factor (M-CSF), and their differentiation was analyzed. PTH(1-34) (50 microg/kg)
      or vehicle was administered daily to Bcl2(+/+) and Bcl2(-/-) mice (4 days old)
      for 9 days to clarify the influence of Bcl2 ablation on PTH anabolic actions.
      Western blotting and real-time PCR were performed to detect Bcl2 expression in
      calvarial osteoblasts in response to PTH ex vivo. RESULTS: There were reduced
      numbers of osteoclasts in Bcl2(-/-) mice, with a resultant increase in bone mass.
      Bcl2(-/-) bone marrow-derived osteoclasts ex vivo were significantly larger in
      size and short-lived compared with wildtype, suggesting a pro-apoptotic nature of
      Bcl2(-/-) osteoclasts. In contrast, osteoblasts were entirely normal in their
      proliferation, differentiation, and mineralization. Intermittent administration
      of PTH increased bone mass similarly in Bcl2(+/+) and Bcl2(-/-) mice. Finally,
      Western blotting and real-time PCR showed that Bcl2 levels were not induced in
      response to PTH in calvarial osteoblasts. CONCLUSIONS: Bcl2 is critical in
      osteoclasts but not osteoblasts. Osteoclast suppression is at least in part
      responsible for increased bone mass of Bcl2(-/-) mice, and Bcl2 is dispensable in
      PTH anabolic actions during bone growth.

PMID- 18086010
TI  - Growth of hairy-root cultures in various bioreactors for the production of
      secondary metabolites.
AB  - Agrobacterium rhizogenes-mediated hairy-root cultures are a very promising
      alternative to the biotechnological exploitation of plant cell cultures. Their
      characteristic capacity for secondary-metabolite production, inherent genetic
      stability reflected in stable productivity and the possibility of genetic
      manipulation to increase biosynthetic capacity have initiated a considerable
      interest, both as a fundamental research tool and as a source of valuable
      products. One of the most important limitations for the commercial exploitation
      of hairy roots is the development of technologies for large-scale culture. Though
      these roots have been grown in various bioreactors--stirred-tank, bubble-column,
      airlift or submerged, trickle-bed and nutrient mist--the question as to which of
      these alternatives can be successfully and economically scaled-up has yet to be
      definitively answered. This present minireview highlights various perspectives of
      hairy-root cultures, describes a comparative scale-up study and discusses various
      aspects of these cultures when grown in various bioreactors for the production of
      secondary metabolites.

PMID- 18086009
TI  - Enzyme replacement therapy for murine hypophosphatasia.
AB  - INTRODUCTION: Hypophosphatasia (HPP) is the inborn error of metabolism that
      features rickets or osteomalacia caused by loss-of-function mutation(s) within
      the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase
      (TNALP). Consequently, natural substrates for this ectoenzyme accumulate
      extracellulary including inorganic pyrophosphate (PPi), an inhibitor of
      mineralization, and pyridoxal 5'-phosphate (PLP), a co-factor form of vitamin B6.
      Babies with the infantile form of HPP often die with severe rickets and sometimes
      hypercalcemia and vitamin B6-dependent seizures. There is no established medical
      treatment. MATERIALS AND METHODS: Human TNALP was bioengineered with the C
      terminus extended by the Fc region of human IgG for one-step purification and a
      deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10).
      TNALP-null mice (Akp2-/-), an excellent model for infantile HPP, were treated
      from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted
      of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15,
      19, and 15 or 52 days, respectively. We assessed survival and growth rates,
      circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well
      as skeletal and dental manifestations using radiography, microCT, and
      histomorphometry. RESULTS: Akp2-/- mice receiving high-dose sALP-FcD10 grew
      normally and appeared well without skeletal or dental disease or epilepsy. Plasma
      calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We
      found no evidence of significant skeletal or dental disease. CONCLUSIONS: Enzyme
      replacement using a bone-targeted, recombinant form of human TNALP prevents
      infantile HPP in Akp2-/- mice.

PMID- 18086011
TI  - BCG-malaria co-Infection has paradoxical effects on C57BL/6 and A/J mouse
      strains.
AB  - Bacillus Calmette-Guerin (BCG) infection of the spleen is a potent modifier of
      splenic function. Prior to malaria infection, we infected two mouse strains of
      differing susceptibility to Plasmodium chabaudi AS (C57BL/6 and A/J) with this
      mycobacterium. We then evaluated aspects of spleen cell composition, architecture
      and cytokine expression, and correlated these with the outcome. BCG preinfection
      resulted in protection of the A/J mice but paradoxically resulted in mortality of
      the C57BL/6 mice. The latter developed higher parasitaemias that peaked earlier
      than the A/J mice rendered resistant by BCG. BCG infection induced remarkable
      changes to splenic histology examined by H&E staining, but there were no
      consistent differences between mouse strains. C57BL/6 mice had higher absolute
      numbers of all immune cell phenotypes than did A/J mice, and higher macrophage
      and dendritic cell proportions. BCG-induced resistance in A/J mice was associated
      with an increased CD4+ expression of IFN-gamma whilst induced death in C57BL/6
      mice was associated with excessive IFN-gamma expression. A moderate TH1 response
      in the A/J model may have been responsible for the improved survival, and an
      excessive TH1 response in the C57BL/6 model may have contributed to their death.

PMID- 18086012
TI  - Recognition profiles of microsporidian Encephalitozoon cuniculi polar tube
      protein 1 with human immunoglobulin M antibodies.
AB  - Microsporidian Encephalitozoon cuniculi has a unique organelle called a polar
      tube (PT), the extrusion of which is absolutely required to invade a host cell.
      We recently detected anti-E. cuniculi PT immunoglobulin (Ig) M antibodies in sera
      from many healthy individuals. The present one-dimensional (1-D) immunoblot
      analysis predominantly detected a band at 52 kDa in all of the examined human
      sera with anti-PT IgM. The use of mouse monoclonal antibody confirmed that the 52
      kDa band detected in 1-D immunoblots was an antigen derived from the PT, which
      represents a glycoprotein nature. In addition, from changes in the
      immunoreactivity of the 52-kDa band before and after treatment with NaOH, we
      determined that the 24 human serum samples with anti-PT IgM activities could be
      roughly grouped into three types: (i) sera containing antibodies against only a
      saccharic determinant (n=3); (ii) sera containing antibodies against only a
      proteinic determinant (n=11); and (iii) sera showing dual recognition of
      saccharic and proteinic determinants (n=10). Further two-dimensional (2-D)
      immunoblot analysis followed by proteomic analysis confirmed that human sera with
      anti-PT IgM reacted with E. cuniculi polar tube protein 1 (PTP1). Such
      circulating IgM antibodies may be important in the first line of defence against
      E. cuniculi infection.

PMID- 18086013
TI  - Identification of a 55 kDa Haemonchus contortus excretory/secretory glycoprotein
      as a neutrophil inhibitory factor.
AB  - Haemonchus contortus is an economically important gastric parasite infecting
      sheep and goats. The parasite survives the host immune attack by releasing
      protective molecules. In the present study, a 55 kDa secretory glycoprotein
      (gp55) was identified that inhibited host neutrophils as judged by reduced H2O2
      production by these cells. The binding of gp55 to neutrophils was confirmed by
      flow cytometry. This binding was mediated by cellular CD11b/CD18 integrin. The
      glycoprotein gp55 also bound to goat monocytes and lymphocytes and inhibited
      monocyte function. Using light fluorescence microscopy, gp55 was localized at the
      surface of adult worms. The absence of gp55 in the infective L3 larvae and its
      expression in the blood-feeding stage support a role for gp55 in the parasitic
      stage of the organism.

PMID- 18086014
TI  - Intranasal immunization with Naegleria fowleri lysates and Cry1Ac induces
      metaplasia in the olfactory epithelium and increases IgA secretion.
AB  - According to previous reports, intranasal administration of the Cry1Ac protein
      alone or with amoebic lysates increases protection against Naegleria fowleri
      meningoencephalitis in mice, apparently by eliciting IgA responses in the nasal
      mucosa. In the current study, we performed an immunohistochemical analysis of IgA
      in the nasal mucosa of mice immunized intranasally with Cry1Ac, and amoebic
      lysates or a combination of both. The animals were sacrificed 24 h after the last
      immunization or after an intranasal lethal challenge with N. fowleri. Our results
      indicate that all of the intranasal immunizations provoked an increase in areas
      with metaplasia in the olfactory epithelium, allowing for secretion of IgA. As a
      result, IgA antibodies were found interacting with trophozoites in the nasal
      lumen, and there was a marked increase of IgA in the metaplasic epithelium. On
      the other hand in nonimmunized mice trophozoites were observed invading the nasal
      mucosa, which was not the case for immunized mice. Our results suggest that
      intranasal immunization provokes cellular changes in the olfactory epithelium,
      leading to greater protection against N. fowleri that is probably caused by an
      increased secretion of IgA. The increased IgA response induced in the nasal
      mucosa by immunization probably impedes both amoebic adhesion and subsequent
      invasion of the parasite to the nasal epithelium.

PMID- 18086016
TI  - Apoptosis: a potential triggering mechanism of neurological manifestation in
      Plasmodium falciparum malaria.
AB  - Plasmodium falciparum infection can lead to a life threatening disease and the
      pathogenetic mechanisms of severe manifestations are not fully understood. Here,
      we investigated the capacity of P. falciparum-parasitized red blood cells (PRBC)
      from 45 children with clinical malaria to induce endothelial cell (EC) apoptosis.
      In all subjects, PRBC that cytoadhered to ECs could be found albeit to a variable
      degree. By contrast, PRBC that induce EC apoptosis were found only in nine (20%)
      subjects. Interestingly, children with neurological manifestations were
      significantly more likely to harbour apoptogenic strains. There was no
      quantitative relationship between the capacity of these isolates to cytoadhere
      and apoptosis induction. We hypothesize that P. falciparum-encoded molecules
      could be responsible for apoptosis induction and therefore suggest new insights
      in the pathogenesis of P. falciparum malaria. Further investigations are
      currently in progress to determine whether these results can be confirmed and to
      identify putative parasite apoptogenic factors.

PMID- 18086015
TI  - Immunologic activity of schistosomal and bacterial TLR2 ligands in Gabonese
      children.
AB  - Schistosomes carry lipid moieties that interact with the immune system. To
      understand the consequence of interactions in terms of polarizing the cytokine
      profiles, the effect of two Toll-like receptor-2 (TLR2) activating schistosomal
      lipid fractions was studied on whole blood from Gabonese children living in a
      schistosomiasis endemic area. One fraction contained lysophosphatidylserine
      [monoacylglycerophosphoserine (lysoGPSer)] plus diacylphosphatidylserine
      [diacylglycerophosphoserine (GPSer)] while the other contained lysoGPSer and only
      a trace of GPSer. The effect of these schistosomal lipid fractions was compared
      with the known bacterial TLR2 ligands PAM3CSK4 and MALP-2. PAM3CSK4 and MALP-2
      had preferential IL-10-activating capacities, while the fraction containing
      lysoGPSer plus GPSer had a strong TNF-alpha-inducing capacity. The fraction
      containing lysoGPSer was neutral with respect to pro- vs. anti-inflammatory
      effects. When Th1 and Th2 cytokines were analysed, the schistosomal lipid
      fraction containing lysoGPSer plus GPSer showed a stronger Th2 response compared
      to PAM3CSK4, MALP-2 and lysoGPSer alone. Therefore, the study indicates that not
      only TLR2 ligands derived from bacteria or from parasites can generate distinct
      cytokine profiles but also that the composition of lipid entities reaching the
      immune system can be important in leading to different immune outcomes. This
      information may be important for exploitation of immune modulatory molecules.

PMID- 18086017
TI  - Use of the air pouch model to investigate immune responses to a hookworm vaccine
      containing the Na-ASP-2 protein in rats.
AB  - Hookworms are gastrointestinal nematodes that affect approximately 600 million
      people in developing countries. Using the air pouch model, we have examined the
      effects of vaccination with the recombinant hookworm larval antigen Na-ASP-2 and
      the adjuvant Alhydrogel on the skin immune response to hookworms in Sprague
      Dawley rats. Following vaccination, rats were inoculated 100 Necator americanus
      L3 into the air pouch, and the exudates and cell infiltrates were collected from
      the pouch 24 h later. Larval inoculation induced leucocyte recruitment into the
      pouch. Exudates of rats vaccinated with Na-ASP-2 showed an increase of cytokines
      such as IL-4, IL-10, IFN-gamma and especially, IL-5, as well as IgG1 and IgG2
      antibodies. The increased amount of antigen-presenting cells and cytokines in the
      pouch of vaccinated animals suggests that vaccination could potentially restrain
      this parasite to the inoculation site, avoiding its migration and establishment
      in the host. Moreover, the air pouch model could constitute an alternative to
      screen immune responses to L3 antigens.

PMID- 18086018
TI  - Vaccine testing of a recombinant activation-associated secreted protein (ASP1)
      from Ostertagia ostertagi.
AB  - Previous vaccination trials against the economically important cattle parasite
      Ostertagia ostertagi have indicated the protective capacity of activation
      associated secreted proteins (ASPs). The further development of these antigens
      into a commercial vaccine will require their recombinant expression. The aim of
      the current study was to clone and express Oo-asp1 in a baculovirus expression
      system and to evaluate the protective capacity of the recombinant protein against
      an O. ostertagi challenge infection in cattle. The full coding sequence of Oo
      asp1 was cloned in a baculovirus expression vector in frame with a carboxy
      terminal Histidine tag and recombinant virus was used to infect an insect cell
      culture. Western blot analysis with anti-His and anti-Oo-ASP1 antibodies showed
      the production of recombinant Oo-ASP1. The cell pellet containing the recombinant
      was subsequently used to immunize seven calves three times intramuscularly with
      QuilA as adjuvant. Control animals were solely injected with the QuilA adjuvant.
      The challenge infection with O. ostertagi consisted of 30,000 L3 larvae per
      animal given over 30 days (1000 larvae/day, 5 days/week) and started the same day
      as the final immunization. Immunization with the recombinant Oo-ASP1 did not
      result in any level of protection against the challenge infection. There was no
      reduction in faecal egg output or in worm burdens. Moreover, Western blot
      analyses and ELISA indicated that, although the animals raised an antibody
      response against the recombinant Oo-ASP1, there was hardly a response against the
      native Oo-ASP1, suggesting that the baculovirus expressed recombinant was wrongly
      folded or lacked essential secondary modifications. Further analysis of the
      structure of the native ASPs and their glycosylations is being done.

PMID- 18086020
TI  - Probiotics and oral health effects in children.
AB  - BACKGROUND: Probiotics are living micro-organisms added to food which
      beneficially affect the host by improving its intestinal microbial balance.
      OBJECTIVE: This paper aims to present a general background on probiotics and its
      health effects in children, and to examine the evidence for oral colonization and
      the possible impact on oral health in children and young adults. METHODS: For
      delivery and general health effects, recent systematic reviews, meta-analyses,
      and other relevant papers were used. Concerning oral installation and oral
      effects, a broad search for publications in English was conducted through
      February 2007 in PubMed. Studies describing an installation or intervention trial
      in humans with a controlled design and an oral endpoint measure were considered.
      Fourteen papers with dental focus were identified, of which two were narrative
      reviews. RESULTS: Only one study of dental interest was conducted in children.
      Four papers dealt with oral installation of probiotic bacteria, and although
      detectable levels were found in saliva shortly after intake, the studies failed
      to demonstrate a long-term installation. Seven papers evaluated the effect of
      lactobacilli- or bifidobacteria-derived probiotics on the salivary levels of
      caries-associated bacteria in placebo-controlled designs. All but one reported a
      hampering effect on mutans streptococci and/or yeast. The single study carried
      out in early childhood reported a significant caries reduction in 3- to 4-year
      old children after 7 months of daily consumption of probiotic milk. CONCLUSION:
      Bacteriotheraphy in the form of probiotic bacteria with an inhibitory effect on
      oral pathogens is a promising concept, especially in childhood, but this may not
      necessarily lead to improved oral health. Further placebo controlled trials that
      assess carefully selected and defined probiotic strains using standardized
      outcomes are needed before any clinical recommendations can be made.

PMID- 18086021
TI  - Classification and sequelae of arrested eruption of primary molars.
AB  - AIM: The aim of this study was to classify early arrested eruption of primary
      molars and to analyse and explain the sequelae for the surrounding alveolar bone
      and the succeeding premolar. DESIGN: The position of the arrested primary molars
      in the mandible, the height of the local alveolar bone, and the morphology and
      location of the succeeding premolar were evaluated on radiographs from 29
      children. RESULTS: Four groups of arrest from mild to severe with regards to
      infra-position were categorized (Groups I-IV). Mean ages at the time of referral
      decreased from Groups I (8 years, 10 months) to Group IV (5 years, 9 months).
      SEQUELAE: (i) Reduction of alveolar bone height (Groups I-III); (ii) delayed
      maturity of the succeeding premolar (two-thirds of the cases); (iii) malformation
      of the succeeding premolar (mainly Groups III and IV); and (iv) ectopically
      located premolar occlusal to the retained molar (Group IV). CONCLUSIONS: The
      deeper in the alveolar process a primary molar is retained, the earlier the
      disturbance in the eruption has occurred, and the greater is the risk of the
      permanent tooth germ being malformed and malpositioned. It is estimated that the
      earliest occurrences of arrested eruption of primary molars supposedly occur
      before the age of 3.

PMID- 18086022
TI  - Caries prevalence and distribution in individuals aged 3-20 years in Jonkoping,
      Sweden, over a 30-year period (1973-2003).
AB  - BACKGROUND: Oral health status of individuals aged 3-80 years in the city of
      Jonkoping, Sweden, has been assessed in a series of epidemiological studies over
      a 30-year period. AIM: To analyse the changes in caries prevalence and caries
      distribution in child population sample groups, based on studies performed in
      1973, 1978, 1983, 1993, and 2003. DESIGN: Each time point included 500 randomly
      sampled individuals, divided into age groups of 3, 5, 10, 15, and 20 years.
      Results. Thirty-five per cent of 3-year-olds were caries free in 1973, compared
      with 69% 30 years later. Decayed and filled primary (dfs) and permanent surfaces
      (DFS) were reduced by 50-80% between 1973 and 2003. Adolescents aged 10 and 15
      years exhibited the most pronounced reduction in DFS on the occlusal surfaces. By
      2003, 90% of the proximal carious lesions in 15-year-olds were initial carious
      lesions. In 2003, about 60% of 15-year-olds had a DFS of < or = 5, while about 7%
      exhibited a DFS of > or = 26. CONCLUSIONS: Despite the dramatic decline in the
      prevalence of caries, caries remains a health problem among children,
      particularly those of preschool age. Continuous epidemiological studies are
      recommended to evaluate preventive measures.

PMID- 18086023
TI  - Dental appointment no-shows: why do some parents fail to take their children to
      the dentist?
AB  - BACKGROUND: Children are considerably dependent on their parents, not least in
      relation to achieving good oral health. There is a group of children who do not
      show up for dental treatments or only regular check-ups despite reminders from
      the dental health clinic. The cost of patients failing to come for scheduled
      appointments is also considered significant. AIM: The aim of this study was to
      illuminate the main problem explaining why some parents fail to bring their
      children to the dental health clinics or to encourage and supervise them when
      they can take the responsibility themselves for dental treatments or only regular
      dental check-ups. DESIGN: In-depth interviews were carried out with 16 parents of
      children who regularly had failed to turn up for appointments at the dental
      health clinic. The verbatim transcribed interviews were analysed in line with the
      guidelines for grounded theory. RESULTS: A core category, 'being overloaded in
      daily life', emerged from the data and formed, together with three additional
      related categories, a conceptual model. CONCLUSIONS: Our results indicate that
      these families experience an overload of demands related to their daily living
      and survival. Health-promoting efforts in the form of regular dental check-ups
      for their children have low priority for them.

PMID- 18086024
TI  - A probiotic lozenge administered medical device and its effect on salivary mutans
      streptococci and lactobacilli.
AB  - BACKGROUND: Previous studies have suggested that lactobacilli-derived probiotics
      in dairy products may affect oral ecology, but the effects of different delivery
      methods have received little attention. AIM: The aim of the present study was to
      investigate the effect of the probiotic Lactobacillus reuteri, delivered by a new
      medical device, on the levels of salivary mutans streptococci and lactobacilli in
      young women with high Streptococcus mutans counts. DESIGN: This is a randomized,
      double-blind, placebo-controlled study involving 20 healthy young women (aged 20
      years): 10 as subjects and 10 as controls. The study subjects (Group A) sucked
      the medical device containing the probiotic lozenge with L. reuteri ATCC 55730/L.
      reuteri ATCC PTA 5289 (1.1 x 10(8) CFU) once daily for 10 days, while the control
      subjects (Group B) received placebo medical devices without bacteria. Salivary
      mutans streptococci and lactobacilli were enumerated with chair-side kits at
      baseline and 1 day after the final ingestion. RESULTS: Salivary S. mutans levels
      in the probiotic test group were significantly reduced, with statistical
      significance of reduction (P < 0.05). CONCLUSIONS: A short-term daily ingestion
      of lactobacilli-derived probiotics delivered via medical device containing
      probiotic lozenge reduced the levels of salivary mutans.

PMID- 18086025
TI  - The oro-dental phenotype in Prader-Willi syndrome: a survey of 15 patients.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a rare disorder caused by genetic
      defects in certain regions of chromosome 15q11-13. It is characterized by severe
      neonatal hypotonia and feeding problems, childhood-onset hyperphagia and obesity,
      short stature, facial dysmorphy, hypogonadism, learning and behavioural
      difficulties, and dental abnormalities. AIM: To describe the oro-dental
      phenotypic spectrum of patients with PWS. DESIGN: Fifteen PWS patients (3-35
      years of age) being followed at the Centre for Human Genetics of the University
      Hospital of Leuven were examined at the dental clinic of the same institution.
      Medical information collected included age at diagnosis, body mass index (BMI)
      and level of cognitive functioning. Oral, clinical and radiological evaluations
      were performed. Caries experience (cavitation level), dental erosion and salivary
      flow rates were assessed. RESULTS: The 15 patients had dmft/DMFT scores ranging
      from 0 to 28, while nine were cavity-free. Those with severe caries experience
      also presented advanced dental erosion. BMI ranged from 16 to 42.6. There was no
      association between BMI and caries experience or erosive tooth wear. The PWS
      patients in our survey presented with a more favourable oral health status than
      those in previous studies. This might be due to early diet management or better
      oral hygiene during childhood or both.

PMID- 18086026
TI  - Mothers as facilitators of oral hygiene in early childhood.
AB  - BACKGROUND: Toothbrushing twice daily is a recommended component of oral self
      care soon after the eruption of primary dentition. Aim. This study aims to
      investigate oral hygiene and frequency of oral cleaning in children up to 3
      years, in relation to mother-related factors. DESIGN: A cross-sectional study of
      504 children aged 12-36 months in Tehran, Iran was implemented. Mothers answered
      questions about their own oral self-care and their activity in their children's
      oral hygiene. The child's oral hygiene was assessed on the basis of visible
      dental plaque on the labial surfaces of the upper central incisors. Data analysis
      included chi-square test, analysis of variance (anova) and logistic regression.
      RESULTS: Twice daily oral cleaning was reported for 5% of all children and once
      daily cleaning for 19% of the 12- to 15-month-old children, 18% of the 16- to 23
      month-old children, and 48% of the 24- to 36-month-old children. Of the mothers,
      59% stated that they lacked the skill to clean their children's teeth. Dental
      plaque was observed in 65-76% of the children. Clean teeth were more likely (OR =
      1.7, 95% CI 1.3-2.3) in children of mothers who themselves have a higher
      toothbrushing frequency. CONCLUSIONS: To improve oral hygiene in early childhood,
      more emphasis should be placed on mothers' own toothbrushing and their skills in
      their children's oral cleaning.

PMID- 18086027
TI  - Comparing the caries-preventive effect of two fissure sealing modalities in
      public health care: a single application of glass ionomer and a routine resin
      based sealant programme. A randomized split-mouth clinical trial.
AB  - AIM: The aim of this study was to compare the caries-preventive effect of two
      types of sealant modalities and to evaluate whether the caries-preventive effect
      is related to sealant retention. A hypothesis was tested in which a glass ionomer
      sealant, once applied to the occlusal surface, was able to protect the fissure
      from caries even if the sealant appeared lost at visual inspection. DESIGN: A 3
      year randomized split-mouth trial evaluating two sealant modalities was performed
      at a public health centre in Finland. A chemically curing glass ionomer cement
      (GIC) and light-curing resin-based (RB) sealant material were applied randomly to
      the permanent second molars. Sealant application as a routine treatment procedure
      was carried out to 599 children in the age group of 12-16 years. Caries rate of
      the sealed teeth and sealant retention with both materials were analysed by a
      modified McNemar's test. The effectiveness, rate difference, and relative risk
      with both sealant materials were measured. RESULTS: The difference in caries rate
      between the two modalities was highly significant. When compared to the GIC
      sealant method, the effectiveness of RB sealant method was 74.1% and the rate
      difference 3.2% (95% CI 1.44%, 4.98%). The relative risk for RB-sealed surfaces
      vs. GIC-sealed surfaces of having detectable dentin caries was 0.26 (95% CI 0.12,
      0.57). The retention rate of sealants was higher with RB than GIC (P < 0.001).
      The effectiveness of the retention rate for RB sealants was 94.8% and the rate
      difference 87.2% (95% CI 83.86%, 90.50%). The relative risk during the 3-year
      study period of having a defective or lost RB sealant was 0.052 (95% CI 0.036,
      0.075) when compared to having a defective or lost GIC sealant. CONCLUSION: It is
      concluded that in preventing dentin caries a RB sealant programme including
      resealing when necessary was more effective than a single application of GIC. The
      original hypothesis was thus falsified.

PMID- 18086028
TI  - Bond strength of two total-etching bonding systems on caries-affected and sound
      primary teeth dentin.
AB  - AIM: As bond strength of currently available adhesive systems in caries-affected
      teeth dentin on primary tooth dentin was not well known, the bond strength of two
      bonding systems (PQI and OptiBond Solo Plus) was evaluated on caries-affected and
      sound primary molar tooth dentin and observed the micromorphology of the adhesive
      dentin interfaces. METHODS: By grinding both the sound (n = 30) and caries
      affected (n = 30) approximal surfaces of teeth, flat dentin surfaces were
      obtained. The prepared surfaces were bonded with one of the each adhesive systems
      and a composite resin. After storing the bonded specimens in water at 37 degrees
      C for 24 h, the samples were sectioned and the bond strength of the adhesive
      systems was tested by the microshear test method. The data were statistically
      analysed. RESULTS: Microshear bond strengths of PQI group for caries-affected and
      sound primary tooth dentin were 9.43 +/- 2.44 (MPa) and 9.32 +/- 2.95 (MPa) (P >
      0.05), respectively, and the bond strengths of OptiBond Solo Plus group for
      caries-affected and sound primary tooth dentin were 15.33 +/- 3.59 (MPa) and
      11.96 +/- 2.30 (MPa) (P < 0.05), respectively. Micromorphological features
      between sound and caries-affected dentin were similar in both PQI and OptiBond
      Solo Plus groups. CONCLUSION: Both the adhesives showed significantly different
      bond strengths in caries-affected dentin but showed similar bond strengths in
      sound dentin.

PMID- 18086029
TI  - Common use of a Fear Survey Schedule for assessment of dental fear among children
      and adults.
AB  - BACKGROUND: Little is known about children with dental fear (DF) in a long-term
      perspective. Measures of DF suitable for use among children, adolescents, and
      adults would be of value for longitudinal and family studies. AIM: Our aim was to
      explore the DF subscale of the Children's Fear Survey Schedule (CFSS-DS) in
      highly fearful adult dental patients. DESIGN: The subjects were 230 adult
      patients applying for treatment for severe DF at a specialized DF clinic.
      Questionnaires investigated background data, general fear and DF, and general
      anxiety and depression. Reference data were obtained from 36 nonfearful patients
      on a subset of questionnaires. RESULTS: The fearful group reported high levels of
      DF on all measures and at a level similar to children with severe DF. The DF
      measures clearly differed between the fearful and reference groups. A factor
      analysis revealed a three-factor structure (fear of dental treatment, medical
      treatment, and of strangers and choking), which explained 68% of the variance.
      CONCLUSION: The CFSS-DS appears suitable for use in studies of adult populations.
      The results indicated that some areas of DF (physiology, avoidant behaviour,
      anticipatory anxiety), areas of importance among adult patients, are not assessed
      by the CFSS-DS. Studies of adults should therefore also include established adult
      measures of DF.

PMID- 18086031
TI  - Naturally occurring bacteraemia in American lobsters, Homarus americanus Milne
      Edwards, in Long Island Sound.
AB  - The health status of the American lobster, Homarus americanus Milne-Edwards, in
      Long Island Sound (LIS) has been in decline, with seasonal mortality events
      occurring since 1998. In order to assess the potential effects of environmental
      conditions on lobster health via haemolymph analysis, lobsters collected from
      various sites in LIS were examined and sampled while concurrent environmental
      data (water temperature, salinity and dissolved oxygen) were recorded. The pH of
      the haemolymph of each lobster was tested, followed by a collection of haemolymph
      for serum biochemistry analysis and bacterial culture. This report focuses on the
      results of the bacterial sampling. The majority of bacteria cultured were
      opportunistic pathogens commonly found in the environment, including some that
      are associated with sewage and pollution. The prevalence of bacteraemia was
      correlated with the site of collection, the month in which the lobsters were
      sampled, and water temperature.

PMID- 18086030
TI  - A review on the morphology, molecular characterization, morphogenesis and
      pathogenesis of white spot syndrome virus.
AB  - Since it first appeared in 1992, white spot syndrome virus (WSSV) has become the
      most threatening infectious agent in shrimp aquaculture. Within a decade, this
      pathogen has spread to all the main shrimp farming areas and has caused enormous
      economic losses amounting to more than seven billion US dollars. At present,
      biosecurity methods used to exclude pathogens in shrimp farms include
      disinfecting ponds and water, preventing the entrance of animals that may carry
      infectious agents and stocking ponds with specific pathogen-free post-larvae. The
      combination of these practices increases biosecurity in shrimp farming facilities
      and may contribute to reduce the risk of a WSSV outbreak. Although several
      control methods have shown some efficacy against WSSV under experimental
      conditions, no therapeutic products or strategies are available to effectively
      control WSSV in the field. Furthermore, differences in virulence and clinical
      outcome of WSSV infections have been reported. The sequencing and
      characterization of different strains of WSSV has begun to determine aspects of
      its biology, virulence and pathogenesis. Knowledge on these aspects is critical
      for developing effective control methods. The aim of this review is to present an
      update of the knowledge generated so far on different aspects of WSSV
      organization, morphogenesis, pathology and pathogenesis.

PMID- 18086032
TI  - Renal myxozoanosis in weedy sea dragons, Phyllopteryx taeniolatus (Lacepede),
      caused by Sinuolinea phyllopteryxa n. sp.
AB  - Renal myxozoanosis was diagnosed histologically in 11 captive, wild caught, adult
      weedy (common) sea dragons, Phyllopteryx taeniolatus, from three separate public
      aquaria in the United States. Myxozoan spores were visible in wet mounts of
      kidney tissue and were associated with renal tubular dilatation and tubular
      epithelial cell hypertrophy. Light and electron microscopy revealed spore
      morphology consistent with the genus Sinuolinea. Spores were spheroidal, slightly
      dorso-ventrally compressed, length (L) 17.1 x width (W) 16.4 x thickness (T) 15.6
      microm, with two shell valves joined at a distinct, sinuous sutural ridge, and
      had two nearly spherical polar capsules, L 5.5 x W 5.0 microm, with five to seven
      turns of the polar filament. There were no extra-valvular ridges or protrusions.
      DNA sequencing required the design of three new primers that yielded 1740 bp of
      18S ribosomal DNA sequence. The parasite was determined to be novel based on
      morphological and molecular data, and was given the name Sinuolinea phyllopteryxa
      after its vertebrate host.

PMID- 18086033
TI  - Genetic analysis of infectious pancreatic necrosis virus from Scotland.
AB  - Infectious pancreatic necrosis (IPN) is a highly contagious disease of young
      salmonid fish, and is one of the most serious economic diseases in aquaculture.
      In Scotland, an increase in IPN virus (IPNV) outbreaks in seawater Atlantic
      salmon, Salmo salar, has been reported in recent years. The aim of this study was
      to analyse the VP2 gene from recent IPNV isolates from Scotland, to determine
      whether there are epidemiological links between IPNV isolates from farms (13),
      wild fish (17) and the environment (6) in order to investigate potential wild and
      farmed fish interactions. Comparison of the nucleotide sequence of the VP2 gene
      revealed that 34 of 36 isolates were 97.1-100% similar and the deduced amino acid
      sequences showed 97-100% identity. Two isolates from wild fish exhibited the most
      divergence at 85-87.3% similarity to the other isolates at the nucleotide level
      and 88.2-90.8% identity at the deduced amino acid level. Phylogenetic analyses
      revealed that 34 of 36 of the isolates from Scotland were genetically closely
      related to the A2 (Sp) serotype of IPNV. The two wild isolates from seatrout,
      Salmo trutta, and flounder, Platichthys flesus, were most closely related to the
      European A5 (Te) serotype. This study represents a comprehensive IPNV
      phylogenetic study that indicates that there are closely related or identical
      isolates in circulation in the marine environment, which adds evidence that
      disease interactions between wild and farmed fish may occur. This type of
      analysis is a useful tool in the management and control of fish diseases because
      it can assist in the identification of epidemiological links and highlight
      potential risks to aquaculture.

PMID- 18086034
TI  - Isolation and quantification of infectious pancreatic necrosis virus from ovarian
      and seminal fluids of Atlantic salmon, Salmo salar L.
AB  - Methods for the isolation and quantification of infectious pancreatic necrosis
      virus (IPNV) from ovarian and seminal fluids of Atlantic salmon are described.
      Both have utility for the non-lethal detection of IPNV in mature broodstock and
      for research into vertical transmission. Two experiments are described to check
      the efficiency of an elution method for the removal of IPNV from milt. The
      isolation rate for ovarian fluid of females was generally higher than that for
      seminal fluid of males from the same populations. In IPNV milt mixing experiments
      up to 99.98% of available IPNV adsorbed to Atlantic salmon spermatozoa and 20
      100% of virus eluted using a variety of procedures. Titration of virus from
      naturally infected milt can be useful in estimating the relative vertical
      transmission risk from male broodstock.

PMID- 18086035
TI  - The influence of salmon surface mucus on the growth of Flavobacterium columnare.
AB  - Flavobacterium columnare is the causative agent of columnaris disease. The
      presence of lesions on the gills, skin and fins of diseased fish suggests that F.
      columnare is able to utilize fish skin mucus as a substrate for growth and that
      exposure to this material would alter the expression of genes involved in the
      colonization of the outer surfaces of the fish. Growth, biofilm formation,
      extracellular protease production and changes in protein expression of F.
      columnare strain C#2 cultured in media supplemented with juvenile Atlantic salmon
      skin mucus were compared with the same media without mucus. C#2 was able to grow
      by using mucus as the sole nutrient source. Growth in mucus-containing media
      induced cells to grow as a biofilm and extracellular protease activity increased
      in mucus-containing cultures. SDS-PAGE protein profiles showed that expression of
      six extracellular proteins increased in mucus-containing media. These results
      demonstrate that salmon surface mucus promotes the growth of F. columnare and
      that exposure to mucus alters the growth characteristics of this bacterium with
      regard to protease production and biofilm formation. Further characterization of
      mucus-induced physiological changes will increase our understanding of the basis
      of virulence of this economically important fish pathogen.

PMID- 18086036
TI  - Detection of koi herpes virus (CyHV-3) in goldfish, Carassius auratus (L.),
      exposed to infected koi.

PMID- 18086037
TI  - Susceptibility of Photobacterium damselae subsp. piscicida strains isolated from
      Senegalese sole, Solea senegalensis Kaup, and gilthead seabream, Sparus aurata
      L., to several antibacterial agents.

PMID- 18086038
TI  - Differential susceptibility of blue catfish, Ictalurus furcatus (Valenciennes),
      channel catfish, I. punctatus (Rafinesque), and blue x channel catfish hybrids to
      channel catfish virus.

PMID- 18086039
TI  - The benefits of breastfeeding or the harm of formula feeding?

PMID- 18086040
TI  - Paediatric cardiopulmonary resuscitation: recent changes to guidelines.
AB  - Recommended cardiopulmonary resuscitation guidelines for infants and children by
      health-care personnel have been updated following an extensive review of the
      science of resuscitation. Notable changes include a change to a single chest
      compression-to-ventilation ratio of 15:2, a single DC shock (2 J/kg) strategy for
      shockable rhythms followed by immediate uninterrupted cardiopulmonary
      resuscitation for 2 min, use of amiodarone (5 mg/kg) for DC-shock resistant
      rhythms, the routine use of carbon dioxide detection to confirm correct
      endotracheal tube placement and the use of therapeutic hypothermia if the victim
      fails to resume consciousness after resuscitation.

PMID- 18086041
TI  - Wheezy swallow: poorly responsive 'asthma'.
AB  - We report two children who presented with cough and wheeze, were initially
      misdiagnosed with asthma and were subsequently demonstrated to have achalasia as
      the underlying cause of their symptoms. These cases highlight the importance of
      considering diagnoses other than asthma when there is a suboptimal response to
      asthma medications, as well as the value of investigations including chest X-ray
      and pulmonary function tests in establishing the underlying cause.

PMID- 18086042
TI  - Upper airway size while sucking on a pacifier in an infant with micrognathia.
AB  - In an infant with micrognathia, who was being evaluated after an apparent life
      threatening event, respiration timed lateral radiographs showed an increase in
      the width of the middle airway space during inspiration from 2 mm without the
      pacifier to 9 mm while sucking on a pacifier. This observation is consistent with
      the hypothesis that the well-documented association between the pacifier use and
      reduced risk of sudden infant death syndrome may be at least in part related to
      changes in airway size.

PMID- 18086043
TI  - Cytomegalovirus-associated ileal stricture in a preterm neonate.
AB  - Gastrointestinal (GI) manifestations of post-natally acquired cytomegalovirus
      (CMV) in preterm neonates can vary from mild diarrhoea to severe necrotising
      enterocolitis. However, the suspicion of CMV-related GI disease remains low. Mild
      CMV disease localised to the GI tract may go undiagnosed initially until a more
      obvious complication such as strictures manifest. A case of CMV-associated
      enteritis in an extremely preterm neonate is presented. The diagnosis was
      established after the histopathology of the surgical specimen showed the presence
      of CMV inclusion bodies. Testing the stool specimen for CMV to establish the
      diagnosis when the pathology is limited to the GI tract is also discussed.

PMID- 18086044
TI  - Hypnic headache in childhood: a new case report.

PMID- 18086045
TI  - Re: Amplitude-integrated electroencephalography in infants with neonatal
      encephalopathy.

PMID- 18086046
TI  - Role of glycosaminoglycans for binding and infection of hepatitis B virus.
AB  - Many parts of the life cycle of hepatitis B virus (HBV) infection of hepatocytes
      have been unravelled, but the attachment and entry process leading to infection
      is largely unknown. Using primary Tupaia hepatocyte cultures as an in vitro
      infection system, we determined that HBV uses cell-surface heparan sulfate
      proteoglycans as low-affinity receptor, because HBV infection was inhibited by
      heparin (IC50: 5 microg ml(-1)) or other higher-sulfated polymers, but not by
      lower-sulfated glycosaminoglycans, such as chondroitin sulfate. Pretreatment of
      primary hepatocytes with heparinase decreased viral binding and inhibited HBV
      infection completely. Interestingly, after preS1-dependent viral binding at 16
      degrees C to the cell surface, subsequent infection could still be inhibited by
      HBV preS1-lipopeptides, but not by heparin any more, suggesting a shift of the
      virus to a high-affinity receptor. In summary, we suggest following multistep
      attachment process: in vivo, HBV is initially trapped within the liver in the
      space of Disse by heparan sulfate proteoglycans. Thereafter, HBV binds via its
      preS1 attachment site and the N-terminal myristic acid to a yet unknown, high
      affinity receptor that confers uptake in a yet unknown compartment.

PMID- 18086048
TI  - A randomized, bilateral, prospective comparison of calcium hydroxylapatite
      microspheres versus human-based collagen for the correction of nasolabial folds.
AB  - BACKGROUND: Current soft tissue fillers are a compromise between ease of use,
      duration of correction, reactivity, and cost. A product utilizing calcium
      hydroxylapatite (CaHA) is currently being used as a soft tissue filler.
      OBJECTIVE: The objective was to compare the efficacy and safety of CaHA
      microspheres versus human-based collagen for the correction of nasolabial folds.
      MATERIALS AND METHODS: Four centers enrolled 117 subjects with moderate to deep
      nasolabial folds. Subjects received CaHA on one side of the face and human
      collagen on the other. Up to two touch-ups were allowed. A blinded panel of
      experts evaluated subject photographs from initial and follow-up visits. RESULTS:
      Seventy-nine percent of subjects had superior improvement on the CaHA side
      through 6 months (p<.0001). For optimal correction, significantly less volume and
      fewer injections were needed for CaHA than for collagen (p<.0001). Adverse event
      rates were comparable, with some increase in bruising and edema for CaHA-treated
      sides. Adverse event duration was similar for both groups and generally resolved
      within 14 to 21 days. CONCLUSION: This CaHA-based product gives significantly
      longer-lasting correction of nasolabial folds compared to human collagen. Less
      total material and fewer injections are required. The adverse event profile of
      the product is similar to the collagen-based product.

PMID- 18086049
TI  - A multicenter, 47-month study of safety and efficacy of calcium hydroxylapatite
      for soft tissue augmentation of nasolabial folds and other areas of the face.
AB  - OBJECTIVES: Each soft tissue filler product has its own unique profile in terms
      of adverse events. In this large-scale study, we investigated the safety profile
      of Radiesse, an injectable calcium hydroxylapatite (CaHA) implant, in treatment
      of nasolabial folds and other areas of the face. We also investigated the
      efficacy in a subset of the larger patient group. METHODS: After obtaining
      informed consent from the subjects, researchers injected CaHA at two treatment
      centers into 113 patients (100 women and 13 men, ranging in age from 26 to 78
      years) for a variety of facial aesthetic applications over a period of 47 months.
      Seventy-five patients had a single injection session; 38 had multiple sessions.
      Most patients (102) received 1.0 mL of CaHA per session; 12 received 2.0 mL per
      session. Typically, CaHA was administered with a 27-gauge 0.5- or 1 1/4-in.
      needle. RESULTS: Safety. Of 113 patients, only 7 reported minor adverse events
      that were short-term and resolved within 1 month: transient ecchymosis (3),
      nongranulatomous submucosal nodules of the lip (2), and inflammation and edema
      (2). Efficacy. Efficacy ratings were performed for a subset of patients (n=41).
      On a scale of 1 to 5 (1=unsatisfactory; 5=excellent), the mean patient evaluation
      score for look and feel of the implant was 4.6; the mean physician scores for the
      look and feel of the implant were 4.5 and 4.6, respectively. During the 6-month
      follow-up visit, patients' mean ratings of the look and feel of the implant were
      4.8 and 4.9, respectively. The physician's mean ratings for the look and feel of
      the implant were 4.5 and 4.9, respectively. CONCLUSIONS: In our study, CaHA
      performed well, with a favorable safety profile, high patient satisfaction (90%
      of patients reported very good or excellent results), and good durability. We are
      especially pleased with the low incidence of adverse events coupled with the
      favorable responses from the patients themselves due to longevity of correction.

PMID- 18086051
TI  - Novel synthetic dermal fillers based on sodium carboxymethylcellulose: comparison
      with crosslinked hyaluronic acid-based dermal fillers.
AB  - BACKGROUND: The persistence of dermal fillers containing crosslinked hyaluronic
      acid (XLHA) correlates linearly to the concentration of polymer in solution. For
      dermal fillers composed of XLHA, a polymer concentration above approximately 25
      mg/mL is not practical because it cannot be easily injected through a small-bore
      needle. OBJECTIVE: Formulating dermal fillers from mixtures of
      carboxymethylcellulose (CMC) and polyethylene oxide (PEO) has several advantages
      over XLHA. We hypothesize that increasing the concentration of CMC/PEO will
      increase the persistence in the dermis. These polymers of CMC and PEO can be
      formulated at higher concentrations than XLHA to produce smooth, particulate-free
      gels resulting in easier, more controllable injection. Second, these gels are not
      required to be covalently crosslinked; CMC/PEO forms a stable gel-like structure
      in solution without crosslinking. MATERIALS AND METHODS: Here we have prepared
      dermal fillers from CMC/PEO polymer blends at concentrations of 20 mg/mL (dermal
      filler 1), 29 mg/mL (dermal filler 2), 37 mg/mL (dermal filler 3), and 45 mg/mL
      (dermal filler 4) and measured their rheologic properties compared to commercial
      XLHA dermal fillers. RESULTS AND CONCLUSIONS: The data here demonstrate that it
      is possible to duplicate the rheologic properties of commercial XLHA fillers
      using CMC/PEO at different polymer concentrations to formulate improved dermal
      fillers. All of the dermal filler formulations prepared can be easily injected
      through 30-gauge needles.

PMID- 18086050
TI  - Comparison of smooth-gel hyaluronic acid dermal fillers with cross-linked bovine
      collagen: a multicenter, double-masked, randomized, within-subject study.
AB  - BACKGROUND: A new family of next-generation non-animal hyaluronic acid (HA)
      dermal fillers was approved by the FDA in June 2006. Compared with other HA
      fillers available in the United States at the time of writing, these new fillers
      have a higher concentration of HA, higher concentration of cross-linked HA, and a
      smooth consistency--which should promote long-lasting corrections and a smooth,
      natural look and feel postinjection. OBJECTIVE: The objective was to compare the
      effectiveness and safety of these smooth-gel HA dermal fillers with bovine
      collagen for nasolabial fold (NLF) correction. METHODS AND MATERIALS: A total of
      439 subjects with moderate or severe NLFs received one of three types of smooth
      gel HA dermal filler (in one NLF) and cross-linked bovine collagen (in the other
      NLF) and were evaluated for <or=24 weeks. RESULTS: All three HA dermal fillers
      achieved considerably longer-lasting clinical correction than bovine collagen;
      81% to 90% of HA dermal filler-treated NLFs maintained a clinically significant
      improvement from baseline for >or=6 months. Up to 88% of subjects preferred the
      HA dermal fillers over bovine collagen. All fillers were similarly well
      tolerated. CONCLUSION: The smooth-gel HA dermal fillers offer longer-lasting
      correction than bovine collagen-which may lessen the frequency that repeat
      treatments are needed. Also, they were preferred by the vast majority of subjects
      which should promote patient satisfaction.

PMID- 18086052
TI  - A multicenter, randomized trial comparing calcium hydroxylapatite to two
      hyaluronic acids for treatment of nasolabial folds.
AB  - INTRODUCTION: In this study, we examined Radiesse (calcium hydroxylapatite;
      CaHA), Juvederm 24 (hyaluronic acid; HA-1A), Juvederm 24HV (HA-1B), and Perlane
      (HA-2) for patient satisfaction, likelihood to return, immediate efficacy, and
      duration of correction. OBJECTIVE: This multicenter, blinded, randomized study
      compares patient satisfaction variables, efficacy, and durability of CaHA gel and
      HA for correction of nasolabial folds (NLFs) through 12 months after 4-month
      touch-up. METHODOLOGY: A total of 205 randomized patients received either CaHA
      gel or HA for NLF treatment at initial visit and 4-month touch-up. Patients
      returned at 4, 8, and 12 months after the second injection for evaluation.
      Surveys measured patient satisfaction; effectiveness measures included the Global
      Aesthetic Improvement Scale (GAIS). RESULTS: More CaHA gel patients were
      satisfied or extremely satisfied than each HA tested. At 8 months, significantly
      more CaHA gel-treated NLFs were improved on the GAIS than any HA. The volumes of
      CaHA gel and three HA materials injected through 4 months were 2.2, 2.9, 4.8, and
      2.9 mL, respectively (p<.005). No serious adverse events were observed.
      CONCLUSIONS: In this controlled study, CaHA gel ranked highest in patient
      satisfaction and likelihood to return. The material was more effective and longer
      lasting than each HA in maintaining NLF augmentation.

PMID- 18086053
TI  - Skin test hypersensitivity study of a cross-linked, porcine collagen implant for
      aesthetic surgery.
AB  - BACKGROUND: The use of bovine collagen implants for dermal contour correction is
      associated with a 3% to 5% incidence of hypersensitivity, which necessitates
      pretreatment screening by an intradermal skin test. OBJECTIVE: The objective was
      to determine the incidence of hypersensitivity with the recently developed cross
      linked, porcine collagen implant, EVOLENCE (ColBar LifeScience Ltd.), which is
      used intradermally for correction of rhytids and scars. MATERIALS AND METHODS:
      Enrolled subjects (n=530) received an intradermal injection of 0.1 mL EVOLENCE
      implant in the left forearm and a second injection in the right forearm after 2
      weeks. Injection sites were assessed clinically at 30 minutes and 72 hours after
      each injection and at 30 days after the second injection. Serum anticollagen
      antibody determinations were performed at screening and at the end of the study.
      RESULTS: Study assessments were completed by 519 subjects. No significant
      erythematous reactions suggestive of positive hypersensitivity were observed.
      Most subjects did not display antibodies against porcine Type I collagen at any
      time, and those who did showed no changes in levels during the study. The single
      sided 95% upper confidence limit for the possibility of moderate-to-severe
      erythematous reactions with the EVOLENCE implant was determined as 0.58% of
      subjects. CONCLUSION: Because the EVOLENCE implant has a low potential for
      hypersensitivity, intradermal skin testing before its use appears unnecessary.

PMID- 18086054
TI  - A single-center, open-label study on the use of injectable poly-L-lactic acid for
      the treatment of moderate to severe scarring from acne or varicella.
AB  - BACKGROUND AND OBJECTIVE: Acne scars may negatively impact quality of life. The
      purpose of this study was to collect preliminary data on the efficacy and safety
      of injectable poly-L-lactic acid (PLLA, Sculptra, Dermik Laboratories) for the
      treatment of acne scars. METHODS: Twenty subjects aged 42.4+/-10.7 years (10 men,
      10 women) with facial scars resulting from moderate to severe acne or varicella
      participated in this single-center, open-label prospective study. The primary end
      point was the resolution of the acne or varicella scars. Secondary end points
      were the physician and subject assessments of scar improvement. PLLA
      reconstituted with 5 mL of sterile water was injected serially at or near the
      sites of the acne scars without topical anesthesia. RESULTS: Investigator
      assessed reductions in acne scar size and severity were significant (p<.0001)
      during the course of seven treatments. Subject-rated reduction in scar severity
      was also significant (p=.0078). Subject satisfaction with treatment trended
      toward an increase with each treatment session and approached significance
      (p=.0899). Adverse events were limited to depression (n=1) not related to the
      treatment. CONCLUSION: Injectable PLLA as used in this investigation appears to
      correct the types of acne scars treated in this study without serious adverse
      effects.

PMID- 18086055
TI  - Normal and pathologic tissue reactions to soft tissue gel fillers.
AB  - BACKGROUND: All gels act as foreign bodies. Host response ranges from a few
      macrophages to an intense foreign-body reaction with fibrosis, depending on gel
      type. For polymer gels the filling effect stems from their volume. For
      combination gels it stems from the intended host foreign-body reaction to the
      microparticles. OBJECTIVE: This review explains how host tissue reacts with
      different gel types and how adverse reactions differ depending on gel type.
      METHODS AND MATERIALS: This study is based on observations during the past 6 1/2
      years from experimental/clinical studies and biopsies from adverse reactions.
      RESULTS: Hydrophilic polymer gels constantly exchange water with their host
      tissue with minimal fibrosis. Degradable gels are encircled and degraded by
      macrophages; polyacrylamide gel is traversed by macrophages, replaced by fibrous,
      vessel-bearing strands. All other gels provoke a foreign-body reaction with
      ensuing fibrosis. Adverse reactions include bacterial infection for the
      hydrophilic gels and a fibrous granuloma for all other gel types. It is
      hypothesized that bacteria are maintained within a biofilm (a film comprising
      bacteria, their nutrients, and their waste products) giving rise to a low-grade
      infection. CONCLUSIONS: Infectious nodules must be treated with antibiotics.
      Granulomas must be treated with a combination of both steroids and antibiotics or
      excision.

PMID- 18086056
TI  - Immunogenicity studies of cosmetically administered nonanimal-stabilized
      hyaluronic acid particles.
AB  - BACKGROUND: Hypersensitivity resulting from humoral or cellular immunologic
      mechanisms is the least well-documented of adverse events associated with dermal
      fillers. OBJECTIVE: Humoral and cellular immunogenicity of nonanimal-stabilized
      hyaluronic acid (NASHA) was studied in prospective clinical trials involving
      nasolabial fold augmentation. METHODS: In two randomized clinical studies, 150
      (10 centers) and 283 (17 centers) subjects received NASHA as Restylane and/or
      Perlane (both QMed, Uppsala, Sweden; mean, 69 mg) for dermal augmentation. Serum
      immunoglobulin (Ig)E and IgG anti-NASHA were measured by immunoassay at 0, 6, and
      24 weeks and IgE anti-NASHA by intradermal skin testing (ID-ST) at 0 and 24
      weeks. The 24-week ID-ST site was biopsied 3 days later for histopathologic
      evidence of cell-mediated immunity. RESULTS: Of 433 subjects, 42 systemic adverse
      experiences were reported by 37 participants; all but 1 were judged by
      investigators to be unrelated to NASHA administration. All ID-STs and IgE anti
      NASHA results were negative, indicating no IgE sensitization. Serologically,
      91.8% of 425 subjects were negative for IgG anti-NASHA (<1.5 microg/mL) at all
      time points, whereas 7.8% had positive enrollment IgG anti-NASHA (range, 1.5-18.5
      microg/mL) that remained essentially unchanged over the study period. The 24-week
      ID-ST biopsies showed no histological evidence for NASHA-induced cell mediated
      lymphocytic inflammatory reactions (Type IV hypersensitivity) or superficial
      dermal edema (Type 1 hypersensitivity). CONCLUSION: NASHA administration does not
      elicit clinical/laboratory evidence for cellular or humoral immune responses in
      98% of individuals, supporting the conclusion that Restylane and/or Perlane are
      not commonly immunogenic or allergenic.

PMID- 18086057
TI  - The long-term host response to liquid silicone injected during soft tissue
      augmentation procedures: a microscopic appraisal.
AB  - BACKGROUND: Silicone has a long history of use as a soft tissue filler. MATERIALS
      AND METHODS: As a contribution to the clarification of the role and fate of this
      material when used as a filler in soft tissue augmentation techniques, 35 skin
      biopsies were examined by light microscopy. These biopsies were obtained from
      target areas where liquid silicone had been injected in 25 patients between 1 and
      23 years prior, for the correction of depressed scars on the face. RESULTS: The
      microscopic study revealed in 100% of the cases the continued presence, in
      significant amounts, of the silicone previously injected into the target areas,
      where it failed to elicit any significant adverse reaction. CONCLUSION: Owing to
      its high permanence and to its inertness, reflected by the lack of any adverse
      reaction to its presence in the target site, silicone should be regarded as a
      valuable filler, at least for the correction of small depressed facial scars.

PMID- 18086058
TI  - Late-appearing abscesses after injections of nonabsorbable hydrogel polymer for
      HIV-associated facial lipoatrophy.

PMID- 18086059
TI  - Early and late complications after a nonabsorbable hydrogel polymer injection: a
      series of 14 patients and novel management.

PMID- 18086060
TI  - Filler rhinoplasty.

PMID- 18086061
TI  - A randomized, multicenter study of the safety and efficacy of Dermicol-P35 and
      non-animal-stabilized hyaluronic acid gel for the correction of nasolabial folds.
AB  - BACKGROUND: Non-animal-stabilized hyaluronic acid (NASHA) offers longer-lasting
      cosmetic improvement and reduced risk of hypersensitivity and requires less
      injection volume than bovine collagen-derived dermal fillers. Porcine collagen
      derived Dermicol-P35 has low immunogenicity and has the potential to provide
      durability at least equivalent to that of NASHA. OBJECTIVE: The objective was to
      evaluate the efficacy and safety of Dermicol-P35 and NASHA for correction of
      nasolabial folds (NLFs). METHODS AND MATERIALS: A total of 149 subjects with
      moderate NLFs were randomized to receive Dermicol-P35 and NASHA on contralateral
      sides of the face. If needed, subjects could receive a repeat injection 2 weeks
      later to obtain an optimal cosmetic result (OCR). RESULTS: Significant (p<.001)
      improvement in the Modified Fitzpatrick Wrinkle Scale scores relative to
      screening was observed after treatment with Dermicol-P35 and NASHA. Relative to
      the OCR visit, mean scores increased (p<.001) over time, but there were no
      significant differences between treatments (+0.39 and +0.37 at 6 months; p=.626).
      Greater proportions of subjects experienced swelling, bruising, and pain at the
      NASHA site. Several subjects had more induration at the Dermicol-P35 site. There
      was no evidence of any adverse immunologic effect. CONCLUSION: The effectiveness
      of Dermicol-P35 is maintained for at least 6 months and is equivalent to NASHA
      for the correction of NLFs.

PMID- 18086062
TI  - Five-year safety and efficacy of a novel polymethylmethacrylate aesthetic soft
      tissue filler for the correction of nasolabial folds.
AB  - BACKGROUND: A novel soft tissue filler composed of polymethylmethacrylate (PMMA)
      microspheres suspended in a collagen gel matrix containing 0.3% lidocaine
      (ArteFill, Artes Medical, Inc.) was recently approved by the Food and Drug
      Administration for the correction of nasolabial folds. A randomized, multicenter,
      controlled pivotal trial performed in the United States established the safety
      and efficacy of this medical device throughout a 12-month study period.
      OBJECTIVE: The objective was to substantiate the long-term 5-year safety and
      efficacy of this novel soft tissue PMMA filler. METHODS AND MATERIALS: Attempts
      were made to contact all subjects treated with the PMMA filler that were enrolled
      in the original pivotal study. Safety was assessed by standard adverse event
      reporting methods. Efficacy was determined using a validated six-point facial
      fold assessment photometric grading scale using blinded observers' assessment of
      standardized photographs. RESULTS: Subjects (n=119) demonstrated significant
      improvement in nasolabial folds comparing baseline (before any treatment) to 5
      years after their last treatment (p<.001). Notably, subjects also demonstrated
      continued improvement between 6 months after their last treatment and Year 5
      (p=.002). No serious unanticipated device-related adverse events were reported.
      CONCLUSION: This PMMA filler is the first soft tissue filler to demonstrate
      continued improvement and persistence of correction over a 5-year period
      posttreatment.

PMID- 18086063
TI  - Epidural analgesia: first do no harm.

PMID- 18086064
TI  - Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis
      of randomised controlled trials.
AB  - We conducted a systematic review of the effects of dexmedetomidine on cardiac
      outcomes following non-cardiac surgery. We included prospective, randomised peri
      operative studies of dexmedetomidine that reported mortality, cardiac morbidity
      or adverse drug events. A PubMed Central and EMBASE search was conducted up to
      July 2007. The reference lists of identified papers were examined for further
      trials. Of 425 studies identified, 20 were included in the meta-analysis (840
      patients). Dexmedetomidine was associated with a trend towards improved cardiac
      outcomes; all-cause mortality (OR 0.27, 95% CI 0.01-7.13, p = 0.44), non-fatal
      myocardial infarction (OR 0.26, 95% CI 0.04-1.60, p = 0.14), and myocardial
      ischaemia (OR 0.65, 95% CI 0.26-1.63, p = 0.36). Peri-operative hypotension (26%,
      OR 3.80, 95% CI 1.91-7.54, p = 0.0001) and bradycardia (17%, OR 5.45, 95% CI 2.98
      9.95, p < 0.00001) were significantly increased. An anticholinergic did not
      reduce the incidence of bradycardia (p = 0.43). A randomised placebo-controlled
      trial of dexmedetomidine is warranted.

PMID- 18086065
TI  - Therapeutic hypothermia in comatose patients after out-of-hospital cardiac
      arrest.
AB  - Our intensive care unit has been treating comatose patients, following an out-of
      hospital cardiac arrest, with therapeutic hypothermia since 2002. In all, 139 out
      of-hospital cardiac arrest patients were admitted in the 4-year period 2002-5. Of
      these, 27% had a favourable outcome (discharged home or to rehabilitation). Forty
      one per cent of patients presenting with ventricular fibrillation (VF) and 7% of
      non-VF patients had a favourable outcome. No patient with an estimated time from
      collapse to first attempt at cardiopulmonary resuscitation over 12 min survived
      to hospital discharge. Twenty-two per cent of patients over 70 years were
      discharged home, suggesting age was not a barrier to surviving out-of-hospital
      cardiac arrest. The introduction of a therapeutic hypothermia clinical pathway,
      at the end of 2003 improved the efficiency of cooling. The percentage of patients
      cooled to below 34 degrees C within 4 h increased from 15 to 51% and those cooled
      for more than 12 h increased from 30 to 83%.

PMID- 18086066
TI  - Peritonsillar infiltration with bupivacaine and pethidine for relief of post
      tonsillectomy pain: a randomised double-blind study.
AB  - Previous studies of infiltration of local anaesthetics in children undergoing
      tonsillectomy resulted in conflicting results. The aim of this study was to
      evaluate the effect of the peritonsillar injection of bupivacaine and pethidine
      on postoperative pain in children undergoing snare-dissection tonsillectomy. In a
      double-blind study, 80 children (aged 7-15 years) were randomly divided into two
      groups receiving peritonsillar injection of either bupivacaine (1 mg x kg(-1))
      and pethidine (1 mg x kg(-1)) in adrenaline 1:200,000 (treatment group) or an
      equivalent volume of saline (placebo group) pre-operatively. The time needed for
      first demand of analgesia and analgesic consumption to reduce the visual analogue
      scale (VAS) for resting throat pain to < or = 30, the VAS for pain on swallowing,
      drinking liquid and eating a soft diet, incidence of nausea and vomiting, and the
      need for rescue anti-emetics in the first 24 h after operation were compared in
      both groups. The combination of bupivacaine and pethidine could significantly
      decrease the consumption of analgesics for resting pain at 4, 6, 8, 12, and 24 h
      after operation but did not reduce pain on swallowing, drinking liquid and eating
      a soft diet. The times to demand of first dose of analgesic and to first oral
      intake were not significantly different. The overall satisfaction of patients in
      relation to relief of postoperative pain was not significantly different between
      the two groups. Although peritonsillar injection of pethidine and bupivacaine in
      children reduces the analgesic consumption, it does not affect the dynamic pain
      state in the first 24 h after snare-dissection tonsillectomy.

PMID- 18086067
TI  - Airtraq vs standard laryngoscopy by student paramedics and experienced
      prehospital laryngoscopists managing a model of difficult intubation.
AB  - Two consecutive, randomised, cross-over trials compared intubation success rates
      in third-year paramedic students and experienced prehospital practitioners using
      the Airtraq or a Macintosh laryngoscope with flexible stylet in a manikin model
      of a Cormack and Lehane grade III/IV laryngoscopic view. First-time intubation
      rates for the Macintosh and Airtraq for students were 0/23 (0%) vs 10/23 (44%)
      (44% difference, 95% CI 26-63%, p < 0.001) and for experienced laryngoscopists
      were 14/56 (25%) vs 47/56 (84%) (59% difference, 95% CI 42-72%, p < 0.0001),
      respectively. First-time oesophageal intubation rates for students were 15/23
      (65%) vs 3/23 (13%) (-52% difference, 95% CI -25 to -72%, p < 0.001) and for
      experienced practitioners 9/56 (16%) vs 0/56 (0%) (-16% difference, 95% CI -9 to 
      28%, p = 0.0014). Student paramedics and experienced prehospital laryngoscopists
      managing a manikin model of a grade III/IV view had increased first-time
      intubation rates and had lower rates of oesophageal intubation with the Airtraq
      compared with a standard laryngoscope.

PMID- 18086068
TI  - Assessment of manoeuvres required for successful blind tracheal intubation
      through the PAXpress.
AB  - A PAXpress (Vital Signs Inc., Barnham, UK) airway device was placed in 50 adult
      ASA grade I and II patients undergoing elective surgery under general
      anaesthesia. The alignment of the PAXpress to the larynx was scored
      fibreoptically. The patients were then intubated blindly through the PAXpress and
      the adjusting manoeuvres required for successful intubation and complications of
      intubation observed. Insertion of the PAXpress was successful in all patients,
      and intubation was successful in 42 (84%) patients. Eleven patients were
      intubated in the neutral position, seven with a flexion manoeuvre and 24 with an
      extension manoeuvre. Intubation was successful in 17/20, 18/20, 6/8 and 1/2 of
      patients with a fibreoptic alignment score of 1, 2, 3 and 4, respectively. When
      the fibreoptic alignment score was between 2 and 4 intubation was achieved
      predominantly with the extension manoeuvre (20/30, 66%) rather than the flexion
      manoeuvre (1/30, 3%) or the neutral position (5/30, 16%). Blood staining was
      observed in 20 patients. We conclude that blind tracheal intubation through
      PAXpress has a moderately good success rate and a high incidence of mucosal
      trauma. 'Extension' is the predominant adjusting manoeuvre required for blind
      tracheal intubation, especially when the alignment of the PAXpress to the larynx
      is poor.

PMID- 18086069
TI  - Accidental dural puncture and post dural puncture headache in obstetric
      anaesthesia: presentation and management: a 23-year survey in a district general
      hospital.
AB  - Post dural puncture headache can be a debilitating complication of epidural and
      subarachnoid anaesthesia for a new mother. In a survey of 18,337 epidurals and
      5021 subarachnoid blocks performed for obstetric procedures over a 23-year period
      in a district general hospital maternity unit, there were 167 recognised
      accidental dural punctures after epidurals (0.91%), with 147 patients (88%)
      developing post dural puncture headache. In addition there were 52 post dural
      puncture headaches after subarachnoid blocks (1.04%). Successful management of
      accidental dural puncture and post dural puncture headache requires adherence to
      clear policies and protocols, with close follow-up of patients by an experienced
      obstetric anaesthetist.

PMID- 18086070
TI  - Systematic review of the literature for the use of oesophageal Doppler monitor
      for fluid replacement in major abdominal surgery.
AB  - The use of intra-operative Doppler oesophageal probes provides continuous
      monitoring of cardiac output. This enables optimisation of intravascular volume
      and tissue perfusion in major abdominal surgery, which is thought to reduce
      postoperative complications and shorten hospital stay. Medline and EMBASE were
      searched using the standard methodology of the Cochrane collaboration for trials
      that compared oesophageal Doppler monitoring with conventional clinical
      parameters for fluid replacement in patients undergoing major elective abdominal
      surgery. Data from randomised controlled trials were entered and analysed in Meta
      view in Rev-Man 4.2 (Nordic, Denmark). We included five studies that recruited
      420 patients undergoing major abdominal surgery who were randomly allocated to
      receive either intravenous fluid treatment guided by monitoring ventricular
      filling using oesophageal Doppler monitor or fluid administration according to
      conventional parameters. Pooled analysis showed a reduced hospital stay in the
      intervention group. Overall, there were fewer complications and ICU admissions,
      and less requirement for inotropes in the intervention group. Return of normal
      gastro-intestinal function was also significantly faster in the intervention
      group. Oesophageal Doppler use for monitoring and optimisation of flow-related
      haemodynamic variables improves short-term outcome in patients undergoing major
      abdominal surgery.

PMID- 18086071
TI  - A peri-operative statin update for non-cardiac surgery. Part I: The effects of
      statin therapy on atherosclerotic disease and lessons learnt from statin therapy
      in medical (non-surgical) patients.
AB  - The utility of peri-operative statin therapy is currently considered to be
      inconclusive. To provide a platform for more meaningful peri-operative statin
      literature in the future, this is the first of two review articles evaluating
      peri-operative statin therapy. This review examines the predictors of
      cardiovascular outcome and therapeutic targets which are established in medical
      (non-surgical) patients. In patients with stable coronary artery disease at least
      4-6 weeks of standard statin therapy are required to realise most of the
      beneficial cellular and metabolic effects of statin therapy. Low-density
      lipoprotein-cholesterol reduction is associated with improved survival in these
      patients. In comparison, patients who sustain an acute coronary event require
      high-dose statin therapy probably initiated within 24 h with a therapeutic target
      of C-reactive protein reduction. Withdrawal of statin therapy results in a rapid
      return to endothelial dysfunction and amplification of the inflammatory process,
      which may increase cardiovascular risk.

PMID- 18086072
TI  - Minimum and optimum light requirements for laryngoscopy in paediatric
      anaesthesia: a manikin study.
AB  - Direct laryngoscopy is performed regularly in paediatric anaesthetic practice for
      the purpose of intubating a patient's trachea. A minimum illumination of 700 lux
      at a distance of 20 mm has been suggested in a draft standard for laryngoscopes
      from the International Organization for Standardization. We investigated the
      minimum and optimum illumination required by anaesthetists during laryngoscopy.
      Fifty anaesthetists were recruited to perform laryngoscopy on a child manikin
      with a selection of laryngoscope blades and bulbs attached to a variable voltage
      supply. There was a large variation in the illumination range of different bulb
      and blade combinations. We demonstrated a large interindividual variability
      between anaesthetists for illumination requirements during laryngoscopy.
      Anaesthetists can see the larynx at very low light levels, but optimum
      illumination was significantly greater than minimum illumination. Two of the six
      combinations could produce more than 700 lux. In all, 78% and 54% of
      anaesthetists considered 700 lux too bright with a halogen and xenon bulb,
      respectively. Our study suggests that the proposed standard of 700 lux may
      possibly be too bright.

PMID- 18086073
TI  - The effect of flow on the filtration performance of paediatric breathing system
      filters.
AB  - The effect of flow on the filtration performance of six different types of filter
      intended for use in paediatric anaesthesia was measured by challenging the
      filters with sodium chloride particles at five different flows: 6, 10, 15, 20 and
      30 l x min(-1). Twenty-five unused samples of each filter type were evaluated.
      The pressure drop across each filter was measured at the same flows as those used
      to measure penetration. The pressure drop varied both between and within the
      types of filter. Mean pressure drop varied between 89 and 262 Pa at a flow of 15
      l x min(-1) for the six different filters. Penetration of sodium chloride
      particles varied from 1.9 to 18% at 15 l x min(-1) for the six filters. Allowing
      for the variation in pressure drop, the penetration of particles increased fairly
      linearly as flow increased for all six filter types. The increase in penetration
      per unit increase in flow varied from 0.11 to 0.82% per litre per minute. Over
      the range of flows studied, the increase in penetration with flow is fairly
      predictable.

PMID- 18086074
TI  - The effect of volatile anaesthetic agents on the filtration performance of
      paediatric breathing system filters.
AB  - The aim of this study was to determine the filtration performance of five
      commonly used paediatric breathing system filters following exposure to
      desflurane, isoflurane and sevoflurane. It has been suggested that oil may
      degrade the performance of filter material. Volatile anaesthetic vapours are
      organic and hence may affect the filtration performance of breathing system
      filters during anaesthesia. This has not been tested for various concentrations
      of volatile agent, type and duration of exposure. The filtration performance of
      the filters was measured following exposure to desflurane, isoflurane and
      sevoflurane at 1 and 2 minimum alveolar concentration (MAC) for 1 and 4 h.
      Penetration of particles through the Clear-Therm Micro, Clear-Therm Mini and
      Humid-Vent Filter Pedi increased by between 2.4 and 2.8 times after exposure to
      desflurane at 2 MAC for 4 h compared to that through unexposed filters (p <
      0.0001 for all three filters). Further investigation is required to determine
      whether this reduction in filtration performance by desflurane is clinically
      significant.

PMID- 18086075
TI  - Randomised crossover comparison of the Ambu AuraOnce Laryngeal Mask with the LMA
      Classic laryngeal mask airway in paralysed anaesthetised patients.
AB  - We compared the performance of the Ambu AuraOnce Laryngeal Mask with that of the
      LMA Classic laryngeal mask airway during controlled anaesthesia. Forty patients
      requiring intermittent positive pressure ventilation were studied using a
      randomised crossover design. The mean (SD) oropharyngeal leak pressure for the
      Ambu device (19 (7.5) cmH2O) was significantly greater than for the LMA Classic
      (15 (5.2) cmH2O; p = 0.004), and the number of attempts for successful insertions
      was significantly less (39 (50%) vs 45 (56%), respectively; p = 0.02). There was
      one failure to obtain a patent airway with the Ambu Laryngeal Mask and none with
      the LMA Classic. Insertion of the Ambu Laryngeal Mask required more manipulations
      to achieve a patent airway than did the LMA Classic (6 (15%) vs 1 (2.5%),
      respectively; p = 0.045), but the time taken for insertion was similar between
      the two groups. The incidence of trauma, grade of fibreoptic view, peak airway
      pressure and quality of ventilation during maintenance of anaesthesia were
      similar in both groups.

PMID- 18086077
TI  - Acute liver failure following therapeutic paracetamol administration in patients
      with muscular dystrophies.
AB  - Clinically significant liver damage in patients taking therapeutic doses of
      paracetamol is very rare. We report two cases of fulminant hepatic failure caused
      by therapeutic (4 g x day(-1)) paracetamol administration on our Intensive Care
      Unit. Both patients had a muscular dystrophy and presented with a chest infection
      on a background of endstage neuromuscular respiratory failure. We also noted one
      further similar case in the literature and suggest a relationship between
      muscular dystrophy and paracetamol-induced hepatotoxicity. In this report we
      discuss in detail possible mechanisms that may account for this apparent
      association, which include altered pharmacokinetics, reduced glutathione stores,
      malnutrition and hypoxic injury.

PMID- 18086076
TI  - Phaeochromocytoma crisis--a rare indication for extracorporeal membrane
      oxygenation.
AB  - We report on a case of phaeochromocytoma whose initial presentation mimicked an
      acute myocardial infarction. Veno-arterial extracorporeal membrane oxygenation
      was used for the management of refractory cardiogenic shock and massive lung
      oedema. Suspicion and diagnosis of a phaeochromocytoma were made due to its
      unique clinical presentation during extracorporeal membrane oxygenation.
      Stabilisation of the crisis and recovery of cardiopulmonary function were
      achieved using the support of extracorporeal membrane oxygenation. This case
      highlights the difficulty in the differential diagnosis of cardiogenic shock
      secondary to phaeochromocytoma and the important role of extracorporeal membrane
      oxygenation can have in the successful resuscitation and management of these
      patients.

PMID- 18086078
TI  - Osmotic demyelination syndrome following rapid correction of hyponatraemia.
AB  - We report a case of a young male with adrenal hypoplasia who presented following
      water intoxication with severe hyponatraemia and seizures. He required a period
      of intensive care and over the initial 24 h his serum sodium corrected at average
      of 0.9 mmol x l(-1) h(-1). He subsequently developed osmotic demyelination
      syndrome. Following supportive treatment he made a full recovery. Severe
      hyponatraemia carries a risk of cerebral oedema with a significant mortality, yet
      correcting it too rapidly can result in osmotic demyelination syndrome, again
      with potentially disastrous consequences. It may be difficult to determine the
      duration and aetiology of the hyponatraemia and this is necessary to guide
      treatment. There is no consensus about the optimal rate of correction of
      hyponatraemia but formulae such as the Adrogue and Madias formula can be used to
      guide treatment with normal or hypertonic saline. Continuous veno-venous
      haemofiltration has been used effectively in this setting.

PMID- 18086079
TI  - 'Training for trauma'--the system has changed.

PMID- 18086080
TI  - The truth about trauma care.

PMID- 18086083
TI  - The concept of surgical operating list 'efficiency': a formula to describe the
      term.

PMID- 18086085
TI  - Reliability of the 'pop' sign as an indicator of dural puncture.

PMID- 18086086
TI  - Peri-operative considerations for Anderson-Fabry disease.

PMID- 18086087
TI  - Emergency anaesthesia at high altitude.

PMID- 18086088
TI  - Use of a plastic Yankauer sucker for the reinsertion of a displaced percutaneous
      dilational tracheostomy tube.

PMID- 18086089
TI  - Transfer device for supermorbidly obese patients.

PMID- 18086090
TI  - Calculating variable 'alpha' for predicting plasma concentrations of steady-state
      remifentanil.

PMID- 18086091
TI  - Positioning of the tracheal tube during surgical tracheostomy.

PMID- 18086092
TI  - Reducing the risk of air embolism following administration of intravenous
      paracetamol.

PMID- 18086093
TI  - Failure of Draeger Infinity pulse contour monitoring system when used with 8-cm
      PiCCO catheters.

PMID- 18086094
TI  - More leaky intravenous cannulae.

PMID- 18086096
TI  - More toothy matters.

PMID- 18086097
TI  - A gelatine-based ultrasound phantom.

PMID- 18086100
TI  - The effect of male circumcision on sexual satisfaction and function, results from
      a randomized trial of male circumcision for human immunodeficiency virus
      prevention, Rakai, Uganda.
AB  - OBJECTIVE: To investigate the relationship between adult male circumcision and
      sexual satisfaction and function in men, as observational studies on the effect
      of adult male circumcision on sexual satisfaction show conflicting results.
      SUBJECTS AND METHODS: We investigated self-reported sexual satisfaction and
      function among men enrolled in a randomized trial of male circumcision for human
      immunodeficiency virus (HIV) prevention conducted in Rakai, Uganda. In all, 4456
      sexually experienced HIV-negative males aged 15-49 years were enrolled; 2210 were
      randomized to receive immediate circumcision (intervention arm) and 2246 to
      circumcision delayed for 24 months (control arm). Men were followed up at 6, 12
      and 24 months, and information on sexual desire, satisfaction and erectile
      dysfunction was collected. These variables were compared between the study arms
      and over time within the study arms, using chi-square or Fisher's exact tests.
      The trial registration number is NCT00425984. RESULTS: There were no differences
      between the study arms at enrollment and problems with sexual satisfaction and
      function were reported by <2% of participants in both study arms at all time
      points. At 6 months, no difficulty with penetration was reported by 98.6% of
      circumcised men and 99.4% of controls (P = 0.02), and no pain on intercourse was
      reported by 99.4% circumcised and 98.8% of uncircumcised men (P = 0.05). There
      were no differences between the study arms in penetration or dyspareunia at later
      visits. Sexual satisfaction increased from 98.0% at enrollment to 99.9% at 2
      years among the controls (P < 0.001), but there was no trend in satisfaction
      among circumcised men (enrollment 98.5%, 2 years 98.4%, P = 0.8). CONCLUSION:
      Adult male circumcision does not adversely affect sexual satisfaction or
      clinically significant function in men.

PMID- 18086101
TI  - Scarless single port transumbilical nephrectomy and pyeloplasty: first clinical
      report.
AB  - OBJECTIVE: To report the initial clinical cases of scarless, single port,
      transumbilical nephrectomy and pyeloplasty. PATIENTS AND METHODS: One patient
      each underwent single port transumbilical nephrectomy and pyeloplasty using the R
      Port (Advanced Surgical Concepts), inserted through a transumbilical incision in
      both cases. Novel, specialized instruments, curved at the shaft, were used in
      addition to standard laparoscopic instrumentation. During pyeloplasty, a 2-mm
      needle-port (MiniSite, USSC, Norfolk, CT, USA) was also inserted, with no skin
      incision, to facilitate suturing. RESULTS: Both procedures were technically
      successful with no extra-umbilical skin incisions. The total operative duration
      was 3.4 and 2.7 h, the estimated blood loss 100 and 50 mL, and the hospital stay
      was 1 and 2 days for the nephrectomy and pyeloplasty, respectively. There were no
      complications during or after surgery. The total analgesia requirement was 100
      and 150 mg of keterolac, and visual analogue pain scores were 8/10 and 2/10 at 1
      and 2 days after surgery, respectively. CONCLUSIONS: Transumbilical, single port
      nephrectomy and pyeloplasty are technically feasible. The first initial clinical
      experience of organ-ablative and reconstructive renal surgery with this approach
      is reported.

PMID- 18086102
TI  - Re: A randomized controlled trial of topical glyceryl trinitrate before
      transrectal ultrasonography-guided biopsy of the prostate.

PMID- 18086103
TI  - Re: The increasing use of intravesical therapies for stage T1 bladder cancer
      coincides with decreasing survival after cystectomy.

PMID- 18086104
TI  - Factors leading to failure of the self-locking vascular clips: preliminary
      findings of the WPU-SIMISAD Group.

PMID- 18086105
TI  - Re: Treating patients with overactive bladder symptoms with antimuscarinics;
      heart rate considerations.

PMID- 18086107
TI  - Holmium laser enucleation of the prostate (HoLEP).

PMID- 18086108
TI  - Clinical features predicting the detection of abnormalities by double balloon
      endoscopy in patients with suspected small bowel bleeding.
AB  - BACKGROUND AND AIM: Although double balloon endoscopy (DBE) has demonstrated a
      high diagnostic yield in suspected small bowel bleeding, it is not known whether
      DBE is of equal value to all patients with suspected small bowel bleeding or of
      greater benefit in selected subgroups. We aimed to determine whether any clinical
      features predict an increased likelihood of finding a lesion in patients with
      suspected small bowel bleeding. METHODS: We retrospectively analyzed clinical
      features of 43 consecutive patients (M : F = 26:17, age 13-82 years) who
      underwent DBE because of suspected small bowel bleeding. Data associated with DBE
      procedure were collected prospectively. Predictive factors for the detection of a
      lesion were determined by comparison of clinical features between patients with
      positive DBE findings and those with negative findings. RESULTS: Potential
      bleeding sources were discovered in 30 patients (69.8%) out of 43. Duration of
      bleeding was longer in patients with positive DBE findings than in those with
      negative findings (195 +/- 311 vs 18 +/- 17 days, P = 0.015). Number of bleeding
      episodes was higher in patients with positive DBE findings (2.2 +/- 1.2 vs 1.3 +/
      0.5, P = 0.011). The odds ratio for the detection of bleeding focus on DBE for
      patients with two or more bleeding episodes, relative to those with only one
      current bleeding episode was 5.67 (95% CI: 1.12-28.81, P = 0.036) in multivariate
      analysis. CONCLUSION: DBE may be the most useful in patients with suspected small
      bowel bleeding if they have a history of frequent bleeding episodes over a long
      period.

PMID- 18086109
TI  - Prognostic models in cirrhotics admitted to intensive care units better predict
      outcome when assessed at 48 h after admission.
AB  - BACKGROUND AND AIM: The accuracy of prognostic models in critically ill
      cirrhotics at admission to intensive care units (ICU) may be unreliable.
      Predictive accuracy could be improved by evaluating changes over time, but this
      has not been published. The aim of the present study was to assess the
      performance of prognostic models in cirrhotics at admission (baseline) and at 48
      h to predict mortality in the ICU or within 6 weeks after discharge from the ICU.
      METHODS: One hundred and twenty-eight cirrhotics (77 males, mean age 49 +/- 11.3
      years) were consecutively admitted and alive 48 h after admission with 89% on
      mechanical ventilation, 76% on inotrope support, and 42% with renal failure.
      Prognostic models used were Child-Turcotte-Pugh (CTP), Model for End-stage Liver
      Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE) II,
      Sequential Organ Failure Assessment (SOFA), failing organ systems (FOS) at
      baseline and at 48 h, Deltascore (difference between baseline and at 48 h) and
      the mean score (MN - score admission + 48 h/2) which were compared by area under
      the receiver operating characteristic curves (AUC). RESULTS: Mortality was 54.7%
      (n = 70) due to multiple organ failure in 55%. CTP, MELD, APACHE II, SOFA and FOS
      performed better at 48 h (AUC: 0.78, 0.86, 0.78, 0.88 and 0.85, respectively)
      than at baseline (AUC: 0.75, 0.78, 0.75, 0.81 and 0.79, respectively). The mean
      score had better discrimination than the baseline score; the Deltascore had poor
      predictive ability (AUC < 0.70). SOFA score (48 h: 0.88, mean: 0.88) and FOS
      (mean: 0.88) had the best accuracy, with a SOFA and MN-SOFA > or = 10 predicting
      mortality in 93% and 91%, respectively, and MN-FOS > or = 1.5 in 98%.
      CONCLUSIONS: In cirrhotics, prognostic scores in the ICU at 48 h had better
      discrimination than baseline scores for short-term mortality. SOFA and FOS models
      had the best performance.

PMID- 18086110
TI  - Efficacy and safety of low-pressured and short-time dilation in endoscopic
      papillary balloon dilation for bile duct stone removal.
AB  - BACKGROUND AND AIM: Endoscopic papillary balloon dilation (EPBD) has been
      advocated as an alternative therapy to endoscopic sphincterotomy for bile duct
      stones. However, studies have shown that EPBD may increase the risk for
      pancreatitis. Pancreatitis after EPBD is believed to be related to papillary
      damage after balloon dilation. We changed the dilation method to a theoretically
      less hazardous one. This modified dilation method was compared with the initial
      method. METHODS: A total of 324 patients with bile duct stones underwent EPBD by
      the modified method between June 1999 and June 2003. Three hundred and twenty
      four patients undergoing EPBD by the initial method served as a historical
      control group. The success rate of stone removal and the incidence of procedure
      related pancreatitis were compared between the two groups. In the modified
      method, the balloon was inflated until disappearance of the balloon waist, and
      the pressure was then maintained for 15 s. In the initial method, the balloon was
      inflated at 8 atmospheres for 2 min. RESULTS: Bile duct stones were successfully
      removed in 313 of 324 patients (96.6%) in the modified group and in 314 of 324
      patients (96.9%) in the initial group (not significant). The incidence of post
      procedure pancreatitis showed a lower tendency in the modified group (4.0%,
      13/324) than in the initial group (7.4%, 24/324) (P-value = 0.0626). The severity
      of pancreatitis was significantly reduced in the modified group. CONCLUSION: The
      modified method of EPBD is feasible for extraction of bile duct stones, and may
      potentially decrease the incidence of severe post-EPBD pancreatitis.

PMID- 18086111
TI  - Importance of biliary excretion of indomethacin in gastrointestinal and hepatic
      injury.
AB  - BACKGROUND AND AIMS: A mechanism for protection of gastrointestinal (GI) and
      hepatic cells from damaging detergent actions of bile acids appears to involve
      the bile component, phosphatidylcholine (PC). Non-steroidal anti-inflammatory
      drugs (NSAIDs) induce intestinal injury in direct proportion to their ability to
      be excreted into bile, and are known to chemically associate with PC. We
      investigated the role of bile acids and PC in the mechanism of indomethacin
      induced epithelial injury. METHODS: Rats were injected orally or intravenously
      with radiolabeled indomethacin and their bile was collected over time for
      determination of NSAID secretion. Bile from rats treated with or without
      indomethacin was used in studies of red blood cell (RBC) hemolysis as a measure
      of membrane cytotoxicity. The bile salt, sodium deoxycholate (SDC), and
      indomethacin were tested alone and in combination with PC on RBC and on hepatic
      HepG2 cells. RESULTS: Intravenously or orally given indomethacin was
      quantitatively excreted (approximately 50%) into bile over a 2-h study period.
      Bile from a rat treated with indomethacin or bile with exogenous indomethacin was
      cytotoxic to RBC, and the injury was prevented by the addition of PC. Hepatocytes
      exposed to SDC showed injury that could be dose-dependently prevented by PC, and
      reversed by indomethacin. CONCLUSIONS: Biliary PC plays an important
      physiological role in protecting GI and hepatic epithelia from the cytotoxic
      actions of bile salts. The ability of NSAIDs excreted into the bile to associate
      with mixed bile salt micelles and reduce the protective action of the PC may be a
      critical component in the drugs' pathogenic mechanism.

PMID- 18086112
TI  - Erythropoietin promotes hepatic regeneration after extended liver resection in
      rats.
AB  - BACKGROUND AND AIM: It has been proven in various animal studies that recombinant
      human erythropoietin (rHuEPO) protects renal, cardiac and neuronal, as well as
      hepatic, tissue from ischemia, and promotes regeneration of adult central nervous
      system neurons. To date, no data are available as to whether rHuEPO has the
      ability to stimulate liver regeneration after liver resection. METHODS: Rats
      undergoing 70% or 90% hepatectomy received an intraportalvenous administration
      (i.p.) of rHuEPO prior to resection or a subcutaneous injection (s.c.) for 3 days
      postoperatively, control animals were treated with surgery and saline injection
      only. Regeneration capacity of remnant livers was studied over 7 days by
      histology and immunohistochemistry (Ki-67, proliferating cell nuclear antigen
      [PCNA]). Polymerase chain reaction was carried out to measure transforming growth
      factor beta (TGF-beta), hypoxia induced factor (HIF), signal transducing
      activator 3 and vascular endothelial growth factor. RESULTS: Ten-day survival in
      rats undergoing 90% hepatectomy significantly increased in i.p.-pretreated
      animals. After 70% hepatectomy the mitotic index was significantly increased in
      both rHuEPO-treated groups. These data were confirmed by PCNA and Ki-67
      expression, which was significantly increased in the treated groups 24 h and 2
      days after liver resection. TGF-beta and HIF mRNA both were upregulated in
      control animals 3 h after surgery. CONCLUSION: rHuEPO effectively increased liver
      regeneration in rats after 70% liver resection and enhanced survival after 90%
      hepatectomy. Thus, rHuEPO may increase the regenerative capacity after major
      hepatectomy.

PMID- 18086113
TI  - Microbiological monitoring of endoscopes: 5-year review.
AB  - Periodic microbiological monitoring of endoscopes is a recommendation of the
      Gastroenterological Society of Australia (GENSA). The aim of monitoring has been
      to provide quality assurance of the cleaning and disinfection of endoscopes;
      however, there is controversy regarding its frequency. This lack of consensus
      stimulated a review of the experience within our health service. At Southern
      Health, routine microbiological sampling has involved 4-weekly monitoring of
      bronchoscopes, duodenoscopes and automated flexible endoscope reprocessors
      (AFER), and 3-monthly monitoring of all other gastrointestinal endoscopes.
      Records of testing were reviewed from 1 January 2002 until 31 December 2006. A
      literature review was conducted, cost analysis performed and positive cultures
      investigated. There were 2374 screening tests performed during the 5-year period,
      including 287 AFER, 631 bronchoscopes for mycobacteria and 1456 endoscope
      bacterial screens. There were no positive results of the AFER or bronchoscopes
      for mycobacteria. Of the 1456 endoscopic bacterial samples, six were positive;
      however, retesting resulted in no growth. The overall cost of tests performed and
      cost in time for nursing staff to collect the samples was estimated at $AUD
      100,400. Periodic monitoring of endoscopes is both time-consuming and costly. Our
      review demonstrates that AFER (Soluscope) perform well in cleaning endoscopes.
      Based on our 5-year experience, assurance of quality for endoscopic use could be
      achieved through process control as opposed to product control. Maintenance of
      endoscopes and AFER should be in accordance with the manufacturer's instructions
      and microbiological testing performed on commissioning, annually and following
      repair. Initial prompt manual leak testing and manual cleaning followed by
      mechanical leak testing, cleaning and disinfection should be the minimum standard
      in reprocessing of endoscopes.

PMID- 18086114
TI  - Plasma lipid alterations after total splenectomy, subtotal splenectomy and
      splenic auto-implants in rats.
AB  - BACKGROUND AND AIM: The relation between the spleen and lipid metabolism has not
      been properly studied. In order to contribute to the filling of this gap, in the
      present investigation we experimentally assessed the lipidogram of rats in the
      presence of the spleen, in asplenia, and after conservative spleen surgeries.
      METHODS: Fifty female Wistar rats of similar weight and age were divided into
      five groups submitted to the following procedures: group 1: control, with an
      intact spleen; group 2: sham operation; group 3: total splenectomy; group 4:
      subtotal splenectomy; and group 5: total splenectomy complemented with autogenous
      spleen tissue implants. Four months after the interventions, serum triglycerides,
      total cholesterol and fractions (very-low-density lipoprotein [VLDL]-cholesterol,
      low-density lipoprotein [LDL]-cholesterol, high-density lipoprotein [HDL]
      cholesterol) were determined. The results for the four groups were compared by
      analysis of variance followed by the Tukey-Kramer test, with the level of
      significance set at P < 0.05. RESULTS: There were no differences between groups
      1, 2, 4 and 5. In the animals submitted to total splenectomy, total cholesterol
      (P = 0.0151) and LDL-cholesterol fraction concentrations (P < 0.0001) were
      higher, whereas HDL-cholesterol fraction concentrations were lower (P = 0.0026)
      than those detected in the other groups. There was no difference in triglycerides
      (P = 0.1571) or VLDL-cholesterol (P = 0.2527) between groups. CONCLUSION: The
      spleen probably plays an important role in the lipid metabolism of female rats
      and total splenectomy may be related to changes in cholesterol control. It is
      possible that preservation of spleen tissue prevents such metabolic disorders.

PMID- 18086115
TI  - Survival rates according to the Cancer of the Liver Italian Program scores of 345
      hepatocellular carcinoma patients after multimodality treatments during a 10-year
      period in a retrospective study.
AB  - BACKGROUND AND AIM: The Cancer of the Liver Italian Program (CLIP) score has been
      demonstrated to have superior prognostic ability in hepatocellular carcinoma
      (HCC) patients worldwide, but there has never been sufficient assessment of the
      efficacy of treatment modalities according to the CLIP score. This retrospective
      cohort study of HCC patients was conducted to assess the efficacy of treatment
      modalities according to the CLIP score. METHODS: We compared the efficacy of
      hepatic resection (HR) (n = 101), radiofrequency ablation with prior
      transcatheter arterial chemoembolization (RFA + TACE) (n = 115), percutaneous
      ethanol injection with prior TACE (PEI + TACE) (n = 43), and TACE (n = 86) as a
      primary treatment in terms of survival among 345 patients treated at Mie
      University Hospital between 1995 and 2004, according to CLIP score. RESULTS: The
      overall survival rates in the RFA + TACE group were significantly higher in the
      patients with CLIP scores of 1, 2, and 3 or more (5-year, 70.9%; 3-year, 73.7%;
      and 3-year, 100%, respectively), but they were not significantly different from
      the 5-year survival rates of the HR group with a CLIP score of 0 (83.7%). Among
      the patients with a CLIP score of 0, a significantly higher disease-free survival
      rate (5-year: 33.7%) was obtained in the HR subgroup (n = 35) than in the RFA +
      TACE subgroup (n = 35), both of which were followed since 2000, but morbidity
      (21.8%) was highest in the HR group. CONCLUSION: RFA + TACE is concluded to be a
      safe treatment modality with better overall survival (5-year, > 60%) in HCC
      patients regardless of their CLIP score.

PMID- 18086116
TI  - Does every short stature child need screening for celiac disease?
AB  - AIM: To study the etiological profile of short stature at a tertiary care
      hospital in north India. METHODS: In this prospective study, 176 children with
      short stature were enrolled from January 2005 to December 2006. Appropriate
      screening and definitive tests were performed to establish the etiology of short
      stature. RESULTS: Celiac disease (CD) emerged as the single most common (15.3%)
      cause of short stature, followed by various endocrine disorders. It was
      interesting to note that none of the CD patients presented with gastrointestinal
      symptoms. CONCLUSION: All short children should be screened for CD irrespective
      of gastrointestinal symptoms.

PMID- 18086117
TI  - Covered expandable nitinol stents for malignant gastroduodenal obstructions.
AB  - BACKGROUND AND AIM: The aim of the present study was to investigate the clinical
      effectiveness, safety, and outcome associated with the use of covered expandable
      Nitinol stents (Taewoong Medical, Seoul, Korea) for the treatment of malignant
      gastroduodenal obstructions. METHODS: Between March 2001 and October 2004,
      covered expandable Nitinol stents were placed in 68 consecutive patients under
      endoscopic and fluoroscopic guidance for the following reasons: gastric carcinoma
      (n = 49), recurrent carcinoma after partial gastrectomy (n = 7), or another
      malignant neoplasm involving the duodenum (n = 12). RESULTS: Technical success
      was achieved in 60 of the 68 patients (88.2%). After stent placement, mean
      dysphagia score improved from a mean of 3.5 to 1.2 (P < 0.001). The mean period
      of primary stent patency was 107.2 days. During follow up (mean 4.4 months;
      range, 1-15 months), major complications (migration [6], bleeding [3],
      perforation [1], ingrowth [1], overgrowth [7], fistula [1]) occurred in 19
      patients (27.9%), and stent migration occurred in six (8.8%) (proximal migration
      into the stomach [n = 3], or distal migration [n = 3]). Recurrent dysphagia
      (mainly due to tumor ingrowth/overgrowth) occurred in eight patients (11.8%).
      CONCLUSION: Covered expandable Nitinol stents appear to offer an effective and
      feasible palliative therapy in patients with a malignant gastroduodenal
      obstruction.

PMID- 18086118
TI  - Risk factors of lymph node metastasis in T1 esophageal squamous cell carcinoma.
AB  - BACKGROUND AND AIM: To perform endoscopic mucosal resection (EMR) for T1
      esophageal cancer, it is essential to estimate the lymph node status exactly. In
      order to evaluate the feasibility of EMR for esophageal cancers, we evaluated the
      clinicopathological features of T1 esophageal squamous carcinomas with an
      emphasis on the risk factors and distribution patterns of lymph node metastasis.
      METHODS: From 1994 to 2006, a total of 200 patients with T1 esophageal carcinoma
      were treated surgically in our institution. Among them, clinicopathological
      features were evaluated for 197 consecutive patients with T1 squamous cell
      carcinoma. RESULTS: The frequency of lymph node involvement was 6.25% (4/64) in
      mucosal cancers and 29.3% (39/133) in submucosal cancers (P < 0.001). In patients
      with M1 (n = 32) and M2 (n = 14) cancers, no lymph node metastasis was found. In
      multivariate analysis, size larger than 20 mm, endoscopically non-flat type, and
      endo-lymphatic invasion were significant independent risk factors for lymph node
      metastasis. The differentiation of tumor cell was not a risk factor for lymph
      node metastasis. CONCLUSIONS: We suggest that EMR may be attempted for flat
      superficial squamous esophageal cancers smaller than 20 mm. After EMR, careful
      histological examination is mandatory.

PMID- 18086119
TI  - Lifestyle risk factors for intrahepatic stone: findings from a case-control study
      in an endemic area, Taiwan.
AB  - BACKGROUND AND AIM: To examine associations between lifestyle risk factors and
      intrahepatic stone (IHS), we conducted a case-control study in Taiwan, which has
      the highest incidence of IHS in the world. METHODS: Study subjects were 151
      patients newly diagnosed with IHS at Chang Gung Memorial Hospital between January
      1999 and December 2001. Two control subjects per case were selected randomly from
      patients who underwent minor surgery at the same hospital and from family members
      or neighbors of the hospital staff. Controls were matched to each case by age and
      gender. Information on lifestyle factors was collected using a self-administered
      questionnaire. Strength of associations was assessed using odds ratios derived
      from conditional logistic models. RESULTS: Female patients were significantly
      shorter than female controls. Compared to subjects with two or fewer children,
      odds ratios for those with six or more children were 20.4 in men (95% confidence
      interval, 1.89-221) and 2.82 (0.97-8.22) in women. Increasing level of education
      lowered the risk of intrahepatic stone (trend P = 0.004 for men and < 0.0001 for
      women). Women who had consumed ground-surface water for a long period had a
      somewhat increased risk (trend P = 0.05). CONCLUSION: Lower socioeconomic status
      and poor hygiene may be involved in the development of intrahepatic stones.

PMID- 18086120
TI  - A prospective and comparative cohort study on efficacy and drug resistance during
      long-term lamivudine treatment for various stages of chronic hepatitis B and
      cirrhosis.
AB  - BACKGROUND AND AIMS: A prospective, non-randomized cohort study on long-term
      lamivudine treatment, comparing efficacy, drug resistance, and prognosis for
      various stages of chronic hepatitis B virus (HBV)-related liver disease was
      performed to elucidate the significance and indication of lamivudine for
      individual patients at each stage of disease. METHODS: A total of 158 cases
      consisting of 87 chronic hepatitis, 28 compensated cirrhosis, and 43
      decompensated cirrhosis, with serum HBV-DNA > 5 log(10) copies/mL and with
      elevated alanine aminotransferase (ALT) over twice the upper normal limit or
      complications of hepatic insufficiency, were administered 100 mg of lamivudine
      daily and monitored for HBV markers, biochemistry, and prognosis. RESULTS:
      Lamivudine reduced HBV-DNA and ALT equally in all groups. Serum albumin,
      prothrombin time (%), and platelet count increased in all groups. The increased
      margin of albumin was the highest in the decompensated cirrhosis and higher in
      the compensated cirrhosis than the chronic hepatitis groups. Cumulative incidence
      of virologic breakthrough was 16%, 42%, 49%, and 53% at 12, 24, 36, and 48
      months, respectively, and the strongest predictive factor for lamivudine
      resistance was persistent HBV-DNA at 3 months. Ascites, encephalopathy, and
      jaundice improved in the majority of patients with decompensated cirrhosis. On
      the other hand, hepatic failure developed or deteriorated in 10 patients after
      virologic breakthrough, and nine of them had decompensated cirrhosis.
      CONCLUSIONS: Lamivudine was effective in reducing HBV-DNA and improving hepatic
      reserve at all stages and was most beneficial and significant for decompensated
      cirrhosis. Meanwhile, close monitoring of viral load and immediate rescue
      treatment for lamivudine resistance is necessary to prevent hepatic failure in
      decompensated cirrhosis.

PMID- 18086121
TI  - Subepithelial mass lesions in the upper gastrointestinal tract.
AB  - The finding of a mass lesion in the upper gastrointestinal tract at endoscopy
      with apparent normal overlying mucosa is common. The differential diagnosis of
      such lesions is broad and includes those of intramural or extramural origin.
      Endoscopic ultrasound provides accurate imaging of subepithelial mass lesions and
      characterizes them according to size, echogenicity, and origin including the
      histologic layer if the lesion is intramural which narrows the differential
      diagnosis. Endoscopic ultrasound allows a guided tissue sample to be obtained for
      histologic confirmation which is especially important for hypoechoic lesions
      arising from the 3rd or 4th echogenic layers. The purpose of this article is to
      review the diagnosis of the more common subepithelial mass lesions with an
      emphasis on endoscopic ultrasound and the subsequent management or monitoring.

PMID- 18086122
TI  - Treatment outcomes of hepatic and pulmonary metastases from colorectal carcinoma.
AB  - BACKGROUND AND AIM: The resection of synchronous or metachronous pulmonary and
      liver metastasis is an aggressive treatment option for patients with stage IV
      colorectal cancer and has been shown to yield acceptable long-term survival. We
      reviewed our experience with colorectal cancer patients with both liver and lung
      resections to determine the efficacy of surgical resections. METHODS: We
      performed a single institution, retrospective analysis of all patients who
      underwent surgical hepatic and pulmonary resection for metastatic colorectal
      cancer between 1995 and 2004. RESULTS: A total of 32 patients underwent resection
      of both hepatic and pulmonary metastases secondary to colorectal cancer. The 5
      year overall survival from initial operation was 60.8%. The disease-free interval
      was 44.3 months (95% confidence interval: 24.7 and 63.8, respectively). Neither
      the number of pulmonary lesions nor the time interval between the primary surgery
      and the metastasectomy had a significant impact on survival (P = 0.134).
      CONCLUSION: An aggressive surgical treatment of selected colorectal cancer
      patients with lung and liver metastases resulted in prolonged survival. The 5
      year survival rate of 60.8% with no perioperative mortality was observed in our
      study.

PMID- 18086123
TI  - Attitudes, experiences, and interest in geriatrics of first-year allopathic and
      osteopathic medical students.
AB  - A cross-sectional survey was designed to assess interest in geriatric medicine of
      allopathic and osteopathic medical students and to determine whether their career
      interests were related to past experiences with and current attitudes toward
      older adults. The study was conducted at an allopathic and osteopathic medical
      school with 231 first-year medical students. Experiences with elderly people were
      measured using survey questions assessing amount and quality of experiences with
      grandparents, as well as experiences caring for, volunteering with, or having a
      paid position working with older adults. Attitudes were measured using the
      University of California at Los Angeles Geriatric Attitudes Scale, revised for
      applicability to medical students. Interest in geriatrics was measured using a 4
      point scale. Overall, students expressed positive attitudes toward older adults.
      Past experiences, including positive relationships with older relatives (P<.001)
      and experiences providing care for older adults (P<.001), were related to more
      positive attitude scores toward elderly people. Students had low interest in
      geriatric medicine, but those with more-positive attitudes were more likely to
      consider geriatrics as a career (odds ratio=8.18, P<.001). Furthermore, having
      prior experience caring for older persons increased interest in the field
      (P=.001). No significant differences were found between allopathic and
      osteopathic student interest in geriatrics or attitudes toward older adults.
      Efforts toward increasing the pool of future geriatricians and increasing
      positive attitudes toward older patients could be improved by providing quality
      experiences caring for and interacting with older adults before medical school
      training.

PMID- 18086124
TI  - Unhealthy drinking patterns in older adults: prevalence and associated
      characteristics.
AB  - OBJECTIVES: To examine the prevalence of unhealthy drinking patterns in community
      dwelling older adults and its association with sociodemographic and health
      characteristics. DESIGN: Cross-sectional analysis of nationally representative
      survey data. SETTING: The data source was the 2003 Access to Care file of the
      Medicare Current Beneficiary Survey, which represents the continuously enrolled
      Medicare population. PARTICIPANTS: Community-dwelling Medicare beneficiaries aged
      65 and older (N=12,413). MEASUREMENTS: The prevalence of unhealthy alcohol use by
      older adults defined in relation to two parameters of recommended limits: monthly
      use exceeding 30 drinks per typical month and "heavy episodic" drinking of four
      or more drinks in any single day during a typical month in the previous year.
      Sociodemographic and health status variables were also included. RESULTS: Nine
      percent of elderly Medicare beneficiaries reported unhealthy drinking, with
      higher prevalence in men (16%) than women (4%). In logistic regression analyses
      with the full sample, higher education and income; better health status; male
      sex; younger age; smoking; being white; and being divorced, separated, or single
      were associated with higher likelihood of unhealthy drinking. Among drinkers, in
      addition to sociodemographic variables, self-reported depressive symptoms were
      positively associated with unhealthy drinking. Among unhealthy drinkers, race and
      ethnicity variables were associated with likelihood of heavy episodic drinking.
      CONCLUSION: Almost one in 10 elderly Medicare beneficiaries report exceeding
      recommended drinking limits. Several distinct unhealthy drinking patterns were
      identified and associated with sociodemographic and health characteristics,
      suggesting the value of additional targeted approaches within the context of
      universal screening to reduce alcohol misuse by older adults.

PMID- 18086125
TI  - Soluble CD40L, platelet surface CD40L and total platelet CD40L in congestive
      heart failure: relationship to platelet volume, mass and granularity.
AB  - BACKGROUND: Many complications associated with congestive heart failure (CHF)
      have a thrombosis-related aetiology, which may involve platelets. The immune
      modulator pair CD40-CD40L has been proposed to be an important link between
      inflammation and thrombosis and may be important in the pathophysiology of CHF.
      OBJECTIVE: To study soluble CD40L (sCD40L), platelet surface CD40L (%GCD40L) and
      total platelet CD40L (pCD40L) levels in CHF patients, their relationships to
      other platelet indices (platelet volume, mass and component) and to assess their
      prognostic value. METHODS: We measured sCD40L (by ELISA); pCD40L (by a platelet
      lysate assay); platelet surface CD40L (%GCD40L) expression by flow cytometry;
      mean platelet volume (MPV), mean platelet mass (MPM) and mean platelet component
      (MPC); in 108 patients with stable CHF. Levels were compared with 37 'healthy
      controls' and 63 'disease controls'. After a median follow-up period of 490 days,
      clinical endpoints were determined. RESULTS: pCD40L was significantly higher in
      CHF than disease controls, but not sCD40L or %GCD40L levels. CHF patients and
      disease controls had higher MPV (one-way anova, P < 0.0001), whilst MPC was
      significantly lower in CHF patients (P < 0.0001), compared to healthy controls.
      All indices related to CD40L (i.e. sCD40L, pCD40L and %GCD40L) were neither
      related to disease severity or left ventricular ejection function, nor to
      clinical endpoints at follow-ups. CONCLUSION: Patients with stable CHF patients
      did not exhibit enhanced levels of CD40L and the latter did not predict clinical
      events at follow-up. The lack of difference in CD40L levels between CHF and
      disease controls suggests that CD40L may not have a major role in CHF per se, but
      in the comorbidities associated with CHF.

PMID- 18086126
TI  - Novel Brn3a cis-acting sequences mediate transcription of human trkA in neurons.
AB  - TrkA, the receptor tropomyosin-related kinase for nerve growth factor, is
      critical not only for the correct spatial and temporal development of sensory
      neurons during embryogenesis but also for the survival of sensory neurons, the
      differentiation and apoptosis of neuronal tumors and suppression of latent herpes
      simplex virus genomes. While the regulation of the expression of trkA is a
      complex process, the transcription factor Brn3a is known to play an important
      role as an enhancer of trkA transcription during development in the mouse.
      Despite considerable information on the regulation of trkA during embryogenesis,
      the mechanisms by which the expression of trkA is regulated in differentiated
      neurons, or the factors that influence its expression in tumor cells, have not
      been identified. We initiated studies to determine whether Brn3a/trkA promoter
      interactions may be important in a model of differentiated neurons and in
      medulloblastoma cells. We constructed a plasmid that contains 1043 base pairs of
      genomic sequences that extend to 30 nucleotides upstream of trkA coding region.
      In contrast to previous data, a short 190 bp region that lies proximal to the
      trkA initiation codon was sufficient for Brn3a responsiveness in Vero cells. This
      region was also sufficient for Brn3a trans-activation in nerve growth factor
      differentiated PC12 cells. At least two portions of the 190 bp fragment bind to
      Brn3a with an affinity high enough to be detected in electromobility shift
      assays. In addition, Brn3a increased levels of endogenous trkA transcripts in
      PC12 cells and initiated trkA expression in medulloblastoma cells, which normally
      do not express trkA.

PMID- 18086128
TI  - Characterization of folate uptake by choroid plexus epithelial cells in a rat
      primary culture model.
AB  - Reduced derivatives of folic acid (folates) play a critical role in the
      development, function and repair of the CNS. However, the molecular systems
      regulating folate uptake and homeostasis in the central nervous system remain
      incompletely defined. Choroid plexus epithelial cells express high levels of
      folate receptor alpha (FRalpha) suggesting that the choroid plays an important
      role in CNS folate trafficking and maintenance of CSF folate levels. We have
      characterized 5-methyltetrahydrofolate (5-MTHF) uptake and metabolism by primary
      rat choroid plexus epithelial cells in vitro. Two distinct processes are
      apparent; one that is FRalpha dependent and one that is independent of the
      receptor. FRalpha binds 5-MTHF with high affinity and facilitates efficient
      uptake of 5-MTHF at low extracellular folate concentrations; a lower affinity
      FRalpha independent system accounts for increased folate uptake at higher
      concentrations. Cellular metabolism of 5-MTHF depends on the route of folate
      entry into the cell. 5-MTHF taken up via a non-FRalpha -mediated process is
      rapidly metabolized to folylpolyglutamates, whereas 5-MTHF that accumulates via
      FRalpha remains non-metabolized, supporting the hypothesis that FRalpha may be
      part of a pathway for transcellular movement of the vitamin. The proton-coupled
      folate transporter, proton-coupled folate transporter (PCFT), mRNA was also shown
      to be expressed in choroid plexus epithelial cells. This is consistent with the
      role we have proposed for proton-coupled folate transporter in FRalpha-mediated
      transport as the mechanism of export of folates from the endocytic compartment
      containing FRalpha.

PMID- 18086127
TI  - Brain-derived neurotrophic factor over-expression in the forebrain ameliorates
      Huntington's disease phenotypes in mice.
AB  - Huntington's disease (HD), a dominantly inherited neurodegenerative disorder
      characterized by relatively selective degeneration of striatal neurons, is caused
      by an expanded polyglutamine tract of the huntingtin (htt) protein. The htt
      mutation reduces levels of brain-derived neurotrophic factor (BDNF) in the
      striatum, likely by inhibiting cortical BDNF gene expression and anterograde
      transport of BDNF from cortex to striatum. However, roles of the BDNF reduction
      in HD pathogenesis have not been established conclusively. We reasoned that
      increasing striatal BDNF through over-expression would slow progression of the
      disease if BDNF reduction plays a pivotal role in HD pathogenesis. We employed a
      Bdnf transgene driven by the promoter for the alpha subunit of Ca(2+)/calmodulin
      dependent kinase II to over-express BDNF in the forebrain of R6/1 mice which
      express a fragment of mutant htt with a 116-glutamine tract. The Bdnf transgene
      increased BDNF levels and TrkB signaling activity in the striatum, ameliorated
      motor dysfunction, and reversed brain weight loss in R6/1 mice. Furthermore, it
      normalized DARPP-32 expression of the 32 kDa dopamine and cAMP-regulated
      phosphoprotein, increased the number of enkephalin-containing boutons, and
      reduced formation of neuronal intranuclear inclusions in the striatum of R6/1
      mice. These results demonstrate crucial roles of reduced striatal BDNF in HD
      pathogenesis and suggest potential therapeutic values of BDNF to HD.

PMID- 18086130
TI  - In vitro culture of peri-gastrulation embryos of a macropodid marsupial.
AB  - Peri-gastrulation stage tammar wallaby embryos were cultured for up to 78 h in
      either Dulbecco's Modified Eagle's Medium or Medium 199, in air/6% CO(2) or 95%
      O(2)/5% CO(2), and with added fetal calf or wallaby serum. There was little
      difference between the two media or sera sources, but development was markedly
      superior for embryos cultured in 95% O(2)/5% CO(2). Many embryos survived even
      prolonged culture periods up to and over 70 h, and although development continued
      throughout the culture period, the embryos as a whole became increasingly
      abnormal. Embryos explanted at the primitive streak/ regressing node stages
      performed better in vitro than embryos explanted at earlier or later stages. The
      embryo that developed the furthest had a newly formed node at the initiation of
      culture and after 64 h in vitro it had developed forelimb ridges, fused, beating
      heart tubes and mesonephric ducts. Thus high oxygen appears to be the critical
      component of the culture system for optimal development of primitive streak stage
      tammar embryos. These results provide a basis for developing culture conditions
      for longer term development of marsupial embryos in vitro.

PMID- 18086129
TI  - Hind limb scaling of kangaroos and wallabies (superfamily Macropodoidea):
      implications for hopping performance, safety factor and elastic savings.
AB  - The aim of this study was to examine hind limb scaling of the musculoskeletal
      system in the Macropodoidea, the superfamily containing wallabies and kangaroos,
      to re-examine the effect of size on the locomotor mechanics and physiology of
      marsupial hopping. Morphometric musculoskeletal analyses were conducted of 15
      species and skeletal specimens of 21 species spanning a size range from 0.8 to 80
      kg that included representatives of 12 of the 16 extant genera of macropodoids.
      We found that unlike other groups, macropodoids are able to match force demands
      associated with increasing body size primarily through a combination of positive
      allometry in muscle area and muscle moment arms. Isometric scaling of primary
      hind limb bones suggests, however, that larger species experience relatively
      greater bone stresses. Muscle to tendon area ratios of the ankle extensors scale
      with strong positive allometry, indicating that peak tendon stresses also
      increase with increasing body size but to a lesser degree than previously
      reported. Consistent with previous morphological and experimental studies, large
      macropodoids are therefore better suited for elastic strain energy recovery but
      operate at lower safety factors, which likely poses an upper limit to body size.
      Scaling patterns for extant macropodoids suggest that extinct giant kangaroos
      (approximately 250 kg) were likely limited in locomotor capacity.

PMID- 18086131
TI  - A novel simple technique for en face endothelial observations using water-soluble
      media -'thinned-wall' preparations.
AB  - A new, easily applicable technique providing en face preparations for light
      microscopy observations of the rat aorta and human thin wall arteries is
      described here. The major steps of the technique include attachment of the fixed
      and flattened vessel with the endothelium face down on a glass slide, covered
      with a water-soluble adhesive medium; drying and softening the vessel wall with
      another water-soluble medium; removal of the adventitia and most of the media;
      detaching the layer by placing the glass slide in water; and final attachment of
      the layer with the endothelium upwards. On such 'thinned-wall' preparations, 40
      50 microm in thickness, the stained endothelial cells are clearly visible.
      Because of the preparation thickness and the use of water-soluble media during
      the preparation, some subendothelial lipid accumulations, characteristic of the
      early stages of atherosclerosis process, are well preserved.

PMID- 18086132
TI  - Contrast-induced nephropathy.
AB  - Radiological procedures utilizing intravascular iodinated contrast media are
      being widely applied for both diagnostic and therapeutic purposes and represent
      one of the main causes of contrast-induced nephropathy (CIN) and hospital
      acquired renal failure. Due to the lack of any effective treatment, prevention of
      this iatrogenic disease, which is associated with significant in-hospital and
      long-term morbidity and mortality and increased costs, is the key strategy.
      However, prevention of CIN continues to elude clinicians and is a major concern
      during percutaneous coronary interventions (PCI), as patients undergoing these
      procedures often have multiple comorbidities. The purpose of this article is to
      examine the pathophysiology, risk factors, and clinical course of CIN, as well as
      the most recent studies dealing with its prevention and potential therapeutic
      interventions, especially during PCI.

PMID- 18086133
TI  - Management of multivessel coronary disease after ST elevation myocardial
      infarction treated by primary angioplasty.
AB  - BACKGROUND: Optimal treatment strategy of patients with ST elevation myocardial
      infarction (STEMI) and multivessel coronary artery disease (CAD) undergoing
      primary angioplasty is still unclear. Percutaneous coronary intervention (PCI) of
      non-culprit vessels simultaneously or soon after primary angioplasty is feasible
      and safe, but available data failed to consistently show a benefit in long-term
      clinical outcomes. METHODS: We retrospectively compared in-hospital and long-term
      outcomes for patients with STEMI and multivessel CAD treated by primary
      angioplasty with (Group 1, n=64) or without (Group 2, n=46) early, staged PCI of
      other angiographically significant coronary lesions. In-hospital major adverse
      cardiovascular events (MACE) were defined as a composite of death, periprocedural
      myocardial infarction after staged, elective PCI, stroke, stent thrombosis, major
      bleeding, and vascular complications. MACE at follow-up were defined as a
      composite of death, stroke, stent thrombosis, any coronary revascularization, and
      re-hospitalization for acute coronary syndrome. RESULTS: Group 1 patients
      underwent staged PCI 5.9 +/- 3.5 days after primary angioplasty. The mean length
      of follow-up was 13 months (392 +/- 236 days). The incidence of in-hospital MACE
      was 20.3% in Group 1 and 10.8% in Group 2 (P=0.186); the incidence of out of
      hospital MACE was 9.3% in Group 1 and 23.9% in Group 2 (P=0.037). In Group 1 in
      hospital MACE were driven by periprocedural myocardial infarction after the
      elective procedure, which occurred in 15.6% of patients. CONCLUSIONS: Our data
      show that multivessel, staged PCI in STEMI patients is associated with a low
      incidence of adverse events at follow-up but with a higher incidence of in
      hospital MACE, mainly driven by periprocedural myocardial infarction during the
      elective procedure.

PMID- 18086134
TI  - Transcatheter cardiac fistula repair with the Amplatzer Duct Occluder: a case
      report and review.
AB  - BACKGROUND: Clinically significant cardiac fistulas occur rarely and
      traditionally are surgically repaired. We describe the first known case of
      percutaneous closure of a left ventricular outflow tract (LVOT) to left atrium
      (LA) fistula formed as the result of aortic valve replacement surgery. CASE
      REPORT: The patient was an 86-year-old woman with a history of aortic valve
      replacement who began complaining of shortness of breath 7 years later. Initially
      she was misdiagnosed as having mitral regurgitation. However, a transesophageal
      echocardiography (TEE) showed the presence of a 7.5 mm fistula between her LVOT
      and LA, producing a large regurgitant jet. As she was not a good surgical
      candidate, she underwent percutaneous closure. An Amplatzer Duct Occluder 9-PDA
      006 (10 mm x 8 mm) device was successfully deployed in the fistula using TEE
      guidance. On follow-up, the patient described marked improvement of her symptoms.
      DISCUSSION: In the rare case of cardiac fistulas that are deemed high risk for
      surgical intervention, a percutaneous approach with an occlusive device offers
      promise in treating these patients.

PMID- 18086135
TI  - Fenestrated occluders for treatment of ASD in elderly patients with pulmonary
      hypertension and/or right heart failure.
AB  - Atrial septal defect (ASD) occlusion in adult patients with advanced age and left
      or right heart diastolic or systolic heart failure and in patients with pulmonary
      arterial hypertension bears a considerable risk of deterioration of heart
      failure. Therefore, we conducted this feasibility trial in 15 ASD patients with
      pulmonary hypertension and/or right heart failure using a fenestrated Amplatzer
      septal occluder (AGA Medical Corporation, Golden Valley, MN), allowing an
      overflow of blood in both directions in case of univentricular diastolic or
      systolic heart failure. In all patients, the device could be implanted without
      complications. All symptomatic patients showed an improvement in the New York
      Heart Association (NYHA) class, and no right or left heart decompensation
      occurred. On echocardiography, right ventricular end diastolic dimension (RVEDD)
      and pulmonary artery pressure (PAP) decreased significantly, whereas left
      ventricular end diastolic dimension (LVEDD) increased. Our series of 15 patients
      with fenestrated ASD occlusion shows that high-risk ASD occlusion can safely be
      accomplished with excellent clinical results and without complications by a
      fenestrated occluder.

PMID- 18086137
TI  - Ulnar artery as access site for cardiac catheterization: anatomical
      considerations.
AB  - Transradial approach to coronary angiography and angioplasty has been widely
      accepted in the last few years. As an alternative approach from the forearm, with
      some potential advantages, we decided to test the transulnar approach as a first
      choice strategy. METHODS AND RESULTS: Transulnar approach was tried in 131
      patients. In 29 patients there was no palpable ulnar artery or Allen test was
      negative. From the remaining 92 patients we performed successful coronary
      angiography and angioplasties in 59 patients (64% success rate in those who had
      palpable artery). The most frequent reason for access site failure (54.5% of all
      failed procedures) was inability to introduce wire despite good arterial flow. We
      found that the ulnar artery was not the largest artery of the forearm (mean
      diameter 2.76 +/- 0.08 mm compared with radial artery 3.11 +/- 0.12 mm) and had
      relatively frequent anatomical anomalies-11.9%. There were no major local
      complications, with very few minor complications. Spasm frequency was 13.6%,
      which is higher than that reported for transradial studies. CONCLUSIONS:
      Transulnar artery approach is feasible for cardiac catheterization: however, it
      has higher access site failure rates in an unselected patient population. It
      could be used as an alternative option in selected patients, but operators must
      be prepared to overcome frequent anatomical anomalies and spasm.

PMID- 18086136
TI  - Short-term effects of biocorrodible iron stents in porcine coronary arteries.
AB  - BACKGROUND: Biocorrodible iron stents carry the potential to overcome
      limitations, such as chronic inflammation and premature recoil, posed by
      biodegradable polymer and magnesium alloy stents. This study aimed to test the
      safety and efficacy of biocorrodible iron stents in porcine coronary arteries.
      METHODS: Iron stents and cobalt chromium stents were randomly deployed in the
      coronary arteries of juvenile domestic pigs. Animals were sacrificed at 28 days,
      and the vessels were fixed and processed for histochemistry. RESULTS: At 28 days,
      iron stents started to show signs of degradation without evidence of stent
      particle embolization or thrombosis without traces of excess inflammation, or
      fibrin deposition. At 28 days, the surface of the iron stent struts was black to
      brown and the vascular wall adjacent to the iron stent had a brownish tinge.
      There were no statistically significant differences in any of the measured
      parameters between segments implanted with iron and cobalt chromium stents. There
      were also no adverse effects in the persistent areas. CONCLUSION: The current
      study demonstrates that stents made of biocorrodible iron are safe. In some of
      the measured parameters, such as intimal thickness, intimal area, and percentage
      occlusion, there was a trend in favor of the iron stents.

PMID- 18086138
TI  - Systematic clinical evaluation and correction procedures for support of removable
      partial dentures.
AB  - Support, retention, and bracing are the three main functions of a direct retainer
      in removable partial dentures (RPDs). RPDs must have sufficient supporting
      ability for proper occlusal rehabilitation. Support ability depends on the fit,
      size, shape, and location of the occlusal rest. Support cannot be adjusted
      chairside in most cases. The purpose of this article is to present systematic
      evaluation criteria for support in an RPD and to describe methods for adjusting
      cast clasps with improper support. Appropriate design of RPDs and preparation of
      abutments are also described.

PMID- 18086139
TI  - Flexural strength, elastic modulus, and pH profile of self-etch resin luting
      cements.
AB  - PURPOSE: To determine the flexural strength, modulus of elasticity, and 24-hour
      pH profile of three self-etching resin luting cements and to obtain comparative
      data for representative conventional resin and resin-modified glass ionomer
      luting cements. MATERIALS AND METHODS: Three self-etching resin luting cements
      [RelyX Unicem (3M ESPE), Maxcem (Kerr), Embrace Wetbond (Pulpdent)] were tested
      and compared with two conventional resin cements [RelyX ARC (3M ESPE), Linkmax
      (GC)] plus two resin-modified glass ionomer luting cements [Fuji Plus (GC), RelyX
      Luting Plus (3M ESPE)]. Flexural strength and modulus of elasticity were
      determined using bar-shaped specimens (2 x 2 x 25 mm(3)) at 24 hours, using an
      Instron universal testing machine. Setting pH was measured using a flat-surface
      pH electrode at 0, 2, 5, 15, and 30 minutes and 1, 2, 4, 6, and 24 hours after
      mixing. Testing was performed under both dual-cured and self-cured conditions for
      all dual-cure cements. Data analysis included ANOVA and Tukey's test (p < 0.05).
      RESULTS: The self-etching cements showed similar flexural strength to the
      conventional resin cements, except for Embrace Wetbond self-cured, which was
      considerably lower. Modulus of elasticity results were both higher and lower than
      for conventional resin cements. All photopolymerized conventional and self-etch
      dual-cure cements showed markedly higher flexural strength and modulus than when
      solely self-cured. The resin-modified glass ionomer cements were characterized by
      lower flexural strength and elastic modulus. Self-etching resin cements showed
      lower initial pH (2.0 to 2.4) than conventional resin cements (4.8 to 5.2) and a
      wide range of final pH values (3.9 to 7.3) at 24 hours. One self-etching cement
      (Unicem) revealed a unique pH profile characterized by a more rapid rise in pH to
      neutrality both when dual-cured (15 minutes) and when auto-cured (1 hour).
      CONCLUSIONS: The self-etching resin cements evaluated in this study displayed
      disparate properties and cannot be considered a homogeneous group. Flexural
      strength properties were most uniform and were similar to those of the
      conventional resin cements, whereas moduli of elasticity showed greater
      variation. Setting pH profiles differed, depending on the brand and mode of cure,
      even within the same category of luting cement. All cements with dual-cure
      capability, both conventional and self-etch, showed significantly superior
      properties when photopolymerized.

PMID- 18086140
TI  - Effect of different exposure times on microwave irradiation on the disinfection
      of a hard chairside reline resin.
AB  - PURPOSE: This study evaluated the effectiveness of different exposure times of
      microwave irradiation on the disinfection of a hard chairside reline resin.
      MATERIALS AND METHODS: Sterile specimens were individually inoculated with one of
      the tested microorganisms (Pseudomonas aeruginosa, Staphylococcus aureus, Candida
      albicans, and Bacillus subtilis) and incubated for 24 hours at 37 degrees C. For
      each microorganism, 10 specimens were not microwaved (control), and 50 specimens
      were microwaved. Control specimens were individually immersed in sterile saline,
      and replicate aliquots of serial dilutions were plated on selective media
      appropriate for each organism. Irradiated specimens were immersed in water and
      microwaved at 650 W for 1, 2, 3, 4, or 5 minutes before serial dilutions and
      platings. After 48 hours of incubation, colonies on plates were counted.
      Irradiated specimens were also incubated for 7 days. Some specimens were prepared
      for scanning electron microscopic (SEM) analysis. RESULTS: Specimens irradiated
      for 3, 4, and 5 minutes showed sterilization. After 2 minutes of irradiation,
      specimens inoculated with C. albicans were sterilized, whereas those inoculated
      with bacteria were disinfected. One minute of irradiation resulted in growth of
      all microorganisms. SEM examination indicated alteration in cell morphology of
      sterilized specimens. The effectiveness of microwave irradiation was improved as
      the exposure time increased. CONCLUSION: This study suggests that 3 minutes of
      microwave irradiation can be used for acrylic resin sterilization, thus
      preventing cross-contamination.

PMID- 18086141
TI  - Fracture force, deflection, and toughness of acrylic denture repairs involving
      glass fiber reinforcement.
AB  - PURPOSE: Fractures in acrylic resin dentures occur quite often in the practice of
      prosthodontics. A durable repairing system for denture base fracture is desired
      to avoid recurrent fracture. The purpose of this study was to evaluate the
      fracture force, deflection, and toughness of a heat-polymerized denture base
      resin repaired with autopolymerized resin alone (C), visible light-polymerizing
      resin (VLC), or autopolymerizing resin reinforced with unidirectional (Stick) (MA
      FS) and woven glass fibers (StickNet) (MA-SN). Another group was repaired with
      autopolymerized resin after wetting the repair site with methyl methacrylate (MA
      MMA) for 180 seconds. A group of intact specimens was used as control. MATERIALS
      AND METHODS: Heat-polymerizing acrylic resin was used to fabricate the specimens.
      The specimens (10 per group) were sectioned in half, reassembled with a 3-mm butt
      joint gap, and repaired. A cavity was included when glass fibers were used. Three
      point bending was used to test the repaired site, and data were analyzed with one
      way ANOVA and the Tukey's post hoc test (alpha < or = 0.05). RESULTS: Fracture
      force, deflection, and toughness for the repaired groups without reinforcement
      (MA: 46.7 +/- 8.6 N, 2.6 +/- 0.3 mm, 0.08 +/- 0.001 J; MA-MMA: 41.0 +/- 7.2 N,
      2.7 +/- 0.4 mm, 0.07 +/- 0.002 J) were significantly lower (p < 0.05) than the
      control group (C: 78.6 +/- 9.6 N, 5.9 +/- 0.4 mm, 0.27 +/- 0.003 J). Repair with
      visible light-polymerizing resin (VLC, 15.0 +/- 4.0 N, 1.2 +/- 0.4 mm, 0.02 +/-
      0.0001 J) resulted in significant reduction of mechanical properties (p < 0.05).
      Reinforcement with glass fibers restored (MA-SN: 75.8 +/- 9.2 N) or increased (MA
      FS: 124.4 +/- 12.5 N) the original strength. CONCLUSION: The most effective
      repair method was the use of autopolymerized resin reinforced with unidirectional
      glass fibers.

PMID- 18086142
TI  - A comparison of the retention of three endodontic dowel systems following
      different surface treatments.
AB  - PURPOSE: Practitioners have several options during the selection of a dowel for
      core restoration, including metal and glass fiber materials. Retention of the
      cemented dowel is critical for the success of this type of restoration. The
      purpose of this in vitro study was to evaluate the effect of two surface
      treatments on the retention of three types of dowels placed into prepared canals
      with a resin cement. MATERIALS AND METHODS: Following the removal of the clinical
      crown, gutta percha was used to restore canals prepared to size 40 in 90
      extracted human anterior teeth. The access openings were then sealed, and the
      teeth stored in water for 3 weeks at 37 degrees C. Post preparations were made to
      a depth of 9 mm, and parallel ParaPost, FibreKleer, and FibreKor dowels were each
      used to restore 30 teeth. Ten dowels in each group received no surface roughening
      treatment, 10 were air abraded with 50 mu aluminum oxide, and 10 were air abraded
      with CoJet. The specimens were stored in water for 24 hours at 37 degrees C
      following dowel placement and prior to debonding with an Instron Testing Machine.
      RESULTS: The forces (N) required in tensile load to dislodge the dowels for each
      group were: ParaPost/CoJet 214.04 +/- 91.72, FibreKleer/AlOxide 196.07 +/- 57.69,
      ParaPost/AlOxide 184.46 +/- 35.05, FibreKleer/CoJet 176.36 +/- 42.43,
      FibreKor/AlOxide 174.32 +/- 53.64, ParaPost/Unroughened 174.14 +/- 40.74,
      FibreKor/CoJet 167.16 +/- 35.94, FibreKor/Unroughened 116.69 +/- 37.01, and
      FibreKleer/Unroughened 96.88 +/- 33.45. Post hoc analysis demonstrated that the
      unroughened FibreKor and FibreKleer dowels had significantly less retention than
      all other test groups (p < or = 0.05). CONCLUSION: Surface roughening with air
      abrasion increases retention in dowels cemented with a resin cement. Both the
      aluminum oxide and CoJet systems were equally effective in this regard.

PMID- 18086143
TI  - Effect of polishing technique and brushing on surface roughness of acrylic
      resins.
AB  - PURPOSE: This study evaluated the abrasion resistance of acrylic resin to routine
      dental brushing procedures using different dentifrices after the resin surface
      had been chemically or mechanically polished. MATERIALS AND METHODS: Eighty
      specimens were prepared using heat-polymerizing (HP) and autopolymerizing (AP)
      acrylic resin, and immediately submitted to grinding with abrasive stones and
      disks. The specimens were divided into two groups: the first group was
      mechanically polished (MP) using pumice slurry, and the second group was
      chemically polished (CP) using heated monomer. After polishing, the specimens
      were submitted to 30,000 brushing cycles. Surface roughness was measured after
      polishing and brushing procedures, using a Surfcorder SE 1700 rugosimeter. Data
      were statistically analyzed by ANOVA (alpha= 0.05). RESULTS: There were
      significant differences in surface roughness between polishing with MP and CP (p
      < 0.05). Significant differences in surface roughness were also found between
      brushing with MFP dentifrice and Tartar Control dentifrice (p < 0.05).
      CONCLUSION: MP produced smoother surfaces than CP, and surface roughness as a
      result of polishing technique was not influenced by acrylic resin type. Even
      though MP resulted in smoother surfaces initially, subjecting the acrylic resin
      to dentifrice brushing negated this advantage.

PMID- 18086144
TI  - Shaken baby syndrome in New Zealand, 2000-2002.
AB  - AIM: To describe the epidemiology of subdural haemorrhage (SDH) in New Zealand
      infants. METHODS: Prospective enrollment of all cases of infantile SDH from 2000
      to 2002. Retrospective analysis of national discharge and death data for the same
      period. RESULTS: Seventy-seven cases of infantile SDH were identified
      prospectively, and a further 49 cases retrospectively. Of these 126 cases, 92
      resulted from non-birth-related trauma. Forty-eight of these were attributed to
      abuse and 28 to accidental injury. Sixteen cases were undetermined. The 'minimum'
      annual incidence of inflicted infantile SDH in New Zealand is 14.7 per 100,000
      (95% confidence interval(CI) 10.8-19.4), and the 'maximum' 19.6 per 100,000 (95%
      CI 15.1-25.0). Among Maori, the 'minimum' is 32.5 per 100,000 (95% CI 21.4-47.3),
      and the 'maximum' 38.5 per 100,000 (95% CI 26.3-54.4). CONCLUSIONS: The
      epidemiology of infantile subdural haemorrhage in New Zealand is similar to that
      described elsewhere. Non-accidental head injury is a significant child health
      issue in New Zealand, and the incidence is particularly high among Maori.

PMID- 18086145
TI  - Local osteoprotegerin gene transfer to periodontal tissue inhibits
      lipopolysaccharide-induced alveolar bone resorption.
AB  - BACKGROUND AND OBJECTIVE: Osteoclastogenesis is primarily activated by receptor
      activator of nuclear factor kappaB ligand (RANKL) and is inhibited by
      osteoprotegerin (OPG). A previous study demonstrated that local OPG gene transfer
      to periodontal tissue inhibited RANKL-mediated osteoclastogenesis and
      experimental tooth movement. In the present study, we tested the hypothesis that
      local OPG gene transfer to the periodontium can neutralize RANKL activity induced
      by lipopolysaccharide injection, thereby inhibiting osteoclastogenesis and
      diminishing alveolar bone resorption in experimental periodontal disease.
      MATERIAL AND METHODS: Seven-week-old male Wistar rats received an injection of
      lipopolysaccharide or phosphate-buffered saline in the palatal gingiva of the
      upper first molars on both the right and left sides. An inactivated
      haemagglutinating virus of Japan (HVJ) envelope vector containing a mouse OPG
      expression plasmid [pcDNA3.1(+)-mOPG] or mock vector was injected periodically
      into the palatal periodontal tissue of the upper first molars. RESULTS:
      Lipopolysaccharide injection induced severe periodontal bone resorption. Local
      OPG gene transfer induced OPG production, and osteoclastogenesis was inhibited.
      Local OPG gene transfer significantly decreased alveolar bone resorption.
      CONCLUSION: Osteoprotegerin gene transfer to periodontal tissue inhibited
      osteoclastogenesis and alveolar bone resorption in lipopolysaccharide-induced
      experimental periodontal disease.

PMID- 18086146
TI  - Day/night differences in stress-induced gastric lesions in rats with an intact
      pineal gland or after pinealectomy.
AB  - The formation of acute gastric lesions depends upon the balance between the
      aggressive factors promoting mucosal damage and the natural defense mechanisms.
      Previous studies have shown that melatonin inhibits gastric acid secretion,
      enhances the release of gastrin, augments gastric blood flow (GBF), increases the
      cyclooxygenase-2 (COX-2)-prostaglandin (PG) system and scavenges free radicals,
      resulting in the prevention of stress-induced gastric lesions. Besides the pineal
      gland, melatonin is also generated in large amounts in the gastrointestinal tract
      and due to its antioxidant and anti-inflammatory properties; this indole might
      serve as local protective endogen preventing the development of acute gastric
      damage. The results of the present study indicate that stress-induced gastric
      lesions show circadian variations with an increase in the day time and a decline
      at night. These changes are inversely related to plasma melatonin levels.
      Following pinealectomy, stress-induced gastric mucosal lesions were more
      pronounced both during the day and at night, and were accompanied by markedly
      reduced plasma melatonin levels with a pronounced reduction in mucosal generation
      of prostaglandin E(2) (PGE(2)), GBF and increased free radical formation and by
      small rise in plasma melatonin during the dark phase. We conclude that stress
      induced gastric ulcerations exhibit a circadian variation with an increase in the
      day and attenuation at night and that these fluctuations of gastric stress
      ulcerogenesis occur also after pinealectomy, depending upon the interaction of
      COX-PG and free radicals, probably mediated by the changes in local gastric
      melatonin.

PMID- 18086150
TI  - Effects of drug hydrophobicity on liposomal stability.
AB  - A major obstacle in drug delivery is the inability to effectively deliver drugs
      to their intended biological target without deleterious side-effects. Delivery
      vehicles such as liposomes can minimize toxic side-effects by shielding the drug
      from reaction with unintended targets while in systemic circulation. Liposomes
      have the ability to accommodate both hydrophilic and hydrophobic drugs, either in
      the internal aqueous core or the lipid bilayer, respectively. In the present
      study, fluorescein and rhodamine have been used to model hydrophilic and
      hydrophobic drugs, respectively. We have compared the stabilities of liposomes
      encapsulating these fluorophores as a function of lipid content, time, and
      temperature. At 25 and 37 degrees C, liposomes containing distearoyl
      phosphatidylcholine as the major phospholipid component were found to be more
      stable over time than those containing dipalmitoyl phosphatidylcholine,
      regardless of the fluorophore encapsulated. Liposomes loaded with fluorescein
      were found to be more stable than those with rhodamine. Dipalmitoyl
      phosphatidylcholine liposomes that encapsulated rhodamine were the least stable.
      The results indicate that the physical properties of the drug cargo play a role
      in the stability, and hence drug delivery kinetics, of liposomal delivery
      systems, and desired drug release times can be achieved by adjusting/fine-tuning
      the lipid compositions.

PMID- 18086147
TI  - Melatonin maintains mitochondrial membrane potential and attenuates activation of
      initiator (casp-9) and effector caspases (casp-3/casp-7) and PARP in UVR-exposed
      HaCaT keratinocytes.
AB  - Melatonin is a recognized antioxidant with high potential as a protective agent
      in many conditions related to oxidative stress such as neurodegenerative
      diseases, ischemia/reperfusion syndromes, sepsis and aging. These processes may
      be favorably affected by melatonin through its radical scavenging properties
      and/or antiapoptotic activity. Also, there is increasing evidence that these
      effects of melatonin could be relevant in keratinocytes, the main cell population
      of the skin where it would contribute to protection against damage induced by
      ultraviolet radiation (UVR). We therefore investigated the kinetics of UVR
      induced apoptosis in cultured keratinocytes characterizing the morphological and
      mitochondrial changes, the caspases-dependent apoptotic pathways and involvement
      of poly(ADP-ribose) polymerase (PARP) activation as well as the protective
      effects of melatonin. When irradiated with UVB radiation (50 mJ/cm(2)), melatonin
      treated, cultured keratinocytes were more confluent, showed less cell blebbing,
      more uniform shape and less nuclear condensation as compared to irradiated,
      nonmelatonin-treated controls. Preincubation with melatonin also led to
      normalization of the decreased UVR-induced mitochondrial membrane potential.
      These melatonin effects were followed by suppression of the activation of
      mitochondrial pathway-related initiator caspase 9 (casp-9), but not of death
      receptor-dependent casp-8 between 24 and 48 hr after UVR exposure. Melatonin down
      regulated effector caspases (casp-3/casp-7) at 24-48 hr post-UV irradiation and
      reduced PARP activation at 24 hr. Thus, melatonin is particularly active in UV
      irradiated keratinocytes maintaining the mitochondrial membrane potential,
      inhibiting the consecutive activation of the intrinsic apoptotic pathway and
      reducing PARP activation. In conclusion, these data provide detailed evidence for
      specific antiapoptotic mechanisms of melatonin in UVR-induced damage of human
      keratinocytes.

PMID- 18086151
TI  - Synthesis, structural characterization and biological evaluation of novel
      [1,2,4]triazolo [1,5-b][1,2,4]benzothiadiazine-benzothiazole conjugates as
      potential anticancer agents.
AB  - Two series of 10-substituted 5,5-dioxo-5,10-dihydro[1,2,4]triazolo[1,5
      b][1,2,4]benzothiadiazine 2-methyl/ethyl sulfanyl benzothiazole derivatives (5a
      d) and 10-substituted 5,5-dioxo-5,10-dihydro[1,2,4]triazolo[1,5-b][1,2,4]
      benzothiadiazine 2-phenoxy benzothiazole derivatives (16a-c) were synthesized and
      their structures confirmed by NMR, MS, IR and X-ray crystallography. These
      compounds were evaluated for their cytotoxicity against 60 human tumour cell
      lines. One of the synthesized compounds (5b) exhibited significant inhibitory
      activity against most of the cell lines and has been further evaluated for the
      five-dose screening.

PMID- 18086148
TI  - Melatonin attenuates calpain upregulation, axonal damage and neuronal death in
      spinal cord injury in rats.
AB  - Multiple investigations in vivo have shown that melatonin (MEL) has a
      neuroprotective effect in the treatment of spinal cord injury (SCI). This study
      investigates the role of MEL as an intervening agent for ameliorating Ca(2+)
      mediated events, including activation of calpain, following its administration to
      rats sustaining experimental SCI. Calpain, a Ca(2+)-dependent neutral protease,
      is known to be involved in the pathogenesis of SCI. Rats were injured using a
      standard weight-drop method that induced a moderately severe injury (40 g.cm
      force) at T10. Sham controls received laminectomy only. Injured animals were
      given either 45 mg/kg MEL or vehicle at 15 min post-injury by intraperitoneal
      injection. At 48 hr post-injury, spinal cord (SC) samples were collected.
      Immunofluorescent labelings were used to identify calpain expression in specific
      cell types, such as neurons, glia, or macrophages. Combination of terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and
      double immunofluorescent labelings was used to identify apoptosis in specific
      cells in the SC. The effect of MEL on axonal damage was also investigated using
      antibody specific for dephosphorylated neurofilament protein (dNFP). Treatment of
      SCI animals with MEL attenuated calpain expression, inflammation, axonal damage
      (dNFP), and neuronal death, indicating that MEL provided neuroprotective effect
      in SCI. Further, expression and activity of calpain and caspse-3 were examined by
      Western blotting. The results indicated a significant decrease in expression and
      activity of calpain and caspse-3 in SCI animals after treatment with MEL. Taken
      together, this study strongly suggested that MEL could be an effective
      neuroprotective agent for treatment of SCI.

PMID- 18086152
TI  - Selective mapping of chemical space for Pseudomonas aeruginosa deacetylase LpxC
      inhibitory potential.
AB  - UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc deacetylase enzyme of Pseudomonas
      aeruginosa is an interesting target for development of anti-infective drugs
      against this gram-negative bacterium. Many segregated studies analyzing the P.
      aeruginosa UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc deacetylase and its inhibitors
      have been reported in the recent past. In the present study, an attempt has been
      made to integrate this knowledge for the development of an effective multilayer
      screening approach. Eventually, an extensive chemical space was screened to
      filter out three potential P. aeruginosa UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc
      deacetylase inhibitors.

PMID- 18086153
TI  - Novel PPAR-gamma agonists identified from a natural product library: a virtual
      screening, induced-fit docking and biological assay study.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays an essential
      role in lipid and glucose homeostasis. It is recognized as the receptor of the
      thiazolidinediones-a synthetic class of anti-diabetic drugs-and is the target of
      many drug discovery efforts because of its role in disease states, such as type
      II diabetes mellitus. In this study, structure-based virtual screening of the
      PPAR-gamma ligand binding domain against a natural product library has revealed
      29 potential agonists. In vitro testing of this list identified six flavonoids to
      have stimulated PPAR-gamma transcriptional activity in a transcriptional factor
      assay. Of these, flavonoid-psi-baptigenin-was classed as the most potent PPAR
      gamma agonist, possessing low micromolar affinity (EC(50) = 2.9 microM). Further
      in vitro testing using quantitative RT-PCR and immunoblotting experiments
      demonstrated that psi-baptigenin activated PPAR-gamma mRNA (4.1 +/- 0.2-fold) and
      protein levels (2.9 +/- 0.4-fold) in THP-1 macrophages. Moreover, psi
      baptigenin's-induced PPAR-gamma enhancement was abolished in the presence of a
      selective PPAR-gamma antagonist, GW9662. Induced-fit docking investigations
      provide a detailed understanding on the ligands' mechanism of action, suggesting
      five of the active flavonoids induce significant conformational change in the
      receptor upon binding. Overall, these results offer insight into various
      naturally derived flavonoids as leads/templates for development of novel PPAR
      gamma ligands.

PMID- 18086154
TI  - The effect of trilostane treatment on circulating thyroid hormone concentrations
      in dogs with pituitary-dependent hyperadrenocorticism.
AB  - OBJECTIVE: To assess thyroid hormone levels in hyperadrenocorticoid dogs before
      and after therapy with trilostane, a reversible inhibitor of steroidogenesis.
      METHODS: Serum total thyroxine, free thyroxine and endogenous canine thyroid
      stimulating hormone concentrations were measured in 20 dogs with spontaneously
      occurring hyperadrenocorticism before and six months after successful treatment
      with trilostane. RESULTS: Fourteen dogs demonstrated an increase in thyroxine
      following trilostane treatment; however, this was not significant (P=0.108).
      Fourteen dogs demonstrated an increase in canine thyroid-stimulating hormone
      concentrations with trilostane therapy (P=0.006). Of the 14 dogs that
      demonstrated an increase in thyroxine concentrations following therapy, 10 also
      showed an increase in canine thyroid-stimulating hormone concentrations. Before
      treatment, free thyroxine values were within, above and below the reference range
      in 10, six and two dogs, respectively. Sixteen of 18 dogs had free thyroxine
      values within the reference range after treatment, with 11 dogs showing a
      decrease in free thyroxine levels following therapy (P=0.029). CLINICAL
      SIGNIFICANCE: While treatment with trilostane did not induce a significant change
      of thyroxine concentrations, there was a significant increase in canine thyroid
      stimulating hormone concentrations following treatment, a finding that supports
      thyroid-stimulating hormone suppression as one of the factors that contributes to
      the effects of glucocorticoids on the hypothalamic-pituitary-thyroid axis. The
      significant elevation in free thyroxine values following treatment with
      trilostane was unexpected and did not support the findings of previous studies in
      this area.

PMID- 18086155
TI  - Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a coati.
AB  - The aim of this report was to present a case of epitheliotropic cutaneous
      lymphoma (mycosis fungoides) in a coati. The animal was presented for evaluation
      of a non-pruritic nodule. Although the diagnosis of cutaneous histiocytoma was
      made histologically, plaques and erosions appeared in new areas of the skin along
      with rapid deterioration of body condition that led to euthanasia in less than
      one month following initial presentation. Epitheliotropic cutaneous lymphoma was
      confirmed with plaque biopsies. Cross-reactivity of a polyclonal antihuman CD3
      antibody to coati T lymphocytes was also observed. Apart from skin lesions, only
      pleuritis was post-mortem diagnosed most likely because of immunosuppression
      secondarily to malignant neoplasia.

PMID- 18086156
TI  - Subcutaneous abscess caused by Clostridium perfringens and osteomyelitis in a
      dog.
AB  - A case of a subcutaneous abscess caused by Clostridium perfringens infection in a
      five-month-old dog is reported in this study. Clinical examination, radiological
      findings and cytological analysis of abscess fluid were consistent with
      Clostridium induced disease. Treatment including drainage of the abscess and
      antibiotic therapy led to rapid clinical improvement. However, despite aggressive
      medical therapy and proper wound care, the deep soft tissue infection led to
      osteomyelitis with premature closure of the growth plates of the tibia and
      secondary bone shortening. Prolonged treatment with metronidazole and amoxicillin
      clavulanic acid resulted in an excellent outcome with normal weight bearing.

PMID- 18086157
TI  - Comparison of the prevalence of enteric viruses in healthy dogs and those with
      acute haemorrhagic diarrhoea by electron microscopy.
AB  - OBJECTIVES: To evaluate prevalence of enteric viruses in healthy dogs and to
      compare it with prevalences in dogs with acute haemorrhagic diarrhoea. METHODS:
      Faecal samples were collected from 200 healthy dogs and examined by electron
      microscopy for presence of viral particles. Data were compared with viral
      prevalences that had been determined retrospectively by electron microscopy for
      936 dogs with acute haemorrhagic diarrhoea. RESULTS: There were significantly
      more negative faecal samples among the healthy dogs (82.0 per cent) compared with
      55.8 per cent in dogs with acute haemorrhagic diarrhoea (P<0.001). With a
      prevalence of 17.5 per cent, significantly more healthy dogs were shedding
      coronavirus compared with 11.6 per cent in dogs with acute haemorrhagic diarrhoea
      (P=0.034). Parvovirus was only detected in one healthy dog (0.5 per cent), thus
      with a prevalence that was significantly lower than 16.0 per cent detected in the
      dogs with acute haemorrhagic diarrhoea (P<0.001). Paramyxovirus was not found in
      any of the healthy dogs but was found in 9.3 per cent of dogs with acute
      haemorrhagic diarrhoea (P<0.001). CLINICAL SIGNIFICANCE: Results suggest that
      shedding of parvovirus and paramyxovirus is strongly associated with acute
      haemorrhagic diarrhoea. However, coronavirus seems to be even more prevalent
      among healthy dogs, raising the need for further studies to investigate the
      strain-associated pathogenicity of this virus.

PMID- 18086158
TI  - Complications following tarsal arthrodesis using bone plate fixation in dogs.
AB  - OBJECTIVES: To report the complications encountered following tarsal arthrodesis
      surgery with bone plate fixation and describe the previously unreported
      complication of plantar necrosis. METHODS: Medical records of 40 dogs that had
      been treated by tarsal arthrodesis with bone plate fixation were reviewed to
      determine the major and minor complications and the associated risk factors.
      RESULTS: The major complication rate was 32.5 per cent and the minor complication
      rate was 42.5 per cent. Pantarsal arthrodeses had a higher major complication
      rate than partial tarsal arthrodeses. Plantar necrosis was the most common major
      complication and occurred in 15 per cent of cases. Plantar necrosis occurred more
      frequently when a bone plate was applied to the medial aspect of the hock, and
      only occurred in cases where tarsometatarsal joint arthrodesis was performed.
      CLINICAL SIGNIFICANCE: Plantar necrosis is a catastrophic complication that may
      be associated with injury to the dorsal pedal artery or perforating metatarsal
      artery. Application of a bone plate to the medial aspect of the hock should be
      performed with care during tarsal arthrodesis, particularly where the
      tarsometatarsal joint is debrided of cartilage. Strict attention to surgical
      technique and proper postoperative coaptation is critical to reduce the potential
      for complications with tarsal arthrodesis.

PMID- 18086159
TI  - Giving patients with erectile dysfunction the opportunity to try all three
      available phosphodiesterase type 5 inhibitors contributes to better long-term
      treatment compliance.
AB  - INTRODUCTION: There are three phosphodiesterase type 5 (PDE5) inhibitors
      marketed, sildenafil, Vardenafil, and tadalafil for oral treatment of erectile
      dysfunction (ED). Although the treatment is simple and mostly effective, around
      50% has ceased to use the medication within 2 years. One recently described way
      to improve the compliance is to let the patient try all the three PDE5 inhibitors
      and to prescribe the drug(s) he and his partner desires. AIM: To study long-term
      compliance among patients who were treated according to this "three-drug regime."
      MAIN OUTCOME MEASURES: Compliance and reasons for discontinuation after >2 years.
      METHODS: The men who, during 2003, were enrolled in a treatment regime, where
      they had the opportunity to test all the three drugs and to chose the one(s) they
      preferred, were interviewed in 2006 by telephone concerning their ongoing ED
      treatment and the reason for discontinuation. RESULTS: Of the 138 men, mean age
      60 years (36-79 years), who had been enrolled and successfully treated with the
      three-drug regime, 127 (92%) could be reached. The mean follow-up time was 27
      months (23-34 months). Of the 127 men, as many as 109 (86%) were still using PDE5
      inhibitors. A few (8%) used more than two tablets per week. The majority (44%)
      used one to two tablets per week or one to two per month (43%), the others (5%)
      less often. The causes for discontinuation were varying. The most common reason
      (N = 7) was return of a satisfactory non-assisted erection. Seventy-five percent
      of the men used only one drug; the others switched between a short- and long
      acting drug depending on the situation. It was not uncommon (25%) that the
      preference had changed during the 3 years of PDE5 inhibitor use. CONCLUSION: To
      let patients with ED test the three available PDE5 inhibitors results in an
      unusually high compliance even under an extended period of time (>2 years).

PMID- 18086160
TI  - Baseline prevalence of erectile dysfunction in a prostate cancer screening
      population.
AB  - INTRODUCTION: Erectile dysfunction (ED) is common in older men and can be
      worsened by prostate cancer (PCa) treatment. True ED rates before PCa treatment
      are mandatory, in order to assess the rate of ED attributable to PCa treatment.
      Data derived from population-based studies or from patients surveyed after PCa
      diagnosis, as well as just prior to treatment may not represent a valid
      benchmark, as health profiles of the general population might be different to
      those undergoing PCa screening or as anxiety may worsen existent ED. AIM: To
      circumvent these limitations, we assessed the baseline rate of ED in PCa
      diagnosis-free men participating in a PCa awareness event. METHODS: ED was
      classified according to the International Index of Erectile Function (IIEF) score
      as absent (IIEF: 25-30), mild (22-24), mild to moderate (17-21), moderate (11
      16), or severe (</=10). Analyses were adjusted according to age and socioeconomic
      status. MAIN OUTCOME MEASURES: Of 1,273 asymptomatic men who participated in the
      event, 1,134 (89.1%) completed the IIEF score. RESULTS: Mean age was 57.6 years
      (range 40-89 years). Of all participating men, 50.0% (N = 566) were potent, 8.8%
      (N = 100) reported mild, 10.4% (N = 118) mild to moderate, 9.4% (N = 107)
      moderate, and 21.4% (N = 243) severe ED. Men with ED were significantly older (P
      < 0.001), had no stable partner (P < 0.001), lower education (P < 0.001), and
      lower annual income (P < 0.001) than men without ED. CONCLUSIONS: One in two men
      who participated in this PCa awareness event is affected by ED, independent of
      PCa diagnosis or treatment. Such high prevalence of baseline ED in a PCa
      screening cohort suggests that in patients treated for PCa, ED may represent a
      common disorder already present prior to treatment. Moreover, socioeconomic
      variables were seen to have an important influence on erectile function in this
      patient cohort.

PMID- 18086161
TI  - The female sexual response cycle: do Malaysian women conform to the circular
      model?
AB  - INTRODUCTION: The concept of a sexual response cycle (SRC) for women has gained
      interest lately with the reintroduction of terms with new definitions and a new
      model for the sexual response, especially the Basson's circular model. AIM: To
      determine the correlations among the SRC's phases (i.e., sexual desire, sexual
      arousal, orgasm, sexual satisfaction, and sexual pain) in Malaysian women, in
      order to validate the circular model of women's SRC. METHODS: Principal component
      analysis (PCA), a factor analysis technique with varimax rotation method, was
      used to explore the correlation structure of items in female respondents who
      scored on the Malay version of Female Sexual Function Index (FSFI). The number of
      factors or components to obtain was decided using Kaiser's criteria. MAIN OUTCOME
      MEASURE: To measure the correlation between female SRC's domain. RESULTS: A total
      of 230 married women aged 18-70 years old participated in this study. Factor
      loadings using PCA with varimax rotation divided the sexual domains into three
      components based on Kaiser's criteria with eigenvalues of 6.11, 5.59, and 3.50,
      respectively. Sexual desire, sexual arousal, and lubrication were highly
      correlated, and therefore, they fall in one component, reflecting one construct,
      whereas orgasm and sexual satisfaction fall in another component. The third
      component was formed by the pain items. CONCLUSION: The strong correlation
      between sexual desire/arousal/lubrication means that they were the same and may
      support the contemporary theory of circular model of SRC in women.

PMID- 18086162
TI  - An evidence-based perspective to commonly performed erectile dysfunction
      investigations.
AB  - INTRODUCTION: Currently there is no universally accepted gold standard diagnostic
      test to differentiate psychogenic from physical erectile dysfunction (ED).
      Instead, sexual health specialists rely on a detailed history, a focused physical
      examination, and specialized diagnostic tests, to decide if the etiology of the
      ED is mainly psychogenic or organically caused. Aim. In this review we point out
      the status of evidence-based principles in the area of diagnosis in Sexual
      Medicine. METHODS: We review the concepts of evidence-based medicine (EBM) in the
      area of medical diagnostic tests. We highlight four of the well-known diagnostic
      tests (penile duplex, pharmacoarteriography,
      pharmacocavernosometry/cavernosography [PHCAS/PHCAG], and nocturnal penile
      tumescence [NPT monitoring]) for ED evaluation within an evidence-based
      perspective. MAIN OUTCOME MEASURES: Assessment of diagnostic tests for ED using
      principles of EBM. RESULTS: Several good diagnostic tests are useful in the
      evaluation of men with ED. However, modern evidence-based concepts-mainly the
      likelihood ratio-have not yet been applied to these tests to obtain their maximum
      clinical benefits. CONCLUSIONS: While penile duplex/color Doppler has good
      evidence of supporting its use in the diagnosis of arteriogenic ED, data
      supporting its diagnosis of a physical disorder associated with cavernous venous
      occlusion dysfunction are lacking. PHCAS/PHCAG's main drawback is an unknown
      positive predictive value and a possibility of frequent false-positive results.
      NPT has many advantages when differentiating psychogenic from organic ED,
      however, several questions related to its physiological mechanisms do exist.
      Ghanem H, and Shamloul R. An evidence-based perspective to commonly performed
      erectile dysfunction investigations.

PMID- 18086164
TI  - Psychosexual characteristics of vestibulodynia couples: partner solicitousness
      and hostility are associated with pain.
AB  - INTRODUCTION: Provoked vestibulodynia is a prevalent yet misunderstood women's
      sexual health issue. In particular, data concerning relationship characteristics
      and psychosexual functioning of partners of these women are scarce. Moreover, no
      research to date has examined the role of the partner in vestibulodynia. AIMS:
      This study aimed to characterize and compare the psychosexual profiles of women
      with vestibulodynia and their partners, in addition to exploring whether partner
      related variables correlated with women's pain and associated psychosexual
      functioning. METHODS: Forty-three couples in which the woman suffered from
      vestibulodynia completed self-report questionnaires focusing on their sexual
      functioning, dyadic adjustment, and psychological adjustment. Women were
      diagnosed using the cotton-swab test during a standardized gynecological
      examination. They also took part in a structured interview during which they were
      asked about their pain during intercourse and frequency of intercourse. They also
      completed a questionnaire about their perceptions of their partners' responses to
      the pain. MAIN OUTCOME MEASURES: Dependent measures for both members of the
      couple included the Sexual History Form, the Locke-Wallace Marital Adjustment
      Scale and the Brief Symptom Inventory. Women completed a horizontal analog scale
      assessing the intensity of their pain during intercourse and reported their
      frequency of intercourse per month. RESULTS: Findings show that women with
      vestibulodynia and their partners did not differ from population norms with
      regard to global sexual functioning, dyadic adjustment and psychological
      adjustment. However, mean frequency of intercourse was lower than the standard
      for this age group. Also, women had significantly poorer sexual functioning than
      men. In addition, a regression analysis revealed that partner solicitousness and
      hostility were significantly associated with higher levels of pain during
      intercourse. CONCLUSIONS: Results suggest that although the psychosexual and
      relationship characteristics of partners of women with vestibulodynia are within
      norms, their responses may play a role in the experience of pain.

PMID- 18086163
TI  - Snoring as a risk factor for sexual dysfunction in community men.
AB  - INTRODUCTION: Severe obstructive sleep apnea has been associated with sexual
      dysfunction; however, it is unclear whether milder forms of sleep disturbances
      might also be associated with sexual problems. AIM: To evaluate the association
      between snoring and five measures of sexual dysfunction in a population-based
      sample of men. METHODS: A stratified random sample of men residing in Olmsted
      County, Minnesota completed a questionnaire containing questions from the Brief
      Male Sexual Function Inventory (BMSFI) and a sleep questionnaire. MAIN OUTCOME
      MEASURES: Levels of sexual drive (libido), erectile function, ejaculatory
      function, sexual problem assessment, and sexual satisfaction as assessed by the
      BMSFI. RESULTS: Of 827 men with a regular sexual partner, subjects were divided
      into categories of heavy (N = 95), moderate (N = 573), and none/mild (N = 159)
      snoring. Their median age was 64 years (range 51-90). The sexual satisfaction
      domain score was significantly lower in the heavy snoring group (P value = 0.01).
      The odds of low sexual satisfaction was 2.3 (95% CI 1.2, 4.1) among the heavy
      snorers compared with the none/mild snoring group. This association remained
      statistically significant after adjustment for smoking, medical comorbidities,
      and mental health status. However, there was no significant difference in
      ejaculatory function, erectile function, sexual drive, and sexual problem
      assessment across snoring categories. CONCLUSIONS: These data provide evidence of
      an association between snoring severity and reduced sexual satisfaction in a
      population of elderly community males. Snoring was not associated with biologic
      measures of sexual dysfunction.

PMID- 18086165
TI  - Quality of erections in men treated with flexible-dose sildenafil for erectile
      dysfunction: multicenter trial with a double-blind, randomized, placebo
      controlled phase and an open-label phase.
AB  - INTRODUCTION: Erectile dysfunction (ED) impacts erection hardness and compromises
      quality of life. AIM: Assess erection hardness and its correlation with sexual
      function, emotional well-being, and satisfaction (erection quality, intercourse,
      sex life, sexual relationship, and treatment). METHODS: Men with ED were
      randomized to double-blind, flexible-dose sildenafil (25, 50, or 100 mg) or
      placebo (6 weeks) with open-label extension (6 weeks). MAIN OUTCOME MEASURES:
      Erection Hardness Score (EHS), Quality of Erection Questionnaire (QEQ),
      International Index of Erectile Function (IIEF), Self-Esteem And Relationship
      (SEAR) questionnaire, and Erectile Dysfunction Inventory of Treatment
      Satisfaction (EDITS). RESULTS: A total of 307 men (mean [range] age, 45 [18-55]
      years) were randomized to sildenafil (N = 154) or placebo (N = 153). At the end
      of double-blind treatment, occasions with EHS 3 (hard enough for penetration but
      not completely hard) or 4 (completely hard) had increased by 40% +/- 3% for
      sildenafil vs. 11% +/- 3% for placebo (least squares mean +/- standard error; P <
      0.0001); the estimated percentage of occasions with EHS 4 was 58% (95% CI, 52
      65%) vs. 14% (95% CI, 10-19%) (odds ratio, 8.5; P < 0.0001). There was greater
      improvement in mean QEQ, IIEF, and SEAR scores (P < 0.0001), and more men were
      satisfied with sildenafil treatment (EDITS Index score >50: 90% vs. 49%). QEQ,
      IIEF, SEAR, and EDITS outcomes correlated positively with EHS 3 or 4, and with
      EHS 4 alone and were highest (no overlap of 95% CI vs. other EHS subgroups) in
      the subgroup with most frequent EHS of 4. CONCLUSIONS: In the group of men with
      ED treated with sildenafil, it was estimated that completely hard erections were
      achieved on 58% (95% CI, 52-65%) of occasions. Improvement in function, emotional
      well-being, and satisfaction was greatest in men with completely hard erections
      and correlated positively with other measures of hardness.

PMID- 18086166
TI  - Hydrogen sulfide inhibits cell proliferation and induces cell cycle arrest via an
      elevated p21 Cip1 level in Ca9-22 cells.
AB  - BACKGROUND AND OBJECTIVE: Volatile sulfur compounds such as hydrogen sulfide
      (H(2)S) and methyl mercaptan (CH(3)SH) are the main causes of oral mal odor.
      However, the physiological functions of H(2)S have not been investigated in oral
      tissues. The aim of this study was to evaluate the effect of H(2)S on cell
      proliferation and the cell cycle in oral epithelial-like cells. MATERIAL AND
      METHODS: Ca9-22 cells were used in this study. Cells were cultured in 5%
      CO(2)/95% air with (5 or 10 ng/mL) or without H(2)S. DNA synthesis was measured
      using a 5-bromo-2-deoxyuridine enzyme-linked immunosorbent assay. The cell cycle
      was analyzed using a flow cytometer. The expressions of phosphorylated
      retinoblastoma protein (Rb), p21(Cip1) and p27(Kip1) were evaluated by western
      blotting. RESULTS: Exposure to 5 and 10 ng/mL of H(2)S significantly decreased
      DNA synthesis (p < 0.05). Cell cycle analysis also showed that exposure to both
      concentrations of H(2)S significantly increased the proportion of cells in G(1)
      phase (p < 0.001) and significantly decreased the proportion of cells in S phase
      (p < 0.01). Western blotting showed that Rb phosphorylation was reduced and
      p21(Cip1) was enhanced by exposure to H(2)S. CONCLUSION: The results indicated
      that H(2)S inhibits cell proliferation and induces cell cycle arrest via the
      expression of p21(Cip1) in Ca9-22 cells.

PMID- 18086167
TI  - Cellular responses of rat periodontal ligament cells under hypoxia and re
      oxygenation conditions in vitro.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the responses
      of periodontal ligament cells under hypoxia and re-oxygenation conditions in
      vitro. MATERIAL AND METHODS: Periodontal ligament fibroblasts were isolated from
      rat incisors. In the hypoxia group, cells were incubated in 2% O(2) for 1-3 d. In
      the re-oxygenation group, cells were first incubated under the same conditions as
      the hypoxia group for 24 h and then were returned to normoxic conditions and
      cultured for 1-2 additional days. RESULTS: Proliferation ratios increased in all
      groups in a time-dependent manner. Proliferation ratios in both the hypoxia and
      re-oxygenation groups were significantly higher than in the control group on days
      2 and 3. Alkaline phosphatase activity was significantly higher in the hypoxia
      group than in the control and the re-oxygenation groups. The expression of bone
      sialoprotein mRNA was significantly higher in the hypoxia group than in the
      control group on days 1 and 2. The expression of vascular endothelial growth
      factor mRNA was significantly higher in the hypoxia group than in the control
      group on days 1 and 2. In the re-oxygenation group, the level of expression of
      bone sialoprotein mRNA and vascular endothelial growth factor mRNA were similar
      to those of the control group. The expression of heat shock protein 70 mRNA in
      the hypoxia group was similar to that in the control group, whereas in the re
      oxygenation group it was statistically higher than in the other groups.
      CONCLUSION: These results suggest that periodontal ligament cells maintain their
      osteogenic ability in hypoxia and re-oxygenation conditions in vitro.

PMID- 18086168
TI  - Quantitative analysis of association between herpesviruses and bacterial
      pathogens in periodontitis.
AB  - BACKGROUND AND OBJECTIVE: The development of human periodontitis may depend upon
      cooperative interactions among herpesviruses, specific pathogenic bacteria and
      tissue-destructive inflammatory mediators. This study sought to identify
      associations among human cytomegalovirus, Epstein-Barr virus and six putative
      periodontopathic bacteria in periodontitis lesions. MATERIAL AND METHODS: Fifteen
      periodontitis patients (nine with aggressive periodontitis and six with chronic
      periodontitis) and 15 periodontally normal subjects were included in the study.
      In each study subject, a microbiological sample was collected, using a curette,
      from the deepest periodontal probing depth of the dentition. A real-time TaqMan
      polymerase chain reaction assay was employed to determine the subgingival counts
      of human cytomegalovirus, Epstein-Barr virus, Porphyromonas gingivalis,
      Tannerella forsythia, Prevotella intermedia, Aggregatibacter
      actinomycetemcomitans, Fusobacterium nucleatum and Campylobacter rectus.
      Statistical analysis was performed using the Student's t-test, the Pearson
      correlation coefficient test and the single variable logistic regression test for
      odds ratio-based risk calculation. RESULTS: Human cytomegalovirus was detected in
      eight periodontitis lesions and in one normal periodontal site, Epstein-Barr
      virus was detected in nine periodontitis lesions and in two normal periodontal
      sites, and the study bacteria were detected in 6-15 periodontitis lesions and in
      1-11 normal periodontal sites. Correlations were found between counts of human
      cytomegalovirus and Epstein-Barr virus, between counts of human cytomegalovirus
      and P. gingivalis, T. forsythia and C. rectus, and between counts of Epstein-Barr
      virus and P. gingivalis and T. forsythia. Human cytomegalovirus and Epstein-Barr
      virus counts were also positively associated with the level of periodontal
      attachment loss, probing pocket depth and gingival bleeding on probing.
      CONCLUSION: This study confirmed that periodontal human cytomegalovirus and
      Epstein-Barr virus are associated with major periodontopathic bacteria and with
      the severity of periodontal disease. The finding of abundant herpesviruses in
      periodontitis lesions redefines the pathogenic paradigm of the disease.
      Understanding the interplay between herpesviruses and specific bacterial species
      in the pathogenesis of periodontitis may form the basis for new approaches to
      preventing, reducing or delaying tissue breakdown from periodontal infections.

PMID- 18086169
TI  - Cultured human periodontal ligament cells constitutively express multiple
      osteotropic cytokines and growth factors, several of which are responsive to
      mechanical deformation.
AB  - BACKGROUND AND OBJECTIVE: A role for cytokines and growth factors in mediating
      the cellular and molecular events involved in orthodontic tooth movement is well
      established. The focus to date, however, has been largely on individual
      mediators, rather than to study cytokines in terms of complex interacting
      networks. Our objective was to expand our knowledge of the cytokines and growth
      factors expressed by human periodontal ligament (PDL) cells and to identify new
      genes that are responsive to mechanical deformation. MATERIAL AND METHODS: Human
      PDL cells were strained with a cyclic deformation of 12% for 6-24 h, and the
      differential expression of 79 cytokine and growth factor genes was quantified
      using real-time RT-PCR arrays. For statistical comparison, t-tests were used with
      mean critical threshold (CT) values derived from triplicate samples. RESULTS:
      Forty-one genes were detected at CT values < 35 and, of these, 15 showed a
      significant change in relative expression. These included seven interleukins
      (IL): IL1A, IL1F7, IL6 and IL7 (down), IL8, IL11 and IL12A (up). Eight genes
      representing other cytokine and growth factor families showed comparable
      mechanical sensitivity, including VEGFD and OPG (down) and PDGFA, INHBA, GDF8 and
      two transforming growth factor beta genes, TGFB1 and TGFB3 (up). The genes
      CSF2/GMCSF and IL11 were found to be consistently stimulated across all three
      time points. Genes that were not expressed included: (1) the immunoregulatory
      lymphokines (IL2-IL5), IL17 and IL17B; (2) IL10 and other members of the IL-10
      family of anti-inflammatory cytokines (IL19, IL20, IL22 and IL24); and (3) TNF
      and RANKL. CONCLUSION: Human PDL cells constitutively express numerous
      osteotropic cytokines and growth factors, many of which are mechanoresponsive.

PMID- 18086170
TI  - Return of nocturnal erections and erectile function after bilateral nerve-sparing
      radical prostatectomy in men treated nightly with sildenafil citrate: subanalysis
      of a longitudinal randomized double-blind placebo-controlled trial.
AB  - INTRODUCTION: After bilateral nerve-sparing radical retropubic prostatectomy
      (BNSRRP), nocturnal and sexually mediated erections may help to preserve normal
      erectile function (EF). AIM: To investigate nocturnal penile tumescence and
      rigidity (NPTR) in a subset (N = 54 men) from a randomized, double-blind trial (N
      = 76) of nightly sildenafil after BNSRRP. METHODS: Inclusion required
      preoperative "normal" EF (defined as a combined score of >/=8 for International
      Index of Erectile Function questions 3 (penetration) and 4 (maintained erection
      after penetration) and NPTR testing (>/=10 continuous minutes of >/=55% rigidity
      [R >/= 55%] at the base). Postoperative assessments were at weeks 4
      (pretreatment), 16, 28, 40 (during 36 weeks of nightly prophylaxis: sildenafil 50
      mg [N = 17], 100 mg [N = 18] or placebo [N = 19]), and 48 (after 8 weeks of no
      erectile dysfunction therapy, when "responders" were delineated by the defined
      normal EF and a "yes" response to "Over the past 4 weeks, have your erections
      been good enough for satisfactory sexual activity?"). Base and tip rigidity and
      tumescence were measured using penile plethysmography. MAIN OUTCOME MEASURES:
      Duration of R >/= 55% and area under the curves for rigidity and tumescence.
      RESULTS: Postoperatively, rapid profound reduction in nocturnal EF was noted in
      all groups. There was a gradual dose-dependent improvement in base and tip
      rigidity in the sildenafil groups but little improvement in the placebo group.
      Eight weeks after treatment termination (48 weeks postoperatively), 24% (4/17) of
      50-mg sildenafil recipients, 33% (6/18) of 100-mg sildenafil recipients, and 5%
      (1/19) of placebo recipients were responders. Tip R >/= 55% was the most
      discriminating NPTR measure between nonresponders and responders to sildenafil,
      in whom it regained baseline (preoperative) levels (whereas base R >/= 55% did
      not). It was most prolonged in responders to sildenafil 100 mg. CONCLUSIONS: In
      our subset analysis, nightly sildenafil for 9 months post-BNSRRP objectively
      improved nocturnal erections and pharmaceutically unassisted EF.

PMID- 18086171
TI  - Male anorgasmia treated with oxytocin.
AB  - Introduction. This is a case report on male anorgasmia that was successfully
      treated with oxytocin. Oxytocin is increased during arousal and peaks during
      orgasm. More recently, a study on humans published in Nature has shown its value
      in social bonding, increasing trust, and enhancing the sense of well-being. Aim.
      To test the effectiveness of administering oxytocin in a case of treatment
      resistant anorgasmia. Methods. The patient underwent a biopsychosocial evaluation
      by a psychiatrist trained in sexual medicine and sex therapy for male orgasmic
      disorder, acquired type. Medical conditions, effect of substances, and
      psychological issues were ruled out. The patient was properly consented to using
      oxytocin as an off-label trial. Oxytocin was administered using a nasal spray
      intracoitally because of its ultra-short half-life. Results. Oxytocin was
      effective in restoring ejaculation. Conclusions. A case of treatment-resistant
      male anorgasmia was successfully treated with intracoital administration of
      intranasal oxytocin.

PMID- 18086172
TI  - Premature ejaculation in infertile couples: prevalence and correlates.
AB  - INTRODUCTION: The incidence of premature ejaculation (PE) and other sexual
      problems in infertile couples is unknown. AIMS: We attempted to determine the
      prevalence of PE in infertile couples. METHODS: Infertile couples presenting for
      evaluation at our institutions were invited to participate in our study. Multiple
      regression analysis was conducted to assess for associations between partner
      responses. MAIN OUTCOME MEASURE: Respondents completed a demographic survey, the
      Short Form-36 (SF-36), and the Center for Epidemiological Studies Depression (CES
      D) scale. Both partners also completed a gender-specific survey instrument to
      detect PE and distress related to the condition. Male partners completed the
      International Index of Erectile Function (IIEF) and the Self-Esteem and
      Relationship Quality (SEAR) scale. Female partners completed the Female Sexual
      Function Index (FSFI) and a modified version of the SEAR. RESULTS: Fifty percent
      of men reported that they ejaculated more rapidly than they wished. When men
      reported PE, their partners agreed with the diagnosis in 47% of cases. Female
      partners of men who did not report PE reported PE in 11% of cases. Partner
      frustration related to PE was reported by 30% of men. Partners agreed that they
      were frustrated in 43% of these cases. Among the 70% of men who did not report
      partner frustration from PE, 93% of the partners agreed that they were not
      frustrated. There was a statistically significant negative association between
      male and female report of PE and SEAR scores. There were no other statistically
      significant associations between PE responses and demographic variables, IIEF,
      FSFI, CES-D, and SF-36 scores. CONCLUSIONS: PE is prevalent among infertile
      couples although the perceived incidence of the condition among men is higher
      than partner perceived incidence. Additionally, many men may overestimate the
      level of partner frustration related to PE. PE is associated with lower
      relationship satisfaction in both men and women. Further research is required.

PMID- 18086173
TI  - Evaluation of sexual dysfunction prevalence in infertile couples.
AB  - INTRODUCTION: The physical health and emotional well-being of many individuals
      and couples of reproductive age are significantly affected by infertility. Sexual
      function is one of the important components of health and overall quality of
      life. AIMS: To determine the prevalence of sexual dysfunction in infertile
      couples. METHODS: In a cross-sectional study, in a tertiary university hospital,
      sexual dysfunction was assessed in 100 infertile couples. Sexual Function
      Questionnaire (SFQ) and International Index of Erectile Function (IIEF)
      questionnaire were administered. MAIN OUTCOME MEASURES: Prevalence of sexual
      dysfunction in infertile couples based on the score of the domains of SFQ and
      IIEF. RESULT(S): The SFQ score was within the normal range in all five domains in
      only 7% of women. The prevalence of female sexual dysfunction was highest and
      lowest in arousal-sensation (80.2%) and orgasm (22.8%) domains, respectively.
      Only 2% of male participants have had severe erectile dysfunction (ED).
      CONCLUSIONS: The prevalence of dysfunction in arousal-sensation and arousal
      lubrication in our study was found to be higher than the results reported from
      Iranian normal population. The prevalence of any degree of ED in our study was
      higher than the prevalence reported for normal population and infertile men. The
      role of demographic factors, relationship parameters, and infertility per se in
      the prevalence of sexual dysfunction in infertile couples remains to be
      determined.

PMID- 18086174
TI  - Improvement in sexual functioning in patients with interstitial cystitis/painful
      bladder syndrome.
AB  - INTRODUCTION: Sexual functioning is one of the strongest predictors of poorer
      quality of life (QOL) in patients diagnosed with interstitial cystitis/painful
      bladder syndrome (IC/PBS). AIMS: To examine the relationship between symptom
      reduction and sexual functioning in patients with IC/PBS. METHODS: Patients with
      IC/PBS were treated with 300 mg/day pentosan polysulfate sodium for 32 weeks.
      MAIN OUTCOME MEASURES: Patients completed the O'Leary-Sant Interstitial Cystitis
      Symptom Index, Short Form-12 QOL, and Medical Outcomes Study Sexual Functioning
      Scale at baseline, and at 8, 16, 24, and 32 weeks. Treatment responders were
      defined as those achieving a >/=30% reduction in symptom index from baseline.
      RESULTS: A total of 128 patients were included in the analyses. At baseline, mean
      symptom index, QOL (physical and mental), and sexual functioning scores were
      12.3, 41.7, 45.9, and 56.1, respectively. Patients showed statistically
      significant improvement in symptom and sexual functioning scores at weeks 8, 16,
      24, and 32. At week 32, the mean change in symptom index score from baseline was 
      2.97 (standard deviation [SD] = 4.66, P < 0.0001), and the mean change in sexual
      functioning score from baseline was 8.9 (SD = 32.9, P = 0.0054). Reduction in
      symptom index score was moderately correlated with improvement in sexual
      functioning score at the end of study (r = -35, P = 0.0002). Positive correlation
      was observed at the end of the study between the mean change scores of sexual
      functioning score and physical and mental QOL components (r = 0.46, P < 0.0001
      and r = 0.29, P = 0.0023, respectively). Patients achieving a >/=30% reduction in
      symptom index (responder, N = 47; 44%) had an adjusted mean change in sexual
      functioning score of 19.8 (standard error [SE] = 4.69), while nonresponders (N =
      59, 56%) had an adjusted mean change -0.49 (SE = 4.17) (between groups, P =
      0.0020). CONCLUSIONS: Sexual dysfunction is moderate to severe in patients with
      IC/PBS and impacts significantly on QOL. Reduction in symptoms was associated
      with improvement in the patient-reported outcomes of sexual function.

PMID- 18086175
TI  - The frequency of sexual intercourse reported by women: a review of community
      based studies and factors limiting their conclusions.
AB  - INTRODUCTION: A range of methodological inconsistencies has the potential to
      affect reported prevalence rates of sexual intercourse. AIMS: We reviewed
      published studies of sexual intercourse frequency reported by women and
      associated factors. METHODS: Literature search of electronic databases. Inclusion
      criteria for selected cross-sectional studies were population and community-based
      studies of frequency of intercourse in women published in English or German
      languages with sample size greater than 300. Longitudinal studies were selected
      if duration was at least 1 year and samples were not clinically based. MAIN
      OUTCOME MEASURES: Frequency of sexual intercourse/activities and any associated
      factors. RESULTS: There was a great deal of variation in the mean frequency of
      intercourse across all age groups with higher rates reported by European and
      American women. There was a reduction in frequency of sexual intercourse from age
      50 among women from Europe and the United States. Asian women reported increasing
      rates through the age group 20-30 followed by a decline. Change with age was not
      as evident among African and South American studies. Factors most often
      associated with the frequency of sexual intercourse were age, parity, duration of
      relationship, pregnancy, time, relationship status, fertility intentions, and
      contraception. CONCLUSIONS: There is variation in reported frequency of sexual
      intercourse between studies, age groups, and continents. Some of the variation
      may be due to variation in definitions, study designs, and methods suggesting a
      need for greater consistency in research practice.

PMID- 18086176
TI  - Restoration of the penis following amputation at circumcision: Shaeer's A-Y
      plasty.
AB  - INTRODUCTION: Male circumcision is one of the most commonly performed procedures
      worldwide. It has an estimated complication rate ranging from 0.1% to 35%.
      Amputation of the shaft is one of the most devastating complications reported,
      resulting from entrapment of the phallus between the blades of the clamp or from
      thermal injury due to the application of unipolar diathermy. AIM: In this work, I
      describe the guidelines I adopted in the management of 32 male patients afflicted
      with amputation of the shaft of the penis upon circumcision. METHODS: "Shaeer's A
      Y plasty" was performed for all patients, whereby the proximal corpora and crura
      were released from their attachment to the pubis and were advanced forward by
      insetting a specially configured fat flap into the resultant cavity. Skin grafts
      were used to cover the released penis. RESULTS: In all 32 cases, the released
      penis was within the normal range of penile length, and was cosmetically and
      functionally acceptable. CONCLUSIONS: "Shaeer's A-Y plasty" is capable of
      restoring the native phallus following amputation, with preservation of both
      gender identity and physiological characteristics of the penis to a large extent.

PMID- 18086177
TI  - Substitution rate of the hepatitis B virus surface gene.
AB  - Molecular epidemiology of hepatitis B virus (HBV) often relies on the comparison
      of HBV surface (S) gene sequences, although little is known about the
      substitution rate of the HBV S-gene. In this study, we compared HBV S-gene
      sequences in longitudinal sample pairs of 40 untreated, chronically HBV-infected
      patients, spanning 210 years of cumulative follow-up. The 40 patients included
      HBV e-antigen positive and negative persons; with HBV DNA levels ranging from
      10(3) to 10(9) cps/mL and belonging to HBV genotypes A, B, C, D and E. In the 40
      sample pairs, 70 nucleotide changes occurred in the HBV S-gene (0-8 per patient),
      resulting in an average substitution rate of 5.1 x 10(-4) nucleotide
      changes/site/year (range: 0-1.3 x 10(-2)). Surprisingly, the number of
      substitutions was strongly associated with the inverse level of viremia; and only
      weakly with the duration of follow-up: in 11 highly viremic patients (HBV DNA >
      or =10(8) cps/mL), only four substitutions occurred despite a cumulative
      observation period of 56 years (substitution rate: 1.1 x 10(-4)), while in the 10
      patients with viremia below 10(4) cps/mL, 29 substitutions occurred during 30
      years of follow-up (substitution rate: 14.6 x 10(-4)). We conclude that in
      chronic hepatitis B virus infection the rate of nucleotide substitution in the
      HBV S-gene is inversely related to the level of viremia and thus varies widely
      from person to person; hampering the phylogenetic analysis of possible chains of
      HBV infection.

PMID- 18086178
TI  - Hepatitis C virus core protein, lipid droplets and steatosis.
AB  - Lipid droplets are intracellular organelles involved not only in lipid storage
      but also in cell signalling and the regulation of intracellular vesicular
      trafficking. Recent basic studies have suggested that interactions between
      hepatitis C virus (HCV) core protein and lipid droplets are required for the HCV
      infection cycle. In infected cells, the HCV core protein is associated with the
      surface of lipid droplets and the endoplasmic reticulum membranes closely
      surrounding these droplets, and its self-assembly drives virion budding. This
      interaction also seems to be directly linked to a virus-induced steatosis, which
      involves the deposition of triglycerides in the liver and contributes to the
      progression of fibrosis in patients with chronic hepatitis C. Many clinical
      studies have reported that virus-induced steatosis is significantly more severe
      with HCV genotype 3 than with other genotypes, and this phenomenon has been
      modelled in recent basic studies based on the production of HCV core proteins of
      various genotypes in vitro. The association of HCV core protein with lipid
      droplets seems to play a central role in HCV pathogenesis and morphogenesis,
      suggesting that virus-induced steatosis may be essential for the viral life
      cycle.

PMID- 18086179
TI  - Wider indications for treatment of chronic hepatitis B?

PMID- 18086180
TI  - Efficacy of interferon plus ribavirin in the treatment of hepatitis C virus
      genotype 5.
AB  - Hepatitis C virus (HCV) genotype 5 has only been reported in a few countries and
      treatment response has not been well characterized. Our aim is to present the
      treatment outcome for HCV genotype 5 patients evaluated at three medical centres
      in Syria between January 2004 and June 2007. Medical records were reviewed
      retrospectively. Treatment consisted of ribavirin 1 000-1 200 mg daily plus
      interferon alpha-2a, 3 MU x 3/week or pegylated-interferon alpha-2a, 180
      mug/week. Patients were treated for 24 or 48 weeks. Sustained viral response
      (SVR) was assessed at the end of a 6-month follow-up period. Twenty-six treatment
      naive patients with HCV genotype 5 have completed the course of anti-HCV therapy
      and a 6-month follow-up. An SVR was achieved in 54% (47% with standard interferon
      and 67% with pegylated interferon, P = 0.43). A trend towards better results was
      observed for younger patients, low viremia and mild fibrosis. SVR was similar for
      treatment course of 24 or 48 weeks. In summary, treatment of HCV genotype 5 with
      combination therapy resulted in SVR in 54% of patients. Twenty-four weeks of
      treatment might be adequate. Further research should evaluate the ideal duration
      of treatment.

PMID- 18086181
TI  - Response rates to combination therapy for chronic HCV infection in a clinical
      setting and derivation of probability tables for individual patient management.
AB  - Evidence for efficacy of established treatment guidelines for chronic hepatitis C
      virus (HCV) disease is based on multinational randomized controlled trials
      (RCTs). Strategies for managing HCV, however, require an assessment of the
      effectiveness of intervention in routine clinical practice. We report the
      outcomes of combination therapy in a large cohort of HCV-infected individuals in
      the UK. A total of 347 (113 genotype 1, 234 genotype non-1) patients were treated
      with pegylated interferon and ribavirin according to current guidelines. Forty
      two (37.2%) of those with genotype 1 infection and 164 (70.1%) with genotype non
      1 infection achieved sustained viral response (SVR). Thirty-nine (11%) patients
      withdrew from treatment. In addition to viral genotype, factors predictive of a
      response to therapy were age at start of treatment and disease stage on
      pretreatment liver biopsy. Multivariate regression analysis demonstrated that the
      effects of age [odds ratio 0.5; 95% confidence interval (0.31-0.82) per 10-year
      increment (P = 0.006)] were confined to genotype 1 disease. In order to further
      inform the management of the individual patient, a multivariate logistic model
      was used to predict the probability of SVR for subgroups defined by disease
      stage, genotype and age at commencement of therapy. This model revealed striking
      differences in predicted response rates between subgroups and provided a strong
      rationale for early treatment, particularly for those with genotype 1 disease.
      Our study demonstrates that results comparable with those of RCTs can be achieved
      in clinical practice, and suggests that prediction of response rates based on
      probability modelling will provide a valuable adjunct to individual patient
      management.

PMID- 18086182
TI  - Increasing the uptake of hepatitis C virus testing among injecting drug users in
      specialist drug treatment and prison settings by using dried blood spots for
      diagnostic testing: a cluster randomized controlled trial.
AB  - The objective of this study was to assess whether introducing dried blood spot
      testing can increase hepatitis C virus (HCV) diagnostic testing. A cluster
      randomized controlled trial was conducted. Sites were matched into pairs, with
      one site in each pair randomly allocated to receive the intervention (training
      and use of dried blood spot). Data were collected from all sites for 6 months
      before and 6 months after the start of the intervention. The participants were 22
      specialist drug clinics and six prisons in England and Wales. The main outcome
      measure of this study was percentage point difference in individuals tested for
      HCV (the difference between the percentage of patients tested 6 months after and
      6 months before the introduction of dried blood spot tests). Before the trial, 8%
      of patients at control and intervention sites had been tested for HCV, with 16
      sites testing less than 5% of their caseload. The average percentage point
      difference between intervention and control sites was 14.5% (95% CI 1.3-28%,
      paired t-test, P = 0.03); with 13 of the 14 pairs contributing to the positive
      effect of the intervention (Wilcoxon matched-pairs signed-rank-test, P = 0.002).
      The size of the difference between intervention and control sites varied
      considerably. The study provides preliminary supporting evidence that dried blood
      spot testing may increase the uptake of HCV diagnostic testing, by increasing the
      opportunity for patients to be offered testing. Additional trials with a larger
      number of sites are justified, ideally in the context of drug and treatment
      policies that gave clearer priority (and targets) to infection control and
      testing.

PMID- 18086183
TI  - Osmiophilic bodies and the odd organelles of alveolates.
AB  - The apicomplexa are parasitic protozoa that are responsible for important human
      and animal diseases, including malaria, toxoplasmosis, cryptosporidiosis,
      coccidiosis and babesiosis. Like other members of the superphylum Alveolata,
      apicomplexans have regulated exocytosis of specialized secretory organelles, such
      as the apicomplexan-specific rhoptries and micronemes that are required for host
      cell invasion. The secretions of another class of organelles, the dense granules
      and osmiophilic bodies, are proposed to be required for maintenance of the
      parasitophorous vacuole and host cell egress. Little is known about the
      osmiophilic bodies and to date only one protein, P377, has been localized to this
      organelle. In this issue, de Koning-Ward et al. describe the disruption of pfg377
      in the virulent human malaria parasite, Plasmodium falciparum, which results in
      reduced osmiophilic body formation, a marked decrease in female fitness, and
      dramatically impaired infectivity to mosquitoes. These findings suggest that
      targeting PFG377 may be a strategy to block parasite transmission.

PMID- 18086184
TI  - Characterization of five novel Pseudomonas aeruginosa cell-surface signalling
      systems.
AB  - Cell-surface signalling is a sophisticated regulatory mechanism used by Gram
      negative bacteria to sense signals from outside the cell and transmit them into
      the cytoplasm. This regulatory system consists of an outer membrane-localized
      TonB-dependent receptor (TonB-dependent transducer), a cytoplasmic membrane
      localized antisigma factor and an extracytoplasmic function (ECF) sigma factor.
      Pseudomonas aeruginosa contains 13 potential surface signalling systems of which
      only six have been studied in detail. In this work we have identified the
      regulons of five novel P. aeruginosa signalling systems. For that, the ECF sigmas
      PA0149, PA1912, PA2050, PA2093 and PA4896 have been overexpressed and their
      target gene candidates have been identified using DNA microarray, proteomic
      analysis, and/or lacZ reporter construct. All five ECF sigma factors control the
      production of one TonB-dependent transducer. Interestingly, two sigma factors,
      PA2050 and PA2093, regulate the synthesis of a second transducer. Furthermore, we
      show that although all these sigma factors seem to control putative (metal)
      transport systems, one of them also regulates the expression of P. aeruginosa
      pyocins. Finally, we also show that the PA1912-PA1911-PA1910 (designated FemI
      FemR-FemA in this work) signalling system responds to the presence of the
      Mycobacterium siderophores mycobactin and carboxymycobactin and is involved in
      the utilization of these heterologous siderophores.

PMID- 18086185
TI  - Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers
      receptor dissociation.
AB  - Carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) are host
      receptors for the Dr family of adhesins of Escherichia coli. To define the
      mechanism for binding of Dr adhesins to CEACAM receptors, we carried out
      structural studies on the N-terminal domain of CEA and its complex with the Dr
      adhesin. The crystal structure of CEA reveals a dimer similar to other dimers
      formed by receptors with IgV-like domains. The structure of the CEA/Dr adhesin
      complex is proposed based on NMR spectroscopy and mutagenesis data in combination
      with biochemical characterization. The Dr adhesin/CEA interface overlaps
      appreciably with the region responsible for CEA dimerization. Binding kinetics,
      mutational analysis and spectroscopic examination of CEA dimers suggest that Dr
      adhesins can dissociate CEA dimers prior to the binding of monomeric forms. Our
      conclusions include a plausible mechanism for how E. coli, and perhaps other
      bacterial and viral pathogens, exploit CEACAMs. The present structure of the
      complex provides a powerful tool for the design of novel inhibitory strategies to
      treat E. coli infections.

PMID- 18086186
TI  - Division of labour during Bacillus subtilis biofilm formation.
AB  - Biofilms are multicellular aggregates of bacteria that are organized by an
      extracellular matrix. A key determinant of biofilm formation by a variety of
      bacteria is the proper regulation and assembly of the matrix components. In this
      issue of Molecular Microbiology, Chai et al. present the surprising finding that
      the genes encoding the components of the extracellular matrix in Bacillus
      subtilis are expressed in only a subpopulation of cells. Their results indicate
      that biofilms contain specialized cell types that are differentiated by
      transcriptional regulation. The population heterogeneity that they observe is
      another significant example in a growing list of phenotypes that arise owing to
      bistable gene expression.

PMID- 18086187
TI  - Undecaprenyl phosphate recycling comes out of age.
AB  - The recycling of the lipid carrier undecaprenyl-phosphate (Und-P) requires the
      dephosphorylation of Und-PP, a reaction proposed to occur at the external or
      periplasmic side of the bacterial cell membrane. In this issue of Molecular
      Microbiology, experiments based on the analysis of lipopolysaccharide
      modifications in Escherichia coli demonstrate that the phosphorylation of lipid A
      at position 1 is catalysed by the membrane enzyme LpxT (formerly YeiU). This
      enzyme specifically transfers the distal phosphate group from Und-PP to lipid A 1
      phosphate to produce lipid A 1-diphosphate. Furthermore, this reaction requires a
      functionally intact MsbA protein, which catalyses the transfer of lipid A across
      the membrane, confirming that the LpxT-mediated lipid A modification occurs on
      the periplasmic side of the membrane. These observations provide a novel and
      unexpected link between periplasmic lipid A modifications and the Und-PP
      recycling pathway.

PMID- 18086188
TI  - The Chlamydia outer membrane protein OmcB is required for adhesion and exhibits
      biovar-specific differences in glycosaminoglycan binding.
AB  - Chlamydia pneumoniae, an obligate intracellular human pathogen, causes a number
      of respiratory diseases. We explored the role of the conserved OmcB protein in C.
      pneumoniae infections, using yeast display technology. (i) Yeast cells presenting
      OmcB were found to adhere to human epithelial cells. (ii) Pre-incubation of OmcB
      yeast cells with heparin, but not other glycosaminoglycans (GAGs), abrogated
      adhesion. (iii) Pre-treatment of the target cells with heparinase inhibited
      adherence, and GAG-deficient CHO cell lines failed to bind OmcB yeast. (iv) A
      heparin-binding motif present near the N-terminus of OmcB is required for host
      cell binding. (v) Pre-treatment of chlamydial elementary bodies (EBs) with anti
      OmcB antibody or pre-incubation of target cells with recombinant OmcB protein
      reduced infectivity upon challenge with C. pneumoniae. (vi) Adhesion of
      fluorescently labelled EBs to epithelial or endothelial cells was abrogated by
      prior addition of heparin or OmcB protein. Thus, C. pneumoniae OmcB is an adhesin
      that binds heparan sulphate-like GAGs. OmcB from Chlamydia trachomatis serovar L1
      also adheres to human cells in a heparin-dependent way, unlike its counterpart
      from serovar E. We show that a single position in the OmcB sequence determines
      heparin dependence/independence, and variations there may reflect differences
      between the two serovars in cell tropism and disease pattern.

PMID- 18086190
TI  - Yarrowia lipolytica lipase production enhanced by increased air pressure.
AB  - AIMS: To study the cellular growth and morphology of Yarrowia lipolytica W29 and
      its lipase and protease production under increased air pressures. METHODS AND
      RESULTS: Batch cultures of the yeast were conducted in a pressurized bioreactor
      at 4 and 8 bar of air pressure and the cellular behaviour was compared with
      cultures at atmospheric pressure. No inhibition of cellular growth was observed
      by the increase of pressure. Moreover, the improvement of the oxygen transfer
      rate (OTR) from the gas to the culture medium by pressurization enhanced the
      extracellular lipase activity from 96.6 U l(-1) at 1 bar to 533.5 U l(-1) at 8
      bar. The extracellular protease activity was reduced by the air pressure
      increase, thereby eliciting further lipase productivity. Cell morphology was
      slightly affected by pressure, particularly at 8 bar, where cells kept the
      predominant oval form but decreased in size. CONCLUSIONS: OTR improvement by
      total air pressure rise up to 8 bar in a bioreactor can be applied to the
      enhancement of lipase production by Y. lipolytica. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Hyperbaric bioreactors can be successfully applied for yeast cells
      cultivation, particularly in high-density cultures used for enzymes production,
      preventing oxygen limitation and consequently increasing overall productivity.

PMID- 18086189
TI  - The role of osmiophilic bodies and Pfg377 expression in female gametocyte
      emergence and mosquito infectivity in the human malaria parasite Plasmodium
      falciparum.
AB  - Osmiophilic bodies are membrane-bound vesicles, found predominantly in Plasmodium
      female gametocytes, that become progressively more abundant as the gametocyte
      reaches full maturity. These vesicles lie beneath the subpellicular membrane of
      the gametocyte, and the release of their contents into the parasitophorous
      vacuole has been postulated to aid in the escape of gametocytes from the
      erythrocyte after ingestion by the mosquito. Currently, the only protein known to
      be associated with osmiophilic bodies in Plasmodium falciparum is Pfg377, a
      gametocyte-specific protein expressed at the onset of osmiophilic body
      development. Here we show by targeted gene disruption that Pfg377 plays a
      fundamental role in the formation of these organelles, and that female
      gametocytes lacking the full complement of osmiophilic bodies are significantly
      less efficient both in vitro and in vivo in their emergence from the erythrocytes
      upon induction of gametogenesis, a process whose timing is critical for
      fertilization with the short-lived male gamete. This reduced efficiency of
      emergence explains the significant defect in oocyst formation in mosquitoes fed
      blood meals containing Pfg377-negative gametocytes, resulting in an almost
      complete blockade of infection.

PMID- 18086191
TI  - Detection and quantification of Prymnesium parvum (Haptophyceae) by real-time
      PCR.
AB  - AIMS: The ichthyotoxic species Prymnesium parvum (Haptophyceae) is difficult to
      quantify in a microscopy-based monitoring programme, because the cells are very
      small, fragile and their morphology can be distorted by the use of fixatives. In
      the attempt to overcome these problems, a real-time PCR-based method for the
      rapid and sensitive identification and quantification of P. parvum was developed.
      METHODS AND RESULTS: A quantitative real-time PCR assay was optimized with
      primers designed on the internal transcribed spacer 2 rDNA region of P. parvum.
      This PCR assay was specific, showing no amplification of DNA extracted from
      closely related species, and sensitive. Moreover, this method was able to detect
      and reliably quantify P. parvum cells in preserved environmental samples
      artificially spiked with known amounts of cultured cells. CONCLUSIONS:
      Considering the specificity, sensitivity and applicability to preserved
      environmental samples, this method may be a useful tool for the monitoring of
      this toxic species. SIGNIFICANCE AND IMPACT OF THE STUDY: The real-time PCR
      method described in this study may represent a progress towards the rapid
      detection and quantification of P. parvum cells in water-monitoring programmes,
      allowing the early application of strategies to control bloom events, such as the
      use of clay minerals.

PMID- 18086192
TI  - Estimation of fungal growth using the ergosterol assay: a rapid tool in assessing
      the microbiological status of grains and feeds.
AB  - AIM: To use ergosterol assay as a rapid tool to assess the extent of fungal
      contamination in grains and feeds. METHODS AND RESULTS: Ergosterol was extracted
      from moulds and quantified using a modified method based on Seitz et al. (1977).
      A good correlation coefficient of 0.9998 was obtained for ergosterol standards
      and a strong correlation (R(2) = 0 x 9645) was established between the ergosterol
      content and the growth of Aspergillus niger ATCC 24126. This shows that this
      assay can be used to estimate fungal growth. The ergosterol contents and amount
      of carbon dioxide produced in both Control and Myco CURB (brand) liquid-treated
      corns were measured over 36 days. Ergosterol contents of pelleted pig feeds were
      also determined. In both experiments, the levels of ergosterol in the control
      samples were significantly higher than those of the mould-inhibitor-treated
      samples. CONCLUSIONS: A strong positive correlation (Spearman, Rs = 0 x 7241) was
      observed between the ergosterol content and the degree of fungal growth. Hence,
      ergosterol assay can be used as a rapid tool to assess the microbiological status
      of grains and feeds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study affirms
      that ergosterol assay is a rapid and accurate tool that can be used for the
      assessment of the feed quality.

PMID- 18086193
TI  - Fungal endophytes from Dioscorea zingiberensis rhizomes and their antibacterial
      activity.
AB  - AIMS: The aim of the study was to isolate and characterize the endophytic fungi
      from the rhizomes of the Chinese traditional medicinal plant Dioscorea
      zingiberensis and to detect their antibacterial activities. METHODS AND RESULTS:
      After strict sterile sample preparation, nine fungal endophytes were isolated
      from rhizomes of the Chinese traditional medicinal plant D. zingiberensis. The
      endophytes were classified by morphological traits and internal transcribed
      spacer (ITS) rRNA gene sequence analysis. Their ITS rDNA sequences were 99-100%
      identical to Nectria, Fusarium, Rhizopycnis, Acremonium and Penicillium spp.
      respectively. Of these, the most frequent genera were Fusarium and Nectria. One
      isolate, Dzf7, was unclassified on the basis of its low sequence similarity. The
      next closest species was Alternaria longissima (c. 92.4% sequence similarity).
      Endophyte isolate Dzf5 showed the closest sequence similarity (c. 99.5%) to an
      uncultured soil fungus (DQ420800) obtained from Cedar Creek, USA. Bioassays using
      a modified broth dilution test were used to detect the antibacterial activity of
      n-butanol extracts of both mycelia and culture filtrates of D. zingiberensis
      showed biological activity against Bacillus subtilis, Staphylococcus
      haemolyticus, Escherichia coli and Xanthomonas vesicatoria. Minimal inhibitory
      concentration (MIC) values of the extracts were between 31 x 25 microg ml(-1) and
      125 microg ml(-1). CONCLUSIONS: Endophytic fungus Dzf2 (c. 99 x 8% sequence
      similarity to Fusarium redolens) isolated from D. zingiberensis rhizome showed
      the most potent antibacterial activities. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Endophytic fungi isolated from D. zingiberensis may be used as potential
      producers of antibacterial natural products.

PMID- 18086194
TI  - Evaluation of the PCR method for identification of Bifidobacterium species.
AB  - AIMS: Bifidobacterium species are known for their beneficial effects on health
      and their wide use as probiotics. Although various polymerase chain reaction
      (PCR) methods for the identification of Bifidobacterium species have been
      published, the reliability of these methods remains open to question. METHODS AND
      RESULTS: In this study, we evaluated 37 previously reported PCR primer sets
      designed to amplify 16S rDNA, 23S rDNA, intergenic spacer regions, or repetitive
      DNA sequences of various Bifidobacterium species. CONCLUSIONS: Ten of 37
      experimental primer sets showed specificity for B. adolescentis, B. angulatum, B.
      pseudocatenulatum, B. breve, B. bifidum, B. longum, B. longum biovar infantis and
      B. dentium. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that
      published Bifidobacterium primer sets should be re-evaluated for both
      reproducibility and specificity for the identification of Bifidobacterium species
      using PCR. Improvement of existing PCR methods will be needed to facilitate
      identification of other Bifidobacterium strains, such as B. animalis, B.
      catenulatum, B. thermophilum and B. subtile.

PMID- 18086195
TI  - Rapid preparation of cyanobacterial DNA for real-time PCR analysis.
AB  - AIMS: To develop a rapid preparation method for real-time PCR analysis of
      cyanobacteria from cultures or field samples. METHODS AND RESULTS: Field samples
      and cultures containing Anabaena circinalis, Cylindrospermopsis raciborskii or
      Microcystis aeruginosa were subjected to three cell disruption treatments: (i)
      heating during thermocycling, (ii) microwave irradiation in the presence of
      detergent and (iii) probe sonication. Treated samples were directly added to the
      PCR reaction and analysed on two different real-time devices. A statistically
      significant difference was evident in the cycle thresholds for each of the
      treatments in all but one culture and one environmental sample, sonication and
      microwave treatments performing better than direct addition. The microwave
      treatment was also compared to the Qiagen DNA Mini kit and performance was
      equivalent when treated samples were analysed as above. CONCLUSIONS: Whilst
      microwave treatment was slightly less effective than probe sonication across all
      samples, it was more amenable to processing multiple samples and significantly
      better than heat treating the sample during thermocycling. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The microwave method described here is a simple, rapid and
      effective preparation method for cyanobacterial DNA that can be easily deployed
      in the field, making the most of the speed and flexibility offered by fixed and
      portable real-time PCR devices.

PMID- 18086196
TI  - Preliminary characterization of exopolysaccharides produced by a marine biofilm
      forming bacterium Pseudoalteromonas ruthenica (SBT 033).
AB  - AIM: The major objective of the present study was the partial characterization of
      the exopolysaccharides (EPS) produced by a marine biofilm-forming bacterium
      Pseudoalteromonas ruthenica under shake culture conditions. METHODS AND RESULTS:
      EPS-producing bacterial cultures were isolated from the sea water collected from
      the vicinity of coastal electric power station. Zobell marine broth medium was
      used for growth of the cultures and the EPS produced was quantified using phenol
      sulfuric acid method. Chemical characterization of the EPS was carried out using
      Fourier transform infrared spectroscopy (FTIR), and capillary gas chromatography
      (GC). Further, viscosity and rheological properties of the purified EPS were
      studied. The FTIR spectrum revealed prominent peaks of various groups of OH and
      CH(3) bending. GC analysis showed the presence of eight individual sugars.
      Rheological studies of the aqueous EPS showed good shearing property.
      CONCLUSIONS: Pseudoalteromonas ruthenica isolated from marine environment
      produced copious amount of EPS under shake culture conditions. GC analysis of the
      EPS revealed the presence of eight individual sugars and the EPS had good
      shearing property. SIGNIFICANCE AND IMPACT OF THE STUDY: The EPS produced by P.
      ruthenica is pseudoplastic in nature and is stable at higher pH levels. These
      properties suggest that the EPS may have potential applications in the oil,
      textiles and food industries.

PMID- 18086197
TI  - Evidence for widespread cryptic sexual generations in apparently purely asexual
      Andricus gallwasps.
AB  - Oak gallwasps (Hymenoptera, Cynipidae, Cynipini) are one of seven major animal
      taxa that commonly reproduce by cyclical parthenogenesis (CP). A major question
      in research on CP taxa is the frequency with which lineages lose their sexual
      generations, and diversify as purely asexual radiations. Most oak gallwasp
      species are only known from an asexual generation, and secondary loss of sex has
      been conclusively demonstrated in several species, particularly members of the
      holarctic genus Andricus. This raises the possibility of widespread secondary
      loss of sex in the Cynipini, and of diversification within purely parthenogenetic
      lineages. We use two approaches based on analyses of allele frequency data to
      test for cryptic sexual generations in eight apparently asexual European species
      distributed through a major western palaearctic lineage of the gallwasp genus
      Andricus. All species showing adequate levels of polymorphism (7/8) showed
      signatures of sex compatible with cyclical parthenogenesis. We also use DNA
      sequence data to test the hypothesis that ignorance of these sexual generations
      (despite extensive study on this group) results from failure to discriminate
      among known but morphologically indistinguishable sexual generations. This
      hypothesis is supported: 35 sequences attributed by leading cynipid taxonomists
      to a single sexual adult morphospecies, Andricus burgundus, were found to
      represent the sexual generations of at least six Andricus species. We confirm
      cryptic sexual generations in a total of 11 Andricus species, suggesting that
      secondary loss of sex is rare in Andricus.

PMID- 18086198
TI  - Can medical students from two cultures learn effectively from a shared web-based
      learning environment?
AB  - OBJECTIVE: This study aimed to establish whether medical students from 2
      different cultures can learn effectively from a shared web-based learning
      environment. METHODS: Students from the College of Medicine, Edinburgh, UK and
      the Medical School, Gifu, Japan shared 2 weeks of teaching and learning in
      clinical genetics, using problem-based learning in a web-based application (WBA).
      Questions about language, time zone, agreement about the curriculum (learning
      outcomes, tutor activity and assessment) and specific pedagogical issues about
      the educational effectiveness of students' learning were considered. RESULTS AND
      CONCLUSIONS: The evidence indicates that a shared WBA is practical where the
      learning outcomes and problem scenarios are common and students are fluent in the
      same language. Problem-based learning transfers itself best to online discussion
      boards when the numbers in the group are 16 or more. Students do not use the WBA
      as a primary source of resource material, and they augment the discussion boards
      with face-to-face meetings with peers and tutors.

PMID- 18086199
TI  - Recertifying as a doctor in Canada: international medical graduates and the
      journey from entry to adaptation.
AB  - OBJECTIVE: Globalisation and severe doctor shortages in many countries have
      resulted in increased numbers of international medical graduates (IMGs) in
      medical training programmes in major recipient countries such as Canada. Much of
      the literature on IMGs is written from the perspective of the doctor workforce.
      Less is known about the recertification training experiences of IMGs in recipient
      countries. This study aims to describe the recertification training experiences
      of IMGs in Canada in order to help medical training programmes understand how to
      facilitate the integration of IMGs into recipient medical communities. METHODS: A
      phenomenological (qualitative) research approach was undertaken for this study.
      International medical graduates undergoing recertification training in order to
      practise in Canada were individually interviewed about their experiences. Data
      collection and analysis followed the procedures of interpretive phenomenology.
      RESULTS: Twelve IMGs participated. Analysis of the interviews revealed 4 themes
      that typified IMG recertification training experiences: training entry barriers;
      and a 3-phase process of loss, disorientation and adaptation. International
      medical graduates must complete this 3-phase process in order to feel fully
      integrated into their professional environments. CONCLUSIONS: This study provided
      a description of IMGs' training experiences during certification for practice in
      Canada and revealed that these experiences were characterised by a 3-phase
      process of adjustment. Using this framework, a series of recommendations were
      proposed for medical training programmes to help IMGs with this process.

PMID- 18086200
TI  - Small mobile sequences in bacteria display diverse structure/function motifs.
AB  - Small repeat sequences in bacterial genomes, which represent non-autonomous
      mobile elements, have close similarities to archaeon and eukaryotic miniature
      inverted repeat transposable elements. These repeat elements are found in both
      intergenic and intragenic chromosomal regions, and contain an array of diverse
      motifs. These can include DNA sequences containing an integration host factor
      binding site and a proposed DNA methyltransferase recognition site, transcribed
      RNA secondary structural motifs, which are involved in mRNA regulation, and
      translated open reading frames found fused to other open reading frames. Some
      bacterial mobile element fusions are in evolutionarily conserved protein and RNA
      genes. Others might represent or lead to creation of new protein genes. Here we
      review the remarkable properties of these small bacterial mobile elements in the
      context of possible beneficial roles resulting from random insertions into the
      genome.

PMID- 18086201
TI  - Distinct regulators control the expression of methanol methyltransferase isozymes
      in Methanosarcina acetivorans C2A.
AB  - The mtaCB1, mtaCB2 and mtaCB3 operons encode isozymes of methanol
      methyltransferases in Methanosarcina acetivorans C2A and are among the most
      highly regulated genes known in Archaea. Here we identify cis and trans acting
      elements that affect the expression of these operons. In vivo reporter gene
      constructs expressed from sequentially truncated promoters show that the mRNA
      transcripts for these operons have large 5' untranslated regions. Regions
      upstream of the transcription start site (TSS) are important for induction of the
      mtaCB1 and mtaCB2 operons and for repression of the mtaCB3. Regions downstream of
      the TSS are important for expression of the mtaCB2 and mtaCB3 operons, but are
      dispensable for mtaCB1 expression. Proteins encoded by the MA0459 and MA0460 loci
      are required for induction of the mtaCB1 operon, while those encoded by MA4383,
      MA4397 and MA4398 are required for induction of mtaCB2. Proteins encoded by
      MA4397 and MA4398 are also required for methanol-specific repression of the
      mtaCB3 operon and, thus, are the first archaeal examples of regulatory proteins
      that simultaneously act in both repression and activation. We refer to these
      genes as methanol-specific regulators and designate MA0459, MA0460, MA4383,
      MA4397 and MA4398 as msrA, msrB, msrC, msrD and msrE respectively.

PMID- 18086202
TI  - The membrane-integrated transcriptional activator CadC of Escherichia coli senses
      lysine indirectly via the interaction with the lysine permease LysP.
AB  - In an acidic (pH 5.8) and lysine-rich environment Escherichia coli induces
      expression of the cadBA operon which encodes CadA, catalysing the decarboxylation
      of lysine to cadaverine, and CadB, the lysine/cadaverine antiporter. cadBA
      expression is dependent on CadC, a membrane-integrated transcriptional activator
      which belongs to the ToxR-like protein family and directly binds to the DNA in
      the cadBA promoter region. Here we describe that CadC senses the extracellular
      lysine not directly but indirectly requiring the interplay with the lysine
      permease LysP. Biochemical analyses of isolated CadC or the periplasmic domain of
      CadC (CadC188-512) revealed an unexpectedly low affinity for lysine, making it
      unlikely that CadC is a direct sensor for this substrate. Moreover, CadC hybrid
      proteins, in which the transmembrane domain or single amino acids were replaced,
      supported lysine-independent cadBA expression but retained a pH-dependent
      regulation. These CadC mutants were resistant to the effect of an overproduction
      of LysP, which represses cadBA expression in wild-type cells. Our results suggest
      a model according to which CadC is inactivated by an interaction with LysP at a
      low external lysine concentration. When lysine is abundantly available, the
      interaction between LysP and CadC is released, and CadC becomes susceptible to
      activation by low pH.

PMID- 18086203
TI  - Rhizobium common nod genes are required for biofilm formation.
AB  - In legume nitrogen-fixing symbioses, rhizobial nod genes are obligatory for
      initiating infection thread formation and root nodule development. Here we show
      that the common nod genes, nodD1ABC, whose products synthesize core Nod factor, a
      chitin-like oligomer, are also required for the establishment of the three
      dimensional architecture of the biofilm of Sinorhizobium meliloti. Common nod
      gene mutants form a biofilm that is a monolayer. Moreover, adding Nod Factor
      antibody to S. meliloti cells inhibits biofilm formation, while chitinase
      treatment disrupts pre-formed biofilms. These results attest to the involvement
      of core Nod factor in rhizobial biofilm establishment. However, luteolin, the
      plant-derived inducer of S. meliloti's nod genes, is not required for mature
      biofilm formation, although biofilm establishment is enhanced in the presence of
      this flavonoid inducer. Because biofilm formation is plant-inducer-independent
      and because all nodulating rhizobia, both alpha- and beta-proteobacteria have
      common nod genes, the role of core Nod factor in biofilm formation is likely to
      be an ancestral and evolutionarily conserved function of these genes.

PMID- 18086204
TI  - Dynein-dynactin complex subunits are differentially localized in brain and spinal
      cord, with selective involvement in pathological features of neurodegenerative
      disease.
AB  - AIMS: The dynein-dynactin complex, mostly recognized for axonal retrograde
      transport in neurones, has an ever growing list of essential subcellular
      functions. Here, the distribution of complex subunits in human central nervous
      system (CNS) has been assessed using immunohistochemistry in order to test the
      hypothesis that this may be altered in neurodegenerative disease. METHODS: Three
      dynactin and two dynein subunits were immunolocalized in the CNS of human post
      mortem sections from motor neurone disease, Alzheimer's disease and patients with
      no neurological disease. RESULTS: Unexpectedly, coordinated distribution of
      complex subunits was not evident, even in normal tissues. Complex subunits were
      differentially localized in brain and spinal cord, and localization of certain
      subunits, but not others, occurred in pathological structures of motor neurone
      and Alzheimer's diseases. CONCLUSIONS: These results suggest that dynein-dynactin
      complex subunits may have specific subcellular roles, and primary events that
      disturb the function of individual components may result in disequilibrium of
      subunit pools, with the possibility that availability for normal cytoplasmic
      functions becomes impaired, with consequent organelle and axonal transport
      misfunction.

PMID- 18086205
TI  - Association between changes in symptoms and gastric emptying in gastroparetic
      patients treated with gastric electrical stimulation.
AB  - To investigate whether there is an association between gastric emptying rate and
      symptom improvement in gastroparetic patients treated with gastric electrical
      stimulation (GES), we retrospectively reviewed 63 gastroparetic patients who
      received GES therapy for at least 1 year. Patient characteristics, seven upper
      gastrointestinal (GI) symptoms and 4-h standardized gastric emptying test (GET)
      were evaluated at baseline and at 1 year of GES. All symptoms were significantly
      reduced (P < 0.001). Mean gastric retention was reduced by 7% (P = 0.102) for
      measurement at 4 h. Of the 63 patients, 14 had their GET normalized and 49
      remained delayed after 1 year. Normalized GET patients had a similar symptom
      improvement as those whose GET remained delayed. Of all upper GI symptoms, the
      improvements in vomiting (P = 0.04), nausea (P = 0.002) and epigastric pain (P =
      0.001) were significantly correlated with reduction in 4-h gastric retention
      between baseline and 12 months of GES therapy for patients with normalized
      gastric emptying but there were no correlations with any symptoms and change in
      gastric emptying for those patients who remained delayed. In summary, overall
      gastric emptying is not significantly accelerated at 4 h after successful
      symptomatic improvement with GES but nausea, vomiting and epigastric pain can be
      correlated with normalization of GET in a subset of patients.

PMID- 18086206
TI  - Targets of myenteric interneurons in the guinea-pig small intestine.
AB  - Polarized outputs of myenteric interneurons in guinea-pig small intestine have
      been well studied. However, the variety of motility patterns exhibited suggests
      that some interneuron targets remain unknown. We used antisera selected to
      distinguish interneuron varicosities and known myenteric neuron types to
      investigate outputs of three interneuron classes in guinea-pig jejunum; two
      classes of descending interneurons immunoreactive (IR) for somatostatin (SOM) or
      nitric oxide synthase (NOS)/vasoactive intestinal peptide (VIP), and one class of
      ascending interneurons [calretinin/enkephalin (ENK)-IR]. Varicosities apposed to
      immunohistochemically identified cell bodies were quantified by confocal
      microscopy. Intrinsic sensory neurons (calbindin-IR) were apposed by few
      varicosities. Cholinergic secretomotor neurons (neuropeptide Y-IR) were apposed
      by many SOM-IR varicosities. Longitudinal muscle excitatory motor neurons
      (calretinin-IR) were apposed by some VIP- and ENK-IR varicosities, but few SOM-IR
      varicosities. Ascending interneurons (calretinin-IR) were apposed by many
      varicosities of all types. NOS-IR interneurons and inhibitory motor neurons were
      apposed by numerous VIP-IR and SOM-IR varicosities. NOS-IR short inhibitory motor
      neurons were apposed by significantly fewer ENK-IR varicosities than other NOS-IR
      neurons. Based on the specific chemical coding of ascending (ENK) and descending
      (SOM) interneurons, we conclude that cholinergic secretomotor neurons and short
      inhibitory neurons are located in descending reflex pathways, while ascending
      interneurons and NOS-IR descending interneurons are focal points at which
      ascending and descending pathways converge.

PMID- 18086207
TI  - The role of somatosensory cortical regions in the processing of painful gastric
      fundic distension: an update of brain imaging findings.
AB  - Painful gastric distension is processed in a network consisting of brainstem,
      thalamus, insula, anterior cingulate cortex, (lateral) orbitofrontal and
      prefrontal cortex, superior temporal cortex and cerebellum. However, the role of
      primary and secondary somatosensory cortical regions (SI/SII) in the processing
      of visceral sensation or pain in general and gastric sensation in particular
      remains unclear. The aim of this study was to localize activations in the SI/SII
      area from our previously published functional brain imaging studies on gastric
      distension more precisely, using newly available cytoarchitectonic probability
      maps of SI/SII, implemented in the SPM Anatomy toolbox. In healthy volunteers, we
      found two clusters to be overlapping with SII (mainly the OP4 subregion) and, to
      a lesser extent, SI, although this overlap was small in size. In functional
      dyspepsia patients, we found two clusters to be overlapping with SII (mainly
      OP4), of which the cluster in the right hemisphere also overlapped with SI. These
      findings were confirmed in a conjunction analysis of both groups. Activation in
      right SI/SII was significantly higher in healthy volunteers when formally
      compared to patients. These results provide more detailed information on the
      brain processing of gastric sensation, supporting the hypothesis that SI/SII are
      involved. This is in line with some previously published studies on visceral
      sensation, but at variance with some other studies. Methodological differences
      between the brain imaging studies on gastric distension may account for these
      somewhat discrepant findings.

PMID- 18086208
TI  - Strain measurement during antral contractions by ultrasound strain rate imaging:
      influence of erythromycin.
AB  - Strain rate imaging (SRI) is a non-invasive ultrasound (US) modality that enables
      the study of mechanical deformation (strain) with high spatial and temporal
      resolution. A total of 244 contractions in seven healthy volunteers were studied
      by SRI on two separate days to characterize radial strain of antral contractions
      in the fasting and fed states and to assess the influence of intravenous
      erythromycin. Gastric accommodation and emptying were assessed by 2D
      ultrasonography. The perception of hunger was registered by the participants. The
      strain increased from early to late phase II and phase III activity by (median)
      18%, 58% and 82%, respectively, P < 0.05. Erythromycin infusion in phase I
      induced contractions with median strain of 35%, but did not increase postprandial
      strain. Both fasting and postprandially, lumen-occlusive contractions with
      erythromycin were more frequent than in naturally occurring contractions, 69%vs
      48%, P = 0.036 and 40%vs 5%, P < 0.001 respectively. All subjects had rumbling in
      their abdomens when intraluminal air was detected sonographically (85% of all
      phase III contractions) and that rumbling was perceived by the participant as
      maximal awareness of hunger. SRI enabled detailed strain measurement of
      individual antral contractions. Erythromycin initiated fasting antral
      contractions and increased the number of lumen-occlusive contractions.

PMID- 18086209
TI  - Deletion of the archaeal histone in Methanosarcina mazei Go1 results in reduced
      growth and genomic transcription.
AB  - HMm is the only archaeal histone in Methanosarcina mazei Gol and recombinant HMm,
      synthesized by expression of MM1825 in Escherichia coli, has been purified and
      confirmed to have the DNA binding and compaction properties characteristic of an
      archaeal histone. Insertion of a puromycin resistance conferring cassette (pac)
      into MM1825 was not lethal but resulted in mutants (M. mazei MM1825::pac) that
      have impaired ability to grow on methanol and trimethylamine. Loss of HMm also
      resulted in increased sensitivity to UV light and decreased transcript levels for
      approximately 25% of all M. mazei genes. For most genes, the transcript decrease
      was 3- to 10-fold, but transcripts of MM483 (small heat-shock protein), MM1688
      (trimethylamine:corrinoid methyl transferase) and MM3195 (transcription
      regulator), were reduced 100-, 100- and 25-fold, respectively, in M. mazei
      MM1825::pac cells. Transcripts of only five adjacent genes that appear to
      constitute an aromatic amino acid biosynthetic operon were elevated in M. mazei
      MM1825::pac cells. Complementary synthesis of HMm from a plasmid transformed into
      M. mazei MM1825::pac restored wild-type growth and transcript levels.

PMID- 18086210
TI  - SaPI mutations affecting replication and transfer and enabling autonomous
      replication in the absence of helper phage.
AB  - The SaPIs are chromosomal islands in staphylococci and other Gram-positive
      bacteria that carry genes for superantigens, virulence factors, resistance and
      certain metabolic functions. They have intimate relationships with certain
      temperate phages involving phage-induced excision, replication and efficient
      packaging in special small-headed infective phage-like particles, resulting in
      very high transfer frequencies. They generally contain 18-22 ORFs. We have
      systematically inactivated each of these ORFs and determined their functional
      groupings. In other reports, we have shown that five are involved in
      excision/integration, replication and packaging. In this report, we summarize the
      mutational analysis and focus on two key ORFs involved in regulation of the SaPI
      excision-replication-packaging cycle vis-a-vis phage induction. These two genes
      are divergently transcribed and define the major transcriptional organization of
      the SaPI genome. One of them, stl, encodes a master repressor, possibly analogous
      to the standard cI phage repressor. Mutational inactivation of this gene results
      in SaPI excision and replication in the absence of any inducing phage. This
      replicated SaPI DNA is not packaged; however, since the capsid components are
      provided by the helper phage. We have not yet ascertained any specific function
      for the second putative regulatory gene, though it is highly conserved among the
      SaPIs.

PMID- 18086211
TI  - DivS, a novel SOS-inducible cell-division suppressor in Corynebacterium
      glutamicum.
AB  - DNA damage-induced SOS response elicits the induction of cell-division suppressor
      as well as DNA repair genes. In Gram-positive bacteria, cell-division suppressor
      genes, so far characterized from Bacillus subtilis (yneA) and Mycobacterium
      tuberculosis (rv2719c), share limited homology, but are both located in the
      vicinity of lexA on their respective genomes. Using this proximity to lexA,
      Corynebacterium glutamicum R divS (cgR1759) was identified as an SOS-inducible
      cell-division suppressor in this study. The amino acid sequence of DivS showed no
      homology to that of YneA and Rv2719c. divS expression was markedly induced by DNA
      damaging mitomycin C treatment in wild-type cells, but not in its DeltarecA
      mutant cells, which are unable to induce the SOS response. Wild-type C.
      glutamicum R cells exposed to DNA-damaging mitomycin C exhibited elongated
      morphology that, using green fluorescent protein-FtsZ fusion protein, was
      attributed to defects in FtsZ ring assembly. Cells defective in FtsZ ring
      assembly were subsequently incapable of septum wall synthesis. In the presence of
      mitomycin C, divS mutant cells did not exhibit this elongated morphology, whereas
      cells overexpressing divS were elongated and abnormally branched.

PMID- 18086212
TI  - ppGpp and DksA likely regulate the activity of the extracytoplasmic stress factor
      sigmaE in Escherichia coli by both direct and indirect mechanisms.
AB  - One of the major signalling pathways responsible for intercompartmental
      communication between the cell envelope and cytoplasm in Escherichia coli is
      mediated by the alternative sigma factor, sigmaE. sigmaE has been studied
      primarily for its role in response to the misfolding of outer membrane porins.
      This response is essentially reactionary; cells are stressed, porin folding is
      disrupted, and the response is activated. sigmaE can also be activated following
      starvation for a variety of nutrients by the alarmone ppGpp. This response is
      proactive, as sigmaE is activated in the absence of any obvious damage to the
      cell envelope sensed by the stress signalling pathway. Here we examine the
      mechanism of regulation of sigmaE by ppGpp. ppGpp has been proposed to activate
      at least two alternative sigma factors, sigmaN and sigmaS, indirectly by altering
      the competition for core RNA polymerase between the alternative sigma factors and
      the housekeeping sigma factor, sigma70. In vivo experiments with sigmaE are
      consistent with this model. However, ppGpp and its cofactor DksA can also
      activate transcription by EsigmaEin vitro, suggesting that the effects of ppGpp
      on sigmaE activity are both direct and indirect.

PMID- 18086213
TI  - Trigger enzymes: bifunctional proteins active in metabolism and in controlling
      gene expression.
AB  - All regulatory processes require components that sense the environmental or
      metabolic conditions of the cell, and sophisticated sensory proteins have been
      studied in great detail. During the last few years, it turned out that enzymes
      can control gene expression in response to the availability of their substrates.
      Here, we review four different mechanisms by which these enzymes interfere with
      regulation in bacteria. First, some enzymes have acquired a DNA-binding domain
      and act as direct transcription repressors by binding DNA in the absence of their
      substrates. A second class is represented by aconitase, which can bind iron
      responsive elements in the absence of iron to control the expression of genes
      involved in iron homoeostasis. The third class of these enzymes is sugar
      permeases of the phosphotransferase system that control the activity of
      transcription regulators by phosphorylating them in the absence of the specific
      substrate. Finally, a fourth class of regulatory enzymes controls the activity of
      transcription factors by inhibitory protein-protein interactions. We suggest that
      the enzymes that are active in the control of gene expression should be
      designated as trigger enzymes. An analysis of the occurrence of trigger enzymes
      suggests that the duplication and subsequent functional specialization is a major
      pattern in their evolution.

PMID- 18086214
TI  - Maturation of Streptococcus pneumoniae lipoproteins by a type II signal peptidase
      is required for ABC transporter function and full virulence.
AB  - Cell surface lipoproteins are important for the full virulence of several
      bacterial pathogens, including Streptococcus pneumoniae. Processing of
      prolipoproteins seems to be conserved among different bacterial species, and
      requires type II signal peptidase (Lsp) mediated cleavage of the N-terminal
      signal peptide to form the mature lipoprotein. Lsp has been suggested as a target
      for new antibiotic therapies, but at present there are only limited data on the
      function of Lsp for Gram-positive bacterial pathogens. We have investigated the
      function and role during disease pathogenesis of the S. pneumoniae Lsp, which,
      blast searches suggest, is encoded by the gene Sp0928. Expression of Sp0928
      protected Escherichia coli against the Lsp antagonist globomycin, and proteomics
      and immunoblot analysis demonstrated that deletion of Sp0928 prevented processing
      of S. pneumoniae prolipoproteins to mature lipoproteins. These data strongly
      suggest that Sp0928 encodes the S. pneumoniae Lsp. However, immunoblots of
      membrane-associated proteins, immunoelectron microscopy and flow cytometry assays
      all confirmed that in the absence of Lsp, immature lipoproteins were still
      attached to the cell surface. Despite preservation of lipoprotein attachment to
      the cell membrane, loss of S. pneumoniae Lsp resulted in several phenotypes
      associated with impaired lipoprotein function and reduced S. pneumoniae
      replication in animal models of infection.

PMID- 18086215
TI  - A bifunctional DNA binding region in Tn5 transposase.
AB  - Tn5 transposition is a complicated process that requires the formation of a
      highly ordered protein-DNA structure, a synaptic complex, to catalyse the
      movement of a sequence of DNA (transposon) into a target DNA. Much is known about
      the structure of the synaptic complex and the positioning of protein-DNA
      contacts, although many protein-DNA contacts remain largely unstudied. In
      particular, there is little evidence for the positioning of donor DNA and target
      DNA. In this communication, we describe the isolation and analysis of mutant
      transposases that have, for the first time, provided genetic and biochemical
      evidence for the stage-specific positioning of both donor and target DNAs within
      the synaptic complex. Furthermore, we have provided evidence that some of the
      amino acids that contact donor DNA also contact target DNA, and therefore suggest
      that these amino acids help define a bifunctional DNA binding region responsible
      for these two transposase-DNA binding events.

PMID- 18086216
TI  - Reported pertussis infection and risk of atopy in 8- to 12-yr-old vaccinated and
      non-vaccinated children.
AB  - Pertussis infection has been suspected to be a potential causal factor in the
      development of atopic disease because of the effect of pertussis immunization on
      specific IgE antibodies. Although several studies found a positive association
      between pertussis infection and atopic disorders, this relationship has not yet
      been studied in a population stratified by vaccination status. To assess the
      association between pertussis infection and atopic disorders in pertussis
      unvaccinated children and in pertussis-vaccinated children. Using data from a
      previously conducted study on the relationship between the diphtheria-tetanus
      pertussis-(inactivated) poliomyelitis vaccination in the first year of life and
      atopic disorders, the study population of 1872 8-12 yr old was divided into
      children pertussis-unvaccinated and children pertussis-vaccinated in the first
      year of life. Within each group, the association between pertussis infection and
      atopic disorders (both as reported by the parents) was assessed. In the
      unvaccinated group, there were no significant associations between pertussis
      infection and atopic disorders. In the vaccinated group, all associations between
      pertussis infection and atopic disorders were positive, the associations with
      asthma [odds ratio (OR) = 2.24, 95% confidence interval (CI(95%)): 1.36-3.70],
      hay fever (OR = 2.35, CI(95%): 1.46-3.77) and food allergy (OR = 2.68, CI(95%):
      1.48-4.85) being significant. There was a positive association between pertussis
      infection and atopic disorders in the pertussis vaccinated group only. From the
      present study, it cannot be concluded whether this association is causal or due
      to reverse causation.

PMID- 18086217
TI  - The effect of digestion and pH on the allergenicity of kiwifruit proteins.
AB  - It is suggested that patients with oral allergy syndrome (OAS) respond to pepsin
      sensitive allergens, and systemic reactors identify pepsin-resistant allergens.
      We sought to assess the digestibility of kiwifruit proteins in simulated gastric
      fluid (SGF), and to compare the immunogenicity of the digests in patients with
      isolated oral and systemic reactions to kiwifruit. In addition, the effect of pH
      on digestibility of kiwifruit proteins was investigated. The in vitro resistance
      of kiwifruit proteins to digestion was determined using SGF. G-immunoglobulin
      (IgE) binding to digested proteins was investigated by Western blotting using
      sera from children and adults (aged 5-72 yr) with systemic reactions and patients
      with isolated oral symptoms. To determine whether pH conditions influence
      digestion of kiwifruit extracts, digestion at pHs 1.5-7 were compared by SDS
      PAGE. Patients with systemic reactions showed IgE binding to digestion-resistant
      allergens, but patients with oral symptoms reacted only to digestion-labile
      allergens. An increase in pH from 1.5 to 2.5 significantly reduced pepsin
      breakdown of kiwifruit allergens. Immunoreactive digested protein fragments were
      detectable by immunoblot but not Coomassie stain. This study confirms a
      difference in the lability of food allergens recognized by patients with systemic
      reactions and those with OAS. Pepsin digestion of kiwifruit proteins was impaired
      by hypoacidic conditions suggesting that patients with hypoacidic gastric
      conditions are at increased risk of systemic absorption of allergens. The data
      indicate that commonly used methods for predicting allergenicity of novel
      proteins using Coomassie stains may be flawed.

PMID- 18086218
TI  - Effects of feeding probiotics during weaning on infections and antibody responses
      to diphtheria, tetanus and Hib vaccines.
AB  - Microbial exposure is necessary for the development of normal immune function,
      which has driven the idea of using probiotics for treatment and prevention of
      immune-mediated diseases in infancy and childhood. Mounting evidence indicates
      that probiotics have immunomodulatory effects. However, the mechanisms are still
      poorly understood. Specific antibody response is a valuable proxy for immune
      system maturation status in infancy. We aimed at determining the impact of
      Lactobacillus F19 (LF19) during weaning on infections and IgG antibody responses
      to routine vaccines. In a double-blind, placebo-controlled randomized
      intervention trial, infants were fed cereals with (n = 89) or without LF19 (n =
      90) from 4 to 13 months of age. Infants were immunized with DTaP (diphtheria and
      tetanus toxoid and acellular pertussis), polio and Hib-conjugate vaccines at (3),
      5(1/2) and 12 months of age. We assessed the number of days with infections,
      antibiotic prescriptions and antibody concentrations to Hib capsular
      polysaccharide (HibPS), diphtheria toxin (D) and tetanus toxoid (T) before and
      after the second and third doses. Days with infectious symptoms did not differ
      between the groups. Days with antibiotic prescriptions were fewer in the LF19
      group (p = 0.044). LF19 enhanced anti-D concentrations when adjusting for
      breastfeeding duration and colonization with LF19 (p = 0.024). There was an
      interaction of the intervention and colonization with LF19 on anti-T
      concentrations during the course of vaccination (p = 0.035). The anti-HibPS
      concentrations were higher after the first and second dose of Hib vaccine in
      infants breastfed <6 months compared with those breastfed > or =6 months (p <
      0.05), with no effect by LF19. In conclusion, feeding LF19 did not prevent
      infections, but increased the capacity to raise immune responses to protein
      antigens, with more pronounced effects in infants breastfed <6 months.

PMID- 18086219
TI  - Food hypersensitivity among Caucasian and non-Caucasian children.
AB  - There are little data regarding the frequency of different foods that cause
      hypersensitivity in the UK. Furthermore, there are no data regarding food
      hypersensitivity related to ethnic variations. This prospective study involved 76
      children with IgE-mediated food allergy presenting consecutively over 18 months
      to a Paediatric Allergy Clinic serving a well-defined population that is 21% non
      Caucasian. A total of 52.6% of the paediatric allergy clinic population was non
      Caucasian compared with 35.9% in General Paediatric Clinics giving a mean
      difference in percentage of 16.7 (5.6, 27.8), p < 0.01. The average number of
      food allergens per child in the non-Caucasian group was 2.05 vs. 1.22 in the
      Caucasian group, mean difference 0.83, which is significant (t = 4.15, d.f. = 74,
      p < 0.01). Analysis of other allergic conditions revealed no significant increase
      in the non-Caucasian group. The mean age of first reaction to any food was 2.6 yr
      (range 0.3-12 yr) in Caucasian, and 1.7 yr (range 0.3-8 yr) in non-Caucasian,
      children (p < 0.05). There were 125 reactions in the study population, with egg,
      peanut, tree nut, cow milk and cod being the commonest food allergens. Some novel
      foods, such as kiwi, lentil and sesame, were also represented in the top 10 food
      allergies, particularly in the non-Caucasian population. Ethnic minorities are
      over-represented in terms of the number of children with food allergy and number
      of food allergies per child, present at an earlier age with food allergy, and
      possibly have a greater variety of food allergies compared with Caucasians. This
      is important in terms of health education. Our findings need confirmation by a
      more detailed population based study, ideally using food challenges in addition
      to history and skin prick testing.

PMID- 18086220
TI  - Root inoculation with a forest soil streptomycete leads to locally and
      systemically increased resistance against phytopathogens in Norway spruce.
AB  - Soil streptomycetes are commonly antagonistic against plant pathogens. However,
      interactions involving increased defense responses in the host plant, leading to
      suppression of plant disease development, have not yet been detailed. Here, the
      mechanisms were studied of disease suppression by Streptomyces sp. GB 4-2 against
      Heterobasidion root and butt rot in Norway spruce (Picea abies) seedlings. GB 4-2
      promoted mycelial growth of the phytopathogenic fungus, germination rate of
      fungal spores, extension of germ tubes and early colonization of outer cortical
      layers of the plant root. Reduced colonization of the inner cortical cell layers
      was accompanied by the induction of cell wall appositions, and increased xylem
      formation in the vascular cylinder emerged after bacterium-fungus coinoculation.
      Bacterial treatment led to decreased water content in roots and needles and
      increased photosynthetic yield (F(v)/F(m)) and peroxidase activities in needles.
      The infection of needles by Botrytis cinerea was reduced by bacterial
      pretreatment. Complex interactions of GB 4-2 with Norway spruce and
      Heterobasidion abietinum were discovered. The bacterium promoted the growth of
      the phytopathogenic fungus but induced plant defense responses. Host responses
      indicate that GB 4-2 induces both local and systemic defense responses in Norway
      spruce.

PMID- 18086221
TI  - Internal transcribed spacer primers and sequences for improved characterization
      of basidiomycetous orchid mycorrhizas.
AB  - Despite advances owing to molecular approaches, several hurdles still obstruct
      the identification of fungi forming orchid mycorrhizas. The Tulasnellaceae
      exhibit accelerated evolution of the nuclear ribosomal operon, causing most
      standard primers to fail in polymerase chain reaction (PCR) trials. Insufficient
      sequences are available from well characterized isolates and fruitbodies. Lastly,
      taxon-specific PCR primers are needed in order to explore the ecology of the
      fungi outside of the orchid root. Here, progress in overcoming these hurdles is
      reported. Broad-spectrum basidiomycete internal transcribed spacer (ITS) primers
      that do not exclude most known Tulasnellaceae are presented. blast searches and
      empirical PCR tests support their wide utility within the Basidiomycota. Taxon
      specific ITS primers are presented targeted to orchid-associated Tulasnella, and
      a core component of the Thelephora-Tomentella complex. The efficiency and
      selectivity of these primer sets are again supported by blast searches and
      empirical tests. Lastly, ITS DNA sequences are presented from several strains of
      Epulorhiza, Ceratorhiza, Ceratobasidium, Sistotrema, Thanatephorus and Tulasnella
      that were originally described in the landmark mycorrhizal studies of Currah and
      Warcup. Detailed phylogenetic analyses reveal some inconsistencies in species
      concepts in these taxonomically challenging resupinate basidiomycetes, but also
      help to place several sequences from environmental samples.

PMID- 18086222
TI  - Underwater photosynthesis and respiration in leaves of submerged wetland plants:
      gas films improve CO2 and O2 exchange.
AB  - Many wetland plants have gas films on submerged leaf surfaces. We tested the
      hypotheses that leaf gas films enhance CO(2) uptake for net photosynthesis (P(N))
      during light periods, and enhance O(2) uptake for respiration during dark
      periods. Leaves of four wetland species that form gas films, and two species that
      do not, were used. Gas films were also experimentally removed by brushing with
      0.05% (v/v) Triton X. Net O(2) production in light, or O(2) consumption in
      darkness, was measured at various CO(2) and O(2) concentrations. When gas films
      were removed, O(2) uptake in darkness was already diffusion-limited at 20.6 kPa
      (critical O(2) pressure for respiration, COP(R)>/= 284 mmol O(2) m(-3)), whereas
      for some leaves with gas films, O(2) uptake declined only at approx. 4 kPa
      (COP(R) 54 mmol O(2) m(-3)). Gas films also improved CO(2) uptake so that, during
      light periods, underwater P(N) was enhanced up to sixfold. Gas films on submerged
      leaves enable continued gas exchange via stomata and thus bypassing of cuticle
      resistance, enhancing exchange of O(2) and CO(2) with the surrounding water, and
      therefore underwater P(N) and respiration.

PMID- 18086223
TI  - Functional analysis of the Arabidopsis PHT4 family of intracellular phosphate
      transporters.
AB  - The transport of phosphate (Pi) between subcellular compartments is central to
      metabolic regulation. Although some of the transporters involved in controlling
      the intracellular distribution of Pi have been identified in plants, others are
      predicted from genetic, biochemical and bioinformatics studies. Heterologous
      expression in yeast, and gene expression and localization in plants were used to
      characterize all six members of an Arabidopsis thaliana membrane transporter
      family designated here as PHT4. PHT4 proteins share similarity with SLC17/type I
      Pi transporters, a diverse group of animal proteins involved in the transport of
      Pi, organic anions and chloride. All of the PHT4 proteins mediate Pi transport in
      yeast with high specificity. Bioinformatic analysis and localization of PHT4-GFP
      fusion proteins indicate that five of the proteins are targeted to the plastid
      envelope, and the sixth resides in the Golgi apparatus. PHT4 genes are expressed
      in both roots and leaves, although two of the genes are expressed predominantly
      in leaves and one mostly in roots. These expression patterns, together with Pi
      transport activities and subcellular locations, suggest roles for PHT4 proteins
      in the transport of Pi between the cytosol and chloroplasts, heterotrophic
      plastids and the Golgi apparatus.

PMID- 18086224
TI  - The observer effect in plant science.

PMID- 18086225
TI  - Two allopolyploid ascomycete fungal plant pathogens were not rescued by vertical
      transmission.

PMID- 18086226
TI  - Bacterial mycophagy: definition and diagnosis of a unique bacterial-fungal
      interaction.
AB  - This review analyses the phenomenon of bacterial mycophagy, which we define as a
      set of phenotypic behaviours that enable bacteria to obtain nutrients from living
      fungi and thus allow the conversion of fungal into bacterial biomass. We
      recognize three types of bacterial strategies to derive nutrition from fungi:
      necrotrophy, extracellular biotrophy and endocellular biotrophy. Each is
      characterized by a set of uniquely sequential and differently overlapping
      interactions with the fungal target. We offer a detailed analysis of the nature
      of these interactions, as well as a comprehensive overview of methodologies for
      assessing and quantifying their individual contributions to the mycophagy
      phenotype. Furthermore, we discuss future prospects for the study and
      exploitation of bacterial mycophagy, including the need for appropriate tools to
      detect bacterial mycophagy in situ in order to be able to understand, predict and
      possibly manipulate the way in which mycophagous bacteria affect fungal activity,
      turnover, and community structure in soils and other ecosystems.

PMID- 18086227
TI  - Laticifers and secretory ducts: two other tube systems in plants.
AB  - The plant kingdom has elaborated several conducting systems. Three are primarily
      for mass transport: the aerenchyma (for gas exchange in submerged parts), the
      phloem (for exchange of nutrients within the plant), and the xylem (largely for
      transport of water from soil to transpiring leaves). Two others are believed to
      be primarily defensive and to store under pressure aversive contents which they
      exude when punctured: the laticifer and the secretory duct. This review provides
      for the latter two systems the highlights of what is known about their general
      physiology and ecophysiology but not their metabolism and their molecular
      biology. It is argued that, given the importance of laticifers and secretory
      ducts to plant defense against insect herbivory, these structures are under
      investigated and deserve more intensive study.

PMID- 18086228
TI  - Structure and function of bordered pits: new discoveries and impacts on whole
      plant hydraulic function.
AB  - Bordered pits are cavities in the lignified cell walls of xylem conduits (vessels
      and tracheids) that are essential components in the water-transport system of
      higher plants. The pit membrane, which lies in the center of each pit, allows
      water to pass between xylem conduits but limits the spread of embolism and
      vascular pathogens in the xylem. Averaged across a wide range of species, pits
      account for > 50% of total xylem hydraulic resistance, indicating that they are
      an important factor in the overall hydraulic efficiency of plants. The structure
      of pits varies dramatically across species, with large differences evident in the
      porosity and thickness of pit membranes. Because greater porosity reduces
      hydraulic resistance but increases vulnerability to embolism, differences in pit
      structure are expected to correlate with trade-offs between efficiency and safety
      of water transport. However, trade-offs in hydraulic function are influenced both
      by pit-level differences in structure (e.g. average porosity of pit membranes)
      and by tissue-level changes in conduit allometry (average length, diameter) and
      the total surface area of pit membranes that connects vessels. In this review we
      address the impact of variation in pit structure on water transport in plants
      from the level of individual pits to the whole plant.

PMID- 18086229
TI  - Can isotopic fractionation during respiration explain the 13C-enriched sporocarps
      of ectomycorrhizal and saprotrophic fungi?
AB  - The mechanism behind the (13)C enrichment of fungi relative to plant materials is
      unclear and constrains the use of stable isotopes in studies of the carbon cycle
      in soils. Here, we examined whether isotopic fractionation during respiration
      contributes to this pattern by comparing delta(13)C signatures of respired CO(2),
      sporocarps and their associated plant materials, from 16 species of
      ectomycorrhizal or saprotrophic fungi collected in a Norway spruce forest. The
      isotopic composition of respired CO(2) and sporocarps was positively correlated.
      The differences in delta(13)C between CO(2) and sporocarps were generally small,
      < +/-1 per thousand in nine out of 16 species, and the average shift for all
      investigated species was 0.04 per thousand. However, when fungal groups were
      analysed separately, three out of six species of ectomycorrhizal basidiomycetes
      respired (13)C-enriched CO(2) (up to 1.6 per thousand), whereas three out of five
      species of polypores respired (13)C-depleted CO(2) (up to 1.7 per thousand; P <
      0.05). The CO(2) and sporocarps were always (13)C-enriched compared with wood,
      litter or roots. Loss of (13)C-depleted CO(2) may have enriched some species in
      (13)C. However, that the CO(2) was consistently (13)C-enriched compared with
      plant materials implies that other processes must be found to explain the
      consistent (13)C-enrichment of fungal biomass compared with plant materials.

PMID- 18086230
TI  - Indirect defence via tritrophic interactions.
AB  - Many plants interact with carnivores as an indirect defence against herbivores.
      The release of volatile organic compounds (VOCs) and the secretion of extrafloral
      nectar (EFN) are induced by insect feeding, a response that is mediated by the
      plant hormone, jasmonic acid. Although VOCs mainly attract predatory mites and
      parasitic wasps, while EFN mainly attracts ants, many more animal-plant
      interactions are influenced by these two traits. Other traits involved in
      defensive tritrophic interactions are cellular food bodies and domatia, which
      serve the nutrition and housing of predators. They are not known to respond to
      herbivory, while food body production can be induced by the presence of the
      mutualists. Interactions among the different defensive traits, and between them
      and other biotic and abiotic factors exist on the genetic, physiological, and
      ecological levels, but so far remain understudied. Indirect defences are
      increasingly being discussed as an environmentally-friendly crop protection
      strategy, but much more knowledge on their fitness effects under certain
      environmental conditions is required before we can understand their ecological
      and evolutionary relevance, and before tritrophic interactions can serve as a
      reliable tool in agronomy.

PMID- 18086231
TI  - Time trends of the prevalence of asthma and allergic disease in Austrian
      children.
AB  - After a substantial increase in the prevalence of atopic disease in Europe,
      recent studies indicate that a plateau has been reached. However, variation
      across countries and age groups exists. We studied the prevalence and time trends
      of asthma and allergic disease among schoolchildren in Austria, a country with
      traditionally low rates of asthma, hay fever, and eczema. As part of the
      International Study of Asthma and Allergies in Childhood (ISAAC), symptoms and
      physician diagnoses of asthma and allergic disease of 13,399 Austrian children
      aged 6-7 yr and 1516 children aged 12-14 yr were surveyed between 1995 and 1997.
      A similar survey was conducted between 2001 and 2003. Among children aged 6-7 yr,
      significant increases were seen in the prevalence of physician-diagnosed asthma
      (+16%; p = 0.013), hay fever (+22%; p < 0.001), and eczema (+37%; p < 0.001)
      between 1995 and 2003. These changes were paralleled by an increase in the
      prevalence of symptoms typical for hay fever (itchy eyes and runny nose), but not
      by an increase in wheeze. Among children aged 12-14 yr, the lifetime prevalence
      of diagnosed asthma increased by 32%, of hay fever by 19%, and of eczema by 28%
      (all, p < 0.001). These changes were paralleled by increases in the prevalence of
      wheezing as documented by both questions before and after a video showing
      wheezing children but not by symptoms typical for hay fever such as itchy eyes
      and runny nose. In conclusion, in Austria, contrary to other European countries,
      the prevalence of asthma and allergic disease increased among schoolchildren.
      Additional studies are needed to continue monitoring the dynamics of the
      prevalence of asthma and allergic disease in Austria and to explore trends in
      their risk factors.

PMID- 18086232
TI  - Higher biomass accumulation by increasing phosphoribosylpyrophosphate synthetase
      activity in Arabidopsis thaliana and Nicotiana tabacum.
AB  - Plants are able to produce all the organic compounds required for development and
      growth. As developmental processes and metabolic pathways use a common resource
      pool, the tight regulation of the distribution of metabolites between growth,
      production of defence compounds and storage products can be assumed. A transgenic
      approach was used to investigate the importance of supplying the key intermediate
      phosphoribosylpyrophosphate (PRPP) for plant growth and biomass accumulation in
      the model plant Arabidopsis thaliana and in Nicotiana tabacum. For this purpose,
      the Ashbya gossypii genes coding for either PRPP synthetase (PRS) or a mutated
      variant of the same gene were over-expressed under the control of a constitutive
      promoter. It was shown that increased PRS activity in A. thaliana or N. tabacum
      leads to a substantial increase in biomass accumulation under different
      standardized growth conditions. Growth enhancement was accompanied by significant
      changes in the amount of sugars and other metabolites. This study provides
      evidence that the supply of PRPP co-limits growth rates, and has obvious
      implications for biotechnological strategies aiming to increase plant biomass as
      an alternative renewable energy source.

PMID- 18086233
TI  - Fruit-specific suppression of the ethylene receptor LeETR4 results in early
      ripening tomato fruit.
AB  - Tomato is an economically important crop and a significant dietary source of
      important phytochemicals, such as carotenoids and flavonoids. Although it has
      been known for many years that the plant hormone ethylene is essential for the
      ripening of climacteric fruits, its role in fruit growth and maturation is much
      less well understood. In this study, data are presented which indicate that fruit
      specific suppression of the ethylene receptor LeETR4 causes early ripening,
      whereas fruit size, yield and flavour-related chemical composition are largely
      unchanged. Early fruit ripening is a highly desirable and valuable trait, and the
      approach demonstrated here should be applicable to any fruit species requiring
      ethylene to ripen. These results demonstrate that ethylene receptors probably act
      as biological clocks regulating the onset of tomato fruit ripening.

PMID- 18086234
TI  - Large-scale phenotyping of transgenic tobacco plants (Nicotiana tabacum) to
      identify essential leaf functions.
AB  - Two of the major challenges in functional genomics are to identify genes that
      play a key role in biological processes, and to elucidate the biological role of
      the large numbers of genes whose function is poorly characterized or still
      completely unknown. In this study, a combination of large-scale expressed
      sequence tag sequencing, high-throughput gene silencing and visual phenotyping
      was used to identify genes in which partial inhibition of expression leads to
      marked phenotypic changes, mostly on leaves. Three normalized tobacco (Nicotiana
      tabacum) cDNA libraries were prepared directly in a binary vector using different
      tissues of tobacco as an RNA source, randomly sequenced and clustered. The
      Agrobacterium-tobacco leaf disc transformation system was used to generate sets
      of antisense or co-suppression transgenic tobacco plants for over 20 000 randomly
      chosen clones, each representing an independent cluster. After transfer to the
      glasshouse, transgenic plants were scored visually after 10-14 days for changes
      in growth, leaf form and chlorosis or necrosis. Putative hits were validated by
      repeating the transformation. This procedure is more stringent than the analysis
      of knockout mutants, because it requires that even a partial decrease in
      expression generates a phenotype. This procedure identified 88 validated
      gene/phenotype relations. These included several previously characterized
      gene/phenotype relationships, demonstrating the validity of the approach. For
      about one-third, a function could be inferred, but a loss-of-function phenotype
      had not been described previously. Strikingly, almost one-half of the validated
      genes were poorly annotated, or had no known function. For 77 of these tobacco
      sequences, a single or small number of potential orthologues were identified in
      Arabidopsis. The genes for which orthologues were identified in Arabidopsis
      included about one-half of the genes whose function was completely unknown.
      Comparison with published gene/phenotype relations for Arabidopsis knockout
      mutants revealed surprisingly little overlap with the present study. Our results
      indicate that partial gene silencing identifies novel gene/phenotype
      relationships, which are distinct from those uncovered by knockout screens. They
      also show that it is possible to perform these analyses in a crop species in
      which full genome sequence information is lacking, and subsequently to transfer
      the information to a reference species in which functional studies can be
      performed more effectively.

PMID- 18086236
TI  - A novel hybrid seed system for plants.
AB  - A two-component hybrid seed system has been developed that is broadly applicable
      and provides for effective generation and maintenance of the male-sterile parent,
      hybrid seed production and full restoration of fertility in the hybrid seed. The
      technology is based on the functional interaction of two loci that are inserted
      in the same position on two homologous chromosomes, and thus are 'linked in
      repulsion', and that jointly code for male sterility and herbicide resistance,
      both traits being expressed in heterozygous plants only. The localization to the
      same locus on a chromosome is achieved by the genetic transformation of plants
      with a construct containing both genetic elements (loci), and subsequent
      derivatization from the primary pro-locus of the two precursor lines using site
      specific deletions. The functional interaction of the two loci is achieved
      through intein-based trans-splicing of two pairs of complementary protein
      fragments that provide for male sterility and herbicide resistance. Unlike the
      hybrid seed systems that are currently in use, the technology relies on the
      genetic modification of just one parent, and is therefore much simpler to develop
      and use. Arabidopsis has been used for the proof of principle presented here, but
      the essential elements of the technology are generic and have been shown to work
      in many crop species.

PMID- 18086237
TI  - Expression of a fungal ferulic acid esterase increases cell wall digestibility of
      tall fescue (Festuca arundinacea).
AB  - In the cell walls of forage grasses, ferulic acid is esterified to arabinoxylans
      and participates with lignin monomers in oxidative coupling pathways to generate
      ferulate-polysaccharide-lignin complexes that cross-link the cell wall. Such
      cross-links hinder cell wall degradation by ruminant microbes, reducing plant
      digestibility. In this study, genetically modified Festuca arundinacea plants
      were produced expressing an Aspergillus niger ferulic acid esterase (FAEA)
      targeted to the vacuole. The rice actin promoter proved to be effective for FAEA
      expression, as did the cauliflower mosaic virus (CaMV) 35S and maize ubiquitin
      promoters. Higher levels of expression were, however, found with inducible heat
      shock and senescence promoters. Following cell death and subsequent incubation,
      vacuole-targeted FAEA resulted in the release of both monomeric and dimeric
      ferulic acids from the cell walls, and this was enhanced several fold by the
      addition of exogenous endo-1,4-beta-xylanase. Most of the FAEA-expressing plants
      showed increased digestibility and reduced levels of cell wall esterified
      phenolics relative to non-transformed plants. It is concluded that targeted FAEA
      expression is an effective strategy for improving wall digestibility in Festuca
      and, potentially, other grass species used for fodder or cellulosic ethanol
      production.

PMID- 18086238
TI  - Gastroenteritis caused by Edwardsiella tarda in a pediatric renal transplant
      recipient.
AB  - Edwardsiella tarda, a member of the family Enterobacteriaceae, is a Gram-negative
      bacillus that is most often pathogenic in aquatic environments. Human infections
      with Edwardsiella are rare, with most occurring in immunocompromised or
      immunosuppressed hosts. Reported infections include meningitis, cholecystitis,
      endocarditis, osteomyelitis, soft tissue infections, bacteremia and septicemia,
      dysentery, and gastroenteritis. This report describes a case of E. tarda
      gastroenteritis in a renal transplant patient receiving immunosuppressive
      therapy. The epidemiology, diagnosis, clinical presentation, and treatment
      options pertaining to E. tarda infections are examined.

PMID- 18086239
TI  - Should the selection of children with hepatocellular carcinoma be based on Milan
      criteria?

PMID- 18086240
TI  - The use of porcine dermal collagen implants in assisting abdominal wall closure
      of pediatric renal transplant recipients with donor size discrepancy.
AB  - Children may have kidneys transplanted from donors larger than themselves.
      Abdominal wall closure may be difficult, with risks of abdominal compartment
      syndrome and graft compromise. Meshes used to facilitate closure may cause dense
      intra-abdominal adhesions, making further surgery or peritoneal dialysis
      difficult. We present five cases in which abdominal wall closure was facilitated
      by porcine dermal collagen implant. Five children (2-15 yr) received transplanted
      kidneys from adult donors of significantly greater weight. In four recipients,
      the kidney was transplanted onto the aorta and vena cava intra-abdominally using
      a midline incision. In the fifth, the kidney was anastomosed onto the iliac
      vessels. The skin overlying the implant was closed normally. Maximum follow-up
      was three yr. In all cases, primary closure was achieved. One child received a
      second intra-abdominal transplant as an emergency, which later failed. The other
      kidneys are functioning well. One recipient developed a small incisional hernia
      three yr post-transplant. Another developed a skin dehiscence over the implant 23
      days post-operatively. The implant was removed and skin closed. The other two
      recipients recovered well. Porcine dermal collagen implant is a helpful adjunct
      to abdominal wall closure following organ transplantation in children with donor
      size discrepancy.

PMID- 18086241
TI  - The phototoxicity of aged human retinal melanosomes.
AB  - The purpose of this study was to determine whether an age-related increase in
      photoreactivity of human retinal melanosomes (MS) can cause phototoxicity to
      retinal pigment epithelium (RPE) cells. MS were isolated post mortem from young
      (20-30 years, young human melanosomes [YHMs]) and old (60-90 years, old human
      melanosomes [OHMs]) human eyes and from young bovine eyes (bovine melanosomes
      [BMs]). Confluent cultured ARPE-19 cells were fed equivalent numbers of OHMs or
      BMs and accumulated similar amounts of melanin as determined by electron
      paramagnetic resonance assay. Cells with and without MS were either maintained in
      the dark or exposed to blue light for up to 96 h and assessed for alterations in
      cell morphology, cell viability and lysosomal integrity. Incubation of cells in
      dark in the presence of internalized MS or irradiation of cells with blue light
      in the absence or presence of BMs did not significantly affect cell viability.
      However, exposures to blue light in the presence of OHMs resulted in abnormal
      cell morphology, up to approximately 75% decrease in mitochondrial activity, loss
      of lysosomal pH and cell death. OHMs contained significantly less melanin than
      YHMs, supporting the hypothesis that melanin undergoes degradation during RPE
      aging. Our results demonstrate that aged MS can be phototoxic to human RPE cells
      and support a contributing role of MS in RPE aging and in the pathogenesis of age
      related macular degeneration.

PMID- 18086242
TI  - Topical treatment with OGG1 enzyme affects UVB-induced skin carcinogenesis.
AB  - Nonmelanoma skin cancer resulting from UVB exposure is a large and growing
      problem in the United States. Production of reactive oxygen species (ROS) during
      the UVB-induced inflammatory response results in the formation of oxidative DNA
      adducts such as 8-hydroxy-2-deoxyguanine (8-oxo-dG), which have been shown to
      contribute to the development of this cancer. The 8-oxoguanine DNA glycosylase
      (OGG1) enzyme repairs 8-oxo-dG adducts, suggesting that enhancing its activity in
      the skin might increase 8-oxo-dG repair thus preventing skin cancer development.
      We therefore used the SKH-1 murine model to examine the effect of topically
      applied OGG1 on UVB-induced skin cancer development. Mice were exposed three
      times weekly to UVB followed immediately by topical treatment with a formulation
      of liposome-encapsulated OGG1 enzyme for 25 weeks. While this treatment did not
      affect UVB-induced tumor multiplicity, it did reduce tumor size and dramatically
      reduced tumor progression, as indicated by tumor grade. These results suggest
      that oxidative DNA damage contributes to the progression of UVB-induced skin
      tumors and that a topical formulation containing OGG1, perhaps in conjunction
      with other DNA repair enzymes such as T4 endonuclease V, could be used in
      populations at high risk for skin cancer development.

PMID- 18086243
TI  - The use of commercially available personal UV-meters does cause less safe tanning
      habits: a randomized-controlled trial.
AB  - UV Index information is currently recommended as a vehicle to raise public
      awareness about the risk of sun-exposure. It remains unknown to what extent this
      information can change personal sun-protective behavior. The aim of the study was
      to analyze the effects of UV-Index (UV-I) information provided by low cost,
      commercially available UV-I sensors on major indicators of sun-tanning behavior.
      A randomized-controlled trial was carried out on 94 healthy volunteers aged 21-23
      years. After the exclusion of subjects with photosensitive disorders (n=3), 91
      subjects were randomized in two arms after stratification based on phototype and
      sex. Both arms received a diary to be filled every day with a log of intentional
      sun-exposure during summer. Subjects in the intervention group also received a
      commercially available UV-I sensor. The UV-I sensors were switched on and the UV
      value was recorded in 77% of days with sun-exposure. During days of sun-exposure,
      subjects randomized to the intervention group had longer average time of sun
      exposure (227.7 vs 208.7 min per day, P=0.003), also between noon and 4 pm
      (P<0.001), and less frequently adopted sun protective measures than controls (hat
      [6.4%vs 10.2%, P=0.007], sunglasses [23.9%vs 30.8%, P=0.003], sunscreen [41.4%vs
      47.2%, P=0.02]) and they experienced more frequent sunburns (27.8%vs 21.5%,
      P=0.004). The odd ratio of sunburns was 1.60 for subjects in the intervention
      group compared with controls (after adjustment for sex, sunscreen use and skin
      type). The mean UV-I value recorded by volunteers was lower (5.6 [SD+/-0.9]) than
      that (7.3 [SD+/-0.46]) recorded by a professional instrument in the same period
      at the same latitude. Poststudy laboratory tests showed that the sensor was able
      to detect only about 60% of the solar diffuse radiation. The use of UV-I sensors
      changed the sun protective behavior of sunbathers in the direction of less use of
      sun protective measures. One possible explanation is that the low cost UV-meters
      may have functioned incorrectly and under-reported UV exposure. This may have led
      to an underestimation of UV-I values, erroneously reassuring subjects and causing
      a less protective sunbathing behavior. Another hypothesis relies on a cognitive
      pitfall in the subjects' dealing with intermediate UV-I values, as they may have
      been discouraged in the use of sunscreen as they did not feel that they had yet
      been exposed to very harmful UV radiation.

PMID- 18086244
TI  - Naringenin protects HaCaT human keratinocytes against UVB-induced apoptosis and
      enhances the removal of cyclobutane pyrimidine dimers from the genome.
AB  - Many naturally occurring agents are believed to protect against UV-induced skin
      damage. In this study, we have investigated the effects of naringenin (NG), a
      naturally occurring citrus flavonone, on the removal of UVB-induced cyclobutane
      pyrimidine dimers (CPD) from the genome and apoptosis in immortalized p53-mutant
      human keratinocyte HaCaT cells. The colony-forming assay shows that treatment
      with NG significantly increases long-term cell survival after UVB irradiation. NG
      treatment also protects the cells from UVB-induced apoptosis, as indicated by the
      absence of the 180 base pair DNA ladders and the appearance of sub-G1 peak using
      agarose gel electrophoresis and flow cytometric analysis, respectively. The UVB
      induced poly (ADP-ribose) polymerase-1 (PARP-1) cleavage, caspase activation and
      Bax/Bcl2 ratio were modulated following NG treatment, indicating an antiapoptotic
      effect of NG in UVB-damaged cells that occurs at least in part via caspase
      cascade pathway. Moreover, treatment of UVB-irradiated HaCaT cells with NG
      enhances the removal of CPD from the genome, as observed by both direct
      quantitation of CPD in genomic DNA and immuno-localization of the damage within
      the nuclei. The study provides a molecular basis for the action of NG as a
      promising natural flavonoid in preventing skin aging and carcinogenesis.

PMID- 18086246
TI  - Protection from sunburn with beta-Carotene--a meta-analysis.
AB  - Nutritional protection against skin damage from sunlight is increasingly
      advocated to the general public, but its effectiveness is controversial. In this
      meta-analysis, we have systematically reviewed the existing literature on human
      supplementation studies on dietary protection against sunburn by beta-carotene. A
      review of literature until June 2007 was performed in PubMed, ISI Web of Science
      and EBM Cochrane library and identified a total of seven studies which evaluated
      the effectiveness of beta-carotene in protection against sunburn. Data were
      abstracted from these studies by means of a standardized data collection
      protocol. The subsequent meta-analysis showed that (1) beta-carotene
      supplementation protects against sunburn and (2) the study duration had a
      significant influence on the effected size. Regression plot analysis revealed
      that protection required a minimum of 10 weeks of supplementation with a mean
      increase of the protective effect of 0.5 standard deviations with every
      additional month of supplementation. Thus, dietary supplementation of humans with
      beta-carotene provides protection against sunburn in a time-dependent manner.

PMID- 18086247
TI  - Molecular recognition in partially folded states of a transporter protein:
      temperature-dependent specificity of bovine serum albumin.
AB  - The specificity of molecular recognition of a transporter protein bovine serum
      albumin (BSA) in its different partially folded states has been studied. In order
      to avoid complications due to chemical denaturation, we have prepared thermally
      induced partially folded states of the protein. The partially folded states have
      been structurally characterized by circular dichroism and differential thermal
      analysis techniques. The change in the globular structure of the protein as a
      consequence of thermal unfolding has also been characterized by dynamic light
      scattering. Steady state, picosecond-resolved fluorescence and polarization gated
      spectroscopies on the ligands (DCM, LDS 750) in the protein reveal the dynamics
      of the binding sites and the specificity of ligand binding of BSA. Picosecond
      resolved Forster resonance energy transfer studies on the donor DCM and acceptor
      LDS 750 confirm that the specificity of ligand binding in the binding site is
      maintained up to 70 degrees C. At 75 degrees C, the protein loses its specificity
      of recognition at the aforesaid site.

PMID- 18086248
TI  - The extent of DNA deformation in DNA photolyase-substrate complexes: a solution
      state fluorescence study.
AB  - Cyclobutylpyrimidine dimers (CPDs) are the major UV photoproduct formed in DNA
      containing adjacent pyrimidines. These lesions can be repaired by DNA photolyase,
      a flavoprotein that utilizes blue light in a direct reversal of the cyclobutane
      ring. Previous studies have shown that the CPD is base flipped into the protein,
      with concomitant disruption of the substrate around the CPD. In this study, we
      use a fluorescent cytidine analog, pyrrolo-dC (PC), to probe how far base
      flipping propagates along the duplex. From these measurements, the degree of base
      destacking in the two bases flanking the adenines opposing the CPD appears to be
      minimal, which was consistent with the protein:substrate crystal structure.
      Fluorescence-detected melting temperatures for duplexes with and without a CPD
      were obtained, suggesting that a 5'-pyrimidine-PC-purine-3' motif is more stable
      than the 5'-purine-PC-pyrimidine-3' motif. This stability trend was reflected in
      the fluorescence intensities of ss-PC oligos but not for duplexes. The melting
      point depression due to the PC probe was found to be comparable to other popular
      fluorescent base analogs.

PMID- 18086249
TI  - Therapeutic idiosyncrasy.

PMID- 18086245
TI  - Understanding signaling cascades in melanoma.
AB  - Understanding regulatory pathways involved in melanoma development and
      progression has advanced significantly in recent years. It is now appreciated
      that melanoma is the result of complex changes in multiple signaling pathways
      that affect growth control, metabolism, motility and the ability to escape cell
      death programs. Here we review the major signaling pathways currently known to be
      deregulated in melanoma with an implication to its development and progression.
      Among these pathways are Ras, B-Raf, MEK, PTEN, phosphatidylinositol-3 kinase
      (PI3Ks) and Akt which are constitutively activated in a significant number of
      melanoma tumors, in most cases due to genomic change. Other pathways discussed in
      this review include the [Janus kinase/signal transducer and activator of
      transcription (JAK/STAT), transforming growth factor-beta pathways which are also
      activated in melanoma, although the underlying mechanism is not yet clear. As a
      paradigm for remodeled signaling pathways, melanoma also offers a unique
      opportunity for targeted drug development.

PMID- 18086250
TI  - Invest now to save later: the need for a national quality improvement initiative
      to reduce the costs of liver transplantation in children.

PMID- 18086251
TI  - Screening for rejection in symptomatic pediatric heart transplant recipients: the
      sensitivity of BNP.
AB  - As the pediatric OHT population expands, there is increasing demand for
      convenient, yet sensitive screening techniques to identify children with acute
      rejection when they present to acute care facilities. In children, symptoms of
      acute rejection or other causes of graft dysfunction are often non-specific and
      can mimic other childhood illnesses. The aim of this study was to assess the
      utility of BNP as a biomarker to assist providers in clinical decision-making
      when evaluating symptomatic pediatric heart transplant patients. One hundred
      twenty-two urgent care and emergency room visits from 53 symptomatic pediatric
      OHT patients were retrospectively reviewed to evaluate the relationship between
      BNP levels, symptoms, and clinical diagnosis at these visits. An ROC curve was
      generated to determine the accuracy of BNP as a screening tool for acute
      rejection in this patient population. In this group of patients, a BNP value of
      >700 pg/mL was 100% sensitive and 92% specific for detecting allograft acute
      rejection (NPV of 100%). We concluded that BNP is a highly sensitive screening
      test for acute rejection in symptomatic pediatric heart transplant patients.

PMID- 18086252
TI  - Quantification and viability assessment of isolated bovine primordial and primary
      ovarian follicles retrieved through a standardized biopsy pick-up procedure.
AB  - The feasibility of repeated collection and enzymatic isolation of large numbers
      of viable primordial and primary follicles from living donor cows were tested.
      Ovarian cortical biopsies were collected transvaginally by the Biopsy Pick-Up
      (BPU) device, a modification of an Ovum Pick-Up instrument. Follicles were
      enzymatically isolated from the retrieved cortical tissue samples, and follicle
      viability was determined by a live/dead fluorescent assay. Six cows were
      subjected to BPU once per week during 4 consecutive weeks, and in each BPU
      session 4 cortical tissue samples were collected per ovary. Over the 4-week trial
      period, a total of 1443 primordial and primary follicles were collected, 1358
      (94%) of which were primordial and 85 (6%) were primary follicles. In each BPU
      session, an average 60.1 +/- 10.7 (mean +/- SEM) primordial and primary follicles
      were isolated per cow. The number of follicles varied considerably throughout the
      trial period and between cows. Statistical analysis of the data, however, did not
      support the presence of any distinct trends in the follicle yields over time or
      between cows. A total of 111 enzymatically isolated follicles were analyzed for
      viability with fluorescent probes. The vast majority of isolated follicles
      (92.8%) were totally viable. We conclude that the standardized BPU procedure
      generates sufficiently large numbers of vital primordial and primary follicles,
      thus validating BPU as a new tool for research into early bovine follicular
      development.

PMID- 18086253
TI  - Effect of a gonadotropin-releasing hormone vaccine (Improvac) on steroid
      hormones, boar taint compounds and performance in entire male pigs.
AB  - The objective of this study, comprising two trials, was to evaluate the effect of
      a gonadotropin-releasing hormone (GnRH [corrected] vaccine Improvac; Pfizer Ltd)
      in a sample of the Swedish pig population. The pigs (n = 120) were assigned to
      three groups: control (entire male pigs), surgical castration and immunization
      against GnRH. Surgically castrated pigs did not express detectable levels of
      either testosterone or estrone sulphate (E1S) in plasma, or androstenone in fat
      and had lower skatole and indole levels in fat than entire male pigs.
      Immunization significantly reduced testes weight and bulbourethral gland length,
      plasma levels of the testicular hormones testosterone and E1S, and fat levels of
      androstenone, skatole and indole. Skatole levels in plasma were significantly
      lower than in entire male pigs in the second trial, but not in the first due to
      overall low skatole levels. All immunized pigs and surgically castrated pigs
      expressed skatole concentrations in fat below the level of 0.2 microg/g, above
      which meat is regarded as tainted. In contrast, eight entire male pigs exceeded
      this level. Indole levels in plasma from immunized pigs were lower than those
      from entire male pigs. Surgical castration caused lower daily weight gain in the
      suckling period compared with piglets raised intact, whereas in the post-weaning
      period no difference was observed. Immunization resulted in higher feed intake
      and daily weight gain after the second injection. The estimated lean meat content
      was improved in comparison with the castrated pigs, but was lower than for entire
      male pigs. Dressing percentage was lower in immunized pigs than in surgically
      castrated and entire male pigs. The frequency of skin damage did not differ
      between immunized and entire male pigs or between immunized and surgically
      castrated pigs.

PMID- 18086254
TI  - Field investigation of perinatal mortality in friesian cattle associated with
      myocardial degeneration and necrosis.
AB  - Perinatal mortality and stillbirths were investigated in an extensively managed
      herd of Friesian cows and heifers calving over a 2-year period: 504 cows were
      calved and 215 heifers. Cows were bred to Friesian and Jersey bulls using natural
      service. The perinatal fetal mortality rate was 7.5% for cows and 30% for
      heifers. An experienced stockman managed these calvings and veterinary assistance
      was required only on nine occasions. All stillborn fetuses were examined post
      mortem by the Veterinary Laboratories Agency, Carmarthen and no infectious agent
      was identified on any occasion. Thyroid hyperplasia was found in two fetuses. In
      blood samples taken from 10 late pregnant heifers, mean glutathione peroxidase
      values were 7.9 +/- 1.7 IU/ml Packed Cell Volume (PCV). Tissues from eight
      fetuses were submitted to the University of Liverpool for histopathological
      examination; all presented lesions consistent with myocardial degeneration and
      necrosis of the left ventricle. Following treatment of 205 late pregnant heifers
      with sodium selenite and vitamin E, the overall perinatal mortality rate in these
      cattle fell to below 11%.

PMID- 18086255
TI  - Calves born after direct transfer of vitrified bovine in vitro-produced
      blastocysts derived from vitrified immature oocytes.
AB  - Vitrification has been the method of choice for the cryopreservation of bovine
      oocytes, as rapid cooling decreases chilling sensitivity. The aim of this study
      was to determine the in vitro and in vivo survival and the viability of immature
      oocytes vitrified using super-cooled liquid nitrogen. Immature oocytes were
      randomly allocated to three groups: (i) non-vitrified control group, (ii)
      vitrified in normal (-196 degrees C) liquid nitrogen (LN(2)) and (iii) vitrified
      in super-cooled LN(2) (< or =-200 degrees C). Open-pulled glass micropipettes
      were used as vitrification containers. Immature oocytes were in vitro-matured,
      fertilized and cultured to the blastocyst stage. In vitro viability was assessed
      by cleavage and blastocyst rates on days 2 and 7 of culture respectively.
      Vitrified blastocysts derived from the immature vitrified oocytes were directly
      transferred to synchronous recipients. The in vitro embryo development of
      vitrified immature oocytes was not influenced by the LN(2) state. After direct
      transfer (one embryo per recipient) of 16 embryos obtained from immature
      vitrified oocytes (eight from each vitrified group), two healthy calves were born
      in each group. These results indicated that vitrification of immature bovine
      oocytes using glass micropipettes under normal or super-cooled LN(2), resulted in
      viable blastocysts and live calves following in vitro embryo production.

PMID- 18086256
TI  - Fludarabine based reduced intensity conditioning regimens in children undergoing
      allogeneic stem cell transplantation for severe aplastic anemia.
AB  - Fourteen children with a median age of 9.8 yr with SAA (10 males, four females)
      underwent related HLA identical allogeneic stem cell transplantation using Flu,
      Cy +/- ATG between 2004 and 2006. GVHD prophylaxis consisted of cyclosporine +/-
      mini methotrexate. Graft source included PBSCs (seven) or BM (seven). One patient
      expired <7 days post-transplant, while 12 (85.7%) patients engrafted with median
      neutrophil and platelet engraftment times of 13.8 and 14.5 days each. One patient
      had primary graft failure and expired on Day +27. Acute GVHD was seen in 25% of
      evaluable patients while limited chronic GVHD was seen in 33%. At a mean follow
      up of 18 months, 12 patients (85.7%) are alive and well. Compared with a
      historical cohort of 12 children transplanted using Cy/ATG, there was faster
      engraftment (13.8 vs. 16.4 days; p = 0.002) with lower rejection rates (7.1 vs.
      36.3%; p = 0.133) and improved event free (85.7 vs. 54.5%; p = 0.177) and overall
      survival (85.7 vs. 63.6%; p = 0.350). Flu with Cy +/- ATG reduces rejection and
      improves overall and event free survival in children with aplastic anemia.

PMID- 18086257
TI  - An unexpected finding on chest roentgenogram following hemodialysis catheter
      placement.

PMID- 18086258
TI  - Palliative care: misconceptions that limit access for patients with chronic renal
      disease.
AB  - There is an urgent need to incorporate palliative care into the treatment of
      patients with end-stage renal disease (ESRD). These patients have a shortened
      lifespan and face end-of-life decisions as renal function declines and renal
      replacement therapy becomes necessary. They also experience a high symptom burden
      as a result of the illness as well as its treatment. Why, then, do patients with
      ESRD rarely receive expert palliative care services that have been shown to
      enhance the quality of life of patients with other life-limiting illnesses? The
      lack of access to palliative care can be attributed, in part, to misconceptions
      about its philosophy and goals. It is hoped that clarification of these
      misconceptions will facilitate integration of palliative care into routine
      nephrology practice.

PMID- 18086259
TI  - How dialysis is paid for: what the dialysis medical director should know, and
      why.
AB  - While Medicare funds neither 100% of the patients, nor 100% of the costs incurred
      by dialysis patients, Medicare's policies dominate reimbursement. The medical
      director is well advised to understand these mechanisms and the processes leading
      to change. Medicare pays for dialysis according to laws and rules enacted by
      Congress. Congress is re-evaluating the funding of the end-stage renal disease
      program. The rules are changing. They are changing in a way designed to encourage
      better outcomes, and increased provider accountability. The new terms of art are
      "budget neutrality,""quality incentive payments," and "bundled composite rate."
      Providers will need to make choices that may impact the quality of care and the
      experience of the patient. It is up to the medical director to ensure that these
      choices result in benefit to their patients.

PMID- 18086260
TI  - TNF-alpha induction by Pseudomonas aeruginosa lipopolysaccharide or slime
      glycolipoprotein in human monocytes is regulated at the level of Mitogen
      activated Protein Kinase activity: a distinct role of Toll-like receptor 2 and 4.
AB  - TNF-alpha production has a central role in the development and progression of
      Pseudomonas aeruginosa septic shock. We have previously shown that P. aeruginosa
      slime-glycolipoprotein (slime-GLP) is the most potent stimulant compared to P.
      aeruginosa lipopolysaccharide (LPS), for TNF-alpha production and NF-kB
      activation in human monocytes. Herein, we show that secretion of TNF-alpha by
      fresh human monocytes, induced by P. aeruginosa slime-GLP, LPS or viable
      bacteria, was paralleled by phosphorylation and/or activation of Mitogen
      activated Protein Kinases (MAPKs) ERK1/2, p38 as well as c-Jun NH(2)-terminal
      kinase. TNF-alpha levels were significantly reduced by ERK1/2 inhibitor
      (PD98059), or p38 inhibitor (SB203580). Combination of both inhibitors almost
      abolished TNF-alpha induction. Pseudomonas aeruginosa slime-GLP differed from the
      P. aeruginosa-LPS only regarding the strength of p38 and ERK1/2 activation, with
      slime-GLP leading to a stronger activation of p38 and ERK1/2. Involvement of TLR2
      and TLR4 for phosphorylation of p38 and ERK1/2 was shown using specific blocking
      anti-TLR2 and anti-TLR4 antibodies. Activation of both p38 and ERK1/2 induced by
      P. aeruginosa slime-GLP was dramatically reduced in the presence of anti-TLR2 and
      to a lesser degree in the presence of anti-TLR4, whereas the P. aeruginosa-LPS
      induced stimulation was inhibited only in the presence of anti-TLR4. Our data
      show that P. aeruginosa viable bacteria, through slime-GLP, stimulate specific
      members of the MAPKs more efficiently than the P. aeruginosa-LPS, involving
      mainly TLR2.

PMID- 18086261
TI  - The effect of specific MHC class I and class II combinations on resistance to
      furunculosis in Atlantic salmon (Salmo salar).
AB  - The aim was to evaluate the performance of selected individual major
      histocompatibility complex (MHC) class I and class II alleles and combinations of
      these on disease resistance against furunculosis. The material, consisting of
      2,145 Atlantic salmon (Salmo salar) from seven families, contained four MHC class
      I (UBA) alleles and two MHC class II alpha (DAA) alleles. The included alleles
      were previously shown to influence resistance towards furunculosis. The fish were
      challenged with the bacterium Aeromonas salmonicidae, causing furunculosis. The
      total mortality in the material was 84.0%, and both dead and surviving fish were
      genotyped for UBA and DAA. For MHC class II fish with DAA*0301 were more
      resistant than fish with DAA*0201, which were significantly more susceptible (P <
      0.05). For MHC class I, the ranking of performance of the alleles differed from
      previous results, and fish with allele UBA*0601 were found to be most resistant
      while fish with UBA*0501, UBA*0201 and UBA*0301 were more susceptible. The
      analysis of combined MHC class I and class II genotype detected that fish with
      genotypes UBA*0501/*0501;DAA*0301/*0301, UBA*0601/*0601;DAA*0301/*0301 and
      UBA*0601/*0601;DAA*0201/*0201 were most resistant (P < 0.05), while the genotypes
      associated with increased susceptibility were UBA*0501/*0501; DAA*0201/*0301 and
      UBA*0501/*0501;DAA*0201/*0201 (P < 0.05). In addition, Cox regression analysis
      show that both family and MHC alleles contributed significantly to survival.
      Thus, in addition to reproducing the effect on resistance and susceptibility of
      many MHC class I and class II alleles individually, we also detected an effect of
      certain MHC class I and class II combinations suggestive of cross-talk between
      the class I and class II pathways.

PMID- 18086262
TI  - Naturally acquired immunity and reduced susceptibility to falciparum malaria in
      two subpopulations of endemic eastern India.
AB  - This study was aimed to assess the prevalence of naturally acquired humoral
      immune responses and their association with reduced susceptibility to malaria in
      children and adults with differential clinical conditions from an Indian zone
      where malaria is endemic. The study was undertaken in an eastern province of
      India (Keonjhar, Orissa) in a group of 341 children (both younger and older) and
      98 adults living in two different areas, Town area and Forest area. They were
      studied for their parasitological and immunological profiles. Sera from different
      age-matched groups were screened by ELISA to measure IgG reactivities for
      characterizing humoral immune responses to the B-cell epitopes of Plasmodium
      falciparum MSP1, AMA1, RAP1 and EBA175 peptides and P. falciparum-infected
      erythrocyte lysate. In Town area, overall P. falciparum cases were 5.5%, whereas
      those in Forest area were 26.7%. We observed an age-wise increasing trend of
      immunity in these two populations. It was also noticed that the frequency of
      responders to stage-specific antigens was higher in individuals from the Town
      area where the frequency of malaria was lower. The naturally acquired humoral
      immune responses to different stage-specific antigens of P. falciparum reflect
      the reduced risk of malaria in the study groups. The higher frequency of
      seroresponders showed correlation with lower risk of developing malaria.

PMID- 18086263
TI  - Perceived barriers to physical activity across Norwegian adult age groups, gender
      and stages of change.
AB  - This study investigated differences in the type of and number of perceived
      barriers to engagement in physical activity experienced by adult women and men in
      the same geographical area, the relationship between the experienced barriers and
      stages of change in relation to exercise behavior, and identified barriers
      related to reported engagement in leisure-time physical activity. Data were
      obtained from a population study by the National Institute of Public Health in
      two counties during 2000-2001. The sample consisted of 2709 females and 2212 men
      in the age groups 75, 60, 45, 40 and 30 years. Questionnaires measured barriers
      to engagement in physical activity, engagement in physical activity and readiness
      for engaging in physical activity (stages of change). Multivariate analyses of
      variance demonstrated significant age and gender differences in the perceptions
      of barriers at the various stages of change. The logistic regressions [estimated
      odds ratios (OR)] demonstrated that low scores for affective/cognitive and
      practical barriers were significantly associated with higher OR for engagement in
      physical activity for women, and low-priority barriers and lower age were
      associated with higher OR for being physically active for men. The information
      from this study should be valuable for designing and tailoring both motivational
      strategies and interventions to fit targeted groups.

PMID- 18086264
TI  - DRB1*1613N: a novel DRB1 allele with a premature termination codon.
AB  - DRB1 null alleles are extremely rare and always sporadic, suggesting their
      biological selective disadvantage.

PMID- 18086265
TI  - Evaluating the role of HLA-DQ polymorphisms on immune response to bacterial
      superantigens using transgenic mice.
AB  - Bacterial superantigens bind directly to human leukocyte antigen (HLA) class II
      molecules and vigorously activate T cells expressing certain T-cell receptor
      variable region families. As interaction with HLA class II molecules is the
      primary step in this process, polymorphic variations in HLA class II can
      determine the extent of superantigen binding to HLA class II molecules, govern
      the magnitude of immune activation induced by given superantigens and determine
      the outcome of superantigen-mediated diseases. As direct assessment of the
      influence of HLA class II polymorphism in humans is impossible because of
      expression of more than one HLA class II alleles in a given individual and
      toxicity of superantigens, transgenic mice expressing HLA-DQ6 (HLA-DQA1*0103 and
      HLA-DQB1*0601) and HLA-DQ8 (HLA-DQA1*0301 and HLA-DQB1*0302) were used to achieve
      this goal. HLA-DQ6 and HLA-DQ8 elicited comparable in vitro and in vivo immune
      response to staphylococcal enterotoxins (SE) A, SEB, SEH and SEK, toxic shock
      syndrome toxin-1, streptococcal pyrogenic exotoxin (SPE) A and SPEC and
      streptococcal mitogenic exotoxin Z (SMEZ). However, each superantigen had a
      unique T-cell receptor activation profile. In vivo challenge with Streptococcus
      pyogenes, H305, capable of elaborating SPEA and SMEZ, yielded a similar clinical
      outcome in HLA-DQ6 and HLA-DQ8 transgenic mice. In conclusion, HLA-DQ6 and HLA
      DQ8 elicited comparable response to certain bacterial superantigens. Our report
      highlights the advantages of HLA class II transgenic mice in such studies.

PMID- 18086266
TI  - IL-12Bpro and GSTP1 polymorphisms in association with silicosis.
AB  - To assess the role of IL-12Bpro and GSTP1 polymorphisms on induced interleukin
      (IL)-12p40 production in respect to silicosis development, we examined their
      distribution in 63 silicosis patients and 165 healthy donors. Decreased
      frequencies of IL-12Bpro-2 allele (42% vs 62.5%, P = 0.0042) and genotype 22 (19%
      vs 40%, P = 0.02) in patients compared with exposed healthy donors suggested
      their protective role in silicosis susceptibility. The GSTP1 A/G polymorphism was
      also associated with silicosis susceptibility. The allele G and genotype GG were
      overrepresented among patients than among healthy men (36% vs 23%, P = 0.013; 14%
      vs 2%, P(c) = 0.012). Also, patients' peripheral blood mononuclear cell (PBMC)
      produced higher IL-12p40 than healthy donors' depending on both IL-12Bpro and
      GSTP1 polymorphisms. In conclusion, homozygosity of high producer IL-12p40
      genotype IL-12Bpro-11 and GSTP1-GG had the highest genetic risk of silicosis
      development in Bulgarian miners.

PMID- 18086267
TI  - HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in the Kinh population in
      Vietnam.
AB  - Allele and haplotype frequencies of the human leukocyte antigens (HLA) were
      studied in the Kinh Vietnamese population. We analyzed 170 unrelated healthy
      individuals. DNA-based HLA typing was performed using a microsphere-based array
      genotyping platform with sequence-specific oligonucleotide probes to distinguish
      HLA-A, -B, -C, -DRB1 and -DQB1 alleles. A total of 21 HLA-A, 37 HLA-B, 18 HLA-C,
      25 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. HLA-A*1101, A*2402, A*3303,
      B*1502, B*4601, Cw*0102, Cw*0702, Cw*0801, DRB1*1202, DQB1*0301, DQB1*0303, and
      DQB1*0501 were found with frequencies higher than 10%. Two representative
      haplotypes bearing two to five HLA loci were A*1101-B*1502 and A*3303-B*5801 for
      HLA-A-B; Cw*0801-B*1502 and Cw*0102-B*4601 for HLA-C-B; B*1502-DRB1*1202 and
      B*4601-DRB1*0901 for HLA-B-DRB1; DRB1*1202-DQB1*0301 and DRB1*0901-DQB1*0303 for
      HLA-DRB1-DQB1; A*1101-Cw*0801-B*1502 and A*3303-Cw*0302-B*5801 for HLA-A-C-B;
      A*1101-B*1502-DRB1*1202 and A*2901-B*0705-DRB1*1001 for HLA-A-B-DRB1, A*1101
      Cw*0801-B*1502-DRB1*1202-DQB1*0301 and A*2901-Cw*1505-B*0705-DRB1*1001-DQB1*0501
      for HLA-A-C-B-DRB1-DQB1. Allele distribution and haplotype analysis demonstrated
      that the Vietnamese population shares HLA patterns with southern Chinese, Thai,
      Javanese and Micronesians, while it also retains unique characteristics.

PMID- 18086268
TI  - Identification of the very uncommon allele HLA-Cw*0716 in a Caucasian renal
      transplant recipient: extension of the exon 4 sequence.
AB  - This report describes the unknown exon 4 sequence of the rare human leukocyte
      antigen-Cw*0716 allele, identified in a Caucasian renal transplant recipient from
      Italy. This sequence is identical to the Cw*070101 allele, and this result
      allowed us to confirm the hypothesis of the generation of Cw*0716 allele by an
      interallelic recombination event between Cw*0701/0706/0718 and Cw*020202 allele.

PMID- 18086269
TI  - Constitutive nitric oxide synthase gene polymorphisms and house dust mite
      respiratory allergy in an Algerian patient group.
AB  - Genetic polymorphisms in neuronal nitric oxide synthase (NOS1) and calmodulin
      dependent endothelial NOS (NOS3) genes are known to influence the course of
      allergic respiratory disorders. We investigated the role of NOS1 -84 G-->A and
      NOS3 -786 T-->C, 894 G-->T and 27 base pair (bp) repeat polymorphisms in 125
      patients suffering from asthma and/or rhinitis and monosensitized against
      Dermatophagoides pteronyssinus (Dpter) and 111 controls from Algeria. We found a
      higher frequency of the -786 C NOS3 allele in patients than in controls
      [corrected P value (Pc) = 0.04], especially in female cases (Pc = 0.02) and that
      the 'ab' genotype of the 27-bp polymorphism was significantly associated with
      specific immunoglobulin E production against Dpter (P = 0.006). This study brings
      further support for the participation of NOS3 gene polymorphism in the
      pathogenesis of respiratory allergic disorders.

PMID- 18086270
TI  - An update on prognosis in breast cancer patients with extensive axillary disease.
AB  - Lymph node (LN) status is the most important factor in predicting survival in
      breast cancer. Historically, patients with 10 or more positive LN have been
      thought to have a particularly poor prognosis, which has in the past been used to
      alter therapeutic recommendations. Studies conducted both prior to and after the
      use of anthracycline-based chemotherapy demonstrate poor survival. We
      hypothesized that the current survival rate is considerably higher. All patients
      with breast cancer treated at our institution between July 1991 and December 2005
      with at least 10 positive axillary LN were identified. A multivariate Cox
      proportional hazards model was performed using age, number of positive nodes, and
      primary tumor characteristics. Of 55 patients identified, two were excluded for
      incomplete follow-up information. The median patient age was 53; median follow-up
      was 5-years. The overall 5-year survival rate was 71.9%. On univariate analysis
      estrogen receptor (ER) status (p = 0.0001), progesterone receptor status (p =
      0.004), use of adjuvant chemotherapy (p = 0.01), T-stage (p = 0.03), and adjuvant
      hormonal therapy (p = 0.002) were statistically significant for survival. In the
      multivariate analysis, only ER status and the use of adjuvant chemotherapy
      remained significant for survival. ER negativity conferred a hazard ratio of 12.6
      (95% confidence interval: 3.7-43.2) and the use of adjuvant chemotherapy had a
      hazard ratio of 0.14 (95% confidence interval: 0.04-0.46). In our study, patients
      with at least 10 positive axillary LN had a 5-year survival of 71.9% which may be
      due to the improvements in local and systemic therapy.

PMID- 18086271
TI  - Hereditary breast cancer: part II. Management of hereditary breast cancer:
      implications of molecular genetics and pathology.
AB  - Management of patients at high risk for hereditary breast cancer (HBC) must
      critically assess its phenotypic and genotypic heterogeneity, particularly
      evidenced by the varying spectra of cancer sites that are integral to the
      respective HBC syndromes. Targeted management must consider their biology,
      pathology, and molecular genetics, all in concert with their respective
      carcinogenic pathways, as they may differ significantly from one breast cancer
      syndrome to the next. A striking example of management differences pertains to
      BRCA1 and BRCA2 mutation-positive breast cancers wherein those with BRCA1
      mutations are frequently estrogen receptor (ER)-negative in contrast to BRCA2
      mutations which are more frequently ER-positive; therein, significant differences
      exist with respect to anti-estrogen therapy which will be more amenable to BRCA2
      versus BRCA1 mutation carriers manifesting breast cancer. In turn, tumors that
      are negative for ER, PR, and Her2-neu, often referred to as "triple negative"
      tumors, may also harbor a unique basal-like gene expression profile and are
      characterized by poor prognosis wherein endocrine and/or Her2-neu-targeted
      therapies are not effective treatment options. A further confounder pertains to
      the lifetime risk for ovarian cancer, which differs strikingly between BRCA1
      mutation carriers, who show a 40-60% lifetime risk, and their BRCA2 counterparts,
      who carry a lifetime risk of approximately 12-15% for ovarian cancer. It is clear
      that as we learn more about the biology and the molecular aspects of hereditary
      forms of breast cancer, it will be compelling for the clinician to integrate this
      knowledge with pharmacologic, radiologic, and surgical treatment options for
      these high-risk patients.

PMID- 18086272
TI  - Hereditary breast cancer: part I. Diagnosing hereditary breast cancer syndromes.
AB  - Hereditary breast cancer (HBC) accounts for as much as 10% of the total BC
      burden. Most of these cases will be found to be due to a BRCA germline mutation.
      An estimated additional 15-20% of those affected with BC will have one or more
      first- and/or second-degree relatives with BC. Therefore, when these numbers are
      combined, familial BC risk accounts for approximately 20-25% of the total BC
      burden. However, because of the often limited information on family history in
      the etiologic assessment of BC, this may be an underestimate. Confounding factors
      include its phenotypic and genotypic heterogeneity, given the association of HBC
      with a plethora of differing cancer syndromes. Its most common occurrence is its
      association with ovarian cancer in the so-called hereditary breast-ovarian cancer
      syndrome due to BRCA1 and BRCA2 mutations. More rarely, it occurs in the Li
      Fraumeni syndrome, caused by a p53 germline mutation, in which markedly early
      onset BC is found in association with brain tumors, sarcomas, leukemia, lymphoma,
      malignant melanoma, and adrenal cortical carcinoma. Importantly, the age-adjusted
      incidence of BC in women in the United States fell sharply, by 6.7%, in 2003,
      when compared with the rate identified in 2002. We postulate that increasing
      knowledge about the genetics of BC may have partially contributed to the
      identification of high-risk patients who thereby may have benefited significantly
      from early diagnosis.

PMID- 18086273
TI  - Timed-flat infusion of 5-fluorouracil associated with docetaxel as first-line
      treatment of patients with metastatic breast cancer.

PMID- 18086274
TI  - Use of p63 and CD10 in the differential diagnosis of papillary neoplasms of the
      breast.
AB  - Papillary neoplasms of the breast represent a complex spectrum ranging from
      benign to malignant lesions. The myoepithelial cell (MEC) layer is generally
      continuous in papillomas and increasingly discontinuous to absent in atypical and
      malignant counterparts. Identification of MECs can be difficult on morphological
      grounds and currently relies on immunomarkers. We investigated the potential role
      of p63 and CD10 in 20 papillary lesions and compared them with 1A4 and calponin.
      In 18 cases, adjacent normal breast tissue was available for study. All four
      markers were diffusely positive in all samples of normal tissue and benign
      papillomas indicating similar sensitivity in the identification of MECs. Intense
      positivity was found in 100% of the cases with 1A4 and CD10, but in only 76% with
      calponin and in 60.5% with p63 (differences statistically significant, p < 0.05),
      suggesting that the former two render more reproducible results. The most
      specific markers were p63 and CD10 which showed cross-reactivity in 0% and in up
      to 33% of the cases respectively. 1A4 and calponin showed diffuse cross
      reactivity in all cases. When assessing benign versus atypical papillomas, the
      best parameters were diffuse positivity using CD10 or p63, and continuous MEC
      layer, mainly using CD10. When comparing benign papillomas to carcinomas all
      parameters were equally useful with 1A4 and CD10. Regardless of the marker,
      intense positivity was the only parameter that could distinguish atypical
      papillomas from papillary carcinomas. p63 staining, which renders a nuclear and
      mostly discontinuous reactivity, was not as useful as the other markers when the
      parameter continuous MEC layer was evaluated. Although CD10 seems to combine the
      highest specificity and reproducibility with a good sensitivity, reproducibility
      of 1A4 is higher. Thus, a minimum panel to assess papillary lesions should
      include both markers. Although p63 is the most specific, its nuclear and
      discontinuous pattern may lead to erroneous diagnosis, especially in the
      differentiation between benign papillomas and atypical/malignant lesions.

PMID- 18086275
TI  - Cytomegalovirus-associated chorioretinitis after liver transplantation: case
      report and review of the literature.
AB  - A cytomegalovirus (CMV) donor positive/recipient negative liver transplant
      recipient developed CMV syndrome with presumed colitis 2 weeks after
      discontinuing the standard 3 months of valganciclovir prophylaxis. Treatment with
      intravenous ganciclovir (GCV) reduced, but did not clear, CMV replication. A CMV
      UL97 mutation (M460V) conferring GCV resistance was identified. Reduction of
      immunosuppression was followed by rapidly rising lymphocyte counts as well as by
      clearance of CMV viremia and of clinical symptoms. However, bilateral
      chorioretinitis was diagnosed 2 weeks later and treated with foscarnet and
      cidofovir. Then, right eye vitritis occurred necessitating vitrectomy due to a
      partially rhegmatogeneous retinal detachment. Because chorioretinitis-vitritis
      after rising lymphocyte counts and clearance of CMV viremia was strongly
      suggestive of an immune reconstitution syndrome (IRS)-like disease, we
      investigated CMV-specific T-cells in the peripheral blood available during follow
      up. We found strong CD8(+) but only low CD4(+) T-cell responses (4.77% vs.<0.1%)
      to the CMV immediate early pp72, while responses to CMV-lysate or CMV-pp65
      (CD4(+) <0.01%; CD8(+)<0.01%) were low. Over 16 weeks of follow-up, pp72-specific
      CD8(+) responses declined, while responses to pp65 gradually increased (CD4(+)
      0.16%; CD8(+) 0.76%) indicating a slowly adapting CMV-specific cellular T-cell
      response. Review of 12,653 published liver transplant patients identified only 14
      (0.1%) reported cases of CMV-associated chorioretinitis at a median 41.7 weeks
      post transplant. CMV-associated opthalmologic complications late post
      transplantation may possibly involve 2 different entities of cytopathic retinitis
      and IRS-like chorioretinitis-vitritis.

PMID- 18086276
TI  - Fungal panniculitis in renal transplant recipients.
AB  - Panniculitis may result due to various etiologies. In post-transplant
      immunosuppressed patients infection is the foremost cause of panniculitis. We
      present 2 cases of fungal panniculitis in renal transplant recipients. The first
      patient presented with non-tender firm erythematous plaques on the left thigh.
      Biopsy showed panniculitis with cryptococci. Subsequent investigations revealed
      the presence of cryptococcal antigens in the blood, urine, and bronchoalveolar
      lavage fluid. There was no evidence of cryptococcal meningitis. The second
      patient complained of subcutaneous nodules on the trunk and right thigh. Biopsy
      of one of the nodules showed panniculitis with histoplasma. This patient had been
      treated earlier (inadequately) for disseminated histoplasmosis. Both the cases
      responded well to conventional amphotericin B therapy. Their renal functions
      remained stable.

PMID- 18086277
TI  - Varicella zoster virus-associated disease in adult kidney transplant recipients:
      incidence and risk-factor analysis.
AB  - Varicella zoster virus (VZV)-related disease, particularly herpes zoster, is a
      complication of organ transplantation due to long-term immunosuppression. We
      determined the incidence and risk factors for post-transplant VZV infection by
      retrospectively reviewing the medical records of a cohort of 612 adult renal
      transplant recipients transplanted at Mayo Clinic Rochester between October 1,
      2001 and October 1, 2004. Thirty-seven subjects developed herpes zoster,
      corresponding to a follow-up time-adjusted incidence of 11.2% at 4 years post
      transplant. The incidence rate of zoster was relatively constant between 6 months
      and 4 years, yielding an average incidence of approximately 28 per 1000 person
      years. The risk of developing post-transplant zoster increased with increasing
      age at transplant, with each decade conferring a 1.42-fold (P=0.009) increase in
      risk of zoster development. Seronegativity at time of transplant conferred over 3
      times the risk of development of post-transplant zoster (hazard ratio 3.4;
      P=0.04) compared with seropositivity. Adult kidney transplant recipients are at
      high risk for the development of post-transplant zoster.

PMID- 18086278
TI  - Donor-derived human herpes virus 8-related Kaposi's sarcoma in renal allograft
      ureter.
AB  - We present a case of human herpes virus 8 (HHV8)-associated Kaposi sarcoma (KS)
      occurring in a renal allograft ureter from a male donor. The female patient
      presented with a rising creatinine due to ureteric obstruction, and subsequent
      histological examination of the excised tumor revealed a KS. The tumor tested
      positive for HHV8 antigen and, using in situ hybridization to identify X and Y
      chromosomes, we were able to demonstrate that the tumor was of male origin. In
      the absence of any other KS lesions, this suggested that the tumor arose due to
      reactivation of latent HHV8 in the donor tissue, permitted by the recipient's
      immunosuppression. The patient was managed by a gradual reduction in
      immunosuppression and there has been no subsequent recurrence of the tumor. KS in
      renal transplantation is discussed in detail including the possible utility of
      pre-transplant HHV8 screening.

PMID- 18086279
TI  - Aseptic meningitis and abducens nerve palsy as a serious side effect of high dose
      intravenous immunoglobulin used in a patient with renal transplantation.
AB  - Immune globulin intravenous (human) (IGIV) is effective in the treatment of
      various autoimmune and inflammatory disorders. Recently, high-dose IGIV 2 g/kg
      has been utilized in the treatment of antibody-mediated rejection in solid organ
      transplantation. We report a renal transplant recipient who developed aseptic
      meningitis and diplopia from abducens nerve (cranial nerve VI) palsy following
      IGIV administration for antibody-mediated rejection. Potential mechanisms of the
      IGIV-related aseptic meningitis are elaborated. Clinicians should be aware of
      aseptic meningitis and cranial nerve palsy as an adverse reaction to IGIV
      exposure and monitor for its signs and symptoms.

PMID- 18086280
TI  - Fungal and mycobacterial infections after Campath (alemtuzumab) induction for
      renal transplantation.
AB  - OBJECTIVES: To report our experience with fungal and mycobacterial (tuberculosis)
      infection following induction with Campath (alemtuzumab). METHODS: We reviewed
      the database of 477 renal transplant patients induced with alemtuzumab. All those
      who had a fungal or mycobacterial infection were found, and the details of these
      complications reviewed. RESULTS: Five patients were found to have fungal (3) or
      tuberculous (2) infection. The incidence of fungal infection was 0.6% and that of
      tuberculous infection was 0.4%. Mortality rates for these 2 types of infection
      were 50% and 100%, respectively. During the same period, there was an overall
      mortality of 1.7% (n=5). No surviving patient lost graft function. CONCLUSION:
      Although fungal and mycobacterial infections caused significant mortality, the
      overall incidence remains low and comparable to that associated with other
      induction agents.

PMID- 18086281
TI  - Phytochromes and cryptochromes regulate the differential growth of Arabidopsis
      hypocotyls in both a PGP19-dependent and a PGP19-independent manner.
AB  - Photoreceptors, phytochromes and cryptochromes regulate hypocotyl growth under
      specific conditions, by suppressing negative gravitropism, modulating
      phototropism and inhibiting elongation. Although these effects seem to be
      partially caused via the regulation of the phytohormone auxin, the molecular
      mechanisms underlying this process are still poorly understood. In our present
      study, we demonstrate that the flabby mutation enhances both phytochrome- and
      cryptochrome-inducible hypocotyl bending in Arabidopsis. The FLABBY gene encodes
      the ABC-type auxin transporter, PGP19, and its expression is suppressed by the
      activation of phytochromes and cryptochromes. Our current results therefore
      indicate that the phytochromes and cryptochromes have at least two effects upon
      the tropic responses of the hypocotyls in Arabidopsis: the enhancement of
      hypocotyl bending through the suppression of PGP19, and a PGP19-independent
      mechanism that induces hypocotyl bending. By the using an auxin polar transport
      assay and DR5:GUS expression analysis, we further find that the phytochromes
      inhibit basipetal auxin transport, and induce the asymmetric distribution of
      auxin in the hypocotyls. These data suggest that the control of auxin transport
      by phytochromes and cryptochromes is a critical regulatory component of hypocotyl
      growth in response to light.

PMID- 18086282
TI  - Biosynthesis of circular proteins in plants.
AB  - Plant cyclotides are a large family of naturally occurring circular proteins that
      are produced from linear precursors containing one, two or three cyclotide
      domains. The mechanism of excision of the cyclotide domains and ligation of the
      free N- and C-termini to produce the circular peptides has not been elucidated.
      Here, we investigate production of the prototypic cyclotide kalata B1 from the
      precursor Oak1 from the African plant Oldenlandia affinis. Immunoprecipitation
      experiments and MALDI-TOF mass spectrometry analysis showed that O. affinis only
      produces mature kalata B1, whereas transgenic Arabidopsis thaliana, Nicotiana
      tabacum and Nicotiana benthamiana produced both linear and circular forms.
      Circular peptides were not produced when a highly conserved asparagine residue at
      the C-terminal processing site of the cyclotide domain was replaced with an
      alanine or an aspartate residue, or when the conserved C-terminal tripeptide
      motif was truncated. We propose that there are two processing pathways in planta:
      one to produce the mature cyclotide and the other to produce linear variants that
      ultimately cannot be cyclized.

PMID- 18086283
TI  - Phylogenetic footprints in fern spore- and seed-specific gene promoters.
AB  - Spermatophyte seed-storage proteins have descended from a group of proteins
      involved in cellular desiccation/hydration processes. Conserved protein
      structures are found across all plant phyla and in the fungi and Archaea. We
      investigated whether conservation in the coding region sequence is paralleled by
      common gene regulatory processes. Seed- and spore-specific gene promoters of
      three phylogenetically diverse plants were analysed by transient and transgenic
      expression in Arabidopsis thaliana and tobacco. The transcription factors FUS3
      and ABI3, which are central regulators of seed maturation processes, interact
      with cis-motifs of seed-specific promoters from distantly related plants. The
      promoter of a fern spore-specific gene encoding a seed-storage globulin-like
      protein exhibits strong seed-specific activity in both Arabidopsis and tobacco.
      The existence of phylogenetic footprints indicates good conservation of
      regulatory pathways controlling gene expression in fern spores and in gymnosperm
      and angiosperm seeds, reflecting the concerted evolution of coding and regulatory
      regions.

PMID- 18086284
TI  - Rapid spatiotemporal patterning of cytosolic Ca2+ underlies flagellar excision in
      Chlamydomonas reinhardtii.
AB  - Ca(2+)-dependent signalling processes are implicated in many aspects of flagella
      function in the green alga, Chlamydomonas. In this study, we examine the
      spatiotemporal dynamics of cytosolic Ca2+ ([Ca2+](cyt)) in single Chlamydomonas
      cells during the process of flagellar excision, using biolistically loaded
      calcium-responsive dyes. Acid-induced deflagellation occurred in parallel with a
      single transient elevation in whole-cell [Ca2+](cyt), which was absent in the
      acid deflagellation-deficient adf1 mutant. Deflagellation could also be induced
      by elevated external Ca2+ ([Ca2+](ext)), which promoted very rapid spiking of
      [Ca2+](cyt) across the whole cell and in the flagella. We also detected very
      rapid apically localised Ca2+ signalling events with an approximate duration of
      500 msec. Ninety-seven per cent of deflagellation events coincided with a rapid
      elevation in [Ca2+](cyt) in the apical region of the cell, either in the form of
      a whole cell or an apically localised increase, indicating that [Ca2+](cyt)
      elevations in the apical region play an underlying role in deflagellation. Our
      data indicate that elevated [Ca2+](ext) acts to disrupt Ca2+ homeostasis which
      induces deflagellation by both Adf1-dependent and Adf1-independent mechanisms.
      Elevated [Ca2+](ext) also results in further [Ca2+](cyt) elevations after the
      main period of whole cell spiking which are very strongly associated with
      deflagellation, exhibit a high degree of apical localisation and are largely
      absent in the adf1 mutant. We propose that these later elevations may act as
      specific signals for deflagellation.

PMID- 18086285
TI  - Transplant recipient renal function is donor renal mass- and recipient gender
      dependent.
AB  - The effect of both donor renal mass and gender on renal function, in both gender
      recipients, was examined. Qualifying consecutive living-donor renal transplants
      (n = 730) were stratified into 4 donor-recipient groups: female-female (n = 177),
      male-female (n = 151), female-male (n = 240), male-male (n = 162). Groups were
      equivalent in age, race, body mass index (BMI), match, ischemia time, operative
      time, and estimated glomerular filtration rate (eGFR). Female recipients had
      lower serum creatinine (Cr(s)). Male recipients had higher Cr(s) wherever they
      received a female allograft. Male recipients of male kidneys had a higher eGFR
      than all other groups for 3 years. Renal function of the recipient correlated
      with the renal mass of the donor within each group. Male and female kidneys
      functioned equivalently in the female-recipient environment. Large nephron-mass
      male donor kidneys function more poorly in female recipients. The male kidney
      loses 15-20 ml/min eGFR in the female host. The diminished graft function may be
      related to androgen deprivation. Female and male donor kidneys function
      equivalently in the male recipient if adjusted for renal mass transplanted.
      Female kidneys improve eGFR by 7-10 ml/min by being transplanted into a male
      environment. Donor renal mass and gender affect recipient graft function
      Expectations of ultimate recipient renal function should take into account both
      the gender and mass disparity of the donor-recipient pair.

PMID- 18086286
TI  - Screening for sickle trait among potential live kidney donors: policies and
      practices in US transplant centers.
AB  - Sickle cell trait is common in the United States (US) and associated with
      abnormalities of renal function. Little is known, however, about the potential
      risk of sickle cell trait to live kidney donors. Using an original questionnaire,
      we assessed the policies and practices of US renal transplant centers with regard
      to screening for sickle trait among potential live kidney donors. Fifty-four
      percent (137/252) of centers responded. Eighty-three percent (113/137) of
      transplant centers had no policy to screen donors for sickle trait. Thirty-four
      percent (46/135) of centers reported actually screening donors for sickle trait
      in practice. Thirty-seven percent (39/105) of centers reported excluding donors
      with sickle trait always or most of the time. High volume centers (>100 live
      donor transplants/year) were more likely to screen for sickle trait (Fisher's
      exact, P = 0.03), but not more likely to exclude potential donors with sickle
      trait from donating. Most US renal transplant centers do not screen donors for
      sickle trait. Wide variation is evident in center practice regarding exclusion of
      donors on the basis of sickle trait. Research into the potential impact of sickle
      trait on renal function after donation is needed to guide transplant clinicians.

PMID- 18086287
TI  - Sequences variations in 5'-flanking region of ABO gene and correlation with ABO
      alleles in the indigenous Chinese.
AB  - BACKGROUND AND OBJECTIVES: 5'-flanking sequences of the ABO gene play important
      role in the regulation of gene expression, but polymorphism of 5'-flanking
      sequence of ABO gene is rarely known. Here, we further characterize the molecular
      genetic basis and ABO allele-related polymorphism of the 5'-untranslated regions
      (5'-UTR) of the human ABO gene. MATERIALS AND METHODS: Collecting blood samples
      from 72 blood donors in Hangzhou, China, we analysed sequences of exons 6 and 7
      of ABO gene and amplified an enhanced segment of 43 bp repeats in the 5'-UTR.
      Subsequently, we selected 25 homozygotes [of genotypes A101/A101 (two), A102/A102
      (seven), B101/B101 (seven) and O01/O01 (nine)] and five heterozygotes [A102/O01
      (two), B101/O01 (two) and O01/O105 (one)] for sequencing 5 -kb amplicons spanning
      the 5'-UTR and partial exon 1 of the ABO gene. We sequenced the amplicons
      bidirectionally and, when pertinent, analysed selected haplotypes by cloning.
      RESULTS: As a result, we identified 11 new polymorphic sites (10 point mutations,
      one 8-bp deletion) in the 5'-UTR of the A102, B101 and O01 alleles of common ABO
      phenotypes. Five A102 alleles carry four tandem repeats of a 43-bp minisatellite
      unit that deviated from previous reports. CONCLUSION: The results revealed the
      DNA polymorphisms in the 5'-UTRs correlated with the common ABO alleles.
      Elucidation of the diversity of the 5'-UTRs is an important supplement to
      existing methods for increasing our understanding of the molecular basis of the
      ABO blood group system.

PMID- 18086288
TI  - Propionibacterium acnes lacks the capability to proliferate in platelet
      concentrates.
AB  - BACKGROUND AND OBJECTIVES: Propionibacterium acnes is considered to be one of the
      most frequent contaminants of platelet concentrates (PCs) when anaerobic culture
      based detection methods are used. But Propionibacteria are often detected too
      late when blood products have already been transfused. Therefore, its transfusion
      relevance is still demanding clarification because studies of the outcome of
      patients transfused with P. acnes-contaminated PCs are still uncommon. In this
      study, we monitored clinical effects in patients after transfusion of PCs, which
      were detected too late in sterility testing. Furthermore, we assessed the
      bacterial proliferation of Propionibacterium species seeded into PCs to clarify
      their significance for platelet bacteria screening. MATERIALS AND METHODS: In the
      look-back process, we followed the route of the putative contaminated PC units
      from storage to transfusion. In the in vitro study, PCs were inoculated with 1
      100 colony-forming unit (CFU)/ml of clinical isolates of Propionibacteria (n =
      10). Sampling was performed during 10-day aerobic storage at 22 degrees C. The
      presence of bacteria was assessed by plating culture and automated BacT/Alert
      culture system. RESULTS: Propionibacterium acnes shows slow or no growth under PC
      storage conditions. Clinical signs of adverse events after transfusion of
      potentially contaminated PC units were not reported. CONCLUSION: Propionibacteria
      do not proliferate under PC storage conditions and therefore may be missed or
      detected too late when blood products have already been transfused.

PMID- 18086289
TI  - Permissive environment in postnatal wounds induced by adenoviral-mediated
      overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar
      formation.
AB  - Wound healing in the mid-gestation fetus is scarless with minimal inflammation
      and a unique extracellular matrix. We have previously documented the relative
      lack of inflammatory cytokines in this environment. We demonstrate that
      interleukin (IL)-10 is highly expressed in mid-gestation human fetal skin but is
      absent in postnatal human skin. We hypothesize that overexpression of IL-10 in
      postnatal skin may replicate a permissive environment for scarless healing. To
      study the mechanism underlying this process we performed immunohistochemistry for
      IL-10 in human mid-gestation fetal and postnatal skin. We also determined if
      adenoviral-mediated overexpression of IL-10 could allow for scarless wound
      healing in a murine incisional wound model. Wounds were analyzed at 1-90 days
      postwounding for effects on scar formation, inflammatory response, and
      biomechanical properties. Ad-IL-10 reconstitutes a permissive environment for
      scarless healing as shown by reconstitution of a normal dermal reticular collagen
      pattern and distribution of dermal elements. Compared with controls, Ad-IL-10
      treated wounds showed reduced inflammatory response and no difference in
      biomechanical parameters. Therefore, overexpression of IL-10 in postnatal wounds
      results in a permissive environment for scarless wound repair, possibly by
      replicating a fetal wound environment.

PMID- 18086290
TI  - Influence of external forces (pressure and shear force) on superficial layer and
      subcutis of porcine skin and effects of dressing materials: are dressing
      materials beneficial for reducing pressure and shear force in tissues?
AB  - The purpose of this study was to measure the impact of external shear force and
      pressure on a superficial layer of skin and subcutaneous layer with an underlying
      bony prominence, and also to verify how the influence of these external forces
      can be reduced after dressings are applied. For this purpose, an experimental
      model was prepared, consisting of porcine skin and a Predia sensor capable of
      measuring pressure and shear force simultaneously. External force was applied to
      the skin model using a 1 kg weight consisting of metal beads. As a result, the
      control of the shear force value in the subcutaneous layer became approximately
      35% smaller than the control in the superficial layer. The shear forces present
      in the subcutaneous layer were significantly reduced to within 31-45% when
      compared with the control values, depending on the dressing applied. Regarding
      the maximum pressures in the subcutaneous layer, the pressure measured following
      movement was 2.4 times higher in the control than the static pressure and they
      were also 1.3-1.8 times higher than the static pressure in all instances with the
      dressing tested. All the dressing materials tested proved to be effective in
      reducing pressure in the subcutaneous layer compared with the control. Film
      dressings and hydrocolloid dressings were more effective than hydropolymer and
      hydrocellular dressings. From the above results, we conclude that efforts made to
      reduce shear force and pressure may be clinically important.

PMID- 18086292
TI  - Effect of nerve growth factor and keratinocyte growth factor on wound healing of
      the sinus mucosa.
AB  - The healing of the sinuses after sinus surgery is often compromised by the
      development of adhesions. The aim of this study was to determine whether nerve
      growth factor (NGF) and keratinocyte growth factor (KGF) aid epithelial and
      fibroblast wound healing after surgery. Two in vitro models were used to compare
      their effect on wound closure rates and expression of cell adhesion (E-cadherin),
      tight junction formation (zona occludens-1), cell proliferation (proliferative
      cell nuclear antigen and Ki67), and ciliogenesis (Foxj1 and beta tubulin IVb)
      genes by real-time reverse transcription polymerase chain reaction. Epithelial
      cells from sinonasal tissue were seeded in collagen-coated Transwells, creating
      an air-liquid interface, and a submergent model was used for fibroblasts. In
      epithelial cells, NGF (20-50 ng/mL) significantly decreased wound areas to <40%
      compared with controls that were still 70% of their original sizes by 24 hours
      (p<0.05). E-cadherin and zona occludens-1 expression were up-regulated by 20- and
      2.5-fold, respectively, relative to controls. KGF (5-100 ng/mL) slowed fibroblast
      proliferation by reducing (0.8-fold) and Ki67 (0.25-fold) expression. NGF (10
      ng/mL) slowed Ki67 expression by 0.5-fold. NGF accelerated in vitro epithelial
      wound closure while NGF and KGF reduced fibroblast proliferation.

PMID- 18086293
TI  - Temporal and quantitative profiles of growth factors and metalloproteinases in
      acute wound fluid after mastectomy.
AB  - Seventy-three samples of acute wound fluid were collected from 47 patients during
      the first 3 postoperative days (POD) following mastectomy for cancer (n=47 on POD
      1, n=19 on POD-2, and n=7 POD-3). Samples were analyzed by enzyme-linked
      immunosorbent assay for growth factor levels (epidermal [EGF], platelet-derived
      [PDGF], basic fibroblast [bFGF], transforming growth factor-beta1 [TGF-beta1],
      vascular endothelial [VEGF]), interleukin-6 (IL-6), matrix metalloproteinases
      (MMPs-2, -3, -9), and the tissue inhibitor of metalloproteinase 1 (TIMP-1). The
      levels of EGF, bFGF, PDGF, and interleukin-6 peaked on POD-1, with a significant
      decrease by POD-3, while total and active MMP-2, MMP-3, and tissue inhibitor of
      metalloproteinase 1 showed a progressive and significant increase from days 1 to
      3. The wounds that later developed an infection (11%) were found to have a
      significantly lower PDGF and EGF on day 1 (PDGF, median 169 pg/mL [range, 86
      2,595]) than the noninfected wounds (2,098 [17-66,506] p<0.05, Mann-Whitney U
      test). Sixty-two percent patients developed a seroma and the levels of bFGF were
      significantly less in these patients (441 pg/mL [45-4,108]) than in those
      patients where there was no seroma (807 [245-3,133] p<0.05). The levels of
      certain growth factors in acute wound fluid may be important markers for wound
      outcomes.

PMID- 18086294
TI  - Biofilms in chronic wounds.
AB  - Chronic wounds including diabetic foot ulcers, pressure ulcers, and venous leg
      ulcers are a worldwide health problem. It has been speculated that bacteria
      colonizing chronic wounds exist as highly persistent biofilm communities. This
      research examined chronic and acute wounds for biofilms and characterized
      microorganisms inhabiting these wounds. Chronic wound specimens were obtained
      from 77 subjects and acute wound specimens were obtained from 16 subjects.
      Culture data were collected using standard clinical techniques. Light and
      scanning electron microscopy techniques were used to analyze 50 of the chronic
      wound specimens and the 16 acute wound specimens. Molecular analyses were
      performed on the remaining 27 chronic wound specimens using denaturing gradient
      gel electrophoresis and sequence analysis. Of the 50 chronic wound specimens
      evaluated by microscopy, 30 were characterized as containing biofilm (60%),
      whereas only one of the 16 acute wound specimens was characterized as containing
      biofilm (6%). This was a statistically significant difference (p<0.001).
      Molecular analyses of chronic wound specimens revealed diverse polymicrobial
      communities and the presence of bacteria, including strictly anaerobic bacteria,
      not revealed by culture. Bacterial biofilm prevalence in specimens from chronic
      wounds relative to acute wounds observed in this study provides evidence that
      biofilms may be abundant in chronic wounds.

PMID- 18086295
TI  - Site-specific production of TGF-beta in oral mucosal and cutaneous wounds.
AB  - Wound healing in the oral mucosa is clinically distinguished by rapid healing and
      lack of scar formation compared with dermal wounds. Mechanisms of favorable
      mucosal healing are yet to be elucidated. Utilizing a murine model of equivalent
      size mucosal and skin wounds, we verified the rapid reepithelializaton and
      reduction in scarring of oral wounds reported in humans. Collagen fibrillar
      structure in oral wounds rapidly approached the size of normal collagen fibrils,
      while the collagen ultrastructure in skin remained immature through the later
      phases of healing. To determine whether the transforming growth factor-beta (TGF
      beta) contributes to the lack of scar formation in oral mucosa, we compared the
      expression and production in oral and skin wounds. The RNase protection assay
      demonstrated significantly lower levels of TGF-beta1 expression in oral wounds
      compared with dermal wounds, and no changes were observed in the expression
      levels of TGF-beta2 or TGF-beta 3. ELISA analysis confirmed that oral wounds
      contained lower levels of TGF-beta1 levels compared with dermal wounds, along
      with a significant increase in the ratio of TGF-beta 3 to -beta1. These findings
      showed reduced scarring in oral wounds at the ultrastructural level, and provide
      evidence that site-specific differences in TGF-beta production contributes to the
      superior healing of oral wounds.

PMID- 18086296
TI  - A familial concurrence of schizophrenia and Gaucher's disease.
AB  - BACKGROUND: Gaucher's disease (GD) is the most frequently encountered lysosomal
      storage disease. Here, we describe and discuss the observed concurrence of
      schizophrenia and Gaucher's disease in two siblings. METHODS: Presentation of a
      family with two siblings with Gaucher's disease. RESULTS: In a six-member family,
      the first son suffers from schizophrenia, while the third and fourth sons suffer
      from the Gaucher's disease (type 1 non-neuronopathic). The parents and the second
      son do not suffer from either illness. CONCLUSION: The concurrence of
      schizophrenia and Gaucher's disease in the same family is an unusual phenomenon.
      The literature regarding this coincidence is limited, despite the fact that
      patients with Gaucher's disease have one or two mutated alleles, considered to be
      a risk factor leading to conditions such as Dementia, Parkinson's disease and
      schizophrenia.

PMID- 18086298
TI  - Complement activation in Ghanaian children with severe Plasmodium falciparum
      malaria.
AB  - BACKGROUND: Severe anaemia (SA), intravascular haemolysis (IVH) and respiratory
      distress (RD) are severe forms of Plasmodium falciparum malaria, with RD reported
      to be of prognostic importance in African children with malarial anaemia.
      Complement factors have been implicated in the mechanism leading to excess
      anaemia in acute P. falciparum infection. METHODS: The direct Coombs test (DCT)
      and flow cytometry were used to investigate the mean levels of RBC-bound
      complement fragments (C3d and C3balphabeta) and the regulatory proteins
      [complement receptor 1 (CD35) and decay accelerating factor (CD55)] in children
      with discrete clinical forms of P. falciparum malaria. The relationship between
      the findings and clinical parameters including coma, haemoglobin (Hb) levels and
      RD were investigated. RESULTS: Of the 484 samples tested, 131(27%) were positive
      in DCT, out of which 115/131 (87.8%) were positive for C3d alone while 16/131
      (12.2%) were positive for either IgG alone or both. 67.4% of the study population
      were below 5 years of age and DCT positivity was more common in this age group
      relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2
      6.7, p < 0.001). DCT correlated significantly with RD (beta = -304, p = 0.006),
      but multiple regression analysis revealed that, Hb (beta = -0.341, p = 0.012) and
      coma (beta = -0.256, p = 0.034) were stronger predictors of RD than DCT (beta =
      0.228, p = 0.061). DCT was also not associated with IVH, p = 0.19, while spleen
      size was inversely correlated with Hb (r = -402, p = 0.001). Flow cytometry
      showed similar mean fluorescent intensity (MFI) values of CD35, CD55 and
      C3balphabeta levels on the surfaces of RBC in patients and asymptomatic controls
      (AC). However, binding of C3balphabeta correlated significantly with CD35 or CD55
      (p < 0.001). CONCLUSION: These results suggest that complement activation
      contributed to anaemia in acute childhood P. falciparum malaria, possibly through
      induction of erythrophagocytosis and haemolysis. In contrast to other studies,
      this study did not find association between levels of the complement regulatory
      proteins, CD35 and CD55 and malarial anaemia. These findings suggest that
      complement activation could also be involved in the pathogenesis of RD but larger
      studies are needed to confirm this finding.

PMID- 18086297
TI  - Sequence analysis of Plasmodium falciparum cytochrome b in multiple geographic
      sites.
AB  - BACKGROUND: The antimalarial drug atovaquone specifically targets Plasmodium
      falciparum cytochrome b (Pfcytb), a mitochondrial gene with uniparental
      inheritance. Cases of resistance to atovaquone associated with mutant Pfcytb have
      been reported, justifying efforts to better document the natural polymorphism of
      this gene. To this end, a large molecular survey was conducted in several malaria
      endemic areas where atovaquone was not yet in regular use. METHODS: The
      polymorphism of the Pfcytb was analysed by direct sequencing of PCR products
      corresponding to the full length coding region. Sequence was generated for 671
      isolates originating from three continents: Africa (Senegal, Ivory Coast, Central
      African Republic and Madagascar), Asia (Cambodia) and South America (French
      Guiana). RESULTS: Overall, 11 polymorphic sites were observed, of which eight
      were novel mutations. There was a large disparity in the geographic distribution
      of the mutants. All isolates from Senegal, Central African Republic and
      Madagascar displayed a Camp/3D7 wild type Pfcytb sequence, as did most samples
      originating from Cambodia and Ivory Coast. One synonymous (t759a at codon V253V)
      and two non-synonymous (t553g and a581g at codons F185V and H194R, respectively)
      singletons were detected in Ivory Coast. Likewise, two synonymous (a126t and
      c793t at codons -T42T and L265L, respectively) singletons were observed in
      Cambodia. In contrast, seven mutated sites, affecting seven codons and defining
      four mutant haplotypes were observed in French Guiana. The wild type allele was
      observed in only 14% of the French Guiana isolates. The synonymous c688t mutation
      at position L230L was highly prevalent; the most frequent allele was the c688t
      single mutant, observed in 84% of the isolates. The other alleles were singletons
      (a126t/a165c, a4g/a20t/a1024c and a20t/t341c/c688t corresponding to T42T/S55S,
      N2D/N71I/I342L, N71I/L114S/L230L, respectively" please replace with '
      corresponding to T42T/S55S, N2D/N71I/I342L and N71I/L114S/L230L, respectively).
      The codon 268 polymorphisms associated with atovaquone resistance were not
      observed in the panel the isolates studied. Overall, the wild type PfCYTb protein
      isoform was highly predominant in all study areas, including French Guiana,
      suggesting stringent functional constraints. CONCLUSION: These data along with
      previously identified Pfcytb field polymorphisms indicate a clustering of
      molecular signatures, suggesting different ancestral types in South America and
      other continents. The absence of mutations associated with most atovaquone
      proguanil clinical failures indicates that the atovaquone-proguanil association
      is an interesting treatment option in the study areas.

PMID- 18086299
TI  - CD40 signaling predicts response to preoperative trastuzumab and concomitant
      paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2
      overexpressing breast cancer.
AB  - INTRODUCTION: We performed gene expression analysis to identify molecular
      predictors of resistance to preoperative concomitant trastuzumab and paclitaxel
      followed by 5-fluorouracil, epirubicin, and cyclophosphamide (T/FEC). METHODS:
      Pretreatment fine-needle aspiration specimens from 45 patients with HER-2
      overexpressing stage II to IIIA breast cancer were subjected to transcriptional
      profiling and examined for differential expression of various genes and gene
      sets. The primary endpoint for tumor response was pathologic complete response
      (pCR). Correlations between pCR and gene expression were sought. RESULTS: The
      overall pCR rate was 64%. Age, nuclear grade, tumor size, nodal status,
      quantitative expression of estrogen and HER-2 receptor mRNA, and HER-2 gene copy
      number showed no correlation with pCR. Results of gene set enrichment analysis
      suggested that the lower expression of genes involved with CD40 signaling is
      associated with a greater risk of residual cancer after the preoperative
      chemotherapy that includes trastuzumab. CONCLUSION: CD40 signaling may play a
      role in determining response to trastuzumab-plus-T/FEC therapy in patients with
      HER-2-overexpressing breast cancer.

PMID- 18086300
TI  - The role of resuscitation promoting factors in pathogenesis and reactivation of
      Mycobacterium tuberculosis during intra-peritoneal infection in mice.
AB  - BACKGROUND: Mycobacterium tuberculosis can enter into a dormant state which has
      resulted in one third of the world's population being infected with latent
      tuberculosis making the study of latency and reactivation of utmost importance.
      M. tuberculosis encodes five resuscitation promoting factors (Rpfs) that bear
      strong similarity to a lysozyme-like enzyme previously implicated in reactivation
      of dormant bacteria in vitro. We have developed an intraperitoneal infection
      model in mice, with immune modulation, that models chronic infection with similar
      properties in mouse lungs as those observed in the murine aerosol infection
      model. We have assessed the behavior of mutants that lack two or three rpf genes
      in different combinations in our intraperitoneal model. METHODS: C57Bl/6 mice
      were intraperitonealy infected with H37Rv wild type M. tuberculosis or mutant
      strains that lacked two or three rpf genes in different combinations. After 90
      days of infection aminoguanidine (AG) or anti-TNFalpha antibodies were
      administrated. Organ bacillary loads were determined at various intervals post
      infection by plating serial dilutions of organ homogenates and enumerating
      bacteria. RESULTS: We found that the rpf triple and double mutants tested were
      attenuated in their ability to disseminate to mouse lungs after intraperitoneal
      administration and were defective in their ability to re-grow after
      immunosuppression induced by administration of aminoguanidine and anti-TNFalpha
      antibodies. CONCLUSION: Rpf proteins may have a significant physiological role
      for development of chronic TB infection and its reactivation in vivo.

PMID- 18086301
TI  - An oncoplastic technique to reduce the formation of lateral 'dog-ears' after
      mastectomy.
AB  - BACKGROUND: Lateral skin folds or 'dog-ears' are frequent following mastectomy,
      particularly in patients with large body habitus. METHODS: We describe a method
      of modifying the mastectomy incision and suturing to eliminate these lateral 'dog
      ears'. CONCLUSION: This surgical technique, as compared to others described in
      the literature, is simple, does not require additional incisions and is
      cosmetically acceptable to the patient.

PMID- 18086302
TI  - Human periostin gene expression in normal tissues, tumors and melanoma: evidences
      for periostin production by both stromal and melanoma cells.
AB  - BACKGROUND: Recently, periostin (POSTN), a gene encoding a protein with
      similarity to the fasciclin family and involved in cell survival and
      angiogenesis, has emerged as a promising marker for tumor progression in various
      types of human cancers. There is some controversy regarding both POSTN expression
      levels and the nature of periostin-producing cells within tumors. In this study,
      we used quantitative RT-PCR to assess periostin gene expression in normal
      tissues, primary cell cultures, tumor tissues and tumor cell lines. RESULTS:
      Periostin expression levels are highly variable in both normal tissues and tumors
      and strong POSTN overexpression is mostly detected in tumors from pancreas and
      liver. POSTN is not expressed in blood cancers. In melanoma samples, average
      periostin expression is not increased in primary tumors whereas POSTN
      overexpression was detected in about 60% of melanoma metastatic tumors in the
      liver or lymph nodes. Identification of the cellular source of periostin
      production in melanoma metastases -cancer cells or stroma- was assessed by
      comparing periostin expression in 23 newly-established melanoma cell lines and
      matched tumors. In contrast to the reduction by more than 99% of COL6A3 stromal
      marker mRNA in all cell lines, significant POSTN transcription was maintained in
      some melanoma cell lines, suggesting that both stromal cells and melanoma cells
      express periostin. The high level of periostin expression in primary cultures of
      skin fibroblasts suggests that fibroblasts may contribute for a large part to
      periostin production in melanoma-associated stroma. On the other hand, periostin
      expression in melanoma cells is probably acquired during the tumorigenic process
      as 1) normal melanocytes do not express POSTN and 2) melanoma cells from distinct
      metastases of the same patient were associated with very different levels of
      periostin expression. CONCLUSION: Our comparative analysis suggests that,
      although periostin overexpression is clearly detected in some cancers, it is not
      a general feature of tumors. In melanoma, our study identifies both stromal and
      melanoma cells as sources of periostin production and correlates POSTN expression
      levels with increased primary tumor thickness and metastatic process development.

PMID- 18086303
TI  - Does the history of food energy units suggest a solution to "Calorie confusion"?
AB  - The Calorie (kcal) of present U.S. food labels is similar to the original French
      definition of 1825. The original published source (now available on the internet)
      defined the Calorie as the quantity of heat needed to raise the temperature of 1
      kg of water from 0 to 1 degrees C. The Calorie originated in studies concerning
      fuel efficiency for the steam engine and had entered dictionaries by 1840. It was
      the only energy unit in English dictionaries available to W.O. Atwater in 1887
      for his popular articles on food and tables of food composition. Therefore, the
      Calorie became the preferred unit of potential energy in nutrition science and
      dietetics, but was displaced when the joule, g-calorie and kcal were introduced.
      This article will explain the context in which Nicolas Clement-Desormes defined
      the original Calorie and the depth of his collaboration with Sadi Carnot. It will
      review the history of other energy units and show how the original Calorie was
      usurped during the period of international standardization. As a result, no form
      of the Calorie is recognized as an SI unit. It is untenable to continue to use
      the same word for different thermal units (g-calorie and kg-calorie) and to use
      different words for the same unit (Calorie and kcal). The only valid use of the
      Calorie is in common speech and public nutrition education. To avoid ongoing
      confusion, scientists should complete the transition to the joule and cease using
      kcal in any context.

PMID- 18086304
TI  - Use of comparative data for integrated cancer services.
AB  - BACKGROUND: Comparative data are an important resource for management of
      integrated care. In 2001, the English Department of Health created 34 cancer
      networks, broadly serving populations of half to three million people, to
      coordinate cancer services across providers. We have investigated how national
      and regional routine data are used by the cancer network management teams.
      METHODS: Telephone interviews using a standardised semi-structured questionnaire
      were conducted with 68 participants in 29 cancer network teams. Replies were
      analysed both quantitatively and qualitatively. RESULTS: While most network teams
      had a formal information strategy, data were used ad hoc more than regularly, and
      were not thought to be as influential in network decision making as other sources
      of information. Data collection was more prominent in information strategies than
      data use. Perceptions of data usefulness were mixed and there were worries over
      data quality, relevance, and potential misuse. Participants were receptive to the
      idea of a new limited dataset collating comparative data from currently available
      routine data sources. Few network structural factors were associated with data
      use, perceptions of current data, or receptivity to a new dataset. CONCLUSION:
      Comparative data are underused for managing integrated cancer services in
      England. Managers would welcome more comparative data, but also desired data to
      be relevant, quality assured and contextualised, and for the teams to be better
      resourced for data use.

PMID- 18086307
TI  - Prediction of posttraumatic stress in fathers of children with chronic diseases
      or unintentional injuries: a six-months follow-up study.
AB  - BACKGROUND: While fathers were neglected for a long time in research
      investigating families of pediatric patients, there are now a few studies
      available on fathers' posttraumatic stress symptoms (PTSS) and posttraumatic
      stress disorder (PTSD). However, little is known about the course of PTSS and
      PTSD in fathers of pediatric patients. The present study aimed to compare the
      prevalence and course of PTSS and PTSD in fathers of children with different
      chronic and acute conditions and to identify factors that contribute to fathers'
      PTSS. METHODS: Sixty-nine fathers of children newly diagnosed with either cancer,
      type I diabetes mellitus, or epilepsy and 70 fathers of children suffering from
      an unintentional injury completed questionnaires at 4-6 weeks (Time 1) and six
      months (Time 2) after diagnosis or injury. RESULTS: Noticeable PTSD rates were
      found in fathers of children with a chronic disease (26% at Time 1 and 21% at
      Time 2, respectively). These rates were significantly higher than rates found in
      fathers of children with unintentional injuries (12% at Time 1 and 6% at Time 2,
      respectively). Within six months after the child's diagnosis or accident a
      decrease in severity of PTSS was observed in both groups. Significant predictors
      of PTSS at Time 2 were the father's initial level of PTSS, the child's medical
      condition (injuries vs. chronic diseases) and functional status, the father's use
      of dysfunctional coping strategies, and father's level of neuroticism.
      CONCLUSION: Our findings suggest that fathers with initially high PTSS levels are
      at greater risk to experience PTSS at follow-up, particularly fathers of children
      with a chronic disease. Sensitizing health care professionals to the
      identification of PTSS symptoms but also to indicators of neuroticism and the use
      of specific coping strategies early in the treatment course is essential for the
      planning and implementation of adequate intervention strategies.

PMID- 18086306
TI  - Haemoglobin and haematocrit: the threefold conversion is also non valid for
      assessing anaemia in Plasmodium vivax malaria-endemic settings.
AB  - It has been recently reported that the standard threefold conversion from
      haematocrit to haemoglobin underestimates the prevalence of anaemia and low
      levels of haemoglobin in children living in areas endemic for Plasmodium
      falciparum malaria. The data presented herein describes the experience in a
      malaria-endemic zone in northeastern Venezuela (state of Sucre), where a similar
      bias between haematocrit and haemoglobin in patients with Plasmodium vivax
      infection was found. In summary, the relationship between haematocrit and
      haemoglobin needs to be specifically evaluated according to each particular
      region or epidemiological setting.

PMID- 18086305
TI  - HBVRegDB: annotation, comparison, detection and visualization of regulatory
      elements in hepatitis B virus sequences.
AB  - BACKGROUND: The many Hepadnaviridae sequences available have widely varied
      functional annotation. The genomes are very compact (approximately 3.2 kb) but
      contain multiple layers of functional regulatory elements in addition to coding
      regions. Key regions are subject to purifying selection, as mutations in these
      regions will produce non-functional viruses. RESULTS: These genomic sequences
      have been organized into a structured database to facilitate research at the
      molecular level. HBVRegDB is a comparative genomic analysis tool with an
      integrated underlying sequence database. The database contains genomic sequence
      data from representative viruses. In addition to INSDC and RefSeq annotation,
      HBVRegDB also contains expert and systematically calculated annotations (e.g.
      promoters) and comparative genome analysis results (e.g. blastn, tblastx). It
      also contains analyses based on curated HBV alignments. Information about
      conserved regions - including primary conservation (e.g. CDS-Plotcon) and RNA
      secondary structure predictions (e.g. Alidot) - is integrated into the database.
      A large amount of data is graphically presented using the GBrowse (Generic Genome
      Browser) adapted for analysis of viral genomes. Flexible query access is provided
      based on any annotated genomic feature. Novel regulatory motifs can be found by
      analysing the annotated sequences. CONCLUSION: HBVRegDB serves as a knowledge
      database and as a comparative genomic analysis tool for molecular biologists
      investigating HBV. It is publicly available and complementary to other viral and
      HBV focused datasets and tools http://hbvregdb.otago.ac.nz. The availability of
      multiple and highly annotated sequences of viral genomes in one database combined
      with comparative analysis tools facilitates detection of novel genomic elements.

PMID- 18086310
TI  - Pitfalls in diagnosing a small cystic insulinoma: a case report.
AB  - Insulinoma is a rare pancreatic endocrine tumour and is typically sporadic and
      solitary. Over 90% of all insulinomas are benign. Cystic insulinomas are also
      rare. It is not difficult to determine the site of such neoplasm, as cystic
      insulinomas are usually 4-10 cm in diameter. We present the case of a patient
      with a histologically confirmed cystic insulinoma diagnosed after approximately
      10 years of hypoglycaemia symptoms. This case is unique because of the small size
      (2.2 cm) of the tumour. Endoscopic ultrasound (EUS) was useful for localizing
      this tumour.

PMID- 18086308
TI  - Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient
      receptor potential ankyrin 1 (TRPA1) antagonists.
AB  - Agonists of TRPA1 such as mustard oil and its key component AITC cause pain and
      neurogenic inflammation in humans and pain behavior in rodents. TRPA1 is
      activated by numerous reactive compounds making it a sensor for reactive
      compounds in the body. Failure of AITC, formalin and other reactive compounds to
      trigger pain behavior in TRPA1 knockout mice, as well as the ability of TRPA1
      antisense to alleviate cold hyperalgesia after spinal nerve ligation, suggest
      that TRPA1 is a potential target for novel analgesic agents. Here, we have
      characterized CHO cells expressing human and rat TRPA1 driven by an inducible
      promoter. As reported previously, both human and rat TRPA1 are activated by AITC
      and inhibited by ruthenium red. We have also characterized noxious cold response
      of these cell lines and show that noxious cold activates both human and rat
      TRPA1. Further, we have used CHO cells expressing human TRPA1 to screen a small
      molecule compound library and discovered that 'trichloro(sulfanyl)ethyl
      benzamides' (AMG2504, AMG5445, AMG7160 and AMG9090) act as potent antagonists of
      human TRPA1 activated by AITC and noxious cold. However, trichloro(sulfanyl)ethyl
      benzamides' (TCEB compounds) displayed differential pharmacology at rat TRPA1.
      AMG2504 and AMG7160 marginally inhibited rat TRPA1 activation by AITC, whereas
      AMG5445 and AMG9090 acted as partial agonists. In summary, we conclude that both
      human and rat TRPA1 channels show similar AITC and noxious cold activation
      profiles, but TCEB compounds display species-specific differential pharmacology
      at TRPA1.

PMID- 18086309
TI  - Health-related quality of life and long-term prognosis in chronic hypercapnic
      respiratory failure: a prospective survival analysis.
AB  - BACKGROUND: Health-related quality of life (HRQL) is considered as an important
      outcome parameter in patients with chronic diseases. This study aimed to assess
      the role of disease-specific HRQL for long-term survival in patients of different
      diagnoses with chronic hypercapnic respiratory failure (CHRF). METHODS: In a
      cohort of 231 stable patients (chronic obstructive pulmonary disease (COPD), n =
      98; non-COPD (obesity-hypoventilation syndrome, restrictive disorders,
      neuromuscular disorders), n = 133) with CHRF and current home mechanical
      ventilation (HMV), HRQL was assessed by the disease-specific Severe Respiratory
      Insufficiency (SRI) questionnaire and its prognostic value was prospectively
      evaluated during a follow-up of 2-4 years, using univariate and multivariate
      regression analysis. RESULTS: HRQL was more impaired in COPD (mean +/- SD SRI
      summary score (SRI-SS) 52.5 +/- 15.6) than non-COPD patients (67.6 +/- 16.4; p <
      0.001). Overall mortality during 28.9 +/- 8.8 months of follow-up was 19.1%
      (31.6% in COPD, 9.8% in non-COPD). To identify the overall role of SRI, we first
      evaluated the total study population. SRI-SS and its subdomains (except
      attendance symptoms and sleep), as well as body mass index (BMI), leukocyte
      number and spirometric indices were associated with long-term survival (p < 0.01
      each). Of these, SRI-SS, leukocytes and forced expiratory volume in 1 s (FEV1)
      turned out to be independent predictors (p < 0.05 each). More specifically, in
      non-COPD patients SRI-SS and most of its subdomains, as well as leukocyte number,
      were related to survival (p < 0.05), whereas in patients with COPD only BMI and
      lung function but not SRI were predictive. CONCLUSION: In patients with CHRF and
      HMV, the disease-specific SRI was an overall predictor of long-term survival in
      addition to established risk factors. However, the SRI predominantly beared
      information regarding long-term survival in non-COPD patients, while in COPD
      patients objective measures of the disease state were superior. This on one hand
      highlights the significance of HRQL in the long-term course of patients with
      CHRF, on the other hand it suggests that the predictive value of HRQL depends on
      the underlying disease.

PMID- 18086312
TI  - The impact of a reduced dose of dexamethasone on glucose control after coronary
      artery bypass surgery.
AB  - BACKGROUND: Intensive insulin therapy to maintain normoglycemia after cardiac
      surgery reduces morbidity and mortality. We investigated the magnitude and
      duration of hyperglycemia caused by dexamethasone administered after
      cardiopulmonary bypass. METHODS: A single-center before-after cohort study was
      performed. All consecutive patients undergoing coronary artery bypass grafting
      with cardiopulmonary bypass during a 6-month period were included. Insulin
      administration was guided by a sliding scale protocol. Halfway the observation
      period, the dexamethasone protocol was changed. The single dose (1D) group
      received a pre-operative dose of dexamethasone of 1 mg/kg. The double dose group
      (2D) received an additional dose of 0.5 mg/kg of dexamethasone post-operatively
      at ICU admission. RESULTS: We included 116 patients in the 1D group and 158
      patients in the 2D group. There were no significant baseline differences between
      the groups. Median Euroscore was 5. In univariable analysis, the glucose level
      was different between groups 1D and 2D at 4, 6, 9, 12 and 24 hours after ICU
      admission (all p < 0.001). Insulin infusion was higher in the 1D group. Corrected
      for insulin dose in multivariable linear analysis, the difference in glucose
      between the 1D and 2D groups was 1.5 mmol/L (95% confidence interval 1.0-2.0, p <
      0.001) 12 hours after ICU admission. CONCLUSION: Dexamethasone exerts a
      hyperglycemic effect in cardiac surgery patients. Patients receiving high-dose
      corticosteroid therapy should be monitored and treated more intensively for
      hyperglycemic episodes.

PMID- 18086311
TI  - Implementing academic detailing for breast cancer screening in underserved
      communities.
AB  - BACKGROUND: African American and Hispanic women, such as those living in the
      northern Manhattan and the South Bronx neighborhoods of New York City, are
      generally underserved with regard to breast cancer prevention and screening
      practices, even though they are more likely to die of breast cancer than are
      other women. Primary care physicians (PCPs) are critical for the recommendation
      of breast cancer screening to their patients. Academic detailing is a promising
      strategy for improving PCP performance in recommending breast cancer screening,
      yet little is known about the effects of academic detailing on breast cancer
      screening among physicians who practice in medically underserved areas. We
      assessed the effectiveness of an enhanced, multi-component academic detailing
      intervention in increasing recommendations for breast cancer screening within a
      sample of community-based urban physicians. METHODS: Two medically underserved
      communities were matched and randomized to intervention and control arms. Ninety
      four primary care community (i.e., not hospital based) physicians in northern
      Manhattan were compared to 74 physicians in the South Bronx neighborhoods of the
      New York City metropolitan area. Intervention participants received enhanced
      physician-directed academic detailing, using the American Cancer Society
      guidelines for the early detection of breast cancer. Control group physicians
      received no intervention. We conducted interviews to measure primary care
      physicians' self-reported recommendation of mammography and Clinical Breast
      Examination (CBE), and whether PCPs taught women how to perform breast self
      examination (BSE). RESULTS: Using multivariate analyses, we found a statistically
      significant intervention effect on the recommendation of CBE to women patients
      age 40 and over; mammography and breast self examination reports increased across
      both arms from baseline to follow-up, according to physician self-report. At post
      test, physician involvement in additional educational programs, enhanced self
      efficacy in counseling for prevention, the routine use of chart reminders,
      computer- rather than paper-based prompting and tracking approaches, printed
      patient education materials, performance targets for mammography, and increased
      involvement of nursing and other office staff were associated with increased
      screening. CONCLUSION: We found some evidence of improvement in breast cancer
      screening practices due to enhanced academic detailing among primary care
      physicians practicing in urban underserved communities.

PMID- 18086314
TI  - Enhanced balance associated with coordination training with stochastic resonance
      stimulation in subjects with functional ankle instability: an experimental trial.
AB  - BACKGROUND: Ankle sprains are common injuries that often lead to functional ankle
      instability (FAI), which is a pathology defined by sensations of instability at
      the ankle and recurrent ankle sprain injury. Poor postural stability has been
      associated with FAI, and sports medicine clinicians rehabilitate balance deficits
      to prevent ankle sprains. Subsensory electrical noise known as stochastic
      resonance (SR) stimulation has been used in conjunction with coordination
      training to improve dynamic postural instabilities associated with FAI. However,
      unlike static postural deficits, dynamic impairments have not been indicative of
      ankle sprain injury. Therefore, the purpose of this study was to examine the
      effects of coordination training with or without SR stimulation on static
      postural stability. Improving postural instabilities associated with FAI has
      implications for increasing ankle joint stability and decreasing recurrent ankle
      sprains. METHODS: This study was conducted in a research laboratory. Thirty
      subjects with FAI were randomly assigned to either a: 1) conventional
      coordination training group (CCT); 2) SR stimulation coordination training group
      (SCT); or 3) control group. Training groups performed coordination exercises for
      six weeks. The SCT group received SR stimulation during training, while the CCT
      group only performed coordination training. Single leg postural stability was
      measured after the completion of balance training. Static postural stability was
      quantified on a force plate using anterior/posterior (A/P) and medial/lateral
      (M/L) center-of-pressure velocity (COPvel), M/L COP standard deviation (COPsd),
      M/L COP maximum excursion (COPmax), and COP area (COParea). RESULTS: Treatment
      effects comparing posttest to pretest COP measures were highest for the SCT
      group. At posttest, the SCT group had reduced A/P COPvel (2.3 +/- 0.4 cm/s vs.
      2.7 +/- 0.6 cm/s), M/L COPvel (2.6 +/- 0.5 cm/s vs. 2.9 +/- 0.5 cm/s), M/L COPsd
      (0.63 +/- 0.12 cm vs. 0.73 +/- 0.11 cm), M/L COPmax (1.76 +/- 0.25 cm vs. 1.98 +/
      0.25 cm), and COParea (0.13 +/- 0.03 cm2 vs. 0.16 +/- 0.04 cm2) than the pooled
      means of the CCT and control groups (P < 0.05). CONCLUSION: Reduced values in COP
      measures indicated postural stability improvements. Thus, six weeks of
      coordination training with SR stimulation enhanced postural stability. Future
      research should examine the use of SR stimulation for decreasing recurrent ankle
      sprain injury in physically active individuals with FAI.

PMID- 18086315
TI  - Anatomically based lower limb nerve model for electrical stimulation.
AB  - BACKGROUND: Functional Electrical Stimulation (FES) is a technique that aims to
      rehabilitate or restore functionality of skeletal muscles using external
      electrical stimulation. Despite the success achieved within the field of FES,
      there are still a number of questions that remain unanswered. One way of
      providing input to the answers is through the use of computational models.
      METHODS: This paper describes the development of an anatomically based computer
      model of the motor neurons in the lower limb of the human leg and shows how it
      can be used to simulate electrical signal propagation from the beginning of the
      sciatic nerve to a skeletal muscle. One-dimensional cubic Hermite finite elements
      were used to represent the major portions of the lower limb nerves. These
      elements were fit to data that had been digitised using images from the Visible
      Man project. Nerves smaller than approximately 1 mm could not be seen in the
      images, and thus a tree-branching algorithm was used to connect the ends of the
      fitted nerve model to the respective skeletal muscle. To simulate electrical
      propagation, a previously published mammalian nerve model was implemented and
      solved on the anatomically based nerve mesh using a finite difference method. The
      grid points for the finite difference method were derived from the fitted finite
      element mesh. By adjusting the tree-branching algorithm, it is possible to
      represent different levels of motor-unit recruitment. RESULTS: To illustrate the
      process of a propagating nerve stimulus to a muscle in detail, the above method
      was applied to the nerve tree that connects to the human semitendinosus muscle. A
      conduction velocity of 89.8 m/s was obtained for a 15 mum diameter nerve fibre.
      This signal was successfully propagated down the motor neurons to a selected
      group of motor units in the muscle. CONCLUSION: An anatomically and
      physiologically based model of the posterior motor neurons in the human lower
      limb was developed. This model can be used to examine the effect of external
      stimulation on nerve and muscle activity, as may occur, for example, in the field
      of FES.

PMID- 18086313
TI  - A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological
      inhibition.
AB  - Mechanical hyperalgesia is a clinically-relevant form of pain sensitization that
      develops through largely unknown mechanisms. TRPA1, a Transient Receptor
      Potential ion channel, is a sensor of pungent chemicals that may play a role in
      acute noxious mechanosensation and cold thermosensation. We have developed a
      specific small molecule TRPA1 inhibitor (AP18) that can reduce cinnameldehyde
      induced nociception in vivo. Interestingly, AP18 is capable of reversing CFA
      induced mechanical hyperalgesia in mice. Although TRPA1-deficient mice develop
      normal CFA-induced hyperalgeisa, AP18 is ineffective in the knockout mice,
      consistent with an on-target mechanism. Therefore, TRPA1 plays a role in
      sensitization of nociception, and that compensation in TRPA1-deficient mice masks
      this requirement.

PMID- 18086316
TI  - Does any aspect of mind survive brain damage that typically leads to a persistent
      vegetative state? Ethical considerations.
AB  - Recent neuroscientific evidence brings into question the conclusion that all
      aspects of consciousness are gone in patients who have descended into a
      persistent vegetative state (PVS). Here we summarize the evidence from human
      brain imaging as well as neurological damage in animals and humans suggesting
      that some form of consciousness can survive brain damage that commonly causes
      PVS. We also raise the issue that neuroscientific evidence indicates that raw
      emotional feelings (primary-process affects) can exist without any cognitive
      awareness of those feelings. Likewise, the basic brain mechanisms for thirst and
      hunger exist in brain regions typically not damaged by PVS. If affective feelings
      can exist without cognitive awareness of those feelings, then it is possible that
      the instinctual emotional actions and pain "reflexes" often exhibited by PVS
      patients may indicate some level of mentality remaining in PVS patients. Indeed,
      it is possible such raw affective feelings are intensified when PVS patients are
      removed from life-supports. They may still experience a variety of primary
      process affective states that could constitute forms of suffering. If so,
      withdrawal of life-support may violate the principle of nonmaleficence and be
      tantamount to inflicting inadvertent "cruel and unusual punishment" on patients
      whose potential distress, during the process of dying, needs to be considered in
      ethical decision-making about how such individuals should be treated, especially
      when their lives are ended by termination of life-supports. Medical wisdom may
      dictate the use of more rapid pharmacological forms of euthanasia that minimize
      distress than the de facto euthanasia of life-support termination that may lead
      to excruciating feelings of pure thirst and other negative affective feelings in
      the absence of any reflective awareness.

PMID- 18086317
TI  - Nose thyself: individuality in the human olfactory genome.
AB  - A recent study using cell-based assays together with an olfactory psychophysical
      survey in humans has established a link between a genetic polymorphism in an
      odorant receptor and variability in perception of the smell of the steroid
      androstenone.

PMID- 18086318
TI  - A wise nurse can manage a paper protocol but prefers intelligent technology.

PMID- 18086319
TI  - Does serum procalcitonin have a diagnostic value in febrile adult patients
      presenting to the emergency department?

PMID- 18086320
TI  - Toll-like receptors and innate immune responses in systemic lupus erythematosus.
AB  - A series of discoveries over the past several years has provided a new paradigm
      for understanding autoimmunity in systemic lupus erythematosus. The discoveries
      of pattern recognition receptors and of how these receptors can be recruited into
      autoimmune responses underpin this paradigm. The implications of these
      observations continue to unfold with ongoing investigation into the range and
      specificity of pattern recognition receptors, into how immune complexes
      containing nucleic acids trigger these receptors, into how endogenous
      macromolecular 'danger signals' stimulate innate immune responses, and into the
      effect of pattern recognition receptor activation on various cell types in
      initiating and perpetuating autoimmunity. The development of clinical trials
      using therapeutic agents that target components of the innate immune system
      suggests that these advances may soon culminate in new medications for treating
      patients with systemic lupus erythematosus.

PMID- 18086321
TI  - What if Watson had said "Apes evolved from man"?

PMID- 18086322
TI  - Bench-to-bedside review: leadership and conflict management in the intensive care
      unit.
AB  - In the management of critical care units, leadership and conflict management are
      vital areas for the successful performance of the unit. In this article a
      practical approach to define competencies for leadership and principles and
      practices of conflict management are offered. This article is, by lack of
      relevant intensive care unit (ICU) literature, not evidence based, but it is the
      result of personal experience and a study of literature on leadership as well on
      conflicts and negotiations in non-medical areas. From this, information was
      selected that was recognisable to the authors and, thus, also seems to be useful
      knowledge for medical doctors in the ICU environment.

PMID- 18086323
TI  - The impact of critical care outreach: is there one?
AB  - An evaluation of critical care outreach services was published in the previous
      issue of Critical Care that fails to demonstrate any important outcome benefit
      associated with these services. It is now time to ask some difficult questions
      about the future of outreach, including whether the lack of evidence should lead
      to disinvestment in such services.

PMID- 18086324
TI  - Osteoactivin/HGFIN: is it a tumor suppressor or mediator of metastasis in breast
      cancer?

PMID- 18086325
TI  - The protective side of progesterone.

PMID- 18086326
TI  - The ins and outs of translation.

PMID- 18086327
TI  - Is interleukin-1 a good target for therapeutic intervention in intervertebral
      disc degeneration: lessons from the osteoarthritic experience.
AB  - IL-1 plays a key role in disc degeneration and could be a valid target for
      inhibiting this process. IL-1 receptor antagonist (IL-1ra) might be a good
      candidate to inhibit IL-1 activity. However, many questions need to be addressed
      before contemplating therapy in humans. IL-1 blockade is also a great challenge
      in osteoarthritis and results from animal models suggest that IL-1ra may have
      beneficial effects. The clinical benefit of a local injection of IL-1ra in knee
      osteoarthritis may be limited by the antagonist's short half-life. Further
      studies with longer-lasting antagonists are needed to explore this new
      therapeutic approach.

PMID- 18086328
TI  - Steroid treatment for persistent ARDS: a word of caution.

PMID- 18086329
TI  - Positive end-expiratory pressure in acute respiratory distress syndrome: should
      the 'open lung strategy' be replaced by a 'protective lung strategy'?
AB  - In patients with acute respiratory distress syndrome, positive end-expiratory
      pressure is associated with alveolar recruitment and lung hyperinflation despite
      the administration of a low tidal volume. The best positive end-expiratory
      pressure should correspond to the best compromise between recruitment and
      distension, a condition that coincides with the best respiratory elastance.

PMID- 18086330
TI  - Tissue Doppler in critical illness.

PMID- 18086332
TI  - Higher calcium urinary loss induced by a calcium sulphate-rich mineral water
      intake than by milk in young women: comments by Arnaud.

PMID- 18086331
TI  - Nutrition and bone health projects funded by the UK Food Standards Agency: have
      they helped to inform public health policy?
AB  - The UK Food Standards Agency convened an international group of expert scientists
      to review the Agency-funded projects on diet and bone health in the context of
      developments in the field as a whole. The potential benefits of fruit and
      vegetables, vitamin K, early-life nutrition and vitamin D on bone health were
      presented and reviewed. The workshop reached two conclusions which have public
      health implications. First, that promoting a diet rich in fruit and vegetable
      intakes might be beneficial to bone health and would be very unlikely to produce
      adverse consequences on bone health. The mechanism(s) for any effect of fruit and
      vegetables remains unknown, but the results from these projects did not support
      the postulated acid-base balance hypothesis. Secondly, increased dietary
      consumption of vitamin K may contribute to bone health, possibly through its
      ability to increase the gamma-carboxylation status of bone proteins such as
      osteocalcin. A supplementation trial comparing vitamin K supplementation with Ca
      and vitamin D showed an additional effect of vitamin K against baseline levels of
      bone mineral density, but the benefit was only seen at one bone site. The major
      research gap identified was the need to investigate vitamin D status to define
      deficiency, insufficiency and depletion across age and ethnic groups in relation
      to bone health.

PMID- 18086333
TI  - Effects of low- and high-volume resistance exercise on postprandial lipaemia:
      comments by Burns and Stensel.

PMID- 18086334
TI  - Foregut duplication cyst of the pharynx.
AB  - INTRODUCTION: Foregut duplication cysts are heterotrophic rests of foregut
      derived epithelium which are usually found in the abdomen and thorax; rarely are
      they found in the head and neck. CASE REPORT: We describe the case of a
      pharyngeal foregut duplication cyst presenting with airway obstruction in a
      neonate. We also review the pathology, investigation and management of this rare
      condition. DISCUSSION: The occurrence of a foregut duplication cyst in the head
      and neck region mandates vigilance with respect to the airway. Magnetic resonance
      imaging is a useful part of pre-operative evaluation but cannot be relied upon
      for definitive diagnosis. Although foregut duplication cysts are benign lesions,
      definitive cure ultimately requires surgical excision, and this is often the
      means by which a definitive diagnosis is made. The prognosis for these lesions is
      excellent, with no reports in the literature of recurrence following excision.

PMID- 18086335
TI  - Endoscopic 'cold steel' versus laser dacryocystorhinostomy: completing the audit
      cycle.
AB  - INTRODUCTION: Dacryocystorhinostomy via an endonasal route has been adopted in
      our department. This audit study describes and compares our results for external,
      laser endonasal and 'cold steel' endonasal techniques. Success was defined as a
      subjective report of eye watering being 'better' or 'cured'. Data were obtained
      from a retrospective review of the medical records of all patients undergoing
      primary dacryocystorhinostomy in our department. 'Gold standard': External
      dacryocystorhinostomy performed by a consultant ophthalmologist was taken as our
      gold standard. In our study, the success rate for external dacryocystorhinostomy
      was 94 per cent. First cycle - laser-assisted endonasal dacryocystorhinostomy:
      Our initial results for endonasal laser-assisted dacryocystorhinostomy produced a
      success rate of 64 per cent, which was significantly worse than that for external
      dacryocystorhinostomy. These results have been previously published. CHANGE IN
      PRACTICE: Evidence suggested that cold steel endonasal dacryocystorhinostomy was
      more effective, and we adopted this as our technique of choice. Second cycle -
      cold steel endonasal dacryocystorhinostomy: Over a four-year period, 57 cases
      completed a full nine months' follow up. 93 per cent were completed as day cases
      and 39 per cent were performed under local anaesthetic. The success rate was 79
      per cent (45/57). There was no difference in success rates when this procedure
      was compared with external dacryocystorhinostomy (p = 0.55). The type of
      anaesthetic used (i.e. local vs general) made no difference to the success rate
      (p = 0.93). CHANGE IN PRACTICE: Cold steel endonasal dacryocystorhinostomy was as
      effective as the gold standard, i.e. external dacryocystorhinostomy. Laser
      assisted dacryocystorhinostomy was significantly less successful than external
      dacryocystorhinostomy. Due to the benefits of decreased operating time, lower
      morbidity and success under local anaesthetic, we recommend cold steel endonasal
      dacryocystorhinostomy as our procedure of choice for the treatment of epiphora.

PMID- 18086336
TI  - Inner-ear obliteration in ulcerative colitis patients with sensorineural hearing
      loss.
AB  - OBJECTIVE: Systemic autoimmune diseases, including ulcerative colitis, may
      involve the inner ear. Several ulcerative colitis cases presenting with
      sensorineural hearing loss have been reported. We report the T2-weighted, three
      dimensional, inner-ear magnetic resonance imaging findings in the inner ears of
      two such patients. METHODS: Case reports and a review of the literature
      concerning autoimmune disease and sensorineural hearing loss are presented.
      RESULTS: We describe two cases of ulcerative colitis with sensorineural hearing
      loss in which three-dimensional magnetic resonance imaging revealed obliteration
      of the inner ear. Those inner ears with obliteration had severe hearing loss, and
      responded poorly to steroid therapy. CONCLUSION: To our knowledge, there has been
      no previous published report of the T2-weighted, inner-ear magnetic resonance
      imaging findings of cases of ulcerative colitis with sensorineural hearing loss.
      This paper represents the first published report in the world literature of inner
      ear obliteration in such patients. Three-dimensional magnetic resonance imaging
      is beneficial in elucidating the pathophysiology of the inner-ear involvement
      seen in ulcerative colitis.

PMID- 18086337
TI  - Proximity seeking in adult attachment: examining the role of automatic approach
      avoidance tendencies.
AB  - In two experiments, participants made symbolic approach and avoidance movements
      towards or away from attachment figure- and acquaintance-related cues after being
      primed with a distressing or a non-distressing context. Results showed that
      automatic approach responses towards the attachment figure were stronger in a
      distressing than in a non-distressing context, regardless of whether the source
      of distress was attachment-relevant or -irrelevant and regardless of one's
      attachment style. Individual differences in attachment anxiety and avoidance were
      associated with the predicted patterns of approach-avoidance tendencies:
      attachment anxiety heightened the tendency to approach the attachment Figure
      (Experiments 1 and 2), whereas attachment avoidance reduced this tendency
      (Experiment 2). Findings are discussed as providing first evidence on the role of
      automatic action tendencies in adult attachment.

PMID- 18086339
TI  - The influence of context-specific and dispositional achievement goals on
      children's paired collaborative interaction.
AB  - BACKGROUND: Research has demonstrated that working collaboratively can have
      positive effects on children's learning. While key factors have been identified
      which influence the quality of these interactions, little research has addressed
      the influence of children's achievement goals on collaborative behaviour. AIMS:
      This paper investigates the influence of mastery and performance goals on the
      nature of children's collaborative participation while playing a problem-solving
      computer game with a peer. SAMPLE: Forty-eight primary schoolchildren aged 8-10
      years were divided into two groups: those displaying strong personal goal
      preferences (dispositional group: N=14) and those whose goal preferences were
      context-dependent, displaying no consistent bias for either mastery or
      performance goals (context-dependent: N=34). Children were paired on the basis of
      same gender, year group, and goal orientation. METHOD: Context-dependent pairs
      were assigned to either a mastery or a performance condition in which they
      received goal-focused instructions. Dispositional pairs received only the
      instructions to collaborate given to all groups. Collaborative sessions were
      videotaped and interactions coded. RESULTS: Children who were assigned mastery
      goals engaged in significantly more elaborated problem-solving discussion whilst
      children who were assigned performance goals engaged in more executive help
      seeking and displayed lower levels of metacognitive control. Dispositional pairs
      shared some similar patterns, according to goal orientation, as context-dependent
      pairs. CONCLUSIONS: Goal-focused instructions can be used to influence the nature
      and quality of children's paired interactions. Instructing children towards
      mastery goals appears to promote a more collaborative style of interaction.

PMID- 18086338
TI  - Bootstrap confidence intervals in multi-level simultaneous component analysis.
AB  - Multi-level simultaneous component analysis (MLSCA) was designed for the
      exploratory analysis of hierarchically ordered data. MLSCA specifies a component
      model for each level in the data, where appropriate constraints express possible
      similarities between groups of objects at a certain level, yielding four MLSCA
      variants. The present paper discusses different bootstrap strategies for
      estimating confidence intervals (CIs) on the individual parameters. In selecting
      a proper strategy, the main issues to address are the resampling scheme and the
      non-uniqueness of the parameters. The resampling scheme depends on which level(s)
      in the hierarchy are considered random, and which fixed. The degree of non
      uniqueness depends on the MLSCA variant, and, in two variants, the extent to
      which the user exploits the transformational freedom. A comparative simulation
      study examines the quality of bootstrap CIs of different MLSCA parameters.
      Generally, the quality of bootstrap CIs appears to be good, provided the sample
      sizes are sufficient at each level that is considered to be random. The latter
      implies that if more than a single level is considered random, the total number
      of observations necessary to obtain reliable inferential information increases
      dramatically. An empirical example illustrates the use of bootstrap CIs in MLSCA.

PMID- 18086340
TI  - Informed consent and psychotherapy: an interpretative phenomenological analysis
      of therapists' views.
AB  - OBJECTIVES: To examine the issue of informed consent and how this is translated
      into clinical psychotherapy practice. DESIGN: A qualitative approach was taken in
      which interviews were used to produce data. METHODS: Nine clinical psychologists
      with specialist psychodynamic training took part in the research. Participants
      were interviewed using a semi-structured interview schedule. The interviews were
      transcribed and the data were analysed using interpretative phenomenological
      analysis. RESULTS: The tensions between balancing the requirements of informed
      consent with psychodynamic practice were explored and the notion of whether
      clients can truly be informed prior to undertaking psychodynamic therapy was
      raised. Four major themes emerged from the data: 'psychodynamic therapy as
      risky'; 'balancing expectations between therapist and client'; 'psychodynamic
      therapy as unique and experiential'; and 'informed consent as complex: a
      linguistic conceit'? CONCLUSIONS: This research has been valuable in identifying
      therapists' views and experiences of how the issue of informed consent is
      addressed in therapeutic practice. In the light of the findings of this research,
      future investigation would benefit from more detailed examination of the process
      of providing informed consent, examining whether, and how often, consent issues
      are revisited by therapists. More research focusing on the views and need of
      clients are also warranted.

PMID- 18086341
TI  - Purine Nucleosidase Phosphorylase (PNP): A novel target in leukemias and
      lymphomas.

PMID- 18086342
TI  - Three new drugs for acute lymphoblastic leukemia: nelarabine, clofarabine, and
      forodesine.
AB  - The search for more effective and safer anti-leukemia therapies has led to the
      identification of several new agents that show activity against specific types of
      acute lymphoblastic leukemia (ALL). Recently, three novel purine nucleoside
      analogues (nelarabine, clofarabine, and forodesine) have shown promising activity
      in patients with relapsed or refractory ALL. Of these, nelarabine has shown
      clinically meaningful benefit in patients with T-cell ALL, with overall response
      rates ranging from 33% to 60%, the induction of durable complete remissions, and
      an overall 1-year survival rate of 28% in adults. Clofarabine has also shown
      promising clinical activity in pediatric patients, with an overall response rate
      of 30%, and some patients are able to proceed to allogeneic hematopoietic cell
      transplantation. Forodesine is the most recent novel agent, with a unique
      mechanism that has shown single-agent activity in relapsed and refractory T- and
      B-cell leukemias and cutaneous lymphomas. Although clinical experience is
      limited, treatment-related toxicities appear to be mild. The rationale,
      pharmacology, and clinical experience to date with these agents in the treatment
      of patients with refractory acute leukemia are reviewed, with a highlight on ALL.

PMID- 18086343
TI  - Mycosis fungoides: pathophysiology and emerging therapies.
AB  - Primary cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of non
      Hodgkin's lymphomas characterized by skin infiltration of neoplastic T
      lymphocytes. Mycosis fungoides and its leukemic variant Sezary syndrome represent
      the most common CTCL subtypes. Current treatment for patients with mycosis
      fungoides involves topical and systemic therapies for the cutaneous
      manifestations. However, no therapy is curative and patients often progress to
      advanced extracutaneous CTCL with visceral organ complications or relapsed
      disease that is frequently refractory to most topical and aggressive systemic
      regimens. The emergence of novel targeted therapies such as biologic agents,
      histone deacetylase inhibitors, and purine nucleoside phosphorylase inhibitors
      offers promise for more effective and safer treatment strategies for refractory
      CTCLs.

PMID- 18086344
TI  - Purine nucleoside phosphorylase inhibition as a novel therapeutic approach for B
      cell lymphoid malignancies.
AB  - Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of
      ribonucleosides and 2'-deoxyribonucleosides to their respective bases. Endogenous
      PNP deficiency leads to specific T-cell immunodeficiency, a genetic disease that
      has prompted the development of PNP inhibitors as potential therapies for T-cell
      mediated diseases. PNP inhibition leads to the elevation of 2'-deoxyguanosine
      levels and accumulation of intracellular deoxyguanosine 5'-triphosphate, inducing
      cellular apoptosis. Forodesine is a highly potent, orally active, rationally
      designed PNP inhibitor that has shown activity in preclinical studies with
      malignant cells and clinical utility against T-cell acute lymphoblastic leukemia
      and cutaneous T-cell lymphoma. Additional preliminary findings support its use
      for the management of some B-cell malignancies.

PMID- 18086345
TI  - Clinical management of T-cell malignancies: current perspectives, key issues, and
      emerging therapies.
AB  - Peripheral T-cell non-Hodgkin's lymphomas are a diverse group of disorders, most
      of which carry a poor prognosis. Relapse is common following the administration
      of most currently available agents, and there are few effective options for
      salvage therapy. This article discusses a number of novel emerging therapies for
      the treatment of patients with T-cell non-Hodgkin's lymphomas, including the
      antimetabolite nelarabine, the purine nucleoside phosphorylase inhibitor
      forodesine, the pyrimidine analogue gemcitabine, and the fusion protein
      denileukin diftitox. Other therapies discussed for the treatment of patients with
      T-cell non-Hodgkin's lymphomas include bendamustine, gallium nitrate, and
      bortezomib, as well as the mammalian target of rapamycin inhibitors, small
      molecules that target the apoptotic pathways, immunomodulatory agents, and
      monoclonal antibodies.

PMID- 18086346
TI  - Forodesine treatment and post-transplant graft-versus-host disease in two
      patients with acute leukemia: facilitation of graft-versus-leukemia effect?
AB  - This article presents two case studies of patients diagnosed with T-cell acute
      lymphoblastic leukemia who relapsed following allogeneic hematopoietic stem cell
      transplantation and were subsequently enrolled in a clinical trial in which they
      received forodesine hydrochloride, a rationally designed, potent, transition
      state inhibitor of purine nucleoside phosphorylase. Forodesine induced complete
      remission in both patients. Graft-versus-host disease developed subsequently but
      was treated successfully with conventional immunosuppressive therapy. Both
      patients remain in complete remission at the most recent follow-up. We
      hypothesize that forodesine contributed to a primary anti-leukemic cytotoxic
      effect as well as a secondary immunologic effect by allowing the development of
      an ongoing graft-versus-leukemia effect in these patients.

PMID- 18086354
TI  - Abstracts of the 4th Symposium on Lysosomal Storage Disorders. Vienna, Austria.
      March 29-31, 2007.

PMID- 18086347
TI  - Pharmacology and mechanism of action of forodesine, a T-cell targeted agent.
AB  - Purine nucleoside phosphorylase (PNP) was recognized more than 30 years ago as a
      potential target for the treatment of patients with T-cell malignancies when an
      inherited deficiency of PNP was reported to be associated with a profound T-cell
      lymphopenia. The biochemical basis for this T-cell deficiency was subsequently
      shown to be related to the accumulation of plasma 2'-deoxyguanosine (dGuo) and
      intracellular dGuo triphosphate (dGTP). These observations have led to a search
      for PNP inhibitors that would be useful clinically in the management of T cell
      derived malignancies. The most potent inhibitor of PNP described to date is
      forodesine, a rationally designed, transition-state analogue inhibitor. The
      preclinical and clinical pharmacology of forodesine showed its effectiveness in
      inhibiting PNP and augmenting dGuo levels in plasma. Increased dGTP
      concentrations in leukemia cells of different lineages provides strong support
      for the potential use of this agent in the treatment of patients with hematologic
      malignancies of both T- and B-cell origin.

PMID- 18086369
TI  - Macrophage and dendritic cells. Editorial.

PMID- 18086370
TI  - Binding of human papilloma virus L1 virus-like particles to dendritic cells is
      mediated through heparan sulfates and induces immune activation.
AB  - Immunization using human papilloma virus (HPV)-L1 virus-like particles (VLPs)
      induces a robust and effective immune response, which has recently resulted in
      the implementation of the HPV-L1 VLP vaccination in health programs. However,
      during infection, HPV can escape immune surveillance leading to latency and
      disease. Dendritic cells (DCs) induce effective immune responses after
      vaccination, but might also induce immune modulation during infection. The
      interaction of HPV-L1 VLPs with mucosal DCs determines the immune response.
      However, little is known about the receptors on mucosal DC subsets involved in
      HPV-L1 VLP binding. Therefore, we set out to investigate the interaction of HPV
      L1 VLPs with the different mucosal DC subsets; the subepithelial DCs and
      Langerhans cells (LCs). We observed strong binding of HPV-L1 VLPs to both DCs and
      LCs. We did not observe an involvement for C-type lectins such as dendritic cell
      specific ICAM-3 grabbing non-integrin (DC-SIGN) and langerin. The HPV-L1 VLP
      binding to DCs was mediated through heparan sulfates, since it was abrogated by
      heparinase-II treatment. The heparan sulfate proteoglycan syndecan-3 binds VLPs
      and is expressed on both DCs and LCs. Binding of VLPs to DCs, but not to LCs,
      strongly correlated with the levels of heparan sulfates and syndecan-3,
      suggesting that syndecan-3 is the main receptor for HPV-L1 VLPs on DCs. VLP
      interaction with DCs resulted in the up-regulation of co-stimulatory molecules
      and the production of the cytokines IL-6, IL-8, IL-10 and IL-12p40. Our results
      support an important role for syndecan-3 as a HPV receptor on DCs, which could be
      important for both vaccine development and understanding HPV pathogenesis.

PMID- 18086371
TI  - Responsiveness of fibrocytes to toll-like receptor danger signals.
AB  - Circulating myeloid cells such as plasmacytoid dendritic cells (pDC), blood DC
      and monocytes act as blood sentinels detecting invading pathogens through a large
      repertoire of expression of toll-like receptors (TLRs). Activation of these
      receptors is crucial to detect invading pathogens by the innate immune system. In
      the present work, we analysed the TLR responsiveness of fibrocytes, a blood
      derived cell type of myeloid origin. Fibrocytes efficiently responded to TLR2,
      TLR4, and TLR7 ligands as well as to poly (I:C) or viral stimulation by producing
      high amount of interleukin-6. Upon virus infection of fibrocytes, IFN type I was
      also induced. When compared to pDC or Flt3 ligand-derived DC, fibrocytes produced
      5 times and 60 times more IL-6, respectively. This response was associated with a
      rapid and efficient translocation of the NF-kappaB transcription factor. Analysis
      of the expression and functionality of TLR7 in peripheral blood leukocyte
      subpopulations suggested that this receptor is expressed and functional in a
      CD163(+) monocytic cell subpopulation containing the fibrocyte precursors.
      Considering the rapid entry of fibrocytes into wounds, this efficient
      responsiveness to TLR danger signals, reflects a potentially important role of
      these cells in the first line of defence against pathogen invasion following
      traumata.

PMID- 18086372
TI  - The role of viral nucleic acid recognition in dendritic cells for innate and
      adaptive antiviral immunity.
AB  - Dendritic cells which are located at the interface of innate and adaptive
      immunity are targets for infection by many different DNA and RNA viruses.
      Dendritic cell subpopulations express specific nucleic acid recognition receptors
      belonging to the Toll-like receptor family (TLR3, 7, 8, 9) and the cytosolic RNA
      helicase family (RIG-I, MDA5, LGP2). Activation of dendritic cells by viral DNA
      and RNA via these receptors is essential for triggering the innate antiviral
      immune response and shaping the ensuing adaptive antiviral immunity. This review
      will summarize our current knowledge of viral nucleic acid recognition and
      signaling by Toll-like receptors and RNA helicases focusing on recent evidence
      for their specific functions in antiviral defense in vivo.

PMID- 18086373
TI  - Role of Toll-like receptor responses for sepsis pathogenesis.
AB  - Sepsis remains a serious clinical problem because of high patient morbidity and
      mortality. Despite significant advances in critical care, there is still no
      efficient causal therapy applicable to patients indicating the need to further
      elucidate the molecular pathways leading to the immunopathology of sepsis. The
      importance of Toll-like receptors (TLR) for the induction of immune responses
      against sepsis was demonstrated in humans exhibiting polymorphisms in TLR genes
      and in animal models using genetically modified mouse strains. Because of the
      clinical heterogeneity in human sepsis and the complex pathomechanisms underlying
      sepsis, several different animal models might be used to cover the diverse
      features of sepsis. TLR receptors induce signaling through the adapter proteins
      MyD88 and TRIF. TLR signaling is tightly controlled at different steps of the
      signaling cascade by series of regulatory proteins. Using a model of severe
      polymicrobial septic peritonitis we could show that single TLRs are dispensable
      for the induction of innate immune responses under those conditions. However,
      genetic ablation of MyD88 or TRIF/type-I interferon signaling pathways prevented
      hyper-inflammation and attenuated the pathogenic consequences of sepsis
      indicating that dampening common signaling pathways may create a moderate signal
      strength which is associated with favorable immune responses. Therefore, broad
      knowledge about the regulation of TLR-induced signaling pathways may further
      elucidate the immune mechanisms during sepsis and targeting of TLR adapter
      molecules may provide a new therapeutic strategy against severe sepsis.

PMID- 18086374
TI  - A genome-wide analysis of LPS tolerance in macrophages.
AB  - Among the multiple mechanisms that control the intensity and duration of
      macrophage activation, the development of a state of refractoriness to a second
      stimulation in cells treated with lipopolysaccharide (LPS) has long been
      recognized. Release of inhibitory cytokines and alterations in intracellular
      signaling pathways may be involved in the development of LPS tolerance. Although
      a number of molecules have been implicated, a detailed picture of the molecular
      changes in LPS tolerance is still missing. We have used a genome-wide gene
      expression analysis approach to (i) define which fraction of LPS target genes are
      subject to tolerance induction and (ii) identify genes that are expressed at high
      levels in tolerant macrophages. Our data show that in LPS-tolerant macrophages
      the vast majority of LPS-induced gene expression is abrogated. The extent of
      tolerance induction varies for individual genes, and a small subset of genes
      appears to be exempted. Compared to other negative control mechanisms of
      macrophages, e.g., IL-10-induced deactivation, LPS tolerance inhibits a much
      wider range of transcriptional targets. Some previously described negative
      regulators of TLR signaling (e.g. IRAK-M) were confirmed as expressed at higher
      levels in LPS-tolerant macrophages. In addition, we discuss other potential
      players in LPS tolerance identified in this group of genes.

PMID- 18086375
TI  - Production of IL-12, IL-23 and IL-27p28 by bone marrow-derived conventional
      dendritic cells rather than macrophages after LPS/TLR4-dependent induction by
      Salmonella Enteritidis.
AB  - Induction of the interleukin-12 (IL-12) cytokine family comprising IL-12, IL-23,
      IL-27, and IL-12p40 by intracellular pathogens is required for orchestration of
      cell-mediated immune responses. Macrophages (MPhi) have been shown to be a source
      of IL-12 following TLR4-dependent activation by Salmonella (S.). In this study
      another antigen-presenting cell type, the conventional dendritic cell (cDC), was
      analyzed and its cytokine responses compared with those of MPhi. We generated
      bone marrow-derived conventional dendritic cells (BMDC) and macrophages (BMMPhi)
      by incubating murine bone marrow cells with supernatants containing
      granulocyte/macrophage colony-stimulating factor (GM-CSF) or macrophage colony
      stimulating factor (M-CSF), respectively. Stimulation of BMDC and BMMPhi with S.
      enterica serovar Enteritidis (SE) or LPS resulted in the release of IL-12 and IL
      23 by BMDC but not by BMMPhi. Furthermore, BMDC secreted approx. 20-fold more IL
      12p40 and IL-27p28 than BMMPhi. However, BMDC and BMMPhi produced similar levels
      of IL-10. Using BMDC originating from wild-type (wt), TLR2(def) and TLR4(def)
      mice, we show that in BMDC the induction of IL-12, IL-23, and IL-27p28 by SE is
      dependent on TLR4, whereas low-level production of p40 is also mediated by
      pattern recognition receptors (PRR) other than TLR4. Interestingly, LPS- and SE
      provoked responses of BMDC were remarkably similar indicating that LPS is the
      primary danger molecule of SE. Taken together, our results point to cDC rather
      than MPhi as the major producers of the IL-12 family members during in vitro
      infection with SE. The mechanisms of recognition of SE, however, appear to be the
      same for cDC and MPhi.

PMID- 18086376
TI  - Modulation of macrophage iron transport by Nramp1 (Slc11a1).
AB  - In mice, the expression of the phagolysosomal protein natural-resistance
      associated macrophage protein 1 (Nramp1, Slc11a1) is associated with host
      resistance to various intracellular pathogens. Nramp1 acts as a transporter for
      protons, iron, and other divalent cations, and Nramp1 functionality is associated
      with an enhanced activity of pro-inflammatory immune pathways, including the
      formation of nitric oxide (NO) via transcriptional stimulation of inducible
      nitric oxide synthase (iNOS) expression. As iron availability also strongly
      influences iNOS expression, we studied the effects of Nramp1 functionality on
      iron homeostasis in the RAW264.7 macrophage cell line stably transfected with
      functional or non-functional Nramp1. We found that macrophages lacking functional
      Nramp1 exhibited a significantly higher iron uptake via transferrin receptor 1
      and, as a consequence of this, an increased iron release which is mediated via
      the iron export protein ferroportin-1. RNA-bandshift experiments for
      determination of iron regulatory protein activity showed that, as a net effect of
      the altered expression of iron transporters, the overall cellular iron content
      was lower in macrophages bearing functional Nramp1. Since low intracellular iron
      availability enhances iNOS transcription, Nramp1 could exert its effect on NO
      formation and other pro-inflammatory immune pathways via modulation of iron
      homeostasis.

PMID- 18086377
TI  - N(2)O(3) enhances the nitrosative potential of IFNgamma-primed macrophages in
      response to Salmonella.
AB  - We show here that the nitric oxide (NO)-detoxifying Hmp flavohemoprotein
      increases by 3-fold the transcription of the Salmonella pathogenicity island 2
      (SPI2) in macrophages expressing a functional inducible NO synthase (iNOS).
      However, Hmp does not prevent NO-related repression of SPI2 transcription in
      IFNgamma-primed phagocytes, despite preserving intracellular transcription of
      sdhA sdhB subunits of Salmonella succinate dehydrogenase within both control and
      IFNgamma-primed phagocytes. To shed light into the seemingly paradoxical role
      that Hmp plays in protecting intracellular SPI2 expression in various populations
      of macrophages, N(2)O(3) was quantified as an indicator of the nitrosative
      potential of Salmonella-infected phagocytes in different states of activation.
      Hmp was found to prevent the formation of 300nM N(2)O(3)/h/bacteria in IFNgamma
      primed macrophages, accounting for about a 60% reduction of the nitrosative power
      of activated phagocytes. Utilization of the vacuolar ATPase inhibitor bafilomycin
      indicates that a fourth of the approximately 200nM N(2)O(3)/h sustained by
      IFNgamma-primed macrophages is generated in endosomal compartments via
      condensation of HNO(2). In sharp contrast, control macrophages infected with wild
      type Salmonella produce as little N(2)O(3) as iNOS-deficient controls.
      Collectively, these findings indicate that the NO-metabolizing activity of
      Salmonella Hmp is functional in both control and IFNgamma-primed macrophages.
      Nonetheless, a substantial amount of the NO generated by IFNgamma-primed
      macrophages gives rise to N(2)O(3), a species that not only enhances the
      nitrosative potential of activated phagocytes but also avoids detoxification by
      Salmonella Hmp.

PMID- 18086379
TI  - The molecular basis of macrophage fusion.
AB  - Multinucleated giant cells (MGCs), characteristic of granulomatous infections as
      well as multinucleated osteoclasts originate from fusion of macrophages. While
      intracellular and viral membrane fusion have been studied in detail, much less is
      known about the machinery which mediates cell-to-cell fusion, in particular
      macrophage polykaryon formation. Several molecules have been implicated in this
      process which may involve the action of multiple glycoproteins mediating membrane
      attachment and fusion. Macrophage fusion can be induced by soluble mediators such
      as cytokines and growth factors, even though several other stimuli may be
      involved, especially for the induction of granuloma-associated giant cells. The
      function of MGCs during granulomatous diseases is currently unknown. However, a
      better understanding of the mechanistic basis of macrophage fusion may lead to a
      better understanding of the function of MGCs found in granulomas.

PMID- 18086378
TI  - Emerging themes in IFN-gamma-induced macrophage immunity by the p47 and p65
      GTPase families.
AB  - Vertebrates have evolved complex immune specificity repertoires beyond the
      primordial components found in lower multi-cellular organisms to combat microbial
      infections. The type II interferon (IFN-gamma) pathway represents one such
      system, bridging innate and acquired immunity and providing host protection in a
      cell-autonomous manner. Recent large-scale transcriptome analyses of IFN-gamma
      dependent gene expression in effector cells such as macrophages have highlighted
      the prominence of two families of GTPases -- p47 IRGs and p65 GBPs -- that are
      now beginning to emerge as major determinants of antimicrobial resistance. Here
      we discuss the recent clarification of known family members, their cellular
      biochemistry and host defense functions as a means to understanding the complex
      innate immune response engendered in higher vertebrates such as humans and mice.

PMID- 18086381
TI  - Perspectives of mathematical modelling for understanding of intracellular
      signalling and vesicular trafficking in macrophages.
AB  - Macrophages are essential elements of the immune system that orchestrate
      activation and down-regulation of inflammatory reactions, tissue remodelling,
      healing processes and tissue homeostasis. Macrophages have to respond to complex
      signals specific for homeostatic or pathologic conditions. To retain sufficient
      accuracy of reaction, macrophages make use of the co-operative action of multiple
      extracellular factors that may amplify required activities and suppress undesired
      ones. This co-operativity is based on complex branching signalling networks
      coupled to positive and negative feedback loops; ligand uptake by scavenger
      receptors; intracellular sorting and multiple secretory pathways. Deregulation of
      co-operativity leads to pathological situations such as chronic inflammation,
      allergy, tumour initiation, and progression. The complexity of the system makes
      it impossible to assess the impact of every particular molecular event using
      classical molecular biological methodology. Mathematical modelling of signalling
      and membrane trafficking pathways using frameworks of differential equations will
      allow qualitative and quantitative description of macrophage behaviour in
      conditions simulating physiological situations. Although model construction
      requires large amounts of quantitative experimental data, the analysis of the
      model using mathematical methods enables the identification of the elements
      critical for the system. Established models may be used to simulate behaviour of
      macrophages under different conditions and to predict their reactions in vivo.
      Identified critical elements of the system will facilitate the isolation of
      predictive/diagnostic markers as well as potential therapeutic targets.

PMID- 18086380
TI  - Role of arginine metabolism in immunity and immunopathology.
AB  - A heterogeneous set of cells that are commonly grouped as "myeloid cells",
      interacts in a complex landscape of physiological and pathological situations. In
      this review we attempt to trace a profile of the "myeloid connection" through
      different normal and pathological states, by analyzing common metabolic pathways
      of the amino acid l-arginine. Myeloid cells exert various, often divergent,
      actions on the immune response through mechanisms that exploit mediators of this
      peculiar metabolic pathway, ranging from l-arginine itself to its downstream
      metabolites, like nitric oxide and polyamines. Various pathological situations,
      including neoplastic and autoimmune diseases, as well as injury repair and
      infections are discussed here, showing how l-arginine metabolism is able to play
      a dual role, both as an active protector and a possible threat to the organism.

PMID- 18086382
TI  - Infection of human dendritic cells with herpes simplex virus type 1 dramatically
      diminishes the mRNA levels of the prostaglandin E(2) receptors EP2 and EP4.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) of the
      immune system. Their migration to secondary lymphoid tissues is a crucial step
      for the priming of T cells and ultimately for the initiation of adaptive immune
      responses. Therefore, DCs are potential targets for immune evasion strategies of
      pathogens. The migration of DCs to the T cell areas of lymph nodes is guided by a
      gradient of chemokines, CCL19 and CCL21, which are constitutively expressed
      there. CCR7, the receptor for these chemokines, is expressed on activated DCs,
      enabling their homing to the lymph nodes. However, CCR7 expression alone is not
      sufficient for efficient migration. Prostaglandin E(2) (PGE(2)) is a mandatory
      factor for CCR7-mediated migration of DCs and exerts its effects via
      prostaglandin E(2) receptor 2 (EP2) and prostaglandin E(2) receptor 4 (EP4). In
      this study, we investigated the effect of herpes simplex virus type 1 (HSV-1)
      infection of mature monocyte-derived dendritic cells (MODCs) on the EP2 and EP4
      receptor expression. Affymetrix analyses and real-time polymerase chain reaction
      (PCR) demonstrated a dramatic down-regulation of the expression of those
      receptors. Additional real-time PCR and migration assays with a Deltavhs mutant
      virus lacking the virion host shutoff (vhs) gene implicate a vhs independent
      mechanism. Therefore, our results suggest a novel immune evasion strategy for HSV
      1.

PMID- 18086383
TI  - MCS-18, a novel natural product isolated from Helleborus purpurascens, inhibits
      dendritic cell activation and prevents autoimmunity as shown in vivo using the
      EAE model.
AB  - Here we report for the first time that MCS-18, a novel natural product isolated
      from Helleborus purpurascens, is able to inhibit the expression of typical
      molecules of mature dendritic cells (DC) such as CD80, CD86, and especially of
      CD83 subsequently leading to a clear and dose-dependent inhibition of the DC
      mediated T-cell stimulation. Furthermore, MCS-18 impeded the formation of the
      typical DC/T-cell clusters, which are essential to induce potent immune
      responses. Interestingly, MCS-18 also inhibited CCR7 expression on DC which
      subsequently lead to a dose-dependent block of the CCL19-mediated DC migration.
      MCS-18 not only inhibited the DC-mediated T-cell stimulation but also the anti
      CD3/anti-CD28-mediated T-cell stimulation. Strikingly, MCS-18 also strongly
      reduced the paralysis associated with the experimental autoimmune
      encephalomyelitis (EAE), which is a murine model for human multiple sclerosis, in
      a prophylactic as well as in a "real" therapeutic setting. Even when the EAE was
      induced for a second time, the MCS-18-treated animals were still protected,
      suggesting that MCS-18 induces a long-lasting suppressive effect. In addition,
      and very important for the potential practical application in humans, MCS-18 was
      also active when administered orally. MCS-18 treatment almost completely reduced
      leukocyte infiltration in the brain and in the spinal cord. In conclusion, using
      in vitro as well in vivo assays we were able to show that MCS-18 exerts a strong
      immunosuppressive activity with remarkable potential for the therapy of diseases
      characterized by a pathologically over-activated immune system.

PMID- 18086384
TI  - Factors influencing the generation of murine dendritic cells from bone marrow:
      the special role of fetal calf serum.
AB  - Since the generation of dendritic cells (DC) from myeloid precursor cells within
      the bone marrow (BM) was first reported, it has developed to one of the standard
      tools for studying DC biology in rodent systems. However, antigen-specific
      effects of such DC on polyclonal T cell populations may be influenced by the
      additional presentation of bystander antigens derived from fetal calf sera (FCS).
      This may lead to misinterpretations of the antigen-specific effects on the T cell
      response. In addition, many factors, including FCS, also influence the quantity
      and quality of BM-DC already during culture. Here, we review the factors that
      have an impact on the generation of BM-DC, including criteria regarding the mice,
      but also technical parameters and the different growth factors. The critical role
      of FCS in BM-DC cultures and alternative methods using murine sera or serum-free
      media are discussed.

PMID- 18086386
TI  - Infection of mature dendritic cells with herpes simplex virus type 1 interferes
      with the interferon signaling pathway.
AB  - It has been shown that herpes simplex virus type 1 (HSV-1) blocks specific immune
      responses by various mechanisms. Cell lines infected with HSV-1 for instance show
      a severe impairment of the interferon-gamma (IFN-gamma)-induced signal transducer
      and activator of transcription 1 (STAT1) signaling pathway. Thus, we examined the
      influence of HSV-1 infection on IFN-gamma signal transduction in mature dendritic
      cells (mDCs). In this study, we report the down-regulation of the IFN-gamma
      receptor alpha chain (IFNGR1) at the mRNA level in HSV-1 infected mDCs. As a
      consequence, the expression of the IFNGR1 subunit on the cell surface of the
      infected cell was strongly reduced. Furthermore, we were able to show the
      inhibition of STAT1 phosphorylation following HSV-1 infection in mDCs, while
      protein levels of STAT1 remained constant. As a direct downstream effect of STAT1
      phosphorylation, the activation of the transcription factor IRF-1 was also
      clearly inhibited and could no longer be induced by the addition of IFN-gamma.
      Additional experiments using a virus strain lacking the vhs gene suggested that
      the mutant virus is more sensitive to IFN-gamma as STAT1 signaling was inhibited
      to a lesser extent. Infection with a UV-inactivated, replication incompetent
      virus did not influence the STAT1 signaling pathway at all. In conclusion, we
      show that HSV-1 blocks IFN-gamma signaling in mDCs, which requires viral gene
      expression and involves the viral protein vhs.

PMID- 18086385
TI  - Organ-specific and differential requirement of TYK2 and IFNAR1 for LPS-induced
      iNOS expression in vivo.
AB  - Lipopolysaccharide (LPS) is an integral structural component of the outer
      membrane of Gram-negative bacteria and the principal active agent in the
      pathogenesis of endotoxin shock. LPS is a potent inducer of a variety of
      cytokines and inflammatory agents that lead to a profound alteration of gene
      expression patterns in cells and organs. The gene coding for the inducible nitric
      oxide synthase (iNOS) is highly responsive to LPS in vitro and in vivo and
      accounts for the production of nitric oxide (NO). The Janus kinase (JAK) family
      member tyrosine kinase 2 (TYK2) is a constituent of the interferon (IFN) type I
      response pathway and an important effector in the progression of endotoxin shock.
      Macrophages deficient for IFNalphabeta receptor chain 1 (IFNAR1) or TYK2 were
      shown to have an impaired LPS-induced iNOS expression. Here we determined the
      contribution of IFNAR1 and TYK2 to iNOS expression in vivo in a lethal LPS
      challenge model. TYK2 and IFNAR1 were found to be crucial for the LPS-induced
      iNOS mRNA and protein expression in spleen and lung that could be attributed to
      the Mac3-positive population. In liver LPS-induced iNOS mRNA expression was only
      partially impaired in TYK2-deficient mice and was unimpaired in IFNAR1-deficient
      mice, indicating organ specificity. TYK2(-/-) and IFNAR1(-/-) mice also differ
      with respect to IFNgamma production upon LPS challenge in that TYK2(-/-) mice
      show a defect while IFNAR1(-/-) mice do not. Our data suggest that iNOS is
      induced through IFNAR1 and TYK2 in Mac3-positive cells which are the main source
      of iNOS in spleen and lung. The LPS-induced iNOS expression in liver is
      independent of IFNAR1 and partially dependent on TYK2, which is most likely due
      to the lack of IFNgamma production in the absence of TYK2.

PMID- 18086387
TI  - Matrix protein mediated shutdown of host cell metabolism limits vesicular
      stomatitis virus-induced interferon-alpha responses to plasmacytoid dendritic
      cells.
AB  - Upon infection with many different viruses, plasmacytoid dendritic cells (pDC)
      produce large amounts of type I interferon (IFN-alpha/beta). To address why upon
      vesicular stomatitis virus (VSV) infection pDC, but not conventional myeloid DC
      (mDC), are induced to produce IFN-alpha, pDC and mDC were differentiated from
      bone marrow cells (BM-DC). Upon VSV infection BM-pDC produced IFN-alpha, whereas
      BM-mDC did not. Notably, upon infection with VSV-M2, a VSV variant expressing a
      M51R mutant matrix (M) protein that showed a reduced sequestration of host cell
      metabolism, BM-pDC and BM-mDC mounted massive IFN-alpha responses. Both DC
      subsets showed comparable RNA levels of retinoic acid inducible gene-I (RIG-I)
      and Toll-like receptor (TLR) 7 and were able to respond upon triggering with
      double-stranded RNA (dsRNA) or single-stranded RNA (ssRNA) analogs. Moreover,
      upon VSV-M2 infection IFN-alpha production by both DC subsets was largely
      dependent on viral replication. Interestingly, upon virus infection BM-pDC, but
      not BM-mDC, up-regulated mRNA levels of nuclear export factors Nup96/98, probably
      reflecting cellular mechanisms to circumvent viral escape strategies.
      Collectively, these results indicated that cell types induced to produce IFN
      alpha upon viral infection are not primarily defined by cellular receptor
      configurations but rather by complex virus/host cell interactions.

PMID- 18086389
TI  - Excerpts from the United States Renal Data System 2007 annual data report.

PMID- 18086388
TI  - Molecular mechanisms of the anti-inflammatory functions of interferons.
AB  - Interferons are pleiotropic cytokines with important proinflammatory functions
      required in defence against infections with bacteria, viruses and multicellular
      parasites. In recent years, fundamental functions of interferons in other
      processes such as cancer immunosurveillance, immune homeostasis and
      immunosuppression have been established. In addition, anti-inflammatory roles of
      interferons are well-documented in several inflammatory disease models in the
      mouse, most importantly in experimental autoimmune encephalomyelitis that
      resembles multiple sclerosis in humans. While the beneficial effects of
      interferons in such disease models are known, the molecular mechanisms remain
      poorly understood. Only recently a few molecular principles for the anti
      inflammatory properties of interferons at the cellular level have been revealed.
      They include the ability of interferons to reduce the expression of the receptors
      for the inflammation-related cytokines IL-1 and IL-4, or to increase the
      expression of the potent anti-inflammatory genes tristetraprolin and Twist.
      However, the individual contribution of these anti-inflammatory responses to the
      overall beneficial effects of interferons in inflammatory diseases is still an
      open question. Also, the reason for the apparently limited number of tissues that
      are susceptible to the anti-inflammatory functions of interferons remains
      enigmatic. This review summarizes the present knowledge of the anti-inflammatory
      effects of interferons, and describes the currently known molecular mechanisms
      that may help explain the benefits of interferon signalling in several
      inflammatory diseases.

PMID- 18086390
TI  - Radiobiologic significance of response of intratumor quiescent cells in vivo to
      accelerated carbon ion beams compared with gamma-rays and reactor neutron beams.
AB  - PURPOSE: To clarify the radiosensitivity of intratumor quiescent cells in vivo to
      accelerated carbon ion beams and reactor neutron beams. METHODS AND MATERIALS:
      Squamous cell carcinoma VII tumor-bearing mice were continuously given 5-bromo-2'
      deoxyuridine to label all intratumor proliferating cells. Next, they received
      accelerated carbon ion or gamma-ray high-dose-rate (HDR) or reduced-dose-rate
      (RDR) irradiation. Other tumor-bearing mice received reactor thermal or
      epithermal neutrons with RDR irradiation. Immediately after HDR and RDR
      irradiation or 12 h after HDR irradiation, the response of quiescent cells was
      assessed in terms of the micronucleus frequency using immunofluorescence staining
      for 5-bromo-2'-deoxyuridine. The response of the total (proliferating plus
      quiescent) tumor cells was determined from the 5-bromo-2'-deoxyuridine nontreated
      tumors. RESULTS: The difference in radiosensitivity between the total and
      quiescent cell populations after gamma-ray irradiation was markedly reduced with
      reactor neutron beams or accelerated carbon ion beams, especially with a greater
      linear energy transfer (LET) value. Clearer repair in quiescent cells than in
      total cells through delayed assay or a decrease in the dose rate with gamma-ray
      irradiation was efficiently inhibited with carbon ion beams, especially with a
      greater LET. With RDR irradiation, the radiosensitivity to accelerated carbon ion
      beams with a greater LET was almost similar to that to reactor thermal and
      epithermal neutron beams. CONCLUSION: In terms of tumor cell-killing effect as a
      whole, including quiescent cells, accelerated carbon ion beams, especially with
      greater LET values, are very useful for suppressing the dependency on the
      heterogeneity within solid tumors, as well as depositing the radiation dose
      precisely.

PMID- 18086391
TI  - Reproducibility of intratumor distribution of (18)F-fluoromisonidazole in head
      and neck cancer.
AB  - PURPOSE: Hypoxia is one of the main causes of the failure to achieve local
      control using radiotherapy. This is due to the increased radioresistance of
      hypoxic cells. (18)F-fluoromisonidazole ((18)F-FMISO) positron emission
      tomography (PET) is a noninvasive imaging technique that can assist in the
      identification of intratumor regions of hypoxia. The aim of this study was to
      evaluate the reproducibility of (18)F-FMISO intratumor distribution using two
      pretreatment PET scans. METHODS AND MATERIALS: We enrolled 20 head and neck
      cancer patients in this study. Of these, 6 were excluded from the analysis for
      technical reasons. All patients underwent an (18)F-fluorodeoxyglucose study,
      followed by two (18)F-FMISO studies 3 days apart. The hypoxic volumes were
      delineated according to a tumor/blood ratio >or=1.2. The (18)F-FMISO tracer
      distributions from the two (18)F-FMISO studies were co-registered on a voxel-by
      voxel basis using the computed tomography images from the PET/computed tomography
      examinations. A correlation between the (18)F-FMISO intensities of the
      corresponding spatial voxels was derived. RESULTS: A voxel-by-voxel analysis of
      the (18)F-FMISO distributions in the entire tumor volume showed a strong
      correlation in 71% of the patients. Restraining the correlation to putatively
      hypoxic zones reduced the number of patients exhibiting a strong correlation to
      46%. CONCLUSION: Variability in spatial uptake can occur between repeat (18)F
      FMISO PET scans in patients with head and neck cancer. Blood data for one patient
      was not available. Of 13 patients, 6 had well-correlated intratumor distributions
      of (18)F-FMISO-suggestive of chronic hypoxia. More work is required to identify
      the underlying causes of changes in intratumor distribution before single-time
      point (18)F-FMISO PET images can be used as the basis of hypoxia-targeting
      intensity-modulated radiotherapy.

PMID- 18086393
TI  - In regards to Glatstein: restrictions of a statistical mind: clinical relevance
      versus P values or when less is more (Int J Radiat Oncol Biol Phys 2007;68:322
      323).

PMID- 18086392
TI  - Accelerated partial-breast intensity-modulated radiotherapy results in improved
      dose distribution when compared with three-dimensional treatment-planning
      techniques.
AB  - PURPOSE: To compare dose distribution and normal tissue sparing in partial-breast
      treatment using three-dimensional conformal radiotherapy (3D-CRT) vs. intensity
      modulated radiotherapy (IMRT). METHODS AND MATERIALS: Sixty-three patients with
      Tis-1N0M0 breast cancer were treated on a Phase II prospective accelerated
      partial-breast IMRT protocol at two facilities between April 2004 and January
      2006. Fifty-six patients had data sets sufficient to adequately contour all
      structures. These cases were subsequently replanned with 3D-CRT techniques using
      the same contours, to compare the dose distribution patterns of 3D-CRT vs. IMRT.
      RESULTS: The average planning target volume (PTV) to ipsilateral breast (IB)
      ratio was 24% (range, 7-58%). The average volume of IB receiving 25%, 50%, 75%,
      and 100% of the prescribed dose was 4.0%, 5.0%, 5.5%, and 10.5% less with IMRT
      than with 3D (p < 0.01). The dose reduction to normal breast was further improved
      in the subset of patients whose PTV to IB ratio was >25%, and in patients with
      contoured breast volume <750 cm(3). No difference was detected in delivery to the
      lumpectomy cavity or clinical target volume. The PTV volume receiving 95% of the
      dose was higher in the 3D conformal plans (p < 0.01), but no significant
      difference was observed in the PTV volume receiving 90% (p = 0.17). The
      irradiated heart and lung volumes were small with both techniques but also
      favored IMRT. CONCLUSIONS: In T1N0 patients treated with external beam partial
      breast radiotherapy, IMRT improves normal tissue sparing in the ipsilateral
      breast compared with 3DRT, without compromising dose delivery to the lumpectomy
      cavity and clinical target volume.

PMID- 18086395
TI  - On the future of critical care medicine.

PMID- 18086396
TI  - Quality measurement at intensive care units: which indicators should we use?
AB  - OBJECTIVE: This study was conducted to develop a set of indicators that measure
      the quality of care in intensive care units (ICU) in Dutch hospitals and to
      evaluate the feasibility of the registration of these indicators. METHODS: To
      define potential indicators for measuring quality, 3 steps were made. First, a
      literature search was carried out to obtain peer-reviewed articles from 2000 to
      2005, describing process or structure indicators in intensive care, which are
      associated with patient outcome. Additional indicators were suggested by a panel
      of experts. Second, a selection of indicators was made by a panel of experts
      using a questionnaire and ranking in a consensus procedure. Third, a study was
      done for 6 months in 18 ICUs to evaluate the feasibility of using the identified
      quality indicators. Site visits, interviews, and written questionnaires were used
      to evaluate the use of indicators. RESULTS: Sixty-two indicators were initially
      found, either in the literature or suggested by the members of the expert panel.
      From these, 12 indicators were selected by the expert panel by consensus. After
      the feasibility study, 11 indicators were eventually selected. "Interclinical
      transport," referring to a change of hospital, was dropped because of lack of
      reliability and support for further implementation by the participating hospitals
      in the study. The following structure indicators were selected: availability of
      intensivist (hours per day), patient-to-nurse ratio, strategy to prevent
      medication errors, measurement of patient/family satisfaction. Four process
      indicators were selected: length of ICU stay, duration of mechanical ventilation,
      proportion of days with all ICU beds occupied, and proportion of glucose
      measurement exceeding 8.0 mmol/L or lower than 2.2 mmol/L. The selected outcome
      indicators were as follows: standardized mortality (APACHE II), incidence of
      decubitus, number of unplanned extubations. The time for registration varied from
      less than 30 minutes to more than 1 hour per day to collect the items. Among
      other factors, this variation in workload was related to the availability of
      computerized systems to collect the data. CONCLUSION: In this study, a set of 11
      quality indicators for intensive care was defined based on literature research,
      expert opinion, and testing. The set gives a quick view of the quality of care in
      individual ICUs. The availability of a computerized data collection system is
      important for an acceptable workload.

PMID- 18086398
TI  - Venous thromboembolism in critical illness in a community intensive care unit.
AB  - BACKGROUND: Venous thromboembolism (VTE) can be a life-threatening complication
      of critical illness. Venous thromboembolism rates observed depend on the
      population studied, the screening modality used, and thromboprophylaxis
      prescribed. Few studies report on the rates of clinically diagnosed VTE in
      critically ill patients. The purpose of this study was to characterize the
      incidence of clinically diagnosed VTE, prophylactic strategies used, and
      diagnostic studies ordered in a critically ill population at a tertiary community
      intensive care unit (ICU), both during and after their ICU stay. METHODS: We did
      a retrospective chart review of 600 consecutive critically ill patients admitted
      to a tertiary community ICU. RESULTS: Fifty (8.3%) patients developed VTE over
      the course of their ICU and hospital stay (18 [3.0%] patients during their ICU
      stay and 32 [5.7% of 561 ICU survivors] patients after ICU discharge). By ICU
      admission diagnosis, most events occurred in neurosurgical patients, although
      this group comprised only 24.8% of the population. Across all subgroups, most VTE
      events occurred after ICU discharge. Intensive care unit patients received
      thromboprophylaxis 87.6% (95% confidence interval, 81.5-93.7) of the time spent
      in ICU. However, thromboprophylaxis was administered significantly less often
      after transfer to the ward compared with within the ICU (from 87.6% to 59.8%, P <
      .001). CONCLUSION: The rates of clinically diagnosed VTE rates in critically ill
      patients are substantial. Venous thromboembolism occurs before, during, and after
      ICU discharge. Continued vigilance and thromboprophylaxis are warranted across
      the continuum of critical illness.

PMID- 18086397
TI  - Intensive care unit exposures for long-term outcomes research: development and
      description of exposures for 150 patients with acute lung injury.
AB  - PURPOSE: Long-term follow-up studies in critical care have described survivors'
      outcomes, but provided less insight into the patient/disease characteristics and
      intensive care therapies ("exposures") associated with these outcomes. Such
      insights are essential for improving patients' long-term outcomes. This report
      describes the development of a strategy for comprehensively measuring relevant
      exposures for long-term outcomes research, and presents empiric results from its
      implementation. MATERIALS AND METHODS: A multistep, iterative process was used to
      develop the exposures strategy. First, a comprehensive list of potential
      exposures was generated and subsequently reduced based on feasibility,
      redundancy, and relevance criteria. Next, data abstraction methods were designed
      and tested. Finally, the strategy was implemented in 150 patients with acute lung
      injury with iterative refinement. RESULTS: The strategy resulted in the
      development of more than 60 unique exposures requiring less than 45 minutes per
      patient-day for data collection. Most exposures had minimal missing data and
      adequate reliability. These data revealed that evidence-based practices including
      lower tidal volume ventilation, spontaneous breathing trials, sedation
      interruption, adequate nutrition, and blood glucose of less than 6.1 mmol/L (110
      mg/dL) occurred in only 23% to 50% of assessments. CONCLUSIONS: Using a
      multistep, iterative process, a comprehensive and feasible exposure measurement
      strategy for long-term outcomes research was successfully developed and
      implemented.

PMID- 18086399
TI  - Interhospital transfer of critically ill patients: demographic and outcomes
      comparison with nontransferred intensive care unit patients.
AB  - PURPOSE: We examined the association between access to intensive care services
      and mortality in a cohort of critically ill patients. MATERIALS AND METHODS: We
      conducted an observational study involving 6298 consecutive admissions to the
      intensive care units (ICUs) of a tertiary care hospital. Data including
      demographics, admission source, and outcomes were collected on all patients.
      Admission source was classified as "transfer" for patients admitted to the ICU
      from other hospitals, "ER" for patients admitted from the emergency room, and
      "ward" for patients admitted from non-ICU inpatient wards. RESULTS: Transfer
      patients had higher crude ICU and hospital mortality rates compared with
      emergency room admissions (crude odds ratio [OR], 1.51; 95% confidence interval
      [CI], 1.32-1.75). After adjusting for age, sex, diagnosis, comorbidities, and
      acute physiology scores, the difference in ICU mortality remained significant
      (OR, 1.30; 95% CI, 1.09-1.56); however, hospital mortality did not (OR, 1.19; 95%
      CI, 1.00-1.41). Compared with ward patients, transfer from other hospitals was
      associated with lower hospital mortality after adjusting for severity of illness
      and other case-mix variables (OR, 0.81; 95% CI, 0.68-0.95). CONCLUSIONS: We found
      some evidence to suggest that differential access to intensive care services
      impacts mortality within this case mix of patients. These findings may have
      implications for current efforts to centralize and regionalize critical care
      services.

PMID- 18086400
TI  - Two perspectives on organ donation: experiences of potential donor families and
      intensive care physicians of the same event.
AB  - The aim was to explore how relatives and physicians understood cases where organ
      donation had been requested and what factors were salient for the decision on
      donation. Physicians of 25 deceased patients and 20 relatives were interviewed.
      The material was analyzed using qualitative methods. Eleven patients had declared
      their wishes on donation before death; in 14 cases the relatives had to decide.
      Half of these relatives accepted donation and half refused. The donation request
      was of secondary importance to the families; they were totally occupied by the
      death and initially tried to avoid the request by regarding "no" as a
      nonresponse. They needed support to relieve their immediate reactions of
      uneasiness, start rational thought processes, and reach well-grounded answers.
      The basis for requesting donation was good; relatives, with regard to
      circumstances, had been well prepared for the death by continuous information
      from the physicians and had confidence in staff, accepted that the question was
      raised, and understood the death criteria. However, about half the physicians
      experienced conflicts regarding prerequisites of procuring organs and dealing
      with relatives. Three different approaches were displayed: prodonation, neutral,
      and ambivalent. Only physicians with a prodonation approach received acceptance
      for donation.

PMID- 18086401
TI  - Hypercapnic acidosis modulates inflammation, lung mechanics, and edema in the
      isolated perfused lung.
AB  - OBJECTIVE: Low tidal volume (V(T)) ventilation strategies may be associated with
      permissive hypercapnia, which has been shown by ex vivo and in vivo studies to
      have protective effects. We hypothesized that hypercapnic acidosis may be
      synergistic with low V(T) ventilation; therefore, we studied the effects of
      hypercapnia and V(T) on unstimulated and lipopolysaccharide-stimulated isolated
      perfused lungs. MATERIALS AND METHODS: Isolated perfused rat lungs were
      ventilated for 2 hours with low (7 mL/kg) or moderately high (20 mL/kg) V(T) and
      5% or 20% CO(2), with lipopolysaccharide or saline added to the perfusate.
      RESULTS: Hypercapnia resulted in reduced pulmonary edema, lung stiffness, tumor
      necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the lavage and
      perfusate. The moderately high V(T) did not cause lung injury but increased
      lavage IL-6 and perfusate IL-6 as well as TNF-alpha. Pulmonary edema and
      respiratory mechanics improved, possibly as a result of a stretch-induced
      increase in surfactant turnover. Lipopolysaccharide did not induce significant
      lung injury. CONCLUSIONS: We conclude that hypercapnia exerts a protective effect
      by modulating inflammation, lung mechanics, and edema. The moderately high V(T)
      used in this study stimulated inflammation but paradoxically improved edema and
      lung mechanics with an associated increase in surfactant release.

PMID- 18086402
TI  - Adrenal insufficiency in early phase of pediatric acute lung injury/acute
      respiratory distress syndrome.
AB  - INTRODUCTION: Adequate adrenal function is essential to survive critical illness.
      Several recent articles have reported the significant effect of adrenal
      insufficiency (AI) in patients with sepsis. However, the prevalence of AI in
      pediatric acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is
      so far still scanty. Thus, we elected to study its prevalence and its clinical
      outcome. METHODS: This is a cross-sectional observational study. We enrolled
      eligible infants and children aged between 1 month and 15 years who were admitted
      to our tertiary pediatric intensive care unit from February 1, 2005, to December
      31, 2005, with ALI or ARDS diagnosed by the American-European Consensus criteria.
      A short corticotropin stimulation test (250 microg) was done within 24 hours of
      enrollment, and all clinical data were also recorded. Cortisol levels were
      measured at baseline, 30 minutes, and 60 minutes posttest. Adrenal insufficiency
      was defined as a baseline cortisol level of less than 15.1 microg/dL or an
      increment of cortisol level of less than 9 microg/dL after the
      adrenocorticotropic hormone stimulation test. RESULTS: Of 507 patients admitted
      to the pediatric intensive care unit, there were 20 diagnosed with ALI/ARDS. Of
      20 children, 16 met the inclusion criteria and had none of the exclusion
      criteria. Of 16, there were 9 (56%) with ARDS, and 7 (44%) of 12 had ALI. The
      prevalence of AI was observed in 37.5% (6/16), diagnosed by baseline level
      criteria in 25% (4/16) and by incremental criteria in 12.5% (2/16). The Baseline
      level of the adrenocorticotropic hormone was 7.8 +/- 5 (nmol/L). The median age
      in the AI group was 2 months. Of 6 children, 5 (83.3%) were in the ARDS group.
      Pediatric Risk of Mortality III score was significantly higher in the AI group
      compared with that in the non-AI (P < .05). Initial Pao(2)/fraction of inspired
      oxygen ratio tended to be lower in the AI group (123.2 +/- 62.2) compared with
      that in the non-AI group (183.8 +/- 79.1), although not statistically significant
      (P = .1). The mortality was also not statistically different between the AI (1/6,
      16.7%) and the non-AI groups (1/10, 10%). CONCLUSIONS: Our study demonstrated
      that the prevalence of AI was common in pediatric ALI/ARDS. These results would
      be an initial step to further study the impact of AI on clinical outcomes of
      these children in a larger scale.

PMID- 18086403
TI  - Adrenal exhaustion in septic patients with vasopressor dependency.
AB  - PURPOSE: The use of low-dose corticosteroids for patients with septic shock who
      remain vasopressor dependent after adequate fluid resuscitation is recommended,
      but there is lack of agreement on how to diagnose relative adrenal insufficiency
      (RAI) and when to start steroid supplementation among these patients. This case
      series reports changes in cortisol concentrations during the course of
      vasopressor-dependent septic shock. METHODS: Observational study was performed at
      a university hospital medical intensive care unit. Consecutive adult patients
      with vasopressor-dependent septic shock admitted to the medical intensive care
      unit were studied. Clinical data, cortisol concentrations, and dose of
      vasopressor agents at different times during the course of septic shock were
      recorded and reported as mean +/- SD. RESULTS: Thirteen patients were included.
      Mean age was 59 +/- 15 years. Mean basal nonstimulated cortisol level was 41.7 +/
      30.9 microg/dL (within 24 hours of intensive care unit admission in all but 2
      patients). Steroids were initiated in 8 patients and then discontinued after
      cortisol values were obtained and RAI was ruled out. Because of inability to
      discontinue vasopressor support, cortisol testing was repeated after 6.2 +/- 4.8
      days of initial assessment. Repeated concentrations were 10.0 +/- 6.3 mug/dL (P <
      .001). Steroids were then reinitiated, and resolution of vasopressor dependence
      was achieved 1.5 +/- 1.4 days later. CONCLUSIONS: Adrenal function in the
      critically ill is a dynamic process, and an appropriate initial adrenal response
      does not preclude later development of RAI.

PMID- 18086404
TI  - Low-dose steroid therapy does not affect hemodynamic response in septic shock
      patients.
AB  - PURPOSE: Several studies showed that low-dose steroid therapy (LDST) in patients
      with septic shock leads to a significantly shorter duration of shock and a
      decreased mortality. However, these results have been criticized. Our purpose was
      to evaluate the effects of LDST on time to shock reversal and mortality in septic
      shock. MATERIALS AND METHODS: We retrospectively studied 203 patients with septic
      shock admitted to the intensive care unit of our tertiary hospital. A short
      corticotropin test was performed in all patients within 72 hours of septic shock
      onset. We performed a propensity score analysis through a logistic regression
      model with baseline relevant characteristics, and evaluated the influence of LDST
      on time to shock reversal and inhospital mortality. RESULTS: One hundred twenty
      four patients were treated with LDST (steroid group) and 79 without LDST (control
      group). Patients treated with steroids presented higher Simplified Acute
      Physiology Score II and maximum Sepsis-Related Organ Failure Assessment scores.
      Both groups presented similar baseline and stimulated cortisol values. The hazard
      ratio of remaining on shock adjusted by severity of illness, inadequate
      antibiotic, and propensity score was 1.15 (95% confidence interval 0.71-1.86) for
      patients treated with steroids. Inhospital mortality was 62% in the steroid group
      and 52% in the control group (P = .84). Logistic regression analysis with
      propensity score neither showed differences between steroid and control group in
      the inhospital mortality. Predictors of inhospital mortality were age, maximum
      Sepsis-Related Organ Failure Assessment score, and inadequate antibiotics.
      CONCLUSION: In our study, treatment with low-dose steroid therapy was not
      associated to a reduction in time to shock reversal or mortality.

PMID- 18086405
TI  - Corticosteroids for sepsis: controversial forever?

PMID- 18086407
TI  - Global molecular epidemiology of HIV: understanding the genesis of AIDS pandemic.

PMID- 18086408
TI  - Current clinical treatments of AIDS.

PMID- 18086409
TI  - HIV-1-specific immune response.

PMID- 18086410
TI  - Targeting HIV attachment and entry for therapy.

PMID- 18086411
TI  - Inhibitors of HIV-1 reverse transcriptase.

PMID- 18086412
TI  - Development of protease inhibitors and the fight with drug-resistant HIV-1
      variants.

PMID- 18086413
TI  - HIV-1 integrase inhibitors: update and perspectives.

PMID- 18086414
TI  - Topical microbicides: a promising approach for controlling the AIDS pandemic via
      retroviral zinc finger inhibitors.

PMID- 18086415
TI  - Viral drug resistance and fitness.

PMID- 18086416
TI  - Gene therapy to induce cellular resistance to HIV-1 infection: lessons from
      clinical trials.

PMID- 18086417
TI  - Identification of potential drug targets using genomics and proteomics: a systems
      approach.

PMID- 18086418
TI  - Rapid disease progression to AIDS due to Simian immunodeficiency virus infection
      of macaques: host and viral factors.

PMID- 18086419
TI  - Nonprimate models of HIV-1 infection and pathogenesis.

PMID- 18086420
TI  - Perspectives for a protective HIV-1 vaccine.

PMID- 18086421
TI  - Molecular mechanisms of HIV-1 vertical transmission and pathogenesis in infants.

PMID- 18086424
TI  - Postliver transplantation vascular and biliary surgical anatomy.
AB  - Imaging and management of postliver transplantation complications require an
      understanding of the surgical anatomy of liver transplantation. There are several
      methods of liver transplantation. Furthermore, liver transplantation is a complex
      surgery with numerous variables in its 4 anastomoses: (1) arterial anastomosis,
      (2) venous inflow (portal venous) anastomosis, (3) venous outflow (hepatic vein,
      inferior vena cava, or both) anastomosis, and (4) biliary/biliary-enteric
      anastomosis. The aim of this chapter is to introduce the principles of liver
      transplant surgical anatomy based on anastomotic anatomy. With radiologists as
      the target readers, the chapter focuses on the inflow and outflow connections and
      does not detail intricate surgical techniques or intraoperative maneuvers,
      operative stages, or vascular shunting.

PMID- 18086425
TI  - Noninvasive imaging of liver transplant complications.
AB  - Noninvasive cross-sectional imaging modalities include ultrasound, computerized
      tomography, and magnetic resonance imaging. Each of these imaging methods has
      unique applications for vascular imaging. This article will review the technical
      parameters of each of the 3 modalities, including specialized vascular
      techniques. The main vascular transplant complications will then be discussed
      with respect to the diagnostic criteria and applicability of each of the relevant
      modalities. Transplant complications including hepatic artery stenosis and
      thrombosis, stenosis and thrombosis of the portal vein or inferior vena cava, and
      hepatic vein stenosis will be discussed. Sequelae of hepatic artery stenosis
      including biliary necrosis will also be reviewed briefly.

PMID- 18086426
TI  - Management of hepatic artery steno-occlusive complications after liver
      transplantation.
AB  - Steno-occlusive disease (arterial obstructive disease) of the transplant hepatic
      artery is a collective term that can be used to include hepatic artery
      thrombosis, hepatic artery stenosis, and hepatic arterial kinks. The latter 2 can
      be referred to collectively as arterial anatomical defects. This chapter details
      the angiographic techniques and definitions required to make an accurate
      angiographic diagnosis of these arterial transplant complications. In addition,
      the chapter focuses on detailed technical aspects of the endoluminal management
      of these arterial complications. The chapter discusses the role and technical
      results of endoluminal management of these arterial complications and, when
      possible, the lesion morphologies most amenable to endoluminal management.

PMID- 18086427
TI  - Management of nonocclusive hepatic artery complications after liver
      transplantation.
AB  - Nonocclusive arterial disease represents less than 5% of posttransplant arterial
      complications. Nonocclusive arterial complications are classified into (1)
      nonocclusive diminished flow in the hepatic artery, (2) arteriovenous fistulae,
      (3) pseudoaneurysms, and (4) arterial rupture. Due to the rarity of these
      complications, particularly when considering them individually, many of the
      opinions and managements of these complications are anecdotal. Transcatheter
      embolization is the main mode of minimal invasive management of these uncommon
      complications. Other minimal invasive methods have been described such as stent
      placement or direct percutaneous embolization/thrombosis. The article discusses
      the presentation, etiology, types, treatment indications, and various modes of
      minimal invasive therapy used to manage these complications.

PMID- 18086422
TI  - The viral etiology of AIDS-associated malignancies.

PMID- 18086428
TI  - Management of portal venous complications after liver transplantation.
AB  - The postoperative vascular complications following liver transplantation,
      specifically portal venous complications, have been well documented. These
      complications, which include portal venous stenosis and thrombosis, can be
      potentially devastating and lead to graft failure. The interventional techniques
      in managing these complications are relatively new and have been developed only
      in the past 15 to 20 years. Additionally with the increasing numbers of split
      liver and living related transplants that are being performed, so has the
      incidence of portal venous complications increased. This article is a review of
      the current interventional techniques used in managing portal venous
      complications in the posttransplant patient. The topics covered include portal
      vein angioplasty, stenting, and thrombolysis with a description of the variety of
      techniques used to perform these procedures. The review also covers management of
      portal hypertension by creating a transjugular intrahepatic portosystemic shunt
      (TIPS).

PMID- 18086429
TI  - Management of venous outflow complications after liver transplantation.
AB  - Liver transplantation can be complicated by stenosis of the hepatic venous or
      inferior vena cava outflow. Venous outflow stenosis occurs at rates of 1 to 6%
      depending on the type of anastomosis. Stenoses can develop acutely as a result of
      technical problems or can present much later after the transplant due to intimal
      hyperplasia or perianastomotic fibrosis. Common clinical presentations include
      hepatic dysfunction, liver engorgement, ascites, abdominal pain, and occasionally
      variceal bleeding. Treatment can generally be accomplished via a transjugular
      approach, but percutaneous transhepatic access may be needed when the anastomosis
      cannot be catheterized from the jugular access. Angioplasty can achieve technical
      success in restoring anastomotic patency in close to 100% of cases, but
      restenosis is frequent. Repeat angioplasties may be needed. In adults and
      pediatric patients with adult sized hepatic veins, stenting may be a better
      option. Resolution of clinical signs and symptoms is seen in 73 to 100% of cases.
      Major complications are uncommon, with stent migration being one of the more
      difficult complications to manage.

PMID- 18086430
TI  - The dilemma of digital imaging in retinopathy of prematurity.

PMID- 18086431
TI  - Amniotic membrane therapy in the acute phase of toxic epidermal necrolysis.

PMID- 18086433
TI  - Oxybutynin-associated esotropia.
AB  - A 5-year-old girl with previously unrecognized hyperopia of approximately +3.00 D
      developed esotropia while being treated with oxybutynin for enuresis. The
      esotropia disappeared with cessation of oxybutynin and correction of her
      hyperopia. When the hyperopic correction was removed, she had a small esophoria.
      The esotropia was presumably triggered by the anticholinergic effect of
      oxybutynin, which reduced the ability to accommodate. The increased accommodative
      effort for vision generated an esotropia as a result of the accommodative
      convergence/accommodation ratio.

PMID- 18086432
TI  - Cataracts in congenital toxoplasmosis.
AB  - PURPOSE: To determine the incidence and natural history of cataracts in children
      with congenital toxoplasmosis. METHODS: Children referred to the National
      Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS) between 1981
      and 2005 were examined by ophthalmologists at predetermined times according to a
      specific protocol. The clinical course and treatment of patients who developed
      cataracts were reviewed. RESULTS: In the first year of life, 134 of 173 children
      examined were treated with pyrimethamine, sulfadiazine, and leukovorin, while the
      remaining 39 were not treated. Cataracts occurred in 27 eyes of 20 patients
      (11.6%, 95% confidence interval [7.2%, 17.3%]). Fourteen cataracts were present
      at birth and 13 developed postnatally. Locations of the cataracts included
      anterior polar (three eyes), anterior subcapsular (six eyes), nuclear (five
      eyes), posterior subcapsular (seven eyes), and unknown (six eyes). Thirteen
      cataracts were partial, nine total, and five with unknown complexity. Twelve
      cataracts remained stable, 12 progressed, and progression was not known for 3.
      Five of 27 eyes had cataract surgery, with 2 of these developing glaucoma.
      Sixteen eyes of 11 patients had retinal detachment and cataract. All eyes with
      cataracts had additional ocular lesions. CONCLUSIONS: In the NCCCTS cohort, 11.6%
      of patients were diagnosed with cataracts. There was considerable variability in
      the presentation, morphology, and progression of the cataracts. Associated
      intraocular pathology was an important cause of morbidity.

PMID- 18086434
TI  - Some distinguishable properties between acid-stable and neutral types of alpha
      amylases from acid-producing koji.
AB  - The highly humid climate of Japan facilitates the growth of various molds. Among
      these molds, Aspergillus oryzae is the most important and popular in Japan, and
      has been used as yellow-koji in producing many traditional fermented beverages
      and foods, such as Japanese sake, and soy sauce. Taka-amylase A (TAA), a major
      enzyme produced by the mold, is well known worldwide to be a leading enzyme for
      industrial utilization and academic study, since many extensive studies have been
      carried out with TAA. In southern Kyushu, the other koji's of citric acid
      producing molds have often been used, such as in the production of a traditional
      distilled liquor of shochu. The koji molds black-koji and white-koji produce two
      types of alpha-amylase, namely, acid-stable (AA) and common neutral (NA). The
      latter enzyme is enzymatically and genetically similar to TAA. In this review, we
      investigate AA from three molds, Aspergillus niger, A. kawachii and A. awamori,
      and the yeast Cryptococcus sp. regarding the distinguishable properties between
      AA and NA. (i) The N-terminus amino acid sequences of AA determined by molecular
      cloning started with the sequence of L-S-A-, whereas those of NA started with A-T
      P-. (ii) Most of the full sequences of AA were composed of, besides a core
      catalytic domain, an extra domain of a hinge region and a carbohydrate binding
      domain, which could be responsible for raw-starch-digestibility. The AA from A.
      niger has no exceptionally extra domain, similarly to NA. (iii) Simple methods
      for distinguishing AA from NA using CNP-alpha-G3 and G5 as substrates were
      developed by our group. (iv) The number of subsite in AA on the basis of its
      cleavage pattern of maltooligosaccharides was estimated to be five, which differs
      from that of TAA, 7-9. AA has many advantages in industrial applications, such as
      its acid-stability, thermostability, and raw-starch digesting properties.

PMID- 18086435
TI  - Effect of variation of root post in different layers of tooth: linear vs
      nonlinear finite element stress analysis.
AB  - The objective of this study was to obtain an accurate stress distribution pattern
      on different domains of a post- and core-treated tooth, taking into account the
      nonlinear properties of the periodontal ligament (PDL). Linear stress and
      deformation analysis was carried out using four posts, different in constitution
      and shape. Accurate three-dimensional models of a restored tooth with different
      layers were prepared using CAD modeling software. The study was carried out using
      a cast metal post and core assembly, a glass fiber, a carbon fiber, and a
      titanium post with a composite resin core. For each restoration, parallel,
      tapered and threaded posts were modeled. However, PDL exhibits nonlinear
      properties ensuring a uniform stress distribution in the tooth structure. Hence,
      accurate results could be expected by simulating the model for the nonlinear
      properties of PDL. Owing to computational difficulties, a simplified model was
      prepared in the ANSYS environment and nonlinear stress analysis was carried out.
      The results indicate that for optimum strength, rigidity and flexibility, tapered
      fiber posts with a composite resin core cemented to the root are desirable. Under
      similar loading conditions, in the case of nonlinear analysis, the stresses
      decreased by approximately 25% and the deformation increased by approximately 50%
      as compared with those in case of linear static analysis for an endodontically
      treated maxillary central incisor. Thus, stress distribution within the restored
      tooth and surrounding tissues can be better anticipated by a dentist. From the
      results of this study, the dimensions of a post could be modified, to further
      reduce stress in the oral cavity and thereby reduce the risk of root and post
      fractures.

PMID- 18086436
TI  - Construction of heterotypic cell sheets by magnetic force-based 3-D coculture of
      HepG2 and NIH3T3 cells.
AB  - Heterotypic 3-D coculture is essential to mimic tissues and organs, because cell
      cell interaction between various types of cells is believed to be important for
      the activation of cellular functions. In this study, magnetic force was applied
      to construct a 3-D coculture system of HepG2 and NIH3T3 cells as a model of
      hepatocytes and mesenchymal cells. Magnetite cationic liposomes (MCLs) were used
      to label target cells. NIH3T3 cells labeled with MCLs were seeded onto ultralow
      attachment plates, whose surface is composed of a covalently bound hydrogel layer
      that is hydrophilic and neutrally charged. When a magnet was placed under the
      plate, cells accumulated on the bottom of the well. After a 24-h incubation
      period, the cells formed a multilayered cell sheet, which contained the major
      mesenchymal extracellular matrix (ECM) components (fibronectin and type I
      collagen), suggesting that the use of stromal NIH3T3 cells gave sufficient
      strength to cell sheets. Both NIH3T3 and HepG2 cells were labeled with MCLs, and
      cocultured by two methods: NIH3T3 cell sheets were constructed and HepG2 cells
      were subsequently seeded onto NIH3T3 cell sheets, and then allowed to form
      layered cell sheets by applying magnetic force; or NIH3T3 and HepG2 cells were
      mixed and then allowed to form mixed cell sheets by applying magnetic force.
      These heterotypic multilayered cell sheets were successfully constructed and an
      enhanced albumin secretion by HepG2 cells was observed. These results suggest
      that the new tissue engineering technique using magnetite nanoparticles and
      magnetic force, to which we refer to as magnetic force-based tissue engineering
      (Mag-TE), is a promising approach to construct multilayered cell sheets
      consisting of heterotypic cocultured cells.

PMID- 18086437
TI  - Cloning, sequence analysis, and expression in Escherichia coli of gene encoding N
      Benzyl-3-pyrrolidinol dehydrogenase from Geotrichum capitatum.
AB  - The gene encoding N-benzyl-3-pyrrolidinol dehydrogenase (DDBJ/EMBL/GenBank
      accession no. AB294179), a useful biocatalyst for producing (S)-N-benzyl-3
      pyrrolidinol, was cloned from the genomic DNA of Geotrichum capitatum JCM 3908.
      The gene contained an open reading frame consisting of 1023 nucleotides
      corresponding to 340 amino acid residues. The subunit molecular weight was
      calculated to be 39,000. The predicted amino acid sequence did not have
      significant similarity to those of N-benzyl-3-pyrrolidinone reductases reported
      previously. From 30 mM N-benzyl-3-pyrrolidinone, (S)-N-benzyl-3-pyrrolidinol was
      obtained with a yield >99.9% and an enantiomeric excess >99.9% in 1-h and 2-h
      reactions without NADH addition by the resting cells of Escherichia coli HB 101
      strains harboring the expression plasmids pSG-POBS and pSF-POBS that possess the
      glucose dehydrogenase gene and formate dehydrogenase gene as an NADH-reproducing
      system, respectively, besides the N-benzyl-3-pyrrolidinol dehydrogenase gene. N
      Benzyl-3-pyrrolidinol dehydrogenase activity (0.56 U/mg) was observed in E. coli
      (pSG-POBS), which was 17-fold the specific activity observed in G. capitatum JCM
      3908.

PMID- 18086438
TI  - Autonomously replicating plasmid transforms Sorangium cellulosum So ce90 and
      induces expression of green fluorescent protein.
AB  - A recombinant plasmid, pRP-GFP, harboring the green fluorescent protein (GFP)
      gene from the broad-host-range mobilizable plasmid pRK415 of the RK2 family was
      constructed and transferred by conjugation from Escherichia coli S17-1 to
      Sorangium cellulosum So ce90. The results of Southern blot analysis showed that
      the plasmid replicated autonomously without being integrated into the chromosome
      of the bacterium. In pRP-GFP, gfp was driven by a So ce90 DNA fragment called
      EpoPro, which is an 890-bp DNA segment spanning from -890 to -1 relative to the
      start codon (GTG) of epoA, a gene that encodes EPOS A, which is presumed to be
      involved in the initiation of epothilone biosynthesis. The GFP in the transformed
      S. cellulosum So ce90 was detected by fluorescence microscopy, which suggests
      that the EpoPro fragment had the function of promoter. Because the green
      fluorescent bacilli could be directly observed by fluorescence microscopy, the
      stable expression of GFP was rapid and convenient for conjugation screening in
      addition to the antibiotic resistance genes within the constructed plasmid. This
      is the first report on an exogenous plasmid that can be stably maintained as an
      extrachromosomal element in S. cellulosum.

PMID- 18086439
TI  - Comparisons of growth and biochemical composition between mixed culture of alga
      and yeast and monocultures.
AB  - The alga Isochrysis galbana 8701 and the yeast Ambrosiozyma cicatricosa were mix
      cultivated in the same medium for 7 d to compare their growth performance and
      biochemical composition with those of the same organisms cultured under
      monoculture conditions. The specific growth rates of both species were
      significantly higher (p<0.05) in the mixed culture than in the monocultures
      during the corresponding experimental phases. At the end of experiment, the
      biomass concentration obtained in the mixed culture reached 1.32+/-0.04 g/l of
      dry weight, which was significantly higher (p<0.05) than those obtained in
      monocultures, and the alga I. galbana in the mixed culture dominated the cell
      numbers making up 96.64% of the cells. The biochemical profile of the mixed
      culture is similar to that of the I. galbana monoculture with some variations;
      The percentages of both the fatty acids 14:00 and 18:00 detected in the mixed
      culture were significantly higher (p<0.05) than those detected in the I. galbana
      monoculture, while the content of the fatty acid 18:2(n-6) detected in the mixed
      culture was significantly lower (p<0.05) than that detected in the I. galbana
      monoculture. This study indicates the improved growth performance in mixed
      culture compared with monocultures and the similarities between the biochemical
      compositions of the mixed culture and the I. galbana monoculture.

PMID- 18086440
TI  - Purification and characterization of a dehydrogenase catalyzing conversion of N
      alpha-benzyloxycarbonyl-L-aminoadipic-delta-semialdehyde to N alpha
      benzyloxycarbonyl-L-aminoadipic acid from rhodococcus sp. AIU Z-35-1.
AB  - The enzyme catalyzing conversion of N alpha-benzyloxycarbonyl-L-aminoadipic-delta
      semialdehyde (N alpha-Z-L-AASA) to N alpha-benzyloxycarbonyl-L-aminoadipic acid
      (N alpha-Z-L-AAA) in Rhodococcus sp. AIU Z-35-1 was identified, and its
      characteristics were revealed. This reaction was catalyzed by a dehydrogenase
      with a molecular mass of 59 kDa. The dehydrogenase exhibited enzyme activity on
      not only N alpha-Z-L-AASA but also N alpha-Z-D-AASA and short chain aliphatic
      aldehydes, but not on aromatic aldehydes and alcohols. The apparent Km values for
      N alpha-Z-L-AASA, N alpha-Z-D-AASA and NAD+ were estimated to be 3.8 mM, 14.1 mM
      and 0.16 mM, respectively. The NH2 terminal amino acid sequence of this enzyme
      exhibited a similarity to those of a piperidein-6-carboxylate dehydrogenase from
      Streptomyces clavuligerus and a putative dehydrogenase from Rhodococcus sp. RHA
      1, but not to those of other microbial aldehyde dehydrogenases.

PMID- 18086441
TI  - Production of single-chain variable fragment antibody (scFv) in fed-batch and
      continuous culture of Pichia pastoris by two different methanol feeding methods.
AB  - This study examined the effects of two methods of methanol feeding, DO-stat and
      methanol concentration control, in fed-batch and continuous cultures of Pichia
      pastoris on cell growth and single-chain variable fragment antibody (scFv)
      expression. By maintaining the methanol concentration at 3.9 g l(-1) in fed-batch
      culture, a scFv concentration of 198 mg l(-1) was obtained. In continuous culture
      using both methanol feeding methods, the scFv concentration in the fermentation
      broth increased with a decreasing dilution rate. A maximum scFv concentration of
      810 mg l(-1) at a dilution rate of 0.0094 h(-1) was obtained by maintaining the
      methanol concentration at 3.9 g l(-1). Although the specific methanol consumption
      rate was the same for both methods, the specific productivity of scFv was higher
      in methanol concentration control from 0.0094 to 0.049 h(-1) than it was in DO
      stat control. Therefore, continuous culture with methanol feeding by the
      concentration control method shows promise for the industrial scale production of
      recombinant proteins by Pichia pastoris.

PMID- 18086443
TI  - Purification and characterization of 2-aminoacetophenone reductase of newly
      isolated Burkholderia sp. YT.
AB  - We found that a newly isolated Burkholderia sp. produced (R)-2-amino-1
      phenylethanol from 2-aminoacetophenone, showing the high stereospecificity. NADPH
      dependent 2-aminoacetophenone reductase purified to homogeneity was a dimer with
      a molecular mass of 65,000. The purified enzyme did not reduce acetophenone and 1
      phenyl-1-propanone. The purified enzyme converted 2-aminoacetophenone to only (R)
      2-amino-1-phenylethanol.

PMID- 18086442
TI  - Composting cattle dung wastes by using a hyperthermophilic pre-treatment process:
      characterization by physicochemical and molecular biological analysis.
AB  - To solve malodorous odor problems by ammonia emission in composting of cattle
      dung wastes, we developed an alternative composting method consisting of a
      hyperthrmophilic pre-treatment reactor (HTPRT) (first step) combined with a
      general windrow post-treatment system (WPOT) (second step). In this study,
      physicochemical and microbiological differences in compost materials during the
      HTPRT-WPOT process and a simple windrow composing process (SWC) were
      investigated. The HTPRT-WPOT process removed excess ammonia in the compost
      materials by physical ammonia stripping, and controlled the malodorous ammonia
      emission. The organic matter evolution index showed that the HTPRT-WPOT process
      also contributed to accelerate formation of humic acids in composting.
      Quantitative real-time PCR analyses using Bacterial-, Archaeal- and fungal
      protozoan-specific primer sets showed that small subunit ribosomal RNA (SSU rRNA)
      gene copy numbers differed much between composting materials of these two
      processes. Particularly, the SSU rRNA gene copy of eukaryotic microbes (fungi
      protozoa) in the HTPRT-WPOT process was much higher than in the SWC process. From
      these results, we conclude that the HTPRT-WPOT process has great advantages for
      the control of malodorous odor problems caused by ammonia emission, and for high
      rate of composting evaluated by the humification rate and microbial
      characterization of the composting materials.

PMID- 18086444
TI  - Application of ultra-water-repellent surface to cell culture.
AB  - In this study, we applied an ultra-water-repellent film to cell culture. We
      cultured cells in droplets on the film and fabricated cell aggregates.
      Furthermore, we allocated cells on micropatterned surfaces consisting of ultra
      water-repellent regions and cell culture-treated regions. The results show that
      the material is useful for cell culture.

PMID- 18086445
TI  - Functional analysis of genes encoding putative oxidoreductases in Aspergillus
      oryzae, which are similar to fungal fructosyl-amino acid oxidase.
AB  - We found 11 genes (FAO1-11) encoding putative oxidoreductases in the Aspergillus
      oryzae genome, which are similar to fungal fructosyl-amino acid oxidases. The
      cDNAs corresponding to the genes were cloned and expressed in Escherichia coli.
      rFao2 had fructosyl-amino acid oxidase activity, whereas rFao1 did not show any
      enzyme activity, even though the deduced amino acid sequence of Fao1 is identical
      to that of one of the fructosyl-amino acid oxidase isozymes from Aspergillus
      oryzae. rFao7 and rFao8 showed oxidase activity toward sarcosine, L-pipecolate,
      and L-proline. rFao10 was active toward only sarcosine, of the substrates tested.
      The functions of the other proteins were also predicted from a phylogenetic
      analysis.

PMID- 18086446
TI  - Synergistic effect of D-glucose and epidermal growth factor display on dynamic
      behaviors of human epithelial cells.
AB  - We investigated the synergistic effect of D-glucose and epidermal growth factor
      (EGF) display on the dynamic cellular behaviors of morphology and migration in a
      culture of human epithelial cells. The time-lapse observation revealed that the
      cells on the D-glucose/EGF-displayed substrate were endowed with enhanced
      migration, accompanied with periodic changes in morphology between round and
      stretched shapes. Immunofluorescence staining of phosphotyrosine PY20 and
      vinculin was conducted to determine the intracellular localization of
      phosphorylated tyrosine expression and focal contact formation, respectively. On
      the substrate displaying D-glucose and EGF, the cells exhibited increases in the
      levels of the expression of phosphorylated tyrosine and the formation of focal
      contacts not only at the cellular periphery but also in the cell body. These
      findings supported the consideration that the displayed D-glucose causes the
      cells to be in close contact with the surface via grasping glucose transporters
      on the cytoplasmic membrane.

PMID- 18086447
TI  - Effect of adding cellulolytic bacterium on stable cellulose-degrading microbial
      community.
AB  - The introduction of an exogenous cellulolytic bacterium into a microbial
      community that was degrading rice straw effectively was evaluated. A stable
      coexistence of the indigenous and exogenous cellulolytic bacteria was achieved by
      adjusting the cultivation conditions. The obtained community required several
      subcultures to reach the highest degradation efficiency.

PMID- 18086448
TI  - Novel technique for fabricating double-layered tubular constructs consisting of
      two vascular cell types in collagen gels used as templates for three-dimensional
      tissues.
AB  - Double-layered tubular constructs consisting of two vascular cell types in
      collagen gels were fabricated using a previously developed technique [Takei et
      al., Biotechnol. Bioeng., 95, 1-7 (2006)]. Histological examination suggested
      that shear stress (4.0 dyn/cm2) on the luminal surface of the constructs induced
      morphological changes in their walls.

PMID- 18086449
TI  - User perceptions of the knowledge underpinning practice orientation dial (KUPOD)
      as a tool to enhance learning.
AB  - The concern of academics and clinicians about the alleged dichotomy between
      theoretical concepts and the practice of nursing has been the catalyst for the
      development of a pocket-sized aid for nurses, known as the Knowledge Underpinning
      Practice Orientation Dial (KUPOD [N]/The Dial). A mixed method approach was used
      incorporating a questionnaire and a focus group of educators. The Dial was
      introduced, as part of a module, undertaken by a cohort of second-year Diploma in
      Nursing (Adult Branch) students. Twenty-eight students returned the questionnaire
      (response rate=85%). Results revealed that the Dial was easy to use in a variety
      of situations and locations. Respondents used the Dial within clinical and
      classroom settings and for self directed study. They reported that it was a
      practical and effective aid to learning, assisting in correlating theory and
      practice. It supported reflection and enhanced confidence in the clinical area,
      indicating that this economically produced tool helps to bridge the theory
      practice gap. The Dial is now being introduced as a learning resource to a wider
      range of students.

PMID- 18086450
TI  - The impact of pre-entry study skills training programmes on students' first year
      experience in health and social care programmes.
AB  - The Faculty of Health and Social Care Sciences at Kingston University and St.
      George's, University of London has provided a pre-entry study skills course since
      July 2001. The course runs over one weekend and although short, is comprehensive.
      An evaluative research study, using case study methodology was undertaken to
      examine the impact of this pre-entry initiative on the first year student
      experience. Data were obtained through focus groups with students and semi
      structured interviews with both students and staff. The findings show that the
      study skills weekend programmes prepare students realistically for their first
      year university experience. In addition, the evaluation helped to develop insight
      into the first year experience which have informed a number of academic
      initiatives.

PMID- 18086451
TI  - Reflections on a study tour to explore history taking and physical assessment
      education.
AB  - In 2005 a study tour, funded by a Florence Nightingale Foundation Travel
      Scholarship, was undertaken by the author to gain insight into the teaching of
      'History Taking and Physical Assessment' (HTPA) across different countries of the
      UK and beyond. The study tour was inspired by recent developments in health
      professional practice, which increasingly require nurses and other health care
      professionals to undertake the skills of history taking, inspection, palpation,
      percussion and auscultation. The study tour visit included 16 Universities across
      the UK, Eire, Canada and the United States. Insights were gained into
      similarities and differences in the content and structure of HTPA courses across
      the centres visited, with valuable observations in respect of mental health
      assessment and optimal session ordering. Insights into modes of delivery
      reinforced perceptions regarding the value of theory, demonstration and small
      group supervised practice, and highlighted interesting issues for debate in
      respect of course text options, videotaped demonstrations, electronic learning
      support programmes and use of mannequins. Consideration of assessment issues
      focused in particular on the value and design of Objective Structured Clinical
      Examination (OSCE) as a core mode of assessment. Wider insights gained in
      relation to HTPA included suggestions of the need for its cautious use in
      preregistration education. There is also debate regarding the teaching of HTPA
      within advanced practitioner preparation. Throughout the report, current and
      planned changes to local practice inspired by the study tour and underpinning
      literature are identified, alongside several recommendations for further
      research.

PMID- 18086452
TI  - Poster presentations: valuing all forms of evidence.
AB  - This paper aims to assist readers who are considering submitting a poster
      presentation to a conference to appreciate their true worth and demonstrate the
      important contribution they can make to nursing scholarship and secondly, to
      provide new insights to conference reviewers who have the task of selecting
      appropriate contributions for conferences. The author will argue that the use of
      poster presentations is an ideal opportunity to disseminate research findings and
      clinical innovations. It offers a new, interesting, and thought-provoking
      perspective on poster presentations, which includes appraisal of extant
      literature and reflections about the significance of poster presentations to
      nursing scholarship. It highlights the benefits of submitting a poster
      presentation and concludes with some key points for conference reviewers to
      consider when deciding to select the suitability of abstracts for poster
      presentations or concurrent sessions.

PMID- 18086453
TI  - 'Back to the bedside': graduate level education in critical care.
AB  - The need for post registration education for nurses practising at specialty level
      in critical care environments is widely acknowledged in nursing and educational
      literature. There is also clear consensus that the ultimate aim of educational
      preparation and practice development is to improve the delivery of nursing care
      to patients who are critically ill and provide support for their families. Yet
      the 'right' approach to educational delivery and evaluation is less clear and
      stimulates considerable debate amongst nursing educators, care providers,
      learners and regulatory bodies. The need for critical care nurses to apply
      advanced knowledge and technical skills to complex and dynamic practice
      situations necessitates the development of critical thinking and a problem
      solving approach to clinical practice that can be fostered through education and
      experience. This paper explores the relationships within teaching, learning and
      practice development in critical care nursing and questions the popular
      assumption that 'post graduate (Master's level) education fits all'. Discussion
      focuses on the successful development and implementation of graduate level
      education for critical care nurses in the South Island of New Zealand and how
      this development is challenging existing approaches to the provision and
      evaluation of formal critical care education in New Zealand.

PMID- 18086454
TI  - The mystery of sudden death: mechanisms for risks.
AB  - This review addresses the possible overlapping mechanisms that may apply to the
      risk of sudden unexpected death occurring in epilepsy and in cardiac disease. It
      explores the interaction between the central and peripheral autonomic nervous
      systems and the cardiopulmonary systems. Included is a discussion of the
      potential interactive role of genetically determined subtle cardiac risk factors
      for arrhythmias with a predisposition for seizure-related cardiac arrhythmias. We
      address the possible mechanisms that are operant in producing both epileptogenic
      and cardiogenic arrhythmias. Finally, we speculate about potential preventive
      measures to minimize the risk of both sudden unexpected death in epilepsy and
      sudden cardiac death.

PMID- 18086455
TI  - Effect of the new antiepileptic drug retigabine in a rodent model of mania.
AB  - Bipolar spectrum disorders are severe chronic mood disorders that are
      characterized by episodes of mania or hypomania and depression. Because patients
      with manic symptoms often experience clinical benefit from treatment with
      anticonvulsant drugs, it was hypothesized that retigabine, a novel compound with
      anticonvulsant efficacy, may also possess antimanic activity. The amphetamine
      (AMPH)+chlordiazepoxide (CDP)-induced hyperactivity model has been proposed as a
      suitable model for studying antimanic-like activity of novel compounds in mice
      and rats. The aims of the present study in rats were therefore (1) to confirm
      previous findings with lithium and lamotrigine, and (2) to evaluate the effect of
      the novel compound retigabine on AMPH+CDP-induced hyperactivity in rats. In all
      experiments, co-administration of AMPH and CDP induced a significant increase
      (191-295%) in locomotor activity. Lithium chloride (0.9 mg/kg) and lamotrigine
      (20 mg/kg), which are known to effectively stabilize mood in humans, both
      significantly decreased AMPH+CDP-induced locomotor activity without affecting
      basal locomotor activity. The results furthermore indicate that retigabine, like
      lithium and lamotrigine, significantly and dose-dependently attenuates the
      induced hyperactivity at a lowest effective dose of 1.0 mg/kg, whereas basal
      locomotor activity is reduced only at doses 4.0 mg/kg. In conclusion, retigabine
      was found to have an antimanic-like effect in the AMPH+CDP-induced hyperactivity
      model, suggesting a potential role for retigabine in the treatment of mania and
      possibly in the management of bipolar disorder.

PMID- 18086456
TI  - Decreased glutamate receptor binding and NMDA R1 gene expression in hippocampus
      of pilocarpine-induced epileptic rats: neuroprotective role of Bacopa monnieri
      extract.
AB  - The potential for antiepileptic drugs to negatively impact cognitive abilities
      has generated renewed interest in herbal drugs and formulations in the treatment
      of epilepsy. Bacopa monnieri is one such widely used revitalizing herb that
      purportedly strengthens nervous function and also possesses memory-enhancing,
      antioxidative, antiepileptic, and anti-inflammatory properties. We investigated
      the neuroprotective role of B. monnieri extract in alteration of glutamate
      receptor binding and gene expression of NMDA R1 in hippocampus of temporal lobe
      epileptic rats. In association with pilocarpine-induced epilepsy, there was
      significant downregulation of NMDA R1 gene expression and glutamate receptor
      binding without any change in its affinity. B. monnieri treatment of epileptic
      rats significantly reversed the expression of NMDA R1 and glutamate receptor
      binding alterations to near-control levels. Also, in the epileptic rats, we
      measured a significant increase in the activity of glutamate dehydrogenase, which
      neared the control level after B. monnieri treatment. The therapeutic effect of
      B. monnieri was also observed in the Morris water maze experiment. These data
      together indicate the neuroprotective role of B. monnieri extract in glutamate
      mediated excitotoxicity during seizures and cognitive damage occurring in
      association with pilocarpine-induced epilepsy.

PMID- 18086457
TI  - Progress in predicting seizure episodes with nonlinear methods.
AB  - One of the most interesting and significant areas of epileptology has been the
      prediction of the onset of a seizure episode from preictal activity with
      nonlinear methods. Not only does this type of study have heuristic value for
      clinical neurophysiology, but it also has potential utilitarian value for the
      patient with seizures. In this review, 47 reports from 12 centers with multiple
      studies are presented in chronological order, as are single reports from 21 other
      centers. The chronological order was chosen to see if progress in the form of
      earlier prediction was made over time. Only 21% of these reports could provide
      specific times for the prediction of seizure onset. The range of values was
      several minutes to 4 hours, with an average (median) of 6-7 minutes. Some reports
      (16%) had negative or nonspecific findings that prediction times could not be
      provided. Thus, only limited progress has been made in predicting a seizure from
      preictal activity, but many other related phenomena have also been studied with
      nonlinear methods with some success.

PMID- 18086458
TI  - Long-term significance of postictal psychotic episodes I. Are they predictive of
      bilateral ictal foci?
AB  - OBJECTIVE: The aim of this study was to determine the degree to which postictal
      psychotic episodes (PIPE) are predictive of bilateral independent ictal foci.
      METHODS: This was a retrospective study of 18 consecutive adults with a partial
      seizure disorder and PIPE (study group) and 36 patients with a partial seizure
      disorder but without PIPE (control group). The two groups were compared with
      respect to the number and location of ictal foci identified with video/EEG
      monitoring, seizure type, etiology, age at seizure onset, duration of seizure
      disorder, MRI abnormalities, and psychiatric history prior to the index video/EEG
      monitoring (other than PIPE). Statistical analyses consisted of logistic
      regression models, one to identify the variables predictive of bilateral ictal
      foci and the other to identify the variables predictive of PIPE. RESULTS: The
      occurrence of PIPE (P<0.0001) and cryptogenic partial epilepsy (P=0.004) was
      predictive of bilateral independent ictal foci in univariate analyses. In
      multivariate analyses, cryptogenic partial epilepsy was the only significant
      variable (P=0.03). Conversely, bilateral independent ictal foci on video/EEG
      monitoring (P<0.0001) and having secondarily generalized tonic-clonic seizures
      (P=0.035) were independent predictors of the development of PIPE in univariate
      and multivariate analyses. Surgery was performed in 20 controls and 3 patients
      with PIPE; 17 controls and 2 patients with PIPE became seizure-free. CONCLUSIONS:
      The presence of PIPE appears to be a predictor of bilateral ictal foci.

PMID- 18086459
TI  - Long-term significance of postictal psychotic episodes II. Are they predictive of
      interictal psychotic episodes?
AB  - OBJECTIVE: The aim of this study was to determine whether postictal psychotic
      episodes (PIPE) are predictive of the development of interictal psychotic
      episodes (IPE). METHODS: This was a retrospective study of 18 consecutive adults
      with a partial seizure disorder and PIPE (study group) and 36 patients with a
      partial seizure disorder but without PIPE (control group). These two groups were
      compared with respect to the likelihood of developing IPE over an 8-year follow
      up period and the variables operant in the development of IPE. Statistical
      analyses consisted of logistic regression models to identify the variables
      predictive of the development of IPE. Predictors included: number and location of
      ictal foci, seizure type, etiology, age at seizure onset, duration of seizure
      disorder, MRI abnormalities, and psychiatric history prior to the index video/EEG
      monitoring (other than PIPE). RESULTS: Seven patients with PIPE and one control
      patient went on to develop an IPE. Predictors of IPE in univariate logistic
      regression analyses included a history of PIPE (P=0.006), male gender (P=0.028),
      and having bilateral ictal foci (P=0.048). Significance disappeared for all of
      these variables when they were entered into a multivariate analysis. CONCLUSIONS:
      A history of PIPE may be a risk factor for the development of IPE. Yet, the
      disappearance of significance on multivariate analysis indicates that it is not
      an independent predictor.

PMID- 18086460
TI  - The Seizures and Epilepsy Education (SEE) program for families of children with
      epilepsy: a preliminary study.
AB  - We investigated the usefulness of the Seizures and Epilepsy Education (SEE)
      program in improving quality of life, management of the seizure condition, and
      health care utilization in families having a child with epilepsy. Members of 15
      families attended the program, with at least one parent from each family
      represented. Children attended if they were at least 12 years of age.
      Participants completed research instruments prior to attending the SEE program,
      and also 1 and 6 months after attendance. Both parents and children reported
      improvement in quality of life relating to child mental health after attending
      the SEE program. Parents reported reduced emotional impact of the child's
      condition, fewer worries, and greater knowledge related to epilepsy. Results
      suggest that attending the SEE program may be beneficial to families having a
      child with epilepsy; however, further study is needed with a more robust research
      design.

PMID- 18086461
TI  - Content analysis of subjective experiences in partial epileptic seizures.
AB  - A new content analysis method for systematically describing the phenomenology of
      subjective experiences in connection with partial epileptic seizures is
      described. Forty patients provided 262 descriptions of subjective experience
      relative to their partial epileptic seizures. The results revealed that
      subjective experiences during seizures consist mostly of sensory and bodily
      sensations, hallucinatory experiences, and thinking. The majority of subjective
      experiences during seizures are bizarre and distorted; nevertheless, the patients
      are able to engage in adequate behavior. To the best of our knowledge, this is
      the first study for which detailed subjective seizure descriptions were collected
      immediately after each seizure and the first study in which the content of verbal
      reports of subjective experiences during seizures, including both the ictal and
      postictal experiences, has been analyzed in detail.

PMID- 18086462
TI  - Psychogenic nonepileptic seizures in patients with learning disability:
      comparison with patients with no learning disability.
AB  - Among a consecutive series of patients with psychogenic nonepileptic seizures
      (PNES), we compared patients with learning disability (LD) (n=25) with patients
      with no LD (n=263), with respect to demographic and clinical variables. A higher
      proportion of the LD group had epilepsy as well as PNES (P<0.001) (uncorrected P
      values are quoted), and a higher proportion were taking antiepileptic drugs at
      the time of diagnosis of PNES (P=0.007). Fewer patients with LD had a history of
      antecedent sexual abuse (P=0.036). A higher proportion of the LD group had
      previous pseudostatus (P<0.001), and a higher proportion had immediate
      situational or emotional triggers for their attacks (P<0.001). There were trends
      toward a higher proportion of men in the LD group (P=0.056) and a longer delay
      between onset of PNES and diagnosis (P=0.072). Our data suggest potentially
      important clinical differences between PNES populations with and without LD, as
      well as possible differences in mechanism.

PMID- 18086463
TI  - A randomized trial of polyunsaturated fatty acids for refractory epilepsy.
AB  - OBJECTIVE: Though polyunsaturated fatty acids (PUFA) reduce seizures in several
      animal models, results have been inconsistent in humans. The goal of the present
      study was to assess the effectiveness of a PUFA supplement as adjunctive
      treatment for intractable focal or generalized epilepsy in humans. METHODS:
      Adults with uncontrolled epilepsy were randomized to either mineral oil placebo
      or a PUFA supplement (eicosapentanoic acid (EPA) plus docosahexanoic acid (DHA),
      2.2 mg/day in a 3:2 ratio). Following a 4-week prospective baseline and 1-week
      titration, subjects entered a 12-week treatment period, followed by an optional 4
      week open-label phase. RESULTS: Of 21 subjects (12 PUFA and 9 placebo), 0 on PUFA
      versus 2 on placebo had at least a 50% decrease in seizure frequency from
      baseline (P=0.17). Overall, seizure frequency increased 6% on PUFA and decreased
      12% on placebo (P=0.21). During optional open-label administration, however, 15
      of 19 subjects had fewer seizures than during baseline (P=0.02). CONCLUSIONS:
      Based on the randomized, blinded portion of this study, the PUFA preparation used
      was not superior to placebo as adjunctive treatment for intractable epilepsy. It
      is not known whether different doses or different EPA:DHA ratios would be
      effective.

PMID- 18086464
TI  - Subungual melanoma: management considerations.
AB  - BACKGROUND: Patients with subungual melanoma (SM) often experience delayed
      diagnosis and present with deep primary lesions. Breslow depth of the primary
      lesion is often unknown before definitive resection, thus complicating treatment
      planning. METHODS: Patients with SM treated at our institution from 1992 to 2004
      were identified from our prospective melanoma database. Clinical and pathologic
      factors were reviewed; Student t test and Kaplan-Meier method were used for
      statistical analysis. RESULTS: Forty-nine patients were identified; most were
      female (63%). The median age was 66 years (range 24 to 83). The most common site
      was the great toe (n = 21), followed by the thumb (n = 15). Eight patients had in
      situ disease; 6 were treated initially with wide local excision, and 4 of these
      eventually required amputation. The median Breslow depth of invasive lesions was
      2.1 mm (range .2 to 11). Toe lesions were thicker than finger lesions (mean 3.5
      vs 2.5 mm, P = .005). Patients with invasive SM of the toe had a less favorable
      outcome than those with finger lesions (5-year overall survival 40% vs 72%,
      respectively; P = .05). Sentinel lymph node (SLN) biopsy was performed in 30
      patients and was positive in 5 (17%); all underwent completion lymphadenectomy.
      Median Breslow depth in patients with positive SLN was 4 mm (range 1.2 to 11).
      Four of 5 patients with positive SLN developed recurrence (median 16 months); 3
      patients died of disease within 40 months. CONCLUSIONS: Patients with SM present
      distinct therapeutic challenges. They continue to present with deep primary
      melanoma, particularly on the toe. Undertreatment of early disease is associated
      with local recurrence.

PMID- 18086465
TI  - Fiber composition of the rat sciatic nerve and its modification during
      regeneration through a sieve electrode.
AB  - Recovery after peripheral nerve transection is seldom complete, the outcome
      depending both on lesion and repair conditions, and on the type and neurochemical
      properties of axons. The interposition between the stumps of a perforated, or
      regenerative electrode (RE) is a promising avenue in the use of chronic nerve
      bioimplants, but represents an additional challenge to regeneration. We applied
      stereological methods to ultrathin and immunostained semithin sections to examine
      quantitatively the axon types that make up the sciatic nerve in control adult
      rats, and their changes 2 months after an RE implant. The number of myelinated
      axons (MAx) increased proximal to RE, but fell to 10% a few millimeters distal.
      This decrease affected more severely motor fibers, characterized by
      immunoreactivity to cholinacetyltransferase (ChAT+), than sensory (ChAT-) fibers.
      Regenerating MAx and myelin sheaths also changed notably in thickness.
      Unmyelinated axons (UAx) showed a moderate reduction in number distal to the
      implant. This reduction affected more tyrosine hydroxylase-immunoreactive axons
      (mostly vaso- and pilomotor fibers), than axons expressing ChAT and/or vasoactive
      intestinal peptide (mostly sudomotor fibers). Taken together with previous
      findings [Negredo, P., Castro, J., Lago, N., Navarro, X., Avendano, C., 2004.
      Differential growth of axons from sensory and motor neurons through a
      regenerative electrode: a stereological, retrograde tracer, and functional study
      in the rat. Neuroscience 128, 605-615.], this study shows that regeneration
      through the RE is much less successful for MAx than UAx, that motor axons
      regenerate more poorly than sensory axons, and that some subclasses of
      sympathetic fibers regenerate better than others. The study also proves the value
      of the combined methodological approach presented here to assess the fiber
      composition of a nerve under normal, pathological or experimental conditions.

PMID- 18086466
TI  - Adrenalectomy counteracts the local modulation of astroglial fibroblast growth
      factor system without interfering with the pattern of 6-OHDA-induced dopamine
      degeneration in regions of the ventral midbrain.
AB  - The present study investigated the effects of bilateral adrenalectomy (ADX) on
      the synthesis of basic fibroblast growth factor (bFGF, FGF-2) mRNA and on the
      expression of its FGF receptor subtype-2 (FGFR2) mRNA after a 6-hydroxydopamine
      (6-OHDA)-induced lesion of nigrostriatal dopamine system. In previous papers we
      have demonstrated that corticosterone increases FGF-2 immunoreactivity mainly in
      the astrocytes of the substantia nigra [Chadi, G., Rosen, L., Cintra, A., Tinner,
      B., Zoli, M., Pettersson, R.F., Fuxe, K., 1993b. Corticosterone increases FGF-2
      (bFGF) immunoreactivity in the substantia nigra of the rat. Neuroreport 4, 783
      786.] and that 6-OHDA injected in the ventral midbrain upregulates FGF-2
      synthesis in reactive astrocytes in the ascending dopamine pathways [Chadi, G.,
      Cao, Y., Pettersson, R.F., Fuxe, K., 1994. Temporal and spatial increase of
      astroglial basic fibroblast growth factor synthesis after 6-hydroxydopamine
      induced degeneration of the nigrostriatal dopamine neurons. Neuroscience 61, 891
      910.]. Rats were adrenalectomized and received a 6-OHDA stereotaxical injection
      in the ventral midbrain 2 days later. Seven days after the dopamine lesion,
      Western blot analysis showed a decreased level of tyrosine hydroxylase in the
      lesioned side of the midbrain, an event that was not altered by ADX or
      corticosterone replacement. Moreover, the degeneration of nigral dopamine
      neurons, which was confirmed by the disappearance of acidic FGF (FGF-1) mRNA and
      the decrement of tyrosine hydroxylase mRNA labeled nigral neurons, was not
      altered by ADX. The FGF-2 protein (23 kDa isoform but not 21 kDa fraction) levels
      increased in the lesioned side of the ventral midbrain. This elevation was
      counteracted by ADX, an effect that was fully reversed by corticosterone
      replacement. In situ hybridization revealed that ADX counteracted the elevated
      FGF-2 mRNA levels in putative glial cells of the ipsilateral pars compacta of the
      substantia nigra and in the ventral tegmental area. The ADX also counteracted the
      increased density and intensity of the astroglial FGF-2 immunoreactive profiles
      within the lesioned pars compacta of the substantia nigra and the ventral
      tegmental area as determined by stereology. The stereotaxical mechanical needle
      insertion triggered the expression of FGFR2 mRNA in putative glial cells,
      spreading to the entire ipsilateral ventral midbrain from the region of needle
      track, an occurrence that was partially reversed by ADX. In conclusion, bilateral
      ADX counteracted the increased astroglial FGF-2 synthesis in the dopamine regions
      of the ventral midbrain following a 6-OHDA-induced local lesion and interfered
      with FGF receptor regulation around injury. These findings give further evidence
      that adrenocortical hormones may regulate the astroglial FGF-2-mediated trophic
      mechanisms and wound repair events in the lesioned central nervous system.

PMID- 18086467
TI  - The differential effects of emotional or physical stress on pain behaviors or on
      c-Fos immunoreactivity in paraventricular nucleus or arcuate nucleus.
AB  - Although many studies which explore on the interaction between stress and
      antinociception have been conducted, most of them do not divide stress into
      emotional stress (ES) and physical stress (PS). In the present study, we
      investigated the differential effects of ES or PS on pain behaviors or on c-Fos
      immunoreactivity (IR) in the paraventricular nucleus (PVN) or arcuate nucleus
      (ArcN) using electrical footshock-witness model. In addition, alteration of pain
      behaviors or c-Fos IR following stress repetition was examined. The electrical
      foot shock was applied to PS animal group in one chamber, whereas the witness
      animal group in another chamber without any electrical foot shock was regarded as
      an ES. In each group, either single (10 stimuli /10 min/1 day) or repeated stress
      for 5 consecutive days was applied. Our results suggest that ES and PS appear to
      play differential roles in the regulation of nociception produced by various
      types of pain stimuli (formalin, substance P, glutamate or pro-inflammatory
      cytokines) and on c-Fos IR in the PVN or ArcN. Moreover, such antinociceptive
      effect or c-Fos IR appears to be modified following stress repetition.

PMID- 18086468
TI  - Evaluation of taurine as a biomarker of liver damage in paracetamol poisoning.
AB  - Taurine is one of the most abundant amino acids in the body. Plasma taurine
      levels of 217 paracetamol positive and 100 paracetamol negative poisoned patients
      (related to non-hepatotoxic agents) referred to the Toxicology lab in Cardiff
      Poisons unit and 90 healthy humans (age between 18 and 45) were measured by a
      high performance liquid chromatography method. The data were analysed using
      linear regression and two-tailed unpaired student t-test using Prism software
      package. We showed that the mean plasma taurine concentration in the paracetamol
      poisoned patients (mean 26.4+/-1.6 mg/l) was significantly different from the
      control groups (mean 5.6+/-0.2 mg/l) (P<0.0001) and the non-paracetamol group
      (mean 18.1+/-1.1 mg/l) (P<0.01). Taurine is produced by the liver in response to
      a toxic insult and subsequent leakage from damaged cells leads to increased
      concentrations in plasma and urine. Therefore a plasma or urinary taurine
      concentration could be a useful marker for paracetamol-induced hepatic damage.

PMID- 18086469
TI  - Osteoclast size heterogeneity in rat long bones is associated with differences in
      adhesive ligand specificity.
AB  - Prothrombin (PT) is an RGD-containing bone-residing precursor to the serine
      protease thrombin (TH), which acts as an agonist for a variety of cellular
      responses in osteoblasts and osteoclasts. We show here that PT, TH, osteopontin
      (OPN) and fibronectin (FN) promoted adhesion of isolated neonatal rat long bone
      osteoclasts. However, the cells that adhered to PT and TH were smaller in size,
      rounded and contained 3-4 nuclei, in comparison to the cells adhering to OPN and
      FN, which were larger with extended cytoplasmic processes and 6-7 nuclei.
      Attachment of the larger osteoclasts to OPN and FN was inhibited by antibodies
      towards beta 3 and beta 1 integrin subunits, respectively. Whereas an RGD
      containing peptide inhibited adhesion of the smaller osteoclasts to PT and TH,
      this was not seen with the beta 3 or beta 1 antibodies. In contrast, the beta 1
      antibody augmented osteoclast adhesion to PT and TH in an RGD-dependent manner.
      Small osteoclasts were less efficient in resorbing mineralized bovine bone
      slices, as well as expressed lower mRNA levels of MMP-9 and the cathepsins K and
      L compared to large osteoclasts. The small osteoclast adhering to PT and TH may
      represent either an immature, less functional precursor to the large osteoclast
      or alternatively constitute a distinct osteoclast population with a specific role
      in bone.

PMID- 18086470
TI  - Morphological and quantitative aspects of nodule formation in hemolymph of the
      blowfly Chrysomya megacephala (Fabricius, 1794).
AB  - Insects manifest effective immune responses that include both cellular and
      humoral components. Morphological and quantitative aspects of cellular and
      humoral cooperation during nodule formation in Chrysomya megacephala hemolymph
      against Saccharomyces cerevisae yeast cells were demonstrated for the first time.
      The analyses were performed in non-injected larvae (NIL), saline-injected larvae
      (SIL) and yeast-injected larvae (YIL). The hemolymph of injected groups was
      collected 0.5, 1, 2, 4, 12, 24, 36, or 48-h post-injection. Morphological aspects
      of YIL nodulation were investigated using transmission electron microscopy (TEM).
      Quantitative analyses consisted of total (THC) and differential hemocyte counts
      (DHC) in all the groups and total yeast count (TYC) in YIL, which were performed
      in an improved Neubauer chamber. Nodule formation was initiated at approximately
      2-h post-injection. Twelve hours after the injection, TEM revealed the presence
      of an amorphous membrane, at the same time that circulating hemocyte number
      decreased significantly contrasting the increase of yeast number. Our results
      showed the ability of C. megacephala hemolymph to perform humoral encapsulation
      when hemocyte population is insufficient to eliminate the microorganisms,
      warranting consideration in future investigations on the relative roles played by
      cellular and humoral elements of innate immunity of this calliphorid.

PMID- 18086471
TI  - Consistent variation in yolk androgens in the Australian Brush-turkey, a species
      without sibling competition or parental care.
AB  - Maternal hormones are an excellent pathway for the mother to influence offspring
      development, and birds provide exceptional opportunities to study these hormone
      mediated maternal effects. Two dominant hypotheses about the function of yolk
      androgens in avian eggs concern maternal manipulation of sibling competition and
      post hatching paternal care. In megapodes, however, neither sibling competition
      nor post hatching parental care exists. Eggs are incubated by external heat
      sources, and chicks dig themselves out of their underground nest and live
      independently of their parents and their siblings. In this first study on egg
      androgens of such a megapode, the Australian Brush-turkey Alectura lathami, we
      found nevertheless substantial amounts of maternal androgens. Since size of the
      incubation mound, incubation temperature, egg size and laying date greatly vary
      in this species, we analysed variation in testosterone (T), androstenedione (A4)
      and dihydrotestosterone (DHT) in relation to these factors. T concentrations were
      significantly higher in eggs from bigger mounds and laid at greater depth, which
      may compensate via anabolic effects for the longer duration and higher energetic
      requirements of chicks when digging themselves out. T concentrations were higher
      in smaller eggs, and both yolk A4 and T concentrations increased with laying
      date, perhaps as a compensatory measure, while DHT concentrations only varied
      across different mounds. These results indicate that maternal androgens may
      influence offspring development outside the contexts of sibling competition or
      parental care.

PMID- 18086472
TI  - Paracrine role of testicular macrophages in control of Leydig cell activities in
      the wall lizard, Hemidactylus flaviviridis.
AB  - The present in vitro study in wall lizards Hemidactylus flaviviridis demonstrates
      the differential paracrine role of testicular macrophages in regulation of Leydig
      cell activities under normal physiological and inflammatory condition for the
      first time in reptiles. To accomplish the objective, the effect of condition
      media of testicular macrophages incubated in medium alone or with FSH/LPS was
      observed on Leydig cell steroidogenesis and proliferation. Non-activated
      testicular macrophage-conditioned medium (TMCM) increased the testosterone
      production from Leydig cells and the stimulation was more pronounced with FSH
      preactivated TMCM, suggesting the trophic effect of FSH on secretion of
      steroidogenic factor from lizard testicular macrophages. Also, testicular
      macrophage-secreted paracrine factor had additive effect on FSH-induced
      testosterone production, since FSH-activated TMCM that contained both FSH as well
      as FSH-induced testicular macrophage-secreted paracrine factor, stimulated the
      Leydig cell steroidogenesis more potently than FSH alone. In contrast, LPS
      activated TMCM inhibited the testosterone production suggesting the inhibitory
      role for testicular macrophages in control of Leydig cell steroidogenesis under
      inflammatory condition. Like steroidogenesis, the differential effects of TMCM
      were observed on Leydig cell proliferation depending on normal or inflammatory
      condition. Non-activated TMCM increased, while LPS-activated TMCM decreased the
      FSH-induced Leydig cell proliferation. It appears that lizard testicular
      macrophages under inflammatory condition secrete a different paracrine factor
      which instead of stimulating inhibits Leydig cell activities.

PMID- 18086473
TI  - Transient transfection of Echinococcus multilocularis primary cells and complete
      in vitro regeneration of metacestode vesicles.
AB  - A major limitation in studying molecular interactions between parasitic helminths
      and their hosts is the lack of suitable in vitro cultivation systems for helminth
      cells and larvae. Here we present a method for long-term in vitro cultivation of
      larval cells of the tapeworm Echinococcus multilocularis, the causative agent of
      alveolar echinococcosis. Primary cells isolated from cultivated metacestode
      vesicles in vitro showed a morphology typical of Echinococcus germinal cells,
      displayed an Echinococcus-specific gene expression profile and a cestode-like DNA
      content of approximately 300Mbp. When kept under reducing conditions in the
      presence of Echinococcus vesicle fluid, the primary cells could be maintained in
      vitro for several months and proliferated. Most interestingly, upon co
      cultivation with host hepatocytes in a trans-well system, mitotically active
      Echinococcus cells formed cell aggregates that subsequently developed central
      cavities, surrounded by germinal cells. After 4 weeks, the cell aggregates gave
      rise to young metacestode vesicles lacking an outer laminated layer. This layer
      was formed after 6 weeks of cultivation indicating the complete in vitro
      regeneration of metacestode larvae. As an initial step toward the creation of a
      fully transgenic strain, we carried out transient transfection of Echinococcus
      primary cells using plasmids and obtained heterologous expression of a reporter
      gene. Furthermore, we successfully carried out targeted infection of Echinococcus
      cells with the facultatively intracellular bacterium Listeria monocytogenes, a
      DNA delivery system for genetic manipulation of mammalian cells. Taken together,
      the methods presented herein constitute important new tools for molecular
      investigations on host-parasite interactions in alveolar echinococcosis and on
      the roles of totipotent germinal cells in parasite regeneration and metastasis
      formation. Moreover, they enable the development of fully transgenic techniques
      in this group of helminth parasites for the first time.

PMID- 18086474
TI  - Gremlin promotes vascular smooth muscle cell proliferation and migration.
AB  - Recent reports highlight the importance of BMP in the vasculature. We
      investigated the expression pattern and role of the BMP antagonist gremlin in
      VSMC. We detected gremlin mRNA constitutive expression in adult and embryonic rat
      aortic VSMC, and in rat carotids. In vitro analysis demonstrated that angiotensin
      II, TGF-beta1 and PDGF induced significant changes in gremlin mRNA expression.
      Gremlin stable overexpression in A7r5 cells blocked BMP signaling. BMP-induced
      reduction in VSMC DNA synthesis was markedly inhibited by gremlin overexpression.
      In fact, gremlin overexpression increased DNA synthesis and cell counts, and
      accelerated cell cycle progression of VSMC, through mechanisms that include
      p27(kip1) down-regulation. Gremlin also led to marked increments in VSMC
      migration. In addition, gremlin gene silencing promoted a significant blockade on
      cell proliferation and migration. In vivo studies disclosed increased gremlin
      protein expression in the neointima of balloon-injured carotid arteries. In
      summary, the BMP antagonist gremlin is constitutively expressed in the normal
      vasculature. Gremlin induces VSMC proliferation and migration and is
      significantly regulated by growth factors and injury. We postulate that gremlin
      plays a part in the development of pathological phenotypic changes of adult VSMC.

PMID- 18086475
TI  - Gene polymorphism influencing treatment response in psychotic patients in a
      naturalistic setting.
AB  - RATIONALE: Many patients with psychotic symptoms respond poorly to treatment.
      Factors possibly affecting treatment response include the presence of
      polymorphisms in genes coding for various receptor populations, drug-metabolizing
      enzymes or transport proteins. OBJECTIVES: To investigate whether genetic
      polymorphisms could be indicators of treatment response to antipsychotic drugs.
      The genes of interest were the dopamine D2 receptor gene (DRD2), the serotonin 2A
      and 2C receptor genes (HTR2A and HTR2C), the P-glycoprotein gene (ABCB1 or MDR1)
      and the drug-metabolizing cytochrome P450 2D6 gene (CYP2D6). MATERIAL AND
      METHODS: Data for this naturalistic, cross-sectional study of patients requiring
      antipsychotic drugs and attending the Psychosis Outpatient Care clinic in
      Jonkoping, Sweden were obtained from patient interviews, blood samples and
      information from patient files. Blood samples were genotyped for DRD2 Taq1 A,
      Ins/Del and Ser311Cys, HTR2A T102C, HTR2C Cys23Ser, ABCB1 1236C>T, 2677G>T/A,
      3435C>T and genetic variants of CYP2D6. The patients (n=116) were grouped
      according to the CANSEPT method regarding significant social and clinical needs
      and significant side effects. RESULTS: Patients on olanzapine homozygous for
      ABCB1 3435T, had more significant social and clinical needs than others. Patients
      with one or two DRD2 Taq1 A1 alleles had a greater risk of significant side
      effects, particularly if they were male, Caucasian, had a schizophrenic or
      delusional disorder or were taking strong dopamine D2-receptor antagonistic
      drugs. CONCLUSION: If these results are confirmed, patients carrying the DRD2
      Taq1 A1 allele would benefit from using drugs without strong dopamine D2 receptor
      antagonistic properties.

PMID- 18086476
TI  - Cerebrovascular events on awakening, patent foramen ovale and obstructive sleep
      apnea syndrome.
AB  - Patent foramen ovale is a defect in the interatrial septum associated with
      cryptogenic stroke. The presumed mechanism of cryptogenic stroke due to a patent
      foramen ovale is the migration of thrombus from the venous side of the
      circulation to the left atrium with subsequent systematic embolism, called
      paradoxical embolization. Provacative maneuvers and pre-existing cardiopulmonary
      disease can cause elevation in right atrial pressure leading to right-to-left
      shunting through a patent foramen ovale. We report two patients with patent
      foramen ovale waking up with cryptogenic vascular events and found to have an
      obstructive sleep apnea syndrome. During nocturnal sleep, obstructive sleep apnea
      can cause right atrium pressure elevation resulting in right-to-left shunting
      through patent foramen ovale. The possibility of patent foramen ovale and an
      obstructive sleep apnea syndrome may be considered in patients with cryptogenic
      strokes-on-awakening. Further studies are needed to support our observation.

PMID- 18086477
TI  - An environmental perspective on metabolism.
AB  - In principle the knowledge of an organism's metabolic network allows to infer its
      biosynthetic capabilities. Handorf et al. [2005. Expanding metabolic networks:
      scopes of compounds, robustness, and evolution. J. Mol. Evol. 61, 498-512]
      developed a method of network expansion generating the set of all possible
      metabolites that can be produced from a set of compounds, given the structure of
      a metabolic network. Here we investigate the inverse problem: which chemical
      compounds or sets of compounds must be provided as external resources in order to
      sustain the growth or maintenance of an organism, given the structure of its
      metabolic network? Although this problem is highly combinatorial, we show that it
      is possible to calculate locally minimal nutrient sets that can be interpreted in
      terms of resource types. Using these types we predict broad nutritional
      requirements for 447 organisms, providing clues for possible environments from
      the knowledge of their metabolic networks.

PMID- 18086478
TI  - Oscillatory dynamics in evolutionary games are suppressed by heterogeneous
      adaptation rates of players.
AB  - Game dynamics in which three or more strategies are cyclically competitive, as
      represented by the rock-scissors-paper game, have attracted practical and
      theoretical interests. In evolutionary dynamics, cyclic competition results in
      oscillatory dynamics of densities of individual strategists. In finite-size
      populations, it is known that oscillations blow up until all but one strategies
      are eradicated if without mutation. In the present paper, we formalize replicator
      dynamics with players who have different adaptation rates. We show analytically
      and numerically that the heterogeneous adaptation rate suppresses the oscillation
      amplitude. In social dilemma games with cyclically competing strategies and
      homogeneous adaptation rates, altruistic strategies are often relatively weak and
      cannot survive in finite-size populations. In such situations, heterogeneous
      adaptation rates save coexistence of different strategies and hence promote
      altruism. When one strategy dominates the others without cyclic competition, fast
      adaptors earn more than slow adaptors. When not, mixture of fast and slow
      adaptors stabilizes population dynamics, and slow adaptation does not imply
      inefficiency for a player.

PMID- 18086479
TI  - Continuous flushing of contaminants from ballast water tanks.
AB  - The transport of non-indigenous species (NIS) with ship ballast water is a major
      environmental problem. The International Maritime Organisation (IMO) have
      recommended that ballast tanks are flushed through with sea water to remove NIS
      contaminants. The flushing efficiency is studied using mathematical models and a
      scaled experimental model of a ballast tank. The density contrast between the
      ballast water and water used for flushing is important when the Froude number
      Fr(w)=U(w)/sqr rt|g(')|H << 1 (defined in terms of average horizontal flow U(w),
      reduced buoyancy g', and H the vertical dimension in the tank). When denser water
      is used to flush a ballast tank, from below, it efficiently displaces lighter
      ballast water; but flushing through with light water creates a buoyant gravity
      current which effectively short circuits part of the tank. When Fr(w)>>1, the
      density contrast between the ballast water and water used for flushing is not
      important and flushing is controlled by a bulk Peclet number, Pe(w). For Pe(w)<<1
      perfect mixing occurs, while for Pe(w)>>1 displacement flushing occurs.
      Laboratory experiments of flushing were performed using a model two-dimensional
      ballast tank employing dye attenuation to measure the whole concentration field
      and these experiments confirm the essential features of the mathematical models.
      The results of this study are discussed in the context of current IMO flushing
      protocols.

PMID- 18086480
TI  - Inhibition of morphine-induced amnesia in morphine-sensitized mice: involvement
      of dorsal hippocampal GABAergic receptors.
AB  - In the present study, the effects of bilateral injections of the GABAergic
      receptor agents into the dorsal hippocampal CA1 regions (intra-CA1) on morphine
      induced amnesia were examined in morphine sensitized-mice. Pre-training
      subcutaneous (s.c.) administration of morphine (5 mg/kg) suppressed the learning
      of a one-trial passive avoidance task. Amnesia induced by pre-training morphine
      was significantly reversed in mice which had previously received once daily
      injections of morphine (20 and 30 mg/kg, s.c.) for 3 days, which may be due to
      behavioral sensitization. Intra-CA1 injections of GABAA receptor agonist,
      muscimol (0.125, 0.25, 0.5 and 1 microg/mouse) or the GABAB receptor agonist,
      baclofen (1, 1.5 and 2 microg/mouse) prior to injection of morphine (20 mg/kg per
      dayx3 days) decreased the reversion of morphine-induced amnesia in morphine
      sensitized-mice. Daily intra-CA1 injections of muscimol or baclofen plus saline
      for 3 days did not alter memory formation. Furthermore, during development of
      sensitization, the combination of GABAA receptor antagonist, bicuculline (0.25,
      0.5, 1 and 2 microg/mouse) with an ineffective dose of morphine (5 mg/kg, s.c.)
      reversed the amnesia induced by pre-training morphine. However, the same
      treatment with GABAB receptor antagonist, CGP35348 (2.5-40 microg/mouse) had no
      effect on the morphine response. On the other hand, daily intra-CA1 injections of
      bicuculline or CGP35348 alone for 3 days did not alter the amnesia induced by pre
      training injection of morphine. The results suggest that morphine sensitization
      reverses the impairment of memory induced by morphine and that GABAergic
      receptors of the dorsal hippocampus may play an important role in this effect.

PMID- 18086481
TI  - Constituents of the stem bark of Discopodium penninervium and their LTB4 and COX
      1 and -2 inhibitory activities.
AB  - The stem bark of Discopodium penninervium afforded a withanolide, 6alpha,7alpha
      epoxy-1-oxo-5alpha,12alpha,17alpha-trihydroxywitha-2,24-dienolide (1) and a
      coloratane sesquiterpene, 7alpha,11alpha-dihydroxy-4(13),8-coloratadien-12,11
      olide (4) along with five known compounds, withanone (2), 5alpha,17beta-dihydroxy
      6alpha,7alpha-epoxy-1-oxowitha-2,24-dienolide (3), 7alpha,11alpha-dihydroxy-8
      drimen-12,11-olide (5), withasomnine (6), and (E,Z)-9-hydroxyoctadeca-10,12
      dienoic acid (7). The identity of the compounds was established on the basis of
      spectroscopic data analysis. All compounds were assessed for inhibition of
      leukotriene metabolism in an in vitro bioassay using activated human neutrophile
      granulocytes, and for in vitro cycloxygenase-1 and -2 inhibition from sheep
      cotyledons and seminal vesicles, respectively. In the leukotriene biosynthesis
      assay all compounds tested at a concentration of 50 microM exhibited activity
      with percentage inhibitions ranging from 11.5 to 36.6. The withanolide, 1,
      displayed a 46.4% inhibition of COX-2 and a 22.9% inhibition of LTB(4) formation
      at 50 microM concentration. Compounds 4 and 6 inhibited LTB(4) biosynthesis but
      showed minor inhibition of COX-1 and COX-2. The remaining compounds, on the other
      hand, were found to be inactive on COX enzymes.

PMID- 18086482
TI  - Aldosterone plasma concentration in horses with heart valve insufficiencies.
AB  - In humans and small animals, heart disease can lead to an increase in
      aldosterone, and the aldosterone level correlates with the severity of the heart
      disease. In horses similar interactions may be possible and may lead to an
      increase in aldosterone in horses with heart valve insufficiencies. In a
      prospective clinical trial eight healthy horses (control group) and 40 horses
      with heart valve disease were examined. In all horses, a clinical (auscultation),
      electro- and echocardiographic examination was performed and aldosterone plasma
      concentration was determined. The median aldosterone plasma concentration in the
      control group was 23.95 pg/ml. Twenty-one out of 40 horses with heart valve
      insufficiencies and without dimensional changes by echocardiography (group 1)
      showed a median aldosterone plasma concentration of 45.5 pg/ml. Five out of the
      40 horses had a left atrial (LA) dilation and an average LA size with 147.6+/-11
      mm (group 2) and a median aldosterone plasma concentration of 95.9 pg/ml. Five
      other horses had a left ventricular (LV) dilation with an average LV size of
      141.6+/-6.8 mm (group 3) and a median aldosterone plasma concentration of about
      115.3 pg/ml. In this group a positive correlation between aldosterone plasma
      concentration and LV existed (r=0.9, P=0.03). Nine horses with both LA (152.8+/
      11.4 mm) and LV dilatation (145+/-9 mm, group 4) had a median aldosterone plasma
      concentration of 161.2 pg/ml. Significant differences of the aldosterone
      concentrations were observed between the control group and the horses with LA and
      LV dilation (group 4, P=0.0005), as well as between group 1 (horses with heart
      valve insufficiency but without dilation) and group 4 (P=0.0006). The study
      confirms that, as reported for other species, aldosterone rises as the severity
      of valvular disease increases. However, in this study, as there is only
      significant difference from normal in the most affected group, it will require
      further study before the plasma aldosterone level can be relied on as an
      indicator of the severity of heart disease in an individual horse.

PMID- 18086484
TI  - Derivation of infectious HIV-1 molecular clones with LTR mutations: sensitivity
      to the CD8+ cell noncytotoxic anti-HIV response.
AB  - CD8(+) cells from healthy, asymptomatic HIV-1-infected individuals can inhibit
      HIV-1 replication in naturally or acutely infected CD4(+) cells in the absence of
      cell killing. This CD8(+) cell noncytotoxic anti-HIV response (CNAR) is mediated
      by a soluble CD8(+) cell antiviral factor (CAF). CNAR/CAF inhibits HIV-1
      replication by blocking viral RNA transcription. HIV transcription is regulated
      by a variety of cis-acting DNA sequence elements within the proviral long
      terminal repeat (LTR). We hypothesized that one of the HIV-1 LTR proviral DNA
      sequence elements that binds host cell transcriptional factors is involved in
      this antiviral activity. To assess this possibility, we constructed full-length
      infectious HIV-1 molecular clones with mutations in the LTR elements NFAT, AP-1,
      IL-2 homology region, and the downstream ISRE. We also tested full-length
      infectious molecular clones that had deletions of either the NF-kappaB or Sp1
      sites of the LTR or lacked functional Tat and TAR elements. Viruses generated
      from these molecular clones were used to acutely infect CD4(+) cells that
      subsequently were either co-cultured with CD8(+) cells from individuals that
      exhibited strong CNAR or cultured with CAF-containing fluids. The replication of
      all of the mutant HIV-1 viruses tested was substantially reduced in the presence
      of CNAR/CAF. These findings suggest that other regions in the viral LTR or other
      host cell processes are involved in the transcriptional block elicited by
      CNAR/CAF.

PMID- 18086483
TI  - Biomarkers of oxidative stress and DNA damage in agricultural workers: a pilot
      study.
AB  - Oxidative stress and DNA damage have been proposed as mechanisms linking
      pesticide exposure to health effects such as cancer and neurological diseases. A
      study of pesticide applicators and farmworkers was conducted to examine the
      relationship between organophosphate pesticide exposure and biomarkers of
      oxidative stress and DNA damage. Urine samples were analyzed for OP metabolites
      and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Lymphocytes were analyzed for
      oxidative DNA repair activity and DNA damage (Comet assay), and serum was
      analyzed for lipid peroxides (i.e., malondialdehyde, MDA). Cellular damage in
      agricultural workers was validated using lymphocyte cell cultures. Urinary OP
      metabolites were significantly higher in farmworkers and applicators (p<0.001)
      when compared to controls. 8-OH-dG levels were 8.5 times and 2.3 times higher in
      farmworkers or applicators (respectively) than in controls. Serum MDA levels were
      4.9 times and 24 times higher in farmworkers or applicators (respectively) than
      in controls. DNA damage (Comet assay) and oxidative DNA repair were significantly
      greater in lymphocytes from applicators and farmworkers when compared with
      controls. Markers of oxidative stress (i.e., increased reactive oxygen species
      and reduced glutathione levels) and DNA damage were also observed in lymphocyte
      cell cultures treated with an OP. The findings from these in vivo and in vitro
      studies indicate that organophosphate pesticides induce oxidative stress and DNA
      damage in agricultural workers. These biomarkers may be useful for increasing our
      understanding of the link between pesticides and a number of health effects.

PMID- 18086485
TI  - Stratification in the cohesion of biofilms grown under various environmental
      conditions.
AB  - The objective of this study was to use indirect methods to assess the biofilm
      cohesion and its vertical stratification. Biofilms were grown under low
      hydrodynamic strengths in two reactors, a low shear stress reactor (LSSR) or
      under a defined shear stress in a Couette-Taylor Reactor (CTR), using different
      electron donors and acceptors. The stratification of biofilm cohesion was
      characterized from a gradual increase of the hydrodynamic strengths in terms of
      shear stress (erosion) and abrasion (collisions of particles). Whatever the
      nature of the biofilms, erosion tests demonstrated a gradual impact of a wall
      shear stress increase on the biofilms remaining on the substratum surface. These
      observations demonstrated that the biofilm cohesion was heterogeneous and
      increased with the biofilm depth. Both erosion and abrasion tests highlighted a
      basal zone of high cohesion. Investigations based on PCR-SCCP and oxygen uptake
      rate showed the presence of active microorganisms in this zone.

PMID- 18086486
TI  - Remediating explosive-contaminated groundwater by in situ redox manipulation
      (ISRM) of aquifer sediments.
AB  - In situ chemical reduction of clays and iron oxides in subsurface environments is
      an emerging technology for treatment of contaminated groundwater. Our objective
      was to determine the efficacy of dithionite-reduced sediments from the perched
      Pantex Aquifer (Amarillo, TX) to abiotically degrade the explosives RDX
      (hexahydro-1,3,5-trinitro-1,3,5-triazine), HMX (octahydro-1,3,5,7-tetranitro
      1,3,5,7-tetrazocine), and TNT (2,4,6-trinitrotoluene). The effects of
      dithionite/buffer concentrations, sediments-solution ratios, and the contribution
      of Fe(II) were evaluated in batch experiments. Results showed that reduced Pantex
      sediments were highly effective in degrading all three high explosives.
      Degradation rates increased with increasing dithionite/buffer concentrations and
      soil to solution ratios (1:80-1:10 w/v). When Fe(II) was partially removed from
      the reduced sediments by washing (citrate-bicarbonate buffer), RDX degradation
      slowed, but degradation efficiency could be restored by adding Fe(II) back to the
      treated sediments and maintaining an alkaline pH. These data support in situ
      redox manipulation as a remedial option for treating explosive-contaminated
      groundwater at the Pantex site.

PMID- 18086487
TI  - Use of stable nitrogen isotope fractionation to estimate denitrification in small
      constructed wetlands treating agricultural runoff.
AB  - Constructed wetlands (CWs) in the agricultural landscape reduce non-point source
      pollution through removal of nutrients and particles. The objective of this study
      was to evaluate if measurements of natural abundance of (15)NO(3)(-) can be used
      to determine the fate of NO(3)(-) in different types of small CWs treating
      agricultural runoff. Nitrogen removal was studied in wetland trenches filled with
      different filter materials (T1--sand and gravel; T3--mixture of peat, shell sand
      and light-weight aggregates; T8--barley straw) and a trench formed as a shallow
      pond (T4). The removal was highest during summer and lowest during autumn and
      winter. Trench T8 had the highest N removal during summer. Measurements of the
      natural abundance of (15)N in NO(3)(-) showed that denitrification was not
      significant during autumn/winter, while it was present in all trenches during
      summer, but only important for nitrogen removal in trench T8. The (15)N
      enrichment factors of NO(3)(-) in this study ranged from -2.5 to -5.9 per
      thousand (T3 and T8, summer), thus smaller than enrichment factors found in
      laboratory tests of isotope discrimination in denitrification, but similar to
      factors found for denitrification in groundwater and a large CW. The low
      enrichment factors compared to laboratory studies was attributed to assimilation
      in plants/microbes as well as diffusion effect. Based on a modified version of
      the method presented by Lund et al. [Lund LJ, Horne AJ, Williams AE, Estimating
      denitrification in a large constructed wetland using stable nitrogen isotope
      ratios. Ecol Engineer 2000; 14: 67-76], denitrification and assimilation were
      estimated to account for 53 to 99 and 1 to 47%, respectively, of the total N
      removal during summer. This method is, however, based on a number of assumptions,
      and there is thus a need for a better knowledge of the effect of plant uptake,
      microbial assimilation as well as nitrification on N isotopic fractionation
      before this method can be used to evaluate the contribution of dinitrification in
      CWs.

PMID- 18086488
TI  - Metal uptake by corn grown on media treated with particle-size fractionated
      biosolids.
AB  - Particle-size of biosolids may affect plant uptake of heavy metals when the
      biosolids are land applied. In this study, corn (Zea mays L.) was grown on sand
      media treated with biosolids to study how particle-size of biosolids affected the
      plant uptake of cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb),
      and zinc (Zn). Two biosolids, the Nu-Earth biosolids and the Los Angeles
      biosolids, of dissimilar surface morphology were utilized. The former exhibited a
      porous and spongy structure and had considerably greater specific surface area
      than that of the latter, which was granular and blocky. The specific surface area
      of the Los Angeles biosolids was inversely proportional to its particle-size,
      while that of Nu-Earth biosolids did not change significantly with particle-size.
      For each biosolid, the metal concentrations were not affected by particle sizes.
      The biomass yields of plants grown on the treated media increased as the biosolid
      particle-size decreased, indicating that plant uptake of nutrients from biosolids
      was dependent on interactions at the root-biosolids interface. The effect of
      particle-size on a metal's availability to plants was element-specific. The
      uptake rate of Cd, Zn, Cu, and Ni was correlated with the surface area of the
      particles, i.e., smaller particles having higher specific area provided greater
      root-biosolids contact and resulted in enhanced uptake of Cd and Zn and slightly
      less increased uptake of Cu and Ni. The particle morphology of biosolids had
      limited influence on the plant tissue concentrations of Cr and Pb. For both types
      of biosolids, total metal uptake increased as biosolid particle-size decreased.
      Our research indicates that biosolid particle-size distribution plays a deciding
      role in plant uptake of heavy metals when they are land applied.

PMID- 18086489
TI  - The contribution of glomalin-related soil protein to Pb and Zn sequestration in
      polluted soil.
AB  - The distribution of lead and zinc in glomalin-related soil protein (GRSP), a
      widespread glycoprotein presumably produced by arbuscular mycorrhizal fungi (AMF)
      in soil, and in some other soil fractions (soil organic matter - [SOM],
      carbonates, phosphates, etc.) was studied in soils from an area near a lead
      smelter that differed in SOM, carbonates and heavy metal (HM) content. Total GRSP
      represented 5.4-21.2% of the SOM and was positively correlated with the soil Pb
      and Zn concentrations (r=0.57 and 0.66, p=0.007 and p=0.001 for Pb and Zn,
      respectively). Pb and Zn were predominantly bound to carbonates and organic
      matter. The amount of lead bound to GRSP varied between 0.69 and 23.4 mg g(-1) DW
      GRSP which is 0.8-15.5% of the total soil Pb. The amount of GRSP-bound metal was
      positively correlated with the total concentration in the case of Pb (r=0.90,
      p=0.000) but the opposite was found for Zn (r=-0.41, p=0.048), indicating that
      GRSP predominantly binds Pb. The percentages of HM-GRSP in HM-SOM were variable
      and were not correlated with SOM content.

PMID- 18086490
TI  - Nicotine place preference in a biased conditioned place preference design.
AB  - Conditioned place preference (CPP) is often more effectively produced with
      nicotine using a biased procedure. Interpretation of results can be problematic,
      however, given that doses that produce CPP in rats have acute anxiolytic and
      residual anxiogenic effects. We tested three groups of male rats in a biased, 2
      chambered apparatus. Over eight conditioning days, one group (paired group)
      received four alternating injections of nicotine paired with the non-preferred
      (white) chamber and of saline in the preferred (black) chamber. A second group
      (counterbalanced group) received two nicotine injections each paired with the
      black and white chambers, with saline pairings on alternate days. A third group
      (saline control) received saline injections paired with both chambers. Following
      conditioning, the paired group spent significantly more time in the initially non
      preferred chamber relative to saline-treated controls, suggesting CPP. The
      counterbalanced group did not show a significant preference shift, providing
      evidence that the observed preference shift in the paired group was not due to a
      drug-induced unconditioned reduction in aversion. Although this finding is
      consistent with the notion that nicotine produced CPP through its rewarding
      effects, we cannot discount the possibility of a conditioned reduction in
      aversion to the non-preferred chamber. For the paired group, a negative
      correlation was found between time spent in the white chamber before conditioning
      and preference shift following conditioning, suggesting that animals showing
      greater initial aversion to a non-preferred context are more likely to form CPP.

PMID- 18086491
TI  - Targeting Fel d 1 to FcgammaRI induces a novel variation of the T(H)2 response in
      subjects with cat allergy.
AB  - BACKGROUND: Induction of CD4+ T cells that produce IL-10 or IFN-gamma is central
      to the protective effects of conventional allergen immunotherapy. OBJECTIVE: We
      examined the T-cell modulatory capacity of a fusion protein (H22-Fel d 1) that
      targets Fel d 1 to the high-affinity IgG receptor (FcgammaRI) on antigen
      presenting cells. METHODS: Monocyte-derived dendritic cells pulsed with H22-Fel d
      1 were analyzed for surface phenotype and cytokine secretion by flow cytometry
      and cytometric bead assay, respectively. CD4+ T cells generated after coculture
      with H22-Fel d 1-pulsed dendritic cells were analyzed at the single-cell level by
      flow cytometry after intracellular cytokine staining. The T-cell repertoire was
      compared for subjects with (IgE+) and without cat allergy (IgE(neg)IgG(neg)),
      including subjects with a modified T(H)2 response (IgE(neg)IgG+). RESULTS: H22
      Fel d 1 induced a semimature phenotype in dendritic cells in conjunction with a
      selective increase in IL-5+ and IL-10+ CD4+ T cells compared with nonreceptor
      targeted Fel d 1. Amplified T cells included diverse subtypes characteristic of
      T(H)0 (IL-5+IFN-gamma+), regulatory T(H)1 (IL-10+IFN-gamma+) and regulatory T(H)2
      (IL-10+IL-5+ cells. T-cell qualitative changes were restricted to subjects with
      allergy and were distinct from a modified T(H)2 response. Blocking IL-10 induced
      by H22-Fel d 1 selectively increased IL-5+ CD4+ T cells, suggesting that T(H)2
      responses were controlled. CONCLUSION: Targeting Fel d 1 to FcgammaRI induces a
      novel variation of the T(H)2 response that incorporates major elements of a
      protective T-cell response.

PMID- 18086492
TI  - "Accentuate the negative, eliminate the positive": engineering allergy
      therapeutics to block allergic reactivity through negative signaling.
AB  - By targeting the dominant-negative signaling receptor FcgammaRIIb expressed on
      proallergic cells, we have developed 2 novel platforms for the treatment of IgE
      mediated allergic disease. First is a genetically engineered bifunctional human
      fusion protein GE2, which is comprised of the Fc portions of human IgE and IgG1
      with an interposed flexible linker designed as a long-term parenteral allergen
      nonspecific therapy. GE2 blocks the effector phase of the IgE response in vitro
      in mice and human subjects and in vivo in the skin and airway and systemically in
      mice and monkeys. Whether reactivity against human GE2 in human subjects will
      limit its applicability remains to be determined. The second platform is designed
      to provide a safer form of allergen-specific immunotherapy and consists of
      genetically engineered chimeric human Fcgamma-allergen proteins, with Fcgamma-Fel
      d 1 as the prototype. The allergen portion binds to specific IgE on FcepsilonRs,
      whereas the Fcgamma portion coaggregates inhibitory FcgammaRIIb and drives
      inhibition of allergic reactivity. Fcgamma-Fel d 1 blocked human mast cell Fel d
      1-induced allergic reactivity in vitro and in vivo in murine models while
      functioning as an immunogen but not as an allergen.

PMID- 18086493
TI  - Rapid corticosteroid effect on beta(2)-adrenergic airway and airway vascular
      reactivity in patients with mild asthma.
AB  - BACKGROUND: Long-term glucocorticoid therapy has been suggested to improve airway
      and airway vascular smooth muscle responsiveness to inhaled beta(2)-agonists in
      patients with asthma. OBJECTIVE: We sought to assess whether a single dose of an
      inhaled glucocorticoid acutely potentiates beta(2)-adrenergic airway and airway
      vascular smooth muscle reactivity in asthma. METHODS: In 10 asthmatic and 10
      healthy subjects, airway blood flow and FEV(1) were measured before and 30
      minutes after fluticasone or placebo inhalation and 15 minutes after the
      subsequent inhalation of racemic albuterol (0.6 mg or 1.25 mg) or (R)-albuterol
      (0.3 mg or 0.6 mg). RESULTS: In healthy subjects all albuterol formulations
      increased airway blood flow equally after placebo or fluticasone pretreatment. In
      asthmatic subjects airway blood flow response was blunted after placebo and
      acutely restored after fluticasone pretreatment. Fluticasone pretreatment did not
      increase FEV(1) responses to any albuterol formulation, except 0.6 mg racemic
      albuterol. CONCLUSION: A single dose of an inhaled glucocorticoid restores
      beta(2)-adrenergic airway vasodilator responses in patients with mild asthma. The
      mechanism of this rapid glucocorticoid effect remains to be clarified.

PMID- 18086494
TI  - Long-term immune reconstitution after anti-CD52-treated or anti-CD34-treated
      hematopoietic stem cell transplantation for severe T-lymphocyte immunodeficiency.
AB  - BACKGROUND: Results of treatment of severe T-lymphocyte immunodeficiencies by
      means of hematopoietic stem cell (HSC) transplantation have improved. T cell
      depleted haploidentical transplantations are successful if there is no HLA
      identical donor. Methods to remove T lymphocytes include addition of anti-CD52
      antibodies and CD34(+) HSC selection. OBJECTIVE: Assessment of long-term immune
      function is important after these treatments. We looked at immune reconstitution
      in 36 survivors for more than 2 years after HSC transplantation for severe T
      lymphocyte immunodeficiencies and compared engraftment quality between the 2 T
      lymphocyte depletion methods. METHODS: Chimerism, T- and B-lymphocyte subsets,
      immunoglobulin levels, and specific antibody production at last follow-up were
      examined. The chi(2) (Fisher exact test) and Wilcoxon rank sum analyses were used
      to compare the groups. RESULTS: Nineteen patients received anti-CD52-treated and
      19 anti-CD34-treated HSCs. More anti-CD52-treated patients had full donor myeloid
      chimerism (P = .025). All patients had full donor T-lymphocyte chimerism. There
      was no difference in donor B-lymphocyte chimerism, but significantly more anti
      CD52-treated patients had class-switched memory B lymphocytes (P = .024), normal
      IgG levels, and normal responses to tetanus and Haemophilus influenzae type B
      vaccination. More anti-CD52-treated patients with common gamma chain or Janus
      associated kinase 3 severe combined immunodeficiency had donor B lymphocytes.
      CONCLUSION: Long-term T-lymphocyte function is good with either treatment method,
      with a low incidence of graft-versus-host disease. The results imply more
      incomplete donor chimerism in anti-CD34-treated patients with less B-lymphocyte
      function.

PMID- 18086495
TI  - Systemic responses after bronchial aspirin challenge in sensitive patients with
      asthma.
AB  - BACKGROUND: In aspirin-sensitive patients with asthma, bronchial obstruction
      induced by oral aspirin may be associated with extrabronchial symptoms,
      suggesting the systemic character of the response. OBJECTIVE: Go assess potential
      systemic effects of local aspirin challenge, hemopoietic progenitors were
      measured in the peripheral blood of challenged patients. METHODS: In 19 patients
      with a history of aspirin-induced asthma, placebo-controlled bronchial challenges
      with lysine-aspirin were performed. Peripheral blood was collected before and
      then 1 hour and 20 hours after challenge (placebo or aspirin). Using the flow
      cytometric method, the numbers of leukocyte (CD34+ cells) and eosinophil
      (CD34+CD125+ cells) progenitors were determined. RESULTS: The challenge was
      positive in 13 patients; 6 patients had isolated local bronchial reaction, and 7
      patients developed systemic symptoms (bronchial and extrabronchial). In patients
      with positive challenge (n = 13), leukocyte progenitors increased significantly
      at 1 hour and 20 hours after challenge (mean, 0.04% at baseline, 0.066% at 1 hour
      after challenge, and 0.073% at 20 hours; P < .05). Eosinophil progenitors raised
      significantly from mean 0.017% before challenge to 0.04% (P < .05) at 20 hours
      after the challenge. At 20 hours after the challenge, the increase in leukocyte
      and eosinophil progenitors was observed only in patients with systemic reactions.
      Positive aspirin challenge was associated with a significant increase in eotaxin
      2 serum concentration. CONCLUSION: This study demonstrated that bronchial
      challenge with aspirin may involve systemic reactions and is associated with
      mobilization of leukocyte and eosinophil progenitor cells from the bone marrow.

PMID- 18086496
TI  - The development of alternative vitrification solutions for microencapsulated
      islets.
AB  - Bioartificial pancreas in which islets of Langerhans (islets) are enclosed in a
      semipermeable membrane is one of the approaches to treat insulin-dependent
      diabetic patients. Although there are advantages in this method, one of the
      issues that still remains is the long-term storage of tissue engineering devices
      before transplantation. One of the possible routes to address this is through
      cryopreservation. In this study, a freezing solution, 2 m DMSO in RPMI-1640, a
      conventional vitrification solution, VS55, and the newly developed vitrification
      solution KYO-1 were examined to cryopreserve microencapsulated islets in agarose
      hydrogel. The insulin release ability, morphology of islets, and physico-chemical
      properties of the agarose gel membrane were examined after a cryopreservation and
      thawing process. Frozen and vitrified (by KYO-1) groups showed a similar insulin
      secretion. Frozen groups by 2 m DMSO, however, showed destruction of agarose
      capsules and some islets were out of the capsule. When KYO-1 was used, islets
      still maintained the ability to release insulin in response to glucose
      stimulation, and agarose capsule showed morphological integrity, and mechanical
      properties. In conclusion, vitrification using KYO-1 which is composed of 5.38 m
      ethylene glycol, 2 m DMSO, 0.1 m PEG 1000 and 0.00175 m PVP K10 in EuroCollins,
      is a suitable method for cryopreservation of microencapsulated islets.

PMID- 18086497
TI  - Expansion of Foxp3-expressing regulatory T cells in vitro by dendritic cells
      modified with polymeric particles carrying a plasmid encoding interleukin-10.
AB  - An emerging focus in experimental gene therapy is to employ non-viral vectors to
      deliver immunosuppressive cytokines aimed at attenuating damaging immune
      responses toward auto and alloantigens. In the current study, we present data
      showing that poly(lactic-co-glycolic acid) (PLGA) particles modified with the
      cationic peptide O10H6 (PLGA(O10H6)) were effective in delivering a mouse IL-10
      encoding plasmid (pIL10) to skew bone marrow-derived dendritic cells (DCs) to
      downregulate T cell responses. T cells stimulated by the IL-10 gene-modified DCs
      exhibited characteristics of regulatory T (Treg) cells, as evident by
      upregulation of Foxp3 transcription factor concomitant with an increase in
      TGFbeta production. Thus PLGA(O10H6) complexed with pIL10 delivers an overriding
      suppressive signal to T cells. Physical characterization of PLGA(O10H6) complexed
      with pIL10 revealed a stable colloidal dispersion. DNA molecules carried by
      PLGA(O10H6) were protected from serum digestion. Collectively, the results raise
      the prospects of using PLGA(O10H6) as a vector for delivering anti-inflammatory
      cytokine genes to modulate T cell responses in vivo.

PMID- 18086498
TI  - Time-on-task, technology and mathematics achievement.
AB  - Information and communication technologies hold much promise for use in education
      in developing countries. This study reports on an evaluation conducted on the
      introduction of computers in the delivery of the mathematics curriculum in one of
      the provinces of South Africa. Although the request was for an outcome evaluation
      very early in the implementation of the program, it was tailored in such a way as
      to fulfill a more formative role. Despite substantial variability in
      implementation, and in most cases with very weak exposure of the learners to the
      intervention, sufficient evidence emerged to indicate that this mode of
      curriculum delivery may be effective. Improvement in mathematics performance was
      related to a range of variables: some concerned classroom teaching practices,
      some referred to social differences between the learners, and some to the
      specific intervention. The strongest of these predictors in the sample was the
      strength of the intervention: the more time learners spent on using the software
      to study mathematics, the more improvement they showed from 1 year to the next in
      their performance in the subject.

PMID- 18086499
TI  - Studies on the reactivity of organometallic Ru-, Rh- and Os-pta complexes with
      DNA model compounds.
AB  - The reactions of arene-metal complexes (arene=p-cymene, benzene or
      pentamethylcyclopentadienyl, metal=Ru, Rh or Os), including 1,3,5-triaza-7
      phosphatricyclo-[3.3.1.1]decanephosphine (pta) and chloro co-ligands, with 9
      methylguanine, adenine, and a series of nucleosides were studied in water to
      ascertain the binding modes. The products were characterized by NMR spectroscopy
      and electrospray ionization mass spectrometry (ESI-MS). Tandem mass spectrometry
      was found to provide excellent information on preferential binding sites. In
      general, the N7 position on guanine (the most basic site) was found to be the
      preferred donor atom for coordination to the metal complexes. The X-ray
      structures of the precursor complexes, [(eta5-C10H15)RhCl(pta-Me)2]Cl2, [(eta6
      C10H14)OsCl(pta)2]Cl, and [(eta6-C6H6)OsCl2(CH3CN)], are also reported.

PMID- 18086500
TI  - Postnatal depression and mother and infant outcomes after infant massage.
AB  - BACKGROUND: Postnatal depression can be a long lasting condition which affects
      both the mother and her baby. A pilot study indicated that attending baby massage
      improved maternal depression and mother-infant interactions. The current study
      further investigates any benefits of baby massage for mothers with postnatal
      depression and their infants. METHODS: Mothers scoring (3)13 on the Edinburgh
      Postnatal Depression Scale (EPDS) at 4 weeks postpartum were randomly assigned to
      attend baby massage classes (n=31) or a support group (n=31). They completed
      depression, anxiety and Infant Characteristics Questionnaires and were filmed
      interacting with their infants before and after 6 intervention sessions, and at
      one year. Thirty four non-depressed mothers also completed the study. RESULTS:
      More of the massage than support group mothers showed a clinical reduction in
      EPDS scores between four weeks and outcome (p<0.05). At one year, massage-group
      mothers had non-depressed levels of sensitivity of interaction with their babies,
      whereas the support group did not. There were no other differences in either
      mother or child between the two intervention groups. Depressed mothers did not
      achieve control depression or anxiety scores at one year. LIMITATIONS: For
      ethical reasons, the study did not include a control group of depressed mothers
      who did not receive an intervention. CONCLUSIONS: Both intervention groups showed
      reductions in depression scores across the study period, but the massage group
      did better on some indices. They also had somewhat better interactions with their
      infants at one year, but these effects were limited.

PMID- 18086501
TI  - Myocardial edema is a feature of Tako-Tsubo cardiomyopathy and is related to the
      severity of systolic dysfunction: insights from T2-weighted cardiovascular
      magnetic resonance.
AB  - We investigated if myocardial edema is a feature of Tako-Tsubo cardiomyopathy
      (TTC). Seven TTC patients in the acute phase were studied using cine, T2 and late
      enhancement cardiovascular magnetic resonance (CMR). A transmural area of high T2
      signal was visible involving the mid-anterior wall and apical segments matching
      the distribution of hypokinesis. CMR-identified edema is a feature of TTC. This
      may provide insight into the pathophysiology of stress-induced cardiomyopathy and
      serve as a useful tool for its non-invasive characterization.

PMID- 18086502
TI  - Effect of the multiple scattering of electrons in Monte Carlo simulation of
      LINACS.
AB  - Results obtained from Monte Carlo simulations of the transport of electrons in
      thin slabs of dense material media and air slabs with different widths are
      analyzed. Various general purpose Monte Carlo codes have been used: PENELOPE,
      GEANT3, GEANT4, EGSNRC, MCNPX. Non-negligible differences between the angular and
      radial distributions after the slabs have been found. The effects of these
      differences on the depth doses measured in water are also discussed.

PMID- 18086503
TI  - Use of nisin-coated plastic films to control Listeria monocytogenes on vacuum
      packaged cold-smoked salmon.
AB  - Cold-smoked (Salmo salar) salmon samples were surface-inoculated with a cocktail
      of three nisin-resistant strains of L. monocytogenes (PSU1, PSU2 and PSU21) to a
      level of approximately 5 x 10(2) or 5 x 10(5) CFU/cm2 of salmon surface. The
      inoculated smoked salmon samples were vacuum-packaged with control film (no
      nisin) or nisin-coated plastic films and stored at either 4 or 10 degrees C. When
      the inoculated smoked salmon samples were packaged with film coated with 2000
      IU/cm2 of nisin, a reduction of 3.9 log CFU/cm2 (compared with control) was
      achieved at either temperature for samples inoculated with 5 x 10(2) CFU/cm(2 of
      L. monocytogenes after 56 (4 degrees C) and 49 (10 degrees C) days of storage
      while reductions of 2.4 and 0.7 log CFU/cm2 were achieved for samples inoculated
      with a high level of L. monocytogenes (5 x 10(5) CFU/cm2) after 58 (4 degrees C)
      and 43 (10 degrees C) days, respectively. For samples packaged in film coated
      with 500 IU/cm2 of nisin, reductions of 0.5 and 1.7 log CFU/cm2 were achieved for
      samples inoculated with a low level of L. monocytogenes (5 x 10(2) CFU/cm2) after
      56 (4 degrees C) and 49 (10 degrees C) days of storage while reductions of 1.8
      and 0.8 log CFU/cm2 were achieved for samples inoculated with high level of L.
      monocytogenes after 58(4 degrees C) and 43 (10 degrees C) days, respectively. In
      addition, nisin inhibited the proliferation of background microbiota on smoked
      salmon in a concentration-dependent manner at both storage temperatures although
      the bacteriostatic effect was more pronounced at refrigeration temperature. This
      work highlights the potential for incorporating nisin into plastic films for
      enhancing the microbial safety of smoked salmon as well as controlling its
      microbial spoilage.

PMID- 18086505
TI  - Cells of origin of small hepatocyte-like progenitor cells in the retrorsine model
      of rat liver injury and regeneration.

PMID- 18086506
TI  - Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty
      liver disease (NAFLD): a cross-sectional study.
AB  - BACKGROUND/AIMS: Low hepatic n-6 and n-3 polyunsaturated fatty acid (PUFA) may
      contribute to steatosis and steatohepatitis and can be affected by diet and
      oxidative stress. METHODS: Seventy-three patients referred for elevated liver
      enzymes and suspected NAFLD were assessed. Nutritional assessment, hepatic FA
      composition and oxidative stress were compared between these groups: simple
      steatosis (SS, n=18), steatohepatitis (NASH, n=38) and minimal findings on liver
      biopsy (MF, n=17). RESULTS: Patients with NASH had higher: BMI, central obesity,
      body fat, insulin resistance, dyslipidemia and lower physical activity compared
      to the other groups. They also had relatively lower hepatic n-3 and n-6 PUFA, a
      decrease in the ratio of metabolites to essential FA precursors for both n-6 and
      n-3 FA (eicosapentaenoic+docosahexaenoic/linolenic and arachidonic/linoleic acid
      ratios) and higher liver lipid peroxides with lower antioxidant power, when
      compared to MF. Overall, there was no significant difference between SS and NASH
      in FA composition. Self-reported dietary intake and red blood cell FA composition
      were similar among the three groups. CONCLUSIONS: NASH patients have more
      metabolic abnormalities. This is associated with higher oxidative stress and
      lower n-3 and n-6 PUFA in the liver in the absence of any differences in dietary
      FA composition.

PMID- 18086507
TI  - Mortality related to chronic hepatitis B and chronic hepatitis C in France:
      evidence for the role of HIV coinfection and alcohol consumption.
AB  - BACKGROUND/AIMS: Mortality related to HCV and HBV infections was estimated in
      France. METHODS: A random sample (n=999) of death certificates was obtained from
      all death certificates listing HBV, HCV, hepatitis, liver disease, possible
      complication of cirrhosis, bacterial infection, HIV, or transplantation
      (n=65,000) in France in 2001. Physicians who reported the deaths were sent a
      questionnaire to identify how many deaths were related to HBV/HCV infection.
      Completed forms were independently analyzed by a panel of hepatologists. Death
      rates were estimated according to national population census data. RESULTS:
      Estimated annual number of deaths associated with HCV and HBV infection was 3618
      and 1507, respectively (6.1 and 2.5 deaths per 100,000 inhabitants,
      respectively). Estimated number of deaths attributable to HCV or HBV infection
      was 2646 and 1327, respectively (4.5 and 2.2 deaths per 100,000 inhabitants,
      respectively). In the HCV infection group, 95 percent had cirrhosis; 33 percent
      had hepatocellular carcinoma (HCC). In the HBV infection group, 93 percent had
      cirrhosis; 35 percent had HCC. Eleven percent of deaths occurred in patients with
      HIV coinfection. Deaths related to HBV or HCV infection occurred at an earlier
      age in patients with a history of excessive alcohol consumption. CONCLUSIONS: In
      France, 4000-5000 deaths related to HCV and HBV infection occurred in 2001.
      Alcohol consumption and HIV infection were important co-factors. These data
      emphasize the need for ongoing, efficient public health programs that include
      screening, management, and counseling for HCV- and HBV-infected individuals.

PMID- 18086508
TI  - Prevalence of malnutrition in paediatric hospital patients.
AB  - BACKGROUND & AIMS: Childhood malnutrition has severe adverse effects on growth
      and development, but only limited information is available on the prevalence of
      malnutrition in paediatric hospital patients. We determined the prevalence of
      malnutrition in a series of unselected patients consecutively admitted as
      inpatients to a large tertiary care children's hospital in Germany. PATIENTS AND
      METHODS: Data for weight and height upon admission were recorded in 475
      unselected children aged 7.9+/-5 years (mean+/-SD). Weight for height 81-90 of
      median values were considered to indicate mild malnutrition, 70-80% moderate
      malnutrition and <70% severe malnutrition according to cut-off points defined by
      Waterlow. RESULTS: Some 24.1% of the patients were malnourished, with 17.7% of
      all patients who were mildly, 4.4% who were moderately and 1.7% who were severely
      malnourished. The largest proportion of malnourished patients was found among
      patients with multiple diagnoses (42.8% malnourished), mental retardation
      (40.0%), infectious diseases (34.5%) and cystic fibrosis (33.3%). CONCLUSIONS:
      The very high prevalence of malnutrition among children admitted to a children's
      hospital is considered intolerable, given the adverse consequences for short- and
      long-term health and well-being. Strategies for systematic screening and
      treatment of malnutrition in paediatric patients need to be refined and
      implemented.

PMID- 18086509
TI  - Women's attitudes and expectations regarding gynaecological examination.
AB  - OBJECTIVE: to describe women's expectations of doctors and nurses during
      gynaecological examination, to identify if women have a preference for the
      doctor's gender, to investigate women's feelings during examination, and to
      determine why women consult the gynaecological outpatient clinic. DESIGN: a
      descriptive and cross-sectional study using a questionnaire administered face to
      face. SETTING: this study was performed with women recruited from those making an
      appointment for gynaecological examination at the gynaecological outpatient
      clinic at Manisa Maternity and Child Hospital between September 2004 and February
      2005. PARTICIPANTS: four hundred and thirty-three women who applied to the
      gynaecological outpatient clinic at Manisa Maternity and Child Hospital.
      MEASUREMENTS: the questionnaire included questions about the women's socio
      demographic and reproductive characteristics, feelings with regard to pelvic
      examination, expectations of doctors and nurses during gynaecological
      examination, preferences regarding the gender of the physician, and the reason
      for the gynaecological examination. FINDINGS: more than one-half of women felt
      anxious or worried about their health situation during the pelvic examination
      (54.8%), and 41.8% of women said that they were embarrassed about having to
      undress. 45.5% of women reported that they would prefer a female doctor, only
      4.2% of women would prefer a male doctor in their obstetric and gynaecological
      care, and the remaining women (49.9%) expressed no preference. Most women (62.1%)
      expected the doctor to explain their health situation after examination. 71.8% of
      women said that the nurse should have an understanding and gentle manner, and
      28.2% of women stated that the nurse should offer information to the patient
      about the pelvic examination. KEY CONCLUSIONS: it was very important for the
      women to participate through receiving information during the gynaecological
      examination. When treated with respect, the women were able to have a positive
      relationship with the staff. This encourages the women to attend clinics for
      their own health needs. Gynaecological examination is an essential part of
      gynaecological care and the most common procedure in gynaecological practice.
      Many women in the world will have a gynaecological examination several times
      during their lives, from youth to old age. This study could contribute to improve
      health programmes to make the gynaecological examination situation more positive
      for women.

PMID- 18086511
TI  - 28-Day oral (gavage) toxicity studies of green tea catechins prepared for
      beverages in rats.
AB  - The beneficial health effects associated with drinking green tea are widely
      considered to be due primarily to tea catechins. Heat treatment of marketed green
      tea beverages for sterilization causes epimerization and/or polymerization of tea
      catechins. Safety studies on heat-treated tea catechins are limited. The
      objective of the present study was to evaluate potential adverse effects, if any,
      of two standardized green tea catechin (GTC) preparations: one that underwent
      heat sterilization (GTC-H) and one that was not heat-sterilized (GTC-UH). A
      decaffeinated preparation of the GTC-H (GTC-HDC) was also evaluated to ascertain
      if any effects were due to caffeine. The GTC preparations were administered to
      rats once daily at levels up to 2000 mg/kg/day for 28 days. There were no deaths
      attributable to the GTC preparations. The clinical condition of the animals,
      functional observational battery, motor activity, clinical pathology evaluations,
      organ weights, and gross necropsy findings were unaffected by any of the GTC
      preparations. GTC-HDC or GTC-UH dosing had no effects on body weights or
      microscopic findings, whereas lower body weights and food consumption were
      observed in the 1000 and 2000 mg/kg/day GTC-H group males. The no observed
      adverse-effect level (NOAEL) for localized gastric effects for GTC-H was 1000
      mg/kg/day. No other target organs were identified. Thus, the NOAEL for systemic
      toxicity following oral administration was 2000 mg/kg/day for GTC-H, GTC HDC, and
      GTC-UH under the conditions of this study.

PMID- 18086510
TI  - Threat of heavy metal pollution in halophytic and mangrove plants of Tamil Nadu,
      India.
AB  - Mangrove and halophytic plants occur along the coastal areas of Tamil Nadu, south
      India and these plants have been used in traditional medicine for centuries.
      Heavy metals are known to pose a potential threat to terrestrial and aquatic
      biota. However, little is known on the toxic levels of heavy metals found in
      mangrove and halophytic plants that are used in traditional medicine in India. To
      understand heavy metal toxicity, we investigated the bioconcentration factors
      (BCF) of heavy metals in leaves collected from eight mangroves and five
      halophytes in the protected Pichavaram mangrove forest reserve in Tamil Nadu
      State, south India. Data presented in this paper describe the impact of essential
      (Cu, Fe, Mg, Mn and Zn) and non-essential/environmentally toxic trace metals (Hg,
      Pb and Sn) in mangrove and halophytic medicinal plants. The concentrations of Pb
      among 13 plant species were higher than the normal range of contamination
      reported for plants. The average concentration of Hg in the halophytic plants
      (0.43+/-0.37 microg/g) was seven times higher than mangrove plants (0.06+/-0.03
      microg/g) and it indicated pollutants from industrial sources affecting
      halophytes more than mangroves.

PMID- 18086512
TI  - Criteria for confirming sequence periodicity identified by Fourier transform
      analysis: application to GCR2, a candidate plant GPCR?
AB  - Methods to determine periodicity in protein sequences are useful for inferring
      function. Fourier transformation is one approach but care is required to ensure
      the periodicity is genuine. Here we have shown that empirically-derived
      statistical tables can be used as a measure of significance. Genuine protein
      sequences data rather than randomly generated sequences were used as the
      statistical backdrop. The method has been applied to G-protein coupled receptor
      (GPCR) sequences, by Fourier transformation of hydrophobicity values, codon
      frequencies and the extent of over-representation of codon pairs; the latter
      being related to translational step times. Genuine periodicity was observed in
      the hydrophobicity whereas the apparent periodicity (as inferred from previously
      reported measures) in the translation step times was not validated statistically.
      GCR2 has recently been proposed as the plant GPCR receptor for the hormone
      abscisic acid. It has homology to the Lanthionine synthetase C-like family of
      proteins, an observation confirmed by fold recognition. Application of the
      Fourier transform algorithm to the GCR2 family revealed strongly predicted seven
      fold periodicity in hydrophobicity, suggesting why GCR2 has been reported to be a
      GPCR, despite negative indications in most transmembrane prediction algorithms.
      The underlying multiple sequence alignment, also required for the Fourier
      transform analysis of periodicity, indicated that the hydrophobic regions around
      the 7 GXXG motifs commence near the C-terminal end of each of the 7 inner helices
      of the alpha-toroid and continue to the N-terminal region of the helix. The
      results clearly explain why GCR2 has been understandably but erroneously
      predicted to be a GPCR.

PMID- 18086513
TI  - How good is GLASOD?
AB  - The Global Assessment of Soil Degradation (GLASOD) has been the most influential
      global appraisal of land quality in terms of environmental policy. However, its
      expert judgments were never tested for their consistency and could not be
      reproduced at unvisited sites, while the relationship between the GLASOD
      assessments of land degradation and the social and economic impact of that
      degradation remains unclear. Yet, other methodologies that could respond to
      urgent calls for an updated assessment of the global environmental quality are
      not operational or, at best, in progress. Therefore, we evaluate the reliability
      and social relevance of the GLASOD approach and assess its candidacy for new
      global environmental assessments. The study concentrates on the African
      continent, capitalizing on new GIS data to delineate and define the
      characteristics of GLASOD map units. Consistency is tested by comparing expert
      judgments on soil degradation hazard for similar combinations of biophysical
      conditions and land use. Reproducibility is evaluated by estimating an ordered
      logit model that relates the qualitative land degradation classes to easily
      available information on explanatory variables, the results of which can be used
      to assess the land degradation at unvisited sites. Finally, a cross-sectional
      analysis investigates the relation between GLASOD assessments and crop production
      data at sub-national scale and its association with the prevalence of
      malnutrition. The GLASOD assessments prove to be only moderately consistent and
      hardly reproducible, while the counter-intuitive trend with crop production
      reveals the complexity of the production-degradation relationship. It appears
      that increasing prevalence of malnutrition coincides with poor agro-productive
      conditions and highly degraded land. The GLASOD approach can be improved by
      resolving the differences in conceptualization among experts and by defining the
      boundaries of the ordered classes in the same units as independent, quantitative
      land degradation data.

PMID- 18086514
TI  - Colombia's discharge fee program: incentives for polluters or regulators?
AB  - Colombia's discharge fee system for water effluents is often held up as a model
      of a well-functioning, economic incentive pollution control program in a
      developing country. Yet few objective evaluations of the program have appeared.
      Based on a variety of primary and secondary data, this paper finds that in its
      first 5 years, the program was beset by a number of serious problems including
      limited implementation in many regions, widespread noncompliance by municipal
      sewerage authorities, and a confused relationship between discharge fees and
      emissions standards. Nevertheless, in some watersheds, pollution loads dropped
      significantly after the program was introduced. While proponents claim the
      incentives that discharge fees created for polluters to cut emissions in a cost
      effective manner were responsible, this paper argues that the incentives they
      created for regulatory authorities to improve permitting, monitoring, and
      enforcement were at least as important.

PMID- 18086515
TI  - Soybean saponin inhibits tumor cell metastasis by modulating expressions of MMP
      2, MMP-9 and TIMP- 2.
AB  - The antimetastatic properties of soybean saponin were investigated by evaluating
      matrix metalloproteinase (MMP-2 and MMP-9) production in HT-1080 cells. The mRNA
      expression levels of MMP-2 and MMP-9 were determined by RT-PCR analysis. The
      levels of secreted MMP-2, MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP
      2) were determined by gelatin zymography and/or ELISA. The invasion of a Matrigel
      coated membrane by human fibrosarcoma HT-1080 and HT-29 colon cancer cells was
      quantitatively assessed by counting the migrated cells. The treatment of HT-1080
      cells with soybean saponin inhibited the mRNA expression of and reduced the
      amounts of secreted MMP-2 and MMP-9, whereas it increased the amount of secreted
      TIMP-2 dose-dependently. Soybean saponin significantly inhibited the invasion of
      HT-1080 cells through a Matrigel-coated membrane. The antimetastatic properties
      by soybean saponin were further confirmed by in vivo mice experiment via the tail
      vein injection of CT-26 colon cancer cells after feeding the mice the dietary
      soybean saponin. The incidence of metastatic tumor colonization of lungs of mice
      moderately decreased 2 weeks after the tail vein injection of CT-26 cells. Our
      current data support the notion that soybean saponin inhibits tumor cell
      metastasis by suppressing MMP-2 and MMP-9 productions, and stimulating TIMP-2
      secretion, thereby suggesting that soybean saponin has a chemopreventive property
      against cancer metastasis.

PMID- 18086516
TI  - Results of a randomized controlled trial to examine the efficacy of a chronic
      pain self-management group for older adults [ISRCTN11899548].
AB  - Chronic pain is a common, disabling problem in older adults. Pain self-management
      training is a multimodal therapy that has been found to be effective in young to
      middle-aged adult samples; however, few studies have examined the effectiveness
      of this therapy in older adults. In this randomized, controlled trial, we
      evaluated a pain self-management training group (SMG) intervention as compared
      with an education-only (BOOK) control condition. Participants, 65 years of age or
      older who experienced persistent, noncancer pain that limited their activities,
      were recruited from 43 retirement communities in the Pacific Northwest of the
      United States. The primary outcome was physical disability, as measured by the
      Roland-Morris Disability Questionnaire. Secondary outcomes were depression
      (Geriatric Depression Scale), pain intensity (Brief Pain Inventory), and pain
      related interference with activities (Brief Pain Inventory). Randomization
      occurred by facility to minimize cross-contamination between groups. Two-hundred
      and fifty-six individuals, mean age=81.8 (SD: 6.5), enrolled and 218 completed
      the study. No significant differences in outcomes were found between groups at
      post-intervention, 6-month follow-up, or 12-month follow-up. The SMG group showed
      a significantly greater increase over time, relative to the BOOK group, in two
      process measures, as measured by the Chronic Pain Coping Inventory: use of
      relaxation and use of exercise/stretching. In both cases, the increase was
      greatest from baseline to the post-intervention assessment. Study findings
      indicate that additional research is needed to determine the most effective
      content and delivery methods for self-management therapies targeted at older
      adults with chronic pain.

PMID- 18086517
TI  - How DMSO, a widely used solvent, affects spinal cord injury.
AB  - The aim of this experimental study was to investigate whether dimethylsulfoxide
      (DMSO) has protective effects on spinal cord ischemia-reperfusion (I/R) injury.
      New Zealand rabbits were enrolled in the study. In addition to the control group,
      the study group received 0.1 mL/kg DMSO prior to ischemia. Blood samples were
      taken to obtain nitrite-nitrate levels during the surgical procedure. After
      neurological evaluation at 24 hr of reperfusion, lumbar spinal cords were removed
      for electron microscopic evaluation and malondialdehyde and myeloperoxidase
      measurements. The mean Tarlov score of the DMSO group was higher than that of the
      control group. Electron microscopic examination was carried out with tissue
      samples at 24 hr of reperfusion. The DMSO group had better preservation with the
      electron microscopic scoring compared to the control group. Malondialdehyde and
      myeloperoxidase levels were decreased in the DMSO group compared to the control
      group. Nitrite-nitrate levels were also lower in the DMSO group compared to
      control at 5 and 30 min of reperfusion. This study demonstrates a considerable
      neuroprotective effect of DMSO on neurological, biochemical, and
      histopathological analyses during periods of spinal cord I/R injury in rabbits.
      Although there was a difference between the DMSO and control groups in all
      measured parameters in our study, this was not statistically significant. DMSO
      deserves further investigation related with spinal cord ischemia and reperfusion.
      We should also consider the effect of DMSO when we use it as a solvent or vehicle
      during experimental I/R models.

PMID- 18086518
TI  - Factors influencing depression endpoints research (FINDER): study design and
      population characteristics.
AB  - Factors influencing outcomes of depression in clinical practice, especially
      health-related quality of life (HRQoL), are poorly understood. The Factors
      Influencing Depression Endpoints Research (FINDER) study is a European
      prospective, observational study designed to estimate the HRQoL of adults with a
      clinically diagnosed depressive episode at baseline, and 3 and 6 months after
      commencing antidepressant medication. We report here the study design and
      baseline patient characteristics. HRQoL was assessed by the 36-item Short-Form
      Health Survey (SF-36) and European Quality of Life-5 Dimensions (EQ-5D). Patient
      ratings on Hospital Anxiety and Depression Scale (HADS) and pain Visual Analogue
      Scale (VAS) were also obtained. Results (n=3468) showed that SF-36 mental
      component summary (mean 22.2) was more than two SDs below general population
      norms (mean 50.0) and one SD below clinical depression norms (mean 34.8); the
      physical component summary (mean 46.1) was similar to general population (mean
      50.0) and clinical depression norms (mean 45.0). Mean EQ-5D scores were also
      lower than general population norms. Mean HADS-Depression and -Anxiety subscores
      were 12.3 and 13.0, respectively. Fifty-six percent of patients reported an
      overall pain VAS score of at least 30mm and 70% of these patients had no physical
      explanation for their pain. Further investigation into factors associated with
      HRQoL in depression after treatment initiation is warranted.

PMID- 18086519
TI  - The cost of moderate and severe COPD exacerbations to the Canadian healthcare
      system.
AB  - BACKGROUND: The cost of exacerbations in chronic obstructive pulmonary disease
      (COPD) has not been well studied. The aim of this study was to identify and
      quantify the (average) cost of moderate and severe exacerbations (ME and SE,
      respectively) from a Canadian perspective. METHODS: Resources used during ME and
      SE were identified in a year long prospective, observational study (Resource
      Utilization Study In COPD (RUSIC)). The units of analysis were ME and SE. Unit
      costs (2006$CAN), based on provincial, hospital and published sources, were
      applied to resources. The overall cost per ME and SE were calculated. The
      population burden of exacerbations was also calculated. RESULTS: Among study
      participants (N=609, aged 68.6+/-9.4 years, 58.3% male) there were 790
      exacerbations: 639 (80.9%) MEs and 151 (19.1%) SEs. Of the 790 exacerbations, 618
      (78.2%), 245 (31.0%) and 151 (19.1%) included a visit to an outpatient clinic,
      emergency department (ED) or hospital, respectively. For ME, 85.9% and 13.1%
      involved visits to GPs and respirologists, respectively. Pharmacologic treatment
      changes in the outpatient setting involved antibiotics (63.1%) and
      corticosteroids (34.7%). The overall mean costs for outpatient and ED services
      for MEs were $126 (N=574) and $515 (N=105), respectively. The average overall
      cost of a ME was $641. For SEs, the average hospital stay was 10.0 days. The
      overall mean costs of outpatient, ED and hospitalization services for SE were
      $114 (N=44), $774 (N=140) and $8669 (N=151), respectively. The average overall
      cost of a SE was $9557. CONCLUSION: The economic burden associated with MEs and
      especially SEs, in Canada, is considerable and likely has a substantial impact on
      healthcare costs. The overall burden of exacerbations has been estimated in the
      range of $646 million to $736 million per annum.

PMID- 18086520
TI  - Imaging of pleural masses: which to choose?
AB  - The differential diagnosis of pleural masses is limited. Asbestos-related disease
      and invasive bronchogenic carcinoma make up the majority of cases. The diagnostic
      yield of biopsies is low, and invasive procedures are often required to achieve
      diagnosis. A variety of imaging techniques are available to help differentiate
      between benign and malignant disease to help discern which patients to biopsy.
      While computed tomography has a relatively good sensitivity and specificity,
      magnetic resonance imaging (MRI) and positron emission tomography (PET) both
      appear to have higher accuracy. MRI has the added benefit of being an excellent
      aid in determining surgical resectability of tumors. MRI and PET are limited,
      however, by their cost and availability in certain regions.

PMID- 18086521
TI  - Broncho-alveolar lavage fluid recovery correlates with airway neutrophilia in
      lung transplant patients.
AB  - Broncho-alveolar lavage (BAL) is important to assess airway inflammation. There
      is debate about the volume instilled, but the variation of BAL fluid recovery
      (BFR) has received little attention. We investigated the association between BFR
      and rejection/infection status after lung transplantation (LTx). We combined
      clinical findings, FEV1, transbronchial biopsies and BAL analysis (BFR,
      interleukin-8 (IL8), cell counts, microbiology) of 115 samples/LTx patients. The
      patients were divided into 4 groups: stable (subdivided in colonized and non
      colonized), acute rejection (AR), Bronchiolitis Obliterans Syndrome (BOS) and
      infection. BFR was significantly lower in AR, BOS and infection, and correlated
      with the severity of AR and BOS. A 10 ml decrease of BFR was associated with a
      FEV1 decrease of 4.4% and a %neutrophils and IL8 increase of 9.6% and 9.7 pg/ml,
      respectively. Colonized stable patients had no significant differences in airway
      inflammation, FEV1 and BFR compared to the non-colonized stable patients. We
      conclude that a low BFR is an indicator of lung rejection or infection. BFR
      variation is related to airway obstruction and neutrophilic inflammation, which
      can cause an increased compliance of the airway wall, making it more collapsible.
      Airway colonization in stable patients had no effect on airway inflammatory
      parameters, BFR and FEV1.

PMID- 18086522
TI  - Bronchiectasis in Central Australia: a young face to an old disease.
AB  - BACKGROUND: Bronchiectasis remains a significant cause of morbidity among
      specific populations world wide, including many indigenous groups. Data on
      prevalence in Australian adults are lacking. Indigenous children in Central
      Australia have the highest rates of bronchiectasis in the world. Outcomes for
      these individuals after they become adults are not currently available. METHODS:
      We performed a retrospective case review of the presentation and likely aetiology
      of adult patients presenting to the Alice Springs Hospital with a primary
      diagnosis of bronchiectasis. RESULTS: Sixty-one patients and 166 admissions were
      identified. Fifty-nine patients were indigenous (97%). Mean age was 42+/-15
      years. Forty-three patients (70%) had past histories notable for recurrent
      respiratory tract infections. No predisposing factors could be identified in 11
      patients (18%). Human T-cell lymphotropic virus type 1 (HTLV-1) serology was
      positive in 72% of those studied. Eight (13%) patients died during the study
      period. CONCLUSION: Bronchiectasis remains a significant cause of morbidity and
      mortality in Central Australia, with notably different patient characteristics
      and disease aetiology to other published cohorts. Recurrent respiratory infection
      is the major cause of illness. Associated factors include indigenous ethnicity,
      HTLV-1 positivity and childhood in a remote region.

PMID- 18086523
TI  - Pyrazolopyridines with potent activity against herpesviruses: effects of C5
      substituents on antiviral activity.
AB  - Synthesis of a series of 5-substituted as well as 5,7-disubstituted 3-[2
      (cyclopentylamino)-4-pyrimidinyl]-2-phenylpyrazolo[1,5-a]pyridin-7-amines with
      potent activity against herpes simplex viruses is described. Synthetic approaches
      allowing for variation of the substitution pattern are outlined and resulting
      changes in antiviral activity are highlighted. Several compounds with in vitro
      antiviral activity similar to or better than acyclovir are described.

PMID- 18086524
TI  - Glycopolydiacetylene nanoparticles as a chromatic biosensor to detect Shiga-like
      toxin producing Escherichia coli O157:H7.
AB  - Shiga toxin-producing Escherichia coli organisms (STEC) were detected by Gal
      alpha1,4-Gal glycopolydiacetylene (GPDA) nanoparticles through the selective
      binding between Shiga toxin and GPDA nanoparticles. The binding produced a
      colorimetric change in the absorption wavelength of the GPDA nanoparticles. This
      method provides a highly selective, rapid, sensitive, and quantitative approach
      for the detection of STEC.

PMID- 18086525
TI  - Synthesis and antibiotic activity of a small molecules library of 1,2,3-triazole
      derivatives.
AB  - A small library of simple 1,4-disubstituted 1,2,3-triazoles was prepared using a
      known one-pot procedure starting from organic halides and terminal alkynes. The
      compounds were then tested for their antibacterial activity against normal and
      resistant species of Staphylococcus aureus.

PMID- 18086526
TI  - beta-N-Biaryl ether sulfonamide hydroxamates as potent gelatinase inhibitors:
      part 1. Design, synthesis, and lead identification.
AB  - A new series of beta-N-biaryl ether sulfonamide hydroxamates as novel gelatinase
      inhibitors is described. These compounds exhibit good potency for MMP-2 and MMP-9
      without inhibiting MMP-1. The structure-activity relationships (SAR) reveal the
      biaryl ether type P1' moiety together with methanesulfonamide is the optimal
      combination that provides inhibitory activity of MMP-9 in the single-digit
      nanomolar range.

PMID- 18086527
TI  - Molecular modeling study and synthesis of novel pyrrolo[2,3-d]pyrimidines and
      pyrrolotriazolopyrimidines of expected antitumor and radioprotective activities.
AB  - Novel pyrrolo[2,3-d]pyrimidine derivatives 4a-e, 10, 14, 15,
      pyrazolopyrrolopyrimidine 13, pyrrolotriazolopyrimidine 5-9, 17 and
      pyrrolopyrimidotriazine 18 are reported herein. The design of these compounds was
      based upon the molecular modeling simulation of the fitting values and
      conformational energy values of the best-fitted conformers to VEGFRTK inhibitor
      hypothesis. This hypothesis was generated from its corresponding lead compounds
      using CATALYST software. The structures of these compounds were confirmed by
      microanalyses, IR, (1)H NMR, and mass spectral data. Compounds 6 and 15 showed
      interesting in vitro antitumor activity compared to doxorubicin as positive
      control. These results are nearly consistent with the molecular modeling studies.
      Docking studies were made on compound 15 to predict its binding mode. Moreover,
      compound 10 exhibited a significant radioprotective activity.

PMID- 18086528
TI  - Thiahomoisocitrate: a highly potent inhibitor of homoisocitrate dehydrogenase
      involved in the alpha-aminoadipate pathway.
AB  - Homoisocitrate dehydrogenase is involved in the alpha-aminoadipate pathway of L
      lysine biosynthesis in higher fungi such as yeast and human pathogenic fungi.
      This enzyme catalyzes the oxidative decarboxylation of (2R,3S)-homoisocitrate
      into 2-ketoadipate using NAD(+) as a coenzyme. A series of aza-, oxa-, and thia
      analogues of homoisocitrate was designed and synthesized as an inhibitor for
      homoisocitrate dehydrogenase. Among them, thia-analogue showed strong competitive
      inhibitory activity as K(i)=97 nM toward homoisocitrate dehydrogenase derived
      from Saccharomyces cerevisiae. Kinetic studies suggested that the formation of
      the enolate intermediate played an important role in inhibition.

PMID- 18086529
TI  - Assurance of the traceability chain for 131I measurement.
AB  - The paper presents some recent results of the Radionuclide Metrology Laboratory
      (RML) from IFIN-HH, concerning the assurance of the international traceability
      for the measurement of (131)I solution aimed to continue the national chain for
      nuclear medicine applications in Romania. The following sequences of the
      traceability are presented: the absolute standardization of solution by the
      4pibeta-gamma coincidence, efficiency extrapolation method and participation in
      the BIPM.RI(II)-K1.I-131 key comparison; and recalibration of the CENTRONIC
      IG12/20A ionization chamber secondary standard. The participation in the
      IAEA/SSDL (SSRL) (131)I comparison is also presented.

PMID- 18086531
TI  - Study of UVA irradiation on hemoglobin in the presence of NADH.
AB  - Reduction of ferric methemoglobin (metHb) to its ferrous form is observed by
      short-time ultraviolet A (UVA) irradiation of metHb together with nicotinamide
      adenine dinucleotide (NADH). And, severely structural destruction of metHb occurs
      when long-time UVA irradiation is exerted. However, neither reduction nor
      destruction can be observed in the absence of NADH under otherwise the same
      experimental conditions. Accordingly, the O2-binding ability of the protein
      increases by short-time UVA irradiation of metHb together with NADH, which
      corresponds with the reduction of metHb, while it decreases by long-time UVA
      irradiation, which corresponds with the structural destruction. Besides, it is
      found that the reduction reaction and the conformational destruction proceed more
      rapidly with higher concentrations of NADH.

PMID- 18086530
TI  - Cholesterol retention in Alzheimer's brain is responsible for high beta- and
      gamma-secretase activities and Abeta production.
AB  - Alzheimer's disease (AD) is characterized by overproduction of A beta derived
      from APP cleavage via beta- and gamma-secretase pathway. Recent evidence has
      linked altered cholesterol metabolism to AD pathogenesis. In this study, we show
      that AD brain had significant cholesterol retention and high beta- and gamma
      secretase activities as compared to age-matched non-demented controls (ND). Over
      one-half of AD patients had an apoE4 allele but none of the ND. beta- and gamma
      secretase activities were significantly stimulated in vitro by 40 and 80 microM
      cholesterol in AD and ND brains, respectively. Both secretase activities in AD
      brain were more sensitive to cholesterol (40 microM) than those of ND (80
      microM). Filipin-stained cholesterol overlapped with BACE and A beta in AD brain
      sections. Cholesterol (10-80 microM) added to N2a cultures significantly
      increased cellular cholesterol, beta- and gamma-secretase activities and A beta
      secretion. Similarly, addition of cholesterol (20-80 microM) to cell lysates
      stimulated both in vitro secretase activities. Ergosterol slightly decreased beta
      secretase activity at 20-80 microM, but strongly inhibited gamma-secretase
      activity at 40 microM. Cholesterol depletion reduced cellular cholesterol, beta
      secretase activity and A beta secretion. Transcription factor profiling shows
      that several key nuclear receptors involving cholesterol metabolism were
      significantly altered in AD brain, including decreased LXR-beta, PPAR and TR, and
      increased RXR. Treatment of N2a cells with LXR, RXR or PPAR agonists strongly
      stimulated cellular cholesterol efflux to HDL and reduced cellular cholesterol
      and beta-/gamma-secretase activities. This study provides direct evidence that
      cholesterol homeostasis is impaired in AD brain and suggests that altered levels
      or activities of nuclear receptors may contribute to cholesterol retention which
      likely enhances beta- and gamma-secretase activities and A beta production in
      human brain.

PMID- 18086533
TI  - The effects of exercise on spatial learning and anxiety-like behavior are
      mediated by an IGF-I-dependent mechanism related to hippocampal neurogenesis.
AB  - Knowledge about the effects of physical exercise on brain is accumulating
      although the mechanisms through which exercise exerts these actions remain
      largely unknown. A possible involvement of adult hippocampal neurogenesis (AHN)
      in the effects of exercise is debated while the physiological and pathological
      significance of AHN is under intense scrutiny. Recently, both neurogenesis
      dependent and independent mechanisms have been shown to mediate the effects of
      physical exercise on spatial learning and anxiety-like behaviors. Taking
      advantage that the stimulating effects of exercise on AHN depend among others, on
      serum insulin-like growth factor I (IGF-I), we now examined whether the
      behavioral effects of running exercise are related to variations in hippocampal
      neurogenesis, by either increasing or decreasing it according to serum IGF-I
      levels. Mutant mice with low levels of serum IGF-I (LID mice) had reduced AHN
      together with impaired spatial learning. These deficits were not improved by
      running. However, administration of exogenous IGF-I ameliorated the cognitive
      deficit and restored AHN in LID mice. We also examined the effect of exercise in
      LID mice in the novelty-suppressed feeding test, a measure of anxiety-like
      behavior in laboratory animals. Normal mice, but not LID mice, showed reduced
      anxiety after exercise in this test. However, after exercise, LID mice did show
      improvement in the forced swim test, a measure of behavioral despair. Thus, many,
      but not all of the beneficial effects of exercise on brain function depend on
      circulating levels of IGF-I and are associated to increased hippocampal
      neurogenesis, including improved cognition and reduced anxiety.

PMID- 18086532
TI  - Interleukin-15 increases Paracoccidioides brasiliensis killing by human
      neutrophils.
AB  - Interleukin-15 is a cytokine produced by a wide range of different cell types,
      including macrophages, in response to lipopolysaccharide or microbial infection.
      This cytokine may play a crucial role in the activation of phagocytic cells
      against pathogens, especially during innate immune response. The effects of IL-15
      on human polymorphonuclear leukocyte fungicidal activity against a highly
      virulent Paracoccidioides brasiliensis strain were investigated. Pretreatment of
      human neutrophils from healthy individuals with IL-15 for 18 hours increased cell
      fungicidal activity in a dose-dependent manner. In addition, the exposure to IL
      15 induced an increase in neutrophil oxidative burst as evaluated by superoxide
      anion and H(2)O(2) release. Catalase inhibited fungicidal activity supporting a
      role for H(2)O(2) in fungus killing. In contrast, IL-8 and TNF-alpha levels were
      not affected by IL-15 suggesting that its effects were not mediated by these
      cytokines. Together, these results show that IL-15 is a potent stimulant of
      antifungal activities in human neutrophils, at least in part by a mechanism
      dependent on oxidative metabolism.

PMID- 18086534
TI  - Rational protein engineering in action: the first crystal structure of a
      phenylalanine tRNA synthetase from Staphylococcus haemolyticus.
AB  - In this article, we describe for the first time the high-resolution crystal
      structure of a phenylalanine tRNA synthetase from the pathogenic bacterium
      Staphylococcus haemolyticus. We demonstrate the subtle yet important structural
      differences between this enzyme and the previously described Thermus thermophilus
      ortholog. We also explain the structure-activity relationship of several recently
      reported inhibitors. The native enzyme crystals were of poor quality--they only
      diffracted X-rays to 3-5A resolution. Therefore, we have executed a rational
      surface mutagenesis strategy that has yielded crystals of this 2300-amino acid
      multidomain protein, diffracting to 2A or better. This methodology is discussed
      and contrasted with the more traditional domain truncation approach.

PMID- 18086535
TI  - Unconscious auditory information can prime visual word processing: a process
      dissociation procedure study.
AB  - Whether information perceived without awareness can affect overt performance, and
      whether such effects can cross sensory modalities, remains a matter of debate.
      Whereas influence of unconscious visual information on auditory perception has
      been documented, the reverse influence has not been reported. In addition,
      previous reports of unconscious cross-modal priming relied on procedures in which
      contamination of conscious processes could not be ruled out. We present the first
      report of unconscious cross-modal priming when the unaware prime is auditory and
      the test stimulus is visual. We used the process-dissociation procedure [Debner,
      J. A., & Jacoby, L. L. (1994). Unconscious perception: Attention, awareness and
      control. Journal of Experimental Psychology: Learning, Memory, and Cognition, 20,
      304-317] which allowed us to assess the separate contributions of conscious and
      unconscious perception of a degraded prime (either seen or heard) to performance
      on a visual fragment-completion task. Unconscious cross-modal priming (auditory
      prime, visual fragment) was significant and of a magnitude similar to that of
      unconscious within-modality priming (visual prime, visual fragment). We conclude
      that cross-modal integration, at least between visual and auditory information,
      is more symmetrical than previously shown, and does not require conscious
      mediation.

PMID- 18086536
TI  - High frequency rTMS modulation of the sensorimotor networks: behavioral changes
      and fMRI correlates.
AB  - Repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex
      (M1) may induce functional modulation of motor performance and sensory
      perception. To address the underlying neurophysiological modulation following 10
      Hz rTMS applied over M1, we examined cortical activation using 3T functional
      magnetic resonance imaging (fMRI), as well as the associated motor and sensory
      behavioral changes. The motor performance measure involved a sequential finger
      motor task that was also used as an activation task during fMRI. For sensory
      assessment, current perception threshold was measured before and after rTMS
      outside the MR scanner, and noxious mechanical stimulation was used as an
      activation task during fMRI. We found that significant activation in the
      bilateral basal ganglia, left superior frontal gyrus, bilateral pre-SMA, right
      medial temporal lobe, right inferior parietal lobe, and right cerebellar
      hemisphere correlated with enhanced motor performance in subjects that received
      real rTMS compared with sham-stimulated controls. Conversely, significant
      deactivation in the right superior and middle frontal gyri, bilateral postcentral
      and bilateral cingulate gyri, left SMA, right insula, right basal ganglia, and
      right cerebellar hemisphere were associated with an increase in the sensory
      threshold. Our findings reveal that rTMS induced rapid changes in the
      sensorimotor networks associated with sensory perception and motor performance
      and demonstrate the complexity of such intervention.

PMID- 18086537
TI  - Constraining the cortical face network by neuroimaging studies of acquired
      prosopagnosia.

PMID- 18086538
TI  - A microscopic technique to study kinetics and concentration-response of drug
      induced caspase-3 activation on a single cell level.
AB  - INTRODUCTION: Induction of apoptosis is perceived as the main intention of drug
      regimens for tumour therapy. Thus, the concentration- and time-dependence of drug
      induced apoptosis should be carefully evaluated for experimental as well as for
      standard anti-tumour agents. A main feature of apoptosis is the activation of
      caspases which is a specific phenomenon of the individual cell. Since caspase-3
      is one of the key enzymes we developed a fluorescence microscopy technique to
      detect caspase-3 activity on the single cell level. The results obtained with
      this technique were compared to a biochemical procedure investigating caspase-3
      activation in a cell population. METHODS: For the single cell assay LoVo
      adenocarcinoma cells were stably transfected with the vector pCaspase3-Sensor.
      The activated caspase-3 cleaves the cytosolic fusion protein and its EYFP part
      translocates into the nucleus. Thus, each individual apoptotic cell displays a
      labelled nucleus and affected cells can be visually quantified by the use of a
      fluorescence microscope. To study kinetics and concentration-response of drug
      induced caspase-3 activation we exposed cells towards trans-beta-nitrostyrene, a
      rapidly acting experimental agent, as well as towards 5-fluorouracil, a standard
      agent with slow pro-apoptotic kinetics. RESULTS: Viability tests confirmed a
      comparable cytotoxic sensitivity of the transfected LoVo(EYFP) and the parental
      non-transfected cells towards trans-beta-nitrostyrene, a rapidly acting
      experimental agent, as well as towards 5-fluorouracil, a standard agent with slow
      kinetics. When comparing both caspase-3 assays at the same time points and
      concentrations of both agents, the new microscopic assay proved to be more
      sensitive, especially at lower concentrations and at earlier time points.
      DISCUSSION: Thus, visual detection of caspase activation in each affected cells
      enabled a more careful evaluation of the concentration- and time-dependence of
      drug-induced apoptosis which should also be useful with other experimental or
      standard agents or with other tumour cells.

PMID- 18086539
TI  - Post-training administration of corticotropin-releasing hormone (CRH) enhances
      retention of a spatial memory through a noradrenergic mechanism in male rats.
AB  - Hormones released in response to stress play important roles in cognition. In the
      present study, the effects of the stress peptide, corticotropin-releasing hormone
      (CRH), on spatial reference memory were assessed following post-training
      administration. Adult Long-Evans male rats were trained for 6 days on a standard
      water maze task of reference memory in which animals must learn and remember the
      fixed location of a hidden, submerged platform. Each day, immediately following
      three training trials, rats received bilateral infusions of CRH into the lateral
      ventricles over a range of doses (0.1, 0.33, 1.0, 3.3 microg) or a vehicle
      solution. Post-training infusions of CRH improved retention as indicated by
      significantly shorter latencies and path lengths to locate the hidden platform on
      the first training (retention) trial of days 2 and 3. Additionally, post-training
      administration of CRH increased spatial bias during probe trials as measured by
      proximity to the platform location. CRH did not enhance performance on retention
      or probe trials when administered 2h after daily training indicating that CRH
      facilitated consolidation specifically. The effects of CRH were attenuated by
      intraventricular co-administration of the beta-adrenergic antagonist, propanolol,
      at bilateral doses that had no effect on retention alone (0.1, 1.0 microg).
      Results indicate that post-training administration of CRH enhanced spatial memory
      as measured in a water maze, and this effect was mediated, at least partly, by a
      noradrenergic mechanism.

PMID- 18086540
TI  - Re: Pressman, M. Response to Rosalind Cartwright's letter to the editor. Sleep
      Medicine Reviews 2007; 11(4): 329-333.

PMID- 18086541
TI  - Do psychosocial factors predict disability and health at a 3-year follow-up for
      patients with non-acute musculoskeletal pain? A validation of the Orebro
      Musculoskeletal Pain Screening Questionnaire.
AB  - PURPOSE: Early identification and intervention with those that run the risk of
      developing long-term disability would offer a great opportunity for reducing
      costs and personal suffering associated with long-term work absenteeism. The
      Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ) has been used and
      validated in several studies for participants with mainly acute pain problems.
      The aim of this study was to validate the OMPSQ for patients with non-acute pain
      problems (e.g. 1-6 months sick leave) and compare to other relevant
      questionnaires. METHOD: One hundred and fifty-eight patients with musculoskeletal
      pain and disability recruited to a multidisciplinary rehabilitation project
      completed a battery of questionnaires at baseline and at 3-year follow-up visits.
      The main analysis involved the relationship between risk levels in the
      questionnaire and sick leave and perceived health after 3 years. RESULTS: The
      OMSPQ predicted future sick leave and health and was found to have six factors.
      The function and pain factors were the best predictors of sick leave after 3
      years, while the distress factor was the best predictor of perceived mental
      health and return to work-expectancy was borderline significant. Perceived
      physical health at 3 years was best predicted by the function and pain factors
      with the fear-avoidance factor being marginally significant. CONCLUSION: The
      results demonstrate that psychosocial factors as measured by OMPSQ are related to
      work disability and perceived health even 3 years after treatment for patients
      with non-acute pain problems. The OMSPQ was a good predictor of outcome.

PMID- 18086542
TI  - PGSTE-WATERGATE: an STE-based PGSE NMR sequence with excellent solvent
      suppression.
AB  - A new stimulated-echo based pulsed gradient spin-echo NMR diffusion sequence
      incorporating WATERGATE solvent suppression, PGSTE-WATERGATE, is presented. The
      sequence provides superb solvent suppression without any phase distortions. The
      sequence is simple to set up and particularly suited to measuring diffusion
      coefficients in aqueous solution such as is commonly required in pharmaceutical
      and combinatorial applications. The utility of the sequence is demonstrated on
      samples containing lysozyme and sucrose. Importantly, the high degree of phase
      distortion suppression allows more complicated selective pi pulses to be used to
      enhance the selectivity of solvent suppression.

PMID- 18086543
TI  - The effectiveness of 1H decoupling in the 13C MAS NMR of paramagnetic solids: an
      experimental case study incorporating copper(II) amino acid complexes.
AB  - The use of continuous-wave (CW) 1H decoupling has generally provided little
      improvement in the 13C MAS NMR spectroscopy of paramagnetic organic solids.
      Recent solid-state 13C NMR studies have demonstrated that at rapid magic-angle
      spinning rates CW decoupling can result in reductions in signal-to-noise and that
      1H decoupling should be omitted when acquiring 13C MAS NMR spectra of
      paramagnetic solids. However, studies of the effectiveness of modern 1H
      decoupling sequences are lacking, and the performance of such sequences over a
      variety of experimental conditions must be investigated before 1H decoupling is
      discounted altogether. We have studied the performance of several commonly used
      advanced decoupling pulse sequences, namely the TPPM, SPINAL-64, XiX, and eDROOPY
      sequences, in 13C MAS NMR experiments performed under four combinations of the
      magnetic field strength (7.05 or 11.75T), rotor frequency (15 or 30kHz), and 1H
      rf-field strength (71, 100, or 140kHz). The effectiveness of these sequences has
      been evaluated by comparing the 13C signal intensity, linewidth at half-height,
      LWHH, and coherence lifetimes, T2('), of the methine carbon of copper(II) bis(dl
      alanine) monohydrate, Cu(ala)(2).H2O, and methylene carbon of copper(II) bis(dl-2
      aminobutyrate), Cu(ambut)(2), obtained with the advanced sequences to those
      obtained without 1H decoupling, with CW decoupling, and for fully deuterium
      labelled samples. The latter have been used as model compounds with perfect 1H
      decoupling and provide a measure of the efficiency of the 1H decoupling sequence.
      Overall, the effectiveness of 1H decoupling depends strongly on the decoupling
      sequence utilized, the experimental conditions and the sample studied. Of the
      decoupling sequences studied, the XiX sequence consistently yielded the best
      results, although any of the advanced decoupling sequences strongly outperformed
      the CW sequence and provided improvements over no 1H decoupling. Experiments
      performed at 7.05T demonstrate that the XiX decoupling sequence is the least
      sensitive to changes in the 1H transmitter frequency and may explain the superior
      performance of this decoupling sequence. Overall, the most important factor in
      the effectiveness of 1H decoupling was the carbon type studied, with the
      methylene carbon of Cu(ambut)(2) being substantially more sensitive to 1H
      decoupling than the methine carbon of Cu(ala)(2).H2O. An analysis of the various
      broadening mechanisms contributing to 13C linewidths has been performed in order
      to rationalize the different sensitivities of the two carbon sites under the four
      experimental conditions.

PMID- 18086544
TI  - GC-MS determined cotinine in an epidemiological study on smoking status at
      delivery.
AB  - The objective of this study was to measure the plasma cotinine levels in pregnant
      women and their newborns using a gas chromatography-mass spectrometry (GC-MS)
      method in an epidemiological-delivered population with a wide range of tobacco
      intakes. Nearly 1000 pregnant women from regional maternity wards (n=1007) were
      selected for the study. Each patient kept a tobacco diary and underwent a blood
      test to assess cotinine levels and at the same time that the newborns' cordonal
      plasma was taken. These values were then cross-checked. Cotinine was estimated
      using a selected-ion monitoring mode with a 1.5 ng/ml quantification limit. The
      cotinine levels in mothers and newborns were highly correlated, whatever the
      mother's smoking status, with a calculated cut-off for cotinine levels in active
      smokers of 21.5 ng/ml. Finally, the cotinine determined through this GC-MS method
      offered a sensitive and accurate measure of tobacco exposition of the pregnant
      women and their babies.

PMID- 18086545
TI  - Identification and characterization of the receptor for the Bacillus sphaericus
      binary toxin in the malaria vector mosquito, Anopheles gambiae.
AB  - The binary toxin (Bin) from Bacillus sphaericus exhibits a highly insecticidal
      activity against Culex and Anopheles mosquitoes. The cytotoxicity of Bin requires
      an interaction with a specific receptor present on the membrane of midgut
      epithelial cells in larvae. A direct correlation exists between binding affinity
      and toxicity. The toxin binds with high affinity to its receptor in its primary
      target, Culex pipiens, and displays a lower affinity to the receptor in Anopheles
      gambiae, which is less sensitive to Bin. Although the Bin receptor has previously
      been identified and named Cpm1 in C. pipiens, its structure in Anopheles remains
      unknown. In this study, we hypothesize that the Anopheles Bin receptor is an
      ortholog of Cpm1. By screening the Anopheles genomic database, we identified a
      candidate gene (Agm3) which is expressed primarily on the surface of midgut cells
      in larvae and which functions as a receptor for Bin. A Cpm1-like gene is also
      present in the Bin-refractory species Aedes aegypti. Overall, our results
      indicate that the three mosquito genes examined share a very similar organization
      and are strongly conserved at the amino acid level, in particular in the NH(2)
      terminus, a region believed to contain the ligand binding site, suggesting that
      relatively few amino acids residues are critical for high affinity binding of the
      toxin.

PMID- 18086546
TI  - An investigation of predictors of renal insufficiency following treatment of
      hyperthyroidism in cats.
AB  - To determine if routine pre-treatment clinical data can be used to predict the
      development of overt renal insufficiency following treatment of feline
      hyperthyroidism, we studied retrospectively all non-azotemic cats undergoing
      treatment for hyperthyroidism at our hospital. Medical records were reviewed for
      signalment, clinical signs, and serum biochemical, hematologic and urinalysis
      parameters before and after treatment for hyperthyroidism. Two groups - cats that
      developed post-treatment renal insufficiency, and those that did not - were
      compared. No significant differences could be detected between the groups with
      respect to the parameters measured. Our study suggests that the results of
      routine pre-treatment clinical data cannot be used to reliably predict renal
      function after treatment for hyperthyroidism, validating the necessity of a
      methimazole trial prior to definitive therapy. The widely held belief that cats
      with pre-treatment urine specific gravity>1.035 are at less risk for development
      of renal azotemia after treatment of hyperthyroidism seems unwarranted.

PMID- 18086547
TI  - Do features of public open spaces vary according to neighbourhood socio-economic
      status?
AB  - This study examined the relations between neighbourhood socio-economic status and
      features of public open spaces (POS) hypothesised to influence children's
      physical activity. Data were from the first follow-up of the Children Living in
      Active Neighbourhoods (CLAN) Study, which involved 540 families of 5-6 and 10-12
      year-old children in Melbourne, Australia. The Socio-Economic Index for Areas
      Index (SEIFA) of Relative Socio-economic Advantage/Disadvantage was used to
      assign a socioeconomic index score to each child's neighbourhood, based on
      postcode. Participant addresses were geocoded using a Geographic Information
      System. The Open Space 2002 spatial data set was used to identify all POS within
      an 800 m radius of each participant's home. The features of each of these POS
      (1497) were audited. Variability of POS features was examined across quintiles of
      neighbourhood SEIFA. Compared with POS in lower socioeconomic neighbourhoods, POS
      in the highest socioeconomic neighbourhoods had more amenities (e.g. picnic
      tables and drink fountains) and were more likely to have trees that provided
      shade, a water feature (e.g. pond, creek), walking and cycling paths, lighting,
      signage regarding dog access and signage restricting other activities. There were
      no differences across neighbourhoods in the number of playgrounds or the number
      of recreation facilities (e.g. number of sports catered for on courts and ovals,
      the presence of other facilities such as athletics tracks, skateboarding facility
      and swimming pool). This study suggests that POS in high socioeconomic
      neighbourhoods possess more features that are likely to promote physical activity
      amongst children.

PMID- 18086548
TI  - Catathrenia: a rare parasomnia which may mimic central sleep apnea on
      polysomnogram.

PMID- 18086550
TI  - Antagonistic and agonistic effects of indigoids on the transformation of an aryl
      hydrocarbon receptor.
AB  - Halogenated and polycyclic aromatic hydrocarbons, exogenous ligands of the aryl
      hydrocarbon receptor (AhR), cause various toxicological effects through the
      transformation of the AhR. In this study, we investigated the antagonistic
      effects of indigoids on the transformation in addition to their agonistic ones.
      In a cell-free system, indigoids induced the transformation dose-dependently, but
      suppressed the transformation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and
      the binding of 3-methylcholanthrene to the AhR. In mouse hepatoma Hepa-1c1c7
      cells, indigoids, especially indirubin, suppressed the transformation and
      expression of CYP1A1 by inhibiting the translocation of AhR into the nucleus.
      When orally administered to mice at 10mg/kg BW/day for three successive days,
      indigoids did not induce AhR transformation and expression of the CYP1A subfamily
      in the liver, while indirubin and indigo upregulated quinone reductase activity.
      These results indicate that indigoids are able to bind to the AhR as ligands and
      exhibit antagonistic effects at lower concentrations in mammalian cells.

PMID- 18086553
TI  - Establishment of a novel high-affinity IgE receptor-positive canine mast cell
      line with wild-type c-kit receptors.
AB  - Much is known regarding participations of mast cells with innate and acquired
      immunity by secreting various cytokines and chemical mediators. However, details
      of mast cell biology still remain unclear. In this study, we successfully
      established a novel growth factor-independent mast cell line (MPT-1) derived from
      canine mast cell tumor. MPT-1 cells manifested factor-independent proliferation
      as floating cells containing a large amount of histamine, as well as chymase-like
      dog mast cell protease 3, in cytosolic granules. Particularly, MPT-1 cells
      expressed high-affinity IgE receptors (FcepsilonRI) and wild-type c-kit
      receptors. Degranulation of MPT-1 cells was induced not only by stimulation with
      calcium ionophore but also by cross-linkage of the surface IgE. Given that MPT-1
      is the first mast cell line with FcepsilonRI which has no c-kit mutations, MPT-1
      cells may provide great contribution for investigation of IgE-mediated activation
      mechanisms of mast cells, leading to development of effective treatment for
      allergic disorders.

PMID- 18086552
TI  - Interactions of tight junctions with membrane channels and transporters.
AB  - Tight junctions are unique organelles in epithelial cells. They are localized to
      the apico-lateral region and essential for the epithelial cell transport
      functions. The paracellular transport process that occurs via tight junctions is
      extensively studied and is intricately regulated by various extracellular and
      intracellular signals. Fine regulation of this transport pathway is crucial for
      normal epithelial cell functions. Among factors that control tight junction
      permeability are ions and their transporters. However, this area of research is
      still in its infancy and much more needs to be learned about how these molecules
      regulate tight junction structure and functions. In this review we have attempted
      to compile literature on ion transporters and channels involved in the regulation
      of tight junctions.

PMID- 18086551
TI  - Kinetics of electron transfer in the complex of cytochrome P450 3A4 with the
      flavin domain of cytochrome P450BM-3 as evidence of functional heterogeneity of
      the heme protein.
AB  - We used a rapid scanning stop-flow technique to study the kinetics of reduction
      of cytochrome P450 3A4 (CYP3A4) by the flavin domain of cytochrome P450-BM3
      (BMR), which was shown to form a stoichiometric complex (K(D)=0.48 microM) with
      CYP3A4. In the absence of substrates only about 50% of CYP3A4 was able to accept
      electrons from BMR. Whereas the high-spin fraction was completely reducible, the
      reducibility of the low-spin fraction did not exceed 42%. Among four substrates
      tested (testosterone, 1-pyrenebutanol, bromocriptine, or alpha-naphthoflavone
      (ANF)) only ANF is capable of increasing the reducibility of the low-spin
      fraction to 75%. Our results demonstrate that the pool of CYP3A4 is
      heterogeneous, and not all P450 is competent for electron transfer in the complex
      with reductase. The increase in the reducibility of the enzyme in the presence of
      ANF may represent an important element of the mechanism of action of this
      activator.

PMID- 18086554
TI  - Identification and characterization of the novel centrosomal protein centlein.
AB  - Centrosomes function as the major microtubule (MT)-organizing center. They are
      composed of a pair of centrioles which are surrounded by the pericentriolar
      material. Here, we describe the molecular characterization of a novel protein,
      named centlein (centrosomal protein). Centlein was a protein of 721 amino acids
      with a calculated molecular weight of 82,717 and possessed coiled-coil domains.
      Western blot analysis indicated that centlein was ubiquitously expressed.
      Endogenous centlein as well as enhanced green fluorescent protein-fused centlein
      was localized at centrosomes in interphase and mitosis. When centrosomes were
      isolated from cells treated with nocodazole, an MT-disrupting agent, centlein and
      the centrosomal protein, gamma-tubulin, were enriched in the same fractions.
      These data indicate that centlein is a widespread centrosomal protein and that
      its association with centrosomes is independent of MTs. Centlein appeared to be
      enriched in the mother centriole in G1 phase, suggesting possible involvement of
      centlein in mother-centriole-related functions, such as duplication of centrioles
      and generation of primary cilia.

PMID- 18086555
TI  - Bacteriovorax stolpii proliferation and predation without sphingophosphonolipids.
AB  - Bacteriovorax stolpii strain UKi2, a facultative predator-parasite of larger Gram
      negative bacteria, synthesizes distinct sphingophosphonolipids. These lipids are
      characterized by a direct P-C bond, the novel head group 1-hydroxy-2
      aminoethylphosphonate, iso-branched long chain bases and fatty acids, and fatty
      acids dominated by those with alpha-hydroxy groups. Myriocin, an inhibitor of
      serine:fatty acyl CoA transferase, reversibly blocked sphingophosphonolipid
      synthesis in B. stolpii UKi2. However, the inhibitor did not block cell
      proliferation indicating that these lipids are not vital for B. stolpii UKi2
      viability and growth. When mixed with Escherichia coli prey cells, control
      predator-parasite bacteria were effective in forming large E. coli bdelloplasts
      and cleared the suspension of the prey cells. Although myriocin-treated cells
      could attack prey cells and form bdelloplasts, their locomotory behavior was
      altered and fewer and smaller bdelloplasts were produced. These observations open
      up the possibility for a role of sphingophosphonolipids in B. stolpii UKi2
      complex behavior.

PMID- 18086556
TI  - Yeast adaptation to mancozeb involves the up-regulation of FLR1 under the
      coordinate control of Yap1, Rpn4, Pdr3, and Yrr1.
AB  - FLR1 gene, encoding a multidrug resistance (MDR) transporter of the major
      facilitator superfamily (MFS) was found to confer resistance to the fungicide
      mancozeb in Saccharomyces cerevisiae. This agrochemical has been linked to the
      development of Parkinson disease and cancer. Yeast response to mancozeb was
      proved to involve the strong activation of FLR1 transcription (20-fold) during
      the fungicide-induced growth latency. This activation of FLR1 transcription is
      fully dependent on Yap1p and is reduced (by 50%) in the absence of Rpn4p, Yrr1p
      or Pdr3p. A model for the coordinate action over FLR1 transcription activation,
      in response to mancozeb, of these transcription factors that mediate oxidative
      stress response (Yap1p), proteasome gene expression (Rpn4p), and pleiotropic drug
      resistance (Pdr3p and Yrr1p), is proposed.

PMID- 18086557
TI  - Protease-activated receptor (PAR)-induced interleukin-8 production in airway
      epithelial cells requires activation of MAP kinases p44/42 and JNK.
AB  - The mechanism underlying protease-activated receptor (PAR)-activation and
      subsequent interleukin (IL)-8 production in airway epithelial cells is not yet
      understood. In this study we investigated the role of mitogen-activated protein
      kinases (MAPKs) in A549 airway epithelial cells. We studied the consequence of
      activation of PARs with simultaneous exposure to LPS. Thrombin, PAR-2-activating
      peptide and LPS, were tested alone and in combination. They induced significant
      synthesis of IL-8. However, only activation of PAR triggered phosphorylation of
      ERK1/2 and JNK. The application of the inhibitors of these two MAPKs resulted in
      reduction of IL-8 production. Thus, activation of PARs but not stimulation with
      LPS leads to ERK1/2 and JNK-mediated production of IL-8.

PMID- 18086558
TI  - Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity.
AB  - NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic
      gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in
      hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using
      adenoviral vectors, and demonstrate that these mice exhibit a modulation of the
      plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis
      of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits
      SREBP1c expression. This results in decreased SREBP1c activity as is illustrated
      by reduced expression of its target genes stearoyl-coA desaturase-1,
      mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the
      LDL receptor, and provides a mechanism for the physiological changes observed in
      response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by
      Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on
      SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates
      hepatic lipid metabolism through suppression of SREBP1c activity.

PMID- 18086559
TI  - Leucine-rich amelogenin peptide induces osteogenesis in mouse embryonic stem
      cells.
AB  - Leucine-rich amelogenin peptide (LRAP), an alternatively spliced amelogenin
      protein, possesses a signaling property shown to induce osteogenic
      differentiation. In the current study, we detected LRAP expression during
      osteogenesis of wild-type (WT) embryonic stem (ES) cells and observed the absence
      of LRAP expression in amelogenin-null (KO) ES cells. We explored the signaling
      effect of LRAP on wild-type ES cells, and the ability of LRAP to rescue the
      impaired osteogenesis phenotype observed in KO ES cells. Our data indicate that
      LRAP treatment of WT and KO ES cells induces a significant increase in mineral
      matrix formation, and significant increases in bone sialoprotein and osterix gene
      expression. In addition, the amelogenin KO phenotype is partially rescued by the
      addition of exogenous LRAP. These data suggest a unique function of LRAP during
      ES cell differentiation along osteogenic lineage.

PMID- 18086560
TI  - Poly(rC)-binding protein 2 interacts with the oligo(rC) tract of coxsackievirus
      B3.
AB  - The human poly(rC)-binding protein (PCBP) 2 is known to interact with enteroviral
      RNA. Here, the interaction of PCBP2 with RNA target sequences at the 5' end of
      the coxsackievirus B3 genome was investigated. Using the electrophoretic mobility
      shift assay and the yeast three-hybrid system, a short oligo(rC) tract connecting
      cloverleaf and IRES is demonstrated to contribute to PCBP2 binding. This
      oligo(rC) tract is conserved among entero- and rhinoviruses. In absence of the
      viral 3C proteinase, an extended cloverleaf RNA (nt 1-105) containing the
      oligo(rC) tract interacts with PCBP2 whereas the cloverleaf (nt 1-87) lacking the
      oligo(rC) tract does not. In the presence of 3C proteinase, cloverleaf RNA (1-87)
      interacts with PCBP2.

PMID- 18086561
TI  - Quantitative differential expression analysis reveals miR-7 as major islet
      microRNA.
AB  - MicroRNAs (miRNAs) are non-coding gene products that regulate gene expression
      through specific binding to target mRNAs. Cell-specific patterns of miRNAs are
      associated with the acquisition and maintenance of a given phenotype, such as
      endocrine pancreas (islets). We hypothesized that a subset of miRNAs could be
      differentially expressed in the islets. Using miRNA microarray technology and
      quantitative RT-PCR we identified a subset of miRNAs that are the most
      differentially expressed islet miRNAs (ratio islet/acinar>150-fold), miR-7 being
      the most abundant. A similarly high ratio for miR-7 was observed in human islets.
      The ratio islet/acinar for miR-375, a previously described islet miRNA, was <10
      and is 2.5x more abundant in the islets than miR-7. Therefore, we conclude that
      miR-7 is the most abundant endocrine miRNA in islets while miR-375 is the most
      abundant intra-islet miRNA. Our results may offer new insights into regulatory
      pathways of islet gene expression.

PMID- 18086562
TI  - A heparin binding motif on the pro-domain of human procathepsin L mediates
      zymogen destabilization and activation.
AB  - The molecular mechanism by which heparin modulates the processing of procathepsin
      L in the extracellular environment is proposed. We show that heparin reduces the
      stability of the pro form of cathepsin L at pH 5 by binding to a putative heparin
      binding motif (BBXB) in the pro-domain. Mutations to this motif on procathepsin L
      reduce heparin binding affinity and heparin-induced destabilization; in contrast,
      heparin only slightly destabilizes the mature cathepsin L domain. Gel analysis
      further shows that heparin makes procathepsin L a much better substrate for
      cathepsin L. Thus, heparin enhances the rate of zymogen activation by
      destabilization upon binding to the BBXB motif. Determining the mechanism by
      which procathepsin L is activated in the extracellular matrix is important to the
      understanding of the role that cathepsin L plays in tumour invasion.

PMID- 18086563
TI  - Expression of p107 and p130 during human adipose-derived stem cell adipogenesis.
AB  - Within the first 24h of hormonally stimulated adipocyte differentiation, murine
      3T3-L1 preadipocytes undergo a mitotic expansion phase prior to terminal
      differentiation. During this time, the cell cycle regulatory proteins, p130 and
      p107 undergo dramatic differential expression and the transient increase in
      expression of p107 appears to be required for terminal differentiation. Recently,
      human adipose-derived human stem cells (hASC) of mesenchymal origin have been
      used as a model of human adipocyte differentiation and we sought to determine if
      differentiating hASC undergo clonal expansion and if the regulated expression of
      p130/p107 was similar to that observed during 3T3-L1 adipogenesis. Results
      indicate that differentiating hASC, unlike 3T3-L1 cells do not undergo clonal
      expansion and p130 expression gradually diminishes across differentiation.
      However, p107 expression is transiently increased during hASC differentiation in
      a manner analogous to 3T3-L1 cells suggesting a similar role for p107 in terminal
      differentiation in human adipocytes.

PMID- 18086564
TI  - Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1
      PDGFRalpha.
AB  - The constitutively activated tyrosine kinase Fip1-like 1 (FIP1L1)-platelet
      derived growth factor receptor alpha (PDGFRalpha) causes eosinophilic leukemia
      EoL-1 cells to proliferate. Recently, we demonstrated that histone deacetylase
      inhibitors suppressed this proliferation and induced the differentiation of EoL-1
      cells into eosinophils in parallel with a decrease in the level of FIP1L1
      PDGFRalpha. In this study, we analyzed the mechanism by which FIP1L1-PDGFRalpha
      induces the proliferation and whether the suppression of cell proliferation
      triggers the differentiation into eosinophils. The FIP1L1-PDGFRalpha inhibitor
      imatinib inhibited the proliferation of EoL-1 cells and decreased the level of
      the oncoprotein c-Myc as well as the phosphorylation of extracellular signal
      regulated kinase and c-Jun N-terminal kinase (JNK). The proliferation of EoL-1
      cells and expression of c-Myc were also inhibited by the MEK inhibitor U0126 and
      JNK inhibitor SP600125. The expression of the eosinophilic differentiation marker
      CCR3 was not induced by imatinib. These findings suggest that FIP1L1-PDGFRalpha
      induces the proliferation of EoL-1 cells through the induction of c-Myc
      expression via ERK and JNK signaling pathways, but is not involved in the
      inhibition of differentiation toward mature eosinophils.

PMID- 18086565
TI  - Proteomic identification of ZO-1/2 as a novel scaffold for Src/Csk regulatory
      circuit.
AB  - To elucidate the regulatory mechanism of cell transformation induced by c-Src
      tyrosine kinase, we performed a proteomic analysis of tyrosine phosphorylated
      proteins that interact with c-Src and/or its negative regulator Csk. The c-Src
      interacting proteins were affinity-purified from Src transformed cells using the
      Src SH2 domain as a ligand. LC-MS/MS analysis of the purified proteins identified
      general Src substrates, such as focal adhesion kinase and paxillin, and ZO-1/2 as
      a transformation-dependent Src target. The Csk binding proteins were analyzed by
      a tandem affinity purification method. In addition to the previously identified
      Csk binding proteins, including Cbp/PAG, paxillin, and caveolin-1, we found that
      ZO-1/2 could also serve as a major Csk binding protein. ZO-2 was phosphorylated
      concurrently with Src transformation and specifically bound to Csk in a Csk SH2
      dependent manner. These results suggest novel roles for ZO proteins as Src/Csk
      scaffolds potentially involved in the regulation of Src transformation.

PMID- 18086566
TI  - C314T polymorphism in histamine N-methyltransferase gene and susceptibility to
      duodenal ulcer in Chinese population.
AB  - BACKGROUND: Histamine is a regulator of gastric acid secretion, which is involved
      in the development of duodenal ulcer (DU). Histamine is metabolized by both
      histamine N-methyltransferase (HNMT) and diamine oxidase, and its local action is
      terminated primarily by methylation which is catalyzed by HNMT. METHODS:
      Polymerase chain reaction-restriction fragment length polymorphism assay was used
      to identify the polymorphism of the point mutation C314T of HNMT gene of 498
      Chinese patients with DU and 151 healthy individuals. RESULTS: In normal
      controls, the allele frequency of HNMT T314 was 3.3%, which was significantly
      lower than American Caucasians. The HNMT T314 allele was detected in 3.5% of the
      DU patients. In cases and controls, the frequency of C/C genotypes were 93.0% and
      93.4%, respectively. The HNMT T/T genotype was not found in this population. No
      significant differences were seen in both genotype frequencies and allele
      frequencies between DU groups and controls. After stratified by H. pylori
      infection, they also could not reach significant differences in our current
      study. CONCLUSION: The HNMT T314 allele frequency is lower in Chinese population
      than in American Caucasians. No association can be found in the involvement of
      HNMT C314T polymorphism in the susceptibility to duodenal ulcer.

PMID- 18086567
TI  - Glucose-6-phosphate dehydrogenase Buenos Aires: a novel de novo missense mutation
      associated with severe enzyme deficiency.
AB  - OBJECTIVE: : Glucose 6-phosphate dehydrogenase (G6PD) catalyzes the first
      committed steps in the pentose phosphate pathway: the generation of NADPH by this
      enzyme is essential for protection against oxidative stress. The human enzyme is
      in a dimer<-->tetramer equilibrium and its stability depends on NADP(+)
      concentration. Herein, we report a case of a symptomatic baby affected by severe
      deficiency of G6PD activity due to a novel de novo genetic mutation (g1465C>T) in
      the thirteenth exon of its gene. METHODS: : Clinical, biochemical and genetic
      evaluations of the affected baby and his mother were performed. RESULTS: : We
      found the g1465C>T novel mutation, in the thirteenth exon of G6PD gene (named
      "G6PD Buenos Aires variant"). This g1465C>T mutation produce a P489S substitution
      at protein level. The P489S mutation was absent in his mother, suggesting that
      G6PD Buenos Aires resulted from a de novo mutation. CONCLUSIONS: : The absence of
      mosaicism in the baby's DNA (from saliva and blood samples) suggests that a de
      novo mutation event may occur in the very early stages in embryogenesis or in the
      mother's germ cell lines.

PMID- 18086568
TI  - Gender-related effect of apo E polymorphism on lipoprotein particle sizes in the
      middle-aged subjects.
AB  - OBJECTIVES: We determined the frequencies of apolipoprotein E (apo E) alleles and
      examined the effect of apo E polymorphism on lipoprotein particle sizes in
      Serbian healthy, middle-aged individuals. DESIGN AND METHODS: We performed apo E
      phenotype by immunobloting method in 183 men and 143 women (mean years: 56.3+/
      10.60 and 54.9+/-10.31, respectively). Plasma lipid and apolipoprotein levels
      were measured by routine laboratory methods. LDL and HDL particle sizes were
      determined by nondenaturing polyacrylamide gradient (3-31%) gel electrophoresis.
      RESULTS: The apo E allele frequencies were epsilon2--4.9%, epsilon3--86.5%, and
      epsilon4--8.6%. Men with epsilon4 allele had lower HDL-C and Apo AI
      concentrations than epsilon3 men. The epsilon2 allele men had the smallest LDL
      particles, highest percent of subjects with LDL phenotype B and highest TG/HDL-C
      ratio. Women with epsilon2 allele had lowest concentration of apo B. The epsilon4
      allele women had smallest HDL particles and highest percent of the subjects with
      small-sized HDL phenotype. CONCLUSIONS: This study showed gender-related effect
      of apo E polymorphism on lipoprotein particle size. In men, possession of the
      epsilon2 allele is associated with small LDL particles, whereas in women,
      epsilon4 allele is associated with small HDL particles. Differences in gender
      related influence of apo E polymorphism on LDL and HDL particle sizes could be
      clinically useful in strategy for reduction of coronary disease risk in middle
      aged men and women.

PMID- 18086569
TI  - Hepoxilin A3 (HXA3) synthase deficiency is causative of a novel ichthyosis form.
AB  - Non-bullous congenital ichthyosis erythroderma (NCIE) and lamellar ichthyosis
      (LI) are characterized by mutations in 12R-lipoxygenase (12R-LOX) and/or
      epidermal lipoxygenase 3 (eLOX3) enzymes. The eLOX3 lacks oxygenase activity, but
      is capable of forming hepoxilin-type products from arachidonic acid-derived
      hydroperoxide from 12R-LOX, termed 12R-hydroperoxyeicosa-5,8,10,14-tetraenoic
      acid (12R-HpETE). Mutations in either of two enzymes lead to NCIE or LI.
      Moreover, 12R-LOX-deficient mice exhibit severe phenotypic water barrier
      dysfunctions. Here, we demonstrate that 12R-HpETE can also be transformed to 8R
      HXA(3) by hepoxilin A(3) (HXA(3)) synthase (12-lipoxygenase), which exhibits
      oxygenase activity. We also presented a novel form of ichthyosis in a patient,
      termed hepoxilin A(3) synthase-linked ichthyosis (HXALI), whose scales expressed
      high levels of 12R-LOX, but were deficient of HXA(3) synthase.

PMID- 18086570
TI  - Melanoma cell sensitivity to Docetaxel-induced apoptosis is determined by class
      III beta-tubulin levels.
AB  - We have previously shown that Docetaxel-induced variable degrees of apoptosis in
      melanoma. In this report, we studied the beta-tubulin repertoire of melanoma cell
      lines and show that class III beta-tubulin expression correlated with Docetaxel
      resistance. Sensitive cells showed low levels of class III beta-tubulin with
      little microtubular incorporation, whereas class III beta-tubulin expression was
      higher in resistant cells and was incorporated into the cytoskeleton. As proof of
      concept, abrogation of class III by siRNA reverted Docetaxel-resistant cells to a
      sensitive phenotype, restoring the microtubular polymerisation response and
      promoting high levels of apoptosis through Bax activation. These results suggest
      that phenotypic expression of beta-tubulin class III in melanoma may help
      identify patients with melanoma that can respond to taxanes.

PMID- 18086571
TI  - Rac1 GTPase is activated by hepatitis B virus replication--involvement of HBX.
AB  - Hepatitis B virus (HBV) is a causative agent for liver diseases including
      hepatocellular carcinoma. Understanding its interactions with cellular proteins
      is critical in the elucidation of the mechanisms of disease progression. Using a
      cell-based HBV replication system, we showed that HBV replication in HepG2 cells
      resulted in a cellular morphological changes displaying membrane rufflings and
      lamellipodia like structures reminiscent of cells expressing constitutively
      activated Rac1. We also showed that activated Rac1 resulted in increased viral
      replication. HBV replication specifically activated wild type Rac1, but not
      Cdc42. The Rac1 activation by HBV replication also resulted in the
      phosphorylation of ERK1/2 and AKT, the downstream targets of Rac1 signaling
      cascade. The smallest HBV viral protein, HBX, was able to activate the endogenous
      Rac1 and induce membrane ruffling when transfected into cells. Significantly, HBX
      was found to directly interact with a Rac1 nucleotide exchange factor (betaPIX)
      through a SH3 binding motif. Taken together, we have shown the interaction of HBV
      with the Rho GTPase, affecting cell morphology through the Rac1 activation
      pathway. HBV may possibly make use of an activated Rac1 signaling pathway for
      increased replication and resultant metastatic effects.

PMID- 18086572
TI  - Protein contacts, inter-residue interactions and side-chain modelling.
AB  - Three-dimensional structures of proteins are the support of their biological
      functions. Their folds are stabilized by contacts between residues. Inner protein
      contacts are generally described through direct atomic contacts, i.e.
      interactions between side-chain atoms, while contact prediction methods mainly
      used inter-Calpha distances. In this paper, we have analyzed the protein contacts
      on a recent high quality non-redundant databank using different criteria. First,
      we have studied the average number of contacts depending on the distance
      threshold to define a contact. Preferential contacts between types of amino acids
      have been highlighted. Detailed analyses have been done concerning the proximity
      of contacts in the sequence, the size of the proteins and fold classes. The
      strongest differences have been extracted, highlighting important residues. Then,
      we studied the influence of five different side-chain conformation prediction
      methods (SCWRL, IRECS, SCAP, SCATD and SCCOMP) on the distribution of contacts.
      The prediction rates of these different methods are quite similar. However, using
      a distance criterion between side chains, the results are quite different, e.g.
      SCAP predicts 50% more contacts than observed, unlike other methods that predict
      fewer contacts than observed. Contacts deduced are quite distinct from one method
      to another with at most 75% contacts in common. Moreover, distributions of amino
      acid preferential contacts present unexpected behaviours distinct from previously
      observed in the X-ray structures, especially at the surface of proteins. For
      instance, the interactions involving Tryptophan greatly decrease.

PMID- 18086573
TI  - PPIDD: an extraction and visualisation method of biological protein-protein
      interfaces.
AB  - Today, the information for generating reliable protein-protein complex datasets
      is not directly accessible from PDB structures. Moreover, in X-ray protein
      structures, different types of contacts can be observed between proteins:
      contacts in homodimers or inside heterocomplexes considered to be specific, and
      contacts induced by crystallogenesis processes, considered to be non-specific.
      However, none of the databases giving access to protein-protein complexes allows
      the crystallographic interfaces to be distinguished from the biological
      interfaces. For this reason we developed PPIDD (Protein-Protein Interface
      Description Database), an innovative tool, which allows the extraction and
      visualisation of biological protein-protein interfaces from an annotated subset
      of crystallographic structures of proteins. This tool is focused on the
      description of protein-protein interfaces corresponding to well-identified
      classes of protein assemblies. It permits the representation of any of these
      protein-protein assemblies (duplex) and their interfaces as well as the export of
      the corresponding molecular structures under a flexible format, which is an
      extension of the PDBML. Moreover, PPIDD facilitates the construction of subsets
      of interfaces presenting user-specified common characteristics, to enhance the
      understanding of the determinants of specific protein-protein interactions.

PMID- 18086574
TI  - Analysis of the promoter region of human placenta-specific DSCR4 gene.
AB  - The gene DSCR4 locates in the band q22.2 of human chromosome 21 and encodes a
      protein of 118 amino acids. Expression of DSCR4 is restricted to human placenta
      and placental choriocarcinoma cell lines BeWo and JEG3. The 5'-RACE method using
      RNA from human placenta indicated the major transcription start site at 93 nt
      upstream (nt -93) of the initiation codon. Transfection assay using a series of
      deletion constructs of the 5'-flanking region fused to the luciferase reporter
      gene identified three positive regions nt -2200 to -2088, nt -2064 to -1924, nt 
      810 to -632 and two negative regions nt -1923 to -1740, nt -631 to -425. The
      computer analysis predicted the presence of several cis-elements in these regions
      and the promoter assay using various mutants of consensus sequence identified two
      distinct cis-elements for OLF-1 and E47. The electrophoretic mobility shift assay
      (EMSA) using the extracts of DSCR4-expressing cells confirmed the binding of
      certain protein factors to these cis-elements. In fact, OLF-1-like transcription
      factor, EBF-3 and EBF-4 were detected in the DSCR4-expressing cell lines and
      human placenta. Based on these data, we postulated that transcription of DSCR4
      gene is regulated positively by binding of OLF-1-like transcription factor and
      negatively by binding of E47-like transcription factor.

PMID- 18086575
TI  - Isolation and comparative expression analysis of six MBD genes in wheat.
AB  - The 5-methylcytosines (m5C) play critical roles in epigenetic control, often
      being recognized by proteins containing an MBD. In this study, we isolated six
      wheat cDNAs with open reading frame encoding putative methyl-binding domain
      proteins, which were designated as TaMBD1-TaMBD6, respectively. BLASTX searches
      and phylogenetic analysis suggested that the six TaMBD genes belonged to four (I,
      II, III and VIII) of the eight subclasses of MBD family. Genomic analysis showed
      that a 1386 bp intron was included in TaMBD1 and a 12-bp intron was found in
      TaMBD4. The expression profiles of the six TaMBDs were studied via Q-RT-PCR and
      the results indicated that the TaMBDs were differentially expressed in detected
      wheat tissues. It was interesting to note that 3 TaMBDs were highly expressed in
      dry seeds and endosperms. Moreover, the differential expression patterns of
      TaMBDs were observed in leaves and roots under water-stress. We concluded that
      multiple wheat MBD genes were present and they might play important roles in
      wheat growth and development, as well as in the water-stress response.

PMID- 18086576
TI  - RNA editing in regulating gene expression in the brain.
AB  - Adenosine to inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA
      (ADARs), represents an evolutionary conserved post-transcriptional mechanism
      which harnesses RNA structures to produce proteins that are not literally encoded
      in the genome. The species-specific alteration of functionally important residues
      in a multitude of neuronal ion channels and pre-synaptic proteins through RNA
      editing has been shown to have profound importance for normal nervous system
      function in a wide range of invertebrate and vertebrate model organisms. ADARs
      have also been shown to regulate neuronal gene expression through a remarkable
      variety of disparate processes, including modulation of the RNAi pathway, the
      creation of alternative splice sites, and the abolition of stop codons. In
      addition, ADARs have recently been revealed to have a novel role in the primate
      lineage: the widespread editing of Alu elements, which comprise approximately 10%
      of the human genome. Thus, as well as enabling the cell-specific regulation of
      RNAi and selfish genetic elements, the unshackling of the proteome from the
      constraints of the genome through RNA editing may have been fundamental to the
      evolution of complex behavior.

PMID- 18086577
TI  - Pax3 regulates Wnt1 expression via a conserved binding site in the 5' proximal
      promoter.
AB  - The development of the neural crest is orchestrated by a complex interplay
      between intercellular signalling molecules and transcription factors. Here, we
      demonstrate a direct interaction between two such factors, the paired-type
      transcription factor Pax3 and the secretory glycoprotein Wnt1. We found that the
      Wnt1 promoter can be regulated by Pax3 in a dose-dependent manner. Sequence
      analysis predicted a conserved binding site for Pax3 within the Wnt1 promoter
      region. Deletion or mutation of this sequence abolished the promoter response to
      Pax3. Using chromatin immunoprecipitation (ChIP) assays, we demonstrated that
      Pax3 interacts with the Wnt1 promoter in vivo. These data indicate that Pax3
      directly regulates the expression of Wnt1 in the developing embryo.

PMID- 18086579
TI  - Bite and kick injuries in horses: prevalence, risk factors and prevention.
AB  - REASON FOR PERFORMING STUDY: Studies on the prevalence and predisposing factors
      of bite and kick injuries in horses have not been reported in a population-based
      data sample. OBJECTIVES: To investigate the prevalence of bite and kick injuries
      in horses and associated risk factors in a representative sample of horses in
      Switzerland. METHODS: A questionnaire on the incidence of disease and injury,
      which included the frequency of bite and kick injuries and their association with
      breed, housing, use and feeding regime, was sent to 2559 horse owners randomly
      selected throughout Switzerland. RESULTS: The data of 2912 horses with 897
      disorders diagnosed by a veterinarian were analysed. There were 231 injuries, 50
      (21.6%) caused by a bite or kick from another horse; this number corresponded to
      5.6% of all diseases and injuries and concerned only 1.7% of all the horses
      evaluated. Warmblood, Thoroughbred and Arabian horses had a 4.3 times higher risk
      of bite or kick injuries than horses of other breeds. Eighteen per cent of
      injuries were associated with a change in housing management and occurred
      regardless of whether horses were kept in groups permanently or sporadically.
      CONCLUSIONS AND POTENTIAL RELEVANCE: A stable group hierarchy and a housing
      system that provides adequate space and is adapted to horse-specific behaviour
      are important factors in prevention and kick and bite injuries.

PMID- 18086582
TI  - Crossroads between actinic keratosis and squamous cell carcinoma, and novel
      pharmacological issues.
AB  - Actinic keratoses (AKs) and their derived squamous cell carcinomas are
      distinctive lesions forming a continuum in a multi-step carcinogenesis process.
      They are typically found on chronically sun exposed skin. AKs merit to be
      recognized as such and to be distinguished from squamous cell carcinomas both
      conceptually and for therapeutic implications. The histological differences
      between these lesions are well defined and should not be blurred. A brief review
      is presented about the biological features responsible for AKs and the
      clinicopathologically distinctive aspects of these lesions. In addition, recent
      findings are presented about pharmacotherapy using anti-epidermal growth factor
      receptors, imidazoquinolines, diclofenac-hyaluronan, and methyl aminolevulinate
      photodynamic therapy.

PMID- 18086584
TI  - Association of segmental neurofibromatosis 1 and oculo-auriculo-vertebral
      spectrum in a 24-year-old female.
AB  - Segmental neurofibromatosis 1 (SNF1) is a rare genodermatosis caused by somatic
      mutations in the NF1 gene. It consists of localized characteristic pigmentary
      lesions (i.e. cafe-au-lait spots and freckling) and/or neurofibromas intermingled
      with areas of unaffected skin, often configuring specific mosaic patterns. Oculo
      auriculo-vertebral spectrum (OAVS) is a developmental field defect primarily
      affecting the 1st and 2nd branchial arch derivatives. This condition recognizes a
      wide range of environmental and genetic causes, including postzygotic mutations.
      We report on a 24-year-old female presenting with a constellation of features
      fitting both with SNF1 and OAVS. Neurofibromatosis 1 pigmentary lesions are
      confined to the left arm and adjacent trunk skin surface with sharp midline
      demarcation. OAVS characteristic craniofacial anomalies, including neurosensorial
      hearing loss, hemimandibular and tongue underdevelopment, are homolateral to the
      SNF1 features. Additional findings, such as prearicular tags and multiple costo
      vertebral segmentation defects, mainly involving the cervical and upper thoracic
      metameres, support the diagnosis of OAVS. To our knowledge, this is the first
      published patient who presents with an association of SNF1 and OAVS. The spatial
      relationship between craniofacial and skin pigmentary anomalies has prompted us
      to speculate about the possible underlying pathogenetic mechanism (s).

PMID- 18086585
TI  - Prevalence of piercing in a German population.
AB  - The aim of the present study was to determine the prevalence of piercing in a
      given German population. Questionnaires were given to 5,000 patients of a private
      dental practice, two private dermatology practices and the outpatient Clinic of
      the Department of Dermatology at the University of Regensburg. A total of 4,505
      patients were evaluated. We found 389 patients with piercings other than that of
      earlobes (8.6%). More piercings were found in females (12.9%) than in males
      (4.1%). The study shows a high prevalence of piercings in a given population. For
      that reason, dermatologists ought to be aware of the different types of piercings
      available as well as their short- and long-term complications.

PMID- 18086586
TI  - Safety of pegylated interferon-alpha-2a in adjuvant therapy of intermediate and
      high-risk melanomas.
AB  - Pegylated (PEG)-IFN-alpha-2a is a modified form of recombinant human IFN-alpha-2a
      with sustained absorption and prolonged half-life. Our aim was to evaluate its
      safety profile in adjuvant treatment of high-risk melanoma patients in a single
      centre setting and to compare this safety profile with data obtained from the
      literature for a) low dose IFN-alpha and b) high dose IFN. Eighteen consecutive
      melanoma patients (AJCC 2002 stages IIa-IIIc) were retrospectively analyzed for
      toxicities associated with adjuvant PEG-IFN-alpha-2a (180 microg/week s.c.). The
      most frequently reported adverse events were constitutional side effects (78%),
      myelosuppression (83%) and hepatotoxicity (78%). The proportion of patients
      receiving PEG-IFN-alpha-2a and suffering from myelosuppression and liver toxicity
      was significantly higher than for patients reported in the literature undergoing
      low-dose IFN-alpha treatment (P = 0.008, P = 0.001 respectively), while fatigue
      and depression were seen less frequently with PEG-IFN-alpha-2a. By contrast,
      compared to patients treated with high-dose IFN-alpha, PEG-IFN-alpha-2a treated
      patients less frequently experienced fatigue (P < 0.001), neutropenia (P < 0.068)
      and neuropsychiatric (statistically not significant) adverse events. In
      conclusion, subcutaneously delivered PEG-IFN-alpha-2a is well tolerated in a once
      weekly dose of 180 mug by most patients with high risk malignant melanoma. The
      frequency of side effects is increased compared to low dose, but reduced compared
      to high dose standard IFN-alpha. Due to its pharmacokinetic properties, pegylated
      IFN-alpha has, as in the treatment of hepatitis C, potential for increased
      efficacy in adjuvant therapy of melanoma.

PMID- 18086587
TI  - A new C-xylopyranoside derivative induces skin expression of glycosaminoglycans
      and heparan sulphate proteoglycans.
AB  - Severe structural changes, including deterioration of the mechanical properties
      of the dermis, occur during skin aging. It is well known that the degradation of
      the extracellular matrix contributes to the physical changes in aged skin.
      Whereas many studies have been devoted to age-related alterations of collagen
      fibrils, far less attention has been paid to another major family of
      extracellular matrix components, the glycosaminoglycans (GAGs) and proteoglycans
      (PGs). Heparan sulphate-proteoglycans, (HS-PGs), a subclass of the PG family that
      decreases during aging, regulate proliferation and proteolysis as well as matrix
      adhesion and assembly, and thus, may have important functions in skin. These PGs
      may represent important targets for dermo-cosmetology in fighting skin aging. The
      purpose of this study was to demonstrate the potential of a new C-xylopyranoside
      derivative (C-beta-D-xylopyranoside-2-hydroxy-propane simplified as C-Xyloside)
      to improve HS-PGs expression in human skin. In an organotypical model of
      corticosteroid atrophic human skin, characterized by a decrease of PGs
      expression, treatment with C-Xyloside improved expression of HS-PGs.

PMID- 18086583
TI  - Antimicrobial peptides in human skin disease.
AB  - The skin continuously encounters microbial pathogens. To defend against this,
      cells of the epidermis and dermis have evolved several innate strategies to
      prevent infection. Antimicrobial peptides are one of the primary mechanisms used
      by the skin in the early stages of immune defense. In general, antimicrobial
      peptides have broad antibacterial activity against gram-positive and negative
      bacteria and also show antifungal and antiviral activity. The antimicrobial
      activity of most peptides occurs as a result of unique structural characteristics
      that enable them to disrupt the microbial membrane while leaving human cell
      membranes intact. However, antimicrobial peptides also act on host cells to
      stimulate cytokine production, cell migration, proliferation, maturation, and
      extracellular matrix synthesis. The production by human skin of antimicrobial
      peptides such as defensins and cathelicidins occurs constitutively but also
      greatly increases after infection, inflammation or injury. Some skin diseases
      show altered expression of antimicrobial peptides, partially explaining the
      pathophysiology of these diseases. Thus, current research suggests that
      understanding how antimicrobial peptides modify susceptibility to microbes,
      influence skin inflammation, and modify wound healing, provides greater insight
      into the pathophysiology of skin disorders and offers new therapeutic
      opportunities.

PMID- 18086588
TI  - CD30 expression on CD1a+ and CD8+ cells in atopic dermatitis and correlation with
      disease severity.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with
      cutaneous hyperreactivity to environmental stimuli, resulting in increased
      infiltration of inflammatory cells, IgE production and enhanced expression of
      costimulatory molecules, cytokines and chemokines. CD30, a TNF receptor
      superfamily member, is a costimulatory molecule expressed on activated T and B
      cells. A positive correlation between soluble CD30 (sCD30) levels in patient
      serum and AD disease severity has been described previously. However, the
      relative frequencies and identities of cells expressing CD30 in AD patients and
      the relationship between the frequency of CD30 positive cells and serum sCD30
      levels with disease severity remained unknown. To address these questions,
      immunofluorescence analysis of AD skin lesions representing different disease
      stages, was conducted. In addition to the CD4+ T cells, CD1a+ Langerhans cells
      and CD8+ T cells were found to express CD30 in AD lesions and the cell numbers
      correlated with disease severity. FACS analysis of AD patient blood samples
      revealed expression of CD30 on memory T-cells and a correlation with disease
      severity was identified. Finally, serum analysis of soluble mediators revealed
      positive correlations between sCD30, IgE, MDC, TARC and PARC levels with disease
      severity. Combined, our data provide correlative evidence that CD30+ cells,
      including Langerhans cells and CD8+ T-cells, may contribute to AD disease
      severity and that therapeutic strategies targeting CD30+ cells may provide
      benefit to AD patients.

PMID- 18086590
TI  - The effectiveness of PUVA treatment in severe psoriasis is significantly
      increased by additional UV 308-nm excimer laser sessions.
AB  - In most cases, patients with moderate to severe psoriasis are treated with narrow
      band UVB phototherapy or with psoralen UVA (PUVA-) photochemotherapy. This UV
      radiation is given to the whole skin, including unaffected skin. Normally, these
      two PUVA- and UVB-radiation procedures cannot be combined on account of the
      phototherapeutic side-effects on unaffected skin. The 308-nm excimer laser has
      been shown to be safe and effective in the treatment of localized mild-to
      moderate plaque-type psoriasis whilst sparing healthy skin. Our aim was to
      compare the therapeutic response to PUVA plus up to 4 UVB308-nm radiations and
      PUVA monotherapy in patients with moderate-severe plaque-type psoriasis. 272
      hospitalized adult patients were enrolled on this prospective random study. 256
      patients completed the full course of treatment. PUVA treatment was given 4 times
      weekly to all patients. 123 patients received PUVA as a monotherapy. During the
      first two weeks, 149 patients were additionally treated up to four times with 308
      nm excimer-derived UVB on the affected skin and treatment was evaluated for its
      efficacy, duration, number of times necessary for complete (CR) or partial
      remission (PASI reduction > 90 or > 50%, respectively), cumulative light dose,
      side effects of therapy and duration of remission after therapy. Statistically,
      there is no significant difference when comparing the efficacy of PUVA (CR 67.3%)
      and PUVA plus excimer (CR 63.6%). On average, patients treated by the combination
      method went into remission in half the treatment time (15 +/- 6 versus 27 +/- 7
      days) and with half the cumulative UVA dose (22.9 +/- 5.8 versus 53.2 +/- 26.3),
      p < 0.05. In conclusion, skin heals considerably quicker when treated with a
      combination of photochemotherapy and a short course of UVB 308 nm laser treatment
      applied directly to the affected skin, resulting in a shorter hospital stay and
      quicker rehabilitation of patients with moderate-severe psoriasis.

PMID- 18086589
TI  - Expression of CD1a and CD86 on scleroderma Langerhans cells.
AB  - Scleroderma is a chronic autoimmune connective tissue disorder of unknown
      etiology that affects the microvasculature and loose connective tissue.
      Langerhans cells play an important role in the immune system of the skin. By
      immunohistochemistry we investigated the phenotypical characteristics of
      epidermal and dermal Langerhans cells and their spatial relationship with
      infiltrating lymphocytes in systemic scleroderma (SSc) and localized scleroderma.
      Skin samples were obtained from patients by 6 mm punch biopsy. Samples were
      stained with antibodies against CD1a and CD86. The number of cells stained with
      both antibodies in the dermal and epidermal infiltration was calculated. In
      contrast to normal skin, both types of scleroderma skin showed a marked increase
      in CD1a+ dermal Langerhans cells, whereas the number of CD1a+ cells in localized
      scleroderma was much higher than that in SSc (p < 0.05) either in the dermis or
      in the epidermis. The expression of CD86 was increased in the dermis of localized
      scleroderma compared with that in SSc or normal skin (p < 0.05). This study
      revealed that Langerhans cells may play an important role in the pathogenesis of
      scleroderma, especially in localized scleroderma. CD86 is predominantly expressed
      on dermal Langerhans cells in the lesional skin of localized scleroderma.
      Therefore, it might play an important role in the pathogenesis of localized
      scleroderma.

PMID- 18086591
TI  - Cutaneous sporotrichosis. Intermittent treatment (pulses) with itraconazole.
AB  - Sporotrichosis is a subcutaneous and exceptionally deep mycosis caused by a
      dimorphic fungus, Sporothrix schenckii. Itraconazole is a triazole derivative
      leading to good results in the treatment of sporotrichosis. Patients with
      cutaneous sporotrichosis proven with mycological tests (direct examination and
      culture) were enrolled. All patients underwent laboratory tests (at baseline and
      on a monthly basis) and received oral itraconazole 400 mg/day for one week with a
      3-week break (pulses); thereafter the drug was administered as pulses until
      clinical and mycological cure was achieved. Five patients with sporotrichosis
      were enrolled, 4 with cutaneous lymphangitic form and one with fixed cutaneous
      form. Clinical and mycological cure was achieved in 4/5 cases (80%), with a mean
      number of pulses of 3.5. No patient had side effects and no laboratory test
      abnormalities occurred. Intermittent or pulsed itraconazole was effective in
      treating cutaneous sporotrichosis. It may be considered as a new treatment choice
      that entails an important reduction in total medication use.

PMID- 18086592
TI  - A 4-month, open-label study evaluating the efficacy of eflornithine 11.5% cream
      in the treatment of unwanted facial hair in women using TrichoScan.
AB  - Eflornithine 11.5% cream is an effective treatment for unwanted facial hair (UFH)
      in women with the effect on facial hair growth starting to be seen from 1 month
      after treatment initiation. TrichoScan is a validated method of assessing hair
      length, thickness, density, and growth rate using contact skin microscopy. The
      study aimed to evaluate the efficacy of eflornithine cream in women with UFH, as
      assessed by TrichoScan. In this open-label, single-centre study, 25 women (aged
      25-63 years) applied eflornithine 11.5% cream to the upper lip twice daily for 4
      months. Hair density, mean and cumulative hair length, mean hair thickness and
      hair growth rate were assessed at baseline and Month 1, 2 and 4 using TrichoScan.
      Eflornithine cream significantly decreased hair density from baseline to Month 1
      (- 11.4 hairs/cm2, p = 0.014), Month 2 (- 16.5 hairs/cm2, p = 0.013) and Month 4
      (- 12.05 hairs/cm2, p = 0.05). In addition, cumulative hair length decreased from
      baseline to Month 1 (- 7.104 mm, p = 0.001), Month 2 (- 10.054 mm, p < 0.001) and
      Month 4 (- 8.061 mm, p = 0.001). There was also a significant decrease in hair
      growth rate. Mean hair thickness did not change significantly. Eflornithine 11.5%
      cream is an effective treatment for UFH in women with the effect on facial hair
      growth starting to be seen from 1 month after treatment initiation.

PMID- 18086593
TI  - Infliximab in recalcitrant generalized pustular arthropatic psoriasis.
AB  - Generalized pustular psoriasis is an unstable inflammatory type of psoriasis,
      with widespread areas of erythema and sterile pustules, associated with fever and
      systemic symptoms. Infliximab is a monoclonal antibody with anti-TNFalpha
      activity, approved for use in psoriasis. We describe a male patient with a long
      history of stable arthropathic psoriasis, hospitalized with a generalized
      pustular psoriasis and acute exacerbation of articular complaints. The disease
      was resistant to multiple therapies (acitretin, methotrexate and
      corticosteroids), so the patient was started on infliximab, with a very rapid
      response of both cutaneous and articular symptoms. He had complete clearing of
      lesions at week 12, and marked improvement of the articular symptoms. No
      recurrence occurred at 8 months of follow-up with infliximab every 8 weeks.
      Infliximab had an extremely rapid therapeutic action response on a recalcitrant
      generalized pustular psoriasis. The articular response was also excellent, with
      significant improvement of quality of life.

PMID- 18086594
TI  - Leukocyte common antigen-negative, aggressive cutaneous anaplastic large cell
      lymphoma with prominent pseudocarcinomatous hyperplasia.
AB  - Patients with anaplastic large cell lymphoma (ALCL) often present with tumor
      mediated skin changes, including pseudocarcinomatous hyperplasia (PCH), acquired
      ichthyosis, and tissue neutrophilia. We report a 58-year-old male patient with
      leukocyte common antigen (LCA)-negative, null cell-type ALCL associated with
      marked PCH mimicking undifferentiated squamous cell carcinoma. Although
      lymphocyte markers were lacking, the CD30 expression and the clonal rearrangement
      of the T-cell receptor gamma gene confirmed the diagnosis of ALCL. The patient
      had an aggressive clinical course, in which the tumor cells metastasized to the
      regional lymph nodes a few months after surgical removal of the primary lesion,
      and skin nodules recurred on the face despite intensive polychemotherapy,
      followed by autologous peripheral blood stem cell transplantation. The diagnosis
      of ALCL was delayed in our case because of the prominent PCH, the lack of LCA,
      and the unusually rapid progression of the tumor.

PMID- 18086595
TI  - Scleromyxedema diagnosis following unexplained encephalopathy.

PMID- 18086596
TI  - Linear atrophoderma of Moulin.

PMID- 18086597
TI  - Demographic and clinical features of Kaposi's sarcoma in thirty seven cases: a
      single center report from Turkey.

PMID- 18086598
TI  - Infantile myofibromatosis of the scrotum.

PMID- 18086600
TI  - Acquired reactive perforating collagenosis induced by indinavir in 2 patients
      with HIV disease.

PMID- 18086599
TI  - The "COMMA-flap": a new technique for inner canthus reconstruction.

PMID- 18086601
TI  - Gabapentin for the treatment of recalcitrant chronic prurigo nodularis.

PMID- 18086602
TI  - Craniofacial hyperhidrosis successfully treated with botulinum toxin type A.

PMID- 18086603
TI  - Dermatitis herpetiformis in a patient receiving infliximab for ankylosing
      spondylitis.

PMID- 18086604
TI  - Lichenoid type of cutaneous sarcoidosis: great response to topical tacrolimus.

PMID- 18086606
TI  - Treatment of palmoplantar pustular psoriasis with efalizumab: a quick response
      with early recurrence.

PMID- 18086605
TI  - Oncocerchiasis: an imported case from the tropics.

PMID- 18086607
TI  - Immunohistochemical analysis of the immune cells in the epithelioid cell
      granuloma of tuberculoid leprosy.

PMID- 18086608
TI  - Waterproof camouflage age for vitiligo of the face using Cavilon 3M as a spray.

PMID- 18086609
TI  - Atopy in patients with recurrent apthouse stomatitis.

PMID- 18086610
TI  - Folie a deux, diagnosed by delusional parasitosis.

PMID- 18086611
TI  - Piroxicam-induced fixed drug eruption.

PMID- 18086612
TI  - Pyoderma gangrenosum of the scalp following hair highlights in a postpartum
      patient.

PMID- 18086613
TI  - Pigmented dermatofibrosarcoma protuberance (Bednar tumor).

PMID- 18086614
TI  - Angiokeratoma and epidermal nevus.

PMID- 18086615
TI  - Zosteriform cutaneous localizations of B-cell chronic lymphocytic leukaemia.

PMID- 18086616
TI  - X-linked reticulate pigmentary disorder: report of a new family.

PMID- 18086617
TI  - Purpura and ecchymosis under carbamazepine, chloral hydrate and melitracen
      flupentixol.

PMID- 18086618
TI  - Skin diseases with high public health impact. Urticaria and angioedema.

PMID- 18086619
TI  - Damage control surgery for severe pancreatic trauma.

PMID- 18086620
TI  - Metabolic syndrome and non-alcoholic fatty liver disease: Asian definitions and
      Asian studies.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally
      recognized, is a metabolic disorder largely confined to residents of affluent
      industrialized Western countries. However, obesity and insulin resistance are not
      restricted to the West, as witnessed by their increasingly universal
      distribution. In particular, there has been an upsurge in metabolic syndrome in
      the Asia-Pacific region, although there are critical differences in the extent of
      adiposity between Eastern and Western populations. DATA SOURCES: An English
      language literature search using PubMed (1999-2007) on obesity, metabolic
      syndrome and NAFLD, focusing on Asian definitions and Asian studies. RESULTS:
      NAFLD appears to be of long-standing insulin resistance and likely represents the
      hepatic manifestation of the metabolic syndrome. With insulin resistance as a
      common factor, the disease is associated with atherosclerosis and cardiovascular
      risk. All features of the metabolic syndrome and related events are assessed for
      practical management of NAFLD, although the criteria for the diagnosis of obesity
      and central obesity differ across racial groups. CONCLUSIONS: The increasing
      prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension and
      ultimately metabolic syndrome, puts a very large population at risk of developing
      NAFLD in the coming decades. The simultaneous identification and appropriate
      treatment of the components of metabolic syndrome are crucial to reduce hepatic
      as well as cardiovascular morbidity and mortality.

PMID- 18086621
TI  - Clinical studies on inferior right hepatic veins.
AB  - BACKGROUND: Many small veins are called accessory, short hepatic veins in
      addition to the right, middle and left hepatic veins. The size of these veins
      varied from a pinhole to 1 cm; the size of inferior right hepatic veins (IRHVs)
      is thicker than that of short hepatic veins or more than 1 cm occasionally.
      Adults have a higher incidence rate of the IRHV. DATA SOURCES: A literature
      search of the PubMed database was conducted and research articles were reviewed.
      RESULTS: The size of IRHVs is related to the size of the right hepatic vein, i.e.
      the larger the diameter of the right hepatic vein, the smaller the diameter of
      the IRHVs, and vice versa. The IRHVs are divided into superior, medial and
      inferior groups, separately named the superior, medial and inferior right hepatic
      veins according to the position of the IRHV entering the inferior vena cava. The
      superior right hepatic vein mainly drains the superior part of segment VII, and
      the medial right hepatic vein drains the middle part of segment VII. A thicker
      IRHV mainly drains segment VI and the inferior part of segment VII and a thinner
      IRHV drains the inferior part of segment V. CONCLUSIONS: The clinical
      significance of these studies on IRHVs is varied: (1) Hepatic caudate lobe
      resection could be introduced after study on the veins of that lobe. (2) It is
      very important to identify the draining region of the IRHV for guiding hepatic
      segmentectomy. The postero-inferior area of the right lobe can be preserved along
      with the hypertrophic IRHV even if the entire main right hepatic vein is resected
      during segmentectomy of VII and VIII with right hepatic vein resection for
      patients with primary liver cancer. (3) The ligation of the major hepatic vein
      for the treatment of juxtahepatic vein injury is recommended because of severe
      hemorrhagic shock and difficulty in exposure. (4) It is very helpful to decide
      therapeutic modalities for Budd-Chiari syndrome.

PMID- 18086622
TI  - Combined liver and kidney transplantation in Guangzhou, China.
AB  - BACKGROUND: When liver or kidney transplant can respectively cure end-stage liver
      or kidney disease, neither hepatic graft nor renal transplant alone can be used
      as a radical therapy for diseases which involve both liver and kidney. Combined
      liver and kidney transplantation commenced late in China, and the number of
      transplants has been limited. This study was designed to assess the effects of
      simultaneous combined liver and kidney transplantation (SLKT) on end-stage liver
      and kidney diseases. METHODS: Fifteen patients who had received SLKT from 1996 to
      2006 in the First Affiliated Hospital of Sun Yat-Sen University were reviewed.
      They included 5 patients with polycystic liver and kidney, 5 patients with
      hepatic cirrhosis and renal failure, and 5 patients with fulminant hepatic
      failure and hepatorenal syndrome (11 men and 4 women; average age 43.5 years).
      All patients had combined liver and kidney transplantation. RESULTS: The 5
      patients with polycystic liver and kidney have survived for more than one year
      after SLKT, and the longest survival has been 5 years. Three of the 5 patients
      with hepatic cirrhosis and renal failure have survived more than two years; one
      died perioperatively and the other died from recurrence of hepatitis B 18 months
      after the operation. Three of the 5 patients with fulminant hepatic failure and
      hepatorenal syndrome have survived for two years, and 2 died of multiple organ
      failure during the operation. CONCLUSIONS: SLKT is an effective therapy for end
      stage liver and kidney disease but the indications of SLKT for hepatorenal
      syndrome should be strict. SLKT may immunologically protect the renal graft.

PMID- 18086623
TI  - Measures for increasing the safety of donors in living donor liver
      transplantation using right lobe grafts.
AB  - BACKGROUND: The safety of donors in living donor liver transplantation (LDLT)
      should be the primary consideration. The aim of this study was to report our
      experience in increasing the safety of donors in LDLTs using right lobe grafts.
      METHODS: We retrospectively studied 37 living donors of right lobe grafts from
      January 2002 to March 2006. The measures for increasing the safety of donors in
      LDLT included carefully selected donors, preoperative evaluation by
      ultrasonography, angiography and computed tomography; and necessary
      intraoperative cholangiography and ultrasonography. Right lobe grafts were
      obtained using an ultrasonic dissector without inflow vascular occlusion on the
      right side of the middle hepatic vein. The standard liver volume and the ratio of
      left lobe volume to standard liver volume were calculated. RESULTS: There was no
      donor mortality in our group. Postoperative complications only included bile
      leakage (1 donor), biliary stricture (1) and portal vein thrombosis (1). All
      donors recovered well and resumed their previous occupations. In recipients,
      complications included acute rejection (2 patients), hepatic artery thrombosis
      (1), bile leakage (1), intestinal bleeding (1), left subphrenic abscess (1) and
      pulmonary infection (1). The mortality rate of recipients was 5.4% (2/37); one
      recipient with pulmonary infection died from multiple organ failure and another
      from occurrence of primary disease. CONCLUSIONS: The first consideration in adult
      to-adult LDLT is the safety of donors. The donation of a right lobe graft is safe
      for adults if the remnant hepatic vasculature and bile duct are ensured, and the
      volume of the remnant liver exceeds 35% of the total liver volume.

PMID- 18086624
TI  - The incidence of sporadic viral hepatitis in North India: a preliminary study.
AB  - BACKGROUND: Viral hepatitis is one of the major causes of mortality and morbidity
      in developing countries. Hepatitis E virus (HEV) among the major etiological
      agents is responsible for both sporadic and epidemic outbreaks. The epidemic
      outbreak is water-borne whereas the sporadic outbreak is possibly through
      contact. Various diagnostic tools at times fail to pinpoint the cause of viral
      hepatitis. This study was carried out to evaluate the utility of ELISA and nested
      reverse transcriptase polymerase chain reaction (nRT-PCR) for the diagnosis of
      sporadic and acute viral hepatitis (AVH) caused by HEV in an endemic situation in
      North India. METHODS: Serum samples were collected from all the affected and
      suspected persons and subjected to serological detection of HAV IgM, HBsAg, HCV
      antibody and HEV IgM. The samples that were positive for HEV IgM were further
      processed for the detection of HEV RNA by nRT-PCR. RESULTS: A total of 843
      samples were collected from 685 patients with AVH, 70 patients with fulminant
      hepatic failure (FHF), 53 patients with chronic liver disease (CLD), 11 patients
      with antituberculosis therapy (ATT)-induced jaundice, and 24 pregnant women. The
      percentage of positivity for anti-HEV IgM was 58.3% in the pregnant women, 41.4%
      in the patients with FHF, 38.6% in the patients with AVH, 9.4% in the patients
      with CLD and 18.2% in the patients with ATT induced jaundice. 9.4% of HBsAg
      carriers were positive for anti-HEV IgM. Males outnumbered females (62.8% vs.
      37.1%). Furthermore, the rates of fulminant and acute outbreaks of hepatitis with
      HEV RNA positivity were 41.4% and 9.4%, respectively. CONCLUSION: Serological and
      molecular analysis should be combined for the diagnosis of viral infections,
      especially in endemic areas.

PMID- 18086625
TI  - Long-term results of laparoscopic fenestration for patients with congenital liver
      cysts.
AB  - BACKGROUND: The feasibility and immediate outcome of laparoscopic fenestration
      for patients with congenital liver cysts have been generally recognized. The aim
      of the present study was to assess the long-term results after laparoscopic
      fenestration. METHODS: A retrospective study was performed on 44 patients with
      congenital liver cysts who had undergone laparoscopic fenestration between June
      1998 and December 2004. Among them, 30 were women and 14 men, aged 57 years on
      average (range 18-76 years). While 14 patients had solitary cysts, 20 had
      multiple cysts, and 10 had polycystic liver disease. The results of laparoscopic
      fenestration, including mortality, morbidity, mean postoperative hospital stay,
      and recurrences of cysts were evaluated. RESULTS: There was no perioperative
      death and the morbidity rate was 11% (5/44). All complications were treated
      conservatively. The mean postoperative hospital stay was 4 days. A mean follow-up
      of 57 months showed that the rates of cyst recurrence and symptom recurrence were
      9% and 4.5%, respectively. CONCLUSION: Laparoscopic fenestration as a feasible
      and safe treatment procedure for patients with congenital liver cysts can yield
      very good long-term results.

PMID- 18086626
TI  - Breviscapine alleviates hepatic injury and inhibits PKC-mRNA and its protein
      expression in brain-dead BA-Ma mini pigs.
AB  - BACKGROUND: Brain-dead donors are the main sources for organ transplantation, but
      many studies show that brain-death affects the organ's function after
      transplantation. This study was undertaken to investigate liver injury after
      brain-death in BA-Ma mini pigs and the protective effects of breviscapine on
      hepatic function and on PKC-alpha mRNA and its protein expression. METHODS:
      Fifteen BA-Ma mini pigs were equally divided into 3 groups at random: brain-dead
      (group B), breviscapine pretreated (group P), and control (group C). The brain
      dead model was established by increasing intracranial pressure in a modified,
      slow and intermittent way. At 3, 6, 12, 18 and 24 hours after the initial brain
      death, the levels of serum AST, ALT, TNF-alpha, IL-1beta, and IL-6 were
      determined. The changes in hepatic tissues were assessed, and the expression of
      PKC-alpha and PKC-alpha mRNA was detected by immunohistochemistry and RT-PCR,
      respectively. RESULTS: The levels of AST and ALT in groups B and P began to
      increase 12 hours after brain-death, while the values in group P were lower than
      those in group B (P<0.05). The levels of IL-1beta, IL-6, and TNF-alpha in groups
      B and P at 3, 6, 12 and 18 hours were lower than those in group B (P<0.05). At 6,
      12 and 24 hours, the expressions of PKC-alpha mRNA and PKC-alpha protein in group
      P were lower than those in group B (P<0.05). The degree of injury to hepatic
      cells in group P was milder than that in group B. CONCLUSIONS: Breviscapine
      inhibits the degree of PKC-alpha mRNA transcription and its protein translation,
      decreases the release of inflammatory factors, and thus alleviates hepatic injury
      during brain-death.

PMID- 18086627
TI  - Effect of fatty liver background on contrast-enhanced ultrasonographic appearance
      of focal nodular hyperplasia.
AB  - BACKGROUND: Focal nodular hyperplasia (FNH) is increasingly diagnosed as a result
      of the advances in imaging studies such as contrast-enhanced ultrasonography
      (CEUS), enhanced computed tomography and magnetic resonance imaging. However, FNH
      with atypical features can be difficult to differentiate from other benign and
      malignant tumors. The aim of this study was to investigate the influence of fatty
      liver background on the CEUS characteristics of FNH. METHODS: Twenty-six patients
      with FNH were divided into two groups: group A included 14 patients with fatty
      liver and group B included 12 patients with normal liver background. Conventional
      two-dimensional ultrasonography and color Doppler flow imaging (CDFI) were
      conducted and followed by real-time dual-frame CEUS. RESULTS: On two-dimensional
      ultrasonography, hypo-echoic nodules were present in most of the patients in
      group A (12/14) and hyperechoic nodules in most of those in group B (7/12). The
      difference in the nodule echotextures between the two groups was statistically
      significant (P<0.05). Nodules with centrifugal blood flow signals on CDFI were
      found in 6 of the 14 patients in group A and 5 of the 12 in group B (P>0.05). On
      CEUS, nodules with a central spoked-wheel-like enhancement pattern in the early
      arterial phase were observed in 8 patients in group A and those with an eccentric
      enhancement pattern in the remaining 6 patients. In this group, 3 patients had
      hypoechoic nodules in the delayed phase. Eleven of the 14 patients in this group
      were diagnosed accurately with CEUS. In group B, nodules with a rapid central
      spoked-wheel-like enhancement pattern in the early arterial phase were found in 8
      patients by CEUS and those with rapid an eccentric enhancement pattern in 4. The
      nodules were found to be continuously enhanced in the delayed phase. All of the
      patients in group B were accurately diagnosed with CEUS. CONCLUSIONS: A FNH
      nodule on a background of fatty liver may present a hypoechoic pattern on two
      dimensional ultrasonography and a hypoechoic wash-out pattern in the delayed
      phase on CEUS. At this time, punch biopsy is needed for the diagnosis or
      differential diagnosis of FNH.

PMID- 18086628
TI  - Dynamic expression of rat heat shock protein gp96 and its gene during development
      of hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by multicause,
      obvious multistage and multifocal processes of tumor progression. The development
      of HCC is related intimately to overexpression and signal transduction of many
      cellular factors. This study was undertaken to investigate the dynamic expression
      and alteration of heat shock protein (HSP) gp96 along with its gene during HCC
      development. METHODS: A rat model of hepatoma induced with 2-fluorenylacetamide
      (2-FAA, 0.05%) was established in male Sprague-Dawley rats. Total RNA and
      pathological changes were observed during hepatocarcinogenesis. Total RNAs were
      transcribed into cDNA by reverse transcription and the gene fragment of gp96 was
      amplified by nested RT-PCR. The gp96 expression in rat liver tissues was semi
      quantitatively analyzed by immunohistochemistry. RESULTS: Histological
      examination suggested that hepatocytes in rats fed with 2-FAA showed vacuole-like
      denaturation at the early stages, then dysplastic nodules appeared at the middle
      stage, and finally progressed to tubercles of cancerous nests. A tendency of
      increasing liver gp96 protein level was found from normal liver to precancerous
      to cancerous tissues during hepatoma development (P<0.01), and was in accordance
      with the changes in gp96 mRNA (P<0.05). CONCLUSION: HSP gp96 is involved in HCC
      development and its overexpression may be a useful marker for early diagnosis.

PMID- 18086629
TI  - Evaluation of surgical approach for extrahepatic cholangiocarcinoma.
AB  - BACKGROUND: The incidence of extrahepatic cholangiocarcinoma increases in recent
      years. But the diagnosis and treatment are still troublesome to surgeons. This
      study was designed to explore the value of surgical approach in the treatment of
      extrahepatic cholangiocarcinoma. METHODS: We retrospectively analyzed the
      clinical data of 135 patients with extrahepatic cholangiocarcinoma who had been
      treated in our hospital from January 1992 to December 2006. RESULTS: The ratio of
      extrahepatic cholangiocarcinoma to biliary duct diseases was 1.81%. The rates of
      total resection and radical resection were 70.75% (75/106) and 56.60% (60/106),
      respectively. The overall 1-, 3-, 5-year survival rates were 46.93%, 37.33% and
      18.75%, respectively. The 1-, 3-, 5-year survival rates were better in the
      radical resection group (74.94%, 55.74% and 41.27%, respectively) than in the
      palliative resection group (42.86%, 26.79% and 26.79%, respectively) (P<0.05).
      The survival rates of patients who had undergone palliative resection were higher
      than those of patients who had been subjected to palliative drainage or non
      operation: 1-, 3-, 5-year survival rates were 42.86%, 26.79%, 26.79% vs. 23.33%,
      6.67%, 0 or 17.86%, 0, 0 (P<0.05). While the survival rates were not
      significantly different between palliative drainage and non-operation (P<0.05).
      Multivariate analysis revealed that the histopathological grades, TNM stages and
      modalities were key factors influencing the outcome. CONCLUSIONS: The outcome of
      the patients with extrahepatic cholangiocarcinoma is still not optimistic.
      Radical resection is the first choice for the treatment of tumors.

PMID- 18086630
TI  - Possible relationship between cholecystectomy and subsequent occurrence of
      primary common bile duct stones: a retrospective review of data.
AB  - BACKGROUND: Most reports on the prognosis of cholecystectomy have been short-term
      studied, and few long-term reports have suggested variable incidences of common
      bile duct stones after cholecystectomy. We retrospectively reviewed the data to
      find the possible association between cholecystectomy and the subsequent
      occurrence of primary common bile duct stones. METHODS: The data were reviewed
      retrospectively of 478 patients with primary common bile duct stones diagnosed
      and treated by endoscopic sphincterotomy at our hospitals between January 1994
      and December 2003. RESULTS: Sixty-one (14.1%) of the 432 patients had a history
      of cholecystectomy, with an incidence rate markedly higher than that in the
      general population. The mean interval between cholecystectomy and the occurrence
      of primary common bile duct stones was 8.23 years, with the longest being 28
      years and the shortest 2 years. Compared with the patients who had not undergone
      a prior cholecystectomy, those who had had a prior cholecystectomy more often
      accompanied with acute cholangiolitis (chi(2)=8.259, P<0.01), and multiple stones
      or sand-like stones were frequently found (chi(2)=9.030, P<0.01). CONCLUSIONS:
      These results suggest a possible relationship between cholecystectomy and the
      subsequent occurrence of primary common bile duct stones. Perhaps patients with
      primary common bile duct stones who have had a prior cholecystectomy have a
      higher probability of infection of the biliary system. The infection may be one
      of the causes of occurrence of primary common bile duct stones after
      cholecystectomy.

PMID- 18086631
TI  - Diagnosis and surgical treatment of hepatic hilar cholangiocarcinoma.
AB  - BACKGROUND: Hepatic hilar cholangiocarcinoma can be diagnosed early with the
      progress in diagnostic imaging, and thus the rate of resection of the tumor has
      increased markedly. To assess the effectiveness of resection, we reviewed 185
      cases of hepatic hilar cholangiocarcinoma diagnosed and treated at our hospital.
      METHODS: The clinical data of 185 patients with hepatic hilar cholangiocarcinoma
      who had been treated surgically from 1972 to 2006 were retrospectively analyzed.
      RESULTS: The records of the 185 patients were divided into first stage (1972
      1986) or second stage (1987-2006) according to the incidence of the tumor and its
      resection rate. Primary symptoms included upper abdominal discomfort or pain,
      anorexia, tiredness, weight loss and progressive jaundice. Ultrasonography,
      computed tomography (CT), magnetic resonance imaging (MRI), and magnetic
      resonance cholangiopancreatography (MRCP) were first line methods for atraumatic
      diagnosis. If the patients displayed intrahepatic bile duct dilatation or were
      diagnosed as suffering from extrahepatic obstructive jaundice, percutaneous
      transhepatic cholangiography (PTC), MRCP or endoscopic retrograde
      cholangiopancreatography (ERCP) should be used. In this series, 87 patients
      underwent resection of the tumor (47.0%). Of the 87 patients, 43 received radical
      resection and 44 palliative resection. Fifteen patients underwent resection in
      the first stage and 72 in the second stage. A total of 74 patients were followed
      up after the resection. The median survival time of the radical resection group
      was 37 months and that of the palliative resection group was 17 months (P<0.001).
      The other 62 patients receiving no resection died within 1.5 years. CONCLUSIONS:
      Once patients are diagnosed with hepatic hilar cholangiocarcinoma, they should
      undergo exploratory laparotomy. Resection is the most effective method for the
      treatment of hepatic hilar cholangiocarcinoma.

PMID- 18086632
TI  - Downregulation of AQP2 and AQP2 mRNA expression in kidney medulla of rats with
      bile duct ligation.
AB  - BACKGROUND: Obstructive jaundice is a common disease. Acute renal injury,
      secondary to obstructive jaundice, is one of the main causes of postoperative
      multiple system failure. This investigation evaluated renal function and renal
      aquaporin 2 (AQP2) expression changes in obstructive jaundice. METHODS: Forty
      male Wistar rats were equally randomized into two groups. Twenty in the
      obstructive jaundice group were subjected to common bile duct ligation, and then
      were subdivided into 7- and 14-day obstruction groups, and the other 20 sham
      operated rats were also subdivided into 7- and 14-day groups. At the end of each
      experiment, rats were sacrificed, venous blood was collected from the inferior
      vena cava, and serum creatinine and urine nitrogen concentrations were measured.
      At the same time, the medulla of the right kidney was separated and AQP2
      expression was assessed. The RT-PCR technique was used to detect AQP2 mRNA
      expression. RESULTS: Ligation of the common bile duct caused significant rises in
      serum bilirubin, creatinine clearance and urine nitrogen. AQP2 expression in the
      medulla decreased mere significantly (38.35+/-2.08) in the 7-day ligation group
      than in the sham-operated group (41.06+/-1.04), as did that in the 14-day
      ligation group, even more than (31.89+/-1.57). The expression of AQP2 mRNA also
      decreased more significantly in the 14-day group (0.5429+/-0.1107) than in the 7
      day group (0.6071+/-0.1328). CONCLUSION: AQP2 expression is inhibited in
      obstructive jaundice, and so is its gene expression.

PMID- 18086633
TI  - Combined detection of serum tumor markers for differential diagnosis of solid
      lesions located at the pancreatic head.
AB  - BACKGROUND: The differential diagnosis of solid lesions located at the pancreatic
      head is very important for choosing therapies and setting up surgical tactics.
      This study was designed to evaluate the clinical significance of combined
      measurement of multiple serum tumor markers and the application of the receiver
      operating characteristic (ROC) curves in the differential diagnosis of solid
      lesions located at the pancreatic head. METHODS: The serum levels of CA19-9,
      CA242, CA50 and carcinoembryonic antigen (CEA) in 112 patients with carcinoma of
      the pancreatic head and 38 patients with focal chronic pancreatitis in the
      pancreatic head were measured with ELISA. The sensitivity, specificity, positive
      likelihood ratio (PLR) and negative likelihood ratio (NLR) of the four serum
      tumor markers were calculated. The ROC curves for the four serum tumor markers
      were constructed and the area under the curve (AUC) was calculated. RESULTS: The
      AUCs of CA19-9, CA242, CA50 and CEA were 0.805, 0.749, 0.738 and 0.705; the PLRs
      were 1.91, 3.43, 5.09 and 5.46; and the NLRs were 0.41, 0.56, 0.59 and 0.71,
      respectively. Combined measurements increased the diagnostic specificity, and
      parallel combined testing increased the diagnostic sensitivity. CONCLUSIONS:
      Combined measurement of serum tumor markers CA19-9, CA242, CA50 and CEA is
      valuable in differential diagnosis of solid lesions located at the pancreatic
      head, and CA19-9 has the best diagnostic ability. Combined measurements can
      increase the specificity of diagnosis. Evaluation with the ROC curve is better
      than the sensitivity or specificity alone and the results are more integrated and
      objective.

PMID- 18086634
TI  - Low-dose dopamine reduces inflammatory factors of acute pancreatitis in rats.
AB  - BACKGROUND: Acute pancreatitis, especially acute necrotizing pancreatitis (ANP),
      is a serious disease with a high morbidity because of multiorgan dysfunction.
      Recent studies have indicated that during the pathogenesis of ANP, changes of the
      microcirculation play an important role in the worsening of the disease. This
      study based on a model of acute pancreatitis in Wistar rats was to determine the
      effect of treatment with low-dose dopamine on acute pancreatitis by the dynamic
      measurement of serum levels of inflammatory factors IL-6 and TNF-alpha. METHODS:
      Fifty Wistar rats were randomly divided into two groups, and a model of ANP was
      set up by injecting sodium taurocholate into the pancreatic duct. Rats in the
      dopamine group (treatment group) were given dopamine by vein and those in the
      acute pancreatitis group (control group) were given normal saline. To assess the
      effect of low-dose dopamine (5 mug.kg-1.min-1) on induced acute pancreatitis, the
      antibody sandwich ELISA method was used to measure the serum levels of IL-6 and
      TNF-alpha at different times before and after the induction of ANP. RESULTS: The
      serum levels of IL-6 and TNF-alpha in the treatment and control groups before and
      after ANP induction were significantly different. There was a markedly
      significant difference in the comparison of the two groups after ANP induction
      (P<0.01), but no significant difference in the comparison before the induction
      (P>0.05). Postoperative pancreatic histopathologic changes in the treatment group
      were more marked than those in the control group. CONCLUSIONS: Low-dose dopamine
      is effective in treating ANP by alleviating inflammatory reactions. This effect
      may be related to the fact that low-dose dopamine not only can increase the blood
      flow of the pancreatic microcirculation but also reduce its permeability.

PMID- 18086635
TI  - Metastasis of hepatocellular carcinoma to Virchow's node: have the tumor cells
      gone astray?
AB  - BACKGROUND: Virchow's node is a common site for metastasis in cancers of the
      stomach and pancreas. It is rarely involved in hepatocellular carcinoma. METHOD:
      We report on a patient with hepatoma who had metastasis to the left
      supraclavicular node at presentation. RESULTS: This 25-year-old man presented
      with abdominal pain, fever, weight loss, hard nodular hepatomegaly and a hard,
      fixed left supraclavicular lymphadenopathy. He was hepatitis B surface antigen
      positive, had elevated serum alpha-fetoprotein levels, and transabdominal imaging
      showed a space-occupying lesion in the right lobe of the liver. Fine needle
      aspiration of the left supraclavicular node revealed a poorly differentiated
      carcinoma. CONCLUSION: Metastasis to the Virchow-Trosier node in hepatoma,
      although uncommon, can occur probably via the hepatic node and then through the
      thoracic duct.

PMID- 18086636
TI  - Cholesterol crystal embolism leading to perforation of the gallbladder.
AB  - BACKGROUND: Cholesterol crystal embolism (CCE) from atherosclerotic arterial
      disease leading to perforation of the gallbladder is rare. We describe our
      experience of managing a patient with perforation of gallbladder caused by CCE.
      METHODS: A 64-year-old man was admitted to this hospital because of acute
      abdominal pain with clinical features suggestive of peritonitis. He was known to
      suffer from atherosclerotic peripheral arterial disease and had undergone
      aortobifemoral bypass 17 years ago. A CT scan showed a collection of peri-hepatic
      fluid. The gallbladder was normal in appearance but contained multiple calculi.
      At laparotomy, free bile was observed in the peritoneal cavity, leaking from a
      pin-hole size peroration of the fundus of the gallbladder. Hence cholecystectomy
      was performed. RESULTS: The patient made an uneventful recovery. Histological
      study of the gallbladder showed chronic cholecystitis and obliteration of the
      lumen of the mural arteries with cholesterol crystals within, indicating CCE.
      CONCLUSIONS: Although perforation of the gallbladder following CCE of its mural
      arteries is rare, the diagnosis should be considered in patients with abdominal
      pain and known atherosclerotic arterial disease. Management should include an
      early recognition of this condition, prompt institution of treatment, prevention
      of further insults by discontinuing or avoiding predisposing factors, and
      modification of cardiovascular risk factors.

PMID- 18086637
TI  - Combined hepatocellular carcinoma and cholangiocarcinoma: a case report and
      review of the literature.
AB  - BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is
      a rare histopathologic form of primary liver cancer. We report a case of cHCC-CC
      and review the literature. METHOD: The clinicopathological features of a 61-year
      old male were retrospectively analyzed. RESULTS: Hepatocellular carcinoma (HCC)
      was preoperatively considered on the basis of clinical findings resembling those
      associated with HCC. Hepatectomy was therefore performed. Microscopically, the
      specimen displayed histological features of cHCC-CC. The patient has remained
      alive after follow-up for 3 months without evidence of recurrence and metastasis.
      CONCLUSION: It is difficult to make a correct preoperative diagnosis of cHCC-CC
      and hepatic resection is the treatment of choice.

PMID- 18086638
TI  - Planning for a pandemic influenza outbreak: roles for librarian liaisons in
      emergency delivery of educational programs.
AB  - In February 2006, two librarians at the University of Minnesota's Bio-Medical
      Library were asked to participate in a task force at the University of
      Minnesota's School of Public Health (SPH). The charge from the dean of SPH was to
      determine how the school could continue to deliver its educational programs in
      the event of a pandemic influenza outbreak. This paper will outline the work of
      the task force, discuss its recommendations, and offer ideas on how other
      librarians can work with their liaison areas to plan for a similar project.

PMID- 18086639
TI  - The personal librarian program: an evaluation of a Cushing/Whitney Medical
      Library outreach initiative.
AB  - The Cushing/Whitney Medical Library (CWML) at the Yale School of Medicine has
      offered a "Personal Librarian" (PL) program to medical center students since
      1996. This outreach program matches students to a professional librarian as they
      matriculate, a relationship that is maintained until the student graduates. PLs
      offer individualized assistance for almost anything-from interpreting library
      policies and procedures to helping locate materials to assisting with thesis
      research. The program requires nominal effort on the part of the librarians,
      making it possible to expand the program to include other student groups. A
      recent survey revealed that students are extremely satisfied with the program and
      would generally welcome more contact from their PL.

PMID- 18086640
TI  - Migration to an electronic journal collection in a hospital library: implications
      for reference service.
AB  - This article provides a perspective on the migration to an electronic-only
      journal collection in a hospital library and its effect on reference services,
      information-seeking, and library use patterns. Bellevue Hospital Center in New
      York, NY is one of the first major teaching hospitals in the United States to
      begin a fundamental shift to a current, electronic-only journal collection. This
      article describes the process and develops a model for use by other hospital
      libraries, with commentary on the impact on reference services to library users.
      Key findings are that physicians, residents, and nurses have come to expect
      electronic journal collections and use the Internet in the hospital library to
      access electronic journals. Similar to many academic health sciences libraries,
      the reference desk in a hospital library has become more like a technical support
      desk. Users who contact the library have questions about access to the library's
      electronic resources or about searching techniques. In the future, medical
      reference librarians will continue to assist searchers who cannot find what they
      are looking for and will assist those who repeatedly get results that do not
      match their information needs.

PMID- 18086641
TI  - Library support for problem-based learning: an algorithmic approach.
AB  - Academic health sciences libraries can take various approaches to support the
      problem-based learning component of the curriculum. This article presents one
      such approach taken to integrate information navigation skills into the small
      group discussion part of the Pathophysiology course in the second year of the
      Dental school curriculum. Along with presenting general resources for the course,
      the Library Toolkit introduced an algorithmic approach to finding answers to
      sample clinical case questions. While elements of Evidence-Based Practice were
      introduced, the emphasis was on teaching students to navigate relevant resources
      and apply various database search techniques to find answers to the clinical
      problems presented.

PMID- 18086642
TI  - ISI web of knowledge: new author searching capability and reports features.
AB  - The Institute for Scientific Information (ISI), part of Thompson Scientific,
      produces the Web of Science database as part of its Web of Knowledge. Recently,
      ISI introduced some new features, among them a new Author Finder feature, which
      allows users to zero in on a specific author in a very guided way. In addition,
      search results may be analyzed and reports created by users, both at the click of
      a button. This column focuses on these recently introduced features.

PMID- 18086643
TI  - Navigating pitfalls of web-based survey development and administration.
AB  - With multiple low-cost Web-based delivery methods increasingly available, the
      number of surveys being distributed to gather data on library users and potential
      users is dramatically increasing. This paper provides an overview of survey
      administration including history, guidelines on decision-making in survey
      development, and best practices for survey research when delivered via the Web.
      Questions on survey development issues such as probability and non-probability
      sampling and privacy concerns are clarified.

PMID- 18086644
TI  - Experience and outcomes of medical librarian rounding.
AB  - This article highlights the positive results that can be achieved when a medical
      librarian rounds with a community hospital's Multidisciplinary Rounds (MDR) team.
      Background is provided on the rounding process on the hospital's Intensive Care
      Unit, and case studies report outcomes of the librarian's research. Noteworthy
      are changes in protocols and changes in patient care which were implemented
      based, in part, on studies supplied by the librarian.

PMID- 18086645
TI  - MRSQ Informatics Education columns: past, present and future.
AB  - This is the last Informatics Education column under the current editors. The
      outgoing editors identify six key themes that reflect the changes in informatics
      education over their seven-year tenure. The themes are picked from the 29
      previous columns published under their editorship. The first and key theme is
      technology, and this one theme is the basis for the other five. The incoming
      editors project what they expect to see as key themes for future columns.
      Together, this column looks at the past, present, and future state of informatics
      education in the United States.

PMID- 18086650
TI  - Summary of documented fatalities in livestock manure storage and handling
      facilities--1975-2004.
AB  - Data were compiled and analyzed on the estimated frequency and characteristics of
      deaths related to on-farm manure storage and handling facilities for the period
      of 1975 through 2004. Sources included published government reports, national and
      local media, on-line searches, published farm fatality reports, and prior
      litigation. No prior research was identified that addressed the magnitude of the
      problem, nor documented evidence-based intervention strategies. Data from 77
      fatalities along with 21 severe injuries and 14 international fatality cases were
      identified, documented and coded for analysis. Analysis of the 77 fatalities
      showed that victim characteristics and causative factors did not reflect
      previously reported patterns; i.e., over half of the fatalities involved dairy
      operations and 21% involved persons under the age of 16. The largest percentage
      (34%) of deaths occurred to persons conducting repair or maintenance activities
      on manure handling equipment, while the second largest group (22%) were
      attempting to perform a rescue of another person. The most frequently identified
      cause of death was asphyxiation with elevated levels of sulfide levels in the
      blood noted in some cases. The peak period of incidents were during the hottest
      part of the summer and often associated with transferring of manure for
      application to crop ground. Recommendations included the need to revise ASABE
      EP470 Manure Storage Safety Practice to include engineering controls that would
      reduce the need for farmers and farm workers to enter spaces containing toxic
      manure-related gases. In addition, the need to educate owner/operators and
      employees concerning the hazards associated with agricultural manure storage
      structures and equipment, especially those classified as permit-required confined
      spaces, should be considered, including the need for appropriate warnings and
      entry procedures. Incorporation of current OSHA confined space entry procedures
      into these facilities is also recommended.

PMID- 18086651
TI  - Assessing noise exposures in farm youths.
AB  - OBJECTIVE: This exploratory study evaluated the feasibility of field exposure
      assessment methods to characterize the noise sources and levels that farm youths
      experience during a typical workday. METHODS: Detailed exposure assessments were
      performed with a sample of 10 farm youths working on Vermont dairy farms to
      characterize potential noise hazards typical in the farm setting. Personal and
      area noise measurements were taken using noise dosimeters. Information concerning
      work- and non-work-related noise exposure histories was collected via
      questionnaire. RESULTS: The average age was 15.5 years (SD 2.5, range 10-18).
      Youths started working at an average age of 8.4 years (SD 2.3, range 6-12) and
      during the summer months worked an average of 41.3 hours per week (SD 32.3, range
      2-68). Two youths exceeded the OSHA action level, having eight-hour time-weighted
      averages of 95 dBA and 92 dBA, or alternatively, doses of 206% and 127%. (The
      OSHA action level for the hearing conservation amendment is an eight-hour time
      weighted average of 85 dBA or a dose of 50%.) Participants exceeding the action
      level reported working with tractors, skid steers (Bobcats), and all-terrain
      vehicles and doing general barn work. Additional sources of noise exposure
      included a mechanical silo elevator, chain saw, and wood splitter. CONCLUSION:
      Two of the monitored subjects were overexposed to noise in their farm work.
      Youths may be exposed to noise levels that exceed adult OSHA hearing conservation
      amendment action level as part of their daily farm activities.

PMID- 18086652
TI  - A pilot program using promotoras de salud to educate farmworker families about
      the risk from pesticide exposure.
AB  - This paper reviews a successful community-based education effort to minimize
      pesticide exposure to migrant and seasonal farmworkers and their families through
      innovative training curricula, informal participatory educational techniques and
      culturally sensitive outreach methods. In 2004, Migrant Clinicians Network, Inc.,
      trained lay health educators, or promotoras de salud, from local agencies in
      southern New Mexico in pesticide safety and in ways to successfully promote
      safety information in the farmworker community. Through home visits and small
      group workshops, the promotoras trained 273 farmworkers and farmworker family
      members on ways to reduce exposures to pesticides in their homes and at work,
      with an emphasis on protecting children. The families received a Spanish language
      comic book that reinforced the pesticide safety information, emphasizing the
      health effects of acute and chronic pesticide exposure and steps to protect
      farmworker children from pesticide exposure. The project resulted in a
      significant increase in knowledge regarding the routes of exposure, the
      vulnerability of children, the signs and symptoms of pesticide poisonings and the
      ways to minimize pesticide exposures. Additionally, the project showed improved
      behaviors aimed at minimizing pesticide exposure through accidental poisonings in
      the home. This pilot project proved the efficacy of an in-home, one-on-one
      approach with a culturally appropriate educational comic book as an instrument to
      help transfer education to the community. Moreover, the educational method
      involving promotoras offers a training-of- trainer approach that is easy to
      implement and potentially replicate.

PMID- 18086653
TI  - Cutaneous larva migrans in a migrant Latino farmworker.
AB  - Migrant farmworkers experience a high incidence of skin disease. This report
      provides information on the case history of cutaneous larva migrans in a Latino
      migrant farmworker. Treatment options are reviewed, and information for
      prevention is discussed.

PMID- 18086655
TI  - A task-based assessment of noise levels at a swine confinement.
AB  - This study describes a task-based noise evaluation conducted at a community
      college that operated a small swine confinement for training and profit. Seven
      full-shift dosimeter samples and area noise data were collected during the
      evaluation. The time weighted average noise levels were all well below the
      Occupational Safety and Health Administration's (OSHA) Permissible Exposure
      Limit, but exceeded the National Institute for Occupational Safety and Health's
      Recommended Exposure Limit on three of seven occasions. The potential for high
      noise exposures is evidenced in the noise dose measured for specific activities
      such as power washing, ear clipping, and snout snaring. When the data were
      extrapolated to depict exposures where specific tasks were carried out over a
      full shift, tasks such as power washing and snout snaring would exceed the OSHA
      Action Level (AL). Employees who exceed the OSHA AL are required to be enrolled
      in a hearing conservation program.

PMID- 18086654
TI  - Bronchodilator responsiveness in swine veterinarians.
AB  - OBJECTIVE: Swine veterinarians are known to be at risk for respiratory symptoms
      and airflow obstruction. The present study reassessed the prevalence of
      respiratory complaints and pulmonary function abnormalities in swine
      veterinarians and sought to characterize their response to bronchodilators.
      METHODS: A cross-sectional study was conducted during the American Association of
      Swine Veterinarians annual meeting. Subjects completed a respiratory symptom and
      workplace exposure history questionnaire and spirometry. Subjects with airflow
      obstruction were assessed for a post-bronchodilator response with beta2 agonist
      administration. RESULTS: Participants included 58 veterinarians (mean age, 45.5
      years). Work-related symptoms assessed by questionnaire included rhinitis
      symptoms (60.3%), cough and chest tightness (55.2%), and wheezing (35.1%).
      Airflow obstruction was detected in 11/58 (19%) of subjects by spirometry. Only
      2/9 (22.2%) met American Thoracic Society criteria for reversibility with
      bronchodilator administration. CONCLUSIONS: Respiratory symptoms and airway
      obstruction remain common findings in swine veterinarians. Airflow obstruction
      was not consistently reversible with beta agonists, suggesting that swine barn
      exposure may be a risk factor for irreversible airflow obstruction.

PMID- 18086659
TI  - Physical injuries caused by a transient loss of consciousness: main clinical
      characteristics of patients and diagnostic contribution of carotid sinus massage.
AB  - AIMS: To evaluate the prevalence and the characteristics of secondary trauma
      among patients referred to the emergency department (ED) for a transient loss of
      consciousness (TLOC). METHODS AND RESULTS: Over a 24 months period, all the
      patients referred to our ED for a TLOC were evaluated according to the ESC
      Guidelines on Syncope and enrolled in the study. Among 1253 consecutive patients
      with TLOC (1114 with a true syncope and 139 with a non-syncopal condition) 365
      (29.1%) reported a trauma, in 59 cases (4.7%) severe. The frequency and the
      characteristics of trauma did not differ among the two main categories of TLOC.
      Out of 54 patients with syncope and a severe trauma, 20 (37%) had a definite
      diagnosis after a guidelines-based initial evaluation, and further 17 (31.5%)
      during the hospital course. Among these latter, carotid sinus syndrome was by far
      the most common diagnosis. CONCLUSION: Among patients referred to the ED for a
      TLOC secondary trauma is a common complication, whose characteristics are of
      little utility to discover the specific cause of the symptom. For older patients
      with syncope complicated by a severe trauma carotid sinus massage should be the
      first diagnostic manoeuvre to be undertaken after a non-diagnostic initial
      evaluation.

PMID- 18086660
TI  - A double blind, randomized study on platelet aggregation in patients treated with
      a daily dose of 150 or 75 mg of clopidogrel for 30 days.

PMID- 18086661
TI  - Involvement of selective reactive oxygen species upstream of proapoptotic
      branches of unfolded protein response.
AB  - Cadmium triggers apoptosis of LLC-PK1 cells through induction of endoplasmic
      reticulum (ER) stress. We found that cadmium caused generation of reactive oxygen
      species (ROS) and that cadmium-induced ER stress was inhibited by antioxidants.
      In contrast, suppression of ER stress did not attenuate cadmium-triggered
      oxidative stress, suggesting that ER stress occurs downstream of oxidative
      stress. Exposure of the cells to either O(2)(*), H(2)O(2), or ONOO(-) caused
      apoptosis, whereas ER stress was induced only by O(2)(*) or ONOO(-). Transfection
      with manganese superoxide dismutase significantly attenuated cadmium-induced ER
      stress and apoptosis, whereas pharmacological inhibition of ONOO(-) was
      ineffective. Interestingly, transfection with catalase attenuated cadmium-induced
      apoptosis without affecting the level of ER stress. O(2)(*) caused activation of
      the activating transcription factor 6-CCAAT/enhancer-binding protein-homologous
      protein (CHOP) and the inositol-requiring ER-to-nucleus signal kinase 1-X-box
      binding protein 1 (XBP1) proapoptotic cascades, and overexpression of manganese
      superoxide dismutase attenuated cadmium-triggered induction of both pathways.
      Furthermore, phosphorylation of proapoptotic c-Jun N-terminal kinase by O(2)(*)
      or cadmium was suppressed by dominant-negative inhibition of XBP1. These data
      elucidated 1) cadmium caused ER stress via generation of ROS, 2) O(2)(*) was
      selectively involved in cadmium-triggered, ER stress-mediated apoptosis through
      activation of the activating transcription factor 6-CHOP and inositol-requiring
      ER-to-nucleus signal kinase 1-XBP1 pathways, and 3) phosphorylation of JNK was
      caused by O(2)(*)-triggered activation of XBP1.

PMID- 18086662
TI  - Suppression of v-Src transformation by andrographolide via degradation of the v
      Src protein and attenuation of the Erk signaling pathway.
AB  - Elevated expression and aberrant activation of the src oncogene are strongly
      associated with cancer initiation and progression, thereby making Src a promising
      molecular target for anti-cancer therapy. Through drug screening using a
      temperature-inducible v-Src-transformed epithelial cell line, we found that
      andrographolide could suppress v-Src-induced transformation and down-regulate v
      Src protein expression. In addition, actin cable dissolution and E-cadherin down
      regulation, features of transformed phenotype, are perturbed by andrographolide.
      Moreover, andrographolide promoted v-Src degradation via a ubiquitin-dependent
      manner. Although andrographolide treatment altered the tyrosine phosphorylation
      pattern in v-Src-expressing cells, it did not directly affect the kinase activity
      of v-Src. Both the Erk and phosphatidylinositol 3-kinase signaling pathways were
      strongly inhibited in andrographolide-treated v-Src cells. However, only MKK
      inhibitors (PD98059 and U0126) were able to cause a non-transformed morphology
      similar to that of andrographolide-treated v-Src cells. Moreover, overexpression
      of constitutively active MKK1 in v-Src cells blocked andrographolide-mediated
      morphological inhibition. Interestingly, andrographolide treatment could also
      reduce the protein level of the c-Src truncation mutant (Src531), an Src mutant
      originally identified from human colon cancer cells. In summary, we demonstrated
      that andrographolide antagonized v-Src action through promotion of v-Src protein
      degradation. Furthermore, attenuation of the Erk1/2 signaling pathway is
      essential for andrographolide-mediated inhibition of v-Src transformation. Our
      results demonstrate that andrographolide can act as a v-Src inhibitor and reveal
      a novel action mechanism of andrographolide.

PMID- 18086663
TI  - The circadian clock component BMAL1 is a critical regulator of p21WAF1/CIP1
      expression and hepatocyte proliferation.
AB  - Most living organisms show circadian (approximately 24 h) rhythms in physiology
      and behavior. These oscillations are generated by endogenous circadian clocks,
      present in virtually all cells where they control key biological processes.
      Although circadian gating of mitosis has been reported for many years in some
      peripheral tissues, the underlying molecular mechanisms have remained poorly
      understood. Here we show that the cell cycle inhibitor p21WAF1/CIP1 is
      rhythmically expressed in mouse peripheral organs. This rhythmic pattern of mRNA
      and protein expression was recapitulated in vitro in serum-shocked differentiated
      skeletal muscle cells. p21WAF1/CIP1 circadian expression is dramatically
      increased and no longer rhythmic in clock-deficient Bmal1-/- knock-out mice.
      Biochemical and genetic data show that oscillation of p21WAF1/CIP1 gene
      transcription is regulated by the antagonistic activities of the orphan nuclear
      receptors REV-ERBalpha/beta and RORalpha4/gamma, which are core clock regulators.
      Importantly, p21WAF1/CIP1 overexpressing Bmal1-/- primary hepatocytes exhibit a
      decreased proliferation rate. This phenotype could be reversed using small
      interfering RNA-mediated knockdown of p21WAF1/CIP1. These data establish a novel
      molecular link between clock and cell cycle genes and suggest that the G1
      progression phase is a target of the circadian clock during liver cell
      proliferation.

PMID- 18086664
TI  - Regulation and traffic of ceramide 1-phosphate produced by ceramide kinase:
      comparative analysis to glucosylceramide and sphingomyelin.
AB  - Ceramide 1-phosphate (C1P) has been characterized as a sphingolipid that
      participates in cell signaling. Although C1P synthesis is thought to occur via
      phosphorylation of ceramide by ceramide kinase (CerK), the processes that
      regulate C1P formation and fate remain largely unknown. In this study we analyzed
      bone marrow-derived macrophages (BMDM) from CerK-null mice (Cerk(-/-)) and found
      significant levels of C1P, suggesting that previously unrecognized pathways may
      also lead to C1P formation. After these experiments we used an overexpression
      system, BMDM from Cerk(-/-) mice, and short-chain fluorescent ceramides to trace
      CerK-dependent formation of C1P. Because the ceramide analogs can also be
      converted to glucosylceramide (GlcCer) and sphingomyelin (SM), they allowed us to
      directly compare all three metabolites. We found that C1P produced by CerK is
      turned over rapidly when serum is removed or upon calcium chelation, whereas
      GlcCer and SM are stable under these conditions. We further demonstrated that
      ceramide must be transported to the Golgi complex to be phosphorylated by CerK.
      Inhibition of the ceramide transfer protein slowed down SM formation without
      decreasing C1P, suggesting an alternate route of ceramide transport. Other
      experiments indicated that, like GlcCer and SM, C1P traffics along the secretory
      pathway to reach the plasma membrane. Furthermore, in BMDM C1P was secreted more
      readily than was GlcCer or SM. Altogether, our results indicate that CerK is
      essential to C1P formation via phosphorylation of Cer, providing the first
      insights into mechanisms underlying ceramide access to CerK and C1P trafficking
      as well as clarifying C1P as a signaling entity.

PMID- 18086665
TI  - Pet127 governs a 5' -> 3'-exonuclease important in maturation of apocytochrome b
      mRNA in Saccharomyces cerevisiae.
AB  - The details of mRNA maturation in Saccharomyces mitochondria are not well
      understood. All seven mRNAs are transcribed as part of multigenic units. The
      mRNAs are processed at a common 3'-dodecamer sequence, but the 5'-ends have seven
      different sequences. To investigate whether apocytochrome b (COB) mRNA is
      processed at the 5'-end from a longer precursor by an endonuclease or an
      exonuclease, a 64-nucleotide sequence, which is required for the protection of
      COB mRNA by the Cbp1 protein and is found at the 5'-end of the processed COB
      mRNA, was duplicated in tandem. The wild-type 64-nucleotide element functioned in
      either the upstream or downstream position when paired with a mutant element. In
      the tandem wild-type strain, the 5'-end of the mRNA was at the 5'-end of the
      upstream unit, demonstrating that the mRNA is processed by an exonuclease.
      Accumulation of precursor COB RNA in single and double element strains with a
      deletion of PET127 demonstrated that the encoded protein governs the 5'
      exonuclease responsible for processing the precursor to the mature form.

PMID- 18086666
TI  - Identification of an insulin-regulated lysophospholipase with homology to
      neuropathy target esterase.
AB  - Neuropathy target esterase (NTE) is a member of the family of patatin domain
      containing proteins and exhibits phospholipase activity in brain and cultured
      cells. NTE was originally identified as target enzyme for organophosphorus
      compounds that cause a delayed paralyzing syndrome with degeneration of nerve
      axons. Here we show that the structurally related murine protein NTE-related
      esterase (NRE) is a potent lysophospholipase. The enzyme efficiently hydrolyzes
      sn-1 esters in lysophosphatidylcholine and lysophosphatidic acid. No lipase
      activity was observed when triacylglycerols, cholesteryl esters, retinyl esters,
      phosphatidylcholine, or monoacylglycerol were used as substrates. Although NTE is
      predominantly expressed in the nervous system, we found the highest NRE mRNA
      levels in testes, skeletal muscle, cardiac muscle, and adipose tissue. Induction
      of NRE mRNA concentrations in these tissues during fasting suggested a
      nutritional regulation of enzyme expression and, in accordance with this
      observation, insulin reduced NRE mRNA levels in a dose-dependent manner in 3T3-L1
      adipocytes. A green fluorescent protein-NRE fusion protein colocalized to the
      endoplasmic reticulum and lipid droplets. Thus, NRE is a previously unrecognized
      ER- and lipid droplet-associated lysophospholipase. Regulation of enzyme
      expression by the nutritional status and insulin suggests a role of NRE in the
      catabolism of lipid precursors and/or mediators that affect energy metabolism in
      mammals.

PMID- 18086667
TI  - A balancing act between net uptake of water during dihydrofolate binding and net
      release of water upon NADPH binding in R67 dihydrofolate reductase.
AB  - R67 dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (DHF)
      to tetrahydrofolate using NADPH as a cofactor. This enzyme is a homotetramer
      possessing 222 symmetry, and a single active site pore traverses the length of
      the protein. A promiscuous binding surface can accommodate either DHF or NADPH,
      thus two nonproductive complexes can form (2NADPH or 2DHF) as well as a
      productive complex (NADPH.DHF). The role of water in binding was monitored using
      a number of different osmolytes. From isothermal titration calorimetry (ITC)
      studies, binding of NADPH is accompanied by the net release of 38 water
      molecules. In contrast, from both steady state kinetics and ITC studies, binding
      of DHF is accompanied by the net uptake of water. Although different osmolytes
      have similar effects on NADPH binding, variable results are observed when DHF
      binding is probed. Sensitivity to water activity can also be probed by an in vivo
      selection using the antibacterial drug, trimethoprim, where the water content of
      the media is decreased by increasing concentrations of sorbitol. The ability of
      wild type and mutant clones of R67 DHFR to allow host Escherichia coli to grow in
      the presence of trimethoprim plus added sorbitol parallels the catalytic
      efficiency of the DHFR clones, indicating water content strongly correlates with
      the in vivo function of R67 DHFR.

PMID- 18086668
TI  - Cytochrome b5 inhibits electron transfer from NADPH-cytochrome P450 reductase to
      ferric cytochrome P450 2B4.
AB  - Experiments demonstrating that cytochrome (cyt) b5 inhibits the activity of
      cytochrome P450 2B4 (cyt P450 2B4) at higher concentrations suggested that cyt b5
      was occupying the cyt P450 reductase-binding site on cyt P450 2B4 and preventing
      the reduction of ferric cyt P450 (Zhang, H., Im, S.-C., and Waskell, L. (2007) J.
      Biol. Chem. 282, 29766-29776). In this work experiments were undertaken with
      manganese-containing cyt b5 (Mn-cyt b5) to test this hypothesis. Because Mn-cyt
      b5 does not undergo oxidation state changes under our experimental conditions,
      interpretation of the experimental results was unambiguous. The rate of electron
      transfer from cyt P450 reductase to ferric cyt P450 2B4 was decreased by Mn-cyt
      b5 in a concentration-dependent manner. Moreover, reduction of cyt P450 2B4 by
      cyt P450 reductase was incomplete in the presence of Mn-cyt b5. At a Mn-cyt
      b(5):cyt P450 2B4:cyt P450 reductase molar ratio of 5:1:1, the rate of reduction
      of ferric cyt P450 was decreased by 10-fold, and only 30% of the cyt P450 was
      reduced, whereas 70% remained oxidized. It could be demonstrated that Mn-cyt b5
      had its effect by acting on cyt P450, not the reductase, because the reduction of
      cyt c by cyt P450 reductase in the presence of Mn-cyt b5 was not effected.
      Furthermore, under steady-state conditions in the cyt P450 reconstituted system,
      Mn-cyt b5, which lacks the ability to reduce oxyferrous cyt P450 2B4, was unable
      to stimulate the activity of cyt P450. Mn-cyt b5 only inhibited the cyt P450 2B4
      activity. In conjunction with site-directed mutagenesis studies and experiments
      that strongly suggested that cyt b5 competed with cyt P450 reductase for binding
      to cyt P450, the current investigation demonstrates unequivocally that cyt b5
      inhibits the activity of cyt P450 2B4 by preventing cyt P450 reductase from
      binding to cyt P450, a prerequisite for electron transfer from cyt P450 reductase
      to cyt P450 and catalysis.

PMID- 18086669
TI  - Co-administration of ciliary neurotrophic factor with its soluble receptor
      protects against neuronal death and enhances neurite outgrowth.
AB  - Attempts to promote neuronal survival and repair with ciliary neurotrophic factor
      (CNTF) have met with limited success. The variability of results obtained with
      CNTF may, in part, reflect the fact that some of the biological actions of the
      cytokine are mediated by a complex formed between CNTF and its specific receptor,
      CNTFRalpha, which exists in both membrane-bound and soluble forms. In this study,
      we compared the actions of CNTF alone and CNTF complexed with soluble CNTFRalpha
      (hereafter termed "Complex") on neuronal survival and growth. Although CNTF alone
      produced limited effects, Complex protected against glutamate-mediated
      excitotoxicity via gap junction-dependent and -independent mechanisms. Further
      examination revealed that only Complex promoted neurite outgrowth. Differential
      gene expression analysis revealed that, compared with CNTF alone, Complex
      differentially regulates several neuroprotective and neurotrophic genes.
      Collectively, these findings indicate that CNTF exerts more robust effects on
      neuronal survival and growth when applied in combination with its soluble
      receptor.

PMID- 18086670
TI  - Shear- and compression-induced chondrocyte transcription requires MAPK activation
      in cartilage explants.
AB  - Chondrocytes regulate the composition of cartilage extracellular matrix in
      response to mechanical signals, but the intracellular pathways involved in
      mechanotransduction are still being defined. Mitogen-activated protein kinase
      (MAPK) pathways are activated by static and dynamic compression of cartilage,
      which simultaneously induce intratissue fluid flow, pressure gradients, cell, and
      matrix deformation. First, to determine whether cell and matrix deformation alone
      could induce MAPK activation, we applied dynamic shear to bovine cartilage
      explants. Using Western blotting, we measured ERK1/2 and p38 activation at
      multiple time points over 24 h. Distinct activation time courses were observed
      for different MAPKs: a sustained 50% increase for ERK1/2 and a delayed increase
      in p38 of 180%. We then investigated the role of MAPK activation in mechano
      induced chondrocyte gene expression. Cartilage explants were preincubated with
      inhibitors of ERK1/2 and p38 activation before application of 1-24 h of three
      distinct mechanical stimuli relevant to in vivo loading (50% static compression,
      3% dynamic compression at 0.1 Hz, or 3% dynamic shear at 0.1 Hz). mRNA levels of
      selected genes involved in matrix homeostasis were measured using real-time PCR
      and analyzed by k-means clustering to characterize the time- and load-dependent
      effects of the inhibitors. Most genes examined required ERK1/2 and p38 activation
      to be regulated by these loading regimens, including matrix proteins aggrecan and
      type II collagen, matrix metalloproteinases MMP13, and ADAMTS5, and transcription
      factors downstream of the MAPK pathway, c-Fos, and c-Jun. Thus, we demonstrated
      that the MAPK pathway is a central conduit for transducing mechanical forces into
      biological responses in cartilage.

PMID- 18086671
TI  - The PHB1/2 phosphocomplex is required for mitochondrial homeostasis and survival
      of human T cells.
AB  - Many immune pathologies are the result of aberrant regulation of T lymphocytes. A
      functional proteomics approach utilizing two-dimensional gel electrophoresis
      coupled with mass spectrometry was employed to identify differentially expressed
      proteins in response to T cell activation. Two members of the prohibitin family
      of proteins, Phb1 and Phb2, were determined to be up-regulated 4-5-fold upon
      activation of primary human T cells. Furthermore, their expression was dependent
      upon CD3 and CD28 signaling pathways that synergistically led to the up
      regulation (13-15-fold) of Phb1 and Phb2 mRNA levels as early as 48 h after
      activation. Additionally, orthophosphate labeling coupled with phosphoamino acid
      analysis identified Phb1 to be serine and Phb2 serine and tyrosine
      phosphorylated. Tyrosine phosphorylation of Phb2 was mapped to Tyr248 using mass
      spectrometry and confirmed by mutagenesis and phosphospecific antibodies. In
      contrast to previous reports of Phb1 and Phb2 being nuclear localized,
      subcellular fractionation, immunofluorescent, and electron microscopy revealed
      both proteins to localize to the mitochondrial inner membrane of human T cells.
      Accordingly, small interfering RNA-mediated knockdown of Phbs in Kit225 cells
      resulted in disruption of mitochondrial membrane potential. Additionally, Phb1
      and Phb2 protein levels were up-regulated 2.5-fold during cytokine deprivation
      mediated apoptosis of Kit225 cells, suggesting this complex plays a protective
      role in human T cells. Taken together, Phb1 and Phb2 are novel phosphoproteins up
      regulated during T cell activation that function to maintain mitochondrial
      integrity and thus represent previously unrecognized therapeutic targets for
      regulating T cell activation, differentiation, viability, and function.

PMID- 18086672
TI  - Interleukin-18 suppresses adiponectin expression in 3T3-L1 adipocytes via a novel
      signal transduction pathway involving ERK1/2-dependent NFATc4 phosphorylation.
AB  - An inverse correlation between the pro-inflammatory cytokine interleukin-18 and
      the anti-atherogenic adipokine adiponectin has been reported in the chronic
      pathological conditions obesity, insulin resistance, coronary artery disease, and
      metabolic syndrome. We investigated whether this relationship is coincidental or
      has a causal basis. Here we show that interleukin-18 (IL-18) suppresses
      adiponectin transcription, mRNA expression, and secretion by 3T3-L1 adipocytes.
      IL-18 suppresses adiponectin promoter-reporter activity, an effect reversed by
      deletion or mutation of the NFATc4 core DNA-binding site. IL-18 induces NFATc4
      phosphorylation (Ser(676)), nuclear translocation, and in vivo DNA binding. IL-18
      induces ERK1/2 phosphorylation and enzyme activity, and pretreatment with the MEK
      inhibitor U0126, ERK1/2 inhibitor PD98059, or small interference RNA targeted to
      ERK1/2 attenuates ERK1/2 activation and NFATc4 phosphorylation. Finally,
      inhibition of ERK1/2 or NFATc4 knockdown reverses IL-18-mediated adiponectin
      suppression. In contrast to its inhibitory effects on adiponectin expression, IL
      18 potently stimulates PAI-1 secretion. These data demonstrate for the first time
      that IL-18 selectively suppresses adiponectin expression via ERK1/2-dependent
      NFATc4 activation and suggest that the inverse relationship observed between IL
      18 and adiponectin in various chronic pathological conditions is causally
      related. Thus, targeting IL-18 expression may enhance adiponectin expression and
      mitigate disease progression.

PMID- 18086673
TI  - beta-arrestin-biased agonism at the beta2-adrenergic receptor.
AB  - Classically, the beta 2-adrenergic receptor (beta 2AR) and other members of the
      seven-transmembrane receptor (7TMR) superfamily activate G protein-dependent
      signaling pathways in response to ligand stimulus. It has recently been
      discovered, however, that a number of 7TMRs, including beta 2AR, can signal via
      beta-arrestin-dependent pathways independent of G protein activation. It is
      currently unclear if among beta 2AR agonists there exist ligands that
      disproportionately signal via G proteins or beta-arrestins and are hence
      "biased." Using a variety of approaches that include highly sensitive
      fluorescence resonance energy transfer-based methodologies, including a novel
      assay for receptor internalization, we show that the majority of known beta 2AR
      agonists exhibit relative efficacies for beta-arrestin-associated activities
      (beta-arrestin membrane translocation and beta 2AR internalization) identical to
      the irrelative efficacies for G protein-dependent signaling (cyclic AMP
      generation). However, for three betaAR ligands there is a marked bias toward beta
      arrestin signaling; these ligands stimulate beta-arrestin-dependent receptor
      activities to a much greater extent than would be expected given their efficacy
      for G protein-dependent activity. Structural comparison of these biased ligands
      reveals that all three are catecholamines containing an ethyl substitution on the
      alpha-carbon, a motif absent on all of the other, unbiased ligands tested. Thus,
      these studies demonstrate the potential for developing a novel class of 7TMR
      ligands with a distinct bias for beta-arrestin-mediated signaling.

PMID- 18086674
TI  - Autoantibody-catalyzed hydrolysis of amyloid beta peptide.
AB  - We describe IgM class human autoantibodies that hydrolyze amyloid beta peptide 1
      40 (Abeta40). A monoclonal IgM from a patient with Waldenstrom's
      macroglobulinemia hydrolyzed Abeta40 at the Lys-28-Gly-29 bond and Lys-16-Ala-17
      bonds. The catalytic activity was inhibited stoichiometrically by an
      electrophilic serine protease inhibitor. Treatment with the catalytic IgM blocked
      the aggregation and toxicity of Abeta40 in neuronal cell cultures. IgMs purified
      from the sera of patients with Alzheimer disease (AD) hydrolyzed Abeta40 at rates
      superior to IgMs from age-matched humans without dementia. IgMs from non-elderly
      humans expressed the least catalytic activity. The reaction rate was sufficient
      to afford appreciable degradation at physiological Abeta and IgM concentrations
      found in peripheral circulation. Increased Abeta concentrations in the AD brain
      are thought to induce neurodegenerative effects. Peripheral administration of
      Abeta binding antibodies has been suggested as a potential treatment of AD. Our
      results suggest that catalytic IgM autoantibodies can help clear Abeta, and they
      open the possibility of using catalytic Abs for AD immunotherapy.

PMID- 18086675
TI  - Mitochondrial uncoupling protein-2 mediates steatotic liver injury following
      ischemia/reperfusion.
AB  - Steatotic livers are not used for transplantation because they have a reduced
      tolerance for ischemic events with reduced ATP levels and greater levels of
      cellular necrosis, which ultimately result in total organ failure. Mitochondrial
      uncoupling protein-2 (UCP2) is highly expressed in steatotic livers and may be
      responsible for liver sensitivity to ischemia through mitochondrial and ATP
      regulation. To test this hypothesis, experiments were conducted in lean and
      steatotic (ob/ob), wild-type, and UCP2 knock-out mice subjected to total warm
      hepatic ischemi-a/reperfusion. Although ob/ob UCP2 knock-out mice and ob/ob mice
      have a similar initial phenotype, ob/ob UCP2 knock-out animal survival was 83%
      when compared with 30% in ob/ob mice 24 h after reperfusion. Serum alanine
      aminotransferase concentrations and hepatocellular necrosis were decreased in the
      ob/ob UCP2 knock-out mice when compared with ob/ob mice subjected to ischemia.
      Liver ATP levels were increased in the ob/ob UCP2 knock-out animals after
      reperfusion when compared with the ob/ob mice but remained below the
      concentrations from lean livers. Lipid peroxidation (thiobarbituric acid-reactive
      substances) increased after reperfusion most significantly in the steatotic
      groups, but the increase was not affected by UCP2 deficiency. These results
      reveal that UCP2 expression is a critical factor, which sensitizes steatotic
      livers to ischemic injury, regulating liver ATP levels after ischemia and
      reperfusion.

PMID- 18086676
TI  - Amino acids allosterically regulate the thiamine diphosphate-dependent alpha-keto
      acid decarboxylase from Mycobacterium tuberculosis.
AB  - The gene rv0853c from Mycobacterium tuberculosis strain H37Rv codes for a
      thiamine diphosphate-dependent alpha-keto acid decarboxylase (MtKDC), an enzyme
      involved in the amino acid degradation via the Ehrlich pathway. Steady state
      kinetic experiments were performed to determine the substrate specificity of
      MtKDC. The mycobacterial enzyme was found to convert a broad spectrum of branched
      chain and aromatic alpha-keto acids. Stopped-flow kinetics showed that MtKDC is
      allosterically activated by alpha-keto acids. Even more, we demonstrate that also
      amino acids are potent activators of this thiamine diphosphate-dependent enzyme.
      Thus, metabolic flow through the Ehrlich pathway can be directly regulated at the
      decarboxylation step. The influence of amino acids on MtKDC catalysis was
      investigated, and implications for other thiamine diphosphate-dependent enzymes
      are discussed.

PMID- 18086677
TI  - Dynamic regulation of neutrophil survival through tyrosine phosphorylation or
      dephosphorylation of caspase-8.
AB  - Efficient expression of innate immunity is critically dependent upon the capacity
      of the neutrophil to be activated rapidly in the face of an acute threat and to
      involute once that threat has been eliminated. Here we report a novel mechanism
      regulating neutrophil survival dynamically through the tyrosine phosphorylation
      or dephosphorylation of caspase-8. Caspase-8 is tyrosine-phosphorylated in
      freshly isolated neutrophils but spontaneously dephosphorylates in culture, in
      association with the progression of constitutive apoptosis. Phosphorylation of
      caspase-8 on Tyr-310 facilitates its interaction with the Src-homology domain 2
      containing tyrosine phosphatase-1 (SHP-1) and enables SHP-1 to dephosphorylate
      caspase-8, permitting apoptosis to proceed. The non-receptor tyrosine kinase,
      Lyn, can phosphorylate caspase-8 on Tyr-397 and Tyr-465, rendering it resistant
      to activational cleavage and inhibiting apoptosis. Exposure to lipopolysaccharide
      reduces SHP-1 activity and binding to caspase-8, caspase-8 activity, and rates of
      spontaneous apoptosis. SHP-1 activity is reduced and Lyn increased in neutrophils
      from patients with sepsis, in association with profoundly delayed apoptosis;
      inhibition of Lyn can partially reverse this delay. Thus the phosphorylation and
      dephosphorylation of caspase-8, mediated by Lyn and SHP-1, respectively,
      represents a novel, dynamic post-translational mechanism for the regulation of
      neutrophil apoptosis whose dysregulation contributes to persistent neutrophil
      survival in sepsis.

PMID- 18086678
TI  - Dynamics of intracellular oxygen in PC12 Cells upon stimulation of
      neurotransmission.
AB  - Neurotransmission, synaptic plasticity, and maintenance of membrane excitability
      require high mitochondrial activity in neurosecretory cells. Using a fluorescence
      based intracellular O2 sensing technique, we investigated the respiration of
      differentiated PC12 cells upon depolarization with 100 mm K+. Single cell
      confocal analysis identified a significant depolarization of the plasma membrane
      potential and a relatively minor depolarization of the mitochondrial membrane
      potential following K+ exposure. We observed a two-phase respiratory response: a
      first intense spike lasting approximately 10 min, during which average
      intracellular O2 was reduced from 85-90% of air saturation to 55-65%, followed by
      a second wave of smaller amplitude and longer duration. The fast rise in O2
      consumption coincided with a transient increase in cellular ATP by approximately
      60%, which was provided largely by oxidative phosphorylation and by glycolysis.
      The increase of respiration was orchestrated mainly by Ca2+ release from the
      endoplasmic reticulum, whereas the influx of extracellular Ca2+ contributed
      approximately 20%. Depletion of Ca2+ stores by ryanodine, thapsigargin, and 4
      chloro-m-cresol reduced the amplitude of respiratory spike by 45, 63, and 71%,
      respectively, whereas chelation of intracellular Ca2+ abolished the response.
      Uncoupling of the mitochondria with the protonophore carbonyl cyanide p
      trifluoromethoxyphenylhydrazone amplified the responses to K+; elevated
      respiration induced a profound deoxygenation without increasing the cellular ATP
      levels reduced by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. Cleavage of
      synaptobrevin 2 by tetanus toxin, known to reduce neurotransmission, did not
      affect the respiratory response to K+, whereas the general excitability of d PC12
      cells increased.

PMID- 18086679
TI  - A bipartite trigger for dislocation directs the proteasomal degradation of an
      endoplasmic reticulum membrane glycoprotein.
AB  - Polypeptides are organized into distinct substructures, termed protein domains,
      that are often associated with diverse functions. These modular units can act as
      binding sites, areas of post-translational modification, and sites of complex
      multimerization. The human cytomegalovirus US2 gene product is organized into
      discrete domains that together catalyze the proteasome-dependent degradation of
      class I major histocompatibility complex heavy chains. US2 co-opts the endogenous
      ER quality control pathway in order to dispose of class I. The US2 endoplasmic
      reticulum (ER)-lumenal region is the class I binding domain, whereas the carboxyl
      terminus can be referred to as the degradation domain. In the present study, we
      examined the role of the US2 transmembrane domain in virus-mediated class I
      degradation. Replacement of the US2 transmembrane domain with that of the CD4
      glycoprotein completely blocked the ability of US2 to induce class I destruction.
      A more precise mutagenesis revealed that subregions of the US2 transmembrane
      domain differ in their ability to trigger class I degradation. Collectively, the
      data support a model in which US2-mediated class I degradation occurs as a highly
      regulated process where the US2 transmembrane domain and cytoplasmic tail work in
      concert to eliminate class I molecules. Host factors, including a signal
      peptidase complex, probably associate with the US2 molecule in a coordinated
      fashion to create a predislocation complex to promote the extraction of class I
      out of the ER. The results imply that the ER quality control machinery may
      recognize and eliminate misfolded proteins using a similar multistep regulated
      process.

PMID- 18086680
TI  - Aromatic residues in the C-terminal domain 2 are required for Nanog to mediate
      LIF-independent self-renewal of mouse embryonic stem cells.
AB  - Nanog was identified by its ability to sustain the LIF-independent self-renewal
      of mouse embryonic stem (ES) cells and has recently been shown to play a role in
      reprogramming adult fibroblasts into pluripotent stem cells. However, little is
      known about the structural basis of these remarkable activities of Nanog. We have
      previously identified an unusually strong transactivator named CD2 at its C
      terminus. Here we demonstrate that CD2 is required for Nanog to mediate ES cell
      self-renewal. Furthermore, deletion and point mutation analysis revealed that CD2
      relies on at least seven aromatic amino acid residues to generate its potent
      transactivating activity. A mutant Nanog bearing alanine substitutions for these
      seven residues fails to confer LIF-independent self-renewal in mouse ES cells.
      Substitution of CD2 by the viral transactivator VP16 gave rise to Nanog-VP16,
      which is 10 times more active than wild-type Nanog in ES cells. Surprisingly, the
      expression of Nanog-VP16 in mouse ES cells induces differentiation and is thus
      unable to sustain LIF-independent self-renewal for mouse ES cells. Taken
      together, our results demonstrate that the CD2 domain of Nanog is a unique
      transactivator that utilizes aromatic residues to confer specific activity
      absolutely required for ES self-renewal.

PMID- 18086681
TI  - Selective intracellular release of copper and zinc ions from
      bis(thiosemicarbazonato) complexes reduces levels of Alzheimer disease amyloid
      beta peptide.
AB  - Copper and zinc play important roles in Alzheimer disease pathology with recent
      reports describing potential therapeutics based on modulation of metal
      bioavailability. We examined the ability of a range of metal
      bis(thiosemicarbazonato) complexes (MII(btsc), where M=CuII or ZnII) to increase
      intracellular metal levels in Chinese hamster ovary cells overexpressing amyloid
      precursor protein (APP-CHO) and the subsequent effect on extracellular levels of
      amyloid-beta peptide (Abeta). The CuII(btsc) complexes were engineered to be
      either stable to both a change in oxidation state and dissociation of metal or
      susceptible to intracellular reduction and dissociation of metal. Treatment of
      APP-CHO cells with stable complexes resulted in elevated levels of intracellular
      copper with no effect on the detected levels of Abeta. Treatment with complexes
      susceptible to intracellular reduction increased intracellular copper levels but
      also resulted in a dose-dependent reduction in the levels of monomeric Abeta.
      Treatment with less stable ZnII(btsc) complexes increased intracellular zinc
      levels with a subsequent dose-dependent depletion of monomeric Abeta levels. The
      increased levels of intracellular bioavailable copper and zinc initiated a
      signaling cascade involving activation of phosphoinositol 3-kinase and c-Jun N
      terminal kinase. Inhibition of these enzymes prevented Abeta depletion induced by
      the MII(btsc) complexes. Inhibition of metalloproteases also partially restored
      Abeta levels, implicating metal-driven metalloprotease activation in the
      extracellular monomeric Abeta depletion. However, a role for alternative metal
      induced Abeta metabolism has not been ruled out. These studies demonstrate that
      MII(btsc) complexes have potential for Alzheimer disease therapy.

PMID- 18086682
TI  - Hsp60 regulation of tumor cell apoptosis.
AB  - Molecular chaperones may promote cell survival, but how this process is
      regulated, especially in cancer, is not well understood. Using high throughput
      proteomics screening, we identified the cell cycle regulator and apoptosis
      inhibitor survivin as a novel protein associated with the molecular chaperone
      Hsp60. Acute ablation of Hsp60 by small interfering RNA destabilizes the
      mitochondrial pool of survivin, induces mitochondrial dysfunction, and activates
      caspase-dependent apoptosis. This response involves disruption of an Hsp60-p53
      complex, which results in p53 stabilization, increased expression of pro
      apoptotic Bax, and Bax-dependent apoptosis. In vivo, Hsp60 is abundantly
      expressed in primary human tumors, as compared with matched normal tissues, and
      small interfering RNA ablation of Hsp60 in normal cells is well tolerated and
      does not cause apoptosis. Therefore, Hsp60 orchestrates a broad cell survival
      program centered on stabilization of mitochondrial survivin and restraining of
      p53 function, and this process is selectively exploited in cancer. Hsp60
      inhibitors may function as attractive anticancer agents by differentially
      inducing apoptosis in tumor cells.

PMID- 18086683
TI  - Defective ENaC processing and function in tissue kallikrein-deficient mice.
AB  - An inverse relationship exists between urinary tissue kallikrein (TK) excretion
      and blood pressure in humans and rodents. In the kidney TK is synthesized in
      large amounts in the connecting tubule and is mainly released into the urinary
      fluid where its function remains unknown. In the present study mice with no
      functional gene coding for TK (TK-/-) were used to test whether the enzyme
      regulates apically expressed sodium transporters. Semiquantitative immunoblotting
      of the renal cortex revealed an absence of the 70-kDa form of gamma-ENaC in TK-/-
      mice. Urinary Na+ excretion after amiloride injection was blunted in TK-/- mice,
      consistent with reduced renal ENaC activity. Amiloride-sensitive transepithelial
      potential difference in the colon, where TK is also expressed, was decreased in
      TK-/- mice, whereas amiloride-sensitive alveolar fluid clearance in the lung,
      where TK is not expressed, was unchanged. In mice lacking the B2 receptor for
      kinins, the abundance of the 70-kDa form of gamma-ENaC was increased, indicating
      that its absence in TK-/- mice is not kinin-mediated. Incubation of membrane
      proteins from renal cortex of TK-/- mice with TK resulted in the appearance of
      the 70-kDa band of the gamma-ENaC, indicating that TK was able to promote gamma
      ENaC cleavage in vitro. Finally, in mouse cortical collecting ducts isolated and
      microperfused in vitro, the addition of TK in the luminal fluid increased
      significantly intracellular Na+ concentration, consistent with an activation of
      the luminal entry of the cation. The results demonstrate that TK, like several
      other proteases, can activate ENaC in the kidney and the colon.

PMID- 18086684
TI  - A Temperature-sensitive mutation in the Arabidopsis thaliana phosphomannomutase
      gene disrupts protein glycosylation and triggers cell death.
AB  - Eukaryotic phosphomannomutases (PMMs) catalyze the interconversion of mannose 6
      phosphate to mannose 1-phosphate and are essential to the biosynthesis of GDP
      mannose. As such, plant PMMs are involved in ascorbic acid (AsA) biosynthesis and
      N-glycosylation. We report on the conditional phenotype of the temperature
      sensitive Arabidopsis thaliana pmm-12 mutant. Mutant seedlings were
      phenotypically similar to wild type seedlings when grown at 16-18 degrees C but
      died within several days after transfer to 28 degrees C. This phenotype was
      observed throughout both vegetative and reproductive development. Protein
      extracts derived from pmm-12 plants had lower PMM protein and enzyme activity
      levels. In vitro biochemical analysis of recombinant proteins showed that the
      mutant PMM protein was compromised in its catalytic efficiency (K cat/K m).
      Despite significantly decreased AsA levels in pmm-12 plants, AsA deficiency could
      not account for the observed phenotype. Since, at restrictive temperature, total
      glycoprotein patterns were altered and glycosylation of protein-disulfide
      isomerase was perturbed, we propose that a deficiency in protein glycosylation is
      responsible for the observed cell death phenotype.

PMID- 18086685
TI  - A new algorithm for cluster analysis of genomic methylation: the Helicobacter
      pylori case.
AB  - MOTIVATION: The genomic methylation analysis is useful to type bacteria that have
      a high number of expressed type II methyltransferases. Methyltransferases are
      usually committed to Restriction and Modification (R-M) systems, in which the
      restriction endonuclease imposes high pressure on the expression of the cognate
      methyltransferase that hinder R-M system loss. Conventional cluster methods do
      not reflect this tendency. An algorithm was developed for dendrogram construction
      reflecting the propensity for conservation of R-M Type II systems. RESULTS: The
      new algorithm was applied to 52 Helicobacter pylori strains from different
      geographical regions and compared with conventional clustering methods. The
      algorithm works by first grouping strains that share a common minimum set of R-M
      systems and gradually adds strains according to the number of the R-M systems
      acquired. Dendrograms revealed a cluster of African strains, which suggest that R
      M systems are present in H.pylori genome since its human host migrates from
      Africa. AVAILABILITY: The software files are available at
      http://www.ff.ul.pt/paginas/jvitor/Bioinformatics/MCRM_algorithm.zip.

PMID- 18086686
TI  - affyGG: computational protocols for genetical genomics with Affymetrix arrays.
AB  - MOTIVATION: Affymetrix arrays use multiple probes per gene to measure mRNA
      abundances. Standard software takes averages over probes. Important information
      may be lost if polymorphisms in the mRNA affect the hybridization of individual
      probes. RESULTS: We present custom software to analyze genetical genomics
      experiments in human, mouse and other organisms: (i) an R package providing
      functions for QTL analysis at the individual probe level and (ii) Perl scripts
      providing custom tracks in the UCSC Genome Browser to check for sequence
      polymorphisms in probe regions. AVAILABILITY:
      http://gbic.biol.rug.nl/supplementary.

PMID- 18086687
TI  - People and money matter: investment lessons from the Ontario Heart Health
      Program, Canada.
AB  - Resource allocation is a critical issue for public health decision-makers. Yet
      little is known about the level and type of resources needed to build capacity to
      plan and implement comprehensive programs. This paper examines the relationships
      between investments and changes in organizational capacity and program
      implementation in the first phase (1998-2003) of the Ontario Heart Health Program
      (OHHP)--a province-wide, comprehensive public health program that involved 40
      community partnerships. The study represents a subset of findings from a
      provincial evaluation. Investments, organizational capacity of public health
      units and implementation of heart health activities were measured longitudinally.
      Investment information was gathered annually from the provincial government,
      local public health units and community partners using standard reports, and was
      available from 1998 to 2002. Organizational capacity and program implementation
      were measured using a written survey, completed by all health units at five
      measurement times from 1994 to 2002. Combining provincial and local sources, the
      average total investment by year five was $1.66 per capita. Organizational
      capacity of public health units and implementation of heart health activities
      increased both before and during the first 2 years of the OHHP, and then
      plateaued at a modest level for capacity and a low level for implementation after
      that. Amount of funding was positively associated with organizational capacity,
      yet this association was overpowered by the negative influence of turnover of a
      key staff position. Regression analysis indicated that staff turnover explained
      23% of local variability in organizational capacity. Findings reinforce the need
      for adequate investment and retention of key staff positions in complex
      partnership programs. Better accounting of public health investments, including
      monetary and in-kind investments, is needed to inform decisions about the amount
      and duration of public health investments that will lead to effective program
      implementation.

PMID- 18086688
TI  - School children as health change agents in Magu, Tanzania: a feasibility study.
AB  - The feasibility of an action-oriented and participatory educational approach,
      where school children function as health change agents, in a rural community of
      (Magu district) Tanzania was explored. Observations, in-depth interviews and
      focus group discussions with pupils, teachers and parents were undertaken.
      Findings showed that study participants favoured an approach where school
      children played an active role as health change agents in a combined school and
      community health education project. This conclusion contradicts traditional views
      in many African cultures where power, status and wisdom are usually closely
      associated with old age. However, a number of barriers were found, including the
      curriculum, time constraints, class size, teaching materials and teachers' skills
      and working conditions. The idea that pupils act as health change agents in the
      community as part of an action-oriented and participatory health education
      approach in schools was supported. A list of factors to consider when planning an
      action-oriented health education project is provided and discussed.

PMID- 18086689
TI  - Nuclear Regulatory Authority low energy germanium detection system: performance
      for the uranium individual monitoring.
AB  - The lung counter facility of the Nuclear Regulatory Authority (ARN) is presented.
      A calibration was carried out using the Lawrence Livermore National Laboratory
      (LLNL) phantom. This phantom is provided with a pair of lungs and lymph nodes
      containing uranium homogeneously distributed and a set of four overlay plates
      covering a chest wall thickness (CWT) ranging from 1.638 to 3.871 cm. Individual
      organ calibration factors were acquired for 235U photopeaks energies and for each
      effective chest thickness. Using these factors, a collection of theoretical
      fitting curves were found. A counting efficiency formulae and a curve for
      simultaneously active lymph nodes and lung was obtained and checked through
      measures. Background measurements of the chamber with and without volunteer
      persons were performed in order to obtain the detection limits (DL) of the
      system. As this task involves the knowledge of the volunteers CWTs, these
      magnitudes were determined through formulae selected from the literature taking
      into account the detection system characteristics. The deviation in the CWT
      assigned to an individual, generated by applying different equations, produces
      variations up to 33% in the estimations of the incorporated activity and DL. An
      analysis of the changes in efficiencies as consequences of the detectors
      locations and CWT was also performed. This reveals that the DL of the camera
      (detectors, shield and blank phantom) is between 2.7 and 6.4 Bq of 235U, which
      implies 4.9 and 11.5 mg lung burden of natural uranium. An estimation of the
      minimum detectable intake performed with the DL considering blank persons shows
      that a system with the characteristics described is only adequate for non-routine
      individual monitoring.

PMID- 18086690
TI  - Validating a MCNPX model of Mg(Ar) and TE(TE) ionisation chambers exposed to 60CO
      gamma rays.
AB  - For an accurate determination of the absorbed doses in complex radiation fields
      (e.g. mixed neutron-gamma fields), a better interpretation of the response of
      ionisation chambers is required. This study investigates a model of the
      ionisation chambers using a different approach, analysing the collected charge
      per minute as a response of the detector instead of the dose. The MCNPX Monte
      Carlo code is used. In this paper, the model is validated using a well-known
      irradiation field only: a (60)Co source. The detailed MCNPX models of a Mg(Ar)
      and TE(TE) ionisation chamber is investigated comparing the measured charge per
      minute obtained free-in-air and in a water phantom with the simulated results.
      The difference between the calculations and the measurements for the TE(TE)
      chamber is within +/-2% whereas for the Mg(Ar) chamber is around +7%. The
      systematic discrepancy in the case of Mg(Ar) chamber is expected to be caused by
      an overestimation of the sensitive volume.

PMID- 18086691
TI  - Surgical treatment of postinfarction anterior left ventricular aneurysms: linear
      vs. patch plasty repair.
AB  - BACKGROUND: The patch plasty repair is increasingly advocated over linear closure
      in the surgical treatment of postinfarction anterior left ventricular aneurysm
      (LVA). A comparative estimate of the clinical results of these two techniques
      seemed in order. METHODS: Between 1985 and 2004, 53 patients (mean age of 64.2+/
      8.3 years) underwent repair of anterior LVA. Twenty-seven patients underwent
      linear repair (group 1) and 26 patients patch plasty (group 2). The mean left
      ventricular ejection fraction was 33.9+/-8.2% in group 1 vs. 29.7+/-10.2% in
      group 2 (P=0.118). Preoperatively 85.2% of patients in group 1 were in NYHA
      functional class III or IV vs. 88.5% in group 2 (P=0.71). All patients had
      preoperative recurrent ventricular tachycardia (VT) and non-guided encircling
      cryoablation for treatment of VT was performed in all patients. Coronary
      revascularization was performed in 29.6% of patients in group 1 and 42.3% in
      group 2 (P=0.398). RESULTS: The overall in-hospital mortality was 1.9% as one
      patient died of low cardiac output (LCO). LCO was the most frequent early
      postoperative complication and was observed in 66.7% of patients in group 1 vs.
      65.4% in group 2 (P=1.000). LCO was related to right coronary artery disease on
      multivariate analysis (odds ratio 6.9, P=0.0097). Mean follow-up was 6.4+/-4.8
      years (range 1 day-17.5 years). Overall survival at 10 years was 65.5% of
      patients in group 1 vs. 60.6% in group 2 (P=0.395). At 10 years, 91.5% of
      patients were free from VT or sudden death in group 1 vs. 81% in group 2
      (P=0.269). At follow-up the patients' functional status improved and among
      survivors 76.9% in group 1 were in NYHA functional class I-II vs. 62.5% in group
      2 (P=0.432). Deaths from congestive heart failure (CHF) occurred in 38.5% of
      patients in group 1 vs. 55.6% in group 2 (P=0.632). On multivariate analysis a
      preoperative left ventricular end-diastolic pressure above 20 mmHg was a
      predictor of mortality from CHF (odds ratio 9.6, P=0.038). CONCLUSIONS: Our study
      did not reveal significant differences between linear closure and patch plasty
      repair in the short- and long-term. The choice of repair technique should be
      adapted to each patient's anatomical and physiological characteristics.

PMID- 18086692
TI  - Early and mid-term results of off-pump coronary artery bypass grafting in
      patients with end stage renal disease: surgical outcomes after achievement of
      complete revascularization.
AB  - End stage renal disease is a risk factor for mortality after coronary artery
      bypass grafting. We conducted a retrospective review of 37 consecutive dialysis
      dependent patients who underwent off-pump coronary artery bypass grafting between
      April 2001 and July 2004. Complete revascularization was successfully performed
      in all patients. The mean number of anastomoses was 3.7, and early graft patency
      was 98.8%. Thirty-day mortality was 2.7%. In-hospital mortality was 8.1%. At a
      mean follow-up of 26 months, there were six late deaths including one cardiac
      death, and five cardiac events. Actuarial survival rate at one and three years
      was 88.8% and 77.0%, respectively. Cardiac event free rate at one and three years
      was 85.9% and 72.6%, respectively. Multivariate analysis revealed that
      preoperative left ventricular ejection fraction (P=0.003) and smoking history
      (P=0.026) were significant predictors for mid-term mortality, and co-existing
      peripheral vascular disease was a significant predictor for cardiac events
      (P=0.033). Early and mid-term outcomes after off-pump coronary artery bypass
      grafting in patients with end stage renal disease have acceptable mortality rate
      with excellent early graft patency, while low ejection fraction and smoking
      history were significant risk factors for mid-term survival, and co-existing
      peripheral vascular disease was a significant predictor for cardiac events.

PMID- 18086693
TI  - Unexpected antimicrobial effect of statins.
AB  - OBJECTIVES: Epidemiological studies of statins have suggested a link between
      statin therapy and a decreased risk of sepsis. It has been proposed that the
      mechanism underlying this apparent protective effect of statins relates to their
      known immunomodulatory and anti-inflammatory effects. The aim of this study was
      to explore the antimicrobial effect of statins. METHODS: Simvastatin (Merck) and
      fluvastatin (Novartis) were both tested against six of each of methicillin
      susceptible and -resistant Staphylococcus aureus (MSSA + MRSA), and vancomycin
      sensitive and -resistant enterococci (VSE + VRE) using a microtitre dilution
      method. The test was repeated five times for both statins against all 24
      isolates. Vancomycin, linezolid and propranolol were used as controls, as
      appropriate. RESULTS AND DISCUSSION: Simvastatin showed a significant
      antimicrobial effect against MSSA (mean MIC 29.2 mg/L) and to a lesser extent
      against MRSA (mean MIC 74.9 mg/L). Fluvastatin had a significantly less marked
      antimicrobial effect. Propranolol showed no antimicrobial effect. Simvastatin has
      a considerable antimicrobial effect in vitro and further testing of it is
      warranted.

PMID- 18086694
TI  - First report of qnr genes in Salmonella in The Netherlands.

PMID- 18086695
TI  - The small diverticulum in the right anterior wall of the left atrium.

PMID- 18086696
TI  - Delayed rhythm control of atrial fibrillation may be a cause of failure to
      prevent recurrences: reasons for change to active antiarrhythmic treatment at the
      time of the first detected episode.
AB  - Atrial fibrillation (AF) is associated with impaired functional capacity and
      quality of life and significant morbidity and mortality. The current management
      approach fails to maintain stable sinus rhythm (SR) in the majority of patients.
      For many years, guidelines have recommended antiarrhythmic treatment of a first
      AF episode only if the AF is poorly tolerated, a position that has been
      reinforced by studies showing no mortality or morbidity advantage of rhythm
      control over rate control. During the last decade, research has shown mechanisms
      of self-perpetuation of AF based on electrophysiological and structural
      remodelling induced by AF itself. There is mounting evidence that 'lone' AF is
      because of a host of factors, some of which may be easily treatable, such as
      hypertension, sleep apnoea, and obesity, thus allowing secondary prevention at
      the time of the first episode of AF. According to these concepts, lack of early
      intervention could be one of the reasons for long-term failure of maintenance of
      SR. In this position paper, we propose testing the working hypothesis that if an
      SR maintenance strategy is selected, treatment of AF should commence at the first
      detected episode and should be based on a double strategy of SR restoration and
      aggressive treatment of associated conditions that promote atrial remodelling.

PMID- 18086697
TI  - Job adjustment and absence from work in mid-pregnancy in the Norwegian Mother and
      Child Cohort Study (MoBa).
AB  - BACKGROUND: Pregnant women at work have special needs, and sick leave is common.
      However, job adjustment in pregnancy is addressed in European legislation. Our
      main objective was to examine if job adjustment was associated with reduced
      absence. METHODS: This study is based on the Norwegian Mother and Child Cohort
      Study (MoBa) conducted by the Norwegian Institute of Public Health. 28,611
      employed women filled in questionnaires in weeks 17 and 30 in pregnancy. The risk
      of absence for more than 2 weeks was studied among those who were not absent in
      week 17 (n = 22,932), and the probability of return to work in week 30 among
      those who were absent in week 17 (n = 5679). Data were based on self-report. The
      influence of job adjustment (three categories: not needed, needed but not
      obtained, needed and obtained) was analysed in additive models in multivariable
      binomial regression. Associations with other job characteristics and work
      environment factors were also analysed. RESULTS: The risk of absence for more
      than 2 weeks was 0.308 and the probability of return to work was 0.137. Compared
      with women who needed but did not achieve job adjustment, obtained job adjustment
      was associated with a 0.107 decreased risk of absence (95% confidence interval
      0.090 to 0.125) in a model including other job characteristics and work
      environment factors. Job adjustment was correspondingly associated with a 0.041
      (0.023 to 0.059) increased probability of return to work. Absence was associated
      with adverse work environment, whereas the opposite pattern was found for return
      to work among those who started off being absent. CONCLUSIONS: Job adjustment was
      associated with reduced absence from work in pregnancy. Results should be
      interpreted cautiously because of low participation in MoBa and potential
      information bias from self-reported data.

PMID- 18086698
TI  - Occupational exposure levels to wood dust in Italy, 1996-2006.
AB  - BACKGROUND: Wood dust has been classified as carcinogenic to humans and the
      association with nasal cancer risk has been observed in a large number of
      epidemiological studies. OBJECTIVES: The aim of this study is to summarise data
      about occupational exposure levels to wood dust in Italy and to examine some
      exposure determinants. METHODS: Exposure measurements on wood dust were extracted
      from the SIREP (Italian Information System on Occupational Exposure to
      Carcinogens) database between 1996-2006. Descriptive statistics were calculated
      for exposure-related variables using univariate analyses. The prevalence of
      elevated exposure levels was estimated overall and for some industrial sectors. A
      multifactorial analysis of variance was performed to determine which factors
      influenced exposure levels to wood dust. RESULTS: The total number of exposure
      measurements (n) reported is 10,837, which refer to 10,528 workers and 1181
      companies. The overall arithmetic mean is 1.44 mg/m(3) and the geometric mean is
      0.97 mg/m(3). Industrial sectors at high risk are "manufacture of wood and wood
      products" (n = 5539) as well as "manufacture of furniture" (n = 4347). About 74%
      of exposure measurements report a value <2 mg/m(3). In the multifactorial
      analysis, it has been found that job category, industrial sector, company size
      and geographical location of the company influence the exposure levels.
      CONCLUSIONS: This study confirms the previous findings about occupational
      exposure to wood dust (mainly in wood industry and among woodworking machine
      operators) and suggests further investigations on other risk sectors (building
      and repairing of ships and boats). The potential of the occupational exposure
      database as a source of data for exposure assessment and surveillance is also
      confirmed.

PMID- 18086699
TI  - Red flag on the white reporter: a versatile insulator abuts the white gene in
      Drosophila and is omnipresent in mini-white constructs.
AB  - Much of the research on insulators in Drosophila has been done with transgenic
      constructs using the white gene (mini-white) as reporter. Hereby we report that
      the sequence between the white and CG32795 genes in Drosophila melanogaster
      contains an insulator of a novel kind. Its functional core is within a 368 bp
      segment almost contiguous to the white 3'UTR, hence we name it as Wari (white
      abutting resident insulator). Though Wari contains no binding sites for known
      insulator proteins and does not require Su(Hw) or Mod(mdg4) for its activity, it
      can equally well interact with another copy of Wari and with unrelated Su(Hw)
      dependent insulators, gypsy or 1A2. In its natural downstream position, Wari
      reinforces enhancer blocking by any of the three insulators placed between the
      enhancer and the promoter; again, Wari-Wari, Wari-gypsy or 1A2-Wari pairing
      results in mutual neutralization (insulator bypass) when they precede the
      promoter. The distressing issue is that this element hides in all mini-white
      constructs employed worldwide to study various insulators and other regulatory
      elements as well as long-range genomic interactions, and its versatile effects
      could have seriously influenced the results and conclusions of many works.

PMID- 18086700
TI  - Joint annotation of coding and non-coding single nucleotide polymorphisms and
      mutations in the SNPeffect and PupaSuite databases.
AB  - Single nucleotide polymorphisms (SNPs) are, together with copy number variation,
      the primary source of variation in the human genome. SNPs are associated with
      altered response to drug treatment, susceptibility to disease and other
      phenotypic variation. Furthermore, during genetic screens for disease-associated
      mutations in groups of patients and control individuals, the distinction between
      disease causing mutation and polymorphism is often unclear. Annotation of the
      functional and structural implications of single nucleotide changes thus provides
      valuable information to interpret and guide experiments. The SNPeffect and
      PupaSuite databases are now synchronized to deliver annotations for both non
      coding and coding SNP, as well as annotations for the SwissProt set of human
      disease mutations. In addition, SNPeffect now contains predictions of Tango2: an
      improved aggregation detector, and Waltz: a novel predictor of amyloid-forming
      sequences, as well as improved predictors for regions that are recognized by the
      Hsp70 family of chaperones. The new PupaSuite version incorporates predictions
      for SNPs in silencers and miRNAs including their targets, as well as additional
      methods for predicting SNPs in TFBSs and splice sites. Also predictions for mouse
      and rat genomes have been added. In addition, a PupaSuite web service has been
      developed to enable data access, programmatically. The combined database holds
      annotations for 4,965,073 regulatory as well as 133,505 coding human SNPs and
      14,935 disease mutations, and phenotypic descriptions of 43,797 human proteins
      and is accessible via http://snpeffect.vib.be and
      http://pupasuite.bioinfo.cipf.es/.

PMID- 18086701
TI  - The UCSC Genome Browser Database: 2008 update.
AB  - The University of California, Santa Cruz, Genome Browser Database (GBD) provides
      integrated sequence and annotation data for a large collection of vertebrate and
      model organism genomes. Seventeen new assemblies have been added to the database
      in the past year, for a total coverage of 19 vertebrate and 21 invertebrate
      species as of September 2007. For each assembly, the GBD contains a collection of
      annotation data aligned to the genomic sequence. Highlights of this year's
      additions include a 28-species human-based vertebrate conservation annotation, an
      enhanced UCSC Genes set, and more human variation, MGC, and ENCODE data. The
      database is optimized for fast interactive performance with a set of web-based
      tools that may be used to view, manipulate, filter and download the annotation
      data. New toolset features include the Genome Graphs tool for displaying genome
      wide data sets, session saving and sharing, better custom track management,
      expanded Genome Browser configuration options and a Genome Browser wiki site. The
      downloadable GBD data, the companion Genome Browser toolset and links to
      documentation and related information can be found at: http://genome.ucsc.edu/.

PMID- 18086702
TI  - Creating a ribonuclease T-tat that preferentially recognizes and hydrolyzes HIV-1
      TAR RNA in vitro and in vivo.
AB  - A ribonuclease, RNase T-tat, specifically designed to hydrolyze the TAR RNA of
      HIV-1 virus has been engineered. The protein was made by domain swapping the TAT
      peptide at the loop 3 position of ribonuclease T1. The RNase T-tat maintains a
      guanine-specific RNA hydrolytic activity, and characteristically displayed a
      specific affinity for the TAR RNA of HIV-1. In the in vitro and in vivo assays,
      the RNase T-tat preferentially inhibited the expression of TAR-bearing mRNA
      through cis-TAR targeting, suggesting that RNase T-tat may be potentially useful
      for the disruption of the initial stage of the transcription process of HIV-1
      virus.

PMID- 18086703
TI  - Genome wide screens in yeast to identify potential binding sites and target genes
      of DNA-binding proteins.
AB  - Knowledge of all binding sites for transcriptional activators and repressors is
      essential for computationally aided identification of transcriptional networks.
      The techniques developed for defining the binding sites of transcription factors
      tend to be cumbersome and not adaptable to high throughput. We refined a
      versatile yeast strategy to rapidly and efficiently identify genomic targets of
      DNA-binding proteins. Yeast expressing a transcription factor is mated to yeast
      containing a library of genomic fragments cloned upstream of the reporter gene
      URA3. DNA fragments with target-binding sites are identified by growth of yeast
      clones in media lacking uracil. The experimental approach was validated with the
      tumor suppressor protein p53 and the forkhead protein FoxI1 using genomic
      libraries for zebrafish and mouse generated by shotgun cloning of short genomic
      fragments. Computational analysis of the genomic fragments recapitulated the
      published consensus-binding site for each protein. Identified fragments were
      mapped to identify the genomic context of each binding site. Our yeast screening
      strategy, combined with bioinformatics approaches, will allow both detailed and
      high-throughput characterization of transcription factors, scalable to the
      analysis of all putative DNA-binding proteins.

PMID- 18086704
TI  - Differentiation-dependent lysine 4 acetylation enhances MEF2C binding to DNA in
      skeletal muscle cells.
AB  - Myocyte enhancer factor 2 (MEF2) proteins play a key role in promoting the
      expression of muscle-specific genes in differentiated muscle cells. MEF2 activity
      is regulated by the association with several transcriptional co-factors and by
      post-translational modifications. In the present report, we provide evidence for
      a novel regulatory mechanism of MEF2C activity, which occurs at the onset of
      skeletal muscle differentiation and is based on Lys4 acetylation. This covalent
      modification results in the enhancement of MEF2C binding to DNA and chromatin. In
      particular, we report that the kinetic parameters of MEF2/DNA association change
      substantially upon induction of differentiation to give a more stable complex and
      that this effect is mediated by Lys4 acetylation. We also show that Lys4
      acetylation plays a prominent role in the p300-dependent activation of MEF2C.

PMID- 18086705
TI  - Human Pcf11 enhances degradation of RNA polymerase II-associated nascent RNA and
      transcriptional termination.
AB  - The poly(A) (pA) signal possesses a dual function in 3' end processing of pre
      mRNA and in transcriptional termination of RNA polymerase II (Pol II) for most
      eukaryotic protein-coding genes. A key protein factor in yeast and Drosophila Pol
      II transcriptional termination is the 3'-end processing factor, Pcf11. In vitro
      studies suggest that Pcf11 is capable of promoting the dissociation of Pol II
      elongation complexes from DNA. Moreover, several mutant alleles of yeast Pcf11
      effect termination in vivo. However, functions of human Pcf11 (hPcf11) in Pol II
      termination have not been explored. Here we show that depletion of hPcf11 from
      HeLa cells reduces termination efficiency. Furthermore, we provide evidence that
      hPcf11 is required for the efficient degradation of the 3' product of pA site
      cleavage. Finally, we show that these functions of hPcf11 require an intact pA
      signal.

PMID- 18086706
TI  - What drives the binding of minor groove-directed ligands to DNA hairpins?
AB  - Understanding the molecular basis of ligand-DNA-binding events, and its
      application to the rational design of novel drugs, requires knowledge of the
      structural features and forces that drive the corresponding recognition
      processes. Existing structural evidence on DNA complexation with classical minor
      groove-directed ligands and the corresponding studies of binding energetics have
      suggested that this type of binding can be described as a rigid-body association.
      In contrast, we show here that the binding-coupled conformational changes may be
      crucial for the interpretation of DNA (hairpin) association with a classical
      minor groove binder (netropsin). We found that, although the hairpin form is the
      only accessible state of ligand-free DNA, its association with the ligand may
      lead to its transition into a duplex conformation. It appears that formation of
      the fully ligated duplex from the ligand-free hairpin, occurring via two
      pathways, is enthalpically driven and accompanied by a significant contribution
      of the hydrophobic effect. Our thermodynamic and structure-based analysis,
      together with corresponding theoretical studies, shows that none of the predicted
      binding steps can be considered as a rigid-body association. In this light we
      anticipate our thermodynamic approach to be the basis of more sophisticated
      nucleic acid recognition mechanisms, which take into account the dynamic nature
      of both the nucleic acid and the ligand molecule.

PMID- 18086707
TI  - Probing dynamics of HIV-1 nucleocapsid protein/target hexanucleotide complexes by
      2-aminopurine.
AB  - The nucleocapsid protein (NC) plays an important role in HIV-1, mainly through
      interactions with the genomic RNA and its DNA copies. Though the structures of
      several complexes of NC with oligonucleotides (ODNs) are known, detailed
      information on the ODN dynamics in the complexes is missing. To address this, we
      investigated the steady state and time-resolved fluorescence properties of 2
      aminopurine (2Ap), a fluorescent adenine analog introduced at positions 2 and 5
      of AACGCC and AATGCC sequences. In the absence of NC, 2Ap fluorescence was
      strongly quenched in the flexible ODNs, mainly through picosecond to nanosecond
      dynamic quenching by its neighboring bases. NC strongly restricted the ODN
      flexibility and 2Ap local mobility, impeding the collisions of 2Ap with its
      neighbors and thus, reducing its dynamic quenching. Phe(16)-->Ala and Trp(37)-
      >Leu mutations largely decreased the ability of NC to affect the local dynamics
      of 2Ap at positions 2 and 5, respectively, while a fingerless NC was totally
      ineffective. The restriction of 2Ap local mobility was thus associated with the
      NC hydrophobic platform at the top of the folded fingers. Since this platform
      supports the NC chaperone properties, the restriction of the local mobility of
      the bases is likely a mechanistic component of these properties.

PMID- 18086708
TI  - Structure-function analysis of the RNA helicase maleless.
AB  - Loss of function of the RNA helicase maleless (MLE) in Drosophila melanogaster
      leads to male-specific lethality due to a failure of X chromosome dosage
      compensation. MLE is presumably involved in incorporating the non-coding roX RNA
      into the dosage compensation complex (DCC), which is an essential but poorly
      understood requirement for faithful targeting of the complex to the X chromosome.
      Sequence comparison predicts several RNA-binding domains in MLE but their
      properties have not been experimentally verified. We evaluated the RNA-binding
      characteristics of these conserved motifs and their contributions to RNA
      stimulated ATPase activity, to helicase activity, as well as to the targeting of
      MLE to the nucleus and to the X chromosome territory. We find that RB2 is the
      dominant, conditional RNA-binding module, which is indispensable for ATPase and
      helicase activity whereas the N-terminal RB1 motif does not bind RNA, but is
      involved in targeting MLE to the X chromosome. The C-terminal domain containing a
      glycine-rich heptad repeat adds potential dimerization and RNA-binding surfaces
      which are not required for helicase activity.

PMID- 18086709
TI  - Diversity of preferred nucleotide sequences around the translation initiation
      codon in eukaryote genomes.
AB  - Understanding regulatory mechanisms of protein synthesis in eukaryotes is
      essential for the accurate annotation of genome sequences. Kozak reported that
      the nucleotide sequence GCCGCC(A/G)CCAUGG (AUG is the initiation codon) was
      frequently observed in vertebrate genes and that this 'consensus' sequence
      enhanced translation initiation. However, later studies using invertebrate,
      fungal and plant genes reported different 'consensus' sequences. In this study,
      we conducted extensive comparative analyses of nucleotide sequences around the
      initiation codon by using genomic data from 47 eukaryote species including
      animals, fungi, plants and protists. The analyses revealed that preferred
      nucleotide sequences are quite diverse among different species, but differences
      between patterns of nucleotide bias roughly reflect the evolutionary
      relationships of the species. We also found strong biases of A/G at position -3,
      A/C at position -2 and C at position +5 that were commonly observed in all
      species examined. Genes with higher expression levels showed stronger signals,
      suggesting that these nucleotides are responsible for the regulation of
      translation initiation. The diversity of preferred nucleotide sequences around
      the initiation codon might be explained by differences in relative contributions
      from two distinct patterns, GCCGCCAUG and AAAAAAAUG, which implies the presence
      of multiple molecular mechanisms for controlling translation initiation.

PMID- 18086711
TI  - Tetrameric restriction enzymes: expansion to the GIY-YIG nuclease family.
AB  - The GIY-YIG nuclease domain was originally identified in homing endonucleases and
      enzymes involved in DNA repair and recombination. Many of the GIY-YIG family
      enzymes are functional as monomers. We show here that the Cfr42I restriction
      endonuclease which belongs to the GIY-YIG family and recognizes the symmetric
      sequence 5'-CCGC/GG-3' ('/' indicates the cleavage site) is a tetramer in
      solution. Moreover, biochemical and kinetic studies provided here demonstrate
      that the Cfr42I tetramer is catalytically active only upon simultaneous binding
      of two copies of its recognition sequence. In that respect Cfr42I resembles the
      homotetrameric Type IIF restriction enzymes that belong to the distinct PD
      (E/D)XK nuclease superfamily. Unlike the PD-(E/D)XK enzymes, the GIY-YIG nuclease
      Cfr42I accommodates an extremely wide selection of metal-ion cofactors, including
      Mg2+, Mn2+, Co2+, Zn2+, Ni2+, Cu2+ and Ca2+. To our knowledge, Cfr42I is the
      first tetrameric GIY-YIG family enzyme. Similar structural arrangement and
      phenotypes displayed by restriction enzymes of the PD-(E/D)XK and GIY-YIG
      nuclease families point to the functional significance of tetramerization.

PMID- 18086710
TI  - Dlx2 homeobox gene transcriptional regulation of Trkb neurotrophin receptor
      expression during mouse retinal development.
AB  - Dlx homeobox genes are first expressed in embryonic retina at E11.5. The
      Dlx1/Dlx2 null retina has a reduced ganglion cell layer (GCL), with loss of late
      born differentiated retinal ganglion cells (RGCs) due to increased apoptosis.
      TrkB signaling is proposed to regulate the dynamics of RGC apoptosis throughout
      development. DLX2 expression markedly precedes the onset of TrkB expression in
      the GCL; TrkB co-expression with Dlx2 and RGC markers is well-established by
      E13.5. In the Dlx1/Dlx2 null retina, TrkB expression is significantly reduced by
      E16.5. We demonstrated that DLX2 binds to a specific region of the TrkB promoter
      in retinal neuroepithelium during embryogenesis. In vitro confirmation and the
      functional consequences of DLX2 binding to this TrkB regulatory region support
      TrkB as a Dlx2 transcriptional target. Furthermore, ectopic Dlx2 expression in
      retinal explants activates TrkB expression and Dlx2 knockdown in primary retinal
      cultures results in reduced TrkB expression. RGC differentiation and survival
      require the coordinated expression of transcription factors. This study
      establishes a direct transcriptional relationship between a homeodomain protein
      involved in RGC differentiation and a neurotrophin receptor implicated in RGC
      survival. Signaling mediated by TrkB may contribute to survival of late-born RGCs
      whose terminal differentiation is regulated by Dlx gene function.

PMID- 18086713
TI  - The impact of Juvenile Huntington's Disease on the family: the case of a rare
      childhood condition.
AB  - There has been little research into the impact of Juvenile Huntington's Disease
      (JHD) on the family, and the issues facing this group are poorly understood. The
      study reported here is part of larger project that aimed to address this. Ten
      semi-structured interviews with the main carer were carried out, and were
      analysed using Interpretative Phenomenological Analysis (IPA). This article
      reports three themes arising from the study relating to the psychosocial impact
      of JHD on the family: (1) dealing with something so different; (2) lack of
      understanding (3) isolation. This information is useful in developing appropriate
      services for families affected by JHD, as well as being of relevance to other
      childhood conditions.

PMID- 18086712
TI  - The cucumovirus 2b gene drives selection of inter-viral recombinants affecting
      the crossover site, the acceptor RNA and the rate of selection.
AB  - RNA-RNA recombination is an important pathway in virus evolution and has been
      described for many viruses. However, the factors driving recombination or
      promoting the selection of recombinants are still unclear. Here, we show that the
      small movement protein (2b) was able to promote selection of RNA 1/2-RNA 3
      recombinants within a chimeric virus having RNAs 1 and 2 from cucumber mosaic
      virus, and RNA 3 from the related tomato aspermy virus, along with heterologous
      2b genes. The source of the 2b also determined the selection of the acceptor RNA
      and the crossover site, as well as affecting the rate of selection of the
      recombinant RNAs. The nature of the RNA 3 also influenced the selection of the
      recombinant RNAs. A 163-nt tandem repeat in RNA 3 significantly affected the rate
      of selection of the recombinant RNA, while a single nucleotide within the repeat
      affected the crossover site. The recombination occurred in a non-random manner,
      involved no intermediates and probably was generated via a copy-choice mechanism
      during (+) strand RNA synthesis.

PMID- 18086714
TI  - Resilient coping: applying adaptive responses to prior adversity during treatment
      for hepatitis C infection.
AB  - Social marginalization is associated with poor health outcomes for affected
      people. However, in a psychosocial study of treatment for hepatitis C infection
      conducted in Sydney, Australia, participants living in socially disadvantaged
      circumstances applied adaptive approaches learned from past experiences of drug
      dependence, living with symptoms of chronic illness, coping with depression and
      childhood sexual abuse to enable them to cope with severe treatment-related side
      effects. This finding has implications for the clinical management of hepatitis C
      treatment; the factors and processes that facilitate adaptive coping to adversity
      associated with social marginalization can be assessed for their clinical
      contribution to coping with an arduous regimen.

PMID- 18086715
TI  - Health-related information processing and recent health problems: evidence from a
      modified stroop task.
AB  - Our purpose was to assess the relationship between health status and health
      related information processing. We expected that persons who report a recent
      health problem would show greater bias towards relevant stimuli. Participants
      comprised two groups: the experimental with 25 students who recently had to
      interrupt usual activities because of their health, and a comparison group of 25
      healthy students matched for demographics, health habits and current health.
      Using an emotional Stroop task, the experimental group demonstrated enhanced
      interference effects for illness and health-related versus general threat and
      neutral words. Satisfaction with life impacted the processing of health and
      illness-related stimuli.

PMID- 18086716
TI  - Social support and depression among bone marrow transplant patients.
AB  - This study considered the role of social support in mitigating depression among
      bone marrow transplant (BMT) patients. Eighty-six BMT patients completed the
      Medical Outcomes Study Social Support Scale (MOS-SSS) and the Centers for
      Epidemiological Studies of Depression Scale (CES-D) before transplant and again
      at one year posttransplant. Results showed moderate levels of depressive symptoms
      in BMT patients, with 29.1 percent and 27.6 percent meeting the suggested
      criterion for clinical depression at pre-BMT and one year post-BMT, respectively.
      Overall, patients experienced a reduced level of depression post-BMT, although
      females reported more depression than males. Social support pre-BMT predicted
      depression levels post-BMT controlling for initial levels of depression. Clinical
      implications for health care providers working with cancer patients and their
      families are discussed.

PMID- 18086717
TI  - Not just 'skin deep': psychosocial effects of dermatological-related social
      anxiety in a sample of acne patients.
AB  - This study examined links between anxiety pertaining to having one's skin
      evaluated by others and intention to participate in sport/exercise, general self
      esteem and dermatological quality of life. Data assessing dermatological-related
      social anxiety, perceived acne severity, intention to participate in
      sport/exercise, self-esteem and dermatological quality of life were obtained from
      50 acne patients. Results showed dermatological-related social anxiety to be
      negatively associated with intention to participate in sport/exercise, self
      esteem and dermatological quality of life. The relationship between patient-rated
      acne severity and outcome variables was found to be partially mediated by
      reported levels of dermatological-related social anxiety. The current findings
      suggest that how one perceives their skin to be evaluated by others has
      implications for self-perceptions and may act as a barrier to sport/exercise
      participation.

PMID- 18086718
TI  - Is disturbed sleep a mediator in the association between social support and
      myocardial infarction?
AB  - The objective of this study was to investigate a mediating relationship between
      social support and disturbed sleep in cases surviving myocardial infarction. The
      case-referent studies, Stockholm Heart Epidemiological Program (SHEEP) and
      Vasternorrland Heart Epidemiological Program (VHEEP) were used comprising 6231
      participants (2046 women). Referents were randomly selected. Disturbed sleep was
      operationalized by the Karolinska Sleep Questionnaire, network support by the
      Availability of Social Integration Index and emotional support by the
      Availability of Attachment Index. Mediating associations were tested with
      logistic regression. The results show that disturbed sleep may act as a mediator
      between low network support and myocardial infarction in women.

PMID- 18086719
TI  - Three ways of talking about health in communities targeted for regeneration:
      interviews with community professionals.
AB  - Interviews were held with nine peripatetic professionals-district nurses, health
      visitors and social workers-working in New Deal for Communities (NDC) urban areas
      in the English West Midlands. They spoke of health in the community in three
      distinct ways: health as individual and family lifestyle; the local environment
      and health; and ;life is a struggle for some'. Those who emphasized the
      individual and family lifestyle approach expressed frustration in their
      professional role. The two alternative discourses, while recognizing the
      influence of social determinants of health, were problematic in different ways,
      reflecting the lack of a clear alternative to the individual and family lifestyle
      model for public health professions.

PMID- 18086720
TI  - Longitudinal risk factors for adverse psychological functioning six months after
      coronary artery bypass graft surgery.
AB  - This research aimed to identify modifiable risk factors for poor psychological
      functioning six months post-operatively, using a chronic illness model to explain
      the relationships between risk factors. Consecutive elective CABG patients (N =
      119) completed self-report measures including optimism, illness representations,
      self-rated health, social support, coping methods, depression, anxiety and PTSD
      symptomatology in a repeated measures design. Poor pre-operative psychological
      functioning was the strongest psychological risk factor for adverse psychological
      functioning six months post-operatively. Longitudinal support for the chronic
      illness model examined was limited. Further research to identify modifiable risk
      factors and pre-operative psychopathology screening to determine individuals at
      risk of poor psychological outcome is recommended.

PMID- 18086721
TI  - Making sense of illness or disability: the nature of sense making in multiple
      sclerosis (MS).
AB  - This study investigated sense making in multiple sclerosis (MS) and relations
      with illness, religious-spiritual beliefs and adjustment (life satisfaction,
      positive states of mind, depression, anxiety). Four hundred and eight persons
      with MS completed a questionnaire. Half the sample generated sense making
      explanations for their illness. Content analyses revealed 16 sense making themes.
      Participants who reported having a religious-spiritual belief were more likely to
      report sense making than those who did not have such a belief. Sense making was
      related to lower disability and disease severity and evidenced beneficial direct
      effects on positive adjustment outcomes and depression after controlling for
      illness and religious-spiritual belief.

PMID- 18086722
TI  - Older women and everyday talk about the ageing body.
AB  - This discourse analytic study shows how 10 older women, who exercise regularly or
      attend the University of the Third Age, adjust to the ageing body in their
      ;everyday talk' through taking a dualist position. The part of the body which is
      discursively constructed as ageing becomes objectified through appealing to a
      wider cultural discourse of ageing as biological decline. This dualist position
      is embedded within a wider cultural discourse of personal agency. The
      individual's control of the ageing body is emphasized, the ability to monitor and
      manage ;ageing body parts' through exerting the ;active mind' and the ;busy body'
      in activities, or simply focusing on ;looking good'.

PMID- 18086723
TI  - Youth and adolescent physical activity lapsers: examining self-efficacy as a
      mediator of the relationship between family social influence and physical
      activity.
AB  - The present study examined whether self-efficacy mediates the relationship
      between family social influence and physical activity among youth who have
      experienced a recent lapse in their physical activity participation. Using a
      prospective, longitudinal design, participants completed measures of social
      influence, self-regulatory efficacy and physical activity. Only those
      participants whose physical activity declined were retained for further analysis.
      Self-regulatory efficacy partially mediated the relationship between family
      social influence and physical activity, with self-efficacy mediating 36 percent
      of the total effect. The results provide support for self-regulatory efficacy as
      a mediator and provide preliminary insight into the potential mechanisms for
      preventing lapses in activity from developing into prolonged periods of
      inactivity within this population.

PMID- 18086724
TI  - Effects of weight stigma on exercise motivation and behavior: a preliminary
      investigation among college-aged females.
AB  - This study examined the relation between weight stigma, exercise motivation and
      exercise behavior. One hundred female undergraduates (BMIs [kg/m(2)] 17-38)
      completed measures of experiences with weight stigma, body dissatisfaction, self
      esteem and exercise motivation, and reported on their exercise behavior. Stigma
      experiences were positively correlated with BMI and body dissatisfaction.
      Importantly, stigma experiences were related to increased desire to avoid
      exercise, even when controlling for BMI and body dissatisfaction. Exercise
      avoidance was in turn related to less frequent strenuous and moderate exercise.
      These findings suggest that weight stigma (through its impact on avoidance
      motivation) could potentially decrease physical activity levels.

PMID- 18086726
TI  - A double-blind placebo controlled trial of etanercept in patients with giant cell
      arteritis and corticosteroid side effects.
AB  - OBJECTIVE: Open label studies have suggested that tumour necrosis factor (TNF)
      antagonists led to sustained improvement and corticosteroid sparing effect in
      patients with giant cell arteritis (GCA). To confirm these observations, we
      conducted a randomised, double-blind, placebo controlled trial with etanercept in
      patients with biopsy-proven GCA with side effects secondary to corticosteroids.
      METHODS: We randomly assigned patients with GCA to receive etanercept (n = 8) or
      placebo (n = 9) over 1 year together with corticosteroids that were reduced
      according to a predefined schedule. The primary outcome was the ability to
      withdraw the corticosteroid therapy and control the disease activity at 12
      months. RESULTS: Baseline characteristics were similar in the two groups,
      although patients in the etanercept group showed higher levels of basal glycaemia
      (p = 0.02) and a higher erythrocyte sedimentation rate (ESR) (p = 0.01). After 12
      months, 50% of the patients in the etanercept group and 22.2% in the placebo
      group were able to control the disease without corticosteroid therapy (p value
      not significant). Patients in the etanercept group had a significant lower dose
      of accumulated prednisone during the first year of treatment (p = 0.03). There
      were no differences in the number and type of adverse events. CONCLUSION: The
      limited number of patients included in this study does not allow us to draw
      definitive conclusions. Etanercept therapy was well tolerated in this aged
      population. The therapeutic role of etanercept in patients with GCA should be
      evaluated in studies with a larger number of patients.

PMID- 18086727
TI  - Abatacept inhibits progression of structural damage in rheumatoid arthritis:
      results from the long-term extension of the AIM trial.
AB  - OBJECTIVE: Assess the effect of abatacept on progression of structural damage
      over 2 years in patients with rheumatoid arthritis who had an inadequate response
      to methotrexate. METHODS: 539 patients entered an open-label extension of the AIM
      (Abatacept in Inadequate responders to Methotrexate) trial and received
      abatacept. Radiographic assessment of the hands and feet was performed at
      baseline, year 1 and year 2. At year 2, each patient's radiographs were scored
      for progression blinded to sequence and treatment allocation. RESULTS: In
      patients treated with abatacept for 2 years, greater reduction in progression of
      structural damage was observed in year 2 than in year 1. The mean change in total
      Genant-modified Sharp scores was reduced from 1.07 units in year 1 to 0.46 units
      in year 2. Similar reductions were observed in erosion and joint space narrowing
      scores. Following 2 years of treatment with abatacept, 50% of patients had no
      progression of structural damage as defined by a change in the total score of <
      or =0 compared with baseline. 56% of patients treated with abatacept had no
      progression during the first year compared with 45% of patients treated with
      placebo. In their second year of treatment with abatacept, more patients had no
      progression than in the first year (66% vs 56%). CONCLUSIONS: Abatacept has a
      sustained effect that inhibits progression of structural damage. Furthermore, the
      mean change in radiographic progression in patients treated with abatacept for 2
      years was significantly lower in year 2 versus year 1, suggesting that abatacept
      may have an increasing disease-modifying effect on structural damage over time.

PMID- 18086728
TI  - A novel TNFRSF1A splice mutation associated with increased nuclear factor kappaB
      (NF-kappaB) transcription factor activation in patients with tumour necrosis
      factor receptor associated periodic syndrome (TRAPS).
AB  - OBJECTIVE: To characterise and investigate the functional consequences of a novel
      TNFRSF1A splice site mutation causing tumour necrosis factor receptor associated
      periodic syndrome (TRAPS) in a 16-year-old male patient and his mother. METHODS:
      Mutational DNA screening was performed in the patient and his mother. Western
      blotting was used to analyse protein expression levels of TNFR1. A multiplex bead
      immunoassay was used to quantify serum levels of range of cytokines, and an ELISA
      based transcription factor assay to measure nuclear factor (NF)-kappaB
      transactivation. Serum levels of soluble TNFR1 (sTNFR1) were measured by ELISA
      and fluorescence-activated cell sorting (FACS) analysis used to measure monocyte
      TNFR1 cell surface expression. RESULTS: A novel mutation, c.472+1G>A
      (C158delinsYERSSPEAKPSPHPRG), involving a splice site in intron 4 of TNFRSF1A,
      was found in the proband and affected mother leading to a 45 nucleotide insertion
      of intronic DNA into the mRNA, resulting in an in-frame insertion of 15 amino
      acids in the mature TNFR1 protein and a deletion of a cysteine residue C129 (158)
      in cysteine rich domain (CRD)3. The patients had reduced serum sTNFR1 and surface
      expression levels of TNFR1, with marked increases in pro- and anti-inflammatory
      cytokine. Their peripheral blood mononuclear cells (PBMC) had increased basal NF
      kappaB activation compared with healthy controls and also had increased p50
      nuclear expression following tumour necrosis factor (TNF) stimulation compared
      with PBMC from healthy controls, as well as T50M (T79M) and C88R (C117R) patients
      with TRAPS and patients with rheumatoid arthritis (RA). CONCLUSION: A novel,
      TRAPS causing, TNFRSF1A splice site mutation is associated with decreased sTNFR1
      levels, cell surface and whole cell extract expression and increased NF-kappaB
      transcription factor activation.

PMID- 18086729
TI  - Care of the mentally ill in prisons: challenges and solutions.

PMID- 18086730
TI  - Introduction to: resource document on the use of restraint and seclusion in
      correctional mental health care.

PMID- 18086731
TI  - Resource document on the use of restraint and seclusion in correctional mental
      health care.
AB  - This resource document discusses the use of seclusion or restraint for purposes
      of mental health intervention in correctional facilities. Correctional mental
      health standards essentially state that seclusion or restraint, when used for
      health care purposes, should be implemented in a manner consistent with current
      community practice. The community practice was significantly impacted and revised
      during July 1999, after the Health Care Financing Administration defined rules
      for the use of seclusion and restraint in facilities that participate in Medicare
      and Medicaid. Since few correctional facilities are Medicare or Medicaid
      participants, these rules had little impact on the use of seclusion or restraint
      for mental health care purposes in correctional systems. Consequently, many
      correctional health care systems have not developed policies, procedures, or
      practices that are consistent with current community practice. This document
      provides guidance in remedying such problems, with a focus on areas relevant to
      timeframes, settings, and monitoring.

PMID- 18086732
TI  - Commentary: seclusion and restraint in corrections a time for change.
AB  - Seclusion and restraint are essential interventions in the acute psychiatric care
      of patients in correctional environments. When administered and monitored
      properly, they are safe and effective in reducing the risk of harm. However,
      correctional systems have not developed uniform practices that are consistent
      with current community standards. There has been no clear national standard of
      care for the use of seclusion and restraint in correctional mental health care.
      The need for a national standard of care is discussed, and sources for developing
      a standard of care are reviewed. The Resource Document produced by the American
      Psychiatric Association is presented as a significant step toward establishing a
      national standard of care.

PMID- 18086733
TI  - Commentary: the use of restraint and seclusion in correctional mental health.
AB  - In contrast to the position taken in the American Psychiatric Association's
      "Resource Document on The Use of Restraint and Seclusion in Correctional Mental
      Health Care," this commentary proposes limiting the use of mental health
      restraints to the stabilization of unsafe situations during the time it takes to
      transfer an inmate to a psychiatric hospital. Jails and prisons are inherently
      nontherapeutic environments and are not adequate settings for managing mental
      health emergencies, such as those that require the use of restraints.
      Correctional conditions often contribute to the onset, and impede the resolution,
      of the underlying mental health crisis. Attempts to contain mental health
      emergencies in a correctional setting with an expanded use of restraints can
      compromise clinical care, overlook the root cause of many crises, impair the role
      of mental health professionals by blurring the distinction between mental health
      and security staff, and can lead to a deterioration in the standards of care.

PMID- 18086734
TI  - Commentary: evolving toward equivalency in correctional mental health care--a
      view from the maximum security trenches.
AB  - Developing and implementing community standards of care in correctional mental
      health and psychiatric practice will facilitate progress toward attaining
      equivalency in care in prisons and jails. Specialized therapeutic procedures such
      as application of restraints and seclusion when properly implemented are valuable
      tools in the treatment of the chronically mentally ill in prisons. The authors
      share some useful points for working in maximum-security prisons.

PMID- 18086735
TI  - Commentary: a British perspective on the use of restraint and seclusion in
      correctional mental health care.
AB  - Policy and practice in the safe management of disturbed and violent behavior as
      applied in USA and UK correctional facilities is examined in this article.
      Certain differences emerge and are discussed, particularly relating to physical
      restraint. The paucity of evidence to support particular interventions is
      highlighted through a review of a UK systematic analysis of world literature on
      best practice.

PMID- 18086736
TI  - Sex offenders and insanity: an examination of 42 individuals found not guilty by
      reason of insanity.
AB  - Although currently there is a large body of research on the characteristics and
      treatment of sex offenders, very little research has been conducted to
      investigate the characteristics of sex offenders who have been adjudicated
      insane. This study included 42 patients at Napa State Hospital who were
      adjudicated not guilty by reason of insanity (NGRI) for a sex offense. The sample
      was further divided into offenders whose victims were children and those whose
      victims were adults. Data were collected with a structured chart review
      instrument. A large percentage of the sex offenders received a primary diagnosis
      of schizophrenia or schizoaffective disorder, and many had a comorbid substance
      use disorder. The high percentage of sex offenders in the current study with
      diagnosed schizophrenia or schizoaffective disorder may represent a previously
      unstudied subgroup of sex offenders. An alternative explanation is that the
      experts did not evaluate substance use and intoxication adequately, assess for
      malingering, or apply the proper legal standard for insanity.

PMID- 18086737
TI  - Commentary: sex offenders and insanity.
AB  - Sex offenders with a psychotic illness present challenges in the determination of
      criminal responsibility, risk assessment, and psychiatric treatment. Novak et al.
      present data that raise concerns regarding how forensic psychiatrists could
      conclude sex offenders were not responsible for their offenses in the absence of
      clear evidence of psychotic symptoms at the time of assessment and/or offense.
      They also highlight issues of risk assessment and management of psychotic sex
      offenders that have not been adequately studied. We require further research of
      psychotic sex offenders to be able to offer scientifically supported opinions on
      risk assessment to courts and decision-makers.

PMID- 18086738
TI  - Predicting the likelihood of future sexual recidivism: pilot study findings from
      a California sex offender risk project and cross-validation of the Static-99.
AB  - Pilot findings on 137 California sex offenders followed up over 10 years after
      release from custody (excluding cases in which legal jurisdiction expired) are
      presented. The sexual recidivism rate, very likely inflated by sample selection,
      was 31 percent at five years and 40 percent at 10 years. Cumulatively, markers of
      sexual deviance (multiple victim types) and criminality (prior parole violations
      and prison terms) led to improved prediction of sexual recidivism (receiver
      operating characteristic [ROC] = .71, r = .46) than singly (multiple victim
      types: ROC = .60, r = .31; prior parole violations and prison terms: ROC = .66, r
      = .37). Long-term Static-99 statistical predictive accuracy for sexual recidivism
      was lower in our sample (ROC = .62, r =.24) than the values presented in the
      developmental norms. Sexual recidivism rates were higher in our study for Static
      99 scores of 2 and 3 than in the developmental sample, and lower for scores of 4
      and 6. Given failures to replicate developmental norms, the Static-99 method of
      ranking sexual recidivism risk warrants caution when applied to individual
      offenders.

PMID- 18086739
TI  - Amnesia and crime.
AB  - Amnesia for serious offenses has important legal implications, particularly
      regarding its relevance in the contexts of competency to stand trial and criminal
      responsibility. Forensic psychiatrists and other mental health professionals are
      often required to provide expert testimony regarding amnesia in defendants.
      However, the diagnosis of amnesia presents a challenge, as claims of memory
      impairment may stem from organic disease, dissociative amnesia, amnesia due to a
      psychotic episode, or malingered amnesia. We review the theoretical, clinical,
      and legal perspectives on amnesia in relation to crime and present relevant cases
      that demonstrate several types of crime-related amnesia and their legal
      repercussions. Consideration of the presenting clinical features of crime-related
      amnesia may enable a fuller understanding of the different types of amnesia and
      assist clinicians in the medico-legal assessment and diagnosis of the claimed
      memory impairment. The development of a profile of aspects characteristic of
      crime-related amnesia would build toward establishing guidelines for the
      assessment of amnesia in legal contexts.

PMID- 18086740
TI  - The use of telemedicine to evaluate competency to stand trial: a preliminary
      randomized controlled study.
AB  - To investigate whether forensic evaluations can be performed reliably using
      telemedicine, we compared the results on a standard competency assessment
      instrument using telemedicine (TM) and live interviews (LI). Two board-certified
      forensic psychiatrists used the Georgia Court Competency Test (GCCT) to evaluate
      21 forensic psychiatric inpatients. Half of the patients were randomly assigned
      to a telemedicine interview and half were assigned to a live interview. Total
      scores on the GCCT were similar for both raters, indicating high levels of
      agreement between telemedicine and live interviews. Patient and provider
      satisfaction were measured and indicated that, although patients did not express
      a preference for a particular interview modality, providers reported greater
      satisfaction with live interviews. Findings suggest that one aspect of competency
      to stand trial can be reliably evaluated using telemedicine and that patients
      perceive telemedicine as an acceptable alternative to a standard live interview.
      The limited sample size precludes definite conclusions and further studies
      involving a larger forensic study population are warranted.

PMID- 18086741
TI  - Current and lifetime psychiatric illness among inmates not identified as acutely
      mentally ill at intake in Connecticut's jails.
AB  - This study presents estimates of current and lifetime psychiatric illness among
      inmates not identified as acutely mentally ill at intake into all five of
      Connecticut's adult jails (four male facilities and one female facility).
      Diagnoses were assessed with the Structured Clinical Interview for DSM-IV (SCID),
      Clinician-Administered PTSD Scale, and the Global Assessment of Functioning (GAF)
      and are reported by gender and race/ethnicity. The results showed that more than
      two of three inmates met the criteria for at least one lifetime psychiatric
      disorder, almost half for an anxiety disorder, and more than one-third for an
      affective disorder. Overall, estimates of psychiatric morbidity in the women were
      higher than those in the men, with the exception of antisocial personality
      disorder (ASPD). Of particular note, borderline personality disorder was
      diagnosed in 23.2 percent of women and 12.9 percent of men. An allegation of a
      violent offense was not associated with the presence of mental illness or with a
      specific diagnosis. Lifetime history of any mental illness was associated with
      significantly reduced scores (range, 12-15 points reduction) on the Global
      Assessment of Functioning. The study showed that current and lifetime psychiatric
      morbidity are elevated among newly incarcerated adults who do not exhibit obvious
      signs of severe mental illness and are associated with functional impairment.
      While such disorders do not necessarily require treatment, unrecognized mental
      illness may place offenders at greater risk while incarcerated than offenders
      without mental illness. This study reinforces the need for appropriate screening
      and referral for treatment at intake into jail.

PMID- 18086742
TI  - AAPL Practice Guideline for the Forensic Psychiatric Evaluation of Competence to
      Stand Trial: an English legal perspective.
AB  - This brief commentary compares the law relating unfitness to plead in England and
      Wales with that of competency to stand trial, as reflected in the AAPL Practice
      Guideline. In so doing, it presents the argument that English law, with its
      adherence to a test of unfitness that goes back to the first half of the 19th
      century, may no longer be fit for the purpose. Unlike the test for incompetency
      to stand trial adopted by most of the United States, English law fails to
      incorporate decisional competence and consequently may be failing to protect
      vulnerable defendants. The commentary concludes that, despite the differences in
      law and practice between our respective countries, the AAPL Guideline contains
      much of value for psychiatrists and lawyers who have to deal with unfitness to
      plead, an area of the law that surely ought to be the subject of consideration
      for reform.

PMID- 18086743
TI  - AAPL Practice Guideline for the Forensic Psychiatric Evaluation of Competence to
      Stand Trial: a Canadian legal perspective.
AB  - Canadian legal tests of fitness to stand trial, while similar to tests in the
      United States, place less emphasis on rational understanding of the complexities
      of the trial process and greater emphasis on communicating with legal counsel.
      The limited cognitive capacity test has gained wide acceptance in Canadian
      jurisprudence as a balance between ensuring that an accused person can provide
      the necessary information to allow his legal counsel to defend him adequately
      while also minimizing the potential delay in a speedy trial. The tests have been
      criticized by organized psychiatry and legal scholars but have been supported by
      advocacy groups for the mentally ill. Canadian research on accused persons
      committed to hospitals for fitness evaluations suggests that this process may be
      used or, arguably, misused by psychiatrists to provide treatment to persons who
      would otherwise be inaccessible to psychiatric intervention. This raises complex
      ethics-related questions not yet fully addressed.

PMID- 18086744
TI  - AAPL Practice Guideline for the Forensic Psychiatric Evaluation of Competence to
      Stand Trial: an American legal perspective.
AB  - The AAPL Practice Guideline for the Forensic Psychiatric Evaluation of Competence
      to Stand Trial provides a rich discussion of the legal standards and procedures
      for evaluating and determining a criminal defendant's trial competence and for
      restoring to competence defendants found to be incompetent. The document includes
      an up-to-date discussion of the applicable case law, examines ethics
      considerations for forensic examiners, addresses cultural issues, and offers
      practical templates for interviewing defendants and preparing reports. Although
      its focus is on trial competence in adult criminal court, the document also
      attends to competency considerations for minors facing delinquency proceedings in
      juvenile court. Comprehensive and incisive, if not optimally organized and
      tabulated, the Guideline will serve as the standard reference for psychiatrists
      asked to provide trial competence assessments in criminal and juvenile court
      cases.

PMID- 18086745
TI  - Common pitfalls in the evaluation of testamentary capacity.
AB  - The examination for testamentary capacity poses several unique challenges to the
      forensic evaluator, especially when performed, as is often the case, postmortem.
      Forensic experience reveals that a series of common pitfalls awaits the unwary
      witness. This brief review identifies the more common pitfalls and suggests how
      to avoid them.

PMID- 18086746
TI  - Cognitive dysfunction and competency restoration: using cognitive remediation to
      help restore the unrestorable.
AB  - The goal of this article is to present an argument for using cognitive
      remediation as an adjunctive form of treatment in competency restoration
      programs. Clinically, it has been generally agreed that the Dusky standard
      requires a functional analysis of the defendant's current capacities in the
      current legal context; merely having a mental illness does not mean incompetency.
      Based on the recent literature that describes the neuropsychological deficits
      associated with major psychiatric illnesses such as schizophrenia, bipolar
      disorder, and depression, it is believed that many psychiatrically ill patients
      are hindered from returning to the legal process by their inability to understand
      and acquire the information necessary to be found competent. We argue that
      cognitive remediation would serve as a helpful form of treatment for incompetent
      patients to improve their cognitive functioning and consequently, their
      likelihood of being found competent.

PMID- 18086747
TI  - Alien associations.
AB  - This story is a highly fictionalized account of events that took place during a
      year of Fellowship in Forensic Psychiatry, 1997-1998, at the Yale University
      School of Medicine, Division of Psychiatry and the Law. It is dedicated to my co
      fellow, Theresa Stathas, MD, whose kindness, warmth, and support were appreciated
      during my fellowship year. She generously provided me with alien-themed items,
      such as a ballpoint pen decorated with 23 alien heads and 56 alien eyes,
      throughout that year.

PMID- 18086748
TI  - "The street will drive you crazy": why homeless psychotic women in the
      institutional circuit in the United States often say no to offers of help.
AB  - Many people who struggle with psychotic disorder often refuse offers of help,
      including housing, extended by mental health services. This article uses the
      ethnographic method to examine the reasons for such refusal among women who are
      homeless and psychiatrically ill in the institutional circuit in an urban area of
      Chicago. It concludes that such refusals arise not only from a lack of insight
      but also from the local culture's ascription of meaning to being "crazy." These
      data suggest that offers of help-specifically, diagnosis-dependent housing-to
      those on the street may be more successful when explicit psychiatric diagnosis is
      downplayed.

PMID- 18086750
TI  - Ethnic density of neighborhoods and incidence of psychotic disorders among
      immigrants.
AB  - OBJECTIVE: A high incidence of psychotic disorders has been reported in immigrant
      ethnic groups in Western Europe. Some studies suggest that ethnic density may
      influence the incidence of schizophrenia. The authors investigated whether this
      increased incidence among immigrants depends on the ethnic density of the
      neighborhoods in which they live. METHOD: This was a prospective first-contact
      incidence study of psychotic disorders in The Hague, by ethnicity and
      neighborhood of residence. Over a 7-year period, individuals who made contact
      with a physician for a suspected psychotic disorder underwent diagnostic
      interviews and received DSM-IV diagnoses. A comprehensive municipal registration
      system provided the denominator for incidence rates. Data were sufficient to
      examine incidence rates in native Dutch and in first- and second-generation
      immigrants from Morocco, Suriname, and Turkey. The ethnic density of a
      neighborhood was computed for each immigrant group as the proportion of residents
      belonging to that group. Multilevel regression analyses predicted the incidence
      of psychotic disorders as a function of individual ethnicity and neighborhood
      ethnic density. Models were fitted for all immigrants together and for each
      immigrant group separately. RESULTS: A total of 226 native Dutch and 240
      immigrants were diagnosed as having a psychotic disorder. Compared with native
      Dutch, the adjusted incidence rate ratio for immigrants was significantly
      increased in low-ethnic-density neighborhoods (2.36) but not in high-ethnic
      density neighborhoods (1.25). There was a strong interaction between individual
      ethnicity and neighborhood ethnic density as predictors of incidence of illness.
      These findings were consistent across all immigrant groups. CONCLUSIONS: The
      incidence of psychotic disorders was elevated most significantly among immigrants
      living in neighborhoods where their own ethnic group comprised a small proportion
      of the population.

PMID- 18086749
TI  - Disruption of existing mental health treatments and failure to initiate new
      treatment after Hurricane Katrina.
AB  - OBJECTIVE: The authors examined the disruption of ongoing treatments among
      individuals with preexisting mental disorders and the failure to initiate
      treatment among individuals with new-onset mental disorders in the aftermath of
      Hurricane Katrina. METHODS: English-speaking adult Katrina survivors (N=1,043)
      responded to a telephone survey administered between January and March of 2006.
      The survey assessed posthurricane treatment of emotional problems and barriers to
      treatment among respondents with preexisting mental disorders as well as those
      with new-onset disorders posthurricane. RESULTS: Among respondents with
      preexisting mental disorders who reported using mental health services in the
      year before the hurricane, 22.9% experienced reduction in or termination of
      treatment after Katrina. Among those respondents without preexisting mental
      disorders who developed new-onset disorders after the hurricane, 18.5% received
      some form of treatment for emotional problems. Reasons for failing to continue
      treatment among preexisting cases primarily involved structural barriers to
      treatment, while reasons for failing to seek treatment among new-onset cases
      primarily involved low perceived need for treatment. The majority (64.5%) of
      respondents receiving treatment post-Katrina were treated by general medical
      providers and received medication but no psychotherapy. Treatment of new-onset
      cases was positively related to age and income, while continued treatment of
      preexisting cases was positively related to race/ethnicity (non-Hispanic whites)
      and having health insurance. CONCLUSIONS: Many Hurricane Katrina survivors with
      mental disorders experienced unmet treatment needs, including frequent
      disruptions of existing care and widespread failure to initiate treatment for new
      onset disorders. Future disaster management plans should anticipate both types of
      treatment needs.

PMID- 18086751
TI  - Selected infectious agents and risk of schizophrenia among U.S. military
      personnel.
AB  - OBJECTIVE: A number of studies have reported associations between Toxoplasma
      gondii (T. gondii) infection and the risk of schizophrenia. Most existing studies
      have used small populations and postdiagnosis specimens. As part of a larger
      research program, the authors conducted a hypothesis-generating case control
      study of T. gondii antibodies among individuals discharged from the U.S. military
      with a diagnosis of schizophrenia and serum specimens available from both before
      and after diagnosis. METHOD: The patients (N=180) were military members who had
      been hospitalized and discharged from military service with a diagnosis of
      schizophrenia. Healthy comparison subjects (3:1 matched on several factors) were
      members of the military who were not discharged. The U.S. military routinely
      collects and stores serum specimens of military service members. The authors used
      microplate-enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels
      to T. gondii, six herpes viruses, and influenza A and B viruses and
      immunoglobulin M (IgM) antibody levels to T. gondii in pre- and postdiagnosis
      serum specimens. RESULTS: A significant positive association between the T.
      gondii IgG antibody and schizophrenia was found; the overall hazard ratio was
      1.24. The association between IgG and schizophrenia varied by the time between
      the serum specimen collection and onset of illness. CONCLUSION: The authors found
      significant associations between increased levels of scaled T. gondii IgG
      antibodies and schizophrenia for antibodies measured both prior to and after
      diagnosis.

PMID- 18086752
TI  - EGFR and PDGFR differentially promote growth in malignant epithelioid
      mesothelioma of short and long term survivors.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is an asbestos related tumour
      difficult to detect early and treat effectively. Asbestos causes genetic
      modifications and cell signalling events that favour the resistance of MPM to
      apoptosis and chemotherapy. Only a small number of patients, approximately 10%,
      survive more than 3 years. The aim of our study was to assess possible
      differences within signalling pathways between short term survivors (survival <3
      years; STS) and long term survivors (survival >3 years; LTS) of MPM. METHODS: 37
      antibodies detecting proteins engaged in cell signalling pathways, enforcing
      proliferation, antiapoptosis, angiogenesis and other cellular activities were
      investigated by tissue microarray (TMA) technology. RESULTS: Epidermal growth
      factor receptor (EGFR) was expressed stronger in LTS whereas platelet derived
      growth factor receptor (PDGFR) signalling was more abundant in STS. Expression of
      TIE2/Tek, a receptor for tyrosine kinases involved in angiogenesis, was
      differentially regulated via PDGFR and thus is more important in STS.
      Antiapoptosis was upregulated in STS by signal transducer and activator of
      transcription 1 (STAT1)-survivin and related molecules, but not in LTS. Our study
      provides novel insights into the regulatory mechanisms of signalling pathways in
      MPM, which differentially promote tumour growth in LTS and STS. CONCLUSION: We
      have demonstrated that small scale proteomics can be carried out by powerful
      linkage of TMA, immunohistochemistry and statistical methods to identify proteins
      which might be relevant targets for therapeutic intervention.

PMID- 18086753
TI  - Ethical, legal, and policy issues: dominating the biospecimen discussion.

PMID- 18086754
TI  - Ovarian cancer and menopausal hormone therapy: more data and new questions.

PMID- 18086755
TI  - Adiposity and age are statistically related to enhanced RASSF1A tumor suppressor
      gene promoter methylation in normal autopsy kidney tissue.
AB  - Age, adiposity, and smoking are risk factors for the development of renal cell
      carcinoma. Hypermethylation of the RAS association domain family 1A gene
      (RASSF1A) promoter belongs to the most frequently detected epigenetic alterations
      in human cancers including renal cell carcinoma. RASSF1A is functionally involved
      in cell cycle control in normal cells and depletion promotes a number of cellular
      changes increasing the risk for neoplastic growth. We investigated the hypothesis
      that age, modulated by the factors adiposity and anthracosis as a surrogate for
      smoking, is a predictor of RASSF1A promoter methylation in normal kidney tissue.
      Using a cross-sectional study design, we quantitatively analyzed RASSF1A
      methylation in 78 normal autopsy kidney tissues by quantitative combined
      bisulfite and restriction analysis and bisulfite sequencing, and statistically
      evaluated the degree of relative methylation for a relationship with the
      predictor age and study factors adiposity and state of anthracosis. Statistical
      analysis showed that age (regression analysis; P < 0.001), adiposity (univariate
      analysis; P = 0.016), and state of anthracosis (t test; P = 0.005) are each
      significantly associated with an increase of RASSF1A promoter methylation in
      normal kidney tissue. However, only age (P = 0.008) and adiposity (P = 0.008)
      were identified as independent predictors of RASSF1A promoter methylation using
      covariance analysis. This study provides statistical evidence that the common
      cancer risk factors age and adiposity enhance RASSF1A promoter methylation in
      nonmalignant kidney tissue.

PMID- 18086756
TI  - Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000
      events.
AB  - BACKGROUND: Colorectal cancer is the second most common cause of death and
      illness in developed countries. Previous reviews have suggested that obesity may
      be associated with 30% to 60% greater risk of colorectal cancer, but little
      consideration was given to the possible effect of publication bias on the
      reported association. METHODS: Relevant studies were identified through EMBASE
      and MEDLINE. Studies were included if they had published quantitative estimates
      of the association between general obesity [defined here as body mass index (BMI)
      > or = 30 kg/m(2)] and central obesity (measured using waist circumference) and
      colorectal cancer. Random-effects meta-analyses were done, involving 70,000 cases
      of incident colorectal cancer from 31 studies, of which 23 were cohort studies
      and 8 were case-control studies. RESULTS: After pooling and correcting for
      publication bias, the estimated relative risk of colorectal cancer was 1.19 [95%
      confidence interval (95% CI), 1.11-1.29], comparing obese (BMI > or = 30 kg/m(2))
      with normal weight (BMI <25 kg/m(2)) people; and 1.45 (95% CI, 1.31-1.61),
      comparing those with the highest, to the lowest, level of central obesity. After
      correcting for publication bias, the risk of colorectal cancer was 1.41 (95% CI,
      1.30-1.54) in men compared with 1.08 (95% CI, 0.98-1.18) for women
      (P(heterogeneity) <0.001). There was evidence of a dose-response relationship
      between BMI and colorectal cancer: for a 2 kg/m(2) increase in BMI, the risk of
      colorectal cancer increased by 7% (4-10%). For a 2-cm increase in waist
      circumference, the risk increased by 4% (2-5%). CONCLUSIONS: Obesity has a direct
      and independent relationship with colorectal cancer, although the strength of the
      association with general obesity is smaller than previously reported.

PMID- 18086757
TI  - Menopausal hormone therapy and risk of epithelial ovarian cancer.
AB  - Substantial increase in the use of menopausal hormone therapy (HT) throughout the
      1990s, followed by widespread discontinuation after the 2002 publication of the
      Women's Health Initiative findings, has resulted in large numbers of former HT
      users among U.S. women. However, few studies have examined whether ovarian cancer
      risk varies according to recency and duration of specific HT regimens. We
      assessed risk of epithelial ovarian cancer among users of unopposed estrogen (ET)
      and combined estrogen/progestogen (EPT). In a population-based study in
      Washington state, 812 women with ovarian cancer diagnosed in 2002 to 2005 and
      1,313 controls were interviewed in person about the use of HT and other
      characteristics. Women who used a single form of therapy (ET or EPT) were
      compared with women who never used HT using logistic regression to calculate odds
      ratios (OR) and 95% confidence intervals (95% CIs). Risk was increased among
      current or recent (within the last 3 years) users of ET with > or = 5 years of
      use (ORs, 95% CIs: 1.6, 1.1-2.5 and 1.8, 0.8-3.7, respectively). Little increase
      in risk was noted among long-term ET users who discontinued use in the more
      distant past (OR, 1.2; 95% CI, 0.6-2.6). No increase in risk was noted among
      women who used only EPT, regardless of duration. Compared with women who never
      used HT, current users of EPT had an OR of 1.1 (95% CI, 0.8-1.5), and risk
      declined with increasing time since stopping; the OR was 0.7 (95% CI, 0.4-1.0)
      among women who had discontinued EPT within the last 3 years and 0.5 (95% CI, 0.3
      0.7) among women who stopped at an earlier point. Long-term ET may be associated
      with an increased ovarian cancer risk that wanes after use ceases. We did not
      observe an increased risk with EPT, and with increasing time after stopping, a
      reduction in risk became increasingly evident. The progestogen component of HT
      may confer a risk reduction that is masked by an opposing effect of estrogen
      until, among former users, estrogenic influences have diminished. These findings,
      if replicated, may have implications both for public health and development of
      chemoprevention strategies.

PMID- 18086759
TI  - Vitamin D receptor gene polymorphisms and epithelial ovarian cancer risk.
AB  - Epidemiologic and laboratory studies support a role for the vitamin D endocrine
      system in ovarian carcinogenesis. The association of ovarian cancer risk with
      polymorphisms in the vitamin D receptor (VDR) gene, including rs10735810 (FokI),
      rs11568820 (Cdx-2), rs1544410 (BsmI), rs7975232 (ApaI), rs731236 (TaqI), and BsmI
      ApaI-TaqI combined genotypes, was examined among 313 women with epithelial
      ovarian carcinoma and 574 controls. Odds ratios (OR) and 95% confidence intervals
      (95% CI) were estimated using unconditional logistic regression. The associations
      of VDR polymorphisms with risk were generally inconsistent across ethnic groups.
      Among Caucasian women (72 cases, 148 controls), heterozygous and homozygous ApaI
      A allele carriers were at increased ovarian carcinoma risk compared with
      homozygous carriers of the ApaI a allele (OR 2.8, 95% CI 1.2-7.0 and OR 3.4, 95%
      CI 1.3-9.1; P(trend) = 0.02). Caucasian heterozygous carriers of FokI f allele
      were also at increased risk of ovarian carcinoma compared with homozygous
      carriers of the common allele (OR 2.5, 95% CI 1.3-4.8; P(trend) = 0.04). Among
      Japanese women (94 cases, 173 controls), ovarian cancer risk was significantly
      decreased (OR 0.5, 95% CI 0.3-0.9) among Cdx-2 A allele heterozygotes compared
      with homozygote G allele carriers (P(trend) = 0.03). Compared with the bbaaTT
      BsmI-ApaI-TaqI genotype, bbaATT and BBAAtt genotypes were associated with
      increased ovarian cancer risk in Caucasian women (OR 4.2, 95% CI 1.3-13.1 and OR
      5.2, 95% CI 1.6-17.5), but not in Japanese women (OR 1.1, 95% CI 0.6-1.9 and OR
      2.3, 95% CI:0.4-12.3). This investigation provides some evidence that
      polymorphisms in the VDR gene might influence ovarian cancer susceptibility.

PMID- 18086758
TI  - Association between single-nucleotide polymorphisms in hormone metabolism and DNA
      repair genes and epithelial ovarian cancer: results from two Australian studies
      and an additional validation set.
AB  - Although some high-risk ovarian cancer genes have been identified, it is likely
      that common low penetrance alleles exist that confer some increase in ovarian
      cancer risk. We have genotyped nine putative functional single-nucleotide
      polymorphisms (SNP) in genes involved in steroid hormone synthesis (SRD5A2,
      CYP19A1, HSB17B1, and HSD17B4) and DNA repair (XRCC2, XRCC3, BRCA2, and RAD52)
      using two Australian ovarian cancer case-control studies, comprising a total of
      1,466 cases and 1,821 controls of Caucasian origin. Genotype frequencies in cases
      and controls were compared using logistic regression. The only SNP we found to be
      associated with ovarian cancer risk in both of these two studies was SRD5A2 V89L
      (rs523349), which showed a significant trend of increasing risk per rare allele
      (P = 0.00002). We then genotyped another SNP in this gene (rs632148; r(2) = 0.945
      with V89L) in an attempt to validate this finding in an independent set of 1,479
      cases and 2,452 controls from United Kingdom, United States, and Denmark. There
      was no association between rs632148 and ovarian cancer risk in the validation
      samples, and overall, there was no significant heterogeneity between the results
      of the five studies. Further analyses of SNPs in this gene are therefore
      warranted to determine whether SRD5A2 plays a role in ovarian cancer
      predisposition.

PMID- 18086760
TI  - Six-month follow-up of patient-rated outcomes in a randomized controlled trial of
      exercise training during breast cancer chemotherapy.
AB  - BACKGROUND: Few exercise trials in cancer patients have reported longer-term
      follow-up. Here, we report a 6-month follow-up of exercise behavior and patient
      rated outcomes from an exercise trial in breast cancer patients. METHODS: Breast
      cancer patients initiating adjuvant chemotherapy (n = 242) were randomly assigned
      to usual care (n = 82), resistance exercise training (RET; n = 82), or aerobic
      exercise training (AET; n = 78) for the duration of their chemotherapy. At 6
      month follow-up, participants were mailed a questionnaire that assessed quality
      of life, self-esteem, fatigue, anxiety, depression, and exercise behavior.
      RESULTS: Two hundred one (83.1%) participants provided 6-month follow-up data.
      Adjusted linear mixed-model analyses showed that, at 6-month follow-up, the RET
      group reported higher self-esteem [adjusted mean difference, 1.6; 95% confidence
      interval (95% CI), 0.1-3.2; P = 0.032] and the AET group reported lower anxiety
      (adjusted mean difference, -4.7; 95% CI, -0.0 to -9.3; P = 0.049) compared with
      the usual care group. Moreover, compared with participants reporting no regular
      exercise during the follow-up period, those reporting regular aerobic and
      resistance exercise also reported better patient-rated outcomes, including
      quality of life (adjusted mean difference, 9.5; 95% CI, 1.2-17.8; P = 0.025).
      CONCLUSIONS: Improvements in self-esteem observed with RET during breast cancer
      chemotherapy were maintained at 6-month follow-up whereas reductions in anxiety
      not observed with AET during breast cancer chemotherapy emerged at 6-month follow
      up. Moreover, adopting a combined aerobic and resistance exercise program after
      breast cancer chemotherapy was associated with further improvements in patient
      rated outcomes. Exercise training during breast cancer chemotherapy may result in
      some longer-term and late effects for selected patient-rated outcomes.

PMID- 18086761
TI  - Plasma isoflavones and fibrocystic breast conditions and breast cancer among
      women in Shanghai, China.
AB  - BACKGROUND: Proliferative benign breast conditions are associated with elevated
      risk of breast cancer, whereas nonproliferative conditions are not strongly
      associated with risk. Factors acting before onset of hyperplasia might be
      associated with both benign conditions and breast cancer, whereas those on the
      proliferative disease-to-cancer pathway would be associated only with cancer. Soy
      isoflavone exposure may influence breast cancer risk, but little is known of its
      association with benign conditions. MATERIALS AND METHODS: We examined possible
      relationships between plasma genistein and daidzein concentrations and risk of
      breast disease in women, in a breast self-examination trial in Shanghai, China,
      diagnosed with breast cancer (n = 196) or a benign breast condition (n = 304),
      and 1,002 age-matched controls with no known breast disease. Benign conditions
      were classified as nonproliferative (n = 131) or proliferative with or without
      atypia (n = 173). RESULTS: Isoflavone concentrations were inversely associated
      with risk of nonproliferative and proliferative benign fibrocystic conditions, as
      well as with breast cancer, both with and without concomitant proliferative
      changes in ipsilateral noncancerous mammary epithelium (P(trend) < 0.01 for all
      comparisons with controls). Women in the highest quartile of plasma genistein
      (>76.95 ng/mL) were less likely to have breast cancer (odds ratio, 0.26; 95%
      confidence interval, 0.13-0.50) or benign conditions (odds ratio, 0.40; 95%
      confidence interval, 0.23-0.70) compared with women in the lowest quartile (<9.42
      ng/mL). Observed risks for breast cancer with and without surrounding
      proliferative changes were not different, respectively, from observed risks for
      benign proliferative and nonproliferative conditions alone. CONCLUSION:
      Isoflavone exposure was inversely associated with fibrocystic breast conditions
      and breast cancer, and the results suggest that effects on cancer risk occur
      early in carcinogenesis.

PMID- 18086762
TI  - Association between breast density and subsequent breast cancer following
      treatment for ductal carcinoma in situ.
AB  - BACKGROUND: Risk of invasive cancer following treatment for ductal carcinoma in
      situ (DCIS) is associated with both treatment- and tumor-related factors.
      However, it is unknown whether stromal factors such as breast density may also
      influence subsequent invasive breast events. We investigated whether breast
      density is an independent predictor of subsequent breast events among women
      treated for DCIS. POPULATION: A prospective cohort study of 3,274 women ages 30
      to 93 in the Breast Cancer Surveillance Consortium treated with lumpectomy for
      DCIS between 1993 and 2005. All subjects had an American College of Radiology
      Breast Imaging Reporting and Data System (BI-RADS) breast density measure
      recorded prior to diagnosis. METHODS: Ipsilateral and contralateral breast cancer
      following lumpectomy for DCIS were ascertained through state tumor registries,
      regional Surveillance Epidemiology and End Results program or pathology
      databases. A Cox proportional hazard model was used to compare adjusted risk of
      breast cancer among women with high (BI-RADS 3 or 4) versus low (BI-RADS 1 or 2)
      breast density. RESULTS: During a median follow-up period of 39 months (0-132
      months), 133 women developed invasive breast cancer. After adjusting for age and
      radiation treatment, high breast density was associated with increased hazard for
      contralateral (hazard ratio, 3.1; 95% confidence interval, 1.6-6.1) but not
      ipsilateral (hazard ratio, 1.0; 95% confidence interval, 0.6-1.6) invasive breast
      events. CONCLUSION: High breast density is associated with contralateral, but not
      ipsilateral, invasive breast cancer following lumpectomy for DCIS. Thus, women
      with DCIS and high breast density may especially benefit from antiestrogenic
      therapy to reduce the risk of contralateral invasive disease.

PMID- 18086763
TI  - Results of a randomized trial to increase mammogram usage among Samoan women.
AB  - BACKGROUND: There are no effective breast cancer education programs targeting
      Samoan women. We tested the effectiveness of a theory-guided, culturally
      appropriate breast cancer education program (the intervention) designed to
      increase mammography use among Samoan women. METHODS: This community-based
      participatory cluster-randomized controlled intervention trial used a parallel
      two-group design. The sample consisted of 776 women aged 42 and older who had not
      had a mammogram in the preceding 2 years. The primary outcome was self-reported
      mammogram use between pretest and posttest. RESULTS: Overall, there was no
      statistically significant intervention effect, although the odds of self-reported
      mammogram use were higher in the intervention than the control group (odds ratio
      (OR), 1.26; 95% confidence interval (95% CI), 0.74, 2.14; P = 0.39). Exploratory
      subgroup analyses found that the intervention was effective only among women who
      were aware of mammograms but had never previously obtained one (OR, 1.99; 95% CI,
      1.03, 3.85; P = 0.04). Low need for social support and lack of endorsement of
      culture-specific beliefs about breast cancer were associated with mammogram use
      in this group. In women unaware of mammography at pretest, high perceived
      susceptibility to breast cancer and endorsement of culture-specific beliefs were
      associated with mammogram use. For women who had previously obtained a mammogram,
      lower self-efficacy was associated with mammogram use. Intervention compared with
      control group women had significantly higher levels of knowledge of risk factors
      and lower endorsement of culture-specific beliefs at posttest. CONCLUSIONS:
      Results suggest that a multifaceted education intervention may improve mammogram
      usage for certain subgroups of Samoan women.

PMID- 18086764
TI  - Strategies and cost of recruitment of middle-aged and older unmarried women in a
      cancer screening study.
AB  - OBJECTIVES: We compared strategies and costs associated with recruiting unmarried
      middle-aged and older women who partner with women (WPW) and women who partner
      with men (WPM) into an observational study about experiences with cancer
      screening. METHODS: We used targeted and respondent-driven sampling methods to
      recruit potential participants. Comparable recruitment strategies were used for
      WPW and WPM. RESULTS: During 25 months (June 1, 2003, through June 30, 2005), 773
      women were screened for study eligibility; 630 were enrolled (213 WPW, 417 WPM).
      Average staff time spent for recruitment was 100 min per participant. There were
      no differences by partner gender in average recruitment time (WPW, 90 min; WPM,
      100 min). Print media was the most efficient recruitment mode (time per
      participant: 10 min for WPW, 15 min for WPM). Recruitment costs differed by
      partner gender ($140 for WPW, $110 for WPM). Costs associated with print media
      were $10 per WPW and $20 per WPM. Recruitment through community events had higher
      costs ($490 per WPW, $275 per WPM) but yielded more women with less education and
      lower incomes, who identified as a racial or ethnic minority, and self-reported a
      disability. Compared with WPM, WPW had more education and higher incomes, but
      were less likely to identify as a racial minority and self-report a disability.
      CONCLUSIONS: There was a trade-off between cost and sample diversity for the
      different recruitment methods. The per-person costs were lowest for print media,
      but recruitment through community events ensured a more diverse representation of
      unmarried heterosexual and sexual minority women.

PMID- 18086765
TI  - Dicarbonyl/L-xylulose reductase: a potential biomarker identified by laser
      capture microdissection-micro serial analysis of gene expression of human
      prostate adenocarcinoma.
AB  - To identify genes involved in prostate carcinogenesis, we used laser-capture
      microdissection-micro serial analysis of gene expression to construct libraries
      of paired cancer and normal cells from human tissue samples. After computational
      comparison of the two libraries, we identified dicarbonyl/l-xylulose reductase
      (DCXR), an enzyme that catalyzes alpha-dicarbonyl and l-xylulose, as being
      significantly up-regulated in prostate cancer cells. The specificity of DCXR up
      regulation for prostate cancer tissues was confirmed by quantitative real-time
      reverse transcriptase-PCR, virtual Northern blot, and Western blot analyses.
      Furthermore, DCXR expression at the protein level was assessed using fresh-frozen
      tissues and a tissue microarray consisting of 46 cases of organ-confined early
      stage prostate cancer and 29 cases of chemohormonally treated prostate cancer. In
      most normal prostate epithelial cells, DCXR was expressed at low levels and was
      localized predominantly in the cytoplasmic membrane. In contrast, in virtually
      all grades of early-stage prostate cancer and in all chemohormonally treated
      cases, DCXR was strikingly overexpressed and was localized predominantly in the
      cytoplasm and nucleus. In all samples, the stromal cells were completely devoid
      of DCXR expression. Based on these findings, we suggest that DCXR overexpression
      has the potential to be an additional useful biomarker for prostate cancer.

PMID- 18086766
TI  - Dairy products, calcium intake, and risk of prostate cancer in the prostate,
      lung, colorectal, and ovarian cancer screening trial.
AB  - Higher intakes of calcium and dairy products, a major source of dietary calcium,
      are reported to increase the risk of prostate cancer, potentially due to
      reductions in circulating vitamin D with increasing calcium intake. We
      prospectively examined the association of dairy product and calcium intake with
      prostate cancer risk in 29,509 men, including 1,910 cases, in the Prostate, Lung,
      Colorectal, and Ovarian Cancer Screening Trial. We also evaluated the relation of
      calcium intake with serum 25-hydroxy-vitamin D [25(OH)D] and 1,25-dihydroxy
      vitamin D [1,25(OH)(2)D], in a Prostate, Lung, Colorectal, and Ovarian Trial
      substudy (n = 275). Dietary intake was assessed using a food frequency
      questionnaire. Baseline serum 1,25(OH)(2)D was determined by RIA. Greater intake
      of dairy products, particularly low-fat dairy products, was weakly associated
      with increased risk of prostate cancer [relative risk (RR), 1.12; 95% confidence
      intervals (CI), 0.97-1.30; P trend = 0.06 for >2.75 versus < or = 0.98 servings
      of total dairy/day; 1.23 (1.07-1.41) for low-fat dairy]. Greater dietary calcium
      intake was associated with increased risk of prostate cancer (RR, 1.34; 95% CI,
      0.93-1.94; P trend = 0.02 for >2,000 versus <1,000 mg/day), but greater
      supplementary calcium intake was not associated with the risk. Associations of
      dairy product and dietary calcium intake were evident for nonaggressive disease
      (RR, 1.20; 95% CI, 0.99-1.46; P trend = 0.01 for dairy products; 1.64, 1.04-2.57;
      P trend = 0.002 for dietary calcium), but not aggressive disease (RR, 1.02; 95%
      CI, 0.81-1.28 for dairy products; 0.94, 0.49-1.80 for dietary calcium). Calcium
      intake was not associated with serum 25-hydroxy-vitamin D and 1,25(OH)(2)D
      concentration. In this large prospective study in a prostate cancer screening
      trial, greater dietary intake of calcium and dairy products, particularly low-fat
      types, may be modestly associated with increased risks for nonaggressive prostate
      cancer, but was unrelated to aggressive disease. Furthermore, we found no
      relationship between calcium intake and circulating vitamin D.

PMID- 18086767
TI  - Serum pepsinogen levels, Helicobacter pylori CagA Status, and cytokine gene
      polymorphisms associated with gastric premalignant lesions in Costa Rica.
AB  - The detection of gastric premalignant lesions, atrophic gastritis, corpus
      atrophic gastritis, and intestinal metaplasia, using several potential markers
      was examined in Costa Rica. Depending on the lesion investigated, from a total of
      223 dyspeptic patients, 58 (26.0%), 31 (13.9%), or 23 (10.3%) were histologically
      diagnosed with atrophic gastritis, corpus atrophic gastritis, or intestinal
      metaplasia, respectively. Sera were used for the measurement of pepsinogen (PG)
      and Helicobacter pylori CagA antibody (CagA-ab) levels by ELISA, and human
      genomic DNAs were used for the genotyping of interleukin (IL)-1beta (-511 and
      +3954), IL-10 (-1082 and -592), and IL-1RN intron 2 by PCR and RFLP. Multivariate
      analysis was done adjusting for sex, age, and H. pylori seropositivity. Low PG
      levels (L-PG; PG I < or = 70 microg/L + PG I/II < or = 3), very low PG levels (VL
      PG; PG I < or = 30 microg/L + PG I/II < or = 2), and CagA-ab were individually
      associated with all premalignant lesions whereas IL-1beta +3954T-carrier and IL
      1RN homozygous 2 allele were associated with intestinal metaplasia. VL-PG, for
      corpus atrophic gastritis detection, was the single marker with the highest
      combination of test characteristics, sensitivity (77.4%), specificity (80.7%),
      positive predictive value (39.3%), negative predictive value (95.7%), and
      seropositivity rate (27.4%), expected to improve after periodic measurements.
      Combined examinations of VL-PG and CagA-ab improved the specificity (92.7%) and
      positive predictive value (62.2%), with similar sensitivity (74.2%) and negative
      predictive value (95.7%). In conclusion, corpus atrophic gastritis detection with
      periodic measurements of serum PG, alone or in combination with CagA-ab status,
      to identify high gastric cancer risk, seems to be the method best suited for mass
      screening in Costa Rica.

PMID- 18086768
TI  - Decreasing trend of esophageal adenocarcinoma in Hong Kong.
AB  - BACKGROUND: The incidence of esophageal adenocarcinoma was increasing in the
      Western Europe and United States, but not in East Asian countries. Population
      based study on the trend of esophageal adenocarcinoma in Hong Kong was not
      available. MATERIALS AND METHODS: Population-based data of Hong Kong Cancer
      Registry from 1984 to 2003 were used. Cases were grouped into four 5-year
      periods. Average age standardized rate (WSR) of each period was calculated by
      averaging the WSR of the 5 years in each period, basing on the world standard
      population, with adjustment made for cases with missing histology. RESULTS:
      10,751 new cases of esophageal neoplasm were studied (8,637 males and 2,114
      females). Esophageal adenocarcinoma declined among both males and females, with
      the total number decreased from 224 in 1984 to 1988 to 131 in 1998 to 2003. WSR
      decreased from 1.10 of 100,000 in 1984 to 1988 to 0.34 of 100,000 in 1998 to
      2003. The decline was faster than that for esophageal squamous cell carcinoma so
      that the relative ratio of esophageal adenocarcinoma decreased from 11.7% in 1984
      to 1988 to 6.4% in 1998 to 2003. CONCLUSIONS: The incidence of esophageal
      adenocarcinoma and ratio of esophageal adenocarcinoma versus esophageal squamous
      cell carcinoma decreased in Hong Kong.

PMID- 18086769
TI  - A longitudinal Swedish study on screening for squamous cell carcinoma and
      adenocarcinoma: evidence of effectiveness and overtreatment.
AB  - BACKGROUND: Organized Papanicolaou (Pap) screening has markedly reduced the
      incidence of cervical squamous cell carcinoma (SCC). However, the potential for
      overtreatment of precursor lesions is quite high for SCC, and the effectiveness
      of Pap screening for prevention of cervical adenocarcinoma is questionable.
      METHODS: Using the nationwide, virtually complete Swedish Cancer Register, we
      analyzed standardized incidence rates for SCC in situ (CIS), SCC, adenocarcinoma
      in situ (AIS) and adenocarcinoma, between 1968 and 2002. For each county, we
      calculated Spearman correlations between incidence of in situ lesions and
      incidence of invasive cancer, 5, 10, and 15 years later. We also used generalized
      estimating equation (GEE) models to compare adjusted estimates for associations
      between in situ incidences and invasive carcinomas over counties. RESULTS: The
      overall decrease in SCC incidence in Sweden following the introduction of
      cervical screening confirms the beneficial nature of cervical screening on SCC
      incidence over the last 30 years. A similar benefit was not apparent for
      adenocarcinoma. GEE estimates for the relative change in SCC for an increase of
      100 CIS cases per 100,000 women-years were 1.05 for the 5-year and 1.02 for the
      10-year lag periods. For adenocarcinoma and AIS, similar analyses gave
      corresponding estimates of 1.17 for the 5-year and 1.08 for the 10-year lag
      periods. The lack of an inverse correlation suggests that increased reported
      incidence of CIS in certain counties did not forecast a reduction in SCC for
      those counties. CONCLUSION: Our data confirm the effectiveness of Pap smear
      screening in reducing the incidence of SCC, but suggest no clear benefit on
      adenocarcinoma. Our data also suggest that relaxed histopathologic criteria for
      diagnosis of cervical CIS may increase its recorded incidence with no measurable
      benefit in the reduction of invasive cancer.

PMID- 18086770
TI  - Leukocyte telomere length predicts cancer risk in Barrett's esophagus.
AB  - PURPOSE: Leukocyte telomere length has gained attention as a marker of oxidative
      damage and age-related diseases, including cancer. We hypothesize that leukocyte
      telomere length might be able to predict future risk of cancer and examined this
      in a cohort of patients with Barrett's esophagus, who are at increased risk of
      esophageal adenocarcinoma and thus were enrolled in a long-term cancer
      surveillance program. PATIENTS AND METHODS: In this prospective study, telomere
      length was measured by quantitative PCR in baseline blood samples in a cohort of
      300 patients with Barrett's esophagus followed for a mean of 5.8 years. Leukocyte
      telomere length hazard ratios (HR) for risk of esophageal adenocarcinoma were
      calculated using multivariate Cox models. RESULTS: Shorter telomeres were
      associated with increased esophageal adenocarcinoma risk (age-adjusted HR between
      top and bottom quartiles of telomere length, 3.45; 95% confidence interval, 1.35
      8.78; P = 0.009). This association was still significant when individually or
      simultaneously adjusted for age, gender, nonsteroidal anti-inflammatory drug
      (NSAID) use, cigarette smoking, and waist-to-hip ratio (HR, 4.18; 95% confidence
      interval, 1.60-10.94; P = 0.004). The relationship between telomere length and
      cancer risk was particularly strong among NSAID nonusers, ever smokers, and
      patients with low waist-to-hip ratio. CONCLUSION: Leukocyte telomere length
      predicts risk of esophageal adenocarcinoma in patients with Barrett's esophagus
      independently of smoking, obesity, and NSAID use. These results show the ability
      of leukocyte telomere length to predict the risk of future cancer and suggest
      that it might also have predictive value in other cancers arising in a setting of
      chronic inflammation.

PMID- 18086771
TI  - Distinctive heavy metal composition of pancreatic juice in patients with
      pancreatic carcinoma.
AB  - Epidemiologic studies have shown the health risks of exposure to cigarette smoke
      and air pollution, with heavy metal composition implicated as contributing to
      both. Environmental exposure to cigarette smoke has been epidemiologically
      associated with pancreatic cancer, but the pathophysiologic basis for this is not
      yet clear. In the current work, we have used inductively coupled plasma mass
      spectrometry to quantify the metal composition of pancreatic juice collected in
      response to secretin stimulation in successive patients evaluated for abdominal
      pain (35 with pancreatic cancer, 30 with chronic pancreatitis, and 35 with normal
      pancreas). Indeed, metal composition of pancreatic juice was distinctive in
      patients with pancreatic cancer relative to those without such a cancer. The
      metal concentrations that were found to have the strongest association with
      pancreatic cancer were chromium, selenium, and molybdenum, with 1 SD increases in
      the concentrations of each associated with substantial increases in the odds of
      having pancreatic cancer relative to those in patients with normal pancreas
      (210%, 160%, and 76%, respectively). Of note, elevations in concentrations of
      chromium and selenium did not correlate in individuals, whereas those having a 1
      SD increase in the sum of the concentrations of these two metals in their
      pancreatic juice had a 480% increase in the odds of having pancreatic cancer.
      Elevations of nickel and zinc correlated with elevated chromium in individuals,
      with each of these metals known to be present in cigarette smoke, whereas other
      recognized metal components of cigarette smoke were not elevated. An
      understanding of why these metals are elevated in pancreatic juice and what
      effects they might have on pancreatic cells may have important implications for
      the diagnosis, treatment, and even prevention of pancreatic cancer.

PMID- 18086772
TI  - Meat and meat-mutagen intake and pancreatic cancer risk in the NIH-AARP cohort.
AB  - Meat intake, particularly red meat, has been positively associated with
      pancreatic cancer in some epidemiologic studies. Detailed meat-cooking methods
      and related mutagens formed in meat cooked at high temperatures have not been
      evaluated prospectively as risk factors for this malignancy. We investigated the
      association between meat, meat-cooking methods, meat-mutagen intake, and exocrine
      pancreatic cancer in the NIH-American Association of Retired Persons (NIH-AARP)
      Diet and Health Study cohort of 537,302 individuals, aged 50 to 71 years, with
      complete baseline dietary data (1995-1996) ascertained from a food frequency
      questionnaire. A meat-cooking module was completed by 332,913 individuals 6
      months after baseline. During 5 years of follow-up, 836 incident pancreatic
      cancer cases (555 men, 281 women) were identified. Four hundred and fifty-nine
      cases had complete meat module data. We used Cox proportional hazard models to
      calculate hazard ratios (HR) and 95% confidence intervals (CI). Total, red, and
      high-temperature cooked meat intake was positively associated with pancreatic
      cancer among men (fifth versus first quintile: HR, 1.41, 95% CI, 1.08-1.83, P
      trend = 0.001; HR, 1.42, 95% CI, 1.05-1.91, P trend = 0.01; and HR, 1.52, 95% CI,
      1.12-2.06, P trend = 0.005, respectively), but not women. Men showed significant
      50% increased risks for the highest tertile of grilled/barbecued and broiled meat
      and significant doubling of risk for the highest quintile of overall meat
      mutagenic activity (P trends < 0.01). The fifth quintile of the heterocyclic
      amine, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline intake showed a
      significant 29% (P trend = 0.006) increased risk in men and women combined. These
      findings support the hypothesis that meat intake, particularly meat cooked at
      high temperatures and associated mutagens, may play a role in pancreatic cancer
      development.

PMID- 18086773
TI  - Cytokinesis-block micronucleus cytome assays for the determination of
      genotoxicity and cytotoxicity of cecal water in rats and fecal water in humans.
AB  - We tested the cytokinesis-block micronucleus cytome assay using the WIL2-NS human
      B lymphoblastoid cell line as a biomarker of genotoxicity and cytotoxicity of
      cecal water from rats and fecal water from humans. Cecal water was assessed in
      rats fed either a diet rich in fat, low in calcium and fiber, and barbecued red
      meat as the protein source (high colorectal cancer risk diet) or a diet high in
      fiber and calcium, low in fat, and casein as the protein source (low colorectal
      cancer risk diet) for 2 weeks. There was a significant 7.6-, 1.8-, and 4.0-fold
      increase in binucleated (BN) cells with micronuclei (Mn-BN), BN cells with
      nucleoplasmic bridges (Npb-BN), and necrotic cells (P < 0.001) with 1-h
      incubation with a 10% dilution of the cecal water isolated from rats fed the high
      colorectal cancer risk diet compared with rats fed the low colorectal cancer risk
      diet. In humans, fecal water samples collected from feces of free-living
      volunteers showed that 24-h exposure to 1% dilution of fecal water produced a
      significant 2.6-, 6.5-, 7.5-, and 2.2-fold increase in Mn-BN, Npb-BN, BN cells
      with nuclear buds, and necrotic cells compared with controls (P < 0.05). The
      coefficients of variations for interindividual differences for Mn-BN, Npb-BN, BN
      cells with nuclear buds, and necrosis biomarkers were greater than corresponding
      coefficients of variations for intraindividual variation. These results indicate
      that the cytokinesis-block micronucleus cytome assay can be used successfully to
      determine the interindividual variation in genotoxicity and cytotoxicity of cecal
      or fecal water and to identify dietary patterns that are likely to increase
      carcinogenic events in the colon.

PMID- 18086774
TI  - Adduction of human p53 gene by fecal water: an in vitro biomarker of mutagenesis
      in the human large bowel.
AB  - A polymerase arrest assay was designed to determine sites of adduction in the
      human p53 gene induced by incubation with fecal water. Significant formation of
      adducts was observed on p53 DNA after a 2-h incubation in fecal water from 10 of
      17 samples studied. Large sample-to-sample variation was observed. The major
      sites of polymerase termination occurred at nucleotides 3' to guanine residues.
      Adduct sites coincided with colorectal cancer p53 mutation "hotspots,"
      highlighting the potential carcinogenicity of fecal material.

PMID- 18086775
TI  - Highly methylated genes in colorectal neoplasia: implications for screening.
AB  - Discriminant markers are required for accurate cancer screening. We evaluated
      genes frequently methylated in colorectal neoplasia to identify the most
      discriminant ones. Four genes specifically methylated in colorectal cancer [bone
      morphogenetic protein 3 (BMP3), EYA2, aristaless-like homeobox-4 (ALX4), and
      vimentin] were selected from 41 candidate genes and evaluated on 74 cancers, 62
      adenomas, and 70 normal epithelia. Methylation status was analyzed qualitatively
      and quantitatively and confirmed by bisulfite genomic sequencing. Effect of
      methylation on gene expression was evaluated in five colon cancer cell lines. K
      ras and BRAF mutations were detected by sequencing. Methylation of BMP3, EYA2,
      ALX4, or vimentin was detected respectively in 66%, 66%, 68%, and 72% of cancers;
      74%, 48%, 89%, and 84% of adenomas; and 7%, 5%, 11%, and 11% of normal epithelia
      (P < 0.01, cancer or adenoma versus normal). Based on area under the curve
      analyses, discrimination was not significantly improved by combining markers.
      Comethylation was frequent (two genes or more in 72% of cancers and 84% of
      adenomas), associated with proximal neoplasm site (P < 0.001), and linked with
      both BRAF and K-ras mutations (P < 0.01). Cell line experiments supported
      silencing of expression by methylation in all four study genes. This study shows
      BMP3, EYA2, ALX4, and vimentin genes are methylated in most colorectal neoplasms
      but rarely in normal epithelia. Comethylation of these genes is common, and
      pursuit of complementary markers for methylation-negative neoplasms is a rational
      strategy to optimize screening sensitivity.

PMID- 18086776
TI  - Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma
      risk.
AB  - Obesity has been shown to be associated with an increased risk of both colorectal
      cancer and adenomatous polyps. One mechanism underlying this relationship may
      involve the growth-promoting effects of the circulating hormones associated with
      obesity, such as leptin. We conducted a gastroenterology clinic-based, case
      control study to evaluate the relationship between circulating leptin
      concentrations and colorectal adenoma risk; in addition, we evaluated the
      relationship between leptin receptor polymorphisms and adenoma risk. Individuals
      with adenomas (n = 157) and colonoscopy-negative controls (n = 191), who had a
      clinically indicated colonoscopy, were recruited from a large health maintenance
      organization in the Seattle metropolitan area from 1999 to 2003. Odds ratios and
      95% confidence intervals were obtained using logistic regression, adjusting for
      age at diagnosis, body mass index, family history of colorectal cancer, smoking
      history, nonsteroidal anti-inflammatory drug use, physical activity, and, among
      women, menopausal status and postmenopausal hormone use. Among men, those in the
      highest tertile of leptin concentrations had a 3.3-fold (95% confidence interval,
      1.2-8.7) increased adenoma risk compared with those in the lowest tertile (P
      trend = 0.01). There were no associations between leptin concentrations and
      adenoma risk in women. There were no associations of leptin receptor genotypes or
      haplotypes and adenoma risk. The results of this study suggest that, in men,
      leptin may be associated with risk of colorectal adenomas.

PMID- 18086777
TI  - Karyometry of the colonic mucosa.
AB  - OBJECTIVE: The study summarizes results of karyometric measurements in epithelial
      cells of the colorectal mucosa to document evidence of a field effect of
      preneoplastic development among patients with colorectal adenocarcinoma or
      adenoma. METHODS: Karyometric analyses were done on high-resolution images of
      histologic sections from 48 patients with colorectal adenocarcinomas and 44
      patients with adenomas and on images from matching normal-appearing mucosa
      directly adjacent to such lesions, at a 1-cm and 10-cm distance from the lesions
      or from the rectal mucosa of adenoma patients, as well as from 24 healthy normal
      controls with no family history of colonic disease. RESULTS: The nuclei recorded
      in the histologically normal-appearing mucosa of patients with either colorectal
      adenoma or adenocarcinoma exhibited differences in karyometric features in
      comparison with nuclei recorded in rectal mucosa from patients who were free of a
      colonic lesion. These differences were expressed to the same extent in tissue
      adjacent to the lesions and in normal-appearing tissue as distant as the rectum.
      CONCLUSIONS: The nuclear chromatin pattern may serve as an integrating biomarker
      for a preneoplastic development. The field effect might provide an end point in
      chemopreventive intervention trials.

PMID- 18086778
TI  - MDM2 promoter polymorphism SNP309 contributes to tumor susceptibility: evidence
      from 21 case-control studies.
AB  - Since the identification of a well-characterized functional polymorphism named
      SNP309 in MDM2, abundant studies were published in the last 2 years to evaluate
      the association between SNP309 and tumor risk in diverse populations. However,
      the results remain conflicting rather than conclusive. Because a single study may
      have been underpowered to detect the effect of low-penetrance genes, a
      quantitative synthesis to accumulate data from different studies may provide
      better evidence on the association of genetic variant with tumor susceptibility.
      We conducted a meta-analysis on 14,770 cases with different tumor types and
      14,524 controls from 25 published case-control studies to estimate the effect of
      SNP309 on tumor risk, as well as to quantify the potential between-study
      heterogeneity. We found that variant homozygote 309GG was associated with a
      significantly increased risk of all types of tumors [homozygote comparison: odds
      ratio (OR), 1.17, 95% confidential interval (95% CI), 1.04-1.33, P = 0.0002 for
      heterogeneity test; recessive model comparison: OR, 1.15, 95% CI, 1.03-1.28, P =
      0.0005 for heterogeneity test]. Tumor type and ethnicity contributed to the
      substantial heterogeneity (69.5% for homozygote comparison and 77.2% for
      recessive model comparison). The analyses suggest that MDM2 SNP309 serves as a
      low-penetrance susceptibility tumor marker. Further large studies incorporate
      quantitative detection of different p53-responsible environmental stresses, p53
      mutation status, and also functional genetic variants in p53-MDM2-related genes
      are warranted.

PMID- 18086779
TI  - Time trend and geographic patterns of lung adenocarcinoma in the United States,
      1973-2002.
AB  - OBJECTIVE: To find the major factor explaining the substantial increase in
      incidence of adenocarcinoma of the lung (ADL), we observed its temporal trend,
      distributions in geographic areas and populations, and compared them with the
      distributions of air pollution and low-tar cigarette consumption in time, place,
      and populations. METHODS: The temporal and spatial patterns of ADL were compared
      with the level of nitrogen oxides (NO(x)) emissions as well as the use of low-tar
      cigarettes. RESULTS: Similar increasing trends followed by declining trends were
      seen in emission levels of NO(x) and ADL incidence rates. These trends peak about
      20 years earlier for NO(x) levels than for ADL incidence. Incidence rates of ADL
      in high NO(x) emission areas were substantially higher than those in low NO(x)
      emission areas. Incidence rates of ADL in Black males are about 50% higher than
      in White males and can be explained by the differences in air quality related to
      residence site and size. CONCLUSIONS: The descriptive epidemiologic data help
      generate the hypothesis that long-term exposure to low-dose NO(x) may play a
      major role in causing steep increases in past ADL incidence rates. There is an
      urgent need to conduct further studies to determine whether the association is a
      causal relationship between long-term, low-dose exposure to NO(x) and ADL.

PMID- 18086780
TI  - Secondhand smoke exposure in public places in Guatemala: comparison with other
      Latin American countries.
AB  - OBJECTIVE: To measure secondhand smoke levels in workplaces in Guatemala and to
      compare exposure to levels in other Latin American cities. METHODS: Exposure was
      estimated by passive sampling of vapor phase nicotine using a filter badge.
      Filters were placed in 1 hospital, 1 school, 2 universities, 1 government
      building, the airport, and 10 restaurants/bars. In total, 103 filters were
      deployed (plus 7 duplicates and 10 blanks). Nicotine (microg/m(3)) was measured
      by gas chromatography. Medians [interquartile ranges (IQR)] of nicotine
      concentrations were reported and compared with other Latin American cities. A
      survey about attitudes for smoke-free workplaces was distributed among employees.
      RESULTS: Nicotine was detected in most (68%) locations surveyed (including
      workplaces where smoking is banned). The highest levels were found in bars
      [median, 4.58 microg/m(3) (IQR, 1.71-6.44)] and restaurants [median, 0.56
      microg/m(3) (IQR, 0.46-0.71)]. Nicotine concentrations in bars and restaurants
      were 710 and 114 times higher, respectively, compared with hospital
      concentrations after adjustment for smoking ban signs, type of ventilation, and
      volume of the area. Support for smoke-free environments was high, except in
      bar/restaurant and airport workers. Airborne nicotine levels in Guatemala were
      similar to those found in other Latin American cities. CONCLUSION: In Guatemala,
      exposure to secondhand smoke is highly prevalent. Workers in bars and restaurants
      are disproportionately exposed to secondhand smoke compared with other workers.
      There is an urgent need for complete smoke-free legislation and for educating
      workers about the benefits of smoke-free workplaces.

PMID- 18086781
TI  - Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA
      repair and cell cycle control pathways.
AB  - The DNA repair systems maintain the integrity of the human genome and cell cycle
      checkpoints are a critical component of the cellular response to DNA damage. We
      hypothesized that genetic variants in DNA repair and cell cycle control pathways
      will influence the predisposition to lung cancer, and studied 27 variants in 17
      DNA repair enzymes and 10 variants in eight cell cycle control genes in 1,604
      lung cancer patients and 2,053 controls. To improve the estimation of risks for
      specific variants, we applied a Bayesian approach in which we allowed the prior
      knowledge regarding the evolutionary biology and physicochemical properties of
      the variant to be incorporated into the hierarchical model. Based on the
      estimation from the hierarchical modeling, subjects who carried OGG1 326C/326C
      homozygotes, MGMT 143V or 178R, and CHEK2 157I had an odds ratio of lung cancer
      equal to 1.45 [95% confidence interval (95% CI), 1.05-2.00], 1.18 (95% CI, 1.01
      1.40), and 1.58 (95% CI, 1.14-2.17). The association of CHEK2 157I seems to be
      overestimated in the conventional analysis. Nevertheless, this association seems
      to be robust in the hierarchical modeling. None of the pathways seem to have a
      prominent effect. In general, our study supports the notion that sequence
      variation may explain at least some of the variation of inherited susceptibility.
      In particular, further investigation of OGG1, MGMT, and CHEK2 focusing on the
      genetic regions where the present markers are located or the haplotype blocks
      tightly linked with these markers might be warranted.

PMID- 18086782
TI  - Cytokine genes and pain severity in lung cancer: exploring the influence of TNF
      alpha-308 G/A IL6-174G/C and IL8-251T/A.
AB  - INTRODUCTION: Cytokines, aberrantly produced by cancer cells, have recently been
      implicated in the severity of cancer-related pain. We explored if polymorphisms
      in candidate cytokine genes could explain variability in self-reported pain in
      lung cancer patients of all stages. METHODS: Pain, clinical, and demographic
      variables were assessed at presentation and before any cancer treatment in 446
      Whites, 125 African-Americans, and 35 Hispanics with newly diagnosed non-small
      cell lung cancer. We genotyped functional single nucleotide polymorphisms in
      tumor necrosis factor-alpha (TNF-alpha -308 G/A), interleukin-6 (IL-6) -174G/C,
      and IL-8 -251T/A and determined their associations with pain severity. RESULTS:
      More African-Americans (35.5%) reported severe pain (score > or = 7 on a 0-10
      scale) relative to Hispanics (20%) and Whites (17%; P < 0.001). We did not
      observe any significant association between genotypes in TNF-alpha, IL-6, and IL
      8 and severe pain for either African-Americans or Hispanics, possibly due to
      small sample sizes. However, we observed that IL-8 (TT, 13%; TA + AA, 87%; P =
      0.04) was significantly associated with severe pain among White patients.
      Logistic regression analyses showed that after controlling for epidemiologic (age
      and sex), clinical (stage of disease, comorbidities), and symptom (depressed mood
      and fatigue) variables known to influence pain severity, variant alleles in IL-8 
      251T/A [odds ratio (OR), 2.35; 95% confidence interval (95% CI), 1.10-5.03; P =
      0.03] persisted as a significant factor for severe pain for White patients.
      CONCLUSIONS: In this preliminary analysis, we found evidence of the influence of
      cytokine genes on pain in White patients with lung cancer. Additional larger
      studies are needed to validate our findings. The long-term application is to
      tailored pain therapies.

PMID- 18086784
TI  - Joint effects of dietary trace metals and DNA repair capacity in lung cancer
      risk.
AB  - In a large case-control study, we previously reported that dietary intakes of
      zinc (Zn) and copper (Cu), but not selenium (Se), were inversely associated with
      lung cancer risk. Because Zn, Cu, Se, iron (Fe), and calcium (Ca) are important
      for maintaining DNA stability, we examined their associations with DNA repair
      capacity (DRC) measured by the lymphocyte host-cell reactivation assay in 1,139
      cases and 1,210 of the controls. Dietary intake was reported in a food frequency
      questionnaire. In multivariate analyses, compared to those with high dietary Cu +
      proficient DRC, the odds ratio (95% confidence interval) [OR (95% CI)] for lung
      cancer for low Cu + suboptimal DRC was 2.54 (1.97-3.27). Similar results were
      observed for men and women. These effects were more pronounced in older and lean
      subjects, those with late-stage disease, and those with a family history of
      cancer in first-degree relatives. Compared to subjects with high Zn + proficient
      DRC, the OR for lung cancer for low Zn + suboptimal DRC was 1.82 (95% CI, 1.41
      2.34), with pronounced effects in men, current smokers, subjects with longer
      duration of smoking, those with late-stage disease, or those with a family
      history of cancer. An OR of 1.94 (95% CI, 1.51-2.48) was observed for low Fe +
      suboptimal DRC compared with high Fe + proficient DRC, and pronounced effects
      appeared in older, lean subjects, those with longer duration of smoking, are
      heavier smokers, those with a late-stage disease, and those with a family history
      of cancer. No significant joint associations were seen for Se or Ca and DRC. Our
      joint associations between Cu-DRC, Zn-DRC and Fe-DRC and lung cancer risk require
      confirmation in prospective studies.

PMID- 18086783
TI  - CDX2 VDR polymorphism and colorectal cancer.
AB  - Studies suggest that polymorphisms of the vitamin D receptor (VDR) gene may
      influence colorectal cancer risk. In this study, we examine the association of
      the CDX2 VDR polymorphism (rs11568820) located in the 5'-untranslated region of
      the gene, and VDR haplotypes, including this polymorphism, with colon and rectal
      cancer using data from two large case-control studies of colon (N = 1,574 cases
      and 1,970 controls) and rectal (n = 791 cases and 999 controls) cancer. The
      frequency of the A allele of the CDX2 polymorphism was 19% among non-Hispanic
      white, 21% among Hispanic, 76% among African American, and 47% among Asian
      controls. The CDX2 polymorphism was not independently associated with either
      colon or rectal cancer, nor did it modify associations of dietary calcium,
      vitamin D, or fat with colon or rectal cancer. However, the bLFA haplotype which
      occurred in 6.5% of non-Hispanic white participants and 41.2% of African American
      participants was associated with an increased risk of colon cancer, and an odds
      ratio of 2.4 [95% confidence intervals (CI), 2.45 (1.38-4.38)]. The BSfG
      haplotype was associated with a 1.61 (95% CI, 1.05-2.49) increased risk of rectal
      but not colon cancer, whereas the BSFA haplotype was associated with a
      significantly reduced risk of rectal (odds ratio, 0.71; 95% CI, 0.52-0.97) but
      not colon cancer. These data suggest that haplotype analysis that encompasses
      different domains of the VDR gene might further our understanding of associations
      between the VDR gene and colon and rectal cancer.

PMID- 18086785
TI  - Predictors of enrollment into a familial cancer registry by individuals at high
      risk for BRCA1/2.
AB  - BACKGROUND: Registries of individuals at risk for hereditary cancer syndromes are
      an invaluable resource for cancer research, yet little is known about the
      predictors of enrollment in hereditary cancer registries. We sought to identify
      the factors that characterize individuals who enroll versus those who decline
      participation in a Familial Cancer Registry (FCR). We also sought to identify the
      factors associated with provision of a blood sample to the FCR. METHODS:
      Participants (n = 549) had a 10% or greater prior probability of having a BRCA1/2
      mutation or were members of a family with a known BRCA1/2 mutation. RESULTS: Of
      549 participants, 81.1% (n = 445) enrolled in the FCR and 18.9% (n = 104)
      declined. Independent significant predictors of FCR participation included: lower
      anxiety (odds ratio(0.5 SD), 0.83; 95% confidence interval, 0.73-0.95) and being
      unaffected with breast or ovarian cancer (odds ratio, 0.52; 95% confidence
      interval, 0.39-0.67). Of the 445 FCR participants, 80.4% provided a blood sample
      whereas 19.6% declined, with blood sample provision predicted by being employed
      full time (odds ratio, 1.68; 95% confidence interval, 1.31-2.16). CONCLUSION:
      These findings have implications for the generalizability of results from
      research using hereditary cancer registry samples. Individuals who are affected
      with breast/ovarian cancer and have more anxiety are less likely to enroll in a
      hereditary cancer registry. Clinically, these results indicate that cancer
      registry enrollment strategies could benefit from the use of tailored approaches
      to increase the enrollment of individuals that are less likely to participate.

PMID- 18086786
TI  - Activated checkpoint kinase 2 expression and risk for oral squamous cell
      carcinoma.
AB  - BACKGROUND: Phosphoactivation of a DNA damage response molecule checkpoint kinase
      2 (pChk2) may be a marker of oral epithelial cells that have entered the
      precancerous and squamous cell carcinoma (SCC) stages. We explored whether there
      was selective expression of pChk2 in precancerous lesions but not in
      nonneoplastic tissue of the oral mucosa. EXPERIMENTAL DESIGN: In a retrospective
      cohort design, 96 biopsied clinical leukoplakias and erythroplakias with known
      subsequent progression to SCC were identified from 48 subjects and assigned as
      the cases group. Expression status of pChk2 was compared with that of the 97
      leukoplakias and erythroplakias that did not progress to SCC (control groups) by
      immunohistochemical analysis. Included in both groups were lesions with
      histologically confirmed dysplasia and those that lacked histologic evidence of
      atypia. RESULTS: Subjects with pChk2-positive but histology-negative (for atypia)
      lesions had an 8.6 times higher risk of developing SCC compared with those with
      pChk2-negative and histology-negative lesions. Overall, the presence of
      detectable pChk2 staining was able to identify lesions at risk of developing SCC
      within 3 years with a sensitivity of 85.2%, specificity of 74.2%, and predictive
      accuracy of 78.2% (odds ratio, 19.9; 95% confidence interval, 7.3-55.5).
      CONCLUSION: This is the first study to include histologically nonatypical cases
      in the analysis of a putative biomarker for oral precancerous lesions. Our data
      show that pChk2 merits further investigation as a promising biomarker that can
      discriminate those lesions at risk for developing SCC, regardless of histologic
      evidence for atypia.

PMID- 18086787
TI  - Changes in breast cancer incidence rates in the United States by histologic
      subtype and race/ethnicity, 1995 to 2004.
AB  - Breast cancer incidence rates rose throughout the 1980s and 1990s in the United
      States but have recently declined through 2004. Studies reporting this decline
      primarily attribute it to the sharp decline in menopausal hormone use following
      publication of the Women's Health Initiative trial results. However, they have
      not stratified rates by either histologic type or race/ethnicity, which could
      further inform contributors to these trends. Using data from 13 cancer registries
      that participate in the Surveillance, Epidemiology, and End Results program, we
      evaluated annual percent changes (APC) in breast cancer incidence rates from 1995
      to 2004 by histologic type and race/ethnicity for intervals identified using
      joinpoint regression. Invasive ductal carcinoma and invasive lobular carcinoma
      incidence rates fell steadily from 1998 to 2004 [APC, -3.07% (95% confidence
      interval, -4.10 to -2.02) and APC, -3.18% (95% confidence interval, -5.18 to 
      1.03), respectively]. Declines in rates of breast cancer overall and invasive
      ductal carcinoma were primarily limited to women > or = 50 years of age and to
      non-Hispanic whites and Asian/Pacific Islanders, and declines in rates of
      invasive lobular carcinoma were primarily limited to non-Hispanic whites. The
      majority of these declines began around 1998 and all began before 2002 when the
      Women's Health Initiative trial results were published; thus, the abrupt decline
      in hormone therapy use starting in 2002 is unlikely to be primarily responsible
      for the recent decline in breast cancer rates. The declines observed thus far are
      likely attributable to saturation of screening, although further declines related
      to the widespread cessation of hormone use may follow.

PMID- 18086788
TI  - Associations of serum carotenoid levels with serum insulin-like growth factor-i
      and insulin-like growth factor binding protein-3 levels in black men and white
      men.

PMID- 18086789
TI  - Lack of association between serum levels of 25-hydroxyvitamin D and the
      subsequent risk of prostate cancer in Finnish men.

PMID- 18086790
TI  - Nutrients involved in one-carbon metabolism and risk of breast cancer among
      premenopausal women.
AB  - Folate, vitamin B6, vitamin B12, methionine, choline, and betaine are nutrients
      involved in one-carbon metabolism and have been hypothesized to reduce the risk
      of breast cancer. However, previous epidemiologic studies on most of these
      nutrients and breast cancer risk have been inconclusive and have included
      primarily postmenopausal women. No study has examined choline and betaine in
      relation to breast cancer risk. Therefore, we examined the intake of these
      nutrients in relation to breast cancer risk among 90,663 premenopausal women ages
      26 to 46 years in 1991 in the Nurses' Health Study II. Nutrient intake was
      assessed with a validated food frequency questionnaire in 1991, 1995, and 1999.
      During 12 years of follow-up from 1991 to 2003, we documented 1,032 incident
      cases of invasive breast cancer. Overall, none of the nutrients was associated
      with risk of breast cancer. The results were similar by levels of alcohol intake
      and folate intake and for estrogen receptor-negative breast cancer. In
      conclusion, we found no evidence that higher intakes of nutrients involved in one
      carbon metabolism reduce risk of breast cancer among premenopausal women.

PMID- 18086791
TI  - Constitutional cytogenetic analysis in men with hereditary testicular germ cell
      tumor: no evidence of disease-related abnormalities.

PMID- 18086792
TI  - Effect of soy protein on testosterone levels.

PMID- 18086794
TI  - Clinical cancer advances 2007: major research advances in cancer treatment,
      prevention, and screening--a report from the American Society of Clinical
      Oncology.
AB  - A MESSAGE FROM ASCO'S PRESIDENT: For the third year, the American Society of
      Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research
      Advances in Cancer Treatment, Prevention, and Screening, an annual review of the
      most significant cancer research presented or published over the past year. ASCO
      publishes this report to demonstrate the important progress being made on the
      front lines of clinical cancer research today. The report is intended to give all
      those with an interest in cancer care-the general public, cancer patients and
      organizations, policymakers, oncologists, and other medical professionals-an
      accessible summary of the year's most important cancer research advances. These
      pages report on the use of magnetic resonance imaging for breast cancer
      screening, the association between hormone replacement therapy and breast cancer
      incidence, the link between human papillomavirus and head and neck cancers, and
      the use of radiation therapy to prevent lung cancer from spreading. They also
      report on effective new targeted therapies for cancers that have been
      historically difficult to treat, such as liver cancer and kidney cancer, among
      many others. A total of 24 advances are featured in this year's report. These
      advances and many more over the past several years show that the nation's long
      term investment in cancer research is paying off. But there are disturbing signs
      that progress could slow. We are now in the midst of the longest sustained period
      of flat government funding for cancer research in history. The budgets for the
      National Institutes of Health and the National Cancer Institute (NCI) have been
      unchanged for four years. When adjusted for inflation, cancer research funding
      has actually declined 12% since 2004. These budget constraints limit the NCI's
      ability to fund promising cancer research. In the past several years the number
      of grants that the NCI has been able to fund has significantly decreased; this
      year, in response to just the threat of a 10% budget cut, the nation's Clinical
      Trials Cooperative Groups reduced the number of patients participating in
      clinical trials by almost 2,000 and senior researchers report that many of the
      brightest young minds no longer see the promise of a career in science, choosing
      other careers instead. It's time to renew the nation's commitment to cancer
      research. Without additional support, the opportunity to build on the
      extraordinary progress to date will be lost or delayed. This report demonstrates
      the essential role that clinical cancer research plays in finding new and better
      ways to care for the more than 1.4 million people expected to be diagnosed with
      cancer this year. I want to thank the Editorial Board members, the Specialty
      Editors, and the ASCO Cancer Communications Committee for their dedicated work to
      develop this report. I hope you find it useful. Sincerely, Nancy E. Davidson, MD
      President American Society of Clinical Oncology.

PMID- 18086795
TI  - Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen +
      triptorelin in premenopausal patients with early breast cancer.
AB  - PURPOSE: To compare the endocrine effects of 6 months of adjuvant treatment with
      letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with
      early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment
      Bone Effects study). PATIENTS AND METHODS: Prospectively collected hormonal data
      were available for 81 premenopausal women, of whom 30 were assigned to receive
      tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/-
      zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), Delta4-androstenedione, testosterone,
      dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH),
      and cortisol were measured at baseline and after 6 months of treatment. For each
      hormone, 6-month values were compared between treatment groups by the Wilcoxon
      Mann-Whitney exact test. RESULTS: Median age was 44 years for both groups of
      patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger
      suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and
      cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median
      FSH serum levels were suppressed in both groups, but such suppression was lower
      among patients receiving letrozole, who showed significantly higher median FSH
      serum levels (P < .0001). No significant differences were observed for
      testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone
      between the two groups of patients. CONCLUSION: Letrozole in combination with
      triptorelin induces a more intense estrogen suppression than tamoxifen +
      triptorelin in premenopausal patients with early breast cancer.

PMID- 18086796
TI  - Reduced-intensity conditioning compared with conventional allogeneic stem-cell
      transplantation in relapsed or refractory Hodgkin's lymphoma: an analysis from
      the Lymphoma Working Party of the European Group for Blood and Marrow
      Transplantation.
AB  - PURPOSE: To compare the clinical outcome in terms of nonrelapse mortality (NRM),
      relapse rate (RR), overall survival (OS), and progression-free survival (PFS) in
      patients with relapsed Hodgkin's lymphoma (HL) treated with reduced-intensity
      conditioning (RIC) or myeloablative conditioning followed by allogeneic stem-cell
      transplantation (alloSCT). PATIENTS AND METHODS: A total of 168 patients with HL
      undergoing a first alloSCT (RIC, n = 89; myeloablative conditioning, n = 79)
      between January 1997 and December 2001 and registered in the European Group for
      Blood and Marrow Transplantation database were analyzed. RESULTS: NRM was
      significantly decreased in the RIC group (hazard ratio [HR], 2.85; 95% CI, 1.62
      to 5.02; P < .001). OS was better in the RIC group (HR, 2.05; 95% CI, 1.27 to
      3.29; P = .04) and there was a trend for better PFS in the RIC group (HR, 1.53;
      95% CI, 0.97 to 2.40; P = .07). RR was higher in the RIC group in univariate but
      not in multivariate analysis. The development of chronic graft-versus-host
      disease (GVHD) significantly decreased the incidence of relapse, which translated
      into a trend for a better PFS. CONCLUSION: The lower incidence of NRM in the RIC
      group is encouraging, particularly because these patients experienced adverse
      pretransplantation characteristics more frequently. This analysis also indicates
      the existence of a graft-versus-HL effect correlated to the development of GVHD.
      Additional efforts to reduce the high RR seen in both groups of patients will be
      necessary to improve the modest PFS (31% v 27%) and OS (59% v 36%) for patients
      prepared with RIC or myeloablative conditioning.

PMID- 18086797
TI  - LMO2 protein expression predicts survival in patients with diffuse large B-cell
      lymphoma treated with anthracycline-based chemotherapy with and without
      rituximab.
AB  - PURPOSE: The heterogeneity of diffuse large B-cell lymphoma (DLBCL) has prompted
      the search for new markers that can accurately separate prognostic risk groups.
      We previously showed in a multivariate model that LMO2 mRNA was a strong
      predictor of superior outcome in DLBCL patients. Here, we tested the prognostic
      impact of LMO2 protein expression in DLBCL patients treated with anthracycline
      based chemotherapy with or without rituximab. PATIENTS AND METHODS: DLBCL
      patients treated with anthracycline-based chemotherapy alone (263 patients) or
      with the addition of rituximab (80 patients) were studied using
      immunohistochemistry for LMO2 on tissue microarrays of original biopsies.
      Staining results were correlated with outcome. RESULTS: In anthracycline-treated
      patients, LMO2 protein expression was significantly correlated with improved
      overall survival (OS) and progression-free survival (PFS) in univariate analyses
      (OS, P = .018; PFS, P = .010) and was a significant predictor independent of the
      clinical International Prognostic Index (IPI) in multivariate analysis.
      Similarly, in patients treated with the combination of anthracycline-containing
      regimens and rituximab, LMO2 protein expression was also significantly correlated
      with improved OS and PFS (OS, P = .005; PFS, P = .009) and was a significant
      predictor independent of the IPI in multivariate analysis. CONCLUSION: We
      conclude that LMO2 protein expression is a prognostic marker in DLBCL patients
      treated with anthracycline-based regimens alone or in combination with rituximab.
      After further validation, immunohistologic analysis of LMO2 protein expression
      may become a practical assay for newly diagnosed DLBCL patients to optimize their
      clinical management.

PMID- 18086798
TI  - High numbers of tumor-associated macrophages have an adverse prognostic value
      that can be circumvented by rituximab in patients with follicular lymphoma
      enrolled onto the GELA-GOELAMS FL-2000 trial.
AB  - PURPOSE: High amounts of intratumoral macrophages have been shown to correlate
      with poor prognosis in patients with follicular lymphoma (FL) treated with
      chemotherapy without rituximab. We tried to establish whether intratumoral
      macrophage count (MC) definitely is able to predict the outcome of FL patients in
      the rituximab era. PATIENTS AND METHODS: We analyzed immunohistochemical CD68
      expression in 194 FL patients from the FL-2000 trial, randomly assigned to
      receive cyclophosphamide, doxorubicin, etoposide, prednisolone, and interferon
      (CHVP-I) or rituximab plus CHVP-I. Immunohistochemistry was performed on paraffin
      sections using anti-CD68 KP1 antibody, and stained macrophages were scored on
      high-power field (hpf) in either intrafollicular (IF) or extrafollicular (EF)
      areas. RESULTS: For IF MC, the best cutoff point was estimated at 10
      macrophages/hpf. Low IF MC was significantly associated with a better event-free
      survival (EFS; P = .011). However, this effect was observed only in the CHVP-I
      arm (P = .012) and not in the rituximab plus CHVP-I arm. Using a cutoff of 15 IF
      MC, we found no significant association with EFS. For EF MC, fewer than 22
      macrophages/hpf were associated with better EFS in the CHVP-I arm (P = .02) but
      not in the rituximab plus CHVP-I arm. CONCLUSION: These results show that MC can
      predict outcome of FL patients and that rituximab is able to circumvent the
      unfavorable outcome associated with high MC.

PMID- 18086799
TI  - Lymphocyte-predominant and classical Hodgkin's lymphoma: a comprehensive analysis
      from the German Hodgkin Study Group.
AB  - PURPOSE: Lymphocyte-predominant Hodgkin's lymphoma (LPHL) is rare and differs in
      histologic and clinical presentation from classical Hodgkin's lymphoma (cHL). To
      shed more light on the prognosis and outcome of LPHL, we reviewed all LPHL
      patients registered in the German Hodgkin Study Group (GHSG) database, comparing
      patient characteristics and treatment outcome with cHL patients. PATIENTS AND
      METHODS: We analyzed retrospectively 8,298 HL patients treated within the GHSG
      trials HD4 to HD12, of whom 394 had LPHL and 7,904 had cHL. RESULTS: Complete
      remission and unconfirmed complete remission after first-line treatment was
      achieved in 91.6% v 85.9% of patients in early favorable stages, 85.7% v 83.3% of
      patients in early unfavorable stages, and 76.8% v 77.8% of patients in advanced
      stages of LPHL compared with cHL, respectively. Tumor control (freedom from
      treatment failure [FFTF]) for LPHL and cHL patients at a median observation of 50
      months was 88% and 82% (P = .0093) and overall survival (OS) was 96% and 92%,
      respectively (P = .0166). In LPHL patients, negative prognostic factors were
      advanced stage (P = .0092), Hb less than 10.5 g/dL (P = .0171), and lymphopenia
      (P = .010) for FFTF. Age >or= 45 years (P = .0125), advanced stage (P = .0153),
      and Hb less than 10.5 g/dL (P = .0014) were negative prognostic factors for OS.
      CONCLUSION: The better prognosis of LPHL as compared with cHL might allow
      different treatment strategies, particularly for early-stage LPHL patients.

PMID- 18086800
TI  - Survival after adjuvant oophorectomy and tamoxifen in operable breast cancer in
      premenopausal women.
AB  - PURPOSE: Worldwide, approximately 750,000 new cases of breast cancer are
      diagnosed annually in premenopausal women with limited economic resources. Longer
      term survival benefits from adjuvant therapies in such women with operable breast
      cancer are unknown. PATIENTS AND METHODS: From 1993 to 1999, we recruited 709
      premenopausal women with operable breast cancer to a multisite randomized
      clinical trial of adjuvant oophorectomy and tamoxifen for 5 years or observation
      and this combined hormonal therapy on recurrence. RESULTS: With a median follow
      up of 7.0 years, disease-free and overall survival were significantly improved
      with the adjuvant treatment (log-rank P = .0003 and .0002, respectively). Five
      year disease-free survival (DFS) probabilities of 74% and 61% (95% CI for
      difference, 7% to 21%) and overall survival (OS) rates of 78% and 71% (95% CI for
      difference, 1% to 21%) were observed in the adjuvant and observation groups. Ten
      year DFS probabilities of 62% and 51% (95% CI for difference, 4% to 22%) and OS
      probabilities of 70% and 52% (95% CI for difference, 6% to 34%) between adjuvant
      and observation groups, respectively, were observed. In the subset of estrogen
      receptor-positive patients, 5-year DFS probabilities were 83% and 61%, and 10
      year DFS probabilities were 66% and 47%, while 5-year OS probabilities were 88%
      and 74%, and 10-year OS probabilities were 82% and 49% in the adjuvant and
      observation groups, respectively. CONCLUSION: In premenopausal women with
      operable breast cancer not selected for estrogen receptor status or with estrogen
      receptor-positive tumors, 5- and 10-year DFS and OS rates are significantly
      improved following adjuvant oophorectomy and tamoxifen.

PMID- 18086801
TI  - Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic
      syndrome after reduced-intensity conditioning allogeneic hematopoietic
      transplantation: chronic graft-versus-host disease is the strongest factor
      improving survival.
AB  - PURPOSE: Reduced-intensity conditioning (RIC) for allogeneic stem-cell
      transplantation (allo-SCT) reduces nonrelapse mortality (NRM). This reduction
      makes it possible for patients who are ineligible for high-dose myeloablative
      conditioning allo-SCT to benefit from graft-versus-leukemia reaction. In this
      multicenter, prospective study of patients with acute myeloid leukemia (AML) and
      high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of RIC
      allo-SCT from a human leukocyte antigen-identical sibling by using a regimen that
      uses fludarabine and busulfan. PATIENTS AND METHODS: Ninety-three patients with
      AML (n = 59) and MDS (n = 34) were included, and the median age was of 53 years.
      Follow-up for survivors was 43 months (range, 3 to 89 months). The conditioning
      regimen consisted of fludarabine (150 mg/m(2)) and oral busulfan (8 to 10 mg/kg).
      All except one patient received mobilized peripheral blood stem cells. Graft
      versus-host disease (GVHD) prophylaxis consisted of cyslosporine and methotrexate
      or mycophenolate mofetil. RESULTS: The 100-day, 1-year, and 4-year incidences of
      NRM were 8, 16%, and 21%, respectively. The 1- and 4-year relapse cumulative
      incidences were 23% and 37%, respectively, and leukemia recurrence was the main
      cause of death. The 4-year disease-free survival (DFS) and overall survival (OS)
      rates were 43% and 45%, respectively. The 4-year cumulative incidence of chronic
      GVHD was 53% (45% extensive), and its development was the major factor associated
      with lower relapse incidence and improved DFS and OS. CONCLUSION: Our results
      confirm the capacity of this RIC regimen to obtain long-term remissions in
      patients ineligible for a conventional allo-SCT. The results suggest an important
      role of the development of chronic GVHD in reducing relapse and improving DFS and
      OS.

PMID- 18086802
TI  - Quality of life and survival in the 2 years after surgery for non small-cell lung
      cancer.
AB  - PURPOSE: Although surgery for early-stage non-small-cell lung cancer (NSCLC) is
      known to have a substantial impact on health-related quality of life (HRQOL),
      there are few published studies about HRQOL in the longer term. This article
      examines HRQOL and survival in the 2 years after surgery. PATIENTS AND METHODS:
      Patients with clinical stage I or II NSCLC (n = 173) completed HRQOL
      questionnaires before surgery, at discharge, 1 month after surgery, and then
      every 4 months for 2 years. HRQOL was measured with a generic cancer
      questionnaire (European Organisation for Research and Treatment of Cancer Quality
      of Life Questionnaire [EORTC-QLQ] C30) and a lung cancer-specific questionnaire
      (EORTC QLQ-LC13). Data were analyzed to examine the impact of surgery and any
      subsequent therapy, and to describe the trajectories of those who remained
      disease free at 2 years and those with recurrent cancer diagnosed during follow
      up. RESULTS: Disease recurred within 2 years for 36% of patients and 2-year
      survival was 65%. Surgery substantially reduced HRQOL across all dimensions
      except emotional functioning. HRQOL improved in the 2 years after surgery for
      patients without disease recurrence, although approximately half continued to
      experience symptoms and functional limitations. For those with recurrence within
      2 years, there was some early postoperative recovery in HRQOL, with subsequent
      deterioration across most dimensions. CONCLUSION: Surgery had a substantial
      impact on HRQOL, and although many disease-free survivors experienced recovery,
      some lived with long-term HRQOL impairment. HRQOL generally worsened with disease
      recurrence. The study results are important for informed decision making and
      ongoing supportive care for patients with operable NSCLC.

PMID- 18086803
TI  - Restriction site-dependent PCR: an efficient technique for fast cloning of new
      genes of microorganisms.
AB  - New bioactive proteins need to be screened from various microorganisms for the
      increasing need for industrial and pharmaceutical peptide, proteins, or enzymes.
      A novel polymerase chain reaction (PCR) method, restriction site-dependent PCR
      (RSD-PCR), was designed for rapid new genes cloning from genomic DNA. RSD-PCR
      strategy is based on these principles: (i) restriction sites disperse throughout
      genomes are candidacy for universal pairing; (ii) a universal primer is a
      combination of a 3'-end of selected restriction sites, and a 5'-end of
      degenerated sequence. A two-round PCR protocol was designed and optimized for the
      RSD-PCR: amplify the single strand target template from genomic DNA by a specific
      primer and amplify the target gene by using the specific primer and one of the
      universal RSD-primers. The optimized RSD-PCR was successfully applied in
      chromosome walking using specific internal primers, and cloning of new genes
      using degenerated primers derived from NH2-terminal amino acid sequence of
      protein.

PMID- 18086804
TI  - Progesterone acts via progesterone receptors A and B to regulate breast cancer
      resistance protein expression.
AB  - The breast cancer resistance protein (BCRP; ABCG2) is an ATP-dependent efflux
      multidrug transporter that belongs to the G family of half-transporters that
      consist of six transmembrane-spanning domains and must homodimerize to form the
      active membrane transporter. It is expressed in the apical plasma membrane domain
      of the small intestine, endothelium, and liver, where it has been shown to play
      an important role in limiting drug absorption and distribution and in enhancing
      drug clearance, respectively. BCRP is also expressed in the apical membrane of
      mammary alveolar epithelia, where it mediates efflux of substrates into milk, and
      in the placental syncytiotro-phoblasts, where it reduces fetal exposure to these
      substrates. BCRP substrates include numerous drugs (topotecan, nitrofurantoin,
      cimetidine) as well as food carcinogens (2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine) and the vitamins riboflavin and folic acid. BCRP expression is
      regulated by a number of nuclear transcription factors, including the peroxisome
      proliferator-activated receptor-gamma and Hif-1. This issue of Molecular
      Pharmacology includes a study (p. 845) now conclusively demonstrating that
      progesterone acts via the progesterone A and B receptors to regulate BCRP
      expression in a placental cell line.

PMID- 18086805
TI  - Viable Borrelia burgdorferi enhances interleukin-10 production and suppresses
      activation of murine macrophages.
AB  - Although it is capable of eliciting strong innate and adaptive immune responses,
      Borrelia burgdorferi often evades immune clearance through largely unknown
      mechanisms. Our previous studies determined that infected interlukin-10-/- (IL-10
      /-) mice show significantly lower B. burgdorferi levels than wild-type (B6) mice
      and that IL-10 inhibits innate immune responses critical for controlling B.
      burgdorferi infection. To determine whether virulent B. burgdorferi
      preferentially enhances IL-10 production, we developed an in vitro coculture
      medium (RPMI.B) in which both B. burgdorferi and primary macrophages (Mphis)
      remain viable. B. burgdorferi grew at similar rates and was able to regulate
      expression of immunoreactive proteins with similar kinetics in RPMI.B and in
      traditional BSK medium; in contrast, B. burgdorferi cultured in conventional
      tissue culture medium (RPMI) rapidly lost viability. Coculture of viable B.
      burgdorferi in RPMI.B with Mphis resulted in more rapid and significant increases
      in IL-10 transcripts and secreted proteins than coculture with nonviable B.
      burgdorferi in RPMI, which corresponded with decreased production of
      proinflammatory cytokines. Addition of live B. burgdorferi to Mphis in RPMI.B
      also elicited substantially higher IL-10 levels than heat-killed bacteria
      elicited, confirming that increased IL-10 production was not inherent to
      coculture in RPMI.B. Transfer of supernatants from B. burgdorferi-stimulated
      Mphis into naive Mphi cultures resulted in suppressed activation upon subsequent
      stimulation with different bacterial agonists, and this suppression was obviated
      by IL-10-specific antibody. In vivo analyses determined that murine skin samples
      exhibited substantial upregulation of IL-10 within 24 h of injection of B.
      burgdorferi. Together, these results suggest that viable B. burgdorferi can
      suppress early Mphi responses during infection by causing increased release of IL
      10.

PMID- 18086806
TI  - Proapoptotic Bcl-2 family member Bim promotes persistent infection and limits
      protective immunity.
AB  - Following the peak of the T-cell response, most of the activated effector T cells
      die by apoptosis driven by the proapoptotic Bcl-2 family member Bim (Bcl-2
      interacting mediator of death). Whether the absence of Bim-mediated T-cell
      apoptosis can affect protective immunity remains unclear. Here, we used a mouse
      model of Leishmania major infection, in which parasite persistence and protective
      immunity are controlled by an equilibrium reached between parasite-specific gamma
      interferon (IFN-gamma)-producing effector T cells and interleukin-10 (IL-10)
      producing CD4+ CD25+ T regulatory cells. To further understand the role of Bim
      mediated apoptosis in persistent infection and protective immunity, we infected
      Bim-/- mice with L. major. We found that the initial parasite growth and lesion
      development were similar in Bim-/- and wild-type mice after primary L. major
      infection. However, at later times after infection, Bim-/- mice had significantly
      increased L. major-specific CD4+ T-cell responses and were resistant to
      persistent infection. Interestingly, despite their resistance to primary L. major
      infection, Bim-/- mice displayed significantly enhanced protection against
      challenge with L. major. Increased resistance to challenge in Bim-/- mice was
      associated with a significant increase in the number of L. major-specific IFN
      gamma-producing CD4+ T cells and a lack of IL-10 production at the challenge
      site. Taken together, these data suggest that Bim limits protective immunity and
      that the absence of Bim allows the host to bypass antigen persistence for
      maintenance of immunity against reinfection.

PMID- 18086807
TI  - Participation of the serine-rich Entamoeba histolytica protein in amebic
      phagocytosis of apoptotic host cells.
AB  - Entamoeba histolytica is an intestinal ameba that causes dysentery and liver
      abscesses. Cytotoxicity and phagocytosis of host cells characterize invasive E.
      histolytica infection. Prior to phagocytosis of host cells, E. histolytica
      induces apoptotic host cell death, using a mechanism that requires contact via an
      amebic galactose-specific lectin. However, lectin inhibition only partially
      blocks phagocytosis of already dead cells, implicating at least one additional
      receptor in phagocytosis. To identify receptors for engulfment of apoptotic
      cells, monoclonal antibodies against E. histolytica membrane antigens were
      screened for inhibition of phagocytosis. Of 43 antibodies screened, one blocked
      lectin-independent uptake of apoptotic cells, with >90% inhibition at a dose of
      20 microg/ml (P < 0.0003 versus control). The same antibody also inhibited
      adherence to apoptotic lymphocytes and, to a lesser extent, adherence to and
      killing of viable lymphocytes. The antigen recognized by the inhibitory antibody
      was purified by affinity chromatography and identified by liquid chromatography
      mass spectrometry as the serine-rich E. histolytica protein (SREHP). Consistent
      with this, the inhibitory antibody bound to recombinant SREHP present in
      bacterial lysates on immunoblots. The SREHP is an abundant immunogenic surface
      protein of unclear function. The results of this unbiased antibody screen
      strongly implicate the SREHP as a participant in E. histolytica phagocytosis and
      suggest that it may play an important role in adherence to apoptotic cells.

PMID- 18086808
TI  - A Salmonella enterica serovar typhimurium succinate dehydrogenase/fumarate
      reductase double mutant is avirulent and immunogenic in BALB/c mice.
AB  - Previously we showed that the tricarboxylic acid (TCA) cycle operates as a full
      cycle during Salmonella enterica serovar Typhimurium SR-11 peroral infection of
      BALB/c mice (M. Tchawa Yimga et al., Infect. Immun. 74:1130-1140, 2006). The
      evidence was that a DeltasucCD mutant (succinyl coenzyme A [succinyl-CoA]
      synthetase), which prevents the conversion of succinyl-CoA to succinate, and a
      DeltasdhCDA mutant (succinate dehydrogenase), which blocks the conversion of
      succinate to fumarate, were both attenuated, whereas an SR-11 DeltaaspA mutant
      (aspartase) and an SR-11 DeltafrdABCD mutant (fumarate reductase), deficient in
      the ability to run the reductive branch of the TCA cycle, were fully virulent. In
      the present study, evidence is presented that a serovar Typhimurium SR-11
      DeltafrdABCD DeltasdhCDA double mutant is avirulent in BALB/c mice and protective
      against subsequent infection with the virulent serovar Typhimurium SR-11 wild
      type strain via the peroral route and is highly attenuated via the
      intraperitoneal route. These results suggest that fumarate reductase, which
      normally runs in the reductive pathway in the opposite direction of succinate
      dehydrogenase, can replace it during infection by running in the same direction
      as succinate dehydrogenase in order to run a full TCA cycle in an SR-11
      DeltasdhCDA mutant. The data also suggest that the conversion of succinate to
      fumarate plays a key role in serovar Typhimurium virulence. Moreover, the data
      raise the possibility that S. enterica DeltafrdABCD DeltasdhCDA double mutants
      and DeltafrdABCD DeltasdhCDA double mutants of other intracellular bacterial
      pathogens with complete TCA cycles may prove to be effective live vaccine strains
      for animals and humans.

PMID- 18086809
TI  - p38 mitogen-activated protein kinase mediates lipopolysaccharide and tumor
      necrosis factor alpha induction of shiga toxin 2 sensitivity in human umbilical
      vein endothelial cells.
AB  - Escherichia coli O157:H7 Shiga toxin 2 (Stx2), one of the causative agents of
      hemolytic-uremic syndrome, is toxic to endothelial cells, including primary
      cultured human umbilical vein endothelial cells (HUVEC). This sensitivity of
      cells to Stx2 can be increased with either lipopolysaccharide (LPS) or tumor
      necrosis factor alpha (TNF-alpha). The goal of the present study was to identify
      the intracellular signaling pathway(s) by which LPS and TNF-alpha sensitize HUVEC
      to the cytotoxic effects of Stx2. To identify these pathways, specific
      pharmacological inhibitors and small interfering RNAs were tested with cell
      viability endpoints. A time course and dose response experiment for HUVEC
      exposure to LPS and TNF-alpha showed that a relatively short exposure to either
      agonist was sufficient to sensitize the cells to Stx2 and that both agonists
      stimulated intracellular signaling pathways within a short time. Cell viability
      assays indicated that the p38 mitogen-activated protein kinase (MAPK) inhibitors
      SB202190 and SB203580 and the general protein synthesis inhibitor cycloheximide
      inhibited both the LPS and TNF-alpha sensitization of HUVEC to Stx2, while all
      other inhibitors tested did not inhibit this sensitization. Additionally,
      SB202190 reduced the cellular globotriaosylceramide content under LPS- and TNF
      alpha-induced conditions. In conclusion, our results show that LPS and TNF-alpha
      induction of Stx2 sensitivity in HUVEC is mediated through a pathway that
      includes p38 MAPK. These results indicate that inhibition of p38 MAPK in
      endothelial cells may protect a host from the deleterious effects of Stx2.

PMID- 18086810
TI  - Antigen delivered by anthrax lethal toxin induces the development of memory CD8+
      T cells that can be rapidly boosted and display effector functions.
AB  - Memory CD8+ T cells are essential for protective immunity against many
      intracellular pathogens; therefore, stimulation of this population of cells is an
      important goal of vaccination. We have previously shown that a detoxified
      derivative of Bacillus anthracis anthrax lethal toxin (LT) can deliver
      heterologous CD8+ T-cell epitopes to the major histocompatibility complex class I
      processing and presentation pathway of murine host cells and that immunization of
      mice with these LT-antigen fusion proteins leads to the induction of antigen
      specific CD8+ T cells. In this report we extend these findings to include a
      detailed characterization of the phenotypic and functional properties of the T
      cells stimulated by the LT-based system. We found that after an initial period of
      expansion and contraction, antigen-specific CD8+ T cells differentiated into a
      pool of memory cells that produced gamma interferon and displayed in vivo
      cytotoxic activity. The transition to memory cells appeared to be quite rapid
      based on an analysis of the phenotypic marker CD127 and the effectiveness of a
      booster immunization administered early after the initial immunization. We also
      investigated the composition of the memory T-cell pool induced by this system and
      found that while one immunization induced a mixture of effector memory T cells
      (CD62Llow) and central memory T cells (CD62Lhigh), a second immunization
      preferentially elevated the effector memory T-cell frequency. Finally, we
      demonstrated that mice that received prime-boost immunizations of LT-antigen
      proteins were more protected in a Listeria monocytogenes challenge model than
      mice that received only one immunization.

PMID- 18086811
TI  - Fluid secretion caused by aerolysin-like hemolysin of Aeromonas sobria in the
      intestines is due to stimulation of production of prostaglandin E2 via
      cyclooxygenase 2 by intestinal cells.
AB  - To clarify the mechanisms of diarrheal disease induced by Aeromonas sobria, we
      examined whether prostaglandin E2 (PGE2) was involved in the intestinal secretory
      action of A. sobria hemolysin by use of a mouse intestinal loop model. The amount
      of PGE2 in jejunal fluid and the fluid accumulation ratio were directly related
      to the dose of hemolysin. The increase over time in the level of PGE2 was similar
      to that of the accumulated fluid. In addition, hemolysin-induced fluid secretion
      and PGE2 synthesis were inhibited by the selective cyclooxygenase 2 (COX-2)
      inhibitor NS-398 but not the COX-1 inhibitor SC-560. Western blot analysis
      revealed that hemolysin increased the COX-2 protein levels but reduced the COX-1
      protein levels in mouse intestinal mucosa in vivo. These results suggest that
      PGE2 functions as an important mediator of diarrhea caused by hemolysin and that
      PGE2 is produced primarily through a COX-2-dependent mechanism. Subsequently, we
      examined the relationship between PGE2, cyclic AMP (cAMP), and cystic fibrosis
      transmembrane conductance regulator (CFTR) Cl- channels in mouse intestinal
      mucosa exposed to hemolysin. Hemolysin increased the levels of cAMP in the
      intestinal mucosa. NS-398 inhibited the increase in cAMP production, but SC-560
      did not. In addition, H-89, a cAMP-dependent protein kinase A (PKA) inhibitor,
      and glibenclamide, a CFTR inhibitor, inhibited fluid accumulation. Taken
      together, these results indicate that hemolysin activates PGE2 production via COX
      2 and that PGE2 stimulates cAMP production. cAMP then activates PKA, which in
      turn stimulates CFTR Cl- channels and finally leads to fluid accumulation in the
      intestines.

PMID- 18086812
TI  - Physical linkage of naturally complexed bacterial outer membrane proteins
      enhances immunogenicity.
AB  - The outer membrane proteins (OMPs) of bacterial pathogens are essential for their
      growth and survival and especially for attachment and invasion of host cells.
      Since the outer membrane is the interface between the bacterium and the host
      cell, outer membranes and individual OMPs are targeted for development of
      vaccines against many bacterial diseases. Whole outer membrane fractions often
      protect against disease, and this protection cannot be fully reproduced by using
      individual OMPs. Exactly how the interactions among individual OMPs influence
      immunity is not well understood. We hypothesized that one OMP rich in T-cell
      epitopes can act as a carrier for an associated OMP which is poor in T-cell
      epitopes to generate T-dependent antibody responses, similar to the hapten
      carrier effect. Major surface protein 1a (MSP1a) and MSP1b1 occur as naturally
      complexed OMPs in the Anaplasma marginale outer membrane. Previous studies
      demonstrated that immunization with the native MSP1 heteromer induced strong
      immunoglobulin G (IgG) responses to both proteins, but only MSP1a stimulated
      strong CD4+ T-cell responses. Therefore, to test our hypothesis, constructs of
      CD4+ T-cell epitopes from MSP1a linked to MSP1b1 were compared with individually
      administered MSP1a and MSP1b1 for induction of MSP1b-specific IgG. By linking the
      T-cell epitopes from MSP1a to MSP1b1, significantly higher IgG titers against
      MSP1b1 were induced. Understanding how the naturally occurring intermolecular
      interactions between OMPs influence the immune response may lead to more
      effective vaccine design.

PMID- 18086813
TI  - Comparison of the effects of Leishmania major or Leishmania donovani infection on
      macrophage gene expression.
AB  - The intracellular parasite Leishmania causes a wide spectrum of human disease,
      ranging from self-resolving cutaneous lesions to fatal visceral disease,
      depending on the species of Leishmania involved. The mechanisms by which
      different Leishmania species cause different pathologies are largely unknown. We
      have addressed this question by comparing the gene expression profiles of bone
      marrow-derived macrophages infected with either Leishmania donovani or L. major
      promastigotes. We found that the two species had very similar effects on
      macrophage gene expression. Both species caused a small (<2.5-fold) but
      statistically significant repression of several hundred genes. In addition, both
      species strongly induced and repressed about 60 genes. Comparing the effects of
      the two species showed that only 26 genes were regulated differently by L. major
      as opposed to L. donovani, including those for metallothioneins 1 and 2, HSP70
      and -72, CCL4, Gadd45beta, Dsp1, matrix metalloprotease 13, T-cell death
      associated gene 51 (Tdag51), RhoB, spermine/spermidine N1-acyl transferase 1
      (SSAT), and Cox2. L. donovani-infected macrophages were also found to express
      higher levels of Cox2 protein and prostaglandin E synthase mRNA than L. major
      infected macrophages. While both species have previously been shown to trigger
      prostaglandin E synthesis by bystander cells, this study suggests that infected
      macrophages themselves express prostaglandin E-synthesizing genes only in
      response to L. donovani.

PMID- 18086815
TI  - Peyer's patches are required for intestinal immunoglobulin A responses to
      Salmonella spp.
AB  - Previous studies have shown that Peyer's patches (PP) are not required for
      intestinal immunoglobulin A (IgA) responses to orally administered soluble
      protein. However, the roles of PP in regulation of mucosal immune responses
      against bacterial antigen remain to be clarified. In the present study, we
      generated several gut-associated lymphoreticular tissue-null mice by treatment
      with anti-interleukin-7 receptor antibody, the fusion protein of lymphotoxin beta
      receptor and IgG Fc, and/or tumor necrosis factor receptor p55 and IgG Fc. These
      mice were then immunized with recombinant Salmonella expressing the C fragment of
      the tetanus toxin (rSalmonella-Tox C). Orally immunized PP-null mice as well as
      isolated lymphoid follicle (ILF)-null, PP/ILF-null, and PP/ILF/mesenteric lymph
      node-null mice induced identical levels of tetanus toxoid (TT)-specific systemic
      IgG responses to those of control mice. However, PP-null mice, but not ILF-null
      mice, failed to induce TT-specific intestinal IgA antibodies. Analysis of TT
      specific CD4+ T-cell responses showed a reduction of gamma interferon (IFN-gamma)
      synthesis in the intestinal lamina propriae of PP-null mice given oral
      rSalmonella-Tox C. In contrast, TT-specific IFN-gamma responses in the spleen and
      delayed-type hypersensitivity responses were intact in those immunized mice.
      Interestingly, Salmonella lipopolysaccharide (LPS)-specific fecal IgA responses
      were not elicited in PP-null mice, while serum IgG anti-LPS antibodies were
      identical to those of control mice. These results suggest that while none of the
      gut-associated lymphoreticular tissues are required for the induction of systemic
      immune responses, PP are an essential lymphoid tissue for induction and
      regulation of intestinal IgA immunity against orally administered rSalmonella.

PMID- 18086814
TI  - Characterization of two putative cytochrome c peroxidases of Campylobacter jejuni
      involved in promoting commensal colonization of poultry.
AB  - Campylobacter jejuni is a leading cause of bacterial gastroenteritis in humans
      throughout the world, but infection of animals, especially poultry, results in a
      commensal colonization of the intestines. We previously found that a mutant
      lacking docA, which encodes a putative cytochrome c peroxidase (CCP),
      demonstrates up to a 10(5)-fold reduction in colonization of the chick cecum
      compared to wild-type C. jejuni strain 81-176. Predictions from genomic sequences
      identified CJJ0382 as a second locus in C. jejuni encoding a CCP, making the
      bacterium unusual in having two putative CCPs. To understand what advantages are
      imparted by having two putative CCPs, we compared the colonization requirements
      of C. jejuni mutants lacking DocA or Cjj0382. Unlike the DeltadocA mutant, a
      DeltaCJJ0382 mutant demonstrates a maximal 50-fold colonization defect that is
      dependent on the inoculum dose. The colonization differences of mutants lacking
      DocA or Cjj0382 suggest that the two predicted CCPs are unlikely to perform
      redundant functions during in vivo growth. In the characterizations of DocA and
      Cjj0382, we found that they are stable periplasmic proteins with an apparent heme
      dependent peroxidase activity, which are characteristics of bacterial CCPs.
      However, the peroxidase activities of the proteins do not appear to contribute to
      resistance to hydrogen peroxide. Instead, we found that resistance to hydrogen
      peroxide in C. jejuni is mostly attributed to the cytoplasmic catalase KatA. Our
      data suggest that DocA and Cjj0382 have characteristics of CCPs but likely
      perform different physiological functions for the bacterium in colonization that
      are not related to resisting oxidative stress.

PMID- 18086816
TI  - Intracellular interleukin-1alpha mediates interleukin-8 production induced by
      Chlamydia trachomatis infection via a mechanism independent of type I interleukin
      1 receptor.
AB  - Chlamydia trachomatis infection induces a wide array of inflammatory cytokines
      and chemokines, which may contribute to chlamydia-induced pathologies. However,
      the precise mechanisms by which Chlamydia induces cytokines remain unclear. Here
      we demonstrate that the proinflammatory cytokine interleukin-1alpha (IL-1alpha)
      plays an essential role in chlamydial induction of the chemokine IL-8. Cells
      deficient in IL-1alpha expression or IL-1alpha-competent cells treated with IL
      1alpha-specific small interfering RNA failed to produce IL-8 in response to
      chlamydial infection. However, neutralization of extracellular IL-1alpha or
      blockade of or deficiency in type I IL-1 receptor (IL-1RI) signaling did not
      affect chlamydial induction of IL-8 in cells capable of producing IL-1alpha.
      These results suggest that IL-1alpha can mediate the chlamydial induction of IL-8
      via an intracellular mechanism independent of IL-1RI, especially during the early
      stage of the infection cycle. This conclusion is further supported by the
      observations that expression of a transgene-encoded full-length IL-1alpha fusion
      protein in the nuclei enhanced IL-8 production and that nuclear localization of
      chlamydia-induced precursor IL-1alpha correlated with chlamydial induction of IL
      8. Thus, we have identified a novel mechanism for chlamydial induction of the
      chemokine IL-8.

PMID- 18086817
TI  - Recognition of bacterial surface polysaccharides by lectins of the innate immune
      system and its contribution to defense against infection: the case of pulmonary
      pathogens.

PMID- 18086819
TI  - Cancer of the nasal cavity in the pediatric population.
AB  - OBJECTIVE: The purpose of this work was to investigate the clinical
      manifestations and diagnostic range of malignant entities presenting as a nasal
      mass in the pediatric population. PATIENTS AND METHODS: A retrospective cohort
      analysis was conducted at a specialty hospital and a tertiary care university
      hospital. Patients aged between birth and 18 years and diagnosed with a
      malignancy that arose within the nasal cavity between the years 1991 and 2006
      were included. This institution-specific patient group was compared with a
      similar cohort of patients extracted from the national Surveillance Epidemiology
      and End Results database. The main outcome measures were the incidence,
      presentation, and diagnoses of nasal cancer presenting in this population.
      RESULTS: Sixteen patients with nasal malignancies presented institutionally in
      the defined pediatric age group. Patient age at the time of diagnosis ranged from
      7 months to 17 years, with a slight male predominance. The main presenting
      symptoms were unilateral nasal congestion and ophthalmologic complaints. The
      median time from presentation to diagnosis was 7 weeks; patients who presented
      with nonspecific complaints, such as nasal obstruction, headache, and fatigue,
      were given a diagnosis, on average, later than those who presented with focal
      manifestations. Nationwide, 47 patients were identified from the Surveillance
      Epidemiology and End Results database. In both subject groups, the most common
      diagnoses were rhabdomyosarcoma (37.5% institutionally and 23% in the
      Surveillance Epidemiology and End Results group) and esthesioneuroblastoma (25%
      institutionally and 28% Surveillance Epidemiology and End Results). In the
      Surveillance Epidemiology and End Results cohort, the overall mean survival rate
      was 188 months. CONCLUSIONS: Nasal cancer in the pediatric population often
      presents with nonspecific signs and symptoms, and a high index of suspicion is
      necessary for a timely diagnosis. Soft tissue sarcomas are expectedly common. The
      relative high frequency of esthesioneuroblastoma is particularly noteworthy.

PMID- 18086818
TI  - Sensing gram-negative bacterial lipopolysaccharides: a human disease determinant?

PMID- 18086820
TI  - Primary varicella and herpes zoster among HIV-infected children from 1989 to
      2006.
AB  - OBJECTIVES: The primary objective of this study was to determine the incidence of
      herpes zoster in perinatally HIV-infected children. Secondary objectives included
      assessing the impact of highly active antiretroviral therapy and varicella zoster
      virus immunization on primary varicella and herpes zoster incidence and
      identifying risk factors for herpes zoster. We hypothesized that the incidence of
      herpes zoster has decreased in this population as a result of highly active
      antiretroviral therapy and routine varicella zoster virus immunization. PATIENTS
      AND METHODS: This retrospective cohort study included HIV-infected children at a
      pediatric HIV clinic from 1989 to 2006. Incidence rates for 3 intervals (1989
      1996, 1997-1999, and 2000-2006) were compared on the basis of introduction of
      highly active antiretroviral therapy (1996) and varicella zoster virus
      vaccination (1999). A Cox proportional-hazards regression model was developed for
      the time to herpes zoster among the subset of patients with primary varicella
      infection. RESULTS: In 356 patients followed for 1721 person-years, the incidence
      of herpes zoster according to period was 30.0 per 1000 person-years in 1989-1996,
      31.9 per 1000 person-years in 1997-1999, and 6.5 per 1000 person-years in 2000
      2006. There was no difference in incidence-rate ratio between 1989-1996 and 1997
      1999. However, there was a significant difference in herpes zoster incidence when
      comparing 1989-1999 with 2000-2006. The incidence of primary varicella zoster
      virus infection and herpes zoster in the 57 patients who received the varicella
      zoster virus vaccine was 22.3 per 1000 and 4.5 per 1000 person-years,
      respectively. Highly active antiretroviral therapy at the time of primary
      varicella zoster virus infection was protective against herpes zoster and
      increased herpes zoster-free survival. CONCLUSIONS: The incidence of herpes
      zoster has decreased since 1989. The decline occurred after 2000, likely
      representing the combined effect of immunization and highly active antiretroviral
      therapy. The use of highly active antiretroviral therapy at the time of primary
      varicella zoster virus infection decreased the risk of herpes zoster and
      increased herpes zoster-free survival. Varicella zoster virus immunization was
      effective in preventing both primary varicella zoster virus and herpes zoster in
      this cohort.

PMID- 18086822
TI  - Dialysis or not? A comparative survival study of patients over 75 years of age
      with chronic kidney disease stage 5.

PMID- 18086821
TI  - Fishing for lectins from diverse sequence libraries by yeast surface display - an
      exploratory study.
AB  - The establishment of a robust technology platform for the expression cloning of
      carbohydrate-binding proteins remains a key challenge in glycomics. Here we
      explore the utility of using yeast surface display (YSD) technology in the
      interaction-based lectin cloning from complete cDNA libraries. This should pave
      the way for more detailed studies of protein-carbohydrate interactions. To
      evaluate the performance of this system, lectins representing three different
      subfamilies (galectins, siglecs, and C-type lectins) were successfully displayed
      on the surface of Saccharomyces cerevisiae and Pichia pastoris as a-agglutinin
      and/or alpha-agglutinin fusions. The predicted carbohydrate-binding activity
      could be detected for three out of five lectins tested (galectin-1, galectin-3,
      and siaoadhesin). For galectin-4 and E-selectin, no specific carbohydrate-binding
      activity could be detected. We also demonstrate that proteins with carbohydrate
      affinity can be specifically isolated from complex metazoan cDNA libraries
      through multiple rounds of FACS sorting, employing multivalent, fluorescent
      labeled polyacrylamide-based glycoconjugates.

PMID- 18086823
TI  - About CKD stage-3 subdivision proposal.

PMID- 18086824
TI  - Differential regional expression of brain-derived neurotrophic factor following
      olfactory fear learning.
AB  - We examined brain-derived neurotrophic factor (BDNF) mRNA expression across the
      olfactory system following fear conditioning. Mice received 10 pairings of odor
      with footshock or equivalent unpaired odors and shocks. We found increased BDNF
      mRNA in animals receiving paired footshocks in the multiple regions examined
      including the posterior piriform cortex (PPC) and basolateral amygdala (BLA).
      This was in contrast to the unpaired and odor-alone treatments, where BDNF mRNA
      was increased in the olfactory bulb (OB) and anterior piriform cortex (APC) only,
      but not the higher olfactory areas. We propose that odor exposure increases
      expression of BDNF in the OB and APC while the PPC and BLA increase BDNF mRNA
      only when associative learning occurs.

PMID- 18086825
TI  - Perirhinal cortex resolves feature ambiguity in configural object recognition and
      perceptual oddity tasks.
AB  - The perirhinal cortex (PRh) has a well-established role in object recognition
      memory. More recent studies suggest that PRh is also important for two-choice
      visual discrimination tasks. Specifically, it has been suggested that PRh
      contains conjunctive representations that help resolve feature ambiguity, which
      occurs when a task cannot easily be solved on the basis of features alone.
      However, no study has examined whether the ability of PRh to resolve configural
      feature ambiguity is related to its role in object recognition. Therefore, we
      examined whether bilateral excitotoxic lesions of PRh or PPRh (perirhinal plus
      post-rhinal cortices) in the rat would cause deficits in a configural spontaneous
      object recognition task, and a configural simultaneous oddity discrimination
      task, in which the task could not be solved on the basis of features, but could
      only be solved using conjunctive representations. As predicted by simulations
      using a computational model, rats with PPRh lesions were impaired during a
      minimal-delay configural object recognition task. These same rats were impaired
      during a zero-delay configural object recognition task. Furthermore, rats with
      localized PRh lesions were impaired in a configural simultaneous oddity
      discrimination task. These findings support the idea that PRh contains
      conjunctive representations for the resolution of feature ambiguity and that
      these representations underlie a dual role for PRh in memory and perception.

PMID- 18086827
TI  - Inferior colliculus lesions impair eyeblink conditioning in rats.
AB  - The neural plasticity necessary for acquisition and retention of eyeblink
      conditioning has been localized to the cerebellum. However, the sources of
      sensory input to the cerebellum that are necessary for establishing learning
      related plasticity have not been identified completely. The inferior colliculus
      may be a source of sensory input to the cerebellum through its projection to the
      medial auditory thalamus. The medial auditory thalamus is necessary for eyeblink
      conditioning in rats and projects to the lateral pontine nuclei, which then
      project to the cerebellar nuclei and cortex. The current experiment examined the
      role of the inferior colliculus in auditory eyeblink conditioning. Rats were
      given bilateral or unilateral (contralateral to the conditioned eye) lesions of
      the inferior colliculus prior to 10 d of delay eyeblink conditioning with a tone
      CS. Rats with bilateral or unilateral lesions showed equivalently impaired
      acquisition. The extent of damage to the contralateral inferior colliculus
      correlated with several measures of conditioning. The findings indicate that the
      contralateral inferior colliculus provides auditory input to the cerebellum that
      is necessary for eyeblink conditioning.

PMID- 18086826
TI  - The memory-impairing effects of septal GABA receptor activation involve GABAergic
      septo-hippocampal projection neurons.
AB  - Septal infusions of the gamma-aminobutyric acid (GABA)(A) agonist muscimol impair
      memory, and the effect likely involves the hippocampus. GABA(A) receptors are
      present on the perikarya of cholinergic and GABAergic septo-hippocampal (SH)
      projections. The current experiments determined whether GABAergic SH projections
      are involved in the memory-impairing effects of septal GABA(A) receptor
      activation. Experiment 1 tested whether combining septal co-infusions of
      subeffective doses of muscimol with scopolamine, a drug that selectively
      influences GABA SH projections, would produce memory deficits. Experiment 2
      tested whether hippocampal infusions of a GABA(A) receptor antagonist would block
      the effects of septal muscimol infusions. Fifteen minutes prior to assessing
      spontaneous alternation (SA) or training in a multiple trial inhibitory avoidance
      (CMIA) task, male Sprague-Dawley rats were given septal infusions of vehicle,
      muscimol, scopolamine, or co-infusions of muscimol with scopolamine, or septal
      infusions of vehicle or muscimol combined with hippocampal infusions of vehicle
      or bicuculline. Septal co-infusions of muscimol with scopolamine significantly
      impaired SA and CMIA. Hippocampal bicuculline infusions blocked deficits produced
      by septal muscimol infusions in SA and attenuated deficits produced in CMIA.
      Combined, these findings suggest that GABAergic SH projections are involved in
      the memory-impairing effects of septal GABA receptor activation.

PMID- 18086828
TI  - Noradrenergic control of odor recognition in a nonassociative olfactory learning
      task in the mouse.
AB  - The present study examined the influence of pharmacological modulations of the
      locus coeruleus noradrenergic system on odor recognition in the mouse. Mice
      exposed to a nonrewarded olfactory stimulation (training) were able to memorize
      this odor and to discriminate it from a new odor in a recall test performed 15
      min later. At longer delays (30 or 60 min), the familiar odor was no longer
      retained, and both stimuli were perceived as new ones. Following a post-training
      injection of the alpha(2)-adrenoceptor antagonist dexefaroxan, the familiar odor
      was still remembered 30 min after training. In contrast, both the alpha(2)
      adrenoceptor agonist UK 14304 and the noradrenergic neurotoxin DSP-4 prevented
      the recognition of the familiar odor 15 min after the first exposure.
      Noradrenaline release in the olfactory bulb, assessed by measurement of the
      extracellular noradrenaline metabolite normetanephrine, was increased by 62%
      following dexefaroxan injection, and was decreased by 38%-44% after treatment
      with UK 14304 and DSP-4. Performance of mice in the recall test was reduced by a
      post-training injection of the beta-adrenoceptor antagonist propranolol or the
      alpha(1)-antagonist prazosin, thus implicating a role for beta- and alpha(1)
      adrenoceptors in the facilitating effects of noradrenaline on short-term
      olfactory recognition in this model.

PMID- 18086829
TI  - The role of the nucleus basalis magnocellularis in fear conditioning
      consolidation in the rat.
AB  - The nucleus basalis magnocellularis (NBM) is known to be involved in the
      memorization of several conditioned responses. To investigate the role of the NBM
      in fear conditioning memorization, this neural site was subjected to fully
      reversible tetrodotoxin (TTX) inactivation during consolidation in adult male
      Wistar rats that had undergone fear training to acoustic conditioned stimulus
      (CS) and context. TTX was stereotaxically administered to different groups of
      rats at increasing intervals after the acquisition session. Memory was assessed
      as the conditioned freezing duration measured during retention testing, always
      performed 72 and 96 h after TTX administration. In this way, there was no
      interference with normal NBM function during either acquisition or retrieval
      phases, allowing any amnesic effect to be due only to consolidation disruption.
      The results show that for contextual fear response memory consolidation, NBM
      functional integrity is necessary up to 24 h post-acquisition. On the other hand,
      NBM functional integrity was shown to be necessary for memory consolidation of
      the acoustic CS fear response only immediately after acquisition and not 24-h
      post-acquisition. The present findings help to elucidate the role of the NBM in
      memory consolidation and better define the neural circuits involved in fear
      memories.

PMID- 18086830
TI  - Stress administered prior to encoding impairs neutral but enhances emotional long
      term episodic memories.
AB  - Stressful events frequently comprise both neutral and emotionally arousing
      information, yet the impact of stress on emotional and neutral events is still
      not fully understood. The hippocampus and frontal cortex have dense
      concentrations of receptors for stress hormones, such as cortisol, which at high
      levels can impair performance on hippocampally dependent memory tasks. Yet, the
      same stress hormones can facilitate memory for emotional information, which
      involves interactions between the hippocampus and amygdala. Here, we induced
      psychosocial stress prior to encoding and examined its long-term effects on
      memory for emotional and neutral episodes. The stress manipulation disrupted long
      term memory for a neutral episode, but facilitated long-term memory for an
      equivalent emotional episode compared with a control condition. The stress
      manipulation also increased salivary cortisol, catecholamines as indicated by the
      presence of alpha-amylase, heart rate, and subjectively reported stress. Stressed
      subjects reported more false memories than nonstressed control subjects, and
      these false memories correlated positively with cortisol levels, providing
      evidence for a relationship between stress and false memory formation. Our
      results demonstrate that stress, when administered prior to encoding, produces
      different patterns of long-term remembering for neutral and emotional episodes.
      These differences likely emerge from differential actions of stress hormones on
      memory-relevant regions of the brain.

PMID- 18086831
TI  - Aryl-propionamide-derived selective androgen receptor modulators: liquid
      chromatography-tandem mass spectrometry characterization of the in vitro
      synthesized metabolites for doping control purposes.
AB  - Selective androgen receptor modulators (SARM) are a prominent group of compounds
      for being misused in sports owing to their advantageous anabolic properties and
      reduced side effects. To target the preventive doping control analysis in
      relevant compounds, the challenge is to predict the metabolic fate of a new
      compound. For aryl-propionamide-derived SARM, an in vitro assay employing
      microsomal and S9 human liver enzymes was developed to simulate phase-I and phase
      II metabolic reactions. In vitro metabolic profiles and the structure-metabolic
      relationship were compared between four structurally modified substrates.
      Accurate mass measurements were used to characterize the synthesized metabolites,
      and also collision-induced dissociation was examined to suggest the
      methodological approach to monitor the prohibited use of aryl-propionamide
      derived drug candidates. Subsequent phase-I and phase-II metabolic reactions were
      successfully combined in one in vitro assay. The main routes of phase-I
      modifications involved the hydrolysis of ether linkage, monohydroxylation, and
      hydrolytic cleavage of the amide bond. Nitro-reduction and deacetylation were
      reactions observed for substrates possessing the corresponding functionality.
      SARM metabolites were analyzed in negative ion electrospray ionization and
      detected as deprotonated species [M-H](-). The main metabolic modifications were
      observed to occur in the B-ring side, and collision-induced dissociation resulted
      in the product ions originating from the A-ring side of the compound. These
      structure-specific ions may be monitored as target ions in the routine doping
      control.

PMID- 18086832
TI  - Regulation of aryl hydrocarbon receptor expression and function by
      glucocorticoids in mouse hepatoma cells.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      that mediates most biological responses to 2,3, 7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) and related aromatic hydrocarbons. Although the role of the AHR in control
      of drug metabolism and endocrine disruption is partly understood, we know little
      about the regulation of the AHR itself by endocrine factors. Our work with
      hypophysectomized rats suggested that hepatic AHR protein level is positively
      regulated by pituitary-dependent factors. A current hypothesis is that adrenal
      glucocorticoids elevate AHR expression and enhance responsiveness to AHR
      agonists. Dexamethasone (DEX) at concentrations that activate the glucocorticoid
      receptor (GR) increased AHR mRNA, protein, and TCDD-binding by approximately 50%
      in Hepa-1 mouse hepatoma cells. This response was blocked by the GR antagonist
      17beta-hydroxy-11beta-[4-dimethylamino phenyl]-17alpha-[1-propynyl]estra-4,9-dien
      3-one (RU486), suggesting GR involvement. This small magnitude increase in AHR
      levels was functionally significant; pretreatment of Hepa-1 cells with DEX caused
      a 75% increase in the maximum induction of an AHR-activated luciferase reporter
      plasmid by TCDD. A luciferase reporter under control of the proximal 2.5
      kilobases of the mouse Ahr 5'-flanking region and promoter was induced
      approximately 2.5-fold by DEX when cotransfected with a mouse GR expression
      plasmid. This is the first demonstration that glucocorticoids increase AHR levels
      in hepatoma cells via a GR-dependent transcriptional mechanism, suggesting a
      novel aspect of cross-talk between the AHR and the GR.

PMID- 18086833
TI  - Novel variant of the qnrB gene, qnrB12, in Citrobacter werkmanii.

PMID- 18086834
TI  - Induction of erm(C) expression by noninducing antibiotics.
AB  - Ketolides, which represent the newest macrolide antibiotics, are generally
      perceived to be noninducers of inducible erm genes. In the study described in
      this paper we investigated the effects of several macrolide and ketolide
      compounds on the expression of the inducible erm(C) gene by Escherichia coli
      cells. Exposure to 14-member-ring macrolide drugs and to azithromycin led to a
      rapid and pronounced increase in the extent of dimethylation of Erm(C) target
      residue A2058 in 23S rRNA. When cells were incubated with subinhibitory
      concentrations of ketolides, the extent of A2058 dimethylation was also
      increased, albeit to a lower level and with kinetics slower than those observed
      with macrolides. The induction of erm(C) expression by ketolides was further
      confirmed by using a reporter construct which allows the colorimetric detection
      of induction in a disc diffusion assay. Most of the ketolides tested, including
      the clinically relevant compounds telithromycin and cethromycin, were able to
      induce the reporter expression, even though the induction occurred within a more
      narrow range of concentrations compared to the concentration range at which
      induction was achieved with the inducing macrolide antibiotics. No induction of
      the reporter expression was observed with 16-member-ring macrolide antibiotics or
      with a control drug, chloramphenicol. The deletion of three codons of the erm(C)
      leader peptide eliminated macrolide-dependent induction but left ketolide
      dependent induction unchanged. We conclude that ketolides are generally capable
      of inducing erm genes. The narrow range of ketolide inducing concentrations,
      coupled with the slow rate of induction and the lower steady-state level of
      ribosome methylation, may mask this effect in MIC assays.

PMID- 18086835
TI  - Dectin-1 Fc targeting of aspergillus fumigatus beta-glucans augments innate
      defense against invasive pulmonary aspergillosis.
AB  - Invasive pulmonary aspergillosis (IPA) has significantly increased over the last
      decade. Here, a fusion protein consisting of the Dectin-1 extracellular domain
      linked to the Fc portion of murine immunoglobulin G1 augmented alveolar
      macrophage killing of Aspergillus fumigatus and shifted mortality associated with
      IPA via attenuation of A. fumigatus growth in the lung.

PMID- 18086836
TI  - Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among
      hospitalized adults and effect of acquisition on mortality.
AB  - Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging nosocomial
      pathogen. Little is known about its risk factors or mortality. We performed a
      case-case-control study to assess the risks for CRKP isolation and a
      retrospective cohort study to assess mortality in three groups of hospitalized
      adults: (i) patients from whom CRKP was isolated, (ii) patients from whom
      carbapenem-susceptible Klebsiella spp. (CSKS) were isolated, and (iii) controls
      from whom no Klebsiella spp. were isolated. After adjustment for length of stay
      (LOS), the demographics, comorbidities, and exposures of each case group were
      compared with those of the controls. Significant covariates were incorporated
      into LOS-adjusted multivariable models. In the mortality study, we evaluated the
      effect of CRKP on in-hospital death. There were 48 patients with CRKP isolation
      (21 died [44%]), 56 patients with CSKS isolation (7 died [12.5%]), and 59
      controls (1 died [2%]). Independent risk factors for CRKP isolation were poor
      functional status (odds ratio [OR], 15.4; 95% confidence interval [CI], 4.0 to
      58.6; P < 0.001); intensive care unit (ICU) stay (OR, 17.4; 95% CI, 1.5 to 201.9;
      P = 0.02); and receipt of antibiotics (OR, 4.4; 95% CI, 1.0 to 19.2; P = 0.05),
      particularly fluoroquinolones (OR, 7.2; 95% CI, 1.1 to 49.4; P = 0.04). CRKP was
      independently associated with death when patients with CRKP were compared with
      patients with CSKS (OR, 5.4; 95% CI, 1.7 to 17.1; P = 0.005) and with controls
      (OR, 6.7; 95% CI, 2.4 to 18.8; P < 0.001). After adjustment for the severity of
      illness, CRKP isolation remained predictive of death, albeit with a lower OR (for
      the CRKP group versus the CSKS group, OR, 3.9; 95% CI, 1.1 to 13.6; and P = 0.03;
      for the CRKP group versus the controls, OR, 5.0; 95% CI, 1.7 to 14.8; and P =
      0.004). CRKP affects patients with poor functional status, an ICU stay, and
      antibiotic exposure and is an independent predictor of death.

PMID- 18086837
TI  - Emergence of antibiotic resistance during therapy for infections caused by
      Enterobacteriaceae producing AmpC beta-lactamase: implications for antibiotic
      use.
AB  - Enterobacter spp., Serratia marcescens, Citrobacter freundii, and Morganella
      morganii are characterized by chromosomally encoded AmpC beta-lactamases and
      possess the ability to develop resistance upon exposure to broad-spectrum
      cephalosporins. To determine the incidences of the emergence of resistance during
      antimicrobial therapy for infections caused by these organisms and the effect of
      the emergence of resistance on patient outcomes, all patients who were admitted
      to the Asan Medical Center (Seoul, Republic of Korea) from January 2005 to June
      2006 and whose clinical specimens yielded Enterobacter spp., S. marcescens, C.
      freundii, or M. morganii were monitored prospectively. The main end point was the
      emergence of resistance during antimicrobial therapy. A total of 732 patients
      with infections were included for analysis. The overall incidence of the
      emergence of antimicrobial resistance during antimicrobial therapy was 1.9%
      (14/732). Resistance to broad-spectrum cephalosporins, cefepime, extended
      spectrum penicillin, carbapenem, fluoroquinolones, and aminoglycosides emerged
      during treatment in 5.0% (11/218), 0% (0/20), 2.0% (2/100), 0% (0/226), 0%
      (0/153), and 1.1% (1/89) of patients, respectively. The emergence of resistance
      to broad-spectrum cephalosporins occurred more often in Enterobacter spp. (8.3%,
      10/121) than in C. freundii (2.6%, 1/39), S. marcescens (0%, 0/37), or M.
      morganii (0%, 0/21). Biliary tract infection associated with malignant bile duct
      invasion was significantly associated with the emergence of resistance to broad
      spectrum cephalosporins (P = 0.024 at a significance level of 0.042, by use of
      the Bonferroni correction). Only 1 of the 14 patients whose isolates developed
      resistance during antimicrobial therapy died. The emergence of resistance was
      more frequently associated with broad-spectrum cephalosporins than with the other
      antimicrobial agents tested, especially in Enterobacter spp. However, the
      emergence of resistance was associated with a low risk of mortality.

PMID- 18086838
TI  - Increases in SLT2 expression and chitin content are associated with incomplete
      killing of Candida glabrata by caspofungin.
AB  - Incomplete killing was observed for caspofungin against Candida glabrata, which
      was associated with increased SLT2 expression and elevated chitin content. In
      contrast, fungicidal activity and no chitin increase were observed in an isogenic
      Delta slt2 strain, suggesting a role for SLT2 and chitin production in the
      response of C. glabrata to caspofungin.

PMID- 18086839
TI  - Isolation and purification of enterocin E-760 with broad antimicrobial activity
      against gram-positive and gram-negative bacteria.
AB  - Strain NRRL B-30745, isolated from chicken ceca and identified as Enterococcus
      durans, Enterococcus faecium, or Enterococcus hirae, was initially identified as
      antagonistic to Campylobacter jejuni. The isolate produced a 5,362-Da bacteriocin
      (enterocin) that inhibits the growth of Salmonella enterica serovar Enteritidis,
      S. enterica serovar Choleraesuis, S. enterica serovar Typhimurium, S. enterica
      serovar Gallinarum, Escherichia coli O157:H7, Yersinia enterocolitica,
      Citrobacter freundii, Klebsiella pneumoniae, Shigella dysenteriae, Pseudomonas
      aeruginosa, Proteus mirabilis, Morganella morganii, Staphylococcus aureus,
      Staphylococcus epidermidis, Listeria monocytogenes, Campylobacter jejuni, and 20
      other Campylobacter species isolates. The enterocin, E-760, was isolated and
      purified by cation-exchange and hydrophobic-interaction chromatographies. The
      proteinaceous nature of purified enterocin E-760 was demonstrated upon treatment
      with various proteolytic enzymes. Specifically, the antimicrobial peptide was
      found to be sensitive to beta-chymotrypsin, proteinase K, and papain, while it
      was resistant to lysozyme and lipase. The enterocin demonstrated thermostability
      by retaining activity after 5 min at 100 degrees C and was stable at pH values
      between 5.0 and 8.7. However, activity was lost below pH 3.0 and above pH 9.5.
      Administration of enterocin E-760-treated feed significantly (P < 0.05) reduced
      the colonization of young broiler chicks experimentally challenged and colonized
      with two strains of C. jejuni by more than 8 log(10) CFU. Enterocin E-760 also
      significantly (P < 0.05) reduced the colonization of naturally acquired
      Campylobacter species in market age broiler chickens when administered in treated
      feed 4 days prior to analysis.

PMID- 18086841
TI  - The mitochondrion is a site of trypanocidal action of the aromatic diamidine DB75
      in bloodstream forms of Trypanosoma brucei.
AB  - Human African trypanosomiasis (HAT) is a fatal tropical disease caused by
      infection with protozoans of the species Trypanosoma brucei gambiense and T. b.
      rhodesiense. An oral prodrug, DB289, is a promising new therapy undergoing phase
      III clinical trials for early-stage HAT. DB289 is metabolically converted to the
      active trypanocidal diamidine DB75 [2,5-bis(4-amidinophenyl)furan]. We previously
      determined that DB75 inhibits yeast mitochondrial function (C. A. Lanteri, B. L.
      Trumpower, R. R. Tidwell, and S. R. Meshnick, Antimicrob. Agent Chemother.
      48:3968-3974, 2004). The purpose of this study was to investigate if DB75 targets
      the mitochondrion of T. b. brucei bloodstream forms. DB75 rapidly accumulates
      within the mitochondria of living trypanosomes, as indicated by the fluorescent
      colocalization of DB75 with a mitochondrion-specific dye. Fluorescence-activated
      cell sorting analysis of rhodamine 123-stained living trypanosomes shows that
      DB75 and other trypanocidal diamidines (pentamidine and diminazene) collapse the
      mitochondrial membrane potential. DB75 inhibits ATP hydrolysis within T. brucei
      mitochondria and appears to inhibit the oligomycin-sensitive F 1 F 0-ATPase and
      perhaps other ATPases. DB75 is most likely not an inhibitor of electron transport
      within trypanosome mitochondria, since DB75 fails to inhibit mitochondrial
      respiration when glycerol-3-phosphate is used as the respiratory substrate.
      However, DB75 inhibits whole-cell respiration (50% inhibitory concentration, 20
      microM) at drug concentrations and incubation durations that also result in the
      dissipation of the mitochondrial membrane potential. Taken together, these
      findings suggest that the mitochondrion is a target of the trypanocidal action of
      DB75.

PMID- 18086840
TI  - Human macrophage inflammatory protein 3alpha: protein and peptide nuclear
      magnetic resonance solution structures, dimerization, dynamics, and anti
      infective properties.
AB  - Human macrophage inflammatory protein 3alpha (MIP-3alpha), also known as CCL20,
      is a 70-amino-acid chemokine which exclusively binds to chemokine receptor 6. In
      addition, the protein also has direct antimicrobial, antifungal, and antiviral
      activities. The solution structure of MIP-3alpha was solved by the use of two
      dimensional homonuclear proton nuclear magnetic resonance (NMR). The structure
      reveals the characteristic chemokine fold, with three antiparallel beta strands
      followed by a C-terminal alpha helix. In contrast to the crystal structures of
      MIP-3alpha, the solution structure was found to be monomeric. Another difference
      between the NMR and crystal structures lies in the angle of the alpha helix with
      respect to the beta strands, which measure 69 and approximately 56.5 degrees in
      the two structures, respectively. NMR diffusion and pH titration studies revealed
      a distinct tendency for MIP-3alpha to form dimers at neutral pH and monomers at
      lower pH, dependent on the protonation state of His40. Molecular dynamics
      simulations of both the monomeric and the dimeric forms of MIP-3alpha supported
      the notion that the chemokine undergoes a change in helix angle upon dimerization
      and also highlighted the important hydrophobic and hydrogen bonding contacts made
      by His40 in the dimer interface. Moreover, a constrained N terminus and a smaller
      binding groove were observed in dimeric MIP-3alpha simulations, which could
      explain why monomeric MIP-3alpha may be more adept at receptor binding and
      activation. The solution structure of a synthetic peptide consisting of the last
      20 residues of MIP-3alpha displayed a highly amphipathic alpha helix, reminiscent
      of various antimicrobial peptides. Antimicrobial assays with this peptide
      revealed strong and moderate bactericidal activities against Escherichia coli and
      Staphylococcus aureus, respectively. This confirms that the C-terminal alpha
      helical region of MIP-3alpha plays a significant part in its broad anti-infective
      activity.

PMID- 18086842
TI  - Adsorption of amikacin, a significant mechanism of elimination by hemofiltration.
AB  - We used an in vitro model of continuous venovenous hemofiltration (CVVH) to
      characterize amikacin adsorption by polyacrylonitrile (PAN) and polyamide
      filters. A blood-crystalloid mixture dosed with amikacin was pumped from a
      reservoir through a hemofiltration circuit and back to the reservoir. All
      ultrafiltrate was also returned to the reservoir. The level of adsorption was
      calculated from the fall in the amikacin concentration. The dose and the initial
      concentration of amikacin were varied, as were the pH, the type of hemofilter,
      and the hemofilter surface area. The reversibility of adsorption and the effect
      of repeated dosing were also studied. The level of adsorption by 0.6-m2 PAN
      filters was significantly greater than that by 0.6-m2 polyamide filters.
      Adsorption was increased by increasing the dose of amikacin even when the initial
      concentration was unchanged. It was unaffected by the pH (pH 6.8 or 7.4) or the
      hemofilter surface area (0.6 m2 or 0.9 m2). Repeated doses of amikacin resulted
      in further adsorption. In a saturation experiment, the maximum adsorptive
      capacity of 0.6-m2 PAN hemofilters was at least 546.9 mg (range, 427.6 to 577.5
      mg). The adsorption of amikacin by hemofilters is irreversible and was associated
      with the dose and the hemofilter material but not the hemofilter surface area.
      Close monitoring of peak amikacin levels should be considered for patients
      receiving CVVH with PAN hemofilters.

PMID- 18086843
TI  - Novel characteristics of community-acquired methicillin-resistant Staphylococcus
      aureus strains belonging to multilocus sequence type 59 in Taiwan.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strains,
      which often produce Panton-Valentine leucocidin (PVL), are increasingly noted
      worldwide. In this study, we examined 42 MRSA strains (25 PVL-positive [PVL+]
      strains and 17 PVL-negative [PVL(-)] strains) isolated in Taiwan for their
      molecular characteristics. The PVL+ MRSA strains included CA-MRSA strains with
      multilocus sequence type (ST) 59 (major PVL+ MRSA in Taiwan), its variants, and
      worldwide CA-MRSA ST30 strains. The PVL(-) MRSA strains included the pandemic
      Hungarian MRSA ST239 strain, the Hungarian MRSA ST239 variant, MRSA ST59 (largely
      hospital-acquired MRSA strains) and its variants, the pandemic New York/Japan
      MRSA ST5 strain (Japanese type), and the MRSA ST8 strain. The major PVL+ CA-MRSA
      ST59 strain possessed a tetracycline resistance-conferring (tetK positive)
      penicillinase plasmid and a drug resistance gene cluster (a possible composite
      transposon) for multidrug resistance. Moreover, it carried a novel staphylococcal
      cassette chromosome mec (SCCmec) with two distinct ccrC genes (ccrC2-C8). This
      SCCmec (previously named SCCmec type V(T)) was tentatively designated SCCmec type
      VII. Sequencing of the PVL genes revealed the polymorphisms, and the PVL+ CA-MRSA
      ST59 strain possessed the ST59-specific PVL gene sequence. The data suggest that
      a significant amount of clonal spread is occurring in Taiwan and that the major
      PVL+ CA-MRSA ST59 Taiwan strain exhibits unique genetic characteristics, such as
      a novel SCCmec type and an ST59-specific PVL gene sequence.

PMID- 18086844
TI  - Lincomycin resistance gene lnu(D) in Streptococcus uberis.
AB  - Streptococcus uberis UCN 42, isolated from a case of bovine mastitis, was
      intermediately resistant to lincomycin (MIC = 2 microg/ml) while remaining
      susceptible to clindamycin (MIC = 0.06 microg/ml) and erythromycin. A 1.1-kb SacI
      fragment was cloned from S. uberis UCN 42 total DNA on plasmid pUC 18 and
      introduced into Escherichia coli AG100A, where it conferred resistance to both
      clindamycin and lincomycin. The sequence analysis of the fragment showed the
      presence of a new gene, named lnu(D), that encoded a 164-amino-acid protein with
      53% identity with Lnu(C) previously reported to occur in Streptococcus
      agalactiae. Crude lysates of E. coli AG100A containing the cloned lnu(D) gene
      inactivated lincomycin and clindamycin in the presence of ATP and MgCl(2). Mass
      spectrometry experiments demonstrated that the lnu(D) enzyme catalyzed
      adenylylation of clindamycin. A domain conserved in deduced sequences of
      lincosamide O-nucleotidyltransferases Lnu(A), Lnu(C), LinA(N2), and Lin(D) and in
      the aminoglycoside nucleotidyltransferase ANT(2'') was identified.

PMID- 18086845
TI  - Concentrations of dapivirine in the rhesus macaque and rabbit following once
      daily intravaginal administration of a gel formulation of [14C]dapivirine for 7
      days.
AB  - Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as
      a topical microbicide for the prevention of human immunodeficiency virus
      infection. The distribution of radioactivity and drug in plasma and in vaginal,
      cervical, and draining lymph node tissues was investigated after daily
      application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques.
      This was preceded by a preliminary study with rabbits. Following the intravaginal
      administration of [14C]dapivirine ( approximately 0.1 mg/ml [15 microCi/ml]) to
      rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels
      associated with vaginal and cervical tissue samples 1 h after the final dose were
      high (quantities of microg/g of tissue) and remained detectable at 24 h (mean,
      >or=2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity
      levels were low in the plasma and very low or unquantifiable in the draining
      lymph nodes of the macaques. Microautoradiography identified drug-related
      material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits
      and macaques. Although DRM was primarily associated with the outermost layer of
      shedding cells in rabbits, two animals showed some evidence of small quantities
      in the mucosal epithelium of the cervix. In macaques, DRM was seen within the
      keratinized layer of the vaginal epithelium and and was found to extend into the
      superficial cellular layers, and in at least one animal it appeared to be present
      in the deepest (germinal) layer of the epithelium and in submucosal tissues. The
      persistence of biologically significant concentrations of dapivirine in vaginal
      and cervical tissues for >24 h supports the development of dapivirine as a
      microbicide for once daily application.

PMID- 18086846
TI  - Transcriptional profiling reveals that daptomycin induces the Staphylococcus
      aureus cell wall stress stimulon and genes responsive to membrane depolarization.
AB  - Daptomycin is a lipopeptide antibiotic that has recently been approved for
      treatment of gram-positive bacterial infections. The mode of action of daptomycin
      is not yet entirely clear. To further understand the mechanism transcriptomic
      analysis of changes in gene expression in daptomycin-treated Staphylococcus
      aureus was carried out. The expression profile indicated that cell wall stress
      stimulon member genes (B. J. Wilkinson, A. Muthaiyan, and R. K. Jayaswal, Curr.
      Med. Chem. Anti-Infect. Agents 4:259-276, 2005) were significantly induced by
      daptomycin and by the cell wall-active antibiotics vancomycin and oxacillin.
      Comparison of the daptomycin response of a two-component cell wall stress
      stimulon regulator VraSR mutant, S. aureus KVR, to its parent N315 showed
      diminished expression of the cell wall stress stimulon in the mutant. Daptomycin
      has been proposed to cause membrane depolarization, and the transcriptional
      responses to carbonyl cyanide m-chlorophenylhydrazone (CCCP) and nisin were
      determined. Transcriptional profiles of the responses to these antimicrobial
      agents showed significantly different patterns compared to those of the cell wall
      active antibiotics, including little or no induction of the cell wall stress
      stimulon. However, there were a significant number of genes induced by both CCCP
      and daptomycin that were not induced by oxacillin or vancomycin, so the
      daptomycin transcriptome probably reflected a membrane depolarizing activity of
      this antimicrobial also. The results indicate that inhibition of peptidoglycan
      biosynthesis, either directly or indirectly, and membrane depolarization are
      parts of the mode of action of daptomycin.

PMID- 18086847
TI  - Risk factors for trimethoprim-sulfamethoxazole resistance in patients with acute
      uncomplicated cystitis.
AB  - Emerging antimicrobial resistance among uropathogens makes the management of
      acute uncomplicated cystitis increasingly challenging. Few prospective data are
      available on the risk factors for resistance to trimethoprim-sulfamethoxazole
      (TMP-SMX), the drug of choice in most settings. In order to evaluate this, we
      prospectively enrolled women 18 to 50 years of age presenting to an urban primary
      care practice with symptoms of cystitis. Potentially eligible women provided a
      urine sample for culture and completed a questionnaire regarding putative risk
      factors for TMP-SMX resistance. Escherichia coli isolates were tested for clonal
      group A (CGA) membership by a fumC-specific PCR. Of 165 women with cystitis
      symptoms, 103 had a positive urine culture and were eligible for participation.
      E. coli was the predominant uropathogen (86%). Fifteen (14.6%) women had a TMP
      SMX-resistant (TMP-SMX r) organism (all of which were E. coli). Compared with the
      women who had a TMP-SMX-susceptible organism, women in the TMP-SMX r group were
      more likely to have traveled (odds ratio [OR], 15.4; 95% confidence interval
      [CI], 4.4 to 54.3; P < 0.001) and to be Asian (OR, 6.1; 95% CI, 1.0 to 36.4; P =
      0.048). CGA was also independently associated with TMP-SMX resistance (OR, 105;
      95% CI, 6.3 to 1,777.6; P = 0.001). No association with TMP-SMX resistance was
      demonstrated for the use of either TMP-SMX or another antibiotic in the past 3
      months or with having a child in day care. Among these women with acute
      uncomplicated cystitis, Asian race and recent travel were independently
      associated with TMP-SMX resistance. TMP-SMX r isolates were more likely to belong
      to CGA. Knowledge of these risk factors for TMP-SMX resistance could facilitate
      the accurate selection of empirical therapy.

PMID- 18086848
TI  - Resistance of Porphyromonas gingivalis ATCC 33277 to direct killing by
      antimicrobial peptides is protease independent.
AB  - Antimicrobial peptides are short, positively charged, amphipathic peptides that
      possess a wide spectrum of antimicrobial activity and have an important role in
      the host's innate immunity. Lack of, or dysfunctions in, antimicrobial peptides
      have been correlated with infectious diseases, including periodontitis.
      Porphyromonas gingivalis, a gram-negative anaerobe and a major pathogen
      associated with periodontal diseases, is resistant to antimicrobial peptides of
      human and nonhuman origin, a feature that likely contributes to its virulence.
      Expressing a robust proteolytic activity, P. gingivalis hydrolyzes antimicrobial
      peptides. In this study, P. gingivalis inactivated three antimicrobial peptides,
      while a d-enantiomer was resistant to degradation. P. gingivalis was resistant to
      the protease-resistant d-enantiomer peptide, and importantly, a protease
      deficient P. gingivalis mutant was also resistant to the antimicrobial peptide.
      Finally, the binding of a fluorescently labeled antimicrobial peptide to protease
      deficient P. gingivalis was much weaker than the binding of susceptible
      Escherichia coli. Our results suggest that the resistance of P. gingivalis ATCC
      33277 to direct killing by antimicrobial peptides is protease independent and
      results (at least partially) from the low affinity of antimicrobial peptides to
      P. gingivalis.

PMID- 18086849
TI  - Antimycobacterial Activity and Mechanism of Action of NAS-91.
AB  - The antimalarial agents NAS-91 and NAS-21 were found to express potent
      antimycobacterial activity, NAS-91 being more active than NAS-21. They partially
      inhibited mycolic acid biosynthesis and profoundly altered oleic acid production.
      The development of a cell-free assay for Delta 9-desaturase activity allowed
      direct demonstration of the inhibition of oleic acid biosynthesis by these
      compounds.

PMID- 18086850
TI  - Carbapenem-resistant isolates of Klebsiella pneumoniae in China and detection of
      a conjugative plasmid (blaKPC-2 plus qnrB4) and a blaIMP-4 gene.

PMID- 18086851
TI  - Relative replication capacity and selective advantage profiles of protease
      inhibitor-resistant hepatitis C virus (HCV) NS3 protease mutants in the HCV
      genotype 1b replicon system.
AB  - We characterized the selective advantage profiles of a panel of hepatitis C virus
      (HCV) NS3 protease mutants with three HCV protease inhibitors (PIs), BILN-2061,
      ITMN-191, and VX-950, using a genotype 1b HCV replicon system. Selective
      advantage curves were generated by a novel mathematical method that factors in
      the degree of drug susceptibility provided by the mutation, the base-level
      replication capacity of the mutant in the absence of drugs, and the overall viral
      replication levels as a function of drug concentration. Most of the mutants
      showed significantly increased selective advantages over the wild-type species
      upon drug treatment. Each drug is associated with unique selective advantage
      profiles that reflect its antiviral activity and mutant susceptibility. Five
      mutants (R155K/Q, A156T, and D168A/V) showed significant levels of selective
      advantage after treatment with >10 nM ( approximately 7 times the wild-type 50%
      effective concentration [EC50]) of BILN-2061. R155K displayed dominant levels of
      selective advantage over the other mutants upon treatment with ITMN-191 over a
      broad range of concentrations. Upon VX-950 treatment, various mutants (A156T,
      A156S, R155K, T54A, V170A, V36M/R155K, and R155Q) exhibited high levels of
      selective advantage in different drug concentration ranges, with A156T and A156S
      being the dominant mutants at >3 microM ( approximately 10 times the wild-type
      EC50) of VX-950. This method provides more accurate estimates of the behavior of
      various mutants under drug pressure than replication capacity analysis. We noted
      that the R155K mutant shows reduced susceptibility to all three PIs and
      significant selective advantage, raising concern over the potential emergence of
      R155K as a multidrug-resistant, highly fit mutant in HCV patients treated with
      PIs.

PMID- 18086852
TI  - AdeIJK, a resistance-nodulation-cell division pump effluxing multiple antibiotics
      in Acinetobacter baumannii.
AB  - We have identified a second resistance-nodulation-cell division (RND)-type efflux
      pump, AdeIJK, in clinical isolate Acinetobacter baumannii BM4454. The adeI, adeJ,
      and adeK genes encode, respectively, the membrane fusion, RND, and outer membrane
      components of the pump. AdeJ belongs to the AcrB protein family (57% identity
      with AcrB from Escherichia coli). mRNA analysis by Northern blotting and reverse
      transcription-PCR indicated that the genes were cotranscribed. Overexpression of
      the cloned adeIJK operon was toxic in both E. coli and Acinetobacter. The adeIJK
      genes were detected in all of the 60 strains of A. baumannii tested. The two
      latter observations suggest that the AdeIJK complex might contribute to intrinsic
      but not to acquired antibiotic resistance in Acinetobacter. To characterize the
      substrate specificity of the pump, we have constructed derivatives of BM4454 in
      which adeIJK (strain BM4579), adeABC (strain BM4561), or both groups of genes
      (strain BM4652) were inactivated by deletion-insertion. Determination of the
      antibiotic susceptibility of these strains and of BM4652 and BM4579, in which the
      adeIJK operon was provided in trans, indicated that the AdeIJK pump contributes
      to resistance to beta-lactams, chloramphenicol, tetracycline, erythromycin,
      lincosamides, fluoroquinolones, fusidic acid, novobiocin, rifampin, trimethoprim,
      acridine, safranin, pyronine, and sodium dodecyl sulfate. The chemical structure
      of these molecules suggests that amphiphilic compounds are the preferred
      substrates. The AdeABC and AdeIJK efflux systems contributed in a more than
      additive fashion to tigecycline resistance.

PMID- 18086853
TI  - In vitro capability of faropenem to select for resistant mutants of Streptococcus
      pneumoniae and Haemophilus influenzae.
AB  - When tested against nine strains of pneumococci and six of Haemophilus influenzae
      of various resistotypes, faropenem failed to select for resistant mutants after
      50 days of consecutive subculture in subinhibitory concentrations. Faropenem also
      yielded low rates of spontaneous mutations against all organisms of both species.
      By comparison, resistant clones were obtained with macrolides, ketolides, and
      quinolones.

PMID- 18086854
TI  - A sphingolipid inhibitor induces a cytokinesis arrest and blocks stage
      differentiation in Giardia lamblia.
AB  - Sphingolipid biosynthesis pathways have recently emerged as a promising target
      for therapeutic intervention against pathogens, including parasites. A key step
      in the synthesis of complex sphingolipids is the glucosylation of ceramide,
      mediated by glucosylceramide (GlcCer) synthase, whose activity can be inhibited
      by PPMP (1-phenyl-2-palmitoylamino-3-morpholino-1-propanol). In this study, we
      investigated whether PPMP inhibits the proliferation and differentiation of the
      pathogenic parasite Giardia lamblia, the major cause of parasite-induced diarrhea
      worldwide. PPMP was found to block in vitro parasite replication in a dose
      dependent manner, with a 50% inhibitory concentration of 3.5 muM. The inhibition
      of parasite replication was irreversible at 10 muM PPMP, a concentration that did
      not affect mammalian cell metabolism. Importantly, PPMP inhibited the completion
      of cell division at a specific stage in late cytokinesis. Microscopic analysis of
      cells incubated with PPMP revealed the aberrant accumulation of cellular
      membranes belonging to the endoplasmic reticulum network in the caudal area of
      the parasites. Finally, PPMP induced a 90% reduction in G. lamblia
      differentiation into cysts, the parasite stage responsible for the transmission
      of the disease. These results show that PPMP is a powerful inhibitor of G.
      lamblia in vitro and that as-yet-uncharacterized sphingolipid biosynthetic
      pathways are potential targets for the development of anti-G. lamblia agents.

PMID- 18086855
TI  - Systemic pharmacokinetics of rifaximin in volunteers with shigellosis.
AB  - Rifaximin is an oral antibiotic indicated for treatment of traveler's diarrhea.
      Rifaximin pharmacokinetics were evaluated in individuals challenged with Shigella
      flexneri. Peak plasma rifaximin concentrations were low after nine consecutive
      doses, and no accumulation was observed. Rifaximin serum levels were minimal and
      similar to those previously reported in studies of healthy volunteers.

PMID- 18086856
TI  - Induction of L1 and L2 beta-lactamases of Stenotrophomonas maltophilia.
AB  - Isogenic L1 and L2 gene knockout mutants of Stenotrophomonas maltophilia KJ
      (KJDeltaL1 and KJDeltaL2, respectively) were constructed by xylE gene
      replacement. Induction kinetics of the L1 and L2 genes were evaluated by testing
      catechol 2,3-dioxygenase activity in the mutants. The results suggested that the
      induction of the L1 and L2 genes was differentially regulated.

PMID- 18086857
TI  - Definition of global and transcript-specific mRNA export pathways in metazoans.
AB  - Eukaryotic gene expression requires export of messenger RNAs (mRNAs) from their
      site of transcription in the nucleus to the cytoplasm where they are translated.
      While mRNA export has been studied in yeast, the complexity of gene structure and
      cellular function in metazoan cells has likely led to increased diversification
      of these organisms' export pathways. Here we report the results of a genome-wide
      RNAi screen in which we identify 72 factors required for polyadenylated [poly
      (A(+))] mRNA export from the nucleus in Drosophila cells. Using structural and
      functional conservation analysis of yeast and Drosophila mRNA export factors, we
      expose the evolutionary divergence of eukaryotic mRNA export pathways.
      Additionally, we demonstrate the differential export requirements of two
      endogenous heat-inducible transcripts--intronless heat-shock protein 70 (HSP70)
      and intron-containing HSP83--and identify novel export factors that participate
      in HSP83 mRNA splicing. We characterize several novel factors and demonstrate
      their participation in interactions with known components of the Drosophila
      export machinery. One of these factors, Drosophila melanogaster PCI domain
      containing protein 2 (dmPCID2), associates with polysomes and may bridge the
      transition between exported messenger ribonucleoprotein particles (mRNPs) and
      polysomes. Our results define the global network of factors involved in
      Drosophila mRNA export, reveal specificity in the export requirements of
      different transcripts, and expose new avenues for future work in mRNA export.

PMID- 18086858
TI  - beta-Catenin is a Nek2 substrate involved in centrosome separation.
AB  - beta-Catenin plays important roles in cell adhesion and gene transcription, and
      has been shown recently to be essential for the establishment of a bipolar
      mitotic spindle. Here we show that beta-catenin is a component of interphase
      centrosomes and that stabilization of beta-catenin, mimicking mutations found in
      cancers, induces centrosome splitting. Centrosomes are held together by a dynamic
      linker regulated by Nek2 kinase and its substrates C-Nap1 (centrosomal Nek2
      associated protein 1) and Rootletin. We show that beta-catenin binds to and is
      phosphorylated by Nek2, and is in a complex with Rootletin. In interphase, beta
      catenin colocalizes with Rootletin between C-Nap1 puncta at the proximal end of
      centrioles, and this localization is dependent on C-Nap1 and Rootletin. In
      mitosis, when Nek2 activity increases, beta-catenin localizes to centrosomes at
      spindle poles independent of Rootletin. Increased Nek2 activity disrupts the
      interaction of Rootletin with centrosomes and results in binding of beta-catenin
      to Rootletin-independent sites on centrosomes, an event that is required for
      centrosome separation. These results identify beta-catenin as a component of the
      intercentrosomal linker and define a new function for beta-catenin as a key
      regulator of mitotic centrosome separation.

PMID- 18086859
TI  - IkappaB kinase beta-induced phosphorylation of CARMA1 contributes to CARMA1 Bcl10
      MALT1 complex formation in B cells.
AB  - Protein kinase C (PKC) beta has been reported (Shinohara, H., T. Yasuda, Y. Aiba,
      H. Sanjo, M. Hamadate, H. Watarai, H. Sakurai, and T. Kurosaki. 2005. J. Exp.
      Med. 202:1423-1431; Sommer, K., B. Guo, J.L. Pomerantz, A.D. Bandaranayake, M.E.
      Moreno-Garcia, Y.L. Ovechkina, and D.J. Rawlings. 2005. Immunity. 23:561-574) to
      play a crucial role in B cell receptor (BCR)-mediated IkappaB kinase (IKK)
      activation through phosphorylation of caspase recruitment domain 11, Bimp3
      (CARMA1). However, it remains unclear whether this PKCbeta-mediated
      phosphorylation accounts fully for the activation status of CARMA1, because
      involvement of other kinases, such as phosphoinositide 3-kinase-dependent kinase
      1, has also been suggested. We show that PKCbeta mediates phosphorylation of
      CARMA1 on Ser668, which in turn is essential for BCR-mediated CARMA1-Bcl10
      mucosal-associated lymphoid tissue 1 (MALT1) association and subsequent IKK
      activation. Our analyses also demonstrate that the downstream kinase IKKbeta
      contributes to facilitating formation of the complex CARMA1-Bcl10-MALT1 by
      mediating phosphorylation of CARMA1. Hence, our data suggest that PKCbeta is
      crucial for initial activation of IKK. The activated IKKbeta does not merely
      function as an effector enzyme but also modifies the upstream signaling complex
      through a feedback mechanism, thereby optimizing the strength and duration of the
      nuclear factor kappaB signal.

PMID- 18086860
TI  - Heavy chain-only antibodies are spontaneously produced in light chain-deficient
      mice.
AB  - In healthy mammals, maturation of B cells expressing heavy (H) chain
      immunoglobulin (Ig) without light (L) chain is prevented by chaperone association
      of the H chain in the endoplasmic reticulum. Camelids are an exception,
      expressing homodimeric IgGs, an antibody type that to date has not been found in
      mice or humans. In camelids, immunization with viral epitopes generates high
      affinity H chain-only antibodies, which, because of their smaller size, recognize
      clefts and protrusions not readily distinguished by typical antibodies.
      Developmental processes leading to H chain antibody expression are unknown. We
      show that L(-/-) (kappa(-/-)lambda(-/-)-deficient) mice, in which conventional B
      cell development is blocked at the immature B cell stage, produce diverse H chain
      only antibodies in serum. The generation of H chain-only IgG is caused by the
      loss of constant (C) gamma exon 1, which is accomplished by genomic alterations
      in C(H)1-circumventing chaperone association. These mutations can be attributed
      to errors in class switch recombination, which facilitate the generation of H
      chain-only Ig-secreting plasma cells. Surprisingly, transcripts with a similar
      deletion can be found in normal mice. Thus, naturally occurring H chain
      transcripts without C(H)1 (V(H)DJ(H)-hinge-C(H)2-C(H)3) are selected for and lead
      to the formation of fully functional and diverse H chain-only antibodies in L(-/
      ) animals.

PMID- 18086861
TI  - The dermis contains langerin+ dendritic cells that develop and function
      independently of epidermal Langerhans cells.
AB  - Langerhans cells (LCs) constitute a subset of dendritic cells (DCs) that express
      the lectin langerin and that reside in their immature state in epidermis.
      Paradoxically, in mice permitting diphtheria toxin (DT)-mediated ablation of LCs,
      epidermal LCs reappeared with kinetics that lagged behind that of their putative
      progeny found in lymph nodes (LNs). Using bone marrow (BM) chimeras, we showed
      that a major fraction of the langerin(+), skin-derived DCs found in LNs
      originates from a developmental pathway that is independent from that of
      epidermal LCs. This pathway, the existence of which was unexpected, originates in
      the dermis and gives rise to langerin(+) dermal DCs (DDCs) that should not be
      confused with epidermal LCs en route to LNs. It explains that after DT treatment,
      some langerin(+), skin-derived DCs reappear in LNs long before LC-derived DCs.
      Using CD45 expression and BrdU-labeling kinetics, both LCs and langerin(+) DDCs
      were found to coexist in wild-type mice. Moreover, DT-mediated ablation of
      epidermal LCs opened otherwise filled niches and permitted repopulation of adult
      noninflammatory epidermis with BM-derived LCs. Our results stress that the
      langerin(+) DC network is more complex than originally thought and have
      implications for the development of transcutaneous vaccines and the improvement
      of humanized mouse models.

PMID- 18086862
TI  - Blood-derived dermal langerin+ dendritic cells survey the skin in the steady
      state.
AB  - Langerin is a C-type lectin receptor that recognizes glycosylated patterns on
      pathogens. Langerin is used to identify human and mouse epidermal Langerhans
      cells (LCs), as well as migratory LCs in the dermis and the skin draining lymph
      nodes (DLNs). Using a mouse model that allows conditional ablation of langerin(+)
      cells in vivo, together with congenic bone marrow chimeras and parabiotic mice as
      tools to differentiate LC- and blood-derived dendritic cells (DCs), we have
      revisited the origin of langerin(+) DCs in the skin DLNs. Our results show that
      in contrast to the current view, langerin(+)CD8(-) DCs in the skin DLNs do not
      derive exclusively from migratory LCs, but also include blood-borne langerin(+)
      DCs that transit through the dermis before reaching the DLN. The recruitment of
      circulating langerin(+) DCs to the skin is dependent on endothelial selectins and
      CCR2, whereas their recruitment to the skin DLNs requires CCR7 and is independent
      of CD62L. We also show that circulating langerin(+) DCs patrol the dermis in the
      steady state and migrate to the skin DLNs charged with skin antigens. We propose
      that this is an important and previously unappreciated element of
      immunosurveillance that needs to be taken into account in the design of novel
      vaccine strategies.

PMID- 18086863
TI  - Talin is required for integrin-mediated platelet function in hemostasis and
      thrombosis.
AB  - Integrins are critical for hemostasis and thrombosis because they mediate both
      platelet adhesion and aggregation. Talin is an integrin-binding cytoplasmic
      adaptor that is a central organizer of focal adhesions, and loss of talin
      phenocopies integrin deletion in Drosophila. Here, we have examined the role of
      talin in mammalian integrin function in vivo by selectively disrupting the talin1
      gene in mouse platelet precursor megakaryocytes. Talin null megakaryocytes
      produced circulating platelets that exhibited normal morphology yet manifested
      profoundly impaired hemostatic function. Specifically, platelet-specific deletion
      of talin1 led to spontaneous hemorrhage and pathological bleeding. Ex vivo and in
      vitro studies revealed that loss of talin1 resulted in dramatically impaired
      integrin alphaIIbbeta3-mediated platelet aggregation and beta1 integrin-mediated
      platelet adhesion. Furthermore, loss of talin1 strongly inhibited the activation
      of platelet beta1 and beta3 integrins in response to platelet agonists. These
      data establish that platelet talin plays a crucial role in hemostasis and provide
      the first proof that talin is required for the activation and function of
      mammalian alpha2beta1 and alphaIIbbeta3 integrins in vivo.

PMID- 18086864
TI  - Loss of talin1 in platelets abrogates integrin activation, platelet aggregation,
      and thrombus formation in vitro and in vivo.
AB  - Platelet adhesion and aggregation at sites of vascular injury are essential for
      normal hemostasis but may also lead to pathological thrombus formation, causing
      diseases such as myocardial infarction or stroke. Heterodimeric receptors of the
      integrin family play a central role in the adhesion and aggregation of platelets.
      In resting platelets, integrins exhibit a low affinity state for their ligands,
      and they shift to a high affinity state at sites of vascular injury. It has been
      proposed that direct binding of the cytoskeletal protein talin1 to the
      cytoplasmic domain of the integrin beta subunits is necessary and sufficient to
      trigger the activation of integrins to this high affinity state, but direct in
      vivo evidence in support of this hypothesis is still lacking. Here, we show that
      platelets from mice lacking talin1 are unable to activate integrins in response
      to all known major platelet agonists while other cellular functions are still
      preserved. As a consequence, mice with talin-deficient platelets display a severe
      hemostatic defect and are completely resistant to arterial thrombosis.
      Collectively, these experiments demonstrate that talin is required for inside-out
      activation of platelet integrins in hemostasis and thrombosis.

PMID- 18086865
TI  - Identification of a novel population of Langerin+ dendritic cells.
AB  - Langerhans cells (LCs) are antigen-presenting cells that reside in the epidermis
      of the skin and traffic to lymph nodes (LNs). The general role of these cells in
      skin immune responses is not clear because distinct models of LC depletion
      resulted in opposite conclusions about their role in contact hypersensitivity
      (CHS) responses. While comparing these models, we discovered a novel population
      of LCs that resides in the dermis and does not represent migrating epidermal LCs,
      as previously thought. Unlike epidermal LCs, dermal Langerin(+) dendritic cells
      (DCs) were radiosensitive and displayed a distinct cell surface phenotype. Dermal
      Langerin(+) DCs migrate from the skin to the LNs after inflammation and in the
      steady state, and represent the majority of Langerin(+) DCs in skin draining LNs.
      Both epidermal and dermal Langerin(+) DCs were depleted by treatment with
      diphtheria toxin in Lang-DTREGFP knock-in mice. In contrast, transgenic hLang-DTA
      mice lack epidermal LCs, but have normal numbers of dermal Langerin(+) DCs. CHS
      responses were abrogated upon depletion of both epidermal and dermal LCs, but
      were unaffected in the absence of only epidermal LCs. This suggests that dermal
      LCs can mediate CHS and provides an explanation for previous differences observed
      in the two-model systems.

PMID- 18086866
TI  - Show me the data.

PMID- 18086868
TI  - Synergistic effects of betaine and conjugated linoleic acid on the growth and
      carcass composition of growing Iberian pigs.
AB  - An experiment was conducted to determine the efficacy of dietary betaine, CLA, or
      both as growth promotants and carcass modifiers in growing Iberian pigs. Twenty
      gilts (20 kg of BW) were individually penned and fed barley- and soybean meal
      based diets (12% CP, 0.81% Lys, and 14.8 MJ of ME/kg of DM) containing either no
      added betaine or CLA (control), 0.5% betaine, 1% CLA, or 0.5% betaine + 1% CLA,
      at 95% of ad libitum energy intake. An additional group of 5 pigs was slaughtered
      at the beginning of the experiment to obtain the initial body composition. At 30
      kg of BW, a balance experiment was conducted. At 50 kg of BW, pigs were
      slaughtered and viscera was removed and weighed. Betaine or CLA alone did not
      affect growth performance. However, betaine + CLA increased ADG (601 vs. 558 g, P
      = 0.03) and gain relative to ME intake (25.4 vs. 22.2 g/MJ, P = 0.03) compared
      with control pigs. Digestibility of nutrients and metabolizability of energy did
      not differ among diets (P = 0.46 to 0.75). Carcass protein, water, and lean
      deposition (g/d) increased (19.8, 24.2, and 23.4%, respectively, P < 0.01) in
      pigs fed betaine + CLA compared with control pigs. Similarly, protein deposition
      relative to ME intake increased by 28% in betaine + CLA-supplemented pigs (P <
      0.05). Fat and mineral deposition did not differ among treatments. Carcass
      protein, water, and lean content (g/kg of carcass) of pigs fed betaine + CLA
      supplemented diets tended to increase (P = 0.07 to 0.09) and carcass fat content
      tended to decrease (P = 0.09). Similarly, estimated composition of carcass gain
      was affected, such that water and lean content tended to increase (P = 0.06 to
      0.08), whereas fat tended to decrease (P = 0.08) in pigs fed betaine + CLA
      supplemented diets. Longissimus muscle area was not altered by treatments (P =
      0.49). The liver of pigs fed betaine + CLA diets had increased weight (19%, P <
      0.05) compared with control pigs. Overall, dietary supplementation of betaine +
      CLA increased ADG, protein, water, and lean deposition in growing Iberian gilts.
      There appears to be a synergistic action when betaine and CLA are used together.

PMID- 18086869
TI  - Evaluation of secondary protein nutrients as a substitute for soybean meal in
      diets for beef steers and meat goats.
AB  - Finding appropriate disposal techniques for waste products is one of many
      challenges facing the poultry-processing industry. One waste generated in
      significant quantities is dissolved air floatation sludge, a product of
      wastewater treatment. Converting dissolved air floatation sludge into a dry feed
      product (meal) for incorporation into livestock feed appears to be a viable
      solution. This meal, called secondary protein nutrients (SPN), is high in protein
      (45% CP), fat (28% crude fat), and minerals. The protein consists of 85% B(2) and
      B(3) fractions, which are moderately to slowly degradable in the rumen, and
      therefore may potentially escape ruminal degradation and be available for
      digestion in the lower gastrointestinal tract. The goal of this research was to
      evaluate SPN as an alternative to traditional protein sources for ruminants by
      substituting it on an equivalent N basis for soybean meal in cattle and meat goat
      diets (0, 25, 50, 75, and 100% for cattle; 0, 20, and 40% for goats). When
      included in corn silage-based steer diets, increasing SPN resulted in linear and
      quadratic declines in both DMI and ADG (P < 0.001). Dry matter intake diminished
      with inclusion rates above 50%, and ADG were reduced after inclusion of SPN
      reached 25% of added N. Feed efficiency (the reciprocal of the efficiency of
      gain, which is represented by G:F) declined linearly (P < 0.001) with each
      incremental increase in SPN. Addition of up to 40% added N as SPN in goat diets
      caused no change in DMI, digestibility of DM or fiber, or N retention. Ruminal
      VFA concentrations showed little variation in either species. Increasing the
      proportion of SPN in the feed caused linear declines in ruminal NH(3) in steers
      (P < 0.001). Increasing SPN in goat diets, however, resulted in only a trend
      toward reductions of this parameter (P = 0.14). The decreases observed may have
      resulted from decreasing ruminal protein degradability or increasing fat caused
      by increasing the proportion of SPN in the feed. Urinary urea N as a percentage
      of urinary N showed significant declines in cattle, but not in goats, over the
      ranges of SPN offered. These results indicate that SPN can be included in diets
      for ruminants to supply up to 40% of supplemental N with little negative impact
      on animal performance.

PMID- 18086871
TI  - Specific plasma membrane protein phenotype of culture-amplified and native human
      bone marrow mesenchymal stem cells.
AB  - We have studied the plasma membrane protein phenotype of human culture-amplified
      and native bone marrow mesenchymal stem cells (BM MSCs). We have found, using
      microarrays and flow cytometry, that cultured cells express specifically 113
      transcripts and 17 proteins that were not detected in hematopoietic cells. These
      antigens define a lineage-homogenous cell population of mesenchymal cells,
      clearly distinct from the hematopoietic lineages, and distinguishable from other
      cultured skeletal mesenchymal cells (periosteal cells and synovial fibroblasts).
      Among the specific membrane proteins present on cultured MSCs, 9 allowed the
      isolation from BM mononuclear cells of a minute population of native MSCs. The
      enrichment in colony-forming units-fibroblasts was low for CD49b, CD90, and
      CD105, but high for CD73, CD130, CD146, CD200, and integrin alphaV/beta5. In
      addition, the expression of CD73, CD146, and CD200 was down-regulated in
      differentiated cells. The new marker CD200, because of its specificity and
      immunomodulatory properties, deserves further in-depth studies.

PMID- 18086870
TI  - TLR9 engagement on CD4 T lymphocytes represses gamma-radiation-induced apoptosis
      through activation of checkpoint kinase response elements.
AB  - T cell-based therapies have much promise in cancer treatment. This approach may
      be enhanced if used in combination with radiotherapy provided that tumor-specific
      T cells can be protected against the effects of radiotherapy. Previously, we
      demonstrated that administration of TLR9 ligand into mice decreased activation-
      and serum deprivation-induced cell death in T cells. We hypothesized that TLR9
      engagement on T lymphocytes decreased apoptosis after cellular stress. We show
      that TLR9 engagement on murine CD4 T cells reduces gamma-radiation-induced
      apoptosis as judged by decreased annexin-V/PI staining, caspase-3 activation, and
      PARP cleavage. TLR9-stimulated cells show heightened accumulation at the G2 cell
      cycle phase and increased DNA repair rates. Irradiated, TLR9-engaged cells showed
      higher levels of phosphorylated Chk1 and Chk2. While the levels of activated ATM
      in response to IR did not differ between TLR9-stimulated and unstimulated cells,
      inhibition of ATM/ATR and Chk1/Chk2 kinases abolished the radioprotective effects
      in TLR9-stimulated cells. In vivo, TLR9-stimulated cells displayed higher radio
      resistance than TLR9-stimulated MyD88(-/-) T cells and responded to antigenic
      stimulation after total body irradiation. These findings show, for the first
      time, that TLR9 engagement on CD4 T cells reduces IR-induced apoptosis by
      influencing cell-cycle checkpoint activity, potentially allowing for
      combinatorial immunotherapy and radiotherapy.

PMID- 18086872
TI  - Extracting global system dynamics of corticosteroid genomic effects in rat liver.
AB  - One of the challenges in constructing biological models involves resolving
      meaningful data patterns from which the mathematical models will be generated.
      For models that describe the change of mRNA in response to drug administration,
      questions exist whether the correct genes have been selected given the myriad
      transcriptional effects that may occur. Oftentimes, different algorithms will
      select or cluster different groups of genes from the same data set. A new
      approach was developed that focuses on identifying the underlying global dynamics
      of the system instead of selecting individual genes. The procedure was applied to
      microarray genomic data obtained from rat liver after a large single dose of
      methylprednisolone in 52 adrenalectomized rats. Twelve clusters of at least 30
      genes each were selected, reflecting the major changes over time. This method
      along with isolating the underlying dynamics of the system also extracts and
      clusters the genes that make up this global dynamic for further analysis as to
      the contributions of specific mechanisms affected by the drug.

PMID- 18086873
TI  - Prediction of mortality using measures of cardiac autonomic dysfunction in the
      diabetic and nondiabetic population: the MONICA/KORA Augsburg Cohort Study.
AB  - OBJECTIVES: To evaluate whether reduced heart rate variability (HRV), prolonged
      corrected QT (QTc) interval, or increased QT dispersion (QTD) are predictors of
      mortality in the general diabetic and nondiabetic population. RESEARCH DESIGN AND
      METHODS: Nondiabetic (n = 1,560) and diabetic (n = 160) subjects aged 55-74 years
      were assessed to determine whether reduced HRV, prolonged QTc interval, and
      increased QTD may predict all-cause mortality. Lowest quartiles for the maximum
      minimum R-R interval difference (max-min, as measured at baseline from a 20-s
      standard 12-lead resting electrocardiogram without controlling for depth and rate
      of respiration), QTc >440 ms and QTD >60 ms, were used as cutpoints. RESULTS:
      During a 9-year follow-up, 10.5% of the nondiabetic and 30.6% of the diabetic
      population deceased. In the nondiabetic individuals, multivariate Cox
      proportional hazard models adjusted for cardiovascular risk factors and
      demographic variables showed that prolonged QTc interval (hazard ratio 2.02 [95%
      CI 1.29-3.17]; P = 0.002) but not low max-min (0.93 [0.65-1.34]; P = 0.700), and
      increased QTD (0.98 [0.60-1.60]; P = 0.939) were associated with increased
      mortality. In the diabetic subjects, prolonged QTc was also a predictor of
      mortality (3.00 [1.34-6.71]; P = 0.007), while a trend for an increased risk was
      noted in those with low max-min (1.74 [0.95-3.18]; P = 0.075), whereas increased
      QTD did not predict mortality (0.42 [0.06-3.16]; P = 0.402). CONCLUSIONS:
      Prolonged QTc interval, but not increased QTD, is an independent predictor of a
      twofold and threefold increased risk of mortality in the nondiabetic and diabetic
      elderly general population, respectively. Low HRV during spontaneous breathing
      tends to be associated with excess mortality in the diabetic but not nondiabetic
      population.

PMID- 18086874
TI  - Is a failure to recognize an increase in food intake a key to understanding
      insulin-induced weight gain?
AB  - The present study aimed to assess the contribution of energy intake to positive
      energy balance and weight gain with insulin therapy. Changes in energy intake
      (self-report and weighed food intake), dietary behavior (auto-questionnaires),
      resting energy expenditure (REE) (indirect calorimetry), physical activity
      (accelerometry), and glucosuria were monitored over the first 6 months of insulin
      therapy in 46 diabetic adults. No change in REE, activity, or glucosuria could
      explain weight gain in the type 1 (4.1 +/- 0.6 kg, P < 0.0001) or type 2 (1.8 +/-
      0.8 kg, P = 0.02) diabetic groups. An increase in energy intake provides the most
      likely explanation for weight gain with insulin. However, it is not being
      recognized because of significant underestimation of self-reported food intake,
      which appears to be associated with increased dietary restraint.

PMID- 18086875
TI  - The atypical Rho GTPase Wrch1 collaborates with the nonreceptor tyrosine kinases
      Pyk2 and Src in regulating cytoskeletal dynamics.
AB  - The Cdc42-like GTPase Wnt responsive Cdc42 homolog 1 (Wrch1) has several atypical
      features; it has an N-terminal proline-rich extension that confers binding to SH3
      domains, and it harbors an extremely high intrinsic nucleotide exchange activity,
      which overrides the normal GTPase activity. As a result, Wrch1 resides mainly in
      the active, GTP-loaded conformation under normal cellular conditions. We have
      previously shown that ectopic expression of Wrch1 in fibroblasts resulted in an
      altered cell morphology visible as a formation of filopodia, a loss of stress
      fibers, and a reduction in focal adhesions. Here, we show that Wrch1 binds to the
      nonreceptor tyrosine kinase Pyk2. The interaction required Wrch1 to be in a GTP
      conformation and also required an intact N-terminal proline-rich extension as
      well as an intact effector loop. Wrch1 requires Pyk2 in imposing the cytoskeletal
      effects, seen as the formation of filopodia, since treatment of cells with a Pyk2
      specific small interfering RNA abrogated this response. Interestingly, we found
      that the presence and activity of Src were needed for the formation of a Wrch1
      Pyk2 complex as well as for the Wrch1-induced formation of filopodia. We propose
      a model in which Pyk2 and Src function to coordinate the Wrch1-dependent effects
      on cytoskeletal dynamics.

PMID- 18086876
TI  - Glucose-dependent insulinotropic polypeptide-mediated up-regulation of beta-cell
      antiapoptotic Bcl-2 gene expression is coordinated by cyclic AMP (cAMP) response
      element binding protein (CREB) and cAMP-responsive CREB coactivator 2.
AB  - The cyclic AMP (cAMP)/protein kinase A (PKA) cascade plays a central role in beta
      cell proliferation and apoptosis. Here, we show that the incretin hormone glucose
      dependent insulinotropic polypeptide (GIP) stimulates expression of the
      antiapoptotic Bcl-2 gene in pancreatic beta cells through a pathway involving AMP
      activated protein kinase (AMPK), cAMP-responsive CREB coactivator 2 (TORC2), and
      cAMP response element binding protein (CREB). Stimulation of beta-INS-1 (clone
      832/13) cells with GIP resulted in increased Bcl-2 promoter activity. Analysis of
      the rat Bcl-2 promoter revealed two potential cAMP response elements, one of
      which (CRE-I [GTGACGTAC]) was shown, using mutagenesis and deletion analysis, to
      be functional. Subsequent studies established that GIP increased the nuclear
      localization of TORC2 and phosphorylation of CREB serine 133 through a pathway
      involving PKA activation and reduced AMPK phosphorylation. At the nuclear level,
      phospho-CREB and TORC2 were demonstrated to bind to CRE-I of the Bcl-2 promoter,
      and GIP treatment resulted in increases in their interaction. Furthermore, GIP
      mediated cytoprotection was partially reversed by small interfering RNA-mediated
      reduction in BCL-2 or TORC2/CREB or by pharmacological activation of AMPK. The
      antiapoptotic effect of GIP in beta cells is therefore partially mediated through
      a novel mode of transcriptional regulation of Bcl-2 involving cAMP/PKA/AMPK
      dependent regulation of CREB/TORC2 activity.

PMID- 18086877
TI  - Role of hPHF1 in H3K27 methylation and Hox gene silencing.
AB  - Polycomb group (PcG) proteins are required for maintaining the silent state of
      the homeotic genes and other important developmental regulators. The silencing
      function of the PcG proteins has been linked to their intrinsic histone modifying
      enzymatic activities. The EED-EZH2 complex, containing the core subunits EZH2,
      EED, SUZ12, and RbAp48, functions as a histone H3K27-specific methyltransferase.
      Here we describe the identification and characterization of a related EED-EZH2
      protein complex which is distinguished from the previous complex by the presence
      of another PcG protein, hPHF1. Consistent with the ability of hPHF1 to stimulate
      the enzymatic activity of the core EED-EZH2 complex in vitro, manipulation of
      mPcl1, the mouse counterpart of hPHF1, in NIH 3T3 cells and cells of the mouse
      male germ cell line GC1spg results in global alteration of H3K27me2 and H3K27me3
      levels and Hox gene expression. Small interfering RNA-mediated knockdown of mPcl1
      affects association of the Eed-Ezh2 complex with certain Hox genes, such as
      HoxA10, as well as Hox gene expression concomitant with an alteration on the
      H3K27me2 levels of the corresponding promoters. Therefore, our results reveal
      hPHF1 as a component of a novel EED-EZH2 complex and demonstrate its important
      role in H3K27 methylation and Hox gene silencing.

PMID- 18086878
TI  - Two RNA polymerase I subunits control the binding and release of Rrn3 during
      transcription.
AB  - Rpa34 and Rpa49 are nonessential subunits of RNA polymerase I, conserved in
      species from Saccharomyces cerevisiae and Schizosaccharomyces pombe to humans.
      Rpa34 bound an N-terminal region of Rpa49 in a two-hybrid assay and was lost from
      RNA polymerase in an rpa49 mutant lacking this Rpa34-binding domain, whereas
      rpa34Delta weakened the binding of Rpa49 to RNA polymerase. rpa34Delta mutants
      were caffeine sensitive, and the rpa34Delta mutation was lethal in a top1Delta
      mutant and in rpa14Delta, rpa135(L656P), and rpa135(D395N) RNA polymerase
      mutants. These defects were shared by rpa49Delta mutants, were suppressed by the
      overexpression of Rpa49, and thus, were presumably mediated by Rpa49 itself.
      rpa49 mutants lacking the Rpa34-binding domain behaved essentially like
      rpa34Delta mutants, but strains carrying rpa49Delta and rpa49-338::HIS3 (encoding
      a form of Rpa49 lacking the conserved C terminus) had reduced polymerase
      occupancy at 30 degrees C, failed to grow at 25 degrees C, and were sensitive to
      6-azauracil and mycophenolate. Mycophenolate almost fully dissociated the mutant
      polymerase from its ribosomal DNA (rDNA) template. The rpa49Delta and rpa49
      338::HIS3 mutations had a dual effect on the transcription initiation factor Rrn3
      (TIF-IA). They partially impaired its recruitment to the rDNA promoter, an effect
      that was bypassed by an N-terminal deletion of the Rpa43 subunit encoded by rpa43
      35,326, and they strongly reduced the release of the Rrn3 initiation factor
      during elongation. These data suggest a dual role of the Rpa49-Rpa34 dimer during
      the recruitment of Rrn3 and its subsequent dissociation from the elongating
      polymerase.

PMID- 18086879
TI  - Slx5 promotes transcriptional silencing and is required for robust growth in the
      absence of Sir2.
AB  - The broadly conserved Sir2 NAD(+)-dependent deacetylase is required for chromatin
      silencing. Here we report the discovery of physical and functional links between
      Sir2 and Slx5 (Hex3), a RING domain protein and subunit of the Slx5/8 complex,
      [corrected] which is a ubiquitin E3 ligase that targets sumoylated proteins. Slx5
      interacted with Sir2 by two-hybrid and glutathione S-transferase-binding assays
      and was found to promote silencing of genes at telomeric or ribosomal DNA (rDNA)
      loci. However, deletion of SLX5 had no detectable effect on the distribution of
      silent chromatin components and only slightly altered the deacetylation of
      histone H4 lysine 16 at the telomere. In vivo assays indicated that Sir2
      dependent silencing was functionally intact in the absence of Slx5. Although no
      previous reports suggest that Sir2 contributes to the fitness of yeast
      populations, we found that Sir2 was required for maximal growth in slx5Delta
      mutant cells. A similar requirement was observed for mutants of the SUMO
      isopeptidase Ulp2/Smt4. The contribution of Sir2 to optimal growth was not due to
      known Sir2 roles in mating-type determination or rDNA maintenance but was
      connected to a role of sumoylation in transcriptional silencing. These results
      indicate that Sir2 and Slx5 jointly contribute to transcriptional silencing and
      robust cellular growth.

PMID- 18086880
TI  - ARS2 is a conserved eukaryotic gene essential for early mammalian development.
AB  - Determining the functions of novel genes implicated in cell survival is directly
      relevant to our understanding of mammalian development and carcinogenesis. ARS2
      is an evolutionarily conserved gene that confers arsenite resistance on arsenite
      sensitive Chinese hamster ovary cells. Little is known regarding the function of
      ARS2 in mammals. We report that ARS2 is transcribed throughout embryonic
      development and is expressed ubiquitously in mouse and human tissues. The mouse
      ARS2 protein is predominantly localized to the nucleus, and this nuclear
      localization is ablated in ARS2-null embryos, which in turn die around the time
      of implantation. After 24 h of culture, ARS2-null blastocysts contained a
      significantly greater number of apoptotic cells than wild-type or heterozygous
      blastocysts. By 48 h of in vitro culture, null blastocysts invariably collapsed
      and failed to proliferate. These data indicate ARS2 is essential for early
      mammalian development and is likely involved in an essential cellular process.
      The analysis of data from several independent protein-protein interaction studies
      in mammals, combined with functional studies of its Arabidopsis ortholog,
      SERRATE, suggests that this essential process is related to RNA metabolism.

PMID- 18086881
TI  - Incorporation of the noncoding roX RNAs alters the chromatin-binding specificity
      of the Drosophila MSL1/MSL2 complex.
AB  - The male-specific lethal (MSL) protein-RNA complex is required for X chromosome
      dosage compensation in Drosophila melanogaster. The MSL2 and MSL1 proteins form a
      complex and are essential for X chromosome binding. In addition, the MSL complex
      must integrate at least one of the noncoding roX RNAs for normal X chromosome
      binding. Here we find the amino-terminal RING finger domain of MSL2 binds as a
      complex with MSL1 to the heterochromatic chromocenter and a few sites on the
      chromosome arms. This binding required the same amino-terminal basic motif of
      MSL1 previously shown to be essential for binding to high-affinity sites on the X
      chromosome. While the RING finger domain of MSL2 is sufficient to increase the
      expression of roX1 in females, activation of roX2 requires motifs in the carboxyl
      terminal domain. Binding to hundreds of sites on the X chromosome and efficient
      incorporation of the roX RNAs into the MSL complex require proline-rich and basic
      motifs in the carboxyl-terminal domain of MSL2. We suggest that incorporation of
      the roX RNAs into the MSL complex alters the binding specificity of the chromatin
      binding module formed by the amino-terminal domains of MSL1 and MSL2.

PMID- 18086882
TI  - DNA polymerase delta is preferentially recruited during homologous recombination
      to promote heteroduplex DNA extension.
AB  - DNA polymerases play a central role during homologous recombination (HR), but the
      identity of the enzyme(s) implicated remains elusive. The pol3-ct allele of the
      gene encoding the catalytic subunit of DNA polymerase delta (Poldelta) has
      highlighted a role for this polymerase in meiotic HR. We now address the
      ubiquitous role of Poldelta during HR in somatic cells. We find that pol3-ct
      affects gene conversion tract length during mitotic recombination whether the
      event is initiated by single-strand gaps following UV irradiation or by site
      specific double-strand breaks. We show that the pol3-ct effects on gene
      conversion are completely independent of mismatch repair, indicating that shorter
      gene conversion tracts in pol3-ct correspond to shorter extensions of primed DNA
      synthesis. Interestingly, we find that shorter repair tracts do not favor
      synthesis-dependent strand annealing at the expense of double-strand-break
      repair. Finally, we show that the DNA polymerases that have been previously
      suspected to mediate HR repair synthesis (Polepsilon and Poleta) do not affect
      gene conversion during induced HR, including in the pol3-ct background. Our
      results argue strongly for the preferential recruitment of Poldelta during HR.

PMID- 18086883
TI  - Phosphorylation by casein kinase 2 regulates Nap1 localization and function.
AB  - In Saccharomyces cerevisiae, the evolutionarily conserved nucleocytoplasmic
      shuttling protein Nap1 is a cofactor for the import of histones H2A and H2B, a
      chromatin assembly factor and a mitotic factor involved in regulation of bud
      formation. To understand the mechanism by which Nap1 function is regulated, Nap1
      interacting factors were isolated and identified by mass spectrometry. We
      identified several kinases among these proteins, including casein kinase 2 (CK2),
      and a new bud neck-associated protein, Nba1. Consistent with our identification
      of the Nap1-interacting kinases, we showed that Nap1 is phosphorylated in vivo at
      11 sites and that Nap1 is phosphorylated by CK2 at three substrate serines.
      Phosphorylation of these serines was not necessary for normal bud formation, but
      mutation of these serines to either alanine or aspartic acid resulted in cell
      cycle changes, including a prolonged S phase, suggesting that reversible
      phosphorylation by CK2 is important for cell cycle regulation. Nap1 can shuttle
      between the nucleus and cytoplasm, and we also showed that CK2 phosphorylation
      promotes the import of Nap1 into the nucleus. In conclusion, our data show that
      Nap1 phosphorylation by CK2 appears to regulate Nap1 localization and is required
      for normal progression through S phase.

PMID- 18086884
TI  - Localization to the cortical cytoskeleton is necessary for Nf2/merlin-dependent
      epidermal growth factor receptor silencing.
AB  - Merlin, the product of the NF2 tumor suppressor gene, is closely related to the
      ERM (ezrin, radixin, moesin) proteins, which provide anchorage between membrane
      proteins and the underlying cortical cytoskeleton; all four proteins are members
      of the band 4.1 superfamily. Despite their similarity, the subcellular
      distributions and functional properties of merlin and the ERM proteins are
      largely distinct. Upon cell-cell contact merlin prevents internalization of and
      signaling from the epidermal growth factor receptor (EGFR) by sequestering it
      into an insoluble membrane compartment. Here we show that the extreme amino (N)
      terminus directs merlin biochemically to an insoluble membrane compartment and
      physically to the cortical actin network, with a marked concentration along cell
      cell boundaries. This insoluble-membrane distribution is required for the growth
      suppressing function of merlin and for the functional association of merlin with
      EGFR and other membrane receptors. Our data support a model whereby locally
      activated merlin sequesters membrane receptors such as EGFR at the cortical
      network, contributing to the long-held observation that the cortical actin
      cytoskeleton can control the lateral mobility of and signaling from certain
      membrane receptors.

PMID- 18086885
TI  - Pat1 contains distinct functional domains that promote P-body assembly and
      activation of decapping.
AB  - The control of mRNA degradation and translation are important aspects of gene
      regulation. Recent results suggest that translation repression and mRNA decapping
      can be intertwined and involve the formation of a quiescent mRNP, which can
      accumulate in cytoplasmic foci referred to as P bodies. The Pat1 protein is a key
      component of this complex and an important activator of decapping, yet little is
      known about its function. In this work, we analyze Pat1 in Saccharomyces
      cerevisiae function by deletion and functional analyses. Our results identify two
      primary functional domains in Pat1: one promoting translation repression and P
      body assembly and a second domain promoting mRNA decapping after assembly of the
      mRNA into a P-body mRNP. In addition, we provide evidence that Pat1 binds RNA and
      has numerous domain-specific interactions with mRNA decapping factors. These
      results indicate that Pat1 is an RNA binding protein and a multidomain protein
      that functions at multiple stages in the process of translation repression and
      mRNA decapping.

PMID- 18086886
TI  - Galpha12/Galpha13 deficiency causes localized overmigration of neurons in the
      developing cerebral and cerebellar cortices.
AB  - The heterotrimeric G proteins G(12) and G(13) link G-protein-coupled receptors to
      the regulation of the actin cytoskeleton and the induction of actomyosin-based
      cellular contractility. Here we show that conditional ablation of the genes
      encoding the alpha-subunits of G(12) and G(13) in the nervous system results in
      neuronal ectopia of the cerebral and cerebellar cortices due to overmigration of
      cortical plate neurons and cerebellar Purkinje cells, respectively. The
      organization of the radial glia and the basal lamina was not disturbed, and the
      Cajal-Retzius cell layer had formed normally in mutant mice. Embryonic cortical
      neurons lacking G(12)/G(13) were unable to retract their neurites in response to
      lysophosphatidic acid and sphingosine-1-phosphate, indicating that they had lost
      the ability to respond to repulsive mediators acting via G-protein-coupled
      receptors. Our data indicate that G(12)/G(13)-coupled receptors mediate stop
      signals and are required for the proper positioning of migrating cortical plate
      neurons and Purkinje cells during development.

PMID- 18086887
TI  - MDMX promotes proteasomal turnover of p21 at G1 and early S phases independently
      of, but in cooperation with, MDM2.
AB  - We have shown previously that MDM2 promotes the degradation of the cyclin
      dependent kinase inhibitor p21 through a ubiquitin-independent proteolytic
      pathway. Here we report that the MDM2 analog, MDMX, also displays a similar
      activity. MDMX directly bound to p21 and mediated its proteasomal degradation.
      Although the MDMX effect was independent of MDM2, they synergistically promoted
      p21 degradation when coexpressed in cells. This degradation appears to be
      mediated by the 26S proteasome, as MDMX and p21 bound to S2, one of the subunits
      of the 19S component of the 26S proteasome, in vivo. Conversely, knockdown of
      MDMX induced the level of endogenous p21 proteins that no longer cofractionated
      with 26S proteasome, resulting in G(1) arrest. The level of p21 was low at early
      S phase but markedly induced by knocking down either MDMX or MDM2 in human cells.
      Ablation of p21 rescued the G(1) arrest caused by double depletion of MDM2 and
      MDMX in p53-null cells. These results demonstrate that MDMX and MDM2
      independently and cooperatively regulate the proteasome-mediated degradation of
      p21 at the G(1) and early S phases.

PMID- 18086888
TI  - Identification of the proteins, including MAGEG1, that make up the human SMC5-6
      protein complex.
AB  - The SMC protein complexes play important roles in chromosome dynamics. The
      function of the SMC5-6 complex remains unclear, though it is involved in
      resolution of different DNA structures by recombination. We have now identified
      and characterized the four non-SMC components of the human complex and in
      particular demonstrated that the MAGEG1 protein is part of this complex. MAGE
      proteins play important but as yet undefined roles in carcinogenesis, apoptosis,
      and brain development. We show that, with the exception of the SUMO ligase
      hMMS21/hNSE2, depletion of any of the components results in degradation of all
      the other components. Depletion also confers sensitivity to methyl
      methanesulfonate. Several of the components are modified by sumoylation and
      ubiquitination.

PMID- 18086889
TI  - The HSA domain of BRG1 mediates critical interactions required for glucocorticoid
      receptor-dependent transcriptional activation in vivo.
AB  - The packaging of eukaryotic DNA into chromatin can create an impediment to
      transcription by hindering binding of essential factors required for
      transcription. The mammalian SWI/SNF remodeling complex has been shown to alter
      local chromatin structure and facilitate recruitment of transcription factors.
      BRG1 (or hBrm), the central ATPase of the human SWI/SNF complex, is a critical
      factor for the functional activity of nuclear receptor complexes. Analysis using
      BRG1/SNF2h chimeras suggests BRG1 may contain previously uncharacterized
      functional motifs important for SWI/SNF. To identify these regions, BRG1
      truncation and deletion mutants were designed, characterized, and utilized in a
      series of assays to evaluate transcriptional activation and chromatin remodeling
      by the glucocorticoid receptor. We identified a domain within the N terminus of
      BRG1 that mediates critical protein interactions within SWI/SNF. We find the HSA
      domain of BRG1 is required to mediate the interaction with BAF250a/ARID1A and
      show this association is necessary for transcriptional activation from chromatin
      mouse mammary tumor virus or endogenous promoters in vivo. These studies suggest
      BAF250a is a necessary facilitator of BRG1-mediated chromatin remodeling required
      for SWI/SNF-dependent transcriptional activation.

PMID- 18086890
TI  - Regulation of MyD88-dependent signaling events by S nitrosylation retards toll
      like receptor signal transduction and initiation of acute-phase immune responses.
AB  - Nitric oxide (NO) has been thought to regulate the immune system through S
      nitrosylation of the transcriptional factor NF-kappaB. However, regulatory
      effects of NO on innate immune responses are unclear. Here, we report that NO has
      a capability to control Toll-like receptor-mediated signaling through S
      nitrosylation. We found that the adaptor protein MyD88 was primarily S
      nitrosylated, depending on the presence of endothelial NO synthase (eNOS). S
      nitrosylation at a particular cysteine residue within the TIR domain of MyD88
      resulted in slight reduction of the NF-kappaB-activating property. This
      modification could be restored by the antioxidant glutathione. Through S
      nitrosylation, NO could negatively regulate the multiple steps of MyD88
      functioning, including translocation to the cell membrane after LPS stimulation,
      interaction with TIRAP, binding to TRAF6, and induction of IkappaBalpha
      phosphorylation. Interestingly, glutathione could reversely neutralize such NO
      derived effects. We also found that an acute febrile response to LPS was
      precipitated in eNOS-deficient mice, indicating that eNOS-derived NO exerts an
      initial suppressive effect on inflammatory processes. Thus, NO has a potential to
      retard induction of MyD88-dependent signaling events through the reversible and
      oxidative modification by NO, by which precipitous signaling reactions are
      relieved. Such an effect may reflect appropriate regulation of the acute-phase
      inflammatory responses in living organisms.

PMID- 18086891
TI  - Retrotransposon target site selection by imitation of a cellular protein.
AB  - Mobile elements rely on cellular processes to replicate, and therefore, mobile
      element proteins frequently interact with a variety of cellular factors. The
      integrase (IN) encoded by the retrotransposon Ty5 interacts with the
      heterochromatin protein Sir4, and this interaction determines Ty5's preference to
      integrate into heterochromatin. We explored the hypothesis that Ty5's targeting
      mechanism arose by mimicking an interaction between Sir4 and another cellular
      protein(s). Mutational analyses defined the requirements for the IN-Sir4
      interaction, providing criteria to screen for cellular analogues. Esc1, a protein
      associated with the inner nuclear membrane, interacted with the same domain of
      Sir4 as IN, and 75% of mutations that disrupted IN-Sir4 interactions also
      abrogated Esc1-Sir4 interactions. A small motif critical for recognizing Sir4 was
      identified in Esc1. The functional equivalency of this motif and the Sir4
      interacting domain of IN was demonstrated by swapping these motifs and showing
      that the chimeric IN and Esc1 proteins effectively target integration and
      partition DNA, respectively. We conclude that Ty5 targets integration by
      imitating the Esc1-Sir4 interaction and suggest molecular mimicry as a general
      mechanism that enables mobile elements to interface with cellular processes.

PMID- 18086892
TI  - Spn1 regulates the recruitment of Spt6 and the Swi/Snf complex during
      transcriptional activation by RNA polymerase II.
AB  - We investigated the timing of the recruitment of Spn1 and its partner, Spt6, to
      the CYC1 gene. Like TATA binding protein and RNA polymerase II (RNAPII), Spn1 is
      constitutively recruited to the CYC1 promoter, although levels of transcription
      from this gene, which is regulated postrecruitment of RNAPII, are low. In
      contrast, Spt6 appears only after growth in conditions in which the gene is
      highly transcribed. Spn1 recruitment is via interaction with RNAPII, since an
      spn1 mutant defective for interaction with RNAPII is not targeted to the
      promoter, and Spn1 is necessary for Spt6 recruitment. Through a targeted genetic
      screen, strong and specific antagonizing interactions between SPN1 and genes
      encoding Swi/Snf subunits were identified. Like Spt6, Swi/Snf appears at CYC1
      only after activation of the gene. However, Spt6 significantly precedes Swi/Snf
      occupancy at the promoter. In the absence of Spn1 recruitment, Swi/Snf is
      constitutively found at the promoter. These observations support a model whereby
      Spn1 negatively regulates RNAPII transcriptional activity by inhibiting
      recruitment of Swi/Snf to the CYC1 promoter, and this inhibition is abrogated by
      the Spn1-Spt6 interaction. These findings link Spn1 functions to the transition
      from an inactive to an actively transcribing RNAPII complex at a postrecruitment
      regulated promoter.

PMID- 18086893
TI  - Regulation of neuron-specific alternative splicing of neurofibromatosis type 1
      pre-mRNA.
AB  - Neurofibromatosis type 1 (NF1) is one of the most common heritable autosomal
      dominant disorders. Alternative splicing modulates the function of neurofibromin,
      the NF1 gene product, by inserting the in-frame exon 23a into the region of NF1
      mRNA that encodes the GTPase-activating protein-related domain. This insertion,
      which is predominantly skipped in neurons, reduces the ability of neurofibromin
      to regulate Ras by 10-fold. Here, we report that the neuron-specific Hu proteins
      control the production of the short protein isoform by suppressing inclusion of
      NF1 exon 23a, while TIA-1/TIAR proteins promote inclusion of this exon. We
      identify two binding sites for Hu proteins, located upstream and downstream of
      the regulated exon, and provide biochemical evidence that Hu proteins
      specifically block exon definition by preventing binding of essential splicing
      factors. In vitro analyses using nuclear extracts show that at the downstream
      site, Hu proteins prevent binding of U1 and U6 snRNPs to the 5' splice site,
      while TIAR increases binding. Hu proteins also decrease U2AF binding at the 3'
      splice site located upstream of exon 23a. In addition to providing the first
      mechanistic insight into tissue-specific control of NF1 splicing, these studies
      establish a novel strategy whereby Hu proteins regulate RNA processing.

PMID- 18086894
TI  - Up-regulation of P-TEFb by the MEK1-extracellular signal-regulated kinase
      signaling pathway contributes to stimulated transcription elongation of immediate
      early genes in neuroendocrine cells.
AB  - The positive elongation factor P-TEFb appears to function as a crucial C-terminal
      domain (CTD) kinase for RNA polymerase II (Pol II) transcribing immediate early
      genes (IEGs) in neuroendocrine GH4C1 cells. Chromatin immunoprecipitation
      indicated that in resting cells Pol II occupied the promoter-proximal regions of
      the c-fos and junB genes, together with the negative elongation factors DSIF and
      NELF. Thyrotropin-releasing hormone (TRH)-induced recruitment of positive
      transcription elongation factor b (P-TEFb) abolished the pausing of Pol II and
      enhanced phosphorylation of CTD serine 2, resulting in transcription elongation.
      In addition, P-TEFb was essential for splicing and 3'-end processing of IEG
      transcripts. Importantly, the MEK1-extracellular signal-regulated kinase (ERK)
      signaling pathway activated by TRH up-regulated nuclear CDK9 and CDK9/cyclinT1
      dimers (i.e., P-TEFb), facilitating the recruitment of P-TEFb to c-fos and other
      IEGs. Thus, in addition to established gene transcription control via promoter
      response elements, the MEK1-ERK signaling pathway controls transcription
      elongation by Pol II via the up-regulation of nuclear CDK9 integrated into P
      TEFb.

PMID- 18086895
TI  - Corepressor CtBP and nuclear speckle protein Pnn/DRS differentially modulate
      transcription and splicing of the E-cadherin gene.
AB  - CtBP is a transcriptional corepressor with tumorigenic potential that targets the
      promoter of the tumor suppressor gene E-cadherin. Pnn/DRS (Pnn) is a "nuclear
      speckle"-associated protein involved in mRNA processing as well as
      transcriptional regulation of E-cadherin via its binding to CtBP. Here, we show
      that CtBP can recruit Pnn to CtBP-associated complexes, resulting in Pnn
      dependent chromatin remodeling at the E-cadherin promoter. In addition, CtBP and
      Pnn can differentially modulate E-cadherin mRNA splicing, with polymerase II
      serving as an interface in this event. Therefore, the Pnn/CtBP functional
      interplay represents a novel mechanism linking the corepressor CtBP and Pnn to
      the transcription-coupled mRNA splicing of a major tumor suppressor gene. Our
      findings implicate the existence of the molecular switches involved in
      tumorigenesis, which coordinate promoter-specific events and mRNA processing, by
      serving as bridging elements between the regulatory complexes both at gene
      promoters and within the mRNA splicing machineries.

PMID- 18086896
TI  - DOG-1 is the Caenorhabditis elegans BRIP1/FANCJ homologue and functions in
      interstrand cross-link repair.
AB  - Fanconi anemia (FA) is a cancer susceptibility syndrome characterized by
      defective DNA interstrand cross-link (ICL) repair. Here, we show that DOG-1 is
      the Caenorhabditis elegans homologue of FANCJ, a helicase mutated in FA-J
      patients. DOG-1 performs a conserved role in ICL repair, as dog-1 mutants are
      hypersensitive to ICL-inducing agents, but not to UVC irradiation or X rays.
      Genetic analysis indicated that dog-1 is epistatic with fcd-2 (C. elegans FANCD2)
      but is nonepistatic with brc-1 (C. elegans BRCA1), thus establishing the
      existence of two distinct pathways of ICL repair in worms. Furthermore, DOG-1 is
      dispensable for FCD-2 and RAD-51 focus formation, suggesting that DOG-1 operates
      downstream of FCD-2 and RAD-51 in ICL repair. DOG-1 was previously implicated in
      poly(G)/poly(C) (G/C) tract maintenance during DNA replication. G/C tracts remain
      stable in the absence of ATL-1, CLK-2 (FA pathway activators), FCD-2, BRC-2, and
      MLH-1 (associated FA components), implying that DOG-1 is the sole FA component
      required for G/C tract maintenance in a wild-type background. However, FCD-2 is
      required to promote deletion-free repair at G/C tracts in dog-1 mutants,
      consistent with a role for FA factors at the replication fork. The functional
      conservation between DOG-1 and FANCJ suggests a possible role for FANCJ in G/C
      tract maintenance in human cells.

PMID- 18086897
TI  - Mitochondrial Iba57p is required for Fe/S cluster formation on aconitase and
      activation of radical SAM enzymes.
AB  - A genome-wide screen for Saccharomyces cerevisiae iron-sulfur (Fe/S) cluster
      assembly mutants identified the gene IBA57. The encoded protein Iba57p is located
      in the mitochondrial matrix and is essential for mitochondrial DNA maintenance.
      The growth phenotypes of an iba57Delta mutant and extensive functional studies in
      vivo and in vitro indicate a specific role for Iba57p in the maturation of
      mitochondrial aconitase-type and radical SAM Fe/S proteins (biotin and lipoic
      acid synthases). Maturation of other Fe/S proteins occurred normally in the
      absence of Iba57p. These observations identify Iba57p as a novel dedicated
      maturation factor with specificity for a subset of Fe/S proteins. The Iba57p
      primary sequence is distinct from any known Fe/S assembly factor but is similar
      to certain tetrahydrofolate-binding enzymes, adding a surprising new function to
      this protein family. Iba57p physically interacts with the mitochondrial ISC
      assembly components Isa1p and Isa2p. Since all three proteins are conserved in
      eukaryotes and bacteria, the specificity of the Iba57/Isa complex may represent a
      biosynthetic concept that is universally used in nature. In keeping with this
      idea, the human IBA57 homolog C1orf69 complements the iba57Delta growth defects,
      demonstrating its conserved function throughout the eukaryotic kingdom.

PMID- 18086898
TI  - Blocking of monocyte-associated B7-H1 (CD274) enhances HCV-specific T cell
      immunity in chronic hepatitis C infection.
AB  - The establishment of a chronic hepatitis C (CHC) infection is associated with
      defective HCV-specific T cell responses. Recent studies suggest that negative T
      cell regulators such as programmed death 1 (PD-1) contribute to the impairment of
      virus-specific T cell functions in chronic viral infections. However, the
      implication of peripheral monocytes from CHC patients in the inhibition of HCV
      specific T cell responses is only partially defined. In this study, we found that
      B7-H1, a ligand of PD-1, was significantly up-regulated on monocytes of CHC
      patients. Proliferation of T cells in response to anti-CD3 antibody was directly
      suppressed by B7-H1+CD14+ monocytes, and this suppression was reversed by
      addition of antagonistic B7-H1 mAb. Furthermore, blocking of monocyte-associated
      B7-H1 (moB7-H1) significantly enhanced the frequency of IFN-gamma-producing, HCV
      specific CD4+ and CD8+ effector T cells and the production of Th1 cytokines, such
      as IL-2 but not Th2 cytokines, including IL-4 and IL-10. Upon B7-H1 blockade,
      production of perforin was also increased in CD8+ T cells stimulated with HCV
      peptides. Our findings suggest that moB7-H1 inhibits HCV-specific CD4+ and CD8+ T
      lymphocyte proliferation and suppresses Th1 cytokine production and perforin
      secretion. Blockade of the B7-H1 pathway thus represents an attractive approach
      in the treatment of chronic HCV infection.

PMID- 18086899
TI  - Phenotypic differences between healthy effector CTL and leukemic LGL cells
      support the notion of antigen-triggered clonal transformation in T-LGL leukemia.
AB  - T cell large granular lymphocyte leukemia (T-LGL) is a chronic clonal
      lymphoproliferation of CTL. In many ways, T-LGL clones resemble terminal effector
      CTL, including down-modulation of CD28 and overexpression of perforin, granzymes,
      and CD57. We studied the transcriptome of T-LGL clones and compared it with
      healthy CD8+CD57+ effector cells as well as CD8+CD57- populations. T-LGL clones
      were sorted based on their TCR variable beta-chain restriction, and controls were
      obtained by pooling cell populations from 14 donors. Here, we focus our analysis
      on immunological networks, as immune mechanisms play a prominent role in the
      etiology of bone marrow failure in T-LGL. Informative genes identified by
      expression arrays were studied further in an independent cohort of patients using
      Taqman PCR, ELISA assays, and FACS analysis. Despite a strikingly similar gene
      expression profile between T-LGL clones and their healthy counterparts, important
      phenotypic differences were identified, including up-modulation of TNFRS9,
      myeloid cell leukemia sequence 1, IFN-gamma, and IFN-gamma-related genes, and
      several integrins/adhesion molecules. In addition, T-LGL clones were
      characterized by an overexpression of chemokines and chemokine receptors that are
      typically associated with viral infections (CXCL2, Hepatitis A virus cellular
      receptor 1, IL-18, CCR2). Our studies suggest that immunodominant LGL clones,
      although phenotypically similar to effector CTL, show significantly altered
      expression of a number of genes, including those associated with an ongoing viral
      infection or chronic, antigen-driven immune response.

PMID- 18086900
TI  - In vitro hyperglycemia or a diabetic intrauterine environment reduces neonatal
      endothelial colony-forming cell numbers and function.
AB  - OBJECTIVE: Emerging data demonstrate that maternal diabetes has long-term health
      consequences for offspring, including the development of hypertension. In adults,
      circulating endothelial progenitor cells (EPCs) participate in vascular repair,
      and EPC numbers and function inversely correlate with the risk of developing
      vascular disease. Therefore, our objectives were to determine whether
      hyperglycemia or exposure to a diabetic intrauterine environment alters EPC
      function. RESEARCH DESIGN AND METHODS: We used well-established clonogenic
      endothelial colony-forming cell (ECFC) assays and murine transplantation
      experiments to examine human vasculogenesis. RESULTS: Both in vitro hyperglycemia
      and a diabetic intrauterine environment reduced ECFC colony formation, self
      renewal capacity, and capillary-like tube formation in matrigel. This cellular
      phenotype was linked to premature senescence and reduced proliferation. Further,
      cord blood ECFCs from diabetic pregnancies formed fewer chimeric vessels de novo
      after transplantation into immunodeficient mice compared with neonatal ECFCs
      harvested from uncomplicated pregnancies. CONCLUSIONS; Collectively, these data
      demonstrate that hyperglycemia or exposure to a diabetic intrauterine environment
      diminishes neonatal ECFC function both in vitro and in vivo, providing potential
      mechanistic insights into the long-term cardiovascular complications observed in
      newborns of diabetic pregnancies.

PMID- 18086901
TI  - Reversal of streptozotocin-induced diabetes in mice by cellular transduction with
      recombinant pancreatic transcription factor pancreatic duodenal homeobox-1: a
      novel protein transduction domain-based therapy.
AB  - OBJECTIVE: The key pancreatic transcription factor pancreatic duodenal homeobox-1
      (Pdx1), known to control development and maintenance of pancreatic beta-cells,
      possesses a protein transduction domain (PTD) that facilitates its entry into
      cells. We therefore sought to evaluate the capacity of in vivo-administered
      recombinant Pdx1 (rPdx1) to ameliorate hyperglycemia in mice with streptozotocin
      induced diabetes. RESEARCH DESIGN AND METHODS: Cell entry and transcriptional
      regulatory properties of rPdx1 protein and its PTD-deletion mutant rPdx1Delta
      protein, as well as a PTD-green fluorescent protein, were evaluated in vitro.
      After intraperitoneal rPdx1 injection into mice with streptozotocin-induced
      diabetes, we assessed its action on blood glucose levels, insulin content,
      intraperitoneal glucose tolerance test (IPGTT), Pdx1 distribution, pancreatic
      gene expression, islet cell proliferation, and organ histology. RESULTS:
      Restoration of euglycemia in Pdx1-treated diabetic mice was evident by improved
      IPGTT and glucose-stimulated insulin release. Insulin, glucagon, and Ki67
      immunostaining revealed increased islet cell number and proliferation in
      pancreata of rPdx1-treated mice. Real-time PCR of pancreas and liver demonstrated
      upregulation of INS and PDX1 genes and other genes relevant to pancreas
      regeneration. While the time course of beta-cell gene expression and serum/tissue
      insulin levels indicated that both liver- and pancreas-derived insulin
      contributed to restoration of normoglycemia, near-total pancreatectomy resulted
      in hyperglycemia, suggesting that beta-cell regeneration played the primary role
      in rPdx1-induced glucose homeostasis. CONCLUSIONS: rPdx1 treatment of mice with
      streptozotocin-induced diabetes promotes beta-cell regeneration and liver cell
      reprogramming, leading to restoration of normoglycemia. This novel PTD-based
      protein therapy offers a promising way to treat patients with diabetes while
      avoiding potential side effects associated with the use of viral vectors.

PMID- 18086902
TI  - Retinal arteriolar narrowing predicts incidence of diabetes: the Australian
      Diabetes, Obesity and Lifestyle (AusDiab) Study.
AB  - OBJECTIVE: To examine the relationship of retinal vascular caliber to incident
      diabetes in a population-based cohort. RESEARCH DESIGN AND METHODS: The
      Australian Diabetes, Obesity and Lifestyle (AusDiab) Study recruited adults aged
      25+ years across Australia in 1999-2000, with a follow-up 5 years later in 2004
      2005. Participants' glycemic status was classified using fasting plasma glucose
      (FPG) and 2-h oral glucose tolerance (2-h plasma glucose [2hPG]) tests. Diabetes
      was diagnosed if FPG was >or=7.0 mmol/l or 2hPG was >or=11.1 mmol/l. Retinal
      vascular caliber was measured from baseline retinal photographs using a computer
      assisted program. RESULTS: Of the 803 participants without diabetes at baseline,
      108 (13.4%) developed diabetes at follow-up: 7 (2.8%) of 246 participants with
      normal glucose tolerance, 9 (13.6%) of 66 participants with impaired fasting
      glucose, and 92 (18.7%) of 491 participants with impaired glucose tolerance.
      After multivariate analysis, participants with narrower retinal arteriolar
      caliber had a higher risk of diabetes (odds ratio 2.21 [95% CI 1.02-4.80],
      comparing smallest versus highest arteriolar caliber tertiles, P = 0.04 for
      trend). There was no association between retinal venular caliber and incident
      diabetes. CONCLUSIONS: Narrower retinal arteriolar caliber predicted risk of
      diabetes. These data provide further evidence that microvascular changes may
      contribute to the pathogenesis of diabetes.

PMID- 18086903
TI  - Synergy between leptin therapy and a seemingly negligible amount of voluntary
      wheel running prevents progression of dietary obesity in leptin-resistant rats.
AB  - OBJECTIVE: We examined whether chronic leptin treatment of diet-induced obese
      rats promotes or alleviates the susceptibility to continued high-fat feeding.
      Second, we examined if voluntary wheel running is beneficial in reducing the
      trajectory of weight gain in high-fat-raised leptin-resistant rats. RESEARCH
      DESIGN AND METHODS: Sprague-Dawley rats were fed a standard diet or a high-fat
      diet for 5 months, and then hypothalamic leptin overexpression was induced
      through central administration of adeno-associated virus-encoding leptin while
      continuing either the standard or high-fat diet. Two weeks later, half of the
      rats in each group were provided access to running wheels for 38 days while being
      maintained on either a standard or high-fat diet. RESULTS; In standard diet
      raised rats, either wheel running or leptin reduced the trajectory of weight
      gain, and the combined effect of both treatments was additive. In high-fat-raised
      leptin-resistant rats, leptin overexpression first transiently reduced weight
      gain but then accelerated the weight gain twofold over controls. Wheel running in
      high-fat-raised rats was sixfold less than in standard diet-raised rats and did
      not affect weight gain. Surprisingly, wheel running plus leptin completely
      prevented weight gain. This synergy was associated with enhanced hypothalamic
      signal transducer and activator of transcription (STAT) 3 phosphorylation and
      suppressor of cytokine signaling 3 expression in wheel running plus leptin
      compared with leptin-treated sedentary high-fat counterparts. This enhanced STAT3
      signaling associated with the combination treatment occurred only in high-fat
      raised, leptin-resistant rats and not in standard diet-raised, leptin-responsive
      rats. CONCLUSIONS: Chronic leptin treatment in diet-induced obese rats
      accelerates dietary obesity. However, leptin combined with wheel running prevents
      further dietary weight gain. Thus, this combination therapy may be a viable
      antiobesity treatment.

PMID- 18086904
TI  - Protein kinase C theta activation induces insulin-mediated constriction of muscle
      resistance arteries.
AB  - OBJECTIVE: Protein kinase C (PKC) theta activation is associated with insulin
      resistance and obesity, but the underlying mechanisms have not been fully
      elucidated. Impairment of insulin-mediated vasoreactivity in muscle contributes
      to insulin resistance, but it is unknown whether PKC theta is involved. In this
      study, we investigated whether PKC theta activation impairs insulin-mediated
      vasoreactivity and insulin signaling in muscle resistance arteries. RESEARCH
      DESIGN AND METHODS: Vasoreactivity of isolated resistance arteries of mouse
      gracilis muscles to insulin (0.02-20 nmol/l) was studied in a pressure myograph
      with or without PKC theta activation by palmitic acid (PA) (100 micromol/l).
      RESULTS: In the absence of PKC theta activation, insulin did not alter arterial
      diameter, which was caused by a balance of nitric oxide-dependent vasodilator and
      endothelin-dependent vasoconstrictor effects. Using three-dimensional microscopy
      and Western blotting of muscle resistance arteries, we found that PKC theta is
      abundantly expressed in endothelium of muscle resistance arteries of both mice
      and humans and is activated by pathophysiological levels of PA, as indicated by
      phosphorylation at Thr(538) in mouse resistance arteries. In the presence of PA,
      insulin induced vasoconstriction (21 +/- 6% at 2 nmol/l insulin), which was
      abolished by pharmacological or genetic inactivation of PKC theta. Analysis of
      intracellular signaling in muscle resistance arteries showed that PKC theta
      activation reduced insulin-mediated Akt phosphorylation (Ser(473)) and increased
      extracellular signal-related kinase (ERK) 1/2 phosphorylation. Inhibition of PKC
      theta restored insulin-mediated vasoreactivity and insulin-mediated activation of
      Akt and ERK1/2 in the presence of PA. CONCLUSIONS: PKC theta activation induces
      insulin-mediated vasoconstriction by inhibition of Akt and stimulation of ERK1/2
      in muscle resistance arteries. This provides a new mechanism linking PKC theta
      activation to insulin resistance.

PMID- 18086905
TI  - Arthroscopic synovectomy in rheumatoid arthritis of wrist.
AB  - The wrist is the most commonly involved region of the upper extremity in
      rheumatoid arthritis (RA). Because the wrist joint becomes involved early during
      the disease course and its involvement rapidly progresses, and because the
      disabilities associated with progressive RA are significant, early and adequate
      treatment must be introduced to prevent disease progression. Various treatment
      methods can be employed to treat RA wrists based on radiological and clinical
      findings. Arthroscopic synovectomy is recommended for pain relief and functional
      recovery in early stage RA, and is also helpful in advanced staged RA with Larsen
      stage III. However, arthroscopic synovectomy is not recommended as an effective
      method of treatment for all patients with advanced radiographic changes.
      Nevertheless, arthroscopic synovectomy may delay the need for complex surgery,
      such as wrist arthrodesis or total wrist arthroplasty in selective cases.
      Although arthroscopic synovectomy of the wrist cannot improve grip strength or
      range of motion, it can reduce wrist pain and improve function, and thus
      facilitate return to work.

PMID- 18086906
TI  - Percutaneous closure of patent foramen ovale: a case series and literature
      review.
AB  - Patent foramen ovale (PFO) is an anatomical variant of the interatrial septum
      with an overall prevalence of 27% in autopsy studies. PFOs have a potential role
      in causation of stroke, platypneaorthodeoxia, decompression sickness, right to
      left shunt and migraine headaches. Data regarding percutaneous closure of PFO in
      low volume tertiary care centers is lacking. Retrospective review of 14
      percutaneous PFO closures done in our facility from March 2005 to August 2006 was
      performed for efficacy of procedure and safety. All patients received clopidogrel
      for a period of 3 months, and aspirin and subacute bacterial endocarditis
      prophylaxis for 6 months. Mean age of the study population was 54 years. Fifty
      percent (7 of 14) of patients experienced an atrial septal aneurysm and 14% (2
      patients) exhibited a hypercoagulable state. The indication for closure in 13
      patients was transient ischemic attacks or strokes, while one patient had
      persistent hypoxia due to a severe right to left shunt at PFO. Patients received
      either a CardioSEAL or Amplatzer device. Deployment rate was 100%. All patients
      completed a minimum of 6 months of follow-up, with a mean follow-up time of 14.9
      +/- 7.6 months. No immediate or late bleeding complication occurred in any
      patient. One patient developed paroxysmal atrial fibrillation and one patient
      developed thrombotic complications at 7 months post-procedure secondary to the
      progression of her anal carcinoma and subsequently died. Pending the results of
      the four large randomized trials that are enrolling patients, percutaneous
      closure of PFO for cryptogenic strokes is an attractive alternative to lifelong
      anticoagulation with relatively few complications, even in low volume centers.
      There are many challenges in the management of this subset of patients, the
      foremost being the selection of a target patient population. Role of PFO in
      migraines is less clear.

PMID- 18086908
TI  - Human papillomavirus infections in primary care.
AB  - Cervical cancer continues to be a leading cause of mortality worldwide. The
      incidence and mortality associated with invasive cervical cancer have declined
      significantly in developed countries due to widespread availability of screening
      with the Papanicolaou (Pap) test. However, the incidence and prevalence of non
      invasive cervical intraepithelial neoplasms and genital warts related to
      oncogenic and nononcogenic strains of human papilloma viruses (HPV) have remained
      relatively stable. Recent advances in molecular diagnostics have resulted in
      improved characterization of various HPV types and have led to changes in
      terminology of Pap test findings. Changes in nomenclature may lead to confusion
      among primary care providers regarding how best to further evaluate abnormal
      cytological results. This article provides a concise overview of the approach to
      the treatment of genital warts and management of abnormal cervical cytology based
      on guidelines from the American Society of Colposcopy and Cervical Pathology. It
      also reviews advances in HPV vaccine development and the new recombinant vaccine
      recently approved for use in the United States.

PMID- 18086907
TI  - Tumor-related hyponatremia.
AB  - Hyponatremia is an important and common electrolyte disorder in tumor patients
      and one that has been reported in association with a number of different primary
      diagnoses. The correct diagnosis of the pathophysiological basis for each patient
      is important because it significantly alters the treatment approach. In this
      article, we review the epidemiology and presentation of patients with
      hyponatremia, the pathophysiologic groups for the disorder with respect to sodium
      and water balance and the diagnostic measures for determining the correct
      pathophysiologic groups. We then present the various treatment options based on
      the pathophysiologic groups including a mathematical approach to the use of
      hypertonic saline in management. In cancer patients, hyponatremia is a serious
      comorbidity that requires particular attention as its treatment varies by
      pathophysiologic groups, and its consequences can have a deleterious effect on
      the patient's health.

PMID- 18086909
TI  - Gilbert Weidinger: regeneration researcher. Interviewed by Ruth Williams.

PMID- 18086910
TI  - Show me the data.

PMID- 18086911
TI  - Drosophila TIF-IA is required for ribosome synthesis and cell growth and is
      regulated by the TOR pathway.
AB  - Synthesis of ribosomal RNA (rRNA) is a key step in ribosome biogenesis and is
      essential for cell growth. Few studies, however, have investigated rRNA synthesis
      regulation in vivo in multicellular organisms. Here, we present a genetic
      analysis of transcription initiation factor IA (TIF-IA), a conserved RNA
      polymerase I transcription factor. Drosophila melanogaster Tif-IA(-/-) mutants
      have reduced levels of rRNA synthesis and sustain a developmental arrest caused
      by a block in cellular growth. We find that the target of rapamycin (TOR) pathway
      regulates TIF-IA recruitment to rDNA. Furthermore, we show that the TOR pathway
      regulates rRNA synthesis in vivo and that TIF-IA overexpression can maintain rRNA
      transcription when TOR activity is reduced in developing larvae. We propose that
      TIF-IA acts in vivo as a downstream growth-regulatory target of the TOR pathway.
      Overexpression of TIF-IA also elevates levels of both 5S RNA and messenger RNAs
      encoding ribosomal proteins. Stimulation of rRNA synthesis by TIF-IA may
      therefore provide a feed-forward mechanism to coregulate the levels of other
      ribosome components.

PMID- 18086912
TI  - Dimeric PKD regulates membrane fission to form transport carriers at the TGN.
AB  - Protein kinase D (PKD) is recruited to the trans-Golgi network (TGN) through
      interaction with diacylglycerol (DAG) and is required for the biogenesis of TGN
      to cell surface transport carriers. We now provide definitive evidence that PKD
      has a function in membrane fission. PKD depletion by siRNA inhibits trafficking
      from the TGN, whereas expression of a constitutively active PKD converts TGN into
      small vesicles. These findings demonstrate that PKD regulates membrane fission
      and this activity is used to control the size of transport carriers, and to
      prevent uncontrolled vesiculation of TGN during protein transport.

PMID- 18086913
TI  - PDZRhoGEF and myosin II localize RhoA activity to the back of polarizing
      neutrophil-like cells.
AB  - Chemoattractants such as formyl-Met-Leu-Phe (fMLP) induce neutrophils to polarize
      by triggering divergent pathways that promote formation of a protrusive front and
      contracting back and sides. RhoA, a Rho GTPase, stimulates assembly of actomyosin
      contractile complexes at the sides and back. We show here, in differentiated HL60
      cells, that PDZRhoGEF (PRG), a guanine nucleotide exchange factor (GEF) for RhoA,
      mediates RhoA-dependent responses and determines their spatial distribution. As
      with RNAi knock-down of PRG, a GEF-deleted PRG mutant blocks fMLP-dependent RhoA
      activation and causes neutrophils to exhibit multiple fronts and long tails.
      Similarly, inhibition of RhoA, a Rho-dependent protein kinase (ROCK), or myosin
      II produces the same morphologies. PRG inhibition reduces or mislocalizes
      monophosphorylated myosin light chains in fMLP-stimulated cells, and myosin II
      ATPase inhibition reciprocally disrupts normal localization of PRG. We propose a
      cooperative reinforcing mechanism at the back of cells, in which PRG, RhoA, ROCK,
      myosin II, and actomyosin spatially cooperate to consolidate attractant-induced
      contractility and ensure robust cell polarity.

PMID- 18086914
TI  - The mitochondrial respiratory chain is a modulator of apoptosis.
AB  - Mitochondrial dysfunction and dysregulation of apoptosis are implicated in many
      diseases such as cancer and neurodegeneration. We investigate here the role of
      respiratory chain (RC) dysfunction in apoptosis, using mitochondrial DNA
      mutations as genetic models. Although some mutations eliminate the entire RC,
      others target specific complexes, resulting in either decreased or complete loss
      of electron flux, which leads to impaired respiration and adenosine triphosphate
      (ATP) synthesis. Despite these similarities, significant differences in responses
      to apoptotic stimuli emerge. Cells lacking RC are protected against both
      mitochondrial- and endoplasmic reticulum (ER) stress-induced apoptosis. Cells
      with RC, but unable to generate electron flux, are protected against
      mitochondrial apoptosis, although they have increased sensitivity to ER stress.
      Finally, cells with a partial reduction in electron flux have increased apoptosis
      under both conditions. Our results show that the RC modulates apoptosis in a
      context-dependent manner independent of ATP production and that apoptotic
      responses are the result of the interplay between mitochondrial functional state
      and environmental cues.

PMID- 18086915
TI  - Interaction of the conserved oligomeric Golgi complex with t-SNARE
      Syntaxin5a/Sed5 enhances intra-Golgi SNARE complex stability.
AB  - Tethering factors mediate initial interaction of transport vesicles with target
      membranes. Soluble N-ethylmaleimide-sensitive fusion protein attachment protein
      receptors (SNAREs) enable consequent docking and membrane fusion. We demonstrate
      that the vesicle tether conserved oligomeric Golgi (COG) complex colocalizes and
      coimmunoprecipitates with intra-Golgi SNARE molecules. In yeast cells, the COG
      complex preferentially interacts with the SNARE complexes containing yeast Golgi
      target (t)-SNARE Sed5p. In mammalian cells, hCog4p and hCog6p interact with
      Syntaxin5a, the mammalian homologue of Sed5p. Moreover, fluorescence resonance
      energy transfer reveals an in vivo interaction between Syntaxin5a and the COG
      complex. Knockdown of the mammalian COG complex decreases Golgi SNARE mobility,
      produces an accumulation of free Syntaxin5, and decreases the steady-state levels
      of the intra-Golgi SNARE complex. Finally, overexpression of the hCog4p N
      terminal Syntaxin5a-binding domain destabilizes intra-Golgi SNARE complexes,
      disrupting the Golgi. These data suggest that the COG complex orchestrates
      vesicular trafficking similarly in yeast and mammalian cells by binding to the t
      SNARE Syntaxin5a/Sed5p and enhancing the stability of intra-Golgi SNARE
      complexes.

PMID- 18086916
TI  - A molecular specificity code for the three mammalian KDEL receptors.
AB  - AC-terminal KDEL-like motif prevents secretion of soluble endoplasmic reticulum
      (ER)-resident proteins. This motif interacts with KDEL receptors localized in the
      intermediate compartment and Golgi apparatus. Such binding triggers retrieval
      back to the ER via a coat protein I-dependent pathway. To date, two human KDEL
      receptors have been reported. Here, we report the Golgi localization of a third
      human KDEL receptor. Using a reporter construct system from a screen of 152
      variants, we identified 35 KDEL-like variants that result in efficient ER
      localization but do not match the current Prosite motif for ER localization
      ([KRHQSA]-[DENQ]-E-L). We cloned 16 human proteins with one of these motifs and
      all were found in the ER. A subsequent screen by bimolecular fluorescence
      complementation determined the specificities of the three human KDEL receptors.
      Each KDEL receptor has a unique pattern of motifs with which it interacts. This
      suggests a specificity in the retrieval of human proteins that contain different
      KDEL variants.

PMID- 18086917
TI  - A naturally occurring calcineurin variant inhibits FoxO activity and enhances
      skeletal muscle regeneration.
AB  - The calcium-activated phosphatase calcineurin (Cn) transduces physiological
      signals through intracellular pathways to influence the expression of specific
      genes. Here, we characterize a naturally occurring splicing variant of the
      CnAbeta catalytic subunit (CnAbeta1) in which the autoinhibitory domain that
      controls enzyme activation is replaced with a unique C-terminal region. The
      CnAbeta1 enzyme is constitutively active and dephosphorylates its NFAT target in
      a cyclosporine-resistant manner. CnAbeta1 is highly expressed in proliferating
      myoblasts and regenerating skeletal muscle fibers. In myoblasts, CnAbeta1
      knockdown activates FoxO-regulated genes, reduces proliferation, and induces
      myoblast differentiation. Conversely, CnAbeta1 overexpression inhibits FoxO and
      prevents myotube atrophy. Supplemental CnAbeta1 transgene expression in skeletal
      muscle leads to enhanced regeneration, reduced scar formation, and accelerated
      resolution of inflammation. This unique mode of action distinguishes the CnAbeta1
      isoform as a candidate for interventional strategies in muscle wasting treatment.

PMID- 18086918
TI  - MyD88-deficient bone marrow cells accelerate onset and reduce survival in a mouse
      model of amyotrophic lateral sclerosis.
AB  - Increasing evidence suggests that neurotoxicity of secreted superoxide dismutase
      1 (SOD1) mutants is associated with amyotrophic lateral sclerosis (ALS). We show
      here that mutant SOD1 protein activates microglia via a myeloid differentiation
      factor 88 (MyD88)-dependent pathway. This inflammatory response is also
      associated with a marked recruitment of bone marrow-derived microglia (BMDM) in
      the central nervous system. We then generated chimeric SOD1(G37R) and SOD1(G93A)
      mice by transplantation of bone marrow (BM) cells from MyD88-deficient or green
      fluorescent protein (GFP)-expressing mice. SOD1(G37R) mice receiving MyD88(-/-)
      BM cells exhibit a significantly earlier disease onset and shorter lifespan
      compared with mice transplanted with control GFP cells. This compelling
      beneficial effect of MyD88-competent BMDM is a previously unrecognized natural
      innate immune mechanism of neuroprotection in a mouse model of late-onset motor
      neuron disease.

PMID- 18086919
TI  - Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in
      the adult subventricular zone.
AB  - We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural
      progenitor cells during postnatal development. Chondroitin sulfate proteoglycan
      (NG2)-expressing progenitor cells of the subventricular zone (SVZ) show no
      significant difference in density and proliferation between Cdk2(-/-) and wild
      type mice at perinatal ages and are reduced only in adult Cdk2(-/-) mice. Adult
      Cdk2(-/-) SVZ cells in culture display decreased self-renewal capacity and
      enhanced differentiation. Compensatory mechanisms in perinatal Cdk2(-/-) SVZ
      cells, which persist until postnatal day 15, involve increased Cdk4 expression
      that results in retinoblastoma protein inactivation. A subsequent decline in Cdk4
      activity to wild-type levels in postnatal day 28 Cdk2(-/-) cells coincides with
      lower NG2+ proliferation and self-renewal capacity similar to adult levels. Cdk4
      silencing in perinatal Cdk2(-/-) SVZ cells abolishes Cdk4 up-regulation and
      reduces cell proliferation and self- renewal to adult levels. Conversely, Cdk4
      overexpression in adult SVZ cells restores proliferative capacity to wild-type
      levels. Thus, although Cdk2 is functionally redundant in perinatal SVZ, it is
      important for adult progenitor cell proliferation and self-renewal through age
      dependent regulation of Cdk4.

PMID- 18086920
TI  - EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma
      cells.
AB  - Lamellipodial protrusion and directional migration of carcinoma cells towards
      chemoattractants, such as epidermal growth factor (EGF), depend upon the spatial
      and temporal regulation of actin cytoskeleton by actin-binding proteins (ABPs).
      It is generally hypothesized that the activity of many ABPs are temporally and
      spatially regulated by PIP(2); however, this is mainly based on in vitro-binding
      and structural studies, and generally in vivo evidence is lacking. Here, we
      provide the first in vivo data that directly visualize the spatial and temporal
      regulation of cofilin by PIP(2) in living cells. We show that EGF induces a rapid
      loss of PIP(2) through PLC activity, resulting in a release and activation of a
      membrane-bound pool of cofilin. Upon release, we find that cofilin binds to and
      severs F-actin, which is coincident with actin polymerization and lamellipod
      formation. Moreover, our data provide evidence for how PLC is involved in the
      formation of protrusions in breast carcinoma cells during chemotaxis and
      metastasis towards EGF.

PMID- 18086921
TI  - Newly identified biologically active and proteolysis-resistant VEGF-A isoform
      VEGF111 is induced by genotoxic agents.
AB  - Ultraviolet B and genotoxic drugs induce the expression of a vascular endothelial
      growth factor A (VEGF-A) splice variant (VEGF111) encoded by exons 1-4 and 8 in
      many cultured cells. Although not detected in a series of normal human and mouse
      tissue, VEGF111 expression is induced in MCF-7 xenografts in nude mice upon
      treatment by camptothecin. The skipping of exons that contain proteolytic
      cleavage sites and extracellular matrix-binding domains makes VEGF111 diffusible
      and resistant to proteolysis. Recombinant VEGF111 activates VEGF receptor 2 (VEGF
      R2) and extracellularly regulated kinase 1/2 in human umbilical vascular
      endothelial cells and porcine aortic endothelial cells expressing VEGF-R2. The
      mitogenic and chemotactic activity and VEGF111's ability to promote vascular
      network formation during embyonic stem cell differentiation are similar to those
      of VEGF121 and 165. Tumors in nude mice formed by HEK293 cells expressing VEGF111
      develop a more widespread network of numerous small vessels in the peritumoral
      tissue than those expressing other isoforms. Its potent angiogenic activity and
      remarkable resistance to proteolysis makes VEGF111 a potential adverse factor
      during chemotherapy but a beneficial therapeutic tool for ischemic diseases.

PMID- 18086922
TI  - Phosphorylation at S365 is a gatekeeper event that changes the structure of Cx43
      and prevents down-regulation by PKC.
AB  - Phosphorylation at unspecified sites is known to regulate the life cycle
      (assembly, gating, and turnover) of the gap junction protein, Cx43. In this
      paper, we show that Cx43 is phosphorylated on S365 in cultured cells and heart
      tissue. Nuclear magnetic resonance structural studies of the C-terminal region of
      Cx43 with an S365D mutation indicate that it forms a different stable
      conformation than unphosphorylated wild-type Cx43. Immunolabeling with an
      antibody specific for Cx43 phosphorylated at S365 shows staining on gap junction
      structures in heart tissue that is lost upon hypoxia when Cx43 is no longer
      specifically localized to the intercalated disk. Efficient phosphorylation at
      S368, an important Cx43 channel regulatory event that increases during ischemia
      or PKC activation, depends on S365 being unphosphorylated. Thus, phosphorylation
      at S365 can serve a "gatekeeper" function that may represent a mechanism to
      protect cells from ischemia and phorbol ester-induced down-regulation of channel
      conductance.

PMID- 18086923
TI  - Myofibroblast contraction activates latent TGF-beta1 from the extracellular
      matrix.
AB  - The conjunctive presence of mechanical stress and active transforming growth
      factor beta1 (TGF-beta1) is essential to convert fibroblasts into contractile
      myofibroblasts, which cause tissue contractures in fibrotic diseases. Using
      cultured myofibroblasts and conditions that permit tension modulation on the
      extracellular matrix (ECM), we establish that myofibroblast contraction functions
      as a mechanism to directly activate TGF-beta1 from self-generated stores in the
      ECM. Contraction of myofibroblasts and myofibroblast cytoskeletons prepared with
      Triton X-100 releases active TGF-beta1 from the ECM. This process is inhibited
      either by antagonizing integrins or reducing ECM compliance and is independent
      from protease activity. Stretching myofibroblast-derived ECM in the presence of
      mechanically apposing stress fibers immediately activates latent TGF-beta1. In
      myofibroblast-populated wounds, activation of the downstream targets of TGF-beta1
      signaling Smad2/3 is higher in stressed compared to relaxed tissues despite
      similar levels of total TGF-beta1 and its receptor. We propose activation of TGF
      beta1 via integrin-mediated myofibroblast contraction as a potential checkpoint
      in the progression of fibrosis, restricting autocrine generation of
      myofibroblasts to a stiffened ECM.

PMID- 18086924
TI  - Adherence to the mediterranean diet is inversely associated with circulating
      interleukin-6 among middle-aged men: a twin study.
AB  - BACKGROUND: The Mediterranean diet is protective against cardiovascular disease;
      a proposed mechanism is through a reduction in systemic inflammation. It is
      unknown to what extent the association between the Mediterranean diet and
      inflammation is due to genetic or other familial factors. METHODS AND RESULTS: We
      administered the Willett food frequency questionnaire to 345 middle-aged male
      twins and assessed adherence to the Mediterranean diet using a published
      adherence score. Fasting plasma levels of interleukin-6, C-reactive protein, and
      known cardiovascular risk factors were measured. Mixed-effect regression analyses
      were used to examine the relationship between diet score and inflammatory
      biomarkers after accounting for known cardiovascular risk factors. Adherence to
      the Mediterranean diet was associated with reduced levels of interleukin-6
      (P<0.001) but not C-reactive protein (P=0.10) after adjustment for total energy
      intake, other nutritional factors, known cardiovascular risk factors, and use of
      supplements and medications. When the overall association of adherence to the
      diet with interleukin-6 levels was partitioned into between- and within-pair
      effects, the between-pair effect was not significant (P=0.9) and the within-pair
      effect was highly significant (P<0.0001). A 1-unit within-pair absolute
      difference in the diet score was associated with a 9% (95% CI, 4.5 to 13.6) lower
      interleukin-6 level. CONCLUSIONS: Shared environmental and genetic factors are
      unlikely to play a major role in the association between adherence to the
      Mediterranean diet and systemic inflammation. These results support the
      hypothesis that reduced inflammation is an important mechanism linking
      Mediterranean diet to reduced cardiovascular risk.

PMID- 18086925
TI  - Cardiovascular risk factors and venous thromboembolism: a meta-analysis.
AB  - BACKGROUND: The concept that venous thromboembolism (VTE) and atherosclerosis are
      2 completely distinct entities has recently been challenged because patients with
      VTE have more asymptomatic atherosclerosis and more cardiovascular events than
      control subjects. We performed a meta-analysis to assess the association between
      cardiovascular risk factors and VTE. METHODS AND RESULTS: Medline and EMBASE
      databases were searched to identify studies that evaluated the prevalence of
      major cardiovascular risk factors in VTE patients and control subjects. Studies
      were selected using a priori defined criteria, and each study was reviewed by 2
      authors who abstracted data on study characteristics, study quality, and
      outcomes. Odds ratios or weighted means and 95% confidence intervals (CIs) were
      then calculated and pooled using a random-effects model. Statistical
      heterogeneity was evaluated through the use of chi2 and I2 statistics. Twenty-one
      case-control and cohort studies with a total of 63 552 patients met the inclusion
      criteria. Compared with control subjects, the risk of VTE was 2.33 for obesity
      (95% CI, 1.68 to 3.24), 1.51 for hypertension (95% CI, 1.23 to 1.85), 1.42 for
      diabetes mellitus (95% CI, 1.12 to 1.77), 1.18 for smoking (95% CI, 0.95 to
      1.46), and 1.16 for hypercholesterolemia (95% CI, 0.67 to 2.02). Weighted mean
      high-density lipoprotein cholesterol levels were significantly lower in VTE
      patients, whereas no difference was observed for total and low-density
      lipoprotein cholesterol levels. Significant heterogeneity among studies was
      present in all subgroups except for the diabetes mellitus subgroup. Higher
      quality studies were more homogeneous, and significant associations remained
      unchanged. CONCLUSIONS: Cardiovascular risk factors are associated with VTE. This
      association is clinically relevant with respect to individual screening, risk
      factor modification, and primary and secondary prevention of VTE. Prospective
      studies should further investigate the underlying mechanisms of this
      relationship.

PMID- 18086926
TI  - Heart disease and stroke statistics--2008 update: a report from the American
      Heart Association Statistics Committee and Stroke Statistics Subcommittee.

PMID- 18086927
TI  - Radiofrequency ablation of atrial fibrillation: is the persistence of all
      intraprocedural targets necessary for long-term maintenance of sinus rhythm?
AB  - BACKGROUND: Several approaches have been developed for radiofrequency catheter
      ablation of atrial fibrillation, but the correct intraprocedural end point is
      still under debate, and few data exist about the destiny of ablation lesions over
      time. The aim of the present study was to evaluate the long-term maintenance of
      intraprocedural end points of ablation procedures. METHODS AND RESULTS: Inclusion
      criteria were (1) a previous ablation procedure of pulmonary vein (PV) encircling
      performed for drug-refractory persistent atrial fibrillation; (2) a "complete"
      intraprocedural end point, which consisted of voltage abatement inside the
      lesions, PV disconnection, and exit-block pacing from inside the lesions,
      attained in all PVs; and (3) stable sinus rhythm documented during a minimum
      follow-up of 2.5 years after the procedure. Twenty volunteers were selected (12
      males, mean age 59+/-7 years) and underwent a repeat electrophysiological study.
      After a follow-up of 36.4+/-4.7 months, complete voltage abatement was maintained
      around 32 PVs (40.0%), PV disconnection persisted in 12 (37.5%) of the previously
      isolated PVs, and exit block was present in 39 PVs (48.7%). Ten patients who
      underwent a redo ablation procedure because of recurrences of atrial fibrillation
      were used as the control group. Differences in intraprocedural end-point
      maintenance between the 2 groups were not statistically significant. CONCLUSIONS:
      Common intraprocedural end points such as voltage abatement, PV disconnection,
      and exit block persist only in a limited number of patients, even when the
      outcome is favorable during follow-up. Further investigation will be required to
      determine whether such data will have implications for ablation strategies.

PMID- 18086928
TI  - New-onset heart failure due to heart muscle disease in childhood: a prospective
      study in the United kingdom and Ireland.
AB  - BACKGROUND: We undertook the first prospective, national, multicenter study to
      describe the incidence and outcome of heart muscle disease-induced heart failure
      in children. METHODS AND RESULTS: Data were collected on patients admitted to a
      hospital through 2003 with a first episode of heart failure in the absence of
      congenital heart disease. All 17 pediatric cardiac centers in the United Kingdom
      and Ireland participated. Follow-up data were obtained to a minimum of 1 year.
      The incidence was 0.87/100,000 population <16 years (n=104; 53 girls; 95%
      confidence interval 0.71 to 1.05 per 100,000). Median age at presentation was 1
      year, with 82% in New York Heart Association class III to IV. Causes of heart
      failure included dilated cardiomyopathy (50 idiopathic, 8 familial), probable
      myocarditis (23), occult arrhythmia (7), anthracycline toxicity (5), metabolic
      disease (4), left ventricular noncompaction (3), and other (4). Overall 1-year
      survival was 82%, and event (death or transplantation)-free survival was 66%.
      Regression analysis showed older age and reduced systolic function on admission
      echocardiogram increased the event risk. Only 8% of event-free survivors (n=69)
      remained in New York Heart Association class III to IV, but 35 required
      readmission during the study period, and all but 8 remained on medication.
      CONCLUSIONS: This first national prospective study of new-onset heart failure in
      children has shown an incidence of 0.87/100,000. Multivariable analysis of
      survival data indicates a better outcome for younger children and for those with
      better systolic function at presentation, but overall, one third of children die
      or require transplantation within 1 year of presentation.

PMID- 18086929
TI  - Initial aspirin dose and outcome among ST-elevation myocardial infarction
      patients treated with fibrinolytic therapy.
AB  - BACKGROUND: Although treatment with immediate aspirin reduces morbidity and
      mortality in ST-elevation myocardial infarction, the optimal dose is unclear. We
      therefore compared the acute mortality and bleeding risks associated with the
      initial use of 162 versus 325 mg aspirin in fibrinolytic-treated ST-elevation
      myocardial infarction patients. METHODS AND RESULTS: Using combined data from the
      Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded
      Coronary Arteries (GUSTO I) and Global Use of Strategies to Open Occluded
      Coronary Arteries (GUSTO III) trials (n=48 422 ST-elevation myocardial infarction
      patients), we compared the association between initial aspirin dose of 162 versus
      325 mg and 24-hour and 7-day mortality, as well as rates of in-hospital
      moderate/severe bleeding. Results were adjusted for previously identified
      mortality and bleeding risk factors. Overall, 24.4% of patients (n=11 828)
      received an initial aspirin dose of 325 mg, and 75.6% (n=36 594) received 162 mg.
      The 24-hour mortality rates were 2.9% versus 2.8% (P=0.894) for those receiving
      an initial aspirin dose of 325 versus 162 mg. Mortality rates at 7 and 30 days
      were 5.2% versus 4.9% (P=0.118) and 7.1% versus 6.5% (P=0.017) among patients
      receiving the 325 versus 162 mg aspirin. After adjustment, aspirin dose was not
      associated with 24-hour (odds ratio [OR], 1.01; 95% CI, 0.82 to 1.25), 7-day (OR,
      1.00; 95% CI, 0.87 to 1.17), or 30-day (OR, 0.99; 95% CI, 0.87 to 1.12) mortality
      rates. No significant difference was noted for myocardial infarction or the
      composite of death or myocardial infarction between groups. In-hospital
      moderate/severe bleeding occurred in 9.3% of those treated with 325 mg versus
      12.2% among those receiving 162 mg (P<0.001). After adjustment, 325 mg was
      associated with a significant increase in moderate/severe bleeding (OR, 1.14; 95%
      CI, 1.05 to 1.24; P=0.003). CONCLUSIONS: These data suggest that an initial dose
      of 162 mg aspirin may be as effective as and perhaps safer than 325 mg for the
      acute treatment of ST-elevation myocardial infarction.

PMID- 18086930
TI  - Lack of association between the MEF2A gene and myocardial infarction.
AB  - BACKGROUND: Coronary artery disease (CAD) and myocardial infarction (MI) are
      caused in part by genetic factors. Recently, the MEF2A gene was linked to MI/CAD
      in a single pedigree with autosomal-dominant pattern of inheritance. In addition,
      genetic variants within the gene have been associated with MI in case-control
      settings, producing inconsistent results. METHODS AND RESULTS: The MEF2A gene was
      sequenced in MI patients from 23 MI families (> or =5 affected members per
      family), but no mutation was identified in any of these extended families.
      Moreover, the Pro279Leu variant in exon 7 was analyzed in 1181 unrelated MI
      patients with a positive family history for MI/CAD, in 533 patients with sporadic
      MI, and in 2 control populations (n=1021 and n=1055), showing no evidence for
      association with MI/CAD. In addition, a (CAG)n repeat in exon 11 was genotyped in
      543 sporadic MI patients and in 1190 controls without evidence for association
      with MI. Finally, analyzing 11 single-nucleotide polymorphisms from the GeneChip
      Mapping 500K Array, genotyped in 1644 controls and 753 cases, failed to provide
      evidence for association (region-wide P=0.23). CONCLUSIONS: Studying independent
      samples of >1700 MI patients, 2 large control populations, and multiple families
      with apparently mendelian inheritance of the disease, we found no evidence for
      any linkage or association signal in the MEF2A gene.

PMID- 18086931
TI  - Extreme lipoprotein(a) levels and risk of myocardial infarction in the general
      population: the Copenhagen City Heart Study.
AB  - BACKGROUND: Elevated lipoprotein(a) levels are associated with myocardial
      infarction (MI) in some but not all studies. Limitations of previous studies
      include lack of risk estimates for extreme lipoprotein(a) levels, measurements in
      long-term frozen samples, no correction for regression dilution bias, and lack of
      absolute risk estimates in the general population. We tested the hypothesis that
      extreme lipoprotein(a) levels predict MI in the general population, measuring
      levels shortly after sampling, correcting for regression dilution bias, and
      calculating hazard ratios and absolute risk estimates. METHODS AND RESULTS: We
      examined 9330 men and women from the general population in the Copenhagen City
      Heart Study. During 10 years of follow-up, 498 participants developed MI. In
      women, multifactorially adjusted hazard ratios for MI for elevated lipoprotein(a)
      levels were 1.1 (95% CI, 0.6 to 1.9) for 5 to 29 mg/dL (22nd to 66th percentile),
      1.7 (1.0 to 3.1) for 30 to 84 mg/dL (67th to 89th percentile), 2.6 (1.2 to 5.9)
      for 85 to 119 mg/dL (90th to 95th percentile), and 3.6 (1.7 to 7.7) for > or =120
      mg/dL (>95th percentile) versus levels <5 mg/dL (<22nd percentile). Equivalent
      values in men were 1.5 (0.9 to 2.3), 1.6 (1.0 to 2.6), 2.6 (1.2 to 5.5), and 3.7
      (1.7 to 8.0). Absolute 10-year risks of MI were 10% and 20% in smoking,
      hypertensive women aged >60 years with lipoprotein(a) levels of <5 and > or =120
      mg/dL, respectively. Equivalent values in men were 19% and 35%. CONCLUSIONS: We
      observed a stepwise increase in risk of MI with increasing levels of
      lipoprotein(a), with no evidence of a threshold effect. Extreme lipoprotein(a)
      levels predict a 3- to 4-fold increase in risk of MI in the general population
      and absolute 10-year risks of 20% and 35% in high-risk women and men.

PMID- 18086932
TI  - Platelet-derived stromal cell-derived factor-1 regulates adhesion and promotes
      differentiation of human CD34+ cells to endothelial progenitor cells.
AB  - BACKGROUND: Peripheral homing of progenitor cells in areas of diseased organs is
      critical for tissue regeneration. The chemokine stromal cell-derived factor-1
      (SDF-1) regulates homing of CD34+ stem cells. We evaluated the role of platelet
      derived SDF-1 in adhesion and differentiation of human CD34+ cells into
      endothelial progenitor cells. METHODS AND RESULTS: Adherent platelets express
      substantial amounts of SDF-1 and recruit CD34+ cells in vitro and in vivo. A
      monoclonal antibody to SDF-1 or to its counterreceptor, CXCR4, inhibits stem cell
      adhesion on adherent platelets under high arterial shear in vitro and after
      carotid ligation in mice, as determined by intravital fluorescence microscopy.
      Platelets that adhere to human arterial endothelial cells enhance the adhesion of
      CD34+ cells on endothelium under flow conditions, a process that is inhibited by
      anti-SDF-1. During intestinal ischemia/reperfusion in mice, anti-SDF-1 and anti
      CXCR4, but not isotype control antibodies, abolish the recruitment of CD34+ cells
      in microcirculation. Moreover, platelet-derived SDF-1 binding to CXCR4 receptor
      promotes platelet-induced differentiation of CD34+ cells into endothelial
      progenitor cells, as verified by colony-forming assays in vitro. CONCLUSIONS:
      These findings imply that platelet-derived SDF-1 regulates adhesion of stem cells
      in vitro and in vivo and promotes differentiation of CD34+ cells to endothelial
      progenitor cells. Because tissue regeneration depends on recruitment of
      progenitor cells to peripheral vasculature and their subsequent differentiation,
      platelet-derived SDF-1 may contribute to vascular and myocardial regeneration.

PMID- 18086933
TI  - Pioneers in cardiology: Frank Pantridge,CBE, MC, MD, FRCP, FACC.

PMID- 18086934
TI  - Cardiology patient page. New concepts of cardiopulmonary resuscitation for the
      lay public: continuous-chest-compression CPR.

PMID- 18086935
TI  - Images in cardiovascular medicine. Right atrial mass in a patient with T-cell
      chronic lymphocytic leukemia: an unusual mechanism of thrombus formation.

PMID- 18086936
TI  - Letter by Poullis and Warwick regarding article, "Paradoxical low-flow, low
      gradient severe aortic stenosis despite preserved ejection fraction is associated
      with higher afterload and reduced survival".

PMID- 18086937
TI  - Letter by Kriatselis and Roser regarding article, "Small or large isolation areas
      around the pulmonary veins for the treatment of atrial fibrillation? Results from
      a prospective randomized study".

PMID- 18086938
TI  - Continuous-chest-compression cardiopulmonary resuscitation for cardiac arrest.

PMID- 18086939
TI  - Cardiac report cards: how can they be made better?

PMID- 18086940
TI  - Is microvolt T-wave alternans the answer to risk stratification in heart failure?

PMID- 18086941
TI  - Pulmonary diseases and the heart.
AB  - The complex nature of interactions between the pulmonary and cardiovascular
      systems is becoming increasingly appreciated. Pulmonary vascular abnormalities
      are frequently present in patients with respiratory disorders, including chronic
      obstructive pulmonary disease, idiopathic pulmonary fibrosis, sarcoidosis,
      neuromuscular or chest wall disorders, and disorders of ventilatory control
      including sleep apnea syndromes and obesity hypoventilation syndrome. Pulmonary
      hypertension, classified as group III in the World Health Organization
      classification scheme for pulmonary hypertension, may result in severe right
      ventricular dysfunction caused by lung disease, also known as cor pulmonale. The
      development of cor pulmonale is generally associated with poorer prognosis and
      increased death. Systemic manifestations of lung disease, particularly
      obstructive disorders, are also particularly relevant because they are associated
      with increased cardiac death and impaired health status. This article will
      discuss the most common pulmonary diseases and disorders of ventilatory control
      that cause pulmonary vascular abnormalities and cor pulmonale, with particular
      concentration on how treatment of these diseases may affect the heart. In
      addition, the complex nature of cardiac and lung disease will also be explored,
      particularly with respect to the relationship between chronic obstructive
      pulmonary disease, systemic inflammation, atherosclerosis, and cardiovascular
      death, which is currently a very active focus of research.

PMID- 18086943
TI  - Mineralocorticoid signaling in transition to heart failure with normal ejection
      fraction.
AB  - Heart failure with normal ejection fraction occurs in elderly patients with
      hypertensive heart disease. We hypothesized that, in such patients,
      mineralocorticoid receptor activation accelerates the types of ventricular and
      vascular remodeling and dysfunction believed important in the transition to heart
      failure. We tested this hypothesis by administering deoxycorticosterone acetate
      (DOCA) without salt loading or nephrectomy to elderly dogs with experimental
      hypertension. Elderly dogs were made hypertensive by renal wrapping. After 5
      weeks, dogs were randomly assigned to DOCA (1 mg/kg per day IM; old hypertensive
      [OH]+DOCA; n=11) or not (OH; n=11) for 3 weeks. At week 8, conscious
      echocardiography and hemodynamic assessment under anesthesia were performed. DOCA
      resulted in further increases in conscious blood pressure (P<0.05) without
      increases in cardiac output or diastolic volume. In the conscious state,
      effective arterial elastance (P<0.05) and systemic vascular resistance (P=0.06)
      were increased, and systemic arterial compliance (P<0.05) was decreased in
      OH+DOCA animals. After anesthesia, instrumentation, and autonomic blockade, blood
      pressure was lower, whereas left ventricular (LV) systolic elastance, LV
      diastolic stiffness, and ex vivo myofiber diastolic stiffness were increased in
      OH+DOCA animals. LV collagen was increased in OH+DOCA animals (P<0.05 for all),
      but LV mass, LV brain natriuretic peptide, and titin isoform profiles were not.
      Neither aortic stiffness nor aortic structure was altered in OH+DOCA animals.
      These findings suggest that age and hypertensive heart disease enhance
      sensitivity to exogenous mineralocorticoid administration and that
      mineralocorticoid receptor activation could contribute to the transition to heart
      failure in elderly persons by promoting increases in LV diastolic and systolic
      stiffness.

PMID- 18086944
TI  - Lactotripeptides show no effect on human blood pressure: results from a double
      blind randomized controlled trial.
AB  - Milk-derived peptides with ACE-inhibiting properties may have antihypertensive
      effects in humans. We conducted a randomized double-blind placebo-controlled
      trial to examine the blood pressure lowering potential of 2 ACE-inhibiting
      lactotripeptides, ie, Isoleucine-Proline-Proline and Valine-Proline-Proline. We
      included 135 Dutch subjects with elevated systolic blood pressure who were
      otherwise healthy and who received no current antihypertensive treatment. After a
      2-week run-in period on placebo, subjects randomly received a daily dose of 200
      mL dairy drink with 14 mg lactotripeptides obtained by concentrating fermented
      milk, enzymatic hydrolysis, or chemical synthesis, or placebo for 8 weeks,
      followed by a 2-week wash-out. The primary outcome was 8-week change in office
      systolic blood pressure. Secondary outcomes were change in diastolic blood
      pressure, home blood pressure, 24-hour ambulatory blood pressure, plasma ACE
      activity, and plasma angiotensin II. Blood pressure at baseline was on average
      142/84 mm Hg. Lactotripeptides did not significantly change systolic blood
      pressure (P=0.46) or diastolic blood pressure (P=0.31) compared with placebo. The
      mean difference (95%-CI) in systolic blood pressure response between treatment
      and placebo was 2.8 mm Hg (-2.6;8.2) for concentrated fermented milk
      lactotripeptides, -0.5 mm Hg (-6.0;5.0) for enzymatic lactotripeptides, and 1.6
      mm Hg (-3.9;6.9) for synthetic lactotripeptides. Treatment neither had a
      significant effect on secondary outcome measures. In conclusion, the present
      study does not support the hypothesis of a blood pressure lowering effect of the
      lactotripeptides Isoleucine-Proline-Proline and Valine-Proline-Proline.

PMID- 18086945
TI  - Suppression of cardiomyocyte hypertrophy by inhibition of the ubiquitin
      proteasome system.
AB  - Inhibitors of the proteasome interfere with transcriptional regulation of growth
      signaling pathways and block cell cycle progression of mitotic cells. As growth
      signaling pathways are highly conserved between mitotic and postmitotic cells, we
      hypothesized that proteasome inhibition might also be a valuable approach to
      interfere with hypertrophic growth of postmitotic cardiomyocytes. To test this
      hypothesis, we analyzed the effects of proteasome inhibition on hypertrophic
      growth of neonatal rat cardiomyocytes. Partial inhibition of the proteasome
      effectively suppressed cardiomyocyte hypertrophy as determined by reduced cell
      size, inhibition of hypertrophy-mediated induction of RNA and protein synthesis,
      reduced expression of several hypertrophic marker genes, and diminished
      transcriptional activation of the BNP promotor. Importantly, suppression of
      hypertrophic growth was independent of the hypertrophic agonist used.
      Expressional profiling and subsequent Western blot and kinase assays revealed
      that proteasome inhibition induced a cellular stress response with reduced
      expression of conserved growth signaling mediators and impaired G1/S phase
      transition of cardiomyocytes. In hypertensive Dahl-salt sensitive rats,
      inhibition of the proteasome with low doses of the FDA approved proteasome
      inhibitor Velcade significantly reduced hypertrophic heart growth. Our data
      provide important insight into the suppressive effects of proteasome inhibitors
      on hypertrophic growth of cardiomyocytes and establish low-dose proteasome
      inhibition as a new and broad-spectrum approach to interfere with cardiac
      hypertrophy.

PMID- 18086946
TI  - Role of bradykinin, nitric oxide, and angiotensin II type 2 receptor in imidapril
      induced angiogenesis.
AB  - The angiotensin II (Ang II)-Ang II type 1 receptor pathway is proangiogenic,
      whereas studies showed that some angiotensin-converting enzyme inhibitors also
      stimulate angiogenesis in the setting of tissue ischemia, leaving a controversy
      of Ang II-mediated angiogenesis. We investigated whether an angiotensin
      converting enzyme inhibitor imidapril-induced angiogenesis might be mediated via
      the tissue bradykinin pathway. To rule out the conventional effects of Ang II on
      angiogenesis, we used Ang II type 1a receptor knockout (AT1aKO) mice. We examined
      the effects of the angiotensin-converting enzyme inhibitor imidapril on
      angiogenesis in a hindlimb ischemia model using AT1aKO mice. After induction of
      hindlimb ischemia, AT1aKO mice were treated with or without imidapril (1.0 or 0.1
      mg/kg per day for 21 days). Angiogenesis was quantified by laser Doppler blood
      flowmetry and capillary density. Angiogenesis was reduced in AT1aKO mice compared
      with wild-type mice. Imidapril with either low or high doses enhanced
      angiogenesis in AT1aKO mice (P<0.01). Ang II type 2 receptor antagonist
      (PD123319; 30 mg/kg per day) and B1 receptor antagonist (DesArg9-[Leu8]
      bradykinin; 50 nmol/kg per day) suppressed the imidapril-induced angiogenesis in
      AT1aKO mice to an extent even lower than that of nontreated AT1aKO mice. B2
      receptor antagonist (Hoechst 140; 100 microg/kg/d) and NO synthase inhibitor
      (N(G)-nitro-L-arginine methyl ester; 20 mg/kg per day) moderately attenuated the
      imidapril-mediated angiogenesis. RT-PCR revealed that vascular endothelial growth
      factor receptor 2 mRNA was reduced with PD123319, DesArg9-[Leu8]-bradykinin, or
      Hoechst 140, and vascular endothelial growth factor mRNA abundance was suppressed
      with PD123319 or DesArg9-[Leu8]-bradykinin. In conclusion, imidapril elicited
      angiogenesis in the setting of tissue ischemia in AT1aKO mice. This angiogenic
      effect might involve the Ang II-Ang II type 2 receptor pathway in addition to the
      bradykinin-B1 and bradykinin-B2 receptor/NO-dependent pathways.

PMID- 18086947
TI  - Should we target the sympathetic nervous system in the treatment of obesity
      associated hypertension?

PMID- 18086948
TI  - Apocynin, NADPH oxidase, and vascular cells: a complex matter.

PMID- 18086949
TI  - Altered soluble epoxide hydrolase gene expression and function and vascular
      disease risk in the stroke-prone spontaneously hypertensive rat.
AB  - Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids and
      represents a novel therapeutic target in cardiovascular disease treatment. We
      investigated the relationship among sequence variation in the sEH gene (Ephx2),
      sEH function, and risk of end-organ injury in strains of spontaneously
      hypertensive rat (SHRs) differing in their susceptibility to develop brain
      vascular disease. Brain Ephx2 expression was significantly lower in stroke-prone
      (SHR/A3) than in stroke-resistant (SHR/N) SHRs (5-fold; P<0.0001). Resequencing
      of the Ephx2 promoter in the 2 strains identified 3 polymorphisms that
      significantly influenced promoter transcriptional activity in vitro. Measurements
      of brain sEH enzyme activity and plasma levels of arachidonate and linoleate
      metabolites of sEH further suggested significant differences between the 2
      strains. Ratios of epoxyoctadecenoic acids to dihydroxyoctadecenoic acids were
      significantly higher, indicating a lower sEH activity in SHR/A3 than in SHR/N
      (P<0.0001). Plasma dihydroxyeicosatrienoic acid levels were lower in SHR/A3 than
      in SHR/N (P<0.0001), but plasma epoxyeicosatrienoic acids levels were similar in
      the 2 strains. Association analysis of Ephx2 polymorphism in the F2 progeny of an
      SHR/A3xSHR/N cross showed that animals carrying the SHR/A3 allele of Ephx2 had a
      greater risk of stroke and associated urinary proteinuria than animals that do
      not. Investigation of patterns of allelic similarities and differences among
      multiple stroke-prone and stroke-resistant SHR substrains showed that Ephx2
      belongs to a haplotype block shared among all of the stroke-prone but no stroke
      resistant substrains. These data support a role for Ephx2 polymorphism on sEH
      gene expression and function and risk of end-organ injury in the stroke-prone
      SHR.

PMID- 18086950
TI  - Inversion region for hypertension and brachydactyly on chromosome 12p features
      multiple splicing and noncoding RNA.
AB  - Autosomal-dominant hypertension and brachydactyly (Online Mendelian Inheritance
      in Man 112410) is a prototype-translational research project. We used interphase
      fluorescent in situ hybridization and discovered complex rearrangements on
      chromosome 12p in 5 families but elucidated a common inverted region in the
      linkage interval. The inversion contains no known gene. However, we found 5
      expressed sequence tags in databases. We used 5'- and 3'-Rapid Amplification of
      cDNA Ends PCR for elongation of the transcripts in phenotype-relevant tissue
      (fetal aorta, fetal brain, and fetal cartilage). We detected tissue-specific
      multiple splicing with different exon usage of 32 exons in the gene-related
      structure. These different transcripts lack both open reading frames and Kozak
      sequences. In vitro transcription/translation experiments did not identify any
      peptide-related molecules. We then performed quantitative RT-PCR to test for
      differential expression of the various spliced transcripts in the total
      fibroblast RNA of affected and nonaffected Turkish family members. Skin
      fibroblasts of affected individuals have a significantly increased proliferation
      rate compared with nonaffected individuals. Ten of 12 spliced exon combinations
      representing all of the spliced variants do not show a significantly different
      RNA expression rate. However, 2 RT-PCR products are exclusively expressed in
      nonaffected individuals. Both reverse transcription amplicons share 1 exon. This
      result is surprising because of the autosomal-dominant mode of inheritance of the
      trait. RNA secondary prediction of this single exon results in a stable stem-loop
      structure known to be essential for microRNA processing. We are pursuing the
      possibility of microRNA expression in affected patients that leads to complete
      down regulation of a spliced transcript.

PMID- 18086951
TI  - Effects of angiotensin type 2 receptor overexpression in the rostral
      ventrolateral medulla on blood pressure and urine excretion in normal rats.
AB  - Central angiotensin II plays a critical role in the regulation of cardiovascular
      function and autonomic activity, in part, via angiotensin type 1 receptors in the
      rostral ventrolateral medulla (RVLM). Increasing evidence indicates that
      angiotensin II can also act on angiotensin type 2 receptors (AT(2)Rs) to exert
      antagonistic effects. In the current study we determined the effects of
      overexpression of AT(2)R in the RVLM on sodium and water excretion and on blood
      pressure in conscious rats. The overexpression of AT(2)R was induced by bilateral
      microinjection of the AT(2)R adenovirus (Ad5-SYN-AT2R-IRES-EGFP, 2.5 x 10(6)
      infection units in 0.5 microL; Ad5-SYN-EGFP as the control, 2.5 x 10(6) infection
      units in 0.5 microL) into the RVLM of rats. Immunofluorescence staining showed
      that microinjection of AT(2)R adenovirus into the RVLM evoked local
      overexpression. Significant overexpression of AT(2)R in the RVLM began at 24
      hours and was sustained up to 12 days after microinjection. Overexpression of
      AT(2)R in the RVLM significantly decreased the nocturnal arterial blood pressure
      and increased the 24-hour urine excretion at days 2, 3, and 4 after gene delivery
      compared with the control rats. These alterations were abolished by the
      microinfusion of captopril into the RVLM and were enhanced by angiotensin II
      infusion. Overexpression of AT(2)R in the RVLM also significantly decreased the
      urine concentration of noradrenaline and 24-hour noradrenaline excretion (1.1+/
      0.5 microg in control rats and 2.4+/-0.5 microg in AT(2)R rats; P<0.05). These
      results suggest that overexpression of AT(2)R in the RVLM induced a diuresis that
      may be mediated, in part, by sympathoinhibition.

PMID- 18086952
TI  - Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity,
      hypertension, and insulin resistance: a novel murine model of developmental
      programming.
AB  - Maternal obesity is increasingly prevalent and may affect the long-term health of
      the child. We investigated the effects of maternal diet-induced obesity in mice
      on offspring metabolic and cardiovascular function. Female C57BL/6J mice were fed
      either a standard chow (3% fat, 7% sugar) or a palatable obesogenic diet (16%
      fat, 33% sugar) for 6 weeks before mating and throughout pregnancy and lactation.
      Offspring of control (OC) and obese dams (OO) were weaned onto standard chow and
      studied at 3 and 6 months of age. OO were hyperphagic from 4 to 6 weeks of age
      compared with OC and at 3 months locomotor activity was reduced and adiposity
      increased (abdominal fat pad mass; P<0.01). OO were heavier than OC at 6 months
      (body weight, P<0.05). OO abdominal obesity was associated with adipocyte
      hypertrophy and altered mRNA expression of beta-adrenoceptor 2 and 3, 11 beta HSD
      1, and PPAR-gamma 2. OO showed resistance artery endothelial dysfunction at 3
      months, and were hypertensive, as assessed by radiotelemetry (nighttime systolic
      blood pressure at 6 months [mm Hg] mean+/-SEM, male OO, 134+/-1 versus OC, 124+/
      2, n=8, P<0.05; female OO, 137+/-2 versus OC, 122+/-4, n=8, P<0.01). OO skeletal
      muscle mass (tibialis anterior) was significantly reduced (P<0.01) OO fasting
      insulin was raised at 3 months and by 6 months fasting plasma glucose was
      elevated. Exposure to the influences of maternal obesity in the developing mouse
      led to adult offspring adiposity and cardiovascular and metabolic dysfunction.
      Developmentally programmed hyperphagia, physical inactivity, and altered
      adipocyte metabolism may play a mechanistic role.

PMID- 18086953
TI  - Urotensin II and cardiomyopathy in end-stage renal disease.
AB  - Circulating urotensin (UTN) is increased in patients with heart failure and in
      patients with renal diseases, and UTN antagonism is currently considered as a
      potential treatment for these conditions. Contrary to this contention, studies in
      end-stage renal disease suggest that, perhaps because of interference with
      sympathetic and NO systems, UTN may be cardioprotective. Therefore, we
      investigated the relationship between circulating UTN and echocardiographic
      parameters of left ventricular function (midwall fractional shortening), left
      atrial volume, and myocardial geometry (mean wall thickness and relative wall
      thickness) in 191 patients with end-stage renal disease. UTN was associated
      directly (r=0.39; P<0.001) with left ventricular systolic function and inversely
      with left atrial volume (r=-0.40; P<0.001) and the muscular component of the left
      ventricular (UTN versus mean wall thickness: r=-0.30, P<0.001; UTN versus
      relative wall thickness: r=-0.32, P<0.001). Adjustment for a series of 11 risk
      factors produced a relatively small change in the strength of these
      relationships. However, further adjustment for plasma norepinephrine or,
      particularly so, for the endogenous inhibitor of NO synthase asymmetrical
      dimethyl arginine produced a 33% to 50% decrease in the strength of such
      associations. Of note, there was a strong UTN-asymmetrical dimethyl arginine
      interaction in determining midwall fractional shortening (P=0.001) and mean wall
      thickness (P=0.006). These data support the hypothesis that high UTN is
      cardioprotective in end-stage renal disease and that interference by UTN with
      sympathetic activity and NO synthesis represents an intermediate mechanism
      mediating the favorable echocardiographic profile of patients with high UTN.
      Additional mechanistic insights may be needed before launching long-term clinical
      trials with UTN antagonists in patients with end-stage renal disease.

PMID- 18086954
TI  - Importance of measuring the time course of flow-mediated dilatation in humans.
AB  - Flow-mediated dilatation (FMD) is widely used to describe conduit artery
      endothelial function. The traditional approaches to FMD calculation assess
      diameter change at arbitrary time points after occluding cuff deflation. The aim
      of this study was to examine the time course of brachial artery FMD after a 5
      minute period of forearm ischemia in 12 young, 12 fitness matched older and 12
      older untrained subjects. Edge-detection and wall tracking of high resolution B
      mode arterial ultrasound images, combined with synchronized Doppler waveform
      envelope analysis, were used to calculate brachial artery diameter, blood flow,
      and shear rate continuously across the cardiac cycle after forearm ischemia. FMD
      was significantly higher in young healthy subjects (7.8+/-3.2%) compared with
      sedentary older subjects (5.2+/-2.8%, P<0.05) but not trained older subjects
      (6.4+/-2.3%). Time to peak diameter differed between young (50+/-11 seconds) and
      both older groups (trained; 80+/-21, P<0.001; sedentary: 83+/-36 seconds,
      P<0.001). A large proportion (>42%) of true peak diameters fell outside the time
      frames typically used to assess FMD in the literature. When calculated according
      to the commonly used approach, ie, 60 s after cuff deflation, FMD was
      significantly lower compared with true peak FMD in all groups (P<0.001), and no
      differences were evident between the groups. The time course of FMD differs
      significantly between young and older subjects. Studies assuming that peak
      dilation occurs at an arbitrary time point, or within limited time windows, may
      draw misleading conclusions regarding differences between groups. More
      sophisticated approaches to measurement of FMD are required if it is to be
      considered a valid biomarker of vascular disease.

PMID- 18086955
TI  - Relation of dietary salt and aldosterone to urinary protein excretion in subjects
      with resistant hypertension.
AB  - Experimental data indicate that the cardiorenal effects of aldosterone excess are
      dependent on concomitant high dietary salt intake. Such an interaction of
      endogenous aldosterone and dietary salt has not been observed previously in
      humans. We assessed the hypothesis that excess aldosterone and high dietary
      sodium intake combine to worsen proteinuria in patients with resistant
      hypertension. Consecutive subjects with resistant hypertension (n=84) were
      prospectively evaluated by measurement of 24-hour urinary aldosterone (Ualdo),
      sodium, and protein (Uprot) excretion. Subjects were analyzed according to
      aldosterone status (high: Ualdo >or=12 microg/24 hours; or normal: <12 microg/24
      hours) and dietary salt intake based on tertiles of urinary sodium. The mean
      clinic blood pressure for all of the subjects was 161.4+/-22.4/89.8+/-13.5 mm Hg
      on an average of 4.3 medications. There was no blood pressure difference between
      study groups. Uprot was significantly higher in the 38 subjects with high Ualdo
      compared with the 46 subjects with normal Ualdo (143.0+/-83.8 versus 95.9+/-81.7
      mg/24 hours; P=0.01). Among subjects with high Ualdo, Uprot increased
      progressively across urinary sodium groups (P<0.05). In contrast, there was no
      difference in Uprot across sodium tertiles among subjects with normal Ualdo. A
      positive correlation between Uprot and urinary sodium (r=0.47; P=0.003) was
      observed in subjects with high Ualdo but not in subjects with normal Ualdo
      (r=0.18; P value not significant). These results suggest that aldosterone excess
      and high dietary salt combine to increase urinary protein excretion.

PMID- 18086956
TI  - Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant.
AB  - A large body of literature suggest that vascular reduced nicotinamide-adenine
      dinucleotide phosphate (NADPH) oxidases are important sources of reactive oxygen
      species. Many studies, however, relied on data obtained with the inhibitor
      apocynin (4'-hydroxy-3'methoxyacetophenone). Because the mode of action of
      apocynin, however, is elusive, we determined its mechanism of inhibition on
      vascular NADPH oxidases. In HEK293 cells overexpressing NADPH oxidase isoforms
      (Nox1, Nox2, or Nox4), apocynin failed to inhibit superoxide anion generation
      detected by lucigenin chemiluminescence. In contrast, apocynin interfered with
      the detection of reactive oxygen species in assay systems selective for hydrogen
      peroxide or hydroxyl radicals. Importantly, apocynin interfered directly with the
      detection of peroxides but not superoxide, if generated by xanthine/xanthine
      oxidase or nonenzymatic systems. In leukocytes, apocynin is a prodrug that is
      activated by myeloperoxidase, a process that results in the formation of apocynin
      dimers. Endothelial cells and smooth muscle cells failed to form these dimers
      and, therefore, are not able to activate apocynin. Dimer formation was, however,
      observed in Nox-overexpressing HEK293 cells when myeloperoxidase was
      supplemented. As a consequence, apocynin should only inhibit NADPH oxidase in
      leukocytes, whereas in vascular cells, the compound could act as an antioxidant.
      Indeed, in vascular smooth muscle cells, the activation of the redox-sensitive
      kinases p38-mitogen-activate protein kinase, Akt, and extracellular signal
      regulated kinase 1/2 by hydrogen peroxide and by the intracellular radical
      generator menadione was prevented in the presence of apocynin. These observations
      indicate that apocynin predominantly acts as an antioxidant in endothelial cells
      and vascular smooth muscle cells and should not be used as an NADPH oxidase
      inhibitor in vascular systems.

PMID- 18086957
TI  - The interaction between coronary endothelial dysfunction, local oxidative stress,
      and endogenous nitric oxide in humans.
AB  - In vitro and animal studies suggest that oxidative stress is associated with
      endothelial dysfunction. We tested whether local oxidative stress and nitric
      oxide (NO) bioavailability in the coronary circulation is associated with
      coronary endothelial dysfunction in humans. Blood samples were obtained
      simultaneously from the left main coronary artery and the coronary sinus for
      measurement of F2-isoprostanes, myeloperoxidase, nitrotyrosine, and superoxide
      dismutase in 20 patients without significant coronary disease. Afterward,
      coronary blood flow and the vascular response to intracoronary acetylcholine and
      NG-monomethyl-L-arginine (L-NMMA) were assessed. The gradient of isoprostanes
      between the arterial levels and coronary sinus correlated with the change in
      coronary artery diameter in response to acetylcholine (r=-0.79, P<0.0001).
      Isoprostanes net production across the left anterior descending artery territory
      correlated with a decrease in superoxide dismutase activity (r=0.66, P=0.002) and
      decrease in coronary artery diameter in response to L-NMMA (rs=0.48, P<0.05).
      Myeloperoxidase and nitrotyrosine gradients were similar in patients with
      endothelial dysfunction and controls. The effect of L-NMMA was similar in both
      groups. We conclude that coronary endothelial dysfunction in humans is
      characterized by local enhancement of oxidative stress without a decrease in
      basal NO release. This study supports the hypothesis that local oxidative stress
      has a role in reduction of NO bioavailability in humans with coronary endothelial
      dysfunction.

PMID- 18086958
TI  - Improving the quality of head and neck cancer care.
AB  - The 2001 report by the Institute of Medicine (IOM) titled Crossing the Quality
      Chasm: A New Health System for the 21st Century highlighted the gap that exists
      between what we know to be effective, beneficial care and the care that is often
      delivered to an individual patient.(1) In the report, the IOM stated, "Between
      the health care we have and the care we could have lies not just a gap, but a
      chasm."(1)((p1)) The report, signifying a national initiative to improve the
      quality of care in the United States, articulated the following 6 aims for a new
      health care system: (1) to increase the safety of health care by avoiding
      injuries to patients through care intended to help them; (2) to provide effective
      services based on scientific knowledge and to avoid services of no proven
      benefit; (3) to deliver individualized treatment respectful of and responsive to
      the patient's preferences, needs, and values; (4) to deliver timely care by
      reducing wait times and harmful delays; (5) to increase efficiency by not wasting
      equipment, supplies, ideas, and energy; and (6) to deliver care that is equitable
      and does not vary by personal characteristics, patient sex, ethnicity, geography,
      and social economic status. The IOM also recognized a need to optimize quality
      cancer care in the United States.

PMID- 18086959
TI  - Endoscopic carbon dioxide laser surgery for glottic cancer recurrence after
      radiotherapy: oncological results.
AB  - OBJECTIVE: To evaluate local control, organ preservation, and complications after
      endoscopic laser surgery for early recurrent glottic cancer after radiotherapy.
      DESIGN: Retrospective study. SETTING: European Institute of Oncology, Milan,
      Italy. PATIENTS: The study, which was conducted between May 1999 and September
      2005, included 37 consecutive patients (33 men and 4 women) with recurrent
      glottic cancer after radiotherapy. Selection criteria were as follows: rcTis,
      rcT1, or rcT2 with subglottic or supraglottic involvement of less than 5 mm and
      no arytenoid invasion; adequate laryngeal exposure; no previous open surgery; no
      contraindications to general anesthesia; and signed consent. INTERVENTIONS:
      Endoscopic laser surgery with curative intent using types III to V cordectomies
      according to the European Laryngological Association. MAIN OUTCOME MEASURES: Five
      year actuarial recurrence-free and overall survival, complications, and rate of
      laryngeal preservation. RESULTS: The clinical classifications of the recurrences
      were rcTis (n = 4), rcT1a (n = 10), rcT1b (n = 11), and rcT2 (n = 12). The
      pathologic classifications of the recurrences were rpT0 (n = 2), rpTis (n = 5),
      rpT1a (n = 9), rpT1b (n = 3), rpT2 (n = 14), and rpT3 (n = 4). The median follow
      up was 44 months (range, 18-88 months). New recurrences developed in 13 patients
      (35%): 11 were treated by total laryngectomy, 1 by supracricoid laryngectomy, and
      1 by chemotherapy. Three patients died of laryngeal cancer, 1 is alive with
      disease, and 1 died of a second cancer. Five-year actuarial recurrence-free and
      overall survival rates were 58% and 86%, respectively. The larynx was preserved
      in 26 patients (70%). Laryngeal stenosis was the most common major complication
      (in 3 of 4 women and 1 of 33 men). CONCLUSIONS: Endoscopic laser surgery is a
      safe and effective salvage procedure in selected cases involving glottic
      recurrence after radiotherapy. Oncological results are satisfactory, and organ
      preservation can be achieved in a high proportion of cases; however, the risk of
      laryngeal stenosis is high in women.

PMID- 18086961
TI  - Robotic endoscopic surgery of the skull base: a novel surgical approach.
AB  - OBJECTIVE: To describe a novel robotic surgical approach that allows adequate
      endoscopic access for resection of tumors involving the anterior and central
      skull base and allows 2-handed, tremor-free, endoscopic dissection and precise
      suturing of dural defects. DESIGN: Transnasal endoscopic approaches are being
      increasingly used for surgical access and resection of tumors of the anterior and
      central skull base. One major disadvantage of this approach is the inability to
      provide watertight dural closure and reconstruction, which limits its safety and
      widespread adoption in surgery of intracranial skull base tumors. Other
      disadvantages include limited depth perception and several ergonomic constraints.
      Four human cadaver specimens were used for this study. The surgical approach
      starts with bilateral sublabial incisions and wide anterior maxillary
      antrostomies (Caldwell-Luc). Transantral access to the nasal cavity is gained
      through bilateral wide middle meatal antrostomies. A posterior nasal septectomy
      facilitates bilateral access by joining both nasal cavities into 1 surgical
      field. The da Vinci Surgical System is then "docked" by introducing the camera
      arm port through the nostril and the right and left surgical arm ports through
      the respective anterior and middle antrostomies, into the nasal cavity. A 5-mm
      dual-channel endoscope coupled with a dual charge-coupled device camera is
      inserted in the camera port and allows for 3-dimensional visualization of the
      surgical field at the surgeon's console. Using the robotic surgical arms, the
      surgeon may perform endoscopic anterior or posterior ethmoidectomy,
      sphenoidotomy, or resection of the middle or superior turbinates depending on the
      extent of needed surgical exposure. In addition, resection of the cribriform
      plate is performed robotically with sharp dissection of the skull base. The dural
      defect is then repaired with a 6-0 nylon suture. RESULTS: Adequate access to the
      anterior and central skull base, including the cribriform plate, fovea
      ethmoidalis, medial orbits, planum sphenoidale, sella turcica, suprasellar and
      parasellar regions, nasopharynx, pterygopalatine fossa, and clivus, was obtained
      in all cadaveric dissections. The 3-dimensional visualization obtained by the
      dual-channel endoscope at the surgeon's console provided excellent depth
      perception. The most significant advantage was the ability of the surgeon to
      perform 2-handed tremor-free endoscopic closure of dural defects. CONCLUSIONS:
      Transantral robotic surgery provides adequate endoscopic access to the anterior
      and central skull base. To our knowledge, this is the first study to report the
      feasibility and advantages of robotic-assisted endoscopic surgery of the skull
      base. This novel approach also allows for 3-dimensional, 2-handed, tremor-free
      endoscopic dissection and precise closure of dural defects. These advantages may
      expand the indications of minimally invasive endoscopic approaches to the skull
      base.

PMID- 18086960
TI  - Transoral laser microsurgery for advanced laryngeal cancer.
AB  - OBJECTIVE: To report the oncologic and functional outcomes of transoral laser
      microsurgery (TLM) in the treatment of advanced laryngeal cancer. DESIGN:
      Prospective case series study. SETTING: Multi-institution (academic, tertiary
      referral centers). PATIENTS: A total of 117 patients with pathologically
      confirmed T2 to T4 lesions, stage III or stage IV, glottic or supraglottic
      carcinoma of the larynx were treated with TLM from 1997 to 2004. All patients had
      a minimum follow-up period of 2 years. INTERVENTIONS: Transoral laser
      microsurgery in 117 patients, neck dissection in 91 patients, and adjuvant
      radiotherapy in 45 patients. MAIN OUTCOME MEASURES: End points analyzed included
      laryngeal preservation, overall survival, disease-free survival, local control,
      locoregional control, and distant metastases. Postoperative complications,
      tracheotomy rate, and feeding-tube dependence were also examined. RESULTS: The
      median follow-up period among surviving patients was 5 years. At 2 years, the
      percentage of patients with an intact larynx after treatment was 92%. The 2-year
      local control and locoregional control rates were 82% and 77%, respectively. The
      2-year disease-free and overall survival rates were 68% and 75%, respectively.
      The 5-year Kaplan-Meier estimates were local control, 74%; locoregional, control,
      68%; disease-free survival, 58%; overall survival, 55%; and distant metastases,
      14%. Four patients (3%) experienced treatment-related deaths. Seven patients (6%)
      experienced a postoperative hemorrhage. Of those patients with organ preservation
      and no disease recurrence, 2 patients (3%) were tracheotomy dependent, and 4
      patients (7%) were feeding-tube dependent. CONCLUSIONS: In patients with advanced
      laryngeal cancer, TLM with or without radiotherapy is a valid treatment strategy
      for organ preservation. Furthermore, low morbidity and mortality and excellent
      oncologic and functional outcomes make TLM an attractive therapeutic option.

PMID- 18086962
TI  - Robotic skull base surgery: preclinical investigations to human clinical
      application.
AB  - OBJECTIVE: To develop a minimally invasive surgical technique for the treatment
      of parapharyngeal space and infratemporal fossa skull base neoplasms using the
      technical and optical advantages of robotic surgical instrumentation. DESIGN: A
      robotics skull base surgery program at the University of Pennsylvania,
      Philadelphia, was initiated in the fall of 2005. Six experimental procedures
      focusing on developing approaches to the parapharyngeal space and infratemporal
      fossa were performed on a total of 2 cadavers and 1 mongrel dog. Based on the
      preclinical work, transoral robotic surgery (TORS) was then performed in February
      2007 on 1 human patient with a parapharyngeal to infratemporal fossa cystic
      neoplasm as part of a large prospective human trial. SETTING: In each cadaver and
      in the dog, a TORS approach to parapharyngeal space and infratemporal fossa was
      performed bilaterally and in an approved training facility using the da Vinci
      Surgical System. For the human surgical case, a TORS approach was evaluated on
      one side for a benign neoplasm. The human patient underwent TORS of the
      parapharyngeal space and infratemporal fossa under an institutional review board
      approved prospective clinical trial. PATIENTS: For the human clinical trial, a
      TORS approach was evaluated for a patient with a benign neoplasm of the
      parapharyngeal space and infratemporal fossa. MAIN OUTCOME MEASURES: The ability
      to access and dissect tissues within the various areas of the parapharynx and
      infratemporal fossa was evaluated, and techniques to enhance visualization and
      instrumentation were developed. RESULTS: Using TORS approaches permitted
      excellent access, visualization, and tissue dissection within the parapharyngeal
      space and infratemporal fossa in both the cadaver and canine experiments. In the
      first known human surgical case, TORS was used to remove a parapharyngeal space
      and infratemporal fossa cystic neoplasm. Wide visualization, followed by complete
      resection using the identical techniques developed in the preclinical models, was
      achieved. The robotic procedure allowed adequate and safe identification of the
      internal carotid artery and cranial nerves, and excellent hemostasis was achieved
      with no complications during or after surgery. CONCLUSIONS: The TORS approaches
      provided excellent 3-dimensional visualization and instrument access that allowed
      successful parapharyngeal space and infratemporal fossa surgical resections from
      cadaver models to the first known human patient application. Robotic surgery for
      the skull base holds potential as a minimally invasive approach to skull base
      neoplasms; however, continued development and investigation is warranted in a
      prospective human clinical trial before final conclusions can be drawn as to the
      full advantages and limitations of this approach.

PMID- 18086963
TI  - Transoral robotic surgery: radical tonsillectomy.
AB  - OBJECTIVE: To describe and show the feasibility of a new surgical technique for
      transoral robotic surgery (TORS) radical tonsillectomy. DESIGN: A prospective,
      phase 1 clinical trial. SETTING: Academic, tertiary referral center. PATIENTS: A
      total of 27 participants were prospectively selected using a volunteer sample.
      All eligible patients agreed to participate in the study. INTERVENTIONS: Patients
      underwent TORS radical tonsillectomy for previously untreated invasive squamous
      cell carcinoma of the tonsillar region without free-flap reconstruction, staged
      neck dissection, and adjuvant therapy. MAIN OUTCOME MEASURES: Outcome measures
      included final pathologic margin status, need for short- and long-term
      tracheotomy tube placement, and need for gastrostomy tube feedings among patients
      with a minimum 6-month follow-up. The incidence of significant postoperative
      complications was recorded. RESULTS: No mortality occurred. Final margins found
      to be negative for cancer were achieved in 25 of 27 patients (93%). Surgical
      complications included 1 case each of postoperative mucosal bleeding, delirium
      tremens, unplanned tracheotomy for temporary exacerbation of sleep apnea, and
      hypernasality and 2 cases of moderate trismus. Twenty-six of 27 patients (96%)
      were swallowing without the use of a gastrostomy. CONCLUSIONS: Radical
      tonsillectomy using TORS is a new technique that offers excellent access for
      resection of carcinomas of the tonsil with acceptable acute morbidity. Future
      reports will focus on long-term oncologic and functional outcomes.

PMID- 18086964
TI  - Minimal access parathyroidectomy using the focused lateral approach: technique,
      indication, and results.
AB  - OBJECTIVE: To describe the technique and results of minimal access
      parathyroidectomy using the focused lateral approach (FLA) under local anesthesia
      with intravenous sedation for excision of posteriorly located parathyroid glands.
      DESIGN: Review of medical records from a prospectively obtained database of
      patients. SETTING: Tertiary care university hospital. PATIENTS: The records of 88
      consecutive patients who underwent parathyroidectomy via FLA between November 13,
      2003, and January 26, 2007, were reviewed. MAIN OUTCOME MEASURES: The FLA was
      used when preoperative sestamibi single-photon emission computed tomography or
      ultrasonography showed an adenoma located superiorly, posteriorly, or
      retroesophageally. Intraoperative rapid parathyroid hormone assay was used to
      confirm a single adenoma in all cases. RESULTS: Eighty cases (91%) were
      successfully performed under intravenous sedation. In 4 patients, the procedure
      was converted from a lateral to an anterior approach. Seventy-one patients (81%)
      were discharged from the hospital the same day. The mean operative times for FLA
      were 82.6 minutes in the early part of the series and 62.9 minutes in 2006. There
      were no major complications. One patient experienced transient vocal cord
      paresis. One patient developed a pneumomediastinum, which resolved without
      intervention. Another patient developed a small hematoma, which required no
      treatment and resolved. CONCLUSIONS: The FLA is a safe and effective procedure
      for excision of parathyroid glands that are located superiorly, posteriorly, or
      retroesophageally. Its major advantage is the ability to remove glands located
      deep and posterior through a small incision under intravenous sedation. Although
      there is a learning curve, the overall operative times for minimally invasive
      parathyroidectomy decreased after experience was gained. The FLA improves the
      mean excision time for excision of posteriorly located parathyroid adenomas.

PMID- 18086965
TI  - Guidelines for radioguided parathyroid surgery.
AB  - OBJECTIVE: To confirm or refute the notion that only parathyroid adenomas have
      radioactivity higher than 20% of background. DESIGN: Retrospective analysis of a
      prospective patient data set. SETTING: Tertiary care referral center. PATIENTS:
      Forty-six patients (9 men and 37 women; mean +/- SD age, 53.7 +/- 12.1 years)
      underwent thyroid and parathyroid surgery between December 2005 and December 2006
      to collect data on ex vivo radioactivity percentages on a variety of tissues.
      INTERVENTIONS: Patients were injected with 296 to 925 MBq of technetium Tc 99m
      sestamibi 1(1/2) to 3(1/2) hours before surgery. Biopsy specimens were taken of
      normal parathyroid glands, normal thyroid tissue, and lymph nodes and ex vivo
      radioactivity was recorded. Hyperplastic parathyroid glands and adenomatous
      glands were excised. Finally, some enlarged glands were cut into segments, and
      radioactivity counts were recorded and compared with the weight of the tissue.
      MAIN OUTCOME MEASURES: All counts were compared with radioactivity percentages in
      the surrounding tissues, and results were expressed as a function of these
      background radioactive counts. RESULTS: The mean +/- SD ex vivo background
      radioactivity of parathyroid adenomas was 148.5% +/- 83.1% of background activity
      (range, 40.1%-388.9% but never less than 40%). The mean +/- SD ex vivo background
      radioactivity of hyperplastic parathyroid glands was 74.6% +/- 18.0% (range,
      49.5%-109.1% but never less than 40%). A significant difference was found in ex
      vivo background radioactivity between pathologic parathyroid tissue and the other
      tissue specimens studied (normal parathyroid glands [2.4% +/- 1.8%], thyroid
      tissue [4.5% +/- 2.8%], lymph nodes [1.6% +/- 0.8%], and fat [0.4% +/- 0.3%]).
      CONCLUSIONS: Ex vivo radioactivity percentages can differentiate hyperactive
      parathyroid tissue from any other tissue, but they cannot differentiate adenoma
      from hyperplasia and thus are not helpful in ruling out multiglandular disease.
      Interpretation of ex vivo radioactivity percentages should take into
      consideration the size of the specimen.

PMID- 18086966
TI  - The role of ultrasonography in parathyroid surgery.
AB  - OBJECTIVE: To assess the role of high-resolution ultrasonography in the
      preoperative evaluation of patients with hyperparathyroidism. DESIGN:
      Retrospective cohort. SETTING: Tertiary care university hospital. PATIENTS: Three
      hundred seventeen patients with hyperparathyroidism who underwent preoperative
      assessment with ultrasonography and/or sestamibi scan and surgical treatment
      between October 2003 and October 2006. MAIN OUTCOME MEASURES: Descriptive
      statistics of localization imaging studies and detection of concomitant thyroid
      disease in patients presenting with hyperparathyroidism. RESULTS: Ultrasonography
      correctly localized the parathyroid adenoma(s) in 148 (69.4%) of the 229 patients
      with these lesions. Sestamibi scans correctly localized the parathyroid
      adenoma(s) in 133 (58.1%) of the 229 patients. The agreement between the 2
      imaging procedures was moderate (kappa = 0.23; 95% confidence interval, 0.12
      0.36). Of 317 patients with hyperparathyroidism, 96 (30.3%) had clinically
      significant concomitant thyroid disease requiring partial or total thyroidectomy.
      Histopathologic examination revealed benign thyroid disease in 80 (83.0%) of the
      96 patients and thyroid carcinoma in 16 (16.6%). CONCLUSION: Ultrasonography is a
      useful tool in the preoperative evaluation of patients with hyperparathyroidism
      both for localization of parathyroid adenomas and for the diagnosis of
      concomitant thyroid disease.

PMID- 18086967
TI  - Cost-effective management of low-risk papillary thyroid carcinoma.
AB  - OBJECTIVE: To compare the 20-year cost-effectiveness of initial hemithyroidectomy
      vs total thyroidectomy in the management of small papillary thyroid cancer in the
      low-risk patient. DESIGN: Pooled data from the published literature were used to
      determine key statistics for decision analysis such as rates of recurrence, rates
      of complications for all interventions undertaken, and rates of death. The 2005
      costs were obtained from the US Department of Health and Human Services, as well
      as from Medicare reimbursement schedules. Future costs were discounted at 6%.
      SETTING: Decision analysis study. PATIENTS: Data from the published literature.
      MAIN OUTCOME MEASURES: A state-transition (Markov) decision model was constructed
      based on the most recent American Thyroid Association recommendations. A cost
      effectiveness analysis was performed using fixed probability estimates and Monte
      Carlo microsimulation, with effectiveness defined as cause-specific mortality or
      recurrence-free survival. After identifying initial results, sensitivity and
      threshold analyses were performed to assess the strength of the recommendations.
      RESULTS: Initial probability estimates were determined from a review of 940
      abstracts and 31 relevant studies examining outcomes in patients with low-risk
      thyroid cancer undergoing thyroidectomy or neck dissection. During 20 years, cost
      estimates (including initial surgery, follow-up, and treatment of recurrence)
      were between $13,896.81 and $14,241.24 for total thyroidectomy and between
      $15,037.58 and $15,063.75 for hemithyroidectomy. Cause-specific mortality was
      similar for both treatment strategies, but recurrence-free survival was higher in
      the total thyroidectomy group. Sensitivity and threshold analyses demonstrated
      that these results were sensitive to rates of recurrence and cost of follow-up
      but remained robust when compared with willingness to pay. CONCLUSIONS: Total
      thyroidectomy dominates over hemithyroidectomy as initial treatment for low-risk
      papillary thyroid cancer. However, in sensitivity analyses, these results varied
      by institution because of heterogeneity in long-term treatment outcomes. With
      changing protocols of management, it is possible that hemithyroidectomy will
      emerge as being more cost-effective. Long-term prospective trials are necessary
      to validate our findings.

PMID- 18086968
TI  - Laryngeal nerve monitoring and minimally invasive thyroid surgery: complementary
      technologies.
AB  - OBJECTIVE: To determine the feasibility of the combined use of laryngeal nerve
      monitoring and minimally invasive thyroid surgery. DESIGN: Prospective,
      nonrandomized analysis of single-surgeon experience. SETTING: Academic
      institution. PATIENTS: Consecutive series of patients undergoing both minimally
      invasive thyroid surgery and laryngeal nerve monitoring. MAIN OUTCOME MEASURES:
      Incision length and incidence of temporary or permanent laryngeal nerve injury.
      RESULTS: Two hundred eighty-three patients underwent thyroid surgery at the
      Medical College of Georgia, Augusta, between January 2004 and November 2006. Some
      type of minimal-access approach (endoscopic or nonendoscopic) was used in 137
      cases (48.4%) in which general anesthesia was administered. Laryngeal nerve
      monitoring was performed in 73 (53.3%) of these 137 cases, although the
      proportion of cases in which it was performed increased significantly from 8.7%
      (2 of 23 cases) in 2004 to 95.2% (58 of 61 cases) in 2006 (P < .001). There were
      no cases of permanent nerve injury. The incidence of temporary recurrent
      laryngeal nerve paresis was 4.3% (4 of 92 nerves at risk) in the cases in which
      laryngeal nerve monitoring was used and 6.0% (5 of 84 nerves at risk) in the
      cases in which the nerve was visually identified without use of a monitor. This
      difference failed to reach statistical significance (P = .73), which may reflect
      an insufficient sample size. CONCLUSION: Monitoring of the laryngeal nerves is
      feasible in minimal-access thyroid surgery and may serve as a meaningful adjunct
      to the visual identification of nerves.

PMID- 18086969
TI  - Impact of preoperative ultrasonographic staging of the neck in papillary thyroid
      carcinoma.
AB  - OBJECTIVE: To determine the frequency of occult macroscopic metastasis detected
      by preoperative US evaluation of the neck in patients with PTC. Papillary thyroid
      carcinoma (PTC) is a malignancy with a high rate of lymph node metastasis. The
      findings of routine thyroid ultrasonography (US) and physical examination may
      underestimate metastatic disease. Thus, we propose that patients diagnosed as
      having PTC undergo preoperative US staging of the neck. DESIGN: This prospective
      study included 60 patients diagnosed as having PTC from January 1 through June
      30, 2006. Patients had undergone previous thyroid US evaluation with no palpable
      adenopathy. Lymph nodes were deemed suspicious by US findings with a minor axis
      greater than 10 mm, a minor axis greater than 50% of the major axis, or
      hyperechogenicity with or without microcalcifications. Metastasis was confirmed
      by fine-needle aspiration biopsy or frozen section analysis. Patients with
      confirmed metastasis underwent a neck dissection. The location of adenopathy
      reported by US was correlated with the pathological report. RESULTS: The US
      evaluation identified 12 of 60 patients (20%) with adenopathy suggestive of
      metastasis. Metastasis was confirmed in 11 of 12 patients (92%). Metastasis was
      found in 1 of 48 patients who had a negative US finding. Overall, sensitivity,
      specificity, and positive and negative predictive values were 92%, 98%, 92%, and
      98%, respectively. All neck levels with suspicious adenopathy detected by US
      evaluation, with 1 exception, were confirmed by pathological findings. Nine
      patients had additional neck levels involved with microscopic disease undetected
      by the US evaluation. CONCLUSIONS: In patients with PTC, preoperative US
      evaluation of the neck is effective in detecting nonpalpable metastasis.
      Therefore, routine preoperative neck US evaluation is recommended to optimize
      primary surgical planning.

PMID- 18086970
TI  - The effect of altered Toll-like receptor 4 signaling on cancer cachexia.
AB  - OBJECTIVE: To determine whether mice unable to mount an intact inflammatory
      response because of a Toll-like receptor (TLR) pathway defect will develop less
      severe cancer cachexia. DESIGN: Prospective animal study. SETTING: Academic
      research center. SUBJECTS: Six- to eight-week-old, female C3H/HeJ mice (17-18 g)
      and age-, weight-, and sex-matched wild-type C3H/HeN mice, differing in that the
      HeJ mice have nonfunctional TLR4 due to a TLR4 double mutation (TLR4(d/d)).
      INTERVENTION: The mice were inoculated with equal numbers of SCCF-VII cells and
      housed in individual cages. MAIN OUTCOME MEASURES: Food intake, body weight,
      pretumor and posttumor body composition, circulating cytokines, and levels of a
      marker of muscle atrophy were analyzed. RESULTS: The wild-type HeN mice weighed
      less on average than the TLR4(d/d) mice (2.6 g vs 4.9 g) (P = .01). They consumed
      more food, had smaller tumors, and had less lean body mass and fat mass than the
      TLR4(d/d) mice. Interleukin 1beta level was significantly elevated in the tumor
      bearing HeN mice (mean gain of 259 pg/mL) but not in the TLR4(d/d) mice (P =
      .03). Both mouse strains had evidence of muscle atrophy. CONCLUSIONS: In spite of
      increased food intake and smaller tumors, the wild-type HeN mice had more severe
      cachexia than the TLR4(d/d) mice. The impaired ability to secrete proinflammatory
      cytokines such as interleukin 1beta may protect these animals from developing
      severe cancer cachexia. This animal model represents a novel system in which the
      host contributions to cachexia may be further studied.

PMID- 18086971
TI  - Factors predictive of survival in advanced laryngeal cancer.
AB  - OBJECTIVE: To determine the factors predictive of improved survival among
      patients with advanced laryngeal cancer. DESIGN: National hospital-based cancer
      registry. PATIENTS: Patients treated with total laryngectomy (TL), radiation
      therapy alone (RT), or combined chemotherapy and radiation therapy (chemo-RT).
      RESULTS: Of the 10,590 patients meeting the initial inclusion criteria, 7,019 had
      appropriate nonmissing values in all study variables and were included in the
      analysis. Overall, TL was significantly associated with increased likelihood of
      survival compared with RT or chemo-RT (P<.001). Among patients with stage III
      cancer, TL and chemo-RT had similar impacts on survival (each showed increased
      survival compared with RT), whereas TL was associated with significantly greater
      survival than chemo-RT or RT among patients with stage IV disease (P<.001).
      Overall survival was also decreased among men, black patients (compared with
      white patients), and patients with Medicare or Medicaid or those who were
      uninsured (compared with those with private insurance). CONCLUSIONS: Among
      patients with the most advanced disease (stage IV), TL was associated with
      increased survival compared with chemo-RT or RT, whereas both TL and chemo-RT
      improved survival over RT among patients with stage III cancer. Insurance type
      and black race also showed significant associations with survival, which may
      reflect barriers in access to care (P<.001).

PMID- 18086972
TI  - Immune activation by epidermal growth factor receptor specific monoclonal
      antibody therapy for head and neck cancer.
AB  - OBJECTIVE: To determine if the epidermal growth factor receptor (EGFR)-specific
      monoclonal antibodies (mAbs) cetuximab or panitumumab mediate in vitro immune
      activation against squamous cell carcinoma of the head and neck (SCCHN) cell
      lines. DESIGN: In vitro study. SETTING: Basic science research laboratory.
      INTERVENTION: Squamous cell carcinoma of the head and neck cell lines were
      treated with the Food and Drug Administration-approved EGFR-specific mAbs
      cetuximab or panitumumab in the presence or absence of peripheral blood
      mononuclear cells from healthy donors. MAIN OUTCOME MEASURES: Cetuximab and
      panitumumab were compared in terms of their cytotoxic effects, ability to induce
      apoptosis, bind to EGFR, and block phosphorylation of this receptor in SCCHN cell
      lines. RESULTS: We demonstrate that both cetuximab and panitumumab have similar
      levels of EGFR binding, induction of apoptosis, cell lysis, and inhibition of
      phospho-EGFR in SCCHN cell lines, suggesting similar direct effects. However,
      neither of these mAbs demonstrated in vitro antitumor activity when used alone.
      In contrast, in the presence of peripheral blood lymphocytes, either of them can
      mediate antibody-dependent cell cytotoxicity in vitro when used in doses similar
      to those found in patients receiving them clinically. CONCLUSION: We propose that
      antibody-dependent cell cytotoxicity may constitute an important antitumor
      mechanism that could contribute to overall clinical effectiveness of EGFR
      specific antibodies.

PMID- 18086973
TI  - Squamous cell carcinoma from an unknown head and neck primary site: a "selective
      treatment" approach.
AB  - OBJECTIVE: To assess the efficacy of limiting treatment to the involved neck by
      way of neck dissection and adjuvant radiotherapy and reserving other therapies
      for salvage in the management of metastatic cervical squamous cell carcinoma from
      an unknown head and neck primary site. DESIGN: Retrospective study of patients
      whose clinicopathological data had been prospectively collected in a
      comprehensive head and neck database. SETTING: A tertiary referral university
      hospital. PATIENTS: The study population comprised 70 patients with metastatic
      cervical squamous cell carcinoma from an unknown head and neck primary site.
      INTERVENTIONS: Neck dissection alone in patients with pN1 disease confined to the
      lymph node. All remaining patients received neck dissection and adjuvant
      postoperative irradiation of the involved (dissected) neck. MAIN OUTCOME
      MEASURES: Incidence of primary, regional, and distant recurrence and disease
      specific and overall survival. RESULTS: Nodal stage was pN1 in 5 patients (7%);
      pN2a in 13 (19%); pN2b in 30 (43%); pN2c in 4 (6%); and pN3 in 18 (26%). Neck
      dissection alone was performed in 10 patients (14%), while 60 patients (86%)
      underwent neck dissection and adjuvant irradiation. Median follow-up was 45
      months. The primary tumor site emerged in 8 patients (11%). The 5-year control
      rates were 84% in the ipsilateral (dissected) neck and 93% in the contralateral
      (undissected) neck. The 5-year disease-specific and overall survival rates were
      62% and 56%, respectively. Macroscopic extracapsular spread was the only
      statistically significant adverse prognostic factor (P < .001). CONCLUSIONS: The
      results of our selective treatment approach compare favorably with the results of
      other reported protocols using comprehensive irradiation or concurrent
      chemoradiation. However, patients with extracapsular spread and pN2 or pN3
      disease were at high risk of treatment failure and may benefit from adjuvant
      chemoradiation. Although our protocol spares patients of potentially morbid
      therapies, salvage is rarely successful.

PMID- 18086974
TI  - Aspiration in chemoradiated patients with head and neck cancer.
AB  - OBJECTIVE: To review the incidence of aspiration after chemoradiation therapy in
      patients with head and neck cancer (HNC). DESIGN: Retrospective review. SETTING:
      Academic institution. PATIENTS: One hundred thirty patients with advanced HNC
      underwent chemoradiation therapy at our institution between 1998 and 2002 as part
      of a larger, multi-institutional, prospective study of induction chemotherapy
      followed by chemoradiation therapy; the 118 patients (91%) for whom oropharyngeal
      motility (OPM) study data were available are discussed in this article. MAIN
      OUTCOME MEASURES: Incidence of trace (</= 5% of swallowed bolus) and frank (> 5%)
      aspiration (deep laryngeal or tracheal penetration) as determined by pretreatment
      and posttreatment OPM studies and correlation of the findings with the patients'
      reported symptoms. RESULTS: Eighty-one patients (69%) underwent at least 1 OPM
      study demonstrating aspiration within the first year after chemoradiation
      therapy, with 30 (25%) demonstrating frank aspiration. Of the patients who
      aspirated, 61 (75%) reported no symptoms of coughing or choking (80% of trace and
      67% of frank aspirators). The patients with cancer of the larynx and hypopharynx
      were more likely to be aspirators (P = .007 and P = .004, respectively). Of the
      62 patients with available pretreatment OPM data, 33 (53%) demonstrated
      aspiration at baseline. CONCLUSIONS: Aspiration is highly prevalent among
      patients with advanced HNC at baseline and is worse in the posttreatment period
      after chemoradiation therapy. The majority of these patients report no symptoms.
      All patients with advanced HNC should undergo instrumental swallow assessment,
      even in the absence of symptoms, to detect subclinical aspiration and to
      institute therapeutic maneuvers and swallow precautions as well as to determine
      the safety of oral feeding.

PMID- 18086975
TI  - Nasopharyngectomy and surgical margin status: a survival analysis.
AB  - OBJECTIVE: To explore whether the margin status at surgical salvage
      nasopharyngectomy for local residual or recurrent nasopharyngeal carcinoma
      affects patient survival. DESIGN: Retrospective case series review. SETTING:
      Academic tertiary referral center. PATIENTS: Seventy-nine consecutive patients
      with operable local residual or recurrent nasopharyngeal carcinoma after failure
      of primary treatment with radiotherapy with or without chemotherapy underwent
      surgical salvage nasopharyngectomy with curative intent between November 28,
      1987, and November 17, 2003. Sixty-one patients were men and 18 were women. Their
      mean age was 48 years (age range, 26-70 years). INTERVENTION: Surgical salvage
      nasopharyngectomy. MAIN OUTCOME MEASURES: The status of the closest margin at
      surgery was assessed as clear, close, or positive. Survival time was measured
      from the date of surgery to the date of the last follow-up, to the date of an
      event occurrence, or to the date of death. The Kaplan-Meier method was used to
      estimate the probability of local progression-free survival and overall survival
      at 5 years. Differences in survival rates between surgical margin statuses were
      assessed using the log-rank test. RESULTS: Five-year overall survival for
      patients with clear margins was 77%, for patients with close margins was 46% (P =
      .05), and for patients with positive margins was 23% (P < .001). CONCLUSION:
      Clear surgical margins at the time of surgical salvage nasopharyngectomy for
      residual or recurrent nasopharyngeal carcinoma positively affect patient
      survival.

PMID- 18086976
TI  - Evaluation of hardware-related complications in vascularized bone grafts with
      locking mandibular reconstruction plate fixation.
AB  - OBJECTIVE: To identify the incidence of hardware and bone-healing complications
      in patients who underwent locking mandibular reconstruction plate (LMRP) fixation
      of vascularized bone grafts for reconstruction of segmental mandibular defects.
      DESIGN: Case series. SETTING: Academic tertiary care medical center. PATIENTS:
      One hundred one patients who had undergone LMRP fixation of vascularized bone
      grafts for reconstruction of segmental mandibular defects with a minimum follow
      up of 6 months. MAIN OUTCOME MEASURES: Association of patient- and defect-related
      characteristics with the incidence of loose screws, osteosynthesis nonunion, and
      complications necessitating hardware removal. RESULTS: The incidence of loose
      screws was 0.8% in 984 locking screws implanted. The incidence of nonunion was
      0.7% in 290 osteosyntheses. Overall, 15 of 101 LMRPs (14.8%) were removed because
      of hardware-related complications, with plate extrusion (n = 10) the most common
      complication necessitating hardware removal. Pathologic diagnosis (P = .002),
      previous treatment with hyperbaric oxygen (P < .001), radiation therapy (P <
      .001), and cancer recurrence (P = .03) were statistically significant predictors
      of LMRP-related complications at univariate analysis. At multivariate analysis,
      previous treatment with hyperbaric oxygen (P < .046) remained a statistically
      significant predictor of LMRP-related complications. CONCLUSIONS: In patients
      undergoing mandibular reconstruction, LMRPs are highly effective for fixation of
      vascularized bone grafts, with a high incidence of bone-graft healing and a low
      incidence of complications related to loose screws. Nevertheless, there remains a
      15% incidence of hardware-related complications, most related to hardware
      extrusion. Previous treatment with hyperbaric oxygen is a statistically
      significant predictor of LMRP-related complications.

PMID- 18086977
TI  - Patient safety and surgeons: why the resistance?

PMID- 18086978
TI  - Comparison of clinical assessment with ultrasound flow for hemodialysis access
      surveillance.
AB  - HYPOTHESIS: Organized clinical assessment of hemodialysis access is as useful a
      surveillance tool as ultrasound flow measurements in preventing access
      thrombosis. DESIGN: Cohort analysis comparing a dialysis unit evaluated using
      ultrasound flow measurements with another unit evaluated clinically. SETTING:
      University-affiliated community program with private and health maintenance
      organization dialysis units. PATIENTS: One hundred patients in each unit were
      enrolled. Patients who were unavailable for follow-up or died within the first 30
      days of enrollment were excluded from further analysis. INTERVENTION: Angiograms
      were obtained in the Transonics Doppler ultrasound system (Transonics Systems
      Inc, Ithaca, New York) cohort if graft flow was less than 600 mL/min, fistula
      flow was less than 450 mL/min, or flow decreased more than 25%, and in the
      clinical cohort if there was a change in the access appearance, change in the
      bruit, or a sharp increase in venous resistance. MAIN OUTCOME MEASURES: Primary
      and secondary patencies of the hemodialysis access were analyzed for each cohort.
      Subset analysis was obtained for synthetic grafts and native fistulas. Procedures
      were assessed for each cohort. RESULTS: The patients in the clinical cohort had
      similar primary patency (1199 days) as in the Transonics cohort (1162 days) (P =
      .92). Angiographic procedures were also similar, with 56% of all patients having
      none. The mean number of procedures was 0.56 per patient in the Transonics cohort
      and 0.48 in the clinical group (P = .48). CONCLUSION: An organized clinical
      assessment, using a formal tracking tool, is equal to ultrasound flow
      measurements as a surveillance method to prevent hemodialysis access thrombosis.

PMID- 18086979
TI  - Comparison of percutaneous and surgical approaches for radiofrequency ablation of
      small and medium hepatocellular carcinoma.
AB  - HYPOTHESIS: Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) can
      be performed by percutaneous or surgical approach. Tumor size is an important
      consideration while deciding the treatment approach. DESIGN: Case series with
      prospective data collection. SETTING: A tertiary referral center. PATIENTS: A
      total of 228 patients who underwent RFA of small (</= 3 cm; n = 155) and medium
      (3.1-5 cm; n = 73) HCC by percutaneous or surgical approach. MAIN OUTCOME
      MEASURES: Complete ablation rate, post-RFA complications, treatment-related
      mortality, and overall and disease-free survival. RESULTS: In patients with small
      HCC, the complete ablation rate was 95% with both approaches (P > .99).
      Complication rate (P < .001) and hospital stay (P < .001) were higher with the
      surgical approach. One-year and 3-year survival rates were 91% and 71%,
      respectively, in the percutaneous group, and 89% and 57%, respectively, in the
      surgical group (P = .30). In patients with medium HCC, the complete ablation rate
      was similar between the surgical and the percutaneous groups (92% vs 95%; P =
      .48), and the complication rate was also comparable (P = .17). The 1-year and 3
      year survival rates were 92% and 68%, respectively, in the surgical group,
      significantly superior to the corresponding rates of 81% and 42% in the
      percutaneous group (P = .03). CONCLUSIONS: In patients with small HCC, the
      percutaneous approach achieved similar tumor control with lower morbidity
      compared with the surgical approach and should be the preferred approach provided
      that tumor location is suitable. For medium HCC, the surgical approach seems to
      achieve better overall survival and may be a preferred option.

PMID- 18086980
TI  - A second liver resection due to recurrent colorectal liver metastases.
AB  - BACKGROUND: Repeat liver resection because of recurrent colorectal liver
      metastases can provide survival benefit with a low rate of complications. DESIGN:
      Retrospective study. PARTICIPANTS: Forty patients who underwent a second
      hepatectomy because of liver metastases from colorectal cancer. MAIN OUTCOME
      MEASURES: Short- and long-term results of a second hepatectomy and determination
      of prognostic factors. RESULTS: The postoperative mortality rate was 2.5%. The
      postoperative morbidity rate was not significantly different after a second
      hepatectomy compared with single hepatectomy (42.5% and 27.5%, respectively; P =
      .10). Transfusion requirement and hospital stay were comparable for both a single
      and a second hepatectomy. Three- and 5-year overall survival rates were 55% and
      31%, respectively. Disease-free survival rates at 3 and 5 years were,
      respectively, 49% and 27%. The interval between first and second hepatectomies
      and the presence of extrahepatic disease were independently related to survival
      (multivariate analysis). CONCLUSIONS: A second liver resection because of
      recurrent liver metastases from colorectal cancer is safe and provides a survival
      benefit similar to that with single hepatectomy. Our analysis suggests that the
      benefit of treatment is limited in patients who undergo a second hepatectomy
      within 1 year of the first operation and in those with extrahepatic disease.

PMID- 18086981
TI  - Circulating dendritic cells and development of septic complications after
      pancreatectomy for pancreatic cancer.
AB  - OBJECTIVE: To investigate whether circulating dendritic cells in patients with
      pancreatic cancer is a risk factor for septic complications after pancreatectomy.
      DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Forty-one
      patients with pancreatic cancer who underwent pancreatectomy from May 2001 to
      July 2005. Patients were divided into 2 groups depending on whether or not they
      had a development of postoperative septic complications. MAIN OUTCOME MEASURES:
      Dendritic cell, natural killer cell, and CD4(+) T-cell, and CD8(+) T-cell counts
      were measured preoperatively in each patient. Clinicopathologic parameters and
      immune parameters for each patient, operation, and tumor were compared between
      the 2 groups. Preoperative risk factors for postoperative septic complications
      were determined using logistic regression analysis. RESULTS: Circulating
      dendritic cell count before pancreatectomy in patients with septic complications
      postoperatively for pancreatic cancer was significantly lower than in patients
      without septic complications. Multivariate analysis indicated that preoperative
      circulating dendritic cell count was the only predictive value among the diverse
      clinical parameters tested in relation to the development of septic
      complications. Notably, when the circulating dendritic cell count was less than
      10.0 x 10(3)/mL in the peripheral blood, the risk of developing postoperative
      septic complications markedly increased. In such cases, the sensitivity,
      specificity, positive predictive value, and negative predictive value of total
      circulating dendritic cell count were as high as 80%. CONCLUSION: In patients
      with pancreatic cancer, low preoperative circulating dendritic cell count (< 10.0
      x 10(3)/mL) is a significant risk factor for the development of septic
      complications after pancreatectomy.

PMID- 18086982
TI  - Acute postoperative pain management using massage as an adjuvant therapy: a
      randomized trial.
AB  - HYPOTHESIS: Adjuvant massage therapy improves pain management and postoperative
      anxiety among many patients who experience unrelieved postoperative pain.
      Pharmacologic interventions alone may not address all of the factors involved in
      the experience of pain. DESIGN: Randomized controlled trial. SETTING: Department
      of Veterans Affairs hospitals in Ann Arbor, Michigan, and Indianapolis, Indiana.
      PATIENTS: Six hundred five veterans (mean age, 64 years) undergoing major surgery
      from February 1, 2003, through January 31, 2005. INTERVENTIONS: Patients were
      assigned to the following 3 groups: (1) control (routine care), (2)
      individualized attention from a massage therapist (20 minutes), or (3) back
      massage by a massage therapist each evening for up to 5 postoperative days. Main
      Outcome Measure Short- and long-term (> 4 days) pain intensity, pain
      unpleasantness, and anxiety measured by visual analog scales. RESULTS: Compared
      with the control group, patients in the massage group experienced short-term
      (preintervention vs postintervention) decreases in pain intensity (P = .001),
      pain unpleasantness (P < .001), and anxiety (P = .007). In addition, patients in
      the massage group experienced a faster rate of decrease in pain intensity (P =
      .02) and unpleasantness (P = .01) during the first 4 postoperative days compared
      with the control group. There were no differences in the rates of decrease in
      long-term anxiety, length of stay, opiate use, or complications across the 3
      groups. CONCLUSION: Massage is an effective and safe adjuvant therapy for the
      relief of acute postoperative pain in patients undergoing major operations.

PMID- 18086983
TI  - Detection of new tumors by intraoperative ultrasonography during repeated hepatic
      resections for hepatocellular carcinoma.
AB  - OBJECTIVE: To evaluate the efficacy of intraoperative (IO) ultrasonography (US)
      as compared with other imaging modalities on the primary and repeated
      hepatectomies for hepatocellular carcinoma. DESIGN: Retrospective study. SETTING:
      University hospital. PATIENTS: From January 6, 1995, to December 26, 2002, 430
      patients underwent 555 operations for hepatocellular carcinoma. MAIN OUTCOME
      MEASURES: New tumors detected by IOUS at the primary and second hepatectomies
      were analyzed. The long-term outcomes were also studied. RESULTS: Intraoperative
      US sensitivity was the highest. The detection rate by each imaging modality
      slightly but uniformly decreased at the second hepatectomy. Intraoperative US
      detected 56 new tumors in 30 cases (7.0%) at the primary hepatectomy and 13 new
      tumors in 8 cases (7.3%) at the second hepatectomy. The mean +/- SD tumor sizes
      were 8.7 +/- 3.8 mm and 9.0 +/- 5.2 mm at the primary and second resections,
      respectively. The preoperative surgical plan was changed owing to the IOUS
      findings alone in 24 cases (5.6%) at the primary hepatectomy and in 7 cases
      (6.4%) at the second. Although recurrence was frequent in patients with new
      tumors at the primary hepatectomy, long-term survival after appropriate treatment
      for recurrence was similar to that of patients without new tumors. CONCLUSIONS:
      Despite the recent progress in imaging modalities, IOUS is still the most
      sensitive. The same degree of precaution is necessary for new tumors when
      performing IOUS during repeated hepatectomy. Patients with new tumors are at high
      risk for recurrence, so regular follow-up is important to prolong survival.

PMID- 18086984
TI  - Postoperative robotic telerounding: a multicenter randomized assessment of
      patient outcomes and satisfaction.
AB  - HYPOTHESIS: Patient safety and satisfaction are adversely affected when robotic
      videoconferencing (telerounding) is used in the postoperative setting. DESIGN:
      Randomized controlled trial. SETTING: Three academic institutions. PATIENTS: A
      total of 270 adults undergoing a urologic procedure requiring a hospital stay of
      24 to 72 hours were randomized to receive either traditional bedside rounds or
      robotic telerounds. MAIN OUTCOME MEASURES: The primary outcome measure was
      postoperative patient morbidity. Secondary outcomes were patient-reported
      satisfaction and hospital length of stay. Other variables assessed included
      demographics, procedure, operative time, estimated blood loss, and mortality.
      Patients also completed a validated satisfaction instrument 2 weeks after
      hospital discharge. RESULTS: Patients were equally distributed based on the
      baseline demographic and operative measures. Morbidity rates were similar between
      the study arms (standard rounds vs telerounds: 16% vs 13%; P = .64). Length of
      stay was similar in both arms (standard rounds vs telerounds: 2.8 vs 2.8 days; P
      = .94). In addition, patient satisfaction was equivalently high in both arms of
      the study. CONCLUSIONS: Robotic telerounds matched the performance of standard
      bedside rounds after urologic surgical procedures. Virtual visits did not result
      in missed or increased postoperative complications. Hospital length of stay and
      ratings of hospital satisfaction were on par with those for traditional rounding.

PMID- 18086985
TI  - Predictive value of age and serum parathormone and vitamin d3 levels for
      postoperative hypocalcemia after total thyroidectomy for nontoxic multinodular
      goiter.
AB  - HYPOTHESIS: Age, postoperative serum parathormone (PTH) level, and preoperative
      serum 25-hydroxyvitamin D(3) (25-OHD) level predict postoperative hypocalcemia
      after total thyroidectomy. DESIGN: Prospective clinical trial. SETTING: Tertiary
      referral center. PATIENTS: One hundred thirty patients with nontoxic multinodular
      goiter. Patients were divided into 2 groups according to the postoperative serum
      calcium level. Group 1 (n = 32) consisted of patients with a postoperative serum
      calcium level of 8 mg/dL or less, and group 2 (n = 98) consisted of patients with
      a postoperative serum calcium level higher than 8 mg/dL. INTERVENTIONS: The
      preoperative serum 25-OHD level and preoperative and postoperative serum calcium
      and PTH levels were determined. MAIN OUTCOME MEASURES: The number of patients
      developing hypocalcemia and prediction of postoperative hypocalcemia by the serum
      25-OHD and PTH levels. RESULTS: Hypocalcemia developed in 32 patients (24.6%)
      (group 1). The preoperative serum 25-OHD level and postoperative serum calcium
      and PTH levels in group 1 were significantly lower than in group 2 (P = .001).
      With logistic regression analysis, factors that were predictive of postoperative
      hypocalcemia included a preoperative serum 25-OHD level less than 15 ng/mL (P <
      .001; odds ratio, 558.5), a postoperative serum PTH level less than 10 pg/mL (P =
      .01; odds ratio, 16.4), and being older than 50 years (P = .01; odds ratio, 4.6).
      CONCLUSIONS: Age, a low preoperative serum 25-OHD level, and a low postoperative
      serum PTH level are significantly associated with postoperative hypocalcemia. The
      low preoperative serum 25-OHD level was more significant than the low
      postoperative serum PTH level in the prediction of postoperative hypocalcemia.

PMID- 18086986
TI  - Laparoscopic liver resection for benign disease.
AB  - HYPOTHESIS: Resection for benign liver disease can represent a valid indication
      for the laparoscopic approach. DESIGN: Prospective case series. SETTING: Tertiary
      referral center. PATIENTS: Fifty patients with benign disease underwent
      laparoscopic liver resection. Indications for resection included preoperative
      diagnosis of adenoma or cystadenoma, uncertain preoperative diagnosis, and
      presence of symptoms. Inclusion criteria were lesions 5 cm or less located in the
      peripheral segments (segments 2-6). INTERVENTION: Laparoscopic liver resection
      using a surgical technique including 5 ports, harmonic transection, stapling of
      large vessels, and extraction in a bag through a separate incision. MAIN OUTCOME
      MEASURES: Intraoperative results and postoperative morbidity. RESULTS: Thirty
      five patients (70%) presented with solid tumor; 11 (22%), with cystic lesions;
      and 4 (8%), with biliary disease. Tumor was solitary in 41 cases (82%) and
      multiple in 9 (18%). Mean (SD) surgical time was 191 (77.5) minutes (range, 30
      480 minutes). There were 4 conversions (8%) and 1 patient received a transfusion
      (2%). There was no mortality. The postoperative morbidity rate was 10% and
      included only nonspecific complications. Median hospital stay was 5 days.
      CONCLUSIONS: Laparoscopic liver resection for benign disease can be recommended
      in patients with peripheral lesions requiring limited resection. Major resections
      may be performed in highly select patients but require further evaluation.
      Specific training is required. Indications for laparoscopic resection of benign
      liver disease must be the same as those for open surgery. Reduction of abdominal
      wall damage and cosmetic advantages of the laparoscopic approach represent a
      clear benefit in patients with benign liver disease.

PMID- 18086987
TI  - Timing of surgical intervention in necrotizing pancreatitis.
AB  - OBJECTIVE: To determine the effect of timing of surgical intervention for
      necrotizing pancreatitis. DESIGN: Retrospective study of 53 patients and a
      systematic review. SETTING: A tertiary referral center. Main Outcome Measure
      Mortality. RESULTS: Median timing of the intervention was 28 days. Eighty-three
      percent of patients had infected necrosis and 55% had preoperative organ failure.
      The mortality rate was 36%. Sixteen patients were operated on within 14 days of
      initial admission, 11 patients from day 15 to 29, and 26 patients on day 30 or
      later. This latter group received preoperative antibiotics for a longer period (P
      < .001), and Candida species and antibiotic-resistant organisms were more often
      cultured from the pancreatic or peripancreatic necrosis in these patients (P =
      .02). The 30-day group also had the lowest mortality (8% vs 75% in the 1 to 14
      days group and 45% in the 15 to 29-days group, P < .001); this difference
      persisted when outcome was stratified for preoperative organ failure. During the
      second half of the study, necrosectomy was further postponed (43 vs 20 days, P =
      .06) and mortality decreased (22% vs 47%, P = .09). We also reviewed 11 studies
      with a total of 1136 patients. Median surgical patient volume was 8.3 patients
      per year (range, 5.3-15.6), median timing of surgical intervention was 26 days
      (range, 3-31), and median mortality was 25% (range, 6%-56%). We observed a
      significant correlation between timing of intervention and mortality (R = -
      0.603; 95% confidence interval, - 2.10 to - 0.02; P = .05). CONCLUSION:
      Postponing necrosectomy until 30 days after initial hospital admission is
      associated with decreased mortality, prolonged use of antibiotics, and increased
      incidence of Candida species and antibiotic-resistant organisms.

PMID- 18086988
TI  - Laparoscopic enucleation of insulinomas.
AB  - HYPOTHESIS: Laparoscopic enucleation of insulinomas is safe and effective and is
      associated with a short hospital stay. DESIGN: Case series identified through
      retrospective review of medical records. SETTING: University of California, San
      Francisco Medical Center, a tertiary care referral hospital. PATIENTS: Nine
      patients with insulinomas that were thought to be suitable for laparoscopic
      enucleation. INTERVENTION: Laparoscopic enucleation of solitary insulinomas of
      the pancreas. MAIN OUTCOME MEASURES: Successful enucleation, conversion to open
      operation, postoperative complications, and duration of hospitalization. RESULTS:
      Seven of 9 patients had curative laparoscopic enucleations of insulinomas. In the
      2 other patients, the laparoscopic approach was converted to an open operation to
      perform a distal pancreatectomy. All patients were cured. Computed tomography
      (CT) localized the tumor in 5 of 9 patients; laparoscopic enucleation was
      successful in all 5. Endoscopic ultrasonography correctly identified the lesions
      in 2 of 3 patients with nondiagnostic CT scans. Both lesions were successfully
      enucleated laparoscopically. Postoperative pancreatic fistulas occurred in 7 of 9
      patients, but they caused little morbidity. No patient required another
      operation. Five of 7 patients treated laparoscopically were discharged to home on
      the first postoperative day. CONCLUSIONS: Laparoscopic enucleation was safe and
      effective. If the lesion was seen on CT, it could be removed laparoscopically.
      Endoscopic ultrasonography was useful for identifying lesions in patients whose
      CT scans were nondiagnostic. Pancreatic fistulas were common, but they resolved
      spontaneously and produced little morbidity. Laparoscopic enucleation resulted in
      a short hospitalization and rapid recovery for most patients.

PMID- 18086989
TI  - Emergency parotidectomy for penetrating zone III neck trauma.
AB  - Penetrating trauma to the face and upper zone III of the neck may present unique
      challenges when the parotid gland and associated neurovascular structures are
      involved. We report a case of massive hemorrhage from penetrating neck trauma
      that necessitated emergency parotidectomy for vascular exposure. Facial nerve
      repair was also necessary, underscoring the importance of this approach not only
      for successful vascular control but also for preservation of nearby vital
      structures. The management of penetrating trauma to the parotid region,and
      relevant anatomy, are discussed.

PMID- 18086990
TI  - Meta-analysis of short-term outcomes of randomized controlled trials of LigaSure
      vs conventional hemorrhoidectomy.
AB  - OBJECTIVE: To evaluate the short-term outcomes of hemorrhoidectomy performed
      using the LigaSure vessel sealing device (Valleylab, Boulder, Colorado) or the
      conventional approach. DATA SOURCES: MEDLINE, EMBASE, Ovid, and Cochrane
      databases for studies published between 2002 and 2006. STUDY SELECTION:
      Randomized controlled trials published between 2002 and 2006 comparing short-term
      outcomes for LigaSure vs conventional hemorrhoidectomy. DATA EXTRACTION:
      Operative parameters, short-term complications, and postoperative recovery.
      Trials were assessed using a modified Jadad score. Random-effects meta-analytical
      techniques were used in the analysis. DATA SYNTHESIS: Nine randomized controlled
      trials with matched selection criteria reporting on 525 patients, of whom 266
      (50.7%) underwent LigaSure and 259 (49.3%) underwent conventional
      hemorrhoidectomy. Operative time (weighted mean difference [WMD], - 8.67 minutes;
      95% confidence interval [CI], - 15.34 to - 2.00 minutes), blood loss (WMD, -
      23.08 mL; 95% CI, - 27.24 to - 18.92 mL), and pain the day after the operation
      measured by the visual analog scale (WMD, - 2.31; 95% CI, - 3.37 to - 1.26) were
      significantly reduced following LigaSure hemorrhoidectomy. There was a decrease
      in time taken to return to work or normal activity (WMD, - 3.49 days; 95% CI, -
      7.40 to 0.43), which was of marginal significance (P = .08). Incidence of
      postoperative hemorrhage was comparable as was incidence of anal stenosis and
      fecal and flatus incontinence between the 2 groups. CONCLUSIONS: LigaSure
      hemorrhoidectomy results in a significant reduction in operative time and blood
      loss, but it may not confer any advantage over the conventional operation in
      terms of postoperative pain, length of hospital stay, or time taken to return to
      work or normal activity. The expediency of the device must be weighed against its
      additional cost. Long-term evaluation of outcomes and morbidity are still needed.

PMID- 18086991
TI  - Image of the month--quiz case. Tuberculous peritonitis.

PMID- 18086992
TI  - Image of the month--quiz case. Intussuscepted transverse colonic lipoma.

PMID- 18086993
TI  - Reduced renal and hepatic perfusion caused by pos-itive-pressure
      pneumoperitoneum: impact on donor kidneys.

PMID- 18086994
TI  - Making better cents of future teaching hospital costs.

PMID- 18086996
TI  - Fractional resurfacing: a new therapeutic modality for Becker's nevus.

PMID- 18086997
TI  - The risk of mortality in patients with psoriasis: results from a population-based
      study.
AB  - OBJECTIVE: To determine the risk of mortality in patients with psoriasis. DESIGN:
      Cohort study. SETTING: General practitioners participating in the General
      Practice Research Database in the United Kingdom, 1987-2002. PATIENTS: Mild
      psoriasis, defined as any patient with a diagnostic code of psoriasis but no
      history of systemic therapy; severe psoriasis, any patient with a diagnostic code
      of psoriasis and a history of systemic therapy consistent with severe psoriasis.
      The unexposed (control) population was composed of patients with no history of a
      psoriasis diagnostic code. Control patients were selected in a 5:1 ratio from the
      same practice and date in practice as the patients with psoriasis. MAIN OUTCOME
      MEASURE: Hazard ratio (HR) of time to death using Cox proportional hazards models
      adjusted for age and sex. RESULTS: There was no overall effect of mild psoriasis
      on mortality (HR, 1.0; 95% confidence interval [CI], 0.97-1.02), whereas patients
      with severe psoriasis demonstrated an increased overall mortality risk (HR, 1.5;
      95% CI, 1.3-1.7). The association of severe psoriasis with mortality persisted
      after adjustment for risk factors for mortality (HR, 1.4; 95% CI, 1.3-1.6) and
      after exclusion of patients with inflammatory arthropathy (HR, 1.5; 95% CI, 1.3
      1.8). Male and female patients with severe psoriasis died 3.5 (95% CI, 1.2-5.8)
      and 4.4 (95% CI, 2.2-6.6) years younger, respectively, than patients without
      psoriasis (P < .001). CONCLUSION: Severe but not mild psoriasis is associated
      with an increased risk of death.

PMID- 18086998
TI  - A 3-year causative study of pompholyx in 120 patients.
AB  - OBJECTIVE: To assess the relative frequency of the different causes of pompholyx
      evoked in the literature. DESIGN: Prospective survey. SETTING: Clinical
      outpatient setting. PATIENTS: A total of 120 consecutive patients with pompholyx
      referred to our department from 2000 through 2003. MAIN OUTCOME MEASURES:
      Systematic investigation of different causes of pompholyx: fungal intertrigo,
      hyperhidrosis, atopy, contact eczema, and internal reactions with systematic
      provocation tests to metals, balsam of Peru, and food allergen when suspected.
      RESULTS: The present study found the following causes of pompholyx in the 120
      patients: mycosis (10.0%); allergic contact pompholyx (67.5%), with cosmetic and
      hygiene products as the main factor (31.7%), followed by metals (16.7%); and
      internal reactivation from drug, food, or haptenic (nickel) origin (6.7%). The
      remaining 15.0% of patients were classified as idiopathic patients, but all were
      atopic. (Percentages do not total 100 because of rounding.) CONCLUSIONS: Our data
      confirm the existence of reactional pompholyx to interdigital-plantar intertrigos
      and endogenous reactions to metals or other allergens, but they mainly point at
      the unexpected importance of a so-called contact pompholyx in which cosmetic and
      hygiene products play a preponderant role compared with metals. The great
      frequency of atopic conditions, even if idiopathic pompholyx is not inferred as
      an equivalent of atopy, should lead to further causative investigations before
      undertaking more expensive or extensive treatments of refractory pompholyx.

PMID- 18086999
TI  - Teledermatological monitoring of leg ulcers in cooperation with home care nurses.
AB  - OBJECTIVES: To examine the feasibility and acceptance of teledermatology for
      wound management for patients with leg ulcers by home care nurses and evaluate
      the reduction of costs and the acceptance of teledermatology by patients and home
      care nurses. DESIGN: Case series of telemonitored patients with leg ulcers
      including cost-effectiveness analysis. SETTING: Home monitoring by home care
      nurses. PATIENTS: Sixteen patients with 45 leg ulcers of different origin were
      included. MAIN OUTCOME MEASURES: After an initial outpatient visit when the leg
      ulcers were assessed and classified, teledermatological follow-up was done by
      home care nurses. Relevant clinical information and 1 to 4 digital images of the
      wound and surrounding skin were transmitted weekly via a secure Web site to an
      expert at the wound care center, who assessed the wound and made therapeutic
      recommendations. RESULTS: Of the 707 images transmitted for teleconsultation, in
      644 (89%) the quality of the images was excellent or sufficient and the experts
      were confident in giving therapeutic recommendations. Of the 45 ulcers, 32 (71%)
      decreased in size and 14 (31%) healed completely, whereas 10 of the 45 ulcers
      (22%) increased slightly in size despite the teledermatological monitoring. In 3
      ulcers (7%), no measurement was possible owing to the overly large size of the
      ulcers. The acceptance of telemedicine was very good by most patients. Of 15 home
      care nurses working in the district, 7 were very satisfied with
      teledermatological monitoring of wound care. There was a reduction of 46% in
      transportation costs for the insurance companies as well as for the patients
      owing to a significant decrease in the number of visits to general physicians or
      the wound care center. CONCLUSIONS: The acceptance of teledermatological
      monitoring of wound care was very high by patients, home care nurses, and wound
      experts. Decreased health care costs by reducing the number of visits to wound
      care centers or specialist physicians and improvement in quality of life for
      patients with leg ulcers using telemedicine seems possible. Teledermatology
      offers great potential for long-term wound care.

PMID- 18087000
TI  - Reliability of the Roenigk classification of liver damage after methotrexate
      treatment for psoriasis: a clinicopathologic study of 160 liver biopsy specimens.
AB  - OBJECTIVE: To determine the interobserver reliability of the Roenigk score as a
      classification system of liver damage and its possible consequences for clinical
      practice. DESIGN: Retrospective study. SETTING: Academic research. Patients One
      hundred sixty liver biopsy specimens from patients with psoriasis receiving
      methotrexate treatment were rereviewed and analyzed blindly by an experienced
      pathologist with an interest in liver pathologic conditions. Main Outcome Measure
      Interobserver variation was evaluated using kappa statistics. RESULTS: A high
      concordance was present in the evaluation of the Roenigk grade of fibrosis
      (weighted kappa = 0.73; 95% confidence interval, 0.63-0.83). Agreement was good
      regarding the number of biopsy specimens for patients whose clinical management
      should be changed (kappa = 0.71; 95% confidence interval, 0.56-0.87). Conclusion
      The Roenigk classification in the assessment of liver fibrosis is a reliable
      scoring system.

PMID- 18087001
TI  - Results of radiotherapy in 153 primary cutaneous B-Cell lymphomas classified
      according to the WHO-EORTC classification.
AB  - OBJECTIVE: To evaluate the results of radiotherapy in patients with primary
      cutaneous B-cell lymphoma (CBCL) classified according to the criteria of the
      World Health Organization-European Organization for Research and Treatment of
      Cancer (WHO-EORTC) classification. DESIGN: Multicenter, 20-year, retrospective,
      cohort analysis. SETTING: Eight dermatology departments collaborating in the
      Dutch Cutaneous Lymphoma Group. PATIENTS: From 1985 until 2005, a total of 153
      patients with CBCL were initially treated with radiotherapy with curative intent.
      These cases were classified according to the WHO-EORTC classification and
      consisted of 25 primary cutaneous marginal zone lymphomas (PCMZLs), 101 primary
      cutaneous follicle center lymphomas (PCFCLs), and 27 primary cutaneous large B
      cell lymphomas, leg type (PCLBCLs, LT). Interventions Local radiotherapy with a
      median dose of 40 Gy (range, 20-46 Gy) applied to all visible skin lesions. MAIN
      OUTCOME MEASURES: Complete remission rate, relapse rate, 5-year relapse-free
      survival, 5-year overall survival, and 5-year disease-specific survival. RESULTS:
      Complete remission was reached in 151 of 153 patients (99%). Relapse rates for
      PCMZL, PCFCL, and PCLBCL, LT were 60%, 29%, and 64%, and the 5-year disease
      specific survival was 95%, 97%, and 59%, respectively. The PCFCLs presenting on
      the legs had a higher relapse rate (63%) and a much lower 5-year disease-specific
      survival (44%) than PCFCLs at other sites (relapse rate, 25%; 5-year disease
      specific survival, 99%). CONCLUSIONS: Radiotherapy is a suitable treatment for a
      large group of patients with CBCL. However, patients with PCFCL presenting with
      lesions on the leg and patients with PCLBCL, LT display a more unfavorable
      clinical course and should therefore be treated with more aggressive treatment
      modalities.

PMID- 18087002
TI  - Angiogenesis in cutaneous lesions of leprosy: implications for treatment.
AB  - OBJECTIVE: To examine the potential role of angiogenesis in leprosy. DESIGN:
      Immunohistochemical analysis of leprosy lesions. SETTING: Department of
      Dermatology, Venereology, and Leprology, Kasturba Medical College; Division of
      Dermatology, University of California at Los Angeles; and Departments of
      Dermatology and Pathology, Emory University. PATIENTS: Thirty-two cutaneous
      lesions that represented the spectrum of leprosy were obtained from 32 patients.
      MAIN OUTCOME MEASURE: CD31 microvessel counts. RESULTS: The mean CD31 microvessel
      count in borderline tuberculoid, midborderline, and lepromatous leprosy lesions
      was significantly higher than in indeterminate leprosy lesions. CONCLUSIONS:
      Increased bacterial load is associated with increased angiogenesis. Angiogenesis
      inhibitors may be of benefit in the treatment of leprosy.

PMID- 18087003
TI  - Patterns of indoor tanning use: implications for clinical interventions.
AB  - OBJECTIVE: To identify indoor tanning patterns with relevance for health
      screening and prevention efforts. DESIGN: We collected data on indoor tanning
      patterns from January 17, 2006, through April 14, 2006. By cluster analysis, 4
      patterns of indoor tanning were identified: special event, spontaneous or mood,
      mixed, and regular year-round tanning. These 4 types of indoor tanning were
      compared by demographic, behavioral, and psychosocial variables for clinically
      significant differences. SETTING: Midsized (ie, approximately 12 000 students)
      southeastern university. PARTICIPANTS: A total of 168 women who tanned indoors.
      MAIN OUTCOME MEASURES: Self-reported attitudes, intentions and tanning behaviors,
      and tanning dependence. RESULTS: Event tanners tanned the least, started tanning
      the latest, and scored lowest on measures of attitudes, social norms, and tanning
      dependence measures. Regular year-round tanners started the earliest, tanned at
      the highest levels, and scored the highest on the attitude, social norms, and
      tanning dependence measures. Spontaneous or mood tanners were similar to event
      tanners but with a mood component to their tanning. Mixed tanners, as the name
      implies, exhibited behavior that appeared to be a mixture of the regular and
      event tanning types. CONCLUSIONS: The results of this study emphasize the fact
      that "one size fits all" does not apply when it comes to indoor tanning. Tanning
      behavioral types, which can be clinically assessed, can serve as a guide to
      physicians so that they can tailor their skin cancer prevention messages to be
      more effective.

PMID- 18087005
TI  - Smoking and skin aging in identical twins.
AB  - BACKGROUND: A twin pair can provide a rare opportunity to control for genetic
      susceptibility and exposure variables, which often serve as major confounders in
      population-based studies on the relationship between smoking and skin aging.
      OBSERVATIONS: We describe a unique twin pair who spent not only their first 2
      decades of life together but also in their later decades had the same type of job
      at the same latitude, resulting in well-matched levels of significant sun
      exposure. However, the twins differed markedly in regard to smoking history; the
      twin with an approximately 52.5-pack-year smoking history showed more severe skin
      aging than did the nonsmoking twin. CONCLUSION: The difference in skin aging
      illustrated by this twin pair may serve as a motivator for smoking cessation.

PMID- 18087004
TI  - A comparison of oral methylprednisolone plus azathioprine or mycophenolate
      mofetil for the treatment of bullous pemphigoid.
AB  - OBJECTIVE: To investigate the safety and efficacy of oral methylprednisolone
      combined with azathioprine sodium or mycophenolate mofetil for the treatment of
      bullous pemphigoid. DESIGN: A prospective, multicenter, randomized, nonblinded
      clinical trial to compare 2 parallel groups of patients with bullous pemphigoid
      undergoing different treatments. SETTING: Thirteen departments of dermatology in
      Germany. PATIENTS: Patients with bullous pemphigoid (n = 73) as evidenced by
      clinical lesions suggestive of bullous pemphigoid, signs of subepidermal
      blistering on histologic analysis of skin biopsy specimens, linear deposition of
      IgG and C3 along the dermoepidermal junction, and deposition of autoantibodies at
      the blister roof in split-skin analysis. INTERVENTIONS: Treatment with oral
      methylprednisolone plus azathioprine (azathioprine group) or oral
      methylprednisolone plus mycophenolate mofetil (mycophenolate mofetil group). MAIN
      OUTCOME MEASURES: The cumulative total methylprednisolone doses and rates of
      remission. Secondary outcome measures were safety profiles and duration of
      remission. RESULTS: In 38 of 38 patients in the azathioprine group (100%),
      complete remission was achieved after a mean +/- SD of 23.8 +/- 18.9 days vs 42.0
      +/- 55.3 days for 35 of 35 patients in the mycophenolate mofetil group (100%). In
      the azathioprine group, the median +/- SD total cumulative methylprednisolone
      dose used was 4967.0 +/- 12 190.7 mg vs 5754.0 +/- 9692.8 mg in the mycophenolate
      mofetil group. Nine of 38 patients in the azathioprine group (24%) experienced
      grade 3 or 4 adverse effects vs 6 of 35 patients in the mycophenolate mofetil
      group (17%). Azathioprine therapy induced significantly elevated liver function
      test results compared with mycophenolate mofetil (P < .001). Importantly,
      patients in the azathioprine group showed significantly higher toxicity grades
      for aspartate aminotransferase (P = .03), alanine aminotransferase (P = .03), and
      gamma-glutamyltransferase (P = .01) than did those in the mycophenolate mofetil
      group. CONCLUSIONS: Mycophenolate mofetil or azathioprine demonstrate similar
      efficacy during treatment of bullous pemphigoid, and similar cumulative
      corticosteroid doses were given in both treatment arms to control disease.
      However, mycophenolate mofetil showed a significantly lower liver toxicity
      profile than azathioprine therapy.

PMID- 18087006
TI  - Ex vivo dermoscopy of melanocytic tumors: time for dermatopathologists to learn
      dermoscopy.
AB  - BACKGROUND: We have identified cases of skin cancer with discordances between
      clinical, dermoscopic, and histopathologic findings that were likely due to
      sampling errors in the pathology laboratory. This has prompted us to explore the
      use of ex vivo dermoscopy as an ancillary method of gross pathology, which may
      serve to guide tissue sectioning. Noncontact polarized dermoscopy was applied to
      pigmented lesions before excision and at least 6 hours after specimen fixation in
      formalin. OBSERVATIONS: The orientation of the lesion, overall dermoscopic
      pattern, and dermoscopic pigmented structures (network, globules, and peripheral
      streaks) were readily correlated between the in vivo and ex vivo images for 2
      melanomas and 4 dysplastic nevi. Blood vessels were not observed in the ex vivo
      dermoscopic images, which limited their correlation with the in vivo dermoscopic
      images for basal cell carcinoma. CONCLUSIONS: Dermoscopy can be applied to fixed
      tissues, with findings comparable to those of in vivo examination. This
      observation may serve as the first step toward using dermoscopy to guide tissue
      sectioning in gross pathology.

PMID- 18087007
TI  - Long-term follow-up of a patient with eruptive melanocytic nevi after Stevens
      Johnson syndrome.
AB  - BACKGROUND: Eruptive melanocytic nevi (MN) are a rare phenomenon characterized by
      the simultaneous, abrupt onset of hundreds of MN, often in a grouped
      distribution. There are few studies on this topic in the literature. We followed
      up a patient who developed eruptive MN 38 years ago after Stevens-Johnson
      syndrome. Herein we document this patient's progress and review the literature on
      this unusual phenomenon. OBSERVATIONS: For 38 years, the patient's lesions have
      remained stable, without signs of malignant degeneration. We discuss the possible
      etiology and natural history of this condition in 2 major patient populations:
      those with bullous disorders and those with systemic immunosuppression.
      CONCLUSIONS: We postulate that the etiology and natural course of eruptive MN may
      differ between the 2 main populations of patients at risk for eruptive MN, with
      MN arising after bullous disorders being more likely to remain benign compared
      with those in patients with ongoing immunosuppression. However, this hypothesis
      has yet to be proved, and it will require long-term surveillance of individuals
      who have developed eruptive MN to determine its merit.

PMID- 18087008
TI  - Incidence and risk factors for psoriasis in the general population.
AB  - OBJECTIVES: To study the clinical spectrum of psoriasis and the incidence in the
      general population and to identify risk factors associated with the occurrence of
      psoriasis. DESIGN: Prospective cohort study with nested case-control analysis.
      SETTING: The data source was the United Kingdom General Practice Research
      Database containing computerized clinical information entered by general
      practitioners (GPs). PATIENTS: The study population comprised patients receiving
      a first-ever diagnosis of psoriasis between January 1, 1996, and December 31,
      1997, and free of cancer. INTERVENTIONS: Diagnosis of psoriasis was validated in
      a random sample of 14% of all ascertained cases requesting confirmation by the
      GPs. Nested case-control analysis included 3994 cases of psoriasis and a random
      sample of 10 000 controls frequency matched to cases by age, sex, and calendar
      year. MAIN OUTCOME MEASURES: Incidence rate of psoriasis and estimates of the
      odds ratio (OR) and 95% confidence interval (CI) for psoriasis as associated with
      selected risk factors. RESULTS: The incidence rate of psoriasis was 14 per 10 000
      person-years. Patients with antecedents of skin disorders and skin infection
      within the last year carried the highest risk of developing psoriasis (OR, 3.6
      [95% CI, 3.2-4.1], and OR, 2.1 [95% CI, 1.8-2.4], respectively). Also, smoking
      was found to be an independent risk factors for psoriasis (OR, 1.4 [95% CI, 1.3
      1.6]). We did not find an association between risk of psoriasis and antecedents
      of stress, diabetes, hypertension, hyperlipidemia, cardiovascular disease, or
      rheumatoid arthritis. CONCLUSIONS: The incidence rate in our study was higher
      than those published in other studies, probably owing to our case definition that
      considered cases recorded by the GPs independently of a specialist confirmation.
      Our results confirm the association between psoriasis, skin disorders, and
      smoking.

PMID- 18087009
TI  - Level of agreement with the British guidelines for the use of biological
      therapies for psoriasis.

PMID- 18087010
TI  - The role of furry pets in eczema: a systematic review.
AB  - OBJECTIVE: To systematically search, summarize, and critically appraise the
      literature to examine whether pet exposure in early life is associated with an
      increased risk of eczema. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE
      (1950 to June 2006) supplemented by citation lists in retrieved articles and
      contact with researchers. No language restrictions were imposed. DATA EXTRACTION:
      Cohort studies were sufficiently similar to allow pooled analysis. Meta-analysis
      was not possible for cross-sectional studies owing to differences in methods and
      populations. MAIN OUTCOME MEASURES: Incidence or prevalence of eczema. RESULTS:
      Evidence from longitudinal studies showed that previous exposure to cats (pooled
      odds ratio [OR], 0.76; 95% confidence interval [CI], 0.62-0.92), dogs (pooled OR,
      0.68; 95% CI, 0.53-0.87), or "any furry pet" (pooled OR, 0.79; 95% CI, 0.74-0.84)
      is associated with a lower risk of eczema. However, in the only cohort study
      adjusted for avoidance behavior, this "protective effect" disappeared (for cats:
      OR, 0.80; 95% CI, 0.33-1.97). Stratified analysis by family history in 2 birth
      cohort studies showed that dog exposure was protective in patients with atopic
      families. For cats, 1 study showed reduced risk in atopic families only; the
      other study showed no effect. Eight cross-sectional studies evaluated past pet
      exposure; a protective effect was seen in 3 studies for cat, dog, or any pet; no
      study demonstrated an increased risk. CONCLUSIONS: There was no clear evidence
      that early pet exposure is associated with increased risks of subsequent eczema.
      We found some evidence of a possible protective effect of early pet exposure, but
      this might be explained by avoidance behavior in high-risk families.

PMID- 18087011
TI  - Acute and recurrent vesicular hand dermatitis not pompholyx or dyshidrosis.

PMID- 18087012
TI  - Teledermatology: extending specialty care beyond borders.

PMID- 18087013
TI  - Soft papules and nodules on the buttock.

PMID- 18087014
TI  - A firm papule on the lateral tongue.

PMID- 18087015
TI  - Generalized papules in a patient with acute myeloid leukemia.

PMID- 18087016
TI  - Solitary cutaneous nodule in an immunocompromised patient.

PMID- 18087017
TI  - Discoid and subacute lupus erythematosus treated with 0.5% R-salbutamol cream.

PMID- 18087018
TI  - Quality of dermatologic care delivered by physician assistants: an analysis of
      prescribing behavior for the combination antifungal agent clotrimazole
      betamethasone.

PMID- 18087019
TI  - High procalcitonin levels in patients with severe drug reactions.

PMID- 18087020
TI  - Quality of care from a patient's perspective.

PMID- 18087021
TI  - Psoriasiform eruptions during anti TNF-alpha treatment: psoriasis or not?

PMID- 18087022
TI  - British guidelines on the use of biological therapies for psoriasis: a note of
      clarification on the role of etanercept.

PMID- 18087023
TI  - Multiple subcutaneous lipomas induced by HAART in the absence of protease
      inhibitors.

PMID- 18087024
TI  - Clinical improvement of pityriasis rubra pilaris with combination etanercept and
      acitretin therapy.

PMID- 18087025
TI  - A case of zosteriform pigmented purpuric dermatosis.

PMID- 18087026
TI  - Subungual melanoma in situ in a Hispanic girl treated with functional resection
      and reconstruction with onychocutaneous toe free flap.

PMID- 18087027
TI  - Docetaxel monotherapy for angiosarcoma in an elderly patient.

PMID- 18087028
TI  - A dermoscopy subpattern of plaque-type psoriasis: red globular rings.

PMID- 18087029
TI  - The role of the new "date rape drugs" in attributions about date rape.
AB  - This study investigates the effect of voluntary and involuntary drug use on
      attributions about sexual assault. The sample was composed of 280 randomly
      selected male and female undergraduate students. The type of drug used (GHB,
      alcohol, or none) and the voluntariness of the administration were varied in an
      unambiguous date rape scenario. Participants viewed sexual assault facilitated by
      alcohol or drugs similarly to sexual assault without drug or alcohol involvement,
      assigning the highest levels of responsibility and blame to the perpetrator and
      the lowest levels of both to the victim in these situations. In contrast, women's
      voluntary consumption of drugs prior to a sexual assault reduced perpetrator
      responsibility and blame and increased blame to the victim compared to other
      situations (except in some cases, voluntary drunkenness). These findings extend
      the limited research on date rape drugs and previous work on the influence of
      alcohol on date rape attributions.

PMID- 18087030
TI  - English- and Spanish-speaking women's use of violence.
AB  - This study analyzes variables related to the context and consequences of women's
      use of violence as well as a wide range of violent behaviors used and experienced
      by court-ordered English- and Spanish-speaking women. Data were derived from
      intake assessments of 125 court-ordered women over 24 months. Almost all of the
      women reported a history of abuse perpetrated by their partners. Women committed
      significantly fewer violent acts against their partners than their partners
      committed against them. Differences between English- and Spanish-speaking women's
      victimization, use of violence, and help seeking were largely similar, however,
      important differences emerged.

PMID- 18087031
TI  - Community response and needs of African American female survivors of domestic
      violence.
AB  - Relatively few studies have looked specifically at the experiences and needs of
      African American women who are survivors of domestic violence. This study sought
      to find out from African American survivors (a) what their experience was with
      various community entities and (b) how they feel race may have affected these
      experiences. Results indicate a great deal of dissatisfaction with the services
      received as they attempt to escape and/or stay away from their abusive partners.
      This dissatisfaction was in large measure due to lack of cultural competence.
      Implications for service and suggestions for community entities are presented.

PMID- 18087032
TI  - Experiences with dating aggression and sexual coercion among Polish college
      students.
AB  - Dating aggression and sexual coercion were studied in Polish college women (n =
      100) and men ( n = 101) using the Revised Conflict Tactics Scales (Straus, Hamby,
      Boney-McCoy, & Sugarman, 1996). Rates of psychological and physical aggression,
      sexual coercion, and injury were compared for men and women. Rates of physical
      aggression, sexual coercion, and injury were compared with preliminary data from
      31 universities and 16 countries from the International Dating Violence Study
      (IDVS; Straus, 2003, 2004). Rates of psychological aggression, physical
      aggression, and sexual coercion were high with respective rates of 77%, 36%, and
      42% for men and 89%, 48%, and 40% for women. Relative to the IDVS samples, Polish
      men and women had high levels of physical aggression and sexual coercion.
      Relative to the IDVS samples, women, but not men, had high levels of causing
      injury to their partner and using threats or actual physical force to obtain
      oral, anal, or vaginal intercourse. The possible influences of high levels of
      domestic violence in Polish society and rapid changes in women's roles are
      discussed.

PMID- 18087033
TI  - Classifying partner femicide.
AB  - The heterogeneity of domestic violent men has long been established. However,
      research has failed to examine this phenomenon among men committing the most
      severe form of domestic violence. This study aims to use a multidimensional
      approach to empirically construct a classification system of men who are
      incarcerated for the murder of their female partner based on the Holtzworth
      Munroe and Stuart (1994) typology. Ninety men who had been convicted and
      imprisoned for the murder of their female partner or spouse in England were
      identified from two prison samples. A content dictionary defining offense and
      offender characteristics associated with two dimensions of psychopathology and
      criminality was developed. These variables were extracted from institutional
      records via content analysis and analyzed for thematic structure using
      multidimensional scaling procedures. The resultant framework classified 80% (n =
      72) of the sample into three subgroups of men characterized by (a) low
      criminality/low psychopathology (15%), (b) moderate-high criminality/ high
      psychopathology (36%), and (c) high criminality/low-moderate psychopathology
      (49%). The latter two groups are akin to Holtzworth-Munroe and Stuart's (1994)
      generally violent/antisocial and dysphoric/borderline offender, respectively. The
      implications for intervention, developing consensus in research methodology
      across the field, and examining typologies of domestic violent men prospectively
      are discussed.

PMID- 18087034
TI  - Program completion in specialized batterer counseling for African-American men.
AB  - Despite the many recommendations for specialized counseling for African-American
      men arrested for domestic violence, research has yet to document its
      effectiveness in improving program completion. This experimental clinical trial
      compared the program completion rates of culturally-focused counseling in all
      African-American groups, conventional counseling in all-African-American groups,
      and conventional counseling in racially-mixed groups. The completion rate for the
      16-week program was approximately 55% across the three counseling options.
      Completion rates were slightly lower in the specialized counseling groups
      following stricter enforcement of dismissal policies. For men with high racial
      identification, the completion rate rose to between 63% and 65% in the culturally
      focused and conventional all-African-American groups versus only 40% in the
      racially-mixed groups. Programs might offer the option of culturally-focused
      counseling to African-American men to efficiently improve program completion. The
      influence of the program's strong link to the criminal justice system and weaker
      link to the community warrants further consideration.

PMID- 18087035
TI  - The elevated risk for non-lethal post-separation violence in Canada: a comparison
      of separated, divorced, and married women.
AB  - The purpose of the study was to shed light on the potentially differing dynamics
      of violence against separated and divorced women by their ex-husbands and
      violence against married women by their current husbands. Using a nationally
      representative sample of 7,369 heterosexual women from Cycle 13 of Statistics
      Canada's General Social Survey, available risk markers were examined in the
      context of a nested ecological framework. Separated women reported nine times the
      prevalence of violence and divorced women reported about four times the
      prevalence of violence compared with married women. The strongest predictors of
      violence against married women, namely, patriarchal domination, sexual jealousy,
      and possessiveness, were not significant predictors of violence against separated
      and divorced women. This suggested that post-separation violence is a complex
      phenomenon the dynamics of which can be affected by much more than domination and
      ownership.

PMID- 18087036
TI  - Community violence exposure of Southeast Asian American adolescents.
AB  - Southeast Asian adolescents in the United States face the daily challenge of
      adjusting to the American culture and their culture of origin. However, little is
      known about how the patterns of their bicultural adjustment influence
      psychological symptoms, especially when faced with other challenges such as
      community violence and negative life events. Additionally, the overrepresentation
      of Southeast Asian youth in the mental health and juvenile justice systems also
      necessitates a deeper understanding of the adjustment of this group of
      adolescents. Data from a sample of 80 Vietnamese and Cambodian adolescents who
      were between 13 and 18 years old revealed high rates of community violence
      witnessing and victimization, and a moderate level of negative life events. All
      of these stressors were related to higher externalizing and trauma-related
      symptoms, but only violence victimization and negative life events were related
      to higher internalizing symptoms. There was an additive effect of higher
      bicultural orientation related to lower externalizing and traumatic-stress
      symptoms in the face of stress and violence exposure, but no moderation effects
      were found.

PMID- 18087037
TI  - Staged in vitro reconstitution and implantation of engineered rat kidney tissue.
AB  - A major hurdle for current xenogenic-based and other approaches aimed at
      engineering kidney tissues is reproducing the complex three-dimensional structure
      of the kidney. Here, a stepwise, in vitro method of engineering rat kidney-like
      tissue capable of being implanted is described. Based on the fact that the stages
      of kidney development are separable into in vitro modules, an approach was
      devised that sequentially induces an epithelial tubule (the Wolffian duct) to
      undergo in vitro budding, followed by branching of a single isolated bud and its
      recombination with metanephric mesenchyme. Implantation of the recombined tissue
      results in apparent early vascularization. Thus, in principle, an unbranched
      epithelial tubular structure (potentially constructed from cultured cells) can be
      induced to form kidney tissue such that this in vitro engineered tissue is
      capable of being implanted in host rats and developing glomeruli with evidence of
      early vascularization. Optimization studies (of growth factor and matrix)
      indicate multiple suitable combinations and suggest both a most robust and a
      minimal system. A whole-genome microarray analysis suggested that recombined
      tissue recapitulated gene expression changes that occur in vivo during later
      stages of kidney development, and a functional assay demonstrated that the
      recombined tissue was capable of transport characteristic of the differentiating
      nephron. The approach includes several points where tissue can be propagated. The
      data also show how functional, 3D kidney tissue can assemble by means of
      interactions of independent modules separable in vitro, potentially facilitating
      systems-level analyses of kidney development.

PMID- 18087038
TI  - Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to
      increased cell proliferation and tumor risk.
AB  - Loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2),
      leading to abnormal activation of the normally silent maternal allele, is a
      common human epigenetic population variant associated with a 5-fold increased
      frequency of colorectal neoplasia. Here, we show first that LOI leads
      specifically to increased expression of proliferation-related genes in mouse
      intestinal crypts. Surprisingly, LOI(+) mice also have enhanced sensitivity to
      IGF-II signaling, not simply increased IGF-II levels, because in vivo blockade
      with NVP-AEW541, a specific inhibitor of the IGF-II signaling receptor, showed
      reduction of proliferation-related gene expression to levels half that seen in
      LOI(-) mice. Signal transduction assays in microfluidic chips confirmed this
      enhanced sensitivity with marked augmentation of Akt/PKB signaling in LOI(+)
      cells at low doses of IGF-II, which was reduced in the presence of the inhibitor
      to levels below those found in LOI(-) cells, and was associated with increased
      expression of the IGF1 and insulin receptor genes. We exploited this increased
      IGF-II sensitivity to develop an in vivo chemopreventive strategy using the
      azoxymethane (AOM) mutagenesis model. LOI(+) mice treated with AOM showed a 60%
      increase in premalignant aberrant crypt foci (ACF) formation over LOI(-) mice. In
      vivo IGF-II blockade with NVP-AEW541 abrogated this effect, reducing ACF to a
      level 30% lower even than found in exposed LOI(-) mice. Thus, LOI increases
      cancer risk in a counterintuitive way, by increasing the sensitivity of the IGF
      II signaling pathway itself, providing a previously undescribed epigenetic
      chemoprevention strategy in which cells with LOI are "IGF-II addicted" and
      undergo reduced tumorigenesis in the colon upon IGF-II pathway blockade.

PMID- 18087039
TI  - SUMOylation of pontin chromatin-remodeling complex reveals a signal integration
      code in prostate cancer cells.
AB  - Posttranslational modification by small ubiquitin-like modifier (SUMO) controls
      diverse cellular functions of transcription factors and coregulators and
      participates in various cellular processes including signal transduction and
      transcriptional regulation. Here, we report that pontin, a component of chromatin
      remodeling complexes, is SUMO-modified, and that SUMOylation of pontin is an
      active control mechanism for the transcriptional regulation of pontin on androgen
      receptor target genes in prostate cancer cells. Biochemical purification of
      pontin-containing complexes revealed the presence of the Ubc9 SUMO-conjugating
      enzyme that underlies its function as an activator. Intriguingly, 5alpha
      dihydroxytestosterone treatments significantly increased the SUMOylation of
      pontin, and SUMOylated pontin showed further activation of a subset of nuclear
      receptor-dependent transcription and led to an increase in proliferation and
      growth of prostate cancer cells. These data clearly define a functional model and
      provide a link between SUMO modification and prostate cancer progression.

PMID- 18087040
TI  - Regulation of p53 tetramerization and nuclear export by ARC.
AB  - Inactivation of the transcription factor p53 is central to carcinogenesis. Yet
      only approximately one-half of cancers have p53 loss-of-function mutations. Here,
      we demonstrate a mechanism for p53 inactivation by apoptosis repressor with
      caspase recruitment domain (ARC), a protein induced in multiple cancer cells. The
      direct binding in the nucleus of ARC to the p53 tetramerization domain inhibits
      p53 tetramerization. This exposes a nuclear export signal in p53, triggering Crm1
      dependent relocation of p53 to the cytoplasm. Knockdown of endogenous ARC in
      breast cancer cells results in spontaneous tetramerization of endogenous p53,
      accumulation of p53 in the nucleus, and activation of endogenous p53 target
      genes. In primary human breast cancers with nuclear ARC, p53 is almost always WT.
      Conversely, nearly all breast cancers with mutant p53 lack nuclear ARC. We
      conclude that nuclear ARC is induced in cancer cells and negatively regulates
      p53.

PMID- 18087041
TI  - Nanosecond electron tunneling between the hemes in cytochrome bo3.
AB  - Biological electron transfer (eT) between redox-active cofactors is thought to
      occur by quantum-mechanical tunneling. However, in many cases the observed rate
      is limited by other reactions coupled to eT, such as proton transfer,
      conformational changes, or catalytic chemistry at an active site. A prominent
      example of this phenomenon is the eT between the heme groups of mitochondrial
      cytochrome c oxidase, which has been reported to take place in several different
      time domains. The question of whether pure eT tunneling in the nanosecond regime
      between the heme groups can be observed has been the subject of some experimental
      controversy. Here, we report direct observations of eT between the heme groups of
      the quinol oxidase cytochrome bo(3) from Escherichia coli, where the reaction is
      initiated by photolysis of carbon monoxide from heme o(3). eT from CO-dissociated
      ferrous heme o(3) to the low-spin ferric heme b takes place at a rate of (1.2
      ns)(-1) at 20 degrees C as determined by optical spectroscopy. These results
      establish heme-heme electron tunneling in the bo(3) enzyme, a bacterial relative
      to the mitochondrial cytochrome c oxidase. The properties of eT between the
      closely lying heme groups in the heme-copper oxidases are discussed in terms of
      the reorganization energy for the process, and two methods for assessing the rate
      of electron tunneling are presented.

PMID- 18087042
TI  - Association of yeast Upf1p with direct substrates of the NMD pathway.
AB  - Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and
      degrades transcripts containing premature translation termination codons. Gene
      expression profiling experiments have shown that inactivation of the NMD pathway
      leads to the accumulation of both aberrant, nonsense-containing mRNAs, and many
      apparently wild-type transcripts. Such increases in transcript steady-state
      levels could arise from direct changes in the respective mRNA half-lives, or
      indirectly, as a consequence of the stabilization of transcripts encoding
      specific regulatory proteins. Here, we distinguished direct from indirect
      substrates by virtue of their association with the Saccharomyces cerevisiae Upf1
      protein. Analyses of this dataset, and its comparison to the sets of transcripts
      that respectively increase or decrease in abundance when NMD is either
      inactivated or reactivated, indicate that the number of direct NMD substrates is
      larger than previously thought and that low abundance, alternatively transcribed
      mRNAs, i.e., mRNAs whose 5' ends are derived from previously unannotated 5'
      flanking sequences, comprise a significant class of direct substrates. Using
      thiamine metabolism as an example, we also show that apparent NMD-regulated
      cellular pathways may actually reflect the detection of low-abundance alternative
      transcripts under conditions where a pathway is repressed.

PMID- 18087043
TI  - An extremes of outcome strategy provides evidence that multiple sclerosis
      severity is determined by alleles at the HLA-DRB1 locus.
AB  - Multiple sclerosis (MS) is a common inflammatory disease of the central nervous
      system unsurpassed for variability in disease outcome. A cohort of sporadic MS
      cases (n = 163), taken from opposite extremes of the distribution of long-term
      outcome, was used to determine the role of the HLA-DRB1 locus on MS disease
      severity. Genotyping sets of benign and malignant MS patients showed that HLA
      DRB1*01 was significantly underrepresented in malignant compared with benign
      cases. This allele appears to attenuate the progressive disability that
      characterizes MS in the long term. The observation was doubly replicated in (i)
      Sardinian benign and malignant patients and (ii) a cohort of affected sibling
      pairs discordant for HLA-DRB1*01. Among the latter, mean disability progression
      indices were significantly lower in those carrying the HLA-DRB1*01 allele
      compared with their disease-concordant siblings who did not. The findings were
      additionally supported by similar transmission distortion of HLA-DRB1*04 subtypes
      closely related to HLA-DRB1*01. The protective effect of HLA-DRB1*01 in sibling
      pairs may result from a specific epistatic interaction with the susceptibility
      allele HLA-DRB1*1501. A high-density (>700) SNP examination of the MHC region in
      the benign and malignant patients could not identify variants differing
      significantly between the two groups, suggesting that HLA-DRB1 may itself be the
      disease-modifying locus. We conclude that HLA-DRB1*01, previously implicated in
      disease resistance, acts as an independent modifier of disease progression. These
      results closely link susceptibility to long-term outcome in MS, suggesting that
      shared quantitative MHC-based mechanisms are common to both, emphasizing the
      central role of this region in pathogenesis.

PMID- 18087044
TI  - Recent acceleration of human adaptive evolution.
AB  - Genomic surveys in humans identify a large amount of recent positive selection.
      Using the 3.9-million HapMap SNP dataset, we found that selection has accelerated
      greatly during the last 40,000 years. We tested the null hypothesis that the
      observed age distribution of recent positively selected linkage blocks is
      consistent with a constant rate of adaptive substitution during human evolution.
      We show that a constant rate high enough to explain the number of recently
      selected variants would predict (i) site heterozygosity at least 10-fold lower
      than is observed in humans, (ii) a strong relationship of heterozygosity and
      local recombination rate, which is not observed in humans, (iii) an implausibly
      high number of adaptive substitutions between humans and chimpanzees, and (iv)
      nearly 100 times the observed number of high-frequency linkage disequilibrium
      blocks. Larger populations generate more new selected mutations, and we show the
      consistency of the observed data with the historical pattern of human population
      growth. We consider human demographic growth to be linked with past changes in
      human cultures and ecologies. Both processes have contributed to the
      extraordinarily rapid recent genetic evolution of our species.

PMID- 18087046
TI  - Evoked brain responses are generated by feedback loops.
AB  - Neuronal responses to stimuli, measured electrophysiologically, unfold over
      several hundred milliseconds. Typically, they show characteristic waveforms with
      early and late components. It is thought that early or exogenous components
      reflect a perturbation of neuronal dynamics by sensory input bottom-up
      processing. Conversely, later, endogenous components have been ascribed to
      recurrent dynamics among hierarchically disposed cortical processing levels, top
      down effects. Here, we show that evoked brain responses are generated by
      recurrent dynamics in cortical networks, and late components of event-related
      responses are mediated by backward connections. This evidence is furnished by
      dynamic causal modeling of mismatch responses, elicited in an oddball paradigm.
      We used the evidence for models with and without backward connections to assess
      their likelihood as a function of peristimulus time and show that backward
      connections are necessary to explain late components. Furthermore, we were able
      to quantify the contribution of backward connections to evoked responses and to
      source activity, again as a function of peristimulus time. These results link a
      generic feature of brain responses to changes in the sensorium and a key
      architectural component of functional anatomy; namely, backward connections are
      necessary for recurrent interactions among levels of cortical hierarchies. This
      is the theoretical cornerstone of most modern theories of perceptual inference
      and learning.

PMID- 18087045
TI  - Embryonic stromal clones reveal developmental regulators of definitive
      hematopoietic stem cells.
AB  - Hematopoietic stem cell (HSC) self-renewal and differentiation is regulated by
      cellular and molecular interactions with the surrounding microenvironment. During
      ontogeny, the aorta-gonad-mesonephros (AGM) region autonomously generates the
      first HSCs and serves as the first HSC-supportive microenvironment. Because the
      molecular identity of the AGM microenvironment is as yet unclear, we examined two
      closely related AGM stromal clones that differentially support HSCs. Expression
      analyses identified three putative HSC regulatory factors, beta-NGF (a
      neurotrophic factor), MIP-1gamma (a C-C chemokine family member) and Bmp4 (a TGF
      beta family member). We show here that these three factors, when added to AGM
      explant cultures, enhance the in vivo repopulating ability of AGM HSCs. The
      effects of Bmp4 on AGM HSCs were further studied because this factor acts at the
      mesodermal and primitive erythropoietic stages in the mouse embryo. In this
      report, we show that enriched E11 AGM HSCs express Bmp receptors and can be
      inhibited in their activity by gremlin, a Bmp antagonist. Moreover, our results
      reveal a focal point of Bmp4 expression in the mesenchyme underlying HSC
      containing aortic clusters at E11. We suggest that Bmp4 plays a relatively late
      role in the regulation of HSCs as they emerge in the midgestation AGM.

PMID- 18087047
TI  - Structural basis for the high all-trans-retinaldehyde reductase activity of the
      tumor marker AKR1B10.
AB  - AKR1B10 is a human aldo-keto reductase (AKR) found to be elevated in several
      cancer types and in precancerous lesions. In vitro, AKR1B10 exhibits a much
      higher retinaldehyde reductase activity than any other human AKR, including
      AKR1B1 (aldose reductase). We here demonstrate that AKR1B10 also acts as a
      retinaldehyde reductase in vivo. This activity may be relevant in controlling the
      first step of retinoic acid synthesis. Up-regulation of AKR1B10, resulting in
      retinoic acid depletion, may lead to cellular proliferation. Both in vitro and in
      vivo activities of AKR1B10 were inhibited by tolrestat, an AKR1B1 inhibitor
      developed for diabetes treatment. The crystal structure of the ternary complex
      AKR1B10-NADP(+)-tolrestat was determined at 1.25-A resolution. Molecular dynamics
      models of AKR1B10 and AKR1B1 with retinaldehyde isomers and site-directed
      mutagenesis show that subtle differences at the entrance of the retinoid-binding
      site, especially at position 125, are determinant for the all-trans-retinaldehyde
      specificity of AKR1B10. Substitutions in the retinaldehyde cyclohexene ring also
      influence the specificity. These structural features should facilitate the design
      of specific inhibitors, with potential use in cancer and diabetes treatments.

PMID- 18087048
TI  - Structure of the measles virus H glycoprotein sheds light on an efficient
      vaccine.

PMID- 18087049
TI  - Balancing efficacy and safety of drug-eluting stents in patients undergoing
      percutaneous coronary intervention.
AB  - Drug-eluting stents reduce the occurrence of in-stent restenosis and the need for
      subsequent target vessel revascularization compared with bare-metal stents.
      However, the safety of drug-eluting stents has been called into question because
      of an apparent increase in late stent thrombosis, a frequently fatal event. A
      substantial body of research has focused on determining the magnitude of these
      competing events, often reaching contradictory results even with analyses of the
      same data. Although larger, adequately powered, randomized trials are needed to
      fully assess the net clinical effects of drug-eluting stents compared with bare
      metal stents, the evidence seems to suggest that the net clinical benefit of drug
      eluting stents may outweigh their risks. The evidence is clearer that premature
      discontinuation of antiplatelet therapy is an important trigger for stent
      thrombosis; therefore, patients who are candidates for implantation of drug
      eluting stents should be screened for their ability to receive and tolerate
      uninterrupted antiplatelet therapy longer than is necessary with bare-metal
      stents. The evidence suggests that drug-eluting stents relieve obstructive
      coronary artery disease, provide durable mechanical results, and do more good
      than harm, but all patients also should be given antiplatelet and other optimal
      medical therapies to achieve the best outcomes.

PMID- 18087050
TI  - Systematic review: comparative effectiveness of treatments to prevent fractures
      in men and women with low bone density or osteoporosis.
AB  - BACKGROUND: Although several agents are available to treat osteoporosis, the
      relative efficacy and toxicity of these agents when used to prevent fractures has
      not been well described. PURPOSE: To compare the benefits in fracture reduction
      and the harms from adverse events of various therapies for osteoporosis. DATA
      SOURCES: MEDLINE (1966 to November 2007) and other selected databases were
      searched for English-language studies. STUDY SELECTION: For the efficacy
      analysis, investigators selected studies that reported the rate of or risk for
      fractures. For the adverse event analysis, they selected studies that reported
      the relationship between an agent and cardiovascular, thromboembolic, or upper
      gastrointestinal events; malignant conditions; and osteonecrosis. DATA
      EXTRACTION: Using a standardized protocol, investigators abstracted data on
      fractures and adverse events, agents and comparators, study design, and variables
      of methodological quality. DATA SYNTHESIS: Good evidence suggests that
      alendronate, etidronate, ibandronate, risedronate, zoledronic acid, estrogen,
      parathyroid hormone (1-34), and raloxifene prevent vertebral fractures more than
      placebo; the evidence for calcitonin was fair. Good evidence suggests that
      alendronate, risedronate, and estrogen prevent hip fractures more than placebo;
      the evidence for zoledronic acid was fair. The effects of vitamin D varied with
      dose, analogue, and study population for both vertebral and hip fractures.
      Raloxifene, estrogen, and estrogen-progestin increased the risk for
      thromboembolic events, and etidronate increased the risk for esophageal
      ulcerations and gastrointestinal perforations, ulcerations, and bleeding.
      LIMITATION: Few studies have directly compared different agents or classes of
      agents used to treat osteoporosis. CONCLUSION: Although good evidence suggests
      that many agents are effective in preventing osteoporotic fractures, the data are
      insufficient to determine the relative efficacy or safety of these agents.

PMID- 18087051
TI  - Summaries for patients. Screening for blockages in the blood vessels to the
      brain: recommendations from the U.S. Preventive Services Task Force.

PMID- 18087052
TI  - An externally validated model for predicting long-term survival after exercise
      treadmill testing in patients with suspected coronary artery disease and a normal
      electrocardiogram.
AB  - BACKGROUND: The exercise treadmill test is recommended for risk stratification
      among patients with intermediate to high pretest probability of coronary artery
      disease. Posttest risk stratification is based on the Duke treadmill score, which
      includes only functional capacity and measures of ischemia. OBJECTIVE: To develop
      and externally validate a post-treadmill test, multivariable mortality prediction
      rule for adults with suspected coronary artery disease and normal
      electrocardiograms. DESIGN: Prospective cohort study conducted from September
      1990 to May 2004. SETTING: Exercise treadmill laboratories in a major medical
      center (derivation set) and a separate HMO (validation set). PATIENTS: 33,268
      patients in the derivation set and 5821 in the validation set. All patients had
      normal electrocardiograms and were referred for evaluation of suspected coronary
      artery disease. MEASUREMENTS: The derivation set patients were followed for a
      median of 6.2 years. A nomogram-illustrated model was derived on the basis of
      variables easily obtained in the stress laboratory, including age; sex; history
      of smoking, hypertension, diabetes, or typical angina; and exercise findings of
      functional capacity, ST-segment changes, symptoms, heart rate recovery, and
      frequent ventricular ectopy in recovery. RESULTS: The derivation data set
      included 1619 deaths. Although both the Duke treadmill score and our nomogram
      illustrated model were significantly associated with death (P < 0.001), the
      nomogram was better at discrimination (concordance index for right-censored data,
      0.83 vs. 0.73) and calibration. We reclassified many patients with intermediate-
      to high-risk Duke treadmill scores as low risk on the basis of the nomogram. The
      model also predicted 3-year mortality rates well in the validation set: Based on
      an optimal cut-point for a negative predictive value of 0.97, derivation and
      validation rates were, respectively, 1.7% and 2.5% below the cut-point and 25%
      and 29% above the cut-point. LIMITATIONS: Blood test-based measures or left
      ventricular ejection fraction were not included. The nomogram can be applied only
      to patients with a normal electrocardiogram. Clinical utility remains to be
      tested. CONCLUSION: A simple nomogram based on easily obtained pretest and
      exercise test variables predicted all-cause mortality in adults with suspected
      coronary artery disease and normal electrocardiograms.

PMID- 18087053
TI  - Non-HACEK gram-negative bacillus endocarditis.
AB  - BACKGROUND: Infective endocarditis caused by non-HACEK (species other than
      Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium
      hominis, Eikenella corrodens, or Kingella species) gram-negative bacilli is rare,
      is poorly characterized, and is commonly considered to be primarily a disease of
      injection drug users. OBJECTIVE: To describe the clinical characteristics and
      outcomes of patients with non-HACEK gram-negative bacillus endocarditis in a
      large, international, contemporary cohort of patients. DESIGN: Observations from
      the International Collaboration on Infective Endocarditis Prospective Cohort
      Study (ICE-PCS) database. SETTING: 61 hospitals in 28 countries. PATIENTS:
      Hospitalized patients with definite endocarditis. MEASUREMENTS: Characteristics
      of non-HACEK gram-negative bacillus endocarditis cases were described and
      compared with those due to other pathogens. RESULTS: Among the 2761 case-patients
      with definite endocarditis enrolled in ICE-PCS, 49 (1.8%) had endocarditis (20
      native valve, 29 prosthetic valve or device) due to non-HACEK, gram-negative
      bacilli. Escherichia coli (14 patients [29%]) and Pseudomonas aeruginosa (11
      patients [22%]) were the most common pathogens. Most patients (57%) with non
      HACEK gram-negative bacillus endocarditis had health care-associated infection,
      whereas injection drug use was rare (4%). Implanted endovascular devices were
      frequently associated with non-HACEK gram-negative bacillus endocarditis compared
      with other causes of endocarditis (29% vs. 11%; P < 0.001). The in-hospital
      mortality rate of patients with endocarditis due to non-HACEK gram-negative
      bacilli was high (24%) despite high rates of cardiac surgery (51%). LIMITATIONS:
      Because of the small number of patients with non-HACEK gram-negative bacillus
      endocarditis in each treatment group and the lack of long-term follow-up, strong
      treatment recommendations are difficult to make. CONCLUSION: In this large,
      prospective, multinational cohort, more than one half of all cases of non-HACEK
      gram-negative bacillus endocarditis were associated with health care contact. Non
      HACEK gram-negative bacillus endocarditis is not primarily a disease of injection
      drug users.

PMID- 18087054
TI  - Brief communication: rituximab in HIV-associated multicentric Castleman disease.
AB  - BACKGROUND: HIV-associated multicentric Castleman disease is a rare
      lymphoproliferative disorder with marked systemic symptoms attributed to cytokine
      disarray. Many therapeutic approaches in small series of patients have proved
      largely unsuccessful to date. OBJECTIVE: To investigate the efficacy and
      clinicopathologic variables associated with first-line treatment for HIV
      associated multicentric Castleman disease with the anti-CD20 monoclonal antibody
      rituximab. DESIGN: Single-group, open-label, phase II trial. SETTING: 3 teaching
      hospitals in England. PATIENTS: Previously untreated patients with histologically
      proven HIV-associated multicentric Castleman disease. INTERVENTION: 4 infusions
      of rituximab, 375 mg per m2 of body surface area, at weekly intervals.
      MEASUREMENTS: Response was evaluated clinically and radiologically and by
      measuring plasma Kaposi sarcoma-associated herpesvirus viral load. RESULTS: 21
      consecutive patients (18 men) with plasmablastic multicentric Castleman disease
      were recruited. The median follow-up was 12 months (range, 1 to 49 months). One
      patient died before completing therapy, 20 achieved remission of symptoms, and 14
      (67%) achieved a radiologic response. The overall and disease-free survival rates
      at 2 years were 95% (95% CI, 86% to 100%) and 79% (CI, 49% to 100%),
      respectively. Plasma acute-phase proteins, immunoglobulins, and Kaposi sarcoma
      associated herpesvirus viral load decreased after rituximab therapy. The main
      adverse effect was reactivation of Kaposi sarcoma. LIMITATION: The study had no
      comparison group. CONCLUSION: Rituximab may be clinically valuable as initial
      therapy for HIV-associated multicentric Castleman disease.

PMID- 18087055
TI  - Meta-analysis: vitamin D compounds in chronic kidney disease.
AB  - BACKGROUND: Vitamin D compounds are widely used to prevent and treat secondary
      hyperparathyroidism. PURPOSE: To determine whether vitamin D therapy improves
      biochemical markers of mineral metabolism and cardiovascular and mortality
      outcomes in chronic kidney disease. DATA SOURCES: MEDLINE (January 1966 to July
      2007), EMBASE (January 1980 to July 2007), and Cochrane databases were searched
      without language restriction. STUDY SELECTION: Randomized, controlled trials of
      vitamin D compounds in chronic kidney disease were identified. DATA EXTRACTION:
      Two authors independently extracted data. DATA SYNTHESIS: Seventy-six trials were
      identified for inclusion; 3667 participants were enrolled. Vitamin D compounds
      did not reduce the risk for death, bone pain, vascular calcification, or
      parathyroidectomy. Compared with placebo, established vitamin D sterols were
      associated with an increased risk for hypercalcemia (relative risk, 2.37 [95% CI,
      1.16 to 4.85]) and hyperphosphatemia (relative risk, 1.77 [CI, 1.15 to 2.74]) but
      did not show a consistent reduction in parathyroid hormone (PTH) levels. Compared
      with placebo, more recently developed vitamin D analogues were associated with
      hypercalcemia (relative risk, 5.15 [CI, 1.06 to 24.97]) but not
      hyperphosphatemia, and levels of PTH were reduced (weighted mean difference, 
      10.77 pmol/L [CI, -20.51 to -1.03 pmol/L]). For suppression of PTH, intravenous
      administration was superior to oral vitamin D, but higher intravenous doses were
      used. LIMITATIONS: Few studies reported patient-level outcomes, including
      mortality (8 of 76 trials), and only 5 trials directly compared the effects of
      treatment with newer vitamin D compounds versus established ones. Heterogeneity
      in some comparisons remained unexplained by metaregression analyses. CONCLUSION:
      Vitamin D compounds do not consistently reduce PTH levels, and beneficial effects
      on patient-level outcomes are unproven. The value of vitamin D treatment for
      people with chronic kidney disease remains uncertain.

PMID- 18087056
TI  - Screening for carotid artery stenosis: U.S. Preventive Services Task Force
      recommendation statement.
AB  - DESCRIPTION: Update of the 1996 U.S. Preventive Services Task Force statement
      about screening for asymptomatic carotid artery stenosis (CAS) in the general
      population. METHODS: The U.S. Preventive Services Task Force examined the
      evidence on the natural history of CAS; systematic reviews of the accuracy of
      screening tests; observational studies of the harms of screening and treatment of
      asymptomatic CAS; and randomized, controlled trials of the benefits of treatment
      for CAS with carotid endarterectomy. RECOMMENDATION: Do not screen for
      asymptomatic CAS in the general adult population. (Grade D recommendation).

PMID- 18087057
TI  - Screening for carotid artery stenosis: an update of the evidence for the U.S.
      Preventive Services Task Force.
AB  - BACKGROUND: Cerebrovascular disease is the third leading cause of death in the
      United States. The proportion of all strokes attributable to previously
      asymptomatic carotid artery stenosis (CAS) is low. In 1996, the U.S. Preventive
      Services Task Force concluded that evidence was insufficient to recommend for or
      against screening of asymptomatic persons for CAS by using physical examination
      or carotid ultrasonography. PURPOSE: To examine the evidence of benefits and
      harms of screening asymptomatic patients with duplex ultrasonography and
      treatment with carotid endarterectomy for CAS. DATA SOURCES: MEDLINE and Cochrane
      Library (search dates January 1994 to April 2007), recent systematic reviews,
      reference lists of retrieved articles, and suggestions from experts. STUDY
      SELECTION: English-language randomized, controlled trials (RCTs) of screening for
      CAS; RCTs of carotid endarterectomy versus medical treatment; systematic reviews
      of screening tests; and observational studies of harms from carotid
      endarterectomy were selected to answer the following questions: Is there direct
      evidence that screening with ultrasonography for asymptomatic CAS reduces
      strokes? What is the accuracy of ultrasonography to detect CAS? Does intervention
      with carotid endarterectomy reduce morbidity or mortality? Does screening or
      carotid endarterectomy result in harm? DATA EXTRACTION: All studies were
      reviewed, abstracted, and rated for quality by using predefined Task Force
      criteria. DATA SYNTHESIS: No RCTs of screening for CAS have been done. According
      to systematic reviews, the sensitivity of ultrasonography is approximately 94%
      and the specificity is approximately 92%. Treatment of CAS in selected patients
      by selected surgeons could lead to an approximately 5-percentage point absolute
      reduction in strokes over 5 years. Thirty-day stroke and death rates from carotid
      endarterectomy vary from 2.7% to 4.7% in RCTs; higher rates have been reported in
      observational studies (up to 6.7%). LIMITATIONS: Evidence is inadequate to
      stratify people into categories of risk for clinically important CAS. The RCTs of
      carotid endarterectomy versus medical treatment were conducted in selected
      populations with selected surgeons. CONCLUSION: The actual stroke reduction from
      screening asymptomatic patients and treatment with carotid endarterectomy is
      unknown; the benefit is limited by a low overall prevalence of treatable disease
      in the general asymptomatic population and harms from treatment.

PMID- 18087058
TI  - Update on the methods of the U.S. Preventive Services Task Force: estimating
      certainty and magnitude of net benefit.
AB  - The major goal of the U.S. Preventive Services Task Force (USPSTF) is to provide
      a reliable and accurate source of evidence-based recommendations on a wide range
      of preventive services. In this article, the USPSTF updates and reviews the
      process by which it evaluates evidence, determines the certainty and magnitude of
      net benefit, and gives a final letter grade to recommendations. Because direct
      evidence about prevention is often unavailable, the Task Force usually considers
      indirect evidence. To guide its selection of indirect evidence, a "chain of
      evidence" is constructed within an analytic framework. The Task Force examines
      evidence of various research designs that addresses the key questions within the
      framework. New terms have been added to describe the USPSTF's judgment about the
      evidence for each key question: "convincing," "adequate," or "inadequate." For
      increased clarity, the USPSTF has changed its description of overall evidence of
      net benefit for the preventive service from "good," "fair," or "poor" quality to
      "high," "moderate," or "low" certainty. This rating considers the extent to which
      an uninterrupted chain of evidence exists across the analytic framework.
      Individual studies will continue to be judged as being of "good," "fair," or
      "poor" quality. Using outcomes tables, the USPSTF estimates the magnitude of
      benefits and the magnitude of harms, and synthesizes them into an estimate of the
      magnitude of net benefit. Although some judgment is required at all steps, the
      USPSTF strives to make the process as explicit and transparent as possible. The
      USPSTF anticipates that its methods for making evidence-based recommendations
      will continue to evolve.

PMID- 18087059
TI  - Caring for organs or for patients? Ethical concerns about the Uniform Anatomical
      Gift Act (2006).
AB  - In 2006, the National Conference of Commissioners on Uniform State Laws rewrote
      the Uniform Anatomical Gift Act. To overcome the problem of family members
      prohibiting organ donation from their deceased loved ones even when a donor card
      existed, the commissioners modified the act to prevent end-of-life care from
      precluding organ donation. An unintended consequence of the new wording creates
      the potential for end-of-life care that prioritizes care of the potential donor
      organs over care and comfort of the dying person. The commissioners have now
      revised the act, but the original version has already been legislated in many
      states, with others poised to follow. To protect dying patients' wishes about
      their end-of-life care, states that have legislated or are considering the
      original act must replace it with the revised version. A long-term and important
      ethical precept must stand: Care of dying patients takes precedence over organs.
      Another laudable goal must be promoted as well: Organ donation is an important
      part of end-of-life care.

PMID- 18087060
TI  - Vitamin D in patients with chronic kidney disease: nothing new under the sun.

PMID- 18087061
TI  - Tiotropium in combination with placebo, salmeterol, or fluticasone salmeterol for
      chronic obstructive pulmonary disease: possible confounding effect of treatment
      withdrawal?

PMID- 18087062
TI  - Estimating net benefits and harms of screening mammography in women age 40 to 49
      years.

PMID- 18087063
TI  - Chondroitin for osteoarthritis of the knee or hip.

PMID- 18087064
TI  - Chondroitin for osteoarthritis of the knee or hip.

PMID- 18087065
TI  - Chondroitin for osteoarthritis of the knee or hip.

PMID- 18087066
TI  - Very late restenosis after paclitaxel-eluting stent implantation.

PMID- 18087067
TI  - Toward an understanding of the molecular mechanism for successful blood feeding
      by coupling proteomics analysis with pharmacological testing of horsefly salivary
      glands.
AB  - Horseflies are economically important blood-feeding arthropods and also a
      nuisance for humans and vectors for filariasis. They rely heavily on the
      pharmacological properties of their saliva to get a blood meal and suppress
      immune reactions of hosts. Little information is available on antihemostatic
      substances in horsefly salivary glands; especially no horsefly immune
      suppressants have been reported. By proteomics or peptidomics and coupling
      transcriptome analysis with pharmacological testing, several families of proteins
      or peptides, which act mainly on the hemostatic system or immune system of the
      host, were identified and characterized from 30,000 pairs salivary glands of the
      horsefly Tabanus yao (Diptera, Tabanidae). They are: (i) a novel family of
      inhibitors of platelet aggregation including two members, which possibly inhibit
      platelet aggregation by a novel mechanism and act on platelet membrane, (ii) a
      novel family of immunosuppressant peptides including 12 members, which can
      inhibit interferon-gamma production and increase interleukin-10 secretion, (iii)
      a serine protease inhibitor with 56 amino acid residues containing anticoagulant
      activity, (iv) a serine protease with anticoagulant activity, (v) a protease with
      fibrinogenolytic activity, (vi) three families of antimicrobial peptides
      including six members, (vii) a hyaluronidase, (viii) a vasodilator peptide, which
      is an isoform of vasotab identified from Hybomitra bimaculata, and interestingly
      (ix) two metallothioneins, which are the first metallothioneins reported from
      invertebrate salivary glands. The current work will facilitate the understanding
      of the molecular mechanisms of the ectoparasite-host relationship and help in
      identifying novel vaccine targets and novel leading pharmacological compounds.

PMID- 18087068
TI  - Quantitative proteomics reveals regulation of dynamic components within TATA
      binding protein (TBP) transcription complexes.
AB  - Affinity purification in combination with isotope labeling of proteins has proven
      to be a powerful method to discriminate specific from nonspecific interactors.
      However, in the standard SILAC (stable isotope labeling by amino acids in cell
      culture) approach dynamic components may easily be assigned as nonspecific. We
      compared two affinity purification protocols, which in combination revealed
      information on the dynamics of protein complexes. We focused on the central
      component in eukaryotic transcription, the human TATA-binding protein, which is
      involved in different complexes. All known TATA-binding protein-associated
      factors (TAFs) were detected as specific interactors. Interestingly one of them,
      BTAF1, exchanged significantly in cell extracts during the affinity purification.
      The other TAFs did not display this behavior. Cell cycle synchronization showed
      that BTAF1 exchange was regulated during mitosis. The combination of the two
      affinity purification protocols allows a quantitative approach to identify
      transient components in any protein complex.

PMID- 18087069
TI  - Robust hit identification by quality assurance and multivariate data analysis of
      a high-content, cell-based assay.
AB  - Recent technological advances in high-content screening instrumentation have
      increased its ease of use and throughput, expanding the application of high
      content screening to the early stages of drug discovery. However, high-content
      screens produce complex data sets, presenting a challenge for both extraction and
      interpretation of meaningful information. This shifts the high-content screening
      process bottleneck from the experimental to the analytical stage. In this
      article, the authors discuss different approaches of data analysis, using a
      phenotypic neurite outgrowth screen as an example. Distance measurements and
      hierarchical clustering methods lead to a profound understanding of different
      high-content screening readouts. In addition, the authors introduce a hit
      selection procedure based on machine learning methods and demonstrate that this
      method increases the hit verification rate significantly (up to a factor of 5),
      compared to conventional hit selection based on single readouts only.

PMID- 18087070
TI  - Validation of a medium-throughput electrophysiological assay for KCNQ2/3 channel
      enhancers using IonWorks HT.
AB  - Enhancers of KCNQ channels are known to be effective in chronic pain models. To
      discover novel enhancers of KCNQ channels, the authors developed a medium
      throughput electrophysiological assay by using the IonWorks platform. Screening
      of 20 CHO-K1 clones stably expressing KCNQ2/3 was performed on the IonWorks HT
      until the best clone (judged from seal rate, current level, and stability) was
      obtained. The KCNQ2/3 current amplitude in the cells was found to increase from
      60 +/- 15 pA to 473 +/- 80 pA (at -10 mV), and the expression rate was increased
      by 56% when the cells were incubated at 27 degrees C overnight. The clone used
      for compound screening had a seal rate of greater than 90% and an overall success
      rate of greater than 70%. The voltage step protocol (hold cells at -80 mV and
      depolarize to -10 mV for 1 s) was designed to provide moderate current but still
      allow for pharmacological current enhancement. EC(50)s were generated from 8
      point concentration-response curves with a control compound on each plate using
      compounds that were also tested with conventional patch clamp. The authors found
      that there was a very good correlation (R(2) > 0.9) between the 2 assays, thus
      demonstrating the highly predictive nature of the IonWorks assay.

PMID- 18087071
TI  - Application of the BD ACTOne technology for the high-throughput screening of Gs
      coupled receptor antagonists.
AB  - A novel technology for monitoring the changes of 3,'5'-adenosine cyclic
      monophosphate (cAMP) in live cells suitable for drug screening relies on the use
      of cyclic nucleotide-gated channels as biosensors coexpressed with the
      appropriate target receptor. The technique (termed BD ACTOne) offers measurement
      of cAMP-dependent calcium influx or membrane depolarization with conventional
      fluorescent methods both in kinetic and in endpoint modes, optimal for high
      throughput and subsequent compound screening. The utility of the technique is
      reported here based on assay development and high-throughput screening for small
      molecule antagonists of the peptide parathyroid hormone 2 receptor (PTH2R). The
      dual-signaling properties of the receptor were retained in the recombinant
      system, and the observed pharmacological profile corresponded to data from
      radiolabeled cAMP determination. The membrane-potential-based high-throughput
      assay produced reproducible actives and led to the identification of several
      chemical scaffolds with potential utility as PTH2R ligands.

PMID- 18087072
TI  - A flow-through fluorescence polarization detection system for measuring GPCR
      mediated modulation of cAMP production.
AB  - A flow-through fluorescence polarization (FP) detection system that makes use of
      a novel high-performance liquid chromatography (HPLC) fluorescence detector
      modified with polarization filters was developed. This flow-through FP detection
      system was evaluated by using a novel and very cost-effective bioassay for cyclic
      adenosine monophosphate (cAMP). The bioassay was first evaluated and optimized in
      an FP plate reader format and subsequently in a flow-through bioassay setup. The
      principle of the bioassay is based on the competition of cAMP and a fluorescent
      cAMP derivative for the cAMP binding domain of protein kinase A. cAMP could
      accurately be determined over a range of 0.8 to 30 pmol/well in the plate reader
      FP assay and over a range of 0.3 to 50 pmol/well in the flow-through FP assay
      setup. High Z' factors (i.e., 0.89 for the plate reader and 0.93 for the flow
      through FP cAMP assay, respectively) indicated robust assays. Finally, functional
      cAMP signaling of the human histamine H(3) G-protein-coupled receptor (GPCR) in
      cell cultures was measured with both assay formats with good sensitivities and
      assay windows. The pEC(50) values obtained in both assay formats were in
      accordance with those obtained with standard methods. The flow-through FP
      detection system could thus be used as a cost-effective alternative to FP plate
      reader assays. Moreover, the novel flow-through FP detection system for cAMP
      constitutes a good analytical tool to be used in the GPCR research field as an
      alternative to the use of FP plate readers or radioactive laboratories nowadays
      used for cAMP measurements.

PMID- 18087073
TI  - Differential assay for high-throughput screening of antibacterial compounds.
AB  - The previously described Bacillus subtilis reporter strain BAU-102 is capable of
      detecting cell wall synthesis inhibitors that act at all stages of the cell wall
      synthesis pathway. In addition, this strain is capable of detecting compounds
      with hydrophobic/surfactant activity and alternative mechanisms of cell wall
      disruption. BAU-102 sequesters preformed beta-gal in the periplasm, suggesting
      leakage of beta-gal as the means by which this assay detects compound activities.
      A model is proposed according to which beta-gal release by BAU-102 reflects
      activation of pathways leading to autolysis. The authors also report a simplified
      high-throughput assay using BAU-102 combined with the fluorogenic substrate N
      methylumbelliferyl-beta-D-galactoside as a single reagent. Cell wall inhibitors
      release beta-gal consistently only after 60 min of incubation, whereas compounds
      with surfactant activity show an almost immediate release. A high-throughput
      screen of a 480-compound library of known bioactives yielded 8 compounds that
      cause beta-gal release. These results validate the BAU-102 assay as an effective
      tool in antimicrobial drug discovery.

PMID- 18087074
TI  - Growth, drug susceptibility, and gene expression profiling of Plasmodium
      falciparum cultured in medium supplemented with human serum or lipid-rich bovine
      serum albumin [corrected].
AB  - In vitro cultivation of Plasmodium falciparum has been extremely useful in
      understanding the biology of the human malaria parasite as well as research on
      the discovery of new antimalarial drugs and vaccines. A chemically defined serum
      free medium supplemented with lipid-rich bovine serum albumin (AlbuMAX I) offers
      the following advantages over human serum-supplemented media for the in vitro
      culture of P. falciparum: 1) improved growth profile, with more than a 2-fold
      higher yield of the parasites at any stage of the growth cycle; 2) suitability
      for in vitro antimalarial screening, as the parasites grown in AlbuMAX and human
      serum-supplemented media show similar sensitivity to standard and novel
      antimalarials as well as natural product extracts in the in vitro drug
      susceptibility assays; and 3) DNA microarray analysis comparing the global gene
      expression profile of sorbitol-synchronized P. falciparum trophozoites grown in
      the 2 different media, indicating minimal differences.

PMID- 18087077
TI  - The need for control of viral illnesses in India: a call for action.

PMID- 18087076
TI  - Poverty and blindness in Pakistan: results from the Pakistan national blindness
      and visual impairment survey.
AB  - OBJECTIVE: To explore the association between blindness and deprivation in a
      nationally representative sample of adults in Pakistan. DESIGN: Cross sectional
      population based survey. SETTING: 221 rural and urban clusters selected randomly
      throughout Pakistan. PARTICIPANTS: Nationally representative sample of 16 507
      adults aged 30 or above (95.3% response rate). MAIN OUTCOME MEASURES:
      Associations between visual impairment and poverty assessed by a cluster level
      deprivation index and a household level poverty indicator; prevalence and causes
      of blindness; measures of the rate of uptake and quality of eye care services.
      RESULTS: 561 blind participants (<3/60 in the better eye) were identified during
      the survey. Clusters in urban Sindh province were the most affluent, whereas
      rural areas in Balochistan were the poorest. The prevalence of blindness in
      adults living in affluent clusters was 2.2%, compared with 3.7% in medium
      clusters and 3.9% in poor clusters (P<0.001 for affluent v poor). The highest
      prevalence of blindness was found in rural Balochistan (5.2%). The prevalence of
      total blindness (bilateral no light perception) was more than three times higher
      in poor clusters than in affluent clusters (0.24% v 0.07%, P<0.001). The
      prevalences of blindness caused by cataract, glaucoma, and corneal opacity were
      lower in affluent clusters and households. Reflecting access to eye care
      services, cataract surgical coverage was higher in affluent clusters (80.6%) than
      in medium (76.8%) and poor areas (75.1%). Intraocular lens implantation rates
      were significantly lower in participants from poorer households. 10.2% of adults
      living in affluent clusters presented to the examination station wearing
      spectacles, compared with 6.7% in medium clusters and 4.4% in poor cluster areas.
      Spectacle coverage in affluent areas was more than double that in poor clusters
      (23.5% v 11.1%, P<0.001). CONCLUSION: Blindness is associated with poverty in
      Pakistan; lower access to eye care services was one contributory factor. To
      reduce blindness, strategies targeting poor people will be needed. These
      interventions may have an impact on deprivation in Pakistan.

PMID- 18087078
TI  - Immunobiology of human imunodeficiency virus infection.
AB  - After the discovery of human immunodeficiency virus (HIV) and its role in the
      causation of most devastating epidemic acquired immune deficiency syndrome
      (AIDS), there has been an increasing trend to decipher the mechanism of infection
      and to understand why it cannot be controlled by our immune system. By evolution,
      our immune system has been empowered and enough trained to recognize, elicit
      immune response and remove antigens and pathogens from the body. Simultaneously,
      HIV has also gained enough mechanism to escape the natural immune response. On
      one hand, it downregulates HLA class I antigens, which may present viral antigens
      to specific CD8 + T cells; on the other hand, the viral genome get mutated very
      readily under the selection pressure of specific cytotoxic T lymphocytes. The
      high mutation rate and convertibility of its genotype makes it a moving target
      and poses a prime hurdle in vaccine development. This review explains how HIV
      enters into the cell, how it resists the host immune response and how HIV manages
      to escape from it and establish in the human body.

PMID- 18087079
TI  - Serum levels of bcl-2 and cellular oxidative stress in patients with viral
      hepatitis.
AB  - PURPOSE: This study was conducted to investigate the presence of bcl-2 protein in
      the serum of patients with viral hepatitis and to find out if there is any
      correlation between bcl-2 protein levels and cellular oxidative stress in the
      pathogenesis of viral hepatitis. METHODS: This study was carried out on 130
      patients with viral hepatitis, 70 with chronic hepatitis, 30 with liver cirrhosis
      and 30 with hepatocellular carcinoma (HCC) in addition to 20 healthy persons as
      the control. Serum bcl-2 protein was estimated by enzyme-linked immunosorbent
      assay, serum malondialdehyde (MDA), nitric oxide (NO) and antioxidant enzymes
      (GSH, GSH-px, GR and SOD) were measured using spectrophotometric analysis.
      RESULTS: bcl-2 protein level was significantly elevated in the serum of HCC,
      cirrhosis and chronic hepatitis groups as compared to control group. There were
      significant positive correlations between higher bcl-2 protein level and viral
      hepatitis markers (HBsAg, anti-HCV antibodies) in HCC and cirrhotic patients as
      compared to chronic hepatitis group. An increase in oxidative stress markers
      (MDA, NO) and a decrease in antioxidant enzyme activities (SOD, GSH and GSH-px)
      were observed. However, there was a negative correlation between bcl-2 levels and
      GR in all studied patient groups. CONCLUSIONS: The release of oxidative free
      radicals, deficiency in antioxidant enzymes and the expression of bcl-2 protein
      might play a role in the pathogenesis of viral hepatitis. The ability to measure
      bcl-2 protein in the serum could be useful as a prognostic marker of cancer
      patients.

PMID- 18087080
TI  - Rapid identification of non-sporing anaerobes using nuclear magnetic resonance
      spectroscopy and an identification strategy.
AB  - PURPOSE: The non-sporing anaerobes cause a wide spectrum of infections. They are
      difficult to culture and their identification is tedious and time-consuming.
      Rapid identification of anaerobes is highly desirable. Towards this end, the
      potential of nuclear magnetic resonance (NMR) spectroscopy for providing a
      fingerprint within the proton spectrum of six genera belonging to anaerobes
      reflecting their characteristic metabolites has been investigated. METHODS: NMR
      analysis was carried out using Mercury plus Varian 300 MHz (7.05 T) NMR
      spectrophotometer on six different anaerobes. These included Bacteroides
      fragilis, Prevotella melaninogenica, Prevotella denticola, Fusobacterium
      necrophorum, Peptococcus niger and Peptostreptococcus spp. After the NMR analysis
      (256/512 scans), the different peaks were noted. The eight pus specimens, which
      yielded pure culture of anaerobe, also were analysed similarly. RESULTS: The
      major resonances of multiplex of amino acids/lipid at 0.9 ppm along with
      lactate/lipid at 1.3 ppm, acetate at 1.92 ppm and multiplex of lysine at 3.0 ppm
      remained constant to label the organism as an anaerobe. There was a difference
      found in the MR spectra of different genera and species. A simple algorithm was
      developed for the identification of the six different anaerobes studied. The MR
      spectra of the pure culture of the organism matched the MR spectra of pus from
      which the organism was isolated. CONCLUSIONS: MR-based identification was of
      value in the identification of anaerobes. However, a larger database of the peaks
      produced by anaerobes needs to be created for identification of all genera and
      species. It could then have the potential of diagnosing an anaerobic infection in
      vivo and thus expedite management of deep-seated abscesses.

PMID- 18087081
TI  - Species distribution and physiological characterization of Acinetobacter
      genospecies from healthy human skin of tribal population in India.
AB  - BACKGROUND: Various reports on distribution of Acinetobacter spp. from healthy
      human skin restricted to urban population. However, no such data is available
      from healthy human skin of tribal population not exposed to modern antibiotics
      during their life time. PURPOSE: Isolation, biotyping, distribution and
      physiological characterisation of Acinetobacter spp. from healthy human skin of
      tribal population. METHODS: Tribal population of Toranmal area of Satpuda Ranges,
      Maharashtra, India were sampled for ten body sites. Tentative Acinetobacter
      isolates were confirmed to the genus level by chromosomal DNA transformation
      assay and to species level using Bouvet and Grimont system. Novel physiological
      characteristics like pH, temperature and salt tolerance were studied. All strains
      were screened for production of various enzymes. RESULTS: One hundred and
      eighteen strains were isolated, which belonged to nine Acinetobacter genospecies.
      A. haemolyticus was most abundant followed by A. calcoaceticus and A. genospecies
      1-3. Higher percentage of Acinetobacter was recovered from skin of nose, Pawara
      tribe and female volunteers. They showed wide variation in temperature, salt and
      pH tolerance. Most of the strains could produce enzymes viz, lipase, esterase,
      urease and amylase. CONCLUSIONS: Acinetobacter spp. belonging to nine genospecies
      were obtained in the present study. Physiological characteristics including high
      salt, temperature and acidic pH tolerance were helpful to differentiate between
      the commensal and pathogenic species of Acinetobacter genus.

PMID- 18087082
TI  - Extended-spectrum beta-lactamases in ceftazidime-resistant Escherichia coli and
      Klebsiella pneumoniae isolates in Turkish hospitals.
AB  - PURPOSE: To study the prevalence of TEM-, SHV- and GES-type beta -lactamases
      among Escherichia coli and Klebsiella pneumoniae strains having ceftazidime MICs
      higher than 2 mg/L. METHODS: A total of 63 E. coli and 41 K. pneumoniae isolated
      from five different university hospitals were studied for the existence of TEM-,
      SHV- and GES-type beta -lactamases. Susceptibility tests were carried out
      according to the criteria of National Committee for Clinical Laboratory
      Standards. MICs were obtained by agar dilution method. Existence of extended
      spectrum beta -lactamases (ESBLs) were assessed by double-disc synergy test
      (DDST). Existence of the above-mentioned beta -lactamase genes were studied both
      by PCR with specific oligonucleotide primers and isoelectric focusing methods.
      RESULTS: None of the isolates were carbapenem-resistant. DDSTs were positive in
      50 (79.3%) and 33 (80.5%) of E. coli and K. pneumoniae , respectively. TEM gene
      was detected in 41 (65.1%) and 19 (46.3%), whereas SHV gene in 18 (28.6%) and 20
      (48.8%) of E. coli and K. pneumoniae strains, respectively. GES genes were not
      detected. CONCLUSIONS: TEM and SHV genes are highly prevalent among ESBL
      producing E. coli and K. pneumoniae , whereas GES-type ESBLs are absent and found
      not to be responsible of ceftazidime resistance in Turkish hospitals.

PMID- 18087083
TI  - Typhoid myopathy or typhoid hepatitis: a matter of debate.
AB  - PURPOSE: The aim of the present study was to evaluate the major source of
      increased serum enzyme level in typhoid fever and to determine the most relevant
      clinical entity, hepatitis or myopathy, during typhoid fever. METHODS: A total of
      118 subjects proved to have typhoid fever were evaluated for serum enzymes such
      as transaminases, alkaline phosphatase, lactate dehydrogenase (LDH) and
      creatinine kinase (CK); and their relation with each other, clinical symptoms and
      serum bilirubin were evaluated by regression methods. RESULTS: Hepatomegaly was
      revealed in 14% of the cases and was correlated with elevated serum biliribin
      (5.05 +/- 13.03 mg/dL in hepatomegalic subjects). Alanine aminotransferase (ALT)
      and CK were elevated in 22 and 60% of the cases, respectively. Correlation
      coefficient of CK with aspartate aminotransferase (AST) and LDH was R2 = 0.68 and
      0.75, respectively, which were higher than that of ALT with that two enzymes.
      CONCLUSIONS: In conclusion, elevation of serum enzymes in typhoid is mostly of
      muscular origin.

PMID- 18087084
TI  - Correlation between In vitro susceptibility and treatment outcome with
      azithromycin in gonorrhoea: a prospective study.
AB  - PURPOSE: This prospective study was carried out to determine the antimicrobial
      susceptibility of Neisseria gonorrhoeae isolates by disc diffusion method and
      minimum inhibitory concentration (MIC) by E -test with special reference to
      azithromycin. Also, the correlation between in vitro susceptibility and treatment
      outcome with single 2 g oral dose azithromycin was assessed. METHODS: The study
      included 75 gonococcal isolates from males with urethritis, females with
      endocervicitis and their sexual contacts. All isolates were subjected to
      susceptibility testing for penicillin, ciprofloxacin, tetracycline, ceftriaxone,
      spectinomycin, cefixime and azithromycin. Males with gonococcal urethritis were
      randomised to receive a single dose of either azithromycin or ceftriaxone. Forty
      two men with urethritis received 2 g single oral dose azithromycin, while all
      other patients were given 250 mg parentral ceftriaxone. All patients were called
      for follow-up to assess clinical and microbiological cure rates. RESULTS: While
      all the isolates were susceptible to ceftriaxone, spectinomycin, cefixime and
      azithromycin; 74 (98.7%), 24 (32%) and 23 (30.7%) strains were resistant to
      ciprofloxacin, penicillin and tetracycline respectively, by both disc diffusion
      method and E -test. The MIC range, MIC50 and MIC90 of N. gonorrhoeae strains, to
      azithromycin were 0.016-0.25, 0.064 and 0.19 microg/mL, respectively. Follow-up
      attendance of the patients was 52.4 with 100% clinical and microbiological cure
      rates. CONCLUSIONS: Results of our study indicate that 2 g single oral dose
      azithromycin is safe and effective in the treatment of uncomplicated gonorrhoea.

PMID- 18087085
TI  - Comparison of radiorespirometric Budemeyer assay with ATP assay and mouse foot
      pad test in detecting viable Mycobacterium leprae from clinical samples.
AB  - PURPOSE: This study compares the results of radiorespirometric Buddemeyer assay
      with adenosine triphosphate (ATP) assay and mouse foot pad (MFP) test to validate
      the sensitivity of Buddemeyer assay in detecting viable M. leprae in clinical
      samples. METHODS: Viability was assessed using all the three methods in 60 skin
      biopsy specimens, including 20 untreated lepromatous leprosy (BL-LL), 13 treated
      BL-LL, 12 untreated borderline tuberculoid to mid borderline (BT-BB) and 15
      treated BT-BB cases. RESULTS: Of the 20 untreated BL-LL cases tested, positivity
      indicating the presence of viable M. leprae was detected in 85, 60 and 85% with
      Buddemeyer, ATP and MFP test, respectively. Among the 13 treated BL-LL cases,
      scores were 61, 54 and 0%; among the 12 untreated BT-BB cases, the scores were
      58, 16 and 16% and among the 15 treated BT-BB cases, the scores were 46, 20, 0%,
      respectively. CONCLUSION: The detection sensitivity (positive scores) with three
      tests were closely comparable in the two untreated groups of cases. On the other
      hand, in the two treated groups, a good proportion of cases scored positive in
      the in vitro tests but none in the MFP test. Among the two in vitro methods, the
      Buddemeyer assay emerged as a better test, in terms of sensitivity and
      specificity.

PMID- 18087086
TI  - Detection of Mycoplasma species in cell culture by PCR and RFLP based method:
      effect of BM-cyclin to cure infections.
AB  - PURPOSE: A two-stage nested polymerase chain reaction (PCR) assay system was
      described that amplifies the 16S-23S rRNA spacer region sequences of Mycoplasma
      and Acholeplasma infections in cell cultures and virus stocks. METHODS:
      Established cell lines and virus stocks were screened for the presence of
      Mycoplasma by using nested PCR using two sets of outer and inner primers,
      amplifies 16S-23S rRNA. PCR and restriction fragment length polymorphism (RFLP)
      assay was used to detect and identify most of the species-specific Mycoplasmas
      involved in cell cultures and virus stock contaminants. Infected cultures
      detected by PCR-RFLP were further treated with BM-cyclin (5 microg/mL) and
      passaged for three times and tested for Mycoplasma infections by PCR-RFLP.
      RESULTS: Mycoplasma pirum and Mycoplasma orale infections were detected by nested
      PCR. Species specificity was identified by using RFLP of Vsp I, Cla I and Hin
      dIII restriction enzymes. Mycoplasma infections were cured by treatment with BM
      cyclin. This was further confirmed by non-amplification of PCR amplimers in BM
      cyclin treated vs. non-treated cultures. CONCLUSIONS: Regular monitoring of cell
      cultures for Mycoplasma infections and identification of species-specific
      Mollicutes will identify the source of contaminations. This approach can be used
      for quality control of the biological reagents used in cell culture and virology
      laboratories.

PMID- 18087087
TI  - Virulence factors and drug resistance in Escherichia coli isolated from
      extraintestinal infections.
AB  - PURPOSE: To determine the virulence factors produced by Escherichia coli isolated
      from extraintestinal infections, to study the drug resistance pattern in E. coli
      with special reference to extended spectrum beta -lactamase (ESBL) and to
      evaluate screening methods for ESBL. METHODS: A total of 152 isolates of E. coli
      from various extraintestinal infections were screened for virulence factors such
      as haemolysin, surface hydrophobicity, serum resistance and protease. All the
      isolates were also studied for antibiotic susceptibility pattern using modified
      Kirby Bauer disk diffusion method. ESBL production was screened by standard disk
      diffusion method and confirmed using phenotypic confirmatory method. RESULTS:
      Among 152 isolates, 36 (23.7%) were haemolytic, 42 (27.6%) were hydrophobic, 132
      (86.8%) were serum resistant and only four were positive for protease. Multiple
      virulence factor were observed in 67 (44%) of isolates. Seventy-nine (51.4%)
      isolates produced ESBL. ESBL producing isolates showed multidrug resistance.
      There was a significant association ( P E. coli . CONCLUSIONS: The present study
      shows the expression of virulence factors and multidrug resistance in E. coli
      isolated from various extraintestinal infections. The study also shows that
      appropriate methods of detecting drug resistance and ESBL production are required
      for the judicious use of antibiotics in managing these infections.

PMID- 18087088
TI  - Antimicrobial susceptibility testing of Helicobacter pylori to selected agents by
      agar dilution method in Shiraz-Iran.
AB  - PURPOSE: To assess the pattern of antimicrobial susceptibility profile of
      Helicobacter pylori isolates from patients with gastritis, duodenal ulcer (DU)
      and gastroesophageal reflux disease (GERD) residing in Shiraz, Iran. METHODS: One
      hundred and six H. pylori isolates from patients with gastritis, DU and GERD
      undergoing endoscopy at our university hospitals and clinics were analysed for
      their antimicrobial susceptibility to metronidazole, clarithromycin, amoxicillin,
      co-amoxiclav, tetracycline, ciprofloxacin and furazolidone. The minimum
      inhibitory concentrations were determined by agar dilution method. RESULTS:
      Overall H. pylori resistance rate was 72.6% to metronidazole, 9.4% to
      clarithromycin and furazolidone, 20.8% to amoxicillin and 4.7% to tetracycline
      and ciprofloxacin. No resistance to co-amoxiclav was detected among H. pylori
      isolates. No significant differences between antimicrobial resistance and
      clinical outcome were detected. CONCLUSIONS: With regard to the increasing
      resistance of H. pylori isolates to various antibiotics, susceptibility testing
      of H. pylori isolates prior to the treatment of infection must be performed to
      achieve better eradication and to reduce the risk of selection of H. pylori
      resistant strains.

PMID- 18087089
TI  - Outbreak of acute viral hepatitis due to hepatitis E virus in Hyderabad.
AB  - PURPOSE: A waterborne outbreak of viral hepatitis occurred in the old city of
      Hyderabad from March through August 2005. An attempt was made to study the
      outbreak clinically, serologically, and etiologically. METHODS: Five hundred and
      forty-six clinically and biochemically documented cases were screened for the
      hepatotropic viral markers, hepatitis A, B, C, and E by the ELISA method. Their
      demographic characteristics and outcomes were analyzed. Point source
      contamination of the water supply with sewerage was identified. RESULT: Our data
      confirms hepatitis E as the major cause of the outbreak (78.57%). Occasionally,
      mixed infection of HEV-HAV (5.31%) or HEV-HBV (0.91%) was detected in the present
      series of acute viral hepatitis. CONCLUSIONS: HEV was confirmed as the major
      etiological agent in this outbreak that was transmitted by contaminated drinking
      water. The study highlights the importance of screening for both enterically
      transmitted hepatotropic viral markers as well as the parenterally transmitted
      hepatotropic viral markers during outbreaks of acute viral hepatitis.

PMID- 18087090
TI  - A comparative study for the detection of Mycobacteria by BACTEC MGIT 960,
      Lowenstein Jensen media and direct AFB smear examination.
AB  - PURPOSE: To compare BACTEC MGIT 960 (M960) with conventional culture on
      Lowenstein Jensen (LJ) media and direct acid fast bacilli (AFB) smear examination
      for the detection of Mycobacteria in clinical samples obtained from suspected
      cases of pulmonary and extra pulmonary tuberculosis (TB). METHODS: A total of 500
      samples were processed for direct AFB smear examination, and culture on M960 and
      LJ media. RESULTS: Two hundred fifty-eight out of 500 (51.6%) isolates of
      Mycobacteria were obtained by combined use of the two culture methods. Two
      hundred and fifty-three (50.6%) were positive in culture by M960 and LJ media and
      28% (140/500) by direct AFB smear examination. The positivity rate of M960 system
      alone was 34.10% (88/258) and of LJ alone was 1.93% (5/258). Average time to
      detect growth (TTD) was 9.66 days by M960 and 28.81 days by LJ. CONCLUSIONS: M960
      system is a rapid and sensitive method for early diagnosis of pulmonary and
      extrapulmonary TB. But for maximum recovery of Mycobacteria , a combination of
      both M960 and LJ media should be used.

PMID- 18087091
TI  - Cytokine levels in patients with brucellosis and their relations with the
      treatment.
AB  - PURPOSE: To determine the serum levels of proinflammatory and some of the Th1/Th2
      cytokines in brucellosis and their alterations with treatment and outcome.
      METHODS: Twenty-eight acute and seven subacute brucellosis patients diagnosed
      clinically were included in the study. Twenty healthy volunteers were also
      included. Brucella standard tube agglutination tests and blood culture were
      conducted on all subjects. Cytokine levels of pre- and post-treatment period
      serum samples were measured by ELISA. RESULTS: The mean serum levels of IL-6, IFN
      gamma and TNF-alpha were significantly higher in brucellosis patients compared to
      the control group ( P < 0.05). No significant differences were found between
      patient and control groups in terms of IL-1beta , TGF-beta 1, IL-2, IL-4 and IL-8
      levels. There was a positive correlation between IFN-gamma, TNF-alpha and IL-6
      levels with CRP levels. IL-6, IFN-gamma and TNF-alpha levels measured after
      treatment were statistically significantly lower than pre-treatment values ( P <
      0.001). No differences were found in the levels of these cytokines between acute
      and subacute patients' sera. IL-6, IFN-gamma and TNF-alpha levels were higher in
      acute or subacute brucellosis patients. CONCLUSIONS: Although the levels of the
      cytokines were decreased significantly with effective and adequate treatment
      these alterations did not correlate with the extent or activity of the disease.

PMID- 18087092
TI  - Rapid detection of non-enterobacteriaceae directly from positive blood culture
      using fluorescent in situ hybridization.
AB  - Fluorescent in situ hybridization (FISH) was carried out using two different
      oligonucleotide probes specific for Pseudomonas spp. and Acinetobacter spp. These
      probes were tested against different organisms and were found to be highly
      specific. Sensitivity testing showed that the probes were able to detect as low
      as 10 3 CFU/mL. In addition, FISH was carried out directly on positive blood
      culture samples and the detection of microorganisms took less than 2 h. We
      believe that FISH is a rapid method that can be used as a routine laboratory
      diagnostic technique for the detection of Acinetobacter spp. and Pseudomonas spp.
      in clinical samples.

PMID- 18087093
TI  - Latex particle agglutination test as an adjunct to the diagnosis of bacterial
      meningitis.
AB  - The present study aimed to review the results of microscopic examination, routine
      culture and antigen detection by latex particle agglutination test (LPAT), in
      order to evaluate the diagnostic value of the LPAT in establishing the
      aetiological diagnosis of bacterial meningitis. LPAT was done in 65 clinically
      suspected meningitis cases ranging from 5 days to 60 years of age and was
      compared with culture and Gram stain. Using LPAT, an aetiological diagnosis could
      be done in 10 out of 65 (15.4%) cases of bacterial meningitis. In contrast, Gram
      stain and culture showed 16.9 and 23.1% positivity, respectively. LPAT correlated
      well with Gram stain and culture and can be recommended as an adjunct laboratory
      test for rapid aetiological diagnosis of bacterial meningitis for prompt
      institution of proper antibiotics.

PMID- 18087094
TI  - Helminthic infestation in children of Kupwara district: a prospective study.
AB  - The present study deals with the investigation of the frequency of intestinal
      helminth parasites in children of Kupwara, Kashmir, India. Three hundred and
      twelve children in the age group of 4-15 years were examined for different
      intestinal helminths in three schools located in rural areas. Two hundred and
      twenty two of 312 (71.15%) tested positive for various intestinal helminths. The
      various helminth parasites included Ascaris lumbricoides , Trichuris trichiura ,
      Enterobius vermicularis and Taenia saginata . By far, the highest frequency of
      69.23% (216/312) was noted for Ascaris lumbricoides followed by Trichuris
      trichiura 30.76% (96/312), Enterobius vermicularis 7.69% (24/312) and Taenia
      saginata 7.69% (24/312). Single infection was found in 33.65% (105/312) and mixed
      infection was seen in 37.5% (117/312) children. This study emphasizes the need
      for improved environmental conditions, i.e., clean water supplies, enhanced
      sanitation and chemotherapy of school-age children in rural areas.

PMID- 18087095
TI  - Clinical and mycological profile of cryptococcosis in a tertiary care hospital.
AB  - This study examined the extent of cryptococcosis in clinically diagnosed cases of
      meningitis in HIV-1 seropositive and apparently immunocompetent patients. One
      hundred and forty-six samples, obtained from 126 chronic meningitis patients
      comprised of cerebrospinal fluid (CSF), blood, sputum and urine. The samples were
      processed by standard microbiological procedures. Cryptococcal isolates were
      identified by microscopy, cultural characteristics, melanin production on niger
      seed agar and hydrolysis of urea. The isolates were further speciated on
      cannavanine glycine bromothymol blue (CGB) media. Cryptococcal antigen detection
      of CSF samples was performed by latex agglutination test (LAT). Minimum
      inhibitory concentration (MIC) of amphotericin B for the isolates was also
      tested. Cryptococcosis was diagnosed in 13 patients (eight HIV-1 seropositive and
      five apparently immunocompetent). Cryptococcus neoformans var. neoformans was the
      predominant isolate. Cryptococcal antigen was detected in all, whereas microscopy
      could detect yeast cells in nine patients. The isolates were sensitive to
      amphotericin B. CD4 cell counts ranged from 8 to 96/cu mm. The study concludes
      that all CSF samples with clinical diagnosis of subacute and chronic meningitis
      should be subjected to tests for detection of Cryptococcus in clinical laboratory
      irrespective of the immune status.

PMID- 18087096
TI  - Candida spp. other than Candida albicans: a major cause of fungaemia in a
      tertiary care centre.
AB  - This study was conducted to determine the frequency of different Candida spp.
      isolated from different parts of the hospital, associated risk factors and
      mortality rate. A total of 59 cases were selected for prospective analysis over a
      period of one and half years. Blood samples collected were processed by BACTEC
      (9240) method. Candidaemia was diagnosed by positive blood culture at least from
      two blood culture samples or from a clinically significant single blood culture
      sample. Candida spp. were identified by standard techniques. Most frequent
      isolates were C. tropicalis (35.6%), C. parapsilosis (28.8%), C. glabrata (11.9%)
      and C. pelliculosa (11.9%). Candida albicans was isolated only in 3.4% cases.
      Neonatology department accounted for highest number of isolates (27.1%), followed
      by gastrointestinal surgery (15.3%) and cardiac surgery (13.6%). Mortality was
      noted in 16.9%. Probable risk factors determined were intensive care unit stay
      (74.6%), antibiotic therapy (50.8%), central line (42.4%), urinary catheter
      (32.2%), ventilator (23.7%), malignancy (20.3%) and abdominal surgery (15.3%).

PMID- 18087098
TI  - Ocular toxocariasis in a child: a case report from Kashmir, north India.
AB  - Toxocariasis is an important zoonotic disease caused by the second stage larva of
      Toxocara canis or Toxocara cati . The typical clinical syndromes of toxocariasis
      in humans are visceral and ocular toxocariasis. Ocular toxocariasis may presents
      as peripheral inflammatory mass, posterior pole granuloma and endophthalmitis. We
      report a serologically confirmed case of ocular toxocariasis in 12-year-old
      female. The diagnosis was confirmed by detection of anti- Toxocara antibodies in
      aqueous and vitreous sample by enzyme-linked immunosorbent assay. We suggest that
      ophthalmologist in this region should include ocular toxocariasis in differential
      diagnosis particularly in children and young adults.

PMID- 18087097
TI  - Enterobacter sakazakii in infants: novel phenomenon in India.
AB  - E. sakazakii has been implicated in necrotizing enterocolitis, bloodstream and
      central nervous system infections, with mortality rates of 40-80%. Two cases of
      E. sakazakii infections; one preterm very low birth weight neonate with
      meningitis and a two month infant with bacteraemia, are described for the first
      time in India. The first baby succumbed to the infection while the other
      responded to appropriate therapy. Powdered infant milk formulae have been
      implicated in causing neonatal infections and the first baby was on formula feed
      with classic signs of sepsis and meningitis. The second infant was on breast feed
      and probably developed nosocomial E. sakazakii bacteraemia.

PMID- 18087099
TI  - Cutaneous actinomycosis: a rare case.
AB  - Cutaneous actinomycosis is a rare presentation. Here we present a case of
      cutaneous actinomycosis with no history of trauma or systemic dissemination. The
      isolate was identified as Actinomyces viscosus by standard methods. The isolate
      was found to be penicillin resistant by Kirby Bauer disc diffusion method.
      Therefore, the patient was treated with cotrimoxazole and improved. Thus, this
      case highlights the importance of isolation and susceptibility testing in
      actinomycotic infection. The sinuses have healed, and the patient has recovered.

PMID- 18087100
TI  - Fatal haemophagocytic syndrome and hepatitis associated with visceral
      leishmaniasis.
AB  - Haemophagocytic syndrome (HPS) secondary to infections occurs due to excessive,
      non-malignant proliferation of histiocytes, with resultant haemophagocytosis. The
      syndrome is essentially treatable, provided timely etiological diagnosis is
      achieved. In this report, we present a rare case of a child who hailed from
      Uttaranchal and presented with severe hepatitis. Bone marrow examination revealed
      an unexpected diagnosis of HPS secondary to visceral leishmaniasis. Despite
      initiating appropriate antileishmanial treatment, the child had a fatal outcome.

PMID- 18087101
TI  - A rare case of mucormycosis of median sternotomy wound caused by Rhizopus
      arrhizus.
AB  - We describe a case of mucormycosis of median sternotomy wound caused by Rhizopus
      arrhizus . The patient, a known diabetic and a case of coronary artery disease
      underwent coronary artery bypass surgery. In the postoperative period, patient
      developed infection of the median sternotomy wound, from which R. arrhizus was
      isolated on culture. Patient succumbed in spite of being treated with surgical
      debridement and amphotericin B. To the best of our knowledge, this is the first
      reported case of mucormycosis of median sternotomy wound from India.

PMID- 18087102
TI  - Mycobacterium fortuitum keratitis.
AB  - We report a case of mycobacterial keratitis characterized by apparently
      spontaneous onset, delayed diagnosis, and eventually necessitating evisceration
      inspite of systemic antibiotics and repeated corneal grafts.

PMID- 18087103
TI  - Prevention of parent-to-child transmission of HIV: an experience in rural
      population.

PMID- 18087104
TI  - Combining vital staining with fast plaque: TB assay.

PMID- 18087105
TI  - Disseminated histoplasmosis - comment 2.

PMID- 18087106
TI  - Disseminated histoplasmosis - comment 1.

PMID- 18087107
TI  - Microwave disinfection of gauze contaminated with bacteria and fungi.

PMID- 18087108
TI  - Endoscope reprocessing: stand up and take notice!

PMID- 18087109
TI  - Prevalence of Toxoplasma gondii infection amongst pregnant women in Assam, India.

PMID- 18087110
TI  - Evaluation of glucose-methylene-blue-mueller-hinton agar for E-test minimum
      inhibitory concentration determination in Candida spp.

PMID- 18087111
TI  - Resurgence of diphtheria in the vaccination era.

PMID- 18087112
TI  - A report of Pseudomonas aeruginosa antibiotic resistance from a multicenter study
      in Iran.

PMID- 18087113
TI  - Trends of antibiotic resistance in Salmonella enterica serovar typhi isolated
      from hospitalized patients from 1997 to 2004 in Lagos, Nigeria.

PMID- 18087114
TI  - Effects of binaural electronic hearing protectors on localization and response
      time to sounds in the horizontal plane.
AB  - The effects of electronic hearing protector devices (HPDs) on localization and
      response time (RT) to stimuli were assessed at six locations in the horizontal
      plane. The stimuli included a firearm loading, telephone ringing and .5-kHz and 4
      kHz tonebursts presented during continuous traffic noise. Eight normally hearing
      adult listeners were evaluated under two conditions: (a) ears unoccluded; (b)
      ears occluded with one of three amplitude-sensitive sound transmission HPDs. All
      HPDs were found to affect localization, and performance was dependent on stimuli
      and location. Response time (RT) was less in the unoccluded condition than for
      any of the HPD conditions for the broadband stimuli. In the HPD conditions, RT to
      incorrect responses was significantly less than RT to correct responses for 120
      degrees and 240 degrees , the two locations with the greatest number of errors.
      The RTs to incorrect responses were significantly greater than to correct
      responses for 60 degrees and 300 degrees , the two locations with the least
      number of errors. The HPDs assessed in this study did not preserve localization
      ability under most stimulus conditions.

PMID- 18087115
TI  - Factorial validity of the noise sensitivity questionnaire.
AB  - The Noise Sensitivity Questionnaire (NoiSeQ) aims at the measurement of global
      noise sensitivity as well as the sensitivity for five domains of everyday life
      namely 'Leisure', 'Work', 'Habitation', 'Communication' and 'Sleep'. The present
      investigation examined the factorial validity of the NoiSeQ to determine whether
      the items of the NoiSeQ cover the different factors as assumed. The analysis was
      done using the method of Confirmatory Factor Analysis (CFA). The linear
      structural model took into consideration only the scales of the NoiSeQ for which
      reliability could be demonstrated, namely, 'Sleep', 'Communication', 'Habitation'
      and 'Work'. The linear structural model presumed that each of the 28 items has a
      relation only to one corresponding factor. Furthermore, the model allowed for
      correlations between the four factors. The data base encompassed 293 persons.
      Parameter estimation was based on the General Least Square method. The data was
      checked with respect to the occurrence of multivariate outliers, deviation from
      multivariate normality and existing collinearities. The data met the overall
      requirements of a CFA. The evaluation of model fit was based on the relative chi2
      -value, the Root Mean Square Error of Approximation, the Goodness of Fit Index,
      the Adjusted Goodness of Fit Index and the Root Mean Square Residual. All fit
      indices indicated an acceptable match of the model. As the postulated structure
      of the NoiSeQ was consistent with the empirical data, the classification of the
      items as well as the claimed interdependencies between the scales can be
      maintained. The regression weights of all items as well as the correlations
      between the latent variables were statistically significant. The estimated
      reliability of the latent variables took values of >/=0.84. The findings
      generally justified the conclusion that there is no urgent need to modify the
      four scales of the NoiSeQ thus, indicating the factorial validity of the NoiSeQ.

PMID- 18087116
TI  - Sound localization with communications headsets: comparison of passive and active
      systems.
AB  - Studies have demonstrated that conventional hearing protectors interfere with
      sound localization. This research examines possible benefits from advanced
      communications devices. Horizontal plane sound localization was compared in
      normal-hearing males with the ears unoccluded and fitted with Peltor H10A passive
      attenuation earmuffs, Racal Slimgard II communications muffs in active noise
      reduction (ANR) and talk-through-circuitry (TTC) modes and Nacre QUIETPRO TM
      communications earplugs in off (passive attenuation) and push-to-talk (PTT)
      modes. Localization was assessed using an array of eight loudspeakers, two in
      each spatial quadrant. The stimulus was 75 dB SPL, 300-ms broadband noise. One
      block of 120 forced-choice loudspeaker identification trials was presented in
      each condition. Subjects responded using a laptop response box with a set of
      eight microswitches in the same configuration as the speaker array. A repeated
      measures ANOVA was applied to the dataset. The results reveal that the overall
      percent correct response was highest in the unoccluded condition (94%). A
      significant reduction of 24% was observed for the communications devices in TTC
      and PTT modes and a reduction of 49% for the passive muff and plug and muff with
      ANR. Disruption in performance was due to an increase in front-back reversal
      errors for mirror image spatial positions. The results support the conclusion
      that communications devices with advanced technologies are less detrimental to
      directional hearing than conventional, passive, limited amplification and ANR
      devices.

PMID- 18087117
TI  - Modulation of renal inflammation: therapeutic strategies.
AB  - Inflammation is a complex process that reflects the local and systemic responses
      to different immunological and non-immunological stimuli, enable resistance to
      disease, repair of tissue damage, and restoration of normal function with the
      least possible tissue damage. This is achieved by intact regulatory immune
      system, which includes pro- and anti-inflammatory cytokines, chemokines, growth
      factors, complement cascade system, renin-angiotensin system, and different sets
      of adhesion molecules expressed on leukocytes and vascular endothelium, in
      addition to neutrophils, monocytes/macrophages, and different subsets of T
      lymphocytes. Once imbalance occurs in the different factors of the inflammatory
      response to injurious stimuli, inflammation will proceed and exacerbate tissue
      damage. Inflammation can be initiated by different stimuli such as deposition or
      formation of antibody-antigen immune complexes, sensitized T-cells, trauma,
      tissue necrosis, or infection. It is characterized by activation of acute phase
      response and release of reactants/markers such as C-reactive protein. Renal
      inflammation can occur either as an isolated local acute inflammatory reaction or
      as part of a systemic inflammatory disorder. Recently, there have been tremendous
      advancements in the fields of immunology and molecular biology that helped in
      exploring the mechanisms of renal inflammation. This has been accompanied by
      extensive in vitro and in vivo studies that led to a better understanding of
      phenotypic changes and multifunctional potentials of local and infiltrating
      cells, role and control of different inflammatory mediators, adhesion molecules,
      and the rennin-angiotensin system within the site of inflammation. These
      achievements helped in researching into ways to modulate renal inflammation,
      control the severity of renal injury, promote regeneration and tissue repair, and
      induce tolerance.

PMID- 18087118
TI  - Which is the best way of performing a Micturating Cystourethrogram in children?
AB  - The Micturating Cystourethrogram (MCU) is a tough and stressful examination for
      patients and their parents as well as the radiologists and pediatric radiology
      nurses. Even though, it is one of the most commonly used fluoroscopic procedures
      in pediatric radiology practice, there is no definite agreement as to the best
      way to perform it, considering that this examination results in the children
      receiving a high dose of radiation to the gonadal region. This review was
      undertaken to determine the best way to perform the MCU in modern pediatric
      radiology practice.

PMID- 18087119
TI  - Evaluation of blood flow in allograft renal arteries anastomosed with two
      different techniques.
AB  - Renal artery stenosis in renal transplantation (TRAS) is an avoidable short or
      long-term surgical complication. The etiology is multifactorial, but faulty
      anastomosis is a major factor. In our transplant center, we evaluated the
      incidence of TRAS with the use of two different suturing techniques of the
      anastomosis site between the allograft renal and iliac arteries in two groups of
      renal transplant recipients, group A: 14 patients (6 males and 8 females with age
      16 to 59 and mean age of 38 years) in whom the allograft arteries were
      anastomosed with a continuous suture technique, and group B: 14 patients (7 males
      and 7 females, with age 32 to 61 and mean age of 46.6 years) in whom the
      allograft arteries were anastomosed with a combined suture technique (continuous
      and interrupted). Post transplantation, the velocity of blood flow in the renal
      and iliac arteries at the site of anastomosis was measured by color Doppler
      ultrasound. The ultrasonographer was blinded to the surgical technique in both
      study groups. The ratio of the maximum velocity of blood at the site of
      anastomosis to that in the iliac artery of less than 2.5 was considered as non
      significant stenosis, while a ratio of more than 2.5 was considered significant
      stenosis. In group A there were 9 cases of non-significant stenosis in comparison
      to 3 cases in group B, while there were no cases of significant stenosis in group
      A in comparison to 3 cases in group B; the difference was not statistically
      significant. We conclude that there was no difference in the incidence of
      stenosis in the compared surgical techniques of anastomosis in our study groups.
      This suggests that other factors such as gentle handling of tissue, enough
      spatula, margin reversion, and comparable diameter of the anastomosed vessels may
      be more important in the prevention of renal allograft stenosis than the type of
      suture technique.

PMID- 18087120
TI  - Correlation of clinical and pathological findings in patients with lupus
      nephritis: a five-year experience in Iran.
AB  - Lupus nephritis (LN) is the most common and serious manifestation of systemic
      lupus erythematousus (SLE). The World Health Organization (WHO) and International
      Society of Nephrology/Renal Pathology Society (ISN/RPS 2003) classifications tend
      to correlate with the clinical syndrome and provide valuable information
      regarding prognosis and guideline for treatment. We retrospectively studied
      patients with biopsy proven lupus nephritis at our center from 1999 - 2003 to
      find whether clinical and laboratory parameters used to evaluate how close the
      diagnosis correlated with WHO and/ or ISN/RPS 2003 classification. There were 144
      patients of whom 84.7 % were females with a mean age of 25.6 +/- 10.3 years at
      the time of renal biopsy. The most frequent SLE presenting features were
      arthralgia, edema and hypertension. WHO class IV and ISN/RPS class IV were
      compatible with these most frequent SLE presenting features in 56% and 54.9% of
      the cases, respectively. Edema, hypertension, increased BUN and Creatinine,
      increased 24 hours urine protein excretion and decreased serum albumin level were
      related with a worse class of lupus nephritis. We conclude that there is a
      correlation between some clinical and laboratory findings, and histopathological
      lupus classification on renal biopsy ,which remains indispensable in the
      management of lupus nephritis.

PMID- 18087121
TI  - Occurrence of cytomegalovirus infection and factors causing reactivation of the
      infection among renal transplant recipients: a single center study.
AB  - Reactivation of infection with the cytomegalovirus (CMV) in renal transplant
      recipients may cause significant morbidity and mortality. To evaluate factors
      associated with activation of CMV replication, we followed prospectively a group
      of 68 renal transplant recipients for 12 months. The control group consisted of
      healthy blood donors (n = 37). Sera were collected periodically from these
      patients and analyzed for the presence of specific anti-CMV antibodies. Enzyme
      linked immunoassay based on recombinant CMV proteins was used to detect the
      following antibody specificities: IgG and IgM. During the first year after
      transplantation, reactivation of CMV occurred in 48 recipients (70.6%). Detailed
      analysis did not show any association of reactivation with the type of basic
      immunosuppressive therapy, prophylactic or therapeutic use of anti-lymphocyte
      antibodies, as well as occurrence of acute rejection episodes. There was a
      borderline association (P=0.068) between the presence of CMV infection and EBV
      reactivation. In conclusion, results of our study suggest that CMV infection may
      represent a factor activating EBV replication.

PMID- 18087122
TI  - Electrocardiography and serum potassium before and after hemodialysis sessions.
AB  - This study was undertaken to assess potassium level and electrocardiographic
      (ECG) changes post hemodialysis and whether fall in potassium level during
      dialysis may potentiate cardiac arrythemia. We studied 21 chronic hemodialysis
      (HD) patients who had their serum electrolytes measured before and immediately
      after dialysis session, and ECG performed at the same time. The patients included
      14 females and 7 males with a mean age of 53.1+/-15.6 years and range from 26 to
      81 years; 9 (43%) patients were diabetics. All the patients had been on dialysis
      for a minimum of 6 months each Pre-HD serum potassium levels had no correlation
      with any ECG parameters except a negative correlation with the T wave amplitude
      r=-0.5, p=0.021. ECG parameters significantly changed post-HD; the T wave
      amplitude decreased, and the R wave amplitude increased. A comparatively higher R
      wave significantly decreased the T to R wave ratio post dialysis. The QRS
      duration and QTc interval also increased significantly. The patients with post-HD
      serum potassium of < or = 3.5 -in comparison to those with levels > 3.5 mmol/L 
      had a higher R wave amplitude and a significantly less T to R wave ratio (11.8+/
      9.7 vs 6.4+/-5.1, p=0.045 and 0.4+/-0.38 vs 1.0+/-0.97, p=0.049, respectively. In
      patients with serum potassium decrement of > 2.0 mmol/L, the T to R wave ratio
      decreased significantly, 0.32+/-0.21 vs 0.85 +/-0.26, p=0.023; The T wave
      amplitude decreased more than the rise in R wave. Multiple regression analysis
      did not reveal any relationship of pre or post HD ECG changes and serum
      potassium, serum calcium or net change in serum potassium post-HD. We conclude
      that post-HD serum potassium decrement results in a decrease in T to R wave ratio
      on ECG; this change may have an arrhythmogenic potential.

PMID- 18087123
TI  - Pre-transplant calcium-phosphate-parathormone homeostasis as a risk factor for
      early graft dysfunction.
AB  - While good organ quality and ideal transplant conditions eliminate many of the
      know factors that compromise initial graft function (IGF), poor early graft
      function (EGF) still occurs after living donor kidney transplantation (LDKT).
      Uncontrolled pre-transplant hypercalcemia and hyperparathyroidism are associated
      with impaired allograft function. Between April 2004 and January 2006, data were
      collected on 354 LDKT recipients including 252 males and 102 females, to
      determine risk factors for poor EGF, defined as either delayed or slow graft
      function (DGF or SGF). Of the 354 recipients, 318 (89%) had IGF, 22 (6.2%) had
      SGF and 14 (4%) had DGF. Donor female gender (P = 0.04) and duration on dialysis
      (P = 0.02) were associated with poor EGF. Recipients with DGF had higher serum
      phosphate (P = 0.07) and calcium x phosphate product ( P = 0.01) than recipients
      with IGF and SGF. The serum parathormone (PTH) levels were higher in recipients
      with SGF and DGF although the difference was not statistically significant (P =
      0.1). Serum calcium levels did not correlate with the occurrence of poor EGF (P =
      0.9). Our study suggests that serum phosphate and calcium x phosphate product
      serve as risk factors for DGF while serum PTH level may play a role as a risk
      factor for SGF and DGF.

PMID- 18087124
TI  - Outcome of patients without any immunosuppressive therapy after renal allograft
      failure.
AB  - Continuation of low-dose maintenance immunosuppressive therapy in end-stage renal
      allografts (ESRAs) that are left in situ is controversial. We studied the outcome
      of 85 patients (mean age 33.3 +/- 13.4 and range of 12-56 years) on hemodialysis
      with ESRAs, and without immunosuppressive therapy in our center from July 1991 to
      July 2003. Twelve (14.1%) study patients underwent allograft nephrectomy within a
      mean interval of 44.5 months after graft failure. The rest of the patients
      remained stable without fever, hematuria, graft tenderness, or localized edema
      during a mean interval of 46.5 +/- 45.2 months of follow-up. These results are
      promising and suggest that maintenance immuno-suppressive therapy in patients
      with ESRAs and on dialysis may not be necessary to avoid allograft nephrectomy.
      Prospective studies are warranted to substantiate these results.

PMID- 18087125
TI  - Inflammation and pruritus in hemodialysis patients.
AB  - Pruritus is a common problem in dialysis patients. The aim of this study was to
      determine the cause(s) of pruritus and its relationship with inflammatory
      proteins. In a cross sectional study, all patients on hemodialysis at the Emam
      Khomaine and Sina Hospital, Tehran, Iran who did not have any pruritus-producing
      skin lesions were studied. They were questioned about the occurrence of pruritus
      during the preceding two weeks. Variables including inflammatory proteins (C
      reactive protein, albumin, ferritin, transferrin, fibrinogen), hemoglobin, red
      blood cell indices, iron, iron binding capacity, transferring saturation, urea,
      creatinine, calcium, phosphorus, calcium x phosphorus product, alkaline
      phosphatase and parathormone were determined. Data were analyzed using Anova or
      Chi-square tests for evaluation of difference between variables. Of the 164
      patients studied, 80 (49%) had pruritus. Of these, 45 subjects (23.8%) had severe
      and 35 (21.3%) mild to moderate pruritus. There were no significant differences
      between groups with or without pruritus for age, sex, duration on dialysis,
      dialysis adequacy, cause of renal failure and erythropoetin usage. Mean CRP was
      16.6 mg/L; 58.5% of the patients had CRP > 10 mg/L. There was no significant
      correlation between CRP levels and presence or severity of pruritus. Also, none
      of the other inflammatory proteins revealed any significant differences. Among
      the other parameters, only the mean MCV levels were significantly different
      between the three groups (P < 0.05). Our study suggests that inflammatory
      proteins do not play any part in hemodialysis associated pruritus.

PMID- 18087126
TI  - Interstitial and glomerular renal involvement in sarcoidosis.
AB  - Sarcoidosis is a systemic disease characterized by chronic granulomatous
      inflammation. Chronic kidney disease (CKD) was reported in less than 1% of
      patients of sarcoidosis. The prevalence of tubulo-interstitial nephritis (TIN) in
      sarcoidosis varies from 7 to 27%. In this retrospective study, we present 15
      patients with interstitial or glomerular renal involvement secondary to
      sarcoidosis diagnosed in our center from 1975 to 2006. Patients were 13 (96.6%)
      females and two males with a mean age of 56.5 years. CKD was present in 14(93.3%)
      patients, proteinuria in 13(96.6%), and nephrotic syndrome in one. Pulmonary
      involvement was present in 10 (66.6%) patients. Renal biopsy performed in 12
      (80%) patients revealed TIN lesions in 10 (66.6%) patients, extracapillary
      proliferative glomerulonephritis (GN) in one, and membranous GN type 2 in
      another. Corticosteroid therapy using prednisolone 0.5 to 1 mg/kg per day was
      used in 12(80%) patients. Ten (66.6%) patients were followed up for a mean period
      of 25 months (ranged from 2 to 48 months). The outcome was favorable with 7
      (46.6%) patients improved their renal function, 6 (40%) remained with a moderate
      CKD, one normalized his renal function, and one died suddenly after 2 months of
      initiating the treatment corticosteroids. We conclude that corticosteroid
      treatment is efficient in TIN and variably efficient in GN. Patients with
      sarcoidosis may cause advanced renal failure, which renders it a serious
      nephrological condition.

PMID- 18087127
TI  - Outcome of kidney transplantation in patients with polycystic kidney disease: a
      single center study.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of end
      stage renal disease and a common indication for renal transplantation. Patients
      with ADPKD show some differences in graft outcome and complications following
      renal transplantation. This study was undertaken to evaluate the demographics,
      outcome and complications of renal transplantation in patients with ADPKD. In a
      retrospective case-control design, 51 patients with ADPKD were recognized amongst
      a total of 1200 renal transplant patients. For each case, a matched control based
      on sex, age (+/- 5 years) and type of kidney donor, was selected. All relevant
      data were gathered using patients' records and PNOT software. There were 34 males
      (66.7%) and 17 females (33.3%) with ADPKD. Mean age at transplantation was 42.6
      +/- 14.3 years and source of donor organ was predominantly live unrelated
      (72.5%). Forty patients (78.4%) had extra-renal manifestations of ADPKD, the most
      common of which were cardiac valvular disease (24 cases, 47.1%), and liver cysts
      (10 cases, 19.6%). Rejection occurred in 12 patients in the case-group (23.5%) in
      comparison to nine patients (17.6%) in the control group (p > 0.05). Twenty-nine
      cases (56.9%) did not develop any complications. The common complications noted
      after transplantation included infections (15.7% in cases vs 19.6% in controls),
      and cerebrovascular accidents (13.7% in cases vs 16.6% in controls). Patient
      outcome after short- and long-term follow-up was slightly better in the ADPKD
      population than the control group; however, it was not statistically significant.
      Also, no complication was found to occur more frequently in ADPKD patients.

PMID- 18087128
TI  - Radiological findings in renal tuberculosis: a report from northwest of Iran.
AB  - Tuberculosis (TB) of the kidney and urinary tract has non-specific symptoms and
      is easily overlooked. We performed this retrospective study to analyze different
      findings on excretory urography (IVP) of patients with renal TB. The IVP slides
      of 25 patients (14 females/11 males, age range 12-63 years) with renal TB
      diagnosed over a 20-years period were studied for the presence of characteristic
      findings. They included: renal parenchymal mass, autonephrectomy, hydronephrosis,
      ureteral stricture and dilatation, and bladder involvement and fibrosis. In our
      study, the most common findings were ureteral stricture and dilation (13/25,
      52%), bladder involvement 13/25 (52%), autonephrectomy 12/25 (48%) and renal
      parenchymal calcification 10/25 (40%). The most common combined pattern was
      ureteral stricture-dilation with contralateral autonephrectomy and bladder
      irregularities. We conclude that kidney TB remains undiagnosed until the advanced
      stages and awareness about the IVP imaging pattern could help in early diagnosis
      of this entity.

PMID- 18087129
TI  - Bladder tuberculosis after BCG therapy.
AB  - The initial treatment of bladder cancer is transurethral resection (TUR), but
      this cancer recurs at an important rate, and has 14% chance of progression after
      TUR alone. Intravesical chemotherapy with Bacillus Calmette-Guerin (BCG) is
      effective against recurrence and progression of bladder cancer. However, this
      therapeutic expose to many local and systemic side-effects. We report a case of
      63-year-old man who presented bladder tuberculosis after a BCG therapy, which
      required 6 months of antitubercular therapy.

PMID- 18087130
TI  - Calciphylaxis of both proximal and distal distribution.
AB  - Calciphylaxis is a dreaded complication of chronic renal failure characterized by
      nodular subcutaneous calcification and pain. Full tissue necrosis often leads to
      ulceration, secondary infection and high mortality rate. We herewith present a 65
      year-old Saudi gentleman who presented with multiple necrotic skin lesions of
      both proximal and distal distribution. Skin biopsy confirmed the diagnosis of
      calciphylaxis. Patient was started on sevelamer hydrochloride and low calcium
      dialysate to which he responded dramatically without the need for
      parathyroidectomy. To our knowledge, this is the first reported case of
      calciphylaxis with both proximal and distal distribution.

PMID- 18087131
TI  - A case of bladder and colonic duplication.
AB  - Duplication of the bladder is a rare congenital anomaly with an unknown
      embryological basis. A 12-year-old boy with dysuria was found to have a tri
      radiate external urethral meatus instead of a vertical slit. Cystourethroscopy
      revealed two bladders with bifid proximal urethra. Magnetic resonance imaging
      (MRI) revealed duplication of colon and bladder. He did not have any symptoms
      related to the urinary tract.

PMID- 18087132
TI  - Extensive cerebral venous thrombosis in a renal allograft recipient.
AB  - An increased risk of venous thromboembolism has been demonstrated following renal
      transplantation. Commonly reported sites have been deep vein thrombosis,
      pulmonary thromboembolism and vascular thrombosis involving the graft. Cerebral
      venous thrombosis (CVT) has not been reported in literature so far. A 36-year-old
      male patient, transplanted in Jan 2005 with normal graft functions, was admitted
      with history of headache, blurring of vision and vomiting. Examination revealed
      papilledema and no neurological deficits. Baseline investigations and analysis of
      cerebrospinal fluid were normal. Cerebral magnetic resonance venogram revealed
      extensive CVT involving superior sagittal sinus, bilateral transverse sinuses and
      the right sigmoid sinus. He was investigated for a thrombophilic disorder; serum
      homocysteine, protein C and S levels, antiphospholipid antibody and antithrombin
      III levels were done despite which no conclusive diagnosis could be arrived at.
      To our knowledge, this is the first report of extensive CVT described in a
      transplant recipient. No definite prothrombotic or predisposing factors could be
      identified in our patient and the cause of CVT remains unclear.

PMID- 18087133
TI  - Horner's syndrome following internal jugular vein dialysis catheter insertion.
AB  - Common complications that can occur following internal jugular vein
      catheterization used for hemodialysis (HD) include internal carotid artery
      puncture, thrombosis, and infection. We present a case of Horner's syndrome
      following internal jugular venous cannulation as a possible complication.

PMID- 18087134
TI  - Complete recovery of renal allograft function after sixty days of delay following
      living related transplantation.
AB  - Delayed graft function (DGF), a term employed when a newly transplanted organ
      does not function efficiently is commonly observed following cadaveric renal
      transplantation but is very rare after living related transplants. We present a
      31-year-old female recipient of a related donor kidney (mother) who had DGF
      following trans-plantation due to acute tubular necrosis, probably caused by
      partial allograft arterial thrombosis, which recovered function after 60 days.
      Appropriate use of allograft biopsy should be encouraged even in resource-limited
      settings lest the allograft be assumed to have failed irreversibly.

PMID- 18087135
TI  - Modified anterior abdominal donor nephrectomy in comparison with laparoscopic
      donor nephrectomy.
AB  - Recently with introduction of laparoscopic nephrectomy, the procedure has become
      more appealing to living donors because of smaller laparoscopic incision and
      decreased length of hospital stay. However, because of the relatively prolonged
      warm ischemia time, increased operating time, and delayed graft function, the
      current laparoscopic donor nephrectomy is still subject to further development.
      We introduced a modified anterior abdomen incision for donor nephrectomy with
      advantages of laparoscopic procedure but with shorter warm ischemia and operation
      time. In 15 donors, a 10 cm incision was performed in the upper side of the
      abdomen between the rectus muscle and the tip of the ribs, while the donor was in
      flank position. Then, the kidney was exposed and freed followed by ureter
      nephrectomy. Afterwards, the abdominal wall was repaired without drain. The time
      of operation (from incision skin to suturing of skin) was from 1-1.5 hours with a
      few seconds of warm ischemia time. The donors experienced tolerable pain and all
      of them were discharged from hospital two days post operation. All grafts in
      recipients started to diurese immediately. Cosmetic appearance of wounds after
      operation and six months later were good. In conclusion, the modified anterior
      abdominal incision is safe and comparable with the conventional laparoscopic
      procedure in the size of the incision, the cosmetic appearance, the incision
      pain, and time of discharge. It may be advised as an alternative laparoscopic
      nephrectomy procedure.

PMID- 18087136
TI  - Tumoral calcinosis of the elbow in a long-term hemodialysis patient.

PMID- 18087138
TI  - Organ sharing in Saudi Arabia: a proposal.

PMID- 18087137
TI  - Fractional excretion of uric acid as a therapeutic monitor in cerebral salt
      wasting syndrome.

PMID- 18087139
TI  - Prevalence and risk factors for hepatitis C virus infection in hemodialysis
      patients in an Iraqi renal transplant center.
AB  - Hepatitis C virus (HCV) infection has been recognized as an emerging problem in
      dialysis patients and its prevalence varies considerably among different areas of
      the world. The prevalence of HCV infection in hemodialysis (HD) patients and its
      associated risk factors is not well documented in our country. We therefore
      performed this study aiming to discuss prevention of further transmission of HCV
      infection among our patients. Between September 2003 and September 2005, 169
      patients with end-stage renal failure on HD at the Renal Transplant Center,
      Medical City Teaching Hospital, Baghdad, were involved in this prospective study.
      There were 102 (60.4%) males, and 67 (39.6%) females, with age ranging from 14-67
      years. Anti-HCV antibodies were positive in 12 of these patients (7.1%). Female
      gender, age >or = 60 years, dialysis duration < or = six months, history of
      having received blood transfusion(s), and < 9 hours per week of HD were
      significant predictors of anti-HCV positivity. We conclude that adherence to
      universal infection precautions, regular HCV screening of transfusions and of
      patients on HD and the use of separate machines for those who are anti-HCV
      positive, are important factors. To further reduce the prevalence in our
      patients, erythropoietin should replace blood transfusions as also testing for
      HCV RNA using polymerase chain reaction before starting HD.

PMID- 18087140
TI  - Evaluation of secondary hyperparathyroidism in patients undergoing hemodialysis.
AB  - Renal osteodystrophy is a complication of chronic kidney disease (CKD) that
      present in low and high turnover patterns. This disorder has a key role in the
      disability of CKD patients in whom early diagnosis and treatment can result in
      better outcome. We studied hyperparathyroidism prevalence and its relationship
      with renal osteodystrophy in our advanced CKD population. We included 80 patients
      (of whom 44 (55%) were diabetic) during 6 months period. The patients answered a
      questionnaire about symptoms related to bone disease and blood levels of
      parathormone (PTH), calcium, phosphorus, and alkaline phosphatase were obtained,
      in addition to hand and skull radiographs in all the study patients. Prevalence
      of clinically evident hyperparathyroidism in our patients was 45%.
      Hyperparathyroidism had significant relationship with alkaline phosphatase and
      radiological findings, but did not have a significant relationship with dialysis
      duration, age, sex, familial history, diabetes mellitus, or hypertension. We
      conclude that secondary hyperparathyroidism is prevalent in our dialysis
      population and has high correlation with serum alkaline phosphatase levels and
      radiological changes.

PMID- 18087141
TI  - Malignant renal tumors in adults: a ten-year review in a Nigerian hospital.
AB  - This study was undertaken to determine the age, sex, pattern of presentation,
      histopathology and outcome of management of adult patients with malignant renal
      tumors (MRT) in Nigeria. Using hospital records, a retrospective study was
      performed covering the period between January 1997 and December 2006. A total of
      18 adult patients had been diagnosed to have MRT during this period. Information
      extracted and analyzed included the age of the patient, sex, presentation,
      investigations, type of histopathology, management and duration of follow-up. The
      mean age of the study patients was 47.5 years (range 16-80 yrs). The male: female
      ratio was 13 : 5 and the mean duration of symptoms was 43.6 weeks (range 2-104
      wks). Sixteen patients (88.9%) presented in advanced stage. Symptoms included
      loin pain in 17 (94.4%), abdominal swelling in 15 (83.3%), weight-loss in 13
      (72.2%) and hematuria in nine (50.0%). Ultrasound and intravenous urography
      assisted greatly in making the diagnosis. Thirteen patients (72.2%) underwent
      radical nephrectomy, tumors were not resectable in two (11.1%) and three others
      (16.7%) were deemed unfit to undergo surgery. The average tumor mass removed at
      surgery was 1.884 Kg (range 0.48-3.82 Kg). Renal cell carcinoma (RCC) accounted
      for 13 of the tumors (72.2%). Surgical complications include primary-hemorrhage,
      septicemia and tumor recurrence in one patient each (7.6%). Morbidity and
      mortality rates were 7.6% each. The average post-operative hospital stay and
      follow-up duration were 9.3 days and 37.5 months respectively. Our study suggests
      that RCC is the major MRT in our community. Most cases still present late with
      loin pain and swelling, weight loss and hematuria. This late presentation and
      sarcomatous type of tumor have negative influence on prognosis. Radical
      nephrectomy is beneficial in operable, locally advanced, non-metastatic MRT.

PMID- 18087142
TI  - Organ and tissue transplantation in Iran.

PMID- 18087143
TI  - Demographics and social factors associated with acceptance of treatment in
      patients with chronic kidney disease.
AB  - Dialysis and transplantation have prolonged survival and quality of life in
      patients with chronic kidney disease (CKD). This is an exploratory/descriptive
      study, looking into the socio-demographic profile and social factors in these
      patients associated with acceptance of therapy. Association between attitudes and
      demographics were examined. A total of 670 patients with CKD were prospectively
      evaluated during the years 2000-2003 and based on the degree of renal failure,
      were categorized into conservative therapy, dialysis alone, or transplantation. A
      detailed psycho-social assessment and counseling regarding the treatment options
      was done. The mean age of the study patients was 49.27 +/- 16.7 years. Of the
      study patients, 66.7% were males, 70.6% were married, 40% were undergraduates,
      34% were employed, 41.6 and 37.3% were respectively from low- and middle-income
      groups, 60% lived in nuclear families and 64% had an urban background. Patients
      with CKD Stages II - IV (37.3%) were advised conservative treatment, while CKD
      Stage V patients were advised dialysis alone in 35.5% and dialysis and
      transplantation in 64.5%. The major psycho-social factors negatively influencing
      the acceptance of treatment were finance (69.3%), logistics (66.0%), no willing
      donors (11.0%), no medically fit donors (13.0%) and/or lack of social support
      (17.0%). Statistically significant association was noted between attitudes and
      marital status (p < 0.05, education and domicile (p = 0.05), occupation, income
      and family type (p < 0.05). Our study suggests that finance is one of the
      important factors deciding the acceptance of treatment. Social factors negatively
      affecting were logistics, lack of willing and medically fit donors and lack of
      social support.

PMID- 18087144
TI  - Amyloidosis and vascular thrombosis.
AB  - Amyloidosis is a rare systemic disorder of protein metabolism with progressive
      extra-cellular deposition of insoluble fibrillary protein, disorganization of
      tissue architecture, and subsequent organ dysfunction. Primary amyloidosis is the
      most common form of this disorder, however, it can develop secondary to plasma
      cell dyscrasias such as multiple myeloma (MM); 10-15% of MM patients may develop
      amyloidosis of vital organs. Amyloidosis is usually associated with bleeding, but
      less commonly with thrombosis. We present a 52-year-old Saudi female with
      amyloidosis secondary to multiple myeloma. She presented with both venous and
      extensive arterial thrombosis. Although relatively rare, plasma cell dyscrasias
      such as amyloidosis and multiple myeloma could present with thrombotic rather
      than hemorrhagic complications.

PMID- 18087146
TI  - Acute lymphoblastic leukemia in a patient with chronic cyanoacrylate exposure.
AB  - Environmental agents have long been thought to be linked to the development of
      malignancies. Due to the difficulty in identifying and verifying exposures to
      such agents, only a few chemical compounds are clearly linked to malignancies. We
      report here the case of a 36-year-old man with pre-B cell acute lymphoblastic
      leukemia. This patient was using industrial strength glue to reattach a chipped
      tooth for approximately 1 year, and such use was associated with chronic exposure
      of his oral mucosa to this glue. This case raises the possibility that chronic
      exposure to cyanoacrylates, the adhesive agents in industrial strength glue, may
      be associated with the development of acute lymphoblastic leukemia in humans.

PMID- 18087147
TI  - Serum albumin, body weight and inflammatory parameters in chronic hemodialysis
      patients: a three-year longitudinal study.
AB  - BACKGROUNDS AND AIMS: The present study aimed at making prospective longitudinal
      measurements of nutritional and inflammatory parameters to determine whether
      nutritional and inflammatory status decline or increase over time in a cohort of
      prevalent hemodialysis patients, and to evaluate which factors influence eventual
      changes. PATIENTS: 64 hemodialysis patients were followed at 0, 3, 6, 9, 12, 15,
      18, 21, 24, 27, 30, 33, and 36 months. At each follow-up visit, dry body weight,
      serum albumin, serum total cholesterol, total white blood cells, total lymphocyte
      count, serum glucose, C-reactive protein, ferritin, fibrinogen, hemoglobin, and
      weekly erythropoietin dose were assessed. MAIN OUTCOME MEASURES: Changes in
      nutritional and inflammatory parameters over time. RESULTS: 43 patients completed
      the study at 36 months. Mean serum albumin levels (g/dl) improved significantly
      between baseline (3.76 +/- 0.24) and 36 months (3.93 +/- 0.27) (F = 4.005; p =
      0.0009). Dialytic age was significantly associated with changes of serum albumin
      (F = 2.797; p = 0.028). The mean dry weight slightly remained stable over time (F
      = 1.473; p = 1.0) as well as the level of total cholesterol (p = 0.77) and
      lymphocyte count (F = 1.539; p = 0.186). Over time, the levels of C-reactive
      protein tended to decrease, although the differences were not statistically
      significant (F = 1.332; p = 0.19). Over time, the serum level of fibrinogen (F =
      0.422; p = 0.17) and ferritin (F = 0.314; p = 0.52) remained stable. The number
      of white blood cells significantly decreased over time (F = 4.691; p = 0.0079)
      and dialytic age (F = 3.214; p = 0.015) was the variable significantly associated
      with such decline. The hemoglobin levels (F = 1.423; p = 0.14) and the weekly
      erythropoietin dose did not change significantly during the study (F = 1.019; p =
      0.61), nor did the serum glucose levels (F = 1.231; p = 0.10). CONCLUSION: These
      results support the hypothesis that end-stage renal disease and HD are not
      necessarily associated with deterioration of the nutritional status over time.

PMID- 18087148
TI  - Development of vestibular evoked myogenic potentials in preterm neonates.
AB  - Our recent study successfully recorded vestibular evoked myogenic potential
      (VEMP) responses in full-term newborns. However, when VEMP responses are elicited
      in preterm neonates remains unclear. This study employed the VEMP test in 27 low
      risk preterm and 25 healthy full-term neonates without sedation to investigate
      the development of VEMP response after birth. Fourteen (26%) of 54 ears in
      preterm neonates exhibited VEMP responses, a response rate significantly lower
      than that of full-term neonates (72%). The mean latencies of peaks p13 and n23 in
      the preterm group were significantly longer than those in the full-term group.
      Analysis of variable parameters for present VEMPs in pre- and full-term neonates
      revealed that the cutoff values of body weight were 2.26 and 2.82 kg, and that
      those of postmenstrual age were 37.1 and 38.4 weeks, respectively. Both body
      weight and postmenstrual age were significantly negatively correlated with p13
      and n23 latencies but not with p13-n23 amplitude. In conclusion, present VEMPs
      can be anticipated when the body weight of pre- and full-term neonates reaches
      >2.26 and 2.82 kg, respectively. It indicates that the sacculocollic reflex
      develops in the same manner, but the difference in response rate between full-
      and pre-term neonates may, at least in part, correlate with muscle bulk and
      strength, relative to the body weight adequate for the VEMP response.

PMID- 18087149
TI  - Cyclosporin A induces peritoneal fibrosis and angiogenesis during chronic
      peritoneal exposure to a glucose-based, lactate-buffered dialysis solution in the
      rat.
AB  - BACKGROUND/AIMS: Cyclosporin A (CsA) stimulates the development of fibrosis. We
      investigated whether CsA contributes to peritoneal alterations induced by long
      term exposure to dialysis solutions. METHODS: Ten rats received peritoneal
      infusion of dialysis solution and oral CsA for 8 weeks. Eight received only the
      dialysis solution (controls). Peritoneal function was assessed at 8 weeks
      followed by sacrifice. The number of vessels was counted, fibrosis was assessed
      and hydroxyproline was determined. PCR was performed for vascular endothelial
      growth factor (VEGF), connective tissue growth factor (CTGF) and transforming
      growth factor-beta (TGF-beta). RESULTS: Histology revealed more fibrosis,
      hydroxyproline and vessels (thick walled) in CsA-exposed animals. Peritoneal
      transport was not different. The mRNA content of TGF-beta, CTGF and VEGF was
      higher in CsA. CONCLUSION: CsA combined with exposure to dialysis solutions was
      associated with increased peritoneal fibrosis and angiogenesis.

PMID- 18087150
TI  - Pigmentation markers: more color in the picture of uremic toxicity?

PMID- 18087151
TI  - Impact of different toothpastes on the prevention of erosion.
AB  - The aim of the present study was to test the impact of different toothpastes on
      the prevention of erosion. Enamel demineralization and remineralization were
      monitored using surface microhardness (SMH) measurements. Human enamel specimens
      were treated following two different procedures: (1) incubation in toothpaste
      slurry followed by acid softening and artificial saliva exposure; (2) acid
      softening followed by incubation in toothpaste slurry and artificial saliva
      exposure. For the control procedure, toothpaste treatment was excluded. The
      following toothpastes were tested: Zendium, Sensodyne Proschmelz (Pronamel),
      Prodent Rocket Power, Meridol and Signal active. Normalized SMH values compared
      to the baseline (= 1.00) after 1-hour artificial saliva exposure for procedure 1
      (respectively for procedure 2) were as follows (mean: 95% CI): Sensodyne
      Proschmelz 0.97: 0.93, 1.00 (0.92: 0.90, 0.94), Zendium 0.97: 0.94, 1.00 (0.89:
      0.83, 0.95), Meridol 0.97: 0.94, 1.00 (0.94: 0.92, 0.96), Signal active 0.94:
      0.91, 0.97 (0.95: 0.91, 0.99), Prodent Rocket Power 0.92: 0.90, 0.94 (0.93: 0.89,
      0.97) and control 0.91: 0.88, 0.94. Further exposure to artificial saliva for up
      to 4 h showed no significant improvement of SMH. Regression analyses revealed a
      significant impact of the applied procedure. Incubation in toothpaste slurries
      before the acid challenge seems to be favorable to prevent erosion. None of the
      tested toothpastes showed statistically significant better protection than
      another against an erosive attack.

PMID- 18087152
TI  - Neuropsychiatric manifestations in mild cognitive impairment: a systematic review
      of the literature.
AB  - BACKGROUND: Mild cognitive impairment (MCI) is an etiologically heterogeneous
      condition that is characterized by cognitive changes without impairment of
      activities of daily living and insufficient to represent dementia. MCI is an
      important risk state for dementia. Neuropsychiatric symptoms may be present in
      MCI. METHODS: We executed a PubMed search for articles on the neuropsychiatric
      manifestations in MCI and reviewed their findings. RESULTS: Behavioral
      abnormalities are reported in 35-75% of MCI patients with the most common being
      depression, apathy, anxiety and irritability. The observed variability in symptom
      prevalence can be explained by the different sampling methods, MCI diagnostic
      criteria and behavioral instruments used. There is a compelling body of evidence
      that MCI patients with behavioral features are more prone to develop Alzheimer's
      disease (AD) than patients without these features. CONCLUSIONS: Neuropsychiatric
      symptoms are common features of MCI. The behavioral changes observed in MCI are
      similar to those of AD and may help identify the subgroup of MCI patients with
      prodromal AD. Large prospective longitudinal studies would greatly contribute to
      our understanding of the epidemiology, diagnostic and prognostic value of the
      neuropsychiatric features in MCI.

PMID- 18087153
TI  - Dementia diagnostics in primary care: a representative 8-year follow-up study in
      Lower Saxony, Germany.
AB  - AIM: To investigate whether primary-care physicians' competency regarding
      dementia diagnostics improved from 1993 to 2001. METHODS: In a representative
      follow-up survey 122 out of 170 (71.8%) family physicians (FPs) were randomly
      assigned to 2 written case samples presenting patients with slight memory
      impairment (case 1a: female vs. case 1b: male) and moderate dementia [vascular
      type (case 2a) vs. Alzheimer's disease (case 2b)]. Potential diagnostic workup
      was inquired by a structured face-to-face interview. RESULTS: 'Basic' diagnostics
      like history taking or laboratory investigations were considered in the first
      place. In case 1, neuropsychological screening was significantly more frequently
      considered at follow-up (19.3% in 1993 vs. 31.1% in 2001); it still would have
      been applied rarely in case 2 (2a: 14.1 vs. 14.8%; 2b: 23.5 vs. 24.6%).
      Neuroimaging remained not to be considered as a standard procedure, and only a
      minority of FPs would have performed a screening for depression (2001: 1a: 6.7%;
      1b: 11.3%; 2a: 0.0%; 2b: 1.6%). CONCLUSIONS: With regard to dementia diagnostics
      in primary care, guideline adherence remained low at follow-up. Structured
      training efforts aiming at FPs appear to be necessary.

PMID- 18087156
TI  - Low levels of endotoxin enhance allergen-stimulated proliferation and reduce the
      threshold for activation in human peripheral blood cells.
AB  - BACKGROUND: Endotoxins, comprised of bacterial cell wall lipopolysaccharides
      (LPS), have been reported to have both protective and exacerbating effects on the
      development and maintenance of allergic disease in humans and on markers of
      allergic inflammation in animal models of allergy. In this study, we investigated
      the effect of low concentrations of LPS on human peripheral blood mononuclear
      cells (PBMC) stimulated with the major cat allergen Fel d 1. METHODS: Extensive
      purification of recombinant (r) Fel d 1 yielded essentially endotoxin-free rFel d
      1 (0.2 ng LPS /mg protein). PBMCs prepared from 15 subjects having IgE to cat
      (>0.7 kU(A)/l) and 8 subjects IgE negative to cat were stimulated with 2, 10 or
      25 microg/ml of rFel d 1 in the presence or absence of 50 pg/ml LPS.
      Proliferation was measured after 7 days of culture and supernatants were analyzed
      for IFNgamma, IL-5 and IL-10. RESULTS: LPS (50 pg/ml) increased rFel d 1
      stimulated proliferation of PBMCs both from subjects IgE-positive and subjects
      negative to cat allergens. PBMCs from 13 of the subjects did not proliferate in
      response to stimulation with 2 and 10 microg/ml rFel d 1 alone but did so in the
      presence of LPS. Moreover, LPS increased the levels of rFel d 1-stimulated
      IFNgamma in cultures from cat-negative subjects, IL-5 from cat-positive subjects
      and IL-10 from both groups. CONCLUSION: Very low doses of LPS enhance
      proliferation and decrease the apparent threshold level for cell activation,
      prompting careful evaluation of allergen stimulated T cell activation in vitro.

PMID- 18087157
TI  - A neonatal swine model of allergy induced by the major food allergen chicken
      ovomucoid (Gal d 1).
AB  - BACKGROUND: Food allergy is a serious health problem for which a validated
      outbred large animal model would be useful in comparative investigations of
      immunopathogenesis and treatment and in testing hypotheses relevant to complex
      host-environmental interactions in predisposition to and expression of food
      allergy. OBJECTIVE: To establish a neonatal swine model of IgE-mediated allergy
      to the egg protein ovomucoid (Ovm) that may mimic human allergy. METHODS: In
      order to induce Ovm sensitivity, piglets at days 14, 21 and 35 of age were
      sensitized by intraperitoneal injection of 100 microg of crude Ovm and cholera
      toxin (50, 25 or 10 microg). Controls received 50 microg of cholera toxin in
      phosphate-buffered saline. The animals were challenged orally on day 46 with a
      mixture of egg white and yoghurt. Outcomes were reported as direct skin tests,
      clinical signs, IgG-related antibody and passive cutaneous anaphylaxis. RESULTS:
      Sensitized pigs developed immediate wheal and flare reactions, and after oral
      challenge, sensitized but not control animals displayed signs of allergic
      hypersensitivity. Serum IgG-related, Ovm-specific antibodies were detected only
      in the sensitized pigs and IgE-mediated antibody response to Ovm was confirmed by
      positive passive cutaneous anaphylaxis reactions induced by sera of sensitized
      but not by heat-treated sera from Ovm-sensitized pigs or sera of unsensitized
      control pigs. CONCLUSION: The present results confirm induction of Ovm-specific
      allergy in pigs and provide opportunity to investigate allergic predisposition
      and immunopathogenesis of IgE-induced Ovm allergy using outbred neonatal swine.
      This may better simulate allergic disease in humans and allow investigation of
      candidate prophylactic and therapeutic approaches.

PMID- 18087158
TI  - Measurement of lipid transfer protein in 88 apple cultivars.
AB  - BACKGROUND: Fruits are a major cause of food allergy in adults. Lipid transfer
      proteins (LTP) are implicated in severe allergic reactions to fruits, but little
      is known about LTP content in different cultivars. OBJECTIVE: Determination of
      the levels of LTP in a wide range of apple cultivars. METHODS: LTP was measured
      in apples from 53 cultivars grown in Italy and 35 grown in The Netherlands, using
      three different immunoassays: a competitive ELISA (cELISA), a sandwich ELISA
      (sELISA) and a RAST inhibition (RI). Selected cultivars were evaluated using the
      basophil histamine release test (BHR), skin prick test (SPT) and double-blind,
      placebo-controlled food challenge (DBPCFC). RESULTS: LTP levels measured with the
      three immunoassays were significantly correlated, as judged by Pearson's
      correlation (0.61 < Rp < 0.65; p < 0.0001), but differed with respect to the
      actual quantities: 3.4-253.2 (sELISA), 2.7-120.2 (cELISA) and 0.4-47.3 microg/g
      tissue (RI). Between cultivars, LTP titers varied over about a two-log range.
      Pilot in vitro and in vivo biological testing (BHR, SPT and DBPCFC) with selected
      cultivars supported the observed differences in LTP levels. CONCLUSIONS: Around
      100-fold differences in LTP levels exist between apple cultivars. Whether the
      lowest observed levels of LTP warrant designation as hypo-allergenic requires
      more extensive confirmation by oral challenges. Determination of cultivar
      variation in LTP levels provides important information for growers and consumers.
      Comparison to earlier reported Mal d 1 levels in the same cultivars reveals that
      a designation as low allergenic does not always coincide for both allergens.

PMID- 18087159
TI  - Upregulation of the release of granulocyte-macrophage colony-stimulating factor
      from keratinocytes stimulated with cysteine protease activity of recombinant
      major mite allergens, Der f 1 and Der p 1.
AB  - BACKGROUND: Although exposure to mite allergens is an important risk factor for
      the production of IgE and is associated with various allergic diseases, there has
      been uncertainty as to the route of exposure by which sensitization occurs.
      Cystatin A is a skin-derived dominant inhibitor against proteolytic activity of
      major mite allergens, Der f 1 and Der p 1, and blocks the upregulation of IL-8
      release from human keratinocytes stimulated with the allergens. We analyzed
      whether the stimulation of keratinocytes with the allergens upregulates the
      release of granulocyte-macrophage colony-stimulating factor (GM-CSF), which has
      many actions relevant to allergic diseases including atopic dermatitis, and if
      so, whether cystatin A can block this process. METHODS: Normal human
      keratinocytes and the human keratinocyte cell line HaCaT were stimulated with
      recombinant group 1 allergens in the absence or presence of cystatin A. RESULTS:
      Stimulation with the recombinant allergens upregulated the release of GM-CSF from
      normal human keratinocytes in a culture with high calcium concentration and HaCaT
      cells, which could be inhibited by the addition of cystatin A. The allergens
      exhibiting proteolytic activity did not digest cystatin A. Proteolytic activity
      of recombinant Der f 1 was partially regenerated after incubation with
      keratinocytes even without preactivation by L-cysteine. CONCLUSION: Proteolytic
      activity of recombinant Der f 1 and Der p 1 upregulates GM-CSF and IL-8 release
      from keratinocytes in vitro, suggesting possible contributions to sensitization
      through the skin and the perpetuation of atopic dermatitis, as well as a
      homeostatic role for cystatin A against inflammation of the skin.

PMID- 18087160
TI  - Roles of galectin-9 in the development of experimental allergic conjunctivitis in
      mice.
AB  - BACKGROUND: Galectin-9 was recently identified as a ligand for Tim-3, which
      negatively regulates Th1 cells. Here, we investigated whether administration of
      anti-galectin-9 antibodies (Abs) affects the development of murine experimental
      allergic conjunctivitis (EC), a Th2-mediated disease. METHODS: EC was induced in
      BALB/c mice by active immunization with ragweed (RW) followed by RW challenge in
      eye drops. Normal rat IgG (nrIgG) or anti-galectin-9 Ab was injected
      intraperitoneally into the mice either during the induction phase treatment or
      effector phase treatment. Alternatively, Abs were injected into the
      subconjunctival space during the effector phase. To evaluate in vitro effects of
      anti-galectin-9 Abs, splenocytes from RW-sensitized mice were cultured in vitro
      with RW in the presence of nrIgG or anti-galectin-9 Abs. To induce EC, these
      splenocytes were transferred into naive BALB/c mice followed by RW challenge.
      RESULTS: Treatment with anti-galectin-9 Abs in vivo during either the induction
      or effector phase did not significantly affect the severity of EC. However, when
      the splenocytes from RW-primed mice treated with anti-galectin-9 Abs during the
      induction phase were stimulated in vitro and adoptively transferred into naive
      recipients, they induced significantly severer EC. In contrast, when RW-primed
      splenocytes were restimulated in vitro with RW in the presence of anti-galectin-9
      Abs and then adoptively transferred, they induced less severe EC and produced
      significantly less IL-5 and IL-13 and more IFN-gamma compared to nrIgG-treated
      control splenocytes. CONCLUSIONS: These observations may reflect the fact that
      galectin-9 not only regulates T-cell function, it is also involved in many other
      biological functions.

PMID- 18087161
TI  - Genome-wide profiling of antigen-induced time course expression using murine
      models for acute and chronic asthma.
AB  - BACKGROUND: Asthma is a complex-trait disease caused by complicated interactions
      among multiple genetic and environmental risk factors. The clinical symptoms of
      asthma, such as periodic airway obstruction, hyperresponsiveness and mucus
      hypersecretion, are mediated by acute and chronic bronchial inflammation.
      METHODS: To better understand the mechanisms by which allergen-induced acute
      inflammation leads to chronic asthma accompanied by irreversible airway
      remodeling, we analyzed time course transcriptional responses in the lungs of
      model mice that were exposed to aerosolized ovalbumin for up to 9 weeks after an
      initial sensitization. RESULTS: We observed increased levels of total plasma IgE
      and histological changes in lung tissues from the ovalbumin-treated mice, which
      is consistent with the typical inflammatory phenotypes of asthma pathogenesis.
      Our oligonucleotide microarray analyses revealed a total of 776 differentially
      expressed genes induced by antigenic challenge (> or =1.5-fold change, p < 0.05).
      Of these genes, most of the immune-responsive genes were transiently up-regulated
      in the early phase of the allergen treatment (within a week) with a concomitant
      up-regulation of genes involved in mucus production. These genes were not
      differentially regulated in the mice challenged for a longer period of time (up
      to 6 weeks). We also identified some of the genes implicated in extracellular
      matrix remodeling, for which the time course expression did not necessarily
      coincide with the expression patterns of immune-responsive genes. CONCLUSION: Our
      data suggest that there is a complex interregulatory genetic network associated
      with the structural changes that accompany the progression of the allergic
      inflammatory reaction in chronic asthma.

PMID- 18087162
TI  - Home exposures to environmental tobacco smoke and allergic symptoms among young
      children in Singapore.
AB  - BACKGROUND: Research relating environmental tobacco smoke (ETS) exposures have
      focused on childhood asthma. There have been fewer studies with conflicting
      results performed on associations of ETS exposures with allergic symptoms. We are
      interested to see if ETS exposures in the homes are associated with allergic
      symptoms among preschool children in Singapore where public smoking is banned.
      METHODS: A cross-sectional study adopting an expanded and modified ISAAC
      (International Study on Asthma and Allergies in Childhood) questionnaire for the
      evaluation of asthma and allergies was conducted on 6,794 children attending 120
      randomly selected child care centers. Specific information on demographics and
      ETS exposures was obtained. Adjusted prevalence ratios (PRs) and 95% confidence
      intervals (CIs) were determined using Poisson multivariate regression with a log
      link function and robust variance estimates as recommended for cross-sectional
      studies. RESULTS: The response proportion was 70.0%, and 4,759 children from 97
      centers participated. After adjusting for covariates, it was found that home ETS
      exposure was associated with increased risks of current symptoms of rhinitis (PR
      1.23; 95% CI 1.01-1.50) and rhinoconjunctivitis (PR 1.79; 95% CI 1.26-2.54).
      These associations followed dose-response trends with respect to number of
      cigarettes smoked or smokers in the homes. Home ETS exposures were also
      associated with higher PRs of wheeze, nocturnal cough and doctor-diagnosed
      asthma. Compared with paternal smoking, higher risks of the above outcomes were
      found for maternal smoking. CONCLUSION: Home ETS exposure is a risk factor
      associated with rhinitis and asthma among preschool children.

PMID- 18087163
TI  - Basophil histamine release decreases during omalizumab therapy in allergic
      asthmatics.
AB  - BACKGROUND: Omalizumab is an established add-on therapy efficacious in allergic
      diseases with additional anti-inflammatory activity in the treatment of asthma.
      The evaluation of responders to anti-IgE treatment is critical to maximize
      benefit/risk/cost ratio. The aim of the study was to monitor the efficacy of anti
      IgE treatment by ex vivo basophil histamine release. METHODS: Seventeen patients
      with allergic asthma were enrolled and received omalizumab at a dose of > or
      =0.016 mg/kg/IgE every 4 weeks. Histamine release from basophils was evaluated
      fluorometrically after dose-dependent allergen challenge at baseline and after 16
      weeks of treatment. Maximal histamine release and cellular sensitivity to the
      allergen were calculated. Clinical measurements consisted of body
      plethysmography, skin prick test, beta2-agonist usage, serum free IgE levels,
      peripheral eosinophils and investigator ratings of global evaluation of treatment
      effectiveness. RESULTS: Maximal histamine release and cellular sensitivity to the
      allergen were significantly decreased in the omalizumab group compared to
      placebo. These changes were accompanied by significant changes in the clinical
      markers airway resistance, beta-agonist usage, skin prick test wheal area and
      investigator ratings of global evaluation of treatment effectiveness.
      CONCLUSIONS: Omalizumab therapy decreases basophil histamine release and cellular
      sensitivity with high effectivity of 95.8% (median). The decline of ex vivo
      basophil responses does not always parallel individual clinical improvement.
      Basophil-based stimulation tests should be further evaluated before being
      regarded as useful parameters monitoring omalizumab therapy.

PMID- 18087164
TI  - Immediate hypersensitivity elicits renin release from cardiac mast cells.
AB  - BACKGROUND: We recently reported that murine and cavian heart mast cells are a
      unique extrarenal source of renin. Ischemia/reperfusion releases this renin
      leading to local angiotensin formation and norepinephrine release. As mast cells
      are a primary target of hypersensitivity, we assessed whether anaphylactic mast
      cell degranulation also results in renin and norepinephrine release. METHODS:
      Hearts isolated from presensitized guinea pigs were challenged with antigen.
      RESULTS: Cardiac anaphylaxis was characterized by mast cell degranulation,
      evidenced by beta-hexosaminidase release and associated with renin and
      norepinephrine release. Mast cell stabilization with cromolyn or lodoxamide
      markedly attenuated the release of beta-hexosaminidase, renin and norepinephrine.
      Renin inhibition with BILA2157 did not affect mast cell degranulation, but
      attenuated norepinephrine release. CONCLUSIONS: Our findings disclose that
      immediate-type hypersensitivity elicits renin release from mast cells, activating
      a local renin-angiotensin system, thereby promoting norepinephrine release. As
      renin is stored in human heart mast cells, allergic reactions could initiate
      renin release, leading to local angiotensin formation and hyperadrenergic
      dysfunction.

PMID- 18087165
TI  - A randomized controlled trial of sublingual immunotherapy for Japanese cedar
      pollinosis.
AB  - BACKGROUND: Japanese cedar pollen represents an important and unique allergen.
      Sublingual immunotherapy (SLIT) has been suggested to be a highly effective route
      of desensitization against a variety of allergens. However, little information is
      available about its use in cedar pollen allergy. METHODS: A blinded randomized,
      placebo-controlled trial employing SLIT for cedar pollinosis was conducted over a
      period of 6 months. Sixty-seven subjects were enrolled and the symptom scores
      during the pollen season were evaluated by a symptom diary, measurement of cedar
      specific IgE and IgG4, and determination of Cry j-specific Th2 clones before SLIT
      and before and after the pollen season. RESULTS: No major adverse effects were
      observed in either group. The serum-specific IgG4 activity increased
      significantly after SLIT in the active group. The active group also exhibited
      significantly lower symptom scores compared to the placebo. The specific Th2
      clone sizes were not significantly different between the groups before the pollen
      season. However, an increase in the clone size was observed after the pollen
      season in the placebo group, but not in the active group. CONCLUSION: Use of SLIT
      for Japanese cedar pollinosis was found to be safe and associated with an
      increase in cedar-specific IgG4 levels. Such therapy inhibited the increase in
      Cry j-specific Th2 clone size induced by pollen exposure. Finally, use of SLIT
      resulted in significant improvement of the clinical symptoms of cedar pollinosis
      in this patient population. These observations suggest that SLIT may offer
      another safe approach to the management of cedar pollinosis.

PMID- 18087166
TI  - Anaphylaxis from the influenza virus vaccine.
AB  - BACKGROUND: Allergic reactions to the influenza vaccine are uncommon and usually
      associated with sensitivity to egg or gelatin. The aim of this study was to
      report the case of anaphylaxis to the influenza vaccine. METHODS: Allergy
      percutaneous skin testing, serum specific IgE testing and IgE immunoblotting were
      performed to the influenza vaccine, egg, and gelatin. RESULTS: Percutaneous skin
      testing to the influenza vaccine and gelatin were positive and egg (white, whole,
      and yolk) was negative. Immunocap serum-specific IgE testing to egg (white,
      whole, and yolk) and gelatin were negative (<0.35 kU/l). IgE immunoblots were
      performed with 2 cord blood serums and the patient's serum at a 1:20 dilution
      against 10 microg of the Fluzone influenza vaccine. The patient's IgE immunoblot
      showed a protein band at 100 kDa which is similar to the molecular weight of
      gelatin protein, a 68-kDa protein which is similar to the molecular weight of
      hemagglutinin protein from the influenza vaccine, and a 45-kDa protein band that
      is similar to the molecular weight of ovalbumin protein from chicken embryo/egg.
      CONCLUSION: Based on clinical symptoms, skin testing, Immunocap testing and
      immunoblot evaluation, we feel that our patient is allergic to the infectious
      agent in the influenza vaccine as well as gelatin and ovalbumin in egg.

PMID- 18087167
TI  - Hospitalizations for anaphylaxis in Florida: analysis of month of discharge.

PMID- 18087168
TI  - Persistent agonist-induced vasoconstriction is not required for angiotensin II to
      mediate inward remodeling of isolated arterioles with myogenic tone.
AB  - Norepinephrine (NE, 10(-5.5) M) exposure for 4 h induces tone augmentation and
      vasodilation impairment after its removal. These changes are believed to
      represent early stages of inward remodeling. The hypothesis was tested that
      adrenoceptors causing vasoconstriction are responsible for NE-induced maintenance
      of augmented tone and vasodilation impairment, and that other vasoconstrictors
      associated with in vivo inward remodeling, a condition in which the internal
      passive diameter of arterioles is reduced without changes in medial cross
      sectional area, also induce these changes in isolated arterioles. alpha
      Adrenoceptor blockade prevented tone augmentation and vasodilation impairment,
      while beta-adrenoceptor blockade allowed NE to induce those changes plus inward
      remodeling. Endothelin-1 (10(-8) M) induced tone augmentation and vasodilation
      impairment. Angiotensin II (ANG-II, 10(-7) M) and platelet-derived growth factor
      (10 ng/ml) did not. ANG-II did not cause sustained vasoconstriction, but induced
      inward remodeling dependent on presence of myogenic tone and tyrosine
      phosphorylation. Thus, prolonged vasoconstriction is not required during ANG-II
      induced inward remodeling, suggesting remodeling processes effected by different
      agonists vary, with tone augmentation and impaired vasodilation occurring when
      vasoconstriction is required. This stresses the dynamic structure of arterioles,
      with rapid remodeling possibly involving functional changes and changes in
      extracellular matrix, cellular attachments, and/or cytoskeletal structures.

PMID- 18087169
TI  - Oral vitamin C administration increases lipid peroxidation in hemodialysis
      patients.
AB  - BACKGROUND: Since vitamin C (ascorbic acid, AA) deficiency is common in
      hemodialysis patients, systematic supplementation has been recommended. Further,
      vitamin C has been advocated as a potential adjuvant to erythropoietin by virtue
      of its capacity to improve iron utilization. However, vitamin C may have a
      paradoxical pro-oxidant effect in the presence of iron. METHODS: In 109
      hemodialysis patients, oral vitamin C was administered at 360 and 1,500 mg/week
      during 3 months each, followed by a wash-out period of 3 months. RESULTS: Serum
      AA increased from 0.22 to 0.33 and 0.63 mg/dl after 360 and 1,500 mg/week,
      respectively. However, a commensurate increase of plasma malondialdehyde (MDA), a
      parameter of lipid peroxidation, with 9 and 26% was observed. Serum AA and plasma
      MDA returned to baseline after withdrawal of vitamin C. Parameters of iron
      status, nutrition, inflammation, dialysis efficiency and plasma lipids remained
      unaltered. In a stepwise multiple regression analysis, serum AA and ferritin were
      strong and independent predictors of MDA. CONCLUSION: Oral vitamin C
      supplementation in hemodialysis patients increases lipid peroxidation, especially
      in patients with increased serum ferritin. The potential benefits of restored
      vitamin C status and improved erythropoiesis may be entirely overruled by the
      adverse consequences of oxidative tissue injury.

PMID- 18087170
TI  - Serum high-sensitivity C-reactive protein is not increased in patients with IgA
      nephropathy.
AB  - BACKGROUND/AIMS: The development of renal injury in glomerulonephritis (GN) has
      been related to systemic inflammatory mediators. We investigated whether serum
      high-sensitivity C-reactive protein (hs-CRP) is a marker reflecting the
      inflammatory pathogenesis of primary GN. METHODS: We compared serum hs-CRP levels
      in 192 patients with IgA nephropathy (IgAN), 43 patients with membranous
      nephropathy (MN), and 25 patients with minimal change disease (MCD) undergoing
      kidney biopsy and 638 matched controls. RESULTS: There were no differences in hs
      CRP levels between controls (median 0.08 mg/dl; range 0.03-1.87 mg/dl) and
      patients with IgAN (0.08 mg/dl; 0.03-3.13 mg/dl), MN (0.07 mg/dl; 0.03-0.99
      mg/dl) or MCD (0.08 mg/dl; 0.03-1.75 mg/dl). In patients with IgAN, hs-CRP levels
      did not differ according to Haas' pathological subclasses or subsequent renal
      outcomes. In the IgAN group, hs-CRP showed positive correlations with IgA, uric
      acid, systolic blood pressure, BMI and age. Hs-CRP level was significantly higher
      in male than in female IgAN patients. Serum IgA concentration was the strongest
      independent correlate with hs-CRP levels, and gender and BMI were also
      independently associated with hs-CRP. There were no correlations between hs-CRP
      and markers of disease activity. CONCLUSION: It is likely that hs-CRP does not
      closely reflect inflammatory pathogenesis in patients with IgAN, MN and MCD.

PMID- 18087171
TI  - rHuEPO dose inversely correlated with the number of circulating CD34+ cells in
      maintenance hemodialysis patients.
AB  - BACKGROUND: A decreased number of endothelial progenitor cells (EPCs) as well as
      anemia have been reported to be associated with cardiovascular disease.
      Maintenance hemodialysis (MHD) patients who require higher doses of recombinant
      human erythropoietin (rHuEPO) have higher cardiovascular mortality. However, it
      has not been examined whether there is correlation between the numbers of CD34+
      cells, including EPCs and erythroid progenitor cells, and the dose of rHuEPO in
      MHD patients. METHODS: We measured the number of circulating CD34+ cells by flow
      cytometry and examined the clinical characteristics in 35 MHD patients (50%
      male). RESULTS: A significant negative correlation was discovered between the
      number of circulating CD34+ cells and the dose of rHuEPO (r = -0.441, p = 0.013).
      We performed multivariate regression analysis to determine whether the number of
      CD34+ cells was associated with age, gender, diabetes, serum albumin, C-reactive
      protein, ferritin, statin, and dose of rHuEPO. The dose of rHuEPO, diabetes, and
      statin were independent predictors of the number of circulating CD34+ cells. A
      reciprocal analysis that divided these patients into two groups according to mean
      value of CD34+ cells also demonstrated the significant relationship between
      rHuEPO dose level and the number of CD34+ cells. CONCLUSION: These findings
      suggested that the requirement of a higher dose of rHuEPO to maintain target
      hemoglobin was associated with a decrease in the number of CD34+ cells. This
      relationship may be partly responsible for the higher cardiovascular mortality of
      this group among MHD patients.

PMID- 18087172
TI  - Evidence for increased risk of prediabetes in the uremic patient.
AB  - A prediabetic state is defined as a higher than normal blood glucose level but
      not yet high enough to meet the diagnosis of overt diabetes mellitus. While
      patients with advanced diabetic nephropathy are vulnerable to hypoglycemia, we
      believe that there is sufficient evidence that uremic nondiabetic patients are
      susceptible to hyperglycemia, which calls for more attention that uremia is a
      prediabetic state. It is, therefore, intriguing to identify these uremic factors
      which lead to prediabetes. Such a study may have significance to improve uremic
      patients' outcomes. To raise the awareness of the uremic prediabetic state, this
      review will, therefore, elaborate on the analysis of factors important in the
      development of prediabetes in uremia and will delineate whether their
      modification leads to an improved patient outcome.

PMID- 18087173
TI  - Stem cell factor in a rat model of serum nephrotoxic nephritis.
AB  - BACKGROUND: Stem cell factor (SCF) has been implicated in many disease processes
      characterized by tissue remodelling and fibrosis. The growth factor (SCF) was
      evaluated in a rat model of nephrotoxic serum nephritis (NTN), characterized by
      early inflammation followed by later tissue fibrosis. METHODS: NTN was induced in
      male Wistar Kyoto rats using rabbit anti-rat glomerular basement membrane
      antibodies. Animals were sacrificed at days 7, 15, 30 and 45 (n = 4-10 per
      group). Rats' kidneys were immunostained for ED1 as marker of inflammation, CD34,
      SCF, c-kit, mast cell tryptase and markers of fibrosis; collagens III and IV and
      alpha-SMA. Changes in SCF protein and mRNA content were evaluated by Western
      blotting and Northern blotting, respectively. RESULTS: In the NTN kidney, levels
      of immunoreactive SCF and SCF receptor (c-kit) were significantly higher in
      glomerular, tubular and interstitial compartments. Mast cells were barely
      detectable in NTN and control rat sections. Double immunostaining showed the co
      localization of SCF with alpha-SMA and of the SCF receptor with CD34 and ED1
      positive cells. Immunostainable SCF protein in each of the 3 compartments,
      glomerular, tubular and interstitial, showed a positive linear correlation with
      serum creatinine, proteinuria, glomerulosclerosis score and interstitial fibrosis
      scores. Using multivariate analysis, immunostainable tubular SCF was a predictor
      of glomerular sclerosis and immunostainable glomerular SCF predicted tubular
      atrophy. Increased SCF immunostain was not a consequence of altered transcription
      as there was a fall in SCF mRNA determined by Northern blotting. Western blotting
      of NTN kidney homogenates revealed two bands for SCF, a 43-kDa band which
      decreased, and a 19-kDa band which increased throughout the study. CONCLUSION:
      These results highlight the potential role of SCF and its receptor in the
      remodelling process of the NTN kidney. Upregulation of SCF may involve a
      translational mechanism, with the soluble SCF protein KL-S1 (19 kDa) being
      derived from the transmembrane SCF protein KL-1 (43 kD) by proteolytic cleavage.
      The immunohistochemical staining of few CD34+ cells in NTN kidneys warrants
      further evaluation of the nature of these cells in the context of the
      inflammatory as well as the fibrotic processes.

PMID- 18087174
TI  - Use of systemic antineoplastic drug therapy after regulatory agency approval.

PMID- 18087175
TI  - Pegylated liposomal doxorubicin (caelyx) in metastatic breast cancer: a community
      based observation study.
AB  - OBJECTIVES: Pegylated liposomal doxorubicin (PLD) has improved therapy options
      significantly, as it causes less myelosuppression, nausea, vomiting, and alopecia
      than conventional doxorubicin, while maintaining efficacy. The goal of this
      survey was to determine whether the use of PLD in a community-based patient group
      is comparable regarding chemotherapeutic doses and side effects to preselected
      study patients. METHODS: 100 questionnaires were randomly sent to Swiss
      oncologists in private practices, general hospitals and university hospitals.
      RESULTS: The patient cohort was heterogeneous with respect to prior treatments.
      PLD was an active agent in metastatic breast cancer and was well tolerated by the
      majority of patients. The most common non-hematological side effects were hand
      foot syndrome (HFS) and mucositis while only patients receiving a dose of 50
      mg/m(2) (recommended dose) experienced grade 4 HFS. The reported mean dose of PLD
      was 38.5 mg/m(2). CONCLUSIONS: This community-based observational study supports
      previous reports indicating that PLD at a median dose of < or =40 mg/m(2) every 4
      weeks is an active, well-tolerated agent in non-selected, pretreated patients
      with metastatic breast cancer.

PMID- 18087176
TI  - The 90-year anniversary of Katsusaburo Yamagiwa's carcinogenesis. Proceedings of
      the 1st International Awaji Liver Symposium. December 1, 2005. Awaji Island,
      Japan.

PMID- 18087177
TI  - Management of hepatocellular carcinoma in Japan: consensus-based clinical
      practice manual proposed by the Japan Society of Hepatology.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death not
      only in Japan but worldwide. Clinical Practice Guidelines for HCC were published
      in 2001 by the European Society of Study of the Liver (EASL) and in 2005 by the
      American Association for the Study of Liver Disease (AASLD). However, these
      guidelines have proven to be somewhat unsuitable for Japanese patients. In 2005,
      supported by the Japanese Ministry of Health, Labor and Welfare, Evidence-Based
      Clinical Practice Guidelines for HCC were compiled. Based on 'evidence-based'
      guidelines and the consensus of an expert panel on HCC, the Japan Society of
      Hepatology (JSH) published the Consensus-Based Clinical Practice Manual in 2007.
      In this article, the content of this manual, especially issues on surveillance,
      diagnosis, staging, and treatment, is summarized.

PMID- 18087178
TI  - Long-term effects of interferon-based therapy for chronic hepatitis C.
AB  - Hepatitis C virus infection frequently causes chronic liver disease leading to
      cirrhosis and hepatocellular carcinoma (HCC) and has become the main indication
      for liver transplantation. Interferon (IFN)-based therapy has been used in the
      treatment of chronic hepatitis C (CHC) for viral clearance. Several earlier
      studies showed long-term beneficial effects of IFN monotherapy in reducing the
      progression of cirrhosis, hindering HCC development, and prolonging survival
      among both sustained virological responders and nonresponders. However, the
      benefits of preventing disease progression in CHC patients without sustained
      virological response (SVR) no longer existed over a longer observation period.
      Both IFN monotherapy and IFN-ribavirin combination therapy were shown to reduce
      significantly the complications of liver disease, in terms of development of
      cirrhosis, HCC and liver-related mortality. The significance disappeared after
      response to antiviral treatment was taken into account. The benefits were
      obtained mainly from successful antiviral treatment but were not related to the
      antiviral regimens, suggesting that the magnitude of this preventive effect could
      increase through the significant improvement of SVR rate by using a more
      effective regimen, such as interferon-ribavirin or peginterferon-ribavirin
      combination therapy. Nevertheless, about one-third of patients remain resistant
      to the current recommended antiviral regimens. More effective treatment is needed
      for the population.

PMID- 18087179
TI  - Natural course of small nodular lesions with intranodular preserved portal supply
      in cirrhotic liver.
AB  - BACKGROUND AND AIM: Due to recent advances in imaging technology, small nodules
      or lesions in cirrhotic liver are now seen easily. Intranodular blood supply is
      useful in characterizing these nodules. However, nodules with preserved portal
      blood supply may be malignant or benign, and it is unknown how often these
      nodules develop into overt hepatocellular carcinoma (HCC). This study was
      performed to clarify the rate of malignant transformation in such lesions with
      preserved portal perfusion in cirrhotic liver. METHODS: From 1995 to 1997, in 98
      patients, we performed CT during arterial portography and ultrasound angiography
      with intra-arterial CO2 injection for 113 nodules <3 cm in diameter to determine
      the intranodular blood supply. Of these, 48 nodules in 36 patients were diagnosed
      as 'benign nature nodules' on the basis of the blood supply of the nodules, which
      included arterial hypovascularity with preserved portal supply. Percutaneous
      biopsy of the nodule was undertaken for all nodules for histopathologic
      diagnosis. Thirty-two nodules in 22 patients that were not diagnosed as early HCC
      were followed-up clinically without any treatment to clarify the natural course
      of the nodules. RESULTS: Twelve nodules in 14 patients did not increase in size
      and no new nodules appeared in any part of the liver. Ten nodules in 7 patients
      did not increase in size or arterial vascularity but typical overt HCC appeared
      in other areas of the liver. Only two nodules in 2 patients increased in size and
      developed into hypervascular overt HCC during the 15- and 34-month observation
      periods, respectively. CONCLUSION: Nodules with preserved portal perfusion in
      cirrhotic liver have a low risk of malignant transformation compared with the
      surrounding liver parenchyma.

PMID- 18087180
TI  - From molecular biology to targeted therapies for hepatocellular carcinoma: the
      future is now.
AB  - Hepatocellular carcinoma (HCC) is characterized as a highly chemoresistant cancer
      with no effective systemic therapy. Despite surgical or locoregional therapies,
      prognosis remains poor because of high tumor recurrence or tumor progression, and
      currently there are no well-established effective adjuvant therapies. The
      molecular biology of carcinogenesis and tumor progression of HCC has been
      increasingly understood with intense research in recent years. Several important
      intracellular signaling pathways such as the Ras/Raf/Mek/Erk pathway and
      PI3k/Akt/mTOR pathway have been recognized, and the role of several growth
      factors and angiogenic factors such as EGF and VEGF has been confirmed. Effective
      agents targeting these molecular abnormalities have been developed and widely
      tested in preclinical studies of HCC cell lines or xenograft models. Several
      agents have entered clinical trials in HCC patients, and recent data indicated
      that a multikinase inhibitor targeting Ras kinase and VEGFR-2, sorafenib, is
      effective in prolonging survival of patients with advanced HCC. The management of
      advanced HCC is entering the era of molecular targeting therapy, which is of
      particular significance for HCC in view of the lack of existing effective
      systemic therapy for this cancer.

PMID- 18087181
TI  - Development of a novel assay to quantify serum human telomerase reverse
      transcriptase messenger RNA and its significance as a tumor marker for
      hepatocellular carcinoma.
AB  - Currently available tumor markers for hepatocellular carcinoma (HCC) are alpha
      fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and Des-gamma
      carboxy prothrombin (DCP). However, their positive rate can not surpass abdominal
      ultrasonography (US) as modalities to detect small HCC at early stage, resulting
      in a possible delay of its diagnosis. There is a need to develop an additional
      sensitive marker to improve the early detection of HCC. We here introduced a
      newly developed quantitative detection method for serum hTERT mRNA, which has a
      clinical significance in HCC diagnosis. Briefly, we examined its sensitivity and
      specificity in HCC diagnosis, clinical significance in comparison with other
      tumor markers, and its correlations with the clinical parameters. Serum hTERT
      mRNA showed higher values in patients with HCC than those with chronic liver
      diseases. hTERT mRNA expression independently correlated with clinical parameters
      such as differentiation degree (p < 0.001). The sensitivity/specificity of hTERT
      mRNA in HCC diagnosis showed 88.2/70.0%. hTERT mRNA proved to be expectedly
      superior to AFP mRNA , AFP and DCP in HCC diagnosis. Importantly, hTERT mRNA in
      serum correlated with that in HCC tissue. Thus, we report that serum hTERT mRNA
      is a novel and available marker for HCC diagnosis.

PMID- 18087182
TI  - PIVKA-II is a useful tumor marker for recurrent hepatocellular carcinoma after
      surgical resection.
AB  - OBJECTIVES: The aim of this study is to assess the usefulness of prothrombin
      induced by vitamin K absence or antagonist-II (PIVKA-II) in monitoring of
      recurrent hepatocellular carcinoma (HCC) after curative resection. METHODS: From
      April 2001 to March 2004, a total of 245 patients with histologically proven HCC
      and 267 non-HCC patients were recruited. Serial follow-up measurements of both
      alpha-fetoprotein (AFP) and PIVKA-II were performed in 27 patients who had
      recurrent HCC after resection. RESULTS: In the initial HCC diagnosis, the
      sensitivity of AFP and PIVKA-II was 48.6% (119/245) and 75.1% (184/245),
      respectively, at the cutoff of 20 ng/ml for AFP and 40 mAU/ml for PIVKA-II (p <
      0.01). The specificity was 81.3% (217/267) and 94.8% (253/267), respectively.
      When AFP and PIVKA-II were combined, the sensitivity and specificity was 83.3%
      (204/245) and 77.2% (206/267), respectively. In 27 patients developing recurrent
      HCC after curative surgical resection, the sensitivity of AFP and PIVKA-II was
      40.7% (11/27) and 74.1% (20/27), respectively. Several fluctuating patterns of
      AFP and PIVKA-II were observed from initial diagnosis to recurrence. CONCLUSION:
      Our data suggest that PIVKA-II is a useful tumor marker for HCC, complementary to
      AFP. Serial measurements of both markers after resection might be helpful for
      early diagnosis of tumor recurrence.

PMID- 18087183
TI  - Superiority of CT arterioportal angiography to contrast-enhanced CT and MRI in
      the diagnosis of hepatocellular carcinoma in nodules smaller than 2 cm.
AB  - To evaluate the effectiveness of computed tomography (CT) arterioportal
      angiography in the diagnosis of hepatocellular carcinoma (HCC) in nodules smaller
      than 2 cm, we compared the findings of CT during arteriography (CTA) and CT
      during arterial portography (CTAP) with those of enhanced CT and enhanced
      magnetic resonance imaging (MRI). Sixty-eight nodules smaller than 2 cm in 53
      patients with liver cirrhosis were classified into three groups of CTA and CTAP:
      (group 1) hyperattenuation on CTA, and hypoattenuation on CTAP (56 nodules, 41
      patients); (group 2) hypoattenuation on CTA, and hypoattenuation on CTAP (10
      nodules, 10 patients); (group 3) hypoattenuation on CTA, and hyperattenuation on
      CTAP (2 nodules, 2 patients). Histologically, 96% (54/56), 80% (8/10), and 100%
      (2/2) of the nodules in groups 1, 2 and 3, respectively, were diagnosed as HCC.
      In group 1, enhanced CT or enhanced MRI confirmed hypervascularity in only 77%
      (30/39) and venous washout in 21% (8/39). In groups 2 and 3, enhanced CT or
      enhanced MRI on 7 and 2 nodules, respectively, revealed no hypervascularity (0%).
      The results suggested that CT arterioportal angiography is superior to enhanced
      CT and MRI in nodules smaller than 2 cm for diagnosing HCC (p < 0.01 group 1, p <
      0.01 group 2).

PMID- 18087184
TI  - Efficacy and tolerability of low-dose thalidomide as first-line systemic
      treatment of patients with advanced hepatocellular carcinoma.
AB  - OBJECTIVE: The systemic treatment of advanced hepatocellular carcinoma (HCC) has
      produced disappointing results thus far. HCC is a hypervascular tumor with over
      expression of angiogenic factors such as vascular endothelial growth factor.
      Thalidomide is an anti-neoplastic agent with anti-angiogenic and other mechanisms
      of action. We aim to evaluate the efficacy and toxicity of low-dose (100 mg)
      thalidomide as the first-line treatment of advanced HCC. METHODS: Between August
      2003 and March 2007, 45 patients who had received thalidomide 100 mg daily as
      first-line treatment of advanced HCC were reviewed retrospectively. Advanced HCC
      was defined as either metastatic or not amenable to surgical or locoregional
      therapies. Diagnosis of HCC was based on clinical, biochemical and radiological
      grounds. Survival was analyzed by the Kaplan-Meier method. RESULTS: Thirty-eight
      patients were evaluable for response and toxicity. Two (5%) patients had partial
      response and 8 (21%) had stable disease. The overall median survival of patients
      in this cohort was 3.2 months (95% CI: 2.8-3.7 months). The common toxicities
      were somnolence (13%), peripheral neuropathy (11%) and ankle edema (8%), with no
      grade 3 or 4 toxicities and treatment-related deaths. CONCLUSION: Our study shows
      that a single agent, low-dose thalidomide has a modest clinical activity with
      good tolerability in treating advanced HCC patients.

PMID- 18087185
TI  - Severe complications of radiofrequency ablation therapy for hepatocellular
      carcinoma: an analysis of 3,891 ablations in 2,614 patients.
AB  - OBJECTIVE: To clarify information on and frequency of complications as well as
      mortality rate after radiofrequency ablation (RFA) for hepatocellular carcinoma.
      METHODS: The results of a questionnaire obtained mainly from members of the Osaka
      Liver Cancer Study Group at 43 departments of 38 facilities were analyzed in
      order to clarify the current status of RFA, and information on and frequency of
      complications and death occurring after RFA. RESULTS: Between January 1999 and
      May 2002, a total of 3,891 RFA therapies were performed percutaneously in 2,542
      patients, laparoscopically in 23, and operatively in 49 (2,614 patients in
      total). Complications were observed in 207 of 2,614 patients (7.9%), and 9 (0.3%)
      died within 3 months after RFA. Among these 9 nonsurvivors, 3 had liver failure,
      3 rapid progression and sarcomatous changes, 1 biliary injury, 1 gastrointestinal
      bleeding, and 1 acute myocardial infarction. The departments that treated larger
      numbers of patients per month had a smaller number of complications and deaths.
      CONCLUSION: It is possible that complications of RFA can be reduced by gathering
      experience.

PMID- 18087186
TI  - Treatment of hepatocellular carcinoma using internally cooled electrodes. A
      prospective comparison of modified automated vs. manual pulsed radiofrequency
      algorithms.
AB  - OBJECTIVES: To compare the effectiveness of modified automated and manual pulsed
      radiofrequency (RF) algorithms using internally cooled electrodes for
      hepatocellular carcinoma (HCC). METHODS: Seventy-seven treatment-naive cirrhotic
      patients with 102 HCC (< or =4 cm) underwent 109 sessions of ultrasound-guided
      percutaneous RF ablation using a 17-gauge, 20-cm-long, single internally cooled
      electrode. Patients were assigned alternatively: 40 patients to the modified
      automated algorithm group and 37 patients to the manual algorithm group. The mean
      tumor diameters were 2.34 +/- 0.9 and 2.25 +/- 0.7 cm in the automated and manual
      groups, respectively (p = 0.56). Primary technique effectiveness and local tumor
      progression were compared between the two groups. RESULTS: More overlapping
      ablations (n = 112) were required in the manual than in the automated group (n =
      82) to achieve similar primary technique effectiveness rates of 96.1 and 94.1%,
      respectively. After a mean follow-up period of 26.7 +/- 1.1 months, the local
      tumor progression rates at 12 and 18 months were 4 and 20% in the manual group
      and 12 and 24% in the modified automated group (p = 0.3). Only tumors >3 cm were
      independently associated with local tumor progression (odds ratio 1.25; 95% CI
      1.06-2.34, p = 0.03). CONCLUSIONS: The manual algorithm requires more overlapping
      ablations and treatment sessions in order to achieve similar primary technique
      effectiveness and local tumor progression rates compared with the modified
      automated algorithm.

PMID- 18087187
TI  - CT Imaging of early hepatocellular carcinoma and the natural outcome of
      hypoattenuating nodular lesions in chronic liver disease.
AB  - BACKGROUND: The Liver Cancer Study Group of Japan has designated early
      hepatocellular carcinoma (HCC) a clinically early-stage HCC corresponding to a
      high-grade dysplastic nodule as proposed by the International Working Party.
      METHODS: The majority of resected early HCCs were demonstrated as having hypo- or
      isoattenuation in the arterial and delayed phases of dynamic CT. RESULTS: Only 5%
      of early HCCs were hyperattenuated on dynamic CT, whereas 94% of advanced small
      HCC were hyperattenuated. CT arterial portography (CTAP) showed that 66% of early
      HCCs were hypo- and 34% were isoattenuated. CT hepatic arteriography (CTHA)
      demonstrated that 55% of them were hypo-, 30% were iso- and the remaining 15%
      were hyperattenuated. CONCLUSIONS: These findings suggest that most early HCCs
      receive equal or decreased blood supply from both portal and arterial blood flow
      compared with surrounding hepatic parenchyma. In contrast, 97% of small advanced
      HCCs were hypoattenuated on CTAP, and 93% were hyperattenuated on CTHA. For
      nodule-in-nodule type HCC, the central portion of the lesion was hyperattenuating
      and the peripheral portion was hypoattenuating in the arterial phase of dynamic
      CT, and both areas became hypoattenuated in the delayed phase. Sixty
      hypoattenuating nodular lesions in chronic liver disease were followed
      periodically with helical CT. Thirty-six (60%) of them developed to the
      hyperattenuating type (attenuation conversion), 21 were unchanged, and 3
      disappeared spontaneously. The hyper-in-hypo-attenuating lesions showed rapid
      progression to entirely enhanced lesions, i.e. overt HCC. Dynamic CT is
      recommended as one of the low-invasive imaging modalities to follow the
      hypoattenuating nodules and to determine the optimal treatment with careful
      attention being given to intratumoral attenuation conversion.

PMID- 18087188
TI  - What is the best time to evaluate treatment response after radiofrequency
      ablation of hepatocellular carcinoma using contrast-enhanced sonography?
AB  - PURPOSE: To observe the visibility and changes in the echogenicity of ablated
      tumor and ablated nontumor areas after radiofrequency ablation (RFA) over time
      using gray-scale sonography, and, consequently, to decide on the best timing for
      contrast-enhanced sonography to evaluate the response of hepatocellular carcinoma
      to RFA. MATERIALS AND METHODS: Thirty-eight patients with 48 hepatocellular
      carcinoma nodules underwent RFA. Consecutive gray-scale sonographic observations
      were made 10 min before RFA and at five points within 4 days after RFA. Two
      hepatologists blindly reviewed the sonographic images to assess the
      identifiability of the boundary of the ablated nodules and to semiquantitatively
      score the echogenicity of the ablated tumor and ablated nontumor regions in 15
      hypoechoic nodules with detectable boundaries within 4 days after RFA. RESULTS:
      The detection rates of the boundaries of ablated tumors were 56.5, 65.2, 54.3,
      43.5, and 39.1% at 3-6 h and 15-22 h and on the 3rd, 4th, and 5th days after RFA.
      There was a significant difference between the detection rate for ablated tumors
      at 15-22 h and that on the 3rd and 4th days. The difference in echogenicity
      between ablated tumor and ablated nontumor tissue reached a maximum at 15-22 h
      after RFA. CONCLUSION: Ablated tumor can be clearly identified within the ablated
      area in 65.2% of cases using gray-scale sonography at 15-22 h after RFA. The day
      following RFA is most appropriate and practical for the performance of contrast
      enhanced sonography to evaluate the therapeutic response, including a safety
      margin.

PMID- 18087189
TI  - Initial treatment response is essential to improve survival in patients with
      hepatocellular carcinoma who underwent curative radiofrequency ablation therapy.
AB  - OBJECTIVE: This study was undertaken to assess the outcome of potentially
      curative radiofrequency ablation (RFA) therapy for early-stage hepatocellular
      carcinoma (HCC) in patients with Child-Pugh stage A cirrhosis. METHODS: This
      study retrospectively evaluated clinical outcomes in a cohort of 171 Child-Pugh
      stage A cirrhotic patients who received RFA for naive HCC within the Milan
      criteria. The median follow-up period was 36.7 months. RESULTS: Cumulative
      survival rates estimated by the Kaplan-Meier method for all patients were 98.8,
      91.1 and 76.8% at 1, 3 and 5 years, respectively. Cumulative probabilities of
      local tumor recurrence at 1, 2 and 3 years were 9.0, 14.1 and 17.7%,
      respectively. Cumulative survival rates in patients without local tumor
      recurrence were 96.6, 94.6 and 84.4% at 1, 3 and 5 years, respectively, compared
      with patients with local tumor recurrence (96.6, 74.8 and 42.1% at 1, 3 and 5
      years, respectively; p = 0.0002). Cox regression analysis showed that low serum
      albumin (p = 0.009, RR 3.04, CI 1.32-6.98), high range of PIVKA-II (prothrombin
      induced by vitamin K absence or agonist II) (p = 0.025, RR 2.57, CI 1.13-5.89),
      with multiple (less than 3) nodules (p = 0.021, RR 2.61, CI 1.15-5.91), and with
      local tumor recurrence (p = 0.004, RR 3.62, CI 1.51-8.69) were significant risk
      factors for death. CONCLUSION: Initial complete response of curative RFA therapy
      in patients with Child-Pugh stage A cirrhosis and early-stage HCC is associated
      with improved survival. Therefore, clinicians should aim to achieve complete
      ablation of all detectable HCC nodules with adequate safety margins.

PMID- 18087190
TI  - Role of 18F-fluorodeoxyglucose positron emission tomography in detecting
      extrahepatic metastasis in pretreatment staging of hepatocellular carcinoma.
AB  - OBJECTIVES: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is
      useful for differentiating benign from malignant lesions, evaluating tumor stage,
      monitoring the response to therapy and detecting tumor recurrence in a variety of
      malignancies. Nevertheless, its use in patients with hepatocellular carcinoma
      (HCC) is still uncertain. We evaluated whether FDG-PET has a role in detecting
      extrahepatic metastasis in pretreatment tumor staging of HCC and the
      characteristics of patients with extrahepatic metastasis that benefit from FDG
      PET. METHODS: Eighty-seven patients with HCC underwent computed tomography (CT)
      or magnetic resonance imaging (MRI) of the abdomen and chest X-ray to evaluate
      pretreatment tumor staging. FDG-PET was then performed to detect extrahepatic
      metastasis. The power of FDG-PET to detect extrahepatic metastasis was compared
      with that of conventional images. In addition, we evaluated whether the detection
      of extrahepatic metastasis using FDG-PET changed the TNM stage. Moreover, we
      investigated the clinical and tumor characteristics of patients with extrahepatic
      HCC metastasis. RESULTS: Extrahepatic metastases were identified in 24 of 87
      patients. The location and frequency of metastases were lung 12, lymph nodes 19
      and bone 11. All of the extrahepatic metastases were detected by FDG-PET. In
      addition, FDG-PET identified 4 lymph node metastases and 6 bone metastases that
      were not found using conventional methods. The initial TNM stage based on the
      conventional staging workup was changed in 4 cases after FDG-PET. Extrahepatic
      metastasis was significantly more frequent in patients with intrahepatic tumor >5
      cm in size (p = 0.045). CONCLUSIONS: FDG-PET is a useful imaging modality for
      identifying extrahepatic metastases which may lead to accurate staging and proper
      management of patients with possible extrahepatic metastases.

PMID- 18087191
TI  - Percutaneous radiofrequency ablation of sonographically unidentifiable liver
      tumors. Feasibility and usefulness of a novel guiding technique with an
      integrated system of computed tomography and sonographic images.
AB  - OBJECTIVE: The purpose of this study was to evaluate the safety and feasibility
      of a real-time integrated system with computed tomography (CT) and sonographic
      images for radiofrequency (RF) ablation of hepatic malignancies poorly defined on
      B-mode sonography, and to clarify the suitable phase of CT images for using this
      virtual sonography. METHODS: Between September 2004 and December 2004, 12
      patients with 16 hepatocellular carcinomas and two metastatic lesions arising
      from colorectal adenocarcinoma (n = 1) and rectal carcinoid (n = 1) were treated.
      The maximum diameter of nodules ranged from 1.0 to 2.5 cm (mean +/- SD; 1.5 +/-
      0.6 cm) on CT images. RESULTS: Complete tumor necrosis was achieved in a single
      session in 19 lesions (90%), while a second session was required for the
      remaining two lesions (10%). Portal phase multi-planar reconstruction images were
      displayed under a suitable position corresponding to the ultrasound images in 9
      patients (HCC = 7, metastasis = 2), and arterial phase multi-planar
      reconstruction images were displayed in the 3 remaining patients with
      hepatocellular carcinoma. CONCLUSION: Percutaneous RF ablation guidance using
      virtual sonography is an effective treatment for patients with hepatic
      malignancies. The portal phase of CT images may be the most suitable to indicate
      the 3-dimensional relationship between the liver vasculature and tumors on
      virtual sonography.

PMID- 18087192
TI  - Evaluating patients with cirrhosis for hepatocellular carcinoma: value of
      clinical symptomatology, imaging and alpha-fetoprotein.
AB  - OBJECTIVE: This study was undertaken to assess the value of clinical
      symptomatology, abdominal ultrasound (US), triple-phase CT (TPCT) and serum alpha
      fetoprotein (AFP) estimation in predicting presence of hepatocellular carcinoma
      (HCC) among patients with cirrhosis. MATERIALS AND METHODS: In this cross
      sectional study, Child's A/B cirrhosis patients were subjected to clinical
      evaluation, US, TPCT and serum AFP estimation. Sensitivity and specificity of
      clinical symptoms and of AFP at different cut-off levels were determined.
      Detection rate of HCC and agreement between US and TPCT was estimated. RESULTS: A
      high proportion of enrolled subjects had HCC at first presentation (40.7%).
      Significantly higher prevalence of abdominal pain, weight loss, and anorexia was
      seen in patients with cirrhosis with HCC compared to those without HCC.
      Sensitivity and specificity of any of these symptoms was 73 and 79%, respectively
      (positive and negative predictive values of 65 and 85%, respectively). A 100%
      agreement between TPCT and US was observed for diagnosing HCC cases. However,
      TPCT detected a greater number of smaller HCCs. Sensitivity of AFP at 400 ng/ml
      cut-off was only 25.7%, too low to be useful. Best mix of sensitivity (77.2%) and
      specificity (78.1%) of AFP was found to be at 10.7 ng/ml cut-off which falls
      within the conventional limits of normalcy. CONCLUSION: The study highlights the
      importance of symptomatology of weight loss, abdominal pain or anorexia as
      markers for HCC in patients with cirrhosis. AFP was not found to be a useful
      screening test. TPCT should be undertaken in all cirrhotics presenting to the
      hospital for the first time.

PMID- 18087193
TI  - Microwave ablation of hepatocellular carcinoma.
AB  - OBJECTIVE: This article reviews the basic principles, equipment, current
      therapeutic status and future trends of microwave ablation (MWA) in the treatment
      of hepatocellular carcinoma (HCC). METHODS: All articles published in English on
      MWA or MWA as a treatment for HCC were identified with a PubMed search from the
      1990s through June 2007. Papers were reviewed on the technical advances of MWA
      equipment and the clinical applications of MWA including indications, techniques,
      therapeutic outcomes, complications and combination therapies. RESULTS: MWA has
      several advantages, including high thermal efficiency, higher capability of
      coagulating blood vessels, faster ablation time, and an improved convention
      profile. MWA can induce large ablation volumes and yield good local tumor
      control, especially for small HCC. Larger HCC can also be completely ablated by
      using more effective antenna or simultaneous application of multiple antennae.
      Long-term survival comparable to that of surgery was obtained for tumors
      measuring 4 cm or less. Associated complications appear to be low. CONCLUSIONS:
      MWA is a promising minimally invasive technique for the treatment of HCC. Future
      advances are warranted to improve the therapeutic efficacy.

PMID- 18087194
TI  - Long-term interferon maintenance therapy improves survival in patients with HCV
      related hepatocellular carcinoma after curative radiofrequency ablation. A
      matched case-control study.
AB  - OBJECTIVE: To assess whether low-dose, long-term maintenance interferon (IFN)
      therapy inhibits recurrence after complete ablation of hepatocellular carcinoma
      (HCC) and improves patient survival. METHODS AND PATIENTS: From June 1999 through
      May 2006, a total of 127 HCC cases that met the requirements of both tumor
      diameter 3 cm or less, and number of tumors three or fewer, were curatively
      treated by radiofrequency ablation therapy (RFA). Among them, 43 patients
      received three million IU of IFN-alpha2b twice per week or pegylated IFN-alpha2a
      90 microg once per week or once per 2 weeks without discontinuation (IFN
      maintenance group). The remaining 84 patients, whose sex, age, and platelet
      counts were randomly matched to those of the IFN maintenance group, did not
      receive IFN treatment (control group). RESULTS: Cumulative first, second, and
      third recurrence rates were significantly reduced in the IFN maintenance group
      compared with the control group by Kaplan-Meier estimate. The 5-year survival
      rate was 66% for the control group and 83% for the IFN maintenance group (p =
      0.004). Multivariate analysis using the Cox proportional hazards model identified
      IFN maintenance therapy as an independent risk factor for survival, and the risk
      ratio was 0.21 (95% CI: 0.05-0.73). In conclusion, low-dose, long-term
      maintenance IFN therapy after curative RFA therapy of HCC significantly inhibits
      recurrence, and consequently improves patient survival.

PMID- 18087195
TI  - Associations between Notch-2, Akt-1 and HER2/neu expression in invasive human
      breast cancer: a tissue microarray immunophenotypic analysis on 98 patients.
AB  - OBJECTIVE: We aimed to investigate the existence of associations between well
      established and newly recognized biological and phenotypic features of breast
      cancer involved in tumor progression and prognosis. METHODS: Ninety-eight cases
      of invasive breast cancer were assessed for the immunohistochemical expression of
      estrogen and progesterone receptors, Ki-67, HER2, Akt-1, and Notch-2, using the
      tissue microarray technique. Data regarding tumor histotype, histological grade,
      tumor size and lymph node status were collected for each patient and included in
      the analysis. RESULTS: Several significant associations between histological
      and/or immunophenotypic features came from the analysis of our data. Positive
      associations were observed between estrogen and progesterone receptors, tumor
      grade and proliferation index, tumor grade and HER2, Akt-1 and estrogen
      receptors, and Notch-2 and HER2. Inverse associations were noted between hormone
      receptors and tumor grade, hormone receptors and HER2, Akt-1 and tumor grade, and
      Akt-1 and nodal invasion. CONCLUSIONS: Our results, showing the existence of a
      number of estrogen receptor-positive tumors with Akt-1 expression, better degree
      of differentiation, and no lymph node involvement, along with the presence of
      HER2-positive tumors with strong Notch-2 expression, support the role of Notch
      and Akt in breast cancer progression and suggest that they may also represent new
      appealing therapeutic targets.

PMID- 18087196
TI  - Male and female breast cancer--differences in DNA ploidy, p21 and p53 expression
      reinforce the possibility of distinct pathways of oncogenesis.
AB  - AIM: The purpose of this study was to compare the immunohistochemical profile of
      cell cycle inhibitors of G1/S phase transition (p21, p53 and pRb), Ki-67
      proliferation marker and DNA ploidy in male (MBC) and female breast cancer (FBC).
      MATERIAL AND METHODS: One hundred patients (50 non-consecutive cases of FBC and
      an equal number of MBC) were selected according to homogeneous features regarding
      age, histological type, tumour grading, nodal status and absence of neoadjuvant
      therapy. The expression of p21, p53, pRb and Ki-67 was assessed by
      immunohistochemistry, and DNA ploidy was analysed by flow cytometry. Correlations
      between variables were evaluated using the chi(2) test. RESULTS: The incidence of
      DNA aneuploid, p21-positive and p53-negative tumours was significantly higher in
      MBC than in FBC; pRb and Ki-67 revealed no statistically significant differences
      between the two entities. In MBC, high tumour grade correlated with aneuploidy,
      Ki-67 and pRb positivity; ploidy and p53 were also associated. In FBC, only
      ploidy and grade showed a strong correlation. CONCLUSION: The significant
      dissimilarities regarding DNA ploidy, p21 and p53 in these quite homogeneous
      groups of FBC and MBC point to different genomic instability and to differences
      in cell cycle proliferative control, reinforcing the view of somewhat distinct
      tumour oncogenesis.

PMID- 18087197
TI  - The lymphatic infiltration identified by D2-40 monoclonal antibody predicts lymph
      node metastasis in submucosal invasive colorectal cancer.
AB  - BACKGROUND AND STUDY AIMS: Lymphatic infiltration has been recognized as a
      significant risk factor for lymph node metastasis of submucosal invasive
      colorectal cancer (SICC), but it is difficult to detect microscopically on
      hematoxylin and eosin (H&E)-stained slides. We therefore identified lymphatic
      infiltration of tumor cells with D2-40 monoclonal antibody, which reacts
      specifically against the endothelium of lymphatic vessels, to make an objective
      and precise diagnosis. PATIENTS AND METHODS: The surgical specimens of 122
      consecutive patients with nonpedunculated SICC were examined for lymphatic
      infiltration by immunohistochemical staining with D2-40 monoclonal antibody (LI
      D) and for venous infiltration by Elastica van Gieson staining (VI-E). RESULTS:
      Lymph node metastasis was found in 20 patients. Multivariate analysis showed that
      LI-D (p = 0.0415) and VI-E (p = 0.0119) were significant risk factors for lymph
      node metastasis. Regardless of the presence of risk factors including at least
      either lymphatic infiltration or venous infiltration, no lymph node metastasis
      positive patients were found (0%) among the 25 patients whose colorectal cancer
      had a submucosal invasive depth of less than 1,500 microm. No lymph node
      metastasis was found in any of the patients with a depth of submucosal invasion
      of less than 3,000 microm, who had no risk factors, including LI-D or VI-E.
      CONCLUSIONS: Correct evaluation of lymphatic infiltration by immunohistochemical
      staining with D2-40 monoclonal antibody may play a crucial role in determining
      whether there are indications for additional treatment in the management of
      endoscopically resected SICC.

PMID- 18087198
TI  - Inducible nitric oxide synthase mediates hypoxia-induced hypoxia-inducible factor
      1 alpha activation and vascular endothelial growth factor expression in oxygen
      induced retinopathy.
AB  - OBJECTIVE: Previous studies provided evidence that many factors contribute to
      retinal angiogenesis, including inducible nitric oxide synthase (iNOS), hypoxia
      inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor
      (VEGF). But the role of nitric oxide generated by iNOS in the regulation of
      expression of hypoxia-inducible genes in retinopathy of prematurity remains
      unclear. So we sought to better define the molecular basis of this iNOS-dependent
      regulation. METHODS: In this study, using immunohistochemistry, real-time PCR and
      Western blotting technologies, we investigated the changes of iNOS, HIF-1 alpha,
      VEGF and phosphatidylinositol 3-kinase/Akt (PI3K/Akt) expressions. RESULTS:
      Hypoxia- induced overexpression of iNOS, HIF-1 alpha, VEGF, PI3K/Akt and
      phosphorylated PI3K/Akt was observed in the untreated retinopathy of the
      prematurity group. Administration of the selective iNOS inhibitor aminoguanidine
      hemisulfate markedly decreased the expression of these genes. CONCLUSIONS: These
      results indicate that iNOS mediates HIF-1 alpha activation and VEGF expression in
      retinal angiogenesis and that the PI3K/Akt signaling pathway may play a role in
      this process.

PMID- 18087199
TI  - DNA hypermethylation status of multiple genes in papillary thyroid carcinomas.
AB  - OBJECTIVE: The aim of this study was hypermethylation of multiple genes for
      papillary thyroid carcinomas (PTCs). METHODS: We examined 39 lesions using
      methylation-specific PCR to assess hypermethylation in genes, including
      p16(INK4a), p14(ARF), RB1, p27(Kip1)and 0(6)-MGMT. Homozygous deletions of
      p16(INK4a) and p14(ARF) were investigated by differential PCR, all with reference
      to clinicopathological factors. RESULTS: We found methylation of p16(INK4a) in
      35.9% (14/39); p14(ARF) in 2.6% (1/39); RB1 in 23.1% (9/39); p27(Kip1) in 15.4%
      (6/39),and 0(6)-MGMT in 15.4% (6/39). Hypermethylation of at least one of these
      genes was apparent in 66.7% (26/39). Homozygous deletions of p14(ARF) and
      p16(INK4a) were detected in 7.7 (3/39) and 2.6% (1/39), respectively. In cases
      with p16(INK4a) alterations, tumors were significantly increased. A history of
      chronic thyroid disease and lymphocytic infiltration was significantly associated
      with p14(ARF) alterations, without regional lymph node metastases. CONCLUSIONS:
      Our data suggest that alterations in p16(INK4a), mainly hypermethylation, may be
      linked to tumor growth but not tumor development, while alterations in p14(ARF)
      may contribute to the induction of chronic inflammation-related PTCs.

PMID- 18087201
TI  - The biopsychosocial model thirty years later.

PMID- 18087200
TI  - Anti-tumor effects of liposome-encapsulated titanium dioxide in nude mice.
AB  - Anatase particles of titanium dioxide (TiO2) absorb ultraviolet (UV) light which
      is shorter than 415 nm. Photoexcited TiO2, a strong oxidizer, is expected to
      inhibit malignant cell growth. Liposomes accelerate endophagocytosis to the
      cytoplasm of encapsulated materials. In this study, we examined anti-tumor
      effects of TiO2 and liposome-encapsulated TiO2 (LT) with UVA irradiation by an
      air pouch cancer model using NBT-II bladder cancer cells, which simulates bladder
      cancer. Injection of TiO2 or LT into the air pouch was followed by UVA
      irradiation via the opened pouch. Tumors of TiO2 + UVA and LT + UVA groups showed
      more pronounced necrotic areas, apoptotic indices, nitrotyrosine formation, tumor
      growth inhibition and increased survival compared with control groups. Especially
      the LT + UVA group showed more remarkable anti-tumoral effects than the TiO2 +
      UVA group, which was associated with higher TiO2 incorporation. These findings
      suggest that LT might be more effective than noncoated TiO2 in the treatment of
      bladder cancer.

PMID- 18087202
TI  - Gaps and limitations of psychological interventions for bipolar disorders.
AB  - OBJECTIVE: To highlight gaps or limitations in applying evidence-based
      psychological therapies as an adjunct to medication in the management of bipolar
      disorders. METHOD: General and specific gaps in knowledge or perceived
      limitations were determined by the authors and published examples were identified
      illustrating these potential barriers to the use or application of adjunctive
      therapies. RESULTS: Research on the benefits of psychological therapies in
      bipolar disorders has progressed dramatically in the last decade. There are some
      uncertainties that need to be further investigated. These can be broadly
      classified as: for whom should therapy be provided, what therapy and when should
      therapy be commenced. The latter can be seen from the perspective of both current
      mental state as well as length of history and number of recurrences. Other issues
      frequently highlighted by researchers in the field relate to mediators and
      moderators of therapy effects. CONCLUSION: Gaps in our knowledge about therapy
      for bipolar disorder mirror those that exist whenever new treatments, including
      medications, are introduced into routine clinical practice. Many of these key
      questions relate to differences between efficacy and effectiveness of adjunctive
      therapies, the long-term durability of any benefits and mechanisms by which
      therapies achieve their effects. These can be explored using currently existing
      scientific paradigms.

PMID- 18087203
TI  - Duloxetine does not relieve painful physical symptoms in depression: a meta
      analysis.
AB  - BACKGROUND: Duloxetine inhibits both serotonin and norepinephrine reuptake and is
      marketed as a treatment for both the core emotional symptoms and painful physical
      complaints that often accompany depression. Some studies have found that
      duloxetine is efficacious in treating painful symptoms associated with depression
      but these findings have been inconsistent. Several narrative review articles have
      reached positive conclusions about the efficacy of duloxetine as an analgesic in
      depression but there has been no quantitative systematic review regarding the
      impact of duloxetine on pain among this population. A meta-analysis of data
      pertaining to duloxetine's purported analgesic effects on depressed patients was
      thus undertaken. METHODS: Studies were selected through searching Medline and
      Cochrane Trial databases as well as examining Lilly's public clinical trial
      database. A random effects model was used. RESULTS: Across five trials, the
      results indicate a very small (d = 0.115) and statistically nonsignificant (p =
      0.057) analgesic effect for duloxetine. Additionally, some of the relevant data
      on duloxetine's effects have not been reported fully, making it likely that the
      obtained results reflect an overestimate of its true impact on painful physical
      symptoms in depression. DISCUSSION: The current analysis is based on a small
      number of studies; further trials may yield significant results favoring
      duloxetine. Based upon the currently available evidence, the marketing of
      duloxetine as an antidepressant with analgesic properties for people with
      depression does not appear to be adequately supported.

PMID- 18087204
TI  - Continuation and maintenance use of antidepressants in recurrent depression.
AB  - BACKGROUND: Maintenance antidepressant (AD) medication is the most commonly used
      preventive strategy in a highly recurrent disease, i.e. depression. Little is
      known about the discontinuation of maintenance AD use and the association with
      recurrence in daily clinical practice. The purpose was to examine the
      discontinuation rate of maintenance AD in daily clinical practice in recurrently
      depressed patients and the associated risk of recurrence. METHODS: Prospectively
      AD maintenance medication and recurrence were examined in 172 euthymic patients
      with recurrent depression. AD user profiles before recurrence (nonusers,
      intermittent users, continuous users) were examined and related to recurrence
      over a 2-year follow-up period. RESULTS: Less than half of the patients (42%)
      used AD continuously. Taking into account the minimal required adequate used
      dosage (> or = 20 mg fluoxetine equivalent), only 26% of the patients used AD as
      recommended by international guidelines. Despite continuous use of AD, 60.4%
      relapsed in 2 years. This relapse rate was comparable to the rate of the
      intermittent users (63.6%). In patients who stopped taking AD after remission and
      who received additional preventive CT, the recurrence rates were significantly
      lower than in non-AD-using patients treated with usual care (8 vs. 46%).
      CONCLUSIONS: The majority of recurrently depressed patients treated with AD
      discontinue maintenance AD therapy in daily primary and secondary clinical
      practice. AD seems to offer poor protection against relapse in this patient
      group. Patients who stopped using AD experienced less relapse, especially if they
      were treated with preventive CT. Alternative maintenance treatments (including
      preventive cognitive therapy after discontinuation of AD) should be studied in
      recurrently depressed patients with intermittent good remission, not only in
      secondary but also in primary care.

PMID- 18087205
TI  - Predictors of treatment response for depression and inadequate social support-
      the ENRICHD randomized clinical trial.
AB  - OBJECTIVE: To determine whether the 'dose' of treatment exposure, delivery of
      specific components of cognitive behavior therapy (CBT), patient adherence and/or
      use of antidepressants predict favorable depression and social support outcomes
      after 6 months of cognitive behavioral treatment. METHODS: Secondary analyses of
      the intervention arm of the Enhancing Recovery in Coronary Heart Disease
      (ENRICHD) clinical trial involving persons with acute myocardial infarction (MI):
      n = 641 for the depression outcomes and n = 523 for the social support outcomes.
      The outcome measures were, for depression: the Beck Depression Inventory (BDI)
      and Hamilton Rating Scale for Depression (HAM-D); for social support: the ENRICHD
      Social Support Instrument (ESSI) and Perceived Social Support Scale (PSSS).
      RESULTS: Better depression outcomes (measured by the BDI) were receiving a high
      number of depression-specific intervention components, p < 0.01, and completing a
      high proportion of homework assignments, p < 0.02. Better depression outcomes
      (measured by the HAM-D) were receiving a high number of the social communication
      and assertiveness components of the intervention, p < 0.01, and completing a high
      proportion of homework assignments, p < 0.01. Better social support outcomes
      (measured by the ESSI and PSSS) were predicted by membership in a racial or
      ethnic minority group, p < 0.02 and p < 0.01, respectively; and by completing a
      higher number of homework assignments, p < 0.01 and p < 0.05, respectively.
      Delivery of the social communication and assertiveness components of the
      intervention was an independent predictor of a worse social support outcome, p <
      0.01 (measured by the PSSS). CONCLUSIONS: The standard components of CBT for
      depression are useful in treating comorbid depression in post-MI patients.
      Working on communication skills may help to improve depression but not
      necessarily social support outcomes in this patient population, while adherence
      to cognitive-behavioral homework assignments is important for both outcomes.
      Other components of the ENRICHD intervention that were designed to improve social
      support had no discernible effects on outcomes. Intervention refinements may be
      needed in order to achieve better results in future post-MI clinical trials. A
      greater emphasis on CBT homework adherence could improve both depression and
      social support outcomes.

PMID- 18087206
TI  - Cognitive versus behavior therapy: processes of change in the treatment of
      obsessive-compulsive disorder.
AB  - BACKGROUND: Behavior therapy [exposure and response prevention (ERP)] and
      cognitive therapy (CT) have proven effective in the treatment of obsessive
      compulsive disorder. Direct comparisons between these treatment modalities have
      exposed no differences in efficacy. However, very little research has been
      conducted into the differences between the change processes in ERP and CT. This
      investigation is a first attempt to study change by measuring scores on a weekly
      basis rather than at specific stages in the treatment and follow-up. METHODS: We
      used the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at weekly intervals to
      rate and compare the severity of the obsessions and compulsions of 61 completers
      of either CT or ERP. The aim was to ascertain whether the process of change in CT
      is different from the process of change in ERP. We expected that ERP would
      primarily affect behavior, thus reducing compulsions first, while CT would
      primarily affect thought, thus reducing obsessions first. RESULTS: Firstly, no
      differences were found between ERP and CT with respect to the change process for
      obsessions and compulsions. Secondly, it emerged that changes in compulsions
      predicted all treatment effects better than changes in obsessions. CONCLUSIONS:
      These results suggest that reduction of compulsions is the process through which
      both ERP and CT affect change.

PMID- 18087207
TI  - Systemic family therapy in schizophrenia: a randomized clinical trial of
      effectiveness.
AB  - BACKGROUND: Although evidence suggests the effectiveness of cognitive and
      behaviorally oriented family therapies for schizophrenia, no specific randomized
      study has been carried out on Systemic Family Therapy (SFT). The purpose of this
      longitudinal prospective study was to evaluate the clinical effectiveness of SFT
      in the treatment of patients suffering from schizophrenia, as compared with a
      control case sample composed of patients undergoing routine psychiatric
      treatment. The study included a 2-year follow-up period and was conducted
      following the Milan School model. METHODS: The case sample in the study was made
      up of 20 patients treated with SFT associated with routine psychiatric treatment,
      and 20 patients undergoing routine psychiatric treatment alone. Both groups of
      patients were re-evaluated at the end of treatment (T1) and 12 months after the
      end of treatment (T2) to assess the clinical course of the illness. RESULTS: At
      the end of the follow-up period, we noticed an improved clinical course and a
      better pharmacological compliance in the group of patients treated with SFT. In
      the experimental case sample, 3 subjects (15%) had relapsed, compared to 13
      patients (65%) in the control group (p = 0.03). No significant difference was
      found in the 2nd year of follow-up. CONCLUSIONS: Our study provides an innovative
      contribution with regard to the evaluation of the clinical effectiveness of SFT
      in the treatment of schizophrenic patients. The clinical results were
      significant, and we thus feel justified in continuing to use this type of therapy
      in integrated interventions involving schizophrenic patients.

PMID- 18087208
TI  - Posttraumatic embitterment disorder in comparison to other mental disorders.
AB  - BACKGROUND: The term 'posttraumatic embitterment disorder' (PTED) was recently
      introduced to describe a subtype of adjustment disorders, characterized by
      prolonged embitterment, severe additional psychopathological symptoms and great
      impairment in most areas of life in reaction to a severe negative but not life
      threatening life event. The aim of this study is an empirical description and
      validation of the clinical concept of PTED, by comparing clinically defined PTED
      patients with patients suffering from other mental disorders on measures of
      posttraumatic stress and psychopathological distress. METHODS: Fifty inpatients,
      suffering from PTED according to previously defined clinical diagnostic criteria,
      were compared with another 50 patients, matched by age and gender, who did not
      meet clinical criteria for PTED but for other mental disorders. Psychiatric
      diagnoses were assessed by the Mini International Neuropsychiatric Interview.
      Self-report measures included the Bern Embitterment Scale, the Impact of Event
      Scale, the PTED Self-Rating Scale and the SCL-90. RESULTS: According to the Mini
      International Neuropsychiatric Interview both groups fulfilled the criteria for
      many disorders with a significantly higher occurrence of major depression and
      chronic adjustment disorder but less generalized anxiety disorder lifetime in
      PTED patients. Patients with PTED scored significantly higher on the global
      scores and on most subdimensions of the SCL-90, the Impact of Event Scale, the
      Bern Embitterment Scale and the PTED Self-Rating Scale. CONCLUSIONS: Clear
      differences were found between PTED patients and patients with other mental
      disorders in regard to the quality and intensity of psychopathological as well as
      posttraumatic stress symptoms. PTED can help further subclassify and specify
      adjustment and reactive disorders.

PMID- 18087209
TI  - Repetitive transcranial magnetic stimulation in bulimia nervosa: preliminary
      results of a single-centre, randomised, double-blind, sham-controlled trial in
      female outpatients.
AB  - BACKGROUND: Bulimia nervosa (BN) is often associated with depressive symptoms and
      treatment with antidepressants has shown positive effects. A shared deficient
      serotonergic transmission was postulated for both syndromes. The left
      dorsolateral prefrontal cortex was argued to regulate eating behaviour and to be
      dysfunctional in eating disorders. METHODS: Fourteen women meeting DSM-IV
      criteria for BN were included in a randomised placebo-controlled double-blind
      trial. In order to exclude patients highly responsive to placebo, all patients
      were first submitted to a one-week sham treatment. Randomisation was followed by
      3 weeks of active treatment or sham stimulation. As the main outcome criterion we
      defined the change in binges and purges. Secondary outcome variables were the
      decrease of the Hamilton Depression Rating Scale (HDRS), the Beck Depression
      Inventory (BDI) and the Yale-Brown Obsessive Compulsive Scale (YBOCS) over time.
      RESULTS: The average number of binges per day declined significantly between
      baseline and the end of treatment in the two groups. There was no significant
      difference between sham and active stimulation in terms of purge behaviour, BDI,
      HDRS and YBOCS over time. CONCLUSION: These preliminary results indicate that
      repetitive transcranial magnetic stimulation (rTMS) in the treatment of BN does
      not exert additional benefit over placebo. A larger number of patients might
      clarify a further role of rTMS in the treatment of BN.

PMID- 18087210
TI  - Alexithymia, negative feelings in the patient and pejorative feelings in the
      clinician.

PMID- 18087211
TI  - Alexithymia, depression and sleep disturbance symptoms.

PMID- 18087212
TI  - The influence of a non-occlusive bi-layer composite membrane on skin barrier
      properties. A non-invasive evaluation with a right-left intra-individual pre/post
      comparison study.
AB  - The purpose of this placebo-controlled right-left intra-individual pre/post
      comparison study was to evaluate the efficacy of a new bi-layer composite
      membrane, composed of a layer of knitted cotton and a layer of semi-permeable
      polyurethane, developed in order to improve skin hydration. Eighteen healthy
      subjects entered the study. A T-shirt, dedicated to this study, was prepared and
      it was worn for 8 h, mimicking overnight wearing. Before and at the removal of
      the T-shirt an objective quantification of skin parameters was performed by
      measuring hydration, transepidermal water loss (TEWL) and skin surface pH,
      bilaterally, on the inner side of the forearm. Measurements were performed both
      at the interface between the skin and the bi-layer composite membrane or cotton
      and on the outer side of the membrane (to assess permeation of water and
      occlusive properties of the product) with and without a single application of a
      moisturizer. A statistically significant improvement of skin hydration, recorded
      on the stratum corneum underneath the bi-layer membrane versus cotton alone, was
      measured both with (p < 0.0001) and without application of the moisturizer (p <
      0.002). TEWL was shown to decrease significantly on the side of the bi-layer
      membrane, if compared with cotton (p < 0.008), after application of the
      moisturizer. TEWL through the membrane showed no significant differences as
      compared to placebo, confirming the permeability of the fabric. Our data suggest
      that this bi-layer composite membrane can promote the hydration process of the
      stratum corneum, increasing the hydrating properties of the moisturizer agent.

PMID- 18087213
TI  - Differential lysis of tumors by polyclonal T cell lines and T cell clones
      specific for hTERT.
AB  - The human telomerase reverse transcriptase hTERT is overexpressed in most human
      tumors and contributes importantly to oncogenesis by maintaining the integrity of
      telomeric DNA. Despite being a self-antigen, the hTERT enzyme is immunogenic.
      Peptides derived from hTERT have been shown both in vitro and in vivo to drive
      the activation and proliferation of peptide-specific T lymphocytes. An HLA-A2
      binding peptide from Htert (I540, ILAKFLHWL) has been used to generate peptide
      specific T cells in vitro and in vivo in patients that lyse telomerase-positive
      tumors in an MHC-restricted fashion. Although these and other data suggest that
      I540 is naturally processed and presented on the surface of certain tumor cells,
      there are reports that I540-specific T cells, and in particular, T cell clones,
      do not lyse tumors in vitro. Here, we compared cytotoxic function of I540-specfic
      T cell clones vs. polyclonal T cell lines, including clones and lines generated
      from the same donor. We found that I540-specific polyclonal T cell lines lyse
      telomerase-positive tumors whereas non-specific polyclonal T cell lines and I540
      specific T cell clones do not. Estimated TCR avidity for I540, as well as cell
      surface expression of CD45RO, CD45RA, CD28, CD27, CD57 and CD62L were similar
      between lines and clones. V beta usage, however, differed such that the majority
      of the I540-specific TCR repertoire found in polyclonal T cell lines was not
      represented in clones generated from the same source material. Thus, I540
      specific T cells can vary in cytotoxic potential depending on the method of
      generation, isolation and expansion.

PMID- 18087214
TI  - Expression of dystroglycan correlates with tumor grade and predicts survival in
      renal cell carcinoma.
AB  - The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a
      continuous link from the extracellular matrix to the actin cytoskeleton.
      Deregulated expression of DG has been reported in a variety of human malignancies
      and related to tumor aggressiveness. In this study expression of the DG subunit
      was evaluated by immunostaining in a series of renal epithelial cancers and its
      relation with traditional prognostic indicators and with the clinical outcome of
      the patients was evaluated. alphaDG expression was undetectable in a significant
      fraction of tumors (54%). In renal cell carcinomas (RCC) loss of alpha-DG
      staining correlated with higher tumor grade (p = 0.02) but not with tumor stage
      nor tumor size. In clear cell RCC patients loss of alphaDG staining correlated
      with an increased risk of recurrence (p = 0.002 by log-rank test) and death (p =
      0.004) also when patients with lower grade or stage tumors were analyzed
      separately. In a multivariate analysis loss of DG staining confirmed to be and
      independent predictor of shorter disease-free (p = 0.001; RR = 4.9) and overall
      (p = 0.009; RR = 4.9) survival stronger than tumor grade and size. These findings
      demonstrate that loss of alphaDG expression, which correspond to loss of a
      functional DG complex, is a frequent event in human renal tumorigenesis and is an
      independent predictor of early recurrence and death for patients with clear cell
      RCC.

PMID- 18087217
TI  - Expression of immune-related molecules in primary EBV-positive Chinese
      nasopharyngeal carcinoma: associated with latent membrane protein 1 (LMP1)
      expression.
AB  - To understand the role of Epstein-Barr virus (EBV) and viral products in
      associated with immunophenotype and clinical outcome of primary nasopharyngeal
      carcinoma (NPC), the expression levels of chemokines IFN-g-induced protein 10 (IP
      10, CXCL10), stromal-derived factor-1 (SDF-1, CXCL12) and its receptor CXCR4 was
      investigated in 56 primary NPC biopsy specimens from Chinese NPC patients in
      parallels with LMP1 antigen and EBER1 by immunohistochemisty (IHC) and in situ
      hybridization (ISH). Moreover, the expression levels of HLA class I (b
      microglobulin) and II antigen (HLA-DR), and co-stimulatory molecule CD54 were
      also evaluated in 31 out of these 56 patients using immunohistochemisty (IHC).
      Our results showed that (a) the elevated expression levels of IP10, SDF-1, CXCR4,
      b-microglobulin, HLA-DR and CD54 in NPC lesions was 66%, 36%, 30%, 42%, 55% and
      69%, respectively. (b) High expression of SDF-1 was observed in advanced NPC (N
      stage, p < 0.05). (c) LMP1 expression correlated with upregulation of CXCR4 and
      translocation of CXCR4 to the nucleus of the tumor cells. This role of LMP1 in
      regulating the expression of CXCR4 was confirmed in the EBV positive NPC cell
      line C666 by inhibition of LMP1 expression with small interfering RNA (siRNA).
      Our findings provide new insights on the immune status of the malignant cells
      which may affect the outcome of immunotherapy in NPC. The differentiated
      nonkeratinizing and undifferentiated types of nasopharyngeal carcinoma (NPC) are
      associated with Epstein-Barr virus (EBV) in South China, which has the highest
      incidence rate in the world. The EBV latent type II antigens include nuclear
      antigen 1 (EBNA1), and latent membrane protein 1 (LMP1, in approximately 50%,
      seen in ref. 2) and protein 2 (LMP2), in addition small non-polyadenylated viral
      RNAs non-coding nuclear RNAs (EBERs) and BamHI-A rightward transcripts (BARTs)
      expressed in NPC tumor cells. The expressions of EBV antigens in NPC tumor cells
      provide the targets for adoptive immunotherapy. However, the poorly
      differentiated NPC is always characterized by the presence of a highly cellular
      lymphoid stroma admixed with tumor cells. However, the role of local immunity
      surrounding NPC cells and the role EBV and viral products expressed in tumor cell
      remain unclear, which is associated with the expression of immune-related
      molecules including chemokines and receptors, HLA class I and II antigens, and co
      stimulatory molecules and the role of EBV and viral products to alter the
      expression of immune-related molecules on tumor cells. It has been reported that
      the expression pattern of immune related-molecules on tumor cells will affect the
      outcome of T-cell-based adoptive immunotherapy for NPC.

PMID- 18087216
TI  - TRAF4 is potently induced by TAp63 isoforms and localised according to
      differentiation in SCCHN.
AB  - p63, a member of the p53 family, is overexpressed in squamous cell carcinoma of
      the head and neck (SCCHN) and some other tumors of epithelial origin. As a
      transcription factor, p63 can bind to p53-type response elements and there is
      some overlap between p53 family transcriptional targets. Tumor necrosis factor
      receptor associated factor 4 (TRAF4) is a p53 regulated gene which is
      overexpressed in many human carcinomas. We investigated the involvement of p63 in
      regulation of TRAF4 and the expression of the TRAF4 protein in SCCHN. Disrupting
      endogenous p63 expression resulted in downregulation of TRAF4 mRNA and protein in
      an SCCHN cell line. Endogenous p63 bound to the TRAF4 promoter in vivo and
      reporter assays showed that p63, p73 and p53 can all transactivate TRAF4, with
      TAp63 isoforms being the most potent activators. The level of TRAF4 activation by
      TAp63 was two-fold higher than by p53, and TRAF4 was ten-fold more responsive to
      TAp63 than another p63-target, IGFBP3. Nuclear expression of TRAF4 was seen in
      normal oral epithelium and highly/moderately differentiated SCCHN, whereas
      cytoplasmic expression of TRAF4 was seen in poorly differentiated SCCHN. These
      results indicate that TRAF4 is a common target of p53 family members and that
      localization of TRAF4 is associated with differentiation of SCCHN cells.

PMID- 18087215
TI  - Microarray analysis of p53-dependent gene expression in response to hypoxia and
      DNA damage.
AB  - Hypoxia is a common feature of solid tumors and promotes resistance to apoptosis
      from cancer therapies that induce DNA damage. The mechanism for this resistance,
      however, remains unclear. Since activation of the p53 pathway plays a major role
      in determining whether cells undergo apoptosis in response to DNA damage, we
      performed a microarray analysis of p53-dependent gene expression changes in
      response to DNA damage combined with hypoxia. When the H460 human lung cancer
      cell line was treated with hypoxia and etoposide, a chemotherapy agent that
      induces double-stranded DNA breaks, the dominant transcriptional response was
      regulated by DNA damage in a p53-dependent manner. Interestingly, however, DNA
      damage combined with hypoxia modulated both the intensity of the p53 response and
      the composition of downstream target genes. For example, there was synergistic
      activation of known p53 target genes such as p21 and gadd45, and the unique
      induction of other potentially novel p53 target genes including Rad and I-Rel. In
      addition, analysis of repressed genes supported a model for antagonism of c-Myc
      signaling in hypoxia, based on the downregulation of several known c-Myc target
      genes and the induction of Mxi1, a c-Myc antagonist. These data suggest a
      hypothesis that the combination of hypoxia and DNA damage promotes resistance to
      therapy by eliciting a transcriptional response that favors cell cycle arrest
      over apoptosis.

PMID- 18087218
TI  - New enlightenment of French Paradox: resveratrol's potential for cancer
      chemoprevention and anti-cancer therapy.
AB  - Resveratrol is a phytoalexin produced by many plants, and the skin of red grapes
      is particularly rich in resveratrol which accounts for the "French Paradox".
      Besides its protection of the cardiovascular system, it can affect the processes
      underlying all three stages of carcinogenesis, involving tumor initiation,
      promotion and progression. It has also been shown to suppress angiogenesis and
      metastasis. The anti-carcinogenic effects of resveratrol appear to be closely
      associated with its capacity to interact with multiple molecular targets involved
      in cancer development, while minimizing toxicity in normal tissues as tested. By
      reviewing many in vitro and in vivo studies, also considering both the supporting
      and challenging evidences, we are provided with a theory in support of the use of
      resveratrol in human cancer chemoprevention, in combination with either
      chemotherapeutic drugs or cytotoxic factors for the highly efficient treatment of
      drug refractory tumor cells. Anti-carcinogenic potential for cancer
      chemoprevention and anticancer therapy, which is one of the pleiotropic effects
      of resveratrol, is so called a new enlightenment of French Paradox.

PMID- 18087219
TI  - BRCA1 regulates gamma-tubulin binding to centrosomes.
AB  - Centrosomes are the cellular organelles that nucleate microtubules (MTs) via the
      activity of gamma-tubulin ring complex(s) (gammaTuRC) bound to the pericentriolar
      material of the centrosomes. BRCA1, the breast and ovarian cancer specific tumor
      suppressor, inhibits centrosomal MT nucleation via its ubiquitin ligase activity,
      and one of the known BRCA1 substrates is the key gammaTuRC component, gamma
      tubulin. We analyzed the mechanism by which BRCA1 regulates centrosome function
      using an in vitro reconstitution assay, which includes separately staged steps.
      Our results are most consistent with a model by which the BRCA1 ubiquitin ligase
      modifies both gamma-tubulin plus a second centrosomal protein that controls
      localization of gammaTuRC to the centrosome. We suggest that this second protein
      is an adapter protein or protein complex that docks gamma-TuRC to the centrosome.
      By controlling gamma-TuRC localization, BRCA1 appropriately inhibits centrosome
      function, and loss of BRCA1 would result in centrosome hyperactivity,
      supernumerary centrosomes and, possibly, aneuploidy.

PMID- 18087220
TI  - Contribution of dendritic cells' FcgammaRI and FcgammaRIII to cross-presentation
      of tumor cells opsonized with the anti-MHC class I monoclonal antibodies.
AB  - Dendritic cells (DC) operate through an immature (iDC) step (where tumor antigens
      are internalized) and a mature step (mDC) (where tumor antigens (TA) are cross
      presented to naive TA-specific cytotoxic T lymphocyte (CTL) progenitors).
      Receptors by which cellbound antigens can access the DC cross-presentation
      pathway include the Fcgamma receptors (FcgammaR). This route has been exploited
      to deliver opsonized tumors to DC and promising results have been obtained with
      mAbs raised against overexpressed or specific tumor antigens. In order to extend
      this strategy to tumor for which no antigens have been described, we have
      exploited the ubiquitous molecule MHC Class I as target antigen. The low membrane
      expression of tumor antigens on KATO cells, a previously studied human gastric
      carcinoma cell line, suggested its use here as a model. The IgG1 TP25.99 and the
      IgG2a W6/32 anti-MHC Class I mAbs, which strongly reacted with KATO cells, where
      employed as tumor coating mAbs. Since these mAbs recognize the FcgammaRI (CD64)
      and FcgammaRIII (CD16), respectively on DCs, the frequencies of the two classes
      of FcgammaRI on DCs was evaluated. CD64 was expressed on 35% of iDCs compared to
      11% expression of CD16, the two molecules being co-expressed. IgG1 mAb-opsonized
      KATO (KATO(TP25)) cells were taken up by iDCs with the same efficiency as KATO
      cells opsonized with IgG2a mAb (KATO(W6/32)), but induced a higher expression of
      the maturation marker CD83. CTL cross-priming by KATO(TP25) (but not KATO(W6/32))
      loaded and cytokine-matured DCs was also higher than cross-priming induced by
      uncoated- or FcgammaRI-targeted KATO(W6/32)-DC. Together the present results
      indicate that: (i) MHC Class I antigens are advantageous antigens for targeting
      tumor cells to the FcgammaR-mediated cross-presentation pathway and (ii)
      immunogenic signals seem to be prevalently conveyed by FcgammaRIII.

PMID- 18087221
TI  - Coix seed extract, a commonly used treatment for cancer in China, inhibits
      NFkappaB and protein kinase C signaling.
AB  - A pharmaceutical grade extract of Coix lachryma-jobi seeds is currently the most
      commonly used treatment for cancer in China. Although clinical data support the
      use of this preparation of a Traditional Chinese Medicine for cancer treatment,
      biological basis for the activity of this preparation has not been previously
      established. To address this issue, we first evaluated the anti-neoplastic
      activity of a Coix extract emulsion in xenografts of MDA-MB-231 breast cancer
      cells and found that the extract significantly inhibits growth of MDA-MB-231
      xenografts in athymic nude mice. Using oligonucleotide microarrays, we determined
      that Coix seed extract also significantly affects gene expression in these cells,
      including downregulation of genes (such as COX-2 and matrixmetalloproteinases)
      that are considered to be important in neoplasia. The specific gene expression
      changes noted after Coix seed extract treatment are characteristic of inhibition
      of NFkappaB-dependent transcription, leading us to evaluate how the treatment
      affects that pathway. An NFkappaB-dependent reporter assay demonstrated dose
      dependant inhibition of NFkappaB signaling by treatment of cultures with the
      extract, and immunofluorescent microscopy found that these effects are associated
      with reduced translocation of the Rel-A/p65 subunit of NFkappaB to the nucleus.
      Coix extract also inhibits activity of protein kinase C, a major mediator of
      signal transduction and activator of NFkappaB. Thus, this Traditional Chinese
      Medicine-based cancer treatment affects cellular pathways of recognized
      importance in neoplasia.

PMID- 18087222
TI  - ATM prevents unattended DNA double strand breaks on site and in generations to
      come.
AB  - Ataxia telangiectasia (A-T) is a disorder characterized by cerebellar
      degeneration, immunodeficiency, genomic instability and genetic predisposition to
      lymphoid malignancies with translocations involving antigen receptor loci. The
      Ataxia Telangiectasia Mutated gene encodes the ATM kinase, a central transducer
      of DNA damage signals. Until recently, the etiology of the lymphoid phenotype in
      A-T patients and the mechanisms by which ATM ensures normal repair of DNA double
      strand break (DSB) intermediates during antigen receptor diversification
      reactions remained poorly understood. Last year, Bredemeyer et al. (Nature 2006;
      442:466-70) demonstrated that ATM stabilizes chromosomal V(D)J recombination DSB
      intermediates, facilitates DNA end joining and prevents broken DNA ends from
      participating in chromosome deletions, inversions and translocations. A more
      recent study by Callen et al. (Cell 2007; 130:63-75) highlighted the importance
      of ATM-mediated checkpoints in blocking the long-term persistence and
      transmission of un-repaired DSBs in developing lymphocytes. Collectively, these
      results have provided complementary mechanistic insights into ATM functions in
      V(D)J recombination that can account for the lymphoid tumor-prone phenotype
      associated with A-T.

PMID- 18087223
TI  - Cell cycle arrest by glucocorticoids may protect normal tissue and solid tumors
      from cancer therapy.
AB  - Glucocorticoids have been widely used as cotreatment for patients with cancer due
      to potent pro-apoptotic properties in lymphoid cells, reduction of nausea and
      diminishing acute toxicity on normal tissue. There are now data from preclinical
      and, to some extent, clinical studies, demonstrating that these medicaments are
      highly suspicious to induce therapy resistance in the majority of malignant solid
      tumors-irrespective of tumor origin and the nature of specific anticancer drugs
      or irradiation used for treatment. Despite these huge amounts of data, the
      underlying mechanisms of cell type-specific signaling by these steroid hormones
      are just beginning to be described. This review summarizes our present
      understanding of a relationship between glucocorticoid-induced reversible cell
      cycle arrest and therapy resistance in solid tumors. We give a summary of our
      current knowledge of decreased proliferation rates in response to glucocorticoid
      pre and combination treatment which are suspicious to be involved not only in
      protection of normal tissues, but also in protection of solid tumors from
      cytotoxic effects of anticancer agents. The inhibition of cell cycle progression
      by pretreatment with GCs may be crucially involved in switching the balance of
      several interacting pathways to survival upon treatment with GCs.

PMID- 18087224
TI  - [Axonal involvement in dysimmune neuropathies].
AB  - Dysimmune neuropathies, in common with other neuropathies, comprise an axonal
      impairment that it is primary or secondary to a demyelinating process. We
      consider here axonal impairment in the course of certain dysimmune neuropathies,
      such as the Guillain Barre syndrome, chronic inflammatory demyelinating
      polyradiculoneuritis and multiple conduction block neuropathy. We mention the
      fact that it is not always easy to evidence the axonal impairment, its severity
      and its potential for regeneration. The mechanisms of the axonal lesions stem
      essentially from the special and tight bonds between the axon and the Schwann
      cell, which in the central central nervous system are mirrored by the bonds
      between axons and oligodendrocytes. Indeed, myelinating Schwann cells modify the
      properties of the axon in the normal peripheral nervous system, and abnormal
      Schwann cells induce pathological modifications. The periods of appearance of the
      axonal impairment are nevertheless quite variable depending on the type of the
      dysimmune neuropathy: acute or chronic. Some Guillain-Barre syndromes may be
      distinguished by a severe axonal impairment, now well documented and referred to
      as AMSAN and AMAN. Various mechanisms of axonal impairment are discussed. The
      bond between axon and myelin means that any pathological process in Schwann cells
      leads to axonal impairment, with inflammatory processes having a direct impact on
      the axon: mechanism of typical 'by-stander effect', repressive role of
      endoneurial edema, direct dysimmune attack on axonal epitopes on the
      corresponding axolemma, especially on the GM1 gangliosides, intra-axonal
      accumulation of sodium and calcium due to disruption the voltage-dependent
      sodium/potassium ion channels, slow retrograde progression to anterior horn
      neurons and possibly also to posterior spinal cords. The treatment of the axonal
      impairment is not straightforward; it is based, in a first instance, on the
      direct relation between the severity of the demyelinating lesions and the axonal
      impairment. For the acute forms of typical Guillain-Barre syndrome, the value of
      plasma exchanges and intravenous immunoglobulins has demonstrated in double
      blind, randomized trials. For the chronic demyelinating inflammatory
      polyradiculoneuritis, corticotherapy, along with plasma exchange and the
      immunoglobulins, have also been shown to be effective. Immunosuppressor treatment
      has benefits, but it is hard to prove objectively. It is generally recognized
      that it is only useful if applied for a period of weeks, although this is
      currently a matter of debate. Other therapeutic options have been discussed and
      proposed, although to date there is a lack of proven efficiency: such treatments
      include neuroprotective agents and drugs which block sodium/potassium ion
      channels. It is increasingly difficult to propose new treatments with validated
      efficiency, due to the small number of patients presenting dysimmune neuropathies
      of the type discussed here that are both typical and suitable for inclusion in
      medium to long term studies.

PMID- 18087225
TI  - [Immune tolerance and control of CNS autoimmunity: from animal models to MS
      patients].
AB  - INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease resulting
      in demyelination and axonal loss within the central nervous system (CNS). An
      autoimmune reaction directed against CNS antigens contributes to the disease
      process. Since the CNS has long been considered as an immune privileged site, how
      such an immune response can develop locally has remained enigmatic. Recent data,
      mostly based on the study of animal models for MS, have shown that the CNS is in
      fact more permissive to the development of immune responses than previously
      thought. This observation is counterbalanced by the fact that immune tolerance to
      neural antigens can be induced outside the CNS. This review focuses on the
      mechanisms preventing CNS autoimmunity, which act in three separate tissues.
      STATE OF THE ART: In the thymus, expression of CNS auto-antigens promotes partial
      protection, notably through elimination of autoreactive T cells. In the secondary
      lymphoid organs, the remaining autoreactive T cells are kept under control by the
      thymus-derived naturally occurring regulatory T cells of the CD4(+) Foxp3(+)
      phenotype. In the CNS, multiple mechanisms including the local activation of
      regulatory T cells further limit autoimmunity. CONCLUSIONS AND PERSPECTIVES: A
      better understanding of the induction of regulatory T cells, of their mechanisms
      of action, and of approaches to manipulate them in vivo may offer new therapeutic
      opportunities for MS patients.

PMID- 18087226
TI  - [Current cell therapy strategies for repairing the central nervous system].
AB  - One of the chief contemporary goals of neurologists and neuroscientists is to
      find a way to overcome the debilitating effects of brain diseases, especially
      neurodegenerative diseases. Since very few molecules have been found to be
      efficient in curing the patients and even halting the progression of the
      symptoms, cell therapy is now seen as an attractive alternative. Two therapeutic
      strategies are currently under investigation: i) the "substitution" strategy,
      based on grafts of cells capable of differentiating in the appropriate cells and
      restoring lost functions and ii) the "neuroprotective" or "conservative" strategy
      aiming to increase the resistance of spared cells to the toxicity of their
      environment and to reinforce the body's own mechanisms of healing. Twenty years
      ago, foetal neuroblasts were the first cells to be transplanted in the brains of
      patients with Parkinson's or Huntington disease. A phase II clinical trial is
      presently conducted in France for the latter disorder. However, the numerous
      ethical and technical issues raised by the use of embryonic and foetal cells have
      directed the focus of clinicians and researchers towards substitute cell types.
      In this review, we summarise the main findings of the most recent basic studies
      and clinical trials based on: i) the grafting of surrogate adult cells such as
      bone marrow mesenchymal stem cells and olfactory ensheathing cells; ii) the
      potential therapeutic applications of neuropoiesis - the persistent neurogenesis
      in the brain - as a source for tissue engraftment and as self-repair by a
      person's own indigenous population of pluripotent cells and iii) immune-based
      therapy (autologous activated macrophages and T cell vaccination) as well as
      administration of immunomodulatory molecules. Unexpectedly, it has been found
      that undifferentiated adult stem cells can display immune-like functions when
      they home in on an inflamed brain area while immune cells and immunosuppressors
      can improve functional and morphological recovery when administered within the
      appropriate time-window. On the one hand, outcomes from substitution therapy
      trials are encouraging. They pave the way for an enlarged use of various adult
      cell types for various neurological disorders. On the other hand, clinical
      benefits of the neuroprotective therapy, still under close scrutiny, look rather
      promising. It is likely that, in a close future, the two strategies will be
      combined in order to efficiently repair the pathological, the damaged or the
      senescent brain.

PMID- 18087227
TI  - [Epidemiological and clinical aspects of CIDP].
AB  - The aim of this study is to give a current overview of CIDP. Indeed, since it was
      first described in 1975, this entity appears to have evolved considerably. Based
      on an analysis of 146 patients diagnosed with CIDP at the Centre de Reference de
      Pathologie Neuromusculaire Paris Est between January 2005 and August 2006, our
      study seeks to answer the following questions: What is the frequency of this
      neuropathy? What are the diagnostic criteria? What is the clinical spectrum of
      CIDP? What is the frequency of the various clinical variants? How many CIDP
      variants are associated with another disease, and with which other diseases? What
      is the frequency of CIDP associated with a monoclonal gammopathy? What is the
      range of possible outcomes, and is CIDP a severe disease? Are current treatments
      for CIDP satisfactory?

PMID- 18087228
TI  - [Electrophysiological diagnosis of inflammatory neuropathies].
AB  - Electrodiagnostic study is very important in the diagnosis of inflammatory
      neuropathies with clinical, biological or histopathological criterias. It
      initially affirms the existence of a neuropathy and then to define if the
      pathological process is demyelinating, axonal or more rarely mixed. It also
      specifies if it concerns only sensory fibers, motor fibers or both. This
      exploration thus will make it possible to define different sub-groups with, for
      each one, a possible etiological guidelines. In the subgroup of demyelinating
      neuropathies, except congenital neuropathies, the inflammatory neuropathies
      represent the main etiology with chronic infammatory demyelinating polyneuropathy
      as a model. In the group of axonal neuropathies, inflammatory etiology is not
      prevailing. But, according to the subtype of neuropathy (sensory, motor or mixed)
      and the possible asymmetrical presentation, it could be however possible to
      extract different electrophysiological entities and to guide the clinician
      towards various sub-groups among which the inflammatory etiologies are sometimes
      largely dominating (mononeuritis multiplex and ganglionopathies for example).

PMID- 18087229
TI  - [Neuropathy, monoclonal gammopathy and autoantibodies: how to establish a link?].
AB  - Monoclonal gammopathies are frequently observed in subjects older than 50 years.
      Understanding the pathogenetic role of paraproteins in peripheral nervous system
      damage is a necessary step to establish a link between the monoclonal gammopathy
      and neuropathy. The clinical, electrophysiological, biological and
      histopathological features of these neuropathies related to paraproteins are
      important to ensure appropriate treatments.

PMID- 18087230
TI  - [CIDP: diagnostic strategy when electromyography is not contributive].
AB  - The diagnosis of Chronic idiopathic demyelinating polyneuropathy (CIDP) is based
      on clinical, biological and electrophysiological data. Besides the easily
      recognized classic forms, there are many clinical variants, sometimes with
      paucisymptomatic presentation leading to uncertain diagnosis. Numerous sets of
      diagnostic criteria have sought to define CIDP, specially electrophysiological
      criteria. These criteria are more sensible than specific. We report two cases of
      CIDP. Electrodiagnostic studies did not show evidence of multifocal
      demyelination. We describe the other examinations available to diagnose CIDP.

PMID- 18087231
TI  - [Immune-mediated neuropathies: indications and value of nerve biopsy].
AB  - Diagnostic value of nerve biopsy in the diagnosis of chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP) has been widely discussed and
      indication has markedly decreased since 20 years. Diagnosis of CIDP is usually
      based on clinical features (progressive or relapsing course, symmetrical motor
      and sensory neuropathy in arms and legs, hypo or areflexia usually involve all
      four limbs), raised CSF protein concentration and nerve conduction studies
      consistent with demyelination. Several electrophysiological criteria for CIDP
      have been proposed. We presented a case of sensory-motor neuropathy with
      examination compatible with CIDP. Cerebrospinal fluid protein content has been
      slightly elevated. Electrophysiological criteria have been lacking due to absence
      of recorded compound motor action potential or sensory nerve action potential in
      lower limbs and absence of demyelination features in upper limbs. Sural nerve
      biopsy has allowed to show significant demyelination on microscopic and teased
      nerve fibers analysis. A diagnosis of CIDP has been kept and immunomodulatory
      treatment has been discussed. Intravenous immune globulin treatment has been
      effective in this patient. Nerve biopsy stay useful for confirmation of CIDP in
      front of clinical features compatible with the diagnosis but without usual
      biological and electrophysiological criteria. The confirmation of diagnosis is
      significant and can lead to effective treatment.

PMID- 18087232
TI  - [Chronic inflammatory demyelinating polyneuropathy (CIDP) revealing an associated
      disease diagnostic and therapeutic pitfalls].
AB  - The objective of this case report is to illustrate the problem's diagnosis of a
      CIDP revealing a associated disease. The patient had initially a sensory CIDP
      wich respond to prednisone. After 2 years, he worsened with motor deficit, pain
      and atypical skin's lesions. The diagnosis of POEMS syndrome was made only in the
      fourth research of monoclonal gammopathy. A specific treatment was realised but
      too late and a important motor deficit with axonal loss unfortunately persisted.

PMID- 18087233
TI  - [Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy
      (CIDP)].
AB  - Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy
      (CIDP) remains a difficult medical decision. Only plasma exchanges, intravenous
      immunoglobulins (IVIg) and corticosteroids are proven effective treatments.
      Immunosuppressors are actually not first-line treatments in CIDP. Particular CIDP
      forms are associated with different response to treatments: pure motor CIDP
      should be treated by IVIg, and corticosteroids should only carefully be used in
      Lewis-Sumner syndrome. Otherwise, IVIg are first-line treatment in diabetic
      patients. Patients must be informed of side's effects and expected clinical
      effects. Early treatment was actually not proved to prevent axonal damages in
      CIDP patients, and waiting seems to be the best therapeutic option in poorly
      symptomatic patients. Recently, clinical guidelines were proposed to help
      clinician in this treatment choice, but there is no consensus about the best
      dose, duration or administration way to CIDP treatments. Further studies should
      be performed to clarify these points and to determine immunosuppressor agents
      place in treatment strategy.

PMID- 18087234
TI  - [Dysimmune peripheral neuropathies: evaluation of treatment].
AB  - Despite a supposed common mechanism with demyelination, dysimmune peripheral
      neuropathies compose a heterogeneous group in term of symptoms (sensory, motor,
      autonomic), localization of lesions (focal, multifocal or widely spreaded) as
      well as evolutions (acute, relapsing or chronic). The lacks of reliable
      biological or electrophysiological markers of evolution in dysimmune neuropathies
      require development of clinical scales for therapeutic trials and therapeutic
      decisions in daily practice. As elaboration of a universal scale is not a
      realistic goal, several specific measurement tools have been proposed for
      dysimmune neuropathies this past ten years. Highlighting the interest of
      functional scales as the ONLS, the European INCAT group made a remarkable effort
      to validate these scales in dysimmune neuropathies. However, there is a
      controversy concerning the relative interest of deficit scales versus functional
      scales. The deficit scales may be more sensitive to progression of the disease
      whereas the functional scales reflect the impact of neuropathy. The use of
      composite scales, mixing the evaluation of deficits, electrophysiological data
      and functional issues, is a promising solution, but the relative value of these
      parameters still remains to be defined.

PMID- 18087235
TI  - [Chronic inflammatory demyelinating polyneuropathy and sarcoidosis: fortuitous
      association?].
AB  - We report the case of a 36-year-old-man who first presented two relapses of
      chronic inflammatory demyelinating polyneuropathy (CIDP) before a diagnosis of
      sarcoidosis was made. He subsequently presented two combined relapses of CIDP and
      sarcoidosis. Each time, the outcome was favorable after treatment with
      intravenous immunglobulins and steroids. The possible relationship between CIDP
      and sarcoidosis is discussed.

PMID- 18087236
TI  - [Chronic inflammatory demyelinating polyneuropathies: problem of the long-term
      therapeutic management].
AB  - INTRODUCTION: No guideline is available for the long-term therapeutic management
      of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). STATE OF THE ART:
      Efficacy of corticosteroids, intravenous immunoglobulins and plasma exchanges has
      been shown in trials conducted on short periods. Only experts'recommendations are
      available for management of patients after initiation of these treatments. For
      corticosteroids, decrease must be very slow on one or two years. With intravenous
      immunoglobulins, dose per cure must be diminished and then delay between cures
      extended. Other immunomodulators or immunosuppressors have been tested in CIDP in
      case of failure of standard treatment and if treatment dependence appears
      (cyclophosphamide, cyclosporine, azathioprine, mycophenolate, beta-1a interferon,
      rituximab, tacrolimus, etc.), but no controlled trials are yet available.
      Treatment of CIDP in the long term is very complex because this entity brings
      together very different patients. Thereby, in clinical and electophysiological
      series of the literature, therapeutic prognostic may depend on the delay between
      first symptoms and treatment, course of the disease, demyelinating pattern on EMG
      and development of axonal lesions. PERSPECTIVES/CONCLUSIONS: Progress in the long
      term treatment of CIDP depend on best diagnosis of the disease, fundamental
      research on pathophysiology to propose appropriate chemical molecules, and
      pursuit of trials with standard treatments on longer period and with others
      rhythm and way of administration. More recent treatments have to been tested in
      controlled trials too, in monotherapy or bi-therapy. Global cost in a patient
      treated for CIDP must be evaluated for each treatment. Multicentric approach of
      these questions will be recommended because of rarity of CIDP.

PMID- 18087237
TI  - Novel truncating mutations of the CHM gene in Chinese patients with
      choroideremia.
AB  - PURPOSE: Choroideremia (CHM) is an X-linked retinal degenerative disorder caused
      by mutations in the CHM gene. The mutations result in malfunction of the Rab
      escort protein 1 (REP-1). In this study, mutational analysis of the CHM gene was
      performed on five Chinese families clinically diagnosed with CHM. METHODS:
      Denaturing high performance liquid chromatography was used for mutation screening
      for all 15 exons and flanking intron regions of the CHM gene. Mutations were
      confirmed and characterized with DNA sequencing. Second samples were later
      collected for extraction of mRNA and proteins from leukocytes. A non-radioactive
      protein truncation test (PTT) was developed and used to characterize the
      truncating nature of the mutations. Immunoblot analysis of proteins extracted
      from leukocytes was also performed. RESULTS: Five mutations were identified in
      these five families, each with one distinct mutation: three frameshift, one
      nonsense, and one splicing. Two of these were novel mutations: c.627dupA in exon
      5 and c.703-1G>C in intron 5. The truncating nature of the mutations was
      experimentally proved by PTT for four families with second samples collected. In
      particular, c.703-1G>C spliced exon 5 directly to exon 7 and deleted the entire
      exon 6 from the transcript. Direct immunoblot analysis failed to detect REP-1 in
      males affected by CHM, but demonstrated its presence in female carriers and
      homozygous normal females. CONCLUSIONS: This is the first study reporting
      mutations in the CHM gene in Chinese families. Mutational analysis was performed
      at the DNA, mRNA and protein levels. Five truncating mutations were found, and
      two of these were novel.

PMID- 18087238
TI  - Endotoxin upregulates CCR7 and its ligands in the lymphatic-free mouse iris.
AB  - PURPOSE: Using time lapse intravital microscopy and histology, we previously
      reported that we could not detect migration of antigen-presenting cells from the
      iris to the regional lymph node. Dendritic cells (DC) in other peripheral tissues
      migrate to lymph nodes in response to chemokines, CCL19 (ELC) and CCL21b (SLC),
      that activate the CCR7 receptor. We hypothesized that DCs in an inflamed iris
      might show a different chemokine receptor and ligand profile, thus explaining the
      DC's inability to migrate. METHODS: Eyes of 35 BALB/c mice were injected
      intravitreally with 2 mul of 250 ng E. coli lipopolysaccharide (LPS) or phosphate
      buffered saline (PBS). Five mice served as naive controls. After 3 and 6 h, the
      iris-ciliary bodies were dissected and pooled in groups of five. Total RNA was
      isolated, and reverse-transcriptase polymerase chain reaction (RT-PCR) for
      chemokine receptor and ligand mRNA was performed. In addition, one eye from each
      of the three animals was taken 6 h after LPS injection for immunohistology (IHC).
      RESULTS: The naive iris, the iris after PBS injection, and the iris after LPS
      injection contained CCR5 mRNA at approximately equal levels and did not have
      detectable CCR6 mRNA. No CCR7 mRNA expression was found in the naive iris, but it
      was weakly expressed in PBS-injected eyes and was approximately 3.4 fold
      upregulated after LPS injection. This was confirmed by IHC with no staining for
      CCR7 in the control iris but positive staining in the inflamed eyes. Transcripts
      for the CCR7 ligands, CCL19 and CCL21b, were found after LPS or PBS injection but
      not in naive iris-ciliary bodies. CONCLUSIONS: The clear upregulation of CCR7 and
      its ligands in the inflamed iris suggests that another mechanism prevents iris
      DCs from migrating. Other possibilities include the absence of co-factors,
      inhibitory substances, the lack of lymphatics inside the eye, or inadequate
      biologicAL activity of these chemotactic factors and ligands.

PMID- 18087239
TI  - Expression of genes encoding glutamate receptors and transporters in rod and cone
      bipolar cells of the primate retina determined by single-cell polymerase chain
      reaction.
AB  - PURPOSE: Light signals from rod and cone photoreceptors traverse distinct types
      of second-order, bipolar neurons that carry these signals from the outer to inner
      retina. Anatomic and physiologic studies suggest that the specialization of rod
      and cone bipolar cells involves the differential expression of proteins involved
      in glutamatergic signaling. In a previous study, we compared the expression of
      genes for the AMPA- (GluR1-4) and kainate-sensitive (GluR5-7, KA1-2) ionotropic
      glutamate receptors, the metabotropic glutamate receptors (mGluR1-8), and five
      non-vesicular glutamate transporters (EAAT1-5) in full-complement cDNA
      constructed from fresh and aldehyde-fixed macaque retina using a technique
      suitable for amplification of a variety of differentially expressed transcripts.
      Here we apply the same protocol to compare expression of these genes in cDNA
      constructed from single rod and cone bipolar cells previously-labeled for
      morphological identification in fixed slices of macaque retina. METHODS: We used
      immunocytochemical labeling and unique morphological features in lightly fixed
      slices of macaque retina to target the rod bipolar or the DB3 cone OFF bipolar
      cell. Under visual control, we used a micropipette to target and extract labeled
      cells, and we isolated mRNA from each through enzymatic digestion. Full-length
      cDNA was synthesized using 3'-end amplification (TPEA) PCR, in which the highly
      diverse 3' regions were amplified indiscriminately to ensure detection of both
      high and low abundance genes. We used gene-specific RT-PCR to probe the cDNA of
      each bipolar cell both for expression of known genes to confirm cell
      identification as well as expression of genes encoding glutamate receptors GluR1
      7, KA1-2, and mGluR1-8 and for transporters EAAT1-5. RESULTS: Of 27 rod bipolar
      cells confirmed to express the genes for the a subunit of protein kinase C,
      mGluR6, and its G protein Galpha(o), 26 expressed at least one AMPA GluR subunit
      gene, 16 expressed at least two, and nine expressed three or more. Nearly every
      cell expressed the GluR4 gene (23/27), followed by GluR2 (16/27) and GluR1
      (11/27). In addition to mGluR6, 20/27 cells also expressed the mGluR3 gene.
      Nearly every rod bipolar cell also expressed the genes for the EAAT2 (23/27) and
      EAAT4 (21/27) transporters. Of 26 DB3 cells confirmed by expression of calbindin
      D-28 and absence of GAD-65/67, each expressed the gene for the AMPA subunit
      GluR4, followed by GluR2 (22/26), and GluR1 (15/26), the only kainate subunit
      gene expressed was GluR6 (18/26). Nearly every DB3 cell also expressed the gene
      for the EAAT2 transporter (25/26), but no others. CONCLUSIONS: Rod bipolar cells
      in the Macaca monkey retina expressed not only the mGluR6 gene, a subunit
      necessary for transmission of light-ON signals, but also nearly always GluR4 in
      combination with the glutamate transporter EAAT4 (21/27 cells). The DB3 cell
      involved in processing light-OFF signals from cones expressed most highly the
      combination of GluR4 and the transporter EAAT2 (25/26). These results suggest
      that glutamatergic signaling in rod and cone circuits in the primate retina
      depends upon complex molecular interactions, involving not only multiple
      glutamate receptor subunits, but also glutamate transporters. Our data
      demonstrate a consistent primary pattern for each cell type with subtle
      variability involving other genes. Thus, like neuronal cell types in other brain
      regions, morphological and physiologic homogeneity among retinal bipolar cell
      types does not exclude variations in expression that could serve to adjust the
      stimulus-response profile of each cell.

PMID- 18087240
TI  - X-linked idiopathic infantile nystagmus associated with a missense mutation in
      FRMD7.
AB  - PURPOSE: Infantile nystagmus is a clinically and genetically heterogeneous eye
      movement disorder. Here we map and identify the genetic mutation underlying X
      linked idiopathic infantile nystagmus (XL-IIN) segregating in two Caucasian
      American families. METHODS: Eye movements were recorded using binocular infrared
      digital video-oculography. Genomic DNA was prepared from blood or buccal-cells,
      and linkage analysis was performed using short tandem repeat (STR) and single
      nucleotide polymorphism (SNP) markers. Pedigree and haplotype data were managed
      using Cyrillic, and LOD scores calculated using MLINK. Mutation profiling of PCR
      amplified exons was performed by dye-terminator cycle-sequencing and analyzed by
      automated capillary electrophoresis. RESULTS: Video-oculography of affected males
      recorded conjugate, horizontal, pendular nystagmus with increasing-velocity
      waveforms in primary gaze converting to jerk nystagmus in eccentric gaze. Linkage
      analysis detected significantly positive two-point LOD scores (Z) at markers
      DXS8078 (Z=4.82, recombination fraction [theta]=0) and DXS1047 (Z=3.87, theta=0).
      Haplotyping indicated that the IIN locus mapped to the physical interval DXS8057
      (11.59 Mb)-rs6528335 on Xq25-q26. Sequencing of positional-candidate genes
      detected a c.425T>G transversion in exon-6 of the gene for FERM domain containing
      7 (FRMD7) that cosegregated with affected and carrier status. In addition, the
      same change was found to cosegregate with IIN in a genetically unrelated family
      but was not detected in 192 control individuals. CONCLUSIONS: The c.425T>G change
      is predicted to result in the missense substitution of the phylogenetically
      conserved leucine at codon 142 for an arginine (p.L142R), and supports a
      causative role for FRMD7 mutations in the pathogenesis of XL-IIN.

PMID- 18087241
TI  - Lacrimal gland inflammatory cytokine gene expression in the botulinum toxin B
      induced murine dry eye model.
AB  - PURPOSE: To determine the effect of keratoconjunctivitis sicca, induced by
      botulinum toxin-B (BTX-B), on the inflammatory cytokine gene expression in the
      lacrimal gland (LG). And to determine the effect of various topical anti
      inflammatory agents on the resulting cytokine levels. METHODS: Forty-two mice
      (eight-week-old, female, CBA/J) were divided into six groups. Four groups were
      injected with BTX-B into both lacrimal glands, one group was injected with saline
      into both LG (Sal, n=7), and one group served as an uninjected control (Con,
      n=7). The four groups of BTX-B injected mice were then assigned to a treatment
      group: 1. no additional treatment (BTX), 2. artificial tear treatment (AT), 3.
      Cyclosporine A (CSA) treatment, and 4. fluorometholone (FM) treatment (n=7 in
      each group). Corneal fluorescein staining was evaluated one, two, and four weeks
      after injection. LGs were harvested after two weeks (groups Con, Sal, and BTX)
      and four weeks (groups AT, CSA, and FM) after injection. Gene microarray analysis
      for inflammatory cytokines and their receptors, real time reverse-transcriptase
      polymerase chain reaction (RT-PCR), and immunofluorescent staining with anti
      mouse CD3e monoclonal antibody were then performed on LG tissue. RESULTS: BTX-B
      injection into the LG effectively induced dry eye in mice two and four weeks
      following injection. Microarray data identified the proinflammatory cytokines
      interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, IL-12, and macrophage
      migration inhibitory factor (MIF) and the anti-inflammatory cytokines IL-10 and
      toll-interacting protein (Tollip) as candidates for validation by real time RT
      PCR. MIF and IL-12 expression were elevated in BTX-B injected mice at weeks 2 and
      4 regardless of treatment. Tollip and IL-1 expressions were increased in some
      groups after BTX-B injection regardless of the treatment type. Other cytokines
      showed no significant changes. LG structures were well maintained without
      significant T lymphocyte infiltration in all groups. CONCLUSIONS: Ocular surface
      change induced by BTX-B injection resulted in an altered expression of various
      inflammatory cytokines in our murine dry eye model. Alteration of the pathology
      induced cytokine profile by topical therapy is reported.

PMID- 18087242
TI  - A comparative gene expression profile of the whole eye from human, mouse, and
      guinea pig.
AB  - PURPOSE: To characterize and compare gene expression patterns of the whole
      eyeball among human, mouse, and guinea pig based on expressed sequence tags
      (ESTs). METHODS: Approximately 10,000 clones were sequenced from the 5'-end for
      each cDNA library made from mRNAs isolated from whole eyeballs of human, mouse,
      and guinea pig. ESTs were assembled and analyzed based on standard methods.
      RESULTS: We acquired 31,464 high-quality ESTs including 9,949 for the human,
      11,495 for the mouse, and 10,020 for the guinea pig cDNA libraries, which were
      clustered into 12,253 unigenes for all three species. After removal of non-mRNA
      contaminations, we were able to match 96%, 97%, and 63% of the human, mouse, and
      guinea pig unigenes to sequences in the nonredundant library in GenBank,
      respectively. The high-abundance and medium-abundance genes in each library
      correlate with the anatomic structure and physiologic function of the eye in the
      three species. The large contribution from the lens in the mouse was related to
      the abundance of crystallin. Differentially expressed genes were observed among
      three libraries. Some of them appeared species-specific. CONCLUSIONS: According
      to their gene expression patterns, guinea pig and human eyes are more similar
      compared to those of the mouse, making the guinea pig a promising animal model
      for eye research.

PMID- 18087243
TI  - Is ectopia lentis in some cases a mild phenotypic expression of Marfan syndrome?
      Need for a long-term follow-up.
AB  - PURPOSE: Ectopia lentis (EL) and Marfan syndrome (MFS) are considered two
      distinct clinical entities. We performed genetic and clinical studies to
      investigate whether EL is actually distinct from MFS or if it is a mild
      phenotypic expression of it. METHODS: Seven patients with EL were followed for 5
      10 years. Mutation screening analysis of the 65 exons of FBN1 was performed by
      polymerase chain reaction (PCR) amplification of genomic DNA, denaturing high
      pressure liquid chromatography analysis, and direct sequencing of heteroduplexes.
      RESULTS: Yearly examinations during the 10 years of follow-up allowed the
      detection of a late onset of dural ectasia in six out of seven patients (age
      range: 32-64 years versus 8-55 years in MFS previously reported). We also
      detected the onset of mild thoracic aortic dilatation in a sporadic case (age
      45). Six out of seven index cases of EL turned out to be mild forms of Marfan
      syndrome with possible late cardiovascular involvement as detected in one case.
      Four novel missense mutations and one known splicing mutation were detected in
      five out of seven (71%) patients. Their localization confirmed the presence of a
      first hot spot within exons 1-15 and suggested the presence of a second one
      between exons 31-39. CONCLUSIONS: The presence of a second major criterion in six
      EL patients shifted the clinical diagnosis from EL to MFS. These data demonstrate
      that some cases, which are initially diagnosed as EL, turn out to be mild Marfan
      patients. A clinical cardiovascular follow-up is therefore highly recommended for
      all EL patients since they may develop thoracic aortic aneurysm (TAA) or
      dissection later in life. Also magnetic resonance imaging (MRI) for dural ectasia
      (DE) should be performed in a complete follow up for a MFS diagnosis.

PMID- 18087244
TI  - The role of Hsp70 and Hsp90 in TGF-beta-induced epithelial-to-mesenchymal
      transition in rat lens epithelial explants.
AB  - PURPOSE: This study investigates the effects of heat shock treatment and the role
      of Hsp70 and Hsp90 on tranforming growth factor beta 2 (TGF-beta2)-induced
      epithelial-to-mesenchymal transition (EMT) in rat lens epithelial explants.
      METHODS: Rat lens epithelial explants from 7 to 10 day-old Wistar rats were
      dissected and incubated for 24 h before treatment. The explants were divided into
      eight treatment groups: control (culture medium), fibroblast growth factor-2 (FGF
      2), TGF-beta2, and TGF-beta2+FGF-2 under normal culture conditions and heat
      shocked conditions. The explants were heat shocked at 45 degrees C before
      treatment with the respective media. H&E staining was performed on whole-mount
      epithelial explants from each group. Immunofluorescence staining for alpha-smooth
      muscle actin (alpha-SMA), F-actin, and E-cadherin was also used to determine EMT
      and fibrotic plaque formation in the lens epithelial explants. Apoptotic cell
      death was determined using the TUNEL (terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling) assay. Confocal microscopy was used to visualize
      immunoreactivity in the whole-mount epithelial explants. Western blot analysis of
      alpha-SMA, E-cadherin, Hsp70, and Hsp90 were also performed. RESULTS: TGF-beta2
      induced EMT and plaque formation in the lens epithelial explants. The
      simultaneous treatment of epithelial explants with TGF-beta2+FGF-2-induced the
      most significant morphological changes and EMT. Heat shock treatment of lens
      epithelial explants before TGF-beta2 treatment did not inhibit plaque formation,
      but there was significant reduction of alpha-SMA expression and greater E
      cadherin expression when compared to the non-heat shocked TGF-beta2-treated
      explants. Interestingly, TGF-beta-induced apoptotic cell death was significantly
      lower in the heat shocked explants compared to the non-heat shock lens explants.
      Heat-induced accumulation of Hsp70 and Hsp90 expression was reduced in the heat
      shocked groups at day 4 of treatment. CONCLUSIONS: TGF-beta2-induced EMT was
      significantly reduced in the heat shocked TGF-beta2 lens epithelial explants.
      After four days of culture, there is a reduction in expression of Hsp70 and Hsp90
      in the heat-shocked groups, indicating that the lens epithelial cells are under a
      less stressful condition than the non-heat shocked groups. In conclusion,
      molecular chaperones can play a protective role against TGF-beta2-induced EMT and
      enhance cell survival.

PMID- 18087245
TI  - Stepping up to the plate.

PMID- 18087246
TI  - Mentoring and networking: how to make it work.

PMID- 18087247
TI  - Akirins versus infection.

PMID- 18087248
TI  - IRF1: a deus ex machina in TH1 differentiation.

PMID- 18087249
TI  - Antigens take the shuttle.

PMID- 18087250
TI  - Bring out your dead.

PMID- 18087252
TI  - Semaphorins and their receptors in immune cell interactions.
AB  - Semaphorins are newcomers to the growing panoply of immunoregulatory proteins.
      Members of this family were originally identified as proteins that provide axonal
      guidance cues during neuronal development. However, accumulating evidence
      indicates that several semaphorins, called 'immune semaphorins', are crucial to
      various phases of the immune response, from initiation to terminal inflammatory
      processes. Extensive studies of immune semaphorins have shown not only
      differences but also parallels in semaphorin functions among physiologically
      distinct systems, providing unexpected but meaningful insights into the
      biological activities of this protein family. Here we review the present
      knowledge of the function of semaphorins and their receptors in the immune
      system, including the most recent advances in this field.

PMID- 18087260
TI  - Steady progress and recent breakthroughs in the accuracy of automated genome
      annotation.
AB  - The sequencing of large, complex genomes has become routine, but understanding
      how sequences relate to biological function is less straightforward. Although
      much attention is focused on how to annotate genomic features such as
      developmental enhancers and non-coding RNAs, there is still no higher eukaryote
      for which we know the correct exon-intron structure of at least one ORF for each
      gene. Despite this uncomfortable truth, genome annotation has made remarkable
      progress since the first drafts of the human genome were analysed. By combining
      several computational and experimental methods, we are now closer to producing
      complete and accurate gene catalogues than ever before.

PMID- 18087261
TI  - Single-polarity recombinant adeno-associated virus 2 vector-mediated transgene
      expression in vitro and in vivo: mechanism of transduction.
AB  - Recombinant adeno-associated virus 2 (AAV) vectors encapsidate single-stranded
      genomes of either polarity equally frequently in separate mature virions. Because
      viral genomes of either polarity are transcriptionally inactive, both the failure
      to undergo viral second-strand DNA synthesis and the failure to undergo DNA
      strand annealing have been proposed as possible reasons to account for the
      observed low efficiency of transgene expression. We compared the transduction
      efficiencies of conventional AAV vectors containing both [-] and [+] polarity
      genomes with those containing either the [-] or the [+] polarity genomes, in
      vitro as well as in vivo. We document that the transduction efficiency of single
      polarity AAV vectors is significantly enhanced by (i) co-infection with
      adenovirus; (ii) small interfering RNA (siRNA)-mediated down-modulation of a
      cellular protein, FKBP52, tyrosine-phosphorylated forms of which inhibit AAV
      second-strand DNA synthesis; (iii) over-expression of a cellular protein tyrosine
      phosphatase, T cell protein tyrosine phosphatase (TC-PTP), which catalyzes
      tyrosine-dephosphorylation of FKBP52; and (iv) deliberate over-expression of TC
      PTP, or the absence of FKBP52, respectively, in TC-PTP-transgenic mice and in
      FKBP52-knockout mice. These data confirm that viral second-strand DNA synthesis,
      rather than DNA strand annealing, is the rate-limiting step in efficient
      transduction by AAV vectors. This finding has implications in the use of these
      vectors in human gene therapy.

PMID- 18087262
TI  - DR5 activation of caspase-8 induces DC maturation and immune enhancement in vivo.
AB  - Non-homeostatic tissue apoptosis in vivo has been shown to induce inflammatory
      responses and facilitate the cross-presentation of proteins within apoptotic
      bodies. We hypothesize that in the presence of foreign antigens, the apoptotic
      inflammatory process improves immune priming; further, molecules that trigger
      apoptosis may be adapted for use as immune adjuvants. One very attractive
      molecule in this context is the tumor necrosis factor receptor (TNFR) family
      molecule DR5/TRAIL-receptor 2. We show a significant improvement in CD8(+) T-cell
      mediated vaccine immunity with the use of death receptor-5 (DR5) as an immune
      adjuvant, a property that is correlated with the activation of caspases-8 (casp8)
      and dependent on its ability to induce apoptosis in vivo.

PMID- 18087263
TI  - Time course and dynamics of adipose tissue development in obese and lean Zucker
      rat pups.
AB  - OBJECTIVE: To evaluate the ontogeny of adipose tissue dynamics in obese and lean
      Zucker rat pups, from suckling to puberty. METHODS: The trial had a two-group
      parallel design. Sixty-two male Zucker rat pups shared within 15 litters received
      deuterated water for 5 days, prior killing at different age. Adipose tissues were
      collected for (2)H-enrichment analyses using mass spectrometry to determine fat
      cell proliferation and lipid synthesis rates. Rats were assigned to obese and
      lean rat groups by genotyping. RESULTS: The time course (from days 13 to 55) of
      all adipose tissue growth showed that the highest fractional rates of fat cell
      proliferation, triacylglycerol (TG) synthesis and de novo lipogenesis (DNL) took
      place during early suckling in all rat pups. The appearance of excessive fat mass
      growth in the obese rats, as compared with lean rats, was first shown through a
      significant increase in DNL at the end of suckling (P<0.05). The TG synthesis
      rate was enhanced (P<0.05) from the end of suckling and early postweaning until
      day 55 (from 122+/-10 to 498+/-78 in obese pups and from 25+/-6 to 75+/-26 mg new
      TG per day in lean pups (median+/-s.e.m., P<0.01)). In contrast, only by day 55
      did the fractional proliferation rate of fat cells in retroperitoneal and
      epididymal depots in the obese rats supersede that of the lean rats (P<0.05).
      CONCLUSION: The early suckling period constitutes the most active period for
      adipose tissue development in normal rats. In the obese Zucker rat model, adipose
      hypertrophy primarily contributes to the early onset of obesity, while
      hyperplasia increases after puberty. Early onset of adipose tissue growth may
      play a determinant role in the development of obesity later in life.

PMID- 18087264
TI  - Shift in the composition of obesity in young adult men in Sweden over a third of
      a century.
AB  - OBJECTIVE: To assess whether the composition of the obese category (body mass
      index (BMI)> or =30) has changed during the last one-third of a century in young
      adult men. DESIGN: Retrospective study of 1,580,913 men (18.3+/-0.4 years)
      representing 82% of the Swedish male population at military conscription age
      between 1969 and 2005. Measured height and weight were used to define moderate
      and morbid obesity as BMI 30-34.9 and > or =35, respectively. Data on socio
      economic position (SEP), place of residence (urban, semi-urban and rural), age
      and test center were also collected. RESULTS: From the period 1969-1974 to 2000
      2005, the prevalence of moderate obesity almost quintupled (0.8-3.8%; P<0.0001),
      while morbid obesity increased 10-fold (0.1-1.3%; P<0.0001). The composition of
      the obese category changed from 12.9 to 25.1% morbidly obese during the same
      time, corresponding to an annual growth in the odds of 2.8% (CI(95%) 2.5-3.1%)
      per year within the obese category. Compared to 1969-1974, the odds ratios of
      obesity and morbid obesity, respectively, were 1.6 (1.6-1.7) and 1.9 (1.7-2.2) in
      1980-1984, 2.8 (2.7-2.9) and 4.0 (3.5-4.5) in 1990-1994, and 6.0 (5.7-6.3) and
      11.4 (10.1-12.9) in 2000-2005, after adjustment for SEP, urban/rural place of
      residence, age and test center. Extrapolation of the growth rate during the
      observation period resulted in an estimated 4% morbidly obese in 2020.
      CONCLUSION: Morbid obesity increased faster than moderate obesity during the last
      35 years. As the health risks and costs of obesity-related morbidity increase
      disproportionately in the morbidly obese, it is important to assess morbid
      obesity in prevalence studies, and distinguish the morbidly from the moderately
      obese in cost analyses.

PMID- 18087265
TI  - Allometric relationship between changes of visceral fat and total fat mass.
AB  - OBJECTIVE: To elucidate the mathematical relationship between changes of visceral
      adipose tissue (VAT) and total body fat mass (FM) during weight loss. DESIGN: We
      hypothesized that changes of VAT mass are allometrically related to changes of
      FM, regardless of the type of weight-loss intervention, as defined by the
      differential equation dVAT/dFM=k x VAT/FM, where k is a dimensionless constant.
      We performed a systematic search of the published literature for studies that
      included measurements of VAT changes via magnetic resonance imaging (MRI) or
      computed tomography (CT) imaging along with measurements of FM changes by dual
      energy X-ray absorptiometry, hydrodensitometry, air-displacement plethysmography
      or whole-body MRI or CT imaging. We then examined whether or not the data could
      be explained by the allometric model. RESULT: We found 37 published studies
      satisfying our search criteria, representing 1407 men and women of various
      ethnicities, degrees of adiposity and weight-loss interventions. The hypothesized
      allometric equation relating changes of VAT and FM accurately modeled the data
      for both men and women and for all methods of weight loss studied. The best-fit
      value for the dimensionless constant was k=1.3+/-0.1 and the resulting model had
      an R(2)=0.73. CONCLUSION: This is the first report to reveal an allometric
      relationship between changes of VAT and FM that holds for both genders as well as
      a wide variety of weight-loss interventions including bariatric surgery, caloric
      restriction with or without exercise and exercise alone. We conclude that changes
      of VAT are primarily determined by FM changes as well as the initial VAT to FM
      ratio.

PMID- 18087266
TI  - The thrifty gene hypothesis: maybe everyone is right?

PMID- 18087267
TI  - Metabolic syndrome and liver histology in paediatric non-alcoholic
      steatohepatitis.
AB  - OBJECTIVE: Our aim was to estimate prevalence of metabolic syndrome (MS), obesity
      and comorbidities in a cohort of 120 children (3-18 years) with biopsy-proven non
      alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) and
      to evaluate correlations between clinical or biochemical variables and liver
      histology. RESEARCH METHODS AND PROCEDURES: MS was diagnosed according to the
      adapted National Cholesterol Education Program criteria. Homeostatic model
      assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity
      check index (QUICKI); and ISI composite, insulin secretion (insulin response at
      30 min after a glucose load; HOMA-beta cell; insulinogenic index) were all
      estimated. BMI z-score and total body fat (dual-energy X-ray absorptiometry) were
      evaluated as indexes of obesity. RESULTS: MS was diagnosed in 66% of children.
      About 92% had weight above the 85th percentile, of which 42% were obese with
      weight above 97th percentile. Prevalence of hypertriglyceridaemia was 63%, low
      HDL cholesterol 45%, hypertension 40% and impaired glucose tolerance 10%. Levels
      of aminotransferases were higher as the number of comorbidities increased, the
      highest values being found in subjects with MS (P< or =0.05). Prevalence of a
      grade of steatosis > or =2 (P=0.05) and fibrosis (P< or =0.01) was higher in
      subjects with MS. Histology was associated significantly with higher values of a
      number of clinical and biochemical parameters (steatosis > or =2 with BMI z-score
      (P=0.04), fasting insulin (P=0.02), HOMA-IR (P=0.03), beta-cell secretion
      (P=0.04); necroinflammation with BMI z-score (P=0.007), glucose (P< or =0.0001),
      cholesterol (P< or =0.04) and white blood cells (P=0.025); fibrosis with body
      weight (P=0.05), BMI z-score (P=0.03), cholesterol (P=0.05), triglycerides
      (P=0.05), fasting insulin (P< or =0.0001) and mean values of the hormone at the
      OGTT (P=0.03), HOMA-IR (P< or =0.0001)). CONCLUSION: Presence of MS or clinical
      and biochemical variables associated with the syndrome seems to be strictly
      related to histological features of NASH in paediatric fatty liver disease. Thus,
      routinely liver biopsy should be encouraged in these children.

PMID- 18087270
TI  - Birth weight and melanoma risk: a population-based case-control study.
AB  - We investigated whether lower birth weight was associated with lower risk of
      melanoma later in life. This population-based case-control study included all
      incident cases of histologically verified invasive melanoma diagnosed until 31
      December 2003 in the Norwegian population born between 1967 and 1986 (n=709). The
      control group without malignant disease was established by random sampling from
      the same source population as the cases (n=108 209). Data on birth weight,
      gender, mother's residence and parental age at the time of birth were collected
      from the Medical Birth Registry of Norway and data on cancer from the Cancer
      Registry of Norway. The Mantel-Haenszel test of linear trend showed no trend in
      risk across the birth weight categories: individuals in the highest quartile of
      birth weight (>or=3860 g) had an odds ratio (OR) of 1.19 (95% confidence
      interval, CI: 0.77-1.84) compared to individuals with birth weight <2500 g. The
      adjusted OR was 0.81 (95% CI: 0.52-1.26) for birth weight below 2500 g (exposed).
      Though not statistically significant, the results suggest that low birth weight
      might influence the risk of melanoma later in life.

PMID- 18087271
TI  - The LLP risk model: an individual risk prediction model for lung cancer.
AB  - Using a model-based approach, we estimated the probability that an individual,
      with a specified combination of risk factors, would develop lung cancer within a
      5-year period. Data from 579 lung cancer cases and 1157 age- and sex-matched
      population-based controls were available for this analysis. Significant risk
      factors were fitted into multivariate conditional logistic regression models. The
      final multivariate model was combined with age-standardised lung cancer incidence
      data to calculate absolute risk estimates. Combinations of lifestyle risk factors
      were modelled to create risk profiles. For example, a 77-year-old male non
      smoker, with a family history of lung cancer (early onset) and occupational
      exposure to asbestos has an absolute risk of 3.17% (95% CI, 1.67-5.95). Choosing
      a 2.5% cutoff to trigger increased surveillance, gave a sensitivity of 0.62 and
      specificity of 0.70, while a 6.0% cutoff gave a sensitivity of 0.34 and
      specificity of 0.90. A 10-fold cross validation produced an AUC statistic of
      0.70, indicating good discrimination.If independent validation studies confirm
      these results, the LLP risk models' application as the first stage in an early
      detection strategy is a logical evolution in patient care.

PMID- 18087272
TI  - Prognostic role of serum cytokeratin 19 fragments in advanced non-small-cell lung
      cancer: association of marker changes after two chemotherapy cycles with
      different measures of clinical response and survival.
AB  - Prognostic implication of serum cytokeratin 19 fragments (CYFRA 21-1) was
      explored in 60 advanced NSCLC patients, whereas in 45 patients assessable for
      serological response a >or=35% CYFRA 21-1 decline after two chemotherapy cycles
      was strongly associated with non-progression (NP), defined as a sum of objective
      response (OR)+stable disease (P<0.0001) and survival (P=0.0002). Association of
      OR with survival was not significant. In multivariate survival analysis, >or=35%
      marker decline and radiological NP status were found as major determinants of
      prolonged survival with RR: 0.37 (P=0.01) and 0.63 (P=0.01), respectively. In
      advanced NSCLC patients, NP reflects therapeutic efficacy better than traditional
      OR. CYFRA 21-1 >or=35% decline seems to be a reliable surrogate marker of
      treatment efficacy in terms of survival.

PMID- 18087273
TI  - Long-term survival and transmission of INI1-mutation via nonpenetrant males in a
      family with rhabdoid tumour predisposition syndrome.
AB  - Rhabdoid tumour predisposition syndrome (RTPS) is a rare syndrome caused by
      inheritance of a mutated INI1 gene for which only two multigeneration families
      have been reported. To further characterise the genotype and phenotype of RTPS,
      we present a third family in which at least three cousins developed an atypical
      teratoid/rhabdoid tumour (AT/RT) at a young age. Two of these patients showed
      unusual long survival, and one of these developed an intracranial meningioma and
      a myoepithelioma of the lip in adulthood. Mutation analysis of INI1 revealed a
      germline G>A mutation in the donor splice site of exon 4 (c.500+1G>A) in the
      patients and in their unaffected fathers. This mutation prevents normal splicing
      and concomitantly generates a stop codon, resulting in nonsense-mediated mRNA
      decay. Biallelic inactivation of INI1 in the tumours, except for the meningioma,
      was confirmed by absence of nuclear INI1-protein staining. The myoepithelioma of
      one of the patients carried an identical somatic rearrangement in the NF2 gene as
      the AT/RT, indicating that both tumours originated from a common precursor cell.
      In conclusion, this study demonstrates for the first time transmission of a
      germline INI1-mutation in a RTPS family via nonpenetrant males, long-term
      survival of two members of this family with an AT/RT, and involvement of INI1 in
      the pathogenesis of myoepithelioma.

PMID- 18087275
TI  - Missing ligand model in autologous stem cell transplantation.

PMID- 18087276
TI  - Use of NSAIDs, smoking and lung cancer risk.
AB  - We investigated the risk of lung cancer in relation to non-steroidal anti
      inflammatory drugs (NSAIDs) among 573 cases and 857 sex- and age-matched controls
      for whom we had information on use of NSAIDs, from a prescription database
      covering all pharmacies in Denmark since 1995, and self-reported NSAID use,
      smoking habits and other potential confounders. Associations were expressed as
      odds ratios, assessed by logistic regression in unmatched analyses. After
      controlling for smoking habits, length of education and concomitant use of
      acetaminophen, we found a slightly decreased relative risk of 0.86 (95%
      confidence intervals, 0.65-1.14) for lung cancer associated with any use of
      NSAIDs. The risk decreased significantly (P=0.02) with increasing numbers of
      dispensed prescriptions per year during the 1-3 years before the index date with
      a relative risk of 0.49 (0.28-0.84) among those with four or more prescriptions
      per year during this period. Our findings suggest that regular use of NSAIDs is
      associated with a slightly or moderately reduced risk for lung cancer.

PMID- 18087277
TI  - Increased expression of phosphorylated forms of RNA-dependent protein kinase and
      eukaryotic initiation factor 2alpha may signal skeletal muscle atrophy in weight
      losing cancer patients.
AB  - Previous studies suggest that the activation (autophosphorylation) of dsRNA
      dependent protein kinase (PKR) can stimulate protein degradation, and depress
      protein synthesis in skeletal muscle through phosphorylation of the translation
      initiation factor 2 (eIF2) on the alpha-subunit. To understand whether these
      mediators are important in muscle wasting in cancer patients, levels of the
      phospho forms of PKR and eIF2alpha have been determined in rectus abdominus
      muscle of weight losing patients with oesophago-gastric cancer, in comparison
      with healthy controls. Levels of both phospho PKR and phospho eIF2alpha were
      significantly enhanced in muscle of cancer patients with weight loss irrespective
      of the amount and there was a linear relationship between phosphorylation of PKR
      and phosphorylation of eIF2alpha (correlation coefficient 0.76, P=0.005). This
      suggests that phosphorylation of PKR led to phosphorylation of eIF2alpha. Myosin
      levels decreased as the weight loss increased, and there was a linear
      relationship between myosin expression and the extent of phosphorylation of
      eIF2alpha (correlation coefficient 0.77, P=0.004). These results suggest that
      phosphorylation of PKR may be an important initiator of muscle wasting in cancer
      patients.

PMID- 18087278
TI  - Localisation pattern of Foxp3+ regulatory T cells is associated with clinical
      behaviour in gastric cancer.
AB  - It has been reported that the population of regulatory T cells (T regs) is
      increased in tumour-infiltrating lymphocytes in cancer-bearing hosts. Recently,
      forkhead/winged helix transcription factor p3, Foxp3, is thought to be the most
      reliable marker of T regs. In the present study, we investigated the prevalence
      and localisation pattern of Foxp3+ cells in gastric cancer (n=80) by
      immunohistochemistry, in relation to the clinical outcome of gastric cancer
      patients. Immunohistochemical staining was performed with anti-Foxp3 mAb, and
      Foxp3+ cells were semiquantified. We divided all cases into two groups: Foxp3+ 
      high (n=40) and Foxp3+ -low (n=40) groups, by the median size of the population
      of Foxp3+ cells. Furthermore, in terms of the localisation pattern of
      accumulating Foxp3+ cells in tumours, we classified all cases into three groups:
      a peri-tumour group (n=30), a diffuse group (n=40), and a follicular group
      (n=10). As a result, although the populations of Foxp3+ cells in stage IV were
      significantly larger than those in stage I (P<0.05), there was no significant
      difference in survival between the patients with high and low population levels
      of Foxp3+ cells. However, survival in patients with a diffuse pattern of Foxp3+
      cells was significantly poorer than in those with a peri-tumoral pattern. In
      conclusion, the localisation pattern, but not the population size, of Foxp3+
      cells was significantly related to patient survival.

PMID- 18087279
TI  - Identification of DNA hypermethylation of SOX9 in association with bladder cancer
      progression using CpG microarrays.
AB  - CpG island arrays represent a high-throughput epigenomic discovery platform to
      identify global disease-specific promoter hypermethylation candidates along
      bladder cancer progression. DNA obtained from 10 pairs of invasive bladder
      tumours were profiled vs their respective normal urothelium using differential
      methylation hybridisation on custom-made CpG arrays (n=12 288 clones). Promoter
      hypermethylation of 84 clones was simultaneously shown in at least 70% of the
      tumours. SOX9 was selected for further validation by bisulphite genomic
      sequencing and methylation-specific polymerase chain reaction in bladder cancer
      cells (n=11) and primary bladder tumours (n=101). Hypermethylation was observed
      in bladder cancer cells and associated with lack of gene expression, being
      restored in vitro by a demethylating agent. In primary bladder tumours, SOX9
      hypermethylation was present in 56.4% of the cases. Moreover, SOX9
      hypermethylation was significantly associated with tumour grade and overall
      survival. Thus, this high-throughput epigenomic strategy has served to identify
      novel hypermethylated candidates in bladder cancer. In vitro analyses supported
      the role of methylation in silencing SOX9 gene. The association of SOX9
      hypermethylation with tumour progression and clinical outcome suggests its
      relevant clinical implications at stratifying patients affected with bladder
      cancer.

PMID- 18087280
TI  - Comprehensive epidermal growth factor receptor gene analysis from cytological
      specimens of non-small-cell lung cancers.
AB  - Epidermal growth factor receptor (EGFR) gene mutations and increased copy numbers
      are considered as predictors of response to EGFR tyrosine kinase inhibitors (EGFR
      TKI) in non-small-cell lung cancer (NSCLC). Lung cancer diagnosis is often based
      on cytology alone. However, almost all published data on EGFR gene analyses were
      obtained from biopsies. This study tested the feasibility of EGFR gene analyses
      on cytological specimens. Eighty-four cytological specimens from NSCLCs were
      prospectively analysed for EGFR gene mutation in exons 18-21 and EGFR gene copy
      numbers were evaluated by fluorescence in situ hybridisation (FISH). A FISH
      positive result was defined according to the criteria by Cappuzzo et al
      established for biopsies of NSCLCs. Fluorescence in situ hybridisation results of
      cytological specimens were compared to the FISH results on matching biopsies
      (n=33). Initial diagnosis of NSCLC was solely based on cytology in 37 out of 84
      (44.0%) patients. Out of 80 NSCLCs, 6 (7.5%) showed EGFR gene mutations. Out of
      67 cancers, 45 (67.2%) were FISH positive on cytological specimens. Comparison of
      FISH showed a FISH-positive result in 21 out of 33 (63.6%) cytological specimens
      but in only 8 out of 33 (24.2%) matched biopsies. Epidermal growth factor
      receptor gene analyses are well applicable to cytological specimens. The high
      FISH-positive rate of NSCLC on cytological specimens contrasts with the low rate
      on biopsies when previously suggested criteria are used. New criteria for a
      positive EGFR FISH status to predict response to therapy with EGFR-TKI need to be
      defined for cytological specimens.

PMID- 18087282
TI  - Possible protective effect of green tea intake on risk of adult leukaemia.
AB  - In a case-control study of 107 adults with leukaemia and 110 orthopaedic controls
      in China, a reduced risk was found with longer duration, higher quantity, and
      frequency of green tea intake.

PMID- 18087281
TI  - Childhood leukaemia and population movements in France, 1990-2003.
AB  - In a national study, we investigated the incidence of childhood leukaemia (CL)
      over a 14-year period in France in relation to several measures based on the
      proportion of individuals who changed address between the last two national
      censuses. A positive association was found with the proportion of migrants who
      came from a distant place. The further the migrants came, the higher was the
      incidence of leukaemia, particularly among children aged 0-4 years in 'isolated'
      communes at the time of diagnosis (RR=1.4, 95% CI: 1.1,1.8 in the highest
      category of migration distance). Although the role of the population density was
      less obvious, a more marked association was found above a certain threshold. No
      association with the proportion of commuters was observed.

PMID- 18087283
TI  - Antitumour effect of polyoxomolybdates: induction of apoptotic cell death and
      autophagy in in vitro and in vivo models.
AB  - Polyoxomolybdates (PMs) as discrete molybdenum-oxide cluster anions have been
      investigated in the course of study of their medical applications. Here, we show
      the significant antitumour potency of the polyoxomolybdate
      [Me(3)NH](6)[H(2)Mo(V)(12)O(28)(OH)(12)(Mo(VI)O(3))(4)].2H(2)O (PM-17), which is
      a photo-reduced compound of [NH(3)Pr(i)](6)[Mo(7)O(24)].3H(2)O. The effect of PM
      17 on the growth of cancer cell lines and xenografts was assessed by a cell
      viability test and analysis of tumour expansion rate. Morphological analysis was
      carried out by Hoechst staining, flow-cytometric analysis of Annexin V staining,
      terminal deoxynucleotidyl transferase-mediated 'nick-end' labelling staining, and
      electron-microscopic analysis. Activation of autophagy was detected by western
      blotting and fluorescence-microscopic analysis of the localisation of GFP-LC3 in
      transfected tumour cells. PM-17 inhibited the growth of human pancreatic cancer
      (AsPC-1) xenografts in a nude mice model, and induced morphological alterations
      in tumour cells. Correspondingly, PM-17 repressed the proliferation of AsPC-1
      cells and human gastric cancer cells (MKN45) depending on the dose in vitro. We
      observed apoptotic patterns as the formation of apoptotic small bodies and
      translocation of phosphatidylserine by Hoechst staining and flow-cytometric
      analysis following Annexin V staining, and in parallel, autophagic conformation
      by the formulation of autophagosomes and localisation of GFP-LC3 by electron- and
      fluorescence-microscopic analysis.

PMID- 18087284
TI  - Biological predictive factors in rectal cancer treated with preoperative
      radiotherapy or radiochemotherapy.
AB  - We analysed the expression of microsatellite instability, p53, p21, vascular
      endothelial growth factor and thymidylate synthase (TS) in pretreatment biopsy
      specimens from 57 locally advanced rectal cancers. The aim of the study was to
      correlate the expression of these markers with pathological response. Nineteen
      patients were treated with preoperative concomitant radiotherapy (RT) and
      fluorouracil/oxaliplatin-based chemotherapy (RCT), while 38 had RT alone.
      Pathological complete remission (pCR) and microfoci residual tumour (micR)
      occurred more frequently in patients treated with RCT (P=0.002) and in N0 tumours
      (P=0.004). Among patients treated with RCT, high TS levels were associated with a
      higher response rate (pCR+micR; P=0.015). No such correlation was found in the RT
      group. The other molecular factors were of no predictive value. Multivariate
      analysis confirmed a significant interaction between nodal status and the
      probability of achieving a pathological response (P=0.023) and between TS
      expression and treatment, indicating that a high TS level is predictive of a
      higher pathological response in the RCT subset (P=0.007). This study shows that
      lymph node status is the most important predictive factor of tumour response to
      preoperative treatment. Thymidylate synthase expression assessed
      immunohistochemically from pretreatment tumour biopsies may be a useful
      predictive marker of rectal tumour response to preoperative RCT.

PMID- 18087285
TI  - Clinicopathological and prognostic significance of EGFR, VEGF, and HER2
      expression in cholangiocarcinoma.
AB  - Epidermal growth factor receptor (EGFR), vascular endothelial growth factor
      (VEGF), and human epidermal growth factor receptor 2 (HER2) have been considered
      as potential therapeutic targets in cholangiocarcinoma, but no studies have yet
      clarified the clinicopathological or prognostic significance of these molecules.
      Immunohistochemical expression of these molecules was assessed retrospectively in
      236 cases of cholangiocarcinoma, as well as associations between the expression
      of these molecules and clinicopathological factors or clinical outcome. The
      proportions of positive cases for EGFR, VEGF, and HER2 overexpression were 27.4,
      53.8, and 0.9% in intrahepatic cholangiocarcinoma (IHCC), and 19.2, 59.2, and
      8.5% in extrahepatic cholangiocarcinoma (EHCC), respectively.
      Clinicopathologically, EGFR overexpression was associated with macroscopic type
      (P=0.0120), lymph node metastasis (P=0.0006), tumour stage (P=0.0424), lymphatic
      vessel invasion (P=0.0371), and perineural invasion (P=0.0459) in EHCC, and VEGF
      overexpression with intrahepatic metastasis (P=0.0224) in IHCC. Multivariate
      analysis showed that EGFR expression was a significant prognostic factor (hazard
      ratio (HR), 2.67; 95% confidence interval (CI), 1.52-4.69; P=0.0006) and also a
      risk factor for tumour recurrence (HR, 1.89; 95% CI, 1.05-3.39, P=0.0335) in
      IHCC. These results suggest that EGFR expression is associated with tumour
      progression and VEGF expression may be involved in haematogenic metastasis in
      cholangiocarcinoma.

PMID- 18087286
TI  - Breast cancer risk factors and a novel measure of volumetric breast density:
      cross-sectional study.
AB  - We conducted a cross-sectional study nested within a prospective cohort of breast
      cancer risk factors and two novel measures of breast density volume among 590
      women who had attended Glasgow University (1948-1968), replied to a postal
      questionnaire (2001) and attended breast screening in Scotland (1989-2002).
      Volumetric breast density was estimated using a fully automated computer
      programme applied to digitised film-screen mammograms, from medio-lateral oblique
      mammograms at the first-screening visit. This measured the proportion of the
      breast volume composed of dense (non-fatty) tissue (Standard Mammogram Form
      (SMF)%) and the absolute volume of this tissue (SMF volume, cm3). Median age at
      first screening was 54.1 years (range: 40.0-71.5), median SMF volume 70.25 cm3
      (interquartile range: 51.0-103.0) and mean SMF% 26.3%, s.d.=8.0% (range: 12.7
      58.8%). Age-adjusted logistic regression models showed a positive relationship
      between age at last menstrual period and SMF%, odds ratio (OR) per year later:
      1.05 (95% confidence interval: 1.01-1.08, P=0.004). Number of pregnancies was
      inversely related to SMF volume, OR per extra pregnancy: 0.78 (0.70-0.86,
      P<0.001). There was a suggestion of a quadratic relationship between birthweight
      and SMF%, with lowest risks in women born under 2.5 and over 4 kg. Body mass
      index (BMI) at university (median age 19) and in 2001 (median age 62) were
      positively related to SMF volume, OR per extra kg m(-2) 1.21 (1.15-1.28) and 1.17
      (1.09-1.26), respectively, and inversely related to SMF%, OR per extra kg m(-2)
      0.83 (0.79-0.88) and 0.82 (0.76-0.88), respectively, P<0.001. Standard Mammogram
      Form% and absolute SMF volume are related to several, but not all, breast cancer
      risk factors. In particular, the positive relationship between BMI and SMF volume
      suggests that volume of dense breast tissue will be a useful marker in breast
      cancer studies.

PMID- 18087287
TI  - Timing of breast cancer surgery in relation to menstrual cycle phase: no effect
      on 3-year prognosis: the ITS Study.
AB  - The effect of breast cancer surgery timing during the menstrual cycle on
      prognosis remains controversial. We conducted a multicentre prospective study to
      establish whether timing of interventions influences prognosis. We report 3-year
      overall and disease-free survival (OS/DFS) results for 'primary analysis'
      patients (regular cycles, no oral contraceptives within previous 6 months). Data
      were collected regarding timing of interventions in relation to patients' last
      menstrual period (LMP) and first menstrual period after surgery (FMP). Hormone
      profiles were also measured. Cox's proportional hazards model incorporated LMP in
      continuous form. Exploratory analyses used menstrual cycle categorisations of
      Senie, Badwe and Hrushesky. Hormone profiles with LMP and FMP data were also used
      to define menstrual cycle phase. Four hundred and twelve 'primary analysis'
      patients were recruited. Three-year OS from first surgery was 90.7, 95%
      confidence interval (CI) [87.9, 93.6%]. Menstrual cycle according to LMP was not
      statistically significant (OS: hazard ratio (HR)=1.02, 95%CI [0.995,1.042],
      P=0.14; DFS: HR=1.00, 95%CI [0.980,1.022], P=0.92). Timing of surgery in relation
      to menstrual cycle phase had no significant impact on 3-year survival. This may
      be due to 97% of patients receiving some form of adjuvant therapy. Survival
      curves to 10 years indicate results may remain true for longer-term survival.

PMID- 18087288
TI  - Reply: Expression of the proteolysis-inducing factor core-peptide mRNA is
      upregulated in both tumour and adjacent normal tissue in gastrooesophageal
      malignancy.

PMID- 18087289
TI  - Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as
      salvage chemotherapy for patients with advanced or metastatic transitional cell
      carcinoma after failure of gemcitabine and cisplatin chemotherapy.
AB  - We investigated the safety and efficacy of a methotrexate, vinblastine,
      doxorubicin and cisplatin (M-VAC) combination regimen as second-line chemotherapy
      for patients with advanced or metastatic transitional cell carcinoma who failed
      first-line gemcitabine and cisplatin (GC) chemotherapy. Thirty patients who had
      progressed or relapsed after GC chemotherapy as first-line treatment were
      enrolled in this study. The major toxicities were neutropaenia and
      thrombocytopaenia. A grade 3 or 4 neutropaenia occurred in 19 (63.3%) and a grade
      3 or 4 thrombocytopaenia developed in nine patients (30.0%). There were no life
      threatening complications during the study. The overall response was 30%. A
      complete response was achieved in two patients (6.7%) and a partial response in
      seven (23.3%). The overall disease control rate was 50%. Seven out of 16 patients
      who had responded previously to GC responded to M-VAC, while 2 out of 14 who had
      not responded to GC responded to M-VAC. The median response duration was 3.9
      months and the median progression-free survival was 5.3 months. The median
      overall survival was 10.9 months. M-VAC showed encouraging efficacy and
      reversible toxicities in patients who had progressed after GC chemotherapy and,
      especially, M-VAC appears to be a reasonable option as a sequential treatment
      regimen in patients who responded previously to GC chemotherapy.

PMID- 18087290
TI  - DNA damage-induced cell death: lessons from the central nervous system.
AB  - DNA damage can, but does not always, induce cell death. While several pathways
      linking DNA damage signals to mitochondria-dependent and -independent death
      machineries have been elucidated, the connectivity of these pathways is subject
      to regulation by multiple other factors that are not well understood. We have
      proposed two conceptual models to explain the delayed and variable cell death
      response to DNA damage: integrative surveillance versus autonomous pathways. In
      this review, we discuss how these two models may explain the in vivo regulation
      of cell death induced by ionizing radiation (IR) in the developing central
      nervous system, where the death response is regulated by radiation dose, cell
      cycle status and neuronal development.

PMID- 18087291
TI  - The DNA damage response pathways: at the crossroad of protein modifications.
AB  - Post-translational modifications play a crucial role in coordinating cellular
      response to DNA damage. Recent evidence suggests an interplay between multiple
      protein modifications, including phosphorylation, ubiquitylation, acetylation and
      sumoylation, that combine to propagate the DNA damage signal to elicit cell cycle
      arrest, DNA repair, apoptosis and senescence. Utility of specific post
      translational modifiers allows temporal and spatial control over protein
      relocalization and interactions, and may represent a means for trans-regulatory
      activation of protein activities. The ability to recognize these specific
      modifiers also underscores the capacity for signal amplification, a crucial step
      for the maintenance of genomic stability and tumor prevention. Here we have
      summarized recent findings that highlight the complexity of post-translational
      modifications in coordinating the DNA damage response, with emphasis on the DNA
      damage signaling cascade.

PMID- 18087292
TI  - Flexibility in the order of action and in the enzymology of the nuclease,
      polymerases, and ligase of vertebrate non-homologous DNA end joining: relevance
      to cancer, aging, and the immune system.
AB  - Nonhomologous DNA end joining (NHEJ) is the primary pathway for repair of double
      strand DNA breaks in human cells and in multicellular eukaryotes. The causes of
      double-strand breaks often fragment the DNA at the site of damage, resulting in
      the loss of information there. NHEJ does not restore the lost information and may
      resect additional nucleotides during the repair process. The ability to repair a
      wide range of overhang and damage configurations reflects the flexibility of the
      nuclease, polymerases, and ligase of NHEJ. The flexibility of the individual
      components also explains the large number of ways in which NHEJ can repair any
      given pair of DNA ends. The loss of information locally at sites of NHEJ repair
      may contribute to cancer and aging, but the action by NHEJ ensures that entire
      segments of chromosomes are not lost.

PMID- 18087293
TI  - Research ethics and the challenge of whole-genome sequencing.
AB  - The recent completion of the first two individual whole-genome sequences is a
      research milestone. As personal genome research advances, investigators and
      international research bodies must ensure ethical research conduct. We identify
      three major ethical considerations that have been implicated in whole-genome
      research: the return of research results to participants; the obligations, if
      any, that are owed to participants' relatives; and the future use of samples and
      data taken for whole-genome sequencing. Although the issues are not new, we
      discuss their implications for personal genomics and provide recommendations for
      appropriate management in the context of research involving individual whole
      genome sequencing.

PMID- 18087294
TI  - Does androgen deprivation therapy in men with prostate cancer increase
      cardiovascular morbidity?

PMID- 18087295
TI  - Gene therapy for the treatment of erectile dysfunction.

PMID- 18087296
TI  - Are nursing-home residents at high risk of warfarin-related complications?

PMID- 18087297
TI  - A new continuous-flow LV assist device for patients with end-stage heart failure.

PMID- 18087298
TI  - Is dronedarone effective for the prevention of recurrent atrial fibrillation?

PMID- 18087299
TI  - Is the FIBROSpect II index effective for determining the stage of fibrosis in
      patients with chronic hepatitis C?

PMID- 18087301
TI  - Multifocal multiphoton microscopy.
AB  - We present a real-time, direct-view multiphoton excitation fluorescence
      microscope that provides three-dimensional imaging at high resolution. Using a
      rotating microlens disk, we split the near-infrared light of a mode-locked
      titanium-sapphire laser into an array of beams that are transformed into an array
      of high-aperture foci at the object. We typically scan at 225 frames per second
      and image the fluorescence with a camera that reads out the images at video rate.
      For 1.4 aperture oil and 1.2 water immersion lenses at 780-nm excitation we
      obtained axial resolutions of 0.84 and 1.4mum , respectively, which are similar
      to that of a single-beam two-photon microscope. Compared with the latter setup,
      our system represents a 40-100-fold increase in efficiency, or imaging speed.
      Moreover, it permits the observation with the eye of high-resolution two-photon
      images of (live) samples.

PMID- 18087300
TI  - Is biofeedback therapy an effective treatment for dyssynergic defecation?

PMID- 18087302
TI  - Tomographic identification of gas bubbles in two-phase flows with the combined
      use of the algebraic reconstruction technique and the genetic algorithm.
AB  - Combined use of the algebraic reconstruction technique (ART) and the genetic
      algorithm (GA) shows highly accurate and efficient tomographic reconstruction of
      line-of-sight projection images of two-phase flows compared with reconstructions
      obtained by separate use of these methods. A modified GA-based tomography uses
      the ART reconstruction result as preliminary information on the number, shapes,
      and sizes of bubbles to be reconstructed. This combined use of the two methods
      exploits faster convergence of the ART to the approximate solution space and more
      robust and accurate optimization of the GA to the ultimate solution space. In the
      investigation a computer-synthesized phantom field that consisted of five
      elliptical gas bubbles in liquid or solid surroundings was used.

PMID- 18087303
TI  - Diffusion-bonded stacks of periodically poled lithium niobate.
AB  - We constructed diffusion-bonded stacks of periodically poled lithium niobate
      (PPLN). Such crystals combine the advantages of planar processing used to make
      PPLN wafers with the power-handling capability of large apertures. We
      demonstrated an optical parametric oscillator that uses a 3-mm-thick diffusion
      bonded stack consisting of three 1-mm-thick PPLN crystals.

PMID- 18087304
TI  - High-power synchronously pumped AgGaS(2) optical parametric oscillator.
AB  - Greater than 2 W of average power was generated in the infrared region by a
      AgGaS(2) optical parametric oscillator (OPO). A Q -switched mode-locked laser was
      used to pump the OPO synchronously. Tunability from 1.4 to 1.9mum and a maximum
      output power of 750 mW at 1.44mum were achieved with a standing-wave cavity.
      Redesigning the cavity into a ring configuration allowed the depleted pump,
      signal, and idler beams to be extracted efficiently through separate mirrors.
      This design generated signal and idler beams of high spatial quality at
      respective power levels of 1.5 and 620 mW at a pulse repetition rate of 2 kHz.

PMID- 18087305
TI  - Stabilization of dark and vortex parametric spatial solitons.
AB  - We demonstrate that a weak defocusing Kerr effect in an optical medium with
      predominantly quadratic [or chi((2))] nonlinear response can eliminate the
      parametric modulational instability of plane waves, leading to the existence of
      stable two-wave dark and vortex spatial solitons.

PMID- 18087306
TI  - Lateral patterning of nonlinear frequency conversion with transversely varying
      quasi-phase-matching gratings.
AB  - We demonstrate control of the nonlinear conversion across a beam profile by using
      periodically poled lithium niobate with a laterally nonuniform quasi-phase
      matching grating. As a representative experiment, generation of a flat-top second
      harmonic beam is demonstrated.

PMID- 18087307
TI  - Simultaneous measurement of amplitude and phase in surface second-harmonic
      generation.
AB  - The intensity and the phase in surface second-harmonic generation were
      simultaneously measured by use of an ac optical balanced homodyne detection
      system. In this system the surface second-harmonic wave was superimposed upon a
      local oscillator wave generated by a barium borate nonlinear optical crystal and
      then detected as an interference signal. Extremely high sensitivity of 3 aW (6
      photons/s) and high precision were achieved by use of a lock-in amplifier, in
      which an interference signal of fundamental waves was used as a reference signal.
      Simultaneous measurement of the intensity and the phase in surface second
      harmonic waves generated from native-oxidized Si(111) surfaces is demonstrated.

PMID- 18087308
TI  - Direct measurement of self-phase shift due to fiber nonlinearity.
AB  - We directly measure the time-independent nonlinear self-phase shift of a pulse
      after fiber propagation by spectral interferometry. Both the soliton and the
      nonsoliton case were studied. We verify numerically that the measured phase shift
      approximates this time-independent phase well.

PMID- 18087310
TI  - Polarization mode dispersion induced pulse broadening in optical fibers.
AB  - A simple and exact analytical expression is derived for the amount of broadening
      that a pulse suffers when it is subjected to the combined actions of polarization
      mode dispersion, chromatic dispersion, and chirping. The theory is then applied
      to various manifestations of second-order polarization mode dispersions.

PMID- 18087309
TI  - Dispersion-managed solitons in optical amplifier transmission systems with zero
      average dispersion.
AB  - Soliton propagation in a cascaded dispersion-managed optical amplifier system
      with zero net dispersion is examined. We present a qualitative physical
      explanation for the recently discovered fact that a soliton with finite energy
      can propagate down a fiber line with zero or normal average dispersion. We
      describe a specific practical system for the main properties of such a soliton,
      namely, the dependence of the soliton power on the pulse width at chirp-free
      points and the soliton average energy and width at chirp-free points as functions
      of the dispersion-allocation (strength of the map) parameter.

PMID- 18087312
TI  - Analysis of Gordon-Haus jitter in a dispersion-compensated optical transmission
      system.
AB  - We theoretically analyzed the Gordon-Haus timing jitter in a periodically
      dispersion-compensated optical transmission system as a result of upgrading a
      preinstalled uniform-dispersion system. We show that the enhanced peak power for
      a large dispersion difference in the period reduces the frequency shift induced
      by noise, and a proper setting of the receiver position further reduces the
      timing jitter.

PMID- 18087311
TI  - Direct measurement of electrostriction in optical fibers.
AB  - The electrostriction contribution to the nonlinear refractive index in optical
      fiber was theoretically calculated and measured. Nonlinearity was induced
      directly by insertion of the optical fiber into an intense external electric
      field. With this technique both the Kerr and the electrostrictive contributions
      to the intensity dependence of the nonlinear refractive index in a step-index
      fiber were measured. Good agreement between calculated and measured values was
      observed. These results should confirm and explain the differences observed in
      measurement of n(2) at different bit rates.

PMID- 18087313
TI  - Complex photosensitivity observed in germanosilica planar waveguides.
AB  - Photosensitive effects distinguished as type I and type IIA photosensitivity
      within optical fibers were observed in a much more pronounced form within
      germanosilica waveguides deposited by hollow-cathode plasma-enhanced chemical
      vapor deposition. With increasing exposure to 193-nm UV light, positive index
      changes greater than 2 x 10(-3) were observed, followed by negative index changes
      greater than -5 x 10(-3) . These behaviors are attributed to an increase in
      macroscopic polarizability and a reduction in material density, respectively. The
      negative index change is more temperature resistant and is fully annealed only at
      900 degrees C, whereas the positive one is annealed at 500 degrees C.

PMID- 18087314
TI  - Normal-incidence guided-mode resonant grating filters: design and experimental
      demonstration.
AB  - Guided-mode resonant grating filters have numerous applications. However, in
      weakly modulated gratings designed for use at normal incidence, the filtering
      resonance of these subwavelength-period devices splits for angles of incidence
      that are even slightly off normal incidence. Strongly modulated gratings are
      designed that essentially overcome this practical problem near normal incidence.
      In addition, these gratings can have, by design, either broad or narrow spectral
      characteristics. An experimental demonstration (1.5-2.0-mu m wavelength range) of
      such a normal-incidence guided-mode resonant silicon grating upon a sapphire
      substrate is presented. The measured reflection resonance had a FWHM of 67-100 nm
      for angles of incidence of 0-8 degrees and peak efficiency of ~80% .

PMID- 18087315
TI  - Controlling lasers by use of extended time-delay autosynchronization.
AB  - A method is described for suppressing chaotic instabilities in lasers by use of a
      specific form of controlling-chaos feedback. The technique is easy to implement
      and requires only application of small perturbations to an accessible system
      parameter or variable.

PMID- 18087316
TI  - Enhanced performance of elemental copper-vapor lasers by use of H(2)-HCl-Ne
      buffer-gas mixtures.
AB  - The output power from a 25-mm-diameter (volume, 0.49 L) and a 40-mm-diameter
      (volume, 1.9 L) copper-vapor laser (nominally 20- and 65-W devices, respectively)
      was approximately doubled to >50 and >100 W , respectively, by addition of small
      partial pressures of both H(2) and HCl to the neon buffer gas. The specific
      output powers of these lasers are believed to be records for any copper-vapor
      lasers of this size.

PMID- 18087317
TI  - Programmable phase control of femtosecond pulses by use of a nonpixelated spatial
      light modulator.
AB  - Programmable spectral phase modulation of femtosecond pulses by use of a
      nonpixelated spatial light modulator is reported. This light valve, based on the
      optical addressing of a continuous layer of liquid crystal, allows the operation
      of spectral phase modulation when optical frequency components are spatially
      dispersed within a grating-and-lenses pulse-shaping apparatus. Characterization
      and feedback control of this device were determined by use of spectral
      interferometry. Demonstrations of the capabilities of this device are given in
      the spectral and the temporal domains, and recompression of chirped pulses was
      performed.

PMID- 18087318
TI  - Femtosecond quadrature-squeezed light generation in CdSe at 1.55 mum.
AB  - We generated pulsed quadrature-squeezed light by cross-phase modulation in single
      crystal hexagonal CdSe at wavelengths of 1.4 to 1.55mum . We measured 0.4-dB
      squeezing (0.7 dB is inferred at the crystal) with 100-fs laser pulses. The
      wavelength and the intensity dependence, as well as variations in the local
      oscillator configuration, are examined. At higher intensities squeezing is shown
      to deteriorate owing to competing nonlinear processes.

PMID- 18087319
TI  - Period doubling of a femtosecond Ti:sapphire laser by total mode locking.
AB  - Period doubling of an 84-MHz repetition-rate Kerr-lens mode-locked Ti:sapphire
      laser operated at 830 nm and producing ~300mW of average power has been observed
      and explained in terms of total mode locking of TEM(00) and TEM(01) modes in an
      effective confocal cavity. This configuration leads to a spatial sweeping action
      of a single-peaked pulse at 42 MHz. Period tripling and quadrupling is observed
      for certain cavity configurations.

PMID- 18087320
TI  - Thermal eigenmode amplifiers for diffraction-limited amplification of ultrashort
      pulses.
AB  - The design of high-repetition, high-average power, multipass amplifiers in which
      the pump power induced thermal lensing within the amplifier is used to create an
      equivalent lens waveguide for the production of diffraction-limited beams is
      analyzed.

PMID- 18087321
TI  - Noise and amplitude-squeezing performance of two-polarization-mode semiconductor
      lasers.
AB  - Using a theoretical semiclassical approach, we study in detail the amplitude
      fluctuations and correlations of a two-orthogonal polarization-mode semiconductor
      laser as obtained from a vertical-cavity surface-emitting laser (VCSEL). We
      demonstrate that there exists the possibility of squeezing in the two-mode regime
      besides sub-shot-noise emission in the well-known ideal single-mode operation
      regime. These theoretical results confirm a recent experimental demonstration of
      the generation of amplitude-squeezed light with VCSEL's.

PMID- 18087322
TI  - Determination of the angular separation and the spectra of two-point sources from
      spectral coherence measurements.
AB  - We present a novel method not only for determining the angular separation of
      unknown two-point spectral sources but also for obtaining each of their spectral
      profiles from measurements of both their complex degree of spectral coherence and
      their spectra across an observation area in the space-frequency domain. The
      theoretical predictions are fully proved by an experimental demonstration with a
      pair of uncorrelated two-point spectral sources.

PMID- 18087323
TI  - Diffusion of photoexcited azo dye in a liquid-crystal host.
AB  - Dynamic holograms are created and studied in a D2 azo-dye-doped nematic liquid
      crystal. The dependence of diffraction on the excitation and probe polarizations
      is observed. The efficiency of excitation and the corresponding relaxation time
      depend also on the period and orientation of the light-interference pattern with
      respect to the initial molecular orientation. The excitation and diffusion of dye
      molecules are suggested to be the origin of these phenomena.

PMID- 18087324
TI  - Long holographic lifetimes in bacteriorhodopsin films.
AB  - The D85N genetic variant of bacteriorhodopsin (BR) displays a nearly permanent
      lifetime of the photochromic P(490) state. We present pump-probe measurements
      that demonstrate this behavior. However, diffraction efficiency measurements made
      from holograms recorded in a hydrated D85N film show markedly different decay
      behavior, suggesting that a molecular diffusion process is occurring in the film.
      Holograms recorded with different grating frequencies display correspondingly
      different decay times, thus supporting this hypothesis. A thin D85N film was
      fabricated that was chemically cross linked, resulting in the elimination of
      diffusion of BR molecules within the polymer matrix. This film exhibits a grating
      lifetime of the order of weeks or more, thus permitting the long-term holographic
      storage of information.

PMID- 18087325
TI  - Second-harmonic tomography of tissues: errata.

PMID- 18087326
TI  - Use of error diffusion with space-variant optimized weights to obtain high
      quality quantized images and holograms.
AB  - Error diffusion is an important procedure for image and hologram quantization.
      The spatial distribution of the spectrum of the quantization noise is shaped by a
      filter function, which depends on the diffusion weights. The customary weights
      applied during the whole quantization process are optimized to yield the desired
      filter functions. Stability restrictions limit the optimization process. We
      suggest optimizing new weights locally after the quantization of each pixel. In
      this way the eventual occurrence of instabilities can be counteracted and the
      quality of the filter function improved.

PMID- 18087327
TI  - Absolute sphericity measurement: a comparative study of the use of interferometry
      and a Shack-Hartmann sensor.
AB  - A comparison of absolute sphericity measurements with a ShackHartmann sensor and
      a TwymanGreen interferometer is presented. The absolute deviations of a test
      sphere from its ideal shape were calculated in both cases from the measured wave
      aberrations of three different positions. Very good qualitative and quantitative
      agreement of the results was achieved. The difference of the root-mean-square
      values of the two methods was 1/1000 of a wavelength.

PMID- 18087328
TI  - Synthetic imaging: nonadaptive anisoplanatic image correction in atmospheric
      turbulence.
AB  - We introduce a synthetic-imaging technique that can be applied to correct
      anisoplanatic images degraded by atmospheric turbulence. This method is based on
      local image-quality analysis applied to a large set of short-exposure images and
      can be considered a generalization of the frame-selection technique. Experimental
      results obtained for atmospheric data demonstrate the efficiency of the synthetic
      imaging technique in improving image quality.

PMID- 18087329
TI  - Confocal microscopy with a refractive microlens-pinhole array.
AB  - The stable setup of a confocal arrangement consisting of a combination of a
      refractive microlens and a pinhole array is presented. The focal plane of the
      microlenses lies at the rear surface of the substrate in the pinhole plane. By
      using a microscope objective one can image the stop array onto the object at a
      reduced size. Surface profiles of refractive and diffractive optical elements
      were measured with the help of this confocal microscope.

PMID- 18087330
TI  - Interference between caustics of diffraction fields.
AB  - The caustics of diffraction fields are structures that present a nonlinear phase
      distribution. The superposition of two caustics presents interesting irradiance
      distributions, which we analyze within the framework of catastrophe theory. This
      treatment permits the inclusion of the optical path difference involved in a
      parametric family, and by employing the geometric theory of diffraction we can
      analyze the interference patterns in a selective fashion. The theoretical
      predictions are verified experimentally with a Michelson interferometer.

PMID- 18087331
TI  - Method for determining the two-beam coupling gain coefficients of photorefractive
      crystals.
AB  - A new method is proposed for determining the two-beam coupling gain coefficients
      of photorefractive crystals with both o- and e-polarized lights. This method
      enables one to determine simultaneously and precisely the gain coefficients of a
      crystal for o- and e-polarized lights while the fanning effect is diminished.
      Experimental demonstrations are presented.

PMID- 18087332
TI  - Use of two-photon absorption in a photorefractive crystal for three-dimensional
      optical memory.
AB  - We describe the use of two-photon absorption in a photorefractive crystal for
      recording bit data in multilayered optical memory. A short-pulse near-infrared
      laser is used for generating the photorefractive effect by two-photon absorption.
      We succeeded in recording and reading seven layers of data in a LiNbO(3) crystal
      with a lateral resolution (distance between bits) of 5microm and an axial
      resolution (distance between layers) of 20 microm .

PMID- 18087333
TI  - Greater than 100% photon-conversion efficiency from an optical parametric
      oscillator with intracavity difference-frequency mixing.
AB  - Using 100-ps Nd:YAG pump pulses, we synchronously pump an optical parametric
      oscillator with intracavity difference-frequency mixing (DFM) between the signal
      and the idler. The cavity is singly resonant at the signal frequency. The signal,
      idler, and difference wavelengths are near 1.5, 3.5, and 2.8microm ,
      respectively. Periodically poled lithium niobate is used for both interactions.
      Results show an 80% enhancement in the idler power-conversion efficiency and an
      idler photon-conversion efficiency of 110% when the DFM interaction is phase
      matched. Backconversion of the pump is suppressed when the DFM interaction is
      phase matched, and pump depletion increases from 65% to 79% at full pump power.

PMID- 18087334
TI  - Theory of self-focusing in a hollow waveguide.
AB  - We present a theoretical investigation of self-focusing in a hollow waveguide
      filled with noble gas. Our analysis was performed for a laser pulse that was
      predominantly in the fundamental mode and revealed the physical processes
      involved in self-focusing in a hollow waveguide. A critical power for self
      focusing was obtained that was found to be substantially higher than the critical
      power for self-focusing in a bulk medium. Useful design criteria for pulse
      compression systems are presented. We identify the parameter range for which the
      transverse variation of the pulse phase introduced by the Kerr nonlinearity is
      small.

PMID- 18087335
TI  - Power enhancement with super-Gaussian sliding-frequency guiding filters.
AB  - I show with numerical simulations that higher-order sliding filters, especially
      super-Gaussian filters, can produce dramatic power enhancement of optical
      solitons, similar to that of dispersion-managed solitons. This approach should
      allow smaller timing jitter without sacrificing the signal-to-noise ratio.

PMID- 18087336
TI  - Chirped soliton interaction in strongly dispersion-managed wavelength-division
      multiplexing systems.
AB  - We theoretically analyze nonlinear interactions between chirped solitons in
      dispersion-managed wavelength-division-multiplexing (WDM) systems. We employ the
      perturbation method to evaluate frequency and chirp shifts caused by collisions
      among different WDM channels. It is shown that a chirped soliton suffers less
      frequency shift and time displacement than an ideal soliton, indicating its
      potential applicability for WDM systems.

PMID- 18087337
TI  - High-reflectivity multilayer mirrors for a vacuum-ultraviolet interval of 35
      50nm.
AB  - Sc-Si multilayers are suggested as high-reflectivity coatings for a VUV interval
      of 35-50 nm. Fabricated mirrors show normal-incidence reflectivity of 30-54%,
      which is high enough for effective manipulation of the beams of compact
      discharge, laser-driven x-ray lasers. The values obtained are not, however,
      limits for Sc-Si coatings. Theoretical estimations as well as electron microscopy
      studies of Sc-Si interfaces indicate a large potential for a further increase in
      their reflectivity.

PMID- 18087338
TI  - Simple diode pumping of a power-buildup cavity.
AB  - We have developed a novel and simple passive technique to frequency lock an
      antireflection-coated diode laser to a power-buildup cavity. The beam reflected
      from a mode-mismatched cavity is spatially filtered so the maximum reflected
      intensity occurs at a cavity resonance. We experimentally and theoretically
      investigated the locking behavior and found that it is both robust and stable. In
      an implementation of the technique a 100-W intracavity beam can be generated by
      use of only a two-mirror cavity and a 15-mW 635-nm diode laser driven by a dc
      current.

PMID- 18087339
TI  - Low-threshold lasing of a Rhodamine dye solution embedded with nanoparticle
      fractal aggregates.
AB  - The spectral and temporal emission properties of a Rhodamine (Rh) dye solution
      embedded with nanoparticle fractal aggregates are studied. An experiment on the
      pump-power density dependence of Rh emission spectra shows that the lasing
      threshold of a Rh6G solution embedded with TiO(2) nanoparticle fractal aggregates
      is significantly reduced compared with that of a neat dye solution. The mechanism
      of this reduction in lasing threshold is discussed, together with the lasing
      properties of narrow bandwidth and short duration.

PMID- 18087340
TI  - 125-mJ diode-pumped injection-seeded Ho:Tm:YLF laser.
AB  - We describe a diode-pumped, room-temperature Ho:Tm:YLF power oscillator with an
      optical-to-optical efficiency of 0.03. A Q -switched output energy of as much as
      125 mJ at 6 Hz with a pulse width of 170 ns was obtained. Single-frequency,
      nearly transform-limited operation of the laser was achieved by injection
      seeding. Laser performance as a function of laser rod temperature and pump
      intensity was also investigated. The high power and high beam quality of this
      laser make it well suited for use as a coherent wind lidar transmitter on a space
      platform.

PMID- 18087341
TI  - Three-dimensional images generated by quadrature interferometry.
AB  - Quadrature detection techniques have been applied to images obtained from a Mach
      Zehnder interferometer with differently polarized beams to yield the real and the
      imaginary parts of the diffracted fields simultaneously. This approach eliminates
      the need for phase retrieval by providing complete information on the complex
      amplitude of the diffracted signal. We present results in which we demonstrate
      our ability to reconstruct two- and three-dimensional microscopic objects from
      their complex diffraction patterns.

PMID- 18087342
TI  - Smart pixels with smart illumination.
AB  - Smart pixels with smart illumination is a new concept in sensor array technology
      based on structured built-in illumination and optoelectronic feedback. It offers
      many new possibilities and potential advantages over more-traditional sensor
      arrays. We discuss an edge-detection system as an example of how smart
      illumination can advantageously be used to achieve a variety of functions. We
      also present initial experimental results from a fabricated chip based on this
      concept. The chip includes an integrated array of photodetectors and LED's. The
      output of each pixel can be controlled based on the feedback received by its dual
      detectors.

PMID- 18087343
TI  - Continuous-wave mode-locked Ti:sapphire laser focusable to 5 x 10(13) W/cm(2).
AB  - Generation of sub-10-fs pulses with an average power of 1 W and a peak of 1.5 MW
      from a Kerr-lens mode-locked mirror-dispersion-controlled Ti:sapphire laser is
      demonstrated. A specially designed lens triplet focuses the output of this
      compact all-solid-state source to a peak intensity in excess of 5x10(13) W/cm (2)
      . Nonperturbative nonlinear optics is now becoming feasible by use of the output
      of a cw mode-locked laser.

PMID- 18087344
TI  - Spectral phase interferometry for direct electric-field reconstruction of
      ultrashort optical pulses.
AB  - We present a novel, self-referencing interferometric technique for measuring the
      amplitude and the phase of ultrashort optical pulses. The apparatus uses a
      collinear geometry that requires no moving components. The phase-retrieval
      procedure is noniterative and rapid and uses only two one-dimensional Fourier
      transforms. We apply the technique to characterize ultrashort pulses from a mode
      locked Ti:sapphire oscillator.

PMID- 18087345
TI  - Pulsed degenerate optical parametric oscillator based on a nonlinear-fiber Sagnac
      interferometer.
AB  - We report operation of an all-fiber degenerate optical parametric oscillator that
      employs a nonlinear-fiber Sagnac interferometer as a parametric amplifier.
      Synchronous pumping with 3.9-ps pulses at 1544 nm yields 0.83-ps output pulses.
      The wide bandwidth of the fiber parametric amplifier causes the oscillator to act
      as a pulse compressor. The output signal pulses exhibit improved spectral
      symmetry and a reduced time-bandwidth product compared with the pump pulses.
      Currently, the net group-velocity dispersion in the passive section of the fiber
      cavity limits the signal-pulse bandwidth and hence the minimum-obtainable pulse
      width. This experiment suggests the possibility of frequency conversion by
      operation of a similar pulsed parametric oscillator away from degeneracy.

PMID- 18087346
TI  - Femtosecond ultraviolet autocorrelation measurements based on two-photon
      conductivity in fused silica.
AB  - We utilize the two-photon conductivity of a fused-silica substrate to produce a
      photoconductive switch for use in an intensity autocorrelator for ultraviolet
      ultrashort pulses. We perform measurements at 267 nm with pulse durations in the
      range of 110-330 fs and with energies as weak as 10 nJ. Based on the bandgap of
      fused silica, this device can potentially operate in the wavelength range of 140
      280 nm.

PMID- 18087347
TI  - High-frequency enhancement by an optical system for superresolution of temporally
      restricted objects.
AB  - A system for superresolution of temporally restricted objects allows one to
      transmit ultrawideband optical signals (objects) through a narrow aperture. Such
      a system was proposed, improved, and implemented for one- and two-dimensional
      objects. Implementing frequency-plane enhancement in this system provides the
      ability of spatial filtering of ultrawideband objects. A method for spatial
      filtering in a system for superresolution of temporally restricted objects by use
      of a generalized Dammann grating is suggested. An experimental demonstration of
      high-frequency enhancement (high-pass filtering) of one-dimensional objects is
      presented.

PMID- 18087348
TI  - Nondegenerate four-wave mixing in a double-Lambda system under the influence of
      coherent population trapping.
AB  - Nondegenerate four-wave mixing (NDFWM) in a double-L system of Rb atomic vapor
      was achieved for collinear pump fields. By comparison of different pump-probe
      configurations, direct experimental evidence of influence of coherent population
      trapping on the output power of the NDFWM signal was established. A maximal
      efficiency for generating the NDFWM signal exists for a moderate pump power in
      this double-L system.

PMID- 18087349
TI  - Dichromated pullulan as a novel photosensitive holographic material.
AB  - We found that pullulan [an a -glucan with (1?4) and (1?6) linkages] doped with
      chromium ions posseses promising holographic properties. It is environmentally
      stable and is capable of registering high spatial frequencies (as many as 1500
      lines/mm) and producing surface relief. At 1000 lines/mm pullulan's diffraction
      efficiency was 4%. Chemical treatment of pullulan with a mixture of water and
      isopropyl alcohol is simple. However, as expected from analogy with dichromated
      gelatin, pullulan is sensitive in only the blue-green region of the spectrum.

PMID- 18087351
TI  - Quantitative optical phase microscopy.
AB  - We present a new method for the extraction of quantitative phase data from
      microscopic phase samples by use of partially coherent illumination and an
      ordinary transmission microscope. The technique produces quantitative images of
      the phase profile of the sample without phase unwrapping. The technique is able
      to recover phase even in the presence of amplitude modulation, making it
      significantly more powerful than existing methods of phase microscopy. We
      demonstrate the technique by providing quantitatively correct phase images of
      well-characterized test samples and show that the results obtained for more
      complex samples correlate with structures observed with Nomarski differential
      interference contrast techniques.

PMID- 18087350
TI  - Fluorescence lifetime imaging with picosecond resolution for biomedical
      applications.
AB  - We describe a novel whole-field fluorescence lifetime imaging system, based on a
      time-gated image intensifier and a solid-state laser oscillator-amplifier, that
      images lifetime differences of less than 10 ps. This system was successfully
      applied to discrimination between biological tissue constituents.

PMID- 18087352
TI  - Three-dimensional source reconstruction with a scanned pinhole camera.
AB  - We present a simple reconstruction algorithm for three-dimensional (3D)
      incoherent source distributions imaged by a laterally scanned pinhole camera. We
      consider digital sampling of multiple pinhole images for 3D reconstruction and
      implement an experimental demonstration with lateral resolution of 2x10(-3) rad
      and longitudinal resolution of approximately 0.14z(2) m , where z is the object
      to-pinhole distance in meters.

PMID- 18087353
TI  - Design of a diffractive optical element for wide spectral bandwidth.
AB  - A new method for eliminating the chromatic aberration of a diffractive optical
      element (DOE) for wideband wavelengths is presented. The wideband-wavelength
      diffractive optical element (WBDOE) consists of two aligned DOE's. The use of
      different dispersive materials for the two DOE's eliminates chromatic aberration.
      The design and simulation of a WBDOE for the visible spectrum are presented.

PMID- 18087354
TI  - Single-mode operation of a laser-diode array with frequency-selective phase
      conjugate feedback.
AB  - A new technique for single-mode operation of laser-diode arrays is presented. A
      gain-guided GaAlAs laser diode array is coupled to an external frequency
      selective phase-conjugate feedback system that contains a photorefractive barium
      titanate crystal, a Fabry-Perot etalon, and a spatial filter. The etalon is the
      key component, and it forces the array, which has low spatial and spectral
      coherence when it runs freely, to oscillate in a single spatial and a single
      longitudinal mode. At a drive current of two times the threshold current, the far
      field pattern is reduced to only 1.4 times the diffraction limit, the spectral
      bandwidth is less than 0.02 nm, and the coherence length is increased by a factor
      of 70. The technique has general validity and can be applied to various other
      multimode laser systems.

PMID- 18087355
TI  - Photorefractive shooting stars.
AB  - Under certain conditions the direction of a beam diffracted from a
      photorefractive grating wanders as the grating decays. This phenomenon is due to
      competition between the original grating and those formed spontaneously by the
      Fabry-Perot modes produced by the crystal's surfaces.

PMID- 18087356
TI  - Diode-pumped continuous-wave widely tunable optical parametric oscillator based
      on periodically poled lithium tantalate.
AB  - We report on a diode-laser pumped cw optical parametric oscillator (OPO) based on
      quasi-phase-matched periodically poled lithium tantalate. Pumped by the 2.3-W
      single-frequency, nearly diffraction-limited 925-nm output of an InGaAs diode
      master-oscillator power amplifier, the pump and signal resonant OPO generates a
      single-frequency idler wave with an output of as much as 244 mW. The wavelengths
      of the signal and idler waves are widely tunable in the range 1.55-2.3mum by use
      of different poling periods (27.3 to 27.9mum) and by variation of the crystal
      temperature in the range 70-190 degrees C.

PMID- 18087357
TI  - Phase-conjugating stimulated Brillouin scattering mirror for low powers and
      reflectivities above 90% in an internally tapered optical fiber.
AB  - A novel low-power phase-conjugating mirror based on stimulated Brillouin
      scattering in a quartz fiber with an internal taper is reported. A peak-power
      threshold as low as 500 W and a maximum reflectivity of 92% were obtained with 30
      ns pulses from a Q -switched Nd:YAG laser. The maximum peak powers of 130 kW
      demonstrated a dynamic range of 1:260. Reliable operation in both single- and
      multiple-longitudinal-mode operation was observed with conjugation fidelities
      larger than 95%.

PMID- 18087358
TI  - Continuous-wave singly resonant optical parametric oscillator based on
      periodically poled RbTiOAsO(4).
AB  - We report a continuous-wave optical parametric oscillator (OPO) based on
      periodically poled RbTiOAsO(4) (PPRTA). The singly resonant OPO, which is located
      within a Ti:sapphire laser, has a high-finesse signal cavity and delivers a
      maximum output power of 270 mW to the nonresonant idler wave at 2.92mum , through
      a 4.5-mm PPRTA crystal. For room-temperature operation and a crystal with a 30
      mu;m grating period, pump tuning over 838-848 nm results in OPO tuning over 1.13
      1.27mum (signal) and 2.53-3.26mum (idler), limited by the bandwidth of optical
      coatings. PPRTA exhibits thermal properties superior to those of periodically
      poled LiNbO(3) .

PMID- 18087359
TI  - Temperature diagnostics for cold sodium atoms by transient four-wave mixing.
AB  - Transient four-wave mixing signals were observed in cold sodium atoms. This
      phenomenon is interpreted as Bragg diffraction of a probe pulse by a population
      grating of the ground-state hyperfine level induced by pump pulses. The decay
      time of this grating is directly related to the temperature of the cold atoms and
      can serve as a novel technique for temperature diagnostics.

PMID- 18087360
TI  - Interrogation of fiber grating sensor arrays with a wavelength-swept fiber laser.
AB  - We demonstrate a novel application of a wavelength-swept fiber laser to fiber
      Bragg grating sensor-array interrogation. The laser provides high signal powers
      of >3 mW with <0.1-nm spectral resolution over a 28-nm wavelength span. Using
      time-interval counting, we demonstrate static-dynamic strain measurements with a
      resolution of 0.47mu? rms at a sampling rate of 250 Hz.

PMID- 18087361
TI  - Determination of the thermal loading of diode-pumped Nd:YVO(4) by use of
      thermally induced second-harmonic output depolarization.
AB  - A new method of using thermally induced second-harmonic output depolarization to
      determine the fractional thermal loading of a diode-pumped Nd:YVO(4) laser is
      proposed. The experimental results show that the fraction of the green output
      power polarized along the extraordinary axis of a KTP crystal, f(e) , is an
      oscillatory function of the absorbed pump power. The fractional thermal loading
      can be determined by measurement of the difference in the absorbed pump power
      between the peaks of f(e) .

PMID- 18087362
TI  - Pump geometry for resonant and quasi-resonant optical excitation of microcavity
      lasers.
AB  - A simple new pump geometry for optical excitation of microcavities and vertical
      cavity surface-emitting lasers is presented. The technique circumvents the high
      reflectivity of the cavity stop band by excitation through the substrate at a
      large angle of incidence. Under these conditions, the reflectivity of the bottom
      Bragg reflector is small, and optical pumping at any desired photon energy
      becomes possible. Experimental results for optical excitation with this new
      geometry are compared with resonant optical pumping through the cavity mode.

PMID- 18087363
TI  - Phase locking and periodic evolution of solitons in passively mode-locked fiber
      lasers with a semiconductor saturable absorber.
AB  - Passively mode-locked lasers with intracavity weakly birefringent fiber are
      theoretically analyzed based on two coupled complex one-dimensional Ginzburg
      Landau equations. The model includes fiber birefringence, spectral filtering,
      saturable gain, and saturable loss. Phase-locked soliton solutions are found for
      small amounts of birefringence and several types of soliton with periodic
      polarization evolution for higher amounts of birefringence. Numerical simulations
      show qualitative agreement with experimental results.

PMID- 18087364
TI  - Pulse-amplitude-equalized output from a rational harmonic mode-locked fiber
      laser.
AB  - We report, for the first time to our knowledge, the demonstration of amplitude
      equalization of high-repetition-rate pulses generated from a rational harmonic
      mode-locked Er-doped fiber laser. The output pulses are injected into another
      fiber laser with a nonlinear optical loop mirror. This scheme provides pulse
      amplitude equalization up to the ninth rational harmonic mode-locked pulse train.

PMID- 18087365
TI  - Measurement of cross-phase modulation in optical materials through the direct
      measurement of the optical phase change.
AB  - We measure the cross-phase modulation (XPM) nonlinear indices of optical
      materials resulting from the interaction of an ultrashort pump pulse at 800 nm
      with a weak ultrashort probe pulse at 400 nm through the direct measurement of
      the optical phase change, using frequency-resolved optical gating. The materials
      studied include fused silica (SiO(2)) , borosilicate glass (BK-7), beta-BBO , and
      KD(*)P . This method results in a XPM nonlinear index that is in agreement with
      calculations based on nonlinear indices from previous self-phase modulation
      measurements.

PMID- 18087366
TI  - Femtosecond infrared pulses tunable from 9 to 18 mum at an 88-MHz repetition
      rate.
AB  - Femtosecond mid-infrared laser pulses that are continuously tunable in the
      wavelength range from 9 to 18mum are demonstrated. These nearly bandwidth-limited
      pulses are generated by phase-matched difference-frequency mixing within the
      broad spectrum of 20-fs pulses from a mode-locked Ti:sapphire laser in GaSe. A
      direct determination of the pulse duration at 11.5mum gives a value of 140 fs.
      The average mid-infrared power of 1muW is ~100 times greater than that for
      infrared generation by non-phase-matched optical rectification.

PMID- 18087368
TI  - Generation of subpicosecond electrical pulses by optical rectification.
AB  - We describe the generation of subpicosecond electrical pulses by optical
      rectification of ultrashort optical pulses. The electrical pulses are generated
      by the second-order nonlinear response of a LiTaO(3) crystal bonded to a coplanar
      transmission line. A bipolar temporal waveform with a width of 875 fs was
      measured after a propagation distance of 175mum . This pulse width was limited by
      the response time of the photoconductive sampler. We observed both broadening and
      amplitude reduction in the temporal waveform owing to propagation.

PMID- 18087367
TI  - Engineerable femtosecond pulse shaping by second-harmonic generation with Fourier
      synthetic quasi-phase-matching gratings.
AB  - We describe a pulse-shaping technique that uses second-harmonic generation with
      Fourier synthetic quasi-phase-matching gratings. We demonstrate both amplitude
      and phase tailoring by generating a picosecond squarelike pulse as well as trains
      of femtosecond pulses with a terahertz-range repetition rate from either a
      compressed or a chirped pump pulse.

PMID- 18087369
TI  - Generation and application of twin beams from an optical parametric oscillator
      including an alpha-cut KTP crystal.
AB  - Measurement slight amounts of absorption of light with accuracy beyond the
      standard quantum limit has been experimentally demonstrated. The quantum
      correlated twin beams used in the measurement were generated from a nondegenerate
      optical parametric oscillator including an alpha-cut KTiOPO(4) crystal pumped by
      an intracavity frequency-doubled Nd:YAG laser. The noise in the intensity
      difference between the twin beams was reduced by 88% below the standard quantum
      limit (SQL). The signal-to-noise ratio was improved by 7 dB with respect to the
      SQL of the total light employed in the experiment and by 4 dB with respect to
      that of the signal light.

PMID- 18087370
TI  - Simultaneous measurement of multichannel laser linewidths and spacing by use of
      stimulated Brillouin scattering in optical fiber.
AB  - A novel method for measuring the linewidth of each laser and channel spacing in a
      multichannel transmission system is presented. Using the dependence of the Stokes
      frequency shift on the pump wavelength in stimulated Brillouin scattering, we are
      able to construct a delayed self-heterodyne interferometer that can measure the
      linewidths and channel spacing simultaneously.

PMID- 18087371
TI  - Multilevel diffractive microlens fabrication by one-step laser-assisted chemical
      etching upon high-energy-beam sensitive glass.
AB  - A new technique of laser-assisted single-step chemical etching for diffractive
      microlens fabrication upon high-energy-beam sensitive glass is reported. Laser
      direct writing with calibrated writing parameters results in gray-level mask
      patterns upon the ion-exchanged layer of the glass. The transmittance-dependent
      chemical etching upon the glass is then effectively utilized to yield suitable
      surface relief structures for multiple-phase-level diffractive optical elements.
      The one-step nonphotolithographic fabrication technique has been successfully
      applied for the realization of an eight-phase-level diffractive microlens.

PMID- 18087372
TI  - Acoustically modulated speckle imaging of biological tissues.
AB  - A video laser speckle imaging technique yields images with contrast based on the
      mechanical properties of a tissue. Fluctuations of laser speckle patterns induced
      by acoustically driving the tissue at various frequencies in the 0-30-Hz range
      encode the mechanical strain of the tissue. At each acoustic frequency and within
      the camera acquisition time, each camera pixel integrates a temporally
      fluctuating speckle intensity whose variance encodes the mechanical strain in
      response to the acoustic modulation. The magnitude and the frequency dependence
      of this strain provide mechanical information about the tissue and are the
      contrast mechanism for images.

PMID- 18087373
TI  - Nonuniqueness in diffusion-based optical tomography.
AB  - A condition on nonuniqueness in optical tomography is stated. The main result
      applies to steady-state (dc) diffusion-based optical tomography, wherein we
      demonstrate that simultaneous unique recovery of diffusion and absorption
      coefficients cannot be achieved. A specific example of two images that give
      identical dc data is presented. If the refractive index is considered an unknown,
      then nonuniqueness also occurs in frequency-domain and time-domain optical
      tomography, if the underlying model of the diffusion approximation is employed.

PMID- 18087374
TI  - Interference patterns of scattering light induced by orientational fluctuations
      in an electric-field-biased nematic liquid-crystal film.
AB  - A new light-scattering phenomenon from a planar aligned nematic liquid-crystal
      film is observed and studied. This new phenomenon exhibits ring patterns in the
      orthogonal polarization. A simple model based on optical interference has been
      developed, and its predictions agree well with experimental observation.

PMID- 18087375
TI  - Track changing by use of the phase response of microspheres and resonators.
AB  - A microsphere or resonator that is side coupled to an incident optical beam
      induces a phase response in the beam. In the so-called overcoupled regime, the
      amplitude of the incident beam remains unmodulated, whereas the phase goes
      through a shift of p at resonance. This shift is insensitive to the details of
      the coupling geometry or the resonant mode. In conjunction with an
      interferometer, the phase response can be used to switch the beam between two
      well-defined outputs, thus offering a robust means of deploying microspheres and
      other microresonators in practical photonic devices.

PMID- 18087376
TI  - Primarily isotropic nature of photorefractive screening solitons and the
      interactions between them.
AB  - We present experimental evidence demonstrating that the photorefractive-index
      change responsible for the formation of photorefractive spatial screening
      solitons and coherent collisions between them is primarily isotropic in nature,
      even though the photorefractive medium is inherently anisotropic.

PMID- 18087377
TI  - Power dependence of dispersion-managed solitons for anomalous, zero, and normal
      path-average dispersion.
AB  - We determine the power dependence of dispersion-managed solitons on map strength
      and average dispersion, using a combination of numerical simulations and the
      variational approach. In particular, we investigate the behavior near zero
      dispersion and identify the region of existence of dispersion-managed solitons in
      the average normal-dispersion regime.

PMID- 18087378
TI  - Adiabatic shaping of quadratic solitons.
AB  - We show the principle of operation of a setup to adiabatically shape solitons in
      quadratic nonlinear media to different beam profiles and widths or different
      fractions of energy carried by the second-harmonic wave. The shaping mechanism is
      based on soliton generation and propagation in chirped, quasi-phase-matched
      samples.

PMID- 18087379
TI  - Transmission reflection anomaly in second-harmonic generation from a monolayer.
AB  - We show experimentally that in second-harmonic generation from a monolayer the
      radiation propagating in transmission and that in reflection can have very
      different magnitudes. The origin of this difference lies in destructive and
      constructive interference of the components of the nonlinear polarization that
      drive the field at the second-harmonic frequency.

PMID- 18087380
TI  - Electro-optical characterization of a 2-cyclo-octylamino-5-nitropyridine thin
      organic crystal film.
AB  - 2-cyclo-octylamino-5-nitropyridine (COANP) single crystals were grown between
      transparent plates coated with indium tin oxide. The Pockels effect of the
      crystals was analyzed by an ac modulation method. The figure of merit of electro
      optic phase retardation of the COANP crystals is estimated to be 4.2x10(-12) m/V
      . The crystals were protected by the plates, and the figure of merit of the phase
      retardation of the crystals did not decrease with time. We believe that the
      crystal-growth method described is applicable to other organic compounds whose
      crystal growth from a melt is feasible.

PMID- 18087381
TI  - Self-focusing and self-trapping in unbiased centrosymmetric photorefractive
      media.
AB  - We predict self-focusing and self-trapping of optical beams propagating in
      unbiased centrosymmetric photorefractive crystals in the near-transition
      paraelectric phase, where the nonlinear response is proportional to the square of
      the diffusion space-charge field.

PMID- 18087382
TI  - Nonvolatile photorefractive spectral holography.
AB  - We demonstrate nonvolatile storage of femtosecond pulses in a photorefractive
      LiNbO(3) crystal with recording and readout of spectral holograms at wavelengths
      of 460 and 920 nm, respectively. No degradation was observed after 24 h of
      continuous readout. We also show that we can realize the time-lens effect with
      our system by appropriately setting the ratio of the recording and the
      reconstruction wavelengths and the spectral resolution of the recording and the
      reconstruction processes.

PMID- 18087383
TI  - Reflected fourth-harmonic radiation from a centrosymmetric crystal.
AB  - We present measurements of fourth-harmonic generation in reflection from the
      interface between two centrosymmetric media [Si(001)- SiO(2)] , using femtosecond
      pulses well below damage threshold. Analyses of signal amplitudes, rotational
      anisotropy, and sensitivity to surface roughening reveal that the surface dipole
      fourth-harmonic contribution dominates the bulk quadrupole contribution much more
      strongly than for second-harmonic generation.

PMID- 18087384
TI  - Observation of bright spatial photorefractive solitons in a planar strontium
      barium niobate waveguide.
AB  - We have obtained stationary bright spatial solitons in a planar photorefractive
      strontium barium niobate waveguide for visible light ranging from 514.5 to 780
      nm. Even for larger wavelengths (lambda=1047 nm) strong self-focusing of the beam
      was observed; however, input power had to be some orders of magnitude higher than
      for visible light for self-focusing to occur. Furthermore, we found transient
      self-trapping of red light (lambda=632.8 nm) that corresponds to the formation of
      bright quasi-steady-state solitons.

PMID- 18087385
TI  - Optically induced photovoltaic self-defocusing-to-self-focusing transition.
AB  - We show theoretically and experimentally that the photovoltaic nonlinearity that
      gives rise to spatial solitons can be switched from self-defocusing to self
      focusing (or vice versa) by use of background illumination. This raises the
      possibility of bright photovoltaic solitons in LiNbO(3) .

PMID- 18087386
TI  - Demonstration of the dual-tripler scheme for increased-bandwidth third-harmonic
      generation.
AB  - The dual-tripler scheme for enhancing the bandwidth of third-harmonic generation
      proposed by Eimerl et al. [Opt. Lett. 22, 1208 (1997)] is experimentally
      demonstrated for the conversion of 1054-nm radiation to 351 nm. It is shown that
      the spacing between the triplers must be carefully controlled. The results are in
      excellent agreement with theory and indicate that fusion lasers can be frequency
      tripled with a threefold increase in bandwidth.

PMID- 18087387
TI  - Timing-jitter reduction in a dispersion-managed soliton system.
AB  - We found by using Monte Carlo simulations that the timing jitter in a dispersion
      managed soliton system decreases as the strength of the dispersion management and
      hence the ratio of the pulse energy to the pulse bandwidth increases. The results
      are in qualitative but not quantitative agreement with earlier predictions that
      the decrease is inversely proportional to the square root of the pulse energy.
      Using an improved semi-analytical theory, we obtained quantitative agreement with
      the simulations.

PMID- 18087388
TI  - High-reflectivity fiber-optic bandpass filter designed by use of the iterative
      solution to the Gel'fand-Levitan-Marchenko equations.
AB  - A fiber Bragg grating bandpass filter has been investigated. The profile of the
      3.1-cm-long grating was synthesized for high reflectivity and low dispersion by
      use of the iterative solution to the Gel'fand-Levitan-Marchenko equations. A
      grating designed according to this synthesis was written into a boron-codoped
      germanosilica fiber. The measured spectral response was in good agreement with
      simulations. The achieved in-band reflection was 97%, and the passband ripple was
      only 0.06 dB.

PMID- 18087389
TI  - Low-power high-efficiency wavelength conversion based on modulational instability
      in high-nonlinearity fiber.
AB  - Bandwidth and peak efficiency are enhanced for wavelength conversion based on
      induced modulation instability by use of dispersion-shifted fiber in which the
      nonlinearity (n(2)/A(eff)) is enhanced by a factor of ~4.5 over that of
      conventional dispersion-shifted fiber. We experimentally obtain a peak conversion
      efficiency as high as 28 dB over a 40-nm bandwidth with 600 mW of peak pump
      power. Considerations for further enhancement of fiber-based wavelength
      conversion are also discussed.

PMID- 18087390
TI  - Spectral characterization of fiber gratings with high resolution.
AB  - We demonstrate a high-resolution technique to measure the optical magnitude and
      phase responses of fiber gratings. The technique employs single-sideband
      modulation of an optical source and has spectral resolution in the hertz regime.
      The technique is demonstrated by measurement of the phase ripples of unapodized
      and apodized chirped gratings as well as the transmission spectrum of a pi-phase
      shifted grating. Although it is demonstrated on fiber gratings, the technique is
      applicable to any optical device.

PMID- 18087391
TI  - Diode-bar end-pumped high-power Nd:Y(3)Al(5)O(12) planar waveguide laser.
AB  - A compact high-power planar waveguide laser end pumped by a diode-bar is
      reported. The waveguide was fabricated by liquid-phase epitaxy and had an 80
      microm-thick, 1.5-at. % Nd:Y(3)Al(5)O(12) core on a Y(3)Al(5)O(12) substrate. A
      maximum output power of 6.2 W was obtained at 1.064 microm when the device was
      pumped with a 20-W diode bar operating near 807 nm, giving an overall optical-to
      optical conversion efficiency of 31%. The total device length was 5 cm.

PMID- 18087392
TI  - Ultrahigh 47-dB optical drop rejection multiwavelength add--drop filter using
      spatial filtering and dual bulk acousto-optic tunable filters.
AB  - A new high-speed, ultrahigh cross-talk-suppression multiwavelength add-drop
      optical filter structure is demonstrated with two bulk acousto-optic tunable
      filters. With simple spatial blocks, an average -47-dB optical suppression is
      measured for the unwanted wavelengths at the filter output ports. The filter is
      tested for the three standard visible wavelengths, red, green, and blue, and
      demonstrates a switching time of 0.65micros and an average optical loss of 5 dB.
      Applications for this filter include multiwavelength switching applications such
      as wavelength-division-multiplexed optical communications.

PMID- 18087393
TI  - Polarization decay in ultrafast collinear nondegenerate four-wave mixing in a
      semiconductor amplifier.
AB  - The time evolution of the nondegenerate four-wave mixing polarization in a
      semiconductor optical amplifier (SOA) is investigated theoretically by solution
      of the semiconductor Bloch equations, including all the relevant scattering
      processes. The results are in direct agreement with recent experimental
      measurements, showing that a treatment of coherent and incoherent effects in
      SOA's on the level of a microscopic theory is highly desirable.

PMID- 18087394
TI  - Spatial photoselection of single molecules on the surface of spherical
      microcavities.
AB  - We show that ultrasensitive microdroplet-stream fluorescence techniques combined
      with surfactant forms of Rhodamine dyes can be used to probe single molecules on
      the surfaces of spherical microcavities. Individual octadecyl Rhodamine B
      molecules, shown previously by ensemble measurements to be localized and oriented
      at the surfaces of liquid microspheres, were spatially photoselected primarily
      along great circles lying perpendicular or parallel to the detection axis by use
      of polarized laser excitation. A polarization dependence is observed in the
      distribution of single-molecule fluorescence amplitudes that can be interpreted
      qualitatively in terms of position-dependent fluorescence-collection
      efficiencies.

PMID- 18087395
TI  - Fixed-frequency cavity ringdown diagnostic for atmospheric particulate matter.
AB  - A nonresonant cavity ringdown diagnostic to measure light attenuation from
      atmospheric particulate matter at 532- and 355-nm wavelengths is described. The
      presence of atmospheric particulate is clearly detectable with this technique, as
      demonstrated by experimental results. The extinction cross section is higher at
      355 than at 532 nm, although we were able to purchase significantly higher
      reflectivity optics at 532 nm. The expected advantage at 355 nm is thus lost.
      This new technique is compared with a commercially available instrument, and
      sensitivity limitations are discussed.

PMID- 18087396
TI  - Doppler-free two-photon spectrum of SF(6) for metrological purposes.
AB  - We report on our systematic investigation of strong Doppler-free two-photon
      absorption in the middle infrared. The absorption frequencies for two
      counterpropagating waves of identical frequencies are predicted. Five of these
      transitions were observed with sub-Doppler resolution with a sideband CO(2) laser
      and were measured with 10-kHz accuracy. Knowledge of these strong two-photon
      absorptions frequencies will allow the improvement of secondary frequency
      standards in the infrared.

PMID- 18087397
TI  - Lifetimes of thermally fixed holograms in LiNbO(3):Fe crystals.
AB  - The thermal erasure decay at different temperatures of holographic gratings
      thermally fixed in iron-doped lithium niobate has been exhaustively studied. An
      activation energy of 0.94 eV was found to be independent of the grating fringe
      spacing. At a given temperature the decay time is strongly dependent on the
      grating spacing. This dependence is well fitted to a square fringe spacing law,
      as predicted theoretically. From the experimental data the room-temperature
      hologram lifetime under illumination is extrapolated, giving as a result
      t(years)=(5.2+/-0.2)?(2) , with the grating spacing ? in micrometers.

PMID- 18087398
TI  - Cross talk of wavelength-multiplexed quasi-infinite holograms.
AB  - The cross talk of wavelength-multiplexed quasi-infinite (written in polychromatic
      light) holograms is evaluated. Under plausible conditions this cross talk is
      negligible. The typical information capacity limit of such holograms is evaluated
      as 10(12) bits for a 1-cm(3) volume.

PMID- 18087399
TI  - Simultaneous measurement of the phase and group indices and the thickness of
      transparent plates by low-coherence interferometry.
AB  - We propose and demonstrate a novel technique for simultaneous measurement of the
      phase index, n(p) , the group index, n(g) , and the thickness, t , of transparent
      plates by use of a low-coherence interferometer. The output light from a
      superluminescent diode is focused upon the front plane of a transparent plate
      that is used as the sample. The sample stage is subsequently moved until the
      light is focused upon the rear plane of the plate. Measurement of the stage
      movement distance and the corresponding optical path difference allows us to
      determine both n(p) and n(g) . By placing the sample between two glass plates, we
      measured n(p) , n(g) , and t simultaneously, with an error of 0.3% or less, for
      nearly 1-mm-thick transparent plates, including glass and electro-optic crystals.

PMID- 18087400
TI  - Characteristics of a 128 x 128 liquid-crystal spatial light modulator for wave
      front generation.
AB  - Spatial and temporal characteristics of a 128x128 zero-twist nematic liquid
      crystal spatial light modulator are investigated for wave-front generation at a
      wavelength of 632.8 nm. The modulator is found to have the capability of
      producing at least eight phase levels between 0 and 2pi , and the rate of
      arbitrary phase modulation is limited to approximately 4.5 Hz. Wave-front
      generation of the first 55 Zernike polynomials is demonstrated.

PMID- 18087401
TI  - Miniature liquid-crystal-on-silicon display assembly.
AB  - A novel integrated assembly process for miniature liquid-crystal-on-silicon
      displays using photodefinable benzocyclobutene resin is presented. Spin coating
      speed defines the cell gap, photolithography defines the cell perimeter and
      spacers, and thermocompression bonding provides the adhesion. The photodefined
      adhesive spacers provide thin liquid-crystal cell gap control (<2.5 microm) with
      excellent uniformity (+/-100 nm) for glass-on-glass and glass-on-silicon
      assemblies. The resin is compatible with common liquid-crystal alignment films
      and exhibits a bonding shear strength of 22+/-3.2 MPa The assembly process flow
      and characterization of demonstration devices are described.

PMID- 18087402
TI  - Frequency-swept ultrasound-modulated optical tomography of scattering media.
AB  - A novel frequency-swept ultrasound-modulated optical tomography technique was
      developed to image scattering media. A frequency-swept ultrasonic wave was used
      to modulate the laser light passing through a scattering medium. The modulated
      light was received by an optical detector and was heterodyned with a reference
      frequency sweep. The heterodyned signal was recorded in the time domain and was
      then analyzed in the frequency domain to yield a one-dimensional image along the
      ultrasonic axis. Multiple one-dimensional images obtained at various positions
      perpendicular to the ultrasonic axis were combined to yield a two-dimensional
      tomographic image of the medium.

PMID- 18087403
TI  - Time-resolved optical backscattering model in highly scattering media.
AB  - A time-resolved backscattering model, which combines a single large-angle
      scattering with multiple small-angle scatterings, is used to produce a scattered
      light profile about a medium. Inhomogeneity of the medium is included in the
      model. Some multidimensional integrals can be evaluated analytically.

PMID- 18087404
TI  - Fiber coupling efficiency for random light and its applications to lidar.
AB  - Employing the van Cittert-Zernike theorem of classical coherence theory, we
      derive a general expression for the efficiency with which quasi-monochromatic
      random light can be coupled to an optical fiber by means of a lens. For the
      important case of a source with Gaussian intensity distribution, we obtain and
      discuss the dependence of the coupling efficiency to single-mode fibers on the
      lens-to-fiber coupling geometry as well as on the ratio of lens size to speckle
      size. A specialization to the emerging fields of both incoherent and coherent
      fiber-based lidar applications shows that a maximum coupling efficiency of
      approximately 42% can be obtained for a monostatic system.

PMID- 18087405
TI  - Intensity-based modal analysis of partially coherent beams with Hermite-Gaussian
      modes.
AB  - Many partially coherent beams are made up of a superposition of mutually
      uncorrelated Hermite-Gaussian modes. We prove that knowledge of the transverse
      intensity profile of such a beam is sufficient for evaluating the weights of the
      modes in an exact way. Simulations indicate that the proposed method resists
      noise well.

PMID- 18087406
TI  - Liquid-crystal adaptive lenses with modal control.
AB  - We report on a novel approach to the realization of nematic liquid-crystal (LC)
      phase correctors to form spherical and cylindrical wave fronts. A LC cell with a
      distributed reactive electrical impedance was driven by an ac voltage applied to
      the cell boundary to yield the desired spatial distribution of the refractive
      index. The two-dimensional function of the phase delay introduced into the light
      beam depends on the frequency of the ac control voltage, the geometry of the
      boundary electrode surrounding the LC cell, and the electrical parameters of the
      cell. We realized a cylindrical adaptive lens with a clear aperture of 15 mm x
      4mm and a spherical adaptive lens with circular aperture of 6.5 mm. Both devices
      are capable of focusing collimated light in the range infinity...0.5 m.

PMID- 18087407
TI  - Dynamic range expansion of a Shack-Hartmann sensor by use of a modified
      unwrapping algorithm.
AB  - An algorithm for expanding the dynamic range of Shack--Hartmann sensors is
      proposed. The distribution of the spot dislocations is treated with a modified
      unwrapping algorithm that is widely used in interferometry. The algorithm unwraps
      the spot dislocations and assigns the spots to their original subapertures,
      leading to a huge expansion of the dynamic range. For the proposed algorithm
      there remains a limitation on the maximum wave-front curvature instead of on the
      maximum wave-front slope. Examples are given that show spot fields that were
      wrapped four times; the measured wave front had a peak-to-valley value of 116
      lambda .

PMID- 18087408
TI  - Beam-propagation method for analysis of z -dependent structures that uses a local
      oblique coordinate system.
AB  - In the most current beam-propagation method (BPM), the coupling between the
      transverse and the longitudinal fields in z -dependent structures is ignored
      under the staircase approximation, which results in violation of power
      conservation. We propose a novel BPM that is derived in a local oblique
      coordinate system to analyze z -dependent structures accurately and efficiently
      without taking the staircase approximation. The coupling between the transverse
      and the longitudinal fields is automatically included in the local oblique
      coordinate system, and power is thus conserved if the reflection is neglected.

PMID- 18087409
TI  - High-intensity nanosecond photorefractive spatial solitons.
AB  - We report the observation of high-intensity solitons in a bulk strontium barium
      niobate crystal. The solitons are observed by use of 8-ns optical pulses with
      optical intensities greater than 100 MW/cm(2). Each soliton forms and attains its
      minimum width after roughly ten pulses and reaches e(-1) of the steady-state
      width after the first pulse. We find good agreement between experimental
      observations and theoretical predictions for the soliton existence curve.

PMID- 18087410
TI  - 1.5-microm-band wavelength conversion based on difference-frequency generation in
      LiNbO3 waveguides with integrated coupling structures.
AB  - We report wavelength conversion within the 1.5-mum telecommunications band based
      on difference-frequency generation in periodically poled lithium niobate
      waveguides with integrated coupling structures. A conversion efficiency of -7 dB
      and a normalized efficiency of 260%/W are demonstrated. Static tests show that
      the conversion bandwidth is 72 nm and the conversion efficiency is constant over
      the 20-dB range of input powers tested.

PMID- 18087411
TI  - High-speed properties of a phase-modulation scheme based on electromagnetically
      induced transparency.
AB  - Recently a cross-phase modulation scheme that yields giant Kerr nonlinearities by
      use of an electromagnetically induced transparency (EIT) was proposed [Schmidt
      and Imamoglu, Opt. Lett. 21, 1936 (1996)]. We analyze the high-speed properties
      of this scheme for short-pulse propagation. We discuss the relevant losses in
      this system and show that for short pulses one-photon losses are dominant. We
      demonstrate that over the entire bandwidth the attainable phase shift in an EIT
      scheme with a quasi-cw coupling field is orders of magnitude higher than in a
      conventional three-level scheme or in EIT schemes, in which matched pulses are
      used to create the transparency.

PMID- 18087412
TI  - 16-microm infrared generation by difference-frequency mixing in diffusion-bonded
      stacked GaAs.
AB  - Tunable 90-ps 15.6-17.6-microm coherent radiation was generated by means of
      difference-frequency mixing in diffusion-bonded-stacked GaAs. The sample
      consisted of 24 alternately rotated layers with a total length of 6 mm and with
      low optical loss to achieve third-order quasi-phase matching. The wavelength
      tuning curve was close to the theoretical prediction, demonstrating that the
      bonding process maintained nonlinear optical phase matching over the entire
      interaction length. Maximum conversion efficiency of 0.7%, or 5% internal quantum
      efficiency, was measured at 16.6 microm, consistent with the theoretical
      predictions.

PMID- 18087413
TI  - Dispersion-managed solitons with net positive dispersion.
AB  - Propagation of dispersion-managed solitons in the net positive-dispersion regime
      is studied. A new form of sideband generation that is due to perturbations is
      identified. Some collision anomalies are pointed out.

PMID- 18087414
TI  - Alleviation of thermally induced phase mismatch in CsLiB6O10 crystal by means of
      temperature-profile compensation.
AB  - A new mechanism was found to alleviate the thermally induced phase mismatch of
      nonlinear optical crystals. By cooling CsLiB>(6)O(10) at an elevated crystal
      temperature with gas, we improved laser conversion efficiency from green (532 nm)
      to UV (266 nm) 2.3 times compared with that without cooling. In situ observation
      of the temperature profile on the output surface revealed that such cooling
      initiates a negative temperature profile that compensates for the positive
      profile generated from laser absorption. A 10.6-W UV output with excellent
      stability was generated. The optimum crystal length was substantially extended.

PMID- 18087415
TI  - Soliton interaction in strongly dispersion-managed optical fibers.
AB  - We derive an expression for the speed with which neighboring solitons attract or
      repel each other in dispersion-managed fiber systems. We show that the collapse
      distance can be increased by an order of magnitude by use of quasi-solitons.

PMID- 18087416
TI  - Noise-induced amplitude and chirp jitter in dispersion-managed soliton
      communications.
AB  - An analytic theory is presented that demonstrates that noise-induced amplitude
      and quadratic chirp jitter in a dispersion-managed soliton system can impose a
      fundamental transmission limit. Using a variational method, we show that the
      nonlinear amplitude and chirp dynamics are well approximated by a two-dimensional
      random-walk process.

PMID- 18087417
TI  - Gradient-index planar optics for optical interconnections.
AB  - Use of a gradient-index (GRIN) substrate is proposed as a novel signal
      propagation medium for planar optics. The GRIN substrate provides planar optics
      designers not only a three-dimensional light propagation space but also smart
      optical diffraction-limited imaging. Experimental results on the imaging of an
      input signal to multiple destinations by the GRIN planar optics are presented.

PMID- 18087418
TI  - Excited-state absorption in the range of pumping and laser efficiency of
      Cr4+:forsterite.
AB  - The absorption saturation and the laser efficiency of Cr(4+): forsterite were
      measured with 1064-nm (E || b), 980-nm (E || c), and 780-nm (E || b) pulsed laser
      pumping. A slope efficiency of 32% was obtained for the 980-nm (E || c) pump
      wavelength, where the excited-state absorption losses were shown to be
      negligible.

PMID- 18087419
TI  - Ultrahigh long-term dimensional stability of a sapphire cryogenic optical
      resonator.
AB  - We report on the ultrahigh long-term dimensional stability of a crystalline
      cryogenic optical resonator (CORE) cooled to liquid-helium temperature. The
      frequency of a Nd:YAG laser stabilized to a CORE was compared over long times
      with an independent laser system, a frequency-doubled Nd:YAG laser stabilized to
      a hyperfine line of molecular iodine at 532 nm. Over a 6-month period the drift
      was less than 3 kHz. The dimensional stability of the CORE is thus more than 2
      orders of magnitude higher than that of the best ultralow-expansion glass ceramic
      cavities at room temperature.

PMID- 18087420
TI  - Efficient self-seeding of a pulsed Ti3+:Al2O3 laser.
AB  - We describe the design considerations and operating characteristics of a compact,
      widely tunable, narrow-linewidth, megawatt-class pulsed laser system based on
      Ti(3+):Al(2)O(3) (Ti:sapphire) pumped by the second harmonic of a 1.06-microm
      Nd:YAG laser. The system delivers 10 mJ in a 5-ns near-transform-limited single
      longitudinal-mode (SLM) pulse with a threshold of 20 mJ and a slope efficiency
      greater than 40%. By the technique of self-seeding, in which a portion of the
      gain medium's spontaneous fluorescence is coupled back to the laser cavity, SLM
      operation may be obtained across the entire gain profile of Ti:sapphire with a
      minimum number of optical components and without external seeding.

PMID- 18087421
TI  - High-power superfluorescent source with a side-pumped Yb-doped double-cladding
      fiber.
AB  - A compact superfluorescent source based on an Yb-doped double-cladding fiber
      amplifier is described. The packaged amplifier is pumped at 975 nm by side
      coupling emission from a 2.0-W broad-stripe laser diode through an imbedded V
      groove. The fiber source generates 485 mW of broadband emission centered at 1055
      nm with a 41-nm FWHM flat power spectrum.

PMID- 18087422
TI  - Generation of the fourth harmonic of a femtosecond Ti:sapphire laser.
AB  - A high-repetition-rate femtosecond laser system operating, for the first time to
      our knowledge, in the spectral region near 200 nm is described. Frequency
      quadrupling of a mode-locked Ti:sapphire laser results in maximum average powers
      of 6 mW (165-fs pulses) and 15 mW (340-fs pulses) at 82 MHz. The shortest
      wavelength achieved is 193.7 nm.

PMID- 18087423
TI  - Wave-front correction of femtosecond terawatt lasers by deformable mirrors.
AB  - Wave-front correction and focal spot improvement of femtosecond laser beams have
      been achieved, for the first time to our knowledge, with a deformable mirror with
      an on-line single-shot three-wave lateral shearing interferometer diagnostic.
      Wave-front distortions of a 100-fs laser that are due to third-order nonlinear
      effects have been compensated for. This technique, which permits correction in a
      straightforward process that requires no feedback loop, is also used on a 10-TW
      Ti:sapphire-Nd:phosphate glass laser in the subpicosecond regime. We also
      demonstrate that having a focal spot close to the diffraction limit does not
      constitute a good criterion for the quality of the laser in terms of peak
      intensity.

PMID- 18087424
TI  - Collinear type II second-harmonic-generation frequency-resolved optical gating
      for use with high-numerical-aperture objectives.
AB  - Ultrashort-pulse lasers are now commonly used for multiphoton microscopy, and
      optimizing the performance of such systems requires careful characterization of
      the pulses at the tight focus of the microscope objective. We solve this problem
      by use of a collinear geometry in frequency-resolved optical gating that uses
      type II second-harmonic generation and that allows the full N.A. of the
      microscope objective to be used. We then demonstrate the technique by measuring
      the intensity and the phase of a 22-fs pulse focused by a 20x, 0.4-N.A. air
      objective.

PMID- 18087425
TI  - Simultaneous Cartesian coordinate display of defocused optical transfer
      functions.
AB  - We show that by using a binary spatial filter and a square-law detector we can
      display all the defocused optical transfer functions (OTF's) in a given study in
      a single picture. The resulting unique picture has as its horizontal coordinates
      the spatial frequency and as its vertical coordinates the amount of defocus. The
      gray-level variations are proportional to the modulus of the OTF, that is, the
      modulation transfer function. Numerical simulations are included.

PMID- 18087426
TI  - Spectroscopic detection of methane by use of guided-wave diode-pumped difference
      frequency generation.
AB  - We report spectroscopic gas detection by the use of mid-infrared difference
      frequency mixing of two diode lasers in a channel waveguide. The waveguide was
      fabricated by annealed proton exchange in periodically poled lithium niobate. We
      generated 3.43-3.73-microm tunable radiation in a single waveguide at room
      temperature by mixing diode lasers near 780 and 1010 nm. High-resolution spectra
      of methane were obtained in 2 s with electronically controlled frequency scans of
      45 GHz. The use of highly efficient waveguide frequency converters pumped by
      fiber-coupled diode lasers will permit construction of compact, solid-state, room
      temperature mid-infrared sources for use in trace-gas detection.

PMID- 18087427
TI  - One-step two-dimensional rainbow-holographic technique with a nonlaser light
      source.
AB  - A technique for recording two-dimensional rainbow holograms by use of a nonlaser
      light source is described. Multicolor holograms are recorded in one step. The
      optical setup is lensless. The recording light source is an InGa lamp that
      provides a spectrum from UV to blue. The slit effect is generated by replication
      from the slit master plates.

PMID- 18087429
TI  - Cross-polarized backscatter in optical coherence tomography of biological tissue.
AB  - We have observed that cross-polarized backscatter measured by optical coherence
      tomography of human skin in vivo is surprisingly strong. We identify and give
      evidence of its main origins: single scattering from nonspherical particles and
      multiple scattering by particles with sizes much larger than a wavelength. Our
      findings show that depolarized light scattered by dense large-diameter particles
      maintains a high degree of temporal coherence and that differential-polarization
      imaging improves contrast between particles of different sizes.

PMID- 18087428
TI  - Velocity-estimation accuracy and frame-rate limitations in color Doppler optical
      coherence tomography.
AB  - Color Doppler optical coherence tomography (CDOCT) is a recent innovation that
      allows spatially localized flow-velocity mapping simultaneously with
      microstructural imaging. We present a theoretical model for velocity-image
      formation in CDOCT. The proportionality between the heterodyne detector current
      Doppler power spectrum in CDOCT and the optical source power spectrum is
      established. We show that stochastic modifications of the Doppler spectrum by
      fluctuating scatterer distributions in the flow field give rise to unavoidable
      velocity-estimation inaccuracies as well as to a fundamental trade-off between
      image-acquisition rate and velocity precision. Novel algorithms that permit high
      fidelity depth-resolved measurements of velocities in turbid media are also
      reported.

PMID- 18087431
TI  - Speckle statistics in partially corrected wave fronts.
AB  - Wave fronts distorted by the atmosphere preserve high-spatial-frequency
      information. This information can be retrieved by use of adaptive optics systems
      to correct the incoming wave front. This correction should be as nearly complete
      as possible. In experiments performed in the visible, only partial compensation
      is attainable. We provide a theoretical model to predict the intensity statistics
      of the light in the image center as a function of the number of Zernike
      polynomials corrected.

PMID- 18087430
TI  - Space bandwidth-efficient realizations of linear systems.
AB  - One can obtain either exact realizations or useful approximations of linear
      systems or matrix-vector products that arise in many different applications by
      implementing them in the form of multistage or multichannel fractional Fourier
      domain filters, resulting in space-bandwidth-efficient systems with acceptable
      decreases in accuracy. Varying the number and the configuration of filters
      enables one to trade off between accuracy and efficiency in a flexible manner.
      The proposed scheme constitutes a systematic way of exploiting the regularity or
      structure of a given linear system or matrix, even when that structure is not
      readily apparent.

PMID- 18087432
TI  - Mueller matrix for characterization of one-dimensional rough perfectly reflecting
      surfaces in a conical configuration.
AB  - Theoretical results of the use of a Mueller matrix to characterize a one
      dimensional rough perfectly reflecting, single-scattering surface in a conical
      configuration are presented. The conical Mueller matrix (CMM) is derived from the
      known Mueller matrix of this kind of surface in the plane of incidence [the plane
      Mueller matrix (PMM)]. The key argument is that, as the PMM is considered to be a
      Mueller-Jones matrix, an appropriate rotation of the complex amplitude matrix
      provides the conic Mueller matrix.

PMID- 18087433
TI  - Phase-shifted laser feedback interferometry.
AB  - We have introduced the techniques of phase-shifting interferometry into a laser
      feedback interference microscope based on a helium-neon laser. With moderate
      feedback, multiple reflections between the sample and the laser are shown to be
      negligible, and the interferometer responds sinusoidally with a well
      characterized fringe modulation. One can obtain higher signal-to-noise ratios by
      determining the number of additional terms required for modeling the effect of
      multiple reflections on the phase and visibility measurements in the high
      feedback regime. Changes in optical path length are determined with nanometer
      precision without phase averaging or lock-in detection.

PMID- 18087434
TI  - Blazed binary subwavelength gratings with efficiencies larger than those of
      conventional echelette gratings.
AB  - We introduce a new structural cutoff beyond which subwavelength gratings cease to
      behave as homogeneous media and discuss its effects on the proper selection of
      the sampling periods of subwavelength diffractive elements. According to this
      analysis, a 3lambda-period blazed binary grating composed of square pillars is
      designed for He-Ne operation and is fabricated by etching of a TiO>(2) layer
      deposited upon a glass substrate. Its first-order measured diffraction efficiency
      is 12% larger than the theoretical efficiency of an ideal blazed echelette
      grating in glass with the same period.

PMID- 18087435
TI  - Display of spatial coherence.
AB  - The mutual-intensity function plays a major role in characterizing quasi
      monochromatic, partially coherent optical signals. We demonstrate an optical
      system for displaying the mutual intensity of a one-dimensional input beam. The
      experimental system is based on the fact that the mutual intensity of a signal
      can be expressed as the ensemble averaging of a cross-correlation operation
      between two related optical signals. The setup consists of a Sagnac
      interferometer followed by an optoelectronic joint transform correlator.
      Experimental results demonstrate the capabilities of the mutual-intensity
      analyzer.

PMID- 18087436
TI  - Earth-to-deep-space optical communications system with adaptive tilt and
      scintillation correction by use of near-Earth relay mirrors.
AB  - Performance of an Earth-to-deep-space optical telecommunications system is
      degraded by distortion of the beam as it propagates through the turbulent
      atmosphere. Conventional approaches to correcting distortions, based on natural
      or artificial guide stars, have practical difficulties or are not adequate for
      correction of distortions, which are important for Earth-to-deep-space optical
      links. A beam-relay approach that overcomes these difficulties is discussed. A
      downward-directed laser near an orbiting relay mirror provides a reference for
      atmospheric correction. Adaptive optics at the ground station compensate the
      uplink beam so that after it passes through the atmosphere uplink propagation
      effects are removed. The orbiting mirror then directs the corrected beam to the
      distant spacecraft.

PMID- 18087437
TI  - Spatiotemporal collapse in a nonlinear waveguide with a randomly fluctuating
      refractive index.
AB  - Analytical results, based on the virial theorem and the Furutsu-Novikov theorem,
      of the spatiotemporal evolution of a pulse in a nonlinear waveguide with a
      randomly fluctuating refractive index are presented. For initial conditions in
      which total collapse occurs in a homogeneous waveguide, random fluctuations
      postpone the collapse. Sufficiently large-amplitude and short-wavelength
      fluctuations can cause an initially localized pulse to spread instead of
      contracting. We show that the disorder can be applied to induce a high degree of
      controllability of the spatiotemporal extent of the pulses in the nonlinear
      waveguide.

PMID- 18087438
TI  - Self-pumped phase-conjugate diode-pumped Nd:YAG loop resonator.
AB  - We demonstrate a self-pumped phase-conjugate diode-pumped Nd:YAG loop resonator.
      In the injected configuration a maximum phase-conjugate reflectivity of 32 is
      obtained. The output beam has a pulse shape of ~30 ns , which shows the self- Q 
      switching ability of the resonator. By use of a low-refractive-output coupler, a
      self-starting version was produced. The resonator operated in a stable
      diffraction-limited TEM(00) mode, even with severe intracavity phase aberrations.
      A maximum energy of 5.5 mJ (2.4% of the energy of the high-brightness stacks that
      was incident upon the Nd:YAG crystals) in a 20-ns single-longitudinal-mode pulse
      was measured.

PMID- 18087439
TI  - Efficient difference-frequency generation of 7- 20-mum radiation in CdGeAs(2).
AB  - Continuously tunable 6.8-20.1-mum mid-infrared radiation has been achieved by the
      use of frequency generation in CdGeAs(2). The signal and the idler output of an
      Er-laser-pumped ZnGeP(2) optical parametric generator was used as the pump. The
      maximum external conversion efficiency reached 20%.

PMID- 18087440
TI  - Multifunction optical filter with a Michelson-Gires-Tournois interferometer for
      wavelength-division-multiplexed network system applications.
AB  - We propose using a novel multifunction optical filter with a Michelson-Gires
      Tournois interferometer (MGTI) for future smart wavelength-division-multiplexed
      network system applications. The MGTI filter is a typical Michelson
      interferometer in which one of its reflecting mirrors is replaced with a Gires
      Tournois resonator. One unique feature of this device is that it can function as
      a channel-passing (CP), a channel-dropping (CD), or a wide-bandpass (BP) filter,
      depending on the interferometer arm-length difference. Other interesting features
      are that (1) the linewidths of both the CP and the CD filter are twice as narrow
      as that of a typical Fabry-Perot filter with similar parameters, (2) theoretical
      visibility is always unity regardless of the mirror reflectance value, and (3)
      the BP filter has an excellent boxlike response function. Numerical results
      showing these characteristics are presented.

PMID- 18087441
TI  - Measurement of a parameter limiting the analysis of the first-order polarization
      mode dispersion ef fect.
AB  - A necessary condition to guarantee the existence of the principal state of
      polarization is experimentally examined. The P parameter, which is defined as the
      product of the differential group delay and the bandwidth of the principal state
      of polarization, is measured. The P parameter of long single-mode fibers is
      assessed. Average P values of 0.26 for dispersion-shifted fiber and 0.45 for
      conventional single-mode fiber were obtained. Combining these results with
      published results, one finds that P is not determined solely from the state of
      the polarization-mode coupling.

PMID- 18087442
TI  - Spiral morphology-dependent resonances in an optical fiber: effects of fiber tilt
      and focused Gaussian beam illumination.
AB  - Spiral morphology-dependent resonances have been observed in a tilted optical
      fiber. The polarization-preserving and the cross-polarized elastic-scattering
      spectra for plane-wave illumination show that the wavelengths of the resonances
      are blueshifted quadratically as the fiber tilt angle increases. When a focused
      Gaussian beam illuminates the fiber at its edge, the resonances are blueshifted
      and broadened as the detector is offset from the scattering plane with the
      maximum scattering intensity. The blueshift with focused beam illumination is
      also a consequence of the spiral resonances.

PMID- 18087443
TI  - One-color one-beam pumping of Er(3+)-doped ZBLAN glasses for a three-dimensional
      two-step excitation display.
AB  - We demonstrate a one-color one-beam pumping method for a three-dimensional two
      step excitation fluorescent display with Er(3+) -doped ZBLAN glass. A localized
      green fluorescent spot is obtained by use of a focused pump-light beam at 979 nm.
      The quantum efficiency of the two-step excitation fluorescence is investigated in
      a time-dependent analysis and an experiment with a pulsed pump light.

PMID- 18087444
TI  - Near-field scanning optical microscopy of single molecules by femtosecond two
      photon excitation.
AB  - We present a demonstration of near-field scanning optical microscopy of single
      molecules based on ultrafast two-photon-induced fluorescence. Measurements were
      performed by use of 100-fs pulses at 800 nm from a Ti:sapphire laser to excite
      the two-photon transition in Rhodamine B molecules. Although near-field probes
      are normally metal coated to achieve superresolution, we used uncoated tips to
      achieve sufficiently high optical powers to generate acceptable fluorescence
      emission rates. Images of single molecules demonstrate a resolution of ~175nm(<
      lambda/4) on a topographically smooth surface, which surpasses the apparent
      lambda/2 resolution limit for uncoated tips operating in the linear response
      regime.

PMID- 18087445
TI  - Single-shot spatiotemporal terahertz field imaging.
AB  - Using an optically chirped pulse in an electro-optic detection system, we image
      the spatiotemporal distribution of a terahertz (THz) pulse. We demonstrate single
      shot THz field imaging of photoconductive emitters.

PMID- 18087446
TI  - Efficient generation of narrow-bandwidth picosecond pulses by frequency doubling
      of femtosecond chirped pulses.
AB  - We demonstrate efficient generation of picosecond narrow-bandwidth pulses by
      frequency mixing of broadband opposite chirped pulses in a type I doubling
      crystal. This procedure allows us to produce picosecond pulses that are perfectly
      synchronized with femtosecond pulses. The experiment shows a decrease of the
      initial bandwidth by a factor of more than 30, while a high conversion efficiency
      is maintained.

PMID- 18087447
TI  - Ultrafast time-resolved quantum beats in the polarization state of coherent
      emission from quantum wells.
AB  - Dual-channel spectral interferometry is used to measure the ellipticity, the
      orientation of the polarization ellipse, and the sense of rotation of the four
      wave-mixing signal from a GaAs-AlGaAs multiple quantum well. Each parameter is
      observed to oscillate dramatically at the heavy-hole-light-hole quantum beat
      frequency. During each beat period (in the strong quantum beat regime), the
      ellipticity oscillates twice between linear and almost-circular polarization, the
      orientation of the polarization ellipse rotates through a complete 180 degrees ,
      and the sense of rotation changes from left- to right-circular polarization.

PMID- 18087448
TI  - Image reconstruction from pairs of Fourier-transform magnitude.
AB  - The retrieval of phase information from only the magnitude of the Fourier
      transform of a signal remains an important problem for many applications. We
      present an algorithm for phase retrieval when there exist two related sets of
      Fourier-transform magnitude data. The data are assumed to come from a single
      object observed in two different polarizations through a distorting medium, so
      the phase component of the Fourier transform of the object is corrupted. Phase
      retrieval is accomplished by minimization of a suitable criterion function, which
      can take three different forms.

PMID- 18087449
TI  - Optical implementations of the Radon-Wigner display for one-dimensional signals.
AB  - New optical implementations of the Radon-Wigner display for a one-dimensional
      signal are proposed based on the fractional Fourier transform. The setups involve
      only one varifocal lens. Furthermore, the same magnification can be realized
      simultaneously for all the fractional transform orders, which is quite convenient
      for practical applications.

PMID- 18087450
TI  - Input-image homogenization as a method to improve a correlator's discrimination
      capability.
AB  - We propose an input-image preprocessing method consisting of homogenization of
      the image to improve the discrimination capability of a correlation-based
      recognition process. This method is an approximation of the optimal filter. It
      offers the advantage that correlation with the preprocessed images can easily be
      implemented in an optical correlator working with phase-only spatial light
      modulators.

PMID- 18087451
TI  - Squeezing in downconversion in a quasi-phase-matched medium.
AB  - We consider the generation of squeezed light in the process of degenerate
      downconversion in a quasi-phase-matched periodically poled nonlinear medium. The
      squeezing in the downconverted mode is analyzed for different orders of quasi
      phase matching and for phase-mismatch parameter as well as varying pump input
      powers. The results show that a high degree of squeezing and high powers can be
      obtained for well-matched interactions.

PMID- 18087452
TI  - External-cavity broad-area laser diode operating on the D(1) line of cesium.
AB  - We present an external-cavity laser diode characterized by an intracavity
      cylinder lens to compensate for the astigmatism of the laser. This setup was
      applied to a broad-area laser diode operating on the D(1) line of the cesium atom
      at 894 nm, yielding single-mode emission. A saturated-absorption experiment on
      that atomic line tested the laser performance.

PMID- 18087453
TI  - LiNbO(3) platforms for optical fiber alignment.
AB  - A technique for incorporating a groove into a LiNbO(3) substrate is described.
      Both V grooves for fiber alignment and vertical grooves for waveguide end-face
      formation can be fabricated with this technique. The proposed fabrication method
      is based on an excimer-laser ablation and a high-speed rotation saw cut for
      LiNbO(3) . The former process provides a variety of cross-sectional groove shapes
      by changing the ablation mask shape of LiNbO(3) , and the latter provides an
      optical-quality cutting face. The proposed fabrication method is simple and
      provides low-cost optical platforms not only for LiNbO(3) but also for glasses,
      polymers, and semiconductors.

PMID- 18087454
TI  - Gouy shift and temporal reshaping of focused single-cycle electromagnetic pulses:
      errata.

PMID- 18087455
TI  - Do evanescent waves contribute to the far field? Errata.

PMID- 18087456
TI  - Increasing the angular tolerance of resonant grating filters with doubly periodic
      structures.
AB  - One can increase the angular tolerance of resonant grating filters without
      modifying the spectral bandwidth by adding a second grating component parallel to
      the first one. The angular tolerance and the filter linewidth can be controlled
      by the designer in an independent way. Numerical results show that this property
      permits the use of waveguide-grating filters with standard collimated beams.

PMID- 18087457
TI  - Spectrally encoded confocal microscopy.
AB  - An endoscope-compatible, submicrometer-resolution scanning confocal microscopy
      imaging system is presented. This approach, spectrally encoded confocal
      microscopy (SECM), uses a quasi-monochromatic light source and a transmission
      diffraction grating to detect the reflectivity simultaneously at multiple points
      along a transverse line within the sample. Since this method does not require
      fast spatial scanning within the probe, the equipment can be miniaturized and
      incorporated into a catheter or endoscope. Confocal images of an electron
      microscope grid were acquired with SECM to demonstrate the feasibility of this
      technique.

PMID- 18087458
TI  - Three-dimensional modeling of amplitude-object imaging in scanning near-field
      optical microscopy.
AB  - The imaging properties of the transmission-illumination mode of a scanning near
      field optical microscope are investigated. Three-dimensional calculations of the
      power transmitted into classically allowed and forbidden regions for a
      nonsymmetrically positioned amplitude object are implemented by use of the finite
      difference time-domain solution of Maxwell's equations. The evolution of the
      images with the distance from the object as well as the effect of the
      polarization of the illumination is shown. The computations show that for
      applications involving the imaging of an amplitude object, the use of the allowed
      light is preferred. Collection of light from both the allowed and the forbidden
      zones leads to degraded contrast and resolution.

PMID- 18087459
TI  - Deriving the integral representation of a fractional Hankel transform from a
      fractional Fourier transform.
AB  - We derive the integral representation of a fractional Hankel transform (FRHT)
      from a fractional Fourier transform. Some basic properties of the FRHT such as
      Parseval's theorem and its optical implementation are discussed qualitatively.

PMID- 18087460
TI  - High-average-power KTiOAsO4 optical parametric oscillator.
AB  - Using noncritically phase-matched 1-cm(2) -aperture KTiOAsO(4) (KTA) crystals in
      an optical parametric oscillator (OPO), we have demonstrated a sustained average
      signal power of 33 W at 1534.7 nm. To our knowledge, this is the highest-average
      power signal ever generated by an OPO. The pump source was a 100-Hz Q -switched
      1064-nm Nd:YAG laser. Compared with that of the similar and more-common material
      KTiOPO>(4) , idler absorption in KTA is negligible, allowing high-power operation
      with minimal thermally induced refractive distortion in the OPO crystal.

PMID- 18087461
TI  - Photorefractive two-step recording in a piezoelectric La3Ga5SiO14 crystal doped
      with praseodymium.
AB  - The first experimental verification to the authors' knowledge of efficient two
      step recording in a photorefractive and piezoelectric crystal of
      La(3)Ga(5)SiO(14):Pr(3+) with cw laser light (I<20 W/cm(2)) is reported. We found
      nonlinear behavior of the photorefractive sensitivity and photovoltaic current,
      indicating that the excitation process is connected to excitation of 4f(2)
      electrons of the Pr(3+) dopant through an intermediate level to the conduction
      band. This two-step nature of the photorefractive effect makes the crystal an
      exciting new candidate for applications in holographic storage.

PMID- 18087462
TI  - Walk-off and pattern selection in optical parametric oscillators.
AB  - The effect of walk-off in pattern selection in optical parametric oscillators is
      theoretically examined. We show that a dynamic mechanism also allows us to
      observe the formation of structures for positive signal detunings. In this regime
      the pattern that is generated is a periodic array of kinks that separate regions
      in which one of two stable steady states is alternately selected. This structure
      can be regarded as a train of dark soliton stripes because the two solutions have
      opposite signs. The wavelength of the selected pattern is theoretically
      predicted, and the prediction agrees with the results of the numerical solutions
      of the equations governing the device.

PMID- 18087463
TI  - Visualization of the nonlinear optical space-charge region of bulk thermally
      poled fused-silica glass.
AB  - We etched thermally poled fused-silica coverslips in 49% HF for 30 s transverse
      to the poling direction to reveal structural details of the nonlinear region. A
      peaked ridge below the anode surface, corresponding to a slower etch rate than
      that of the bulk SiO(2) , was located approximately 5 microm below the anode
      surface for a poling time of 30 s. The ridge moved deeper into the glass
      logarithmically with poling time. This trend is qualitatively consistent with a
      recent model for the formation of the space-charge region that includes injection
      of hydrogen ions at the anode surface.

PMID- 18087464
TI  - Beam coupling induced transparency in a bacteriorhodopsin-based saturable
      absorber.
AB  - The nonlinear coupling of two beams in a saturable absorber is shown to cause a
      strong enhancement of the beams' transmissivity. An analysis of this beam
      coupling effect and its experimental demonstration with bacteriorhodopsin are
      given.

PMID- 18087465
TI  - Anisotropy, nonlocality, and space-charge field displacement in (2 + 1)
      dimensional self-trapping in biased photorefractive crystals.
AB  - The complete basic equations for (2+1) -dimensional self-trapped beam propagation
      in photorefractive media are numerically solved, with the anisotropic nonlocal
      response, diffusion, and space-charge-field displacement effects taken into
      account. Initial Gaussian beams show elliptical beam shapes, self-deflection, and
      long-lived oscillations after propagation. The critical parameters that determine
      the possible damping of the transients are discussed.

PMID- 18087466
TI  - Mode-partition noise interferometric conversion function.
AB  - We derive expressions that describe the maximum and minimum envelopes of mode
      partition noise converted into intensity noise through an unbalanced
      interferometer, using a simple model of a multimode laser diode, and
      experimentally confirm the expressions.

PMID- 18087467
TI  - Long-range soliton interactions in dispersion-managed links.
AB  - A numerical analysis of soliton propagation in a dispersion-compensated
      transmission system reveals the presence of a small dispersive-wave contribution
      to the propagating soliton that increases dramatically whenever the input soliton
      energy is detuned from its optimal value. A straightforward consequence of the
      dispersive-wave emission is an unexpectedly strong contribution to the long-range
      soliton-soliton interaction. We show that the combination of long- and short
      range interactions induces soliton timing jitter that grows larger than that
      which arises from the Gordon-Haus effect.

PMID- 18087468
TI  - Electrostriction-induced acoustic effect in ultralong-distance soliton
      transmission systems.
AB  - The electrostriction-induced acoustic effect introduces a time-dependent index
      evolution for the following optical pulses and results in an additional temporal
      shift of solitons. The acoustic effect is incorporated into the nonlinear
      Schrodinger equation as a perturbative term. We investigate the evolution of
      timing jitter, taking into account both the Gordon-Haus and the acoustic effect
      contributions for a 10-Gbit/s sliding-frequency in-line-filter soliton system.

PMID- 18087469
TI  - Demonstration of microwave frequency shifting by use of a highly chirped mode
      locked fiber laser.
AB  - We report an experimental demonstration of a photonic microwave shifter using a
      highly chirped mode-locked fiber laser. The system is based on dispersive
      compression or expansion of highly chirped optical pulses that are amplitude
      modulated by the microwave signal. Using this technique, we demonstrated
      frequency shifting of a microwave signal from 10 GHz down to 5 GHz and up to 25
      GHz.

PMID- 18087470
TI  - Analytical description of cross-phase modulation in dispersive optical fibers.
AB  - The effect of intensity distortion induced by cross-phase modulation in
      dispersive optical fibers is studied. It is shown that, in most configurations in
      which distortions that are due to cross-phase modulation can become significant
      to optical communications, the effect of cross-phase modulation can be described
      with excellent accuracy by simple analytical expressions. The presented analysis
      also suggests that intensity distortions owing to cross-phase modulation can be
      efficiently reduced by linear dispersion compensation.

PMID- 18087471
TI  - Integrated optical Ti:Er:LiNbO3 distributed Bragg reflector laser with a fixed
      photorefractive grating.
AB  - For the first time to the authors' knowledge, an integrated optical distributed
      Bragg reflector laser with a fixed photorefractive grating in LiNbO(3) is
      demonstrated. Sample preparation, grating fabrication, and laser characteristics
      are reported. The device is pumped by a fiber pigtailed laser diode (lambda(p)
      approximately 1480 nm) through the Bragg grating in a double-pass configuration,
      yielding an emission in the backward direction at lambda=1531.7 nm . The laser
      threshold is 40 mW; as much as 5 mW of output power has been obtained at 110 mW
      of launched pump power in cw operation.

PMID- 18087472
TI  - Effects of ion clusters on the performance of a heavily doped erbium-doped fiber
      laser.
AB  - A cluster model is proposed for study of the effects of the number of ions per
      cluster on the performance of a heavily erbium-doped fiber laser. The results
      indicate that both the threshold pump power and the unstable-operation region of
      the fiber laser increase with increasing numbers of ions per cluster.

PMID- 18087473
TI  - Single-frequency, single-polarization operation of tunable miniature
      erbium:ytterbium fiber Fabry-Perot lasers by use of self-injection locking.
AB  - We demonstrate successful single-frequency, single-polarization operation of
      erbium:ytterbium fiber Fabry-Perot lasers with frequency- and polarization
      selective optical feedback, using a fiber Bragg grating and a polarizer. Side
      mode suppression greater than 60>dB and pure single-polarization operation were
      achieved.

PMID- 18087474
TI  - Analysis of an intracavity-doubled diode-pumped Q-switched Nd:YAG laser producing
      more than 100 W of power at 0.532 microm.
AB  - A diode-pumped Nd:YAG laser was frequency doubled to 0.532 microm with an
      intracavity KTiOPO(4) crystal in a V-cavity arrangement, achieving an output
      power of 140 W. Acousto-optic Q switching was employed at repetition rates of 10
      30 kHz, and the beam quality was assessed at M(2) approximately 50. It was
      deduced on the basis of our model that the strength of the nonlinear frequency
      conversion is the main parameter determining the pulse width.

PMID- 18087475
TI  - Analysis of the fast recovery dynamics of a semiconductor laser with feedback in
      the low-frequency fluctuation regime.
AB  - We experimentally investigate the temporal evolution of the power of an external
      cavity semiconductor laser in the low-frequency fluctuation regime with
      subnanosecond resolution. We show, for the first time to our knowledge, that
      generally the laser power drops to a value significantly different from the
      solitary laser power. We demonstrate the analogy between the recovery of the
      laser intensity and the turn-on transient of a semiconductor laser.

PMID- 18087476
TI  - Three-dimensional second-harmonic generation imaging with femtosecond laser
      pulses.
AB  - A three-dimensional reflectance scanning optical microscope based on the
      nonlinear optical phenomenon of second-harmonic generation is presented. A mode
      locked Ti:sapphire laser producing <90-fs pulses at approximately 790 nm was
      used, and the images were constructed by scanning of an object, which possessed
      local second-order nonlinearity, relative to a focused spot from the laser. The
      second-harmonic light at approximately 395 nm generated by the specimen was
      separated from the fundamental beam by use of dichroic and interference filters
      and was detected by a photodiode. The technique was then used to characterize the
      distribution of second-order nonlinearity and microstructure of the nonlinear
      material lithium triborate.

PMID- 18087477
TI  - Ultrashort-pulse-controlled all-optical modulation by interband and intersubband
      transitions in doped quantum wells.
AB  - The optimum condition for achieving highly efficient ultrafast all-optical pulse
      modulation by modification of the absorption of a pulsed interband light field by
      ultrasubband control-light pulses in a doped quantum well is investigated. The
      modulation efficiency in the femtosecond domain can be maximized by an
      intersubband control light with a pulse width (200 fs) that is comparable with
      the phase-relaxation time of the system and an intensity that is close to the
      intersubband saturation intensity.

PMID- 18087478
TI  - Photon-counting technique for rapid fluorescence-decay measurement.
AB  - We report on a novel laser-induced fluorescence triple-integration method
      (LIFTIME) that is capable of making rapid, continuous fluorescence lifetime
      measurements by a unique photon-counting technique. The LIFTIME has been
      convolved with picosecond time-resolved laser-induced fluorescence, which employs
      a high-repetition-rate mode-locked laser, permitting the eventual monitoring of
      instantaneous species concentrations in turbulent flames. We verify the technique
      by application of the LIFTIME to two known fluorescence media, diphenyloxazole
      (PPO) and quinine sulfate monohydrate (QSM). PPO has a fluorescence lifetime of
      1.28 ns, whereas QSM has a fluorescence lifetime that can be varied from 1.0 to
      3.0 ns. From these liquid samples we demonstrate that fluorescence lifetime can
      currently be monitored at a sampling rate of up to 500 Hz with less than 10%
      uncertainty (1 sigma) .

PMID- 18087479
TI  - Gray-scale data pages for digital holographic data storage.
AB  - The prospects for gray-scale (or multilevel) digital holographic data storage are
      theoretically and experimentally investigated. A simple signal-to-noise ratio
      (SNR) partitioning argument shows that when SNR scales as 1 over the number of
      holograms squared, five gray levels (log(2) 5 bits/pixel) would be expected to
      result in a 15% capacity increase over binary data pages. However, the additional
      signal-dependent noise sources present in practical systems create a baseline SNR
      that reduces both the optimal number of gray levels and the resulting gain in
      capacity. To implement gray-scale recording experimentally, we adapt the
      predistortion technique previously developed for binary page-oriented memories
      [Opt. Lett. 23, 289 (1998)]. Several new block-based modulation codes for
      decoding gray-scale data pages are introduced. User capacity is evaluated by an
      experimental technique using LiNbO(3) :Fe in the 90 degrees geometry.
      Experimental results show that a balanced modulation code with three gray levels
      provides a 30% increase in capacity (as well as a 30% increase in readout rate)
      over local binary thresholding.

PMID- 18087480
TI  - Three-dimensional microscopy with phase-shifting digital holography.
AB  - We applied phase-shifting digital holography to microscopy by deriving the
      complex amplitude of light scattered from microscopic three-dimensional objects
      through a microscope objective by video camera recording, phase-shifting
      analysis, and computer reconstruction. This method requires no mechanical
      movement and provides a flexible display and quantitative evaluation of the
      reconstructed images. A theory of image formation and experimental verification
      with specimens are described.

PMID- 18087481
TI  - Enhancement of the wavelength selectivity of a volume hologram by use of
      multimode optical fiber referencing.
AB  - Wavelength multiplexing of a volume hologram was combined with multimode fiber
      referencing. A photorefractive volume hologram was recorded and probed by
      reference light diffracted from a multimode optical fiber. A tunable laser diode
      was used as a light source that was launched into the multimode fiber. As the
      wavelength of the source laser shifted, the speckle patterns from the multimode
      fiber changed. The wavelength selectivity of the volume hologram was enhanced by
      the combined effect of wavelength change and speckle change.

PMID- 18087482
TI  - Flexible hollow waveguides for delivery of excimer-laser light.
AB  - A hollow waveguide consisting of a glass tube with a thin aluminum film on the
      inner surface is proposed for delivery of excimer-laser light. The waveguide,
      fabricated by a chemical-vapor-deposition method, shows low losses for KrF
      excimer laser light: the straight loss of a 1-mm-bore waveguide was 0.4 dB:m.

PMID- 18087483
TI  - Subkilohertz enhanced-power diode-laser spectrometer in the visible.
AB  - We report on a high-performance diode-laser spectrometer operating near 657 nm
      with narrow linewidth (<0.6 kHz) , enhanced power (as much as 40 mW), and low
      drift (<10 Hz/s) . The spectrometer comprised an extended-cavity diode-laser
      frequency stabilized to a high-finesse optical resonator and a broad-area
      antireflection coated laser diode as an amplifier with a single-lobe emission
      pattern of good spatial purity. The spectrometer was used to record time-domain
      optical Ramsey spectra of laser-cooled Ca atoms with a resolution of 0.6 kHz.

PMID- 18087484
TI  - Fabrication of spatial walk-off polarizing film exhibiting a large split angle by
      oblique silicon deposition.
AB  - A spatial walk-off polarizing film with a large split angle was fabricated by use
      of the oblique deposition method. The film is composed of slanted needlelike
      microcolumns of a-Si that are separated by resultant fine voids. The polarization
      splitting characteristics of the film were clearly observed. The maximum split
      angle at a wavelength of 1.55 microm was as large as 20 degrees , more than three
      times greater than those of existing polarizers such as those constructed of
      rutile and calcite.

PMID- 18087485
TI  - Optical fiber photoacoustic-photothermal probe.
AB  - We describe the operation of an all-optical probe that provides an alternative
      means of implementing photoacoustic and photothermal investigative techniques,
      particularly those used in biomedical applications. The probe is based on a
      transparent, acoustically and thermally sensitive Fabry-Perot polymer film sensor
      mounted at the end of an optical fiber. We demonstrate the ability of the system
      to make photoacoustic and photothermal measurements simultaneously and evaluate
      its photothermal response, using a nonscattering liquid target of known and
      adjustable absorption coefficient. The acoustic and thermal noise floors were 2
      kPa and 6 x 10(-3) degrees C , respectively, obtained over a 25-MHz measurement
      bandwidth and 30 signal averages.

PMID- 18087486
TI  - Two-photon near- and far-field fluorescence microscopy with continuous-wave
      excitation.
AB  - We report on scanning far- and near-field two-photon microscopy of cell nuclei
      stained with DAPI and bisbenzimidazole Hoechst 33342 (BBI-342) with the 647-nm
      laser line of a cw ArKr mixed-gas laser. Two-photon-excited fluorescence images
      are obtained for 50-200 mW of average power at the sample. A nearly quadratic
      dependence of fluorescence intensity on laser power confirmed the two-photon
      effect. The nonlinearity was further supported by evidence of three-dimensional
      sectioning in a scanning far-field microscope. We find that the cw two-photon
      irradiation sufficient for imaging within typically 5 s does not significantly
      impair cell cycling of BBI-342-labeled live cells. Finally, high-resolution
      imaging in scanning near-field microscopy with good contrast is demonstrated.

PMID- 18087487
TI  - Propagation-invariant spot arrays.
AB  - Optical fields with scale- and shape-invariant transverse intensity profiles
      consisting of a prescribed distribution of bright spots are introduced.
      Approximations of such fields are demonstrated by means of binary annular
      aperture diffractive elements.

PMID- 18087488
TI  - Jitter suppression by guiding filters in combination with dispersion management.
AB  - Enhancement of jitter suppression of a soliton by combination of fixed-frequency
      filters with periodic dispersion compensation is predicted in an analytical form
      by means of the Fokker-Planck equation for the soliton's random walk. The result
      depends on the dispersion-compensation period but not on the ratio of the
      dispersions. Another result is presented that can help one to understand jitter
      suppression by dispersion compensation without filters, which was observed in
      recent experiments.

PMID- 18087489
TI  - Photorefractive properties of Cu-doped KNSBN crystal with fluorine replacing
      oxygen.
AB  - We report the photorefractive properties of a new kind of Cu-doped KNSBN crystal
      in which a small fraction of oxygen (O) atoms are replaced with fluorine (F)
      atoms. The replacement of oxygen with fluorine in Cu:KNSBN crystals leads to a
      much shorter response time of 30 ms at an incident intensity of 5 W/cm(2). We
      also discuss the effect of electron-hole competition on the coupling constant.

PMID- 18087490
TI  - Guiding-center walking soliton.
AB  - The concept of the guiding-center walking soliton is introduced for examination
      of self-trapping of light in quadratic nonlinear media in materials with large
      Poynting vector walk-off. It is shown that robust guiding-center solitons exist
      in properly constructed tandem structures. The goal is to form quadratic solitons
      with reduced light intensities.

PMID- 18087491
TI  - Low-threshold, self-frequency-stabilized AgGaS(2) continuous-wave subharmonic
      optical parametric oscillator.
AB  - We report the demonstration of a cw AgGaS(2) optical parametric oscillator (OPO).
      The subharmonic (3omega ? 2omega + omega) OPO is configured as a doubly resonant
      oscillator with weak pump enhancement. The temperature-tuned, noncritically phase
      matched crystal is pumped by a diode laser at lambda(p) approximately 845 nm .
      Oscillation at lambda(s) approximately 1267 nm and lambda(i) approximately 2535
      nm is observed at an input threshold power of 60 mW. Crystal thermal loading
      induces a robust passive self-frequency stabilization of any single-axial-mode
      pair to the OPO cavity resonance. The conversion efficiency is limited by thermal
      effects to 2% for a 200-mW pump input.

PMID- 18087492
TI  - Coupled tandem optical parametric oscillator (OPO): an OPO within an OPO.
AB  - We have demonstrated, for the first time to our knowledge, a coupled tandem
      optical parametric oscillator (OPO) configuration in which a second ZnGeP(2) OPO
      is placed within the resonator of the first, KTiOPO(4), OPO. A significant
      enhancement in the overall cascaded efficiency of this OPO compared with standard
      two-stage OPO's was observed. With a multimode Nd:YAG laser, an overall optical
      to-optical efficiency (from 1.06 microm to the mid IR) of 5.2% was obtained from
      operating only ~1.4 times above oscillation threshold. The measured overall slope
      efficiency was attractively high at 35%. With a single set of mirrors we obtained
      a broad wavelength-tuning range from 2.7 to 8 microm.

PMID- 18087493
TI  - Existence, bistability, and instability of Kerr-like parametric gap solitons in
      quadratic media.
AB  - We investigate the existence and stability of parametric gap solitons in chi((2))
      media in the limit of Kerr-equivalent nonlinearities. We reveal soliton branching
      (bistability) described by an explicit criterion. Unlike in other optical
      solitons, both branches of gap solitons can be unstable owing to oscillatory
      instabilities. Despite these mechanisms stable gap solitons do exist.

PMID- 18087494
TI  - Nonlinear theory of soliton-induced waveguides.
AB  - We develop a nonlinear theory of soliton-induced waveguides that describe a
      finite-amplitude probe beam guided by a spatial dark soliton in a saturable
      nonlinear medium. We suggest an effective way to control the interaction of these
      soliton-induced waveguides and also show that, in sharp contrast with scalar dark
      solitons, the dark-soliton waveguides can attract each other and even form
      stationary bound states.

PMID- 18087495
TI  - 100-Gbit/s bitwise logic.
AB  - We demonstrate 100-Gbit/s bitwise logic in an all-optical semiconductor optical
      amplifier-based switching device, the ultrafast nonlinear interferometer. To the
      best of our knowledge this is the first demonstration of 100-Gbit/s AND and
      INVERT functionality with a 100-GHz optical clock stream and a 100-Gbit/s data
      stream as the logical inputs to a semiconductor-based switch. Additionally, 100
      Gbit/s inverting and noninverting all-optical wavelength conversion are
      demonstrated.

PMID- 18087496
TI  - Continuous-wave measurement of the fiber nonlinear refractive index.
AB  - We propose a technique for measuring the nonlinear refractive index of fiber
      based on transmission-coefficient measurements in a fiber Sagnac interferometer.
      In contrast with traditional methods, the proposed method uses a single optical
      source operating in cw mode and direct intensity measurement, enabling one to
      avoid the errors caused by fiber dispersion and uncertainty of spectral peak
      difference measurements that occur with pulse-based methods. The nonlinear
      refractive index in 20-mol. % GeO(2) fiber was measured to be (3.1 +/- 0.2) x 10(
      16) cm(2) W(-1) at 1064 nm.

PMID- 18087497
TI  - Accurate tuning of mismatched twin-core fiber filters.
AB  - We have demonstrated a reproducible and accurate way of tuning the coupling
      wavelength of a mismatched twin-core filter. This method allows high quality all
      fiber filters to be implemented with low loss at any desired wavelength over a
      range of few hundred nanometers from the same fiber. An ~500-nm tuning range is
      demonstrated, limited only by the measurement setup and not by the technique
      itself. Highly accurate control of the filtering wavelength in combination with
      control of filtering strength by adjustment of the length of the twin-core fibers
      allows complex filter profiles to be implemented by cascading of several
      different filters. These filters are also very stable to a change in temperature
      (~0.26 nm/100 degrees C at 1.55 microm) and strain (less than 0.3 nm/mstrain at
      1.55 microm), permitting easy packaging.

PMID- 18087498
TI  - Laser frequency stabilization by means of optical self-heterodyne beat-frequency
      control.
AB  - We propose and demonstrate a novel frequency-stabilization scheme that provides
      linewidth narrowing and at the same time is compatible with high-speed frequency
      agility. The method relies on sensing and control of a heterodyne beat signal
      derived from a fiber interferometer and functions in the absence of a fixed
      reference frequency. Our demonstration utilizes a short-external-cavity diode
      laser equipped with an intracavity electro-optic crystal for frequency
      correction. The stabilization method is shown to suppress impressed laser
      frequency modulation by nearly 2 orders of magnitude. Without further
      modification of our scheme we also demonstrate laser frequency tuning control.

PMID- 18087499
TI  - Sub-8-fs pulses from an ultrabroadband optical parametric amplifier in the
      visible.
AB  - Pulses with 180-THz bandwidth and 2-microJ energy were generated by a
      noncollinear optical parametric amplifier in the visible, pumped by the second
      harmonic of a Ti:sapphire laser. A portion of the amplified pulse spectrum was
      compressed to 7.2 fs by use of a thin prism sequence.

PMID- 18087500
TI  - Nonlinear source for the generation of high-energy few-cycle optical pulses.
AB  - We investigate the evolution of optical pulses in a hollow waveguide filled with
      noble gas at pulse intensities for which tunnel ionization dominates the
      nonlinear response of the gas. A numerical analysis reveals that the spectral
      chirp generated by the plasma nonlinearity is to a good approximation linear over
      the whole pulse spectrum and can be compensated in a dispersive delay line. Our
      calculations predict the generation of 3-4-fs optical pulses with energies of a
      few milijoules. To our knowledge, these energies are an order of magnitude
      greater than the pulse energies that have been realized to date in hollow-fiber
      compressors based exclusively on the nonlinear Kerr effect.

PMID- 18087501
TI  - Reduced-background gas-phase absorption spectroscopy.
AB  - We propose and demonstrate a new method for single-shot multiplex absorption
      spectroscopy that permits enhanced sensitivity in the simultaneous measurement of
      multiple spectral lines in rapidly changing gas-phase media, such as turbulent
      flames. It uses an ultrashort laser pulse that propagates through the absorbing
      medium, for which the relevant absorption information resides in the free
      induction decay that is trailing behind the transmitted pulse. Time gating out
      most of the transmitted pulse, but not the free-induction decay, enhances the
      relative fraction of light that contains absorption information when the spectrum
      is measured. This procedure reduces the background associated with the input
      light, thus enhancing detection sensitivity.

PMID- 18087502
TI  - Pulse-front-matched optical parametric amplification for sub-10-fs pulse
      generation tunable in the visible and near infrared.
AB  - A noncollinear optical parametric amplifier is presented that generates transform
      limited sub-10-fs pulses that are tunable in both the visible and the near
      infrared (NIR). The pulse-front-matched pump geometry realizes tilt-free signal
      amplification, and pulses as short as 6.1 fs can be obtained from 550 to 700 nm.
      The large angular dispersion of the idler specific to the group-velocity-matching
      interaction is effectively eliminated by a grating-telescope compensator, and 9
      fs NIR pulses are also successfully obtained from 900 to 1300 nm. This is
      believed to be the first tunable sub-10-fs light source.

PMID- 18087503
TI  - Saturable absorption in poly(indenofluorene): a picket-fence polymer.
AB  - Poly(indenofluorene) shows a strong degenerate four-wave mixing (DFWM) response
      when it is excited with 100-fs pulses at 800 nm. The DFWM signal scales with the
      1.5 power of the input intensity, which we interpret as being due to absorption
      saturation phenomena. The saturation was studied by open-aperture Z scan in
      dilute solutions of poly(indenofluorene) in chloroform. The changes in the
      absorption coefficient alpha are described by the formula alpha = alpha(0)/[1 +
      (I/I(sat))(1/2)], where I(sat) is the saturation intensity, which is found to be
      of the order of 100>MW/cm(2).

PMID- 18087504
TI  - Simultaneous spatial and temporal walk-off compensation in frequency-doubling
      femtosecond pulses in beta-BaB(2)O(4).
AB  - We experimentally demonstrate the benefits of simultaneous compensation of
      spatial and temporal walk-off in frequency doubling of 800-nm 250-fs pulses,
      using three active and two compensating beta-BaB(2)O(4) crystals. The
      compensating crystals reverse both birefringent and group-velocity walk-off,
      resulting in a factor-of-4.5 improvement in doubling efficiency relative to one
      of the active crystals while maintaining the short pulse duration and the
      symmetric spatial profile that are characteristic of the single crystal.

PMID- 18087505
TI  - Time-domain observation of optical pulse propagation in whispering-gallery modes
      of glass spheres.
AB  - We report picosecond time-resolved measurements of optical pulse propagation in
      dielectric spheres (8, 10, and 26 mm in diameter) for which the pulse duration (
      approximately 2 ps) was short compared with the equatorial round-trip time within
      the sphere. A size-independent buildup of the leakage intensity in terms of the
      number of round trips was observed for each of the spheres, as were damped low
      frequency oscillations superimposed upon the pulse ringdown envelope. These
      features of the data are interpreted as resulting from perturbative coupling of
      eigenmodes of the sphere and trajectory precession near the observation region.

PMID- 18087506
TI  - Three-dimensional memory effect in fluorescent photosensitive glass activated by
      europium and cerium.
AB  - The persistent extinction of fluorescence emission of Eu(3+) in glasses activated
      with europium and cerium is reported for the first time to the authors'
      knowledge. The glass samples containing Eu(3+) and Ce(3+) were initially
      colorless and transparent and exhibited intense emission peaks at 592 and 612 nm
      assigned to the (5)D(0)-(7)F(1, 2) transitions of Eu(3+). The complete extinction
      of the Eu(3+)-ion emission was obtained as an effect of multipulse excimer-UV
      laser (lambda = 248 nm, tau(FWHM) >/= 20 ns) irradiation of the glass samples.
      Fluorescence microscopy, Mossbauer spectrometry, and electron spin resonance were
      applied for investigation of the modifications induced by the laser treatment. As
      a decisive proof of the extinction of fluorescence we succeeded in recording
      three-dimensional fluorescent photographic patterns within the activated samples.

PMID- 18087507
TI  - High-efficiency volume hologram recording with a pulsed signal beam.
AB  - We present an efficient photorefractive volume hologram recording technique with
      a pulsed signal beam and continuous reference-beam illumination. The grating
      envelope can be simply controlled by manipulation of the duty cycle of the signal
      beam. Thus, for any grating coupling strength and different initial reference
      signal intensity ratios, the diffraction efficiency can be maximized with this
      technique and can be greatly increased in comparison with that of the
      conventional recording technique.

PMID- 18087508
TI  - Characterization of phenanthrenequinone-doped poly(methyl methacrylate) for
      holographic memory.
AB  - The holographic recording characteristics of phenanthrenequinone- (PQ-) doped
      poly(methyl methacrylate) are investigated. The exposure sensitivity is
      characterized for single-hologram recording, and the M/# is measured for samples
      as thick as 3 mm. Optically induced birefringence is observed in this material.

PMID- 18087509
TI  - Phase-sensitivity measurement of a 10-sensor array with erbium-doped fiber
      amplifier telemetry.
AB  - We report what are believed to be the first measurements of the phase sensitivity
      of a fiber sensor array using multiple low-gain remotely pumped amplifiers with
      an interferometric sensor inserted. The measured phase sensitivities for
      individual rungs average 5.7 microrad(rms)/ radicalHz and exhibit no dependence
      on rung number, in agreement with predictions.

PMID- 18087510
TI  - Thermal grating velocimetry.
AB  - A method is reported for time- and space-resolved nonintrusive velocimetry of
      high-speed gas flows by measurement of the Doppler shift of light scattered from
      a laser-induced thermal grating. The principle is demonstrated by use of a pulsed
      frequency-doubled Nd:YAG laser to induce a thermal grating in NO(2) seeded into
      an argon flow. Signals are generated by Bragg scattering of probe beams at the
      fundamental frequency of the same Nd:YAG laser. Flow velocities in the range 30
      180 ms(-1) are measured, in agreement with values obtained with a Pitot tube. The
      measurement uncertainties obtained indicate that a precision of 1% is feasible
      for flows at Mach 1.

PMID- 18087511
TI  - Optical heterodyne detection of laser-induced gratings.
AB  - A novel optical arrangement for heterodyne detection of laser-induced gratings
      based on the use of a phase mask for both excitation and probe beams provides
      phase stability and control without the need for an active stabilization scheme.
      The arrangement greatly simplifies the laser-induced grating experiment. The
      performance of the technique in both transmission and reflection geometries is
      illustrated through measurements of bulk and surface acoustic waves generated by
      picosecond laser pulses.

PMID- 18087512
TI  - Transverse grating-assisted narrow-bandwidth acousto-optic tunable filter.
AB  - An experimental acousto-optic tunable filter that has a narrow spectral bandwidth
      (0.2 nm at 1550 nm) and a fast (10-micros) tuning capability with a continuous
      tuning range of approximately 50 nm is described. The tunable filter consists of
      an acousto-optic beam deflector with a diffraction grating whose grating vector
      is transverse to the direction of light propagation.

PMID- 18087513
TI  - Solid phase formation of silicon nanocrystals by bulk ultrafast laser-matter
      interaction.
AB  - Ultrashort pulse laser interaction with silica-silicon interfaces is presented as
      a means for all-solid-phase formation of high-purity silicon nanoparticles in the
      absence of ablation plumes or any substrate intermixing with surfaces in ambient
      air. Transmission electron microscopy and Raman spectroscopy provide definitive
      evidence for creation of nanocrystals in the silica host, while compressive
      stress in the silicon substrate corroborates the formation of optical waveguides
      parallel to the tracks.

PMID- 18087514
TI  - Evolution and termination of a femtosecond laser filament in air.
AB  - The evolution of the filamentation of a femtosecond laser pulse in air is
      measured. The divergence of the filament core is almost constant over a long
      distance, encompassing a zone with efficient ionization followed by another where
      ionization is much weaker. At the end, the core diverges out linearly with a low
      divergence due to self-spatial filtering.

PMID- 18087515
TI  - Simultaneous fast and slow light in microring resonators.
AB  - Two orthogonal light polarizations in a waveguide overcoupled to microring
      resonators can propagate as fast and slow light. Which polarization is fast
      (slow) is determined by input polarization and the number of resonators.

PMID- 18087516
TI  - Application of correlation-induced spectral changes to inverse scattering.
AB  - It is shown how the phenomenon of correlation-induced spectral changes generated
      on scattering of a polychromatic plane wave on a spatially homogeneous random
      medium may be used to determine the correlation function of the scattering
      potential of the medium.

PMID- 18087517
TI  - Microwave pulse phase encoding using a photonic microwave delay-line filter.
AB  - A novel technique to perform microwave pulse phase encoding using an incoherent
      photonic microwave delay-line filter is proposed and experimentally demonstrated.
      Being different from a regular microwave delay-line filter, in which the time
      delay differences are identical between any adjacent taps, the proposed filter
      has nonidentical time-delay differences. A phase-encoded microwave pulse with the
      required code pattern is generated by properly adjusting the time-delay
      differences. The chip number of a generated phase code is determined by the
      number of the filter taps, and the phase shift of each chip is determined by the
      corresponding time-delay difference. The proposed technique is verified by
      experiments. The generation of binary and quaternary phase-coded pulses is
      experimentally demonstrated.

PMID- 18087518
TI  - Continuous tunable laser operation in both the 1.31 and 1.55 microm
      telecommunication windows in LiIn(Si/Ge)O4 olivines doped with trivalent
      chromium.
AB  - An ultrawide tuning range from 1160 to 1620 nm for LiInSiO(4) and from 1150 to
      1600 nm for LiInGeO(4) crystals has been demonstrated. This is the widest
      bandwidth and the most near-infrared shifted wavelength range for laser operation
      ever demonstrated for the Cr(3+) ion. For what is believed to be the first time
      tunable laser operation was achieved for both the 1.33 and 1.55 microm
      telecommunication windows from a single optical center.

PMID- 18087519
TI  - Holography: an interpretation from the phase-space point of view.
AB  - The formation of holograms is interpreted as the consequence of the bilinearity
      of the ambiguity function. Reconstruction can then be regarded as the
      manipulation of the ambiguity function. Specifically, we show that in the case of
      in-line holography, the reconstruction can be regarded as phase tomography. In
      this way we provide a unified picture for the formulation of both
      noninterferometric and interferometric phase-retrieval techniques.

PMID- 18087520
TI  - Millijoule pulse energy high repetition rate femtosecond fiber chirped-pulse
      amplification system.
AB  - We report on an ytterbium-doped fiber chirped-pulse amplification (CPA) system
      delivering millijoule level pulse energy at repetition rates above 100 kHz
      corresponding to an average power of more than 100 W. The compressed pulses are
      as short as 800 fs. As the main amplifier, an 80 microm core diameter short
      length photonic crystal fiber is employed, which allows the generation of pulse
      energies up to 1.45 mJ with a B-integral as low as 7 at a stretched pulse
      duration of 2 ns. A stretcher-compressor unit consisting of dielectric
      diffraction gratings is capable of handling the average power without beam and
      pulse quality distortions. To our knowledge, we present the highest pulse energy
      ever extracted from fiber based femtosecond laser systems, and a nearly 2 orders
      of magnitude higher repetition rate than in previously published millijoule-level
      fiber CPA systems.

PMID- 18087521
TI  - Photosensitivity-enabled dispersion controllability for quasi-phase-matching in
      photonic crystal fibers.
AB  - A novel photonic crystal fiber featured by concentric cores is proposed to induce
      dispersion controllability by photosensitivity. Chromatic dispersion can be
      changed from -1827 to 72 ps/nm/km with refractive index modulation of 4 x 10(-4)
      produced in Ge-doped regions in the fiber. Effective mode area of inner mode is
      as small as 6.4 mum(2). The proposed fiber enables to achieve quasi-phase-matched
      nonlinear parametric interaction in a single piece of photonic crystal fiber, by
      periodically alternating dispersion and compensating for phase mismatching caused
      by the dispersion.

PMID- 18087522
TI  - Efficient skew-angle cladding-pumped tunable narrow-linewidth Yb-doped fiber
      laser.
AB  - A skew-angle cladding-pumped tunable Yb-doped fiber laser is presented. The laser
      was tunable over more than 30 nm, from 1022 to 1055 nm, by employing a volume
      Bragg grating in a retroreflector configuration as one of the cavity delimiters.
      Output powers in excess of 4.3 W were recorded with a spectral bandwidth of 5 GHz
      and an M(2) value below 1.3 over the whole tuning range.

PMID- 18087523
TI  - Attosecond relative timing jitter and 13 fs tunable pulses from a two-branch
      Er:fiber laser.
AB  - We present what is believed to be the first direct measurement of the relative
      timing jitter between the two parallel pulse trains of a two-branch femtosecond
      erbium-doped fiber laser, operated without active stabilization. The system
      provides independently tunable pulses in the near infrared with durations down to
      13 fs. Using an interferometric optical cross-correlator, the phase-noise
      spectral density is measured with high sensitivity in a range from 1 Hz up to the
      Nyquist frequency of 24.5 MHz. We find an integrated jitter of 11 attoseconds
      directly after the amplifier stages and 43 as after propagation through free
      space optics and nonlinear fibers for frequency conversion.

PMID- 18087524
TI  - Method of reconstructing wavefront aberrations from the intensity measurement.
AB  - A method for reconstructing wavefront aberrations from intensity measurements in
      the focal plane of a focusing optic is presented. This reconstruction method is
      simple, fast, and accurate in reconstructing wavefront aberrations because it
      uses the inverse Fourier transform of an intensity distribution in the focal
      plane with a reference electric field. The validity of the reconstruction method
      is demonstrated by computing a wavefront aberration from the intensity
      distributions in the focal plane.

PMID- 18087525
TI  - Fixed index gratings in LiNbO(3):Fe upon long-term exposure to an intense laser
      beam.
AB  - Permanently fixed noisily recorded refractive index gratings are discovered in
      single crystals of LiNbO(3):Fe upon long-term exposure to a single laser beam
      with high intensities of I=100 kW/m(2) and ambient temperature. The fixing
      process is explained by considering the effect of laser-induced heating of the
      sample and the well-known simultaneous thermal fixing procedure.

PMID- 18087526
TI  - 10 GHz regeneratively mode-locked semiconductor optical amplifier fiber ring
      laser and its linewidth characteristics.
AB  - A 10 GHz regeneratively mode-locked semiconductor optical amplifier fiber ring
      laser with a picosecond pulse duration was newly constructed, and the linewidth
      change of a longitudinal mode was measured for various laser cavity lengths using
      a delayed self-heterodyne detection method. The detected line shape was
      approximately Gaussian for cavity lengths of 3.4-171 m. This result indicates
      that the laser linewidth depends strongly on thermal or acoustic cavity length
      fluctuations. The linewidth was proportional to the inverse square root of the
      cavity length, and a linewidth of 1.7 kHz was obtained for a cavity length of 171
      m.

PMID- 18087527
TI  - Pedestal suppression of ultrashort pulses by using a birefringent nonlinear
      polarization rotation mirror.
AB  - A new scheme for a birefringent nonlinear polarization rotation mirror is
      proposed for pedestal suppression of ultrashort pulses. Environmentally stable
      and precisely controllable operation is demonstrated. The main pulse and pedestal
      components are separated and picked out from the different ports. By use of the
      soliton effect and nonlinear polarization rotation, almost transform-limited
      pedestal-free 318 and 143 fs ultrashort pulses with peak powers of 0.9 and 1.7 kW
      are successfully generated. The maximum pedestal-suppression ratio is 24 dB, and
      the pick-out efficiency is up to 46% including coupling loss. The characteristics
      are analyzed both experimentally and numerically.

PMID- 18087528
TI  - Attosecond-resolution timing jitter characterization of free-running mode-locked
      lasers.
AB  - Timing jitter characterization of optical pulse trains from free-running mode
      locked lasers with attosecond resolution is demonstrated using balanced optical
      cross correlation in the timing detector and the timing delay configurations. In
      the timing detector configuration, the balanced cross correlation between two
      mode-locked lasers synchronized by a low-bandwidth phase-locked loop is used to
      measure the timing jitter spectral density outside the locking bandwidth. In
      addition, the timing delay configuration using a 325 m long timing-stabilized
      fiber link enables the characterization of timing jitter faster than the delay
      time. The limitation set by shot noise in this configuration is 2.2 x 10(-8)
      fs(2)/Hz corresponding to 470 as in 10 MHz bandwidth.

PMID- 18087529
TI  - Tissue refractometry using Hilbert phase microscopy.
AB  - We present, for the first time to our knowledge, quantitative phase images
      associated with unstained 5 mum thick tissue slices of mouse brain, spleen, and
      liver. The refractive properties of the tissue are retrieved in terms of the
      average refractive index and its spatial variation. We find that the average
      refractive index varies significantly with tissue type, such that the brain is
      characterized by the lowest value and the liver by the highest. The spatial power
      spectra of the phase images reveal power law behavior with different exponents
      for each tissue type. This approach opens a new possibility for stain-free
      characterization of tissues, where the diagnostic power is provided by the
      intrinsic refractive properties of the biological structure. We present results
      obtained for liver tissue affected by a lysosomal storage disease and show that
      our technique can quantify structural changes during this disease development.

PMID- 18087530
TI  - Fourier domain optical coherence tomography with a linear-in-wavenumber
      spectrometer.
AB  - We describe Fourier domain optical coherence tomography equipped with a novel
      linear-in-wavenumber spectrometer. The presented device linearizes the spectral
      dispersion of the spectrometer in wavenumber using a specifically designed prism.
      The spectral linearity in wavenumber makes numerical interpolation into
      wavenumber unnecessary, reduces computing time, and furthermore results in
      improvement of the falloff of signal with image range inherent to frequency
      domain optical coherence tomography imaging. Experiments demonstrate the
      improvement of the falloff and agree with the expected results from simulation.

PMID- 18087531
TI  - Double-reflection polygon mirror for high-speed optical coherence microscopy.
AB  - We report on a high-speed, high-efficiency, high-duty-cycle, path-length
      maintaining and linear beam scanner suitable for en face scanning optical
      coherence microscopy. Fast transverse beam scanning is achieved by use of a
      double-reflection polygon mirror (DRPM) rotating at a constant speed. With a
      motor speed of 18,000 rpm and a scanner diameter of 50 mm, the DRPM provides a
      line rate up to 3 kHz, +/-1.8 degrees scanning range, and 90% duty cycle. A much
      higher scanning speed and much larger scanning range can be readily achieved by
      increasing the scanner diameter.

PMID- 18087532
TI  - Devising genuine spatial correlation functions.
AB  - The choice of the mathematical form of spatial correlation functions for optical
      fields is restricted by the constraint of nonnegative definiteness. We discuss a
      sufficient condition for ensuring the satisfaction of such a constraint.

PMID- 18087533
TI  - Molecular tagging thermometry for transient temperature mapping within a water
      droplet.
AB  - We present the progress made in developing a molecular tagging thermometry (MTT)
      technique for achieving spatially and temporally resolved temperature
      measurements within a small water droplet over a solid surface. For MTT
      measurement, a pulsed laser is used to tag phosphorescent 1-BrNp.Mbeta-CD.ROH
      molecules premixed with water. Long-lived laser-induced phosphorescence is imaged
      at two successive times after the same laser excitation pulse. The temperature
      measurement is achieved by taking advantage of the temperature dependence of the
      phosphorescence lifetime, which is estimated from the intensity ratio of the
      acquired phosphorescence image pair. The measured transient temperature
      distributions can be used to quantify the unsteady heat transfer process inside
      convectively cooled water droplets over smooth or rough surfaces.

PMID- 18087534
TI  - Lighting object-based nondoped-type white organic light-emitting diode with N,N'
      diphenyl-N,N'-bis(1-naphthyl)-(1,1'-benzidine)-4,4'-diamine as the chromaticity
      tuning layer.
AB  - We demonstrate a nondoped white organic light-emitting diode in which the blue,
      green, and red emissions are generated from 4,4(')-bis(2,2(')-diphenylvinyl)
      1,1(')-biphenyl, tris(8-hydroxyquinoline)aluminum, and a submonolayer of 4
      (dicyanomethylene)-2-t-butyl-6-(1,1,7,7- tetramethyl-julolidyl 9-enyl)-4H-pyran
      layers, respectively. A thin layer of N,N(')-diphenyl-N,N(')-bis(1
      naphthyl)(1,1(')-benzidine)-4,4(')-diamine (NPB), which differed from the
      traditional hole-transporting layer, was introduced into the device. The
      thickness of this thin NPB layer was changed to tune the chromaticity and
      optimize the white color quality. The white device with a 3 nm chromaticity
      tuning NPB layer gives the Commission Internationale de l'Eclairage-1931 xy
      coordinate of (0.327, 0.336), a color rendering index of 90.2, a maximum
      luminance of 19,096 cd/m(2), and a maximum current efficiency of 4.12 cd/A. The
      electroluminescence mechanism of the white device was also discussed.

PMID- 18087535
TI  - Toward the subdiffraction focusing limit of optical superresolution.
AB  - A superresolving three-zone plate is applied to a Fresnel diffractive lens. It is
      shown that for radial incident polarization this combination produces a focal
      spot approaching superresolution allowed subdiffractive limit of 0.36lambda/NA
      for focusing. For media responsive to longitudinal field component only, our
      phase engineering scheme results in a focal spot size of 0.368lambda/NA. When
      used with a solid immersion lens, the scheme can generate the smallest focal spot
      available for passive optics.

PMID- 18087536
TI  - Integral transformation solution of free-space cylindrical vector beams and
      prediction of modified Bessel-Gaussian vector beams.
AB  - A unified description of free-space cylindrical vector beams is presented that is
      an integral transformation solution to the vector Helmholtz equation and the
      transversality condition. In the paraxial condition, this solution not only
      includes the known J(1) Bessel-Gaussian vector beam and the axisymmetric Laguerre
      Gaussian vector beam that were obtained by solving the paraxial wave equations
      but also predicts two kinds of vector beam, called a modified Bessel-Gaussian
      vector beam.

PMID- 18087537
TI  - Virtual Gires-Tournois etalons realized with phase-modulated wideband chirped
      fiber gratings.
AB  - We propose and demonstrate novel virtual Gires-Tournois (GT) etalons based on
      fiber gratings. By introducing an additional phase modulation in wideband
      linearly chirped fiber Bragg gratings, we have successfully generated GT
      resonance with only one grating. This technique can simplify the fabrication
      procedure while retaining the normal advantages of distributed etalons, including
      their full compatibility with optical fiber, low insertion loss, and low cost.
      Such etalons can be used as dispersion compensation devices in optical
      transmission systems.

PMID- 18087538
TI  - Generation of arbitrary vector beams with a spatial light modulator and a common
      path interferometric arrangement.
AB  - We describe a convenient approach for generating arbitrary vector beams in a 4-f
      system with a spatial light modulator (SLM) and a common path interferometric
      arrangement. A computer-generated hologram is introduced onto SLM for performing
      the beam conversion. Optical realization of a variety of polarization
      configurations confirms the reliability and flexibility of our method.

PMID- 18087539
TI  - Finding electromagnetic and chemical enhancement factors of surface-enhanced
      Raman scattering.
AB  - The authors report two methods to determine electromagnetic and chemical
      enhancement factors in surface-enhanced Raman scattering (SERS), which are based
      on saturation property and decay dynamics of photoluminescence and concurrent
      measurements of photoluminescence and resonance Raman scattering intensities.
      Considerations for experimental implementation are discussed. This study is
      expected to facilitate the understanding of SERS mechanisms and the advancement
      of the usage of SERS in chemical and biological sensor applications.

PMID- 18087540
TI  - Femtosecond fluorescence upconversion setup with broadband detection in the
      ultraviolet.
AB  - We show a femtosecond fluorescence upconversion setup with broadband detection to
      measure time-resolved emission spectra in the 300-550 nm range, upon excitation
      between 250 and 300 nm, with a time resolution of 100 fs. We present time
      resolved fluorescence emission spectra of 2,5-diphenyloxazole in solution, which
      demonstrate the capabilities of the setup.

PMID- 18087541
TI  - Amplitude ambiguities in second-harmonic generation frequency-resolved optical
      gating.
AB  - We construct field shapes with distinct amplitude profiles that have nearly
      identical second-harmonic generation frequency-resolved optical gating (SHG FROG)
      traces. Although such fields are not true mathematical ambiguities, they result
      in experimentally indistinguishable FROG traces. These fields are neither time
      reversed copies nor pulselets with a mere relative phase difference, which are
      well known nontrivial ambiguities for SHG FROG. We also show that for certain
      example fields, second-order interferometric autocorrelation is more sensitive to
      the pulse shape than is SHG FROG.

PMID- 18087542
TI  - [Effect of hydrogen sulfide on oxidative stress in hypoxic pulmonary
      hypertension].
AB  - OBJECTIVE: To study the modulatory effect of hydrogen sulfide (H(2)S) on
      oxidative stress in the development of pulmonary hypertension induced by hypoxia.
      METHODS: Twenty male Wistar rats were randomly divided into control group (n=6),
      hypoxic group (n=6) and hypoxia+NaHS group (n=8). Hypoxic challenge was performed
      everyday for 21 days. NaHS solution was injected intra-peritoneally everyday
      before hypoxic challenge for rats in the hypoxia+NaHS group. After 21 days of
      hypoxia, the mean pulmonary artery pressure(mPAP) was measured by cardiac
      catheterization. The weight ratio of right ventricle to left ventricle+septum
      [RV/(LV+SP)] was also measured. The lung homogenates were assayed for total
      antioxidant capacity(T-AOC), superoxide dismutase (SOD), oxidized glutathione
      (GSSG), reduced glutathione (GSH), malondialdehyde(MDA) and hydroxy radical(*OH),
      and the SOD mRNA levels were assayed by real time polymerase chain reaction.
      RESULTS: After three weeks of hypoxic disposure, hypoxic hypertension and
      vascular remodeling developed. Compared with the control group, the mPAP[(23.7+/
      2.2) mm Hg vs (16.3+/-3.7) mm Hg,P<0.01] and the weight ratio of RV/(LV+SP)
      increased (P<0.01), but lung tissue T-AOC was decreased by 21.4% (P<0.01).But
      GSSG was increased by 68.5% (P<0.01) as compared with those of the control rats.
      However, compared with those of the hypoxic group, the mPAP in rats of
      hypoxia+NaHS group was decreased [(16.3+/-2.8) mm Hg vs (23.7 +/-2.2) mm Hg].
      Administration of NaHS increased T-AOC by 18.8% (P<0.05) but eliminated GSSG by
      23.2% (P<0.05) in rats of hypoxia+NaHS group as compared with the hypoxic group.
      There were no significant changes in lung tissue SOD mRNA level and its capacity
      among the three groups. CONCLUSION: Hydrogen sulfide acted as antioxidant during
      the oxidative stress of hypoxic pulmonary hypertension, and the mechanism was
      partly through attenuating the content of GSSG.

PMID- 18087543
TI  - [Different expressions of inflammatory cytokines in two types of cardiac
      hypertrophy in rats].
AB  - OBJECTIVE: To compare the different expressions of cardiac inflammatory cytokines
      including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta(IL-1beta),
      interleukin-6 (IL-6) in two types of cardiac hypertrophy rat models induced by
      volume overload and pressure overload. METHODS: Volume overload-induced cardiac
      hypertrophy was established by abdominal arteriovenous fistula (ACF) and pressure
      overload-induced cardiac hypertrophy was developed by constriction of aorta (CA).
      Heart weight measurement and histological examination were performed 1 week or 2
      weeks after the operation respectively. The cytokine expression was measured by
      enzyme linked immunosorbent assay. RESULTS: All the operated groups developed
      cardiac hypertrophy. The left ventricular fractional shortening of each operated
      group had no significant difference with the sham-operated groups respectively.
      As far as the total amount of each cytokine in left ventricular myocardium was
      concerned, compared to the sham-operated groups, IL-6 and IL-1beta both increased
      significantly in CA groups [IL-6(23 722+/-8 671)pg vs (17 693+/-5 705)pg,P<0.05
      ;IL-1beta(335+/-95)pg vs (159+/-99) pg,P<0.01].There was no difference of TNF
      alpha between operated and sham-operated groups in ACF or CA groups . CONCLUSION:
      The contents of IL-6 and IL-1beta in myocardium increased in pressure overload
      induced cardiac hypertrophy.

PMID- 18087544
TI  - [Study on polymorphism in the apolipoprotein A5 gene in patients with premature
      coronary heart disease].
AB  - OBJECTIVE: To investigate the association between the apolipoprotein A5(APOA5) 
      1131T/C polymorphism and premature coronary heart disease in northern Chinese Han
      population. METHODS: Using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) and polyacrylamide gel electrophoresis (PAGE), we
      analyzed the genotype and allele distribution in 140 patients with premature
      coronary heart disease diagnosed by coronary angiography and 156 healthy
      controls. The levels of serum lipid profiles were also studied by biochemical
      methods. RESULTS: The allele frequency of APOA5-1131T/C polymorphism in the
      premature coronary heart disease group was significantly higher (43.2% vs. 33.0%,
      P=0.011) than that in the control group. Compared with TT homozygotes, CC
      homozygotes exhibited a 2.809-fold (95% CI 1.331-5.927) increased risk of
      developing premature coronary heart disease. Logistic regression analysis found
      that this correlation was independent of sex, age, body mass index (BMI), smoking
      history as well as serum total cholesterol(TC), high density lipoprotein
      cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels; In
      premature coronary heart disease group, the triglyceride(TG) level in CC
      homozygotes was significantly higher than those in TC heterozygotes or TT
      homozygotes. CONCLUSION: The APOA5-1131T/C polymorphism has influence on serum TG
      level, and the APOA5-1131C allele is associated with the development of premature
      coronary heart disease in northern Chinese Han population.

PMID- 18087545
TI  - [Isoproterenol regulates lipopolysaccharide-induced tumor necrosis factor-alpha
      and interleukin-6 production in monocytes from essential hypertensive patients.].
AB  - OBJECTIVE: To investigate the effects of beta-adrenoceptor agonist
      isoproterenol(ISO) on lipopolysaccharide(LPS) induced inflammatory cytokine-tumor
      necrosis factor-alpha(TNF-alpha) and interleukin-6(IL-6)] in monocytes from
      essential hypertensive patients (Stage I). METHODS: Monocytes were isolated from
      17 healthy volunteers and 6 hypertensive patients' venus blood, and the monocytes
      were cultured with LPS (0.2 microg/L) and ISO. The concentrations of TNF-alpha
      and IL-6 in the cultured supernatant were measured with enzyme-linked
      immunosorbent assays. RESULTS: (1) TNF-alpha production induced by LPS in
      monocytes from hypertensive group were higher than those from control group
      [(1,897+/-393) ng/L vs. (975+/-473) ng/L, P<0.01]. But the differences of IL-6
      production were not significant between the two groups [(5,532+/-796) ng/L vs.
      (6,092+/-2 249) ng/L, P>0.05]. (2) ISO inhibited extracellular TNF-alpha
      production induced by LPS in a dose-dependent manner. The inhibitory effects were
      ameliorated by beta-adrenoceptor antagonist propranolol. In contrast, ISO had no
      effect on the production of IL-6 induced by LPS. The difference of inhibitory
      effects of ISO on TNF-alpha production was not statistically significant between
      hypertensive group and healthy control group (P>0.05). CONCLUSION: beta
      adrenergic activation inhibits TNF-alpha (but not IL-6) production induced by LPS
      in monocytes. The inhibitory effects were not different between early staged
      hypertensive patients and healthy subjects.

PMID- 18087546
TI  - [Association of microalbuminuria and von Willebrand factor with metabolic
      syndrome in hypertensive patients].
AB  - OBJECTIVE: To compare the difference of microalbuminuria (MAU) and von Willebrand
      factor (vWF) between essential hypertensives and hypertensive patients with
      metabolic syndrome (MS), and to explore the association of these factors with MS.
      METHODS: According to the new definition of MS by International Diabetes
      Federation (IDF) for 2005, 133 consecutive essential hypertensives were divided
      into two groups: hypertensive patients with metabolic syndrome (EH-MS group,
      n=97), and essential hypertensives (EH group, n=36). Biochemistry assay, plasma
      vWF, 24 hours urine albumin excretion (UAE) and morning urine albumin/creatinine
      ratio (ACR) were measured. The association of MAU and vWF with MS was analysed.
      RESULTS: Waist circumference, body mass index, triglyceride (TG), low density
      lipoprotein cholesterol (LDL-C), plasma vWF and UAE were increased(P<0.05 or
      P<0.01, respectively), while high density lipoprotein cholesterol (HDL-C) was
      decreased (P<0.01) in EH-MS group, as compared with those in EH group. UAE was
      positively correlated with ACR (r=0.707, P<0.01). vWF was not correlated with UAE
      or ACR (r=0.079 and 0.052,P>0.05, respectively). Logistic regression showed HDL
      C, TG, LDL-C,vWF and UAE were associated with the development of MS in
      hypertensive patients (standardized coefficients: -0.825, 0.63, 0.339, 0.331,
      0.371,P<0.05 or P<0.01, respectively). CONCLUSION: Compared with essential
      hypertensives, the hypertensive patients with MS had more MAU and serious
      endothelial dysfunction. UAE was correlated significantly with ACR. vWF and UAE
      were associated with the development of MS in patients with hypertension.

PMID- 18087547
TI  - [Screening for dyslipidemia based on family history combined with obesity in
      children].
AB  - OBJECTIVE: To explore the significance of family history combined with obesity in
      screening dyslipidemia in children. METHODS: Cluster-randomized samplings in a
      transecting epidemiological survey for children aged 6 to 18 years in Beijing
      area were used. A total of 9,495 boys and 9,542 girls were virtually included in
      the study. They were divided into four groups as school boys, adolescent boys,
      school girls and adolescent girls. Their fasting capillary blood total
      cholesterol (TC) levels, triglyceride (TG) levels, body height and body weight
      were detected. RESULTS: Of the detected children, 38% were with family history,
      4.9% obese, 2.5% both obese and positive family history and 40.4% with positive
      family history or obese. The percentages of dyslipidemia in non-obese children
      without family history, non-obese children with family history, obese children
      without family history, and obese children with family history were as follows:
      hyperlipidemia: 7.9%, 9.6%, 30.1% and 31.5%, respectively; hypercholesterolemia:
      0.9%, 1.5%, 3.3% and 2.9%, respectively; hypertriglyceridemia: 7.1%, 8.6%, 29.2%
      and 31.3% respectively. Odds Ratios (95%CI) of dyslipidemia in obese children
      including school boys, adolescent boys, school girls and adolescent girls were
      6.439(4.178-9.925),6.287 (4.153-9.518),5.063 (3.041-8.427) and 3.665 (2.536
      5.296),respectively. Odds Ratios (95%CI) of dyslipidemia in children with family
      history including school boys, adolescent boys, school girls and adolescent girls
      were 1.204 (0.952-1.522) (P=0.121),1.331 (1.047-1.692) (P=0.020),1.095 (0.847
      1.416) (P=0.490) and 1.260 (1.070-1.483) (P=0.005), respectively. In children
      with dyslipidemia, 43.8% were with positive family history, 15.8% obese, 8.2%
      both obese and positive family history, and 51.3% either obese or positive family
      history. CONCLUSION: Family history combined with obesity is important in
      identifying dyslipidemia in children.

PMID- 18087548
TI  - [Correlation between Duke treadmill score and corrected thrombolysis in
      myocardial infarction frame count in patients with coronary atherosclerotic heart
      disease].
AB  - OBJECTIVE: To investigate the correlation between Duke treadmill score (DTS) and
      corrected thrombolysis in myocardial infarction frame count(CTFC )in patients
      with coronary atherosclerotic heart disease(CAD). METHODS: Seventy-two patients
      with coronary atherosclerotic heart disease, who underwent treadmill exercise
      tests in 2 weeks before coronary angiography were enrolled in our study. All the
      patients were divided into 2 groups according to the value of DTS: low-risk group
      (DTS > or = 5) and moderate-high-risk group (DTS < 5). We evaluated the
      correlation between DTS and CTFC and compared the differences between the two
      groups. RESULTS: DTS had a negative correlation with CTFC of left anterior
      descending branch (LAD), left circumflex artery (LCX) and right coronary artery
      (RCA)(r = -0.821,-0.730,-0.598, P<0.001). CTFC of all coronary arteries in the
      low-risk group was much lower than that of moderate-high-risk group [LAD:
      (22.27+/-3.71) frames vs (24.12+/-4.19) frames, respectively; LCX: (27.96+/-5.65)
      frames vs (31.28+/- 6.79) frames, respectively; RCA: (21.96+/-5.85) frames vs
      (24.64+/-7.33) frames, respectively], there was significant difference between
      the two groups. CONCLUSION: There was a negative correlation between DTS and CTFC
      of left anterior descending branch, left circumflex artery and right coronary
      artery in patients with CAD. The risk stratification on the basis of DTS had a
      notable association with CTFC. These results may provide a theoretical evidence
      for utilizing the non-invasive method DTS to evaluate prognosis of patients with
      CAD.

PMID- 18087549
TI  - [Association between plasma adiponectin levels and coronary lesion complexity].
AB  - OBJECTIVE: To explore the association between the levels of plasma adiponectin
      and coronary artery lesion complexity in patients undergoing coronary
      angiography. METHODS: We measured the plasma concentrations of adiponectin in 105
      candidates [28 healthy controls and 77 patients with coronary artery diseases
      (CAD)]. The complexity of coronary artery lesion was evaluated by the numbers of
      vessel disease and Gensini score. RESULTS: Plasma concentrations of adiponectin
      in healthy group were significantly higher than those in CAD patients. Among
      patients with CAD, those with multiple vessel lesions had significantly lower
      adiponectin levels than those with a single vessel lesion. Plasma concentrations
      of adiponectin in Gensini score > or = 30 group were significantly lower than
      those in <30 group and control group(P<0.05). Patients with acute coronary
      syndrome (ACS) had lower adiponectin levels than those without ACS [(0.731+/
      0.361) mg/L vs. (1.097+/-0.617) mg/L,P=0.03]. Logistic analysis indicated that
      the lower level of adiponectin was independent risk factor of coronary stenosis
      (OR 0.214, 95% CI 0.071-0.646, P=0.006) and unstable plaque (OR 0.151, 95% CI
      0.044-0.515, P= 0.003). Adiponectin concentrations were correlated positively
      with high density lipoprotein cholesterol(HDL-C) and negatively with C-reactive
      protein and triglyceride(TG). CONCLUSION: The decreased plasma adiponectin
      concentration might be associated with the coronary artery lesion and be used as
      an independent predictor of the occurrence and severity of coronary
      atherosclerosis and the stability of plaque.

PMID- 18087551
TI  - [Value of left ventricular ejection fraction in coronary artery bypass grafting
      patients].
AB  - OBJECTIVE: To evaluate the role of the left ventricular ejection fraction (LVEF)
      in coronary artery bypass grafting(CABG)patients. METHODS: From 2004 to 2005,215
      patients underwent CABG and there were 36 cases with LVEF<0.40(low LVEF group)
      whereas 179 cases with LVEF>0.40(normal LVEF group). Correlative data of the two
      groups were compared and analyzed statistically. RESULTS: Compared with the
      normal EF group, the EuroSCORE of the low EF group was much higher (mean 6.4+/
      1.7) and many more patients of the low EF group had concomitant moderate to
      severe mitral valve insufficiency and aneurysm that needed simultaneous surgical
      operation(55.6%).Two patients died in hospital(5.5%)in the low EF group whereas
      five patients in the normal EF group(2.8%, P<0.05).In the low EF group,34
      survivors(94.5%)were free of angina. Low cardiac output was the main
      postoperative complication. The mean EF was significantly improved
      postoperatively (mean 0.47+/-0.11)(P<0.05). CONCLUSION: EF<0.40 is indeed a risk
      factor for patients with coronary artery disease. Most of them have concomitant
      moderate to severe mitral valve insufficiency and aneurysm that need simultaneous
      surgical operations. The early surgical result of them is of satisfaction.

PMID- 18087550
TI  - [Investigation and screening of glucose metabolism in essential hypertension
      patients without diagnosed diabetes mellitus].
AB  - OBJECTIVE: To obtain the glucose metabolic profile of patients with essential
      hypertension in China. METHODS: This is an epidemiologic cross-sectional survey
      and screening study, 5 sites in China participated in. Patients with essential
      hypertension and without known diabetes mellitus(DM) answered the questionnaire
      and received in-site fasting blood glucose (FBG) determination and simple oral
      glucose tolerance test (OGTT). RESULTS: A total of 1,421 patients had the data of
      FBG and OGTT 2-hour glucose. Among them, The prevalence rates of newly diagnosed
      DM and impaired glucose regulation (IGR) were 22.9% and 64.4% respectively.
      Patients with newly diagnosed DM have higher systolic blood pressure, waistline,
      waist-to-hip ratio and plasma triglyceride. CONCLUSION: Newly diagnosed disturbed
      glucose metabolic status is common among patients with essential hypertension
      without DM history, which had very low diagnose rate in routine work. We must pay
      more attention to the glucose metabolic status of patients with hypertension,
      especially the one with metabolic syndrome, OGTT should be as a routine procedure
      in the diagnosis of such patients.

PMID- 18087552
TI  - [Effects of Verapamil and Metoprolol on heart rate variability in patients with
      coronary heart disease].
AB  - OBJECTIVE: To evaluate the effects of Verapamil and Metoprolol on improving heart
      rate variability(HRV) in patients with coronary heart disease (CHD). METHODS: A
      total of 60 patients, who were diagnosed as CHD according to the results of
      coronary angiography, were enrolled. All patients were randomly divided into
      Verapamil group (n=30) and Metoprolol group (n=30). The patients in Verapamil
      group received Verapamil (480 mg/d) and the patients in Metoprolol group received
      Metoprolol (50 mg/d) for eight weeks. Office blood pressure, HRV, symptoms of
      angina Holter recording heart rates per minute and HRV for eight weeks were
      observed before and after treatment in both groups. RESULTS: Both office blood
      pressures and the numbers of attacks of angina pectoris and symptoms all
      decreased obviously in the two groups after treatment. Blood pressures were
      reduced from 137.12/84.36 mm Hg to 131.80/77.68 mm Hg in Metoprolol group, and
      also reduced from 137.72/83.92 mm Hg to 129.56/78.76 mm Hg in Verapamil group
      (P>0.05, compared between the two groups). In both the Verapamil and Metoprolol
      groups, heart rates decreased, SDNN (standard deviation of all normal to normal
      RR intervals) and HRVTI (HRV indexes of time-domain) both increased significantly
      after treatment (P>0.05). And HRV indexes of low-frequency(LF), high-frequency
      (HF) and total power (TP) were increased obviously, while the low-to high
      frequency ratio (LF/HF), very-low-frequency (VLF) were remarkably lower(P<0.05).
      Compared with Verapamil group, the changes of frequency-domain indexes in
      Metoprolol group were significant(P<0.05). CONCLUSION: In patients with CHD, both
      Metoprolol and Verapamil can increase the HRV.

PMID- 18087553
TI  - [Efficacy and safety of Enalapril-Folate acid tablets in lowering blood pressure
      and plasma homocysteine].
AB  - OBJECTIVE: To investigate the efficacy and safety of Enalapril-Folic acid tablets
      in lowering blood pressure and plasma homocysteine(Hcy) level. METHODS: A
      randomized, double blind, multicenter clinical trial was performed. Subjects with
      mild-moderate hypertension were randomly assigned to the following three groups:
      group 1, Enalapril 10.0 mg/d; group 2, Enalapril 10.0 mg+ Folic acid 0.4 mg/d;
      group 3, Enalapril 10.0 mg + Folic acid 0.8 mg/d. Blood pressure and plasma Hcy
      level were examined every two weeks, for a total period of 8 weeks. RESULTS: A
      total of 480 hypertensives were enrolled. All analyses were performed according
      to the intention to treat and included all randomized patients. Compared to group
      1, both group 2 and group 3 had significantly higher effectiveness in lowering
      both blood pressure and plasma Hcy level, or in lowering either blood pressure or
      plasma Hcy level. The proportions of subjects showing obvious reduction in both
      blood pressure and plasma homocysteine level in group 1, group 2, group 3, were
      4.6%, 13.2%, 17.1%, respectively; the proportions of subjects showing obvious
      reduction in either blood pressure or plasma homocysteine level in group 1, group
      2, group 3, were 45.8%, 59.6%, and 65.1%, respectively; Effects on blood
      pressure, as well as the safety profile were not significantly different among
      the three regimens. CONCLUSION: Enalapril-Folic acid tablets could be used to
      reduce both blood pressure and plasma Hcy level in mild to moderate hypertensive
      subjects.

PMID- 18087554
TI  - [Efficacy, safety and tolerance of Felodipine controlled release tablets and
      Felodipine controlled release tablets associated combination therapy in the
      treatment of mild to moderate essential hypertension in China].
AB  - OBJECTIVE: To evaluate the efficacy, safety and tolerance of Felodipine
      controlled release tablets and Felodipine controlled release tablets associated
      combination each with Metoprolol, Lisinopril or Hydrochlorothiazide in the 12
      weeks treatment of mild to moderate essential hypertension in China. METHODS:
      Multicenter, random samples, and open study have been processed. RESULTS:
      (1)After 12 weeks associated combination treatment of anti-hypertension, the
      percentages of the persons who had attained the target were 80.2% of ITT group in
      Felodipine controlled release tablets associated combination with
      Hydrochlorothiazide, 74.1% of ITT group in with Metoprolol,and 80.5% of ITT group
      in with Lisinopril, respectively. (2)Mean reductions of systolic/diastolic blood
      pressure from baseline were 16.8/10.6 mm Hg in combination with
      Hydrochlorothiazide, 16.6/10.7 mm Hg in combination with Metoprolol,and 18.0/12.8
      mm Hg in combination with Lisinopril each. There was no significant difference
      among these three groups (P>0.05). With the Felodipine controlled release tablets
      treatment alone, the mean reductions from baseline was 24.8/17.5 mm Hg. But in
      combination with Lisinopril, the blood pressure could lower more quickly, and
      then could reach the target more rapidly. (3)In the ITT group, the drug
      compliance with Felodipine controlled release tablets was 97.7%, with those in
      combination with Hydrochlorothiazide 89.8%, with those in combination with
      Metoprolol 100.0%, and with those in combination with Lisinopril 96.4%. The main
      adverse event related to Felodipine was headache, and to Lisinopril was cough.
      CONCLUSION: Antihypertensive drug Felodipine controlled release tablets are good
      and effective. And Felodipine controlled release tablet associated combination
      each with Metoprolol, Lisinopril or Hydrochlorothiazide can make most patients
      reach the treatment target, with safety, good tolerance, and high compliance.

PMID- 18087555
TI  - [Renal insufficiency and clinical outcomes in patients with acute coronary
      syndrome undergoing percutaneous coronary intervention: a multi-centre study].
AB  - OBJECTIVE: To investigate the association of renal insufficiency and clinical
      outcomes in patients with acute coronary syndrome(ACS). METHODS: The study was a
      multi-centre register study including 3,589 ACS patients coming from 39 centers
      across China who had received percutaneous coronary intervention(PCI) prior to
      1st February, 2007. Estimated glomerular filtration rate (eGFR) was calculated
      for all patients using the 4-variable MDRD equation with the serum creatinine
      obtained before angiography. The association between renal insufficiency and
      clinical outcomes and the presence of in-hospital death and bleeding was studied
      by Fisher's exact test. Multi-variable analysis on the risk factors of in
      hospital bleeding was done by logistic regression test. RESULTS: The mean age of
      the study population was (61.74+/-11.37) years (ranging from 23 years to 92
      years)and 76.5% (2,746/3,589) of the population was male. Only 90 patients
      (2.51%) were known to have chronic kidney disease at the time of admission and
      144 patients(4.01%) had serum creatinine levels above 133 micromol/L. However,
      after the evaluation of renal status by the MDRD equation, 2,250 patients
      (63.1%)showed a reduction in eGFR of less than 90 mL/min, of whom, 472 (13.1%)
      even reached the level of moderate renal insufficiency (eGFR<60 mL/min) and
      above. Seven patients(0.20%) were proved to have chronic total occlusion
      lesions(CTO) and eight (0.22%) needed shift to coronary artery bypass grafting
      (CABG) after angiography. Both the presence of CTO lesions and CABG were proved
      to be associated with decrease of renal function through Fisher's exact test (P=
      0.005 8 and 0.041, respectively). The in-hospital mortality rate was 0.47%(17/3
      589) which was associated with the degree of renal insufficiency (P=0.001 3). A
      total of 75 patients(2.09%) of in-hospital bleeding were recorded with 26
      patients(0.72%) diagnosed as major bleeding events. 92% (69/75) of the bleeding
      events occurred after PCI. Bleeding was found to be associated with the degree of
      renal insufficiency in every type of antithrombotic therapy (P<0.001). After
      adjusting with other variables by logistic regression test, renal insufficiency
      (eGFR per 10 mL/min decrease, OR=1.133, 95% CI 1.011- 1.27, P=0.032)and age
      (above 65 years, OR=1.907, 95% CI 1.107-3.28, P=0.02) were proved to be the risk
      factors of in-hospital bleeding. CONCLUSION: Renal insufficiency is very common
      in ACS patients but self-report rate is low among this population. Renal function
      evaluated by eGFR should be carried out for every patient hospitalized for ACS
      for risk stratification. Patients with severer renal insufficiency usually have
      more complicated clinical manifestations and a higher rate of in-hospital
      bleeding.

PMID- 18087556
TI  - [Impact of normal flow (TIMI-3) before coronary intervention therapy on the
      survival of patients suffering acute myocardial infarction].
AB  - OBJECTIVE: To define impact of spontaneous TIMI-3 flow before angioplasty on
      outcomes of percutaneous coronary intervention strategy and the prognosis in
      patients with acute myocardial infarction (AMI). METHODS: The consecutive 301
      patients enrolled in the ongoing register of emergent coronary angioplasty within
      12 hours from symptoms who were diagnosed as having ST elevation AMI in our
      hospital from 2000 to 2006 were analyzed, they were followed up for one year and
      the clinical characteristics and survival rates were analysed. RESULTS: Among the
      301 patients enrolled in the ongoing register of emergent coronary angioplasty,
      spontaneous reperfusion (TIMI-3 flow) was present in 14.6% at initial
      angiography. Compared with patients without TIMI-3 flow, those with TIMI-3 flow
      before coronary intervention were less likely to present in new-onset heart
      failure(2.3% versus 16%, P=0.016), Patients with initial TIMI-3 flow had
      significantly lower 30-day mortality (0% versus 9.3%, P=0.035) , and cardiogenic
      shock (0%versus 8.6%, P=0.044) and had a shorter hospital stay (P=0.008).
      Cumulative 1-year mortality was 0% in patients with initial TIMI-3 flow, 11.3%
      with TIMI 0-2 flow (P=0.019). By COX regression analysis, post procedural TIMI-3
      flow was an independent determinant of survival (OR=0.285,P=0.004) , however,TIMI
      3 flow before coronary intervention was not found as an independent determinant
      of survival significantly. The lenitive symptoms and current smoking were the
      independent determinants of TIMI-3 flow before coronary intervention (P=0.005,
      P=0.048, respectively). CONCLUSION: Patients undergoing primary percutaneous
      transluminal coronary intervention in whom TIMI-3 flow is present before
      angioplasty may present with greater clinical and angiographic evidence of
      myocardial salvage, be less likely to develop complications related to left
      ventricular failure, and improve early and late survival.

PMID- 18087557
TI  - [Intracoronary transfer autologous bone marrow stem cells can improve cardiac
      function in patients with left ventricular dysfunction after myocardial
      infarction].
AB  - OBJECTIVE: To evaluate the efficacy of intracoronary transfer of autologous bone
      marrow mononuclear stem cells in patients with heart dysfunction after myocardial
      infarction. METHODS: Forty-two patients with anterior myocardial infarction
      [BMSC(bone marrow mononuclear stem cells) group: 13 cases; control group: 29
      cases] were treated by standard percutaneous coronary intervention (PCI) and
      medical therapy. Patients in BMSC group were also transplanted bone marrow
      mononuclear stem cells through coronary injection. Baseline and 12 months' follow
      up evaluations included New York Heart Association Class ( NYHA class) and the
      level of plasma NT-proBNP, six minutes walk test, single photon emission computed
      tomography(SPECT). RESULTS: In BMSC group, the NYHA class improved significantly
      at the end of the 12 months' follow-up (1.54+/-0.27 vs. 2.62+/-0.33, P=0.002) and
      was better than that of control group (2.45+/-0.21, P=0.02). The level of plasma
      NTjproBNP reduced significantly [(701.05+/-154.60) ng/L vs. (1,921.70+/-373.70)
      ng/L, P=0.000 8]. The distances of six minutes walk test of the two groups
      increased significantly [BMSC group: (432.85+/-27.81) m vs. (363.77+/-20.14) m,
      P=0.000 6;control group: (381.48+/-17.72) m vs. (339.00+/-9.87) m, P=0.000 5],
      but the difference was not obvious between the two groups. The score of
      myocardial blood perfusion improved significantly in BMSC group at the end of the
      12 months' follow-up (31.15+/-3.65 vs. 46.31+/-2.87, P=0.002) and was better than
      that of control group (42.59+/-2.08,P=0.015 7). The area of the perfusion defects
      in SPECT reduced significantly in BMSC group [(32.23+/-4.40)% vs. (39.54+/
      3.76)%, P=0.000 1], but no obvious difference was found between the two groups.
      Global LVEF of BMSC group increased [(38.54+/-2.94)% vs. (35.38+/-2.16)%,
      P>0.05). CONCLUSION: Intracoronary transplantation of bone marrow mononuclear
      cells could improve myocardial blood perfusion and increase the systolic function
      in patients with heart failure after myocardial infarction.

PMID- 18087558
TI  - [Clinical living donor liver transplantation: a report of 4 cases].
AB  - OBJECTIVE: To investigate principal surgical techniques of living donor liver
      transplantation (LDLT) . METHODS: A retrospective analysis was made in 4 cases
      undergoing living donor liver transplantation from Feb. 2003 to Nov. 2006.
      RESULTS: All the living donors of 4 cases were adults, including the right lobe
      transplanted in 3 patients (not including the middle hepatic vein in 2, including
      the middle hepatic vein in one), the extended left lateral lobe (not including
      the middle hepatic vein) in one. The graft-to-recipient weight ratio (GRWR) was
      0.85%-1.44%. The right hepatic vein reconstructions were performed in end to end
      anastomoses in 3 patients. The left and middle hepatic vein reconstruction was
      performed in end to end left hepatic vein of graft anastomosis in one. The
      arterial anastomoses were performed in end to end, including the right hepatic
      arteria of the graft to the hepatic proprial arteria in 2 patients, the branch of
      the right hepatic arteria of the graft through the radialis arteria to the
      hepatic proprial arteria in one, the left hepatic arteria of the graft to the
      hepatic proprial arteria in one. Biliary reconstructions were made by using duct
      to duct anastomoses, and placement of a T tube in 2 patients. All 4 donors were
      uneventfully discharged after operation. Four recipients were without vascular
      complication, and the stoma of bile duct was light stegnosis in a child recipient
      without "T" tube. They have been surviving 58 months, 32 months, 20 months and 14
      months respectively. CONCLUSION: The process of LDLT was complicated, and the
      surgical technique was difficult. Choosing suitable donors and flexible mastering
      of the principal surgical techniques can achieve favorable prognosis of LDLT.

PMID- 18087559
TI  - [Clinical and echocardiographic features of constrictive pericarditis: analysis
      of 36 cases with literature review].
AB  - OBJECTIVE: To analyze the clinical and echocardiographic features of constrictive
      pericarditis. METHODS: Thirty-six patients diagnosed as having constrictive
      pericarditis from Oct. 1989 to Jun. 2007 were enrolled in this retrospective
      study. Clinical manifestations and echocardiographic features were analyzed.
      RESULTS: The main clinical manifestations were fatigue, effort dyspnea(100%), and
      sign of pressure elevation of vena cava(97%). Echocardiographic features included
      thickening of pericardium(67%), abnormal motion of septal and posterior wall of
      left ventricle in diastole(83%, 75% respectively), left and right atrial
      enlargement(92%,39% respectively), early filling changes of mitral flow with
      respiration(93%), inferior vena cava dilation and without respiration
      variation(100%), mitral annulus paradoxical enhanced motion in early diastole.
      CONCLUSION: Clinical manifestations of pressure elevation of vena cava were
      indicators for diagnosis of constrictive pericarditis. Echocardiography could be
      a valuable method for confirming the diagnosis.

PMID- 18087560
TI  - [Diagnostic performance of 64-channel multislice computed tomography in
      assessment of significant coronary artery disease in subjects suspected as acute
      coronary syndrome and stable angina.].
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of 64-channel multislice spiral
      computed tomography (MSCT) in subjects with presentations suggestive of stable
      angina or acute coronary syndrome. METHODS: Subjects received both 64-channel
      MSCT and coronary angiography, from Feb. 2006 to Feb. 2007, were enrolled for
      retrospective analyses. Results of the quantitative coronary angiography were
      used as the "Golden criteria", accuracy of 64-channel MSCT were evaluated in the
      overall sample, as well as in subjects suspected of stable angina and acute
      coronary syndrome. RESULTS: A total of 120 subjects were enrolled in the
      analyses. On the patient level, the sensitivity, specificity, and accuracy of 64
      channel MSCT in detecting significant stenoses were 92.5%, 50%, and 87.5%,
      respectively. The overall ROC area under curve was 0.71. On the artery level,
      sensitivity, specificity, positive predictive value, negative predictive value,
      and ROC area under curve of 64-channel MSCT were 69.9%, 83.8%, 81.1%, 73.7%, and
      0.77, respectively. Further analyses showed the sensitivity, specificity,
      positive predictive value, negative predictive value, and ROC area under curve of
      64-channel MSCT in subjects presenting as stable angina and in subjects
      presenting as acute coronary syndrome were as follows: 70.2% vs 69.2%, 76.2% vs
      86.0%, 74.7% vs 85.6%, 71.9% vs 69.9%, and 0.73 vs 0.78. CONCLUSION: The accuracy
      rates of 64-channel MSCT in subjects presenting as stable angina and in subjects
      presenting as acute coronary syndrome were similar.

PMID- 18087562
TI  - [Effect of Ganoderma lucidum polysaccharides peptide on invasion of human lung
      carcinoma cells in vitro].
AB  - OBJECTIVE: To find out the effects of Ganoderma lucidum polysaccharides peptide
      (Gl-PP) on the invasion of the human lung carcinoma cell (PG cell). METHODS: PG
      cells were pretreated with different concentration Gl-PP in vitro, using cell
      proliferation assay, cell migration assay, adhesion assay, zymography and RT-PCR,
      then the effects of Gl-PP on proliferation, motility, adhesion and MMP-9 activity
      and mRNA expression of PG cells were investigated in vitro. RESULTS: Gl-PP did
      not directly inhibit PG cell proliferation in vitro. However, pretreated with Gl
      PP, PG cells motility was inhibited significantly. PG cells adhesion was also
      inhibited. The activity of MMP-9 was inhibited in a dose-dependent manner, and
      the inhibited ratio was 41.53% at a dose of 100 mg/L Gl-PP. The mRNA expression
      of MMP-9 of pretreated PG cells was inhibited. CONCLUSION: Gl-PP could suppress
      invasion of human lung carcinoma cells in vitro.

PMID- 18087561
TI  - [Long-term intensive glycemic and lipid control ameliorates the carotid intima
      medial thickness in type 2 diabetes mellitus].
AB  - OBJECTIVE: To investigate whether long-term intensive glycemic and lipid control
      would ameliorate the carotid intima medial thickness (IMT) in patients with type
      2 diabetes mellitus (T2DM). METHODS: IMT was evaluated on B-mode ultrasonography
      in 116 patients with T2DM. Body mass index (BMI), waist-to-hip ratio (WHR),
      fasting blood glucose (FBG), 2 hour postprandial glucose (2hPG), hemoglobin
      A(1)c(HbA(1)c), total cholesterol(TC), triglycerides (TG), low-density
      lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C) were
      also measured. Of all the patients 89 were divided randomly into group of
      intensive glycemic and lipid control and group of conventional treatment and
      underwent 1 year clinical interview. RESULTS: (1) IMT in patients with T2DM was
      significantly correlated with age(r = 0.515,P = 0.000) , SBP (r = 0.208, P =
      0.025), TC(r = 0.213,P = 0.022), LDL-C(r = 0.253, P = 0.006) and no correlations
      were found between IMT and BMI,WHR,FBG, 2hPG ,HbA(1)c, TG and HDL-C. In
      multivariate regression analysis, age (Beta = 0.527, P = 0.000 )and TC(Beta =
      0.243, P = 0.002) were significant independent determinants for IMT. (3) After 1
      year the change of IMT in the group of intensive glycemic and lipid control was
      significantly different compared with the group of conventional treatment [(
      0.044+/-0.148)mm vs (0.056+/-0.178), P<0.05]. The change of IMT was not
      significantly associated with the use of Metformin, Sulphonylurea and Aspirin,
      but significantly associated with the use of statins. The change of IMT in the
      group using statins was significantly different compared with that in the group
      without using statins[(-0.053+/-0.153)mm vs (0.042+/-0.165)mm, P <0.05].
      CONCLUSION: Carotid IMT appears to be closely related to age and TC in the
      patients with T2DM. long-term intensive glycemic control and lipid control could
      ameliorate the IMT in patients with T2DM. The improvement of IMT may be
      associated with the use of statin drug.

PMID- 18087563
TI  - [Biotransformation of mogroside III by human intestinal bacteria].
AB  - OBJECTIVE: To investigate the biotransformation of mogroside III, one of the main
      chemical constituent in the fruits of Momordica grosvenori Swingle, by the crude
      enzymes of human intestinal bacteria, and determine the structure of
      biotransformation products and provide scientific basis for absorption evaluation
      of primary mogroside III in human intestine. METHODS: The mogroside III was
      incubated with crude enzymes of human intestinal bacteria under the anaerobic
      environment and 37 degrees C condition to transform mogroside III. The
      biotransformation products were isolated and purified by silica gel column
      chromatography, and structurally determined by infra-red (IR) and nuclear
      magnetic resonance (NMR) spectrometry and mass spectroscopy (MS) techniques.
      RESULTS: Mogroside III was converted to mogroside II(A1) and mogrol by successive
      deglycosylation at C-3 of the glucosyl group and C-24 of the gentiobiosyl group.
      CONCLUSION: The human intestinal bacteria showed potent ability to transform
      mogroside III to release secondary glycoside mogroside II(A1) and aglycone
      mogrol.

PMID- 18087564
TI  - [H3N2 subtype of human influenza pneumonia with staphylococcal sepsis and
      staphylococcal pneumonia: report of one case].
AB  - To investigate the clinical characteristics, diagnosis and therapy of influenza
      pneumonia with staphylococcal infection. One patient in our hospital was
      diagnosed and the literatures on the subject were reviewed. The patient presented
      with high fever and dyspnea. Arterial gas analysis indicated type 1 respiratory
      failure. Chest X ray photographs showed bilateral infiltrations and bilateral
      encapsulated pleural effusions. Viral separation and culture of pharyngeal swab
      indicated H(3)N(2) subtype of human influenza virus. Blood, sputum and
      bronchoalveolar lavage fluid (BALF) cultures showed Staphylococcus aureus.
      Pleural effusion was complex parapneumonic pleural effusion. After the
      administration of anti-virus, anti-staphylococcal antibiotics and pleural cavity
      drainage, the patient was cured. The infection of staphylococcus aureus is a
      typical characteristic of influenza pneumonia, and anti-staphylococcal antibiotic
      therapy (with MRSA activity in MRSA endemic regions) should be initiated in
      hospitalized cases of influenza pneumonia. If complex parapneumonic pleural
      effusion or empyema complicated, we should perform pleural cavity drainage in
      time. The oral neuraminidase inhibitor (oseltamivir) could significantly improve
      prognosis.

PMID- 18087565
TI  - [Application of transgenic animal in hypertrophic cardiomyopathy].
AB  - Hypertrophic cardiomyopathy is an autosomal-dominant disease. Disease-causing
      mutations have been found in genes encoding structural components of the thick
      and thin filament systems of cardiac myocyte; it has therefore been named as a
      disease of sarcomere. Many approaches have been used to characterize the
      pathogenesis of the disease. Transgenic animal models have been created to gain
      further insight into the pathogenesis of this disease. Most of these models has
      been made in mice; however, recently a transgenic rabbit model has been created.
      In addition, there are several natural-occurring forms of HCM in animals. The
      discovery of responsible genes and the elucidation of the molecular mechanisms of
      pathogenesis through the use of animal models promise improved and early
      diagnosis and the potential for mechanism-based therapeutics.

PMID- 18087566
TI  - Models of dengue virus infection.
AB  - The need for models of dengue disease has reached a pinnacle as the transmission
      of this mosquito-borne virus has increased dramatically. Little is known about
      the mechanisms that lead to dengue fever and its more severe form, dengue
      hemorrhagic fever; this is owing to the fact that only humans show signs of
      disease. In the past 5 years, research has better identified the initial target
      cells of infection, and this has led to the development of models of infection in
      primary human cell cultures. Mouse-human chimeras, containing these target cells,
      have also led to progress in developing animal models. These advances should soon
      end the stalemate in testing antivirals and vaccine preparations that had
      necessarily been done in incomplete or irrelevant models.

PMID- 18087567
TI  - Arsenic in herbal kelp supplements: concentration, regulations, and labeling.

PMID- 18087568
TI  - Safe use of herbal kelp supplements.

PMID- 18087569
TI  - Organic versus inorganic arsenic in herbal kelp supplements.

PMID- 18087571
TI  - Diet & nutrition: hyperactive ingredients?

PMID- 18087573
TI  - Agriculture: pesticides disrupt nitrogen fixation.

PMID- 18087574
TI  - Particulate matter: the clot thickens: new clues to PM action.

PMID- 18087575
TI  - Chemical exposures: cats as sentinel species.

PMID- 18087577
TI  - Nutrigenomics: the genome--food interface.

PMID- 18087578
TI  - Blue power: turning tides into electricity.

PMID- 18087583
TI  - Electrochemical sensors for the detection of lead and other toxic heavy metals:
      the next generation of personal exposure biomonitors.
AB  - To support the development and implementation of biological monitoring programs,
      we need quantitative technologies for measuring xenobiotic exposure.
      Microanalytical based sensors that work with complex biomatrices such as blood,
      urine, or saliva are being developed and validated and will improve our ability
      to make definitive associations between chemical exposures and disease. Among
      toxic metals, lead continues to be one of the most problematic. Despite
      considerable efforts to identify and eliminate Pb exposure sources, this metal
      remains a significant health concern, particularly for young children. Ongoing
      research focuses on the development of portable metal analyzers that have many
      advantages over current available technologies, thus potentially representing the
      next generation of toxic metal analyzers. In this article, we highlight the
      development and validation of two classes of metal analyzers for the voltammetric
      detection of Pb, including: a) an analyzer based on flow injection analysis and
      anodic stripping voltammetry at a mercury-film electrode, and b) Hg-free metal
      analyzers employing adsorptive stripping voltammetry and novel nanostructure
      materials that include the self-assembled monolayers on mesoporous supports and
      carbon nanotubes. These sensors have been optimized to detect Pb in urine, blood,
      and saliva as accurately as the state-of-the-art inductively coupled plasma-mass
      spectrometry with high reproducibility, and sensitivity allows. These improved
      and portable analytical sensor platforms will facilitate our ability to conduct
      biological monitoring programs to understand the relationship between chemical
      exposure assessment and disease outcomes.

PMID- 18087584
TI  - A systematic review and meta-analysis of interventions used to reduce exposure to
      house dust and their effect on the development and severity of asthma.
AB  - OBJECTIVES: We assessed whether any household dust reduction intervention has the
      effect of increasing or decreasing the development or severity of atopic disease.
      DATA SOURCES: Electronic searches on household intervention and atopic disease
      were conducted in January 2007 in EMBASE, MEDLINE, and the Cochrane Central
      Register of Controlled Trials. No date or language restriction was placed on the
      literature search. DATA EXTRACTION: We included randomized controlled trials
      comparing asthma outcomes in a household intervention group with either placebo
      intervention or no intervention. DATA SYNTHESIS: Fourteen studies met the
      inclusion criteria. Eight recruited antenatally and measured development of
      atopic disease. Six recruited known atopic individuals and measured disease
      status change. Meta-analyses on the prevention studies found that the
      interventions made no difference to the onset of wheeze but made a significant
      reduction in physician-diagnosed asthma. Meta-analysis of lung function outcomes
      indicated no improvement due to the interventions but found a reduction in
      symptom days. Qualitatively, health care was used less in those receiving
      interventions. However, in one study that compared intervention, placebo, and
      control arms, the reduction in heath care use was similar in the placebo and
      intervention arms. CONCLUSIONS: This review suggests that there is not sufficient
      evidence to suggest implementing hygiene measures in an attempt to improve
      outcomes in existing atopic disease, but interventions from birth in those at
      high risk of atopy are useful in preventing diagnosed asthma but not parental
      reported wheeze.

PMID- 18087585
TI  - Cumulative community-level lead exposure and pulse pressure: the normative aging
      study.
AB  - BACKGROUND: Pulse pressure increases with age in industrialized societies as a
      manifestation of arterial stiffening. Lead accumulates in the vasculature and is
      associated with vascular oxidative stress, which can promote functional and
      structural vascular disease. OBJECTIVES: We tested the hypothesis that cumulative
      community-level lead exposure, measured with K-X-ray fluorescence, is associated
      with pulse pressure in a cohort of adult men. METHODS AND RESULTS: In a cross
      sectional analysis of 593 men not treated with antihypertensive medication, tibia
      lead was positively associated with pulse pressure (p < 0.001). Adjusting for
      age, race, diabetes, family history of hypertension, education, waist
      circumference, alcohol intake, smoking history, height, heart rate, fasting
      glucose, and total cholesterol-to-HDL ratio, increasing quintiles of tibia lead
      remained associated with increased pulse pressure (ptrend = 0.02). Men with tibia
      lead above the median (19.0 microg/g) had, on average, a 4.2-mmHg (95% confidence
      interval, 1.9-6.5) higher pulse pressure than men with tibia lead level below the
      median. In contrast, blood lead level was not associated with pulse pressure.
      CONCLUSIONS: These data indicate that lead exposure may contribute to the
      observed increase in pulse pressure that occurs with aging in industrialized
      societies. Lead accumulation may contribute to arterial aging, perhaps providing
      mechanistic insight into the observed association of low-level lead exposure with
      cardiovascular mortality.

PMID- 18087586
TI  - Does the effect of PM10 on mortality depend on PM nickel and vanadium content? A
      reanalysis of the NMMAPS data.
AB  - BACKGROUND: Lack of knowledge regarding particulate matter (PM) characteristics
      associated with toxicity is a crucial research gap. Short-term effects of PM can
      vary by location, possibly reflecting regional differences in mixtures. A report
      by Lippmann et al. [Lippmann et al., Environ Health Perspect 114:1662-1669
      (2006)] analyzed mortality effect estimates from the National Morbidity,
      Mortality, and Air Pollution Study (NMMAPS) for 1987-1994. They found that
      average concentrations of nickel or vanadium in PM2.5 (PM with aerodynamic
      diameter < 2.5 microm) positively modified the lag-1 day association between PM10
      and all-cause mortality. OBJECTIVE: We reestimated the relationship between
      county-specific lag-1 PM10 (PM with aerodynamic diameter < 10 microm) effects on
      mortality and county-specific nickel or vanadium PM2.5 average concentrations
      using 1987-2000 effect estimates. We explored whether such modification is
      sensitive to outliers. METHODS: We estimated long-term average county-level
      nickel and vanadium PM2.5 concentrations for 2000-2005 for 72 U.S. counties
      representing 69 communities. We fitted Bayesian hierarchical regression models to
      investigate whether county-specific short-term effects of PM10 on mortality are
      modified by long-term county-specific nickel or vanadium PM2.5 concentrations. We
      conducted sensitivity analyses by excluding individual communities and
      considering log-transformed data. RESULTS: Our results were consistent with those
      of Lippmann et al. However, we found that when counties included in the NMMAPS
      New York community were excluded from the sensitivity analysis, the evidence of
      effect modification of nickel or vanadium on the short-term effects of PM10
      mortality was much weaker and no longer statistically significant. CONCLUSIONS:
      Our analysis does not contradict the hypothesis that nickel or vanadium may
      increase the risk of PM to human health, but it highlights the sensitivity of
      findings to particularly influential observations.

PMID- 18087587
TI  - Health impacts of estrogens in the environment, considering complex mixture
      effects.
AB  - BACKGROUND: Environmental estrogens in wastewater treatment work (WwTW) effluents
      are well established as the principal cause of reproductive disruption in wild
      fish populations, but their possible role in the wider health effects of
      effluents has not been established. OBJECTIVES: We assessed the contribution of
      estrogens to adverse health effects induced in a model fish species by exposure
      to WwTW effluents and compared effects of an estrogen alone and as part of a
      complex mixture (i.e., spiked into effluent). METHODS: Growth, genotoxic,
      immunotoxic, metabolic, and endocrine (feminized) responses were compared in
      fathead minnows (Pimephales promelas) exposed for 21 days to a potent estrogenic
      effluent, a weakly estrogenic effluent before and after spiking with a steroidal
      estrogen [17 alpha-ethinyl-estradiol (EE2)], and to EE2 alone. RESULTS: In
      addition to endocrine disruption, effluent exposure induced genotoxic damage,
      modulated immune function, and altered metabolism; many of these effects were
      elicited in a sex-specific manner and were proportional to the estrogenic
      potencies of the effluents. A key finding was that some of the responses to EE2
      were modified when it was present in a complex mixture (i.e., spiked into
      effluent), suggesting that mixture effects may not be easily modeled for effluent
      discharges or when the chemicals impact on a diverse array of biological axes.
      CONCLUSION: These data reveal a clear link between estrogens present in effluents
      and diverse, adverse, and sex-related health impacts. Our findings also highlight
      the need for an improved understanding of interactive effects of chemical
      toxicants on biological systems for understanding health effects of environmental
      mixtures.

PMID- 18087588
TI  - Drinking water with uranium below the U.S. EPA water standard causes estrogen
      receptor-dependent responses in female mice.
AB  - BACKGROUND: The deleterious impact of uranium on human health has been linked to
      its radioactive and heavy metal-chemical properties. Decades of research has
      defined the causal relationship between uranium mining/milling and onset of
      kidney and respiratory diseases 25 years later. OBJECTIVE: We investigated the
      hypothesis that uranium, similar to other heavy metals such as cadmium, acts like
      estrogen. METHODS: In several experiments, we exposed intact, ovariectomized, or
      pregnant mice to depleted uranium in drinking water [ranging from 0.5 microg/L
      (0.001 microM) to 28 mg/L (120 microM). RESULTS: Mice that drank uranium
      containing water exhibited estrogenic responses including selective reduction of
      primary follicles, increased uterine weight, greater uterine luminal epithelial
      cell height, accelerated vaginal opening, and persistent presence of cornified
      vaginal cells. Coincident treatment with the antiestrogen ICI 182,780 blocked
      these responses to uranium or the synthetic estrogen diethylstilbestrol. In
      addition, mouse dams that drank uranium-containing water delivered grossly normal
      pups, but they had significantly fewer primordial follicles than pups whose dams
      drank control tap water. CONCLUSIONS: Because of the decades of uranium
      mining/milling in the Colorado plateau in the Four Corners region of the American
      Southwest, the uranium concentration and the route of exposure used in these
      studies are environmentally relevant. Our data support the conclusion that
      uranium is an endocrine-disrupting chemical and populations exposed to
      environmental uranium should be followed for increased risk of fertility problems
      and reproductive cancers.

PMID- 18087589
TI  - Variations in phytoestrogen content between different mill dates of the same diet
      produces significant differences in the time of vaginal opening in CD-1 mice and
      F344 rats but not in CD Sprague-Dawley rats.
AB  - BACKGROUND: The optimum test diet and rodent species/strain for evaluating
      endocrine-disrupting compounds (EDCs) are critical. OBJECTIVES: We conducted
      studies to evaluate rodent species sensitivity and the effects of diets varying
      in phytoestrogen content on the time of vaginal opening (VO) in CD-1 mice,
      Fischer 344 (F344) rats, and CD Sprague-Dawley (S-D) rats. METHODS: Mice were
      weaned on postnatal day (PND) 15 and rats on PND19 and randomly assigned to
      control or test diets. Body weights, food consumption, and time of VO were
      recorded. RESULTS: The time of VO was significantly advanced in F344 rats fed
      diets containing daidzein and genistein, whereas these same diets did not advance
      VO in S-D rats. When animals were fed the AIN-76A diet spiked with genistein,
      time of VO was significantly advanced at all doses in CD-1 mice, at the two
      highest doses in F344 rats, and at the highest dose in S-D rats. The time of VO
      in F344 rats was more highly correlated with the phytoestrogen content than with
      the total metabolizable energy (ME) of 12 diets. CONCLUSIONS: The S-D rat is less
      sensitive to dietary phytoestrogens compared with the F344 rat or the CD-1 mouse,
      suggesting that the S-D rat is not the ideal model for evaluating estrogenic
      activity of EDCs. The profound effects of dietary phytoestrogens on the time of
      VO, an estrogen-sensitive marker, indicate that a standardized open-formula
      phytoestrogen-free diet containing a low ME level should be used to optimize the
      sensitivity of estrogenic bioassays.

PMID- 18087590
TI  - Tetrahydrofurandiol stimulation of phospholipase A2, lipoxygenase, and
      cyclooxygenase gene expression and MCF-7 human breast cancer cell proliferation.
AB  - BACKGROUND: We characterized an endocrine disruptor from ground corncob bedding
      material that interferes with male and female sexual behavior and ovarian
      cyclicity in rats and stimulates estrogen receptor (ER)-positive and ER-negative
      breast cancer cell proliferation. The agents were identified as an isomeric
      mixture of tetrahydrofurandiols (THF-diols; 9,12-oxy-10,13-dihydroxy-octadecanoic
      acid and 10,13-oxy-9,12-dihydroxyoctadecanoic acid). Synthetic THF-diols
      inhibited rat male and female sexual behavior at oral concentrations of 0.5-1
      ppm, and stimulated MCF-7 human breast cancer cell proliferation in vitro.
      OBJECTIVES: Because THF-diols are derived from lipoxygenase and cyclooxygenase
      pathways, we suspected that these compounds may regulate cell proliferation by
      modulating specific enzymatic sites involved in linoleic acid metabolism
      including phospholipase A(2) (PLA2), lipoxygenases (LOX-5 and LOX-12),
      cyclooxygenases (COX-1 and COX-2), and closely coupled enzymes including
      aromatase (AROM). METHODS: MCF-7 human breast cancer cells were treated with
      inhibitors for PLA2 (quinacrine), lipoxygenases (LOX-5 and LOX-12; baicalein, REV
      5091, nordihydroguaiaretic acid), cyclooxygenases (COX-1, COX-2, indomethacin),
      and AROM (formestane). The effects of these enzyme inhibitors on cell
      proliferation in response to THF-diols or estradiol (E(2)) were assessed. THF
      diol modulation of the expression (RNA and protein) of these enzymes was also
      evaluated by quantitative real-time PCR (QPCR) and Western blot analyses.
      RESULTS: The enzyme inhibition and gene expression (RNA and protein) studies
      identified PLA2, LOX-5, LOX-12, COX-2, and perhaps AROM as likely sites of THF
      diol regulation in MCF-7 cells. COX-1 was not affected by THF-diol treatment.
      DISCUSSION: THF-diol stimulation of MCF-7 cell proliferation is mediated through
      effects on the expression of the PLA2, COX-2, LOX-5, and LOX-12 genes and/or
      their respective enzyme activities. The products of these enzymes, including
      prostaglandins, hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecenoic
      acids (HODEs), are well-established mitogens in normal and malignant cells.
      Therefore, it is likely that these compounds are involved in the mechanism of
      action of THF-diols in breast cancer cells. Although the formestane inhibition
      studies suggested that AROM activity might be modulated by THF-diols, this was
      not confirmed by the gene expression studies.

PMID- 18087591
TI  - Effects of chronic and acute ozone exposure on lipid peroxidation and antioxidant
      capacity in healthy young adults.
AB  - BACKGROUND: There is growing evidence for the role of oxidative damage in chronic
      diseases. Although ozone (O3) is an oxidant pollutant to which many people are
      exposed, few studies have examined whether O3 induces oxidative stress in humans.
      OBJECTIVES: This study was designed to assess the effect of short-and long-term
      O(3) exposures on biomarkers of oxidative stress in healthy individuals. METHODS:
      Biomarkers of lipid peroxidation, 8-isoprostane (8-iso-PGF), and antioxidant
      capacity ferric reducing ability of plasma (FRAP) were analyzed in two groups of
      healthy college students with broad ranges of ambient O3 exposure during their
      lifetimes and previous summer recess either in Los Angeles (LA, n = 59) or the
      San Francisco Bay Area (SF, n = 61). RESULTS: Estimated 2-week, 1-month, and
      lifetime O3 exposures were significantly correlated with elevated 8-iso-PGF.
      Elevated summertime exposures resulted in the LA group having higher levels of 8
      iso-PGF than the SF group (p = 0.02). Within each location, males and females had
      similar 8-iso-PGF. No regional difference in FRAP was observed, with
      significantly higher FRAP in males in both groups (SF: p = 0.002; LA: p = 0.004).
      An exposure chamber substudy (n = 15) also showed a significant increase in 8-iso
      PGF as well as an inhibition of FRAP immediately after a 4-hr exposure to 200 ppb
      O3, with near normalization by 18 hr in both biomarkers. CONCLUSIONS: Long-term
      exposure to O3 is associated with elevated 8-iso-PGF, which suggests that 8-iso
      PGF is a good biomarker of oxidative damage related to air pollution.

PMID- 18087592
TI  - Elevated risk of carrying gentamicin-resistant Escherichia coli among U.S.
      poultry workers.
AB  - BACKGROUND: Antimicrobial use in food-animal production is an issue of growing
      concern. The application of antimicrobials for therapy, prophylaxis, and growth
      promotion in broiler chicken production has been associated with the emergence
      and dissemination of antimicrobial-resistant enteric bacteria. Although human
      exposure to antimicrobial-resistant bacteria through food has been examined
      extensively, little attention has been paid to occupational and environmental
      pathways of exposure. OBJECTIVE: Our objective was to measure the relative risk
      for colonization with antimicrobial-resistant Escherichia coli among poultry
      workers compared with community referents. METHODS: We collected stool samples
      and health surveys from 16 poultry workers and 33 community referents in the
      Delmarva region of Maryland and Virginia. E. coli was cultured from stool
      samples, and susceptibility to ampicillin, ciprofloxacin, ceftriaxone,
      gentamicin, nitrofurantoin, and tetracycline was determined for each E. coli
      isolate. We estimated the relative risk for carrying antimicrobial-resistant E.
      coli among poultry workers compared with community referents. RESULTS: Poultry
      workers had 32 times the odds of carrying gentamicin-resistant E. coli compared
      with community referents. The poultry workers were also at significantly
      increased risk of carrying multidrug-resistant E. coli. CONCLUSIONS: Occupational
      exposure to antimicrobial-resistant E. coli from live-animal contact in the
      broiler chicken industry may be an important route of entry for antimicrobial
      resistant E. coli into the community.

PMID- 18087593
TI  - Maternal-fetal transfer of domoic acid in rats at two gestational time points.
AB  - BACKGROUND AND OBJECTIVES: Prenatal exposure to asymptomatic doses of domoic acid
      (DA) causes learning and memory deficits later in life; therefore, we sought to
      measure distribution of DA in maternal plasma and brain, prenatal brain, and
      amniotic fluid 1 hr after exposure, a time frame that normally encompasses acute
      seizure behavior. METHODS: Pregnant rats were given a single intravenous dose of
      DA (0.6 or 1.6 mg/kg body weight) at either gestational day (GD) 13 or GD20,
      which correspond to the beginning of rat embryo neurogenesis and the last day of
      gestation, respectively. Using a direct ELISA, dose-dependent levels of DA were
      detected in each sample matrix tested. RESULTS: An average of 6.6 and 14 ng DA/g
      brain tissue was found in GD13 and GD20 prenatal rats, respectively. Brain
      concentrations of DA in the GD13 prenates were identical to amniotic fluid
      levels, consistent with no restriction for DA to enter the GD13 prenatal brain.
      At GD20 the prenatal brain contained half the concentration of DA in the amniotic
      fluid, and was approximately half that found in the brain of the dams. After 1
      hr, fetal brain and amniotic fluid contained between 1 and 5% of DA found in the
      maternal circulation. The amniotic fluid levels of DA in this study were also
      within the same range measured in stranded California sea lions that showed
      reproductive failure. CONCLUSIONS: DA crosses the placenta, enters brain tissue
      of prenates, and accumulates in the amniotic fluid. Amniotic fluid appears to be
      a useful fluid to monitor DA exposure.

PMID- 18087594
TI  - Prevalence of self-reported diabetes and exposure to organochlorine pesticides
      among Mexican Americans: Hispanic health and nutrition examination survey, 1982
      1984.
AB  - BACKGROUND: The prevalence of diabetes is higher among Mexican Americans than
      among non-Hispanic whites. Higher serum levels of organochlorine pesticides in
      Mexican Americans have been reported. Few studies have explored the association
      between pesticide exposure and diabetes. OBJECTIVES: We set out to examine the
      association between self-reported diabetes and serum concentrations of
      organochlorine pesticides among Mexican Americans residing in the southwestern
      United States from 1982 to 1984. METHODS: This study was conducted among a sample
      of 1,303 Mexican Americans 20-74 years of age from the Hispanic Health and
      Nutrition Examination Survey. Serum concentrations were available for seven
      pesticides or pesticide metabolites at quantifiable levels in at least 1% of the
      study population: p,p'-DDT (dichlorodiphenyltrichloroethane), p,p'-DDE
      (dichlorodiphenyldichloro-ethylene), dieldrin, oxychlordane, beta
      hexachlorocyclohexane, hexachlorobenzene, and trans-nonachlor. We used logistic
      regression to evaluate the association of self-reported diabetes with exposure to
      organochlorine pesticides, with and without adjustment for total serum lipids.
      Nonfasting serum glucose values were compared among exposure groups. RESULTS:
      Self-reported diabetes was significantly associated with serum levels above the
      detectable limit for trans-nonachlor, oxychlordane, and beta
      hexachlorocyclohexane and among those with the highest level of exposure to p,p'
      DDT and p,p'-DDE. On adjustment for total serum lipids, the association with p,p'
      DDT remained significant. Serum glucose levels were elevated among those exposed
      to trans-nonachlor and beta-hexachlorocyclohexane. CONCLUSION: This study
      suggests that higher serum levels of certain organochlorine pesticides may be
      associated with increased prevalence of diabetes. Additional studies with more
      extensive clinical assessment are needed to confirm this association.

PMID- 18087595
TI  - Ambient levels of air pollution induce goblet-cell hyperplasia in human
      conjunctival epithelium.
AB  - BACKGROUND: Ocular mucosa is exposed constantly to the external environment, and
      chronic exposure to air pollution may affect the ocular surface. OBJECTIVE: We
      assessed the effect of air pollution on the ocular surface by combining
      determinations of individual exposure and conjunctival impression cytology.
      METHODS: A panel study was conducted with 29 volunteers recruited in two
      locations with different pollution levels: Sao Paulo (n = 13) and Divinolandia (n
      = 16). We assessed mean individual levels of nitrogen dioxide (NO2) exposure for
      7 days, using a passive sampler. Impression cytology samples were obtained from
      inferior tarsal conjunctiva. Comparisons between the two groups in terms of NO2
      exposure and goblet-cell counts were performed using the Student t-test.
      Correlations between goblet-cells counts and corresponding individual NO2
      exposure levels were determined using Spearman's correlation. RESULTS:
      Individuals living in Sao Paulo received a significantly (p = 0.005) higher dose
      of NO2 (mean 32.47; SD 9.83) than those living in Divinolandia (mean 19.33; SD
      5.24). There was a steady increase in goblet-cell counts, proportional to NO2
      exposure (Spearman's correlation = 0.566, p = 0.001), with a dose-response
      pattern. CONCLUSIONS: A positive and significant association between exposure to
      air pollution and goblet-cell hyperplasia in human conjunctiva was detected. The
      combination of simple measurements of exposure and impression cytology was an
      effective and noninvasive approach for characterizing human response to ambient
      levels of air pollution.

PMID- 18087596
TI  - In utero environmental tobacco smoke exposure alters gene expression in lungs of
      adult BALB/c mice.
AB  - BACKGROUND: In utero environmental tobacco smoke (ETS) exposure exacerbates
      initial lung responses of adult mice to ovalbumin (OVA), a common allergen in
      rodent models of allergic asthma. OBJECTIVE: We tested the hypothesis that in
      utero ETS exposure alters expression of genes (including asthma-related and
      inflammatory genes) in the lungs of adult mice and that this differential
      expression is reflected in differential respiratory and immune responses to
      nontobacco allergens. METHODS: Using Affymetrix Mouse Genome 430 2.0 arrays, we
      examined gene expression changes in lungs of BALB/c mice exposed to ETS in utero,
      OVA, or saline aerosol at weeks 7-8, and OVA sensitization and challenge at weeks
      11-15. Data sets were filtered by transcript p-value (< or = 0.05), false
      discovery rate (< or = 0.05), and fold change (> or = 1.5). Differential
      expression of selected genes was confirmed by polymerase chain reaction (PCR).
      RESULTS: Genes differentially expressed as a result of in utero ETS exposure are
      involved in regulation of biological processes (immune response, cell
      proliferation, apoptosis, cell metabolism) through altered cytoskeleton,
      adhesion, transcription, and enzyme molecules. A number of genes prominent in
      lung inflammation were differentially expressed on PCR but did not pass selection
      criteria for microarray, including arginase (Arg1), chitinases (Chia, Chi3l3,
      Chi3l4), eotaxins (Ccl11, Ccl24), small proline-rich protein 2a (Sprr2a), and
      cytokines (Il4, Il6, Il10, Il13, Tnfa) . CONCLUSION: The differential lung gene
      expression reported here is consistent with previously reported functional
      changes in lungs of mice exposed in utero to ETS and as adults to the nontobacco
      allergen OVA.

PMID- 18087597
TI  - Meeting report: the use of newborn blood spots in environmental research:
      opportunities and challenges.
AB  - INTRODUCTION: Dried blood spots (DBS) are routinely collected from newborns in
      the United States using a heel stick. The DBS are screened for inborn errors of
      metabolism and other disorders. More states are keeping residual spots and making
      them available for research purposes. DNA extraction from the DBS has been widely
      applied; however, the development of methods to measure a range of environmental
      toxicants in DBS has been a more recent goal for laboratory scientists and
      epidemiologists. OBJECTIVES: The purpose of the meeting was to examine the
      utility of DBS to measure environmental exposures. Speakers and discussants were
      invited to present data and discuss approaches to measure a range of analytes
      using DBS. RESULTS: This meeting was held on 20 February 2007 at the University
      of North Carolina at Chapel Hill. The audience consisted of epidemiologists,
      chemists, and staff from state public health programs, the Centers for Disease
      Control and Prevention, and the National Institutes of Health. The meeting
      included presentations on measurement of flame-retarding chemicals and
      pesticides, metals, perchlorate, infectious agents, markers of immune status, and
      protein adducts. Analytical methods included mass spectrometry, atomic
      absorption, molecular methods, and microfluidic techniques. Significant progress
      was reported, but important challenges remain. Concerns including storage
      conditions, sample volume, contamination, and normalization require additional
      systematic evaluation. In addition, DBS storage and access policies require
      coordination. CONCLUSIONS: DBS remain a highly valuable resource for clinical,
      epidemiologic, and toxicologic investigation. The use of DBS to measure
      environmental exposures shows promise but additional work is necessary before
      more widespread use is warranted.

PMID- 18087598
TI  - Meeting report: threats to human health and environmental sustainability in the
      pacific basin.
AB  - The coastal zone of the Pacific Rim is home for about one-third of the world's
      population. Disproportionate growth of Far Eastern economies has produced a
      disproportionate share of related environmental difficulties. As the region
      searches for acceptable compromises between growth and environmental quality, its
      influence on global environmental health is certain to increase. Consequences of
      global environmental change such as habitat alteration, storms, and sea level
      rise will be particularly acute among Pacific Rim nations. Adverse health effects
      from arsenic exposure in Pacific Rim nations have been used to justify drinking
      water standards in the United States and elsewhere. As global manufacturing in
      the Pacific Rim increases, the centroid of global air quality and waste
      management issues will shift further toward Far Eastern nations. The Eleventh
      International Conference of the Pacific Basin Consortium (PBC) was held in
      September 2005 in Honolulu, Hawaii. The purpose of the conference was to bring
      together individuals to discuss regional challenges to sustainable growth. The
      historic emphasis of the conference on hazardous wastes in relation to human
      health makes the PBC an ideal forum for discussing technical aspects of
      sustainable economic growth in the Pacific region. That role is reflected in the
      2005 PBC conference themes, which included management of arsenic in potable
      waters, air quality, climate change, pesticides, mercury, and electronics
      industry waste-each with emphasis on relationships to human health. Arsenic
      management exemplifies the manner in which the PBC can focus interdisciplinary
      discussion in a single technical area. The conference program provided talks on
      arsenic toxicology, treatment technologies, management of arsenic-bearing
      residuals from water treatment, and the probable societal costs and benefits of
      arsenic management.

PMID- 18087599
TI  - Case report: a metabolic disorder presenting as pediatric manganism.
AB  - CONTEXT: Manganese is a trace element, essential for physiologic functioning but
      neurotoxic at high doses. Common exposure sources include dietary intake as well
      as drinking water in some regions; toxicity is most often associated with
      inhalation exposures in occupational settings. In this article we describe the
      investigation of a pediatric case of manganism using both clinical and
      environmental assessment methods. CASE PRESENTATION: A previously healthy 6-year
      old child presented with severe Mn neurotoxicity, iron deficiency, and elevated
      cobalt levels. Immediate and selected extended family members had elevated plasma
      Mn but remained asymptomatic. An exposure assessment identified seasonal
      ingestion exposures to Mn at the family's summer cottage; these were common to
      the four immediate family members. Well water used for drinking and cooking
      exceeded recommended guidelines, and foods high in Mn predominated in their diet.
      No inhalation exposures were identified. Only pica was unique to the patient.
      DISCUSSION: The combined evidence of the environmental assessment and
      biomonitoring of blood Mn levels supported a seasonal ingestion exposure source;
      this alone was insufficient to explain the toxicity because the patient's 7-year
      old sibling was asymptomatic with almost identical exposures (except pica). A
      metabolic disorder involving divalent metals (Mn, Fe, and Co) interacting with
      environmental exposures is the most likely explanation. RELEVANCE TO CLINICAL OR
      PROFESSIONAL PRACTICE: This case report adds to the emerging body of evidence
      linking neurologic effects to ingestion Mn exposure.

PMID- 18087600
TI  - Association of thyroid hormone concentrations with levels of organochlorine
      compounds in cord blood of neonates.
AB  - BACKGROUND: Thyroid hormones are important regulators of brain development.
      During critical periods of development, even transient disorders in thyroid
      hormone availability may lead to profound neurologic impairment. Animal
      experiments have shown that certain environmental pollutants, including heavy
      metals and organochlorine compounds such as polychlorinated biphenyls (PCBs) and
      dioxins, can interfere with thyroid hormone homeostasis. Whether these
      contaminants can affect circulating levels of thyroid hormones in humans is
      unclear, however, because the results of available studies are inconsistent.
      OBJECTIVES: The aim of the present study is to examine the possible relationships
      between concentrations of environmental pollutants and thyroid hormone levels in
      human umbilical cord blood. METHODS: We measured concentrations of environmental
      pollutants [including selected PCBs, dioxin-like compounds, hexachlorobenzene,
      p,p'-DDE (dichlorodiphenyldichloroethylene), cadmium, lead] and thyroid hormones
      in the cord blood of 198 neonates. RESULTS: A statistically significant inverse
      relationship between concentrations of organochlorine compounds and levels of
      both free triiodothyronine (fT3) and free thyroxine (fT4), but not thyroid
      stimulating hormone, was observed. We found no association between concentrations
      of heavy metals and thyroid hormone levels. CONCLUSIONS: Our results suggest that
      environmental chemicals may affect the thyroid system of human neonates. Although
      the differences in fT3 and fT4 levels associated with the organochlorine
      compounds were within the normal range, the observed interferences may still have
      detrimental effects on the neurologic development of the individual children,
      given the importance of thyroid hormones in brain development.

PMID- 18087601
TI  - Household exposure to pesticides and risk of childhood hematopoietic
      malignancies: The ESCALE study (SFCE).
AB  - OBJECTIVES: We investigated the role of household exposure to pesticides in the
      etiology of childhood hematopoietic malignancies. METHODS: The national registry
      based case-control study ESCALE (Etude sur les cancers de l'enfant) was carried
      out in France over the period 2003-2004. Population controls were frequency
      matched with the cases on age and sex. Maternal household use of pesticides
      during pregnancy and paternal use during pregnancy or childhood were reported by
      the mothers in a structured telephone questionnaire. Insecticides (used at home,
      on pets, or for garden crops), herbicides, and fungicides were distinguished. We
      estimated odds ratios (ORs) using unconditional regression models closely
      adjusting for age, sex, degree of urbanization, and type of housing (flat or
      house). RESULTS: We included a total of 764 cases of acute leukemia (AL), 130 of
      Hodgkin lymphoma (HL), 166 of non-Hodgkin lymphoma (NHL), and 1,681 controls.
      Insecticide use during pregnancy was significantly associated with childhood AL
      [OR = 2.1; 95% confidence interval (CI), 1.7-2.5], both lymphoblastic and
      myeloblastic, NHL (OR = 1.8; 95% CI, 1.3-2.6), mainly for Burkitt lymphoma (OR =
      2.7; 95% CI, 1.6-4.5), and mixed-cell HL (OR = 4.1; 95% CI, 1.4-11.8), but not
      nodular sclerosis HL (OR = 1.1; 95% CI, 0.6-1.9). Paternal household use of
      pesticides was also related to AL (OR = 1.5; 95% CI, 1.2-1.8) and NHL (OR = 1.7;
      95% CI, 1.2-2.6); but for AL the relationships did not remain after adjustment
      for maternal pesticide use during pregnancy. CONCLUSION: The study findings
      strengthen the hypothesis that domestic use of pesticides may play a role in the
      etiology of childhood hematopoietic malignancies. The consistency of the findings
      with those of previous studies on AL raises the question of the advisability of
      preventing pesticide use by pregnant women.

PMID- 18087602
TI  - Determinants of prenatal exposure to polychlorinated biphenyls (PCBs) and
      polybrominated diphenyl ethers (PBDEs) in an urban population.
AB  - BACKGROUND: Recent studies have reported blood levels of polybrominated diphenyl
      ethers (PBDEs) in the U.S. population. Information about neonatal levels and
      about the relationship to polychlorinated biphenyls (PCBs) exposures is limited.
      OBJECTIVES: The objective was to characterize levels and determinants of fetal
      exposure to PBDEs and PCBs among newborns from Baltimore, Maryland. METHODS: We
      analyzed umbilical cord blood for eight PBDEs and 35 PCBs from infants delivered
      at the Johns Hopkins Hospital. Maternal and infant characteristics were
      abstracted from medical records. RESULTS: Ninety-four percent of cord serum
      samples had quantifiable levels of at least one PBDE congener, and > 99% had at
      least one detectable PCB congener. PBDE concentrations in cord blood were similar
      to those reported in other studies from North America. Strong correlations were
      observed within but not across PCB and PBDE classes. Multivariate models showed
      that many factors independently predicted exposure to BDE-47, BDE-100, and BDE
      153 and CB-118, CB-138/158, CB-153, and CB-180. Generally, infants of Asian
      mothers had lower PBDE and PCB levels, and infants of smokers had higher levels.
      Increased maternal body mass index was associated with lower levels of PCBs but
      not PBDEs. Levels of PCBs but not PBDEs were lower in births from married and
      multiparous mothers. Increased maternal age was associated with higher PCB levels
      but lower PBDE levels. CONCLUSIONS: Although many of the factors we investigated
      were independent predictors of both PBDE and PCB levels, in some cases the
      direction of associations was different. More research is needed to better
      understand the sources and pathways of PBDE exposure.

PMID- 18087603
TI  - Chernobyl: relationship between the number of missing newborn boys and the level
      of radiation in the Czech regions.
AB  - BACKGROUND: The number of newborn boys was higher than that of girls in the Czech
      Republic each month from 1950 to 2005. The only exception was November 1986, when
      the number of newborn boys was significantly reduced. This has been explained by
      a selective negative impact of the Chernobyl accident in April 1986 on male
      fetuses during the third month of their prenatal development. OBJECTIVES: The
      first and most radioactive cloud passed over the Czech Republic during 30 April-1
      May 1986. Concurrent rainfall multiplied the radioactivity by up to > 10,000-fold
      in specific regions. We verified a hypothesis that the decrease in the male birth
      fraction in November 1986 correlated with the level of radiation in eight Czech
      regions after the Chernobyl disaster. RESULTS: We found a relationship between
      the level of radiation and the decrease in the number of newborn boys. The number
      of newborn boys was decreased in the six eastern regions where the radiation was
      strongly increased due to rain that accompanied the radioactive cloud. In
      contrast, the number of newborn boys was not reduced in the two western regions
      where the radioactivity was markedly lower. CONCLUSIONS: A negative impact of
      radiation on the prenatal population was manifested as a selective loss of
      newborn boys in November 1986. This loss correlated with level of radioactivity.
      The 131I probably played the most important role because of its up-take during
      primary saturation of fetal thyroid by iodine, which accompanies the onset of the
      gland function in 3-month-old fetuses.

PMID- 18087604
TI  - Management of arthralgias associated with aromatase inhibitor therapy.
AB  - For the upfront adjuvant therapy of postmenopausal estrogen receptor-positive
      breast cancer, the third-generation aromatase inhibitors (AIS) have shown a more
      favourable overall risk-benefit profile than has tamoxifen. Benefits of the ais
      include less frequent gynecologic, cerebrovascular, and thromboembolic adverse
      events; greater disease-free survival; and lower tumour recurrence. Although
      approximately 25% of postmenopausal women with early breast cancer report
      experiencing symptoms of arthralgia with ai therapy, 68-month data from the
      Arimidex, Tamoxifen, Alone or in Combination trial showed that, compared with
      tamoxifen, anastrozole treatment was associated with only a modest increase in
      the incidence of joint symptoms. The events, which were mostly mild-to-moderate
      in intensity, led to treatment withdrawal in 2% of patients on anastrozole as
      compared with 1% in the tamoxifen arm. The symptoms and changes correlate with
      clinical, biochemical, and radiologic findings in symptomatic women. To determine
      appropriate intervention, it is therefore essential to perform a comprehensive
      evaluation of musculoskeletal complaints to distinguish natural menopause-related
      degenerative disease from AI-related effects. The present review explores the
      advantages of differential diagnosis with an emphasis on history and physical and
      musculoskeletal examination; laboratory investigations are used to corroborate or
      rule out clinical impressions. The transient symptoms associated with the ais are
      manageable with an appropriate combination of lifestyle changes, including
      exercise and joint protection in conjunction with pharmacologic approaches.

PMID- 18087606
TI  - Cancer therapy disparity: unequal access to breast cancer therapeutics and drug
      funding in Canada.
AB  - Adjuvant therapy has made a significant contribution in reducing breast cancer
      specific mortality. Standard chemotherapeutics and tamoxifen have been the
      mainstay treatment for years, but recent clinical evidence supports the use of
      novel small-molecule therapy and aromatase inhibitor therapy in selected
      settings, challenging not only the traditional paradigm of breast cancer
      treatment, but also provincial funding of oncologic care across Canada. The
      disparity in access to aromatase inhibitor therapy for postmenopausal women with
      early-stage hormone-sensitive breast cancer across Canada is highlighted as an
      example.

PMID- 18087605
TI  - Management of sexual dysfunction in postmenopausal breast cancer patients taking
      adjuvant aromatase inhibitor therapy.
AB  - Treatment with aromatase inhibitors for postmenopausal women with breast cancer
      has been shown to reduce or obviate invasive procedures such as hysteroscopy or
      curettage associated with tamoxifen-induced endometrial abnormalities. The side
      effect of upfront aromatase inhibitors, diminished estrogen synthesis, is similar
      to that seen with the natural events of aging. The consequences often include
      vasomotor symptoms (hot flushes) and vaginal dryness and atrophy, which in turn
      may result in cystitis and vaginitis. Not surprisingly, painful intercourse
      (dyspareunia) and loss of sexual interest (decreased libido) frequently occur as
      well. Various interventions, both non-hormonal and hormonal, are currently
      available to manage these problems. The purpose of the present review is to
      provide the practitioner with a wide array of management options to assist in
      treating the sexual consequences of aromatase inhibitors. The suggestions in this
      review are based on recent literature and on the recommendations set forth both
      by the North American Menopause Association and in the clinical practice
      guidelines of the Society of Gynaecologists and Obstetricians of Canada. The
      complexity of female sexual dysfunction necessitates a biopsychosocial approach
      to assessment and management alike, with interventions ranging from education and
      lifestyle changes to sexual counselling, pelvic floor therapies, sexual aids,
      medications, and dietary supplements-all of which have been reported to have a
      variable, but often successful, effect on symptom amelioration. Although the use
      of specific hormone replacement-most commonly local estrogen, and less commonly,
      systemic estrogen with or without an androgen, progesterone, or the additional of
      an androgen in an estrogenized woman (or a combination)-may be highly effective,
      the concern remains that in patients with estrogen-dependent breast cancer,
      including those receiving anti-estrogenic adjuvant therapies, the use of these
      hormones may be attended with potential risk. Therefore, non-hormonal
      alternatives should in all cases be initially tried with the expectation that
      symptomatic relief can often be achieved.First-line therapy for urogenital
      symptoms, notably vaginal dryness and dyspareunia, should be the non-hormonal
      group of preparations such as moisturizers and precoital vaginal lubricants. In
      patients with estrogen-dependent breast cancer (notably those receiving anti
      estrogenic adjuvant therapies) and severely symptomatic vaginal atrophy that
      fails to respond to non-hormonal options, menopausal hormone replacement or
      prescription vaginal estrogen therapy may considered. Systemic estrogen may be
      associated with risk and thus is best avoided. Judicious use of hormones may be
      appropriate in the well-informed patient who gives informed consent, but given
      the potential risk, these agents should be prescribed only after mutual agreement
      of the patient and her oncologist.

PMID- 18087609
TI  - Diamond microelectrodes for in vitro electroanalytical measurements: current
      status and remaining challenges.
AB  - An emerging research field in electrochemistry today is the preparation,
      characterization and application of diamond microelectrodes for electroanalytical
      measurements in biological media. Interest in this new electrode material stems
      from its outstanding properties: (i) hardness, (ii) low, stable and pH
      independent background current, (iii) morphological and microstructural stability
      over a wide range of potentials, (iv) good electrochemical responsiveness for
      multiple redox analytes without any conventional pre-treatment and (v) weak
      molecular adsorption of polar molecules that leads to a high level of resistance
      to response deactivation and electrode fouling. Diamond electrodes have advanced
      in recent years from being simply a scientific curiosity into a viable material
      for electroanalysis. In this article, we highlight the current state of progress
      by our laboratory and others on the preparation, study of the basic
      electrochemical properties, and application of this new type of microelectrode
      for in vitro electroanalytical measurements, and discuss some of the remaining
      challenges.

PMID- 18087610
TI  - Is there a future for sequential chemical extraction?
AB  - Since their introduction in the late 1970s, sequential extraction procedures have
      experienced a rapid increase in use. They are now applied for a large number of
      potentially toxic elements in a wide range of sample types. This review uses
      evidence from the literature to consider the usefulness and limitations of
      sequential extraction and thereby to assess its future role in environmental
      chemical analysis. It is not the intention to provide a comprehensive survey of
      all applications of sequential extractions or to consider the merits and
      disadvantages of individual schemes. These aspects have been covered adequately
      in other, recent reviews. This review focuses in particular on various key issues
      surrounding sequential extractions such as nomenclature, methodologies,
      presentation of data and interpretation of data, and discusses typical
      applications from the recent literature for which sequential extraction can
      provide useful and meaningful information. Also covered are emerging developments
      such as accelerated procedures using ultrasound- or microwave energy-assisted
      extractions, dynamic extractions, the use of chemometrics, the combination of
      sequential extraction with isotope analysis, and the extension of the approach to
      non-traditional analytes such as arsenic, mercury, selenium and radionuclides.

PMID- 18087611
TI  - Characterisation of organometallic and coordination compounds by solvent-free
      matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry.
AB  - Insoluble or low solubility organometallic and coordination compounds have been
      characterised by matrix-assisted laser desorption/ionisation time-of-flight mass
      spectrometry, with solvent-free sample preparation being the key step toward
      successful analysis.

PMID- 18087612
TI  - The characteristic red chemiluminescence from reactions with acidic potassium
      permanganate: further spectroscopic evidence for a manganese(II) emitter.
AB  - A direct comparison of the laser-induced photoluminescence of manganese(ii) with
      the chemiluminescence from the reaction between acidic potassium permanganate and
      sodium borohydride was used to confirm that the characteristic red emission from
      this widely used chemiluminescence reagent emanates from an electronically
      excited manganese(ii) species.

PMID- 18087613
TI  - Direct acoustic profiling of DNA hybridisation using HSV type 1 viral sequences.
AB  - We describe the detection of specific, conserved DNA sequences of herpes simplex
      virus (HSV) type 1 by means of a novel, high sensitivity acoustic biosensor.
      Repeated assays on planar and polymeric carboxylic acid- and biotin-presenting
      surface chemistries enabled statistical comparison of assay specificity and
      sensitivity and evaluation of assay Z-factor scores. Using a three minute
      hybridisation with NeutrAvidin capture for signal enhancement, it was possible to
      detect HSV viral nucleic acids at 5.2 x 10(-11) M concentration.

PMID- 18087614
TI  - Real-time monitoring of powder mixing in a convective blender using non-invasive
      reflectance NIR spectrometry.
AB  - A convective blender based on a scaled down version of a high shear mixer
      granulator was used to produce binary mixtures of microcrystalline cellulose
      (Avicel) and aspirin, citric acid, aspartame or povidone. Spectra of stationary
      Avicel or aspirin powder provided an indication of the information depth achieved
      with the NIR spectrometer used in the study, and confirmed previously reported
      effects of particle size and wavenumber. However, it was demonstrated that for
      10% w/w aspirin in Avicel, the information depth at the C-H second overtone of
      aspirin (about 2.4 mm) was unaffected by changes in the particle size of aspirin
      and was determined by the major component. By making non-invasive NIR
      measurements as powders were mixed, it was possible to illustrate differences in
      the mixing characteristics of aspirin, citric acid, aspartame or povidone with
      Avicel, which were related to differences in the cohesive properties of the
      particles. Mixing profiles based on second overtone signals were better for
      quantitative analysis than those derived from first overtone measurements. It was
      also demonstrated that the peak-to-peak noise of the mixing profile obtained from
      the second overtone of aspirin changed linearly with the particle size of aspirin
      added to Avicel. Hence, measurement of the mixing profile in real time with NIR
      spectrometry provided simultaneously the opportunity to study the dynamics of
      powder mixing, make quantitative measurements and monitor possible changes in
      particle size during blending.

PMID- 18087615
TI  - A 'turn-on' FRET peptide sensor based on the mercury binding protein MerP.
AB  - A new fluorescent peptidyl chemosensor based on the mercury binding MerP protein
      with fluorescence resonance energy transfer (FRET) capabilities has been
      synthesized via Fmoc solid-phase peptide synthesis. The metal chelating unit,
      which is flanked by the fluorophores tryptophan (donor) and dansyl (acceptor),
      contains amino acids from MerP's metal binding loop (sequence: dansyl-Gly-Gly-Thr
      Leu-Ala-Val-Pro-Gly-Met-Thr-Cys-Ala-Ala-Cys-Pro-Ile-Thr-Val-Lys-Lys-Gly-Gly-Trp
      CONH(2)). A FRET enhancement or 'turn-on' response was observed for Hg(2+) as
      well as for Zn(2+), Cd(2+) and Ag(+) in a pure aqueous solution at pH 7.0. The
      emission intensity of the acceptor was used to monitor the concentration of these
      metals ions with detection limits of 280, 6, 103 and 496 microg L(-1),
      respectively. No response was observed for the other transition, alkali and
      alkaline earth metals tested. The fluorescent enhancement observed is unique for
      Hg(2+) since this metal generally quenches fluorescence. The acceptor
      fluorescence increase resulting from metal binding-induced FRET suggests a sensor
      that is inherently more sensitive than one based on quenching by the binding
      event.

PMID- 18087616
TI  - An optical sensor for reactive oxygen species: encapsulation of functionalised
      silica nanoparticles into silicate nanoprobes to reduce fluorophore leaching.
AB  - Sol-gel nanoprobes, also known as Photonic Explorer for Bioanalysis with
      Biologically Localised Embedding (PEBBLE), capable of performing in-vitro
      intracellular monitoring of reactive oxygen species have been developed using a
      modified form of 5(6)-carboxyfluorescein diacetate. A sol-gel matrix was selected
      for the design of the probes as it is photostable, optically transparent and
      chemically inert, and to minimise leaching of the dye from the porous matrix it
      was covalently immobilised to silica nanoparticles (15 nm). Using this approach,
      0.1% of the dye was found to leach over a typical analysis time of 5 h and
      minimal photobleaching was observed. In addition, the nanoprobes were shown to
      respond to hydrogen peroxide, hydroxyl anions, nitric oxide, peroxynitrile and
      superoxide anions, obtaining limits of detection of 2.2, 1.1, 3.2, 1.1 and 1.1 nM
      respectively. The nanoprobes were subsequently introduced into bovine oviducts
      using a lipid transfection reagent (Escort IV) and fluorescence was observed.

PMID- 18087617
TI  - Changes in interfacial properties of alpha-synuclein preceding its aggregation.
AB  - Parkinson's disease (PD) is associated with the formation and deposition of
      amyloid fibrils of the protein alpha-synuclein (AS). It has been proposed that
      oligomeric intermediates on the pathway to fibrilization rather than the fibrils
      themselves are the pathogenic agents of PD, but efficient methods for their
      detection are lacking. We have studied the interfacial properties of wild-type AS
      and the course of its aggregation in vitro using electrochemical analysis and
      dynamic light scattering. The oxidation signals of tyrosine residues of AS at
      carbon electrodes and the ability of fibrils to adsorb and catalyze hydrogen
      evolution at hanging mercury drop electrodes (HMDEs) decreased during incubation.
      HMDEs were particularly sensitive to pre-aggregation changes in AS. Already after
      1 h of a standard aggregation assay in vitro (stirring at 37 degrees C), the
      electrocatalytic peak H increased greatly and shifted to less negative
      potentials. Between 3 and 9 h of incubation, an interval during which dynamic
      light scattering indicated AS oligomerization, peak H diminished and shifted to
      more negative potentials, and AS adsorbability decreased. We tentatively
      attribute the very early changes in the interfacial behavior of the protein after
      the first few hours of incubation to protein destabilization with disruption of
      long-range interactions. The subsequent changes can be related to the onset of
      oligomerization. Our results demonstrate the utility of electrochemical methods
      as new and simple tools for the investigation of amyloid formation.

PMID- 18087618
TI  - Surface immobilisation and properties of smooth muscle cells monitored by on-line
      acoustic wave detector.
AB  - The attachment of rat aortic smooth muscle cells to various surfaces has been
      monitored by a thickness shear mode acoustic wave device incorporated into an on
      line configuration. Using the total injection analysis method, laminin and
      fibronectin were adsorbed to the device surface, to be followed by introduction
      of cells into the system. The results of these experiments in terms of frequency
      and motional resistance measurements were also compared with those for cell
      attachment to the bare gold electrode of the sensor. The responses of the surface
      bound cells to the introduction of various ions, depolarisation events and damage
      subsequent to exposure to hydrogen peroxide were also observed. Morphological
      changes in the cells, as confirmed by scanning electron microscopy, are
      correlated with results of the acoustic wave measurements.

PMID- 18087619
TI  - The development of an immobilized enzyme reactor containing glyceraldehyde-3
      phosphate dehydrogenase from Trypanosoma cruzi: the effect of species' specific
      differences on the immobilization.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in the
      life cycle of the Trypanosoma cruzi, and an immobilized enzyme reactor (IMER) has
      been developed for use in the on-line screening for GAPDH inhibitors. An IMER
      containing human GAPDH has been previously reported; however, these conditions
      produced a T. cruzi GAPDH-IMER with poor activity and stability. The factors
      affecting the stability of the human and T. cruzi GAPDHs in the immobilization
      process and the influence of pH and buffer type on the stability and activity of
      the IMERs have been investigated. The resulting T. cruzi GAPDH-IMER was coupled
      to an analytical octyl column, which was used to achieve chromatographic
      separation of NAD(+) from NADH. The production of NADH stimulated by d
      glyceraldehyde-3-phosphate was used to investigate the activity and kinetic
      parameters of the immobilized T. cruzi GAPDH. The Michaelis-Menten constant
      (K(m)) values determined for d-glyceraldehyde-3-phosphate and NAD(+) were K(m) =
      0.5 +/- 0.05 mM and 0.648 +/- 0.08 mM, respectively, which were consistent with
      the values obtained using the non-immobilized enzyme.

PMID- 18087620
TI  - Enzyme-catalyzed signal amplification for electrochemical DNA detection with a
      PNA-modified electrode.
AB  - The signal amplification technique of peptide nucleic acid (PNA)-based
      electrochemical DNA sensor was developed in a label-free and one-step method
      utilizing enzymatic catalysis. Electrochemical detection of DNA hybridization on
      a PNA-modified electrode is based on the change of surface charge caused by the
      hybridization of negatively charged DNA molecules. The negatively charged
      mediator, ferrocenedicarboxylic acid, cannot diffuse to the DNA hybridized
      electrode surface due to the charge repulsion with the hybridized DNA molecule
      while it can easily approach the neutral PNA-modified electrode surface without
      the hybridization. By employing glucose oxidase catalysis on this PNA-based
      electrochemical system, the oxidized mediator could be immediately reduced
      leading to greatly increased electrochemical signals. Using the enzymatic
      strategy, we successfully demonstrated its clinical utility by detecting one of
      the mutation sequences of the breast cancer susceptibility gene BRCA1 at a sample
      concentration lower than 10(-9) M. Furthermore, a single base-mismatched sample
      could be also discriminated from a perfectly matched sample.

PMID- 18087621
TI  - Qualitative evaluation of chromatographic data from quality control schemes using
      a support vector machine.
AB  - The qualitative evaluation of chromatographic data in the framework of external
      quality assurance schemes is considered in this paper. The homogeneity in the
      evaluation of chromatographic data among human experts in samples with analytes
      close to the limit of detection of analytical methods was examined and also a
      Support Vector Machine (SVM) was developed as an alternative to experts for a
      more homogeneous and automatic evaluation. A set of 105 ion chromatograms
      obtained by anti-doping control laboratories was used in this study. The quality
      of the ion chromatograms was evaluated qualitatively by nine independent experts
      (associating a score from 0 to 4) and also more objectively taking into account
      chromatographic parameters (peak width, asymmetry, resolution and S/N ratio).
      Results obtained showed a high degree of variability among experts when judging
      ion chromatograms. Experts applying extremely outlying evaluation criteria were
      identified and excluded from the data used to develop the SVM. This machine was
      built providing the system with qualitative information (scores assigned by
      experts) and with objective data (parameters) of the ion chromatograms. A seven
      fold cross-validation approach was used to train and to evaluate the predictive
      ability of the machine. According to the results obtained, the SVM developed was
      found to be close to the reasoning process followed by the homogeneous human
      expert group. This machine also could provide a scoring system to sort
      laboratories according to the quality of their results. The qualitative
      evaluation of analytical records using a scoring system allowed the
      identification of the main factors affecting the quality of chromatographic
      analytical data, such as the specific analytical technique applied and the
      adherence to guidelines for reporting positive results.

PMID- 18087622
TI  - Potential shift correction in multivariate curve resolution of voltammetric data.
      General formulation and application to some experimental systems.
AB  - A new mathematical algorithm is proposed to correct the progressive potential
      shift of some voltammetric signals that decrease the linearity of the data. The
      corrected data matrix can be further analysed by Multivariate Curve Resolution by
      Alternating Least Squares (MCR-ALS) and the vector including the potential shift
      corrections can be fitted to specific equations such as that by DeFord-Hume. A
      detailed discussion is given on the different cases of potential shift
      correction, and, in some of them, mathematical simulation is made or experimental
      systems [Cd(ii)-glutathione and Zn(ii)-glycine] are analysed.

PMID- 18087623
TI  - An improved sensitivity non-enzymatic glucose sensor based on a CuO nanowire
      modified Cu electrode.
AB  - CuO nanowires have been prepared and applied for the fabrication of glucose
      sensors with highly enhanced sensitivity. Cu(OH)(2) nanowires were initially
      synthesised by a simple and fast procedure, CuO nanowires were then formed simply
      by removing the water through heat treatment. The structures and morphologies of
      Cu(OH)(2) and CuO nanowires were characterised by X-ray diffraction, X-ray
      photoelectron spectroscopy, scanning electron microscopy, and transmission
      electron microscopy. The direct electrocatalytic oxidation of glucose in alkaline
      medium at CuO nanowire modified electrodes has been investigated in detail.
      Compared to a bare Cu electrode, a substantial decrease in the overvoltage of the
      glucose oxidation was observed at the CuO nanowire electrodes with oxidation
      starting at ca. 0.10 V vs. Ag/AgCl (saturated KCl). At an applied potential of
      0.33 V, CuO nanowire electrodes produce high and reproducible sensitivity to
      glucose with 0.49 microA/micromol dm(-3). Linear responses were obtained over a
      concentration range from 0.40 micromol dm(-3) to 2.0 mmol dm(-3) with a detection
      limit of 49 nmol dm(-3) (S/N = 3). The CuO nanowire modified electrode allows
      highly sensitive, low working potential, stable, and fast amperometric sensing of
      glucose, thus is promising for the future development of non-enzymatic glucose
      sensors.

PMID- 18087624
TI  - Enhanced stability and sensitivity of ionic liquid-carbon paste electrodes at
      elevated temperatures.
AB  - We describe the operation of ionic liquid-carbon paste electrodes at elevated
      temperatures and the effect of heating on the electrode performance and response.
      Using cyclic and square wave voltammetry and amperometry, it is shown that
      signals can be enhanced and stabilized by increasing the temperature of the
      operating solution. At low temperature, the electrode was susceptible to
      electrode fouling and showed poor stability, sensitivity, and linearity. An order
      of magnitude improvement of response for ascorbic acid was possible by operating
      the electrode at 60 degrees C compared to 0 degrees C. This study represents the
      first report showing that the analytical response of ionic liquid-carbon paste
      electrodes can be improved by operating them at elevated temperatures for a
      number of applications.

PMID- 18087625
TI  - Application of thermotolerant microorganisms for biofertilizer preparation.
AB  - BACKGROUND AND PURPOSE: Intensive agriculture is practised in Taiwan, and compost
      application is very popular as a means of improving the soil physical properties
      and supplying plant nutrition. We tested the potential of inoculation with
      thermotolerant microorganisms to shorten the maturity and improve the quality of
      biofertilizer prepared by composting. METHODS: Thermotolerant microorganisms were
      isolated from compost and reinoculated for the preparation of biofertilizer. The
      physical, chemical and biological properties of the biofertilizer were determined
      during composting. The effects of biofertilizer application on the growth and
      yield of rape were also studied. RESULTS: Among 3823 colonies of thermotolerant
      microorganisms, Streptomyces thermonitrificans NTU-88, Streptococcus sp. NTU-130
      and Aspergillus fumigatus NTU-132 exhibited high growth rates and cellulolytic
      and proteolytic activities. When a mixture of rice straw and swine manure were
      inoculated with these isolates and composted for 61 days, substrate temperature
      increased initially and then decreased gradually during composting. Substrate pH
      increased from 7.3 to 8.5. Microbial inoculation enhanced the rate of maturity,
      and increased the content of ash and total and immobilized nitrogen, improved the
      germination rate of alfalfa seed, and decreased the content of total organic
      carbon and the carbon/nitrogen ratio. Biofertilizer application increased the
      growth and yield of rape. CONCLUSIONS: Inoculation of thermotolerant and
      thermophilic microorganisms to agricultural waste for biofertilizer preparation
      enhances the rate of maturity and improves the quality of the resulting
      biofertilizer. Inoculation of appropriate microorganisms in biofertilizer
      preparation might be usefully applied to agricultural situations.

PMID- 18087626
TI  - Clinical characteristics of non-O1/non-O139 Vibrio cholerae isolates and
      polymerase chain reaction analysis of their virulence factors.
AB  - BACKGROUND AND PURPOSE: Non-O1/non-O139 Vibrio cholerae can cause invasive
      extraintestinal disease as well as enteritis. The pathogenesis of invasive non
      O1/non-O139 V. cholerae infections remains to be determined. This study compared
      the clinical manifestations and predisposing factors between bacteremic and non
      bacteremic non-O1/non-O139 V. cholerae infections and examined virulence
      associated genes in the pathogenic strains causing invasive disease. METHODS: We
      retrospectively investigated clinical characteristics of 18 bacteremic patients
      and 18 non-bacteremic patients, including demographic, laboratory and clinical
      data. Fourteen clinical isolates (ten isolated from blood and four from stool
      specimens) were obtained for polymerase chain reaction tests of the presence of
      virulence-associated genes ctxA, ctxB and tcpA. RESULTS: There was no difference
      in age, gender and gastrointestinal symptoms including abdominal pain and
      diarrhea, laboratory findings including leukocytosis and anemia, or underlying
      immunocompromised condition, except cirrhosis, between the bacteremic and non
      bacteremic groups. Compared to patients with non-bacteremic infections, patients
      with non-O1/non-O139 V. cholerae bacteremia were significantly more likely to
      have cirrhosis and thrombocytopenia (0.0% vs 77.8% and 5.9% vs 72.2%,
      respectively; p<0.001). The cholera toxin genes (ctxA and ctxB) were found in
      only one strain (isolated from the stool specimen of a patient with enteritis)
      among fourteen clinical strains (7%). The tcpA gene, encoding the toxin
      coregulated pilus, was present in thirteen of fourteen isolates (93%) [including
      ten isolates from blood, and three isolates from stool specimens]. CONCLUSIONS:
      Cirrhotic patients with thrombocytopenia were vulnerable to non-O1/non-O139 V.
      cholerae bloodstream invasion. The low prevalence of ctxA and ctxB genes in stool
      specimens indicates other toxins could have contributed to diarrhea. The fact
      that the tcpA gene was highly prevalent in clinical isolates in this study could
      imply an important role of tcpA in the pathogenesis of invasive disease caused by
      non-O1/non-O139 V. cholerae.

PMID- 18087627
TI  - In vitro activity of isepamicin and other aminoglycosides against clinical
      isolates of Gram-negative bacteria causing nosocomial bloodstream infections.
AB  - BACKGROUND AND PURPOSE: Isepamicin is a newly introduced aminoglycoside in
      Taiwan. Since in vitro data for isepamicin against nosocomial Gram-negative
      bloodstream infection from Taiwan are limited, we compared the activity of
      isepamicin, amikacin, gentamicin and tobramycin against nosocomial Gram-negative
      blood isolates. METHODS: A total of 247 non-duplicate nosocomial blood isolates
      of Gram-negative bacteria collected between January 2003 and December 2003 in a
      major teaching hospital in Taiwan were tested for their in vitro susceptibilities
      to gentamicin, tobramycin, amikacin, and isepamicin using the agar dilution
      method. The isolates included Escherichia coli (31 isolates), Klebsiella
      pneumoniae (31), Enterobacter cloacae (30), Serratia marcescens (31), Morganella
      morganii (21), Citrobacter freundii (10), Pseudomonas aeruginosa (31),
      Acinetobacter baumannii (31), and Stenotrophomonas maltophilia (31). RESULTS:
      Overall, isepamicin had high antibacterial activity against the tested Gram
      negative bacteria. For the 154 Enterobacteriaceae isolates, isepamicin had the
      lowest minimum concentration inhibiting 90% of isolates (MIC90) among the tested
      drugs, while its resistance rate (3.9%) was equal to that of amikacin (3.9%) and
      lower than those of tobramycin (18.2%) and gentamicin (21.4%). For the 93 of non
      fermentative Gram-negative bacilli isolates, isepamicin had the lowest MIC90, and
      a resistance rate (23.7%) lower than those of amikacin (27.9%), tobramycin
      (38.7%) and gentamicin (40.9%). CONCLUSIONS: The in vitro activity of isepamicin
      against Gram-negative bacteria isolates was equal or similar to amikacin and
      superior to other tested aminoglycosides. In view of its potential for less
      nephrotoxicity and ototoxicity than other aminoglycosides, isepamicin is a drug
      of choice for the empirical treatment of nosocomial infections caused by Gram
      negative bacteria.

PMID- 18087628
TI  - Clinical manifestations of actinomycosis in Southern Taiwan.
AB  - BACKGROUND AND PURPOSE: Actinomycosis is an uncommon and frequently misdiagnosed
      infection that may present as an acute or indolent process. Even when clinical
      suspicion is high, the disease is commonly confused with other chronic
      inflammatory diseases and malignancy. An early diagnosis helps the clinician in
      deciding treatment and can avoid physical morbidity such as unwarranted surgery.
      METHODS: We retrospectively evaluated the histopathology and selected clinical
      information on all cases of actinomycosis that occurred at Kaohsiung Veterans
      General Hospital in Taiwan from 1993 to 2005. Data on the demographic
      characteristics, predisposing conditions, clinical presentations, diagnosis and
      treatment were analyzed. RESULTS: A total 36 cases of actinomycosis were
      identified and evaluated. The mean age of patients was 52.14 +/- 13.28 years, and
      the male-to-female ratio was 1:1.1. Only three types of actinomycosis were found
      in this study: cervicofacial, at an incidence of 31%; thoracic (33%); and pelvic
      (36%). The clinical manifestations depended upon the region of infection; the
      most frequent presentations of cervicofacial, thoracic and pelvic actinomycosis
      were cutaneous soft tissue swelling with drainage sinus formation (55%),
      hemotypsis (75%) and abnormal vaginal spotting (54%), respectively. The most
      common initial laboratory abnormalities were normochromic anemia (69%) and
      leukocytosis (25%). While most patients had no history of a foreign body, all
      pelvic actinomycotic patients had a history of intrauterine device use. Nineteen
      patients (53%) had no comorbid conditions and 11 patients (31%) had malignancy.
      Most patients were initially diagnosed as malignancy (56%). All patients with
      actinomycosis were diagnosed by histopathologic findings. Twenty two patients
      (61%) were treated by surgery combined with antibiotics, 11 patients (31%) by
      surgery only and 3 patients (8%) by antibiotics only. No recurrence or mortality
      occurred. CONCLUSIONS: Actinomycosis should be included in the differential
      diagnosis when patients present with chronic drainage sinus, chronic hemoptysis
      and abnormal vaginal spotting with use of intrauterine devices.

PMID- 18087629
TI  - Tuberculous arthritis--a fourteen-year experience at a tertiary teaching hospital
      in Taiwan.
AB  - BACKGROUND AND PURPOSE: To characterize the clinical and microbiological features
      of tuberculous arthritis and to clarify the factors affecting treatment outcome.
      METHODS: We retrospectively reviewed 51 adult patients with a diagnosis of
      tuberculous arthritis at Chang Gung Memorial Hospital-Linkou over a 14-year
      period. RESULTS: There were 35 males and 16 females with a mean age of 58.9 years
      (range, 32 to 89 years). The mean duration of symptoms and signs before diagnosis
      was 25.4 months (range, 0.25 to 180 months). Joint pain (96.1%) and swelling
      (90.2%) were two major presentations. Forty five (88.2%) patients had
      monoarthritis. Knee (26.7%) was the most frequently involved one. Twenty six
      (51.0%) patients had roentgenologic evidence of pulmonary tuberculosis (TB).
      Forty three patients (84.3%) had positive TB culture of synovial fluid and/or
      tissue. Of which, 27 (63%) had positive acid-fast bacillus smear. Twenty five
      patients had sputum for mycobacterial smear and culture, and 17 of them had
      positive TB culture. Thirty six patients received post-treatment follow-up for 3
      to 110 months. Among them, 8 had relapses and 28 had treatment success. Compared
      the relapse to the success, the former had a higher ratio of drug resistant
      strains (odds ratio, 7.8; 95% confidence interval, 1.025-59.337; p=0.047) and had
      a longer treatment duration (22.0 +/- 4.4 vs 13.2 +/- 4.1 months; p=0.001).
      CONCLUSIONS: Tuberculous arthritis often occurred in elderly people with male
      predominance. Drug resistant strain may cause a relapse of tuberculous arthritis,
      which may result in longer treatment duration. Routine chest X-ray and sputum for
      mycobacterial smear and culture could be necessary to find concurrent pulmonary
      TB.

PMID- 18087630
TI  - Fournier's gangrene: ten-year experience in a medical center in northern Taiwan.
AB  - BACKGROUND AND PURPOSE: Fournier's gangrene is a life-threatening infection. The
      mortality is still high despite the rapid advancement of modern intensive care
      and surgical technique. In this study, we present our institution's recent
      experience with a large series of patients with Fournier's gangrene. METHODS: A
      retrospective chart review was performed including 44 consecutive patients with
      Fournier's gangrene over a 10-year period. RESULTS: The 44 cases comprised 39
      males and 5 females, with a mean age of 55.5 years. The mean duration of
      hospitalization was 27.9 days. Overall mortality was 22.7%. Diabetes mellitus,
      hypertension, chronic liver disease, liver cirrhosis and chronic renal
      insufficiency were the 5 leading predisposing factors. Liver cirrhosis was highly
      related to mortality (p=0.009). The etiologic origin of the gangrene was
      colorectal, urological and dermatological in 52.3%, 25.0%, and 11.4% of patients,
      respectively. The most common isolated pathogens were Escherichia coli,
      Bacteroides fragilis, Klebsiella pneumoniae, Enterococcus spp., and Proteus
      mirabilis. There were a total of 74 debridements. Other related surgical
      procedures were reconstruction surgery (n = 18), colostomy (2), cystostomy (1),
      vasectomy (1), orchiectomy (1) and penectomy (1). Major complications of
      Fournier's gangrene, including respiratory failure, renal failure, septic shock,
      hepatic failure and disseminated intravascular coagulopathy, were significantly
      to mortality (p<0.05). CONCLUSIONS: Early diagnosis, intensive medical care
      (aggressive resuscitation and broad-spectrum antibiotics), and prompt and
      repeated surgical intervention are the mainstays of treatment. Liver cirrhosis in
      particular is a poor prognostic factor. Reconstructive surgery should also be a
      consideration once the acute condition has improved. Patients with comorbid
      condition, serious infection, and major complications should be treated carefully
      and aggressively.

PMID- 18087631
TI  - Rapid diagnosis of Mycoplasma pneumoniae infection in children by polymerase
      chain reaction.
AB  - BACKGROUND AND PURPOSE: Endemic atypical pneumonia was noted in central Taiwan
      during 2005. The serological response to Mycoplasma pneumoniae infection was
      usually poor in its early course; convalescent serum was needed in most cases,
      which was sometimes difficult to obtain in children. Empiric antimicrobial
      therapy was usually initiated before serological testing. A rapid test would be
      useful to define the etiology and initiate appropriate management. We studied the
      usefulness of polymerase chain reaction (PCR) analysis for diagnosis in this
      setting. METHODS: This 1-year prospective study conducted during 2005 in central
      Taiwan enrolled 307 hospitalized children (aged 3 months to 16 years) with
      respiratory tract infections, some complicated with systemic manifestations, such
      as encephalitis and skin rash. Fifty one patients were excluded due to
      unavailability of data or lack of consent. PCR analysis of samples using a primer
      set for the P1 gene of M. pneumoniae was compared to serological testing,
      including particle agglutinin test and enzyme-linked immunosorbent assay.
      RESULTS: 263 throat swabs from 256 patients were available for PCR tests, and
      serological tests were performed in 140 children (55%) with clinical suspicion of
      atypical pneumonia. Eighty two children (32%) were positive by the PCR method and
      76 (30%) were serologically positive. Seventy one patients (87%) with duration of
      disease onset of 2 to 7 days had positive PCR results. The mean age of patients
      with M. pneumoniae infection was 5.2 years, with 27% of patients <2 years old and
      73% of patients >2 years of age. The diagnoses were as follows: pneumonia (n =
      44); pneumonia complicated with pleural effusion (n = 12); bronchitis and
      bronchopneumonia (n = 18); asthmatic bronchitis (n = 2); croup syndrome (n = 1);
      pharyngitis (n = 3); and herpangina (n = 2). Coinfection with bacteria or virus
      was found in 21% of patients with M. pneumoniae infection. CONCLUSIONS: The PCR
      method could provide earlier diagnosis of M. pneumoniae infection and was useful
      to identify variable clinical features of infection, especially in younger
      children.

PMID- 18087632
TI  - Clinical differentiation of acute pyelonephritis from lower urinary tract
      infection in children.
AB  - BACKGROUND AND PURPOSE: To evaluate clinical variables for diagnosing childhood
      acute pyelonephritis (APN) when technetium-99m dimercaptosuccinic acid (DMSA)
      scintigraphy is not available. METHODS: We retrospectively reviewed the records
      of 590 children with febrile UTI seen from January 1999 to February 2004. On the
      basis of DMSA scintigraphy performed within 7 days after admission, they were
      divided into APN (n = 237) or non-APN (n = 353) groups. Gender, age, clinical
      presentation, absolute neutrophil count, C-reactive protein (CRP), urinalysis,
      culture, and sonographic findings were recorded from charts. RESULTS: A CRP level
      of > or =66.4 mg/L, in patients with >2 days prior to admission had a sensitivity
      of 71.6% and a specificity of 72.5% for APN. Similarly, a CRP of >27.3 mg/L in
      patients with < or =2 days prior to admission and a white cell count of
      >14,990/mm3 had sensitivities of 68.6% and 62.0% and specificities of 66.1% and
      63.0%, respectively. Combining two or more variables did not result in better
      discrimination. CONCLUSIONS: If a DMSA scan is not available, it is reasonable to
      treat a febrile UTI as APN if the CRP is >66.4 mg/L in a patient with >2 days of
      fever or if the CRP is >27.3 mg/L in a patient febrile for < or =2 days.

PMID- 18087633
TI  - Clinical analysis of computed tomography-staged orbital cellulitis in children.
AB  - BACKGROUND AND PURPOSE: Bacterial infection of the orbital structures can affect
      all age groups, but is more frequent in pediatric populations. Prompt
      recognition, correct diagnosis, and adequate management are important if serious
      complications are to be avoided. This study sought to delineate the clinical,
      bacteriological and radiological findings, management and outcome of orbital
      cellulitis. METHODS: This retrospective study reviewed 80 children admitted to
      Chang Gung Children's Hospital with a diagnosis of orbital cellulitis who were
      staged by computed tomography (CT), between January 1999 and August 2005. The
      staging classification was as follows: stage I, inflammatory edema (preseptal);
      stage II, subperiosteal phlegmon and abscess; stage III, orbital cellulitis;
      stage IV, orbital abscess; and stage V, ophthalmic vein and cavernous sinus
      thrombosis. The patients were categorized into 2 groups: preseptal (stage I) and
      postseptal (stage II-V). RESULTS: Of the 80 children, 50 were male and the mean
      age was 6.8 years. Sinusitis and upper respiratory tract infection were the most
      common predisposing factors. Forty one percent of patients in stage I presented
      with symptoms that indicated postseptal involvement. The patients with postseptal
      involvement had a significantly higher rate of proptosis and limitation of
      extraocular motility. Bacterial pathogens were identified in 31 patients (39%),
      the 2 most common pathogens being Staphylococcus and Streptococcus. Ten patients
      (13%) had polymicrobial infection. Twenty three patients underwent sinus and/or
      orbital and/or intracranial surgery, including all 5 patients (100%) in stage IV,
      3 of 6 patients (50%) in stage III, 13 of 35 patients (37%) in stage II, and 2 of
      34 patients (6%) in stage I. Complete resolution without complication was
      achieved in 72 children. Eight patients had complications, including intracranial
      infection in 3, recollection of abscess in 2, ophthalmoplegia in 2, and corneal
      scar in 1. CONCLUSIONS: Proptosis and limitation of extraocular motility may be
      considered the most important signs on CT examination in children with suspicious
      orbital cellulitis. Given that polymicrobial infection is common, broad-spectrum
      antibiotics are indicated initially. Surgery should be considered not only when
      an abscess is demonstrated by CT scan but also if clinical deterioration occurs
      within 24 to 36 h of adequate intravenous antibiotic treatment.

PMID- 18087634
TI  - Cardiopulmonary involvement in pediatric systemic lupus erythematosus: a twenty
      year retrospective analysis.
AB  - BACKGROUND AND PURPOSE: Cardiovascular and pulmonary involvement is frequent
      among patients with systemic lupus erythematosus (SLE). It is important that the
      frequency and characteristics of pulmonary and cardiovascular involvement in
      childhood-onset SLE are understood. Thus, we conducted a retrospective analysis
      of childhood-onset SLE at a tertiary medical center in Taipei. METHODS: Children
      with SLE diagnosed at the National Taiwan University Hospital between 1985 and
      2004 were evaluated by chart review. Records included the age at diagnosis,
      gender, family history, presenting manifestations with American Rheumatism
      Association criteria and initial laboratory data, other associated complications
      and duration of follow-up. RESULTS: A total of 157 cases were included. The male
      to-female ratio was 18:82, with the mean age at diagnosis 12.2 years. Overall,
      pulmonary and cardiovascular involvements were recorded in 89 patients (56.7%)
      and 75 patients (47.8%), respectively. Among the more frequent lung disorders
      were pneumonia treated under hospitalization (in 36.9% of patients), increased
      pulmonary interstitial marking or infiltration (35.0%), and pleuritis (33.1%).
      The more common cardiovascular manifestations included cardiomegaly (in 33.8%),
      pericarditis (28.7%) and arrhythmia/conduction anomaly (12.7%). CONCLUSIONS: The
      frequencies of pulmonary and cardiovascular complications were high. Blood
      creatinine >1 mg/dL, hematuria and anemia with hemoglobin <12 g/dL obtained at
      diagnosis of SLE were associated with cardiovascular complications during the
      disease course, while anti-double stranded DNA at diagnosis was associated with
      pulmonary complications.

PMID- 18087635
TI  - Physicians' adherence to guidelines for empirical treatment of urinary tract
      infection in Taiwan.
AB  - BACKGROUND AND PURPOSE: Guidelines for prescribing antibiotics for uncomplicated
      urinary tract infection (UTI) were established in Taiwan in 2000. This study
      investigated the extent of physicians' adherence to the guidelines for treating
      ambulatory women with UTI. METHODS: National Health Insurance claims data were
      used to evaluate antibiotic prescription behavior for UTI among physicians
      serving in hospitals across the range of accreditation levels in Taiwan,
      including medical centers, regional hospitals, district teaching/non-teaching
      hospitals and community clinics. A random sample of 5047 female ambulatory care
      visits during 2001 and 2003 was analyzed. RESULTS: Sulfonamides (trimethoprim and
      trimethoprim-sulfamethoxazole), first-generation cephalosporins and quinolones
      were the most commonly prescribed drugs. The overall guideline adherence rate for
      physicians was 72.1%. The differences in guideline adherence rates for physicians
      in medical centers (86.6%), regional hospitals (81.3%), district teaching/non
      teaching hospitals (76.9%) and community clinics (69.5%) were statistically
      significant (chi-squared test; p<0.0001). CONCLUSION: Physicians in community
      clinics were less likely to adhere to guidelines in the treatment of ambulatory
      cases of UTI than physicians in any of the different levels of accredited
      hospitals in Taiwan.

PMID- 18087636
TI  - Successful treatment of meningitis caused by multidrug-resistant Acinetobacter
      baumannii with intravenous and intrathecal colistin.
AB  - Multidrug-resistant Acinetobacter baumannii is an emergent nosocomial pathogen. A
      61-year-old woman developed meningitis caused by MDRAB 27 days after receiving a
      surgical intervention for invasive meningioma. The patient failed to respond to
      high doses of meropenem and sulbactam treatment and the organism persisted in the
      cerebrospinal fluids for two months. The regimen was changed to intravenous and
      intrathecal colistin for 28 days and the patient responded well. Administration
      of colistin both intravenously and intrathecally could be a suitable option as a
      salvage therapy for meningitis due to multidrug-resistant A. baumannii.

PMID- 18087637
TI  - Men's health is evolving.

PMID- 18087639
TI  - Endothelium-specific gene and stem cell-based therapy for erectile dysfunction.
AB  - Erectile dysfunction (ED) commonly results from endothelial dysfunction of the
      systemic vasculature. Although phosphodiesterase type 5 (PDE-5) inhibitors are
      effective at treating most cases of ED, they must be taken routinely and are
      ineffectual for a meaningful number of men. In recent years gene and stem cell
      based therapies targeted at the penile endothelium have been gaining momentum in
      preclinical studies. These early studies reveal that gene and stem cell-based
      therapies may be both enduring and efficacious, and may eventually lead to a cure
      for ED. The following review will highlight our current understanding of
      endothelial-specific gene and stem cell-based therapies performed to date in a
      number of experimental animal models.

PMID- 18087638
TI  - NADPH oxidase: recent evidence for its role in erectile dysfunction.
AB  - Important roles for reactive oxygen species (ROS) in physiology and
      pathophysiology have been increasingly recognized. Under normal conditions, ROS
      serve as signaling molecules in the regulation of cellular functions. However,
      enhanced ROS production as a result of the activation of nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase contributes significantly to the
      pathogeneses of vascular diseases. Although it has become evident that increased
      ROS is associated with erectile dysfunction (ED), the sources of ROS in the penis
      remain largely unknown. In recent years, emergent evidence suggests the possible
      role of NADPH oxidase in inducing ED. In this review, we examine the relationship
      between ROS and ED in different disease models and discuss the current evidence
      basis for NADPH oxidase-derived ROS in ED.

PMID- 18087640
TI  - Growth factors for therapeutic angiogenesis in hypercholesterolemic erectile
      dysfunction.
AB  - The past decade has seen an explosion of new information on the physiology of
      penile erection, and pathophysiology of erectile dysfunction (ED).
      Hypercholesterolemia is a chronic condition that can lead to degeneration in the
      vasculature bed and can result in ED if the penile vasculature is involved.
      Angiogenesis is the growth of new blood vessels from preexisting vasculature.
      Therapeutic angiogenesis seeks to harness the mechanisms of vascular growth to
      treat disorders of inadequate tissue perfusion, such as coronary artery disease
      and ED. There have been tremendous changes in the field of therapeutic
      angiogenesis over the past decade, and there is much promise for the future.
      Initial preclinical work with cytokine growth factor delivery resulted in a great
      deal of enthusiasm for the treatment of ischemic heart and/or peripheral vascular
      disease, though clinical studies have not achieved similar success. With an
      increased understanding of the complex mechanisms involved in angiogenesis, novel
      therapies which target multiple different angiogenic pathways are also being
      developed and tested. The penis is a convenient tissue target for gene therapy
      because of its external location and accessibility, the ubiquity of endothelial
      lined spaces, and low level of blood flow, especially in the flaccid state.
      Therapeutic angiogenesis is an exciting field that continues to evolve. This
      review will focus on the development of growth factors for hypercholesterolemic
      ED, the use of various growth factors for ED therapy, their routes of delivery,
      and the results in animal studies.

PMID- 18087642
TI  - Hypogonadism and erectile dysfunction: an overview.
AB  - In humans androgen decline is presented as a clinical picture which includes
      decreased sexual interest, diminished erectile capacity, delayed or absent
      orgasms and reduced sexual pleasure. Additionally, changes in mood, diminished
      well being, fatigue, depression and irritability are also associated with
      androgen insufficiency. The critical role of androgens on the development,
      growth, and maintenance of the penis has been widely accepted. Although, the
      exact effect of androgens on erectile physiology still remains undetermined,
      recent experimental studies have broaden our understanding about the relationship
      between androgens and erectile function. Preclinical studies showed that androgen
      deprivation leads to penile tissue atrophy and alterations in the nerve
      structures of the penis. Furthermore, androgen deprivation caused to accumulation
      of fat containing cells and decreased protein expression of endothelial and
      neuronal nitric oxide synthases (eNOS and nNOS), and phosphodiesterase type-5
      (PDE-5), which play crucial role in normal erectile physiology. On the light of
      the recent literature, we aimed to present the direct effect of androgens on the
      structures, development and maintenance of penile tissue and erectile physiology
      as well. Furthermore, according to the clinical studies we conclude the
      aetiology, pathophysiology, prevalence, diagnosis and treatment options of
      hypogonadism in aging men.

PMID- 18087641
TI  - Do lifestyle changes work for improving erectile dysfunction?
AB  - The main cause of erectile dysfunction (ED) is organic in nature, with vascular
      etiologies being the most common risk factors. Although there have been
      sufficient data on the relationship between ED and several well-recognized risk
      factors, including aging, coronary artery disease, atherosclerosis, diabetes
      mellitus, dyslipidemia, high blood pressure, and pelvic surgeries, little
      attention has been paid by the urologists to the role of lifestyle factors in ED.
      However, accumulating data from basic science and clinical studies have
      determined a link between the occurrence of ED and a number of lifestyle factors,
      such as smoking, obesity, alcohol consumption, and lack of physical activity. The
      application of findings from animal and human studies to the clinical practice
      regarding the modification of lifestyle factors could help improving ED as well
      as reducing the risks of developing cardiovascular diseases. This communication
      addresses the impact of lifestyle factors on erectile function and the potential
      benefits of modifying these factors to improve ED in respect to the current
      evidence.

PMID- 18087643
TI  - Common approach to managing lower urinary tract symptoms and erectile
      dysfunction.
AB  - The present paper serves as a review of the associations between lower urinary
      tract symptoms (LUTS) and erectile dysfunction (ED), with a focus on common and
      combined pathways for treatment. LUTS and ED are common conditions seen in
      general urologic practice. Research has started to establish epidemiologic and
      pathophysiologic links between the two conditions and a strong association
      confirmed across multiple studies. Men seeking care for one condition should
      always be interviewed for complaints of the other condition. Proposed common
      pathways include alpha-1 adrenergic receptor imbalance, Rho-kinase overactivity,
      endothelial cell dysfunction and atherosclerosis-induced ischemia. Medical
      therapy has replaced surgery as the first-line treatment for LUTS in most
      patients, with the incorporation of alpha-adrenergic receptor antagonists (alpha
      ARAs) and 5-alpha-reductase inhibitors (5-ARIs) into everyday practice. Treatment
      with alpha-ARAs contributes to some improvement in ED, whereas use of 5-ARIs
      results in worsened sexual function in some patients. Phosphodiesterase-5 (PDE-5)
      inhibitors have revolutionized the treatment of ED with a simple oral regimen,
      and new insights demonstrate a benefit of combined use of PDE-5 inhibitors and
      alpha-ARAs. The mechanisms of action of these medications support these observed
      benefits, and they are being studied in the basic science and clinical settings.
      In addition, novel mechanisms for therapy have been proposed based on clinical
      and research observations. The minimally invasive and surgical treatments for
      LUTS are known to have adverse effects on ejaculatory function, while their
      effects on erectile function are still debated. Much remains to be investigated,
      but it is clear that the associations between LUTS and ED lay the foundation for
      future therapies and possible preventative strategies.

PMID- 18087644
TI  - Emerging neuromodulatory molecules for the treatment of neurogenic erectile
      dysfunction caused by cavernous nerve injury.
AB  - Advances in the neurobiology of growth factors, neural development, and
      prevention of cell death have resulted in a heightened clinical interest for the
      development of protective and regenerative neuromodulatory strategies for the
      cavernous nerves (CNs), as therapies for prostate cancer and other pelvic
      malignancies often result in neuronal damage and debilitating loss of sexual
      function. Nitric oxide released from the axonal end plates of these nerves within
      the corpora cavernosa causes relaxation of smooth muscle, initiating the
      haemodynamic changes of penile erection as well as contributing to maintained
      tumescence; the loss of CN function is primarily responsible for the development
      of erectile dysfunction (ED) after pelvic surgery and serves as the primary
      target for potential neuroprotective or regenerative strategies. Evidence from
      pre-clinical studies for select neuromodulatory approaches is reviewed, including
      neurotrophins, glial cell line-derived neurotrophic factors (GDNF), bone
      morphogenic proteins, immunophilin ligands, erythropoetin (EPO), and stem cells.

PMID- 18087645
TI  - Rehabilitation of erectile function following radical prostatectomy.
AB  - The concept of muscle rehabilitation after nerve injury is not a novel idea and
      is practiced in many branches of medicine, including urology. Bladder
      rehabilitation after spinal cord injury is universally practiced. The erectile
      dysfunction (ED) experienced after radical prostatectomy (RP) is increasingly
      recognized as being primarily neurogenic followed by secondary penile smooth
      muscle (SM) changes. There is unfortunately no standard approach to penile
      rehabilitation after RP because controlled prospective human studies are not
      available. This article reviews the epidemiology, experimental pathophysiological
      models, rationale for penile rehabilitation, and currently published
      rehabilitation strategies.

PMID- 18087646
TI  - Erectile function after urethral reconstruction.
AB  - Advances in urogenital plastic surgical tissue transfer techniques have enabled
      urethral reconstruction surgery to become the new gold-standard for treatment of
      refractory urethral stricture disease. Questions remain, however, regarding the
      long-term implications on sexual function after major genital reconstructive
      surgery. In this article, we review the pathologic features of urethral stricture
      disease and urologic trauma that may affect erectile function (EF) and assess the
      impact of various specific contemporary urethroplasty surgical techniques on male
      sexual function.

PMID- 18087647
TI  - Non-surgical therapy of Peyronie's disease.
AB  - The present paper provides a review of the available non-surgical treatments for
      Peyronie's disease (PD). A review of published literature on oral, intralesional,
      external energy and iontophoresis therapies for PD was performed, and the
      published results of available treatment options reviewed. The authors
      recommendations for appropriate non-surgical management of PD are provided.
      Although there are many published reports that show the efficacy of non-surgical
      therapies for PD, there is a lack of large scale, multicenter controlled clinical
      trials, which makes treatment recommendations difficult. Careful review of the
      literature does suggest that there are treatment options that make scientific
      sense and appear to stabilize the disease process, reduce deformity, and improve
      function. Offering no treatment at all will encourage our patients to pursue
      alternative treatments, which might do harm, and misses the opportunity to do
      some good. Clearly further work is necessary to develop safe and effective non
      surgical treatments for PD.

PMID- 18087648
TI  - Insights of priapism mechanism and rationale treatment for recurrent priapism.
AB  - Priapism is defined as abnormal prolonged penile erection occurring beyond or
      unrelated to sexual interest. The disorder is enigmatic yet devastating because
      of its elusive etiology, irreversible erectile tissue damage, and resultant
      erectile dysfunction (ED). Current management strategies suffer from a poor
      understanding of the pathophysiology, especially at the molecular level. The
      traditional treatments are based more on empirical rather than evidence-based
      knowledge. The outcomes for restoration of normal erectile function are poor,
      especially for stuttering priapism. Therefore, it is critical to understand
      priapism from a molecular level, to formulate treatment strategies and to
      establish rational prevention strategies for high-risk populations, such as
      sickle cell disease (SCD) patients and cases of the stuttering variant. This
      review focuses on the recent advances at the molecular level in priapism and
      penile erection, and applies the recent knowledge to the treatment of stuttering
      priapism.

PMID- 18087649
TI  - Premature ejaculation: current and future treatments.
AB  - Premature ejaculation (PE) is recognized to be the most common male sexual
      disorder. PE provides difficulties for professionals who treat this condition
      because there is neither a universally accepted definition nor a medication
      approved by the Food and Drug Administration (FDA). Despite these shortcomings,
      physicians continue to diagnose their patients with PE according to major
      guidelines and treat them with either behavioral therapies or off-label
      medications. This review focuses on current and emerging treatment options and
      medications for PE. Advantages and limitations of each treatment option are
      discussed in the light of current published peer-reviewed literature.

PMID- 18087650
TI  - Global epidemiology of sexually transmitted diseases.
AB  - Sexually transmitted diseases (STDs) are among the first ten causes of unpleasant
      diseases in young adult males in developing countries and the second major cause
      of unpleasant diseases in young adult women. Adolescents and young adults (15-24
      years old) make up only 25% of the sexually active population, but represent
      almost 50% of all new acquired STDs. In general, STDs are epidemics and present
      an enormous health and economic consequences. An adequate screening for STDs
      should be done on a routine basis in every part of the world. Many STDs are
      asymptomatic and therefore can difficult to control. The purpose of reporting of
      STDs is to ensure that persons who are infected will be quickly diagnosed and
      appropriately treated to control the spread of infection and also so that
      partners are notified, tested and appropriately treated. It is estimated that
      reported cases of STDs represent only 50%-80% of reportable STD infections in the
      United States, reflecting limited screening and low disease reporting. High-risk
      sexual behavior is a highly contributive factor of this process as it often leads
      to teenage pregnancies and HIV/AIDS. One possible explanation for this behavior
      is that people do not have enough information about the transmission of STDs or
      ignore the precautions required for safe sex. Approximately 60% of new HIV
      infections worldwide occur in young people. The frequency of high-risk behaviors
      among youths may also be influenced by opportunity to engage in them,
      particularly the amount of time that they are unsupervised by adults. However, in
      diagnosing and treating these patients, we can effectively prevent the spread of
      HIV/AIDS. Individuals infected with STDs are 5-10 times more likely than
      uninfected individuals to acquire or transmit HIV through sexual contact. The
      breaking of the genital tract lining or skin creates a portal of entry for HIV
      and, hence, HIV-infected individuals with other STDs are more likely to shed HIV
      in their genital secretions. To date, the condom is the most effective method
      available for males for protection against STDs. It is important to control STDs,
      and prevention can be the key of this process. Prevention can be achieved through
      education of the population, identification of symptomatic and asymptomatic
      people, and effective diagnosis and treatment of these patients and their
      partners.

PMID- 18087651
TI  - Effects of phosphodiesterase-5 inhibitors on sperm parameters and fertilizing
      capacity.
AB  - The aim of this review study is to elucidate the effects that phosphodiesterase 5
      (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on
      their ability to fertilize the oocyte. Second messenger systems such as the
      cAMP/adenylate cyclase (AC) system and the cGMP/guanylate cyclase (GC) system
      appear to regulate sperm functions. Increased levels of intracytosolic cAMP
      result in an enhancement of sperm motility and viability. The stimulation of GC
      by low doses of nitric oxide (NO) leads to an improvement or maintenance of sperm
      motility, whereas higher concentrations have an adverse effect on sperm
      parameters. Several in vivo and in vitro studies have been carried out in order
      to examine whether PDE5 inhibitors affect positively or negatively sperm
      parameters and sperm fertilizing capacity. The results of these studies are
      controversial. Some of these studies demonstrate no significant effects of PDE5
      inhibitors on the motility, viability, and morphology of spermatozoa collected
      from men that have been treated with PDE5 inhibitors. On the other hand, several
      studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both
      in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a
      stimulatory effect on sperm motility with an increase in intracellular cAMP
      suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than
      the PDE5. On the other hand, tadalafil's actions appear to be associated with the
      inhibitory effect of this compound on PDE11. In vivo studies in men treated with
      vardenafil in a daily basis demonstrated a significantly larger total number of
      spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm
      motility; it has been suggested that vardenafil administration enhances the
      secretory function of the prostate and subsequently increases the qualitative and
      quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on
      sperm parameters may lead to the improvement of the outcome of assisted
      reproductive technology (ART) programs. In the future PDE5 inhibitors might serve
      as adjunct therapeutical agents for the alleviation of male infertility.

PMID- 18087652
TI  - Endocrine disruptors and estrogenic effects on male reproductive axis.
AB  - Endocrine disruptors (e.g., polychlorinated biphenyls [PCBs], dichlorodiphenyl
      trichloroethane [DDT], dioxin, and some pesticides) are estrogen-like and anti
      androgenic chemicals in the environment. They mimic natural hormones, inhibit the
      action of hormones, or alter the normal regulatory function of the endocrine
      system and have potential hazardous effects on male reproductive axis causing
      infertility. Although testicular and prostate cancers, abnormal sexual
      development, undescended testis, chronic inflammation, Sertoli-cell-only pattern,
      hypospadias, altered pituitary and thyroid gland functions are also observed, the
      available data are insufficient to deduce worldwide conclusions. The development
      of intra-cytoplasmic sperm injection (ICSI) is beyond doubt the most important
      recent breakthrough in the treatment of male infertility, but it does not
      necessarily treat the cause and may inadvertently pass on adverse genetic
      consequences. Many well-controlled clinical studies and basic scientific
      discoveries in the physiology, biochemistry, and molecular and cellular biology
      of the male reproductive system have helped in the identification of greater
      numbers of men with male factor problems. Newer tools for the detection of Y
      chromosome deletions have further strengthened the hypothesis that the decline in
      male reproductive health and fertility may be related to the presence of certain
      toxic chemicals in the environment. Thus the etiology, diagnosis, and treatment
      of male factor infertility remain a real challenge. Clinicians should always
      attempt to identify the etiology of a possible testicular toxicity, assess the
      degree of risk to the patient being evaluated for infertility, and initiate a
      plan to control and prevent exposure to others once an association between
      occupation/toxicant and infertility has been established.

PMID- 18087653
TI  - Initial experience with robot-assisted varicocelectomy.
AB  - AIM: To determine if robot-assisted varicocelectomy can be safely and effectively
      performed when compared to microscopic inguinal varicocelectomy. METHODS: Eight
      patients aged 29.1+/-12.5 years underwent microscopic subinguinal
      varicocelectomies: seven patients with left-sided repair, and one patient with
      bilateral repair. Eight patients aged 22.0+/-8.0 years underwent robot-assisted
      varicocelectomies: seven patients with left-sided repair and one patient with
      bilateral repair. RESULTS: The average operative time for microscopic inguinal
      varicocelectomy was 73.9+/-12.2 min, whereas the robot-assisted technique took
      71.1+/-21.1 min. There were no difficulties in identifying and isolating vessels
      and the vas deferens with robot-assisted subinguinal varicocelectomy. Hand tremor
      was eliminated using the robotic procedure. Patients who underwent either
      microscopic or robot-assisted varicocelectomies were able to resume daily
      activities on the day of surgery and full activities within 2 weeks. There were
      no complications or recurrences of varicocele. CONCLUSION: From our experience,
      compared to microscopic surgery, robot-assisted varicocelectomy can be safely and
      effectively performed, with the added benefit of eliminating hand tremor.

PMID- 18087654
TI  - Combination therapy for male erectile dysfunction and urinary incontinence.
AB  - Urinary incontinence (UI) and erectile dysfunction (ED) are both very prevalent
      conditions. Insertion of an artificial urinary sphincter (AUS) and penile
      prosthesis (PP) is an effective and proven method of treatment for both
      conditions. With advancing age, as well as with increasing populations of
      patients radically treated for prostate cancer, the occurrence of both conditions
      found in the same patient is increasing. The purpose of this article was to
      analyze the available evidence for simultaneous surgical management of male ED
      and UI using prosthetic devices. The existing literature pertaining to dual
      implantation of AUS and PP was reviewed. The concomitant insertion of the PP with
      the male perineal sling was also considered. Concurrent ED and UI are
      increasingly seen in the post radical prostatectomy population, who are often
      younger and less willing to suffer with these conditions. Insertion of an AUS and
      PP, either simultaneously or as a two-stage procedure, appears to be a safe,
      efficacious and long-lasting method of treatment. The improvements in design of
      both the AUS and PP as well as the development of the single transverse scrotal
      incision have made simultaneous insertion of these prostheses possible. Dual
      implantation of the PP and male sling looks promising in a selected population.
      In conclusion, the insertion of the AUS and PP for the treatment of concurrent UI
      and ED is safe and effective. Simultaneous insertion of these prostheses in the
      same patient offers potential advantages in operative and recovery time and is
      associated with high patient satisfaction. Combination therapy should therefore
      be included in the arsenal of treatment of these conditions.

PMID- 18087655
TI  - Ventral phalloplasty.
AB  - AIM: To present a simple technique during penile prosthesis implantation that
      promotes the perception of increased phallic length. METHODS: The penoscrotal web
      is defined. A "check mark" incision is made with excision of scrotal tissue.
      Excellent exposure is provided for implantation of the cylinders, pump and
      reservoir. Wound closure is performed longitudinally. RESULTS: This technique is
      a modified extension of surgeries described in the pediatric literature for
      webbed penis. Loss of penile length following penile implantation surgery is
      worrisome for patients suffering from erectile dysfunction (ED). This technique
      helps with patient satisfaction, cosmetic results, and improves perception of
      penile length. CONCLUSION: Ventral phalloplasty is a safe, technically simple
      procedure that may be performed in concert with penile prosthesis implantation or
      as a stand alone procedure under certain circumstances.

PMID- 18087656
TI  - Surgical treatment of Peyronie's disease: choosing the best approach to improve
      patient satisfaction.
AB  - AIM: To discuss important points on medical history, preoperative evaluation,
      real expectations, and selection of the appropriate surgical procedure to improve
      patient satisfaction after surgical procedures for Peyronie's disease. METHODS:
      Recent advances in approaches to Peyronie's disease are discussed based on the
      literature and personal experiences. Issues concerning surgical indication,
      patient selection, surgical techniques, and grafting are discussed. Lengthening
      procedures on the convex side of the penile curvature by means of grafting offer
      the best possible gain from a reconstruction standpoint. Penile rectification and
      rigidity are required to achieve a completely functional penis. Most patients
      experience associated erectile dysfunction (ED), and penile straightening alone
      may not be enough to restore complete function. Twenty-five patients were
      submitted to total penile reconstruction on length and girth with concomitant
      penile prosthesis implant. The maximum length restoration was possible and
      limited by the length of the dissected neurovascular bundle. The mean age was
      55.4 years (32-69 years) and the mean angle of curvature 74.2+/-22.4 degree (0
      100 degree). Pericardial grafting was used to cover the defect. The mean follow
      up time was 11.2 +/- 5.9 months (3-22 months). RESULTS: Mean functional penile
      length gain was 3.40+/-0.73 cm (2-5 cm). Penile prosthesis maintained the penis
      straight. No infections occurred. Sexual intercourse was restored in all patients
      and all reported recovered self-esteem. CONCLUSION: Improving patient
      satisfaction with the surgical treatment includes proper preoperative evaluation
      on stable disease, penile shortening, vascular and erectile status, patient
      decision and selection as well as extensive discussion on surgical technique for
      restoring functional penis (length and rigidity). Length and girth restoration is
      very important for self-esteem and patient satisfaction.

PMID- 18087657
TI  - The dermatology dispensing debate.
AB  - The in-office dispensing of topical skin care products by dermatologists is a
      source of frequent debate. Guidelines for proper dispensing have been penned by
      various medical organizations, yet the controversy continues. With the increasing
      number of physician-dispensed lines available for sale, combined with mounting
      medical financial issues, the ongoing debate surrounding in-office dispensing
      will continue.

PMID- 18087658
TI  - Treatment of hand and foot psoriasis with emphasis on efalizumab.
AB  - Hand and foot psoriasis is a chronic and debilitating disease that manifests as
      plaque-type or pustular-type lesions. Although the palms and soles represent only
      2% of the total body surface area, psoriasis of these regions may lead to
      physical dysfunctions that can greatly impair dexterity, mobility, and the
      quality of life of affected individuals. Deregulation of T-lymphocyte-mediated
      immune response is important in the pathophysiology of psoriasis. Efalizumab
      (Raptiva, Genentech) is an anti-CD11a monoclonal antibody that disrupts the
      interaction between T cells and antigen-presenting cells, thereby inhibiting
      various T-cell-mediated immune processes that include activation and trafficking.
      Recent evidence indicates that efalizumab may be beneficial for patients with
      hand and foot psoriasis.

PMID- 18087659
TI  - Trend of hip fracture incidence in Germany 1995-2004: a population-based study.
AB  - We analyzed hip fracture incidence trends in Germany 1995-2004, using national
      hospital discharge register. Crude incidences per 100,000 increased from 121.2
      (95% CI 120.5-121.9) in 1995 to 140.9 (140.2-141.7) in 2004. Age-sex-adjusted
      annual incidence ratios showed a statistically significant, but only slight
      increase (1.01, p<0.01), compared to higher rises in the past. Trends differed
      markedly with sex, age, and regions. INTRODUCTION: Data concerning actual trends
      of the hip fracture incidence and differences for sex, age, and region are
      limited. We analyzed hip fracture incidence trends in Germany 1995-2004, using
      the national hospital discharge register. Crude incidences per 100,000 increased
      from 121.2 (95% CI 120.5-121.9) in 1995 to 140.9 (140.2-141.7) in 2004. Age-sex
      adjusted annual incidence ratios showed a statistically significant, but only
      slight increase (1.01, p<0.01), compared to higher rises in the past. Trends
      differed markedly with sex, age, and regions. METHODS: Analysis of annual hip
      fracture incidences using the national hospital discharge register. Estimate of
      age-sex-adjusted changes was found by using Poisson regression (incidence rate
      ratios, IRR). RESULTS: The number of patients with at least one hospital
      admission for hip fracture increased (1995: n=99,141; 2004: n=116,281). Crude
      incidences per 100,000 were 121.2 (95% confidence interval 120.5-121,9) and 140.9
      (140.2-141.7), respectively. The age-sex-adjusted hip fracture incidence
      increased statistically significantly, but only slightly (IRR per year: 1.01;
      1.00-1.01; IRR 1995-2004: 1.05, p<0.01). In men aged 40 years or older,
      incidences increased. In women, there was a tendency of a decrease up to 74 years
      of age, but also a significant increase in higher age groups. In people 0-39
      years, the incidence declined markedly (IRR 1995-2004, men 0.74; 0.69-0.79, women
      0.62; 0.55-0.69, both p<0.01). The increase was significantly higher in Eastern
      compared to Western Germany (interaction: p=0.002), and differences between East
      and West decreased. CONCLUSIONS: In contrast to earlier years, the hip fracture
      incidence in Germany 1995-2004 increased only slightly, with a decline in younger
      people, but increases in older ages, particularly in men. Regional differences
      decreased.

PMID- 18087660
TI  - Monthly dosing of 75 mg risedronate on 2 consecutive days a month: efficacy and
      safety results.
AB  - Postmenopausal women with osteoporosis received 75 mg risedronate on two
      consecutive days each month or 5 mg daily for 12 months. Changes in bone mineral
      density and bone turnover markers were similar between treatments. Risedronate 75
      mg twice monthly was effective and safe suggesting a new, convenient dosing
      schedule. INTRODUCTION: Patients perceive less frequent dosing as being more
      convenient. This 2-year trial evaluates the efficacy and safety of a new monthly
      oral regimen of risedronate; 1 year results are presented here. METHODS:
      Postmenopausal women with osteoporosis (n = 1229) were randomly assigned to
      double-blind treatment with 75 mg risedronate on two consecutive days each month
      (2CDM), or 5 mg daily. The primary endpoint was the percent change from baseline
      in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary efficacy
      was evaluated by mean percent changes from baseline in BMD in LS, total hip,
      trochanter, and femoral neck, and bone turnover markers (BTMs). RESULTS:
      Risedronate 75 mg 2CDM was non-inferior to 5 mg daily (treatment difference 0.21;
      95% CI -0.19 to 0.62). Mean percent change in LS-BMD was 3.4% +/- 0.16 and 3.6%
      +/- 0.15 respectively. Mean percent changes in BMD and BTMs were significant and
      similar for both treatment groups. New vertebral fractures occurred in 1% of
      subjects with either treatment. Both treatments were generally well tolerated and
      safe. CONCLUSIONS: Risedronate 75 mg 2CDM was non-inferior in efficacy and did
      not show a difference in safety vs. 5 mg daily after 12 months, leading to a
      similar benefit.

PMID- 18087662
TI  - Use of Kirschner wires as endoscopic retractors.

PMID- 18087661
TI  - Compensatory evolution of a WW domain variant lacking the strictly conserved Trp
      residue.
AB  - Replacement of conserved amino acid residues during evolution of proteins can
      lead to divergence and the formation of new families with novel functions, but is
      often deleterious to both protein structure and function. Using the WW domain, we
      experimentally examined whether and to what degree second-site mutations can
      compensate for the reduction of function and loss of structure that accompany
      substitution of a strictly conserved amino acid residue. The W17F mutant of the
      WW domain, with substitution of the most strictly conserved Trp residue, is known
      to lack a specific three-dimensional structure and shows reduced binding affinity
      in comparison to the wild type. To obtain second-site revertants, we performed a
      selection experiment based on the proline-rich peptide (PY ligand) binding
      affinity using the W17F mutant as the initial sequence. After selection by
      ribosome display, we were able to select revertants that exhibited a maximum
      ninefold higher affinity to the PY ligand than the W17F mutant and showed an even
      better affinity than the wild type. In addition, we found that the functional
      restoration resulted in increased binding specificity in selected revertants, and
      the structures were more compact, with increased amounts of secondary structure,
      in comparison to the W17F mutant. Our results suggest that the defective
      structure and function of the proteins caused by mutations in highly conserved
      residues occurring through divergent evolution not only can be restored but can
      be further improved by compensatory mutations.

PMID- 18087663
TI  - Transforming growth factor-beta1-antisense modulates the expression of hepatocyte
      growth factor/scatter factor in keloid fibroblast cell culture.
AB  - Abnormal wound healing processes can result in hypertrophic scars and keloids.
      Transforming growth factor-beta1 (TGF-beta1) and hepatocyte growth factor/scatter
      factor (HGF/SF) are biphasic growth factor cytokines in physiologic and
      pathophysiologic conditions. Findings have shown TGF-beta1 to be pivotal in the
      formation of keloid tissue. Therefore, neutralizing antibodies may allow wound
      healing without keloid formation. As reported, TGF-beta1 is antagonized by
      HGF/SF. Some authors have reported that exogenous administration of HGF/SF
      prevented scar formation. Hence, this study targeted TGF-beta1 and determined the
      levels of HGF/SF in fibroblast cell culture. Keloid tissue was taken from seven
      patients. Another seven patients with mature nonhypertrophic scar served as
      controls. All tissues were cultured, and fibroblast cultures were used for
      further experiments. The TGF-beta1 antisense was administered at 3 and 6
      micromol/ml, and HGF/SF levels were determined after 16, 24, and 48 h of
      incubation. The levels of HGF/SF showed significant differences after incubation
      with antisense oligonucleotides. The increasing antisense levels resulted in
      increased HGF/SF levels (up to 87.66 pg/ml after 48 h of incubation). In
      conclusion, targeting TGF-beta1 resulted in significantly increased levels of
      HGF/SF. The clinical relevance could include the use of locally administered
      HGF/SF in protein or gene form to minimize formation of keloids. Nevertheless,
      wound healing is the result of many interacting cytokines, so neutralizing or
      targeting one protein could result in no significant effect.

PMID- 18087664
TI  - Anatomy and biomechanics of the vertebral aponeurosis part of the posterior layer
      of the thoracolumbar fascia.
AB  - There is significant paucity in the literature regarding vertebral aponeurosis.
      We were able to find only a few descriptions of this specific fascia in the
      extant medical literature. To elucidate further the anatomy of this structure,
      forty adult human cadavers were dissected. Both quantitation and anatomical
      observations were made of the vertebral aponeurosis. The vertebral aponeurosis
      was identified in 100% of specimens. This fascia was identified as a thin fibrous
      layer consisting of longitudinal and transverse connective tissue fibers blended
      together deep to the latissimus dorsi muscle. It attached medially to the spinous
      processes of the of the thoracic vertebrae; laterally to the angles of ribs;
      inferiorly to the fascia covering the serratus posterior inferior muscle
      (superficial lamina of the posterior layer of thoracolumbar fascia); superiorly
      it ran deep to the serratus posterior superior and splenius capitis muscles to
      blend with the deep fascia of the neck. At the level of the serratus posterior
      inferior muscle, the vertebral aponeurosis fused to form a continuous layer
      descending toward the sacrotuberous ligament covering the erector spinae muscle.
      Morphometrically, the mean length of the vertebral aponeurosis was 38 cm and the
      mean width was 24 cm. The mean thickness was three mm. There was no significant
      difference between left and right sides, gender or age with regard to vertebral
      aponeurosis length, width, or thickness (P > 0.05). During manual tension of the
      vertebral aponeurosis, the tensile force necessary for failure had a mean of 38.7
      N. In all specimens, the vertebral aponeurosis was capable of holding sutures
      placed through its substance. We hope that these data will be of use for
      descriptive purposes and may potentially add to our understanding of the
      biomechanics involved in movements of the back. As back pain is perhaps the most
      common reason patients visit their physicians, additional knowledge of this
      anatomical region is important.

PMID- 18087665
TI  - Short- and long-term effects of a novel paclitaxel coated stent in the porcine
      coronary model.
AB  - BACKGROUND: Drug eluting stents (DES) are unique in allowing sustained release
      for weeks after a single short intervention. The challenge with DES still
      remaining is the combination of a biocompatible drug-eluting matrix including an
      antiproliferative drug showing efficacy and safety in restenosis prevention. The
      aim of the present animal studies was to evaluate the novel paclitaxel coated
      Coroflex. Please stent in the porcine coronary model. METHODS AND RESULTS: Stents
      were implanted into LAD and CX arteries of 49 domestic pigs. After 5 days, 4
      weeks, 3 months, or 6 months, the animals underwent control angiography including
      dissection of the stented coronary arteries for histology. After 5 days, 3 and 6
      months the Coroflex. Please stent was compared with its uncoated counterpart and
      a paclitaxel free but polymer coated version. After 28 days, an additional group
      received the Taxus Express(2) stent. After 5 days, healing with the paclitaxel
      coated stent was comparable to the uncoated bare metal stent as reflected in a
      similar neointimal proliferation. Compared to the Taxus stent, the new Coroflex.
      Please stent showed a similar neointimal proliferation after 4 weeks.
      Inflammatory reaction was comparable among the bare stent and polymer coated
      stent groups. Paclitaxel coating was associated with a slightly increased
      inflammatory reaction with both DES. After 3 and 6 months, all groups showed a
      similar neointimal proliferation and inflammatory reaction. CONCLUSION: The
      present porcine studies demonstrate excellent safety of the new paclitaxel coated
      Coroflex stent in the porcine coronary stent model.

PMID- 18087666
TI  - Effects of pentoxifylline on the vascular response to injury after angioplasty in
      rabbit iliac arteries.
AB  - Pentoxifylline (PTX) inhibits the effects of several cytokines and reduces injury
      related collagen accumulation. The aim of the present study was to investigate
      the effect of PTX on the vascular response to injury. We treated rabbits with PTX
      (100 mg/kg/day) or placebo (saline) subcutaneously from 2 days before angioplasty
      of an iliac artery until euthanasia 7 or 28 days later. At 7 days after injury,
      PTX treatment was associated with a more differentiated (less proliferation, more
      smoothelin-positive) intimal smooth muscle cell phenotype. Furthermore, PTX
      reduced myofibroblast accumulation in adventitia. At 28 days after injury, PTX
      treated rabbits had a 48.5% larger lumen area (P = 0.03) and a 28.1% larger area
      within the external elastic lamina (P = 0.04). There were no significant
      differences between PTX-treated rabbits and the placebo group with regard to
      neointima and media area. Angioplasty induced marked neoadventitial hyperplasia,
      which was reduced by 20.5% (P = 0.01) in the PTX-treated group. Finally, PTX
      reduced collagen density in all three arterial layers. We conclude that PTX
      treatment induces less proliferation within the vessel wall early after
      angioplasty and increases late lumen size after angioplasty by a positive effect
      on vascular remodeling.

PMID- 18087667
TI  - Stem cell factor/c-kit signaling mediated cardiac stem cell migration via
      activation of p38 MAPK.
AB  - OBJECTIVE: It was reported that there are cardiac stem cells (CSCs) in the rat
      heart, and they could reconstitute well-differentiated myocardium that are formed
      by blood-carrying new vessels and myocytes. However, how do the CSCs migrate into
      the peri-infarcted areas after myocardial infarction (MI)? It remains entirely
      unknown about the signal transduction involved in the migration of CSCs. METHODS
      AND RESULTS: Rat heart MI was induced by left coronary artery ligation. Both
      immunohistochemical staining and Western blotting analysis was performed to
      detect the expression of SCF protein, and RT-PCR was conducted for the expression
      of SCF mRNA. Cardiac stem cells were isolated from rat hearts, and a cardiac stem
      cell migration assay was performed using a 48-well chemotaxis chamber system. On
      day 5 after MI in rats, the expression of stem cell factor (SCF) mRNA and protein
      was significantly increased in the peri-infarcted area, which was matched with
      more accumulation of CSCs in the region and improvement of cardiac function,
      which was blocked by p38 MAPK selective inhibitor SB203580. In in vitro
      experiments, SCF induced CSC migration in a concentration-dependent manner, and
      the antibody against SCF receptor (c-kit) blocked the SCF-induced CSC migration.
      Western blot analysis showed that the phosphorylated p38 MAPK (Phospho-p38 MAPK)
      was highly increased in the SCF-treated CSCs, and the inhibition of p38 MAPK
      activity significantly attenuated SCF-induced the migration of CSCs. CONCLUSION:
      It demonstrated that SCF/c-kit signaling may mediate the migration of CSCs via
      activation of p38 MAPK.

PMID- 18087668
TI  - Two polymorphisms of presenilin-2 gene (PSEN2) 5' regulatory region are not
      associated with Alzheimer's disease (AD) in the Polish population.
AB  - Presenilin 2 gene (PSEN2) is one of the causative genes for familial Alzheimer's
      disease. A delA polymorphism located in PSEN2 promoter was proposed to be a risk
      factor for early-onset AD. We examined association between AD and PSEN2
      polymorphisms located in two 5'UTR regions in group of 217 late-onset AD
      patients, 109 mild cognitive impairment patients, and 225 non-demented control
      subjects. No significant differences for genotype and allele distributions of a
      delA and a novel insAC polymorphisms in the studied groups as compared to
      controls were observed. Univariate and multivariate risk estimation shows that
      neither delA, insAC alleles nor the genotypes are risk factors for AD. No
      significant interaction between the APOE4 and PSEN2 polymorphisms was found. A
      bioinformatic analysis showed that delA polymorphism influences binding sites of
      transcription factors involved in the cellular processes related to AD. The rare
      variants identified in exon 3 of the PSEN2 could have a potential influence on
      PSEN2 transcript splicing.

PMID- 18087670
TI  - Euphorbia hirta reverses chronic stress-induced anxiety and mediates its action
      through the GABA(A) receptor benzodiazepine receptor-Cl(-) channel complex.
AB  - Chronic stress is known to result in impairment of learning and memory and
      precipitate several affective disorders including depression and anxiety. Drugs
      of natural origin are known to possess several effects on the central nervous
      system and are emerging as promising alternative therapies. In this context, the
      hydroalcoholic extract of Euphorbia hirta (Eh) was evaluated for anxiolytic
      property in chronically stressed rats subjected to elevated plus maze (EPM) and
      open field test (OFT). Eh treatment (200 mg/kg, p.o.; seven days) showed marked
      anti-anxiety activity in chronic immobilization stress. In contrast, the forced
      swim stress-induced anxiety was only partially decreased by Eh. Co-treatment of
      rats with flumazenil (0.5 mg/kg, i.p.), bicuculline (1 mg/kg, i.p.) or picrotoxin
      (1 mg/kg, i.p.) resulted in a significant reduction of anxiolytic effect of Eh
      indicating that its actions are mediated through GABA(A) receptor-benzodiazepine
      receptor-Cl(-) channel complex. Thus, our studies indicate that Eh is a potential
      anxiolytic drug, which might be beneficial in the treatment of stress-induced
      anxiety disorders.

PMID- 18087669
TI  - Lack of relation between drug-seeking behavior in an addiction model and the
      expression of behavioral sensitization in response to ethanol challenge in mice.
AB  - Drug-induced sensitization has been associated with enhanced self-administration
      and may contribute to addiction. The possible association between sensitization
      and voluntary ethanol consumption using an addiction model was investigated. Mice
      (n = 60) were individually housed with ad libitum access to food and had free
      choice between ethanol (5% and 10%) and water in a four-phase paradigm: free
      choice (12 weeks), withdrawal (2 weeks), re-exposure (2 weeks), and quinine
      adulteration (2 weeks). Control mice (n = 10) had access to water. Mice were
      characterized as addicted (n = 10, ethanol preference without reducing intake
      with adulterated ethanol), heavy (n = 22, ethanol preference but reduced intake
      with adulterated ethanol), and light (n = 21, water preference). Oral ethanol
      then was withdrawn, and 24 h later mice received a 2 g/kg ethanol (i.p.)
      challenge dose or saline, and ambulation was evaluated 10 min later. Half of the
      classified mice received daily 2 g/kg ethanol injections for 14 days, and
      ambulation was assessed 10 min after the last dose. Acute ethanol increased
      ambulation in all groups compared to the control group, and chronic ethanol
      induced sensitization, showing no difference among ethanol-treated mice. The data
      suggest that independent neural mechanisms are responsible for the development of
      addiction and sensitization.

PMID- 18087672
TI  - Isolation and characterization of alkane hydroxylases from a metagenomic library
      of Pacific deep-sea sediment.
AB  - Two clones 9E7 and 21G8 in a metagenomic library of the east Pacific deep-sea
      sediment were found to contain alkane hydroxylase genes (alkB). The whole insert
      sequences of the two cosmid clones were determined. The insert sequences of 9E7
      and 21G8 are 40 and 35 kb, respectively. Besides alkB, several alcohol/aldehyde
      dehydrogenase genes were also determined. A homolog of rubredoxin 2 of
      Pseudomonas putida was identified on 9E7 immediately downstream the alkB gene,
      but was lacking on 21G8. Unlike previous reports, the alkB genes on 9E7 and 21G8
      have opposite transcription directions to those of linked alcohol/aldehyde
      dehydrogenase genes. Phylogenetic analysis put these two deep-sea AlkBs into a
      unique branch of integral membrane hydroxylases. The two alkB genes (9E7-alkB and
      21G8-alkB) were cloned into pCom8 and introduced into two alkB expression host
      systems P. fluorescens KOB2 Delta 1 and P. putida GPo12 (pGEc47 Delta B). The
      transformed strains can grow on the n-alkanes from C5 to C16, indicating that
      both 9E7-AlkB and 21G8-AlkB have a wide substrate range. The data further
      indicate that the deep sea would be a rich resource for exploring novel alkane
      degrading strains and genes.

PMID- 18087671
TI  - Lysis efficiency of standard DNA extraction methods for Halococcus spp. in an
      organic rich environment.
AB  - The extraction of nucleic acids from a given environment marks a crucial and
      essential starting point in any molecular investigation. Members of Halococcus
      spp. are known for their rigid cell walls, and are thus difficult to lyse and
      could potentially be overlooked in an environment. Furthermore, the lack of a
      suitable lysis method hinders subsequent molecular analysis. The effects of six
      different DNA extraction methods were tested on Halococcus hamelinensis,
      Halococcus saccharolyticus and Halobacterium salinarum NRC-1 as well as on an
      organic rich, highly carbonated sediment from stromatolites spiked with
      Halococcus hamelinensis. The methods tested were based on physical disruption
      (boiling and freeze/thawing), chemical lysis (Triton X-100, potassium ethyl
      xanthogenate (XS) buffer and CTAB) and on enzymatic lysis (lysozyme). Results
      showed that boiling and freeze/thawing had little effect on the lysis of both
      Halococcus strains. Methods based on chemical lysis (Triton X-100, XS-buffer, and
      CTAB) showed the best results, however, Triton X-100 treatment failed to produce
      visible DNA fragments. Using a combination of bead beating, chemical lysis with
      lysozyme, and thermal shock, lysis of cells was achieved however DNA was badly
      sheared. Lysis of cells and DNA extraction of samples from spiked sediment proved
      to be difficult, with the XS-buffer method indicating the best results. This
      study provides an evaluation of six commonly used methods of cell lysis and DNA
      extraction of Halococcus spp., and the suitability of the resulting DNA for
      molecular analysis.

PMID- 18087673
TI  - Replication of reported genetic associations of PADI4, FCRL3, SLC22A4 and RUNX1
      genes with rheumatoid arthritis: results of an independent Japanese population
      and evidence from meta-analysis of East Asian studies.
AB  - We conducted population-based association tests for the four selected SNPs
      (rs2240340/padi4_94, rs7528684/fcrl3_3, rs3792876/slc2F2 and rs2268277/runx1)
      previously reported to be associated with rheumatoid arthritis (RA). The study
      population consisted of 950 unrelated Japanese subjects with RA and 507 controls,
      none of whom had previously been tested for these variants. Only the SNP
      rs2240340/padi4_94 was modestly associated with RA [allele odds ratio (OR) 1.22,
      95% confidence interval (CI) 1.04-1.43, P=0.012]. The most significant
      association effect was found for genotype contrast between minor and major allele
      homozygotes (OR 1.53, 95% CI 1.10-2.12, P=0.010). No other SNPs showed a
      statistically significant association with RA in our population. Meta-analysis of
      published studies and our new data confirmed a highly significant association
      between PADI4 gene SNPs and increased risk of RA in East Asian populations
      (allele fixed-effects summary OR 1.31, 95% CI 1.22-1.41, P<0.0001). We found some
      evidence for an association of either rs7528684/fcrl3_3 or rs3792876/slc2F2 with
      RA; however, because the magnitudes of effects were apparently much weaker than
      those reported in the initial positive reports, and there were substantial levels
      of inter-study OR heterogeneity, we concluded that additional studies are needed
      to fully understand the present results.

PMID- 18087674
TI  - The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell
      lines takes place through its aggregation on the cell membrane.
AB  - Human eosinophil cationic protein (ECP)/ ribonuclease 3 (RNase 3) is a protein
      secreted from the secondary granules of activated eosinophils. Specific
      properties of ECP contribute to its cytotoxic activities associated with defense
      mechanisms. In this work the ECP cytotoxic activity on eukaryotic cell lines is
      analyzed. The ECP effects begin with its binding and aggregation to the cell
      surface, altering the cell membrane permeability and modifying the cell ionic
      equilibrium. No internalization of the protein is observed. These signals induce
      cell-specific morphological and biochemical changes such as chromatin
      condensation, reversion of membrane asymmetry, reactive oxygen species production
      and activation of caspase-3-like activity and, eventually, cell death. However,
      the ribonuclease activity component of ECP is not involved in this process as no
      RNA degradation is observed. In summary, the cytotoxic effect of ECP is attained
      through a mechanism different from that of other cytotoxic RNases and may be
      related with the ECP accumulation associated with the inflammatory processes, in
      which eosinophils are present.

PMID- 18087675
TI  - Fine-tuning of cell signaling by glypicans.
AB  - Signaling peptides of the extracellular environment regulate cell biological
      processes underlying embryonic development, tissue homeostasis, and
      pathophysiology. The heparan sulphate proteoglycans, glypicans, have evolved as
      essential modulators of key regulatory proteins such as Wnt, Bmp, Fgf, and Shh.
      By acting on signal spreading and receptor activation, glypicans can control
      signal read-out and fate in targeted cells. Genetic and embryological studies
      have highlighted that glypicans act in a temporal and spatially regulated manner
      to modulate distinct cellular events. However, alterations of glypican function
      underlie human congenital malformations and cancer. Recent reports are starting
      to reveal their mechanism of action and how they can ensure tight modulation of
      cell signaling.

PMID- 18087677
TI  - Monitoring cataract surgical outcome in a Nigerian mission hospital.
AB  - AIM: To evaluate the visual outcome of cataract operations in a Nigerian mission
      hospital. METHODS: The computer system cataract surgery record forms were used to
      collect data on the first 100 consecutive cataract surgeries performed in January
      and part of February 2003 at a Nigerian mission hospital, Mercy Eye Centre, Abak.
      RESULTS: There were 54 males and 30 females (100 eyes). Sixteen patients had
      bilateral cataract. The mean age was 58.45 years (SD 13.58). Four patients were
      hypertensive, 3 diabetic, 2 both hypertensive and diabetic; and also 2 both
      hypertensive and asthmatic. Four patients had post-uveitic cataract, 3 traumatic
      cataract, 1 subluxated cataract not related to trauma and the rest had age
      related cataract. One patient each had age-related macular degeneration and
      glaucoma. Only 42 patients (49 eyes) kept with their follow-up visits until 12
      weeks post-operatively. Among these, pin hole or corrected visual acuity of 6/6
      6/18 was achieved in 35.4%, <6/18-6/60 in 50%, and <6/60 in 14.6%. Almost half of
      those with poor outcome were attributed to inappropriate selection. CONCLUSION:
      The main cause of poor visual outcome in our centre is unsuspected co-morbidity.
      In spite of this, there is potential for good quality cataract surgery in Africa.
      As we pay more attention to appropriate patient selection we expect our outcome
      to improve. Provision of facilities for biometry would also be a great help in
      this direction.

PMID- 18087676
TI  - CCDC134, a novel secretory protein, inhibits activation of ERK and JNK, but not
      p38 MAPK.
AB  - In this study, we report a novel gene, CCDC134 (coiled-coil domain containing
      134), that encodes a secretory protein that can inhibit the MAPK pathway as a
      novel human MAPK-regulating protein. The CCDC134 mRNA contains 1280 nucleotides,
      encoding a protein of 229 amino acids. CCDC134 is a classical secretory protein.
      Expression profile analysis by Northern blot, RT-PCR, immunohistochemistry and
      Western blot reveals that CCDC134 is widely expressed in normal adult tissues,
      tumor tissues and cell lines. Functional investigation reveals that
      overexpression of CCDC134 and its purified protein significantly inhibit
      transcriptional activity of Elk1 and phosphorylation of Erk and JNK/SAPK but not
      p38 MAPK. Conversely, specific siRNA against CCDC134 activates Elk1
      transcriptional activity and promotes Erk and JNK/SAPK phosphorylation. These
      results clearly indicate that CCDC134 is a novel member of the secretory family
      and down-regulates the Raf-1/MEK/ERK and JNK/ SAPK pathways.

PMID- 18087678
TI  - Inflammation, inflammatory cells and angiogenesis: decisions and indecisions.
AB  - Endothelial-immune cell cross-talk goes well beyond leukocyte and lymphocyte
      trafficking, since immune cells are able to intimately regulate vessel formation
      and function. Here we review the evidence that most immune cells are capable of
      polarization towards a dichotomous activity either inducing or inhibiting
      angiogenesis. In addition to the well-known roles of tumor associated
      macrophages, we find that neutrophils, myeloid-derived suppressor and dendritic
      cells clearly have the potential for influencing tumor angiogenesis. Further, the
      physiological functions of NK cells suggest that these cells may also show a
      potentially important role in pro- or anti-angiogenesis regulation within the
      tumor microenvironment. At the same time many angiogenic factors influence the
      activity and function of immune cells that generally favor tumor survival and
      tolerance. Thus the immune system itself represents a major pharmaceutical target
      and links angiogenesis inhibition to immunotherapy.

PMID- 18087680
TI  - Cardiac troponin-I: a predictor of prognosis in subarachnoid hemorrhage.
AB  - BACKGROUND: Release of cardiac biomarkers is reported in patients with
      subarachnoid hemorrhage (SAH). Data addressing the impact of cardiac injury on
      outcome in these patients is sparse. This study was conducted to ascertain the
      association of elevation of serum cardiac Troponin-I (cTnI) with mortality and
      neurological outcome in patients with SAH. METHODS: Medical records of all
      patients admitted with a diagnosis of SAH and at least one measured cTnI were
      reviewed. Demographic and clinical variables including admission neurological
      status were collected. Conservative and non-parametric statistics were used to
      assess association between cTnI and death or neurological outcome at discharge.
      RESULTS: The study group comprised of 83 patients with a mean age of 59 years.
      There was a female (60%) and African-American (60%) preponderance. At admission,
      the median Glasgow Coma Scale (GCS) was 9, and 47% had a severe Hunt-Hess grade
      (HHG) of > or =4. Elevation of cTnI was found in 31 (37%) patients and was
      associated with worse baseline Fisher grade (p=0.01) and neurological status: GCS
      score (p=0.006) and HHG (p=0.007). Patients with abnormal cTnI were more likely
      to die (55% vs.27%; odds ratio 1.3-8.4, p = 0.01) and had a worse GCS score (p =
      0.008) and HHG (p = 0.004) on discharge. On multivariate analysis, peak cTnI (p =
      0.04) and admission GCS score of <12 (p = 0.02) were independent predictors of
      death at discharge. CONCLUSION: Patients with subarachnoid hemorrhage and
      elevated cTnI are found to have worse neurological status at admission. These
      patients have a worse neurological outcome and in-hospital mortality.

PMID- 18087679
TI  - Synergistic effect of amlodipine and atorvastatin in reversing LDL-induced
      endothelial dysfunction.
AB  - PURPOSE: Statins and certain calcium channel blockers may improve nitric oxide
      (NO) release and endothelial function through various mechanisms, but their
      combined effects are not well understood. METHODS: The separate versus combined
      effects of amlodipine (AML) and atorvastatin (AT) on NO and peroxynitrite (ONOO-)
      were measured in human umbilical vein endothelial cells (HUVEC) in the presence
      and absence of low-density lipoprotein (LDL) using electrochemical nanosensors.
      RESULTS: The combination of AML (5 micromol/l) and AT (3-6 micromol/l) directly
      stimulated NO release that was about twofold greater than the sum of their
      separate effects (p < 0.05). This synergistic activity is attributed to enhanced
      endothelial NO synthase (eNOS) function and decreased cytotoxic ONOO-. LDL (100
      mg/dl) caused a dysfunction of HUVEC manifested by a 60% reduction in NO and an
      almost twofold increase in ONOO-. Treatment with AML/AT partially reversed the
      effects of LDL on endothelial function, including a 90% increase in NO and 50%
      reduction in ONOO-. Small-angle X-ray diffraction analysis indicates that AML and
      AT are lipophilic and share an overlapping molecular location in the cell
      membrane that could facilitate electron transfer for antioxidant mechanisms.
      CONCLUSION: These findings indicate a synergistic effect of AML and AT on an
      increase in NO concentration, reduction of nitroxidative stress. Also, AML/AT
      partially restored the NO level of LDL-induced dysfunctional endothelium. Their
      combined effects may be enhanced by antioxidant properties related to their
      intermolecular actions in the cell membrane and an increase in the expression and
      coupling of endothelial nitric oxide synthase.

PMID- 18087681
TI  - The journal and the field.

PMID- 18087683
TI  - Similar cardiac vagal withdrawal at the onset of arm and leg dynamic exercise.
AB  - Electrocardiogram RR intervals duration reduce rapidly in the first seconds of
      dynamic exercise mainly due to a cardiac vagal withdrawal. However, it remains
      unclear if this response varies between exercises performed with different body
      segments (i.e. arm vs. leg). Our aim was to compare the vagal withdrawal at the
      onset of arm and leg dynamic exercise. Cardiac vagal withdrawal was assessed by
      the 4-s exercise test (4sET), a pharmacologically validated and highly reliable
      procedure. Initially, 60 healthy subjects performed the 4sET using arms (ARM
      4sET) and legs (LEG 4sET), in a random order. Later, 20 of them repeated the
      testing, controlling for cycling rate and time of exercise onset within a RR
      interval, potential intervenient variables. Similar results were found for ARM
      and LEG 4sET considering the RR interval duration obtained immediately before the
      onset of exercise (RRB) (mean +/- SEM; 852 +/- 23 vs. 857 +/- 23 ms; P = 0.55),
      the shortest RR interval duration during exercise (RRC) (570 +/- 10 vs. 563 +/-
      10 ms; P = 0.22) and the cardiac vagal index (CVI), which is the ratio between
      RRB and RRC (1.49 +/- 0.03 vs. 1.52 +/- 0.03; P = 0.10). Furthermore, high
      intraclass correlation coefficients were found (RRB r (i) = 0.94, P < 0.001; RRC
      r (i) = 0.85, P < 0.001; CVI r (i) = 0.81, P < 0.001). We conclude that similar
      cardiac vagal withdrawal was induced by 4-s fast unloaded cycling exercise
      performed with arms or legs.

PMID- 18087684
TI  - Gravity orientation in social wasp comb cells (Vespinae) and the possible role of
      embedded minerals.
AB  - Social wasps and hornets maintain their nest in the dark. The building of the
      combs by all Vespinae is always in the direction of the gravitational force of
      Earth, and in each cell's ceiling, at least one 'keystone' is embedded and
      fastened by saliva. The sensory mechanisms that enable both building of sizeable
      symmetrical combs and nursing of the brood in the darkness merit investigation,
      and the aim of the present study was to identify and characterize the 'keystones'
      that exist in the ceiling and in the walls of the social wasp comb cells. Bio
      ferrography was used to isolate magnetic particles on slides. These slides, as
      well as original cells, were analyzed in an environmental scanning electron
      microscope by a variety of analytical tools. It was found that both the roof and
      the walls of each comb cell bear minerals, like ferrites, as well as Ti and Zr.
      The latter two elements are less abundant in the soil around the nest. Ti and Zr
      are known to reflect infrared (IR) light. IR imaging showed a thermoregulatory
      center in the dorsal thorax of the adult Oriental hornet. It is not known yet
      whether these insects can sense IR light.

PMID- 18087682
TI  - Inflammation in acute ischemic stroke and its relevance to stroke critical care.
AB  - Thrombolysis heralded a new era of acute intervention for ischemic stroke,
      accompanied by an increasing need for comprehensive acute critical care support.
      There remains the prospect of novel cerebral protection strategies. Cerebral
      ischemia initiates a complex cascade of events at genomic, molecular, and
      cellular levels, and inflammation is important in this cascade, both in the CNS
      and in the periphery. Closely linked events are induction of a classic acute
      phase protein response, activation of the hypothalamic-pituitary-adrenal axis
      (HPAA) and sympathetic nervous system (SNS), and rise in body temperature, all of
      which appear to importantly influence the outcome. Thrombolysis aside, various
      therapeutic strategies have been trialed without success recently, primarily
      directed at influencing neuronal activity and survival directly. Inflammation
      itself offers an attractive target, mainly because of its potential to exacerbate
      the spread of damage to the ischemic penumbra. A promising novel therapeutic
      approach is the interleukin-1 receptor antagonist (IL-1ra), which limits the
      action of the cytokine IL-1, a pivotal mediator in the pathophysiology of acute
      neurodegeneration. Critical care has much to offer some patients after acute
      ischemic stroke, including the delivery of acute interventions, often with very
      short therapeutic time windows, physiological support, and the management of
      complications. We discuss inflammation and its mediators in acute ischemic
      stroke, the systemic stress, and acute phase protein responses to acute ischemic
      stroke, how inflammation is relevant in deteriorating ischemic stroke, the impact
      of physiological variables, and both current and emerging interventions for acute
      ischemic stroke.

PMID- 18087685
TI  - Gold and gold working in Late Bronze Age Northern Greece.
AB  - Numerous objects of gold displaying an impressive variety of types and
      manufacturing techniques are known from the Late Bronze Age (LBA) contexts of
      Mycenaean Greece, but very little is known about the origin and processing of
      gold during the second millennium B.C: . Ancient literature and recent research
      indicate that northern Greece is probably the richest gold-bearing region in
      Greece, and yet, very little evidence exists regarding the exploitation of its
      deposits and the production as well as use of gold in the area during prehistory.
      The unusual find of a group of small stone crucibles at the prehistoric
      settlement of Thessaloniki Toumba, one with visible traces of gold melting,
      proves local production and offers a rare opportunity to examine the process of
      on-site gold working. Furthermore, the comparison of the chemical composition of
      prehistoric artefacts from two settlements with those of gold deposits in their
      immediate areas supports the local extraction of gold and opens up the prospect
      for some of the Mycenaean gold to have originated in northern Greece. The
      scarcity of gold items in northern Greek LBA contexts may not represent the
      actual amount of gold produced and consumed, but could be a result of the local
      social attitudes towards the circulation and deposition of artefacts from
      precious metals.

PMID- 18087686
TI  - Individual and collective choice: parallel prospecting and mining in ants.
AB  - Decision making is of crucial importance in the lives of both animals and humans.
      How decisions of group members scale up to group decisions is of great interest.
      Accordingly, we gave homeless ant colonies (n = 67) in three experiments a choice
      between two nest sites (with small, big or mixed sand grains), each of which had
      to be excavated to be habitable. Among the colonies that chose only one of the
      new nest sites, all preferred the ones that could be excavated most easily and
      quickly. There are interesting parallels between the collective choice of mining
      sites and the ability of certain ants to select short cuts; both involve positive
      feedback. However, in this paper, we discuss a mechanism whereby collective co
      ordination in the production of social infrastructure can occur in the absence of
      signalling.

PMID- 18087687
TI  - Non-breeding habitat preference affects ecological speciation in migratory
      waders.
AB  - Models of ecological speciation predict that certain types of habitat should be
      more conducive to species diversification than others. In this study, I test this
      hypothesis in waders of the sub-order Charadrii using the number of morphological
      sub-species per species as an index of diversity. I classified all members of
      this clade as spending the non-breeding season either coastally or inland and
      argue that these represent fundamentally different environments. Coastal mudflats
      are characterised by high predictability and patchy worldwide distribution,
      whilst inland wetlands are widespread but unpredictable. The results show that
      migratory species that winter coastally are sub-divided into more sub-species
      than those that winter inland. This was not the case for non-migratory species. I
      argue that coastal environments select for more rigid migratory pathways, whilst
      inland wetlands favour more flexible movement patterns. Population sub-division
      could then result from the passive segregation of breeding sites or from the
      active selection for assortative mating of ecomorphs.

PMID- 18087689
TI  - Hitting new barriers in ventilator-induced lung injury.

PMID- 18087688
TI  - The mechanisms of alloxan- and streptozotocin-induced diabetes.
AB  - Alloxan and streptozotocin are toxic glucose analogues that preferentially
      accumulate in pancreatic beta cells via the GLUT2 glucose transporter. In the
      presence of intracellular thiols, especially glutathione, alloxan generates
      reactive oxygen species (ROS) in a cyclic redox reaction with its reduction
      product, dialuric acid. Autoxidation of dialuric acid generates superoxide
      radicals, hydrogen peroxide and, in a final iron-catalysed reaction step,
      hydroxyl radicals. These hydroxyl radicals are ultimately responsible for the
      death of the beta cells, which have a particularly low antioxidative defence
      capacity, and the ensuing state of insulin-dependent 'alloxan diabetes'. As a
      thiol reagent, alloxan also selectively inhibits glucose-induced insulin
      secretion through its ability to inhibit the beta cell glucose sensor
      glucokinase. Following its uptake into the beta cells, streptozotocin is split
      into its glucose and methylnitrosourea moiety. Owing to its alkylating
      properties, the latter modifies biological macromolecules, fragments DNA and
      destroys the beta cells, causing a state of insulin-dependent diabetes. The
      targeting of mitochondrial DNA, thereby impairing the signalling function of beta
      cell mitochondrial metabolism, also explains how streptozotocin is able to
      inhibit glucose-induced insulin secretion.

PMID- 18087690
TI  - Preserved spontaneous breathing in acute lung injury: show me the money?

PMID- 18087691
TI  - Spontaneous breathing during airway pressure release ventilation in experimental
      lung injury: effects on hepatic blood flow.
AB  - OBJECTIVE: Positive pressure ventilation can affect systemic haemodynamics and
      regional blood flow distribution with negative effects on hepatic blood flow. We
      hypothesized that spontaneous breathing (SB) with airway pressure release
      ventilation (APRV) provides better systemic and hepatic blood flow than APRV
      without SB. DESIGN: Animal study with a randomized cross-over design. SETTING:
      Animal laboratory of Bonn University Hospital. SUBJECTS: Twelve pigs with oleic
      acid-induced lung injury. INTERVENTIONS: APRV with or without SB in random order.
      Without SB, either the upper airway pressure limit or the ventilator rate was
      increased to maintain constant pH and PaCO2. MEASUREMENTS AND RESULTS: Systemic
      haemodynamics were determined by double-indicator dilution, organ blood flow by
      coloured microspheres. Systemic blood flow was best during APRV with SB. During
      APRV with SB blood flow (ml g(-1) min(-1)) was 0.91+/-0.26 (hepatic arterial),
      0.29+/-0.05 (stomach), 0.64+/-0.08 (duodenum), 0.62+/-0.10 (jejunum), 0.53+/-0.07
      (ileum), 0.53+/-0.07 (colon), 0.46+/-0.09 (pancreas) and 3.59+/-0.55 (spleen).
      During APRV without SB applying high P(aw) it decreased to 0.13+/-0.01 (stomach),
      0.37+/-0.03 (duodenum), 0.29+/-0.03 (jejunum), 0.31+/-0.05 (ileum), 0.32+/-0.03
      (colon) and 0.23+/-0.04 (pancreas) p<0.01, respectively. During APRV without SB
      applying same Paw limits it decreased to 0.18+/-0.03 (stomach, p<0.01), 0.47+/
      0.06 (duodenum, p<0.05), 0.38+/-0.05 (jejunum, p<0.01), 0.36+/-0.03 (ileum,
      p<0.05), 0.39+/-0.05 (colon, p<0.05), and 0.27+/-0.04 (pancreas, p<0.01).
      Arterial liver blood flow did not change significantly when SB was abolished
      (0.55+/-0.11 and 0.63+/-0.11, respectively). CONCLUSIONS: Maintaining SB during
      APRV was associated with better systemic and pre-portal organ blood flow.
      Improvement in hepatic arterial blood flow was not significant.

PMID- 18087692
TI  - Recognition and labeling of delirium symptoms by intensivists: does it matter?
AB  - OBJECTIVE: The approach to acute cognitive dysfunction varies among physicians,
      including intensivists. Physicians may differ in their labeling of cognitive
      abnormalities in critically ill patients. We aimed to survey: (a) what Canadian
      intensive care unit (ICU) physicians identify as "delirium"; (b) choices of non
      pharmacological and pharmacological management; and (c) consultation patterns
      among ICU patients with cognitive abnormalities. DESIGN: A mail-in self
      administered survey was sent to Canadian intensivists registered with the
      Canadian Critical Care Society. The survey contained three clinical scenarios
      which described cognitively abnormal patients with: (a) hepatic encephalopathy;
      (b) multiple drug overdose; and (c) post-operative aortic aneurysm repair.
      Symptoms, which included fluctuating level of consciousness, inattention,
      disorientation, hallucinations, sleep/wake cycle disturbance, and paranoia, all
      fulfilled DSM-IV criteria for delirium. We asked for diagnoses in short-answer
      format for each scenario, and offered multiple selections of non-pharmacological
      and pharmacological therapies and consultation options. PARTICIPANTS: All
      intensivists registered with the Canadian Critical Care Society. MEASUREMENTS AND
      RESULTS: One-hundred thirty surveys were returned, for a response rate of 58.3%.
      When an etiological cognitive dysfunction diagnosis was obvious, 83-85% responded
      with the medical diagnosis to explain the cognitive abnormalities; only 43-55%
      used the term "delirium". In contrast, where an underlying medical problem was
      lacking, 74% of respondents diagnosed "delirium" (p=0.002). Non-pharmacological
      and pharmacological management varied considerably by physician and scenario but
      independently from whether the term "delirium" was selected. Commonly selected
      pharmacological agents were antipsychotics and benzodiazepines, followed by
      narcotics, non-narcotic analgesics, and other sedatives. Whether and when
      intensivists chose to consult other services varied. CONCLUSIONS: Canadian
      intensivists diagnose delirium based upon the presence or absence of an obvious
      medical etiology. Wide variation exists in approach to management, as well as
      patterns of consultation.

PMID- 18087693
TI  - Liquid chromatography-tandem mass spectrometric method for the determination of
      salivary 25-hydroxyvitamin D3: a noninvasive tool for the assessment of vitamin D
      status.
AB  - A sensitive liquid chromatography-electrospray ionization-tandem mass
      spectrometric (LC-ESI-MS/MS) method for the determination of 25-hydroxyvitamin
      D(3) [25(OH)D(3)] in human saliva has been developed and validated. The saliva
      was deproteinized with acetonitrile, purified using a Strata-X cartridge,
      derivatized with a Cookson-type reagent, 4-phenyl-1,2,4-triazoline-3,5-dione
      (PTAD), and subjected to LC-MS/MS. The PTAD derivative was much more easily
      ionized in positive-ESI-MS and efficiently produced a characteristic product ion
      during MS/MS, compared to the intact 25(OH)D(3). Methylamine was used as the
      mobile phase additive, and also effectively enhanced the assay sensitivity.
      Quantification was based on selected reaction monitoring, and 25-hydroxyvitamin
      D(4) was used as the internal standard. This method allowed the reproducible and
      accurate quantification of salivary 25(OH)D(3) using a 1.0-ml sample, and the
      limit of quantitation for 25(OH)D(3) was 2.0 pg/ml. The applicability of the
      developed method for clinical studies was then examined. There was a positive
      linear relationship (r (2) = 0.830) between the serum 25(OH)D(3) level, which is
      conventionally used as a means of assessing the vitamin D status, and the
      salivary 25(OH)D(3) level measured using the proposed method. The method also
      enabled the detection of the increase in the salivary 25(OH)D(3) level after the
      supplementation of vitamin D(3).

PMID- 18087694
TI  - Microfluidics in cell analysis.

PMID- 18087695
TI  - Perception of structured optic flow and random visual motion in infants and
      adults: a high-density EEG study.
AB  - Electroencephalogram (EEG) was used in 8-month-old infants and adults to study
      brain electrical activity as a function of perception of structured optic flow
      and random visual motion. A combination of visual evoked potential (VEP) analyses
      and analyses of temporal spectral evolution (TSE, time-dependent spectral power)
      was carried out. Significant differences were found for the N2 component of VEP
      for optic flow versus random visual motion within and between groups. Both adults
      and infants showed shorter latencies for structured optic flow than random visual
      motion, and infants showed longer latencies, particularly for random visual
      motion, and larger amplitudes than adults. Both groups also showed significant
      differences in induced activity when TSE of the two motion stimuli (optic flow
      and random visual motion) was compared with TSE of a static dot pattern. Infants
      showed an induced decrease in the amplitudes in theta-band frequency, while
      adults showed an induced increase in beta-band frequency. Differences in induced
      activity for the two motion stimuli could, however, not be observed. Brain
      activity related to motion stimuli is different for infants and adults and the
      differences are observed both in VEPs and in induced activity of the EEG. To
      investigate how changes in locomotor development are related to accompanying
      changes in brain activity associated with visual motion perception, more data of
      infants with different experiences in self-produced locomotion are required.

PMID- 18087696
TI  - Distractor effects on saccade trajectories: a comparison of prosaccades,
      antisaccades, and memory-guided saccades.
AB  - The present study investigated the contribution of the presence of a visual
      signal at the saccade goal on saccade trajectory deviations and measured
      distractor-related inhibition as indicated by deviation away from an irrelevant
      distractor. Performance in a prosaccade task where a visual target was present at
      the saccade goal was compared to performance in an anti- and memory-guided
      saccade task. In the latter two tasks no visual signal is present at the location
      of the saccade goal. It was hypothesized that if saccade deviation can be
      ultimately explained in terms of relative activation levels between the saccade
      goal location and distractor locations, the absence of a visual stimulus at the
      goal location will increase the competition evoked by the distractor and affect
      saccade deviations. The results of Experiment 1 showed that saccade deviation
      away from a distractor varied significantly depending on whether a visual target
      was presented at the saccade goal or not: when no visual target was presented,
      saccade deviation away from a distractor was increased compared to when the
      visual target was present. The results of Experiments 2-4 showed that saccade
      deviation did not systematically change as a function of time since the offset of
      the target. Moreover, Experiments 3 and 4 revealed that the disappearance of the
      target immediately increased the effect of a distractor on saccade deviations,
      suggesting that activation at the target location decays very rapidly once the
      visual signal has disappeared from the display.

PMID- 18087697
TI  - Goal-directed reaching: movement strategies influence the weighting of
      allocentric and egocentric visual cues.
AB  - The location of an object in peripersonal space can be represented with respect
      to our body (i.e., egocentric frame of reference) or relative to contextual
      features and other objects (i.e., allocentric frame of reference). In the current
      study, we sought to determine whether the frame, or frames, of visual reference
      supporting motor output is influenced by reach trajectories structured to
      maximize visual feedback utilization (i.e., controlled online) or structured
      largely in advance of movement onset via central planning mechanisms (i.e.,
      controlled offline). Reaches were directed to a target embedded in a pictorial
      illusion (the induced Roelofs effect: IRE) and advanced knowledge of visual
      feedback was manipulated to influence the nature of reaching control as reported
      by Zelaznik et al. (J Mot Behav 15:217-236, 1983). When vision could not be
      predicted in advance of movement onset, trajectories showed primary evidence of
      an offline mode of control (even when vision was provided) and endpoints
      demonstrated amplified sensitivity to the illusory (i.e., allocentric) features
      of the IRE. In contrast, reaches performed with reliable visual feedback
      evidenced a primarily online mode of control and showed increased visuomotor
      resistance to the IRE. These findings suggest that the manner a reaching response
      is structured differentially influences the weighting of allocentric and
      egocentric visual information. More specifically, when visual feedback is
      unavailable or unpredictable, the weighting of allocentric visual information for
      the advanced planning of a reach trajectory is increased.

PMID- 18087698
TI  - Ritodrine pharmacokinetics in twin pregnancy patients.
AB  - OBJECTIVES: To establish a rational ritodrine therapy in relation to serum
      ritodrine concentration, we examined 14 twin pregnancy patients and determined
      their pharmacokinetic data. METHODS: We measured serum concentrations of
      ritodrine in twin pregnancy patients using high-performance liquid chromatography
      (HPLC). RESULTS: The twin pregnancy patients all exhibited linear ritodrine
      pharmacokinetic profiles. There was a statistically significant but slight
      negative correlation between gestation period and ritodrine clearance (y=
      0.038x+2.75, r=0.349, p<0.001) among all patients. However, when analyzed on an
      individual basis, there was a high correlation found in three of the 14 patients.
      CONCLUSION: Due to a decrease in total body clearance in three of the 14
      patients, overall serum concentration of ritodrine increased at the end of the
      pregnancies. To further characterize ritodrine kinetics, additional studies are
      needed to determine an effective and safe therapy for ritodrine use in twin
      pregnancy patients.

PMID- 18087699
TI  - Discrepancy between glucose metabolism and sympathetic nerve terminals in a
      patient with metastatic paraganglioma.

PMID- 18087700
TI  - Osteochondritis dissecans.

PMID- 18087701
TI  - Stability of the T-DNA flanking regions in transgenic Arabidopsis thaliana plants
      under influence of abiotic stress and cultivation practices.
AB  - Genetic transformation is often associated with different rearrangements of the
      plant genome at the site of insertion. Therefore the question remains weather
      these T-DNA insertion sites are more prone to genotoxic stresses. Here, we
      studied the impact of propagation through generations, the influence of gene
      stacking and of photo oxidative stress caused by high light intensity on the
      stability of the transgene flanking regions in the model plant Arabidopsis
      thaliana. Conformational Sensitive Capillary Electrophoresis (CSCE), RFLP and
      sequencing were deployed in this analysis in order to study the proximal 100 bp
      and the long-range T-DNA flanking sequences. By screening seven transgenic lines
      no evidence for occurrence of mutation events were found, implying that the
      nucleotide sequence of the T-DNA flanking regions of the studied events is
      unlikely to be unstable.

PMID- 18087702
TI  - Characterization of a family of Arabidopsis receptor-like cytoplasmic kinases
      (RLCK class VI).
AB  - The receptor-like cytoplasmic protein kinases (RLCKs) are plant-specific proteins
      encoded by almost 200 genes in the Arabidopsis genome. Despite of their high
      number, the available information on the potential function of RLCKs is very
      limited. In this report, the sequence analysis and the gene expression pattern of
      14 members of one of the Arabidopsis RLCK families (RLCK class VI) are described.
      Sequence comparison indicated that gene duplication played a significant role in
      the formation of the kinase family and that several members carry an N-terminal
      "universal stress protein" (UspA) domain. In order to gain insight into the
      potential function of the RLCK VI kinases, real-time quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) was used to determine the
      relative transcript levels in the various organs of the Arabidopsis plant as well
      as under a series of abiotic stress/hormone treatments in seedlings. The obtained
      data revealed the differentially regulated expression of the genes in agreement
      with a high variability of sequence elements in their promoters. The divergent
      expression patterns indicate that the encoded kinase proteins may be involved in
      a wide variety of signal transduction pathways related to plant development and
      stress responses. The significance of gene duplication and expression divergence
      in the extension of the Arabidopsis RLCK VI family during evolution is discussed.

PMID- 18087703
TI  - Salinity-dependent changes in Na(+)/K (+)-ATPase content of mitochondria-rich
      cells contribute to differences in thermal tolerance of Mozambique tilapia.
AB  - The Mozambique tilapia (Oreochromis mossambicus) is prone to osmoregulatory
      disturbances when faced with fluctuating ambient temperatures. To investigate the
      underlying causes of this phenomenon, freshwater (FW)- and seawater (SW)
      acclimated tilapia were transferred to 15, 25, or 35 degrees C for 2 weeks, and
      along with typically used indicators of osmoregulatory status [plasma osmolality
      and branchial and intestinal specific Na(+), K(+)-ATPase (NKA) activity], we used
      tissue microarrays (TMA) and laser-scanning cytometry (LSC) to characterize the
      effects of temperature acclimation. Tissue microarrays were stained with
      fluorescently labeled anti-Na(+), K(+)-ATPase antibodies that allowed for the
      quantification of NKA abundance per unit area within individual branchial
      mitochondria-rich cells (MRCs) as well as sections of renal tissue. Mitochondria
      rich cell counts and estimates of size were carried out for each treatment by the
      detection of DASPMI fluorescence. The combined analyses showed that SW fish have
      larger but fewer MRCs that contain more NKA per unit area. After a 2-week
      acclimation to 15 degrees C tilapia experienced osmotic imbalances in both FW and
      SW that were likely due to low NKA activity. SW-acclimated fish compensated for
      the low activity by increasing MRC size and subsequently the concentration of NKA
      within MRCs. Although there were no signs of osmotic stress in FW-acclimated
      tilapia at 25 degrees C, there was an increased NKA capacity that was most likely
      mediated by a higher MRC count. We conclude on the basis of the different
      responses to temperature acclimation that salinity-induced changes in the NKA
      concentration of MRCs alter thermal tolerance limits of tilapia.

PMID- 18087704
TI  - Western diseases: current concepts and implications for pediatric surgery
      research and practice.
AB  - The term "Western diseases" refers to those conditions that are rare or absent in
      underdeveloped areas of the Third World and increase in frequency with adoptions
      of Western customs. In adults, they include such common conditions as coronary
      artery disease, essential hypertension, appendicitis, cholesterol gall stones,
      and colon cancer. The best examples of Western diseases in the pediatric
      population are asthma, allergies, appendicitis, and inflammatory bowel disease.
      Limited data from sub-Saharan Africa suggest other pediatric surgical conditions
      may fall into this category, including hypertrophic pyloric stenosis,
      gastroesophageal reflux, perirectal abscess, anal fissure, gastroschesis, and
      neuroblastoma. Existing theories for the origins of Western diseases have
      postulated a role for decreased dietary fiber, improved hygiene, fetal
      programming, and a protective effect of tropical enteropathy. How these factors
      might relate to the rise of appendicitis, inflammatory bowel disease, and
      possibly other common pediatric surgical diseases in industrialized societies
      remains poorly understood. Further research is needed to better define
      geographical differences in common pediatric surgical conditions and to
      investigate how genetic and environmental factors interact to modify risk of
      disease. Understanding the molecular mechanisms that give rise to Western
      diseases could lead to new therapeutic and prevention strategies for some of the
      most common pediatric surgical conditions in industrialized countries.

PMID- 18087705
TI  - TDP-43 immunoreactivity in anoxic, ischemic and neoplastic lesions of the central
      nervous system.
AB  - TDP-43 proteinopathies are a newly categorized group of neurodegenerative
      diseases characterized by progressive cognitive and motor impairments associated
      with the abnormal accumulation and mislocalization of the nuclear TAR-DNA-binding
      protein-43 (TDP-43) in neurons and glia. Little is known about the expression and
      distribution of TDP-43 in normal and pathologic states. To determine whether TDP
      43 inclusions arise in response to metabolic insults such as anoxia or ischemia,
      a panel of anoxic, ischemic and neoplastic lesions was examined for TDP-43
      expression by immunohistochemistry. These lesions did not exhibit TDP-43
      inclusions like those seen in neurodegenerative frontotemporal dementia and motor
      neuron disease. However, TDP-43 was found in Rosenthal fibers and eosinophilic
      granular bodies associated with low-grade tumors and reactive brain tissue.
      Furthermore, cytoplasmic TDP-43 was seen in M-phase tumor cells, but not in
      mitotic spindles. These findings expand our knowledge of the distribution and
      localization of TDP-43, and indicate that the TDP-43 inclusions seen in
      frontotemporal dementias and motor neuron diseases are specific to a
      neurodegenerative process.

PMID- 18087706
TI  - Arthroscopically assisted coracoclavicular ligament reconstruction for chronic
      acromioclavicular joint instability.
AB  - The treatment of symptomatic chronic acromioclavicular joint dislocations can be
      challenging. Different surgical procedures have been described in the literature.
      We present an arthroscopically assisted stabilization using a gracilis tendon
      transclavicular-transcoracoid loop technique augmented with a Tight-Rope
      (Arthrex, Naples, FL, USA). In contrast to the classic Weaver-Dunn procedures
      this technique is designed to stabilize the acromioclavicular joint by recreating
      the anatomy of the coracoclavicular ligaments via a minimal invasive approach.

PMID- 18087707
TI  - Practice of antenatal clinical breast examination as a method of early detection
      of breast cancer by health care providers in a low resource setting.
AB  - BACKGROUND: Clinical breast examination (CBE) provides an important screening
      tool for the earlier detection of breast cancer among women in populations such
      as ours where mammography is not widely available as a screening tool. There is a
      paucity of data on the level of practice of antenatal CBE by health-care
      providers at Aba, South Eastern Nigeria. OBJECTIVE: To determine the level of
      practice of antenatal CBE by health-care providers as a method of early detection
      of breast cancer. METHOD: A descriptive study involving 100 consecutive and
      consenting patients at the antenatal clinic of Abia State University Teaching
      Hospital, Aba, South Eastern Nigeria over the period 1 June-15 June 2007 was
      carried out. Using a structured questionnaire, the respondents' socio-demographic
      data were obtained, as well as their knowledge of breast cancer and of what
      breast cancer examination screens for, and self-reported data on their having
      ever received CBE during the current antenatal period. RESULTS: The knowledge of
      breast cancer was poor. Although 99% of the women had heard of breast cancer,
      only 34% of them knew what breast examination screened for, whilst only 1 and 2%
      had received CBE by doctors and nurses, respectively, during the current
      antenatal period. No breast abnormalities or suspicious nodes were detected
      during the antenatal CBEs. CONCLUSION: The level of practice of routine antenatal
      CBE by health-care providers is very low in our setting. Health-care providers
      should perform a thorough breast examination at the first prenatal visit and
      maintain a high index of suspicion for breast cancer throughout pregnancy.

PMID- 18087708
TI  - Visceral leishmaniasis and pregnancy: analysis of cases reported in a central
      western region of Brazil.
AB  - OBJECTIVES: Because of the large number of cases of visceral leishmaniasis (VL)
      recorded in Brazil over the last few years, this disease has been showing
      characteristics different from previously known ones. We report cases of pregnant
      women treated for VL, describing their course and outcome and the
      chemotherapeutic medication used according to the clinical signs and symptoms of
      each patient. STUDY DESIGN: We report five cases of pregnant women treated for VL
      in a central-western region of Brazil. RESULTS: No case of vertical transmission
      was observed, even in patients who were treated after delivery. One of the
      patients with a late diagnosis made after the onset of symptoms died. Thus, the
      treatment of VL during pregnancy reduces maternal mortality and the rate of
      vertical transmission of the disease, being safe and effective as long as the
      disease is diagnosed early. CONCLUSION: At present, amphotericin B and its
      derivatives appear to be the best therapeutic option for the mother-child
      binomial.

PMID- 18087709
TI  - Hematopoietic cell renewal systems: mechanisms of coping and failing after
      chronic exposure to ionizing radiation.
AB  - On the occasion of the first international workshop on systems radiation biology
      we review the role of cell renewal systems in maintaining the integrity of the
      mammalian organism after irradiation. First, 11 radiation emergencies
      characterized by chronic or protracted exposure of the human beings to ionizing
      irradiation were "revisited". The data provide evidence to suggest that at a
      daily exposure of about 10-100 mSv, humans are capable of coping with the excess
      cell loss for weeks or even many months without hematopoietic organ failure.
      Below 10 mSv/day, the organisms show some cellular or subcellular indicators of
      response. At dose rates above 100 mSv/day, a progressive shortening of the life
      span of the irradiated organism is observed. To elucidate the mechanisms relevant
      to tolerance or failure, the Megakaryocyte-thrombocyte cell renewal system was
      investigated. A biomathematical model of this system was developed to simulate
      the development of thrombocyte concentration as a function of time after onset of
      chronic radiation exposure. The hematological data were taken from experimental
      chronic irradiation studies with dogs at the Argonne National Laboratory, USA.
      The results of thrombocyte response patterns are compatible with the notion of an
      "excess cell loss" (compared to the steady-state) in all proliferative cell
      compartments, including the stem cell pool. The "excess cell loss" is a function
      of the daily irradiation dose rate. Once the stem cell pool is approaching an
      exhaustion level, a "turbulence region" is reached. Then it takes a very little
      additional stress for the system to fail. We conclude that in mammalian radiation
      biology (including radiation medicine), it is important to understand the
      physiology and pathophysiology of cell renewal systems in order to allow
      predicting the development of radiation induced lesions.

PMID- 18087710
TI  - Systems biology and its potential role in radiobiology.
AB  - About a century ago, Conrad Roentgen discovered X-rays, and Henri Becquerel
      discovered a new phenomenon, which Marie and Pierre Curie later coined as radio
      activity. Since their seminal work, we have learned much about the physical
      properties of radiation and its effects on living matter. Alas, the more we
      discover, the more we appreciate the complexity of the biological processes that
      are triggered by radiation exposure and eventually lead (or do not lead) to
      disease. Equipped with modern biological methods of high-throughput
      experimentation, imaging, and vastly increased computational prowess, we are now
      entering an era where we can piece some of the multifold aspects of radiation
      exposure and its sequelae together, and develop a more systemic understanding of
      radiogenic effects such as radio-carcinogenesis than has been possible in the
      past. It is evident from the complexity of even the known processes that such an
      understanding can only be gained if it is supported by mathematical models. At
      this point, the construction of comprehensive models is hampered both by
      technical inadequacies and a paucity of appropriate data. Nonetheless, some
      initial steps have been taken already and the generally increased interest in
      systems biology may be expected to speed up future progress. In this context, we
      discuss in this article examples of relatively small, yet very useful models that
      elucidate selected aspects of the effects of exposure to ionizing radiation and
      may shine a light on the path before us.

PMID- 18087711
TI  - Anti-inflammatory effect of angiotensin type 1 receptor antagonist on endotoxin
      induced uveitis in rats.
AB  - BACKGROUND: Angiotensin II type 1 (AT1) receptor-antagonists are widely used for
      treatment of hypertension. Recent studies have demonstrated a protective effect
      of renin angiotensin system (RAS) antagonism against immune-mediated inflammatory
      diseases such as myocarditis, chronic allograft rejection, antiglomerular
      basement membrane nephritis, colitis, and arthritis. However, only a few reports
      have demonstrated the effect of RAS in ocular inflammatory conditions. The
      purpose of this study was to investigate the anti-inflammatory effect of a
      selective AT1 receptor antagonist, losartan, on endotoxin-induced uveitis (EIU)
      and compare the effect on experimental autoimmune uveoretinitis (EAU). METHODS:
      To induce EIU, 7-week-old Lewis rats were injected subcutaneously with 200 microg
      lipopolysaccharide (LPS). Losartan was administered intravenously at the same
      time. The aqueous humor was collected from eyes 24 h after LPS injection. The
      number of infiltrating cells, protein concentration, and levels of tumor necrosis
      factor (TNF)-alpha and monocyte chemoattractant protein-1 (MCP-1) in the aqueous
      humor were determined. The collected eyes were immunohistochemically stained with
      monoclonal antibody for activated nuclear factor (NF)-kappaB. To induce EAU,
      C57BL/6 mice (6-8 weeks old) were immunized with human interphotoreceptor
      retinoid binding protein (hIRBP)-derived peptide emulsified in complete Freund's
      adjuvant (CFA) and concomitantly injected with purified Bordetella pertussis
      toxin (PTX). Clinical severity of EAU and T cell proliferative response were
      analyzed. RESULTS: Losartan significantly suppressed the development of EIU.
      Numbers of aqueous cells of control EIU rats, those from EIU rats treated with 1
      or 10 mg/kg of losartan were 75.3+/-45.6 x 10(5), 27.9+/-8.1 x 10(5), or 41.3+/
      30.9 x 10(5) cells/ml respectively (p<0.01 vs control). Aqueous protein, TNF
      alpha, and MCP-1 levels were also significantly decreased in a manner dependent
      on the amount of losartan administered (p<0.01). Treatment of EIU rats with
      losartan suppressed activation of NF-kappaB at the iris ciliary body. Thus, the
      suppressive effect of losartan on ocular inflammation in EIU appeared to result
      from down-regulation of NF-kappaB activation and reduction of inflammatory
      cytokine production. On the other hand, in the EAU model, neither the clinical
      score nor the antigen-specific T cell proliferative response was significantly
      influenced by the treatment with losartan. CONCLUSIONS: The present findings
      indicate that RAS may be involved in the acute inflammation of the eye, but not
      in T cell-dependent ocular autoimmunity. Antagonism of the RAS may be a potential
      prophylactic strategy for treatment of the human acute ocular inflammation.

PMID- 18087712
TI  - Quercetin inhibits choroidal and retinal angiogenesis in vitro.
AB  - BACKGROUND: Quercetin is a natural substance found abundantly in grapes, red wine
      and other food products. In this study, we examined the effect of quercetin on
      choroidal and retinal angiogenesis in vitro using rhesus choroids-retina
      endothelial cell line (RF/6A). METHODS: RF/6A cells were cultured in Dulbecco's
      Modified Eagle's Medium (DMEM) containing 10% fetal bovine serum. Then cells were
      treated with different concentrations (from 0 to 100 microM) of quercetin. The
      cell proliferation was assessed using choromogenic methylthiazol tetrazolium
      bromide (MTT) dye after 24, 48 and 72 hours. Cell migration after 24-hour
      incubation with quercetin was investigated by wound assay. Following exposure to
      the various concentrations of quercetin for 24 hours, tube formation on matrigel
      by endothelial cells was also analyzed. Apoptosis was measured by flow cytometry
      using annexin V-FITC and propidium iodide staining. RESULTS: Quercetin inhibits
      endothelial cell proliferation in a dose-dependent fashion; 10.1%, 42.6% and
      65.2% inhibition on treating with 10, 50 and 100 microM Quercetin respectively.
      The migration and tube formation of RA/6A cells were also significantly inhibited
      by quercetin in a dose-dependent manner. Flow cytometric analysis showed that the
      percentages of apoptotic cells were slightly increased only in 100 microM
      quercetin-treated cells. CONCLUSIONS: Our results show that quercetin inhibits
      choroidal and retinal angiogenesis in vitro. Further studies are ongoing to
      evaluate this drug as a potential candidate for the treatment of choroidal or
      retinal neovascularization.

PMID- 18087713
TI  - Retained intraocular foreign body masquerading as malignant melanoma of the iris.

PMID- 18087715
TI  - Molecular basis for genistein-induced inhibition of Kir2.3 currents.
AB  - Inwardly rectifying potassium channels play an important role in the maintenance
      of membrane potential in neurons and myocardium. Identification of functional
      regulation mechanisms concerning these channels may lead to the development of
      specific modulators for these channels. Genistein is an isoflavone with potent
      inhibitory activity on protein tyrosine kinase. In this study, we have found that
      among three members of the Kir family (Kir2.3, Kir2.1, and Kir3.4* [a highly
      active mutant of Kir3.4, Kir3.4-S143T]) we tested, genistein significantly
      inhibited Kir2.3 currents. Using the two-electrode voltage clamp technique, we
      have demonstrated that micromole concentrations of genistein concentration
      dependently and reversibly inhibited the currents of Kir2.3 channel expressed in
      Xenopus oocytes with an IC50 of 16.9+/-2.8 microM. Using the whole-cell patch
      clamp technique, genistein also inhibited the currents of Kir2.3 channel
      expressed in HEK293 cells with an IC50 of 19.3+/-3.2 microM. Genistein had little
      or no effect on Kir2.1 and Kir3.4* currents. The effect of genistein on Kir2.3
      currents was not affected by vanadate, a potent protein tyrosine phosphatase
      inhibitor. Furthermore, the effect of genistein was not mimicked by daidzein, an
      inactive analogue of genistein, or another potent tyrosine kinase inhibitor,
      tyrphostin 23. Chimeras between Kir2.3 and Kir2.1 channels were constructed to
      identify molecular basis that distinguished the effect of genistein on these
      channels. It was found that the transmembrane domains and the pore region of
      Kir2.3 channel were important determinant for high sensitivity for genistein
      inhibition.

PMID- 18087716
TI  - A tip-high, Ca(2+) -interdependent, reactive oxygen species gradient is
      associated with polarized growth in Fucus serratus zygotes.
AB  - We report the existence of a tip-high reactive oxygen species (ROS) gradient in
      growing Fucus serratus zygotes, using both 5-(and 6-) chloromethyl-2',7'
      dichlorodihydrofluorescein and nitroblue tetrazolium staining to report ROS
      generation. Suppression of the ROS gradient inhibits polarized zygotic growth;
      conversely, exogenous ROS generation can redirect zygotic polarization following
      inhibition of endogenous ROS. Confocal imaging of fluo-4 dextran distributions
      suggests that the ROS gradient is interdependent on the tip-high [Ca(2+)](cyt)
      gradient which is known to be associated with polarized growth. Our data support
      a model in which localized production of ROS at the rhizoid tip stimulates
      formation of a localized tip-high [Ca(2+)](cyt) gradient. Such modulation of
      intracellular [Ca(2+)](cyt) signals by ROS is a common motif in many plant and
      algal systems and this study extends this mechanism to embryogenesis.

PMID- 18087717
TI  - Development of the nervous system in the brittle star Amphipholis kochii.
AB  - There are several studies of neural development in various echinoderms, but few
      on ophiuroids, which develop indirectly via the production of pluteus larvae, as
      do echinoids. To determine the extent of similarity of neuroanatomy and neural
      development in the ophiuroids with other echinoderm larvae, we investigated the
      development of the nervous system in the brittle star Amphipholis kochii
      (Echinodermata: Ophiuroidea) by immunohistochemistry. Immunoreactive cells first
      appeared bilaterally in the animal pole at the late gastrula stage, and there was
      little migration of the neural precursors during A. kochii ontogeny, as is also
      the case in echinoids and holothuroids. On the other hand, neural specification
      in the presumptive ciliary band near the base of the arms does occur in ophiuroid
      larvae and is a feature they share with echinoids and ophiuroids. The
      ophiopluteus larval nervous system is similar to that of auricularia larvae on
      the whole, including the lack of a fine network of neurites in the epidermis and
      the presence of neural connections across the oral epidermis. Ophioplutei possess
      a pair of bilateral apical organs that differ from those of echinoid echinoplutei
      in terms of relative position. They also possess coiled cilia, which may possess
      a sensory function, but in the same location as the serotonergic apical ganglia.
      These coiled cilia are thought to be a derived structure in pluteus-like larvae.
      Our results suggest that the neural specification in the animal plate in
      ophiuroids, holothuroids, and echinoids is a plesiomorphic feature of the
      Ambulacraria, whereas neural specification at the base of the larval arms may be
      a more derived state restricted to pluteus-like larvae.

PMID- 18087718
TI  - Peritumoural, but not intratumoural, lymphatic vessel density and invasion
      correlate with colorectal carcinoma poor-outcome markers.
AB  - To evaluate whether lymphatic vessel density (LVD) and lymphatic vessel invasion
      (LVI) are useful markers of worse outcome in colorectal carcinoma and if LVD and
      LVI correlate to the classical clinical-pathological parameters, we analysed 120
      cases of colorectal carcinomas selected from the files of Division of Pathology,
      Hospital das Clinicas, Sao Paulo University, Brazil. Assessment of LVD and LVI
      was performed by immunohistochemical detection of lymphatic vessels, using the
      monoclonal antibody D2-40. Higher LVD was found in the intratumoural area, when
      comparing with normal and peritumoural areas (p < 0.001). However, peritumoural
      LVD, but not intratumoural, correlated with both colonic-wall-invasion depth (p =
      0.037) and liver metastasis (p = 0.012). Remarkably, LVI was found associated
      with local invasion (p = 0.016), nodal metastasis (p = 0.022) and hepatic
      metastasis (p < 0.001). Peritumoural LVD and LVI are directly related to
      histopathological variables indicative of poor outcome such as lymph-node status
      and liver metastasis.

PMID- 18087719
TI  - Feasibility of percutaneous organ biopsy as part of a minimally invasive
      perinatal autopsy.
AB  - To determine the feasibility of percutaneous fetal organ biopsies in the context
      of a 'minimally invasive' perinatal autopsy after stillbirth and termination for
      abnormality is the aim of this study. We assessed successful biopsy rate and the
      proportion adequate for histological examination in 30 fetuses undergoing organ
      sampling before autopsy. The relationship between gestational age, body weight,
      death-biopsy interval, operator experience and successful biopsy rate was
      investigated. Significant findings from conventional block histology were
      compared with corresponding percutaneous biopsies. Of 210 organ biopsies
      attempted from seven target organs, 107 were obtained, of which 94 were adequate
      for pathological comment. The median delivery-autopsy interval was 4 (range 2-11)
      days. Adequate samples were obtained from the lung in 86% cases (95% CI 68, 96%),
      liver 76% (95% CI 56, 90%) and less frequently for the myocardium, kidney,
      adrenal, thymus and spleen. There was no relationship between biopsy success and
      time to biopsy, gestational age, body weight and user experience. No histological
      abnormalities found at autopsy were diagnosed from needle biopsies. Although
      targeted percutaneous biopsies appear feasible for some organs, fewer than 50% of
      all biopsies are adequate for histological examination. This technique cannot be
      considered to provide useful clinical information as part of a 'minimally
      invasive' perinatal autopsy.

PMID- 18087720
TI  - Molecular interaction between prion protein and GFAP both in native and
      recombinant forms in vitro.
AB  - Gliosis of glial fibrillary acidic protein (GFAP) associated astrocytes is
      considered to be one of the hallmarks of transmissible spongiform
      encephalopathies (TSEs). In the present study, remarkable GFAP-PrP(Sc) or GFAP
      PrP(C) complexes were separately detected in the brain homogenates of 263 K
      (Scrapie)-infected or normal hamsters by co-immunoprecipitation assay. To get
      more exact molecular evidences for interaction between prion protein (PrP) and
      GFAP, various recombinant PrP or GFAP proteins were expressed using prokaryotic
      expressing and in vitro translation system. Using pull down and co
      immunoprecipitation assays, reliable molecular interaction between PrP and GFAP
      was observed, and proteinase K (PK)-digested PrP(Sc) molecules were confirmed to
      be able to bind the recombinant GFAP specifically as well. The region within PrP
      that was responsible for interaction with GFAP was narrowed to PK-resistant core
      of PrP (i.e. aa 91-230). The study of the association of PrP with GFAP supplies
      the molecular evidence for the observation of co-localization of PrP(Sc) and GFAP
      in the brains of TSEs and may further provide insight into a potential role of
      GFAP in the biological function of PrP and the pathogenesis of prion diseases.

PMID- 18087721
TI  - The functions of herpesvirus-encoded microRNAs.
AB  - Bioinformatic and direct cloning approaches have led to the identification of
      over 100 novel miRNAs expressed in DNA viruses, although the function of the
      majority of these small regulatory RNA molecules is unclear. Recently, a number
      of reports have now identified potential targets of viral miRNAs, including
      cellular and viral genes as well as an ortholog of an important immuno-regulatory
      cellular miRNA. In this review, we will cover the identification and
      characterization of miRNAs expressed in the herpesvirus family and discuss the
      potential significance of their role in viral infection.

PMID- 18087722
TI  - The history of cytomegalovirus and its diseases.
AB  - Intranuclear inclusions typical of cytomegalovirus infections were first noticed
      in 1881 by German scientists who thought they represented protozoa. After viruses
      were grown in cell cultures, Weller, Smith and Rowe independently isolated and
      grew CMV from man and mice in 1956-1957. Antibodies in 30-100% of normal adults
      indicate not only a past infection, but the presence of a present latent
      infection. The presence of CMV DNA in tissues and most organs surveyed indicates
      the ubiquity of latent infection. CMV disease requires the virus and some
      deficiency of immunity such as occurs in the immature fetus, in AIDS, and in
      transplant patients on immunosuppressive drugs. Antiviral agents can inhibit CMV
      replication but they cannot prevent or cure latent infections. A pharmacological
      approach using the many leads in understanding latency is needed.

PMID- 18087723
TI  - Cloning and characterization of a cDNA clone encoding calreticulin from
      Haemaphysalis qinghaiensis (Acari: Ixodidae).
AB  - The application of anti-tick vaccine has been shown to be the most promising
      alternative strategy compared to the current use of acaricides that suffer from a
      number of serious limitations. The success of this method is dependent upon
      identification and cloning of potential tick vaccine antigens. Previously, we
      have cloned 21 positive clones (named from Hq02 to Hq22) by immunoscreening
      complimentary DNA (cDNA) libraries of Haemaphysalis qinghaiensis; however, some
      of those clones did not contain open reading frames (ORF). In this study, we
      amplified the entire sequence of Hq07 by using rapid amplification of the cDNA
      ends. Hq07 contains an ORF of 1,233 bp that encodes for 410 amino acid residues
      with a coding capacity of 47 kDa. Search of the cloned sequences against GenBank
      revealed that Hq07 is a calreticulin (CRT)-similar clone and designated HqCRT.
      Expression analysis by reverse transcription-polymerase chain reaction showed
      that this gene is ubiquitously expressed at different developmental stages and in
      different tissues of H. qinghaiensis. The gene was expressed as glutathione S
      transferase-fused proteins in a prokaryotic system. Western blot analysis
      revealed that native HqCRT was secreted into their hosts by ticks during blood
      sucking. Vaccination of sheep with rHqCRT conferred protective immunity against
      ticks, resulting in 54.3% mortality in adult ticks, compared to the 38.7% death
      rate in the control group. These results demonstrated that rHqCRT might be a
      useful vaccine candidate antigen for biological control of H. qinghaiensis.

PMID- 18087724
TI  - Avian pelvis originates from lateral plate mesoderm and its development requires
      signals from both ectoderm and paraxial mesoderm.
AB  - The pelvic girdle is composed of three skeletal elements: ilium, pubis, and
      ischium. In comparison with other parts of the postcranial skeleton, its
      development is not well known to date. To elucidate the embryonic origin of the
      avian pelvic girdle and the signaling centers that control its development, we
      have performed extirpation and quail-to-chick grafting experiments. The results
      reveal that the entire pelvic girdle originates from the somatopleure at somite
      levels 26 to 35. No somitic cell contribution to skeletal elements of the pelvis
      has been detected. Removal of the surface ectoderm covering the lateral plate
      mesoderm has revealed that ectodermal signals control the development of the
      pelvic girdle, especially the formation of the pubis and ischium. The impaired
      development of the ischium and pubis correlates with the downregulation of Pax1
      and Alx4, two transcription factors that control the normal development of the
      ischium and pubis. Although of somatopleural origin, the development of the ilium
      depends on somitic signals. Insertion of a barrier between somites and
      somatopleure disrupts the expression of Emx2 and prevents normal development of
      the ilium but does not affect the expression of Pax1 or Alx4 and the development
      of the pubis and ischium. Thus, the development of the ilium, but not of the
      pubis and ischium, depends on somitic and ectodermal signals.

PMID- 18087725
TI  - Direct induction of layered tissues from mouse embryonic stem cells: potential
      for differentiation into urinary tract tissue.
AB  - The aim of this study was to induce organized layered tissues with
      characteristics of the urinary tract from embryonic stem (ES) cells alone. We
      seeded embryoid bodies (EBs) originating from mouse ES cells onto mono-layered
      collagen membranes and cultured them in four different media. Group 1 was grown
      in a mixed medium of keratinocyte serum-free medium (KSFM) and Medium 199, Group
      2 in a mixed medium of KSFM and conditioned medium collected from 3T3
      fibroblasts, Group 3 in an EB formation medium (control group), and Group 4 in
      KSFM only (control group). After 28 days, cultured tissues were transplanted into
      nude mice. Cultured tissues from Groups 1 and 2 formed four-layered structures
      comprising a stratified epithelium, a submucosal loose connective tissue layer, a
      smooth muscle cell layer identified immunohistochemically by alpha-smooth muscle
      actin, and a deep loose connective tissue layer identical to the adventitia.
      Immunohistochemistry showed that the epithelia were positive for cytokeratins.
      Tissues also expressed uroplakin as detected by reverse transcription/polymerase
      chain reaction. In contrast, specimens from Groups 3 and 4 demonstrated necrotic
      features. Uroplakin-positive (i.e., urothelium-like) cells developed only in
      Group 2 in the transplanted culture tissues in nude mice. In addition to inducing
      organized layered tissues from mouse ES cells directly in vitro, these findings
      demonstrate that tissues cultured in KSFM plus conditioned medium from 3T3
      fibroblasts differentiate into luminal walls similar to those of urinary tract in
      vivo. These findings suggest a new approach to urinary tract regeneration.

PMID- 18087726
TI  - Adhesion structures and their cytoskeleton-membrane interactions at podosomes of
      osteoclasts in culture.
AB  - The organization of the cytoskeleton in the podosomes of osteoclasts was studied
      by use of cell shearing, rotary replication, and fluorescence cytochemical
      techniques. After shearing, clathrin plaques and particles associated with the
      cytoskeleton were left behind on the exposed cytoplasmic side of the membrane.
      The cytoskeleton of the podosomes was characterized by two types of actin
      filaments: relatively long filaments in the portion surrounding the podosome
      core, and highly branched short filaments in the core. Individual actin filaments
      radiating from the podosomes interacted with several membrane particles along the
      length of the filaments. Many lateral contacts with the membrane surface by the
      particles were made along the length of individual actin filaments. The polarity
      of actin filaments in podosomes became oriented such that their barbed ends were
      directed toward the core of podosomes. The actin cytoskeletons terminated or
      branched at the podosomes, where the membrane tightly adhered to the substratum.
      Microtubules were not usually present in the podosome structures; however,
      certain microtubules appeared to be morphologically in direct contact with the
      podosome core. Most of the larger clathrin plaques consisted of flat sheets of
      clathrin lattices that interconnected neighboring clathrin lattices to form an
      extensive clathrin area. However, the small deeply invaginated clathrin plaques
      and the podosomal cytoskeleton were located close together. Thus, the clathrin
      plaques on the ventral membrane of osteoclasts might be involved in both cell
      adhesion and the formation of receptor-ligand complexes, i.e., endocytosis.

PMID- 18087727
TI  - Developmental regulation and functions of the expression of the neuropeptide
      corazonin in Drosophila melanogaster.
AB  - Although the corazonin gene (Crz) has been molecularly characterized, little is
      known concerning the function of this neuropeptide in Drosophila melanogaster. To
      gain insight into Crz function in Drosophila, we have investigated the
      developmental regulation of Crz expression and the morphology of corazonergic
      neurons. From late embryo to larva, Crz expression is consistently detected in
      three neuronal groups: dorso-lateral Crz neurons (DL), dorso-medial Crz neurons
      (DM), and Crz neurons in the ventral nerve cord (vCrz). Both the vCrz and DM
      groups die via programmed cell death during metamorphosis, whereas the DL neurons
      persist to adulthood. In adults, Crz is expressed in a cluster of six to eight
      neurons per lobe in the pars lateralis (DLP), in numerous neuronal cells in the
      optic lobes, and in a novel group of four abdominal ganglionic neurons present
      only in males (ms-aCrz). The DLP group consists of two subsets of cells having
      different developmental origins: embryo and pupa. In the optic lobes, we have
      detected both Crz transcripts and Crz promoter activity, but no Crz
      immunoreactive products, suggesting a post-transcriptional regulation of Crz
      mRNA. Projections of the ms-aCrz neurons terminate within the ventral nerve cord,
      implying a role as interneurons. Terminals of the DLP neurons are found in the
      retrocerebral complex that produces juvenile hormone and adipokinetic hormone.
      Significant reduction of trehalose levels in adults lacking DLP neurons suggests
      that DLP neurons are involved in the regulation of trehalose metabolism. Thus,
      the tissue-, stage-, and sex-specific expression of Crz and the association of
      Crz with the function of the retrocerebral complex suggest diverse roles for this
      neuropeptide in Drosophila.

PMID- 18087728
TI  - Molecular characterization and immunohistochemical localization of a novel
      troponin C during silkworm development.
AB  - We have cloned and sequenced a novel Bombyx mori gene that encodes a protein
      having a high degree of homology with other known troponin C (TnC) proteins. The
      amino acid sequence, DX[DN]X[DSG]X(6)E, a highly conserved putative Ca(2+) 
      binding motif found in loops within the globular domains of previously identified
      TnC proteins, is also present in BmTnC. We have expressed and purified to
      homogeneity a His-tagged BmTnC fusion protein having a molecular weight of
      approximately 21.6 kDa. We have used this purified fusion protein to produce
      polyclonal antibodies against BmTnC for Western blot analyses. These analyses
      have revealed that BmTnC is expressed in the larval head, the Malpighian tubule,
      the epidermis, the testis, and the gut, as has been confirmed by
      immunohistochemistry. In addition, real-time reverse transcription/polymerase
      chain reaction has shown that BmTnC mRNA levels differ substantially among these
      tissues. Our findings indicate that BmTnC is selectively expressed in the
      muscular tissues of the silkworm, including portions of the head, the Malpighian
      tubule, the body wall, and the gut.

PMID- 18087729
TI  - Environmental factors affecting feed intake of steers in different housing
      systems in the summer.
AB  - A total of 188 yearling steers of predominantly Angus and Hereford breeds, with
      mean body weight of 299 kg, were used in this study, which started on 8 April and
      finished on 3 October, to assess the effects of environmental factors on feed
      intake of steers in various housing systems. Housing consisted of outside lots
      with access to overhead shelter, outside lots with no overhead shelter and a cold
      confinement building. Ad libitum corn, 2.27 kg of 35% dry matter whole plant
      sorghum silage and 0.68 kg of a 61% protein-vitamin-mineral supplement was
      offered. Feed that was not consumed was measured to determine feed intake. The
      temperature data were recorded by hygro-thermographs. Hourly temperatures and
      humidity were used to develop weather variables. Regression analysis was used and
      weather variables were regressed on dry matter intake (DMI). When addition of a
      new variable did not improve R (2) more than one unit, then the number of
      variables in the model was truncated. Cattle in confinement had lower DMI than
      those in open lots and those in open lots with access to an overhead shelter (P <
      0.05). Cattle in outside lots with access to overhead shelter had similar DMI
      compared to those in open lots (P = 0.065). Effect of heat was predominantly
      displayed in August in the three housing systems. In terms of explaining
      variation in DMI, in outside lots with access to overhead shelter, average and
      daytime temperatures were important factors, whereas in open lots, nocturnal,
      peak and average temperatures were important factors. In confinement buildings,
      the previous day's temperature and humidity index were the most important factors
      explaining variation in DMI. Results show the effect of housing and weather
      variables on DMI in summer and when considering these results, cattle producers
      wishing to improve cattle feedlot performance should consider housing conditions
      providing less stress or more comfort.

PMID- 18087730
TI  - Molecular modeling and biophysical analysis of the c-MYC NHE-III1 silencer
      element.
AB  - G-Quadruplex and i-Motif-forming sequences in the promoter regions of several
      oncogenes show promise as targets for the regulation of oncogenes. In this study,
      molecular models were created for the c-MYC NHE-III(1) (nuclease hypersensitivity
      element III(1)) from two 39-base complementary sequences. The NHE modeled here
      consists of single folded conformers of the polypurine intramolecular G
      Quadruplex and the polypyrimidine intramolecular i-Motif structures, flanked by
      short duplex DNA sequences. The G-Quadruplex was based on published NMR
      structural data for the c-MYC 1:2:1 loop isomer. The i-Motif structure is
      theoretical (with five cytosine-cytosine pairs), where the central intercalated
      cytosine core interactions are based on NMR structural data obtained for a
      tetramolecular [d(A(2)C(4))(4)] model i-Motif. The loop structures are in silico
      predictions of the c-MYC i-motif loops. The porphyrin meso-tetra(N-methyl-4
      pyridyl)porphine (TMPyP4), as well as the ortho and meta analogs TMPyP2 and
      TMPyP3, were docked to six different locations in the complete c-MYC NHE.
      Comparisons are made for drug binding to the NHE and the isolated G-Quadruplex
      and i-Motif structures. NHE models both with and without bound cationic porphyrin
      were simulated for 100 ps using molecular dynamics techniques, and the non-bonded
      interaction energies between the DNA and porphyrins calculated for all of the
      docking interactions.

PMID- 18087731
TI  - Identification of new ANG gene mutations in a large cohort of Italian patients
      with amyotrophic lateral sclerosis.
AB  - Angiogenin (ANG) gene, coding for an angiogenic factor up-regulated by hypoxia
      and expressed in ventral horn motor neurons, is a novel candidate for the
      pathogenesis of amyotrophic lateral sclerosis (ALS). ALS is a fatal
      neurodegenerative disease characterized by the selective loss of cortical and
      spinal motor neurons. Missense mutations in ANG gene have been identified in two
      ALS populations from Northern Europe and North America, both in familial (FALS)
      and sporadic (SALS) patients, but they do not seem to be frequent in the Italian
      population. We performed a mutational screening in a large cohort of 737 Italian
      ALS patients, including 605 SALS and 132 FALS cases. We identified seven
      different mutations, five of which are novel, in nine patients (six SALS and
      three FALS), but not in 515 healthy controls. Three mutations are located in the
      signal peptide region, three in the coding sequence, and one in the 3'
      untranslated region. In our ALS population, the observed mutational frequency of
      ANG gene accounts for about 1.2%, with an overrepresentation of FALS (2.3%)
      compared to SALS (1%) cases. We also found the previously described I46V
      substitution in six patients and four controls, suggesting that this mutation may
      represent a benign variant, at least in the Italian population. Our results
      provide further evidence of a tight link between angiogenesis and ALS
      pathogenesis and suggest that mutations in ANG gene are associated with an
      increased risk to develop ALS.

PMID- 18087732
TI  - Evidence of means-end behavior in Asian elephants (Elephas maximus).
AB  - The present study explores to what extent Asian elephants show "means-end"
      behavior. We used captive Asian elephants (N = 2) to conduct four variations of
      the Piagetian "support" problem, which involves a goal object that is out of
      reach, but rests on a support within reach. In the first condition, elephants
      were simultaneously presented with two identical trays serving as the "support",
      with the bait on one tray and the other tray left empty. In the next two
      conditions, the bait was placed on one tray, while additional bait was placed
      beside the other tray. In the last condition, both trays contained bait, but one
      of the trays had a small gap which prevented the elephants from reaching the
      reward. Subjects were required to choose and pull either tray with their trunk
      and to obtain the bait (i.e. goal). Results showed that one elephant performed
      all of the support problems significantly above chance after several sessions,
      suggesting that the elephant was capable of understanding that pulling the tray
      was the "means" for achieving the "end" of obtaining the bait. This study showed
      that elephants show means-end behavior when subjected to a Piagetian "support"
      task, and indicates that such goal-directed behavior occurs in species other than
      primates.

PMID- 18087734
TI  - The presence of infectious extracellular Francisella tularensis subsp. novicida
      in murine plasma after pulmonary challenge.

PMID- 18087733
TI  - Pneumococcal serology in children's respiratory infections.
AB  - The role of Streptococcus pneumoniae in the etiology of respiratory tract
      infections has been studied serologically using microbe-specific antibody and
      immune complex assays. Serological methods are sensitive in the bacteremic
      pneumococcal pneumonia of adults. In children, however, pneumococcal pneumonia is
      seldom bacteremic, and, thus, in the absence of a gold standard for the detection
      of pneumococcal infection, serological methods are still insufficiently
      validated. We report here indirect evidence for the sensitivity and specificity
      of pneumococcal serology in children. Serological evidence of pneumococcal
      infection has been found in 27% to 38% of children with radiologically confirmed
      pneumonia, in 7% to 8% of children with viral wheezy bronchitis, and in <1% to 5%
      of children and young adults with viral upper respiratory infection. Serological
      findings for pneumococcal infection have been dependent on the study venue,
      whether in hospital or ambulatory subjects, and on the test panel used. Where
      both antibody and immune complex assays have been available, the proportion of
      children with pneumococcal infection has been 32% to 37% in inpatients and 27% to
      28% in outpatients. The respective rates have been 10% to 18% by antibody assays
      alone. Pneumococcal acute otitis media, when present with pneumonia, may confound
      findings in pneumococcal serology, but pure nasopharyngeal carriage of S.
      pneumoniae has little effect. In contrast, carriage acquisition of a new serotype
      may induce significant antibody production. Thus, understandably, significant
      rises between paired sera in antibodies to pneumococcal capsular polysaccharides
      and pneumococcal pneumolysin have been found in <1% to 3% of non-symptomatic
      children and young adults. Findings from the last 20 years indirectly suggest
      that pneumococcal antibody and immune complex assays are sensitive and specific
      enough for the detection of pneumococcal infection in children. However, the
      methods are too complex for routine clinical practice, and, so far, serological
      methods for S. pneumoniae infections have only been used for research purposes.

PMID- 18087735
TI  - Utility of direct, real-time PCR in the management of a nosocomial outbreak of
      vancomycin-resistant Enterococcus faecium (vanB genotype).

PMID- 18087736
TI  - Physiological aggregation of maltodextrin phosphorylase from Pyrococcus furiosus
      and its application in a process of batch starch degradation to alpha-D-glucose-1
      phosphate.
AB  - Maltodextrin phosphorylase from Pyrococcus furiosus (PF1535) was fused with the
      cellulose-binding domain of Clostridium cellulovorans serving as an aggregation
      module. After molecular cloning of the corresponding gene fusion construct and
      controlled expression in Escherichia coli BL21, 83% of total maltodextrin
      phosphorylase activity (0.24 U/mg of dry cell weight) was displayed in active
      inclusion bodies. These active inclusion bodies were easily isolated by nonionic
      detergent treatment and directly used for maltodextrin conversion to alpha-D
      glucose-1-phosphate in a repetitive batch mode. Only 10% of enzyme activity was
      lost after ten conversion cycles at optimum conditions.

PMID- 18087737
TI  - Recovery of plant growth-promoting rhizobacteria from sodium alginate beads after
      3 years following storage at 4 degrees C.
AB  - Two plant growth-promoting bacteria, Bacillus subtilis and Pseudomonas corrugata,
      immobilized in a sodium alginate based formulation were evaluated for their
      survival, viability and plant growth-promoting ability after 3 years of storage
      at 4 degrees C. Populations of both of the bacterial isolates recovered from the
      immobilized sodium alginate beads were in the order of 10(8) cfu g(-1). The plant
      based bioassay indicated that the plant growth promotion ability of both of the
      bacterial isolates was equal to those of fresh broth-based formulations. The
      bacterial isolates retained the root colonization, and antifungal and enzyme
      activities in the alginate-based formulation during storage.

PMID- 18087738
TI  - Scale-up fermentation of recombinant Candida rugosa lipase expressed in Pichia
      pastoris using the GAP promoter.
AB  - The high-cell-density fermentation of Candida rugosa lipase in the constitutive
      Pichia pastoris expression system was scaled up from 5 to 800 l in series by
      optimizing the fermentation conditions at both lab scale and pilot scale. The
      exponential feeding combined with pH-stat strategy succeeded in small scale
      studies, while a two-stage fermentation strategy, which shifted at 48 h by fine
      tuning the culture temperature and pH, was assessed effective in pilot-scale
      fermentation. The two-stage strategy made an excellent balance between the
      expression of heterogeneous protein and the growth of host cells, controlling the
      fermentation at a relatively low cell growth rate for the constitutive yeast
      expression system to accumulate high-level product. A stable lipase activity of
      approximately 14,000 IU ml(-1) and a cell wet weight of ca. 500 g l(-1) at the
      800-l scale were obtained. The efficient and convenient techniques suggested in
      this study might facilitate further scale-up for industrial lipase production.

PMID- 18087739
TI  - High resolution SE-fMRI in humans at 3 and 7 T using a motor task.
AB  - OBJECT: The sensitivity of spin echo (SE) experiments to blood oxygenation level
      dependent (BOLD) contrast was explored in a study of the same six subjects
      carried out at 3 and 7 T. MATERIALS AND METHODS: Multi-slice, single shot, spin
      echo, echo planar images with a voxel size of 1 x 1 x 3 mm3 were acquired at
      three different echo times, during execution of a simple motor task. RESULTS:
      Significant activation was observed at all echo times at both field strengths.
      Analysis of the fractional signal change as a function of echo time indicated
      that the change in relaxation rate, Delta R2, at 7 T was -0.51 +/- 0.14 s (-1),
      which was 1.3 times larger than the value found at 3 T. Measurements of the
      percentage signal change on activation and temporal signal to noise ratio showed
      that there was an increase in the BOLD contrast to noise ratio (CNR) at 7 versus
      3 T by a factor of 1.9. There was no overlap of areas of significant activation
      in the SE data acquired at either field strength with the site of large veins.
      CONCLUSION: SE-BOLD CNR in motor cortex was found to increase significantly at 7
      T compared with 3 T.

PMID- 18087740
TI  - Experiences with a new health scoring system for treks.

PMID- 18087741
TI  - Lessons in hypoxic adaptation from high-altitude populations.
AB  - An increase in hemoglobin level is seen in virtually all lowlanders who move to
      or train at altitude; however, studies of high-altitude native populations
      illustrate that this response is not necessary for successful long-term
      residence. Indigenous populations living at the same altitude have differences
      not only in hemoglobin level but also in other traits like oxygen saturation.
      Support for a genetic causation for differences in features of oxygen transport,
      namely hemoglobin levels and oxygen saturation, is derived from kindred studies
      among the highlander populations. Indeed, evidence from Tibet suggests that
      inferred genes for high oxygen saturation are associated with higher offspring
      survival. It may be that signaling molecules like nitric oxide and transcription
      factors such as hypoxia-inducible factor could act as an upstream regulator for
      highlander traits. However, the preponderance of data suggests that it is
      unlikely that one process or even a common set of processes is responsible for
      successful biologic adaptation shown in all three resident high-altitude
      populations. Future studies will require the ability to identify combinations of
      genetic variants with outcomes including expression levels, appropriate
      phenotypes, and functional responses.

PMID- 18087742
TI  - Ambulatory measurement of shoulder and elbow kinematics through inertial and
      magnetic sensors.
AB  - Inertial and magnetic measurement systems (IMMSs) are a new generation of motion
      analysis systems which may diffuse the measurement of upper-limb kinematics to
      ambulatory settings. Based on the MT9B IMMS (Xsens Technologies, NL), we
      therefore developed a protocol that measures the scapulothoracic, humerothoracic
      and elbow 3D kinematics. To preliminarily evaluate the protocol, a 23-year-old
      subject performed six tasks involving shoulder and elbow single-joint-angle
      movements. Criteria for protocol validity were limited cross-talk with the other
      joint-angles during each task; scapulohumeral-rhythm close to literature results;
      and constant carrying-angle. To assess the accuracy of the MT9B when measuring
      the upper-limb kinematics through the protocol, we compared the MT9B estimations
      during the six tasks, plus other four, with the estimations of an optoelectronic
      system (the gold standard), in terms of RMS error, correlation coefficient (r),
      and the amplitude ratio (m). Results indicate that the criteria for protocol
      validity were met for all tasks. For the joint angles mainly involved in each
      movement, the MT9B estimations presented RMS errors <3.6 degrees , r > 0.99 and
      0.9 < m < 1.09. It appears therefore that (1) the protocol in combination with
      the MT9B is valid for, and (2) the MT9B in combination with the protocol is
      accurate when, measuring shoulder and elbow kinematics, during the tasks tested,
      in ambulatory settings.

PMID- 18087743
TI  - An interactive Internet-based system for tracking upper limb motion in home-based
      rehabilitation.
AB  - In this paper, we introduce an interactive telecommunication system that supports
      video/audio signal acquisition, data processing, transmission, and 3D animation
      for post stroke rehabilitation. It is designed for stroke patients to use in
      their homes. It records motion exercise data, and immediately transfers this data
      to hospitals via the internet. A real-time videoconferencing interface is adopted
      for patients to observe therapy instructions from therapists. The system uses a
      peer-to-peer network architecture, without the need for a server. This is a
      potentially effective approach to reducing costs, allowing easy setup and
      permitting group-rehabilitation sessions. We evaluate this system using the
      following steps: (1) motion detection in different movement patterns, such as
      reach, drink, and reach-flexion; (2) online bidirectional visual
      telecommunication; and (3) 3D rendering using a proposed offline animation
      package. This evaluation has subjectively been proved to be optimal.

PMID- 18087744
TI  - Joint application of rough set-based feature reduction and Fuzzy LS-SVM
      classifier in motion classification.
AB  - This paper presents an effective classification scheme consisting of the rough
      set theory (RST)-based feature selection and the fuzzy least squares support
      vector machine (LS-SVM) classifier for the surface electromyographic (sEMG)-based
      motion classification. The wavelet packet transform (WPT) is exploited to
      decompose the four-class motion EMG signals to the non-overlapped sub-bands and
      the energy characteristic of each sub-band is adopted to form the original
      feature set. In order to reduce the computation complexity, the RST is utilized
      to get the reduction feature set without compromising classification accuracy. In
      the feature reduction phase, cluster separation index (CSI) is introduced to
      evaluate the performance of the proposed algorithm. In the sequel, the Fuzzy LS
      SVM is constructed for the multi-class classification task. The RST-based feature
      selection is independent of the classifier design. Consequently the
      classification performance will vary with different classifiers. We make the
      comparison between the proposed classification scheme and the commonly used
      classification scheme, such as the combination of the principal component
      analysis (PCA)-based feature selection and the neural network (NN) classifier.
      The results of comparative experiments show that the diverse motions can be
      identified with high accuracy by the proposed scheme. Compared with other feature
      extraction and selection algorithms and classifiers, superior performance of the
      proposed classification scheme illustrates the potential of the SVM techniques
      combined with WPT and RST in EMG motion classification.

PMID- 18087745
TI  - Artifact removal and texture-based rendering for visualization of 3D fetal
      ultrasound images.
AB  - Convenient and non-invasive ultrasonography has become an essential tool for
      diagnosing fetal abnormalities. However, the noisy and blurry nature of
      sonographic data poses a challenge. To improve object visualization, we first
      develop a modified diffusion filter that utilizes the local standard deviation
      and edge of local-average-difference to define an adaptive edge stopping function
      in diffusion filtering. The proposed method overcomes the drawbacks of
      traditional diffusion filters and shows good results in comparative experiments.
      Moreover, we propose a novel light absorbing function to remove large regions of
      interface artifacts. An advanced imaging mode, called texture-based rendering, is
      employed to provide more realistic rendering. Experimental results show that the
      proposed methods enhance final image quality in 3D fetal sonograms.

PMID- 18087746
TI  - Imaging features suggestive of a conjoined nerve root on routine axial MRI.
AB  - OBJECTIVE: The purpose of our study is to evaluate imaging features suggestive of
      a conjoined nerve root on routine axial MRI. METHODS: Two radiologists and two
      surgeons retrospectively reviewed the MRI of three cases in which a conjoined
      nerve root was discovered during operation and found three suggestive signs on
      routine axial MR images: "corner" (asymmetric morphology of the anterolateral
      corner of the dural sac), "fat crescent" (intervening extradural fat between the
      asymmetric dura and the nerve root), and "parallel" signs (visualization of the
      entire parallel course of the nerve root at the disc level). Two radiologists
      prospectively found these signs during routine MRI interpretation sessions over a
      period of 6 months. If one or a combination of signs were noted on axial MR
      images, contiguous axial scans were additionally obtained. Three cases that were
      previously found during operations were also included. Prevalence and confidence
      scores for each sign were assessed on axial T1- and T2-weighted images. RESULTS:
      Twelve patients showed one or a combination of the three signs, 9 had contiguous
      axial MR scans. Five cases were confirmed by operation. The prevalence of the
      corner, fat crescent, and parallel signs were 12 out of 12 (100%), 6 out of 12
      (50%), and 8 out of 12 (67.7%) on axial T1-weighted images. The overall
      diagnostic confidence was higher on T1- than on T2-weighted images (P<0.05).
      CONCLUSION: On routine axial L-spine MRI, corner, fat crescent, and parallel
      signs are suggestive of and assist in the recognition of a conjoined nerve root.

PMID- 18087747
TI  - Diagnostic accuracy of plain radiographs and cineradiography in diagnosing
      traumatic scapholunate dissociation.
AB  - OBJECTIVE: Missed tears of the scapholunate ligament (SLL) and scapholunate
      dissociation (SLD) after wrist injuries pose a high risk of post-traumatic
      osteoarthritis of the carpus. Plain X-rays and dynamic radiographic studies are
      frequently used for initial diagnostic work-up. Given the limited evidence of
      their accuracy, we retrospectively compared the radiographic findings of patients
      with suspected traumatic SLD with wrist arthroscopy as the accepted reference
      standard. DESIGN AND METHODS: During a 6-year period, plain radiographs and DSA
      cineradiography scans were obtained from 198 patients who had sustained a
      hyperextension injury to their hand. Of those, 102 (72 men, 30 women, mean age of
      42+/-12 years) subsequently underwent diagnostic arthroscopy. Digital images were
      reevaluated by experienced radiologists unaware of the arthroscopic findings for
      the presence or absence of SLD. We calculated the sensitivity (SN) and
      specificity (SP) with 95% confidence intervals (CI), and computed areas under the
      receiver operating characteristic curves (AUC/ROC). RESULTS: Arthroscopy revealed
      42 SLL ruptures, 13, 10, and 19 of which were classified as grade I (partial), II
      (complete with dynamic instability), or III (complete with static instability)
      respectively. Plain radiographs correctly identified 24 injuries (SN 57.1%, 95%
      CI 41.0-72.3%), and produced 1 false-positive result (SP 98.3%, 95% CI 91.1
      100.0%). The scapholunate distance and the SL angle contributed independently to
      the diagnostic variance, with an AUC/ROC of 85.7% (95% CI 76.8-92.2%).
      Cineradiography had a sensitivity of 36 out of 42 (85.7%, 95% CI 71.5-94.6%), and
      a specificity of 57 out of 60 (95.0%, 95% CI 86.1-99.0%). CONCLUSION:
      Pathological results on plain radiographs and cineradiography reliably indicate
      the presence of SLD after wrist trauma. Although non-conclusive, a negative
      dynamic study markedly reduces the pre-test probability of disease. Both methods
      remain key elements of primary diagnostic strategies for suspected traumatic SLD,
      and may facilitate the selection of additional tests.

PMID- 18087748
TI  - Baastrup's disease (kissing spine) demonstrated by FDG PET/CT.
AB  - 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG
      PET/CT) is a widely used imaging modality in cancer patients. However, there are
      many potential non-neoplastic causes of FDG uptake. We report a case of FDG
      uptake between the spinous processes, secondary to Baastrup's disease. Knowledge
      of this pattern of uptake is helpful in diagnosing Baastrup's disease and
      avoiding false-positive diagnoses.

PMID- 18087750
TI  - Towards theoretical formalisms.

PMID- 18087751
TI  - How can evolutionary theory accommodate recent empirical results on organismal
      senescence?
AB  - According to a prominent recent report, guppies collected from sites lacking
      predators are inferior in every aspect of their life history profile to those
      evolved in other, nearby sites with predators present. This is an exception to
      two classical predictions of evolutionary theory: that low extrinsic mortality
      should be associated with longer life span, and that higher fertility should be
      associated with shorter life span. Some theorists have tried to accommodate this
      and other anomalous results within the standard framework, but we argue that the
      exceptions they carve out do not explain the results at hand. In fact, the
      findings suggest that population regulation has been selected at the group level,
      though this is a mechanism that most theorists regard with suspicion. We conclude
      by relating the present result to other experiments that seem to point in the
      same direction.

PMID- 18087752
TI  - Evolution of the vertebrate Y RNA cluster.
AB  - Relatively little is known about the evolutionary histories of most classes of
      non-protein coding RNAs. Here we consider Y RNAs, a relatively rarely studied
      group of related pol-III transcripts. A single cluster of functional genes is
      preserved throughout tetrapod evolution, which however exhibits clade-specific
      tandem duplications, gene-losses, and rearrangements.

PMID- 18087753
TI  - Spectral plots and the representation and interpretation of biological data.
AB  - It is basic question in biology and other fields to identify the characteristic
      properties that on one hand are shared by structures from a particular realm,
      like gene regulation, protein-protein interaction or neural networks or foodwebs,
      and that on the other hand distinguish them from other structures. We introduce
      and apply a general method, based on the spectrum of the normalized graph
      Laplacian, that yields representations, the spectral plots, that allow us to find
      and visualize such properties systematically. We present such visualizations for
      a wide range of biological networks and compare them with those for networks
      derived from theoretical schemes. The differences that we find are quite striking
      and suggest that the search for universal properties of biological networks
      should be complemented by an understanding of more specific features of
      biological organization principles at different scales.

PMID- 18087754
TI  - Neurosemantics, neurons and system theory.
AB  - Following the concept of internal representations, signal processing in a
      neuronal system has to be evaluated exclusively based on internal system
      characteristics. Thus, this approach omits the external observer as a control
      function for sensory integration. Instead, the configuration of the system and
      its computational performance are the effects of endogenous factors. Such self
      referential operation is due to a strictly local computation in a network and,
      thereby, computations follow a set of rules that constitute the emergent
      behaviour of the system. These rules can be shown to correspond to a "logic" that
      is intrinsic to the system, an idea which provides the basis for neurosemantics.

PMID- 18087755
TI  - The mitochondrial DNA of Xenoturbella bocki: genomic architecture and
      phylogenetic analysis.
AB  - The phylogenetic position of Xenoturbella bocki has been a matter of controversy
      since its description in 1949. We sequenced a second complete mitochondrial
      genome of this species and performed phylogenetic analyses based on the amino
      acid sequences of all 13 mitochondrial protein-coding genes and on its gene
      order. Our results confirm the deuterostome relationship of Xenoturbella.
      However, in contrast to a recently published study (Bourlat et al. in Nature
      444:85-88, 2006), our data analysis suggests a more basal branching of
      Xenoturbella within the deuterostomes, rather than a sister-group relationship to
      the Ambulacraria (Hemichordata and Echinodermata).

PMID- 18087756
TI  - Problems with the current deinococcal hypothesis: an alternative theory.
AB  - All theories related to the evolution of Deinococcus radiodurans have a common
      denominator: the strong positive correlation between ionizing-radiation
      resistance and desiccation tolerance. Currently, the widespread hypothesis is
      that D. radiodurans' ionizing-radiation resistance is a consequence of this
      organism's adaptation to desiccation (desiccation adaptation hypothesis). Here,
      we draw attention to major discrepancy that has emerged between the "desiccation
      adaptation hypothesis" and recent findings in computational biology, experimental
      research, and terrestrial subsurface surveys. We explain why the alternative
      hypothesis, suggesting that D. radiodurans' desiccation tolerance could be a
      consequence of this organism's adaptation to ionizing radiation (radiation
      adaptation hypothesis), should be considered on equal basis with the "desiccation
      adaptation hypothesis".

PMID- 18087757
TI  - Why are diploid genomes widespread and dominant mutations rare?
AB  - We have used the sexual Penna ageing model to show that the relation between
      dominance and recessiveness could be a force which optimizes the genome size.
      While the possibility of complementation of the damaged allele by its functional
      counterparts (recessiveness) leads to the redundancy of genetic information, the
      dominant effect of defective genes tends to diminish the number of alleles
      fulfilling the same function. Playing with the fraction of dominant loci in the
      genome it is possible to obtain the condition where the diploid state of the
      genome is optimal. If the status of each bit position as dominant or recessive
      mutations is changed for each individual randomly and rarely, then after a long
      time a stationary equilibrium of many recessive and few dominant loci is
      established in the sexual Penna model. This effect vanishes if the same changing
      distribution of dominant loci applies to all individuals.

PMID- 18087758
TI  - Sympatric speciation as intrinsic property of the expanding population.
AB  - Sympatric speciation is still debatable, though some well documented empirical
      data that support it already exist. Our computer modeling reveals that sympatric
      speciation is an intrinsic property of the expanding populations with
      differentiated inbreeding-higher at the edges and lower inside the territory. At
      the edges of expanding populations, the probability of forming deleterious
      phenotypes by placing two defective alleles in the corresponding loci is
      relatively high even with low genetic load. Thus, the winning strategy is to use
      rather the complementary haplotypes to form zygotes. This strategy leads to a
      very fast sympatric speciation and specific distribution of recombination
      activity along the chromosomes-higher at the subtelomeric regions (close to the
      ends of chromosomes) and lower in the middle of chromosomes, which is also
      observed in all human chromosomes (excluding Y).

PMID- 18087759
TI  - Towards understanding the immune system.
AB  - It is proposed that using both self-non-self and danger theories give a better
      understanding of how the immune system works. It is proposed that comparing the
      immune system to the police force is useful in this case since the police respond
      both to danger or damage signals and foreign or suspicious behavior even if no
      danger signals existed. We also propose that due to low zone tolerance,
      immunotherapy needs to be combined with another treatment method for cancer,
      e.g., chemotherapy or/and radiotherapy, to get sufficient eradication of tumors.
      Finally, we propose that fractional order differential equations are more
      suitable than the familiar integer order differential equations. A fractional
      order example of two immune effectors attacking an antigen is given.

PMID- 18087761
TI  - Anticitrulline peptide antibodies (CCP3) in leprosy sera: a negative association.
AB  - Anticyclic citrullinated peptide antibodies (anti-CCP) have been described almost
      exclusively in patients with rheumatoid arthritis. Recently, these autoantibodies
      have been found in patients with active tuberculosis. Leprosy is another
      mycobacterial disease where the presence of autoantibodies has been described by
      several authors. In this study, 64 patients with leprosy (32 paucibacillary and
      32 multibacillary forms of the disease) were evaluated and only 2 patients were
      positive for the presence of anti-CCP. The low frequency of anti-CCP in leprosy
      sera demonstrated in our study illustrates the high specificity of anti-CCP for
      the diagnosis of rheumatoid arthritis.

PMID- 18087763
TI  - Unusual case of camptocormia triggered by lumbar-disc herniation.
AB  - A 21-year-old male patient with low back pain and marked forward bending was
      presented. The exaggerated lumbar flexion was preventing him to stand in erect
      posture but disappeared while lying. The symptoms had begun after he had lifted a
      heavy object. Straight-leg-raising test could not be performed properly because
      of the exaggerated pain. The light-touch sense was decreased on L5 and S1
      dermatomes. There was no loss of muscle strength. The deep-tendon reflexes were
      normal. Plain graph showed mild narrowing in the L4-5 and L5-S1 intervertebral
      spaces. Lumbar magnetic resonance imaging revealed disc protrusions in L4-5 and
      L5-S1 levels. During his stay in the department, the patient was given tizanidine
      and tramadol, and physical therapy was performed. A paravertebral intramuscular
      injection with lidocaine was applied. Moreover, the patient was referred to
      psychiatrist for evaluation regarding his medical history of conversive seizures
      and possible efforts for secondary gain. No response was obtained from all the
      treatments. The final diagnosis was camptocormia triggered by lumbar-disc
      herniation. He was applied supportive psychotherapy, psychoeducation regarding
      secondary gain, strong suggestions to improve posture, positive reinforcement,
      and behavioral therapy. His postural abnormality resolved and disappeared
      completely with mild pain.

PMID- 18087760
TI  - Gene and genon concept: coding versus regulation. A conceptual and information
      theoretic analysis of genetic storage and expression in the light of modern
      molecular biology.
AB  - We analyse here the definition of the gene in order to distinguish, on the basis
      of modern insight in molecular biology, what the gene is coding for, namely a
      specific polypeptide, and how its expression is realized and controlled. Before
      the coding role of the DNA was discovered, a gene was identified with a specific
      phenotypic trait, from Mendel through Morgan up to Benzer. Subsequently, however,
      molecular biologists ventured to define a gene at the level of the DNA sequence
      in terms of coding. As is becoming ever more evident, the relations between
      information stored at DNA level and functional products are very intricate, and
      the regulatory aspects are as important and essential as the information coding
      for products. This approach led, thus, to a conceptual hybrid that confused
      coding, regulation and functional aspects. In this essay, we develop a definition
      of the gene that once again starts from the functional aspect. A cellular
      function can be represented by a polypeptide or an RNA. In the case of the
      polypeptide, its biochemical identity is determined by the mRNA prior to
      translation, and that is where we locate the gene. The steps from specific, but
      possibly separated sequence fragments at DNA level to that final mRNA then can be
      analysed in terms of regulation. For that purpose, we coin the new term "genon".
      In that manner, we can clearly separate product and regulative information while
      keeping the fundamental relation between coding and function without the need to
      introduce a conceptual hybrid. In mRNA, the program regulating the expression of
      a gene is superimposed onto and added to the coding sequence in cis - we call it
      the genon. The complementary external control of a given mRNA by trans-acting
      factors is incorporated in its transgenon. A consequence of this definition is
      that, in eukaryotes, the gene is, in most cases, not yet present at DNA level.
      Rather, it is assembled by RNA processing, including differential splicing, from
      various pieces, as steered by the genon. It emerges finally as an uninterrupted
      nucleic acid sequence at mRNA level just prior to translation, in faithful
      correspondence with the amino acid sequence to be produced as a polypeptide.
      After translation, the genon has fulfilled its role and expires. The distinction
      between the protein coding information as materialised in the final polypeptide
      and the processing information represented by the genon allows us to set up a new
      information theoretic scheme. The standard sequence information determined by the
      genetic code expresses the relation between coding sequence and product. Backward
      analysis asks from which coding region in the DNA a given polypeptide originates.
      The (more interesting) forward analysis asks in how many polypeptides of how many
      different types a given DNA segment is expressed. This concerns the control of
      the expression process for which we have introduced the genon concept. Thus, the
      information theoretic analysis can capture the complementary aspects of coding
      and regulation, of gene and genon.

PMID- 18087762
TI  - Evaluation of lateral instability of the atlanto-axial joint in rheumatoid
      arthritis using dynamic open-mouth view radiographs.
AB  - Upper cervical involvement is common in patients with rheumatoid arthritis (RA).
      Anterior atlanto-axial subluxation (aAAS) sometimes occurs at an early stage of
      the disease. We hypothesized that not only antero-posterior instability but
      lateral instability may occur with atlanto-axial involvement in RA. To prove this
      hypothesis, we evaluated the lateral instability of the atlanto-axial joint in
      RA, using dynamic open-mouth view radiographs. Thirty RA patients and a control
      group of 22 non-RA outpatients were enrolled in this study. The patients
      underwent lateral view radiographs of the cervical spine during flexion and
      extension, and antero-posterior (AP) open-mouth views during maximum right and
      left bending of the neck. The anterior atlanto-dental interval (AADI) was
      measured to evaluate antero-posterior instability of the atlanto-axial joint, and
      atlanto-dental lateral shift (ADLS) was defined to evaluate dynamic lateral
      instability. In the RA group, AADI averaged 3.2 mm in flexion, and in eight
      patients, it exceeded 3 mm in flexion (aAAS). In the control group, the AADI
      averaged 1.0 mm in flexion. The ADLS in the RA group averaged 14.8%, and this was
      significantly greater than in the control group, in which it averaged 6.1%. The
      ADLS averaged 20.6% in the RA subgroup with aAAS, and 12.7% in the RA subgroup
      without aAAS. In both subgroups, the ADLS was significantly greater than that of
      the control group. In this study, dynamic lateral instability of the atlanto
      axial joint in RA was demonstrated. The results suggest that an evaluation of the
      dynamic lateral instability of the atlanto-axial joint can be useful for early
      diagnosis of atlanto-axial lesions in RA.

PMID- 18087764
TI  - In vitro preliminary study to evaluate the capability of Er,Cr:YSGG laser in
      posterior teeth root-canal preparation with step-back technique.
AB  - This preliminary study was to investigate in vitro the Er,Cr:YSGG laser ablation
      capability, both range (enlargement aspects of laser tips corresponded to
      conventional endodontic files) and quality (removing of smear layer and opening
      of dentinal tubules) to clean and shape the root canal for final obturation step.
      The crowns of 15 extracted multi-rooted posterior human teeth were resected, and
      then 15 canals were prepared by an Er,Cr:YSGG laser up to 1.5 W (actual power
      output) using the step-back technique, while the other 15 canals (control) were
      enlarged conventionally by K-flex file. The results revealed that posterior root
      canal preparation could be achieved by laser beam transmitted to the canal using
      endodontic tips. At a chosen significance level of alpha = 1%, the results showed
      no significant statistical difference between the two groups (P > 0.01).
      Considering the results of this current study, laser-based root-canal preparation
      still shows certain limitations, and further improvements are mandatory for
      higher achievement and better preparation outcomes.

PMID- 18087766
TI  - Is level IIb lymph node dissection always necessary in N1b papillary thyroid
      carcinoma patients?
AB  - INTRODUCTION: Papillary thyroid carcinoma (PTC) patients show a high rate of
      cervical lymphatic metastasis. However, there are no universal binding guidelines
      for the extent of lateral cervical lymph node dissection (LND) in such cases. In
      particular, the need for LND above the spinal accessory nerve (SAN) remains
      controversial. The present study examined whether level IIb lymph node (LN)
      dissection is always necessary in PTC patients with lateral cervical LN
      metastasis. MATERIALS AND METHODS: The study prospectively examined 167 PTC
      patients with lateral cervical LN metastasis who underwent modified radical neck
      dissection (MRND) in our institution from November 2005 to March 2007. The MRND
      was bilateral in 24 cases. All patients underwent level II, III, IV, and V LND.
      Levels IIa and IIb LNs were individually dissected in all cases. All LND was
      performed using strict leveling criteria by a single operating team. The patterns
      of lymphatic metastasis and potential risk factors for level IIb LN involvement
      were evaluated. RESULTS: The most common site of metastasis was level III (80.6%
      of cases), followed by level IV (74.9%) and II (55.5%). The metastasis rates in
      level IIa and IIb were 55.5% and 6.8%, respectively; all level IIb LN metastasis
      was accompanied by level IIa metastasis (p=0.001). In addition, level IIb LN
      metastasis was found to be associated with the aggressiveness of lymphatic
      metastasis (i.e., the total number of metastatic LNs) (p<0.0001). CONCLUSIONS: A
      level IIb LND should be performed when there is clinical or radiological evidence
      of lymphatic metastasis. In the absence of such evidence, the findings suggest
      that level IIb LND is not necessary in N1b PTC patients when there is no level
      IIa LN metastasis, or when the metastasis is not aggressive.

PMID- 18087765
TI  - Stroke unit care: recurrence, mortality and institutionalisation rates-a four
      year follow-up study.
AB  - BACKGROUND: he benefits of stroke unit care in terms of reducing mortality,
      morbidity and the need for institutional care in the short term are clear. Less
      evidence exists of its longer term benefits. AIM: The aim of this study was to
      measure the rates of mortality, institutionalisation and stroke recurrence over
      a4-year period following stroke unit care. METHODS: Discharge and 4-year follow
      up data were examined on all patients admitted to the Stroke Rehabilitation Unit
      between September 2000 and August 2002. There results were compared with
      previously published data. RESULTS: After 4 years 8% of patients had sustained
      are current stroke, 40% were deceased and 40% were in institutional care.
      CONCLUSIONS: Compared to international data care at our unit appears to be
      associated with a lower rate of recurrent stroke and mortality but a higher
      institutionalisation rate after 4 years. The reasons for this are unclear.

PMID- 18087767
TI  - Aneurysm Sac pressure measurement with minimally invasive implantable pressure
      sensors: an alternative to current surveillance regimes after EVAR?
AB  - Current protocols for surveillance after endovascular repair (EVAR) of abdominal
      aortic aneurysms are mostly based on costly and time-consuming imaging procedures
      and aim to detect adverse events such as graft migration, endoleaks or aneurysm
      sac enlargement. These imaging procedures are either associated with radiation
      exposure to the patients or may be harmful to the patient due to the use of
      iodine- or gadolinium-containing contrast agents. Furthermore the advantages of
      EVAR in the short term might be negated by the necessity for endograft
      surveillance over years. Thus, alternative modalities for follow-up are being
      investigated. One of these technologies provides pressure information directly
      from the aneurysm sac. This noninvasive, telemetric pressure sensing was tested
      in vitro as well as in first clinical trials and was able to identify successful
      aneurysm exclusion after EVAR. The telemetric pressure sensors showed a promising
      efficacy and accuracy in detecting type I and type III endoleaks and will help to
      clarify the clinical relevance of type II endoleaks. This article provides an
      overview of the in vitro sensors investigated as well as the first clinical
      trials and the sensors' potential to change the current endograft surveillance
      regimes.

PMID- 18087769
TI  - Proceedings from the International Symposium: Cannabinoids as New Tools for the
      Treatment of Neurological Disorders, March 2006, Madrid, Spain.

PMID- 18087770
TI  - Proceedings of the meetings of the Environmental Neurology Club, Paris, France, 2
      3 December 2005 and Metz, France, 7 February 2007.

PMID- 18087771
TI  - Professionalism, Diversity, and Health Disparities. Proceedings of the J. Robert
      Gladden Orthopaedic Society Inaugural Meeting, July 6-10, 2006, Lausanne,
      Switzerland.

PMID- 18087772
TI  - Abstracts of the 1st International Conference on Nitric Oxide and Cancer,
      November 26-28, 2007, Paris, France.

PMID- 18087773
TI  - Abstracts of the 22nd Annual Meeting of the North American Spine Society, October
      23-27, 2007, Austin, Texas, USA.

PMID- 18087774
TI  - Northern Uganda: looking for peace.

PMID- 18087775
TI  - The battle to reform health-care coverage in California.

PMID- 18087776
TI  - From 'perfect mix' to 'potion magique'-- regulatory T cells and anti-inflammatory
      cytokines as adjuvant targets.

PMID- 18087777
TI  - Indian biotech's bumpy road.

PMID- 18087780
TI  - Audit response rates.

PMID- 18087781
TI  - A possible solution of brain drain.

PMID- 18087782
TI  - Gas chromatography problem solving and troubleshooting. Are there any problems
      using a low mass ion like this for quantitation?

PMID- 18087783
TI  - The Texas Dental Association official 2007-2008 directory of members.

PMID- 18087784
TI  - [Bone metastases].

PMID- 18087786
TI  - [Physicians with Narrower Limits].

PMID- 18087785
TI  - [Should prevention in Danish general practice be evidence-based or demand
      based?].

PMID- 18087787
TI  - Abstracts of the 60th Annual Scientific Meeting of the Gerontological Society of
      America, November 16-20, 2007, San Francisco, California, USA.

PMID- 18087788
TI  - [Drug industry's "offers" to health personnel].

PMID- 18087789
TI  - [Chronological landmarks].

PMID- 18087790
TI  - [Rupture and overture, words or acts?].

PMID- 18087791
TI  - Exenatide: new drug. Type 2 diabetes for some overweight patients.
AB  - (1) When type 2 diabetes is inadequately controlled with oral antidiabetic
      therapy, one option is to add subcutaneous insulin injections (or to accept less
      stringent glycaemic control). However, since the effects of adding insulin have
      only been evaluated in the short-term, effects on long-term clinical outcomes
      remain unknown. (2) Exenatide, a drug belonging to a new pharmacological class
      (incretin analogues), is marketed as a subcutaneously administered adjunct to
      inadequately effective oral antidiabetic therapy in adults with type 2 diabetes.
      (3) Three placebo-controlled trials lasting 7 months showed that adding exenatide
      to metformin and/or a glucose-lowering sulphonylurea yielded an HbA1c level of 7%
      or less in about 40% of patients treated with exenatide 10 micrograms twice a
      day, versus about 10% of patients on placebo. The potential impact of exenatide
      on morbidity and mortality is not known. (4) In two trials versus insulin
      glargine and in one trial versus insulin aspart (+ isophane insulin), exenatide
      was as effective as the various insulins in controlling HbA1c levels. (5) During
      clinical trials, patients receiving exenatide lost an average of about 2 kg after
      6 months, while insulin was associated with a weight gain of about 2 kg. (6)
      There was a similar incidence of hypoglycaemia with exenatide and insulin. In
      patients treated with exenatide, concomitant use of glucose-lowering
      sulphonylurea increases the risk of hypoglycaemia. (7) More than half of patients
      on exenatide experienced nausea, versus fewer than 10% of patients on insulin
      glargine. (8) The long-term consequences of the presence of antiexenatide
      antibodies on the effectiveness of treatment are not known. (9) Exenatide is
      administered in two subcutaneous injections a day, at fixed doses. Insulin is
      administered in one or several injections a day, at doses adjusted to self
      monitored blood glucose levels. (10) Adding insulin rather than exenatide is a
      better option in general when oral antidiabetic therapy fails in patients with
      type 2 diabetes, as we have more experience with insulin and there is no evidence
      of important advantages with exenatide. The latter should be reserved for
      situations in which weight gain is a major problem.

PMID- 18087792
TI  - [The art of caring, portraits of women and men of progress].

PMID- 18087793
TI  - [Saint John of God (1495-1550)].

PMID- 18087794
TI  - Executive snapshot. Weiss leads Biotest from nature to launch.

PMID- 18087795
TI  - [Epoietins (EPO)].

PMID- 18087796
TI  - Improving glucose management: ten steps to get more patients with type 2 diabetes
      to glycaemic goal. Recommendations from the Global Partnership for Effective
      Diabetes Management.
AB  - Despite increasingly stringent clinical practice guidelines for glycaemic
      control, the implementation of recommendations has been disappointing, with over
      60% of patients not reaching recommended glycaemic goals. As a result, current
      management of glycaemia falls significantly short of accepted treatment goals.
      The Global Partnership for Effective Diabetes Management has identified a number
      of major barriers that can prevent individuals from achieving their glycaemic
      targets. This article proposes 10 key practical recommendations to aid healthcare
      providers in overcoming these barriers and to enable a greater proportion of
      patients to achieve glycaemic goals. These include advice on targeting the
      underlying pathophysiology of type 2 diabetes, treating early and effectively
      with combination therapies, adopting a holistic, multidisciplinary approach and
      improving patient understanding of type 2 diabetes. Implementation of these
      recommendations should reduce the risk of diabetes-related complications, improve
      patient quality of life and impact more effectively on the increasing healthcare
      cost related to diabetes.

PMID- 18087797
TI  - Buprenorphine + naloxone: new combination. Opiate dependence: no proof of reduced
      risk of self-administered injection.
AB  - (1) Two drugs with similar efficacy are available in France for heroin
      replacement therapy: methadone and buprenorphine. (2) Buprenorphine is sold in
      the form of sublingual tablets, but some patients dissolve and inject them.
      Methadone is the main alternative for these patients. Other intravenous opiate
      derivatives can also be tried, although they have not been approved for this
      indication. (3) In order to help prevent patients from injecting themselves with
      buprenorphine, a sublingual combination of buprenorphine + naloxone is to be
      marketed in France. (4) From a pharmacological point of view, this combination
      makes sense. Naloxone, an opiate antagonist, is very poorly absorbed with
      sublingual administration, but if it is injected intravenously, it will
      antagonise the effects of buprenorphine. However, clinical studies are needed to
      determine whether or not this prevents injection. (5) A double-blind trial in 326
      patients compared replacement therapy with buprenorphine 16 mg + naloxone 4
      mg/day versus buprenorphine 16 mg + placebo. The addition of naloxone did not
      reduce the efficacy of sublingual buprenorphine, but the frequency with which
      patients injected the drugs was not studied in this trial. (6) This combination
      of buprenorphine + naloxone has not been directly compared with methadone. (7) In
      addition to the classical adverse effects of opiates, buprenorphine can cause
      hepatic adverse effects. (8) Little evidence is available on the effects of
      intravenous injection of buprenorphine + naloxone. According to an
      epidemiological survey conducted in Finland, where the combination is also
      marketed, about 8% of patients regularly inject it intravenously. (9) Patients
      who are likely to inject buprenorphine should be switched to methadone.

PMID- 18087798
TI  - UNESCO and the study of race relations in Brazil: regional or national issue?

PMID- 18087799
TI  - Demoralised natives, black-coated consumers, and clean spirit: European liquor in
      East Africa, 1890-1955.

PMID- 18087800
TI  - Nebivolol: new indication. Heart failure: 'me-too' available in single dose
      strength only. Select better-assessed betablockers.

PMID- 18087801
TI  - Structural requirements of 2',4',6'-tris(methoxymethoxy) chalcone derivatives for
      anti-inflammatory activity: the importance of a 2'-hydroxy moiety.
AB  - Butein, a natural chalcone, has anti-inflammatory and hepatoprotective activity.
      One synthetic derivative of butein, 2',4',6'-tris(methoxymethoxy)chalcone (TMMC),
      has potent anti-inflammatory activity via an HO-1 (heme oxygenase 1) dependent
      pathway. The alpha,beta-unsaturated ketone moiety in both TMMC and chalcones
      could be important in mediating this effect. To investigate the structural
      requirements of TMMC derivatives for anti-inflammatory effects, we modified the
      alpha,beta-unsaturated ketone moiety through catalytic hydrogenation, hydride
      reduction, or introduction of a triple bond. In addition, we performed structural
      modifications such as converting the -OMOM group to an -OMe or -OH group.
      Generally, modifications in the alpha,beta-unsaturated ketone caused a
      significant decrease or loss of anti-inflammatory activity, which is consistent
      with the role of the alpha,beta-unsaturated ketone group acting as a Michael
      acceptor of nucleophilic species like glutathione or cysteine residues on
      proteins. Chemically, the electron-donating substituents could make the thiol
      adduct more stable by decreasing the acidity of the alpha-hydrogen and slowing
      the speed of the retro-Michael reaction. Also, like previous studies, the 2'
      hydroxy group was crucial in increasing the anti-inflammatory effect. The 2'
      hydroxy group produced potent anti-inflammatory effects by increasing the
      electrophilic properties of alpha,beta-unsaturated ketones due to hydrogen
      bonding between the 2'-hydroxy group and the ketone moiety.

PMID- 18087802
TI  - Neuroprotective coumarins from the root of Angelica gigas: structure-activity
      relationships.
AB  - An n-butanol-soluble fraction of the root of Angelica gigas Nakai (Umbelliferae)
      exhibited significant protection against glutamate-induced toxicity in primary
      cultured rat cortical cells. Using neuroprotective activity-guided fractionation,
      nine coumarins; marmesinin (1), nodakenin (2), columbianetin-O-beta-D
      glucopyranoside (3), (S)-peucedanol-7-O-beta-D-glucopyranoside (4), (S)
      peucedanol-3'-O-beta-D-glucopyranoside (5), skimmin (6), apiosylskimmin (7),
      isoapiosylskimmin (8) and magnolioside (9), were isolated from the n-butanol
      fraction. Of these nine coumarins, three dihydrofuranocoumarins; 1, 2 and 3,
      exhibited significant neuroprotective activities against glutamate-induced
      toxicity, exhibiting cell viabilities of about 50% at concentrations ranging from
      0.1 to 10 microM. To explore the structure-activity relationships of coumarins,
      sixteen previously isolated compounds; 10-25, were simultaneously evaluated in
      the same system. Our results revealed that cyclization of the isoprenyl group,
      such as dihydropyran or dihydrofuran, or the furan ring at the C-6 position of
      coumarin, as well as lipophilicity played an important role in the
      neuroprotective activity of coumarins.

PMID- 18087803
TI  - Antimicrobial phenolic derivatives from Dendranthema zawadskii var. latilobum
      Kitamura (Asteraceae).
AB  - A phytochemical study on the root of Dendranthema zawadskii var. latilobum
      Kitamura, using a series of silica gel column chromatography and reversed phase C
      18 HPLC chromatography, led to the isolation of (1S, 2S)-1, 2, 3-trihydroxy-1-(3,
      4-methylenedioxyphenyl)propane (1), 4-methoxycinnamic acid (2), acacetin (3) and
      caffeic acid methyl ester (4). The structures of these compounds were determined
      using spectroscopic analyses (UV, IR, HRTOFMS and NMR), with comparison of their
      spectral data with previously reported values. Compound 1 was isolated for the
      first time, with compounds 2 and 4 from this plant reported for the first time.
      The antibacterial and antifungal activities of the isolated compounds were
      measured using the disc diffusion method. Also, their cytotoxicities against the
      cancer cell lines, A549, B16F1 and SK-Mel-2, and brine shrimp lethalities were
      evaluated.

PMID- 18087804
TI  - Synthetic and biological studies on natural cyclic heptapeptide: segetalin E.
AB  - Present investigation describes the first total synthesis of a proline-rich
      cyclic peptide segetalin E (8) by solution phase technique. The chemical
      structure of the compound was elucidated by FT-IR, 1H-NMR, 13C-NMR, FAB-MS
      spectral data and elemental analyses. The newly synthesized peptide was subjected
      to pharmacological screening and found to exhibit high cytotoxicity against
      Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines
      with IC50 values of 3.71 and 9.11 microM, in addition to good anthelmintic
      activity against earthworms M. konkanensis and P. corethruses at a dose of 2
      mg/mL.

PMID- 18087805
TI  - Two new triterpene glycosides from the Vietnamese sea cucumber Holothuria scabra.
AB  - Two new triterpene glycosides, namely holothurin A3 (1) and A4 (2) were isolated
      from the methanol extract of the sea cucumber, Holothuria scabra, with their
      structures elucidated from the spectroscopic evidence (1D NMR, 2D NMR, ESI-MS and
      HRESI-MS). Compounds 1 and 2 were found to be strongly cytotoxic to both cancer
      cell lines, KB and Hep-G2, with 50% inhibitory concentrations (IC50) of 0.87 and
      0.32 microg/mL (for compound 1) and of 1.12 and 0.57 microg/mL (for compound 2),
      respectively.

PMID- 18087806
TI  - Antioxidant and antiatherogenic activity of cis-Hinokiresinol from Trapa
      pseudoincisa.
AB  - cis-Hinokiresinol, also known as (+)-nyasol, was isolated for the first time from
      an aquatic herbaceous plant, Trapa pseudoincisa NAKAI, via silica gel and
      octadecyl silica gel column chromatographies. The chemical structure was
      determined via analyses of the spectroscopic data, including NMR, MS and IR. cis
      Hinokiresinol was also found to exhibit antioxidant and antiatherogenic
      activities. The ICso values for the scavenging activities of cis-hinokiresinol on
      ABTS cation and superoxide anion radicals were 45.6 and 40.5 microM,
      respectively. The IC50 values for the inhibitory effects on Lp-PLA2, hACAT1,
      hACAT2 and LDL-oxidation were 284.7, 280.6, 398.9 and 5.6 microM, respectively.

PMID- 18087807
TI  - Biological activities of the chemical constituents of Erythrina stricta and
      Erythrina subumbrans.
AB  - Phytochemical investigation of the hexane and CH2Cl2 extracts of Erythrina
      stricta roots and E. subumbrans stems led to the isolation of six pterocarpans,
      one flavanone, one isoflavone, two alkaloids, five triterpenes, six steroids and
      alkyl trans-ferulates. The structures of all known compounds were determined on
      the basis of spectroscopic evidence. Sophoradiol (15), a mixture of stigmast-4-en
      3-one (19) and stigmasta-4,22-dien-3-one (20), lupeol (21), cycloeucalenol (22),
      a mixture of 3beta-hydroxystigmast-5-en-7-one (23) and 3beta-hydroxystigmast-5,22
      dien-7-one (24) and melilotigenin C (25) were first isolated from the genus
      Erythrina. The isolated compounds were evaluated for antiplasmodial activity,
      antimycobacterial activity and cytotoxicity. Among the tested compounds, 5
      hydroxysophoranone (8) exhibited the highest antiplasmodial activity against
      Plasmodium falciparum (IC50 2.5 microg/mL). Compound 8, erystagallin A (5),
      erycristagallin (7) and erysubin F (10) showed the same level of
      antimycobacterial activity against Mycobacterium tuberculosis (MIC 12.5
      microg/mL). For cytotoxicity, erybraedin A (2) showed the highest activity
      against the NCI-H187 and BC cells (IC50 2.1 and 2.9 microg/mL, respectively),
      whereas 10 exhibited the highest activity against the KB cells (IC50 4.5
      microg/mL).

PMID- 18087808
TI  - Cytotoxic and DNA topoisomerases I and II inhibitory constituents from the roots
      of Aralia cordata.
AB  - Bioactivity-guided fractionation, based on the DNA topoisomerase inhibitory
      activity, lead to the isolation of five compounds (1-5) from the methylene
      chloride extract of the roots of Aralia cordata Thunb. (Araliaceae). These
      compounds were identified as ent-pimara-8(14), 15-dien-19-oic acid (1), ent
      pimara-8(14), 15-dien-18-oic acid (2), 16alpha-hydrogen-17-isovaleryloxy-ent
      kauran-19-oic acid (3), 16alpha-hydroxy-17-isovaleryloxy-ent-kauran-19-oic acid
      (4) and dehydrofalcarindiol-8-acetate (5) from their spectral data. Compound 3
      was isolated for the first time from this plant, and also showed the strongest
      inhibition of both DNA topoisomerase I and II activities, with 53 and 96%
      inhibitions, respectively, at a concentration of 20 microM. However, all the
      compounds exhibited either weak or no cytotoxicities against the human colon
      carcinoma cell line (HT-29), the human breast carcinoma cell line (MCF-7) and
      human hepato blastoma cell line (HepG-2).

PMID- 18087809
TI  - Gene expression profiles during the activation of rat hepatic stellate cells
      evaluated by cDNA microarray.
AB  - Hepatic stellate cells (HSCs) are activated by producing potentially injurious
      connective tissue components during hepatic fibrosis, thereby exerting a pivotal
      action in the development of liver fibrogenesis. The aim of this study was to
      investigate differences in gene expression patterns during the activation of HSCs
      using complementary cDNA microarrays. HSCs were isolated from normal rat livers
      and cultured for 0 (3 h), 3, 5 and 7 d. RNA was extracted from cultured cells at
      each point. The target RNA was hybridized to gene-specific sequence probes
      immobilized on chips. The hybridization signal was assessed using a confocal
      laser scanner. Comparison of hybridization signals and patterns allows the
      identification of mRNAs that are expressed differentially. Statistical analysis
      was used to classify and cluster the genes according to their up- or
      downregulation. As a result, 33 upregulated early-stage and 36 upregulated late
      stage gene candidates were identified. This time-based study revealed a number of
      newly discovered genes involved in fibrogenesis during the activation of HSCs.

PMID- 18087810
TI  - Effect of hydrogen peroxide on VIP-induced relaxation of the cat lower esophageal
      sphincter.
AB  - We investigated the effects of hydrogen peroxide (H2O2) on relaxation of the cat
      lower esophageal sphincter (LES). Vasoactive intestinal peptide (VIP) caused dose
      dependent relaxation of LES, and H2O2 reduced VIP-induced relaxation. Relaxation
      was also attenuated by pertussis toxin (PTX), indicating a Gi/o component. VIP
      treatment increased [35S]GTPgammaS binding to Gs and Gi3 protein, but not to Go,
      Gq, Gil or Gi2. This increase in Gs or Gi3 binding was reduced by H2O2. However,
      the relaxation induced by sodium nitroprusside (SNP), 3-morpholino sydnomine (SIN
      1), 8-br cGMP (cGMP analog), forskolin (adenylate cyclase activator), and
      dibutyryl-cAMP (a stable cAMP analog) was not reduced by H2O2. These data suggest
      that H202 inhibits VIP-induced relaxation via a Gi-dependent pathway, perhaps by
      inhibiting the activation of G(i3) or Gs downstream of the VIP receptor and
      independent of cAMP or NO-cGMP signaling.

PMID- 18087811
TI  - Gastroprotective and antioxidant effects of amiodarone on indomethacin-induced
      gastric ulcers in rats.
AB  - Reactive oxygen species (ROS) have been implicated in the etiology of
      indomethacin-induced gastric mucosal damage. This study investigated amiodarone's
      protective effects against oxidative gastric mucosal damage induced by
      indomethacin. Amiodarone is a widely used antiarrhythmic agent. We have
      investigated alterations in the glutathione level, and the activities of
      antioxidative enzymes [superoxide dismutase, catalase, glutathione s-transferase
      glutathione reductase and myeloperoxidase], as markers for ulceration process
      following oral administration of amiodarone and ranitidine in rats with
      indomethacin-induced ulcers. In the present study we found that 1) amiodarone,
      lansoprazole and ranitidine reduced the development of indomethacin-induced
      gastric damages, at a greater magnitude for amiodarone and lansoprazole than for
      ranitidine; 2) amiodarone and ranitidine alleviated increases in the activities
      of catalase and glutathione s-transferase enzymes resulting from ulcers; 3)
      amiodarone and ranitidine ameliorated depressions in the glutathione level and
      the activities of superoxide dismutase and glutathione reductase enzymes caused
      by indomethacin administration; and 4) all doses of amiodarone amplified the
      myeloperoxidase activity resulting from indomethacin-induced gastric ulcers. The
      results indicate that the gastroprotective activity of amiodarone, which may be
      linked to its intrinsic antioxidant properties, cannot be attributed to its
      effect on myeloperoxidase activity.

PMID- 18087812
TI  - Inhibition of topoisomerase I activity and efflux drug transporters' expression
      by xanthohumol. from hops.
AB  - Xanthohumol (XN) and its related compounds were evaluated for their cytotoxicity
      against four different human cancer cell lines, A549 (lung), SK-OV-3 (ovarian),
      SK-MEL-2 (melanoma), and HCT-15 (colon) using a sulforhodamine B assay. XN showed
      the most active cytotoxicity against the human cancer cell lines. Isoxanthohumol,
      8-prenylnaringenin, and xanthohumol 4'-O-beta-D-glucopyranoside showed comparable
      cytotoxicity and (2S)-5-methoxy-8-prenylnaringenin 7-O-beta-D-glucopyranoside was
      the least cytotoxic compound. The anticancer properties of XN, the most active
      cytotoxic compound, were further investigated. XN showed an inhibitory effect on
      the activity of DNA topoisomerase I (topo I), which was measured from the
      relaxation of supercoiled DNA. The inhibition of topo I by XN might explain the
      cytotoxicity against the human cancer cell lines. Moreover, the expression of the
      drug efflux genes was investigated to predict the drug resistance. XN clearly
      decreased the mRNA levels of ABCB1 (MDR1), ABCC1 (MRP1), ABCC2 (MRP2), and ABCC3
      (MRP3). These results suggest that XN has anticancer properties by inhibiting the
      topo I activity and it might be used in conjunction with other anticancer
      chemotherapeutic agents to reduce the drug resistance inhibiting the efflux drug
      transporters.

PMID- 18087813
TI  - Dendritic cells process antigens encapsulated in a biodegradable polymer,
      poly(D,L-lactide-co-glycolide), via an alternate class I MHC processing pathway.
AB  - Biodegradable nanospheres generated from a biocompatible polymer, poly(D,L
      lactide-co-glycolide) (PLGA), have been studied extensively as implantable
      reservoirs for sustained-release drug delivery. PLGA-nanospheres have also been
      studied as vehicles to deliver antigens to phagocytes. The intracellular
      processing pathway of antigens delivered to phagocytes by PLGA particles was
      studied in the present study. Ovalbumin (OVA) encapsulated with PLGA (OVA
      nanosphere) was efficiently captured, processed and presented on class I major
      histocompatibility complex (MHC-I) by dendritic cells (DCs). The MHC-I processing
      of OVA-nanospheres was resistant to lactacystin, a proteosome inhibitor, and
      brefeldin A, which blocks anterograde transport from the endoplasmic reticulum
      (ER) through the Golgi apparatus. Chloroquine, which inhibits phagolysosomal
      enzymes by increasing phagolysosomal pH, inhibited MHC-I processing of OVA
      nanospheres. In addition, DCs generated from TAP-/- mice were markedly suppressed
      in MHC-I processing of OVA-nanospheres. These results demonstrate that DCs
      process phagocytosed OVA-nanospheres via a vacuolar alternate MHC-I pathway for
      presentation of OVA peptides to T lymphocytes.

PMID- 18087814
TI  - Protection of rabbit kidney from ischemia/reperfusion injury by green tea
      polyphenol pretreatment.
AB  - Reactive oxygen species (ROS) have been implicated in the pathogenesis of renal
      injury after ischemia/reperfusion (I/R). Recently, green tea polyphenols (GTP)
      have been found to protect the myocardium and liver against II/R injury. Less
      attention, however, has been paid to the protective effects of GTP with respect
      to the kidneys. This study was designed to determine whether GTP could protect
      renal cells from ischemic injury. The rabbits were divided into three groups of
      equal size: control (sham-operated), I/R + vehicle (normal saline) and I/R + GTP
      groups. Each group consisted of six rabbits. Animals underwent 30, 60, 90 and 120
      min of ischemia, followed by 24 h of reperfusion, respectively. GTP (200
      microg/kg) or the vehicle was administered 45 min prior to commencement of I/R.
      The results demonstrated that GTP administration resulted in a significant (P <
      0.05) reduction of renal damage after 90 min of ischemia, as indicated by the
      decreased levels of creatinine and urea nitrogen in serum. These results were
      confirmed by histological examinations, which showed that GTP pretreatment
      inhibited necrosis and sloughing of the proximal tubules induced by I/R.
      Examinations also showed decreased necrotic areas in the medulla and decreased
      glomerular collapse in the I/R-injured rabbits. Moreover, the infiltration of
      CD8+ T cells was considerably decreased in GTP-treated kidneys. The results of
      this study suggest that GTP can reduce renal injury by preventing the oxidative
      stress dependent on I/R and may be used in renal transplantation as an
      antioxidant.

PMID- 18087815
TI  - Anti-proliferate and pro-apoptotic effects of 2,3-dihydro-3,5-dihydroxy-6-methyl
      4H-pyranone through inactivation of NF-kappaB in human colon cancer cells.
AB  - Many natural compounds have been shown to prevent cancer cell growth through the
      redox regulation of transcription factors. NF-kappaB, a redox transcription
      factor, has been implicated in the apoptotic cell death of several cancer cells.
      This study examined whether or nor 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyranone
      (DDMP) isolated from onions can modulate the activity of NF-kappaB, thereby
      induce the apoptotic cell death of colon cancer cells. Treatment with different
      DDMP concentrations (0.5-1.5 mg/mL) for various periods (0-48 h) inhibited the
      growth of colon cancer cells (SW620 and HCT116) followed by the induction of
      apoptosis in a dose dependent manner. It was also found that DDMP modulated tumor
      necrosis factor-alpha (TNF-alpha) and tetradeanoyl phorbol acetate (TPA)-induced
      NF-kappaB transcriptional and DNA binding activity. Moreover, DDMP suppressed the
      NF-kappaB target anti-apoptotic genes (Bcl-2), whereas it induced the expression
      of the apoptotic genes (Bax, cleaved caspase-3 and cleaved PARP). These results
      suggest that DDMP from onions inhibit colon cancer cell growth by inducing
      apoptotic cell death through the inhibition of NF-kappaB.

PMID- 18087816
TI  - Inhibition of human ovarian tumor growth by cytokine-induced killer cells.
AB  - Despite the recent improvement in the treatment of ovarian cancer, this disease
      is still leading cause of cancer death in women. In this study, the anti-tumor
      activity of cytokine-induced killer (CIK) cells against human ovarian cancer was
      evaluated in vitro and in vivo. Although CD3+CD56+ cells were rare in fresh human
      peripheral blood mononuclear cells, they could expand more than 1,000-fold on day
      14 in the presence of anti-CD3 antibody plus IL-2. At an effector-target cell
      ratio of 30:1, CIK cells destroyed 45% of SK-OV-3 human ovarian cancer cells,
      which was determined by the 51Cr-release assay. In addition, CIK cells at a dose
      of 23 million cells per mouse inhibited 73% of SK-OV-3 tumor growth in nude mouse
      xenograft assay. This study suggests that CIK cells may be used as an adoptive
      immunotherapy for patients with ovarian cancer.

PMID- 18087817
TI  - Two new phenolic constituents of Humulus japonicus and their cytotoxicity test in
      vitro.
AB  - Two new phenolic constituents (4 and 6), together with four known constituents,
      methyl ferulate (1), eugenyl-beta-D-glucopyranoside (2), apigenin-7-O-beta-D
      glucopyranoside (3), and (E)-resveratrol-3-O-beta-D-glucopyranoside (5) were
      isolated from the MeOH extract of the aerial part sof Humulus japonicus. The
      structures of the new compounds were determined by spectroscopic methods to be
      divarin-3-O-beta-glucopyranoside (4), and lariciresinol-9-O-beta-xylopyranoside
      (6). Compounds 1 and 3 exhibited moderate cytotoxicity against two human cancer
      cell lines (SK-OV-3 and HCT15) with ED50 values ranging from 8.84 to 8.79 microM.

PMID- 18087818
TI  - Downregulation of peritoneal macrophage activity in mice exposed to bisphenol A
      during pregnancy and lactation.
AB  - Bisphenol A (BPA) is an environmental endocrine disrupter that is known to be
      transferred to the fetus via the placenta and to the neonate via milk. In this
      study, we investigated BPA-induced alterations of the activities of murine
      peritoneal macrophages in dams and 7 week old offspring of dams exposed to BPA
      from gestational day 7 until lactation on day 21 after delivery, i.e. 34-36 days.
      BPA was administered in drinking water at three doses, 15, 75, and 300 mg/L. Dams
      were sacrificed 21 days after delivery and offspring at the age of 7 weeks.
      Peritoneal macrophages were cultured in the presence of LPS or LPS plus IFN-gamma
      for 2 or 4 days. We found that nitric oxide (NO) production by maternal
      macrophages was significantly decreased in a BPA-dose dependent manner. However,
      while a significant reduction of NO production by macrophages in the offspring
      was observed at BPA concentrations of 75 mg/L and 300 mg/L in drinking water,
      this effect was not seen at the lowest concentration of 15 mg/L. Similar
      inhibition of tumor necrosis factor-alpha (TNF-alpha) production was observed
      with macrophages from both BPA-exposed dams and offspring. Thus, our results
      suggest that exposure to BPA during gestation and lactation induces
      downregulation of the activities of macrophages in both dams and offspring.

PMID- 18087819
TI  - Effect of probenecid on the biliary excretion of belotecan.
AB  - The purpose of this study was to investigate the effect of probenecid, an
      inhibitor of the MRP2/ ABCC transporter, on the pharmacokinetics and transport of
      belotecan (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin). The effect of
      probenecid on the pharmacokinetics of belotecan was studied in rats. When
      belotecan was injected as a bolus dose of 5 mg/kg after probenecid was infused at
      a rate of 42.8 mg/2 mL/h/kg, the cumulative biliary excretion amounts and biliary
      clearance (CL(b)) of belotecan decreased (28.29 +/- 2.83 versus 19.96 +/- 1.45%
      of dose and 161.01 +/- 26.95 versus 92.66 +/- 1.45 mL/min/kg), whereas the
      systemic pharmacokinetics did not change. This indicates that the MRP2
      transporter is involved in the biliary excretion of belotecan. The involvement of
      MRP2 in the secretory transport was further characterized using Caco-2 cell
      monolayers expressing MRP2. The apparent permeability across Caco-2 cell
      monolayers from basolateral to apical was 2.3 times greater than that from the
      apical to the basolateral side at the 50 microM belotecan. In addition,
      probenecid significantly decreased the basolateral-to-apical transport of
      belotecan (52.9%). These results indicate that MRP2 is involved in the secretory
      transport of belotecan in biliary excretion.

PMID- 18087820
TI  - Gravimetric analysis and differential scanning calorimetric studies on glycerin
      induced skin hydration.
AB  - A thermal gravimetric analysis (TGA) and a differential scanning calorimetry
      (DSC) were carried out to characterize the water property and an alteration of
      lipid phase transition of stratum corneum (SC) by glycerin. In addition, the
      relationship between steady state skin permeation rate and skin hydration in
      various concentrations of glycerin was investigated. Water vapor absorption
      desorption was studied in the hairless mouse stratum corneum. Dry SC samples were
      exposed to different conc. of glycerin (0-50%) followed by exposure to dry air
      and the change in weight property was monitored over time by use of TGA. In DSC
      study, significant decrease in DeltaH of the lipid transition in 10% glycerin and
      water treated sample: the heat of lipid transition of normal, water, 10% glycerin
      treated SC were 6.058, 4.412 and 4.316 mJ/mg, respectively. In 10% glycerin
      treated SCs, the Tc of water shifts around 129 degrees C, corresponding to the
      weakly bound secondary water. In 40% glycerin treated SC, the Tc of water shifts
      to 144 degrees C corresponding to strongly bound primary water. There was a good
      correlation between the hydration property of the skin and the steady state skin
      flux with the correlation coefficient (r2=0.94). As the hydration increased, the
      steady state flux increased. As glycerin concentration increased, hydration
      property decreased. High diffusivity induced by the hydration effect of glycerin
      and water could be the major contributing factor for the enhanced skin permeation
      of nicotinic acid (NA).

PMID- 18087821
TI  - [The need for a fifth faculty of medicine and where to locate it].

PMID- 18087822
TI  - [A fifth faculty of medicine in the Galil].

PMID- 18087823
TI  - [Permanent pacemaker implantation after heart surgery: incidence and
      indications].
AB  - BACKGROUND: New conduction disturbances requiring pacemaker implantation occur in
      about 1-3% of patients undergoing heart surgery. We reviewed our experience with
      patients undergoing heart surgery between the years 1993-2005 in order to
      identify predictors for pacemaker requirement. METHODS: There were 4999 patients
      aged 64 +/- 12 years. Coronary bypass was performed in 3448 (69%), valve surgery
      in 831 (17%), combined procedures in 623 (12%), and other procedures in 97 (2%).
      RESULTS: Overall, 72 (1.4%) patients required pacemaker implantation for the
      following indications: complete atrioventricular block (AVB) in 59, second degree
      AVB in 2, severe bradycardia (< 40 beats/min) in 9, first degree AVB with left
      bundle branch block (LBBB) in 1, and bifascicular block in 1. For patients
      undergoing aortic valve replacement, the incidence of pacemaker implantation was
      5%. Multivariate analysis identified the following predictors for pacemaker
      implantation: LBBB, aortic valve replacement, and elevated CPK-MB levels after
      surgery. CONCLUSIONS: Patients undergoing heart surgery will require a permanent
      pacemaker in about 1.4% of cases. Based upon the recognition of predictors for
      pacemaker requirement, we recommend early implantation in order to enable early
      mobilization and shorter hospital stay.

PMID- 18087824
TI  - [Pleural effusion following coronary bypass surgery].
AB  - BACKGROUND: Pleural effusion is a common finding after coronary artery bypass
      surgery (CABG). We sought to determine the incidence and patient characteristics
      predictive of its appearance, in addition to the effect of post-operative
      treatment with enoxaparin. METHODS: We retrospectively examined 893 patients
      undergoing CABG: 520 consecutive patients did not receive enoxaparin, and 373
      patients received it. All early (up to 10 days) peri-operative chest radiograms
      were examined and graded by the amount of pleural effusion: (i) small-
      obliteration of the costophrenic angle; (ii) moderate-- < 50% of lung field;
      (iii) large-- > 50% of lung field. Patient characteristics as well as operative
      and post-operative parameters were analyzed in order to identify predictors for
      pleural effusion. RESULTS: Pleural effusion was small in 415 patients (46%),
      moderate in 346 (39%) and large in 132 (15%). Older age, female gender and
      congestive heart failure were found to be predictors for pleural effusion by
      multi-variate analysis (p <0.05). Routine use of enoxaparin was not found to be
      associated with pleural effusion after CABG. CONCLUSIONS: Over 50% of patients
      will develop a significant pleural effusion following CABG. Prophylactic
      treatment with enoxaparin does not increase the risk for pleural effusion.

PMID- 18087825
TI  - [Evolution of the surgical repair of thoracoabdominal aortic aneurysm].
AB  - BACKGROUND: Thoracoabdominal aortic aneurysm repair requires complex surgery.
      Clamping of the descending aorta during the operation results in organ
      malperfusion, ischemia, and in some cases, irreversible end-organ damage and
      death. Several methods for organ preservation during the operation evolved,
      resulting in decreased post-operative organ malfunction. Re-attachment of
      intercostal arteries, cerebrospinal fluid drainage, and temporary bypass of the
      clamped aorta and selective perfusion of the spinal cord, intestine, liver and
      kidneys are widely used during the operation. OBJECTIVES: To determine the impact
      of implementation of protective measures on the outcome of thoracoabdominal
      surgery over a decade. METHODS: Between March 1993 and March 2003, 11 patients
      (age 41-80 years, average 60 years) underwent thoracoabdominal aortic aneurysm
      repair in our hospital. Different methods for organ preservation were used during
      the operation. RESULTS: The early survival is 91%. One patient suffered from
      paraplegia and one from mild temporary paraparesis. Two patients died during the
      follow-up period (at 5 months from pneumonia and at 2 years from aortic arch
      rupture). CONCLUSIONS: Implementation of all adjuncts to protect the organs
      dependent on aortic perfusion may eliminate the ischemic consequences of aortic
      clamping.

PMID- 18087826
TI  - [Ventricular assist devices as bridge to heart transplantation in cardiogenic
      shock or terminal heart failure--12 years experience at the Sheba Medical
      Center].
AB  - BACKGROUND: Patients in cardiogenic shock (CS) or with terminal heart failure
      (THF) are at imminent risk of death while waiting for heart transplantation
      (HTx). Implantation of left or bi-ventricular assist device (LVAD/BiVAD) as a
      bridge to HTx may save many of these doomed patients' lives. PATIENTS AND
      METHODS: Between March 1994 and December 2006, 29 terminally ill patients (age
      2.5-65 years, mean 48 years) underwent VADs implantation as bridge to HTx. The
      HeartMate VE LVAD was used in 18 patients, Thoratec pneumatic BiVAD in 7, Berlin
      Heart Excor BiVAD in one, and HeartMate II axial flow, Thoratec pneumatic and
      Biomedicus centrifugal LVADs in one each. Indications for VADs implantation were
      CS in 16 patients (55%) and intractable THF in 13 pts (45%). Etiologies were
      ischemic in 20 patients, idiopathic dilated, myocarditis and congenital in 2
      patients each, and valvular, post partum and HTx graft vasculopathy in one
      patient each. RESULTS: Seventeen patients (59%) survived VADs implantation and
      underwent HTx or are ongoing. Mean survival on VADs was 72 days (range 1-353
      days, total 5.2 patient years). Seven patients (24%) were discharged home while
      on LVAD support for a mean of 146 days. Nine of the transplanted patients (64%)
      were discharged home. In 4 LVAD patients the cause of death was RV failure
      necessitating later implantation of RVAD. CONCLUSIONS: VADs implantation as
      bridge to HTx in CS or THF saves many of these doomed patients, sometimes
      providing quality out-of-hospital life while waiting for HTx. Early recognition
      of RV failure and liberal use of BiVAD is important.

PMID- 18087827
TI  - [Minimally invasive video-assisted mitral valve repair or replacement].
AB  - BACKGROUND: Following the introduction of endoscopic techniques to other surgical
      fields such as general surgery, gynecology urology and thoracic surgery, cardiac
      surgeons sought their own methods of using minimally invasive techniques.
      OBJECTIVES: To examine our operative and mid-term results of mitral valve surgery
      using minimally invasive video-assisted mitral valve surgery. METHODS: From
      January 2000, 130 patients underwent minimally invasive cardiac surgery through
      small right thoracotomy, 72 patients underwent video-assisted mitral valve repair
      or replacement (52 repair and 20 replacement). Patients were selected for the
      procedure according to several inclusion criteria. RESULTS: Intraoperative
      transesophageal echocardiography revealed excellent functional results. There was
      one intraoperative conversion to mid-sternotomy. There were no mortalities and
      only one complication CVA that occurred 24 hours after surgery. CONCLUSIONS:
      Thoracoscopic assisted mitral valve repair (via port access) has the potential to
      provide all the advantages of minimally invasive surgery: accelerates recovery,
      decreases pain, and maintains overall surgical efficacy, while avoiding the
      complications and pathology of midsternotomy. For appropriate patients, this is
      the method of choice in our department.

PMID- 18087828
TI  - [Surgery for ischemic mitral regurgitation: results and long-term follow-up].
AB  - BACKGROUND: The natural history of patients with ischemic mitral regurgitation
      (IMR) shows a poor prognosis. The surgical risk in these patients is high, but
      affords improved survival. We examined long-term results after coronary bypass
      and mitral repair for patients with IMR. METHODS: There were 122 patients
      operated on between the years 1993-2004. Patient age was 65 +/- 10 years, and 89
      (73%) were male. Fifty-one (42%) were in NYHA class IV (mean NYHA class 3.1 +/-
      1); 77 (63%) had pre-operative LV function grade 3-4 (mean LV grade 2.8 +/- 1);
      103 (84%) had MR grade 4 (mean MR grade 3.8 +/- 0.4). All patients received
      mitral valve annuloplasty with a flexible ring (size 26 +/- 1 mm). Number of
      bypass grafts performed was 2.5 +/- 0.9. RESULTS: Operative mortality was 7% (9
      patients). Operative survivors (n = 113) were followed for a mean interval of 34
      months (range 2-91). NYHA class was 2.2 +/- 1. In 65 patients (58%) LV function
      was grade 1-2. Mean MR was 1.6 +/- 1 for the whole group, and 28 (25%) remained
      with MR grade 3-4. Late mortality was 18% (21 patients) 33 +/- 20 months after
      surgery (range 2-62). Predictors for late mortality were poor LV function, NYHA
      class IV, and age > 70 years (p < 0.0001). Overall, residual MR did not emerge as
      a predictor for late mortality. CONCLUSIONS: Surgery for patients with IMR can be
      performed with an acceptable risk. In our patient group, LV function is the major
      determinant for late survival, overshadowing the effect of residual MR.

PMID- 18087829
TI  - [Bipolar radiofrequency and cryoablation for surgical treatment of atrial
      fibrillation].
AB  - BACKGROUND: The widespread use of new sources of energy for ablation of atrial
      fibrillation (AF) raised concerns regarding the safety and efficacy of the
      various devices. This article describes the results of our technique using a
      combination of bipolar radiofrequency (RF) and cryoablation. METHODS: From
      February 2004 till July 2006 this method was used on 94 patients. Fifty patients
      had persistent atrial fibrillation (53%), thirty-one suffered from permanent AF
      (33%) and thirteen patients had paroxysmal AF (14%). Lesions set similar to Maze
      III procedure were used with the addition of right atrial isthmus lesion in the
      area of coronary sinus and without right atrial appendage amputation and septal
      lesion. RESULTS: There were no procedure-related complications and no death or
      major morbidity in general. Average time for ablation procedure was 30 minutes
      (range 27-36 minutes) for biatrial and 16 minutes (range 15-19) for left atrial
      procedures. Seventy-one patients (75%) were discharged in sinus rhythm. At the
      end of the follow-up, seventy-five patients (80%) were in sinus rhythm. Mean
      follow-up was 21 months (1-32 months). Predictor for recurrent AF or atrial
      flutter after procedure was preoperative permanent AF for more than 10 years (p =
      0.037) and cardiac surgery in the past (p = 0.012). CONCLUSION: The use of
      bipolar RF device with cryoprobe is an appealing combination. It enables the
      completion of a Maze III lesion set in an easy, safe and efficient way.

PMID- 18087830
TI  - [Aortic valve sparing surgery].
AB  - BACKGROUND: Over the past 20 years, a series of procedures have been designed to
      reconstruct the aortic root of patients with aortic insufficiency, in whom the
      pathology and hence, the surgery, spares the valve leaflets. The objective of
      this current study was to evaluate our midterm results comparing the
      reimplantation technique with the remodeling technique in patients with aortic
      regurgitation due to aortic dissection, aortic root and ascending aortic
      aneurysms. PATIENTS AND METHODS: During the years 1993 and 2006 we operated on
      209 patients with aortic regurgitation secondary to dilatation of the aortic root
      or ascending aorta with or without aortic dissection. Mean age was 59 years
      (range 21-81 years), 69% of the patients were males; 91 patients had chronic
      aneurysm, while 118 patients presented with acute dissection. Thirty-nine
      patients had Marfan syndrome or it's form fruste. Post-operative follow-up (FU)
      was 82% complete (172 patients) with mean follow-up time of 66 months, and
      completion of FU was continued. RESULTS: Thirty-nine patients underwent the
      reimplantation technique, 89 patients underwent the remodeling technique. Twenty
      five patients underwent only replacement of the ascending aorta on the level of
      the STJ, 11 patients had replacement of the ascending aorta and one sinus. In 45
      of the cases bio-glue was used in addition to replacing the ascending aorta.
      Overall, 30 days mortality was 5.7% (12 patients out of 209). There was no
      difference in mortality rates among the groups of patients who underwent
      reimplantation (chronic aneurysm vs Acute dissection), but significantly higher
      mortality rate was observed among patients who had aortic dissection and
      underwent the remodeling technique compared to the same group of patients who
      underwent reimplantation (6.7% vs 1.1%, P < 0.025). It was also found that Marfan
      patients who had aortic dissection had significantly higher mortality rate when
      undergoing the remodeling technique (7.6% Vs 0%, p < 0.01). Recurrence of AI more
      than 2+ occurred in 11 patients, ten from the remodeling and one from the
      reimplantation group (P = 0.17). Among Marfan patients, recurrence of AI more
      than 2+ occurred in two patients, both underwent remodeling and both had
      dissection of the ascending aorta involving the sinuses of Valsalva. Reoperation
      due to Severe AI was needed for 8 patients, all from the remodeling group and all
      were non-Marfans. CONCLUSIONS: In acute dissection reimplantation provides better
      haemostasis and there may be more stable repair, both in Marfan and non-Marfan
      patients. In Marfans it seems that the reimplantation technique provides better
      long-term results.

PMID- 18087831
TI  - [Cardiac surgery: within the revolution!].
AB  - Cardiac surgery is undergoing major changes. Until recently, coronary artery
      bypass grafting (CABG) constituted the majority of cardiac surgery cases that
      were performed. The sharp rise in percutaneous coronary interventions (PCI)
      mainly due to the development of drug eluting stents resulted in a drop in the
      worldwide number of CABG cases. The cardiac surgery community reacted by
      developing several new surgical procedures and techniques to better treat cardiac
      patients. Some of those procedures are demonstrated in this special issue of the
      Harefuah journal. Those procedures include better techniques to repair the aortic
      and mitral valves, minimally invasive techniques including video assisted
      methodology for valves and CABG surgery, surgery for congestive heart failure
      including new axial flow assist devices, surgery for the treatment of atrial
      fibrillation and more. The excellent results in cardiac surgery caused older and
      sicker patients to be referred to surgery. All these are creating a "revolution"
      in cardiac surgery. Those new technologies, surgical techniques and high risk
      patients require special financing. In order to complete the revolution and
      continue providing advanced "state of the art" cardiac surgery procedures for the
      patients, there is a need for special long term economic planning by the
      government and the Ministry of Health.

PMID- 18087832
TI  - [Shared residency training in internal medicine--a need for the 21st century].
AB  - The crisis that has enveloped internal medicine over the past decade has resulted
      in difficulties in attracting the best and brightest graduates to this
      specialization. Since an increasing number of graduates are female, there is
      often a conflict between raising a family and completing demanding postgraduate
      medical training. We suggest that serious consideration be given to part-time
      training in internal medicine in Israel. This article outlines our proposal and
      reports experience in other countries that supports the concept of postgraduate
      training in a part-time position. We suggest that this idea is suited to internal
      medicine and should be seriously considered by the regulatory authorities.

PMID- 18087833
TI  - [Oocytes in-vitro maturation--a new technique for reproductive endocrinologist
      practitioners].
AB  - In vitro maturation is a new and promising technique in the field of artificial
      reproductive technology. This method provides an alternative treatment to the
      known treatments and a solution for one of the most common and disturbing
      problems of infertility treatment, the hyperstimulation syndrome. The method is
      particularly useful in cases of patients with polycystic ovarian syndrome. The
      physiological process of oocyte maturation requires maturation of the nucleus and
      maturation of the oocyte cytoplasm. In the process of in vitro maturation of the
      oocyte, oocytes in their late stages of maturation are aspirated from the
      follicles and transferred to specific culture conditions to achieve complete
      maturation. The process of oocyte retrieval from small and undeveloped follicles
      needs proper equipment and experience. Therefore, this process requires deep
      understanding of the physiological process of oocyte and follicles growth and
      maturation, proper equipment and especially good experienced laboratory support.
      This review aims to describe the physiological basis for the process, the
      recommended protocols and to report the experience published so far on success
      rates and treatment safety, both maternal and fetal.

PMID- 18087834
TI  - [Update in aortic valve diseases].
AB  - Aortic valve disease is currently the commonest valve disease. The prevalence of
      aortic stenosis reaches 2% to 5% of very elderly patients. It is the second
      commonest indication for cardiac surgery, and the commonest indication for valve
      surgery today. In the European survey, aortic valve disease constituted 60% of
      all valve diseases. There are two important reasons for this finding; 1) 1-2% of
      the population is born with bicuspid aortic valve; 2) the ageing population is
      growing to the stage where significant degenerative aortic valve disease is
      developing. Although the disease is associated with substantial clinical
      consequences, there is currently no effective therapy for the disease other than
      surgical aortic valve replacement. This review focuses on innovations in the
      pathophysiology, diagnosis and treatment of aortic valve diseases (stenosis and
      regurgitation) with special emphasis on the new ACC/AHA 2006 guidelines for the
      management of patients with valvular heart disease. A comparison with the older
      ACC/AHA guidelines and the European guidelines is also presented.

PMID- 18087835
TI  - [An update on diabetic retinopathy].
AB  - Diabetic retinopathy is the most common microvascular complication of diabetes
      mellitus. Research performed over the last several decades has demonstrated the
      benefit of systemic control and ocular treatments in reducing the risk of
      blindness. In the Western world, however, diabetic retinopathy remains the major
      cause of blindness in the working age population and its economical impact is the
      highest among the different ocular diseases. This review discusses the various
      aspects of diabetic retinopathy and includes an update on new research in the
      field.

PMID- 18087836
TI  - [The surgical treatment of diabetic foot complications].
AB  - Neuropathic foot ulcers are the leading cause of hospitalization and major limb
      amputations among diabetic patients. The role of surgery is recognized as an
      important adjunct in their treatment and prevention. Surgical procedures for non
      infected ulcers are indicated when conservative treatment fails and include
      surgical off-loading and wound closure procedures. Surgical procedures for
      infected ulcers are often urgent, including drainage, debridement, partial foot
      and major limb amputations. Preventive reconstructive surgery is indicated when
      conservative treatment fails. These reconstructive procedures are aimed to
      decrease pressure over the areas at risk and to achieve a stable plantigrade foot
      that can be successfully managed with custom shoes and/or braces.

PMID- 18087837
TI  - [Complex posttraumatic stress disorder].
AB  - The characteristic symptoms resulting from exposure to an extreme trauma include
      three clusters of symptoms: persistent experience of the traumatic event,
      persistent avoidance of stimuli associated with the trauma and persistent
      symptoms of increased arousal. Beyond the accepted clusters of symptoms for
      posttraumatic stress disorder exists a formation of symptoms related to exposure
      to extreme or prolonged stress e.g. childhood abuse, physical violence, rape, and
      confinement within a concentration camp. With accumulated evidence of the
      existence of these symptoms began a trail to classify a more complex syndrome,
      which included, but was not confined to the symptoms of posttraumatic stress
      disorder. This review addresses several subjects for study in complex
      posttraumatic stress disorder, which is a complicated and controversial topic.
      Firstly, the concept of complex posttraumatic stress disorder is presented.
      Secondly, the professional literature relevant to this disturbance is reviewed
      and finally, the authors present the polemic being conducted between the
      researchers of posttraumatic disturbances regarding validity, reliability and the
      need for separate diagnosis for these symptoms.

PMID- 18087838
TI  - [Long-term health consequences of polycystic ovaries syndrome: metabolic,
      cardiovascular and oncological aspects].
AB  - The polycystic ovary syndrome (PCOS), then called the Stein-Leventhal syndrome,
      was first described in 1935. Originally, diagnosis required pathognomonic ovarian
      findings and the clinical triad of hirsutism, amenorrhea, and obesity. During
      fertility years, women with PCOS are often seen for immediate concerns such as
      infertility, menstrual irregularity, and symptoms of androgen excess. During the
      past two decades, however, such patients have been observed to have increased
      risk of cardiovascular disease, dyslipidaemia, hypertension and diabetes and
      increased risk for endometrial cancer. The management of polycystic ovary
      syndrome is now complex and includes life style modifications, dietary-induced
      weight loss, oral contraceptives, clomiphene citrate, gonadotropins,
      antiandrogens and insulin-sensitising agents. These observations have led to a
      unique clinical perspective about PCOS--one that recognizes the need to address
      the immediate issues of irregular bleeding, hirsutism, and infertility, but also
      emphasizes the long-term goals of preventing diabetes, heart disease, and cancer.

PMID- 18087839
TI  - [Criteria for the acceptable heart donor: maximizing the use of hearts recovered
      from potential donors in Israel].
AB  - The shortage of available donor hearts limits the number of cardiac
      transplantations worldwide and in Israel as well. This organ shortage results in
      15%-20% annual mortality of heart transplant candidates. For the sub-group of
      hospitalized decompensated heart failure patients depending on continuous
      inotropic support (Status I), the annual mortality is over 50%. Suboptimal
      utilization of donor hearts has been one of the reasons for the organ shortage.
      In 2004, only 42% of the potential donor hearts in Israel were eventually
      transplanted. The objective of this report is to define guidelines regarding the
      suitability of potential cardiac donors allowing more liberal criteria for
      accepting borderline donor hearts. Implementing the new guidelines will permit
      the utilization of organs that otherwise would have been discarded.

PMID- 18087840
TI  - [Stroke as a manifestation of acute Bartonella henselae endocarditis].
AB  - BACKGROUND: Bartonella, a small gram-negative bacillus, causes a variety of
      diseases and presents with different clinical manifestations, one of which is
      infective endocarditis (IE). IE due to B. henselae is associated with a high risk
      of morbidity and mortality due to the destructive potential of the organism to
      the heart valves and due to the great risk of embolic complications. CASE
      DESCRIPTION: A 37-year-old male was admitted to our hospital due to sub-febrile
      fever and weakness. Investigation revealed he had IE caused by B. henselae. His
      mitral valve was severely damaged and he experienced a cerebrovascular event,
      caused by septic emboli. The severe damage to the mitral valve and the presence
      of septic emboli necessitated valvular replacement surgery. The case involved a
      therapeutic dilemma, due to the patient's neurological complications.
      CONCLUSIONS: Since B. henselae is an important pathogen associated with culture
      negative IE, there should be a high index of suspicion for the presence of this
      pathogen in cases presenting with signs of infection associated with embolic
      events. This condition requires a careful diagnostic and therapeutic approach.

PMID- 18087841
TI  - Postoperative cognitive decline, dementia and anaesthesia.

PMID- 18087842
TI  - Health and health care in south Asian communities in the UK.

PMID- 18087843
TI  - Management of recurrent colorectal cancer with positron emission tomography.
AB  - The use of positron emission tomography, on its own and in combination with
      computed tomography, has been integrated into the management algorithm of
      patients with suspected recurrence of colorectal cancer. This article looks at
      the biological basis of positron emission tomography, its clinical advantages and
      disadvantages.

PMID- 18087844
TI  - Screening women at moderate risk of breast cancer.

PMID- 18087845
TI  - Characteristics, diagnosis and treatment of bone and soft tissue sarcomas.

PMID- 18087846
TI  - Buprenorphine in the treatment of opioid dependence.
AB  - Methadone has been the mainstay of pharmacological management of opioid
      dependence since the 1960s but buprenorphine is fast gaining acceptance among
      addiction specialists and patients. This article provides an overview of
      buprenorphine, its pharmacology, clinical efficacy and role in the treatment of
      opioid dependence.

PMID- 18087847
TI  - Dipeptidyl peptidase-iV inhibitors: fixing type 2 diabetes?
AB  - The optimal treatment of type 2 diabetes is currently uncertain. This article
      reviews a new class of oral hypoglycaemic agents: dipeptidyl peptidase-IV
      inhibitors. By potentiating the action of incretins they offer a more
      'physiological' control of blood sugar with fewer side effects, and the
      possibility of ameliorating the decline in beta cell function.

PMID- 18087848
TI  - How to insert a temporary pacing wire.

PMID- 18087849
TI  - Management of foreign bodies in the ears and upper aerodigestive tract.

PMID- 18087850
TI  - Teaching styles: a guide for the foundation year doctor.

PMID- 18087851
TI  - Ultrasound imaging of the carotid arteries.

PMID- 18087852
TI  - Breast abscess.

PMID- 18087853
TI  - Assessment of clinical severity in Dupuytren's disease.
AB  - Every clinician should be aware of the key features in the history and
      examination of the patient with Dupuytren's disease to know when surgical
      referral is appropriate and to inform the patient about causation and prognosis.
      This article outlines the most relevant questions to ask and provides a
      systematic approach to the clinical examination.

PMID- 18087854
TI  - Maternal request caesarean section: maternal vs medical autonomy.

PMID- 18087855
TI  - A practical guide to building a national curriculum.
AB  - The clinical specialities are under-represented in local and national
      undergraduate curricula that are too generic to guide student learning
      adequately. This article gives practical advice, grounded in the published
      literature, on how to develop a speciality-specific national curriculum.

PMID- 18087856
TI  - Lung abscess rather than pneumatocele following kerosene ingestion.

PMID- 18087857
TI  - Giant coronary artery aneurysms and myocardial infarction: aetiology and
      management.

PMID- 18087858
TI  - A snake bite.

PMID- 18087859
TI  - Coronary angiography in chronic aortic dissection.

PMID- 18087860
TI  - Massive inguinoscrotal hernia.

PMID- 18087861
TI  - Paracentesis in the management of ascites.

PMID- 18087862
TI  - Admiral Nelson's amputation.

PMID- 18087863
TI  - Traditional rapid sequence induction for caesarean section is outdated.

PMID- 18087865
TI  - Population living in the Red Sea State of Sudan may need urgent intervention to
      correct the excess dietary iodine intake.
AB  - BACKGROUND: Both inadequate and high intakes of iodine are associated with
      thyroid disease and associated abnormalities. Consumption of foods deficient in
      iodine induces hypothyroidism. Conversely, excessive intake of the nutrient
      precipitates hyperthyroidism. Iodine deficiency causes impairment of thyroid
      hormonogenesis resulting in goiter (struma), cretinism which is associated with
      increased prenatal and infant mortality, deafness, motor disabilities and mental
      retardation due to damage during fetal and neonatal brain development. We have
      assessed the iodine status of school children from the locality of Port Sudan,
      Red Sea State of Eastern Sudan. The primary sources of iodine of the children are
      mainly iodized salt and rations supplied by local donors and various aid agencies
      operating in the Sudan. METHODS: Male and female children (n=141), aged 6 to 12
      years (median age 9.8 years), were selected for the survey using a multistage
      random sampling technique, between May 22 and August 25, 2006. All the children
      were assessed for urinary iodine and visible goiter. In addition, the iodine
      content of twenty salt samples was determined using the lodometric titration
      method and spot test kits. The components of other foods that are routinely
      consumed by the children and households were noted using a questionnaire form.
      FINDINGS: Urinary iodine concentration exceeded 300 microg/l and 1000 microg/l in
      65% and 9.9% of the children, respectively. The highest urinary iodine level was
      1470 microg/l. The prevalence of visible goiter was 17%. All the salt samples
      collected from the schools had more than 150mg potassium iodate per kg of salt.
      CONCLUSIONS: The results of this pilot survey reveal that excessive intake of
      iodine in children exists in Port Sudan. Inappropriate and unregulated local
      fortification of salt and lack of monitoring of the imported and donated salt is
      the primary reason for the excessive intake. There is an urgent need for a
      regulatory mechanism during the process of iodine fortification and at the point
      of entry of imported and donated iodized salt as well as the mode of delivery in
      order to avoid hyperthyroidism and associated disorders. In addition, independent
      professionals should critically evaluate the health impact of excessive
      consumption of the nutrient.

PMID- 18087864
TI  - Fatty acid composition of milk of refugee Karen and urban Korean mothers. Is the
      level of DHA in breast milk of Western women compromised by high intake of
      saturated fat and linoleic acid?
AB  - BACKGROUND: Lower proportions of docosahexaenoic acid (DHA) and total n-3
      metabolites have been reported in breast milk of European, Australian and North
      American women compared with milk of mothers from non-Western countries. This
      difference is not always explained by intakes of marine products. OBJECTIVE: We
      investigated the possibility that the relative composition of DHA and total n-3
      metabolites in breast milk of non-Western mothers with low fat intakes is higher
      than the levels commonly reported in their Western counterparts. SUBJECTS: Mature
      milk of refugee Karen women from two different camps in Thailand (n=26 and n=53),
      and transition milk from urban Korean mothers (n=12) in Seoul was collected. In
      common with their respective community, the mothers have low fat intake, which is
      predominately of plant origin. RESULTS: The percentage levels of DHA and n-3
      metabolites in the milk of the Karen mothers were 0.52 +/- 0.14 and 0.85 +/- 0.24
      (camp 1) and 0.54 +/- 0.22 and 0.92 +/- 0.42 (camp 2). In the Korean milk, DHA
      was 0.96 +/- 0.21 and total n-3 metabolites 1.51 +/- 0.3. CONCLUSION: We
      postulate that the levels of DHA and total n-3 metabolites may be compromised in
      breast milk of mothers on the Western high fat diet. This calls into question the
      use of DHA composition of such milk as a reference for the formulation of milk
      designed, for infant feed or, to test the function of DHA in neuro-visual
      development.

PMID- 18087866
TI  - Action options on omega-3--recommendations, sources, policies.

PMID- 18087867
TI  - Biochemical changes in micro-fungi fermented cassava flour produced from low- and
      medium-cyanide variety of cassava tubers.
AB  - Comparative studies were carried out on the ability of pure strain of Rhizopus
      oryzae and Saccharomyces cerevisae to alter the nutritional quality of cassava
      flour produced from low- and medium-cyanide variety of cassava tuber. Low- and
      medium-cyanide variety of cassava tubers were collected from International
      Institute of Tropical Agriculture (IITA), Ibadan, Nigeria. These tubers were
      washed, peeled, grated and aseptically inoculated with pure strains of Rhizopus
      oryzae and Saccharomyce cerevisae in nutrient solution respectively, before
      allowing them to ferment aerobically for 3 days. The fermented mash was
      subsequently dried and milled into cassava flour. Subsequently, the proximate,
      mineral and the antinutrinet composition of the cassava flour were determined.
      The results of the study revealed that the unfermented flour from low-cyanide
      cassava variety had higher protein, fibre, ash, fat, Ca, Na and K; while those
      produced from medium-cyanide variety, had higher antinutrinet (tannin, cyanide &
      phytate), Zn, Mg and Fe content. However, solid substrate fermentation of the
      cassava mash using Rhizopus oryzae and Saccharomyces cerevisae respectively
      caused a significant (P < 0.05) increase in the protein and fat content. The
      nutrient enrichment was significantly higher (P < 0.05) in flour produced from
      low-cyanide cassava variety. In addition, Saccharomyces cerevisae fermentation
      brought about a higher increase in the nutrient content than Rhizopus oryzae
      fermentation. Conversely, fermentation of the cassava caused a significant
      decrease (P < 0.05) in the antinutrient content of the flour; although, the level
      of decrease was more in the flour produced from low-cyanide variety than medium
      cyanide variety. Nevertheless, there was no significant difference (P > 0.05) in
      the ability of the fungi to decrease the antinutrient (except phytate) of the
      cassava flour. Furthermore, micro-fungi fermentation did not cause a significant
      change (P > 0.05) in mineral content (except Mg and K) of the fermented cassava
      flour. In conclusion, unfermented cassava flour produced from low-cyanide cassava
      tubers had high nutrient composition and low antinutrient content and more
      susceptible to micro-fungi nutrient enrichment and detoxification than medium
      cyanide variety. Furthermore, Saccharomyces cerevisae was more efficient in the
      nutrient enrichment of the cassava flour than Rhizopus oryzae.

PMID- 18087868
TI  - Coagulants modulate the antioxidant properties & hypocholesterolemic effect of
      tofu (curdled soymilk).
AB  - The recent increase in Soymilk and tofu (coagulated soymilk) consumption
      especially in Western Country is due to the recognition of the health benefits of
      soy foods; consumption of soybean would prevent heart diseases. In Nigeria
      Calcium salt, alum and steep water from pap production are usually used as
      coagulant in tofu production. The effect of those coagulants on the antioxidant
      properties of tofu and serum cholesterol, high-density lipoproteins (HDL) and low
      density lipoproteins (LDL) level of albino rats fed tofu for 14 days is been
      assessed. The result of the study revealed that there was no significant
      difference (P > 0.05) in the tofu yield (17.6-18.3%), however steep water
      coagulated tofu had a significantly higher (P < 0.05) total phenol (12.0 g/kg)
      content, reducing power (0.6 OD700) and DPPH free radical scavenging ability
      (69.1%) than tofu produced using other coagulants. Furthermore, feeding albino
      rats with tofu and water ad libitum for 14 days caused a significant decrease (P
      < 0.05) in the serum cholesterol and low-density lipoproteins when compared with
      the control, while there was no significant difference (P > 0.05) in the average
      daily feed intake of the rats. Conversely, there was a significant increase (P <
      0.05) in the serum high-density lipoproteins when compared with the control.
      However, rats fed steep water coagulated tofu had the lowest serum level of
      cholesterol and LDL level followed by those fed CaCl2 and alum coagulated tofu
      respectively, while those fed with calcium chloride coagulated tofu had the
      highest serum HDL level, and closely followed by those fed steep water coagulated
      tofu. It was therefore concluded that of all the coagulant, steep water appeared
      to be the most promising coagulant with regard to the production of tofu with
      higher antioxidant and hypocholesterolemic effect.

PMID- 18087869
TI  - Chemical profile and amino acids composition of edible mushrooms Pleurotus sajor
      caju.
AB  - Two varieties of Pleurotus sajor-caju, obtained from the wild and cultivated (on
      shredded corncobs) were separated into cap and stalk and analysed on dry weight
      basis. The proximate composition (g/100 g) showed that both varieties were highly
      concentrated in crude protein. The cultivated cap (Cc) was found to accumulate
      higher concentration of crude protein (26.34%) and ash (10.37%) than the wild cap
      (Wc), which had higher crude fat (3.90%) and crude fibre (16.32%) concentrations
      while the wild stalk (Ws) contained the highest concentration of crude fibre
      (26.14%). Amino acid analysis showed the mushroom protein to be a rich source of
      nutritionally useful essential amino acids with leucine as the most abundant
      occurring in highest concentration (mg/g) in the Cc (64.8 +/- 0.24). Methionine
      and cysteine concentrations were low as confirmed by their chemical scores (0.29
      0.59). There was a significant difference (P<0.05) in the distribution of amino
      acids in the mushroom varieties and parts. The total essential amino acid (TEAA)
      in the cultivated range between 42.91-43.69% while in the wild it was between
      42.90-43.73 % of the total amino acid content. The amino acid concentration was a
      function of mushroom variety and part selected.

PMID- 18087870
TI  - Prevalence of overweight and obesity in Nigerian preschool children.
AB  - The problem of obesity is taking a worldwide dimension. However, there is paucity
      of data on obesity in Nigerian children. This study was therefore conducted to
      determine the prevalence and factors associated with overweight and obesity among
      Nigerian preschool children. A total of 270 children were recruited from 216
      households using multistage cluster sampling technique. The prevalence of
      overweight and obesity were 13.7% and 5.2% respectively while the prevalence of
      underweight was 8.5%. Although, there was no statistically significant
      relationship between exclusive breastfeeding for 6 months, duration of
      breastfeeding and the prevalence of overweight (P = 0.569, 0.669 respectively),
      the prevalence of overweight decreases with increase in the duration of
      breastfeeding. Ninety-nine (36.3%) children were given infant formula feeds with
      92 (93.9%) children introduced to infant formula feeds before the age of 6
      months. The use of infant formula feeds was significantly associated with
      reduction in the prevalence of overweight (P = 0.041). No linear relationship was
      detected in the association between overweight and socioeconomic class. The
      population shows heterogeneity in their nutritional problem by having mixture of
      obesity and underweight. There is need for trend of obesity to be monitored so
      that timely intervention will be taken and associated morbidity and mortality
      from obesity prevented.

PMID- 18087871
TI  - The malnutrition myth: age isn't everything.

PMID- 18087872
TI  - Keeping the peace.
AB  - By 2008, all front line NHS staff should have received conflict resolution
      training. One trust, an early pioneer, has seen positive results.

PMID- 18087873
TI  - Higher connection.
AB  - Spirituality in health care recent Department of Health policy documents. Nurses
      will need to adapt to an ongoing spiritual evolution in practice.

PMID- 18087874
TI  - Life sentence.
AB  - Seven years ago nurse Dee Winzar was given a life sentence for murdering her
      husband Nic McCarthy. But a growing body of opinion says the verdict was unsafe.

PMID- 18087875
TI  - Back in control.

PMID- 18087876
TI  - The effects of undernutrition in hospitalised patients.
AB  - The prevalence of undernutrition in hospitals is significant, affecting between
      13% and 78% of acute care patients depending on the population studied. This
      article considers the causes and effects of undernutrition and identifies
      strategies to overcome it.

PMID- 18087877
TI  - Educational interventions for patients receiving psychotropic medication.
AB  - This information on best practice is based on a systematic review of research
      published by Blackwell Publishing Asia and conducted by the New South Wales
      Centre for Evidence Based Healthcare. The primary references included in the
      systematic review are available online at: www.blackwell-synergy.com and to
      members of the Institute via the website: www.joannabriggs.edu.au The information
      sheet discusses the following: Knowledge retention. Concordance with therapy.
      Incidence of relapse. Insight. Implications for practice. Recommendations.

PMID- 18087878
TI  - Procedure for pregnancy testing.
AB  - This article summarises the procedure for assessing and undertaking a test to
      determine if a woman is pregnant.

PMID- 18087879
TI  - Providing psychological support for patients with cancer.
AB  - This article focuses on the communication skills required to provide
      psychological support to cancer patients. The article explores factors that
      reduce the effectiveness of communication skills in the practice environment and
      indicates how nurses can improve their ability to be supportive.

PMID- 18087880
TI  - Clostridium difficile.

PMID- 18087881
TI  - Rules of engagement.

PMID- 18087883
TI  - Making the most of retirement.

PMID- 18087882
TI  - Enterprising moves.

PMID- 18087884
TI  - Are nurses and patients still at risk?

PMID- 18087885
TI  - 'We must be reassured that patients' records will be protected appropriately'.

PMID- 18087886
TI  - What's happened to pain management?

PMID- 18087887
TI  - Improving response to signs of patient deterioration.

PMID- 18087888
TI  - The sense of smell.

PMID- 18087889
TI  - Supporting failing students in practice 2: management.
AB  - This two-part unit examines the issue of students who fail in clinical practice.
      Part 1 explored reasons for failure, assessment and emotional challenges mentors
      may face when supporting underperforming students. This part, part 2, discusses
      the management of failing students.

PMID- 18087890
TI  - Health research agenda for East Africa in the new millennium: looking ahead.
AB  - The Regional East African Health Research agenda was presented as a keynote
      speech during the first East African Health and Scientific Conference, held in
      Kampala, Uganda from 28th to 30th March 2007. The agenda was developed through a
      critical analysis of the global, African and Regional East African health
      challenges and mitigating strategies, taking into account the Millennium
      Development Goals (MDG), the Abuja declaration and the New Partnership for
      African Development as background environment, within which the agenda will
      operate. It is proposed to establish a joint mechanism for research coordination,
      promotion and regulation; establish stronger collaborative mechanisms for
      research and training; create a joint Regional East African Community health
      research and development fund; create joint intellectual property rights
      protection mechanism; enhance patenting and link research to industry; create a
      mechanism to enhance translation of research to policy and practice; strengthen
      clinical research capacities; and strengthen innovation and discovery research
      capacities. Effective implementation of this agenda will greatly raise the
      profile and quality of research in the region and improve the health status of
      the East African populations.

PMID- 18087891
TI  - Health research ethics review and needs of institutional ethics committees in
      Tanzania.
AB  - This study was undertaken to describe the performance of health research ethics
      review procedures of six research centres in Tanzania. Data collection was done
      through a self-administered questionnaire and personal interviews. The results
      showed that there were on average 11 members (range = 8-14) in each Research
      Ethic Committee. However, female representation in the committees was low
      (15.2%). The largest proportion of the committee members was biomedical
      scientists (51.5%). Others included medical doctors (19.7%), social scientists
      (7.6%), laboratory technologists (10.6%), religious leaders (4.5%), statisticians
      (3.0%), teachers (1.5%) and lawyers (1.5). Committee members had different
      capacities to carry out review of research proposals (no capacity = 2%; limited
      capacity = 15%; moderate capacity = 20%; good capacity = 48%, excellent capacity
      = 13%). Only half of the respondents had prior ethics review training. Although
      the majority deemed that ethical guidelines were very important (66%), there were
      challenges in the use of ethical guidelines which included lack of awareness on
      the national accreditation mechanisms for ethics committee (59%). Adherence to
      ethical principles and regulations was influenced by being a scientist (OR =
      42.47), being an employee of a professional organization (OR = 15.25), and having
      an interests in the use of ethical guidelines (OR = 10.85) These findings
      indicate the need for capacity strengthening (through training and resource
      support), inclusion of more female representation and other mandatory professions
      to the research ethics committees.

PMID- 18087892
TI  - Prevalence of sexual intercourse among school-going adolescents in Coast
      Province, Kenya.
AB  - A study was carried out to estimate the prevalence and associated factors of
      sexual intercourse among school adolescents in Coast Province, Kenya. Data were
      obtained through the Kenya Global School-Based Health Survey. Overall the
      prevalence of sexual intercourse within the last 12 months was 14.9% (22.2% in
      males and 5.0% in females). Among males, the protective factors against having
      sex were being of age < 15 years (OR = 0.60, 95% CI 0.58, 0.62) and ever been
      drunk (OR = 0.63, 95% CI 0.59, 0.67). The risk factors for having sex among males
      were ever smoked (OR = 2.05, 95% CI 1.92, 2.19), having close friends (OR = 1.68,
      95% CI 1.56, 1.81), currently drinking alcohol (OR = 1.13, 95% CI 1.06, 1.20),
      ever used drugs (OR = 2.36, 95% CI 2.24, 2.49) and parental supervision (OR =
      1.30, 95% CI 1.25, 1.34). Meanwhile among female respondents, parental
      supervision was protective (OR = 0.88, 95% CI 0.81, 0.94) and the only risk
      factor was ever used drugs (OR = 2.85, 95% CI 2.57, 3.15). It is suggested that
      public health interventions aimed to promote adolescent sexual health should be
      designed with the appreciation of the factors associated with sexual activity in
      due consideration.

PMID- 18087893
TI  - The quality of sputum smear microscopy diagnosis of pulmonary tuberculosis in Dar
      es Salaam, Tanzania.
AB  - This study was carried out to determine the rate of agreement or disagreement of
      microscopy reading and culture positivity rate among smear positixe and negative
      specimens between peripheral tuberculosis diagnostic centres (PDCs) and Central
      Reference luberculosis laboratory (CTRL). In this study 13 PDCs in Dar es Salaam,
      Tanzania were involved. Lot Quality Assurance Sampling (LQAS) method was used to
      collect 222 sputum smear slides. A total of 190 morning sputum specimens with
      corresponding slides were selected for culture. First readings were done by
      technicians at PDCs and thereafter selected slides and specimens were sent to
      CTRL for re-examination and culture. Culture results were used as a gold
      standard. Of 222 slides selected, 214 were suitable for re-examination.
      Percentage of agreement of smear reading between PDCs and CTRL was 42.9% and 100%
      for positive and negative slides, respectively. Measure of agreement (Kappa
      statistic) was 0.5, indicating moderate agreement. Of 190 samples cultured,
      percentage of agreement between smear reading from PDCs and CTRL was 37% and
      88.9% for smear positive and negative slides, respectively. Kappa statistic was
      0.3 indicating poor-fair agreements. Comparison of smear reading from PDCs with
      culture showed sensitivity of 36.9% and specificity of 88.9%. Comparison of smear
      readings from CTRL with culture results showed sensitivity of 95.6% and
      specificity of 98.6%. In conclusion there was inadequate performance in diagnosis
      of TB using smear microscopy among peripheral diagnostic centres in Dar es
      Salaam. This calls for immediate and rigorous measures to improve the quality of
      smear microscopy. It is therefore important to strengthen the capacity of
      laboratory personnel in smear microscopy techniques through supportive
      supervision and training.

PMID- 18087894
TI  - Knowledge and healthcare seeking behaviour of pulmonary tuberculosis patients
      attending Ilala District Hospital, Tanzania.
AB  - A cross-sectional study was conducted, based on systematic sampling of
      consecutive patients with pulmonary tuberculosis (TB) symptoms and who attended
      the TB clinic for their medication at Ilala District Hospital, Tanzania. The
      study sample comprised of 153 people who were almost equally distributed among
      men and women. Three quarters (75%) of the subjects were vaccinated against TB
      with the majority being 40 years and younger. Half the study subjects were
      diagnosed to have TB between the 2nd and 4th month after their symptoms appeared.
      A chest X-ray was used to initiate anti-TB therapy in half the subjects. No
      consistency was followed in the diagnostic procedures done to confirm the
      diagnosis. Over half the patients (54.3%) admitted that they openly speak about
      their illness to others but that only one-third (33.3%) of their friends and
      family responded in a considerate and sympathetic manner. One-third (36.6%) of
      the friends and relatives became less friendly and the remaining one-third openly
      portrayed fear and tried to discriminate the patient even after the commencement
      of medications. The patients' compliance rate was 100%. The counselling received
      from the health personnel and the patients' own motivations to improve their
      health, was the main driving force in seeking treatment and taking daily
      medication. Discrimination against TB patients by relatives and friends is likely
      to hinder positive health seeking behaviour and thus impede control of this
      disease.

PMID- 18087895
TI  - Onchocerciasis situation in the Tukuyu focus of southwest Tanzania after ten
      years of ivermectin mass treatment.
AB  - A purposive cross-sectional epidemiological study was conducted in the Tukuyu
      Onchocerciasis focus in south-western Tanzania in 2004, ten years after launching
      the ivermectin mass treatment programme, and 23 years after establishing focal
      parasite prevalence. The objective was to assess contemporary Onchocerciasis
      clinical and parasitological situation and assess community knowledge about the
      disease and its control. From historical data, five villages with high parasite
      prevalence were selected, two each on the Lufilyo and Kiwira Rivers and one on
      lower Lumbira River. Skin biopsies were taken from the iliac crest on the left
      and right buttocks, for examination of Onchocerca volvulus microfilariae.
      Onchocercal skin lesions were checked using natural light, while nodules were
      palpated from head to ankles and scored. A structured questionnaire was
      administered to participants. A total of 438 persons (age=16-99 years) were
      examined. No skin microfilariae (mf) were detected. Onchocercal skin symptoms
      were found in 170 (38.8%), of which 30 (6.9%) had nodules, 48 (11.0%) chronic
      onchodermatitis and 92 (21%) itching. One-third (34.5%) had correct knowledge
      that black flies ("tusunya") are vectors of onchocerciasis. Half of the
      respondents (n=217) confirmed taking ivermectin for onchocerciasis treatment, and
      428 (97.7%) were willing to continue for any duration. It is concluded that the
      undetectable skin microfilariae in the study sample was partly attributable to
      the consequences of ongoing ivermectin mass treatment. It is recommended that the
      control efforts, as well as monitoring and evaluation be sustained to determine
      its long term impact, and that a more sensitive technique be used to check O.
      volvulus skin mf prevalence.

PMID- 18087896
TI  - Placental malaria in Owerri, Imo State, south-eastern Nigeria.
AB  - Malaria in pregnancy jeopardizes the outcome of pregnancy, affecting both the
      mother and the foetus. The prevalence of placental malaria in women, who
      routinely attended ante-natal clinics in Owerri, south-eastern Nigeria, was
      assessed using three hospitals between March 2004 and August 2005. Placental
      blood was collected in EDTA bottles from incisions made on cleaned basal plate of
      the placenta, within an hour of delivery. Blood collected was used to assess ABO
      blood group, haemoglobin level as well as malaria parasitaemia. Malaria
      parasitaemia was determined from thick and thin smears stained with Giemsa, while
      the haemoglobin level was measured using the cyanomethaemoglobin method. A total
      of 586 pregnant women were involved in this study with written consents. Malaria
      parasites were observed in 175 (29.9%) of the women on delivery. Of these women,
      64 (36.6%) were anaemic. A significant relationship at P<0.05 variation, was
      observed between the prevalence of malaria parasites in the placenta and
      gravidity, age and blood group. The rate of occurrence of malaria parasitaemia,
      in the placenta of women who were on a weekly prophylaxis against malaria is
      alarming and calls for more serious efforts in the prevention of malaria
      especially in this vulnerable group.

PMID- 18087897
TI  - Antimicrobial susceptibility of Shigella flexneri and S. dysenteriae isolated
      from stool specimens of patients with bloody diarrhoea in Mwanza, Tanzania.
AB  - This study was conducted to determine frequency and pattern of antimicrobial
      susceptibility of Shigella species isolated from stool specimens collected from
      patients presenting with bloody diarrhoea in Mwanza City, Tanzania. The study was
      carried out from October 2004 to October 2005 and involved patients attending
      Sekou Toure Regional Hospital and Butimba Health Centre. Bacteriological cultures
      were done at the National Institute for Medical Research laboratory. A total of
      489 patients (median age = 20 years) participated in the study and were able to
      provide stool specimens. Shigella species were isolated from 14% (69/489) of the
      stool specimens collected. Of the sixty nine strains of Shigella spp isolated, 62
      (90%) were S. flexneri and 7 (10%) were S. dysenteriae. All Shigella strains
      isolated showed high resistance to ampicillin, tetracycline, trimethoprim
      sulphamethoxazole and chloramphenicol, drugs commonly used for management of
      shigellosis in Tanzania. However all isolates were fully susceptible to
      ciprofloxacin, nalidixic acid, erythromycin, cefuroxime and gentamycin. S.
      flexneri showed resistance to amoxy-clavulanic_acid and azithromycin in 5% and 2%
      of isolates, respectively. None of the S. dysenteriae isolates were resistant to
      these two drugs. Entamoeba histolytica, Giardia lamblia and Schistosoma mansoni
      were microscopically detected in 16.5%, 4.4% and 5.3% of patients, respectively.
      These findings suggest that there is a need to carry out extensive susceptibility
      studies in different parts of the country with view of re-appraising the current
      guidelines for management of bloody diarrhoea in Tanzania.

PMID- 18087898
TI  - Sex differences in prevalence rates and predictors of cigarette smoking among in
      school adolescents in Kilimanjaro, Tanzania.
AB  - An analysis of the Global Youth Tobacco Survey for Kilimanjaro, Tanzania was
      carried out to assess sex differences in the prevalence rates and predictors of
      current cigarette smoking among in-school adolescents. A total of 2323
      adolescents participated in the study of whom 53% were females and 47% males. The
      prevalence of current cigarette smoking was 3.0% and 1.4% among males and
      females, respectively. The common factors that were significantly positively
      associated with cigarette smoking between sexes were: having more pocket money,
      closest friend smoked cigarettes, seeing actors smoke on TV, videos or movies,
      and seeing advertisements for cigarettes at social gatherings. Seeing anti
      smoking messages at social gatherings were negatively associated with smoking
      among both sexes. While having had something such as a t-shirt or pen with a
      cigarette brand logo on it was positively associated with cigarette smoking among
      males, it was negatively associated with cigarette smoking among females. Male
      adolescents older than 15 years, those in their 9th year of schooling, and those
      who had seen cigarette brand names on TV were more likely to smoke. Meanwhile,
      male respondents who were in their 8th year of schooling, had seen anti-smoking
      media messages, and advertisements for cigarettes in newspapers or magazines were
      less likely to smoke. Among female adolescents, those who had parents who smoked,
      and surprisingly those who perceived that cigarette smoking as harmful were more
      likely to smoke. Interestingly, seeing advertisement for cigarettes on billboards
      was negatively associated with smoking among female adolescents. Interventions
      aimed to reduce adolescent smoking need to be designed and implemented with due
      consideration of sex differences in these associated factors.

PMID- 18087900
TI  - Suicidal ideation and associated factors among in-school adolescents in Zambia.
AB  - A cross sectional study was conducted to estimate the prevalence and correlates
      of suicidal ideation among in-school adolescents in Zambia. Backward logistic
      regression analysis was conducted to assess the association between relevant
      predictor variables and suicidal ideation within the last 12 months. A total of
      1970 in-school adolescents who participated in the Zambia Global School-Based
      Health Survey in 2004 responded to the question on suicidal ideation. Overall,
      54.0% were males, 40.8% were current drinkers, and 35.9% ever smoked marijuana
      (cannabis). Altogether 31.3% reported suicidal ideation in the past 12 months
      (males = 31.1%; females = 31.4%). Being male (OR = 1.05; 95%CI 1.03, 1.05): being
      <14 years old (OR = 1.21; 95%CI 1.19, 1.23), having been drunk (OR = 1.28; 95%CI
      1.27, 1.29). worried (OR= 1.05; 95%CI 1.04, 1.06), sad or hopeless in the past 12
      months (OR = 1.02; 95%CI 1.01, 1.03) and ever used marijuana (OR = 1.18; 95%CI
      1.17, 1.19) were positively associated with suicidal ideation. Loneliness
      appeared to be protective (OR = 0.92; 95%CI 0.91, 0.92). All the results, except
      for ever smoked marijuana and ever been drunk, may have been biased due to non
      response to the question on suicidal ideation. A series of cross sectional
      studies should be conducted to monitor changes in behavioural factors among
      others ever smoked marijuana and ever been drunk in order to broaden our
      understanding of factors that may be causing adolescents to seriously consider
      committing suicide.

PMID- 18087899
TI  - Low intensity laser therapy is comparable to bromocriptine-evening primrose oil
      for the treatment of cyclical mastalgia in Egyptian females.
AB  - One of the successful treatments for cyclical mastalgia is bromocriptine evening
      primrose combination. A double blind study was applied on 80 patients with
      cyclical mastalgia. They were randomly divided into two groups (A and B). In
      group A, patients were treated by bromocriptine/evening primrose. To group B,
      LILT with specified dosimetry was applied, using a device that delivers He-Ne
      laser combined with 4 infra-red diode laser. Evaluation of treatment was both
      subjective (using VAS) and objective (studying the degree of drop in plasma
      cortisol level). The drop of plasma cortisol with treatment was studied using the
      student -t distribution. A good response was observed in the laser group in
      82.5%, compared to 63.9% in the bromocriptine/evening primrose group. There was a
      significant deference before and after treatment in both groups (P<0.05). This
      difference was more for the drug treated group than for the laser treated group,
      but in the latter, it acted on a wider sector of patients. In conclusion, LILT is
      recommended as a new treatment modality for cyclical mastalgia.

PMID- 18087901
TI  - Knowledge on malaria transmission and its prevention among schoolchildren in
      Kyela District, south-western Tanzania.
AB  - A school-based study was carried out to assess the knowledge on malaria and its
      prevention among children in Kyela District, south-western, Tanzania in August
      September 2004. A total of 400 schoolchildren (age = 10-20 years) from four
      schools were selected. A structured questionnaire was used to collect data on
      knowledge on malaria transmission, methods of prevention, source of information
      and use of mosquito nets. More than 85% of the respondents were knowledgeable on
      malaria and preventive measures. Sources of information about malaria and its
      control were mainly from their teachers (47.4%), print materials (21.9%), family
      members (20.4%), television and radio (7.3%) and medical personnel (2.2.%). The
      perceived best control measures were untreated nets (32.1%), treated nets
      (21.4%), environmental management (25.7%) and burning mosquito coils and insect
      repellents (20.8%). Availability of mosquito nets was relatively high (70%), but
      only 38% of the pupils were using insecticide treated nets (ITNs). Low ITN use
      was due to its unavailability (57.5%), cost (35%) and foul smell and fear of side
      effects (7.5%). These findings suggest schoolchildren are aware about malaria and
      its prevention methods, but are not well-informed of the benefits of using ITNs.
      More education and advocacies on use of ITNs to parents and children is needed.

PMID- 18087902
TI  - Facing the challenges in human resources for humanitarian health.
AB  - The human resources crisis in humanitarian health care parallels that seen in the
      broader area of health care. This crisis is exacerbated by the lack of resources
      in areas in which humanitarian action is needed--difficult environments that
      often are remote and insecure--and the requirement of specific skill sets is not
      routinely gained during traditional medical training. While there is ample data
      to suggest that health outcomes improve when worker density is increased, this
      remains an area of critical under-investment in humanitarian health care. In
      addition to under-investment, other factors limit the availability of human
      resources for health (HRH) in humanitarian work including: (1) over-reliance on
      degrees as surrogates for specific competencies; (2) under-development and under
      utilization of national staff and beneficiaries as humanitarian health workers;
      (3) lack of standardized training modules to ensure adequate preparation for work
      in complex emergencies; (4) and the draining of limited available HRH from
      countries with low prevalence and high need to wealthier, developed nations also
      facing HRH shortages. A working group of humanitarian health experts from
      implementing agencies, United Nations agencies, private and governmental
      financiers, and members of academia gathered at Hanover, New Hampshire for a
      conference to discuss elements of the HRH problem in humanitarian health care and
      how to solve them. Several key elements of successful solutions were highlighted,
      including: (1) the need to develop a set of standards of what would constitute
      "adequate training" for humanitarian health work; (2) increasing the utilization
      and professional development of national staff; (3) "training with a purpose"
      specific to humanitarian health work (not simply relying on professional degrees
      as surrogates); (4) and developing specific health task-based competencies
      thereby increasing the pool of potential workers. Such steps would accomplish
      several key goals, such as: (1) more confidently ensuring that individuals hired
      for a given post would have the capacity to function at a commonly understood
      level of training; (2) greatly increasing the potential number and types of
      workers available for humanitarian work; (3) increasing the efficiency of human
      resources utilization in humanitarian projects; and (4) recognition that
      humanitarian work is a multi-disciplinary endeavor: these goals will contribute
      to ensuring that humanitarian health workers have a minimum training in broader
      humanitarian action, making them more effective team members in the field.
      Efforts were made to highlight some promising pilot programs for human resource
      development in humanitarian work, to identify a future vision for humanitarian
      health as a profession, and to develop a human resources strategy for achieving
      that vision.

PMID- 18087903
TI  - Professionalization of disaster medicine--an appraisal of criterion-referenced
      qualifications.
AB  - The landmark Humanitarian Response Review, commissioned by the United Nations
      Emergency Relief Coordinator in 2005, has catalyzed recent reforms in disaster
      response through the Inter-Agency Standing Committee. These reforms include a
      "cluster lead" approach to sectoral responsibilities and the strengthening of
      humanitarian coordination. Clinical medicine, public health, and disaster
      incident management are core disciplines underlying expertise in disaster
      medicine. Technical lead agencies increasingly provide pre-deployment training
      for selected health personnel. Moreover, technical innovations in disaster health
      sciences increasingly are disseminated to the disaster field through multi-agency
      initiatives, such as the Standardized Monitoring and Assessment of Relief and
      Transitions (SMART) initiative. The hallmark qualification of competency to
      render an informed opinion in the health specialties remains specialty board
      certification in North American healthcare traditions, or specialty society
      fellowship in British and Australasian healthcare traditions. However, disaster
      incident management training lacks international consensus on hallmark
      qualifications for competency. Disaster experience is best characterized in terms
      of months of full-time, hands-on field service. Future practitioners in disaster
      medicine will see intensified efforts to define competency benchmarks across
      underlying core disciplines as well as key field performance indicators.
      Quantitative decision-support tools are emerging to assist disaster planners and
      medical coordinators in their personnel selection.

PMID- 18087904
TI  - Non-governmental organizational health operations in humanitarian crises: the
      case for technical support units.
AB  - As the humanitarian health response industry grows, there is a need for technical
      health expertise that can build an evidence base around outcome measures and
      raise the quality and accountability of the health relief response. We propose
      the formation of technical support units (TSUs), entities of health expertise
      institutionalized within humanitarian non-governmental organizations (NGOs),
      which will bridge the gap between the demand for evidence-based, humanitarian
      programming and the field capacity to accomplish it. With the input of major
      humanitarian NGOs and donors, this paper discusses the attributes and capacities
      ofTSUs; and the mechanisms for creating and enhancing TSUs within the NGO
      management structure.

PMID- 18087905
TI  - Health tracking for improved humanitarian performance.
AB  - Presently, there is no shortage of methods for collecting data on populations
      requiring assistance from humanitarian health interventions. However, utilizing a
      working group, the authors of this paper have looked at these methods through a
      critical lens and found that there is need for improvement upon existing systems
      of data collection and analysis. The authors concluded that efforts to
      standardize the methods of data collection are needed to achieve universal
      uniformity, and that more funding should be allocated to analyze the data
      collected.

PMID- 18087906
TI  - Advances in monitoring have not translated into improvements in humanitarian
      health services.
AB  - BACKGROUND: This paper is an attempt to review the advances and shortfalls in
      data collection and use of health data that have occurred during health
      emergencies in recent decades for the opening session of the Humanitarian and
      Health Conference at Dartmouth University in September of 2006. METHODS: Examples
      of various kinds of successes and failures associated with health data collection
      are given to highlight advances with an effort to emphasize multi-agency efforts
      reviewed by outside scholars. RESULTS: Health data, particularly surveillance
      data, have allowed relief workers to set priorities for life-saving humanitarian
      programs. The main guidelines widely utilized such as those of the US Centers for
      Disease Control and Prevention, Medecins sans Frontieres, and the Sphere Project
      have considerable similarity due to the consistency of data collected in various
      crises. Moreover, difficult to see problems and successes have been revealed by
      coherent surveillance efforts. Yet, these data collection efforts can not show
      significant improvements in the quality of humanitarian aid in recent years.
      Moreover, health data often do not appear to have meaningful influence on the
      prioritizing of relief resources globally or on those political issues that
      trigger emergencies. CONCLUSIONS: The field of humanitarian relief is relatively
      nascent. Methods for documenting basic health measures on the local level have
      been developed and general health priorities have been documented. Some technical
      improvements in monitoring still are needed but decision-making is most often
      limited by the lack of data rather than the problems with data. The ability of
      health data to influence spending global priorities, legal or political actions
      undertaken by international organizations, remains very limited.

PMID- 18087907
TI  - Expanding the scope of humanitarian program evaluation.
AB  - The effectiveness of humanitarian programs normally is evaluated according to a
      limited number of pre-defined objectives. These objectives typically represent
      only selected positive expected impacts of program interventions and as such, are
      inadequate benchmarks for understanding the overall effectiveness of aid. This is
      because programs also have unexpected impacts (both positive and negative) as
      well as expected negative impacts and expected positive impacts beyond the
      program objectives. The authors contend that these other categories of program
      impacts also should be assessed, and suggest a methodology for doing so that
      draws on input from the perspectives of beneficiaries. This paper includes
      examples of the use of this methodology in the field. Finally, the authors
      suggest future directions for improving this type of expanded assessment and
      advocate for its widespread use, both within and without the field of disaster
      response.

PMID- 18087908
TI  - Measuring health program effectiveness in the field: an assessment tool.
AB  - To assist field workers in program evaluation and to explicitly discuss program
      strengths and weaknesses, a practical method to estimate the effectiveness of
      public health interventions within the existing program capacity was developed.
      The method and materials were tested in seven countries (Afghanistan, Zimbabwe,
      Tanzania, Uganda, Guatemala, the Philippines, and Ghana). In this method, four
      core components are assessed using a questionnaire: (1) the efficacy of the
      intervention; (2) the level of existing human resources (i.e., quality of
      recruitment, training, and continuing education); (3) the infrastructure (i.e.,
      supplies, salary, transportation, and supervision); and (4) the level of
      community support (i.e., access and demand). Using the assessment tool provided,
      program staff can determine if all necessary elements are in place for a
      successful program that can deliver the specific intervention. Based on the
      results of the assessment program, weaknesses can be identified, explicitly
      discussed, and addressed. The usefulness of this tool in humanitarian relief may
      be twofold: (1) to assess the design and implementation of effective programs;
      and (2) to highlight the inevitable need for capacity building as the disaster
      situation evolves.

PMID- 18087909
TI  - Information for disasters, information disasters, and disastrous information.
AB  - Information is needed to support humanitarian responses in every phase of a
      disaster. Participants of a multilateral working group convened to examine how
      best to meet these information needs. Although information systems based on
      routine reporting of diseases are desirable because they have the potential to
      identify trends, these systems usually do not deliver on their promise due to
      inadequate organization and management to support them. To identify
      organizational and management characteristics likely to be associated with
      successful information systems in disaster settings, evaluations of the
      Integrated Disease Surveillance and Response (IDSR) programs in 12 participating
      countries were reviewed. Characteristics that were mentioned repeatedly in the
      evaluations as associated with success were grouped into nine categories: (1)
      human resources management and supervision; (2) political support; (3)
      strengthened laboratory capacity; (4) communication and feedback (through many
      mechanisms); (5) infrastructure and resources; (6) system design and capacity;
      (7) coordination and partnerships with stakeholders; (8) community input; and (9)
      evaluation. Selected characteristics and issues within each category are
      discussed. Based on the review of the IDSR evaluations and selected articles in
      the published literature, recommendations are provided for improving the short-
      and long-term organization and management of information systems in humanitarian
      responses associated with disasters. It is suggested that information systems
      that follow these recommendations are more likely to yield quality information
      and be sustainable even in disaster settings.

PMID- 18087910
TI  - Enhancing collaboration during humanitarian response: an interim report from
      stakeholders survey.
AB  - The effectiveness of humanitarian response efforts has long been hampered by a
      lack of coordination among responding organizations. The need for increased
      coordination and collaboration, as well as the need to better understand
      experiences with coordination, were recognized by participants of a multilateral
      Working Group convened to examine the challenges of coordination in humanitarian
      health responses. This preliminary study is an interim report of an ongoing
      survey designed by the Working Group to describe the experiences of coordination
      and collaboration in greater detail, including factors that promote or discourage
      coordination and lessons learned, and to determine whether there is support for a
      new consortium dedicated to coordination. To date, 30 key informants have
      participated in 25-minute structured interviews that were recorded and analyzed
      for major themes. Participants represented 21 different agencies and
      organizations: nine non-governmental organizations, eight academic institutions,
      two donor organizations, the US Centers for Disease Control and Prevention, and
      the World Health Organization. Common themes that emerged included the role of
      donors in promoting coordination, the need to build an evidence base, the
      frequent occurrence of field-level coordination, and the need to build new
      partnerships. Currently, there is no consensus that a new consortium would be
      helpful. Addressing the underlying structural and professional factors that
      currently discourage coordination may be a more effective method for enhancing
      coordination during humanitarian responses.

PMID- 18087911
TI  - The dilemma of neutrality.
AB  - This paper focuses on the dilemma that humanitarian non-governmental
      organizations (NGOs) face in their efforts to gain access to populations caught
      up in current wars. Narrow and broad concepts of humanitarian protection are
      discussed and it is argued that despite high levels of professionalism, the space
      for humanitarian action has constricted sharply since the events surrounding the
      attacks of 11 September 2001. Increasingly, aid workers are now being viewed with
      suspicion as agents of the great powers and assertions of humanitarian neutrality
      are not heeded or rejected. Non-governmental organizations have evolved a range
      of options to address this problem, but there is an urgent need to work
      collectively to find more durable and coherent solutions.

PMID- 18087912
TI  - Dialogue is destiny: managing the message in humanitarian action.
AB  - During humanitarian response efforts, the mass media serves as the primary
      informational intermediary informing donors, policy makers, and the non-affected
      public. A lack of professional standards within the current culture of
      journalism, the politics of media ownership, and media manipulation by
      governments has distorted reporting on humanitarian crises, with possible
      detrimental effects on response efforts. Humanitarian response organizations must
      assume a proactive, leading role in the management and sharing of information
      with each other as well as with donors, policy makers, and the public. This will
      require working with the media as partners, as well as exploring innovative
      methods of mass communication. A multi-stakeholder, cooperative communication
      initiative could help improve media involvement, and harness the media as a
      credible and knowledgeable communication tool for response efforts. A
      professional publication dedicated to the discipline of humanitarian relief also
      could optimize efforts, communicate the perspectives of beneficiaries, and manage
      the underutilized resource of the general public.

PMID- 18087913
TI  - Medical care for a mass gathering: the Suwa Onbashira Festival.
AB  - INTRODUCTION: The Suwa Onbashira Festival is held every six years and draws
      approximately one million spectators from across Japan. Men ride the Onbashira
      pillars (logs) down steep slopes. At each festival, several people are crushed
      under the heavy log. During the 2004 festival, for the first time, a medical care
      system that coordinated a medical team, an emergency medical service, related
      agencies, and local hospitals was constructed. OBJECTIVE: The aims of this study
      were to characterize the spectrum of injuries and illness and to evaluate the
      medical care system of this festival. METHODS: The festival was held 02 April-10
      May 2004. The medical records of all of the patients who presented to an on-site
      medical tent or who were treated at the scene and transported to hospitals over a
      12-day period were reviewed. The following items were evaluated: (1) the
      emergency medical system at the festival; (2) the environmental circumstances;
      and (3) patient data. RESULTS: All medical usage rates are reported as patients
      per 10,000 attendees (PPTT). A total 1.8 million spectators attended the festival
      during the 12-day study period; a total of 237 patients presented to the medical
      tent (1.32 PPTT), and 63 (27%) were transferred to hospitals (0.35 PPTT). Of the
      total, 135 (57%) suffered from trauma--two were severely injured with pelvic and
      cervical spine fractures; and 102 (43%) had medical problems including heat
      related illness. CONCLUSIONS: Comprehensive medical care is essential for similar
      mass gatherings. The appropriate triage of patients can lead to efficient medical
      coverage.

PMID- 18087914
TI  - Financing hospital disaster preparedness.
AB  - Disaster preparedness and response have gained increased attention in the United
      States as a result of terrorism and disaster threats. However, funding of
      hospital preparedness, especially surge capacity, has lagged behind other
      preparedness priorities. Only a small portion of the money allocated for national
      preparedness is directed toward health care, and hospitals receive very little of
      that. Under current policy, virtually the entire funding stream for hospital
      preparedness comes from general tax revenues. Medical payers (e.g., Medicare,
      Medicaid, and private insurance) directly fund little, if any, of the current
      bill. Funding options to improve preparedness include increasing the current
      federal grants allocated to hospitals, using payer fees or a tax to subsidize
      preparedness, and financing other forms of expansion capability, such as mobile
      hospitals. Alternatively, the status quo of marginal preparedness can be
      maintained. In any event, achieving higher levels of preparedness likely will
      take the combined commitment of the hospital industry, public and private payers,
      and federal, state, and local governments. Ultimately, the costs of preparedness
      will be borne by the public in the form of taxes, higher healthcare costs, or
      through the acceptance of greater risk.

PMID- 18087915
TI  - Task force St. Bernard: operational issues and medical management of a National
      Guard disaster response operation.
AB  - After Hurricane Katrina struck the Gulf Coast of the United States on 29 August
      2005, it became obvious that the country was facing an enormous national
      emergency. With local resources overwhelmed, governors across the US responded by
      deploying thousands of National Guard soldiers and airmen. The National Guard has
      responded to domestic disasters due to natural hazards since its inception, but
      an event with the magnitude of Hurricane Katrina was unprecedented. The
      deployment of >900 Army National Guard soldiers to St. Bernard Parish, Louisiana
      in the aftermath of the Hurricane was studied to present some of the operational
      issues involved with providing medical support for this type of operation. In
      doing so, the authors attempt to address some of the larger issues of how the
      National Guard can be incorporated into domestic disaster response efforts. A
      number of unforeseen issues with regards to medical operations, medical supply,
      communication, preventive medicine, legal issues, and interactions with civilians
      were encountered and are reviewed. A better understanding of the National Guard
      and how it can be utilized more effectively in future disaster response
      operations can be developed.

PMID- 18087916
TI  - Preparing for burn disasters: predictors of improved perceptions of competency
      after mass burn care training.
AB  - INTRODUCTION: Prehospital and community hospital healthcare providers in the
      United States must be prepared to respond to burn disasters. Continuing education
      is the most frequently utilized method of updating knowledge, skills, and
      competence among healthcare professionals. Since preparedness training must meet
      multiple educational demands, it is vital to understand how participants' work
      and educational experience and the program's content and delivery methods impact
      knowledge acquisition, and how learning influences confidence and competence to
      perform new skills. PURPOSE: The purpose of this exploratory, convenience sample
      study was to identify healthcare provider characteristics and continuing
      education training content areas that were predictive of self-reported
      improvement in competence after attending a mass-casualty burn disaster
      continuing education program. METHODS: Logistic regression analysis of data from
      a post-training evaluation from nine, one-day continuing education conferences on
      mass burn care was used to identify factors associated with improved self
      reported competency to respond to mass burn casualties. RESULTS: The following
      factors were associated most closely with increased self-reported competency: (1)
      prehospital work setting (odds ratio (OR) = 3.06, confidence interval (CI) = 0.83
      11.30, p = 0.09); (2) 11 or more years of practice (OR = 0.31, CI = 0.09-1.08, p
      = 0.07); and (3) practice in an urban setting (OR = 0.01, CI = 0.18-0.82, p <
      0.01). Confidence items included: (1) ability to implement appropriate airway
      management modalities (OR = 2.31, CI = 1.03-5.17, p < 0.04); (2) manage patients
      with electrical injuries (OR = 4.86, CI = 1.84-12.85, p < 0.001); (3) identify
      non-survivable injuries (OR = 2.24, CI = 0.93-5.43, p = 0.07); and (4) recognize
      special problems associated with burns in young children or older adults (OR =
      2.14, CI = 0.87-5.23, p = 0.10). The final model explained 89.9% of the
      variability in self-reported competence. CONCLUSIONS: Interventions used to train
      healthcare providers for burn disasters must cover a broad range of topics.
      However, learning needs may vary by practice setting, work experience, and
      previous exposure to disaster events. This evaluation research provides three
      fold information for continuing education research: (1) to identify content areas
      that should be emphasized in future burn care training; (2) to be used as a model
      for CE evaluation in other domains; and (3) to provide support that many factors
      must be considered when designing a CE program. Results may be useful to others
      who are planning CE training programs.

PMID- 18087917
TI  - Usefulness of a DSM criteria-based inventory for screening for post-traumatic
      stress disorder.
AB  - The aim of the study is to evaluate the self-administered Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition criteria-based inventory for
      the screening of post-traumatic stress disorder. Due to its low sensitivity (57%)
      and high specificity (88%), it could be useful as a second step of a screening
      procedure in combination with other validated, self-report instruments. The
      clinical implications of the findings and the limitations of the study are
      discussed.

PMID- 18087918
TI  - Psychological trauma in a relief worker--a case report from earthquake-struck
      areas of north Pakistan.
AB  - Vicarious traumatization is now a well-known entity and may have negative
      influences on those that are involved in rescue efforts in any disaster or
      traumatic events. Healthcare workers work with trauma survivors and witness an
      immense array of gruesome and ghastly images. This work has the potential to
      cause those engaged in rescue efforts to become affected subconsciously. Job
      related stress may cause psychological symptoms in care providers who provide
      support and listen to the survivors' account of trauma. A therapist working in
      disaster situations may become a victim of psychological anguish--undermining
      their physical and mental well-being as well as their profession, adversely
      affecting their traumatized patients, and leading to a counter-productive
      therapist-survivor relationship. This significant theme of secondary trauma must
      be recognized in relief workers at early stages and must be addressed at an
      individual as well as organizational level. The key may lie in turning to social
      supports, adapting positive coping mechanisms, and subsequently seeking mental
      health consultation. Further research is required in this area to determine the
      best resolution.

PMID- 18087919
TI  - Preliminary investigation into the role of physiotherapists in disaster response.
AB  - INTRODUCTION: Increasingly, disasters and disaster response have become prominent
      issues in recent years. Despite their involvement, there have been almost no
      investigations into the roles of physiotherapists in emergency disaster
      responses. Additionally, physiotherapists are not employed in emergency disaster
      response by many of the principal non-governmental organizations supplying such
      care, although they are included in military responses in the United States and
      United Kingdom, and in Disaster Medical Assistance Teams in the US. This paper,
      based on a small qualitative study, focuses on the potential role and nature of
      input of physiotherapists in disaster response. METHODS: A qualitative approach
      was chosen due to the emergent nature of the phenomenon. Four physiotherapists,
      all of whom had been involved in some type of disaster response, agreed to
      participate. Semi-structured telephone interviews were used to explore
      participants' experiences following disaster response, and to gain ideas about
      future roles for physiotherapists. Interviews were recorded, transcribed, and
      later analyzed using coding and categorization of data. RESULTS: Four main themes
      emerged: (1) descriptions of disasters; (2) current roles of the physiotherapist;
      (3) future roles of physiotherapists; and (4) overcoming barriers. Although all
      four physiotherapists had been ill-prepared for disaster response, they took on
      multiple roles, primarily in organization and treatment. However, participants
      identified several barriers to future involvement, including organizational and
      professional barriers, and gave suggestions for overcoming these. CONCLUSIONS:
      The participants had participated in disaster response, but in ill-defined roles,
      indicating a need for a greater understanding of disaster response among the
      physiotherapy community and by organizations supplying such care. The findings of
      this study have implications for such organizations in terms of employing skilled
      physiotherapists in order to improve disaster response. In future disasters,
      physiotherapy will be of benefit in treating and preventing rescue worker injury
      and treating musculoskeletal, critical, respiratory, and burn patients.

PMID- 18087920
TI  - Understanding barriers to emergency care in low-income countries: view from the
      front line.
AB  - INTRODUCTION: Morbidity and mortality due to acute but treatable conditions
      remain high in the developing world, as many significant barriers exist to
      providing emergency medical care. This study investigates these barriers in a
      rural region of Ethiopia. HYPOTHESIS: The limited capacity of frontline
      healthcare workers to diagnose and treat acute medical and surgical conditions
      represents a major barrier to the provision of emergency care in rural Ethiopia.
      METHODS: Health providers at a convenience sample of 16 rural health centers in
      the state of Tigray, Ethiopia completed a questionnaire designed to assess the
      availability of diagnostic and treatment modalities, the proximity and methods of
      transportation to referral facilities, and health providers' level of comfort in
      diagnosing and treating a variety of representative emergency medical conditions.
      RESULTS: Thirteen (81%) providers had only a very basic level of medical
      training, and seven (44%) lacked access to any diagnostic equipment. While most
      providers could offer oral rehydration solution (ORS), anti-pyretic medications,
      and antibiotics, none of the providers could offer blood transfusions or any form
      of surgery. Ten (63%) respondents stated that their patients had to travel >10 km
      from the health center to a referral hospital, with only a minority of patients
      having access to motorized transport. For the seven emergency conditions
      assessed, a majority of providers felt comfortable diagnosing these conditions,
      though fewer felt comfortable treating them. CONCLUSION: There is a significant
      need for both health worker training and improvements in transportation
      infrastructure in order to increase access to emergency medical care in rural
      areas of the developing world. Low-cost interventions that improve human capacity
      in a context-appropriate manner are warranted as transportation and hospital
      network capacity expansions are considered.

PMID- 18087921
TI  - The compliant dental office.

PMID- 18087922
TI  - Model exposure control plan for the dental office.

PMID- 18087923
TI  - HIPAA--where are we now?

PMID- 18087924
TI  - Periodontics: 6. The management of gingival recession.
AB  - Gingival recession is a common condition affecting the dentition. This paper
      describes the aetiology of gingival recession and discusses the appropriate
      management of this condition. CLINICAL RELEVANCE: Careful examination to detect
      gingival recession, or the factors that may place the patient at risk for
      recession, are important for prevention.

PMID- 18087925
TI  - The eating disorders: 1. Current scientific understanding and dental
      implications.
AB  - The eating disorders are a group of related but distinct disturbances in eating
      behaviour with wide-ranging effects. This first part describes the epidemiology,
      aetiology, general clinical features and specific dental sequelae associated with
      the eating disorders. Part 2 discusses psychological aspects of management as
      well as dental treatment. CLINICAL RELEVANCE: Dental health can be compromised in
      patients with an eating disorder. Dentists should understand the medical,
      psychological and dental features and competently manage any secondary dental
      problems.

PMID- 18087926
TI  - Early childhood caries--a review.
AB  - Early childhood caries (ECC) is rampant caries of the primary dentition of
      infants and toddlers. It represents a serious problem in dentistry as it
      progresses rapidly and affects young children. There is a need to identify risk
      factors for ECC so that targeted, cost-effective interventions can be designed.
      The literature indicates that immediate intervention is necessary to prevent
      further dental destruction, as well as more widespread health problems. CLINICAL
      RELEVANCE: Currently, some 4 out of 10 children starting school have decay in
      their primary dentition. It is prudent for dentists who diagnose ECC to provide
      therapy or, if treatment is not possible as a result of the young age of the
      child and limited co-operation, then it is important to refer the patient to an
      appropriately trained individual for therapy.

PMID- 18087927
TI  - Compliance: getting the most from your orthodontic patients.
AB  - Successful orthodontic treatment is highly dependent on optimal levels of patient
      compliance. This paper outlines methods that can be used by orthodontists and
      general practitioners to optimize compliance throughout active treatment and into
      the retention phase. CLINICAL RELEVANCE: Demand for orthodontic treatment is ever
      increasing. A compliant patient expedites successful treatment and minimizes the
      possibility of deleterious effects of appliances.

PMID- 18087929
TI  - Issues in dental outreach teaching--an introduction for the primary care
      practitioner.
AB  - Outreach teaching programmes can be organized in a variety of settings, be
      structured in different formats and can offer education and training to all
      members of the dental team. This paper principally examines outreach teaching as
      a contributory training experience for undergraduate dental students. Following a
      review of recent literature on the subject, educational and NHS host perspectives
      are considered in relation to a qualitative report on a contemporary programme
      offering training in Adult Restorative Care. CLINICAL RELEVANCE: Outreach
      training in a primary care setting offers undergraduate dental students
      complementary educational exposure to a real-life working environment.

PMID- 18087928
TI  - Lingual mucosal ulceration with mandibular sequestration.
AB  - Lingual mucosal ulceration with mandibular sequestration is a condition that
      presents most commonly in the lower molar region and may be influenced by a
      variety of local and systemic factors. Three such cases are reported, two
      involving a history of recent dental extraction and one of seemingly spontaneous
      onset with the possibility of an underlying association with bisphosphonate
      therapy. An overview of the surgical and non-surgical management strategies for
      such cases is described. CLINICAL RELEVANCE: This condition presents most
      commonly following extraction of mandibular molar teeth. Patients may require
      referral to secondary care for further management if failing to respond to local
      non-surgical measures or in the presence of underlying systemic factors.

PMID- 18087930
TI  - Bilateral presentation of necrotizing sialometaplasia--a case report.
AB  - Necrotizing sialometaplasia is a benign, self-limiting condition that may
      clinically and microscopically closely resemble mucoepidermoid carcinoma or
      squamous carcinoma with the potential for extensive, inappropriate and
      unnecessary treatment. This paper reports a case of bilateral necrotizing
      sialometaplasia of the palate which resolved quickly with conservative treatment
      only. CLINICAL RELEVANCE: The importance of necrotizing sialometaplasia is that
      this self-limiting condition may be mistaken for malignancy. It is important to
      recognize this condition to prevent unnecessary investigations and treatment
      being carried out.

PMID- 18087931
TI  - The surgical management of the oral soft tissues: 2. Surgical technique.
AB  - Adopting the correct surgical technique in minor oral surgery not only ensures
      that the end result of tooth removal is achieved, but that the patient is not put
      under any unnecessary harm during the procedure. This paper will cover the
      surgical techniques and skills required to perform the most commonly required
      mucoperiosteal flaps in general practice. CLINICAL RELEVANCE: Revision of the
      basic techniques is important to improve confidence and increase the amount of
      simple oral surgery performed in practice.

PMID- 18087932
TI  - Physical signs for the general dental practitioner. Case 49. Zidovudine (AZT or
      Retrovir) treatment.

PMID- 18087933
TI  - Aspects of human disease.

PMID- 18087934
TI  - Mycobacteriosis in companion psittacine birds: a review.
AB  - Mycobacteriosis has long been recognized as a disease of companion psittacine
      birds. In this review, the signalment, clinical signs of disease, and diagnosis
      of mycobacteriosis in psittacine birds are presented. Although treatment of birds
      with mycobacteriosis is controversial, therapeutic protocols for use in
      psittacine birds have been developed based on protocols used in humans. Results
      of recent studies indicate that mycobacteriosis in psittacine birds is unlikely
      to represent a significant health risk for humans. However, the potential for
      zoonotic disease must be considered, especially if persons who are
      immunocompromised are in contact with an infected bird.

PMID- 18087935
TI  - Repair of a coracoid luxation and a tibiotarsal fracture in a bald eagle
      (Haliaeetus leucocephalus).
AB  - A 4.5-kg, adult bald eagle (Haliaeetus leucocephalus) was presented after being
      found unable to fly. Crepitus was palpated in the left shoulder; however, the
      wing position was normal. Radiographs revealed caudoventral luxation of the left
      coracoid, affecting its distal articulation with the clavicle and its proximal
      articulation with the sternum. The luxation affecting the coracoid-sternum
      articulation was repaired by using a 4-hole, 1.5-mm T-plate and a 6-hole, 2.0-mm
      dynamic compression plate (DCP) placed side by side. The luxation affecting the
      coracoid and the clavicle was repaired by 2 cerclage wires in a simple
      interrupted pattern. Before a scheduled release, the bird sustained a closed,
      complete mid diaphyseal transverse fracture of the right tibiotarsus, which most
      likely occurred during recapture from the flight cage. The fracture was
      surgically repaired with 2 circumferential cerclage wires, an intramedullary
      Kirschner wire and one 10-hole, 2.7-mm DCP. The bird was successfully released,
      105 days after the first surgery, near the location where it was found.

PMID- 18087936
TI  - Magnetic resonance imaging is superior to radiography in evaluating spinal cord
      trauma in three bald eagles (Haliaeetus leucocephalus).
AB  - Three bald eagles (Haliaeetus leucocephalus) found along highways and unable to
      fly were presented for evaluation. All eagles exhibited sternal recumbency, as
      well as flaccid hind limb and tail paralysis. Vertebral column and spinal cord
      trauma were suspected as the cause. One bird died, whereas the remaining 2 birds
      were stabilized for diagnostic imaging studies. All 3 birds were evaluated by
      radiography and magnetic resonance imaging (MRI) for diagnosis and for prognosis
      in the live birds. Radiographic findings in all 3 birds were inconclusive,
      whereas MRI results showed extensive damage of the spinal cord and vertebral
      column, precluding functional recovery. The 2 surviving birds were euthanatized.
      In all birds, MRI assessments correlated well with necropsy and histopathologic
      findings.

PMID- 18087937
TI  - Disseminated mycobacteriosis in a bald eagle (Haliaeetus leucocephalus).
AB  - A mature bald eagle (Haliaeetus leucocephalus) was diagnosed with mycobacterial
      infection after being presented for an inability to fly, emaciation, and a
      swelling of the left tibiotarsal-tarso metatarsal joint. Results of a complete
      blood cell count revealed a persistent, marked leukocytosis, with heterophilia,
      monocytosis, and anemia. Radiographs revealed lysis of the left distal
      tibiotarsus and soft-tissue swelling around the left tibiotarsal-tarsometatarsal
      joint, multiple pulmonary opacities, and an enlarged liver. Endoscopic evaluation
      and biopsy of caseated material within the left caudal coelom revealed acid-fast
      organisms. The eagle was euthanatized, and results of necropsy and histologic
      evaluation revealed caseated granulomas of the intestine, lungs, air sacs, and
      subcutaneous regions of the hock. Results of culture, a polymerase chain reaction
      testing, and direct deoxyribonucleic acid (DNA) sequencing for mycobacterial 16S
      ribosomal ribonucleic acid DNA determined this organism most likely to be
      Mycobacterium avium.

PMID- 18087938
TI  - Lymphoplasmacytic myenteric, subepicardial, and pulmonary ganglioneuritis in four
      nonpsittacine birds.
AB  - A disease condition with clinical and pathologic findings compatible with
      psittacine proventricular dilatation disease was diagnosed in a canary (Serinus
      canaria), a greenfinch (Carduelis chloris), a long-wattled umbrellabird
      (Cephalopterus penduliger), and a bearded barbet (Lybius dubius). The canary and
      the greenfinch were kept as pets by different owners, whereas the bearded barbet
      and the long-wattled umbrellabird were kept in separate mixed species enclosures
      at the Barcelona Zoo. Clinical signs were variable in all 4 birds and included
      polyphagia, weight loss, weakness, and ataxia. Postmortem examination findings
      were also variable and included emaciation, hepatic and renal atrophy or
      enlargement, gallbladder dilatation, and intestinal and ventricular dilatation.
      Histopathologic lesions in all birds consisted of multifocal lymphoplasmacytic
      infiltration of myenteric and cardiac nerves and ganglia. These lesions are
      characteristic of proventricular dilatation disease of psittacine birds.

PMID- 18087939
TI  - Use of isoxsuprine for treatment of clinical signs associated with presumptive
      atherosclerosis in a yellow-naped Amazon parrot (Amazona ochrocephala
      auropalliata).
AB  - A 35-year-old yellow-naped Amazon parrot (Amazona ochrocephala auropalliata) was
      presented for gradually increasing inappetence, ataxia, weakness, and lethargy.
      Radiographic and ultrasonographic findings were strongly suggestive of
      atherosclerosis. Isoxsuprine, a peripheral vasodilator demonstrated to be of
      benefit in humans with intermittent limb pain, weakness, and lameness secondary
      to occlusive vascular disease, was selected for treatment. The bird's clinical
      signs resolved during treatment but recurred after varying periods of time when
      the medication was stopped intermittently. Nearly 3 years after the initial
      examination, the parrot was doing well on isoxsuprine therapy, with normal
      prehension of food with its feet and no recurrence of clinical signs.

PMID- 18087940
TI  - Baylisascaris procyonis infection in a Moluccan cockatoo (Cacatua moluccensis).
AB  - An adult female Moluccan cockatoo (Cacatua moluccensis) was evaluated for a 10
      day history of progressive ataxia and weakness. The bird had been exposed
      intermittently over a 3-day period to a cage that had previously housed juvenile
      raccoons. Results of diagnostic tests were inconclusive and, despite supportive
      care, the bird died 7 days after the initial presentation. Histopathologic
      examination revealed a single nematode larva in the midbrain that was consistent
      with Baylisascaris species and multifocal granulomas in the left ventricle of the
      heart. The neurologic disease in this bird was attributed to encephalitis caused
      by neural larval migration of the raccoon roundworm, Baylisascaris procyonis.

PMID- 18087941
TI  - The pros and cons of selling unweaned baby birds.

PMID- 18087942
TI  - What is your diagnosis? Fungal rhinosinusitis, with almost complete destruction
      of the premaxilla and deformation of the upper beak.

PMID- 18087943
TI  - A practical solution to the pervasive problems of p values.
AB  - In the field of psychology, the practice of p value null-hypothesis testing is as
      widespread as ever. Despite this popularity, or perhaps because of it, most
      psychologists are not aware of the statistical peculiarities of the p value
      procedure. In particular, p values are based on data that were never observed,
      and these hypothetical data are themselves influenced by subjective intentions.
      Moreover, p values do not quantify statistical evidence. This article reviews
      these p value problems and illustrates each problem with concrete examples. The
      three problems are familiar to statisticians but may be new to psychologists. A
      practical solution to these p value problems is to adopt a model selection
      perspective and use the Bayesian information criterion (BIC) for statistical
      inference (Raftery, 1995). The BIC provides an approximation to a Bayesian
      hypothesis test, does not require the specification of priors, and can be easily
      calculated from SPSS output.

PMID- 18087944
TI  - A theory of variability discrimination: finding differences.
AB  - Visual variability discrimination requires an observer to categorize collections
      of items on the basis of the variability in the collection; such discriminations
      may be vital to the adaptive actions of both humans and other animals. We present
      a theory of visual variability discrimination that aggregates localized
      differences between nearby items, and we compare this finding differences model
      with a previously proposed positional entropy model across several data sets
      involving both people and pigeons. We supplement those previously published data
      sets with four new experiments, three of which involve arrays comprising items
      entailing systematic, quantitative differences. Although both theories provide
      strong and similar fits of the published data sets, only the finding differences
      model is applicable to investigations involving quantitative item differences,
      providing excellent fits in these new experiments.

PMID- 18087945
TI  - Similarity, distance, and categorization: a discussion of Smith's (2006) warning
      about "colliding parameters".
AB  - The idea that categorization decisions rely on subjective impressions of
      similarities between stimuli has been prevalent in much of the literature over
      the past 30 years and has led to the development of a large number of models that
      apply some kind of decision rule to similarity measures. A recent article by
      Smith (2006) has argued that these similarity-choice models of categorization
      have a substantial design flaw, in which the similarity and the choice components
      effectively cancel one another out. As a consequence of this cancellation, it is
      claimed, the relationship between distance and category membership probabilities
      is linear in these models. In this article, I discuss these claims and show
      mathematically that in those cases in which it is sensible to discuss the
      relationship between category distance and category membership at all, the
      function relating the two is approximately logistic. Empirical data are used to
      show that a logistic function can be observed in appropriate contexts.

PMID- 18087946
TI  - Implicit memory influences the allocation of attention in visual cortex.
AB  - The visual environment is highly regular, with particular objects frequently
      appearing in specific locations. Previous studies of visual search have shown
      that people take advantage of such regularities, detecting targets more quickly
      when they appear at a predictable location within a given spatial configuration.
      Moreover, this effect depends on implicit rather than explicit memory for the
      configurations. These studies have suggested that implicit long-term memory for
      contextual information influences the allocation of attention, modulating the
      flow of information through visual cortex. The present study used event-related
      potentials to provide the first direct support for this proposal. We suggest that
      this guidance of attention by implicit memory is important in the natural
      environment because it allows environmental regularities to influence perception
      without the intervention of limited-capacity conscious processes.

PMID- 18087947
TI  - Individual differences in working memory capacity and visual search: the roles of
      top-down and bottom-up processing.
AB  - Individual differences in working memory capacity (WMC) have been implicated in a
      variety of top-down, attention-control tasks: Higher WMC subjects better ignore
      irrelevant distractions and withhold habitual responses than do lower WMC
      subjects. Kane, Poole, Tuholski, and Engle (2006) recently attempted to extend
      these findings to visual search, but found no relation between WMC and search
      efficiency, even in difficult tasks yielding steep search slopes. Here we used a
      visual search task that isolated the contributions of top-down versus bottom-up
      mechanisms, and induced a habitual response via expectation. Searches that relied
      primarily on bottom-up mechanisms did not vary with WMC, but searches that relied
      primarily on top-down mechanisms showed an advantage for higher over lower WMC
      subjects.

PMID- 18087948
TI  - Finding a new target in an old display: evidence for a memory recency effect in
      visual search.
AB  - Visual search often involves searching the same environment, consecutively, for a
      number of different targets. Here we investigate the extent to which search
      benefits from such previous exposure. In the experiment participants searched the
      same display consecutively for two different targets. Manual responses were
      faster in the second search than the first search regardless of whether a target
      was present or absent in the second search. Eye movement recordings demonstrated
      that the time necessary to find a target letter in the second search depended on
      when that letter was last fixated in the previous search. This fixation recency
      effect lasted for about four fixations. In addition, when a target was absent
      during the second search, participants were less likely to refixate a distractor
      if it had been recently fixated in the previous search and refixations tended to
      also occur later on in the search. These results provide evidence for a limited
      capacity short-term memory store in this kind of visual search.

PMID- 18087949
TI  - Eye movements and time-based selection: where do the eyes go in preview search?
AB  - In visual search tasks, presenting one set of distractors (previewing them)
      before a second set which contains the target, improves search efficiency
      compared to when all items appear simultaneously. It has been proposed that this
      preview benefit reflects an attentional bias against old information and toward
      new information. Here we tested directly whether there was such a bias by
      measuring eye movement behavior. The main findings were that fixations were
      biased against, and overall dwell times were shorter on, old stimuli during
      search in the preview condition. In addition, the initial onset of search was
      delayed in the preview condition and saccades made during the preview period did
      not disrupt the ability to prioritize new items. The data demonstrate directly
      that preview search results in an attentional bias toward new items and against
      old items.

PMID- 18087950
TI  - A direct test of the unequal-variance signal detection model of recognition
      memory.
AB  - Analyses of the receiver operating characteristic (ROC) almost invariably suggest
      that, on a recognition memory test, the standard deviation of memory strengths
      associated with the lures (sigma(lure)) is smaller than that of the targets
      (sigma(target)). Often, sigma(lure)/ sigma(target) approximately = 0.80. However,
      that conclusion is based on a model that assumes that the memory strength
      distributions are Gaussian in form. In two experiments, we investigated this
      issue in a more direct way by asking subjects to simply rate the memory strengths
      of targets and lures using a 20-point or a 99-point strength scale. The results
      showed that the standard deviation of the ratings made to the targets (S(target))
      was, indeed, larger than the standard deviation of the ratings made to the lures
      (S(lure)). Moreover, across subjects, the ratio S(lure)/ S(target) correlated
      highly with the estimate of sigma(lure)/ sigma(target) obtained from ROC
      analysis, and both estimates were, on average, approximately equal to 0.80.

PMID- 18087951
TI  - The revelation effect: moderating influences of encoding conditions and type of
      recognition test.
AB  - In the revelation effect, slowly revealing a test item immediately prior to a
      recognition judgment increases the probability of an "old" response. Extant
      accounts imply that the revelation effect occurs for familiarity-based judgments
      but not for those involving recall or recollection. To assess this implication,
      the contribution of recollection was varied by encoding conditions and memory
      tests. Two manipulations of recollection, semantic encoding and context-item
      integration, both reduced the revelation effect on a standard recognition test.
      For the same encoding conditions, a perceptually driven memory test (rhyme
      recognition) exhibited no revelation effect whatsoever. In a second experiment,
      the rhyme recognition test exhibited a revelation effect under impoverished
      encoding conditions. The results document important limits of the revelation
      effect produced by both encoding and test conditions. Furthermore, the
      recollection-based limitations of the revelation effect are not restricted to
      conditions of enhanced semantic encoding.

PMID- 18087952
TI  - The mixed truth about frequency effects on free recall: effects of study list
      composition.
AB  - The mixed-list paradox is the finding that high-frequency words show a recall
      advantage in blocked lists, but that this advantage is reversed or nullified in
      mixed lists. We argue that this paradox has been poorly defined. Specifically,
      researchers should investigate random and alternating lists separately. We
      examine blocked, random, and alternating lists in our experiment. We hypothesize
      that a low-frequency recall advantage could arise due to asymmetrically strong
      links between low- and high-frequency words. Supporting our hypothesis, a low
      frequency recall advantage is observed in the random list, as is an asymmetry of
      association. In the alternating list, no recall advantage is observed, and
      neither is any asymmetry of association. Our results offer a clear challenge to
      future research to (1) consider the associations between word frequencies and (2)
      consider random and alternating lists separately.

PMID- 18087953
TI  - Determinants of confirmation.
AB  - Epistemologists often suppose that the extent to which evidence e confirms
      hypothesis H depends on probabilities involving e and H, and nothing more. We
      show experimentally that human reasoners sometimes violate this assumption.

PMID- 18087954
TI  - Who is susceptible to conjunction fallacies in category-based induction?
AB  - Recent evidence suggests that the conjunction fallacy observed in people's
      probabilistic reasoning is also to be found in their evaluations of inductive
      argument strength. We presented 130 participants with materials likely to produce
      a conjunction fallacy either by virtue of a shared categorical or a causal
      relationship between the categories in the argument. We also took a measure of
      participants' cognitive ability. We observed conjunction fallacies overall with
      both sets of materials but found an association with ability for the categorical
      materials only. Our results have implications for accounts of individual
      differences in reasoning, for the relevance theory of induction, and for the
      recent claim that causal knowledge is important in inductive reasoning.

PMID- 18087955
TI  - Effects of time pressure on context-sensitive property induction.
AB  - Past research suggests that category-based induction flexibly draws on different
      kinds of knowledge in different contexts, and that different kinds of knowledge
      may differ in accessibility. The present study investigates the degree to which
      knowledge accessibility mediates context-sensitive induction by examining the
      effects of time pressure on inferences about novel properties of animal species.
      Participants were told about a novel gene or a novel disease that was true of one
      category of animals, then rated the likelihood that taxonomically, ecologically,
      and unrelated animals had the same property, under speeded or delayed conditions.
      Property effects were observed for taxonomically related species independent of
      time pressure, but were only observed for ecologically related species in the
      delayed condition. These results suggest that time pressure selectively restricts
      access to ecological knowledge, and that knowledge access is critical for context
      sensitive inductive reasoning.

PMID- 18087956
TI  - Sequential processing of cues in memory-based multiattribute decisions.
AB  - When probabilistic inferences have to be made from cue values stored in long-term
      memory, many participants appear to use fast and frugal heuristics, such as "take
      the best" (TTB), that assume sequential search of cues. A simultaneous global
      matching process with cue weights that are appropriately chosen would mimic the
      decision outcomes, albeit assuming different cognitive processes. We present a
      reanalysis of response times (RTs) from five published experiments (n=415) and
      one new experiment (n=82) that support the assumption of sequential search. In
      all instances in which decision outcomes indicated the use of TTB's decision
      rule, decision times increased monotonically with the number of cues that had to
      be searched in memory. Furthermore, RT patterns fitted the outcome-based strategy
      classifications, which further validates both measures.

PMID- 18087957
TI  - Who do you look like? Evidence of facial stereotypes for male names.
AB  - The present research provides evidence that people use facial prototypes when
      they encounter different names. In Experiment 1, participants created face
      exemplars for fifteen common male names, subsets of which were endorsed as good
      examples by a second set of participants. These most typical faces were morphed
      to create face-name prototypes. In Experiment 2, participants matched one of the
      names to each of the prototype faces from Experiment 1. Participants' matching
      choices showed convergence in naming the prototypes for many of the names.
      Experiment 3 utilized these same prototypes in a learning task designed to
      investigate if the face-name associations revealed in Experiment 2 impacted the
      learnability of the names. Participants learned face-name pairings that had a
      higher association (based on frequencies from Experiment 2) faster than pairings
      with a low association. Results suggest a more direct relationship between faces
      and names than has been previously proposed.

PMID- 18087958
TI  - A negative compatibility effect in priming of emotional faces.
AB  - The negative compatibility effect (NCE) is the surprising result that low
      visibility prime arrows facilitate responses to opposite-direction target arrows.
      Here we compare the priming obtained with simple arrows to the priming of
      emotions when categorizing human faces, which represents a more naturalistic set
      of stimuli and for which there are no preexisting response biases. When inverted
      faces with neutral expressions were presented alongside emotional prime and
      target faces, only strong positive priming occurred. However, when the neutral
      faces were made to resemble the target faces in geometry (upright orientation),
      time (flashing briefly), and space (appearing in the same location), positive
      priming gradually weakened and became negative priming. Implications for theories
      of the NCE are discussed.

PMID- 18087959
TI  - Cambridge University versus Hebrew University: the impact of letter transposition
      on reading English and Hebrew.
AB  - Is reading similarly affected by letter transposition in all alphabetic
      orthographies? "The Cambridge University effect", demonstrating that jumbled
      letters have little effect on reading, was examined using rapid serial visual
      presentation (RSVP) in English and in Hebrew. Hebrew-English bilinguals were
      presented sentences in both languages containing words with transposed letters.
      Sentences were presented rapidly on the screen word by word, and participants had
      to reproduce the sequence of words perceived. We found a marked difference in the
      effect of transpositions in the two languages. In English, transpositions had
      little effect on performance, whereas in Hebrew, performance deteriorated
      dramatically for words with transposed letters. The differential effects of
      transposition are accounted for by the difference in lexical organization in
      Hebrew and in English, suggesting that models of reading in alphabetic
      orthographies may be language specific.

PMID- 18087960
TI  - Nonword repetition in specific language impairment: more than a phonological
      short-term memory deficit.
AB  - The possible role of phonological short-term memory in the nonword repetition
      deficit of children with specific language impairment (SLI) was investigated in a
      study comparing serial recall and nonword repetition of sequences of auditorily
      presented CV syllables. The SLI group showed impairments in both serial recall
      and nonword repetition relative to typically developing children of the same age,
      however the SLI deficit in nonword repetition was greater and persisted even when
      differences on an independent measure of short-term memory were taken into
      account. These findings cannot be readily explained in terms of a sole deficit in
      short-term memory, and point instead to differences between the serial recall and
      nonword repetition paradigms as potential factors contributing to this disorder
      of learning.

PMID- 18087961
TI  - Language context guides memory content.
AB  - The relationship between language and memory was examined by testing
      accessibility of general knowledge across two languages in bilinguals. Mandarin
      English speakers were asked questions such as "name a statue of someone standing
      with a raised arm while looking into the distance" and were more likely to name
      the Statue of Liberty when asked in English and the Statue of Mao when asked in
      Mandarin. Multivalent information (i.e., multiple possible answers to a question)
      and bivalent information (i.e., two possible answers to a question) were more
      susceptible to language dependency than univalent information (i.e., one possible
      answer to a question). Accuracy of retrieval showed language-dependent memory
      effects in both languages, while speed of retrieval showed language-dependent
      memory effects only in bilinguals' more proficient language. These findings
      suggest that memory and language are tightly connected and that linguistic
      context at the time of learning may become integrated into memory content.

PMID- 18087963
TI  - Onset of illusory figures attenuates change blindness.
AB  - We examined whether the onset of a new object defined by illusory contours is
      detected with greater frequency than offset when neither is associated with a
      unique sensory transient. Observers performed a "one-shot" change detection task
      in which offsetting or onsetting elements of high luminance contrast circles
      generated the appearance or disappearance of a Kanizsa figure. Presenting
      "illusory figures" via this "flicker" method ensures that (1) any unique
      luminance transients associated with the two types of change are eliminated, and
      (2) the objects themselves can only be represented at a relatively high level.
      Results showed that offsets were detected more frequently than onsets only when
      they generated the onset of a Kanizsa figure. We argue that object appearance
      dominates object disappearance via mechanisms that operate at the level at which
      objects are constructed.

PMID- 18087962
TI  - The size of an attentional window modulates attentional capture by color
      singletons.
AB  - Researchers have proposed that during visual search, a color singleton cannot
      capture attention in a bottom-up fashion (Jonides & Yantis, 1988). In the present
      study, we manipulated the size of the attentional window by asking participants
      to detect either a global (diffuse attention) or a local (focused attention)
      shape before starting the search for a nonsingleton target. We demonstrate that
      increasing the size of attentional window causes the observers to frequently
      orient to an irrelevant color singleton. We conclude that although the size of
      attentional window might be under a top-down control, within the attentional
      window, an irrelevant salient singleton can capture attention in a bottom-up
      fashion.

PMID- 18087964
TI  - Phonological encoding in the attentional blink paradigm.
AB  - The attentional blink refers to a deficit in reporting a second target that
      follows a first target within a few hundred milliseconds, when both targets occur
      in a sequence of distractors shown serially at rates of about 10 items per
      second. In four experiments, phonological similarity of post-Target 1 distractors
      impaired dual target report within the interval in which the attentional blink
      occurs. Similarity of letter targets had a smaller, less reliable effect on
      performance. Phonological similarity of letter distractors did not affect single
      target identification (Experiment 3), but it continued to impair dual target
      report (Experiment 5), even when the targets belonged to a different category
      namely, digits. The results demonstrated that, not only targets, but also
      distractors are encoded phonologically, despite the fact that distractors are
      irrelevant and never have to be reported.

PMID- 18087965
TI  - Within- and between-nervous-system inhibition of return: observation is as good
      as performance.
AB  - Inhibition of return (IOR) has been shown to occur when an individual returns to
      a target location (within-person IOR) and when an individual moves to a location
      just engaged by another individual (between-person IOR). Although within- and
      between-person IOR likely result from the same inhibitory mechanisms, different
      processes must activate these mechanisms following the performance and
      observation of action. Consistent with the suggestion that the mirror neuron
      system may be responsible for activating the inhibitory mechanisms behind IOR on
      observation trials, between-person IOR was only detected under restricted viewing
      conditions known to activate mirror neurons. These results indicate that mirror
      neuron system may be involved in both higher-order and automatic cognitive
      behavior.

PMID- 18087966
TI  - Inhibition of return: unraveling a paradox.
AB  - Although inhibition of return (IOR) is widely believed to aid search by
      discouraging reexamination of previously inspected locations, its impact actually
      appears to decline as the number of target locations increases. We test three
      possible reasons for this paradoxical result: (1) IOR is capacity-limited, (2)
      IOR is sensitive to subtle changes in target location probability, and (3) IOR
      decays with distance from a previously attended location. The present
      investigation provides strong support for the third explanation, indicating that
      a gradient of inhibition is centered on previously attended locations. We note
      that this inhibitory gradient resolves a paradox in the literature. Moreover, we
      speculate that the inhibitory gradient may reflect a "similarity space" within
      which target locations near to the cue are tagged with inhibition due to their
      similarity to the cued location. The farther the target location is away, the
      less similar it is to the cued location, and thus the less inhibition it
      receives.

PMID- 18087967
TI  - Attentional control and reflexive orienting to gaze and arrow cues.
AB  - A wealth of data indicate that central spatially nonpredictive eyes and arrows
      trigger very similar reflexive spatial orienting, although the effects of eyes
      may be more strongly reflexive (e.g., Friesen, Ristic, & Kingstone, 2004). Pratt
      and Hommel (2003) recently reported that the orienting effect for arrows is
      sensitive to arbitrary cue-target color contingencies; for example, an
      attentional orienting effect for blue colored arrows is evident only for blue
      targets. We reasoned that if the orienting effect elicited by eye direction is
      more strongly reflexive than the orienting effect elicited by arrow direction, it
      follows that eyes, unlike arrows, may trigger orienting effects that generalize
      across congruent and incongruent cue-target color contingencies. Replicating
      Pratt and Hommel (2003), we found that the reflexive attention effect elicited by
      arrows is specific to color-congruent target stimuli. The attention effect
      triggered by eyes, however, generalizes across color-congruent and color
      incongruent target stimuli. These data support the hypothesis that eye direction
      and arrow direction trigger similar reflexive shifts in spatial attention, but
      that the attention effect triggered by eye direction is more strongly reflexive.

PMID- 18087968
TI  - Task-set inhibition in chunked task sequences.
AB  - Exploring the hierarchical control relationship between different levels of
      representation and processing is important for understanding how the mind
      controls itself. In the present study, the relationship between chunking (a
      sequence-level process) and task-set inhibition (a task-level process) in the
      performance of task sequences was investigated to evaluate the hypothesis that
      within-chunk facilitation reduces the n-2 repetition cost (slower performance for
      n-2 task repetitions than for n-2 task switches) attributed to task-set
      inhibition. An experiment is reported in which subjects were induced to chunk
      sequences such that n-2 repetitions occurred within or between chunks. Direct
      evidence of chunking was obtained, and n-2 repetition cost was smaller when n-2
      repetitions occurred within chunks than between chunks. These findings are
      consistent with an elaborated hypothesis that attributes the reduction in n-2
      repetition cost to priming of task goals rather than direct modulation of task
      set inhibition.

PMID- 18087969
TI  - Proactive versus reactive task-set inhibition: evidence from flanker
      compatibility effects.
AB  - Two converging tests were used to determine whether people proactively inhibit
      recently performed tasks when switching to new tasks. A task-cuing paradigm was
      used. In each trial, the relevant stimulus was accompanied by flankers belonging
      either to the task performed on the immediately preceding trial (lag 1) or a more
      distant trial (lag 2 +). If the just-performed task is inhibited when switching
      to another task, and this inhibition declines across trials, then flanker
      interference should be smaller with lag 1 flankers than with lag 2 + flankers.
      Experiment 1, following the methods of Hubner, Dreisbach, Haider, and Kluwe
      (2003), failed to confirm this prediction. The prediction was confirmed in
      Experiment 2, however, using a design modified to provide greater incentives for
      task-set inhibition. The results provide evidence that inhibition can be applied
      proactively, to reduce the ability of an abandoned task to interfere with the
      performance of other tasks.

PMID- 18087970
TI  - A Simon effect in memory retrieval: evidence for the response-discrimination
      account.
AB  - According to the traditional view, the effects of irrelevant stimulus location on
      the selection of a spatial response to a nonspatial stimulus feature (Simon
      effect) result from long-term associations between spatial stimulus codes and
      spatially corresponding response codes. According to an alternative view, the
      response-discrimination account, Simon effects arise from interactions between
      spatial stimulus codes and response labels in working memory (WM). The latter
      account predicts Simon effects when participants use spatial labels for response
      representation in WM, even when the actual responses have no spatial features
      (e.g., saying the word "plate"). The prediction was tested in an experiment, in
      which participants first encoded two words at different locations, and then
      responded to a stimulus by saying the word from the location indicated by
      stimulus color. The manipulation concerned the correspondence between irrelevant
      location of the colored stimulus and the retrieval cue for the vocal responses
      (i.e., word location in the encoding display). A Simon effect in memory retrieval
      was observed, supporting the response-discrimination account.

PMID- 18087971
TI  - Memory for moving and static images.
AB  - Despite the substantial interest in memory for complex pictorial stimuli, there
      has been virtually no research comparing memory for static scenes with that for
      their moving counterparts. We report that both monochrome and color moving images
      are better remembered than static versions of the same stimuli at retention
      intervals up to one month. When participants studied a sequence of still images,
      recognition performance was the same as that for single static images. These
      results are discussed within a theoretical framework which draws upon previous
      studies of scene memory, face recognition, and representational momentum.

PMID- 18087972
TI  - Embodiment and abstraction: actions create relational representations.
AB  - Theories of embodied, modal representation propose that concepts are grounded in
      the sensorimotor system. According to these theories, action (or the potential
      for action) creates meaning. An apparent challenge for these theories is the fact
      that higher-order relations (i.e., relations among relations), such as monotonic
      increase or alternation, have no straightforward sensorimotor analog. A single
      action can increase or alternate only relative to another action. Therefore, if
      embodied theories are to handle concepts more generally, patterns of action must
      provide meaning to the system. Previous research suggested that as participants
      simulated the motion of gear problems they discovered a higher-order relation,
      alternation, based on the episodic traces of their own alternating actions. The
      present study showed that the number of alternating actions in episodic memory
      prior to discovery of the alternation relation predicted its generalization to
      new problem types. Actions can function as the representational substrate of
      higher-order relations.

PMID- 18087973
TI  - Rotational inertia and multimodal heaviness perception.
AB  - Perceived heaviness of wielded objects has been shown to be a function of the
      objects' rotational inertia--the objects' resistance to rotational acceleration.
      Studies have also demonstrated that if virtual objects rotate faster than the
      actual wielded object (i.e., a rotational gain is applied to virtual object
      motion), the wielded object is perceived as systematically lighter. The present
      research determined whether combining those inertial and visual manipulations
      would influence heaviness perception in a manner consistent with an inertial
      model of multimodal heaviness perception. Rotational inertia and optical
      rotational gain of wielded objects were manipulated to specify inertia
      multimodally. Both visual and haptic manipulations significantly influenced
      perceived heaviness. The results suggest that rotational inertia is detected
      multimodally and that multimodal heaviness perception conforms to an inertial
      model.

PMID- 18087974
TI  - Individual differences on speeded cognitive tasks: comment on Chen, Hale, and
      Myerson (2007).
AB  - Chen, Hale, and Myerson (2007) recently reported a test of the difference engine
      model (Myerson, Hale, Zheng, Jenkins, & Widaman, 2003). This test evaluated
      whether the standard deviation (SD) is proportional to the amount of processing
      that is, mean reaction time (RT)--in a speeded cognitive task. We show that this
      evaluation is not a test of the model because its finding is a consequence of
      relationships in the data. We argue any model structure that produces increasing
      values of RT as a function of difficulty, with different slopes for different
      individuals, necessarily produces a correlation between SD and mean RT We
      illustrate this with a different model structure-that is, the diffusion model
      proposed by Ratcliff (1978)--showing that it produces a fan out between fast- and
      slow-group means and produces the correlation between SD and mean RT that matches
      the empirical result.

PMID- 18087975
TI  - Order effects in collaborative memory contamination? Comment on Gabbert, Memon,
      and Wright (2006).
AB  - Gabbert, Memon, and Wright (2006) claimed evidence of an order effect in
      collaborative memory contamination, in which the collaborator who first spoke of
      a particular detail was more influential. The Gabbert et al. findings are
      ambiguous in this regard, because their analyses collapsed across (1) cases in
      which both collaborators reported the detail they had witnessed and (2) cases in
      which only one of the collaborators mentioned the detail s/he had mentioned. The
      latter cases do not evidence an order effect per se.

PMID- 18087976
TI  - Interview with LTC Jessie L. Tucker III, Ph.D., FACHE, deputy commander for
      administration (chief operating officer), Womack Army Medical Center. Interview
      by Kyle L. Grazier.

PMID- 18087977
TI  - Applying Six Sigma and DMAIC to diversity initiatives.

PMID- 18087978
TI  - Exploring the relationship of hospital and market characteristics and organ
      donation in U.S. hospitals.
AB  - Unmet demand for organ transplantation is, in part, a result of low rates of
      organ donation. While the transplant community works diligently to improve rates
      of organ donation, patients on waiting lists for transplantation continue to die.
      This article reviews factors that are associated with rates of organ donation at
      U.S. hospitals. We analyzed two years of data on the numbers of actual and
      potential donors at U.S. hospitals to discern whether hospital or market
      attributes are directly related to a hospital's rate of securing organ donations.
      We found that certain hospital characteristics are related to higher donation
      rates. Further research and a deeper understanding of organizational and
      environmental influences on the complex nature of securing organ donations are
      needed to help alleviate transplantation waiting lists.

PMID- 18087979
TI  - Nurse residency program implementation: the Utah experience.
AB  - Recently, nurse residency programs have been shown to improve satisfaction and
      enhance the retention of new graduate nurses, offering one solution for hospital
      executives, administrators, and managers searching for innovative ways to address
      nursing staff shortages. This article identifies crucial lessons that will assist
      leaders in designing and implementing a nurse residency program in their own
      institutions. The lessons are drawn from the experience of the successful
      University of Utah program. Four important practical components of such programs
      are described: an adaptive curriculum, promotion of autonomy, mentoring, and
      meeting the needs of participants with associate degrees. Although the lessons
      are based on the perspective of one nurse residency program, they hold import for
      the design of nurse residency programs in diverse settings.

PMID- 18087980
TI  - Hospital adoption of information technologies and improved patient safety: a
      study of 98 hospitals in Florida.
AB  - Most of the studies linking the use of information technology (IT) to improved
      patient safety have been conducted in academic medical centers or have focused on
      a single institution or IT application. Our study explored the relationship
      between overall IT adoption and patient safety performance across hospitals in
      Florida. Primary data on hospital IT adoption were combined with secondary
      hospital discharge data. Regression analyses were used to examine the
      relationship between measures of IT adoption and the Patient Safety Indicators
      (PSIs) of the Agency for Healthcare Research and Quality. We found that eight
      PSIs were related to at least one measure of IT adoption. Compared with
      administrative IT adoption, clinical IT adoption was related to more patient
      safety outcome measures. Hospitals with the most sophisticated and mature IT
      infrastructures performed significantly better on the largest number of PSIs.
      Adoption of IT is associated with desirable performance on many important
      measures of hospital patient safety. Hospital leaders and other decision makers
      who are examining IT systems should consider the impact of IT on patient safety.

PMID- 18087982
TI  - Early diagnosis is key to curing melanoma.

PMID- 18087981
TI  - Financial preconditions for successful community initiatives for the uninsured.
AB  - Community-based initiatives are increasingly being implemented as a strategy to
      address the health needs of the community, with a growing body of evidence on
      successes of various initiatives. This study addresses financial status
      indicators (preconditions) that might predict where community-based initiatives
      might have a better chance for success. We evaluated five community-based
      initiatives funded by the Communities in Charge (CIC) program sponsored by the
      Robert Wood Johnson Foundation. These initiatives focus on increasing access by
      easing financial barriers to care for the uninsured. At each site, we collected
      information on financial status indicators and interviewed key personnel from
      health services delivery and financing organizations. With full acknowledgment of
      the caveats associated with generalizations based on a small number of
      observations, we suggest four financial preconditions associated with successful
      initiation of CIC programs: (1) uncompensated care levels that negatively affect
      profitability, (2) reasonable financial stability of providers, (3) stable health
      insurance market, and (4) the potential to create new sources of funding. In
      general, sites that demonstrate successful program initiation are financially
      stressed enough by uncompensated care to gain the attention of local healthcare
      providers. However, they are not so strained and so concerned about revenue
      sources that they cannot afford to participate in the initiative. In addition to
      political and managerial indicators, we suggest that planning for community-based
      initiatives should include financial indicators of current health services
      delivery and financing organizations and consideration of whether they meet
      preconditions for success.

PMID- 18087983
TI  - New developments in the treatment of asthma.

PMID- 18087984
TI  - Have a high index of suspicion for TB.

PMID- 18087985
TI  - Managing adults with cystic fibrosis.

PMID- 18087986
TI  - "Weak hearts" in general practice. 1907.

PMID- 18087987
TI  - Helping patients to overcome obsessive compulsive disorder.

PMID- 18087988
TI  - Iatrogenic conditions.

PMID- 18087989
TI  - Four-year cost-utility analyses of sealed and nonsealed first permanent molars in
      Iowa Medicaid-enrolled children.
AB  - OBJECTIVES: Dental sealants, by their ability to prevent caries and maintain
      teeth in better health, have some inherent utility to individuals, programs, or
      society. This study assessed the 4-year incremental cost utility of sealing first
      permanent molars of 6-year-old Iowa Medicaid enrollees from a societal
      perspective and identified the group of teeth or children in whom sealants are
      most cost effective. METHODS: Dental services for first permanent molars were
      assessed using claims and encounter data for a group of continuously enrolled
      Medicaid enrollees who turned 6 between 1996 and 1999. Previously published
      utilities were used to weight the different health states. The weighted sum of
      outcomes [Quality-Adjusted Tooth-Years (QATYs)] was the measure of effectiveness.
      Costs and QATYs were discounted to the time of the child's sixth birthday.
      RESULTS: For all first molars, the cost of treatment associated with sealed teeth
      was higher but the utility was also slightly higher over the 4-year period. The
      relative incremental cost per 0.19 QATY ratio [changing the health state from a
      restored tooth (utility= 0.81) to a nonrestored tooth (utility = 1)] by sealing
      the molar ranged from $36.7 to $83.5 per 0.19 QATY. The incremental cost/QATY
      ratio was lower for sealing lower utilizers and for mandibular versus maxillary
      molars. CONCLUSIONS: Sealants improved overall utility of first permanent molars
      after 4 years. The 4-year cost/QATY ratio of sealing the first permanent molar
      varied by arch and type of utilizers. Sealing first permanent molars in lower
      dental utilizers is the most cost-effective approach for prioritizing limited
      resources.

PMID- 18087990
TI  - Characteristics of publicly insured children with high dental expenses.
AB  - BACKGROUND: Dental coverage is provided for all children with Medicaid in
      Washington State. The goal of this study was to illuminate the characteristics of
      a sample of Medicaid-enrolled children with high dental expenses. METHODS: Dental
      care utilization data for a 33-month period were obtained from Washington State's
      Medicaid database. For children, 0 to 6 years, these data were linked with a
      parent survey addressing oral health behaviors, knowledge, family history of
      caries, snacking patterns, and access to dental care. Children with dental
      expenses of $1,000 or more were classified as the "high-expense" group. Risk
      factors for the high-expense group were evaluated using multiple logistic
      regression. RESULTS: 345 children had at least one dental procedure including
      preventive and diagnostic care. Among these, 30 children (9 percent) incurred 64
      percent of total dental expenses for the entire group. Parent perception of lack
      of dental coverage was associated with incurring high dental expenses. Children
      of Asian or Pacific Islander heritage were at disproportionately high risk
      compared to White children. Age of child and family history of caries were also
      associated with increased risk for high expenses. CONCLUSIONS: Not all low-income
      children on Medicaid are at high risk for caries. A combination of factors,
      including family history of caries and parent's perception of lack of dental
      insurance coverage, can potentially increase a child's likelihood for high
      expense dental treatment. This study highlighted a small group of children with
      disproportionately high dental expenses. For some, earlier knowledge of coverage
      may have resulted in more timely access to preventive and diagnostic care,
      reducing the subsequent need for expensive restorative treatment.

PMID- 18087991
TI  - Characteristics of dentists providing dental care to publicly insured patients.
AB  - OBJECTIVE: This study aims to identify the practice and patient care
      characteristics of dentists who provide care to publicly insured patients, beyond
      currently available existing information, which is typically limited to
      demographics of such dentists. METHODS: A cross-section of dentists in private
      practices in California was surveyed, with a 46 percent average adjusted response
      rate. The sample included 3,180 generalists or specialists who provided general
      care in private practice. Characteristics of dentists who provided care to
      publicly insured patients were examined in descriptive analyses. The independent
      association of dentist characteristics with the provision of any care and the
      provision of care to a significant number of publicly insured patients were
      examined in logistic regression analyses. RESULTS: Over 40 percent of dentists
      saw public patients. Regression analyses revealed that dentists who spent more
      time in periodontic and surgical care, saw more walk-in patients, had
      multilingual capacity, accepted reduced fees, had more minority patients, had
      fewer hygienists, or had multiple practice locations were more likely than those
      without such characteristics to provide care to publicly insured patients.
      CONCLUSIONS: Dentists who care for publicly insured patients appear to have
      practices that are different from those who do not, in terms of delivery of
      patient care and practice structure. Such differences have implications for the
      access to and quality of dental health care of publicly insured patients. The
      success of public programs and policies aimed at ensuring access to dental care
      depends on ability and willingness of dentists to accommodate public patients'
      needs.

PMID- 18087992
TI  - Racial/ethnic disparities in self-reported pediatric orthodontic visits in the
      United States.
AB  - OBJECTIVE: Studies in orthodontics have focused primarily on clinical care and
      techniques. Little, however, has been reported from epidemiological studies using
      national data on orthodontic dental visits as a measure of orthodontic service
      utilization and access to care in minority populations. We examined the effect of
      race/ethnicity and socioeconomic factors on pediatric orthodontic visits in the
      United States. METHODS: We analyzed data from the Medical Expenditure Panel
      Survey, 1996-2004. Descriptive and multiple regression analyses were performed,
      with self-reported orthodontic visits in a given year as the main outcome
      variable. RESULTS: The prevalence of an orthodontic visit among children ages 9
      to 18 years remained relatively constant (ranged between 14.3 percent and 16.8
      percent) from 1996 to 2004. Multiple regression analyses revealed significantly
      lower odds of an orthodontic visit for Black and Hispanic children in comparison
      with White children. Males, children from low-income families, children eligible
      for Medicaid, and children with other public or no insurance were generally less
      likely to have made an orthodontic visit. CONCLUSION: Substantial racial/ethnic
      disparities in self-reported orthodontic visits exist for Black and Hispanic
      children even after adjusting for possible covariates. Children from lower-income
      families and those without private health insurance were less likely to report an
      orthodontic visit in the United States.

PMID- 18087993
TI  - A comparison of dental treatment utilization and costs by HMO members living in
      fluoridated and nonfluoridated areas.
AB  - OBJECTIVES: To compare dental treatment experiences and costs in members of a
      health maintenance organization (HMO) in areas with and without community water
      fluoridation. METHODS: HMO members with continuous dental eligibility (January 1,
      1990 to December 31, 1995) who resided in Oregon and Washington were identified
      using administrative databases. Fluoridation status was determined by geocoding
      subscriber address. Measures were utilization of dental procedures, fluoride
      dispensings, and associated costs. Costs were based on nonmember fees, adjusted
      to 1995 dollar values. Data were analyzed using analysis of covariance,
      controlling for age and interactions. RESULTS: About 85 percent of eligible
      members (n = 51,683) were classified as residing either in a fluoridated (n =
      12,194) or nonfluoridated (n = 39,489) area. Mean age was 40.0 years; 52.3
      percent were women. More than 92 percent of members had one or more dental
      visits. Community water fluoridation was associated with reduced total and
      restorative costs among members with one or more visits, but the magnitude and
      direction of the effect varied with locale and age and the effects were generally
      small. In two locales, the cost of restorations was higher in nonfluoridated
      areas in young people (<age 18) and older adults (>age 58). In younger adults,
      the opposite effect was observed. The impact of fluoridation may be attenuated by
      higher use of preventive procedures, in particular supplemental fluorides, in the
      nonfluoridated areas. CONCLUSIONS: These results are particularly relevant to
      insured populations with established access to dental care. Differences in
      treatment costs (savings) associated with water fluoridation should be estimated
      and included in future cost-effectiveness analyses of community water
      fluoridation.

PMID- 18087994
TI  - Household expenditure in dental health care: national estimations in Mexico for
      2000, 2002, and 2004.
AB  - OBJECTIVE: To estimate the expenditure on dental care of Mexican households,
      analyze their trends, and determine the factors associated with the decision to
      spend and the amount of money spent in 2000, 2002, and 2004. MATERIAL AND
      METHODS: Using the National Survey of Household Income and Expenditure for 2000,
      2002, and 2004, the national dental health care expenditure was calculated. To
      facilitate comparability across years, all expenditure was converted to pesos of
      2004, using the National Consumer Price Index (11.201 pesos per USD). Proportion
      of households incurring catastrophic expenditures was also estimated. To evaluate
      the association between environmental, household, and individual characteristics
      with the amount of dental health care expenditure, the Heckman regression model
      was used to control for self-selection bias. RESULTS: More than 6,467 million
      pesos (MP) were spent in 2000 (8.5 percent of all households had some
      expenditure), over 3,925 MP in 2002 (4 percent households), and above 5,136 MP in
      2004 (5 percent households), with an average expenditure of $806, $1,000, and
      $987 pesos, respectively. Prevalence of catastrophic expenditure because of
      dental health care was 0.8 percent in 2000 compared to 0.01 and 1.8 percent in
      2002 and 2004, respectively. The Heckman model showed that municipal development,
      stratum, and age of the head of household significantly influenced the amount
      spent on dental care in all 3 years. Household capacity to pay and wealth index
      had a positive and statistically significant association in the 3 years with the
      preceding decision to spend. CONCLUSIONS: Variables associated with the amount of
      expenditure and the decision of spending support the existence of inequities in
      health care financing in the Mexican population.

PMID- 18087995
TI  - Risk indicators for missing teeth in working-age Pomeranians--an evaluation of
      high-risk populations.
AB  - OBJECTIVE: The goal of this study was to examine whether psychosocial conditions
      for general health described in the public health literature are also reflected
      in tooth loss. METHODS: The relation of psychosocial factors to missing teeth was
      evaluated among 2,501 individuals aged 25 to 59 years from the population-based
      cross-sectional Study of Health in Pomerania using logistic regression analyses.
      The case group included 15 percent of participants of each 5-year age group with
      the highest number of missing teeth. RESULTS: Unemployment, dose-dependent
      current and former smoking, a poor general health status, and a longer time since
      the last dental appointment were significant risk indicators for missing teeth.
      Alcohol consumption, use of interdental cleaning products, and checkup as the
      reason for the last dental visit were protective. Women with low education and
      low income were identified as a high-risk group for missing teeth by the three
      way interaction between gender, school education, and household income. The
      effect of marital status was modified by gender: being single was a risk
      indicator for men but it was protective for women. CONCLUSIONS: The study
      supports the hypothesis that psychosocial conditions that affect health status as
      described in the general public health literature also have an effect on tooth
      loss. Strategies to prevent tooth loss may be expeditiously implemented in
      combination with approaches to prevent other health-related problems.

PMID- 18087996
TI  - Assessing the viability of the independent practice of dental hygiene--a brief
      communication.
AB  - BACKGROUND: This paper deals with the economics of the independent dental hygiene
      practice. METHODS: Using historical data from dental practices in Cincinnati,
      Ohio, we developed a business model for an independent hygiene practice. We
      tested the sensitivity of the model to variations in key assumptions (initial
      capitalization, interest, employee salary, and owner's draw). We described the
      profitability on the basis of the breakeven point. RESULTS: Under the most
      permissive regulatory and financial environment, the practice would breakeven
      after 26 months. However, the owner would not equal the earnings of a salaried
      hygienist until the initial loan is paid off after 7 years. The model was not
      sensitive to 20 percent changes in the key assumptions. CONCLUSIONS: Under ideal
      circumstances, an independent hygiene practice could be profitable.

PMID- 18087997
TI  - The effects of cell density and device arrangement on the behavior of
      macroencapsulated beta-cells.
AB  - Over the last several decades, considerable research has focused on the
      development of cell encapsulation technology to treat a number of diseases,
      especially type 1 diabetes. One of the key advantages of cell encapsulation is
      that it permits the use of xenogenic tissue, particularly animal-derived cell
      lines. This is an attractive idea, because it circumvents the issue of a limited
      human organ supply. Furthermore, as opposed to whole islets, cell lines have a
      better proliferative capacity and can easily be amplified in culture to provide
      an endless supply of uniform cells. We have previously described a
      macroencapsulation device for the immunoisolation of insulin-secreting 1-cells.
      The aim of this work was to optimize the viability and insulin secretion of cells
      encapsulated within this device. Specifically, the effects of cell packing
      density and device membrane configuration were investigated. The results
      indicated that cell density plays an important role in the secretory capacity of
      the cells, with higher cell density leading to increased insulin secretion.
      Increasing the transport area of the capsule by modifying the membrane
      configuration also led to an improvement in the insulin output of the device.

PMID- 18087998
TI  - Expression of transforming growth factor-beta by human islets: impact on islet
      viability and function.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a pleotropic cytokine that
      promotes angiogenesis and extracellular matrix protein synthesis in addition to
      its immunosuppressive effects. The purpose of this study is to identify optimal
      conditions for in vivo expression of TGF-beta1 by human islets to exploit the
      possible beneficial effects and minimize undesirable side effects. We transduced
      human islets with adenoviral vectors encoding the active form of Ad-TGF-beta1 or
      Ad-LacZ to test the effects of TGF-beta1 gene expression on islet in vivo
      function following their transplantation into a NOD-SCID mouse model. Islets were
      transduced with multiplicity of infection (MOI) of 20, 10, 5, and 2.5 per islet
      cell. At a MOI ranging from 2.5 to 20, expression of TGF-beta1 in islet
      supernatant persisted for 1-2 months and ranged from 153 +/- 5 to 2574 +/- 1299
      pg/ml, respectively. Transduction with the lowest MOI (2.5) did not compromise
      the in vivo production of human C-peptide. We conclude that TGF-beta1 expression
      in transplanted islets does not compromise viability and that adenoviral
      transduction with the TGF-beta1 gene has a dose-dependent effect, with larger
      MOIs being deleterious. The data also indicate that in vitro culture system and
      the in vivo NOD-SCID model could be used successfully to evaluate the nonimmune
      effects of gene transduction.

PMID- 18087999
TI  - Combination of anti-CD4 with anti-LFA-1 and anti-CD154 monoclonal antibodies
      promotes long-term survival and function of neonatal porcine islet xenografts in
      spontaneously diabetic NOD mice.
AB  - Type 1 diabetes mellitus (T1DM) is caused by the autoimmune destruction of
      pancreatic islet beta-cells, which are required for the production of insulin.
      Islet transplantation has been shown to be an effective treatment option for
      TIDM; however, the current shortage of human islet donors limits the application
      of this treatment to patients with brittle T1DM. Xenotransplantation of pig
      islets is a potential solution to the shortage of human donor islets provided
      xenograft rejection is prevented. We demonstrated that a short-term
      administration of a combination of anti-LFA-1 and anti-CD154 monoclonal
      antibodies (mAbs) was highly effective in preventing rejection of neonatal
      porcine islet (NPI) xenografts in non-autoimmune-prone B6 mice. However, the
      efficacy of this therapy in preventing rejection of NPI xenografts in autoimmune
      prone nonobese diabetic (NOD) mice is not known. Given that the current
      application of islet transplantation is for the treatment of T1DM, we set out to
      determine whether a combination of anti-LFA-1 and anti-CD154 mAbs could promote
      long-term survival of NPI xenografts in NOD mice. Short-term administration of a
      combination of anti-LFA-1 and anti-CD154 mAbs, which we found highly effective in
      preventing rejection of NPI xenografts in B6 mice, failed to promote long-term
      survival of NPI xenografts in NOD mice. However, addition of anti-CD4 mAb to
      short-term treatment of a combination of anti-LFA-1 and anti-CD154 mAbs resulted
      in xenograft function in 9/12 animals and long-term graft (>100 days) survival in
      2/12 mice. Immunohistochemical analysis of islet grafts from these mice
      identified numerous insulin-producing beta-cells. Moreover, the anti-porcine
      antibody as well as autoreactive antibody responses in these mice was reduced
      similar to those observed in naive nontransplanted mice. These data demonstrate
      that simultaneous targeting of LFA-1, CD154, and CD4 molecules can be effective
      in inducing long-term islet xenograft survival and function in autoimmune-prone
      NOD mice.

PMID- 18088000
TI  - Neural progenitor cells derived from the adult rat subventricular zone:
      characterization and transplantation.
AB  - In order to fully characterize and determine the therapeutic potential of adult
      neural progenitor cells (NPCs), it is important to be able to isolate and study
      NPCs from animals such as rats, in which there are existing models of brain
      injury and disease. The focus of this study was to characterize the cultivation,
      differentiation, and transplantation of adult rat NPCs isolated from the
      subventricular zone of the lateral ventricles. We examined strategies for cell
      purification using a Percoll density gradient, and cell expansion using a range
      of maintenance medium and plating densities. Purification by Percoll gradient
      enriched a population of cells expressing nestin and SOX2, but resulted in a
      significant reduction in neurosphere generation. Culturing adult rat NPCs in
      Neurobasal-A media and plating at 200,000 cell/ml resulted in a higher percentage
      of cells surviving to generate neurospheres compared to culture in DMEM/F12 or NS
      A media. On induction of differentiation, adult rat NPCs were capable of
      generating neurons, astrocytes, and oligodendrocytes in vitro that survived for
      up to 8 weeks, demonstrating multipotentiality of these cells. In addition, a
      population of cells continued to proliferate during the initial phase of
      differentiation, suggesting the presence of two populations of NPCs during
      differentiation. Cultured adult rat NPCs also survived and differentiated into
      astrocytes 6 weeks after transplantation into the striatum of the normal adult
      rat brain. In conclusion, we have optimized techniques that allow for the routine
      isolation, culture, and transplantation of multipotent NPCs derived from the
      adult rat SVZ.

PMID- 18088001
TI  - Nerve regeneration promoted in a tube with vascularity containing bone marrow
      derived cells.
AB  - Bone marrow-derived cells (BMCs) are multipotent cells that have the potential to
      differentiate into bone, cartilage, fat, muscle, or neuronal lineages such as
      neurons and glial cells. A silicone tube model containing reverse-pedicled sural
      vessels was created in the sciatic nerves of Lewis rats. About 1 x 10(7) BMCs,
      removed from the bone marrow of synergetic rat femurs and cultured in vitro, were
      transplanted into the 15-mm-long chambers of the silicone tubes. Nerve
      regeneration in vessel-containing tubes that had received BMCs was significantly
      greater at 12 and 24 weeks after surgery than in tubes that did not receive
      cells. Transplantation of fibroblasts instead of BMCs into the vessel-containing
      tube resulted in reduced axonal regeneration, which was inferior to regeneration
      in the vessel-containing tube that did not receive cells. Polymerase chain
      reaction (PCR) studies revealed that in vessel-containing tubes containing
      transplanted BMCs, about 29% of cells in the regenerated nerve originated from
      BMCs. Cells identified by in situ hybridization and PKH26 prelabeling as being of
      BMC origin stained positively for S100 and GFAP. Transplanted BMCs differentiated
      into cells with phenotypes similar to those of Schwann cells under the influence
      of neurochemical factors and survived by obtaining nutrients from vessels that
      had been preinserted into the tube. They thus functioned similarly to Schwann
      cells, promoting nerve regeneration.

PMID- 18088002
TI  - Comparison of chondral defects repair with in vitro and in vivo differentiated
      mesenchymal stem cells.
AB  - The purpose of this study was to compare chondral defects repair with in vitro
      and in vivo differentiated mesenchymal stem cells (MSCs). A novel PLGA
      gelatin/chondroitin/hyaluronate (PLGA-GCH) hybrid scaffold with transforming
      growth factor-beta1 (TGF-beta1)-impregnated microspheres (MS-TGF) was fabricated
      to mimic the extracellular matrix. MS-TGF showed an initial burst release (22.5%)
      and a subsequent moderate one that achieved 85.1% on day 21. MSCs seeded on PLGA
      GCH/MS-TGF or PLGA-GCH were incubated in vitro and showed that PLGA-GCH/MS-TGF
      significantly augmented proliferation of MSCs and glycosaminoglycan synthesis
      compared with PLGA-GCH. Then MSCs seeded on PLGA-GCH/MS-TGF were implanted and
      differentiated in vivo to repair chondral defect on the right knee of rabbit (in
      vivo differentiation repair group), while the contralateral defect was repaired
      with in vitro differentiated MSCs seeded on PLGA-GCH (in vitro differentiation
      repair group). The histology observation demonstrated that in vivo
      differentiation repair showed better chondrocyte morphology, integration, and
      subchondral bone formation compared with in vitro differentiation repair 12 and
      24 weeks postoperatively, although there was no significant difference after 6
      weeks. The histology grading score comparison also demonstrated the same results.
      The present study implies that in vivo differentiation induced by PLGA-GCH/MS-TGF
      and the host microenviroment could keep chondral phenotype and enhance repair. It
      might serve as another way to induce and expand seed cells in cartilage tissue
      engineering.

PMID- 18088003
TI  - Subcultured odontogenic epithelial cells in combination with dental mesenchymal
      cells produce enamel-dentin-like complex structures.
AB  - We showed in a previous study that odontogenic epithelial cells can be
      selectively cultured from the enamel organ in serum-free medium and expanded
      using feeder layers of 3T3-J2 cells. The subcultured odontogenic epithelial cells
      retain the capacity for ameloblast-related gene expression, as shown by
      semiquantitative RT-PCR. The purpose of the present study was to evaluate the
      potential of subcultured odontogenic epithelial cells to form tooth structures in
      cell-polymer constructs maintained in vivo. Enamel organs from 6-month-old
      porcine third molars were dissociated into single odontogenic epithelial cells
      and subcultured on feeder layers of 3T3-J2 cells. Amelogenin expression was
      detected in the subcultured odontogenic epithelial cells by immunostaining and
      Western blotting. The subcultured odontogenic epithelial cells were seeded onto
      collagen sponge scaffolds in combination with fresh dental mesenchymal cells, and
      transplanted into athymic rats. After 4 weeks, enamel-dentin-like complex
      structures were present in the implanted constructs. These results show that our
      culture system produced differentiating ameloblast-like cells that were able to
      secrete amelogenin proteins and form enamel-like tissues in vivo. This
      application of the subculturing technique provides a foundation for further tooth
      tissue engineering and for improving our understanding of ameloblast biology.

PMID- 18088005
TI  - Isolation of mouse hepatocytes for transplantation: a comparison between
      antegrade and retrograde liver perfusion.
AB  - We compared antegrade with retrograde liver perfusion when isolating mouse
      hepatocytes for hepatocyte transplantation. Male mouse hepatocytes were isolated
      by different perfusion methods and transplanted into the spleen of congeneic
      female mice. Retrograde perfusion yielded a larger number of cells (4.90 x 10(7))
      than antegrade (4.09 x 10(7), p < 0.05), but hepatocytes obtained by antegrade
      perfusion gave higher engraftment efficiency (p < 0.05). More of the transplanted
      hepatocytes could be recovered from recipient liver with antegrade perfusion than
      with retrograde perfusion (p < 0.05). Our results indicate that hepatocytes
      isolated by antegrade perfusion gave a higher engraftment efficiency.

PMID- 18088004
TI  - Efficient intracytoplasmic labeling of human umbilical cord blood mesenchymal
      stromal cells with ferumoxides.
AB  - Mesenchymal stromal cells (MSCs) are multipotent cells found in several adult
      tissues; they have the capacity to differentiate into mesodermal, ectodermal, and
      endodermal tissues in vitro. There have been several reports that MSCs have
      therapeutic effects in a variety of diseases. Therefore, using a cell labeling
      technique, monitoring their temporal and spatial migration in vivo, would be
      useful in the clinical setting. Magnetic resonance imaging (MRI)--tracking of
      superparamagnetic iron oxide (SPIO)-labeled cells--is a noninvasive technique for
      determining the location and migration of transplanted cells. In the present
      study, we evaluated the influence and toxicity of SPIO (ferumoxides) labeling on
      multiple differentiated MSCs. To evaluate the influence and toxicity of
      ferumoxides labeling on differentiation of MSCs, a variety of concentrations of
      ferumoxides were used for labeling MSCs. We found that the cytoplasm of adherent
      cells was effectively labeled at low concentrations of ferumoxides. Compared with
      unlabeled controls, the ferumoxides-labeled MSCs exhibited a similar
      proliferation rate and apoptotic progression. The labeled MSCs differentiated
      into osteoblasts and adipocytes in an identical fashion as the unlabeled cells.
      However, chondrogenesis and neurogenesis were inhibited at high concentrations of
      ferumoxides. Our results suggest the effective concentration for ferumoxides use
      in tracking MSCs.

PMID- 18088006
TI  - Stem cell research in Cell Transplantation: an analysis of geopolitical influence
      by publications.
AB  - One of the fastest growing fields in researching treatments for neurodegenerative
      and other disorders is the use of stem cells. These cells are naturally occurring
      and can be obtained from three different stages of an organism's life: embryonic,
      fetal, and adult. In the US, political doctrine has restricted use of federal
      funds for stem cells, enhancing research towards an adult source. In order to
      determine how this legislation may be represented by the stem cell field, a
      retrospective analysis of stem cell articles published in the journal Cell
      Transplantation over a 2-year period was performed. Cell Transplantation is
      considered a translational journal from preclinical to clinical, so it was of
      interest to determine the publication outcome of stem cell articles 6 years after
      the US regulations. The distribution of the source of stem cells was found to be
      biased towards the adult stage, but relatively similar over the embryonic and
      fetal stages. The fetal stem cell reports were primarily neural in origin,
      whereas the adult stem cell ones were predominantly mesenchymal and used mainly
      in neural studies. The majority of stem cell studies published in Cell
      Transplantation were found to fall under the umbrella of neuroscience research.
      American scientists published the most articles using stem cells with a bias
      towards adult stem cells, supporting the effect of the legislation, whereas
      Europe was the leading continent with a bias towards embryonic and fetal stem
      cells, where research is "controlled" but not restricted. Japan was also a major
      player in the use of stem cells. Allogeneic transplants (where donor and
      recipient are the same species) were the most common transplants recorded,
      although the transplantation of human-derived stem cells into rodents was the
      most common specific transplantation performed. This demonstrates that the use of
      stem cells is an increasingly important field (with a doubling of papers between
      2005 and 2006), which is likely to develop into a major therapeutic area over the
      next few decades and that funding restrictions can affect the type of research
      being performed.

PMID- 18088007
TI  - Mycobacterium bovis BCG induces high mobility group box 1 protein release from
      monocytic cells.
AB  - High mobility group box 1 protein (HMGB-1), a nuclear protein is a critical
      cytokine that mediates the response to infection, injury and inflammation. The
      aim of our study was to elaborate a reliable in vitro model to investigate
      whether Mycobacterium bovis BCG is able to induce HMGB-1 secretion from the
      monocytic U-937 cells. Western blot technique was applied for the detection of
      HMGB-1 from supernatants of cells, following induction with LPS, Staphylococcus
      aureus, and Mycobacterium bovis BCG. HMGB-1 was subjected to MALDI-TOF mass and
      PSD analysis. Quantitation of the secreted HMGB-1 was performed by ELISA. The BCG
      strain induced higher amounts of secreted HMGB-1 than LPS or Staphylococcus
      aureus. The translocation of the HMGB-1 to the cytoplasm following infection of
      cells with BCG was demonstrated by immunofluorescence examinations. CONCLUSION:
      Our pilot experiments draw attention the to HMGB-1-inducing ability of
      Mycobacterium bovis. Assessment of the pathophysiological role of this late
      cytokine in mycobacterial infections demands further in vitro and in vivo
      examinations.

PMID- 18088008
TI  - Diversity of reed (Phragmites australis) stem biofilm bacterial communities in
      two Hungarian soda lakes.
AB  - From reed biofilm samples of Kelemen-szek (Kiskunsag National Park, KNP) and Nagy
      Vadas (Hortobagy National Park, HNP) altogether 260 bacterial isolates were
      gained after serial dilutions and plating onto different media. Following a
      primary selection 164 strains were investigated by "traditional" phenotypic tests
      and clustered by numerical analysis. Fifty-six representative strains were
      selected to ARDRA and 16S rDNA sequence analysis for identification. Strains were
      identified as members of genera Agrobacterium, Paracoccus, Halomonas,
      Pseudomonas, Bacillus, Planococcus and Nesterenkonia. The species diversity was
      also investigated by a cultivation independent method. A clone library was
      constructed using the community DNA isolated from the biofilm sample of Kelemen
      szek. Screening of the 140 bacterial clones resulted in 45 different ARDRA
      groups. Sequence analysis of the representatives revealed a great phylogenetic
      diversity. A considerable majority of the clones was affiliated with uncultured
      bacterial clones (with sequence similarity between 93 and 99%) originating from
      diverse environmental samples (for example salt marshes, compost or wastewater
      treatment plants). The DNA sequences of other clones showed the presence of
      genera Flavobacterium, Sphingobacterium, Pseudomonas and Agrobacterium.

PMID- 18088009
TI  - Antimicrobial effects of Piper guineense 'Uziza' and Phyllantus amarus 'Ebe
      benizo' on Candida albicans and Streptococcus faecalis.
AB  - Two pathogens were employed, Streptococcus faecalis and Candida albicans for the
      study of the antimicrobial effects of Piper guineense and Phyllantus amarus using
      agar-well diffusion and disc-diffusion methods. Phytochemical screening of
      ethanol, cold and hot water extracts detected the presence of tannins, saponins,
      flavonoids, terpenoids and phlobatannins. Antimicrobial effect of the plant
      extracts showed that the organic solvent and aqueous solvents of P. amarus were
      inhibitory to S. faecalis while the extracts of Phyllantus amarus were not
      inhibitory to Candida albicans. Agar-well determined Minimum Inhibitory
      Concentration (MIC) values ranged between 3.125 mg/ml and 6.25 mg/ml while the
      disc diffusion determined MIC values ranged between 6.25 mg/ml and 25.0 mg/ml.
      The agar-well determined MIC values for the ethanolic P. amarus extracts (3.12
      mg/ml) were lower than the corresponding disc-diffusion MIC determined values
      (6.25 mg/ml-25.00 mg/ml). Bacteriocidal and bacteriostatic effect varied with,
      solvent type of extract, concentration of the plant extract and the method of the
      test adopted. The active components of the plant have no antifungal effect on the
      tested yeast (Candida albicans). These findings are discussed in relation to
      plant chemicals as a means of disease control and also to the problem of
      microbial resistance to synthetic drugs.

PMID- 18088010
TI  - Membrane fluidity and lipid composition in clinical isolates of Candida albicans
      isolated from AIDS/HIV patients.
AB  - In this study, we describe the membrane lipid composition of eight clinical
      isolates (azole resistant and sensitive strains) of Candida albicans isolated
      from AIDS/ HIV patients. Interestingly, fluorescence polarization measurements of
      the clinical isolates displayed enhanced membrane fluidity in fluconazole
      resistant strains as compared to the sensitive ones. The increase in fluidity was
      reflected in the change of membrane order, which was considerably decreased
      (decrease in fluorescence polarization "p" value denotes higher membrane
      fluidity) in the resistant strains. The ergosterol content in azole susceptible
      isolates was greater, almost twice as compared to the resistant isolates.
      However, no significant alteration was observed in phospholipid and fatty acid
      composition of these isolates. Labeling experiments with fluorescamine dye
      revealed that the percentage of phosphatidylethanolamine exposed to the
      membrane's outer leaflet was higher in the resistant strains as compared to the
      sensitive strains, indicating increased floppase activity of the two major ABC
      drug efflux pumps, CDR1 and CDR2 possibly due to their overexpression in
      resistant strains. The results of the present study suggest that changes in the
      status of membrane lipid phase especially the ergosterol content and increased
      activity of drug efflux pumps by overexpression ofABC transporters, CDR1 and CDR2
      might contribute to fluconazole resistance in C. albicans isolated from AIDS/HIV
      patients.

PMID- 18088011
TI  - Conjugation potential and class 1 integron carriage of resident plasmids in river
      water copiotrophs.
AB  - Plasmid content was investigated in hundred copiotrophic Gram-negative river
      water isolates that exhibited resistance to four or more antibiotics. A total of
      seventy-seven isolates were found to carry plasmids of varying sizes. These
      isolates were primarily grouped as Pseudomonads and members of Enterobacteriaceae
      on the basis of physiological and biochemical tests. Fifty-six isolates that were
      rifampicin-sensitive and belonged to Enterobacteriaceae family were chosen as
      donors for the conjugal transfer assay. Eighteen of the isolates successfully
      transferred conjugable plasmids to the E. coli DH5alpha recipient. Countable
      multiple antibiotic resistant transconjugants arose readily and conjugal transfer
      frequency was in the range of 3.75 x 10(-6) to 1.0 x 10(-1). The most common
      carriage of resistances conferred by transmissible R plasmids was against
      ampicillin, cefotaxim and cephalexin. The residence of class 1 integrons on
      conjugative R plasmids was confirmed in only six transconjugants. Gene cassettes
      borne on the integrons were identified to be dihydrofolate reductases (dhfrs).
      The major concern of this study was about the copiotrophs containing self
      transmissible R plasmids which may be potential reservoirs of antibiotic
      resistance genes and instrumental in dissemination of the same in the
      environment.

PMID- 18088012
TI  - The effect of salt concentration and pH on the heat resistance of Escherichia
      coli in tryptic soy broth.
AB  - The effect of the acid and the osmotic stress on the heat resistance of
      Escherichia coli (EC1 and EC2) was studied at 63 degrees C in tryptic soy broth
      adjusted to various pHs (2.5, 4.5 and 6) and various NaCl concentrations (2, 4
      and 8%). In the second study, the effect of pretreatment on thermotolerance of E.
      coli cells was determined. The heat resistance of both strains was low at pH 2.5,
      but strain EC1 was more resistant than strain EC2. On the contrary, the heat
      resistance increased with increasing the pH values. Addition of NaCl (2%) to TSB
      medium, was involved in the protection of cells against heat inactivation, this
      protective effect was, however, not observed by increasing the NaCl concentration
      up to 8%. The combined effect of the pH and NaCl on the thermal resistance of
      both strains was significantly lower at pH 2.5 and NaCl 8%, the number of viable
      cells decreased from approximately 10(8) CFU/ml to an undetectable number within
      20 min for strain EC1 and 15 min for strain EC2, respectively. This study
      indicates that heat resistance of strain EC1 was enhanced after acid or thermal
      adaptation. Heat resistance of strain EC2 was, however, enhanced only after
      thermal adaptation. For both strains no relationship was found between salt
      adaptation and the ability to resist thermal stress.

PMID- 18088013
TI  - An origin of transfer from Lactococcus lactis subsp. lactis causes rearrangement
      in the temperature sensitive plasmids pUCB3522 and pJRS290.
AB  - Cloning of the oriT region derived from Lactococcus lactis subsp. lactis into
      plasmids is expected to convert them into mobilizable plasmids in a suitable
      genetic background. In some cases, however, the cloning of oriT causes
      deleterious DNA rearrangements. In the work presented, oriT was cloned into two
      temperature sensitive plasmids, pJRS290 and pUCB3522. The plasmids were
      transformed into E. coli and electroporated into L. lactis. Restriction digestion
      of the plasmids derived from the cloned transformed cells showed fragment sizes
      different from those expected, indicating that rearrangements had occurred.
      Furthermore, the inability to successfully transform E. coli with one of the
      plasmids supports this conclusion.

PMID- 18088014
TI  - Antituberculotic drug resistance in a Turkish state hospital with national data.
AB  - Antituberculosis drug resistance is a major factor threatening the success of
      tuberculosis control programmes. The aim of this study was to reveal the patterns
      of antituberculosis drug resistance in a secondary hospital in Turkey and to
      compare with national data. The results of BACTEC MGIT 960 system for
      susceptibility testing were retrospectively analysed on 76 clinical Mycobacterium
      tuberculosis complex isolates from different patients. The mean age of 48 men
      (63.2%) and 28 women was 37 and 39, respectively. Overall resistance rate to
      isoniazid was 14.5%, followed by streptomycin 9.2%, ethambutol 6.9% and rifampin
      5.3%. Female sex and diabetes mellitus but not the presence of cavitary lesion or
      radiological involvement was a risk factor for the development of drug
      resistance. Anemia, leukocytosis or thrombocytosis was not associated with the
      drug resistance. In conclusions, further studies should be conducted regularly to
      monitor drug resistance in Turkey in order to manage effectively national
      tuberculosis control efforts.

PMID- 18088015
TI  - Methodological issues in the diagnostic work-up of food allergy: a real
      challenge.
AB  - The standard of reporting in diagnostic studies has generally been low.
      Fortunately, this issue has begun to be addressed in recent years through the
      discussion of important methodological issues in educational series, textbooks,
      and checklists. Double-blind, placebo-controlled, oral food challenges (DBPCFC)
      are considered to be the gold standard for diagnosis of food allergy. However,
      there is no consensus regarding how to interpret the outcome and how to define
      positive and negative provocations in DBPCFC. Furthermore, since most theories on
      the diagnosis of food allergy rely on the assumption that the DBPCFC has a high
      accuracy, this accuracy must be formally statistically evaluated. In this review,
      we discuss essential methodological issues for diagnostic accuracy studies in
      general and for oral food challenges in particular and discuss the importance of
      methodological issues as a guide for forthcoming studies of diagnostic
      procedures.

PMID- 18088016
TI  - Hymenoptera venom allergy: taking the sting out of difficult cases.
AB  - BACKGROUND: Correct identification of the culprit venom is a prerequisite for
      specific venom immunotherapy. OBJECTIVE: To assess whether the basophil
      activation test (BAT) constitutes an additional diagnostic instrument in patients
      with equivocal or negative specific immunoglobulin (Ig) E or venom skin test
      (VST) results. METHODS: One hundred eighteen patients with a compelling history
      of IgE-mediated hymenoptera venom allergy were enrolled. Venom-specific IgE was
      quantified by ImmunoCAP and VST was performed in all patients. Basophil
      activation was analyzed by flow cytometry after labeling with anti-IgE and anti
      CD63. RESULTS: In 64 out of 118 patients, diagnosis was considered as definite
      and the entomologic description was confirmed by unequivocal and concordant
      positive specific IgE and VST results. In 53 of those 64 patients, BAT confirmed
      diagnosis, whereas the remaining 11 patients were nonresponsive in the BAT
      analysis. Forty-seven patients (40%) had a tentative diagnosis of venom allergy,
      as they had divergent specific IgE or VST results. In 31 of those patients, BAT
      was positive only for the suspected venom and helped to establish diagnosis of
      wasp and honeybee venom allergy in 28 and 3 patients, respectively. BAT was
      diagnostic in 7 patients with complete negative results for specific IgE and VST,
      despite clear entomologic identification. CONCLUSIONS: In about half the patients
      with diagnosis of venom allergy, unequivocal specific IgE and VST results are
      obtained and additional tests are not needed. In the remainder, diagnosis is less
      straightforward due to discrepant or negative specific IgE orVST results. In
      these patients, BAT constitutes a helpful additional instrument to identify the
      culprit venom and start venom immunotherapy accordingly.

PMID- 18088017
TI  - Association of TNF-alpha -308 G/A and IL-4 -589 C/T gene promoter polymorphisms
      with asthma susceptibility in the south of Iran.
AB  - BACKGROUND: Both tumor necrosis factor alpha (TNF-alpha) and interleukin (IL) 4
      have been implicated in the pathogenesis of asthma. Furthermore, a G/A
      substitution at position -308 of the TNF-alpha gene promoter and a C/T
      substitution at position -589 of the IL-4 gene promoter have been associated with
      increased production of TNF-alpha and IL-4, respectively. OBJECTIVE: The aim of
      the present study was to analyze the association between TNF-alpha-308 G/A and IL
      4-589 C/T polymorphisms and susceptibility to asthma in a group of patients from
      southern Iran. METHODS: We analyzed the frequency of TNF-alpha -308 G/A and IL-4
      589 C/T polymorphisms in a total of 203 asthmatic patients compared to 113
      nonasthmatic control subjects. RESULTS: An association was observed between the
      TNF-alpha -308 G/A polymorphism and susceptibility to asthma in patients with a
      ratio between forced expiratory volume in 1 second and forced vital capacity of
      less than 75% compared with normal subjects; however, the association did not
      achieve statistical significance (P = .054). The IL-4-589 C/T polymorphism was
      associated with asthma susceptibility (P = .02). In addition, the association
      between this polymorphism and asthma severity approached statistical significance
      (P = .07). CONCLUSION: These results provide further evidence for a role of TNF
      alpha-308 G/A and IL-4-589 C/T polymorphisms in susceptibility to and severity of
      asthma. Further studies involving a larger number of patients may help to confirm
      our observations.

PMID- 18088019
TI  - Sublingual immunotherapy to house dust mite in pediatric patients with allergic
      rhinitis and asthma: a retrospective analysis of clinical course over a 3-year
      follow-up period.
AB  - BACKGROUND AND OBJECTIVE: Specific allergen immunotherapy is believed to be the
      only treatment able to change the natural history of allergic airway diseases.
      Sublingual immunotherapy (SLIT) is especially preferred because of its easy
      application and safety. The aim of this study was to describe the effect of SLIT
      in pediatric patients who have allergic airway disease. METHODS: Children with
      asthma and rhinitis who were allergic to house dust mite were evaluated. The
      effect on clinical course of 3 years of SLIT with 50% Dermatophagoides
      pteronyssinus and 50% Dermatophagoides farinae in a standardized extract was
      assessed retrospectively. RESULTS: The records of 39 patients (23 boys, 16 girls)
      were studied. The mean (+/- SD) age for starting SLIT was 8.8 +/- 2.3 years. The
      mean number of acute asthma attacks at the onset of the disease was 8.18 +/-
      3.05. The mean number of attacks after 3 years of SLIT was 0.44 +/- 0.79. There
      was a statistically significant difference in the number of acute asthma attacks
      before and after therapy (P < .001). Complete clinical remission of asthma was
      recorded in 37 (95%) patients. Similarly, complete clinical remission of allergic
      rhinitis was recorded in 32 (82%) patients. CONCLUSION: This retrospective study
      shows that SLIT is effective in children who have allergic airway disease which
      cannot be controlled effectively with allergen avoidance measures only.

PMID- 18088018
TI  - Prevalence and risk factors for asthma in Poland: results from the PMSEAD study.
AB  - BACKGROUND: The prevalence of asthma depends on both hereditary and environmental
      factors. Knowledge of the effects of environmental and congenital factors on the
      frequency of occurrence of asthma may provide important clues to its pathogenesis
      and prevention. OBJECTIVES: The Polish Multicentre Study of Epidemiology of
      Allergic Diseases was designed to obtain estimates representative of the entire
      Polish population to assess asthma prevalence and risk factors. METHODS: Thirty
      three areas were selected in 11 regions of Poland. Epidemiologic diagnoses of
      asthma were verified by a single recognized expert in each region on the basis of
      collected data as well as available medical documentation, in accordance with the
      1997 guidelines of the Global Initiative for Asthma. Ambient air concentrations
      of sulfur dioxide and suspended particulates (black smoke) were measured directly
      or estimated by statistical modelling. RESULTS: Results were obtained for asthma
      in 16 238 subjects, including 3268 children (aged 3 to 16 years) and 12 970
      adults (17 to 80 years). The overall prevalence of asthma was 8.6% (95%
      confidence interval [CI], 7.7%-9.6%) among children and 5.4% (95% CI, 5.0%-5.8%)
      among adults. Several risk factors for asthma were identified: family history of
      asthma, black smoke, residential exposure to traffic-related air pollution in
      both children and adults, and damp or overcrowded housing in adults. No
      statistically significant association was observed for passive smoking in the
      home, use of gas stoves, pet ownership, or exposure to ambient air pollution with
      sulfur dioxide. CONCLUSION: Our results show that the prevalence of asthma is
      associated with several host and environmental factors in the Polish population.

PMID- 18088020
TI  - Expression of inducible nitric oxide synthase in a mouse model of anaphylaxis.
AB  - BACKGROUND: The generation of large quantities of nitric oxide (NO) is implicated
      in the pathogenesis of anaphylactic shock. The source of NO, however, has not
      been established and conflicting results have been obtained when investigators
      have tried to inhibit its production in anaphylaxis. OBJECTIVE: The aim of this
      study was to analyze the expression of inducible nitric oxide synthase (iNOS) and
      endothelial nitric oxide synthase (eNOS) in a mouse model of anaphylaxis.
      METHODS: BALB/c mice were sensitized and challenged with ovalbumin to induce
      anaphylaxis. Tissues were removed from the heart and lungs, and blood was drawn
      at different time points during the first 48 hours after induction of
      anaphylaxis. The Griess assay was used to measure nitric oxide generation. Nitric
      oxide synthase expression was examined by reverse transcriptase polymerase chain
      reaction and immunohistochemistry. RESULTS: A significant increase in iNOS mRNA
      expression and nitric oxide production was evident as early as 10 to 30 minutes
      after allergen challenge in both heart and lungs. In contrast, expression of eNOS
      mRNA was not altered during the course of the experiment. CONCLUSION: Our results
      support involvement of iNOS in the immediate physiological response of
      anaphylaxis.

PMID- 18088021
TI  - Predicting patients at high-risk of systemic reactions to cluster allergen
      immunotherapy: a pilot prospective observational study.
AB  - OBJECTIVE: The purpose of this study was to identify factors associated with
      increased risk of adverse systemic reactions to cluster allergen immunotherapy
      and to create a preliminary predictive clinical model. METHODS: In a prospective
      observational study, the tolerance of 611 patients with seasonal respiratory
      diseases who were receiving cluster immunotherapy was monitored and all systemic
      reactions were recorded. Associations between potential prognostic factors (sex,
      age, respiratory disease, severity, duration of disease, previous immunotherapy,
      nonseasonal symptoms, skin prick test, total immunoglobulin (Ig) E, specific IgE,
      treatment schedule, allergenic composition, batch, date of treatment, habitat,
      place of residence) and systemic reactions were estimated. Multivariate stepwise
      logistic regression analysis was used to build a predictive clinical model and
      estimate the probability of systemic reactions to cluster immunotherapy. RESULTS:
      Sixty-five patients (10.6%) suffered systemic reactions. Only 7 independent risk
      factors were retained in the final model: age over 14 years (odds ratio [OR],
      2.6), previous immunotherapy (OR, 0.3), skin prick test positive to Chenopodium
      album (white goosefoot) (OR, 3.0), elevated specific IgE to grass pollen (OR,
      2.3), elevated specific IgE to olive pollen (OR, 4.1), olive pollen 100%
      composition (OR, 2.6) and treatment schedule (OR, 1, 1.6 or 7.1, depending on the
      cluster immunotherapy schedule). CONCLUSIONS: This predictive model, derived from
      simple clinical variables, has excellent ability to assess individual risk of
      suffering systemic reactions to cluster allergen immunotherapy. Detecting high
      risk patients can help clinicians to prevent and eliminate many severe adverse
      reactions to cluster immunotherapy.

PMID- 18088022
TI  - In vivo diagnostic tests in adverse reactions to quinolones.
AB  - BACKGROUND AND OBJECTIVE: Contradictory reports of the sensitivity of skin tests
      in quinolone allergy have been reported. Our objectives were to describe the
      outcome of quinolone skin and challenge tests in patients consulting because of a
      history of adverse reaction to quinolone and to compare the outcome of quinolone
      skin tests and challenge tests in the subsample of patients who had undergone
      both tests. METHODS: We reviewed skin and challenge test results of all patients
      who consulted at our allergy service over the last 5 years because of a history
      of quinolone adverse reaction in the form of urticaria or anaphylaxis within 1
      hour of drug intake (group 1), urticaria or maculopapular eruption between 1 and
      24 hours after intake (group 2) or after 24 hours had passed (group 3), or
      atypical symptoms (group 4). RESULTS: A total of 71 cases were identified: 27, 8,
      24 and 12 in groups 1 through 4, respectively. Skin tests were performed in all
      patients, with positive results in 31 patients. In group 1, 62.9 % of these
      patients showed positive skin tests and 22.2% showed positive challenge tests,
      whereas in the other 3 groups, about 30% of patients had positive skin tests and
      a variable percentage (from 0% to 4.1% depending on the group) had positive
      challenge tests. Quinolone challenge tests were performed in 10 patients with
      positive skin tests (5 of them with positive results) and in 34 patients with
      negative skin tests (2 of them with positive results). CONCLUSIONS: A highly
      suggestive history of quinolone allergy is more frequently associated with
      positive skin tests and positive challenge tests. Therefore, skin tests help to
      predict the result of the challenge test.

PMID- 18088023
TI  - Efficacy and quality of life with once-daily sublingual immunotherapy with
      grasses plus olive pollen extract without updosing.
AB  - OBJECTIVE: The purpose of this randomized, double-blind, placebo-controlled study
      was to evaluate the clinical efficacy and tolerance of once-daily sublingual
      immunotherapy without updosing. Reduction in symptoms and medication use was the
      primary endpoint. METHODS: One hundred five patients with rhinitis and/or asthma
      due to grass and olive sensitization were randomized to be treated with placebo
      or active sublingual immunotherapy with the SLITone grass mix plus olive pollen
      extract for 6 months before the 2005 pollen season. Patients recorded symptoms
      and medication intake for 8 weeks during the pollen seasons in 2004 (n=37) and
      2005 (n=85). RESULTS: Allergic symptoms were significantly decreased in the
      active immunotherapy group (P = .004) but not in the placebo group. There were no
      differences in scores between groups during the 2005 pollen season. Subjective
      assessments on a visual analog scale and a quality-of-life questionnaire
      indicated an improvement in actively treated patients with significant
      differences in both symptoms and medication use (P = .006). The rate of systemic
      adverse reactions was comparable in the 2 groups. No anaphylactic or severe
      adverse reactions were reported. Local adverse reactions, which were more common
      in the active immunotherapy group, were mostly immediate, were limited to the
      lips and mouth, and did not require treatment. CONCLUSION: Once-daily sublingual
      immunotherapy without updosing was well tolerated. The actively treated patients
      showed a significant reduction in symptom and medication scores and an
      improvement in their quality of life although there were no significant
      differences between the groups probably due to the low allergen season in which
      the study was evaluated.

PMID- 18088024
TI  - Aniseed-induced nocturnal tongue angioedema.
AB  - Aniseed is a spice native to the eastern Mediterranean region. Cases of
      simultaneous hypersensitivity to celery, mugwort pollen, and spices of the
      Umbelliferae family have been described as the celery-mugwort-spices syndrome. We
      report a case of aniseed-induced tongue angioedema. Skin prick tests to foods
      proved positive only to aniseed. Serum-specific immunoglobulin (Ig) E
      determination by enzyme allergosorbent test was 0.4 kU/L to aniseed extract and
      0.6 kU/L to tare and cumin seeds. The molecular mass of the IgE-binding proteins
      studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      immunoblotting revealed a broad IgE-binding band of 12.9-13.7 kd in aniseed and
      tare extract assays and a broad band of 15-17.5 kd in cumin extract. This is the
      first case of type I hypersensitivity due to aniseed liqueur ingestion reported.
      SDS-PAGE immunoblotting study showed a broad specific IgE-binding band of 12.9
      13.7 kd when aniseed extract was incubated with the patient's serum; this band
      might correspond to the protein responsible for the described symptoms.

PMID- 18088025
TI  - Allergy to cassava: a new allergenic food with cross-reactivity to latex.
AB  - Patients who are allergic to latex (Hevea brasiliensis) may exhibit cross
      hypersensitivity with foods. We present a case of anaphylaxis due to cassava in a
      patient suffering from pollinosis, latex allergy, and latex-fruit syndrome. We
      performed sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      and immunoblotting with cassava, avocado, chestnut, banana, kiwi, and latex
      extracts in order to analyze the protein bands and their molecular weights, and
      identify immunoglobulin (Ig) E-binding bands. Immunoblot inhibition and enzyme
      linked immunosorbent assay (ELISA) inhibition were performed with latex in order
      to assess cross-reactivity. Cassava exhibited numerous protein bands, 5 of which
      were IgE-binding (89.75, 46.28, 26.68, 21.38, and 19.49 kd). These cassava IgE
      binding bands were 100% inhibited by preincubation of the patient's serum with
      latex extract. The ELISA inhibition between latex and cassava was 23%. Our
      results confirm cassava as another food with clinical cross-reactivity in
      patients suffering from latex allergy.

PMID- 18088026
TI  - Secretion of interleukin 4 and immunoglobulin G from peripheral blood mononuclear
      cells in allergic rhinitis.

PMID- 18088027
TI  - Flare-up-Like phenomenon in a skin prick test after oral challenge with
      ibuprofen.

PMID- 18088028
TI  - No association between placental weight or ratio at birth and risk of atopy, hay
      fever, or asthma at the age of 31 years.

PMID- 18088029
TI  - Hypersensitivity to spiramycin with good tolerance of other macrolides.

PMID- 18088030
TI  - Food-induced anaphylaxis caused by inhalation of soy protein.

PMID- 18088031
TI  - Control of asthma and utilization of medical resources: results from a community
      pharmacies study in the Navarre region of Spain.

PMID- 18088032
TI  - Anaphylactic reaction after intake of phenylephrine and tolerance of other
      sympathomimetic drugs.

PMID- 18088033
TI  - Contact urticaria to phthalic anhydride.

PMID- 18088034
TI  - [Immune recovery vitritis].
AB  - INTRODUCTION: Immune recovery vitritis (IRV) is symptomatic vitritis of > 1 +
      severity associated with inactive cytomegalovirus (CMV) retinitis. It is an
      opportunistic infection of the eye, in the patients who suffer from AIDS, and is
      treated with a highly active antiretroviral therapy (HAART). As a result of this
      therapy, there is an immune reconstitution in the body and inflammation of the
      vitreous body. OBJECTIVE: The aim of the study was to show the incidence of IRV
      in patients treated with HAART. METHOD: A retrospective study was conducted in
      patients who suffered from CMV retinitis. Twenty-one were treated with HAART and
      had the diagnosis of CMV retinitis, as well. All of them were examined by the
      same ophthalmologist who peformed slit lamp examination with mydriasis and
      indirect ophthalmoscopy. RESULTS: Nine of 21 patients developed IRV as a
      complication of HAART, two had cystoid macular oedema (CMO). CONCLUSION: CMV
      retinitis develops when the number of CD4+ T lymphocytes drops below 50/mm3. This
      results in necrotic retinitis which, if untreated, leads to complete loss of
      vision. With the introduction of HAART, we learned that the reconstitution of
      immune status was achieved as well as life expectancy, but there was a dramatic
      decline in the opportunistic infection, including CMV retinitis, as well. With
      the immune reconstitution, the inflammation develops in the eye, known as IRV.
      Sometimes, it is neccessary to treat this condition, but in the case of our
      patients, the inflammation was mild, and no treatment was neccessary.

PMID- 18088035
TI  - [Effects of continuous physical training on exercise tolerance and left
      ventricular myocardial function in patients with heart failure].
AB  - INTRODUCTION: Physical training is an important method in the rehabilitation
      programme for cardiovascular patients. Nevertheless, some controversies about
      physical training in patients with heart failure still exist. OBJECTIVE: The aim
      of the study was to assess the effects of continuous physical training on
      exercise tolerance, ejection fraction and regional systolic and diastolic left
      ventricular (LV) myocardial function in patients with stable heart failure.
      METHOD: The study involved 48 male patients with stable heart failure and LV
      ejection fraction < or =35% determined by echocardiography. At the end of a two
      week residential rehabilitation programme, the patients were divided in two
      groups. The group of 27 patients (T group) continued with regular physical
      training (4 to 5 times weekly) during 6 months, while 21 patients (K group) did
      not have regular physical training. In all patients, the exercise test and
      echocardiography studies were performed after residential rehabilitation and 6
      months later. Regional myocardial function of LV was evaluated by the pulsed wave
      tissue Doppler imaging. RESULTS: After 6 months, an increase in exercise
      tolerance was more significant in T group. LV ejection fraction increased
      significantly (p < 0.05) only in T group. After six months, in T group, regional
      systolic (p < 0.01) and diastolic (p < 0.005) myocardial function improved
      significantly, while in K group a significant improvement was seen only for
      regional diastolic function (p < 0.05), and it was less than in T group.
      CONCLUSION: The results of our study suggest that continuous physical training
      during the period of 6 months in patients with stable heart failure induced
      significant improvement of exercise tolerance, ejection fraction and regional
      systolic and diastolic LV myocardial function.

PMID- 18088036
TI  - [Treatment of acute ST elevation myocardial infarction with primary percutaneous
      coronary intervention in Department of Cardiology, Clinical Centre of Serbia,
      Belgrade: movement and treatment of patients from the onset of chest pain till
      the attempt of reopening the infarct-related artery].
AB  - INTRODUCTION: Treatment of patients with acute ST elevation myocardial infarction
      starts after the onset of chest pain, involves contacts with medical services,
      aimed at attempting to recanalize the infarct-related artery with primary
      percutaneous coronary intervention. True ischaemic time correlates with the
      extent of myocardial necrosis, and it is essential to reduce every unnecessary
      time loss. It has been proven that antiaggregational therapy has an important
      effect on reopening of the infarct-related artery, function of microcirculation
      and prevention of stent thrombosis. OBJECTIVE: The aim of this study was to
      determine movement and treatment of patients, from the onset of symptoms till
      leaving the catheterization laboratory, and, if necessary, to propose corrections
      according to medical guidelines and medicolegal obligations. METHOD: This study
      presents a part of a larger project, designed in three phases. Here are presented
      the first two completed phases. The first phase enrolled the total of 228
      patients, with retrospective acquisition of data from the medical documentation.
      In the second phase, the total of 277 patients were enrolled, and data were
      collected with special graphico-textual form upon the patient's arrival to the
      catheterization lab. Data were checked with the First-Aid Station of Belgrade and
      the Department of Emergency Cardiology of our Clinic. In the third phase, it has
      been planned to improve the graphico-textual form and to distribute it to all
      institutions involved in treatment of these patients. RESULTS: The patients
      mainly moved centrifugally--from the catheterization lab (in this manner, 95% of
      patients were transferred by the first-aid station, and 31% patients were sent
      from other hospitals), instead of centripetally--towards the catheterization lab.
      The median time of reaction of the First-Aid Station of Belgrade was 15 minutes.
      The median of true ischaemic time was 260 minutes; the median time from the onset
      of chest pain to diagnostic ECG was 60 minutes, while the median time from
      diagnostic EKG to the first balloon inflation was 177 minutes. Upon arrival to
      the catheterization lab, a median of 18 minutes passed till the insertion of the
      catheter, and the median procedure duration was 35 minutes. Dual
      antiaggregational therapy was administered relatively late on the way to the
      catheterization lab (the first-aid station missed the opportunity to administer
      clopidogrel in 84% of patients, aspirin in 86%, other hospitals did not
      administer clopidogrel in 40% and aspirin in 41% of patients). CONCLUSION:
      Optimal medical data acquisition is essential for the quality assessment of
      health services. Our data indicate that in logistics and organization of
      treatment of patients with acute ST elevation myocardial infarction, further
      improvements could be made in order to implement official guidelines and
      medicolegal obligations. The third phase of this project is necessary to achieve
      these objectives.

PMID- 18088037
TI  - [Ultrasonography findings of liver in textile workers for diagnosing nonalcoholic
      fatty liver disease].
AB  - INTRODUCTION: Ultrasonography, as a non-invasive method, has the advantage over
      other imaging methods in the investigation of nonalcoholic fatty liver disease
      (NAFLD), related to risk factors. OBJECTIVE: The aim of the study was to present
      the value of ultrasound imaging of fatty liver during a routine checkup of the
      selected working population. Fatty liver was related to obesity and
      hyperlipidaemia, excluding alcohol and diabetes mellitus. METHOD: 120 textile
      workers were examined by ultrasound; blood cholesterol and triglycerides were
      measured in the meantime. Ultrasonography finding in the liver was normal
      echogenicity or "bright" hyperechogenicity (fatty liver). Five subgroups of
      examinees were formed using three risk factors for fatty liver: Body Mass Index
      (BMI), blood cholesterol and triglycerides. RESULTS: Ultrasonographic appearance
      of the liver was normal in 55% of examinees, while 45% had fatty liver.The
      highest incidence of fatty liver (70%) was in the first subgroup with the highest
      risk (elevated BMI, elevated cholesterol and triglycerides). The highest
      incidence od normal liver (85%) was in the fifth subgroup without risk factors
      (normal BMI, normal blood cholesterol and triglycerides). Incidence of fatty
      liver between subgroups was very different with high statistical significance.
      CONCLUSION: Increased fat accumulation in the liver may be diagnosed with
      ultrasonography and related to risk factors for nonalcoholic fatty liver disease
      (NAFLD), such as obesity and hyperlipidaemia.

PMID- 18088038
TI  - [Frequency of Helicobacter pylori infection in patients with liver cirrhosis].
AB  - INTRODUCTION: Ulcer disease occurrence is increased among patients with liver
      cirrhosis. It is widely accepted that Helicobacter pylori infection is important
      in aetiology of ulcer disease. The role of Helicobacter pylori infection in
      pathogenesis of ulcer disease in patients with liver cirrhosis has not been
      satisfactorily explored yet. OBJECTIVE: The aim of this study was to determine
      frequencies of Helicobacter pylori infection in patients with liver cirrhosis in
      relation to the aetiology of cirrhosis, clinical stage and concomitant ulcer
      disease. METHOD: We studied 50 patients with liver cirrhosis analysing the
      aetiology of liver cirrhosis, clinical stage, presence of ulcer disease, and
      existence of Helicobacter pylori infection. Results were thoroughly analysed and
      compared. RESULTS: Among 50 studied subjects, 37 were male (average age 56.62 +/-
      10.47 years), while 13 were female (average age 60.69 +/- 6.51 years). In 32
      (64%) patients, liver cirrhosis was related to alcohol abuse, whereas in
      remaining 16 (36%) subjects, cirrhosis was due to chronic viral infection. Ulcer
      disease, determined by endoscopy, was present in 8 (16%) patients, although 18
      (36%) subjects were Helicobacter pylori positive. There were no significant
      differences in occurrences of Helicobacter pylori infection amongst the patients
      with and without ulcer disease (chi2 = 0.923; p > 0.05). No significant
      difference was found for the clinical stage and type of ulcer disease (chi2 =
      0.869; p > 0.05). The difference in presence of Helicobacter pylori infection and
      aetiology of liver cirrhosis appeared to be of no significance, either (F =
      0.540; p > 0.05). The presence of Helicobacter pylori infection in different
      clinical stages seemed to be of statistical significance (chi2 = 7.0; p < 0.05).
      CONCLUSION: The obtained results indicate that the prevalence of Helicobacter
      pylori infection in patients with liver cirrhosis is lower compared to general
      population, and that is of no significance for ulcer disease in these subjects.
      Moreover, it is likely that the frequency of Helicobacter pylori infection in
      patients with liver cirrhosis is not related to the aetiology of cirrhosis, while
      this infection seems to be more frequently present in severe clinical forms of
      hepatic cirrhosis.

PMID- 18088039
TI  - [Echocardiographic evaluation of ventricular septal defect haemodynamics].
AB  - INTRODUCTION: Ventricular septal defect (VSD) is an opening in the
      interventricular septum. 30-50% of patients with congenital heart disease have
      VSD. OBJECTIVE: The aim of the study was to determine the dependence of the left
      ventricular diastolic dimension (LVD), left ventricular systolic dimension (LVS),
      shortening fraction (SF), left atrium (LA), pulmonary artery truncus (TPA) on the
      body surface and compare their values among experimental, control and a group of
      healthy children. Values of maximal systolic gradient pressure (Pvsd) of VSD were
      compared with children from one experimental and control group. METHOD: Children
      were divided into three groups: experimental (32 children with VSD that were to
      go to surgery), control (20 children with VSD who did not require surgery) and 40
      healthy children. Measurements of LVD, LVS, SF, LA, TPA were performed in
      accordance to recommendations of the American Echocardiographic Association. The
      value of Pvsd was calculated from the maximal flow velocity (V) in VSD using the
      following formula: Pvsd = 4 x V2 (mm Hg). RESULTS: For children from the
      experimental group, the relationship between the body surface and the variability
      of the LVD was explained with 56.85%, LVS with 66.15%, SF with 4.9%, TPA with
      58.92%. For children from the control group, the relationship between the body
      surface and the variability of LVD was explained with 88.8%, LVS with 72.5%, SF
      with 0.42%, PA with 58.92%. For healthy children, the relationship between the
      body surface and the variabilitiy of the LVD was explained with 88.8%, LVS with
      88.78%, SF with 5.25% and PA with 84.75%. There was a significant statistical
      difference between average values of Pvsd in the experimental and control group
      (p < 0.02). CONCLUSION: The presence of the large VSD has an influence on the
      enlargement of LVD, LVS, SF,TPA. The enlargment of the size of the pulmonary
      artery depends on the presence of VSD and there is a direct variation in the
      magnitude of the shunt. There is a relationship and significant dependence of the
      LVS and LVD on the body surface. There is no statistically significant dependence
      between SF and body surface.

PMID- 18088040
TI  - [Relationship between degree of dyspnoea and health-related quality of life in
      patients with chronic obstructive pulmonary disease].
AB  - INTRODUCTION: Dyspnoea is a characteristic symptom of chronic obstructive
      pulmonary disease (COPD), which impairs everyday functioning of patients.
      OBJECTIVE: The aim of our study was to evaluate the relationship between the
      degree of dyspnoea of COPD patients and their health-related quality of life.
      METHOD: We measured the degree of dyspnoea and health-related quality of life in
      85 COPD outpatients (46 male; mean age was 58 +/- 12 years; mean forced
      expiratory volume in one second (FEV,) was 47.9 +/- 18.6% predicted). The degree
      of dyspnoea was assessed by Baseline Dyspnoea Index (BDI), List of Daily
      Activities (DAL), Visual Analogue Scale (VAS), Modified MRC Dyspnoea Scale, and
      Borg Category Scale (BCS). The patients filled two standardized questionnaires
      for measuring health-related quality of life: the generic one--15D, and the
      respiratory specific one--the St. George's Respiratory Questionnaire (SGRQ).
      Total 15D and SGRQ scores, as well as the scores for individual domains of SGRQ
      (symptoms, activity and impact scores) for each patient were calculated. In 40
      out of 85 patients, the same procedure was repeated at the follow-up, with a mean
      4-week interval between the visits. RESULTS: There were statistically highly
      significant correlations (p < 0.01) between values of all dyspnoea scale scores
      evaluated and all the health-related quality of life scores. The highest degree
      of correlation of both total SGRQ and 15D scores was found for the values of BCS
      (r = 0.731 and -0.776, respectively). A statistically significant correlation
      between the changes of all SGRQ (but not 15D) scores and all dyspnoea score
      changes (except for MRC) were also recorded. CONCLUSION: The degree of dyspnoea
      of COPD outpatients that could be well-determined by the scales used in our study
      clearly reflects the impairment of their health-related quality of life as
      assessed by the instruments used. All of the questionnaires we used in this study
      have good measurement properties for their purposes.

PMID- 18088041
TI  - [The effect of medicamentous and non-medicamentous therapy on lowering risk
      factors for cardiovascular and cerebrovascular episodes in an interventional
      study].
AB  - INTRODUCTION: In a chain of cardiovascular episodes, risk factors (RF) and bad
      habits represent the first link. OBJECTIVE: The purpose of the study was to
      determine, during six months, on four examinations (the first, and three follow
      ups after the second, fourth and sixth month), the following: physical activity
      (PA) alteration and the number of cigarettes smoked; the effect of
      antihypertensive beta-blockers and ACE inhibitors on systolic and diastolic
      arterial tension; the effect of metmorfin therapy on BMI, glycaemia, total
      cholesterol level (TCL) and triglycerides in diabetics compared to healthy
      individuals; the effect of hypolipidaemics on blood TCL and triglycerides in
      patients with angina pectoris (AP); the effect of betablocker therapy on TCL.
      METHOD: This was a multicentric interventional study. Secondary prevention of
      coronary disease and cerebrovascular conditions was applied in the first half of
      2005. There were 185 general practitioners from 38 health centres in Serbia, and
      patients of both sexes were included with the verified diagnosis of coronary
      disease and/or cerebrovascular condition. They had demographic data verified as
      well as data of being genetically (non)predisposed for AP, hypertension,
      myocardial infarction, stroke and diabetes mellitus. Descriptive and differential
      statistical methods were used for study result analysis. RESULTS: Out of 1189
      patients, there were 51.4% of women and 48.6% of men. The average age was 59.45
      +/- 9.77 years. The population was homogeneous by sex and the factor of being
      genetically (non)predisposed for AP. There was a significant difference in
      examinations in four contacts in PA and cigarette smoking (p < 0.0001). Systolic
      and diastolic pressure, TCL and triglycerides were significantly decreased by
      medicaments (p < 0.05) and more significantly so associated with nonmedicamentous
      measures (p < 0.001). Metmorfin significantly decreased the glycaemic level (p <
      0.001) both in diabetics and patients with a reduced tolerance level to glucose.
      In patients who took betablockers, there was lowering of TCL. CONCLUSION: Taking
      medicaments significantly lowers RF, and more significantly so when associated
      with a non-medicamentous therapy.

PMID- 18088042
TI  - [Posterior cusp enlargement in mitral valve reconstructive surgery for
      restrictive valve insufficiency--case report].
AB  - INTRODUCTION: According to Carpentier classification, group III of mitral
      insufficiency is caused by the restrictive motion of the mitral valve. A
      rheumatic process and a coronary disease are the main causes. It is very
      important to examine the valve precisely, to define deformities and aetiology in
      order to make such a valve functional. In rheumatic disease, fibrosis and
      degeneration deform the entire mitral apparatus. A surgical principle is to re
      establish mobility and pliability of the apparatus taking care of the functional
      anatomy at the same time. Cusp enlargement, chordal mobilization and ring
      remodelling arejust some of the numerous surgical techniques that could be
      performed in these patients. CASE OUTLINE: A 55-year-old female patient was
      admitted to hospital with severe mitral regurgitation. She belonged to NYHA,
      functional stage 2. Echocardiography revealed that both cusps, mostly posterior,
      were of reduced size and mobility, resulting in grade 3 regurgitation. We
      performed posterior cusp enlargement by using autologous pericardium treated in
      0.6% of glutaraldehyde solution. Annulus remodelling was done using size 27
      flexible Duran ring. Control echocardiography found trivial regurgitation. The
      patient was discharged on 12th postoperative day in sinus rhythm. CONCLUSION:
      Surgical reconstruction of the rheumatic mitral valve back to the functional
      state is a demanding procedure, which, however, provides certain benefit for the
      successfully treated patient.

PMID- 18088043
TI  - [Transient neonatal pseudohypoparathyroidism].
AB  - INTRODUCTION: Pseudohypoparathyroidism (PHP) is a heterogeneous group of diseases
      characterized by end organ unresponsiveness to parathormone (PTH), due to
      receptor or postreceptor defects. The characteristic biochemical disturbances
      include hypocalcaemia, hyperphosphataemia and high serum parathormone levels.
      CASE OUTLINE: We present a 17-day-old male baby who was brought to our hospital
      because of seizures. He was found to have hypocalcaemia, hyperphosphataemia and
      an elevated serum level of parathyroid hormone. The diagnosis of PHP was based on
      the elevated serum level of PTH during hypocalcaemia and persistence of
      normocalcaemia after administering alphacalcidiol with oral calcium. After 4
      months of therapy, with tapering of the oral calcium doses, the treatment was
      discontinued. During the following six months without therapy, the infant did not
      have seizures and the serum levels of calcium and phosphorus were normal, so we
      established the final diagnosis of transient neonatal pseudohypoparathyroidism.
      CONCLUSION: At the time when the newborn was diagnosed to have PHP, there was no
      indication whether it was of a permanent or transient form. A considerably lower
      number of patients have a transitory form of PHP, which is then confirmed in the
      infant period by a gradual reduction and withdrawal of therapy, with sustaining
      serum calcium and PTH within normal limits.

PMID- 18088044
TI  - [Pulmonary sclerosing haemangioma--case report].
AB  - INTRODUCTION: Sclerosing haemangioma is a benign tumour, also known under the
      term "pneumocytoma". It is mostly notified in older females and is usually
      solitary. According to the histological appearance, sclerosing haemangioma could
      be: papillary, sclerotic, solid and haemorrhagic. CASE OUTLINE: A 68-year-old
      female patient was radiologically diagnosed with coin lesion in the lower right
      lobe. Lower right lobectomy was performed after clinical investigations. In
      pulmonary parenchyma, there was found a well circumscribed node of up to 35 mm in
      maximal diameter. The tumour was histologically established as sclerosing
      haemangioma, containing two types of cells with the same immunophenotype. A
      multiple type of tumour was excluded by postoperative radiological examinations.
      Two years after surgery, the patient is without disease recurrence. CONCLUSION:
      Sclerosing haemangioma should be considered in patients with radiologically
      diagnosed "coin-like" lesions of a solid as well as multiple type.

PMID- 18088045
TI  - [Uterine torsion in term pregnancy].
AB  - INTRODUCTION: Uterine torsion has been defined as a rotation of more than 45
      degrees of the uterus around its long axis that occurs at the junction between
      the cervix and the corpus. The extent of the rotation is usually 180 degrees,
      although cases with torsion from 60 to 720 degrees have been reported.
      Aetiopathogenesis of this condition is still unclear. Establishing clinical
      diagnosis of this condition is difficult, but very important for reducing
      maternal and foetal morbidity and mortality. Clinical symptoms are either absent
      or nonspecific, and the diagnosis is usually made at laparotomy. CASE OUTLINE: A
      31-year-old patient was admitted to the Institute of Gynaecology and Obstetrics,
      Clinical Centre of Serbia, Belgrade, as an emergency, seven days upon the
      established intrauterine foetal demise in the 40th gestation week. On uterine
      examination, the cervical length of 1.5 cm and dilatation of 3 cm were
      determined, as well as a palpable soft tissue formation, not resembling placenta
      praevia. Ultrasound examination confirmed foetal demise and exclusion of the
      presence of placenta praevia. The labour was completed by caesarean section.
      During surgery, uterine torsion of 180 degrees to the right was diagnosed. There
      was a stillborn male baby, and the cause of death was intrauterine asphyxia. A
      fibrosing and calcified accessory lobe 9 x 6 x 2.5 cm in size was observed on
      placental examination, which is a possible sign of initial gemellary pregnancy.
      CONCLUSION: The clinical presentation of uterine torsion is variable and clinical
      examination and ultrasonographic scanning may be insufficient for diagnosis. The
      method of choice for establishing the diagnosis is magnetic resonance imaging.
      Once the diagnosis of uterine torsion in pregnancy is established, emergency
      laparotomy is indicated. Following caesarean delivery, it is necessary to
      surgically remove all the anatomical causes of torsion, and rotate the uterus
      back to its normal position. There are some authors who suggest bilateral
      plication of the round ligaments as a preventive procedure for repeated torsion
      in puerperium and following pregnancies. The effectiveness of this method
      requires further investigation. It is necessary to have in mind the possibility
      of uterine torsion in all cases of abdominal pain during pregnancy and dystocia.

PMID- 18088046
TI  - [Diabetic cardiomyopathy: old disease or new entity?].
AB  - Cardiovascular manifestation of diabetes has remarkable therapeutic and
      prognostic implications. Diabetic cardiomyopathy is a distinct heart muscle
      disease in patients with well-controlled diabetes mellitus that cannot be
      ascribed to coronary artery disease, hypertension or any other known cardiac
      disease. It is characterized by left ventricular diastolic dysfunction that can
      be detected in 52-60% of well-controlled type II diabetic subjects using
      contemporary Doppler techniques. Pathophysiologically, hyperglycaemia causes
      myocardial necrosis and fibrosis, as well as the increase of myocardial free
      radicals and oxidants, which decrease nitric oxide levels, worsen the endothelial
      function and induce myocardial inflammation. Insulin resistance with
      hyperinsulinaemia and decreased insulin sensitivity are responsible for left
      ventricular hypertrophy. Clinical manifestations of diabetic cardiomyopathy are
      dispnoea, arrhythmias, atypical chest pain or dizziness. The treatment of
      diabetic cardiomopathy should be initiated as early as diastolic dysfunction is
      identified. Various therapeutic options include improving diabetic control with
      both diet and drugs (metformin and thiazolidinediones), use of ACE inhibitors,
      beta blockers and calcium channel blockers. Daily physical activity and reduction
      in body mass index may improve glucose homeostasis by reducing the
      glucose/insulin ratio, and the increase of both insulin sensitivity and glucose
      oxidation by the skeletal and cardiac muscles. Metformin and thiazolidinendiones
      are used to treat insulin resistance, but have different mechanisms of action.
      Metformin reduces free fatty amino acids effluvium from fat cells, thereby
      suppressing hepatic glucose production and indirectly improving peripheral
      insulin sensitivity and the endothelial function. In contrast, thiazolidinediones
      improve peripheral insulin sensitivity by reducing circulating free fatty amino
      acids, but also increasing production of adiponectin, which improves insulin
      sensitivity. Beta-adrenoceptor blocking agents are effective in preventing or
      reversing myocardial dilatation and remodelling, while ACE inhibitors facilitate
      blood flow through microcirculation in coronary vascular bed, fat and skeletal
      muscle, as well as improve insulin action at the cellular level.

PMID- 18088047
TI  - [Strategy and perspective of myocardial protection during ischaemia and
      reperfusion, and the role of volatile anaesthetics].
AB  - Surgical coronary revascularization is based on effectiveness of cardioplegia
      directed to protect myocardial functional integrity during periods of ischaemia
      and reperfusion. The aim of cardioplegia is to protect numerous intracellular
      processes: to spare the intracellular energy stores, to reduce free oxygen
      radical synthesis, to protect the function of the endothelium and myocardial
      oxygen balance as well as ionic balance. Crystalloid or blood cardioplegia, with
      anterograde or retrograde infusion, is a basic procedure of the intraoperative
      cardiac protection. Glucose-insulin-potassium (GIK) solution was primarily used
      in myocardial infarction. After the first promising results, some surgical teams
      started using a high glucose-insulin-potassium solution, as a metabolic
      modulation approach, during coronary surgery in addition to cardioplegia.The
      improvement of the left ventricular performances, rare rhythm disturbances and
      reduced need for inotropic support during the period of reperfusion justified the
      GIK beneficial effect. Further improvement in metabolic modulation during
      coronary surgery was made with fluorine ion halogenated volatile aneasthetics
      used for anaesthesia. Results of some experimental and first clinical studies
      have induced a new approach to modulation of the intracellular metabolic
      mechanisms and announced the new concept of anaesthetic preconditioning in
      coronary surgery. Large, randomized studies are needed to evaluate anaesthetic
      preconditioning and dependence of its efficiency on the type and dose of volatile
      anaesthetics.

PMID- 18088048
TI  - [Conventional and molecular methods in diagnosis and monitoring of viral
      infection].
AB  - Laboratory diagnosis of viral infections comprises a spectre of methods and
      techniques with different sensitivity and specificity that are used in routine
      and research laboratory work. Modern laboratory procedures in virology can be
      divided in two groups: conventional and molecular methods. Although some of them
      are widely used, none deserves the title "gold standard" for its diagnostic and
      prognostic value. Viral isolation in cell culture is now considered a non-routine
      method. A virus can be detected and initially identified through observation of
      virus-induced characteristic morphology changes in inoculated cells. Although
      isolation is a highly specific method, it has many limitations.Today, the
      existence of other, more rapid and sensitive techniques, confines viral isolation
      onlyto research work. Conventional techniques also include: identification of
      viruses based on their morphology by electron microscopy (EM), viral antigen
      detection using the immunofluorescence (IF) or immunoenzyme methods (ELISA). All
      the above-mentioned conventional methods have lower sensitivity and unreliability
      as disadvantages when compared to modern, molecular methods. Serological
      diagnosis of viral infections is used very widely in routine laboratory work.
      Besides many advantages, such as rapidity, possibility of testing many samples at
      the same time, the ability to determine classes and types of antibodies as well
      as titres, serodiagnosis has many limitations. Recently, molecular methods have
      become more and more important in laboratory diagnosis of viral diseases. These
      methods are based on detection of viral nucleide acids by hybridisation with
      specific probes or amplification of the conserved regions of viral genome by PCR.
      These tecniques are especially useful for detection of latent infections and in
      determining the success of antiviral therapy.

PMID- 18088049
TI  - [Gerhard Kuntscher and intramedullary fixation].
AB  - Gerhard Kuntscher, a German surgeon, was born in Zwickau in 1900. He graduated
      from the School of Medicine in Jena in 1926. He is renowned for the development
      of intramedullary fixation as a solution for fixation of fractures in the long
      bones. He worked in the Freiburg and Hamburg hospitals, but gained most
      experience during the Second World War, when he was on the Eastern front. In the
      period 1943-1944, he was the chief surgeon in the German military hospital in
      Kemio (Finland). After the war, he worked in hospitals is Schleswig and Hamburg
      until his retirement in 1965. He introduced the method of percutaneous
      intramedullary nailing in the femur fractures, as well as the interlocking nail,
      nail fixation of the pertrochanteric fractures and nails for intramedullary
      osteotomy. He published over 200 papers and 4 books. In his papers, he was often
      ahead of his time, and today is considered one of the founders of the concept of
      intramedullary fixation in fractures.

PMID- 18088050
TI  - [Ancient Greek in modern language of medicine].
AB  - In order to standardize language of medicine, it is essential to have a good
      command of ancient Greek and Latin. We cannot deny a huge impact of ancient Greek
      medicine on medical terminology. Compounds of Greek origin related to terms for
      organs, illnesses, inflammations, surgical procedures etc. have been listed as
      examples. They contain Greek prefixes and suffixes transcribed into Latin and
      they have been analysed. It may be concluded that the modern language of medicine
      basically represents the ancient Greek language transcribed into Latin.

PMID- 18088052
TI  - Are E. coli the culprit?

PMID- 18088051
TI  - Effects of the opioid analgesic oxymorphone hydrochloride on reproductive
      function in male and female rats.
AB  - BACKGROUND: Endogenous opioids seem to regulate hypothalamic gonadotropin release
      in both males and females, as evidenced by the effects of opioid agonists and
      antagonists on LHRH release and reproductive hormone levels. The effects of long
      term oral administration of opioid analgesics on reproductive function have not
      been well characterized. METHODS: The reproductive effects of oxymorphone, a
      potent opioid agonist, were investigated in male and female Crl:CD(SD) IGS BR
      rats at oral doses of 0, 5, 10, and 25 mg/kg/day (25 animals/sex/group). Males
      were treated for approximately 9 weeks (mated after 4 weeks of dosing). Females
      were treated for 14 days before mating, and through Gestation Day (GD) 7. Estrous
      cycling was evaluated during the premating period. On GD15, pregnancy status and
      the numbers of corpora lutea, implantation sites, live and dead embryos were
      determined. Epididymal and testicular sperm counts and epididymal sperm motility
      and morphology were evaluated in males. RESULTS: Two males given 25 mg/kg/day
      died. Behavioral changes and deficits in body weight gain occurred at all doses.
      There were no effects of oxymorphone on reproductive function or sperm parameters
      in males. The estrous cycle was prolonged in females given 25 mg/kg/day (mean of
      5.3 vs. 4.3 days in controls). A small, but consistent decrease in the numbers of
      corpora lutea (with associated decreases in implantation sites and embryos)
      occurred in females given > or =10 mg/kg/day. There were no effects on mating or
      fertility in females. CONCLUSIONS: Oxymorphone seems to partially inhibit
      ovulation in female rats, with no significant effects on male reproductive
      outcome.

PMID- 18088054
TI  - Long-term effect of varicocele repair on intratesticular arterial resistance
      index.
AB  - PURPOSE: To investigate the long-term effect of varicocele repair on ipsilateral
      intratesticular arterial resistance index (RI) using color Doppler sonography
      (CDS). METHODS: A total of 26 infertile patients with left varicocele who
      underwent a testicular artery and lymphatic-sparing subinguinal varicocelectomy
      were examined with CDS for intratesticular flow parameters before and at least 6
      months after surgery. We also evaluated preoperative and postoperative semen
      parameters. RESULTS: The mean values of RI, end-diastolic velocity and
      pulsatility index decreased significantly after surgery, whereas no significant
      change was observed in peak systolic velocity. Repair of the varicocele resulted
      in a statistically significant increase in the total sperm count, motility,
      morphology, and total motile sperm count. However, no significant correlation was
      found between sperm parameters and RI values (p > 0.05). CONCLUSIONS: Our data
      show that a significant improvement occurs in testicular blood supply and sperm
      parameters after surgical varicocele repair, without significant correlation
      between these 2 changes.

PMID- 18088053
TI  - Autophagy gene ATG16L1 influences susceptibility and disease location but not
      childhood-onset in Crohn's disease in Northern Europe.
AB  - BACKGROUND: The rs2241880A/G variant of the ATG16L1 gene has been associated with
      susceptibility to ileal Crohn's disease (CD) in adults. Our aim was to assess
      whether germline variation of ATG16L1 acts as an independent determinant of
      susceptibility to childhood-onset CD in the high-incidence Scottish population.
      METHODS: In all, 2195 subjects (361 children (inflammatory bowel disease [IBD]
      diagnosis <17 years), their parents (n = 634), 855 adult IBD patients, and 345
      controls were genotyped. Case-control analysis was powered to detect effect sizes
      with an odds ratio (OR) >1.39 in pediatric CD. Case-control analysis,
      transmission disequilibrium testing (TDT), analysis of variance (ANOVA) of growth
      parameter z-scores, Kruskal-Wallis test (age at diagnosis), and multifactorial
      genotype-phenotype analysis (Montreal classification) were performed. 7.8% of
      pediatric CD patients and 37.2% of adult CD patients had pure ileal disease.
      RESULTS: We confirmed the association of the rs2241880G-allele with adult-onset
      CD (60.7% versus controls 53.9%, P = 0.01, OR 1.32, 95% confidence interval [CI]
      1.07-1.63) in contrast to childhood-onset CD (54.1% versus controls, P = 0.95, OR
      1.01, 95% CI 0.80-1.26). TDT analysis was negative. Genotype-phenotype analysis
      demonstrated an association of pure ileal disease with the rs2241880G-allele (P =
      0.02, OR 1.34, 95% CI 1.03-1.74). Using binary logistic regression analysis we
      confirmed the effect of rs2241880 genotype (GG) on ileal disease versus colonic
      disease (P = 0.03, OR 2.43, 95% CI 1.05-5.65). ATG16L1 genotype did not influence
      age at CD diagnosis. ANOVA of z-scores of height, weight, and body mass index
      (BMI) at CD diagnosis in children showed no association with genotype.
      CONCLUSIONS: The ATG16L1 variant is associated with susceptibility to adult CD in
      Scotland, but not early-onset disease. These contrasting effects are primarily
      driven by differences in disease location between early-onset and adult-onset
      disease.

PMID- 18088055
TI  - Effect of preload reduction on sonographic myocardial integrated backscatter.
AB  - PURPOSE: Sonographic myocardial tissue characterization with integrated
      backscatter (IBS) is affected by both structural and functional properties of the
      myocardium. The aim of the present study was to investigate the effect of preload
      reduction by hemodialysis (HD) on IBS measurements. METHODS: Fifty-two patients
      on maintenance HD underwent echocardiography before and after a routine HD
      session. Measurements included the variation of IBS during the cardiac cycle (CV
      IBS) and calibrated IBS (cal-IBS). RESULTS: After HD, there were significant
      reductions in left ventricular end-diastolic and end-systolic dimensions and left
      atrial diameter. There was a reduction in stroke volume and LV ejection fraction
      consistent with a reduction in preload. Furthermore, CV-IBS was significantly
      lower after HD (7.9 +/- 2.2 versus 6.9 +/- 1.8 dB, 7.0 +/- 2.1 versus 6.2 +/- 1.9
      dB, and 9.0 +/- 2.6 versus 8.1 +/- 2.0 dB [p < 0.01], respectively, in the left
      anterior, lateral, and inferior wall of the ventricle). Cal-IBS remained
      unchanged after dialysis compared with baseline. CV-IBS and ultrafiltration
      volume were significantly correlated. CONCLUSION: HD leads to a decrease in CV
      IBS that appears to be preload-dependent. This finding is in concordance with
      diminished left ventricular performance during HD.

PMID- 18088056
TI  - Contrast-enhanced sonography in the diagnosis of small hepatocellular carcinoma <
      or =2 cm.
AB  - PURPOSE: To evaluate the usefulness of contrast-enhanced sonography (CEUS) in the
      diagnosis of small hepatocellular carcinoma (HCC) measuring < or =2 cm in
      diameter. METHODS: We identified 104 focal liver lesions measuring < or =2 cm in
      104 consecutive patients who were enrolled for baseline sonography (BUS) and CEUS
      examination (49 HCCs, 55 non-HCCs). A real-time, contrast-specific mode of
      contrast pulse sequencing and a sulphur hexafluoride-filled microbubble contrast
      agent were used for CEUS. The diagnostic performances of BUS and CEUS in
      differentiating focal liver lesions (HCC or non-HCC) were analyzed and compared.
      RESULTS: On CEUS, 43 (87.8%) of the 49 HCC lesions were hyperenhanced, 5 (10.2%)
      were isoenhanced, and 1 (2%) was hypoenhanced during the arterial phase when
      compared with adjacent liver tissue. Thirty-nine (79.6%) HCCs exhibited washout
      from the portal phase to the late phase. The sensitivity, specificity, positive
      predictive value, negative predictive value, and overall accuracy before and
      after contrast agent administration were 28.6% (14/49) versus 79.6% (39/49) (p <
      0.001), 94.5% (52/55) versus 92.7% (51/55) (p > 0.05), 82.4% (14/17) versus 90.7%
      (39/43) (p > 0.05), 59.8% (52/87) versus 90.7% (39/43) (p < 0.01), and 63.5%
      (66/104) versus 86.5% (90/104) (p < 0.001), respectively. No significant
      difference in diagnostic performance of CEUS was found between lesions measuring
      < or =1.5 cm and those 1.6-2 cm and between lesions located at a depth of < or =6
      cm from the skin and those located deeper. CONCLUSIONS: CEUS significantly
      improved the diagnostic performance in characterization of small HCCs < or =2 cm
      compared with BUS.

PMID- 18088057
TI  - The role of Doppler sonography in predicting severity of acute pancreatitis.
AB  - PURPOSE: To investigate the role of Doppler sonography (DUS) examination of major
      abdominal arteries in predicting severity of acute pancreatitis (AP). METHODS:
      Twenty-nine patients diagnosed with AP and 14 controls were blindly and
      prospectively evaluated with Doppler sonography. Disease severity was defined
      clinically according to acute physiology and chronic health evaluation (APACHE
      II) score and was classified as severe for APACHE II score > or =8. DUS
      examination included the measurement of peak systolic velocity (PSV), end
      diastolic velocity (EDV), pulsatility index (PI), and resistance index (RI) of
      the celiac artery (CA) and superior mesenteric artery (SMA). Statistical analysis
      included Mann-Whitney U test, Student t test, and receiver operating
      characteristic curve analysis. RESULTS: Twelve patients had severe AP and 17 had
      mild AP. PSV, EDV, and PI of the CA and RI of the SMA were higher in the severe
      AP group than in the mild AP and control groups (p < 0.001 and p < 0.0001,
      respectively). The sensitivity and specificity were 100% and 94%, respectively,
      for a 87 cm/second CA PSV cutoff value, 75% and 100%, respectively, for a 22
      cm/second CA EDV cutoff value, 92% and 82%, respectively, for a 1.29 CA PI cutoff
      value, and 100% and 100%, respectively, for a 0.86 SMA RI cutoff value.
      CONCLUSION: DUS can be useful in predicting the severity of AP in the early
      period of admission phase of the disease.

PMID- 18088058
TI  - Sonographically guided excisional biopsy of small abdominal wall masses using
      vacuum-assisted biopsy device.
AB  - We report the case of a 37-year-old man who underwent excision of small benign
      abdominal wall masses using a vacuum-assisted biopsy device designed for breast
      biopsy (Mammotome). To our knowledge, this is the first application of such a
      device to remove a soft tissue mass other than a breast lesion.

PMID- 18088059
TI  - Decrease in DEET repellency caused by nitric oxide in Rhodnius prolixus.
AB  - N,N-diethyl-3-methylbenzamide (DEET) is widely used as an insect repellent;
      however, little is known about its mode of action. On the other hand, nitric
      oxide (NO) participates in the olfaction transduction pathway of insects. In this
      work, nitroso-acetyl-cysteine (SNAC), a nitric oxide donor, or dibutyril-cyclic
      GMP (db-cGMP), the cyclic nucleotide analog, were applied on fifth instar nymphs
      of Rhodnius prolixus before exposing them to DEET, to obtain information about
      the possible role of NO/cGMP system in the olfaction process. In the first place,
      we exposed the nymphs to several DEET concentrations (70, 700, 1,750, and 3,500
      microg/cm2). All these concentrations produced a repellent effect. A decrease in
      repellency during the course of the experiment was observed when the nymphs were
      exposed to high concentrations of DEET (700 and 1,750 microg/cm2), suggesting an
      adaptation phenomenon. The pre-treatment of the insects with 15 microg /insect of
      SNAC or 2 microg/insect of db-cGMP produced a reduction of the repellency. An
      increase in locomotor activity was observed in insects exposed to 350 or 700
      microg/cm2 DEET. Although exposure to 70 microg/cm2 DEET produced a high
      repellency response, it did not modify the insects' locomotor activity. Insects
      treated with two doses of SNAC before being exposed to 350 microg/cm2 of DEET
      showed no differences in locomotor activity compared to controls.

PMID- 18088060
TI  - In vivo measurement of nicotinic acetylcholine receptors with [18F]norchloro
      fluoro-homoepibatidine.
AB  - Functional changes of nicotinic acetylcholine receptors (nAChR) are important
      during age-related neuronal degeneration. Recent studies demonstrate the
      applicability of the nAChR ligand 2-[(18)F]F-A-85380 for neuroimaging of patients
      with dementias. However, its binding kinetics demands a 7-h acquisition time
      limiting its practicality for clinical PET studies. Thus, the authors developed
      [(18)F]norchloro-fluoro-homoepibatidine ([(18)F]NCFHEB) for nAChR imaging. The
      kinetics of the two enantiomers of [(18)F]NCFHEB were compared with 2-[(18)F]F
      A85380 in porcine brain to evaluate their potential for human neuroimaging.
      Twenty-four juvenile female pigs were studied with PET using [(18)F]NCFHEB. Nine
      animals received an additional i.v. injection (1 mg/kg) of the nAChR agonist
      A81418 before radiotracer administration followed by infusion (2 mg/kg/7h)
      thereafter. Several compartment models were applied for quantification. (-)- and
      (+)-[(18)F]NCFHEB showed a twofold to threefold higher brain uptake than 2
      [(18)F]F-A-85380. All three radiotracers displayed spatially heterogeneous
      binding kinetics in regions with high, moderate, or low specific binding. The
      equilibrium of specific binding of (-)-[(18)F]NCFHEB was reached earlier than
      that of (+)-[(18)F]NCFHEB or 2-[(18)F]F-A85380. Continuous administration of the
      nAChR agonist A81418 inhibited the specific binding of (-)- and (+)-[(18)F]NCFHEB
      but not of 2-[(18)F]F-A85380. The peripheral metabolism of (+)-[(18)F]NCFHEB
      proceeded somewhat slower than that of the other radiotracers. Both enantiomers
      of [(18)F]NCFHEB are appropriate radiotracers for neuroimaging of nAChR in pigs.
      Their binding profile in vivo appears to be more selective than that of 2
      [(18)F]F-A85380. (-)-[(18)F]NCFHEB offers a faster equilibrium of specific
      binding than 2-[(18)F]F-A85380.

PMID- 18088061
TI  - Behavioral responding and nucleus accumbens cell firing are unaltered following
      periods of abstinence from sucrose.
AB  - A critical feature of cocaine addiction is the strong propensity to relapse
      following periods of abstinence. Here, we examined whether abstinence from
      sucrose self-administration in rats altered behavioral responding and nucleus
      accumbens (NAc) cell firing in a manner similar to that observed following
      cocaine abstinence. Rats (n = 22) were trained to self-administer sucrose on a
      short-access schedule, previously shown to increase motivated behavior following
      sucrose abstinence, and then underwent either a 0, 7, or 30 day period of
      abstinence. Next, electrophysiological recording procedures were used to examine
      NAc activity (n = 199 neurons) during resumption of sucrose self-administration.
      Results showed no increase in sucrose-seeking or changes in cell firing of NAc
      neurons following any abstinence period. Furthermore, in a separate group of
      animals (n = 17) trained under identical conditions, sucrose-seeking behaviors
      were assessed during extinction and cue-induced reinstatement to further examine
      if any changes in motivated responding are evident following abstinence. Again,
      no evidence was obtained for any alterations in sucrose-seeking across abstinence
      conditions. These results suggest that natural rewards, such as sucrose, when
      provided in short access, do not always elicit robust changes in motivated
      responding, or NAc cell firing following abstinence unlike that observed in prior
      studies with cocaine. These findings are discussed with respect to the role of
      the NAc in processing goal-directed behaviors for drug vs. natural rewards
      following periods of abstinence.

PMID- 18088062
TI  - Stress-induced synaptic changes in the rat anterior cingulate cortex are
      dependent on endocrine developmental time windows.
AB  - Fetal and neonatal brain development is characterized by developmental time
      windows during which brain regions or neuron types are specifically sensitive to
      environmental influences. Previous studies on cortical development have revealed
      evidence for the hypothesis that the extent and the direction of experience
      induced neuronal and synaptic changes correlate with time windows of endocrine
      development. To further test this hypothesis we exposed rats to neonatal
      separation stress during different phases of endocrine maturation, i.e. prior,
      during and after the stress hyporesponsive period (SHRP) of the hypothalamic
      pituitary-adrenal (HPA) axis. We show here that only stress during the SHRP
      resulted in significantly decreased (-29%) spines densities on the basal
      dendrites of pyramidal cells in layer V of the anterior cingulate cortex (ACd),
      whereas stress during the other two tested time windows had no effect on these
      parameters. Dendritic length remained unaffected by stress exposure at any of the
      tested time windows. These results reveal specific developmental time window for
      synaptic wiring within the deeper layers of the anterior cingulate cortex, which
      seem not to be mediated by hormonally induced mechanisms.

PMID- 18088063
TI  - Viewpoint: Discriminating between noncompetitive and allosteric interactions.
AB  - Understanding inhibition modes other than competitive is of clear importance in
      neuropharmacology. However, there appears to be some confusion concerning modes
      of inhibition that are not of the competitive type. It is critical to make a
      distinction between "not competitive" and "noncompetitive," as the later is a
      particular mode of inhibition. Further, there appears to be confusion between
      noncompetitive and allosteric behavior. Our purpose in this contribution is to
      explore the basis of these terms so that insight into pharmacological systems has
      a firmer mechanistic basis.

PMID- 18088064
TI  - Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD):
      upregulated colonic IL-17F expression in active Crohn's disease and analysis of
      the IL17F p.His161Arg polymorphism in IBD.
AB  - BACKGROUND: Interleukin (IL)-17F, produced in IL-23R-expressing Th17 cells, is a
      novel member of the IL-17 cytokine family. Given the association of IL23R with
      inflammatory bowel disease (IBD), we characterized the role of IL-17F in IBD
      including its intestinal gene expression and the effect of the IL17F p.His161Arg
      polymorphism on disease susceptibility and phenotype of Crohn's disease (CD) and
      ulcerative colitis (UC). In addition, we analyzed the IL17F p.His161Arg
      polymorphism for potential epistasis with IL23R and NOD2/CARD15 variants.
      METHODS: Intestinal IL-17F mRNA expression was measured by quantitative
      polymerase chain reaction (PCR). Genomic DNA from 1682 individuals (CD: n = 499;
      UC: n = 216; controls: n = 967) was analyzed for the presence of the IL17F
      p.His161Arg polymorphism, the 3 NOD2 variants, p.Arg702Trp, p.Gly908Arg, and
      p.Leu1007fsX1008, and 10 CD-associated IL23R variants. RESULTS: Intestinal IL-17F
      mRNA expression was 4.4-fold increased in inflamed colonic lesions compared to
      uninflamed biopsies in CD (P = 0.016) but not in UC. However, the mean intestinal
      IL-17F mRNA expression was higher in UC than in CD (P < 0.0001). The IL17F
      p.His161Arg substitution was observed with similar frequencies in IBD patients
      and controls and was not associated with a certain disease phenotype, but weakly
      associated with a low body mass index (BMI; P = 0.009) and an earlier age of
      disease onset (P = 0.039) in UC. There was no evidence for epistasis between the
      IL17F p.His161Arg polymorphism and IBD-associated single nucleotide polymorphisms
      within the IL23R gene. CONCLUSIONS: Intestinal IL17F gene expression is increased
      in active CD. The IL17F p.His161Arg polymorphism is not associated with IBD
      susceptibility and has no epistatic interaction with CD-associated IL23R
      variants.

PMID- 18088065
TI  - Retroviral-based gene therapy with cyclooxygenase-2 promotes the union of bony
      callus tissues and accelerates fracture healing in the rat.
AB  - BACKGROUND: An in vivo gene therapy strategy was developed to accelerate bone
      fracture repair. METHODS: Direct injection of a murine leukemia virus-based
      vector targeted transgene expression to the proliferating periosteal cells
      arising shortly after fracture. Cyclooxygenase-2 (Cox-2) was selected because the
      transgene for its prostaglandin products that promote angiogenesis, bone
      formation and bone resorption, are all required for fracture healing. The human
      (h) Cox-2 transgene was modified to remove AU-rich elements in the 3'
      untranslated region and to improve protein translation. RESULTS: In vitro studies
      revealed robust and sustained Cox-2 protein expression, prostaglandin E(2) and
      alkaline phosphatase production in rat bone marrow stromal cells and osteoblasts
      transgenic for the hCox-2 gene. In vivo studies in the rat femur fracture
      revealed that Cox-2 transgene expression produced bony union of the fracture by
      21 days post-fracture, a time when cartilage persisted within the fracture
      tissues of control animals and approximately 1 week earlier than the healing
      normally observed in this model. None of the ectopic bone formation associated
      with bone morphogenetic protein gene therapy was observed. CONCLUSIONS: This
      study represents the first demonstration that a single local application of a
      retroviral vector expressing a single osteoinductive transgene consistently
      accelerated fracture repair.

PMID- 18088066
TI  - Chiral discrimination of alpha-amino acids by DNA tetranucleotides under
      electrospray ionization conditions.
AB  - A set of DNA tetranucleotides, which are 3'- or 5'-end extended versions of GCA,
      was used as chiral selectors for the discrimination of enantiomers of alpha-amino
      acids. The [X+Y-2H](2-) ions of the 1:1 complexes were generated by
      electrospraying a mixture of tetranucleotide (X) and amino acid (Y) solution.
      Chiral discrimination was achieved by studying the collision-induced dissociation
      spectra of the [X+Y-2H](2-) ion and the ratio of relative abundance of precursor
      ion to that of the product ion was used to measure the extent of discrimination.
      Among the tetranucleotides used, GCAA and GGCA exhibited better discrimination,
      in which GCAA showed D-selectivity and GGCA showed L-selectivity for the studied
      amino acids. In addition, binding constants were measured for the 1:1 complexes
      of phenylalanine enantiomers with GCAA and GGCA. Ltd.

PMID- 18088067
TI  - Electron ionization mass spectrometric study of N-benzyl- and N-nitrobenzyl
      substituted derivatives of cytisine. II.

PMID- 18088068
TI  - On the photochemical oxidation of benzene and its relevance at environmental
      level.

PMID- 18088069
TI  - Fragmentation mechanisms in electron ionization mass spectrometry of 5-nitro- and
      8-nitroquinoline: a comparative study.

PMID- 18088070
TI  - Characterization of bovine surfactant proteins B and C by electrospray ionization
      mass spectrometry.
AB  - Bovine surfactant proteins B (SP-B) and C (SP-C) were analyzed by nano
      electrospray ionization mass spectrometry (nano-ESI-MS). The observed molecular
      masses showed discrepancies compared to the calculated molecular masses using the
      published amino acid sequences. The number of cysteine residues in the published
      bovine SP-B amino acid sequences also failed to match the observed mass shift
      upon reduction of the SP-B dimer. To determine the amino acid sequences of two
      proteins, SP-B was first digested with trypsin and analyzed by liquid
      chromatography/tandem mass spectrometry (LC/MS/MS), while SP-C was analyzed by
      MS/MS in its intact form. The amino acid sequence of bovine SP-B determined here
      matches the observed molecular mass. The sequence is almost identical to the
      sheep SP-B except for two amino acid residues, consistent with the proximity of
      the two species. The correct sequence contains seven cysteine residues. Bovine SP
      B exists as dimers and all cysteines are oxidized to form disulfide bonds in
      physiological conditions, which is in agreement with the observed mass shift upon
      reduction of the SP-B dimer. These cysteine residues are completely conserved
      across all species indicating their importance for the biological functions of
      this surfactant protein. The sequence of SP-C determined here also reveals an L
      to V substitution at its position 22 compared with the published bovine SP-B
      sequence.

PMID- 18088071
TI  - A new in vitro approach for the simultaneous determination of phase I and phase
      II enzymatic activities of human hepatocyte preparations.
AB  - Primary hepatocytes are still the best qualified in vitro system to anticipate
      drug metabolism in man. Recent advances in hepatocytes cryopreservation have
      notably increased their use not only for drug metabolism studies, but also for
      other applications such as cell transplantation. Evaluation of the drug
      metabolizing competence of each hepatocytes preparation is needed. To date, the
      metabolic characterization of hepatocytes preparations relies on the assessment
      of phase I activities and the role of phase II enzymes receives little attention.
      A novel approach for the rapid assessment of the metabolic functionality of
      hepatocytes has been developed. A five-probe cocktail was used to simultaneously
      determine the enzymatic activities of major human phase I CYPs (CYP1A2, CYP2A6,
      CYP2C9, CYP2E1, CYP3A4), as well as two phase II enzymes: glucuronidase (UGTs)
      and sulfotransferase (SULT). Liquid chromatography/tandem mass spectrometry was
      used as the technique of choice for the determination of the enzymatic activities
      in a single run. Results showed that the method described herein permits a rapid
      assessment of the metabolic capabilities of human hepatocyte preparations as well
      as an estimation of the quality of freshly isolated or cryopreserved hepatocytes.

PMID- 18088072
TI  - How are Azathioprine and 6-mercaptopurine dosed by gastroenterologists? Results
      of a survey of clinical practice.
AB  - BACKGROUND: Azathioprine (AZA) and 6-mercaptopurine (6-MP) are accepted as
      effective therapy for Crohn's disease and ulcerative colitis. Although general
      guidelines have been suggested for weight-based dosing of thiopurines, no
      standard of care has been established. Clinical trials have demonstrated efficacy
      for weight-based dosing of AZA at 2.5 mg/kg/day and 6-MP at 1.5 mg/kg/day.
      Escalation of dosing is recommended within 2 weeks of initiating therapy. The aim
      was to determine the prescribing practices of community practice
      gastroenterologists with respect to 6-MP/AZA dosing. METHODS: Questionnaires were
      distributed via a mail database or during gastroenterology society meetings to
      gastroenterologists in NY, NJ, and CT. Questionnaires ascertained starting doses
      of AZA/6-MP, use of thiopurine methyltransferase (TPMT) enzyme testing, and
      strategy for dose optimization. RESULTS: A total of 145 questionnaires were
      collected. Twenty-four percent of gastroenterologists escalated the dose within 2
      weeks after initiating therapy. The majority used weight-based dosing as their
      target of therapy. Thirty-five percent reported measuring TPMT levels and 46%
      used metabolite monitoring. CONCLUSIONS: Most gastroenterologists take longer
      than recommended to raise the dose of AZA/6-MP. Although the majority of
      gastroenterologists reported maximal dosages based on weight, there may be a
      delay in achieving this goal. Optimizing dosing of AZA/6-MP may improve efficacy
      and reduce the need to use additional therapy.

PMID- 18088073
TI  - Development of a Korean version of the behavior rating scale for dementia (BRSD
      K).
AB  - OBJECTIVE: The purpose of this study was to develop a Korean version of the
      behavior rating scale for dementia (BRSD-K) for evaluating behavioral and
      psychological symptoms of dementia. METHODS: The BRSD-K was administered to the
      informants of 268 subjects with dementia. Internal, inter-rater and test-retest
      reliabilities were tested. To evaluate construct validity, exploratory factor
      analysis was performed. To evaluate concurrent validity, Pearson correlation
      coefficients between BRSD-K scores and the corresponding scores of the Korean
      version of the neuropsychiatric inventory (NPI-K) were calculated. RESULTS: BRSD
      K demonstrated substantially high levels of reliabilities. Factor analysis
      identified seven factors, i.e. depressive symptoms, irritability/aggression,
      psychotic symptoms, behavioral dysregulations, sleep disturbance, inertia, and
      appetite. Correlations between BRSD-K and corresponding NPI-K scores were
      statistically significant (p < 0.05). CONCLUSIONS: BRSD-K was found to be a
      reliable and valid instrument for evaluating BPSD.

PMID- 18088075
TI  - Globalization: the key challenge facing health economics in the 21st century.

PMID- 18088077
TI  - How hypoglycaemia can affect the life of a person with diabetes.
AB  - Hypoglycaemia is the commonest side-effect of insulin treatment for diabetes, and
      is the single greatest barrier to achieving and maintaining good glycaemic
      control. Severe hypoglycaemia (requiring assistance for recovery) is associated
      with significant morbidity and is feared by most people with type 1 diabetes and
      their families. It causes stress and anxiety and may influence self-management
      and glycaemic control. The annual prevalence of severe hypoglycaemia is around
      30% in people with type 1 diabetes, and is higher in those with risk factors such
      as strict glycaemic control, impaired awareness of hypoglycaemia and increasing
      duration of diabetes. It is also common during sleep (nocturnal hypoglycaemia).
      Neurological manifestations include coma, convulsions, transient hemiparesis and
      stroke, while reduced consciousness and cognitive dysfunction may cause accidents
      and injuries. Cardiac events may be precipitated such as arrhythmias, myocardial
      ischaemia and cardiac failure. Hypoglycaemia can affect all aspects of life,
      including employment, driving, recreational activities involving exercise, and
      travel, and measures should be taken in all of these situations to avoid this
      potentially dangerous side-effect of insulin therapy.

PMID- 18088078
TI  - Evaluation of gliclazide ability to attenuate the hyperglycaemic 'memory' induced
      by high glucose in isolated human endothelial cells.
AB  - BACKGROUND: Patients with long-term exposure to high levels of hyperglycaemia
      remain more susceptible to diabetes-related complications, even with subsequent
      lower levels of hyperglycaemia. We sought to confirm the hypothesis that exposure
      to continuous increased glucose results in a memory of cellular stress in
      isolated endothelial cells, even when switched back to normal glucose, and to
      investigate the ability of gliclazide to attenuate this phenomenon. METHODS:
      Human umbilical vein endothelial cells were incubated for 21 days in normal
      glucose (5 mmol/L), high glucose (30 mmol/L), or high glucose for 14 days
      followed by normal glucose for 7 days (memory condition). The effects of
      gliclazide (10 micromol/L) and glibenclamide (1 micromol/L) were evaluated in the
      memory condition and added to the culture media early (first 14 days), late (last
      7 days), or throughout the study. Oxidative stress and cell apoptosis parameters
      were investigated. RESULTS: Continuous high glucose increased reactive oxygen
      species, 8-OHdG, nitrotyrosine, caspase-3, and reduced Bcl-2 expression. These
      deleterious effects were also observed in the memory condition. Gliclazide
      applied early or throughout the study improved all parameters. In contrast,
      glibenclamide showed no relevant effect on study parameters. CONCLUSIONS: Our
      results suggest that gliclazide prevents endothelial cell apoptosis by reducing
      oxidative stress. The results appear to confirm the hypothesis that exposure of
      cells to continuous increased glucose results in a hyperglycaemic cellular memory
      that remains, even when cells are switched back to normal glucose. Gliclazide
      attenuated this cellular memory, decreasing oxidative stress and protecting
      vascular endothelial cells from apoptosis.

PMID- 18088076
TI  - Randomized double-blind placebo-controlled donepezil augmentation in
      antidepressant-treated elderly patients with depression and cognitive impairment:
      a pilot study.
AB  - OBJECTIVE: To assess combined antidepressant and cognitive enhancer treatment in
      elderly patients presenting with depression plus cognitive impairment. METHODS:
      Twenty-three elderly (>50 years old) depressed, cognitively impaired (DEP-CI)
      patients participated in a pilot study. We evaluated whether, after 8 weeks of
      open antidepressant treatment, donepezil HCl (Aricept) would afford added
      cognitive benefit compared to placebo in a randomized 12-week trial. A subsample
      continued in an 8-month extension phase of open treatment with donepezil.
      Neuropsychological testing (NPT) was performed and antidepressant response
      monitored at baseline and the 8, 20, and 52-week time points. RESULTS: At 8
      weeks, the antidepressant response rate was 61% (14/23). Improvement in SRT
      immediate recall (SRT-IR; e.g. episodic verbal memory) was observed in responders
      compared to non-responders. During the 12-week, placebo-controlled, donepezil add
      on trial, patients on donepezil showed further improvement in SRT-IR versus
      patients on placebo. In the open extension phase, patients who continued open
      donepezil treatment (n = 6) maintained improvement in memory and tended to show
      an advantage over patients who never received donepezil and were evaluated at the
      52-week time point (n = 6). There were no observed significant donepezil effects
      on non-memory cognitive domains. CONCLUSION: These preliminary findings suggest
      that addition of a cholinesterase inhibitor (AChEI) following antidepressant
      medication treatment in elderly Dep-CI patients may improve cognition, and
      support the need for a confirmatory, larger randomized placebo-controlled trial.

PMID- 18088079
TI  - Proinsulin C-peptide abrogates type-1 diabetes-induced increase of renal
      endothelial nitric oxide synthase in rats.
AB  - BACKGROUND: Proinsulin C-peptide shows ameliorative effects on diabetic
      complications, possibly through the production of nitric oxide (NO). On the
      contrary, increased local availability of NO and expression of endothelial NO
      synthase (eNOS) in the renal endothelium are shown to be involved in the
      progression of diabetic nephropathy. The aim of this study was to elucidate the
      effect of C-peptide and insulin as a reference on the eNOS expression in the
      early phase of type 1 diabetic rat kidney. METHODS: Type 1 diabetes in rats was
      produced by streptozotocin injection and some of the rats were treated with
      either C-peptide or insulin by the aid of an osmotic pump for 1 week.
      Conventional biochemical and histological analyses were performed on tissue
      samples. RESULTS: The diabetic rats showed hyperglycemia with over 90% reduction
      of endogenous insulin and C-peptide. Replacement with C-peptide or insulin
      resulted in recovery of weight lost, but only insulin infusion lowered plasma
      glucose concentration. The eNOS protein was localized in glomeruli and
      endothelial cells of arterioles, and its amounts in the kidneys, but not in the
      lungs, of diabetic rats was increased. Replacement with C-peptide or insulin
      abrogated diabetes-induced increase of renal eNOS protein. CONCLUSION: The
      results indicate that C-peptide suppresses diabetes-induced abnormal renal eNOS
      expression, by which C-peptide may exert beneficial effects on diabetic
      nephropathy.

PMID- 18088080
TI  - Neuroendocrine pathways in benzodiazepine dependence: new targets for research
      and therapy.
AB  - Benzodiazepines are known to modulate the activity of the hypothalamo-pituitary
      adrenocortical (HPA) axis by antagonizing the effects of corticotropin-releasing
      factor (CRH). Besides regulating the HPA axis CRH evolves properties of a
      neurotransmitter in the limbic system that is closely involved in the delivery of
      the emotional consequences of the stress response. At a superordinated level
      Neuropeptide Y (NPY) and Cholecystokinin (CCK) affect the release of CRH and
      modulate thereby the intensity of the physiological stress response.
      Benzodiazepine treatment interferes not only with the release of CRH but also
      with the release of NPY and CCK. Alterations in the intracortical ratio of NPY,
      CCK and CRH are correlated with behavioural changes like increased respectively
      decreased anxiety and subsequent alterations in the activity of the HPA axis.
      Recent research offers the possibility that the alterations of plasma levels of
      these neuropeptides are not only a secondary phenomenon due to drug intake, but
      that low levels of those neuropeptides that modulate anxiety and fear can
      possibly explain addiction to substances that counterbalance these deficits.
      Depending on the available results possible implications of NPY and CCK on
      benzodiazepine addiction and withdrawal symptoms are reviewed, thereby providing
      topics for further research.

PMID- 18088081
TI  - Moderate hypoglycaemia after learning does not affect memory consolidation and
      brain activation during recognition in non-diabetic adults.
AB  - INTRODUCTION: Some aspects of memory performance are impaired during acute
      hypoglycaemia. The hippocampus is critical to formation of long-term memory, and
      may be particularly sensitive to hypoglycaemia. This study examined whether
      moderate hypoglycaemia occurring after learning would disrupt the consolidation
      process, and used functional magnetic resonance imaging (fMRI) to identify
      accompanying changes in brain activation. METHODS: Sixteen non-diabetic subjects
      each underwent two glucose clamp studies. During euglycaemia (4.5 mmol/L),
      subjects tried to memorize a series of words and a series of pictures of faces.
      Then, either hypoglycaemia (2.5 mmol/L) was induced for one hour, or euglycaemia
      was maintained. During subsequent uncontrolled euglycaemia, subjects' recognition
      of the word and face stimuli was tested, with simultaneous fMRI to measure brain
      activation during recognition. RESULTS: Face identification scores were 67.2%
      after euglycaemia and 66.9% after hypoglycaemia (p = 0.895). Word identification
      scores were 78.0 and 77.1% respectively (p = 0.701). Analysis of the fMRI
      identified two foci where activation was altered after hypoglycaemia compared
      with euglycaemia, but these were not in regions associated with memory, and were
      probably statistical artefacts. CONCLUSIONS: One hour of hypoglycaemia at 2.5
      mmol/L induced 20-40 min after learning did not disrupt memory consolidation.
      fMRI did not show evidence of altered brain activation after hypoglycaemia.
      Consolidation may be relatively resistant to hypoglycaemia, or may have been
      complete before hypoglycaemia was induced. The study was powered to detect a
      large effect, and provides some reassurance that moderate hypoglycaemia does not
      cause major disruption of previously learned memories in people with insulin
      treated diabetes.

PMID- 18088082
TI  - Substituent effects of the N,N-dimethyl- sulfamoyl group on the 1H and 13C NMR
      spectra of positional isomers of quinolines.
AB  - The complete 1H and 13C NMR spectral assignments of seven positional isomers of
      N,N-dimethylsulfamoylquinolines 2-8 and quinoline have been made using 1D and 2D
      NMR techniques, including COSY, HMQC and HMBC experiments. Deltadelta(H) and
      Deltadelta(C) substituent effects induced by the sulfamoyl group were determined.
      The sulfamoyl substituent affects proton and carbon chemical shifts both in the
      parent and in the fused (pyridine or benzene) ring.

PMID- 18088083
TI  - 1H, 13C and 15N NMR studies on adducts formation of rhodium(II) tetraacylates
      with some azoles in CDCl3 solution.
AB  - Adduct formations of rhodium(II) tetraacetate and tetratrifluoroacetate with some
      1H-imidazoles, oxazoles, thiazoles, 1H-pyrazoles and isoxazole have been
      investigated by the use of 1H, 13C, 15N NMR and electronic absorption
      spectroscopy (VIS) in the visible range. Azoles tend to form axial adducts
      containing rhodium(II) tetraacylates bonded via nitrogen atom. Bulky substituents
      close to the nitrogen atom prevent the Rh--N bond formation, and in several cases
      switch over the binding site to the oxygen or sulphur atoms. The (15)N adduct
      formation shift Deltadelta(15N) (Deltadelta = delta(adduct) - delta(ligand))
      varied from ca - 40 to - 70 ppm for the nitrogen atom involved in complexation,
      and of a few parts per million only, from ca - 6 to 3 ppm, for the non-bonded
      nitrogen atom within the same molecule. The Deltadelta(1H) values do not exceed
      one ppm; Deltadelta(13C) ranges from - 1 to 6 ppm. Various complexation modes
      have been proved by electronic absorption spectroscopy in the visible region
      (VIS). For comparison purposes, some adducts of pyridine, thiophene and furan
      derivatives have been measured as well. The experimental findings were compared
      with calculated chemical shifts, obtained by means of DFT B3LYP method, using 6
      311 + G(2d,p), 6-31(d)/LanL2DZ and 6-311G(d,p) basis set.

PMID- 18088084
TI  - Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor
      associated mesothelin.
AB  - Novel therapeutic agents that are safe and effective are needed for the treatment
      of pancreatic, ovarian, lung adenocarcinomas and mesotheliomas. Mesothelin is a
      glycosyl-phosphatidyl inositol (GPI)-linked membrane protein of 40 kDa over
      expressed in all pancreatic adenocarcinoma and mesothelioma, in >70% of ovarian
      adenocarcinoma, and in non-small cell lung and colorectal cancers. The biological
      functions of mesothelin are not known, although it appears to be involved in cell
      adhesion via its interaction with MUC16. We have recently developed MORAb-009, a
      mouse-human chimeric IgG1kappa monoclonal antibody with an affinity of 1.5 nM for
      human mesothelin. Here we provide evidence that MORAb-009 prevents adhesion of
      mesothelin-bearing tumor cells to MUC16 positive cells and can elicit cell
      mediated cytotoxicity on mesothelin-bearing tumor cells. Treatment that included
      MORAb-009 in combination with chemotherapy led to a marked reduction in tumor
      growth of mesothelin-expressing tumors in nude mice compared to chemotherapy or
      MORAb-009 treatment alone. No adverse effects of MORAb-009 were noted during
      toxicology studies conducted in non-human primates. The preclinical data obtained
      from our studies warrants pursuing clinical testing of MORAb-009. We have in fact
      initiated a Phase I clinical study enrolling patients with mesothelin-positive
      pancreatic, mesothelioma, non-small cell lung and ovarian cancers.

PMID- 18088085
TI  - Enzyme-directed positioning of nanoparticles on large DNA templates.
AB  - A method to position nanoparticles onto DNA with high resolution using an enzyme
      based approach is described. This provides a convenient route to assemble
      multiple nanoparticles (e.g., Au and CdSe) to specific positions with a high
      level of control and expandability to more complex assemblies. Atomic force
      microscopy is used to analyze the nanostructures, which have potential interest
      for biosensor, optical waveguide, molecular electronics, and energy transfer
      studies.

PMID- 18088086
TI  - In vivo production of scFv-displaying biopolymer beads using a self-assembly
      promoting fusion partner.
AB  - Recombinant production and, in particular, immobilization of antibody fragments
      onto carrier materials are of high interest with regard to diagnostic and
      therapeutic applications. In this study, the recombinant production of scFv
      displaying biopolymer beads intracellularly in Escherichia coli was investigated.
      An anti-beta-galactosidase scFv (single chain variable fragment of an antibody)
      was C-terminally tagged with the polymer-synthesizing enzyme PhaC from
      Cupriavidus necator by generating the respective hybrid gene. The functionality
      of the anti-beta-galactosidase scFv-PhaC fusion protein was assessed by producing
      the respective soluble fusion protein in an Escherichia coli AMEF mutant strain.
      AMEF (antibody-mediated enzyme formation) strains contain an inactive mutant beta
      galactosidase, which can be activated by binding of an anti-beta-galactosidase
      antibody. In vivo activation of AMEF beta-galactosidase indicated that the scFv
      is functional with the C-terminal fusion partner PhaC. It was further
      demonstrated that polymer biosynthesis and bead formation were mediated by the
      scFv-PhaC fusion protein in the cytoplasm of recombinant E. coli when the polymer
      precursor was metabolically provided. This suggested that the C-terminal fusion
      partner PhaC acts as a functional insolubility partner, providing a natural cross
      link to the bead and leading to in vivo immobilization of the scFv.
      Overproduction of the fusion protein at the polymer bead surface was confirmed by
      SDS-PAGE and MALDI-TOF/MS analysis of purified beads. Antigen binding
      functionality and specificity of the beads was assessed by analyzing the binding
      of beta-galactosidase to scFv-displaying beads and subsequently eluting the bound
      protein at pH 2.7. A strong enrichment of beta-galactosidase suggested the
      functional display of scFv at the bead surface as well as the applicability of
      these beads for antigen purification. Binding of beta-galactosidase to the scFv
      displaying beads was quantitatively analyzed by enzyme-linked assays measuring
      beta-galactosidase activity. These indicated that the anti-beta-galactosidase
      scFv-displaying beads bound a maximum of 38 ng of beta-galactosidase per 1 microg
      of bead protein, showing an apparent equilibrium dissociation constant ( KD) of
      12 x 10 (-7) M. This study clearly demonstrated that anti-beta-galactosidase scFv
      displaying polymer beads can be produced in engineered E. coli in a one-step
      process by using PhaC as a self-assembly-promoting fusion partner.

PMID- 18088087
TI  - Phosphoproteome of resting human platelets.
AB  - Beside their main physiological function in hemostasis, platelets are also highly
      involved in pathological processes, such as atherothrombosis and inflammation.
      During hemostasis, binding of adhesive substrates to tyrosine-kinase-linked
      adhesion receptors and/or soluble agonists to G-protein coupled receptors leads
      to a cascade of intracellular signaling processes based on substrate
      (de)phosphorylation. The same mechanisms are involved in platelet activation at
      sites of atherosclerotic plaque rupture, contributing to vessel occlusion and
      consequently to pathologic states, such as myocardial infarction, stroke, or
      peripheral artery disease. To gain a deeper insight into platelet function, we
      analyzed the phosphoproteome of resting platelets and identified 564
      phosphorylation sites from more than 270 proteins, of which many have not been
      described in platelets before. Among those were several unknown potential protein
      kinase A (PKA) and protein kinase G (PKG) substrates. Because platelet inhibition
      is tightly regulated especially by PKA and PKG activity, these proteins may
      represent important new targets for cardiovascular research. Thus, our finding
      that GPIbalpha is phosphorylated at Ser603 in resting platelets may represent a
      novel mechanism for the regulation of one of the most important platelet receptor
      (GPIb-IX-V) mediated signaling pathways by PKA/PKG.

PMID- 18088088
TI  - Protein quantitation in 2-D gels using fluorescence with water Raman as an
      internal standard.
AB  - We have developed a method to enhance fluorescence quantification in two
      dimensional gel electrophoresis using the inherent Raman scattering of water as
      an internal standard. We demonstrate this water internal standard (WIS) method
      using quantitative comparisons of commercially available protein standards that
      were either covalently tagged or passively stained with fluorescent tags. Thus,
      WIS opens up the possibility of enhancing intra- and intergel quantitative
      comparisons.

PMID- 18088089
TI  - Design, synthesis, and biological evaluation of (E)-styrylbenzylsulfones as novel
      anticancer agents.
AB  - Cell cycle progression is regulated by cyclins and cyclin-dependent kinases,
      which are formed at specific stages of the cell cycle and regulate the G1/S and
      G2/M phase transitions, employing a series of "checkpoints" governed by
      phosphorylation of their substrates. Tumor development is associated with the
      loss of these checkpoint controls, and this provides an approach for the
      development of therapeutic agents that can specifically target tumor cells. Here,
      we describe the synthesis and SAR of a novel group of cytotoxic molecules that
      selectively induce growth arrest of normal cells in the G1 phase while inducing a
      mitotic arrest of tumor cells resulting in selective killing of tumor cell
      populations with little or no effect on normal cell viability. The broad spectrum
      of antitumor activity in vitro and xenograft models, lack of in vivo toxicity,
      and drug resistance suggest potential for use of these agents in cancer therapy.

PMID- 18088091
TI  - Two types of beta-fructofuranosidases from Aspergillus oryzae KB.
AB  - Aspergillus oryzae KB produces two types of beta-fructofuranosidases, F1 and F2.
      F1 produces 1-kestose, nystose, and fructosyl nystose from sucrose through its
      transfructosylation action. F2 hydrolyzes sucrose to glucose and fructose. N
      Terminal amino acid sequences of the purified enzymes were DYNAAPPNLST for F1 and
      YSGDLRPQ for F2. Each enzyme encoding gene was identified in the genome of
      Aspergillus oryzae. Although the KB strain showed a higher production of F2 than
      F1 in a low sucrose liquid medium, F2 production gradually decreased, whereas F1
      production increased with increasing sucrose concentration in the medium.
      Synthesis of F1 and F2 mRNAs analyzed on reverse-transcription polymerase chain
      reaction corresponded to individual enzymatic production. During liquid culture
      of the KB strain, F1 synthesizes fructooligosaccharides from sucrose through
      transfructosylation, and F2 gradually hydrolyzes it. In a highly concentrated
      sucrose medium, intake of sucrose into the KB strain was depressed by F1 through
      synthesis of transfer products, fructooligosaccharides.

PMID- 18088092
TI  - Daily variations in oligosaccharides of human milk determined by microfluidic
      chips and mass spectrometry.
AB  - Human milk is a complex biological fluid that provides not only primary
      nourishment for infants but also protection against pathogens and influences
      their metabolic, immunologic, and even cognitive development. The presence of
      oligosaccharides in remarkable abundance in human milk has been associated to
      provide diverse biological functions including directing the development of an
      infant's intestinal microflora and immune system. Recent advances in analytical
      tools offer invaluable insights in understanding the specific functions and
      health benefits these biomolecules impart to infants. Oligosaccharides in human
      milk samples obtained from five different individual donors over the course of a
      3 month lactation period were isolated and analyzed using HPLC-Chip/TOF-MS
      technology. The levels and compositions of oligosaccharides in human milk were
      investigated from five individual donors. Comparison of HPLC-Chip/TOF-MS
      oligosaccharides profiles revealed heterogeneity among multiple individuals with
      no significant variations at different stages of lactation within individual
      donors.

PMID- 18088090
TI  - Structure-activity relationships of cyclic lactam analogues of alpha-melanocyte
      stimulating hormone (alpha-MSH) targeting the human melanocortin-3 receptor.
AB  - A variety of dicarboxylic acid linkers introduced between the alpha-amino group
      of Pro(6) and the -amino group of Lys(10) of the cyclic lactam alpha-melanocyte
      stimulating hormone (alpha-MSH)-derived Pro(6)-D-Phe(7)/D-Nal(2')(7)-Arg(8)
      Trp(9)-Lys(10)-NH2 pentapeptide template lead to nanomolar range and selective
      hMC3R agonists and antagonists. Replacement of the Pro(6) residue and the
      dicarboxylic acid linker with 2,3-pyrazine-dicarboxylic acid furnished a highly
      selective nanomolar range hMC3R partial agonist (analogue 12, c[CO-2,3-pyrazine
      CO-D-Phe-Arg-Trp-Lys]-NH2, EC50 = 27 nM, 70% max cAMP) and an hMC3R antagonist
      (analogue 13, c[CO-2,3-pyrazine-CO-D-Nal(2')-Arg-Trp-Lys]-NH2, IC50 = 23 nM).
      Modeling experiments suggest that 2,3-pyrazinedicarboxylic acid stabilizes a beta
      turn-like structure with the D-Phe/D-Nal(2') residues, which explains the high
      potency of the corresponding peptides. Placement of a Nle residue in position 6
      produced a hMC3R/hMC5R antagonist (analogue 15, c[CO-(CH 2)2-CO-Nle-D-Nal(2')-Arg
      Trp-Lys]-NH2, IC50 = 12 and 17 nM, respectively), similarly to the previously
      described cyclic gamma-melanocyte-stimulating hormone (gamma-MSH)-derived
      hMC3R/hMC5R antagonists. These newly developed melanotropins will serve as
      critical biochemical tools for elucidating the full spectrum of functions
      performed by the physiologically important melanocortin-3 receptor.

PMID- 18088093
TI  - An acid-labile block copolymer of PDMAEMA and PEG as potential carrier for
      intelligent gene delivery systems.
AB  - Intelligent gene delivery systems based on physiologically triggered reversible
      shielding technology have evinced enormous interest due to their potential in
      vivo applications. In the present work, an acid-labile block copolymer consisting
      of poly(ethylene glycol) and poly(2-(dimethylamino)ethyl methacrylate) segments
      connected through a cyclic ortho ester linkage (PEG- a-PDMAEMA) was synthesized
      by atom transfer radical polymerization of DMAEMA using a PEG macroinitiator with
      an acid-cleavable end group. PEG- a-PDMAEMA condensed with plasmid DNA formed
      polyplex nanoparticles with an acid-triggered reversible PEG shield. The pH
      dependent shielding/deshielding effect of PEG chains on the polyplex particles
      were evaluated by zeta potential and size measurements. At pH 7.4, polyplexes
      generated from PEG- a-PDMAEMA exhibited smaller particle size, lower surface
      charge, reduced interaction with erythrocytes, and less cytotoxicity compared to
      PDMAEMA-derived polyplexes. At pH 5.0, zeta potential of polyplexes formed from
      PEG- a-PDMAEMA increased, leveled up after 2 h of incubation and gradual
      aggregation occurred in the presence of bovine serum albumin (BSA). In contrast,
      the stably shielded polyplexes formed by DNA and an acid-stable block copolymer,
      PEG- b-PDMAEMA, did not change in size and zeta potential in 6 h. In vitro
      transfection efficiency of the acid-labile copolymer greatly increased after 6 h
      incubation at pH 5.0, approaching the same level of PDMAEMA, whereas there was
      only slight increase in efficiency for the stable copolymer, PEG- b-PDMAEMA.

PMID- 18088094
TI  - Free-radical-mediated protein inactivation and recovery during protein
      photoencapsulation.
AB  - Photoencapsulation of protein therapeutics is very attractive for preparing
      biomolecule-loaded hydrogels for a variety of biomedical applications. However,
      detrimental effects of highly active radical species generated during
      photoencapsulation must be carefully evaluated to maintain efficient hydrogel
      cross-linking while preserving the structure and bioactivity of encapsulated
      biomolecules. Here, we examine the free-radical-mediated inactivation and
      incomplete release of proteins from photocurable hydrogels utilizing lysozyme as
      a conservative model system. Various protein photoencapsulation conditions were
      tested to determine the factors affecting lysozyme structural integrity and
      bioactivity. It was found that a portion of the lysozyme becomes conjugated to
      polymer chains at high photoinitiator concentrations and long polymerization
      times. We also found that the more hydrophilic photoinitiator Irgacure-2959 (I
      2959, 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone) causes more
      damage to lysozyme compared to the hydrophobic photoinitiator Irgacure-651 (I
      651, 2,2-dimethoxy-2-phenylacetophenone), even though I-2959 has been previously
      shown to be more cytocompatible. Furthermore, while nonacrylated PEG provides
      only limited protection from the denaturing free radicals that are present during
      hydrogel curing, acrylated PEG macromers effectively preserve lysozyme structural
      integrity and bioactivity in the presence of either photoinitiator. Overall,
      these findings indicate how photopolymerization conditions (e.g., photoinitiator
      type and concentration, UV exposure time, etc.) must be optimized to obtain a
      functional hydrogel device that can preserve protein bioactivity and provide
      maximal protein release.

PMID- 18088095
TI  - Modular biodegradable biomaterials from surfactant and polyelectrolyte mixtures.
AB  - Polymeric assemblies are used in many biomaterials applications, ranging from
      drug-bearing nanoparticles to macroscopic scaffolds. Control over their
      biodegradation rates is usually achieved through synthetic modification of their
      molecular structure. As a simpler alternative, we exploit the associative phase
      separation in mixtures of bioderived surfactants and polyelectrolytes. The gel
      fiber scaffolds are formed via phase inversion, using a homologous series of
      fatty acid salts-sodium caprate (NaC10), laurate (NaC12), and myristate (NaC14),
      and a water-soluble chitosan derivative, N-[(2-hydroxy-3
      trimethylammonium)propyl] chitosan chloride (HTCC). Their dissolution times are
      modulated through the selection of the fatty acid molecule and vary in a
      predictable manner from minutes (for NaC10-HTCC), to hours (for NaC12-HTCC), to
      days (for NaC14-HTCC). These variations are linked to differences in surfactant
      polyelectrolyte binding strength and scale with the equilibrium binding constants
      of their mixtures. These fibers were found to be both cytocompatible and cell
      adhesive using neural stem/progenitor cells, suggesting their potential for
      utility in biomedical applications.

PMID- 18088096
TI  - Stagonolides B-F, nonenolides produced by Stagonospora cirsii, a potential
      mycoherbicide of Cirsium arvense.
AB  - Stagonospora cirsii, a fungal pathogen isolated from Cirsium arvense and proposed
      as a potential mycoherbicide of this perennial noxious weed, produces phytotoxic
      metabolites in liquid and solid cultures. Recently, the main metabolite,
      stagonolide (1), with interesting phytotoxic properties, was isolated from a
      liquid culture and characterized as a new nonenolide. In the present work this
      same fungus, grown in solid culture, exhibited an increased capacity to produce
      nonenolides. Five new nonenolides, named stagonolides B-F (2-6), were isolated
      and characterized using spectroscopic methods. When tested by a leaf disk
      puncture assay at a concentration of 1 mg/mL, these compounds showed no toxicity
      to C. arvense and Sonchus arvensis, whereas stagonolide (1) was highly toxic.
      Stagonolide (1) and stagonolide C (3) were weakly toxic to Colpoda steinii, a
      protozoan, when tested at 0.05 mg/mL, with the other stagonolides nontoxic. A
      number of structure-activity relationship observations were made.

PMID- 18088097
TI  - Antileishmanial compounds from Cordia fragrantissima collected in Burma
      (Myanmar).
AB  - A methanol extract of the wood of Cordia fragrantissima, collected in Burma
      (Myanmar), was found to exhibit significant activity against Leishmania major.
      Bioassay-guided fractionation of this extract using several chromatographic
      techniques afforded three new compounds (1-3) and five known compounds (4-8). The
      structures of the new compounds were revealed on the basis of spectroscopic data
      interpretation and by X-ray crystallographic analysis. Interestingly, the new
      compounds, despite the presence of asymmetric carbons, were found to be
      racemates. The activities of the isolates from C. fragrantissima and several
      derivatives were evaluated against the promastigote forms of Leishmania major, L.
      panamensis, and L. guyanensis.

PMID- 18088098
TI  - NF-kappaB-inhibiting naphthopyrones from the Fijian echinoderm Comanthus
      parvicirrus.
AB  - The two naphthopyrones 6-methoxycomaparvin (1) and 6-methoxycomaparvin 5-methyl
      ether (2) were isolated from a bioactive methanol-soluble extract of the Fijian
      echinoderm Comanthus parvicirrus. Their structures were assigned on the basis of
      spectroscopic methods. X-ray diffraction analysis was used to confirm the
      structure of 1. Both compounds were tested for their potential to inhibit the
      activation of the transcription factor NF-kappaB, which plays an important role
      in cancer development and inflammation, and the mechanism of action of the two
      compounds was investigated. Both naphthopyrones 1 and 2 completely inhibit TNF
      alpha-induced NF-kappaB activation at a concentration of 300 microM by inhibiting
      the enzymatic activity of the kinase IKKbeta.

PMID- 18088099
TI  - Octanorcucurbitane and cucurbitane triterpenoids from the tubers of Hemsleya
      endecaphylla with HIV-1 inhibitory activity.
AB  - Two new cucurbitacins, endecaphyllacins A (1) and B (2), together with six known
      analogues (3-8), were isolated from the tubers of Hemsleya endecaphylla. The
      structures of 1 and 2 were elucidated by NMR and MS spectroscopic analysis. The
      relative stereochemistry of 1 was determined by single-crystal X-ray diffraction.
      Compound 4 (cucurbitacin B) showed potent anti-HIV-1 in C8166 cells (EC=0.09
      microg/mL) with a selectivity index of 16.7.

PMID- 18088100
TI  - Bromophenols from the marine red alga Polysiphonia urceolata with DPPH radical
      scavenging activity.
AB  - Three new (1-3) and three known (4-6) bromophenols were isolated and identified
      from the marine red alga Polysiphonia urceolata. On the basis of extensive
      analysis of spectroscopic data, the structures of these compounds were determined
      to be 7-bromo-9,10-dihydrophenanthrene-2,3,5,6-tetraol (1), 4,7-dibromo-9,10
      dihydrophenanthrene-2,3,5,6-tetraol (2), 1,8-dibromo-5,7-dihydrodibenzo[
      c,e]oxepine-2,3,9,10-tetraol (3), urceolatol (4), 3-bromo-4,5
      dihydroxybenzaldehyde (5), and 3,5-dibromo-4-hydroxybenzaldehyde (6). Each of the
      isolated compounds was evaluated for alpha,alpha-diphenyl-beta-picrylhydrazyl
      (DPPH) radical scavenging activity, and all were found to be potent, with IC50
      values ranging from 6.1 to 35.8 microM, compared to the positive control,
      butylated hydroxytoluene (BHT), with an IC50 of 83.8 microM.

PMID- 18088101
TI  - Electrochemistry-based real-time PCR on a microchip.
AB  - The development of handheld instruments for point-of-care DNA analysis can
      potentially contribute to the medical diagnostics and environmental monitoring
      for decentralized applications. In this work, we demonstrate the implementation
      of a recently developed electrochemical real-time polymerase chain reaction (ERT
      PCR) technique on a silicon-glass microchip for simultaneous DNA amplification
      and detection. This on-chip ERT-PCR process requires the extension of an
      oligonucleotide in both solution and at solid phases and intermittent
      electrochemical signal measurement in the presence of all the PCR reagents.
      Several important parameters, related to the surface passivation and
      electrochemical scanning of working electrodes, were investigated. It was found
      that the ERT-PCR's onset thermal cycle ( approximately 3-5), where the analytical
      signal begins to be distinguishable from the background, is much lower than that
      of the fluorescence-based counterparts for high template DNA situations (3 x
      10(6) copies/microL). By carefully controlling the concentrations of the
      immobilized probe and the enzyme polymerase, improvements have been made in
      obtaining a meaningful electrochemical signal using a lower initial template
      concentration. This ERT-PCR technique on a microchip platform holds significant
      promise for rapid DNA detection for point-of-care testing applications.

PMID- 18088102
TI  - Atmospheric pressure infrared MALDI imaging mass spectrometry for plant
      metabolomics.
AB  - The utility of atmospheric pressure infrared MALDI mass spectrometry (AP IR
      MALDI) was assessed for plant metabolomics studies. Tissue sections from plant
      organs, including flowers, ovaries, aggregate fruits, fruits, leaves, tubers,
      bulbs, and seeds were studied in both positive and negative ion modes. For
      leaves, single laser pulses sampled the cuticle and upper epidermal cells,
      whereas multiple pulses were demonstrated to ablate some mesophyll layers. Tandem
      mass spectra were obtained with collision-activated dissociation to aid with the
      identification of some observed ions. In the positive mode, most ions were
      produced as potassium, proton, or sometimes sodium ion adducts, whereas proton
      loss was dominant in the negative ion mode. Over 50 small metabolites and various
      lipids were detected in the spectra including, for example, 7 of the 10
      intermediates in the citric acid cycle. Key components of the glycolysis pathway
      occurring in the plant cytosol were found along with intermediates of
      phospholipid biosynthesis and reactants or products of amino acid, nucleotide,
      oligosaccharide, and flavonoid biosynthesis. AP IR-MALDI mass spectrometry was
      used to follow the fluid transport driven by transpiration and image the spatial
      distributions of several metabolites in a white lily (Lilium candidum) flower
      petal.

PMID- 18088103
TI  - Molecular imprinting at walls of silica nanotubes for TNT recognition.
AB  - This paper reports the molecular imprinting at the walls of highly uniform silica
      nanotubes for the recognition of 2,4,6-trinitrotoluene (TNT). It has been
      demonstrated that TNT templates were efficiently imprinted into the matrix of
      silica through the strong acid-base pairing interaction between TNT and 3
      aminopropyltriethoxysilane (APTS). TNT-imprinted silica nanotubes were
      synthesized by the gelation reaction between APTS and tetraethylorthosilicate
      (TEOS), selectively occurring at the porous walls of APTS-modified alumina
      membranes. The removal of the original TNT templates leaves the imprinted
      cavities with covalently anchored amine groups at the cavity walls. A high
      density of recognition sites with molecular selectivity to the TNT analyte was
      created at the wall of silica nanotubes. Furthermore, most of these recognition
      sites are situated at the inside and outside surfaces of tubular walls and in the
      proximity of the two surfaces due to the ultrathin wall thickness of only 15 nm,
      providing a better site accessibility and lower mass-transfer resistance.
      Therefore, greater capacity and faster kinetics of uptaking target species were
      achieved. The silica nanotube reported herein is an ideal form of material for
      imprinting various organic or biological molecules toward applications in
      chemical/biological sensors and bioassay.

PMID- 18088104
TI  - Structural and motional changes induced in apo-S100A1 protein by the disulfide
      formation between its Cys 85 residue and beta-mercaptoethanol.
AB  - Recently, we have shown (Goch, G., Vdovenko, S., Kozlowska, H., and Bierzynski,
      A. (2005) FEBS J. 272, 2557-2565) that the chemical modification of Cys 85
      residue of S100A1 protein by disulfide bond formation with small thiols such as
      glutathione, cysteine, or beta-mercaptoethanol (betaME) leads to a dramatic
      increase of the protein affinity for calcium. Therefore, the biological function
      of S100A1 as a calcium signal transmitter is probably regulated by the redox
      potential within the cell. Systematic, structural studies of various mixed
      disulfides of S100A1 in the apo and holo states are necessary to elucidate the
      mechanism of this phenomenon. Using NMR methods we have determined the structure
      of apo-S100A1-betaME and, on the basis of 15N nuclear magnetic relaxation data,
      we have characterized the structural dynamics of both: modified and unmodified
      molecules of apo-S100A1. The following effects of betaME modification have been
      observed: (1) Helices IV and IV' of two protein subunits are elongated by five
      residues (85-89). (2) Conformation of the calcium binding N-terminal loops is
      dramatically changed, and structural flexibility of the N-loops as well as C
      loops markedly increases. (3) The angle between helices I and IV increases by
      approximately 20 degrees and between helices IV and IV' decreases by
      approximately 35 degrees . All these observations lead to the conclusion that
      betaME modification of apo-S100A1 makes its structure more similar to that of
      holo-S100A1, so that it becomes much better adjusted for calcium coordination.

PMID- 18088105
TI  - Trajectory surface hopping study of the O(3P) + ethylene reaction dynamics.
AB  - Spin-orbit coupling (SOC) induced intersystem crossing (ISC) has long been
      believed to play a crucial role in determining the product distributions in the
      O(3P) + C2H4 reaction. In this paper, we present the first nonadiabatic dynamics
      study of the title reaction at two center-of-mass collision energies: 0.56 eV,
      which is barely above the H-atom abstraction barrier on the triplet surface, and
      3.0 eV, which is in the hyperthermal regime. The calculations were performed
      using a quasiclassical trajectory surface hopping (TSH) method with the potential
      energy surface generated on the fly at the unrestricted B3LYP/6-31G(d,p) level of
      theory. To simplify our calculations, nonadiabatic transitions were only
      considered when the singlet surface intersects the triplet surface. At the
      crossing points, Landau-Zener transition probabilities were computed assuming a
      fixed spin-orbit coupling parameter, which was taken to be 70 cm-1 in most
      calculations. Comparison with a recent crossed molecular beam experiment at 0.56
      eV collision energy shows qualitative agreement as to the primary product
      branching ratios, with the CH3 + CHO and H + CH2CHO channels accounting for over
      70% of total product formation. However, our direct dynamics TSH calculations
      overestimate ISC so that the total triplet/singlet ratio is 25:75, compared to
      the observed 43:57. Smaller values of SOC reduce ISC, resulting in better
      agreement with the experimental product relative yields; we demonstrate that
      these smaller SOC values are close to being consistent with estimates based on
      CASSCF calculations. As the collision energy increases, ISC becomes much less
      important and at 3.0 eV, the triplet to singlet branching ratio is 71:29. As a
      result, the triplet products CH2 + CH2O, H + CH2CHO and OH + C2H3 dominate over
      the singlet products CH3 + CHO, H2 + CH2CO, etc.

PMID- 18088106
TI  - Difficulties in building radiation-generated three-spin systems using spin
      labeled luminophores.
AB  - Aromatic compounds are well-known acceptors of primary radical ions that are
      formed under high-energy irradiation of nonpolar systems. Thus formed radical ion
      pairs recombine and produce magnetosensitive fluorescence, which helps study the
      short-lived radical ions. It was initially suggested that a simple introduction
      of a spin label into the original arene would allow an easy transition from two
      spin to three-spin systems, retaining the experimental techniques available for
      radical pairs. However, it turned out that spin-labeled arenes often do not
      produce magnetosensitive fluorescence in the conditions of a conventional
      radiochemical experiment. To understand the effect of the introduced spin label,
      we synthesized a series of compounds with the general structure "stable 3
      imidazoline radical-two-carbon bridge-naphthalene" as well as their diamagnetic
      analogues. By use of this set of acceptors, we determined the processes that ruin
      the observed signal and established their connection with the chemical structure
      of the compound. We found that the compounds with flexible (saturated) two-carbon
      bridges between the luminophore and the stable radical moieties exist in solution
      in folded conformation, which leads to suppression of luminescence from
      naphthalene due to efficient through-space exchange quenching of the excited
      state by the radical. Increasing the rigidity of the bridge by introducing the
      double bond drastically increases the reactivity of the extended pi-system. In
      these compounds, the energy released upon recombination is spent in radiationless
      processes of chemical transformations both at the stage of the radical ion and at
      the stage of the electronically excited molecule.

PMID- 18088107
TI  - Influence of Go-like interactions on global shapes of energy landscapes in beta
      barrel forming model proteins: inherent structure analysis and statistical
      temperature molecular dynamics simulation.
AB  - Recently, the native-centric, coarse-grained "Go-like" protein model has gained a
      renewed popularity because of its computational simplicity and successful
      description of some key aspects of folding thermodynamics and kinetics. In the
      present paper, the properties of Go-like models are investigated in terms of the
      potential energy landscape (PEL). The non-native attractions of the beta-barrel
      forming BLN model 46-mer are scaled with a parameter 0 < or = lambda < or = 1, to
      make a continuous tuning of the PEL from multi-funneled and energetically
      frustrated at lambda = 1 to a perfect funnel including only topological
      frustration at lambda = 0. The combination of the enhanced sampling of
      "statistical temperature molecular dynamics", STMD (Kim, J.; Straub, J. E.;
      Keyes, T. Phys. Rev. Lett. 2006, 97, 050601), and extensive inherent structure
      (IS) analysis, clearly demonstrates the evolution of the topography of the PEL.
      It is shown that a small amount of Go-like interactions brings about a
      significant modification in the occupation of low-lying IS by destabilizing the
      misfolding funnel into a higher energy region, strongly influencing the folding
      thermodynamics. The alteration of the PEL also induces a dramatic change in the
      folding mechanism, from a second-order-like collapse transition into a
      cooperative, first-order-like folding transition, occurring through a transient,
      intermediate state ensemble characterized by partially structured IS. The
      appearance of multiple van der Waals loops in the statistical temperature of the
      Go-like model is associated with the development of the intermediate states.

PMID- 18088108
TI  - Springs and speeds in free energy reconstruction from irreversible single
      molecule pulling experiments.
AB  - The nonequilibrium work relation allows for the calculation of equilibrium free
      energy differences between states based on the exponential average of accumulated
      work from irreversible transitions. Here, we compare two distinct approaches of
      calculating free energy surfaces from unidirectional single-molecule pulling
      experiments: the stiff spring approximation and the Hummer-Szabo method. First,
      we perform steered molecular dynamics simulations to mechanically stretch the
      model peptide deca-alanine using harmonic potentials with different spring
      stiffnesses and at various constant pulling velocities. We then calculate free
      energy surfaces based on the two methods and their variants, including the first
      and second cumulant expansion of the exponentially weighted work and the Gaussian
      position approximation for the delta function in Hummer and Szabo's expression.
      We find that with large harmonic force constants, the second cumulant expansion
      performs well in conjunction with either the stiff spring approximation or the
      Hummer-Szabo method. When interpreting dynamic force spectroscopy (pullings at
      different speeds), the second cumulant expansion of the stiff spring
      approximation performs the best when pulling velocities are similar, but variants
      of the Hummer-Szabo perform the best when they are spread over a large spectrum.
      While these conclusion are not definitive for all systems, the insights should
      prove useful for scientists interpreting nonequilibrium pulling experiments.

PMID- 18088109
TI  - A pseudopotential for improving the packing of ellipsoidal protein structures
      determined from NMR data.
AB  - A pseudopotential has been introduced into NMR protein structure determination
      that effectively restrains molecular volume based on the observation that rigid,
      well-packed protein structures are approximately ellipsoidal. Allowing an
      ellipsoidal shape is more general than the single approximately spherical shape
      imposed by the radius of gyration pseudopotential introduced previously. We
      demonstrate that this new gyration volume term improves structures both during
      the calculation of an initial unknown fold and during final refinement.

PMID- 18088110
TI  - Phase diagram for assembly of biologically-active peptide amphiphiles.
AB  - We construct a phase diagram for self-assembling biologically active peptide
      amphiphiles. The structure and stability of the assemblies are studied as a
      function of pH and salinity of the solution. The general features of the phase
      diagram are predicted based on theoretical modeling of the self-assembly process,
      as well as experimental data, and further experiments are performed to verify and
      ascertain the boundary locations of the diagram. Depending on solution
      conditions, the amphiphiles can form cylindrical or spherical micelles,
      intermediate structures between these, or may not assemble at all. We also
      demonstrate that changing conditions may result in phase transitions among these
      structures. This type of phase diagram could be useful in the design of certain
      supramolecular nanostructures by providing information on the necessary
      conditions to form them.

PMID- 18088111
TI  - Stability and reversibility of LiBH4.
AB  - LiBH4 is a complex hydride and exhibits a high gravimetric hydrogen density of
      18.5 wt %. Therefore it is a promising hydrogen storage material for mobile
      applications. The stability of LiBH4 was investigated by pcT (pressure,
      concentration, and temperature) measurements under constant hydrogen flows and
      extrapolated to equilibrium. According to the van 't Hoff equation the following
      thermodynamic parameters are determined for the desorption: enthalpy of reaction
      DeltarH = 74 kJ mol-1 H2 and entropy of reaction DeltarS = 115 J K-1 mol-1 H2.
      LiBH4 decomposes to LiH + B + 3/2H2 and can theoretically release 13.9 wt %
      hydrogen for this reaction. It is shown that the reaction can be reversed at a
      temperature of 600 degrees C and at a pressure of 155 bar. The formation of LiBH4
      was confirmed by XRD (X-ray diffraction). In the rehydrided material 8.3 wt %
      hydrogen was desorbed in a TPD (temperature-programmed desorption) measurement
      compared to 10.9 wt % desorbed in the first dehydrogenation.

PMID- 18088112
TI  - Oxidation of organic films by beams of hydroxyl radicals.
AB  - We have studied the oxidation of self-assembled monolayers (SAMs) of alkanes and
      alkenes with a thermal beam of OH radicals. The target films were produced by
      bonding alkane thiols and alkene thiols to a gold surface and the SAMs are
      mounted in a vacuum chamber at a base pressure of 10-9 Torr. Hydroxyl radicals
      were produced by a corona discharge in an Ar/H2O2/water mixture. The resultant
      molecular beam was scanned by an electrostatic hexapole and the OH radicals [4
      (+/- 1) x 1011 OH radicals cm-2 sec-1] were focused onto the target SAM. All of
      the hydroxyl radicals impinging on the SAM surface are rotationally (J' ' </=
      5/2) cold. The vibrational temperature of the radicals is estimated to be 1700
      3400 K which implies that between 5% and 22% of the hydroxyl radical beam is
      OHv=1 and the remainder (95% to 78%) is OHv=1. The collision energy of the beam
      with the SAM is 333 cm-1 corresponding to a 485 K thermal beam. We employed
      reflection/absorption infrared spectroscopy (RAIRS) to monitor the reactivity of
      OH with an alkane and an alkene SAM. RAIRS demonstrated that a 10 min dose of OH
      radicals largely destroys the CH3- groups at the interface. This corresponds to a
      deposition of 2.4 x 1014 OH cm-2 or about 60% of the SAM monolayer. Oxidation of
      an undec-10-ene-1-thiol (HS(CH2)9HC=CH2) SAM with OH radicals proceeded more
      quickly with all the terminal alkenes, -CH=CH2, eliminated within 5 min following
      deposition of 1.2 x 1014 radicals. We believe that the OH radicals initiate a
      radical-induced polymerization of the alkene film.

PMID- 18088114
TI  - Structural phase stability studies on MBeH3 (M = Li, Na, K, Rb, Cs) from density
      functional calculations.
AB  - Density functional theory calculations within the generalized-gradient
      approximation are used to establish the ground-state structure, equilibrium
      structural parameters, and electronic structure for MBeH(3) phases. From the 24
      structural arrangements used as inputs for structural optimization calculations,
      the ground-state crystal structures of MBeH(3) phases have been predicted. At
      ambient conditions, LiBeH(3) and NaBeH(3) crystallize with perovskite-related
      orthorhombic and cubic structures, respectively. The remaining phases KBeH(3),
      RbBeH(3), and CsBeH(3) crystalize in a monoclinic structure. In the predicted
      phases one can store up to 15.93 wt % of hydrogen. The formation energy for the
      MBeH(3) phases have been investigated along different reaction pathways. The
      electronic structures reveal that all these phases are insulators with estimated
      band gaps varying between 1.79 and 3.44 eV.

PMID- 18088113
TI  - Routes to new hafnium(IV) tetraaryl porphyrins and crystal structures of unusual
      phosphate-, sulfate-, and peroxide-bridged dimers.
AB  - New routes for the synthesis of mono tetraaryl porphyrinato hafnium(IV)
      complexes, Hf(IV)Por(L)(2), are reported, where the secondary ligands, L, are
      determined by the method of purification. These synthetic routes cater to the
      solubility of the macrocycles and provide access to Hf(IV) complexes of meso
      tetraaryl porphyrins bearing diverse functional groups such as phenyl, tolyl,
      pyridyl, pentafluorophenyl, and carboxyphenyl. The latter three derivatives
      significantly expand the repertoire of hafnium porphyrinates. One route refluxes
      the porphyrin with HfCl(4) in 1-chloronaphthalene or in a mixed solvent of 1
      chloronaphthalene and o-cresol. A second, solventless method is also reported
      wherein the porphyrin is mixed with Hf(cp)(2)Cl(2) and heated to give the
      metalated porphyrin in good yields. Simultaneous purification and formation of
      stable porphyrinato hafnium(IV) diacetate complexes, Hf(Por)OAc(2), is
      accomplished by elution over silica gel using 3-5% acetic acid in the eluent.
      Exchange of the acetate ligands for other oxo-bearing ligands can be nearly
      quantitative, such as p-aminobenzoate (PABA), pentanoate (pent), or octanoate
      (oct). Notably, we find that two to three of a variety of small multitopic
      dianions such as peroxo (O(2)(-2)), SO(4)(-2), and HPO(4)(-2) serve to bridge
      between two Hf(Por) moieties to form stable dimers. The crystal structures of
      this library of Hf(Por) complexes are reported, and we note that careful analysis
      of crystallography data reveals (Por)Hf(micro-eta(2)-O(2))(2)Hf(Por) rather than
      four bridging oxo or hydroxy ions.

PMID- 18088115
TI  - Rhenium(I) polypyridine biotin isothiocyanate complexes as the first luminescent
      biotinylation reagents: synthesis, photophysical properties, biological labeling,
      cytotoxicity, and imaging studies.
AB  - We report here the design of the first class of luminescent biotinylation
      reagents derived from rhenium(I) polypyridine complexes. These complexes [Re(N
      N)(CO)(3)(py-biotin-NCS)](PF(6)) (py-biotin-NCS = 3-isothiocyanato-5-(N-((2
      biotinamido)ethyl)aminocarbonyl)pyridine; N-N = 1,10-phenanthroline (phen) (1a),
      3,4,7,8-tetramethyl-1,10-phenanthroline (Me(4)-phen) (2a), 4,7-diphenyl-1,10
      phenanthroline (Ph(2)-phen) (3a)), containing a biotin unit and an isothiocyanate
      moiety, have been synthesized from the precursor amine complexes [Re(N
      N)(CO)(3)(py-biotin-NH(2))](PF(6)) (py-biotin-NH(2) = 3-amino-5-(N-((2
      biotinamido)ethyl)aminocarbonyl)pyridine; N-N = phen (1c), Me(4)-phen (2c), Ph(2)
      phen (3c)). To investigate the amine-specific reactivity of the isothiocyanate
      complexes 1a-3a, they have been reacted with a model substrate ethylamine,
      resulting in the formation of the thiourea complexes [Re(N-N)(CO)(3)(py-biotin-TU
      Et)](PF(6)) (py-biotin-TU-Et = 3-ethylthioureidyl-5-(N-((2
      biotinamido)ethyl)aminocarbonyl)pyridine; N-N = phen (1b), Me(4)-phen (2b), Ph(2)
      phen (3b)). All the rhenium(I) complexes have been characterized, and their
      photophysical properties have been studied. The avidin-binding properties of the
      thiourea complexes 1b-3b have been examined by the 4'-hydroxyazobenzene-2
      carboxylic acid (HABA) assay. Titration results indicated that the complexes
      exhibited emission enhancement by ca. 1.4-1.5-fold upon binding to avidin, and
      the lifetimes were elongated to ca. 0.8-2.0 micros. Additionally, we have
      biotinylated bovine serum albumin (BSA) with the isothiocyanate complexes. All
      the resultant rhenium-BSA bioconjugates displayed intense and long-lived orange
      yellow to greenish-yellow emission upon irradiation in aqueous buffer under
      ambient conditions. The avidin-binding properties of the bioconjugates have been
      investigated using the HABA assay. Furthermore, the cytotoxicity of the thiourea
      complexes 1b-3b toward the HeLa cells has been examined by the 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC50 values were
      determined to be ca. 17.5-28.5 microM, which are comparable to that of cisplatin
      (26.7 microM) under the same conditions. The cellular uptake of complex 3b has
      been investigated by fluorescence microscopy, and the results showed that the
      complex was localized in the perinuclear region after interiorization.

PMID- 18088116
TI  - Three new organically templated 1D, 2D, and 3D vanadates: synthesis, crystal
      structures, and characterizations.
AB  - Three new vanadate compounds of the formulas (C(2)N(2)H(10))VO(OH)(4) (I),
      (NH(4))(3)(C(3)N(2)H(5))V(4)O(10) (II), and V(OH)(3).0.97H(2)O (III) have been
      synthesized by a solvothermal method and characterized by IR spectroscopy,
      elemental analysis, and thermogravimetric analysis. The crystal structures of the
      above three vanadates have been established by single-crystal X-ray diffraction.
      Compound I crystallizes as tetragonal, space group P4/mmm, with a = 9.0465(11) A,
      c = 3.9897(10) A, V = 326.51(10) A(3), and Z = 2. Compound II crystallizes as
      orthorhombic, space group Immm, with a = 3.6012(10) A, b = 11.312(4) A, c =
      15.050(4) A, V = 613.1(3) A3, and Z = 2. Compound III crystallizes as cubic,
      space group Fd3m, with a = 10.4252(17) A, V = 1133.1(3) A(3), and Z = 16.
      Structural analyses reveal a one-dimensional beeline-chained structure, which
      consists of VO(6) octahedra in I. Compound II possesses a two-dimensional V-O
      layered structure formed by VO(5) square pyramids; protonated imidazole and
      remaining NH(4+) cations are inserted between the layers. The three-dimensional
      open framework of III with the pyrochlore type consists of V(12) and V(4)
      secondary building units by using VO(6) octahedra as building units.

PMID- 18088117
TI  - Covalent-like interactions between artificial atoms inside silver supercrystals.
AB  - In this paper, a description of the process by which two kinds of surfactants
      with relative long or short alkyl chains are introduced onto the surface of Ag
      nanocrystals, which contribute to the formation of tunable and anisotropic
      "covalent bonds" between two Ag nanocrystals, is given. By altering the lengths
      of the short alkyl chains, the sizes and structures of the as-obtained
      supercrystals as well as the exposed crystal planes of the interior nanocrystals
      can be tuned. This strategy may further enrich the "chemical bond" categories of
      artificial atoms and serve as the base for the discovery of more functional
      superstructures.

PMID- 18088118
TI  - Rapid protein-ligand costructures using chemical shift perturbations.
AB  - Structure-based drug discovery requires the iterative determination of protein
      ligand costructures in order to improve the binding affinity and selectivity of
      potential drug candidates. In general, X-ray and NMR structure determination
      methods are time consuming and are typically the limiting factor in the drug
      discovery process. The application of molecular docking simulations to filter and
      evaluate drug candidates has become a common method to improve the throughput and
      efficiency of structure-based drug design. Unfortunately, molecular docking
      methods suffer from common problems that include ambiguous ligand conformers or
      failure to predict the correct docked structure. A rapid approach to determine
      accurate protein-ligand costructures is described based on NMR chemical shift
      perturbation (CSP) data routinely obtained using 2D 1H-15N HSQC spectra in high
      throughput ligand affinity screens. The CSP data is used to both guide and filter
      AutoDock calculations using our AutoDockFilter program. This method is
      demonstrated for 19 distinct protein-ligand complexes where the docked conformers
      exhibited an average rmsd of 1.17 +/- 0.74 A relative to the original X-ray
      structures for the protein-ligand complexes.

PMID- 18088120
TI  - Cation-cation pi-pi stacking in small ionic clusters of 1,2,4-triazolium.

PMID- 18088121
TI  - High gas storage capacities for ionic liquids through chemical complexation.

PMID- 18088119
TI  - A combinatorial method for solution-phase synthesis of labeled bivalent beta-turn
      mimics.
AB  - Piperidine-functionalized, 1,4-disubstituted-1,2,3-triazoles of generic structure
      1 were conceived as "minimalist" mimics of peptidic beta-turn structures. Key
      features of these molecules include (i) the possibility of incorporating amino
      acid side chains corresponding to many of the protein amino acids; (ii) a close
      correspondence of separations of these side chains to i + 1 to i + 2 residues in
      turns; (iii) facile adjustment of the side-chain vectors on docking while only
      influencing two critical degrees of freedom; and (iv) some electrostatic
      polarity. Fifteen monomers of this type were made via copper-mediated
      cycloaddition reactions. Solution-phase methodologies were devised to assemble
      these monomers into bivalent compounds in high purity states (typically >85%) so
      that they could be used in first-pass biological assays without further
      purification. The skeleton for forming these bivalent compounds is triazine
      based. There is a third site which allowed for introduction of a fluorescent
      label (library of compounds 2) or an alkyne-functionalized triethylene glycol
      chain (library of compounds 3) included to promote water-solubility and to allow
      incorporation of probes via copper-mediated cycloaddition reactions. In the
      event, two 135-membered libraries were prepared, one consisting of compounds 2
      and the other of 3. No protecting groups or coupling agents were required; these
      attributes of the method were important to allow most of the products to be
      obtained in over 85% purities. The fluorescein-tagged library of compounds 2 was
      screened in a fluorescence-activated cell sorting (FACS) assay using cells
      transfected to overexpress one of the following neurotrophin receptors: TrkA,
      TrkC, and p75. Preliminary findings indicate four compounds 2gm, 2gn, 2gi, and
      2gj bound the TrkA receptor selectively; all of these contain a threonine-lysine
      turn mimic. Thus, a pharmacological probe for the TrkA receptor has been
      developed.

PMID- 18088122
TI  - Synthesis and conformational studies of gamma-aminoxy peptides.
AB  - We have synthesized a series of gamma-aminoxy acids, including unsubstituted and
      gamma4-Ph-, gamma4-alkyl-, and gamma(3,4)-cyclohexyl-substituted systems.
      Coupling of these monomers to oligomers can be realized using EDCI/HOBt (or HOAt)
      as the coupling agent. gamma-Aminoxy peptides can form 10-membered-ring
      intramolecular hydrogen bonds-so-called "gamma N-O turns"-between adjacent
      residues, the extent of which is controlled by the nature of the side chain of
      each gamma-aminoxy acid residue, increasing from the unsubstituted gamma-aminoxy
      peptide to the gamma4-alkyl aminoxy peptides to the gamma4-phenyl- and gamma(3,4)
      cyclohexyl-substituted aminoxy peptides. The presence of two consecutive
      homochiral 10-membered-ring intramolecular hydrogen bonds leads to the formation
      of a novel helical structure. Theoretical studies on a series of model peptides
      rationalize very well the experimentally observed conformational features of
      these gamma-aminoxy peptides.

PMID- 18088123
TI  - A single-molecule assay to directly identify solvent-accessible disulfide bonds
      and probe their effect on protein folding.

PMID- 18088124
TI  - Evaluation of the functional role of the heme-6-propionate side chain in
      cytochrome P450cam.

PMID- 18088126
TI  - Iron(II)-templated synthesis of [3]rotaxanes by passing two threads through the
      same ring.

PMID- 18088125
TI  - Biodegradable pH-sensing dendritic nanoprobes for near-infrared fluorescence
      lifetime and intensity imaging.

PMID- 18088127
TI  - Highly site- and enantioselective Cu-catalyzed allylic alkylation reactions with
      easily accessible vinylaluminum reagents.

PMID- 18088128
TI  - Enzymatic oxidation of H2 in atmospheric O2: the electrochemistry of energy
      generation from trace H2 by aerobic microorganisms.

PMID- 18088129
TI  - Transition-metal-free synthesis of poly(phenylene ethynylene)s with alternating
      aryl-perfluoroaryl units.

PMID- 18088131
TI  - Synthesis of water-soluble dendrimers based on melamine bearing 16 paclitaxel
      groups.
AB  - The design, synthesis, and characterization of triazine dendrimers derivatized
      with the anticancer agent paclitaxel are described. The precursor generation two
      dendrimer 1 is prepared in six linear steps in 64% overall yield and presents 16
      amines and two groups for radioiodination. This macromolecule is subsequently
      derivatized with a paclitaxel conjugate to yield a generation three dendrimer, 2,
      which is then pegylated in two steps. The pegylated final products, 4a and 4b,
      with molecular weights of 46 and 77 kDa, respectively, solubilize paclitaxel in
      water. Pegylated dendrimer 4a is 30 wt % paclitaxel, 52 wt % PEG, and 18 wt %
      dendrimer. Target 4b is 18 wt % paclitaxel, 71 wt % PEG, and 11 wt % dendrimer.

PMID- 18088132
TI  - Design and synthesis of cyclic RGD pentapeptoids by consecutive Ugi reactions.
AB  - A new strategy for the synthesis of cyclic peptoids was developed. The approach
      is based on the use of consecutive Ugi reactions for the assembly of the acyclic
      peptoid and for the ring closure. Cyclopentapeptoid analogues of the RGD peptides
      were designed and synthesized using this methodology. The results confirm the
      versatility and efficiency of the method for the preparation of cyclic
      oligopeptoids.

PMID- 18088133
TI  - Electrophilic C12 building blocks for alkaloids: formal total synthesis of (+/-)
      maritidine.
AB  - Silyl-protected benzyl alcohol derivatives and the salt 1 are used to form ortho
      substituted C12 electrophilic organoiron building blocks which are converted into
      a spirocyclic cyclohexenone to complete a formal total synthesis of (+/-)
      maritidine (5). The choice of TBDPS protection was shown to be better than TIPS
      and compatible with ipso nucleophile addition to form a quaternary center. The
      reaction sequence is the first example of a successful application in the
      synthesis of an arylcyclohexadienyliron complex with an ortho-carbon substituent
      in the position required for Amaryllidaceae alkaloids of this type.

PMID- 18088134
TI  - First synthesis of 4'-selenonucleosides showing unusual Southern conformation.
AB  - The first synthesis of 4'-selenonucleosides was achieved using a Pummerer-type
      condensation as a key step. All stereoelectronic effects shown in 4'
      oxonucleosides were overwhelmed by the size of selenium and steric interactions,
      driving the conformation to the C2'-endo/ C3'-exo twist (Southern) conformation.

PMID- 18088135
TI  - Nonplanar aromatic compounds. 9. Synthesis, structure, and aromaticity of
      1:2,13:14-dibenzo[2]paracyclo[2](2,7)- pyrenophane-1,13-diene.
AB  - Pyrenophane (6) and an octaphenyl derivative (16) were synthesized using two
      different routes. Both cyclophanes contain a severely bent pyrene unit (6: theta
      = 93.6 degrees and 16: theta = 95.8 degrees , according to DFT-calculations
      (B3LYP/6-311G**)), which was generated at room temperature by a valence
      isomerization/dehydrogenation (VID) reaction. HOMA and NICS indicate 92-98%
      retention of aromaticity of the highly distorted pyrene systems compared to
      planar pyrene.

PMID- 18088136
TI  - Stereospecific and stereoselective alkyl and silylcyclopropanation of alpha,beta
      unsaturated amides.
AB  - A novel chromium-promoted alkyl- and silyl cyclopropanation of (E)- or (Z)
      alpha,beta-unsaturated amides in which the C-C double bond is di-, or
      trisubstituted is described. This process takes place with total
      stereospecificity, and the new stereogenic center is generated with high or total
      stereoselectivity. A mechanism is proposed to explain the cyclopropanation
      reaction.

PMID- 18088137
TI  - Studies toward the enantioselective syntheses of oxylipins: total synthesis and
      structure revision of solandelactone E.
AB  - An efficient and general entry to unsaturated cyclopropane- and lactone
      containing oxylipins of marine origin has been designed and applied to the first
      enantioselective total synthesis of solandelactone E. The synthesis, which
      proceeds in a total of 23 steps from commercially available materials, features a
      diastereoselective acetal-directed cyclopropanation of an electron-deficient
      diene, a regioselective Sharpless enantioselective dihydroxylation, and a
      stereoselective [2,3]-sigmatropic rearrangement of a selenoxide to effect a 1,3
      transposition of an allylic alcohol. Comparison of spectral data for the
      synthetic solandelactone, thus prepared, with data in the literature led to a
      revision of the original structural assignments of the C(11)-epimeric
      solandelactones.

PMID- 18088138
TI  - Atropisomerism in the 2-arylimino-N-(2-hydroxyphenyl)thiazoline series: influence
      of hydrogen bonding on the racemization process.
AB  - A series of original atropisomeric iminothiazolines 1 in which X = OH or (and) Y
      = OH were prepared from the corresponding methoxy precursors. The resolution of
      the atropisomeric enantiomers on chiral support is reported, and the barriers to
      enantiomerization are given. These barriers were determined either by off-line
      racemization studies or by treatment of the plateau-shape chromatogram during
      chromatography on chiral support. When X = OH, the barriers are quite low due to
      the development of a hydrogen bond between the proton of the OH group and the
      nitrogen of the imino group. For these compounds, plateau shape chromatograms
      were obtained during HPLC on chiral support. DFT calculations confirmed the
      occurrence of hydrogen bonding all along the rotation process and produced
      calculated barriers in close agreement with the experimental data. Compound 1i
      (OH, OH) in which both X and Y are hydroxy groups was particularly easy to
      prepare by demethylation with BBr3 of the dimethoxy precursor. Since the above
      mentioned precursor is readily available from N,N'-bis(2-methoxyphenyl)thiourea
      and 1-chloropropan-2-one, 1i (OH, OH) is a good candidate for further
      functionalization. Atropisomerism in a 12-membered bridged bisether prepared from
      1i (OH, OH) is reported as an illustrating example.

PMID- 18088139
TI  - Multiorbital interactions during Acyl radical addition reactions involving imines
      and electron-rich olefins.
AB  - Ab initio and DFT calculations reveal that acyl radicals add to imines and
      electron-rich olefins through simultaneous SOMO --> pi*, pi --> SOMO, and HOMO -
      > pi*C=O interactions between the radical and the radicalophile. At the
      CCSD(T)/aug-cc-pVDZ//QCISD/cc-pVDZ level, energy barriers of 15.6 and 17.9 kJ
      mol(-1) are calculated for the attack of the acetyl radical at the carbon and
      nitrogen ends of methanimine, respectively. These barriers are 17.1 and 20.4 kJ
      mol(-1) at BHandHLYP/cc-pVDZ. In comparison, barriers of 34.0 and 23.4 kJ mol(-1)
      are calculated at BHandHLYP/cc-pVDZ for reaction of the acetyl radical at the 1-
      and 2-positions in aminoethylene, repectively. Natural bond orbital (NBO)
      analysis at the BHandHLYP/6-311G** level of theory reveals that SOMO -->
      pi*imine, pi imine--> SOMO, and LPN --> pi*C=O interactions are worth 90, 278,
      and 138 kJ mol-1, respectively, in the transition state (2) for reaction of
      acetyl radical at the nitrogen end of methanimine; similar interactions are
      observed for the chemistry involving aminoethylene. These multiorbital
      interactions are responsible for the unusual motion vectors associated with the
      transition states involved in these reactions. NBO analyses for the remaining
      systems in this study support the hypothesis that the acetyl radical is
      ambiphilic in nature.

PMID- 18088140
TI  - Convenient one-pot synthesis of 2,2-bis-(4-hydroxyphenyl)-cyclopentanone.
AB  - 2,2-Bis-(4-hydroxyphenyl)-cyclopentanone (3a) was unexpectedly obtained in 76%
      yield from a reductive coupling reaction of 4,4'-dihydroxybenzophenone (1a) and
      cyclobutanone with TiCl4 and Zn. Further optimization showed that catechol as an
      external ligand and a hydroxy group on benzophenone facilitated the generation of
      a quinonemethide (intermediate II) that is involved in the pinacol-type
      rearrangement of intermediate I to give the rearranged product.

PMID- 18088141
TI  - Regioselective syntheses of beta-N-linked glycoaminoacids and glycopeptides.
AB  - Acylation of tetra-O-pivaloyl-beta-D-galactopyranosylamine 2 by readily available
      N- (Cbz or Fmoc-alpha-aminoacyl) benzotriazoles under microwave irradiation
      proceeded diastereoselectively to give beta-N-glycoaminoacids 3a-d, (3c+3c')
      (compound numbers written within brackets represent a racemate or a
      diastereomeric mixture; compound numbers without brackets represent a single
      enantiomer) (83-92%), and glycosylated asparagine building block 9 (65%). N-Cbz
      Protected peptidoylbenzotriazoles 4a-c similarly afforded beta-N-glycodipeptides
      5a-c (76-81%). Regiospecific beta-N-linkage formation was established by 1D and
      2D NMR techniques for 3b.

PMID- 18088142
TI  - Face-selective Diels-Alder reactions between unsymmetrical cyclohexadienes and
      symmetric trans-dienophile: an experimental and computational investigation.
AB  - A combined experimental and theoretical study of the Diels-Alder reactions
      between 2-trimethylsiloxy-1,3-cyclohexadienes (2-11) and (E)-1,4-diphenylbut-2
      ene-1,4-dione (1) is reported. Two diastereomeric products, 5-endo-6-exo- (nx)
      and 5-exo-6-endo- (xn) dibenzoyl derivatives, are possible with symmetric trans
      dienophile (1). While in many cases 5-endo-6-exo product is preferred over the
      corresponding 5-exo-6-endo product, the product ratio nx:xn is found to vary with
      the position of substituents on the diene. The density functional theory studies
      with the mPW1PW91/6-31G* as well as the B3LYP/6-31G* levels reveal that the
      electrostatic repulsion between the oxygen lone pairs on the diene and the
      dienophile is critical to the observed product selectivities. The optimized
      transition state geometries though appeared to involve secondary orbital
      interactions, careful examination of the frontier Kohn-Sham orbitals as well as
      calculations with the natural bond orbital (NBO) analyses confirm the absence of
      SOI in these transition states. In the case of methyl-substituted dienes, a
      cumulative effect of steric and electrostatic interactions between the diene and
      the dienophile is found to be the controlling element toward the observed
      selectivity.

PMID- 18088143
TI  - Synthesis and evaluation of substrate analogues as mechanism-based inhibitors of
      type II isopentenyl diphosphate isomerase.
AB  - Type 2 isopentenyl diphosphate isomerase (IDI-2), which catalyzes the
      interconversion of isopentenyl diphosphate and dimethylallyl diphosphate,
      contains a tightly bound molecule of FMN. To probe the mechanism of the reaction,
      cyclopropyl and epoxy substrate analogues, designed to be mechanism-based
      irreversible inhibitors, were synthesized and evaluated with IDI-2 from Thermus
      thermophilus. The cyclopropyl analogues were alternative substrates. The epoxy
      analogue was an irreversible inhibitor, with kI = 0.37 +/- 0.07 min(-1) and KI =
      1.4 +/- 0.3 microM. LC-MS studies revealed formation of an epoxide-FMN adduct.

PMID- 18088144
TI  - A diastereoselective ring contraction of 1,3-dioxepins to 2,3,4-trisubstituted
      and tetrasubstituted tetrahydrofurans.
AB  - A modular and diastereoselective approach to 2,3,4-trisubstituted and
      tetrasubstituted tetrahydrofurans is reported. The use of dioxepins containing an
      embedded vinyl acetal functionality leads to a Lewis acid-mediated [1,3] ring
      contraction to afford tetrahydrofurans in good yield and excellent
      diastereoselectivity. The use of TMSOTf in MeCN leads to the 2,3-cis/3,4-trans
      diastereomer while SnCl4 in CH2Cl2 provides the 2,3-trans/3,4-cis diastereomer. A
      variety of substituents are tolerated at each position. The presence of Lewis
      basic functionality under the SnCl4 conditions alters the reaction favoring the
      diastereomer formed under the TMSOTf conditions. We present conclusive evidence
      that the products of each of these reactions are formed under kinetic control. We
      further provide stereochemical models consistent with each of these rearrangement
      reactions that account for the formation of the major diastereomer in each case.

PMID- 18088145
TI  - Enantioselective aza-Diels-Alder reaction of aldimines with "Danishefsky-type
      diene" catalyzed by chiral scandium(III)-N,N'-dioxide complexes.
AB  - A new kind of complex prepared from scandium(III) triflate and l-proline-derived
      N,N'-dioxides has been developed to catalyze the enantioselective aza-Diels-Alder
      reaction between 1,3-butadiene (diene 1) and aldimines 2, affording the
      corresponding 2,5-disubstituted dihydropyridinones in moderate to high yields (up
      to 92%) with good enantioselectivities (up to 90% ee) at room temperature. A
      variety of aldimines including aromatic, heteroaromatic, conjugated, and
      aliphatic imines were found to be suitable substrates. Enantiopure samples (up to
      99% ee) were obtained for some products by a single recrystallization. The
      absolute configuration of the products was determined by X-ray diffraction and CD
      analysis. On the basis of the investigation of 1H NMR spectra and the positive
      nonlinear effect, the catalyst structure was carefully discussed.

PMID- 18088146
TI  - PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols: an
      efficient synthesis of 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives.
AB  - A PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols
      was observed to provide an efficient route to 4-(1',3'-dien-2'-yl)-2,5
      dihydrofuran derivatives. By using the easily available optically active starting
      materials, 2,5-dihydrofurans with high enantiopurity may be prepared. A Pd(II)
      catalyzed mechanism was also discussed.

PMID- 18088147
TI  - Preparation, photocatalytic activities, and dye-sensitized solar-cell performance
      of submicron-scale TiO2 hollow spheres.
AB  - We prepared submicron-scale spherical hollow particles of anatase TiO2 by using a
      polystyrene-bead template. The obtained particles were very uniform in size, with
      a diameter of 490 nm and a shell thickness of 30 nm. The Brunauer-Emmett-Teller
      surface area measurements revealed a large value of 70 m2/g. The photocatalytic
      property was investigated by the complete decomposition of gaseous isopropyl
      alcohol under UV irradiation. It was indicated that the activity of the hollow
      spheres was 1.8 times higher than that of the conventional P25 TiO2 nanoparticles
      with a diameter of 30 nm. Furthermore, we fabricated a dye-sensitized solar cell
      (DSC) using an electrode of the TiO2 hollow spheres, and examined the
      photovoltaic performance under simulated sunlight. Although the per-area
      efficiency was rather low (1.26%) because of a low area density of TiO2 on the
      electrode, the per-weight efficiency was 2.5 times higher than those of the
      conventional DSCs of TiO2.

PMID- 18088148
TI  - (CH3)3SiCl/SiCl4 azeotrope grows superhydrophobic nanofilaments.
AB  - We describe the vapor-phase reaction (at room temperature and 40-45% relative
      humidity) of silicon wafers with the azeotropic mixture of trimethylchlorosilane
      and tetrachlorosilane. Water contact angle analysis indicates that surfaces
      become nearly perfectly hydrophobic (thetaA/thetaR > or =176 degrees/> or =176
      degrees) after 2 min of reaction. SEM analysis at various reaction times shows
      the growth of nanofilaments with diameters of approximately 30 nm. X-ray
      photoelectron spectroscopy of oxidized titanium surfaces that were exposed to the
      azeotrope vapor indicates that the product is derived from a approximately 10:1
      ratio of SiCl4 and (CH3)3SiCl. A mechanism for filament growth is proposed.

PMID- 18088149
TI  - Using collagen fiber as a template to synthesize hierarchical mesoporous alumina
      fiber.
AB  - Hierarchical mesoporous alumina fiber was synthesized by using collagen fiber as
      the template, and characterized by means of scanning electron microscopy,
      transmission electron microscopy, N2 adsorption techniques, X-ray photoelectron
      spectroscopy, and X-ray diffraction. The alumina fiber obtained is approximately
      1-4 microm in outer diameter and 0.5-1 mm in length. The pore size distribution
      of the alumina fiber is narrow (2-20 nm), and its pore size is controllable by
      varying preparation methods. This study indicates that collagen fiber, which has
      hierarchical supermolecular structure, could be used as an ideal template to
      prepare well-defined porous metal oxide fibers.

PMID- 18088150
TI  - Hydrogen storage in carbon nanotubes through the formation of stable C-H bonds.
AB  - To determine if carbon-based materials can be used for hydrogen storage, we have
      studied hydrogen chemisorption in single-walled carbon nanotubes. Using atomic
      hydrogen as the hydrogenation agent, we demonstrated that maximal degree of
      nanotube hydrogenation depends on the nanotube diameter, and for the diameter
      values around 2.0 nm nanotube-hydrogen complexes with close to 100% hydrogenation
      exist and are stable at room temperature. This means that specific carbon
      nanotubes can have a hydrogen storage capacity of more than 7 wt % through the
      formation of reversible C-H bonds.

PMID- 18088151
TI  - Single-molecule detection and mismatch discrimination of unlabeled DNA targets.
AB  - We report on a single-molecule readout scheme on total internal reflection
      fluorescence microscopy (TIRFM) demonstrating a detection limit in the low fM
      regime for short (30-mer) unlabeled DNA strands. Detection of unlabeled DNA
      targets is accomplished by letting them mediate the binding of suspended
      fluorescently labeled DNA-modified small unilamellar vesicles (O approximately
      100 nm) to a DNA-modified substrate. On top of rapid and sensitive detection, the
      technique is also shown capable of extracting kinetics data from statistics of
      the residence time of the binding reaction in equilibrium, that is, without
      following neither the rate of binding upon injection nor release upon rinsing.
      The potential of this feature is demonstrated by discriminating a single mismatch
      from a fully complementary sequence. The success of the method is critically
      dependent on a surface modification that provides sufficiently low background.
      This was achieved through self-assembly of a biotinylated copolymer, Poly(L
      lysine)-g-poly(ethylene glycol) (PLL-g-PEG) on a silicon dioxide surface,
      followed by subsequent addition of streptavidin and biotinylated DNA. The
      proposed detection scheme is particularly appealing due to the simplicity of the
      sensor, which relies on self-assembly principles and conventional TIRFM.
      Therefore, we foresee a great potential of the concept to serve as an important
      component in future multiplexed sensing schemes. This holds in particular true in
      cases when information about binding kinetics is valuable, such as in single
      nucleotide polymorphism diagnostics.

PMID- 18088152
TI  - Monitoring single-molecule reactivity on a carbon nanotube.
AB  - Using point-functionalized carbon nanotube devices, we demonstrate continuous,
      multihour monitoring of a single carboxylate group interacting with its immediate
      environment. The conductance of the nanotube device directly transduces single
      molecule attachments and detachments in the presence of the carboxylate-selective
      reagent 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC).
      Because only one carboxylate is present in the device, it can be studied through
      hundreds of reactions, providing the statistical accuracy to directly determine a
      12 s lifetime of the carboxy-EDC complex. An additional instability of the
      complex is transduced in real time and observed to have a median lifetime of 2
      ms. By determining a turnover time in good agreement with bulk measurements and
      simultaneously illuminating additional dynamics, these results demonstrate this
      platform's potential for complementing optical methods in single-molecule
      research.

PMID- 18088153
TI  - Noncovalent functionalization of carbon nanotubes with amphiphilic gd3+ chelates:
      toward powerful t1 and t2 MRI contrast agents.
AB  - An amphiphilic gadolinium (III) chelate (GdL) was synthesized from commercially
      available stearic acid. Aqueous solutions of the complex at different
      concentrations (from 1 mM to 1 microM) were prepared and adsorbed on multiwalled
      carbon nanotubes. The resulting suspensions were stable for several days and have
      been characterized with regard to magnetic resonance imaging (MRI) contrast agent
      applications. Longitudinal water proton relaxivities, r1, have been measured at
      20, 300, and 500 MHz. The r1 values show a strong dependence on the GdL
      concentration, particularly at low field. The relaxivities decrease with
      increasing field as it is predicted by the Solomon-Bloembergen-Morgan theory.
      Transverse water proton relaxation times, T2, have also been measured and are
      practically independent of both the frequency and the GdL concentration. An in
      vivo feasibility MRI study has been performed at 300 MHz in mice. A negative
      contrast could be well observed after injection of a suspension of functionalized
      nanotubes into the muscle of the leg of the mouse.

PMID- 18088154
TI  - The new myth: the social value of the QALY.

PMID- 18088155
TI  - The last decade of Italian pharmaceutical policy: instability or consolidation?
AB  - Pharmaceutical policy in Italy has been reshaped as a result of the 1993-4 crisis
      in which it was revealed that pharmaceutical companies, policy makers and top
      Department of Health officers had constructed an illegal system to set prices.
      Following this crisis, the rise of technical competency and leadership in the
      Italian Department of Health and, since 2000, in the Drug Regulatory Agency
      (Agenzia Italiana del Farmaco; AIFA) has achieved major improvements in many
      aspects of Italian pharmaceutical policy. These improvements have included
      increased transparency of decision making, the use of evidence-based medicine
      principles for reimbursement and pricing, and the use of generic drugs to lower
      prices.As a result of these changes, pharmaceutical expenditure has been
      controlled and equity has improved, mainly because co-payments have been reduced,
      thus reducing private expenditure on reimbursable drugs. However, a short-term
      approach to cost containment has prevailed, and Italian pharmaceutical policy has
      neglected industrial parameters. Hence, the trend in pharmaceutical expenditure
      has been erratic, and Italy has not favoured localization of research and
      development and production in its territory. The dominant issue of Italian health
      policy in recent years has been devolution of powers to regions, the intermediate
      tier of the Italian State. Overall, devolution has increased regional
      accountability on healthcare spending. However, regions react to enhanced freedom
      in different ways, reflecting their institutional capacity and competencies. This
      process has also affected pharmaceutical policy, more than in other decentralized
      healthcare systems (such as Germany and Spain). Such a situation is causing
      increasing regional variations and geographical equity concerns. In addition, the
      regional level appears rather inadequate to promote an industrial perspective
      unless it is supported by national initiatives.

PMID- 18088156
TI  - Cost-effectiveness analyses of hepatitis A vaccine: a systematic review to
      explore the effect of methodological quality on the economic attractiveness of
      vaccination strategies.
AB  - Hepatitis A vaccines have been available for more than a decade. Because the
      burden of hepatitis A virus has fallen in developed countries, the appropriate
      role of vaccination programmes, especially universal vaccination strategies,
      remains unclear. Cost-effectiveness analysis is a useful method of relating the
      costs of vaccination to its benefits, and may inform policy. This article
      systematically reviews the evidence on the cost effectiveness of hepatitis A
      vaccination in varying populations, and explores the effects of methodological
      quality and key modelling issues on the cost-effectiveness ratios.Cost
      effectiveness/cost-utility studies of hepatitis A vaccine were identified via a
      series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI). Citations and
      full-text articles were reviewed independently by two reviewers. Reference
      searching, author searches and expert consultation ensured literature saturation.
      Incremental cost-effectiveness ratios (ICERs) were abstracted for base-case
      analyses, converted to $US, year 2005 values, and categorised to reflect various
      levels of cost effectiveness. Quality of reporting, methodological issues and key
      modelling issues were assessed using frameworks published in the
      literature.Thirty-one cost-effectiveness studies (including 12 cost-utility
      analyses) were included from full-text article review (n = 58) and citation
      screening (n = 570). These studies evaluated universal mass vaccination (n = 14),
      targeted vaccination (n = 17) and vaccination of susceptibles (i.e. individuals
      initially screened for antibody and, if susceptible, vaccinated) [n = 13]. For
      universal vaccination, 50% of the ICERs were <$US20 000 per QALY or life-year
      gained. Analyses evaluating vaccination in children, particularly in high
      incidence areas, produced the most attractive ICERs. For targeted vaccination,
      cost effectiveness was highly dependent on the risk of infection.Incidence,
      vaccine cost and discount rate were the most influential parameters in
      sensitivity analyses. Overall, analyses that evaluated the combined hepatitis
      A/hepatitis B vaccine, adjusted incidence for under-reporting, included societal
      costs and that came from studies of higher methodological quality tended to have
      more attractive cost-effectiveness ratios. Methodological quality varied across
      studies. Major methodological flaws included inappropriate model type,
      comparator, incidence estimate and inclusion/exclusion of costs.

PMID- 18088157
TI  - Carmustine implants for the treatment of newly diagnosed high-grade gliomas: a
      cost-utility analysis.
AB  - BACKGROUND: High-grade gliomas are aggressive brain tumours that are extremely
      challenging to treat effectively. The intracranial implantation of carmustine
      wafers (BCNU-W), which delivers chemotherapy directly to the affected area, may
      prolong survival in this population. However, no attention has yet been paid to
      the economic implications of BCNU-W in this setting. OBJECTIVE: To investigate
      the cost effectiveness of BCNU-W as an adjunct to surgery followed by
      radiotherapy, compared with surgery plus radiotherapy alone. Newly diagnosed,
      operable grade III and IV gliomas in a population with a mean age of 55 years
      were considered. METHODS: A Markov cost-utility model was developed in Microsoft
      Excel, adopting a UK NHS perspective. Transition probabilities and cost data
      (year 2004 values) were obtained from published literature or expert opinion. The
      model incorporated utility values, obtained from members of the public,
      reflecting the quality of life associated with high-grade glioma. The effects of
      uncertainty were explored through extensive one-way and probabilistic sensitivity
      analysis. RESULTS: Surgery with the implantation of BCNU-W followed by
      radiotherapy costs pound sterling 54 500 per additional QALY gained when compared
      with surgery plus radiotherapy alone. Probabilistic sensitivity analysis shows a
      <10% probability that BCNU-W would be considered cost effective at a willingness
      to-pay threshold of pound sterling 30 000 per QALY. Although model outputs were
      sensitive to alterations in several key parameters, the incremental cost
      effectiveness of the intervention remained above pound sterling 30 000 per QALY
      in all analyses. CONCLUSION: Compared with usual care for the treatment of newly
      diagnosed high-grade gliomas, BCNU-W is unlikely to be considered a cost
      effective use of healthcare resources when judged by the standards commonly
      adopted in England and Wales. However, the dreadful prognosis of the condition
      and the paucity of alternative therapies are additional issues that healthcare
      commissioners may choose to take into account when considering an adoption
      decision.

PMID- 18088158
TI  - Dynamic modelling of infectious diseases: an application to the economic
      evaluation of influenza vaccination.
AB  - OBJECTIVE: To evaluate the economic efficiency of influenza vaccination using
      both dynamic and static modelling approaches. SETTING: The Spanish National
      Health System. DESIGN AND METHODS: We modelled the progress of an influenza
      epidemic in Spain according to the epidemiological pattern of susceptible-
      >infective-->resistant, employing a non-linear system of ordinary differential
      equations that enables the measurement of epidemiological effects of an anti
      influenza vaccination. We used a decision tree to represent the repercussion on
      healthcare resources use and on financial resources. The same analyses were
      conducted using a static approach, and the results were compared. Healthcare
      costs were valued in euro, year 2005 values. RESULTS: For the base case, the
      impact of the healthcare intervention (vaccination) was not efficient from the
      perspective of the healthcare payer when using a static approach (return rate
      0.28 per euro invested in vaccination). Nevertheless, it was efficient when
      employing a dynamic approach (return rate 1.22 per euro). Furthermore, a
      considerable freeing of healthcare resources would have been produced over the
      entire influenza season. CONCLUSIONS: The indirect effect of vaccination on the
      non-vaccinated individuals (the 'herd immunity effect') can be greater than the
      direct effect on individuals vaccinated. This implies that the herd immunity
      effect needs to be taken into consideration in the economic evaluations of
      prophylactic measures employed against infectious diseases.

PMID- 18088159
TI  - Economic burden of bilateral neovascular age-related macular degeneration: multi
      country observational study.
AB  - BACKGROUND: There is limited previous research examining the healthcare costs of
      neovascular age-related macular degeneration (NV-AMD), which constrains our
      understanding of the economic impact of this condition. With aging populations,
      this leading cause of rapid vision loss in Western countries is expected to
      become a pressing health predicament, requiring decision makers to evaluate
      alternative treatment strategies for AMD. OBJECTIVE: To document the economic
      burden of bilateral NV-AMD, the late stage of AMD, in elderly patients, from a
      societal perspective. STUDY DESIGN, SETTING AND PARTICIPANTS: A cross-sectional,
      observational study surveyed 401 patients with bilateral NV-AMD and 471 non-AMD
      subjects in Canada, France, Germany, Spain and the UK. Physicians' records and
      subjects' standardized telephone interviews were used to record medical resource
      utilization, assistance with daily living and social benefits. Annual bilateral
      NV-AMD-related socioeconomic costs were calculated in euro, year 2005 values.
      MAIN OUTCOME MEASURES: Societal costs including direct vision-related medical
      costs (e.g. treatment of AMD and vision-related equipment), direct non-vision
      related medical costs (e.g. medications) and direct non-medical-related costs
      (e.g. home healthcare and social services) were the main outcome measures.
      RESULTS: The demographic profile of NV-AMD patients was similar across countries;
      however, co-morbid condition profiles varied. NV-AMD patients reported
      substantial health-related problems and associated health resource utilization
      (HRU). In the previous 12 months, 12-22% of patients fell, and half of these
      patients required medical treatments. More than 20% (range 21-59%) of patients
      were prescribed vision-enhancing equipment. More than half of the patients (54
      81%) were living with a spouse or family member and 19-41% reported receiving
      assistance for activities of daily living. The average annual societal cost per
      bilateral NV-AMD patient treated was estimated to be euro 7879 in Canada, euro
      7349 in France, euro 12 445 in Germany, euro 5732 in Spain and euro 5300 in the
      UK, and direct vision-related medical costs accounted for 23-63% of the total
      cost. Half of the patients were diagnosed with bilateral NV-AMD for <1 year, with
      an average length of 5 months; there were no statistically significant
      differences in total annual costs per patient between these patients and those
      who were diagnosed with bilateral disease for > or =1 year. Estimated annual
      societal costs of bilateral NV-AMD patients in these countries ranged from euro
      268 to euro 1311 million. Estimated annual societal costs of all NV-AMD patients
      in these countries ranged from euro 671 to euro 3278 million. CONCLUSIONS:
      Bilateral NV-AMD imposes significant functional impairment on patients, leading
      to increased HRU and a high societal cost burden. Differences in national
      healthcare systems and NV-AMD treatment patterns were reflected in the wide
      variation of NV-AMD costs across the five surveyed countries. Even though the
      prevalence rates and per-patient costs varied by country, the societal costs of
      NV-AMD patients were substantial in each country. Earlier intervention with
      effective therapies is expected to reduce disease burden and disability
      associated with NV-AMD and, thus, decrease the overall societal cost.

PMID- 18088160
TI  - Cost effectiveness of itraconazole in the prophylaxis of invasive fungal
      infections.
AB  - BACKGROUND: Invasive fungal infections in neutropenic patients treated for
      haematological malignancies are associated with a high mortality rate and,
      therefore, require early treatment. As the diagnosis of invasive fungal
      infections is difficult, effective antifungal prophylaxis is desirable. So far,
      fluconazole has been the most commonly used. OBJECTIVE: To assess the cost
      effectiveness of itraconazole compared with both fluconazole and no prophylaxis
      for the prevention of invasive fungal infections in haematological patients, mean
      age 51 years, in Germany and The Netherlands. STUDY DESIGN: We designed a
      probabilistic decision model to fully incorporate the uncertainty associated with
      the risk estimates of acquiring an invasive fungal infection. These risk
      estimates were extracted from two meta-analyses, evaluating the effectiveness of
      fluconazole and itraconazole and no prophylaxis. The perspective of the analysis
      was that of the healthcare sector; only medical costs were taken into account.
      All costs were reported in euro, year 2004 values.Cost effectiveness was
      expressed as net costs per invasive fungal infection averted. No discounting was
      performed, as the model followed patients during their neutropenic period, which
      was assumed to be less than 1 year. RESULTS: According to our probabilistic
      decision model, the monetary benefits of averted healthcare exceed the costs of
      itraconazole prophylaxis under baseline assumptions (95% CI: from cost-saving to
      euro 5000 per invasive fungal infection averted). Compared with fluconazole,
      itraconazole is estimated to be both more effective and more economically
      favourable, with a probability of almost 98%. CONCLUSIONS: In specific groups of
      neutropenic patients treated for haematological malignancies, itraconazole
      prophylaxis could potentially reduce overall healthcare expenditure, without
      harming effectiveness, in settings where fluconazole is common practice in the
      prophylaxis of invasive fungal infections.

PMID- 18088161
TI  - Effectiveness and safety of vitamin D in relation to bone health.
AB  - OBJECTIVES: To review and synthesize the literature in the following areas: the
      association of specific circulating 25(OH)D concentrations with bone health
      outcomes in children, women of reproductive age, postmenopausal women and elderly
      men; the effect of dietary intakes (foods fortified with vitamin D and/or vitamin
      D supplementation) and sun exposure on serum 25(OH)D; the effect of vitamin D on
      bone mineral density (BMD) and fracture or fall risk; and the identification of
      potential harms of vitamin D above current reference intakes. DATA SOURCES:
      MEDLINE(R) (1966-June Week 3 2006); Embase (2002-2006 Week 25); CINAHL (1982-June
      Week 4, 2006); AMED (1985 to June 2006); Biological Abstracts (1990-February
      2005); and the Cochrane Central Register of Controlled Trials (2nd Quarter 2006).
      REVIEW METHODS: Two independent reviewers completed a multi-level process of
      screening the literature to identify eligible studies (title and abstract,
      followed by full text review, and categorization of study design per key
      question). To minimize bias, study design was limited to randomized controlled
      trials (RCTs) wherever possible. Study criteria for question one were broadened
      to include observational studies due to a paucity of available RCTs, and question
      four was restricted to systematic reviews to limit scope. Data were abstracted in
      duplicate and study quality assessed. Differences in opinion were resolved
      through consensus or adjudication. If clinically relevant and statistically
      feasible, meta-analyses of RCTs on vitamin D supplementation and bone health
      outcomes were conducted, with exploration of heterogeneity. When meta-analysis
      was not feasible, a qualitative systematic review of eligible studies was
      conducted. RESULTS: 167 studies met our eligibility criteria (112 RCTs, 19
      prospective cohorts, 30 case-controls and six before-after studies). The largest
      body of evidence on vitamin D status and bone health was in older adults with a
      lack of studies in premenopausal women and infants, children and adolescents. The
      quality of RCTs was highest in the vitamin D efficacy trials for prevention of
      falls and/or fractures in older adults. There was fair evidence of an association
      between low circulating 25(OH)D concentrations and established rickets. However,
      the specific 25(OH)D concentrations associated with rickets is uncertain, given
      the lack of studies in populations with dietary calcium intakes similar to North
      American diets and the different methods used to determine 25(OH)D
      concentrations. There was inconsistent evidence of an association of circulating
      25(OH)D with bone mineral content in infants, and fair evidence that serum
      25(OH)D is inversely associated with serum PTH. In adolescents, there was fair
      evidence for an association between 25(OH)D levels and changes in BMD. There were
      very few studies in pregnant and lactating women, and insufficient evidence for
      an association between serum 25(OH)D and changes in BMD during lactation, and
      fair evidence of an inverse correlation with PTH. In older adults, there was fair
      evidence that serum 25(OH)D is inversely associated with falls, fair evidence for
      a positive association with BMD, and inconsistent evidence for an association
      with fractures. The imprecision of 25(OH)D assays may have contributed to the
      variable thresholds of 25(OH)D below which the risk of fractures, falls or bone
      loss was increased. There was good evidence that intakes from vitamin D-fortified
      foods (11 RCTs) consistently increased serum 25(OH)D in both young and older
      adults. Eight randomized trials of ultraviolet (UV)-B radiation (artificial and
      solar exposure) were small and heterogeneous with respect to determination of the
      exact UV-B dose and 25(OH)D assay but there was a positive effect on serum
      25(OH)D concentrations. It was not possible to determine how 25(OH)D levels
      varied by ethnicity, sunscreen use or latitude. Seventy-four trials examined the
      effect of vitamin D(3) or D(2) on 25(OH)D concentrations. Most trials used
      vitamin D(3), and the majority enrolled older adults. In three trials, there was
      a greater response of serum 25(OH)D concentrations to vitamin D(3) compared to
      vitamin D(2), which may have been due to more rapid clearance of vitamin D(2) in
      addition to other mechanisms. Meta-analysis of 16 trials of vitamin D(3) was
      consistent with a dose-response effect on serum 25(OH)D when comparing daily
      doses of <400 IU to doses >/= 400 IU. An exploratory analysis of the
      heterogeneity demonstrated a significant positive association comparable to an
      increase of 1 - 2 nmol/L in serum 25(OH)D for every 100 additional units of
      vitamin D although heterogeneity remained after adjusting for dose. Vitamin D(3)
      in combination with calcium results in small increases in BMD compared to placebo
      in older adults although quantitative synthesis was limited due to variable
      treatment durations and BMD sites. The evidence for fracture reduction with
      vitamin D supplementation was inconsistent across 15 trials. The combined results
      of trials using vitamin D(3) (700 - 800 IU daily) with calcium (500 - 1,200 mg)
      was consistent with a benefit on fractures although in a subgroup analysis by
      setting, benefit was primarily in elderly institutionalized women (fair evidence
      from two trials). There was inconsistent evidence across 14 RCTs of a benefit on
      fall risk. However, a subgroup analysis showed a benefit of vitamin D in
      postmenopausal women, and in trials that used vitamin D(3) plus calcium. In
      addition, there was a reduction in fall risk with vitamin D when six trials that
      adequately ascertained falls were combined. Limitations of the fall and fracture
      trials included poor compliance with vitamin D supplementation, incomplete
      assessment of vitamin D status and large losses to follow-up. We did not find any
      systematic reviews that addressed the question on the level of sunlight exposure
      that is sufficient to maintain serum 25(OH)D concentrations but minimizes risk of
      melanoma and non-melanoma skin cancer. There is little evidence from existing
      trials that vitamin D above current reference intakes is harmful. In most trials,
      reports of hypercalcemia and hypercalciuria were not associated with clinically
      relevant events. The Women's Health Initiative study did report a small increase
      in kidney stones in postmenopausal women aged 50 to 79 years whose daily vitamin
      D(3) intake was 400 IU (the reference intake for 50 to 70 years, and below the
      reference intake for > 70 years) combined with 1000 mg calcium. The increase in
      renal stones corresponded to 5.7 events per 10,000 person-years of exposure. The
      women in this trial had higher calcium intakes than is seen in most post
      menopausal women. CONCLUSIONS: The results highlight the need for additional high
      quality studies in infants, children, premenopausal women, and diverse racial or
      ethnic groups. There was fair evidence from studies of an association between
      circulating 25(OH)D concentrations with some bone health outcomes (established
      rickets, PTH, falls, BMD). However, the evidence for an association was
      inconsistent for other outcomes (e.g., BMC in infants and fractures in adults).
      It was difficult to define specific thresholds of circulating 25(OH)D for optimal
      bone health due to the imprecision of different 25(OH)D assays. Standard
      reference preparations are needed so that serum 25(OH)D can be accurately and
      reliably measured, and validated. In most trials, the effects of vitamin D and
      calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium
      supplementation compared to placebo has a small beneficial effect on BMD, and
      reduces the risk of fractures and falls although benefit may be confined to
      specific subgroups. Vitamin D intake above current dietary reference intakes was
      not reported to be associated with an increased risk of adverse events. However,
      most trials of higher doses of vitamin D were not adequately designed to assess
      long-term harms.

PMID- 18088162
TI  - Treatment of primary and secondary osteoarthritis of the knee.
AB  - OBJECTIVES: Systematic review of outcomes of three treatments for osteoarthritis
      (OA) of the knee: intra-articular viscosupplementation; oral glucosamine,
      chondroitin or the combination; and arthroscopic lavage or debridement. DATA
      SOURCES: We abstracted data from: 42 randomized, controlled trials (RCTs) of
      viscosupplementation, all but one synthesized among six meta-analyses; 21 RCTs of
      glucosamine/chondroitin, 16 synthesized among 6 meta-analyses; and 23 articles on
      arthroscopy. The search included foreign-language studies and relevant conference
      proceedings. REVIEW METHODS: The review methods were defined prospectively in a
      written protocol. We sought systematic reviews, meta-analyses, and RCTs published
      in full or in abstract. Where randomized trials were few, we sought other study
      designs. We independently assessed the quality of all primary studies. RESULTS:
      Viscosupplementation trials generally report positive effects on pain and
      function scores compared to placebo, but the evidence on clinical benefit is
      uncertain, due to variable trial quality, potential publication bias, and unclear
      clinical significance of the changes reported. The Glucosamine/Chondroitin
      Arthritis Intervention Trial (GAIT), a large (n=1,583), high-quality, National
      Institutes of Health-funded, multicenter RCT showed no significant difference
      compared to placebo. Glucosamine sulfate has been reported to be more effective
      than glucosamine hydrochloride, which was used in GAIT, but the evidence is not
      sufficient to draw conclusions. Clinical studies of glucosamine effect on glucose
      metabolism are short term, or if longer (e.g., 3 years), excluded patients with
      metabolic disorders. The best available evidence for arthroscopy, a single sham
      controlled RCT (n=180), showed that arthroscopic lavage with or without
      debridement was equivalent to placebo. The main limitations of this trial are the
      use of a single surgeon and enrollment of patients at a single Veterans Affairs
      Medical Center. No studies reported separately on patients with secondary OA of
      the knee. The only comparative study was an underpowered, poor-quality trial
      comparing viscosupplementation to arthroscopy with debridement. CONCLUSIONS:
      Osteoarthritis of the knee is a common condition. The three interventions
      reviewed in this report are widely used in the treatment of OA of the knee, yet
      the best available evidence does not clearly demonstrate clinical benefit.
      Uncertainty regarding clinical benefit can be resolved only by rigorous,
      multicenter RCTs. In addition, given the public health impact of OA of the knee,
      research on new approaches to prevention and treatment should be given high
      priority.

PMID- 18088163
TI  - Antiretroviral (ARV) drug resistance in the developing world.
AB  - OBJECTIVES: To describe the overall prevalence of ARV resistance in the
      developing world, focusing on: (1) treatment naive populations, (2) the
      resistance consequences of prevention of mother to child transmission (pMTCT)
      drug regimens, and (3) the relationship of medication adherence to resistance.
      DATA SOURCES: We searched PubMed(R), EMBASE, the Cochrane Controlled Clinical
      Trials Register Database, and the Cochrane Database of Reviews of Effectiveness
      (DARE). Additional sources of evidence included the Stanford University HIV Drug
      Resistance Database; reports of WATCH: Worldwide Analysis of Resistance
      Transmission over Time of Chronically and Acute Infected HIV-1 infected persons;
      a recent unpublished pMTCT overview; and various conference proceedings. Studies
      that did not report original research, that reported data already reported in
      another article, and case studies of fewer than 20 individuals were excluded. Of
      1,122 titles identified, 117 journal articles and presentations were included.
      REVIEW METHODS: We abstracted data on geographic region, number of participants,
      subject demographics, HIV viral clade, medications taken (if any), years of data
      collection, how people were selected for resistance testing, and how and when
      resistance was assessed. Because of study heterogeneity, pooling was not
      possible; thus, the data are summarized qualitatively. Differences by region,
      population group, and HIV viral clade are described. RESULTS: The patterns of ARV
      resistance among treatment naive populations worldwide appear to reflect
      geographic trends in use of ARV medications. A worldwide surveillance program
      (WATCH) found the rate of resistance (to any drug) among treatment naive
      individuals was 5.5 percent in Africa, 7.4 percent in East Asia, 5.7 percent in
      Southeast Asia, and 6.4 percent in Latin America, lower than in North America
      (11.4 percent) and Europe (10.6 percent). Resistance data on HIV clades other
      than A, B, C, and D were too scarce to permit reliable conclusions. We also
      identified very few studies designed to assess the effect of health services
      delivery factors or medication adherence on the development of resistance in
      patients in developing countries. Evidence provided by longitudinal analyses
      suggests that, among women taking intrapartum single dose nevirapine (SD-NVP) to
      prevent mother-to-child transmission of HIV, both the overall prevalence of NNRTI
      resistance as well as the frequency of mutant virus in the overall viral
      population decreases with time since SD-NVP prophylaxis was received.
      CONCLUSIONS: In future resistance studies, rare HIV clades should be over-sampled
      in order to provide statistically meaningful data. Resistance surveillance
      programs should be maintained throughout the developing world, and data should be
      reported and analyzed in a consistent and timely manner. Where resources permit,
      studies of adherence in developing regions should conduct resistance testing.

PMID- 18088164
TI  - Three-dimensional CT examination of the mastication system in the giant anteater.
AB  - The gross anatomy of the mastication system of the giant anteater (Myrmecophaga
      tridactyla) was examined by means of three-dimensional image analysis. The
      anteater rotates the mandibles medially and laterally to control its tongue when
      it is elongated and to house it when it is relaxed. Three-dimensional CT image
      analysis demonstrated that the shape and size of the oral cavity changes
      drastically when the mandibles are rotated. The oral cavity expands bilaterally
      when the dorsal part of the mandibles bend medially. Macroscopic observations and
      muscle-weight data supported the observation that the superficial temporal and
      medial pterygoid muscles act as the main medial and lateral rotators of the
      mandible, respectively. The low height of the mandibular ramus and the incomplete
      zygomatic arch in this species represent adaptations for the rotational movement
      of the mandibles, since they both contribute to the medially oriented
      transmission of force from the temporal muscles and to preventing collision
      between the mandibles and the cranium during the rotational movement.

PMID- 18088165
TI  - Osteological morphometrics of Australian chelonioid turtles.
AB  - Extant and fossil Australian chelonioid turtles were examined for 57 osteological
      morphometric variables. Data were analysed using principal components analysis
      and canonical variates analysis, after Burnaby isometric 'size' removal, as well
      as multivariate allometry. Results indicate that Lepidochelys spp. are
      proportionately differentiated from other Cheloniidae. The majority of chelonioid
      osteological variables scale isometrically, with less than a third exhibiting
      positive or negative allometry. Skull length and width, postero-ventral skull,
      mandible length, scapular and pubic variables are found to be useful for
      differentiating between extant and extinct chelonioids. Skull length and width,
      mandible height, jaw symphysis length, premaxilla height, femoral length,
      scapular, pelvic, plastral and rib variables are established as useful
      differentiators of cheloniids. Australian fossil protostegids are
      morphometrically more similar to cheloniids than dermochelyids, and no cranial
      morphometric evidence could be found for the presence of more than one
      protostegid species. Some osteological allometric variables may be valuable for
      use in determining the relationships of chelonioids; however these should be
      examined in conjunction with morphology-based cladistic analyses to test
      established phylogenies.

PMID- 18088166
TI  - Muscarinic excitation in grasshopper song control circuits is limited by
      acetylcholinesterase activity.
AB  - The species- and situation-specific sound production of grasshoppers can be
      stimulated by focal application of both nicotinic and muscarinic receptor
      agonists into the central body complex of the protocerebrum. Pressure injection
      of the intrinsic transmitter acetylcholine only elicits fast and short-lived
      responses related to nicotinic receptor-mediated excitation. Prolonged sound
      production that includes complex song patterns requires muscarinic receptor
      mediated excitation. In addition, basal muscarinic excitation in the central body
      neuropil seems to determine the general motivation of a grasshopper to
      stridulate. To demonstrate that endogenous acetylcholinesterase limits the
      activation of muscarinic receptors by synaptically released acetylcholine in the
      central body of Chorthippus biguttulus, we investigated both its presence in the
      brain and effects on sound production resulting from inhibition of esterase
      activity. Acetylcholinesterase activity was detected in the upper and lower
      division of the central body. Both these neuropils known to be involved in the
      cephalic control of stridulation were also shown to contain muscarinic
      acetylcholine receptors expressed by columnar neurons suggested to serve as
      output neurons of the central complex. Pressure injection of the
      acetylcholinesterase inhibitor eserine into protocerebral control circuits of
      restrained male grasshoppers stimulated long-lasting stridulation that depended
      on scopolamine-sensitive muscarinic receptors. In restrained males, eserine
      released the typical response song by potentiating the stimulatory effect of the
      conspecific female song. Eserine-mediated inhibition of acetylcholinesterase in
      the central body prolongs the presence of synaptically released acetylcholine at
      its postsynaptic receptors and increases its potency to activate muscarinic
      receptor-initiated signaling pathways acting to promote grasshopper sound
      production.

PMID- 18088167
TI  - Spermatogenesis in the testes of diapause and non-diapause pupae of the sweet
      potato hornworm, Agrius convolvuli (L.) (Lepidoptera: Sphingidae).
AB  - Dichotomous spermatogenesis was examined in relation to diapause in the sweet
      potato hornworm, Agrius convolvuli. In non-diapause individuals, eupyrene
      metaphase began during the fifth larval instar and eupyrene spermatids appeared
      in wandering larvae. Bundles of mature sperm were found after pupation. Apyrene
      spermatocytes also appeared during the fifth larval instar, but meiotic divisions
      occurred irregularly and their nuclei were discarded from the cells during
      spermiogenesis. Morphometric analyses of flagellar axonemes showed a variable
      sperm number in apyrene bundles. The variation ranging from 125 to 256 sperm per
      bundle indicated abnormal divisions or the elimination of apyrene spermatocytes.
      In diapause-induced hornworms, spermatogenesis progressed similarly during the
      larval stages. The cessation of spermatogenesis during diapause is characterized
      by 1) secondary spermatocytes and sperm bundles degenerating gradually as the
      diapause period lengthens, and 2) spermatogonia or primary spermatocytes
      appearing throughout diapause. A TUNEL (TdT-mediated dUTP-biotin nick end
      labeling) assay revealed that DNA fragmentation occurred in the nuclei of
      secondary spermatocytes and early spermatids. Aggregates of heterochromatin along
      the nuclear membrane indicated the onset of apoptosis, and condensed chromatin
      was confirmed by electron microscopy to be the apoptotic body. These results show
      that the degenerative changes in spermatogenic cells during pupal diapause were
      controlled by apoptosis.

PMID- 18088168
TI  - A new species of Deiratonotus (Crustacea: Brachyura: Camptandriidae) found in the
      Kumanoe River Estuary, Kyushu, Japan.
AB  - Camptandriid crabs collected in the Kumanoe River Estuary, Kyushu, Japan were
      studied on the basis of morphological characters and molecular analysis. As a
      result, a new species, Deiratonotus kaoriae, was recognized. These crabs were
      found mainly in a creek of the sandy tidal flat within the Kumanoe River Estuary.
      The new species shares a very diagnostic character, the presence of a transverse
      ridge on the carapace, with D. cristatus (de Man, 1895) and differs markedly from
      the other congeners that lack this feature. The new species, however, differs
      from D. cristatus in the absence of harpoon-shaped setae on the subdistal end of
      the first gonopod and the presence of an extremely reduced second abdominal
      segment. According to a molecular analysis based on 12S+16S mitochondrial rRNA
      gene sequences, with Cleistostoma dilatatum (de Haan, 1833) and Camptandrium
      sexdentatum Stimpson, 1858 as outgroups, Deiratonotus kaoriae is more closely
      related to D. cristatus than to D. japonicus (Sakai, 1934).

PMID- 18088169
TI  - Description of a sexually dimorphic oribatid mite (Arachnida: Acari: Oribatida)
      from canopy habitats of the Ryukyu Archipelago, southwestern Japan.
AB  - A new species in the monotypic genus Symbioribates, S. aokii sp. nov., is
      described on the basis of adult material collected from canopy habitats and wind
      traps in the Ryukyu Archipelago, southwestern Japan. Symbioribates aokii sp. nov.
      expresses different dimorphism in the octotaxic system from that of the type
      species, S. papuensis Aoki, 1966. The characteristics of this genus and its
      relationships to others of the superfamily Oripodoidea are discussed and a
      revised diagnosis of the family is given.

PMID- 18088170
TI  - Analysis of behavioral selection after sensory deprivation of legs in the cricket
      Gryllus bimaculatus.
AB  - An air puff stimulus evoked the swimming of an intact cricket, Gryllus
      bimaculatus, placed on a water surface. When only the forelegs were intact,
      swimming was initiated frequently, but flying was never initiated. On the other
      hand, flying was initiated when only the middle legs or hindlegs were intact.
      Therefore, the sensory inputs from the forelegs are important in the initiation
      of swimming and for the inhibition of flying when on the water surface. After
      bilateral ablation of the middle legs and hindlegs, the bilateral segments of the
      remaining forelegs were sequentially ablated from the distal area to the proximal
      area of the legs. After bilateral ablation of all tarsomeres, the relative
      occurrence of swimming decreased and that of flying increased. After the
      following ablation of the bilateral tibiae, most insects responded to an air puff
      stimulus by flying. Experiments performed after coating the leg surface with
      enamel resulted in almost the same behavioral change as that observed in the
      ablation experiments. These results suggest that the sensory receptors
      responsible for the initiation of swimming and the inhibition of flying are
      mainly located on the surface of the tibia and the tarsus of the forelegs. The
      behavioral change between swimming and walking was also studied using
      methylcellulose solutions of various viscosities. On the methylcellulose
      solution, the relative occurrence of walking in the crickets increased with an
      increase in the viscosity of the solution.

PMID- 18088171
TI  - Morphology and electrophysiology of water receptors on legs of the cricket
      Gryllus bimaculatus.
AB  - To identify the sensory organs that are sensitive to water stimuli in the cricket
      Gryllus bimaculatus, cuticular structures on the legs and the number of sensory
      neurons innervating them were studied. Some small hair sensilla on the legs were
      innervated by 2-5 sensory neurons. All such sensilla had a tiny pore at the tip
      of their hairs. The diameter of the pore was approximately 0.2 mum. These
      findings suggest that these are chemosensitive hairs (LCS: leg chemosensillum).
      Of the three pairs of legs, the anterior legs (forelegs) possessed the largest
      number of LCSs. Of the five leg segments (i.e., coxa, trochanter, femur, tibia
      and tarsus), the tarsus possessed the largest number of LCSs on each leg.
      Electrophysiological investigation by tip recording revealed that some of the
      LCSs contained water-receptor cells. Because the basitarsus possessed a larger
      number of LCSs than the other tarsomeres, the distribution of water-receptor
      containing LCSs in the basitarsus of a foreleg was investigated morphologically
      and electrophysiologically. LCSs that contained water-receptor cells were mainly
      distributed on the ventral surface of the basitarsus. There were two types of
      water receptor that showed different response patterns to a stimulus, that is,
      phasic- and tonic-type water receptors. From the distribution of LCSs on the
      legs, the roles of these different types of water receptors in behavioral
      selection, that is, the initiation of swimming and the inhibition of flying, will
      be discussed.

PMID- 18088172
TI  - Interleukin-1alpha stimulates the differentiation of melanocytes but inhibits the
      proliferation of melanoblasts from neonatal mouse epidermis.
AB  - Interleukin (IL)-1alpha is one of the important cytokines involved in regulating
      immunological reactions in the mouse skin. However, it is not known whether IL
      1alpha regulates the proliferation and differentiation of mouse epidermal
      melanocytes. In this study, to investigate the role of IL-1alpha in the
      regulation of the proliferation and differentiation of mouse epidermal
      melanocytes, IL-1alpha was supplemented to serum-free primary cultures of
      epidermal cell suspensions from the initiation of the primary culture
      (keratinocytes and melanoblasts-melanocytes) as well as to pure cultures of
      melanoblasts-melanocytes (keratinocyte-depleted cultures, after 14 days), and its
      effect was tested. IL-1alpha inhibited the proliferation of undifferentiated
      melanoblasts irrespective of the presence or absence of keratinocytes, whereas
      the cytokine inhibited the proliferation of differentiated melanocytes only in
      the presence of keratinocytes. Moreover, IL-1alpha induced the differentiation of
      melanocytes and, in addition, stimulated tyrosinase activity, melanin synthesis,
      and dendritogenesis of melanocytes irrespective of the presence or absence of
      keratinocytes. These results suggest that IL-1alpha is involved in inhibiting the
      proliferation of neonatal murine epidermal melanoblasts and in stimulating the
      differentiation, melanogenesis, and dendritogenesis of melanocytes. The results
      also suggest that IL-1alpha inhibits the proliferation of differentiated
      melanocytes in cooperation with keratinocyte-derived factors.

PMID- 18088173
TI  - Solubilization of the ecdysone binding protein from anterior silk gland cell
      membranes of the silkworm, Bombyx mori.
AB  - We previously provided preliminary evidence for the presence of a putative
      membrane ecdysone receptor (mEcR) anchored in the plasma membranes of anterior
      silk glands (ASGs) in Bombyx mori. This receptor may act in concert with the
      conventional EcR in 20E-dependent programmed cell death of these glands. We
      report here, for the first time, the solubilization of mEcR from ASG membranes
      using the zwitterionic detergent CHAPS in the presence of NaCl. Our results show
      by ligand binding assay that mEcR solubilized this way is functionally active and
      retains 75% of its native binding activity. We also defined experimental
      conditions that yielded protein/detergent complexes with partial binding
      activity, which makes it possible to purify the membrane-bound ecdysone binding
      protein.

PMID- 18088174
TI  - Use of multiple den sites by Eurasian badgers, Meles meles, in a Mediterranean
      habitat.
AB  - Den sites are a conspicuous feature of Eurasian badgers, Meles meles, and in many
      environments include large communal burrows used by several group members. In
      Serra de Grandola, southwest Portugal, nine badgers from three social groups were
      captured and radio collared from 2000 to 2004. A total of 1,787 locations of
      badgers in their resting sites were registered along with a brief description of
      the type of site and weather conditions. Resting sites were grouped according to
      structure (burrows, shrubs, rocks, hollow trees and man-made structures) and
      function (main, secondary and occasional). Although main setts were the most
      frequently used shelter (62.25%), an average of 14 (SD 7.55) resting sites were
      used in each territory. The pattern of use varied seasonally, showing differences
      according to sex and social group. Overall, females used more than twice as many
      occasional resting sites as did males. Generally burrows, predominantly main
      setts, were most frequently used during winter and autumn, whilst non-burrow
      shelters were preferred during spring and summer, when the weather was hot, dry
      and not windy. Proximity to food patches had no apparent influence on the
      location of resting sites. Our results offered no support for the foraging
      related hypotheses that multiple resting sites are a means of conserving energy
      or of maintaining proximity to rich food patches. We suggest that other factors
      such as thermoregulation needs, disturbance, and reproductive status, could be
      influencing the observed pattern of resting-site use by badgers in Serra de
      Grandola.

PMID- 18088175
TI  - Molecular cloning of two estrogen receptors expressed in the testis of the
      Japanese common goby, Acanthogobius flavimanus.
AB  - We isolated cDNA clones of two estrogen receptors (ER1 and ER2) from testis of
      the Japanese common goby (Acanthogobius flavimanus). The cDNAs of ER1 contained
      3,796 nucleotides, including an open reading frame encoding 564 amino acids (Mr:
      61.9 kDa); the cDNA for ER2 was 3,274 nucleotides long, with an open reading
      frame of 567 amino acids (Mr: 63.5 kDa). The deduced aminoacid sequences of ER1
      and ER2 each had a characteristic ER structure consisting of five domains (A/B,
      DNA-binding, D, ligand-binding, and F) and were homologous to ERalpha and ERbeta
      of other vertebrates. We therefore named ER1 and ER2 as goby ERalpha (gERalpha)
      and goby ERbeta (gERbeta), respectively. The DNA- and ligand-binding domains in
      each gER showed high similarity to the corresponding domains of other
      vertebrates. Analysis of the distribution of gERalpha and gERbeta mRNAs in tissue
      by reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed
      that gERalpha was expressed at high levels in brain and testis, and gERbeta was
      expressed most strongly in testis. In situ hybridization showed that the mRNA of
      each gER was expressed mainly in the Sertoli cells of goby testis.

PMID- 18088176
TI  - Globin gene enhancer activity of a DNase-I hypersensitive site-40 homolog in
      medaka, Oryzias latipes.
AB  - In medaka, we found a C16orf35-like gene in the region within 1 Kbp 3' downstream
      of the psibeta end of the 36-Kbp embryonic globin gene cluster ((5')alpha0(3')
      (3')beta1(5')-(5')alpha1(3')-(5')beta2(3')-(5')alpha2(3')-(3')alpha3(5')
      (5')beta3(3')-(3')beta4(5')-(5')alpha4(3')-(3')psialpha(5')-(5')psibeta(3')).
      Intron 5 of the gene contained a region having NF-E2 binding sites located
      between GATA boxes. The region was homologous to human HS-40 in terms of the
      existence and structure of characteristic transcription-factor binding sites and
      was named Ol-HS-40. Injection of the fusion gene construct Ol-HS-40-alpha0(up
      2)GFP, consisting of Ol-HS-40, a 5' upstream 200-bp minimum promoter for alpha0,
      and green fluorescent protein (GFP), showed that Ol-HS-40, as in human HS-40, had
      the ability to strongly enhance GFP expression in erythroid cells of embryos.
      Further analysis using transgenic technology revealed that Ol-HS-40 had the
      ability to change the type of the GFP expression from embryo-to-young fish to
      embryo-to-adult. In addition, the results suggest that Ol-HS-40, although its
      natural function remains unclear, has strong enhancer activity for the expression
      of not only the alpha-globin gene but also the beta-globin gene.

PMID- 18088177
TI  - Gene expression profiles in human lymphocytes irradiated in vitro with low doses
      of gamma rays.
AB  - The molecular mechanisms underlying responses to low radiation doses are still
      unknown, especially in normal lymphocytes, despite the evidence suggesting
      specific changes that may characterize cellular responses. Our purpose was to
      analyze gene expression profiles by DNA microarrays in human lymphocytes after in
      vitro irradiation (10, 25 and 50 cGy) with gamma rays. A cytogenetic analysis was
      also carried out for different radiation doses. G 0 lymphocytes were irradiated
      and induced to proliferate for 48 h; then RNA samples were collected for gene
      expression analysis. ANOVA was applied to data obtained in four experiments with
      four healthy donors, followed by SAM analysis and hierarchical clustering. For
      10, 25 and 50 cGy, the numbers of significantly (FDR <or= 0.05) modulated genes
      were 86, 130 and 142, respectively, and 25, 35 and 33 genes were exclusively
      modulated for each dose, respectively. We found CYP4X1, MAPK10 and ATF6 (10 cGy),
      DUSP16 and RAD51L1 (25 cGy), and RAD50, REV3L and DCLRE1A (50 cGy). A set of 34
      significant genes was common for all doses; while SERPINB2 and C14orf104 were up
      regulated, CREB3L2, DDX49, STK25 and XAB2 were down-regulated. Chromosome damage
      was significantly induced for doses >or=10 cGy (total aberrations) and >or=50 cGy
      (dicentrics/ rings). Therefore, low to moderate radiation doses induced
      qualitative and/or quantitative differences and similarities in transcript
      profiles, reflecting the type and extent of DNA lesions. The main biological
      processes associated with modulated genes were metabolism, stress response/DNA
      repair, cell growth/differentiation, and transcription regulation. The results
      indicate a potential risk to humans regarding the development of genetic
      instability and acquired diseases.

PMID- 18088178
TI  - A Monte Carlo maximum likelihood method for estimating uncertainty arising from
      shared errors in exposures in epidemiological studies of nuclear workers.
AB  - Errors in the estimation of exposures or doses are a major source of uncertainty
      in epidemiological studies of cancer among nuclear workers. This paper presents a
      Monte Carlo maximum likelihood method that can be used for estimating a
      confidence interval that reflects both statistical sampling error and uncertainty
      in the measurement of exposures. The method is illustrated by application to an
      analysis of all cancer (excluding leukemia) mortality in a study of nuclear
      workers at the Oak Ridge National Laboratory (ORNL). Monte Carlo methods were
      used to generate 10,000 data sets with a simulated corrected dose estimate for
      each member of the cohort based on the estimated distribution of errors in doses.
      A Cox proportional hazards model was applied to each of these simulated data
      sets. A partial likelihood, averaged over all of the simulations, was generated;
      the central risk estimate and confidence interval were estimated from this
      partial likelihood. The conventional unsimulated analysis of the ORNL study
      yielded an excess relative risk (ERR) of 5.38 per Sv (90% confidence interval
      0.54-12.58). The Monte Carlo maximum likelihood method yielded a slightly lower
      ERR (4.82 per Sv) and wider confidence interval (0.41-13.31).

PMID- 18088179
TI  - Promoting action of radiation in the atomic bomb survivor carcinogenesis data?
AB  - The age-time patterns of risk in the atomic bomb survivor data on incidence of
      solid cancers suggest an action of low-LET radiation not only on the initiating
      event but also on promotion in a biologically motivated model that allows for
      both actions. The favored model indicates a decrease of radiation risks with age
      at exposure due to the initiating effect and with time since exposure due to the
      promoting effect. These result in a relative risk that depends mostly on attained
      age for ages at exposure above 20 years. According to the model, a dose of 100
      mGy is inducing about the same number of initiating events that occur
      spontaneously in 1 year. Assuming that several mutations are needed to obtain
      intermediate cells with growth advantage does not improve the quality of fit. The
      estimated promoting effect could be explained if the number of intermediate cells
      increases by 80% at 1 Gy, e.g. due to stimulated cell repopulation.

PMID- 18088180
TI  - Relative biological effectiveness of high-energy iron ions for micronucleus
      formation at low doses.
AB  - Dose-response curves for micronucleus (MN) formation were measured in Chinese
      hamster V79 and xrs6 (Ku80(-)) cells and in human mammary epithelial MCF10A cells
      in the dose range of 0.05-1 Gy. The Chinese hamster cells were exposed to 1
      GeV/nucleon iron ions, 600 MeV/nucleon iron ions, and 300 MeV/nucleon iron ions
      (LETs of 151, 176 and 235 keV/microm, respectively) as well as with 320 kVp X
      rays as reference. Second-order polynomials were fitted to the induction curves,
      and the initial slopes (the alpha values) were used to calculate RBE. For the
      repair-proficient V79 cells, the RBE at these low doses increased with LET. The
      values obtained were 3.1 +/- 0.8 (LET = 151 keV/microm), 4.3 +/- 0.5 (LET = 176
      keV/microm), and 5.7 +/- 0.6 (LET = 235 keV/microm), while the RBE was close to 1
      for the repair-deficient xrs6 cells regardless of LET. For the MCF10A cells, the
      RBE was determined for 1 GeV/nucleon iron ions and was found to be 5.5 +/- 0.9,
      slightly higher than for V79 cells. To test the effect of shielding, the 1
      GeV/nucleon iron-ion beam was intercepted by various thicknesses of high-density
      polyethylene plastic absorbers, which resulted in energy loss and fragmentation.
      It was found that the MN yield for V79 cells placed behind the absorbers
      decreased in proportion to the decrease in dose both before and after the iron
      ion Bragg peak, indicating that RBE did not change significantly due to shielding
      except in the Bragg peak region. At the Bragg peak itself with an entrance dose
      of 0.5 Gy, where the LET is very high from stopping low-energy iron ions, the
      effectiveness for MN formation per unit dose was decreased compared to non-Bragg
      peak areas.

PMID- 18088181
TI  - A radiation-induced gene signature distinguishes post-Chernobyl from sporadic
      papillary thyroid cancers.
AB  - We investigated selected gene targets to differentiate radiation-induced
      papillary thyroid cancers (PTCs) from other etiologies. Total RNA was isolated
      from 11 post-Chernobyl PTCs and 41 sporadic PTCs characterized by a more
      aggressive tumor type and lacking a radiation exposure history. RNA from 10 tumor
      samples from both groups was pooled and hybridized separately on a whole genome
      microarray for screening. Then 92 selected gene targets were examined
      quantitatively on each tumor sample using an RTQ-PCR-based low-density array
      (LDA). Screening for more than fivefold differences in gene expression between
      the groups by microarray detected 646 up-regulated and 677 down-regulated genes.
      Categorization of these genes revealed a significant (P < 0.0006) over
      representation of the number of up-regulated genes coding for oxidoreductases, G
      proteins and growth factors, while the number of genes coding for immunoglobulin
      appeared to be significantly down-regulated. With the LDA, seven genes (SFRP1,
      MMP1, ESM1, KRTAP2-1, COL13A1, BAALC and PAGE1) made a complete differentiation
      between the groups possible. Gene expression patterns known to be associated with
      a more aggressive tumor type in older patients appeared to be more pronounced in
      post-Chernobyl PTC, thus underlining the known aggressiveness of radiation
      induced PTC. Seven genes were found that completely distinguished post-Chernobyl
      (PTC) from sporadic PTC.

PMID- 18088182
TI  - The characterization and transmissibility of chromosome aberrations induced in
      peripheral blood lymphocytes by in vitro alpha-particle radiation.
AB  - Peripheral blood lymphocytes were irradiated in vitro with (213)Bi alpha
      particles at doses of 0, 10, 20, 50, 100, 200 and 500 mGy. Chromosome analysis
      was performed on 47-h cultures using single-color fluorescence in situ
      hybridization (FISH) to paint chromosomes 1, 3 and 5. The whole genome was
      analyzed for unstable aberrations to derive aberration frequencies and determine
      cell stability. The dose response for dicentrics was 33.60 +/- 0.47 x 10(-2) per
      Gy. A more detailed analysis revealed that the majority of aberrations scored as
      dicentrics were part of complex/multiple aberrations, with the proportion of
      cells containing complexes increasing with dose. Cells containing aberrations
      involving painted chromosomes (FISH aberrations) were further classified
      according to cell stability and complexity. The majority of cells with FISH
      aberrations were unstable. The proportion of aberrant FISH cells with
      complex/multiple aberrations ranged from 56% at 10 mGy to 89% at 500 mGy. A
      linear dose response for genomic frequencies of translocations in stable cells
      fitted the data from 0 to 200 mGy with a dose response of 7.90 +/- 0.98 x 10(-2)
      per Gy, thus indicating that they are likely to be observed in peripheral blood
      lymphocytes from individuals with past or chronic exposure to high-LET radiation.
      Comparisons with the dose response for low-LET radiation suggest an RBE of 13.6
      for dicentrics in all cells and 3.2 for translocations in stable cells. Since
      stochastic effects of radiation are attributable to genetic changes in viable
      cells, translocations in stable cells may be a better measure when considering
      the comparative risks of different qualities of radiation.

PMID- 18088183
TI  - UVB-radiation-induced apoptosis in Jurkat cells: a coordinated fourier transform
      infrared spectroscopy-flow cytometry study.
AB  - We studied the induction of apoptosis in Jurkat cells by UVB radiation
      (wavelength 290-320 nm) at a dose of 310 mJ/ cm2. We combined Fourier transform
      infrared (FTIR) spectroscopy with flow cytometry to determine whether the
      combination of both techniques could provide new and improved information about
      cell modifications. To do this, we looked for correspondences and correlations
      between spectroscopy and flow cytometry data and found three highly probable
      spectroscopic markers of apoptosis. The behavior of the wave number shift of both
      the Amide I beta-sheet component and the area of the 1083 cm(-1) band reproduced,
      with a high correlation, the behavior of the early apoptotic cell population,
      while the behavior of the Amide I area showed a high correlation with the early
      plus late apoptotic cell population.

PMID- 18088184
TI  - Effect of continuous irradiation with a very low dose of gamma rays on life span
      and the immune system in SJL mice prone to B-cell lymphoma.
AB  - Ionizing radiation has been shown to have dose- and dose-rate-dependent
      carcinogenic effects on the hematopoietic and lymphoreticular systems. We report
      here that continuous exposure to a low dose of gamma rays influences the course
      of spontaneous B-cell lymphoma in SJL mice. We studied the biological effects of
      10 cGy year(-1) gamma rays on the life span of 560 4-week-old SJL/J female mice
      and on various parameters of the cell-mediated immune response. Life span was
      slightly prolonged. The mean survival was 397 days for controls and 417 days for
      irradiated mice that died with lymphoma (P = 0.34). In lymph nodes and spleen,
      lower percentages of CD4+ and CD8+ T cells were observed in irradiated mice
      before 32 weeks. Interestingly, the percentages of CD49+ NK cells were increased
      in the spleens of irradiated mice at 28 weeks (0.61 +/- 0.08% compared to 0.43 +/
      0.12% in controls, P = 0.01) and at 32 weeks (0.62 +/- 0.24% compared to 0.33 +/
      0.09%, P = 0.02), while NK cell activity remained unchanged in exposed mice.
      These results provide further support for the absence of harmful effects of a
      continuous very low dose of radiation on life span and incidence of lymphoma in
      SJL mice.

PMID- 18088185
TI  - Ionizing radiation sensitivity of DNA polymerase lambda-deficient cells.
AB  - Ionizing radiation induces a diverse spectrum of DNA lesions, including strand
      breaks and oxidized bases. In mammalian cells, ionizing radiation-induced lesions
      are targets of non-homologous end joining, homologous recombination, and base
      excision repair. In vitro assays show a potential involvement of DNA polymerase
      lambda in non-homologous end joining and base excision repair. In this study, we
      investigated whether DNA polymerase lambda played a significant role in
      determining ionizing radiation sensitivity. Despite increased sensitivity to
      hydrogen peroxide, lambda-deficient mouse embryonic fibroblasts displayed equal
      survival after exposure to ionizing radiation compared to their wild-type
      counterparts. In addition, we found increased sensitivity to the topoisomerase
      inhibitors camptothecin and etoposide in the absence of polymerase lambda. These
      results do not reveal a major role for DNA polymerase lambda in determining
      radiosensitivity in vivo.

PMID- 18088186
TI  - Effects of exposure of newborn patched1 heterozygous mice to GSM, 900 MHz.
AB  - Patched1 heterozygous knockout mice (Ptc1+/-), an animal model of multiorgan
      tumorigenesis in which ionizing radiation dramatically accelerates tumor
      development, were used to study the potential tumorigenic effects of
      electromagnetic fields (EMFs) on neonatal mice. Two hundred Ptc1+/- mice and
      their wild-type siblings were enrolled in this study. Newborn mice were exposed
      to 900 MHz radiofrequency radiation (average SAR: 0.4 W/kg for 5 days, 0.5 h
      twice a day) or were sham exposed. We found that RF EMFs simulating the Global
      System for Mobile Communications (GSM) did not affect the survival of the mice,
      because no statistically significant differences in survival were found between
      exposed and sham-exposed animals. Also, no effects attributable to radiofrequency
      radiation were observed on the incidence and histology of Ptc1-associated
      cerebellar tumors. Moreover, the skin phenotype was analyzed to look for
      proliferative effects of RF EMFs on the epidermal basal layer and for
      acceleration of preneoplastic lesions typical of the basal cell carcinoma
      phenotype of this model. We found no evidence of proliferative or promotional
      effects in the skin from neonatal exposure to radiofrequency radiation.
      Furthermore, no difference in Ptc1-associated rhabdomyosarcomas was detected
      between sham-exposed and exposed mice. Thus, under the experimental conditions
      tested, there was no evidence of life shortening or tumorigenic effects of
      neonatal exposure to GSM RF radiation in a highly tumor-susceptible mouse model.

PMID- 18088187
TI  - p53-dependent Chk1 phosphorylation is required for maintenance of prolonged G2
      Arrest.
AB  - Targeting checkpoint kinases has been shown to have a potential chemosensitizing
      effect in cancer treatment. However, inhibitors of such kinases preferentially
      abrogate the DNA damage-induced G2 checkpoint in p53-/- as opposed to p53+/+
      cells. The mechanisms by which p53 (TP53) can prevent abrogation of the G2
      checkpoint are unclear. Using normal human diploid p53+/+ and p53-/- fibroblasts
      as model systems, we have compared the effects of three checkpoint inhibitors,
      caffeine, staurosporine and UCN-01, on gamma-radiation-induced G2 arrest. The G2
      arrest in p53+/+ cells was abrogated by caffeine, but not by staurosporine and
      UCN-01, whereas the G2 arrest in p53-/- cells was sensitive to all three
      inhibitors. Chk2 (CHEK1) phosphorylation was maintained in the presence of all
      three inhibitors in both p53+/+ and p53-/- cells. Chk1 phosphorylation was
      maintained only in the presence of staurosporine and UCN-01 in p53+/+ cells. In
      the presence of caffeine Chk1 phosphorylation was inhibited regardless of p53
      status. The pathway of Chk1 phosphorylation --> Cdc25A degradation --> inhibition
      of cyclin B1/Cdk1 activity --> G2 arrest is accordingly resistant to
      staurosporine and UCN-01 in p53+/+ cells. Moreover, sustained phosphorylation of
      Chk1 in the presence of staurosporine and UCN-01 is strongly related to
      phosphorylation of p53. The present study suggests the unique role of Chk1 in
      preventing abrogation of the G2 checkpoint in p53+/+ cells.

PMID- 18088188
TI  - Biophysical models of radiation bystander effects: 1. Spatial effects in three
      dimensional tissues.
AB  - Non-targeted (bystander) effects of ionizing radiation are caused by
      intercellular signaling; they include production of DNA damage and alterations in
      cell fate (i.e. apoptosis, differentiation, senescence or proliferation).
      Biophysical models capable of quantifying these effects may improve cancer risk
      estimation at radiation doses below the epidemiological detection threshold.
      Understanding the spatial patterns of bystander responses is important, because
      it provides estimates of how many bystander cells are affected per irradiated
      cell. In a first approach to modeling of bystander spatial effects in a three
      dimensional artificial tissue, we assume the following: (1) The bystander
      phenomenon results from signaling molecules (S) that rapidly propagate from
      irradiated cells and decrease in concentration (exponentially in the case of
      planar symmetry) as distance increases. (2) These signals can convert cells to a
      long-lived epigenetically activated state, e.g. a state of oxidative stress;
      cells in this state are more prone to DNA damage and behavior alterations than
      normal and therefore exhibit an increased response (R) for many end points (e.g.
      apoptosis, differentiation, micronucleation). These assumptions are implemented
      by a mathematical formalism and computational algorithms. The model adequately
      describes data on bystander responses in the 3D system using a small number of
      adjustable parameters.

PMID- 18088189
TI  - Fractionated, low-dose-rate ionizing radiation exposure and chronic ulcerative
      dermatitis in normal and Trp53 heterozygous C57BL/6 mice.
AB  - The influence of low-dose-rate chronic radiation exposure and adaptive responses
      on non-cancer diseases is largely unknown. We examined the effect of low-dose/low
      dose-rate fractionated or single exposures on spontaneous chronic ulcerative
      dermatitis in Trp53 normal or heterozygous female C57BL/6 mice. From 6 weeks of
      age, mice were exposed 5 days/week to single daily doses (0.33 mGy, 0.7 mGy/h)
      totaling 48, 97 or 146 mGy over 30, 60 or 90 weeks, and other Trp53+/- mice were
      exposed to a single dose of 10 mGy (0.5 mGy/min) at 20 weeks of age. The 90-week
      exposure produced an adaptive response, decreasing both disease frequency and
      severity in Trp53+/+ mice and extending the life span of older animals euthanized
      due to severe disease. The 30- or 60-week exposures had no significant protective
      or detrimental effect. In contrast, the chronic, fractionated exposure for 30 or
      60 weeks significantly increased the frequency and severity of the disease in
      older Trp53+/- mice, significantly decreasing the life span of the animals
      required to be euthanized for disease. Similarly, the single 10-mGy exposure also
      increased disease frequency in older animals. However, the chronic, fractionated
      exposure for 90 weeks prevented these detrimental effects, with disease frequency
      and severity not different from unexposed controls. We conclude that very low
      dose fractionated exposures can induce a protective adaptive response in both
      Trp53 normal and heterozygous mice, but that a lower threshold level of exposure,
      similar in both cases, must first be passed. In mice with reduced Trp53
      functionality, doses below the threshold can produce detrimental effects.

PMID- 18088190
TI  - Parthenolide sensitizes cells to X-ray-induced cell killing through inhibition of
      NF-kappaB and split-dose repair.
AB  - Human cancers have multiple alterations in cell signaling pathways that promote
      resistance to cytotoxic therapy such as X rays. Parthenolide is a sesquiterpene
      lactone that has been shown to inhibit several pro-survival cell signaling
      pathways, induce apoptosis, and enhance chemotherapy-induced cell killing. We
      investigated whether parthenolide would enhance X-ray-induced cell killing in
      radiation resistant, NF-kappaB-activated CGL1 cells. Treatment with 5 microM
      parthenolide for 48 to 72 h inhibited constitutive NF-kappaB binding and cell
      growth, reduced plating efficiency, and induced apoptosis through stabilization
      of p53 (TP53), induction of the pro-apoptosis protein BAX, and phosphorylation of
      BID. Parthenolide also enhanced radiation-induced cell killing, increasing the X
      ray sensitivity of CGL1 cells by a dose modification factor of 1.6. Flow
      cytometry revealed that parthenolide reduced the percentage of X-ray-resistant S
      phase cells due to induction of p21 waf1/cip1 (CDKN1A) and the onset of G1/S and
      G2/M blocks, but depletion of radioresistant S-phase cells does not explain the
      observed X-ray sensitization. Further studies demonstrated that the enhancement
      of X-ray-induced cell killing by parthenolide is due to inhibition of split-dose
      repair.

PMID- 18088195
TI  - Fast-acting antidepressants: are we nearly there?

PMID- 18088197
TI  - Galantamine in Alzheimer's disease.
AB  - Galantamine is a cholinesterase inhibitor with a dual mechanism of action. It is
      a reversible inhibitor of acetylcholine esterase and enhances the intrinsic
      action of acetylcholine on nicotinic receptors, leading to increased cholinergic
      neurotransmission in the CNS. Galantamine has a large volume clearance, low
      plasma protein binding and a high bioavailability. Short-term, double-blind,
      placebo-controlled studies have shown that treatment with galantamine produces
      small improvements on cognitive tests and global measures of change in selected
      patients with mild to moderately severe Alzheimer's disease. A dose of 16-24
      mg/day appears to be the most efficacious, and is the licensed maintenance dose
      range in most territories. The magnitude of the treatment effect is similar to
      that of other cholinesterase inhibitors. Adverse events experienced by patients
      treated with galantamine are usually mild, gastrointestinal and may improve with
      dose reduction.

PMID- 18088198
TI  - Depersonalization disorder: pharmacological approaches.
AB  - Depersonalization disorder (DPD) is a chronic and distressing condition with a
      prevalence in the general population between 0.8 and 2%. Several neurobiological
      studies in the last decade have shown that patients have suppressed limbic
      activation to emotional stimuli. Such findings are in line with a model which
      suggests that the condition is generated by an anxiety-triggered, 'hard-wired'
      inhibitory response to threat. Such a mechanism would ensure the preservation of
      adaptive behavior, during situations normally associated with overwhelming and
      potentially disorganizing anxiety. In DPD, such a response would become chronic
      and dysfunctional. Depersonalization remains a condition for which no definitive
      treatment exists, and for which conventional medications, such as antidepressants
      or antipsychotics, have been found to be of little value. Fortunately, a few
      promising lines of pharmacological treatment have emerged in recent years,
      although more rigorous studies are needed. For example, a number of studies
      suggest that opioid receptor antagonists such as naltrexone and naloxone are
      useful in at least a subgroup of patients. In spite of initial expectations, the
      use of lamotrigine as a sole medication has not been found useful. However, open
      label trials suggest that its use as an add-on treatment with selective serotonin
      reuptake inhibitors (SSRIs) is beneficial in a substantial number of patients.
      Similarly, the use of clonazepam, particularly in conjunction with SSRI
      antidepressants, appears to be beneficial in patients with high levels of
      background anxiety. In line with the stress-related model of depersonalization,
      those neurotransmitter systems of relevance to depersonalization are known to
      play important inhibitory roles in the regulation of the stress response.

PMID- 18088199
TI  - CBT for the treatment of depression in Parkinson's disease: a promising
      nonpharmacological approach.
AB  - Depression is very common in Parkinson's disease (PD) and linked with a faster
      progression of physical symptoms, greater cognitive decline and poorer quality of
      life. Nonpharmacological approaches, such as cognitive-behavioral therapy (CBT),
      for the treatment of depression in PD (dPD) have received little experimental
      attention despite strong demonstrated efficacy in other geriatric and medical
      populations. Depressed PD patients often differ from the depressed non-PD elderly
      in that they present with increased rates of both executive dysfunction and
      comorbid psychiatric diagnoses, may differ in their depressive symptom
      presentation and typically have caregivers who are highly involved in their
      treatment. Therefore, it is not possible to conclude that empirically validated
      treatments in the depressed aged will generalize to those with PD. In order to be
      most effective for PD patients, CBT should be tailored to their unique needs.
      Additional controlled research is needed to further explore the efficacy of CBT
      for dPD.

PMID- 18088200
TI  - Cannabinoids as potential new therapy for the treatment of gliomas.
AB  - Gliomas constitute the most frequent and malignant primary brain tumors. Current
      standard therapeutic strategies (surgery, radiotherapy and chemotherapeutics,
      e.g., temozolomide, carmustin or carboplatin) for their treatment are only
      palliative and survival diagnosis is normally 6-12 months. The development of new
      therapeutic strategies for the management of gliomas is therefore essential.
      Interestingly, cannabinoids have been shown to exert antiproliferative effects on
      a wide spectrum of cells in culture. Of interest, cannabinoids have displayed a
      great potency in reducing glioma tumor growth either in vitro or in animal
      experimental models, curbing the growth of xenografts generated by subcutaneous
      or intratecal injection of glioma cells in immune-deficient mice. Moreover,
      cannabinoids appear to be selective antitumoral agents as they kill glioma cells
      without affecting the viability of nontransformed counterparts. A pilot clinical
      trial on patients with glioblastoma multiforme demonstrated their good safety
      profile together and remarkable antitumor effects, and may set the basis for
      further studies aimed at better evaluating the potential anticancer activity of
      cannabinoids.

PMID- 18088201
TI  - Assessment and treatment of suicide risk in schizophrenia.
AB  - Schizophrenic patients at risk of suicide are more likely to be young, male,
      white, never married, with post-psychotic depression, and a history of substance
      abuse and suicide attempts. Hopelessness, social isolation, awareness of illness
      and hospitalization are also related to suicide risk. Deteriorating health with a
      high level of premorbid functioning, recent loss or rejection, limited external
      support, family stress or instability are other features that have been reported
      in schizophrenic patients who commit suicide. Atypical antipsychotics, especially
      clozapine, have emerged as important tools in the therapeutic armamentarium.
      Psychosocial intervention and psychotherapy may play an important role in the
      management of suicide risk, especially if such interventions help the patient
      face daily difficulties, loneliness and conflicts inside the family.

PMID- 18088202
TI  - Post-stroke depression.
AB  - Post-stroke depression (PSD) is among the most common emotional disorders
      afflicting stroke sufferers. Approximately one third of stroke survivors
      experience an early or later onset of depression. PSD impedes the rehabilitation
      and recovery process, jeopardizes quality of life and increases mortality.
      Diagnosis of PSD is challenging in the acute and chronic aftermath. Therefore, it
      often remains unrecognized and/or undertreated. The interaction between
      depression and stroke is very complex and the pathophysiological mechanisms have
      not as yet been fully elucidated, although an interaction between anatomical and
      psychosocial factors may be important in PSD development. Neurochemical changes
      and clinical findings are similar to endogenous depression. PSD is potentially
      treatable, although no conclusive benefits of antidepressant agents and
      nonpharmacological interventions have been observed. The efficacy of preventive
      strategies in PSD remains essentially undetermined.

PMID- 18088203
TI  - Neurobiology of bipolar disorder.
AB  - Bipolar disorder is one of the most severely debilitating of all medical
      illnesses. It can lead to significant suffering for patients and their families,
      limit functioning and workplace productivity, and with its risks of increased
      morbidity and mortality, it is increasingly recognized as a major public health
      problem. For a large number of patients, outcomes are poor. Patients with bipolar
      disorder generally experience high rates of relapse, a chronic recurrent course,
      lingering residual symptoms, functional impairment, psychosocial disability and
      diminished well-being. Despite this, little is known about the specific
      pathophysiology of bipolar disorder. A better understanding of the
      neurobiological underpinnings of this condition, informed by preclinical and
      clinical research, will be essential for the future development of specific
      targeted therapies that are more effective, achieve their effects more quickly
      and are better tolerated than currently available treatments. An abundance of
      research has implicated specific neuroendocrine, neurotransmitter and
      intracellular signaling systems in the pathophysiology and treatment of this
      illness. More recently, genetic association studies have identified numerous
      genes that confer vulnerability to the disorder, many of which are known to
      function in the signaling pathways previously identified as relevant to the
      etiology of the illness. In this article, we will review current knowledge
      regarding the neurotransmitter systems, signaling networks, neuroendocrine
      systems and genetics of bipolar disorder; all of these allow insight into the
      mechanism of illness and thus offer potential novel directions for the
      development of novel therapeutics.

PMID- 18088204
TI  - The serotonin transporter gene and effectiveness of SSRIs.
AB  - The definition of a genetic liability profile for specific antidepressant
      treatment will soon be available, offering considerable help in early detection
      of effective therapy in mood disorders. The search for genetic factors
      predisposing to drug response or side effects in mood disorders started only in
      the last few years. The efficacy of antidepressant action was associated with
      several polymorphisms, located on coding genes of proteins thought to be involved
      in the different mechanisms of action of antidepressant treatments. Among these,
      gene variants in sequences of serotonin pathway proteins were candidates, both
      for the well-known evidence of its involvement in the development of depressive
      symptoms and for the worldwide use of selective serotonin reuptake inhibitors as
      first-choice treatment of depression. A polymorphism in the promoter region of
      the serotonin transporter (SERTPR) was independently associated with efficacy for
      a range of treatments. This article reviews the pharmacogenetic studies published
      to date, focusing the attention on the SERTPR.

PMID- 18088205
TI  - Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy in
      pediatric brain tumors.
AB  - Brain tumors are the most common solid tumor in childhood. Surgery and/or
      fractionated radiotherapy are conventional treatment modalities. Stereotactic
      radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) are advanced
      radiation therapy techniques that have been frequently used in adults with brain
      tumors but they are less frequently used in pediatric patients. SRS and FSRT can
      potentially add to the armamentarium against brain tumors in children. This
      article will review the role of SRS and FSRT in the management of pediatric brain
      tumors.

PMID- 18088206
TI  - Lifestyle-related factors in predementia and dementia syndromes.
AB  - Cognitive decline and dementia have a deep impact on the health and quality of
      life of older subjects and their caregivers. Since the therapeutic options
      currently available have demonstrated limited efficacy, the search for preventive
      strategies for cognitive decline and dementia are mandatory. A possible role of
      lifestyle-related factors was recently proposed for age-related changes of
      cognitive function, predementia syndromes and the cognitive decline of
      degenerative (Alzheimer's disease [AD]) or vascular origin. At present,
      cumulative evidence suggests that vascular risk factors may be important in the
      development of mild cognitive impairment (MCI), dementia and AD. Moderate alcohol
      drinking has been proposed as a protective factor against MCI and dementia in
      several longitudinal studies, but contrasting findings also exist. The
      Mediterranean diet could therefore be an interesting model with which to further
      study the association between dietary patterns and cognitive functioning, given
      the suggested role of many components of this diet (monounsaturated fatty acids,
      polyunsaturated fatty acids, cereals and red wine) in contrasting cognitive
      impairment and dementia. The association between low education and predementia
      and dementia syndromes is supported by the majority of studies, but very few
      studies have investigated whether this association may be attributed with
      lifestyle factors that covary with education. Studies in the literature seem to
      identify in physical exercise one promising strategy in decreasing cognitive
      decline, but some of the limitations of these studies do not allow us to draw
      definite conclusions. At present, in older subjects, healthy diets, antioxidant
      supplements, the prevention of nutritional deficiencies, and moderate physical
      activity could be considered the first line of defense against the development
      and progression of predementia and dementia syndromes. However, in most cases,
      these were only observational studies, and results are awaited from large
      multicenter randomized clinical trials in older persons that may clarify the
      possible synergy, for example, between moderate exercise, physical activity and
      healthy Mediterranean diet on cognition in the elderly.

PMID- 18088207
TI  - Introduction to the special section on adolescent romantic competence:
      development and adjustment implications.
AB  - Romantic relationships are a normative developmental experience in adolescence.
      Although many prominent developmental theories recognize their importance in
      helping to form the foundations for future healthy adult relationships, empirical
      research has not progressed at an expected pace, and there remain many gaps in
      our knowledge base. Existing research suggests that, regardless of their
      duration, adolescent romances are salient emotional experiences with significant
      adjustment implications, both positive and negative. With contributions from both
      developmental and clinical researchers, the five articles in this special section
      introduce the romantic competence construct and describe some different avenues
      of investigation into its definition, measurement, and adjustment implications.
      It is our hope that these articles add to the existing knowledge base and
      stimulate interest in the romantic competence construct among clinical child and
      adolescent researchers.

PMID- 18088208
TI  - Girl friend, boy friend, girlfriend, boyfriend: broadening our understanding of
      heterosocial competence.
AB  - Heterosocial interactions, or social interactions with other-sex peers, are
      theorized to serve a number of unique developmental functions for adolescents
      (e.g., companionship, intimacy, experimentation with sex-role behaviors and
      sexual activity). Yet despite the importance of heterosocial competence in
      adolescent social development, there exists little research on the construct.
      Early research, although informative, reflects a narrow focus on heterosocial
      anxiety associated with date initiation situations. More recent research has
      broadened its purview to include investigations of the relation of heterosocial
      competence to the normative development of romantic relationships, as well as
      depression, anxiety, and violence in adolescent relationships. To facilitate
      further research, an expanded, well-defined description of the construct of
      adolescent heterosocial competence is needed that includes other-sex interactions
      in casual relationships, friendships, and romantic relationships. In this article
      we detail the historical and current definitions of the construct and encourage a
      broader understanding in the context of the developmental psychopathology
      framework. We follow with a review of our decade-long efforts to better
      operationally define and assess the construct by summarizing the development and
      validation of two measures: The Measure of Adolescent Heterosocial Competence and
      the Measure of Adolescent Heterosocial Competence-Young Adult Version. Finally,
      we suggest directions for future research.

PMID- 18088209
TI  - Perceived romantic competence, importance of romantic domains, and psychosocial
      adjustment.
AB  - This study investigated romantic competence during late adolescence, including
      preliminary psychometric properties of a new measure and its concurrent
      association with psychosocial adjustment. Six aspects of perceived romantic
      competence (romantic appeal, sexual competence, communication with partners,
      maintenance of relationships, establishing equivalent power balance in
      relationships, and feeling accepted by romantic partners) were hypothesized to
      predict unique variance in psychosocial adjustment. Self-report data were
      collected from 586 college students, a primarily female and European American
      sample. Results revealed that four domains predicted variance in psychosocial
      functioning. In addition, participants' valuing of both maintaining romantic
      relationships and positive partner characteristics moderated the effects of
      perceived competence on self-worth.

PMID- 18088210
TI  - Correlates of false self in adolescent romantic relationships.
AB  - The goal of this study was to examine the association between interpersonal
      competencies in the peer domain and feelings of false self in romantic
      relationships. Participants included 238 White, middle-class boys and girls
      (Grades 10 and 11). Students completed self report measures of false self in
      romantic relationships and interpersonal competency in same-sex and other-sex
      peer relationships. Results indicate that boys experience higher levels of false
      self in romantic relationships when compared to girls. Conflict management in the
      context of other-sex peer relationships was negatively associated with feelings
      of false self in romantic relationships for both boys and girls. For girls,
      competency in the domain of emotional support in same-sex peer relationships was
      associated with lower levels of false self in romantic relationships. For boys,
      competency in the domains of self-disclosure and asserting influence with same
      sex peers was associated with lower levels of false self in romantic
      relationships.

PMID- 18088212
TI  - Commentary: defining and understanding adolescent romantic competence: progress,
      challenges, and implications.
AB  - Commentary on the articles in this special section is provided. Following a brief
      review of the articles in this section, discussion focuses on the
      conceptualization of adolescent romantic competence, the importance of studying
      competence, and the implications of research in this area for knowing how to help
      young people have more successful romantic relationships.

PMID- 18088211
TI  - Adolescents' anxiety in dating situations: the potential role of friends and
      romantic partners.
AB  - This study examined adolescents' interpersonal functioning, including the
      qualities of their closest friendships and romantic relationships, as predictors
      of dating/heterosocial anxiety. An ethnically diverse sample of 781 adolescents
      (57% girls; ages 15-19 years) completed measures that assessed the number and
      type of close friends, the presence of a romantic relationship, the qualities of
      their best same-sex friendship and their romantic relationship (using the Network
      of Relationships Inventory-Revised), and levels of dating or heterosocial anxiety
      (using the Dating Anxiety Scale for Adolescents). Most adolescents were
      romantically involved, and girls were more likely to have a romantic partner than
      boys. Adolescents with fewer other-sex friends and those with less positive and
      more negative interactions with their best friends reported high levels of dating
      anxiety. In addition, adolescents who reported never having a romantic
      relationship, who did not have a current romantic partner, and who had less
      positive and more negative interactions with their romantic partners reported
      higher levels of dating anxiety. Variations were noted for different aspects of
      dating anxiety. The findings indicate that multiple aspects of adolescents'
      social relations may be independently and uniquely related to feelings of
      distress in dating or heterosocial situations. Adolescents' social relationships
      have the potential to support or interfere with the development of successful
      romantic relationships.

PMID- 18088213
TI  - Interpersonal behavior, psychopathology, and relationship outcomes among
      adolescent mothers and their partners.
AB  - This study was designed to identify predictors of relationship outcomes among 179
      young (ages 14-24) coparenting couples during the transition to parenthood, with
      a particular focus on interpersonal process and psychopathology. Findings
      indicated that couples identified as hostile during the prenatal assessment were
      more likely to report relationship violence at follow-up (2 years postbirth).
      Couples identified as warm were more likely to remain together as coparents even
      if their romantic relationship dissolved. Couples in which the female partner was
      highly controlling were less likely to be cohabiting at follow-up. Mothers with a
      history of substance abuse and fathers with a history of conduct disorder were
      also more likely to engage in interpartner violence. Latino couples were more
      likely than Caucasian and African American couples to be warmly engaged and to
      remain romantically involved across the transition to parenthood.

PMID- 18088214
TI  - The invisible bonds: does the secure base script of attachment influence
      children's attention toward their mother?
AB  - The internal working model of attachment can be conceptualized as a cognitive
      schema to provide testable hypotheses. Thus, this study predicts a relationship
      between attachment and attentional bias toward the mother using an emotional
      modification of the exogenous cueing task. The content of the cues (mother vs.
      unknown women) and the duration of the presentation of the cues (200 msec vs.
      1,000 msec) were varied. The test was administered to 40 nonreferred children (9
      to 13 years of age), divided into high- and low-secure attachment groups. As
      predicted, low-secure children directed their attention more quickly toward
      mother than toward unknown women at later stages of attentional processing (long
      presentation), Furthermore, low-secure children showed more maintained attention
      toward mother compared to unknown women and showed significantly more maintained
      attention toward mother compared with high-secure children.

PMID- 18088215
TI  - Threat perception bias and anxiety among Chinese school children and adolescents.
AB  - This study evaluated the relationship between threat perception bias and anxiety
      among children and adolescents in China. A sample of 1,004 elementary, middle and
      high school students aged 9 to 19 years listened to stories containing themes of
      generalized anxiety, social anxiety and separation anxiety in either an ambiguous
      or non-ambiguous context. The story content included topics such as upset
      stomach, teacher-student interaction, and parents who are late to return home.
      Multiple threat perception indices were derived from children's responses.
      Children's level of anxiety was assessed by means of self-report questionnaires
      and parental reports. Higher levels of anxiety were related to higher frequencies
      of threat perception and interpretation, lower thresholds to detect threat and
      more negative feelings and cognitions. Age and gender were also related to some
      indices of threat perception bias. Threat perception bias was related to anxious
      symptomatology in general and was not content specific to particular anxiety
      disorders. The findings were consistent with studies conducted in Western culture
      and suggest that cognitive processing theories of childhood anxiety may
      generalize beyond Western society.

PMID- 18088216
TI  - Implementing CBT for traumatized children and adolescents after september 11:
      lessons learned from the Child and Adolescent Trauma Treatments and Services
      (CATS) Project.
AB  - The Child and Adolescent Trauma Treatments and Services Consortium (CATS) was the
      largest youth trauma project associated with the September 11 World Trade Center
      disaster. CATS was created as a collaborative project involving New York State
      policymakers; academic scientists; clinical treatment developers; and routine
      practicing clinicians, supervisors, and administrators. The CATS project was
      established to deliver evidence-based cognitive-behavioral trauma treatments for
      children and adolescents affected by the September 11 terrorist attack in New
      York City and to examine implementation processes and outcomes associated with
      delivery of these treatments. Referrals were obtained on 1,764 children and
      adolescents; of these, 1,387 were subsequently assessed with a standardized
      clinical battery and 704 found to be eligible for services. Ultimately 700 youth
      participated in the project. Treatments were delivered in either school or clinic
      settings by clinicians employed in 9 provider organizations in New York City. All
      participating clinicians were trained on the cognitive behavioral therapy models
      by the treatment developers and received case consultation for 18 months by
      expert clinician consultants and the treatment developers. The challenges of
      mounting a large trauma treatment project within routine clinical practices in
      the aftermath of a disaster and simultaneously evaluating the project have been
      significant. We outline the major challenges, describe strategies we employed to
      address them, and make recommendations based on critical lessons learned.

PMID- 18088217
TI  - Mothers' parenting dimensions and adolescent externalizing and internalizing
      behaviors in a low-income, urban Mexican American sample.
AB  - The relation between adolescent-reported parenting behaviors and mother-reported
      youth externalizing and internalizing behaviors was examined among 91 Mexican
      American mother-adolescent (ages 13-17) dyads recruited from an immigrant enclave
      in a large midwestern metropolitan area. Two major dimensions of mothers'
      parenting emerged: supportive parenting and harsh parental control. Gender
      moderation analyses revealed that lower levels of externalizing behaviors were
      linked with mothers' higher levels of supportive parenting among girls but not
      among boys. Higher levels of youth-reported depression were linked with mothers'
      higher levels of harsh parental control among boys but not among girls. The
      findings highlight the importance of supportive parenting and of gender in the
      study of Mexican American families and youth mental health.

PMID- 18088218
TI  - Enhancing a classroom social competence and problem-solving curriculum by
      offering parent training to families of moderate- to high-risk elementary school
      children.
AB  - The Incredible Years parent and classroom interventions were evaluated for the
      first time in elementary schools. Culturally diverse, socioeconomically
      disadvantaged schools were randomly assigned to intervention or control (CON). In
      intervention schools, all children received a 2-year classroom intervention
      beginning in kindergarten. In addition, indicated children were randomly assigned
      to also receive parent training (PT + CR) or only the classroom intervention
      (CR). PT + CR mothers reported that, following intervention, children showed
      fewer externalizing problems and more emotion regulation than CR or CON children.
      Observations showed that child-mother bonding was stronger in the PT + CR
      condition than in the CON condition, and PT + CR mothers were significantly more
      supportive and less critical than CR or CON mothers. Teachers reported that PT +
      CR mothers were significantly more involved in school and that children in the PT
      + CR and the CR conditions had significantly fewer externalizing problems than in
      the CON condition.

PMID- 18088219
TI  - The situation specificity of youth responses to peer provocation.
AB  - Previous studies have identified peer provocation as a challenging class of
      situations for youth. The work presented here builds on previous methods of
      assessing peer provocation by (a) increasing the contextual detail of the
      vignettes; (b) developing a reliable, descriptive coding system of the range of
      youth responses to physical, verbal, and relational provocation; and (c)
      assessing the relevance of these situations for a sample (N = 76) of ethnically
      diverse, economically disadvantaged youth ages 12 to 14. The vignettes were used
      to examine the situation specificity of youth responses to provocation. Situation
      and identity of aggressor were both predictors of youth responses. For example,
      participants "matched" physical aggression to physical provocation. These
      findings are consistent with previous studies demonstrating the situation
      specificity of social information processing, even within the relatively
      homogeneous category of peer provocations.

PMID- 18088220
TI  - Effects of methylphenidate and behavior modification on the social and academic
      behavior of children with disruptive behavior disorders: the moderating role of
      callous/unemotional traits.
AB  - This study examined whether response to behavior modification with and without
      methylphenidate differed for children with attention-deficit/hyperactivity
      disorder (ADHD) and conduct problems (CP) depending on the presence of
      callous/unemotional (CU) traits. Participants were 37 children ages 7 to 12,
      including 19 with ADHD/CP-only and 18 with ADHD/CP-CU, referred to a university
      based summer treatment program. Results showed that ADHD/CP-CU children had worse
      behavior in the behavior-therapy-only (BT-only) condition, especially on measures
      of CP, noncompliance, and rule violations, but these differences largely
      disappeared when medication was added to BT. Children with ADHD/CP-CU were also
      less likely to be normalized by treatment than were children with ADHD/CP-only.
      These findings, though tentative, suggest that children with ADHD/CP-CU may not
      show a sufficient positive response to BT alone and that the combination of
      medication and BT may be especially important for them.

PMID- 18088221
TI  - Functional impairment in childhood OCD: development and psychometrics properties
      of the Child Obsessive-Compulsive Impact Scale-Revised (COIS-R).
AB  - This article documents the development, factor structure, and psychometric
      properties of the parent- and youth-report forms of the Child Obsessive
      Compulsive Impact Scale-Revised (COIS-R), a measure of obsessive-compulsive
      disorder (OCD)-specific functional impairment. Using a sample of 250 youth (M age
      = 11.7, 54% male, 80% Caucasian) diagnosed with OCD in a university hospital
      based child anxiety clinic, exploratory factor analysis was employed to develop a
      4-factor structure for the parent-report measure (Daily Living Skills, School,
      Social, Family/Activities) and a 3-factor structure for the youth-report form
      (School, Social, Activities). Both measures demonstrated good internal
      consistency, concurrent validity, and test-retest reliability. Moreover, partial
      correlations demonstrated significant associations between COIS-R scales and
      clinician global assessment of functioning scores controlling for both symptom
      severity and comorbid internalizing and externalizing symptomatology. These
      findings suggest that the COIS-R may hold utility for assessing the specific
      impact of OCD symptoms on youth functioning.

PMID- 18088223
TI  - The use of the coping power program to treat a 10-year-old girl with disruptive
      behaviors.
AB  - This article describes the successful application of the Coping Power program by
      school-based clinicians to address a 10-year-old girl's disruptive behavior
      symptoms. Coping Power is an empirically supported cognitive-behavioral program
      for children at risk for serious conduct problems and their parents. The
      following case study illustrates the core features of the Coping Power child and
      parent components while describing the use of assessment data and clinical
      decision making during the implementation of a manualized intervention.

PMID- 18088222
TI  - A brief taxometrics primer.
AB  - Taxometric procedures provide an empirical means of determining which psychiatric
      disorders are typologically distinct from normal behavioral functioning. Although
      most disorders reflect extremes along continuously distributed behavioral traits,
      identifying those that are discrete has important implications for accurate
      diagnosis, effective treatment, early identification of risk, and improved
      understanding of etiology. This article provides (a) brief descriptions of the
      conceptual bases of several taxometric procedures, (b) example analyses using
      simulated data, and (c) strategies for avoiding common pitfalls that are often
      observed in taxometrics research. To date, most taxometrics studies have appeared
      in the adult psychopathology literature. It is hoped that this primer will
      encourage interested readers to extend taxometrics research to child and
      adolescent populations.

PMID- 18088224
TI  - The mystery of human papillomaviruses in carcinogenesis.

PMID- 18088226
TI  - 1,5-anhydroglucitol (GlycoMark) as a marker of short-term glycemic control and
      glycemic excursions.
AB  - 1,5-anhydroglucitol (1,5-AG) is a validated marker of short-term glycemic
      control. It is a metabolically inert polyol that competes with glucose for
      reabsorption in the kidneys. Otherwise stable levels of 1,5-AG are rapidly
      depleted as blood glucose levels exceed the renal threshold for glucosuria. 1,5
      AG more accurately predicts rapid changes in glycemia than hemoglobin A1C (A1C)
      or fructosamine. It is also more tightly associated with glucose fluctuations and
      postprandial glucose. Thus, 1,5-AG may offer complementary information to A1C.
      This review will summarize the limitations of current methods of assessing
      glycemic control, assess the data to support 1,5-AG as a glycemic marker and
      highlight the scenarios by which 1,5-AG may fill the gap in assessing glycemic
      control.

PMID- 18088227
TI  - Practical utility of urinary assay in the diagnosis of Alzheimer's disease:
      AlzheimAlert.
AB  - Urinary assay (Alzheimer's disease reaction titer [ADRT]) adds significant
      information in the diagnosis of Alzheimer's disease (AD), particularly for the
      nonspecialist. Clinical studies of ADRT in series of AD and non-AD patients have
      found sensitivity of 89-92.3%, specificity of 90-96.8%, positive predictive value
      (PPV) of 94.8-97.4% and negative predictive value (NPV) of 78.9-91.8%. The added
      information from the improvements of PPV and NPV are particularly helpful for the
      nonspecialist in the community. As a laboratory assay that requires a first
      morning noncontaminated sample, ADRT is noninvasive, convenient and safe. ADRT is
      based on reagents derived from human AD brain cDNA. The pathophysiological roles
      of these genetic fragments and reagents are still under investigation. ADRT
      should have a positive impact on primary-care AD clinical practice.

PMID- 18088228
TI  - Innovative genomic-based model for personalized treatment of gastric cancer:
      integrating current standards and new technologies.
AB  - In the era of network biology, understanding the complexity of the signaling
      pathways network in cancer origin, progression and metastasis will dramatically
      alter and improve treatment strategies. Prognosis of gastric cancer remains poor.
      Clinical decisions on treatment are based on tumor-node-metastasis (TNM) staging,
      but are suboptimal. This perspective review, integrating several concepts,
      including cancer stem cells, provides a novel treatment model for tailoring the
      best treatment in individual patients with gastric cancer. Biologic metastatic
      steps (invasion, angiogenesis, intra/extravasation, colonization and
      microenvironment at distant organs) are orchestrated by mutated genes.
      Identifying and profiling these key genes and their interactions with
      environmental factors such as Helicobacter pylori, driver mutations and
      interacting signaling pathways using high-throughput technologies (including
      omics, resequencing, genome-wide associations studies and RNAi) in unbiased
      studies can lead to the development of both novel biomarkers and targeted agents.
      A comprehensive bench-to-bedside treatment-guided algorithm is provided for
      optimum preoperative or postoperative combination of cytotoxic and targeted
      agents. The protocol can be applied with adequate modification for most solid
      tumors.

PMID- 18088229
TI  - Methods for routine diagnosis of genomic rearrangements: multiplex PCR-based
      methods and future perspectives.
AB  - Germline and somatic genomic rearrangement play a relevant role in the
      pathogenesis of genetic disorders, and their identification is a fundamental task
      in molecular diagnosis. However, screening for structural genomic abnormalities
      is often not included in routine mutational analyses and consequently the
      proportion of rearrangements playing a pathogenic role in several genetic
      disorders is likely to be underestimated. A wide range of molecular techniques
      for the detection of large genomic rearrangements has been developed: some
      methods have the power to screen the whole genome, others are designed to analyze
      one or few loci that are known to be involved in a specific disease; some may
      detect balanced rearrangements, while others only unbalanced rearrangements; some
      are suitable for detection of germline abnormalities, yet others also detect
      somatic abnormalities. This review provides a brief summary of principles,
      applications and limitations of the methods available for the screening of
      genomic rearrangements, focusing on multiplex PCR-based protocols that are
      currently employed in routine detection of extended germline genomic deletions or
      duplications. Future developments based on microarray platforms and high
      throughput sequencing are also discussed.

PMID- 18088230
TI  - Proteomics in leptospirosis research: towards molecular diagnostics and vaccine
      development.
AB  - Leptospirosis is a bacterial zoonotic disease that remains a public health
      problem worldwide. Unfortunately, the current gold standard test used for the
      serological diagnosis of leptospirosis has some drawbacks and there is no vaccine
      available for successful prevention of leptospirosis in humans. Therefore, recent
      research on leptospirosis has focused mainly on identifying leptospiral
      immunogens to be used for diagnostics and vaccine development. This review
      provides a brief summary of recent proteomic studies applied to leptospirosis.
      These studies were conducted with two major aims: to characterize outer membrane
      proteins using a classical proteomics approach and to identify potential
      leptospiral immunogens using an immunoproteomics approach. The results obtained
      from these studies may lead to the development of earlier and more accurate
      diagnostic test(s) and vaccine discovery.

PMID- 18088231
TI  - Biological markers in the diagnosis of recurrent bladder cancer: an overview.
AB  - Over the last years, many biological markers emerged that act as an adjunct for
      the detection of early bladder cancer recurrence. Some of these markers had a
      proven better sensitivity and specificity for cancer detection than urine
      cytology. Nevertheless, the majority of these biological makers are still in
      advanced stages of clinical trials and are not used for routine clinical
      purposes. In this article, we give an overview on the biological markers that can
      play a role in early bladder cancer detection and can perhaps subsequently reduce
      the need for frequent cystoscopies.

PMID- 18088232
TI  - Stat5 as a diagnostic marker for leukemia.
AB  - The Jak-Stat-Socs pathway is an important component of cytokine receptor
      signaling. Not surprisingly, perturbation of this pathway is implicated in
      diseases of hematopoietic and immune origin, including leukemia, lymphoma and
      immune deficiencies. This review examines the role of a key component of this
      pathway, Stat5. This has been shown to be activated in a variety of leukemias and
      myeloproliferative disorders, including downstream of a range of key oncogenes
      where it has been shown to play an important role in mediating their effects.
      Therefore, Stat5 represents a useful pan-leukemia/myeloproliferative disorder
      diagnostic marker and key therapeutic end point, as well as representing an
      attractive therapeutic target for these disorders.

PMID- 18088233
TI  - Molecular genetics of thyroid cancer: implications for diagnosis, treatment and
      prognosis.
AB  - Thyroid cancer is the most common malignant tumor of the endocrine system and
      accounts for approximately 1% of all newly diagnosed cancer cases. The most
      frequent type of thyroid malignancy is papillary carcinoma, which constitutes
      approximately 80% of all cases. Papillary carcinomas frequently have genetic
      alterations leading to the activation of the MAPK signal pathway. Those include
      RET/PTC rearrangement and point mutations of the BRAF and RAS genes. Mutations in
      these genes are found in over 70% of papillary carcinomas and they rarely overlap
      in the same tumor. Frequent genetic alterations in follicular carcinomas, the
      second most common type of thyroid malignancy, include RAS mutations and PAX8
      PPAR gamma rearrangement. RET point mutations are crucial for the development of
      medullary thyroid carcinomas. Many of these mutations, particularly those leading
      to the activation of the MAPK pathway, are being actively explored as therapeutic
      targets for thyroid cancer. Detection of these genetic alterations using
      molecular techniques is important for preoperative fine-needle aspiration
      diagnosis, prognosis and treatment of thyroid cancer.

PMID- 18088234
TI  - Ewing sarcoma family of tumors: a model for the new era of integrated laboratory
      diagnostics.
AB  - The Ewing sarcoma family of tumors (ESFT) represents one of the best models
      illustrating the multifaceted approach to the diagnosis of cancer that has
      evolved over the past decade. ESFT encompasses tumors that arise in bone or soft
      tissues and may have disparate histologic features. As a result, it was not until
      the discovery that these tumors share a common underlying molecular pathogenesis
      (chromosomal translocations involving the EWS gene and one of several members of
      the ETS family of transcription factors) that significant advances in the
      diagnosis and therapy of ESFT became possible. As a result, ESFT has come to
      embody the amalgamation of classical diagnostic tools, such as histology and
      routine microscopy, with newer techniques, such as immunohistochemistry and
      molecular techniques; the latter include PCR-based methods and fluorescence in
      situ hybridization. This review will address the features of ESFT and how it has
      emerged as a model for the new era of integrated diagnostics.

PMID- 18088235
TI  - The promise of PET in clinical management and as a sensitive test for drug
      cytotoxicity in sarcomas.
AB  - Positron emission tomography (PET) is a noninvasive functional imaging technique
      that allows assessment of key biological processes important in cancer
      development and progression. It provides information complementary to
      conventional anatomic imaging, demonstrating utility in a range of cancer
      settings from diagnosis, biopsy guidance, tumor stratification and
      prognostication, and staging and surveillance of disease recurrence. Its ability
      to evaluate vital processes in tumor biology also makes it a potentially valuable
      and sensitive tool for assessing therapeutic response. The development of novel
      PET tracers and improvements in technology will only continue to augment the
      potential of PET and enhance its attractiveness as an instrument to facilitate
      drug development. This article will discuss the above issues, using the setting
      of sarcomas as an example.

PMID- 18088236
TI  - Anti-(apolipoprotein A-1) IgGs are associated with high levels of oxidized low
      density lipoprotein in acute coronary syndrome.
AB  - ApoA-1 (apolipoprotein A-1) is the main component of HDL (high-density
      lipoprotein) and stabilizes PON-1 (paraoxonase-1), which prevents lipid
      peroxidation and oxLDL (oxidized low-density lipoprotein) formation.
      Autoantibodies against apoA-1 [anti-(apoA-1) IgG] have been found in
      antiphospholipid syndrome and systemic lupus erythematosous, two diseases with an
      increased risk of thrombotic events, as well as in ACS (acute coronary syndrome).
      OxLDL levels are also elevated in these diseases. Whether anti-(apoA-1) IgGs
      exist in other prothrombotic conditions, such as APE (acute pulmonary embolism)
      and stroke, has not been studied and their potential association with oxLDL and
      PON-1 activity is not known. In the present study, we determined prospectively
      the prevalence of anti-(apoA-1) IgG in patients with ACS (n=127), APE (n=58) and
      stroke (n=34), and, when present, we tested their association with oxLDL levels.
      The prevalance of anti-(apoA-1) IgG was 11% in the ACS group, 2% in the control
      group and 0% in the APE and stroke groups. The ACS group had significantly higher
      median anti-(apoA-1) IgG titres than the other groups of patients. Patients with
      ACS positive for anti-(apoA-1) IgG had significantly higher median oxLDL values
      than those who tested negative (226.5 compared with 47.7 units/l; P<0.00001) and
      controls. The Spearman ranked test revealed a significant correlation between
      anti-(apoA-1) IgG titres and serum oxLDL levels (r=0.28, P<0.05). No association
      was found between PON-1 activity and oxLDL or anti-(apoA-1) IgG levels. In
      conclusion, anti-(apoA-1) IgG levels are positive in ACS, but not in stroke or
      APE. In ACS, their presence is associated with higher levels of oxLDL and is
      directly proportional to the serum concentration of oxLDL. These results
      emphasize the role of humoral autoimmunity as a mediator of inflammation and
      coronary atherogenesis.

PMID- 18088238
TI  - Old and emerging therapies in chronic hepatitis C: an update.
AB  - The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a
      sustained virological response currently defined as undetectable HCV-RNA in
      peripheral blood determined with the most sensitive polymerase chain reaction
      technique 24 weeks after the end of treatment. This goal is practically
      equivalent with eradication of HCV infection and cure of the underlying HCV
      induced liver disease. The current standard in hepatitis C treatment consists in
      combination regimens of pegylated interferon-alpha (Peg-INF-alpha) with Ribavirin
      (RBV). Such treatment schemes are quite successful in patients with HCV genotypes
      2 and 3 infections achieving HCV eradication rates of 75-90%. However, they are
      much less effective in patients with genotypes 1 and 4 infections with
      eradication rates ranging between 45% and 52%. Moreover, they have several, and
      sometimes severe, adverse effects and contraindications, further limiting their
      efficacy and applicability in an appreciable number of patients with chronic HCV
      induced liver disease. Therefore, the need for improvement of existing therapies
      and for development of new effective, safe and tolerable drugs is a matter of
      great clinical relevance and importance. In this article, recent improvements in
      the current standard of therapy with IFN-alpha and RBV in various subsets of
      patients with chronic hepatitis C and in the clinical development of new emerging
      drugs, particularly small molecules, will be reviewed and commented. The article
      is divided in two main parts: (i) improvements in the standard combination
      therapies and schemes of approved Peg-INF-alpha with RBV and expectations from
      new interferons, interferon inducers and alternatives to RBV; (ii) new drugs for
      HCV in clinical development focusing mostly on specific inhibitors of HCV and
      less so on other drugs including immune therapies.

PMID- 18088240
TI  - Waning-off effect of serum hepatitis B surface antibody amongst Taiwanese
      university students: 18 years post-implementation of Taiwan's national hepatitis
      B vaccination programme.
AB  - Hepatitis B virus (HBV) infection and its sequelae remain a major health problem
      for Taiwan. The national hepatitis B (HB) vaccination programme was first
      launched in 1984 to combat the spread of this infection. This study examined the
      status of HBV infection amongst students at a Taiwanese university in 2005, 18
      years after the implementation of a nation-wide mass HB vaccination programme. In
      2005, 5875 new university entrants, who were born during the period 1 July 1976
      to 30 June 1988, were subdivided into one of 12 one-year-interval birth-year
      cohorts. Each student was individually tested for serum hepatitis B surface
      antigen (HBsAg), Antibody to hepatitis B surface antigen (anti-HBs) and antibody
      to hepatitis B core antigen (anti-HBc) status. We observed a declining trend of
      past exposure to HB infection from 48.7% (1976 birth-year cohort) to 5.2% (1987
      birth-year cohort). The prevalence of chronic HB infection also declined from
      14.5% (1976 birth-year cohort) to 1.9% (1987 birth-year cohort). The prevalence
      of persistent HB immunity through (earlier) active vaccination declined from 72%
      (1984 birth-year cohort) to 41.6% (1987 birth-year cohort). The prevalence of HB
      infection-naive individuals increased from 18.2% (1984 birth-year cohort) to
      53.1% (1987 birth-year cohort). This study demonstrates that as the
      implementation of the mass HB vaccination programme in 1984, the incidence of HB
      infection in Taiwan has declined, although a 'waning-off' effect of serum anti
      HBs to low or undetectable levels, which may not provide protection, amongst this
      student population has arisen, 18 years following the implementation of the
      nation-wide HB vaccination programme. Such a situation may mean that these
      individuals may not be effectively protected against future HB infection. A
      booster dose of HB vaccine, given 18 years following HB vaccination, perhaps even
      earlier, should be considered.

PMID- 18088239
TI  - Underestimation of chronic hepatitis B virus infection in the United States of
      America.

PMID- 18088241
TI  - Long-term lamivudine treatment of children with chronic hepatitis B: durability
      of therapeutic responses and safety.
AB  - Lamivudine has been demonstrated safe and efficacious in the short term in a
      large cohort of children with chronic hepatitis B (CHB), but optimal duration of
      treatment has not been elucidated and limited data on the safety of long-term
      lamivudine administration have been reported. In addition, the durability of
      favourable therapeutic outcomes after lamivudine therapy in children has not been
      well characterized. The aim of this study was to examine the safety of lamivudine
      and the durability of clinical responses in a group of children who received up
      to 3 years of treatment for CHB. One hundred and fifty-one children from centres
      in nine countries who had previously received lamivudine in a large prospective
      trial were enrolled. During the first year, children had been randomized to
      either lamivudine or placebo treatment. Subsequently, in a separate extension
      study, those who remained hepatitis B e antigen (HBeAg) positive were given
      lamivudine for up to 2 years and those who were HBeAg negative were observed for
      additional 2 years. Results of these studies have been previously reported. In
      this study, these children were followed for 2 additional years. Data gathered
      from medical record review included weight, height, signs and symptoms of
      hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B
      virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological
      treatments for CHB were allowed according to the practices of individual
      investigators and were documented. Subjects were divided into two groups for
      analysis, those who had achieved virological response (VR), defined as HBeAg
      negative and undetectable HBV DNA by the bDNA assay by the end of the extension
      study at 3 years, and those who had not. In those who had achieved VR by the end
      of the extension study, long-term durability of HBeAg seroconversion was 82% and
      >90% in those who had received lamivudine for 52 weeks and at least 2 years
      respectively. This compares to 75% for those who had achieved seroconversion
      after placebo. In those who had not achieved VR by the end of the extension
      study, an additional 11% did so by the end of the study; they had all received
      lamivudine in the previous trial, and none had received further treatment during
      the study. Eight children lost hepatitis B surface antigen during the study and
      all had received lamivudine at some point during the previous trials. Evaluation
      of safety data revealed no SAEs related to lamivudine. There was no effect of
      treatment on weight or height z scores. Clinically benign ALT flares (>10 times
      normal) were seen in 2% of children. Favourable outcomes from lamivudine
      treatment of CHB in children are maintained for at least several years after
      completion of treatment. Up to 3 years of lamivudine treatment is safe in
      children.

PMID- 18088242
TI  - Incidence of hepatocellular carcinoma among individuals with hepatitis B virus
      infection identified using an automated data algorithm.
AB  - The purpose of this study was to develop an algorithm for identifying patients
      with chronic hepatitis B virus (HBV) using automated data sources from two US
      health systems and evaluate the algorithm's performance by quantifying the
      incidence of hepatocellular carcinoma (HCC) among chronic HBV patients. To allow
      comparisons with estimates from automated databases that may not contain all data
      elements used in this algorithm, we created three definitions of chronic HBV
      infection and used these definitions to create three overlapping cohorts. We
      compared the incidence of HCC in each cohort with the incidence of HCC in a
      matched general population comparison cohort with no evidence of HBV. Patients
      who met the most stringent criteria for chronic HBV infection (based on the
      standard definition of 6 months of infection using repeat laboratory tests and
      record review) were 146 times more likely to develop HCC than matched comparison
      patients (adjusted hazard ratio = 146.5, 95% CI: 74.0-289.8). Those not meeting
      the stringent criteria, but who met the criterion of at least one positive
      hepatitis B surface antigen test were 30 times more likely to develop HCC than
      comparison patients (adjusted hazard ratio = 29.8, 95% CI: 16.5-53.6). Finally,
      patients who met the criterion based on at least one HBV diagnosis were 38 times
      more likely to develop HCC than matched comparison patients (adjusted hazard
      ratio = 37.8, 95% CI: 25.9-55.1). The magnitude of the relative increase in HCC
      risk seen using different criteria used to define HBV infection indicate that
      these automated data algorithms can identify patients with chronic HBV infection.

PMID- 18088243
TI  - Exacerbation of chronic hepatitis B infection after delivery.
AB  - During pregnancy several alterations in the immune status allow mothers to
      tolerate the genetically different foetal tissues. We investigated the evolution
      of liver disease during and after pregnancy in chronic hepatitis B patients.
      Between 1998 and 2006 there were 38 pregnancies in 31 chronic hepatitis B 's'
      antigen-positive women at our liver unit. Twenty-four subjects (63%) were
      hepatitis B 'e' antigen (HBeAg)-positive, 14 (37%) HBeAg-negative. In 13
      pregnancies (34%), lamivudine therapy was started during the last trimester of
      pregnancy to lower hepatitis B virus (HBV) DNA levels to reduce the risk of
      vertical transmission. A significant increase in liver disease activity after
      pregnancy, defined as a three times increase in alanine aminotransferase (ALT)
      within 6 months after delivery, occurred in 17 of 38 patients (45%). In those
      treated with lamivudine during the last trimester of pregnancy, this occurred in
      even 8/13 patients (62%). Prediction during pregnancy of these exacerbations was
      not possible using HBV DNA, ALT level, HBeAg status or any other characteristic.
      The median maximal ALT of these exacerbations was 4.0 x ULN and none led to
      decompensated liver disease. In conclusion, a significant increase in liver
      inflammation occurs often after pregnancy. This may be due to a reactivation of
      the immune system after delivery. Based on our data we recommend monitoring
      closely and if necessary treating women with chronic HBV shortly after delivery.

PMID- 18088244
TI  - Symptomatology and health attitudes of chronic hepatitis B patients in the USA.
AB  - This study was conducted to understand the symptomatology, attitudes, and
      behaviours of chronic hepatitis B (CHB) patients in the USA. CHB patients
      enrolled in this study were recruited through multiple methods, including
      newspaper advertisements. Interviews were conducted in multiple languages, and
      all participants had a history of CHB infection for at least 6 months. Patients
      with documented human immunodeficiency virus or hepatitis C virus coinfection
      were excluded from data analyses, resulting in a total study population of 258
      respondents who completed interviews between April and June 2004. The majority of
      monoinfected patients were male (57%) and non-Asian (92%, including 52%
      Caucasian, 32% African American and others). Length of diagnosis was 5.8 years
      for all participants (9.1-year Asian and 5.1-year non-Asian). Ninety-five per
      cent of CHB patients reported symptoms of differing severity in the 12 months
      prior to the survey. The most common symptoms included fatigue/loss of energy
      (90%) and loss of appetite (79%). Non-Asian patients described greater
      symptomatology, and were more likely than Asians to consider CHB an overriding
      concern in their daily activities. Patients were treated either currently or
      previously with interferon (IFN) described greater symptomatology than those
      treated without IFN. Survey results indicate that CHB patients may have greater
      symptomatology than recognized. Disease perceptions and treatment attitudes
      differ between Asian and non-Asian ethnic groups, with the former appearing to be
      more accepting and less concerned about the disease. Additional research about
      CHB symptomatology and health attitudes by ethnicity is needed to ensure that
      individuals with CHB are educated on the potential health risks and the
      availability of current treatment options.

PMID- 18088246
TI  - Association of amino acid variations in the NS5A and E2-PePHD region of hepatitis
      C virus 1b with hepatocellular carcinoma.
AB  - NS5A and E2 proteins of the hepatitis C virus (HCV) have the potential to repress
      protein kinase R (PKR) that exerts a tumour suppressor function. We investigated
      the relationship between amino acid variations in the NS5A-PKR-binding domain and
      E2-PKR-eIF2alpha phosphorylation homology domain (PePHD) region and the
      development of hepatocellular carcinoma (HCC) in chronic HCV-1b patients. In a
      cross-sectional, hospital-based setting, we compared the amino acid sequences of
      NS5A-PKR-binding domain and E2-PePHD in the sera of 104 chronic hepatitis, 44
      cirrhosis and 96 HCC patients. The nucleotide sequences were inferred by direct
      sequencing of the amplified HCV products and deduced amino acid were compared
      with the sequence of HCV-J. By univariate analysis, old age, lower viral load,
      fewer amino acid substitutions in the NS5A-PKR-binding domain (codons 2209-2274)
      and the interferon sensitivity-determining region (ISDR; codons 2209-2248), and
      wild-type amino acid at codon 2209 and codon 2240 was significantly correlated
      with HCC, whereas substitutions in the E2-PePHD was not. Patients with a mutated
      type (> or = 4) NS5A-ISDR had a lower prevalence of HCC than those with
      intermediate or wild type (P < 0.05). Based on stepwise logistic regression
      analysis, age [odds ratio (OR): 1.132, P < 0.001], viral load (OR: 0.305, P <
      0.001) and mutated-type ISDR (OR: 0.137, P = 0.001) were independently associated
      with HCC. In conclusion, NS5A-ISDR variations may play an important role in the
      development of HCV-related HCC.

PMID- 18088247
TI  - Assessment of hepatitis C virus-RNA clearance under combination therapy for
      hepatitis C virus genotype 1: performance of the transcription-mediated
      amplification assay.
AB  - Monitoring of HCV-RNA in blood during antiviral therapy is performed mostly by
      commercially available reverse transcription polymerase chain reaction-based (RT
      PCR) assays, with a lower detection limit of 30-50 IU/mL of HCV-RNA. Use of
      different tests in the pivotal trials of combination therapy has generated some
      discordance, in terms of predictive value of the early virological response
      (EVR). To evaluate whether the use of a more sensitive test, as a qualitative
      assay based on transcription mediated amplification (TMA) with a lower detection
      limit of 5-10 IU/mL of HCV-RNA, may obtain a better prediction of EVR and of the
      ultimate virological outcome, we retrospectively evaluated serial samples from
      108 naive patients with HCV genotype 1 chronic hepatitis, treated with pegylated
      alpha2b interferon plus ribavirin for 48 weeks and with a 24 weeks stopping rule.
      Serum samples of patients, obtained during treatment at weeks 4, 12, 24 and 48
      and after treatment at week 24, were evaluated by TMA. Comparison of the RT-PCR
      and TMA assays for the qualitative detection of HCV-RNA showed no significant
      differences in performance when these tests were used at the end of the treatment
      period for assessing patients without an on-treatment virological response and
      those who eventually obtain a sustained virological response. Our results show
      instead that the use of TMA assay to detect HCV-RNA at 12 and 24 weeks of the
      combination therapy is more effective than RT-PCR in identifying patients with
      the highest probability of sustained HCV-RNA clearance.

PMID- 18088245
TI  - Exploring differences in response to treatment with peginterferon alpha 2a (40kD)
      and ribavirin in chronic hepatitis C between genotypes 2 and 3.
AB  - Chronic hepatitis C virus (HCV) infections with genotype 2 or 3 are associated
      with favourable sustained virologic response (SVR) rates. However, genotype 3 may
      respond less well. We reassessed all treatment-naive patients with genotype 2 and
      3 participating in a large expanded-access, non-randomized, open-label trial,
      evaluating 180microg pegylated interferon (peg-IFN) alpha-2a (40kD) once weekly
      and 800 mg/day ribavirin for 24-48 weeks. Factors measured prior to initiation of
      antiviral therapy were considered in the multiple logistic regression model for
      predicting SVR. In total, 180 patients were analysed of which 72 (40%) were
      infected by genotype 2 and 108 (60%) genotype 3. The baseline characteristics
      between patients infected by genotype 2 or 3 were no different including the
      distribution of hepatic fibrosis stages by METAVIR score. Overall SVR was lower
      in those patients infected with genotype 3. The significant multivariate
      predictors of lack of SVR were hepatic fibrosis (P = 0.014) and genotype 3 (P =
      0.030). The negative impact of cirrhosis (METAVIR score F4) on treatment response
      was more evident among subjects with genotype 3 than those with genotype 2 (P =
      0.027). There is significant interaction between cirrhosis and genotype 3 leading
      to a poor antiviral response in such patients requiring an alternate management
      strategy. This finding should be confirmed in a larger population.

PMID- 18088248
TI  - Association of TLR7 single nucleotide polymorphisms with chronic HCV-infection
      and response to interferon-a-based therapy.
AB  - An efficient immune response against hepatitis C virus (HCV) is necessary to
      clear infection. As HCV is a single-stranded RNA virus, a role for TLR7 in the
      immune response against HCV is possible, and early clinical studies have
      demonstrated an antiviral effect of TLR7 stimulation. We tested the hypothesis
      that genetic variations of TLR7 are associated with chronic HCV-infection and
      outcome of therapy. The prevalence of three TLR7 variations was analysed in 978
      patients with chronic HCV-infection, 898 patients with chronic liver disease of
      other aetiologies, and in 203 healthy controls. The prevalence of TLR7 variations
      was correlated with the response to interferon-alpha-based treatment in 544
      patients with chronic HCV-infection. We analysed TLR7 polymorphisms by melting
      curve analysis and reconstructed haplotypes. The c.32A>T variation was over
      represented in female patients with chronic HCV-infection compared to patients
      with other chronic liver diseases and to healthy controls (P < 0.05). In
      contrast, c.2403 G>A was less prevalent in male patients with chronic HCV
      infection (P < 0.05). No association was observed for the third variant, c.1
      120T>G. Haplotype analysis confirmed the differential distribution of TLR7
      variants between the groups. Within the group of female patients with chronic HCV
      infection, c.32T was predictive of an unfavourable outcome of interferon-alpha
      therapy (P < 0.05). This study reports the association of TLR7 variants with
      chronic HCV-infection and with the response to interferon-alpha therapy in
      patients with chronic HCV-infection. Our results suggest that variations of TLR7
      impair the immune response to HCV and imply a gender-specific effect of this X
      chromosomal variation.

PMID- 18088249
TI  - Antibodies to tissue transglutaminase: an immune link between the gut, the
      coronaries and the myocardium?

PMID- 18088250
TI  - What will whole genome searches for susceptibility genes for common complex
      disease offer to clinical practice?
AB  - In the developed world the majority of disease results from common, but complex
      disorders such as diabetes, obesity and cancer. Genetic variation explains a
      large proportion of an individual's risk of developing these diseases; however,
      success in identifying the particular gene variants involved has been limited.
      Recent advances in high-throughput genotyping technology, and a better
      understanding of the genetic architecture of complex disease has led to the
      development of genome-wide association studies (GWA), which are providing novel
      and important insights into disease processes. The results from these studies
      could be of substantial clinical importance in the relatively near future. In
      this review, we present some recent, exciting findings from studies that have
      used the GWA approach, and discuss the clinical application of identifying
      disease susceptibility genes and variants.

PMID- 18088251
TI  - Antitissue transglutaminase antibodies in acute coronary syndrome: an alert
      signal of myocardial tissue lesion?
AB  - BACKGROUND AND AIM: Antitransglutaminase, previously considered identical to
      antiendomysial in coeliac sprue (CS), have been reported in end-stage heart
      failure. To clarify the above-mentioned data, we evaluated these antibodies in a
      cohort of cardiological patients with respect to troponin I, creatine kinase
      (CK), MB fraction creatine kinase (CK-MB mass) and myoglobin. METHODS: Forty-one
      patients with acute coronary syndrome (ACS), 39 with dilated cardiomyopathy
      (DCM), 45 with CS and 58 blood donors (BDs) were evaluated. Antitransglutaminase
      and antiendomysial antibodies were tested in serum of the patients being studied.
      RESULTS: High-positive antitransglutaminase values were found in CS, whilst low
      positive values were also found in ACS and DCM. In patients at the second ACS,
      antibody levels were higher than in those at the first cardiac event. In patients
      with infarct Q, antitransglutaminase were higher than those in infarct non-Q, in
      which antibody levels were higher than those in unstable angina. A correlation
      between antitransglutaminase and troponin I, CK, CK-MB mass and myoglobin was
      found. Finally, antibody levels rose to reach a peak at 30 days from the cardiac
      event, whereas after further 150 days, approached the values of BDs.
      Antiendomysial were detectable only in CS. CONCLUSIONS: Data highlight that
      antitransglutaminase can occur in cardiological patients, and that these
      antibodies are related to the severity/extent of the myocardial tissue lesion.
      This feature suggests a loss of specificity for antitransglutaminase in CS.
      Furthermore, the possibility of employing these antibodies in the long-term
      follow-up of ACS, could become an object of interesting discussion.

PMID- 18088252
TI  - Efficacy and safety of anticoagulant prophylaxis to prevent venous
      thromboembolism in acutely ill medical inpatients: a meta-analysis.
AB  - OBJECTIVES: Venous thromboembolism (VTE) is a potentially serious complication of
      hospitalization and immobilization. The use of anticoagulant prophylaxis in
      acutely ill medical inpatients is still under debate. New data including a recent
      meta-analysis have recently been published. We aim at studying the efficacy and
      safety of anticoagulant prophylaxis in acutely ill medical inpatients, and
      demonstrate differences between meta-analyses due to different data extraction
      from the heterogeneous studies included. SUBJECTS: The Cochrane Library, MEDLINE
      and EMBASE were searched from 1980 to present. Manual searches were performed
      regarding abstracts from major meetings. Seven blinded randomized controlled
      clinical trials assessing the prophylactic effect of heparin in acutely ill
      medical patients were identified and included in the meta-analysis. RESULTS: Low
      molecular weight heparin (LMWH) prophylaxis prevented 48% of symptomatic
      pulmonary embolism (PE), 48% of symptomatic deep vein thrombosis (DVT) (not
      significant) and 51% of asymptomatic DVT. A nonsignificant trend towards higher
      bleeding risk during LMWH prophylaxis was found. Death was not significantly
      affected. We compared our data with a recent meta-analysis with different study
      selection and data extraction and found similar results. CONCLUSIONS: As DVT and
      PE are manifestations of the same illness, VTE, one can argue that anticoagulant
      prophylaxis prevents approximately half of the expected events. Most medical
      inpatients have short hospital stays, and a low risk of VTE. The important task
      for the clinician is to identify patients with a sufficiently high risk of
      symptomatic VTE to warrant LMWH prophylaxis. Despite differences in study
      selection and data extraction, our study shows results similar to a recent meta
      analysis.

PMID- 18088253
TI  - Two SNPs in the promoter region of the CTLA-4 gene affect binding of
      transcription factors and are associated with human myasthenia gravis.
AB  - OBJECTIVES: The molecular mechanisms underlying the regulation of the CD152 (CTLA
      4) gene are largely unknown. Two single nucleotide polymorphisms (SNPs) located
      in the promoter region are suspected to contribute to the pathogenesis of
      myasthenia gravis (MG) through regulation of gene expression. SETTING, SUBJECTS
      AND DESIGN: One hundred and sixty-five unrelated Swedish-Caucasian patients with
      MG (103 females and 62 males, age 17 to 92 years) and 148 ethnically matched
      healthy individuals were studied. Gene typing of two SNPs (T/C(-1772) and A/G(
      1661)) and quantification of soluble CD152 were performed in the patients.
      Besides the association studies, the function of these two SNPs is characterized.
      RESULTS: We present new genetic associations of two SNPs in the CD152 gene with
      human MG. These SNPs located in the promoter region are involved in
      transcriptional binding activity for Nuclear Factor I (NF-1) and c/EBPbeta, as
      demonstrated using chromatin immunoprecipitation and electromobility shift assay.
      MG patients with the T/C(-1772) polymorphism have elevated levels of sCD152 in
      sera. CONCLUSIONS: The two SNPs in the promoter region are associated with MG and
      might cause abnormal alternative splicing and affect the expression of CD152,
      thereby contributing to the pathogenesis of MG.

PMID- 18088254
TI  - T64A polymorphism in beta3-adrenergic receptor gene (ADRB3) and coronary heart
      disease: a case-cohort study and meta-analysis.
AB  - OBJECTIVES: A missense mutation of the human ADRB3 gene replacing tryptophan with
      arginine at codon 64 (Trp64Arg) has been related to obesity, insulin resistance,
      earlier onset of noninsulin-dependent diabetes mellitus and hypertension. These
      findings may also suggest an increased risk of coronary heart disease (CHD). We
      therefore investigated the role of this polymorphism on the occurrence of acute
      myocardial infarction (AMI) and CHD in a population of healthy Dutch women.
      DESIGN: We performed a case-cohort study in a prospective cohort of 15,236
      initially healthy Dutch women. We applied a Cox proportional hazards model with
      an estimation procedure adapted for case-cohort designs to study the relationship
      between the polymorphism and AMI (n = 71) and CHD (n = 211). In addition, a meta
      analysis of published studies was performed using a random effect model. RESULTS:
      Using the dominant model, carriers of the arginine allele (n = 222) compared to
      those with the more common genotype (n = 1508) were not at increased risk of AMI
      (hazard ratio = 1.60; 95% CI, 0.86-2.96) and for CHD (HR = 1.36; 95% CI, 0.92
      2.02). We did not find any relationship using recessive and additive models,
      either. Our meta-analysis corroborated these findings by showing no significant
      association between the polymorphism and risk of CHD using different genetic
      models. CONCLUSIONS: Our study in combination with a meta-analysis of previous
      reports do not provide support for a role of missense mutation replacing
      tryptophan with arginine at codon 64 (Trp64Arg) at the human ADRB3 gene in CHD
      risk.

PMID- 18088255
TI  - Estrogen induced hypertriglyceridemia in an apolipoprotein AV deficient patient.

PMID- 18088257
TI  - Editorial: Clinical nursing knowledge and interventions.

PMID- 18088258
TI  - A systematic review of empirical studies between 1966 and 2005 of patient
      outcomes of total hip arthroplasty and related factors.
AB  - AIM: To determine patient outcomes of total hip arthroplasty and the research
      methods used to produce knowledge of use to clinical nursing and for purposes of
      health education. The review consists of three parts. Firstly, it describes the
      patient outcomes of total hip arthroplasty. Secondly, it addresses the factors
      related to the patient outcomes and thirdly the research methods used are
      explored. BACKGROUND: Previous research has identified that total hip
      arthroplasty is a very common procedure to reduce pain and improve physical
      function in patients with osteoarthritis. The greatest improvements have been
      found in reduction in pain. METHODS: Two databases, Medline and CINAHL were
      searched from 1966-2005. Studies were eligible for review and included if they
      met the following criteria: (1) publication in English, (2) empirical research
      and (3) the indication for total hip arthroplasty was osteoarthritis; 17 studies
      met the criteria. RESULTS: Total hip arthroplasty resulted in pain relief,
      improved physical function and enhanced health-related quality of life regardless
      of patients' characteristics, type of operation or type of prosthesis. The only
      factor affecting patient outcomes was patients' poor pre-operative function.
      These patients were more likely to have postoperative pain and low postoperative
      physical function. Long-waiting time for surgery may reduce quality-adjusted life
      years. Different kinds of questionnaires were used in the studies reviewed
      leaving out patients' perceptions concerning the outcomes of total hip
      arthroplasty. CONCLUSIONS: Patients' perceptions should be assessed more closely
      in further research to gain subjective knowledge about the outcomes of total hip
      arthroplasty. This could be achieved by using qualitative methods also. RELEVANCE
      TO CLINICAL PRACTICE: The findings can be seen as a challenge for nurses to plan
      patients' education. It is also important that the outcomes of total hip
      arthroplasty correspond to patients' expectations. Patients' preoperative
      function should be taken into consideration when planning the timing of surgery
      so that the best possible outcomes were attainable.

PMID- 18088259
TI  - Epidemiology and prevention of head injuries: literature review.
AB  - AIM AND OBJECTIVES: To identify evidence-based reports on the epidemiology of
      head injuries to develop guidelines for primary prevention activities by public
      health nurses. BACKGROUND: Head injury is a major cause of morbidity, mortality,
      disability and lost years of productive life in the population under 40-45 years
      of age. Prevention strategies such as legislation on car seat belts, drink
      driving and health and safety at work have led to reductions in its incidence. As
      well as the personal repercussions for those injured and their families, there
      are resource implications for healthcare provision. There is a potential role for
      public health nurses in reducing this burden. METHODS: A search of MEDLINE,
      PubMed, Science Direct, BNI and CINAHL was carried out for the period 1990-2005
      using the keywords: head injury, brain injury, traumatic brain injury, head
      trauma, incidence, prevalence, epidemiology and prevention of head injuries.
      RESULTS: Comparison of the data is difficult because of the use of different
      definitions of injury, criteria for severity, geographical bases and timeframes.
      Those at greatest risk seem to be young men and older people. The former are more
      implicated in traffic and work accidents and in physical violence, while older
      people are more susceptible to traffic accidents as pedestrians and to falls. The
      incidence in lower socio-economic groups is greater. CONCLUSIONS: The evidence
      base for the primary prevention of head injury is weak. Standardized definitions
      and classification systems need to be used in future epidemiological studies to
      permit comparisons across studies. RELEVANCE TO CLINICAL PRACTICE: There is a
      role for public health nurses in developing primary prevention campaigns in
      schools and local communities. Key target groups are young men and older people
      and campaigns need to tackle the particular issues relevant to these groups.

PMID- 18088260
TI  - The effects of gender and age on health-related quality of life following kidney
      transplantation.
AB  - AIMS AND OBJECTIVES: To evaluate whether gender, age and their interaction affect
      health-related quality of life and overall health status following kidney
      transplantation. BACKGROUND: Some investigators have examined the main effects of
      gender and/or age on health-related quality of life following kidney
      transplantation, but the potential interaction effect of these measures on this
      outcome has not been reported. DESIGN: This was a cross-sectional, single-centre
      study, based in one US geographic area. METHODS: Self-report survey data were
      provided by adult kidney transplant recipients using the SF-36 Health Survey (SF
      36) and a visual analogue scale of overall health. SF-36 physical and mental
      component summary and individual scales and overall health were measured
      prospectively at one time point post-transplant. All adult patients were eligible
      to participate and rolling enrolment was employed. Statistical effects were
      tested using analysis of covariance (controlling for time post-transplant).
      RESULTS: Subjects (n = 138) included 66 women and 72 men. There were no effects
      of gender, age group, or their interaction on MCS or overall health scores (all p
      >or= 0.12). Physical component summary scale data demonstrated: (i) a significant
      effect of gender (p = 0.025); (ii) a statistically marginal effect of age group
      (p = 0.068); and (iii) a statistically marginal gender by age group interaction
      effect (p = 0.066). Women reported poorer scores on the SF-36 physical
      functioning (p = 0.049), role physical (p = 0.014) and bodily pain scales (p =
      0.028). There was an effect of age group on physical functioning (p = 0.005),
      with younger patients reporting higher scores. CONCLUSIONS: Women report lower
      scores on several physical measures and may experience a greater reduction with
      age in physical health-related quality of life than men. Physical functioning
      declines with age following kidney transplantation. RELEVANCE TO CLINICAL
      PRACTICE: Findings may help healthcare professionals to develop gender- and age
      specific interventions to optimize health-related quality of life of kidney
      transplant patients.

PMID- 18088261
TI  - Levels of fatigue in people with ESRD living in far North Queensland.
AB  - AIM: Levels of fatigue as experienced by people with end stage renal disease
      (ESRD), were assessed using the Fatigue Severity Scale (FSS). BACKGROUND:
      Fatigue, a common symptom reported by people with ESRD, is a multifaceted,
      subjective experience, which is readily understood by individuals but difficult
      to measure. There is limited understanding of the level of fatigue experienced by
      people with ESRD, with research currently limited to people treated with
      haemodialysis. METHOD: The FSS was completed by 92 people with ESRD who were
      patients of a renal service in far North Queensland, Australia. Demographic and
      renal health history data were also collected with the self-report survey.
      RESULTS: Comparisons were preformed between overall fatigue levels and different
      renal disorders, genders, ethnicity and renal replacement therapy (RRT).
      Participants in this study were more fatigued than the general population; there
      was no difference in levels of fatigue between gender and ethnicity. Participants
      with diabetic nephropathy and those who were predialysis were the most fatigued.
      A significant difference between mean fatigue scores was found for type of RRT
      [F(3,88) = 2.4, p < 0.05], with participants using peritoneal dialysis reporting
      the most fatigue. Additionally, participants categorized according to type of
      RRT, erythropoietin replacement therapy and current haemoglobin levels revealed
      significant mean differences on fatigue levels [F(3,88) = 2.74, p < 0.05].
      RELEVANCE TO CLINICAL PRACTICE: People with ESRD experience considerable fatigue;
      it is particularly important for nurses to understand this level of fatigue
      impacts on the daily life of patients. These findings provide the preliminary
      evidence to support the development of renal nursing practice guidelines related
      to symptom recognition and management of fatigue.

PMID- 18088262
TI  - Service needs of residents in community-based long-term care facilities in
      northern Taiwan.
AB  - AIM: The purpose of this study was to quantify the service needs of residents in
      community-based long-term care (LTC) facilities and to determine their
      predictors. BACKGROUND: Disabled older family members in Taiwan are often
      eventually sent to community-based LTC facilities. Many service needs of these
      residents are likely to go unmet. METHODS: A cross-sectional survey was used.
      This involved purposive sampling of 132 residents from 10 LTC facilities in
      Taipei City. A previously developed LTC service need assessment scale was used to
      collect information about the residents' needs in terms of five kinds of LTC
      services, namely health education, skilled nursing services, referral services,
      activities of daily living (ADL) assistance and instrumental activities of daily
      living assistance. RESULTS: The mean age of residents was 75.2 years. The average
      period of institutionalization was 21.93 months. Overall, 70% of the residents
      had either complete or partial ADL function dependency. Among the specific ADL
      function dependencies of the residents, inability to take a bath was the most
      common. The most significant predictors of service needs were health status, age,
      number of children, number of medical diagnoses and whether the stay is self
      choice. These combined variables explained between 25.5% and 41.6% of the
      variance of the need for LTC services. CONCLUSION: The findings of this study
      show that age, health status, number of children, number of medical diagnoses and
      whether the stay is self-choice are significant determinants of residents' needs
      in terms of LTC. Assessment of the extent to which facilities meet the residents'
      needs is the first step in providing the most cost-effective allocation of scarce
      resources. RELEVANCE TO CLINICAL PRACTICE: It is suggested that, if reimbursement
      by the National Health Insurance system of physician visits, including
      psychiatric visits, to LTC facilities were allowed, this would improve quality of
      care.

PMID- 18088263
TI  - A randomized controlled trial of a community nurse-supported hospital discharge
      programme in older patients with chronic heart failure.
AB  - AIMS AND OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of a
      community nurse-supported hospital discharge programme in preventing hospital re
      admissions, improving functional status and handicap of older patients with
      chronic heart failure. DESIGN: Randomized controlled trial; 105 hospitalized
      patients aged 60 years or over with chronic heart failure and history of hospital
      admission(s) in previous year were randomly assigned into intervention group (n =
      49) and control group (n = 56) for six months. Intervention group subjects
      received community nurse visits before discharge, within seven days of discharge,
      weekly for four weeks, then monthly. Community nurse liaised closely with a
      designated specialist in hospital and were accessible to subjects during normal
      working hours. Control and intervention group subjects were followed up in the
      same specialist medical clinics. Primary outcome was the rate of unplanned re
      admission at six months. Secondary outcomes were number of unplanned re
      admissions, six-minute walking distance, London Handicap Scale and public health
      care and personal care costs. RESULTS: At sixth months, the re-admission rates
      were not significantly different (46 vs. 57% in control subjects, p = 0.233, Chi
      square test). But the median number of re-admissions tended to lower in the
      intervention group (0 vs. 1 in control group, p = 0.057, Mann Whitney test).
      Intervention group subjects had less handicap in independence (median change 0
      vs. 0.5 in control subjects, p = 0.002, Mann Whitney test), but there was no
      difference in six-minute walking distance. There was no significant group
      difference in median total public health care and personal care costs.
      CONCLUSION: Community nurse-supported post-discharge programme was effective in
      preserving independence and was probably effective in reducing the number of
      unplanned re-admissions. The cost benefits to public health care were not
      significant. RELEVANCE TO CLINICAL PRACTICE: Older chronic heart failure patients
      are likely to benefit from post-discharge community nurse intervention
      programmes. More comprehensive health economic evaluation needs to be undertaken.

PMID- 18088264
TI  - Falls and fall risk among nursing home residents.
AB  - AIM AND OBJECTIVES: The aim of this study was to identify risk factors for falls
      in older people living in nursing homes. BACKGROUND: Impaired cognitive function
      and a poor sense of orientation could lead to an increase in falls among those
      with impaired freedom of movement. Many accidents occur while an older person is
      walking or being moved. METHOD: The study was carried out over four years (2000
      2003) and 21 nursing home units in five municipal homes for older people in
      Stockholm, Sweden, participated. A questionnaire was sent to staff nurses,
      including questions on fall risk assessments, falls, fractures, medication and
      freedom-restricting measures, such as wheelchairs with belts and bed rails. The
      data were aggregated and not patient-bound. The study covered 2,343 reported
      incidents. RESULTS: There was a significant correlation between falls and
      fractures (r = 0.365, p = 0.004), fall risk and use of wheelchairs (r = 0.406, p
      = 0.001, safety belts (r = 0.403, p = 0.001 and bed rails (r = 0.446, p = 0.000)
      and between the occurrence of fractures and the use of sleeping pills with
      benzodiazepines (r = 0.352, p = 0.005). Associations were also found between fall
      risk and the use of anti-depressants (r = 0.412, p = 0.001). CONCLUSION: In
      clinical practice, patient safety is very important. Preventative measures should
      focus on risk factors associated with individuals, including their environment.
      Wheelchairs with safety belts and bed rails did not eliminate falls but our
      results support the hypothesis that they might be protective when used
      selectively with less anti-depressants and sleeping pills, especially
      benzodiazepines.

PMID- 18088267
TI  - Estimating the cost of epilepsy in Europe: a review with economic modeling.
AB  - PURPOSE: Based on available epidemiologic, health economic, and international
      population statistics literature, the cost of epilepsy in Europe was estimated.
      METHODS: Europe was defined as the 25 European Union member countries, Iceland,
      Norway, and Switzerland. Guidelines for epidemiological studies on epilepsy were
      used for a case definition. A bottom-up prevalence-based cost-of-illness
      approach, the societal perspective for including the cost items, and the human
      capital approach as valuation principle for indirect costs were used. The cost
      estimates were based on selected studies with common methodology and valuation
      principles. RESULTS: The estimated prevalence of epilepsy in Europe in 2004 was
      4.3-7.8 per 1,000. The estimated total cost of the disease in Europe was euro15.5
      billion in 2004, indirect cost being the single most dominant cost category
      (euro8.6 billion). Direct health care costs were euro2.8 billion, outpatient care
      comprising the largest part (euro1.3 billion). Direct nonmedical cost was euro4.2
      billion. That of antiepileptic drugs was euro400 million. The total cost per case
      was euro2,000-11,500 and the estimated cost per European inhabitant was euro33.
      CONCLUSIONS: Epilepsy is a relevant socioeconomic burden at individual, family,
      health services, and societal level in Europe. The greater proportion of such
      burden is outside the formal health care sector, antiepileptic drugs representing
      a smaller proportion. Lack of economic data from several European countries and
      other methodological limitations make this report an initial estimate of the cost
      of epilepsy in Europe. Prospective incidence cost-of-illness studies from well
      defined populations and common methodology are encouraged.

PMID- 18088268
TI  - Drug resistance in epilepsy: more twists in the tale.

PMID- 18088269
TI  - Drug resistance in epilepsy: why is a simple explanation not enough?

PMID- 18088270
TI  - Where is the evidence that p-glycoprotein limits brain uptake of antiepileptic
      drug and contributes to drug resistance in epilepsy?

PMID- 18088271
TI  - Assessment of hairline EEG as a screening tool for nonconvulsive status
      epilepticus.

PMID- 18088275
TI  - Contrasting effects of basic fibroblast growth factor and epidermal growth factor
      on mouse neonatal olfactory mucosa cells.
AB  - Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) affect
      proliferation and survival of many cell types, but their role in the maintenance
      of olfactory mucosa cells remains unclear. In the neonatal mouse olfactory
      mucosa, cell proliferation mainly occurs in the neuroepithelium and, to a lesser
      extent, in the lamina propria. To establish whether bFGF and EGF affect
      proliferation and/or survival of these cells, we isolated olfactory mucosa cells
      from the neonatal mouse and cultured them as free-floating spheres under bFGF or
      EGF stimulation. Our data demonstrate that bFGF is a mitogen for the rapidly
      dividing cells (olfactory neuronal precursors and olfactory ensheathing cells),
      and also a survival factor for both slowly and rapidly dividing cells of the
      olfactory mucosa. In contrast, EGF appears to be primarily a survival factor for
      both the olfactory stem and precursor cells.

PMID- 18088276
TI  - Regulated recycling and plasma membrane recruitment of the high-affinity choline
      transporter.
AB  - The high-affinity choline transporter (CHT1) is responsible for uptake of choline
      from the synaptic cleft and supplying choline for acetylcholine synthesis. CHT1
      internalization by clathrin-coated vesicles is proposed to represent a mechanism
      by which high-affinity choline uptake can be modulated. We show here that
      internalized CHT1 is rapidly recycled back to the cell surface in both human
      embryonic kidney cells (HEK 293 cells) and SH-SY5Y neuroblastoma cells. This
      rapidly recycling pool of CHT1 comprises about 10% of total CHT1 protein. In the
      SH-SY5Y neuroblastoma cell line K(+)-depolarization promotes Ca(2+)-dependent
      increase in the rate of CHT1 recycling to the plasma membrane without affecting
      the rate of CHT1 internalization. K(+)-depolarization also increases the size of
      the pool of CHT1 protein that can be mobilized to the plasma membrane. Thus, the
      activity-dependent increase in plasma membrane CHT1 localization appears to be
      regulated by two mechanisms: (i) an increase in the rate of externalization of
      the intracellular CHT1 pool; and (ii) the recruitment of additional intracellular
      transporters to the recycling pool.

PMID- 18088277
TI  - Effect of minocycline on inflammation-induced damage to the blood-brain barrier
      and white matter during development.
AB  - Damage to white matter in some premature infants exposed to intrauterine
      infections is thought to involve disruption of the blood-brain barrier. We have
      examined the effect of minocycline, an agent reported to reduce brain damage
      resulting from inflammation, on inflammation-induced disruption of the blood
      brain barrier and damage to white matter. Post-natal marsupial opossums
      (Monodelphis domestica) were studied as most brain development in this species
      occurs after birth. Single intraperitoneal lipopolysaccharide (LPS) injection
      (0.2 mg/kg) with or without minocycline (45 mg/kg) at post-natal day (P)35 caused
      short-lasting barrier breakdown to plasma proteins but not to (14)C-sucrose. By
      P44, blood-brain barrier integrity was intact but a reduced volume of white
      matter was present. At P44 after prolonged inflammation (5 x 0.2 mg/kg LPS at 48
      h intervals), proteins from blood were observed within brain white matter and
      permeability to (14)C-sucrose in the hindbrain increased by 31%. The volume of
      the external capsule and the proportion of myelin were 70 and 57%, respectively,
      of those in control animals. Minocycline administered during prolonged
      inflammation restored blood-brain barrier integrity but not LPS-induced damage to
      white matter. These data suggest that long-term changes in blood-brain barrier
      permeability occur only after a prolonged period of inflammation during
      development; however, damage to white matter can result from even a short-lasting
      breakdown of the barrier. Manipulation of the inflammatory response may have
      implications for prevention of some developmentally induced neurological
      conditions.

PMID- 18088278
TI  - Involvement of AMPA receptor phosphorylation in antidepressant actions with
      special reference to tianeptine.
AB  - Depression is associated with abnormal neuronal plasticity. AMPA receptors
      mediate transmission and plasticity at excitatory synapses in a manner which is
      positively regulated by phosphorylation at Ser831-GluR1, a CaMKII/PKC site, and
      Ser845-GluR1, a PKA site. Treatment with the selective serotonin (5
      hydroxytryptamine; 5-HT) reuptake inhibitor fluoxetine increases P-Ser845-GluR1
      but not P-Ser831-GluR1. Here, it was found that treatment with another
      antidepressant, tianeptine, increased P-Ser831-GluR1 in the frontal cortex and
      the CA3 region of hippocampus and P-Ser845-GluR1 in the CA3 region of
      hippocampus. A receptorome profile detected no affinity for tianeptine at any
      monaminergic receptors or transporters, confirming an atypical profile for this
      compound. Behavioural analyses showed that mice bearing point mutations at both
      Ser831- and Ser845-GluR1, treated with saline, exhibited increased latency to
      enter the centre of an open field and increased immobility in the tail-suspension
      test compared to their wild-type counterparts. Chronic tianeptine treatment
      increased open-field locomotion and reduced immobility in wild-type mice but not
      in phosphomutant GluR1 mice. P-Ser133-CREB was reduced in the CA3 region of
      hippocampus in phosphomutant mice, and tianeptine decreased P-Ser133-CREB in this
      region in wild-type, but not in phosphomutant, mice. Tianeptine increased P
      Ser133-CREB in the CA1 region in wild-type mice but not in phosphomutant GluR1
      mice. There were higher basal P-Ser133-CREB and c-fos levels in frontal and
      cingulate cortex in phosphomutant GluR1 mice; these changes in level were
      counteracted by tianeptine in a GluR1-independent manner. Using phosphorylation
      assays and phosphomutant GluR1 mice, this study provides evidence that AMPA
      receptor phosphorylation mediates certain explorative and antidepressant-like
      actions under basal conditions and following tianeptine treatment.

PMID- 18088279
TI  - Isolating endogenous visuo-spatial attentional effects using the novel visual
      evoked spread spectrum analysis (VESPA) technique.
AB  - In natural visual environments, we use attention to select between relevant and
      irrelevant stimuli that are presented simultaneously. Our attention to objects in
      our visual field is largely controlled endogenously, but is also affected
      exogenously through the influence of novel stimuli and events. The study of
      endogenous and exogenous attention as separate mechanisms has been possible in
      behavioral and functional imaging studies, where multiple stimuli can be
      presented continuously and simultaneously. It has also been possible in
      electroencephalogram studies using the steady-state visual-evoked potential
      (SSVEP); however, it has not been possible in conventional event-related
      potential (ERP) studies, which are hampered by the need to present suddenly
      onsetting stimuli in isolation. This is unfortunate as the ERP technique allows
      for the analysis of human physiology with much greater temporal resolution than
      functional magnetic resonance imaging or the SSVEP. While ERP studies of
      endogenous attention have been widely reported, these experiments have a serious
      limitation in that the suddenly onsetting stimuli, used to elicit the ERP,
      inevitably have an exogenous, attention-grabbing effect. Recently we have shown
      that it is possible to derive separate event-related responses to concurrent,
      continuously presented stimuli using the VESPA (visual-evoked spread spectrum
      analysis) technique. In this study we employed an experimental paradigm based on
      this method, in which two pairs of diagonally opposite, non-contiguous disc
      segment stimuli were presented, one pair to be ignored and the other to be
      attended. VESPA responses derived for each pair showed a strong modulation at 90
      100 ms (during the visual P1 component), demonstrating the utility of the method
      for isolating endogenous visuo-spatial attention effects.

PMID- 18088280
TI  - Cholinergic modulation of visuospatial responding in central thalamus.
AB  - Central thalamus has extensive connections with basal ganglia and frontal cortex
      that are thought to play a critical role in sensory-guided goal-directed
      behavior. Central thalamic activity is influenced by cholinergic projections from
      mesopontine nuclei. To elucidate this function we trained rats to respond to
      lights in a reaction time (RT) task and compared effects of muscarinic (2.4, 7.3,
      22 nmol scopolamine) and nicotinic (5.4, 16, 49, 98 nmol mecamylamine)
      antagonists with the GABA(A) agonist muscimol (0.1, 0.3, 1.0 nmol) in central
      thalamus. We compared this with subcutaneous (systemic) effects of mecamylamine
      (3.2, 9.7, 29 micromol/kg) and scopolamine (0.03, 0.09, 0.26 micromol/kg).
      Subcutaneous scopolamine increased omissions (failure to respond within a 3-s
      response window) at the highest dose tested. Subcutaneous mecamylamine increased
      omissions at the highest dose tested while impairing RT and per cent correct at
      lower doses. Intrathalamic injections of muscimol and mecamylamine decreased per
      cent correct at doses that did not affect omissions or RT. Intrathalamic
      scopolamine increased omissions and RT at doses that had little effect on per
      cent correct. Anatomical controls indicated that the effects of mecamylamine were
      localized in central thalamus and those of scopolamine were not. Drug effects did
      not interact with attention-demanding manipulations of stimulus duration,
      proximity of stimulus and response locations, or stimulus array size. These
      results are consistent with the hypothesis that central thalamus mediates
      decisional processes linking sensory stimuli with actions, downstream from
      systems that detect sensory signals. They also provide evidence that this
      function is specifically influenced by nicotinic cholinergic receptors.

PMID- 18088281
TI  - Cognitive impairment and transmitter-specific pre- and postsynaptic changes in
      the rat cerebral cortex during ageing.
AB  - Recent studies suggest that age-related cognitive decline is correlated with an
      excitatory-inhibitory imbalance in synaptic discharges on pyramidal neurons. This
      study focuses on whether ageing and cognitive status correlates with relative
      numbers of excitatory and inhibitory presynaptic boutons. We investigated the
      density of excitatory and inhibitory presynaptic inputs across several areas of
      the rat cerebral cortex in young and aged male Fischer 344 rats. Aged animals
      were segregated into aged cognitively impaired (AI) and aged cognitively
      unimpaired (AU) groups using the Morris water maze. We applied
      immunohistochemistry to reveal the majority of excitatory and inhibitory
      presynaptic boutons captured with confocal microscopy and quantitative image
      analysis. A gradual decline in the density of excitatory and inhibitory
      presynaptic boutons occurred from young to AU to AI animals; however, the ratios
      of excitatory to inhibitory presynaptic bouton densities were not significantly
      altered. We further investigated the density of receptor scaffolding proteins
      representing key excitatory and inhibitory receptor postsynaptic sites, using
      antibodies against specific markers of excitatory and inhibitory postsynaptic
      densities, respectively. Significant changes in the ratios of excitatory to
      inhibitory postsynaptic densities were observed only in AI compared to young
      rats.

PMID- 18088282
TI  - Role of the amygdaloid cholecystokinin (CCK)/gastrin-2 receptors and terminal
      networks in the modulation of anxiety in the rat. Effects of CCK-4 and CCK-8S on
      anxiety-like behaviour and [3H]GABA release.
AB  - The amygdala plays a key role in fear and anxiety. The intercalated islands are
      clusters of glutamate-responsive GABAergic neurons rich in cholecystokinin (CCK)
      2 receptors which control the trafficking of nerve impulses from the cerebral
      cortex to the central nucleus of amygdala. In this study, the nature of the CCK
      glutamate-GABA interactions within the rat rostral amygdala, and their relevance
      for anxiety, were studied. CCK/gastrin-like immunoreactive nerve terminals were
      found to be mainly restricted to the paracapsular intercalated islands and the
      rostrolateral part of the main intercalated island. Behaviourally, the bilateral
      microinjection of CCK-4 (0.043-4.3 pmol/side) or CCK-8S (4.3 pmol/side) into the
      rostrolateral amygdala reduced the open-arm exploration in the elevated plus-maze
      without affecting locomotion. In contrast, neither CCK-4 nor CCK-8S (0.043-4.3
      pmol/side) had any effects in the shock-probe burying test as compared with their
      saline-treated controls. Biochemically, CCK-4 (0.3 and 1.5 microm), unlike CCK
      8S, enhanced significantly the K(+)-stimulated release of [(3)H]GABA from
      amygdala slices. These effects were fully prevented by prior superfusion of the
      slices with either the selective CCK-2 receptor antagonist CR2945 (3 microm), or
      6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX), 10 microm, a glutamatergic (+/-)
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor
      antagonist. It is suggested that CCK modulates glutamate-GABA mechanisms by
      acting on CCK-2 receptors via volume transmission occurring at the level of the
      basolateral amygdaloid nucleus and/or by synaptic or perisynaptic volume
      transmission in the region of the rostrolateral main and paracapsular
      intercalated islands, resulting in subsequent disinhibition of the central
      amygdaloid nucleus and anxiety or panic-like behaviour.

PMID- 18088284
TI  - Dopamine gene predicts the brain's response to dopaminergic drug.
AB  - Dopamine is critical for reward-based decision making, yet dopaminergic drugs can
      have opposite effects in different individuals. This apparent discrepancy can be
      accounted for by hypothesizing an 'inverted-U' relationship, whereby the effect
      of dopamine agents depends on baseline dopamine system functioning. Here, we used
      functional MRI to test the hypothesis that genetic variation in the expression of
      dopamine D2 receptors in the human brain predicts opposing dopaminergic drug
      effects during reversal learning. We scanned 22 subjects while they engaged in a
      feedback-based reversal learning task. Ten subjects had an allele on the Taq1A
      DRD2 gene, which is associated with reduced dopamine receptor concentration and
      decreased neural responses to rewards (A1+ subjects). Subjects were scanned
      twice, once on placebo and once on cabergoline, a D2 receptor agonist. Consistent
      with an inverted-U relationship between the DRD2 polymorphism and drug effects,
      cabergoline increased neural reward responses in the medial orbitofrontal cortex,
      cingulate cortex and striatum for A1+ subjects but decreased reward responses in
      these regions for A1- subjects. In contrast, cabergoline decreased task
      performance and fronto-striatal connectivity in A1+ subjects but had the opposite
      effect in A1- subjects. Further, the drug effect on functional connectivity
      predicted the drug effect on feedback-guided learning. Thus, individual
      variability in how dopaminergic drugs affect the brain reflects genetic
      disposition. These findings may help to explain the link between genetic
      disposition and risk for addictive disorders.

PMID- 18088285
TI  - Dopamine and cognitive control: the prospect of monetary gains influences the
      balance between flexibility and stability in a set-shifting paradigm.
AB  - Positive affect and the activity of the neurotransmitter dopamine seem to shift
      the balance between cognitive flexibility vs stability towards increased
      flexibility. Here we examined the impact of prospective monetary gains on this
      balance. Seventy healthy volunteers performed a set-shifting task comprising a
      condition in which a bias towards new stimuli helped to overcome perseveration
      and increased flexibility, and a second condition in which directing attention
      towards new stimuli increased distractibility. From previous studies of executive
      functions, two contrasting predictions can be derived: the prospect of monetary
      gains might either increase cognitive flexibility due to a dopamine release in
      the prefrontal cortex or increase stability due to an assessment of high utility
      of action processed in the anterior cingulated cortex and orbitofrontal cortex.
      Overall, we observed increased cognitive stability in the face of prospective
      gains (eta(2) = 7%). However, this effect was modulated by the subjective
      evaluation of the reward cues: participants who reported increasing their effort
      in response to reward cues showed increased cognitive stability, whereas those
      who reported a positive and relaxed attitude towards the reward cues showed
      increased flexibility (eta(2) = 11%). The results thus suggest that the
      flexibility-stability balance is modulated by the perceived effort needed to
      receive the potential reward. On a neuropsychological level, an interaction of
      dopaminergic and noradrenergic processes might be involved in the allocation of
      control.

PMID- 18088283
TI  - Training-induced changes in the expression of GABAA-associated genes in the
      amygdala after the acquisition and extinction of Pavlovian fear.
AB  - Previous work suggests the gamma-aminobutyric acid (GABA)ergic system may be
      dynamically regulated during emotional learning. In the current study we examined
      training-induced changes in the expression of GABA(A)-related genes and the
      binding of GABA receptor radioligands in the amygdala after the acquisition and
      extinction of Pavlovian fear. Using in situ hybridization, we examined the
      expression pattern changes of mRNAs for GABAergic markers in the lateral,
      basolateral and central subdivisions of the amygdala in C57Bl/6J mice. These
      markers included GABA-synthesizing enzymes (GAD67 and GAD65), major GABA(A)
      receptor subunits (alpha1, alpha2, alpha3, alpha5, beta2 and gamma2) and the
      expression of mRNAs that are involved in a variety of GABA-related intracellular
      processes, including GABA transporter-1 (GAT1), GABA(A) receptor-associated
      protein and the GABA(A) clustering protein, gephyrin. With fear conditioning, we
      found decreased mRNA levels of alpha1, alpha5 and GAD67, as well as deceased
      benzodiazepine binding in the amygdala. Fear extinction induced an increase in
      mRNA levels of alpha2, beta2, GAD67 and gephyrin, as well as a decrease in GAT1.
      Together, these findings indicate that the acquisition of fear induced a
      downregulation of mRNA markers related to a decrease in amygdala GABAergic
      function, whereas the acquisition of fear extinction produced an upregulation of
      GABAergic markers related to enhanced GABAergic transmission.

PMID- 18088287
TI  - Prospective evaluation of a protocol for reduced glucocorticoid replacement in
      transsphenoidal pituitary adenomectomy: prophylactic glucocorticoid replacement
      is seldom necessary.
AB  - BACKGROUND: Most pituitary surgery centres prescribe perioperative
      glucocorticoids to subjects undergoing transsphenoidal pituitary adenomectomy
      (TSA), despite reports suggesting this may be unnecessary. Evidence-based
      guidelines for glucocorticoid use in TSA have recently been published but there
      are no prospective studies of their utility. OBJECTIVE: To implement and assess a
      protocol for reduced glucocorticoid replacement for subjects undergoing TSA.
      DESIGN: Prospective and retrospective cohort study in an Australian pituitary
      surgery centre. PATIENTS AND MEASUREMENTS: Clinical and biochemical data for 56
      TSAs performed for non-ACTH-secreting tumours between March 2004 and April 2006
      were prospectively collected and compared with data for 47 TSAs performed between
      October 2001 and November 2003, before implementation of the protocol. In the
      prospective cohort, a postoperative days 1-3 morning serum cortisol threshold of
      250 nmol/l (91 microg/dl) was used to guide long-term glucocorticoid requirement.
      RESULTS: Implementation of the protocol was associated with significant
      reductions in dose and duration of glucocorticoid treatment post TSA in 44 'low
      risk' cases (no preoperative glucocorticoid use or evidence of pituitary
      apoplexy). In two low-risk cases, long-term glucocorticoid replacement was
      required despite postoperative cortisol greater than 250 nmol/l. Following the
      remaining 42 low-risk operations, glucocorticoid was not prescribed on hospital
      discharge on the basis of morning serum cortisol > 250 nmol/l and no clinical
      evidence of hypocortisolism. None of these 42 cases required glucocorticoid
      treatment for hypocortisolism following surgery. Short synacthen tests were
      performed in 35 of these subjects a minimum of 6 months after surgery and were
      normal. Use of the protocol was not associated with differences in postoperative
      complications. CONCLUSIONS: Reduced glucocorticoid replacement in TSA is safe and
      reduces patient exposure to glucocorticoids and their potential adverse events.
      The occurrence of hypocortisolism in two low-risk subjects with serum cortisol >
      250 nmol/l highlights the importance of daily clinical assessment when using this
      protocol.

PMID- 18088288
TI  - Measurement of basal growth hormone (GH) is a useful test of disease activity in
      treated acromegalic patients.
AB  - BACKGROUND: Nadir GH during oral glucose tolerance test (OGTT) is the gold
      standard test of GH secretion in treated acromegaly. However, it was recently
      reported that variability in GH is reduced postradiotherapy, making basal GH a
      potential surrogate marker for nadir GH in such patients. OBJECTIVE: We aimed to
      investigate how predictive basal GH is of nadir GH and IGF-I, and whether
      radiotherapy influenced these relationships. DESIGN: A total of 226 pairs of
      basal and nadir GH values from 76 treated acromegalic patients were analysed.
      Basal GH was defined as the fasting serum GH immediately prior to OGTT. RESULTS:
      A highly positive linear correlation (Pearson correlation = 0.955, P < 0.01)
      between basal and nadir GH was found. Negative predictive value for basal GH < 1
      microg/l with respect to nadir GH > 1 microg/l was 100% (53/53 in radiotherapy
      group, 15/15 in nonradiotherapy group). Positive predictive values for basal GH >
      2 microg/l with respect to nadir GH > 1 microg/l for patients treated and not
      treated with radiotherapy were 96.7% (88/91) and 95.2% (20/21), respectively. No
      significant difference between concordance of basal and nadir GH with IGF-I in
      assessment of disease activity was found. Discordance between IGF-I and nadir or
      basal GH < 1 microg/l was lower in the radiotherapy group than nonradiotherapy
      group, but this was nonsignificant. CONCLUSIONS: Basal GH < 1 microg/l and > 2
      microg/l are highly predictive of nadir GH < 1 microg/l and > 1 microg/l,
      respectively, regardless of previous radiotherapy. Basal GH is as good as nadir
      GH in concordance with IGF-I. We therefore suggest basal GH is a useful test of
      disease activity in treated acromegaly, and can reliably replace OGTT unless
      basal GH is between 1 microg/l and 2 microg/l.

PMID- 18088290
TI  - Maternity nursing: a delicate balance: how one hospital is getting it right.

PMID- 18088292
TI  - Adolescents and contraception: the nurse's role as counselor.

PMID- 18088293
TI  - Methadone and buprenorphine treatment during pregnancy: what are the effects on
      infants?

PMID- 18088294
TI  - Breastfeeding in the 21st century: overcoming barriers to help women and infants.

PMID- 18088295
TI  - Research in pregnant women: the challenges of informed consent.

PMID- 18088296
TI  - Reducing cardiovascular risk and managing dyslipidemia in women.

PMID- 18088297
TI  - Improving the process: increasing utilization, safety and satisfaction in a birth
      center.

PMID- 18088298
TI  - Implanon: a new implantable contraceptive.

PMID- 18088299
TI  - Safety in the NICU: preventing medication errors with computerized provider order
      entry.

PMID- 18088302
TI  - What can Trina teach us?

PMID- 18088303
TI  - Characterization of a Listeria monocytogenes protein interfering with Rab5a.
AB  - Listeria monocytogenes (LM) phagocytic strategy implies recruitment and
      inhibition of Rab5a. Here, we identify a Listeria protein that binds to Rab5a and
      is responsible for Rab5a recruitment to phagosomes and impairment of the GDP/GTP
      exchange activity. This protein was identified as a glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) from Listeria (p40 protein, Lmo 2459). The p40 protein was
      found within the phagosomal membrane. Analysis of the sequence of LM p40 protein
      revealed two enzymatic domains: the nicotinamide adenine dinucleotide (NAD)
      binding domain at the N-terminal and the C-terminal glycolytic domain. The
      putative ADP-ribosylating ability of this Listeria protein located in the N
      terminal domain was examined and showed some similarities to the activity and
      Rab5a inhibition exerted by Pseudomonas aeruginosa ExoS onto endosome-endosome
      fusion. Listeria p40 caused Rab5a-specific ADP ribosylation and blocked Rab5a
      exchange factor (Vps9) and GDI interaction and function, explaining the
      inhibition observed in Rab5a-mediated phagosome-endosome fusion. Meanwhile, ExoS
      impaired Rab5-early endosomal antigen 1 (EEA1) interaction and showed a wider Rab
      specificity. Listeria GAPDH might be the first intracellular gram-positive enzyme
      targeted to Rab proteins with ADP-ribosylating ability and a putative novel
      virulence factor.

PMID- 18088304
TI  - Plastid omega3-fatty acid desaturase-dependent accumulation of a systemic
      acquired resistance inducing activity in petiole exudates of Arabidopsis thaliana
      is independent of jasmonic acid.
AB  - Systemic acquired resistance (SAR) is an inducible defense mechanism that is
      activated throughout the plant, subsequent to localized inoculation with a
      pathogen. The establishment of SAR requires translocation of an unknown signal
      from the pathogen-inoculated leaf to the distal organs, where salicylic acid
      dependent defenses are activated. We demonstrate here that petiole exudates
      (PeXs) collected from Arabidopsis leaves inoculated with an avirulent (Avr)
      Pseudomonas syringae strain promote resistance when applied to Arabidopsis,
      tomato (Lycopersicum esculentum) and wheat (Triticum aestivum). Arabidopsis FATTY
      ACID DESATURASE7 (FAD7), SUPPRESSOR OF FATTY ACID DESATURASE DEFICIENCY1 (SFD1)
      and SFD2 genes are required for accumulation of the SAR-inducing activity. In
      contrast to Avr PeX from wild-type plants, Avr PeXs from fad7, sfd1 and sfd2
      mutants were unable to activate SAR when applied to wild-type plants. However,
      the SAR-inducing activity was reconstituted by mixing Avr PeXs collected from
      fad7 and sfd1 with Avr PeX from the SAR-deficient dir1 mutant. Since FAD7, SFD1
      and SFD2 are involved in plastid glycerolipid biosynthesis and SAR is also
      compromised in the Arabidopsis monogalactosyldiacylglycerol synthase1 mutant we
      suggest that a plastid glycerolipid-dependent factor is required in Avr PeX along
      with the DIR1-encoded lipid transfer protein for long-distance signaling in SAR.
      FAD7-synthesized lipids provide fatty acids for synthesis of jasmonic acid (JA).
      However, co-infiltration of JA and methylJA with Avr PeX from fad7 and sfd1 did
      not reconstitute the SAR-inducing activity. In addition, JA did not co-purify
      with the SAR-inducing activity confirming that JA is not the mobile signal in
      SAR.

PMID- 18088305
TI  - Combinatorial interactions of multiple cis-elements regulating the induction of
      the Arabidopsis XERO2 dehydrin gene by abscisic acid and cold.
AB  - Multiple combinations of mutations in the promoter of the XERO2 dehydrin gene
      were used to identify elements involved in ABA and cold induction. Mutating one
      of the three ACGT elements (ACGT1) increases expression in the absence of cold or
      ABA. An AT-rich element is a novel partner (coupling element) of ACGT-containing
      ABA-responsive cis-elements. A 12-bp palindrome also acts as a coupling element
      for ABA induction and includes one of the three dehydration-responsive element/C
      repeat (DRE/CRT) elements and two overlapping motifs (TGTCG and TCGGC) previously
      shown to be statistically enriched in ABA-dependent and 'VP1 or ABA'-dependent
      activated genes (Plant Physiol. 2005; 139:437). At least two of the DRE/CRT
      elements are required for significant cold induction. During cold induction the
      AT-rich element also functions as a coupling element and ACGT1 is involved in
      repressing this induction. Two of the ACGT and DRE/CRT elements overlap, and
      mutating a single base in the ACGT of either of the two GCCGACGT sequences while
      retaining a DRE element reduced both ABA and cold induction. Changing the spatial
      relationships between the elements by deletion, inversion or insertion of DNA
      sequences reduced both cold and ABA induction. Overexpression of CBF1, -2 or -3
      induced XERO2 expression in untreated plants. The ABI5 transcription factor may
      have a role in ABA-induced XERO2 expression, whereas ABI3 and ABI4 do not. The
      GCA2 gene was essential for both cold and ABA induction. A combination of the
      same overlapping and shared elements is used in the regulation of transcription
      by ABA and cold.

PMID- 18088306
TI  - Partial demethylation of oligogalacturonides by pectin methyl esterase 1 is
      required for eliciting defence responses in wild strawberry (Fragaria vesca).
AB  - In addition to the role of the cell wall as a physical barrier against pathogens,
      some of its constituents, such as pectin-derived oligogalacturonides (OGA), are
      essential components for elicitation of defence responses. To investigate how
      modifications of pectin alter defence responses, we expressed the fruit-specific
      Fragaria x ananassa pectin methyl esterase FaPE1 in the wild strawberry Fragaria
      vesca. Pectin from transgenic ripe fruits differed from the wild-type with regard
      to the degree and pattern of methyl esterification, as well as the average size
      of pectin polymers. Purified oligogalacturonides from the transgenic fruits
      showed a reduced degree of esterification compared to oligogalacturonides from
      wild-type fruits. This reduced esterification is necessary to elicit defence
      responses in strawberry. The transgenic F. vesca lines had constitutively
      activated pathogen defence responses, resulting in higher resistance to the
      necrotropic fungus Botrytis cinerea. Further studies in F. vesca and Nicotiana
      benthamiana leaves showed that the elicitation capacity of the
      oligogalacturonides is more specific than previously envisaged.

PMID- 18088308
TI  - Degradation of the auxin response factor ARF1.
AB  - Auxin-mediated gene expression is largely controlled through a family of DNA
      binding proteins known as auxin response factors (ARF). Previous studies on the
      role of proteolytic regulation in auxin signaling have focused on degradation of
      their interacting partner, the Aux/IAA proteins. Aux/IAA family members with
      domain II sequences are rapidly degraded, show auxin-enhanced degradation rates,
      and interact with the related F-box proteins TIR1 and AFB1-3, which indicates
      that they are ubiquitylated by a CUL1-dependent E3 ligase. To date, limited data
      have been generated regarding degradation of ARFs. Here, we focus on the
      degradation rate of one ARF family member, Arabidopsis thaliana ARF1, and find
      that the half-lives of N-terminally HA-tagged ARF1 and C-terminally luciferase
      tagged ARF1 are both approximately 3-4 h. This half-life appears to be conferred
      by a component of the middle region (MR), and degradation of the luciferase
      fusion with the MR is more rapid when the fusion includes an additional nuclear
      localization signal. ARF1 degradation is proteasome-dependent and rates are not
      altered in a CUL1 mutant background, suggesting that this ARF is targeted for
      proteasomal degradation via an alternative set of machinery to that used for
      Aux/IAA degradation. Consistent with this, exogenous indole acetic acid does not
      affect the degradation of ARF1. Given increasing evidence that the relative ratio
      of Aux/IAAs to ARFs rather than the absolute quantity within the cell appears to
      be the mode through which auxin signaling is modulated, this half-life is likely
      to be biologically relevant.

PMID- 18088307
TI  - Interplay between JA, SA and ABA signalling during basal and induced resistance
      against Pseudomonas syringae and Alternaria brassicicola.
AB  - We have examined the role of the callose synthase PMR4 in basal resistance and
      beta-aminobutyric acid-induced resistance (BABA-IR) of Arabidopsis thaliana
      against the hemi-biotrophic pathogen Pseudomonas syringae and the necrotrophic
      pathogen Alternaria brassicicola. Compared to wild-type plants, the pmr4-1 mutant
      displayed enhanced basal resistance against P. syringae, which correlated with
      constitutive expression of the PR-1 gene. Treating the pmr4-1 mutant with BABA
      boosted the already elevated levels of PR-1 gene expression, and further
      increased the level of resistance. Hence, BABA-IR against P. syringae does not
      require PMR4-derived callose. Conversely, pmr4-1 plants showed enhanced
      susceptibility to A. brassicicola, and failed to show BABA-IR. Wild-type plants
      showing BABA-IR against A. brassicicola produced increased levels of JA. The pmr4
      1 mutant produced less JA upon A. brassicicola infection than the wild-type.
      Blocking SA accumulation in pmr4-1 restored basal resistance, but not BABA-IR
      against A. brassicicola. This suggests that the mutant's enhanced susceptibility
      to A. brassicicola is caused by SA-mediated suppression of JA, whereas the lack
      of BABA-IR is caused by its inability to produce callose. A. brassicicola
      infection suppressed ABA accumulation. Pre-treatment with BABA antagonized this
      ABA accumulation, and concurrently potentiated expression of the ABA-responsive
      ABI1 gene. Hence, BABA prevents pathogen-induced suppression of ABA accumulation,
      and sensitizes the tissue to ABA, causing augmented deposition of PMR4-derived
      callose.

PMID- 18088309
TI  - GASSHO1 and GASSHO2 encoding a putative leucine-rich repeat transmembrane-type
      receptor kinase are essential for the normal development of the epidermal surface
      in Arabidopsis embryos.
AB  - Receptor-like kinases (RLKs) containing leucine-rich repeats (LRRs) act as both
      signal receptor and signal transducer in ligand-mediated communication between
      cells. It is believed that many LRR-RLKs are present in the Arabidopsis genome,
      but the functions of most are unknown. We recently identified Bnms4D-82, an
      expressed sequence tag (EST) in Brassica napus that encodes an LRR-RLK and is
      expressed at an early stage of its microspore embryogenesis. To elucidate the
      function of this gene we used GASSHO1 (GSO1) and GSO2, two Arabidopsis genes with
      a high degree of homology with Bnms4D-82. The products of transcripts of GSO1 and
      GSO2 accumulate in parts of the embryo and in seedlings, but not in true leaves.
      Plants that lacked both GSO1 and GSO2 exhibited pleiotropy, including abnormal
      bending of embryos, ectopic adhesion between cotyledons, a highly permeable
      epidermal structure, and an abnormal pattern of distribution of stomata on
      cotyledons in embryos and seedlings. However, plants homozygous for either gso1-1
      or gso2-1 had no visible abnormality. These results suggest that GASSHO genes are
      essential for the formation of a normal epidermal surface during embryogenesis.

PMID- 18088310
TI  - Extrachromosomal circular DNA derived from tandemly repeated genomic sequences in
      plants.
AB  - Extrachromosomal circular DNA (eccDNA) is one characteristic of the plasticity of
      the eukaryotic genome. It was found in various non-plant organisms from yeast to
      humans. EccDNA is heterogeneous in size and contains sequences derived primarily
      from repetitive chromosomal DNA. Here, we report the occurrence of eccDNA in
      small and large genome plant species, as identified using two-dimensional gel
      electrophoresis. We show that eccDNA is readily detected in both Arabidopsis
      thaliana and Brachycome dichromosomatica, reflecting a normal phenomenon that
      occurs in wild-type plants. The size of plant eccDNA ranges from > 2 kb to < 20
      kb, which is similar to the sizes found in other organisms. These DNA molecules
      correspond to 5S ribosomal DNA (rDNA), non-coding chromosomal high-copy tandem
      repeats and telomeric DNA of both species. Circular multimers of the repeating
      unit of 5S rDNA were identified in both species. In addition, similar multimers
      were also demonstrated with the B. dichromosomatica repetitive element Bdm29.
      Such circular multimers of tandem repeats were found in animal models, suggesting
      a common mechanism for eccDNA formation among eukaryotes. This mechanism may
      involve looping-out via intrachromosomal homologous recombination. The
      implications of these results on genome plasticity and evolutionary processes are
      discussed.

PMID- 18088311
TI  - The AT-hook-containing proteins SOB3/AHL29 and ESC/AHL27 are negative modulators
      of hypocotyl growth in Arabidopsis.
AB  - SOB3, which encodes a plant-specific AT-hook motif containing protein, was
      identified from an activation-tagging screen for suppressors of the long
      hypocotyl phenotype of a weak phyB allele, phyB-4. sob3-D (suppressor of phyB-4#3
      dominant) overexpressing seedlings have shorter hypocotyls, and as adults develop
      larger flowers and leaves, and are delayed in senescence compared with wild-type
      plants. At the nucleotide level, SOB3 is closely related to ESCAROLA (ESC), which
      was identified in an independent activation-tagging screen. ESC overexpression
      also suppresses the phyB-4 long-hypocotyl phenotype, and confers an adult
      morphology similar to sob3-D, suggesting similar functions. Analysis of
      transgenic plants harboring SOB3:SOB3-GUS or ESC:ESC-GUS translational fusions,
      driven by their endogenous promoter regions, showed GUS activity in the hypocotyl
      and vasculature tissue in light- and dark-grown seedlings. A loss-of-function
      SOB3 allele (sob3-4) was generated through an ethyl methanesulfonate intragenic
      suppressor screen of sob3-D phyB-4 plants, and this allele was combined with a
      predicted null allele, disrupting ESC (esc-8), to examine potential genetic
      interactions. The sob3-4 esc-8 double mutant had a long hypocotyl in multiple
      fluence rates of continuous white, far-red, red and blue light. sob3-4 esc-8 phyB
      9 and sob3-4 esc-8 cry-103 triple mutants also had longer hypocotyls than
      photoreceptor single mutants. In contrast, the sob3-4 esc-8 phyA-211 triple
      mutant was the same length as phyA-211 single mutants. Taken together, these data
      indicate that SOB3 and ESC act redundantly to modulate hypocotyl growth
      inhibition in response to light.

PMID- 18088312
TI  - Monitoring changes in alternative precursor messenger RNA splicing in multiple
      gene transcripts.
AB  - Alternative splicing (AS) increases the proteomic and functional capacity of
      genomes through the generation of alternative mRNA transcripts from the same
      gene. AS is now estimated to occur in a third of Arabidopsis and rice genes, and
      includes genes involved in the control of growth and development, responses to
      stress and signalling. Regulation of AS reflects the interactions between
      positive and negative cis sequences in the precursor messenger RNA and a range of
      trans-acting factors. The levels and activities of these factors differ in
      different cells and growth conditions. To identify changes in AS in multiple
      genes simultaneously, we have established a reproducible RT-PCR panel that can
      analyse 96 alternative splicing events and accurately measure the ratio of
      alternatively spliced products. This procedure detected statistically significant
      changes in AS in different plant organs, in plants grown under different light
      and day-length conditions, and in plants overexpressing splicing factors. The
      system provides a convenient, medium-throughput means of monitoring changes in AS
      in multiple genes. It can readily be applied to much larger or targeted sets of
      gene transcripts to generate information on the significance and regulation of AS
      in plant growth and development, specific processes and responses to external
      stimuli.

PMID- 18088313
TI  - Functional divergence of the duplicated AtKIN14a and AtKIN14b genes: critical
      roles in Arabidopsis meiosis and gametophyte development.
AB  - Gene duplication is important for gene family evolution, allowing for functional
      divergence and innovation. In flowering plants, duplicated genes are widely
      observed, and functional redundancy of closely related duplicates has been
      reported, but few cases of functional divergence of close duplicates have been
      described. Here, we show that the Arabidopsis AtKIN14a and AtKIN14b genes
      encoding highly similar kinesins are two of the most closely related Arabidopsis
      paralogs, which were formed by a duplication event that occurred after the split
      of Arabidopsis and poplar. In addition, AtKIN14a and AtKIN14b exhibit varying
      degrees of coding sequence divergence. Further genetic studies of plants carrying
      atkin14a and/or atkin14b mutations indicate that, although these two genes have
      similar functions, there is clear evidence for functional divergence. Although
      both genes are important for male and female meiosis, AtKIN14a plays a more
      critical role in male meiosis than AtKIN14b. Moreover, either one of these two
      genes is necessary and sufficient for gametophyte development, indicating that
      they are redundant for this function. Therefore, AtKIN14a and AtKIN14b together
      play important roles in controlling plant reproductive development. Our results
      suggest that the AtKIN14a and AtKIN14b genes have retained similar functions in
      gametophyte development and female meiosis, but have evolved partially distinct
      functions in male meiosis, with AtKIN14a playing a more substantive role.

PMID- 18088314
TI  - Evidence of multiple horizontal transfers of the long terminal repeat
      retrotransposon RIRE1 within the genus Oryza.
AB  - Horizontal gene transfer, defined as the transmission of genetic material between
      reproductively isolated species, has been considered for a long time to be a rare
      phenomenon. Most well-documented cases of horizontal gene transfer have been
      described in prokaryotes or in animals and they often involve transposable
      elements. The most abundant class of transposable elements in plant genomes are
      the long terminal repeat (LTR) retrotransposons. Because of their propensity to
      increase their copy number while active, LTR retrotransposons can have a
      significant impact on genomics changes during evolution. In a previous study, we
      showed that in the wild rice species Oryza australiensis, 60% of the genome is
      composed of only three families of LTR retrotransposons named RIRE1, Wallabi and
      Kangourou. In the present study, using both in silico and experimental
      approaches, we show that one of these three families, RIRE1, has been transferred
      horizontally between O. australiensis and seven other reproductively isolated
      Oryza species. This constitutes a new case of horizontal transfer in plants.

PMID- 18088315
TI  - The sucrose regulated transcription factor bZIP11 affects amino acid metabolism
      by regulating the expression of ASPARAGINE SYNTHETASE1 and PROLINE
      DEHYDROGENASE2.
AB  - Translation of the transcription factor bZIP11 is repressed by sucrose in a
      process that involves a highly conserved peptide encoded by the 5' leaders of
      bZIP11 and other plant basic region leucine zipper (bZip) genes. It is likely
      that a specific signaling pathway operating at physiological sucrose
      concentrations controls metabolism via a feedback mechanism. In this paper bZIP11
      target processes are identified using transiently increased nuclear bZIP11 levels
      and genome-wide expression analysis. bZIP11 affects the expression of hundreds of
      genes with proposed functions in biochemical pathways and signal transduction.
      The expression levels of approximately 80% of the genes tested are not affected
      by bZIP11 promoter-mediated overexpression of bZIP11. This suggests that <20% of
      the identified genes appear to be physiologically relevant targets of bZIP11.
      ASPARAGINE SYNTHETASE1 and PROLINE DEHYDROGENASE2 are among the rapidly activated
      bZIP11 targets, whose induction is independent of protein translation. Transient
      expression experiments in Arabidopsis protoplasts show that the bZIP11-dependent
      activation of the ASPARAGINE SYNTHETASE1 gene is dependent on a G-box element
      present in the promoter. Increased bZIP11 expression leads to decreased proline
      and increased phenylalanine levels. A model is proposed in which sugar signals
      control amino acid levels via the bZIP11 transcription factor.

PMID- 18088316
TI  - A cysteine-rich receptor-like kinase NCRK and a pathogen-induced protein kinase
      RBK1 are Rop GTPase interactors.
AB  - In plants, Rop/Rac GTPases have emerged as central regulators of diverse
      signalling pathways in plant growth and pathogen defence. When active, they
      interact with a wide range of downstream effectors. Using yeast two-hybrid
      screening we have found three previously uncharacterized receptor-like protein
      kinases to be Rop GTPase-interacting molecules: a cysteine-rich receptor kinase,
      named NCRK, and two receptor-like cytosolic kinases from the Arabidopsis RLCK-VIb
      family, named RBK1 and RBK2. Uniquely for Rho-family small GTPases, plant Rop
      GTPases were found to interact directly with the protein kinase domains. Rop4
      bound NCRK preferentially in the GTP-bound conformation as determined by flow
      cytometric fluorescence resonance energy transfer measurements in insect cells.
      The kinase RBK1 did not phosphorylate Rop4 in vitro, suggesting that the protein
      kinases are targets for Rop signalling. Bimolecular fluorescence complementation
      assays demonstrated that Rop4 interacted in vivo with NCRK and RBK1 at the plant
      plasma membrane. In Arabidopsis protoplasts, NCRK was hyperphosphorylated and
      partially co-localized with the small GTPase RabF2a in endosomes. Gene expression
      analysis indicated that the single-copy NCRK gene was relatively upregulated in
      vasculature, especially in developing tracheary elements. The seven Arabidopsis
      RLCK-VIb genes are ubiquitously expressed in plant development, and highly so in
      pollen, as in case of RBK2. We show that the developmental context of RBK1 gene
      expression is predominantly associated with vasculature and is also locally
      upregulated in leaves exposed to Phytophthora infestans and Botrytis cinerea
      pathogens. Our data indicate the existence of cross-talk between Rop GTPases and
      specific receptor-like kinases through direct molecular interaction.

PMID- 18088317
TI  - RACK1 regulates the cell surface expression of the G protein-coupled receptor for
      thromboxane A(2).
AB  - We used the yeast two-hybrid system to screen for proteins that interact with the
      C-terminus of the beta isoform of the thromboxane A(2) receptor (TPbeta). This
      screen identified receptor for activated C-kinase 1 (RACK1) as a new TPbeta
      interacting protein. Here, we show that RACK1 directly binds to the C-terminus
      and the first intracellular loop of TPbeta. The TPbeta-RACK1 association was
      further confirmed by co-immunoprecipitation studies in HEK293 cells and was not
      modulated by stimulation of the receptor. We observed that cell surface
      expression of TPbeta was increased when RACK1 was overexpressed, while it was
      inhibited when endogenous RACK1 expression was knocked down by small interfering
      RNA. Confocal microscopy confirmed the impaired cell surface expression of TPbeta
      and suggested that the receptors remained predominantly localized in the
      endoplasmic reticulum (ER) in RACK1-depleted cells. Confocal microscopy also
      revealed that a transient TPbeta-RACK1 association takes place in the ER. The
      effect of RACK1 on receptor trafficking to the cell surface appears to be
      selective to some G protein-coupled receptors (GPCRs) because inhibition of RACK1
      expression also affected cell surface targeting of the angiotensin II type 1
      receptor and CXCR4 but not of beta(2)-adrenergic and prostanoid DP receptors. Our
      data demonstrate for the first time a direct interaction between RACK1 and a GPCR
      and identify a novel role for RACK1 in the regulation of the transport of a
      membrane receptor from the ER to the cell surface.

PMID- 18088318
TI  - Distinct motifs of neuropeptide Y receptors differentially regulate trafficking
      and desensitization.
AB  - Activated human neuropeptide Y Y(1) receptors rapidly desensitize and internalize
      through clathrin-coated pits and recycle from early and recycling endosomes,
      unlike Y(2) receptors that neither internalize nor desensitize. To identify
      motifs implicated in Y(1) receptor desensitization and trafficking, mutants with
      varying C-terminal truncations or a substituted Y(2) C-terminus were constructed.
      Point mutations of key putative residues were made in a C-terminal conserved
      motif [phi-H-(S/T)-(E/D)-V-(S/T)-X-T] that we have identified and in the second
      intracellular i2 loop. Receptors were analyzed by functional assays,
      spectrofluorimetric measurements on living cells, flow cytometry, confocal
      imaging and bioluminescence resonance energy transfer assays for beta-arrestin
      activation and adaptor protein (AP-2) complex recruitment. Inhibitory GTP-binding
      protein-dependent signaling of Y(1) receptors to adenylyl cyclase and
      desensitization was unaffected by C-terminal truncations or mutations, while C
      terminal deletion mutants of 42 and 61 amino acids no longer internalized.
      Substitutions of Thr357, Asp358, Ser360 and Thr362 by Ala in the C-terminus
      abolished both internalization and beta-arrestin activation but not
      desensitization. A Pro145 substitution by His in an i2 consensus motif reported
      to mediate phosphorylation-independent recruitment of beta-arrestins affected
      neither desensitization, internalization or recycling kinetics of activated Y(1)
      receptors nor beta-arrestin activation. Interestingly, combining Pro145
      substitution by His and C-terminal substitutions significantly attenuates Y(1)
      desensitization. In the Y(2) receptor, replacement of His155 with Pro at this
      position in the i2 loop motif promotes agonist-mediated desensitization, beta
      arrestin activation, internalization and recycling. Overall, our results indicate
      that beta-arrestin-mediated desensitization and internalization of Y(1) and Y(2)
      receptors are differentially regulated by the C-terminal motif and the i2 loop
      consensus motif.

PMID- 18088319
TI  - How many ways through the Golgi maze?
AB  - The secretory route in eukaryotic cells has been regarded as one common pathway
      from the endoplasmic reticulum (ER) through the Golgi cisternae to the trans
      Golgi network where recognition, sorting and exit of cargo molecules are thought
      to occur. Morphologically, the ribosome-coated ER is observed throughout the
      cytoplasm, while the Golgi apparatus usually is confined to a perinuclear
      position in mammalian cells. However, Golgi outposts have been observed in
      neuronal dendrites and dispersed Golgi elements in skeletal muscle myofibers. In
      insects, like in Drosophila melanogaster imaginal disc cells and epidermal cells
      of Tobacco and Arabidopsis leafs, individual Golgi stacks are distributed
      throughout the cytoplasm. Golgi stacks do not only differ in their intracellular
      localization but also in the number of stacks from one to several hundreds. Each
      stack consists of closely aligned, flattened, membrane-limited cisternae. The
      number of cisternae in a Golgi stack is also variable, 2-3 in some ciliates, 10
      in many plant cell types and up to 30 in certain euglenoids. The yeast
      Saccharomyces cerevisiae has a Golgi structure of minimal complexity with
      scattered solitary cisternae. It is assumed that the number of Golgi cisternae
      reflects the overall complexity of the enzymatic reactions that occur in their
      lumen, while the number of stacks reflects the load of macromolecules arriving at
      the cis side. In this review, we will focus on how the available morphological
      and biochemical data fit with the current view of protein sorting in the
      secretory pathway, particularly in polarized cells like neuronal and epithelial
      cells.

PMID- 18088320
TI  - Imaging of lipid biosynthesis: how a neutral lipid enters lipid droplets.
AB  - The biosynthesis and storage of triglyceride (TG) is an important cellular
      process conserved from yeast to man. Most mammalian cells accumulate TG in lipid
      droplets, most prominent in adipocytes, which are specialized to store large
      amounts of the TG over long periods. In this study, we followed TG biosynthesis
      and targeting by fluorescence imaging in living 3T3-L1 adipocytes and COS7
      fibroblasts. Key findings were (i) not only TG but also its direct metabolic
      precursor diacylglycerol, DG, accumulates on lipid droplets; (ii) the essential
      enzyme diacylglycerol acyltransferase 2 associates specifically with lipid
      droplets where it catalyzes the conversion of DG to TG and (iii) individual lipid
      droplets within one cell acquire TG at very different rates, suggesting unequal
      access to the biosynthetic machinery. We conclude that at least part of TG
      biosynthesis takes place in the immediate vicinity of lipid droplets. In vitro
      assays on purified lipid droplets show that this fraction of the biosynthetic TG
      is directly inserted into the growing droplet.

PMID- 18088321
TI  - Structure of Vps26B and mapping of its interaction with the retromer protein
      complex.
AB  - Retromer is a heteromeric protein complex with important roles in endosomal
      membrane trafficking, most notably in the retrograde transport of lysosomal
      hydrolase receptors from endosomes to the Golgi. The core of retromer is composed
      of three subunits vacuolar protein sorting (Vps)35, Vps26 and Vps29, and in
      mammals, there are two paralogues of the medium subunit Vps26A and Vps26B. We
      find that both Vps26A and Vps26B bind to Vps35/Vps29 with nanomolar affinity and
      compete for a single-binding site to define distinct retromer complexes in vitro
      and in vivo. We have determined the crystal structure of mouse Vps26B and compare
      this structure with that of Vps26A. Vps26 proteins have a striking similarity to
      the arrestin family of proteins that regulate the signalling and endocytosis of G
      protein-coupled receptors, although we observe that surface residues involved in
      arrestin function are not conserved in Vps26. Using structure-based mutagenesis,
      we show that both Vps26A and Vps26B are incorporated into retromer complexes
      through binding of Vps35 to a highly conserved surface patch within the C
      terminal subdomain and that this interaction is required for endosomal
      recruitment of the proteins.

PMID- 18088322
TI  - The tail that wags the dog: the globular tail domain defines the function of
      myosin V/XI.
AB  - Actin-based organelle movements are driven by the related multifunctional myosin
      motors of class V in animals and fungi and class XI in plants. The versatility of
      these motors depends critically on their C-terminal globular tail domain that
      allows them to bind to a broad variety of cargo molecules. Regulation of this
      motor-cargo attachment is frequently employed to modulate organelle movement.
      While the overall structure of the cargo-binding globular tail appears to be
      conserved between myosin V and XI, it has become apparent that the motor-cargo
      interactions differ widely even within a single organism and involve protein
      complexes with different architecture and completely unrelated protein domains.
      At the same time, indirect evidence suggests that adaptor or receptor
      dimerization could facilitate efficient myosin capture. Comparison of myosin V
      and XI across the large evolutionary distance between animals and plants will
      likely reveal more fundamental insights into these important motors.

PMID- 18088323
TI  - SNX1 defines an early endosomal recycling exit for sortilin and mannose 6
      phosphate receptors.
AB  - Mannose-6-phosphate receptors (MPRs) transport lysosomal hydrolases from the
      trans Golgi network (TGN) to endosomes. Recently, the multi-ligand receptor
      sortilin has also been implicated in this transport, but the transport carriers
      involved herein have not been identified. By quantitative immuno-electron
      microscopy, we localized endogenous sortilin of HepG2 cells predominantly to the
      TGN and endosomes. In the TGN, sortilin colocalized with MPRs in the same
      clathrin-coated vesicles. In endosomes, sortilin and MPRs concentrated in sorting
      nexin 1 (SNX1)-positive buds and vesicles. SNX1 depletion by small interfering
      RNA resulted in decreased pools of sortilin in the TGN and an increase in
      lysosomal degradation. These data indicate that sortilin and MPRs recycle to the
      TGN in SNX1-dependent carriers, which we named endosome-to-TGN transport carriers
      (ETCs). Notably, ETCs emerge from early endosomes (EE), lack recycling plasma
      membrane proteins and by three-dimensional electron tomography exhibit unique
      structural features. Hence, ETCs are distinct from hitherto described EE-derived
      membranes involved in recycling. Our data emphasize an important role of EEs in
      recycling to the TGN and indicate that different, specialized exit events occur
      on the same EE vacuole.

PMID- 18088324
TI  - Dynamin-dependent biogenesis, cell cycle regulation and mitochondrial association
      of peroxisomes in fission yeast.
AB  - Peroxisomes were visualized for the first time in living fission yeast cells. In
      small, newly divided cells, the number of peroxisomes was low but increased in
      parallel with the increase in cell length/volume that accompanies cell cycle
      progression. In cells grown in oleic acid, both the size and the number of
      peroxisomes increased. The peroxisomal inventory of cells lacking the dynamin
      related proteins Dnm1 or Vps1 was similar to that in wild type. By contrast,
      cells of the double mutant dnm1Delta vps1Delta contained either no peroxisomes at
      all or a small number of morphologically aberrant organelles. Peroxisomes
      exhibited either local Brownian movement or longer-range linear displacements,
      which continued in the absence of either microtubules or actin filaments. On the
      contrary, directed peroxisome motility appeared to occur in association with
      mitochondria and may be an indirect function of intrinsic mitochondrial dynamics.
      We conclude that peroxisomes are present in fission yeast and that Dnm1 and Vps1
      act redundantly in peroxisome biogenesis, which is under cell cycle control.
      Peroxisome movement is independent of the cytoskeleton but is coupled to
      mitochondrial dynamics.

PMID- 18088325
TI  - The twists and turns of Maurer's cleft trafficking in P. falciparum-infected
      erythrocytes.
AB  - The malaria parasite, Plasmodium falciparum, invades the red blood cells (RBCs)
      of its human host and initiates a series of morphological rearrangements within
      the host cell cytoplasm. The mature RBC has no endogenous trafficking machinery;
      therefore, the parasite generates novel structures to mediate protein transport.
      These include compartments called the Maurer's clefts (MC), which play an
      important role in the trafficking of parasite proteins to the surface of the host
      cell. Recent electron tomography studies have revealed MC as convoluted flotillas
      of flattened discs that are tethered to the RBC membrane, prompting speculation
      that the MC could, in one respect, represent an extracellular equivalent of the
      Golgi apparatus. Visualization of both resident and cargo proteins has helped
      decipher the signals and routes for trafficking of parasite proteins to the MC
      and beyond.

PMID- 18088326
TI  - Evidence for chloroplast control of external Ca2+-induced cytosolic Ca2+
      transients and stomatal closure.
AB  - The role of guard cell chloroplasts in stomatal function is controversial. It is
      usually assumed that stomatal closure is preceded by a transient increase in
      cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) in the guard cells. Here, we
      provide the evidence that chloroplasts play a critical role in the generation of
      extracellular Ca(2+) ([Ca(2+)](ext))-induced [Ca(2+)](cyt) transients and
      stomatal closure in Arabidopsis. CAS (Ca(2+) sensing receptor) is a plant
      specific putative Ca(2+)-binding protein that was originally proposed to be a
      plasma membrane-localized external Ca(2+) sensor. In the present study, we
      characterized the intracellular localization of CAS in Arabidopsis with a
      combination of techniques, including (i) in vivo localization of green
      fluorescent protein (GFP) fused gene expression, (ii) subcellular fractionation
      and fractional analysis of CAS with Western blots, and (iii) database analysis of
      thylakoid membrane proteomes. Each technique produced consistent results. CAS was
      localized mainly to chloroplasts. It is an integral thylakoid membrane protein,
      and the N-terminus acidic Ca(2+)-binding region is likely exposed to the stromal
      side of the membrane. The phenotype of T-DNA insertion CAS knockout mutants and
      cDNA mutant-complemented plants revealed that CAS is essential for stomatal
      closure induced by external Ca(2+). In contrast, overexpression of CAS promoted
      stomatal closure in the absence of externally applied Ca(2+). Furthermore, using
      the transgenic aequorin system, we showed that [Ca(2+)](ext)-induced
      [Ca(2+)](cyt) transients were significantly reduced in CAS knockout mutants. Our
      results suggest that thylakoid membrane-localized CAS is essential for
      [Ca(2+)](ext)-induced [Ca(2+)](cyt) transients and stomatal closure.

PMID- 18088327
TI  - Restricting glutathione biosynthesis to the cytosol is sufficient for normal
      plant development.
AB  - Glutathione (GSH) homeostasis in plants is essential for cellular redox control
      and efficient responses to abiotic and biotic stress. Compartmentation of the GSH
      biosynthetic pathway is a unique feature of plants. The first enzyme, gamma
      glutamate cysteine ligase (GSH1), responsible for synthesis of gamma
      glutamylcysteine (gamma-EC), is, in Arabidopsis, exclusively located in the
      plastids, whereas the second enzyme, glutathione synthetase (GSH2), is located in
      both plastids and cytosol. In Arabidopsis, gsh2 insertion mutants have a seedling
      lethal phenotype in contrast to the embryo lethal phenotype of gsh1 null mutants.
      This difference in phenotype may be due to partial replacement of GSH functions
      by gamma-EC, which in gsh2 mutants hyperaccumulates to levels 5000-fold that in
      the wild type and 200-fold wild-type levels of GSH. In situ labelling of thiols
      with bimane and confocal imaging in combination with HPLC analysis showed high
      concentrations of gamma-EC in the cytosol. Feedback inhibition of Brassica juncea
      plastidic GSH1 by gamma-EC in vitro strongly suggests export of gamma-EC as
      functional explanation for hyperaccumulation. Complementation of gsh2 mutants
      with the cytosol-specific GSH2 gave rise to phenotypically wild-type transgenic
      plants. These results support the conclusion that cytosolic synthesis of GSH is
      sufficient for plant growth. The transgenic lines further show that, consistent
      with the exclusive plastidic localization of GSH1, gamma-EC is exported from the
      plastids to supply the cytosol with the immediate precursor for GSH biosynthesis,
      and that there can be efficient re-import of GSH into the plastids to allow
      effective control of GSH biosynthesis through feedback inhibition of GSH1.

PMID- 18088328
TI  - Short-term responses of leaf growth rate to water deficit scale up to whole-plant
      and crop levels: an integrated modelling approach in maize.
AB  - Physiological and genetic studies of leaf growth often focus on short-term
      responses, leaving a gap to whole-plant models that predict biomass accumulation,
      transpiration and yield at crop scale. To bridge this gap, we developed a model
      that combines an existing model of leaf 6 expansion in response to short-term
      environmental variations with a model coordinating the development of all leaves
      of a plant. The latter was based on: (1) rates of leaf initiation, appearance and
      end of elongation measured in field experiments; and (2) the hypothesis of an
      independence of the growth between leaves. The resulting whole-plant leaf model
      was integrated into the generic crop model APSIM which provided dynamic feedback
      of environmental conditions to the leaf model and allowed simulation of crop
      growth at canopy level. The model was tested in 12 field situations with
      contrasting temperature, evaporative demand and soil water status. In observed
      and simulated data, high evaporative demand reduced leaf area at the whole-plant
      level, and short water deficits affected only leaves developing during the
      stress, either visible or still hidden in the whorl. The model adequately
      simulated whole-plant profiles of leaf area with a single set of parameters that
      applied to the same hybrid in all experiments. It was also suitable to predict
      biomass accumulation and yield of a similar hybrid grown in different conditions.
      This model extends to field conditions existing knowledge of the environmental
      controls of leaf elongation, and can be used to simulate how their genetic
      controls flow through to yield.

PMID- 18088329
TI  - Comparing model predictions and experimental data for the response of stomatal
      conductance and guard cell turgor to manipulations of cuticular conductance, leaf
      to-air vapour pressure difference and temperature: feedback mechanisms are able
      to account for all observations.
AB  - Stomata respond to increasing leaf-to-air vapour pressure difference (LAVPD) (D)
      by closing. The mechanism by which this occurs is debated. A role for feedback
      and peristomatal transpiration has been proposed. In this paper, we apply a
      recent mechanistic model of stomatal behaviour, and compare model and
      experimental data for the influence of increasing D on stomatal conductance. We
      manipulated cuticular conductance (g(c)) by three independent methods. First, we
      increased g(c) by using a solvent mixture applied to both leaf surfaces prior to
      determining stomatal responses to D; second, we increased g(c) by increasing leaf
      temperature at constant D; and third, we coated a small area of leaf with a light
      oil to decrease g(c). In all three experiments, experimental data and model
      outputs showed very close agreement. We conclude, from the close agreement
      between model and experimental data and the fact that manipulations of g(c), and
      hence cuticular transpiration, influenced g(s) in ways consistent with a feedback
      mechanism, that feedback is central in determining stomatal responses to D.

PMID- 18088330
TI  - Metabolomic and proteomic changes in the xylem sap of maize under drought.
AB  - Plants produce compounds in roots that are transported to shoots via the xylem
      sap. Some of these compounds are vital for signalling and adaptation to
      environmental stress such as drought. In this study, we screened the xylem sap
      using mass spectrometry to quantify the changes in new and previously identified
      sap constituents under extended drought. We detected and quantified the changes
      in the concentration of 31 compounds present in the xylem sap under progressively
      increasing drought stress. We found changes in the hormones abscisic acid (ABA)
      and cytokinin, and the presence of high concentrations of the aromatic cytokinin
      6-benzylaminopurine (BAP). Several phenylpropanoid compounds (coumaric, caffeic
      and ferulic acids) were found in xylem sap. The concentrations of some of these
      phenylpropanoid compounds changed under drought. In parallel, an analysis of the
      xylem sap proteome was conducted. We found a higher abundance of cationic
      peroxidases, which with the increase in phenylpropanoids may lead to a reduction
      in lignin biosynthesis in the xylem vessels and could induce cell wall
      stiffening. The application of new methodologies provides insights into the range
      of compounds in sap and how alterations in composition may lead to changes in
      development and signalling during adaptation to drought.

PMID- 18088331
TI  - Phosphatidylinositol 3- and 4-phosphate modulate actin filament reorganization in
      guard cells of day flower.
AB  - Phosphatidylinositol 3-kinases (PtdIns 3-kinases) that produce
      phosphatidylinositol (3,4,5) triphosphate (PtdIns(3,4,5)P(3)) are considered to
      be important regulators of actin dynamics in animal cells. In plants, neither
      PtdIns(3,4,5)P(3) nor the enzyme that produces this lipid has been reported.
      However, a PtdIns 3-kinase that produces phosphatidylinositol 3-phosphate
      (PtdIns3P) has been identified, suggesting that PtdIns3P, instead of
      PtdIns(3,4,5)P(3), regulates actin dynamics in plant cells. Phosphatidylinositol
      4-kinase (PtdIns 4-kinase) is closely associated with the actin cytoskeleton in
      plant cells, suggesting a role for this lipid kinase and its product
      phosphatidylinositol 4-phosphate (PtdIns4P) in actin-related processes. Here, we
      investigated whether or not PtdIns3P or PtdIns4P plays a role in actin
      reorganization induced by a plant hormone abscisic acid (ABA) in guard cells of
      day flower (Commelina communis). ABA-induced changes in actin filaments were
      inhibited by LY294002 (LY) and wortmannin (WM), inhibitors of PtdIns3P and
      PtdIns4P synthesis. Expression of PtdIns3P- and PtdIns4P-binding domains also
      inhibited ABA-induced actin reorganization in a manner similar to LY and WM.
      These results suggest that PtdIns3P and PtdIns4P regulate actin dynamics in guard
      cells. Furthermore, we demonstrate that PtdIns3P exerts its effect on actin
      dynamics, at least in part, via generation of reactive oxygen species (ROS) in
      response to ABA.

PMID- 18088332
TI  - Dynamic morphology of plastids and stromules in angiosperm plants.
AB  - Labelling of plastids with fluorescent proteins has revealed the diversity of
      their sizes and shapes in different tissues of vascular plants. Stromules, stroma
      filled tubules comprising thin extensions of the stroma surrounded by the double
      envelope membrane, have been observed to emanate from all major types of plastid,
      though less common on chloroplasts. In some tissue types, stromules are highly
      dynamic, forming, shrinking, attaching, releasing and fragmenting. Stromule
      formation is negatively affected by treatment of tissue with cytoskeletal
      inhibitors. Plastids can be connected by stromules, through which green
      fluorescent protein (GFP) and fluorescently tagged chloroplast protein complexes
      have been observed to flow. Within the highly viscous stroma, proteins traffic by
      diffusion as well as by an active process of directional travel, whose mechanism
      is unknown. In addition to exchanging materials between plastids, stromules may
      also serve to increase the surface area of the envelope for import and export,
      reduce diffusion distance between plastids and other organelles for exchange of
      materials, and anchor the plastid onto attachment points for proper positioning
      with the plant cell. Future studies should reveal how these functions may affect
      plants in adapting to the challenges of a changing environment.

PMID- 18088333
TI  - Characterization of growth-phase-specific responses to cold in Arabidopsis
      thaliana suspension-cultured cells.
AB  - To understand complex responses of plant cells to low temperatures, suspension
      cultured cells of Arabidopsis thaliana (line T87) were characterized during cold
      treatment. Freezing tolerance of cells collected at the lag or log phase was
      quite different: an increase in freezing tolerance during cold treatment was only
      detectable with cells at the lag phase. Although there were little differences in
      the osmolality of cells at the two growth phases, sugar content increased during
      cold treatment only in lag phase cells. Abscisic acid (ABA) content was greater
      at the lag phase than at the log phase throughout the cold treatment, and
      increased only in lag phase cells. Interestingly, ABA treatment resulted in an
      increase in freezing tolerance only in lag phase cells. Expression of cold
      responsive genes such as DREB1A/CBF3, COR15a and RD29A occurred in cells at the
      two growth phases; however, the extent of the induction of COR15a and RD29A was
      somewhat greater in cells at the lag phase than at the log phase. Microarray
      analysis revealed that cold-regulated genes (COR genes) were categorized into
      three groups: up- or down-regulated consistently during cold treatment,
      transiently after 1 d and later after 2 d of cold treatment. Among genes that
      were up-regulated throughout or transiently after 1 d of cold treatment only in
      lag phase cells, functions in upstream of signal transduction such as kinase and
      transcription factor were often deduced. These results collectively suggest that
      these genes seem to be associated with induction of freezing tolerance by cold
      treatment in cells at the lag phase.

PMID- 18088334
TI  - The role of cytokinins in responses to water deficit in tobacco plants over
      expressing trans-zeatin O-glucosyltransferase gene under 35S or SAG12 promoters.
AB  - The impact of water deficit progression on cytokinin (CK), auxin and abscisic
      acid (ABA) levels was followed in upper, middle and lower leaves and roots of
      Nicotiana tabacum L. cv. Wisconsin 38 plants [wild type (WT)]. ABA content was
      strongly increased during drought stress, especially in upper leaves. In plants
      with a uniformly elevated total CK content, expressing constitutively the trans
      zeatin O-glucosyltransferase gene (35S::ZOG1), a delay in the increase of ABA was
      observed; later on, ABA levels were comparable with those of WT. As drought
      progressed, the bioactive CK content in leaves gradually decreased, being
      maintained longer in the upper leaves of all tested genotypes. Under severe
      stress (11 d dehydration), a large stimulation of cytokinin oxidase/dehydrogenase
      (CKX) activity was monitored in lower leaves, which correlated well with the
      decrease in bioactive CK levels. This suggests that a gradient of bioactive CKs
      in favour of upper leaves is established during drought stress, which might be
      beneficial for the preferential protection of these leaves. During drought,
      significant accumulation of CKs occurred in roots, partially because of decreased
      CKX activity. Simultaneously, auxin increased in roots and lower leaves. This
      indicates that both CKs and auxin play a role in root response to severe drought,
      which involves the stimulation of primary root growth and branching inhibition.

PMID- 18088335
TI  - Safety and efficiency conflicts in hydraulic architecture: scaling from tissues
      to trees.
AB  - Tree hydraulic architecture exhibits patterns that propagate from tissue to tree
      scales. A challenge is to make sense of these patterns in terms of trade-offs and
      adaptations. The universal trend for conduits per area to decrease with
      increasing conduit diameter below the theoretical packing limit may reflect the
      compromise between maximizing the area for conduction versus mechanical support
      and storage. Variation in conduit diameter may have two complementary influences:
      one being compromises between efficiency and safety and the other being that
      conduit tapering within a tree maximizes conductance per growth investment. Area
      preserving branching may be a mechanical constraint, preventing otherwise more
      efficient top-heavy trees. In combination, these trends beget another: trees have
      more, narrower conduits moving from trunks to terminal branches. This pattern:
      (1) increases the efficiency of tree water conduction; (2) minimizes (but does
      not eliminate) any hydraulic limitation on the productivity or tissue growth with
      tree height; and (3) is consistent with the scaling of tree conductance and sap
      flow with size. We find no hydraulic reason why tree height should scale with a
      basal diameter to the two-thirds power as recently claimed; it is probably
      another mechanical constraint as originally proposed. The buffering effect of
      capacitance on the magnitude of transpiration-induced xylem tension appears to be
      coupled to cavitation resistance, possibly alleviating safety versus efficiency
      trade-offs.

PMID- 18088336
TI  - Expression differences for genes involved in lignin, glutathione and sulphate
      metabolism in response to cadmium in Arabidopsis thaliana and the related Zn/Cd
      hyperaccumulator Thlaspi caerulescens.
AB  - Cadmium (Cd) is a widespread, naturally occurring element present in soil, rock,
      water, plants and animals. Cd is a non-essential element for plants and is toxic
      at higher concentrations. Transcript profiles of roots of Arabidopsis thaliana
      (Arabidopsis) and Thlaspi caerulescens plants exposed to Cd and zinc (Zn) are
      examined, with the main aim to determine the differences in gene expression
      between the Cd-tolerant Zn-hyperaccumulator T. caerulescens and the Cd-sensitive
      non-accumulator Arabidopsis. This comparative transcriptional analysis emphasized
      the role of genes involved in lignin, glutathione and sulphate metabolism.
      Furthermore the transcription factors MYB72 and bHLH100 were studied for their
      involvement in metal homeostasis, as they showed an altered expression after
      exposure to Cd. The Arabidopsis myb72 knockout mutant was more sensitive to
      excess Zn or iron (Fe) deficiency than wild type, while Arabidopsis transformants
      overexpressing bHLH100 showed increased tolerance to high Zn and nickel (Ni)
      compared to wild-type plants, confirming their role in metal homeostasis in
      Arabidopsis.

PMID- 18088337
TI  - Multilevel genomic analysis of the response of transcripts, enzyme activities and
      metabolites in Arabidopsis rosettes to a progressive decrease of temperature in
      the non-freezing range.
AB  - This paper characterizes the transcriptional and metabolic response of a chilling
      tolerant species to an increasingly large decrease of the temperature.
      Arabidopsis Col-0 was grown at 20 degrees C and transferred to 17, 14, 12, 10 or
      8 degrees C for 6 and 78 h, before harvesting the rosette and profiling >22 000
      transcripts, >20 enzyme activities and >80 metabolites. Most parameters showed a
      qualitatively similar response across the entire temperature range, with the
      amplitude increasing as the temperature decreased. Transcripts typically showed
      large changes after 6 h, which were often damped by 78 h. Genes were induced for
      sucrose, proline, raffinose, tocopherol and polyamine synthesis, phenylpropanoid
      and flavonoid metabolism, fermentation, non-phosphorylating mitochondrial
      electron transport, RNA processing, and protein synthesis, targeting and folding.
      Genes were repressed for carbonic anhydrases, vacuolar invertase, and ethylene
      and jasmonic acid signalling. While some enzyme activities and metabolites
      changed rapidly, most changed slowly. After 6 h, there was an accumulation of
      phosphorylated intermediates, a shift of partitioning towards sucrose, and a
      perturbation of glycine decarboxylation and nitrogen metabolism. By 78 h, there
      was an increase of the overall protein content and many enzyme activities, a
      general increase of carbohydrates, organic and amino acids, and an increase of
      many stress-responsive metabolites including raffinose, proline, tocopherol and
      polyamines. When the responses of transcripts and metabolism were compared, there
      was little agreement after 6 h, but considerable agreement after 78 h. Comparison
      with the published studies indicated that much, but not all, of the response was
      orchestrated by the CBF programme. Overall, our results showed that transcription
      and metabolism responded in a continuous manner across a wide range of
      temperatures. The general increase of enzyme activities and metabolites
      emphasized the positive and compensatory nature of this response.

PMID- 18088338
TI  - Can blood flow assays help to identify clinically relevant differences in von
      Willebrand factor functionality in von Willebrand disease types 1-3?

PMID- 18088339
TI  - Matrix metalloproteinases in platelet function: coming of age.

PMID- 18088340
TI  - Heparin-induced thrombocytopenia in patients requiring prolonged intensive care
      unit treatment after cardiopulmonary bypass.
AB  - BACKGROUND: The diagnosis of heparin-induced thrombocytopenia (HIT) is
      problematic in postcardiac surgery (CS) intensive care unit (ICU) patients, as
      there are multiple potential explanations for thrombocytopenia and the presence
      of anti-platelet factor 4/heparin antibodies is not highly specific for HIT. Two
      platelet count profiles for HIT - a 40% or greater fall in platelet count
      beginning on or after day 5 (pattern 1) and persisting thrombocytopenia (< 100 x
      10(9) L(-1)) beyond day 7 (pattern 2) - have been described in post-CS patients.
      METHODS AND RESULTS: We examined the platelet count profiles of 329 consecutive
      post-CS patients who required ICU treatment beyond 7 days. Although 70 patients
      (21.3%) developed thrombocytopenia (57.1% pattern 1, 42.9% pattern 2), the
      overall incidence of HIT was only 1.8% [6/329; 95% confidence interval (95% CI)
      0.7-3.9%] in these ICU patients, with more HIT patients showing a pattern 2 than
      a pattern 1 platelet count decrease (four vs. two patients). Notably, pattern 2
      patients with HIT also showed a new proportional fall of > 30% in platelet count
      between postoperative days 5 and 10. Among the remaining 2242 post-CS patients
      without a prolonged ICU stay, only three (0.1%; 95% CI 0.03-0.4%) developed
      symptomatic HIT (OR 0.07; 95% CI 0.01-0.3; P = 0.0002 vs. ICU patients), all
      presenting with pattern 1. CONCLUSIONS: Among post-CS ICU patients, a
      postoperative platelet count fall between days 5 and 10 increases diagnostic
      specificity for HIT, irrespective of whether this platelet count fall occurs
      after postoperative platelet count recovery (pattern 1) or is superimposed upon
      persisting postoperative thrombocytopenia (pattern 2). A prospective study is
      required in order to validate the findings of this retrospective analysis.

PMID- 18088341
TI  - Enhancement of the enzymatic activity of activated coagulation factor IX by anti
      factor IX antibodies.
AB  - BACKGROUND: Factor VIIIa (FVIIIa) binds to activated FIX and enhances the
      activation of FX by several orders of magnitude. Deficiency of FVIII causes the
      bleeding disorder hemophilia A and is treated by i.v. infusion of FVIII
      concentrates. OBJECTIVES: To explore whether or not FVIII activity can be
      supplied by alternative molecules, e.g. molecules with FIXa-binding activity.
      METHODS: Conventional hybdridoma technology was used to discover antibodies
      exhibiting FVIII-like activity. RESULTS: We identified a series of antibodies
      specific for human FIX that mimicked the stimulatory effect of FVIIIa on FIXa.
      Upon binding to human FIXa, these antibodies enhanced the protease activity of
      FIXa towards its natural substrate FX about tenfold. A similar enhancement was
      also achieved with 5 pm FVIIIa (i.e. 16 mU mL(-1) or 1.6% activated FVIII).
      Procoagulant activity of these anti-FIXa antibodies was observed in model systems
      containing purified proteins as well as in plasma. CONCLUSION: Our findings show
      that FVIII can, at least partially, be replaced by an unrelated molecule.
      Procoagulant antibodies might potentially aid the development of an FVIII
      substitute for hemophilia A treatment.

PMID- 18088342
TI  - Platelets modulate atherogenesis and progression of atherosclerotic plaques via
      interaction with progenitor and dendritic cells.
AB  - Platelets not only play a role in the late complications of atherosclerosis, but
      are also essential in its initiation, interacting with endothelial cells and
      leukocytes. Platelet adhesion to injured or atherosclerotic vessels is critical
      for the initiation of atherosclerotic lesion formation in vivo. Increasing
      evidence has recently highlighted the role of progenitor cells in inflammation,
      atherogenesis, and atheroprogression. Recruitment of progenitor and dendritic
      cells to sites of vascular injury is poorly understood so far. Both human
      progenitor and dendritic cells significantly adhere to platelets, indicating that
      platelets adherent to collagen or to endothelial cells can serve as a bridging
      mechanism directing circulating progenitor and dendritic cells to sites of
      impaired vasculature. Moreover, platelets regulate differentiation of progenitor
      cells to endothelial cells or macrophages and foam cells and modulate essential
      functions of dendritic cells, including their activation, differentiation and
      apoptosis in vitro. This review describes recent findings on platelet interaction
      with progenitor cells or dendritic cells and discusses potential consequences of
      this interaction in atherosclerosis.

PMID- 18088343
TI  - Reciprocal regulation of platelet responses to P2Y and thromboxane receptor
      activation.
AB  - BACKGROUND: Thromboxane A(2) and ADP are two major platelet agonists that
      stimulate two sets of G protein-coupled receptors to activate platelets. Although
      aggregation responses to ADP and thromboxane desensitize, there are no reports
      currently addressing whether activation by one agonist may heterologously
      desensitize responses to the other. OBJECTIVES: To demonstrate whether responses
      to ADP or U46619 may be modulated by prior treatment of platelets with the
      alternate agonist, revealing a level of cross-desensitization between receptor
      systems. RESULTS: Here we show that pretreatment of platelets with either agonist
      substantially desensitizes aggregation responses to the other agonist. Calcium
      responses to thromboxane receptor activation are desensitized by preactivation of
      P2Y(1) but not P2Y(12) receptors. This heterologous desensitization is mediated
      by a protein kinase C (PKC)-independent mechanism. Reciprocally, calcium
      responses to ADP are desensitized by pretreatment of platelets with the
      thromboxane analogue, U46619, and P2Y(12)-mediated inhibition of adenylate
      cyclase is also desensitized by pretreatment with U46619. In this direction,
      desensitization is comprised of two components, a true heterologous component
      that is PKC-independent, and a homologous component that is mediated through
      stimulated release of dense granule ADP. CONCLUSIONS: This study reveals cross
      desensitization between ADP and thromboxane receptor signaling in human
      platelets. Cross-desensitization is mediated by protein kinases, involving PKC
      dependent and independent pathways, and indicates that alterations in the
      activation state of one receptor may have effects upon the sensitivity of the
      other receptor system.

PMID- 18088344
TI  - Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis.

PMID- 18088345
TI  - Recollections on thrombin generation.
AB  - Against an autobiographic background, a historical sketch is given of the
      development of the technique of thrombin generation, from subsampling to duly
      calibrated continuous measurement with fluorogenic substrates. Its application to
      various problems in the pathophysiology of hemostasis and thrombosis is
      discussed.

PMID- 18088346
TI  - Quality assurance for oral anticoagulation self management: a cluster randomized
      trial.
AB  - BACKGROUND AND AIMS: External quality assessment (EQA) should be an inherent
      component of patient self management (PSM) of oral anticoagulation. The aim of
      this study was to evaluate methods of EQA for patients within a cluster
      randomized trial. METHOD: After development of methods, general practises were
      randomly allocated to a formal EQA scheme of patients performing the test
      independently at home or at their practise with supervision. The supervised group
      of practises was further sub divided to test two other EQA methods: (i) venous
      sample compared with patients' point of care (POC) device; and (ii) patients POC
      compared with reference POC. Primary trial outcome measure was reliability of
      results from the formal scheme taking into account adherence and test errors.
      RESULTS: Proportion of EQA scheme tests in range was 633/836 (75.7%). Proportion
      in range was significantly higher in group performing independently compared with
      supervised group, 80.1% vs. 71.5% respectively, P = 0.02. Sixty-six percent of
      tests were in range with venous compared with patients POC, and 88% in patients
      POC compared with reference POC. CONCLUSION: Patients are able to undertake a
      formal EQA scheme and perform more reliably at home independently. There are
      satisfactory alternatives if a formal scheme is not acceptable.

PMID- 18088347
TI  - Prediction of hemorrhagic and thrombotic events in patients with mechanical heart
      valve prostheses treated with oral anticoagulants.
AB  - BACKGROUND: Variability in the intensity of anticoagulant therapy is considered a
      risk factor for complications, but it is unclear how best to quantify
      variability. OBJECTIVE: We evaluated the association of three methods to measure
      variability with complications of oral anticoagulant therapy. METHODS: We
      conducted a nested case-control study within a cohort of patients with prosthetic
      heart valves. 210 patients with a first hemorrhagic or thrombotic event during
      follow-up were selected with two controls per case, matched on age and sex. We
      calculated the time spent at an International Normalized Ratio below, above, and
      between 2.5 and 4.0, and the variance growth rate according to three different
      methods (A, B1, B2); method A combines variability and time in range, and methods
      B1 and B2 purely look at variability. RESULTS: Odds ratios of the variance growth
      rates for thrombotic events for patients in the second and third tertiles varied
      between 2 and 3, with the highest odds ratio for complications for the method
      that purely looked at variability. For hemorrhagic complications, the highest
      odds ratios were found for method A, which also incorporated time in range, with
      odds ratios of 2.6 (95% CI: 1.3-5.1) and 3.1 (95% CI: 1.6-6.0) for the second and
      third tertiles as compared to the first. The combination of time spent out of
      range with the highest tertile of variability increased the risk 2.6-fold (95%
      CI: 1.6-4.2) as compared to subjects with stable anticoagulation within the
      target range. CONCLUSION: Unstable anticoagulation was associated with
      hemorrhagic and thrombotic complications. Method A was best associated with
      complications, but methods B1 and B2, in combination with time spent in range,
      were equally well associated. As we prefer to disentangle variability and
      intensity of anticoagulation, we propose to use methods B1 or B2 to reflect pure
      variability of oral anticoagulant therapy.

PMID- 18088348
TI  - Tissue-specific hemostasis: role of tissue factor.

PMID- 18088349
TI  - Partial factor IXa inhibition with TTP889 for prevention of venous
      thromboembolism: an exploratory study.
AB  - BACKGROUND: Inhibitors of factor (F) IXa show potent antithrombotic activity with
      a low risk of bleeding in preclinical models. We investigated the anticoagulant
      potential of oral TTP889, a small molecule that inhibits up to 90% of FIXa
      activity at therapeutic doses, using a clinical model of extended prophylaxis in
      hip fracture surgery (HFS). METHODS: In this multicenter, randomized, double
      blind study, 261 patients received oral TTP889 (300 mg once daily) or placebo
      starting 6-10 days after HFS, and standard thromboprophylaxis for 5-9 days.
      Treatment was continued for 3 weeks and all patients then underwent mandatory
      bilateral venography. The primary efficacy outcome was venous thromboembolism
      (VTE; venographic or symptomatic deep vein thrombosis or pulmonary embolism)
      during treatment, and it was evaluated centrally by an independent adjudication
      panel. The main safety outcome was bleeding (major, clinically relevant non
      major, and minor events). RESULTS: Two hundred and twelve patients with an
      evaluable venogram were included in the efficacy analysis. The primary efficacy
      outcome occurred in 32.1% (35/109) of patients who had been allocated TTP889, and
      28.2% (29/103) of patients on placebo (P = 0.58). There were no major bleeding
      events, and only two clinically relevant non-major bleeding events with TTP889.
      CONCLUSION: Partial FIXa inhibition with TTP889 300 mg daily was not effective
      for extended prevention of VTE after standard prophylaxis for up to 9 days.
      Coupled with the low incidence of bleeding episodes, this suggests a lack of
      antithrombotic potential. Further investigation of TTP889 in different clinical
      settings is needed. (Clinical trial registration information URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00119457).

PMID- 18088350
TI  - MMP-2 regulates human platelet activation by interacting with integrin
      alphaIIbbeta3.
AB  - BACKGROUND: Human platelets contain matrix metalloproteinases (MMPs) that are
      secreted during platelet activation. Platelet MMPs have been implicated in the
      regulation of cellular activation and aggregation. Although the proaggregatory
      effect of MMP-2 has been demonstrated, the functional mechanism is not clearly
      understood. OBJECTIVES: This work was carried out in order to elucidate the
      biochemical mechanism of MMP-2-associated platelet activation and aggregation.
      METHODS: MMP-2 binding to the platelet surface was analyzed by flow cytometry.
      The cell surface target of MMP-2 was identified in thrombin receptor-activating
      peptide-stimulated platelets by immunoprecipitation, Western blotting and
      fluorescence microscopy. A recombinant hemopexin-like domain was used to
      characterize the nature of MMP-2 binding to the platelet surface. The functional
      significance of MMP-2 in platelet activation was investigated by quantitative
      measurements of the activation markers P-selectin (CD62P) and active
      alpha(IIb)beta(3). The role of MMP-2 in platelet aggregation was analyzed with an
      aggregometer. RESULTS: ProMMP-2 binds to integrin alpha(IIb)beta(3) in stimulated
      platelets in which proMMP-2 is converted into MMP-2. Fibrinogen was able to
      replace the alpha(IIb)beta(3)-bound MMP-2. The molecular interaction of MMP-2 and
      integrin alpha(IIb)beta(3) was abrogated by the recombinant human hemopexin-like
      domain of MMP-2, leading to reduced cell surface expression of activation markers
      CD62P and active alpha(IIb)beta(3), and resulting in suppressed platelet
      aggregation. CONCLUSION: This work clearly demonstrates that platelet activation
      and aggregation is regulated by MMP-2 that specifically interacts with integrin
      alpha(IIb)beta(3). The C-terminal hemopexin-like domain of MMP-2 is an essential
      element for binding to alpha(IIb)beta(3).

PMID- 18088351
TI  - Antithrombin inhibits lipopolysaccharide-induced tumor necrosis factor-alpha
      production by monocytes in vitro through inhibition of Egr-1 expression.
AB  - BACKGROUND: Antithrombin (AT) improves the outcome of septic patients with
      intravascular coagulation. However, the mechanisms underlying the therapeutic
      benefits of AT are not fully understood. Tumor necrosis factor-alpha (TNF-alpha)
      plays a critical role in the development of organ failure and intravascular
      coagulation in sepsis. AIM: This study aimed to elucidate a molecular mechanism
      by which AT inhibits TNF-alpha production. METHODS: Human peripheral monocyte was
      stimulated by lipopolysaccharide (LPS) and TNF-alpha concentration in media was
      measured. Levels of phosphorylation of extracellular signal-regulated protein
      kinases (ERK) 1/2 and early growth response factor-1 (Egr-1) were estimated by
      western blotting or by electrophoretic mobility shift assay. RESULTS:
      Antithrombin (3 U mL(-1)) inhibited TNF-alpha production by monocytes stimulated
      with LPS. Conversely, chemically modified AT that lacks affinity for heparin did
      not. AT inhibited the phosphorylation of ERK 1/2 and decreased the expression of
      Egr-1 in LPS-stimulated monocytes. However, it did not affect the activation of
      either nuclear factor-kappaB or activator protein-1. Pretreatment with KT5720, a
      protein kinase A inhibitor, reversed the inhibitory effect of AT on the LPS
      induced phosphorylation of ERK1/2. Although 2 U mL(-1) AT slightly inhibited TNF
      alpha production by LPS-stimulated monocytes, it significantly inhibited TNF
      alpha production in the presence of a low concentration of beraprost, a stable
      derivative of prostacyclin. CONCLUSIONS: These observations suggest that AT might
      inhibit LPS-induced production of TNF-alpha by inhibiting the increase in Egr-1
      expression in monocytes via interaction with heparin-like substances expressed on
      the cell surface.

PMID- 18088352
TI  - Basic fibroblast growth factor-induced protection from light damage in the mouse
      retina in vivo.
AB  - Basic fibroblast growth factor (bFGF) has proven neuroprotective efficacy in the
      rodent retina against a diverse array of injurious stimuli. However, there is no
      consensus to date as to the molecular mechanisms underlying this neuroprotection.
      The study presented herein demonstrates increased expression of endogenous bFGF
      in the albino mouse retina in response to acute exposure to sublethal levels of
      light stress. The increased expression correlates with significant photoreceptor
      protection from light damage. The neuroprotection is likely to be mediated by
      bFGF as we demonstrate that a shorter exposure to bright light stress that does
      not up-regulate bFGF fails to protect photoreceptors from light damage.
      Furthermore, intravitreal bFGF injection into the retina of mice 3 h prior to
      light damage affords almost complete photoreceptor protection from light-induced
      degeneration. In addition, injected bFGF induces the activation of protein kinase
      B and extracellular signal-regulated kinase 1/2 signalling which correlate
      directly with the pathways we find to be activated in response to light stress
      and up-regulated bFGF. Moreover, we demonstrate that both bright light pre
      conditioning and intravitreal bFGF injection result in dramatic increases in
      levels of inactive glycogen synthase kinase 3beta and cyclic AMP response element
      binding protein phosphorylation indicating a potential mechanism by which bFGF
      promotes survival of photoreceptors in vivo.

PMID- 18088353
TI  - Y1 receptors are critical for the proliferation of adult mouse precursor cells in
      the olfactory neuroepithelium.
AB  - While the regenerative capacity of the olfactory neuroepithelium has been well
      studied less is known about the molecular events controlling precursor cell
      activity. Neuropeptide Y (NPY) is expressed at high levels in the olfactory
      system, and NPY has been shown to play a role in neuroregeneration of the brain.
      In this study, we show that the numbers of olfactory neurospheres derived from
      NPY, NPY/peptide YY, and Y1 receptor knockout mice are decreased compared with
      wild type (WT) controls. Furthermore, flow cytometric analysis of isolated
      horizontal basal cells, globose basal cells, and glandular cells showed that only
      glandular cells derived from WT mice, but not from NPY and Y1 receptor knockout
      mice, formed secondary neurospheres suggesting a critical role for NPY signaling
      in this process. Interestingly, olfactory function tests revealed that olfaction
      in Y1 knockout mice is impaired compared with those of WT mice, probably because
      of the reduced number of olfactory neurons formed. Together these results
      indicate that NPY and the Y1 receptor are required for the normal proliferation
      of adult olfactory precursors and olfactory function.

PMID- 18088354
TI  - NMDA receptor-mediated excitotoxic neuronal apoptosis in vitro and in vivo occurs
      in an ER stress and PUMA independent manner.
AB  - Disruption of endoplasmic reticulum (ER) Ca2+ homeostasis and ER dysfunction have
      been suggested to contribute to excitotoxic and ischaemic neuronal injury.
      Previously, we have characterized the neural transcriptome following ER stress
      and identified the BH3-only protein, p53 up-regulated mediator of apoptosis
      (PUMA), as a central mediator of ER stress toxicity. In this study, we
      investigated the effects of excitotoxic injury on ER Ca2+ levels and induction of
      ER stress responses in models of glutamate- and NMDA-induced excitotoxic
      apoptosis. While exposure to the ER stressor tunicamycin induced an ER stress
      response in cerebellar granule neurons, transcriptional activation of targets of
      the ER stress response, including PUMA, were absent following glutamate-induced
      apoptosis. Confocal imaging revealed no long-term changes in the ER Ca2+ level in
      response to glutamate. Murine cortical neurons and organotypic hippocampal slice
      cultures from PUMA+/+ and PUMA-/- animals provided no evidence of ER stress and
      did not differ in their sensitivity to NMDA. Finally, NMDA-induced excitotoxic
      apoptosis in vivo was not associated with ER stress, nor did deficiency in PUMA
      alleviate the injury induced. Our data suggest that NMDA receptor-mediated
      excitotoxic apoptosis occurs in vitro and in vivo in an ER stress and PUMA
      independent manner.

PMID- 18088355
TI  - Serum- and glucocorticoid-inducible kinase 1 enhances zif268 expression through
      the mediation of SRF and CREB1 associated with spatial memory formation.
AB  - Serum- and glucocorticoid-inducible kinase 1 (SGK1) has been shown to play an
      important role in spatial memory formation, but the molecular mechanism
      underlying this effect of SGK1 was not known. zif268 is an immediate early gene
      that is induced by water maze learning. To investigate the role of SGK1 in the
      regulation of zif268 expression, the dominant negative mutant of SGK1, SGK1
      S422A, was infused to the hippocampal CA1 area of rats, and was found to decrease
      significantly the mRNA level of zif268 in both naive animals and trained animals.
      SGK1 was also found to phosphorylate serum response factor (SRF) at Ser73, Ser75,
      and Ser99, and phosphorylate CREB1 at Ser133. Inhibition of SGK1 phosphorylation
      sites on SRF and CREB1 with alanine substitution significantly diminished SGK1
      enhanced zif268 expression in the promoter-luciferase assay. SGK1 also
      phosphorylates Elk-1 and SGK1 phosphorylation of Elk-1 decreased the
      transcriptional activity of Elk-1. But SGK1 phosphorylation of Elk-1 did not
      affect SGK1-enhanced zif268 expression. Moreover, the phosphorylation of SGK1 was
      increased in rat CA1 area after water maze learning, accompanied by increased
      phosphorylation of SRF at Ser99 and increased phosphorylation of CREB1 at Ser133.
      All these effects were antagonized by SGK1 S422A transfection. These results
      together suggest that SGK1 enhances zif268 expression through the mediation of
      SRF and CREB1, and these signaling pathways are associated with spatial memory
      formation in rats.

PMID- 18088356
TI  - Metabolic changes detected by proton magnetic resonance spectroscopy in vivo and
      in vitro in a murin model of Parkinson's disease, the MPTP-intoxicated mouse.
AB  - Parkinson's disease is a neurodegenerative disorder characterized by the
      progressive loss of the dopaminergic neurons in the substantia nigra pars
      compacta, which project to the striatum. The aim of this study was to analyze in
      vivo and in vitro consequences of dopamine depletion on amount of metabolites in
      a mouse model of Parkinson's disease using proton (1)H magnetic resonance
      spectroscopy (MRS). The study was performed on control mice (n = 7) and MPTP
      intoxicated mice (n = 7). All the experiments were performed at 9.4 T. For in
      vivo MRS acquisitions, mice were anesthetized and carefully placed on an animal
      handling system with the head centered in birdcage coil used for both excitation
      and signal reception. Spectra were acquired in a voxel (8 microL) centered in the
      striatum, applying a point-resolved spectroscopy sequence (TR = 4000 ms, TE = 8.8
      ms). After in vivo MRS acquisitions, mice were killed; successful lesion verified
      by tyrosine hydroxylase immunolabeling on the substantia nigra pars compacta and
      in vitro MRS acquisitions performed on perchloric extracts of anterior part of
      mice brains. In vitro spectra were acquired using a standard one-pulse
      experiment. The absolute concentrations of metabolites were determined using
      jmrui (Lyon, France) from (1)H spectra obtained in vivo on striatum and in vitro
      on perchloric extracts. Glutamate (Glu), glutamine (Gln), and GABA concentrations
      obtained in vivo were significantly increased in striatum of MPTP-lesioned mice
      (Glu: 15.5 +/- 2.5 vs. 12.9 +/- 1.0 mmol/L, p < 0.05; Gln: 2.3 +/- 0.9 vs. 1.8 +/
      0.6 mmol/L, p < 0.05; GABA: 2.3 +/- 0.9 vs. 1.3 +/- 0.6 mmol/L, p < 0.05). The
      in vitro results confirmed these results, Glu (10.9 +/- 2.5 vs. 7.9 +/- 1.7
      micromol/g, p < 0.05), Gln (6.8 +/- 2.9 vs. 4.3 +/- 1.0 micromol/g, p < 0.05),
      and GABA (2.9 +/- 0.9 vs. 1.5 +/- 0.4 micromol/g, p < 0.01). The present study
      strongly supports a hyperactivity of the glutamatergic cortico-striatal pathway
      hypothesis after dopaminergic denervation in association with an increase of
      striatal GABA levels. It further shows an increased of striatal Gln
      concentrations, perhaps as a strategy to protect neurons from Glu excitotoxic
      injury after striatal dopamine depletion.

PMID- 18088357
TI  - Expression and comparative characterization of Gq-coupled invertebrate visual
      pigments and melanopsin.
AB  - A non-visual pigment melanopsin, which is localized in photosensitive retinal
      ganglion cells and is involved in the circadian photoentrainment and pupillary
      responses in mammals, is phylogenetically close to the visual pigments of
      invertebrates, such as insects and cephalopods. Recent studies suggested that
      melanopsin is a bistable pigment and drives a Gq-mediated signal transduction
      cascade, like the invertebrate visual pigments. Because detailed
      electrophysiological properties are somewhat different between the visual cells
      and the photosensitive ganglion cells, we here expressed and purified the
      invertebrate visual pigment and melanopsin to comparatively investigate their Gq
      activation abilities. We successfully expressed and purified UV and blue light
      sensitive visual pigments of the honeybee as well as the amphioxus melanopsin.
      Although the purified UV-sensitive pigment and the melanopsin lost their bistable
      nature during purification, reconstitution of the pigments in lipid vesicles
      resulted in return of the bistable nature. The light-dependent Gq-activation
      abilities among these reconstituted pigments are similar, suggesting that the
      electrophysiological differences do not depend on the Gq-activation step but
      rather on the other signal transduction steps and/or on cell properties. Our
      findings are also important in that this is the first report describes a
      heterologous large-scale expression of the Gq-coupled invertebrate visual
      pigments in cultured cells.

PMID- 18088358
TI  - Nesfatin-1 influences the excitability of paraventricular nucleus neurones.
AB  - Nesfatin-1 is a newly-discovered satiety peptide found in several nuclei of the
      hypothalamus, including the paraventricular nucleus. To begin to understand the
      physiological mechanisms underlying these satiety-inducing actions, we examined
      the effects of nesfatin-1 on the excitability of neurones in the paraventricular
      nucleus. Whole-cell current-clamp recordings from rat paraventricular nucleus
      neurones showed nesfatin-1 to have either hyperpolarizing or depolarising effects
      on the majority of neurones tested. Both types of response were observed in
      neurones irrespective of classification based on electrophysiological fingerprint
      (magnocellular, neuroendocrine or pre-autonomic) or molecular phenotype
      (vasopressin, oxytocin, corticotrophin-releasing hormone, thyrotrophin-releasing
      hormone or vesicular glutamate transporter), determined using single cell reverse
      transcription-polymerase chain reaction. Consequently, we provide the first
      evidence that this peptide, which is produced in the paraventricular nucleus, has
      effects on the membrane potential of a large proportion of different
      subpopulations of neurones located in this nucleus, and therefore identify
      nesfatin-1 as a potentially important regulator of paraventricular nucleus
      output.

PMID- 18088359
TI  - Differential kinetics of oxytocin and vasopressin heteronuclear RNA expression in
      the rat supraoptic nucleus in response to chronic salt loading in vivo.
AB  - Previous studies have shown that the secretion of oxytocin and vasopressin from
      the posterior pituitary always accompanies systemic hyperosmotic stimuli in rats,
      and that oxytocin and vasopressin mRNAs consistently increase in response to
      prolonged hyperosmotic stimuli. Hence, it has been widely interpreted that
      oxytocin and vasopressin secretion and gene expression are closely coupled. In
      the present study, we used both vasopressin and oxytocin intron- specific probes
      to measure vasopressin and oxytocin heteronuclear RNA (hnRNA) levels,
      respectively, by in situ hybridisation in the rat supraoptic nucleus (SON) in
      conjunction with radioimmunoassays of vasopressin and oxytocin peptide levels in
      plasma and in the posterior pituitary in normally hydrated rats and after 1-5
      days of salt loading. Increased oxytocin secretion in response to hyperosmotic
      stimuli exceeded vasopressin secretion at every time point studied. Vasopressin
      hnRNA in the SON increased to near maximal levels within minutes after the
      hyperosmotic stimulus, and was maintained throughout all 5 days of salt loading.
      By contrast, oxytocin hnRNA did not significantly change from control levels
      until approximately 2 days after hyperosmotic stimulation, and was not maximal
      until 3 days. In summary, increases in oxytocin gene transcription in response to
      osmotic stimuli are dramatically delayed compared to increases in vasopressin
      gene transcription under the same conditions. These data indicate that oxytocin
      gene transcription is not as closely correlated with pituitary peptide secretion
      as is vasopressin gene transcription, and suggests that there is a fundamental
      difference in excitation-secretion-transcription coupling mechanisms that
      regulate these two closely related genes in the rat magnocellular neurones in the
      SON.

PMID- 18088360
TI  - Beta-melanocyte-stimulating hormone potently reduces appetite via the
      hypothalamus in chicks.
AB  - The melanocortin system together with other appetite-related systems plays a
      significant role in appetite regulation. The appetite-related effects of one such
      melanocortin, beta-melanocyte-stimulating hormone (MSH), are well documented in
      rodents; however, its effects in the avian class are not thoroughly understood.
      Thus, we designed a study to determine the effects of i.c.v. beta-MSH injection
      on food and water intake, plasma corticosterone concentration, ingestive and non
      ingestive behaviours, and hypothalamic neuronal activation using Cobb-500 chicks.
      Chicks responded to beta-MSH-treatment with a reduction in food and water intake;
      however when water intake was measured independently of food intake, it was not
      affected. beta-MSH-treated chicks also had increased plasma corticosterone
      concentrations and increased c-Fos reactivity in the periventricular,
      paraventricular and infundibular nuclei, and the ventromedial hypothalamus;
      however, the lateral hypothalamus was not affected. The effect on food intake is
      primary because behaviours that may be competitive with food intake were not
      increased in beta-MSH-treated chicks. Based on these results, we conclude that
      beta-MSH causes anorexigenic effects that are likely primarily mediated via
      stimulation of satiety-related hypothalamic nuclei in broiler-type chicks.

PMID- 18088361
TI  - Feeding behaviour in galanin knockout mice supports a role of galanin in fat
      intake and preference.
AB  - It has been widely suggested that saturated fat consumption has fuelled the
      current obesity epidemic. Macronutrient choices appear to be important not only
      as potential factors influencing obesity, but also independently as risk factors
      for diabetes, cardiovascular disease and cancer. The neuropeptide galanin has
      previously been implicated in the regulation of fat intake, although its precise
      role has been contested. The present study investigated mice with targeted
      knockout of the galanin gene (GKO). We demonstrate that, when only a high fat
      diet (HFD) was available, wild-type (WT) animals consumed significantly more
      energy than the GKO mice (89.85 +/- 4.57 kJ/day versus 76.84 +/- 3.55 kJ/day, P <
      0.001, n = 17 versus 15). Consistent with this, WT animals gained more body
      weight when fed the HFD than GKO animals (3.48 +/- 0.44 g versus 2.02 +/- 0.62 g,
      P < 0.001, n = 17 versus 15). In a macronutrient choice scenario, WT mice ate
      almost three-fold more fat than GKO animals (0.63 +/- 0.02 g versus 0.23 +/- 0.01
      g, P < 0.001, n = 18 versus 24). Chronic administration of galanin by mini
      osmotic pumps into the lateral ventricle of GKO animals partially reversed the
      fat avoidance phenotype. Fat intake was significantly lower in the phosphate
      buffered saline-treated GKO group compared to galanin-treated GKO animals (0.32
      +/- 0.01 g versus 0.38 +/- 0.01 g, P < 0.005, n = 17 versus 17). These data are
      compatible with the hypothesis that galanin specifically regulates fat intake,
      and implies that an antagonist to one or more of the galanin receptor subtype(s)
      may be of use in the treatment of some forms of obesity.

PMID- 18088362
TI  - Voltage-dependent calcium channels in ventromedial hypothalamic neurones of
      postnatal rats: modulation by oestradiol and phenylephrine.
AB  - Oestradiol actions in the hypothalamus play an important role in reproductive
      behaviour. Oestradiol treatment in vivo induces alpha(1b)-adrenoceptor mRNA and
      increases the density of alpha(1B)-adrenoceptor binding in the hypothalamus.
      Oestradiol is also known to modulate neuronal excitability, in some cases by
      modulating calcium channels. We assessed the effects of phenylephrine, an
      alpha(1)-adrenergic agonist, on low-voltage-activated (LVA) and high-voltage
      activated (HVA) calcium channels in ventromedial hypothalamic (VMN) neurones from
      vehicle- and oestradiol-treated female rats. Whole-cell and gramicidin perforated
      patch recordings were obtained, with barium as the charge carrier. In the absence
      of phenylephrine, oestradiol treatment increased the magnitude of LVA currents
      compared to controls, but had no effect on HVA currents. Phenylephrine enhanced
      HVA currents in a significantly greater proportion of neurones from oestradiol
      treated rats (76%) than from vehicle-treated (41%) rats. The L-channel blocker
      nifedipine abolished this oestradiol effect on phenylephrine-enhanced HVA
      currents. Preincubating slices with the N-type channel blocker omega-conotoxin
      GVIA completely blocked the phenylephrine response, suggesting that the N-type
      channel is essential. Phenylephrine also stimulated LVA currents in approximately
      two-thirds of neurones in slices from both vehicle- and oestradiol-treated rats.
      Our data show that oestradiol increases LVA currents in the VMN. Oestradiol also
      amplifies alpha(1)-adrenergic signalling by increasing the proportion of neurones
      showing phenylephrine-stimulated HVA currents mediated by N- and L-type calcium
      channels. In this way, oestradiol may increase excitatory responses to arousing
      adrenergic inputs to VMN neurones governing oestradiol-dependent reproductive
      behaviour.

PMID- 18088363
TI  - Daily meal timing is not necessary for resetting the main circadian clock by
      calorie restriction.
AB  - In rodents, entrainment and/or resetting by feeding of the central circadian
      clock, the suprachiasmatic nucleus (SCN), is more efficient when food cues arise
      from a timed calorie restriction. Because timed calorie restriction is associated
      with a single meal each day at the same time, its resetting properties on the SCN
      possibly depend on a combination of meal time-giving cues and hypocaloric
      conditions per se. To exclude any effect of daily meal timing in resetting by
      calorie restriction, the present study employed a model of ultradian feeding
      schedules, divided into six meals with different durations of food access (6 x 8
      min versus 6 x 12-min meal schedule) every 4 h over the 24-h cycle. The effects
      of such an ultradian calorie restriction were evaluated on the rhythms of wheel
      running activity (WRA) and body temperature (Tb) in rats. The results indicate
      that daily/circadian rhythms of WRA and Tb were shifted by a hypocaloric feeding
      distributed in six ultradian short meals (i.e. 6 x 8-min meal schedule), showing
      both phase advances and delays. The magnitude of phase shifts was positively
      correlated with body weight loss and level of day-time behavioural activity. By
      contrast, rats fed daily with six ultradian meals long enough (i.e. 6 x 12-min
      meal schedule) to prevent body weight loss, showed only small, if any, phase
      shifts in WRA and Tb rhythms. The results obtained reveal the potency of calorie
      restriction to reset the SCN clock without synchronisation to daily meal timing,
      highlighting functional links between metabolism, calorie restriction and the
      circadian timing system.

PMID- 18088365
TI  - Mass spectral comparison of the neuropeptide complement of the stomatogastric
      ganglion and brain in the adult and embryonic lobster, Homarus americanus.
AB  - Neuropeptides in the stomatogastric ganglion (STG) and the brain of adult and
      late embryonic Homarus americanus were compared using a multi-faceted mass
      spectral strategy. Overall, 29 neuropeptides from 10 families were identified in
      the brain and/or the STG of the lobster. Many of these neuropeptides are reported
      for the first time in the embryonic lobster. Neuropeptide extraction followed by
      liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry
      enabled confident identification of 24 previously characterized peptides in the
      adult brain and 13 peptides in the embryonic brain. Two novel peptides
      (QDLDHVFLRFa and GPPSLRLRFa) were de novo sequenced. In addition, a comparison of
      adult to embryonic brains revealed the presence of an incompletely processed form
      of Cancer borealis tachykinin-related peptide 1a (CabTRP 1a, APSGFLGMRG) only in
      the embryonic brain. A comparison of adult to embryonic STGs revealed that
      QDLDHVFLRFa was present in the embryonic STG but absent in the adult STG, and
      CabTRP 1a exhibited the opposite trend. Relative quantification of neuropeptides
      in the STG revealed that three orcokinin family peptides (NFDEIDRSGFGF,
      NFDEIDRSGFGFV, and NFDEIDRSGFGFN), a B-type allatostatin (STNWSSLRSAWa), and an
      orcomyotropin-related peptide (FDAFTTGFGHS) exhibited higher signal intensities
      in the adult relative to the embryonic STG. RFamide (Arg-Phe-amide) family
      peptide (DTSTPALRLRFa), [Val(1)]SIFamide (VYRKPPFNGSIFa), and orcokinin-related
      peptide (VYGPRDIANLY) were more intense in the embryonic STG spectra than in the
      adult STG spectra. Collectively, this study expands our current knowledge of the
      H. americanus neuropeptidome and highlights some intriguing expression
      differences that occur during development.

PMID- 18088364
TI  - The newly synthesized pool of dopamine determines the severity of methamphetamine
      induced neurotoxicity.
AB  - The neurotransmitter dopamine (DA) has long been implicated as a participant in
      the neurotoxicity caused by methamphetamine (METH), yet, its mechanism of action
      in this regard is not fully understood. Treatment of mice with the tyrosine
      hydroxylase (TH) inhibitor alpha-methyl-p-tyrosine (AMPT) lowers striatal
      cytoplasmic DA content by 55% and completely protects against METH-induced damage
      to DA nerve terminals. Reserpine, by disrupting vesicle amine storage, depletes
      striatal DA by more than 95% and accentuates METH-induced neurotoxicity. l-DOPA
      reverses the protective effect of AMPT against METH and enhances neurotoxicity in
      animals with intact TH. Inhibition of MAO-A by clorgyline increases pre-synaptic
      DA content and enhances METH striatal neurotoxicity. In all conditions of altered
      pre-synaptic DA homeostasis, increases or decreases in METH neurotoxicity
      paralleled changes in striatal microglial activation. Mice treated with AMPT, l
      DOPA, or clorgyline + METH developed hyperthermia to the same extent as animals
      treated with METH alone, whereas mice treated with reserpine + METH were
      hypothermic, suggesting that the effects of alterations in cytoplasmic DA on METH
      neurotoxicity were not strictly mediated by changes in core body temperature.
      Taken together, the present data reinforce the notion that METH-induced release
      of DA from the newly synthesized pool of transmitter into the extracellular space
      plays an essential role in drug-induced striatal neurotoxicity and microglial
      activation. Subtle alterations in intracellular DA content can lead to
      significant enhancement of METH neurotoxicity. Our results also suggest that
      reactants derived from METH-induced oxidation of released DA may serve as
      neuronal signals that lead to microglial activation early in the neurotoxic
      process associated with METH.

PMID- 18088366
TI  - Cell type-specific subunit composition of G protein-gated potassium channels in
      the cerebellum.
AB  - G protein-gated inwardly rectifying potassium (GIRK/Kir3) channels regulate
      cellular excitability and neurotransmission. In this study, we used biochemical
      and morphological techniques to analyze the cellular and subcellular
      distributions of GIRK channel subunits, as well as their interactions, in the
      mouse cerebellum. We found that GIRK1, GIRK2, and GIRK3 subunits co-precipitated
      with one another in the cerebellum and that GIRK subunit ablation was correlated
      with reduced expression levels of residual subunits. Using quantitative RT-PCR
      and immunohistochemical approaches, we found that GIRK subunits exhibit
      overlapping but distinct expression patterns in various cerebellar neuron
      subtypes. GIRK1 and GIRK2 exhibited the most widespread and robust labeling in
      the cerebellum, with labeling particularly prominent in granule cells. A high
      degree of molecular diversity in the cerebellar GIRK channel repertoire is
      suggested by labeling seen in less abundant neuron populations, including
      Purkinje neurons (GIRK1/GIRK2/GIRK3), basket cells (GIRK1/GIRK3), Golgi cells
      (GIRK2/GIRK4), stellate cells (GIRK3), and unipolar brush cells (GIRK2/GIRK3).
      Double-labeling immunofluorescence and electron microscopies showed that GIRK
      subunits were mainly found at post-synaptic sites. Altogether, our data support
      the existence of rich GIRK molecular and cellular diversity, and provide a
      necessary framework for functional studies aimed at delineating the contribution
      of GIRK channels to synaptic inhibition in the cerebellum.

PMID- 18088367
TI  - Increased social interaction in mice deficient of the striatal medium spiny
      neuron-specific phosphodiesterase 10A2.
AB  - Cyclic nucleotide phosphodiesterase 10A (PDE10A) is a member of phosphodiesterase
      families that degrade cAMP and/or cGMP in distinct intracellular sites. PDE10A
      has a dual activity on hydrolysis of both cAMP and cGMP, and is prominently
      expressed in the striatum and the testis. Previous studies suggested that PDE10A
      is involved in regulation of locomotor activity and potentially related to
      psychosis, but concrete physiological roles of PDE10A remains elusive yet. In
      this study, we genetically inactivated PDE10A2, a prominent isoform of PDE10A in
      the brain, in mice, and demonstrate that PDE10A2 deficiency results in increased
      social interaction without any major influence on different other behaviors,
      along with increased levels of striatal cAMP. We also demonstrate that PDE10A2 is
      selectively distributed in medium spiny neurons, but not interneurons, of the
      striatal complex. Thus, our results establish a physiological role for PDE10A2 in
      regulating cAMP pathway and social interaction, and suggest that cAMP signaling
      cascade in striatal medium spiny neurons might be involved in regulating social
      interaction behavior in mice.

PMID- 18088368
TI  - Differential regulation of c-Jun N-terminal kinase and NF-kappaB pathway by
      caffeic acid phenethyl ester in astroglial and monocytic cells.
AB  - Caffeic acid phenethyl ester (CAPE), an active component of propolis extracts,
      has been known for its specific inhibition of nuclear factor kappaB (NF-kappaB)
      and subsequent anti-inflammatory activity. In this study, we report that (i) CAPE
      exerts its anti-inflammatory action (inhibition of tumor necrosis factor-induced
      expression of intercellular adhesion molecule-1 and CC chemokine ligand-2) via NF
      kappaB inhibition by two distinct molecular mechanisms in a cell-specific manner:
      CAPE inhibited downstream pathways of inhibitor kappaB (IkappaB) degradation in
      monocytic cells, while activation of upstream IkappaB kinase was suppressed by
      CAPE pre-treatment in astroglial cells; and (ii) CAPE paradoxically activates the
      c-Jun N-terminal kinase (JNK) pathway, which might be responsible for its pro
      apoptotic action and divergent regulation of proinflammatory mediators such as
      CXC chemokine ligand-8.

PMID- 18088369
TI  - Resistance of cell lines to prion toxicity aided by phospho-ERK expression.
AB  - Prion diseases are fatal neurodegenerative disorders. They are characterised by
      neuronal loss and the accumulation of an abnormal protein in the CNS. Cell lines
      exist that express the toxic form of the prion protein (PrP) with little evidence
      of cell death. Other cell based models studying the mechanism by which cell death
      occurs employ exogenous application of peptides or fragments of PrP. In this
      study, we demonstrated that full-length recombinant PrP binding manganese was
      toxic to PrP-expressing cell lines and primary neuronal cultures but not to PrP
      knockout neurones. This toxic form of PrP was also toxic to cell lines
      equivalently regardless of whether they were infected with scrapie or not. Both
      scrapie-infected cells and cells resistant to the toxicity of PrP showed
      increased levels of phosphorylated ERK protein. Scrapie-infected cells also
      showed elevated levels of caspase 12. Inhibition of phospho-ERK resulted in
      increased cell death suggesting the increased levels of phospho-ERK served a
      protective effect. These results suggest that scrapie-infected cell lines resist
      the toxicity of the prions they generate because they produce only low levels of
      abnormal protein and have increased resistance to apoptotic signs because of
      heightened activity of the MAP kinase pathway.

PMID- 18088370
TI  - Local stimulation of the adenosine A2B receptors induces an increased release of
      IL-6 in mouse striatum: an in vivo microdialysis study.
AB  - Both adenosine and interleukin-6 (IL-6) have been implicated in the
      pathophysiology of, e.g., epileptic seizures, traumatic brain injury, and
      affective disorders. Stimulation of adenosine A2B receptors on astrocytes in
      vitro leads to the increased synthesis and secretion of IL-6. We investigated
      whether or not activation of adenosine receptors evokes an increase of IL-6
      release also in vivo. 5'-N-ethylcarboxamidoadenosine, a non-specific adenosine
      agonist or vehicle was administered into the striatum of freely moving mice by
      reverse microdialysis. A statistical significant increase of the IL-6
      concentration in the perfusate was detected already 60 min after 5'-N
      ethylcarboxamidoadenosine administration. IL-6 increased progressively and
      reached a maximum after 240 min. This effect appears to be mediated through
      adenosine A2B receptors since it was counteracted by the specific A2B receptor
      antagonist MRS1706 but not by the specific A1 receptor antagonist DPCPX. We
      conclude that adenosine via activation of A2B receptors evokes IL-6 release also
      in vivo.

PMID- 18088371
TI  - TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive
      factor.
AB  - TDP-43, recently identified as a signature protein of the pathogenic inclusions
      in the brains cells of frontotemporal lobar degeneration patients, is a 43 kDa
      RNA-binding protein. It has been known mainly as a nuclear factor capable of
      repressing transcription and promoting exon exclusion. TDP-43 also forms distinct
      nuclear substructures linking different types of nuclear bodies. In this study,
      we provide the first evidence supporting TDP-43 as a neuronal activity-responsive
      factor in the dendrites of hippocampal neurons. In particular, TDP-43 resides in
      the somatodendrites mainly in the form of RNA granules colocalized with the post
      synaptic protein PSD-95. These granules also contain RNAs including at least the
      beta-actin mRNA and CaMKIIalpha mRNA. Furthermore, TDP-43 is localized in the
      dendritic processing (P) body and it behaves as a translational repressor in an
      in vitro assay. Related to this, repetitive stimuli by KCl greatly enhance the
      colocalization of TDP-43 granules with FMRP and Staufen 1, two RNA-binding
      proteins known to regulate mRNA transport and local translation in neurons. These
      data together suggest that TDP-43 is a neuronal activity-responsive factor
      functioning in the regulation of neuronal plasticity, the impairment of which
      would lead to the development of certain forms of neurodegenerative diseases
      including frontotemporal lobar degeneration.

PMID- 18088372
TI  - Assessment of post-mortem-induced changes to the mouse brain proteome.
AB  - This study was designed to assess the influence of high-energy head-focused
      microwave irradiation and the post-mortem interval on measurements of the mouse
      brain proteome. Difference gel electrophoresis was used to compare mouse brain
      protein levels in animals killed by decapitation, where the tissue was held at 25
      degrees C for selected time intervals post-mortem, and by high-energy head
      focused microwave irradiation followed by immediate resection. Microwave-mediated
      killing was used because it comprehensively snap-inactivates enzymes while
      largely retaining brain cytoarchitecture. Of the 912 protein spots common to at
      least eight of 10 gels analyzed, 35 (3.8%) showed significant differences in
      levels (t-test; p < 0.05) depending on whether animals were killed by microwave
      irradiation or decapitation. When animals were killed by decapitation, 43 protein
      spots (4.7%) showed changes in levels over the post-mortem interval (anova; p <
      0.05). The vast majority of the near 1000 proteins evident on a 2D gel were
      stable for up to 4 h. These data have important implications for studies of
      proteins in the brain, whether based on analysis of tissue derived from animal
      models or from humans.

PMID- 18088373
TI  - AMP-activated protein kinase phosphorylation in brain is dependent on method of
      killing and tissue preparation.
AB  - AMP-activated protein kinase (AMPK) is activated when the catalytic alpha subunit
      is phosphorylated on Thr172 and therefore, phosphorylation of the alpha subunit
      is used as a measure of activation. However, measurement of alpha subunit of AMPK
      (alpha-AMPK) phosphorylation in vivo can be technically challenging. To determine
      the most accurate method for measuring alpha-AMPK phosphorylation in the mouse
      brain, we compared different methods of killing and tissue preparation. We found
      that freeze/thawing samples after homogenization on ice dramatically increased
      alpha-AMPK phosphorylation in mice killed by cervical dislocation. Killing of
      mice by focused microwave irradiation, which rapidly heats the brain and causes
      enzymatic inactivation, prevented the freeze/thaw-induced increase in alpha-AMPK
      phosphorylation and similar levels of phosphorylation were observed compared with
      mice killed with cervical dislocation without freeze/thawing of samples.
      Sonication of samples in hot 1% sodium dodecyl sulfate blocked the freeze/thaw
      induced increase in alpha-AMPK phosphorylation, but phosphorylation was higher in
      mice killed by cervical dislocation compared with mice killed by focused
      microwave irradiation. These results demonstrate that alpha-AMPK phosphorylation
      is dependent on method of killing and tissue preparation and that alpha-AMPK
      phosphorylation can increase in a manner that does not reflect biological
      alterations.

PMID- 18088374
TI  - Calpain activation is involved in early caspase-independent neurodegeneration in
      the hippocampus following status epilepticus.
AB  - Evidence for increased calpain activity has been described in the hippocampus of
      rodent models of temporal lobe epilepsy. However, it is not known whether
      calpains are involved in the cell death that accompanies seizures. In this work,
      we characterized calpain activation by examining the proteolysis of calpain
      substrates and in parallel we followed cell death in the hippocampus of epileptic
      rats. Male Wistar rats were injected with kainic acid (10 mg/kg)
      intraperitoneally and killed 24 h later, after development of grade 5 seizures.
      We observed a strong Fluoro-Jade labeling in the CA1 and CA3 areas of the
      hippocampus in the rats that received kainic acid, when compared with saline
      treated rats. Immunohistochemistry and western blot analysis for the calpain
      derived breakdown products of spectrin showed evidence of increased calpain
      activity in the same regions of the hippocampus where cell death is observed. No
      evidence was found for caspase activation, in the same conditions. Treatment with
      the calpain inhibitor MDL 28170 significantly prevented the neurodegeneration
      observed in CA1. Taken together, our data suggest that early calpain activation,
      but not caspase activation, is involved in neurotoxicity in the hippocampus after
      status epilepticus.

PMID- 18088375
TI  - STAT3 activation in photoreceptors by leukemia inhibitory factor is associated
      with protection from light damage.
AB  - Members of the interleukin-6 cytokine family, including leukemia inhibitory
      factor (LIF), signal through gp130. The neuroprotective role of gp130 activation
      has been widely demonstrated in both CNS and PNS, but the mechanism by which this
      is accomplished is not well established. We investigated temporal and cell
      specific activation of signaling pathways induced by LIF in the mature mouse
      retina. Intravitreal injection of LIF preserved photoreceptor function and
      prevented photoreceptor cell death from light-induced oxidative damage in a dose
      dependent manner (2 days post-injection). A therapeutic dose of LIF induced rapid
      and sustained activation of signal transducer and activator of transcription
      (STAT) 3. Activated STAT3 was localized to all the retinal neurons and glial
      cells, including photoreceptors. Activation of extracellular signal-regulated
      kinase 1 and 2 was robust but transient in Muller glial cells, and undetectable
      at the time of light exposure. Akt was not activated by LIF. We also show that at
      the time of neuroprotection, STAT3 but not extracellular signal-regulated kinase
      1 and 2 or the Akt pathways was active in LIF-treated retinas, and activated
      STAT3 was clearly localized in transcriptionally active areas of photoreceptor
      nuclei. Our data suggest that photoreceptor protection in response to LIF can be
      directly mediated by activation of STAT3 in photoreceptors.

PMID- 18088376
TI  - The Kv4.2 mediates excitatory activity-dependent regulation of neuronal
      excitability in rat cortical neurons.
AB  - Neuronal excitability can cooperate with synaptic transmission to control the
      information storage. This regulation of neuronal plasticity can be affected by
      alterations in neuronal inputs and accomplished by modulation of voltage
      dependent ion channels. In this study, we report that enhanced excitatory input
      negatively regulated neuronal excitability. Enhanced excitatory input by
      glutamate, electric field stimulation or high K+ increased transient outward K+
      current, whereas did not affect the delayed rectifier K+ current in rat cultured
      cortical neurons. Both the voltage-dependent K+ channel 4.2 and 4.3 subunits
      contributed to the increase. The increase in the K+ current density by Kv4.2 was
      ascribed to its cytoplasmic membrane translocation, which was mediated by NMDA
      type of glutamate receptor. Furthermore, enhanced excitatory input inhibited
      neuronal excitability. Taken together, our results suggest that excitatory
      neurotransmission affects neuronal excitability via the regulation of the K+
      channel membrane translocation.

PMID- 18088377
TI  - Cytoskeletal protein carbonylation and degradation in experimental autoimmune
      encephalomyelitis.
AB  - Protein carbonylation, the non-enzymatic addition of aldehydes or ketones to
      specific amino acid residues, has been implicated in the pathophysiology of
      multiple sclerosis. In this study, we investigated whether protein carbonyls also
      accumulate in the spinal cord of Lewis rats with acute experimental autoimmune
      encephalomyelitis (EAE). Western blots analysis after derivatization with
      dinitrophenyl hydrazine (oxyblot) showed elevated protein carbonylation at the
      time of maximal clinical disability. During the same period glutathione levels
      were substantially reduced, suggesting a causal relationship between these two
      markers. In contrast, lipid peroxidation products accumulated in EAE spinal cord
      well before the appearance of neurological symptoms. Carbonyl staining was not
      restricted to inflammatory lesions but present throughout the spinal cord
      particularly in neuronal cell bodies and axons. By 2-dimensional-oxyblot, we
      identified several cytoskeletal proteins, including beta-actin, glial acidic
      fibrillary protein, and the neurofilament proteins as the major targets of
      carbonylation. These findings were confirmed by pull-down experiments, which also
      showed an increase in the number of carbonylated beta-actin molecules and a
      decrease in that of oxidized neurofilament proteins in EAE. These data suggest
      the possibility that oxidation targets neurofilament proteins for degradation,
      which may contribute to axonal pathology observed in multiple sclerosis and EAE.

PMID- 18088378
TI  - HIV-infected macrophages mediate neuronal apoptosis through mitochondrial
      glutaminase.
AB  - A significant number of patients infected with human immunodeficiency virus-1
      (HIV-1) suffer cognitive impairment ranging from mild to severe HIV-associated
      dementia (HAD), a result of neuronal degeneration in the basal ganglia, cerebral
      cortex and hippocampus. Mononuclear phagocyte dysfunction is thought to play an
      important role in the pathogenesis of HAD. Glutamate neurotoxicity is triggered
      primarily by massive Ca2+ influx arising from over-stimulation of the NMDA
      subtype of glutamate receptors. The underlying mechanisms, however, remain
      elusive. We have tested the hypothesis that mitochondrial glutaminase in HIV
      infected macrophages is involved in converting glutamine to glutamate. Our
      results demonstrate that the concentration of glutamate in HIV-1 infected
      conditioned media was dependent on glutamine dose, and HIV-1 infected conditioned
      medium mediated glutamine-dependent neurotoxicity. These results indicate HIV
      infection mediates neurotoxicity through glutamate production. In addition,
      glutamate-mediated neurotoxicity correlated with caspase activation and neuronal
      cell cycle re-activation. Inhibition of mitochondrial glutaminase diminished the
      HIV-induced glutamate production, and attenuated NMDA over-stimulation and
      subsequent neuronal apoptosis. These data implicate mitochondrial glutaminase in
      the induction of glutamate-mediated neuronal apoptosis during HIV-associated
      dementia, and provides a possible therapeutic strategy for HAD treatment.

PMID- 18088379
TI  - An update on the mechanisms of the psychostimulant effects of caffeine.
AB  - There has been a long debate about the predominant involvement of the different
      adenosine receptor subtypes and the preferential role of pre- versus post
      synaptic mechanisms in the psychostimulant effects of the adenosine receptor
      antagonist caffeine. Both striatal A(1) and A(2A) receptors are involved in the
      motor-activating and probably reinforcing effects of caffeine, although they play
      a different role under conditions of acute or chronic caffeine administration.
      The present review emphasizes the key integrative role of adenosine and adenosine
      receptor heteromers in the computation of information at the level of the
      striatal spine module (SSM). This local module is mostly represented by the
      dendritic spine of the medium spiny neuron with its glutamatergic and
      dopaminergic synapses and astroglial processes that wrap the glutamatergic
      synapse. In the SSM, adenosine acts both pre- and post-synaptically through
      multiple mechanisms, which depend on heteromerization of A(1) and A(2A) receptors
      among themselves and with D(1) and D(2) receptors, respectively. A critical
      aspect of the mechanisms of the psychostimulant effects of caffeine is its
      ability to release the pre- and post-synaptic brakes that adenosine imposes on
      dopaminergic neurotransmission by acting on different adenosine receptor
      heteromers localized in different elements of the SSM.

PMID- 18088380
TI  - Substrates dissociate dopamine transporter oligomers.
AB  - Substrate-induced endocytic trafficking of dopamine transporter (DAT) has been
      observed, but little is known about the regulation of DAT oligomerization by
      substrate. The present study investigates the effect on substrates on DAT
      oligomerization and explores a potential link with the presence of DAT at the
      cell surface in human embryonic kidney cells transiently or stably expressing N
      terminal tagged DAT constructs. Dopamine (100 microM) or amphetamine (2-10
      microM) reduced Myc-DAT coimmunoprecipitated along with Flag-DAT (oligomeric DAT)
      in tandem with a reduction in surface DAT determined by biotinylation. Dopamine
      (10-1000 microM) and amphetamine (0.2-200 microM) reduced DAT oligomerization as
      assessed by cross-linking with copper sulfate phenanthroline or Cu2+. Inhibition
      of endocytosis by 10 microM phenylarsine oxide or 450 mM sucrose counteracted the
      effect of 10 microM DA or 2 microM amphetamine in reducing DAT cross-linking. In
      addition to overall similarities between the results with the two cross-linking
      agents and between the results with the two different endocytosis inhibitors,
      some differences were noted as well, likely related to the efficiency of the
      cross-linking process and the sulfhydryl-reactive properties of phenylarsine
      oxide, respectively. The present results are the first to indicate regulation of
      oligomerization of an solute carrier family 6 transporter, the DAT, by substrates
      that act at DAT. In addition, the present study opens up the possibility of an
      important linkage between oligomerization of DAT and endocytic or other
      modulatory mechanisms impacting surface DAT.

PMID- 18088381
TI  - The GSK3 hypothesis of Alzheimer's disease.
AB  - Glycogen synthase kinase 3 (GSK3) is a constitutively active, proline-directed
      serine/threonine kinase that plays a part in a number of physiological processes
      ranging from glycogen metabolism to gene transcription. GSK3 also plays a pivotal
      and central role in the pathogenesis of both sporadic and familial forms of
      Alzheimer's disease (AD), an observation that has led us to coin the 'GSK3
      hypothesis of AD'. According to this hypothesis, over-activity of GSK3 accounts
      for memory impairment, tau hyper-phosphorylation, increased beta-amyloid
      production and local plaque-associated microglial-mediated inflammatory
      responses; all of which are hallmark characteristics of AD. If our 'GSK3
      hypothesis of AD' is substantiated and GSK3 is indeed a causal mediator of AD
      then inhibitors of GSK3 would provide a novel avenue for therapeutic intervention
      in this devastating disorder.

PMID- 18088382
TI  - Cell-to-cell cross-talk between mesenchymal stem cells and cardiomyocytes in co
      culture.
AB  - The goals of the study were: (1) to explore the communication between human
      mesenchymal stem cells (MSC) and rat cardiac myocytes resulting in
      differentiation of the stem cells and, (2) to evaluate the role of mitochondria
      in it. Light and fluorescence microscopy as well as scanning electron microscopy
      revealed that after co-cultivation, cells formed intercellular contacts and
      transient exchange with cytosolic elements could be observed. The transport of
      cytosolic entity had no specific direction. Noticeably, mitochondria also could
      be transferred to the recipient cells in a unidirectional fashion (towards
      cardiomyocytes only). Transmission electron microscopy revealed significant
      variability in both the diameter of intercellular contacting tubes and their
      shape. Inside of these nanotubes mitochondria-resembling structures were
      identified. Moreover, after co-cultivation with cardiomyocytes, expression of
      human-specific myosin was revealed in MSC. Thus, we speculate that: (1) transport
      of intracellular elements to MSC possibly can determine the direction of their
      differentiation and, (2) mitochondria may be involved in the mechanism of the
      stem cell differentiation. It looks plausible that mitochondrial transfer to
      recipient cardiomyocytes may be involved in the mechanism of failed myocardium
      repair after stem cells transplantation.

PMID- 18088383
TI  - Insights into post-translational processing of beta-galactosidase in an animal
      model resembling late infantile human G-gangliosidosis.
AB  - G(M1)-gangliosidosis is a lysosomal storage disorder caused by a deficiency of ss
      galactosidase activity. Human GM1-gangliosidosis has been classified into three
      forms according to the age of clinical onset and specific biochemical parameters.
      In the present study, a canine model for type II late infantile human GM1
      gangliosidosis was investigated 'in vitro' in detail. For a better understanding
      of the molecular pathogenesis underlying G(M1)-gangliosidosis the study focused
      on the analysis of the molecular events and subsequent intracellular protein
      trafficking of beta-galactosidase. In the canine model the genetic defect results
      in exclusion or inclusion of exon 15 in the mRNA transcripts and to translation
      of two mutant precursor proteins. Intracellular localization, processing and
      enzymatic activity of these mutant proteins were investigated. The obtained
      results suggested that the beta-galactosidase C-terminus encoded by exons 15 and
      16 is necessary for correct C-terminal proteolytic processing and enzyme activity
      but does not affect the correct routing to the lysosomes. Both mutant protein
      precursors are enzymatically inactive, but are transported to the lysosomes
      clearly indicating that the amino acid sequences encoded by exons 15 and 16 are
      necessary for correct folding and association with protective protein/cathepsin
      A, whereas the routing to the lysosomes is not influenced. Thus, the investigated
      canine model is an appropriate animal model for the human late infantile form and
      represents a versatile system to test gene therapeutic approaches for human and
      canine G(M1)-gangliosidosis.

PMID- 18088384
TI  - Neural stem cells improve neuronal survival in cultured postmortem brain tissue
      from aged and Alzheimer patients.
AB  - Neurodegenerative diseases are progressive and incurable and are becoming ever
      more prevalent. To study whether neural stem cell can reactivate or rescue
      functions of impaired neurons in the human aging and neurodegenerating brain, we
      co-cultured postmortem slices from Alzheimer patients and control participants
      with rat embryonic day 14 (E14) neural stem cells. Viability staining based on
      the exclusion of ethidium bromide by intact plasma membranes showed that there
      were strikingly more viable cells and fewer dead cells in slices co-cultured with
      neural stem cells than in untreated slices. The presence of Alzheimer pathology
      in the brain slices did not influence this effect, although the slices from
      Alzheimer patients, in general, contained fewer viable cells. Co-culturing with
      rat E14 fibroblasts did not improve the viability of neurons in the human brain
      slices. Since the human slices and neural stem cells were separated by a membrane
      during co-culturing our data show for the first time that neural stem cells
      release diffusible factors that may improve the survival of aged and degenerating
      neurons in human brains.

PMID- 18088385
TI  - CaMKIIT287 and T305 regulate history-dependent increases in alpha agonist-induced
      vascular tone.
AB  - CaMKII is a calcium and calmodulin-activated kinase that has been shown to
      regulate learning and memory in the brain, and contractility in blood vessels.
      Following Ca activation, CaMKII autophosphorylates, gaining a calcium-independent
      autonomous activity that reflects a molecular memory of having previously come
      into contact with calcium. The present study addresses whether the molecular
      memory properties of CaMKII are involved in the modulation of sustained vascular
      tone. We demonstrate a history-dependence of alpha agonist-induced vascular tone
      and show that CaMKII activation in vascular cells is also history dependent.
      Autophosphorylation of Thr287, which is classically associated with autonomous
      activity, does not persist during tone maintenance after transient increases in
      intracellular calcium levels. However, we have found that another site, Thr305,
      known from in vitro studies to be inhibitory, is regulated by alpha agonists in
      that the inhibitory action is removed, thus leading to a delayed reactivation of
      CaMKII as measured by Thr287 phosphorylation. By the use of a small molecule
      CaMKII inhibitor (KN93) as well as a decoy peptide (autoinhibitory peptide; AIP)
      we show a cause and effect relationship between CaMKII reactivation and sustained
      vascular tone maintenance. Thus, it appears that a complex interplay between the
      regulation of Thr305 and Thr287 provides a novel mechanism by which a history
      dependence is developed and contributes to a new facet of molecular memory for
      CaMKII of relevance to vascular tone maintenance.

PMID- 18088386
TI  - The functions and possible significance of Kremen as the gatekeeper of Wnt
      signalling in development and pathology.
AB  - Kremen (Krm) was originally discovered as a novel transmembrane protein
      containing the kringle domain. Both Krm1 (the first identified Krm) and its
      relative Krm2 were later identified to be the high-affinity receptors for
      Dickkopf (Dkk), the inhibitor of Wnt/beta-catenin signalling. The formation of a
      ternary complex composed of Krm, Dkk, and Lrp5/6 (the coreceptor of Wnt) inhibits
      Wnt/beta-catenin signalling. In Xenopus gastrula embryos, Wnt/beta-catenin
      signalling regulates anterior-posterior patterning, with low-signalling in
      anterior regions. Inhibition of Krm1/2 induces embryonic head defects. Together
      with anterior localization of Krms and Dkks, the inhibition of Wnt signalling by
      Dkk-Krm action seems to allow anterior embryonic development. During mammalian
      development, krm1 mRNA expression is low in the early stages, but gradually and
      continuously increases with developmental progression and differentiation. In
      contrast with the wide, strong expression of krm1 mRNA in mature tissues,
      expression of krm1 is diminished in a variety of human tumor cells. Since stem
      cells and undifferentiated cells rely on Wnt/beta-catenin signalling for
      maintenance in a low differentiation state, the physiological shutdown of
      Wnt/beta-catenin signalling by Dkk-Krm is likely to set cells on a divergent path
      toward differentiation. In tumour cells, a deficit of Krm may increase the
      susceptibility to tumourigenic transformation. Both positive and negative
      regulation of Wnt/beta-catenin signalling definitively contributes to diverse
      developmental and physiological processes, including cell-fate determination,
      tissue patterning and stem cell regulation. Krm is quite significant in these
      processes as the gatekeeper of the Wnt/beta-catenin signalling pathway.

PMID- 18088389
TI  - Antiplatelet therapy attenuates subcellular remodelling in congestive heart
      failure.
AB  - Antiplatelet agents, sarpogrelate (SAR), a 5-HT(2A) receptor antagonist, and
      cilostazol (CIL), a phosphodiesterase III (PDE-III) inhibitor, are used for the
      treatment of peripheral vascular disease. We tested whether these agents affect
      cardiac function and subcellular remodelling in congestive heart failure (CHF)
      induced by myocardial infarction (MI). Three weeks after MI, rats were treated
      daily with 5 mg/kg SAR or CIL as well as vehicle for 5 weeks. Sham-operated
      animals served as controls. At end of the treatment period, haemodynamic
      measurements were performed and the left ventricle was processed for the
      determination of sarcoplasmic reticulum (SR) Ca(2+)-uptake and -release
      activities, and expression of SR Ca(2+)-pump, phospholamban and ryanodine
      receptors, as well as myofibrillar ATPase activities, expression of alpha- and
      beta-myosin heavy chain (MHC) isoforms, and phosphorylation of phospholamban and
      cardiac troponin-I (c Tn-I). Marked haemodynamic changes in the MI-induced CHF
      were associated with depressions in SR Ca (+)-uptake and -release activities as
      well as in protein content and gene expression for SR proteins. Furthermore,
      myofibrillar Ca(2+)-stimulated ATPase activity, as well as protein content and
      gene expression for alpha-MHC were decreased whereas those for beta-MHC were
      increased in the failing heart. Also, phosphorylation levels of phospholamban and
      cTn-I were reduced in failing hearts. The MI-associated changes in cardiac
      function, SR and myofibillar activities, as well as SR and myofibrillar protein
      and gene expression were attenuated by treatment with SAR or CIL. The results
      suggest that SAR and CIL improve cardiac function by ameliorating subcellular
      remodelling in the failing heart and indicate the potential therapy of CHF with
      antiplatelet agents.

PMID- 18088391
TI  - Effect of homocysteine on calcium mobilization and   platelet function in type 2
      diabetes mellitus.
AB  - Type 2 diabetes mellitus induces a characteristic platelet hyperactivity that
      might be due to several factors including oxidative stress and abnormal
      intracellular Ca2+ homeostasis. Hyperhomocysteinaemia is considered a risk factor
      in the development of thrombosis although its effect on platelet function and the
      mechanisms involved are still poorly understood. Here we show that homocysteine
      (Hcy) induce a concentration-dependent increase in endogenous production of
      reactive oxygen species (ROS), which was significantly greater in platelets from
      diabetic patients than in controls. Platelet treatment with Hcy resulted in Ca2+
      release from the dense tubular system and the acidic stores. Ca2+ mobilisation
      induced by Hcy consisted in two components, an initial slow increase in
      intracellular free Ca2+ concentration ([Ca2+]i) and a rapid and marked increase
      in [Ca2+]i, the second leading to the activation of platelet aggregation. As well
      as ROS generation, Ca2+ mobilization and platelet aggregation were significantly
      greater in platelets from diabetic donors than in controls, which indicate that
      platelets from diabetic donors are more sensitive to Hcy. These findings,
      together with the hyperhomocysteinaemia reported in diabetic patients, strongly
      suggest that Hcy might be considered a risk factor in the development of
      cardiovascular complications associated to type 2 diabetes mellitus.

PMID- 18088390
TI  - microRNAs: a new emerging class of players for disease diagnostics and gene
      therapy.
AB  - microRNAs (miRNAs) are a new class of non-protein-coding small RNAs, which
      regulate the expression of more than 30% protein-coding genes. The unique
      expression profiles of different miRNAs in different types of cancers and at
      different stages in one cancer type suggest that miRNAs can function as novel
      biomarkers for disease diagnostics and may present a new strategy for miRNA gene
      therapy. Anti-miRNAs and antisense oligonucleotides (ASO) have been employed to
      inhibit specific miRNA expression in vitro and in vivo for investigational and
      clinical purposes. Although miRNA-based diagnostics and gene therapy are still in
      their infancy, their huge potentials will meet our need for future disease
      diagnostics and gene therapy. High efficient delivery of miRNAs into targeted
      sites, designing accurate anti-miRNA/ASOs, and related biosafety issues are three
      major challenges in this field.

PMID- 18088392
TI  - Ccr1 deficiency reduces inflammatory remodelling and preserves left ventricular
      function after myocardial infarction.
AB  - Myocardial necrosis triggers inflammatory changes and a complex cytokine cascade
      that are only incompletely understood. The chemokine receptor CCR1 mediates
      inflammatory recruitment in response to several ligands released by activated
      platelets and up-regulated after myocardial infarction (MI). Here, we assess the
      effect of CCR1 on remodelling after MI using Ccr1-deficient (Ccr1(-)(/-)) mice.
      MI was induced in Ccr1(-/-) or wild-type mice by proximal ligation of the left
      anterior descending (LAD). Mice were sacrificed and analysed at day 1, 4, 7, 14
      and 21 after MI. While initial infarct areas and areas at risk did not differ
      between groups, infarct size increased to 20.6+/-8.4% of the left ventricle (LV)
      in wild-type mice by day 21 but remained at 11.2+/-1.2% of LV (P<0.05) in Ccr1(-/
      ) mice. This attenuation in infarct expansion was associated with preserved LV
      function, as analysed by isolated heart studies according to Langendorff. Left
      ventricular developed pressure was 84.5+/-19.8 mmHg in Ccr1(-/-) mice compared to
      49.0+/-19.7 mmHg in wild-type mice (P<0.01) and coronary flow reserve was
      improved in Ccr1(-/-) mice. An altered post-infarct inflammatory pattern was
      observed in Ccr1(-/-) mice characterized by diminished neutrophil infiltration,
      accelerated monocyte/lymphocyte infiltration, decreased apoptosis, increased cell
      proliferation and earlier myofibroblast population in the infarcted tissue. In
      conclusion, functional impairment and structural remodelling after MI is reduced
      in the genetic absence of Ccr1 due to an abrogated early inflammatory recruitment
      of neutrophils and improved tissue healing, thus revealing a potential
      therapeutic target.

PMID- 18088393
TI  - Continuous glucose monitoring in patients with insulinoma.
AB  - BACKGROUND: Insulinomas are rare neuroendocrine tumours that are usually small
      and may take time to localize. They cause recurrent life-threatening spontaneous
      hypoglycaemia. Recurrent hypoglycaemia causes loss of hypoglycaemia awareness,
      putting the patient at further risk, but this has rarely been described in
      insulinoma. We describe the utility of continuous glucose monitoring (CGM) in
      patients with insulinoma. PATIENTS AND METHODS: Three patients, aged 72 years
      (patient 1), 37 years (patient 2) and 24 years (patient 3), with suspected
      insulinoma attended our investigation unit, in a university teaching hospital.
      Biochemical diagnosis was confirmed by elevated plasma insulin and C-peptide
      during biochemical hypoglycaemia [plasma glucose < 2.2 mM (40 mg/dl)]. Surgery
      confirmed histology in all. CGM was used to monitor frequency and time of
      hypoglycaemia during diagnosis and medical treatment, and after definitive
      surgical treatment. RESULTS: All patients had evidence of hypoglycaemia
      unawareness. At diagnosis in patients 1-3, CGM revealed 6.1%, 21.9% and 71.0% of
      time spent in moderate hypoglycaemia (plasma glucose 2.2-3.0 mM), and 1.4%, 11.4%
      and 48.1% of time in severe hypoglycaemia (plasma glucose < 2.2 mM),
      respectively. On diazoxide this reduced to 0.6%, 5.4% and 5.7% time in moderate
      hypoglycaemia, and no severe hypoglycaemia in patients 1 and 3, and 0.5% in
      patient 2. Octreotide therapy in patients 2 and 3 resulted in 5.8% and 0% of time
      in moderate hypoglycaemia, respectively, and no severe hypoglycaemia. After
      surgical excision CGM confirmed cure in all. CONCLUSIONS: CGM in insulinoma is
      useful in detecting hypoglycaemia, and hypoglycaemia unawareness, monitoring
      response to medical therapy and for confirming cure postoperatively, and is
      useful in the management of this uncommon but dangerous condition.

PMID- 18088394
TI  - Long-term treatment of familial male-limited precocious puberty (testotoxicosis)
      with cyproterone acetate or ketoconazole.
AB  - BACKGROUND: Familial male-limited precocious puberty (FMPP) or testotoxicosis is
      a rare gonadotrophin-independent form of sexual precocity caused by
      constitutively activating mutations of the LH receptor. Several clinical
      therapeutic approaches have been reported for this disorder, but with a paucity
      of long-term outcome data. OBJECTIVE: To evaluate the long-term treatment of
      testotoxicosis with cyproterone acetate or ketoconazole. DESIGN: A multicentric
      retrospective clinical study. PATIENTS: Ten boys from eight unrelated Brazilian
      families who carried known LH-receptor activating mutations were treated with 70
      mg/m(2) cyproterone acetate (n = 5) or 10 mg/kg ketoconazole (n = 5) for a mean
      period of 5 and 8 years, respectively. MEASUREMENTS: Chronological and bone ages,
      bone age/chronological age ratio, target height (TH) range, adult height, basal
      and GnRH-stimulated gonadotrophin levels and basal testosterone levels were
      assessed. RESULTS: Growth velocity decreased significantly during treatment with
      cyproterone acetate or ketoconazole when compared to pretreatment value in each
      group (P < 0.05). Bone age/chronological age ratio decreased significantly after
      cyproterone acetate or ketoconazole therapy. Basal testosterone levels were
      significantly lower in patients undergoing ketoconazole compared to cyproterone
      acetate treatment [0.6 +/- 0.3 nmol/l (42 +/- 21 ng/dl) vs. 5.6 +/- 4.0 nmol/l
      (392 +/- 280 ng/dl); P < 0.05], as expected. Secondary gonadotrophin-dependent
      precocious puberty occurred at a similar frequency (40%) in both groups. Five
      patients have attained adult height and two patients have already reached 90% of
      their adult height. Two of them achieved their TH range and one patient, for whom
      TH was not available, had an adult height of 0.3 SDS. Four boys (two in each
      group) did not attain their TH range. CONCLUSION: Long-term treatment with
      cyproterone acetate or ketoconazole resulted in similar outcomes without
      important side-effects in boys with testotoxicosis. However, both therapies
      showed limited efficacy in attaining normal adult height.

PMID- 18088396
TI  - Analysis of clinical, ultrasound and colour flow-Doppler characteristics in
      predicting malignancy in follicular thyroid neoplasms.

PMID- 18088395
TI  - Reduced attenuation of bone resorption after oral glucose in type 2 diabetes.
AB  - OBJECTIVE: To investigate the effect of oral glucose on bone resorption and
      osteoprotegerin (OPG) in subjects with varying degrees of glucose tolerance.
      DESIGN AND PATIENTS: In a cross-sectional study, 163 postmenopausal women aged 50
      88 years without previous history of diabetes, impaired fasting glucose (IFG) or
      impaired glucose tolerance (IGT) were recruited. All subjects underwent a 75-g
      oral glucose tolerance test (OGTT) and were then classified as having normal
      glucose tolerance (NGT), IFG, IGT or diabetes according to American Diabetes
      Association (ADA) criteria. MEASUREMENTS: Plasma glucose, serum insulin, C
      terminal telopeptide of type I collagen (CTX-I) and OPG were measured. RESULTS:
      Fasting insulin levels increased progressively from subjects with NGT, IFG/IGT to
      diabetes. After adjusted for age and body mass index (BMI), there was no
      significant difference in fasting CTX-I and OPG levels across the various degrees
      of glucose tolerance. After oral glucose, there was a significant decrease in
      serum CTX-I and OPG (P < 0.001) except for serum OPG in diabetic subjects. In
      addition, the percentages of change from baseline for both serum CTX-I and OPG
      were significantly less in diabetic subjects when compared to those in NGT
      subjects (-40.9% and 0.6% for diabetes and -50.2% and -10.6% for NGT,
      respectively). CONCLUSIONS: Oral glucose intake causes suppression of serum CTX-I
      and OPG in postmenopausal women. The effect is attenuated in women with type 2
      diabetes.

PMID- 18088397
TI  - Complex disease phenotype revealed by GH deficiency associated with a novel and
      unusual defect in the GH-1 gene.

PMID- 18088398
TI  - Gonadotrophic status in adolescents with pituitary stalk interruption syndrome.
AB  - OBJECTIVE: Pituitary stalk interruption syndrome (PSIS) is a frequent cause of GH
      deficiency (GHD) and is commonly associated with other PH deficiencies (PHDs).
      Although previous reports have correlated multiple PHDs with severe anatomical
      lesions, the status of the gonadotrophic axis has not yet been thoroughly
      analysed. METHODS: We retrospectively reviewed the medical records of 27 patients
      (15 males, 12 females) with GHD and PSIS defined by MRI findings. The status of
      the gonadotrophic axis was evaluated in children who were at least 14.5 years
      (boys) or 13 years (girls). RESULTS: Out of 27 patients, five displayed
      spontaneous full pubertal development with normal hormonal values at the final
      evaluation, whereas 22 of 27 patients (81%) had complete (n = 18) or partial
      pubertal deficiency. Three girls had primary amenorrhoea with normal
      gonadotrophin values, raising the possibility of subtle disturbances of
      gonadotrophin pulsatility. Of the 21 patients with TSH or ACTH deficiency, 17
      (81%) had complete gonadotrophin deficiency. Two of our six patients with
      apparently isolated GHD during childhood had gonadotrophin deficiency.
      Cryptorchidism was present at birth in six boys (40%). Of these six boys, one had
      normal pubertal development. Ten of 11 boys with micropenis at birth had
      gonadotrophin deficiency. CONCLUSIONS: Gonadotrophin deficiency is a common
      finding in adolescents with PSIS and is frequently associated with other PHDs.
      However its severity is variable, ranging from complete gonadotrophin deficiency
      to normogonadotrophic amenorrhoea. The occurrence of gonadotrophin deficiency in
      33% of children with apparently isolated GHD and PSIS has important implications
      for the counselling and follow-up of these patients.

PMID- 18088399
TI  - Peripheral blood cytogenetic studies in hematological neoplasms: predictors of
      obtaining metaphases for analysis.
AB  - Peripheral blood (PB) is sometimes used in place of bone marrow (BM) for
      cytogenetic studies during the evaluation of hematologic malignancies. A total of
      242 PB cytogenetic studies from adult patients were performed: clinical diagnosis
      was a myeloid neoplasm in 169 patients (70%), lymphoid or plasma cell neoplasm in
      50 (21%), and a benign/reactive cytopenia or leukocytosis in 23 (9%). PB
      cytogenetic studies resulted in at least two analyzable metaphases in 142 of the
      242 study cases (59%); in univariate analysis, this was predicted by the specific
      clinical diagnosis (P < 0.0001), presence and degree of circulating myeloid
      progenitor cells or blasts of any lineage (P < 0.0001), higher leukocyte count (P
      < 0.001), lower platelet count (P = 0.003), lower hemoglobin level (P = 0.002),
      and presence of palpable splenomegaly (P = 0.002). In multivariable analysis,
      only the presence of circulating myeloid progenitor cells or blasts sustained
      significance and this was consistent with the high yield rates seen in primary
      myelofibrosis (PMF) (80%), post-PV/ET PMF (85%), acute myeloid leukemia (76%),
      and acute lymphoblastic leukemia (80%) in contrast with the low rates seen in ET
      (0%) and PV (2%). In 104 cases, BM cytogenetic studies were performed within 1
      month of the PB cytogenetic studies; an abnormal BM cytogenetic finding was
      another independent predictor of a successful PB study (P = 0.002). PB
      cytogenetic studies are most appropriate in diseases of adults characterized by
      presence of circulating myeloid progenitors or blasts; the yield otherwise is too
      small to be cost-effective.

PMID- 18088400
TI  - Dose-escalated CHOP and tailored intensification with IFE according to early
      response and followed by BEAM/autologous stem-cell transplantation in poor-risk
      aggressive B-cell lymphoma: a prospective study from the GEL-TAMO Study Group.
AB  - OBJECTIVES: The role of high-dose therapy and autologous stem-cell
      transplantation (HDT/ASCT) in the up-front treatment of poor-risk aggressive
      lymphoma is still unknown. We conducted a prospective multi-centre trial with
      dose-escalated CHOP (MegaCHOP) and tailored intensification prior to HDT/ASCT
      according to early response assessed by CT and gallium scan (Ga67S). PATIENTS AND
      METHODS: Eighty-six patients with newly diagnosed and Ga-67 avid aggressive B
      cell lymphoma received MegaCHOP for three courses and were evaluated for response
      by CT and Ga67S. Patients with CT response and negative Ga67S received another
      MegaCHOP cycle followed by BEAM and ASCT. Those patients with positive Ga67S or
      without CT response received salvage treatment with two courses of ifosfamide and
      etoposide (IFE) followed, whenever response had been achieved, by BEAM and ASCT.
      RESULTS: Response rate before HDT/ASCT was 85% and, with 34 months of median
      follow-up, progression-free survival (PFS), overall survival (OS) and treatment
      related mortality were 56%, 64% and 7%, respectively. For transplanted patients
      (81% of the whole series), PFS and OS were 67% and 74%, respectively. No
      different outcomes were observed between patients achieving an early negative
      Ga67S response treated with MegaCHOP and BEAM/ASCT and patients with mid
      treatment positive Ga67S who received IFE prior BEAM/ASCT. CONCLUSIONS: This
      response-adapted strategy including early treatment modifications prior HDT/ASCT
      have yielded encouraging PFS and OS in patients with poor-risk B aggressive non
      Hodgkin's lymphoma.

PMID- 18088401
TI  - Gut flora, Toll-like receptors and nuclear receptors: a tripartite communication
      that tunes innate immunity in large intestine.
AB  - Separating the large intestine from gut flora is a robust layer of epithelial
      cells. This barrier is armed with an array of recognizing receptors that
      collectively set the host innate response. Here, we use nuclear receptors (NRs)
      and Toll-like receptors (TLRs), suggested to act as second messengers in the
      communication between microorganisms and epithelial cells, as probes to assess
      the impact of gut flora on innate immunity in germ-free (GF) mice. Using
      quantitative real-time polymerase chain reaction analyses, we show that 37/49 NRs
      are expressed in colonic cells of GF mice. Of these, 5 can be modulated by
      resident flora: LXRalpha, RORgamma and CAR show reduced expression and Nur77 and
      GCNF display elevated expression in conventionally raised mice compared with GF.
      Moreover, increased expression levels of TLR-2 and TLR-5 are observed in specific
      pathogen-free (SPF) mice compared with GF mice, and CAR expression is connected
      to the TLR-2 signalling pathway. Infections of GF or SPF mice with Yersinia
      pseudotuberculosis, show that GF intestinal epithelial cells fail to respond,
      except for CAR, which is downregulated. In contrast, SPF epithelial cells show a
      downregulation of all the NRs except CAR, which appears to be unaffected. Our
      findings indicate that gut flora contributes to the development of an intact
      barrier function.

PMID- 18088402
TI  - Characterization of probiotic Escherichia coli isolates with a novel pan-genome
      microarray.
AB  - BACKGROUND: Microarrays have recently emerged as a novel procedure to evaluate
      the genetic content of bacterial species. So far, microarrays have mostly covered
      single or few strains from the same species. However, with cheaper high
      throughput sequencing techniques emerging, multiple strains of the same species
      are rapidly becoming available, allowing for the definition and characterization
      of a whole species as a population of genomes--the 'pan-genome'. RESULTS: Using
      32 Escherichia coli and Shigella genome sequences we estimate the pan- and core
      genome of the species. We designed a high-density microarray in order to provide
      a tool for characterization of the E. coli pan-genome. Technical performance of
      this pan-genome microarray based on control strain samples (E. coli K-12 and
      O157:H7) demonstrated a high sensitivity and relatively low false positive rate.
      A single-channel analysis approach is robust while allowing the possibility for
      deriving presence/absence predictions for any gene included on our pan-genome
      microarray. Moreover, the array was highly sufficient to investigate the gene
      content of non-pathogenic isolates, despite the strong bias towards pathogenic E.
      coli strains that have been sequenced so far. CONCLUSION: This high-density
      microarray provides an excellent tool for characterizing the genetic makeup of
      unknown E. coli strains and can also deliver insights into phylogenetic
      relationships. Its design poses a considerably larger challenge and involves
      different considerations than the design of single strain microarrays. Here,
      lessons learned and future directions will be discussed in order to optimize
      design of microarrays targeting entire pan-genomes.

PMID- 18088403
TI  - Induction of procalcitonin in liver transplant patients treated with anti
      thymocyte globulin.
AB  - INTRODUCTION: The aim of this study was to compare the early postoperative
      kinetics of procalcitonin (PCT) and C-reactive protein (CRP) serum levels in
      patients undergoing orthotopic liver transplantation (OLTx) with different
      immunosuppressive regimens. METHODS: PCT and CRP serum concentrations were
      measured in a group of 28 OLTx recipients before induction of anesthesia, at 4
      and 8 hours following graft reperfusion, and daily until postoperative day 4. The
      same parameters were determined in 12 patients undergoing liver resection without
      conjunctive immunosuppressive therapy. Summary data are expressed as medians and
      ranges. Two-tailed nonparametric tests were performed and considered significant
      at p values of less than 0.05. RESULTS: The highest serum levels of PCT (median
      3.0 ng/mL, minimum 1.4 ng/mL, maximum 13.9 ng/mL) were found in patients after
      OLTx without ATG therapy, on postoperative day 1. In patients with ATG
      administration, PCT levels were highly increased on postoperative day 1 (median
      53.0 ng/mL, minimum 7.9 ng/mL, maximum 249.1 ng/mL). Thereafter, PCT values
      continuously decreased independently of further ATG administration in both groups
      of patients. No evidence of infection was present in either group. In 12 patients
      undergoing liver resection, peak serum PCT levels did not exceed 3.6 ng/mL. CRP
      serum levels in a group of patients with and without ATG therapy increased
      significantly on postoperative day 1, followed by a decrease. The highest levels
      of CRP were found in patients after liver resection on postoperative day 2 and
      decreased thereafter. CONCLUSION: ATG administration to patients with OLTx is
      associated with an increase in serum PCT levels, with peak values on
      postoperative day 1, and this was in the absence of any evidence of infection.
      The results of this study indicate that ATG immunosuppressive therapy is a
      stimulus for the synthesis of PCT.

PMID- 18088404
TI  - Biological characterization of two xenografts derived from human CUPs (carcinomas
      of unknown primary).
AB  - BACKGROUND: Carcinomas of unknown primary site (CUP) are epithelial malignancies
      revealed by metastatic lesions in the absence of any detectable primary tumor.
      Although they often adopt an aggressive clinical pattern, their basic biology
      remains poorly understood. Laboratory research on their biology have been
      hampered so far by the absence of cell lines representative of CUPs. METHODS: We
      attempted xenografts of CUP clinical specimens in immunodeficient mice and
      subsequent in vitro culture of transplanted malignant cells. Whenever possible,
      malignant xenografted or cultured cells were characterized by microsatellite
      genotyping, immunohistology, electron microscopy, multifish chromosome analysis
      and search of TP 53 gene mutations. RESULTS: Successful xenografts were achieved
      in 2 cases out of 4. One of them (Capi1) was lost after 3 passages whereas the
      other one (Capi3) has been adapted to in vitro culture and is currently available
      to the scientific community with reliable identification based on microsatellite
      genotyping. Both Capi1 and Capi3 have histological characteristics of
      adenocarcinomas and display intense expression of EMA, CEA and cytokeratin 7.
      Multifish chromosome analysis demonstrated a translocation involving chromosomes
      4 and 21 in both specimens. Distinct rare missense mutations of the TP53 gene
      were detected in Capi1 (codon 312) and Capi3 (codon 181); the codon 181 mutation
      is consistent with a previously reported similar finding in a small series of CUP
      specimens. Finally, intense membrane expression of c-kit was recorded in Capi3.
      CONCLUSION: Our data suggest that xenografted tumors can be obtained from a
      substantial fraction of CUP clinical specimens. The hypothesis of a preferential
      association of CUPs with TP 53 mutations of codon 181 deserves further
      investigations. The Capi3 cell line will be a useful tool for assessment of novel
      c-kit inhibitors.

PMID- 18088405
TI  - Percutaneous mechanical thrombectomy for the treatment of acute massive pulmonary
      embolism: case report.
AB  - BACKGROUND: To our knowledge we report the first case of percutaneous mechanical
      thrombectomy used for the treatment of massive pulmonary embolism in the United
      Kingdom. Pulmonary embolism is a common disease process but can be difficult to
      diagnose. Massive pulmonary embolism presenting with profound hypotension,
      however, is rare. Both phenomena carry with them significant mortality.
      Traditionally those patients suffering haemodynamic compromise from pulmonary
      embolism are treated with intravenous or catheter-directed thrombolysis. When
      this is contraindicated surgical embolectomy or mechanical techniques via a right
      heart catheter are alternative options. The former is well established but the
      latter is less commonly utilised in clinical practice. Our aim is to highlight
      the effectiveness and relative safety of percutaneous mechanical thrombectomy as
      a therapeutic tool in massive pulmonary embolism. CASE PRESENTATION: A 70 year
      old gentleman presented with a 4-month history of dry cough and general malaise.
      Clinical examination along with routine chest radiograph confirmed a left pleural
      effusion which was drained. Computed tomography of the chest, abdomen and pelvis
      revealed a left renal mass consistent with renal cell carcinoma plus multiple
      metastatic subpleural nodules. Following planned thoracoscopy and pleural biopsy
      the patient became acutely dyspnoeic and hypotensive. Relevant investigations
      including computed tomography pulmonary angiogram confirmed a large saddle
      embolus extending in to the lobar branches of both left and right pulmonary
      arteries. There were several relative contraindications to thrombolysis and so
      the patient proceeded to have percutaneous mechanical thrombectomy with excellent
      results. The patient made a full recovery from the acute episode and was
      discharged home on warfarin with a view to planned cyto-reductive nephrectomy.
      CONCLUSION: We illustrate here that percutaneous mechanical thrombectomy can be a
      safe and effective method of treating massive pulmonary embolism when
      thrombolysis is relatively contraindicated. It may also be of use as an adjuvant
      therapy in those patients able to receive thrombolysis. In the future further
      evaluation involving a larger cohort of subjects is necessary to determine
      whether this treatment is superior to surgical embolectomy when thrombolysis
      cannot be performed.

PMID- 18088406
TI  - Absence of autoantibodies connected to autoimmune polyendocrine syndrome type I
      and II and Addison's disease in girls and women with Turner syndrome.
AB  - BACKGROUND: A disturbance in the immune system has been described in Turner
      syndrome (45,X), with an association to low levels of IgG and IgM and decreased
      levels of T- and B-lymphocytes. Also different autoimmune diseases have been
      connected to Turner syndrome (45,X), thyroiditis being the most common. Other
      autoimmune diseases seen are inflammatory bowel disease, insulin dependent
      diabetes mellitus, Addison's disease, rheumatoid arthritis, myasthenia gravis,
      vitiligo, alopecia, pernicious anaemia and hypoparathyroidism, but the
      association to Turner syndrome is not definite. Besides the typical features of
      Turner syndrome (short stature, failure to enter puberty spontaneously and
      infertility due to ovarian insufficiency) ear problems are common. Otitis media
      and a progressive sensorineural hearing disorder are commonly seen. In the normal
      population there are known inner ear disorders related to autoimmune diseases.
      The aim of this study was to investigate patients with Turner syndrome regarding
      autoantibodies connected to the autoimmune disorders; autoimmune polyendocrine
      syndrome type I and II and Addison's disease, to screen for overlapping profile
      of autoantibodies. Blood samples from 110 Turner patients (7-65 years) were
      investigated using in vitro transcription, translation and immunoprecipitation
      techniques regarding autoantibodies connected to autoimmune polyendocrine
      syndrome type I and II and Addison's disease (21-hydroxylase, 17alpha
      hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase,
      tyrosine hydroxylase and tryptophan hydroxylase). RESULTS: The autoantibodies
      investigated were not overrepresented among the Turner patients. CONCLUSION: The
      autoimmune disorders associated with Turner syndrome do not seem to be of the
      same origin as Addison's disease, the type I or II autoimmune polyendocrine
      syndrome.

PMID- 18088407
TI  - 'I believe that the staff have reduced their closeness to patients': an
      exploratory study on the impact of HIV/AIDS on staff in four rural hospitals in
      Uganda.
AB  - BACKGROUND: Staff shortages could harm the provision and quality of health care
      in Uganda, so staff retention and motivation are crucial. Understanding the
      impact of HIV/AIDS on staff contributes to designing appropriate retention and
      motivation strategies. This research aimed 'to identify the influence of HIV/AIDS
      on staff working in general hospitals at district level in rural areas and to
      explore support required and offered to deal with HIV/AIDS in the workplace'. Its
      results were to inform strategies to mitigate the impact of HIV/AIDS on hospital
      staff. METHODS: A cross-sectional study with qualitative and quantitative
      components was implemented during two weeks in September 2005. Data were
      collected in two government and two faith-based private not-for-profit hospitals
      purposively selected in rural districts in Uganda's Central Region. Researchers
      interviewed 237 people using a structured questionnaire and held four focus group
      discussions and 44 in-depth interviews. RESULTS: HIV/AIDS places both physical
      and, to some extent, emotional demands on health workers. Eighty-six per cent of
      respondents reported an increased workload, with 48 per cent regularly working
      overtime, while 83 per cent feared infection at work, and 36 per cent reported
      suffering an injury in the previous year. HIV-positive staff remained in hiding,
      and most staff did not want to get tested as they feared stigmatization.
      Organizational responses were implemented haphazardly and were limited to
      providing protective materials and the HIV/AIDS-related services offered to
      patients. Although most staff felt motivated to work, not being motivated was
      associated with a lack of daily supervision, a lack of awareness on the
      availability of HIV/AIDS counselling, using antiretrovirals and working overtime.
      The specific hospital context influenced staff perceptions and experiences.
      CONCLUSION: HIV/AIDS is a crucially important contextual factor, impacting on
      working conditions in various ways. Therefore, organizational responses should be
      integrated into responses to other problematic working conditions and adapted to
      the local context. Opportunities already exist, such as better use of
      supervision, educational sessions and staff meetings. However, exchanges on
      interventions to improve staff motivation and address HIV/AIDS in the health
      sector are urgently required, including information on results and details of the
      context and implementation process.

PMID- 18088408
TI  - Literature Lab: a method of automated literature interrogation to infer biology
      from microarray analysis.
AB  - BACKGROUND: The biomedical literature is a rich source of associative information
      but too vast for complete manual review. We have developed an automated method of
      literature interrogation called "Literature Lab" that identifies and ranks
      associations existing in the literature between gene sets, such as those derived
      from microarray experiments, and curated sets of key terms (i.e. pathway names,
      medical subject heading (MeSH) terms, etc). RESULTS: Literature Lab was developed
      using differentially expressed gene sets from three previously published cancer
      experiments and tested on a fourth, novel gene set. When applied to the genesets
      from the published data including an in vitro experiment, an in vivo mouse
      experiment, and an experiment with human tumor samples, Literature Lab correctly
      identified known biological processes occurring within each experiment. When
      applied to a novel set of genes differentially expressed between locally invasive
      and metastatic prostate cancer, Literature Lab identified a strong association
      between the pathway term "FOSB" and genes with increased expression in metastatic
      prostate cancer. Immunohistochemistry subsequently confirmed increased nuclear
      FOSB staining in metastatic compared to locally invasive prostate cancers.
      CONCLUSION: This work demonstrates that Literature Lab can discover key
      biological processes by identifying meritorious associations between
      experimentally derived gene sets and key terms within the biomedical literature.

PMID- 18088409
TI  - Semaphorin6A acts as a gate keeper between the central and the peripheral nervous
      system.
AB  - BACKGROUND: During spinal cord development, expression of chicken SEMAPHORIN6A
      (SEMA6A) is almost exclusively found in the boundary caps at the ventral motor
      axon exit point and at the dorsal root entry site. The boundary cap cells are
      derived from a population of late migrating neural crest cells. They form a
      transient structure at the transition zone between the peripheral nervous system
      (PNS) and the central nervous system (CNS). Ablation of the boundary cap resulted
      in emigration of motoneurons from the ventral spinal cord along the ventral
      roots. Based on its very restricted expression in boundary cap cells, we tested
      for a role of Sema6A as a gate keeper between the CNS and the PNS. RESULTS:
      Downregulation of Sema6A in boundary cap cells by in ovo RNA interference
      resulted in motoneurons streaming out of the spinal cord along the ventral roots,
      and in the failure of dorsal roots to form and segregate properly. PlexinAs
      interact with class 6 semaphorins and are expressed by both motoneurons and
      sensory neurons. Knockdown of PlexinA1 reproduced the phenotype seen after loss
      of Sema6A function both at the ventral motor exit point and at the dorsal root
      entry site of the lumbosacral spinal cord. Loss of either PlexinA4 or Sema6D
      function had an effect only at the dorsal root entry site but not at the ventral
      motor axon exit point. CONCLUSION: Sema6A acts as a gate keeper between the PNS
      and the CNS both ventrally and dorsally. It is required for the clustering of
      boundary cap cells at the PNS/CNS interface and, thus, prevents motoneurons from
      streaming out of the ventral spinal cord. At the dorsal root entry site it
      organizes the segregation of dorsal roots.

PMID- 18088410
TI  - Histogenesis of retinal dysplasia in trisomy 13.
AB  - BACKGROUND: Although often associated with holoprosencephaly, little detail of
      the histopathology of cyclopia is available. Here, we describe the ocular
      findings in a case of trisomy 13 to better understand the histogenesis of the
      rosettes, or tubules, characteristic of the retinal dysplasia associated with
      this condition. METHODS: A full pediatric autopsy was performed of a near term
      infant who died shortly after birth from multiple congenital anomalies including
      fused facial-midline structures. A detailed histopathological study of the ocular
      structures was performed. The expression of interphotoreceptor retinoid-binding
      protein (IRBP), cellular retinal-binding protein (CRALBP), rod opsin, and Sonic
      Hedgehog (Shh) were studied by immunohistochemistry. RESULTS: Holoprosencephaly,
      and a spectrum of anatomical findings characteristic of Patau's syndrome, were
      found. Cytogenetic studies demonstrated trisomy 13 [47, XY, +13]. The eyes were
      fused but contained two developed separate lenses. In contrast, the cornea, and
      angle structures were hypoplastic, and the anterior chamber had failed to form.
      The retina showed areas of normally laminated neural retina, whereas in other
      areas it was replaced by numerous neuronal rosettes. Histological and
      immunohistochemical studies revealed that the rosettes were composed of
      differentiated retinal neurons and Muller cell glia. In normally laminated
      retina, Shh expression was restricted to retinal-ganglion cells, and to a
      population of neurons in the inner zone of the outer nuclear layer. In contrast,
      Shh could not be detected in the dysplastic rosettes. CONCLUSION: The
      histopathology of cyclopia appears to be more complex than what may have been
      previously appreciated. In fact, the terms "cyclopia" and "synophthalmia" are
      misnomers as the underlying mechanism is a failure of the eyes to form separately
      during development. The rosettes found in the dysplastic retina are fundamentally
      different than those of retinoblastoma, being composed of a variety of
      differentiated cell types. The dysplastic rosettes are essentially laminated
      retina failing to establish a polarized orientation, resulting in the formation
      of tubules. Finally, our findings suggest that defective ganglion cell Shh
      expression may contribute to the ocular pathology of cyclopia.

PMID- 18088411
TI  - A prospective pilot clinical trial evaluating the utility of a dynamic near
      infrared imaging device for characterizing suspicious breast lesions.
AB  - INTRODUCTION: Characterizing and differentiating between malignant tumors, benign
      tumors, and normal breast tissue is increasingly important in the patient
      presenting with breast problems. Near-infrared diffuse optical imaging and
      spectroscopy is capable of measuring multiple physiologic parameters of
      biological tissue systems and may have clinical applications for assessing the
      development and progression of neoplastic processes, including breast cancer. The
      currently available application of near-infrared imaging technology for the
      breast, however, is compromised by low spatial resolution, tissue heterogeneity,
      and interpatient variation. MATERIALS AND METHODS: We tested a dynamic near
      infrared imaging schema for the characterization of suspicious breast lesions
      identified on diagnostic clinical ultrasound. A portable handheld near-infrared
      tissue imaging device (P-Scan; ViOptix Inc., Fremont, CA, USA) was utilized. An
      external mechanical compression force was applied to breast tissue. The tissue
      oxygen saturation and hemoglobin concentration were recorded simultaneously by
      the handheld near-infrared imaging device. Twelve categories of dynamic tissue
      parameters were derived based on real-time measurements of the tissue hemoglobin
      concentration and the oxygen saturation. RESULTS: Fifty suspicious breast lesions
      were evaluated in 48 patients. Statistical analyses were carried out on 36 out of
      50 datasets that satisfied our inclusion criteria. Suspicious breast lesions
      identified on diagnostic clinical ultrasound had lower oxygenation and higher
      hemoglobin concentration than the surrounding normal breast tissue. Furthermore,
      histopathologic-proven malignant breast tumors had a lower differential
      hemoglobin contrast (that is, the difference of hemoglobin concentration
      variability between the suspicious breast lesion and the normal breast parenchyma
      located remotely elsewhere within the ipsilateral breast) as compared with
      histopathologic-proven benign breast lesions. CONCLUSION: The proposed dynamic
      near-infrared imaging schema has the potential to differentiate benign processes
      from those of malignant breast tumors. Further development and refinement of the
      dynamic imaging device and additional subsequent clinical testing are necessary
      for optimizing the accuracy of detection.

PMID- 18088412
TI  - Androgen secreting steroid cell tumor of the ovary in a young lactating women
      with acute onset of severe hyperandrogenism: a case report and review of
      literature.
AB  - INTRODUCTION: Steroid cell tumors of the ovary account for less than 0.1% of all
      ovarian tumors 1 and these tumours may present at any age in association with
      interesting presentations related to the hormonal activity and virilizing
      properties of tumor. Hayes and Scully 2 reported 63 cases in patients ranging
      from 2 to 80 years of age. The subtype, not otherwise specified, is associated
      with androgenic changes in approximately one half of patients with this tumour 1.
      In a series of 63 cases from Massachusetts General Hospital, 94% of the tumors
      were found to be unilateral and 28.6% were malignant 3. As most of these tumors
      are diagnosed at an early stage and do not recur or metastasize, little is known
      about their response to therapies such as chemotherapy or radiation 3. CASE
      PRESENTATION: We present the case of a 22-year old lactating woman who presented
      with four months of amenorrhea associated with signs of virilization. Clinical
      and diagnostic evaluation revealed a right adenexal mass and elevated serum
      levels of testosterone and she was diagnosed as having a stage 1A androgen
      secreting steroid cell tumor. In view of the early stage of the disease, she
      underwent right salpingo-oopherectomy. Histopathological examination and
      immunohistochemistry confirmed the diagnosis. Two months after surgery she
      regained normal menses and showed regression of the androgenic changes.
      CONCLUSION: Surgery remains the mainstay of the treatment of gonadotrophin
      receptor positive steroid cell tumors although medical therapy using
      Gonadotrophin Releasing Hormone [GnRH analogues has been tried recently in
      recurrent or inoperable cases. There is no described effective chemotherapy or
      radiotherapy for this condition.

PMID- 18088413
TI  - Desymmetrization of 7-azabicycloalkenes by tandem olefin metathesis for the
      preparation of natural product scaffolds.
AB  - BACKGROUND: Tandem olefin metathesis sequences are known to be versatile for the
      generation of natural product scaffolds and have also been used for ring opening
      of strained carbo- and heterocycles. In this paper we demonstrate the potential
      of these reactions for the desymmetrization of 7-azabicycloalkenes. RESULTS: We
      have established efficient protocols for the desymmetrization of different 7
      azabicycloalkenes by intra- and intermolecular tandem metathesis sequences with
      ruthenium based catalysts. CONCLUSION: Desymmetrization of 7-azabicycloalkenes by
      olefin metathesis is an efficient process for the preparation of common natural
      product scaffolds such as pyrrolidines, indolizidines and isoindoles.

PMID- 18088414
TI  - On 50th anniversary of the global carbon dioxide record.
AB  - The 50-year global CO2 record led the way in establishing a scientific fact:
      modern civilization is changing important properties of the global atmosphere,
      oceans and biosphere. The evidence on which this scientific fact is based will be
      refined further, but the next challenge for scientists is broader. In addition to
      its traditional role in providing discovery, diagnosis, and prediction of the
      changes that are taking place on our planet, science has now also a role in
      helping society mitigate emissions by objectively quantifying them, and in
      helping adaptation by providing environmental forecasts on regional scales.
      Science is also expected to provide new options for society to tackle the
      transition to a new energy system, and to provide thorough environmental
      evaluation of all such options. This is what the meeting recognized as planetary
      responsibilities for scientists in the next 50 years.

PMID- 18088415
TI  - Genomic imbalances in 5918 malignant epithelial tumors: an explorative meta
      analysis of chromosomal CGH data.
AB  - BACKGROUND: Chromosomal abnormalities have been associated with most human
      malignancies, with gains and losses on some genomic regions associated with
      particular entities. METHODS: Of the 15429 cases collected for the Progenetix
      molecular-cytogenetic database, 5918 malignant epithelial neoplasias analyzed by
      chromosomal Comparative Genomic Hybridization (CGH) were selected for further
      evaluation. For the 22 clinico-pathological entities with more than 50 cases,
      summary profiles for genomic imbalances were generated from case specific data
      and analyzed. RESULTS: With large variation in overall genomic instability,
      recurring genomic gains and losses were prominent. Most entities showed frequent
      gains involving 8q2, while gains on 20q, 1q, 3q, 5p, 7q and 17q were frequent in
      different entities. Loss "hot spots" included 3p, 4q, 13q, 17p and 18q among
      others. Related average imbalance patterns were found for clinically distinct
      entities, e.g. hepatocellular carcinomas (ca.) and ductal breast ca., as well as
      for histologically related entities (squamous cell ca. of different sites).
      CONCLUSION: Although considerable case-by-case variation of genomic profiles can
      be found by CGH in epithelial malignancies, a limited set of variously combined
      chromosomal imbalances may be typical for carcinogenesis. Focus on the respective
      regions should aid in target gene detection and pathway deduction.

PMID- 18088416
TI  - Towards an understanding of salient neighborhood boundaries: adolescent reports
      of an easy walking distance and convenient driving distance.
AB  - Numerous studies have examined the association between the surrounding
      neighborhood environment and physical activity levels in adolescents. Many of
      these studies use a road network buffer or Euclidean distance buffer around an
      adolescent's home to represent the appropriate geographic area for study (i.e.,
      neighborhood). However, little empirical research has examined the appropriate
      buffer size to use when defining this area and there is little consistency across
      published research as to the buffer size used. In this study, 909 12th grade
      adolescent girls of diverse racial and geographic backgrounds were asked to
      report their perceptions of an easy walking distance and a convenient driving
      distance. These two criterions are often used as the basis for defining one's
      neighborhood.The mean easy walking distance in minutes reported by adolescent
      girls was 14.8 minutes (SD = 8.7). The mean convenient driving distance in
      minutes reported was 17.9 minutes (SD = 10.8). Nested linear multivariate
      regression models found significant differences in reported 'easy walking
      distance' across race and BMI. White adolescents reported on average almost 2
      minutes longer for an easy walking distance compared to African American
      adolescents. Adolescents who were not overweight or at risk for overweight
      reported almost 2 minutes fewer for an easy walking distance relative to those
      who were overweight or at risk for overweight. Significant differences by urban
      status were found in the reported 'convenient driving distance'. Those living in
      non-urban areas reported on average 3.2 minutes more driving time as convenient
      compared to those living in urban areas. Very little variability in reported
      walking and driving distances was explained by the predictors used in the models
      (i.e., age, race, BMI, physical activity levels, urban status and SES).This study
      suggests the use of a 0.75 mile buffer to represent an older female adolescent's
      neighborhood, which can be accessed through walking. However, determining the
      appropriate area inclusive of car travel should be tailored to the geographic
      location of the adolescent since non-urban adolescents are willing to spend more
      time driving to destinations. Further research is needed to understand the
      substantial variability across adolescent perceptions of an easy walking and
      convenient driving distance.

PMID- 18088418
TI  - Predicting toxicity through computers: a changing world.
AB  - The computational approaches used to predict toxicity are evolving rapidly, a
      process hastened on by the emergence of new ways of describing chemical
      information. Although this trend offers many opportunities, new regulations, such
      as the European Community's 'Registration, Evaluation, Authorization and
      Restriction of Chemicals' (REACH), demand that models be ever more robust. In
      this commentary, we outline the numerous factors involved in the evolution of
      quantitative structure-regulatory activity relationship (QSAR) models. Such
      models not only require powerful tools, but must also be adapted for their
      intended application, such as in using suitable input values and having an output
      that complies with legal requirements. In addition, transparency and model
      reproducibility are important factors. As more models become available, it is
      vital that new theoretical possibilities are embraced, and efforts are combined
      in order to promote new flexible, modular tools.

PMID- 18088417
TI  - Conserved and divergent patterns of expression of DAZL, VASA and OCT4 in the germ
      cells of the human fetal ovary and testis.
AB  - BACKGROUND: Germ cells arise from a small group of cells that express markers of
      pluripotency including OCT4. In humans formation of gonadal compartments (cords
      in testis, nests in ovary) takes place during the 1st trimester (6-8 weeks
      gestation). In the 2nd trimester germ cells can enter meiotic prophase in females
      whereas in males this does not occur until puberty. We have used qRTPCR, Westerns
      and immunohistochemical profiling to determine which of the germ cell subtypes in
      the human fetal gonads express OCT4, DAZL and VASA, as these have been shown to
      play an essential role in germ cell maturation in mice. RESULTS: OCT4 mRNA and
      protein were detected in extracts from both 1st and 2nd trimester ovaries and
      testes. In ovarian extracts a marked increase in expression of VASA and DAZL mRNA
      and protein occurred in the 2nd trimester. In testicular extracts VASA mRNA and
      protein were low/undetectable in 1st trimester and increased in the 2nd trimester
      whereas the total amount of DAZL did not seem to change. During the 1st
      trimester, germ cells were OCT4 positive but did not express VASA. These results
      are in contrast to the situation in mice where expression of Vasa is initiated in
      Oct4 positive primordial germ cells as they enter the gonadal ridge. In the 2nd
      trimester germ cells with intense cytoplasmic staining for VASA were present in
      both sexes; these cells were OCT4 negative. DAZL expression overlapped with both
      OCT4 and VASA and changed from the nuclear to the cytoplasmic compartment as
      cells became OCT4-negative. In males, OCT4-positive and VASA-positive
      subpopulations of germ cells coexisted within the same seminiferous cords but in
      the ovary there was a distinct spatial distribution of cells with OCT4 expressed
      by smaller, peripherally located, germ cells whereas DAZL and VASA were
      immunolocalised to larger (more mature) centrally located cells. CONCLUSION:
      OCT4, DAZL and VASA are expressed by human fetal germ cells but their patterns of
      expression are temporally and spatially distinct. In the 1st trimester OCT4 was
      detected in most germ cells. In the 2nd trimester the onset of expression of VASA
      was associated with the formation of oocytes and spermatogonia both of which were
      OCT-4 negative. Relocation of DAZL from nucleus to cytoplasm paralleled the down
      regulation of OCT4 and the onset of expression of VASA. These data reveal
      similarities between the expression of key regulatory proteins within germ cells
      as they mature in male and female fetal human gonads suggesting that in the
      female these maturational changes are not determined by entry into meiosis.

PMID- 18088419
TI  - Construction and characterization of an expressed sequenced tag library for the
      mosquito vector Armigeres subalbatus.
AB  - BACKGROUND: The mosquito, Armigeres subalbatus, mounts a distinctively robust
      innate immune response when infected with the nematode Brugia malayi, a causative
      agent of lymphatic filariasis. In order to mine the transcriptome for new insight
      into the cascade of events that takes place in response to infection in this
      mosquito, 6 cDNA libraries were generated from tissues of adult female mosquitoes
      subjected to immune-response activation treatments that lead to well
      characterized responses, and from aging, naive mosquitoes. Expressed sequence
      tags (ESTs) from each library were produced, annotated, and subjected to
      comparative analyses. RESULTS: Six libraries were constructed and used to
      generate 44,940 expressed sequence tags, of which 38,079 passed quality filters
      to be included in the annotation project and subsequent analyses. All of these
      sequences were collapsed into clusters resulting in 8,020 unique sequence
      clusters or singletons. EST clusters were annotated and curated manually within
      ASAP (A Systematic Annotation Package for Community Analysis of Genomes) web
      portal according to BLAST results from comparisons to Genbank, and the Anopheles
      gambiae and Drosophila melanogaster genome projects. CONCLUSION: The resulting
      dataset is the first of its kind for this mosquito vector and provides a basis
      for future studies of mosquito vectors regarding the cascade of events that
      occurs in response to infection, and thereby providing insight into vector
      competence and innate immunity.

PMID- 18088420
TI  - Mosquito transcriptome changes and filarial worm resistance in Armigeres
      subalbatus.
AB  - BACKGROUND: Armigeres subalbatus is a natural vector of the filarial worm Brugia
      pahangi, but it rapidly and proficiently kills Brugia malayi microfilariae by
      melanotic encapsulation. Because B. malayi and B. pahangi are morphologically and
      biologically similar, the Armigeres-Brugia system serves as a valuable model for
      studying the resistance mechanisms in mosquito vectors. We have initiated
      transcriptome profiling studies in Ar. subalbatus to identify molecular
      components involved in B. malayi refractoriness. RESULTS: These initial studies
      assessed the transcriptional response of Ar. subalbatus to B. malayi at 1, 3, 6,
      12, 24, 48, and 72 hrs after an infective blood feed. In this investigation, we
      initiated the first holistic study conducted on the anti-filarial worm immune
      response in order to effectively explore the functional roles of immune-response
      genes following a natural exposure to the parasite. Studies assessing the
      transcriptional response revealed the involvement of unknown and conserved
      unknowns, cytoskeletal and structural components, and stress and immune
      responsive factors. The data show that the anti-filarial worm immune response by
      Ar. subalbatus to be a highly complex, tissue-specific process involving varied
      effector responses working in concert with blood cell-mediated melanization.
      CONCLUSION: This initial study provides a foundation and direction for future
      studies, which will more fully dissect the nature of the anti-filarial worm
      immune response in this mosquito-parasite system. The study also argues for
      continued studies with RNA generated from both hemocytes and whole bodies to
      fully expound the nature of the anti-filarial worm immune response.

PMID- 18088421
TI  - Application of the comprehensive set of heterozygous yeast deletion mutants to
      elucidate the molecular basis of cellular chromium toxicity.
AB  - BACKGROUND: The serious biological consequences of metal toxicity are well
      documented, but the key modes of action of most metals are unknown. To help
      unravel molecular mechanisms underlying the action of chromium, a metal of major
      toxicological importance, we grew over 6,000 heterozygous yeast mutants in
      competition in the presence of chromium. Microarray-based screens of these
      heterozygotes are truly genome-wide as they include both essential and non
      essential genes. RESULTS: The screening data indicated that proteasomal (protein
      degradation) activity is crucial for cellular chromium (Cr) resistance. Further
      investigations showed that Cr causes the accumulation of insoluble and toxic
      protein aggregates, which predominantly arise from proteins synthesised during Cr
      exposure. A protein-synthesis defect provoked by Cr was identified as mRNA
      mistranslation, which was oxygen-dependent. Moreover, Cr exhibited synergistic
      toxicity with a ribosome-targeting drug (paromomycin) that is known to act via
      mistranslation, while manipulation of translational accuracy modulated Cr
      toxicity. CONCLUSION: The datasets from the heterozygote screen represent an
      important public resource that may be exploited to discover the toxic mechanisms
      of chromium. That potential was validated here with the demonstration that mRNA
      mistranslation is a primary cause of cellular Cr toxicity.

PMID- 18088422
TI  - The Roman Bridge: a "double pulley - suture bridges" technique for rotator cuff
      repair.
AB  - BACKGROUND: With advances in arthroscopic surgery, many techniques have been
      developed to increase the tendon-bone contact area, reconstituting a more
      anatomic configuration of the rotator cuff footprint and providing a better
      environment for tendon healing. METHODS: We present an arthroscopic rotator cuff
      repair technique which uses suture bridges to optimize rotator cuff tendon
      footprint contact area and mean pressure. RESULTS: Two medial row 5.5-mm Bio
      Corkscrew suture anchors (Arthrex, Naples, FL), which are double-loaded with No.
      2 FiberWire sutures (Arthrex, Naples, FL), are placed in the medial aspect of the
      footprint. Two suture limbs from a single suture are both passed through a single
      point in the rotator cuff. This is performed for both anchors. The medial row
      sutures are tied using the double pulley technique. A suture limb is retrieved
      from each of the medial anchors through the lateral portal, and manually tied as
      a six-throw surgeon's knot over a metal rod. The two free suture limbs are pulled
      to transport the knot over the top of the tendon bridge. Then the two free suture
      limbs that were used to pull the knot down are tied. The end of the sutures are
      cut. The same double pulley technique is repeated for the other two suture limbs
      from the two medial anchors, but the two free suture limbs are used to produce
      suture bridges over the tendon, by means of a Pushlock (Arthrex, Naples, FL),
      placed 1 cm distal to the lateral edge of the footprint. CONCLUSION: This
      technique maximizes the advantages of two techniques. On the one hand, the double
      pulley technique provides an extremely secure fixation in the medial aspect of
      the footprint. On the other hand, the suture bridges allow to improve pressurized
      contact area and mean footprint pressure. In this way, the bony footprint in not
      compromised by the distal-lateral fixation, and it is thus possible to share the
      load between fixation points. This maximizes the strength of the repair and
      provides a barrier preventing penetration of synovial fluid into the healing area
      of tendon and bone.

PMID- 18088423
TI  - Contribution of migrant coffee labourers infected with Onchocerca volvulus to the
      maintenance of the microfilarial reservoir in an ivermectin-treated area of
      Mexico.
AB  - BACKGROUND: Since 1991, in Mexico, ivermectin has been administered twice a year
      to all residents in the onchocerciasis endemic foci which are mainly located in
      the coffee growing areas. However, the presence of a potentially infected
      itinerant seasonal labour force which is not treated regularly could jeopardise
      the attainment of the 85% coverage which is the present target for elimination of
      the disease. METHODS: The prevalence and intensity of Onchocerca volvulus
      microfilariae (mf), as well as their transmission from humans to vectors, were
      assessed during the coffee planting-clearing and harvesting seasons of 1997-1998,
      and 1998-1999 in two localities (I and II) of Southern Chiapas, Mexico, which
      regularly receive an influx of untreated migrant coffee labourers. RESULTS:
      Localities I and II had, respectively, an average of 391 (+/- 32) and 358 (+/-
      14) resident inhabitants, and 70 (+/- 52) and 498 (+/- 289) temporary labourers.
      The ratio of migrants to residents ranged from 0.1:1 in locality I to 2.4:1 in
      locality II. The proportion of infected Simulium ochraceum s.l. parous flies was
      significantly lower in locality I than in locality II, and significantly higher
      during the stay of the migrants than before their arrival or after their
      departure. Parity and infection were higher in May-July than in November-February
      (in contrast with the latter being typically considered as the peak
      onchocerciasis transmission season by S. ochraceum s.l.). CONCLUSION: The
      presence of significant numbers of untreated and potentially infected migrants
      may contribute to ongoing transmission, and their incorporation into ivermectin
      programmes should be beneficial for the attainment of the elimination goals of
      the regional initiative. However, the possibility that the results also reflect
      transmission patterns for the area cannot be excluded and these should be
      analyzed further.

PMID- 18088424
TI  - Profiling sex-biased gene expression during parthenogenetic reproduction in
      Daphnia pulex.
AB  - BACKGROUND: Sexual reproduction is a core biological function that is conserved
      throughout eukaryotic evolution, yet breeding systems are extremely variable.
      Genome-wide comparative studies can be effectively used to identify genes and
      regulatory patterns that are constrained to preserve core functions from those
      that may help to account for the diversity of animal reproductive strategies. We
      use a custom microarray to investigate gene expression in males and two
      reproductive stages of females in the crustacean Daphnia pulex. Most Daphnia
      species reproduce by cyclical parthenogenesis, alternating between sexual and
      clonal reproduction. Both sex determination and the switch in their mode of
      reproduction is environmentally induced, making Daphnia an interesting
      comparative system for the study of sex-biased and reproductive genes. RESULTS:
      Patterns of gene expression in females and males reveal that 50% of assayed
      transcripts show some degree of sex-bias. Female-biased transcription is enriched
      for translation, metabolic and regulatory genes associated with development. Male
      biased expression is enriched for cuticle and protease function. Comparison with
      well studied arthropods such as Drosophila melanogaster and Anopheles gambiae
      suggests that female-biased patterns tend to be conserved, whereas male-biased
      genes are evolving faster in D. pulex. These findings are based on the proportion
      of female-biased, male-biased, and unbiased genes that share sequence similarity
      with proteins in other animal genomes. CONCLUSION: Some transcriptional
      differences between males and females appear to be conserved across Arthropoda,
      including the rapid evolution of male-biased genes which is observed in insects
      and now in a crustacean. Yet, novel patterns of male-biased gene expression are
      also uncovered. This study is an important first step towards a detailed
      understanding of the genetic basis and evolution of parthenogenesis,
      environmental sex determination, and adaptation to aquatic environments.

PMID- 18088425
TI  - Sphingomyelin phosphodiesterase-1 (SMPD1) coding variants do not contribute to
      low levels of high-density lipoprotein cholesterol.
AB  - BACKGROUND: Niemann-Pick disease type A and B is caused by a deficiency of acid
      sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase-1
      (SMPD1) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be
      associated with a severe reduction in plasma high-density lipoprotein (HDL)
      cholesterol. METHODS: Two common coding polymorphisms in the SMPD1 gene, the
      G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide
      region, were investigated in 118 unrelated subjects of French Canadian descent
      with low plasma levels of HDL-cholesterol (< 5th percentile for age and gender
      matched subjects). Control subjects (n = 230) had an HDL-cholesterol level > the
      25th percentile. RESULTS: For G1522A the frequency of the G and A alleles were
      75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects
      with low HDL-cholesterol (p = 0.317). The frequency of 6 and 7 hexanucleotide
      repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1%
      in subjects with low HDL-cholesterol (p = 0.619). Ten different haplotypes were
      observed in cases and controls. Overall haplotype frequencies in cases and
      controls were not significantly different. CONCLUSION: These results suggest that
      the two common coding variants at the SMPD1 gene locus are not associated with
      low HDL-cholesterol levels in the French Canadian population.

PMID- 18088426
TI  - Identification of a human immunodominant B-cell epitope within the immunoglobulin
      A1 protease of Streptococcus pneumoniae.
AB  - BACKGROUND: The IgA1 protease of Streptococcus pneumoniae is a proteolytic enzyme
      that specifically cleaves the hinge regions of human IgA1, which dominates most
      mucosal surfaces and is the major IgA isotype in serum. This protease is
      expressed in all of the known pneumococcal strains and plays a major role in
      pathogen's resistance to the host immune response. The present work was focused
      at identifying the immunodominant regions of pneumococcal IgA1 protease
      recognized by the human antibody response. RESULTS: An antigenic sequence
      corresponding to amino acids 420-457 (epiA) of the iga gene product was
      identified by screening a pneumococcal phage display library with patients' sera.
      The epiA peptide is conserved in all pneumococci and in two out of three S. mitis
      strains, while it is not present in other oral streptococci so far sequenced.
      This epitope was specifically recognized by antibodies present in sera from 90%
      of healthy adults, thus representing an important target of the humoral response
      to S. pneumoniae and S. mitis infection. Moreover, sera from 68% of children less
      than 4 years old reacted with the epiA peptide, indicating that the human immune
      response against streptococcal antigens occurs during childhood. CONCLUSION: The
      broad and specific recognition of the epiA polypeptide by human sera demonstrate
      that the pneumococcal IgA1 protease contains an immunodominant B-cell epitope.
      The use of phage display libraries to identify microbe or disease-specific
      antigens recognized by human sera is a valuable approach to epitope discovery.

PMID- 18088427
TI  - Lung inflammation following a single exposure to swine barn air.
AB  - BACKGROUND: Exposure to swine barn air is an occupational hazard. Barn workers
      following an eight-hour work shift develop many signs of lung dysfunction
      including lung inflammation. However, the in situ cellular and molecular
      mechanisms responsible for lung dysfunction induced following exposure to the
      barn air remain largely unknown. Specifically, the recruitment and role of
      pulmonary intravascular monocytes/macrophages (PIMMs), which increase host
      susceptibility for acute lung inflammation, remain unknown in barn air induced
      lung inflammation. We hypothesized that barn exposure induces recruitment of
      PIMMs and increases susceptibility for acute lung inflammation with a secondary
      challenge. METHODS: Sprague-Dawley rats were exposed either to the barn or
      ambient air for eight hours and were euthanized at various time intervals to
      collect blood, broncho-alveolar lavage fluid (BALF) and lung tissue.
      Subsequently, following an eight hour barn or ambient air exposure, rats were
      challenged either with Escherichia coli (E. coli) lipopolysaccharide (LPS) or
      saline and euthanized 6 hours post-LPS or saline treatment. We used ANOVA (P <
      0.05 means significant) to compare group differences. RESULTS: An eight-hour
      exposure to barn air induced acute lung inflammation with recruitment of
      granulocytes and PIMMs. Granulocyte and PIMM numbers peaked at one and 48 hour
      post-exposure, respectively.Secondary challenge with E. coli LPS at 48 hour
      following barn exposure resulted in intense lung inflammation, greater numbers of
      granulocytes, increased number of cells positive for TNF-alpha and decreased
      amounts of TGF-beta2 in lung tissues. We also localized TNF-alpha, IL-1beta and
      TGF-beta2 in PIMMs. CONCLUSION: A single exposure to barn air induces lung
      inflammation with recruitment of PIMMs and granulocytes. Recruited PIMMs may be
      linked to more robust lung inflammation in barn-exposed rats exposed to LPS.
      These data may have implications of workers exposed to the barn air who may
      encounter secondary microbial challenge.

PMID- 18088428
TI  - Diversity in conserved genes in tomato.
AB  - BACKGROUND: Tomato has excellent genetic and genomic resources including a broad
      set of Expressed Sequence Tag (EST) data and high-density genetic maps. In
      addition, emerging physical maps and bacterial artificial clone sequence data
      serve as template to investigate genetic variation within the cultivated
      germplasm pool with the goal to manipulate agriculturally important traits.
      Unfortunately, the nearly exclusive focus of resource development on
      interspecific populations for genetic analyses and diversity studies has left a
      void in our understanding of genotypic variation within tomato breeding programs
      that focus on intra-specific populations. We describe the results of a study to
      identify nucleotide variation within tomato breeding germplasm and mapping
      parents for a set of conserved single-copy ESTs that are orthologous between
      tomato and Arabidopsis. RESULTS: Using a pooled sequencing strategy, 967 tomato
      transcripts were screened for polymorphism in 12 tomato lines. Although intron
      position was conserved, intron lengths were 2-fold larger in tomato than in
      Arabidopsis. A total of 1,487 single nucleotide polymorphisms and 282
      insertion/deletions were identified, of which 579 and 206 were polymorphic in
      breeding germplasm, respectively. Fresh market and processing germplasm were
      clearly divergent, as were Solanum lycopersicum var. cerasiformae and Solanum
      pimpinellifolium, tomato's closest relatives. The polymorphisms identified serve
      as marker resources for tomato. The COS is also applicable to other Solanaceae
      crops. CONCLUSIONS: The results from this research enabled significant progress
      towards bridging the gap between genetic and genomic resources developed for
      populations derived from wide crosses and those applicable to intra-specific
      crosses for breeding in tomato.

PMID- 18088429
TI  - Microarray-based method for detection of unknown genetic modifications.
AB  - BACKGROUND: Due to the increased use of genetic modifications in crop
      improvement, there is a need to develop effective methods for the detection of
      both known and unknown transgene constructs in plants. We have developed a
      strategy for detection and characterization of unknown genetic modifications and
      we present a proof of concept for this method using Arabidopsis thaliana and
      Oryza sativa (rice). The approach relies on direct hybridization of total genomic
      DNA to high density microarrays designed to have probes tiled throughout a set of
      reference sequences. RESULTS: We show that by using arrays with 25 basepair
      probes covering both strands of a set of 235 vectors (2 million basepairs) we can
      detect transgene sequences in transformed lines of A. thaliana and rice without
      prior knowledge about the transformation vectors or the T-DNA constructs used to
      generate the studied plants. CONCLUSION: The approach should allow the user to
      detect the presence of transgene sequences and get sufficient information for
      further characterization of unknown genetic constructs in plants. The only
      requirements are access to a small amount of pure transgene plant material, that
      the genetic construct in question is above a certain size (here >/= 140
      basepairs) and that parts of the construct shows some degree of sequence
      similarity with published genetic elements.

PMID- 18088430
TI  - Genetic characterization of psp encoding the DING protein in Pseudomonas
      fluorescens SBW25.
AB  - BACKGROUND: DING proteins constitute a conserved and broadly distributed set of
      proteins found in bacteria, fungi, plants and animals (including humans).
      Characterization of DING proteins from animal and plant tissues indicated ligand
      binding ability suggesting a role for DING proteins in cell signaling and
      biomineralization. Surprisingly, the genes encoding DING proteins in eukaryotes
      have not been identified in the eukaryotic genome or EST databases. Recent
      discovery of a DING homologue (named Psp here) in the genome of Pseudomonas
      fluorescens SBW25 provided a unique opportunity to investigate the physiological
      roles of DING proteins. P. fluorescens SBW25 is a model bacterium that can
      efficiently colonize plant surfaces and enhance plant health. In this report we
      genetically characterize Psp with a focus on conditions under which psp is
      expressed and the protein exported. RESULTS: Psp is closely related to the
      periplasmic Pi binding component of the ABC-type phosphate transporter system
      (Pst). psp is flanked by a gene cluster predicted to function as a type II
      protein secretion system (Hxc). Deletion analysis combined with chromosomally
      integrated 'lacZ fusions showed that both psp and pstC are induced by Pi
      limitation and that pstC is required for competitive growth of the bacterium in
      Pi limited medium. hxcR is not regulated by Pi limitation. Psp was detected
      (using anti-DING serum) in the supernatant of wild-type culture but was greatly
      reduced in the supernatant of an isogenic strain carrying an hxcR mutation
      (DeltahxcR). A promoter fusion between hxcR and a promoterless copy of a gene
      ('dapB) essential for growth in the plant environment showed that expression of
      hxcR is elevated during colonization of sugar beet seedlings. A similar analysis
      of psp showed that it is not induced in the plant environment. CONCLUSION: Psp
      gene is expressed under conditions of Pi limitation. It is an exoprotein secreted
      mainly via the Hxc type II secretion system, whose expression is elevated on
      plant surfaces. We propose that Psp is involved in extracellular scavenging of
      phosphates, which are subsequently taken up by the cell-bound Pst transport
      system.

PMID- 18088431
TI  - Ab initio identification of human microRNAs based on structure motifs.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNA molecules that are
      directly involved in post-transcriptional regulation of gene expression. The
      mature miRNA sequence binds to more or less specific target sites on the mRNA.
      Both their small size and sequence specificity make the detection of completely
      new miRNAs a challenging task. This cannot be based on sequence information
      alone, but requires structure information about the miRNA precursor. Unlike
      comparative genomics approaches, ab initio approaches are able to discover
      species-specific miRNAs without known sequence homology. RESULTS: MiRPred is a
      novel method for ab initio prediction of miRNAs by genome scanning that only
      relies on (predicted) secondary structure to distinguish miRNA precursors from
      other similar-sized segments of the human genome. We apply a machine learning
      technique, called linear genetic programming, to develop special classifier
      programs which include multiple regular expressions (motifs) matched against the
      secondary structure sequence. Special attention is paid to scanning issues. The
      classifiers are trained on fixed-length sequences as these occur when shifting a
      window in regular steps over a genome region. Various statistical and empirical
      evidence is collected to validate the correctness of and increase confidence in
      the predicted structures. Among other things, we propose a new criterion to
      select miRNA candidates with a higher stability of folding that is based on the
      number of matching windows around their genome location. An ensemble of 16 motif
      based classifiers achieves 99.9 percent specificity with sensitivity remaining on
      an acceptable high level when requiring all classifiers to agree on a positive
      decision. A low false positive rate is considered more important than a low false
      negative rate, when searching larger genome regions for unknown miRNAs. 117 new
      miRNAs have been predicted close to known miRNAs on human chromosome 19. All
      candidate structures match the free energy distribution of miRNA precursors which
      is significantly shifted towards lower free energies. We employed a human EST
      library and found that around 75 percent of the candidate sequences are likely to
      be transcribed, with around 35 percent located in introns. CONCLUSION: Our motif
      finding method is at least competitive to state-of-the-art feature-based methods
      for ab initio miRNA discovery. In doing so, it requires less previous knowledge
      about miRNA precursor structures while programs and motifs allow a more
      straightforward interpretation and extraction of the acquired knowledge.

PMID- 18088432
TI  - Risk factors for ischaemic heart disease in a Cretan rural population: a twelve
      year follow-up study.
AB  - BACKGROUND: Crete has been of great epidemiological interest ever since the
      publication of the Seven Countries Study. In 1988 a well-defined area of rural
      Crete was studied, with only scarce signs of coronary heart disease (CHD) despite
      the unfavorable risk profile. The same population was re-examined twelve years
      later aiming to describe the trends of CHD risk factors over time and discuss
      some key points on the natural course of coronary heart disease in a rural
      population of Crete. METHODS AND RESULTS: We re-examined 200 subjects (80.7% of
      those still living in the area, 62.4 +/- 17.0 years old). The prevalence of risk
      factors for CHD was high with 65.9% of men and 65.1% of women being hypertensive,
      14.3% of men and 16.5% of women being diabetic, 44% of men being active smokers
      and more than 40% of both sexes having hyperlipidaemia. Accordingly, 77.5% of the
      population had a calculated Framingham Risk Score (FRS) > or = 15%, significantly
      higher compared to baseline (p < 0.001). The overall occurrence rate for CHD
      events was calculated at 7.1 per 1000 person-years (95% confidence interval: 6.8
      7.3). CONCLUSION: The study confirms the unfavorable risk factor profile of a
      well defined rural population in Crete. Its actual effect on the observed
      incidence of coronary events in Cretans remains yet to be defined.

PMID- 18088433
TI  - Lifestyle variables and the risk of myocardial infarction in the general practice
      research database.
AB  - BACKGROUND: The primary objective of this study is to estimate the association
      between body mass index (BMI) and the risk of first acute myocardial infarction
      (AMI). As a secondary objective, we considered the association between other
      lifestyle variables, smoking and heavy alcohol use, and AMI risk. METHODS: This
      study was conducted in the general practice research database (GPRD) which is a
      database based on general practitioner records and is a representative sample of
      the United Kingdom population. We matched cases of first AMI as identified by
      diagnostic codes with up to 10 controls between January 1st, 2001 and December
      31st, 2005 using incidence density sampling. We used multiple imputation to
      account for missing data. RESULTS: We identified 19,353 cases of first AMI which
      were matched on index date, GPRD practice and age to 192,821 controls. There was
      a modest amount of missing data in the database, and the patients with missing
      data had different risks than those with recorded values. We adjusted our
      analysis for each lifestyle variable jointly and also for age, sex, and number of
      hospitalizations in the past year. Although a record of underweight (BMI <18.0
      kg/m2) did not alter the risk for AMI (adjusted odds ratio (OR): 1.00; 95%
      confidence interval (CI): 0.87-1.11) when compared with normal BMI (18.0-24.9
      kg/m2), obesity (BMI > or =30 kg/m2) predicted an increased risk (adjusted OR:
      1.41; 95% CI: 1.35-1.47). A history of smoking also predicted an increased risk
      of AMI (adjusted OR: 1.81; 95% CI: 1.75-1.87) as did heavy alcohol use (adjusted
      OR: 1.15; 95% CI: 1.06-1.26). CONCLUSION: This study illustrates that obesity,
      smoking and heavy alcohol use, as recorded during routine care by a general
      practitioner, are important predictors of an increased risk of a first AMI. In
      contrast, low BMI does not increase the risk of a first AMI.

PMID- 18088434
TI  - Measuring and decomposing inequity in self-reported morbidity and self-assessed
      health in Thailand.
AB  - BACKGROUND: In recent years, interest in the study of inequalities in health has
      not stopped at quantifying their magnitude; explaining the sources of
      inequalities has also become of great importance. This paper measures
      socioeconomic inequalities in self-reported morbidity and self-assessed health in
      Thailand, and the contributions of different population subgroups to those
      inequalities. METHODS: The Health and Welfare Survey 2003 conducted by the Thai
      National Statistical Office with 37,202 adult respondents is used for the
      analysis. The health outcomes of interest derive from three self-reported
      morbidity and two self-assessed health questions. Socioeconomic status is
      measured by adult-equivalent monthly income per household member. The
      concentration index (CI) of ill health is used as a measure of socioeconomic
      health inequalities, and is subsequently decomposed into contributing factors.
      RESULTS: The CIs reveal inequality gradients disadvantageous to the poor for both
      self-reported morbidity and self-assessed health in Thailand. The magnitudes of
      these inequalities were higher for the self-assessed health outcomes than for the
      self-reported morbidity outcomes. Age and sex played significant roles in
      accounting for the inequality in reported chronic illness (33.7 percent of the
      total inequality observed), hospital admission (27.8 percent), and self-assessed
      deterioration of health compared to a year ago (31.9 percent). The effect of
      being female and aged 60 years or older was by far the strongest demographic
      determinant of inequality across all five types of health outcome. Having a low
      socioeconomic status as measured by income quintile, education and work status
      were the main contributors disadvantaging the poor in self-rated health compared
      to a year ago (47.1 percent) and self-assessed health compared to peers (47.4
      percent). Residence in the rural Northeast and rural North were the main regional
      contributors to inequality in self-reported recent and chronic illness, while
      residence in the rural Northeast was the major contributor to the tendency of the
      poor to report lower levels of self-assessed health compared to peers.
      CONCLUSION: The findings confirm that substantial socioeconomic inequalities in
      health as measured by self-reported morbidity and self-assessed health exist in
      Thailand. Decomposition analysis shows that inequalities in health status are
      associated with particular demographic, socioeconomic and geographic population
      subgroups. Vulnerable subgroups which are prone to both ill health and relative
      poverty warrant targeted policy attention.

PMID- 18088435
TI  - Use of complementary alternative medicine for low back pain consulting in general
      practice: a cohort study.
AB  - BACKGROUND: Although back pain is considered one of the most frequent reasons why
      patients seek complementary and alternative medical (CAM) therapies little is
      known on the extent patients are actually using CAM for back pain. METHODS: This
      is a post hoc analysis of a longitudinal prospective cohort study embedded in a
      RCT. General practitioners (GPs) recruited consecutively adult patients
      presenting with LBP. Data on physical function, on subjective mood, and on
      utilization of health services was collected at the first consultation and at
      follow-up telephone interviews for a period of twelve months RESULTS: A total of
      691 (51%) respectively 928 (69%) out of 1,342 patients received one form of CAM
      depending on the definition. Local heat, massage, and spinal manipulation were
      the forms of CAM most commonly offered. Using CAM was associated with specialist
      care, chronic LBP and treatment in a rehabilitation facility. Receiving spinal
      manipulation, acupuncture or TENS was associated with consulting a GP providing
      these services. Apart from chronicity disease related factors like functional
      capacity or pain only showed weak or no association with receiving CAM.
      CONCLUSION: The frequent use of CAM for LBP demonstrates that CAM is popular in
      patients and doctors alike. The observed association with a treatment in a
      rehabilitation facility or with specialist consultations rather reflects
      professional preferences of the physicians than a clear medical indication. The
      observed dependence on providers and provider related services, as well as a
      significant proportion receiving CAM that did not meet the so far established
      selection criteria suggests some arbitrary use of CAM.

PMID- 18088436
TI  - Multi-modal-analgesia for pain management after Hallux Valgus surgery: a
      prospective randomised study on the effect of ankle block.
AB  - BACKGROUND: Pain and emesis are the two major complaints after day case surgery.
      Local anaesthesia has become an important part of optimizing intra and post
      operative pain treatment, but is sometimes not entirely sufficient. The aim of
      the present study was to study the effect of adding an ankle block to a multi
      modal analgesic approach on the first 24-hour-need for rescue analgesia in
      patients undergoing elective Hallux Valgus surgery. TYPE OF STUDY: Prospective,
      randomized patient-blind study comparing ankle block with levo-bupivacaine,
      lidocaine and Saline placebo control. METHODS: Ninety patients were studied
      comparing ankle block (15 cc) using levo-bupivacaine 2.5 mg/ml, lidocaine 10
      mg/ml or placebo (saline) on day-case elective Hallux Valgus surgery, supported
      by general anaesthesia in all cases. Primary study endpoint was number of
      patient's requiring oral analgesics during the first 24 post-operative hours.
      RESULTS: Ankle block had no effect on need for rescue analgesia and pain ratings
      during the 1st 24 postoperative hours, there was no difference seen between
      placebo and any of the two active local anaesthesia studied. The only differences
      seen was that both lidocaine and levo-bupivacaine reduced the intra-operative
      need for anaesthetic (sevoflurane) and that levo-bupivacaine patients had a lower
      need as compared to the lidocaine patients for oral analgesics during the
      afternoon of surgery. CONCLUSION: Adding a single shot ankle block to a multi
      modal pain management strategy reduces the need for intra-operative anaesthesia
      but has no major impact of need of rescue analgesics or pain during the first 24
      hour after surgery.

PMID- 18088437
TI  - The reach and impact of social marketing and reproductive health communication
      campaigns in Zambia.
AB  - BACKGROUND: Like many sub-Saharan African countries, Zambia is dealing with major
      health issues, including HIV/AIDS, family planning, and reproductive health. To
      address reproductive health problems and the HIV/AIDS epidemic in Zambia, several
      social marketing and health communication programs focusing on reproductive and
      HIV/AIDS prevention programs are being implemented. This paper describes the
      reach of these programs and assesses their impact on condom use. METHODS: This
      paper assesses the reach of selected radio and television programs about family
      planning and HIV/AIDS and of communications about the socially marketed Maximum
      condoms in Zambia, as well as their impact on condom use, using data from the
      2001-2002 Zambia Demographic and Health Survey. To control for self-selection and
      endogeneity, we use a two-stage regression model to estimate the effect of
      program exposure on the behavioural outcomes. RESULTS: Those who were exposed to
      radio and television programs about family planning and HIV/AIDS were more likely
      to have ever used a condom (OR = 1.16 for men and 1.06 for women). Men highly
      exposed to Maximum condoms social marketing communication were more likely than
      those with low exposure to the program to have ever used a condom (OR = 1.48),
      and to have used a condom at their last sexual intercourse (OR = 1.23).
      CONCLUSION: Findings suggest that the reproductive health and social marketing
      campaigns in Zambia reached a large portion of the population and had a
      significant impact on condom use. The results suggest that future reproductive
      health communication campaigns that invest in radio programming may be more
      effective than those investing in television programming, and that future
      campaigns should seek to increase their impact among women, perhaps by focusing
      on the specific constrains that prevent females from using condoms.

PMID- 18088438
TI  - The Personal Sequence Database: a suite of tools to create and maintain web
      accessible sequence databases.
AB  - BACKGROUND: Large molecular sequence databases are fundamental resources for
      modern bioscientists. Whether for project-specific purposes or sharing data with
      colleagues, it is often advantageous to maintain smaller sequence databases.
      However, this is usually not an easy task for the average bench scientist.
      RESULTS: We present the Personal Sequence Database (PSD), a suite of tools to
      create and maintain small- to medium-sized web-accessible sequence databases. All
      interactions with PSD tools occur via the internet with a web browser. Users may
      define sequence groups within their database that can be maintained privately or
      published to the web for public use. A sequence group can be downloaded, browsed,
      searched by keyword or searched for sequence similarities using BLAST. Publishing
      a sequence group extends these capabilities to colleagues and collaborators. In
      addition to being able to manage their own sequence databases, users can enroll
      sequences in BLASTAgent, a BLAST hit tracking system, to monitor NCBI databases
      for new entries displaying a specified level of nucleotide or amino acid
      similarity. CONCLUSION: The PSD offers a valuable set of resources unavailable
      elsewhere. In addition to managing sequence data and BLAST search results, it
      facilitates data sharing with colleagues, collaborators and public users. The PSD
      is hosted by the authors and is available at
      http://bioinfo.cgrb.oregonstate.edu/psd/.

PMID- 18088440
TI  - Oxidative stress as a risk factor for osteoporosis in elderly Mexicans as
      characterized by antioxidant enzymes.
AB  - BACKGROUND: Oxidative stress (OxS) has recently been linked with osteoporosis;
      however, we do not know the influence of OxS as an independent risk factor for
      this disease. METHODS: We conducted a case-control study in 94 subjects > or =60
      years of age, 50 healthy and 44 with osteoporosis. We measured total antioxidant
      status, plasma lipid peroxides, antioxidant activity of superoxide dismutase and
      glutathione peroxidase (GPx), and calculated the SOD/GPx ratio. Bone mineral
      density was obtained at the peripheral DXA in calcaneus using a portable Norland
      Apollo Densitometer. Osteoporosis was considered when subjects had a BMD of 2.5
      standard deviations or more below the mean value for young adults. RESULTS: GPx
      antioxidant activity was significantly lower in the group of subjects with
      osteoporosis in comparison with the group of healthy subjects (p < 0.01); in
      addition, the SOD/GPx ratio was significantly higher in the group of individuals
      with osteoporosis (p < 0.05). In logistic regression analysis, we found OxS to be
      an independent risk factor for osteoporosis (odds ratio [OR] = 2.79; 95%
      confidence interval [95% CI] = 1.08-7.23; p = 0.034). CONCLUSION: Our findings
      suggest that OxS is an independent risk factor for osteoporosis linked to
      increase of SOD/GPx ratio.

PMID- 18088442
TI  - Synthesis of crispine A analogues via an intramolecular Schmidt reaction.
AB  - An intramolecular Schmidt reaction strategy for the synthesis of various
      derivatives of crispine A using azido-ketone as a key intermediate is described.

PMID- 18088441
TI  - Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic
      transmission through primary afferents.
AB  - BACKGROUND: We have proposed that nerve injury-specific loss of spinal tonic
      cholinergic inhibition may play a role in the analgesic effects of nicotinic
      acetylcholine receptor (nAChR) agonists on neuropathic pain. However, the tonic
      cholinergic inhibition of pain remains to be well characterized. RESULTS: Here,
      we show that choline acetyltransferase (ChAT) signals were localized not only in
      outer dorsal horn fibers (lamina I-III) and motor neurons in the spinal cord, but
      also in the vast majority of neurons in the dorsal root ganglion (DRG). When mice
      were treated with an antisense oligodeoxynucleotide (AS-ODN) against ChAT, which
      decreased ChAT signals in the dorsal horn and DRG, but not in motor neurons, they
      showed a significant decrease in nociceptive thresholds in paw pressure and
      thermal paw withdrawal tests. Furthermore, in a novel electrical stimulation
      induced paw withdrawal (EPW) test, the thresholds for stimulation through C-,
      Adelta- and Abeta-fibers were all decreased by AS-ODN-pretreatments. The
      administration of nicotine (10 nmol i.t.) induced a recovery of the nociceptive
      thresholds, decreased by the AS-ODN, in the mechanical, thermal and EPW tests.
      However, nicotine had no effects in control mice or treated with a mismatch
      scramble (MS)-ODN in all of these nociception tests. CONCLUSION: These findings
      suggest that primary afferent cholinergic neurons produce tonic inhibition of
      spinal pain through nAChR activation, and that intrathecal administration of
      nicotine rescues the loss of tonic cholinergic inhibition.

PMID- 18088443
TI  - Analysis of agreement among definitions of metabolic syndrome in nondiabetic
      Turkish adults: a methodological study.
AB  - BACKGROUND: We aimed to explore the agreement among World Health Organization
      (WHO), European Group for the Study of Insulin Resistance (EGIR), National
      Cholesterol Education Program (NCEP), American College of Endocrinology (ACE),
      and International Diabetes Federation (IDF) definitions of the metabolic
      syndrome. METHODS: 1568 subjects (532 men, 1036 women, mean age 45 and standard
      deviation (SD) 13 years) were evaluated in this cross-sectional, methodological
      study. Cardiometabolic risk factors were determined. Insulin sensitivity was
      calculated by HOMA-IR. Agreement among definitions was determined by the kappa
      statistic. ANOVA and post hoc Tukey's test were used to compare multiple groups.
      RESULTS: The agreement between WHO and EGIR definitions was very good (kappa:
      0.83). The agreement between NCEP, ACE, and IDF definitions was substantial to
      very good (kappa: 0.77-0.84). The agreement between NCEP or ACE or IDF and WHO or
      EGIR definitions was fair (kappa: 0.32-0.37). The age and sex adjusted prevalence
      of metabolic syndrome was 38% by NCEP, 42% by ACE and IDF, 20% by EGIR and 19% by
      WHO definition. The evaluated definitions were dichotomized after analysis of
      design, agreement and prevalence: insulin measurement requiring definitions (WHO
      and EGIR) and definitions not requiring insulin measurement (NCEP, ACE, IDF). One
      definition was selected from each set for comparison. WHO-defined subjects were
      more insulin resistant than subjects without the metabolic syndrome (mean and SD
      for log HOMA-IR, 0.53 +/- 0.14 vs. 0.07 +/- 0.23, respectively, p < 0.05) and had
      higher Framingham risk scores (mean and SD, 2.99 +/- 4.64% vs. 1.10 +/- 1.87%,
      respectively, p < 0.05). The additional subjects identified by IDF definition,
      but not by WHO definition also had more insulin resistance and higher Framingham
      risk scores than subjects without the metabolic syndrome (mean and SD, log HOMA
      IR 0.18 +/- 0.18 vs. 0.07 +/- 0.23, p < 0.05 and Framingham risk score 2.93 +/-
      4.54% vs. 1.10 +/- 1.87%, p < 0.05). The IDF-identified additional subjects had
      similar Framingham risk scores as WHO-identified subjects (p > 0.05), but lower
      log HOMA-IR values (p < 0.05). CONCLUSION: The metabolic syndrome definitions
      that do not require measurement of insulin levels (NCEP, ACE and IDF) identify
      twice more patients with insulin resistance and increased Framingham risk scores
      and are more useful than the definitions that require measurement of insulin
      levels (WHO and EGIR).

PMID- 18088444
TI  - Virulence factors in brucellosis: implications for aetiopathogenesis and
      treatment.
AB  - Brucella species are responsible for the global zoonotic disease brucellosis.
      These intracellular pathogens express a set of factors - including
      lipopolysaccharides, virulence regulator proteins and phosphatidylcholine - to
      ensure their full virulence. Some virulence factors are essential for invasion of
      the host cell, whereas others are crucial to avoid elimination by the host. They
      allow Brucella spp. to survive and proliferate within its replicative vacuole and
      enable the bacteria to escape detection by the host immune system. Several
      strategies have been used to develop animal vaccines against brucellosis, but no
      adequate vaccine yet exists to cure the disease in humans. This is probably due
      to the complicated pathophysiology of human Brucella spp. infection, which is
      different than in animal models. Here we review Brucella spp. virulence factors
      and how they control bacterial trafficking within the host cell.

PMID- 18088439
TI  - Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on
      early gene expression for glial and neural-related molecules in central nervous
      system mixed glial cell cultures: neurotrophins, growth factors and structural
      proteins.
AB  - BACKGROUND: In multiple sclerosis, inflammatory cells are found in both active
      and chronic lesions, and it is increasingly clear that cytokines are involved
      directly and indirectly in both formation and inhibition of lesions. We propose
      that cytokine mixtures typical of Th1 or Th2 lymphocytes, or monocyte/macrophages
      each induce unique molecular changes in glial cells. METHODS: To examine changes
      in gene expression that might occur in glial cells exposed to the secreted
      products of immune cells, we have used gene array analysis to assess the early
      effects of different cytokine mixtures on mixed CNS glia in culture. We compared
      the effects of cytokines typical of Th1 and Th2 lymphocytes and
      monocyte/macrophages (M/M) on CNS glia after 6 hours of treatment. RESULTS: In
      this paper we focus on changes with potential relevance for neuroprotection and
      axon/glial interactions. Each mixture of cytokines induced a unique pattern of
      changes in genes for neurotrophins, growth and maturation factors and related
      receptors; most notably an alternatively spliced form of trkC was markedly
      downregulated by Th1 and M/M cytokines, while Th2 cytokines upregulated BDNF.
      Genes for molecules of potential importance in axon/glial interactions, including
      cell adhesion molecules, connexins, and some molecules traditionally associated
      with neurons showed significant changes, while no genes for myelin-associated
      genes were regulated at this early time point. Unexpectedly, changes occurred in
      several genes for proteins initially associated with retina, cancer or bone
      development, and not previously reported in glial cells. CONCLUSION: Each of the
      three cytokine mixtures induced specific changes in gene expression that could be
      altered by pharmacologic strategies to promote protection of the central nervous
      system.

PMID- 18088445
TI  - The efficacy and neurotoxicity of dexmedetomidine administered via the epidural
      route.
AB  - BACKGROUND: alpha(2)-Adrenoceptor agonists administered into the intrathecal and
      epidural space have been found to be effective in the treatment of chronic pain.
      Moreover, it was shown that they increase the analgesic effects of local
      anaesthetics and provide sedation, anxiolysis and haemodynamic stability.
      Dexmedetomidine, a potent and highly selective alpha(2)-adrenoceptor agonist, is
      in current clinical use, particularly in the intensive care unit. Our aim was to
      investigate whether dexmedetomidine produced motor and sensory blockade and
      neurotoxic effects when administrated via the epidural catheter in rabbits.
      METHODS: Twenty-one New Zealand white rabbits were included in the study. Animals
      were randomized into three groups. In Group L: lidocaine (2%), in Group LD:
      lidocaine (2%) + dexmedetomidine (5 microg) and in Group D: dexmedetomidine (10
      microg) were administered by epidural catheter. Motor and sensory blockade were
      evaluated. After the evaluation of block, the animals were euthanized and their
      spinal cords removed for neuropathological evaluations. RESULTS: Motor and
      sensory blockade were lower in Group D than in Group L and Group LD (P < 0.01).
      Although there were no differences between the groups for ischaemia of the
      medulla spinalis, evidence of demyelinization of the oligodendrocytes in the
      white matter in Group D was significantly higher than in Group L (P = 0.035).
      CONCLUSIONS: We observed that dexmedetomidine does not have motor and sensory
      effects, but it may have a harmful effect on the myelin sheath when administered
      via the epidural route.

PMID- 18088446
TI  - The humanitarian emergency in Burundi: evaluation of the operational strategy for
      management of nutritional crisis.
AB  - OBJECTIVE: To evaluate the impact and appropriateness of programmes for the
      management and treatment of severe malnutrition in emergency situations. DESIGN:
      A central unified database was set up with all data and statistics provided by
      nutritional centres (NC) active in Burundi. SETTING: The paper describes the case
      of Burundi as an example of the response of the humanitarian community to
      nutritional crisis. SUBJECTS: Since 1999, more than one million (1,054,210)
      severely malnourished patients were treated in NC established in Burundi.
      RESULTS: Peaks of beneficiaries were registered in 2000 and 2001; the admission
      rate started to decrease in 2002. In 2004, twenty therapeutic feeding centres
      (TFC) and 224 supplementary feeding centres (SFC) were active for the treatment
      of 127,420 beneficiaries. Nutritional programmes were present in every province
      with a coverage rate of 55%. The most convincing impact of the nutritional
      programme in Burundi was the reduction of mortality rate in children under 5
      years of age; an impact on the prevalence of acute malnutrition could not be
      demonstrated. Children under 5 years old accounted for 62% of beneficiaries in
      TFC and 76% in SFC. TFC performance indicators fulfilled the minimum standards in
      disaster response; the performance of SFC was not so optimal with a low recovery
      rate (69% v. >80%) and a high non-respondent rate (16% v. <5%). With the
      combination of coverage and cure rate, the programme met 44% of the assessed
      needs in 2004. CONCLUSIONS: In Burundi the stabilisation of security conditions
      permitted a combination of humanitarian responses ranging from emergency
      activities to strengthening of community-based initiatives that could correct the
      coverage and impact limitations.

PMID- 18088447
TI  - Lipid profile in men and women with different levels of sports participation and
      physical activity.
AB  - OBJECTIVE: The purpose of the present study was to analyse the lipid profile in
      men and women differentiated according to energy expenditure during sports
      participation (EE(SPORT)), energy expenditure during active leisure time
      (EE(ALT)) and overall energy expenditure (EE(TOTAL)). DESIGN: The subjects were
      grouped by sex, age, EE(SPORT), EE(ALT) and EE(TOTAL). Group differences were
      analysed using analyses of covariance with BMI and alcohol consumption as
      covariates. SETTING: Physical activity was assessed using the Flemish Physical
      Activity Computerised Questionnaire. Fasting blood samples were taken to measure
      total cholesterol (TC), TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and
      the ratio TC:HDL-C. SUBJECTS: The study sample consisted of 1170 Flemish men and
      women between 18 and 75 years of age. RESULTS: Differences in lipid profile were
      observed in the younger age group (<45 years), all in favour of the most active
      group. More specifically, when differentiating by EE(ALT) and EE(TOTAL), men had
      a healthier lipid profile for TAG, HDL-C and TC:HDL-C. Differentiation according
      to EE(SPORT) revealed the same significant results except for TAG. In women
      significant results for HDL-C, LDL-C and TC:HDL-C were found when differentiated
      by EE(SPORT). CONCLUSIONS: Men and women <45 years of age with higher levels of
      energy expenditure due to sport show a better lipid profile than their sedentary
      counterparts. When differentiating subjects according to energy expenditure
      during active leisure time or overall energy expenditure, only in men was a
      healthier lipid profile observed in favour of the most active subjects.

PMID- 18088448
TI  - Public health and economic costs of investigating a suspected outbreak of
      Legionnaires' disease.
AB  - This paper provides one of the first assessments of the burden of both the public
      health investigation and the economic costs associated with an apparent outbreak
      of Legionnaires' disease (LD) in South East London. In addition to
      epidemiological, microbiological and environmental investigations, we collected
      data on the staff time and resources committed by the 11 main organizations
      responsible for managing the outbreak. Of the overall estimated costs of 455,856
      pounds, only 14% (64,264 pounds) was spent on investigation and control of the
      outbreak compared with 86% (391,592 pounds) spent on the hospital treatment of
      the patients. The time and money spent on public health services in this
      investigation appear to represent good value for money considering the potential
      costs of a major outbreak, including the high case-fatality rate in LD generally
      and the high health-care costs. Further research is needed to determine optimum
      strategies for the cost-effective use of health system resources in
      investigations of LD. Whether the threshold for investigation of cases should be
      based on observed incidence rates or the cost-effectiveness of investigations, or
      both, should be debated further.

PMID- 18088449
TI  - Gender inequality increases women's risk of hiv infection in Moshi, Tanzania.
AB  - This study examined the hypothesis that multiple dimensions of gender inequality
      increase women's risk for HIV infection using a population-based survey of 1418
      women aged 20 to 44 in Moshi, Tanzania. Three forms of HIV exposures were
      assessed reflecting gender power imbalance: economic exposures (age difference
      between partners and partner's contributions to children's expenses), physical
      exposures (coerced first sex and intimate partner violence) and social exposures
      (ever had problems conceiving). Behavioural risk factors included number of
      sexual partners for women in the last three years, partner had other wives or
      girlfriends, non-use of condom and alcohol use at least once a week in the last
      12 months. Multivariate logistic regression analysis showed that a woman had a
      significantly elevated risk for HIV if she had a partner more than 10 years older
      (OR=2.5), her partner made low financial contributions to children's expenses
      (OR=1.7), or she experienced coerced first sex before age 18 years (OR=2.0) even
      after taking into account the effects of risk behaviour factors. The association
      between ever had problem conceiving and HIV infection was explained away by risk
      behaviour factors. The findings lend support to the hypothesis that economic
      deprivation and experience of sexual violence increase women's vulnerability to
      HIV, providing further evidence for extending the behavioural approach to HIV
      interventions to incorporate women's economic empowerment, elimination of gender
      based violence and promotion of changing attitudes and behaviours among men.

PMID- 18088450
TI  - Traditional occupations and nutritional adaptation among Central Indian caste
      populations.
AB  - The socioeconomic milieu has benefits and drawbacks for determining level of
      nutrition. The Indian population provides an excellent example of nutrition
      driven adaptation. The present paper deals with the relationship between BMI
      (body mass index) and traditional occupation and process of adaptation among
      adult males of Central India. Anthropometric data collected by the
      Anthropological Survey of India on stature, sitting height and weight of 6663
      adult males belonging to 22 castes were used for computation of BMI and Cormic
      index. The caste groups earning their living as labourers are found to be
      shortest (157.4+/-6.5 cm), and the caste group practising priesthood are tallest
      (168.6+/-6.6 cm). The prevalence of chronic energy deficiency is found to be
      highest (72%) among castes earning their living as daily wage labourers. The
      ANOVA on Cormic index and BMI suggests that people within the same occupational
      group are more homogeneous than those from different occupational groups. The t
      test also supports the homogeneity of the same occupational group.

PMID- 18088451
TI  - Change in hearing during 'wait and scan' management of patients with vestibular
      schwannoma.
AB  - AIM: To evaluate hearing changes during 'wait and scan' management of patients
      with vestibular schwannoma. SUBJECTS: Over a 10-year period, 636 patients have
      prospectively been allocated to 'wait and scan' management, with annual magnetic
      resonance scanning and audiological examination. RESULTS: At the time of
      diagnosis, 334 patients (53 per cent) had good hearing and speech discrimination
      of better than 70 per cent; at the end of the 10-year observation period, this
      latter percentage was 31 per cent. In 17 per cent of the patients, speech
      discrimination at diagnosis was 100 per cent; of these, 88 per cent still had
      good hearing at the end of the observation period. However, in patients with even
      a small initial speech discrimination loss, only 55 per cent maintained good
      hearing at the end of the observation period. CONCLUSION: After comparing the
      hearing results of hearing preservation surgery and of radiation therapy with
      those of 'wait and scan' management, it appears that, in vestibular schwannoma
      patients with a small tumour and normal speech discrimination, the main
      indication for active treatment should be established tumour growth.

PMID- 18088452
TI  - [Leukemia stem cells and their microenvironment--editorial].
AB  - As pioneer of tumor stem cell research, leukemia stem cell research has not only
      important theoretical significance, but also clinical application potential. The
      survival and development of stem cells are directly impacted by their
      microenvironment. The research on leukemia stem cells and their microenvironment
      are now becoming a hot topic. The author presumes that stem cells are a
      population with heterogenecity and hierarchy; any single cell from the population
      is difficult to form a clone; the interaction between the leukemia stem cell and
      its microenvironment can be described by the concept of leukemia stem cell niche.
      In this article, the leukemia cell population with heterogenecity and hierarchy
      as well as leukemia stem cell niche were summarized and discussed.

PMID- 18088453
TI  - [Remark on donor cell-derived leukemia after umbilical blood cord transplantation
      -editorial].
AB  - The recently published papers about donor cell-derived leukemia after umbilical
      cord blood transplantation and related data were reviewed, while the mechanism of
      leukemia and related problems of umbilical blood conservation were discussed. In
      view of the possibility of prenatal origin of leukemia, it is necessary to more
      systematically check the leukemia relapse cases after umbilical cord blood
      transplantation for exactly identifying the frequency of donor cell derived
      leukemia and to determine whether the transfer of pre-leukemic clones is indeed
      present.

PMID- 18088454
TI  - [Expression of PRAME gene in acute leukemia and its clinical significance].
AB  - This study was aimed to detect the expression levels of preferentially expressed
      antigen of melanoma (PRAME) gene in acute leukemia (AL) and to evaluate the
      clinical significance of PRAME gene. The quantitative detection method was
      established by SYBR Green I real-time quantitative RT-PCR, then PRAME mRNA was
      measured by this method in 55 cases of acute leukemia, out of which 43 cases were
      acute myeloid leukemia (AML), 9 cases were acute lymphocytic leukemia (ALL) and
      other types leukemia were 3 cases. In addition, expression of PRAME gene was also
      analyzed in 7 cases of non-malignant hematological diseases and 8 healthy
      volunteers. K562 cell line was used as a positive control. The results showed
      that the expression of PRAME gene was found in 35 cases of acute leukemia, the
      positive percentage was 64%. No expression could be detected in any of the non
      malignant hematological diseases and healthy volunteers. In 35 PRAME positive
      cases, 28 cases were AML, which mainly belonged to M3, M4 and M2 subtypes, and 5
      cases was ALL. In 31 fusion gene positive cases, 23 cases were PRAME positive,
      and in 24 fusion gene negative cases 12 cases were PRAME positive. No significant
      relationship was found between PRAME expression level and clinical
      characteristics (age, sex, WBC count, blast cells in BM). The expression of PRAME
      gene decreased or disappeared in 6 patients achieving complete remission (CR). It
      is concluded that the PRAME gene expresses in 64% AML patients, which mainly
      belonged to M3, M4 and M2 subtypes, no expression could be detected in any of the
      non-malignant hematological diseases and healthy volunteers. There is remarkable
      difference in the level of PRAME transcript of the 35 cases and the expression of
      PRAME gene decreases or disappears when the patients achieved complete remission.
      These results suggest that PRAME expression in acute leukemia may be a useful
      marker to detect the minimal resi-dual disease (MRD) and to determine the
      response to therapy in AL patients.

PMID- 18088455
TI  - [Expression and effect of neuropilin-1 in acute myeloid leukemic cells].
AB  - This study was aimed to investigate the expression of neuropilin-1 (NRP-1) and
      NRP-2 mRNA in myeloid leukemia cells and the effect of NRP-1 on cell
      proliferation and migration. The expressions of NRP-1 and NRP-2 mRNA in bone
      marrow mononuclear cells of 24 patients with acute myeloid leukemia and in 7
      myeloid leukemic cell lines (HL-60, KGIa, NB4, U937, HEL MEG01 and K562) were
      detected by RT-PCR. The effects of NRP-1 interfered with siRNA on proliferation
      and migration in leukemic cell line HEL were examined by MTT and migration test.
      The results showed that the expression of NRP-1 mRNA was found in bone marrow
      mononuclear cells (BMMNCS) of 24 AML patients, the positive rate was 100% and
      significantly higher than that in control group (positive rate 67%). The
      expressions of NRP-2 mRNA were seen in 79% AML patients and in 67% health
      control, there was no significant difference between them. The increased NRP-1
      expression was directly correlated with the blast percentage in both peripheral
      blood and bone marrow of AML patients (r=05, r=0.4, p<0.05). The expressions of
      NRP-1 and NRP-2 mRNA were observed in 6/7 and 3/7 myeloid leukemic cell lines
      respectively. After HEL cells were transfected with siRNA for 24 hours, the
      expression levels of NRP-1 mRNA and protein decreased obviously. Under VEGF
      action, the cell number in control group significantly increased, while the cell
      proliferation in interfered group had been not changed. After being transfected
      for 24 hours, the migration in interfered group decreased significantly. It is
      concluded that the higher level of NRP-1 mRNA is expressed in bone marrow
      mononuclear cells of leukemia patients and plays a pivotal role in proliferation
      and migration of myeloid leukemic cells. Inhibition of NRP-1 functions may
      provide a new therapeutic strategy for AML.

PMID- 18088456
TI  - [Methylation of Id4 gene promoter in acute leukemia].
AB  - This study was purpose to investigate the difference of Id4 gene promoter
      methylation between healthy individuals and acute leukemia patients. MS-PCR
      methods were used to detect the status of Id4 gene methylation in healthy
      individuals and acute leukemia patients. The results showed that Id4 gene was
      unmethylated in bone marrow samples from healthy individuals. In new diagnosed
      AML and ALL patients, the rate of Id4 gene methylation was 84% and 86%
      respectively. Id4 gene methylation was found in all 8 cases of relapsed acute
      leukemias. In 14 ALL-CR patients with Id4 gene methylation, 8 patients relapsed
      within 12 months, while in 9 ALL-CR patients with Id4 gene unmethylation only 1
      patient relapsed within 12 months. In AML-CR patients, the 12-months relapse rate
      in patients with Id4 gene methylation was 62.5%, while it was 10% in Id4 gene
      unmethylation patients, there was significant difference between them. The rate
      of Id4 gene methylation in ALL-CR patients was 64.3%, while it was 28.6% in AML
      CR patients, there was significant difference between them. In the all 39 new
      diagnosed AL patients, Id4 gene methylation could be detected in 33 patients. In
      all 8 relapsed AL patients Id4 gene methylation was found, out of 58 AL-CR cases,
      24 patients was found with Id4 gene methylation. It is concluded that as compared
      with healthy individuals, Id4 gene in acute leukemia patients was methylated in
      different degrees. The percentage of Id4 gene methylation in AL-CR group is lower
      than that in AL-non remission group. The change of Id4 gene methylation is
      thought to be associated with occurrence of acute leukemia.

PMID- 18088457
TI  - [Intracellular cytokine expression characteristics of activated T lymphocytes in
      patients with acute myeloid leukemia].
AB  - T lymphocytes are an integral part of the effective immune response against
      various tumors, but they are frequently functionally unresponsive in tumor
      bearing patients. This study was aimed to investigate the T lymphocyte function
      of patients with acute myeloid leukemia (AML) in different status through
      analyzing intracellular cytokine characteristics of T lymphocytes in AML
      patients. The T lymphocytes from 18 de nuevo AML patients in different status and
      10 healthy controls were stimulated with phorbol 12-myristate 13-acetate (PMA)
      and ionomycin in the presence of monensin, and were stained with fluorescent
      McAbs CD4-PITC, CD8-FITC and IFNgamma-PE, ILA-PE, then their T lymphocytes were
      analyzed by flow cytometry. The results showed that IFN-gamma level in CD4+ and
      CD8+ T cells of de novo AML patients was significantly lower as compared with
      healthy controls (p<0.05), while IL-4 level in CD4+ and CD8+ T cells was low too,
      there was no significant difference between de novo AML patients and healthy
      controls. In AML patients in clinical remission, IFNgamma level in CD8+ T cells
      was significantly higher than that in de novo AML patients (p<0.05), but there
      was no significant difference as compared with healthy controls (p>0.05). In
      relapsed AML patients, IFNgamma level in CD4+ and CD8+ T cells was significantly
      lower than that in healthy controls and in AML patients with CR (p<0.05), while
      IL-4 level was significantly higher than that in healthy controls and de nuevo
      AML patients (p<0.05). It is concluded that the cytokine secretion in T cell
      subsets of AML patients in different status is changed. Correspondingly, the
      Th1/Tc1 level is low after stimulating CD4+ and CD8+ T cells in peripheral blood
      of de novo AML patients, but not different from healthy controls. Though the Th1
      level in T cells of AML patients in complete remission is low, but Tc1 response
      is even enhanced as high as the healthy controls. The Th2/Tc2-like response of
      CD4+ and CD8+ T cells in relapsed AML patients obviously increases when compared
      with Th1/Tc1-like response.

PMID- 18088458
TI  - [Effects of ouabain at low concentrations on growth of leukemia cells].
AB  - This study was aimed to investigate the effects of ouabain at low concentrations
      on growth regulation in various leukemia cell lines and to determine the
      therapeutic potential of ouabain in leukemia. By using MTT, flow cytometry (FCM),
      the changes in cell growth and cell cycle of leukemia cell lines were observed
      after treating with ouabain at low concentrations (<or=10 nmol/L). The expression
      of sodium pump alpha1 subunit was evaluated by Western blot. The results showed
      that in megakaryocytic leukemia M07e and Meg-01 cell lines, the low
      concentrations of ouabain (<or=10 nmol/L) inhibited the cell growth, blocked the
      cell cycle at G1 phase, and decreased the protein expression of sodium pump
      alpha1 subunit. The same concentrations of ouabain induced the proliferation of
      lymphocytic leukemia B95 and Jhhan cell lines, increased the percentage of cells
      at S phase and G2/M phase and up-regulated the expression of sodium pump alpha1
      subunit. The basic expression of the sodium pump alpha1 subunit in M07e and Meg
      01 was lower than that in B95 and Jhhan. It is concluded that the low
      concentrations of ouabain inhibit the cell growth of the megakaryocytic leukemia
      cell lines M07e and Meg-0, which may be related with the low expression of sodium
      pump alpha1 subunit of that cell lines and the negative regulation of the protein
      induced by ouabain.

PMID- 18088459
TI  - [Expression of HSP70 mRNA and MDR1 mRNA in K562 cells induced by heat shock and
      ADM].
AB  - This study was purpose to investigate the expression levels of HSP70 and MDR1
      genes under heat shock and/or adriamycin (ADM) chemotherapy stimulation. The K562
      cells were bathed in water at 43 degrees C for 1 hour, then the heat-treated K562
      cells were collected and were cultured at 37 degrees C. The expression of HSP70
      was assayed by immunocytochemistry, the growth suppression rate of K562 cells was
      detected by MTT assay, the function of P-gp and the expressions of HSP70 mRNA,
      MDR1 mRNA were detected by flow cytometry and real-time quantitative PCR (RT-PCR)
      respectively. The results showed that (1) the synthesis of HSP70 protein in K562
      cells treated with high shock (43 degrees C) reached to high level after culture
      at 37 degrees C for 2 hours, and moved from cytoplasm to nucleolus, the
      expression of HSP70 began to decrease following 3 hours of culture at 37 degrees
      C, and gradually reached to normal level after culture at 37 degrees C for 5
      hours, the location of HSP70 expression returned to cytoplasm; (2) the
      expressions of HSP70 mRNA and MDR1 mRNA increased following 43 degrees C heat
      shock, and were 4 and 5.8 times higher than that of control group at 37 degrees C
      culture for 2 hours respectively; (3) the expression of P-gp was higher in ADM
      group than that in control. The expressions of HSP mRNA and MDR1 mRNA increased
      significantly in heat shock plus ADM group and ADM group as compared with control
      (p<0.01). It is concluded that the heat shock and ADM chemotherapy both induce
      over expression of HSP70 and MDR1 which can maintain stability of K562 cells and
      may be related to formation of the MDR in leukemia.

PMID- 18088460
TI  - [Inhibitory effect of combined transfection of p53 and AS genes on K562 cell
      proliferation].
AB  - This study was aimed to investigate the inhibitory effect of combined
      transfection of p53 and angiostatin (AS) genes on K562 cells and to explore its
      mechanism. pVTRIO2-hp53-hAS was transfected into K562 cells with lipofectamine
      2000, RT-PCR was used to determine the expression of gene of interest in
      transfected cells, MTT growth curve and flow cytometry were used to analyze the
      cell cycle for observation biological changes of cells, the cellular
      immunochemistry assay was used to observe the expression differences between
      VEGF, Bcl-2 and Bax proteins. The results indicated that the genes of interest
      have been transfected and stably expressed, the increase of K562 with genes of
      interest was slower than that without genes of interest (p<0.05). And the
      increase of K562 in double gene group was slower than that in p53 and AS groups
      (0.264+/-0.011 at last day A290 nm; 0.652+/-0.039 at last day A290 nm; 0.604+/
      0.017 at last day A290 nm respectively) (p<0.05). After transfection, the
      expressions of VEGF and Bcl-2 protein decreased, but the expressions of Bax
      increased. It is concluded that the combined transfection of p53 and AS genes
      into K562 cells shows more notable and powerful inhibition on proliferation than
      those transfected with single one gene. The synergistic mechanism of p53 and AS
      genes may be commonly influenced the pathway of Bcl-2 and Bax expression.

PMID- 18088461
TI  - [Expression of PRAME gene in adult acute leukemia and its significance in
      prognosis].
AB  - The study was aimed to investigate the expression of preferentially expressed
      antigen of melanoma (PRAME) gene in adult acute leukemia and its clinical
      significance. The expression of the PRAME gene of bone marrow was measured by
      reverse transcriptase polymerase chain reaction (RT-PCR) in 73 adult newly
      diagnosed acute leukemia patients, 3 relapsed patients, 7 patients with
      idiopathic thrombocytopenic purpura (ITP) and 8 healthy donors, as well as two AL
      cell-lines (K562 and U937). The results indicated that PRAME mRNA was expressed
      in 42.9% AML patients (n=24) and 20% ALL patients (n=4), also in two leukemia
      cell-lines K562 and U937, but not in eight health donors and seven ITP patients.
      PRAME expression not correlated to the white blood count, hemoglobin level,
      platelet count and the percentage of blasts at diagnosis, yet independent of age,
      sex, and FAB type. PRAME mRNA expression in complete remission group seems much
      higher than those in partial complete remission group and death group. The
      increased levels of expression could be found prior to the relapse in one patient
      being regularly monitored. PRAME gene was overexpressed in adult acute leukemia
      patients and leukemia cell-lines. It is concluded that the expression of PRAME is
      an indicator of favorable prognosis and can be a useful tool for monitoring
      minimal residual disease (MRD) in adult acute leukemia. Differential expression
      between adult acute leukemia patients and healthy volunteers suggests that the
      immunogenic antigens PRAME are potential candidates for immunotherapy in adult
      acute leukemia.

PMID- 18088462
TI  - [STI571 induces apoptosis of K562 cells through down-regulation of anti-apoptotic
      protein Mcl-1 and Bcl-xl expression].
AB  - This study was aimed to investigate the effect of STI571, an inhibitor of
      tyrosine kinase, on the proliferation and apoptosis of chronic myelogenous
      leukemia (CML) cells as well as expression of anti-apoptotic protein Mcl-1, and
      to explore the possible role of Mcl-1 in apoptosis-inducing mechanism. K562 cell
      line was used to observe the effect of STI571 on CML cells. Proliferation and
      cytotoxicity were analyzed by MTT assay. The apoptotic cells were labelled with
      Annexin V-FITC and PI and then analyzed by flow cytometry. The expression of
      apoptotic-related proteins in K562 cells was determined by Western blot with
      specific antibodies. The results showed that STI571 significantly inhibited the
      proliferation and induced apoptosis of K562 cells in a dose-and time-dependent
      manner. Coincidently, the protein phosphorylation on tyrosine residues was
      reduced and the expressions of anti-apoptotic protein Mcl-1 and Bcl-xl were down
      regulated after exposure to STI571. It is concluded that STI571 induces the
      apoptosis of CML cells by down-regulating the expressions of Mcl-1 and Bcl-xl,
      which suggests that Mcl-1 and Bcl-xl may play an important role in anti-apoptotic
      process of CML cells.

PMID- 18088463
TI  - [Effect of fas mRNA expression on cytochrome C-induced apoptosis of HL-60 cells
      in vitro].
AB  - The aim of this study was to investigate the effect of cytochrome C on apoptosis
      of HL-60 cells and to explore the mechanism of HL-60 cell apoptosis induced by
      cytochrome C. The HL-60 cells were treated with different concentrations of
      cytochrome C for 24 hours. The concentrations of cytochrome C were as follows: 0
      (control group), 9.375 mg/L, 18.75 mg/L, 37.5 mg/L, 75 mg/L and 150 mg/L. The
      apoptosis was analyzed by flow cytometry (FCM) after HL-60 cells were treated
      with different concentrations of cytochrome C for 24 hours. The fas mRNA
      expression changes of relevant apoptotic genes were examined by reverse
      transcription-polymerase chain reaction (RT-PCR) after HL-60 cells were treated
      with different concentrations of cytochrome C for 24 hours and were analyzed half
      quantitatively. The expressions of fas involved in HL-60 treated with different
      concentrations of cytochrome C for 24 hours were detected by Western blot. The
      results indicated that the flow cytometry (FCM) (PI straining) showed obvious
      hypo-diploid peak before G(1) phase in the treated group, and its apoptotic ratio
      increased in a dose-dependent manner. The fas mRNA expression levels of the
      relevant apoptotic genes could be detected by RT-PCR after HL-60 cells treated
      with different concentrations of cytochrome C for 24 hours, and the expression of
      fas mRNA in HL-60 cells was increased by cytochrome C in dose-dependent manner
      within range of 0-37.5 mg/L. It is concluded that the cytochrome C up-regulates
      expressions of fas mRNA and their protein so as to induce apoptosis of the HL-60
      cells.

PMID- 18088464
TI  - [Effect of arsenic trioxide on the expression of apoptosis-related genes in NB4
      cells].
AB  - The aim of this study was to investigate the gene expression profiles of acute
      promyelocytic leukemia (APL) cell line NB4 treated with arsenic trioxide (As2O3)
      by using cDNA microarray. cDNA probes were prepared through reverse transcription
      from mRNA of NB4 cells treated with or without arsenic trioxide. The probes were
      labeled with Cy3 and Cy5 fluorescence dyes individually, hybridized with cDNA
      microarray representing 201 different human genes, and their fluorescent
      intensities were scanned. The genes were screened through the analysis of the
      difference in the gene expression profile. The results showed that after the
      treatment of arsenic trioxide (2 micromol/L), 6 genes were up-regulated, and 12
      genes related to apoptosis and signal transduction were down-regulated. The p21,
      survivin, cdc2 and Wee1Hu genes may be related to the differentiation and/or
      apoptosis of NB4 cells induced by As2O3. It is concluded that p21, survivin, cdc2
      and Wee1Hu may play an important role in the mechanism underling arsenic trioxide
      mediated NB4 cell apoptosis.

PMID- 18088465
TI  - [Mitochondrial membrane potential at HL-60 cell apoptosis induced by cytarabine].
AB  - This study was aimed to investigate the changes of mitochondrial membrane
      potential (DeltaPsim) of HL-60 cells induced by cytarabine and the correlation
      between mitochondrial membrane potential and apoptosis of HL-60 cells. HL-60
      cells were stained with Rhodamine 123; change of mitochondrial membrane potential
      of HL-60 cells was detected by flow cytometry. AO/EB staining and flow cytometry
      were used to examine the apoptosis of HL-60 cells. The results showed that the
      levels of HL-60 cell DeltaPsim in experimental groups decreased after cultured
      for 6 hours. In Ara-C 0.05 mg/ml group, rhodamine 123 fluorescence intensity in
      mitochondria of HL-60 cells at 6, 12, 24 hours were 117.9+/-7.6, 100.9+/-7.7,
      87.6+/-10.7, respectively, there was significant difference between the different
      culture groups (p<0.05). In Ara-C 0.1 mg/ml group, rhodamine 123 fluorescence
      intensity in mitochondria of HL-60 cells at 6, 12, 24 hours were 111.9+/-10.1,
      86.6+/-9.2, 68.4+/-12.2, respectively, there was significant difference between
      the different culture groups (p<0.05); rhodamine 123 fluorescence intensity was
      significantly different between the two groups at 12, 24 hours (p<0.05). In Ara-C
      0.05 mg/ml group, the apoptosis rate of HL-60 cells at 6, 12, 24 hours were
      (41.2+/-3.0)%, (53.7+/-5.1)%, (65.8+/-2.6)% respectively, there was significant
      difference between the different culture groups (p<0.01); In Ara-C 0.1 mg/ml
      group, the apoptosis rate of HL-60 cells at 6, 12, 24 hours were (45.7+/-4.1)%,
      (58.2+/-4.3)%, (70.1+/-2.3)% respectively, there was significant difference
      between the different culture groups (p<0.01); the apoptosis rates showed no
      significantly difference between the two groups at same time. The changes of
      mitochondrial membrane potential and apoptosis rate of HL-60 cells were
      significantly negatively correlated. In Ara-C 0.05 mg/ml group, r was -0.89,
      p<0.01, while in Ara-C 0.1 mg/ml group, r was -0.76, p<0.01. It is concluded that
      the mitochondrial membrane potential on HL-60 cells decrease at HL-60 cells
      apoptosis induced by Ara-C, therefore the reduction of mitochondrial membrane
      potential may be one of the important mechanisms at the induced apoptosis.

PMID- 18088467
TI  - [Apoptosis of multiple myeloma cells induced by 8-Cl-cAMP in vitro].
AB  - The study was aimed to investigate the possible effects of 8-chloroadenosine 3',
      5'-monophosphate (8-Cl-cAMP) on the multiple myeloma cells. The multiple myeloma
      cell line RPMI8226 was used as in vitro models. The effect on growth inhibition
      of RPMI8226 cells was evaluated by cell growth and viability curve. DNA fragment
      was visualized by agarose gel electrophoresis. The amount of apoptosis cells was
      measured by flow cytometry. Meanwhile Western blot assay were used to detect the
      change of several key cell cycle regulatory proteins CDK2 and cyclin E in these
      cells before and after the treatment. The results showed that low dose 8-Cl-cAMP
      (1-30 micromol/L) inhibited the proliferation and viability of RPMI8226 cells
      significantly. Agarose gel electrophoresis of DNA revealed the apoptosis
      characteristic "ladder" pattern. Apoptosis was also confirmed by flow cytometry.
      In addition, 8-Cl-cAMP was able to inhibit the cell growth through modulating
      expression of cell cycle regulators CDK2 and cyclin E. It is concluded that 8-cl
      cAMP inhibits the proliferation and induce apoptosis of multiple myeloma cells
      effectively.

PMID- 18088466
TI  - [Effects of As2O3, dexamethasone and thalidomide on apoptosis and cytoplasmic
      [Ca2+] of myeloma cell line U266].
AB  - To investigate the influence of As2O3, dexamethasone (Dex) and thalidomide (Thal)
      on apoptosis-induced myeloma cell line U266 cytoplasmic calcium concentrations
      ([Ca2+]i), U266 cells were incubated in the culture of RPMI 1640 with 15% FBS in
      24-well plate and exposed to different concentrations of As2O3, Dex and Thal for
      8 hours, respectively, then cell apoptosis was analyzed by fluorescence
      microscopy and flow cytometry (FCM) with Annexin V-FITC/PI double staining, and
      cytoplasmic free calcium were detected on FCM through Fluo-3/AM loading. The
      results indicated that (1) apoptotic cells were gradually increased with
      enhancement of As2O3, Dex and Thal concentrations; (2) apoptotic cell rates
      increased from 0.56% in control to 31.54%, 28.35% and 21.97% respectively after
      treatment with As2O3, Dex and Thal; (3) As2O3, Dex induced U266 cell apoptosis
      accompanied with raise of [Ca2+]i; (4) [Ca2+]i had no statistically significant
      changes in Thal-induced apoptotic U266 cells. It is concluded that the raise of
      [Ca2+]i is one of the mechanisms for As2O3 and Dex-induced U266 cells apoptosis,
      whereas Thal-induced U266 apoptosis has no significant relation to [Ca2+]i
      changes.

PMID- 18088468
TI  - [Correlation of HLA-alleles with aplastic anemia].
AB  - To investigate the correlation between the HLA genes and pathogenesis of aplastic
      anemia (AA), polymerase chain reaction with specific sequence primers (PCR-SSP)
      method was used to HLA typing in 82 patients with AA and 400 normal healthy
      individuals as control. The results showed that A*2301 (1.84%), B*5501 (4.36%)
      and DRB1*0901 (23.48%) gene frequency in AA patients were significantly higher
      than those in controls (relative risk: RR=5.0253, 3.3645, 2.1269, chi2=4.6634,
      6.3120, 9.1511 respectively) (p<0.01). In contrast, DRB1*1301 (1.23%) gene
      frequency was significantly lower in AA than that in controls, RR=0.2257,
      chi2=6.6629 (p<0.01). It is concluded that A*2301, B*5501 and DRB1*0901 genes may
      be considered as the risk markers while DRB1*1301 gene as a protective marker of
      AA.

PMID- 18088469
TI  - [Expression of HLA-DRB1*15 genotype in children with acquired aplastic anemia and
      its relation to effect of immunosuppressive therapy].
AB  - This study was purpose to investigate the frequency of HLA-DRB1*15 expression in
      children with aplastic anemia (AA) and its relation to effect of
      immunosuppressive therapy. HLA-DR genotypes were detected by SSP-PCR in 40
      patients with acquired aplastic anemia and 107 normal controls, and the
      expressions of HLA-DR gene in AA patients and normal controls were compared. 32
      out of 40 patients were treated with immunosuppressive therapy, which included
      antilymphocyte globulin combining with cyclosporine or cyclosporine alone, the
      relation of HLA-DRB1*15 expression to efficacy of immunosuppressive therapy and
      relapse of AA was explored. The results showed that the mean age of the patients
      was 9.0 years with a ratio of male to female 1.5:1. The frequency of HLA-DRB1*15
      genotype expression in patients with idiopathic aplastic anemia was 51.5%
      (17/33), which was markedly higher than that of healthy controls (20.6%, p<0.01).
      All of 7 patients with second acquired aplastic anemia showed negative expression
      of HLA-DRB1*15. The rates of all responses, including complete remission and
      partial remission (CR+PR), and CR to immunosuppressive therapy in 16 patients who
      bared HLA-DRB1*15 were 93.8% and 87.5% respectively, which were higher
      significantly than those of patients without bearing HLA-DRB1*15 (56.3% and
      31.3%, p<0.01). Relapse occurred in 5 patients who bared HLA-DRB1*15 genotype. It
      is concluded that the frequency of HLA-DRB1*15 genotype expression in children
      with AA is significantly higher than that in normal controls, and the
      immunosuppressive therapy for patients bared HLA-DRB1*15 shows favourable effect
      with high incidence of complete remission.

PMID- 18088470
TI  - [Effect of human bone marrow mesenchymal stem cells on T lymphocyte killing K562
      cells].
AB  - The objective of this study was to investigate the effect of human bone marrow
      mesenchymal stem cells (MSCs) on T lymphocyte killing K562 cells. MSCs were
      isolated from bone marrow and cultured, T cells were harvested by using nylon
      column method from peripheral blood. The T cells were co-cultured with MSCs, the
      phenotype expressions of T cell subsets were detected by flow cytometry. Killing
      effects of T cells (culture alone and co-culture with MSCs) on K562 cells were
      detected by LDH, expressions of IFN-gamma and IL-4 were detected by ELISA. The
      results showed that after T cells were co-cultured with MSCs for three days, the
      proportion of CD4+ and CD4+CD25+ T cells raised significantly (p<0.05) as
      compared with group of culture alone, but the proportion of CD8+ T cell were not
      significantly changed (p>0.05). In group of T cells co-cultured with MSCs,
      killing effects of T cells on K562 cells weakened, at the same time, expression
      of IFN-gamma decreased while expression of IL-4 increased. It is concluded that
      the MSCs weaken killing effects of T cells on K562 cells, which associates with
      increase of CD4+CD25+ T cell subsets and changes of IFN-gamma and IL-4 levels.

PMID- 18088471
TI  - [Human cord blood adult stem cells differentiate into hepatocyte-like cells in
      vitro].
AB  - The aim of this study was to investigate the feasibility of the human cord blood
      adult stem cells (ASCs) to differentiate into hepatocytes in vitro induced by
      combined stimulation with hepatocyte growth factor (HGF), stem cell factor (SCF)
      and leukemia inhibitory factor (LIF). The adult stem cells were obtained through
      density gradient centrifugation and magnetic activated cell sorting (MACS). The
      adult stem cells were cultured in DMEM with HGF (10 ng/ml)+SCF (10 ng/ml)+LIF (10
      ng/ml) in induced group I. In induced group II the enriched cells were cultured
      in DMEM with SCF (10 ng/ml)+LIF (10 ng/ml) and the undifferentiated cells acted
      as the control group without the factors. The morphology of cells was observed by
      the inverted phase contrast microscopy; the expression of albumin (Alb), human
      hepatocyte cytokeratin (CK18) and alpha-fetoprotein (AFP) were detected by
      immunofluorescence, immunohistochemistry and RT-PCR assay in the 21-day culture.
      Alb secreted by hepatocytes in the medium was determined by radioimmunoassay
      (RIA) at day 7, 14, 21, 23 and 25. The results showed that the shapes of ASCs
      changed and their sizes and number increased in the course of culture in group I.
      After being induced for three weeks, the cells turned round and resembled
      hepatocyte-like cells. The mRNA for Alb could be detected by RT-PCR in the
      differentiated adult stem cells in group I, and the mRNA for AFP was poorly
      detected by RT-PCR at day 21. Alb and CK18 were positive through
      immunofluorescence and immunohistochemistry at day 21, compared with group II and
      the control group. In group I, Alb in the medium significantly increased,
      compared with control group, and reached the highest level at day 21, then
      decreased at day 23. It is concluded that under some definite inducing
      conditions, human cord blood adult stem cells can differentiate into hepatocyte
      like cells and HGF plays a critical role during the course.

PMID- 18088472
TI  - [Effects of mesenchymal stem cells on cell cycle and apoptosis of hematopoietic
      tissue cells in irradiated mice].
AB  - The aim of this study was to investigate the effect of mesenchymal stem cells
      (MSCs) on cell cycle and apoptosis of thymus, spleen and bone marrow cells in
      mice totally irradiated with sublethal dose, and to explore its mechanisms.
      BALB/c mice irradiated with 5.5 Gy 60Co gamma-ray were randomly divided into
      control group and MSC group. Mice in MSC group were infused with 0.4 ml
      containing 2.5x10(7)/kg of MSCs through tail vein at 1 hour after irradiation.
      Mice in control group were infused with 0.4 ml normal saline. The cell apoptosis
      and cell cycle of thymus, spleen and bone marrow cells were detected by flow
      cytometry at 6, 12, 24 and 72 hours after irradiation and the P53 protein
      expressions in thymus and bone marrow cells were assayed by immunohistochemistry
      at 12 hours after irradiation. The results showed that the arrest of cells in
      G0/G1 and G2/M phase, and decrease of cells in S phase appeared at 6 hours after
      irradiation, those reached peak respectively at 12 hours in thymus cells, 6 hours
      in spleen and 24 hours in bone marrow, then the cell counts in G0/G1 phase
      decreased and the cell counts in S and G2/M phases increased. At 72 hours the
      cell counts in G0/G1 phase were less than the normal level and the cell counts in
      S phase were more than the normal level. The above changes of cell cycle in
      thymus and spleen were more rapid in spleen and more obvious in amplitude than
      that in bone marrow, the change of cell cycle in MSC group was more rapid and
      obvious than those in control group. After irradiation the apoptosis cells
      increased from 6 hours, reached the highest level at 12 hours and decreased to
      the normal level gradually after 24 hours in two groups; the apoptosis rates in
      spleen and thymus cells were higher than that in bone marrow cells. In comparison
      with the control group, the apoptosis rate in thymus cells at 12 hours, in spleen
      cells at 12 and 24 hours, and in bone marrow cells at 24 hours were fewer in MSC
      group. The cells expressing P53 protein in control group were more than that in
      MSC group. It is concluded that the MSCs accelerate the running of cell cycle in
      these hematopoietic tissue cells of irradiated mice, reduce the cell apoptosis
      and promote the recovery from injuries in hematopietic and immunological organs,
      thus protect the irradiated mice at early stage.

PMID- 18088473
TI  - [Long-term subculture and biological characterization of the murine bone marrow
      endothelial cell line].
AB  - The murine bone marrow endothelial cell line (mBMEC) has been maintained by means
      of subculture and cryopreservation for over 10 years since it was established in
      our laboratory. This study was aimed to newly identify biological characteristics
      of this cell line for further study. The cultured mBMEC cells were observed by
      inverted microscopy and transmission electron microscopy (TEM). PECAM-1 (CD31)
      and von Willebrand factor (vWF) were detected by immunofluorescent staining. The
      phagocytotic activity of the cells in culture was tested by using fluorescent
      acetylated low-density lipoprotein (Dil-Ac-LDL). The cell growth kinetics
      analysis and karyotype analysis were performed. The results showed that the
      adherent cells were mostly elliptical, rounded and spindle-shaped, and some of
      them connected to each other to form cord- and network-like arrangements in mBMEC
      cultures at subconfluence. The adherent cells grew up to confluence as a
      cobblestone-like monolayer. Several ultrastructural features of the endothelial
      cells could be observed in TEM sections of the cultured cells. More than 94% of
      mBMEC cells were positive for either CD31 or vWF. The phagocytotic ingestion of
      Dil-Ac-LDL occurred in 98.5% of cells. In normal culture conditions, the cells
      grew with a mean population doubling time of 54.6 hours and the maximal mitotic
      index was 38 per thousand in the rapid growth period. The colony yields were
      4.33% to 7.40% depending on the plating density of cells. Karyotypes of all the
      cells were aneuploidy with a greater percentage of hyperdiploid. It is concluded
      that mBMEC cells retain the fundamental properties of endothelial cells, but the
      growth kinetics and biological behaviors are slightly different from those in the
      early days after the establishment of this cell line.

PMID- 18088474
TI  - [Monitoring IgH levels in patients with B-cell malignancy by real-time
      quantitative PCR after hematopoietic stem cell transplantation and its
      significance].
AB  - The study was purpose to evaluate the value of real time quantitative-PCR for
      monitoring IgH level in patients with B-cell malignancy after hematopoietic stem
      cell transplantation (HSCT). Quantification of IgH levels was performed on bone
      marrow mononuclear cells from 9 patients with B-cell malignancy before and after
      HSCT by PCR using the consensus JH TaqMan probe in combination with an allele
      specific oligonucleotide (ASO) upstream primer. The IgH levels was normalized by
      control gene GAPDH. The results indicated that the reproducible sensitivity of RQ
      PCR was 1 copy, the significant reduction of IgH copies was observed in bone
      marrow samples of 9 patients at one month post HSCT (6.67x10(3)/10(6) GAPDH vs
      29/10(6) GAPDH, p<0.01). 3 out of 9 patients who achieved complete clinical and
      molecular cytogenetic remission (CCyR) contained persistently measurable low IgH
      level of 10(2)/10(6) GAPDH within 15 months and no detectable IgH at 18 months
      post HSCT. Whereas 5 out of 9 patients whose IgH copies were less than
      10(2)/10(6) GAPDH within 3 months and less than 10(3)/10(6) GAPDH 3 months post
      HSCT achieved a sustained complete remission (CR). IgH copies in one patient were
      4.5x10(3)/10(6) GAPDH at 3 months post HSCT, who relapsed at 4 months post HSCT.
      The median levels of tumor contamination in the stem cell harvests from 8
      patients measured by RQ PCR were 3.68x10(2) (0-1720)/10(6) GAPDH. RQ PCR showed
      that PBPC harvests were less contaminated than BM harvests [75 (0-890)/10(6)
      GAPDH vs 1.1x10(3) (527-1720)/10(6) GAPDH, p<0.05]. 8 patients whose stem cell
      harvest were avaiable for RQ PCR were still in CR despite of the tumor
      contamination. The level of tumor contamination in stem cell harvest well
      correlated with IgH levels at diagnosis and one month after HSCT (r=0.810,
      r=0.708, p<0.05). It is concluded that RQ PCR can effectively monitor the IgH
      levels in patients with B-cell malignancy after auto-HSCT. 10(3)/10(6) GAPDH
      within 3 months post HSCT may be a cut-off level of IgH copies, which may be used
      to evaluate different prognoses of patients.

PMID- 18088475
TI  - [Ex vivo chemical modification of graft cells by methoxy polyethylene glycol
      alleviates graft versus host disease after haploidentical stem cell
      transplantation in mice].
AB  - This study was aimed to explore the effect of ex vivo chemical modification of
      graft cells with methoxy polyethylene glycol (mPEG) on graft versus host disease
      (GVHD) after haploidentical stem cell transplantation in neonatal mice and its
      influence on activity of the stem cells. The modified and non-modified spleen
      cells of adult CB6F1 mice were injected into the abdominal cavity of neonatal
      BALB/c mice with 5x10(6) spleen cells per mouse, and GVHD were measured by spleen
      index (SI). Furthermore, the modified and non-modified mixture of bone marrow and
      spleen cells (BMS) were transplanted to haploidentical lethally irradiated adult
      BALB/c mice via tail vein with 2x10(5) BMS per mouse, and the colony forming
      units of spleens (CFU-S) were counted on the eighth day after irradiation. The
      results indicated that SI1 in modification group were lower than that in non
      modification group, and SI2 in modification group was <1.3, showing that GVHD in
      modification group were less severe. The numbers of CFU-S formed in both
      modification group and non-modification group were not significantly different
      (p>0.05), indicating that the activity of the stem cells were not affected by
      mPEG modification. In conclusion, the modification of graft cells with mPEG
      alleviates GVHD after haploidentical stem cell transplantation in neonatal mice,
      and do not influence the activity of the stem cells.

PMID- 18088476
TI  - [Engraftment of ex vivo expanded mononuclear cells from human umbilical cord
      blood in NOD/SCID mice].
AB  - This study was purpose to explore the effect of combination of SCF, FL, TPO
      without serum and stroma on the ex vivo expansion of the mononuclear cells
      derived from umbilical cord blood (CB) and to evaluate the proper infused time
      and implantation of expanded cells. Mononuclear cells derived from CB were
      cultured with the combination of SCF, FL and TPO for 14 days. At 0, 7, 10 and 14
      days, the total mononuclear cells in culture were counted, CD34+ cells and
      CD34+CXCR4+, CD34+CD49d+ cells were assayed by flow cytometry, and CFU were
      determined. Mononuclear cells from CB cultured for 7 days ex vivo in serum- and
      stroma-free medium containing FL+SCF+TPO were infused into sublethally irradiated
      NOD/SCID mice. Six weeks after transplantation, the human cells were assessed by
      flow cytometry and PCR. The results showed that after culturing ex vivo in the
      presence of SCF+FL+TPO for 14 days, the total number of nuclear cells
      significantly increased in the early stage of culture, CD34+, CD34+CD49d+ cells
      reached a peak level at 7 days and then decreased, while the peak level of CFU,
      CD34+CXCR4+ cells was at 10 days, then decreased. Human hematopoietic cells could
      be detected in the marrow of the recipients at 6 weeks after infusion and the
      rate of success of NOD/SCID mice implanted with the expanded cells was higher
      than mice transplanted with fresh sample and control (p<0.05). It is concluded
      that day 7-10 may be an optimal harvest time for transplantation. The expanded
      cells with FL+SCF+TPO can be engrafted into the bone marrow of sublethally
      irradiated NOD/SCID mice. The engrafting potential of cord blood may be enhanced
      via up-regulating CXCR4 and CD49d expression on the CD34+ cells.

PMID- 18088477
TI  - [Human/mouse chimeric anti-CD20 monoclonal antibody enhances antigen presentation
      in dendritic cells and induces anti-lymphoma CTL effects].
AB  - In order to investigate the cellular immunoresponses mediated by chimeric anti
      CD20 monoclonal antibody (anti-CD20 McAb) through dendritic cells (DCs),
      mononuclear cells were isolated from human peripheral blood (PBMNC) and DCs from
      PBMNCs in vitro were generated with normal methods. Human CD20 positive lymphoma
      cell line-Raji cells were treated with different methods including treatment with
      anti-CD20 McAb (group R), treatment with heat-induced apoptosis (group A) and
      treatment with anti-CD20 McAb+heat-induced apoptosis (group R+A), then Raji cells
      treated with above-mentioned methods as tumor antigen were loaded on DCs. The
      phagocytosis of DCs to tumor antigen was observed by transmission electron
      microscope (TEM), the auto-mixed lymphocyte reaction was performed with antigen
      primed DCs, the release of INF-gammafrom effector cells was detected by ELISPOT,
      the killing of effector cells on Raji cells was assayed by MTT. The results
      showed that under TEM, no pronounced phagocytosis of DCs was seen in group R,
      while the phagocytosis of apoptotic bodies could be easily seen in group A and
      the more cell fraqments were observed in group R+A. The FCM indicated that the
      expressions of CD80, CD86 and HLA-DR on DCs in 3 experimental groups were higher
      than those in group control (p<0.05), while expression positive rate in group R+A
      was higher than those in group R and A (p<0.05). The detection of lymphocyte
      surface antigen revealed that proportions of CD8+ cells in all experimental
      groups were higher than those in group control (p<0.05), count of CD56+ cells in
      group R and R+A increased, as compared with group A and control, difference was
      significant (p<0.05). ELISPOT assay indicated that amount of cells releasing IFN
      gamma in all experimental groups was higher than that in group control, and also
      number of spots in group R+A significantly higher than that in other groups at
      effector-targetor ratio=1:10 (p<0.05). The results of killing assay demonstrated
      that killing rate on Raji cells in all experimental groups increased as compared
      with group control (p<0.05), while killing rate in group R+A was higher than that
      in group R and A. It is concluded that anti-CD20 McAb can mediate DC to induce
      cellular immunoresponse against lymphoma, that is, to stimulate and amplify
      specific CTLs and NK cells. Anti-CD20 McAb combined with DCs primed by heat
      stressed tumor cells as antigen can further enhance cellular immunoresponse
      against lymphoma.

PMID- 18088479
TI  - [Effect of Mycobacterium phlei F.U.36 suspended liquor on culture and
      proliferation of dendritic cells derived from human umbilical cord blood in
      vitro].
AB  - To investigate the effect of mycobacterium phlei F.U.36 suspended liquor
      (Utilin"s", U) on the culture and proliferation of dendritic cells (DCs) derived
      from human umbilical cord blood in vitro, the mononuclear cells (MNCs) were
      isolated from human umbilical cord blood and cultured with RPMI 1640 in the
      control group. Test groups consisted of Utilin"s" group (only Utilin"s"), GTI
      group (GM-CSF, TNF-alpha, IL-4) and GTIU group (GM-CSF, TNF-alpha, IL-4 and
      Utilin"s"). MNCs in all test groups were cultured with RPMI-1640. The growth of
      DCs was observed by the light microscopy, the phenotypes of DCs were determined
      by flow cytometry on the 10th day of culture, and some harvest cells were stained
      with Wright-Giemsa, then observed and photographed under the oil immersion
      objective. The results showed that the test groups all displayed some number of
      typical DCs; both CD1a positive cell rate and HLA-DR positive cell rate of the
      Utilin"s" group were higher than those of the control; HLA-DR positive cell rate
      of GTIU group increased most significantly and much higher than that of the GTI
      group. It is concluded that mycobacterium phlei F.U.36 not only promotes the
      proliferation of DCs derived from human umbilical cord blood in vitro, but also
      co-operates with rhGM-CSF, rhTNF-alpha and rhIL-4 in promoting the maturity of
      DCs.

PMID- 18088478
TI  - [Molecular mechanisms of low intensity pulsed ultrasound-mediated cellular
      behavior in human primary macrophages].
AB  - The aim of this study was to explore the molecular mechanisms of the effect of
      low intensity pulsed ultrasound (LIPUS) on human primary macrophage functions.
      Macrophage phagocytosis was analyzed using fluorescein isothiocyanate (FITC)
      labelled Escherichia coli (E.Coli); focal complex and extracellular matrix
      metalloproteinase inducer (EMMPRIN) were observed by fluorescence microscopy; the
      secretion of metalloproteinases (MMPs) was examined by gelatin zymography, and
      the expressions of EMMPRIN and extracellular signal-regulated kinases (ERKs) were
      detected by Western blot. The results indicated that LIPUS accelerated
      macrophages to phagocytose E.Coli (29.81+/-0.36 vs 18.00+/-0.78), promoted the
      protein expressions of EMMPRIN and MMPs, increased the level of protein tyrosine
      phosphorylation, and induced the phosphorylation of ERKs. Furthermore, the above
      functions were only found in adherent macrophages, and were inhibited or
      decreased by mitogen activated protein kinase kinase (MAPK kinase, MEK) inhibitor
      PD98059 and RGD (Arg-Gly-Asp peptide), one of main integrin recognition
      sequences. It is concluded that the effect of LIPUS on macrophages depends on
      cell adhesion, and relates to integrin-MEK-ERK pathway.

PMID- 18088481
TI  - [Enhancing transfection efficiency of polyethylenimine by a hydrophobic peptide
      from bee venom].
AB  - The study was aimed to investigate the possibility of enhancing transfection
      efficiency of branched polyethylenimine (BPEI) in HeLa cells by hydrophobic tail
      of bee venom peptide (melittin). Hydrophobic tail of melittin was synthesized and
      its membrane permeable activity was evaluated by hemolysis test. The peptide was
      mixed with BPEI and the transfection efficiency was determined in HeLa cells by
      using green fluorescent protein gene (GFP) as a reporter gene. The cytotoxicity
      of the mixture was analyzed by MTT assay at 24 hours after transfection. The
      results indicated that the synthesized peptide had permeable activity leading to
      hemolysis in both neutral and acidic solution. At optimal condition, the peptide
      could significantly improve the transfection efficiency of BPEI and the
      cytotoxicity of the mixture was lower than BPEI itself. It is concluded that
      hydrophobic tail of melittin may be a potential enhancer to improve transfection
      efficiency mediated by cationic polymers in difficult to transfect cells.

PMID- 18088480
TI  - [Construction and selection of RNAi plasmid vector for suppressing GATA-3 gene
      expression].
AB  - GATA-3 plays a central role in the Th2-mediated immunoreaction. This study was
      aimed to construct and select plasmid vectors of siRNA which can effectively and
      specifically suppress the gene expression of GATA-3. Plasmid including PSi338,
      PSi717 and PSi1232 were designed and constructed for GATA-3 regarded as target
      gene and transfected into murine P815 cells. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) and Western blot were used to detect the inhibition of
      GATA-3 mRNA as well as its protein in P815 cells. The results demonstrated that
      the expressions of mRNA and protein of GATA-3 in P815 cells were inhibited
      significantly by both of PSi338 and PSi717. It is concluded that PSi338 and
      PSi717 siRNA plasmid vectors have been successfully constructed, and both vectors
      are effective and specific siRNA plasmids for suppressing GATA-3 gene expression.

PMID- 18088482
TI  - [Correlation of polymorphism in IL-6 gene promoter with BMI, inflammatory
      factors, and pathogenesis and progression of CHD].
AB  - This study was aimed to explore the correlation between IL-6 gene promoter
      polymorphisms and coronary heart disease (CHD) by investigating the polymorphisms
      (-572G/C, -597G/A) in IL-6 gene promoter area, body mass index (BMI),
      inflammatory factors and other biochemical parameters in Han nationality of North
      China. The genotypes of IL-6 gene promoter-572G/C, -597G/A were detected by
      fluorescent probe hybridization with fluorescent resonance energy transfer and
      melting curve techniques in 194 CHD patients and 123 healthy people as control.
      The effects of genotype on plasma lipids, apoproteins, high sensitive C-reactive
      protein (hsCRP) and BMI were also studied. Logistic regression was performed to
      observe the risk factors of CHD. The results indicated that genotype of IL-6 gene
      promoter -597G/A polymorphism in 7 cases were GA and were GG in others, whereas
      no AA genotype had been found and no associations between polymorphism of IL-6
      gene -597G/A, BMI and inflammatory factors were found. No differences had been
      found between the frequencies of IL-6 gene -572G/C genotypes and alleles in CHD
      and control group. However, significant difference was found between the G allele
      carrier (GG+GC) and non-G allele carrier (CC) of CHD and control group
      (p=0.0425). In the control group, median levels of systolic blood pressure of G
      allele carrier were significant higher than non-G allele carrier (p=0.02). Among
      all the subjects, median levels of BMI, hsCRP and systolic blood pressure in the
      group of G allele carrier were significantly higher than that in the group of non
      G allele carrier, p values were 0.026, 0.022, 0.005 respectively. Multivariate
      logistic regression analysis showed that age, triglyceride, sex, high blood
      pressure, apoprotein C2, cholesterol and lipoprotein-a) were the risk factors for
      CHD, and apoprotein A1 was a protective factor. The G allele of IL-6 gene -572G/C
      has been not found to be a risk factor for CHD. It is concluded IL-6 gene -597G/A
      polymorphism is not correlated with the susceptibility to CHD; IL-6 gene -572G/C
      polymorphism may be correlated with the susceptibility to CHD in Han nationality
      of North China, the mechanisms may be related with the changes of BMI, hsCRP and
      blood pressure levels resulted from the polymorphism of IL-6 -572G/C.

PMID- 18088483
TI  - [Analysis of natural killer cell immunoglobulin-like receptor gene family in HLA
      identical sibling].
AB  - The aim of study was to analyze natural killer immunoglobulin (Ig)-like receptor
      (KIR) gene content in HLA-identical sibling and to investigate the possibility of
      their KIR match. Samples were genotyped for HLA by Luminex method and polymerase
      chain reaction sequence based typing, the KIR gene was detected by polymerase
      chain reaction sequence-specific primers. The results showed that 17 KIR genes
      could be observed in the 27 pairs HLA-A, -B, -Cw and -DRB1 locus identical
      sibling samples. All individuals contained KIR3DL3, KIR3DP1, KIR2DL4 and
      KIR3DL2.; 20 different KIR genotypes and 12 haplotypes have been found, the most
      common KIR genotypes was 2,2 with frequency 29.6% and KIR haplotype was 2 with
      frequency 53.0%. The A KIR haplotype was the most prevalent with frequency 67.2%;
      12 pairs (44.4%) HLA identical sibling donor-recipients showed KIR match in
      genotype and haplotype, 13 pairs (48.1%) with one KIR haplotype mismatch and 2
      pairs (7.4%) with two KIR haplotype mismatch; 1 pair was matched between donor
      KIR2DL1 and patient HLA-Cw (Lys80) ligand, 17 pairs were matched between
      KIR2DL2/KIR2DL3 and HLA-Cw (Asn80) ligand, 5 pairs were matched between KIR3DL1
      and HLA-Bw4 ligand. It is suggested that the probability of KIR mismatch is high
      in HLA-identical sibling.

PMID- 18088484
TI  - [Identification and sequence analysis of a novel HLA-B*3936 allele].
AB  - The aim of study was to confirm the novel HLA allele HLA-B*3936 in Chinese
      population and to analyze its sequence. The proband was a cord blood donor in the
      Zhejiang province. DNA was extracted from whole blood by PEL-FREEZ DNA extraction
      kit. The amplification of HLA-B exons 2 - 4 of the proband was performed by
      allele specific primer PCR and the amplified product was sequenced
      bidirectionally with primers. The sequencing results showed HLA-B alleles of the
      proband as B*4002 and the novel allele. The sequences of the novel allele have
      been submitted to GenBank (DQ242650, DQ242651, DQ242652). After Blast HLA
      analysis, the novel allele showed four nucleotide differences with HLA-B*3901 at
      nucleotide position 527 T-->A, 538 C-->T, 539 T-->G, 544 A-->G in exon 3. It
      resulted in three amino acid change from Val to Glu at codon 152, Ile to Trp at
      codon 156, Thr to Ala at codon 158. The result suggested that this allele is a
      novel allele and has been officially named HLA-B*3936 by the WHO Nomenclature
      Committee.

PMID- 18088485
TI  - [Protective effects of DMSO on function of lyophilized human platelets].
AB  - This study was aimed to investigate the effects of DMSO on platelets during pre
      treatment for lyophilization, including centrifugation, washing and loading
      trehalose. After pre-treatment for lyophilization, the expression of platelet
      membrane surface glycoprotein (GP) including CD62p and PAC-1 was analyzed by FCM
      before and after induction with thrombin, the mean platelet volume (MPV) and
      platelet maximal aggregation with several platelet inducers were investigated.
      The results showed that the expression rates of CD62p and PAC-1, as the platelet
      activation signs, increased and were 30.37% and 15.01% respectively in group
      without DMSO after pre-treatment. And their differences in comparison with
      control were statistically significant, but that of CD62p was 10.72% and PAC was
      10.11% in group with DMSO, in comparison with group without DMSO respectively,
      their differences were statistically significant after diluting with DMSO, CD62p
      was re-expressed to 54.39% in group with DMSO and more than that in group without
      DMSO and lower than control statistically significant. PAC-1 was re-expressed to
      49.28% in group with DMSO and more than that in group without DMSO (p<0.01) and
      reached to control. Platelet maximal aggregations induced by thrombin, restocetin
      and propyl gallate were 92.76%, 91.24% and 89.66 respectively in group with DMSO.
      These were closed to that in control group and in group without DMSO. But the
      aggregation induced by ADP was 34.33%, it was less than control (p<0.01) and more
      than that in group without DMSO (p<0.01). It is concluded that DMSO can inhibit
      the expression of CD62p and PAC-1 on platelet in vitro. But when diluted with
      plasma, platelets can express CD62p and PAC-1 induced by thrombin and be led to
      aggregate by several inducers, so the inhibitory effects of DMSO on platelet
      activation are reversible. DMSO play roles in inhibitor damage from platelet
      activation and cryoprotectant. This property of DMSO is very important in
      research of platelets lyophilization.

PMID- 18088486
TI  - [Quality control of indispensable reagent RBC for ABO typing].
AB  - The reagent RBC of known blood group is indispensable reagent for detecting
      antibody in serological identification of ABO blood group. To elevate the
      accuracy of detection and solve problems for standardization and quality control
      of prepared reagent RBC, the detection of specificity and affinity of reagent
      RBC, shaking test, flow cytometry and atomic force microscopy were performed. On
      the basis of screening and establishing the reagent for quality control, methods
      for quality inspection and quality control were established. The results
      indicated that the prepared reagent RBC evaluated in three batches ensured the
      quality and performance, and decreased the variance between different batches of
      the products to the utmost. In conclusion, the quality control problems of
      prepared reagent RBC had been solved and the accuracy of detection for blood
      types also elevated.

PMID- 18088487
TI  - [Analysis of prognostic correlated factors of 49 patients with mucosa-associated
      lymphoid tissue lymphoma].
AB  - The aim of this study was to investigate the clinical feature of mucosa
      associated lymphoid tissue lymphoma and clarify the relationship between the
      pathological, clinical features, the expression of API2-MALT1 and the prognosis.
      A number of factors including pathological characters, grade, stage, prognosis
      and treatment of 49 cases of MALT lymphoma were analyzed, and the API2-MALT1
      rearrangement was detected by RT-PCR. The results showed that 49 patients were
      diagnosed as MALT lymphoma, in which median age was 52.4 years. The percentage of
      patients older than 50 years was 67.3%. The majority of tumors were found in
      stomach (22 cases), intestine (13 cases), thyroid (6 cases) and so on. Among 49
      patients, stage I, II was 77. 6%, stage III, IV was 22.4%. API2-MALT1
      rearrangement were found 38.1% in low grade, and 12.5% in transform type. Among
      18 patients with gastric MALT lymphoma, 9 cases (50.0%) were helicobacter pylori
      (HP) positive and received antibiotic treatment. The 3 years overall survival was
      93.8%. It is concluded that MALT lymphoma is often seen in older patients, most
      of them were in low grade with slow progression. The site, grade, stage and
      molecular genetic changes are important prognostic factors, which can contribute
      to choosing suitable treatment for patients with MALT lymphoma. The antibiotic
      treatment is effective for patients with positive HP.

PMID- 18088488
TI  - [Effects of FLAG protocol in treatment of the first time induced non-remission
      acute myeloid leukemia].
AB  - In order to evaluate the efficacy of FLAG protocol (fludarabine, cytosine
      arabinoside and granulocyte colony-stimulating factor) in treatment of the first
      time induced non-remission acute myeloid leukemia (AML), 19 patients with first
      time induced non-remission acute myeloid leukemia were treated with FLAG
      protocol. The results showed that out of the 19 patients 13 patients obtained
      complete remission (CR) and the CR rate was 68.4%, 2 patients obtained partial
      remission (PR) and the PR rate was 10.5%, the overall remission rate was 78.9%.
      Among the patients in CR 5 patients had been received allogeneic stem cell
      transplantation, 3 patients from them survived without disease, including 1
      patient has survived 26 months and still remains in CR. Main toxicities of this
      protocol were gastrointestinal side effects, myelosuppression and neutropenia,
      slight abnormality of liver function and so on. It is concluded that the FLAG
      protocol should be employed for the the first time induced non-remission patients
      as early as possible, and provides conditions for the hematopoietic stem cell
      transplantation.

PMID- 18088489
TI  - [Analysis on prognosis and correlative factors of acute nonlymphocytic leukemia].
AB  - To analyze the prognosis and risk factors of acute nonlymphocytic leukemia
      (ANLL), 94 patients with acute nonlymphocytic leukemia were enrolled in this
      study, while survival rate and risk factors of prognosis were analyzed. The
      results indicated that the complete remission (CR) ratio was 51.1%. Overall
      survival and event-free survival rates of month 6, 12, 18, 24 were 68.6%, 55.8%,
      53.8%, 46.4%, 21.3% and 57.9%, 38.6%, 33.3%, 31.6%, 0% respectively. The factors
      such as age<40 years, WBC<10.0x10(9)/L before chemotherapy, WBC in the period of
      bone marrow suppression<1.0x10(9)/L, chemotherapy within 1 month after occurrence
      of leukemia, blood transfusion before chemotherapy of APL had favourable
      influence on remission and survival rates of ANLL patients. CR1, the time to get
      CR, length of CR and relapse significantly correlated with prognosis (p<0.05). It
      is concluded that the individualized therapy concerning the risk factors should
      be applied to ANLL patients for improving the remission, survival rate and
      prognosis.

PMID- 18088490
TI  - [Prognostic significance of lactate dehydrogenase and beta2-microglobulin in
      chronic lymphocytic leukemia].
AB  - To evaluate the prognostic value of lactate dehydrogenase (LDH) and beta2
      microglobulin (beta2-MG) in chronic lymphocytic leukemia (CLL), a total of 141
      cases of CLL had been investigated retrospectively. The Kaplan-Meier method was
      used to estimate the overall and failure-free survival distributions. Cox
      regression was used in univariate and multivariate analysis of potential
      predictors for overall survival. In multivariate analysis, the expression levels
      of LDH and beta2-MG were divided into 3 groups: (1) elevation of both LDH and
      beta2-MG levels; (2) elevation of LDH or beta2-MG levels alone; (3) normal levels
      of both LDH and beta2-MG. The results showed that serum LDH and beta2-MG levels
      of patients in Binet C were significantly higher than those in Binet A (p=0.034
      and p=0.035). The level of serum beta2-MG was not correlated with lymphocyte
      count (p=0.756). Binet C and high LDH level were associated with significantly
      shorter overall survival. beta2-MG was not proved to have any association with
      overall survival. The overall survival time in group of elevation of both LDH and
      beta2-MG levels was shorter than that in group of normal levels of both LDH and
      beta2-MG. It is concluded that serum LDH level and Binet stage are important
      prognostic factors for CLL.

PMID- 18088491
TI  - [A case of acute promyelocytic leukemia with double ider (17q-)].
AB  - This study reported a relapsed case of acute promyelocytic leukemia with complex
      chromosomal aberrations of double ider (17q-) and explored its laboratory and
      clinical features. Immunophenotypic analysis was performed by multiparameter flow
      cytometry. Conventional cytogenetics was used for karyotyping analysis.
      Fluorescence in situ hybridization (FISH) and multiplex fluorescence in situ
      hybridization (M-FISH) were also used to identify the chromosomal aberrations.
      The results demonstrated that karyotype was 47, XY, 1p-, 15q+, ider (17q)x2, FISH
      showed five fusion signals in a same interphase cell, and M-FISH confirmed the
      abnormalities. Immunophenotypic analysis showed positive expression of CD13 and
      CD33, while no expression of CD34, HLA-DR, or T, B lymphocyte markers. In
      conclusion, double ider (17q-) is a rare additional abnormality in APL patients;
      combination of FISH with M-FISH techniques is a reliable way to identify such
      complicated chromosomal aberrations.

PMID- 18088492
TI  - [Osteoclasts take part in modulation for bone marrow hematopoietic
      microenvironment--review].
AB  - Bone marrow hematopoietic microenvironment occupies the medullary cavities of
      bones throughout the skeleton and provides support for hematopoiesis and immune
      cells development. Bone-resorbing osteoclasts in bone marrow environment are
      specialized cells derived from the hematopoietic stem cells and play a pivotal
      role in process termed as bone remodeling that involves break down and build-up
      of bone. It is only recently that studies have provided a novel basis for
      understanding potential role of osteoclasts in homeostasis, stress-induced
      mobilization of hematopoietic progenitors and osteoimmunology. Further
      exploration on the interaction of osteoclasts with others in bone marrow
      hematopoietic microenvironment may contribute to future clinical treatments for
      hematopoietic and bone-related immunologic disorders including cancer. In this
      review the origin and identification of osteoclasts and regulation of mobilizing
      hematopoietic stem cells, as well as osteoclasts and osteoimmunity were mainly
      concerned.

PMID- 18088493
TI  - [Regulation of immunity by sphingosine 1-phosphate and its G protein-coupled
      receptors--review].
AB  - Sphingosine 1-phosphate (S1P) is an important biologically active
      lysophospholipid that transmits signals through a family of G-protein-coupled
      receptors (GPCRs) to regulate the vital functions of several types of immune
      cells. The S1P GPCRs suppress both generation of specialized functional
      cytokines, such as IFN-gamma and IL-4, and proliferation of T-cells. Although S1P
      is chemotactic to T cells, B cells, dendritic cells, and natural killer cells,
      the major effect of S1P on the immune system is the regulation of lymphocyte
      recirculation and tissue distribution by S1P and S1P1. Chemotactic response of
      CD4+CD25+ regulatory T cells to S1P is reduced, but its optimal suppressive
      activities require S1P. FTY720, a new class of immunomodulator, is rapidly
      phosphorylated by sphingosine kinase 2 in vivo to form the biologically active
      phosphorylated-FTY720 (FTY720-P), which closely resembles S1P. The FTY720-P is a
      true agonist for S1P1, S1P3, S1P4, and S1P5, it affects the tissue distribution
      and functional activity of T cells, B cells, dendritic cells and regulatory T
      cells. FTY720 were demonstrated to be a hypotoxic, great effective and reversible
      immunosuppressive efficacy to prevent allograft rejection and treat some
      autoimmune diseases. In this article, the synthesis and metabolism of S1P, the
      expression of S1P GPCRs in immune cells, the effect of S1P on immune cells, the
      drugs targeted to S1P GPCRs and their clinical implications are reviewed.

PMID- 18088494
TI  - [Resistance of leukemia cells to Fas/FasL-mediated apoptosis and strategies
      replying to antiapoptosis of leukemia cells--review].
AB  - At angle of cell apoptosis, the excessive less of hematopeitic cell apoptosis is
      a reason of hematopoietic cell accumulation. The Fas/FasL system as an important
      pathway inducing cell apoptosis participates in occurrence and development of
      leukemia. Leukemia cells generally are not sensitive or are resistant to Fas/FasL
      mediated apoptosis, while it is one of important reasons resulting in
      immunoescape and unsensitivity of leukemia cells to chemotherapy. In recent years
      studies related to mechanisms of leukemia cell resistance to Fas/FasL-mediated
      apoptosis such as Fas and FasL mutation and expression abnormality, Fas signaling
      transduction pathway abnormality, and regulatory affect of apoptotic regulatory
      genes on Fas/FasL system, as well as strategies replying to antiapoptosis of
      leukemia cells including NF-kappab, XIAP, membrane receptor CD28 and matrix
      metalloproteinase 7 obtained some progresses. The above-mentioned issues were
      reviewed in this article.

PMID- 18088495
TI  - [New insight into pathogenesis of idiopathic myelofibrosis--review].
AB  - Idiopathic myelofibrosis is a type of chronic myeloproliferative disorders
      characterized by splenomegaly, a leukoerythroblastic blood picture, teardrop
      poikilocytosis, in various degrees of bone marrow fibrosis and extramedullary
      hematopoiesis. In this paper, the biological characters and pathogenesis of
      idiopathic myelofibrosis such as mutation of tyrosine kinase receptor, mutation
      of GABA transporter 1, JAK2 mutation and c-MPl mutation, as well as other
      pathogenesis related with idiopathic myelofibrosis were reviewed.

PMID- 18088496
TI  - [Progression of foundational and clinical studies on use of arsenic trioxide in
      treatment of lymphoma--review].
AB  - Arsenic trioxide has been used to treat lymphoma experimentally since it was used
      to treat acute promyelocytic leukemia successfully. Massive works in this field
      have been done throughout the world. It was found that arsenic trioxide exerted
      an anti-lymphomatic effect via many pathways, and many substances could increase
      or reduce this effect. Arsenic trioxide can be used to treat relapsed and
      refractory lymphomas resistant to other chemotherapies with some therapeutic
      effects and limited side effects, which indicates that arsenic trioxide is a new
      potential drug for lymphoma. This article is an overview about these foundational
      and clinical studies.

PMID- 18088497
TI  - [Research on mechanism underlying bone damage in myeloma--review].
AB  - Multiple myeloma (MM) is a B cell malignancy characterized by enhanced bone loss
      that commonly associated with diffuse osteopenia, focal lytic lesions, pathologic
      fractures, and bone pain. The key mechanism of bone damage in myeloma is the
      abnormal regulation in bone metastasis, with increased osteoclast function and
      decreased osteoblast activity. This article reviewed the factors implicated, such
      as receptor activator of nuclear factor-kappaB (RANK), receptor activator of
      nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), macrophage
      inflammatory protein-1alpha (MIP-1alpha), SDF-1 and Wnt pathway. Further
      understanding of the regulation system of bone homeostasis helps to offer
      possible targets for future therapy.

PMID- 18088498
TI  - [Advance of study on mesenchymal stem cell homing--review].
AB  - Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells possessing multi
      differentiation potential, and were widely used in stem cell transplantation,
      tissue engineering, organ transplantation and immunotherapy, etc. However, the
      distribution and differentiation of MSCs after reinfusion directly influence
      their application. In this paper the "homing" characteristics, mechanisms and
      significance of MSCs were reviewed.

PMID- 18088499
TI  - The future of open- and closed-loop insulin delivery systems.
AB  - We have analysed several aspects of insulin-dependent diabetes mellitus,
      including the glucose metabolic system, diabetes complications, and previous and
      ongoing research aimed at controlling glucose in diabetic patients. An expert
      review of various models and control algorithms developed for the glucose
      homeostasis system is presented, along with an analysis of research towards the
      development of a polymeric insulin infusion system. Recommendations for future
      directions in creating a true closed-loop glucose control system are presented,
      including the development of multivariable models and control systems to more
      accurately describe and control the multi-metabolite, multi-hormonal system, as
      well as in-vivo assessments of implicit closed-loop control systems.

PMID- 18088500
TI  - Dosage plan of a flurbiprofen injection product using inhibition of protein
      binding by lipid emulsion in rats.
AB  - Flurbiprofen-axetil (FP-ax), a bolus injection product of a non-steroidal anti
      inflammatory drug (NSAID), is a prodrug of flurbiprofen, an NSAID. As
      flurbiprofen strongly binds to site II of human serum albumin (HSA), the free
      (unbound) concentration of flurbiprofen after injection of FP-ax is low. We have
      examined the inhibitory effect of free fatty acid (FFA), a binding inhibitor for
      site II of HSA, on the binding of flurbiprofen in-vitro and in-vivo by
      ultrafiltration, to establish an effective dosage of FP-ax. In-vitro, fatty acid
      mixtures (FAs) inhibited the binding of flurbiprofen to rat serum albumin. The
      free fraction of flurbiprofen was remarkably increased by FAs in rat serum. In
      vivo, FP-ax was injected into a control group (low FFA concentration in serum)
      and a lipid emulsion group (high FFA concentration in serum). The area under the
      curve of the free concentration of flurbiprofen during the alpha phase and the
      distribution volume of the central compartment of flurbiprofen were significantly
      higher in the lipid emulsion group than the control group (5.0- and 1.2-times,
      respectively). When FP-ax was administered at high FFA concentration, the free
      concentration of flurbiprofen and distribution of flurbiprofen to tissues
      increased transiently. This administration method may be useful for patients with
      cancer pain, having a potent analgesic effect.

PMID- 18088501
TI  - Toxicity and gut associated lymphoid tissue translocation of polymyxin B orally
      administered by alginate/chitosan microparticles in rats.
AB  - Fluorescent calcium alginate/chitosan microparticles, prepared using a spray
      drying technique followed by crosslinking reactions with calcium ions and
      chitosan, were assayed in-vivo for polymyxin B (PMB) oral toxicity, uptake by
      Peyer's patches and PMB oral absorption. A single PMB dose (300 mg kg(-1)),
      loaded in microparticles or dissolved in water, was administered to rats by oral
      gavage under fasted and fed conditions. By monitoring incidence of mortality,
      animal behaviour, clinical signs and abnormality in several organs, PMB in water
      solution was found lethal at a dose lower than the LD50 (790 mg kg(-1)) in the
      fasted state and toxic for the gastrointestinal tract in the fed state. However,
      no signs of acute toxicity at the level of the gastrointestinal tract were
      observed when animals were administered PMB loaded in microparticles under fasted
      and fed conditions. A lower PMB dose (125 mg kg(-1)), loaded in microparticles or
      dissolved in water, was given to rats in a fed state to determine PMB levels in
      Peyer's patches, urine and serum as well as to detect the loaded microparticles
      inside Peyer's patches for three days after dosing. Abnormalities were observed
      at gut level only when PMB was dosed in a water solution. Detectable antibiotic
      levels in Peyer's patches and urine as well as more constant PMB serum
      concentrations were provided by dosing PMB loaded in microparticles. Therefore,
      the use of alginate/chitosan microparticles to target the lymphatic system could
      improve safety when administering PMB orally.

PMID- 18088502
TI  - Synergistic effect of iontophoresis and soluble microneedles for transdermal
      delivery of methotrexate.
AB  - The aim of this study was to investigate the transdermal iontophoretic delivery
      of methotrexate, alone or in combination with microneedles, in-vitro and in-vivo
      using intracutaneous microdialysis in the hairless rat. The average depth of the
      microdialysis probe in the skin was found to be 0.54 mm. Methotrexate was stable
      in the presence of an applied electric field as determined by cyclic voltammetry.
      A current density of 0.4 mA cm(-2) applied for 60 min was used in combination
      with maltose microneedles to enhance delivery of methotrexate across the skin.
      Delivery was enhanced by iontophoresis and microneedles, both in-vitro and in
      vivo. A synergistic 25-fold enhancement of delivery was observed in-vivo when a
      combination of microneedles and ionto- phoresis was used compared with either
      modality alone.

PMID- 18088503
TI  - In-vitro and in-vivo studies of pectin/ethylcellulosefilm-coated pellets of 5
      fluorouracil for colonic targeting.
AB  - The aim of the present study was to define in-vitro and in-vivo characteristics
      of pectin/ethylcellulose-film-coated pellets of 5-fluorouracil (5-FU) for colonic
      targeting. The pellet cores were coated to different film thicknesses with three
      different pectin/ethylcellulose formulations using a fluidized bed coater. The
      gastrointestinal (GI) transit of coated pellets was determined by counting the
      percentage of coated pellets in the GI lumen by celiotomy at certain times after
      oral administration. 5FU was administered to rats at a dose of 15 mg kg(-1). The
      toxicity of 5-FU in the GI tract was evaluated using histological examination.
      The 1:2 ratio pectin:ethylcellulose-coated pellets with 30% total weight gain
      (TWG-30%) produced more satisfactory drug-release profiles in the simulated
      gastric, intestinal and colonic fluids. Most of the coated pellets were
      eliminated from the stomach in 2 h, moved into the small intestine after 2-4 h,
      and reached the large intestine after 4 h. After oral administration of coated
      pellets, 5-FU started appearing in the plasma at 7 h, and reached peak plasma
      concentration (Cmax) of 3.21+/-2.01 microg mL(-1) at 16 h (Tmax); the Cmax for
      uncoated pellets was 22.21+/-2.60 microg mL(-1) at Tmax 0.75 h. The TWG-30%
      formulation showed delayed Tmax, decreased Cmax and prolonged mean residence time
      compared with uncoated pellets. Marked pathological features in the colon were
      seen in rats given coated pellets, but no injuries were observed in the upper GI
      tract. The formulation of TWG-30% could deliver 5-FU to the colon for local
      action.

PMID- 18088504
TI  - Effects of CYP inducers and inhibitors on the pharmacokinetics of intravenous
      theophylline in rats: involvement of CYP1A1/2 in the formation of 1,3-DMU.
AB  - The types of hepatic cytochrome P450 (CYP) isozymes responsible for the
      metabolism of theophylline and for the formation of 1,3-dimethyluric acid (1,3
      DMU) in rats in-vivo does not seem to have been studied at the dose ranges of
      dose-independent metabolic disposition of theophylline in rats (up to 10 mg kg(
      1)). Therefore, theophylline (5 mg kg(-1)) was administered i.v. to male Sprague
      Dawley rats pretreated with various inducers and inhibitors of CYP isozymes. In
      rats pretreated with 3-methylcholanthrene (3-MC), orphenadrine or dexamethasone
      (main inducers of CYP1A1/2, CYP2B1/2 and CYP3A1/2, respectively, in rats), the
      time-averaged non-renal clearance (CLNR) of theophylline was significantly faster
      than in their respective controls (1260, 42.7 and 69.0% increases, respectively).
      However, in rats pretreated with troleandomycin (a major inhibitor of CYP3A1/2 in
      rats), CLNR was significantly slower than in the controls (50.7% decrease). The
      24 h urinary excretion of 1,3-DMU was increased significantly only in rats
      pretreated with 3-MC. The ratio of area under the curve for 1,3-DMU and
      theophylline (AUC1,3-DMU/AUCtheophylline) was increased significantly in rats
      pretreated with 3-MC (160% increase) and decreased significantly in rats
      pretreated with troleandomycin (50.1% decrease); however, the ratio was not
      increased in rats pretreated with dexamethasone. These data suggest that
      theophylline is primarily metabolized via CYP1A1/2, CYP2B1/2, and CYP3A1/2, and
      that 1,3-DMU is primarily formed via CYP1A1/2, and possibly CYP3A1/2, in rats.

PMID- 18088505
TI  - Involvement of Mrp2 (Abcc2) in biliary excretion of moxifloxacin and its
      metabolites in the isolated perfused rat liver.
AB  - Moxifloxacin is a novel antibacterial agent that undergoes extensive metabolism
      in the liver to the glucuronide M1 and the sulfate M2, which are eliminated via
      the bile. To investigate the role of the multidrug resistance-associated protein
      (Mrp2) as the hepatic transport system for moxifloxacin and its conjugates,
      livers of Wistar and Mrp2-deficient TR- rats were perfused with moxifloxacin (10
      microM) in a single-pass system. Values for the hepatic extraction ratio (E) and
      clearance (Cl) were insignificantly higher in TR- rats than Wistar rats (0.193+/
      0.050 vs 0.245+/-0.050 for E; 6.85+/-1.96 vs 8.73+/-1.82 mL min(-1) for Cl),
      whereas biliary excretion and efflux into perfusate over 60 min were
      significantly lower in the mutant rat strain. Cumulative biliary excretion of M1,
      M2 and moxifloxacin was significantly reduced to 0.027%, 19.1%, and 29.6% in the
      TR- rats compared with Wistar rats, indicating that the biliary elimination of M1
      is mediated exclusively by Mrp2, whereas that of M2 and moxifloxacin seems to
      depend mostly on Mrp2 and, to a smaller extent, a further unidentified
      canalicular transporter. Moxifloxacin stimulates bile flow by up to 11% in Wistar
      rats, but not in TR- rats, further supporting an efficient transport of this drug
      and its glucuronidated and sulfated metabolites by Mrp2. Moxifloxacin (10 microM)
      also reversibly inhibited the Mrp2-mediated biliary elimination of
      bromsulphthalein in Wistar rats by 34%, indicating competition with the
      elimination of Mrp2-specific substrates. In conclusion, we found that Mrp2
      mediates the biliary elimination of moxifloxacin and its glucuronidated and
      sulfated metabolites in rats. MRP2 may therefore play a key role in the transport
      of moxifloxacin and its conjugates into bile in humans.

PMID- 18088506
TI  - Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and
      implications for in-vivo experiments.
AB  - To use rodent models effectively in in-vivo investigations on oral drug and
      vaccine delivery, the conditions in the gastrointestinal tract must be
      understood. Some fundamental information is currently unavailable or incomplete.
      We have investigated the pH, water content and lymphoid tissue distribution along
      the gastrointestinal tract, as well as the stomach volume, as these were critical
      to our investigations on pH-responsive drug delivery and colonic vaccination. The
      observed values were compared with those in man as an indication of the validity
      of the rodent model. The mouse stomach pH was 3.0 (fed) and 4.0 (fasted), and the
      corresponding values in the rat were 3.2 (fed) and 3.9 (fasted). The mean
      intestinal pH was lower than that in man (<pH 5.2 in the mouse; <pH 6.6 in the
      rat). This brings into question the use of rodents in investigations on enteric
      coated drug carriers targeted to the large intestine/distal gut. The water
      content in the gastrointestinal tract in the fed and fasted mouse was 0.98+/-0.4
      and 0.81+/-1.3 mL, respectively, and in the fed and fasted rat was 7.8+/-1.5 and
      3.2+/-1.8 mL. When normalized for body weight, there was more water per kg body
      weight in the gastrointestinal tracts of the mouse and rat, than in man. The
      stomach capacity was found to be approximately 0.4 and 3.4 mL for mice and rats,
      respectively. The low fluid volume and stomach capacity have implications for the
      testing of solid dosage forms in these animal models. Substantial amounts of
      lymphoid tissue analogous to small intestinal Peyer's patches were measured in
      the rat and mouse colon, showing the feasibility of colonic vaccination, a route
      which might prove to have different applications to the more commonly studied
      oral vaccines. The existence of lymphoid tissue in the mouse and rat caecum has
      also been reported.

PMID- 18088507
TI  - Percutaneous penetration of felbinac after application of transdermal patches:
      relationship with pharmacological effects in rats.
AB  - We have evaluated the percutaneous penetration of felbinac following application
      of topical patches using a microdialysis technique, and have examined
      correlations with pharmacological effects. A linear microdialysis probe with a 20
      mm dialysis fibre was inserted into the skin of anaesthetized rats. Probe
      perfusion was started at 2.0 microL min(-1) with physiological saline and after a
      60-min baseline sampling of dialysate, 0.1 mL croton oil was applied to the skin
      surface at a concentration of 8%, v/v. A felbinac patch was then applied to the
      same point 60 min thereafter and dialysate was sampled at 60-min intervals up to
      300 min after patch application, for determination of concentrations of felbinac
      and prostaglandin (PG) E2. Analgesic effects of felbinac patches in an
      iodoacetateinduced osteoarthritis model and an incisional pain model were
      evaluated using the weight bearing method. After application of patches, felbinac
      penetration into the skin was rapid, maximum concentrations in the dialysates
      with 0.07, 0.5 and 3.5% w/w felbinac patches being 0.046+/-0.02, 0.104+/-0.06 and
      0.244+/-0.2 microg mL(-1), respectively. Dermal administration of croton oil
      caused an increment in PGE2 levels, which was significantly decreased by 0.5 and
      3.5% felbinac patches 2-5 h after application. In pharmacological studies, 3.5%
      felbinac patches suppressed pain-associated behaviour induced by iodoacetate
      injection and plantar incision. These results suggested that the transdermal
      patch containing 3.5% felbinac may become a useful formulation.

PMID- 18088508
TI  - Semi-mechanistic description of the in-vitro antiproliferative effect of
      different antitumour agents.
AB  - The aim of the present work was to describe the antiproliferative effect of
      camptothecin (CPT), topotecan (TPT) and cisplatin (CIS) in cultured cells using a
      semi-mechanistic pharmacodynamic approach. This effect on the growth of DHD
      K12PROb cells was modelled as a function of drug concentration and time of
      exposure using the Gompertz framework. Models reflected two major processes: cell
      proliferation and cell death/degradation. Antiproliferative effect of CPT and TPT
      was described as inhibition of cell proliferation, while the effect of CIS was
      described as stimulation of cell death, including a signal transduction process,
      reflected as a delay in the onset of drug action. The half-life associated with
      such a transduction process was estimated to be approximately 27 h.
      Interestingly, the time profiles of the model predicted a signal transduction
      process that closely resembled the observed profiles of caspase-3, a protein
      implicated in CIS-mediated apoptosis. Therefore, the combination of a simple and
      sensitive design, together with an appropriated modelling strategy, allowed us to
      explore different mechanisms of action for antitumour agents in cultured cells
      and to obtain information about the dynamics of signal transduction and the
      potential use of biomarkers.

PMID- 18088509
TI  - Turmeric-based diet can delay apoptosis without modulating NF-kappaB in
      unilateral ureteral obstruction in rats.
AB  - The unilateral ureteral obstruction (UUO) model of renal injury in rat is
      characterized by nuclear factor kappaB (NF-kappaB) activation and tumour necrosis
      factor alpha (TNF-alpha) production, which induces apoptosis via activation of
      caspase 8 resulting in cell death. Curcumin, the major component found in
      turmeric spice, has been reported to provide protection against fibrosis and
      apoptosis elicited by UUO. This study examined the effects of a turmeric-based
      diet (5% w/w) on the apoptotic pathway induced by UUO in rats after 30 days of
      ligation. Administration of a turmeric-based diet demonstrated a significant
      decrease (P<0.05) in mRNA expression of TNF-alpha and caspase 8, but not NF
      kappaB, expression, which may contribute to the protective role of the turmeric
      based diet. We conclude that a turmeric-based diet can delay apoptosis without
      modulating NF-kappaB, so as not to sensitize the mesangial cells to the apoptotic
      stimuli.

PMID- 18088510
TI  - The anti-diabetic effects and pharmacokinetic profiles of
      bis(maltolato)oxovanadium in non-diabetic and diabetic rats.
AB  - The purpose of this study was to evaluate the anti-diabetic effects and
      pharmacokinetics of bis(maltolato)oxovanadium (BMOV) in rats. The anti-diabetic
      study was carried out in non-diabetic and diabetic rats by single-dose
      subcutaneous and intragastric administration. Pharmacokinetic investigation was
      performed using non-diabetic rats. Results showed that BMOV significantly
      decreased plasma glucose levels in diabetic rats at all given doses, and restored
      hyperglycaemic values to normal values after subcutaneous injections at doses of
      4 and 8 mg vanadium (V)/kg or after intragastric administration at doses of 14
      and 28 mgV/kg, respectively, but did not affect the plasma glucose level in non
      diabetic rats. BMOV could be rapidly absorbed, slowly eliminated from plasma,
      widely distributed in various tissues and accumulated to a greater extent in the
      femur tissue. The average absolute bioavailability for intragastric
      administration at a single dose of 3, 6 and 12 mgV/kg was 28.1%, 33.7% and 21.4%,
      respectively. The presence of the peak vanadium level in the plasma was not
      coincident with that of the maximum effect of lowering plasma glucose levels. In
      conclusion, at the present dosing levels and administration routes, BMOV was
      effective in lowering plasma glucose levels in diabetic rats. BMOV has a
      promising outlook as an oral glucose-lowering drug.

PMID- 18088511
TI  - Optimization and validation of a chromatographic method for the simultaneous
      quantification of six bioactive compounds in Rhizoma et Radix Polygoni Cuspidati.
AB  - A reverse-phase HPLC method was developed for simultaneous quantification of six
      bioactive compounds in Rhizoma et Radix Polygoni Cuspidati. These compounds-
      polydatin (1), resveratrol (2), rhein (3), emodin (4), chrysophanol (5) and
      physcion (6)--were analysed from 24 authentic samples of the herb using UV HPLC.
      Based on the UV absorption characteristics of the six compounds, absorption
      wavelengths of 306 nm were chosen to quantify compounds 1 and 2, and 290 nm for
      compounds 3-6. A reliable and reproducible quantitative HPLC method for analysing
      authentic samples of Rhizoma et Radix Polygoni Cuspidati from different
      cultivation regions was developed. The results showed that the concentration of
      compound 1 in samples from Sichuan was almost 2 fold higher than that of samples
      acquired in Guangxi. Furthermore, compounds 3 and 5 were not found in all the
      samples tested. Thus, instead of using polydatin (1) and emodin (4) as markers
      for quality assessment, as in conventional practice, these findings show that
      compounds 2 and 6 are more suited to act as marker compounds for a more specific
      assessment of the quality of this herb.

PMID- 18088512
TI  - Protective effects of hydroxysafflor yellow A on acute and chronic congestive
      cardiac failure mediated by reducing ET-1, NOS and oxidative stress in rats.
AB  - The present study was conducted to investigate whether hydroxysafflor yellow A
      (HSYA) has a protective effect on acute and chronic heart failure (AHF/CHF)
      induced by ligation of the left anterior descending coronary artery for 3 h and 8
      weeks, respectively. The rats were divided into the following groups: sham
      operation, coronary artery ligation (CAL), CAL+HSYA (100 mg kg(-1) by gavage) and
      CAL+diltiazem (20 mg kg(-1) by gavage). In the AHF model, heart function, as
      determined by haemodynamic studies and echocardiography, was improved
      significantly by pretreatment with HSYA or diltiazem. Significant reductions in
      elevated serum creatine phosphokinase, lactate dehydrogenase, malondialdehyde
      (MDA), glutamic oxalacetic transaminase, glutamic pyruvic transaminase and blood
      viscosity were observed, and the activity of serum superoxide dismutase (SOD) was
      enhanced (all P<0.01). In the CHF model, HSYA and diltiazem restored abnormal
      heart function, and completely suppressed the elevated plasma atrial natriuretic
      polypeptide (ANP) and endothelin-1 (ET-1), serum and left-ventricular tissue
      inducible nitric oxide (NO) synthase (iNOS), NO and MDA, and improved the
      decrease in SOD. HSYA and diltiazem improved cardiac performance in AHF and
      reduced cardiac remodelling in CHF by reducing tissue weight indices: left
      ventricular weight/body weight (BW), right ventricular weight/BW, kidney
      weight/BW and lung weight/BW, and attenuating increases in infarct size, inner
      diameter of the left ventricle and collagen volume fraction in non-infarcted
      areas, and the decrease in mean wall thickness of infarcted myocardium. These
      results suggest that HSYA exerted beneficial actions in cardiac performance in
      models of both AHF and CHF, mainly by suppressing ET-1, iNOS and oxidative stress
      in infarcted tissue.

PMID- 18088513
TI  - Pharmacokinetics of formulated tenoxicam transdermal delivery systems.
AB  - To investigate the feasibility of developing a new tenoxicam transdermal delivery
      system (TDS), the pharmacokinetics of tenoxicam from various formulated TDS were
      evaluated and compared with values following oral administration of tenoxicam and
      with application of a piroxicam plaster (Trast) marketed in Korea. Based on
      previous in-vitro study results, a mixture of diethylene glycol monoethyl ether
      (DGME) and propylene glycol monolaurate (PGML) (40:60) was used as a vehicle, and
      caprylic acid, capric acid, lauric acid, oleic acid or linoleic acid (each at 3%)
      was added as an enhancer. Triethanolamine (5%) was used as a solubilizer, and
      Duro-Tak 87-2510 as a pressure-sensitive adhesive. Among these fatty acids used
      for the formulation of tenoxicam TDS, caprylic acid showed the greatest enhancing
      effect; the area under the plasma concentration-time profile (AUC) decreased in
      the order of caprylic acid>linoleic acid>or=oleic acid>lauric acid>capric acid.
      Compared with oral administration, maximum plasma concentration (Cmax) was
      significantly lower, and time to reach Cmax (Tmax) delayed with all formulated
      tenoxicam TDS. All formulated TDS resulted in a lower AUC than with the oral
      formulation, except for TDS containing caprylic acid, although the difference was
      statistically significant only with capric acid. The AUC for all the formulated
      tenoxicam TDS was significantly higher than that of the piroxicam plaster; TDS
      with caprylic acid increased AUC 8.53-fold compared with the piroxicam plaster.
      Even though the Tmax of tenoxicam TDS was not significantly different from that
      of the piroxicam plaster, Cmax was higher; formulations containing caprylic acid
      and linoleic acid increased Cmax by 7.39- and 8.76-fold, respectively. In
      conclusion, a formulation containing 1.5 mL DGME-PGML (40:60) with 3% caprylic
      acid and 5% triethanolamine mixed with 6 g Duro-Tak 87-2510 could be a good
      candidate for developing a new tenoxicam TDS to maintain a comparable extent of
      absorption to oral delivery while attaining a prolonged effect with fewer toxic
      events.

PMID- 18088514
TI  - Discarded human spermatozoa, eggs and embryos for personnel training and practice
      in assisted reproduction.
AB  - An ethical issue that has been largely overlooked is the use of discarded human
      gametes and embryos for personnel training in clinical assisted reproduction
      technology, e.g. intracytoplasmic sperm injection and preimplantation genetic
      diagnosis. Unlike experimental research for generating peer-reviewed journal
      publications and intellectual property, there is no similar paper trail or
      smoking gun if human gametes and embryos are utilized solely for personnel
      training without the patient's knowledge and consent. For many assisted
      reproduction laboratories in private practice that are not affiliated with
      research or academic institutions, there are often difficulties in procuring
      animal material for personnel training. In contrast, discarded human gametes and
      embryos are readily available and can be convenient for training inexperienced
      personnel in assisted reproduction techniques. Very often, only verbal consent is
      obtained from patients, without written documentation, and this situation can
      potentially lead to abuse. For example, fertility clinics and laboratories may
      conduct training courses and workshops for generating additional income and
      revenue; and there is a possibility of discarded human material being utilized
      for such profit-making ventures without patients' prior knowledge. Hence, it is
      the moral duty and obligation of international professional bodies to advocate
      and draft clearly defined regulatory guidelines and legislative framework for
      this purpose.

PMID- 18088515
TI  - The debate surrounding human embryonic stem cell research in the USA.
AB  - Despite its potential for reducing human suffering, the advancement of human
      embryonic stem cell research has not been given top priority by the US
      government, and the scientific community has been engaged in a debate on this
      issue in the USA and beyond. The central question in this debate is whether the
      promise of stem cells justifies the destruction of human embryos - mainly embryos
      that are surplus to the needs of patients undergoing infertility treatment. It is
      argued here that this debate belongs in the same category as the debates on
      global warming and evolution, because it has much in common with both. It is
      conducted with a heavy load of scientifically uninformed views and beliefs and
      framed largely by an implacable opposition with the aim of creating public
      confusion and doubt. It is primarily politically motivated and, as is true about
      the debate on evolution, it is rooted in religion. A human embryo is not a human
      being or person even if it is deserving of - and receives - respect and
      extraordinary care in the context of assisted human reproduction. Rather than
      engaging in a futile debate that clouds the way forward in a vital branch of
      biology, scientists ought to continue to emphasize the importance of human embryo
      research.

PMID- 18088516
TI  - Biological and evolutionary contributions to developmental sex differences.
AB  - Boys and girls, and men and women show consistent differences, on average, in
      interests, activity preferences, and social styles. This article summarizes sex
      differences in human development from infancy through the childhood years and
      considers how these differences in developmental patterns relate to human
      evolutionary history. Evidence is reviewed suggesting that the psychological
      traits that were advantageous differed consistently for men and women during
      human evolution, consistent with Darwin's (1871) sexual selection as a mechanism
      through which cognitive and behavioural sex differences evolve and develop during
      lifetimes. The result is that some sex differences are found very early in
      development in predispositions to engage in different activities, to attend to
      different social information, and in methods of social influence. These early
      differences, in turn, prepare children for somewhat different tasks and roles in
      adulthood. Although these differences have strong biological origins,
      developmental experiences serve to flesh out and elaborate on these differences,
      or to minimize them, depending on the demands of the culture in which the child
      is situated.

PMID- 18088517
TI  - Boy or girl: gender preferences from a Darwinian point of view.
AB  - This article reviews evolutionary biological studies of sex-biased post-natal
      parental investment that may be relevant to the issue of preconception gender
      selection. The focus is on tests of the Trivers-Willard hypothesis, which
      predicts that natural selection has favoured parents that bias investment in
      favour of the sex with the best reproductive prospects. Because resource
      abundance and scarcity often have greater effects on male than on female
      reproductive success, the Trivers-Willard model predicts that natural selection
      will most often favour parents who favour males when conditions are good and
      females when conditions are poor. Empirical tests of this hypothesis are mixed in
      terms of the appropriateness of their methods and their relevance to the model.
      Tests with more appropriate measures of such key variables as parental investment
      tend more often to provide support for the hypothesis. The implications of these
      findings for the issue of preconception gender selection are briefly discussed.

PMID- 18088518
TI  - Is preconception sex selection necessarily sexist?
AB  - The advent of sperm sorting opens up the possibility that sex selection could
      become much more easily accessible, raising many moral questions. Two fundamental
      issues are whether sex selection is necessarily sexist and whether it should be
      highly regulated or banned on those grounds. I argue that, in some societies, sex
      selection of males is clearly sexist and that it promotes and reinforces extreme
      sexism. Extreme sexism seriously harms women, and if, in the opinion of those who
      know the situation best, prohibition is the best strategy for protecting women, a
      ban can be reasonable. In other societies, there may not be a pronounced
      preference for males, and sex selection may be neither particularly harmful nor
      even sexist. In those cases, there is no obvious benefit from prohibition, and
      prohibition may even represent a risk to women's reproductive autonomy.

PMID- 18088519
TI  - Prenatal testing for adult-onset conditions: cui bono?
AB  - There is a widespread consensus in the medical and bioethical communities that
      minor children should not be tested for untreatable adult-onset genetic diseases.
      This paper looks at the implications for prenatal genetic testing. What is the
      purpose of such testing? Who is intended to benefit? Is it the prospective
      parents, to enable them to make informed reproductive decisions? Or society, by
      reducing the prevalence of genetic diseases? Or can prenatal testing for adult
      onset conditions be done 'for the sake of the child'? While the last
      justification, if plausible, would provide a better justification than the other
      two, it is not clear that even reproductive autonomy justifies prenatal genetic
      testing for untreatable adult-onset diseases. Nor can a rationale be provided by
      the other possibilities since neither society nor the future child is likely to
      be benefited by such testing.

PMID- 18088520
TI  - Are Catholic universities giving up reproductive medicine?
AB  - The Catholic Church has established a large number of universities worldwide. A
      dozen have schools of medicine and the impact of church doctrine on reproductive
      medicine appears widely disparate between some medical schools at Catholic
      universities in Europe and the rest of the world. The pressure of the Vatican on
      the Catholic universities in Belgium to abandon IVF is mounting. Comparison of
      the scientific performances by the Catholic universities with and without IVF
      shows that the absence of IVF is disastrous for research in reproductive
      medicine.

PMID- 18088521
TI  - Women's Health Initiative (WHI).

PMID- 18088522
TI  - A stronger case for calcium and vitamin D in fracture prevention.

PMID- 18088523
TI  - Changes in practice since the publication in 2007 of further results from the
      Women's Health Initiative and the Million Women Study.

PMID- 18088524
TI  - Risk management issues in postmenopausal health care.
AB  - As in other areas of clinical activity, unintended harm to patients may occur in
      the course of postmenopausal health care, and measures to ensure patient safety
      should be actively promoted. This paper discusses the application of some basic
      principles of risk management to postmenopausal health care. To facilitate
      communication and reduce errors in diagnosis and treatment, risk management
      should be incorporated in the development of a dedicated menopause service.

PMID- 18088525
TI  - Proteins' promise--progress and challenges in ovarian cancer proteomics.
AB  - Ovarian cancer is the leading cause of gynaecological cancer death. The mortality
      rate of ovarian cancer could be greatly decreased if there were a screening test
      which was able to detect the disease at an early stage, resulting in an increased
      probability of cure. The most promising prospect for the early detection of
      ovarian cancer comes from the rapidly advancing field of clinical proteomics. An
      increasing number of reports on the potential clinical application of proteomics
      research for early detection as well as risk assessment and management of ovarian
      cancer are being published. Although the research is very promising, major
      technical challenges are still preventing new discoveries in ovarian cancer
      proteomics from being translated into clinical practice.

PMID- 18088526
TI  - An evidence-based approach to lifestyle interventions in urogynaecology.
AB  - Urinary incontinence, urgency, overactive bladder symptoms, cystitis and urinary
      tract infections are common conditions that collectively trouble over one-third
      of the female population around and beyond the time of menopause, with a
      detrimental effect on physical, social and mental wellbeing. Apart from
      pharmacological and surgical treatments, a long list of lifestyle, behavioural,
      physical and complementary interventions have been introduced over the years to
      relieve lower urinary tract symptoms. This review examines the effect on these
      symptoms of lifestyle factors (such as weight, smoking, dietary components, fluid
      intake, exercise and bowel habit), complementary therapies (such as herbal
      remedies, acupuncture and hypnotherapy), behavioural therapies (bladder training
      and timed and prompted voiding), pelvic floor muscle training and some over-the
      counter preparations. The high prevalence of the above conditions in combination
      with the increasing publicity for and awareness of the subject has contributed to
      the popularity of the interventions considered in this review. Many of them,
      however, lack a solid evidence base with regard to their efficacy and few have
      been subjected to robust randomized trials. It is widely recognized that there is
      a need for further prospective interventional studies of all lifestyle
      interventions to evaluate the effects of modifying these factors on lower urinary
      tract symptoms.

PMID- 18088527
TI  - Treating cardiovascular disease in women.
AB  - Cardiovascular disease (CVD) is the most common cause of death in women but some
      of the challenges of management differ from those in men. This article addresses
      the gender-specific issues of cardiovascular management, with emphasis on
      ischaemic heart disease and modification of coronary risk factors. Women with
      ischaemic heart disease present later than men, and are therefore older and more
      likely to suffer from co-morbidities such as diabetes and hypertension. Proven
      CVD risk factors in women can be divided into those that are modifiable and those
      that are non-modifiable. The former include diabetes, dyslipidaemia,
      hypertension, smoking, obesity, sedentary lifestyle and poor nutrition; the
      latter include family history of heart disease and older age at presentation. It
      is this difference in age and general health that explains much of the
      variability in response to treatment. Pharmacotherapy, percutaneous intervention,
      surgical revascularization, and cardiac rehabilitation and disease prevention are
      discussed.

PMID- 18088528
TI  - Grape flavonoids and menopausal health.
AB  - Grape flavonoids are members of a larger group of plant compounds called
      polyphenols. Epidemiological evidence relating to the traditional Mediterranean
      diet, which is high in polyphenols, derived from vegetables and red wine,
      suggests that dietary polyphenols are of benefit to health and reduce the
      incidence of cardiovascular disease. Overall, the evidence is promising for the
      benefit of grape flavonoids in the form of red wine, red grape juice and related
      preparations for cardiovascular risk factors. There are data to suggest a
      reduction in platelet activation, inflammation and low-density lipoprotein
      oxidation, and improvement of endothelial function with grape flavonoids. The
      evidence for grape flavonoids and renal function, cognition and cancer is less
      clear. However, it is important to note that much of this research has been
      carried out in animal and cell models; relatively little work has been done in
      humans and specifically on the health of menopausal women. There are no general
      safety concerns with ingestion of grape products. Obviously, consumption of red
      wine should be within recommended limits and it should be noted that grape juice
      has high sugar content. Grape flavonoids are also available as a supplement. In
      conclusion, it is likely that grape flavonoids do benefit the menopausal women.
      Further research is needed on the mode and dosage of application to maximize
      these benefits.

PMID- 18088529
TI  - Predicting falls in older women.
AB  - Falls among older people are common and their occurrence is associated with
      detrimental effects on physical and psychosocial functioning. However, falls are
      not an inevitable consequence of ageing and there is growing evidence of
      effective interventions to prevent them. Accurate screening methods to identify
      high-risk populations are important if such strategies are to be cost-efficient.
      Epidemiological studies have identified a diverse group of risk factors for falls
      of different types in a variety of settings and patient groups. These have proved
      useful in delineating high-risk groups and have propagated a range of risk
      assessment tools for falls. Without an accepted taxonomy for the reporting of
      trials testing these instruments, direct comparison of results has been
      difficult. In frail older people, 'multi factorial assessment tools' have
      achieved some utility in the discrimination of fallers from non-fallers, whereas
      performance-based 'functional mobility assessments' appear to be more suited to
      predicting falls in groups of more active elders. The predictive value of these
      measures has been hampered by the complex and dynamic interaction between
      attendant risk factors and their variable influence in populations of different
      frailty profiles. Furthermore, current indices used in the prediction of falls
      are built upon statistical methodologies employing logistic regression, which
      fail to account for the breadth and depth of these associations in populations at
      risk of falling. Statistical representations more consistent with the complex
      modelling required in the design of falls risk assessment trials, such as tree
      classification techniques, may provide better results in future studies that aim
      to generate accurate predictors of falls.

PMID- 18088530
TI  - Prevention and treatment of osteoporosis in women.
AB  - Osteoporosis affects one in three women. There has been some confusion among
      women and health professionals about the management of osteoporosis since the
      publication of the Women's Health Initiative and Million Women studies. This
      guidance regarding estrogen-based and non-estrogen-based treatments for
      osteoporosis responds to the controversies about the benefits and risks of
      individual agents. Treatment choice should be based on up-to-date evidence and
      targeted to individual women's needs.

PMID- 18088531
TI  - Suppression of cyclical ovarian function in the treatment of severe premenstrual
      syndrome.

PMID- 18088532
TI  - Bleeding with menopausal hormone therapy: physiological or pathological?
AB  - Abnormal bleeding is a common reason for discontinuation of hormone replacement
      therapy. There is little consensus regarding when to investigate abnormal
      bleeding, what to do about persistent bleeding or when reinvestigation is
      indicated. Transvaginal ultrasound, endometrial biopsy and hysteroscopy are
      discussed. The mechanisms of this bleeding are poorly understood and do not
      correlate well with endometrial histology or the type or dose of hormone therapy
      used. Endometrial bleeding requires breakdown of endometrial vessels and their
      overlying epithelium. Endometrial vascular breakdown appears to be largely
      locally regulated. Potential mechanisms involved in endometrial bleeding include:
      changes in the ratio of vascular endothelial growth factor (pro-angiogenic) to
      thrombospondin-1 (anti-angiogenic); alterations in matrix metalloproteinases and
      their tissue inhibitors; changes in endometrial haemostasis due to tissue factor;
      and increased endometrial leucocytes.

PMID- 18088548
TI  - Prolonged statin administration does not act on the cell-mediated immunity of HIV
      infected dyslipidemic patients treated with a steady and effective highly active
      antiretroviral therapy. A two-year prospective study of statin versus fibrate
      administration.
AB  - OBJECTIVE: To assess whether statin administration for HIV-associated
      hyperlipidemia has long-term effects on immune recovery (as expressed by the
      trend of mean CD4+ lymphocyte count), in patients on a virologically-active HAART
      regimen since 12 months or more. METHODS: Single-centre, open-label, prospective
      study of 301 hyperlipidemic patients treated with statins (99 cases, with a
      predominant hypercholesterolemia), fibrates (116 subjects, when
      hypertriglyceridemia prevailed), or a isolated dietary/exercise program (86
      patients, used as a control group). Neither epidemiological nor clinical,
      virological, or immunological differences were detected among the three study
      groups at baseline. During the subsequent follow-up, patients were excluded from
      evaluation should virological efficacy was not maintained, and/or initial
      hypolipidemic therapy was modified or interrupted for any reason. RESULTS: The
      quarterly assessment of mean CD4+ lymphocyte count did not disclose any
      statistically significant difference among the three study groups, since baseline
      and until at least 24 consecutive months of follow-up. Our data tend to exclude
      relevant in vivo negative activities of statins on immune system recovery of HIV
      infected individuals who undergo a virologically effective HAART treatment.
      CONCLUSIONS: Multiple, pleiotropic features have been attributed to both statins
      and fibrates, and also apparently significant effects on laboratory markers of
      HIV disease progression have been recently claimed or expected. Despite some
      preliminary in vitro and ex-vivo models, both the main hypolipidemic classes
      administered for the management of HIV-related dyslipidemia (both statins and
      fibrates) do not seem to act significantly on clinical immune response of
      patients successfully treated with HAART. Multifactorial pathways are expected to
      interact with the cell-mediated immune system of HIV-infected patients undergoing
      successful HAART, and further studies are needed to elucidate whether more subtle
      immune effects might be prompted by a long-term administration of hypolipidemic
      drugs in this speciasl setting.

PMID- 18088549
TI  - Genetic disregulation of TNF alpha and TNF alpha type II receptors in colon
      cancer at the II and III stage of disease.
AB  - The expression of the genes coding TNFalpha and TNF RII receptors (TNF RII: TNFR2
      membrane and soluble domain, TNFR2/R7 soluble domain) was analysed in colon
      cancer at the II and III stage of disease, by estimation of mRNA expression. The
      study included 80 patients with histopathologically confirmed adenocarcinoma. The
      number of TNFalpha mRNA, TNFR2 mRNA and TNFR2/R7 mRNA copies were estimated in
      tumour and healthy tissue. The highest number of mRNA TNF-alpha copies were
      investigated in all samples of tissue and independently of the stage of disease.
      Simultaneously, we noticed the largest number of mRNA copies for TNFalpha and TNF
      R2/R7 in healthy cells at stage III of the disease. It is possible to draw a
      hypothetical line separating the anti-cancer activity of TNFalpha and its
      influence on cancer progression.

PMID- 18088550
TI  - Rantes potentiates human macrophage aggregation and activation responses to
      calcium ionophore (A23187) and activates arachidonic acid pathways.
AB  - Regulated on activation, normal T-cell expressed and presumably secreted
      (RANTES), which generally mediates monocyte-macrophage (MO) activation and
      recruitment, is a protein of 8-10 kD that chemoattracts eosinophils, monocytes
      and certain T leukocyte subsets. RANTES is coded for by a gene cluster located on
      human chromosome 17 and is a human T-cell specific molecule. RANTES is a member
      of a beta intercrine subfamily reported to be a selective chemoattractant for
      human monocytes rather than neutrophils, and is also a chemoattractant for memory
      T lymphocytes, CD4+ cells. RANTES is a modulator of many important macrophage
      functions in addition to aggregation, such as chemotaxis and phagocytosis. Our
      investigations focussed on the ability to modulate the aggregation of macrophages
      induced by calcium ionophore A23187. The ionophore A23187 directly induced potent
      aggregation of MO which was markedly enhanced when the cells were pretreated with
      RANTES. However, the addition of RANTES in the absence of other co-stimuli did
      not directly induce aggregation. Additional cytokines examined for possible
      induction of macrophage aggregation were interleukin-1 (IL-1), tumor necrosis
      alpha (TNF-alpha), and IL-6; all proved to be incapable of inducing aggregation
      directly, nor did they enhance the effects of A23187 on macrophage aggregation.
      Additionally, we found that RANTES can directly stimulate MO to activate specific
      pathways of arachidonic acid cascade, inducing a synthesis and release of
      thromboxane (TxA2) and leukotriene B4 (LTB4). RANTES did not augment the potent
      ability of A23187 to induce increased production of LTB4 or TxA2 by human MO.
      These data suggest that RANTES can contribute directly to monocyte-leukocyte
      activation during inflammatory responses, resulting in greater cell aggregation,
      activation, and specific pro-inflammatory arachidonic acid products release, such
      as TxA2 and LTB4.

PMID- 18088551
TI  - T cell selection and differentiation in AIDS disease: the model of HIV-discordant
      monozygotic twins.
AB  - The model of monozygotic twins has been repeatedly studied to control the genetic
      and age-specific effects on HIV disease. Focusing on this natural model, the
      expression of CD27/CD45RA differentiation markers and the distribution of the
      Vbeta TCR repertoire was analyzed on CD4+ and CD8+ T cells. In our HIV-discordant
      monozygotic twins, a significant reduction of naive T cells and a parallel
      accumulation of effector/memory T cells was induced by HIV infection, as well as
      a skewing of T cell repertoire evidenced by VbetaTCR analysis. The block of HIV
      replication by highly active antiretroviral therapy (HAART) restored most of the
      T cell maturation and selection process, with some exception among CTL
      differentiation and repertoire. Altogether, the model of HIV-discordant
      monozygotic twins is a valuable tool showing that HAART is not able to completely
      restore the CTL profile.

PMID- 18088552
TI  - Cancer chemotherapy-induced lymphocytosis: a revolutionary discovery in the
      medical oncology.
AB  - The recent advances in the investigation of tumor immunobiology have suggested
      that cancer chemotherapy, in addition to its well known cytotoxic activity, may
      play modulatory effects on the endogenous production of cytokines involved in the
      control of both tumor angiogenesis and antitumor immunity. Cancer chemotherapy
      constantly acts with inhibitory effects on anti-bacterial, anti-viral and anti-
      mycotic immune responses, whereas its action on anticancer immunity, which is
      mainly mediated by lymphocytes, has still to be better investigated and defined.
      The present study was carried out to evaluate the influence of chemotherapy on
      lymphocyte count and its relation to the clinical response in cancer patients
      suffering from the most commonly frequent tumor histotypes, including lung,
      colorectal, breast and prostate carcinomas. The study included 144 consecutive
      metastatic solid tumor patients. Lung cancer patients were treated with cisplatin
      plus gemcitabine, colorectal cancer patients received oxaliplatin plus 5
      fluorouracil, while those affected by breast cancer or prostate carcinoma were
      treated with taxotere alone. An objective tumor regression was achieved in 66 out
      of 144 (46 percent) patients, whereas the remaining 78 patients had only a stable
      disease (SD)or a progressive disease. Independently of tumor histotype and
      chemotherapeutic regimen, a lymphocytosis occurred in patients who achieved an
      objective tumor regression in response to chemotherapy, and lymphocyte mean count
      observed at the end of the chemotherapeutic treatment was significantly higher
      with respect to the values seen before the onset of treatment. On the contrary,
      lymphocyte mean number decreased on chemotherapy in patients with SD or PD, even
      though the decline was statistically significant with respect to the pretreatment
      values in the only patients who had a PD in response to chemotherapy. This study
      would suggest that chemotherapy itself may paradoxically act, at least in part,
      as a cancer immunotherapy by inducing lymphocytosis, as well as previously
      demonstrated for the only immunotherapy with IL-2, probably by modulating the
      cytokine network and correcting the altered endogenous production of cytokines,
      responsible for cancer-related immunodeficiency.

PMID- 18088553
TI  - Immunophenotypic peculiarities of mobilized stem (CD34+) cells in blood from
      patients with severe spinal cord injury.
AB  - Immunophenotype of mobilized stem blood cells (CD34+) was studied in 29 patients
      with late post-traumatic spinal lesions. The CD34+ cells demonstrated different
      levels of expression of CD45, CD38, monomorphic determinants HLA-DR and gp130
      epitopes. Most patients presented with a CD34+ cell fraction with no or low
      expression of common leukocytic antigen CD45. Only 2 patients had greater than 15
      percent of HLA-DR-CD38- cells in the CD34+ fraction. A common transducer molecule
      of interleukin-6 family cytokines gp130 was expressed on stem (CD34+) cells in
      all the cases, 26 percent of the patients had an activated gp130 phenotype, i.e.
      a combination of C7+ and A1- epitopes.

PMID- 18088554
TI  - Interleukin -1beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor
      (TNF) in plasma and pleural fluid of pneumonia, lung cancer and tuberculous
      pleuritis.
AB  - Interleukins IL-1beta, IL-6 and TNF are increased in plasma of patients with
      severe infections and septic shock. Our objective was the evaluation of IL-1beta,
      IL-6 and TNF in plasma and exudates of pleural fluid and their contribution to
      the diagnosis. We studied 44 patients, 27 men and 17 women with mean age 66.81 +/
      11.75 years; 16 with pneumonia and parapneumonic effusion, 14 with primary lung
      cancer and pleural effusion and 14 with tuberculous pleuritis. We measured IL
      1beta, IL-6 and TNF in serum and pleural fluid with ELISA. In patients with
      pneumonia and parapneumonic effusion the mean value of IL-1beta IL-6 and TNF in
      plasma was 9.05, 19.24 and 21.34 pg/ml and in pleural fluid 10.34, 32.19 and
      25.30 pg/ml. In patients with lung cancer the mean values of IL-1beta, IL-6 and
      TNF were 5.33, 11.74 and 11.51 pg/ml and 6.70, 13.13, 20.89 pg/ml, respectively.
      In those with tuberculous pleuritis the respective mean values were 10.33, 49.94,
      21.27 pg/ml and 14, 56.59, 23.58 pg/ml. In conclusion, IL-1beta and IL-6 were
      found increased in plasma and tuberculous pleural fluid, indicating an
      inflammatory status.

PMID- 18088555
TI  - Anomalous systemic arterial supply to the left lung base without sequestration.
AB  - Systemic arterial supply from the descending thoracic aorta to the basal segment
      of the left lower lobe without a pulmonary arterial supply is a rare congenital
      anomaly within the spectrum of the sequestration lung disease. We report a case
      of a young man with anomalous systemic arterial supply to a normal left lower
      lobe referred to our department because of recurrent haemoptysis who underwent a
      successful left lower lobectomy.

PMID- 18088557
TI  - Modulation of mechanical and thermal nociceptive sensitivity in the laboratory
      mouse by behavioral state.
AB  - Experienced basic (rodent) pain researchers appreciate the influence of subject
      behavior during nociceptive testing, but such factors are not commonly reported
      and have not been systematically studied. We examined here the modulatory effect
      of behavioral state (grooming, alert, resting, light sleep, deep sleep) on
      thermal and mechanical sensitivity on the radiant heat paw-withdrawal and von
      Frey tests, respectively, in 3 mouse strains (CD-1, C57BL/6, and 129P3) with or
      without neuropathic injury. We find that in all 3 strains, grooming mice are
      relatively hypoalgesic, and robustly so in the von Frey test such that even the
      largest usable fibers are met with indifference. This grooming-related
      "hypoalgesia" persists after spared nerve injury. This finding is problematic for
      algesiometric testing in the mouse due to the considerable time mice spend
      grooming (especially on a glass floor), and ethograms of mouse behavior within
      plexiglas testing cubicles are provided as evidence of this. Alone among the 3
      strains tested, C57BL/6 mice also display robust relative hypoalgesia in deep
      sleep. Failure to consider behavioral state changes while testing may needlessly
      increase variability within and between experiments and lead to inaccurate
      conclusions in transgenic knockout studies of pain. PERSPECTIVE: State of arousal
      and attention are important modulators of pain sensitivity in humans. In this
      report, we find evidence that these same factors influence nociceptive
      sensitivity in the laboratory mouse, providing a model for understanding the
      mechanistic underpinnings of these forms of modulation.

PMID- 18088556
TI  - Sex differences in muscle pain: self-care behaviors and effects on daily
      activities.
AB  - Women have a higher prevalence of fibromyalgia and myofascial pain than men, but
      sex differences in muscle pain are inconsistently detected. We examined sex
      differences in ratings and effects of recalled and experimentally-induced muscle
      pain. In study 1 (n = 188), participants completed a questionnaire about recalled
      muscle pain. In study 2 (n = 55), participants described muscle pain from an
      exercise stimulus across 3 days by telephone. Muscle pain ratings, self-care
      behaviors for muscle pain, and effects of muscle pain on activities were
      measured. No significant sex differences were found except that women tended to
      view exercise as more effective for decreasing muscle pain than men (F (1, 187) =
      5.43, P = .02, eta(2) = .03), fewer women performed exercise for induced muscle
      pain than men, and women's activity interference was significantly higher than
      men's at the third day after exercise (F (2, 42) = 6.54, P = .01, eta(2) = .14).
      These findings support the absence of meaningful sex differences in muscle pain
      ratings. However, additional investigations are needed that consider the daily
      activities completed by people and the prevalence and incidence of performing a
      wide range of self-care behaviors for pain. PERSPECTIVE: These studies support
      that sex differences are not present in recalled and experimentally-induced
      muscle pain ratings. Therefore, we must be cautious about generalizing the
      musculoskeletal pain literature to muscle pain. Additional research is needed to
      interpret potential sex differences in self-care behaviors for muscle pain and
      activity interference from muscle pain.

PMID- 18088558
TI  - The severity of chronic pediatric pain: an epidemiological study.
AB  - This study was designed to (1) provide information on the prevalence of pediatric
      pain as well as other pain related characteristics in a sample of schoolchildren,
      and (2) study the suitability of a system to grade the severity of chronic pain
      problems among children. Participants in this cross-sectional study included 561
      schoolchildren between the ages of 8 and 16 years. Besides collecting information
      about the presence of pain at the time of interview, and in the preceding 3
      months, several characteristics of participants' pain experiences and several
      indicators of participants' quality of life were requested. Results showed that
      37.3% had chronic pain, but only 5.1% had moderate or severe chronic pain
      problems. Gender and age differences were found in the prevalence of pain
      conditions. Children who had a chronic pain condition reported a worse quality of
      life, missed more days from school, and were more likely to use pain medication
      and seek medical care for pain relief. Our study shows that chronic pain is a
      highly prevalent condition in the community, one that can exert negative
      consequence for the child. But the prevalence of severe chronic pain cases is
      low. New studies are needed to further empirically test the proposed method of
      grading the severity of chronic pain in children. PERSPECTIVE: This article
      provides information on pain problems among schoolchildren. It also suggests a
      new grading system of chronic pediatric problems. This new system could help
      clinicians and researchers to diagnose pain problems in youth and design
      treatments suited to patients' characteristics and needs.

PMID- 18088559
TI  - Morphine and ABT-594 (a nicotinic acetylcholine agonist) exert centrally mediated
      antinociception in the rat cyclophosphamide cystitis model of visceral pain.
AB  - A visceral pain model incorporating use of cyclophosphamide (CP) to induce
      bladder inflammation has been described. CP treatment in rats produces changes in
      behavior (abnormal postures and eye closure) and respiration rate indicative of
      visceral pain. We characterized the dose-dependency and progression of CP-induced
      cystitis pain after intraperitoneal (i.p.) CP. The behavioral and respiration
      rate changes were ameliorated by systemic morphine and ABT-594 [(R)-5-(2
      azetidinylmethoxy)-2-chloropyridine], a neuronal nicotinic acetylcholine receptor
      agonist, in a manner reversible by naloxone and mecamylamine, respectively. Sites
      of antinociceptive actions of morphine and ABT-594 were investigated using
      systemic, intrathecal (i.t.), or intracerebroventricular (i.c.v.) administration
      of blood-brain barrier impenetrant antagonists. Naloxone methiodide produced a
      complete antagonism of morphine antinociception after i.c.v. but not i.p. or i.t.
      administration. Chlorisondamine blocked ABT-594 antinociception after i.c.v. but
      not i.p. administration. Further pharmacological characterization of behavioral
      and respiration changes in CP-cystitis was performed using standard analgesics.
      The alpha(2)-adrenoceptor agonist clonidine produced a weak attenuation of CP
      pain behavior. NSAIDs (ibuprofen, acetaminophen, and celecoxib) and
      anticonvulsants (gabapentin and lamotrigine) were without effect. These results
      demonstrate that morphine and ABT-594 produce antinociception in CP-cystitis by a
      predominantly supraspinal site of action, and that mechanisms producing robust
      centrally-mediated antinociception could be beneficial in cystitis pain.
      PERSPECTIVE: In this article, potential antinociceptive effects of a variety of
      pharmacological agents were evaluated in a rat cystitis pain model. Morphine and
      a nicotinic acetylcholine receptor agonist ABT-594 were found to exert potent
      antinociception in this model. Findings presented here aid identification of
      agents to treat cystitis pain in the clinic.

PMID- 18088560
TI  - Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on
      opioid therapy.
AB  - We assessed the efficacy of dronabinol (Marinol capsules; Solvay Pharmaceuticals,
      Brussels, Belgium), a synthetic Delta(9)-THC (tetrahydrocannabinol), in 30
      patients taking opioids for chronic pain to determine its potential analgesic
      effects as an adjuvant treatment. Phase I of this 2-phase study was a randomized,
      single-dose, double-blinded, placebo-controlled, crossover trial in which
      subjects were randomly administered either 10 mg or 20 mg of dronabinol or
      identical placebo capsules over the course of three, 8-hour visits. Baseline self
      report measures, hourly ratings of pain intensity, pain relief, pain
      bothersomeness, treatment satisfaction, mood, side effects, and blood serum
      levels were obtained. Phase II was an extended open-label titrated trial of
      dronabinol as add-on medication to patients on stable doses of opioids. Results
      of the Phase I study showed that patients who received dronabinol experienced
      decreased pain intensity and increased satisfaction compared with placebo. No
      differences in benefit were found between the 20 mg and 10 mg doses. In the Phase
      II trial, titrated dronabinol contributed to significant relief of pain, reduced
      pain bothersomeness, and increased satisfaction compared with baseline. The
      incidence of side effects was dose-related. Overall, the use of dronabinol was
      found to result in additional analgesia among patients taking opioids for chronic
      noncancer pain. PERSPECTIVE: This study examines the effect of adding a
      cannabinoid to the regimen of patients with chronic pain who report significant
      pain despite taking stable doses of opioids. The results of our preliminary study
      suggest that dronabinol, a synthetic THC, may have an additive effect on pain
      relief.

PMID- 18088562
TI  - Hind paw incision in the rat produces long-lasting colon hypersensitivity.
AB  - Visceral injury has been shown to alter somatic sensitivity, but little is known
      about the effect of somatic insult on the viscera. In the present study, we
      examined (1) the effect of colon inflammation on somatic sensitivity and (2) the
      affect of hind paw incision on colon sensitivity. After intracolonic
      administration of trinitrobenzene sulfonic acid (TNBS) or zymosan, visceromotor
      responses to colorectal distension were increased to post-treatment day 8.
      Mechanical withdrawal thresholds in the hind paw were decreased in TNBS- and in
      zymosan-treated rats until post-intracolonic treatment day 2. There was no change
      in hind paw heat withdrawal latency in either group. Plantar incision of the hind
      paw resulted in a decrease in both hind paw mechanical withdrawal threshold and
      heat withdrawal latency and significantly increased the visceromotor response to
      colorectal distension from postincision days 1 to 8. The colon hypersensitivity
      was of longer duration than hyperalgesia at the site of hind paw incision. These
      results support the hypothesis that somatic injury and visceral inflammation can
      alter central processing of visceral and somatic inputs, respectively.
      PERSPECTIVE: Surgical procedures are common and typically associated with
      hyperalgesia at and around the site of incision. This report establishes in a
      model of postsurgical pain and hyperalgesia that a long-lasting visceral
      hypersensitivity may also accompany postsurgical hyperalgesia.

PMID- 18088563
TI  - Cardiac sodium channel mutation in atrial fibrillation.
AB  - BACKGROUND: Mutations in the sodium channel SCN5A have been implicated in many
      cardiac disorders, including the long QT syndrome, Brugada syndrome, conduction
      system disease, and dilated cardiomyopathy with atrial arrhythmias. OBJECTIVE: In
      view of the pleiotropic effects of SCN5A mutations, the purpose of this study was
      to examine a cohort of patients with familial atrial fibrillation (AF) for
      mutations in the SCN5A gene. METHODS: Probands with AF were enrolled in the study
      between June 1, 2001 and February 10, 2004. Each patient underwent a standardized
      evaluation, which included an interview, physical examination, ECG,
      echocardiogram, and blood sample for genetic analysis. Direct sequencing of the
      coding region of SCN5A was used to screen for mutations in genomic DNA. RESULTS:
      One hundred eighty-nine patients with AF were enrolled during the study period.
      From this cohort, a subset of 57 probands with a family history of AF in at least
      one first-degree relative was studied. Forty-seven subjects were men (82%); 45
      had paroxysmal AF (79%). Echocardiography revealed ejection fraction 62% +/- 6.4
      % and left atrial dimension 40 +/- 6.9 mm. A single mutation (N1986K) was
      observed in one family but was not present in more than 600 control chromosomes.
      Expression of the N1986K mutant in Xenopus oocytes revealed a hyperpolarizing
      shift in channel steady-state inactivation. CONCLUSION: In a cohort with familial
      AF, a single SCN5A mutation causing the arrhythmia in one kindred was identified.
      These data extend the range of phenotypes observed with SCN5A mutations and
      suggest that variation in the SCN5A gene is not a major cause of familial AF.

PMID- 18088564
TI  - Estimating sample size for a randomized clinical trial of lung cancer screening.
AB  - BACKGROUND: Lung cancer screening, like other screening tests, has the potential
      to save many lives, yet its benefit has not yet been shown in randomized clinical
      trials (RCTs). RCTs of screening tests require very large sample sizes and long
      follow-up periods. Investigators planning these trials need to know how the study
      design, particularly the length of accrual, the number of incident screens, the
      length of follow-up, and the method used to interpret the screening test, affect
      sample size requirements. METHODS: In this paper a tiered approach to sample size
      estimation is presented. The first tier determines the person-years at risk; the
      second tier considers the characteristics of the study population to estimate the
      frequency of preclinical disease; the third tier uses the performance of the
      screening test, the compliance rate, and the benefits of early treatment to
      estimate the incidence of clinical disease; the disease-specific mortality rates
      are estimated in the fourth tier. RESULTS: This sample size approach was utilized
      in planning a RCT of lung cancer screening with chest X-rays and a computer aided
      detection algorithm. Sample size was determined for various features of the study
      design, as well as for different assumptions about the cure rate, the treatment
      complication rate, and the rate of potential misclassification of the primary
      endpoints. CONCLUSION: The tiered approach to sample size estimation for RCTs of
      screening tests allows investigators to assess how features of the study design
      affect sample size requirements.

PMID- 18088561
TI  - Pain and stress in a systems perspective: reciprocal neural, endocrine, and
      immune interactions.
AB  - This paper advances a psychophysiological systems view of pain in which physical
      injury, or wounding, generates a complex stress response that extends beyond the
      nervous system and contributes to the experience of pain. Through a common
      chemical language comprising neurotransmitters, peptides, endocannabinoids,
      cytokines, and hormones, an ensemble of interdependent nervous, endocrine, and
      immune processes operates in concert to cope with the injury. These processes act
      as a single agent and comprise a supersystem. Acute pain in its multiple
      dimensions, and the related symptoms that commonly occur with it, are products of
      the supersystem. Chronic pain can develop as a result of unusual stress. Social
      stressors can compound the stress resulting from a wound or act alone to
      dysregulate the supersystem. When the supersystem suffers dysregulation, health,
      function, and sense of well-being suffer. Some chronic pain conditions are the
      product of supersystem dysregulation. Individuals vary and are vulnerable to
      dysregulation and dysfunction in particular organ systems due to the unique
      interactions of genetic, epigenetic and environmental factors, as well as the
      past experiences that characterize each person. PERSPECTIVE: Acute tissue injury
      activates an ensemble of interdependent nervous, endocrine, and immune processes
      that operate in concert and comprise a supersystem. Some chronic pain conditions
      result from supersystem dysregulation. Individuals vary and are vulnerable to
      dysregulation due to the unique interactions of genetic, epigenetic, and
      environmental factors and past experiences that characterize each person. This
      perspective can potentially assist clinicians in assessing and managing chronic
      pain patients.

PMID- 18088565
TI  - The process of nutrient analysis for controlled feeding trials: a comparative
      study of two South African nutrient databases with chemical analysis.
AB  - BACKGROUND: There is an increased tendency in the field of nutrition research to
      conduct more outpatient controlled feeding trials. The formulation of accurate
      diets is essential in order to assemble valid scientific data, which will
      substantiate hypothesised relationships between a nutrient variable and an
      outcome. Research dieticians rely on the accuracy of computerised nutrient
      databases when designing the menu. OBJECTIVE: The reliability of the two
      computerised nutrient databases available in South Africa containing foods from
      different food sources were investigated, comparing them with each other and with
      the reference standard of chemical analysis. METHODS: A seven day Westernized
      menu providing an energy level of 7500 kJ/day was entered into FoodFinder3 (2002)
      and Dietary Manager (modified 2006 version) Software programmes. Food prepared
      according to this menu was chemically analysed for the macronutrient profiles
      (carbohydrate, fat and protein), fatty acid distribution (saturated fatty acids,
      mono-unsaturated fatty acids and poly-unsaturated fatty acids) and total fibre,
      insoluble and soluble fibre in order to compare data. RESULTS: The two nutrient
      databases' values did not differ significantly from each other despite using
      different food sources, however, there were differences between the chemically
      analysed values and the databases' calculated values for selected nutrients.
      There were no significant differences between the amount of total energy,
      protein, carbohydrate, poly-unsaturated fatty acids and total fibre. The total
      fat, saturated fatty acid and mono-unsaturated fatty acid content using both
      FoodFinder3 and Dietary Manager were statistically and practically significantly
      higher than the chemical analysis (p<0.05). FoodFinder3 produced significantly
      lower levels of insoluble and soluble fibre compared to the chemical analysis.
      CONCLUSION: The use of computerised nutrient databases in menu design for
      controlled feeding trials is functional and assists the research dietician with
      this challenging task. However, computer nutrient databases are not reliable
      enough to exclude the step of menu validation by chemical analysis before the
      start of the intervention.

PMID- 18088566
TI  - Bronchopulmonary C-fibers modulate the breathing pattern in surfactant-depleted
      juvenile cats.
AB  - The aim of this study was to investigate the influence of nonmyelinated C-fibers
      on the breathing pattern by cooling the vagal nerves to temperatures at which
      myelinated nerve transmission from pulmonary stretch receptors is blocked (+7
      degrees C) and further at which nonmyelinated fiber input is blocked (0 degrees
      C), in anaesthetized spontaneously breathing juvenile cats with normal (L(N)),
      surfactant-depleted (L(D)) and surfactant-treated (L(T)) lungs. In L(N), vagal
      cooling from +7 to 0 degrees C decreased respiratory frequency (f(R); -8%; p <
      0.01), and increased tidal volume (V(T); +40%; p < 0.01). In the presence of
      shallow fast breathing in L(D), f(R) decreased (+38 to +7 degrees C: -26%; p <
      0.015 and +7 to 0 degrees C: -24%; p < 0.001) and V(T) increased (+37%; p < 0.049
      and +88%; p < 0.016). In L(T), f(R) decreased (+7 to 0 degrees C: -21%; p <
      0.001), whereas V(T) remained the same at 0 degrees C (+12%; NS). These findings
      show for the first time that the activity of bronchopulmonary C-fibers have a
      prominent role in modulating the breathing pattern in juvenile cats with
      surfactant-depleted lungs.

PMID- 18088567
TI  - Ventilatory long-term facilitation in non-snoring subjects during NREM sleep.
AB  - We hypothesized that very brief episodes of hypoxia (<1 min) would evoke long
      term facilitation (LTF) in individuals free of inspiratory flow limitation (IFL).
      We studied 12 healthy participants who were self-reported non-snorers and
      confirmed the absence of IFL. We induced 15 brief episodes of hypoxia during non
      REM sleep, reducing arterial oxygen saturation to 84-85%, followed by 1 min of
      room air. Ventilatory variables and resistance were measured during the control
      period, hypoxic trials, room air controls, and for 20 min following the last
      hypoxic episode. There was a significant increase in minute ventilation (108+/
      1.3% of control, P < 0.05) and tidal volume (105+/-1.7% of control, P < 0.05) and
      a significant decrease in upper airway resistance (88+/-9.8% control, P < 0.05)
      during the recovery period. However, there were no significant changes in any
      variable during sham studies. We have shown for the first time that LTF can be
      elicited in sleeping humans free of IFL.

PMID- 18088568
TI  - Pulmonary gas exchange is reduced by the cardiovascular diving response in
      resting humans.
AB  - The diving response reduces the pulmonary O(2) uptake in exercising humans, but
      it has been debated whether this effect is present at rest. Therefore,
      respiratory and cardiovascular responses were recorded in 16 resting subjects,
      performing apnea in air and apnea with face immersion in cold water (10 degrees
      C). Duration of apneas were predetermined to be identical in both conditions
      (average: 145 s) and based on individual maximal capacity (average: 184 s).
      Compared to apnea in air, an augmented diving response was elicited by apnea with
      face immersion. The O(2) uptake from the lungs was reduced compared to the
      resting eupneic control (4.6 ml min(-1)kg(-1)), during apnea in air (3.6 ml min(
      1)kg(-1)) and even more so during apnea with face immersion (3.4 ml min(-1)kg(
      1)). We conclude that the cardiovascular adjustments of the diving response
      reduces pulmonary gas exchange in resting humans, allowing longer apneas by
      preserving the lungs' O(2) store for use by vital organs.

PMID- 18088569
TI  - Acute hypoxia does not alter inter-alveolar perfusion distribution in
      unanesthetized rats.
AB  - Effects of hypoxic vasoconstriction on inter-alveolar perfusion distribution (<
      or =1000 alveoli) have not been studied. To address this, we measured inter
      alveolar perfusion distribution in the lungs of unanesthetized rats breathing 10%
      O(2). Perfusion distributions were measured by analyzing the trapping patterns of
      4 microm diameter fluorescent latex particles infused into the pulmonary
      circulation. The trapping patterns were statistically quantified in confocal
      images of the dried lungs. Trapping patterns were measured in lung volumes that
      ranged between less than 1 and 1300 alveoli, and were expressed as the log of the
      dispersion index (logDI). A uniform (statistically random) perfusion distribution
      corresponds to a logDI value of zero. The more this value exceeds zero, the more
      the distribution is clustered (non-random). At the largest tissue volume (1300
      alveoli) logDI reached a maximum value of 0.68+/-0.42 (mean+/-s.d.) in hypoxic
      rats (n = 6), 0.50+/-0.38 in hypercapnic rats (n.s.) and 0.48+/-0.25 in air
      breathing controls (n.s.). Our results suggest that acute hypoxia did not cause
      significant changes in inter-alveolar perfusion distribution in unanesthetized,
      spontaneously breathing rats.

PMID- 18088571
TI  - Chest wall kinematics and Hoover's sign.
AB  - BACKGROUND: No attempt has been made to quantify the observed rib cage distortion
      (Hoover's sign) in terms of volume displacement. We hypothesized that Hoover's
      sign and hyperinflation are independent quantities. METHODS: Twenty obstructed
      stable patients were divided into two groups according to whether or not they
      exhibited Hoover's sign during clinical examination while breathing quietly. We
      evaluated the volumes of chest wall and its compartments: the upper rib cage, the
      lower rib cage and the abdomen, using optoelectronic plethysmography. RESULTS:
      The volumes of upper rib cage, lower rib cage and abdomen as a percentage of
      absolute volume of the chest wall were similar in patients with and without
      Hoover's sign. In contrast, the tidal volume of the chest wall, upper rib cage,
      lower rib cage, their ratio and abdomen quantified Hoover's sign, but did not
      correlate with level of hyperinflation. CONCLUSIONS: Rib cage distortion and
      hyperinflation appear to define independently the functional condition of these
      patients.

PMID- 18088570
TI  - Regional cerebral blood flow during acute hypoxia in individuals susceptible to
      acute mountain sickness.
AB  - Individuals susceptible to high altitude pulmonary edema show altered pulmonary
      vascular responses within minutes of exposure to hypoxia. We hypothesized that a
      similar acute-phase vulnerability to hypoxia may exist in the brain of
      individuals susceptible to acute mountain sickness (AMS). In established AMS and
      high altitude cerebral edema, there is a propensity for vasogenic white matter
      edema. We therefore hypothesized that increased cerebral blood flow (CBF) during
      acute hypoxia would also be disproportionately greater in white matter (WM) than
      grey matter (GM) in AMS-susceptible subjects. We quantified regional CBF using
      arterial spin labeling MRI during 30 min hypoxia (F(I)O(2) = 0.125) in two
      groups: AMS-susceptible (AMS-S, n = 6) who invariably experienced AMS at
      altitude, and AMS-resistant (AMS-R, n = 6) who never experienced AMS despite
      multiple rapid ascents to high altitude. SaO(2) during hypoxia did not differ
      between groups (AMS-S = 87+/-4%, AMS-R = 89+/-3%, p = 0.3). Steady-state whole
      brain CBF increased in hypoxia (p<0.005), but did not differ between groups
      (normoxia: AMS-S = 42.7+/-14.0 ml/(100 g min), AMS-R = 41.7+/-10.1 ml/(100 g
      min); hypoxia: AMS-S = 47.8+/-19.5 ml/(100 g min), AMS-R = 48.2+/-10.1 ml/(100 g
      min), p = 0.65), and cerebral oxygen delivery remained constant. The percent
      change in CBF did not differ between brain regions or between groups (although
      absolute CBF change was greater in GM): (GM: AMS-S = 6.1+/-7.7 ml/(100 g min)
      (10+/-11%), AMS-R = 8.3+/-5.7 ml/(100 g min) (17+/-11%), p = 0.57; WM: AMS-S =
      4.3+/-5.1 ml/(100 g min) (12+/-15%), AMS-R = 4.8+/-2.9 ml/(100 g min) (16+/-9%),
      p = 0.82). CONCLUSION: CBF increases in acute hypoxia, but is not different
      between WM and GM, irrespective of AMS susceptibility. Acute phase differences in
      regional CBF during acute hypoxia are not a primary feature of susceptibility to
      AMS.

PMID- 18088572
TI  - Development and validation of a liquid chromatographic/electrospray ionization
      mass spectrometric method for the determination of salidroside in rat plasma:
      application to the pharmacokinetics study.
AB  - A sensitive and specific liquid chromatography-electrospray ionization-mass
      spectrometry (LC-ESI-MS) method has been developed and validated for the
      identification and quantification of salidroside, a major active constituent from
      Rhodiola rosea L., in rat plasma using helicid as an internal standard. The
      method involves a simple single-step liquid-liquid extraction with n-butanol. The
      analytes were separated by isocratic gradient elution on a Shim-pack ODS (4.6
      microm, 250 mmx2.0 mm i.d.) column and analyzed in selected ion monitoring (SIM)
      mode with a negative electrospray ionization (ESI) interface using the respective
      [M+Cl]- ions, m/z 335 for salidroside, m/z 319 for internal standard. The method
      was validated over the concentration range of 5-2000 ng/mL for salidroside.
      Within- and between-batch precision (R.S.D.%) were all within 6% and accuracy
      ranged from 96 to 112%. The lower limits of quantification was 5 ng/mL. The
      extraction recovery was on average 86.6% for salidroside. The validated method
      was used to study the pharmacokinetic profile of salidroside in rat plasma after
      intravenous and oral administration of salidroside. The bioavailability of
      salidroside in rats is 32.1%.

PMID- 18088573
TI  - Determination of 3-hydroxyisovalerylcarnitine and other acylcarnitine levels
      using liquid chromatography-tandem mass spectrometry in serum and urine of a
      patient with multiple carboxylase deficiency.
AB  - Due to its increased concentration in blood, 3-hydroxyisovalerylcarnitine (C5OH
      I) is an important indicator for the diagnosis of organic acidemias in newborns.
      However, C5OH-I has not been used as a standard in tandem mass spectrometric
      (MS/MS) assays because its isolation is difficult. We developed a new synthesis
      of C5OH-I and investigated its behavior by MS/MS. A method using the multiple
      reaction monitoring (MRM) mode of MS/MS with HPLC was developed which provides
      high accuracy, precision and reproducibility. Acylcarnitine profiles in the serum
      and urine of a patient with multiple carboxylase deficiency (MCD) showed
      increased levels compared to a healthy patient.

PMID- 18088574
TI  - Chromatographic investigation on acyl migration in betacyanins and their
      decarboxylated derivatives.
AB  - Chemopreventive and antioxidant action of betalain pigments can differ in
      dependence on their stereoselective properties, therefore, it is necessary to use
      relevant methods for monitoring of their possible stereoisomers. Chromatographic
      characterisation of a group of new isomers of various 6'-O-acylated betacyanins
      and decarboxylated betacyanins which were generated at low concentration by
      intramolecular pH-dependent acyl migration was studied in aqueous solutions by
      HPLC separation with diode-array and mass spectrometric detection. Under alkaline
      conditions (pH 10.5) the rate of migration was dramatically accelerated, however,
      always favouring the 6'-O-position and it was much less prominent at lower pH
      (under 7.0). The possible products of the partial rearrangement were tentatively
      identified as the 3'-O- and 4'-O-acylated forms and their relative retention
      times were provided. In malonylated betacyanins and 17-decarboxy-betacyanins the
      4'-O-forms were characterised in RP-HPLC by higher retention than the 6'-O forms,
      whereas the 3'-O-forms were always the most polar. In contrast, the isomerisation
      of hylocerenin and 17-decarboxy-hylocerenin resulted in different chromatographic
      profiles of the migration products. In 2-decarboxy- and 2,17-bidecarboxy
      betacyanins the 3'-O- and 4'-O-acylated forms eluted always before the 6'-O
      acylated betacyanins. The investigations on acyl migration in isolated 4'-O
      malonyl-betanin confirmed the strong tendency of reverse acyl migration (4'-->6')
      and also partial 4'-->3' rearrangement which were leading to the final monoester
      regioisomeric distribution (%) close to 87:7:6 (6'-O-, 4'-O-, 3'-O-).

PMID- 18088575
TI  - Sensitive determination of pheomelanin after 5-carboxyfluorescein succinimidyl
      ester precapillary derivatization and micellar electrokinetic capillary
      chromatography with laser-induced fluorescence detection.
AB  - The suitability of micellar electrokinetic capillary chromatography (MEKC) with
      laser-induced fluorescence (LIF) detection for the determination of pheomelanin
      in biological materials has been investigated. 5-Carboxyfluorescein succinimidyl
      ester was chosen as the labeling reagent to precapillary derivatize the two
      marker aminohydroxyphenylalanine (AHP) isomers produced after reductive
      hydrolysis of pheomelanin with hydriodic acid (HI). Various parameters affecting
      derivatization and separation were systematically studied. Under optimal
      conditions, the analytes could be separated within 18 min, and the relative
      standard deviations (R.S.D.) of migration time and corrected peak areas were less
      than 5.5%. Compared with the conventional high-performance liquid chromatography
      (HPLC) method with electrochemical detection, the 100-fold improvements in
      sensitivity were achieved by applying LIF detection. As a preliminary
      application, this method has been successfully applied to the determination of
      pheomelanin in two human melanoma cell cultures, black hair, melanoma tissue and
      urine samples of human melanoma patients with the spiked recoveries in the range
      of 88-96%.

PMID- 18088576
TI  - Direct injection LC-MS/MS method for identification and quantification of
      amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine and 3,4
      methylenedioxymethamphetamine in urine drug testing.
AB  - A method based on direct injection of diluted urine for the identification and
      quantification of amphetamine, methamphetamine, 3,4-methylenedioxymetamphetamine
      and 3,4-methylenedioxyamphetamine in human urine by electrospray ionisation
      liquid chromatography-tandem mass spectrometry was validated for use as a
      confirmation procedure in urine drug testing. Two deuterium labelled analogues,
      amphetamine-D5 and 3,4-methylenedioxymetamphetamine-D5, were used as internal
      standards. Twenty microliter aliquots of urine were mixed with 80 microL internal
      standard solution in autosampler vials and 10 microL was injected. The
      chromatographic system consisted of a 2.0 mmx100 mm C18 column and the gradient
      elution buffers used acetonitrile and 25 mmol/L formic acid. Two product ions
      produced from the protonated molecules were monitored in the selected reaction
      monitoring mode. The intra- and inter-assay variability (coefficient of
      variation) was between 5 and 16% for all analytes at 200 and 6000 ng/mL levels.
      Ion suppression occurred early after injection but did not affect the
      identification and quantification of the analytes in authentic urine samples. The
      method was further validated by comparison with a reference gas chromatographic
      mass spectrometric method using 479 authentic urine samples. The two methods
      agreed almost completely (99.8%) regarding identified analytes when applying a
      150 ng/mL reporting limit. Four deviating results were observed for 3,4
      methylenedioxymethamphetamine and this was due to uncertainty in quantification
      around the reporting limit. For the quantitative results the slope of the
      regression lines were between 0.9769 and 1.0146, with correlation
      coefficients>0.9339. We conclude that the presented liquid chromatographic-tandem
      mass spectrometric method is robust and reliable, and suitable for use as a
      confirmation method in urine drug testing for amphetamines.

PMID- 18088577
TI  - Effect of mesalamine on healing in experimental colon anastomosis: a randomised
      experimental study.
AB  - OBJECTIVE: We aimed to investigate the effect of mesalamine on healing of
      experimental colon anastomosis model. MATERIAL/METHODS: Forty adult male Wistar
      albino rats were performed segmentary colonic resection and end-to-end
      anastomosis. Animals were randomly divided into four groups: group I, anastomosis
      group, received no treatment (GI, n=8); group II, anastomosis+oral mesalamine
      group (100mg/kg/day); group III, anastomosis+rectal mesalamine (2mL) group,
      (GIII, n=8); group IV, anastomosis+oral mesalamine+rectal mesalamine (GIV, n=8)
      group. A sham group (n=8) was constituted and was performed laparotomy. Bursting
      pressure, hydroxyproline levels and histopathological characteristics of the
      anastomosis were analyzed. RESULTS: Although it was not statistically
      significant, there was an increase in the burst pressure of the mesalamine group.
      When hydroxyproline measurements were compared there were statistically
      significant difference between the non-treated colon and all groups. There were
      significant differences between GI and GIII-GIV, GII and GIV. The differences
      between group I and II and group II and III were not statistically significant.
      When we compared the median amount of the histopathological changes, we found
      significant difference between the anastomosis and the mesalamine groups
      (P<0.05). But when mesalamine groups were compared with each other we did not
      observe a significant difference. CONCLUSION: Mesalamine had positive effects
      which were not statistically significant on bursting pressure and statistically
      different significant effects on hydroxyproline (HP) levels based on the way of
      administration and statistically significant positive effects on histopathologic
      anastomotic healing in experimental anastomosis model.

PMID- 18088578
TI  - [Treatment of secondary hyperparathyroidism in dialysis: Report of a case-study
      of treatment failure].
AB  - In this case report, we describe the story of a 42-year-old woman on
      haemodialysis who presented a severe secondary hyperparathyroidism and
      hyperphosphataemia, despite a heavy drug treatment including 90mg cinacalcet,
      3600mg calcium carbonate and 2700mg aluminium hydroxide per day. Confronted to an
      apparent resistance to the calcimimetic, the question was: is this a true drug
      resistance or a pseudoresistance with, as clinical consequence, either a further
      increase of the dose of cinacalcet or a parathyroidectomy. To answer this
      question, we have monitored for two months drug adherence to phosphate binders
      and cinacalcet using electronic pillboxes called Medication Event Monitoring
      System (MEMS) without modifying the drug prescription. Drug adherence monitoring
      has been associated with a rapid normalisation of all laboratory parameters
      suggesting that the inefficacy of the treatment was essentially due to a
      nonadherence rather than due to a true drug resistance. This observation reminds
      us that nonadherence is one of the most frequent causes of apparent drug
      resistance, which should be considered in all cases of nonresponse to therapy.
      This case also illustrates the usefulness of electronic monitoring to identify
      problems of drug adherence and hence to improve and sustain medication intake in
      patients, including those on dialysis.

PMID- 18088580
TI  - Williams syndrome.

PMID- 18088579
TI  - CREB-1 and AP-1 transcription factors JunD and Fra-2 regulate bone sialoprotein
      gene expression in human breast cancer cells.
AB  - Bone sialoprotein (BSP) expression is detected in a variety of human osteotropic
      cancers. High expression of BSP in breast and prostate primary carcinomas is
      associated with progression and bone metastases development. In this study, we
      examined the transcriptional regulation of BSP gene expression in MDA-MB-231 and
      MCF-7 human breast cancer cells compared with Saos-2 human osteoblast-like cells.
      BSP human promoter deletion analyses delineated a -56/-84 region, which comprises
      a cAMP response element (CRE) that was sufficient for maximal promoter activity
      in breast cancer cell lines. We found that the basic fibroblast growth factor
      response element (FRE) also located in the proximal promoter was a crucial
      regulator of human BSP promoter activity in Saos-2 but not in breast cancer
      cells. Promoter activity experiments in combination with DNA mobility shift
      assays demonstrated that BSP promoter activity is under the control of the CRE
      element, through CREB-1, JunD and Fra-2 binding, in MDA-MB-231, MCF-7 and in Saos
      2 cells. Forskolin, a protein kinase A pathway activator, failed to enhance BSP
      transcriptional activity suggesting that CRE site behaves as a constitutive
      rather than an inducible element in these cell lines. Over-expression of JunD and
      Fra-2 increased BSP promoter activity and upregulated endogenous BSP protein
      expression in MCF-7 and Saos-2 cells while siRNA-mediated inhibition of both
      factors expression significantly reduced BSP protein level in MDA-MB-231.
      Collectively, these data provide with new transcriptional mechanisms, implicating
      CREB and AP-1 factors, that control BSP gene expression in breast cancer cells.

PMID- 18088581
TI  - Sciagra.

PMID- 18088582
TI  - EGF receptor signaling - a quantitative view.

PMID- 18088583
TI  - Impaired parietal magnitude processing in developmental dyscalculia.
AB  - Developmental dyscalculia (DD) is a specific learning disability affecting the
      acquisition of school-level mathematical abilities in the context of otherwise
      normal academic achievement, with prevalence estimates in the order of 3-6%.
      Behavioural studies show deficits in elementary numerical processing among
      individuals with pure DD, indicating that deficits in higher-level mathematical
      skills may stem from impaired representation and processing of basic numerical
      magnitude. Adult neuropsychological and neuroimaging research points to the
      intraparietal sulcus as a key region for the representation and processing of
      numerical magnitude. This raises the possibility of a parietal dysfunction as a
      root cause of DD. We show that, in children with pure DD, the right intraparietal
      sulcus is not modulated in response to numerical processing demands to the same
      degree as in typically developing children. This finding provides the first
      direct evidence for a specific impairment of parietal magnitude systems in DD
      during non-symbolic numerosity processing.

PMID- 18088584
TI  - Selective signalling by cuttlefish to predators.
AB  - Rather than simply escaping, prey animals often attempt to deter an attack by
      signalling to an approaching predator, but this is a risky strategy if it allows
      time for the predator to draw closer (especially when the signal is a bluff).
      Because prey are vulnerable to multiple predators, the hunting techniques of
      which vary widely, it could well be beneficial for a prey animal to discriminate
      predators and to signal only to those that are likely to be deterred. Higher
      vertebrates make alarm calls that can identify the type of predator to the
      signaller's conspecifics, and a recent study shows that squirrels direct an
      infrared deterrent signal specifically at infrared-sensitive pit-vipers and not
      at other snakes. We show here that naive juvenile cuttlefish (Sepia officinalis
      L.) use a visual signal selectively during encounters with different predatory
      species. We analysed sequences of defensive behaviours produced by cuttlefish, to
      control for effects of relative threat level (or 'response urgency'). This showed
      that a high contrast 'eyespot' signal, known as the deimatic display, was used
      before flight against visually oriented teleost fish, but not crabs and dogfish,
      which are chemosensory predators.

PMID- 18088585
TI  - Facultative but persistent trans-generational immunity via the mother's eggs in
      bumblebees.
AB  - It is widely acknowledged that a mother, and the maternal environment, can have a
      profound effect on the phenotype of her offspring. For example, immunocompetent
      vertebrate mothers can pass on immune factors to their otherwise immune naive
      offspring. Recently, it has also been demonstrated in invertebrates that maternal
      contact with pathogens and immune elicitors can have a positive impact on
      offspring resistance and immune system components. Here, using a cross-fostering
      design, we show that trans-generational immune priming in a social insect,
      similar to birds, takes place through factors in the eggs, with effects
      persisting into adult worker offspring. Additionally, eggs from immune-challenged
      mothers are imbued with increased internal antibacterial activity when they are
      laid.

PMID- 18088586
TI  - Enhancer organization: transistor with a twist or something in a different vein?
AB  - A specific group of enhancers that act in the early Drosophila embryo have a
      highly conserved arrangement of transcription factor binding sites. Computational
      modeling of these enhancers suggests interesting parallels with electronic
      transistors and optical image processors.

PMID- 18088587
TI  - Neuronal development: neighbors have to be different.
AB  - The assembly of neurons into functional circuits requires a multitude of cellular
      recognition events. Recent work on the hypervariable Drosophila Dscam gene
      revealed how a vast number of cell adhesion proteins contributes to neuronal
      patterning.

PMID- 18088588
TI  - Plant division: remembering where to build the wall.
AB  - Before mitosis, a band of microtubules accurately forecasts where the next cross
      wall will be inserted but then depolymerizes. How is this division plane
      memorized until cytokinesis? The molecular memory is being uncovered.

PMID- 18088589
TI  - Visual cortex: more wiggle room for the brain.
AB  - Experiments in which one eye of a ferret is removed at birth show subtle effects
      on the development of visual cortex maps that are in agreement with those
      predicted by theory.

PMID- 18088590
TI  - Centriole assembly: the origin of nine-ness.
AB  - Recent studies of the Chlamydomonas bld10 mutant have revealed that the ninefold
      symmetry of the centriole is set by the length of the cartwheel spokes, which
      fixes the diameter, and thereby the circumference, of the centriole.

PMID- 18088591
TI  - Animal behaviour: strategic signalling by cephalopods.
AB  - Cuttlefish are masters of disguise, rapidly changing colour to blend with their
      backgrounds. A new study shows that they break camouflage to direct warning
      messages at certain predators, but only those likely to be dissuaded by visual
      signals.

PMID- 18088592
TI  - Neglect: remembering the space left behind.
AB  - Our brain continuously creates various representations of the space around us as
      a function of our on-going behaviour. A recent study on how back space is
      represented in patients suffering from spatial neglect underscores the
      distinction between motor and non-motor space.

PMID- 18088593
TI  - Social evolution: pathways to ant unicoloniality.
AB  - Unicolonial ant species live in interlinked populations known as super-colonies,
      where workers and queens move freely. New research suggests that low intra
      specific resource competition leads to an absence of inter-colony aggression.

PMID- 18088595
TI  - Transmembrane topology of the Acr3 family arsenite transporter from Bacillus
      subtilis.
AB  - The transmembrane topology of the Acr3 family arsenite transporter Acr3 from
      Bacillus subtilis was analysed experimentally using translational fusions with
      alkaline phosphatase and green fluorescent protein and in silico by topology
      modelling. Initial topology prediction resulted in two models with 9 and 10 TM
      helices respectively. 32 fusion constructs were made between truncated forms of
      acr3 and the reporter genes at 17 different sites throughout the acr3 sequence to
      discriminate between these models. Nine strong reporter protein signals provided
      information about the majority of the locations of the cytoplasmic and
      extracellular loops of Acr3 and showed that both the N- and the C-termini are
      located in the cytoplasm. Two ambiguous data points indicated the possibility of
      an alternative 8 helix topology. This possibility was investigated using another
      10 fusion variants, but no experimental support for the 8 TM topology was
      obtained. We therefore conclude that Acr3 has 10 transmembrane helices. Overall,
      the loops which connect the membrane spanning segments are short, with
      cytoplasmic loops being somewhat longer than the extracellular loops. The study
      provides the first ever experimentally derived structural information on a
      protein of the Acr3 family which constitutes one of the largest classes of
      arsenite transporters.

PMID- 18088596
TI  - The hydroxyl group of S685 in Walker A motif and the carboxyl group of D792 in
      Walker B motif of NBD1 play a crucial role for multidrug resistance protein
      folding and function.
AB  - Structural analysis of MRP1-NBD1 revealed that the Walker A S685 forms hydrogen
      bond with the Walker B D792 and interacts with magnesium and the beta-phosphate
      of the bound ATP. We have found that substitution of the D792 with leucine
      resulted in misfolding of the protein. In this report we tested whether
      substitution of the S685 with residues that prevent formation of this hydrogen
      bond would also cause misfolding. Indeed, substitution of the S685 with residues
      potentially preventing formation of this hydrogen-bond resulted in misfolding of
      the protein. In addition, some substitutions that might form hydrogen-bond with
      D792 also yielded immature protein. All these mutants are temperature-sensitive
      variants. However, these complex-glycosylated mature mutants prepared from the
      cells grown at 27 degrees C still significantly affect ATP binding and ATP
      dependent solute transport. In contrast, substitution of the S685 with threonine
      yielded complex-glycosylated mature protein that is more active than the wild
      type MRP1, indicating that the interaction between the hydroxyl group of 685
      residue and the carboxyl group of D792 plays a crucial role for the protein
      folding and the interactions of the hydroxyl group at 685 with magnesium and the
      beta-phosphate of the bound ATP play an important role for ATP-binding and ATP
      dependent solute transport.

PMID- 18088597
TI  - Antibodies induced by liposomal protein exhibit dual binding to protein and lipid
      epitopes.
AB  - Natural polyreactive antibodies can accommodate chemically unrelated epitopes,
      such as lipids and proteins, in a single antigen binding site. Because liposomes
      containing lipid A as an adjuvant can induce antibodies directed against specific
      lipids, we immunized mice with liposomes containing lipid A together with a
      protein or peptide antigen to determine whether monoclonal antibodies generated
      after immunization would be specifically directed both to the liposomal lipid
      (either cholesterol or galactosylceramide) and also to the accompanying liposomal
      protein or peptide. Monoclonal antibodies were obtained that bound, by ELISA, to
      cholesterol and to recombinant gp140 envelope protein from HIV-1, or to
      galactosylceramide and to an HIV-1 envelope peptide. Surface plasmon resonance
      studies with the former antibody showed that the liposomal cholesterol and
      liposomal gp140 each contributed to the overall binding energy of the antibody to
      liposomes containing cholesterol and protein.

PMID- 18088598
TI  - The RXRalpha C-terminus T462 is a NMR sensor for coactivator peptide binding.
AB  - The C-terminal activation function-2 (AF-2) helix plays a crucial role in
      retinoid X receptor alpha (RXRalpha)-mediated gene expression. Here, we report a
      nuclear magnetic resonance (NMR) study of the RXRalpha ligand-binding domain
      complexed with 9-cis-retinoic acid and a glucocorticoid receptor-interacting
      protein 1 peptide. The AF-2 helix and most of the C-terminal residues were
      undetectable due to a severe line-broadening effect. Due to its outstanding
      signal-to-noise ratio, the C-terminus residue, threonine 462 (T462) exhibited two
      distinct crosspeaks during peptide titration, suggesting that peptide binding was
      in a slow exchange regime on the chemical shift timescale. Consistently, the K(d)
      derived from T462 intensity decay agreed with that derived from isothermal
      titration calorimetry. Furthermore, the exchange contribution to the (15)N
      transverse relaxation rate was measurable in either T462 or the bound peptide.
      These results suggest that T462 is a sensor for coactivator binding and is a
      potential probe for AF-2 helix mobility.

PMID- 18088599
TI  - Suppression of PMA-induced tumor cell invasion by capillarisin via the inhibition
      of NF-kappaB-dependent MMP-9 expression.
AB  - Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and
      metastasis of cancer cells. In this study, we examined the inhibitory effect of
      capillarisin, a bioactive flavonoid of Artemisia capillaries, on phorbol
      myristate acetate (PMA)-induced MMP-9 expression in MCF-7 human breast carcinoma
      cells. Capillarisin significantly and selectively suppressed PMA-induced MMP-9
      expression in MCF-7 and the Matrigel invasion assay showed that capillarisin
      reduces PMA-induced invasion of MCF-7 cells. Capillarisin has been found to
      suppress PMA-induced MMP-9 expression through inhibition of the NF-kappaB
      dependent transcriptional activity of MMP-9 gene via p38 MAPK and JNK signaling
      pathways. However, capillarisin had no effect on enzymatic activity of MMP-9 and
      expression of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2, the
      major endogenous inhibitors of MMPs. These results suggest that capillarisin
      represents a potential anti-metastatic agent suppressing cancer cell invasion
      through specific inhibition of NF-kappaB-dependent MMP-9 gene expression.

PMID- 18088600
TI  - S1P(2) receptors mediate inhibition of glioma cell migration through Rho
      signaling pathways independent of PTEN.
AB  - Sphingosine 1-phosphate (S1P) induced the inhibition of glioma cell migration.
      Here, we characterized the signaling mechanisms involved in the inhibitory action
      by S1P. In human GNS-3314 glioblastoma cells, the S1P-induced inhibition of cell
      migration was associated with activation of RhoA and suppression of Rac1. The
      inhibitory action of S1P was recovered by a small interference RNA specific to
      S1P(2) receptor, a carboxyl-terminal region of Galpha12 or Galpha13, an RGS
      domain of p115RhoGEF, and a dominant-negative mutant of RhoA. The inhibitory
      action of S1P through S1P(2) receptors was also observed in both U87MG
      glioblastoma and 1321N1 astrocytoma cells, which have no protein expression of a
      phosphatase and tensin homolog deleted on chromosome 10 (PTEN). These results
      suggest that S1P(2) receptors/G(12/13)-proteins/Rho signaling pathways mediate
      S1P-induced inhibition of glioma cell migration. However, PTEN, recently
      postulated as an indispensable molecule for the inhibition of cell migration, may
      not be critical for the S1P(2) receptor-mediated action in glioma cells.

PMID- 18088601
TI  - Determination of kynurenine in serum by high-performance liquid chromatography
      with on-column fluorescence derivatization.

PMID- 18088602
TI  - Maple syrup urine disease in treated patients: biochemical and oxidative stress
      profiles.
AB  - OBJECTIVE: The objective of this study was to evaluate and correlate the
      biochemical and oxidative stress profiles in MSUD patients during the dietary
      treatment. DESIGN AND METHODS: Plasma samples from treated MSUD patients were
      used to evaluate the biochemical profile and oxidative stress parameters.
      RESULTS: It was observed that glucose, total cholesterol, albumin and creatinine
      are reduced and that aspartate aminotransferase and lactate dehydrogenase
      activities are increased in plasma from MSUD patients under treatment. Besides,
      it was verified an increase of thiobarbituric acid-reactive species (TBARS) and a
      decrease of total antioxidant reactivity (TAR). CONCLUSIONS: Our results suggest
      that oxidative stress occurs in treated MSUD patients and that dietary treatment
      and clinical conditions associated to the disease can lead to biochemical
      alterations in these patients.

PMID- 18088603
TI  - The deletion of amino acids 114-121 in the TM1 domain of mouse prion protein
      stabilizes its conformation but does not affect the overall structure.
AB  - A mutant of mouse prion protein (PrPC) carrying a deletion of residues 114-121
      (PrPDelta114-121) has previously been described to lack convertibility into the
      scrapie-associated isoform of PrP (PrPSc) and to exhibit a dominant-negative
      effect on the conversion of wild-type PrPC into PrPSc in living cells. Here we
      report the characterization of recombinantly expressed PrPDelta114-121 by Fourier
      transformation infrared spectroscopy (FTIR) and circular dichroism (CD)
      spectroscopy. The analysis of spectra revealed an increased antiparallel beta
      sheet content in the deletion mutant compared to wild-type PrPC. This additional
      short beta-sheet stabilized the fold of the mutant protein by
      DeltaDeltaG(0)'=3.4+/-0.3 kJ mol(-1) as shown by chemical unfolding experiments
      using guanidine hydrochloride. Secondary structure predictions suggest that the
      additional beta-sheet in PrPDelta114-121 is close to the antiparallel beta-sheet
      in PrPC. The high-affinity Cu2+-binding site outside the octarepeats, which is
      located close to the deletion and involves His110 as a ligand, was not affected,
      as detected by electron paramagnetic resonance (EPR) spectroscopy, suggesting
      that Cu2+ binding does not contribute to the protection of PrPDelta114-121 from
      conversion into PrPSc. We propose that the deletion of residues 114-121
      stabilizes the mutant protein. This stabilization most likely does not obstruct
      the interaction of PrPDelta114-121 with PrPSc but represents an energy barrier
      that blocks the conversion of PrPDelta114-121 into PrPSc.

PMID- 18088605
TI  - Emerging biomaterials and tissue engineering.

PMID- 18088604
TI  - Crystallographic structure and substrate-binding interactions of the molybdate
      binding protein of the phytopathogen Xanthomonas axonopodis pv. citri.
AB  - In Xanthomonas axonopodis pv. citri (Xac or X. citri), the modA gene codes for a
      periplasmic protein (ModA) that is capable of binding molybdate and tungstate as
      part of the ABC-type transporter required for the uptake of micronutrients. In
      this study, we report the crystallographic structure of the Xac ModA protein with
      bound molybdate. The Xac ModA structure is similar to orthologs with known three
      dimensional structures and consists of two nearly symmetrical domains separated
      by a hinge region where the oxyanion-binding site lies. Phylogenetic analysis of
      different ModA orthologs based on sequence alignments revealed three groups of
      molybdate-binding proteins: bacterial phytopathogens, enterobacteria and soil
      bacteria. Even though the ModA orthologs are segregated into different groups,
      the ligand-binding hydrogen bonds are mostly conserved, except for Archaeglobus
      fulgidus ModA. A detailed discussion of hydrophobic interactions in the active
      site is presented and two new residues, Ala38 and Ser151, are shown to be part of
      the ligand-binding pocket.

PMID- 18088606
TI  - Bone morphogenetic proteins: a review for cranial and maxillofacial surgery.

PMID- 18088607
TI  - Guided bone regeneration.

PMID- 18088609
TI  - Surface modifications of implants.

PMID- 18088608
TI  - In situ forming biomaterials.

PMID- 18088610
TI  - Recent advances in cosmetic materials.

PMID- 18088611
TI  - Skin and oral mucosal substitutes.

PMID- 18088612
TI  - Materials and techniques in maxillofacial prosthodontic rehabilitation.

PMID- 18088613
TI  - Wound closure materials.

PMID- 18088614
TI  - Cartilage regeneration.

PMID- 18088616
TI  - Advanced topics in dentoalveolar surgery.

PMID- 18088615
TI  - Peripheral sensory nerve regeneration with biodegradable materials and
      neurotropic factor.

PMID- 18088617
TI  - Pre-emptive and postoperative analgesia for dentoalveolar surgery.

PMID- 18088618
TI  - Predicting the success and failure of surgical endodontic treatment.

PMID- 18088620
TI  - Root end filling.

PMID- 18088619
TI  - Ultrasonic retrograde preparation.

PMID- 18088621
TI  - Periapical surgery: clinical decision making.

PMID- 18088622
TI  - Surgical exposure of impacted teeth.

PMID- 18088623
TI  - Surgical uprighting of second molars: rationale and technique.

PMID- 18088624
TI  - Suturing principles in dentoalveolar surgery.

PMID- 18088625
TI  - Antibiotic prophylaxis in dentoalveolar surgery.

PMID- 18088627
TI  - Coding for dentoalveolar surgical procedures.

PMID- 18088626
TI  - Oral connective tissue grafting: evidence-based principles for predictable
      success.

PMID- 18088628
TI  - Current medical and surgical management of sleep related breathing disorders.

PMID- 18088629
TI  - History and epidemiology of sleep-related breathing disorders.

PMID- 18088630
TI  - Pathophysiology of obstructive sleep apnea.

PMID- 18088631
TI  - Evaluation and diagnosis of sleep-disordered breathing.

PMID- 18088632
TI  - Current medical management of sleep-related breathing disorders.

PMID- 18088633
TI  - Principles of oral appliance therapy for the management of sleep disordered
      breathing.

PMID- 18088634
TI  - Lasers in the management of snoring and mild sleep apnea.

PMID- 18088635
TI  - Surgical treatment of snoring and mild obstructive sleep apnea.

PMID- 18088636
TI  - Surgical evaluation for reconstruction of the upper airway.

PMID- 18088637
TI  - Radiofrequency thermal ablation therapy for obstructive sleep apnea.

PMID- 18088638
TI  - Nasal and palatal surgery for obstructive sleep apnea syndrome.

PMID- 18088639
TI  - Soft tissue hypopharyngeal surgery for obstructive sleep apnea syndrome.

PMID- 18088640
TI  - Genioglossus muscle advancement techniques for obstructive sleep apnea.

PMID- 18088641
TI  - Surgical changes of posterior airway space in obstructive sleep apnea.

PMID- 18088642
TI  - Postoperative management of the obstructive sleep apnea patient.

PMID- 18088643
TI  - Secondary cleft surgery.

PMID- 18088644
TI  - Facial and dental relationships in individuals with cleft lip and/or palate.

PMID- 18088645
TI  - Scar revision of the cleft lip.

PMID- 18088647
TI  - Rhinoplasty in adolescent cleft patients.

PMID- 18088646
TI  - Correction of the short upper lip in the cleft patient.

PMID- 18088648
TI  - Orthodontic approach in the treatment of the cleft patient.

PMID- 18088649
TI  - Secondary grafting in the alveolar cleft patient.

PMID- 18088650
TI  - Surgical correction of midface deficiency in cleft lip and palate malformation.

PMID- 18088651
TI  - Intraoral bone transport in clefting.

PMID- 18088652
TI  - Secondary cleft surgery and speech.

PMID- 18088653
TI  - Velopharyngeal insufficiency in patients with cleft palate.

PMID- 18088654
TI  - The management of oronasal fistulas in the cleft palate patient.

PMID- 18088655
TI  - Current concepts in the management of maxillofacial infections.

PMID- 18088656
TI  - The changing microbiology of maxillofacial infections.

PMID- 18088657
TI  - Antibiotic selection in head and neck infections.

PMID- 18088658
TI  - Diagnostic imaging of maxillofacial infections.

PMID- 18088660
TI  - Diagnosis and treatment of necrotizing fasciitis in the head and neck region.

PMID- 18088659
TI  - Diagnosis and treatment of cervicofacial actinomycosis.

PMID- 18088661
TI  - Diagnosis and treatment of diffuse sclerosing osteomyelitis of the jaws.

PMID- 18088662
TI  - Diagnosis and treatment of viral infections.

PMID- 18088663
TI  - Diagnosis and treatment of oropharyngeal candidiasis.

PMID- 18088664
TI  - Management of head and neck infections in the immunocompromised patient.

PMID- 18088666
TI  - The surgical treatment of periodontal infections.

PMID- 18088665
TI  - Diagnosis and treatment of recurrent aphthous stomatitis.

PMID- 18088667
TI  - Management of peri-implantitis.

PMID- 18088668
TI  - Management of posttraumatic soft tissue infections.

PMID- 18088669
TI  - Management of infections associated with laser-assisted cosmetic skin
      resurfacing.

PMID- 18088670
TI  - The use of prophylactic antibiotics for the prevention of postoperative
      infections.

PMID- 18088671
TI  - Complications in oral and maxillofacial surgery.

PMID- 18088672
TI  - Anesthesia complications: avoidance, recognition, and management.

PMID- 18088673
TI  - Third molar surgery and associated complications.

PMID- 18088674
TI  - Complications of temporomandibular joint surgery.

PMID- 18088675
TI  - Complications in the treatment of midfacial fractures.

PMID- 18088676
TI  - Complications in the treatment of head and neck cancer.

PMID- 18088677
TI  - Complications of orthognathic surgery.

PMID- 18088678
TI  - Complications associated with the placement of dental implants.

PMID- 18088679
TI  - Complications of mandibular distraction osteogenesis.

PMID- 18088680
TI  - Complications associated with facial cosmetic surgery.

PMID- 18088681
TI  - Complications associated with cleft lip and palate repair.

PMID- 18088682
TI  - Complications of obstructive sleep apnea surgery.

PMID- 18088683
TI  - The odontogenic keratocyst.

PMID- 18088685
TI  - Etiology and pathogenesis of keratocysts.

PMID- 18088684
TI  - The history of the odontogenic keratocyst.

PMID- 18088686
TI  - Histology and ultrastructural features of the odontogenic keratocyst.

PMID- 18088687
TI  - Odontogenic keratocysts: clinical features.

PMID- 18088688
TI  - Odontogenic keratocysts: natural history and immunohistochemistry.

PMID- 18088689
TI  - Correlative MRI and CT imaging of the odontogenic keratocyst: a review of twenty
      one cases.

PMID- 18088690
TI  - Surgical management of the odontogenic keratocyst.

PMID- 18088692
TI  - Excision of the overlying, attached mucosa, in conjunction with cyst enucleation
      and treatment of the bony defect with carnoy solution.

PMID- 18088691
TI  - The use of liquid nitrogen cryotherapy in the management of the odontogenic
      keratocyst.

PMID- 18088693
TI  - Decompression and marsupialization as a treatment for the odontogenic keratocyst.

PMID- 18088694
TI  - Treatment options for the recurrent odontogenic keratocyst.

PMID- 18088695
TI  - Molecular approaches to the diagnosis of sporadic and nevoid basal cell carcinoma
      syndrome-associated odontogenic keratocysts.

PMID- 18088696
TI  - Soft tissue flaps.

PMID- 18088697
TI  - The palatal flap.
AB  - Considering the wide variety of options for the reconstruction of posttraumatic
      and postablative intraoral defects, the palatal flap holds many advantages over
      other forms of reconstruction. It has been used successfully with minimal
      morbidity for reconstruction of defects within the reach of the flap. The cases
      presented herein demonstrate the versatility of this flap, which should be part
      of the armamentarium of the reconstructive surgeon.

PMID- 18088698
TI  - Tongue flaps in maxillofacial surgery.
AB  - The tongue provides well-vascularized tissue that can be used predictably in
      maxillofacial reconstruction. Pertinent surgical anatomy and the different
      designs and clinical applications of tongue flaps are presented. Clinical cases
      are discussed.

PMID- 18088699
TI  - The nasolabial flap.
AB  - The nasolabial flap is a straightforward and time-tested reconstructive option
      suitable for a variety of facial and oral defects. The superiorly and inferiorly
      based variants are well described in the literature and offer a rapid and
      reliable alternative to time-consuming microvascular free flaps and less esthetic
      skin grafts. Despite newer and more complex alternatives, the nasolabial flap
      maintains its prominent position in the reconstructive armamentarium of the oral
      and maxillofacial surgeon.

PMID- 18088700
TI  - Flap designs for lower lip reconstruction.
AB  - Lower lip reconstruction is ideally achieved with innervated flaps that supply
      mucosa, functional muscle, and skin. These flaps should be capable of being used
      when vermilionectomy is necessary. The size and shape of the defect determine the
      optimal flap. This article illustrates the flaps used by the authors for
      particular reconstructive problems.

PMID- 18088701
TI  - The temporalis muscle flap in contemporary oral and maxillofacial surgery.
AB  - The continued use of the temporalis muscle flap in maxillofacial surgery for over
      a century serves as a testament to its versatility and reliability. The technical
      ease of its procurement and the amount and quality of tissue available make this
      flap a valuable tool in the armamentarium of the reconstructive surgeon.

PMID- 18088702
TI  - The temporoparietal galea flap.
AB  - The temporoparietal galea flap has been rediscovered as a useful tissue transfer
      technique. It is the only single-layered fascial flap that can be transposed into
      the craniofacial and head and neck region on its vascular pedicle. In the 1990s,
      it was used extensively in the surgical reconstruction of a wide variety of
      defects in the craniomaxillofacial area, ranging from scalp and auricle defects
      to nasal and maxillo-orbital repair to all types of intraoral and even mandibular
      and pharyngeal reconstructions.

PMID- 18088703
TI  - The cervicofacial flap in facial reconstruction.
AB  - The cervicofacial flap, with or without a pectoral extension, is an excellent
      source of pliable skin with perfect color match and a similar texture to the
      surrounding tissues for reconstructing large skin defects of the face.

PMID- 18088704
TI  - The plastysma myocutaneous flap.
AB  - Reconstructing extirpative defects of the oral cavity or face frequently presents
      a significant challenge to the surgeon. This article discusses two versions of
      the platysma myocutaneous flap that have proved to be reliable and versatile
      methods for reconstructing defects of the oral cavity, lower face, and ear. The
      advantages of these regional axial pattern flaps include good color match,
      appropriate thickness, minimal donor site morbidity, easy harvesting, and an
      adjacent donor site in the same operative field. A thorough understanding of the
      pertinent anatomy, particularly with respect to the location where the vascular
      supply enters the flap pedicle, is critical to the success of this flap.

PMID- 18088705
TI  - Pectoralis major myocutaneous flap.
AB  - The pectoralis major myocutaneous flap is a versatile and predictable transfer of
      soft tissue for the reconstruction of avulsive and ablative defects of the oral
      and maxillofacial region. This article reviews preoperative considerations,
      surgical anatomy, technique, and possible complications related to the
      development of this flap.

PMID- 18088707
TI  - Dental implant site preservation and development.

PMID- 18088706
TI  - Radial forearm free flap.
AB  - The unique attributes of the radial forearm flap for head and neck reconstruction
      make it a primary choice from the reconstructive ladder. As more surgeons become
      familiar and comfortable with microvascular techniques and recognize the ease of
      its harvest, the popularity of this flap will increase. The radial forearm free
      flap should not be used for every head and neck defect. Flap choice should be
      dictated by the needs of the patient and those of the site to be reconstructed.

PMID- 18088708
TI  - Alveolar ridge reconstruction with preprosthetic surgery: a precursor to site
      preservation following extraction of natural dentition.
AB  - Before dental implant therapy became a common treatment modality, oral and
      maxillofacial surgeons managed malcontent denture patients by performing
      preprosthetic surgical procedures to enhance the denture-bearing areas of the
      intraoral cavity. Surgical techniques used today to augment and enhance deficient
      ridges to receive implants follow the same biologic principles and are employed
      to achieve the same goal: an improved alveolar ridge form of both hard and soft
      tissues. The key to successful implant treatment is providing a solid bony base
      to stabilize the implant. Therefore, the main goal for the surgeon is to preserve
      the alveolar ridge and basal bone, if present.

PMID- 18088710
TI  - Augmentation of the posterior maxilla by way of sinus grafting procedures: recent
      research and clinical observations.
AB  - This article presents some of the clinical problems with bony augmentation of the
      posterior maxilla using sinus lift procedures to effect alveolar bone
      reconstruction. The antral membrane and the bone of the antral floor have
      regenerative potential commensurate with other bone of the maxilla and mandible.
      The stem cells involved in the periosteum of the sinus floor and the
      mucoperiosteum of the oral cavity covering the osteotomy opening combine to form
      a very receptive site for grafting and surgical procedures. Distraction
      osteogenesis, with and without bone inductor cytokines, will play a prominent
      part in sinus floor augmentation and in posterior maxillary alveolar bone
      grafting in the future.

PMID- 18088709
TI  - Alveolar bone preservation following tooth extraction: a perspective of clinical
      trials utilizing osseous grafting and guided bone regeneration.
AB  - Based on data from the authors' three clinical trials that focused on the role
      exerted by various regenerative materials and techniques in preserving alveolar
      ridge dimensions following tooth extraction, there is evidence to support the use
      of nonresorbable and resorbable membranes in combination with a closed-socket
      approach. There also is evidence to support a higher predictability of the
      results with resorbable membranes compared with nonresorbable membranes because
      the latter can become exposed to the oral environment during healing. A
      combination of bioactive glass and calcium sulfate using an open-socket approach
      is of marginal benefit in preserving alveolar ridge dimensions following tooth
      extraction. More research is necessary on combining osseous graft/guided bone
      regeneration using a closed-socket approach, on assessing the quality of bone
      present in the previous extraction socket following various preservation
      techniques, and on how effectively preserved/regenerated bone supports dental
      implants.

PMID- 18088711
TI  - Alveolar ridge augmentation using membranes.
AB  - Successful augmentation of compromised ridges using membranes requires correct
      diagnosis and careful case selection. The goals of the reconstruction should be
      identified before surgery. The timing and application of membranes and selecting
      the type of bone graft specific for each site are important. The technique
      requires clinical experience in flap design and mobilization, trimming, shaping
      and stabilizing the membrane, and suturing. Careful postoperative management of
      forces on the alveolar ridge from removable appliances is required.

PMID- 18088712
TI  - Treatment of the single tooth extraction site.
AB  - This article reviews the normal sequence of events following tooth extraction,
      with an emphasis on the normal loss of labial/facial bone that results in lack of
      ideal bone width and height for an ideal single tooth implant-retained
      restoration. Interceptive strategies involving immediate grafting the extraction
      site are described. The different treatments planned for single rooted and
      multirooted tooth sites are reviewed and immediate implant placement and
      restoration treatments are presented. The material presented is evidence-based on
      objective evaluation of several single tooth studies currently in followup
      stages.

PMID- 18088713
TI  - Implant site development using ridge splitting techniques.
AB  - Ridge splitting is a useful surgical technique for preparation of the edentulous
      ridge for implant placement or interpositional bone grafting. This approach is
      limited to enhancing ridge width and is more applicable to the maxilla. The
      cortical plates of the residual ridge are carefully split and expanded to
      accommodate implant insertion or bone graft materials. A significant advantage of
      this technique is that it allows simultaneous implant placement rather than
      staging the reconstruction. This article discusses indications, limitations,
      patient evaluation, surgical approaches, and complications associated with ridge
      splitting techniques.

PMID- 18088714
TI  - Alveolar ridge development with forced eruption and distraction of retained
      natural dentition.
AB  - Orthodontic forced eruption of teeth to correct vertical periodontal defects and
      aid in the development of alveolar ridge height is a well-documented concept in
      dentistry. These procedures enhance both hard (osseous) and soft (gingival)
      tissue growth before endosseous implant placement. Key factors that influence the
      effectiveness of this type of orthodontic movement are discussed. The
      effectiveness of forced eruption of a distracted segment of bone in the anterior
      maxilla is also evaluated and a new distraction device when implants are already
      present is introduced. These procedures require a proper initial diagnosis, a
      treatment plan, and a team, interdisciplinary approach to achieve optimal
      esthetic results and patient satisfaction.

PMID- 18088715
TI  - Alveolar distraction osteogenesis for implant site development.
AB  - Alveolar distraction osteogenesis can be a valuable tool for implant site
      development. Simultaneous regeneration of hard and soft tissue and an overall
      decrease in treatment time compared with other methods of site preparation can be
      an advantage. The authors advocate the concept of "prosthetically driven alveolar
      distraction." Surgical planning should begin with visualization of the final
      restoration to determine the volume and position of the soft and hard tissue
      deficiency. Surgical guides will help the surgeon determine the vector of
      distraction. Adherence to surgical principles to avoid damage to adjacent vital
      structures and maintain vascular supply to the transport segment is necessary for
      success. Bone grafting may be necessary before or after distraction to increase
      the surgical success of the procedure. Close follow-up is needed to verify the
      appropriate distraction vector and volume. Patient management and acceptance
      should be considered in distractor design and placement.

PMID- 18088716
TI  - Growth factors in implant site development.
AB  - Applications of growth factors to implant dentistry, specifically for site
      development, are currently being investigated. They hold promise for use in
      patients with vascular compromise, such as smokers, postradiation patients, and
      persons with diabetes. Delivery of these factors has been the major difficulty,
      but techniques such as tissue engineering using gene-based therapies, poly (L
      lactide) scaffolds, alloplastic bone materials, and a biomimetic approach to bone
      engineering are currently under investigation. The merge of basic science
      research and clinical application has begun, and clinical use of growth factors
      in implant site development is one example.

PMID- 18088718
TI  - Lasers in oral and maxillofacial surgery.

PMID- 18088717
TI  - Aesthetic treatment of the anterior maxilla: soft and hard tissue considerations.
AB  - Success in implant dentistry involves preimplant augmentative surgery, precision
      in implant placement, peri-implant soft tissue management, and quality of the
      prosthetic restoration, and depends on the clinician's understanding of the
      complexity of the overall treatment. The clinician must chose proper treatment
      options to reach the expected final result. Some treatments normally require only
      proper implant placement and minimal soft tissue handling at stage 2 surgery.
      Severe situations may require additional hard and soft tissue surgical procedures
      before, at the time of, or after implant placement.

PMID- 18088719
TI  - Laser physics and tissue interaction.

PMID- 18088720
TI  - Intraoral laser surgery.

PMID- 18088721
TI  - Lasers in general dentistry.

PMID- 18088722
TI  - Pre- and postlaser skin care.

PMID- 18088723
TI  - Laser dermatopathology.

PMID- 18088724
TI  - Laser cosmetic skin resurfacing: superpulsed perspective.

PMID- 18088725
TI  - Cosmetic ablative skin resurfacing.

PMID- 18088726
TI  - A brief overview of noninvasive lasers in cosmetic maxillofacial surgery.

PMID- 18088727
TI  - The treatment of vascular and pigmented lesions in oral and maxillofacial
      surgery.

PMID- 18088728
TI  - Lasers in the management of snoring and mild sleep apnea.

PMID- 18088730
TI  - Low-level laser therapy in oral and maxillofacial surgery.

PMID- 18088729
TI  - Laser applications in temporomandibular joint arthroscopic surgery.

PMID- 18088731
TI  - Complications of CO(2) laser procedures in oral and maxillofacial surgery.

PMID- 18088732
TI  - Odontogenic tumors.

PMID- 18088733
TI  - Intraosseous ameloblastoma.

PMID- 18088734
TI  - Calcifying epithelial odontogenic tumor.

PMID- 18088735
TI  - Adenomatoid odontogenic tumor.

PMID- 18088736
TI  - Squamous odontogenic tumor.

PMID- 18088737
TI  - Central odontogenic fibroma, myxoma (odontogenic myxoma, fibromyxoma), and
      central odontogenic granular cell tumor.

PMID- 18088738
TI  - Ameloblastic fibroma, ameloblastic fibro-odontoma, and odontoma.

PMID- 18088739
TI  - Miscellaneous odontogenic tumors.

PMID- 18088740
TI  - Calcifying odontogenic cyst and dentinogenic ghost cell tumor.

PMID- 18088741
TI  - Peripheral odontogenic tumors.

PMID- 18088742
TI  - Odontogenic malignancies.

PMID- 18088743
TI  - Update in craniofacial surgery.

PMID- 18088745
TI  - Difficult questions facing the craniofacial team.
AB  - Children born with growth problems that affect the cranium or face require an
      initial correct diagnosis and appropriate specialty referral. Craniofacial
      surgery is a necessary and effective specialty that involves a multifaceted
      approach to the treatment of children with abnormal growth, deficient
      development, or traumatic or postnatal damage to the cranium and face. There are
      many unanswered questions concerning the treatment of these children that require
      ethical as well as scientific reflection by all involved in their care.
      Disagreements exist among the teams regarding both the timing of surgery and the
      best operative procedure. Reported mortality rates are 1-3% and all centers
      should have their own mortality and morbidity figures available for potential
      patients. Surgical interventions for craniosynostosis-regardless of whether it is
      isolated or syndromic-should not be undertaken lightly. These are major
      operations in infants and children. A complete multi-speciality team is necessary
      for comprehensive care of the children and their families. Which aspect of
      therapy; surgical, psychological, educational, speech or motor development is
      responsible for maximizing functional outcome for these children remains unclear
      and thus all possible services should be available.

PMID- 18088746
TI  - Positional plagiocephaly: evaluation and management.
AB  - Positional plagiocephaly is a cranial vault deformation in the presence of open
      cranial vault sutures with no negative neurologic consequences. A distinct
      morphologic pattern and patent cranial sutures noted on confirmatory radiographic
      studies distinguish positional plagiocephaly from abnormal head shapes secondary
      to craniosynostosis. Management consists of conservative (nonsurgical) means,
      depending on the extent of the cranial asymmetry and any contributing etiologic
      factors. Clinicians must be well versed in the differential diagnosis of
      plagiocephaly to determine if treatment should be surgical or nonsurgical.
      Positional plagiocephaly is a nonsynostotic condition in which there is a
      deformation of the cranial vault in the presence of otherwise open, normally
      functioning sutures. The reported incidence of positional plagiocephaly has
      increased with the implementation of "Back to Sleep" guidelines for the
      prevention of sudden infant death syndrome. Pediatricians also have maintained an
      increased awareness of the importance of early referral for evaluation of
      abnormal head shape during infancy.

PMID- 18088747
TI  - Nonsyndromic craniosynostosis: diagnosis and contemporary surgical management.
AB  - Contemporary surgical management of nonsyndromic craniosynostosis requires the
      combined expertise of a pediatric craniofacial surgeon and pediatric
      neurosurgeon. The goals of surgical intervention are the release of the affected
      suture, which allows for unrestricted development of the visceral components (eg,
      brain, eyes) and three-dimensional reconstruction of the skeletal components,
      which establishes a more normal anatomic position and contour. Surgeon who care
      for infants with these cranial and orbital malformations must maintain a thorough
      understanding of the three-dimensional anatomy, characteristic dysmorphology
      associated with the different types of synostosis, and the complex interplay that
      exists between surgical intervention and ongoing skeletal growth.

PMID- 18088748
TI  - Complications related to cranial vault surgery.
AB  - Craniofacial surgery is currently firmly established as a subspecialty, and
      operations previously regarded as exceptional are considered routine. A range of
      complications still can occur, however, from minor to devastating in nature. As
      transcranial surgery is more frequently performed, craniofacial units must take
      steps to prevent such problems, recognize them early, and treat them
      expeditiously. Infection and uncontrollable bleeding are the two most feared
      complications. Craniofacial teams should maintain accurate audit data on
      morbidity and mortality and clinical outcomes to monitor complication rates. This
      article reviews the literature on craniofacial complications and makes
      recommendations for their avoidance and treatment based on the 23-year experience
      with transcranial pediatric surgery at the Royal Children's Hospital, Melbourne,
      Australia.

PMID- 18088749
TI  - Craniofacial dysostosis syndromes: stages of reconstruction.
AB  - The term "craniofacial dysostosis" is used in a general way to describe syndromal
      forms of craniosynostosis. These disorders are characterized by sutural
      involvement that not only includes the cranial vault but also extends into the
      skull base and midfacial skeletal structures. Craniofacial dysostosis syndromes
      have been described by Carpenter, Apert, Crouzon, Sathre-Chotzen, and Pfeiffer.
      Although the cranial vault and cranial base are believed to be the regions of
      primary involvement, there is also significant impact on midfacial growth and
      development. In addition to cranial vault dysmorphology, patients with these
      inherited conditions exhibit a characteristic "total midface" deficiency that is
      syndrome specific and must be addressed as part of the staged reconstructive
      approach.

PMID- 18088750
TI  - Subcranial procedures in craniofacial surgery: the Le Fort III osteotomy.
AB  - The esthetic stigmata and functional impairments associated with craniofacial
      deformities have long challenged surgeons in the management of deficiencies of
      the middle third of the face. By their very nature, craniofacial anomalies are
      repetitive patterns of deformity that affect the different functional and
      esthetic subunits of the facial hard and soft tissues. Although numerous
      procedures exist for the management of the various craniofacial malformations in
      the middle third of the facial skeleton, only the subcranial Le Fort III
      osteotomy addresses all of the functional and esthetic components of total
      midface deficiency, when considering an extracranial approach for surgical
      correction of the deformity. This article discusses craniofacial dysostosis and
      total midface deficiency and the techniques and care involved with both.

PMID- 18088751
TI  - Treacher Collins syndrome: comprehensive evaluation and treatment.
AB  - When contemplating the reconstructive options for patients with Treacher Collins
      syndrome, surgeons must recognize the complex interplay between growth of the
      craniofacial region and the possible effects of early surgery on further growth.
      Consequently, surgical procedures for the deformities in Treacher Collins
      syndrome are staged based on the dysmorphology and the growth velocity of each
      anatomic region. This article reviews the evaluation and management
      considerations for patients with Treacher Collins syndrome.

PMID- 18088752
TI  - The role of distraction osteogenesis in the management of craniofacial syndromes.
AB  - In patients with craniofacial syndromes, the skeletal discrepancy is often
      severe, and the ability to achieve the desired movement by immediate surgical
      repositioning is difficult because of restrictions of the soft-tissue envelope.
      The technique of distraction osteogenesis has provided an additional option for
      managing congenital and acquired craniofacial deformities. The use of distraction
      osteogenesis is, however, still within its infancy as a treatment modality. It is
      unlikely that the procedure will obviate the need for definitive orthognathic
      surgery at skeletal maturity in most patients with craniofacial anomalies. The
      role of distraction osteogenesis in craniofacial surgery will continue to evolve
      rapidly with increasing experience and technological advancement. Because
      distraction osteogenesis in the facial skeleton is a relatively new approach,
      analysis of the contemporary literature is imperative, and future long-term
      studies on the effects and outcome of distraction are essential.

PMID- 18088753
TI  - Dental and orthodontic management of patients with Apert and Crouzon syndromes.
AB  - Patients with Crouzon and Apert syndromes exhibit particular orofacial features
      in combination with the craniofacial skeletal discrepancy that requires
      reconstructive surgical maneuvers at various stages of development. To maximize
      positive surgical outcomes and patient satisfaction, an interdisciplinary
      approach, including pediatric dentistry and orthodontics, within a developmental
      context is needed. Routine dental care is provided in conjunction with ongoing
      surgical and orthodontic treatment during all phases of the reconstructive
      process. The goal of orthodontic treatment in the mixed dentition is to resolve
      issues related to the aberrant eruption of the permanent teeth and favorably
      influence the occlusion when early midface advancement is planned. Orthodontic
      treatment during adolescence always is needed to prepare these patients for
      orthognathic surgery, which usually involves extraction orthodontics within the
      maxillary arch. Postsurgical orthodontic management is an important component of
      the definitive occlusal correction after orthognathic surgical procedures.

PMID- 18088754
TI  - Airway considerations in craniofacial patients.
AB  - Children with syndromic craniosynostosis have an increased risk of airway
      obstruction. Addressing this issue early in their clinical course helps ensure a
      safe result. Because of their abnormal airways and a higher risk of sleep-related
      breathing disorders, regular evaluation of the airway is recommended. An
      algorithm for evaluation, including sleep study, and management of such children
      is proposed. Patients with abnormal sleep studies should undergo endoscopy
      (nasendoscopy or flexible fiberoptic bronchoscopy) to determine the site of the
      obstruction and then adenotonsillectomy when appropriate. Continuous positive
      airway pressure, nasopharyngeal airways, or surgery, including osteotomy or even
      tracheostomy, may be necessary. Regular evaluation of the airway is critical,
      because the airway status may improve or worsen with growth of the child.
      Finally, ongoing communication with the craniofacial team allows planning of
      various procedures in the individual patient with optimal management of the
      airway.

PMID- 18088755
TI  - Advances in the molecular pathogenesis of craniofacial conditions.
AB  - The impact that the understanding of fibroblast growth factor receptor (FGFR)
      biology and its relevance to the pathogenesis of the craniosynostoses has made
      cannot be underestimated. As the genetic and molecular pathology of other
      conditions become increasingly understood, there is much hope that robust and
      relevant animal models of these conditions may be generated. From these models
      and in conjunction with laboratory studies in vitro-comes a real hope of improved
      therapeutic strategies. The future lies in increased cooperation between
      clinicians working in high-volume centers and basic scientists. This article
      decribes the results of a decade of research in which the molecular pathology of
      the craniosynostoses was unravelled. The understanding of the importance of FGFR
      mutations to the genetic etiology of craniosynostosis opened up novel studies in
      developmental biology in various tissues. Such studies describe the functional
      effects of FGFR mutations. Investigations of FGFR expression in human
      craniofacial development have related functional molecular studies to human
      craniosynostosis syndromes, which provides a link between the gene mutation and
      the affected child.

PMID- 18088756
TI  - Contemporary management of pediatric craniofacial injuries.
AB  - Significant advances have been made in the past quarter century relative to the
      management of pediatric craniofacial trauma. The recognition of salient
      differences between children and adults is paramount in craniomaxillofacial
      reconstructive efforts. Proliferation of trends toward open reduction of
      craniofacial fractures, primary cranial bone grafting, when indicated, and more
      liberal use of micro- and miniplates, requires careful consideration. Success can
      be measured only after long-term follow-up over decades. Various anatomic,
      social, environmental, economic, and cooperative issues come into play in the
      contemporary management of pediatric craniofacial injuries.

PMID- 18088757
TI  - Cranial base surgery.
AB  - Surgery of the cranial base presents significant challenges for the surgeon and
      patient alike. The goal of ablative surgery-to obtain disease-free margins
      contrasts with the patient's functional and esthetic needs. This comes into sharp
      juxtaposition in cranial base surgery. The technical and technologic advances of
      the last two decades have made surgical treatment of cranial base lesions
      possible. This article reviews the pathology, anatomy, and lateral and midline
      approaches to the cranial base.

PMID- 18088759
TI  - Minimally invasive cosmetic facial surgery.

PMID- 18088760
TI  - Anatomy and functions of the muscles of facial expression.
AB  - The public yearning for cosmetic procedures is stronger now than ever before.
      More and more doctors from various specialties are performing these procedures.
      Because muscular facial activity is one of the major forces responsible for the
      formation of wrinkles, an intimate knowledge of facial muscular anatomy is
      necessary to consistently produce successful clinical outcomes. The author
      provides an intricate review of the anatomy of the muscles of facial expression
      and their relevance to cosmetic facial surgery.

PMID- 18088761
TI  - New lip and wrinkle fillers.
AB  - Cosmetic facial surgery is an integral part of the specialty of oral and
      maxillofacial surgery, and injectable facial fillers fit well into the
      armamentarium of the contemporary oral and maxillofacial surgeon. These
      procedures are generally simple to learn, provide high patient and doctor
      satisfaction, and produce few complications.

PMID- 18088762
TI  - Advanta facial implants.
AB  - Advanta facial implants represent a new method of expanded
      polytetrafluoroethylene (ePTFE) technology and appear to be different from
      previous ePTFE products. The implants appear to work well when used for lip
      augmentation. The author has 18 months' experience with this implant. Placement
      of these implants is simple and predictable. The complication rate is low and the
      implants are serviceable. The procedure is reversible without extensive damage to
      normal tissue. The Advanta facial implant appears to be a useful option in the
      armamentarium of the cosmetic oral and maxillofacial surgeon.

PMID- 18088763
TI  - Botox injections for lower facial rejuvenation.
AB  - Botox is an excellent adjunct for rejuvenation of the lower face. It should be
      considered in addition to surgery, resurfacing, skin care, and filler materials
      to improve the appearance of the lower face. Excellent control and familiarity
      with the toxin is essential before injecting these rewarding although technically
      more demanding areas of the face. In the perioral area, a few stray units in the
      wrong muscle or wrong portion of a muscle will guarantee an unhappy patient; this
      is not an area for the novice injector. When first beginning to inject the lower
      face, lower doses and more frequent touch-ups are better than larger initial
      doses and severe complications.

PMID- 18088764
TI  - Minimally invasive percutaneous collagen induction.
AB  - PCI is a simple technique and, with the right tool, can thoroughly puncture any
      skin easily and quickly. Although a single treatment may not give the smoothing
      that is seen with laser resurfacing, the epidermis remains virtually normal. When
      the result is not sufficient, treatment can be repeated. The technique can be
      used on areas that are not suitable for peeling or laser resurfacing.

PMID- 18088765
TI  - Suture suspension lifts: a review.
AB  - There has been a recent trend toward minimally invasive procedures in all facets
      of cosmetic surgery. This trend is in keeping with a general movement toward more
      effective procedures with less tissue injury and less downtime for the patient.
      This change of attitudes is an important stimulus for the development and
      popularity of suture suspension techniques. This article describes the use of
      antiptosis suture threads in the techniques of Feather Lift, stitch lift, secure
      anchoring filaments for facial elevation lift, and adjustable vector midface
      lift. The use of these techniques in various locations and their advantages and
      disadvantages are addressed.

PMID- 18088766
TI  - Facial implants: facial augmentation and volume restoration.
AB  - Facial aesthetic surgery has progressed from a tension procedure to a surgery
      that combines volume restoration with excision of excess tissue and tension
      restoration. Atrophic changes, which occur during the natural aging process, and
      congenital deficiencies of the facial skeleton are effectively addressed with
      alloplastic and autogenous facial implants. The two most common implants are the
      midface and chin implants. Indications for the use of implants in the treatment
      of a deficient or atrophic face are reviewed.

PMID- 18088767
TI  - Submentoplasty and facial liposuction.
AB  - Submentoplasty and facial liposuction are techniques used alone or in conjunction
      with a standard face-lift that can provide dramatic improvement in facial
      esthetics. Appropriate patient selection and fundamental techniques are
      described. Avoiding common mistakes and managing complications also are
      addressed.

PMID- 18088768
TI  - Autologous fat augmentation for addressing facial volume loss.
AB  - Autologous fat augmentation is in vogue again. The realization that traditional
      cosmetic surgery has often failed to achieve a truly rejuvenated look has
      refocused attention on volume replacement. Autologous fat is truly the ideal
      filler, being available in relative abundance, nonimmunogenic, a living tissue,
      and able to take on the properties of the area into which it is infiltrated. This
      article describes the author's technique that has been used on more that 200
      patients over a 4-year period.

PMID- 18088769
TI  - Minimally invasive face-lifting: S-Lift and S-Plus Lift rhytidectomies.
AB  - Limited-incision facial rejuvenation procedures are not new. A minimal-incision
      operation involving an elliptic skin excision preauricularly was described in
      1963. Responding to the desires of many patients for a limited procedure with
      limited downtime, the S-Lift was described in 1999. The "short scar" face-lift
      has gained popularity with patients and surgeons. Much like endoscopic brow
      lifting, there are clear advantages to more limited incisions in cosmetic
      procedures. The concepts of cosmetic surgery are evolving to earlier patient
      interventions with less aggressive procedures. Surgeons must recognize this trend
      and embrace less invasive, limited-incision techniques for these selected
      patients. Indeed, less may not always be more but, in many patients, it is more
      than enough.

PMID- 18088770
TI  - Legal considerations surrounding cosmetic surgery.
AB  - Oral and maxillofacial surgeons may not be able to prevent complications from
      occurring but have significant control over enhancing quality communication with
      their patients. Surgeons who take the time to focus on detailed communications
      will most often not find themselves embroiled in protracted litigation. This
      article presents practical views from the trenches on issues of past history,
      informed consent, preparation for a case, documentation, postoperative actions,
      complications, and patient refunds and releases.

PMID- 18088771
TI  - Diagnosis and management of skin cancer.

PMID- 18088772
TI  - Introduction to skin cancer.
AB  - The incidence of skin cancer has been increasing throughout the United States and
      much of the world. Although the mortality rate of nonmelanoma skin cancer is low,
      that type of skin cancer accounts for considerable morbidity, including cosmetic
      and functional impairment. Melanoma, although less common, is a life-threatening
      malignancy if not detected and treated early. Skin cancer also significantly
      contributes to the rising costs of health care in the United States. Prevention,
      early diagnosis, and treatment are critical in helping to reduce the incidence,
      morbidity, and mortality associated with skin cancer. This article provides an
      introduction to skin cancer, including the changing incidence, clinical
      presentation, and summary of treatment and prognosis.

PMID- 18088773
TI  - Biopsy techniques for skin disease and skin cancer.
AB  - It is increasingly important for clinicians to be proficient at performing skin
      biopsies because of the prevalence of skin cancers and other skin diseases in the
      population. With the appropriate knowledge and training, the three major types of
      biopsies-shave biopsy, punch biopsy, and excisional/incisional biopsy-can be
      performed. The choice of biopsy type depends on the suspected disease pathology
      and lesion location.

PMID- 18088774
TI  - Treatment options for premalignant and malignant cutaneous tumors.
AB  - Whenever possible, surgical excision of skin cancers should be the gold standard
      of treatment. There are many considerations when choosing one treatment modality
      over another. These include the lesion's location, the surgeon's experience and
      comfort level, the patient's health status and their potential compliance, access
      to available technology, and economic considerations for the patient and the
      provider. Regardless of the type of therapy, all forms of treatment share the
      following goals: complete disease cure, preservation of normal tissue,
      preservation of function, and optimal cosmesis.

PMID- 18088775
TI  - Mohs micrographic surgery for mucocutaneous malignancies.
AB  - Mohs' micrographic surgery is a surgical technique developed for removal of
      mucocutaneous malignancies. The surgeon integrates the responsibilities of
      surgery, specimen orientation and preparation, and microscopic interpretation to
      determine tumor-free margins. It has the lowest recurrence rate of all surgical
      techniques while conserving the most tumor-free skin. In selected cases it is the
      preferred method for treating carcinomas.

PMID- 18088776
TI  - Secondary procedures in maxillofacial dermatology.
AB  - Dermatologic secondary procedures involve careful preoperative planning and
      patient preparation, skillful execution of the appropriate procedure, and
      thorough postoperative wound care. Many modalities of treatment are used,
      including skin preparation through elimination of inflammatory conditions,
      resurfacing of skin, and improvement of patient health. Proper selection of
      incisional design, local or regional flaps, and grafting techniques is key to
      successful revisional surgery. Care of the revised lesion or wound through
      medications, dressings and resurfacing techniques will optimize the end result.

PMID- 18088777
TI  - Surgical management of cutaneous melanoma of the head and neck.
AB  - Surgical management of cutaneous malignant melanoma of the head and neck requires
      careful assessment of the primary lesion, use of appropriate biopsy and excision
      technique, and assessment of the regional lymphatics in all but the thinnest of
      lesions. Sustained disease-free survival can be achieved with appropriate initial
      intervention and serial follow-up. The major significant differences between
      current and past management are the advent and acceptance (or not) of sentinel
      node biopsy technique for intermediate thickness lesions without evidence of
      lymphadenopathy and an improved, validated, staging system. Early diagnosis and
      management are crucial to improving patient survival. They are best achieved
      through education of patients and clinicians.

PMID- 18088778
TI  - Surgical management of facial skin cancer.
AB  - Surgical excision is the gold standard for management of cutaneous basal cell
      carcinoma or squamous cell carcinoma. Surgical management of nonmelanotic facial
      skin cancer requires preoperative planning and an in-depth understanding of
      reconstructive techniques, including primary closure, skin grafting, and local
      tissue flaps. The decision regarding the method of treatment of nonmelanotic skin
      cancer is highly individualized and depends on patient age, cancer size,
      histologic subtype, and site. No single therapy or technique can be used in every
      situation. The goals of treatment include complete removal of the lesion with
      preservation of normal tissue, function, and cosmesis. In this article we discuss
      the principles and techniques of surgical excision and reconstruction of site
      specific facial skin cancers.

PMID- 18088779
TI  - The role of the oral and maxillofacial surgeon in wartime, emergencies, and
      terrorist attacks.

PMID- 18088780
TI  - The role of the oral and maxillofacial surgeon in wartime, emergencies, and
      terrorist attacks.

PMID- 18088781
TI  - Tissue injury and healing.
AB  - This article provides a primer on the biochemistry of wound healing for clinical
      oral and maxillofacial surgeons, recognizing that time frames, tissue growth, and
      cell types are important factors in the healing process that may influence
      treatment, whereas the specifics of molecular composition and fiber interaction
      are less critical at the tissue level. Various injury patterns, including
      different types of lacerations, blunt and penetrating trauma, blast injuries, and
      ballistic injuries, are described with an eye toward the ultimate clinical goals
      of functional and cosmetic reconstruction. As injuries of our incredibly brave
      military soldiers are studied and treated and their outcomes ultimately assessed,
      they serve as the models to help us understand changing wound patterns and
      effects in this new age of terroristic warfare.

PMID- 18088782
TI  - Ten common myths of ballistic injuries.
AB  - The science of ballistics can be confusing. Specific treatment dogmas regarding
      ballistic injuries should be examined to ensure that they are supported by
      scientific data. If determined to be unfounded, these dogmas should be
      discontinued from the teaching centers and eliminated from clinical practice.
      Tissue injury by ballistic projectiles is caused by the design and composition of
      a bullet and the velocity it is traveling when it strikes a target. Velocity or
      projectile shape alone cannot be the basis for any treatment. Each wound must be
      evaluated individually, with the determination of care decided by fact and
      clinical assessment, not rigid treatment protocols.

PMID- 18088783
TI  - Blood substitutes: hemoglobin-based oxygen carriers.
AB  - Blood product substitutes, particularly the hemoglobin-based oxygen carriers,
      represent one of the most exciting fields of research and development in modern
      medicine. The concept has been several decades in the making, and with products
      in phase III clinical trials, the use of hemoglobin-based oxygen carriers may be
      close to reality. The potential applications are limitless with interest from the
      military and civilian sectors.

PMID- 18088784
TI  - Acute management of facial burns.
AB  - Success in accurately diagnosing and providing first-contact treatment for
      patients with facial burns relies on accurate history taking, physical
      examination, and close observation. Providers must understand the early and
      delayed effects of heat on human tissue and the respiratory system. Initial
      treatment should be aimed at preventing complications and accurately identifying
      the extent of injury and rapidly administering appropriate therapy. Vigilance is
      important given the delayed nature of edema caused by burns. Rapid diagnosis and
      early intervention are key in keeping patients alive and facilitating definitive
      burn care.

PMID- 18088785
TI  - Distribution of maxillofacial injuries in terrorist attacks.
AB  - Terrorist attacks have been occurring in Israel since the early 1970s. Israeli
      oral and maxillofacial surgeons are involved in the treatment of victims, because
      facial injuries are generally present after these attacks. Facial wounds are
      caused by blocks and stone throwing, stabbings, gunshots, and suicide bombings.
      The characteristics of each type of injury and their treatment are described.

PMID- 18088786
TI  - Improvised explosive devices and the oral and maxillofacial surgeon.
AB  - Improvised explosive devices have created a new class of casualties that presents
      a unique surgical challenge for oral and maxillofacial surgeons. The injury
      pattern and severity are different from those seen in conventional trauma
      patients. Because of battlefield circumstances, patients are sometimes delayed
      significantly in their transport to a trauma center, and they frequently arrive
      at a trauma center with hypotension, hypothermia, and acidosis. Definitive care
      is delayed while the hemodynamic status and life-threatening injuries are
      stabilized. Hospital triage protocols must be well established in advance to
      prepare a timely response to the mass casualty event. Proper resource use is an
      ever-evolving challenge for hospital staff during these times.

PMID- 18088787
TI  - Radiation injuries, triage, and treatment after a nuclear terrorist attack.
AB  - The treatment of injuries from a nuclear weapon or a radioactive dispersal device
      most likely will be in a mass casualty scenario. Radiation injuries complicate
      the treatment process, with increased emphasis on early intervention. The care of
      patients must proceed in an orderly fashion. If radiation injury occurs as part
      of a mass casualty, some organized method of triage, decontamination, evacuation,
      and treatment must be implemented. Oral and maxillofacial surgeons should plan to
      become integral members of the treatment team, especially considering their wide
      scope of training. It is important for all health care providers to become
      familiar with the types of injuries that can be expected after a radiologic
      attack and the treatment modalities that can preserve life should such a
      catastrophe occur.

PMID- 18088788
TI  - Bioterrorism and biologic warfare.
AB  - Biologic agents have been used throughout history to influence battles. Recently,
      biologic agents have been used as terrorist weapons. A review of the history of
      biologic weapons and a medical overview of the Centers for Disease Control and
      Prevention Category A and B agents is provided, including history, pathogenesis,
      clinical presentation, microbiology/virology, diagnosis, treatment, and each
      agent's use or potential use as a weapon. Background information on public health
      issues surrounding bioterrorism and the role of oral and maxillofacial surgeons
      in a bioterrorist event also is provided.

PMID- 18088789
TI  - Oral and maxillofacial injuries experienced in support of Operation Iraqi Freedom
      I and II.
AB  - Penetrating, perforating, and avulsive fragmentation injuries present a unique
      surgical challenge for oral and maxillofacial surgeons in the Iraqi theater of
      operation. Maxillofacial injuries encountered in Operation Iraqi Freedom I and
      Operation Iraqi Freedom II have presented injury patterns not encountered
      previously in other large-scale armed conflicts. Current literature in the field
      of oral and maxillofacial surgery does not cover adequately the concerns that are
      inherent to care and treatment planning at an echelon III facility. This article
      addresses clinical and surgical practice guidelines that were developed by oral
      surgeons in theater and from feedback they received from higher echelons of care.

PMID- 18088790
TI  - Maxillofacial trauma treatment protocol.
AB  - The management of complex maxillofacial injuries sustained in modern warfare or
      terrorist attack has presented military surgeons with a new form of injury
      pattern previously not discussed in the medical literature. The unique wounding
      characteristics of the IED, the portability of the weapon platform, and the
      relative low cost of development make it an ideal weapon for potential terrorist
      attacks. If potential future terrorist attacks in the United States follow the
      same pattern as the incidents currently unfolding in the Middle East, civilian
      practitioners will be required to manage these wounds early for primary surgical
      intervention and late for secondary and tertiary reconstructive efforts.

PMID- 18088791
TI  - Management of the pediatric maxillofacial patient.

PMID- 18088792
TI  - Management of impacted teeth in children.
AB  - Ankylosis remains one of the major complications associated with impacted teeth
      in children. Orthodontically-assisted eruption of an ankylosed tooth may intrude
      or displace the adjacent teeth. Children who undergo orthodontically assisted
      eruption should be followed closely to ensure that movement of an impacted tooth
      is occurring. In general, the removal or assisted eruption of impacted teeth in
      children requires a thoughtful interdisciplinary evaluation between the surgeon
      and orthodontist/primary dental care provider. Factors that must be considered
      include operative feasibility, orthodontic management, future growth, and
      psychosocial considerations. The use of emerging technology, such as cone beam CT
      and skeletal anchorage, should better equip surgeons to navigate the anatomy
      three-dimensionally and provide assistance in management of difficult cases.

PMID- 18088793
TI  - Dental implants in children.
AB  - Some children and adolescents have anodontia, partial anodontia, congenitally
      missing teeth, and lost teeth as a result of trauma, and they may benefit from
      early placement of dental implants. Clinicians should have an understanding of
      the potential risks involved in placing implants in jaws that are still growing
      and developing and consider the effect that implants have on craniofacial growth.
      Implants may act as ankylotic teeth and fail to move together with the
      surrounding structures, which produces an infraocclusion that leads to
      difficulties with prosthetics. Young patients may require general anesthesia for
      the procedure and there may be limited cooperation in maintaining good oral
      hygiene.

PMID- 18088794
TI  - Soft-tissue lesions in children.
AB  - This article reviews some of the benign and malignant oral soft-tissue swellings
      that occur in children, with an emphasis on their clinical presentation,
      etiology, histopathology, and treatment. These lesions include single and
      multiple nodules, reactive lesions, and benign and malignant neoplasms. Diseases
      discussed include reactive gingival swelling, generalized gingival fibromatosis,
      melanotic neuroectodermal tumor of infancy, fibromas, vascular lesions, salivary
      gland lesions, and infantile rhabdomyomas. Also covered are lesions that may
      present in multiples, such as neuromas, multiple endocrine neoplasia type 2b,
      neurofibromatosis, and human papilloma virus-related benign epithelial lesions.
      Benign but locally aggressive and malignant neoplasms are discussed, such as
      aggressive fibromatosis, myofibromatosis, fibrosarcoma, and rhabdomyosarcoma.

PMID- 18088795
TI  - Cysts of the jaws and advances in the diagnosis and management of nevoid Basal
      cell carcinoma syndrome.
AB  - Cysts of the jaws are a relatively commonly encountered pathologic condition, and
      a full spectrum of these lesions may present in pediatric patients. Most cystic
      lesions are of odontogenic origin, as seen in adult patients, and a range of
      surgical approaches are available for their management. These approaches are
      based on the clinical and radiologic features and the behavioral and histologic
      characteristics of each cyst. Advances in imaging techniques and laboratory
      investigations, such as immunocytochemistry and genetic analysis, will continue
      to facilitate improved diagnoses, patient management, and clinical outcomes.

PMID- 18088796
TI  - Advances in diagnosis and management of fibro-osseous lesions.
AB  - Fibro-osseous lesions are benign mesenchymal skeletal tumors in which mineralized
      tissue, blood vessels, and giant cells in varying proportions replace normal
      bone. Included in this group are fibrous dysplasia, cherubism, ossifying
      fibromas, and osteoblastoma, with fibrous dysplasia being the most common entity.
      Although fibro-osseous lesions have similar histologic and radiographic features,
      they may exhibit a wide range of biologic behaviors. Because the histologic
      appearance does not predict the rate of growth or prognosis, treatment is based
      on the clinical and biologic behavior of the tumor. The purpose of this article
      is to describe advances in diagnosis and management of fibro-osseous lesions.

PMID- 18088797
TI  - Oral surgical aspects of child abuse and neglect.
AB  - Oral trauma is a frequent manifestation of child abuse. Injuries to the oral hard
      and soft tissues are common in active children, but any oral injury in a young
      preambulatory infant should raise concern for abuse. Oral-facial trauma may be
      the primary presenting injury, or may accompany other severe inflicted injuries
      such as head injury, fractures, or abdominal trauma. Some congenital or acquired
      medical disorders may be mistaken for abuse or neglect. The oral surgeon is a
      critical participant in the collaborative management of child abuse cases.

PMID- 18088798
TI  - Condyle and ramus-condyle unit fractures in growing patients: management and
      outcomes.
AB  - Controversy exists regarding the best management of ramus-condyle unit fractures.
      Treatment recommendations include observation (with or without physiotherapy or
      use of functional appliances), maxillomandibular fixation (for varying durations
      of time), and open reduction internal fixation (with varying degrees of
      maxillomandibular fixation postoperatively). Some unique complications also may
      occur after ramus-condyle unit fractures, including asymmetric mandibular growth
      and temporomandibular joint ankylosis. The purpose of this article is to review
      the evaluation and management of ramus-condyle unit fractures in growing patients
      with an emphasis on treatment outcomes.

PMID- 18088799
TI  - Pediatric mandibular hypomobility: current management and controversies.
AB  - Limited range of motion of the pediatric mandible (eg, mandibular hypomobility)
      presents many challenges. Untreated or recurrent hypomobility can cause problems
      with mastication, oral hygiene, speech, growth, and the airway. Treatments for
      ankylosis or adhesions include coronoidectomy, gap arthroplasty, costochondral
      rib reconstruction, prosthetic joint replacement, and transport distraction
      osteogenesis. There are many different causes of mandibular hypomobility in young
      patients, including idiopathic (congenital), posttraumatic, infectious,
      inflammatory, neoplastic, and iatrogenic. A detailed evaluation and diagnosis of
      the limited range of motion are critical to developing an appropriate treatment
      strategy. This article outlines evaluation, differential diagnosis, and the
      current operative approaches for treating hypomobility in young patients.
      Controversies related to timing of various procedures and the uses of various
      treatment options are discussed.

PMID- 18088800
TI  - Dealing with the effects of juvenile rheumatoid arthritis in growing children.
AB  - Juvenile rheumatoid arthritis is a chronic childhood disease that has a
      multiplicity of effects on the growth and development of the facial skeleton. An
      understanding of the disease in general and its therapy is necessary for
      successful surgical-orthodontic care.

PMID- 18088801
TI  - Mandibular distraction osteogenesis in children.
AB  - Distraction osteogenesis is currently considered a useful treatment option for
      the correction of specific facial skeletal deformities. Although it is apparent
      that distraction may have significant potential and broader application in the
      management of maxillofacial problems, very few comprehensive scientific data
      exist, making it difficult to describe its exact role in the reconstructive oral
      and maxillofacial surgeon's armamentarium. This article reviews the biological
      basis for distraction osteogenesis, potential applications, and current surgical
      approaches for mandibular distraction in children.

PMID- 18088802
TI  - Distraction osteogenesis of the midface.
AB  - Distraction osteogenesis has become an important part of pediatric oral and
      maxillofacial surgery. It is especially useful in the midface to overcome the
      perturbations of growth caused by congenital malformations, benign and malignant
      tumors, and traumatic injuries. Midfacial distraction osteogenesis can take
      various forms, depending on the exact anatomic site where it is applied in the
      midfacial skeleton. This article reviews the various locations in the midface in
      which distraction techniques might be used and highlights the important
      differences in application at these sites.

PMID- 18088803
TI  - Orthognathic surgery for secondary cleft and craniofacial deformities.
AB  - Orthognathic surgery is a critical component of surgical management of
      craniofacial deformities such as cleft lip and palate, craniofacial dysostoses,
      and mandibulofacial dysostoses. These operations can correct discrepancy in jaw
      relationship and malocclusion, relieve airway obstruction, correct facial
      asymmetry, optimize facial aesthetics, improve speech articulation, improve
      ability to masticate, and enhance psychological development and social
      interaction. Oral and maxillofacial surgeons who treat these deformities should
      be part of a craniofacial team to provide interdisciplinary care for patients.
      Distraction osteogenesis is a useful technique in the management of severe
      craniofacial deformities but does not replace conventional orthognathic surgery,
      which is safe and predictable. Recent advances in three-dimensional imaging and
      planning tools have made it possible to plan surgery more accurately and
      predictably.

PMID- 18088804
TI  - Perioperative management of the oral and maxillofacial surgery patient, part I.

PMID- 18088806
TI  - Perioperative laboratory and diagnostic testing--what is needed and when?
AB  - Preoperative patient evaluation is an essential component of any surgical
      practice. A complete history and physical, along with appropriate diagnostic
      tests, are performed routinely to ensure a safe and predictable delivery of care.
      Oral and maxillofacial surgeons use this principle in everyday practice.
      Regardless of type of surgery and practice (office-based dentoalveolar surgery,
      orthognathic surgery, trauma, elective aesthetic surgery), oral and maxillofacial
      surgeons must formulate a decision-making process and a treatment plan regarding
      the perioperative management of patients. The anesthetic plan and the surgical
      plan must be assessed preoperatively.

PMID- 18088807
TI  - Fluid and electrolyte management and blood product usage.
AB  - Traditionally, the majority of oral and maxillofacial surgery patients are young
      and healthy. With the ever-expanding scope of the specialty, however, more
      surgically extensive procedures increasingly are being performed on more
      medically complex patients. To optimize comprehensive patient care, oral and
      maxillofacial surgeons are obligated to possess a firm knowledge of the basic
      principles of fluid management and use a sound strategy for blood product usage.

PMID- 18088808
TI  - Perioperative risk assessment in the surgical care of geriatric patients.
AB  - Advances in surgical and anesthetic techniques, combined with sophisticated
      perioperative assessment, are factors that have contributed to an expanding
      number of older adults undergoing oral and maxillofacial surgery. Clinical
      competency and ability to evaluate carefully the pathophysiologic risk of
      comorbid disease become paramount in order to provide safe, expedient, and
      effective surgical care. This review article attempts to focus on the importance
      of perioperative risk assessment in geriatric surgical patients. Specifically,
      medical workup of comorbid systemic illnesses and pharmacologic therapy are
      assessed in order to determine appropriate treatment strategies for successful
      surgical outcomes.

PMID- 18088809
TI  - Perioperative considerations in the management of pediatric surgical patients.
AB  - Pediatric anatomy and physiology differ significantly from those of adults and,
      therefore, require special considerations in evaluation and perioperative
      management. This article highlights the anatomic and physiologic differences that
      influence pediatric management. It also covers specific disease processes that
      are common in the pediatric population and that may involve special management
      strategies.

PMID- 18088810
TI  - Postoperative care of oral and maxillofacial surgery patients.
AB  - The postoperative care of a surgical patient will depend on the site of the
      surgery, the nature of the surgery, the type of anesthesia used, and co
      morbidities from diseases of major organ systems. Despite these variables,
      certain general principles are applicable and are discussed in this article.
      Important aspects of the immediate postoperative phase and pain management are
      emphasized along with the concepts of general postoperative care.

PMID- 18088811
TI  - Psychologic considerations in the management of oral surgical patients.
AB  - Entering the often-sterile milieu that characterizes most surgical and
      presurgical environments sets into motion, for most patients, emotional or
      psychologic reactions. At times, these inner stirrings may manifest in the form
      of outward behaviors, such as expressions of anxiety or anger or verbalizations
      suggestive of depression. The essential psychologic issue is that undergoing any
      surgery--minor, major, elective, or urgent--is far from an emotionally neutral
      event for typical oral surgical patients.

PMID- 18088812
TI  - Fever work-up and management in postsurgical oral and maxillofacial surgery
      patients.
AB  - This article focuses on the etiology, diagnosis, and management of fever in
      postoperative oral and maxillofacial surgery patients. A list of the causes of
      postoperative fever can be exhaustive. This article focuses on the more common
      presentations relevant to oral and maxillofacial surgeons. Some rare but
      important causes also are discussed. To be comprehensive in covering this topic,
      a definition of fever and an overview of its pathophysiology are included.

PMID- 18088813
TI  - Perioperative management of patients who have pulmonary disease.
AB  - The identification of risk factors and optimization of respiratory status are
      crucial to the successful management of patients who have pulmonary disease and
      are undergoing a surgical procedure. This article explores the approach to
      pulmonary patients, from the preoperative assessment to the intraoperative and
      postoperative periods. The management of specific pulmonary disorders in the
      perioperative period is discussed.

PMID- 18088814
TI  - Prevention of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a preventable cause of significant morbidity and
      mortality in hospitalized patients, especially in the perioperative period. After
      identifying the risk factors, it is possible to stratify patients into groups
      based on their degree of risk for developing VTE. Methods available for the
      prevention of VTE vary in degree of intensity, efficacy, and side effects. The
      type of preventive measure used for each patient is based on matching the degree
      of risk for VTE with the intensity of prophylaxis, keeping in mind the risk
      benefit ratio. This article discusses VTE prophylaxis relevant to oral and
      maxillofacial surgery patients.

PMID- 18088815
TI  - Wound healing and perioperative care.
AB  - Wounding or injury unleashes a tightly choreographed array of cellular,
      physiologic, biochemical, and molecular processes that restore the integrity and
      functional capacity of damaged tissue. Healing in the orofacial region usually is
      taken for granted, yet local and systemic factors can hinder the process of
      tissue restitution and set the stage for adverse outcomes. Although surgical
      attention focuses on local wound care, consideration of systemic factors is
      equally important. An understanding of the biologic underpinnings of the wound
      healing continuum provides surgeons with a framework for developing the skills
      required to care for wounds and facilitate healing.

PMID- 18088816
TI  - Nutritional aspects of care.
AB  - Malnutrition in the oral and maxillofacial surgery surgical patient can have
      critical implications in the overall well-being and prognosis of the long-term,
      hospitalized, ill patient. The OMS should be capable of assessing the patient's
      nutritional status and nutritional requirements and developing appropriate
      recommendations for proper nutritional management. Knowledge of the various
      modalities of nutritional support should be readily available to the OMS
      practitioner.

PMID- 18088817
TI  - Perioperative management of the oral and maxillofacial surgery patient, part II.

PMID- 18088818
TI  - Perioperative pain management.
AB  - Perioperative pain management requires a multifaceted approach. The local
      inflammatory injury and the local and centrally mediated responses must be
      understood and evaluated to be treated appropriately. This article reviews the
      different classes of medication and where each one fits into a pain management
      plan. The implementation of multimodal therapy, which combines different
      techniques, routes of administration, and different drugs, must be managed. Our
      ultimate goals are to provide safe and effective pain management, reduce adverse
      outcomes, preserve patients' physical and psychological well-being, and improve
      the quality of life for patients with acute pain during the perioperative period.

PMID- 18088819
TI  - Perioperative treatment of the patient taking anticoagulation medication.
AB  - Various pharmacologic methods can be used to treat or prevent complications, such
      as deep venous thrombosis, or other sequelae related to a hypercoagulable state.
      Patients who take anticoagulation medications may be seen by oral and
      maxillofacial surgeons for evaluation and surgery in elective, urgent, and
      emergent situations. The purpose of this article is to familiarize readers with
      commonly encountered medications and recently published findings regarding their
      use by patients at risk of thromboembolic events.

PMID- 18088820
TI  - Perioperative management of the patient with hematologic disorders.
AB  - Bleeding at the time of surgery has the potential to become a serious
      complication. Careful patient assessment and review of history are of the utmost
      importance if this situation is to be avoided on the operating table.
      Unfortunately, many patients, particularly younger individuals with little to no
      previous exposure to surgery, are unaware of underlying bleeding disorders that
      they may have. Understanding the basic pathophysiology and management of these
      conditions becomes critical for the treating surgeon. For patients who have known
      conditions, close interconsultation with the treating hematologists and careful
      observation of preoperative, intraoperative, and postoperative established
      protocols reduces the risk of complications for patients and makes the
      possibility of success a reality for these individuals.

PMID- 18088821
TI  - Infection, host resistance, and antimicrobial management of the surgical patient.
AB  - Chemotherapeutic management of the microbial milieu that impacts patients
      undergoing surgery is profoundly important in surgery involving the head and neck
      region. This region is a repository for a diverse population of microbes, which
      stand ready to invade the underlying structures once the barriers have been
      breached. This article evaluates human resistance to these microorganisms and
      reviews conditions that may increase susceptibility in patients undergoing
      surgery.

PMID- 18088822
TI  - Perioperative considerations of the patient on cancer chemotherapy.
AB  - Chemotherapeutic treatment of cancer has made great progress over the past 25
      years and is frequently used as an important component of combined-modality
      therapy with surgery and radiation. Individuals undergoing cancer treatment with
      chemotherapeutic drugs frequently experience oral complications that may require
      oral surgical intervention. This article reviews the categories of drugs that are
      used and their side effects, and possible management strategies for patients
      undergoing cancer treatment with chemotherapy drugs in oral surgery practice.

PMID- 18088823
TI  - Perioperative management of the female and gravid patient.
AB  - Care of female and gravid patients requires a detailed understanding of the
      unique issues inherent to quality treatment. Increasingly important data continue
      to accumulate about significant differences in the physiology of men and women
      and the way they express disease. Furthermore, the gravid patient requires
      specific alterations and considerations in clinical care that not only affect the
      mother but also the fetus. This article focuses on key elements that the treating
      surgeon should consider.

PMID- 18088824
TI  - Perioperative management of patients with renal disease.
AB  - The patient who has renal disease is susceptible to many potential complications
      during the perioperative period. The prevention of postoperative acute renal
      failure (ARF), especially in patients who have existing chronic kidney disease,
      and management of patients who have end-stage renal disease (ESRD) who are
      undergoing surgery are challenging. Elimination of risk factors for ARF and early
      diagnosis of ARF should improve patient outcomes. For patients who have ESRD, a
      thorough and comprehensive evaluation is necessary to decrease morbidity and
      mortality associated with the end-organ damage. This article reviews the
      prevention of postoperative ARF and the perioperative management of patients who
      have ESRD who are undergoing surgery.

PMID- 18088825
TI  - Perioperative management of the patient with liver disease and management of the
      chronic alcoholic.
AB  - Each year millions of Americans undergo surgical procedures requiring local,
      general, or spinal epidural anesthesia. A disproportionate number of the patients
      are older than age 65, and up to 10% of the patients have end-stage liver
      disease. Most patients do not suffer complications as a result of the surgical
      procedure or the anesthetic. However, about 3% to 10% of patients experience
      significant morbidity, often caused by infections or cardiac or pulmonary
      complications. Patients who have serious liver disease are generally believed to
      be at increased risk for perioperative morbidity and mortality. Appropriate
      preoperative evaluation is the cornerstone of successful intra- and postoperative
      management of the effects of anesthesia and surgery and is necessary for
      combating complications that may result from preexisting liver disease.

PMID- 18088826
TI  - Perioperative management of maxillofacial tumor and reconstruction patients.
AB  - Patients who undergo maxillofacial tumor surgery and reconstruction present many
      perioperative management challenges. This patient population commonly presents
      with significant medical comorbidities in addition to the site-specific
      challenges of these tumors and the complexity of the reconstructive surgeries.
      This article combines a review of the relevant literature and the experience of a
      busy regional maxillofacial tumor and reconstruction referral center to provide a
      concise reference for management of patients. In addition to the valuable system
      specific information presented, the article outlines a daily clinical pathway,
      which is easily adapted to any clinical practice performing complex maxillofacial
      surgery.

PMID- 18088827
TI  - Gastrointestinal diseases and considerations in the perioperative management of
      oral surgical patients.
AB  - This article presents commonly encountered and clinically significant entities
      affecting the gastrointestinal (GI) system with emphasis on assisting the
      clinician in developing management strategies to reduce the associated risks.
      Xerostomia, osteoradionecrosis, gastroesophageal reflux disease, and ulcerative
      diseases occurring in the proximal portion of the GI system and antibiotic
      associated diarrhea, pseudomembranous colitis, adynamic ileus, and malabsorption
      problems occurring in the distal portion are presented. Lastly, suggestions for
      managing patients who have splenomegaly and splenectomy are addressed.

PMID- 18088828
TI  - Perioperative management of the diabetic patient.
AB  - Diabetes is a chronic disease characterized by the body's inability to process
      blood glucose properly. It is generally classified as insulin-dependent diabetes
      mellitus (IDDM), or type 1, and non-insulin-dependent diabetes mellitus (NIDDM),
      or type 2. Type 1 is characterized by a defect in insulin secretion by the beta
      cells of the pancreas, usually secondary to autoimmune destruction of those
      cells. Type 2 is characterized by peripheral insulin resistance with an insulin
      secretory defect that varies in severity. Diabetes is a common medical condition
      that affects 6% of Americans younger than 50 years and approximately 10% to 15%
      of those older than 50 years. Increasing numbers of patients who have diabetes
      are presenting to the oral surgeon's office for care. Patients who have diabetes
      have a 50% chance of undergoing a surgical procedure in their lifetime.

PMID- 18088829
TI  - Early perioperative care of the acutely injured maxillofacial patient.
AB  - The initial management of a maxillofacial trauma patient requires an intimate
      knowledge of airway management options. Deciphering clinical clues in diagnosing
      uncommon injuries require a high index of suspicion. This article addresses the
      initial airway management and presents the early management of cerebrospinal
      fluid leaks and intracranial, ocular, laryngeal, vascular, cervical spine, and
      facial bone injuries.

PMID- 18088832
TI  - History of temporomandibular joint surgery.
AB  - This article reviews past surgical treatments for TMJ and their rationale.
      Because of poor outcomes with alloplastic materials in the 1980s, many experts
      believed TMJ surgery had failed. Those who advocated nonsurgical treatment
      condemned the entire discipline without recognizing the benefits of many surgical
      approaches. Only after 20 years of "good science" has TMJ surgery reemerged with
      many procedures proven highly effective.

PMID- 18088833
TI  - Evaluation of the patient for temporomandibular joint surgery.
AB  - Temporomandibular joint (TMJ) surgery is the preferred treatment for tumors,
      neoplasms, and selected injuries and infections of the TMJ. It is also an
      appropriate and effective treatment for subsets of temporomandibular disorders
      (TMDs) that are characterized by mechanical disruption of joint function. Careful
      and systematic clinical evaluation and imaging is required to determine if
      painful TMD with altered range of motion is amenable to surgery of the TMJ. This
      article offers a rational approach to evaluation of patients for TMJ surgery.

PMID- 18088834
TI  - Nonsurgical treatment as an adjunct to surgery.
AB  - Although some temporomandibular joint problems require surgical intervention,
      nonsurgical modalities are essential in the treatment of most joint afflictions,
      including internal derangements, inflammatory conditions, and arthritides. These
      approaches are crucial for presurgical management of these conditions and are an
      important adjunct in postsurgical care.

PMID- 18088835
TI  - Arthrocentesis--incentives for using this minimally invasive approach for
      temporomandibular disorders.
AB  - TMJ arthrocentesis is a nonarthroscopic lavage performed through two needles that
      are introduced into the upper compartment of the joint. Complemented by joint
      unloading and physiotherapy, this procedure often replaces surgical intervention
      in the TMJ. The procedure is highly efficient for resolving TMJ disorders caused
      by adhering forces or friction that are eliminated by lavage, such as
      intermittent clicking, anchored disc phenomenon, and open lock, and releases
      approximately 70% of the symptomatic TMJ osteoarthritis. The outcomes are
      sufficiently effective to prevent further surgical intervention. Arthrocentesis
      is a valuable diagnostic tool and the aspirated fluid can be used efficiently for
      diagnosis, therapy, and research of TMJ disorders.

PMID- 18088836
TI  - Advanced arthroscopic surgery.
AB  - Improvements in camera and lens technology have advanced the ability to diagnose
      a multitude of pathologic conditions within the temporomandibular joint. Laser
      advances have allowed for precise surgical procedures to be performed in small
      joints with limited access. The creativity and ingenuity of oral and
      maxillofacial surgeons has taken these technologic advances and applied them to
      the treatment of this important joint.

PMID- 18088837
TI  - A biomechanical basis for primary arthroplasty of the temporomandibular joint.
AB  - Biomechanical principles of temporomandibular joint (TMJ) loading are unique,
      particularly in an orthopedic system that exhibits curvilinear general plane
      motion. Certain type-specific derangements can be surgically challenging and may
      primarily require open arthrotomy techniques rather than arthroscopy. This
      article discusses the basic biomechanical principles in normal and pathologic
      function. Three-dimensional preoperative imaging of TMJs is necessary for
      appropriate assessment of all patients and when open techniques are necessary as
      the initial surgical procedure.

PMID- 18088838
TI  - Modified mandibular condylotomy.
AB  - Modified condylotomy is a technically simple extra-articular procedure for the
      surgeon who is comfortable with intraoral vertical ramus osteotomy for
      orthognathic surgery. Increasing joint space frequently promotes disc reduction
      in joints with disc displacement with reduction or recent progression to disc
      displacement without reduction; improves pain even if disc position remains
      unchanged; and seems to favorably alter the natural course of internal
      derangement.

PMID- 18088839
TI  - Distraction osteogenesis in reconstruction of the mandible and temporomandibular
      joint.
AB  - The purpose of this article is to review the origins of temporomandibular joint
      disease that require joint reconstruction. We discuss our experience with this
      alternative procedure as an option in patients with pre-existing failed total
      joints, autoimmune degeneration, traumatic destruction, or congenital hypoplasia
      or aplasia. We also discuss the procedure as an autogenous alternative to
      prosthetic reconstruction in patients in whom reconstruction of the mandibular
      condyle and meniscus is indicated.

PMID- 18088840
TI  - Total joint reconstruction--autologous or alloplastic.
AB  - The functional goals of temporomandibular joint (TMJ) reconstruction are the same
      regardless of whether they are accomplished with autogenous tissues or
      alloplastic materials. Which of these reconstruction modalities is best suited
      for an individual case should depend on the nature of the defect, the pathology
      that created that defect, the history of the course of the patient's prior
      nonsurgical and surgical interventions and the response to each, and most
      importantly on the evidence from refereed literature that supports the choice of
      alloplast verses autogenous reconstruction based on scientific data. This article
      provides an evidence-based review of the autogenous and alloplastic TMJ
      reconstruction literature. The reader can then more accurately determine which of
      these two modalities provides the most appropriate option for the management of
      the above conditions so as to achieve the functional goals.

PMID- 18088841
TI  - Management of surgical failures.
AB  - Surgical intervention is appropriate in a small percentage of patients with
      temporomandibular joint disorders when it is based on a specific diagnosis of
      intracapsular pathology not amenable to nonsurgical modalities. Expected advances
      in our understanding of the complex molecular, biochemical, and genetic factors
      that influence these disease states clearly will allow less invasive techniques
      and even obviate the need for some open arthroplastic interventions altogether in
      the future. In the meantime, reasonable, well-intentioned surgeons must rely on
      the current body of surgical knowledge to use surgery as judiciously as possible.

PMID- 18088842
TI  - Preface.

PMID- 18088843
TI  - Oral premalignant lesions: management considerations.

PMID- 18088844
TI  - Evaluation and staging of oral cancer.

PMID- 18088846
TI  - Advances in the detection and diagnosis of oral precancerous and cancerous
      lesions.

PMID- 18088845
TI  - Imaging of oral cavity squamous cell carcinoma.

PMID- 18088847
TI  - Molecular biology and clinical behavior of oral cancer.

PMID- 18088848
TI  - Oral cancer prevention.

PMID- 18088849
TI  - Verrucous carcinoma.

PMID- 18088850
TI  - Special considerations with floor of mouth and tongue cancer.

PMID- 18088851
TI  - Surgical management of the neck in oral cancer.

PMID- 18088852
TI  - Sentinel lymph node biopsy in the staging of oral cancer.

PMID- 18088853
TI  - Access surgery for oral cancer.

PMID- 18088854
TI  - Postablative reconstruction techniques for oral cancer.

PMID- 18088855
TI  - Chemoradiation therapy: the evolving role in head and neck cancer and its
      application to oral cavity tumors.

PMID- 18088856
TI  - Management of locoregional recurrence in oral squamous cell carcinoma.

PMID- 18088857
TI  - Interventional approaches to management of pain of oral cancer.

PMID- 18088858
TI  - End of life issues in oral cancer.

PMID- 18088860
TI  - Third molar removal: an overview of indications, imaging, evaluation, and
      assessment of risk.
AB  - Asymptomatic third molars may have associated periodontal pathology that may not
      be limited to the third molar region and have a negative impact on systemic
      health. Third molars should be considered for removal when there is clinical,
      radiographic, or laboratory evidence of acute or chronic periodontitis, caries,
      pericoronitis, deleterious effects on second molars, or pathology. Radiographic
      findings of extreme locations of impacted teeth, dense bone, dilacerated roots,
      large radiolucent lesions associated with impactions, and lower third molar
      apices in cortical inferior border bone are predictive of more complex surgery.
      Certain demographic and oral health conditions available to the surgeon before
      surgery and intraoperative circumstances are predictive of delayed recovery for
      health-related quality of outcomes and delayed clinical outcomes after third
      molar surgery.

PMID- 18088861
TI  - Extraction versus nonextraction management of third molars.
AB  - Surgical removal of impacted third molars is the most commonly performed
      procedure by oral and maxillofacial surgeons. The removal of diseased or
      symptomatic third molars has not been an issue of controversy. The risk of
      surgery and associated complications are justified and uniformly accepted by most
      surgeons when the teeth are associated with chronic or acute pathologic
      processes, including caries, nonrestorable teeth, fractured roots, resorption,
      associated pathologic conditions (cysts, tumors), periapical abscesses,
      odontogenic infections, osteomyelitis, removal before reconstructive or ablative
      surgery, and radiation therapy.

PMID- 18088862
TI  - General technique of third molar removal.
AB  - The most commonly performed surgical procedure in most oral and maxillofacial
      surgery practices is the removal of impacted third molars. Extensive training,
      skill, and experience allow this procedure to be performed in an atraumatic
      fashion with local anesthesia, sedation, or general anesthesia. The decision to
      remove symptomatic third molars is not usually difficult, but the decision to
      remove asymptomatic third molars is sometimes less clear and requires clinical
      experience. A wide body of literature (discussed elsewhere in this issue)
      attempts to establish clinical practice guidelines for dealing with impacted
      teeth. Data is beginning to accumulate from third molar studies, which hopefully
      will provide surgeons and their patients with evidence-based guidelines regarding
      elective third molar surgery.

PMID- 18088863
TI  - Office-based anesthesia.
AB  - The practice of office-based oral and maxillofacial surgery is continuously
      expanding and involves the management of a diverse population in regards to the
      surgical procedures performed within the office and the age and medical health of
      the patients treated within the office. Comfort, cooperation, and hemodynamic
      stability are critical to satisfactorily accomplishing the surgical procedure.
      Various anesthetic techniques are used, including local anesthesia, anxiolysis,
      analgesia and sedation, and general anesthesia. The topic is vast and too
      extensive to be fully discussed in this article. The intent of this article is to
      provide a discussion of some fundamental concepts that can optimize anesthetic
      safety and care.

PMID- 18088864
TI  - Management of the impacted canine and second molar.
AB  - The clinical management of impacted canine and second molars can be challenging
      and frustrating. Successful management requires a team approach with the
      orthodontist and general dentist. It is recommended to try to preserve these
      teeth. Proper orthodontic mechanics are necessary for long-term stability. The
      appropriate treatment plan results in a predictable, stable, and aesthetic
      result.

PMID- 18088865
TI  - Therapeutic agents in perioperative third molar surgical procedures.
AB  - Surgical extraction of third molars is one of the most common of all surgical
      procedures. The outcome of third molar surgery includes pain, trismus, edema,
      nausea, infection, and alveolar osteitis. The intent of this article is to
      provide a literature review and analysis of the various chemotherapeutic agents
      used to control, minimize, or eliminate these outcomes. Unfortunately, comparison
      of the published studies represents a tremendous challenge because of the
      variability in parameters and methods used for each study. A trend does exist
      among many of the current researchers, who realize that randomized, controlled,
      evidence-based research rather than personal experience is necessary to develop
      appropriate guidelines for using chemotherapeutic agents.

PMID- 18088866
TI  - Partial odontectomy.
AB  - The problem of inferior alveolar nerve involvement during the removal of lower
      third molars is a clinical and medicolegal issue. Because the results of damage
      to the inferior alveolar nerve are unpredictable in that many cases do recover
      but some do not, it is preferable to carry out a technique that may reduce the
      possibility of this involvement. The technique of coronectomy, partial
      odontectomy, or deliberate root retention is one such technique to protect the
      inferior alveolar nerve that has been studied in the past but does not currently
      enjoy a strong body of support. The technique of coronectomy is worthy of
      consideration in cases in which panorex radiograph and cone beam CT scanning show
      an intimate relationship between the roots of the mandibular third molar and the
      inferior alveolar nerve.

PMID- 18088867
TI  - Risk of periodontal defects after third molar surgery: an exercise in evidence
      based clinical decision-making.
AB  - This article's purpose is to apply evidence-based principles to answer the
      question: What is the risk of having persistent or new periodontal defects on the
      distal aspect of the mandibular second molar after third molar removal? Commonly,
      the second molar periodontal health either remains unchanged or improves after
      third molar removal. Eighteen weeks or more after third molar removal, 52% to
      100% of subjects had no change or improvement in attachment levels or probing
      depths. For subjects with healthy second molar periodontium preoperatively, the
      indication for third molar removal should be evaluated carefully because these
      patients have an increased risk for worsening of probing depths or attachment
      levels after third molar removal.

PMID- 18088868
TI  - Is there a role for reconstructive techniques to prevent periodontal defects
      after third molar surgery?
AB  - The purpose of this article is to address the following clinical question: Among
      subjects undergoing mandibular third molar (M3) removal, does an intervention at
      the time of tooth removal, when compared with no intervention, improve the long
      term periodontal health on the distal aspect of the adjacent second molar (M2)?
      Routine application of interventions to improve the periodontal parameters on the
      distal of the M2 at the time of M3 removal is not indicated for most subjects.
      There seems to be a subpopulation of subjects having M3s removed who are at
      increased risk for periodontal defects after M3 removal, pre-existing periodontal
      defects, and a horizontal or mesioangular impaction. In the clinical setting of
      all three risk factors being present, there seems to be a predictable benefit to
      treating the dentoalveolar defect at the time of extraction.

PMID- 18088869
TI  - Nerve injuries after third molar removal.
AB  - Trigeminal nerve injuries are a known complication of third molar surgery. This
      article reviews the diagnosis, assessment, classification, microsurgical
      management, and outcome assessment of trigeminal nerve injuries that result from
      third molar removal.

PMID- 18088870
TI  - Complications of third molar surgery.
AB  - This article addresses the incidence of specific complications and, where
      possible, offers a preventive or management strategy. Injuries of the inferior
      alveolar and lingual nerves are significant issues that are discussed separately
      in this text. Surgical removal of third molars is often associated with
      postoperative pain, swelling, and trismus. Factors thought to influence the
      incidence of complications after third molar removal include age, gender, medical
      history, oral contraceptives, presence of pericoronitis, poor oral hygiene,
      smoking, type of impaction, relationship of third molar to the inferior alveolar
      nerve, surgical time, surgical technique, surgeon experience, use of
      perioperative antibiotics, use of topical antiseptics, use of intra-socket
      medications, and anesthetic technique. Complications that are discussed further
      include alveolar osteitis, postoperative infection, hemorrhage, oro-antral
      communication, damage to adjacent teeth, displaced teeth, and fractures.

PMID- 18088871
TI  - Legal implications of third molar removal.
AB  - This article focuses on legal ramifications inherent in the management of
      impacted teeth. The initial section explores the potential problems associated
      with the care of impacted teeth that makes such treatment clinically challenging
      and legally risky. The next section discusses means of preventing or mitigating
      the injuries that can occur during or after impaction surgery. The final sections
      cover various strategies to consider should a problem occur or legal action seem
      imminent.

PMID- 18088872
TI  - Treatment of the female oral and maxillofacial surgery patient. Preface.

PMID- 18088873
TI  - Anesthetic issues and anxiety management in the female oral and maxillofacial
      surgery patient.
AB  - Gender differences in preoperative anxiety, perioperative pain experience, and
      physiologic responses to anesthesia exist. Pharmacokinetic and pharmacodynamic
      gender differences in anesthetic drugs are especially significant for propofol
      and nondepolarizing muscle relaxants. Nonobstetric anesthesia for the pregnant
      patient is briefly reviewed.

PMID- 18088874
TI  - Autoimmune disease and the female patient.
AB  - This article focuses on the pathogenesis of the gender gap of autoimmune disease.
      Specifically, the discussion characterizes the role of sex hormones in the immune
      response and a female predilection for the common diseases seen in daily practice
      (ie, lupus erythematosus, myasthenia gravis, and other autoimmune diseases). A
      comparison between the sexes, with respect to autoimmune disease mechanisms, is
      presented to give oral and maxillofacial surgeons a better insight as to the role
      of sex and successful surgical treatment outcomes in this population of patients.

PMID- 18088875
TI  - Etiology of oral cancer in the young patient: is tongue cancer becoming the other
      cancer in women?
AB  - The recently reported increase in the incidence of oral cancer in a younger
      population, especially in young women, in the absence of the traditional risk
      factors has raised concern. Of particular interest is the increased incidence of
      carcinoma of the tongue, which has been suggested to be a distinct entity.
      Although there are conflicting data on incidence and sex distribution, studies
      suggest that the physiologic response to risk factors by men and women and the
      clinical behavior of these cancers in the younger population may be different
      than the normal variant. Effort is currently being made to elucidate the etiology
      and pathogenesis of oral cancer in the younger population.

PMID- 18088876
TI  - Eating disorders in the female patient: pathophysiology and treatment strategies.
AB  - Eating disorders are common in girls and women. Two common eating disorders-
      anorexia nervosa and bulimia nervosa--have significant medical complications.
      Oral and maxillofacial surgeons must be cognizant of the signs, symptoms, and
      medical consequences of these disorders. The increased incidence of these
      diseases has implications in the surgical management the oral and maxillofacial
      surgery patient. A review of the literature and guidelines in the perioperative
      management of these surgical patients are presented in this article.

PMID- 18088877
TI  - Impact of postmenopausal osteoporosis on the oral and maxillofacial surgery
      patient.
AB  - With aging, there is a loss of skeletal mass in women and men, but the rate of
      loss accelerates in perimenopausal women. With the loss of bone mass there is
      increased risk for fracture in the axial and appendicular skeleton. The mandible
      and maxilla also experience age-related declines in some parameters of
      architecture and trabecular pattern, but those do not seem to be directly
      associated with fracture risk. Although the literature is controversial regarding
      the generalizability of the impact of systemic osteoporosis on the
      oral/maxillofacial patient, it is prudent to give consideration to an individual
      patient's osteoporosis status, risk, and anti-osteoporosis therapies when
      planning oral and maxillofacial surgical procedures.

PMID- 18088878
TI  - Osteonecrosis and bisphosphonates in oral and maxillofacial surgery.
AB  - Bisphosphonates are a class of compounds approved for the treatment of multiple
      myeloma, hypercalcemia of malignancy, osteolytic lesions of metastatic disease,
      Paget's disease, and most commonly, osteoporosis. Recently, these drugs have been
      associated with a new clinical entity, bisphosphonate related osteonecrosis
      (BRON) which is characterized by jaw necrosis that typically presents following
      dentoalveolar surgery. The pathogenesis for this complication appears to related
      to bisphosphonate mediated inhibition of osteoclast function and normal bone
      remodeling. This complication can have a significant impact on the quality of
      life for those patients with advanced stages of necrosis.

PMID- 18088879
TI  - Oral and maxillofacial surgery for the pregnant patient.
AB  - This article describes clinical approaches for the perioperative management of
      the pregnant oral and maxillofacial surgical patient. The following topics are
      discussed: ethical principles of treatment during pregnancy, physiologic changes
      and their treatment considerations, fetal and maternal risks of various
      medications, medical problems occurring during pregnancy, and common minimally
      invasive approaches that the surgeon can apply to minimize the risk to the mother
      and unborn child. The strategies discussed provide successful treatment outcomes
      during this important time in the female surgical patient's life.

PMID- 18088880
TI  - Condylar resorption.
AB  - Idiopathic condylar resorption almost exclusively affects women. Its exact
      etiology and pathogenesis remain unclear. It has been associated with rheumatoid
      arthritis, temporomandibular joint internal derangement, condylar fractures,
      connective tissue or autoimmune diseases, orthodontic treatment, and orthognathic
      surgery. In most cases, however, there is no identifiable precipitating event,
      hence the term "idiopathic condylar resorption." The female predisposition to
      this condition may be attributed to the influence of estrogen and prolactin on
      the bone response. Treatment of idiopathic condylar resorption is controversial.
      Condylectomy and reconstruction with costochondral graft offer definitive
      management of active idiopathic condylar resorption.

PMID- 18088881
TI  - Cosmetic surgery considerations in the female patient.
AB  - A greater number of women than men undergo facial cosmetic procedures. Oral and
      maxillofacial surgeons should have an in-depth knowledge of the physiologic and
      anatomic differences between the sexes with respect to surgical treatment
      options. Gender differences in regard to the planning and management of female
      cosmetic surgery patients are the focus of this article.

PMID- 18088882
TI  - Chronic facial pain in the female patient: treatment updates.
AB  - Over the past decade, gender-related differences in pain and analgesia have been
      examined in experimental settings with conflicting evidence on whether men and
      women differ in their response to pain. New advances in research have begun to
      investigate the influence of genetic factors in moderating sex differences in
      analgesic response. This article provides oral and maxillofacial surgeons with
      evidence-based data on the issues of chronic pain between the sexes to suggest
      alternative approaches to the management of pain in their male and female
      patients.

PMID- 18088883
TI  - The abused female oral and maxillofacial surgery patient: treatment approaches
      for identification and management.
AB  - Violence and abuse affect one in four women during their lifetime. Specifically,
      a woman seeking treatment of a facial injury has a one in three chance of being a
      victim of violence and abuse. Many dental professionals, however, are
      uncomfortable discussing these issues with potential victims. The oral and
      maxillofacial surgeon is in a unique position to approach the topic of violence
      and abuse. This article discusses violence and abuse as it pertains to the female
      patient and family members. Suggestions for screening and evaluation of patients
      are discussed. The overall importance of timely identification for stopping this
      cycle of violence and abuse and the obligations of health care providers are also
      addressed.

PMID- 18088884
TI  - Sexual dimorphism and temporomandibular disorders (TMD).
AB  - Numerous studies suggest a sexual predilection for temporomandibular disorders.
      The purpose of this article is to review and summarize patient-oriented and basic
      science studies that address the topic of a female predilection for
      temporomandibular disorders. The information presented provides oral and
      maxillofacial surgery practitioners with evidence-based data to suggest a female
      predilection for temporomandibular disorders based on biologic, genetic, and
      behavioral/psychosocial factors.

PMID- 18088886
TI  - Three-dimensional imaging for virtual assessment and treatment simulation in
      orthognathic surgery.
AB  - Conventional two-dimensional imaging for assessing and treatment planning
      orthognathic surgery has limitations. Three-dimensional imaging offers the
      ability to more accurately portray maxillofacial anatomy. Three-dimensional CT
      based models can be generated for assessment of the dentofacial deformity.
      Interactive software can simulate surgical moves and algorithms can predict the
      three-dimensional soft tissue changes that will occur. This will inevitably
      effect diagnosis and treatment planning for orthognathic surgery in the future.

PMID- 18088887
TI  - Stability of orthognathic surgery and distraction osteogenesis: options and
      alternatives.
AB  - Relapse in orthognathic surgery is multifactorial and can be attributed to
      posttreatment growth, condylar changes, lack of rigid fixation, and muscle pull
      and function. Consideration of these factors can aide the surgeon in the decision
      making process with regards to treatment options and alternatives. This article
      reviews the stability of various orthognathic movements using traditional
      osteotomies and fixation, and compares them to what is currently in the
      literature regarding distraction osteogenesis.

PMID- 18088888
TI  - Anterior open bite correction by Le Fort I or bilateral sagittal split osteotomy.
AB  - Some of the most challenging dentofacial deformities facing surgeons and
      orthodontists are anterior open bite malocclusions. Determining the cause for the
      development of an anterior open bite and formulating a diagnosis are complicated
      by the role of neuromuscular and genetic influences. Long-term skeletal and
      dental stability has been a concern because of the influence that the
      neuromusculature has on the repositioned jaws and stability of teeth after
      vertical orthodontic mechanics required for closing open bites.

PMID- 18088889
TI  - Correction of skeletal open bite with implant anchored molar/bicuspid intrusion.
AB  - Implant-anchored orthodontics is a rapidly developing new field in the treatment
      of major malocclusion. In particular, the use of skeletal fixtures as orthodontic
      anchors is affording a minimally invasive treatment option for correction of
      skeletal anterior open bite as an alternative to major surgery. This article
      reviews the literature and guides oral and maxillofacial surgeons and
      orthodontists in case selection and management of open bite with implant-assisted
      orthodontics.

PMID- 18088890
TI  - Maxillary transverse deficiency - surgical alternatives to management.
AB  - Management of transverse maxillary discrepancies poses treatment planning and
      postoperative challenges for surgeons and orthodontists. Multiple position papers
      have been written on the subject covering various aspects of nonoperative and
      surgical treatment and timing and stability issues. This article seeks not to
      propagate the debate of which procedure is better but rather to discuss
      appropriate indications for each in addition to their respective benefits and
      pitfalls. An historical perspective and the technical aspects of performing each
      operation are reviewed.

PMID- 18088891
TI  - Anterior segmental mandibular osteotomies for the correction of facial-skeletal
      deformities.
AB  - Although an anterior segmental osteotomy of the mandible was the first
      orthognathic procedure described in the literature, there little material has
      been published since that time. Currently, because of cooperation between
      orthodontists and surgeons, only a few of these procedures can be used routinely.
      These procedures include the midline ostectomy and the midline osteotomy, which
      are normally done in conjunction with ramus osteotomies. Indications for and the
      techniques of these two procedures are covered.

PMID- 18088892
TI  - Skeletal surgery for airway issues.
AB  - Skeletal surgeries, specifically orthognathic procedures are an integral part of
      the treatment regimen for patients with airway issues. As evaluation mechanisms
      for, research into, and treatment options for, patients with airway issues have
      become refined, so have the techniques used to treat them become more focused and
      less prescriptive. The diagnosis for the severity of the airway compromise has
      also undergone an evolutionary change, with the diagnostic criteria becoming more
      restrictive and the equipment for diagnosing them more sophisticated.

PMID- 18088894
TI  - Esthetic options with two jaw surgery.
AB  - Aesthetic changes are most frequently achieved by changing the underlying bony
      support to the facial skeleton. Aesthetic improvement may include additional
      procedures to mask or enhance the skeletal results. This article deals with
      aesthetic changes brought about by changes in the skeletal support of the face
      and focuses on movement of both jaws.

PMID- 18088893
TI  - Management of facial asymmetry.
AB  - Asymmetries of the craniofacial region encompass a multitude of diverse and
      potentially complex abnormalities that may be the result of numerous causes. The
      expression and degree of asymmetry for a given condition, although a highly
      variable process, is the ultimate determinant of the nature of its treatment.
      This article highlights some of the key features and treatment strategies for
      various common facial asymmetries.

PMID- 18088897
TI  - Bone and bone graft healing.
AB  - Bone is unique in connective tissue healing because it heals entirely by cellular
      regeneration and the production of a mineral matrix rather than just collagen
      deposition known as scar. This article discusses the cellular, tissue, and organ
      levels in each of the following sections--skeletal embryology, normal bone,
      examples of abnormal bone, and bone graft healing--as they relate to the jaws and
      the craniofacial skeleton.

PMID- 18088895
TI  - Aesthetic surgery to augment orthognathic surgery.
AB  - The purpose of this article is to discuss some of the more commonly performed
      aesthetic surgical procedures to augment the final outcome of orthognathic
      surgery. These procedures are divided into two categories: those that can safely
      and predictably be performed simultaneously with orthognathic surgery and those
      that ideally should be performed independently of orthognathic surgery. This
      latter category also includes camouflage surgery, which includes aesthetic
      surgical procedures that are performed to camouflage or mask underlying
      dentofacial deformities in patients who, for various reasons, are not candidates
      for traditional orthognathic surgery or prefer a "smaller" operation. Camouflage
      surgery may be an attractive alternative for this group of patients because it is
      usually a much smaller operation and has a shorter recovery period.

PMID- 18088898
TI  - Genetic disorders and bone affecting the craniofacial skeleton.
AB  - Genetic disorders of bone constitute a large number of alterations approaching
      almost 300 types. This article focuses on the most common disorders in this
      group, which at the same time are the most clinically significant because of
      their incidence and degree of involvement of the craniofacial skeleton.

PMID- 18088899
TI  - Role of the oral and maxillofacial surgeon in the diagnosis and treatment of
      patients with osteoporosis.
AB  - Because of the increasing prevalence of osteoporosis in the aging population, it
      is important for oral surgeons to be aware of this condition. Oral health
      frequently reflects systemic diseases, and calcium loss in the teeth may mirror
      systemic mineral losses in the skeleton. Chronic health conditions, such as
      osteoporosis, also may affect surgical outcomes. In the past, therapies of
      osteoporosis were limited to hormonal replacement therapy and fluoride. Recently,
      there has been a proliferation of new therapies for osteoporosis that may affect
      dental health. The association between bisphosphonate use and osteonecrosis of
      the jaw is of concern. It is important that oral surgeons be aware of the
      medications a patient is using for the treatment of osteoporosis before
      initiating any procedure.

PMID- 18088900
TI  - Bisphosphonates and bisphosphonate induced osteonecrosis.
AB  - Bisphosphonate-induced osteonecrosis of the jaws is the correct term for this
      real drug complication that most dental practitioners face. All nitrogen
      containing bisphosphonates pose a risk, which is related to the route of
      administration, the potency of the bisphosphonate, and the duration of use.
      Although intravenous bisphosphonate-induced osteonecrosis of the jaws is mostly
      permanent, most cases can be prevented or managed if they develop, with only a
      few cases requiring resection for resolution. Oral bisphosphonate-induced
      osteonecrosis of the jaws also can be prevented with knowledge of the risk level
      related to the duration of use and the C-terminal telopeptide blood test results.
      Most cases can be resolved with a drug holiday either spontaneously or via
      straightforward debridement.

PMID- 18088901
TI  - Bone replacement grafts for the treatment of periodontal intrabony defects.
AB  - Bone replacement grafts, including autogenous grafts from intraoral donor sites,
      allografts, xenografts, and alloplastic bone substitutes, are the most widely
      used treatment modalities for the regeneration of periodontal osseous defects.
      Studies suggest a favorable clinical outcome with the use of these materials in
      terms of improvements in periodontal probing depths, probing attachment gains,
      and bone fill. In terms of bone fill, most studies report more than 50%
      resolution of intrabony defects when treated with bone replacement grafts.
      However, histologic evidence of periodontal regeneration, including new bone,
      periodontal ligament, and cementum, has been reported only for autogenous bone
      grafts and demineralized freeze-dried bone allografts.

PMID- 18088902
TI  - A review of bone substitutes.
AB  - The use of bone grafts in the repair of defects has a long history of success,
      primarily with the use of autologous bone. With increasing technologic advances,
      researchers have been able to broaden the spectrum of grafting materials to
      allografts, xenografts, and synthetic materials, which provide the surgeon and
      patient with options, each with unique advantages. It is with the knowledge of
      each material that the clinician can present and suggest the best material and
      tailor treatment plans to fit each individual. In this article, we present an
      overview of the principles of bone grafting, the types of graft materials
      available, and an outlook to what the future holds in this area of medicine and
      dentistry.

PMID- 18088903
TI  - Contemporary concepts in the treatment of chronic osteomyelitis.
AB  - Although there are relatively standard treatment approaches for chronic
      osteomyelitis, many avenues of investigation are being pursued to reflect
      contemporary concerns. The mainstays of care continue to include timely and
      thorough surgical debridement and culture-directed antibiotics. Sensitive
      diagnostic screening is essential, and advances in radiology can lead to early
      confirmation of disease and accurate surveillance. There is potential to greatly
      reduce overall morbidity, chance of recurrent infection, and treatment courses by
      using the local delivery systems currently researched by orthopedic surgeons. The
      challenges posed by multidrug-resistant bacterium may be countered by sound
      culturing techniques and new antibiotics. The general purpose of this article is
      to survey the new directions in oral surgery, orthopedics, infectious disease,
      immunology, and radiology that may have application to the treatment of
      maxillofacial osteomyelitis.

PMID- 18088904
TI  - Bone morphogenetic proteins: a realistic alternative to bone grafting for
      alveolar reconstruction.
AB  - Preclinical studies have shown that rhBMP-2 induces normal physiologic bone in
      clinically relevant defects in the craniofacial skeleton. The newly formed bone
      assumes characteristics of the adjacent resident bone and allows placement,
      osseointegration/re-osseointegration, and functional loading of endosseous
      implants. Clinical studies optimizing dose, delivery technologies, and conditions
      for stimulation of bone growth will bring about a new era in dentistry. The
      ability to predictably promote osteogenesis through the use of bone morphogenetic
      protein technologies is not far from becoming a clinical reality and will have an
      astounding effect on how dentistry is practiced.

PMID- 18088905
TI  - Advances in head and neck radiotherapy to the mandible.
AB  - Management of radiation-exposed bone in the mandible is a dilemma many oral and
      maxillofacial surgeons must confront and manage. Current advances in radiotherapy
      techniques using pin-point computerized accuracy in combination with other
      advances, such as morphed imaging, fractionalization protocols, minimization of
      scatter, and pretreatment dental examinations, have greatly decreased the late
      effects of radiation and osteoradionecrosis. The intent of this article is to
      provide a brief overview of the following topics: radiotherapy physics and
      radiobiology, effects of radiotherapy on normal tissues, including the
      pathogenesis of osteoradionecrosis, and advances in contemporary radiotherapy
      treatment.

PMID- 18088906
TI  - Distraction osteogenesis: advancements in the last 10 years.
AB  - Distraction is still evolving in the management of patients with orthopedic and
      craniomaxillofacial deformities. The relationship among latency, gap size, rate,
      rhythm, and duration of fixation is not totally understood for all of the
      individual patients and variations in their needs seen in a clinical practice.
      Numerous factors can influence the quality and quantity of bone seen with
      distraction, including the age and nutritional status of the patient and the type
      of distractor that is used.

PMID- 18088908
TI  - Editorial.

PMID- 18088907
TI  - Bone morphogenetic proteins and the induction of bone formation: from laboratory
      to patients.
AB  - This article revisits the induction of bone by the osteogenic proteins of the
      transforming growth factor-beta superfamily in nonhuman and human primates and
      proposes that the translation in clinical contexts of the phenomenon of bone;
      formation by autoinduction, is predictably achievable by the binary application
      of relatively low doses of transforming growth factor-beta proteins with a
      recombinant human osteogenic protein. The synergistic induction of bone formation
      is a cost-effective clinical strategy because published data in nonhuman primates
      have shown that doses of recombinant human recombinant osteogenic protein-1 can
      be reduced at least fivefold and still increase bone formation compared with
      higher doses of single applications of human recombinant osteogenic protein-1.

PMID- 18088909
TI  - Respiratory system of arachnids I: morphology of the respiratory system of
      Salticus scenicus and Euophrys lanigera (Arachnida, Araneae, Salticidae).
AB  - The book-lungs and the tracheal systems of two species of jumping spider,
      Salticus scenicus and Euophrys lanigera, were investigated using gross
      anatomical, light and electron microscopic methods. Both species possess well
      developed book-lungs of similar size and tracheal systems with a basically
      similar branching pattern. The tracheal spiracle opens into a single atrium,
      where it gives rise to four thick 'tube tracheae', from which small secondary
      tube tracheae originate in groups. The secondary tracheae (diameter 1-5 mum) run
      parallel, without further branching, into the prosoma. In the opisthosoma, they
      lie ventrolaterally, where they contact muscles and internal organs. In the
      prosoma, the secondary tracheae may penetrate the gut epithelium and central
      nervous tissue. The structure of the tracheal walls is very similar to that of
      insects, consisting of a striated inner cuticular layer with taenidial structures
      and a surrounding outer hypodermal layer. The wall thickness appears similar in
      all secondary tracheae, indicating that lateral gas diffusion may be possible
      through the walls of all small tube tracheae.

PMID- 18088910
TI  - Respiratory system of arachnids II: morphology of the tracheal system of
      Leiobunum rotundum and Nemastoma lugubre (Arachnida, Opiliones).
AB  - The tracheal system of two species of harvestmen with different life styles was
      investigated: the long-legged, Leiobunum rotundum (Phalangioidea, Phalangiidae)
      and the short-legged Nemastoma lugubre (Troguloidea, Nemastomatidae). The
      morphology of the tracheae is very similar in both species: The branching pattern
      is basically asymmetric and dichotomous, and the tracheae taper between branching
      points. The tracheal diameters range from 160 to 0.3 mum in L. rotundum (mean
      body mass 25.3 mg), and from 70 to 0.5 mum in N. lugubre (mean body mass 3.8 mg).
      Ultrastructurally, the tracheal walls are similar to those of insects, consisting
      of an outer hypodermal layer and an inner cuticular layer with taenidial
      structures. Tracheae of all diameters have close contact with organs and muscles,
      indicating that diffusive gas exchange may take place through the walls of all
      tracheae. The finest tracheae end freely in the hemolymph or at the surface of
      organs and muscles. Exceptions are tracheal penetration of the central nerve mass
      in the prosoma in both species, and of the muscles in L. rotundum. The latter may
      correlate with the active perambulatory life style of L. rotundum.

PMID- 18088911
TI  - Detailed developmental morphology of the spermatophore of the Mediterranean field
      cricket, Gryllus bimaculatus (De Geer) (Orthoptera: Gryllidae).
AB  - The detailed developmental morphology of the spermatophore of a cricket (Gryllus
      bimaculatus, De Geer) is described for the first time. A specific behavioural
      reference point is identified from which time developmental processes proceed in
      a more or less robotic manner. The structures previously identified as forming
      part of the fully formed spermatophore, that is, the ampulla, the sperm tube and
      the attachment plate are all identified in detail during their development.
      Interestingly the attachment plate material is extruded as an amorphous mass from
      the ejaculatory duct prior to its insertion into the dorsal pouch, the sperm do
      not enter the sperm sac until the end of spermatophore formation, and the sperm
      tube itself is formed from a flattened layer of material which rolls up into a
      tube and involves the use of a die mechanism.

PMID- 18088912
TI  - Morphology of antennal sensilla auricillica and their detection of plant
      volatiles in the Herald moth, Scoliopteryx libatrix L. (Lepidoptera: Noctuidae).
AB  - In the Herald moth Scoliopteryx libatrix there are single superficial auricillic
      sensilla, as well as groups of s. auricillica located in cavities on the
      antennae. Two sensory neurones, with different dendrite diameters innervate each
      of these sensilla. The diameter of the smaller dendritic segment is roughly half
      that of the larger one. The larger dendritic outer segment branches profusely in
      the lumen of the sensillum, whereas the smaller dendrite has few branches.
      Electrophysiological recordings from s. auricillica located in the medial part of
      the cavity revealed a receptor neurone responding to Delta-3-carene. In addition
      to these neurones, recordings made deeper and more laterally into the cavity
      showed neurones that responded to (+/-)-linalool, alpha-pinene and green leaf
      volatiles.

PMID- 18088913
TI  - Ultrastructure and physiology of the CO2 sensitive sensillum ampullaceum in the
      leaf-cutting ant Atta sexdens.
AB  - The sensilla ampullacea on the apical antennomere of the leaf-cutting ant Atta
      sexdens were investigated regarding both their responses to CO2 and their
      ultrastructure. By staining the sensillum during recording, we confirmed that the
      sensilla ampullacea are responsible for CO2 perception. We showed that the
      sensory neurons of the sensilla ampullacea are continuously active without
      adaptation during stimulation with CO2 (test duration: 1 h). This feature should
      enable ants to assess the absolute CO2 concentration inside their nests. Sensilla
      ampullacea have been found grouped mainly on the dorso-lateral side of the distal
      antennal segment. Scanning and transmission electron microscopic investigations
      revealed that the external pore opens into a chamber which connects to the
      ampulla via a cuticular duct. We propose protection against evaporation as a
      possible function of the duct. The ampulla houses a peg which is almost as long
      as the ampulla and shows cuticular ridges on the external wall. The ridges are
      separated by furrows with cuticular pores. The peg is innervated by only one
      sensory neuron with a large soma. Its outer dendritic segment is enveloped by a
      dendritic sheath up to the middle of the peg. From the middle to the tip numerous
      dendritic branches (up to 100) completely fill the distal half of the peg. This
      is the first report of a receptor cell with highly branched dendrites and which
      probably is tuned to CO2 exclusively.

PMID- 18088914
TI  - Immunolocalization of general odorant-binding protein in antennal sensilla of
      moth caterpillars.
AB  - Antennae of Bombyx mori and Helicoverpa armigera larvae were immunolabelled with
      antisera raised against the pheromone-binding protein or the general odorant
      binding protein 2 of Antheraea polyphemus to assign the expression of these
      proteins to individual sensilla and to compare the localization pattern with that
      in sensilla of adult moths. Specific labelling of antennal sensilla was only
      obtained with the antiserum against general odorant-binding protein 2. Among the
      few sensilla present on the antenna the three large sensilla basiconica, which
      are suspected to be olfactory in function, were labelled. These sensilla are
      compound sensilla consisting of several sensillum units which form a common
      sensory hair. The hair is single-walled and pierced by many pores. Labelling of
      sensillum compartments was the same as in sensilla of adults. Prominent labelling
      of the sensillum lymph is accompanied by labelling of secretory organelles in the
      two outermost auxiliary cells and of endocytotic pathways in all sensillum cells.
      The results suggest that general odorant-binding protein is expressed in single
      walled multiporous sensilla of presumed olfactory function on the antenna of moth
      larvae. The overall identity of the localization pattern for general odorant
      binding protein between larval and adult sensilla implies a similar role of these
      proteins in olfactory stimulus transduction.

PMID- 18088915
TI  - Identification of resilin in the leg of cockroach, Periplaneta americana:
      confirmation by a simple method using pH dependence of UV fluorescence.
AB  - We have examined the tarsus (foot) and tibial segments of the cockroach leg to
      identify structures that contain the elastic protein resilin. The presence of
      resilin was tested using the conventional criteria of fluorescent emission at 420
      nm under UV illumination and histological staining of wholemount tissues by
      toluidine blue. We have also developed a simple method of confirming
      identification of resilin through changes in its fluorescence that occur with
      alteration of pH of the surrounding medium. Using a commonly available excitation
      filter that only passes light at >330 nm, we found that the emission was present
      at neutral pH but was eliminated at low pH. It then reversibly reappeared when
      medium of higher pH was restored. This effect is attributable to a known shift in
      the absorption maximum of amino acids of resilin that occurs in acidic media
      (from 330 to 285 nm). The accuracy of this method of identification was confirmed
      by examination of ligaments of the wing hinge, which has previously been shown to
      contain resilin in a number of insects. Using these techniques, we have
      identified resilin in association with ligaments at the tibio-tarsal joint and in
      the articulation between the fourth and fifth tarsal segments of the leg. The
      anatomical arrangement of these ligaments suggests that they could aid in the
      generation of leg movements during walking by functioning as elastic antagonists
      to the actions of leg muscles. The method of identification we have devised could
      readily be applied to aid in the localization of resilin in other animals.

PMID- 18088916
TI  - NADPH diaphorase and nitric oxide synthase in the corpus cardiacum-corpus allatum
      of the cockroach Diploptera punctata.
AB  - Juvenile hormone synthesis by corpora allata is regulated partly by allatostatin
      containing nerves from the brain that innervate the corpora cardiaca and the
      corpora allata. To investigate whether NO also participates in the regulation of
      juvenile hormone synthesis, antibody against NO synthase and the histochemical
      test for NADPH diaphorase activity, a marker for NO synthase, were applied to the
      corpora cardiaca-corpora allata of Diploptera punctata. Strong NADPH diaphorase
      activity occurred in corpus allatum cells but not in nerve fibers in the corpora
      allata or corpora cardiaca. In contrast, NO immunoreactivity occurred in nerves
      in the corpora cardiaca but not within the corpora allata. NO and allatostatin
      were not colocalized. NO synthase and NADPH diaphorase activity were localized in
      similar areas of the subesophageal ganglion and cells in the pars intercerebralis
      of the brain. Positive correlation of the quantity of NADPH diaphorase activity
      with juvenile hormone synthesis during the gonadotrophic cycle and lack of such
      correlation in subesophageal ganglia suggest that NADPH diaphorase activity
      reflects the necessity of NADPH in the pathway of juvenile hormone synthesis.
      These data suggest that NO is unlikely to play a significant role in the
      regulation of the corpora allata.

PMID- 18088917
TI  - An unusual case of a mutant lobster embryo with double brain and double ventral
      nerve cord.
AB  - We report the rare finding of a Siamese twin embryo of the American lobster
      Homarus americanus. Immunohistochemical labeling of this mutant with an antibody
      directed against Drosophila synaptic proteins revealed that the embryo had a
      structurally normal visual system with two compound eyes and eyestalk Anlagen but
      twin brains and twin ventral nerve cords. We have analyzed the patterns of
      connectivity of the components of the nervous system and have concluded that the
      wiring pattern in this nervous system provides a logical and elegant way of
      connecting the parts of the twin system in this unusual mutation.

PMID- 18088918
TI  - Evidence of age-related changes in the antennal glomeruli of Drosophila
      melanogaster using monoclonal antibodies.
AB  - As a tool to better understand the organization of the olfactory pathway three
      monoclonal antibodies have been isolated and characterized each having a unique
      staining pattern in the antenna and antennal lobe of Drosophila melanogaster.
      Monoclonal antibody F14-2D6 stains sensilla coeloconica and thick sensilla
      basiconica in the funiculus, Y1-3D10 stains only a few sensilla especially in and
      around the sacculus, while F15-12E8 stains all the sensilla. All three antibodies
      stain a subset of the glomeruli in the antennal lobe, of which 11 glomeruli are
      stained in common by all three antibodies. These antibodies could be used to
      study projection patterns of the sensilla into the antennal lobe. Glomerular
      staining was observed at different developmental times with the different
      antibodies. F15-12E8 stains all the glomeruli at eclosion, Y1-3D10 stains only a
      few glomeruli at eclosion but most glomeruli are stained by the first day after
      eclosion. F14-2D6 stains all glomeruli only after eclosion. F15-12E8 also stains
      the mushroom bodies. The antigen recognized by F14-2D6 in the glomeruli shows an
      increase with age of the flies, measured as increased intensity of staining.
      These observations suggest that age-related changes continue in the antennal lobe
      of the flies even after eclosion. These antibodies could therefore serve as
      unique markers for other studies on the development of the olfactory system.

PMID- 18088919
TI  - The juvenile hormone analog pyriproxyfen affects ecdysteroid-dependent cuticle
      melanization and shifts the pupal ecdysteroid peak in the honey bee (Apis
      mellifera).
AB  - The control of the pupal melanization in the honey bee by ecdysteroids, and the
      modulation of these processes by a juvenile hormone analog were investigated by a
      combination of in vivo and in vitro experiments. Injection of 1-5 microg of 20
      hydroxyecdysone (20E) into unpigmented pupae showed a dose- and stage-dependent
      effect. The higher the dose and the later the injection was performed, the more
      pronounced was the delay in cuticle pigmentation. This inhibition of cuticular
      melanization by artificially elevated ecdysteroid titers was corroborated by in
      vitro experiments, culturing integument from unpigmented, dark-eyed pupae for 1-4
      days in the presence of 20E (2 or 5 microg/ml culture medium). Topical
      application (1 microg) of pyriproxyfen to unpigmented, white-eyed pupae had the
      opposite effect, leading to precocious and enhanced melanization of the pupal
      cuticle. In vitro incubation of integuments in the presence of this juvenile
      hormone analog (1 microg/ml) confirmed these results, showing that pyriproxyfen
      is apparently capable of triggering melanization. The in vivo mode of action of
      pyriproxyfen was further investigated by quantifying hemolymph ecdysteroids by
      radioimmunoassays. Topical application leads to a delay of the pupal ecdysteroid
      peak by 4 days. The pyriproxyfen-induced low ecdysteroid titers during early
      pupal development could account for precocious pigmentation by removing an
      inhibition on prophenoloxidase activation normally imposed by the elevated
      ecdysteroid titer during this phase.

PMID- 18088920
TI  - Ultrastructure of pheromone-detecting sensillum placodeum of the Japanese beetle,
      Popillia japonica Newmann (Coleoptera: Scarabaeidae).
AB  - The pheromone-detecting sensilla placodea are significantly more numerous than
      other sensory structures in the antennae of the Japanese beetle, Popillia
      japonica (Coleoptera: Scarabaeidae). Their abundance in males is nearly twice of
      that in females, showing a clear sexual dimorphism. Externally, they have a
      tortoise shell-like round cuticular plate containing a few polygonal plates
      separated by narrow ridges. Internally, they house two long dendrites that branch
      and terminate near fine cuticular pores. They have a system of two bipolar
      neurons accompanied by three enveloping cells, resembling sensilla trichodea in
      moths. The conspicuous difference with the latter is that the sensillum-lymph
      cavity near the outer cuticle is funnel-shaped, into which the tormogen cell
      projects numerous microvilli whose tips approach the terminal branches of the
      dendrites.

PMID- 18088921
TI  - Microsculpture of the wing surface in Odonata: evidence for cuticular wax
      covering.
AB  - The insect wing membrane is usually covered by scales, hairs, and acanthae, which
      serve diverse functions, such as species-specific coloration pattern, decrease of
      wind resistance during flight or decrease of wing wettability. Representatives of
      Palaeoptera (Odonata and Ephemeroptera) have no hairy structures on the wing
      membrane, but both its sides are fine-sculptured. In this study, the nature of
      the wing covering was studied using acoustic microscopy, scanning- and
      transmission electron microscopy followed by a variety of chemical treatments. It
      was shown that wing microsculptures are not cuticular outgrowths, but a wax
      covering, which is similar to pruinosity, which has been previously described in
      several odonate taxa. Data from scanning acoustic microscopy revealed that
      scratches on the wax covering have material density different from the
      surrounding material. Various functions of the wax covering are discussed.

PMID- 18088922
TI  - Elastic joints in dermapteran hind wings: materials and wing folding.
AB  - Representatives of Dermaptera probably have the most unusual hind wing venation
      and folding pattern among insects. Both correlate with unusual wing folding
      mechanics, in which folding is achieved from within the wing and unfolding is
      done by the cerci. In this account, the hind wings of the earwig Forficula
      auricularia were studied by means of bright field and fluorescence microscopy.
      Resilin, a rubber-like protein, was revealed in several, clearly defined patches.
      It occurs dorsally in the radiating veins, but ventrally in the intercalary vein.
      This distribution determines the folding direction, and resilin is the major
      driving mechanism for wing folding. Resilin stores elastic energy in broadened
      vein patches and along the folds. At the other locations, the mid-wing mechanism
      and central area, the primary function of resilin is suggested to be prevention
      of material failure. The arrangement of resilin patches is such that the wing
      cannot be unfolded from the thorax proper but must be unfolded by the cerci. In
      Dermaptera, the antagonistic movements of folding and unfolding are achieved in
      two different ways, resilin and cerci. To our knowledge this is unique.

PMID- 18088923
TI  - Biomechanics of the multisclerite middle coxa in flies (Diptera).
AB  - The middle coxa in Calliphora consists of three sclerites. Two rear sclerites are
      able to rotate relative to the front sclerite about the intracoxal axis (ICA).
      The turn ahead about ICA puts the leg in a peculiar position with minimal
      aerodynamic resistance. Sclerites are articulated in a form of complex kinematic
      chain. Distances between articulations were measured; using them, various
      configurations of the model coxa were obtained by geometrical synthesis, the turn
      about ICA was simulated, and the muscle driving the turn ahead was revealed (the
      hind elevator). The middle leg with the complex coxa in most of Brachycera is
      specialised for the advanced flight performance.

PMID- 18088924
TI  - Two distinctly different sperm storage organs in female Dysdera erythrina
      (Araneae: Dysderidae).
AB  - The haplogyne spider D. erythrina possesses two distinctly different sperm
      storage organs: a bilobed anterior spermatheca and a large, sac-like posterior
      diverticulum. The glandular equipment of both storage types is markedly
      different: the glandular tissue of the spermatheca is composed of complicated
      glandular units comprising a cuticular ductule and three canal cells (class 3
      cells) whereas the glandular tissue of the posterior diverticulum is composed of
      simple gland cells that discharge their product through the cuticle (class 1
      cells). Thus, the glandular products produced differ, leading to different
      storage conditions for the spermatozoa from copulation to egg laying. It is
      suggested that multiple organ types have evolved to facilitate specialization in
      short-term and long-term storage and to allow (posterior diverticulum) or prevent
      (spermatheca) males from accessing previously stored sperm.

PMID- 18088925
TI  - Regional and functional differentiation in the fat body of pharaoh's ant queens,
      Monomorium pharaonis (L.).
AB  - The insect fat body is generally described as a uniform tissue with multiple
      functions, but we have found evidence of cell differentiation in the Monomorium
      fat body. We show that the fat body of a mature egg-laying pharaoh's ant queen is
      a result of a preceding remodeling of cell material comprising at least 11
      different fat cell types, located at specific positions in the head, alitrunk
      (thorax) and gaster (abdomen). The cell types are classified based on their
      position, histochemistry, ultrastructure, and immunoreactivity for
      vitellogenin/vitellin. Some of these cells are primordial cells present at
      emergence, others invade the histolysing flight muscle tissue, and still others
      disappear during the maturation process. Only one type, the subepidermal fat cell
      of the gaster, is active in vitellogenin synthesis and is the only cell type in
      close association with oenocytes. Although only this type produces vitellogenin,
      our material indicates that most fat cell types are essential to support egg
      production. In some queens vitellogenin was found to form crystals in ventral
      vitellogenin-producing fat cells. This indicates an imbalance between
      vitellogenin production in the fat cells and uptake in the oocytes, which is
      probably related to a cyclic regulation of egg production.

PMID- 18088926
TI  - The tracheal system of the developing primary olfactory pathway of Manduca sexta:
      tracheae do not play a guidance or targeting role for ingrowing receptor axons.
AB  - Axons navigate to their targets by detecting signals within the environment
      through which they are growing. The surfaces of tracheae, which are prominent
      features of the insect body plan, could be detected as favorable pathways for
      sensory axons growing toward the brain. The pattern of the tracheal investment of
      the adult antennal lobe of the moth Manduca sexta suggested two specific
      possibilities for interaction between tracheae and axons during development: that
      tracheae might be involved in guiding olfactory receptor axons to their target
      region of the brain, the antennal lobe; and that tracheae could provide an
      address system within the lobe that defines the sites of glomeruli, which are
      olfactory-axon target areas within the lobe. To determine whether tracheae
      contribute to development of the primary olfactory pathway, the distribution of
      tracheae in the adult and developing antennal lobes was examined with both
      confocal and electron microscopes. During the major stages in which axons are
      growing into the antennal lobe and in which glomeruli are forming, the tracheal
      investment of the nerve and lobe was found to be minimal. Tracheae thus cannot
      serve as axon guides or as local address sites for newly forming glomeruli during
      the initial targeting of receptors onto the antennal lobe.

PMID- 18088927
TI  - Onychophoran cephalic nerves and their bearing on our understanding of head
      segmentation and stem-group evolution of Arthropoda.
AB  - The extant Onychophora are basal representatives of the Arthropoda, resembling
      Cambrian arthropod stem-group fossils such as Aysheaia and other so-called
      lobopodians. They thus provide an important model system for early stages in
      arthropod evolution, especially those of the head. However, homologies between
      onychophoran and euarthropod head structures have remained uncertain, and
      previous descriptions of the onychophoran head are contradictory. Our
      investigation examines the cephalic nerves of two species of onychophoran using
      immunohistochemical and confocal laser scanning microscopical techniques. Our new
      reconstruction for the distribution of onychophoran cephalic nerves differs
      significantly from previous accounts. The so-called "labrum" of the Onychophora
      appears to be part of the pharynx, and any affinities to the various pre-oral
      outgrowths of crown-group arthropods referred to as hypostomata and/or labra can
      be ruled out. The innervation of the mouth is particularly noteworthy, as its
      nerves originate from three different regions of the brain, including the dorsum.
      This suggests that the mouth was primitively terminal/frontal, although
      subsequent ventral rotation of the mouth may have been parallelly achieved in
      Onychophora and in Euarthropoda. Our model allows the onychophoran cephalic
      nervous system to be interpreted as a modified circumoral nerve ring, similar to
      that seen in the nematodes and other cycloneuralians. We regard this as
      supporting the Ecdysozoa model of arthropod relationships.

PMID- 18088928
TI  - Atlas of olfactory organs of Drosophila melanogaster 2. Internal organization and
      cellular architecture of olfactory sensilla.
AB  - Antennae and maxillary palps of Drosophila melanogaster were studied with the
      electron microscope on serial sections of cryofixed specimens. The number of
      epidermal cells roughly equals the number of sensilla, except for regions where
      the latter are scarce or absent. Each epidermal cell forms about two non
      innervated spinules, a prominent subcuticular space and a conspicuous basal
      labyrinth, suggesting a high rate of fluid transport through the sensory
      epithelium. The internal organization and fine structure of trichoid,
      intermediate and basiconic sensilla is very similar. Receptor cell somata are
      invested by thin glial sheaths extending distad to the inner dendritic segments.
      Further distally, the thecogen cell forms a sleeve around the dendrites, but an
      extracellular dendrite sheath is absent. At the base of the cuticular apparatus,
      the inner sensillum-lymph space around the ciliary and outer dendritic segments
      is confluent with the large outer sensillum-lymph space formed by the trichogen
      and tormogen cells. All three auxiliary cells exhibit many features of secretory
      and transport cells but extend only thin basal processes towards the haemolymph
      sinus. The bauplan and fine structure of coeloconic sensilla differs in the
      following aspects: (1) the ciliary segment of the dendrites is located deeper
      below the base of the cuticular apparatus than in the other sensillum types; (2)
      a prominent dendrite sheath is always present, separating inner and outer
      sensillum-lymph spaces completely; (3) the apical microlamellae of the auxiliary
      cells are more elaborate, but free sensillum-lymph spaces are almost absent; (4)
      there are always four not three auxiliary cells. Morphometric data are presented
      on the diameter of inner and outer dendritic segments and on the size of receptor
      cells, as well as of the receptor and auxiliary cell nuclei. The special fine
      structural features of Drosophila olfactory sensilla are discussed under the
      aspects of sensillar function and the localization of proteins relevant for
      stimulus transduction.

PMID- 18088929
TI  - Functional morphology of antennal chemoreceptors of the parasitoid Microplitis
      croceipes (Hymenoptera: Braconidae).
AB  - The specialist parasitoid, Microplitis croceipes (Cresson) (Hymenoptera:
      Braconidae), uses chemical cues from plants damaged by herbivore-feeding and also
      plant by-products in host location and acceptance. These chemicals are detected
      by the wasp's antennae. We conducted scanning and transmission electron
      microscopy studies of male and female M. croceipes antennae and detected no
      distinct morphological differences in the chemoreceptors between the sexes. Male
      antennae are approximately twice as long as female antennae. We found five
      morphological sensillar types in both sexes: sensilla (s) trichodea were the most
      abundant and distributed over the whole antenna; s. chaetica were present in low
      numbers only on the scape and pedicel; and s. basiconica, s. coeloconica and
      elongated s. placodea were found only on the flagellum. Ultrastructural
      investigations revealed pore systems on s. basiconica and s. placodea. In s.
      placodea, sensory neurons run parallel to the longitudinal axis of the sensilla
      with terminal pores. We recorded responses from single olfactory receptor neurons
      in s. placodea to two plant-emitted volatiles, cis-3-hexenol and ocimene, and two
      anthropogenic compounds, cyclohexanone and 2-diisopropylaminoethanol. Male
      receptor neurons were more sensitive than those of females with significantly
      higher spike frequency being registered from neurons in males.

PMID- 18088930
TI  - Morphometric analysis of the calcium-transporting sternal epithelial cells of the
      terrestrial isopods Ligia oceanica, Ligidium hypnorum, and Porcellio scaber
      during molt.
AB  - Isopods shed first the posterior and then the anterior half of the body. Before
      molt, most terrestrial species resorb CaCO3 from the posterior mineralized
      cuticle. The mineral is stored in anterior sternal deposits, which are used to
      calcify the new posterior cuticle after molt. For Porcellio scaber it is known
      that the anterior sternal epithelium has specific structural differentiations for
      epithelial transport. These differentiations include the plasma membrane surface
      areas, and the volume fraction of the mitochondria. We analyzed the
      ultrastructure of the sternal epithelium and used a morphometric approach to
      study the variations of these parameters between species living in different
      terrestrial environments. In Ligidium hypnorum, which lives in moist
      environments, the plasma membrane surface area and volume fraction of
      mitochondria are much larger than in the semiterrestrial Ligia oceanica. This is
      in accordance with the relatively larger CaCO3 deposits and shorter time
      intervals for their formation and resorption in L. hypnorum. For P. scaber, which
      is adapted to mesic habitats, most values are between those of L. oceanica and L.
      hypnorum. However, P. scaber has even larger CaCO3 deposits which are formed and
      degraded within similar time intervals as in L. hypnorum. This unexpected result
      is considered from the standpoint of more effective mechanisms being present for
      epithelial ion transport.

PMID- 18088931
TI  - Morphology and ultrastructure of a specialized bacterial pouch in the digestive
      tract of Tetraponera ants (Formicidae, Pseudomyrmecinae).
AB  - The digestive tract in workers of some species of the pseudomyrmecine ant genus
      Tetraponera is characterized by a conspicuous pear-shaped diverticulum at the
      transition between the midgut and the intestine, that so far has not been found
      in any other ant species. As this organ is filled with a mass of bacteria, we
      propose to designate it as a bacterial pouch. Its distal wall is formed by a thin
      ectodermal epithelium, through which tens of tracheal branches penetrate into the
      bacterial mass that fills the pouch lumen. The proximal wall, in contrast, is
      formed by a cylindrical epithelium with a conspicuous microvillar differentiation
      of the apical cell membrane, but without a cuticular lining. The contact region
      between both epithelia occurs as a complex fold surrounding the pouch like a
      belt. The Malpighian tubules open into the pouch through the cylindrical
      epithelium adjacent to the belt fold. The functional significance of the
      bacterial pouch remains unknown, although the abundant presence of bacteria may
      indicate a symbiotic function. The conspicuous tracheolar supply illustrates the
      metabolic activity in the pouch, while the microvillar differentiation of the
      cylindrical epithelium may be interpreted in the uptake of metabolites from the
      pouch lumen.

PMID- 18088932
TI  - Building the antennal lobe: engrailed expression reveals a contribution from
      protocerebral neuroblasts in the grasshopper Schistocerca gregaria.
AB  - The expression pattern of the engrailed protein was studied in neuroblasts which
      delaminate at the border of the protocerebrum and antennal lobe of the
      deutocerebrum in the early embryonic brain of the grasshopper. The antennal lobe
      is a complex structure comprising both glomerular and non-glomerular components,
      a cellular organization which distinguishes it from the striate-like neuropil
      comprising the remainder of the deutocerebrum. Early in embryogenesis engrailed
      expression in the protocerebrum is restricted to a compact block of neuroblasts
      located at its interface with the antennal lobe. Subsequently engrailed
      expression in these cells disappears in a stepwise manner from anterior to
      posterior so that by 37% of embryogenesis only a single row of three engrailed
      positive neuroblasts and their progeny remains. Contemporaneously engrailed
      expression reappears in a group of more anterior progeny deriving from
      neuroblasts which are no longer immunoreactive. The three remaining engrailed
      positive neuroblasts then become separated from their non-immunoreactive
      neighbours by an invagination of the perineurium called the lateral cleft and
      come to lie completely within the developing antennal lobe. These cells then
      direct columns of immunoreactive progeny centrifugally towards the centre of the
      lobe. Such a protocerebral contribution to the antennal lobe suggests that the
      evolution and ontogeny of this brain region need to be reconsidered.

PMID- 18088933
TI  - Mechanoreceptors in calanoid copepods: designed for high sensitivity.
AB  - The mechanoreceptors of the first antennae of Pleuromamma xiphias, a mesopelagic
      calanoid copepod, are critical for the detection of potential threats. These
      receptors exceed the physiological performance of other crustacean
      mechanoreceptors in sensitivity to water velocities as well as in frequency
      response. A study of these receptors was initiated to elucidate structure
      function relationships. Morphologically, the receptors resemble the arthropod
      scolopidial organs by the presence of a scolopale tube. However, the rigidity of
      the copepod receptors greatly exceeds those described for crustaceans and other
      arthropods. The scolopale tube completely encloses the distal dendrites and it is
      firmly anchored to the cuticle. Microtubules are organized in register and arise
      from microtubule subfibers associated with crescent-shaped rods which extend from
      the basal body region to the setal socket. The distal dendrites are filled with a
      large number of cross-linked microtubules. Termination of the distal dendrites
      inside the lumen of the setae is gradual with a firm anchoring to the cuticle. A
      likely mechanism for mechanotransduction would involve a linkage between
      individual microtubules and mechano-gated channels in the dendritic membrane. The
      rigidity probably contributes to the high frequency sensitivity, and termination
      of the dendrite inside the seta increases the overall sensitivity of these
      receptors.

PMID- 18088934
TI  - A new type of arthropod photoreceptor.
AB  - A new type of photoreceptor for the phylum Arthropoda, found in the class
      Collembola (Arthropoda, Hexapoda) is reported. This new light-sensitive structure
      consists of a pair of interocular vesicles present in the genus Vesicephalus
      Richards, 1964 and is anatomically related to the cluster of ommatidia. The
      absence of a lens, the presence of a rabdome in the upper part of the vesicle and
      the reflection and refraction of light by a hemolymph bubble with incidence to
      the rhabdomeric structure are the main traits of this new photoreceptor.

PMID- 18088935
TI  - The maxillary palp sensory pathway of Orthoptera.
AB  - Primary sensory projections and arborisations of higher-order neurons associated
      with the maxillary palps were examined in Tettigoniidae, Gryllidae, Tetrigidae
      and Acrididae representing the two sub-orders of Orthoptera, Ensifera and
      Caelifera. Anterograde filling and Golgi impregnation of maxillary receptor
      neurons revealed two patterns of innervation, the ensiferous and the caeliferous
      type. In both ensiferans and caeliferans, receptor neurons arborised within the
      tritocerebrum, the antennal motor- and mechano-sensory centre and the lobus
      glomerulatus. In ensiferans, additional areas of innervation were found in the
      lobus glomerulatus and in a previously undescribed neuropil, here referred to as
      the accessory lobus glomerulatus. In relation to the anatomical data a putative
      functional segregation of the neuropil into gustatory-, olfactory- and mechano
      sensory centres is implied.

PMID- 18088936
TI  - Serotonin-immunoreactive neurons in the ventral nerve cord of Crustacea: a
      character to study aspects of arthropod phylogeny.
AB  - The number of serotonin-expressing neurons in the nervous system of Euarthropoda
      is small and their neurites have a characteristic branching pattern. They can be
      identified individually, which provides a character well suited for phylogenetic
      analyses. In order to gain data that may be useful in the ongoing discussion on
      insect-crustacean relationships, we documented the pattern of serotonin
      immunoreactive neurons in the ventral nerve cord of four crustacean species: the
      phyllocarid malacostracan Nebalia bipes Fabricius, 1780 (Phyllocarida,
      Leptostraca) and the entomostracans Artemia salina Linnaeus, 1758 (Branchiopoda,
      Anostraca, Sarsostraca), Triops cancriformis Bosc, 1801 (Branchiopoda,
      Phyllopoda, Calmanostraca, Notostraca), and Leptestheria dahalacensis Ruppell,
      1837 (Branchiopoda, Phyllopoda, Diplostraca, Conchostraca, Spinicaudata). In the
      entomostracan taxa investigated, the pattern of serotonergic cells in the
      thoracic hemiganglia comprises an anterior and a posterior bilateral pair of
      neurons with ipsi- and/or contralateral neurites. Comparing these data to
      existing information on serotonin-immunoreactivity in the ventral nerve cord of
      other malacostracan and entomostracan groups enabled us to determine several
      features of these thoracic neurons being part of the ground pattern of these
      taxa. Our data demonstrate that studying individually identifiable neurons in
      Arthropoda can be used to analyse the phylogeny of this taxon.

PMID- 18088937
TI  - The elytra-to-body binding mechanism of the flightless rainforest species Tabarus
      montanus Kaszab (Coleoptera: Tenebrionidea).
AB  - The elytra-to-body binding mechanism of the flightless rainforest species Tabarus
      montanus Kaszab (Coleoptera: Tenebrionidea) is described. Previously, studies on
      this complex character system in tenebrionids have focused mostly on either fully
      winged or flightless, desert-dwelling species with a hermetically sealed
      subelytral cavity. Data presented here show that the rainforest species Ta.
      montanus has permanently joined interlocking macrostructures between the two
      elytra along the midline and between the elytral epipleuron and the sides of the
      body. These are very similar adaptations to ones found in flightless desert
      tenebrionids. Frictional patches of microtrichia, previously reported in all wing
      folding beetle suborders including flightless taxa, are completely absent in Ta.
      montanus. This constitutes the first report of the complete loss of frictional
      microtrichia patches in a beetle with fully-developed elytra. Sensory organs
      (hair sensilla), usually involved in the correct positioning of the elytra over
      the beetles' body at rest are also absent in Ta. montanus. The significance of
      these results relating to the evolution of the tenebrionid subelytral cavity is
      discussed.

PMID- 18088938
TI  - The architecture of the anterior appendage in the egg of the assassin bug, Zelus
      longipes (Hemiptera: Reduviidae).
AB  - The eggshell of Zelus longipes, a Hemiptera species of the family Reduviidae
      (assassin bugs), has been studied using Scanning Electron Microscopy (SEM). The
      emphasis was on the architecture of an anterior appendage connected to the main
      eggshell of both ovarian and deposited eggs. The analysis of eggs fractured at
      various angles and levels reveals a relatively complex organization of this
      appendage. There is a cylindrical outer layer, the veil, of roughly the same
      diameter as, and continuous with, the main eggshell. At its anterior pole, the
      veil folds inwards and forms an hourglass-shaped tube that is attached through
      slender extensions to a curved plate oriented at right angles to the long axis of
      the egg and spanning the internal diameter of the veil. The plate is solid at the
      center, shows honeycomb-shaped perforations in its mid-section and contains a
      very delicate meshwork along its circumference. Underneath the plate lies a
      hollow cylinder oriented at right angles to the long axis of the egg and attached
      to the anterior plate of the egg, the operculum. The outer openings of aeropyles
      lie at the inner face of the veil and at its base. While the outer surface of the
      entire eggshell appears smooth, the inner face of the anterior appendage is
      highly and diversely sculptured. The eggs are deposited in batches of at least 15
      and completely surrounded by viscous secretion. This substance does not encroach
      on the anterior appendage. The major function of this appendage may lie in the
      protection of the aeropyles and particularly in preventing their being clogged by
      the viscous material.

PMID- 18088939
TI  - Structural organization of the sex pheromone gland in Helicoverpa zea in relation
      to pheromone production and release.
AB  - Morphological location of the sex pheromone producing area in the ovipositor of
      the female corn earworm Helicoverpa zea, was correlated with gas chromatographic
      analysis of the extracted pheromone. Histological studies showed that the
      pheromone gland occupied an almost complete ring of specialized columnar cells
      between the 8th and 9th abdominal segments. Ultrastructure of the pheromone gland
      cells revealed distinct features such as microvilli, pockets of granular
      material, intercellular canals with abundant desmosomes. Apparent changes in some
      of these features are associated with phases of pheromone production and non
      production. Examination of the tissue with low temperature scanning electron
      microscopy showed the presence of excreted droplets at the tips of cuticular
      hairs in the glandular area during the period of pheromone production.

PMID- 18088940
TI  - The hinged back plate mechanism in glassy wax tests of New Zealand male soft
      scale insects (Hemiptera: Coccoidea: Coccidae).
AB  - Male scale insects (Hemiptera: Coccoidea) undergo a metamorphosis of the
      neometabola type, from scale-like nymph through prepupa and pupa to winged adult.
      The nymphal instar before prepupa secretes a waxy protective covering that
      remains in place throughout metamorphosis and these covers are characteristic of
      each family of scale insects. Most scale insect families (e.g. mealybugs,
      eriococcids, diaspidids) have rather loosely woven male covers, but male nymphs
      in the family Coccidae (soft scales) construct more rigid, glassy wax tests,
      which need a special mechanism for adult emergence. In the New Zealand male soft
      scales, a suture across the posterior quarter of the test enables the back plate
      to flex at a pair of hinges, to be raised up off the substrate, and so allow
      egress. The waxy back plate hinges are secreted by groups of tubular ducts on the
      abdominal dorsum of 2nd-instar males, during construction of the test. Scanning
      electron micrographs (SEMs) show the detail and diversity of hinge types. The wax
      tests of most New Zealand Coccidae, both female and male, are apparently unique
      in that they are constructed in rows of hexagonal plates, separated by sutures,
      however in the male test, the sutures are all fused except for the back plate
      suture. The two species in the endemic New Zealand genus Pounamococcus have male
      tests more like those of species in the Australian genus Austrolecanium.

PMID- 18088941
TI  - Comparative morphology and evolution of the funnel warts of larval Lymantriidae
      (Lepidoptera).
AB  - The larval funnel warts of 14 species of Lymantriidae (tussock moths) were
      investigated by means of scanning electron microscopy. The smaller, paired
      osmeteria on other abdominal segments were also inspected in four of the species.
      It seems that the bilaterally symmetrical funnel warts have developed by fusion
      of two smaller, single osmeteria. Based on the morphological findings from
      surface views and inside views of the structures, we made an attempt to
      reconstruct the pathway of evolution of the funnel warts. The high degree of
      specific modifications of the funnel warts appears valuable for analyses of the
      phylogenetic relationship of the investigated species.

PMID- 18088942
TI  - Larval anatomy and structure of absorbing epithelia in the aphid parasitoid
      Aphidius ervi Haliday (Hymenoptera, Braconidae).
AB  - The present work describes Aphidius ervi Haliday (Hymenoptera, Braconidae) larval
      anatomy and development, focusing on time-related changes of body structure and
      cell ultrastructure, especially of the epithelial layers involved in nutrient
      absorption. Newly hatched 1st instar larvae of A. ervi are characterised by gut
      absence and a compact cluster of cells makes up their body. As the parasitoid
      larva develops, the central undifferentiated cell mass becomes hollowed out,
      leading to the formation of gut anlage. This suggests that absorption of
      nutrients at that stage may take place through the body surface, as more directly
      demonstrated by the occurrence on the epidermis of proteins associated with
      transepithelial transport, such as Na(+)/K(+)-ATPase and alkaline phosphatase
      (ALP). Second instar larvae show the presence of the gut with a well
      differentiated brush border and a peritrophic membrane. Gut cells are filled by
      masses of glycogen granules and lipid droplets. The tracheal system starts to be
      visible. The haemocoel becomes evident in late 2nd instar, and contains large
      silk glands. Mature 3rd instar larvae are typically hymenopteriform. The midgut
      accounts for most of the body volume and is actively involved in nutrient
      absorption, as indicated by the well developed brush border and by the presence
      of Na(+)/K(+)-ATPase and ALP on the basolateral and luminal membrane
      respectively. At this stage, large lipid droplets have gradually replaced the
      cellular glycogen stores in the midgut cells. The tracheae are completely
      differentiated, but their internal lumen still contains fibrillar material,
      suggesting that they are not functional as long as host fluids bath the
      parasitoid larva. In late 3rd instar larvae, silk glands, structurally similar to
      Malpighian tubules, show a very intense vesicular traffic toward the internal
      lumen, which, eventually, results in being filled by secretion products,
      suggesting the possible recycling of metabolic waste products during mummy
      formation.

PMID- 18088943
TI  - Structural organization of the copulation site in the medfly Ceratitis capitata
      (Diptera: Tephritidae) and observations on sperm transfer and storage.
AB  - The copulation site of the medfly Ceratitis capitata was investigated at
      anatomical and ultrastructural levels. It consists of the anterior vagina, with a
      ventral fertilization chamber and a dorsal insemination pocket into which the two
      spermathecal ducts open. The fertilization chamber is an organ comprised of a
      number of alveoli that in virgin females are filled with a filamentous secretion,
      whereas in mated females contain sperm bundles. Through study of the internal
      morphology of the aedeagus, its position in the anterior vagina, and the direct
      observation of sperm transfer and storage, we confirmed that sperm are ejaculated
      through two gonopores at the top of the distiphallus and another at the base of
      the genital rod. The sperm flow dorsally into the insemination pocket and
      ventrally into the fertilization chamber. During copulation, the two spermathecae
      and the fertilization chamber are progressively filled with spermatozoa.

PMID- 18088944
TI  - Comparative spermatology in Plecoptera (Insecta): an ultrastructural
      investigation on four species.
AB  - The ultrastructure of spermatozoa of four Plecoptera species, Leuctra fusca
      Linnaeus, Brachyptera risi (Morton), Taeniopteryx stankovitchi Ikonomov, T.
      kuehtreiberi (Aubert), was investigated by light microscopy, scanning and
      transmission electron microscopy, and immunofluorescence microscopy. The
      spermatozoa of all the species have a complex acrosome, are filiform and
      flagellate, with a '9+9+2' axoneme flanked by two mitochondrial derivatives.
      However, the structure shows a certain interspecific heterogeneity. L. fusca has
      a short conical nucleus in the apical position and an axoneme flanked by two
      accessory bodies. In the sperm of the Taeniopterygidae, the nucleus is a long
      cylindrical body which lies between the two mitochondrial derivatives flanking
      the axoneme for most of its length. Our results suggest a close phylogenetic
      affinity between Plecoptera and the other orders of Polyneoptera, although the
      proposed sister-group relationship between Plecoptera and Embioptera cannot be
      confirmed.

PMID- 18088945
TI  - Formation and structure of egg capsules in scale insects (Hemiptera, Coccinea) I.
      Ortheziidae.
AB  - The paired ovaries of the investigated species are composed of 20-30 ovarioles of
      a telotrophic-meroistic type. Each ovariole is subdivided into an apical
      tropharium (=trophic chamber) and a vitellarium that contains a single developing
      oocyte. This oocyte is surrounded by a mono-layered follicular epithelium that is
      responsible for synthesis of precursors of egg envelopes. In Orthezia, synthesis
      and secretion of precursors of egg envelopes (=choriogenesis) and accumulation of
      reserve substances in the oocyte cytoplasm (=vitellogenesis) start at the same
      time. The egg capsule is composed of two envelopes: an internal, thick vitelline
      envelope and an external, very thin chorion. The egg surface is covered with
      numerous, irregularly arranged waxy filaments of spiral shape. Eggs are devoid of
      the micropylar, aeropylar and hydropylar openings.

PMID- 18088946
TI  - Molt-inhibiting hormone immunoreactive neurons in the eyestalk neuroendocrine
      system of the blue crab, Callinectes sapidus.
AB  - The production of ecdysteroid molting hormones by crustacean Y-organs is
      negatively regulated by a neuropeptide, molt-inhibiting hormone. It is generally
      agreed that molt-inhibiting hormone is produced and released by the eyestalk
      neuroendocrine system. In the present study, immunocytochemical methods were used
      to detect molt-inhibiting hormone immunoreactive neurons in eyestalk ganglia of
      the blue crab, Callinectes sapidus. The primary antiserum used was generated
      against molt-inhibiting hormone of the green shore crab, Carcinus maenas. A
      preliminary Western blot analysis indicated the antiserum binds molt-inhibiting
      hormone of Callinectes sapidus. Using confocal and conventional
      immunofluorescence microscopy, molt-inhibiting hormone immunoreactivity was
      visualized in whole mounts and thin sections of Callinectes sapidus eyestalk
      ganglia. Immunoreactivity was detected in 15-25 neurosecretory cell bodies in the
      medulla terminalis X-organ, their associated axons and collateral branches, and
      their axon terminals in the neurohemal sinus gland. The cellular organization of
      molt-inhibiting hormone immunoreactive neurons in blue crabs is generally similar
      to that reported for other crab species. The combined results suggest the
      cellular structure of the molt-inhibiting hormone neuroendocrine system is highly
      conserved among brachyurans.

PMID- 18088947
TI  - The predatory legs of Philonthus marginatus (Coleoptera, Staphylinidae):
      functional morphology and tarsal ultrastructure.
AB  - Representatives of the staphylinid beetle Philonthus marginatus are characterized
      by highly modified raptorial forelegs which are used to strike prey in a
      particularly fast manner. Beetles ready to capture prey remain in a
      characteristic precapture ambush posture characterized by lifted and folded
      forelegs. Triggered by sensory input from the antenna or other parts of the fore
      body, the actual strike is released, essentially taking the form of a rapid
      (about 9 ms) depression of the unfolding forelegs towards the prey. This movement
      is based on the presence of a coxo-trochanteral catch mechanism and a
      particularly wide angle of rotation in the coxo-trochanteral joint. It is made
      possible by the specific mechanics of this joint which probably also involves a
      co-contraction of the antagonistic trochantero-femoral flexor and extensor
      muscles suggesting a spring-loaded system. This phase of the strike is
      immediately followed by fixation of the prey by the ventral adhesive tarsal setae
      supported by a grasp of the flexing last tarsomere and the claws. After
      withdrawal of the forelegs together with the prey, the sequence eventually
      results in the formation of a capture-basket formed frontally by the
      perpendicularly flexing head and laterally by the spiny inner sides of the coxae.

PMID- 18088948
TI  - Morphology of a thermosensitive multipolar neuron in the infrared organ of
      Merimna atrata (Coleoptera, Buprestidae).
AB  - Two pairs of infrared (IR) organs are situated ventrolaterally on the second and
      third abdominal sternites of the Australian fire beetle Merimna atrata
      (Buprestidae). In ventral view, each IR organ has a round IR absorbing area under
      which a sensory complex is attached to the epidermis. The main component of the
      complex is a single large multipolar neuron and its mass of highly branched
      dendrites. All parts of this neuron are enveloped in glial cells. The proximal
      primary dendrites, which arise from the soma, finally branch into several hundred
      tightly packed terminal dendrites, which contain many mitochondria. We term this
      unusual morphology of the dendritic region a terminal dendritic mass (TDM).
      Additionally, two chordotonal organs were found in each sensory complex. Their
      somata are integrated in the complex and the dendrites extend to the periphery of
      the absorbing area. The bauplan of the dendritic region is reminiscent of the
      thermosensitive trigeminal nerve fibers innervating the absorbing structures in
      the IR receptors in boid and crotalid snakes. Because this multipolar neuron also
      functions as a thermoreceptor, another example of a functional analogy between
      insect and vertebrate sensory systems could be demonstrated.

PMID- 18088949
TI  - Physiological status and change of cytoplasmic lipid droplets in the pheromone
      producing cells of the silkmoth, Bombyx mori (Lepidoptera, Bombycidae).
AB  - Changes in size and number of cytoplasmic lipid droplets were quantified in the
      pheromone gland (PG) of Bombyx mori before and after adult eclosion. Two days
      before eclosion, size and number of droplets are small (diameter is 2-7 microm)
      and few. The formation and significant proliferation of larger droplets (5-12
      microm) take place between 2 days and 1 day before eclosion. From the day of
      emergence until day 3 a fluctuation in size and number of lipid droplets during
      the photophase (4h intervals) is observed. The changes are more characteristic
      and dramatic on the day of emergence and first day, while attenuation of these
      changes can be observed from the second day and seems to disappear by day 4.
      Bombykol content, at each respective time, is in good correlation with the
      observed fluctuation in lipid droplet parameters. Highest bombykol production
      daily is observed towards the early evening, when lipid droplets are the smallest
      (2-4 microm) and most numerous. By day 4, however, this regularity also ceases.
      In 24h old mated females PG cell structure is quite similar to newly emerged
      ones. In glands of 72 h old decapitated females the formation of 'extra' large
      lipid droplets is remarkable. In vivo pheromone biosynthesis activating
      neuropeptide (PBAN) treatment, however, induced the formation of many small
      droplets, although numerous larger ones also remained. The morphological changes
      in lipid droplets and cellular dynamics associated with the external signal of
      PBAN in the PG suggest a storage-pool function of the lipid droplets.

PMID- 18088950
TI  - F-actin is a component of the karyosome in neuropteran oocyte nuclei.
AB  - The principles underlying the assembly of intranuclear compartments are only
      beginning to be understood. The karyosome is an organelle typical of oocyte
      nuclei. It represents the tightly packed oocyte chromosomes, arrested at the
      diplotene of meiotic prophase. It has been known from several insect orders that
      a prominent capsule of unknown materials is built around the karyosome in the
      course of previtellogenesis and vitellogenesis. Here we show that F-actin,
      detected by dye-coupled phalloidin, is a major molecular component of the
      karyosome capsule in Neuroptera. We investigated capsule formation in six species
      belonging to the family Chrysopidae. Though F-actin was present in the capsules
      of all six species there were striking interspecific differences in the
      morphological array of actin filaments and the developmental dynamics of actin
      deposition in the capsule. The potential biological significance of the karyosome
      capsule is discussed with respect to the presence of extrachromosomal rDNA in
      neuropteran oocytes and the molecular functions known from F-actin. Our results
      corroborate the still controversial hypothesis of a role for actin as a nuclear
      protein.

PMID- 18088951
TI  - Ultrastructure and function of nurse cells in phthirapterans. Possible function
      of ramified nurse cell nuclei in the cytoplasm transfer.
AB  - The structure of nurse cells as well as the distribution of cytoskeletal elements
      (actin filaments, microtubules) in three representatives of phthirapterans: the
      pig louse, Haematopinus suis (Anoplura) and bird lice, Eomenacanthus stramineus,
      Columbicola columbae (Mallophaga) were investigated. All three species have
      polytrophic-meroistic ovaries which means that each oocyte remains connected with
      a group of nurse cells via specialized cytoplasmic canals-intercellular bridges
      (ring canals). Throughout vitellogenesis, various macromolecules as well as
      organelles (mitochondria, endoplasmic reticulum vesicles, ribosomes) are
      transferred from the nurse cells to the oocyte. During this flow, the nurse cell
      nuclei do not enter the oocyte and are retained in the cell centers. In
      holometabolous insects (e.g. Drosophila, hymenopterans), the central position of
      nurse cell nuclei is maintained by cytoskeletal elements (actin filaments or
      microtubules). In the investigated species, the nurse cells are equipped with
      large, highly extended (irregularly lobed) nuclei. The inner nuclear membrane is
      lined with a relatively thick layer of nuclear lamina. Ultrastructural analysis
      and staining with rhodamine-labeled phalloidin revealed that the nurse cell
      cytoskeleton is poorly developed and represented only by: (1) single microtubules
      in the perinuclear cytoplasm; and (2) the F-actin layer in the cortical
      cytoplasm. In the light of this, we postulate that in phthirapterans the position
      of nurse cell nuclei during the cytoplasm transfer is maintained not by the
      cytoskeletal elements, but by a largely extended shape of the nuclei (i.e. their
      elongated extensions).

PMID- 18088952
TI  - Transformations of epithelial monolayers during wing development of Manduca
      sexta.
AB  - The two epithelial monolayers of the insect wing undergo striking morphogenetic
      changes during the course of adult development, but the exact interactions
      between these monolayers were not evident until the ultrastructure of the cells
      was carefully examined. The interaction of the dorsal monolayer with the ventral
      monolayer continually changes as the two initially separate monolayers first lose
      their pupal basal laminae and then come together along a sharp interface to form
      microtubule-associated junctions. As blood space between the two monolayers
      expands 2 days later, new adult basal laminae and cuticle form. Concomitantly the
      epithelial cells stretch along their apicobasal axes to create a thin cellular M
      layer halfway between the dorsal and ventral surfaces of the wing that represents
      the site where connections between the monolayers are maintained at specialized
      basal junctions. The elongated processes of each monolayer that make up this M
      layer first fasciculate and then span the space separating the two monolayers,
      but only at relatively widely-spaced intervals. During later stages of adult
      development, dense aggregates of microtubules appear in these epithelial
      processes and presumably contract as cells dramatically shorten along their
      apicobasal axes during expansion of the wing. Examination of the ultrastructure
      of the developing adult wing has revealed how certain cellular events can account
      for the mechanics of cuticle and wing expansion after adult emergence.

PMID- 18088953
TI  - The endoskeletal structures in arthropods: cytology, morphology and evolution.
AB  - The paper proposes an overview of the endoskeletal structures of the head and
      trunk in the different arthropod groups: Chelicerata, Crustacea, Myriapoda and
      Hexapoda (=Insecta s.l.). Two major endoskeletal systems are reported with their
      cytological characteristics: those made up of connective tissue derived from
      muscular tendons, and those consisting of cuticular rods or plates arising from
      integumentary ingrowths. The morphological value of the various endoskeletal
      structures, their possible homologies in different groups, and their presumed
      evolutionary changes are discussed. This survey may be considered as a first step
      to use morphological characteristics of the endoskeleton in future cladistic
      analyses to assess the phylogeny of arthropods.

PMID- 18088954
TI  - Allometry and resolution of bee eyes (Apoidea).
AB  - A sample of compound eyes from 15 species of female pollen foraging bees (apiform
      Apoidea) was morphometrically analyzed. These species were chosen for size
      differences, different social organization, and a wide geographic and taxonomic
      distribution (Apidae, Megachilidae, Andrenidae, Halictidae). The results
      demonstrate the following characteristics for the typical compound eye in female
      foraging bees: (1) the vertical diameter of the eye is about twice the horizontal
      diameter; (2) the eyes of diurnal foragers scale isometrically with body size;
      (3) the eyes of three species of nocturnal foragers have about 1.8 times the
      surface area as compared to diurnal foragers of matching size; (4) the number of
      ommatidia per eye range from about 1000 in Perdita minima to about 16 000 in
      Xylocopa latipes; and (5) the corresponding mean interommatidial angles range
      from 4.7 to 1.2 degrees . Body size, rather than species-specific ecological
      adaptation, is the major (97%) determinant of the number of ommatidia per eye in
      diurnal, as well as nocturnal foragers. The number of ommatidia per eye, and
      hence the visual resolution, is proportional to the square root of both body size
      and eye size across all species studied. The eye parameter (the product of the
      mean interommatidial angle and the mean lens diameter) increases slightly with
      decreasing body size. All this is taken as evidence that the features of the
      bees' visual macro-niche remained largely constant over the roughly 130 million
      years of their macro-evolution.

PMID- 18088955
TI  - Ultrastructural characterization of antennal sensilla and immunocytochemical
      localization of a chemosensory protein in Carausius morosus Brunner (Phasmida:
      Phasmatidae).
AB  - The aim of this work was to investigate the olfactory system of the walking stick
      insect, Carausius morosus. Morphological, ultrastructural and immunocytochemical
      studies of adult female antennae were conducted by scanning and transmission
      electron microscopy. Extensive cross-section series were made through the last
      antennal segment to define the cuticular apparatus, wall pore distribution and
      the number of innervating receptor neurons of each sensillum type. Single-walled
      wall pore sensilla occur in three subtypes: (i) with 27 or 28 branched receptor
      neurons, (ii) with two branched neurons and (iii) with one or two unbranched
      neurons, respectively. Double-walled wall pore sensilla were found in two
      subtypes with spoke channels, one with four unbranched neurons, the other with
      two unbranched neurons. One terminal pore sensillum was found, showing two
      cavities within the hair and being innervated by six sensory cells.
      Immunocytochemical experiments were performed to show the localization of a 19
      kDa soluble protein found in the chemosensory organs of C. morosus. This protein
      shows an amino acid sequence homologous to the family of chemosensory proteins
      (CSP). The polyclonal antibody raised against the purified protein (CSP-cmA)
      showed, for the first time in CSPs, a strong labeling in olfactory sensilla,
      specifically in the sensillum lymph surrounding the dendritic branches of SW-WP
      sensilla and in the uninnervated lumen between the two concentric walls of DW-WP
      type 1 sensilla.

PMID- 18088956
TI  - A single cell analysis of engrailed expression in the early embryonic brain of
      the grasshopper Schistocerca gregaria: ontogeny and identity of the secondary
      headspot cells.
AB  - The expression pattern of the segment polarity gene engrailed was studied at the
      single cell level in the protocerebrum of the early embryonic brain of the
      grasshopper Schistocerca gregaria, the neuromere containing the secondary
      headspot cells. The engrailed protein is first expressed in the protocerebrum at
      about 22% of embryogenesis by a group of identified neuroblasts bordering the
      antennal lobe. The number of immunoreactive neuroblasts increases up to 26% of
      embryogenesis and then rapidly declines so that by 30% only the three most
      posterior remain immunoreactive. These three neuroblasts become incorporated into
      the developing antennal lobe of the deutocerebrum. Subsequently, there is a
      progressive re-expression of the engrailed protein in the protocerebrum by the so
      called six secondary headspot cells. These are the first born sibling progeny of
      three identified protocerebral neuroblasts which themselves expressed the
      engrailed protein prior to generating their lineages, and so represents a
      reacquisition of engrailed expression within identified clones. The secondary
      headspot cells are neurons which direct axonal processes into the developing
      optic tract and so contribute to the primary axon scaffold of the brain. From our
      analysis of their ontogeny, we conclude that the secondary headspot cells do not
      represent a segmental border in the brain.

PMID- 18088957
TI  - Ultrastructure of male sex pheromone glands in abdominal tergites of five
      Lutzomyia sandfly species (Diptera: Psychodidae).
AB  - The fine structure of male sex pheromone disseminating structures on abdominal
      segments of five species of Lutzomyia sandflies (Diptera: Psychodidae) was
      analyzed. Scanning electron microscopy showed that in Lutzomyia cruzi [Mem. Inst.
      Oswaldo Cruz 33 (1938) 349] and Lutzomyia longipalpis [Mem. Inst. Oswaldo Cruz 4
      (1912) 84], the disseminating structures are located in pale spots on abdominal
      tergites IV or III and IV and are morphologically similar, appearing as small
      round cuticular elevations with a central pore. Observation of abdominal tergites
      of L. longipalpis pupae showed that the spots, but not the structures, are
      already present in this stage. In Lutzomyia lenti [Mem. Inst. Oswaldo Cruz 33
      (1938) 349] and Lutzomyia carmelinoi [Mem. Inst. Oswaldo Cruz 81 (1986) 323]
      adult males, the disseminating structures are present on tergal segments V and
      VI, where pale spots could not be observed, and appear as apple-like elevations
      with a central pore. In Lutzomyia renei, a single disseminating structure is
      found at the anterior region of tergal segment VI. Transmission electron
      microscopy was used to analyze the gland cell fine structure in L. cruzi. Several
      class III gland cells are located side by side in the fourth abdominal segment.
      Each epidermal secretory cell contains a small reservoir and a short outlet
      channel through the cuticle.

PMID- 18088958
TI  - Morphometric analysis of the tracheal walls of the harvestmen Nemastoma lugubre
      (Arachnida, Opiliones, Nemastomatidae).
AB  - The tracheal system of harvestmen consists of two stem tracheae, which give rise
      to higher order tracheae that supply the extremities and internal organs. In this
      study, we used stereological morphometric methods to investigate diffusing
      capacities of the walls ('lateral diffusing capacity') of the tracheae of adult
      males and females of Nemastoma lugubre. Diffusing barriers of the tracheal walls
      tend to be thinnest (0.17-0.19 microm) for the smallest tracheae (inner diameter
      0.5-2 microm). In other tracheal classes the diffusing barriers increase with
      increasing diameters. Calculation of the mass-specific diffusing capacity for
      oxygen (D(O2)) of the walls of all higher order tracheae revealed 10.57 microl
      min(-1)g(-1)kPa(-1) for the females (mean body mass 3.8 mg) and 25.23 microl min(
      1)g(-1)kPa(-1) for the males (mean body mass 1.4 mg). In both animal groups, the
      main D(O2) (58-67%) lies in the tracheae with an inner diameter of 0.5-2 microm,
      but also tracheae up to an inner diameter of 20 microm allow gas exchange via the
      tracheal walls. Stem tracheae are of no importance for lateral diffusion. Our
      results are consistent with the hypothesis that the functional morphology of the
      tracheal system of harvestmen represents an 'intermediate state' between the
      tracheal system of insects in which gas exchange is focused on the distal
      portions and that of spiders, in which the walls of all tracheae serve in gas
      exchange.

PMID- 18088959
TI  - Vitellin polypeptide pathways in late insect yolk sacs.
AB  - A panel of monoclonal antibodies was raised against late yolk sacs of the stick
      insect Carausius morosus and tested by immunoblotting to establish the extent
      vitellin polypeptides are processed proteolytically during embryonic development.
      Cryosections of late yolk sacs were also examined by confocal laser microscopy to
      determine how vitellin cleavage products become spatially distributed amongst
      yolk granules during the same developmental period. Distinct labelling patterns
      were obtained on yolk granules depending on: (1) the nature of the proteolytic
      processing; (2) the origin of vitellin cleavage products; and ultimately (3)
      their molecular sizes. Monoclonal antibodies raised against vitellin cleavage
      products resulting from proteolytic processing appeared to label: (1) the entire
      volume of many yolk granules; (2) their limiting membrane; or (3) a number of
      small vesicles interposed between larger yolk granules. On the other hand,
      monoclonal antibodies against vitellin cleavage products that remain invariant
      throughout development appeared to label either the serosa membrane or the
      cytosolic space comprised between adjacent yolk granules. Data are interpreted as
      indicating that vitellin cleavage products may leak out from the yolk granules,
      gain access to the cytosolic space of the vitellophages and eventually percolate
      through the serosa membrane enclosing the yolk sac.

PMID- 18088960
TI  - An immunohistochemical study of structure and development of the nervous system
      in the brine shrimp Artemia salina Linnaeus, 1758 (Branchiopoda, Anostraca) with
      remarks on the evolution of the arthropod brain.
AB  - Brain morphology is an important character in the discussion of arthropod
      relationships. While a large body of literature is available on the brains of
      Hexapoda and Malacostraca, the structure of the brain has been rarely studied in
      representatives of the Entomostraca. This account examines the morphology and
      development of the nervous system in the brine shrimp Artemia salina Linnaeus,
      1758 (Crustacea, Branchiopoda, Anostraca) by classical histology and
      immunohistochemistry against synaptic proteins (synapsins), and the
      neurotransmitters serotonin and histamine. The results indicate that the shape of
      the developing larval brain in A. salina (a circumstomodeal ring of neuropil)
      closely resembles that in malacostracan embryos. Furthermore, the organization of
      the central complex as well as the tritocerebral innervation pattern of the
      labrum is homologous in this species and in Malacostraca. Nevertheless,
      differences exist in the layout of the deutocerebrum, specifically in the absence
      of olfactory glomeruli in A. salina while the glomerular organization of the
      olfactory lobe is a character in the ground pattern of Malacostraca. These
      findings are compared to the brain structure in other Euarthropoda and possible
      phylogenetic implications are discussed.

PMID- 18088961
TI  - Ultrastructure and orientation of ommatidia in the dorsal rim area of the locust
      compound eye.
AB  - In many insect species, a dorsal rim area (DRA) in the compound eye is adapted to
      analyze the sky polarization pattern for compass orientation. In the desert
      locust Schistocerca gregaria, these specializations are particularly striking.
      The DRA of the locust consists of about 400 ommatidia. The facets have an
      irregular shape, and pore canals are often present in the corneae. Screening
      pigment is missing in the region of the dioptric apparatus suggesting large
      receptive fields. The rhabdoms are shorter, but about four times larger in cross
      section than the rhabdoms of ordinary ommatida. Eight retinula cells contribute
      to the rhabdom. The microvilli of retinula cell 7 and of cells 1, 2, 5, 6, 8 are
      highly aligned throughout the rhabdom and form two blocks of orthogonal
      orientation. The microvilli in the minute rhabdomeres of retinula cells 3 and 4,
      in contrast, show no particular alignment. As in other insect species,
      microvillar orientations are arranged in a fan-like pattern across the DRA.
      Photoreceptor axons project to distinct areas in the dorsal lamina and medulla.
      The morphological specializations in the DRA of the locust eye most likely
      maximize the polarization sensitivity and suggest that the locust uses this eye
      region for analysis of the sky polarization pattern.

PMID- 18088962
TI  - Segmental specializations in the Malpighian tubules of the fire ant Solenopsis
      saevissima Forel 1904 (Myrmicinae): an electron microscopical study.
AB  - The Malpighian tubules of workers of the fire ant Solenopsis saevissima
      (Myrmicinae) were analyzed by scanning and transmission electron microscopy in
      order to determine their functional organization and association with the hindgut
      epithelium. The ants showed six Malpighian tubules with three segments
      morphologically and structurally different. The proximal segment was long and its
      cells showed abundant smooth endoplasmic reticulum and lipid droplets, which
      suggest their role in lipid secretion. The mid segment was long and undulated and
      it was composed by the cells that showed the typical features of ion transporting
      epithelia. The distal segment, short and flattened, adheres to the rectum wall.
      The cells of this segment showed the basal lamina fused to that of the rectum, it
      is probable that this part of the tubule may play a role in ion and water uptake
      from the feces.

PMID- 18088963
TI  - A light and electron microscopical study of the spermathecae and ventral
      receptacle of Anastrepha suspensa (Diptera: Tephritidae) and implications in
      female influence of sperm storage.
AB  - Female insects with multiple sperm storage organs may potentially influence
      patterns of paternity by differential storage of sperm from competing males. The
      Caribbean Fruit Fly, Anastrepha suspensa, stores sperm differentially with
      respect to its three spermathecae. To understand the mechanisms and processes
      responsible for patterns of sperm storage and use in A. suspensa, details of the
      fine structure of female sperm storage organs were resolved by UV-light
      microscopy, confocal microscopy, tissue sectioning, and scanning and transmission
      electron microscopy. Structures not previously described for this species include
      a ventral receptacle for sperm storage and osmoregulation, a conical-shaped valve
      at the junction between the spermathecal capsules and their ducts, laminar and
      granular secretions, secretions from the signum, hemocytes surrounding the
      spermathecae, and spermathecae with sclerotized, hollow projections that
      terminate in single glandular cells. The independent organization of sperm
      storage organs, spermathecal ducts, associated musculature, gland cells, and
      innervation offer possible mechanisms by which sperm movement may be influenced
      by females. The implications of these structures for insemination and
      fertilization events are discussed.

PMID- 18088964
TI  - Ultrastructural investigations of testes and spermiogenesis in two species of
      halacarid mites (Halacaridae, Actinedida, Actinotrichida): Thalassarachna basteri
      from the Baltic Sea and Halacarellus thomasi from McMurdo Sound (Antarctica).
AB  - Testes and sperm cells of two species of halacarid mites, Thalassarachna basteri
      from the Baltic Sea and Halacarellus thomasi from McMurdo Sound (Antarctica),
      were investigated. Testes are paired structures, composed of a glandular and a
      germinal part. The testicular lumen is filled with a very complex secretion that
      contributes to sperm cell aggregates. Early spermatids of T. basteri display
      unusual chromatin condensation within the nucleus, but the formation of an
      acrosomal complex with a small acrosomal vesicle and a long acrosomal filament
      can be regarded as typical for the group. Tubular invaginations of the
      plasmalemma occur at the cell periphery. A deep, ring-like infold divides the
      cell into one part containing the chromatin body and another containing mainly
      the invaginations and the acrosomal complex. The mature sperm cell is ovoid,
      aflagellate and surrounded by a distinct secretion sheath. In H. thomasi only a
      limited number of spermiogenesis stages were observable. Chromatin condensation
      was rather similar and peripheral invaginations also occurred. However, no
      acrosomal complex was observed in the early stages. The division of the mature
      sperm cells into two halves was even more pronounced in H. thomasi, since one
      half of the cell contained masses of convoluted structures. The same half also
      contained a structure that remotely resembled an acrosomal complex. The observed
      differences between T. basteri and H. thomasi sperms support the placing of the
      two halacarids in separate genera.

PMID- 18088965
TI  - The foregut-ossicle system of Dromia wilsoni, Dromia personata and Lauridromia
      intermedia (Decapoda, Brachyura, Dromiidae), studied with a new staining method.
AB  - The ossicles of the cardiac and pyloric foregut of three species of decapods:
      Dromia wilsoni [Fulton and Grant, 1902], Dromia personata [Linne, 1758] and
      Lauridromia intermedia [Lauri, 1906] are described and illustrated in detail.
      Five new ossicles are recognized based on a specific staining-method with
      Alizarin-Red. The ossicle terminology of the brachyuran foregut is revised now to
      include 37 ossicles. All described ossicles are documented by drawings and
      photographs. The two new cardiac ossicles, the prepterocardiac and the
      postpterocardiac ossicles are narrow ossicles associated with the pterocardiac
      ossicles at the antero-dorsal margin of the cardiac foregut. The pyloric foregut
      includes the newly described lateral mesopyloric- and the posterior uropyloric
      ossicles. These pyloric ossicles are clearly recognizable only in the stained
      condition. Based on our data we provide new additional evidence for brachyuran
      monophyly and the paraphyletic status of the podotrematan crabs.

PMID- 18088966
TI  - Fine structure of antennal sensilla basiconica and their detection of plant
      volatiles in the eucalyptus woodborer, Phoracantha semipunctata Fabricius
      (Coleoptera: Cerambycidae).
AB  - The ultrastructure and distribution pattern of two types of basiconic sensilla (I
      and II) on the antennal flagellum of both sexes of Phoracantha semipunctata
      (Coleoptera: Cerambycidae) was investigated by scanning and transmission electron
      microscope. Both types are thin-walled multiporous sensilla and occur mostly
      along the anterior border of the Fl1-Fl6 flagellomeres, while on the distal
      flagellomeres (Fl7-Fl9) they are more evenly distributed on both surfaces.
      Clusters of sensilla basiconica II are found on the distal half of the anterior
      border of the Fl1-Fl6 flagellomeres. Sensilla basiconica I have one bipolar
      sensory cell with a branched distal dendrite, whereas the sensilla basiconica II
      contain two bipolar sensory cells with branched distal dendrites. No sexual
      dimorphism was found in the fine structure and distribution pattern of both types
      of sensilla basiconica. Responses from single sensory cells to host and non-host
      plant odors were examined, using gas chromatography linked with
      electrophysiological recordings. Most cells associated with each sensillum type
      were narrowly tuned, each specialized for the detection of one or two chemically
      related compounds. No clear functional distinction between the two morphological
      types of sensilla was found, although the few cells that responded specifically
      to non-host volatiles were associated with sensilla basiconica II.

PMID- 18088967
TI  - Ultrastructure of the excretory duct in the silk gland of the sugarcane borer
      Diatraea saccharalis (Lepidoptera: Pyralidae).
AB  - The excretory duct in the silk gland of the sugarcane borer Diatraea saccharalis
      consists of two morphologically distinct regions, recognized by scanning and
      transmission electron microscopy. The thin posterior region, adjacent to the
      glandular region, presents a regular surface. Secretory vesicles containing
      either electron-dense or fibrillar cuticular-like materials are observed in their
      apical cytoplasm; the same cuticular materials were detected as extracellular
      deposits among the microvilli. The short anterior region, near the common duct,
      exhibits surface protrusions; there are no secretory vesicles in their apical
      cytoplasm. These results show that only the duct cells at the posterior region
      are involved in the secretion of the cuticular intima elements. Desmosome-like
      structures were visualized linking together adjacent microvillar membranes only
      in the cells of anterior duct region, with unknown function. The transition
      between the duct and the glandular region is abrupt; the cells of the glandular
      and posterior duct regions present large amounts of microtubules. Nerve fibers
      can be observed between the duct cells in their two regions, suggesting that
      control of silk secretion may occur in the excretory duct via neurotransmitter
      liberation.

PMID- 18088968
TI  - Extrachromosomal rDNA amplification in the oocytes of Polystoechotes punctatus
      (Fabricius) (Insecta-Neuroptera-Polystoechotidae).
AB  - The ovary of Polystoechotes punctatus consists of several ovarioles of meroistic
      polytrophic type. Histological, histochemical and ultrastructural studies
      revealed that the extrachromosomal amplification of rDNA takes place in the
      oocyte nucleus. Prior to previtellogenic growth the oocyte nucleus contains the
      chromosomes of meiotic prophase and a condensed extra DNA body. Initial split of
      extrachromosomal DNA material into several fragments coincides with the
      appearance of a spherical, fine granular body (referred to as primary nucleolus).
      Its gradual fragmentation accompanied by further dispersion of amplified DNA
      results in the formation of a growing number of multiple nucleoli. Until mid
      previtellogenesis each multiple nucleolus contains detectable amount of rDNA. In
      the advanced stages of previtellogenesis rDNA can hardly be visualized within the
      multiple nucleoli, while chromosomes form a few dense aggregates randomly
      disposed in the karyoplasm. At the onset of vitellogenesis the chromosomes
      assemble to form a karyosome. In its close vicinity DNA-positive material
      reaggregates. Multiple nucleoli are either found on the periphery of this
      aggregation or merge within it. At the final stages of vitellogenesis the number
      of multiple nucleoli significantly decreases.

PMID- 18088969
TI  - Development of the mesendoderm in the dendrobranchiate shrimp Sicyonia ingentis.
AB  - Dendrobranchiate shrimp embryos form a 4-cell stage that resembles spiralians in
      its cell contacts, but cleavage proceeds radially without any further evidence of
      spiralian character. The fates of Sicyonia ingentis mesendoblasts were followed
      by nuclear staining and confocal microscopy. The dorsal mesendoblast produced
      yolk-endoderm, which proliferated from the anterior of the embryo to cover the
      dorsal interior. The ventral mesendoblast divided into the primordial endoblast
      and a cell that further divided into the primordial mesoteloblast and the
      primordial germ cell. The primordial endoblast divided into left and right
      endoblasts, which then underwent two teloblastic divisions, leaving behind two
      pairs of smaller descendants and the larger endoblasts at the dorsal posterior.
      The endoblasts then paused in cell division while extensive morphogenesis
      occurred in the ectoderm to form the naupliar segments. Ectoteloblasts formed at
      the posterior. The primordial mesoteloblast underwent two asymmetric divisions,
      synchronously with the endoblasts, to form two small descendants and M2 at the
      ventral posterior. From 15 to 18h, M2 divided laterally then dorsal-ventrally to
      form four descendants. The results extend the cell lineage of S. ingentis from
      the egg to the nauplius larva, and demonstrate that endoderm forms dorsal to
      teloblastic mesoderm from an early stage.

PMID- 18088970
TI  - Ovarian tumor expression is dependent on the functions of the somatic sex
      regulatory genes transformer-2 and doublesex.
AB  - The doublesex-dependent sex regulatory pathway in Drosophila controls major
      aspects of somatic sexual differentiation, but its expression is not required in
      the X/X germline. Nevertheless, mutations in doublesex and in the genes that
      directly regulate its expression, transformer and transformer-2, disrupt early
      stages of oogenic differentiation to produce gonads containing immature germ
      cells. This indicates a critical, but uncharacterized, set of soma-germline
      interactions essential for oogenesis. In this paper, we examined the effects of
      mutations in transformer-2 on the expression and function of the germline
      specific ovarian tumor gene. We demonstrated that in transformer-2 mutants, there
      was a marked reduction in the activity of the ovarian tumor promoter in the
      mutant germline. In addition, the phenotypic effects on the arrested germline
      could be partially suppressed by the simultaneous over-expression of both ovarian
      tumor and a second germline gene, Sex-lethal. This differs from transformer
      mutations, in which the over-expression of ovarian tumor alone is sufficient for
      a similar improvement in germline differentiation. In contrast to transformer-2,
      doublesex activity was not required for ovarian tumor promoter activity and we
      found indirect evidence that the doublesex male-specific function might have a
      negative regulatory effect. These data indicate that the components of the
      genetic pathway regulating somatic sexual differentiation have specific and
      differential effects on germline gene activity.

PMID- 18088971
TI  - Morphological and molecular data argue for the labrum being non-apical,
      articulated, and the appendage of the intercalary segment in the locust.
AB  - Our analysis of head segmentation in the locust embryo reveals that the labrum is
      not apical as often interpreted but constitutes the topologically fused
      appendicular pair of appendages of the third head metamere. Using molecular,
      immunocytochemical and retrograde axonal staining methods we show that this
      metamere, the intercalary segment, is innervated by the third brain neuromere-the
      tritocerebrum. Evidence for the appendicular nature of the labrum is firstly, the
      presence of an engrailed stripe within its posterior epithelium as is typical of
      all appendages in the early embryo. Secondly, the labrum is innervated by a
      segmental nerve originating from the third brain neuromere (the tritocerebrum).
      Immunocytochemical staining with Lazarillo and horseradish peroxidase antibodies
      reveal that sensory neurons on the labrum contribute to the segmental
      (tritocerebral) nerve via the labral nerve in the same way as for the appendages
      immediately anterior (antenna) and posterior (mandible) on the head. All but one
      of the adult and embryonic motoneurons innervating the muscles of the labrum have
      their cell bodies and dendrites located completely within the tritocerebral
      neuromere and putatively derive from engrailed expressing tritocerebral
      neuroblasts. Molecular evidence (repo) suggests the labrum is not only
      appendicular but also articulated, comprising two jointed elements homologous to
      the coxa and trochanter of the leg.

PMID- 18088972
TI  - Common design in a unique midline neuropil in the brains of arthropods.
AB  - Most insects possess an assemblage of midline neuropils in their protocerebrum
      called the central complex. Recent studies have identified comparable assemblages
      in the malacostracan protocerebrum. Studies of Drosophila melanogaster locomotory
      mutants suggest that in insects one role for the central complex might be to
      orchestrate limb actions. This is anecdotally supported by comparisons amongst
      insects suggesting that elaboration of central complex architecture correlates
      with complexity of limb motor repertoires. The present account describes
      immunocytochemical and neuroanatomical observations that reveal common design
      principles amongst midline neuropils in four arthropod clades, the hexapods,
      crustaceans, chilopods, and chelicerates and the absence of midline neuropils in
      diplopods. The chilopod midline neuropil, which is columnar and stratified and
      lacks chiasmal axons to the dorsal protocerebrum or connections to discrete
      satellite regions, may represent the plesiomorphous condition. The complete
      absence of a midline neuropil in diplopods supports previous neuroanatomical
      studies suggesting that the 'Myriapoda' are an artificial paraphyletic group. The
      columnar and layered arcuate midline neuropils of chelicerates are compared with
      columnar and layered midline neuropils of chilopods. No midline neuropil has been
      identified in a lophotrochozoan outgroup, the Polychaeta.

PMID- 18088973
TI  - Changes in the structure of the cuticle of Ixodes ricinus L. 1758 (Acari,
      Ixodidae) during feeding.
AB  - Female Ixodes ricinus (ticks) are able to consume several times as much as their
      own weight in food. The body volume increases without the animal moulting.
      Special structural and material characteristics of the cuticular exoskeleton
      render this phenomenon possible. Only the alloscutum, which has a very pronounced
      lamellar structure, extends. The individual lamellae correspond to surface folds
      in the outer endocuticle and the epicuticle covering it. The degree of folding is
      correlated to the nutritional state of the animal, which can be differentiated
      into three significant phases. The phase-dependent morphology of the surface
      structure and the cuticular layers of the alloscutum are described qualitatively
      and quantitatively in this paper. Furthermore, the presence of systematic
      deposits of resilin in the alloscutum, which are significant for the flexibility,
      is demonstrated.

PMID- 18088974
TI  - Evolution of the suctorial proboscis in pollen wasps (Masarinae, Vespidae).
AB  - The morphology and functional anatomy of the mouthparts of pollen wasps
      (Masarinae, Hymenoptera) are examined by dissection, light microscopy and
      scanning electron microscopy, supplemented by field observations of flower
      visiting behavior. This paper focuses on the evolution of the long suctorial
      proboscis in pollen wasps, which is formed by the glossa, in context with nectar
      feeding from narrow and deep corolla of flowers. Morphological innovations are
      described for flower visiting insects, in particular for Masarinae, that are
      crucial for the production of a long proboscis such as the formation of a closed,
      air-tight food tube, specializations in the apical intake region, modification of
      the basal articulation of the glossa, and novel means of retraction, extension
      and storage of the elongated parts. A cladistic analysis provides a framework to
      reconstruct the general pathways of proboscis evolution in pollen wasps. The
      elongation of the proboscis in context with nectar and pollen feeding is
      discussed for aculeate Hymenoptera.

PMID- 18088975
TI  - Hagen's glands of the parasitic wasp Diachasmimorpha longicaudata (Hymenoptera:
      Braconidae): ultrastructure and the detection of entomopoxvirus and parasitism
      specific proteins.
AB  - Hagen's glands of males of the parasitic wasp Diachasmimorpha longicaudata
      (Hymenoptera: Braconidae) secrete compounds that are involved in courtship and
      defense. Like the poison glands of female wasps, the Hagen's glands are
      secretory, membranous, and of ectodermal origin. The poison glands contain the
      symbiotic entomopoxvirus, DlEPV and the parasitism-specific protein, PSP 24.
      DlEPV proteins were detected in homogenates of male wasps. Our goal was to
      describe the ultrastructure of the Hagen's glands and determine whether they
      contain DlEPV virions and/or proteins as well as PSP 24. The Hagen's glands are
      bilateral and each consists of 12-16 tubules arranged in two clusters. In cross
      section, a tubule has three zones that enclose a central cuticle-lined lumen. The
      outermost zone consists of aggregates ('islands') of small vesicles,
      interconnected by narrow ductules that lead to large cuticle-lined ducts, which
      transport electron-dense material to the lumen prior to its release from the
      gland. Large vesicles in Zone 2 and a thick layer of ribosomes and rough
      endoplasmic reticula in Zone 3 are the likely sites of storage and protein
      synthesis, respectively. While DlEPV virions were not seen in the Hagen's gland,
      DlEPV and PSP 24 proteins were present.

PMID- 18088976
TI  - Morphology and formation of the eggshell in the tarnished plant bug, Lygus
      lineloaris (Palisot de Beauvois) (Hemiptera: Miridae).
AB  - Scanning and transmission electron microscopy were used to study the morphology
      and formation of the eggshell in the tarnished plant bug, Lygus lineolaris. Eggs
      are bean-shaped, with an operculum at the anterior end surrounded by a row of 36
      40 respiratory horns. Three micropylar openings are on the operculum, and are
      sealed in oviposited eggs. The chorion consists of the chorion proper and the
      innermost chorionic layer. An air layer composed of colonnades is present in the
      chorion. The innermost chorionic layer is homogeneous and electron lucent. The
      follicle cells secrete electron dense materials that later coalesced into the
      reticulated vitelline membrane. This is followed by the deposition of the
      innermost chorionic layer by the follicle cells. After the primordial innermost
      chorionic layer is formed, follicle cells at the anterior pole of the oocyte
      secrete the scaffold for the colonnades in the air layer. Later, the primordial
      scaffold matrix is redistributed and localized at the lateral and posterior end
      of the oocyte where it becomes secondarily modified. At the end of choriogenesis,
      follicle cells at the anterior pole secrete the operculum and respiratory horns.

PMID- 18088977
TI  - Comparative spermatology in Plecoptera (Insecta). II. An ultrastructural
      investigation on four species of Systellognatha.
AB  - Sperm structure of four Systellognatha species, Dinocras cephalotes (Curtis,
      1827) and Perla grandis (Rambur, 1841), family Perlidae, Siphonoperla torrentium
      (Pictet, 1841), family Chloroperlidae, and Isoperla grammatica (Poda, 1761),
      family Perlodidae, was investigated by light microscopy, scanning and
      transmission electron microscopy, and immunofluorescence microscopy. The
      spermatozoa of all the species are filiform and flagellate; they have an
      elongated compact nucleus, topped by either a bi-layered or three-layered
      acrosomal complex, and a '9+9+2' axoneme flanked by two mitochondrial
      derivatives. However, some variations have been observed, particularly regarding
      the morphology of the acrosomal complex, the shape of the nucleus, two more or
      less evident accessory bodies flanking the axoneme and the degree of
      crystallisation of the mitochondrial derivatives. Our results support the
      suggestion that Systellognatha is a monophyletic group, showing a single sperm
      pattern. Chloroperlidae and Perlodidae retain the plesiomorphic condition of some
      sperm characters while Perlidae show some autoapomorphies. A phylogenetic
      affinity between Plecoptera and the other orders of Polyneoptera has been
      confirmed.

PMID- 18088978
TI  - Morphology of the minute larva of Ptinella tenella, with special reference to
      effects of miniaturisation and the systematic position of Ptiliidae (Coleoptera:
      Staphylinoidea).
AB  - External and internal features of minute reared ex ovo larvae of Ptinella tenella
      Erichson with the head widths ranging from 108 to 138mum are described. In total
      139 setae (trichoid sensilla), 18 pores (non-trichoid sensilla), and 60 muscles
      were identified. The complexity of the chaetotaxy, the musculature of the head,
      the tentorium, and the digestive tract are not affected by the extremely small
      size of the larvae. Specific features, which may have resulted from
      miniaturisation are the elongate shape of the brain reaching the mesothorax
      posteriorly, the reduced condition of the thoracic sclerites and endosternites,
      the simplified musculature of the thorax and abdomen, and the loss of the
      abdominal spiracles. The monophyly of Ptiliidae is supported by the absence of
      head sutures, the presence of a setiferous protuberance close to the mandibular
      base, and the absence of a lacinia. Absence of abdominal spiracles and complete
      absence of eyes suggest the monophyly of a ptiliid subgroup which does not
      comprise Nossidium. Presence of a fimbriate galea is shared by larvae of
      Agyrtidae, Leiodidae, Ptiliidae, and Hydraenidae. The presence of a complex
      apical appendage on the distal maxillary palpomere and of hooks on abdominal
      segment X are possible synapomorphies of Ptiliidae and Hydraenidae. A description
      of the rearing procedure is provided and comments on feeding habits are made.

PMID- 18088979
TI  - Morphology and ultrastructure of paired prototergal glands in the adult rove
      beetle Philonthus varians (Coleoptera, Staphylinidae).
AB  - Philonthus and other genera of Philonthina possess a pair of prototergal glands
      located in the first abdominal tergum and hidden at rest by hind wings and
      elytra. In Philonthus varians they occupy the whole length of the tergum and form
      a pouch-like invaginated reservoir with a scaly glandular zone and a smooth
      outlet. A grille of long setae covers the opening of each gland. The fine
      structure of these glands is given for the first time. Three types of cells are
      found in the glandular epithelium. Epidermal cells underlie the cuticular scales,
      numerous class 1 secretory cells open in the centre of calyces made of finger
      like processes of the cuticle, and class 3 cells are connected to pored
      tubercles. A cytological comparison is made with the diverse class 1 cells
      described to date in Coleoptera. In these cells different evolutionary trends are
      shown in the structure of the cuticular apparatus, particularly in the number,
      size and position of the cuticular apertures as well as in the length and
      abundance of epicuticular filaments. A possible defensive function of the
      prototergal glands against pathogens and their interest for the phylogenetic
      study of Staphylininae are discussed.

PMID- 18088980
TI  - Evolution of the arthropod neuromuscular system. 1. Arrangement of muscles and
      innervation in the walking legs of a scorpion: Vaejovis spinigerus (Wood, 1863)
      Vaejovidae, Scorpiones, Arachnida.
AB  - (1) The musculature of the walking legs is analysed with regard to both
      morphology and function in the scorpion, Vaejovis spinigerus (Wood, 1863)
      (Vaejovidae, Scorpiones, Arachnida), and selected other species. Conspicuous
      features are multipartite muscles, muscles spanning two joints, and partial lack
      of antagonistic muscles. The muscle arrangement is compared to that in the
      walking limbs of other Arthropoda and possible phylogenetic implications are
      discussed. (2). Histochemical characterisation of selected leg muscles indicates
      that these are composed of layers of slow, intermediate and fast muscle fibres.
      Anti-GABA immunohistochemistry shows that mainly the intermediate fibres receive
      innervation from putative inhibitory motoneurons. (3). Intracellular recording
      from muscle fibres reveals both excitatory and inhibitory muscle innervation.
      Individual muscle fibres may receive input from more than one inhibitory
      motoneuron, as indicated by different IPSP amplitudes. (4). The motoneuron supply
      of the leg muscles is analysed by retrograde fills of motor nerves. The general
      arrangement of leg motoneurons in the central nervous system and motoneuron
      anatomy conforms to the situation in pterygote insects and decapod crustaceans.
      For example, there are an anterior and a posterior group of leg motoneurons in
      each hemineuromere, and two contralateral somata near the ganglion midline.
      Between 12 and 20 motoneurons are found to supply each muscle. Most motoneuron
      cell bodies supplying a given muscle are arranged in a single cluster with a
      specific location.

PMID- 18088981
TI  - Evolution of the arthropod neuromuscular system. 2. Inhibitory innervation of the
      walking legs of a scorpion: Vaejovis spinigerus (Wood, 1863), Vaejovidae,
      Scorpiones, Arachnida.
AB  - Inhibitory motoneurons which supply the leg musculature are identified and
      characterized in the scorpion, Vaejovis spinigerus (Wood, 1863) (Vaejovidae,
      Scorpiones, Arachnida). (1) Successive intracellular muscle fiber recordings from
      antagonists, and correlation of the monitored inhibitory postsynaptic potentials
      with spikes in motor nerves, suggest supply of the scorpion leg musculature by
      common inhibitory motoneurons. (2) Anti-GABA immunohistochemistry is combined
      with transmission electron microscopy to estimate the number of inhibitory motor
      axons present in the main leg nerve. The number of immunoreactive axons decreases
      toward more distal leg segments, from 14 to 18 in the basis to 6-8 in the tibia.
      No immunoreactive axons are detected beyond the tibia. (3) The distribution of
      putative inhibitory neurons in the subesophageal ganglion mass is determined by
      anti-GABA immunohistochemistry, revealing notable similarities to the situation
      in pterygote insects. This provides a framework for the characterization of the
      inhibitory motoneurons. (4) Backfills from leg nerves are combined with anti-GABA
      immunocytochemistry to identify inhibitory motoneurons in the central nervous
      system. Putative inhibitory motoneurons occur in three clusters per hemi-segment.
      Two clusters are located near the posterior edge of the neuromere, one lateral,
      the other more medial, and both contain ca. 8-10 cell bodies. The third cluster
      consists of two somata located contralaterally, just off the ganglion midline.

PMID- 18088982
TI  - Respiratory organs in wolf spiders: morphometric analysis of lungs and tracheae
      in Pardosa lugubris (L.) (Arachnida, Araneae, Lycosidae).
AB  - The respiratory system of the wolf spider Pardosa lugubris consists of a pair of
      well-developed lungs and four unbranched tube tracheae. We used stereological
      morphometric methods to investigate the morphological diffusing capacity of the
      lungs and of the walls of the tracheae ('lateral diffusing capacity'). We
      examined three groups of female P. lugubris with different mean body masses. The
      barrier thickness of the gas-exchange epithelium of the lungs was 0.17 microm for
      the total diffusion barrier and the calculated oxygen diffusing capacity (D(O2))
      for the lungs was between 12.9 and 13.4 microl min(-1)g(-1)kPa(-1). Measured
      metabolic rates compared with the D(O2) of the lungs result in necessary oxygen
      partial pressure differences of 0.2 kPa during rest and 2.1 kPa during maximum
      measured activity. The diffusion barrier of the entire tracheal walls was 0.31
      0.50 microm and the calculated lateral D(O2) was 0.05-0.2 microl min(-1)g(-1)kPa(
      1). Therefore, tracheae are of no importance for the overall oxygen exchange.
      However, they might be of some importance in local oxygen supply or in overall
      carbon dioxide release. The comparison with the respiratory system of the jumping
      spider Salticus scenicus reveals that the lungs have very similar mass-specific
      D(O2) in both species, and that, in addition, jumping spiders possess a much
      better developed tracheal system.

PMID- 18088983
TI  - Development of the accessory glands in the genital tract of female Teleogryllus
      commodus WALKER (Insecta, Orthoptera).
AB  - The development of the female accessory glands in Teleogryllus commodus was
      studied by detailed morphometric and stereological analyses. In addition, a
      microsurgical method was developed to quantify the gland secretion. The
      morphometric results yield evidence that the glands are subject to a significant
      growth during peak differentiation, starting immediately after the adult moult.
      The gland growth is exclusively caused by a hypertrophy of single gland cells
      with respective volume gains between 400 and 700%. According to the stereological
      results, the volume of mitochondria per cell is marked by an up to fourfold
      increase during peak differentiation. Other cell structures (rER, sER) are
      characterized by a similar propagation behavior. The nucleus and nucleolus grow
      simultaneously with the cell, indicating high production of site-specific
      macromolecules. Infolds of the basal cell membrane cause a progressive
      enlargement of the basal cell surface ensuring an increased uptake of secretory
      precursors from the hemolymph. Quantitative studies show that the total
      production of secretion increases with proceeding age and can be correlated with
      a rising egg-laying activity, starting on the eighth day of adult's life. This
      underlines the main function of the secretion as a lubricant for a facilitated
      transport of the eggs through the ovipositor.

PMID- 18088984
TI  - Ultrastructure and motility pattern of the spermatozoa of Aleochara curtula
      (Coleoptera, Staphylinidae).
AB  - Ultrastructure and motility pattern of spermatozoa of the rove beetle Aleochara
      curtula were examined using electron and light microscopic methods. The
      spermatozoon is about 100 microm long and filiform. The head piece comprises a 5
      microm long triple layered acrosome and 10 microm long nucleus. The flagellum
      consists of a 9+9+2 axoneme, two accessory bodies and two mitochondrial
      derivatives about equal in size but of different shape in their cross sections.
      In both derivatives there are paracrystalline inclusions. The flagellum is
      attached to the head by a 2 microm long centriole adjunct which is characterized
      by its electron dense material that forms a three layered folded lamellar
      structure. When liberated in buffer solution the sperm flagella assume a coiled
      hook-like form with the excentric stiff head protruding in front. The spermatozoa
      are driven through the medium by a small helicoidal wave of high frequency
      superimposed to the bent flagella. The maximum speed measured was 15.2 microm/s.
      The sperm architecture of A. curtula is similar to that of other Aleochara
      species but differs in total length and dimensions of the mitochondrial
      derivatives. For that reason Aleochara sperm can certainly prove useful to study
      the effect of the mitochondrial derivatives on sperm motility.

PMID- 18088985
TI  - Ultrastructural ontogeny of the labial gland apparatus in termite Prorhinotermes
      simplex (Isoptera, Rhinotermitidae).
AB  - The labial glands in Prorhinotermes simplex consist of secretory cells organized
      into acini, water sacs and the ducts connecting the gland parts to the basis of
      the labium. Acini are composed of central and parietal cells. Central cells type
      I contain predominantly lucent vacuoles and are involved probably in hydroquinone
      production. They are lacking in soldiers. Type II central cells produce vacuoles
      of proteinaceous content which are of the same electron density (type IIa) or
      present in more shades (type IIb). Type IIa cells are present in all older
      individuals, whereas type IIb are lacking in soldiers and neotenics. Type III
      cells represent a specific stage of type I cells development, but they are
      definite functional secretory cells in soldiers. Acini of first instar larvae
      contain undifferentiated cells which differentiate into type I cells during the
      second instar. Specific larval central cells start to change into type II cells
      during first instar. The central cells of presoldiers show a transition from the
      pseudergate into the soldier situation. The parietal cells keep a uniform
      structure throughout the whole ontogeny. Only one type of cells form the water
      sacs in all castes. The cells are very flat with scarce organelles. The water sac
      cells produce lipid-like secretion, small lucent vacuoles and bunches of
      angulated vacuoles. The water sac probably functions as water storage organ only.
      Ontogenetical changes in water sac development are small. The acinar ducts
      originate inside the acinus where they are formed by flat cells with rare
      organelles. At the acinus border, cells equipped with mitochondria, microvilli
      and basal invaginations appear. The water sac ducts are formed by flat cells with
      rare organelles. Acinar ducts outside the acinus and water sac ducts are equipped
      with taenidiuam.

PMID- 18088986
TI  - Ultrastructure and receptor cell responses of the antennal grooved peg sensilla
      of Triatoma infestans (Hemiptera: Reduviidae).
AB  - Ultrastructural examination of grooved-peg (GP) sensilla on the antenna of fifth
      instar Triatoma infestans nymphs by scanning electron microscopy and transmission
      electron microscopy reveal that they are 8-18 microm long with a diameter of
      about 2-2.8 microm at the non-articulated base. Some pegs have a terminal pore.
      These double-walled wall-pore (dw-wp) sensilla have an outer cuticular wall with
      13-18 longitudinal grooves at the distal part of the peg. Groove channels are
      present at the bottom of the grooves from which radial spoke channels lead into
      the inner sensillum-lymph cavity. A dendrite sheath connects the tip of the
      thecogen cell to the inner cuticular wall thus forming separated outer and inner
      sensillum-lymph cavities. Four or five bipolar receptor cells are ensheathed
      successively within the GP sensilla by the thecogen cell, trichogen and tormogen
      cells. The inner dendritic segments of each sensory cell give rise at the ciliary
      constriction to an unbranched outer dendritic segment which can reach the tip of
      the sensillum. Electrophysiological recordings from the GP sensilla indicate that
      they house NH3, short-chain carboxylic acid and short-chain aliphatic amine
      receptor cells and can be divided into three functional sub-types (GP 1-3). All
      GP sensilla carry a receptor cell excited by aliphatic amines, such as
      isobutylamine, a compound associated with vertebrate odour. GP type 1 and 2
      sensilla house, in addition, an NH3-excited cell whereas the type 2 sensilla also
      contains a short-chain carboxylic acid receptor. No cell particularly sensitive
      to either NH3 or carboxylic acids was found in the grooved-peg type 3 sensilla.
      GP types 1, 2 and 3 represent ca. 36, 10 and 43% of the GP sensilla,
      respectively, whereas the remaining 11% contain receptor cells that manifest
      normal spontaneous activity but do not respond to any of the afore mentioned
      stimuli.

PMID- 18088987
TI  - Novel use of hair sensilla in acoustic stridulation by New Zealand giant wetas
      (Orthoptera: Anostostomatidae).
AB  - Sound production in New Zealand giant wetas (Orthoptera: Anostostomatidae)
      includes a femoro-abdominal mechanism, a ticking sound when alarmed (mechanism
      unknown) and, in two species (Deinacrida rugosa and Deinacrida parva), a tergo
      tergal mechanism on the dorsal overlapping surfaces of abdominal tergites. The
      tergo-tergal mechanism consists of bilaterally paired patches of short curved
      spines on the dorsal anterior margins of tergites II-V, rubbed by opposing
      patches of articulated hair sensilla on the underside of each overlapping
      tergite. The latter are extremely robust, modified mechanoreceptors inserted at
      an acute angle onto raised bases which greatly restrict movement. They rub
      sideways against the underlying spines and produce sound during telescopic
      abdominal contraction which accompanies defence leg kicking stridulation.
      Movement analysis showed that the abdominal tergites contract asynchronously
      during stridulation. Sound is produced during both phases of telescoping. Femoro
      abdominal sound comprises loud clicks of broadband sound principally below 10
      kHz; tergo-tergal sound is a softer hiss spreading broadly from 10 kHz to the
      ultrasonic above 20 kHz. We propose that the tergo-tergal mechanism may have
      evolved under predation pressure by the ground gleaning short tailed bat endemic
      to New Zealand. The use of mechanosensory hair sensilla for sound production is
      rare in arthropods.

PMID- 18088988
TI  - Comparison of turnover in the olfactory organ of early juvenile stage and adult
      Caribbean spiny lobsters.
AB  - Proliferation and turnover of neurons occurs in the olfactory systems of many
      animals. In this study, we examined developmental changes in turnover in the
      olfactory organ of the Caribbean spiny lobster Panulirus argus by examining two
      life-history stages-early juveniles and young adults. Turnover was compared using
      external morphology of the olfactory organ before and after molting to determine
      addition and loss of aesthetascs and other chemosensilla, and BrdU labeling to
      identify newly proliferated cells. The number of olfactory receptor neurons
      (ORNs) innervating each aesthetasc increased only slightly over development, but
      there was a net increase of olfactory sensory units (i.e. aesthetascs and their
      ORNs) at each molt. This increase was similar in early juveniles and young adults
      when expressed as absolute number of ORNs neurons but greater in early juveniles
      when expressed as a proportion of existing ORNs. The net increase in olfactory
      sensory units in early juveniles is due solely to addition, since virtually no
      aesthetascs are lost. In contrast, the net increase in olfactory sensory units in
      adults reflects addition of new units accompanied by considerable loss of old
      units. These developmental changes result in expansive enlargement of the
      olfactory organ without turnover in early juveniles, and a more modest growth
      combined with continuous turnover and replenishment of ORNs in adults.

PMID- 18088989
TI  - Ultrastructure of the male reproductive accessory glands in the medfly Ceratitis
      capitata (Diptera: Tephritidae) and preliminary characterization of their
      secretions.
AB  - The morphology and the ultrastructure of the male accessory glands and
      ejaculatory duct of Ceratitis capitata were investigated. There are two types of
      glands in the reproductive apparatus. The first is a pair of long, mesoderm
      derived tubules with binucleate, microvillate secretory cells, which contain
      smooth endoplasmic reticulum and, in the sexually mature males, enlarged
      polymorphic mitochondria. The narrow lumen of the gland is filled with dense or
      sometimes granulated secretion, containing lipids. The second type consists of
      short ectoderm-derived glands, finger-like or claviform shaped. Despite the
      different shape of these glands, after a cycle of maturation, their epithelial
      cells share a large subcuticular cavity filled with electron-transparent
      secretion. The ejaculatory duct, lined by cuticle, has epithelial cells with a
      limited involvement in secretory activity. Electrophoretic analysis of accessory
      gland secretion reveals different protein profiles for long tubular and short
      glands with bands of 16 and 10kDa in both types of glands. We demonstrate that a
      large amount of accessory gland secretion is depleted from the glands after 30min
      of copulation.

PMID- 18088991
TI  - A comment from the editors. Evolution of the arthropod nervous system.

PMID- 18088990
TI  - Female reproductive system of the decapitating fly Pseudacteon wasmanni Schmitz
      (Diptera: Phoridae).
AB  - Pseudacteon wasmanni is a South American decapitating fly that parasitizes
      workers of Solenopsis fire ants. We used light microscopy (historesin serial
      sectioning stained with Haematoxylin/Eosin) and scanning electron microscopy to
      show and analyze internal and whole external views of the female reproductive
      system. All specimens analyzed (n=9) by light microscopy showed post-vitellogenic
      oocytes inside the ovaries. The lack of typical follicles (oocyte-nurse cell
      complexes) in all specimens suggests that oogenesis occurs during the pupal
      stage. The total number of eggs found ranged from 31 to 280 (X=142+/-73, SD). The
      egg has a slugform or torpedo shape (about 130 by 20 microm) with a pointed apex
      at the posterior pole as defined by the fly; the micropyle appears to be in a
      depression or invagination at the anterior pole. An acute hypodermic-like
      ovipositor is evaginated from the hard sclerotized external genitalia during egg
      laying. The existence of a muscular bulb associated with the end of the common
      oviduct suggests that the egg is injected into the ant's body by a strong
      contraction of the bulb which probably is stimulated by bending of several
      ventral sensilla. During contraction, the abdomen extends out along a large fold
      between the sixth and seventh tergites in such a way that the sclerotized
      genitalia is rotated ventrally into a slightly anterior orientation in
      preparation for oviposition.

PMID- 18088992
TI  - Development of the arthropod nervous system: variations on a common theme?
      Introduction.

PMID- 18088993
TI  - Neurogenesis in the spider: new insights from comparative analysis of
      morphological processes and gene expression patterns.
AB  - While there is a detailed understanding of neurogenesis in insects and partially
      also in crustaceans, little is known about neurogenesis in chelicerates. In the
      spider Cupiennius salei Keyserling, 1877 (Chelicerata, Arachnida, Araneae)
      invaginating cell groups arise sequentially and in a stereotyped pattern
      comparable to the formation of neuroblasts in Drosophila melanogaster Meigen,
      1830 (Insecta, Diptera, Cyclorrhapha, Drosophilidae). In addition, functional
      analysis revealed that in the spider homologues of the D. melanogaster proneural
      and neurogenic genes control the recruitment and singling out of neural
      precursors like in D. melanogaster. Although groups of cells, rather than
      individual cells, are singled out from the spider neuroectoderm which can thus
      not be homologized with the insect neuroblasts, similar genes seem to confer
      neural identity to the neural precursor cells of the spider. We show here that
      the pan-neural genes snail and the neural identity gene Kruppel are expressed in
      neural precursors in a heterogenous spatio-temporal pattern that is comparable to
      the pattern in D. melanogaster. Our data suggest that the early genetic network
      involved in recruitment and specification of neural precursors is conserved among
      insects and chelicerates.

PMID- 18088994
TI  - Ontogeny of the ventral nerve cord in malacostracan crustaceans: a common plan
      for neuronal development in Crustacea, Hexapoda and other Arthropoda?
AB  - This review sets out to summarize our current knowledge on the structural layout
      of the embryonic ventral nerve cord in decapod crustaceans and its development
      from stem cell to the mature structure. In Decapoda, neuronal stem cells, the
      neuroblasts, mostly originate from ectodermal stem cells, the ectoteloblast, via
      a defined lineage. The neuroblasts undergo repeated asymmetric division and
      generate ganglion mother cells. The ganglion mother cells later divide again to
      give birth to ganglion cells (neurons) and there is increasing evidence now that
      ganglion mother cells divide again not only once but repeatedly. Various other
      aspects of neuroblast proliferation such as their temporal patterns of mitotic
      activity and spatial arrangement as well as the relation of neurogenesis to the
      development of the segmental appendages and maturation of motor behaviors are
      described. The link between cell lineage and cell differentiation in Decapoda so
      far has only been established for the midline neuroblast. However, there are
      several other identified early differentiating neurons, the outgrowing neurites
      of which pioneer the axonal scaffold within the neuromeres of the ventral nerve
      cord. The maturation of identified neurons as examined by immunohistochemistry
      against their neurotransmitters or engrailed, is briefly described. These
      processes are compared to other Arthropoda (including Onychophora, Chelicerata,
      Diplopoda and Hexapoda) in order to shed light on variations and conserved motifs
      of the theme 'neurogenesis'. The question of a 'common plan for neuronal
      development' in the ventral nerve cords of Hexapoda and Crustacea is critically
      evaluated and the possibility of homologous neurons arising through divergent
      developmental pathways is discussed.

PMID- 18088995
TI  - Regulation of life-long neurogenesis in the decapod crustacean brain.
AB  - This article provides an overview of our understanding of life-long neurogenesis
      in the decapod crustacean brain, where the proliferation of sensory and
      interneurons is controlled by many of the same factors as is neurogenesis in the
      mammalian brain. The relative simplicity, spatial organization and accessibility
      of the crustacean brain provide opportunities to examine specific neuronal
      pathways that regulate neurogenesis and the sequence of gene expression that
      leads to neuronal differentiation.

PMID- 18088996
TI  - Commissure formation in the embryonic insect brain.
AB  - The primary axon scaffold of the insect brain is established early in
      embryogenesis and comprises a preoral protocerebral commissure, a postoral
      tritocerebral commissure and longitudinal fiber pathways linking the two. In both
      grasshopper and fly its form is approximately orthogonal and is centered around
      the stomodeum. We show how pioneer fibers from the protocerebrum and
      tritocerebrum cross the brain midline directly via their respective commissures.
      The deutocerebrum, however, lacks its own commissure and we describe how
      deutocerebral pioneers circumnavigate the gut to cross the midline either via the
      protocerebral commissure or the tritocerebral commissure. In contrast to all
      other commissures of the central nervous system, the protocerebral commissure
      persists, albeit in reduced form, in the commissureless mutation in the fly.
      Besides the com gene, a further, as yet unidentified, mechanism must regulate
      this commissure. The formation of the tritocerebral commissure involves labial, a
      member of the Hox gene group. Genetic rescue experiments in labial mutants reveal
      that the formation of this commissure can be rescued by all other Hox genes
      except Abdominal-B. However, only in the labial and Deformed null mutants are the
      commissures associated with the respective expression domains (tritocerebral,
      mandibular, respectively) absent. This suggests that the molecular mechanisms
      regulating postoral brain commissure formation are distinct from those in the
      neuromeres of the ventral nerve cord.

PMID- 18088997
TI  - Development and evolution of the insect mushroom bodies: towards the
      understanding of conserved developmental mechanisms in a higher brain center.
AB  - The insect mushroom bodies are prominent higher order neuropils consisting of
      thousands of approximately parallel projecting intrinsic neurons arising from the
      minute basophilic perikarya of globuli cells. Early studies described these
      structures as centers for intelligence and other higher functions; at present,
      the mushroom bodies are regarded as important models for the neural basis of
      learning and memory. The insect mushroom bodies share a similar general
      morphology, and the same basic sequence of developmental events is observed
      across a wide range of insect taxa. Globuli cell progenitors arise in the embryo
      and proliferate throughout the greater part of juvenile development. Discrete
      morphological and functional subpopulations of globuli cells (or Kenyon cells, as
      they are called in insects) are sequentially produced at distinct periods of
      development. Kenyon cell somata are arranged by age around the center of
      proliferation, as are their processes in the mushroom body neuropil. Other
      aspects of mushroom body development are more variable from species to species,
      such as the origin of specific Kenyon cell populations and neuropil
      substructures, as well as the timing and pace of the general developmental
      sequence.

PMID- 18088998
TI  - Early steps in building the insect brain: neuroblast formation and segmental
      patterning in the developing brain of different insect species.
AB  - In insects, morphological, molecular and genetic studies have provided a detailed
      insight into the ontogenetic processes that shape the ventral nerve cord. On the
      other hand, owing to its complexity and less obvious segmental composition, the
      knowledge about the development of the brain is still fragmentary. A promising
      approach towards gaining insight into fundamental processes underlying brain
      development is the comparison of embryonic brain development among different
      insect species. However, so far such comparative analyses are scarce. In this
      review, we summarize and compare data on the early steps in brain formation in
      different hemi- and holometabolous insects. We show that basic aspects of the
      spatial and temporal development of the embryonic brain neuroblast pattern are
      conserved among insects. Furthermore, we compare the number and proliferation
      patterns of neuroblasts related to major neuropil structures such as mushroom
      bodies, central complex, and antennal lobe. Finally, comparing the expression
      patterns of engrailed in different species, and considering new data from
      Drosophila melanogaster, we discuss the segmental organization of the insect
      brain.

PMID- 18088999
TI  - Spatial and temporal pattern of neuroblasts, proliferation, and Engrailed
      expression during early brain development in Tenebrio molitor L. (Coleoptera).
AB  - In insects, the knowledge of embryonic brain development is still fragmentary,
      and comparative data are scarce. In this study, we explored aspects of embryonic
      brain development in the coleopteran Tenebrio molitor. A detailed description is
      provided of the spatial and temporal pattern of the embryonic brain neuroblasts
      during 18-60% of embryonic development. Approximately 125 brain NBs have been
      identified in each hemisphere of the brain at about 40% of embryonic development.
      A subset of five neuroblasts, among them the two progenitors of the mushroom
      bodies and two progenitors of the larval antennal lobe, are morphologically
      identifiable by their larger size. As revealed by incorporation of BrdU, their
      mitotic behaviour is distinct from that of all other brain NBs, exhibiting an
      extended period of proliferation into postembryonic stages, and a significantly
      higher rate of division. To gain insight into the segmental organization of the
      T. molitor brain, Engrailed expression was examined in the head ectoderm and the
      deriving components of the CNS (including neuroblasts and their progeny) at
      different stages of embryonic development.

PMID- 18089000
TI  - The urbilaterian brain: developmental insights into the evolutionary origin of
      the brain in insects and vertebrates.
AB  - Classical phylogenetic, neuroanatomical and neuroembryological studies propose an
      independent evolutionary origin of the brains of insects and vertebrates.
      Contrasting with this, data from three sets of molecular and genetic analyses
      indicate that the developmental program of brains of insects and vertebrates
      might be highly conserved and suggest a monophyletic origin of the brain of
      protostomes and deuterostomes. First, recent results of molecular phylogeny imply
      that none of the currently living animals correspond to evolutionary
      intermediates between protostomes and deuterostomes, thus making it impossible to
      infer the morphological organization of an ancestral bilaterian brain from living
      specimens. Second, recent molecular genetic evidence provides support for the
      body axis inversion hypothesis, which implies that a dorsoventral inversion of
      the body axis occurred in protostomes versus deuterostomes, leading to the
      inverted location of neurogenic regions in these animal groups. Third, recent
      developmental genetic analyses are uncovering the existence of structurally and
      functionally homologous genes that have comparable and interchangeable functions
      in early brain development in insect and vertebrate model systems. Thus,
      development of the anteriormost part of the embryonic brain in both insects and
      vertebrates depends upon the otd/Otx and ems/Emx genes; development of the
      posterior part of the embryonic brain in both insects and vertebrates involves
      homologous control genes of the Hox cluster. These findings, which demonstrate
      the conserved expression and function of key patterning genes involved in
      embryonic brain development in insects and vertebrates support the hypothesis
      that the brains of protostomes and deuterostomes are of monophyletic,
      urbilaterian origin.

PMID- 18089001
TI  - The ultrastructure and function of the silk-producing basitarsus in the Hilarini
      (Diptera: Empididae).
AB  - The tribe Hilarini (Diptera: Empididae), commonly known as dance flies, can be
      recognised by their swollen silk-producing prothoracic basitarsus, a male
      secondary sexual characteristic. The ultrastructure and function of the silk
      producing basitarsus from one undescribed morphospecies of Hilarini, 'Hilarempis
      20', is presented. Male H. 20 collect small parcels of diatomaceous algae from
      the surface of freshwater creeks that they bind with silk produced by the gland
      in the basitarsus. The gift is then presented to females in a nearby swarm,
      composed predominately of females. The basitarsus houses approximately 12 pairs
      of class III dermal glandular units that congregate on the ventral side of the
      cavity. Each gland cell has a large extracellular lumen where secretion
      accumulates. The lumen drains to the outside via a conducting canal encompassed
      by a canal cell and a duct extending through the shaft of a specialised secretory
      spine. The secretory spines lie in pairs in a ventral groove that runs the length
      of the basitarsus. A comparison of the basitarsal secretory spines with sensilla
      on the basitarsi of non gland-bearing legs of males, and with non gland-bearing
      prothoracic basitarsi of females, suggests that the glandular units are derived
      from contact chemosensory sensilla.

PMID- 18089002
TI  - Post-embryonic development of cuticular caps of campaniform sensilla of the
      cockroach leg: potential implications in scaling force detection.
AB  - All animals generate progressively larger forces as they increase in size and
      mass. Their abilities to detect these forces must be similarly adjusted. In
      insects, campaniform sensilla monitor strains in the exoskeleton and provide
      information about forces acting upon the legs. Each sensory neuron possesses a
      dendrite that inserts into a cuticular cap in the exoskeleton. The cap is the
      site of mechanotransduction. We measured the sizes and numbers of receptor caps
      on the cockroach hindleg at different developmental stages. Our goal was to
      identify morphological features that could be correlated with the range of forces
      that must be detected. As cockroaches increase in size through successive molts,
      the number of cuticular caps in each group increases. The tibial group, for
      example, has two sensilla in first instar animals and 10-12 in the adult. There
      is also an increase in the range of cap sizes within each group. Observations of
      animals and their molted exoskeletons suggest that this increase occurs as the
      caps of existing receptors increase in size and smaller ones are added with each
      molt. These changes may be important in increasing the range of forces the
      receptors can signal while retaining sensitivity to low levels of force.

PMID- 18089003
TI  - The peripheral and central antennular pathway of the Caribbean stomatopod
      crustacean Neogonodactylus oerstedii.
AB  - Although stomatopod crustaceans use their chemical senses in many facets of
      behavior, little is known about their chemosensory neural pathways, especially in
      comparison to the better-studied decapod crustaceans. We examined the stomatopod
      Neogonodactylus oerstedii to determine organizational aspects of peripheral and
      central neural pathway of antennules, which is a major chemosensory organ. We
      describe the three flagella of the triramous antennule as the medial,
      dorsolateral, and ventrolateral flagella. The primary branch point is between the
      medial flagellum and lateral flagella, and the secondary branch point is at the
      junction of the dorsolateral and ventrolateral flagella. The antennule bears at
      least three types of setae, based on their external morphology. Simple setae are
      present only on the medial flagellum and ventrolateral flagellum, organized as a
      tuft of 10-15 setae on each flagellar annulus. Aesthetasc setae and asymmetric
      setae occur only on the distal annuli of the dorsolateral flagellum, with each
      annulus bearing a row of three aesthetascs and one asymmetric seta. DiI fills of
      the antennular nerve near the junction of the flagella show that sensory neurons
      in the antennular flagella project to two neuropils in the ipsilateral midbrain
      the olfactory lobe (OL) and lateral antennular neuropil (LAN). The OL is
      glomerular and has rich serotonergic innervation, a characteristic of the OL in
      decapods. The LAN is bi-lobed and stratified as it is in decapods. However, the
      LAN of stomatopods differs from that of decapods in being relatively large and
      containing extensive serotonergic innervation. The median antennular neuropil of
      stomatopods has sparse serotonergic innervation, and it is more diffusely
      organized compared to decapods. No accessory lobes were found in N. oerstedii.
      Thus, the stomatopod antennular flagella have the same two, highly organized
      parallel pathways common to decapods-the OL pathway and the LAN pathway.

PMID- 18089004
TI  - Mouthpart morphology and stylet penetration of host plants by the glassy-winged
      sharpshooter, Homalodisca coagulata, (Homoptera: Cicadellidae).
AB  - The ultrastructural morphology of the mouthparts of the glassy-winged
      sharpshooter, Homalodisca coagulata, and method of plant penetration was examined
      using light microscopy, scanning electron microscopy, and transmission electron
      microscopy methods. The gross morphology of the labrum, labium, and stylet
      fascicle was consistent with what has been described for other plant-sucking
      homopterans. The ultrastructural examination of the mouthparts revealed unique
      details that have previously gone unreported. Several types of sensilla-like
      structures having the form of pegs and multi-lobed objects were identified on the
      outer surfaces of the labrum and within the labial groove. Dendritic canals
      terminated in an extensive network of smaller canals at the distal tip of the
      maxillary stylets below a series of surface denticles suggesting that this area
      may have a sensory function associated with locating xylem elements of host
      plants. Examination of salivary sheath pathways established that 65% of the plant
      penetrations by this insect terminated in the xylem vessels of the host plant.
      Probing by the insect was largely intracellular and terminal branching of a
      single probe site was common. Plant surface feeding sites varied with the stage
      of development which correlates with the depth of the xylem vessels and the
      length of the maxillary stylets of the various instars.

PMID- 18089005
TI  - Ultrastructure of epidermal glands in neotenic reproductives of the termite
      Prorhinotermes simplex (Isoptera: Rhinotermitidae).
AB  - The ultrastructure of epidermal glands in neotenic reproductives of
      Prorhinotermes simplex is described and their development is compared among young
      and old neotenics of both sexes. Secretory cells forming the epidermal gland are
      attached to the cuticle all over the body. The glands are formed by class 1 and
      class 3 secretory cells and corresponding canal cells with secretory function.
      Class 1 cells are sandglass-like and class 3 secretory units are located among
      them. Class 1 cells contain predominantly tubular endoplasmic reticulum, the
      major part represents the smooth and the minor the rough form. Numerous electron
      dense granules occur in the cytoplasm, they are always disintegrated prior to be
      released. Class 3 secretory cells contain a large amount of vacuoles, which are
      always lucent in males while newly produced vacuoles are dense in females. Dense
      vacuoles are frequently transformed into lucent ones before being released. Canal
      cells are locally equipped with microvilli. The conducting canal is surrounded by
      an electron dense secretion of regular inner structure. The cytoplasm of the
      canal cell contains numerous mitochondria, rough endoplasmic reticulum and a
      large proportion of microtubules. The young neotenic reproductives differ from
      the old ones by a lower amount of secretory products. Epidermal glands probably
      produce substances inhibiting the occurrence of superfluous reproductives.

PMID- 18089006
TI  - Development of the labial gland of the ponerine ant Pachycondyla obscuricornis
      (Hymenoptera, Formicidae) during the pupal stage.
AB  - The labial gland of adult workers of the ant Pachycondyla obscuricornis is made
      up of many acini, each consisting of one central cell surrounded by approximately
      10 parietal cells. Both cell types are associated with a system of ramified
      canaliculi that remove the secretion towards a ductule outside the acinus. These
      ductules, each associated with one acinus, fuse together and form a ramified
      system of ducts, ending in two paired ducts. These paired ducts widen to form a
      reservoir and anteriorly join into a common unpaired duct, which ends at the base
      of the labium. During development in the pupal stage, epithelial acini are formed
      first, consisting of a monolayered epithelium lining a central lumen. In these
      acini, one cell grows out to become the central cell, while the others will re
      arrange around it to form the parietal cells. At the end of the pupal stage, the
      canaliculi are formed inside the acini by the central and parietal cells that
      secrete a lipidic substance and a cuticle. This gland type, which also occurs in
      some other Hymenoptera, is structurally different from the epithelial glands and
      the glands consisting of bicellular units, that have been traditionally
      distinguished until now.

PMID- 18089007
TI  - Morphological aspects of Culex quinquefasciatus salivary glands.
AB  - The salivary glands of Culex quinquefasciatus female mosquitoes are paired organs
      composed of two lateral lobes with proximal and distal secretory portions, and a
      medial lobe. All portions comprise a simple epithelium that surrounds a salivary
      duct. In the apical portion of the medial lobe, non-secretory cells strongly
      resemble cells involved in ion and water transport. The general architecture of
      the secretory portions is similar between lobes. The appearance of the secretory
      material and the morphological aspect of the apical cell membrane are the most
      distinctive features among the three secretory portions. Cells in the lateral
      proximal lobe display thin membrane projections extending into a translucent and
      finely filamentous secretory product. At the lateral distal portion, the apical
      cell membrane forms an intricate meshwork that encloses a dark secretory product.
      Medial lobe secretory cells also contain secretory cavities surrounded by
      intracytoplasmic vesicles, all containing a very dark and uniform product.
      Scattered cells holding numerous vacuoles, some of them containing a small and
      electron-dense granule eccentrically located and resembling those of the diffuse
      endocrine system, are frequently observed in the periphery of all secretory
      portions. Immunofluorescence assays revealed that the distal portion of the
      lateral lobes contains apyrase, an enzyme putatively responsible for platelet
      aggregation inhibition, diffusely distributed in the cell cytoplasm.

PMID- 18089008
TI  - Comparative midgut ultrastructure of unfed larvae and adult mites of
      Platytrombidium fasciatum (C.L. Koch, 1836) and Camerotrombidium pexatum (C.L.
      Koch, 1837) (Acariformes: Microtrombidiidae).
AB  - The midgut of unfed larvae and adult mites of Platytrombidium fasciatum (C.L.
      Koch, 1836) and Camerotrombidium pexatum (C.L. Koch, 1937) (Acariformes:
      Microtrombidiidae) was investigated by electron microscopy. The sac-like midgut
      occupies the entire body volume, ends blindly and is not divided into
      functionally differentiated diverticula or caeca. The midgut walls are composed
      of one type of digestive cell that greatly varies in shape and size. In larvae,
      the lumen of the midgut is poorly recognizable and its epithelium is loosely
      organized, although yolk granules are already utilized. In adults, the midgut
      forms compartments as a result of deep folds of the midgut walls, and the lumen
      is well distinguished. The epithelium is composed of flat, prismatic or club-like
      cells, which may contain nutritional vacuoles and residual bodies in various
      proportions that depend on digestive stages. In both larvae and adult mites,
      parts of cells may detach from the epithelium and float within the lumen. The
      cells contain a system of tubules and vesicles of a trans-Golgi network, whereas
      the apical surface forms microvilli as well as pinocytotic pits and vesicles.
      Lysosome-like bodies, lipid inclusions and some amount of glycogen particles are
      also present in the digestive cells. Spherites (concretions) are not found to be
      a constant component of the digestive cells and in adult mites occur for the most
      parts in the midgut lumen.

PMID- 18089009
TI  - Transmission of symbiotic bacteria Buchnera to parthenogenetic embryos in the
      aphid Acyrthosiphon pisum (Hemiptera: Aphidoidea).
AB  - All phloem-feeding aphids have an absolute requirement for their primary
      bacterial symbionts Buchnera sp. The bacteria are transmitted vertically to
      either embryos in the viviparous morph or to eggs in the oviparous morph, with
      the implication that the symbiont population regularly passes through a genetic
      'bottleneck', i.e. only a small proportion of the maternal symbiont population is
      transmitted to offspring. In this paper, we visualise this process in viviparous
      aphids using a specific immunolabelling technique for Buchnera. The images show a
      stream of bacteria originating from a single mycetocyte and entering the embryo,
      possibly via a membranous conduit, and individual bacterial cells free in the
      haemocoel of the aphid. Staining within the embryo blastoderm suggests over
      expression of antigen, perhaps indicative of rapid bacterial division immediately
      following infection.

PMID- 18089010
TI  - Structure of the ovary in Steingelia (Sternorrhyncha: Coccinea), and its
      phylogenetic implications.
AB  - The paired ovaries of Steingelia gorodetskia are composed of about 100
      telotrophic ovarioles devoid of terminal filaments (scale insect autapomorphy).
      In structure they resemble those of other scale insects, but differ in the
      following details: (a) all ovarioles develop synchronously, (b) they are
      suspended to the lateral oviducts by means of long stalks, (c) the tropharium is
      tubular (unique in scale insects) and (d) consists of 15-35, trophocytes, 2-4
      previtellogenic oocytes that further develop, and numerous somatic prefollicular
      cells, (e) the vitellarium houses 2-4 linearly arranged vitellarial oocytes
      (versus one in most scale insects). Most of these features must be considered as
      plesiomorphic corresponding with the conditions in the most primitive
      Heteroptera. Bacterial endosymbionts have been found in some somatic cells,
      trophocytes, oocytes and in the nutritive cord. Present results support the
      opinion, based on external morphology, that the Steingeliidae are closely related
      to the Ortheziidae, Xylococcidae and Matsucoccidae.

PMID- 18089011
TI  - Comparative study of the defensive behavior and morphology of the gland opening
      area among harvestmen (Arachnida, Opiliones, Gonyleptidae) under a phylogenetic
      perspective.
AB  - The arachnids of the order Opiliones (harvestmen) have a pair of scent glands
      opening at the sides of the body, the substances of which are used in defense.
      Several types of behavioral, morphological and chemical defensive mechanisms have
      been assigned to the order as a whole, although some of these tactics were
      restricted to particular groups. Only around 25 species have been studied from
      this perspective so far. In the present paper, we analyzed 33 species (mostly
      from the largest harvestmen family, the Gonyleptidae) aiming at recognizing the
      usefulness of the defensive characters in taxonomy and evolutionary biology. We
      observed the morphology of the gland opening (ozopore) area and the defensive
      behavior, and their relationship, and mapped these traits on an available
      phylogenetic hypothesis of relationship within Gonyleptidae. As outgroups, we
      analyzed Cosmetidae and Stygnidae. Combining the observed behavioral characters
      of the emission of defensive secretion (near the ozopore, with liquid
      displacement through an integumentary groove, or in form of a jet) with the
      morphological types of the gland opening (direction of the integumentary dome
      that surrounds the gland opening, presence of two openings and the relationship
      between their sizes, and presence of a V-shaped cut at the anterior opening), we
      recognized eight patterns. In addition, we could examine the evolution of such
      traits within Gonyleptidae.

PMID- 18089012
TI  - Flexible ovipositor sheaths in parasitoid Hymenoptera (Insecta).
AB  - The structure of the ovipositor sheaths is examined in a number of parasitic
      wasps as well as a few non-parasitic taxa. Parasitic wasps in the families
      Aulacidae, Braconidae, Ichneumonidae, Megalyridae, and Stephanidae with a very
      elongate, external ovipositor have the lateral wall of the sheath finely
      transversely subdivided by narrow furrows. This makes the sheath highly flexible,
      allowing it to support the ovipositor proper during ovipositing. The taxa having
      such a flexible sheath all drill into wood to lay their eggs. Support at the tip
      of the ovipositor is crucial in the initial stages of oviposition. The flexible
      ovipositor sheath is possibly a very ancient trait, arising prior to the
      radiation of extant Apocrita. This is corroborated by their presence in fossil
      Hymenoptera from the Upper Jurassic. The occurrence of short and/or concealed
      ovipositors with rigid sheaths in many extant apocritan taxa must therefore be
      assumed to be the result of multiple reversals.

PMID- 18089013
TI  - Embryonic development of the sensory innervation of the clypeo-labral complex:
      further support for serially homologous appendages in the locust.
AB  - The clypeo-labrum, or upper lip, of insects is intimately involved in feeding
      behavior and is accordingly endowed with a rich sensory apparatus. In the present
      study we map the temporal appearance of all major clusters of sensory cells on
      this structure in the locust during the first half of embryogenesis. The
      identities of these sensory cell clusters were defined according to the origin of
      the branching point of their axons from the labral sensory nerve as seen at mid
      embryogenesis. The first sensory cells to differentiate from the labral
      epithelium do so at stereotypic sites beginning at around 32% of embryogenesis.
      Bilaterally symmetrical clusters of differentiated neurons rapidly appear and
      pioneering of the labral sensory nerve on each side is performed by a specific
      cell from each cluster. This cell directs its axon anteriorly towards a
      bilaterally symmetrical pair of cells, the frontal commissure pioneers, on either
      side of the developing frontal ganglion. The final trajectory of the sensory
      nerve within the labrum closely matches the pattern of Repo-expressing glial
      cells. The majority of the sensory cell clusters differentiate during
      embryogenesis, but the number of sensory cells in some clusters are modified
      significantly during postembryonic development. Comparing the innervation pattern
      of the clypeo-labrum with that of other mouthparts and the leg at mid
      embryogenesis, we find a striking similarity in organization which we interpret
      as support for the homologous appendage hypothesis.

PMID- 18089014
TI  - Development of neural lineages derived from the sine oculis positive eye field of
      Drosophila.
AB  - The Anlage of the Drosophila visual system, called eye field, comprises a domain
      in the dorso-medial neurectoderm of the embryonic head and is defined by the
      expression of the early eye gene sine oculis (so). Beside the eye and optic lobe,
      the eye field gives rise to several neuroblasts that contribute their lineages to
      the central brain. Since so expression is only very short lived, the later
      development of these neuroblasts has so far been elusive. Using the P-element
      replacement technique [Genetics, 151 (1999) 1093] we generated a so-Gal4 line
      driving the reporter gene LacZ that perdures in the eye field derived cells
      throughout embryogenesis and into the larval period. This allowed us to
      reconstruct the morphogenetic movements of the eye field derived lineages, as
      well as the projection pattern of their neurons. The eye field produces a dorsal
      (Pc1/2) and a ventral (Pp3) group of three to four neuroblasts each. In addition,
      the target neurons of the larval eye, the optic lobe pioneers (OLPs) are derived
      from the eye field. The embryonically born (primary) neurons of the Pp3 lineages
      spread out at the inner surface of the optic lobe. Together with the OLPs, their
      axons project to the dorsal neuropile of the protocerebrum. Pp3 neuroblasts
      reassume expression of so-Gal4 in the larval period and produce secondary neurons
      whose axonal projection coincides with the pattern formed by the primary Pp3
      neurons. Several other small clusters of neurons that originate from outside the
      eye field, but have axonal connections to the dorsal protocerebrum, also express
      so and are labeled by so-Gal4 driven LacZ. We discuss the dynamic pattern of the
      so-positive lineages as a tool to reconstruct the morphogenesis of the larval
      brain.

PMID- 18089015
TI  - Central projections of olfactory receptor neurons from single antennal and palpal
      sensilla in mosquitoes.
AB  - In insects, olfactory receptor neurons (ORNs) are located in cuticular sensilla,
      that are present on the antennae and on the maxillary palps. Their axons project
      into spherical neuropil, the glomeruli, which are characteristic structures in
      the primary olfactory center throughout the animal kingdom. ORNs in insects often
      respond specifically to single odor compounds. The projection patterns of these
      neurons within the primary olfactory center, the antennal lobe, are, however,
      largely unknown. We developed a method to stain central projections of intact
      receptor neurons known to respond to host odor compounds in the malaria mosquito,
      Anopheles gambiae. Terminal arborizations from ORNs from antennal sensilla had
      only a few branches apparently restricted to a single glomerulus. Axonal
      arborizations of the different neurons originating from the same sensillum did
      not overlap. ORNs originating from maxillary palp sensilla all projected into a
      dorso-medial area in both the ipsi- and contralateral antennal lobe, which
      received in no case axon terminals from antennal receptor neurons. Staining of
      maxillary palp receptor neurons in a second mosquito species (Aedes aegypti)
      revealed unilateral arborizations in an area at a similar position as in An.
      gambiae.

PMID- 18089016
TI  - Development of a gregarious ectoparasitoid, Euplectrus separatae (Hymenoptera;
      Hymenoptera: Eulophidae), that parasitizes Pseudaletia separata (Lepidoptera:
      Noctuidae).
AB  - Euplectrus separatae is a gregarious ectoparasitoid that parasitizes Pseudaletia
      separata during its third to sixth (last) instars. The eggs of the parasitoid are
      fixed on the integument of the host dorsolaterally with a hard substance like a
      piling driven into the integument by the female wasp at the time of oviposition.
      The first instar of the parasitoid, which hatches three days after oviposition is
      nourished by ingesting the hemolymph of the host, and ecdyses to the second
      stadium six days after oviposition. Many hemocytes and epidermal cells were found
      assembled under the piling and places where a parasitoid had attached its mouth,
      suggesting that the host had repaired the integument destroyed by the parasitoid.
      Botryoidal tissue, which stained well with hematoxylin, began to develop from
      four days after oviposition and became gradually larger with development.
      Botryoidal tissue appears to function as a secretory organ for thread and a
      storage organ for nutrients. Seven days after oviposition, the parasitoid larvae
      migrate down from the dorsal surface to the ventral side of the host. Just before
      descending they ecdyse to the third stadium and kill the host during their
      migration. If all parasitoid larvae were removed artificially from the host
      before they migrate, the host did not die. However, removing the parasitoids
      after they had started to migrate did not prevent the death of the host.
      Transmission electron microscopic (TEM) observation of salivary glands of a
      parasitoid larva before migrating revealed that the salivary gland was composed
      of cells that were rich in rough surfaced endoplasmic reticulum (rough-ER) with
      many ribosomes and cells that were filled with a lot of vacuoles just before
      their collapse. After moving from the host body, the parasitoid larvae doubled in
      weight by ingesting the tissue of the host and then spun a cocoon. Almost all
      host tissues were consumed for growth of the parasitoid, like an idiobiont
      parasitoid.

PMID- 18089017
TI  - The circulatory system in Phreatoicidea: implications for the isopod ground
      pattern and peracarid phylogeny.
AB  - The circulatory systems of four species of Phreatoicidea and two species of
      Oniscidea were studied on the basis of serial semi-thin sections and a corrosion
      cast method. A 3D computer reconstruction was used to visualize the circulatory
      organs in the head of the Phreatoicidea. In the Phreatoicidea, the circulatory
      system consists of a longitudinal dorsal heart extending from the third thoracic
      to the border between the fourth and fifth pleonal segments. It is equipped with
      two pairs of asymmetrically arranged ostia, while five pairs of lateral cardiac
      arteries and an unpaired anterior aorta extend from the heart. Entering the head,
      the aorta is accompanied by the two first lateral arteries, which supply the
      muscles of the mandibles. Four pairs of arteries branch off the aorta to supply
      both pairs of antennae, the eyes, and sinuses in the head. In addition, several
      minute capillaries extend from the aorta to supply the brain. The two oniscidean
      species were re-investigated with regard to some characters which have been
      controversially discussed. In these species, the heart extends from the border
      between the fifth and sixth thoracic segments to the fifth pleonal segment. Five
      pairs of lateral cardiac arteries and the unpaired anterior aorta lead off the
      heart. A ventral vessel was not observed. The ground pattern of the circulatory
      system in isopods is reconstructed with greater reliability through optimisation
      of its characters based on proposed phylogenetic relationships. The results do
      not support a phylogenetic position of the Isopoda as basal Peracarida or even
      basal Eumalacostraca.

PMID- 18089018
TI  - Larval development and morphogenesis of the sea spider Pycnogonum litorale
      (Strom, 1762) and the tagmosis of the body of Pantopoda.
AB  - Aspects of pantopod ontogeny have been known for a long time, but specific
      information is available for only a few species. Our account of the postembryonic
      development of Pycnogonum litorale is based on laboratory-reared individuals and
      SEM studies. We documented particularly all early developmental stages, with
      emphasis on morphogenetic changes of head structures and appendages. In P.
      litorale the protonymphal limbs, the chelicerae and two more uniramous legs,
      degenerate already during the larval phase; only the third one, the ovigers,
      reappears in male juveniles. Other Pantopoda vary in this aspect from retention
      of all three protonymphal appendages to their complete reduction, as in P.
      litorale. Accordingly, the two post-cheliceral larval appendages are separate
      legs in front of the walking legs in the adults, the 'parapalps' and the
      'ovigers', but they do not occur in all pantopods. The scarcity of studies of the
      ontogeny of Pantopoda prevents us from a more conclusive picture, but our data
      are promising to state that additional such studies will increase the usability
      of ontogenetic data for a phylogenetic analysis of Pantopoda, the crown group of
      the Pycnogonida. We also discuss the phylogenetic implications of our data in the
      light of new information from Hox genes and developmental-biological data on body
      segmentation and tagmosis of the Chelicerata. These suggest the homology of
      chelicerae and antenn(ul)ae of other euarthropods. Accepting this, we conclude
      that the adult pycnogonid/pantopod head, the cephalosoma, corresponds to the
      euarthropod head and that the protonymph with three appendage-bearing segments
      may represent an even shorter, possibly phylogenetically older larval type than
      the euarthropod 'head larva' bearing four pairs of appendages. In further
      consequence, the fourth walking legs of Pycnogonida/Pantopoda should correspond
      to the first opisthosomal appendages, the chilaria, of euchelicerates. This
      implies that within Pycnogonida the post-prosomal region became compacted during
      evolution to a single leg-bearing segment plus a tubular end piece. Accordingly,
      neither the anterior nor the posterior functional boundaries of the walking-leg
      region correspond to the original tagma borders.

PMID- 18089019
TI  - Walking on the ceiling: structures, functional principles, and ecological
      implications. Introduction.

PMID- 18089020
TI  - The role of adhesion in prey capture and predator defence in arthropods.
AB  - Adhesive devices are used by arthropods not only in terrestrial locomotion but
      also in prey capture and predator defence. We argue that the physical mechanisms
      involved in both these contexts must mainly be capillarity and the viscosity of
      an adhesive secretion, whereas other mechanisms, such as friction or
      intermolecular forces, are of minor importance. Adhesive prey-capture devices
      might function as passive devices or might be actively extended toward the prey,
      sometimes in a very rapid manner. Adhesive mechanisms used for predator defence
      might involve firm adhesion to the substratum or the discharge of a sticky
      secretion to immobilize the appendages of the opponent. We review the occurrence
      of adhesive devices as employed in both functional contexts across the Arthropoda
      and argue that these mechanisms are of particular importance for slow-moving and
      relatively clumsy life forms. We discuss three case studies in more detail. (1)
      Loricera larvae (Carabidae) use galeae with an extremely flexible cuticle in
      combination with an adhesive secretion. (2) Adult Stenus species (Staphylinidae)
      employ two highly flexible paraglossae that are covered by an adhesive emulsion
      of lipid droplets dispersed in an aqueous proteinaceous liquid. (3) Springtails
      often adhere to the mouthparts, the antennae, the legs, or other parts of the
      integument of Stenus larvae before being captured with the mandibles.

PMID- 18089021
TI  - Fine structure of adhesive devices of Strepsiptera (Insecta).
AB  - Legs and other body parts of males, females and first instar larvae of almost all
      recognised families of Strepsiptera (Insecta) were examined. Descriptions of
      tibial, tarsal and pretarsal adhesive structures for each family are presented.
      These and attachment devices not associated with the legs are discussed.
      Strepsiptera evolved two strictly different types of tarsal attachment
      structures: hairy surfaces in the males and smooth flexible pads in the first
      instar larvae. Additional adhesive devices are present in several subgroups:
      mushroom-shaped microtrichia on the maxillary palp of males of Bohartillidae and
      acute pointed tibiae, or tarsal segments of males in different families. First
      instar larvae have evolved adhesive hairs on the ventral side of the body and on
      the podomeres. Specialised adhesive hairs are absent in the groundplan of adult
      males of Strepsiptera, but have evolved with the adoption of permanent
      endoparasitism of females. The most elaborate attachment structures, both in
      males and first instar larvae, are present in parasites of fast flying
      hymenopteran hosts (Aculeata).

PMID- 18089022
TI  - Evolution of locomotory attachment pads in the Dermaptera (Insecta).
AB  - This contribution is the first comparative SEM study of tarsal and pretarsal
      structures of 18 dermapteran species, including epizoic Hemimeridae, rare
      Apachyidae, as well as basal Pygidicranidae. Our data reject the apparent
      uniformity of this taxon and show that representatives of Dermaptera have
      independently evolved both types of attachment mechanisms: hairy and smooth.
      Dermaptera possess a wide spectrum of attachment devices: arolia, euplantulae,
      tarsal surfaces covered with specialised tenent setae and other types of
      cuticular outgrowths. The groundpattern of the pretarsal and tarsal attachment
      structures was reconstructed by mapping their characters onto a cladogram,
      generated without tarsal characters. In the groundpattern of recent Dermaptera,
      the tarsus consists of three tarsomeres. Presumably, the last common ancestor of
      the Dermaptera possessed an arolium, since this structure occurs in the most
      basal taxa: Diplatyidae, Karschiellidae (partim, adults), Pygidicranidae partim,
      and Apachyidae. The absence of arolium in two of the pygidicranid taxa is
      probably due to a secondary loss. The arolium seems to be reduced in the 'higher
      Dermaptera' and amongst them, only the Geracinae, which belong to the
      Spongiphoridae and, hence, to the well supported Eudermaptera [European Journal
      of Entomology, 98 (2001), 445], evolved this structure convergently. The
      character state distribution for euplantulae suggests their evolution being
      similar to that of the arolium. All species of Tagalina possess a specialised
      tarsus with a strongly dilated second tarsomere. The same applies to the
      Forficulidae. However, their relatively remote phylogenetic position to Tagalina
      burri is a convincing reason to assume convergent evolution of this character.
      The Chelisochidae, with a slender, elongated second tarsomere, possess a unique
      structure, which supports their monophyly. The special, heart shaped structure of
      the second tarsal segments in the Forficulidae suggests their monophyly. The
      attachment structures of Hemimerus vosseleri are highly derived and probably
      autapomorphic for this taxon.

PMID- 18089023
TI  - Locomotion and adhesion: dynamic control of adhesive surface contact in ants.
AB  - Tarsal adhesive pads of insects are highly dynamic organs that play an important
      role in locomotion. Many insects combine fast running performance with strong
      resistance to detachment forces. This capacity requires an effective control of
      attachment forces at the tarsus and pretarsus. Here we investigate mechanisms of
      attachment control in Asian weaver ants (Oecophylla smaragdina) by measuring the
      dynamics of the adhesive contact area and the claws during locomotion. O.
      smaragdina ants walking upside down on a smooth substrate used only a fraction
      (approx. 14%) of their maximum possible contact area. When these ants were loaded
      with 30 mg weights (corresponding to approx. 6 times their own body weight),
      however, they employed much larger (but still submaximal; approx. 60%) contact
      areas. The increase of contact area was accompanied by a stronger flexion of the
      claws, which demonstrates the participation of the claw flexor muscle in the
      control of adhesive contact. However, only part of the contact area dynamics
      could be explained by the action of the claw flexor. During the stance phase,
      adhesive contact area changed while the claws remained motionless. Even when
      corrected for the effects of claw flexion, adhesive contact areas differed by a
      factor of 2.1 between loaded and unloaded ants. Our findings give evidence that
      running ants control their adhesive contact area by a combination of active
      movements of the claw flexor muscle and passive reactions of the mechanical
      system.

PMID- 18089024
TI  - Structure and mechanics of the tarsal chain in the hornet, Vespa crabro
      (Hymenoptera: Vespidae): implications on the attachment mechanism.
AB  - Two combined mechanisms on the hornet tarsus are adapted to attachment to the
      substrate: a friction-based (claws and spines) and an adhesion-based one
      (arolium). There are two ranges of substrate roughness optimal for attachment,
      either very smooth or very rough. There is an intermediate range of substrate
      grains of small but non-zero size, where both of these mechanisms fail. The
      optimal size of substrate grains for hornet grasping was 50-100 microm. Maximal
      hold to the substrate was achieved when surface irregularities were clamped
      between the claws of opposite legs. In such a position, the insect could
      withstand an external force which was almost 25 times larger than its own weight.
      The tarsal chain is an important part of the entire attachment mechanism. The
      articulations in the kinematic chain of tibia-tarsus-pretarsus are monocondylar.
      Three tarsal muscles and one head of the claw retractor muscle originate in the
      tibia. On pull to the retractor tendon, the tarsus bends in a plane. All elements
      of the tarsal kinematic chain have one active degree of freedom. The distance
      between the intertarsomeric articulation point and the tendon of the claw
      retractor (75-194 microm) corresponds to an efficiency of 1 degrees per 1-3
      mircom of pulling distance travelled by the tendon. The claw turns about 1
      degrees per 4.3-5.0 microm of pulling distance travelled by the unguitractor. The
      arolium turns forward and downward simultaneously with flexion of the claws. The
      kinematic chain of the arolium lacks real condylar joints except the joint at the
      base of the manubrium. Other components are tied by flexible transmissions of the
      membranous cuticle. The walking hornet rests on distal tarsomeres of extended
      tarsi. If the retractor tendon inside the tarsus is fixed, passive extension of
      the tarsomeres might be replaced by claw flexion. Tarsal chain rigidity, measured
      with the force tester, increased when the retractor tendon was tightened.
      Probably, pull to the tendon compresses the tarsomeres, increasing friction
      within contacting areas of rippled surfaces surrounding condyles within
      articulations.

PMID- 18089025
TI  - The effects of plant epicuticular waxy blooms on attachment and effectiveness of
      predatory insects.
AB  - Phytophagous insects and their natural enemies frequently must cling to plants in
      order to forage. Typically, this involves attachment to the layer of lipophilic
      materials, or 'epicuticular waxes' (EW) that covers all primary plant surfaces.
      EW occurring as crystalline waxy 'blooms' can provide a defense against herbivory
      by interfering with attachment to plants by phytophagous insects. On the other
      hand, EW blooms can reduce attachment by predators and parasitoids, potentially
      releasing populations of phytophagous insects from regulation by their natural
      enemies. The net effect of EW blooms on herbivory should therefore vary from
      system to system. When it has been measured, EW bloom typically reduces the
      attachment forces insects can generate on plants. Some herbivores and predators
      preferentially forage on plants with EW blooms. Among these, some appear to have
      physiological or behavioral adaptations that either improve attachment to EW
      blooms or cope with reduced attachment to plants surfaces bearing EW blooms. How
      EW blooms disrupt insect attachment and how insects potentially overcome this
      challenge has not been determined. Some hypotheses are offered in this review.
      Their elucidation may help understand the mechanics of attachment to plants, with
      applications including helping to improve biological control of some insect
      pests.

PMID- 18089026
TI  - How do plant waxes cause flies to slide? Experimental tests of wax-based trapping
      mechanisms in three pitfall carnivorous plants.
AB  - The waxy surfaces of three carnivorous plants, Nepenthes ventrata (Nepenthaceae),
      Brocchinia reducta and Catopsis berteroniana (Bromeliaceae), were compared using
      scanning electron microscopy (SEM). Their effects on attachment and locomotion of
      the fly Calliphora vomitoria were studied. The waxy surface of N. ventrata is
      comprised of a heterogeneous layer from which only platelet-shaped crystalloids
      could be detached by brushing. In the two bromeliads, the crystalloids are thread
      shaped and form a homogenous dense network, which was entirely removable from the
      epidermis. Experimental data showed that none of the flies was able to walk
      across any of the waxy surfaces and only a few were able to take off from those
      surfaces. Both the absence of sites for claw anchorage, especially in N.
      ventrata, and the wax itself were shown to contribute to the trapping ability of
      the plants. Only half of the flies quickly recovered their locomotion ability on
      a glass surface after 20 min of being tested on waxy plant surfaces. SEM
      observations revealed that the wax of C. berteroniana formed a powder of broken
      crystals on the tenent setae of the flies' pulvilli. In contrast, the waxes of B.
      reducta and N. ventrata appeared to have lost their crystal structure in contact
      with the tenent setae and formed an amorphous substance that adhered setae
      together. We hypothesize that wax interacts with adhesive fluids secreted by the
      fly pad and thereby prevents the tenent setae from functioning effectively.

PMID- 18089027
TI  - Loss of escape responses and giant neurons in the tailflipping circuits of
      slipper lobsters, Ibacus spp. (Decapoda, Palinura, Scyllaridae).
AB  - In many decapod crustaceans, escape tailflips are triggered by lateral giant (LG)
      and medial giant (MG) interneurons, which connect to motor giant (MoG) abdominal
      flexor neurons. Several decapods have lost some or all of these giant neurons,
      however. Because escape-related giant neurons have not been documented in
      palinurans, I examined tailflipping and abdominal nerve cords for giant neurons
      in two scyllarid lobster species, Ibacus peronii and Ibacus alticrenatus. Unlike
      decapods with giant neurons, Ibacus do not tailflip in response to sudden taps.
      Ibacus can perform non-giant tailflipping: the frequency of tailflips during
      swimming is adjusted by altering the gap between each individual tailflip.
      Abdominal nerve cord sections show no LG or MG interneurons. Backfilling nerve 3
      of abdominal ganglia revealed no MoG neurons, and the fast flexor motor neuron
      population is otherwise identical to that described for crayfish. The loss of
      giant neurons in Ibacus represents an independent deletion of these cells
      compared to other reptantian decapods known to have lost these giant neurons.
      This loss is correlated with the normal posture in scyllarids, in which the last
      two abdominal segments are flexed, and an alternative defensive strategy,
      concealment by digging into sand.

PMID- 18089028
TI  - Ontogeny of identified cells from the median domain in the embryonic brain of the
      grasshopper Schistocerca gregaria.
AB  - In this paper, we propose an ontogeny for previously identified cells from the
      median domain in the midline of the embryonic brain of the grasshopper
      Schistocerca gregaria. The so-called lateral cells (LCs) are characteristically
      located laterally within the median domain at its border with the protocerebral
      hemispheres. The LC occurs singly and can be identified in the early embryo on
      the basis of their expression of the cell surface lipocalin Lazarillo. Using
      immunocytochemical, dye injection, electron microscopical and histological
      methods, we show that these LC are neurons and derive as postmitotic cells
      directly from the epithelium of the median domain. Further, they and the other
      identified cells of the median domain such as the protocerebral commissure
      pioneers (PCP), co-express the Mes-3 antigen, consistent with a derivation from
      the mesectodermal germ layer of the embryo. Subsequent to axogenesis, electron
      microscopy reveals that these Mes-3-expressing LC fasciculate with the co
      expressing PCPs within the developing protocerebral commissure. We present a
      model for the origin of all these cells based on histological data and
      bromodeoxyuridine incorporation. The model suggests a delamination of cells from
      the mesectoderm followed by a migration to their ultimate sites within the median
      domain.

PMID- 18089029
TI  - Occurrence of midgut perimicrovillar membranes in paraneopteran insect orders
      with comments on their function and evolutionary significance.
AB  - Hemipterans are characterized by the absence of the peritrophic membrane, an
      anatomical structure that envelopes the food bolus in the majority of insects.
      However, the microvillar membranes of many hemipteran midgut cells are not in
      direct contact with the food bolus, due to the existence of the so-called
      perimicrovillar membrane (PMM), which covers the microvilli extending into the
      gut lumen with dead ends. alpha-Glucosidase is a biochemical marker for PMM in
      the seed sucker bug Dysdercus peruvianus (Heteroptera: Pyrrhocoridae). In this
      article, we report that adults of the major hemipteran infra-orders
      (Sternorrhyncha, Auchenorrhyncha, and Heteroptera) have PMM and a major membrane
      bound alpha-glucosidase, which has properties similar to those of the D.
      peruvianus enzyme. A polyclonal antibody raised against the enzyme of D.
      peruvianus recognized the enzymes present in PMM from the above-mentioned
      hemipteran groups. The same antibody was also able of recognizing perimicrovillar
      alpha-glucosidase from thrips. No PMM nor membrane-bound alpha-glucosidase were
      found in Psocoptera and Phthiraptera midguts. This suggests that PMM and PMM
      bound-alpha-glucosidase are widespread among insects of the order Hemiptera and
      of the sister order Thysanoptera. The data support the hypothesis that PMM may
      have originated in the Condylognatha (Paraneopteran taxon including Hemiptera and
      Thysanoptera) ancestral stock and are associated with plant sap feeding.

PMID- 18089030
TI  - The fine structure of the coxal glands in Myobia murismusculi (Schrank) (Acari:
      Myobiidae).
AB  - The coxal glands of M. murismusculi consist of the proximal tubular portion
      (tubulus), the distal glandular sac and the terminal excretory duct. The tubulus
      comprises looped proximal and distal tubes that run in close association with
      each other. The cells of the proximal tube form numerous short protrusions that
      project into the neighbouring organs through the pores in their basal lamina. The
      sac is a distal part of the gland and so it cannot be considered as a homologue
      of the proximal filter sacculus of other arthropods. A large number of
      pinocytotic vesicles and lysosome-like bodies in the epithelial lining of the sac
      imply that the main functions of this organ may be the absorption of substances
      from the lumen of the gland and their subsequent intracellular transformation. In
      addition the sac of females was shown to produce dense secretory granules. The
      ultrastructural features of the glands are discussed and compared to other
      representatives of Acari.

PMID- 18089031
TI  - Oogenesis in phthirapterans (Insecta: Phthiraptera). I. Morphological and
      histochemical characterization of the oocyte nucleus and its inclusions.
AB  - We characterize morphological and histochemical changes occurring within the
      oocyte nucleus (germinal vesicle) during oogenesis in two phthirapteran species:
      the pig louse, Haematopinus suis (Anoplura) and the pigeon louse, Columbicola
      columbae (Mallophaga). In previtellogenic oocytes, within the oocyte nucleus the
      chromatin condenses and forms the karyosome. In contact with the karyosome
      numerous dense and highly heterogeneous nuclear bodies occur. We demonstrate that
      these nuclear inclusions have complex structure and contain RNA and argyrophilic
      proteins of nucleolar organizer (Ag-NOR proteins). Results of immunogold electron
      microscopy experiments are also presented. The obtained results suggest that the
      phthirapteran nuclear bodies are assemblages of ribonucleoproteins that are
      stored in the oocyte nucleus and might be utilized during early stages of
      embryonic development. In the investigated species, the nuclear envelope of the
      germinal vesicle is equipped with characteristic protrusions. Ultrastructural
      analysis revealed striking similarity of these structures to the initial stages
      of the formation of accessory nuclei. Based on these results, we speculate on the
      possible evolutionary origin of the accessory nuclei in phthirapterans.

PMID- 18089032
TI  - On the occurrence of coenospermia in mesothelid spiders (Araneae: Heptathelidae).
AB  - Two species of the early derivative spider family Heptathelidae (Heptathela
      kimurai yanbaruensis and Ryuthela nishihirai nishihirai) have been investigated
      with respect to spermiogenesis, focussing on late events during which peculiar
      transfer forms are developed. It is shown, for the first time in detail, that
      these spiders produce coenospermia. The coenospermia of these species are large
      aggregates containing more than 20 individual encapsulated spermatozoa. The
      coenospermia possess a likely flexible envelope formed by a thick multilayered
      secretion, which protects the spermatozoa during transfer to the female genital
      system and storage in the receptacula. In addition, a short description of the
      main cell components of the individual spermatozoa is given as a complement to
      previous studies. With the observation presented here, the suggestion that
      coenospermia are an ancestral character in the Araneae is further confirmed, and
      plesiomorphic features of spider sperms are consolidated.

PMID- 18089033
TI  - Arthropod locomotion systems: from biological materials and systems to robotics.
      Introduction.

PMID- 18089034
TI  - Design and mechanical properties of insect cuticle.
AB  - Since nearly all adult insects fly, the cuticle has to provide a very efficient
      and lightweight skeleton. Information is available about the mechanical
      properties of cuticle-Young's modulus of resilin is about 1 MPa, of soft cuticles
      about 1 kPa to 50 MPa, of sclerotised cuticles 1-20 GPa; Vicker's Hardness of
      sclerotised cuticle ranges between 25 and 80 kgf mm(-2); density is 1-1.3 kg m(
      3)-and one of its components, chitin nanofibres, the Young's modulus of which is
      more than 150 GPa. Experiments based on fracture mechanics have not been
      performed although the layered structure probably provides some toughening. The
      structural performance of wings and legs has been measured, but our understanding
      of the importance of buckling is lacking: it can stiffen the structure (by
      elastic postbuckling in wings, for example) or be a failure mode. We know nothing
      of fatigue properties (yet, for instance, the insect wing must undergo millions
      of cycles, flexing or buckling on each cycle). The remarkable mechanical
      performance and efficiency of cuticle can be analysed and compared with those of
      other materials using material property charts and material indices. Presented in
      this paper are four: Young's modulus-density (stiffness per unit weight),
      specific Young's modulus-specific strength (elastic hinges, elastic energy
      storage per unit weight), toughness-Young's modulus (fracture resistance under
      various loading conditions), and hardness (wear resistance). In conjunction with
      a structural analysis of cuticle these charts help to understand the relevance of
      microstructure (fibre orientation effects in tendons, joints and sense organs,
      for example) and shape (including surface structure) of this fibrous composite
      for a given function. With modern techniques for analysis of structure and
      material, and emphasis on nanocomposites and self-assembly, insect cuticle should
      be the archetype for composites at all levels of scale.

PMID- 18089035
TI  - The jumping mechanism of cicada Cercopis vulnerata (Auchenorrhyncha, Cercopidae):
      skeleton-muscle organisation, frictional surfaces, and inverse-kinematic model of
      leg movements.
AB  - In Auchenorrhyncha, jumping is achieved by metathoracic muscles which are
      inserted into the trochanter of the hind leg. The synchronisation of movements of
      the hind legs is a difficult problem, as the leg extension that produces the jump
      occurs in less than 1 ms. Even slight asynchrony could potentially result in
      failure of a jump. Both the synchronisation of the movements of a pair of jumping
      legs, and their stabilisation during a jump, seem to be important problems for
      small jumping insects. The present study was performed in order to clarify some
      questions of the functional morphology of the leafhopper jumping mechanism. It is
      based on skeleton-muscle reconstruction, high-speed video recordings,
      transmission (TEM) and scanning electron microscopic (SEM) investigations of the
      cuticle, together with 3D inverse-kinematic modelling of angles and working zones
      of hind leg joints of cicada Cercopis vulnerata (Cercopidae). The complete
      extension of the hind leg takes less than 1 ms, which suggests that the jump is
      powered not only by the muscle system, but also by an elastic spring.
      Histological staining and fluorescence microscopy showed resilin-bearing
      structures, responsible for elastic energy storage, in the pleural area of the
      metathorax. Synchronisation of hind leg movements may be aided by microtrichia
      fields that are located on the medial surface of each hind coxa. In
      Auchenorrhyncha, hind coxae are rounded in their anterior and lateral parts,
      whereas medial parts are planar, and contact each other over a rather large area.
      The inverse-kinematic model of propulsive leg movements was used to draw the
      surface outlined by the medial surface of the coxa, during the jump movement.
      This is a cone surface, faced with its bulged-in side, medially. Surfaces
      outlined by the movements of both right and left coxae overlap in their anterior
      and posterior positions. In both extreme positions, coxae are presumably
      connected to each other by coupled microtrichia fields. Thus, in extreme
      positions, both coxae can be moved synchronously.

PMID- 18089036
TI  - Righting kinematics in beetles (Insecta: Coleoptera).
AB  - Twenty modes of stereotyped righting motions were observed in 116 representative
      species of coleoptera. Methods included cine and stereocine recording with
      further frame by frame analysis, stereogrammetry, inverse kinematic
      reconstruction of joint angles, stroboscopic photography, recording of
      electromyograms, 3D measurements of the articulations, etc. The basic mode
      consists of a search phase, ending up with grasping the substrate, and a
      righting, overturning phase. Leg coordination within the search cycle differs
      from the walking cycle with respect to phasing of certain muscle groups. Search
      movements of all legs appear chaotic, but the tendency to move in antiphase is
      still present in adjacent ipsilateral and contralateral leg pairs. The system of
      leg coordination might be split: legs of one side might search, while
      contralateral legs walk, or fore and middle legs walk while hind legs search.
      Elaborated types of righting include somersaults with the aid of contralateral or
      diagonal legs, pitch on elytra, jumps with previous energy storage with the aid
      of unbending between thoracic segments (well-known for Elateridae), or quick
      folding of elytra (originally described in Histeridae). Righting in beetles is
      compared with righting modes known in locusts and cockroaches. Search in a
      righting beetle is directed dorsad, while a walking insect searches for the
      ground downwards. Main righting modes were schematized for possible application
      to robotics.

PMID- 18089037
TI  - Behaviour-based modelling of hexapod locomotion: linking biology and technical
      application.
AB  - Walking in insects and most six-legged robots requires simultaneous control of up
      to 18 joints. Moreover, the number of joints that are mechanically coupled via
      body and ground varies from one moment to the next, and external conditions such
      as friction, compliance and slope of the substrate are often unpredictable. Thus,
      walking behaviour requires adaptive, context-dependent control of many degrees of
      freedom. As a consequence, modelling legged locomotion addresses many aspects of
      any motor behaviour in general. Based on results from behavioural experiments on
      arthropods, we describe a kinematic model of hexapod walking: the distributed
      artificial neural network controller walknet. Conceptually, the model addresses
      three basic problems in legged locomotion. (I) First, coordination of several
      legs requires coupling between the step cycles of adjacent legs, optimising
      synergistic propulsion, but ensuring stability through flexible adjustment to
      external disturbances. A set of behaviourally derived leg coordination rules can
      account for decentralised generation of different gaits, and allows stable
      walking of the insect model as well as of a number of legged robots. (II) Second,
      a wide range of different leg movements must be possible, e.g. to search for
      foothold, grasp for objects or groom the body surface. We present a simple neural
      network controller that can simulate targeted swing trajectories, obstacle
      avoidance reflexes and cyclic searching-movements. (III) Third, control of
      mechanically coupled joints of the legs in stance is achieved by exploiting the
      physical interactions between body, legs and substrate. A local positive
      displacement feedback, acting on individual leg joints, transforms passive
      displacement of a joint into active movement, generating synergistic assistance
      reflexes in all mechanically coupled joints.

PMID- 18089038
TI  - Mechanical aspects of legged locomotion control.
AB  - We review the mechanical components of an approach to motion science that enlists
      recent progress in neurophysiology, biomechanics, control systems engineering,
      and non-linear dynamical systems to explore the integration of muscular,
      skeletal, and neural mechanics that creates effective locomotor behavior. We use
      rapid arthropod terrestrial locomotion as the model system because of the wealth
      of experimental data available. With this foundation, we list a set of hypotheses
      for the control of movement, outline their mathematical underpinning and show how
      they have inspired the design of the hexapedal robot, RHex.

PMID- 18089039
TI  - Load sensing and control of posture and locomotion.
AB  - This article reviews recent findings on how forces are detected by sense organs
      of insect legs and how this information is integrated in control of posture and
      walking. These experiments have focused upon campaniform sensilla, receptors that
      detect forces as strains in the exoskeleton, and include studies of sensory
      discharges in freely moving animals and intracellular characterization of
      connectivity of afferent inputs in the central nervous system. These findings
      provide insights into how campaniform sensilla can contribute to the adjustment
      of motor outputs to changes in load. In this review we discuss (1) anatomy of the
      receptors and their activities in freely moving insects, (2) mechanisms by which
      inputs are incorporated into motor outputs and (3) the integration of sensory
      signals of diverse modalities. The discharges of some groups of receptors can
      encode body load when standing. Responses are also correlated with muscle
      generated forces during specific times in walking. These activities can enhance
      motor outputs through reflexes and can affect the timing of motoneuron firing
      through inputs to pattern generating interneurons. Flexibility in the system is
      also provided by interactions of afferent inputs at several levels. These
      mechanisms can contribute to the adaptability of insect locomotion to diverse
      terrains and environments.

PMID- 18089040
TI  - Dynamic simulation of insect walking.
AB  - Insect walking relies on a complex interaction between the environment, body
      segments, muscles and the nervous system. For the stick insect in particular,
      previous investigations have highlighted the role of specific sensory signals in
      the timing of activity of central neural networks driving the individual leg
      joints. The objective of the current study was to relate specific sensory and
      neuronal mechanisms, known from experiments on reduced preparations, to the
      generation of the natural sequence of events forming the step cycle in a single
      leg. We have done this by simulating a dynamic 3D-biomechanical model of the
      stick insect coupled to a reduced model of the neural control system,
      incorporating only the mechanisms under study. The neural system sends muscle
      activation levels to the biomechanical system, which in turn provides correctly
      timed propriosensory signals back to the neural model. The first simulations were
      designed to test if the currently known mechanisms would be sufficient to explain
      the coordinated activation of the different leg muscles in the middle leg. Two
      experimental situations were mimicked: restricted stepping where only the coxa
      trochanteral joint and the femur-tibia joint were free to move, and the
      unrestricted single leg movements on a friction-free surface. The first of these
      experimental situations is in fact similar to the preparation used in gathering
      much of the detailed knowledge on sensory and neuronal mechanisms. The
      simulations show that the mechanisms included can indeed account for the entire
      step cycle in both situations. The second aim was to test to what extent the same
      sensory and neuronal mechanisms would be adequate also for controlling the front
      and hind legs, despite the large differences in both leg morphology and kinematic
      patterns. The simulations show that front leg stepping can be generated by
      basically the same mechanisms while the hind leg control requires some
      reorganization. The simulations suggest that the influence from the femoral
      chordotonal organs on the network controlling levation-depression may have a
      reversed effect in the hind legs as compared to the middle and front legs. This,
      and other predictions from the model will have to be confirmed by additional
      experiments.

PMID- 18089041
TI  - Sensorimotor control of navigation in arthropod and artificial systems.
AB  - Arthropods exhibit highly efficient solutions to sensorimotor navigation
      problems. They thus provide a source of inspiration and ideas to robotics
      researchers. At the same time, attempting to re-engineer these mechanisms in
      robot hardware and software provides useful insights into how the natural systems
      might work. This paper reviews three examples of arthropod sensorimotor control
      systems that have been implemented and tested on robots. First we discuss visual
      control mechanisms of flies, such as the optomotor reflex and collision
      avoidance, that have been replicated in analog VLSI (very large scale
      integration) hardware and used to produce corrective behavior in robot vehicles.
      Then, we present a robot model of auditory localization in the cricket; and
      discuss integration of this behavior with the optomotor behavior previously
      described. Finally we present a model of olfactory search in the moth, which
      makes use of several sensory cues, and has also been tested using robot hardware.
      We discuss some of the similarities and differences of the solutions obtained.

PMID- 18089042
TI  - Aerial locomotion in flies and robots: kinematic control and aerodynamics of
      oscillating wings.
AB  - Flight in flies results from a feedback cascade in which the animal converts
      mechanical power produced by the flight musculature into aerodynamic forces. A
      major goal of flight research is to understand the functional significance of the
      various components in this cascade ranging from the generation of the neural
      code, the control of muscle mechanical power output, wing kinematics and unsteady
      aerodynamic mechanisms. Here, I attempted to draw a broad outline on fluid
      dynamic mechanisms found in flapping insect wings such as leading edge vorticity,
      rotational circulation and wake capture momentum transfer, as well as on the
      constraints of flight force control by the neuromuscular system of the fruit fly
      Drosophila. This system-level perspective on muscle control and aerodynamic
      mechanisms is thought to be a fundamental bridge in any attempt to link the
      function and performance of the various flight components with their particular
      role for wing motion and aerodynamic control in the behaving animal. Eventually,
      this research might facilitate the development of man-made biomimetic autonomous
      micro air vehicles using flapping wing motion for propulsion that are currently
      under construction by engineers.

PMID- 18089043
TI  - Underwater walking.
AB  - Lobsters are generalist decapods that evolved in a broad variety of niches in the
      Northwestern Atlantic. Due to their inherent buoyancy they have acquired
      adaptations to reduced traction and surge. We have developed a biomimetic robot
      based on the lobster that features artificial muscle actuators and sensors
      employing labeled-line codes. The central controller for this robot is based on
      the command neuron, coordinating neuron central pattern generator model. A
      library of commands is released by sensor feedback to mediate adaptive sequences
      and goal achieving behavior. Rheotaxic behaviors can mediate adaptations to
      achieve some of the advantages of the biological models.

PMID- 18089044
TI  - Convergent evolution and locomotion through complex terrain by insects,
      vertebrates and robots.
AB  - Arthropods are the most successful members of the animal kingdom largely because
      of their ability to move efficiently through a range of environments. Their
      agility has not been lost on engineers seeking to design agile legged robots.
      However, one cannot simply copy mechanical and neural control systems from
      insects into robotic designs. Rather one has to select the properties that are
      critical for specific behaviors that the engineer wants to capture in a
      particular robot. Convergent evolution provides an important clue to the
      properties of legged locomotion that are critical for success. Arthropods and
      vertebrates evolved legged locomotion independently. Nevertheless, many neural
      control properties and mechanical schemes are remarkably similar. Here we
      describe three aspects of legged locomotion that are found in both insects and
      vertebrates and that provide enhancements to legged robots. They are leg
      specialization, body flexion and the development of a complex head structure.
      Although these properties are commonly seen in legged animals, most robotic
      vehicles have similar legs throughout, rigid bodies and rudimentary sensors on
      what would be considered the head region. We describe these convergent properties
      in the context of robots that we developed to capture the agility of insects in
      moving through complex terrain.

PMID- 18089045
TI  - Embryonic development of the sensory innervation of the antenna of the
      grasshopper Schistocerca gregaria.
AB  - The establishment of the sensory nervous system of the antenna of the grasshopper
      Schistocerca gregaria was examined using immunocytochemical methods and in the
      light of the appendicular and articulated nature of this structure. The former is
      demonstrated first by the expression pattern of the segment polarity gene
      engrailed in the head neuromere innervating the antenna, the deutocerebrum.
      Engrailed expression is present in identified deutocerebral neuroblasts and, as
      elsewhere in the body, is continuous with cells of the posterior epithelium of
      the associated appendage, in this case the antenna. Second, early expression of
      the glial homeobox gene reversed polarity (repo) in the antenna is by a
      stereotypic pair of cells at the antenna base, a pattern we show is repeated
      metamerically for each thoracic appendage of the embryo. Subsequently, three
      regions of Repo expression (A1, A2, A3) are seen within the antenna, and may
      represent a preliminary form of articulation. Bromodeoxyuridine incorporation
      reveals that these regions are sites of intense cell differentiation. Neuron
      specific horseradish peroxidase and Lazarillo expression confirm that the
      pioneers of the ventral and dorsal tracts of the antennal sensory nervous system
      are amongst these differentiating cells. Sets of pioneers appear simultaneously
      in several bands and project confluent axons towards the antennal base. We
      conclude that the sensory nervous system of the antenna is not pioneered from the
      tip of the antenna alone, but in a stepwise manner by cells from several zones.
      The early sensory nervous systems of antenna, maxilla and leg therefore follow a
      similar developmental program consistent with their serially homologous nature.

PMID- 18089046
TI  - Ultrastructural cytochemistry of the sex pheromone glands of Lutzomyia cruzi male
      sand flies (Diptera: Psychodidae: Phlebotominae).
AB  - The sex pheromone glands of Lutzomyia cruzi male sand flies (Diptera:
      Psychodidae) were analyzed by cytochemical techniques. In adult males, the
      epithelium at the fourth abdominal tergite is modified into a glandular
      epithelium, with large columnar gland cells located side by side. The gland cell
      cytoplasm contains a large number of mitochondria and peroxisomes, the latter
      with positive (electron-dense) reaction for catalase, a typical peroxisomal
      enzyme marker. The gland cell cytoplasm also contains a central vacuolated area,
      with a large number of electron-lucent vacuoles, not limited by a unit membrane.
      In well-preserved preparations such vacuoles present a homogenous and slightly
      electron-dense content, typical of lipid droplets. Indeed, incubation of the
      tergites with imidazole-buffered osmium tetroxide (to detect lipids) resulted in
      positive reaction in these vacuoles, as well as in between the microvilli of the
      gland cells. Use of the osmium-potassium iodide (Os-KI) technique allowed to
      demonstrate the presence of several endoplasmic reticulum (ER) profiles, as
      expected in secretory cells. Our data suggest that ER, lipid droplets and
      peroxisomes are involved in the sand fly pheromone biosynthesis.

PMID- 18089047
TI  - Post-embryonic photoreceptor development and dark/light adaptation in the spittle
      bug Philaenus spumarius (L.) (Homoptera, Cercopidae).
AB  - The aims of this paper have been to describe (1) the general structure of the
      compound eye of the spittle bug Philaenus spumarius, (2) the eye's post-embryonic
      development, (3) photomechanical changes upon dark/light adaptation in the eye,
      and (4) how leaving the semi-aquatic foam bubble and turning into an adult
      affects the organization of the eye. Spittle bugs, irrespective of size or sex,
      possess apposition type compound eyes. The eye's major components (i.e. facet,
      cornea, cone and rhabdom) grow rather isometrically from the smallest nymph to
      the adult. Photomechanical changes can occur during both nymphal and adult phases
      and manifest themselves through pigment granules and mitochondria migrating to
      and away from the rhabdom, and rhabdom diameters varying with time of day and
      ambient light level. When a nymph transforms into an adult, its compound eyes'
      dorsoventral axes widen, facet diameters increase, facet shapes turn from
      circular to pentagonal and hexagonal, the cornea thickens and the rhabdoms become
      thinner. The agile adults, free from the foam that surrounds the nymphs, can be
      expected to need their vision more than the nymphs, and the changes in eye
      structure do, indeed, indicate that the adults have superior visual acuity. A
      thicker cornea in the adults reduces water loss and protects the compound eye
      from mechanical and light-induced damage: protection given to the nymphs by their
      foam bubbles.

PMID- 18089048
TI  - Variation in number and differentiation of the abdominal infrared receptors in
      the Australian 'fire-beetle' Merimna atrata (Coleoptera, Buprestidae).
AB  - Most individuals of the Australian 'fire-beetle' Merimna atrata have two pairs of
      IR receptors which are located ventrolaterally on the second and third abdominal
      sternite. An IR receptor consists of a specialized IR absorbing area, which is
      innervated by a neural complex. This complex contains one thermoreceptive
      multipolar neuron with a unique terminal dendritic mass (TDM) and two scolopidia
      and was termed 'sensory complex'. However, also individuals with one pair of IR
      receptors on the second sternite and beetles with three pairs on the second,
      third, and fourth sternites were found. Additionally, beetles having one or two
      pairs of IR receptors may have preliminary stages of IR receptors on the third
      and fourth sternite, respectively. We found two kinds of preliminary stages, both
      of which are characterized by a much less pronounced absorbing area. In all five
      abdominal sternites segmental nerves are attached to the cuticle with a neural
      complex. Investigation of complexes of non-IR sternites suggests that the sensory
      cells inside the sensory complex of an IR receptor have developed from common
      internal stretch receptors. From our results it can be hypothesized that the IR
      sensory system in Merimna atrata has not yet reached a stage, which can be
      regarded as evolutionary stable.

PMID- 18089049
TI  - The initial stages of oogenesis and their relation to differential fertility in
      the honey bee (Apis mellifera) castes.
AB  - Neither the overall differences in ovariole number nor the caste-specifically
      modulated expression of vitellogenin can fully explain the striking caste
      differences in honey bee reproduction, in particular the mechanisms that block
      oogenesis in virgin queens and in workers kept in the presence of a queen. For
      this reason we investigated the initial stages of oogenesis in queens in relation
      to mating status and in workers exposed to different social conditions. A
      striking feature in ovarioles of both castes was a considerably elongated
      terminal filament which consisted not only of normal terminal filament cells but
      also contained apparently undifferentiated cells that were tentatively considered
      as stem cells. BrdU incorporation was detected in the upper germarium, as well as
      in the terminal filament. Cytoskeleton analysis by TRITC-phalloidin labeling for
      F-actin, and immunofluorescence detection for beta-tubulin did not reveal
      structural differences in the early oogenesis steps between queens and queenless
      workers. In contrast, queenright workers showed signs of a disorganized
      microtubule and microfilament system that could explain the histological evidence
      for progressive cell death observed in the germaria. In addition to cytoplasmic
      tubulin we also detected marked intranuclear foci indicating the presence of
      nuclear beta(II)-tubulin.

PMID- 18089050
TI  - Interspecific morphological variation in the wood-feeding cockroach, Cryptocercus
      (Dictyoptera: Cryptocercidae).
AB  - Appalachian species of Cryptocercus (Dictyoptera: Cryptocercidae) display
      considerable genetic variation, but little morphological variation has been
      reported. We employed light and scanning electron microscopy to investigate
      variation in male and female reproductive structures among four species of
      Cryptocercus. Our results indicated consistent, species-specific differences
      exist in the genitalia of the four species. Males exhibit moderate interspecific
      differences in the shape of the subgenital plate and third left phallomere hook.
      Females display consistent interspecific differences in the size of setae on the
      basivalvula and great differences in size, number, and pattern of setae on the
      base of the second valves. Together, the interspecific variation in female
      reproductive structures can be used to identify each of the four Cryptocercus
      species that occur in the Appalachian Mountains.

PMID- 18089051
TI  - Larval development of Japanese 'conchostracans': part 2, larval development of
      Caenestheriella gifuensis (Crustacea, Branchiopoda, Spinicaudata, Cyzicidae),
      with notes on homologies and evolution of certain naupliar appendages within the
      Branchiopoda.
AB  - As part of a larger project examining and comparing the ontogeny of all major
      taxa of the Branchiopoda in a phylogenetic context, the larval development of
      Caenestheriella gifuensis (Ishikawa, 1895), a Japanese spinicaudatan
      'conchostracan', is described by scanning electron microscopy. Seven different
      larval stages are recognised, in most cases based on significant morphological
      differences. They range in length from about 200 to 850mum. Nauplius 1 has a
      plumb and lecithotrophic appearance with a rounded hind body and a labrum with an
      incipient medial spine. Limb segmentation is mostly unclear but the second
      antennae have more putative segments delineated than are expressed in the later
      stages. Feeding structures such as the mandibular coxal process and antennal
      coxal spine are only weakly developed. Nauplius 2 is very different from nauplius
      1 and has three large spines on the labral margin and two long caudal spines.
      Feeding structures such as the mandibular coxal process and various spines and
      setae are developed, but whether feeding begins at this stage was not determined.
      The mandible has developed an 'extra' seta on endopod segment 1, absent in
      Nauplius 1. The segmentation of the second antenna has changed significantly due
      to fusions of various early segments. Nauplius 3 is like nauplius 2 in
      morphological detail, but larger and more elongate. Nauplius 4 has developed a
      pair of small anlagen of the carapace and rudiments of the first five pairs of
      trunk limbs, and the coxal spine of the antenna has become distally bifid.
      Nauplius 5 has a larger carapace anlage, externally visible enditic portions of
      the elongate trunk limbs, and a pair of primordial dorsal telson setae. Nauplius
      6 has a larger and partly free carapace and better-developed, partly free trunk
      limbs with incipient enditic, endopodal, and exopodal setation. A pair of caudal
      spines, dorsal to the large caudal spines, has appeared. Nauplius 7 is quite
      similar to nauplius 6 but is larger and has slightly longer caudal and labral
      spines; also, the setation of the most anterior trunks limbs is better developed.
      The larval development is largely similar to that of other spinicaudatans. The
      larval mandible, which is evolutionarily conservative within the Branchiopoda,
      reveals a setation pattern similar to that of the Anostraca and Notostraca (two
      setae on mandibular endopod segment 1). Most other spinicaudatans and all
      examined laevicaudatans share another setal pattern (one seta on mandibular
      endopod segment 1), which could indicate a close relationship among these taxa.
      The second antenna undergoes a special development, which provides an insight
      into the evolution of this limb within the Branchiopoda. In nauplius 1 the
      basipod, endopod, and exopod are all superficially divided into a relatively high
      number of segments. In later nauplii some of these have fused, forming fewer but
      larger segments. We suggest that this ontogeny reflects the evolution of antennae
      in the conchostracans. Various aspects of the morphology of the antennae are
      discussed as possible synapormorphies for either the Diplostraca or subgroups of
      the Conchostraca.

PMID- 18089052
TI  - Morphology of a novel glandular epithelium lining the infrabuccal cavity in the
      ant Monomorium pharaonis (Hymenoptera, Formicidae).
AB  - A novel glandular epithelium lining the infrabuccal cavity and anterior pharynx
      is described in both workers and queens of the pharaoh's ant Monomorium
      pharaonis. The infrabuccal cavity, connected with the buccal tube, forms a
      ventral outgrowth of the anterior pharynx, and as such displays the tegumental
      lining with a cuticle and an epithelial layer. In its dorsal region, the cavity's
      epithelium reaches a thickness of approx. 11-12mum in both workers and queens,
      which is considerably thicker than the epithelium lining the rest of the
      infrabuccal cavity. Also the possible role of the infrabuccal gland is discussed.

PMID- 18089054
TI  - Structure and ultrastructure of the silk glands and spinneret of Helicoverpa
      armigera (Hubner) (Lepidoptera: Noctuidae).
AB  - This study provides comprehensive documentation of silk production in the pest
      moth Helicoverpa armigera from gland secretion to extrusion of silk thread. The
      structure of the silk glands, accessory structures and extrusion apparatus are
      reported. The general schema of the paired silk glands follows that found for
      Lepidoptera. Morphology of the duct, silk press, muscle attachments and spigot
      are presented as a three-dimensional reconstruction and the cuticular crescent
      shaped profile of the silk press is demonstrated in both open and closed forms
      with attendant muscle blocks, allowing advances in our knowledge of how the silk
      press functions to regulate the extrusion of silk. Growth of the spigot across
      instars is documented showing a distinctive developmental pattern for this
      extrusion device. Its shape and structure are related to use and load-bearing
      activity.

PMID- 18089055
TI  - Neuroanatomy of the sucking pump of the moth, Manduca sexta (Sphingidae,
      Lepidoptera).
AB  - Knowledge of the neuroanatomy of the sucking pump of Manduca sexta (Sphingidae)
      is valuable for studies of olfactory learning, pattern generators, and
      postembryonic modification of motor circuitry. The pump comprises a cibarial
      valve, a buccal pump, and an esophageal sphincter valve. Cibarial opener and
      closer muscles control the cibarial valve. Six pairs of dilator muscles and a
      compressor muscle operate the buccal pump. The cibarial opener and one pair of
      buccal dilator muscles are innervated by paired neurons in the tritocerebrum, and
      the cibarial opener has double, bilateral innervation. Their tritocerebral
      innervation indicates that these muscles evolved from labro-clypeal muscles. The
      remaining paired buccal dilator muscles each are innervated by an unpaired motor
      neuron in the frontal ganglion. These motor neurons project bilaterally through
      the frontal connectives to dendritic arborizations in the tritocerebrum. These
      projections also have a series of dendritic-like arborizations in the
      connectives. The cibarial closer and buccal compressor muscles are also
      innervated by motor neurons in the frontal ganglion, but only the closer muscle
      neuron projects bilaterally to the tritocerebrum. The innervation of the pump
      muscles indicates that they are associated with the stomodaeum, and, therefore,
      the buccal pump evolved from the anterior stomodaeum rather than from the
      cibarium.

PMID- 18089056
TI  - A confined taste area in a lepidopteran brain.
AB  - Knowledge about the neuronal pathways of the taste system is interesting both for
      studying taste coding and appetitive learning of odours. We here present the
      morphology of the sensilla styloconica on the proboscis of the moth Heliothis
      virescens and the projections of the associated receptor neurones in the central
      nervous system. The morphology of the sensilla was studied by light microscopy
      and by scanning- and transmission electron microscopy. Each sensillum contains
      three or four sensory neurones; one mechanosensory and two or three chemosensory.
      The receptor neurones were stained with neurobiotin tracer combined with avidin
      fluorescein conjugate, and the projections were viewed in a confocal laser
      scanning microscope. The stained axons entered the suboesophageal ganglion via
      the maxillary nerves and were divided into two categories based on their
      projection pattern. Category one projected exclusively ipsilaterally in the
      dorsal suboesophageal ganglion/tritocerebrum and category two projected
      bilaterally and more ventrally in the suboesophageal ganglion confined to the
      anterior surface of the neuropil. The bilateral projecting neurones had one
      additional branch terminating ipsilaterally in the dorsal suboesophageal
      ganglion/tritocerebrum. A possible segregation of the two categories of
      projections as taste and mechanosensory is discussed.

PMID- 18089057
TI  - Expression of odorant-binding and chemosensory proteins and spatial map of
      chemosensilla on labial palps of Locusta migratoria (Orthoptera: Acrididae).
AB  - The sensilla on labial palps in Locusta migratoria were observed and mapped using
      light microscopy, scanning and transmission electron microscopy. A dome region on
      the tip of the fourth segment (distal segment) of labial palps is mainly covered
      with sensilla chaetica (about 98%), and few sensilla basiconica (2%). The total
      number of both types of sensilla is significantly higher in females than in
      males. Sensilla chaetica can be further subdivided into three groups containing
      6, 7 or 10 neurons. Immunocytochemical localization of odorant-binding protein
      (OBP) and chemosensory proteins (CSPs) was performed on ultrathin sections of
      sensilla on labial palps. The antiserum against odorant-binding protein from
      Locusta migratoria (LmigOBP) only labelled sensilla basiconica, with gold
      granules only found in the sensillum lymph. Chemosensory protein instead was
      specifically present in the outer sensillum lymph of all three subgroups of
      sensilla chaetica with antiserum against CSP-I from Schistocerca gregaria
      (SgreCSP-I). In contrast these three subgroups were never labelled with antiserum
      against CSP-II from Locusta migratoria (LmigCSP-II). In addition, a few sensilla
      chaetica could not be stained with any of the antisera used.

PMID- 18089058
TI  - Communities of microbes that inhabit the changing hindgut landscape of a
      subsocial beetle.
AB  - Microbes that have adopted endosymbiotic life styles not only have evolved to
      live in specialized habitats within living organisms, but the living habitats
      also have evolved to accommodate them. The hindgut of the passalid beetle
      (Odontotaenius disjunctus) is lined with a cuticle that undergoes dramatic
      topographic changes during the life cycle of the beetle. This manuscript
      addresses the changes that have been observed in time and space for the cuticular
      landscape of the hindgut as well as for the microbial communities within the
      hindgut. Microbial identity is based on morphology, culture, and extrapolation
      from previously reported passalid gut inhabitants.

PMID- 18089059
TI  - Ultrastructural changes in the midgut epithelium in Podura aquatica L. (Insecta,
      Collembola, Arthropleona) during regeneration.
AB  - Data considering the degeneration and regeneration of the midgut epithelium in
      the primitive wingless insects, such as Collembola, are rather poor. Also
      information, which treats the regenerative cells as the primordial cells, is
      poorly known. The midgut epithelium of Podura aquatica L. (Insecta, Collembola,
      Arthropleona) is formed by the epithelial and regenerative cells. The epithelial
      cells show distinct regionalisation in the organelles distribution. The
      ultrastructure of the basal, perinuclear and apical regions of the epithelial
      cells is described. As in insects without Malpighian tubules, structures which
      resemble urospherites occur in the cytoplasm of the epithelial cells. After
      degeneration of the entire midgut epithelium, a new epithelium is formed from
      regenerative cells. During the process of regeneration, the degenerated
      epithelium gradually is separated from the basal lamina by the newly formed one.
      Finally, the detached epithelium is moved into the midgut lumen. Regenerative
      cells play a role of primordial cells during epithelial regeneration.

PMID- 18089060
TI  - Morphology and ultrastructure of the Dufour gland in workers of social wasps
      (Hymenoptera, Vespidae).
AB  - The Dufour gland in workers of vespine wasps appears as an unpaired tubiform
      gland that opens in close proximity to the sting base. The epithelial cells that
      line the central reservoir are characterized by apical microvillus-like
      projections and deep basal invaginations. Their cytoplasm contains a well
      developed Golgi apparatus, numerous mitochondria, as well as strands of smooth
      endoplasmic reticulum. The Dufour gland duct occurs ventrally to the venom gland
      duct, and bends downward near the sting base to open in the dorsal vaginal wall.
      In this region, the duct is dorsoventrally flattened, and shows conspicuous
      bundles of parallel microtubules in the epithelial cells, that transmit the
      pulling forces of the myofilaments of the underlying muscular supply to the
      cuticle. This results in an active opening mechanism regulated by muscular
      contraction, while passive closure probably results from the return of the
      cuticular intima to a rest position.

PMID- 18089061
TI  - Sparse sensillar array on Trioza apicalis (Homoptera, Triozidae) antennae-an
      adaptation to high stimulus levels?
AB  - To investigate the morphological basis for olfactory reception in the carrot
      psyllid (Trioza apicalis) we used scanning and transmission electron microscopy.
      Our study reveals a very sparse sensillar setup. We identify and describe several
      different types of single-walled sensilla likely to have an olfactory function,
      as well as mechanosensory hairs and intracuticular sensilla. A T. apicalis
      antenna is about 0.6 mm long and has 10 segments. Apically on the flagellum there
      are two conspicuous multi-porous single-walled bristles. There are six cuticular
      cavities on the flagellum; two smaller on the apical flagellomere, and four
      larger located on the lateral side of the antenna on flagellomeres 2, 4, 6 and 7.
      Each cavity contains two sensilla and there are three varieties of cavity
      sensilla. Mechano- and chemosensory hairs appear in low numbers on all segments
      but the third. Carrot psyllids most likely use olfactory cues to locate their
      rather strongly smelling host plants, and we argue that the low number of
      olfactory sensilla found in this insect may accommodate high concentrations of
      odour stimuli. There is no sexual dimorphism in the sensillar setup. In
      concordance with this, no sex pheromones have been described in the Psylloidea so
      far.

PMID- 18089062
TI  - Distinctive presence of peritracheal athrocytes in Bombyx mori L. and Bombyx
      mandarina M. as compared to their absence in several other lepidopteran species.
AB  - Pericardial cells are present in a wide variety of insects and are thought to
      constitute the majority of 'athrocytes (nephrocytes)'. In contrast, peritracheal
      athrocytes have only been observed in Bombyx mori L. Although peritracheal
      athrocytes have a distinct morphology, it is unknown whether these cells are
      common to all lepidopterans. We anatomically compared eight lepidopteran species:
      Bombyx mori L. and Bombyx mandarina M. (Bombycidae); Samia cynthia ricini D.
      (Saturniidae); Agrius convolvuli L. (Sphingidae); Spodoptera litura F. and
      Mythimna separata W. (Noctuidae); Pieris rapae L. (Pieridae); and Glyphodes
      pyloalis W. (Crambidae). Of these species, only Bombyx mori L. and Bombyx
      mandarina M. possess peritracheal athrocytes.

PMID- 18089063
TI  - The larval development of the telotrophic meroistic ovary in the bug Dysdercus
      intermedius (Heteroptera, Pyrrhocoridae).
AB  - Bug ovaries are of the telotrophic meroistic type. Nurse cells are restricted to
      the anterior tropharium and are in syncytial connection with the oocytes via the
      acellular trophic core region into which cytoplasmic projections of oocytes and
      nurse cells open. The origin of intercellular connections in bug ovaries is not
      well understood. In order to elucidate the cellular processes underlying the
      emergence of the syncytium, we analysed the development of the ovary of Dysdercus
      intermedius throughout the five larval instars. Up to the third instar, the germ
      cell population of an ovariole anlage forms a single, tight rosette. In the
      center of the rosette, phosphotyrosine containing proteins and f-actin
      accumulate. This center is filled with fusomal cytoplasm and closely
      interdigitating cell membranes known as the membrane labyrinth. With the molt to
      the fourth instar germ cells enhance their mitotic activity considerably. As a
      rule, germ cells divide asynchronously. Simultaneously, the membrane labyrinth
      expands and establishes a central column within the growing tropharium. In the
      fifth instar the membrane labyrinth retracts to an apical position, where it is
      maintained even in ovarioles of adult females. The former membrane labyrinth in
      middle and posterior regions of the tropharium is replaced by the central core to
      which nurse cells and oocytes are syncytially connected. Germ cells in the most
      anterior part of the tropharium, i.e. those in close proximity to the membrane
      labyrinth remain proliferative. The posterior-most germ cells enter meiosis and
      become oocytes. The majority of the ovarioles' germ cells, located in between
      these two populations, endopolyploidize and function as nurse cells. We conclude
      that the extensive multiplication of germ cells and their syncytial assembly
      during larval development is achieved by incomplete cytokineses followed by
      massive membrane production. Membranes are degraded as soon as the trophic core
      develops. For comparative reasons, we also undertook a cursory examination of
      early germ cell development in Dysdercus intermedius males. All results were
      compatible with the known basic patterns of early insect spermatogenesis. Germ
      cells run through mitotic and meiotic divisions in synchronous clusters emerging
      from incomplete cytokineses. During the division phase, the germ cells of an
      individual cluster are connected by a polyfusome rich in f-actin.

PMID- 18089064
TI  - Structure of female genitalia of glassy-winged sharpshooter, Homalodisca
      coagulata (Say) (Hemiptera: Cicadellidae).
AB  - The functional reproductive morphology of the female glassy-winged sharpshooter,
      Homalodisca coagulata (Say), is described at both light microscopy and scanning
      electron microscopy levels. The female has nine abdominal segments; the seventh
      to the ninth abdominal segments are modified for reproduction; the eighth tergite
      is reduced to two segments, with the ovipositor partially exposed from the
      modified ninth segment-the pygofer. The pygofer, covered with trichoid and
      coeloconic sensilla, almost completely encloses the ovipositor, which consists of
      three pairs of valvulae and two pairs of valvifers. The first and second valvulae
      function together for oviposition. The first valvulae are located exterior to the
      second valvulae, both of which bear many trichoid, campaniform, and coeloconic
      sensilla. The third valvulae, possessing many coeloconic sensilla, envelope the
      first and second valvulae. Seven major muscles are found to be associated with
      the ovipositor and the pygofer. The oviposition process is described with respect
      to the activity of the valvulae and their associated musculature. The female
      morphology follows the general pattern of cicadellids as a group.

PMID- 18089065
TI  - Venom gland and reservoir morphology in cynipoid wasps.
AB  - The venom apparatus morphology was examined in 25 species of Cynipoidea,
      representing 11 parasitoid taxa; 12 gall inducers and two inquilines. Typically
      the venom apparatus consists of an oval or bilobed reservoir connected to the
      ovipositor apparatus by a very short venom duct at the anterior end and to a
      single elongate unbranched venom gland at or near its posterior end. The Dufour's
      gland was not found in any of the examined species. The elongate unbranched venom
      gland and the absence of the Dufour's gland are putative cynipoid synapomorphies.
      The shape and size of especially the venom reservoir were found to vary
      considerably within the Cynipoidea. It is typically less prominent in the
      parasitoid taxa than in the gall inducers. Exceptions include the poppy gallers
      Barbotinia and Aylax, in which the venom reservoirs were remarkably small and in
      the rose galler Diplolepis, where only a rudimentary venom apparatus was found.
      Possible functional and phylogenetic implications of cynipoid venom apparatus
      features are discussed.

PMID- 18089066
TI  - Cuticle differentiation during Drosophila embryogenesis.
AB  - The constitutive criterion for the evolutionary successful clade of ecdysozoans
      is a protective exoskeleton. In insects the exoskeleton, the so-called cuticle
      consists of three functional layers, the waterproof envelope, the proteinaceous
      epicuticle and the chitinous procuticle that are produced as an extracellular
      matrix by the underlying epidermal cells. Here, we present our electron
      microscopic study of cuticle differentiation during embryogenesis in the fruit
      fly Drosophila melanogaster. We conclude that cuticle differentiation in the
      Drosophila embryo occurs in three phases. In the first phase, the layers are
      established. Interestingly, we find that establishment of the layers occurs
      partially simultaneously rather than in a strict sequential manner as previously
      proposed. In the second phase the cuticle thickens. Finally, in the third phase,
      when secretion of cuticle material has ceased, the chitin laminae acquire their
      typical orientation, and the epicuticle of the denticles and the head skeleton
      darken. Our work will help to understand the phenotypes of embryos mutant for
      genes encoding essential cuticle factors, in turn revealing mechanisms of cuticle
      differentiation.

PMID- 18089067
TI  - Functional division of intrinsic neurons in the mushroom bodies of male
      Spodoptera littoralis revealed by antibodies against aspartate, taurine, FMRF
      amide, Mas-allatotropin and DC0.
AB  - The aim of this study was to further reveal the organization of Kenyon cells in
      the mushroom body calyx and lobes of the male moth Spodoptera littoralis, by
      using immunocytochemical labeling. Subdivisions of the mushroom bodies were
      identified employing antisera raised against the amino acids taurine and
      aspartate, the neuropeptides FMRF-amide and Mas-allatotropin, and against the
      protein kinase A catalytic subunit DC0. These antisera have previously been shown
      to label subsets of Kenyon cells in other species. The present results show that
      the organization of the mushroom body lobes into discrete divisions, described
      from standard neuroanatomical methods, is confirmed by immunocytology and shown
      to be further elaborated. Anti-taurine labels the accessory Y-tract, the gamma
      division of the lobes, and a thin subdivision of the most posterior component of
      the lobes. Aspartate antiserum labels the entire mushroom body. FMRF-amide-like
      immunolabeling is pronounced in the gamma division and in the anterior perimeter
      of the alpha/beta and alpha'/beta' divisions. Mas-allatotropin-like
      immunolabeling shows the opposite of FMRF-amide-like and taurine-like
      immunolabeling: the gamma division and the accessory Y-system is immunonegative
      whereas strong labeling is seen in both the alpha/beta and alpha'/beta'
      divisions. The present results agree with findings from other insects that
      mushroom bodies are anatomically divided into discrete parallel units. Functional
      and developmental implications of this organization are discussed.

PMID- 18089068
TI  - The organization and evolutionary implications of neuropils and their neurons in
      the brain of the onychophoran Euperipatoides rowelli.
AB  - This account describes the organization of the brain of the adult Euperipatoides
      rowelli, a member of the Onychophora or "velvet worms." The present account
      identifies three cerebral divisions, the first of which contains primary
      olfactory neuropils, visual neuropils, and brain regions that correspond
      anatomically to the mushroom bodies of annelids, chelicerates, myriapods, and
      insects. In common with the brains of many chelicerates, the onychophoran brain
      is supplied by many thousands of uniformly small basophilic perikarya. Other
      chelicerate-like features include mushroom body lobes that extend across the
      brain's midline, an unpaired arch-shaped midline neuropil, and visual pathways
      that supply midline neuropil and that of the mushroom bodies. These and other
      similarities with chelicerate brains are discussed in the context of arthropod
      evolution and with reference to recent molecular phylogenies.

PMID- 18089069
TI  - Different oviposition behaviour in Chrysomelid beetles: Characterisation of the
      interface between oviposition secretion and the plant surface.
AB  - The behavioural sequence of the oviposition process can be quite distinct in
      herbivorous leaf beetles: eggs are either connected to the plant surface or laid
      into mesophyll tissue. Females of two beetle species were recorded with a digital
      camera in order to analyse their oviposition behaviour. The morphology of the
      plant-egg-interface was investigated in three species by histological studies and
      scanning electron microscopy. The lily leaf beetle, Lilioceris lilii, oviposits
      directly on the plant cuticle without damaging the plant tissue. Several eggs are
      released together with secretion and are laid in a row. The secretion sorbes in
      the plant cuticle. In the close relative, Lilioceris merdigera, the secretion can
      enter the leaf tissue via the stomata. The mustard leaf beetle, Phaedon
      cochleariae, gnaws a characteristic hole into the epidermis and part of the
      mesophyll. Into this cavity, it releases in an alternating sequence secretion, a
      single egg and again secretion. The egg, which is usually laid on plants growing
      in wetlands, is surrounded by an extrachorion that might possess a respiratory
      function. The potential eco-physiological relevance of the specific nature of the
      placement of eggs and secretion on or in the plant tissue is discussed.

PMID- 18089071
TI  - Origin and evolution of arthropod visual systems. Introduction.

PMID- 18089072
TI  - Photoreceptor cells and eyes in Annelida.
AB  - The evolution of photoreceptor cells and eyes in Metazoa is far from being
      resolved, although recent developmental and morphological studies provided strong
      evidence for a common origin of photoreceptor cells and existence of sister cell
      types in early metazoans. Photoreceptor cells are of two types, rhabdomeric and
      ciliary, depending on which part of the cells is involved in photoreception
      proper. A crucial point in understanding eye evolution is the explanation of the
      enormous structural diversity of photoreceptor cells and visual systems, given
      the general tendency for molecular conservation. One example of such diversity
      occurs in Annelida. In this taxon three types of photoreceptor cells exist:
      rhabdomeric, ciliary and phaosomous sensory cells. Whether the latter evolved
      independently or have been derived from one of the former cell types is still
      unresolved, since cilia and microvilli are found in these cells. These different
      photoreceptor cells are present in cerebral ocelli and eyes, in various ectopic
      ocelli and eyes situated in different places as well as in various photoreceptor
      like sense organs. Whereas rhabdomeric cells mostly occur in connection with
      pigmented supportive cells, the other types are usually found with unpigmented
      supportive cells. Thus for the latter cells clear evidence for photoreception is
      still lacking in most cases. However, initial molecular-developmental
      investigations have shown that in fact ciliary photoreceptor cells exist within
      Annelida. Certain visual systems are only present during the larval phase and
      either replaced by the adult eyes or completely reduced during postlarval and
      adult stages. In the present paper the diversity of cerebral and extracerebral
      photoreceptor cells and ocelli as well as corresponding organs devoid of shading
      pigment is reviewed in Annelida.

PMID- 18089073
TI  - Structure and development of onychophoran eyes: what is the ancestral visual
      organ in arthropods?
AB  - Scarce and controversial information on visual organs and their innervation in
      Onychophora currently do not allow a thorough comparison with Euarthropoda.
      Therefore, this study sets out to provide additional data on the architecture and
      morphogenesis of the onychophoran visual system and to explore similarities and
      differences between the visual organs of onychophorans and other arthropods.
      Based on the new data for Epiperipatus biolleyi (Peripatidae) and Metaperipatus
      blainvillei (Peripatopsidae), it is suggested that the compound eyes represent an
      autapomorphy of Euarthropoda since similarities with the onychophoran eyes are
      weak or absent. Instead, the innervation from a central rather than lateral part
      of the brain, the presence of only one (paired or unpaired) visual center, and a
      similar ontogenetic origin from an ectodermal groove rather than a proliferation
      zone suggest homology between the onychophoran eyes and the median ocelli of
      euarthropods. In conclusion, I suggest that the last common ancestor of
      arthropods bore only one pair of ocellus-like visual organs that were modified in
      several arthropod lineages. This hypothesis is supported by recent
      paleontological data.

PMID- 18089074
TI  - The eyes of trilobites: The oldest preserved visual system.
AB  - The oldest preserved visual systems are to be found in the extinct trilobites,
      marine euarthropods which existed between about 520 and 250 million years ago.
      Because they possessed a calcified cuticle, they have a good fossil record, and
      commonly the lens-bearing surfaces of their paired compound eyes are well
      preserved. The sublensar structures, however, remain unknown. Three kinds of eyes
      have been distinguished. Holochroal eyes, apomorphic for trilobites, typically
      have many contiguous small lenses, set on a kidney-shaped visual surface. Lens
      optics, angular range of vision, and ontogeny have been established for many
      compound eyes. Some pelagic trilobites have enormous eyes, subtending a panoramic
      field of view. Schizochroal eyes are found only in one group, the phacopids
      (Ordovician to Devonian). These have large lenses, separated from each other by
      cuticular material, and the lenses have a complex doublet or triplet internal
      structure, which could focus light sharply. The optics of phacopid eyes are
      becoming increasingly well known despite the fact that there are no direct
      counterparts in any living arthropods today. Schizochroal eyes are apomorphic for
      phacopids and were derived by paedomorphosis from a holochroal precursor.
      Abathochroal eyes are confined to a short-lived Cambrian group, the eodiscids (of
      which most representatives were blind). Less is known about them than other
      trilobite eyes and their origins remain obscure. Some trilobite groups had no
      eyes, but had other kinds of sensory organs. In Upper Devonian times several
      groups of trilobites independently underwent progressive eye-reduction leading to
      blindness, related to prevailing environmental conditions of the time. The last
      trilobites (of Carboniferous and Permian age), however, had normal holochroal
      eyes, which persisted until the final extinction of trilobites at the end of the
      Permian.

PMID- 18089075
TI  - The eyes of Limulus polyphemus (Xiphosura, Chelicerata) and their afferent and
      efferent projections.
AB  - The visual system of the American horseshoe crab Limulus polyphemus (L.
      polyphemus) is an important preparation for studying the photoresponse, the
      circadian modulation of the photoresponse and visual information processing.
      Given its unique position in phylogeny the structure of its visual system also
      informs studies of the relationships among arthropods and the characteristics of
      eurarthropods. Much has been learned about the organization of the relatively
      simple L. polyphemus visual system, but much remains to be discovered. This
      review summarizes current knowledge of the structure of L. polyphemus eyes and
      the organization of their afferent and efferent projections and points to
      important unanswered questions.

PMID- 18089076
TI  - The frontal eyes of crustaceans.
AB  - Frontal eyes of crustaceans (previously called nauplius eye and frontal organs)
      are usually simple eyes that send their axons to a medial brain centre in the
      anterior margin of the protocerebrum. Investigations of a large number of recent
      species within all major groups of the Crustacea have disclosed four kinds of
      frontal eyes correlated with taxonomic groups and named after them as the
      malacostracan, ostracod-maxillopodan, anostracan, and phyllopodan frontal eyes.
      The different kinds of eyes have been established using the homology concept
      coined by Owen [Owen, R., 1843. Lectures on the comparative anatomy and
      physiology of the invertebrate animals. Longman, Brown, Green, Longmans, London]
      and the criteria for homology recommended by Remane [Remane, A., 1956. Die
      Grundlagen des naturlichen Systems, der vergleichenden Anatomie und der
      Phylogenetik. 2nd ed. Akademische Verlagsgesellschaft, Geest und Portig,
      Leipzig]. Common descent is not used as a homology criterion. Frontal eyes bear
      no resemblance to compound eyes and in the absence of compound eyes, as in the
      ostracod-maxillopodan group, frontal eyes develop into complicated mirror, lens
      mirror, and scanning eyes. Developmental studies demonstrate widely different
      ways to produce frontal eyes in phyllopods and malacostracans. As a result of the
      studies of recent frontal eyes in crustaceans, it is concluded by extrapolation
      that in crustacean ancestors four non-homologous frontal eye types evolved that
      have remained functional in spite of concurrent compound eyes.

PMID- 18089077
TI  - Ocellar optics in nocturnal and diurnal bees and wasps.
AB  - Nocturnal bees, wasps and ants have considerably larger ocelli than their diurnal
      relatives, suggesting an active role in vision at night. In a first step to
      understanding what this role might be, the morphology and physiological optics of
      ocelli were investigated in three tropical rainforest species - the nocturnal
      sweat bee Megalopta genalis, the nocturnal paper wasp Apoica pallens and the
      diurnal paper wasp Polistes occidentalis - using hanging-drop techniques and
      standard histological methods. Ocellar image quality, in addition to lens focal
      length and back focal distance, was determined in all three species. During
      flight, the ocellar receptive fields of both nocturnal species are centred very
      dorsally, possibly in order to maximise sensitivity to the narrow dorsal field of
      light that enters through gaps in the rainforest canopy. Since all ocelli
      investigated had a slightly oval shape, images were found to be astigmatic:
      images formed by the major axis of the ocellus were located further from the
      proximal surface of the lens than images formed by the minor axis. Despite being
      astigmatic, images formed at either focal plane were reasonably sharp in all
      ocelli investigated. When compared to the position of the retina below the lens,
      measurements of back focal distance reveal that the ocelli of Megalopta are
      highly underfocused and unable to resolve spatial detail. This together with
      their very large and tightly packed rhabdoms suggests a role in making sensitive
      measurements of ambient light intensity. In contrast, the ocelli of the two wasps
      form images near the proximal boundary of the retina, suggesting the potential
      for modest resolving power. In light of these results, possible roles for ocelli
      in nocturnal bees and wasps are discussed, including the hypothesis that they
      might be involved in nocturnal homing and navigation, using two main cues: the
      spatial pattern of bright patches of daylight visible through the rainforest
      canopy, and compass information obtained from polarised skylight (from the
      setting sun or the moon) that penetrates these patches.

PMID- 18089078
TI  - Evolution of color and vision of butterflies.
AB  - Butterfly eyes consist of three types of ommatidia, which are more or less
      randomly arranged in a spatially regular lattice. The corneal nipple array and
      the tapetum, optical structures that many but not all butterflies share with
      moths, suggest that moths are ancestral to butterflies, in agreement with
      molecular phylogeny. A basic set of ultraviolet-, blue- and green-sensitive
      receptors, encountered among nymphalid butterflies, forms the basis for
      trichromatic vision. Screening pigments surrounding the light-receiving rhabdoms
      can modify the spectral sensitivity of the photoreceptors so that the sensitivity
      peak is in the violet, yellow, red, or even deep-red, specifically in
      swallowtails (Papilionidae) and whites (Pieridae), thus enhancing color
      discriminability. The photoreceptor sensitivity spectra are presumably tuned to
      the wing colors of conspecific butterflies.

PMID- 18089079
TI  - Evolution of eye development in arthropods: phylogenetic aspects.
AB  - The architecture of the adult arthropod visual system for many decades has
      contributed important character sets that are useful for reconstructing the
      phylogenetic relationships within this group. In the current paper we explore
      whether aspects of eye development can also contribute new arguments to the
      discussion of arthropod phylogeny. We review the current knowledge on eye
      formation in Trilobita, Xiphosura, Myriapoda, Hexapoda, and Crustacea. All
      euarthropod taxa share the motif of a proliferation zone at the side of the
      developing eye field that contributes new eye elements. Two major variations of
      this common motif can be distinguished: 1. The "row by row type" of Trilobita,
      Xiphosura, and Diplopoda. In this type, the proliferation zone at the side of the
      eye field generates new single, large elements with a high and variable cell
      number, which are added to the side of the eye and extend rows of existing eye
      elements. Cell proliferation, differentiation and ommatidial assembly seem to be
      separated in time but spatially confined within the precursors of the optic units
      which grow continuously once they are formed (intercalary growth). 2. The
      "morphogenetic front type" of eye formation in Crustacea+Hexapoda (Tetraconata).
      In this type, there is a clear temporal and spatial separation of the formation
      and differentiation processes. Proliferation and the initial steps of pattern
      formation take place in linear and parallel mitotic and morphogenetic fronts (the
      mitotic waves and the morphogenetic furrow/transition zone) and numerous but
      small new elements with a strictly fixed set of cells are added to the eye field.
      In Tetraconata, once formed, the individual ommatidia do not grow any more.
      Scutigeromorph chilopods take an intermediate position between these two major
      types. We suggest that the "row by row type" as seen in Trilobita, Xiphosura and
      Diplopoda represents the plesiomorphic developmental mode of eye formation from
      the euarthropod ground pattern whereas the "morphogenetic front type" is
      apomorphic for the Tetraconata. Our data are discussed with regard to two
      competing hypotheses on arthropod phylogeny, the "Tracheata" versus "Tetraconata"
      concept. The modes of eye development in Myriapoda is more parsimonious to
      explain in the Tetraconata hypothesis so that our data raise the possibility that
      myriapod eyes may not be secondarily reconstructed insect eyes as the prevailing
      hypothesis suggests.

PMID- 18089080
TI  - Tracking down the "head blob": comparative analysis of wingless expression in the
      developing insect procephalon reveals progressive reduction of embryonic visual
      system patterning in higher insects.
AB  - The evolution of larval head morphology in holometabolous insects is
      characterized by reduction of antennal appendages and the visual system
      components. Little insight has been gained into molecular developmental changes
      underlying this morphological diversification. Here we compare the expression of
      the segment polarity gene wingless (wg) in the pregnathal head of fruit fly,
      flour beetle and grasshopper embryos. We provide evidence that wg activity
      contributes to segment border formation, and, subsequently, the separation of the
      visual system and protocerebrum anlagen in the anterior procephalon. In directly
      developing insects like grasshopper, seven expression domains are formed during
      this process. The activation of four of these, which correspond to polar
      expression pairs in the optic lobe anlagen and the protocerebral ectoderm, has
      shifted to postembryonic stages in flour beetle and Drosophila. The remaining
      three domains map to the protocerebral neuroectoderm, and form by disintegration
      of a large precursor domain in flour beetle and grasshopper. In Drosophila, the
      precursor domain remains intact, constituting the previously described "head
      blob". These data document major changes in the expression of an early patterning
      gene correlated with the dramatic evolution of embryonic visual system
      development in the Holometabola.

PMID- 18089081
TI  - Ancient mechanisms of visual sense organ development based on comparison of the
      gene networks controlling larval eye, ocellus, and compound eye specification in
      Drosophila.
AB  - Key mechanisms of development are strongly constrained, and hence often shared in
      the formation of highly diversified homologous organs. This diagnostic is applied
      to uncovering ancient gene activities in the control of visual sense organ
      development by comparing the gene networks, which regulate larval eye, ocellus
      and compound eye specification in Drosophila. The comparison reveals a suite of
      shared aspects that are likely to predate the diversification of arthropod visual
      sense organs and, consistent with this, have notable similarities in the
      developing vertebrate visual system: (I) Pax-6 genes participate in the
      patterning of primordia of complex visual organs. (II) Primordium determination
      and differentiation depends on formation of a transcription factor complex that
      contains the products of the selector genes Eyes absent and Sine oculis. (III)
      The TGF-beta signaling factor Decapentaplegic exerts transcriptional activation
      of eyes absent and sine oculis. (IV) Canonical Wnt signaling contributes to
      primordium patterning by repression of eyes absent and sine oculis. (V)
      Initiation of determination and differentiation is controlled by hedgehog
      signaling. (VI) Egfr signaling drives retinal cell fate specification. (VII) The
      proneural transcription factor atonal regulates photoreceptor specification.
      (VII) The zinc finger gene glass regulates photoreceptor specification and
      differentiation.

PMID- 18089082
TI  - Pax6 and eye development in Arthropoda.
AB  - The arthropod compound eye is one of the three main types of eyes observed in the
      animal kingdom. Comparison of the eyes seen in Insecta, Crustacea, Myriapoda and
      Chelicerata reveals considerable variation in terms of overall cell number, cell
      positioning, and photoreceptor rhabdomeres, yet, molecular data suggest there may
      be unexpected similarities. We review here the role of Pax6 in eye development
      and evolution and the relationship of Pax6 with other retinal determination genes
      and signaling pathways. We then discuss how the study of changes in Pax6 primary
      structure, in the gene networks controlled by Pax6 and in the relationship of
      Pax6 with signaling pathways may contribute to our insight into the relative role
      of conserved molecular-genetic mechanisms and emergence of evolutionary novelty
      in shaping the ommatidial eyes seen in the Arthropoda.

PMID- 18089083
TI  - Morphology and ultrastructure of a bacteria cultivation organ: the antennal
      glands of female European beewolves, Philanthus triangulum (Hymenoptera,
      Crabronidae).
AB  - Females of a solitary digger wasp, the European beewolf (Philanthus triangulum
      F.), cultivate symbiotic bacteria of the genus Streptomyces in specialized
      antennal glands. The streptomycetes are secreted in the subterranean brood cells
      and protect the offspring against mould fungi. We reconstructed the complex
      morphology of the antennal glands using 3D-visualization software, investigated
      the ultrastructure of the glands, and examine the role of the antennal glands as
      organs for the cultivation of the symbiotic bacteria. The bacteria are cultivated
      in five antennomeres within large reservoirs that consist of two slightly bent
      lobes. Each gland reservoir is bordered by a monolayered epithelium lined with a
      partially reinforced cuticle and when completely filled with bacteria it
      comprises about half of the antennomere's volume. The opening of the reservoir is
      covered by gelatinous appendage of the cuticle. The cells of the monolayered
      epithelium bordering each reservoir show basal invaginations, apical microvilli
      and numerous vesicles. Each reservoir is surrounded by approximately 400 class 3
      gland units that are connected to the reservoir lumen through conducting canals.
      The class 3 gland cells contain numerous vesicles and a high density of rough
      endoplasmatic reticulum. In the reservoir lumen, large numbers of symbiotic
      Streptomyces bacteria are embedded in secretion droplets. Thus, the bacteria are
      apparently provided with large amounts of nutrients via the gland epithelium and
      the class 3 gland cell units.

PMID- 18089084
TI  - The eyes of Macrosoma sp. (Lepidoptera: Hedyloidea): a nocturnal butterfly with
      superposition optics.
AB  - The visual system of nocturnal Hedyloidea butterflies was investigated for the
      first time, using light and electron microscopy. This study was undertaken to
      determine whether hedylids possess the classic superposition eye design
      characteristic of most moths, or apposition eyes of true butterflies
      (Papilionoidea), and, to gain insights into the sensory ecology of the
      Hedyloidea. We show that Macrosoma heliconiaria possesses a superposition-type
      visual mechanism, characterized by long cylindrical crystalline cones, a lack of
      corneal processes, 8 constricted retinular sense cells, rhabdoms separated from
      the crystalline cones forming a translucent 'clear zone', and tight networks of
      trachea that form a tapetum proximal to the retina and which also surround the
      rhabdoms to form a tracheal sheath. Dark-adapted individuals of M. heliconiaria,
      M. conifera, and M. rubidinarea exhibited distal retinular pigment migration,
      forming an eye glow. Correspondingly, light-exposure induced pigment to migrate
      proximally, causing the eye glow to be replaced by a dark pseudopupil. Other
      characteristics of the visual system, including relative eye size, facet size,
      and external morphology of the optic lobes, are mostly 'moth like' and correlate
      with an active, nocturnal lifestyle. The results are discussed in relation to the
      evolution of lepidopteran eyes, and the sensory ecology of this poorly understood
      butterfly superfamily.

PMID- 18089085
TI  - The antennal lobe of the African malaria mosquito, Anopheles gambiae -
      innervation and three-dimensional reconstruction.
AB  - Antibody labelling and subsequent three-dimensional reconstructions of the
      primary olfactory centres, the antennal lobes, of male and female African malaria
      mosquitoes, Anopheles gambiae, revealed 61 and 60 glomerular neuropils
      respectively. In addition to the small difference in number of glomeruli, sexual
      dimorphism was observed in both the size of the antennal lobe and of individual
      glomeruli. Furthermore, sexual specificity was observed within the array.
      Anterograde staining of afferents from peripheral olfactory organs support the
      reconstruction of the glomerular array. Although anterograde stainings support an
      organotopic organization of the antennal lobe, convergence of afferents
      originating from different organs into single glomeruli is observed. This
      finding, in both A. gambiae and A. aegypti, may shed new light upon the
      development and function of the olfactory system.

PMID- 18089086
TI  - Ultrastructural aspects of spermiogenesis and synspermia in the brown spider
      Loxosceles intermedia (Araneae: Sicariidae).
AB  - This study reports ultrastructural and cytochemical aspects of spermiogenesis and
      synspermia in the brown spider Loxosceles intermedia. The roundish early
      spermatids are initially interconnected by cytoplasmic bridges, forming groups of
      four cells. During spermiogenesis, these cells pass through a series of
      modifications: (1) progressive nuclear condensation brings chromatin into a
      fibrillar arrangement; (2) the nucleus becomes long and asymmetric, with a short
      post-centriolar elongation; (3) formation of the long, cone-shaped acrosome and
      the F-actin acrosomal filament; (4) establishment of the implantation fossa and
      the 9x2+3 pattern flagellum, which extends away from the sperm cell body.
      Eventually, the entire cell undergoes twisting and folding resulting in a
      synspermium, containing four sperm cells in which the flagellum and nucleus are
      delimitated by the plasma membrane, as individualized structures, but remain
      involved by the fused remaining cytoplasm and plasma membrane. Reaching the vas
      deferens, the synspermia are surrounded by a basic glycoproteic secretion.
      Synspermia are considered a derivative character, probably developed in this
      Sicariidae species, as well as in other Haplogynae, as an adaptation to improve
      the reproductive strategy.

PMID- 18089087
TI  - Sperm morphology of the neotropical harvestman Iporangaia pustulosa (Arachnida:
      Opiliones): comparative morphology and functional aspects.
AB  - We describe herein the sperm morphology of the harvestman Iporangaia pustulosa.
      Adult males were dissected, the reproductive tract was schematized and the
      seminal vesicle was processed by light, transmission and scanning electron
      microscopy. The male reproductive tract is composed of a tubular testis, two
      deferent ducts, a seminal vesicle, a propulsive organ and a penis, similar to
      that observed in other Opiliones. The spermatozoa from the seminal vesicle are
      oval, aflagellate and immotile, presenting a nucleus surrounding an invagination
      of the cytoplasm, as well as a complex acrosome and projections on the cell
      surface. In the testis, spermatozoa are devoid of projections. In the seminal
      vesicle, they gradually acquire the projections with tufts adhering to it.
      Consequently, spermatozoa in various distinct stages of projection development
      can be found in the seminal vesicle. We believe that these projections (1) could
      help transport sperm along the male and perhaps female reproductive tracts; (2)
      are used to anchor the spermatozoa inside the female spermatheca in order to
      avoid mechanical displacement by the genitalia of other males and (3) may play a
      role in oocyte recognition. We propose that the evolution of aflagellarity in
      Opiliones is related to the unique morphology of the female reproductive tract.
      Since eggs are fertilized on the tip of the ovipositor just prior to being laid,
      there is no advantage favoring sperm mobility. Additionally, female sperm
      receptacles are small and males that produced small spermatozoa would have a
      higher chance of fertilizing more eggs.

PMID- 18089088
TI  - Structure and development of setae on the thoracic limbs of the anostracan
      crustacean, Thamnocephalus platyurus.
AB  - Setae are a prominent feature of arthropod limbs. In taxa where the limbs develop
      during the larval phase, developing setae are an integral part of the developing
      limb bud and their differentiation cannot easily be separated from the early
      patterning and formation of the overall limb. Here I describe the morphogenesis
      and adult setae in a branchiopod crustacean, the anostracan, Thamnocephalus
      platyurus. The majority of the setae on the limbs are non-innervated plumose
      setae that are formed from six underlying cells. Because branchiopods are often
      sampled in comparative studies of limb development, the details of the cellular
      morphogenesis of their limbs provide a necessary basis for studies of limb
      patterning.

PMID- 18089089
TI  - Morphology of the prosomal endoskeleton of Scorpiones (Arachnida) and a new
      hypothesis for the evolution of cuticular cephalic endoskeletons in arthropods.
AB  - Skeletomuscular anatomy of the scorpion prosoma is examined in an attempt to
      explain the evolution of two endoskeletal features, a muscular diaphragm dividing
      the prosoma and opisthosoma and cuticular epistomal entapophyses with a uniquely
      complex arrangement of muscles, tendons and ligaments. Both structures appear to
      be derived from modifications of the mesodermal intersegmental endoskeleton that
      is primitive for all major arthropod groups. The scorpion diaphragm is a compound
      structure comprising axial muscles and pericardial ligaments of segments VI to
      VIII and extrinsic muscles of leg 4 brought into contact by longitudinal
      reduction of segment VII and integrated into a continuous subvertical sheet. This
      finding reconciles a long-standing conflict between one interpretation of
      opisthosomal segmentation based on scorpion embryology and another derived from
      comparative skeletomuscular anatomy. A new evolutionary-developmental mechanism
      is proposed to account for the complex morphology of the epistomal entapophyses.
      Each entapophysis receives 14 muscles and tendons that in other taxa would attach
      to the anterior connective endoskeleton in the same relative positions. This
      observation suggests that the embryological precursor to the connective
      endoskeleton can initiate and guide ectodermal invagination and thereby serve as
      a spatial template for the development of cuticular apodemes. This mesoderm
      template model of ectodermal invagination is potentially applicable to all
      arthropods and may explain structural diversity and convergence in cephalic
      apodemes throughout the group. The model is used to interpret the cephalic
      endoskeletons of two non-chelicerate arthropods, Archaeognatha (Hexapoda) and
      Symphyla (Myriapoda), to demonstrate the generality of the model.

PMID- 18089091
TI  - Comparative study of the femoral organ in Zodarion spiders (Araneae: Zodariidae).
AB  - The femoral organ of Zodarion spiders has not been investigated in detail yet. In
      this study we describe the external and internal structure of this organ. The
      organ is situated at the distal tip of the femora of all the legs during all
      developmental stages. The size of the organ (expressed as the number of hairs)
      increased with the ontogenetic development of Zodarion species. The organ was
      confirmed to occur in both sexes of all 47 Zodarion species examined. It is
      possibly present in all species of this genus. The size of the organ increased
      with the size of the species. A comparative anatomical study was performed in
      juveniles and adults of both sexes of Zodarion rubidum, and females of both Z.
      cyrenaicum and Z. jozefienae. The femoral organ represents an exocrine gland
      composed of a group of secretory cells located below the epidermis. Each gland
      cell is connected with the leg surface by a single duct. The ducts run in
      intercellular spaces and specialised canal cells are lacking. The structure of
      the secretory cells, namely the abundance of smooth endoplasmic reticulum,
      suggests that the gland produces a volatile compound(s). The composition and the
      role of the secretion, however, remains unknown.

PMID- 18089092
TI  - A 'social' gland in a solitary wasp? The postpharyngeal gland of female European
      beewolves (Hymenoptera, Crabronidae).
AB  - Exocrine glands play an important role in maintaining the integrity of colonies
      of social Hymenoptera. The postpharyngeal gland (PPG) of ants is crucial for the
      generation of a nest odour that enables nestmate recognition. The evolutionary
      history of this gland is unknown and it was thought to be restricted to ants.
      Here we describe an exocrine head gland in females of a solitary crabronid wasp,
      the European beewolf, Philanthus triangulum, that resembles the PPG of ants in
      many respects. The newly described gland has the same location and the same glove
      like shape as in ants, and it also has a monolayered epithelium with similar
      ultrastructure. Unlike in ants, the epithelium bears hairs that reach into the
      lumen of the gland. Although the PPG of beewolves serves a completely different
      function it is also associated to an allogrooming behaviour as in ants. Based on
      these morphological and behavioural similarities as well as similarities in the
      chemical composition of the content of the PPG of both taxa, we hypothesise that
      the PPGs of ants and beewolves have a common evolutionary origin. Thus, our
      results suggest that the PPG in ants might not have evolved in response to social
      requirements but might have already existed in solitary predecessors.

PMID- 18089093
TI  - Males of a solitary wasp possess a postpharyngeal gland.
AB  - The postpharyngeal gland has long been thought to occur only in ants. Here we
      characterize, by use of light and electron microscopy as well as 3D
      reconstruction based on nuclear magnetic resonance (NMR) imaging data, a large
      cephalic gland reservoir of males of a solitary digger wasp, the European
      beewolf, Philanthus triangulum. Several lines of evidence suggest that this
      reservoir is a postpharyngeal gland. The gland reservoir originates from the
      posterior part of the pharynx and consists of two pairs of unbranched tubular
      structures that occupy a large portion of the head capsule. Its wall is composed
      of a unicellular epithelium that is lined by a cuticle. The gland contains a
      blend of hydrocarbons and compounds with functional groups, and we show that the
      hydrocarbon fraction of the pheromone is congruent with the hydrocarbons on the
      cuticle. We discuss the implications of our findings for the evolution of the
      postpharyngeal gland in ants.

PMID- 18089094
TI  - Comparative morphology of cephalic exocrine glands among castes of the black ant
      Lasius niger.
AB  - The glandular system is crucially involved in main aspects of ant social life.
      The function of glands has been primarily studied in the workers (the non
      reproductive individuals in a colony). In contrast, little information is
      available on queens (the reproductive females in a colony) or males in spite of
      the obvious functional differences between these castes. Here we report a
      comparison of the general morphology of the mandibular, propharyngeal and
      postpharyngeal glands between the three castes of the black ant Lasius niger. The
      analysis clearly shows that all these cephalic glands differ in relative size
      between castes and suggests a link between gland structure and its behavioral
      role in queens, workers and males. In particular, males present a hypertrophied
      mandibular gland. This is consistent with the fact that these glands might be the
      source of the sex pheromone in this caste. By contrast, queens exhibited the most
      developed postpharyngeal glands. This is consistent with the production of
      particular cues by queens for workers to help them to distinguish between
      reproductive and non-reproductive females. Finally, the propharyngeal glands were
      most developed in the worker caste and of similar relative size in males and
      queens. Their function is still enigmatic.

PMID- 18089095
TI  - The nervous system of Leptodora kindtii (Branchiopoda, Cladocera) surveyed with
      confocal scanning microscopy (CLSM), including general remarks on the branchiopod
      neuromorphological ground pattern.
AB  - The present study describes the nervous system of Leptodora kindtii Focke, 1844
      (Branchiopoda, Cladocera) and compares it with that of other branchiopods, with
      the aim of determining the characters of the branchiopod neuromorphological
      ground pattern. L. kindtii shares certain correspondences with all studied
      branchiopods, including a diffuse deutocerebrum, a separated tritocerebrum and a
      ventral nerve cord with two commissures in each segment. We document a central
      complex consisting of central body, a protocerebral bridge and lateral lobes
      which is homologous to that recently described for the anostracan Artemia salina
      Linnaeus, 1758 and also known for malacostracans. Other characters in L. kindtii,
      such as the fused compound eye, are shared with other cladocerans, and some, such
      as optic fibres, the elongated circumoesophageal connectives and the short
      ventral nerve cord without ganglia in the thoracal part, are unique to Leptodora.
      The innervation of the "lateral lobes" of the "lower lip" indicates a
      correspondence between these lobes and the maxillules. We found evidence that the
      ganglia of the maxillula and maxilla segments have not been incorporated in other
      ganglia, as suggested earlier.

PMID- 18089096
TI  - Dorsal longitudinal stretch receptor of Drosophila melanogaster larva - fine
      structure and maturation.
AB  - Insects possess two types of sensory neurons: ciliated type I sensory neurons
      that innervate external sensory organs and chordotonal organs, and type II
      sensory neurons that form a subepidermal plexus or innervate stretch receptors.
      Among stretch receptors, a dorsel longitudinal stretch receptor is highly
      conserved in insects, being found in all insect orders investigated. Here we
      describe the topology and anatomical structure of this receptor in the fruit fly
      embryo and larva using transmission electron microscopy and single cell staining
      for fluorescence microscopy. The receptor is composed of the dorsal bipolar
      dendrite neuron, which arises from an archetypal cell lineage, its sister glial
      cell and the peripheral glial cell accompanying the nerve. The neuron is situated
      among the muscles in the dorsal body wall on the intersegmental nerve. Its two
      dendrites stretch the length of the segment to the segmental folds. The neuron is
      wrapped by both glial cells and surrounded by a common basal lamina, which fans
      out at the dendritic tips to attach them to the epidermal cells at the segmental
      borders.

PMID- 18089097
TI  - An excretory organ in the Mystacocarida (Crustacea).
AB  - An excretory antennal gland, composed of only eight cells, is found entirely in
      the limb in the mystacocarid Derocheilocaris typica. The end sac is composed of
      podocytes, valve cells and cap cells. The podocytes contain enormous residual
      vesicles. There are few pedicel complexes, and they arise directly from the cell
      surface without intermediate foot processes. The excretory duct is entirely lined
      with microvilli, which are separated from the lumen by a modified layer of thin
      cuticle.

PMID- 18089098
TI  - The midgut ultrastructure of the endoparasite Xenos vesparum (Rossi) (Insecta,
      Strepsiptera) during post-embryonic development and stable carbon isotopic
      analyses of the nutrient uptake.
AB  - Females of the endoparasite Xenos vesparum (Strepsiptera, Stylopidae) may survive
      for months inside the host Polistes dominulus (Hymenoptera, Vespidae). The midgut
      structure and function in larval instars and neotenic females has been studied by
      light and electron microscope and by stable carbon isotopic technique. The 1st
      instar larva utilizes the yolk material contained in the gut lumen, whereas the
      subsequent larval instars are actively involved in nutrient uptake from the wasp
      hemolymph and storage in the adipocytes. At the end of the 4th instar, the
      neotenic female extrudes with its anterior region from the host; the midgut
      progressively degenerates following an autophagic cell death program. First the
      midgut epithelial cells accumulate lamellar bodies and then expel their nuclei
      into the gut lumen; the remnant gut consists of a thin epithelium devoid of
      nuclei but still provided with intercellular junctions. We fed the parasitized
      wasps with sugar from different sources (beet or cane), characterized by their
      distinctive carbon isotope compositions, and measured the bulk (13)C/(12)C ratios
      of both wasps and parasites. Female parasites developing inside the wasp hemocoel
      are able to absorb nutrients from the host but, after their extrusion, they stop
      incorporating nutrients and survive thanks to the adipocytes content.

PMID- 18089099
TI  - Structure of the ovaries and oogenesis in Cixius nervosus (Cixiidae), Javesella
      pellucida and Conomelus anceps (Delphacidae) (Insecta, Hemiptera, Fulgoromorpha).
AB  - Ovary organization in representatives of two families of Fulgoromorpha, Cixiidae
      (Cixius nervosus) and Delphacidae (Javesella pellucida and Conomelus anceps), was
      examined by light and transmission electron microscopy. Ovaries of studied
      fulgoromorphans consist of telotrophic ovarioles. From apex to base individual
      ovarioles have four well defined regions: a terminal filament, tropharium
      (trophic chamber), vitellarium and pedicel (ovariolar stalk). Tropharia are not
      differentiated into distinct zones and consist of syncytial lobes containing
      multiple trophocyte nuclei embedded in a common cytoplasm. Lobes are radially
      arranged around a branched, cell-free trophic core. Early previtellogenic
      (arrested) oocytes and prefollicular cells are located at the base of the
      tropharium. The vitellarium houses linearly arranged developing oocytes each of
      which is connected to the trophic core by a broad nutritive cord. Each oocyte is
      surrounded by a single layer of follicular cells that become binucleate at the
      beginning of vitellogenesis.

PMID- 18089100
TI  - Structural and functional diversification of follicular epithelium in Coreus
      marginatus (Coreidae: Heteroptera).
AB  - Follicular cells in Coreus marginatus are diversified into two main
      subpopulations of different cell morphology, ultrastructure, distribution of F
      actin and ionic communication between oocyte and follicular cells. Cells forming
      the insert between the operculum and the bottom of the egg envelope and,
      subsequently, a circle of micropylar processes were retarded as compared to the
      developmental advancement of follicular cells in the equatorial part of ovarian
      follicle. Pinocytotic and vitellogenic activity in the ooplasm adjoining the
      insert cells were lower than in other regions. The inhibition of vitellogenesis
      in the neighbourhood of insert cells, which were not in ionic contact with the
      ooplasm, supports the hypothesis that there is a relation between follicular cell
      development and the regional intensity of vitellogenesis in heteropteran ovarian
      follicles.

PMID- 18089101
TI  - Fine structure of spermiogenesis, spermatozoa and spermatophore of Saxidromus
      delamarei (Saxidromidae, Actinotrichida, Acari).
AB  - Ultrastructural details of spermiogenesis, spermatozoa and the spermatophore of
      the early derived actinedid mite Saxidromus delamarei are described. Spermatids
      and mature sperm cells are provided with up to four acrosomal complexes and
      nuclei derivatives (chromatin bodies). Due to this reason, the sperm cells may be
      classified as synspermia, a sperm type found only in some spiders until now. The
      acrosomal complex is composed of a remarkably complicated vacuole and filament.
      Other peculiarities of sperm structure correspond to those found in prostigmatic
      mites, i.e. penetration of the chromatin body by the acrosomal filament and the
      presence of peripheral invaginations of the plasmalemma. The sperm cells are
      covered by a thin secretion layer of probably proteinaceous material. Stalked
      spermatophores are rather large, but simply structured and contain relatively few
      sperm cells. The results are discussed taking systematical and behavioural
      aspects into account. In particular, it is suggested that the peculiar mating
      behaviour of these mites secures both sperm transfer and first male's sperm
      priority and that this allowed reduction of sperm numbers.

PMID- 18089102
TI  - Meiotic drive by the Y-linked D gene in Aedes aegypti (L.) (Diptera: Culicidae)
      is associated with disruption of spermiogenesis, leading to premature senescence
      of spermatozoa.
AB  - Y chromosome meiotic drive in the mosquito Aedes aegypti, due to the gene D
      (Distorter) in coupling with M (male determination) [the MD haplotype], is
      associated with spermiogenic disruption, leading to senescence, at a rate
      proportionate to male excess. Spermiogenesis was compared between 'Enhanced
      Mutant' males with a strongly female-depleted sex ratio (8.9% females), 'Mutant'
      males showing a lesser degree of distortion (38.3% females), and two controls
      with normal sex ratios (51.2% and 49.2% females). Sections of testes dissected
      from mature pupae and adults aged 0, 4, 8, 12 and 16 days were examined by
      transmission electron microscopy. A difference between Mutant and control
      spermiogenesis was apparent as early as the pupal stage when some Mutant
      spermatids showed extra tail elements (axonemes and/or mitochondrial
      derivatives). The same was true of Enhanced Mutant males but to a more extreme
      degree. Sperm senescence was evident in Enhanced Mutant testes from day 0 of
      adult life but in Mutant testes not until day 4. Progressive disorganisation was
      associated with many loose organelles, and disturbance of the anterior-posterior
      axis of gamete differentiation within the testis. Degenerative changes of a
      similar kind in the controls did not become apparent until day 8. These findings
      are discussed with respect to other characteristics of this meiotic drive system,
      in terms of a theory of inhibition of reduction division in spermatogenesis
      associated with fragmentation of the X chromosome, leading to the formation of a
      restitution nucleus as early as metaphase 1.

PMID- 18089103
TI  - Reinterpreting the morphology of the Jurassic scorpion Liassoscorpionides.
AB  - The fossil scorpion (Arachnida: Scorpiones) Liassoscorpionides schmidti Bode,
      1951, the youngest scorpion to be assigned to a putative aquatic clade, from the
      early Jurassic (Toarcian) of Hondelage near Braunschweig, Germany, is
      redescribed. It is the only unequivocal Jurassic scorpion, but there is in fact
      no evidence to support an aquatic mode of life. Some features hint that it might
      be the last of the mesoscorpions-a largely Palaeozoic lineage with a few Mesozoic
      "relict" taxa. Our reinvestigation revealed that the holotype was over
      interpreted by Kjellesvig-Waering. Key characters in his redescription (e.g. eye
      position, chelicerae, gill slits, etc.) are dubious at best and we follow
      previous authors in treating L. schmidti as an incertae sedis species. To
      investigate the hypothesis that mesoscorpions were habitually terrestrial,
      macerated cuticle fragments originally assigned to Mesophonus infans E Wills,
      1947 from the Late Triassic Lower Keuper Sandstone Series of Bromsgrove, UK were
      re-examined. These were drawn as having book lungs in the original description,
      but the original figures are misleading and the expected lung lamellae could not
      be resolved.

PMID- 18089104
TI  - The homology of wing base sclerites and flight muscles in Ephemeroptera and
      Neoptera and the morphology of the pterothorax of Habroleptoides confusa
      (Insecta: Ephemeroptera: Leptophlebiidae).
AB  - The ability to fly is the decisive factor for the evolutionary success of winged
      insects (Pterygota). Despite this, very little is known about the ground-pattern
      and evolution of the functionally very important wing base. Here we use the
      Ephemeroptera, usually regarded as the most ancient flying insects, as a model
      for the analysis of the flight musculature and the sclerites of the wing base.
      Morphology and anatomy of the pterothorax of 13 species of Ephemeroptera and five
      species of Plecoptera were examined and a detailed description of Habroleptoides
      confusa (Ephemeroptera: Leptophlebiidae) is given. A new homology of the wing
      base sclerites in Ephemeroptera is proposed. The wing base of Ephemeroptera
      possesses three axillary sclerites that are homologous to the first axillary, the
      second axillary and the third axillary of Neoptera. For example, the third
      axillary possesses the axillary-pleural muscle that mostly is considered as a
      characteristic feature of the Neoptera. Many of the muscles and sclerites of the
      flight system of the Ephemeroptera and Neoptera can be readily homologised. In
      fact, there are indications that a foldable wing base may be a ground plan
      feature of pterygote insects and that the non-foldable wing base of the
      Ephemeroptera is a derived state.

PMID- 18089105
TI  - Structure and electrophysiological responses of gustatory organs on the
      ovipositor of the parasitoid Leptopilina heterotoma.
AB  - Location, structure and histology of chemosensilla on the tip of the ovipositor
      of the parasitoid Leptopilina heterotoma are described based on SEM and TEM
      studies. Furthermore, we developed a method for recording extracellular action
      potentials from the gustatory neurons in response to host haemolymph. This method
      allowed us to record multi-unit recordings from a sensillum occurring singly on
      the unpaired ovipositor valve. The TEM study of the ovipositor tip revealed the
      presence of six dendrites, the electrophysiological recordings provided evidence
      for the activity of three or possibly four gustatory neurons in response to the
      complex stimulus offered, leaving other taste functions or a mechanoreceptor
      function open for the remaining neurons.

PMID- 18089106
TI  - Homology of the wing base sclerites in Ephemeroptera (Insecta: Pterygota) - a
      reply to Willkommen and Hornschemeyer.
AB  - We revised the homology of wing base structure in Ephemeroptera (Insecta:
      Pterygota) proposed by Willkommen and Hornschemeyer in a recent issue of
      Arthropod Structure and Development. The first free sclerite (s1) in
      Ephemeroptera should be homologized with a part of the first axillary sclerite
      (1Ax) of Neoptera, together with the second free sclerite, whereas the authors
      recognized s1 as a detached part of the anterior notal wing process. The fifth
      free sclerite of Ephemeroptera should be homologized with the median notal wing
      process of Neoptera, rather than it being homologous with a part of 1Ax in
      Neoptera, as the authors postulated. Hypothesized secondary fusion of the
      axillary sclerites in Ephemeroptera and Odonata proposed by the authors is
      premature, because the basal phylogeny of Pterygota is still poorly understood,
      and an alternative interpretation of morphological evolution (i.e., that
      undifferentiated axillary sclerites represent the ground plan of Pterygota) can
      also be drawn from the Ephemeroptera+Neoptera hypothesis.

PMID- 18089107
TI  - Diversity in structural ultraviolet coloration among female sulphur butterflies
      (Coliadinae, Pieridae).
AB  - In some species of sulphur butterflies (Pieridae: Coliadinae) females as well as
      males display bright structural reflectance on their dorsal wing surfaces,
      although comparatively little attention has been paid to this coloration in
      females. We examined the spectral properties of female dorsal coloration and
      scale structure in three species of sulphurs for which published images show
      bright UV reflectance in females: the Neotropical Anteos clorinde and two species
      of Indo-Australian Eurema, E. hecabe and E. candida. In A. clorinde and E.
      hecabe, female UV reflectance is iridescent and produced by thin film
      interference in a system of ridges and lamellae, as it is in conspecific males.
      Female A. clorinde exhibit the same spatial distribution and chromaticity of UV
      reflectance as seen in males, but the UV reflectance in female E. hecabe is much
      smaller in area compared to that of conspecific males and is both less bright and
      less chromatic than observed in males. In contrast, UV reflectance in E. candida
      females is diffuse, and arises from a lack of pterin pigments in the wings, which
      permits a broad-band scattered reflection to be seen. This is the mechanism that
      is known to produce bright UV reflectance in females of the confamilial whites.
      Our results highlight the diversity of UV reflectances and underlying mechanisms
      in sulphurs and suggest multiple evolutionary pathways leading to this diversity
      in female sulphur butterflies.

PMID- 18089108
TI  - The analysis of the mechanosensory origin of the infrared sensilla in Melanophila
      acuminata (Coeloptera; Buprestidae) adduces new insight into the transduction
      mechanism.
AB  - The thoracic infrared (IR) sensilla of the pyrophilous jewel beetle Melanophila
      acuminata most likely have evolved from hair mechanoreceptors (sensilla
      trichodea). To further elucidate the sensory transduction mechanism, the
      morphology of IR sensilla and of neighbouring hair mechanoreceptors was
      investigated by using conventional electron microscopical techniques (SEM, TEM)
      in combination with focused ion beam milling (FIB). It was assumed that any
      deviation from the bauplan of a sensillum trichodeum is of particular concern for
      the transduction of IR radiation into a mechanical stimulus. Thus, the structures
      supposed to be relevant for stimulus uptake and transduction were homologized.
      Compared to a hair mechanoreceptor, an IR sensillum shows the following special
      features: (i) the formation of a complex cuticular sphere instead of the bristle;
      the sphere consists of an outer exocuticular shell as well as of an inner porous
      mesocuticular part. (ii) The enclosure of the dendritic tip of the
      mechanosensitive neuron inside the sphere in a fluid-filled inner pressure
      chamber which is connected with a system of microcavities and nanocanals in the
      mesocuticular part. Hence we propose that an IR sensillum most probably acts as a
      microfluidic converter of infrared radiation into an increase in internal
      pressure inside the sphere which is measured by the mechanosensitive neuron.

PMID- 18089109
TI  - Morphology of testicular and post-testicular spermatozoa in Microstigmus arlei
      Richards, 1972 and M. nigrophthalmus Melo, 1992 (Hymenoptera: Apoidea:
      Pemphredoninae) with phylogenetic consideration.
AB  - The sperm of Microstigmus arlei and Microstigmus nigrophthalmus are twisted in a
      spiral and consist of two regions: the head, formed by an acrosome and a nucleus,
      and the flagellum, formed by two asymmetric mitochondrial derivatives, a long
      centriolar adjunct, an axoneme (9+9+2) and two accessory bodies. The head shows a
      characteristic morphology. The acrosome is very long and is basically made up of
      a paracrystalline structure. In the central head region, the acrosome is inserted
      into the nucleus, which is observed coiling laterally around the paracrystalline
      structure. In the subsequent part of the spermatozoon the nucleus appears round
      in transverse sections, and over some length it is still penetrated by the
      acrosome until shortly distal to the flagellar insertion. At this point the
      nucleus forms an inverted cone-shaped projection. These morphological
      characteristics of acrosome and nucleus of the Microstigmus wasp have not been
      previously described in Apoidea and are useful for phylogenetic evaluation of
      this superfamily.

PMID- 18089110
TI  - The Balbiani body in the oocytes of a common cellar spider, Pholcus phalangioides
      (Araneae: Pholcidae).
AB  - Previtellogenic oocytes of a common cellar spider, Pholcus phalangioides, contain
      a single aggregation of organelles referred here to as the Balbiani body. It is a
      well defined ooplasmic structure predominantly composed of fine granular nuage,
      RNA rich material but comprising also mitochondria, vesicles of endoplasmic
      reticulum and stacks of Golgi cysternae. The Balbiani body originates early
      during previtellogenesis in the form of a cap-shaped mass in juxtaposition to one
      pole of the oocyte nucleus. During later stages of previtellogenic growth the
      Balbiani body translocates as a single body towards the ooplasm periphery. The
      results presented indicate that Balbiani body translocation is cytoskeleton
      independent. Balbiani body repositioning does not result in the localization of
      its components to any distinct, asymmetrically situated region of the ooplasm
      but, instead, ends up with their even dispersion in the oocyte cortex. The
      Balbiani body in Pholcus does not seem to be implicated either in germ cell
      determination or organelle inheritance. Its homology with similar organelle
      accumulations in the oocytes of other species is discussed.

PMID- 18089111
TI  - Spermatozoa and spermiogenesis of Liphistius cf. phuketensis (Mesothelae,
      Araneae, Arachnida) with notes on phylogenetic implications.
AB  - The present study deals with the spermatozoa and spermiogenesis of Liphistius cf.
      phuketensis, a representative of the most primitive and enigmatic spider group
      Mesothelae. The general organization of the spermatozoa is very similar to the
      condition known from Amblypygi supporting a sister-group relationship between
      Araneae and Amblypygi. Besides plesiomorphic characters such as, e.g., an
      elongated and corkscrew shaped nucleus, the sperm cells are characterized by
      several apomorphic characters, e.g., the giant body and conspicuous membranous
      areas which are formed at the end of spermiogenesis. As the transfer form,
      coenospermia are formed at the end of spermiogenesis, which strongly supports the
      idea that this type of sperm aggregation is the primitive transfer form within
      spiders. A very remarkable character of the spermatozoa of some groups of
      arachnids is the coiling of the main cell organelles at the end of
      spermiogenesis. Previously, the Mesothelae were believed to be the only spider
      group which does not show a complete coiling of the main cell organelles. With
      the present study the first evidence of a complete coiling of spermatozoa within
      this primitive spider group could be documented, indicating that this character
      is part of the ground pattern of spider spermatozoa. Consequently, the incomplete
      coiling seems to be a synapomorphy of certain species of Mesothelae, which sheds
      new light on the discussion of the phylogenetic relationships of this group.

PMID- 18089112
TI  - Embryonic development of a peripheral nervous system: nerve tract associated
      cells and pioneer neurons in the antenna of the grasshopper Schistocerca
      gregaria.
AB  - The grasshopper antenna is an articulated appendage associated with the
      deutocerebral segment of the head. In the early embryo, the meristal annuli of
      the antenna represent segment borders and are also the site of differentiation of
      pioneer cells which found the dorsal and ventral peripheral nerve tracts to the
      brain. We report here on another set of cells which appear earlier than the
      pioneers during development and are later found arrayed along these tracts at the
      border of epithelium and lumen. These so-called nerve tract associated cells
      differ morphologically from pioneers in that they are bipolar, have shorter
      processes, and are not segmentally organized in the antenna. Nerve tract
      associated cells do not express horseradish peroxidase and so are not classical
      neurons. They do not express antigens such as repo and annulin which are
      associated with glia cells in the nervous system. Nerve tract associated cells
      do, however, express the mesodermal/mesectodermal cell surface marker Mes-3 and
      putatively derive from the antennal coelom and then migrate to the
      epithelium/lumen border. Intracellular recordings show that such nerve tract
      associated cells have resting potentials similar to those of pioneer cells and
      can be dye coupled to the pioneers. Similar cell types are present in the
      maxilla, a serially homologous appendage on the head. The nerve tract associated
      cells are organized into a cellular scaffold which we speculate may be relevant
      to the navigation of pioneer and sensory axons in the early embryonic antennal
      nervous system.

PMID- 18089113
TI  - Ultrastructure of alimentary tract formation in embryos of two insect species:
      Melasoma saliceti and Chrysolina pardalina (Coleoptera, Chrysomelidae).
AB  - Embryogenesis of the alimentary tract in two chrysomelid species (Chrysolina
      pardalina and Melasoma saliceti) is described. The embryonic development of both
      species lasts 7days at room temperature. Stomodaeum and proctodaeum invaginate at
      the anterior and posterior ends of the germ band. Together with the ectodermal
      tissue the endoderm cells also enter into the embryo. The anterior and posterior
      parts of the alimentary tract wedge into the yolk in the form of conical
      structures. The endodermal cells remain at the yolk surface and start migration
      over the yolk mass as two lateral bands of cells. The endoderm is always
      accompanied by mesoderm. On the fifth day of development the endodermal cells
      together with the mesoderm layer spread over the ventral and dorsal sides of the
      yolk mass and form the single layered primordium of the midgut epithelium. On the
      sixth day of development a basal lamina appears between the endoderm and the
      mesoderm cells and differentiation of both tissues starts. The endodermal
      epithelium cells change shape from flat to cuboidal and eventually into columnar.
      Mesoderm cells differentiate into muscle and tracheae. On the 7thday of
      development stomodaeum and proctodaeum become lined with cuticle and the midgut
      becomes covered with microvilli. The yolk cells populating the yolk mass do not
      contribute to midgut formation in the species studied.

PMID- 18089114
TI  - Possible atavisms of genitalia in two species of earwig (Dermaptera), Proreus
      simulans (Chelisochidae) and Euborellia plebeja (Anisolabididae).
AB  - Male and female genitalia generally show a rapid evolutionary rate, which raises
      the problems related to homologization and the determination of the polarities of
      evolutionary changes. In earwigs (Dermaptera), multiple or branched female sperm
      storage organs (spermathecae) have been reported for members of the
      Karschiellidae, Pygidicranidae, and Diplatyidae, collectively termed the "basal"
      Dermaptera. Whether the complicated spermathecae represent a plesiomorphy or an
      apomorphy has not been resolved. Here I report the occurrence of multiple or
      branched spermathecae in gamma-irradiated samples of two earwig species,
      Euborellia plebeja (Dohrn, 1863) (Anisolabididae) and Proreus simulans (Stal,
      1860) (Chelisochidae), which belong to the "higher" Dermaptera (Apachyidae,
      Labiduridae, Anisolabididae, Spongiphoridae, Chelisochidae, and Forficulidae).
      Females belonging to the higher Dermaptera normally have a single-unbranched
      spermatheca. I discuss examples of possible atavisms in relation to the
      evolutionary pathways of spermathecal morphology. Possible atavisms in the number
      of male organs for sperm transfer (virgae) are also reported.

PMID- 18089116
TI  - A functional analysis of compound eye evolution.
AB  - New data on the phylogenetic relationships of various arthropod groups have
      spurred interesting attempts to reconstruct the evolution of arthropod nervous
      and visual systems. Some of the relevant new data are cell identities and
      developmental processes in the nervous and sensory systems, which is particularly
      useful for reconstructing the evolution of these systems. Here, we focus on the
      structure of compound eye ommatidia, and make an evolutionary analysis with
      functional arguments. We investigate possible routes of evolution that can be
      understood in terms of selection for improved visual function, and arrive at a
      number of conclusions that are discussed in the light of recent phylogenetic
      hypotheses. On the basis of ommatidial focusing structures and the arrangement of
      receptor cells we show that the evolution of compound eyes proceeded largely
      independently along at least two lineages from very primitive ancestors. A common
      ancestor of insects and crustaceans is likely to have had ommatidia with focusing
      crystalline cones, and colour and/or polarization vision. In contrast, the
      compound eyes in myriapods and chelicerates are likely to date back to ancestors
      with corneal lenses and probably without the ability to discriminate colour and
      polarization.

PMID- 18089117
TI  - Furcation, field-splitting, and the evolutionary origins of novelty in arthropod
      photoreceptors.
AB  - Arthropod photoreceptor evolution is a prime example of how evolution has used
      existing components in the origin of new structures. Here, we outline a
      comparative approach to understanding the mutational origins of novel structures,
      describing multiple examples from arthropod photoreceptor evolution. We suggest
      that developmental mechanisms have often split photoreceptors during evolution
      (field-splitting) and we introduce "co-duplication" as a null model for the
      mutational origins of photoreceptor components. Under co-duplication, gene
      duplication events coincide with the origin of a higher level structure like an
      eye. If co-duplication is rejected for a component, that component probably came
      to be used in a new photoreceptor through regulatory mutations. If not rejected,
      a gene duplication mutation may have allowed the component to be used in a new
      structure. In multiple case studies in arthropod photoreceptor evolution, we
      consistently reject the null hypothesis of co-duplication of genetic components
      and photoreceptors. Nevertheless, gene duplication events have in some cases
      occurred later, allowing divergence of photoreceptors. These studies provide a
      new perspective on the evolution of arthropod photoreceptors and provide a
      comparative approach that generalizes to the study of any evolutionary novelty.

PMID- 18089118
TI  - Comments on the eyes of tardigrades.
AB  - A survey is given on the scarce information on the visual organs (eyes or ocelli)
      of Tardigrada. Many Eutardigrada and some Arthrotardigrada, namely the
      Echiniscidae, possess inverse pigment-cup ocelli, which are located in the outer
      lobe of the brain, and probably are of cerebral origin. Occurrence of such organs
      in tardigrades, suggested as being eyeless, has never been checked. Depending on
      the species, response to light (photokinesis) is negative, positive or
      indifferent, and may change during the ontogeny. The tardigrade eyes of the two
      eutardigrades examined up to now comprise a single pigment cup cell, one or two
      microvillous (rhabdomeric) sensory cells and ciliary sensory cell(s). In the eyes
      of the eutardigrade Milnesium tardigradum the cilia are differentiated in an
      outer branching segment and an inner (dendritic) segment. Because of the scarcity
      of information on the tardigrade eyes, their homology with the visual organs of
      other bilaterians is currently difficult to establish and further comparative
      studies are needed. Thus, the significance of these eyes for the evolution of
      arthropod visual systems is unclear yet.

PMID- 18089119
TI  - The nauplius eye complex in 'conchostracans'(Crustacea, Branchiopoda:
      Laevicaudata, Spinicaudata, Cyclestherida) and its phylogenetic implications.
AB  - The nauplius eye in Cyclestherida, Laevicaudata and Spinicaudata (previously
      collectively termed Conchostraca) consists of four cups of inverse sensory cells
      separated by a pigment layer and a tapetum layer. There are two lateral and two
      medial cups, a ventral medial cup and a posterior medial cup. The pigment and
      tapetum layers contain two different kinds of pigment granules, the inner pigment
      layer relatively large, dark (and electron dense) granules, and the outer tapetum
      layer light, reflective pigment granules. The presence of four cups and two
      different kinds of pigment granules are interpreted as autapomorphies of
      Phyllopoda. The position and shape of the nauplius eye in Spinicaudata is very
      distinct and herein interpreted as an autapomorphy of this taxon. Additional
      frontal eyes might be present dorsally or ventrally in varying proximity to the
      nauplius eye, but they have separate nerves from their sensory cells to the
      nauplius eye centre in the protocerebrum. Rhabdomeric structures are present in
      all these frontal eyes, evidencing their light sensitivity. In Lynceus biformis
      and L. tatei (Laevicaudata), two pairs of frontal eyes were found. In
      Cyclestheria hislopi (Cyclestherida), an unpaired ventral frontal eye is present.
      We did not find additional frontal eyes in Limnadopsis parvispinus and
      Caenestheriella sp. (Spinicaudata).

PMID- 18089120
TI  - Stomatopod eye structure and function: a review.
AB  - Stomatopods (mantis shrimps) possess apposition compound eyes that contain more
      photoreceptor types than any other animal described. This has been achieved by
      sub-dividing the eye into three morphologically discrete regions, a mid-band and
      two laterally placed hemispheres, and within the mid-band, making simple
      modifications to a commonly encountered crustacean photoreceptor pattern of eight
      photoreceptors (rhabdomeres) per ommatidium. Optically the eyes are also unusual
      with the directions of view of the ommatidia of all three eye regions skewed such
      that over 70% of the eye views a narrow strip in space. In order to scan the
      world with this strip, the stalked eyes of stomatopods are in almost continual
      motion. Functionally, the end result is a trinocular eye with monocular range
      finding capability, a 12-channel colour vision system, a 2-channel linear
      polarisation vision system and a line scan sampling arrangement that more
      resembles video cameras and satellite sensors than animal eyes. Not surprisingly,
      we are still struggling to understand the biological significance of stomatopod
      vision and attempt few new explanations here. Instead we use this special edition
      as an opportunity to review and summarise the structural aspects of the
      stomatopod retina that allow it to be so functionally complex.

PMID- 18089121
TI  - Eye and optic lobe metamorphosis in the sunburst diving beetle, Thermonectus
      marmoratus (Coleoptera: Dytiscidae).
AB  - Nearly nothing is known about the transition that visual brain regions undergo
      during metamorphosis, except for Drosophila in which larval eyes and the
      underlying neural structure are strongly reduced. We have studied the larvae of
      the sunburst diving beetle, Thermonectus marmoratus (Coleoptera: Dytiscidae),
      which are sophisticated visually oriented predators characterized by six
      elaborate stemmata on each side of the head and an associated large optic lobe.
      We used general neurohistological staining and 3D reconstruction to determine how
      the eyes and optic lobe of T. marmoratus change morphologically during
      metamorphosis. We find that in third (last) instar larvae, the adult neuropils
      are already forming de novo dorsally and slightly anteriorly to the larval
      neuropils, while the latter rapidly degenerate. Larval eyes are eventually
      reduced to distinct areas with dark pigmentation. This complete reorganization,
      which may be an evolutionarily conserved trait in holometabolous insects, occurs
      despite the considerable costs that must apply to such a visually complex animal.
      Our findings are consistent with the concept that stemmata are homologous to the
      most posterior ommatidia of hemimetabolous insects, an idea also recently
      supported by molecular data.

PMID- 18089122
TI  - The fine structure of the eyes of some bristly millipedes (Penicillata,
      Diplopoda): additional support for the homology of mandibulate ommatidia.
AB  - The eyes of adult Phryssonotus platycephalus (Synxenidae) and Polyxenus lagurus
      (Polyxenidae) were investigated by light and electron microscopy. At each side of
      the head, various numbers of eye cups are situated on projections, the eye hills.
      The eye cups of P. platycephalus and P. lagurus are similarly structured and
      considered homologous sense organs. Each corneal lens is biconvex and formed by
      four to six pigmented corneagenous cells with their nuclei displaced towards the
      mid-periphery of the eye cup. The corneal surface displays a conspicuous
      nanostructure of fingerprint-like ridges in P. platycephalus. However, the
      corneal surface appears smooth in P. lagurus. In P. platycephalus. A rudimentary
      crystalline cone is observed in each eye cup, always produced by a constant
      number of three eucone cells. The crystalline cone is wedged between the corneal
      lens and the distal rhabdom and consists of three distinct compartments. Each
      cone compartment is connected to the voluminous proximal nuclear region by one
      elongated cytoplasmic process, which runs through the infraretinular space. A
      dual type retinula is always arranged in two distinct horizontal cell layers. The
      distal retinula contains an unfixed number of four to five cells in P. lagurus,
      whereas it contains five to eight cells in P. platycephalus. The distal retinula
      cells form a large and fused axial rhabdom. A constant number of three proximal
      retinula cells give rise to a small axial rhabdom, which looks more or less
      triangular in cross sections. The basal matrix is rather thin, inconspicuous and
      lines the bases of the eye cups. The ultrastructure of the eye cups of P.
      platycephalus resembles that observed in the ommatidia of the centipede Scutigera
      coleoptrata. The present study lends additional support to the homology of
      mandibulate ommatidia, because of the common possession of crystalline cone cells
      and a bilayered dual type retinula in the eye cups of P. platycephalus. Ommatidia
      or unicorneal eyes that include eucone cells with nuclei displaced outside the
      cone compartments, as found in Scutigeromorpha and Penicillata, might also be
      interpreted as an additional autapomorphy of the Myriapoda. The suggested
      homology of scutigeromorph and penicillate eyes implies that penicillate eye cups
      have to be considered modified, probably miniaturized ommatidia.

PMID- 18089124
TI  - The anatomy and ultrastructure of the suctorial organ of Solifugae (Arachnida).
AB  - Solifugae possess an evertable, adhesive pedipalpal organ (suctorial organ) at
      the tip of the distal tarsus of each pedipalp that is unique among arachnids.
      When inverted inside the pedipalp, the suctorial organ is covered with two
      cuticular lips, a dorsal upper lip and a ventral lower lip, but it can be
      protruded rapidly in order to facilitate grasping prey or climbing on bushes or
      even climbing on smooth surfaces due to its remarkable adhesive properties. In
      this study, the suctorial organs of different species from old world families
      Galeodidae and Karschiidae and new world families Ammotrechidae and Eremobatidae
      were investigated by means of light microscopy, scanning and transmission
      electron microscopy. In all representatives, the suctorial organ is formed by an
      evertable, cuticular pad with a complex internal stabilizing structure. The
      procuticle of this pad consists of a lattice-like basal plate and numerous
      stalked structures connected to this basal plate. The shafts of the stalked
      structures are regularly organized and ramify apically. The surface of the
      suctorial organ is constituted of a very thin epicuticle overlaying the ramifying
      apices forming ridges and furrows on the ventral side of the suctorial organ.

PMID- 18089125
TI  - Morphology of the pretarsus of the sawflies and horntails (Hymenoptera:
      'Symphyta').
AB  - The pretarsal structures have been studied in representatives of 13 families of
      'Symphyta' by means of light microscopy. The pretarsal sclerites (manubrium,
      planta, and unguitractor) vary in shape among different families. The shape of
      the manubrium is triangular in representatives of Xyelidae and Orussidae and
      bifurcated in those of Tenthredinoidea. For representatives of Siricomorpha, an
      elongated shape of the manubrium is typical with such variations, as distally
      expanded, proximally expanded, clavate, spear-shaped. Plantae of different
      Symphyta vary in shape and level of sclerotization. In representatives of
      Siricidae, the female manubrium and arolium are significantly reduced, and arcus
      and dorsal plates are completely absent. Siricid males possess all pretarsal
      sclerites and a well-developed arolium. Auxiliary sclerites are absent in
      representatives of Orussidae. Trichoid sensilla are absent on the plantae in
      representatives of Cephidae and Orussidae. Other studied Symphyta possess two
      trichoid sensilla on the planta. Representatives of all investigated families
      bear two campaniform sensilla on the manubrium, with the exception of Siricidae
      having three sensilla. Kinematics of the pretarsus with bifurcated manubrium are
      modeled and discussed.

PMID- 18089126
TI  - The thorax of Zorotypus (Hexapoda, Zoraptera) and a new nomenclature for the
      musculature of Neoptera.
AB  - External and internal features of the thorax of alate and wingless morphs of
      Zorotypus hubbardi and Z. weidneri were examined and described in detail. Three
      dimensional computer reconstructions were carried out based on microtome section
      series. Skeletal structures are less sclerotised in the wingless specimens and
      the limits of sclerites are indistinct. The alate morphs are almost exclusively
      characterised by plesiomorphic features and their thoracic morphology is probably
      close to the neopteran groundplan. The skeletal structures are very similar to
      the condition found in Plecoptera and the muscle system comprises nearly the
      maximum number known in representatives of Neoptera. Based on the morphological
      investigation of Zorotypus and comparisons with data for other taxa from the
      literature, a new consistent nomenclature for the thoracic muscular system of
      Neoptera is proposed. The few derived features found in the thoracic skeleto
      muscular apparatus of Zorotypus are mostly autapomorphic. The obtained data do
      not clearly indicate the systematic placement of the order. However, the
      arguments for a close relationship with Endopterygota or Dictyoptera,
      respectively, are refuted.

PMID- 18089128
TI  - The pectine organs of the scorpion, Vaejovis spinigerus: structure and
      (glomerular) central projections.
AB  - The pectines of a new-world scorpion were studied as to their sensilla, nerve
      supply, and central nervous projections. (i) Pectines and sensilla in Vaejovis
      are similar to those examined in old-world species previously, although Vaejovis'
      pectines are larger and equipped with more receptors. The specialized peg
      sensilla show ultrastructural features characteristic of arthropod chemo- and
      mechanoreceptors, with the chemosensory exceeding the mechanosensory neuron
      population about 11-fold in number. (ii) The motoneuron supply of the pectines
      resembles that of other limbs and apparently conforms to a general arthropod
      plan. Motoneuron somata occur in three ventral groups, the anterior and posterior
      ipsilateral, and the contralateral groups. (iii) Pectine afferents terminate
      mainly in two ventromedial neuropil areas of the fused subesophageal ganglion
      mass. The larger posterior pectine neuropil shows a distinct glomerular and
      layered ("lobular") organization, reminiscent of insect antennal lobes and
      malacostracan olfactory lobes. Afferents enter the neuropil from its periphery,
      and output neurons leave through a central tract. Most projections show
      somatotopic organization, and several glomeruli exhibit GABA-like
      immunoreactivity, indicative of inhibitory synaptic interactions. The glomerular
      structure of the main pectine neuropil may indicate that such
      compartmentalisation is advantageous for the initial processing of chemosensory
      signals. The somatotopic projection of pectin receptors may be related to the use
      of the pectines in chemosensory orientation to substrate-bound chemicals, and in
      active sensing.

PMID- 18089127
TI  - The fine structure of colleterial glands in two cockroaches and three termites,
      including a detailed study of Cryptocercus punctulatus (Blattaria,
      Cryptocercidae) and Mastotermes darwiniensis (Isoptera, Mastotermitidae).
AB  - The colleterial glands of insects are organs associated with the female genital
      apparatus. In cockroaches, these glands produce secretions that cover two
      parallel rows of eggs during oviposition, and in oviparous species, these
      secretions become the tanned, sculpted, rigid outer casing of the ootheca. The
      goal of this study was to compare the gross anatomy of the colleterial glands and
      the ultrastructure of their component tubules in the phylogenetically significant
      genera Cryptocercus (Blattaria) and Mastotermes (Isoptera). Recent studies
      indicate that cockroaches in the genus Cryptocercus are the sister group of
      termites, and Mastotermes is the only termite known to produce a cockroach-like
      ootheca. One additional oviparous cockroach, Therea, and two additional termites,
      Zootermopsis and Pseudacanthotermes, were also examined. As in other cockroaches,
      the colleterial glands of Cryptocercus and Therea are asymmetrical, with a well
      developed bipartite left gland and a smaller right gland. In the termites
      Mastotermes, Zootermopsis, and Pseudacanthotermes, the colleterial glands are
      composed of a well-developed, paired, anterior gland and a small posterior gland;
      histological staining and cytological evidence suggest that these are homologues
      of the left and the right colleterial glands of cockroaches, respectively. At the
      ultrastructural level, colleterial gland tubules are made of cells belonging to a
      modified class 1 type cell in the cockroaches, in Mastotermes, and in
      Zootermopsis; the latter lays its eggs singly, without a surrounding ootheca-like
      structure. In the advanced termite Pseudacanthotermes, the tubules are made of
      secretory units belonging to the class 3 cell type. This study demonstrates that
      the cytological characteristics of colleterial glands in basal termites are
      similar to those of cockroaches, whether the termite secretes an oothecal casing
      that covers two parallel rows of eggs, as in Mastotermes, or lays its eggs
      singly, as in Zootermopsis. The function of colleterial glands in non
      mastotermitid termites is unknown.

PMID- 18089129
TI  - Sperm structure of Limoniidae and their phylogenetic relationship with Tipulidae
      (Diptera, Nematocera).
AB  - The sperm ultrastructure of a few species of Limoniidae (Limonia nigropunctata;
      L. nubeculosa; Chionea n. sp.; C. alpina; C. lutescens) was studied. The two
      species of Limonia have a monolayered acrosome with crystallized material, a
      three-lobed nucleus in cross section, a ring of centriole adjunct material and a
      flagellum which consists of a 9+9+1 axoneme and a single mitochondrial
      derivative. The central axonemal tubule is provided with 15 protofilaments in its
      tubular wall, while the accessory tubules have 13 protofilaments and are flanked
      by the electron-dense intertubular material. The three species of Chionea share a
      monolayered acrosome, a nucleus with two longitudinal grooves, a centriole
      adjunct material which surrounds the centriole and the initial part of the
      axoneme. The axoneme is of conventional type, with 9+9+2 microtubular pattern,
      with accessory tubules provided with 13 protofilaments and intertubular material.
      However, in C. lutescens the accessory tubules start with 15 protofilaments and
      transform into a tubule with 13 protofilaments. These data are discussed in the
      light of the phylogenetic relationship between Limoniidae and Tipulidae. For this
      purpose, the sperm ultrastructure of Nephrotoma appendiculata was also considered
      comparatively.

PMID- 18089130
TI  - Skeletal adaptations for forwards and sideways walking in three species of
      decapod crustaceans.
AB  - Crustaceans have been successfully employed to study legged locomotion for
      decades. Most studies have focused on either forwards-walking macrurans, or
      sideways-walking brachyurans. Libinia emarginata is a Majoid crab (Brachyura) and
      as such belongs to the earliest group to have evolved the crab form from homoloid
      ancestors. Unlike most brachyurans, Libinia walks forwards 80% of the time. We
      employed standard anatomical techniques and motion analysis to compare the
      skeleton, stance, and the range of motion of the legs of Libinia to the sideways
      walking green shore crab (Carcinus maenas), and to the forwards-walking crayfish
      (Procambarus clarkii). We found animals tended to have greater ranges of motion
      for joints articulating in the preferred direction of locomotion. Leg segments
      proximal to such joints were comparatively longer. Thorax elongation, leg length
      and placement at rest also reflected walking preference. Comparative studies of
      walking in Libinia and other brachyurans may shed light on the neuroethology of
      legged locomotion, and on the anatomical and physiological changes necessary for
      sideways-walking in crustaceans.

PMID- 18089131
TI  - Larval stenocephaly related to specialized feeding in the ant genera Amblyopone,
      Leptanilla and Myrmecina (Hymenoptera: Formicidae).
AB  - Larvae of the ant genera Amblyopone, Leptanilla and Myrmecina have unusually
      minute crania. This characteristic is here termed stenocephaly. To study it in
      detail larvae of the three genera were examined morphometrically and
      histologically in comparison with other non-stenocephalous larvae of the genera
      Cryptopone and Manica. The stenocephalous larvae are very specialized, in that
      their supra- and sub-esophageal ganglia are entirely displaced into the anterior
      thoracic segments, apparently as a consequence of the small cranial capacity. In
      Amblyopone and Leptanilla the small cranium appears to facilitate group feeding
      by a large number of larvae on the whole, intact bodies of the specialized
      centipede prey characteristic of these genera. In Myrmecina, the small, elongate
      head adapts the larva to consume the contents of the partly opened bodies of
      oribatid mites, which are the specialized prey of this genus. Therefore,
      stenocephaly seems to be a larval morphological adaptation facilitating
      specialized predation in these ants. These morphological specializations by ant
      larvae, and active larval involvement in prey dissection are possible because
      ants rear the larvae without confining them in cells. Acellular nests, a
      universal feature in Formicidae, may thus facilitate larval adaptations of
      benefit both to the larvae themselves and to the functionality of parental
      colonies, allowing them more efficiently to exploit accessible prey through well
      integrated cooperation between adult and immature individuals.

PMID- 18089132
TI  - Wing coloration and pigment gradients in scales of pierid butterflies.
AB  - Depending on the species, the individual scales of butterfly wings have a
      longitudinal gradient in structure and reflectance properties, as shown by
      scanning electron microscopy and microspectrophotometry. White scales of the male
      Small White, Pieris rapae crucivora, show a strong gradient in both the density
      in pigment granules and the reflectance. After pigment extraction by aqueous
      ammonia, scales of male P. r. crucivora closely resemble the unpigmented scales
      of female P. r. crucivora. Only a minor gradient exists in the white and orange
      scales of the male Orange Tip, Anthocharis cardamines. Pigment extraction of
      orange scales of A. cardamines causes bleaching. Partial bleaching transforms the
      scales so that they resemble certain scales of Phoebis philea that have a natural
      extreme gradient. Reflectance measurements on an artificial stack of two
      overlapping scales as well as on the scale stacks existing on intact and
      partially denuded wings of the Large White, Pieris brassicae, quantitatively
      demonstrate the reflectance enhancement by scale stacking.

PMID- 18089133
TI  - Building the central complex of the grasshopper Schistocerca gregaria: axons
      pioneering the w, x, y, z tracts project onto the primary commissural fascicle of
      the brain.
AB  - The central complex is a major neuropilar structure in the insect brain whose
      distinctive, modular, neuroarchitecture in the grasshopper is exemplified by a
      bilateral set of four fibre bundles called the w, x, y and z tracts. These
      columns represent the stereotypic projection of axons from the pars
      intercerebralis into commissures of the central complex. Each column is
      established separately during early embryogenesis in a clonal manner by the
      progeny of a subset of four identified protocerebral neuroblasts. We report here
      that dye injected into identified pioneers of the primary brain commissure
      between 31 and 37% of embryogenesis couples to cells in the pars intercerebralis
      which we identify as progeny of the W, X, Y, or Z neuroblasts. These progeny are
      the oldest within each lineage, and also putatively the first to project an axon
      into the protocerebral commissure. The axons of pioneers from each tract do not
      fasciculate with one other prior to entry into the commissure, thereby
      prefiguring the modular w, x, y, z columns of the adult central complex. Within
      the commissure, pioneer axons from columnar tracts fasciculate with the growth
      cones of identified pioneers of the existing primary fascicle and do not pioneer
      a separate fascicle. The results suggest that neurons pioneering a columnar
      neuroarchitecture within the embryonic central complex utilize the existing
      primary commissural scaffold to navigate the brain midline.

PMID- 18089134
TI  - Morphology of the haemolymph vascular system in Tanaidacea and Cumacea: -
      implications for the relationships of "core group" Peracarida (Malacostraca;
      Crustacea).
AB  - Tanaidacea and Cumacea are crucial for understanding the phylogenetic
      relationships of "core group" peracarids. Here, the haemolymph vascular system in
      three tanaidacean and four cumacean species was studied on the basis of
      histological sections and 3D reconstruction. The circulatory organs in Tanaidacea
      include a tubular heart which extends through most of the thorax. It is extended
      into the cephalothorax by an anterior aorta. Haemolymph enters the heart through
      one to two pairs of incurrent ostia. Up to five pairs of cardiac arteries emanate
      from the heart to supply viscera in the body cavity. In the anterior
      cephalothorax, the aorta forms a pericerebral ring from which the arteries for
      the brain and the antennae branch off. In Cumacea, the heart is shorter but more
      voluminous. In all cumaceans studied, five pairs of cardiac arteries supply the
      thoracopods and the pleon. The single pair of ostia is situated in the centre of
      the heart. The anterior aorta runs into the anterior cephalothorax where it
      supplies the brain and antennae. This paper provides a general comparative
      discussion of all available data from the literature and the data provided
      herein. In certain details, the haemolymph vascular system of the Tanaidacea
      resembles that of Amphipoda, and some correspondences between Cumacea and Isopoda
      are pointed out. These findings might support a closer relationship between the
      latter two taxa while they show no support for an amphipod/isopod clade.

PMID- 18089135
TI  - Formation of an egg envelope in the pycnogonid, Propallene longiceps
      (Pycnogonida, Callipallenidae).
AB  - Vitellogenic oocytes of all pycnogonids studied so far contain dilated elements
      of the endoplasmic reticulum, filled with characteristic electron-dense bodies.
      During vitellogenesis these bodies fuse and form larger, almost spherical
      granules that were traditionally interpreted as nascent yolk granules. Here, we
      present the results of ultrastructural investigations of previtellogenic and
      early vitellogenic oocytes of Propallene longiceps (Pycnogonida,
      Callipallenidae). We show that the intra-cisternal bodies/granules of pycnogonids
      are not involved in vitellogenesis but contain macromolecules that are released
      from the oocyte and contribute to the formation of an egg envelope. The obtained
      results are discussed in a phylogenetic context. We suggest that the presence of
      the intra-cisternal electron-dense bodies in the oocyte cytoplasm represents a
      plesiomorphic character of arthropods inherited from the arthropod ancestor.

PMID- 18089136
TI  - Body image: past, present, and future.
AB  - This brief editorial article introduces the new scientific journal, Body Image:
      An International Journal of Research, and describes its rationale and mission in
      relation to the history and future of the study of body image and human
      appearance.

PMID- 18089137
TI  - The (mis)measurement of body image: ten strategies to improve assessment for
      applied and research purposes.
AB  - Body image is a multifaceted construct consisting of a variety of measured
      dimensions. Research in the area has mushroomed in recent years, a phenomenon
      paralleled by an explosion in the assessments developed to measure some aspect of
      the construct. Unfortunately, these developments have not always been guided by a
      clear-cut attention to measurement issues. Assessment errors specific to the
      field of body image and also germane to basic psychological measurement
      strategies have characterized much of the work in the area. This article outlines
      10 such issues with accompanying examples and suggestions for avoiding such
      pitfalls. Attention to these seemingly minor methodological details should result
      in a more consistent conceptualization of body image, utilization of appropriate
      measures in specific contexts, and engender more valid comparisons of findings
      across disparate studies.

PMID- 18089138
TI  - Body image in children and adolescents: where do we go from here?
AB  - During the past two decades, there has been an explosion of research concerning
      body image in children and adolescence. This research has been fueled both by
      concern about the effects of poor body image in children and adolescents
      themselves and by the assumption that body dissatisfaction during childhood and
      adolescence creates risk for the development of body image and eating
      disturbances as well as depression in adulthood. The extant research, however,
      has remained largely descriptive and is marked by methodological problems. The
      purpose of the present paper is to identify substantial gaps in the literature
      concerning body image in children and adolescents. The focus is on four major
      issues: (1) measurement, (2) epidemiological data, (3) developmental trends, and
      (4) the meaning of gender. Addressing these and related questions will aid in the
      development of treatment and prevention programs.

PMID- 18089139
TI  - Body image across the adult life span: stability and change.
AB  - By far, the majority of studies investigating body image in adults have drawn
      samples from college populations within a very narrow age range. The purpose of
      the present paper is to review empirical research on the body image of adults
      older than the typical college student. There are marked changes in appearance
      across the adult life span, especially for women, which lead to the expectation
      of concomitant changes in body image. In fact, the review found that body
      dissatisfaction was remarkably stable across the adult life span for women, at
      least until they are quite elderly. In contrast, the importance of body shape,
      weight and appearance decreased as women aged, underscoring an important
      distinction between evaluation and importance of the body. However, there are
      many large gaps and limitations in the current literature that will need to be
      addressed before a more complete understanding of the development of body image
      across the adult life span is achieved.

PMID- 18089140
TI  - Obesity and body image.
AB  - Modern western culture emphasizes thinness, denigrates excess weight, and
      stigmatizes obese individuals, making it likely that obese people internalize
      these messages and feel badly about the physical presence that brands them. There
      is clear evidence that obesity is linked with poor body image, but not all obese
      persons suffer from this problem or are equally vulnerable. Risk factors
      identified thus far are degree of overweight, being female, and binge eating,
      with some evidence of risk increasing with early age of onset of obesity, race,
      and several additional factors. Treatments do exist for improving body image in
      overweight individuals. Key questions are how to identify those in need of body
      image intervention, how such programs can be integrated with weight loss
      treatments, and ultimately, how body image distress can be prevented.

PMID- 18089141
TI  - The role of body image in the prevention of eating disorders.
AB  - This article reviews theory and research pertaining to prevention of negative
      body image and eating disorders. Research derived from the social cognitive model
      (SCM) and non-specific vulnerability-stressor (NSVS) model indicates that
      sustained prevention effects for attitudes and behaviors are possible, but not
      easy to achieve or explain. These limitations are considered in the context of
      promising research derived from a third model, critical social perspectives
      (CSP). We conclude that (1) research on practice should aim beyond the
      examination of efficacy in order to clarify the active ingredients contributing
      to prevention; and (2) research informed by each of the divergent perspectives
      can be used to enrich theory and practice in the field of eating disorders
      prevention.

PMID- 18089142
TI  - Enhancing quality of life in medical populations: a vision for body image
      assessment and rehabilitation as standards of care.
AB  - This article presents a vision and framework for establishing body image
      assessment and rehabilitation as a standard of care for patients with medical
      disorders. Making this vision a reality depends upon: (1) a thorough
      understanding of the body image construct; (2) application of many new forms of
      body image assessment; (3) refined understanding of body image disorder and
      dysfunction in the context of medical conditions; and (4) a clear plan to
      implement and evaluate prevention, rehabilitation, and treatment programs.
      Applying the many important developments that have occurred in body image theory,
      assessment, and intervention over the past decade holds promise for enhancing the
      quality of life of many individuals with medical conditions.

PMID- 18089143
TI  - Body image and disfigurement: issues and interventions.
AB  - Whether present at birth, congenital or acquired later in life, a visible
      disfigurement can have a profound psychological impact upon the individual
      concerned. Difficulties include adverse effects on body image, quality of life,
      and self-esteem. In addition, social encounters can present many challenges,
      however many individuals adapt to the demands placed upon them and appear
      relatively unaffected by their visible difference. This article reviews current
      literature exploring the psychosocial implications of living with a visible
      difference and considers the complex influence of physical, cultural, and
      psychosocial factors on adjustment. Attempts that have been made to theorise
      individual's experiences, relevant interventions and care provision are then
      examined and the challenges facing researchers in this area are outlined.

PMID- 18089144
TI  - Body image and cosmetic medical treatments.
AB  - Cosmetic medical treatments have become increasingly popular over the past
      decade. The explosion in popularity can be attributed to several factors-the
      evolution of safer, minimally invasive procedures, increased mass media
      attention, and the greater willingness of individuals to undergo cosmetic
      procedures as a means to enhance physical appearance. Medical and mental health
      professionals have long been interested in understanding both the motivations for
      seeking a change in physical appearance as well as the psychological outcomes of
      these treatments. Body image has been thought to play a key role in the decision
      to seek cosmetic procedures, however, only recently have studies investigated the
      pre- and postoperative body image concerns of patients. While body image
      dissatisfaction may motivate the pursuit of cosmetic medical treatments,
      psychiatric disorders characterized by body image disturbances, such as body
      dysmorphic disorder and eating disorders, may be relatively common among these
      patients. Subsequent research on persons who alter their physical appearance
      through cosmetic medical treatments are likely provide important information on
      the nature of body image.

PMID- 18089145
TI  - Advances in a cognitive behavioural model of body dysmorphic disorder.
AB  - Body dysmorphic disorder (BDD) is the most distressing and handicapping of all
      the body image disorders. A cognitive behavioural model of BDD is discussed which
      incorporates evidence from recent studies and advances in the author's 1996
      conceptual model. The model aims to understand the maintenance of symptoms in
      BDD, to assist in the process of engagement of therapy and to guide the
      strategies to use. At the core of BDD is an excessive self-focussed attention on
      a distorted body image, the negative appraisal of such images leading to
      rumination, changes in mood and the use of safety behaviours. Evidence for
      possible risk factors in the development of BDD is also discussed.

PMID- 18089146
TI  - Does body satisfaction differ between gay men and lesbian women and heterosexual
      men and women? A meta-analytic review.
AB  - Studies investigating body image satisfaction among groups of different sexual
      orientations (i.e., gay men, lesbian women, and heterosexual men and women) have
      produced equivocal findings. To synthesise the available research, 27 studies (20
      published and 7 unpublished) were meta-analysed (N=5220). Comparisons between
      heterosexual (n=1397) and gay men (n=984) produced a small effect size, with the
      former being slightly more satisfied with their bodies. An even smaller
      difference was observed for studies comparing heterosexual (n=1391) and lesbian
      women (n=1448), with greater levels of body satisfaction being evidenced by the
      latter group. Tests of homogeneity for each effect size were found to be highly
      significant. In an attempt to identify variables that may be responsible for the
      observed heterogeneity, the following categorical factors were assessed: the
      measures used to evaluate body satisfaction, date of study (1980s versus 1990s+),
      publication status (published or unpublished), and body weight. The results of
      this exploratory search for potential moderator variables as well as limitations
      of the current meta-analysis are discussed.

PMID- 18089147
TI  - Changes in body image during cognitive-behavioral treatment in women with bulimia
      nervosa.
AB  - The purposes of this study were: (1) to examine multidimensional aspects of body
      image of individuals with bulimia nervosa (BN) at pre-treatment, post-treatment,
      and at follow-up, compared to a group of participants without BN; and (2) to
      investigate whether measures of body image predicted outcome at post-treatment
      and follow-up. The clinical sample consisted of 109 females with BN who were
      enrolled in a 12-week cognitive-behavioral group treatment program. Participants
      were assessed at baseline, at the completion of treatment, and at 1- and 6-month
      follow-up visits. The 82 females who comprised the non-bulimic sample were
      assessed at comparable time intervals. At baseline, the participants with BN
      reported greater body dissatisfaction and overestimated body size to a
      significantly greater degree than the comparison group, and reported a
      significantly smaller ideal size relative to perceived size. Results at the end
      of treatment indicated significant improvement in self-reported attitudinal
      disturbance and size overestimation, with continued reductions at follow-up.
      Logistic regression analyses did not demonstrate a predictive relationship
      between body image measures at baseline and outcome at post-treatment or follow
      up, or between post-treatment and follow-up. Implications for treatment include
      specifying the source of body image-related distress and enhancing treatment
      efforts for perceptual and attitudinal aspects of body image.

PMID- 18089148
TI  - Body image and psychosocial differences among stable average weight, currently
      overweight, and formerly overweight women: the role of stigmatizing experiences.
AB  - Substantial research has compared obese and nonobese persons on body image and
      psychosocial adjustment. While differences in body satisfaction are often
      observed, the literature is less clear on other dimensions. Extant differences
      are typically thought to result from the social stigmatization and maltreatment
      experienced by obese persons, especially females. The present study of 165 women
      compared three cohorts who were currently overweight, never overweight, or
      formerly overweight. Relative to never-overweight women, currently overweight
      women reported more body dissatisfaction/distress, overweight preoccupation, and
      dysfunctional appearance investment, as well as more binge eating, lower social
      self-esteem, and less satisfaction with life. Consistent with the "phantom fat"
      phenomenon, formerly overweight women were comparable to currently overweight
      women but worse than never-overweight women on overweight preoccupation and
      dysfunctional appearance investment. Correlations confirmed that, among
      overweight but not formerly overweight women, more frequent stigmatizing
      experiences during childhood, adolescence, and adulthood were significantly
      associated with currently poorer body image and psychosocial functioning.
      Scientific and clinical implications of the findings are discussed.

PMID- 18089149
TI  - Muscularity concerns among men: development of attitudinal and perceptual
      measures.
AB  - The current study reports the development and psychometrics of a figure rating
      scale with leanness and muscularity dimensions and a 13-item questionnaire
      assessing symptoms associated with muscle dysmorphia (MD). Three separate samples
      of men and women completed the muscle dysmorphic disorder inventory (MDDI), the
      bodybuilder image grid (BIG) or both to measure 1-week test-retest reliability,
      internal consistency, convergent and divergent validity and valid placement of
      BIG figures along interval scales of body fat and lean muscle mass. The MDDI and
      MDDI subscales (drive for size, appearance intolerance, and functional
      impairment) had good reliability, internal consistency, convergent and divergent
      validity. The BIG had good to excellent test-retest reliability, good convergent
      and divergent validity and validity as an interval scale. Implications for
      characterizing body image disturbance in men and benefits and limitations of the
      measures are discussed.

PMID- 18089150
TI  - Do men find "bony" women attractive?: Consequences of misperceiving opposite sex
      perceptions of attractive body image.
AB  - Due to its role in the development and maintenance of eating disorders, body
      image perceptions and dissatisfaction continue to be an important area of study.
      Perceptions of attractive body images held by members of the opposite sex are an
      important determinant of body image satisfaction among both men and women. This
      research shows that men are accurate in their perceptions of what women find
      attractive among men, but women believe men want women to be thinner than men
      actually report. Furthermore, this inaccurate perception is associated with
      eating disorder symptomatology. The role of contingent self-worth was also
      assessed. Results indicate that individuals whose self-worth is more contingent
      on appearance-related standards experience more negative consequences than those
      who misperceive what the opposite sex finds attractive, but whose self-worth is
      less contingent on appearance. Implications for intervention are discussed.

PMID- 18089151
TI  - The Sociocultural Attitudes Toward Appearance Questionnaire (SATAQ-3):
      reliability and normative comparisons of eating disordered patients.
AB  - The Sociocultural Attitudes Toward Appearance Questionnaire-3 (SATAQ-3) is a
      measure of one's endorsement of societal appearance ideals. The measure has
      received extensive evaluation in normative samples, but only minimal evaluation
      in clinical groups. In this study, 440 patients with eating disorders completed
      the SATAQ-3. Internal consistencies were excellent for the four SATAQ-3
      subscales. Groups did not differ by diagnosis on the Information subscale,
      however, individuals with bulimia nervosa scored higher than individuals with
      both subtypes of anorexia nervosa (restricting and binge eating/purging) on
      levels of Internalization-General and Internalization-Athlete. The findings
      provide informative normative data, along with preliminary results indicative of
      the potentially greater role of media messages and images in the formation and/or
      maintenance of bulimia nervosa than anorexia nervosa.

PMID- 18089152
TI  - Test-retest reliability and construct validity of Contour Drawing Rating Scale
      scores in a sample of early adolescent girls.
AB  - Test-retest and construct validity of Contour Drawing Rating Scale (CDRS) scores
      were examined in 1056 Grades 7 and 8 girls. Questionnaires were completed four
      times, including retests at 2, 6 and 14 weeks. Test-retest reliability for
      current size, ideal size and current-ideal discrepancy mostly exceeded 0.70 (0.65
      0.87, for the full sample, with higher rs for shorter retest periods). Ideal and
      current size ratings increased slightly over time. High correlations between
      perceived current figure and measured body mass index; moderate rs between
      current-ideal discrepancy and body dissatisfaction and restrained eating; and
      very low or no significant correlations with social desirability supported
      construct validity in this group. The study supported the use of the CDRS in
      early adolescent girls.

PMID- 18089153
TI  - On the methodology of body image assessment: the use of figural rating scales to
      evaluate body dissatisfaction and the ideal body standards of women.
AB  - We examined the use of figural rating scales to measure body dissatisfaction and
      the ideal body standards of women. We also attended to the potential influence of
      demand characteristics in body assessment research using these measures, a
      methodological concern largely ignored in this field. We used both within- and
      between-subjects designs to assess whether women hold different body standards
      for themselves compared to their same sex peers and whether their own ideal body
      size (IBS) is different from what they think men prefer. Regardless of the method
      of data collection (within or between design), we failed to find any differences
      on separate items of body image ideals. The findings do provide evidence of
      robust and large effects for the current-ideal discrepancy as measured by figural
      rating scales, but argue against including multiple questions about ideal body
      preferences on these types of scales. Concerns about the influence of demand
      characteristics were not supported by the data.

PMID- 18089154
TI  - Resisting body dissatisfaction: fat women who endorse fat acceptance.
AB  - Fat women who endorsed fat acceptance (N=128) were recruited from Radiance
      Magazine. Relationships between objectified body consciousness (OBC), body
      esteem, and psychological well-being for the mostly European American sample were
      similar to those found in other samples. OBC was independently related to body
      esteem when weight dissatisfaction was controlled. Those who endorsed the need
      for social change in attitudes towards fat people had higher body esteem and self
      acceptance, and lower body shame, than those who endorsed personal acceptance of
      body size only.

PMID- 18089155
TI  - Body image ups and downs: prediction of intra-individual level and variability of
      women's daily body image experiences.
AB  - This investigation assessed body image states in the context of everyday life
      among 108 college women. Participants initially completed measures of body image
      traits and eating attitudes and subsequently called an automated telephonic
      response system twice daily for 6 days to convey current body image experiences
      on the Body Image States Scale. The research examined the extent to which
      selected pretest variables predicted the level and variability of body image
      states. As hypothesized, less favorable body image state levels were associated
      with lower trait body image satisfaction, more body image dysphoria, more
      dysfunctional investment in appearance, more disturbed eating attitudes, and the
      use of less adaptive and more maladaptive body image coping strategies. Also as
      expected, body image variability was predicted by psychological investment in
      one's appearance, disturbed eating attitudes, and appearance-fixing coping
      strategies. Implications of the results and future research directions are
      discussed.

PMID- 18089156
TI  - An evaluation of the Tripartite Influence Model of body dissatisfaction and
      eating disturbance with adolescent girls.
AB  - The Tripartite Influence Model of body image and eating disturbance proposes that
      three formative influences (peer, parents, and media) affect body image and
      eating problems through two mediational mechanisms: internalization of the thin
      ideal and appearance comparison processes. The current study evaluated this model
      in a sample of 325 sixth through eighth grade girls. Simple path analyses
      indicated that internalization and comparison fully mediated the relationship
      between parental influence and body dissatisfaction and partially mediated the
      relationship between peer influence and body dissatisfaction. Additionally,
      internalization and comparison partially mediated the relationship between media
      influence and body dissatisfaction. Six a priori SEM models based on the full
      Tripartite Influence Model were also evaluated. A resulting model was found to be
      an adequate fit to the data, supporting the viability of the Tripartite Model as
      a useful framework for understanding processes that may predispose young women to
      develop body image disturbances and eating dysfunction.

PMID- 18089157
TI  - Impact of exposure to idealised male images on adolescent boys' body image.
AB  - Research examining the impact on adolescent boys of exposure to muscular,
      athletic, idealised male images has been limited. This research had two aims (i)
      to investigate the mean effect on state body satisfaction and mood of exposure to
      idealised male images in adolescent boys, and, (ii) to identify individual
      attributes that predicted change in state body satisfaction, depression and
      anxiety following image exposure. One hundred and six boys (mean age=15.6 years)
      completed a self-report questionnaire on body image attitudes and psychological
      status. One week later, participants were divided into two groups, one that
      viewed idealised male images (experimental condition) while the other viewed non
      figure advertising images (control condition). Three body satisfaction Visual
      Analogue Scale (VAS), and a depression and anxiety VAS were completed immediately
      prior to and following image exposure. In the experimental compared to control
      condition, there were no significant changes on Want Toned Body, Want to Change
      Body Shape, Depression and Anxiety VAS following image exposure. However, there
      was a significant improvement in Like Body Shape VAS. In the experimental group,
      high internalisation of the muscular, athletic ideal predicted more negative
      response to viewing images on the body image and Depression VAS. Prior body
      dissatisfaction significantly predicted negative response to Body Shape Liking
      and Anxiety VAS. While on average, adolescent boys in this research were not
      negatively affected by exposure to idealised male images, reaction to exposure is
      dependent on individual attributes.

PMID- 18089158
TI  - Body dissatisfaction in married women: the role of spousal influence and marital
      communication patterns.
AB  - Family factors and the media have been established as determinants of body
      satisfaction, yet little research has looked at the contribution of spousal
      influence in body dissatisfaction. Marital quality and satisfaction can be a
      protective factor in the health of women, while high rates of criticism have been
      associated with poorer health outcomes. The present study investigated the
      relationship between perceptions of family and spousal factors and body
      dissatisfaction in married women. Additionally, the impact of marital
      communication was investigated. Seventy-seven married women completed self-report
      questionnaires assessing familial body-focused comments, spousal evaluation of a
      wife's body, marital communication patterns, and body dissatisfaction. After
      controlling for weight status, women's perceptions of familial body-focused
      comments and spousal evaluation emerged as significant predictors of body
      dissatisfaction. It was also found that more destructive communication patterns
      moderated the effect of perceived spousal evaluation on body dissatisfaction.
      This study provides some context for understanding the impact of specific
      influences on women's body dissatisfaction.

PMID- 18089159
TI  - The Body Image Quality of Life Inventory: further validation with college men and
      women.
AB  - The Body Image Quality of Life Inventory (BIQLI) was recently developed to
      quantify both the positive and negative effects of body image on one's
      psychosocial quality of life. The current study was conducted to further validate
      the measure with both men and women and to evaluate its psychometric reliability
      and validity among college students (N=603). Results confirmed that the 19-item
      measure was an internally consistent and unidimensional measure for both sexes. A
      significantly more favorable body image quality of life was reported by men than
      women, by African American than White women, and by women with lower body mass
      indices. Significant body image correlates included body image evaluation,
      investment, and situational dysphoria. A better body image quality of life was
      also related to higher self-esteem, optimism, and social support for both sexes
      and to less eating disturbance among women. The potential utility of this
      construct and unique instrument in further research, especially with medical
      populations, is discussed.

PMID- 18089160
TI  - Body image importance and body dissatisfaction among indigenous Australian
      adolescents.
AB  - Despite their elevated risk of health problems and a propensity to be more
      overweight or underweight relative to the other members of the Australian
      population, there has been no previous investigation of body image concerns among
      Indigenous Australians. In this study we investigated the level of body image
      importance and body image dissatisfaction among 19 rural Indigenous adolescents
      (7 males, 12 females) and 28 urban Indigenous adolescents (15 males and 13
      females). Our hypotheses that there would be gender differences in body image
      importance and body image satisfaction were not generally supported. However,
      males placed more importance on muscle size and strength than females, and rural
      participants placed more importance on weight than urban participants. Comparison
      to existing data obtained from Caucasian adolescents suggested that Indigenous
      youth may be less concerned and dissatisfied with body weight and shape. These
      results are discussed in relation to findings from studies of non-Indigenous
      adolescents, and Indigenous health issues. The limitations of the current study
      and the need for further studies are also discussed.

PMID- 18089161
TI  - The Physical Appearance Ambiguous Feedback Scale (PAAFS): a measure for indexing
      body image related cognitive bias.
AB  - Recent conceptualizations of body image disturbance have included an information
      processing model that includes a focus on an interpretive information processing
      bias. Study 1 involved the development and validation of a measure of appearance
      based cognitive bias, the Physical Appearance Ambiguous Feedback Scale (PAAFS).
      In Studies 2 and 3, two samples of college females (n=313) were tested and the
      psychometric characteristics of the PAAFS were evaluated. Reliability was
      acceptable and convergence with measures of body image and eating disturbance was
      moderate. In Study 4, 313 college females completed the PAAFS in the laboratory
      based on an instructional content designed to induce processing bias. Preliminary
      evidence indicates that the PAAFS appears to be sensitive to instructional set
      manipulations and dispositional level of body dissatisfaction.

PMID- 18089162
TI  - Ideal weight goals of African American women participating in a weight management
      program.
AB  - This descriptive study examined the ideal weight goals of low-income African
      American women enrolled in a weight loss intervention. Prior to treatment, 107
      overweight African American women were weighed, heights were measured, and
      participants completed a self-report measure of various weight-related variables
      (e.g., ideal goal weight, amount lost with previous attempts). The average
      baseline body mass index (BMI) was 38.8kg/m(2). The average ideal BMI was
      27.2kg/m(2), which would require a 29.2% reduction in weight. Ideal weight loss
      was approximately 25kg greater than that achieved during past attempts. Results
      suggest this ethnic minority sample demonstrated satisfaction with achieving an
      ideal weight still classified as overweight. However, the percentage of weight
      loss required to reach such goals is much greater than that recommended by expert
      guidelines. Although future research is needed, weight loss interventionists may
      need to address African American women's acceptance of heavier weight when
      treating their obesity.

PMID- 18089163
TI  - Body esteem and body fat in British school children from different ethnic groups.
AB  - The aim of the study was to examine the relationship between body esteem and body
      fat in British school children. Two hundred and seventy seven, 11-14-year-old
      children from central England took part in the study. Body esteem was measured
      using the Body Esteem Scale for children and percent body fat was determined by
      skin-fold measures. Results indicate that body esteem and adiposity were
      negatively related for the whole sample, for boys and girls and for White
      children, Black children and Asian children. Factorial ANOVA also indicated
      differences in body esteem according to gender and ethnicity. Boys and Black
      children had significantly higher body esteem than girls and Asian children
      respectively. Differences in body fat were also evident according to gender with
      boys being leaner than girls. No differences in body esteem or body fat were
      evident across school years.

PMID- 18089164
TI  - Characteristics and effectiveness of stand-alone body image treatments: a review
      of the empirical literature.
AB  - This literature review examined the characteristics and effectiveness of
      treatments dedicated exclusively to body image. A total of 18 studies met
      selection criteria. All but one involved at least one cognitive-behavioural
      therapy (CBT) condition and only three compared CBT to another treatment
      approach. Twelve studies were conducted with non-clinical, body dissatisfied,
      participants and only one focussed on eating disordered women. Overall, the
      interventions were highly effective in improving body image and psychological
      variables and, to a lesser extent, eating attitude and behaviour. Changes were
      generally maintained at follow-up. Given their efficacy, more controlled trials
      of stand-alone body image treatments in clinical populations are needed.
      Investigating approaches other than CBT may open fruitful avenues of body image
      treatment.

PMID- 18089165
TI  - Body image variability: the influence of body-composition information and
      neuroticism on young women's body dissatisfaction.
AB  - The current studies consider the effect of body size, body composition feedback,
      and the moderating influence of neuroticism (N) on three measures of body
      dissatisfaction (BD) in young women. In Study One, normal-sized subjects who were
      given false feedback indicating that they were either fatter or leaner than
      average showed heightened BD compared to groups who received either accurate or
      no feedback about body size. There was no evidence of a moderating effect of N.
      In Study Two, thinner-than-average subjects who received accurate body-size
      feedback showed greater satisfaction than a control group receiving no
      information. For heavier than average subjects, feedback only increased BD for
      those low on N. Although these results show mixed support for N as a moderator,
      they are the first to show an effect of body composition information on BD.

PMID- 18089166
TI  - Idealized media images and adolescent body image: "comparing" boys and girls.
AB  - Sociocultural theories of body image suggest that body dissatisfaction results
      from unrealistic societal beauty ideals, and one way of transmitting these ideals
      is through the mass media. The present research aimed to examine the effect of
      exposure to images of idealized beauty in the media on adolescent girls' and
      boys' body image. The participants (595 adolescents) viewed television
      commercials containing either images of the thin ideal for women, images of the
      muscular ideal for men, or non-appearance television commercials. Body
      dissatisfaction was measured before and after commercial viewing. It was found
      that exposure to idealized commercials led to increased body dissatisfaction for
      girls but not for boys. Idealized commercials led to increased negative mood and
      appearance comparison for girls and boys, although the effect on appearance
      comparison was stronger for girls. Further, participants high on appearance
      investment reported greater appearance comparison after viewing idealized
      commercials than those less strongly invested in their appearance. The results
      suggest the immediate impact of the media on body image is both stronger and more
      normative for girls than for boys, but that some boys may also be affected.

PMID- 18089167
TI  - Weight-related words associated with figure silhouettes.
AB  - Antifat attitudes and obesity bias are prevalent in Western society; however,
      little is known about the social meanings and connotations of weight-related
      words such as fat, overweight, and obese (e.g., Robison & Erdman, 1998). The
      purpose of this study was to explore college students' perceptions of weight
      related terminology. Participants (n=131) completed a modified figure rating
      scale in which they identified male and female figure silhouettes most associated
      with a variety of weight-related words and personal characteristics.
      Additionally, participants completed a word association task and provided
      definitions of five weight terms. Results indicated that participants grouped
      weight terms into two groupings (i.e., "slender" and "heavy" weight terms) both
      in the figure rating task and in the word association and definition tasks. Both
      male and female participants selected smaller female figure silhouettes for the
      weight terms overweight, large, fat, and normal weight than for the male figure
      silhouettes. Moreover, associations between weight-related words and personal
      characteristics, including normal weight -physically fit and overweight -lazy,
      were found. The results suggest that weight-related words carry with them social
      meanings and values that reflect an "ideology of blame."

PMID- 18089169
TI  - Our first Body Image birthday: a year in review.

PMID- 18089170
TI  - A cross-sectional study of changes in Norwegian adolescents' body image from 1992
      to 2002.
AB  - The present study examines changes in adolescents' body image over a 10-year
      period. Both satisfaction with appearance in general, and satisfaction with
      different aspects of appearance (e.g., face, muscle tone, and weight) are
      considered. We analyzed data from two general population studies of 13-19-year
      old Norwegians, "Young in Norway 1992" (N = 10,460, response rate = 97.0%) and
      "Young in Norway 2002" (N =1 1,371, response rate = 92.3%). These studies used
      identical sampling procedures, data collection procedures, and measures of body
      image. The analyses showed a polarization in adolescents' body image - concurrent
      with an increase in the proportion of adolescents with a very negative body
      image, there was an increase in the proportion of adolescents with a very
      positive body image. The greater proportion of adolescents with a very negative
      body image could partly be explained statistically by the increased body mass
      index (BMI) in the same period. Girls had a more problematic body image than
      boys, both in 1992 and in 2002. Whether the strength of this gender difference
      changed or not depended on the aspect of appearance considered.

PMID- 18089171
TI  - A prospective examination of body image and smoking cessation in women.
AB  - This study prospectively examined body image in a community sample of women
      smokers (N = 141, 89% European-American, M age = 39.5, M BMI = 25.5)
      participating in a 12-week randomized smoking cessation trial. Participants
      completed measures assessing subjective and perceptual aspects of body image.
      Regression analyses showed that subjective body image was predictive of smoking
      rate at the end of treatment. A MANCOVA revealed that perceptual body image (body
      size estimation) significantly predicted smoking cessation. Quitting smoking
      actually worsened body image, although these results were no longer significant
      after controlling for weight gain. Results support the theory that a negative
      body image may hamper cessation attempts. In addition, weight gain during smoking
      cessation may adversely impact body image and lead to an increased risk for
      relapse.

PMID- 18089172
TI  - Perfectionistic self-presentation, body image, and eating disorder symptoms.
AB  - A specific model for eating disorder symptoms involving perfectionistic self
      presentation and two different moderators (i.e., body image evaluation and body
      image investment) was tested. Participants completed measures of perfectionistic
      self-presentation, body image dysfunction, and eating disorder symptoms. Findings
      indicated that all three dimensions of perfectionistic self-presentation were
      associated with eating disorder symptoms. Results also showed that
      perfectionistic self-presentation predicted eating disorder symptoms in women who
      were dissatisfied with their bodies, but that it did not predict eating problems
      in women who liked their bodies and felt there was little or no discrepancy
      between their actual and ideal appearances. Body image investment did not
      moderate the relationship between perfectionistic self-presentation and eating
      disorder symptoms, suggesting that ego-involvement alone is insufficient to
      promote eating disturbance in the context of perfectionism. The importance of
      self-presentation components of perfectionism and specific body image
      difficulties in predicting eating disorder symptoms are discussed.

PMID- 18089173
TI  - Investment in body image among patients diagnosed with or at risk for malignant
      melanoma.
AB  - We examined investment in body image among 48 patients diagnosed with, or at risk
      for malignant melanoma (MM), as well as factors hypothesized as related to
      increased investment, such as gender, perceived stress, mood, fatigue, and
      personality characteristics. Investment in body image was evaluated using the
      Measure of Body Apperception [Carver, C. S., Pozo-Kaderman, C., Price, A. A.,
      Noriega, V., Harris, S. D., Derhagopian, R. S., Robinson, D. S., & Moffat, F. L.
      Jr. (1998). Concern about aspects of body image and adjustment to early state
      breast cancer. Psychosomatic Medicine, 60, 168-174]. Results showed that women
      reported more concerns about physical appearance than men, and patients with MM
      exhibited more concerns about body integrity than at-risk patients. Concerns
      about body integrity were related to more compulsive personality characteristics,
      whereas concerns about appearance were associated with more histrionic
      personality characteristics. Body image investment was related to poorer
      adjustment as indicated by heightened symptoms of fatigue and stress. This study
      suggests that further research on investment in body image in this patient
      population is warranted.

PMID- 18089174
TI  - Media exposure, mood, and body image dissatisfaction: an experimental test of
      person versus product priming.
AB  - In the current study, 138 college females were randomly assigned to four media
      exposure conditions based on the presence or absence of an attractive person
      (fashion model) and the presence or absence of an appearance-related product.
      Outcome measures consisted of visual analogue ratings of multiple body image and
      mood variables. The results revealed a significant main effect for person,
      indicating that the presence of a model increased levels of body dissatisfaction
      and negative mood. No product effect emerged and there was no significant
      interaction between person and product. These findings suggest that the
      appearance priming effect of media exposure on body dissatisfaction and mood is
      specific to a person stimulus, with no additional effect promoted by a generic
      appearance-relevant stimulus.

PMID- 18089175
TI  - Media images of the "ideal" female body: can acute exercise moderate their
      psychological impact?
AB  - Exposure to the media's "ideal" physique increases mood and body image
      disturbance, especially for at-risk women. Because exercise decreases mood and
      body image disturbance, we examined the ability of acute aerobic exercise to
      moderate the negative psychological impact of exposure to media pictures of the
      "ideal" female body. Women reporting high drive for thinness and media
      internalization viewed pictures of either nonphysique or "ideal" physique
      pictures after engaging in 30min of either aerobic exercise or quiet rest.
      Compared to the nonphysique pictures, viewing the physique pictures resulted in
      increased depression and body dissatisfaction. Acute aerobic exercise, however,
      did not moderate the negative mood states elicited by the media images.
      Implications of our results and future directions for research are discussed.

PMID- 18089176
TI  - Women's exposure to thin-and-beautiful media images: body image effects of media
      ideal internalization and impact-reduction interventions.
AB  - Exposure to media images of thin-and-beautiful women negatively affects the body
      image and mood states of young women. However, not all women are equally
      susceptible to these effects. The present experimental investigation with 123
      young college women evaluated the moderating effects of the extent of
      internalization of media ideals. It also examined the preventative impact of two
      brief interventions (i.e., media literacy information with and without a
      dissonance-induction procedure). Results indicated that relative to a control
      group, the exposure to thin-and-beautiful media images adversely influenced the
      state body image of participants with high internalization levels. Media-literacy
      psychoeducation prior to the media exposure prevented this adverse effect. Adding
      a pre-exposure dissonance-induction procedure did not significantly enhance the
      preventative effects relative to psychoeducation alone. These results and their
      implications for the treatment and prevention of body image disturbances are
      discussed in the context of the empirical literature on the media's effects on
      body image.

PMID- 18089177
TI  - Do representations of male muscularity differ in men's and women's magazines?
AB  - Men overestimate the degree of muscularity that is attractive to women, and women
      overestimate the degree of thinness that is most attractive to men. Consistent
      with the thesis that sociocultural input influences such body type preferences
      and beliefs, we postulated that magazines aimed at a male audience would portray
      a more muscular male body ideal than would magazines aimed at a female audience.
      Systematic comparison of popular magazines (Cosmopolitan, Men's Health, Men's
      Fitness, and Muscle & Fitness) revealed that the ideal male body marketed to men
      is more muscular than the ideal male body marketed to women. We introduce the
      Physical Trait Overvaluation Hypothesis, which proposes that gender-specific
      media fuel emphasis on certain body parts in within-gender prestige competitions.
      The resulting competitive escalation creates a disconnect between the preferences
      of one gender and the personal aspirations of the other.

PMID- 18089178
TI  - Body image perceptions among Chinese children and adolescents.
AB  - In order to investigate the body image self-perception and the prevalence of body
      dissatisfaction among Chinese children and adolescents, 9100 children aged 3-15
      years living in four cities completed a questionnaire assessing body image self
      percepts and ideals by figural stimuli. The results indicate that (1) children's
      body ratings started to be significantly related to their BMIs at age 5 and
      correlations increased with age; (2) a wide range of current body sizes was
      chosen by Chinese boys and girls; (3) the ideal body sizes of boys and girls
      selected by boys and girls, respectively, were "boys by boys">"boys by
      girls">"girls by boys">"girls by girls" and (4) the satisfaction, mild
      dissatisfaction, and moderate dissatisfaction rates were 40.1%, 36.4% and 23.5%,
      respectively. Differences as a function of gender and age were identified. It was
      concluded that the prevalence of body dissatisfaction among children and
      adolescents of urban China was striking, and that the Chinese boys were not
      immune to body dissatisfaction.

PMID- 18089179
TI  - Sociocultural influences on adolescent boys' body image and body change
      strategies.
AB  - Society provides messages about how people should ideally look and previous
      research has indicated these messages, both the actual messages provided and the
      perception of the message, influence body image. Research into male body image
      has shown males are concerned with having a lean and muscular body and as such,
      may want to decrease fat and increase their muscles. This paper explored the
      influence of a range of messages from parents, peers, and the media on a number
      of different measures of 362 adolescent boys' body image and body change
      strategies. Specifically, messages about shape, food, exercise, losing weight and
      increasing muscles were explored in relation to satisfaction with weight and
      muscles, and the use of strategies to decrease weight and increase muscles. The
      findings indicated that parental messages were the strongest influence on body
      image and that parents, the media, and to a lesser extent messages from male
      friends were the strongest predictors of body change strategies.

PMID- 18089180
TI  - Female physical attractiveness in Britain and Malaysia: a cross-cultural study.
AB  - Two purported cues to perceived female physical attractiveness are body mass
      index (BMI) and body shape as measured by the waist-to-hip ratio (WHR). This
      study examined the relative contribution of both cues in several culturally socio
      economically distinct populations. Six hundred and eighty-two participants from
      Britain and Malaysia were asked to rate a set of images of real women with known
      BMI and WHR. The results showed that BMI is the primary determinant of female
      physical attractiveness, whereas WHR failed to emerge as a significant predictor.
      The results also showed that there were significant differences in preferences
      for physical attractiveness along a gradient of socio-economic development, with
      urban participants preferring images of women with significantly lower BMIs than
      their rural counterparts. The findings are discussed in terms of evolutionary
      psychological explanations of mate selection, and sociocultural theory, which
      emphasises the learning of preferences for body sizes in social and cultural
      contexts.

PMID- 18089181
TI  - Body dissatisfaction and adolescent self-esteem: prospective findings.
AB  - The aim of the study was to investigate prospectively the direction of the
      relationship between adolescent girls' body dissatisfaction and self-esteem.
      Participants were 242 female high school students who completed questionnaires at
      two points in time, separated by 2 years. The questionnaire contained measures of
      weight (BMI), body dissatisfaction (perceived overweight, figure dissatisfaction,
      weight satisfaction) and self-esteem. Initial body dissatisfaction predicted self
      esteem at Time 1 and Time 2, and initial self-esteem predicted body
      dissatisfaction at Time 1 and Time 2. However, linear panel analysis (regression
      analyses controlling for Time 1 variables) found that aspects of Time 1 weight
      and body dissatisfaction predicted change in self-esteem, but not vice versa. It
      was concluded that young girls with heavier actual weight and perceptions of
      being overweight were particularly vulnerable to developing low self-esteem.

PMID- 18089182
TI  - Acceptance of cosmetic surgery: scale development and validation.
AB  - We conducted a set of four studies with a total of 1288 adult and undergraduate
      women and men to develop the Acceptance of Cosmetic Surgery Scale. These studies
      provide evidence of this scale's reliability, as well as convergent and
      discriminant validity. Initial explorations using this 15-item scale indicate
      that acceptance of cosmetic surgery is negatively related to satisfaction with
      physical appearance and positively related to attitudes about make-up use. The
      acceptance of cosmetic surgery may be more related to fears about becoming
      unattractive than to hopes of becoming more attractive. Cosmetic surgery
      attitudes were positively related to age for women but not for men. The study's
      limitations and implications are discussed.

PMID- 18089183
TI  - The relationships between objective and subjective ratings of disfigurement
      severity, and psychological adjustment.
AB  - Although the role of the objectively and subjectively rated severity of
      appearance problems is often debated, the impact of severity upon psychological
      adjustment has yet to be explored fully. In this study, 400 patients with a range
      of physical differences in appearance were recruited through general plastic
      surgery outpatient clinics and waiting lists. Patients completed the Derriford
      Appearance Scale 24 (DAS24), a measure of psychological distress and behavioural
      dysfunction related to self-consciousness of appearance. Severity in the
      outpatient group was objectively rated by plastic surgeons, and severity amongst
      the waiting-list group was subjectively rated by the patients themselves.
      Multiple regression modelling demonstrated a linear relationship between
      subjective adjustment and severity, with greater perceived severity associated
      with poorer adjustment. Similar modelling demonstrated a weak but statistically
      significant quadratic relationship between objectively rated severity and
      adjustment for normally visible, but not for normally non-visible differences of
      appearance. Moderate, rather than mild or severe objective severity was most
      related to poor adjustment.

PMID- 18089184
TI  - Development and psychometric evaluation of the Male Body Attitudes Scale (MBAS).
AB  - A measure of men's attitudes toward their body (MBAS) was developed and evaluated
      via three independent samples of college men. In Studies 1 and 2, factor analyses
      determined and cross-validated the MBAS's underlying structure. Three factors
      emerged from the items: muscularity, low body fat, and height. Studies 1 and 2
      provided construct (i.e., convergent, concurrent, and discriminant) validity
      evidence for the MBAS total scale and subscales; they were related or not related
      as expected to drive for muscularity, body esteem, internalization of the
      muscular ideal, pressures for muscularity, pressures for thinness, self-esteem,
      body comparison, eating disorder symptomatology, and impression management. Study
      3 revealed that the MBAS total score and subscale scores were stable over a 2
      week period. The internal consistency reliabilities for the total score and
      subscale scores were high across all three studies. The MBAS should prove useful
      for researchers and clinicians interested in men's body image assessment.

PMID- 18089185
TI  - Are cognitive biases associated with body image concerns similar between
      cultures?
AB  - This experimental investigation examined judgment and memory biases associated
      with body image concerns in American and Chinese young adult samples. In Study 1,
      50 American university students (43 female, 7 males) screened into groups high
      and low in self-reported concerns about body size and weight engaged in a
      computer-based experiment involving the evaluation and later recognition of
      randomly presented fat and thin body words and matched control words.
      Participants high in reported body image concerns judged certain kinds of fat
      words more negatively and remembered them more accurately than individuals low in
      perceived body image disturbances. In general, significant group differences
      remained, after controlling for BMI. In contrast, groups did not differ in
      judgment or memory of thin words or control words. This pattern of differences
      was partially replicated in similar groups from the People's Republic of China
      (52 female, 7 male). Cross-cultural comparisons of responses to the subset of fat
      and thin words used in both experiments indicated the American sample evaluated
      fat words more negatively and was faster in responding to fat words than the
      Chinese sample, although there were no cultural differences in responses to thin
      words. Findings support the hypothesis that information-processing biases related
      to body image problems are specific to these concerns within samples from both
      Western and non-Western cultures, albeit cultural differences in responses to fat
      stimuli were also identified.

PMID- 18089186
TI  - Body image and tobacco cessation: relationships with weight concerns and
      intention to resume tobacco use.
AB  - Concern about weight gain after tobacco cessation is a potential barrier to
      quitting tobacco. Few studies, however, have examined the role of body image in
      cessation-related weight concerns and anticipated relapse. This study
      investigated relationships between current body image dissatisfaction,
      anticipated body image dissatisfaction (discrepancy between anticipated post
      cessation body shape and desired body shape), cessation-related weight concerns,
      and intention to resume tobacco with weight gain. Body image dissatisfaction was
      significantly related to cessation-related weight concerns. Participants who
      reported current dissatisfaction with their body image were 2.6 times more likely
      to intend to resume tobacco use with cessation-related weight gain than those
      with no body image dissatisfaction. Individuals with anticipated body image
      dissatisfaction were 3.4 times more likely to intend to resume tobacco compared
      to individuals with no anticipated body image dissatisfaction. Women and normal
      weight individuals with anticipated body image dissatisfaction appear to be at
      particularly high risk for intending to relapse. Results suggest that tobacco
      cessation interventions may need to target concerns about body image as well as
      weight gain.

PMID- 18089187
TI  - Body image and risky sexual behaviors: an investigation in a tri-ethnic sample.
AB  - The impact of negative body image on risky sexual behaviors has not been
      extensively investigated. The present study examined the relationship between two
      aspects of body image, appearance shame and appearance investment, and
      potentially risky behaviors. The study employed a tri-ethnic sample of 1547 women
      seeking services at two family planning clinics. Logistic regression was utilized
      to examine the relationship between potential risk behaviors and shame and
      investment. Results supported that these aspects of body image were significant
      predictors of inconsistent condom use, having multiple sex partners in the past
      year, and having sex after drinking alcohol or using drugs, and that demographic
      variables (e.g., age, marital status, ethnicity) could not fully account for
      these relationships. The importance of future research investigating the
      relationships among body image, perceived relationship security, affect
      management strategies, and risky sexual behaviors is emphasized.

PMID- 18089188
TI  - The norms and stability of new measures of the multidimensional body image
      construct.
AB  - The measurement of the body image construct has become increasingly
      multidimensional. New assessments are available to measure various facets of body
      image functioning: The Body Image Disturbance Questionnaire, Appearance Schemas
      Inventory-Revised, Body Image Coping Strategies Inventory, and Body Image Quality
      of Life Inventory. The present article reports normative data and acceptable
      internal reliabilities across seven completed investigations using these measures
      with female and male college students. Sex differences were examined and found,
      as expected, for most of the measures. In addition, a study evaluated an
      undetermined but essential psychometric property of these facets of the construct
      their test-retest reliability. In a sample of 107 college students, the 2-week
      stability of these measures was found to be acceptable. Several directions for
      future research with these assessments are identified.

PMID- 18089189
TI  - Adult attachment and body satisfaction. An exploration of general and specific
      relationship differences.
AB  - The relationship between general and specific adult relationship attachment and
      body satisfaction was examined in a community sample of 133 women. Participants
      completed measures of body image (body surveillance, body-as-object esteem, and
      body-as-process satisfaction) and general attachment (anxiety and avoidance) and
      then were primed for a romantic partner or close friend relationship, after which
      they completed specific measures of attachment and body satisfaction. General
      attachment results replicated previous research. Specific attachment results
      demonstrated distinct differences both from general attachment and between
      romantic partner attachment and close friend attachment. Attachment independently
      predicted body satisfaction both for general and close friend measures; however,
      in romantic relationships, only body surveillance independently contributed to
      body satisfaction.

PMID- 18089190
TI  - Beyond "healthy eating" and "healthy weights": harassment and the health
      curriculum in middle schools.
AB  - In this paper we use data from interviews conducted with grades 7 and 8 girls to
      explore connections between body-based harassment and girls' body modification
      practices. We discuss how the elementary health curricula fail to consider
      harassment and other cultural factors that influence the body modification
      practices and eating patterns of diverse girls. More specifically, we argue that
      the "healthy eating, healthy weights" approach of the grades 7 and 8 Ontario
      health curriculum has five limitations: (1) it sends contradictory messages; (2)
      it increases anxieties about body weight; (3) it ignores the multiple causes of
      eating problems; (4) it marginalizes issues most relevant to racialized girls;
      and (5) it ignores dilemmas associated with physical development. We conclude
      with suggestions for developing a curriculum on body dissatisfaction and eating
      disorders prevention that considers the various socio-cultural factors
      influencing the range of body monitoring and modifying practices taken up by
      girls.

PMID- 18089191
TI  - The relative contributions of subjective and objective measures of body shape and
      size to body image and disordered eating in women.
AB  - This research explored the relative contributions of subjective perceptions of
      body weight and body shape/proportion, as well as objective measures of body mass
      index (BMI) and waist-to-hip ratio (WHR) to disordered eating, exercise
      involvement, and body image. One hundred and fifty-eight female university
      students completed questionnaires and provided body measurements for this study.
      Although an interaction between BMI and WHR was found for some measures (i.e.,
      Eating Disorder Examination Questionnaire total and subscale scores), results
      indicated that BMI was consistently the better objective predictor of disordered
      eating and body image. Subjective perceptions of body weight and, to a lesser
      extent, body shape, were found to account for the greatest proportion of variance
      in the dependent measures (disordered eating, body esteem, and body
      dissatisfaction). Overall, these results offer more support for sociocultural
      theories emphasizing the importance of thinness for women, than evolutionary
      theories emphasizing the role of WHR.

PMID- 18089192
TI  - The role of self-improvement and self-evaluation motives in social comparisons
      with idealised female bodies in the media.
AB  - This study investigates the effect of social comparisons with media models on
      women's body image based on either self-evaluation or self-improvement motives.
      Ninety-eight women, for whom appearance was a relevant comparison dimension,
      viewed advertisements that did, or did not, feature idealised models, after being
      prompted to engage in self-evaluation or self-improvement comparisons. The
      results indicate that, when focusing on self-evaluation, comparisons with thin
      models are associated with higher body-focused anxiety than viewing no model
      advertisements. In contrast, when focusing on self-improvement, comparisons with
      thin models are not associated with higher body-focused anxiety than viewing no
      models. Furthermore, women's general tendency to engage in social comparisons
      moderated the effects of self-evaluative comparisons with models, so that women
      who did not habitually engage in social comparisons were most strongly affected.
      It is suggested that motive for social comparison may explain previous
      inconsistencies in the experimental exposure literature and warrants more careful
      attention in future research.

PMID- 18089193
TI  - The relationship of body image dissatisfaction to cigarette smoking in college
      students.
AB  - This study examined the association of cigarette smoking status and body image
      dissatisfaction as measured by the Multidimensional Body-Self Relations
      Questionnaire (MBSRQ), in 1575 young adult college students, 18-24 years of age.
      Respondents were current cigarette smokers (N = 482) or never tobacco users (N =
      1093). Smoking status was found to be significantly associated with 5 of the 10
      MBSRQ subscales, with current smokers having lower scores on Fitness Orientation,
      Health Evaluation and Health Orientation (all p < 0.001) and higher scores on
      Appearance Orientation (p = 0.01) and Overweight Preoccupation (p = 0.03)
      compared with never tobacco users. Furthermore, among current smokers, a higher
      number of days smoked in the last 30 days were associated with lower scores on
      all MBSRQ subscales, except Self-Classified Weight. In terms of clinical
      implications, interventions for smoking cessation among college students might
      benefit from inclusion of components for addressing body image dissatisfaction
      and improving health beliefs.

PMID- 18089194
TI  - The experience of body dissatisfaction in men.
AB  - Evidence suggests that the prevalence of body dissatisfaction (BD) is increasing
      amongst men. However, research has commonly examined the phenomenon in
      predominantly female groups. In view of this, the current study used a
      qualitative methodology to explore the experience of BD in men. Semi-structured
      interviews were conducted with 14 men. The data were analysed using
      Interpretative Phenomenological Analysis. Analysis yielded themes across four
      domains (societal, interpersonal, intrapersonal, and social presentation). Whilst
      participants exhibited a range of appearance concerns, there was commonality in
      the processes by which these were experienced and managed. These generic issues
      are the focus of the themes, and could usefully be incorporated into a new
      assessment tool. Findings are considered in relation to existing (cognitive
      behavioural, self-discrepancy, and sociocultural) theories, and implications for
      clinical practice and future research are discussed.

PMID- 18089195
TI  - The Body Appreciation Scale: development and psychometric evaluation.
AB  - Body image has been conceptualized and assessed almost exclusively in terms of
      its negative dimensions. Therefore, a measure reflecting body appreciation, an
      aspect of positive body image, was developed and evaluated via four independent
      samples of college women. Study 1 (N = 181) supported the Body Appreciation
      Scale's (BAS) unidimensionality and construct validity, as it was related as
      expected to body esteem, body surveillance, body shame, and psychological well
      being. Study 2 (N = 327) cross-validated its unidimensionality. Study 3 (N = 424)
      further upheld the construct validity of the BAS, as it was: (a) related as
      expected to appearance evaluation, body preoccupation, body dissatisfaction, and
      eating disorder symptomatology and (b) unrelated to impression management.
      Studies 1 and 3 also indicated that the BAS predicted unique variance in
      psychological well-being above and beyond extant measures of body image. Study 4
      (N = 177) demonstrated that its scores were stable over a 3-week period. All
      studies supported the internal consistency reliability of its scores. The BAS
      should prove useful for researchers and clinicians interested in positive body
      image assessment.

PMID- 18089196
TI  - The effects of trichotillomania disclosure on peer perceptions and social
      acceptability.
AB  - Many individuals with trichotillomania (TTM) do not disclose their condition to
      others. Although disclosure may have beneficial effects, little is known about
      the consequences of it. The purpose of the current study was to examine the
      effects of a brief, simplified preventative disclosure of TTM. Young adults
      (N=225) read one of four vignettes, which varied in a 2 (male versus female
      character)x2 (preventative disclosure of TTM versus nondisclosure) design, and
      answered several questions regarding the character in the vignette. Although some
      potential positive effects of disclosure were found (e.g., reduced likelihood of
      misattribution), some areas of concerns also surfaced. The findings suggest that
      a brief, simplified preventative disclosure of TTM led to an increase in negative
      social perceptions compared to non-disclosure. More specifically, those
      characters that disclosed TTM were evaluated more negatively and more socially
      rejected than those that did not disclose. However, the overall perceptions of
      persons with noticeable hair loss, regardless of disclosure status, were not
      necessarily negative. Implications of the findings, limitations to the study, and
      directions for future research are discussed.

PMID- 18089197
TI  - Individual differences in susceptibility to experimentally induced phantom
      sensations.
AB  - We investigated individual differences in susceptibility to two vibration-induced
      phantom illusions, i.e. illusory arm extension and nose prolongation ("Pinocchio
      illusion"). Vibration was applied to the biceps brachii tendon of 32 healthy
      participants. Susceptibility to the illusions was quantified by vividness ratings
      and by ratings of the amount of illusory position changes of the arm and illusory
      shape changes of the nose. Participants also completed the Perceptual Aberration
      (PA) and the Need for Cognition (NFC) inventories. PA reflects the frequency of
      spontaneously experienced body schema alterations and NFC a person's tendency to
      cognitively structure experiences. PA was positively correlated with
      participants' susceptibility to illusory arm extension and, exclusively for men,
      also to nose elongation. A high NFC was weakly associated with a high
      susceptibility for the Pinocchio illusion. By inference, these findings indicate
      a physiological basis of PA and a cognitive mediation of experimentally induced
      phantom sensations.

PMID- 18089198
TI  - The effectiveness of stand-alone cognitive-behavioural therapy for body image: a
      meta-analysis.
AB  - This meta-analysis examined the effectiveness of stand-alone body image (BI)
      cognitive-behavioural therapy (CBT). Nineteen studies met inclusion criteria. The
      behavioural dimension of BI improves most after BI CBT while the investment
      dimension improves the least. Individuals with clinical BI disturbances improve
      more than do college student samples. Treatments addressing the attitudinal,
      behavioural, and perceptual components of BI are more effective than treatments
      addressing attitude and behaviour only. Therapist-assisted therapy is more
      effective than is self-directed therapy. BI variables improve somewhat more than
      do general psychological variables, while the latter show equivalent improvement.
      Finally, treatment gains are maintained at follow-up. More research is needed to
      better understand and treat the investment dimension of BI.

PMID- 18089199
TI  - A population-based study of body image concerns among urban Chinese adults.
AB  - Using a nationally representative Chinese urban sample of 930 women and 893 men
      aged 20-45 who were married or had a steady sexual partner, this study examines
      the prevalence, risk factors and sequelae of body image concerns. Women's weight
      loss desires begin at modest BMI levels and are more pronounced among youth,
      among people of urban origin, and among the educated. Women also have stronger
      body image concerns if they are single, living in coastal areas, taller or larger
      than their partner, or if their relationship with their partner is poor.
      Moreover, women who perceive themselves as unattractive and who want to lose
      weight report more psychological distress. These findings suggest that China has
      joined the worldwide diffusion of the thin ideal, with negative consequences for
      women.

PMID- 18089200
TI  - A prospective study of factors that lead to body dissatisfaction during
      pregnancy.
AB  - This study examined changes in body image and predictors of body dissatisfaction
      during pregnancy. It was expected that higher levels of depression, social
      comparison tendencies, teasing, societal pressure to be thin and public self
      consciousness would predict body dissatisfaction prospectively. Healthy pregnant
      women (n=128) completed questionnaires on three occasions during their
      pregnancies reporting on a total of four time points: 3 months prior to pregnancy
      (retrospectively reported), in the early to mid-second trimester, the late
      second/early-third trimester, and the latter part of the third trimester. For the
      most part women reported adapting to the changes that occurred in their body;
      however, women were most likely to experience higher levels of body
      dissatisfaction in early to mid-second trimester. Findings related to predictors
      of body dissatisfaction revealed that both social and psychological factors
      contributed to body image changes in pregnancy. Implications of the findings are
      discussed.

PMID- 18089201
TI  - Mind over muscle? Sex differences in the relationship between body image change
      and subjective and objective physical changes following a 12-week strength
      training program.
AB  - This study examined sex differences in body image change and its correlates over
      the course of a 12-week strength-training program. Participants were 28 men and
      16 women (M age=21.6, SD=2.4) who completed pre- and post-intervention measures
      of body image (Body Areas Satisfaction Scale, Social Physique Anxiety Scale, and
      Drive for Muscularity Scale) and subjective and objective assessments of body
      fat, muscularity, and strength. They participated in a 12-week, 5-day/week full
      body progressive resistance training program. Significant body image improvements
      were found for both sexes (p<.05). Correlates of body image change varied
      somewhat between the sexes. For men, body image improvements were correlated only
      with subjective physical changes. For women, body image improvements were
      correlated with subjective physical changes as well as objective increases in
      strength. These results suggest that although men and women derive body image
      improvements from strength training, they may benefit for different reasons.

PMID- 18089202
TI  - Implicit and explicit attitudes toward fatness and thinness: The role of the
      internalization of societal standards.
AB  - Two studies examined restrained and unrestrained eaters' implicit and explicit
      attitudes toward fatness and thinness. Participants completed measures of
      implicit and explicit attitudes toward fatness and thinness (Studies 1 and 2),
      and a measure of the internalization of sociocultural attitudes toward thinness
      (Study 2). Restrained and unrestrained eaters both had strong implicit negative
      attitudes toward fatness, but restrained eaters had stronger negative explicit
      attitudes and beliefs about fatness. Explicit attitudes and beliefs were related
      to the degree of internalization of sociocultural attitudes, and the
      internalization of sociocultural attitudes partially mediated the relation
      between dietary restraint and explicit attitudes. These results suggest that most
      people are aware of societal standards regarding fatness and thinness and have
      developed negative implicit attitudes toward fatness, but that only some people
      (in particular, restrained eaters) have internalized these standards and
      developed negative explicit attitudes toward fatness that they endorse as
      personal beliefs.

PMID- 18089203
TI  - Male physical attractiveness in Britain and Malaysia: A cross-cultural study.
AB  - Three purported cues to perceived male physical attractiveness are the waist-to
      chest ratio (WCR), body mass index (BMI) and the waist-to-hip ratio (WHR). This
      study examined the relative contribution of each cue in several socio
      economically distinct populations. Ninety-five female participants from Britain
      and Malaysia were asked to rate a set of images of real men with known WCR, BMI
      and WHR. The results showed clear differences along a gradient of socio-economic
      development. In urban settings, WCR was the primary component of attractiveness
      ratings, with BMI playing a smaller role and WHR not reaching significance. In
      the rural setting, BMI was the primary predictor of attractiveness, with WCR
      playing a more minor role and WHR not reaching significance. In general, urban
      participants were more reliant on body shape and chose a relatively slim figure
      with an 'inverted triangle' shape; rural participants were more reliant on body
      weight and chose a heavier figure with a less triangular shape. These findings
      are discussed in terms of evolutionary psychological explanations of mate
      selection and sociological theories that emphasise the effect of resource
      scarcity on preferences for body shapes and sizes.

PMID- 18089204
TI  - Psychological management and body image issues in facial transplantation.
AB  - Facial transplantation, although controversial, is proposed as a major advance in
      facial reconstructive surgery, with the first partial transplant having taken
      place in France in November 2005. Although the psychological impact of facial
      transplantation will not be understood until several procedures have been carried
      out, this article examines the psychological issues likely to arise with
      particular reference to body image. A detailed framework for anticipation and
      management of psychological change is proposed. Pre-operative preparation must
      include thorough psychological preparation for the patient and their family. The
      immediate post-operative period is likely to be challenging, and a detailed
      management plan is proposed emphasising early return to function; subsequent
      psychological issues including altered body image, anxiety, shame, depression,
      communication and behavioural avoidance are discussed and a management strategy
      based on cognitive behavioural principles is proposed for the first post
      operative year. Previous discussion frames psychological outcome in terms of
      complication and risk, tending to downplay the potential advantages of a
      successful procedure; the focus of this paper is on ensuring psychological
      adjustment as an inevitable consequence of change.

PMID- 18089205
TI  - The tripartite influence model of body image and eating disturbance: A
      replication with adolescent girls.
AB  - The tripartite influence model of body image and eating disturbance is a recent
      theoretical approach that includes a test of direct (peer, parental, and media
      factors) and mediational links (internalization of societal appearance standards,
      appearance comparison processes) as factors potentially leading to body
      dissatisfaction and eating disturbance. The theory was evaluated in the current
      study in a sample of 391 adolescent females. A structural equation model that
      evaluated the tripartite model replicated previous findings reported by Keery,
      van den Berg and Thompson (2004) [Keery, H., van den Berg, & Thompson, J. K.
      (2004). A test of the tripartite influence model of body image and eating
      disturbance in adolescent girls. Body Image: An International Journal of
      Research, 1, 237-251.]. Additionally, a second model extended these findings,
      suggesting that peer and media influences are more important than parental
      influences. The results are discussed in light of the need for prevention
      programs to incorporate formative influences and mediational processes in the
      construction of intervention strategies.

PMID- 18089206
TI  - Is peer victimization related to body esteem in 10-year-old girls and boys?
AB  - Several studies show that a history of exposure to appearance-related teasing is
      linked to body dissatisfaction. This study extends those findings by examining
      the impact of bullying, and other forms of peer victimization, on different
      aspects of 10-year-old girls' and boys' body esteem. Participants were 960
      Swedish 10-year-olds, 515 girls and 445 boys. Principal results show that social
      exclusion is related to 10-year-olds' evaluations of their general appearance, to
      evaluations of their weight, and to beliefs about how others perceive their
      appearance. Furthermore, bullied girls have poorer body esteem in terms of
      beliefs of how others perceive their appearance than do bullied boys. Appearance
      teasing was associated with girls' poorer body esteem in terms of general
      appearance and beliefs of others views of their appearance. For boys, teasing was
      associated with poorer body esteem on all dimensions. Thus, this study implies
      that a wider range of peer victimization relates to children's negative self
      perceptions than was former known.

PMID- 18089207
TI  - Media literacy as a prevention intervention for college women at low- or high
      risk for eating disorders.
AB  - This study examined whether the media literacy program, ARMED, is an effective
      prevention intervention for college women at low- or high-risk for an eating
      disorder. Changes in eating disorder risk factors were assessed in low- (n=26)
      and high-risk (n=19) women participating in a two-session media literacy
      intervention as compared to low- (n=31) and high-risk (n=16) controls. Women at
      high-risk for an eating disorder reported significant decreases in body
      dissatisfaction, drive for thinness, feelings of ineffectiveness, and
      internalization of societal standards of beauty after participating in ARMED,
      whereas control participants did not. No significant decreases in perfectionism,
      physical appearance comparisons, or awareness of societal standards of beauty
      were reported among high-risk participants. Changes in eating disorder risk
      factors were not found among low-risk participants, regardless of treatment
      condition. Findings suggest that media literacy may be an effective secondary
      prevention intervention for eating disorders.

PMID- 18089208
TI  - Raising the bar on the body beautiful: An analysis of the body image concerns of
      homosexual men.
AB  - Research suggests that gay men are at particular risk for body image
      dissatisfaction. This study seeks to extend research on gay men's body image
      concerns. A survey assessed the nature and correlates of body image
      dissatisfaction among 64 gay men. The survey included assessments related to
      involvement in and perceived acceptance within the gay community, social
      comparison tendencies, body image satisfaction, self-esteem, and depression. The
      results indicate that most participants were concerned with muscularity rather
      than weight. Greater social comparison tendencies and higher body mass index
      (BMI) were associated with greater body dissatisfaction. Although involvement and
      perceived acceptance in the gay community did not independently predict general
      body image dissatisfaction, there is evidence to suggest that the association
      between body image and self-esteem may be moderated by integration into the gay
      community, defined as involvement and perceived acceptance. Implications for the
      further study of gay men's body image are discussed.

PMID- 18089209
TI  - Effects of a 6-week aerobic dance intervention on body image and physical self
      perceptions in adolescent girls.
AB  - Research examining the impact of physical activity on body image dissatisfaction
      and physical self-perceptions has been both limited and equivocal. The current
      research investigated the effects of 6-week aerobic dance on these variables with
      50 British schoolgirls aged 13-14 years. A cross-over design was used with two
      equivalent groups taught normal physical education and aerobic dance in a
      different order. The Body Attitude Questionnaire (BAQ) and Children and Youth
      Physical Self-Perception Profile (CY-PSPP) were administered as pre, mid and post
      test to each participant in each group before the first intervention, at the
      change over and after 12 weeks. The results of this study revealed that
      participation in 6 weeks of aerobic dance significantly reduced body image
      dissatisfaction (Attractiveness, Feeling Fat, Salience and Strength and Fitness)
      and enhanced physical self-perceptions (Body Attractiveness and Physical Self
      Worth), although these improvements were not sustained. The implications and
      future research directions are discussed.

PMID- 18089210
TI  - Body image and size perceptions of Mexican American women.
AB  - Purpose was to examine in Mexican American women the influences of age, weight,
      socioeconomic status and acculturation level on body image, perceptions of
      attractive and acceptable female shapes, and tolerance for overweight and
      obesity. Participants were 276 Mexican American women. Age, body mass index,
      socioeconomic status, and acculturation level were measured. The Figure Rating
      Scale was used to assess body image, preferences for body size, and perceptions
      of underweight to obese and acceptable body sizes. Significant effects for
      acculturation level and current weight were found. Women who were more Anglo
      oriented showed greater preference for thinner figures. As compared to normal
      weight women, obese women chose larger figures as ideal, realistic, attractive,
      and thinnest acceptable. Findings point to the impact of acculturation and
      obesity on body image and size perceptions. Health professionals working with
      Mexican Americans should consider each individual's current weight and level of
      acculturation.

PMID- 18089211
TI  - Size of drawings influences body size estimates by women with and without eating
      concerns.
AB  - Research has inconsistently shown that women, particularly those with eating
      concerns, inaccurately estimate their body size. In the present study, drawings
      of female bodies, ranging from emaciated to obese, were presented to women with
      and without eating concerns. Drawings approximated the women's actual height or
      were reduced (15.7cm). Women selected the drawing that represented how they
      thought they looked (cognitive rating), felt they looked (affective rating), and
      would like to look (desired rating). Women tended to select larger drawings when
      reduced-size drawings were used. Participants with eating concerns overestimated
      their body size and were more dissatisfied with their body size than participants
      without eating concerns. Size of drawings and the presence of eating concerns did
      not affect ratings of the size of a neutral object. Women did not demonstrate a
      generalized problem in estimating size. Overestimation of body size may be
      exaggerated in research that used reduced-size drawings.

PMID- 18089212
TI  - Change in sociocultural ideal male physique: An examination of past and present
      action figures.
AB  - The physical dimensions of five contemporary action figures were measured and
      compared to their original counterparts to determine whether their physiques have
      become more muscular from their original designs. The circumferences of the neck,
      chest, arm, forearm, waist, thigh, and calf were measured three separate times
      using a Scale Master II model 6325. The mean score was then used in subsequent
      analyses. Except for the waist, it was determined that the body parts of current
      action figures were significantly larger when compared to those of their original
      counterparts. The results of this study indicate that action figures have become
      more muscular and larger over the last 25 years. Furthermore, the increase in
      action figure dimensions may contribute to the multifactoral development of an
      idealized body type that focuses on a lean, muscular physique. This occurrence
      may particularly influence the perceptions of preadolescent males.

PMID- 18089213
TI  - A test of the moderating role of importance of appearance in the relationship
      between perceived scar severity and body-esteem among adult burn survivors.
AB  - This study tested the hypothesis that the relationship between subjective burn
      scar severity and body-esteem is moderated by importance of appearance. Three
      hundred and forty-six adult burn survivors completed a mailed or online survey.
      The three subscales of the Body-Esteem Scale for Adolescents and Adults (BE
      Appearance [satisfaction with general appearance], BE-Weight [weight
      satisfaction], BE-Others [others' evaluations of one's body and appearance]) were
      regressed onto sex, subjective burn scar severity, importance of appearance and
      their two- and three-way interactions. With one exception, the hypothesized main
      effects were significant in each of the regression equations. As hypothesized,
      importance of appearance moderated the relationship between subjective burn scar
      severity and body-esteem for BE-Appearance and BE-Other but not BE-Weight. The
      results of this study are consistent with the cognitive model of body-esteem.
      Clinical implications are discussed.

PMID- 18089214
TI  - Mothers' attitudes toward fat, weight, and dieting in themselves and their
      children.
AB  - We examined how a mother's view of her body, and fatness in general, affects her
      attitude toward her child's weight and eating. Mothers (N=118) of 3-5-year-old
      children filled out a questionnaire designed to assess weight satisfaction, anti
      fat attitudes, and how concerned and restrictive they are with regards to their
      child's weight and eating. We found mothers who were more fearful of being or
      becoming overweight themselves worried more for their children, although fearful
      attitudes did not predict restricting a child's eating. These results suggest
      that maternal attitudes toward their own weight affect their beliefs about their
      children's weight.

PMID- 18089215
TI  - The relationship of drive for muscularity to sociocultural factors, self-esteem,
      physical attributes gender role, and social comparison in middle school boys.
AB  - This study examines the relationship of three sociocultural factors-media
      influence, peer teasing, and parent teasing/comments and three potential
      moderator variables-self-esteem, social comparison, and endorsement of male
      strength and athleticism-to drive for muscularity in middle school boys. There
      were 287 seventh and eighth grade boys who completed a questionnaire measuring
      these variables as well as body mass index (BMI) and pubertal status. Results
      indicated that media influence and male physical attributes endorsement were
      particularly important correlates of drive for muscularity. These findings have
      implications for programs designed to prevent body dissatisfaction among
      adolescent boys.

PMID- 18089216
TI  - Psychometrics properties of the Swansea Muscularity Attitudes Questionnaire
      (SMAQ).
AB  - The psychometric soundness of the Swansea Muscularity Attitudes Questionnaire
      (SMAQ) was examined using two independent samples of Canadian male post-secondary
      students (Ns=250 and 310, respectively). Exploratory and confirmatory factor
      analyses suggested that the final 19-item version of the SMAQ is represented by
      three latent constructs, which we have labeled: intention to become more muscular
      (eight-items), positive attributes of muscularity (nine-items), and engagement in
      muscle-building activities (two-items). Alpha coefficients for the intention and
      positive subscales were very good (i.e., range=.86-.92). Correlation coefficients
      between the two-items comprising the engagement subscale also suggest that they
      can be combined into a composite measure (rs=.70 [study 1] and .58 [study 2]).
      Various tests of criterion-related and construct validity were conducted, with
      results indicating that the SMAQ subscales are valid indicants of the drive for
      muscularity.

PMID- 18089217
TI  - The relationship between the drive for muscularity and anthropometric measures of
      muscularity and adiposity.
AB  - Researchers have found consistently positive associations between women's body
      dissatisfaction and the desire to be thin and anthropometric indices of the
      amount of body fat they care on their frame. However, with the increasing
      emphasis being given to men's body image concerns, such as the drive for
      muscularity, it is important to study the relationship between men's desire to
      become more muscular and the actual amount of muscle they carry on their frames.
      That is, because men who want to become muscular can achieve that through
      strength training, do those with a high drive for muscularity have a high level
      of muscle mass? We explored this issue in a sample of 100 college-aged men and
      found that only one of four anthropometric measure of muscularity (flexed bicep
      circumference) was predictive of engaging in muscularity-oriented behaviors,
      while none predicted attitudes about becoming more muscular. These findings
      suggest either that men's drive for muscularity is unrelated to their actual
      level of muscularity or that current anthropometric indices are not accurate
      enough for a significant relationship to emerge. Suggestions for future research
      and study limitations were discussed.

PMID- 18089218
TI  - Effects of exposure to muscular and hypermuscular media images on young men's
      muscularity dissatisfaction and body dissatisfaction.
AB  - This study examined the effects of exposure to muscular and hypermuscular media
      images on young men's body images, and the moderating roles of baseline body
      dissatisfaction (BD) and muscularity dissatisfaction (MD). Men (M age=21.9,
      SD=2.8) were exposed to pictures of muscular (n=34) or hypermuscular (n=29) male
      physiques throughout a 30-min health seminar. In support of the study hypotheses,
      higher levels of baseline BD and MD were associated with greater post-seminar BD
      and MD. In addition, MD moderated the effects of the exposure conditions on BD;
      greater baseline MD was associated with greater post-seminar BD, but only among
      men who viewed the muscular images. These results speak to the importance of pre
      existing muscularity concerns in determining men's reactions to muscular physique
      images, and suggest that exposure to the media ideal of muscularity, and not
      muscularity per se, elicits body dissatisfaction in men with pre-existing
      muscularity concerns.

PMID- 18089219
TI  - Accuracy of body size estimation: Role of biopsychosocial variables.
AB  - This study evaluated factors related to the perceptual disturbances of body
      image. Using a digital body image computer program, 191 participants (107 women,
      82 men) adjusted an image of their body to the perceived actual size at five body
      regions; chest, waist, hips, thighs and calves. A neutral object (a vase) was
      also adjusted to partial out the level of perceptual distortion present with a
      neutral object. Men and women overestimated the size of the neutral object and
      their body image. Among women, overestimation was primarily predicted by high
      levels of depression, and media and peer influences to be thinner and increase
      muscles. Among men, overestimation was predicted by high BMI, media influences to
      lose weight and increase muscles, and peer influences to increase muscles. These
      findings suggest that perceptual accuracy of body image is primarily predicted by
      biopsychosocial influences.

PMID- 18089220
TI  - Evidence that ideal and attractive figures represent different constructs: A
      replication and extension of Fingeret, Gleaves, and Pearson (2004).
AB  - Figure rating scales are commonly used to measure body dissatisfaction through
      discrepancy indexes (e.g., difference between current and ideal body) and recent
      methodological work by Fingeret, Gleaves, and Pearson suggests that distinctions
      between referent bodies (e.g., ideal or most attractive) are unnecessary. The
      purpose of the current study was to replicate these findings using both male and
      female figure rating scales and an opposite-sex comparison group. We examined the
      relationship between three referent figures (Ideal, Most Attractive to the
      Opposite Sex, and Most Attractive) and attractiveness attributions in 365
      undergraduate men (n=164) and women (n=201). Results suggested that referent
      figures were associated with different attractiveness attributions for both male
      and female figures, but physical characteristics differed only in male figures.
      The impact of referent bodies on discrepancy indexes was also explored.
      Considerations for future research using figure rating scales are discussed.

PMID- 18089221
TI  - Self-objectification and compliment type: Effects on negative mood.
AB  - The effects of trait self-objectification and compliment type
      (Neutral/Character/Appearance) on women's negative mood was examined. One hundred
      and eighty-five undergraduate women participated in mock appearance evaluations
      and interviews before completing questionnaires. As in previous research, women
      high on trait self-objectification displayed substantially greater body shame and
      appearance anxiety than women low on trait self-objectification. Women high on
      trait self-objectification who received character or appearance compliments
      expressed less negative mood than those receiving neutral compliments. A
      supplementary study (N=53) suggested that the effect of positive compliments may
      be due, in part, to the fact that the self-esteem of high trait self-objectified
      participants was largely contingent on others' approval. Offering highly trait
      self-objectified women positive statements concerning either their characters or
      their appearance temporarily assuages negative mood.

PMID- 18089222
TI  - Rates of abuse in body dysmorphic disorder and obsessive-compulsive disorder.
AB  - Body dysmorphic disorder (BDD) continues to challenge professionals due to
      symptom severity, co-morbidity, suicidal ideation, and overvalued ideation.
      Despite the disorder's severity, little research exists. Clinical observation
      suggests a noteworthy history of abuse; therefore the present study investigated
      the reported rate of physical, sexual, and emotional abuse in BDD patients. OCD
      patients were chosen as a comparison group because BDD is considered to be an
      obsessive-compulsive spectrum disorder. A group survey design was used (N=50 for
      each group). Results show significantly higher levels of emotional and sexual
      abuse in the BDD sample versus the OCD sample. No significant differences were
      found in physical abuse. Abuse may be a contributing factor in BDD, but not in
      OCD.

PMID- 18089223
TI  - An investigation of appearance motives for tanning: The development and
      evaluation of the Physical Appearance Reasons For Tanning Scale (PARTS) and its
      relation to sunbathing and indoor tanning intentions.
AB  - Motives for UV exposure have been shown to be related to appearance concerns, yet
      little research has examined specific tan appearance attitudes. Given this
      lacuna, Study 1 involved the identification of six factors among college female
      tanners: general attractiveness, media influence, family/friends influence,
      physical fitness appearance, acne reasons, and skin aging concerns. In Study 2, a
      separate sample of college female tanners were used to validate a higher order
      factor model, which demonstrated acceptable fit. Additionally, the factors
      converged in the expected directions, with the general attractiveness and skin
      aging concerns being the best correlate of UV exposure and sun-protection
      intentions. The relevance of these findings to skin cancer prevention is
      discussed.

PMID- 18089224
TI  - Comparing to perfection: How cultural norms for appearance affect social
      comparisons and self-image.
AB  - Theory and research suggests that cultural norms for appearance present
      unrealistic standards of beauty which may contribute to women's body
      dissatisfaction. In Study 1, women described their appearance more negatively
      than men and made more upward social comparisons about their bodies, but not
      about other domains. Women also compared more than men with unrealistic targets
      (e.g., models). In Study 2, we explored the role of cultural norms for appearance
      in social comparisons with relevant (peer) or irrelevant (model) superior
      targets. When cultural norms were not salient, participants judged a peer to be
      more relevant, compared more with the peer, and were more negatively affected by
      the peer. However, when cultural norms were salient, participants judged a
      professional model to be equally relevant, compared more with the model and felt
      worse after exposure to the model. We discuss the powerful role of cultural norms
      in determining social comparison processes and self-appraisals.

PMID- 18089225
TI  - Cultural representations of thinness in women, redux: Playboy magazine's
      depiction of beauty from 1979 to 1999.
AB  - Playboy's portrayal of the male ideal of feminine beauty, in terms of overall
      body size, percent normative weight, and waist-to-hip ratios (WHRs), was analyzed
      for the years 1979-1999. Trends were examined through body measurements obtained
      from Playboy centerfolds. Results reveal a continuation of the low body mass
      index (BMI) found in the Playmates by earlier studies; however, for the 21 years
      examined, the trend towards increasing thinness seems to have stabilized and may
      have begun to actually reverse. There was also an increase in the centerfolds'
      WHRs over the 21-year time period. Overall, the results support the continued
      valuing in American society of a thin ideal for women; while the images of beauty
      have become somewhat heavier over the 21-year period reviewed, the Playmates
      remain markedly below weights normative for their age group.

PMID- 18089226
TI  - The effects of exposure to feminist ideology on women's body image.
AB  - Body image disturbance has become a common problem among women and there is a
      need to focus on creating empirically supported treatments. Psychoeducational
      interventions have reduced body image dissatisfaction, but their impact is
      limited because they do not offer women adaptive methods of interpreting the many
      appearance-related messages they receive. This study examined if exposure to a
      feminist perspective may provide alternative interpretations of cultural
      messages, thereby increasing body image satisfaction. Participants were randomly
      assigned to a feminist or psychoeducational intervention, or a control group.
      Exposure to the feminist condition resulted in increased self-identification as a
      feminist and greater appearance satisfaction, and changes in feminist identity
      were related to positive changes in body image. The findings indicate that
      exposure to feminist theories may serve as an effective intervention strategy.

PMID- 18089227
TI  - Fat talk and self-presentation of body image: Is there a social norm for women to
      self-degrade?
AB  - The current investigations build upon previous ethnographic research, which
      identified a social norm for adolescent females to engage in "fat talk" (informal
      dialogue during which individuals express body dissatisfaction). In Study 1,
      participants were shown a vignette involving women engaging in fat talk dialogue
      and were subsequently asked to chose one of three self-presentational responses
      for a target female: (1) self-accepting of her body, (2) providing no
      information, or (3) self-degrading about her body. Male and female participants
      believed the target would be most likely to self-degrade, and that this would
      lead women to like her, while the self-accepting response would lead men to like
      her most. Study 2 used the same vignette but participants were asked to respond
      in an open-ended fashion. Participants again expected the target female to self
      degrade. The present findings suggest college students perceive fat talk self
      degradation of body image as normative.

PMID- 18089228
TI  - Appearance-related commentary, body image, and self-esteem: Does the distress
      associated with the commentary matter?
AB  - Research that has examined the association between appearance-based commentary
      and body image has generally focused on the frequency of occurrence of the
      commentary, not the subjective rating of the distress associated with the
      feedback. The current study examined both frequency and distress (effect)
      components of commentary in a sample of 246 undergraduate female students aged 18
      25. Significant correlations were found between both frequency and effect
      dimensions of commentary and measures of body image disturbance and self-esteem.
      The utility of both frequency and effect variables in predicting body image
      disturbance and self-esteem was demonstrated in regression analyses. Implications
      of the findings for broadening the assessment of appearance-based commentary to
      include both dimensions of the construct are discussed.

PMID- 18089229
TI  - The interplay of personality and negative comments about appearance in predicting
      body image.
AB  - This study investigates how personality traits in combination with frequency of
      and emotional reaction to negative comments about appearance while growing up are
      related to appearance evaluation and orientation among adult women. Nine hundred
      and seven participants from a representative sample of Norwegian women aged 22
      55, answered questions measuring body image, personality (Big Five), and history
      of experiencing negative comments about appearance. Results indicated that only
      emotional reaction to negative comments about appearance significantly predicted
      both appearance evaluation and orientation, while frequency of negative comments
      did not. Being extrovert predicted more positive appearance evaluation and being
      more appearance oriented than being introvert. Scoring high on neuroticism was
      related to negative appearance evaluation and high appearance orientation. The
      findings demonstrate the importance of differentiating between the frequency and
      the emotional impact of teasing as well as including personality traits when
      studying body image.

PMID- 18089230
TI  - Body image attitudes and concerns among indigenous Fijian and European Australian
      adolescent girls.
AB  - Research on body image has primarily been conducted among Western women who
      highly value the thin ideal body size. There has been limited research that has
      examined body image attitudes among Fijian adolescent girls who are exposed to
      both traditional sociocultural pressures that promote a larger body size and
      Western pressures that promote slimness. Using in-depth semi-structured
      interviews, we examined the factors associated with body image attitudes and
      concerns among a sample of 16 indigenous Fijian and 16 European Australian
      adolescent girls aged between 13-18 years. An inductive analysis of girls'
      responses indicated that both groups of girls experienced body image concerns
      including body dissatisfaction, a preference for thinness and concerns associated
      with weight gain. These findings have implications for our understanding of the
      role of culture in shaping body image among girls and may prove useful in the
      development of future survey research that can be implemented among both Fijian
      and Western adolescents.

PMID- 18089231
TI  - Weight and health status of inner city African American children: Perceptions of
      children and their parents.
AB  - Poor socioeconomic status and African American (AA) ethnicity contribute to an
      increased risk of obesity for many inner city children. One hundred and forty six
      AA children and 108 AA parents attending an inner city health fair completed
      surveys regarding perceptions of their own (or their child's) weight and the
      impact of weight on health. The children were measured and their body mass
      indexes were calculated. Thirty-seven percent of the child respondents (n=52)
      were at risk of overweight or overweight; of these, 67% perceived themselves as
      normal weight, and 77% thought their weight was healthy. Weighing more was felt
      to be healthy by 17% of children and 29% of parents. Of 39 parents whose children
      were at risk of overweight or overweight, 68% felt their child's weight was
      normal and 80% thought it was healthy. These results suggest that inner city AA
      children and their parents often do not recognize being overweight or the health
      implications of being overweight.

PMID- 18089232
TI  - Relationships between dissatisfaction with specific body characteristics and the
      Sociocultural Attitudes Toward Appearance Questionnaire-3 and Objectified Body
      Consciousness Scale.
AB  - Body dissatisfaction was studied in 123 predominately European-American college
      women. Desired changes in body characteristics were associated with scores on the
      Sociocultural Attitudes Toward Appearance Questionnaire (SATAQ-3) and the
      Objectified Body Consciousness Scale (OBCS). All SATAQ-3 measures were associated
      with desired changes in bust size and height, but were not related to desired
      upper body size. In contrast, the OBCS Surveillance and Body Shame Scales were
      related to desired upper body size, but were not related to desired bust size or
      height. As hypothesized, the SATAQ-3 Pressure and Internalization-General Scales
      and the OBCS Surveillance and Body Shame Scales were related to desired weight
      and lower body size. Results indicate body dissatisfaction is a complex construct
      and different aspects of this construct are related to different dispositional
      measures. Results also indicate that the OBCS is a more narrowly focused measure
      than the SATAQ-3.

PMID- 18089233
TI  - Psychometric properties of the Situational Inventory of Body-Image Dysphoria
      Short form in a Spanish sample.
AB  - The primary objective of this study was to translate and validate Situational
      Inventory of Body-Image Dysphoria-Short form (SIBID-S) in a Spanish population.
      The scale consists of 20 items to assess the frequency of dysphoric body-image
      emotions in certain situational contexts, using a five-point rating scale. The
      questionnaire was administered to 214 women between the ages of 14 and 29 years,
      from primary and secondary schools and a university. Principal components
      analysis indicated a one-factor structure for the entire sample and both younger
      (<18) and older (>or=18) participants. Internal consistency was high (0.94), and
      the test-retest reliability over 1 month ranged between 0.89 and 0.93. The SIBID
      S showed good convergent validity in relation to other pertinent measures of body
      image, eating pathology, and self-esteem. Moreover, the SIBID-S was
      differentiated low-risk, subclinical eating disturbed, and clinical eating
      disordered patients. Results support the potential utility of the SIBID-S in the
      Spanish female population, including a younger group than previously studied, as
      well as its usefulness in the assessment of body image among females varying in
      degrees of eating pathology.

PMID- 18089234
TI  - Tattooing: An expression of uniqueness in the appearance domain.
AB  - The study aimed to explore the motivations underlying the practice of tattooing.
      There were 100 participants: 50 (30 men, 20 women) with tattoos, and a comparison
      group of 50 non-tattooed individuals. Participants completed measures of
      appearance investment, distinctive appearance investment, and need for
      uniqueness. It was found that tattooed individuals scored higher than the
      comparison group on need for uniqueness, but not on the appearance investment
      measures. Among the non-tattooed, need for uniqueness predicted future likelihood
      of getting a tattoo, and this relationship was mediated by distinctive appearance
      investment. These results support our conceptualization of tattooing as an
      expression of uniqueness in the appearance domain.

PMID- 18089235
TI  - The leg-to-body ratio as a human aesthetic criterion.
AB  - There are surprisingly few empirical studies on the aesthetic appeal of human
      legs, examining such variables as length or shape. The human legs are conspicuous
      in erotic contexts, but few studies have experimentally tested preferences for
      longer legs. This study examined the utility of the human leg-to-body ratio (LBR)
      as a specific aesthetic criterion among 71 British undergraduates. Participants
      rated for physical attractiveness line drawings that varied in five levels of
      LBR. The results showed that a longer LBR was preferred as maximally attractive
      in women, whereas a shorter LBR was preferred in men. Evolutionary psychological
      and socio-cultural explanations for this aesthetic preference are discussed, and
      the study's limitations are considered.

PMID- 18089236
TI  - Body-image thought processes: The development and initial validation of the
      Assessment of Body-Image Cognitive Distortions.
AB  - No measures exist that specifically assess cognitive distortions related to body
      image per se, despite their theoretical and clinical significance. Most cognitive
      distortion scales pertain to depression, anxiety, or eating disorders.
      Accordingly, the 37-item Assessment of Body-Image Cognitive Distortions (ABCD)
      was developed and validated in this study with a sample of 263 college women. The
      ABCD samples eight types of distorted thinking related to how persons process
      information about their physical appearance. Two 18-item parallel forms of the
      unidimensional measure were also constructed. All forms were highly internally
      consistent and relatively free from socially desirable responding. Convergent
      validity for all ABCD forms was established using several standardized measures
      of body image and eating attitudes. Multiple regression analysis showed that the
      ABCD was predictable from body-image evaluation, investment, and overweight
      preoccupation. The ABCD uniquely predicted body-image quality of life and
      disturbed eating attitudes above and beyond other body-image predictors. Heavier
      women and White women were more prone to body-image cognitive distortions than
      were thinner women and Black women. Finally, limitations of this preliminary
      study, directions for future research, and clinical implications are discussed.

PMID- 18089237
TI  - Development and validation of the verbal commentary on physical appearance scale:
      Considering both positive and negative commentary.
AB  - Two studies describe the development and validation of the Verbal Commentary on
      Physical Appearance Scale (VCOPAS). In Study 1, 320 undergraduate female students
      completed the scale and factor analyses were conducted. Study 2 included 246
      undergraduate female students and a confirmatory factor analysis (CFA) replicated
      the initial factor structure. The final VCOPAS consists of 21 items and contains
      three subscales (Negative Weight and Shape, Positive Weight and Shape, and
      Positive General Appearance). The total scale and subscales demonstrated good
      internal consistency and test-retest reliability (all >.70). Significant
      correlations were found between VCOPAS subscales and measures of physical
      appearance-related feedback, body image disturbance, and self-esteem. Regression
      analyses indicated the utility of the Negative Weight and Shape, Positive Weight
      and Shape, and Positive General Appearance subscales in explaining significant
      variance associated with body image disturbance and self-esteem. The VCOPAS is
      likely to be useful in future research examining the role of appearance-related
      commentary in the development and maintenance of body image dissatisfaction and
      eating disturbance.

PMID- 18089238
TI  - The effects of a physical activity and nutrition intervention on body
      dissatisfaction, drive for thinness, and weight concerns in pre-adolescents.
AB  - The primary aim was to examine the effects of a physical activity and nutrition
      intervention on Body Dissatisfaction, Drive for Thinness, and Weight Concerns in
      pre-adolescents. Eighty-four 10-12 years old were studied as part of a larger
      trial of a family-based physical activity and nutrition intervention. Forty-nine
      children participated in the 8-week intervention (35 in control group) and
      completed Body Dissatisfaction, Drive for Thinness, and Weight Concerns measures
      at baseline and post-test. Participants in both groups showed positive but non
      significant changes in body image and Drive for Thinness following the trial, but
      there were no significant between group differences. This was the first study to
      examine the effects of a physical activity and nutrition intervention on body
      image and related variables in pre-adolescents. Body Dissatisfaction, Drive for
      Thinness, and Weight Concerns were not positively or negatively influenced by the
      intervention.

PMID- 18089239
TI  - Messages about physical attractiveness in animated cartoons.
AB  - Relying upon a content analysis of one specific type of medium to which young
      people are exposed beginning at an early age, on a regular basis, and for many
      years (i.e., animated cartoons), the present study examines what types of
      messages are provided about being physically unattractive, physically attractive,
      and ordinary-looking. This research concerns itself with identifying the
      characteristics that tend to be associated with being good-looking or
      unattractive, and then discussing the implications of the findings. Results
      indicate that many variables were found to differ based on cartoon characters'
      physical attractiveness, including gender, age, intelligence, body weight,
      emotional states experienced, prosocial behaviors, antisocial behaviors, and
      overall goodness/badness. Whenever differences were found, the overriding
      tendency was for cartoons to provide positive messages about being attractive and
      negative messages about being unattractive.

PMID- 18089240
TI  - The differential depiction of female athletes in judged and non-judged sport
      magazines.
AB  - Sports magazines portrayal of female athletes over the past ten years, in terms
      of body size, age, and race was examined. Using the Contour Drawing Rating Scale
      (CDRS), estimated body size was obtained for cover models on a set of judged and
      non-judged sport magazines. The frequency with which the full bodies of models
      were depicted on the covers of these magazines was also investigated. Cover
      models on judged sport magazines were rated as significantly thinner than cover
      models on non-judged sport magazines. Judged sport magazines also displayed a
      higher number of full-body images than non-judged sport magazines. These findings
      suggest that individuals who read judged sport magazines are more likely to be
      exposed to thin media images than those reading non-judged sport magazines.

PMID- 18089241
TI  - The interference effect of men's handling of muscular action figures on a lexical
      decision task.
AB  - It has been shown in previous work [Action figures and men. Sex Roles 53, 877
      885] that male participants who handled extremely muscular action figures had
      lower body esteem than those who did not handle action figures or a Ken doll.
      However, the internal mechanisms that dictated this effect are unclear.
      Therefore, the current study extended this previous work by having male
      participants handle action figures of varying muscularity and completing a
      lexical decision task with target words that consisted of both positive and
      negative body words and feeling words in order to determine if males would be
      primed to think negatively about their bodies and self or if positive thoughts
      about their bodies and self would be interfered with. The results show that those
      participants who handled the extremely muscular action figures responded
      significantly more slowly to feeling positive words (e.g., content, confident)
      and marginally more slowly to body positive words (e.g., muscle, bicep) than
      those who did not handle any action figures. Overall, this suggests that the
      interference of positive words, not the priming of negative words, is the
      internal mechanism that produces the decreased body image satisfaction after
      exposure to muscular stimuli. Implications and future research are discussed.

PMID- 18089242
TI  - Applicability of the Somatomorphic Matrix computer program in Japanese and
      Australian Caucasian males in relation to measured body composition.
AB  - The Somatomorphic Matrix (SM) is a computer-based body image assessment program
      that allows assessment of the individual's body image in relation to known body
      composition values. To date, no study has compared the SM results to the measured
      body composition and assessed the usefulness in multi-ethnic samples. Japanese
      and Australian Caucasian males underwent testing to examine the SM body image
      results to their measured body composition. Japanese males showed significant
      (p<0.01) discrepancy in their measured and the perceived 'current' muscularity
      compared with Australians. Both groups showed wide variability in the perception
      of their 'current' body composition in relation to the measured values,
      indicating an incomparability of the SM results to the measured results. The
      study also showed Japanese males to have lower consistency in the SM results than
      Australian males after a 12-month interval. In order to use the program in multi
      ethnic populations further development of the program is recommended.

PMID- 18089243
TI  - Body size preferences and sociocultural influences on attitudes towards obesity
      among Moroccan Sahraoui women.
AB  - The purpose of this investigation was to study body size preferences and to
      examine the influence of sociocultural factors on obesity among 249 Moroccan
      Sahraoui women. Participants rated their ideal body size and the size they
      thought to be "healthy," using a figural scale consisting of nine images ranging
      from thin to obese. They also noted which particular sociocultural influences
      affected their body size ratings. The results indicated that women's rating of
      ideal body size (4.88) was significantly larger than their rating of healthy body
      size (4.33). The desire to lose weight was very low even among the majority of
      obese women, and educational level did not affect desire to lose weight. Women
      not satisfied with their body size were more likely to report trying to gain
      weight rather than to lose it. The major factors reported to influence body size
      ideal were mothers, men, and traditional clothing. It is an enormous challenge
      for the health institutions of Morocco to prevent obesity and its complications.
      Prevention programs should include teenagers and key family members.

PMID- 18089244
TI  - The Negative Physical Self Scale: Initial development and validation in samples
      of Chinese adolescents and young adults.
AB  - This research presents four studies on the initial development and validation of
      the 48-item Negative Physical Self Scale (NPS), a multidimensional measure of
      body image concerns for use with Chinese samples. In Study 1 (N=1095),
      exploratory factor analyses identified five dimensions underlying the NPS
      (General Appearance, Facial Appearance, Shortness, Fatness, Thinness). In Study 2
      (N=1057), confirmatory factor analyses replicated this factor structure. In
      Studies 3 and 4, the validity of all NPS dimensions except Thinness Concern was
      supported via their patterns of relation with both objective physical
      characteristics/behaviors and other self-report measures of body image and
      general self worth. Because Chinese adolescents and young adults expressed
      relatively more concerns about General Appearance, Shortness, and Facial
      Appearance than about Fatness, the NPS may have greater utility for assessing
      body image disturbances in China than existing measures that focus exclusively on
      general body satisfaction and body size/weight.

PMID- 18089245
TI  - The swimsuit issue: Correlates of body image in a sample of 52,677 heterosexual
      adults.
AB  - Past research on adults' body image has typically used small convenience samples,
      limiting the ability to examine associations of personal characteristics to body
      satisfaction. This study of 52,677 heterosexual adults ages 18-65 examined
      associations of body satisfaction to age, height, gender, and body mass index
      (BMI). Age and height were mostly unrelated to body satisfaction. Consistent with
      an Objectification Theory perspective, fewer men than women reported being too
      heavy (41% versus 61%), rated their body as unattractive (11% versus 21%), or
      avoided wearing a swimsuit in public (16% versus 31%). Men felt better about
      their bodies than women across most of the weight span, although among
      underweight individuals, women felt better than men. Slender women (BMIs 14.5
      22.49) were more satisfied than most other women (BMIs 22.5-40.5). Among men,
      underweight and obese men were least satisfied. These findings highlight gender
      differences in the association of weight to body satisfaction.

PMID- 18089246
TI  - Validation of the Sociocultural Attitudes Towards Appearance Questionnaire-3
      among a random sample of Jordanian women.
AB  - Measuring the impact of westernization on body image is an important element in
      understanding body dissatisfaction and eating disorders in countries undergoing
      cultural transitions. The purpose of this study was to evaluate the validity and
      reliability of the Sociocultural Attitudes Towards Appearance Questionnaire-3, a
      measure of societal and media impacts on body image, in a non-western population.
      Factor analyses identified the same four subscales found in the original
      validation with high Cronbach's alpha coefficients and Guttman split-half
      coefficients, and low item cross-loadings. Furthermore, mean score comparisons by
      demographic variables on each subscale indicated that subscale scores were only
      affected by age. The results suggest that the Sociocultural Attitudes Towards
      Appearance Questionnaire-3 is a valid and reliable instrument for Jordanian
      women. The high level of validity and reliability for this population lends
      support for the possible use of this scale in other non-western populations after
      appropriate pretesting.

PMID- 18089247
TI  - Day-to-day body-image states: prospective predictors of intra-individual level
      and variability.
AB  - Most body-image research has focused on the trait level of body-image evaluation,
      often neglecting the momentary fluctuations many people experience in everyday
      life. The present prospective study investigated whether theory-relevant body
      image measures, perfectionistic self-presentation, and eating attitudes would
      predict average day-to-day body-image levels and their intra-individual
      variability. A convenience sample consisted of 121 women from two universities.
      In Phase 1 of the study, participants completed an online battery of selected
      body-image and personality questionnaires. In Phase 2, participants went online
      to complete the dependent measure, the Body Image States Scale, once per evening
      over 10 days. As hypothesized, more favorable body-image state levels were
      associated with less investment in appearance for self-worth, less body-image
      disturbance, fewer body-image cognitive distortions, less disturbed eating
      attitudes, and lower body mass. Moreover, greater day-to-day body-image
      variability was predicted by greater psychological investment in appearance, more
      body-image cognitive distortions, and higher perfectionistic self-presentation.
      Implications and future directions for research are discussed.

PMID- 18089248
TI  - Ten-year-old girls' and boys' body composition and peer victimization
      experiences: prospective associations with body satisfaction.
AB  - This study examined prospective associations between 10-year-olds' weight and
      height, their perception of shape and stature, frequent experiences of peer
      victimization, and different aspects of body esteem at age 13. Participants were
      474 girls and 400 boys participating in a two-wave longitudinal questionnaire
      study. Main results were that whereas actually being heavier built at age 10 was
      associated with girls' increments in body dissatisfaction, the mere perception of
      being too heavy was associated with boys' poorer body satisfaction. Also, boys
      who believed that they were too short were more dissatisfied at follow-up.
      Whereas frequent peer victimization had long-term associations with girls' weight
      esteem, teasing targeted towards appearance was associated with boys' more
      negative beliefs about what others think about their appearance. Finally,
      participants had become significantly more dissatisfied at age 13, suggesting
      that this is a time in life when both girls and boys risk becoming increasingly
      critical towards their appearance.

PMID- 18089249
TI  - Self-schema and social comparison explanations of body dissatisfaction: a
      laboratory investigation.
AB  - The current study was an investigation of the self-schema and social comparison
      theories of body dissatisfaction. The social comparison manipulation consisted of
      exposure to one of three levels of comparison figure: upward, downward, or no
      comparison. Two different imagery exercises served to prime either a
      participants' appearance self-schema, or a non-appearance schema. Participants
      completed state measures of body image and mood at pre- and posttest. Results
      indicated no significant interaction between priming and social comparison and no
      significant main effect for priming. However, there was a significant effect of
      social comparison, such that those in the downward comparison condition showed an
      increase in body satisfaction and positive mood. Results are discussed in the
      context of self-schema theory and social comparison, and suggestions are given
      for future research that might further shed light on these theoretical approaches
      for understanding body dissatisfaction.

PMID- 18089250
TI  - Self-esteem threat combined with exposure to thin media images leads to body
      image compensatory self-enhancement.
AB  - This study examined the effect of a self-esteem threat combined with exposure to
      thin images on body image (BI) satisfaction and investment. Female participants
      (N=94) received a self-esteem threat consisting of false failure feedback or
      received false success feedback on an intellectual task allegedly highly
      predictive of academic and professional success. They then viewed media images
      featuring thin models or products. After viewing thin models, women who had
      received failure feedback declared themselves more satisfied about their
      appearance and less invested in it than did women who had received success
      feedback. These results suggest that exposure to the thin ideal may inspire women
      experiencing self-esteem threats to use appearance as an alternative source of
      worth, thus maintaining their global esteem through BI compensatory self
      enhancement. Potential long-term implications of this strategy, such as a
      paradoxical increase in BI investment and the development of eating pathology,
      are discussed.

PMID- 18089251
TI  - Body images of patients with anorexia nervosa, bulimia nervosa and female control
      subjects: a comparison with male ideals of female attractiveness.
AB  - Body images of female patients with anorexia nervosa and bulimia nervosa were
      assessed against females without eating disorders and compared with male ideals
      of female attractiveness. A computer program was applied to examine body images
      of 62 patients with anorexia nervosa, 45 patients with bulimia nervosa, and 40
      female and 39 male control subjects. Body size overestimation was most distinct
      in the two patient groups. Self-ideal discrepancy was highest in bulimia nervosa.
      Estimation of the society's ideal female body in all three female groups did not
      differ from men's perception of the most attractive female body. Congruence of
      ideals of female attractiveness in patients, female, and male control subjects
      and described differences between patients and female controls support the theory
      that body image disturbance is a problem of processing self-referential
      information regarding body image rather than a problem of processing body image
      related information per se.

PMID- 18089252
TI  - Perceptions and metaperceptions of same-sex social interactions in college women
      with disordered eating patterns.
AB  - This study compared perceptions and metaperceptions after a social interaction
      between a woman with disordered eating (subclinical bulimia nervosa) and a female
      interaction partner. Hypotheses were: women with disordered eating would have
      more negative metaperceptions of social interactions than women without
      disordered eating, and women with disordered eating would show a greater
      discrepancy between metaperceptions and perceptions than women without disordered
      eating. All participants completed questionnaires about their perceptions and
      metaperceptions post-interaction. Results showed women with disordered eating
      thought that they had made a negative impression; findings addressing the
      relationships among social desirability, loneliness, social support utilization,
      and fear of negative evaluation are also discussed.

PMID- 18089253
TI  - Investigation of ethnic differences in body image between Hispanic/biethnic
      Hispanic and non-Hispanic White preadolescent girls.
AB  - The extent to which the construct of body image is measurement invariant across
      ethnic groups is an important consideration for studies examining ethnic
      differences and characteristics that influence body image disturbances. However,
      the literature examining the body image construct as a function of ethnic group
      membership is limited. The primary aim of this study was to investigate whether
      Hispanic/biethnic-Hispanic and non-Hispanic White preadolescent girls (aged 8
      through 12 years old; N=141) had fundamentally different conceptualizations of
      body image in a low to low/middle socioeconomic status school-based sample. Our
      findings suggest that the measurement construct of body image was similar and
      relatively stable for Hispanic/biethnic-Hispanic and non-Hispanic White
      preadolescent girls. In addition, the body image construct was predictably
      related to disordered eating symptoms in both groups, with different dimensions
      of body image differentially predictive by ethnic group. Overall, body image
      appears to be a meaningful construct with similar measurement meanings across
      Hispanic/biethnic-Hispanic and non-Hispanic White ethnic groups.

PMID- 18089254
TI  - Assessing body image in patients with systemic sclerosis (scleroderma):
      validation of the adapted Satisfaction with Appearance Scale.
AB  - People with scleroderma often experience disfiguring appearance-related changes
      in socially visible and interpersonally salient areas. Although disfigurement can
      lead to body image dissatisfaction, this phenomenon has not been well
      investigated due to the lack of a disfigurement-specific measure. The
      Satisfaction With Appearance (SWAP) scale, previously developed in burn
      survivors, was adapted and administered to 254 participants with scleroderma to
      evaluate its psychometric integrity and its validity for use in a different
      medical population that experiences changes in appearance. Principal component
      analysis revealed two factors - Subjective Dissatisfaction and Perceived Social
      Impact - rather than the four found in burn victims. Excellent estimates of
      internal consistency and temporal stability and strong evidence for the
      reliability of the two-factor solution were found. The resulting factor structure
      in a scleroderma population suggests that differing medical conditions may create
      alternate constellations of BID, reflects the need for body image researchers to
      assess psychometrics across medical populations and may have clinical
      implications for BID interventions.

PMID- 18089255
TI  - Modifying the body: motivations for getting tattooed and pierced.
AB  - Body modifications have been prevalent for centuries and are practiced for a
      great variety of reasons. Lately, tattoos and body piercings have become
      increasingly popular. Thus, a profound understanding of the underlying
      motivations behind obtaining tattoos and body piercings nowadays is required. A
      considerable body of research on motivational aspects already exists, mainly
      using explorative approaches to describe motivations. In this paper we provide a
      review of the existing relevant literature. Furthermore, we establish ten broad
      motivational categories, comprising motivations for getting tattooed and body
      pierced, for reference in future research.

PMID- 18089256
TI  - Evaluating self and partner physical attractiveness.
AB  - This study used a novel questionnaire to examine ratings of self and partner
      physical attractiveness. Seventy-two men and 83 women estimated their own and
      their opposite-sex partner's overall physical attractiveness and the
      attractiveness of various body parts and measures. They also answered six simple
      questions concerning physical attractiveness. Results showed significant gender
      differences in self-estimates of overall facial attractiveness and upper body
      features. In general, and regardless of gender, participants rated their opposite
      sex partners as being significantly more attractive than themselves. In addition,
      the results showed that body weight and facial attractiveness were the best
      predictors of overall physical attractiveness. Implications of these results in
      terms of social biases are considered.

PMID- 18089257
TI  - Gender and ethnic differences in body image and opposite sex figure preferences
      of rural adolescents.
AB  - This study examined whether rural adolescents would report gender and ethnic
      differences in body image similar to those that have been observed in urban
      samples. Data were analyzed for 384 rural adolescents (57% African American, 43%
      Caucasian, mean age 13 years) to determine gender and ethnic differences in body
      dissatisfaction, body size discrepancy, and current and ideal figure ratings.
      Females wanted to be smaller and reported more body dissatisfaction than did
      males. Caucasian females reported the most body dissatisfaction. African
      Americans reported larger current and ideal figure ratings than did Caucasians.
      African Americans preferred larger opposite sex figures than did Caucasians. Both
      African American and Caucasian males selected a larger female figure as ideal
      than was selected by females. Results demonstrated that gender and ethnic
      differences exist in body image for rural adolescents. This frequently overlooked
      population may benefit from further study. Implications of findings and
      limitations of the study are also discussed.

PMID- 18089258
TI  - Healthy Schools-Healthy Kids: a controlled evaluation of a comprehensive
      universal eating disorder prevention program.
AB  - This study was a controlled evaluation of a comprehensive school-based universal
      prevention program involving male and female students, parents, teachers, school
      administrators and local public health professionals. A total of 982 male and
      female Grades 6 and 7 middle school students (and 91 teachers/school
      administrators) completed self-report surveys at baseline on measures of body
      satisfaction, internalization of media ideals, size acceptance, disordered
      eating, weight-based teasing, weight loss and muscle-gaining behaviours, and
      perceptions of school climate (teachers only). Eighty-four percent of the
      students repeated the surveys immediately following the 8-month school-wide
      intervention and 71% again 6 months later. Repeated measures ANCOVAs revealed
      that participation in the Healthy Schools-Healthy Kids (HS-HK) program had a
      positive influence by reducing the internalization of media ideals among male and
      female students and by reducing disordered eating among female students. The
      program was also associated with reductions in weight-loss behaviours among the
      students, although this effect was lost by the 6-month follow-up. When the
      intervention students were sub-divided into low versus high-risk groups, the high
      risk group appeared to benefit most from the intervention with significant
      reductions in internalization of media ideals, greater body satisfaction, and
      reduced disordered eating over time. There were no intervention effects for
      teachers. Challenges of engaging teachers in prevention are discussed.

PMID- 18089259
TI  - The impact of thin models in music videos on adolescent girls' body
      dissatisfaction.
AB  - Music videos are a particularly influential, new form of mass media for
      adolescents, which include the depiction of scantily clad female models whose
      bodies epitomise the ultra-thin sociocultural ideal for young women. The present
      study is the first exposure experiment that examines the impact of thin models in
      music videos on the body dissatisfaction of 16-19-year-old adolescent girls
      (n=87). First, participants completed measures of positive and negative affect,
      body image, and self-esteem. Under the guise of a memory experiment, they then
      either watched three music videos, listened to three songs (from the videos), or
      learned a list of words. Affect and body image were assessed afterwards. In
      contrast to the music listening and word-learning conditions, girls who watched
      the music videos reported significantly elevated scores on an adaptation of the
      Body Image States Scale after exposure, indicating increased body
      dissatisfaction. Self-esteem was not found to be a significant moderator of this
      relationship. Implications and future research are discussed.

PMID- 18089260
TI  - Childhood obesity stigma: association with television, videogame, and magazine
      exposure.
AB  - Although the stigmatization of obesity among children is highly prevalent, its
      origins and relationship to mass media exposure are largely unknown. Ninety boys
      and 171 girls aged 10-13 years (mean BMI=19.84) were asked to rank, in order of
      liking, 12 figures of peers depicted both with and without various disabilities
      or obesity, and to rate their attitudes towards the obese child on visual
      analogue scales. Weekly time spent watching television, watching videogames, and
      reading magazines on weekdays and weekends was assessed. Total media use,
      magazine use, and videogame use were significantly correlated with more negative
      reactions to obese girls and boys. Regression analyses revealed that greater
      dislike of obese children relative to their non-overweight peers was uniquely
      predicted by magazine reading time. Thus, media exposure was associated with
      stigmatizing attitudes towards obese children. Mass media sources may lead
      children to devalue and stigmatize peers with above-average body weights.

PMID- 18089261
TI  - Examining "fat talk" experimentally in a female dyad: how are women influenced by
      another woman's body presentation style?
AB  - Fat talk, the verbal dissatisfaction that women express about their bodies, was
      studied in a female dyad whereby participants interacted with a female
      confederate who either self-derogated, self-accepted, or self-aggrandized. A 2
      (participant body esteem: high vs. low) x3 (confederate style of body image
      presentation) design was used. Results revealed that participants' public
      disclosure of their body image varied according to confederate's style.
      Consistent with a reciprocity effect, participants disclosed the lowest public
      body image ratings in the self-derogate condition, with moderate ratings in the
      self-accept condition, and highest ratings in the self-aggrandize condition.
      Moreover, participants with low compared to high body esteem stated lower public
      body image. Participants' judgments of the confederates' likeability did not vary
      as a function of the confederate's body presentational style. Findings support
      the recursive nature of the social psychology of body image such that personal
      body image dissatisfaction is partially influenced by fat talk social norms.

PMID- 18089262
TI  - Understanding the relationship between obesity and positive and negative affect:
      the role of psychosocial mechanisms.
AB  - We examined the relationship between body mass index (BMI) and positive and
      negative affect, and evaluated whether this relationship is mediated (or
      suppressed) by physical health, intrusiveness of weight on physical functioning,
      and distressing interpersonal interactions. Analyses were based on a national
      sample of more than 3,000 adults ages 25 to 74. Class II (BMI 35-39.9) and Class
      III (BMI> or =40) obesity were associated with more frequent negative affect and
      less frequent positive affect, even after demographic and socioeconomic status
      characteristics were controlled. After the purported pathway variables were
      controlled, however, obese I persons reported significantly more frequent
      positive affect, while overweight, obese I, and obese II persons reported
      significantly less frequent negative affect, compared to normal weight persons.
      These patterns did not differ significantly by race or gender. Our findings
      suggest that excessive body weight is not necessarily distressing, yet the
      physical and interpersonal strains associated with obesity may impair one's mood.
      We discuss the implications for policy and practice.

PMID- 18089263
TI  - Ethnic differences in BMI, weight concerns, and eating behaviors: comparison of
      Native American, White, and Hispanic adolescents.
AB  - Evidence suggests that substantial proportions of adolescents, regardless of
      ethnicity or gender, are engaged in excessive weight control behaviors. Crago and
      Shisslak (2003), however, have noted that small samples and poorly validated
      instruments have limited the value of previous ethnic difference studies. Using
      the McKnight Risk Factor Survey, we compared Native American, White, and Hispanic
      adolescents. Native students were divided into groups with one (NA-mixed) or two
      (NA) Native American biological parents. Surveys were completed by 5th through
      10th grade students. BMI z-scores were significantly higher for boys and girls in
      the NA group, and boys in this group were significantly more engaged in weight
      control behaviors, including purging. A higher percentage of Native and Hispanic
      girls preferred a larger body size. BMI was positively correlated with weight and
      shape concerns and with weight control behaviors, regardless of ethnicity or
      gender. Overweight among Native adolescents may put them at greater risk for
      eating problems than their White peers.

PMID- 18089264
TI  - Dieting behaviors, body shape perceptions, and body satisfaction: cross-cultural
      differences in Argentinean and Swedish 13-year-olds.
AB  - This exploratory study represents a cross-cultural effort to examine differences
      in dieting practices and weight loss attempts, perceived body shape, and body
      satisfaction between young Argentinean and Swedish adolescents. The study group
      consisted of 358 Argentinean (193 girls, 165 boys) and 874 Swedish (474 girls,
      400 boys) 13-year-olds. A main finding was that Argentinean and Swedish
      adolescents did not differ on body satisfaction, although girls in both countries
      displayed greater body dissatisfaction than did boys. Dieting and weight loss
      attempts were more prevalent among the Argentinean adolescents, especially among
      girls, and did not appear to depend on overweight or perception of body shape.
      The samples also differed in their perceptions of body shape and the effect those
      perceptions had on their body satisfaction, with Swedish adolescents suffering
      more from negative body shape perceptions.

PMID- 18089266
TI  - Body image and suicidal ideation in adolescents.
AB  - Data from 231 adolescents (mean age=15.7, SD=1.39) were collected from a public
      school setting in the United States. Participants completed several measures,
      including those assessing depression, hopelessness, past suicidal behavior, body
      image, and current suicidal ideation. It was hypothesized that depression,
      hopelessness, past suicidal behavior, and body image (a risk factor seldom
      examined) would significantly predict current suicidal ideation and that there
      would be gender differences for body image. Regression analyses indicated that
      all risk factors including body image were significant predictors of current
      suicidal ideation for the whole sample. For both males and females, body image
      offered a unique contribution to the measurement of suicide ideation above and
      beyond the other risk factors, with body attitudes/feelings being the strongest
      predictor. Results encourage the inclusion of body image as a variable in risk
      models for adolescent suicidal ideation, as it likely accounts for additional
      variance above and beyond traditional risk factors.

PMID- 18089265
TI  - The association between body image and smoking cessation among individuals living
      with HIV/AIDS.
AB  - Lower smoking cessation rates are associated with body image concerns in the
      general population. This relationship is particularly important to study in
      individuals living with HIV/AIDS due to alarmingly high smoking rates and
      considerable bodily changes experienced with HIV disease progression and
      treatment. The association between body image and smoking cessation rates was
      examined among individuals living with HIV/AIDS participating in a smoking
      cessation intervention. Body image concerns were significantly associated with
      depression, anxiety, stress, and social support, all variables known to affect
      cessation rates. However, reduced quit rates were found among individuals
      reporting elevated and low levels of body image concerns at the end of treatment.
      These findings suggest a unique relationship between smoking and body image among
      individuals living with HIV/AIDS. Further research is needed to examine these
      effects and whether moderate levels of body image concerns in this population
      reflect realistic body perceptions associated with positive mental health.

PMID- 18089267
TI  - Personality information: does it influence attractiveness ratings of various body
      sizes?
AB  - In the present study, the influence of personality information on attractiveness
      ratings of different body sizes was examined. Specifically, participants were
      presented with either no personality information, negative information, or
      positive information about a hypothetical female target and asked to rate the
      smallest and largest figure that they would consider attractive for her using a
      figure rating scale. Consistent with the study hypotheses: (1) participants chose
      a wider range of figures as attractive for a female described to have a positive
      personality when compared to the range chosen when no personality information was
      provided; (2) females selected wider attractive ranges than males; and (3) other
      participant characteristics (i.e., physical appearance anxiety and body mass)
      were found to predict attractive ranges selected by participants. These findings
      may have implications for the treatment of body-image disturbance, as the
      findings suggest that personality, rather than appearance alone, may be a factor
      in perceptions of attractiveness of various body sizes.

PMID- 18089268
TI  - Preferences for female body size in Britain and the South Pacific.
AB  - To assess current attitudes to body weight and shape in the South Pacific, a
      region characterised by relatively high levels of obesity and traditionally
      positive views of large bodies, 38 high socio-economic status (SES) adolescent
      males and 38 low SES adolescent males in Independent Samoa were asked to rate a
      set of images of real women for physical attractiveness. Participants in both SES
      settings preferred women with a slender figure, as did a comparison group in
      Britain, suggesting that the traditional veneration of large bodies is no longer
      apparent in Samoa. However, the results also showed that low SES adolescents were
      more likely to view overweight figures as attractive, which suggests that the
      veneration of slim figures may be associated with increasing SES. Implications of
      this finding are discussed in conclusion.

PMID- 18089269
TI  - Evaluating the effectiveness of psychosocial interventions for individuals with
      visible differences: a systematic review of the empirical literature.
AB  - The objective of this review was to systematically identify and evaluate all
      known studies testing empirically the efficacy of psychosocial intervention
      programmes for adults with visible differences. Twelve papers met the inclusion
      criteria. None of the papers demonstrated adequately the clinical effectiveness
      of the interventions. The review concluded that further research was needed to
      demonstrate adequately the effectiveness of existing interventions, and a greater
      number of Randomised Controlled Trials and experimental studies were required to
      increase the methodological validity of intervention studies.

PMID- 18089270
TI  - Does severity predict distress? The relationship between subjective and objective
      measures of appearance and psychological adjustment, during treatment for facial
      lipoatrophy.
AB  - The intuitive or lay belief that the severity of a disfiguring condition predicts
      psychological distress is not demonstrated in clinical practice, nor in research
      studies. This within group study used standardised measures repeated at six month
      intervals, to investigate the relationship between subjective and objective
      measures of appearance and psychological adjustment in 51 patients undergoing
      treatment for facial lipoatrophy using a synthetic filler, Newfill. Results
      demonstrate a dissociation between objective and subjective measures with only
      subjective assessment predicting psychological outcomes. It is recommended that
      Moss's (2005) hypothesis of discrete group membership (normal/not normal) should
      be adapted to include an internal standard for comparison, and that all
      evaluations of treatment modifying disfigurement should include a standardised
      subjective measure of appearance.

PMID- 18089271
TI  - Body image and explicit and implicit anti-fat attitudes: the mediating role of
      physical appearance comparisons.
AB  - Prejudice against overweight people is rife. However, there is a paucity of
      research on the underlying reasons for it. In two studies the relationship
      between body image, the tendency to make physical appearance-related comparisons
      (PACS), and both explicit and implicit anti-fat attitudes was examined. In Study
      1 (n = 227) people with a high tendency to make physical appearance-related
      comparisons (high PACS scorers) reported lower self-appearance evaluation, but
      higher appearance orientation and explicit anti-fat attitudes. The PACS fully
      mediated the relationship between appearance orientation and explicit anti-fat
      attitudes. Study 2 (n = 134) found that the PACS also mediated the relationship
      between appearance orientation and implicit anti-fat attitudes. Thus, individual
      differences in factors such as body image and the tendency to make appearance
      related comparisons, appear to play a central role in both explicit and implicit
      anti-fat attitudes.

PMID- 18089272
TI  - Body dissatisfaction and body comparison with media images in males and females.
AB  - This study examined the role of media body comparison as a mediator of the
      relationships between psychological factors and sociocultural pressures to be
      thin and body dissatisfaction in both females and males. Participants were 1,386
      females (mean age = 19.37 years) and 1,130 males (mean age = 19.46) from diverse
      backgrounds who completed a self-report questionnaire. Path analysis was used to
      test a cross-sectional model in which media body comparison mediated the impact
      of self-esteem, depressive mood, parent dieting environment, friend dieting, TV
      exposure, magazine message exposure, weight teasing and body mass index (BMI) on
      body dissatisfaction. In females, media body comparison partially or fully
      mediated relationships between self-esteem, depressive mood, friend dieting,
      magazine message exposure and BMI, and body dissatisfaction. In males, media body
      comparison was not a significant predictor of body dissatisfaction. This research
      particularly highlights the need to further examine processes that are involved
      in the development of body dissatisfaction in males.

PMID- 18089273
TI  - Gaming magazines and the drive for muscularity in preadolescent boys: a
      longitudinal examination.
AB  - The development of a drive for muscularity among boys has been linked to various
      cultural influences, one of which is exposure to mass media depicting the
      muscular male body ideal. We sought to determine whether self-reported exposure
      to four ideal-body magazine genres (health/fitness, fashion, sports, and gaming)
      predicted an increased drive for muscularity 1 year later. A sample of 104 Black
      and 77 White preadolescent boys (mean age 8.77) participated in a 2-wave
      longitudinal panel study. Controlling Wave 1 grade, perceived thinness/adiposity,
      and drive for muscularity, exposure to video gaming magazines predicted a
      significant increase in Wave 2 drive for muscularity, but only for White boys.
      Discussion calls for the inclusion of video gaming magazine exposure measures in
      future research on print media and male body ideals, along with empirical
      exploration of racial themes in gaming magazines.

PMID- 18089274
TI  - The effects of exposure to muscular male models among men: exploring the
      moderating role of gym use and exercise motivation.
AB  - This study examines the effects of exposure to the muscular male body ideal on
      body-focused negative affect among male gym users and non-exercisers. As
      hypothesized, the impact of media exposure depended on men's exercise status. Non
      exercisers (n = 58) reported greater body-focused negative affect after exposure
      to images of muscular male models than after neutral images (no model controls),
      whereas gym users (n = 58) showed a tendency for less body-focused negative
      affect after the model images than after the control images. Furthermore, the
      extent to which gym users were motivated to increase strength and muscularity
      moderated these exposure effects; men who reported stronger strength and
      muscularity exercise motivation reported a greater degree of self-enhancement
      after exposure to the muscular ideal. The findings are interpreted with respect
      to likely differences in motives for social comparisons.

PMID- 18089275
TI  - Support for the uniqueness of body dissatisfaction from drive for muscularity
      among men.
AB  - This study explored whether three dimensions of men's body dissatisfaction
      (muscularity, body fat, and height) are distinct from drive for muscularity (body
      image, behaviors, and attitudes) in a sample of 368 college men. If body
      dissatisfaction is a unique construct, then it will be associated with
      psychological well-being above and beyond the variance accounted for by drive for
      muscularity body image, behaviors, and attitudes. Findings revealed such
      incremental evidence, supporting body dissatisfaction's unique contribution to
      all five investigated indices of psychological well-being. Overall, body
      dissatisfaction and drive for muscularity are not completely parallel constructs,
      highlighting the need to assess men's dissatisfaction with their muscularity,
      body fat, and height for a more comprehensive picture of their body image.

PMID- 18089276
TI  - Sociocultural pressures, thin-ideal internalization, self-objectification, and
      body dissatisfaction: could feminist beliefs be a moderating factor?
AB  - Theory and research suggest that sociocultural pressures, thin-ideal
      internalization, and self-objectification are associated with body
      dissatisfaction, while feminist beliefs may serve a protective function. This
      research examined thin-ideal internalization and self-objectification as
      mediators and feminist beliefs as a moderator in the relationship between
      sociocultural pressures to meet the thin-ideal and body dissatisfaction. Female
      undergraduate volunteers (N=195) completed self-report measures assessing
      sociocultural influences, feminist beliefs, thin-ideal internalization, self
      objectification, and body dissatisfaction. Multisample structural equation
      modeling showed that feminist beliefs moderate the relationship between media
      awareness and thin-ideal internalization, but not the relationship between social
      influence and thin-ideal internalization. Research and clinical implications of
      these findings are discussed.

PMID- 18089277
TI  - Experimental effects of receiving negative weight-related feedback: a weight
      guessing study.
AB  - The effects of receiving negative verbal weight-related feedback on the mood,
      self-esteem, and body image of restrained and unrestrained eaters were
      investigated. Female undergraduate students either reported their current weight
      (no feedback) or had their weight guessed as 15 lb higher than their actual
      weight (negative feedback) by an experimenter who presented herself as either an
      undergraduate (peer) or graduate student (non-peer). Participants overall had
      higher anxiety and felt "fatter" in the negative feedback condition. When this
      feedback came from a peer they felt fatter, more dissatisfied with their bodies,
      and, for restrained eaters, more depressed, as compared to when it came from a
      non-peer. These results provide empirical evidence that negative weight-related
      feedback produces adverse psychological consequences for young women, especially
      restrained eaters, and suggest the importance of peers' perceptions of weight.

PMID- 18089278
TI  - Prevention program for disturbed eating and body dissatisfaction in a Spanish
      university population: a pilot study.
AB  - A pilot study was carried out in university students to evaluate the effect of a
      health promotion program for eating disturbances and body dissatisfaction. A
      subgroup of 135 medical students of both sexes in their second year was selected.
      There were divided in three groups, high-risk students (EDI >40) and low-risk
      students (EDI <40) who participated in the program and nonparticipants as
      comparison group. Program had a total of 16 workshops of 90 min. A year later the
      different assessment measurements were compared, body image, attitudes and eating
      behaviours, psychopathological levels and self-esteem. Differences by gender were
      found on the impact of the intervention. The program presented a statistical
      significant improvement in body-image satisfaction, eating attitudes only in high
      risk female students in the intervention group. This pilot program for eating
      disorder prevention in university populations can be considered effective, mainly
      in female populations at risk for developing an eating disorder.

PMID- 18089279
TI  - Don't take another bite: how sociocultural norms for appearance affect women's
      eating behavior.
AB  - Four studies tested the impact of exposure to thin images on women's eating
      behavior. In Study 1, women who were exposed to commercials containing thin
      models ate less in a taste test than women exposed to neutral commercials. The
      next two studies revealed that the impact of the thin images could be reduced by
      challenging the sociocultural norms for appearance. In Study 2, including images
      of relatively heavier women who have been successful in life (an indirect
      challenge to the norm) attenuated the impact of the thin images on women's eating
      behavior. Study 3 demonstrated that convincing women that their peers do not
      endorse the sociocultural norms also reduced the impact of the thin images. In
      Study 4, we found that exposure to thin images led to activation of an
      association between heaviness and rejection and that the more this association
      was activated, the less participants ate.

PMID- 18089280
TI  - Unattractive, promiscuous and heavy drinkers: perceptions of women with tattoos.
AB  - This study examined social and physical perceptions of blonde and brunette women
      with different degrees of tattooing. Eighty-four female and 76 male
      undergraduates rated a series of 16 female line drawings that varied in 2 levels
      of hair colour and 8 levels of tattooing. Ratings were made for physical
      attractiveness and sexual promiscuity, as well as estimates of the number of
      alcohol units consumed on a typical night out. Results showed that tattooed women
      were rated as less physically attractive, more sexually promiscuous and heavier
      drinkers than untattooed women, with more negative ratings with increasing number
      of tattoos. There were also weak interactions between body art and hair colour,
      with blonde women in general rated more negatively than brunettes. Results are
      discussed in terms of stereotypes about women who have tattoos and the effects of
      such stereotypes on well-being.

PMID- 18089281
TI  - Relationships amongst body dissatisfaction, internalisation of the media body
      ideal and perceived pressure from media in adolescent girls and boys.
AB  - Sociocultural factors that underpin gender differences in body dissatisfaction
      have not frequently been explored. We examined the relative contribution of
      internalization of media body ideals and perceived pressure to achieve this ideal
      in explaining body dissatisfaction in adolescent boys and girls. A sample of 819
      boys and 791 girls completed measures of internalization of body ideals,
      perceived pressure, body mass index (BMI) and body dissatisfaction. As expected,
      girls showed higher body dissatisfaction, internalization and pressure than boys.
      Internalization, pressure and BMI contributed to the prediction of body
      dissatisfaction in boys and in girls although these variables explained less
      variance in body dissatisfaction in boys. In addition, for girls the strongest
      predictor of body dissatisfaction was internalization, whilst for boys the
      strongest predictor was pressure. Differences in extent of internalization and
      pressure may contribute to higher body dissatisfaction in girls than boys. These
      sociocultural factors may affect girls and boys differently.

PMID- 18089282
TI  - The pursuit of muscularity among adolescent boys in Fiji and Tonga.
AB  - The desire for muscularity is tied to Western views of the male gender role,
      which prescribe that men be strong, physically fit and athletically successful.
      Although, these ideals have been primarily studied among Western adolescent boys,
      there is emerging evidence that the same ideals are valued and promoted among
      males from the Pacific Islands. The aim of the present study was to examine body
      image concerns associated with muscularity and the reasons for these concerns
      among Fijian and Tongan adolescent boys. Semi-structured interviews were
      conducted with 24 Indigenous Fijian, 24 Indo-Fijian, and 24 Tongan boys aged
      between 13 and 20 years. A thematic analysis of boys' narratives showed that the
      pursuit of muscularity was a dominant theme for many boys. Boys' reasons for
      pursing muscularity included the attainment of strength and fitness, sporting
      performance, physical work, dominance, and health. These findings are examined in
      relation to previous research with Western adolescent boys.

PMID- 18089283
TI  - A comparison of body perceptions in relation to measured body composition in
      young Japanese males and females.
AB  - The body composition of 139 Japanese females and 84 Japanese males (aged 18-30
      years) was measured using anthropometry to assess gender differences in body
      perceptions in relation to their measured values. Participants were asked to rate
      perceptions of their own "heaviness" and "fatness" and these were compared to
      their BMI and percent body fat (%BF). Japanese females showed a significantly
      greater desire to lose body weight (-4.20+/-0.6 kg) compared to males (0.27+/-1.4
      kg). Females also showed poor understanding of their "heaviness" and "fatness" in
      relation to actual body composition compared to males. The results confirmed
      distinct gender differences in body perception in relation to actual body
      composition and attitudes to weight management. Further promotion of "healthy"
      body image is recommended for the Japanese population.

PMID- 18089284
TI  - Perceived teasing experiences in body dysmorphic disorder.
AB  - Individuals with body dysmorphic disorder (BDD) are excessively concerned about
      imagined or slight defects in their appearance (e.g., asymmetrical facial
      features). Cognitive-behavioral models of BDD propose that several factors,
      including dysfunctional appearance-related beliefs and life experiences, such as
      teasing, contribute to the avoidance behaviors or rituals (e.g., mirror checking,
      grooming) characteristic of BDD. Previous research has demonstrated an
      association between perceived teasing and body dissatisfaction. In the current
      study, we examined whether individuals with BDD (n=16) report to have been teased
      more often than do mentally healthy controls (n=17). The group comprising
      individuals with BDD reported more appearance- and competency-related teasing
      than did control participants. This study provides preliminary evidence for the
      association between perceived teasing and BDD.

PMID- 18089285
TI  - Women's bust size and men's courtship solicitation.
AB  - Previous studies have found that women with larger breasts than the average were
      considered to be more physically attractive. In these studies attractiveness was
      measured with the help of silhouette figures or photographs and the effect of
      breast size on men's behaviour was not considered. In this study two experiments
      were carried out in order to test the effect of a woman's breast size on
      approaches made by males. We hypothesized that an increase in breast size would
      be associated with an increase in approaches by men. A young female confederate
      was instructed to wear a bra that permitted her to artificially vary her breast
      size. In the first experiment the female confederate was instructed to sit in a
      nightclub for one hour whereas in the second experiment she was instructed to
      take a seat in a pavement area of a bar. It was found that increasing the breast
      size of the female confederate was associated with an increasing number of
      approaches by men.

PMID- 18089286
TI  - The relative contribution of profile body shape and weight to judgements of
      women's physical attractiveness in Britain and Malaysia.
AB  - Ninety-six Malaysian and British men rated for physical attractiveness a set of
      photographs of real women in profile, with known body mass index (BMI) and waist
      to-hip ratio (WHR). Results showed that BMI accounted for the greater amount of
      variance in all settings. There were also significant differences in preferences
      for body weight, with low resource, low socioeconomic status (SES) raters
      preferring a significantly heavier partner than high resource, high SES raters.
      The disparity with previous findings using line drawings of women in profile was
      discussed in terms of the weaknesses of line-drawn stimuli.

PMID- 18089287
TI  - Subchronic treatment with fluoxetine attenuates effects of acute fluoxetine on
      female rat sexual behavior.
AB  - These experiments were designed to evaluate the hypothesis that fluoxetine
      induced sexual dysfunction in female rats derived from disruption of
      neuroendocrine events that normally facilitate sexual behavior. If so, exogenous
      hormonal priming to ovariectomized rats should eliminate fluoxetine's effect.
      Ovariectomized rats were subchronically treated with 10 mg/kg fluoxetine or
      distilled/deionized water vehicle for 9 consecutive days. On the 8th day of
      treatment, rats were primed with 10 microg estradiol benzoate followed 48 h later
      with 500 mug progesterone. In a pretest for sexual behavior on the 10th day,
      there was no difference between subchronic treatments. Sexual receptivity was
      again monitored 30 min after injection on the 10th day (acute treatment) with
      distilled/deionized water, 10 mg/kg fluoxetine or 20 mg/kg fluoxetine.
      Thereafter, the female's behavior was monitored for 20 min in a male preference
      procedure. After the acute treatment in rats subchronically treated with water,
      fluoxetine (10 or 20 mg/kg) significantly reduced both lordosis frequency and
      quality and reduced (but not significantly) time spent with the male. In rats
      subchronically treated with fluoxetine, the lordosis-inhibiting effect of an
      acute injection with fluoxetine was significantly attenuated relative to that of
      the subchronically water-treated rats. In contrast to expectation, subchronic
      treatment with fluoxetine increased, rather than reduced, the relative time
      females spent near the male. Activity, as measured by center crossings, and
      grooming were also reduced by subchronic treatment with fluoxetine.

PMID- 18089288
TI  - Fgf19 is required for zebrafish lens and retina development.
AB  - Fgf signaling plays crucial roles in morphogenesis. Fgf19 is required for
      zebrafish forebrain development. Here, we examined the roles of Fgf19 in the
      formation of the lens and retina in zebrafish. Knockdown of Fgf19 caused a size
      reduction of the lens and the retina, failure of closure of the choroids fissure,
      and a progressive expansion of the retinal tissue to the midline of the
      forebrain. Fgf19 expressed in the nasal retina and lens was involved in cell
      survival but not cell proliferation during embryonic lens and retina development.
      Fgf19 was essential for the differentiation of lens fiber cells in the lens but
      not for the neuronal differentiation and lamination in the retina. Loss of nasal
      fate in the retina caused by the knockdown of Fgf19, expansion of nasal fate in
      the retina caused by the overexpression of Fgf19 and eye transplantation
      indicated that Fgf19 in the retina was crucial for the nasal-temporal patterning
      of the retina that is critical for the guidance of retinal ganglion cell axons.
      Knockdown of Fgf19 also caused incorrect axon pathfinding. The present findings
      indicate that Fgf19 positively regulates the patterning and growth of the retina,
      and the differentiation and growth of the lens in zebrafish.

PMID- 18089289
TI  - Potential role of Nanos3 in maintaining the undifferentiated spermatogonia
      population.
AB  - Nanos gene encodes for zinc-finger protein with putative RNA-binding activity
      which shows an evolutionary conserved function in germ cell development. In the
      mouse, three Nanos homologs have been identified: Nanos1, Nanos2 and Nanos3. The
      Nanos3 ortholog is expressed in both male and female gonads of early embryo and,
      after birth, it is found only in the testis. Nanos3 targeted disruption results
      in the complete loss of germ cells in both sexes; however the role of Nanos3 in
      the testis during the postnatal period has not been explored yet. In this study,
      we show that, in prepuberal testis, Nanos3 is expressed in undifferentiated
      spermatogonia and that its up-regulation causes accumulation of cells in the G1
      phase, indicating that this protein is able to delay the cell cycle progression
      of spermatogonial cells. This is in line with the observation that the cell cycle
      length of the undifferentiated germ cells is longer than in differentiating
      spermatogonia. We also demonstrate a conserved mechanism of action of Nanos3,
      involving the interaction with the murine RNA-binding protein Pumilio2 and
      consisting of a potential translational repressor activity. According to the
      possible role of Nanos3 in inhibiting spermatogonia cell differentiation, we show
      that treatment with the differentiating factor all-trans retinoic acid induces a
      dramatic down-regulation of its expression. These results allow to conclude that,
      in the prepuberal testis, Nanos3 is important to maintain undifferentiated
      spermatogonia via the regulation of their cell cycle.

PMID- 18089290
TI  - Legalized pregnancy termination and septic abortion mortality in South Africa.

PMID- 18089291
TI  - Performance evaluation of cytometric bead assays for the measurement of lung
      cytokines in two rodent models.
AB  - There is a growing demand for a cost-effective, efficient, and high-throughput
      method for measuring cytokines. Currently, many studies are using flow cytometric
      bead-based multiplex assays in the measurement of cytokines. However, limited
      data are available regarding the performance of these cytometric bead assays
      versus enzyme-linked immunosorbent assay (ELISA) or correlation with mRNA
      expression using real time reverse transcriptase-polymerase chain reaction (RT
      PCR). In one of our studies, cytometric bead array (CBA) was used to measure
      inflammatory cytokine protein levels in bronchoalveolar lavage (BAL) samples from
      mice exposed to welding fume, an inflammatory particulate. The results were then
      compared to whole lung mRNA levels of the same cytokines measured by real time RT
      PCR in the same mouse model. It was found that the trends in cytokine profiles
      measured via CBA agreed with the whole lung mRNA results. In a separate
      experiment, we used a rat zymosan infectivity model to induce a pulmonary
      immunomodulatory response and determined cytokine concentrations in recovered BAL
      fluid by ELISA and two different types of cytometric bead-based assays, CBA and
      FlowCytomix (FC). The sample-to-sample correlation was good between ELISA and CBA
      with correlation coefficient R values of 0.76, 0.66, and 0.92 for rat IFN-gamma,
      TNF-alpha, and IL-6, respectively. ELISA only correlated significantly with the
      FC assay for TNF-alpha with R=0.43. Patterns of cytokine response in our rat
      model also differed among the assays but overall, the ELISA and CBA yielded
      similar results. For a method-to-method comparison, we assayed supplied cytokine
      standards from ELISA kits using both ELISA and CBA to determine the R values and
      found it to be greater than 0.90 for all the cytokines tested. It was found that
      the ELISA was more sensitive in the low range of the standard curve while the
      bead assays were capable of detecting higher protein concentrations, which would
      allow for direct measurement of concentrated samples. There was a lack of
      agreement between the absolute protein values for the ELISA and flow cytometric
      bead-based assays; in most cases, the latter method tended to give higher protein
      concentrations than ELISA. In conclusion, direct comparisons between absolute
      protein values did not agree among the assays tested in this study, but patterns
      of cytokine response generally agreed between ELISA and CBA. In the case of the
      mouse CBA, a companion measurement is recommended if samples with low
      concentrations of an analyte are reported and extrapolated below sensitivity or
      zero.

PMID- 18089293
TI  - Less increase of BNP and NT-proBNP levels in obese patient with decompensated
      heart failure: interpretation of natriuretic peptides in obesity.
AB  - OBJECTIVE: Plasma brain natriuretic peptide (BNP) is a useful adjunct to diagnose
      and monitor patient with heart failure, but there are comorbidities such as
      chronic kidney disease or chronic pulmonary disease, which influence the
      interpretation of BNP levels. PATIENT: We present a case of a young and very
      obese patient (body mass index [BMI] 72.6 kg/m(2)), who was presented with acute
      global heart decompensation. Echocardiography revealed a dilated left ventricle
      with an ejection fraction of 20% by global distributed heart with enlarged right
      heart caves. Computed tomography and X-ray demonstrated an extreme cardiomegaly
      with cardio-thoracic ratio of 0.71. Remarkably, laboratory measurements revealed
      only a slight elevated concentrations of brain natriuretic peptide (BNP) (443.2
      pg/ml) and his inactive component NT-proBNP (1710 pg/ml). Despite maximized heart
      care clinical condition of the patient aggravated continuously so that the
      patient died after 6 days because of heart insufficiency. CONCLUSION: Obese
      patients (body mass index [BMI] >30 kg/m(2)) with any given severity of heart
      failure obviously express lower levels of BNP. Until now, the cause for this
      phenomenon is unclear. Therefore caution should be exercised in interpreting BNP
      levels in such patients.

PMID- 18089292
TI  - Conserved themes in target recognition by the PAH1 and PAH2 domains of the Sin3
      transcriptional corepressor.
AB  - The recruitment of chromatin-modifying coregulator complexes by transcription
      factors to specific sites of the genome constitutes an important step in many
      eukaryotic transcriptional regulatory pathways. The histone deacetylase
      associated Sin3 corepressor complex is recruited by a large and diverse array of
      transcription factors through direct interactions with the N-terminal PAH domains
      of Sin3. Here, we describe the solution structures of the mSin3A PAH1 domain in
      the apo form and when bound to SAP25, a component of the corepressor complex.
      Unlike the apo-mSin3A PAH2 domain, the apo-PAH1 domain is conformationally pure
      and is largely, but not completely, folded. Portions of the interacting segments
      of both mSin3A PAH1 and SAP25 undergo folding upon complex formation. SAP25 binds
      through an amphipathic helix to a predominantly hydrophobic cleft on the surface
      of PAH1. Remarkably, the orientation of the helix is reversed compared to that
      adopted by NRSF, a transcription factor unrelated to SAP25, upon binding to the
      mSin3B PAH1 domain. The reversal in helical orientations is correlated with a
      reversal in the underlying PAH1-interaction motifs, echoing a theme previously
      described for the mSin3A PAH2 domain. The definition of these so-called type I
      and type II PAH1-interaction motifs has allowed us to predict the precise
      location of these motifs within previously experimentally characterized PAH1
      binders. Finally, we explore the specificity determinants of protein-protein
      interactions involving the PAH1 and PAH2 domains. These studies reveal that even
      conservative replacements of PAH2 residues with equivalent PAH1 residues are
      sufficient to alter the affinity and specificity of these protein-protein
      interactions dramatically.

PMID- 18089294
TI  - Detection of infarct-related myocardial edema using cardiac diffusion-weighted
      magnetic resonance imaging.
AB  - A 50-year-old male was admitted to our hospital complaining of chest pain and was
      diagnosed with acute myocardial infarction of the lateral wall. Coronary
      angiography revealed an occlusion in the left circumflex coronary artery, which
      was successfully reperfused. Three days after reperfusion, cardiac magnetic
      resonance imaging was performed. Black-blood T2-weighted images (T2WIs) showed an
      area of slightly increased signal intensity (SI) in the lateral wall that was
      identified as infarct-related myocardial edema. Diffusion-weighted images (DWIs)
      acquired using a low b-value single-shot echo-planar sequence with combined
      cardiac and respiratory gating revealed an area of significantly increased SI in
      the same region identified as myocardial edema on T2WIs. The contrast-to-noise
      ratios of DWIs (76.9) was significantly higher than those of T2WIs (27.0). Our
      findings indicate that DWIs may provide better contrast in infarct-related
      myocardial edema than T2WIs.

PMID- 18089295
TI  - What determines drug solubility in lipid vehicles: is it predictable?
AB  - Lipid-based drug delivery systems are of increasing interest to the
      pharmaceutical scientist because of their potential to solubilize drug molecules
      that may be otherwise difficult to develop. The ability to predict lipid
      solubility is an important step in being able to identify the right excipients to
      solubilize and formulate drugs in lipid formulations. However, predicting lipid
      solubility is complicated by the fact that interfacial effects may play a
      dominant role in these mixtures and the solubility may be affected by the
      microstructure (microemulsions, emulsions, oily solutions, etc.), as well as by
      the physicochemical properties of the oil, surfactant, co-solvent, and the drug.
      This review illustrates the fundamental factors that govern solubility in lipid
      mixtures and discusses models built at varying levels of sophistication to
      estimate the solubility. Examples from the literature are presented that
      demonstrate the application of these models, how their choice is related to the
      drug/lipid employed, and the challenges involved in solubility prediction. New
      data on the role water plays in altering lipid solubility, not only through its
      interaction with the solute, but also by changing the structure of lipids by
      promoting lipid organization are highlighted. The available data demonstrate that
      a rational understanding of solubilization in lipids is a worthwhile pursuit and
      models to predict at least the relative solubility from chemical structure have
      potential. Prediction of absolute solubility is more difficult as it requires
      knowledge of the drug's escaping tendency from the crystalline state. In recent
      years, it has become amply clear that for polar solutes, specific interactions
      are a critical factor governing solubility. Methods that can better take into
      account the specific as well as non-specific interactions between the solute and
      solvent, and the lipid microstructure, hold considerable promise for the future.

PMID- 18089296
TI  - Foetal growth determines cerebral ventricular volume in infants The Generation R
      Study.
AB  - The cerebral ventricular system is a marker of brain development and a predictor
      of neurodevelopmental outcome. In premature or dysmature neonates,
      neuroanatomical structures including the ventricular system appear to be altered.
      The present study aims to provide information on the association between foetal
      growth and neonatal cerebral ventricular size in the normal population. Within
      the Generation R Study, a population-based cohort study, we used three
      dimensional cranial ultrasound to determine lateral ventricular volume in 778
      term infants aged 4-12 weeks. Foetal growth characteristics were repeatedly
      measured in early, mid- and late pregnancy and analysed in relation to
      ventricular volume divided by head circumference. Results revealed positive
      associations between foetal head circumference in late pregnancy and log
      transformed ventricular volume (beta=0.077, 95% confidence interval (0.017;
      0.136), equivalent to a 7.7% increase in ventricular volume per standard
      deviation of head circumference). Similarly, in a per week-longer gestational
      duration, ventricular volume in infancy was 6.0% larger. Multilevel modelling
      demonstrated that reduced growth of foetal head circumference and biparietal
      diameter during pregnancy were associated with decreased ventricular volume in
      infancy. In conclusion, foetal maturation is positively associated to cerebral
      ventricular size in term infants. Larger ventricular size in term infants needs
      to be distinguished from ventricular enlargement due to intraventricular
      haemorrhage or white matter damage in premature or dysmature infants. Moreover,
      the naturally occurring enlargement of ventricles during infancy should be
      considered in interpreting reports on increased ventricular volumes in several
      neuropsychiatric disorders.

PMID- 18089297
TI  - Abnormal connections in the supraspinal bladder control network in women with
      urge urinary incontinence.
AB  - The regions of the supraspinal network that controls urinary bladder behavior are
      well known, but little is known about their interconnections. We tested the
      feasibility of using physiophysiological interaction to explore the effective
      connections of the network and to seek disease-related differences in
      connectivity. This was a secondary analysis of fMRI data obtained from women aged
      26-85 years, 11 with urge urinary incontinence and 10 with normal bladder
      function. In each subject, fMRI BOLD images were obtained during a period with
      full bladder and strong bladder sensation (without detrusor overactivity) while
      repeatedly infusing and withdrawing a small amount of liquid in and out of the
      bladder. Regions of interest included right insula (RI) and anterior cingulate
      gyrus (ACG), both consistently involved in bladder control. Other regions
      effectively connected to them were identified by significant correlation between
      their fMRI signal and the interaction RIxACG. Among normal subjects, many regions
      involved in bladder control were effectively connected with RI/ACG, including
      frontotemporal and sensorimotor cortex, forebrain, midbrain and pontine regions.
      The sign of the correlation with RIxACG was near-uniformly positive, perhaps
      suggesting mainly inhibitory connections. Among urge-incontinent subjects, the
      effective connectivity was shifted to a parieto-temporal complex, while the sign
      of the correlation was predominantly negative, perhaps consistent with excitation
      (recruitment) of accessory pathways in an attempt to maintain bladder control.
      Thus, physiophysiological interaction yields potentially important information
      about the connectivity of the bladder control network and its changes in disease.

PMID- 18089298
TI  - Proliferation signal inhibitors in transplantation: questions at the cutting edge
      of everolimus therapy.
AB  - While advances in immunosuppressive therapy have allowed dramatic improvements in
      the control of acute allograft rejection, there is still a need to improve long
      term graft and patient survival rates following renal and heart transplantation.
      Among the recognized threats to long-term organ survival are chronic allograft
      dysfunction in the form of chronic allograft nephropathy and cardiac allograft
      vasculopathy, with long-term patient morbidity and mortality further compromised
      by higher than normal rates of posttransplant cardiovascular disease, infection,
      and malignancy. A growing body of evidence finds that the selection and dosing of
      immunosuppressive therapies can have great influence on long-term transplantation
      outcomes. Early evidence suggests that the proliferation signal inhibitors
      (PSIs), everolimus and sirolimus, might offer effective immunosuppressive
      activity together with antiproliferative effects that may address some of the
      unmet needs in the long-term therapeutic management of the posttransplant
      patient. This review summarizes the emerging evidence for employing PSI-based
      immunosuppression to seek a balance between the goals of maximizing graft and
      patient survival, while minimizing the risks of adverse events and long-term
      complications. Based on the proceedings of an international gathering of
      nephrologists, cardiologists and surgeons at the inaugural PSI Forum meeting
      "Proliferation signal inhibitors in transplantation: questions at the cutting
      edge," this paper aims to provide both an evidence base and practical guidance
      for transplant physicians seeking to optimize their use of PSI treatment and
      highlights avenues of ongoing research into the clinical potential of this class
      of immunosuppressive therapy.

PMID- 18089299
TI  - The Tuscany model of a regional transplantation service authority: Organizzazione
      Toscana Trapianti.
AB  - In 2003, the Tuscan Regional Government appointed a transplantation service
      authority to reorganize all regional donation and transplantation activities: the
      Organizzazione Toscana Trapianti (OTT). Herein we have presented a retrospective
      review of deceased donation and transplantation activities from 1993 until 2006
      in Tuscany to illustrate the results of OTT activity and the methodology in
      reorganizing the regional network. After the advent of OTT, the mean rate of
      recovered deceased donors (DDs) rose from 16.9+/-7.7 per million population (pmp)
      to 32.7+/-4.3 pmp (Delta=+93.4%); multiorgan DDs increased by 48.6%, from a mean
      of 12.8+/-5.2 pmp to 21.1+/-2.9 pmp, despite a 55.2% increase in recovered
      DDs>or=60 years. Recovered DD solid organs rose by 78.4% after the advent of OTT
      (from a mean of 53+/-20.1 pmp to 89.5+/-13.6 pmp), and the number of DD organ
      transplants rose by 87.3% (ie, from a mean of 49.9+/-23.9 to 91.9+/-5.2 pmp). The
      experience of OTT showed that an efficient regional network requires a global
      approach to donation and transplantation, according to the principles of clinical
      governance. A region-based model, whereby health care professionals share
      clinical governance with regional authorities and regional networks integrated at
      a national level, may prove favorable not only to increase donor procurement
      rates but also to improve the quality of the whole transplantation care process.

PMID- 18089300
TI  - Gender bias in renal transplantation: are women alone donating kidneys in India?
AB  - Previous studies have shown that women not only donate live-related and unrelated
      kidneys more often, but are also less likely to receive a live kidney than men.
      Few data are, however, available from developing countries. To study a possible
      gender imbalance in living donor (LD) renal transplantation in India, we
      retrospectively analyzed all LD renal transplantations performed at a single
      center between 2001 and 2005. Of the 682 recipients, 606 (88.9%) were males and
      76 (11.1%) were females (P<.0001). There were 552 biologically related, 118
      spousal, and 12 unrelated nonspousal donors. Among the donors, there were 451
      (66.1%) females and 231 (33.9%) males (P<.001). Most of the live donations were
      contributed by mothers (32.1%). In the spousal group, the greatest gender
      disparity was observed with predominantly wives donating for their husbands
      (90.7% vs 9.3%). Complex social and economic factors are responsible for the
      overall gender imbalance. In conclusion, women represent a highly vulnerable
      group in LD renal transplantation. Awareness and changes in attitudes of the
      public as well as physicians are needed to eliminate this gender inequity.

PMID- 18089301
TI  - Donor brain death mechanisms and outcomes after heart transplantation.
AB  - We sought to explore whether the cause of donor brain death influenced recipient
      outcomes after cardiac transplantation. In retrospect, 358 consecutive donors
      provided cardiac allografts to adult patients undergoing orthotopic heart
      transplantation at a single urban US medical center from January 2000 through
      December 2005. Alternate recipients were excluded. Mechanism and cause of donor
      brain injury and death were divided into five categories: anoxia (nontraumatic)
      (n=36), blunt head trauma (n=220), penetrating head trauma (n=83), brain
      tumor/infection (n=7), and cerebrovascular event (n=12). The five subgroups were
      categorized as traumatic or nontraumatic. The end points of the study were causes
      of early and late mortality, survival, and rejection rate. There were 59 deaths
      in the 6-year period. Total and short-term recipient mortality were found to be
      statistically higher among heart transplant recipients when the donors suffered
      from traumatic brain death compared to those whose brain death etiology was
      nontraumatic (P=.045, P=.033, respectively). Rejection rate was similar in all
      groups (P=.497). In conclusion, donor traumatic brain death was found to be a
      valid risk factor for recipient mortality after heart transplantation. Caution
      should be used when evaluating such donors, particularly in the presence of other
      risk factors.

PMID- 18089302
TI  - Relationship between procalcitonin values and infection in brain-dead organ
      donors.
AB  - BACKGROUND AND AIMS: An association between the inflammatory reactions estimated
      by several biomarkers and organ dysfunction has been reported in brain-dead organ
      donors (BDOD). Procalcitonin (PCT), a biomarker of inflammation due to bacterial
      infection, is increased among BDOD. However, is not known whether infection
      changes PCT values in BDOD. MATERIALS AND METHODS: We retrospectively analyzed 82
      BDOD including several demographic and clinical parameters, bacterial culture
      results, antibiotics prescription, and plasma values of PCT measured before organ
      harvesting. Infection was diagnosed to be either a positive bacterial culture
      (restricted definition) and/or prescription of antibiotics (extended definition).
      RESULTS: The median PCT value was 1.5 (interquartile range [IQR], 0.4 to 6.9;
      range, 0 to 526 ng/mL; n=82). Thirty-eight (46%) and 24 (29%) patients had PCT
      values>2 ng/mL and >5 ng/mL, respectively. Median PCT values among infected
      (1.18; IQR, 0.27 to 6.55 ng/mL) versus noninfected (1.57; IQR, 0.53 to 7.15
      ng/mL) BDOD (restricted definition) were not different (P=.36). The area under
      the receiver operating characteristic curve using PCT to predict infection
      (restricted definition) was 0.52. Specificity of PCT to predict infection was
      above 80% at PCT values>9 ng/mL. CONCLUSION: Our results confirmed PCT values are
      increased in BDOD, suggesting that this was not related to an infectious cause
      (whatever definition was used) unless PCT values are high.

PMID- 18089303
TI  - Technical complications in organ procurement.
AB  - It is of crucial importance that harvested organs are not discarded because of
      lesions inflicted during the procurement operation. From January 2005 to January
      2006, a total of 395 organs were procured: 266 kidneys, 102 livers, and 27
      pancreas. Two kidneys were lost due to vascular lesions, and 1 liver could not be
      transplanted because of a severe parenchymal injury (0.75% total organ losses).
      In 33 of 198 cases (16.7%) despite lesions to renal vessels or to the ureter, the
      kidneys were transplanted after back-table repair procedures. Vascular lesions
      were observed in 10% of the evaluated livers (8 of 102) and in 3 of 18 pancreatic
      grafts. In the literature, a total organ loss of 0.75% because of technical
      problems demonstrates a high standard of visceral organ procurement in our
      region. Hence, reparable vascular and ureteral lesions in 10% to 16.4% indicated
      the need for better surgical training and standardization in procurement
      techniques. We believe that double-checking both the organ and quality reports
      and giving immediate feedback to the procurement surgeons in cases of technical
      problems are effective ways to perform quality control. It must be our goal to
      increase the response rate of the quality forms.

PMID- 18089304
TI  - Complications in the right lobe adult living donor: single-center experience in
      China.
AB  - INTRODUCTION AND OBJECTIVE: Living donor liver transplantation (LDLT) has been
      accepted as an established treatment modality for end-stage liver diseases to
      alleviate the shortage of cadaveric organs. Reported complication rates for right
      lobe adult living donors vary, but are estimated to be approximately 35% with a
      surgical mortality rate of approximately 0.3%. Our objective was to evaluate the
      complications in right lobe adult living donors in a single center. MATERIALS AND
      METHODS: This retrospective review includes 62 adult living donors who underwent
      right hemi-hepatectomy between January 2002 and December 2006. Eighteen donors
      were men and 44 were women (range, 18-65 years; median age, 36 years). The mean
      follow-up time for the donors was 16 months (range, 3 months-4 years). RESULTS:
      All donors were alive and well at the end of the study period. Complications
      included pleural effusion (n=6; 9.68%), bile leaks (n=3; 4.84%), wound infection
      (n=2; 3.23%), pneumonia (n=2; 3.23%), chyle leak (n=1; 1.61%), intra-abdominal
      bleeding (n=1; 1.61%), subphrenic effusion (n=1; 1.61%), portal vein thrombosis
      (n=1; 1.61%), and chylothorax (n=1; 1.61%). There was no donor mortality, and the
      overall complication rate was 29%. CONCLUSIONS: The overall complication rate in
      the right lobe adult living donor was 29% in our center; there was no donor
      mortality. These complications could be avoided or overcome through intensive
      postoperative surveillance.

PMID- 18089305
TI  - The effect of body temperature in a rat model of renal ischemia-reperfusion
      injury.
AB  - BACKGROUND: Renal ischemia-reperfusion injury (IRI) is an unavoidable event in
      renal transplantation; the effects of IRI can be seen in both the acute and long
      term function of the transplanted organ. For this reason, research into the
      pathophysiology of ischemia-reperfusion is at the forefront of transplantation
      research. Animal models, particularly in the rat, provide a useful research tool
      in studying the intricacies of IRI and in evaluating new treatments. We describe
      a model of right nephrectomy and left renal clamping for 45 minutes and
      demonstrate the effects of temperature variation during the ischemic period.
      METHODS: Male Sprague-Dawley rats (under isoflurane anesthesia) underwent
      bilateral flank incision with removal of the right kidney and clamping of the
      left renal hilum for 45 minutes. The animals were divided into 3 groups (n=6):
      group 1 had the procedure performed on a heating mat with no temperature control
      facilities, group 2 used no heating mat, and group 3 used a rectal temperature
      controlled homeothermic blanket system (Harvard Medical, United Kingdom).
      Temperature was taken every 5 minutes throughout the procedure and blood samples
      were taken on a daily postoperative basis via tail vein venepuncture. RESULTS:
      The average temperature at the end of the procedure in group 1 was 39.67 degrees
      C and the creatinine level at day 3 was 574+/-17.84, in group 2 the temperature
      was 32.6 degrees C and the creatinine level was 115+/-4.06, and in group 3 the
      temperature was maintained between 36.5 degrees C-37 degrees C and the serum
      creatinine level was 329+/-19.18. The temperature of the animal during the
      ischemia phase of IRI significantly affects the severity of injury. Relative
      hyperthermia resulted in more severe renal injury and unrecoverable acute renal
      failure, no source of heat led to a relative hypothermia, and reduction of renal
      injury. Use of the homeothermic heating blanket led to an increase in creatinine
      level by day 3, indicating a significant ischemic stimulus; however, by day 10
      the creatinine level had returned to normal. CONCLUSION: This illustrates the
      importance of temperature as a variable in animal models of IRI and thus should
      be clearly stated in all experimental methods to ensure an appropriate ischemic
      stimulus and for adequate comparisons between various therapeutic interventions.

PMID- 18089306
TI  - Pharmacological induction of heme oxygenase-1 inhibits iNOS and oxidative stress
      in renal ischemia-reperfusion injury.
AB  - Nitric oxide (NO), produced by nitric oxide synthase, is implicated in the
      pathophysiology of renal ischemia/reperfusion (I/R) injury. This study sought to
      elucidate the impact of pharmacological induction of heme oxygenase-1 (HO-1) on
      renal I/R injury. Rats were subjected to 45 minutes of renal ischemia followed by
      various times of reperfusion (30 minutes, 1 hour, or 3 hours). Plasma from
      sacrificed rats was obtained, and the kidneys processed for the expression of
      iNOS, cleaved caspase-3, p38MAPK and for immunohistochemical analysis.
      Furthermore, we determined renal and plasma levels of lipid hydroperoxides, total
      thiol groups, and plasmatic NO2-/NO3- formation. Our results showed a time
      dependent increase in iNOS expression, which was also confirmed by increased
      plasma formation of NO2-/NO3-. Interestingly, this effect was reversed by
      pretreatment (12 hours) with SnCl2, a potent and specific inducer of renal HO-1
      expression and activity, or by intraperitoneal injection of biliverdin (10
      mg/kg). Furthermore, we observed a concomitant reduction in plasma and renal LOOH
      formation, a normalization of renal total thiol content, a reduction of caspase-3
      mediated apoptosis, and a significant increase in p38MAPK phosphoration. Taken
      together, these results suggested that HO-1 and its byproduct biliverdin play
      major roles in the pathophysiological cascade leading to renal I/R injury.

PMID- 18089307
TI  - FTY720 reduces extracellular matrix expansion associated with ischemia
      reperfusion induced injury.
AB  - BACKGROUND: Ischemia-reperfusion (IR) is one of the strongest nonimmune factors
      associated with the development of chronic allograft nephropathy (CAN). This
      effect is often exacerbated by immunosuppressive medications, most notably
      cyclosporine. Although traditionally the macrophage was thought to stimulate
      fibroblast activity in CAN, recent evidence supports a role for lymphocytes.
      FTY720 is a new immunosuppressant that promotes lymphocyte sequestration into
      lymph nodes and Peyer's patches. This study investigated the effect of FTY720 on
      renal fibrosis in the rat following an IR insult (IRI). METHODS: A rat model of
      IRI was used in which male Sprague-Dawley rats (under isoflurane anaesthesia)
      underwent bilateral flank incision with removal of the right kidney and clamping
      of the left renal hilum for 45 minutes. Five groups of animals were studied
      (n=4): nephrectomy only, IRI only, IRI+FTY720 (1 mg/kg/d), IRI+cyclosporine (15
      mg/kg/d), and IRI+FTY 720 (1 mg/kg/d) and cyclosporine (15 mg/kg/d). Animals were
      humanely killed at 30 days. RESULTS: Serum creatinine (SCr) level was
      significantly reduced in the FTY720-treated animals. IRI alone produced a
      significant increase in SCr level compared with neprectomized animals (138
      micromol/L vs 55 micromol/L; P<.05). This effect was potentiated by treatment
      with cyclosporine (173 micromol/L vs 55 micromol/L; P<.05). Treatment with FTY720
      significantly reduced SCr level in rats following IRI alone (81 micromol/L vs 138
      micromol/L; P<.01) and in rats following IRI + cyclosporine (98 micromol/L vs 173
      micromol/L; P<.014). Parallel changes were seen in the levels of proteinuria.
      Fibrosis was assessed using Masson's trichrome (MT) staining. IRI alone produced
      a significant increase in MT staining compared with nephrectomized animals (0.92
      vs 0.03; P<.05). This effect was potentiated by treatment with cyclosporine (1.12
      vs 0.92; P=.022). Treatment with FTY720 reduced the level of MT staining in rats
      following IRI alone (0.34 vs 0.92; P<.05) and in rats following IRI+cyclosporine
      (70.34 vs 1.12; P<.05). Levels of TGF-beta1 were considerably reduced in FTY720
      treated animals (compared with cyclosporine+IRI and IRI only), either alone
      (196+/-31 pg/mL vs 1105+/-59 pg/mL and 611+/-38; P<.05) or in conjunction with
      cyclosporine (423+/-26 pg/mL vs 1105+/-59 pg/mL and 611+/-38; P<.05). CONCLUSION:
      Our study shows that treatment with FTY720 can reduce renal fibrosis as a result
      of IRI, both alone and in conjunction with cyclosporine. This provides promising
      evidence for using FTY720 in a calcineurin-free or reduced-dose immunosuppression
      protocol in an effort to reduce the incidence of CAN.

PMID- 18089308
TI  - Comparison of the effects of sodium nitroprusside and L-carnitine in experimental
      ischemia-reperfusion injury in rats.
AB  - AIM: The aim of this study was to evaluate the protective effect of sodium
      nitroprusside (SNP) as a nitric oxide (NO) donor and L-carnitine intraperitoneal
      administration to treat experimental ischemia-reperfusion (I/R) in rats.
      MATERIALS AND METHODS: Rats were divided into four groups, each one consisting of
      10 animals. Group 1 was subjected to a sham operation. In group 2, an I/R process
      was applied to the rats. In group 3, SNP (5 mg/kg) and in group 4, L-carnitine
      (500 mg/kg) was administered in addition to the I/R process. Ileal tissue samples
      were obtained for analysis of tissue malonyl dialdehyde (MDA) and for
      histopathologic examination. RESULTS: By histopathologic examination, the I/R
      group showed a significant difference from the SNP and L-carnitine groups
      (P<.05). There was no difference between the sham, the SNP, and the L-carnitine
      groups (P>.05). SNP used as an NO donor produced a significant decrease in MDA
      levels. There was a significant difference between the MDA levels of the SNP and
      the I/R groups (P<.05). Also, the difference between this group and the I/R group
      was significant (P<.05). CONCLUSION: SNP helped to both prevent and reduce
      mucosal damage in terms of histological and tissue MDA levels. Since the results
      of the L-carnitine group and the SNP group were similar, L-carnitine was as
      effective as exogenous NO.

PMID- 18089309
TI  - Protective effects of MnM2Py4P and Mn-salen against small bowel
      ischemia/reperfusion injury in rats using an in vivo and an ex vivo electron
      paramagnetic resonance technique with a spin probe.
AB  - BACKGROUND: Reperfusion of ischemic tissues results in the formation of toxic
      reactive oxygen species (ROS), such as superoxide anion, hydroxyl radicals,
      hydroperoxide, and peroxynitrite. ROS are potent oxidizing agents, capable of
      damaging cellular membranes by lipid peroxidation. In the present study, we
      applied an in vivo electron paramagnetic resonance (EPR)/spin probe and an ex
      vivo EPR technique to provide direct evidence of ROS following experimentally
      induced small bowel ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: We
      used a rat model of small bowel I/R injury to explore the possibility that
      MnM2Py4P or Mn-salen can prevent the accumulation of ROS species following
      experimentally induced I/R injury. We examined the ability of MnM2Py4P and Mn
      salen to scavenge radicals in living Sprague-Dawley (SD) rats using an in vivo
      and an ex vivo EPR technique with a spin probe. RESULTS: The CP decay rates in
      the MnM2Py4P- and Mn-salen-treated rats were significantly higher than those in
      the untreated rats and almost equal to those in sham group rats. There were no
      significant differences between the MnM2Py4P-treated group and the Mn-salen
      treated group. Superoxide scavenging activities (SSA) in the MnM2Py4P- and EUK-8
      treated group were higher than those in the untreated group and almost equal to
      the sham group. CONCLUSION: The present study suggested that the protective
      effects of MnM2Py4P and Mn-salen against small bowel IR injury were mediated by
      the inhibition of O2, H2O2, and NO production.

PMID- 18089310
TI  - Real-time monitoring of nitric oxide (NO) and pO2 levels under ischemic
      conditions associated with small bowel ischemia/reperfusion injury using
      selective electrodes for NO and oxygen molecules.
AB  - The present study demonstrated the feasibility of monitoring nitric oxide (NO)
      and pO2 levels under ischemic conditions associated with small bowel
      ischemia/reperfusion (I/R) injury through the use of selective electrodes for NO
      and oxygen molecules. NO levels gradually increased during ischemia. When
      reperfusion was started, the NO level decreased suddenly and returned to pre
      ischemia values within 10 minutes. After clamping, pO2 decreased rapidly. When
      reperfusion was started, pO2 increased suddenly, returning to pre-ischemia values
      within 10 minutes. We concluded that it is feasible to monitor NO and pO2 levels
      under ischemic conditions of small bowel I/R injury through the use of electrodes
      selective for NO and oxygen molecules.

PMID- 18089311
TI  - Ischemic preconditioning and intermittent clamping increase the tolerance of
      fatty liver to hepatic ischemia-reperfusion injury in the rat.
AB  - INTRODUCTION: Liver ischemia-reperfusion (I/R) injury is a well-known cause of
      morbidity and mortality following liver surgery and transplantation. Hepatic
      steatosis increases the extent of cellular injury incurred during I/R injury. We
      sought to identify measures that reduced the untoward sequelae of liver I/R
      injury. METHODS: Male Zucker rats were subjected to 75 minutes of 70% hepatic
      ischemia, and 3 hours of reperfusion. The ischemic periods were based on the
      following protocols: continuous clamping (CC) for 75 minutes; intermittent
      clamping (IC) with five cycles of 15 minutes clamp on and 5 minutes clamp off; or
      ischemic preconditioning (IP) with 10 minutes clamp on, 15 minutes off, and 60
      minutes on (n=7 in each group). Warm I/R injury was evaluated using serum levels
      of aspartate aminotransferase (AST), serum interleukin (IL)-6, as well as
      hematoxylin and eosin staining. RESULTS: Hepatocellular injury was significantly
      reduced with IP or IC compared with CC (AST: 3285+/-122.3 and 2875+/-285.4
      compared with 5436.3+/--984.7 units/L, respectively; P<.01). Serum IL-6 level was
      also significantly reduced with IP and IC compared with CC (70+/-8.8 and 76+/-6.2
      compared with 147+/-8.5 ng/l, respectively (p<.01). Histological analysis also
      revealed that IC and IP provided significant protection compared with the CC
      group. CONCLUSION: IC and IP increased the tolerance of a fatty liver to hepatic
      I/R injury.

PMID- 18089312
TI  - Hepatic reperfusion in rats: a new model with portal arterialization in studying
      early ischemia-reperfusion injury.
AB  - Isolated liver perfusion has been used to evaluate the beneficial effects of
      several agents. In the present study, we developed a model using a recipient rat
      to reperfuse harvested livers in an ex situ, in vivo recirculating system. A
      total of 25 reperfusion procedures using adult male Wistar rats as donors and
      recipients were done. The preservation of the livers was performed with
      University of Wisconsin solution for 6 hours. Thereafter, the liver was
      reperfused with blood from another rat. We believe that the model presented
      herein offers an alternative method to evaluate early hepatocellular damage or
      hepatic microcirculation.

PMID- 18089313
TI  - Two-layer method (UW solution/perfluorochemical plus O2) for lung preservation in
      rat lung transplantation.
AB  - A new preservation method using perfluorochemicals (PFC) with oxygen administered
      continuously was developed for lung preservation and compared with traditional
      cold preservation methods for rat lung transplantation. Male Sprague-Dawley rats
      underwent orthotopic left lung transplantations of grafts preserved in lactiated
      Ringers solution (LR), University of Wisconsin solution (UW), Celsior solution,
      or a two-layer (PFC plus O2) solution for 6 hours. One hour after reperfusion,
      the right pulmonary artery and bronchus were clamped and 5 minutes later we
      recorded peak airway pressure and PaO2 level. The isograft was excised for
      measurement of myeloperoxidase activity, wet-to-dry ratio, and histologic
      examination to evaluate isograft function. The mean peak airway pressure was
      29.80+/-6.72 mm H2O in the LR group, 28.80+/-5.76 mm H2O in the UW group, 33.60+/
      5.17 mm H2O in the Celsior group, and 32.40+/-2.60 in the two-layer group. The
      mean PaO2 level was 99.78+/-76.09 mm Hg in the LR group, 87.84+/-33.58 mm Hg in
      the UW group, 104.50+/-72.93 mm Hg in the Celsior group, and 62.08+/-31.34 mm Hg
      in PFC and UW solution plus O2 group (two layers). The mean net myeloperoxidase
      activity OD level was 0.110+/-0.104 in the LR group, 0.392+/-0.328 in the UW
      group, 0.351+/-0.620 in the Celsior group, and 0.532+/-0.616 in the two-layer
      group. The mean wet-to-dry ratio was 7.47+/-1.60 in the LR group, 6.56+/-0.62 in
      the UW group, 7.54+/-2.19 in the Celsior group, and 5.32+/-2.20 in the two-layer
      group. The differences between groups in these parameters were not significant.
      Upon histologic examination, more inflammatory cell aggregates were seen in the
      two-layer group, less in the LR and the Celsior groups. The function of the lung
      graft after 6 hours of storage was not better using this two-layer method for
      preservation than traditional preservation methods in rat lung transplantation.
      Histologic examination revealed more inflammatory cell aggregates in the lung
      graft preserved using a two-layer method.

PMID- 18089314
TI  - Possible role of hydrogen sulfide on the preservation of donor rat hearts.
AB  - OBJECTIVE: The aim of this study was to observe the preservative effect of
      hydrogen sulfide (H2S) on donor rat hearts. MATERIALS AND METHODS: The hearts of
      24 Sprague-Dawley rats were perfused on a Langendorff perfusion column for 30
      minutes. We calculated and recorded the left ventricular-developed pressure
      (LVDP), and positive and negative derivatives of left ventricular systolic
      pressure (LVSP; +dP/dt and -dP/dt). Hearts were then arrested and stored for 6
      hours at 4 degrees C: group 1, Krebs-Henseleit (KH) solution; group 2, KH
      solution with 1 micromol/L NaHS; group 3, KH solution with 1 micromol/L NaHS and
      10 micromol/L glibenclamide; group 4, St. Thomas II solution. Hearts were
      transferred back to the Langendorff column. After stabilizing for 30 minutes, LV
      performance was assessed as before. The donor hearts were kept for pathological
      study including myocardial water ratio, ATP content, and myocyte apoptosis index.
      RESULTS: The recovery rates of +dp/dtmax, -dp/dtmax, and LVDP of groups 2 and 4
      were much better than those of groups 1 and 3. The hearts contracted immediately
      after reperfusion in group 4. Ventricular fibrillation was seen before
      contraction in the other 3 groups, with the longest duration in group. No
      significant difference in myocardial water ratio was found. The ATP content was
      the highest in group 2. Apoptosis was observed in the 4 groups with the lowest
      apoptosis index in group 2. CONCLUSIONS: H2S has a protective effect on rat donor
      hearts at the concentration of 1 micromol/L. The protective effect is better than
      that of St. Thomas II solution. The protective effect of H2S can be blocked by
      glibenclamide.

PMID- 18089315
TI  - Effect of cryopreservation on the immunogenicity of osteoblasts.
AB  - BACKGROUND: Tissue-engineered bone is the most perspective and ideal prosthesis
      for bone defects. But the immunological reaction in allograft is unavoidable. To
      date there has not been an analysis of the effect of cryopreservation on
      osteoblast immunogenicity. In this study, we investigated the effects of fluid
      nitrogen cryopreservation on immunogenicity of osteoblasts. MATERIALS AND
      METHODS: The osteoblasts were harvested and cultured from the tibial periosteum
      of New Zealand rabbits, examined by alkaline phosphatase (ALP) and alizarin red S
      stains, and then cryopreserved for 90 days. Cryopreserved (group C) and fresh
      (group F) osteoblasts were labeled by the immunofluorescene technique, and the
      MHC class I antigen was examined by flow cytometric (FC) assay. At the same time,
      by establishing an osteoblast and lymphocyte mixed culture model (OLMC), the
      immunogenicity of osteoblasts was examined. RESULTS: The positive rate of MHC
      class I antigen in group F was 46.36%+/-3.15%, while in group C it was 26.43%+/
      2.57%. The MHC I antigen expression was significantly stronger in fresh cells
      than that in cryopreserved ones (P<.01). In the OLMC assay, the stimulation index
      (SI) of group F was 3.55+/-0.78, which was significantly higher than that of
      group C (1.83+/-0.41; P<.01). CONCLUSIONS: The FC assay and OLMC experiments
      showed that osteoblasts surface antigen expression and allostimulatory function
      were greatly reduced by cryopreservation. Fluid nitrogen cryopreservation is an
      ideal method to reduce the immunogenicity in allograft.

PMID- 18089316
TI  - Influence of oxidative stress and inflammation on rHuEPO requirements of
      hemodialysis patients with CRP values "in normal range".
AB  - AIMS: We sought to evaluate influences of oxidative stress (OS) on rHuEPO
      requirements in hemodialysis patients without chronic inflammation. METHODS:
      Sixty-eight hemodialysis patients and 46 healthy controls underwent measurements
      plasma levels of antioxidative agents, such as glutathione peroxidase (GPX),
      superoxide dismutase (SOD), and oxidative compounds including malonyldialdehyde
      (MDA). We retrospectively analyzed the last 3 months' rHuEPO requirements, iron
      indices, and CRP levels. RESULTS: Plasma levels for SOD, GPX, and MDA were
      974.4+/-216.4 U/gHb, 44.4+/-13.6 U/gHb, 10.0+/-2.0 nmol/mL, respectively yielding
      results that were different from healthy controls (P<.0001). Increased OS
      negatively correlated with hemoglobin levels (P<.0001) and positively correlated
      with rHuEPO requirements (P<.01). Increased antioxidative capacity positively
      correlated with hemoglobin levels (P<.0001) and negatively correlated with rHuEPO
      requirements (P<.0001). For further analyses, hemodialysis patients were
      subgrouped according to rHuEPO requirements as group I (lowest 1/3, n=23), group
      II (moderate 1/3, n=23) and group III (highest 1/3, n=22). Group III displayed
      the highest MDA (P<.05), the lowest SOD (P<.0001), and comparable GPX (P<.05)
      levels. Group III also had the highest CRP and the lowest albumin levels compared
      with the others (P<.01). CONCLUSION: OS has strong adverse influences on rHuEPO
      responses of HD patients with "normal" CRP levels, but it should not be forgotten
      that CRP levels in the "normal" range may still reflect ongoing
      microinflammation.

PMID- 18089317
TI  - Advantage of eradication therapy for Helicobacter pylori before kidney
      transplantation in uremic patients.
AB  - From January 1999 to February 2007, 61 end-stage renal disease (ESRD) candidates
      for kidney transplantation underwent an esophagogastroduodenoscopy (EGDS) to
      detect Helicobacter pylori (HP). We correlated treatment for HP before
      transplantation and upper digestive tract hemorrhagic complications and possible
      recurrence of peptic disease posttransplantation. The 32 (52.4%) HP-Positive
      cases were divided into 2 groups: (1) 17 patients who underwent treatment for the
      eradication of the infection with 40 mg/d omeprazole for 4 weeks, 500 mg
      claritromycin twice daily for 7 days, and 2 g/d amoxicillin for 7 days; and (2)
      15 untreated patients. No significant differences were found in the hemorrhagic
      erosive gastritis of patients with regard to the treated HP-Positive and
      nontreated HP-Positive patients (2 vs 3) and between the HP-negative patients and
      the nontreated HP-Positive patients (2 vs 3). The presence of gastric or duodenal
      ulcers was significantly higher in the nontreated patient than in the treated HP
      positive patients (5 vs 1; P=.05) and significantly higher in the nontreated HP
      Positive patients than in the HP-negative patients (5 vs 0; P=.05). We concluded
      that HP-positive patients should therefore be treated for the infection to avoid
      a long-term significant increase of gastric and/or duodenal peptic disease
      subsequent to renal transplantation in these immunodepressed subjects.

PMID- 18089318
TI  - Human herpesvirus-8 infection in hemodialysis patients from Sao Paulo, Brazil:
      preliminary results.
AB  - Epidemiological studies conducted in endemic areas of human herpesvirus 8 (HHV-8)
      infection have shown iatrogenic Kaposi's sarcoma in renal transplant recipients.
      Hemodialysis has not yet been demonstrated to be a route of virus
      transmission/acquisition, although recently blood transfusion has been suggested
      as a vehicle of HHV-8 transmission. The present study searching HHV-8 antibodies
      among serum samples from 70 hemodialysis patients disclosed a high prevalence of
      infection (22.9%). There was an association between HHV-8 seroreactivity and
      previous transfusions and transplantation, as well as with a black/pardum ethnic
      background of patients. These results emphasized that chronic renal patients are
      at risk of developing HHV-8-related diseases.

PMID- 18089320
TI  - Membranous glomerulonephritis may be associated with heavy marijuana abuse.
AB  - It is well documented that drug abuse can cause renal diseases. Nephropathy and
      proteinuria among heroin addicts has been recognized since the early 1970s. The
      predominant lesions in heroin-associated nephropathy are segmental
      glomerulosclerosis in African-Americans and membranous glomerulonephritis (MGN)
      in the Caucasian population. Cocaine may induce kidney damage, predominantly
      acute renal failure in the course of rhabdomyolysis. However, there are no case
      reports of nephropathy associated with marijuana smoking. We report a case of a
      marijuana-addicted 27-year-old Caucasian man after cadaveric kidney
      transplantation who developed de novo posttransplant MGN. The long period and
      high level of narcotic intoxication suggested that de novo MGN may have been
      associated with heavy marijuana abuse.

PMID- 18089319
TI  - Quality of life in hemodialysis, peritoneal dialysis, and transplantation
      patients.
AB  - Quality of life (QOL) has recently been explored as one of the main outcomes of
      renal replacement therapy. In this study, we sought to compare three groups of
      patients-hemodialysis, peritoneal dialysis, and transplantation-with regard to
      QOL. METHODS: Seventy-five hemodialysis, 41 peritoneal dialysis and 20 transplant
      patients were given Patient Information Form, Short Form Health Survey 36, Beck
      Depression Inventory, and State-Trait Anxiety Inventory. RESULTS: The QOL scores
      of the three groups were similar and lower than the normal Turkish population.
      Depression and anxiety levels had significant and negative effects on QOL of
      hemodialysis and peritoneal dialysis, but not transplant patients. In a multiple
      regression analysis, being male, being older than 46 years, living with family,
      having middle-higher income, having renal disease for a longer time, having a
      longer period of dialysis treatment, having comorbid illness, having not enough
      illness knowledge, and having higher levels of depression and of anxiety
      significantly correlated with a worse quality of life. CONCLUSIONS: The three
      forms of renal replacement therapy did not differ with regard to QOL. Among the
      factors that seem to affect QOL, psychological status and treatment/illness
      knowledge had the most significant correlation. The underlying mechanisms need to
      be clarified.

PMID- 18089321
TI  - Pretransplant donor-specific interferon-gamma ELISPOT assay predicts acute
      rejection episodes in renal transplant recipients.
AB  - Interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assay is a
      powerful tool for measuring the frequency of alloantigen-specific T cells,
      reflecting cellular immunity. We correlated the pretransplant frequencies of
      donor-specific and third-party-specific IFN-gamma ELISPOT tests, with the
      posttransplant outcomes of 45 recipients of living donor renal transplantations.
      The mean frequency of pretransplant donor-specific ELISPOT was significantly
      greater among patients with acute rejection episodes (ARE) than those without ARE
      (18.0 [12 to 50] versus 8.8 [5 to 30.4]) spots per 200,000 peripheral blood
      lymphocytes (PBLs; P=.024). A cutoff level of 12 spots per 200,000 PBLs on the
      donor-specific ELISPOT identified an ARE-positive patient with a sensitivity of
      81.8% and a specificity of 64.7%. The recipients with pretransplant donor
      specific ELISPOT+showed higher serum creatinine levels and lower glomerular
      filtration rate (GFR) at 6 posttransplant months (P<.05). Although the
      pretransplant third-party-specific ELISPOT results correlated with the donor
      specific ELISPOT results (r=.783; P<.001), there was no significant difference in
      the third-party ELISPOT results between the ARE-positive and ARE-negative
      recipients. In conclusion, an analysis of pretransplant donor-specific IFN-gamma
      ELISPOT may identify the posttransplant risk of developing ARE and displaying
      decreased GFR at 6 months.

PMID- 18089322
TI  - Preemptive transplantation and long-term outcome in living donor kidney
      transplantation, single-center experience.
AB  - Although preemptive transplantation of kidneys from living donors without the
      previous initiation of dialysis is associated with longer allograft survival in a
      USRDS cohort, the effect of pretransplantation dialysis on graft outcome is still
      controversial in Korea. The purpose of this study was to evaluate the
      differential effects on long-term outcomes of living donor kidney transplantation
      according to initiation of dialysis and its duration or no dialysis. We performed
      a retrospective cohort study of 494 patients who received a first kidney
      transplant from a living donor between 1990 and 2006. The mean duration for
      dialysis was 14.5+/-22.2 months. The 10-year patient survival of 98.0% in the
      preemptive group was not significantly higher than the dialysis group (91.2%,
      P>.05). However, 10-year graft survival was higher in the preemptive than the
      dialysis group (preemptive 94.4%, dialysis 76.5%; P<.05). The differential effect
      of pretransplant dialysis either by hemodialysis or peritoneal dialysis was not
      significant, although peritoneal dialysis as a pretransplant treatment seemed to
      be beneficial on long-term graft survival (5-year graft survival; peritoneal
      94.8% and hemodialysis 89.2%). The duration of dialysis did not affect graft
      survival in our study cohort. In conclusion, we suggest that preemptive
      transplantation should be applied to eligible patients.

PMID- 18089323
TI  - CD8+FOXP3+T cells from renal transplant recipients in quiescence induce
      immunoglobulin-like transcripts-3 and -4 on dendritic cells from their respective
      donors.
AB  - In previous studies, CD8+FOXP3+ T cells have been shown to upgrade the inhibitory
      receptors on dendritic cells (DC) in heart transplantation patients. The
      inhibitory receptor were immunoglobulin-like transcripts (ILT)-3 and ILT-4, which
      were highly expressed on tolerogenic dendritic cells. Our study focused on the
      CD8+FOXP3+ T cells from allogeneic renal transplant recipients, seeking to
      dissert their function in inducing ILT-3- and ILT-4-expressing dendritic cells.
      We analyzed 11 quiescent renal transplant recipients and their respective donors.
      Reverse transcriptase polymerase chain reaction analysis showed that the levels
      of Foxp3 mRNA in CD8+ T cells after renal transplantation were significantly
      higher than those in CD8+ T cells before transplantation. We further investigated
      the capacity of allospecific CD8+FOXP3+ T cells to induce upregulation of the
      inhibitory receptors ILT-3 and ILT-4 on DC. Data from FACS showed that CD8+FOXP3+
      T cells induced greater expression of ILT-3 and ILT-4 on DC in an allospecific
      fashion. This study confirmed that Foxp3 gene expression was enhanced among
      quiescent renal transplant patients, suggesting that CD8+FOXP3+ T cells play an
      important role in unresponsiveness related to upregulated ILT-3 and ILT-4
      receptors on DC.

PMID- 18089324
TI  - A clinicopathologic study of p27(kip1) expression in renal allograft biopsy.
AB  - BACKGROUND: P27 (Kip1) is an inhibitor of cyclin-dependent kinases/cyclin complex
      that keeps mature cells growth-arrested. In IgA nephropathy, a decreased p27kip1
      expression in podocytes has been reported to be related to lesion formation of
      focal segmental glomerulosclerosis and renal dysfunction. We reviewed the p27kip1
      expression in transplanted kidneys. METHODS: p27kip1 expression was examined
      immunohistochemically in 26 allograft biopsy specimens. RESULTS: p27kip1
      expression was recognized in podocytes. Patients with more than 0.5 g proteinuria
      showed fewer p27kip1-positive cells than those with less than 0.5 g proteinuria.
      The decreased p27kip1 expression in podocytes was related to cg and ah of the
      Banff 97 classification. In the two cases in which p27kip1 expression was
      remarkably decreased, elevation of the serum creatinine level was recognized at
      the time of biopsy, resulting in kidney transplant loss. The histological
      findings were chronic/sclerosing allograft nephropathy grade II-(b) in both
      cases. CONCLUSION: In conclusion, decreased p27kip1 expression in podocytes
      suggested a significant role in proteinuria among renal transplant recipients.

PMID- 18089325
TI  - Pregnancy-associated plasma protein-A: evaluation of a new biomarker in renal
      transplant patients.
AB  - OBJECTIVE: Trophoblasts produce high concentrations of pregnancy-associated
      plasma protein-A (PAPP-A) during pregnancy. PAPP-A has been described as a new
      inflammatory marker and an independent risk factor for posttransplant
      cardiovascular risk. This study evaluated the clinical significance of PAPP-A in
      renal transplant patients. METHODS: The study included 78 adult renal transplant
      patients (56 men and 22 women) and 37 control subjects (27 men and 10 women). We
      determined serum PAPP-A, urea, creatinine, uric acid, total cholesterol, high
      density lipoprotein cholesterol, low-density lipoprotein cholesterol,
      triglyceride, 24-hour proteinuria, and C-reactive protein (CRP) levels. RESULTS:
      The PAPP-A level was significantly higher among renal transplant patients [median
      (interquartile range), 10.5 (6.4 to 15.4) mU/L] than the control group [3.9 (3.1
      to 5.2) mU/L; P<.001]. There were significant positive correlations between serum
      PAPP-A levels and urea (r=.547, P=.001), creatinine (r=.497, P=.001), uric acid
      (r=.452, P=.001), and CRP values (r=.387, P=.001). The drugs used for
      immunosuppression in transplant patients (cyclosporine, tacrolimus, and others)
      did not significantly affect serum PAPP-A levels (P>.05). CONCLUSION: We
      concluded that PAPP-A level was elevated in renal transplant patients and that
      high levels of PAPP-A might be a prognostic marker owing to their close
      association with high serum levels of urea, creatinine, uric acid, and CRP.

PMID- 18089326
TI  - The approach by midline incision for extraperitoneal kidney transplantation.
AB  - No data are available on incisional hernia in renal transplant recipients using a
      midline incision. This study evaluated the incidence of abdominal wall incisional
      hernia, comparing two surgical approaches: midline and J-shaped incisions.
      METHODS: Between 1991 and 2005, 415 consecutive patients underwent renal
      transplantation: between 1991 and 1997, 139 patients through a lateral incision;
      between 1997 and 2005, 137 of 276 renal transplant patients via a midline
      incision, and 139 via a J-shaped incision. We evaluated the incidence of
      incisional herniae in these patients. Analyzed factor risks included: age, sex,
      body mass index, diabetes, reoperation, lymphocele, dialysis time, underlying
      renal disease, and immunosuppressive therapy. RESULTS: During follow-up, 15
      patients of 415 transplantations were dead or lost to follow-up. Incisional
      herniae were identified in 12 cases of 132 (9%) between 1991 and 1997. Between
      1997 and 2005 we identified 3 of 133 (2.2%) patients who underwent a midline
      incision and 15 of 135 (11.1%) who received a J-shaped incision (P=.005).
      Comparing midline and J-shaped incisions before and after 1997, the incidence
      reduction was significant (P=.01). Comparing the incidence among patients treated
      with J-shaped incision before versus after 1997, the increased incidence was
      insignificant (P=.6). Multivariate analysis found the most important risk factor
      was obesity followed by polycystic kidney disease, reoperation, wound infection,
      and mycophenolate mofetil therapy. CONCLUSIONS: Our data showed an advantage of a
      midline incision. Strategies to prevent surgical complications, such as abdominal
      wall relaxation and poor cosmetic results, are needed; the midline incision may
      be a possible alternative to address this complication.

PMID- 18089327
TI  - Adherence to immunosuppression: a prospective diary study.
AB  - Immunosuppression adherence among kidney transplant recipients is essential for
      graft survival. However, nonadherence is common, jeopardizing graft survival.
      Besides skipping dosages, little is known about other forms of medication
      nonadherence and their underlying reasons. This study sought to examine patients'
      extent of medication adherence over time and reasons for nonadherence. Thirty
      nine new kidney transplant recipients were asked to complete a month-long
      medication-taking diary that included reporting medication nonadherence such as
      skipped medications, medications taken early or late, taking dosages greater or
      less than prescribed, and the reason for each occurrence of nonadherence. Of the
      20 (51%) patients who completed the diary, 11 (55%) reported at least 1 form of
      nonadherence. Eleven patients reported taking their immunosuppression at least 1
      hour later than the prescribed time, 1 patient reported skipping medication, but
      no patients reported changing the dosage on their own. Immunosuppression was
      taken on average 1.5 hours after the prescribed time. Of those patients who took
      their medications late, there were on average 3.1 occasions of taking it late.
      The most common reasons for this behavior included health care-related issues,
      followed by oversleeping, being away from home, work-related barriers, and
      forgetting. The majority of kidney transplant recipients took medications later
      than prescribed during 1 month. Future research should determine the clinical
      impact on graft function of late administration of immunosuppression.
      Interventions should be designed to better assist kidney recipients with taking
      medications on time, especially when they are away from home.

PMID- 18089328
TI  - Statins benefit outcomes of renal transplant recipients on a sirolimus
      cyclosporine regimen.
AB  - BACKGROUND: Statins offer a strategy to address dyslipidemia commonly experienced
      by immunosuppressed transplant recipients. METHODS: This single-center,
      retrospective study of 325 recipients (mean posttransplant follow-up of over 6
      years; 75.0+/-26.0 months) correlated four adverse outcomes-biopsy-confirmed
      acute rejection episodes, biopsy-confirmed chronic rejection/allograft
      nephropathy, graft loss, or death-with demographic and posttreatment variables.
      Patients were treated with a combination of sirolimus (SRL), cyclosporine (CsA),
      and various durations of steroids. Statins were prescribed for 259/325 (79%)
      recipients whose serum cholesterol exceeded 240 mg/dL and discontinued when the
      creatine phosphokinase increased fivefold (3.4%) or the liver function, threefold
      (3.0%) above normal. RESULTS: Upon univariate (hazard ratio [HR] 0.16; P<.001)
      and multivariate analysis (HR 0.38; P=.02), statins were markedly protective
      against acute rejection episodes. They reduced occurrence of chronic
      nephropathy/chronic rejection (HR 0.60; P=.03 and HR 0.52; P=.01, respectively).
      Incidences of graft loss were diminished (HR 0.26; P<.001 and HR 0.49; P=.01,
      respectively). Finally, the mortality rate was decreased (HR 0.21, P=.001 and HR
      0.26, P=.01, respectively). Upon multivariate analysis, a reduced incidence of
      acute rejection was correlated with greater exposure to SRL (HR 0.78, P=.016) and
      CsA (HR 0.39; P=.006). CONCLUSIONS: This study demonstrated compelling effects of
      statins against all adverse outcomes among patients treated with SRL-based, CsA
      containing regimens. The profoundly dyslipidemic properties of SRL may explain
      these unique findings compared with previous studies on patients treated with CsA
      based regimens.

PMID- 18089329
TI  - Basiliximab versus daclizumab combined with triple immunosuppression in deceased
      donor renal graft recipients.
AB  - In this prospective, randomized, open-label, single-center study, we compared the
      efficacy and safety of two anti-interleukin-2 receptor monoclonal antibodies
      among adult recipients of at least 1 HLA-mismatched deceased donor renal grafts.
      Eligible patients were randomized to induction with either basiliximab or
      daclizumab. Both groups received cyclosporine microemulsion (CsA Neoral),
      mycophenolate mofetil, and methylprednisolone. An intent-to-treat analysis of 1
      year data assessed the incidence of acute rejection episodes, the renal graft
      function, the safety, and the patient and graft survivals. Among 127 patients,
      six (10.0%) and seven (11.5%) patients experienced biopsy-confirmed acute
      rejection at 12 months, in the basiliximab and the daclizumab groups,
      respectively. Two renal grafts were lost in the basiliximab and six in the
      daclizumab cohort, one of them due to rejection. One basiliximab and two
      daclizumab patients died. Hospital treatment was required for 25 and 33
      infections in basiliximab and daclizumab groups, respectively. One basal cell
      carcinoma of skin was detected. One hypersensitivity reaction was observed with
      daclizumab. At 12 months, serum creatinine was 101+/-28 micromol/L with
      basiliximab and 109+/-41 micromol/L with daclizumab. Patient survival was 98.4%
      with basiliximab and 96.7% with daclizumab, and graft survival was 96.8% versus
      90.8%, respectively. No significant differences were observed between the groups.
      Basiliximab or daclizumab combined with triple therapy was an efficient and safe
      immunosuppression strategy, demonstrated with low incidence of acute rejection
      episodes, an acceptable adverse event profile, excellent graft function, and high
      survival rates in adult recipients within the first year after deceased donor
      renal transplantation.

PMID- 18089330
TI  - Posttransplantation conversion to sirolimus-based immunosuppression: a single
      center experience.
AB  - Sirolimus (SRL) has become an option in kidney transplantation, especially among
      patients who develop chronic allograft nephropathy (CAN). This study sought to
      evaluate the safety and efficacy of SRL in 103 kidney recipients of mean age 40
      years, including 78 recipients of organs from deceased donors. The major reason
      for conversion was calcineurin inhibitor (CNI) nephrotoxicity (42.3%) followed by
      CAN (35.4%). A preconversion kidney biopsy was performed in 89 patients with CAN
      diagnosed in 51. Mean time to conversion was 40.5 months. The new therapy was:
      SRL/mycophenolate mofetil (MMF)/prednisone (Pred) in 79 patients; SRL/tacrolimus
      (TAC)/Pred in 15; and other SRL combinations in 9. The target SRL trough level
      was 5.0 to 8.0 ng/mL. To evaluate the impact of conversion on renal function, we
      compared the proteinuria and inverse serum creatinine at 3 months before
      conversion, at conversion, and at 1, 3, 6, 12, and 24 months postconversion. The
      overall mean follow-up time was 13.2 months. The analysis showed significant
      improvement in renal function at month 1 postconversion (P<.05) with
      stabilization thereafter. The SRL/MMF combination frequently induced anemia
      and/or leukopenia (n=23). Infections included pneumonia (n=10), herpes zoster
      (n=7), herpes simplex (n=3), cytomegalovirus (n=2), histoplasmosis (n=2),
      tuberculosis (n=2), and neurocryptococcosis (n=1). Reasons for SRL
      discontinuation were myelotoxicity (n=4), infection (n=3), nephrotoxicity (n=3),
      gastrointestinal intolerance (n=3), myopathy (n=1), pneumonitis (n=1),
      hyperlipidemia (n=1), and other reasons (n=3). Graft loss occurred in 29 patients
      due to CAN (n=21) followed by death (cardiovascular, n=2; infectious, n=2), acute
      rejection (n=3), and infection following immunosuppression withdrawal (n=1). We
      concluded that SRL represented an option but reducing associated
      immunosuppression should strongly be considered to minimize the frequent side
      effects, especially infections.

PMID- 18089331
TI  - Characterization of dendritic cell subsets in patients undergoing renal
      transplantation.
AB  - Dendritic cells (DCs) play a key role in transplantation tolerance and immune
      reactions to transplants. In order to ascertain whether DC levels are predictive
      for rejection, we examined the levels and expression patterns of DCs of renal
      transplant patients following immunosuppressive and/or surgical interventions.
      Myeloid (HLA-DR+/CD11c+) and plasmacytoid (HLA-DR+/CD123+) DCs were characterized
      by flow cytometry over 28 days. We demonstrated that myeloid DCs and plasmacytoid
      DCs in peripheral blood were discernable and dramatically decreased following
      renal transplantation and immunosuppression. Furthermore, the expression of CD62L
      was significantly up-regulated (P=.032), while CD86 was significantly down
      regulated (P=.008) on myeloid but not plasmacytoid DCs. Although DC levels alone
      were not predictive for the occurrence of a rejection episode, in combination
      with other factors they may be indicative of rejection, thereby sparing the
      patient a biopsy.

PMID- 18089332
TI  - Feasibility of C2 monitoring in Korean renal transplantation.
AB  - BACKGROUND: In spite of efforts for simplified and optimal monitoring,
      variability of cyclosporine (CsA) absorption has shown limited clinical impact.
      We performed the present study to evaluate the feasibility of C2 monitoring and
      the optimal target C2 level in Korean recipients. PATIENTS AND METHODS: Sixty
      recipients who underwent first living donor kidney transplantations between
      December 2003 and May 2005 and who were treated with a regimen of CsA,
      mycophenolate mofetil, and steroid were enrolled in this study. CsA dose was
      adjusted according to conventional trough levels. Blood samples were collected
      just before (C0) and at 1, 2, 3, 4, 6, 8, and 12 hours (C1, C2, C3, C4, C6, C8
      and C12) after dosing on days 2, 3, and 7 posttransplantation. On days 14 and 28,
      we determined C0, C1, C2, C3, and C4. We compared CsA levels between a no
      rejection versus a rejection group. RESULTS: In 8 recipients there were 1 or more
      acute rejection episodes (13.3%). C2 levels correlated closely with AUC0-4 on
      each day (r=.892-.944, P<.01), but C2 levels were not significantly different
      between the no rejection and the rejection group (P>.05). Mean C2 level on days 3
      to 28 was significantly different between the 2 groups. (P=.045). One recipient
      (5.3%) with a mean C2 level greater than 1000 ng/mL underwent acute rejection.
      CONCLUSIONS: CsA concentration monitored as mean C2 levels early
      posttransplantation rather than a single point concentration on a single day was
      a predictor of acute rejection in kidney transplantation. Within the first month
      posttransplantation, the target C2 level is recommended to be over 1000 ng/mL for
      Korean recipients.

PMID- 18089333
TI  - Cyclosporine monitoring in peripheral blood mononuclear cells: feasibility and
      interest. A prospective study on 20 renal transplant recipients.
AB  - Cyclosporine (CsA) has potent immunosuppressive properties, reflecting its
      ability to block the transcription of cytokine genes (mainly interleukin 2) in
      CD4+ T lymphocytes, markedly improving transplantation outcomes in the past 20
      years. CsA pharmacokinetic variability and renal toxicity require whole blood
      (WB) monitoring by 4-hour area under the drug concentration curves (AUC0-4) or 2
      hour postdose concentration (C2) monitoring. Nevertheless, graft rejection can
      occur despite target blood levels, suggesting that WB monitoring does not
      guarantee optimal immunosuppression. For a decade, pharmacologists and clinicians
      have worked to optimize CsA doses; some authors, inspired by its mechanism of
      action, have proposed therapeutic drug monitoring using peripheral blood
      mononuclear cells (PBMC; lymphocytes and monocytes). The aim of this study was to
      assess the feasibility and interest of CsA monitoring in PBMC ([CsA]PBMC). We
      also measured in vitro distribution of CsA in CD4+ and CD4- subsets.

PMID- 18089335
TI  - Efficacy and safety of caspofungin in solid organ transplant recipients.
AB  - Efficacy and safety data for the echinocandins in solid organ transplant (SOT)
      recipients are limited. We reviewed data from three clinical trials that enrolled
      SOT patients receiving caspofungin therapy for an invasive fungal infection
      (IFI). Caspofungin was administered at doses ranging from 50 to 100 mg/day.
      Efficacy was assessed in all patients at the end of caspofungin therapy (EOT).
      Adverse events (AE) and laboratory data were collected from all patients. We
      identified data from 22 SOT patients (aged 34-67 years) with proven invasive
      candidiasis (IC; 6 patients) or proven or probable invasive aspergillosis (IA; 16
      patients) who received at least one dose of caspofungin therapy. All patients
      with IC received caspofungin as primary therapy. Caspofungin success against IC
      at EOT was 83% (5 of 6), with responses seen across Candida spp. Success by SOT
      type was: kidney 4 of 5 and liver 1 of 1. All 16 patients with IA (all pulmonary)
      received caspofungin as salvage therapy. Caspofungin success against IA at EOT
      was 50% (8 of 16), with responses seen for both definite (3 of 4) and probable IA
      (5 of 12). Success by SOT type was: heart 2 of 2, heart/lung 0 of 2, kidney 3 of
      3, liver 1 of 3, and lung 2 of 6. The outcome was not influenced by caspofungin
      dose. Caspofungin, dosed for 2 to 162 (mean 36.8) days, was well tolerated. No
      patient had a serious drug-related adverse event or discontinued caspofungin due
      to toxicity. Based on these limited data, caspofungin appears to be an effective
      and well-tolerated option for the treatment of IC and IA in SOT recipients.

PMID- 18089334
TI  - Establishing pharmacokinetic bioequivalence of valganciclovir oral solution
      versus the tablet formulation.
AB  - Dosing with valganciclovir tablets may not be appropriate in some patients, such
      as those on hemodialysis or children. A "tutti-frutti" flavored oral
      valganciclovir solution has been developed to provide flexibility in dosage
      needed to accommodate these patients. An adult, multicenter, open-label
      randomized trial was conducted to establish bioequivalence between valganciclovir
      oral solution and valganciclovir tablets. Pharmacokinetic profiles and safety of
      the oral solution versus the tablet formulation were determined in 23 renal
      transplant recipients with estimated creatinine clearance>or=60 mL/min who had
      been receiving cytomegalovirus prophylaxis with valganciclovir for >or=4 days
      prior to the administration of the study drug. Patients received two doses of 900
      mg valganciclovir either by tablet or oral solution in random order once daily
      over 6 days. Plasma concentrations of ganciclovir were assessed on days 2, 4, and
      6 predose and at 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, and 12 hours after
      the dose. Maximum mean plasma concentrations (Cmax) were 6.73 microg/mL and 6.39
      microg/mL for the valganciclovir tablet and oral solution, respectively, with
      identical mean AUC0-24 of 51.2 microg.h/mL. For both the AUC0-24 and Cmax ratio,
      the 90% Cl of the mean ratios of the oral solution relative to the tablet
      formulation lies within the acceptance region (80% to 125%) required by the US
      Food and Drug Administration and European Agency for the Evaluation of Medicinal
      Products. With the demonstration of bioequivalence and no differences in the
      incidence of adverse effects, it will be possible to interchangeably use the oral
      formulation.

PMID- 18089336
TI  - The incidence and clinical outcome of YMDD mutants in hepatitis B surface antigen
      positive renal allograft recipients after prolonged lamivudine therapy.
AB  - Although lamivudine (LAM) is a potent inhibitor of hepatitis B virus (HBV),
      prolonged therapy may induce the development of LAM-resistant strains, YMDD
      mutants. Although YMDD mutants have impaired replication that leads to a benign
      clinical course compared with wild-type virus, some immunosuppressive agents may
      enhance replication of YMDD mutants, causing a severe hepatitis flare. We
      retrospectively investigated the incidence and clinical outcomes of YMDD mutants
      in renal allograft recipients on immunosuppressive treatment. Clinical records of
      25 renal allograft recipients, who underwent renal transplantation between
      December 1997 and February 2006 were hepatitis B surface antigen positive at the
      time of transplantation, were reviewed. All patients received LAM treatment after
      renal transplantation. Over 9 to 98 months of follow-up, 16 patients (64.0%)
      maintained undetectable HBV DNA levels; however, 9 patients (36.0%) showed
      persistent or increased levels of HBV DNA. Seven were identified as having
      developed YMDD mutants. Although genotypic analysis was not performed, YMDD
      mutants were strongly suspected in another two patients, who developed severe
      hepatic dysfunction combined with high levels of HBV viremia at close to 2 years
      of LAM therapy. One patient recovered after hepatic transplantation and another
      patient died of hepatic failure. In conclusion, the incidence of YMDD mutants was
      similar to that of nonimmunosuppressed individuals; however, the presence of
      these mutants made it more likely for severe liver disease to develop in renal
      transplant recipients. Therefore, close monitoring for the development of YMDD
      mutants should be performed during LAM treatment, especially in this group of
      patients.

PMID- 18089337
TI  - Hepatitis C virus infection and outcome of renal transplantation.
AB  - Chronic hepatitis B and C viruses (HBV and HCV) are common problems in renal
      transplant patients. There is no uniform agreement regarding their influence on
      graft outcomes and patient survival. We evaluated the influence of anti-HCV and
      hepatitis B surface antigen-positive status; gender; age>49 years at the time of
      transplantation; alanine aminotransferase elevation; acute rejection; type of
      graft; number of transplants; and maintenance/induction immunosuppressive
      treatment on both graft and patient survivals among a population transplanted in
      our center between 1991 and 2004. Univariate analysis showed that anti-HCV
      positive status, three-drug immunosuppressive therapy, and one or more episodes
      of acute rejection were associated with diminished graft survival. Over the age
      of 49 years at the time of transplantation, anti-HCV-positive status, cadaveric
      donor, kidney-pancreas transplantation, and three-drug immunosuppressive therapy
      were associated with diminished patient survival. Upon multivariate analysis,
      reduced patient survival was associated with the same variables as in the
      univariate analysis: anti-HCV-positive status, three-drug immunosuppressive
      therapy, and one or more episodes of acute rejection were associated with
      diminished graft survival. In our experience, anti-HCV-positive compared with
      anti-HCV-negative status was associated with a reduced graft (56% vs. 75%;
      P=.0002) and patient survival (68% vs. 83%; P=.0028).

PMID- 18089338
TI  - Urinary tract infections following renal transplantation: a single-center
      experience.
AB  - BACKGROUND: Although infectious complications are the second most common cause of
      death after transplantation, there appears to be insufficient data regarding the
      impact of urinary tract infections (UTIs) on graft outcome and patient mortality
      and morbidity. In this study, we evaluated the incidence, risk factors, and long
      term effects of UTIs on graft function. METHOD: We performed a retrospective
      cohort study reviewing the medical records of patients who received a renal
      transplant at our center from January 1999 to December 2006. All UTIs, risk
      factors, long-term graft function, graft loss, and death were recorded. Outcomes
      among patients with UTIs were compared with those without UTIs. RESULTS: Fifty
      six of 136 patients (41.2%) had at least one UTI over a mean period of 38+/-25
      months after transplantation. While there was a tendency toward graft loss among
      patients with UTIs (16.1% vs 6.3%, P=.08), there was no increased risk of death.
      The patients with UTIs displayed higher serum creatinine levels (1.7+/-1.4 vs
      2.3+/-2.5 mg/dL, P=.07) compared to non-UTI patients in the long term. Upon
      multivariate analysis, female gender was the only risk factor for posttransplant
      UTIs. We did not determine any immunosuppressive drug as a risk factor for UTIs.
      The most frequent pathogens isolated in urine culture were Escherichia coli
      (n=72, 59.1%) and Klebsiella spp (n=21, 16.9%), and there were eight cases of
      bacteremia. CONCLUSION: UTIs are a frequent problem after kidney transplantation.
      Female recipients are at greatest risk. In the long-term, UTIs should be
      considered as a potential risk for poorer graft outcomes.

PMID- 18089339
TI  - Predictors of renal function improvement following tacrolimus conversion in
      cyclosporine-treated kidney transplant recipients.
AB  - The objective of this study was to evaluate the relationship between variability
      of cyclosporine (CsA) absorption and tacrolimus (TAC) conversion seeking factors
      that predict improvement in allograft function after TAC conversion. We performed
      a retrospective study of 44 adult kidney transplant recipients undergoing
      conversion from CsA to TAC-based immunosuppression. Before TAC conversion,
      patients had complete, consecutive, 6 monthly C2 levels and a follow-up duration
      beyond 6 months after TAC conversion. The patients were divided into 2 groups:
      one (n=23) with low variability of CsA absorption and one (n=21) with high
      variability of CsA absorption. At TAC conversion, the estimated glomerular
      filtration rate (eGFR) was similar in both patient groups. Six months after TAC
      conversion, eGFR improved in both groups. Stepwise regression analysis revealed
      the DeltaSCr6 (change in serum creatinine level at 6 months) to be independently
      associated with the preconversion serum creatinine (SCr; P<.0001) and the percent
      coefficient of variation (%CV) of SCr (P=.0034). DeltaSCr6 was inversely
      associated with posttransplantation years (P=.0033), and 6-month TAC blood levels
      (P=.0053). The DeltaSCr6 was not associated with variability of oral CsA
      absorption. The cutoff value of baseline SCr at TAC conversion differentiated an
      increase in or reduction of SCr to be about 1.0 mg/dL. Our study of CsA-treated
      kidney transplant recipients who underwent TAC conversion showed that a
      preconversion SCr>1.0 mg/dL, a high variability of SCr, and early TAC conversion
      predicted greater short-term benefit on graft function.

PMID- 18089340
TI  - Acute effects of a single dose of phosphodiesterase type 5 inhibitor (sildenafil)
      on systemic arterial blood pressure during exercise and 24-hour ambulatory blood
      pressure monitoring in heart transplant recipients.
AB  - BACKGROUND: Arterial systemic hypertension (SH) can be associated with a decrease
      in endothelium-dependent nitric oxide (NO). Sildenafil increases cyclic guanosine
      monophosphate (cGMP), a mediator of NO. However, little is known about the
      effects of PDE5 inhibition on 24-hour ambulatory pressure (ABP) and exercise
      blood pressure, noreprinephrine (Nor), and exercise capacity, especially after
      orthotopic heart transplantation (OHT). METHODS: We studied 22 OHT patients who
      on the 1st day underwent a cardiopulmonary (CP) self-controlled treadmill 6' walk
      test (6') and, then, an ECG monitored CP treadmill maximal exercise test (Ex)
      within 60 and 90 minutes after oral Sildenafil (Sil; 50 mg) or placebo (Pl) given
      at random, and ABP. We determined at basal position (b), in the last minute of
      the 6' and at the peak Ex, the HR (bpm), Systolic blood pressure (SBP), and
      diastolic blood pressure (DBP), (mm Hg), VO2 (mL/kg/min), Slope VE/VCO2, exercise
      time (ET, min), distance (D; miles), and Nor (pg/mL). Also, after CP tests, 24-h
      SBP and DBP, the measurements were repeated on the 2nd day when the cross-over
      was done. RESULTS: Sil significantly reduced blood pressure in the basal position
      and during exercise. It also promoted a significant reduction in SBP and DBP
      during 24 hours, daytime and nighttime. Sil did not change exercise capacity.
      CONCLUSION: The NO-cGMP pathway seems to play a role in blood pressure control in
      OHT. In addition to antihypertensive therapy, PDE5 inhibition may have potential
      beneficial effects on hypertensive OHT.

PMID- 18089341
TI  - Reduction of proteinuria during intensified antihypertensive therapy in children
      after renal transplantation.
AB  - BACKGROUND: Proteinuria together with hypertension are known risk factors for
      poor allograft as well as patient survivals after renal transplantation. In
      adults, proteinuria can be reduced by lowering blood pressure and by using
      angiotensin-converting enzyme inhibitors. In children, no study has investigated
      the antiproteinuric effects of antihypertensive therapy. Herein we investigated
      changes in proteinuria among a subgroup of children with proteinuria>or=200
      mg/m2d in an interventional study primary aimed to improve the efficacy of
      antihypertensive therapy. PATIENTS AND METHODS: Twelve children with
      proteinuria>or=200 mg/m2d were included in the study. Proteinuria was
      investigated at baseline and at 1 year after changes in antihypertensive therapy.
      Blood pressure (BP) was measured using ambulatory BP monitoring. RESULTS: The
      median protein excretion of 226 mg/m2/d (range, 41-1478 mg/m2/d) at 1 year before
      the study did not change significantly at study baseline (278 mg/m2/d; range, 205
      1264 mg/m2/d), but decreased significantly to 199 mg/m2/d (range, 65-749 mg/m2/d)
      after 1 year (P<.05 vs baseline). The number of antihypertensive drugs was
      increased from 1.6+/-1.0 to 2.2+/-0.9 drugs/patient after 1 year (P<.05). The use
      of different classes of antihypertensive drugs did not change significantly. Mean
      ambulatory systolic and diastolic BP at daytime and diastolic BP at nighttime did
      not change significantly after 1 year; mean ambulatory systolic BP at night
      decreased from 1.60+/-1.54 to 1.04+/-0.97 standard deviation score (P<.05). Graft
      function did not change significantly. CONCLUSION: We demonstrated that
      proteinuria among children after renal transplantation was reduced by intensified
      antihypertensive therapy using all classes of antihypertensive drugs.

PMID- 18089342
TI  - Renal osteodystrophy after successful renal transplantation: a histomorphometric
      analysis in 57 patients.
AB  - Renal transplantation is the treatment of choice for patients with end-stage
      renal disease. It corrects most of the metabolic abnormalities that cause renal
      osteodystrophy. Nevertheless, renal osteodystrophy persists in many transplant
      recipients. The aim of this study was to investigate frequency and
      histomorphometric pattern of bone disease after renal transplantation. Bone
      biopsy specimens were taken from the iliac crest of 57 patients, including 28
      women (26-70 years old) and 29 men (27-67 years old). Indications for biopsy were
      hypercalcemia, elevation of parathyroid hormone, and, in 19 cases, without
      suspected bone abnormalities based on laboratory parameters. The mean time of
      dialysis prior to renal transplantation was 43 months (range, 6-91 months in
      women and 10-111 months in men) and the mean interval between transplantation and
      bone biopsy was 53.5 months (range, 4-191 months in women and 5-90 months in
      men). Fourteen patients were treated with either 25-hydroxyvitamin D3 and/or 1
      alpha hydroxyvitamin D3 or 1,25 dihydroxyvitamin D3, 3 with phosphate-binding
      agents. The immunosuppression consisted of cyclosporine, azathioprine, and
      prednisolone. The cumulative dosage of corticosteroids was 5569+/-5305 mg. For
      static and dynamic histomorphometry, we used American Society of Bone and Mineral
      Research nomenclature. Mild osteitis fibrosa and osteitis fibrosa, the most
      frequent forms of renal osteodystrophy, were observed in 13. (22.8%) and 14
      patients (24.6%), respectively. Mixed uremic osteodystrophy was found in 7
      patients (12.3%), adynamic renal bone disease in 3 patients (5.3%), and
      osteomalacia in 2 patients (3.5%). In 13 patients (22.8%), reduced bone mass and
      structural damage without typical signs of renal osteodystrophy, such as
      endosteal fibrosis or osteoclasia, were detected, and 5 patients (8.7%) showed
      normal histomorphometric parameters. We concluded that renal osteodystrophy,
      especially forms with high bone turnover, persisted in many patients after
      successful renal transplantation. This finding may be due to preexisting
      conditions, such as duration of dialysis and degree of hyperparathyroidism. Bone
      disease is increased by corticosteroid and immunosuppressive therapy after renal
      transplantation and requires close monitoring.

PMID- 18089343
TI  - Noninvasive assessment of left ventricular function prior to and 6 months after
      renal transplantation.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of a successful
      kidney transplantation on left ventricular functional parameters that can be
      measured with gated-single photon emission computed tomography (gated-SPECT)
      myocardial perfusion scintigraphy in patients with end-stage renal disease.
      MATERIALS AND METHODS: Thirty-two consecutive patients (22 male) who had
      undergone a successful kidney transplantation in whom gated-SPECT myocardial
      perfusion scintigraphy was performed prior to and 6 months after surgery were
      included. Functional parameters, such as left ventricular ejection fraction
      (LVEF), wall motion, and wall thickening, were calculated with quantitative gated
      SPECT. RESULTS: The mean LVEF improved significantly (P<.001) from 52% (SD+/-11)
      before to 63% (SD+/-10) after renal transplantation. This was attributable to a
      significant improvement in the end-systolic volume (P=.028). Wall motion and wall
      thickening improved in almost all myocardial segments. We found a significant
      correlation between the levels of urea and creatinine and the LVEF. However,
      correlations between an increase in the LVEF and the improvement in urea (P=.30)
      and creatinine (P=.26) levels were not significant, which is probably related to
      the number of patients studied. CONCLUSION: The systolic left ventricular
      dysfunction in terms of LVEF, wall motion, and wall thickening improves
      significantly 6 months after kidney transplantation in patients with end-stage
      kidney disease. Long-term follow-up is required to establish the prognostic value
      of these findings.

PMID- 18089344
TI  - Effect of folate, vitamin B6, and vitamin B12 intake and MTHFR C677T polymorphism
      on homocysteine concentrations of renal transplant recipients.
AB  - Plasma hyperhomocysteinemia (HHcy) is considered a risk factor for chronic
      allograft dysfunction (CAD), the main cause of functional loss in transplant
      recipients. Genetic polymorphisms that alter enzymes involved in homocysteine
      (Hcy) metabolism, such as methylenetetrahydrofolate reductase (MTHFR), and
      vitamin deficiency can result in HHcy. The objectives of this study were to
      investigate the relationship between HHcy and CAD development, and to evaluate
      the effect of intake of folate and vitamins B6 and B12 as well as MTHFR C677T
      polymorphism on Hcy concentrations. Ninety-eight renal transplant recipients
      including 48 showing CAD and 50 with normal renal function (NRF), were included
      in this cross-sectional study. Peripheral blood samples were collected for plasma
      Hcy quantification by liquid chromatography/sequential mass spectrometry (LC
      MS/MS), and for MTHFR polymorphism analysis using polymerase chain reaction
      restriction fragment length polymorphism. Dietary intake was evaluated using a
      nutritional questionnaire. HHcy (P=.002) and higher mean concentrations of Hcy
      (P=.029) were associated with CAD. An association was observed between HHcy and
      677T variant allele in the CAD group (P=.0005). There was no correlation between
      Hcy concentration and folate, vitamin B6 or vitamin B12 intake in the CAD group.
      However, a negative correlation was observed between Hcy concentration and folate
      intake (P=.043), and also between Hcy concentration and vitamin B6 intake
      (P=.030) in the NRF group. According to our study, HHcy is associated with CAD
      development. In patients with CAD, MTHFR polymorphism seems to have a greater
      effect on the Hcy concentration than the vitamin intake. Increased folate and
      vitamin B6 intakes seem to reduce Hcy concentrations among transplant recipients
      with NRF, and could contribute to reducing the risk of CAD development.

PMID- 18089345
TI  - Overview of the MELD score and the UNOS adult liver allocation system.
AB  - On February 27, 2002, the United Network for Organ Sharing (UNOS) introduced a
      new allocation policy for cadaveric liver transplants, based on the Model for End
      Stage Liver Disease (MELD) score. This new policy stratifies the patients based
      on their risk of death while on the waiting list. We analyzed the background and
      main features of this new allocation policy to evaluate the effects on waiting
      list dynamics as well as the accuracy of MELD as a predictor of
      pretransplantation mortality and posttransplantation outcome. MELD has proved to
      be accurate as a predictor of waiting list mortality, but seems to be less
      accurate to predict posttransplantation outcome. Immediate effects of the new
      policy were a reduction in the waiting list, while organs were primarily directed
      to sicker patients with reduced waiting times. There was a statistically but not
      significantly reduced number of patients removed from the list due to death or
      severity of sickness. The balance between medical urgency and transplant benefit
      is still to be defined as is the relationship between pretransplantation criteria
      and posttransplantation outcomes, and the way this relationship should be
      included in the allocation policy.

PMID- 18089346
TI  - Comparison of Child-Turcotte-Pugh and pediatric end-stage liver disease scoring
      systems to predict morbidity and mortality of children awaiting liver
      transplantation.
AB  - BACKGROUND: The pediatric end-stage liver disease (PELD) scoring system has been
      used widely for prioritizing children awaiting orthotopic liver transplantation
      (OLT). The aim of the present study was to compare the Child-Turcotte-Pugh
      scoring system with PELD to predict morbidity and mortality of children scheduled
      for OLT before the organ was available. MATERIALS AND METHODS: From 1999 to 2006,
      83 infants and children were evaluated and scheduled for OLT. Child and PELD
      scores were determined according to the initial assessment at the time of
      listing. Outcome was examined using records and follow-up data. RESULTS: Among 83
      patients, 12% were Child A; 53%, Child B; and 35%, Child C. The mean PELD score
      at listing was 19.8+/-12.8. Patients with Child scores A, B, and C displayed mean
      PELD scores of 7.1+/-4.9, 15.7+/-9.3, and 30.5+/-11.7, respectively. Child
      classification and scoring showed a positive correlation with the PELD score
      (Spearman's correlation coefficient: 0.666, P=.001). A higher PELD score was
      associated with greater morbidity and mortality. CONCLUSION: Child classification
      has several shortcomings; therefore, PELD scores appear to be the best metric to
      prioritize children listed for OLT.

PMID- 18089347
TI  - Liver transplantation for acute liver failure: trying to define when
      transplantation is futile.
AB  - BACKGROUND: Recently, the model of end-stage liver disease (MELD) index has been
      used to select patients with acute liver failure (ALF) or transplantation. By the
      time the indication for orthotopic liver transplantation (OLT) is defined, the
      patient's clinical status may worsen. OBJECTIVE: In this study, MELD was used to
      define patients beyond OLT. METHODS: Among adult patients ALF was responsible for
      17 OLT. Their medical records were reviewed to calculate the MELD score just
      before the OLT. MELD of the deceased patients after OLT (group 1, n=8), was
      compared with the MELD score of living recipients (group 2, n=9). Creatinine
      level, need for dialysis, use of vasoactive amines, and mechanical ventilation
      before OLT were also analyzed in these groups. A significant difference was
      defined when P<.05. RESULTS: The mean MELD score+/-SD was 51.86+/-12.3 for group
      1, and 38.47+/-7.1 for group 2 (P=.02). There was no difference between the
      creatinine values for patients in the 2 groups (P=.20). Also, the use of
      vasoactive amines or the need of dialysis before OLT were not different (P=.12
      and P=.25, respectively). Group 1 was more frequently under mechanical
      ventilation, and showed a 4.29 relative risk for death after OLT. CONCLUSION:
      MELD score could be useful to define the prognosis of OLT among patients with
      ALF.

PMID- 18089348
TI  - Elevation of intact parathyroid hormone level is a risk factor for low bone
      mineral density in pretransplant patients with liver diseases.
AB  - The purpose of this study was to investigate the frequency and risk factors for
      low bone mineral density (BMD) among patients awaiting liver transplantation. BMD
      of the lumbar spine (LS) and femoral neck (FN), measured by dual-energy X-ray
      absorptiometery (DEXA), were obtained in 64 pretransplant patients. We measured
      markers of bone metabolism including serum calcium, phosphorus, serum 25
      hydroxyvitamin D (25-OH D), intact parathyroid hormone (iPTH), bone alkaline
      phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline/creatinine
      (DPD/Cr) ratio. Osteoporosis and osteopenia (low BMD) were observed in 36
      patients (36/64, 56.2%), including 6 cases of osteoporosis (6/64, 9.3%) and 30
      cases of osteopenia (30/64, 46.9%). Of all variables, cholestatic liver disease
      and elevated levels of iPTH were significantly associated with low BMD. Moreover,
      elevated iPTH level was identified as an independent risk factor for low BMD
      (P<.05, OR=1.017, 95% CI=1.001-1.032) by multivariate analysis. The median level
      of iPTH was increased to 55.6 pg/mL (range, 7.8-337 pg/mL) in the low BMD group,
      while the median level was 33 pg/mL (range, 3-162 pg/mL) in the normal BMD group
      (P<.05). This study revealed a high incidence of low BMD in the pretransplant
      patients with liver diseases. The elevated iPTH level was the predominant risk
      factor for low BMD. We suggest that both BMD and iPTH examinations be considered
      routine tests to identify the status of bone mass and bone metabolism among
      recipients prior to liver transplantation.

PMID- 18089349
TI  - Good and bad prognosis of alpha-1-antitrypsin deficiency in children: when to
      list for liver transplantation.
AB  - Alpha1-antitrypsin deficiency (alpha1-ATD) is a genetic disorder that may
      predispose to chronic liver disease. The clinical manifestations and prognosis of
      this disorder are variable. The aim of the study was to evaluate the clinical
      presentation and liver tests in two groups of children with alpha1-ATD: those
      with a good prognosis who survived long term with their native liver, and those
      with a bad one, requiring liver transplantation (OLT) or dying before OLT. We
      studied 59 children homozygous for alpha1-ATD admitted to our hospital with
      cholestasis or chronic hepatitis since infancy. Patients without liver
      transplantation were regarded to be the good prognosis group I (n=45). In
      contrast the 11 children who required liver transplantation and the three who
      died before OLT were the bad prognosis cohort (Group II, n=14). We analyzed the
      laboratory parameters of cholestasis, hepatitis, and liver insufficiency in both
      groups. In the group with a good prognosis, eight children still suffered from
      cholestasis at the ages of 9 to 14 years while nine had hepatitis at the ages of
      9 to 14 years. We observed a temporarily increased international normalized ratio
      (1.2 to 1.5) in eight subjects at the ages of 1 month to 17 years, and slight
      hypoalbuminemia (30 to 35 mg/dL) in nine children at the ages of 1 month to 10
      years. OLT was performed in 11 children at the ages of 10 to 17 years. Our
      center's experience suggested that in the PiZZ patients with portal hypertension,
      esophageal varices, or deterioration of hepatic function, liver transplantation
      should not be delayed.

PMID- 18089350
TI  - Impact of live donor age (>or=50) on liver transplantation.
AB  - BACKGROUND: The question of whether donor age negatively impacts recipient
      outcome in adult-to-adult living donor liver transplantation (LDLT) is rarely
      discussed. The aim of this study was to evaluate the impact of older donor age
      (50 years or older) on recipient outcomes in adult-to-adult LDLT. METHODS: LDLT
      data were retrospectively evaluated from our 299 LDLT cases in 297 recipients,
      which were divided into 2 groups: a younger group (group Y, donor age<50, n=237)
      and an older group (Group O, donor age>or=50, n=62). Clinical parameters of both
      recipients and donors were comparable between groups. RESULTS: There was no
      difference between the groups in patient survival or postoperative complications
      of either donors or recipients. In recipients, graft regeneration was
      significantly impaired in Group O. Graft function, including protein synthesis
      and cholestasis, was comparable between the 2 groups. CONCLUSION: Although the
      regeneration capacity of aged grafts was impaired, the function of grafts from
      older donors was comparable to that of those from younger donors. There was no
      difference in the clinical outcomes between the groups.

PMID- 18089351
TI  - Splenic embolization in liver transplant recipients: early outcomes.
AB  - Clinical improvement has been reported following splenic embolization for a wide
      variety of indications. Improvement following splenic embolization has been
      described in cirrhotic patients awaiting hepatic transplantation who are not
      candidates for surgical splenectomy. Occasionally, patients who have undergone
      hepatic transplantation have conditions that may also benefit from nonsurgical
      intervention with splenic embolization. Indications include persistent
      hypersplenism and pancytopenia precluding optimal treatment with antiviral
      therapy or chemotherapy, risk for persistent gastroesophageal variceal
      hemorrhage, and splenic artery steal syndrome attenuating hepatic arterial
      perfusion. Limited data is available on the outcome of splenic embolization in
      liver transplant recipients. We present the early outcomes of liver transplant
      recipients who were treated with splenic embolization. A retrospective chart
      review of all liver transplant recipients who underwent splenic embolization
      between 1997 and 2006 was performed, under minimal-risk study approval by the
      institutional review board. Five liver transplant recipients received splenic
      embolization: 3 for persistent hypersplenism, 1 for increased risk of
      gastroesophageal variceal hemorrhage, and 1 for splenic artery steal syndrome.
      The patients with hypersplenism demonstrated hematologic improvement, the patient
      with gastroesophageal varices did not experience any hemorrhage on follow-up, and
      the patient with splenic artery steal experienced resolution of the steal
      phenomenon. Postembolization syndrome was observed but no splenic abscess or
      death occurred. Mean follow-up was 20.2 months. In conclusion, splenic
      embolization is a safe and effective nonsurgical alternative for a variety of
      indications in liver transplant recipients.

PMID- 18089352
TI  - Spleen size changes in pediatric liver transplant recipients with functioning
      grafts.
AB  - OBJECTIVE: Hypersplenism and splenomegaly are common pathologic conditions in
      patients with chronic liver failure. Herein we discuss the prognosis of these
      conditions after orthotopic liver transplantation (OLT) in pediatric patients
      with functional grafts. MATERIALS AND METHODS: Forty-eight pediatric patients
      with cirrhosis underwent OLT. Seven patients were excluded from the study because
      of death within 1 month. Patients were divided into 2 groups: group A consisted
      of patients with nonfunctioning grafts (n=9), and group B, patients with
      functioning grafts (n=32). We measured preoperative leukocytes, platelet counts,
      and spleen sizes. Postoperative measurements were performed at 1 week as well as
      at 1, 3, 6, and 12 months after grafting. Statistical analyses were performed to
      evaluate reversal of hypersplenism and splenomegaly after OLT. RESULTS: No change
      in hypersplenism and splenomegaly was seen in group A, whereas in group B, a
      statistically significant change was seen in spleen sizes with improvement in
      hypersplenism after OLT, although persistent splenomegaly was observed in 17
      patients. CONCLUSIONS: Reversal of hypersplenism and improvement of splenomegaly
      can be expected after OLT in pediatric patients with functioning grafts. Although
      the literature points to the duration of chronic liver disease as a causative
      factor for persistent splenomegaly in adults, there must be other causes, as the
      condition is seen in pediatric patients as well.

PMID- 18089353
TI  - Use of the splenic artery for arterial reconstruction in living donor liver
      transplantation.
AB  - BACKGROUND: The present study sought to evaluate the possibility of using the
      splenic artery for arterialization of a living donor liver graft. PATIENTS AND
      METHODS: In the period between August 2004 and April 2006, we performed 31 adult
      to-adult living donor liver transplantations. In 27 patients (group A), the right
      or left hepatic artery was used to arterialize the graft, whereas in the other
      four cases (group B), we used the recipient splenic artery. RESULTS: The Model
      for End-stage Liver Disease (MELD) score of the patients averaged 17 (17.2 and
      15.2 for groups A and B, respectively) ranging between 7 and 28. We did not
      observe pancreatitis, splenic infarction, or other complications related to
      ligation of the splenic artery. Two cases (6.4%) of arterial complication were
      observed, both in group A patients. CONCLUSION: The use of the splenic artery is
      a safe, practical alternative for arterial reconstruction in living donor liver
      transplantation procedures, when the hepatic artery is not adequate or in cases
      of portal hypertension with splenomegaly.

PMID- 18089354
TI  - Outcomes in adult and pediatric liver transplantation among various ethnic
      groups.
AB  - BACKGROUND: The reported patient and graft survivals among adults post-orthotopic
      liver transplantation (OLT) are variable, with an apparent discrepancy between
      ethnic groups. The aim of this study was to evaluate the impact of ethnicity on
      patient and graft survivals among adult and pediatric patients. METHODS: A
      retrospective analysis from the UNOS/OPTN databank between January 1995 and
      December 2006 was performed on adult and pediatric liver transplant recipients.
      Patients were divided into 4 groups based on ethnicity: African Americans,
      Hispanic, Caucasians, and other. Kaplan-Meier (KM) analysis was used to calculate
      patient and graft survival. Log-rank tests were used to compare survival rates
      between groups. RESULTS: In our study 42,710 OLT patients were included in the
      analysis, 90% of whom were adults. Of the 38,639 adult recipients, 29,432 (76.1%)
      were Caucasian, 4369 (11.3%) were Hispanic, 2963 (7.7%) were African American,
      and the remaining 1875 (4.9%) were of other ethnicities. KM estimates and Cox
      regression analyses demonstrated that there was a significant ethnic difference
      in both patient and graft survivals at 1, 3, 5, and 10 years. African Americans
      showed a lower rate (P<.001). Of the 4341 pediatric recipients, 2461 (56.7%) were
      Caucasian, 797 (18.4%) were Hispanic, 824 (18.9%) were African American, and the
      remaining 259 (5.9%) were of other ethnicities. Unlike the adults, there were no
      significant differences among ethnic groups in terms of patient (P=.31) and graft
      (P=.33) survival at 1, 3, 5, and 10 years after OLT. CONCLUSION: These results
      showed that adult African American OLT patients have a reduced transplantation
      rate and a worse survival rate when compared with other ethnicities in the adult
      but not in the pediatric population. This information suggests that further
      studies are indicated to identify the causes of racial differences in transplant
      access and outcomes in the adult patient population.

PMID- 18089356
TI  - The impact of maintaining normal serum albumin level following living related
      liver transplantation: does serum albumin level affect the course? A pilot study.
AB  - Hypoalbuminemia in patients with end-stage liver disease persists for weeks even
      after liver transplantation. Human albumin is widely used for volume replacement,
      to increase oncotic pressure, to improve organ function, and to promote wound
      healing. However, these practices are not evidence-based. We prospectively
      studied the clinical outcome of 40 patients following living related liver
      transplantation. Patients were randomized to an albumin group (n=20), where 20%
      human albumin was administered to maintain serum albumin level>or=3 g/dL, and a
      control group (n=20), where there was no correction for serum albumin.
      Hemodynamics and laboratory investigations, fluid administration, blood
      transfusion, and fluid balance were recorded during the first 5 days in the
      intensive care unit. Serum albumin level was significantly higher in the albumin
      group. Heart rate, blood pressure, central venous pressure, and cardiac output
      did not vary significantly between the groups. There was no significant
      difference in serum creatinine, creatinine clearance, bilirubin, ALT, AST,
      prothrombin time, and international normalized ratio between both groups. No
      significant difference between Tacrolimus level and dose required to maintain
      therapeutic concentration was noted between both groups. Postoperative course and
      complications did not vary significantly between both groups. In conclusion,
      postoperative albumin administration to a target serum albumin>or=3 g/dL does not
      have additional benefits for the postoperative course in patients scheduled for
      living related liver transplantation.

PMID- 18089355
TI  - Predictors of blood product use in orthotopic liver transplantation using the
      piggyback hepatectomy technique.
AB  - Orthotopic liver transplantation (OLT) has historically been associated with
      massive blood loss and hemodynamic instability related to the coexistence of
      varices, coagulopathy, thrombocytopenia, and portal hypertension. Piggyback
      hepatectomy (PGB) is a technique increasingly utilized in OLT to avoid veno
      venous bypass and vena cava clamping. This study evaluated the factors associated
      with blood loss and blood product requirement in PGB. METHODS: This study is a
      retrospective review of the anesthesia preoperative and operative notes and
      computerized lab values for all adult cadaveric liver transplants over a 42-month
      period. These data were combined with the liver transplant database for analysis.
      Approximately 98% of the transplants were performed using a standard piggyback
      approach with no use of veno-venous bypass. RESULTS: Data were included for all
      526 transplants performed during this time period. Estimated blood loss (EBL) was
      1000 cc. Median transfusion requirement was 3 units packed red blood cells, 7
      units fresh frozen plasma, and 6 units platelets. Multivariate linear regression
      demonstrated that predictors of EBL were age, MELD score, preoperative
      hemoglobin, initial fibrinogen, initial central venous pressure, and total
      anesthesia time. Predictors of PRBC useage were age, MELD score, preoperative
      hemoglobin, initial fibrinogen, and anesthesia time. Postoperatively increased
      transfusion requirement was associated with increased length of hospital stay and
      lower 90-day and 1-year graft and patient survivals. CONCLUSION: These results
      demonstrate that PGB can be safely accomplished in nearly all liver transplant
      patients without venovenous bypass or vena cava clamping and with less warm
      ischemia, which may ultimately be associated with less perioperative morbidity
      and improved outcomes.

PMID- 18089357
TI  - Effect of Lactobacillus casei DN-114001 application on the activity of fecal
      enzymes in children after liver transplantation.
AB  - Immunosuppressive and antibacterial regimens in children after liver
      transplantation create a gut microflora imbalance that can be indirectly measured
      by the activity of fecal enzymes. The aim of this study was to specify the
      influence of diet supplementation with probiotic Lactobacillus casei DN on the
      activity of beta-glucuronidase, beta-glucosidase, and urease. Twenty-five
      children after liver transplantation (13 girls, 12 boys) ages 3 to 17 years were
      enrolled in the study. Two months after bacteria application the levels of all 3
      enzymes decreased, reaching statistical significance for beta-glucuronidase and
      beta-glucosidase. Complete rebound in enzyme activity was observed months after
      the end of probiotic supplementation. We concluded that Lactobacillus casei DN
      114001 consumption decreased fecal enzyme activity, a beneficial effect limited
      to the period of bacteria intake.

PMID- 18089358
TI  - The role of toll-like receptors 2 and 4 in acute allograft rejection after liver
      transplantation.
AB  - Toll-like receptors (TLRs) are germline-encoded receptors expressed on antigen
      presenting cells (APCs) that identify a variety of microbial and endogenous
      ligands and activate the innate immune responses to the presence of danger.
      However, their role in the development of allograft rejection after liver
      transplantation remains unknown. In this study, we used flow cytometry to assess
      TLR-4 and TLR-2 expression among circulating CD14+ monocytes in 64 liver
      transplant patients and 24 healthy volunteers. We demonstrated significantly
      higher TLR-2 and TLR-4 expression on circulating monocytes among conditioned
      liver transplantation recipients with acute rejection compared with those in
      clinically stable with normal liver function. Steroid pulse therapy significantly
      reduced the expression of TLR-4 and TLR-2 on the monocytes of recipients with
      acute rejection. Based on these data, we have suggested that activation of innate
      immunity in liver transplant recipients through TLR-4 and TLR-2 contributes to
      the development of acute allograft rejection after liver transplantation. The
      reduced expression of TLR-4 and TLR-2 may be one of the mechanisms by which
      steroid pulse therapy inhibits the development of acute rejection. Estimation of
      TLR expression on APCs may be predictive of in acute rejection after liver
      transplantation.

PMID- 18089359
TI  - Survival analysis of obese patients undergoing liver transplantation.
AB  - INTRODUCTION: The influence of preoperative obesity in liver transplanted
      patients remains undetermined. OBJECTIVE: To analyze the survival of obese
      patients undergoing liver transplantation. METHODS: We calculated the body mass
      index (BMI; kg/m2) of 244 liver transplantation patients. All transplantations
      were performed from September 1991 to December 2006. The patients were divided
      according to the BMI values: nonobese (NO) patients (BMI<30) and obese (O)
      patients (BMI>30). Pre- and postoperative data were used. The following
      statistical tests were employed: Student's t test, Kaplan-Meier survival, and Cox
      Mantel tests. RESULTS: Group O was composed of 38 individuals (15.3%) with BMI of
      33.1, and the BMI of NO was 24. Group O showed an average age of 50.1 years and
      group NO, 45.5 years (P<.05). Group O postoperative creatinine was higher
      (P=.001). Both groups had similar MELD scores with an average of 17.5+/-5.9.
      According to the Child-Pugh classification, group NO included 140 (69.6%) B and
      61 (30.3%) C patients; group O, 8 (21%) B and 30 (79%) C patients. There were no
      significant differences between the groups when comparing cold and warm ischemia
      times, surgical times, intensive care stay, or blood requirements. The actuarial
      survivals after 1 and 5 years were 61.3% and 51% for group O and 68% and 47% for
      NO group (P>.05). A Cox proportional hazard analysis showed that the survival
      time in this study was related to red blood cell transfusions, recipient sodium,
      MELD score, donor sodium, and age. Recipient age was a main factor in multiple
      regression analysis for obese patients in this study. CONCLUSION: There was no
      significant difference between O and NO for the 1-year and long-term survivals,
      but older patients displayed lower survival times.

PMID- 18089360
TI  - Effective anatomic reconstruction of the middle hepatic vein in modified right
      lobe graft living donor liver transplantation.
AB  - INTRODUCTION: Adult liver transplantation using the right lobe graft without a
      middle hepatic vein (MHV; modified right lobe graft) has widely been used to
      compensate for the cadaveric organ shortage. To provide appropriate functional
      graft volume in the right lobe graft used for living donor liver transplantation
      (LDLT), successful reconstruction of the MHV is required. We have described
      herein the effectiveness of an anatomic MHV reconstruction technique with
      tailoring donor hepatectomy and uniformed MHV reconstruction for modified right
      lobe grafts. MATERIALS AND METHODS: From December 2005 to August 2006, 15 adult
      patients received modified right lobe graft LDLT using a donor hepatectomy
      technique that exposed the right side of the MHV combined with a bench procedure
      that reconstructed the modified right lobe graft into the shape of extended right
      lobe graft, and a modified piggyback anastomosis. RESULTS: A total of 42 V5/V8s
      were reconstructed with 15 newly formed MHVs. The mean estimated congestion area
      was 4.2+/-2.7% of the total graft volume on computed tomography. The mean
      pressure gradient between the reconstructed MHV and the recipient inferior vena
      cava was 2.1+/-1.6 mmHg on postoperative day (POD) 7. None of the patients
      required any procedure for an outflow problem. The patency rates of the
      reconstructed MHV and its tributaries were 100% (15/15) and 95.2% (40/42),
      respectively, at POD 30; 100% (15/15) and 73.8% (31/42) at POD 60; and 86.7%
      (13/15) and 54.8% (23/42) at POD 90. All recipients are currently alive with good
      liver function. CONCLUSION: Our procedure seems to be effective for the
      reconstruction of MHV and its tributaries, and could make modified right lobe
      graft into the anatomic figure of extended right lobe graft as well as achieve
      the physiologic advantages of an extended right lobe graft.

PMID- 18089361
TI  - Efficacy of C0 and C2 monitoring in adult liver transplant recipients treated
      with neoral, mycophenolate mofetil, and steroids.
AB  - BACKGROUND: Adjustment of induction therapy with Neoral after liver
      transplantation according to C2 levels yields a reduced incidence of rejection
      compared with C0 monitoring. A combination with mycophenolate mofetil may further
      reduce episodes of acute rejection. The purpose of this analysis was to evaluate
      the predictive value of C0 and C2 monitoring and the influence of primary
      dysfunction in liver transplant recipients receiving induction therapy with
      Neoral, mycophenolate mofetil, and steroids. PATIENTS AND METHODS: One hundred
      consecutive adult liver transplant recipients were analyzed. Neoral doses were
      solely adjusted according to C0 target levels in the first week by daily analysis
      of C0 levels. C2 levels were also measured, but results did not influence the
      decision process of daily Neoral adjustments. RESULTS: The 3-month survival rate
      for all patients was 83%. For a further analysis, 35 patients were excluded, the
      remaining 65 patients experienced 15 rejections (23.1%). Patients who did reach
      C0 target levels by days 3, 5, or 7 had rejection rates no different from those
      who did not reach C0 target levels. The patients who did reach C2 target levels
      by day 7 showed a significantly lower rejection rate compared with those who did
      not reach these levels. Comparison of rejection rates among patients with primary
      function grades I and II versus grades III and IV revealed a significant
      difference. There was no correlation between Model for End-Stage Liver Disease
      (MELD) score and acute rejection episodes. CONCLUSION: Achievement of C2 target
      levels by day 7, especially in the combination of Neoral with mycophenolate
      mofetil, led to a remarkably low acute rejection rate following liver
      transplantation.

PMID- 18089362
TI  - Oral tacrolimus bioavailability is increased after right split liver
      transplantation.
AB  - OBJECTIVE: Tacrolimus (Tac) is mainly metabolized in the liver. The aim of this
      trial was to analyze Tac bioavailability after partial liver transplantation.
      PATIENTS AND METHODS: A total of 33 patients after right split liver grafting
      (n=8 living related, LRLT; n=8 cadaver split, CS) or full-size liver
      transplantation (n=17, FS) were included in this trial. All of them received Tac
      perorally with an initial dose of 2x5 mg/d. Dose adjustment was performed
      according to the Tac trough level (T0) with an initial target T0 levels of 12 to
      15 ng/mL. RESULTS: The time to reach target T0 levels tended to be lower (P=.05)
      in the split liver groups (LRLT: 2.8+/-1.6 days; CS: 2.1+/-0.9 days; FS: 4.5+/
      3.2 days). In addition, mean Tac dose to maintain the target T0 level was
      significantly decreased (P=.01) in the split liver cohorts (LRLT: 5.8+/-1.1 mg/d;
      CS: 5.5+/-2.5 mg/d; FS: 9.8+/-3.9 mg/d). Only graft weight/standard liver volume
      ratio (r=.566, P=.02) and graft weight/body weight ratio (r=.709, P=.002) showed
      significant correlations with Tac maintenance doses in the split liver group.
      CONCLUSIONS: Peroral Tac bioavailability was significantly higher after partial
      liver transplantation using the right hepatic lobe compared with full-size
      transplants. The volume of the split liver graft highly correlated with Tac
      maintenance therapy and should be used to calculate the most appropriate initial
      posttransplantation Tac dose.

PMID- 18089363
TI  - Accuracy of multidetector computed tomographic angiography for detecting hepatic
      artery complications after liver transplantation.
AB  - AIMS: The aim of this study was to evaluate the accuracy of multidetector
      computed tomographic angiography (MDCTA) for detecting hepatic artery
      complications after liver transplantation. METHODS: Between July 2001 and
      September 2006, 212 patients underwent liver transplantation including 110 (41
      female and 69 male patients); of mean age, 24 years (range=6 months to 66 years)
      who were assessed with MDCTA. First, arterial phase images obtained after
      intravenous injection of 150 mL of contrast at a rate of 4 mL/s were acquired
      using the bolus triggering technique. Then portal and late-phase images were
      obtained. Axial and coronal maximum intensity projection (MIP) images and volume
      rendered images were produced from the axial image data. Arterial vascular
      complications were noted. Stenosis was defined as severe (>75%), moderate
      (>or=50%), or mild (<50%) according to its diameter. Twenty-nine of the 38
      individuals with hepatic artery complications detected by MDCTA had correlative
      digital subtraction angiography (DSA). Seven of 110 patients with normal hepatic
      artery and venous pathologies in MDCTA also had DSA to investigate venous
      complications. RESULTS: MDCTA showed hepatic artery complications in 38 of the
      110 patients who were assessed with this modality. DSA confirmed the MDCTA
      findings in all but 1 of the 29 patients assessed with catheter angiography.
      Fourteen of the 38 individuals also underwent percutaneous interventions and
      treatment. Fifteen patients had early hepatic artery complications, and 23 late
      hepatic artery complications. The most common early complications were thrombosis
      (66.6%) and stenosis (26.6%). The most common late complications were stenosis
      (56.5%) and thrombosis (26%). If we evaluate the early and late complications,
      the incidence of late complications was greater than that of the early
      complications (61% vs 39%). There was no statistically significant difference in
      cadaveric and living donor liver transplants for early versus late or for type of
      complications. CONCLUSIONS: MDCTA is noninvasive imaging modality that accurately
      shows a variety of vascular complications after liver transplantation. We suggest
      that if we suspect any vascular complication with Doppler ultrasound, we must
      perform MDCTA for diagnosis. If we detect severe/moderate stenosis, the patient
      must undergo DSA.

PMID- 18089364
TI  - Interventional treatment of hepatic artery stenosis after orthotopic liver
      transplantation with balloon-expandable coronary stent.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of hepatic artery
      stenting with a balloon-expandable coronary stent for the treatment of hepatic
      artery stenosis (HAS) after orthotopic liver transplantation (OLT). PATIENTS AND
      METHODS: We performed retrospective review of all 11 patients who underwent
      hepatic artery stenting after a diagnosis of HAS. RESULTS: A total of 13 balloon
      expandable coronary stents were placed into 11 patients. The technical and
      immediate success rate was 100%; all stents remained patent during follow-up. One
      patient required 2 stents due to the length of the stenotic artery. Another
      underwent a second stenting after developing restenosis proximal to the original
      stenotic site. No procedure-related complications occurred, and no surgical
      revascularization or retransplantation was required during follow-up.
      CONCLUSIONS: A balloon-expandable coronary stent can play a role in the
      management of HAS. It can be used with great safety, with immediate as well as
      longer-term success.

PMID- 18089365
TI  - The experience of biliary tract complications after liver transplantation.
AB  - AIM: To report the morbidity and mortality of patients who undergo liver
      transplantation with or without T-tube implantation after
      choledochocholedochostomy as well as to discuss management of biliary
      complications. PATIENTS AND METHODS: We performed a retrospective review of 104
      liver transplantations from August 2001 to February 2006, including 51 patients
      who underwent choledochocholedochostomy with a T-tube (group A) and 53, without a
      T-tube (group B). We compared the clinical characteristics, operative methods,
      biliary complications, morbidity, mortality, and management of complications.
      RESULTS: Between the two groups, there were no significant differences in
      clinical characteristics, including sex, age, and indication for liver
      transplantation (hepatitis B virus, hepatitis C virus, alcoholic liver cirrhosis,
      or hepatocellular carcinoma), Child-Pugh classification, Model for End-stage
      Liver Disease score, and operative macroscopic/microscopic findings.
      Additionally, there was no significant difference in biliary complications. Among
      these 104 patients, 14 (13.5%) developed biliary complications: seven anastomotic
      strictures, two intrahepatic duct strictures, two anastomotic stricture combined
      intrahepatic duct stricture, one bile leakage, one bile leakage combined with
      anastomotic stricture, and one external biliary compression. Nine patients with
      anastomotic stricture underwent endoscopy with a stent, which was successful only
      in two patients. The other six patients underwent choledochojejunostomy with
      excellent results. CONCLUSIONS: This study showed choledochocholedochostomy with
      or without a T-tube after liver transplantation did not influence the biliary
      complications. The biliary complications of anastomotic stricture after liver
      transplantation can be managed by endoscopy with a stent. If endoscopy fails,
      surgical intervention should be considered immediately.

PMID- 18089366
TI  - Alternative definition of acute kidney injury following liver transplantation:
      based on serum creatinine and cystatin C levels.
AB  - OBJECTIVE: The aim of this study was to verify the estimation and the predictive
      abilities of serum creatinine (Cr), serum cystatin C (Cys C), and related
      formulas for acute kidney injury (AKI). PATIENTS AND METHODS: Thirty patients who
      underwent cadaveric donor liver transplantation were enrolled in this prospective
      study. Glomerular filtration rate (GFR) was assessed by the 99mTc DTPA clearance
      method and estimated by Cr-predicted clearances (Cockcroft-Gault method [CG] and
      abbreviated Modification of Diet in Renal Disease equation [MDRD]) as well as by
      3 other Cys C-based formulas (Hoek, Filler, and Larsson). AKI was confirmed as
      GFR<80 mL/min/1.73 m2 in the first posttransplantation week. RESULTS: GFR was
      significantly correlated with reciprocal Cr, reciprocal Cys C, and the 5 formulas
      (P<.001 for all). The receiver operating characteristic (ROC) area of Cys C was
      larger than that of Cr (.937 vs .794, P<.05). ROC area of Hoek, or Filler or
      Larsson was also larger than that of CG or MDRD (.937, .935, .937 vs .802, .849,
      P<.05 for all). ROC analysis showed the cutoff values were 1.0 mg/dL for Cr and
      1.57 mg/L for Cys C. Hoek, Filler, and Larsson equations all underestimated AKI;
      their optimal cutoff values should be adjusted to 47, 56, and 44 mL/min/1.73 m2,
      respectively. CONCLUSION: Cys C is a better predictor of AKI than Cr. A value of
      more than 1.57 mg/L might be considered a new definition of AKI.

PMID- 18089367
TI  - Comparison of hepatitis C histological recurrence rates and patient survival
      between split and deceased donor liver transplantation.
AB  - INTRODUCTION: Controversy exists as to whether there is an increased severity or
      frequency of recurrent hepatitis C viral (HCV) infection in recipients of adult
      living donor liver transplantation (LDLT) grafts. We sought to examine the time
      to histological recurrence and survival in HCV (+) patients who underwent split
      liver transplantation (SLT), which is technically similar to what occurs in the
      LDLT procedure. METHODS: Twenty four HCV (+) adult recipients were identified
      through the UNOS database as having had SLT procedures at three centers: Mount
      Sinai Medical Center, University of Chicago, and University of California at Los
      Angeles. Of these, 17 patients with comprehensive data were matched to 32 HCV (+)
      patients who underwent whole deceased donor liver transplantation (DDLT) during
      the same time period. Outcome and time to initial HCV recurrence as documented by
      liver biopsy were assessed. Liver biopsy was performed when clinically indicated.
      RESULTS: Patients who had SLT were significantly older (P=.01). There was no
      difference in number of rejection episodes (P=.40). Fifteen of 17 SLT (88%)
      versus 24/32 DDLT (75%) patients had documented HCV recurrence by biopsy (P=.46).
      The time to median cumulative incidence of recurrence of HCV post-liver
      transplantation was 12.6 months (SLT) versus 39.8 months (DDLT) patients. There
      was no difference in survival between SLT and DDLT patients (47 vs 70 months,
      P=.62) nor in cumulative incidence of histological HCV recurrence at 1, 2, and 3
      years (P=.198, .919, and .806, respectively). CONCLUSION: There is no difference
      in the cumulative incidence of histological recurrence of HCV post-liver
      transplant or in survival between recipients of deceased donor and split liver
      transplants.

PMID- 18089368
TI  - Experience with low-dose valganciclovir prophylaxis in adult liver transplant
      recipients.
AB  - Valganciclovir (VGCV) is considered the agent of choice after organ transplant
      for cytomegalovirus (CMV) prophylaxis. The purpose of this retrospective study
      was to determine the effectiveness and safety of a low-dose regimen after liver
      transplant (OLT). Eighty-five patients who underwent OLT between August 2002 and
      August 2004 were included. All patient data for the first 12 months after
      transplant were collected. Patients received VGCV 450 mg once daily for 3 months
      posttransplant. CMV infection was based on detection of CMV virus or viral
      proteins in blood. CMV disease was defined by the presence of positive
      antigenemia/viremia and evidence of clinical symptoms and/or tissue findings.
      Patients were D+R+ (54%) and D-R+ (29%), D+R-(11%) and D-R-(6%). Overall, CMV
      infection and disease occurred in 13% (11/85). CMV infection and disease occurred
      in 7% and 6%, respectively. CMV infection and disease occurred in 44% (D+R-), 13%
      (D+R+), 4% (D-R+) patients. The mean time to onset of CMV infection and disease
      was 103 days (14 to 312 days). Overall, 82% of patients received antibody
      therapy. The most common adverse events associated with VGCV were leukopenia
      (16%), thrombocytopenia (4%), anemia (<1%), and neurotoxicity (<1%). Low-dose
      VGCV was not an effective means to prevent CMV infection in high-risk (D+R-)
      patients, especially those who received antibody induction. High-risk patients
      may require a high-dose regimen, such as 900 mg daily, and/or a longer period of
      prophylaxis, and/or reduction in the use of potent antibody treatments after
      liver transplant.

PMID- 18089369
TI  - Impact of new methicillin-resistant Staphylococcus aureus carriage
      postoperatively after living donor liver transplantation.
AB  - BACKGROUND: Preoperative carriage of methicillin-resistant Staphylococcus aureus
      (MRSA) is associated with an increased risk of MRSA infection after liver
      transplantation. It is not known, however, whether new MRSA carriage
      postoperatively also increases the risk of MRSA infection after liver
      transplantation. METHODS: We retrospectively reviewed the data from 242 adult
      patients who underwent living donor liver transplantation (LDLT) including
      microbiological and medical records from admission to 3 months after LDLT. Uni
      and multivariate analyses were performed to identify independent risk factors for
      postoperative MRSA infection among preoperative noncarriers of MRSA. RESULTS:
      Postoperative MRSA infection occurred in 18 of 219 preoperative noncarriers of
      MRSA by median postoperative day 26. Operation time of at least 16 hours and
      postoperative colonization with MRSA independently predicted postoperative MRSA
      infection. CONCLUSION: Postoperative surveillance cultures should be performed
      periodically after liver transplantation to identify high-risk candidates for
      postoperative MRSA infection, even among preoperative noncarriers of MRSA.

PMID- 18089370
TI  - Antiviral prophylaxis and recurrence of hepatocellular carcinoma following liver
      transplantation in patients with hepatitis B.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is a viable treatment option
      for patients with hepatitis B (HBV) and concomitant hepatocellular carcinoma
      (HCC). However, cancer recurrence following transplantation approaches 20%. This
      study sought to identify the clinical and pathological factors associated with
      post-OLT survival. METHODS: Univariate and multivariate analyses considered the
      following variables: combination viral prophylaxis, HBV recurrence, tumor stage,
      vascular invasion, distribution, nodularity, pre- and post-OLT tumor size, pre
      OLT alpha-fetoprotein (AFP), Milan and UCSF criteria, and Asian race. RESULTS:
      Cumulatively, HCC recurrence-free survival was 77%, 62%, and 53% at 1, 3, and 5
      years, respectively, and was significantly better in patients who were free of
      viral recurrence post-OLT. Similarly, patients treated with combination
      prophylaxis had a significantly lower mortality than those who were not.
      CONCLUSIONS: Multivariate analysis revealed that AFP>500 ng/mL, presence of
      vascular invasion by explant, HBV recurrence, and combination prophylaxis were
      independent predictors of HCC recurrence-free survival.

PMID- 18089371
TI  - Sensitive serum parameters for hepatocellular carcinoma recurrence monitoring
      after liver transplantation: a case report.
AB  - Liver cell malignancy can be seen as one of the most common indications for
      hepatic transplantation, but the recurrence potential of the disease
      significantly limits its beneficial effects. Hepatic factors influencing the
      recurrence rate, such as nodule size and criteria wherein transplantations are
      expedited, are still investigated. Pretransplant intraarterial or percutaneous
      treatment seem to be predictive for recurrence-free patient survival. Early
      detection of malignancies via serum parameters as a prognostic factor seems
      promising. This article reports a special case, where despite an elevated,
      sensitive, serum marker profile, no HCC recurrence was detected over a 2-year
      follow-up.

PMID- 18089372
TI  - De novo posttransplantation nonlymphoproliferative malignancies in liver
      transplant recipients.
AB  - The risk of developing de novo malignancies after liver transplantation is around
      1% per year. The incidence varies from 3% to 15%; it is greater than that in the
      general population. The potential causes for cancer after solid organ grafting
      are: chronic immunosuppression and human herpes viral infection. The objective of
      this paper was to review the medical literature about the subject to verify the
      incidence of de novo malignancies in our service. We performed retrospective
      analysis of the medical files of 325 successive patients undergoing orthotopic
      liver transplantation from September 1991 to December 2006. We analyzed the type
      of tumor, the risk factors, the treatment modality, and the patient survivals.
      Recurrences of hepatocellular carcinoma were excluded. There were 5 (1.54%) men
      of average age 50.2 years, and an 80% mortality rate. Their survival time was
      affected by the nature of the tumor and by the late manifestations of intestinal
      obstruction allowing adequate surgical treatment. Four of the patients displayed
      heavy alcohol and tobacco consumption before transplantation. Screening for
      premalignant lesions must be strongly encouraged to achieve better postoperative
      results.

PMID- 18089373
TI  - A clinical-pathological analysis of drug-induced hepatic injury after liver
      transplantation.
AB  - OBJECTIVE: The objective of this study was to investigate the histopathologic
      characteristics and clinical features of drug-induced hepatic injury after liver
      transplantation. METHODS: We retrospectively analyzed histopathologic
      characteristics and clinical features of 160 liver biopsy specimens obtained from
      131 posttransplantation patients who were diagnosed as having drug-induced
      hepatic injury from June 2000 to August 2006 in our center. RESULTS: The
      histopathologic features of drug-induced hepatic injury after liver
      transplantation were characterized as centrilobular hepatocyte edema, fatty
      change, and variable intrahepatic cholestasis. Adverse drug reactions were
      diagnosed between days 5 and 1643 after transplantation, including 44.38%
      (71/160) at 5-30 days, 17.50% (28/160) at 31-90 days, and 38.12 (61/160) at 90
      1643 days. The incidence of hepatic injury due to antifungal drugs, antibiotics,
      antiviral drugs, or other agents was 29.38% (47/160), 22.50% (36/160), 16.25%
      (26/160), and 31.87% (51/160), respectively. Abnormalities in routine liver
      function tests included ALT elevation>300 micro/L in 87 patients (54.38%), ALP
      elevation>300 micro/L in 37 patients (23.13%) or total bilirubin elevation>60
      micromol/L in 36 patients (22.50%). Drug-induced toxic liver injury is
      characterized by a single notable increase in ALT, ALP, or TB, especially ALT.
      Common clinical manifestations were flu, rash, gastrointestinal symptoms, and
      eosinophilia. CONCLUSION: Drug-induced hepatic injury commonly appears within 30
      days or after 90 days posttransplantation. Injury emerging within 30 days is
      always caused by antifungal, antiviral, or antibiotic drugs, whereas it displays
      more complicated reasons after 90 days. Drug-induced hepatic injury shows a
      complex and variable clinical manifestation. According to pathologic findings of
      liver biopsy, adequate drug history, and relationship between drug administration
      and onset of clinical manifestations, clinicians and pathologists can make a
      definitive diagnosis and access the extent of injury.

PMID- 18089374
TI  - Effect of nutrition and body composition on bone density after liver
      transplantation.
AB  - We investigated the relationship between nutrition, body composition, and bone
      mineral density (BMD) in young adults after liver transplantation. METHOD: A
      cross-sectional study involving bone densitometry, anthropometry, and detailed
      food and lifestyle questionnaires. RESULTS: Of 37 patients recruited, 26 were
      male. The mean age was 38.8 (+/-12.3) years, and the posttransplant period was
      7.5 (+/-5.1) years (range 1.3-16.4). A significant proportion of patients (23
      [62%]) were overweight (BMI 25-29.9) or obese (BMI>or=30). A total of 20 (54%)
      patients were osteopenic, and four (11%) had osteoporosis (lumbar spine or total
      body BMD). Lean mass showed a statistically significant correlation with lumbar
      spine and total body BMD in men and women, the most significant being bone
      mineral content, r=0.66, P=.01. The correlation was stronger in females (r=0.81,
      P<.01) than in males (r=0.56, P<.01). The average daily intake of vitamin D,
      total protein, and phosphorus was greater than 100% of the American Dietary
      Reference recommendations, calcium was 90%, and magnesium 56%. There was no
      significant relationship between any nutritional parameter and BMD nor history of
      fractures, steroid use, or length of time from transplantation. CONCLUSION:
      Osteopenia determined by lumbar spine BMD underestimates poor BMD in our
      population of young adults after liver transplant. Maintaining muscle mass may be
      helpful in preserving BMD. The effect of a limited intake of magnesium needs
      further investigation.

PMID- 18089376
TI  - Lessons learned with noninvasive cardiac monitoring for acute rejection.
AB  - INTRODUCTION: Computerized Heart Allograft Rejection Monitoring (CHARM), used for
      noninvasive rejection monitoring in heart transplant recipients, is based on the
      analysis of ventricular evoked response (VER) signals. This study evaluated the
      prognostic validity of the TslewC, a parameter extrapolated from the VER.
      METHODS: During orthotopic heart transplantation (OHT) 2 unipolar, fractally
      coated, screw-in leads implanted epimyocardially were connected to a telemetric
      pacemaker. Recordings of IEGMs were performed routinely at hospital and at
      outpatient visits. Data processing yielded trend curves. TslewC was calculated
      from the tangent of VER. One hundred five patients divided into survivors and
      nonsurvivors, were compared using a two-tailed Student's t test. RESULTS: In the
      final follow-up a significant lower TslewC was observed among patients in the
      nonsurvivor compared with the other group (P<.001). Tests to find an optimal
      prognostic threshold of the TslewC yielded the value of 26 mV. CONCLUSION: TslewC
      functioned as a prognostic factor after OHT. Further studies must provide a
      prognostic threshold to avoid patient visits all 4 weeks. Patients would only
      have to be admitted to the hospital if the TslewC was under this prognostic
      threshold.

PMID- 18089375
TI  - Ethnicity as a predictor of graft longevity and recipient mortality in heart
      transplantation.
AB  - BACKGROUND: There is a dearth of data about the effect of donor and recipient
      ethnicity on survival and rejection rate after clinical heart transplantation,
      although the subject had been partly studied before. We compared the mortality
      and rejection rate among different ethnic groups at our institution. METHODS: In
      retrospect, 525 consecutive donors provided cardiac allografts to adult and
      pediatric patients undergoing orthotropic heart transplantation at a single,
      urban US medical center between 2000 and 2005. Donors and recipients were
      categorized according to ethnicity: African American, Asian, Caucasian, Hispanic,
      and Others (Indian, Mediterranean/Arabic, Afghans). Donor and recipient ethnicity
      as an independent factor and the interaction between them-were examined as a risk
      factor for mortality and rejection after heart transplantation. Mean follow-up
      period was 3.2+/-1.9 years (range, 0.1 to 6.6). All recipients received triple
      immunosuppression consisting of a calcineurin inhibitor, an antiproliferative
      agent, and steroids. No patients received induction immunotherapy. The end points
      of the study were early and late mortality, rejection rate, and rejection-free
      survival time. RESULTS: The overall mortality was 17.3% (91 patients). Recipient
      mortality rate according to donor race was: African American, 23.1%; Asian,
      11.1%; Caucasian, 18.7%; and Hispanic, 14.6%. No statistical significance was
      found, although the mortality differences presented. Recipient mortality with
      regard to recipients ethnicity was: African American, 22.2%; Asian, 6.3%;
      Caucasian, 18%; Hispanic, 18.9%; and others 40% (P=.048). Donor-recipient race
      match was not found as a risk factor influencing mortality as the matched group
      mortality was 17.5% comparing with the mismatched group mortality of 17.8%
      (P=.874). The overall rejection rate was 3.8% (20 rejection events). Rejection
      rate according donor race was: African American, 7.7%; Asian, 10.7%; Caucasian,
      4%; and Hispanic, 1.3% (P=.027). Rejection rate with respect to recipients
      ethnicity was: African American, 0; Asian, 3.2%; Caucasian, 4.4%; Hispanic, 2.7%;
      and others, 20% with no statistical significance (P=.236). Donor recipient race
      match was not found as a risk factor influencing rejection rate (P=.58).
      CONCLUSIONS: Recipients' ethnicity was found as a significant risk factor for
      mortality. Rejection rate were found higher among the African American donors and
      significantly lower in the Hispanic donors. Significantly lower mortality rate
      was found among Asian recipients. Donor-recipient race match did not influence
      the mortality or rejection rate.

PMID- 18089377
TI  - Economic evaluation of everolimus and mycophenolate mofetil versus azathioprine
      in de novo heart transplantation.
AB  - Both the proliferation signal inhibitor everolimus (1.5 mg/day) and mycophenolate
      mofetil (MMF) (3 g/day) have shown superior efficacy versus azathioprine in de
      novo heart transplantation. The cost-effectiveness of everolimus and MMF versus
      azathioprine was assessed to 6 months posttransplantation. METHODS: The
      evaluation was performed from the German health insurance payer perspective. The
      composite efficacy endpoint in the everolimus trial was death, graft
      loss/retransplantation, biopsy-proven acute rejection (BPAR) grade>or=3A,
      rejection with hemodynamic compromise, and loss to follow-up. The composite
      endpoint in the MMF trial included only death, retransplantation, and BPAR with
      hemodynamic compromise. To mimic the everolimus endpoint, an estimated number of
      patients with BPAR>or=3A was added to the MMF trial results, using two mapping
      scenarios. RESULTS: The incremental 6-month cost versus azathioprine was euro2535
      for everolimus and euro3007 for MMF. The absolute reduction in efficacy failure
      versus azathioprine was 10.4% for everolimus and 9.8% and 10.1% for MMF,
      respectively, using scenarios 1 and 2. The incremental cost per efficacy failure
      avoided (ie, the incremental cost versus azathioprine divided by the reduction in
      efficacy failure) was euro24,457 for everolimus, and euro30,628 and euro29,912
      for MMF in scenarios 1 and 2. CONCLUSION: This analysis, based on findings from
      two clinical trials, suggested that everolimus was more cost-effective than MMF
      versus azathioprine in the first 6 months after heart transplantation. Data from
      a head-to-head trial are required to confirm these results.

PMID- 18089378
TI  - A prediction model for estimating pulmonary oxygen uptake during the 6-minute
      walk test in organ transplant recipients.
AB  - We developed a multivariate prediction equation for estimating the highest
      obtainable pulmonary oxygen uptake (VO2p) during the 6-minute walk test (6-MWT)
      in 54 organ transplant recipients: heart/heart-double-lung (n=14), kidney/kidney
      pancreas (n=16), liver (n=14), double lung (n=8), bone marrow (n=2). They were of
      age, 48+/-12 years. Participants performed a 6-MWT during which expired gases
      were collected and analyzed with a portable metabolic system interfaced with a
      wireless heart rate monitor. The following variables significantly contributed to
      the model for predicting the highest obtainable 6-MWT VO2p: 6-MWT distance (m),
      age (years), gender (male=0, female=1), resting heart rate, peak heart rate,
      weight (kg), and transplant type (kidney/kidney-pancreas=1, other=0), where:
      VO2p=1.253+0.022 (6-MWT distance)+0.112 (age) -3.192 (gender) -0.104 (resting
      heart rate)+0.127 (peak 6-MWT heart rate)-0.084 (weight)+2.116 (transplant type).
      The explanatory variables in our final model accounted for 78% of the variance in
      6-MWT VO2p. In conclusion, the addition of an easily estimated 6-MWT VO2p will
      provide added clinical information of functional capacity following an exercise
      rehabilitation intervention or during routine follow-up for organ transplant
      recipients.

PMID- 18089379
TI  - Factors related to postoperative mortality in lung transplantation for emphysema.
AB  - BACKGROUND: Chronic obstructive pulmonary disease is the primary indication for
      lung transplantation worldwide. In this study, we analyzed the early outcomes of
      patients with emphysema undergoing bilateral lung transplantation at our center.
      METHODS: This retrospective analysis included 79 consecutive bilateral lung
      transplantation performed due to emphysema (8 with alpha-1 antitrypsin [AAT]
      deficiency) between 1993 and 2005. We analyzed variety of demographic, clinical,
      respiratory function, and surgical variables. Early mortality was defined as
      death occurring in the first month after lung transplantation. Statistical
      analysis included Student t test and Fisher exact test. RESULTS: Seventy-nine
      patients with emphysema, 74 men and 5 women, with a mean FEV1 of 21.1%+/-6.3%,
      underwent bilateral lung transplantation. Fourteen patients (17.7%) died in the
      first month after surgery. Compared with survivors, patients who died in the
      first month, had longer ischemic times (365+/-60 vs 295+/-55 minutes; P=.01),
      needed more cardiopulmonary bypass (69.2% vs 6.2%; P<.0001), and had a greater
      incidence of hemothorax (46.2% vs 10.9%; P=.007). Patients with ischemic time
      longer than 6 hours had a greater 1-month mortality rate (38.5%) than those with
      shorter ischemic times (12.9%; P=.03). No preoperative variable was related to 1
      month mortality after bilateral lung transplantation. CONCLUSIONS: In our
      experience, 1-month mortality after bilateral lung transplantation in emphysema
      was higher among patients with more than 6 hours of ischemic time, those
      undergoing cardiopulmonary bypass, and those developing posttransplantation
      hemothorax.

PMID- 18089380
TI  - A prospective cross-over study comparing the pharmacokinetics of cyclosporine A
      and its metabolites after oral versus short-time intravenous cyclosporine A
      administration in pre-heart transplant patients.
AB  - Sometimes intravenous administration of cyclosporine (CsA) is essential before
      oral administration is possible. There are only a few reports available on the
      interindividual variability of CsA metabolism and different metabolite pattern
      depending on intravenous versus oral administration of CsA in heart transplant
      (HTx) patients. For effective inhibition of calcineurin we used a short infusion
      reaching peak concentrations after 2 hours. In a prospective cross-over study we
      compared the pharmacokinetics of CsA and its metabolites after oral (2.0 mg/kg
      body weight) versus intravenous (0.7 mg/kg body weight; 2-hour infusion) CsA
      administration (single test dose) in 7 pre-HTx patients. The pharmacokinetic
      parameters of CsA and its metabolites were analyzed using high-pressure liquid
      chromatography. The pharmacokinetic parameter area under the concentration time
      curve (AUC(0-infinity)) of CsA after intravenous administration was significantly
      lower (2903 ng*h*mL(-1)) than that after oral administration (4344 ng*h*mL(-1);
      P=.01). Peak concentrations, time to peak concentration, and terminal elimination
      half life were not significantly different. Short-time infusion of CsA resulted
      in a significant decrease in the AUC of the metabolites AM1 (3-fold), AM9 (10
      fold), and AM1c (3-fold). A 2-hour infusion of CsA is just as effective as oral
      administration and the reduced amount of metabolites is advantageous for the
      patient.

PMID- 18089381
TI  - C2 therapeutic drug monitoring of cyclosporine is a safe and feasible method in
      de novo heart transplant patients.
AB  - BACKGROUND: The narrow therapeutic window of cyclosporine (CsA) requires close
      therapeutic drug monitoring (TDM). While C2-TDM has been established after renal
      and liver transplantations, clinical experience is limited for patients after de
      novo heart transplantation (HTX). PATIENTS AND METHODS: In a retrospective study,
      we investigated 40 patients undergoing HTX; 34 patients received induction
      therapy using antithymocyte globulin (ATG Merieux). Immunosuppression was
      administered with CsA (Sandimmun-Optoral), with dosages adjusted according to C2
      levels (800-1100 ng/mL during the first 6 months and reduced to 400-600 ng/mL
      from the beginning of the first year). At different times TI (months 1-3). TII
      (months 12-14) TIII (months 24-26), and TIV (months 34-36), we obtained measures
      of acute cellular rejections (ARs), cytomegalovirus (CMV) infections, creatinine,
      and safety laboratory parameters. RESULTS: The cumulative survival was 95% after
      1 year, and 88% after 3.8 years. Eight ARs were diagnosed at a mean of 7.6 months
      after HTX in 7 patients. Twenty-four CMV infections/reactivations were verified.
      In 10 cases, treatment was started because of clinical symptoms. The mean
      creatinine values significantly rose in the early postoperative phase (TI: 1.23+/
      0.47 mg/dL, TII: 1.49+/-0.41 mg/dL; P<.0001). Thereafter the creatinine values
      declined; however, this was not statistically significant (TIII: 1.38+/-0.57
      mg/dL, TIV: 1.15+/-0.30 mg/dL). All other safety parameters showed no significant
      changes. CONCLUSIONS: C2 allows individualization of immunosuppression with
      reduced CsA toxicity, but without loss in safety among de novo patients after
      HTX. We obtained freedom from severe AR, a low number of CMV infections, and
      excellent patient survival.

PMID- 18089382
TI  - Assessment of cyclosporine pharmacokinetic parameters to facilitate conversion
      from C0 to C2 monitoring in heart transplant recipients.
AB  - BACKGROUND: Cyclosporine (CsA) 2-hour postdose (C2) monitoring is recommended to
      assess CsA exposure and predict clinical outcomes among heart transplant
      recipients. We correlated pharmacokinetic parameters and clinical outcomes in
      stable long-term heart transplant recipients monitored with C0 to develop an
      algorithm to convert patients from C0 to C2 monitoring. METHODS: Paired CsA C0-C2
      measurements and serum creatinine levels were obtained from 35 heart transplant
      recipients more than 2 years posttransplantation (mean 8.8+/-4.7 years). RESULTS:
      The mean CsA dose and C0, C2, and C0/C2 ratio were 85+/-23 mg/12 hours, 123+/-41
      ng/mL, 572+/-274 ng/mL and 4.8+/-2.1, respectively. C0 correlated weakly with C2
      (r=.42, P=.011). The CsA dose correlated better with C2 (r=.58; P<.001) than with
      C0 (r=.37; P=.026). A good correlation was noted between C2 and the C2/C0 ratio
      (r=.73; P<.001), but none between C0 and the C2/C0 ratio. A borderline
      significant inverse correlation was noted between C0 and the worst endomyocardial
      biopsy score (r=-.34; P=.045), whereas none was noted with C2. Serum creatinine
      level did not correlate with either C2 or C0. Among patients with C0 within our
      target of 100 to 150 ug/L, six had C2 above 300 to 600 ug/L as suggested by the
      literature. CONCLUSIONS: In long-term heart transplant recipients, we could not
      identify a single pharmacokinetic parameter that could be used to develop an
      algorithm to convert from C0 to C2 monitoring; however, C2 may be better than C0
      for identifying patients at risk of overexposure to CsA.

PMID- 18089383
TI  - Strategy of aggressive steroid weaning and routine alendronate therapy to reduce
      bone loss after cardiac transplantation.
AB  - OBJECTIVE: Osteoporosis is common after cardiac transplantation. The routine use
      of prednisolone posttransplantation is a major contributor to bone mineral loss.
      We sought to study the effectiveness of a strategy combining aggressive steroid
      weaning and routine prophylaxis with alendronate to reduce bone loss without
      adversely affecting posttransplantation survival. PATIENTS AND METHODS: This
      retrospective clinical study compared 2 cohorts of patients. Group A included 28
      patients who had undergone transplantation since June 1999, all of whom were
      prescribed alendronate (10 mg daily or 70 mg weekly). All were aggressively
      weaned off prednisolone with the aim of being steroid-free by 9 months
      posttransplantation. Only 10 of the 28 patients were on prednisolone at the time
      of the study. Group B was an historical control cohort of 28 posttransplant
      patients reviewed in a cross-sectional study in 1995. Only 2 patients were on
      osteoporosis prophylaxis with estrogen or vitamin D; 26 patients were on
      prednisolone at the time of the study. The groups were compared by dual-energy X
      ray absorptiometry (DEXA) bone mineral densitometry at the femoral neck and
      lumbar spine at a mean of 3 years after transplantation. We compared the
      cumulative survival of the 2 groups. RESULTS: Cumulative survival
      posttransplantation was similar in both groups. Compared with group B, group A
      showed a significantly higher mean femoral Z-score (+0.3 vs -0.5, P=.01) and
      lumbar spine Z-score (0.0 vs -0.9, P<.02). The incidence of osteoporosis (defined
      by WHO criteria as T-score<or=-2.5) was lower in group A compared with group B
      (18% vs 29%, P=NS). CONCLUSIONS: A strategy of aggressive weaning of prednisolone
      postcardiac transplantation coupled with routine osteoporosis prophylaxis using
      alendronate was associated with significantly higher bone mass and a trend toward
      a reduced incidence of osteoporosis. This strategy was successful to reduce the
      use of steroid without any adverse effect on cumulative survival
      posttransplantation.

PMID- 18089384
TI  - Allogeneic stem cell transplantation in hematological disorders: single center
      experience from Pakistan.
AB  - One hundred and fifty-four patients received allogeneic stem cell
      transplantations from HLA-matched siblings for various hematological disorders
      from July 2001 to September 2006. Indications for transplantation included
      aplastic anemia (n=66), beta-thalassemia major (n=40), CML (n=33), acute leukemia
      (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were
      males and 34 were females. Median patient age was 14 years (range, 1(1/4)-54
      years). All patients achieved successful engraftment. Median time to engraftment
      (ANC>0.5x10(9)/L) was 14 days. Posttransplant complications encountered in our
      patients included acute graft versus host disease (GvHD) (grade II-IV) 28.5%,
      chronic GvHD 15.5%, hemorrhagic cystitis 9.7%, VOD liver 5.1%, acute renal
      failure 3.2%, bacterial infections 51.2%, fungal infections 15.0%,
      cytomegalovirus (CMV) infection 4%, herpes zoster 4%, tuberculosis 2.6%,
      Pneumocystis jirovicii infection 0.6%, malaria 0.6% patients, graft rejection
      5.2% patients, and relapse in 4% patients. Certain unexpected and rare
      posttransplant complications were also observed in our patients. These included
      Hickman catheter embolization, Guillain-Barre (GB) syndrome, deep vein
      thrombosis, hemorrhagic pericarditis with clots leading to cardiac tamponade,
      idiopathic polycythemia, dengue fever, and cyclosporine-induced neurotoxicity.
      Mortality was observed in 27.2% patients. Major causes of mortality were GvHD,
      VOD, disease relapse, intracranial hemorrhage, acute renal failure, pseudomonas
      septicemia, tuberculosis, disseminated aspergillosis, and CMV infection. At 5
      years, overall survival (OS) and disease-free survival (DFS) rates were 72.5% and
      70.7%, respectively.

PMID- 18089385
TI  - Favorable response to human adipose tissue-derived mesenchymal stem cells in
      steroid-refractory acute graft-versus-host disease.
AB  - There is no consistently effective therapy for patients with steroid-refractory
      acute graft-versus-host disease (GVHD). Various alternative approaches have been
      tested, including antithymocyte globulin, mycophenolate mofetil (MMF),
      pentostatin, and monoclonal antibodies; however, they have only been modestly
      successful. The purpose of our study was to evaluate the efficacy of human
      adipose-tissue-derived mesenchymal stem cells (AMSC) as salvage therapy for
      steroid-refractory acute GVHD. Six patients with steroid-refractory grades III-IV
      acute GVHD received IV infusions of AMSC. The AMSC dose was 1.0x10(6)/kg. No side
      effects were noted after the AMSC infusions. Five patients were treated once and
      one patient twice. Two patients received AMSC from haplo-identical family donors
      and four from unrelated mismatched donors. Acute GVHD disappeared completely in
      five of six patients, four of whom are alive after a median follow-up of 40
      months (range, 18-90 months) after the initiation of AMSC therapy. All four
      surviving patients are in good clinical condition and in remission of their
      hematological malignancy. Two patients died-one with no obvious response to AMSC
      died of multiorgan failure and one a relapse of leukemia. These results suggested
      that AMSC is a promising treatment for severe steroid-resistant acute GVHD.

PMID- 18089386
TI  - Mesenchymal stem cells contribute to insulin-producing cells upon
      microenvironmental manipulation in vitro.
AB  - BACKGROUND: Extracellular microenvironment and intrinsic genetic programs
      determine the fate of stem cells. We observed whether mesenchymal stem cells
      (MSCs) contributed to insulin-producing cells in a manipulated microenvironment.
      METHODS: We delivered pancreatic pieces into Niobium-Coated Dynamatrix to
      construct a simulated pancreatic microenvironment, upon which soluble cytokine
      exchange and direct cell-cell contact between MSCs and pancreatic cells could
      occur. Bone marrow-derived MSCs were cultured upon the microenvironment.
      Differentiated isletlike cells were observed under an inverted microscope.
      Insulin in supernates was measurement by enzyme-linked immunosorbent assay.
      Insulin and c-peptide expression were verified by fluorescent immunocytochemistry
      and fluorescence in situ hybridization. Apoptosis of isletlike masses in high
      glucose DMEM was detected by FACS. RESULTS: After 3 to 4 weeks in culture,
      typical isletlike masses were observed. Insulin secreted by differentiated cells
      (414.47+/-30.30 mIU/L) was much greater than that of undifferentiated cells
      (4.89+/-1.01 mIU/L; P<.05). Insulin and c-peptide expression were positive both
      in protein and mRNA levels. The transdifferentiated isletlike mass did not
      undergo apoptosis after another 3 weeks of culture in high-glucose DMEM.
      CONCLUSION: This simulated injury microenvironment without induction guided MSCs
      to functional isletlike cells hopefully to replace beta cells.

PMID- 18089387
TI  - A magnetic resonance imaging study of iron overload in hemopoietic stem cell
      transplant recipients with increased ferritin levels.
AB  - We performed a study of magnetic resonance imaging (MRI) assessment of
      hemosiderosis in the heart (T2/T2*), liver (T2*), pancreas (T2*), and pituitary
      gland (T2/T2*/SIR) in 20 hemopoietic stem cell transplant (HSCT) recipients
      (median peak ferritin levels 7615 pmol/L, range 3411 to 33000 pmol/L). MRI
      reading was abnormal in the heart (5%), liver (85%), pancreas (40%), and
      pituitary gland (55%). The heart T2 correlated with peak ferritin levels
      (P=.024), while the liver T2* correlated with current ferritin (P=.038) values
      only. Pancreatic T2* values correlated with pituitary T2 and signal intensity
      ratio values. The ejection fraction was abnormal in 10% of cases and did not
      correlate with ferritin level or heart T2. The peak liver enzymes correlated with
      peak ferritin (P=.025), but the current liver enzymes were mostly normal.
      Pancreatic assessments (fasting glucose, insulin, beta cell function, insulin
      reserve, and C-peptide) and pituitary growth hormone axis assessments (growth
      hormone, insulin growth factor-1, and insulin growth factor binding protein-3)
      were abnormal in 40% to 70% of cases. They were unrelated to pancreas or
      pituitary MRI values. Interestingly, endocrine assessments correlated with heart
      T2 values and peak (but not current) ferritin levels. We concluded that iron
      overload may contribute to organ damage after HSCT, and MRI assessment may be
      useful in its detection and treatment monitoring.

PMID- 18089388
TI  - Prediction of nonrelapse mortality for patients surviving 100 days after
      allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND: Patients who survive 100 days after allogeneic hematopoietic stem
      cell transplantation (alloHSCT) are at risk for chronic graft-versus-host disease
      and other potentially fatal complications. As the symptoms overlap and the
      differential diagnosis is difficult, the goal of this study was to verify whether
      basic laboratory evaluation performed on day +100 may allow identification of
      patients who are at high risk for nonrelapse mortality (NRM), independent of the
      underlying complications. PATIENTS AND METHODS: We analyzed 255 patients, mean
      age 29 years (range, 10-56 years), who remained alive and disease-free on day
      +100 after myeloablative alloHSCT from an HLA-identical sibling (n=177) or a
      matched unrelated volunteer (n=78), performed in a single institution between
      1992 and 2003. RESULTS: Upon univariate analysis, the following laboratory
      parameters were associated with increased incidence of NRM: peripheral blood
      neutrophils<1.5x10(9)/L, platelets<100x10(9)/L, hemoglobin<11 g/dL, total
      protein<60 g/L, elevated plasma aspartate aminotransferase, elevated alkaline
      phosphatase, and elevated bilirubin. Upon multivariate analysis, only decreased
      protein (hazard ratio [HR]=6.97 [3.3-14.7], P<.0001) and elevated bilirubin
      (HR=3.52 [1.91-6.48], P<.0001) independently influenced the risk for NRM. The
      cumulative incidence of NRM equaled 6% if none of the above factors was present;
      10% for hyperbilirubinemia alone; 22% for hypoproteinemia alone; and 70% for
      hyperbilirubinemia and hypoproteinemia, both present. CONCLUSIONS: A simple
      laboratory evaluation is highly predictive of the risk for NRM in patients
      surviving 100 days after alloHSCT. The prognosis is particularly poor for
      patients with hypoproteinemia and hyperbilirubinemia. These abnormalities may
      reflect impaired liver and intestine functions due to various posttransplantation
      complications.

PMID- 18089389
TI  - Cell recovery sufficient for adult transplantation by additional cord blood
      collection from placenta.
AB  - The amount of newborn blood that can be collected from a single cord donor is
      limited, but a significant amount remains in the placenta. We used a simplified
      perfusion method to collect this additional blood. Umbilical cord blood from 15
      newborns was collected before placental delivery by umbilical vein puncture.
      After delivery, the placenta was placed on sterile gauze and 63 mL of citrate
      phosphate-dextrose-adenine anticoagulant were injected into the umbilical vein
      that was then clamped near the placenta. The placenta was gently massaged, hung
      over a sterile vessel, and the umbilical cord cut sterilely near the embryonic
      surface. Additional blood was collected into the sterile vessel by pressuring a
      gauze bag around the placenta. We assessed the contribution of this second
      fraction to the total volume, total nucleated cell (NC), CD34+, hematopoietic
      progenitors cell, and colony forming unit count and bacterial contamination risk.
      The total collected volume was 127.3 mL (range 92-170) and the NC content was
      1.6+/-0.73x10(9). The mean second fraction contribution from 15 units to the
      total nucleated and mononuclear cell content was 54+/-9.87% and 54+/-9.52%,
      respectively. The added percentage of CD34+ and hematopoietic progenitor cells
      was 54.3+/-10.35% and 46.7+/-11.5%, respectively, while the additional
      percentages of colony forming-granulocyte macrophage and colony forming-erythroid
      in the second fraction were 43.2+/-5.5% and 39.8+/-4.3%, respectively, indicating
      that the cells collected after placental perfusion (second fraction) had similar
      HPC content and in vitro hematopoietic potential. The method did not increase the
      risk of bacterial contamination.

PMID- 18089390
TI  - Renal event outcomes in intestinal transplantation: results from a single-center
      experience.
AB  - BACKGROUND: Poor patient outcomes have been closely linked with perioperative
      renal function after most solid organ transplants, except intestinal
      transplantation (ITx). This study examined the effect of peri-ITx renal function
      on outcome. PATIENTS AND METHODS: A retrospective review of all patients
      undergoing ITx since 1991 was completed and included 43 patients and 49
      transplants. Serum creatinine (sCr) and calculated glomerular filtration rate
      were compared with peri-ITx and out to 5 years. A renal event (RE) was defined as
      acute renal failure, immunotherapeutic change driven by poor renal function, or
      hemodialysis. Comparisons were made based on primary immunotherapeutic regimens
      induction interleukin-2 receptor antagonist (IL-2RA; n=31) or standard tacrolimus
      based therapy (STD; n=18). Data was analyzed using standard statistical analysis.
      RESULTS: The frequency of RE was: 60% (STD) versus 31% (IL-2RA) P<.05. RE
      associated mortality was 63% (STD) and 27% (IL-2RA) P<.05. Overall mortality was
      associated with a RE in 50% (STD) and 37% (IL-2RA) of patients. Average sCr
      across all timepoints was 1.05 (STD) and 0.78 (IL-2RA) P<.003. Surviving patients
      with RE in STD tended to suffer prolonged renal insufficiency, whereas those in
      IL-2RA did not. CONCLUSION: This is the first study examining outcomes after ITx
      related to renal function. Clearly, renal function and RE impacted outcomes.
      Obtaining RE-free survival and lessening the impact of RE when they do occur is
      of paramount importance. It appears that IL-2RA immunotherapy reduces RE and
      their associated morbidity.

PMID- 18089391
TI  - Gene transfer of antisense B7.1 attenuates acute rejection against splenic
      allografts in rats.
AB  - Blockade of CD80-CD28 costimulatory pathway induces unresponsiveness of T cells
      to alloantigens and protects allografts against immune rejection in numerous
      animal models. The aim of this study was to investigate whether blocking
      expression of B7.1 (CD80) on donor splenocytes by an antisense technique
      protected splenic allografts against immune rejection. Splenic grafts from Wistar
      Furth rats were intra-arterially transfused with an antisense B7.1 expression
      vector, before they were transplanted into Sprague-Dawley rats. The rats were
      sacrificed at scheduled times, and the splenic allografts histologically
      examined. Antisense gene transfer resulted in marked down-regulation of B7.1 in
      donor spleens, hyporesponsiveness of recipient T cells, and attenuated acute
      immune rejection against splenic allografts. No obvious damage to skin, liver, or
      gut due to graft-versus-host disease was detected in the recipients. In
      conclusion, blocking expression of B7.1 in donor spleens by antisense gene
      therapy represented a potential alloantigen-specific immunosuppressive strategy
      to inhibit acute rejection against splenic allografts.

PMID- 18089392
TI  - The protective effect of CD8+CD28- T suppressor cells on the acute rejection
      responses in rat liver transplantation.
AB  - Regulatory T cells (Tr) or T-suppressor cells (Ts), which include CD4+CD25+ T
      cells and CD8+CD28- T cells respectively, have been shown to be essential for the
      induction and maintenance of immune tolerance. We have investigated the effect of
      CD8+CD28- Ts and CD4+CD25+ Tr on acute rejection responses in rat liver
      transplantation (OLT). METHODS: CD8+CD28- Ts/CD4+CD25+ Tr were obtained from
      inbred and naive rats that show spontaneous tolerance to OLT. Adoptive transfers
      were performed in acute rejection models of various strain combinations with
      survival times observed to evaluate suppressive effects. Donor-specific blood
      transfusion (DST) was used to induce CD8+CD28- Ts in naive rats, which were
      assayed in vitro using carboxyfluorescein diacetate succinimidyl easter-labeled
      one-way mixed lymphocyte reactions. Secondary adoptive transfers of DST-induced
      CD8+CD28- Ts were also performed in an acute OLT rejection model. RESULTS:
      CD8+CD28- Ts from tolerant OLT model rats possessed immunosuppressive activity in
      allogeneic recipients; adoptive transfers of these cells alleviated the acute
      rejection responses. However, CD4+CD25+ Tr derived from tolerant or naive rats
      failed to do so. In vitro DST-induced CD8+CD28- Ts inhibited alloantigen T-cell
      responses in naive syngeneic rats in an antigen-specific manner. Secondary
      adoptive transfer of DST-induced CD8+CD28-Ts further reduced acute rejection but
      not chronic rejection responses. CONCLUSIONS: CD8+CD28- Ts cells protected
      allogeneic recipients from acute rejection in rat OLT. Furthermore, this activity
      was not present in CD4+CD25+Tr. DST was observed to be an effective method to
      generate functional CD8+CD28-Ts in naive rats.

PMID- 18089393
TI  - Mesenchymal stem cells modulate immune responses combined with cyclosporine in a
      rat renal transplantation model.
AB  - Mesenchymal stem cells (MSCs) are pluripotent progenitors for a variety of cell
      types. Their down-regulation of the immune response in vivo has been
      hypothesized, but not yet substantiated, by experimental evidence. We
      investigated graft function, histology, animal survival days reverse
      transcriptase-polymerase chain reactor (RT-PCR) analysis of interleukin (IL)-1,
      tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta1.
      The results demonstrated that MSCs down-regulated immune responses, reduced
      production of some inflammatory mediators, preserved graft function in the
      initial stage after transplantation, and prolonged animal survival. However, the
      effects were not as strong as those of cyclosporine (CsA) therapy. Moreover, MSCs
      combined with low-dose CsA protected graft function, but could not prolong animal
      survival compared with CsA monotherapy, indicating a potential interaction
      between MSC and CsA activities, possibly allowing reduced CsA doses.

PMID- 18089394
TI  - Construction and functional evaluation of an autologous thymokidney model in the
      rat.
AB  - BACKGROUND: We constructed a rat model of stable autologous thymokidney to
      observe the time required for revascularization and to examine functional
      recovery of the transplanted tissue and the reconstruction of T-cell reservoirs
      in peripheral blood mononuclear cells. MATERIALS AND METHODS: Male adult Sprague
      Dawley rats were divided into groups. Group I (n=12, 150 to 250 g) underwent
      thymectomy, group II (n=15, 150 to 250 g) received an autologous thymokidney in
      which thymic tissue was transplanted under the renal capsule, group III (n=5, 50
      to 100 g) received sham surgery, and group IV (n=5) consisted of rats selected
      from group 1 to undergo splenectomy 8 weeks after thymectomy. Revascularization
      and functional recovery of the transplanted thymuses were evaluated with flow
      cytometry and histomorphologic examination. RESULTS: Two weeks after surgery,
      blood vessels grew into the renal capsules in group II, the transplanted thymic
      tissue thickened at 8 weeks, and thymic structure was normal. At 6 weeks, numbers
      of CD4-CD8- T lymphocytes increased in group I and especially in group IV. A
      gradual decrease was noted in group II. Numbers of CD4+ and CD8+ T lymphocytes
      fluctuated at low levels in group I but stayed constant in group II. The
      transplanted thymuses began to gradually degenerate 12 to 16 weeks after surgery.
      CONCLUSIONS: Thymuses transplanted under the renal capsules adequately
      revascularized 2 weeks after surgery, and the autografts began functional
      recovery at 6 weeks. Proliferation of peripheral mature T lymphocytes is
      important in maintaining the number of mature T lymphocytes in peripheral blood
      mononuclear cells.

PMID- 18089395
TI  - Effect of ligustrazine on chronic allograft nephropathy in rats.
AB  - OBJECTIVES: Our previous study demonstrated that Ligustrazine reduced renal
      dysfunction associated with ischemia-reperfusion injury in mice. In this study,
      we investigated whether Ligustrazine herbal injection had any preventive and
      therapeutic effectiveness against chronic allograft nephropathy in rats. METHODS:
      Male Lewis rats that received left renal grafts from male Fisher 344 rats were
      randomly divided into five groups: group A only received cyclosporine (CsA; 10
      mg.kg(-1).d(-1)) every day. Groups B, C, and D received low-dose Ligustrazine (50
      mg.kg(-1).d(-1))+CsA (10 mg.kg(-1).d(-1)); high-dose Ligustrazine (100 mg.kg(
      1).d(-1))+CsA (10 mg.kg(-1).d(-1)); and CsA (10 mg.kg(-1))+mycophanolate mofetil
      (10 mg.kg(-1).d(-1)), respectively. Group E was an isografted group (Fisher 344
      to Fisher 344). Grafts were preserved in 4 degrees C University of wisconsin
      solution for 1 hour prolonged cold ischemia. All recipient animals were
      unilaterally right nephrectomized. Serum creatinine (Scr), blood urea nitrogen
      (BUN), urinary protein, kidney malondialdehyde (MDA) level, and superoxide
      dismutase (SOD) were determined, as well as examining kidney histology with
      immunohistochemistry for Bcl-2, and ICAM-1. Alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) were tested to show whether Ligustrazine has
      side effects. RESULTS: Compared with group E, ischemia and rejection produced a
      ninefold increase in GSR and Banff score, as well as significant increases of
      Scr, BUN, and urinary protein levels in group A. High doses of Ligustrazine
      significantly slowed the increase (P<.01). Ligustrazine also decreased MDA levels
      and ameliorated the down-regulation of SOD activity. Bcl-2 was up-regulated
      posttransplantation, especially in the Ligustrazine-treated group (P<.01). The up
      regulation of ICAM-1 was greatly diminished by Ligustrazine (P<.01). Furthermore,
      there was little difference in ALT/AST between the Ligustrazine-treated and the
      isograft group. CONCLUSION: These findings suggested that Ligustrazine could
      postpone chronic renal allograft dysfunction associated with cold ischemia injury
      and chronic allograft rejection but had no evident hepatic side effects.

PMID- 18089396
TI  - The myofibrosis mechanism of differentiation growth factor-8 on rat abdominal
      aorta grafts.
AB  - OBJECTIVE: The objective of this study was to investigate the role of
      differentiation growth factor-8 (GDF-8) in inhibiting myofibrosis of abdominal
      aorta grafts. METHODS: Male Spague-Dawley (SD) rats that received abdominal aorta
      grafts from male Wistar rats were randomly divided into 2 groups: prolonged cold
      ischemia (PCI) and control groups. Hematoxylin-eosin (HE) staining was performed
      to examine aortic graft morphology and to measure neointimal thickness. RT-PCR
      demonstrated the expression of GDF-8. Immunohistochemical staining (IHC) was
      performed to detect the expression of Smad4, a pivotal molecule of the
      transforming, growth factor-beta (TGF-beta)/Smad signal pathway. RESULTS: The
      intimal thickness increased by 14 days following transplantation in the PCI group
      (P<.05), reaching 381.952+/-44.334 microm at 28 days, which was higher than that
      of the control group (56.898+/-17.543 microm; P<.05). The GDF-8 expression in the
      PCI group was only 3.6%-33.8% of that among the control group. There was a much
      higher expression of Smad4 on the endothelium of the PCI than the control group
      at the same time. CONCLUSIONS: Prolonged cold ischemia accelerated grafts
      myofibrosis by down-regulating the expression of GDF-8, which plays a key role in
      the myofibrosis process of rat abdominal aortic grafts.

PMID- 18089397
TI  - Observation of hepatohilar peribiliary vascular plexus with complete absence of
      hepatic artery blood supply in rats.
AB  - OBJECTIVE: The purpose of this study was to examine the morphologic changes in
      the hepatohilar peribiliary vascular plexus (PVP) and the pathology of the bile
      duct walls after cessation of hepatic artery blood supply in mice. MATERIALS AND
      METHODS: Sprague-Dawley (SD) experimental mice were randomly divided into a
      control and a treatment group. The morphological structure of the hepatohilar PVP
      after cessation of blood supply was observed using ink perfusion transparency
      management with computerized 3 dimensional reconstruction. The inner layer of the
      PVP was analyzed quantitatively and pathological examination was performed on the
      bile duct wall. RESULTS: The treatment group showed disorder of the 3-dimensional
      hepatohilar PVP structure with a markedly reduced number of micrangium in the
      inner layer (P<.01). The number of arterioles in the inner layer of PVP also
      trended downward (P<.05) and there was chronic hyperplastic inflammation in each
      layer of the vascular wall. CONCLUSION: Without an arterial blood supply
      containing a high oxygen content, the morphologic structure of the PVP changes,
      producing consequent pathology in the bile duct wall.

PMID- 18089398
TI  - Additive immunosuppressive effect of hydroxycamptothecin and cyclosporine on
      rejection of heart transplantation in rats.
AB  - OBJECTIVE: The objective of this study was to study the inhibitory effects of
      hydroxycamptothecin (HCPT) and cyclosporine (CsA) on heart transplantation
      rejection in rats. MATERIALS AND METHODS: Inbred SD rats were used as donors and
      inbred Wistar rats as recipients. Cervical heterotopic heart transplantation was
      performed in 40 rats: group A received placebo; group B, HCPT; group C, CsA;
      group D, HCPT+CsA. RESULTS: The mean survival time was prolonged in group D with
      5 grafts beating at more than 730 days. CONCLUSION: HCPT combined with CsA
      prevented acute rejection of allogeneic heart transplantations in rats,
      significantly prolonging graft mean survival time.

PMID- 18089400
TI  - Prolongation of islet allograft survival by coexpression of CTLA4Ig and CD40LIg
      in mice.
AB  - BACKGROUND: B7/CD28 and CD40/CD40L have been well established as important
      costimulatory pathways. Cytotoxic T lymphocyte-associated antigen-4 (CTLA4)
      delivers negative signals to antigen-presenting cells to down-regulate
      proinflammatory responses and competitively inhibits the binding of B7 and CD28.
      Signals from the CD40/CD40L costimulatory pathway also play an important role in
      acute rejection of organ grafts. METHODS: Recombinant adenoviruses Ad-sCD40LIg
      IRES2-CTLA4Ig, Ad-CTLA4Ig, and Ad-sCD40LIg were constructed to express sCD40LIg
      and CTLA4Ig simultaneously or separately as described previously. Streptozocin
      induced diabetic BALB/c mice were injected with recombinant adenovirus, receiving
      approximately 500 donor islets isolated from C57BL/6 mice under the left kidney
      capsule. Five groups were assigned according to the treatment: nontreated group,
      Ad-Shuttle-CMV-treated group, Ad-CTLA4Ig-treated group, Ad-sCD40LIg-treated
      group, and Ad-sCD40LIg-IRES2-CTLA4Ig-treated group. The islet graft mean survival
      time (MST) was evaluated in the present study. RESULTS: Compared to the islet
      graft MST of the nontreated group (7.3+/-0.82 days) or Ad-Shuttle-CMV-treated
      group (7.2+/-1.47 days), the Ad-CTLA4Ig-treated and Ad-CD40LIg-treated islet
      graft survivals in recipients were 56.3+/-13.71 days (P<.01) and 47.3+/-15.64
      days (P<.05), respectively. The islet graft MST was dramatically prolonged to
      116.3+/-20.32 days in the Ad-sCD40LIg-IRES2-CTLA4Ig-treated group (P<.01).
      CONCLUSION: Simultaneous blockade of the CD40/CD40L and B7/CD28 costimulatory
      pathways via coexpression of sCD40LIg and CTLA4Ig mediated by replication
      defective adenovirus may be an acceptable method to induce immune tolerance.

PMID- 18089399
TI  - Effect of FTY720 and ex vivo graft irradiation in rat small bowel
      transplantation: apoptosis of crypt cells and lymphocytes.
AB  - OBJECTIVE: We investigated the extent of apoptosis in crypt cells and Peyer's
      patches (PPs) during small bowel allograft rejection in rats to examine the
      effect of FTY720 and ex vivo graft irradiation during rejection. MATERIALS AND
      METHODS: Orthotopic small bowel transplantations (SBT) were performed from Brown
      Norway (BN) rats to Lewis (LEW) rats. Four groups of SBT animals were studied on
      days 3, 5, and 7 after operations: untreated allograft, allograft with FTY720,
      allograft with irradiation, and allograft with FTY720+irradiation. Cryostat
      sections were prepared from the grafts, including PPs. An in situ end-labeling
      (ISEL) technique was used to detect apoptotic cells. Indirect immunoperoxidase
      staining was also performed using monoclonal antibodies against rat Fas/FasL.
      RESULTS: The graft survival was prolonged in the FTY720-treated groups. In the
      FTY720-treated group, the number of ISEL-positive enterocytes was significantly
      down-regulated on days 3, 5, and 7 compared with the untreated allograft group.
      The number of ISEL-positive mononuclear cells was also significantly down
      regulated compared with the untreated allograft group. The FTY720 the radiation
      and the FTY720+irradiation treated groups showed significantly down-regulated
      numbers of Fas/FasL-positive enterocytes on day 7 compared with the untreated
      allograft group. Fas/FasL-positive mononuclear cells were also significantly down
      regulated in the allograft compared with the untreated allograft group.
      CONCLUSIONS: FTY720 and ex vivo graft irradiation prevented up-regulation of the
      number of apoptotic enterocytes, lymphocytes, and Fas/FasL-positive lymphocytes,
      and also prolonged small bowel allograft survival. Combination FTY720 and ex vivo
      graft irradiation did not affect graft survival and apoptotic cell expression
      compared with the FTY720 only group. These findings suggest that FTY720 may
      prevent both rejection-associated and sepsis-induced apoptosis during the late
      phase of small bowel graft rejection.

PMID- 18089401
TI  - An animal model of human cytomegalovirus infection.
AB  - To develop a rat model that allowed in vivo progressive human cytomegalovirus
      (HCMV) infection, allogeneic liver transplantation was performed across a rat
      combination of Dark Agouti (DA) to Brown Norway (BN). AD169, a well-characterized
      laboratory strain of HCMV, was used to establish a rat model of HCMV infection by
      injection of 0.4 mL (30.0 logTCID50) supernate into the rat peritoneum.
      Histological and blood specimens were obtained from animals sacrificed at
      predetermined timepoints. We performed immunohistochemical staining in liver,
      heart, kidney, spleen, and lung for HCMV immediate-early antigen (IE), lower
      matrix protein (pp65) detection in peripheral blood leukocytes, and HCMV early
      antigen (EA) and late antigen (LA). We compared survival rates. Our results
      showed positive HCMV IE and pp65 antigenemia detected in peripheral blood
      leukocytes in transplanted recipients from day 1 to day 30. Positive HCMV EA and
      LA staining cells were only detected in sections 10 days after liver
      transplantation, namely, in hepatocytes, mononuclear cells, bile duct epithelial
      cells, and endothelial cells. Successful HCMV replication was due to the
      combination of liver transplantation and cyclosporine (CsA) immunosuppression.
      Survival analysis showed no significant differences between the HCMV-infected
      group and HCMV-uninfected group. This new rat model of HCMV infection may be
      helpful to understand immune system modulation of HCMV infection.

PMID- 18089402
TI  - Fibronectin suppresses lipopolysaccharide-induced liver damage and promotes the
      cytoprotection abilities of hepatocyte-like cells derived from human bone marrow
      mesenchymal stem cells.
AB  - We isolated mesenchymal stem cells (MSCs) from adult human bone marrow. By using
      reverse-transcription polymerase chain reactions, we confirmed that MSCs
      possessed the potential to differentiate into hepatocyte-like cells (MSC-HLCs)
      with the expression of hepatocyte-specific marker genes. We further observed that
      fibronectin (FN) treatment significantly inhibited lipopolysaccharide (LPS)
      induced apoptotic activities in FN-treated MSC-HLCs, as detected by caspase 3
      enzyme-linked immunosorbent (ELISA) and terminal dUTP nick-end labeling (TUNEL)
      assays (P<.05). The FN-treated MSC-HLCs were transplanted into SCID mice with or
      without LPS injection. This study demonstrated that FN treatment improved liver
      function repair and survival rates among LPS-treated SCID mice.

PMID- 18089403
TI  - Adenovirus-mediated heme oxygenase transfer inhibits graft arteriosclerosis in
      rat aortic transplants.
AB  - PURPOSE: Heme oxygenase-1 (HO-1) has been implicated in graft protection because
      its induction is associated with long-surviving allografts. The aim of this study
      was to analyze the efficacy of adenovirus-mediated HO-1 overexpression to inhibit
      graft arteriosclerosis and estimate whether the protective role correlated with
      nuclear factor kappaB (NF=kappaB) expression and grafts apoptosis. METHODS:
      Aortic transplantation was performed using inbred Brown-Norway (BN) rats (RT1n
      male) as donors and Lewis rats (RT1l male) as recipients. The experiments were
      divided into four groups: group A, Lewis-Lewis (n=6), no treatment; group B, BN
      Lewis (n=6), no treatment; group C, BN-Lewis (n=6), donor aorta perfused with
      buffer containing 4x10(10) pfu Ad-Null (the noncoding adenoviral vector); and
      group D, BN-Lewis (n=6), donor aorta perfused with buffer containing 4x10(10) pfu
      Ad-HO-1 (adenoviral vector coding for HO-1). All grafts were harvested at 60 days
      after transplantation. Reverse transcriptase polymerase chain reaction was
      performed to detect the expression of HO-1 gene. Hematoxylin and eosin staining
      was used to detect the morphology and cytology of the transplanted vessels.
      Intimal thickening was detected by Masson staining. Immunohistochemistry was used
      to detect the localization and expression of HO-1 and NF-kappaB and TUNEL assays
      to detect the apoptosis of the grafts. RESULTS: Gene transfer of HO-1 grafts
      using an adenoviral vector resulted in the expression of HO-1 protein in
      endothelium and adventitia. We observed that the intimal thickness in Ad-HO-1
      treated aortas (11.11+/-0.92 microm) was significantly thinner compared with
      untreated (85.20+/-6.90 microm) or Ad-null treated (87.20+/-6.20 microm) aortas
      (P<.01). Immunohistology showed that treatment with Ad-HO-1 resulted in a
      significant reduction in leukocyte infiltration and a decreased number of
      vascular smooth muscle cells in the intima, compared with Ad-null-treated aortas.
      The levels of NF-kappaB and the number of apoptotic cells in Ad-HO-1-treated
      aortas showed significantly lower compared with Ad-null-treated arotas (P<.05).
      CONCLUSION: HO-1 prevented the development of graft arteriosclerosis in the rat
      aortic transplant model. The protective role of HO-1 in chronic rejection lesions
      seemed to correlate with downregulation of the expression of NF-kappaB and
      inhibition of apoptosis in the grafts.

PMID- 18089404
TI  - Heme oxygenase-1 protects INF-gamma primed endothelial cells from Jurkat T-cell
      adhesion.
AB  - PURPOSE: The heme oxygenase-1 (HO-1) system is associated with the rate-limiting
      step of conversion of heme, one of the most critical roles in cytoprotective
      mechanisms. Our study investigated its potential role in protection of
      endothelial cells from T cells. METHODS: The recombinant plasmid pcDNA3-HO-1 was
      transfected into endothelial cells. Indirect fluorescent staining was used to
      examine the expression of HO-1 protein. Then endothelial cells primed by INF
      gamma were mixed in culture with Jurkat T cells labeled with carboxyfluorescein
      diacetate succinimidyl ester (CFSE). The number of adhesive Jurkat T cells was
      determined using FACS to evaluate the adhesion effect. After being cultured with
      endothelial cells, the cell cycle of Jurkat T cells was detected using FACS.
      RESULTS: Expression of HO-1 on endothelial cells conferred significant protection
      against Jurkat T-cell-mediated adhesion. The rate of Jurkat T-cell adhesions was
      reduced to 19.06%, in contrast with 31.42% in the control group (P<.05). After
      using ZnPP, an inhibitor of HO-1, the rate of Jurkat T-cell adhesion recovered to
      29.08%. The binding activities between endothelial cells and Jurkat T cells was
      blocked by HO-1 expression. The proliferation of Jurkat T cells was inhibited
      after culture with endothelial cells, which had been transfected with HO-1, which
      blocked cell cycle entry of T cells. More than 60% of Jurkat T cells remained in
      G0/G1 compared with 40% among the control group. CONCLUSION: HO-1 directly
      protected endothelial cells primed by INF-gamma from Jurkat T cells and down
      regulated the expression of HLA-DR on the surface of endothelial cells. These
      results indicated that transgenic expression of HO-1 may be useful to prevent
      lymphocytes from responding to endothelial cells.

PMID- 18089405
TI  - Anti-CD25 mAb, anti-IL2 mAb, and IL2 block tolerance induction through anti-CD154
      mAb and rapamycin in xenogeneic islet transplantation.
AB  - BACKGROUND: We have used anti-CD154 monoclonal antibody (mAb; MR1) and rapamycin
      (rapa) to induce tolerance to islet xenografts. The aim of this study was to
      investigate whether classical anergy and/or regulation by interleukin (IL)2
      dependent CD25+ T regulatory cells played roles in the induction and maintenance
      of tolerance in this model. METHODS: Streptozotocin-induced diabetic mice were
      transplanted with rat islets. We performed the following groups: control group,
      islet transplantation without therapy; rapamycin group, 0.2 mg/kg by oral gavage
      on days 0, 1, 2, and every other day to day 14; anti-CD154 mAb (MR1) group, 0.5
      mg intraperitoneally on days 0, 2, and 4; combination therapy group with rapa and
      MR1. We then administered in addition to the combination therapy with early (from
      days 0 to 14 [for IL2] or to 28 [for anti-IL2 mAb and anti-CD25 mAb] post
      transplantation) or late (from days 100 to 114 [for IL2] or to 128 [for anti-IL2
      mAb and anti-CD25 mAb] posttransplantation) recombinant IL2 (2000 U,
      intraperitoneally twice a day), a neutralizing anti-IL2 mAb (S4B6-1, 0.3 mg
      intraperitoneally twice weekly), and a depleting anti-CD25 mAb (PC61, 0.3 mg
      intraperitoneally twice weekly), respectively. Histology was performed at time of
      rejection. RESULTS: Rapa and MR1 therapy alone significantly prolonged xenograft
      survival compared to the control group: median graft survival was 34 days versus
      17 days (P<.05) and 98 days versus 17 days (P<.05), respectively, but rejection
      still occurred. Combination therapy with MR1 and rapa allowed indefinite graft
      survival (median graft survival [MGS]>200 days, P<.001). When exogenous IL2 was
      administered early with MR1 and rapa, rapid rejection developed in 18 of 18 mice
      (MGS 7 days), whereas when IL2 was given late, only 3 of 10 developed rejection.
      Early administration of anti-IL2 mAb led to rejection in 10 of 10 mice (MGS 42
      days), whereas late administration led to rejection in only one of four mice.
      Early administration of anti-CD25 mAb led to rejection in eight of nine mice (MGS
      49 days), whereas late administration led to rejection in only three of seven
      mice. CONCLUSIONS: Rapa and MR1 allowed indefinite graft survival of islet
      xenografts. Classical anergy and regulation by IL2-dependent CD25+ T regulatory
      cells were critical in the induction of tolerance in the immediate
      posttransplantation period and less important for maintenance of tolerance.

PMID- 18089406
TI  - Anaphylactic reaction after initial exposure of Basiliximab: case reports.
AB  - Basiliximab is potent, relatively safe immunosuppressive induction agent used in
      transplantation. Prophylactic use at the time of transplantation has been
      advocated to improve allograft outcomes. We report two cases of kidney transplant
      recipients with anaphylactic reactions after initial exposure to Basiliximab.

PMID- 18089407
TI  - Single dose of Rituximab plus plasmapheresis in an HIV patient with acute humoral
      kidney transplant rejection: a case report.
AB  - Before the highly active antiretroviral therapy (HAART) era, kidney
      transplantation was not considered an option for patients infected with human
      immunodeficiency virus (HIV) because of its poor outcome. However, recent studies
      have demonstrated results comparable to those of recipients without HIV
      infections. They have shown that HIV-positive patients maintained on HAART mount
      an immune response. Immunosuppressive agents are chosen to minimize aggravation
      of HIV infection, bearing in mind the potential side effects of the combination
      of HAART and immunosuppressive drugs. Herein we have reported the case of a 43
      year-old HIV- and hepatitis C virus-infected woman with preserved immune function
      who received a cadaveric kidney transplant and developed an acute humoral
      rejection, which was successfully treated with Rituximab.

PMID- 18089408
TI  - An unusual presentation of sirolimus associated cough in a renal transplant
      recipient.
AB  - Sirolimus-associated pulmonary problems are rare but life threatening. Pulmonary
      problems due to sirolimus treatment are interstitial pneumonitis, bronchiolitis
      obliterans organizing pneumonia (BOOP), and alveolar hemorrhage. We present a
      case of sirolimus-related cough in the absence of any pulmonary radiological
      findings. A 55-year-old man with a history of 4 years of hemodialysis therapy
      because of end-stage renal disease of unknown etiology underwent cadaveric renal
      transplantation in June 2006. Three days following the initiation of sirolimus
      therapy he complained of dry cough and fever. There were no clinical or
      laboratory findings compatible with specific pulmonary disease. After switching
      sirolimus to tacrolimus, the cough improved within 1-2 days and resolved in 5
      days. Sirolimus should be considered in the differential diagnosis of pulmonary
      problems in the early posttransplantation period even in the absence of
      radiological findings.

PMID- 18089409
TI  - Chronic sensorimotor polyneuropathy associated with tacrolimus immunosuppression
      in renal transplant patients: case reports.
AB  - Tacrolimus is used widely for immunosuppression following transplantation. It has
      rarely been linked to the development of peripheral neuropathy. However, one
      study also reported improvement in peripheral neuropathy after tacrolimus use. We
      have reported herein two patients who developed chronic sensorimotor
      polyneuropathy after tacrolimus use following renal transplantation. One patient
      had an unusual presentation with bilateral facial and extremity weakness and a
      relapsing course. The other patient presented with focal sensory symptoms in one
      hand. Electrophysiological studies confirmed widespread, predominantly
      demyelinating or axonal polyneuropathy. We concluded that patients on tacrolimus
      should be carefully monitored for symptoms suggestive of peripheral neuropathy.

PMID- 18089410
TI  - Decrease in serum tacrolimus level and rise in serum creatinine under late
      addition of cinacalcet in a renal transplant recipient with hyperparathyroidism:
      a case report.
AB  - Cinacalcet is a calcimimetic drug that has been approved for treatment of
      secondary and tertiary hyperparathyroidism in patients with renal failure
      requiring renal replacement therapy. A few cases of successful treatment in renal
      transplant patients immunosuppressed with cyclosporine have been reported. Herein
      we have reported the case of a 48-year-old renal transplant recipient presenting
      with secondary hypercalcemic hyperparathyroidism (parathyroid hormone [PTH] 896
      pg/mL; total calcium, up to 3.3 mmol/L) under immunosuppressive therapy with
      tacrolimus. Owing to substantial comorbidity and a high operative risk, we
      decided to initiate a therapeutic trial with cinacalcet. Using a daily dose of 30
      mg of Cinacalcet, normal calcium levels and a mild fall in PTH levels (decline of
      62 pg/mL) were achieved within the first week of treatment. At this point, we
      also observed a marked decrease in tacrolimus levels (from 6.3 to 2.6 mg/dL)
      without any change in concomitant medications. Thus, we adapted the tacrolimus
      dosage. Concurrent with cinacalcet therapy, there was a rise in serum creatinine
      levels (from 3.9 to 4.9 mg/dL before discontinuation of cinacalcet), which was
      not reversible after termination of 3 weeks of treatment with cinacalcet, but
      continued. Cinacalcet and tacrolimus are both metabolized via cytochrome P 450.
      The documented decrease in tacrolimus serum levels, suggested a drug-drug
      interaction between tacrolimus and cinacalcet. The irreversible deterioration in
      renal function may be attributed to nephrotoxic properties of cinacalcet, but may
      also indicate an acceleration of the natural course of chronic allograft
      nephropathy.

PMID- 18089411
TI  - Isolated primary pulmonary Kaposi's sarcoma in a renal transplant recipient: a
      case report.
AB  - Kaposi's sarcoma (Ks) a relatively common malignancy after kidney
      transplantation, generally presents as characteristic dermatomucosal lesions.
      Visceral organ involvement is common in conjunction with skin lesions; however,
      isolated visceral KS is an uncommon disease among kidney recipients. Isolated
      primary pulmonary KS is a rare finding in this population. Herein we have
      reported on a 38-year-old renal recipient male with respiratory symptoms and a
      normal dermatomucosal examination without lymphadenopathy. Chest imaging revealed
      multiple, bilateral, ill-defined nodular opacities without lymphadenopathy or
      pleural effusion. Pulmonary KS was documented by histopathological evaluation of
      samples obtained from an open lung biopsy. The patient died because of severe
      pneumonia and intra-alveolar hemorrhage. Postmortem evaluation indicated no other
      organ involvement. This case exemplifies the importance of being aware that
      pulmonary KS should not be excluded in the absence of dermatomucosal lesions and
      lymphadenopathy.

PMID- 18089412
TI  - Ureterovesical malignancy following renal transplantation: a case report.
AB  - We present a case of ureterovesical stenosis that developed in 2 of 203 renal
      transplant patients operated between 1997 and 2005 in our department. In the
      current case, an ureterovesical region tumor was identified 1.5 years after renal
      transplantation, while being operated for the correction of ureterovesical
      stenosis. This report sought to remind physicians about the possibility of a
      malignancy in patients with ureterovesical stenosis following renal
      transplantation.

PMID- 18089413
TI  - Donate organs not malignancies: postoperative small cell lung carcinoma in a
      marginal living kidney donor.
AB  - A widening gap between supply and demand for transplantable kidneys has led to
      increasing use of marginal living donors from an elderly population in kidney
      transplantation programs. Although the graft survivals of these marginal organs
      are comparable with those of standard donors, the attendant risk of transmission
      of malignancy from older donors is high, given that aging is a risk factor for
      malignancy. Herein we have highlighted a case of small cell carcinoma developing
      in a marginal elderly donor at 10 months after kidney donation. The recipient
      remains free of malignancy at 36 months after transplantation. The exhaustiveness
      of tests for screening of elderly living donors for malignancy as well as the
      surveillance of recipients at high risk of developing donor-derived malignancy
      remain uncertain.

PMID- 18089414
TI  - Heparin-induced thrombocytopenia type II: a serious hazard in preemptive renal
      transplantation: a case report.
AB  - Heparin-induced thrombocytopenia (HIT) type II (HIT II), is an immune-mediated
      complication of heparin therapy, associated with arterial and venous thrombosis.
      Herein we have reported a case of a 23-year-old woman who developed HIT following
      a living related donor, preemptive, renal transplantation. The patient was
      preoperatively exposed to both unfractionated and low-molecular-weight heparin as
      she underwent five hemodialysis sessions. HIT caused right common and external
      iliac vein and renal graft artery thrombosis, resulting in graft loss. Heparin
      free hemodialysis was continued, and the patient was successfully treated with
      anticoagulation by the direct thrombin inhibitor lepirudin for both the
      thromboses and for hemodialysis. Finally, she was accepted for the continuous
      ambulatory peritoneal dialysis program. This report highlighted the importance of
      clinical awareness as far as previous heparin exposure is concerned for
      establishing an early diagnosis and delivering treatment of this life-threatening
      prothrombotic complication of heparin administration.

PMID- 18089415
TI  - HLA Class II-specific antibodies can react with T cells in flow cytometry
      crossmatch: a case report.
AB  - HLA Class I-specific antibodies are usually detected using a flow cytometry HLA
      crossmatch using T cells. A positive case is shown as a single, right-shifted
      peak on the anti-IgG FITC histogram of T cells. We report a case showing 2 peaks
      occurring concurrently, both positive and negative. The positive peak resulted
      from the binding of HLA Class II-specific antibodies to donor-activated T cells
      expressing the HLA-DR antigens. This case suggested donor-specific HLA Class II
      specific antibodies can bind to some T cells as well as to whole B cells.

PMID- 18089416
TI  - Recurrence of nephrotic proteinuria in children with focal segmental
      glomerulosclerosis after renal transplantation treated with plasmapheresis and
      immunoadsorption: case reports.
AB  - Idiopathic focal segmental glomerulosclerosis (FSGS) is believed to be caused by
      a circulating permeability factor. FSGS recurrence is common after
      transplantation. The treatment is still a matter of debate; plasmapheresis (PE)
      and immunoadsorption (IA) are often used. We report on PE and IA in the treatment
      of two children with recurrent nephrotic proteinuria. Patient 1 was a 16-year-old
      girl who had recurrence of nephrotic proteinuria on the first day after
      transplantation (proteinuria-19 g/d). Primary immunosuppressive therapy was
      changed to high-dose cyclosporine and cyclophosphamide; plasmapheresis was
      started on day 4. Altogether we performed 53 PE and 38 IA procedures. During the
      first month, PE procedures were performed with no more than a 2-day interval
      between sessions, and the girl achieved partial remission (proteinuria 3 g/d). PE
      was then stopped. After 2 months, a relapse of heavy proteinuria occurred. This
      relapse was successfully treated again with intensified PE treatment. After
      achieving remission, a chronic PE regimen was started (PE once a week), similar
      to the previous series. The child remained in partial remission. Seven months
      after renal transplantation, she was switched from PE to IA, because of severe
      hypoproteinemia. Graft biopsy performed at 4 months showed effacement of the foot
      processes. At the present time she has a good graft function and 3 g/d
      proteinuria. Patient 2 was a 13-year-old girl with FSGS since 9 years. On the
      second day after renal transplantation she developed nephrotic proteinuria
      (proteinuria-14 g/d), which was treated with 39 PE and 16 IA treatments. She went
      into complete remission on the intensified PE regimen, had one relapse, and was
      switched to chronic IA. Graft biopsy performed at 2 weeks after transplantation
      showed effacement of the foot processes. At the present time she has good graft
      function and low proteinuria (0.3 g/d). In conclusion, intensified PE or IA
      treatments induced remission of recurrent nephrotic range proteinuria. Chronic PE
      or IA can maintain patients with frequent relapses in long-term remission.

PMID- 18089417
TI  - Successful ABO incompatible living donor liver transplantation in a patient with
      high isoagglutinin titer using high-dose intravenous immunoglobulin.
AB  - The optimal management in living donor liver transplantation using an ABO
      incompatible donor with a high isoagglutinin titer is still uncertain. Our
      patient was a 20-year-old woman with fulminant hepatitis. The only available
      donor was her 54-year-old father-in-law of an incompatible blood type. The
      initial isoagglutinin titer was 2048x. She received 375 mg/m2 of anti-CD20
      antibody 3 days before the living donor liver transplantation with concomitant
      splenectomy. Despite daily plasma exchanges after transplantation, the
      isoagglutinin titer started to shoot up to its maximum value of 2048x, with a
      sudden decline in the bile output. High-dose intravenous immunoglobulin (0.6
      g/kg) was given after the plasma exchanges; thereafter, her liver function tests
      stabilized without a further increase in the isoagglutinin titer. We showed the
      effectiveness of high-dose intravenous immunoglobulin for the management of the
      rebound elevation of isoagglutinin titer. The combination of anti-CD20 antibody
      and daily plasma exchanges seemed ineffective for such a situation. This strategy
      might be another management option for ABO incompatible liver transplantation.

PMID- 18089418
TI  - Cerebellar ataxia in a patient receiving calcineurin inhibitors after living
      donor liver transplantation: a case report.
AB  - Neurological complications of calcineurin inhibitors are frequent problems after
      transplantation. Cerebellar ataxia with other neurological findings and an
      abnormal density area in the subcortical white matter are found by MRI in the
      brains of most patients with central nervous system complications caused by
      calcineurin inhibitors. Such neurological complications are not life-threatening,
      but have a negative impact on the quality of life. We describe a 58-year-old
      woman who developed cerebellar ataxia at 4 days after living donor liver
      transplantation. She walked with a swaying gait, and after walking for 5 minutes
      she was unable to stand. Her symptoms persisted after a change from tacrolimus to
      cyclosporine, but dose reduction of cyclosporine and addition of mycophenolate
      mofetil cured the ataxia. We diagnosed a case of cerebellar ataxia without
      leukoencephalopathy or other neurological symptoms, as a new complication of
      calcineurin inhibitor treatment. We concluded that careful attention should be
      paid to neurological complications of calcineurin inhibitors.

PMID- 18089419
TI  - Interstitial pneumonitis associated with sirolimus in liver transplantation: a
      case report.
AB  - Sirolimus is a powerful immunosuppressive drug initially used in kidney
      transplant patients but now increasingly employed in recipients of other types of
      solid organ transplants, such as liver, heart, lung, or pancreas. Sirolimus is
      indicated for rescue therapy and to reduce the toxic side effects of calcineurin
      inhibitors. However, its use has been associated with an uncommon but important
      pulmonary toxicity. Reports have described interstitial pneumonitis,
      bronchiolitis obliterans, organizing pneumonia, and alveolar proteinosis. We
      present the case of a liver transplant patient with interstitial pneumonitis
      associated with sirolimus.

PMID- 18089420
TI  - Switch to everolimus for sirolimus-induced pneumonitis in a liver transplant
      recipient--not all proliferation signal inhibitors are the same: a case report.
AB  - We report a 62-year-old female liver transplant patient who presented with
      sirolimus (SIR)-related pneumonitis (SIP) treated with a switch to everolimus
      (EVER). At 13-month follow-up, the patient is on EVER monotherapy with no
      recurrence of SIP. Despite common mechanisms of action, the safety profile of
      EVER is different from SIR, and a switch from SIR to EVER should be contemplated
      in cases of SIP to allow patients to benefit from the antifibrotic properties of
      antiproliferative immunosuppressants.

PMID- 18089421
TI  - Intestinal schistosomiasis following orthotopic liver transplantation: a case
      report.
AB  - Recent World Health Organization (WHO) reports estimate that 500-600 million
      people worldwide are at risk of schistosomiasis. In areas of high prevalence of
      hepatitis C (HCV) and schistosomiasis there is an increased risk for end-stage
      liver disease. Liver transplant is a viable option for those with HCV or other
      liver pathology and schistosomiasis. Posttransplant recurrence of schistosomiasis
      has rarely been described. We report a case of posttransplant recurrence of
      schistosomiasis.

PMID- 18089422
TI  - A case of successful resection after long-term medical treatment of invasive
      pulmonary aspergillosis following living donor liver transplantation.
AB  - Invasive pulmonary aspergillosis (IPA) occurs in 1.5 to 10% of liver transplant
      recipients. Of the fungal infections, IPA is the most difficult to treat and the
      most frequently life-threatening. However, the best treatment strategy remains
      controversial. The patient was a 53-year-old woman who underwent living donor
      liver transplantation (LDLT) because of subacute fulminant hepatic failure due to
      autoimmune hepatitis. Aspergillus fumigatus was detected in the sputum taken
      intraoperatively by bronchial suction. A computed tomogram of the lung 7 days
      after LDLT showed fungal balls in the left lung. IPA was diagnosed. Since the
      patient suffered from pulmonary edema postoperatively and fungal balls occupied a
      greater part of the left lung, conservative therapy using micafungin,
      amphotericin B, and itraconazole was first selected. However, the fungus balls
      did not completely disappear. Moreover, brain abscess probably resulting from IPA
      dissemination was detected. Lung resection was performed as reduction surgery,
      and salvage treatment using voriconazole was done for a brain abscess. Septate
      hyphae of Aspergillus fumigatus were identified in the lung specimen. We
      concluded that for patients with IPA after LDLT, pulmonary resection should be
      done as soon as possible before deterioration of IPA and complication due to
      acute cellular rejection.

PMID- 18089423
TI  - Diagnosis and treatment for tuberculosis infection in liver transplant
      recipients: case reports.
AB  - AIM: Tuberculosis (TB) infection after liver transplantation was described,
      diagnosed and treated herein. METHODS: We reviewed the clinical presentation,
      methods of diagnosis, and treatment of 2 cases of TB infection
      posttransplantation. RESULTS: Mycobacterium TB infection occurred in 2 of 110
      (1.8%) patients undergoing liver transplantation between 2001 and 2006. Pyrexia,
      poor appetite, and weight loss were common presentations. The diagnosis was
      confirmed using lymph node biopsy and treated with standard antituberculous
      agents. One patient was suspected of having TB infection by clinical
      presentation, and tentative anti-TB drugs were used. The duration of treatment
      was 9 months. CONCLUSIONS: Early diagnosis and treatment are important in these
      patients. Careful monitoring of liver function and immunosuppressant levels are
      essential for patients who receive standard anti-TB drugs.

PMID- 18089424
TI  - Liver transplantation in the setting of extra-hepatic malignancy: two case
      reports.
AB  - Candidates for liver transplantation (OLT) may be found to have an incidental
      extrahepatic tumor, which is amenable to resection, and may be associated with
      variable long-term survival. Issues to be considered include: (1) Whether it is
      possible to define a tumor stage and survival expectancy, which makes the patient
      an acceptable transplant candidate; (2) Whether cancer surgery should be
      preformed prior, during, or after OLT; (3) Whether the recipient be placed on
      immunosuppression that is tailored to address concern related to cancer
      recurrence. These issues are illustrated in the context of OLT and nephrectomy
      for renal cell carcinoma (RCC). Two patients underwent a simultaneous OLT and
      curative radical nephrectomy for stage 1 RCC that was incidentally discovered
      during OLT evaluation, one of whom received a simultaneous kidney transplant. At
      51 and 14 months postoperatively, the patients are alive and healthy, with no
      tumor recurrence. In selected extrahepatic malignancies, simultaneous curative
      resection and OLT may provide the optimal outcome. This is justifiable when
      curative cancer-related life expectancy exceeds OLT-expected graft and patient
      survival. Concomitant transplantation and cancer surgery provides an acceptable
      cancer-free survival, avoiding the high morbidity observed when cancer resection
      is done in the presence of decompensated liver disease.

PMID- 18089425
TI  - Delayed bile leakage from a remaining part of segment 8 in a posterior section
      graft after living donor liver transplantation: a common pitfall in harvesting a
      posterior section graft? A case report.
AB  - In Japan and Korea, where availability of deceased donor organs for solid organ
      transplantation remains rare, living donor liver transplantation (LDLT) using a
      posterior section graft (PSG; segments VI+VII, according to Couinaud's
      Nomenclature for liver segmentation) has now been accepted as a standard
      procedure that balances donor risk and patient benefits for cases in which right
      hemi-liver donation is too risky, because of marked volume imbalances between
      right and left hemi-livers. Compared with other types of grafts, however, the
      procedure requires detailed knowledge concerning hepatic vascular anatomy and
      meticulous manipulation during donation surgery. We present herein a case of
      delayed bile leakage from a remaining part of segment 8 in a PSG, which was
      considered to be a complication peculiar to LDLT using a PSG.

PMID- 18089426
TI  - Splenic artery steal syndrome in living donor liver transplantation: a case
      report.
AB  - Splenic artery steal syndrome (SASS) has only recently been recognized as a
      potential threat to transplanted livers. We report a case of SASS with
      progressive liver dysfunction that developed after living donor right lobe liver
      transplantation. SASS suspected by serial pre- and postoperative computed
      tomographic (CT) scans was diagnosed by celiac trunk angiography. It was
      successfully salvaged by splenic artery embolization. In this case, serial
      examinations of CT scans were useful to diagnose SASS. This case showed that
      portal hyperperfusion injury is a cause of liver graft dysfunction in SASS. The
      splenic artery embolization technique is a safe procedure that can be applied to
      treat such injury.

PMID- 18089427
TI  - A new biliodigestive anastomosis technique after hepatic artery thrombosis as
      bridge to liver retransplantation: a case presentation.
AB  - Arterial complications after liver transplantation are frequent. Hepatic artery
      thrombosis (HAT) is usually associated with biliary complications. Herein we have
      reported a case of a patient who was admitted for jaundice, itch, and elevated
      aspartate aminotransferase and alanine aminotransferase levels at 6 weeks after
      liver transplantation. HAT associated with a biloma was diagnosed and an urgent
      operation performed requiring a new biliodigestive anastomosis technique.
      Fourteen months after the first transplant, the patient was retransplanted. The
      operation performed may be an alternative to treat biliary complications due to
      late HAT.

PMID- 18089428
TI  - Successful resuscitation of cardiac arrest due to postreperfusion syndrome during
      orthotopic liver transplantation: a case report.
AB  - A patient with alcohol induced end-stage liver disease developed cardiac arrest
      immediately after reperfusion during orthotopic liver transplantation. In our
      case, advanced age of the patient, alcohol-related severe liver disease with high
      ASA score, and myocardial dysfunction, combined with acute metabolic and
      hemodynamic changes throughout the surgery may have contributed to the
      development of postreperfusion syndrome resulting in cardiac arrest. Our patient
      required a total of 5 mg epinephrine, 200 mg lidocaine, 100 mEq NaHCO3, and 40
      mEq calcium gluconate together with direct cardiac compressions and ventilation
      enriched 100% oxygen to regain sinusoidal rhythm. In conclusion, during severe
      postreperfusion syndrome, the collaboration between the surgical and anesthesia
      teams is crucial to overcome cardiac arrest. In an open abdomen, direct cardiac
      compressions through the transdiaphragmatic pericardial window instead of chest
      compressions were important to restore effective circulation during advanced life
      support.

PMID- 18089429
TI  - Malignant hyperthermia in a liver transplant patient: a case report.
AB  - Malignant hyperthermia is an autosomal dominant disorder with incomplete
      penetrance and variable expression. This syndrome is characterized by a
      hypermetabolic response to all commonly used inhalational anesthetics and
      depolarizing muscle relaxants. It can happen during or after the anesthesia. We
      describe a case of malignant hyperthermia during orthotopic liver
      transplantation. Our patient was a 48-year-old man, born in Brazil but with
      European ascendance, who developed malignant hyperthermia associated with the use
      of isoflurane. He was treated with dantrolene, which caused hepatic graft
      dysfunction. It is important that transplant teams be able to recognize and treat
      this complication.

PMID- 18089430
TI  - Extracorporeal shock wave lithotripsy of impacted radiolucent stone at the right
      pyeloureteric junction and oral dissolution therapy in a patient with
      transplanted liver: a case report.
AB  - Extracorporeal shock wave lithotripsy (ESWL) is a safe, effective method to treat
      urinary lithiasis. The success rate in ESWL depends on stone location, size,
      number, and fragility as well as calceal anatomy and patency of the urinary
      tract. An association of calcineurin inhibitors and uric acid urolithiasis has
      been reported in renal allograft recipients, but the mechanism remains unknown.
      Herein we have reported the case of 68-year-old male patient who developed
      cryptogenic cirrhosis and underwent liver transplantation. Seven years after
      transplantation, the patient was admitted to the hospital with right renal colic.
      An 8.9-mm radiolucent stone at the pyeloureteric junction was associated with
      moderate consecutive hydronephrosis. The second stone was located in a lower
      renal calyx. After a failed attempt at retrograde ureteral stenting, we performed
      a percutaneous nephrostomy. Antegrade pyelography with following ESWL treatment
      resulted in disintegration of the obstructive stone at the pyeloureteric
      junction. Afterward, we performed antegrade placement of a double-J stent.
      Residual stones in the lower renal calyx were successfully treated with a 3-month
      course of oral intake of a dissolution agent-potassium sodium hydrogen citrate.
      In this case, we have discussed ESWL and oral dissolution therapy of radiolucent
      stones in a hydronephrotic right kidney, which resulted in stone-free disease
      after 3 months of combined therapy. There was neither clinical nor biochemical
      damage to the transplanted liver.

PMID- 18089431
TI  - Orthotopic liver transplantation in a patient with acute liver failure resulting
      from aortic dissection.
AB  - We report a case of acute liver ischemia resulting in liver failure that occurred
      due to celiac trunk occlusion by an aortic dissection. A 53-year-old patient
      presented with clinical signs of acute abdomen. He underwent an urgent
      laparotomy, which revealed a splenic infarction and thrombosis of the celiac
      artery all the way to the porta hepatis. Imaging showed that an acute
      thoracoabdominal aortic dissection was present, resulting in compression of the
      celiac trunk. The aorta was repaired with an intervascular graft; however, an
      acute insufficiency of the liver ensued, and the patient was urgently
      transplanted. To the best of our knowledge, this is the first report of vascular
      compromise of the liver due to acute aortic dissection that would require liver
      transplantation.

PMID- 18089432
TI  - Heart transplantation in patients with Emery-Dreifuss muscular dystrophy: case
      reports.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is an hereditary syndrome characterized
      by slow but progressive locomotor involvement and cardiomyopathy. Cardiac
      impairment is often the life-limiting feature of the illness. Only a few cases of
      cardiac transplantation have been reported previously in muscular dystrophy, and
      only 4 cases of end-stage disease due to EDMD have been treated previously with
      heart transplantation. Herein we have reported our experince with 2 consecutive
      patients who underwent heart transplantation for EDMD cardiomyopathy.

PMID- 18089433
TI  - Non-Hodgkin's lymphoma, presenting as an isolated endobronchial mass after
      bilateral lung transplantation: a case report.
AB  - BACKGROUND: Lymphoma is a serious complication following solid organ
      transplantation. Endobronchial involvement of non-Hodgkin's lymphoma (NHL) is
      rare usually occurring in the setting of widely disseminated disease. Only a few
      cases of isolated endobronchial NHL have been reported. They were mostly confined
      to the main bronchi. METHODS: Herein we have described a case of an obstructive
      endobronchial NHL lesion in a young patient, which developed 6 years after
      bilateral lung transplantation for cystic fibrosis. RESULTS: Successful treatment
      was obtained with endoscopic resection of the lesion followed by chemotherapy.
      CONCLUSIONS: In rare cases NHL may present as an isolated endobronchial mass in
      the main bronchi. Because in these cases the prognosis seems to be better, early
      diagnosis is essential. Rigid bronchoscopy offers the opportunity to safely
      obtain large amounts of tissue for complete histological diagnosis and to de
      obstruct the airway to relieve the symptoms.

PMID- 18089434
TI  - Vascular anastomosis and two-stage reconstruction of the gut in a living-related
      small bowel transplant recipient: a case report.
AB  - AIM: We sought to discuss vascular anastomosis and gut reconstruction in a living
      related small bowel transplantation recipient. METHODS: Living-related small
      bowel transplantation was performed successfully on a boy with short gut syndrome
      in two stages. In the first stage, 120 cm, of his mother's ileum was implanted
      into the recipient with the artery and vein anastomosed to the recipient's
      sigmoid artery and inferior mesenteric vein, respectively. The two ends of the
      implanted intestine were constructed as stomas. In the second stage,
      reconstruction of the continuity of the digestive tract was performed at 188 days
      after the initial transplantation. The residual small bowel was transected and
      both ends were anastomosed to the proximal and distal end of the graft in end-to
      side fashion. The stomas were closed 30 and 43 days later. RESULTS: Both
      procedures were successful. Postoperative cytomegalovirus infection and acute
      rejection occurred successively and were controlled. No leakage of the
      reconstructed gut or other complications developed after the second procedure.
      The recipient is alive at 15 months with 8 kg an increase in weight. He is caring
      for himself independently and has a half-liquid diet, sometimes supplied with
      auxiliary enteral nutrition. A d-xylose test increased from 4.25% to 25% after
      the small bowel transplantation. CONCLUSIONS: Vascular anastomoses should be
      performed according to the state of graft and the recipient. The portal route is
      the first choice when possible. A two-stage gut reconstruction could decrease the
      incidence of complications, and offer a useful method in living-related small
      bowel transplantation.

PMID- 18089436
TI  - Uremic toxins: what are they? An integrated overview of pathobiology and
      classification.
AB  - Toxic substances, known as uremic toxins, accumulate in body fluids during the
      course of progressive, chronic kidney disease. This article will briefly
      summarize current views on the definition, physico-chemical characteristics,
      pathobiological mechanisms for generation and retention, and cellular
      pathophysiology of uremic toxins. In addition, this article will attempt to
      integrate these disparate phenomena into a systems biology approach as to how
      such toxins lead to the diverse clinical manifestations so characteristic of the
      uremic state.

PMID- 18089437
TI  - Are so-called uremic toxins always toxic?
AB  - OBJECTIVE: Numerous substances qualify as uremic toxins by fulfilling all
      properties characterizing such compounds. However, their role in the development
      of uremic state maybe ambiguous. We followed these properties on the example of N
      methyl-2-pyridone-5-carboxamide (Met2PY) from the nicotinamide end-products
      family. The aim of this study was to determine if these uremic compounds are
      toxic in all circumstances. METHODS: To establish a direct toxic effect, a
      cytotoxicity test was performed. The influence of Met2PY on DNA damage in
      cultured cells was measured, using a comet assay. For in vitro experiments, Moly
      (L5178Y), LLCPK-1, and A549 cell lines were used. We used 250 microM H2O2 and 200
      ng/mL angiotensin II (ANGII) as damaging factors. RESULTS: A direct cytotoxic
      effect of Met2PY on Moly cells was observed. In LLC-PK1 cells, co-incubation with
      0.03 mM Met2PY protected cells against the DNA damage caused by ANG II. In A549
      cells, the action of Met2PY was ambiguous. At lower concentrations (1 and 3 mM),
      it showed protective effects, although 10 mM Met2PY increased the toxic effect of
      250 microM H2O2. CONCLUSIONS: Our results suggest that Met2PY is not always toxic
      or harmful. In some circumstances, it may even express beneficial and protective
      properties.

PMID- 18089438
TI  - Is homocysteine toxic in uremia?
AB  - High levels of homocysteine have been implicated as a cardiovascular risk factor
      in the general population and in patients with chronic renal failure, and
      particularly patients on hemodialysis. To classify a risk factor as causally
      related to a certain disease, both strong epidemiologic data and sound basic
      science studies establishing a mechanism are needed. Among the latter, the
      hypomethylation of proteins and DNA, and protein homocysteinylation, have been
      investigated in uremia, providing for an array of toxic effects in this disease.

PMID- 18089439
TI  - Salt: its role in chronic kidney disease.
AB  - Few controversies in medicine have such a long history as that of whether salt is
      identifiably dangerous or not dangerous. The most common reported association
      between excess dietary salt intake and clinical outcome has been in the field of
      hypertension, but dietary sodium intake mediates effects that go far beyond, and
      are independent of, extracellular fluid expansion and elevation in blood
      pressure. For nephrologists, clinical trials that demonstrate no negative outcome
      of a high salt diet in the general population are thus not particularly
      assuasive, because patients with chronic kidney disease (CKD) represent an entity
      that is by no means comparable to the general population. This review takes a
      look at the challenges associated with salt balance in CKD patients (particularly
      at K/DOQI stage 5), followed by a summary of current concepts believed to play a
      part in salt-mediated pathophysiology, and the conclusion, based on the present
      state of scientific knowledge, that it appears advisable to advocate low dietary
      salt intake in this patient population.

PMID- 18089440
TI  - Phosphate is a uremic toxin.
AB  - Hyperphosphatemia is one of the more prevalent metabolic disturbances in kidney
      failure. Phosphate can be considered a uremic toxin based on the accumulation of
      phosphate during chronic kidney disease, the effects of phosphate on biological
      systems, and the adverse effects of hyperphosphatemia. The renal clearance of
      phosphate is maintained until later stages of chronic kidney disease, when the
      remaining nephrons are no longer able to excrete sufficient phosphate to offset
      dietary phosphate absorption. Clearance of phosphate by conventional forms of
      dialysis is insufficient to prevent hyperphosphatemia in most endstage kidney
      disease patients. Phosphate contributes to metabolic disturbances such as
      hyperparathyroidism, vitamin D resistance, and hypocalemia. In combination with
      these and other factors, hyperphosphatemia damages many organs, including the
      parathyroid glands, bones, and most importantly the cardiovascular system.
      Elevated phosphorus is associated with arterial and valvular calcification,
      arteriosclerosis, and an increased risk of cardiovascular death. Importantly, the
      adverse effects of hyperphosphatemia are partially preventable with the effective
      treatments available today.

PMID- 18089441
TI  - Oxalic Acid as a uremic toxin.
AB  - OBJECTIVE: Oxalic acid (OA) is thought to be a uremic toxin that participates in
      the pathogenesis of uremic syndrome. The objectives of this study were to: (1)
      evaluate the plasma levels of OA in patients with chronic renal disease with
      various levels of glomerular filtration rate and after renal transplantation; (2)
      investigate the salivary secretion of OA and ascorbic acid in healthy subjects
      and in patients with chronic renal failure (CRF); (3) examine the influence of
      water and sodium diuresis and furosemide administration on the urinary excretion
      of OA and ascorbic acid in healthy subjects and in CRF patients without dialysis
      treatment; and (4) evaluate the influence of renal replacement therapy (RRT) on
      secondary hyperoxalemia in hemodialysis patients. DESIGN AND SETTING: This study
      was conducted at the Nephrological Department of P.J. Safarik University. Sixty
      one patients with chronic renal disease, 64 CRF patients, 32 continuous
      ambulatory peritoneal dialysis (CAPD) patients, 15 hemodialysis patients, 21
      patients after renal transplantation, and 15 healthy subjects were examined.
      Maximal water diuresis, diets with low (2 g/day) and high (15 g/day) sodium
      intake, administration of intravenous furosemide (20 mg), and renal replacement
      therapy (CAPD, hemodialysis, hemofiltration, and postdilution hemodiafiltration)
      were utilized in the study. RESULTS: In patients with chronic renal disease and
      those after renal transplantation, direct relationships between plasma OA and
      serum creatinine were found (r = 0.904 and 0.9431, respectively, P < .01).
      Despite a high level of plasma OA in uremic patients (23.1 +/- 10 micromol/L),
      there was no significant difference in salivary OA between control subjects (128
      +/- 19 micromol/L) and CRF patients (135 +/- 24 micromol/L). The urinary
      excretion of OA during maximal water diuresis (from 37.5 to 110.3 micromol/4
      hours) and after intravenous furosemide (from 34.5 to 66.7 micromol/3 hours)
      increased significantly, but was not affected by high intake of NaCl. The most
      significant decrease of plasma OA was observed during postdilution
      hemodiafiltration (63.3%). CONCLUSION: Our study indicates that renal replacement
      therapy is not effective for a permanent reduction of elevated plasma levels of
      OA.

PMID- 18089442
TI  - Intravenous iron, inflammation, and oxidative stress: is iron a friend or an
      enemy of uremic patients?
AB  - Intravenous iron supplementation is a recognized therapy for anemia in chronic
      hemodialysis patients, especially in those treated with erythropoietin. The vast
      majority of patients with chronic kidney disease (CKD) seem to be iron-deficient,
      as evaluated by the usual parameters and by iron staining on bone marrow biopsy,
      because of multiple forms of interference with all phases of iron metabolism. The
      need for iron supplementation in CKD patients becomes obvious. Intravenous iron
      was demonstrated to be superior to oral iron in hemodialysis patients. There is
      also evidence for the superiority of intravenous iron in peritoneal dialysis and
      in nondialysis-dependent CKD patients. On the other hand, intravenous iron could
      promote cytotoxicity and tissue injury, and exacerbate oxidative stress and thus
      endothelial dysfunction, as well as inflammation and the progression of both CKD
      and cardiovascular disease. Nevertheless, correction of anemia is effective in
      reducing oxidative stress and, consequently, cardiovascular risk. The overall
      risk-benefit ratio favors the use of intravenous iron alone or with an
      erythropoietic stimulating agent in the management of renal anemia. Clinical
      judgment is necessary in each individual case to diagnose iron deficiency and
      effectively use intravenous iron.

PMID- 18089443
TI  - High-tone external muscle stimulation in end-stage renal disease: effects on
      symptomatic diabetic and uremic peripheral neuropathy.
AB  - OBJECTIVE AND DESIGN: Pain and peripheral neuropathy are frequent complications
      of end-stage renal disease (ESRD). Because drug treatment is associated with
      numerous side effects and is largely ineffective in many maintenance hemodialysis
      (MHD) patients, nonpharmacologic strategies such as electrotherapy are a
      potential recourse. Among various forms of electrostimulation, high-tone external
      muscle stimulation (HTEMS) is a promising alternative treatment for symptomatic
      diabetic peripheral polyneuropathy (PPN), as demonstrated in a short-term study.
      Based on these novel findings, we performed a prospective, nonrandomized, pilot
      trial in MHD patients to determine (1) whether HTEMS is also effective in
      treating diabetic PPN in the uremic state, and (2) whether uremic PPN is
      similarly modulated. PATIENTS AND INTERVENTIONS: In total, 40 MHD patients
      diagnosed with symptomatic PPN (25 with diabetic and 15 with uremic PPN) were
      enrolled. Both lower extremities were treated intradialytically with HTEMS for 1
      hour, three times a week. Initially, a subgroup of 12 patients was followed for 4
      weeks, and a further 28 patients for 12 weeks. The patients' degree of neuropathy
      was graded at baseline before HTEMS and after 1 and 3 months, respectively. Five
      neuropathic symptoms (tingling, burning, pain, numbness, and numbness in painful
      areas) as well as sleep disturbances were measured, using the 10-point
      Neuropathic Pain Scale of Galer and Jensen (Neurology 48:332-338, 1997). A
      positive response was defined as the improvement of one symptom or more, by at
      least 3 points. Other parameters included blood pressure, heart rate, dry body
      weight, and a routine laboratory investigation. RESULTS: The HTEMS led to a
      significant improvement in all five neuropathic symptoms, and to a significant
      reduction in sleep disturbances for both diabetic and uremic PPN. The response
      was independent of the patient's age, with a responder rate of 73%. The
      improvement of neuropathy was time-dependent, with the best results achieved
      after 3 months of treatment. The HTEMS was well-tolerated by nearly all patients.
      CONCLUSIONS: This pilot study shows for the first time that HTEMS can ameliorate
      the discomfort and pain associated with both diabetic and uremic PPN in MHD
      patients, and could be a valuable supplement in the treatment of pain and
      neuropathic discomfort in patients who do not respond to, or are unable to
      participate in, exercise programs during hemodialysis treatment.

PMID- 18089444
TI  - High prevalence of sleep disorders in hemodialyzed patients requiring
      parathyroidectomy.
AB  - OBJECTIVE: Although there has been contrasting evidence for a causative role of
      parathyroid hormone (PTH) in sleep disorders in patients on maintenance
      hemodialysis, a recent study disclosed the possibility that this role might exist
      at least in patients requiring parathyroidectomy because of failure of medical
      therapy. The present study was devised to assess a possible difference in sleep
      disorders of patients on hemodialysis needing parathyroidectomy and those in whom
      medical therapy controlled hyperparathyroidism. DESIGN AND PATIENTS: To this end,
      a group of 22 patients requiring parathyroidectomy were studied by means of a
      sleep questionnaire, along with a group of 44 patients matched for age, gender,
      body weight, and duration of dialytic treatment. RESULTS: Patients requiring
      parathyroidectomy slept fewer hours (P < .001), had a higher prevalence of sleep
      disorders (P < .001), and were more often insomniac (P < .001). CONCLUSIONS: This
      study indicates that patients on hemodialysis requiring parathyroidectomy for
      intractable hyperparathyroidism comprise a good model for investigating the
      causative role of PTH on disordered sleep, and that these patients have very poor
      sleep. These data support recent findings on the prevalence of sleep disorders in
      dialyzed patients with insuppressible hyperparathyroidism.

PMID- 18089445
TI  - Nicotinamide metabolites accumulate in the tissues of uremic rats.
AB  - OBJECTIVE: N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3
      carboxamide (Met4PY) are nicotinamide (NA) metabolites described by our group and
      considered to be uremic toxins. Plasma concentration of Met2PY and Met4PY in end
      stage renal disease (ESRD) is several-fold higher in comparison with healthy
      controls. However, there are no data about the concentrations of these compounds
      in different tissues. The aim of this study was to establish whether the observed
      high concentrations of these compounds were also present in different tissues of
      uremic animals. METHODS: This study was conducted in 10 5/6 nephrectomized male
      Wistar rats and 10 sham-operated animals. Concentrations of nicotinamide and its
      end products were measured using high-performance liquid chromatography and mass
      spectrometry. RESULTS: We observed significant elevations of Met2PY and Met4PY in
      tissues of uremic rats. The greatest differences between healthy and uremic rats
      were observed in the liver, lungs, and skeletal muscles. Accumulation in the
      kidney and heart was not so pronounced, but in the case of Met4PY was
      statistically significant. CONCLUSIONS: We found that Met2PY and Met4PY
      accumulate not only in the blood but also in tissues of uremic rats.

PMID- 18089446
TI  - Oral sorbent AST-120 increases renal NO synthesis in uremic rats.
AB  - OBJECTIVE: The urine level of nitric oxide (NO) metabolites, i.e.,
      nitrates/nitrites (NOx), in chronic renal failure (CRF) is decreased because of
      reduced renal synthesis of NO. We determined whether the administration of an
      oral sorbent, AST-120, increases the urine level of NOx and the renal expression
      of nitric oxide synthase (NOS) isoforms in CRF rats. METHODS: Chronic renal
      failure rats were produced by 4/5 nephrectomy. Rats were randomized into two
      groups: CRF control rats, and AST-120-treated CRF rats. The AST-120 was
      administered to the rats at a dose of 4 g/kg with powder chow for 16 weeks,
      whereas powder chow alone was administered to control rats. The urine levels of
      NOx were measured by using a NOx colorimetric assay kit. The expression of
      endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) in the
      kidney was determined by immunohistochemistry. Serum and urine levels of indoxyl
      sulfate were determined by high-performance liquid chromatography. RESULTS: Urine
      levels of NOx and the expression of glomerular eNOS and tubulointerstitial nNOS
      were significantly decreased in CRF rats compared with normal rats. The
      administration of AST-120 to CRF rats significantly increased urine levels of NOx
      and the expression of glomerular eNOS and tubulointerstitial nNOS. The
      administration of AST-120 to CRF rats significantly decreased urine and serum
      levels of indoxyl sulfate. CONCLUSIONS: The oral sorbent AST-120 increases NO
      synthesis in the kidneys of uremic rats by increasing the renal expression of
      eNOS and nNOS, through alleviation of indoxyl sulfate overload on the kidney.

PMID- 18089447
TI  - Novel mechanisms in accelerated atherosclerosis in kidney disease.
AB  - OBJECTIVE: Urea undergoes a spontaneous, nonenzymatic transformation to cyanate,
      the active part of which is isocyanic acid, which can cause modifications of a
      variety of proteins in a process called carbamylation. We postulated that, in
      patients with renal disease, the carbamylation of low-density lipoprotein (LDL)
      is a nontraditional risk factor for cardiovascular disease, and that elevated
      urea leads to carbamylated LDL (cLDL), which causes vascular injury and leads to
      atherosclerosis. RESULTS: We showed that carbamylated LDL manifests all of the
      biological effects relevant to atherosclerosis, including endothelial-cell
      injury, the expression of adhesion molecules, and vascular smooth muscle cell
      proliferation. We also developed an enzyme-linked immunosorbent assay to measure
      carbamylated LDL in patients, and showed that cLDL is markedly elevated in
      dialysis patients. CONCLUSIONS: Our data indicate that cLDL may be an important
      nontraditional risk factor for atherosclerosis in patients with kidney disease.

PMID- 18089448
TI  - Inflammation and insulin resistance in uremia.
AB  - Low-grade systemic inflammation is an important potential factor in the
      pathogenesis of insulin resistance in end-stage renal disease (ESRD). Insulin
      resistance and diabetes, characterized by impaired skeletal muscle glucose uptake
      or excess hepatic glucose production, are in turn relevant contributors to
      morbidity and mortality in ESRD patients. Oxidative stress is increased in ESRD,
      in conservative therapy as well as hemodialysis treatment. Recent evidence
      suggests that oxidative stress contributes, at least in part, to both
      inflammation and insulin resistance by modulating the production of
      proinflammatory cytokines and adipokines in monocytes and in adipose tissue. This
      review focuses on the pathogenesis of inflammation and oxidative stress, and the
      effects of their interplay on insulin resistance in ESRD.

PMID- 18089449
TI  - Endogenous secretory receptor for advanced glycation end-products and
      cardiovascular disease in end-stage renal disease.
AB  - The receptor for advanced glycation end-products (RAGE) is involved in
      microvascular and macrovascular complications in diabetes. The expression of RAGE
      is up-regulated in atherosclerotic plaques of diabetic animals, and the
      augmentation of atherosclerosis in diabetic mice is inhibited by the competition
      of RAGE. An endogenous secretory RAGE (esRAGE) was identified as a novel splice
      variant carrying all of the extracellular domains, but devoid of the
      transmembrane and intracytoplasmic domains. The esRAGE is released from the
      cells, to bind advanced glycation end-products, and this is capable of
      neutralizing the actions of advanced glycation end-products on endothelial cells
      in culture. The adenoviral overexpression of esRAGE restores the impairment of
      vascular dysfunction in diabetes, suggesting that esRAGE may be an important
      inhibitor of RAGE signaling in vivo, and may be useful for the prevention of
      diabetic vascular complications. In 203 age-matched and sex-matched type 2
      diabetic and 134 nondiabetic subjects, plasma esRAGE levels were inversely
      associated with carotid or femoral atherosclerosis. In patients with end-stage
      renal disease (ESRD), plasma esRAGE levels are higher than in those without ESRD.
      In a cohort of 206 patients (including 171 nondiabetic patients) with chronic
      renal failure who were followed for a median of 111 months, the cumulative
      incidence of cardiovascular death by Kaplan-Meier estimation was significantly
      higher in subjects in the lowest tertile of plasma esRAGE than in those in the
      middle or highest tertile. Compared with the lowest tertile of plasma esRAGE, the
      hazards ratios for the highest and middle tertile were 0.40 (95% confidence
      interval, 0.18 to 0.89) and 0.26 (95% confidence interval, 0.10 to 0.66),
      respectively. The higher risk at the lower level of esRAGE was still significant
      even after adjustment for body mass index, hypertension, dyslipidemia, and
      vascular complications, and was confounded only by age and diabetes. Thus, we
      postulate that plasma esRAGE is a potential protective factor and a novel
      biomarker against the occurrence of cardiovascular disease in ESRD.

PMID- 18089450
TI  - Relationship between fetuin-A concentration, elevated levels of inflammatory
      markers, and arterial wall stiffness in end-stage kidney disease.
AB  - The risk of cardiovascular mortality is significantly heightened in chronic
      dialysis patients. Aortic wall stiffness, as reflected by aortic pulse-wave
      velocity (PWV), is a strong predictor of cardiovascular events. Loss of the
      aortic wall's elasticity is accelerated in dialysis patients because of
      calcifying medial arteriosclerosis, an active cellular process, controlled by
      calcification inducers and inhibitors. A pivotal role in the inhibition of
      calcium x phosphorus (Ca x P) precipitation is played by fetuin-A, a circulating
      plasma glycoprotein. In hemodialysis patients, lower fetuin-A concentrations were
      associated with increases in both cardiovascular and overall mortality. In our
      own study, a significant negative correlation was established between fetuin-A
      level and aortic PWV in chronic hemodialysis patients. The arterial-stiffening
      process was unaffected by the Ca x P product, but occurred independent of
      elevated interleukin-6 levels.

PMID- 18089451
TI  - Salivary phosphate secretion in chronic kidney disease.
AB  - BACKGROUND: Hyperphosphatemia is an important contributor to cardiovascular
      calcification in chronic renal failure (CRF) patients. Cardiovascular
      calcifications are responsible for the high morbidity and mortality in patients
      undergoing hemodialysis (HD). Despite dietary phosphate reduction and treatment
      with phosphate binders, serum phosphorus level, as recommended by K/DOQI
      guidelines, is achieved only by 50% of dialysis patients. Thus it is necessary to
      identify other therapeutic approaches to reducing serum phosphate. Phosphate may
      be secreted in the saliva, which is then swallowed, and this provides a source of
      endogenous phosphate and thus contributes to the hyperphosphatemia in CRF.
      PATIENTS AND INTERVENTION: This study evaluated salivary phosphate in 68 HD
      patients and 110 subjects with various degrees of CRF, compared with 30 healthy
      subjects. Saxon's test confirmed normal salivary secretion volume in all
      subjects. Salivary and serum phosphate and calcium and serum parathyroid hormone
      were measured. RESULTS: Both HD and CRF patients had significantly higher
      salivary phosphate levels compared with healthy control subjects. In the latter
      group of patients, salivary phosphate correlated positively with serum creatinine
      (P < .0001) and the glomerular filtration rate (P < .0001). CONCLUSIONS: These
      results suggest that the level of salivary phosphate may provide a better marker
      than serum phosphate for the initiation of treatment of hyperphosphatemia in CRF
      and HD patients. The results may also offer a new horizon in the therapy of
      hyperphosphatemia by establishing measures to bind salivary phosphate in the
      mouth, and before saliva is swallowed.

PMID- 18089452
TI  - Effects of sevelamer and calcium-based phosphate binders on mortality in
      hemodialysis patients: results of a randomized clinical trial.
AB  - BACKGROUND: Elevated serum phosphorus and calcium are associated with arterial
      calcification and mortality in dialysis patients. Sevelamer, a phosphate-binding
      polymer, attenuates the progression of arterial calcification; it is unknown
      whether this improves outcomes. PATIENTS AND INTERVENTIONS: A randomized
      comparison of sevelamer and calcium-based phosphate binders was performed in
      hemodialysis patients treated up to 45 months. The primary endpoint was
      mortality. Secondary endpoints included cause-specific mortality and
      hospitalization; 2103 patients were randomized, 2040 received treatment, and 1065
      completed treatment. RESULTS: Overall mortality was not significantly reduced by
      sevelamer (adjusted relative risk = 0.92; 95% confidence interval, 0.78 to 1.09;
      log-rank P = .40). Among patients > or = 65 years of age, sevelamer reduced the
      risk of death (adjusted relative risk = 0.77; 95% confidence interval, 0.62 to
      0.97; log-rank P = .02). Sevelamer patients had a trend toward fewer
      hospitalizations (P = .06) and fewer hospital days (P = .09). CONCLUSIONS: A
      statistically significant reduction in mortality in the overall study population
      was not observed. Sevelamer was associated with a survival benefit among patients
      > or = 65 years of age.

PMID- 18089453
TI  - Depression in patients with chronic renal disease: where are we going?
AB  - Depression is quite prevalent in the end-stage renal disease (ESRD) population,
      with rates as high as 30% in some dialysis centers. There are fewer data on the
      epidemiology of depression in patients with earlier stages of chronic kidney
      disease (CKD), but the disease burden may be just as high. Depression may be
      associated with worse medical outcomes, including increased mortality. Close
      attention to screening and treating depression in all patients may be necessary.
      Several instruments have been used to screen for depression. The most common
      validated depression screening measure in ESRD patients is the Beck Depression
      Inventory. There are limited data on the appropriate therapy for depression in
      CKD patients. Psychotherapy combined with antidepressant medications, such as
      selective serotonin reuptake inhibitors, may be the optimal form of therapy
      (always in close consultation with mental health professionals). Adverse effects
      of antidepressant medications should be considered before prescribing these
      agents, particularly in patients with reduced glomerular filtration rate.
      Additional studies are necessary to further evaluate the optimal methods to
      screen for and treat depression in patients with CKD.

PMID- 18089454
TI  - High prevalence of sleep disorders at the time of CKD diagnosis.
AB  - OBJECTIVE: Sleep disorders are very common in adult and children on maintenance
      hemodialysis and are not cured by renal transplantation. SETTING/DESIGN: Studies
      in our laboratory of patients with a mean plasma creatinine concentration of 2
      mg/dL, studied within 2 months of chronic kidney disease (CKD) diagnosis, have
      detected a high prevalence of sleep disorders that could not be explained by
      using the factors prevalent in hemodialysis patients. MAIN OUTCOME MEASURES: To
      understand if the intrusiveness of the disease is a cause for the high prevalence
      of sleep disorders in early CKD, we have assessed, by means of a questionnaire,
      sleep disorders within 1 month from the diagnosis of renal dysfunction. RESULTS:
      A total of 100 CKD patients with a mean estimated creatinine clearance of 59.1 +/
      26.7 mL/min were studied. The prevalence of sleep disorders was 89%. CONCLUSION:
      We believe this high prevalence might represent the effects of disease's
      intrusiveness and difficulty in coping with the disease.

PMID- 18089455
TI  - Appetite disorders in uremia.
AB  - Patients with chronic kidney disease frequently experience loss of appetite
      (anorexia), which increases in severity during the progression of the disease and
      may lead to protein-energy wasting, morbidity, and mortality. Anorexia represents
      a multiple, complex, and multifactorial disorder that may have its origin in
      renal failure (contemplating not only retention of uremic toxins but also
      peptides and cytokines) but that later on also involves metabolic abnormalities
      not yet corrected by dialysis therapy. This paper reviews current knowledge about
      the clinical signs of uremic anorexia as well as mechanisms involved. Based on
      megestrol acetate interventions and the recent observation that sex may modulate
      uremic appetite behavior, the potential role of sex hormones in treating chronic
      kidney disease anorexia needs to be further explored.

PMID- 18089457
TI  - Sympathetic overactivity in uremia.
AB  - Patients with chronic kidney disease frequently exhibit a sustained overactivity
      of the sympathetic nervous system (SNA) which is caused by neurohormonal
      mechanisms arising in the failing kidney. Additional potential mechanisms
      underlying SNA overactivity include increased levels of angiotensin II and
      asymmetrical dimethylarginine. Overactivity of the SNA contributes to
      hypertension and cardiovascular complications, and it is postulated to be a
      predictor of mortality in the presence of cardiovascular diseases such as
      asymptomatic left-ventricular dysfunction and chronic congestive heart failure.
      The activity of the SNA can be estimated by measurements of plasma and by
      spillover rates of norepinephrine (NE), microneurography (MSNA) in sympathetic
      muscle nerve fibers, and power spectral analysis of heart-rate and blood-pressure
      variability. An increase in SNA, as measured by MSNA, was found in many types of
      human hypertension. The pathogenesis of hypertension in renal failure is complex,
      and arises from the interaction of hemodynamic and neuroendocrine factors. The
      potential effect of erythropoietin treatment on SNA or baroreceptor activity is
      still unclear.

PMID- 18089456
TI  - International study on Sagliker syndrome and uglifying human face appearance in
      severe and late secondary hyperparathyroidism in chronic kidney disease patients.
AB  - OBJECTIVE: It is known that skeletal changes due to secondary hyperparathyroidism
      (SH) can be severe in chronic kidney disease (CKD). Recently described Sagliker
      syndrome (SS) is a very striking and prominent feature of SH in CKD, including an
      uglifying appearance to the face, short stature, extremely severe maxillary and
      mandibulary changes, soft tissue in the mouth, teeth/dental abnormalities,
      fingertip changes, knee and scapula deformities, hearing abnormalities, and
      neurological and, more important, severe psychological problems. DESIGN, SETTING,
      PATIENTS: In the past 8 years, we have encountered 40 cases of SS in SH and CKD
      by performing an international study in Turkey, India, Romania, Egypt, Maleysia,
      Tunis, and China. RESULTS: The medical history of these patients showed that they
      did not receive proper therapy. Changes, particularly in children and teenagers,
      become irreversible, which was disastrous for the patients both aesthetically and
      psychologically. CONCLUSION: Treatment must begin early and be the appropriate
      treatment given in centers with sophisticated skills. Otherwise, the inability to
      correct all the changes in the skull and face, to remodel a new face, to
      extending the height, and, most important, to convince the patients to face the
      dramatic psychological problems can be catastrophic for those patients.

PMID- 18089458
TI  - Altered acetylcholine metabolism of brain in uremia: role of secondary
      hyperparathyroidism.
AB  - OBJECTIVE: Cholinergic system and its neurotransmitter, acetylcholine (ACh), play
      a major role in both behavior and motor function of the nervous system.
      Cholinergic neurons synthesize ACh from choline and acetyl-CoA by choline
      acetyltransferase in the nerve ending. The release of ACh in response to nerve
      impulses is dependent on the intracellular calcium ([Ca2+]i) concentration and
      its gradient. The regulation of a synthesis of ACh after depolarization and ACh
      release is controlled by mass-action effect on choline acetyltransferase
      equilibrium. Behavioral and motor changes in uremia may be due in part to
      derangements in ACh metabolism and such possible abnormalities may be related to
      the state of secondary hyperparathyroidism of chronic renal failure (CRF).
      DESIGN: We studied ACh and choline content, choline release, choline kinase
      activity in brain synaptosomes of CRF with and without secondary
      hyperparathyroidism and in CRF rats treated with verapamil which normalize
      [Ca2+]i in brain synaptosomes of CRF rats. RESULTS: The content of ACh of brain
      synaptosomes increased progressively with the duration of CRF from 3 to 6 weeks.
      ACh and choline release as well as choline uptake were significantly higher in
      CRF rats at all time intervals studied. CONCLUSION: Choline content and the
      activity of choline kinase of brain synaptosomes were deceased after 3 weeks of
      CRF and were significantly lower than in synaptosomes of normal. Normalization of
      ACh and choline content as well as ACh release and the activity of choline kinase
      by parathyroidectomy or treatment with verapamil but these maneuvers did not
      prevent the rise in choline uptake and choline release. Resting levels of
      cytosolic calcium of brain synaptosomes in rats with CRF were significantly
      higher (437 +/- 9 nM) as compared to normal rats (345 +/- 9 nM). This rise in
      [Ca2+]i was prevented either by parathyroidectomy prior induction of CRF or by
      treatment of CRF rats with calcium channel blocker verapamil.

PMID- 18089459
TI  - New approaches for the treatment of genomic damage in end-stage renal disease.
AB  - OBJECTIVE: Patients with end-stage renal disease (ESRD) exhibit an enhanced
      genomic damage which may have pathophysiological relevance for cancer development
      and cardiovascular complications. The DNA damage has been shown both in the pre
      dialysis and dialysis phase by micronucleus (MN) frequency test and single cell
      gel electrophoresis in peripheral blood lymphocytes (PBLs). A major cause of DNA
      damage is oxidative stress, which may be induced by various uremic toxins,
      including advanced glycation end products (AGEs), as well as by activation of the
      renin-angiotensin system. RESULTS: Genomic damage of ESRD patients can be
      ameliorated by daily hemodialysis (DHD), as observed in a cross-sectional study.
      Patients on DHD showed a reduced genomic damage in the MN frequency test in PBLs
      compared to those treated with standard hemodialysis. Another way to decrease DNA
      damage in ESRF seems to be the chronic administration of angiotensin II type 1
      (AT)1 receptor blockers. In 15 maintenance hemodialysis patients, treatment with
      candesartan resulted in a significant improvement of DNA damage. According to our
      in vitro data, these beneficial effects may be a consequence of preventing the
      genotoxic actions of angiotensin II. Vitamin B1 (benfotiamine) was found to be
      able to reduce the amount of circulating AGEs in animal experiments. We could
      show in a pilot study that the application of benfotiamine significantly reduced
      the genomic damage of dialysis patients. CONCLUSION: There are several
      possibilities of lowering genomic damage in dialysis patients, which in the long
      run might lead to lower cancer incidences.

PMID- 18089460
TI  - Effectiveness of antihypertensive treatment in patients with chronic kidney
      disease.
AB  - OBJECTIVE: Hypertension is closely associated with chronic kidney disease (CKD)
      and is one of the main factors of progression of CKD. Early detection of CKD
      allows introducing a therapy that slows the progression of CKD. SETTING: A
      prevalence of hypertension and effectiveness of its treatment were assessed
      during the accomplishment of the Program for Early Detection of CKD in Poland
      (PolNef). RESULTS: In 456 of a total of 2476 participants of PolNef program (269
      females, 187 males), CKD was recognized. Diagnosis of CKD was made according to
      classification proposed by K/DOQI and KDIGO. Estimated glomerular filtration rate
      (eGFR) from serum creatinine, albuminuria and ultrasound examination were the
      main diagnostic tools. Hypertension was defined on the basis of actual
      antihypertensive treatment or on the basis of medium value (> or = 140 and/or >
      or = 90) of three separate measurements of blood pressure. Frequency of
      hypertension and effectiveness of its treatment, frequency of overweight and
      obesity, microalbuminuria, and abnormalities in ultrasound examination of urinary
      system were studied. CONCLUSION: Of the CKD population, 68% were hypertensive,
      21% remained without antihypertensive medication, and 22% on medication were
      effectively treated. Kidney insufficiency with eGFR below 60 ml/min/1.73 m2 was
      recognized in 9% of CKD population. Also, 63% of women and 39% of men without
      hypertension had normal body mass compared to 19% of people with CKD and
      hypertension. Microalbuminuria was found in 51% of women and 66% of men with CKD
      and hypertension. Increased echogenicity of kidney and simple cysts were detected
      significantly more often in hypertensive patients.

PMID- 18089462
TI  - Recombinant human erythropoietin in the treatment of human brain disease: focus
      on cognition.
AB  - Treatment of human brain disease with erythropoietin (EPO) in order to achieve
      neuroprotection and/or neuroregeneration represents a totally new frontier in
      translational neuroscience. Rather than specifically targeting the cause of a
      particular disease entity, EPO nonspecifically influences components of the
      "final common pathway" that determine disease severity and progression in a
      number of entirely different brain diseases. EPO acts in an antiapoptotic, anti
      inflammatory, antioxidant, neurotrophic, angiogenetic, stem cell-modulatory
      fashion. Importantly, it appears to influence neural plasticity. Most likely due
      to these properties, EPO has been found by many investigators to be protective or
      regenerative and to improve cognitive performance in various rodent models of
      neurological and psychiatric disease. The "Gottingen-EPO-stroke trial" has
      provided first promising data on humans for a neuroprotective therapy of an acute
      brain disease. Experimental EPO treatment to improve cognitive function in
      patients with schizophrenia represents a novel neuroregenerative strategy for a
      chronic brain disease. An exploratory trial in chronic progressive multiple
      sclerosis as an example of an inflammatory disease of the nervous system yielded
      first positive results of EPO treatment on both motor function and cognition.
      These promising results are just the beginning and will hopefully stimulate
      further work along these lines.

PMID- 18089461
TI  - Pathogenesis and local drug delivery for prevention of vascular access stenosis.
AB  - A well-functioning vascular access is essential for hemodialysis in end-stage
      kidney disease patients. Synthetic grafts are more prone to the development of
      stenosis than native fistulas. Most of the stenosis is caused by neointimal
      hyperplasia localized at the outflow tract, which is perpetuated by continuous
      stimuli, such as blood flow disturbance, graft material bioincompatibility, and
      repeated needle puncture. Hyperplasia formation is also enhanced by the trauma of
      angioplasty. Recent work suggests that angiogenesis and the migration and
      proliferation of fibroblasts in the adventitia are important for the pathogenesis
      of neointimal hyperplasia. Therefore, the perivascular sustained delivery of
      antiproliferative drugs is a rational approach to inhibit hyperplasia associated
      with hemodialysis grafts. Because of the chronic nature of the stimuli,
      strategies that allow for the ready replenishment of the drug depot are
      preferable and are currently under development.

PMID- 18089463
TI  - Asymmetric dimethylarginine and adiponectin after renal transplantation: role of
      obesity.
AB  - BACKGROUND: In obese renal transplant recipients, we assessed the course of
      selected proinflammatory factors liable to influence long-term outcomes of
      transplant patients and kidney grafts. METHODS: In a prospective cohort study, we
      examined a total of 140 renal transplant recipients for a period of 12 months.
      Based on body mass index (BMI), patients were divided into Group I (BMI > or = 30
      kg/m2, 68 patients) and Group II (BMI < or = 30 kg/m2, 72 patients). RESULTS:
      Twelve months after renal transplantation, significant differences were found
      between Group I versus Group II in plasma levels of asymmetric dimethylarginine
      (ADMA) (3.65 [SD +/- 0.47 micromol/L] versus 2.01 [SD +/- 0.36 micromol/L], P <
      .01), adiponectin (ADPN) (15.4 [SD +/- 6.6 microg/mL] versus 22.3 [SD +/- 8.2
      microg/mL], P < .01), leptin (51.3 [SD +/- 11.2 ng/L] versus 21.3 [SD +/- 9.2
      ng/L], P < .01), soluble leptin receptor (24.6 [SD +/- 8.4 U/mL] versus 46.1 [SD
      +/- 11.4 U/mL], P < .01), resistin (20.8 [SD +/- 10.1 microg/mL] versus 14.6 [SD
      +/- 6.4 microg/mL], P < .025), and triglycerides (3.9 [SD +/- 1.6] versus mmol/L
      2.8 [SD +/- 1.6 mmol/L], P < .01). There were significant correlations between
      ADMA and BMI (r = 0.520; P < .001), and ADPN and BMI (r = -0.570, P < .001). The
      correlation between ADMA and inulin clearance (Cin) was weak (r = -0.185, P <
      .05). CONCLUSIONS: Obesity after renal transplantation is associated with
      increased ADMA and decreased ADPN in plasma, and this may represent a risk factor
      for renal transplant recipients.

PMID- 18089464
TI  - Renal alterations during exercise.
AB  - Proteinuria and hematuria are common during exercise. Proteinuria is usually due
      to glomerular or tubular changes or to an excessive production of protein as in
      myeloma. Certain clinical conditions can, however, result in a functional or
      temporary proteinuria, especially during pregnancy, fever, orthostasis, or
      following physical activity. Sport-related proteinuria following marching,
      exercise, and stress, was first observed in soldiers after long marching.
      Prevalence of proteinuria during exercise ranges from 18% up to 100% depending on
      type of exercise and its intensity. A higher incidence of proteinuria has been
      observed in some sports requiring great exercise intensity and it is certainly
      related to muscular work intensity and would decrease after prolonged training.
      Indeed, exercise-induced proteinuria is strictly related to exercise intensity
      rather than to exercise duration. Exercise aggravates the proteinuria of various
      nephropathies and that of renal transplant recipients. The prevalence of
      hematuria is higher in the athletic than the general population and the main
      difference is that sport-related hematuria resolves spontaneously after physical
      exercise while hematuria found in nonathletic population can be chronic. Sport
      induced hematuria is influenced by exercise duration and intensity. Among the
      mechanisms underlying the exercise induced hematuria are increased body
      temperature, hemolysis, increased production of free radicals, and excessive
      release of catecholamines. Lactic acidosis, generated during anaerobic
      conditions, causes the passage of erythrocytes into the urine, through increased
      glomerular permeability.

PMID- 18089465
TI  - The effect of induced hindlimb lameness on thoracolumbar kinematics during
      treadmill locomotion.
AB  - REASON FOR PERFORMING STUDY: There are no detailed studies describing a
      relationship between hindlimb lameness and altered motion of the back.
      OBJECTIVES: To quantify the effect of induced subtle hindlimb lameness on
      thoracolumbar kinematics in the horse. METHODS: Kinematics of 6 riding horses
      were measured during walk and trot on a treadmill before and during application
      of pressure on the sole of the left hindlimb using a well-established sole
      pressure model. Reflective markers were located at anatomical landmarks on the
      limbs, back, head and neck for kinematic recordings. Ground reaction forces (GRF)
      in individual limbs were calculated from kinematics to detect changes in loading
      of the limbs. RESULTS: When pressure on the sole of the hindlimb was present,
      horses were judged as lame (grade 2 on the AAEP scale 1-5) by an experienced
      clinician. No significant unloading of this limb was found in the group of horses
      (unloading was observed in 4 animals, but was not detectable in the other 2), but
      statistically significant effects on back kinematics were detected. The overall
      flexion-extension (FE) range of motion (ROM) of the vertebral column was
      increased at walk, especially in the thoracic segments. Axial rotation (AR) ROM
      of the pelvis was also increased. At trot, the FE ROM was decreased only in the
      segment L3-L5-S3. During the stance phase of the lame limb, the segment T6-T10
      T13 was more flexed and the neck was lowered at both gaits; the thoracolumbar
      segments were more extended at walk and trot. There were no significant changes
      in the stride length or protraction-retraction angles in any of the limbs.
      CONCLUSIONS: Subtle hindlimb lameness provoked slight but detectable changes in
      thoracolumbar kinematics. The subtle lameness induced in this study resulted in
      hyperextension and increased ROM of the thoracolumbar back, but also in decreased
      ROM of the lumbosacral segment and rotational motion changes of the pelvis.
      POTENTIAL RELEVANCE: Even subtle lameness can result in changes in back
      kinematics, which emphasises the intricate link between limb function and
      thoracolumbar motion. It may be surmised that, when chronically present, subtle
      lameness induces back dysfunction.

PMID- 18089466
TI  - Effect of chiropractic manipulations on the kinematics of back and limbs in
      horses with clinically diagnosed back problems.
AB  - REASON FOR PERFORMING STUDY: Although there is anecdotal evidence of clinical
      effectiveness of chiropractic in treatment of equine back pain, little scientific
      work has been reported on the subject. OBJECTIVES: To quantify the effect of
      chiropractic manipulations on back and limb kinematics in horse locomotion.
      METHODS: Kinematics of 10 Warmblood horses were measured over ground at walk and
      trot at their own, preferred speed before, and one hour and 3 weeks after
      chiropractic treatment that consisted of manipulations of the back, neck and
      pelvic area. Speed was the same during all measurements for each horse. RESULTS:
      Chiropractic manipulations resulted in increased flexion-extension range of
      motion (ROM) (P<0.05) at trot in the vertebral angular segments: T10-T13-T17 (0.3
      degrees ) and T13-T17-L1 (0.8 degrees ) one hour after treatment, but decreased
      ROM after 3 weeks. The angular motion patterns (AMPs) of the same segments showed
      increased flexion at both gaits one hour after treatment (both angles 0.2 degrees
      at walk and 0.3 degrees at trot, P<0.05) and 3 weeks after treatment (1.0 degrees
      and 2.4 degrees at walk and 1.9 degrees and 2.9 degrees at trot, P<0.05). The
      lumbar (L3 and L5) area showed increased flexion after one hour (both angles 0.3
      degrees at walk and 0.4 degrees at trot P<0.05), but increased extension after 3
      weeks (1.4 degrees and 1.2 degrees , at trot only, P<0.05). There were no
      detectable changes in lateral bending AMPs. The inclination of the pelvis was
      reduced at trot one hour (1.6 degrees ) and 3 weeks (3 degrees ) after treatment
      (P<0.05). The mean axial rotation of the pelvis was more symmetrical 3 weeks
      after the treatment at both gaits (P<0.05). There were no changes in limb angles
      at walk and almost no changes at trot. CONCLUSIONS: The main overall effect of
      the chiropractic manipulations was a less extended thoracic back, a reduced
      inclination of the pelvis and improvement of the symmetry of the pelvic motion
      pattern. POTENTIAL RELEVANCE: Chiropractic manipulations elicit slight but
      significant changes in thoracolumbar and pelvic kinematics. Some of the changes
      are likely to be beneficial, but clinical trials with increased numbers of horses
      and longer follow-up are needed.

PMID- 18089467
TI  - Determination of MMP-2 and -9 activities in synovial fluid of horses with
      osteoarthritic and arthritic joint diseases using gelatin zymography and
      immunocapture activity assays.
AB  - REASON FOR PERFORMING STUDY: Matrix metalloproteinases (MMPs)-2 and -9 activities
      have been found elevated in synovial fluid from various joint diseases in man.
      However, in the horse few data are available. OBJECTIVES: To explore the clinical
      significance of MMP-2 and -9 activities in synovial fluid of horses with
      different forms of joint diseases. METHODS: Gelatin zymography and MMP-2 and -9
      immunocapture activity assays were applied on synovial fluids from control joints
      and joints with aseptic joint disease (AJD) and septic arthritis (SA).
      Additionally, MMP-2 and -9 activities were measured in samples from SA to monitor
      the disease process. RESULTS: Zymographic analysis revealed that samples from AJD
      and SA contained significantly increased latent MMP-2 activity compared to
      controls. Samples from SA showed significantly increased monomeric latent MMP-9
      activity compared with all other affected joints and controls. Trace amounts of
      MMP-9 activity, due to the active and dimer form, were detected in samples from
      SA; however, these bands were absent in samples from AJD and controls. Using
      immunocapture activity assays, MMP-2 and -9 activities were found to be
      significantly elevated in joints from SA compared to controls and AJD samples.
      MMP-2 activity in samples from AJD was significantly increased compared to
      controls. Both MMP activities decreased in the joints from SA in the course of
      successful therapy. CONCLUSIONS: Data from zymographic analysis confirmed that
      MMP-2 and -9 were elevated in equine joint diseases. Immunocapture activity
      assays have been shown to be suitable for the quantitative determination of MMP-2
      and -9 activities in synovial fluid of horses. Both MMP-2 and -9 activities seem
      to be useful to indicate SA, and MMP-2 activity might be a suitable marker for
      AJD. POTENTIAL RELEVANCE: These findings encourage the potential use of MMP-2 and
      -9 as additional aids to clinical investigation. Further work is required to
      validate the clinical significance of MMP activities in the progress of different
      joint diseases in horses.

PMID- 18089468
TI  - Ocular penetration of intravenously administered enrofloxacin in the horse.
AB  - REASON FOR PERFORMING STUDY: Information on antibiotic concentrations in the
      equine eye following systemic therapy is limited. Reports that Leptospira spp.
      are frequently present in the eyes of horses with recurrent uveitis, emphasises a
      need for studies on ocular concentrations of specific antibiotics. HYPOTHESES: 1)
      Enrofloxacin, administered i.v. at 7.5 mg/kg bwt q. 24 h, results in aqueous
      humour concentrations greater than the reported minimum inhibitory concentration
      (MIC) for Leptospira pomona. 2) Aqueous humour paracentesis sufficiently disrupts
      the blood-aqueous humour barrier (BAB) to cause an increase in aqueous humour
      protein and enrofloxacin concentrations. METHODS: Aqueous humour enrofloxacin and
      total protein concentrations were determined in 6 healthy, mature horses after
      i.v. administration of enrofloxacin. Paracentesis was performed on the left eye
      on Days 3 and 4, 1 h following enrofloxacin administration, to determine
      enrofloxacin concentrations in healthy eyes and in eyes with mechanical
      disruption of the BAB. Paracentesis was also performed on the right eye 23 h
      after enrofloxacin administration. Blood samples were collected from the horses
      at identical times to determine enrofloxacin aqueous humour:plasma ratios.
      RESULTS: Mean +/- s.d. enrofloxacin concentration in the aqueous humour 1 h post
      administration on Day 3 was 0.32 +/- 0.10 mg/l (range 0.18-0.47); and aqueous
      humour enrofloxacin, total protein and aqueous humour:plasma enrofloxacin ratios
      were higher on Day 4 than Day 3. CONCLUSIONS AND POTENTIAL RELEVANCE: Following
      disruption of the BAB, enrofloxacin concentrations were above the reported MIC
      for Leptospira pomona.

PMID- 18089470
TI  - Ultrasound-guided periarticular injections of the sacroiliac region in horses: a
      cadaveric study.
AB  - REASON FOR PERFORMING STUDY: The traditional techniques for injection of the
      sacroiliac (SI) region are based on external landmarks. Because of the depth of
      the SI joint and pathological modifications, SI injections are sometimes
      challenging in horses. HYPOTHESIS: An ultrasound-guided techniques would allow
      placement of the needle without depending on external landmarks. METHODS:
      Fourteen pelvic specimens were isolated from mature horses. A 20 cm bent spinal
      needle was positioned with ultrasonographic guidance under both iliac wings
      aiming for SI joints using 5 approaches: cranial, craniomedial, medial and 2
      caudal approaches. The length of needle inserted was recorded and 2 ml of latex
      injected. The distance from latex to the closest sacral articular margin, the
      contact between latex and the SI interosseous ligament or the contact with the
      neurovascular structures emerging from the greater sciatic foramen were recorded
      at the time of dissection. RESULTS: Latex was identified under the iliac wing in
      all injections but one. The distance from the latex to the closest sacral
      articular margin was significantly shorter (P = 0.02) for the 2 caudal approaches
      compared to the cranial, craniomedial and medial approaches. Contact between
      latex and the SI interosseous ligament was significantly more frequent (P = 0.01)
      with the cranial, craniomedial and medial approaches (38/73) compared to the
      caudal approaches (1/24). Contact between latex and the neurovascular structures
      was significantly less frequent (P = 0.005) for the cranial and craniomedial
      approaches (0/47) compared to the medial and caudal approaches (8/60). Four
      erratic injections were encountered. CONCLUSIONS: Ultrasonographic guidance
      allowed the needle to engage under the iliac wing without being dependent on
      external landmarks. The caudal approaches allowed deposition of liquid extremely
      close to the SI joint although retroperitoneal injections occurred. CLINICAL
      RELEVANCE: Each approach has advantages/drawbacks that could be favoured for
      selected purposes, but additional work is required to evaluate them on clinical
      cases.

PMID- 18089469
TI  - Prevalence of latent, neuropathogenic equine herpesvirus-1 in the Thoroughbred
      broodmare population of central Kentucky.
AB  - REASON FOR PERFORMING STUDY: An emerging problem of equine herpesvirus-1 (EHV-1)
      infection in horses in the USA is a high-mortality myeloencephalopathy that
      commonly occurs where large numbers of horses are stabled. EHV-1 isolates
      recovered from recent neurological outbreaks represent a mutant virus strain that
      possesses enhanced neuropathogenicity. A central question of EHV-1
      myeloencephalopathy is the latency carriage rate for these mutants of EHV-1 in
      USA horse populations. OBJECTIVE: To estimate the prevalence of neuropathogenic
      strains of EHV-1 as latent infections in the Thoroughbred broodmare population of
      central Kentucky. METHODS: Submandibular lymph nodes (SMLN) were collected during
      post mortem examination of 132 Thoroughbred broodmares. Total DNA purified from
      SMLN tissue was tested for the presence of latent EHV-1 DNA by an ultrasensitive
      magnetic bead-based, sequence-capture, nested PCR method. Differentiation of
      active from latent infections by EHV-1 was achieved by detection of transcripts
      of EHV-1 glycoprotein B by reverse transcription PCR. RESULTS: Latent EHV-1 DNA
      was detected in the SMLN tissues of 71 (54%) of the 132 mares submitted for
      necropsy. Thirteen (18%) of the 71 latently infected horses harboured the
      neuropathogenic biovar of EHV-1. Of the 13 horses latently infected with an ORF30
      mutant strain of EHV-1, 11 also carried a latent, wild-type strain of the virus
      in their SMLN tissues. CONCLUSIONS: Neuropathogenic strains of EHV-1 have
      established a significant presence in the Thoroughbred broodmare population of
      central Kentucky as latently infected carrier horses. The data also indicate that
      a highly sensitive DNA detection method is required to identify many instances of
      EHV-1 latency. POTENTIAL RELEVANCE: The presence of a relatively large biological
      reservoir of latent, neuropathogenic EHV-1 has the potential for posing emerging
      equine health and economic threats to the future prosperity of the USA horse
      industry.

PMID- 18089471
TI  - An epidemiological study of myopathies in Warmblood horses.
AB  - REASON FOR PERFORMING STUDY: There are few detailed reports describing muscular
      disorders in Warmblood horses. OBJECTIVES: To determine the types of muscular
      disorders that occur in Warmblood horses, along with presenting clinical signs,
      associated risk factors and response to diet and exercise recommendations, and to
      compare these characteristics between horses diagnosed with polysaccharide
      storage myopathy (PSSM), those diagnosed with a neuromuscular disorder other than
      PSSM (non-PSSM) and control horses. METHODS: Subject details, muscle biopsy
      diagnosis and clinical history were compiled for Warmblood horses identified from
      records of biopsy submissions to the University of Minnesota Neuromuscular
      Diagnostic Laboratory. A standardised questionnaire was answered by owners at
      least 6 months after receiving the muscle biopsy report for an affected and a
      control horse. RESULTS: Polysaccharide storage myopathy (72/132 horses) was the
      most common myopathy identified followed by recurrent exertional rhabdomyolysis
      (RER) (7/132), neurogenic or myogenic atrophy (7/132), and nonspecific myopathic
      changes (14/132). Thirty-two biopsies were normal. Gait abnormality, 'tying-up',
      Shivers, muscle fasciculations and atrophy were common presenting clinical signs.
      Forty-five owners completed questionnaires. There were no differences in sex,
      age, breed, history or management between control, PSSM and non-PSSM horses.
      Owners that provided the recommended low starch fat supplemented diet and regular
      daily exercise reported improvement in clinical signs in 68% (19/28) of horses
      with a biopsy submission and 71% of horses diagnosed with PSSM (15/21).
      CONCLUSIONS: Muscle biopsy evaluation was a valuable tool to identify a variety
      of myopathies in Warmblood breeds including PSSM and RER. These myopathies often
      presented as gait abnormalities or overt exertional rhabdomyolysis and both a low
      starch fat supplemented diet and regular exercise appeared to be important in
      their successful management. POTENTIAL RELEVANCE: Warmbloods are affected by a
      variety of muscle disorders, which, following muscle biopsy diagnosis can be
      improved through changes in diet and exercise regimes.

PMID- 18089472
TI  - Post mortem survey of dental disorders in 349 donkeys from an aged population
      (2005-2006). Part 2: epidemiological studies.
AB  - REASON FOR PERFORMING STUDY: Dental disorders have recently been recognised as
      having major clinical and welfare implications in donkeys. However, no
      investigation appears to have examined the association of dental disorders with
      managemental factors and any intercurrent illness. OBJECTIVES: To determine the
      association of dental disorders observed in a post mortem study with age group,
      body condition score, time since last dental treatment, feeding and the illness
      that necessitated euthanasia or caused death. METHODS: A prospective study
      documented the type and prevalence of dental disorders in 349 mainly aged donkeys
      (median estimated age of 31 years) that were subjected to euthanasia over an 18
      month period in 2005'Ai2006. The estimated age, body condition score,
      supplemental feed status, time since last dental treatment and nature of the
      intercurrent disease that necessitated euthanasia or caused death were also
      recorded. Multivariable analysis was performed to examine associations of these
      factors with specific dental disorders and between specific dental disorders.
      RESULTS: There was a high prevalence (93.4%) of significant dental disease. Age
      group was significantly associated with the presence of dental disorders and an
      older age range was a high risk factor for the presence of cheek teeth (CT)
      diastemata. There was a significant association between the presence of CT
      diastemata and the concurrent presence of displaced, missing and worn CT. There
      was also a significant association between the presence of diastemata and colic.
      CONCLUSIONS AND POTENTIAL RELEVANCE: Aged donkeys have a high prevalence of
      dental disorders especially of CT diastemata. Dental disorders and, in
      particular, the presence of CT diastemata were significantly associated with
      colic. Routine, prophylactic dental treatments should be performed, especially in
      aged donkeys.

PMID- 18089473
TI  - Polyneuropathy of Finnish horses characterised by inflammatory demyelination and
      intracisternal Schwann cell inclusions.
AB  - REASON FOR PERFORMING STUDY: A neurological disorder characterised by pelvic limb
      metatarsophalangeal joint extensor paresis has been observed in numerous horses
      in Scandinavia for the last decade. Very little has been formally reported and
      there have been no detailed assessments of the neurological signs or
      neuropathological lesions. OBJECTIVES: To describe the epidemiological and
      pathological features of an outbreak of 'Scandinavian knuckling syndrome' in a
      riding stable in southern Finland. METHODS: Clinical neurological examination of
      4 cases and neuropathological assessment of tissues of one case were performed.
      RESULTS: Eleven out of 17 horses fed on ryegrass from a common source showed
      progressive clinical signs of metatarsophalangeal extensor paresis necessitating
      euthanasia of 7 horses. Nervous system lesions in one horse consisted of a novel
      demyelinating, mildly inflammatory peripheral neuropathy, with BiP/GRP positive
      rough endoplasmatic reticulum Schwann cell inclusions. CONCLUSIONS: The clinical
      signs and lesions documented differ from any previously described equine
      polyneuropathy and suggest a primary Schwann cell lesion. POTENTIAL RELEVANCE:
      The classification of this disease as a novel demyelinating polyneuropathy may
      assist focused epidemiological investigations.

PMID- 18089474
TI  - Arthroscopic injection of corticosteroids into the fibrous tissue of subchondral
      cystic lesions of the medial femoral condyle in horses: a retrospective study of
      52 cases (2001-2006).
AB  - REASONS FOR PERFORMING STUDY: There are no published results of subchondral
      cystic lesions (SCLs) in the medial femoral condyle (MFC) treated with
      arthroscopic injection of corticosteroids into the lining of the cyst.
      OBJECTIVES: 1) To determine the success rate for treatment of SCLs in the MFC
      with arthroscopic injection of the fibrous tissue of the cyst with
      corticosteroids. 2) To identify any factors that may predict outcome. HYPOTHESES:
      Injection of the fibrous tissue of SCLs of the MFC with corticosteroids utilising
      arthroscopic guidance yields a similar or higher chance for intended performance
      than does arthroscopic debridement as previously reported; this technique will be
      effective for treating SCLs in older horses. METHODS: Horses with clinical and
      radiographic evidence of a SCL in the MFC were injected with corticosteroids
      under arthroscopic guidance, and case records and radiographs were reviewed
      retrospectively. A telephone survey of referring veterinarians, owners and
      trainers was conducted. RESULTS: Thirty-five of 52 (67%) cases were classified as
      successful involving 73 SCLs of which 56 (77%) were classified as successful.
      There was no significant association between age group (age<or=3 years vs. >3
      years) and outcome, or cyst configuration and outcome. Significantly more
      unilateral SCLs (28/31 [90%] SCLs) were classified as successful than bilateral
      (28/42: 67%). There were significant differences in outcome based on the surgeon
      operating the case and an association between pre-existing radiographic findings
      of osteophytes and negative outcome. CONCLUSIONS: Injection of SCLs utilising
      arthroscopic guidance is an effective alternative method of surgical treatment of
      SCL. POTENTIAL RELEVANCE: This technique offers a similar chance of success as
      has been reported with debridement and may allow for a shorter period of
      convalescence. If unsuccessful, the option remains to debride the cyst in a
      second surgery.

PMID- 18089476
TI  - [The past and present of peritoneal dialysis].
AB  - The author reviews briefly the history of peritoneal dialysis, and highlights the
      significance of the work of two Hungarian nephrologists, Stephen I. Vas and
      Istvan Taraba . By now, peritoneal dialysis has been considered as equal renal
      replacement modality compared to haemodialysis. It is even more advantageous in
      the protection of the patients' residual renal function, morbidity-mortality
      indices, and quality of life peritoneal dialysis in the first two years. From
      economical point of view peritoneal dialysis is less expensive than hemodialysis,
      therefore in the future its greater role can be expected in the treatment of more
      and more renal patients. The recently achieved technical development, and also
      the more widespread use of the automated peritoneal dialysis machines contribute
      to quality improvement. The peritoneal dialysis therapy, by the patients' self
      treatment, establishes a new kind of relationship between the patients and the
      medical personnel; there is a growing requirement for patient education, the
      patients' self-esteem and cooperation increase, which altogether provides better
      results in rehabilitation and higher quality of life. Our national peritoneal
      dialysis utilization falls behind the European achievements, but has been growing
      dynamically, and we can expect an increase of the number of renal patients on
      peritoneal dialysis.

PMID- 18089477
TI  - [The role of imaging methods in the pre- and intra-operative evaluation, and in
      post-operative follow-up of living donors in liver transplantation in Hungary].
AB  - The evaluation protocol for liver donors can vary from centre to centre, but the
      main points are the same. Medical history, physical examination, common
      laboratory tests and psychosocial evaluation are followed by imaging, and
      specific haemostasis and viral serology tests. The first imaging examinations
      have the aim of excluding any disease; conventional chest radiography and
      abdominal ultrasound are performed. Liver volume, fat content, and vascular and
      biliary anatomy are then evaluated with contrast-enhanced, multiphase,
      multidetector row CT/CTA and MR cholangiography. Ultrasound guided liver biopsy,
      and in some cases digital subtraction angiography, should also be performed.
      During the first phase of the donor operation, intraoperative investigations are
      done: cholangiography for the final evaluation of the biliary tree and ultrasound
      of the hepatic and portal venous system to help draw the resection plane. Donors
      have regular imaging examinations in the early postoperative period for early
      detection of complications: mainly US or CT to check the remnant hepatic
      vascularisation and fluid collections in the operated area, or X-ray for thoracic
      disorders. It is recommended that regular checkups are performed in the late
      postoperative period. The paper describes the imaging protocol for donor
      evaluation applied at our institute at the beginning of our living related liver
      transplantation programme.

PMID- 18089478
TI  - [The prevention of the hypertension related damage in type-2 diabetes: the first
      step of the ADVANCE trial].
AB  - ADVANCE (Action in Diabetes and Vascular disease: preterAx and diamicroN-MR
      Controlled Evaluation) is a large-scale trial designed to investigate the
      benefits of blood pressure lowering and intensive glucose control in patients
      with type 2 diabetes. After a mean of 4.3 years of follow-up, 73% of those
      assigned to active treatment (fix combination of 4/1.25 mg
      perindopril/indapamide) and 74% of those assigned to control remained on
      randomised treatment. Compared with patients assigned to placebo, those assigned
      to active therapy had a mean reduction in blood pressure of 5.6/2.2 mm Hg. The
      relative risk of a major macrovascular or microvascular event was reduced by 9%
      (861 [15.5%] active vs 938 [16.8%] placebo; hazard ratio 0.91, 95% CI 0.83-1.00,
      p = 0.04). The fix combination of perindopril and indapamide could be the best
      possible protector against hypertension-related consequences for patients with
      type 2 diabetes mellitus.

PMID- 18089479
TI  - [Craniospinal malformations in a twelve-year fetopathological study; the
      efficiency of ultrasonography in view of fetopathological investigations].
AB  - BACKGROUND: Craniospinal malformations represent a heterogeneous group of
      congenital malformations by their morphology and etiology alike. Certain
      craniospinal malformations could be diagnosed as early as the dawn of
      ultrasonography and this group of malformations has been the focus of attention
      ever since. AIMS: The aim of the authors was to review the main characteristics
      of craniospinal malformations, as well as to evaluate the efficiency of
      ultrasonography based on autopsy examinations during twelve years. STUDY DESIGN:
      The current study comprises the details of 339 pregnancies terminated by induced
      abortion for craniospinal malformation between 1995 and 2006. RESULTS: Maternal
      median age was 27 +/- 5.8 years, ranging from 15 to 47 years. In 24.5% of the
      cases, there was a positive obstetrical-gynaecological or genetic history. In
      68.1% of the cases, ultrasonographic and autopsy findings were completely
      identical; in 24.2% a partial coincidence was found, but autopsy allowed for
      further diagnoses, while in 26 cases (7.7%) different findings were obtained by
      prenatal ultrasonography and fetopathological investigations. In half of the
      latter 26 cases, induced abortion was suggested due to hydrocephalus confirmed by
      ultrasonography but not justified by autopsy or the autopsy revealed the presence
      of other craniospinal malformation(s). CONCLUSION: It can be concluded that--in
      view of the diagnostic efficiency of fetopathological investigations--the
      ultrasonographic diagnosis of hydrocephalus should be interpreted independently
      from other craniospinal malformations on the basis of principles of
      ultrasonographic methodology and at different times.

PMID- 18089480
TI  - [Vena cava superior syndrome: surgical treatment of the thrombosis of the
      superior vena cava after implantation of a hemodialysis catheter--a case report
      and review of the literature].
AB  - One of the rare reasons of the non malignant superior vena cava syndrome is the
      thrombosis of superior vena cava. Obstruction or occlusion of central veins is
      one of the many complications of the more and more frequently used central venous
      catheters and pacemaker electrodes. The authors report a case of superior vena
      cava thrombosis resulting in dialysis catheter insufficiency in case of a young,
      uraemic, female patient wit Tesio catheter and the surgical treatment of it with
      the use of cardiopulmonary bypass during the operation. Apropos of this case, the
      authors outline the causes of malignant, non-malignant and iatrogenic superior
      vena cava syndrome, furthermore the conservative, surgical and catheter therapy
      of the syndrome.

PMID- 18089481
TI  - [Jellyfish sting. A case report].
AB  - Jellyfish bites in Hungary are rare. Yet, from a differential diagnostic point of
      view this epizoonozis might gain importance given the ever-growing popularity of
      seaside tourism. A 10 year old female patient was stung by a jellyfish while sea
      bathing in the Adriatic in the summer of 2005. A couple of minutes after the bite
      urticaria were formed in the contacted area accompanied by a burning and sore
      sensation. In a few hours the above lesions turned livid and the patient
      developed low-grade fever and general discomfort. In acute therapy she received
      thorough rinse with vinegar, antibiotic ointment and systemic calcium. General
      symptoms regressed within 24 hours and dermatological symptoms improved
      progressively. Finally, the patient grew symptomless in 4 weeks altogether due to
      general antihistamine and local antibiotic therapy. 3 months later the patient
      presented again with hyperaemic papules and an increasing itching and burning
      sensation in the previously jellyfish-contacted area. Histopathology showed
      vascular involvement and eosinophilic infiltration. The inflammatory symptoms
      gradually diminished to locally applied steroids in an occlusive bandage leaving
      behind hypopigmentation. Although bare-skin contact with the different poisonous
      jellyfish species usually do lead to the forming of dermatological symptoms,
      vascular involvement developed months after the encounter in the exposure site
      has seldom been published. The article covers the main potential symptoms of
      jellyfish stings--both local and general--going into details about the possible
      dermatological differential diagnoses. Furthermore, the most venomous jellyfish
      species, their geographical habitats, do's and don't-s of first aid, therapy and
      prevention are being briefly discussed by the authors.

PMID- 18089485
TI  - Recommendations for the reporting of surgically resected specimens of colorectal
      carcinoma: Association of Directors of Anatomic and Surgical Pathology.

PMID- 18089486
TI  - Recommendations for the reporting of prostate carcinoma: Association of Directors
      of Anatomic and Surgical Pathology.

PMID- 18089487
TI  - Evaluation of a multiplex fluorescent microsphere immunoassay for the
      determination of epstein-barr virus serologic status.
AB  - Epstein-Barr virus (EBV), a human herpesvirus, affects up to 95% of adults.
      Diagnosis of acute EBV infection can be challenging and often relies on the
      serologic antibody pattern to 3 distinct antigens, most often determined by
      indirect fluorescent antibody (IFA), enzyme-linked immunosorbent assays (ELISAs),
      and, more recently, multiplex assays. We compared a multiplex assay for the
      simultaneous detection of antibodies to viral capsid (VCA), nuclear (EBNA), and
      early (EA) EBV antigens with ELISAs using IFA for discrepancy resolution.
      Concordance of the multiplex assay was good for all 4 antigens: VCA IgM, 86.6% vs
      ELISA and 92.9% vs IFA; VCA IgG, 92.8% vs ELISA and 98.0% vs IFA; EBNA IgG, 90.3%
      vs ELISA and 98.1% vs IFA; and EA IgG, 83.8% vs ELISA and 92.8% vs IFA. After IFA
      resolution, correlation between the multiplex assay and ELISA for serologic
      disease stage, based on the antibody profile of all 4 analytes, was 90%. The
      multiplex assay showed good correlation with an established ELISA and even better
      correlation with the "gold standard" IFA. Advantages of the multiplex assay over
      traditional methods include multiple results per assay, inclusion of internal
      controls for each assay, and well-to-well monitoring of assay drift.

PMID- 18089488
TI  - Antigen-specific ANCA ELISAs have different sensitivities for active and treated
      vasculitis and for nonvasculitic disease.
AB  - This study evaluated the performance of 12 assays for antineutrophil cytoplasmic
      antibodies (ANCA) directed against proteinase 3 (PR3) and myeloperoxidase (MPO)
      in 55 active and 68 treated cases of vasculitis and in nonvasculitic disease. It
      examined within- and between-assay precision; binding curves, binding levels, and
      interassay consistency; and sensitivity, specificity, and receiver operating
      characteristic analysis. All assays were highly sensitive for active vasculitis
      (median, 94%; range, 91%-96%), but sensitivities were more varied in treated
      disease (median, 69%; range, 57%-82%). Binding curves and binding levels were
      also very variable in PR3-ANCA and MPO-ANCA assays. This has implications for
      studies correlating ANCA levels with disease activity and in developing ANCA
      based treatment guidelines. PR3-ANCA and MPO-ANCA assays need to be standardized
      as a matter of urgency, but in the meantime, individual laboratories must
      understand the limitations of the assays used, especially with low-level ANCA in
      treated vasculitis and nonvasculitic disease.

PMID- 18089489
TI  - Mitochondrial genome deletion aids in the identification of false- and true
      negative prostate needle core biopsy specimens.
AB  - We report the usefulness of a 3.4-kb mitochondrial genome deletion (3.4 mtdelta)
      for molecular definition of benign, malignant, and proximal to malignant (PTM)
      prostate needle biopsy specimens. The 3.4 mtdelta was identified through long
      extension polymerase chain reaction (PCR) analysis of frozen prostate cancer
      samples. A quantitative PCR assay was developed to measure the levels of the 3.4
      mtdelta in clinical samples. For normalization, amplifications of a nuclear
      target and total mitochondrial DNA were included. Cycle threshold data from these
      targets were used to calculate a score for each biopsy sample. In a pilot study
      of 38 benign, 29 malignant, and 41 PTM biopsy specimens, the difference between
      benign and malignant core biopsy specimens was well differentiated (P & .0001),
      with PTM indistinguishable from malignant samples (P = .833). Results of a larger
      study were identical. In comparison with histopathologic examination for benign
      and malignant samples, the sensitivity and specificity were 80% and 71%,
      respectively, and the area under a receiver operating characteristic (ROC) curve
      was 0.83 for the deletion. In a blinded external validation study, the
      sensitivity and specificity were 83% and 79%, and the area under the ROC curve
      was 0.87. The 3.4 mtdelta may be useful in defining malignant, benign, and PTM
      prostate tissues.

PMID- 18089490
TI  - The use of fine needle aspiration cytology for the distinction of pancreatic
      mucinous neoplasia.
AB  - Cytology frequently has some role in preoperatively distinguishing pancreatic
      mucus-producing neoplasia (intraductal papillary mucinous neoplasms [IPMNs] and
      mucinous cystic neoplasms [MCNs]) from other pancreatic cysts. We evaluated all
      cytologic specimens at our institutions from resected pancreatic cystic lesions
      for lesional extracellular and cellular material. Lesional extracellular material
      was identified in 32 of 38 of the cytologic samples from cystic pancreatic mucus
      producing neoplasms (28 of 31 IPMNs and 4 of 7 MCNs). Lesional cellular material
      was seen in 22 of 38 cases (17 of 31 IPMNs and 5 of 7 MCNs). Lesional material
      was more commonly identified in higher grade and invasive lesions. Lesional
      extracellular material was seen in 3 of 14 samples of other pancreatic cysts, and
      lesional cellular material was seen in 6 of 14 cases.

PMID- 18089491
TI  - The risk of false-positive histology according to the reason for colposcopy
      referral in cervical cancer screening: a blind revision of all histologic lesions
      found in the NTCC trial.
AB  - All cervical intraepithelial neoplasia (CIN) diagnoses identified during the New
      Technologies for Cervical Cancer trial (ISRCTN81678807) were blindly reviewed by
      2 pathologists. Original diagnoses based on colposcopy-guided biopsies were
      compared with those made by the reviewers who had access to all clinical
      histologic samples (including postsurgical). Cases downgraded from CIN 2+ by the
      reviewers were considered indicative of unnecessary treatments. The analyses are
      presented according to the molecular (high-risk human papillomavirus [HPV])
      and/or cytologic diagnosis used to refer the women for colposcopy. We reviewed
      812 CIN 1 and 364 CIN 2 + diagnoses. The specificity of colposcopy-guided biopsy
      was 98% and the sensitivity, 84%. The probability of unnecessary treatment was
      27% for women with atypical squamous cells of undetermined significance cytologic
      findings and 8% for women with low-grade squamous intraepithelial lesion or
      worse, 10% for HPV+ and positive cytologic findings, and 16% for HPV+ alone. The
      positive predictive value of the first-level screening test was inversely
      associated with probability of a histologic false-positive result (P = .015). In
      screening, a low positive predictive value of the colposcopy-referring test may
      result in unnecessary treatments.

PMID- 18089492
TI  - Usefulness of S100P in diagnosis of adenocarcinoma of pancreas on fine-needle
      aspiration biopsy specimens.
AB  - Even though the cytologic criteria for pancreatic ductal adenocarcinoma (PDA) on
      fine-needle aspiration biopsy (FNAB) specimens have been well defined, a
      diagnostic challenge is still present. We immunohistochemically evaluated the
      diagnostic value of S100P on cell-block and/or smear preparations in 58 cases of
      FNAB specimens of the pancreas. The 58 cases were divided into 4 groups: 1, 32
      cases of PDA; 2, 6 cases with an atypical or "suspicious" diagnosis; 3, 14 cases
      of benign or reactive ductal epithelium; and 4, 6 cases of endocrine tumor.
      Positive immunoreactivity for S100P was observed in all cases in groups 1 and 2,
      whereas only 1 of 14 cases in group 3 was positive for S100P. All cases in group
      4 were negative for S100P. S100P is a sensitive and specific marker for the
      detection of PDA on FNAB specimens on cell-block and smear preparations.

PMID- 18089493
TI  - Detection of Helicobacter pylori gastritis by PCR: correlation with inflammation
      scores and immunohistochemical and CLOtest findings.
AB  - We developed a polymerase chain reaction (PCR) assay to detect Helicobacter
      pylori in gastric and/or gastroesophageal biopsy specimens of adults with
      dyspepsia, compared the method with immunohistochemical analysis and CLOtest
      (Ballard Medical Products, Draper, UT), and correlated the results of each test
      with the histologic features of infection. H pylori was identified in 36 (60%) of
      60 patients irrespective of biopsy site and testing method. In the gastric biopsy
      specimens, PCR detected H pylori in 29 (52%) of 56 cases, including 11 (100%) of
      11 immunohistochemically and/or CLOtest-positive cases. PCR-positive gastric
      biopsy specimens correlated with a higher average cumulative inflammatory score
      compared with PCR-negative specimens (P = .001). In gastroesophageal biopsy
      specimens, PCR detected H pylori in 15 (34%) of 44 cases, including 1 (20%) of 5
      immunohistochemically positive specimens. PCR-positive gastroesophageal junction
      biopsy specimens did not correlate with a higher average cumulative inflammatory
      score. Overall, PCR detected an additional 23 cases negative by
      immunohistochemical analysis and/or CLOtest. This PCR assay identified a
      significant number of H pylori infections that would not be detected by
      immunohistochemical analysis and/or CLOtest.

PMID- 18089494
TI  - Using the rate of positive high-risk HPV test results for ASC-US together with
      the ASC-US/SIL ratio in evaluating the performance of cytopathologists.
AB  - We reviewed our experience with 2 indicators of cytopathologist performance: the
      relative frequency of the interpretations atypical squamous cells of undetermined
      significance (ASC-US) and squamous intraepithelial lesion (SIL) and the frequency
      of positive test results for high-risk human papillomavirus (HR-HPV) DNA
      associated with a cytologic interpretation of ASC-US. Data derived for 9
      cytopathologists were reviewed. ASC-US/SIL ranged from 0.99 to 4.02 (mean, 1.77)
      in 2005 and from 0.82 to 3.68 (mean, 1.81) in 2006. The HR-HPV+ rate for ASC-US
      ranged from 31.5% to 54.6% for individual cytopathologists (mean, 46.1%) in 2005
      and from 29.6% to 61.8% (mean, 45.8%) in 2006. Combined data from both years
      showed only a slight negative correlation for these 2 variables. Both indicators
      together provide useful feedback to cytopathologists. We provide a working schema
      for interpreting perturbations in these indicators to assist in improving the
      quality of gynecologic cytology interpretations.

PMID- 18089495
TI  - Discrepancies between clinical and autopsy diagnoses: a comparison of university,
      community, and private autopsy practices.
AB  - Although it is known that autopsies often disclose unexpected findings, few
      studies have been published that address the effect of institutional setting,
      selection bias, and length of hospitalization. Records of medical autopsies from
      3 institutional settings were studied for discrepancies between clinical and
      autopsy findings. The settings were university hospital (n = 85); community
      hospital (n = 146); and private autopsy (n = 60), which were referred from
      various community hospitals and paid for by family members. The same prosector
      performed the autopsies in the community and private settings. The overall rate
      of major discrepancy that involved the cause of death was 17.2%. Factors that
      increased the likelihood of missed diagnoses were private setting (P = .0005),
      community setting (P = .02), and short hospital stay before death (P = .02).
      Additional major findings were present in 28.5% of autopsies. Length of hospital
      stay before death, institution, and selection bias all affect the rate of major
      unexpected findings in hospital-based autopsies.

PMID- 18089496
TI  - Endometrial endometrioid adenocarcinoma: a pathologic analysis of 827 consecutive
      cases.
AB  - We reviewed 827 consecutive cases of pure endometrial endometrioid adenocarcinoma
      (EEA) treated by hysterectomy to update the distribution of pathologic features.
      Tumor grade (reported in a 2-tiered system), depth of myometrial invasion,
      presence of cervical involvement, lymphovascular invasion (LVI), and evidence of
      extrauterine disease were recorded.The median age at diagnosis was 62 years
      (range, 30-94 years). The tumor was high grade in 94 cases (11.4%), invaded into
      the outer half of the myometrium in 249 (30.1%), was positive for cervical
      involvement in 171 (20.7%), and was positive for LVI in 182 (22.0%). Lymph nodes
      (sampled in 85 cases) were positive in 13 (1.6%), and ovarian metastases were
      present in 15 cases (1.8%). High tumor grade was significantly associated with
      deep myometrial invasion (P > .0001), cervical involvement (P = .0065), and LVI
      (P > .0001).EEA manifests most commonly with low tumor grade and without deep
      myometrial invasion. High tumor grade is significantly associated with deep
      myometrial invasion, cervical involvement, and LVI.

PMID- 18089497
TI  - Review of the cytologic features of noninvasive ductal carcinomas of the
      pancreas: differences from invasive ductal carcinoma.
AB  - Invasive ductal adenocarcinoma (IDA) of the pancreas (IDAP) originating from the
      ductal gland has a poor prognosis. Noninvasive carcinomas are principally
      intraductal papillary mucinous carcinomas (IPMCs) and pancreatic intraepithelial
      neoplasms 3 (PanIN-3). Small papillary-cohesive clusters, individually well
      enveloped nuclei in well-preserved cytoplasm, centrally located nuclei, small
      nuclei (about 10 mum), euchromatin, clearly defined cell borders, small cytoplasm
      without prominent anisocytosis and no cytoplasm more than 21 mum in shortest
      diameter, a mixture of goblet cells, and a pleomorphic aspect are common in IPMC
      and intraductal papillary mucinous neoplasm (IPMN), whereas malignancy in nuclei
      are observed only in IPMC. PanIN-3 cells have small papillary-cohesive and
      compact clusters, a monomorphic aspect, and small dense cytoplasm and are highly
      suggestive of malignancy. IDA cells have loose sheet and solid clusters, poorly
      preserved cytoplasm, nuclei that tend to adhere to each other, large nuclei, a
      combination of large nuclei (short diameter <15 mum) with hyperchromatin, a
      monomorphic aspect, and abundant cytoplasm more than 21 mum in the shortest
      diameter. To preoperatively differentiate noninvasive IPMC and PanIN-3 from IDAP,
      these features would be clinically very useful.

PMID- 18089498
TI  - Leukemia cutis.
AB  - Leukemia cutis (LC) is a nonspecific term used for cutaneous manifestations of
      any type of leukemia. LC has a wide range of cutaneous manifestations, which can
      make it difficult to clinically distinguish LC from other skin lesions. Patients
      with LC usually have concomitant systemic leukemia, but occasionally skin
      involvement precedes the involvement of the bone marrow or peripheral blood.
      Thus, a skin biopsy can be the first indication of the presence of leukemia in a
      subset of patients. The immunophenotyping of routinely processed skin biopsy
      specimens is very useful in establishing the diagnosis of LC. Although the
      molecular mechanisms explaining the pathogenesis of LC are not well defined,
      chemokine receptors and adhesion molecules may have an important role in skin
      tropism. We review the literature and recent advances pertaining to LC, with
      special emphasis on the immunohistochemical assessment and possible mechanisms
      involved in skin tropism by leukemic cells.

PMID- 18089499
TI  - The usefulness of CD26 in flow cytometric analysis of peripheral blood in Sezary
      syndrome.
AB  - The loss of CD26 expression was proposed to be a constant feature of circulating
      Sezary cells by flow cytometric immunophenotyping (FCIP), but the experience with
      CD26 is limited. To establish its usefulness, CD26 results were correlated with
      morphologic, molecular, and immunophenotypic findings. Based on FCIP of 179
      samples of peripheral blood, CD26 negativity was found in 59.3% of cases with
      Sezary syndrome (SS), 33.3% of mycosis fungoides (MF), 14.2% of benign dermatosis
      (BD), and no control cases. In diagnostic subgroups of SS based on morphologic,
      molecular, and immunophenotypic criteria, the percentage of CD26- cases varied
      from 41.1% to 63.6%. The specificity of a CD26- result was inferior to that of T
      cell antigen loss in differentiating SS from MF and BD. CD26 offers lower
      diagnostic performance than previously suggested; however, in addition to the
      findings of major T-cell antigen loss, it could improve sensitivity of FCIP in
      patients with SS.

PMID- 18089500
TI  - Transformation of follicular lymphoma to precursor B-cell lymphoblastic lymphoma
      with c-myc gene rearrangement as a critical event.
AB  - Progression of follicular lymphoma (FL) to a higher-grade lymphoma occurs in 25%
      to 60% of cases and frequently indicates a poor prognosis. The transformation is
      accompanied by alteration in morphologic features and clinical behaviors. Herein,
      we report a case of FL occurring in a 59-year-old woman with the development of a
      precursor B-cell lymphoblastic lymphoma (PBC-LBL) during a 6-month period. Both
      lymphomas had identical bcl-2 and immunoglobulin heavy-chain gene breakpoints as
      assessed by polymerase chain reaction amplification and direct sequencing,
      indicating that the 2 tumors originated from a common precursor B-cell clone or
      the PBC-LBL arose from clonal evolution of its preceding FL and
      "dedifferentiated" into a lymphoblastic stage. Immunohistochemical studies
      revealed that both lymphomas displayed typical phenotypic characteristics. A c
      myc gene translocation was observed in the PBC-LBL but not the FL by fluorescence
      in situ hybridization. The c-myc translocation is also reported in similar cases
      in the literature and likely is crucial in the pathogenesis of the PBC-LBL.

PMID- 18089501
TI  - "Drinking is fun" and "There's nothing you can do about it": the problem with the
      21-year-old minimum drinking age.

PMID- 18089502
TI  - Development and validation of the college drinking influences survey.
AB  - OBJECTIVE: The authors developed and validated measures of college drinking
      expectations, psychosocial influences, and values. PARTICIPANTS: Freshmen at
      college entry (N = 320) and the end of freshman year (N = 420) participated.
      METHODS: The College Drinking Influences Survey, administered in paper and Web
      based versions, consists of 3 distinct scales: (1) the College Drinking
      Expectations Scale assesses expectations for drinking norms and consequences; (2)
      the Psychosocial Drinking Inventory evaluates social influences, stress, and
      sensation seeking; and (3) the Drinking Values Scale assesses drinking decisions
      based on personal choice, social responsibility, and institutional obligation.
      RESULTS: Factor analysis, interitem reliability, and correlations with existing
      instruments demonstrated validity and reliability. Differences between the sexes
      were in predicted directions, and multiple regression using subscale scores as
      predictors accounted for significant variance in drinking behaviors across the
      freshman year. CONCLUSIONS: Data support the usefulness of the scales for
      identifying student alcohol risk and protective factors.

PMID- 18089503
TI  - Support for alcohol-control policies and enforcement strategies among US college
      students at 4-year institutions.
AB  - OBJECTIVE: The authors examined college student support for policies and
      enforcement strategies to reduce alcohol problems on campus. PARTICIPANTS: A
      random sample of students from each of 32 four-year colleges and universities
      participated. METHODS: Students completed an anonymous mail survey. RESULTS: A
      majority of students supported 5 of the 12 policy proposals. Whatever percentage
      of students indicated support for a policy, a far smaller percentage reported
      that other students supported it. The majority at all 32 schools supported using
      stricter disciplinary sanctions for students who engage in alcohol-related
      violence and repeatedly violate campus alcohol policy. The majority at more than
      half of the schools supported applying stricter penalties for the use of false
      IDs to purchase alcohol illegally and prohibiting kegs on campus. CONCLUSIONS:
      Higher-education administrators should survey students to learn which policies a
      majority of their students will endorse.

PMID- 18089504
TI  - Partying before the party: examining prepartying behavior among college students.
AB  - OBJECTIVE: The authors examined the phenomenon known to college students as
      prepartying, which is the consumption of alcohol prior to attending an event or
      activity (eg, party, bar, concert) at which more alcohol may be consumed.
      PARTICIPANTS: To explore the extent of this behavior, the authors surveyed 227
      college students about each drinking event over a 1-month period. RESULTS:
      Principal results revealed that 64% of participants engaged in prepartying (75%
      of drinkers) and that prepartying is involved in approximately 45% of all
      drinking events. Prepartying was predictive of more drinking throughout the day
      of the drinking event and alcohol-related negative consequences. Men and women
      engaged in this behavior at similar rates, and prepartying was most related to
      social reasons for drinking. CONCLUSION: Because prepartying is well-known among
      students, the authors suggest that clinicians and researchers target it to better
      understand college drinking and to help students understand the associated
      dangers.

PMID- 18089505
TI  - Staying safe while consuming alcohol: a qualitative study of the protective
      strategies and informational needs of college freshmen.
AB  - OBJECTIVE: In this qualitative study, the authors examined how students attempt
      to minimize harm to themselves and others when drinking. PARTICIPANTS: The
      authors recruited freshmen at a large, mid-Atlantic US public university during
      the fall semester of 2005 to participate in 8 focus groups. METHODS: The
      moderator's guide was developed through an iterative process that included input
      from experts and pilot testing. The researchers audiotaped focus group
      conversations, transcribed them, and subjected them to an interrater reliability
      check. Analysis was based on the framework of Information-Motivation-Behavioral
      Skills Model and a phenomenological approach. RESULTS: College students have a
      repertoire of coping strategies they use in an attempt to safeguard themselves
      and their friends from harm when drinking. Strategies encompass planning a safe
      context for drinking, using safety measures to minimize harm when drinking, and
      taking care of someone who has consumed too much alcohol. CONCLUSIONS: A harm
      reduction focus that acknowledges and builds on existing protective strategies
      may be a promising avenue for alcohol interventions.

PMID- 18089506
TI  - Alcohol-related fan behavior on college football game day.
AB  - High-risk drinking on game day represents a unique public health challenge.
      OBJECTIVE: The authors examined the drinking behavior of college football fans
      and assessed the support for related interventions. PARTICIPANTS: The authors
      randomly selected 762 football fans, including college students, alumni, and
      other college football fans, to complete an anonymous online game-day survey.
      METHODS: The authors collected data on participants' drinking behaviors and
      support for specific game-day interventions. RESULTS: Analysis revealed that,
      overall, fans drank significantly more on game day than they did the last time
      they partied or socialized. Nondrinkers were the most supportive of game-day
      interventions, followed by moderate drinkers, whereas heavy drinkers offered the
      least support. CONCLUSIONS: With the exception of limiting tailgating hours on
      game day, fans support game-day interventions, including alcohol-free
      alternatives, designating tailgating areas where open containers are permitted,
      and increasing law enforcement efforts.

PMID- 18089507
TI  - Perceived norms and alcohol consumption: differences between college students
      from rural and urban high schools.
AB  - OBJECTIVE: The authors examined perceived norms and drinking among college
      students who attended high schools in rural and urban communities. PARTICIPANTS
      AND METHODS: Undergraduates (99 men and 85 women) who attended high schools in
      communities with populations ranging from less than 100 to more than 400,000
      completed surveys assessing perceived norms and alcohol consumption. RESULTS:
      Analyses revealed that students from smaller towns and in smaller high school
      graduating classes reported heavier drinking and that perceived norms were
      positively associated with drinking. Perceived norms were unrelated to population
      variables, and the relationship between perceived norms and drinking did not vary
      as a function of population variables. Results suggest that differences in
      drinking as a function of coming from more rural areas contribute to drinking
      behavior in college independently of perceived norms. CONCLUSIONS: College
      students may adjust to campus drinking norms relatively quickly, and longitudinal
      research would be useful in understanding this transition.

PMID- 18089508
TI  - High-risk drinking characteristics in collegiate athletes.
AB  - OBJECTIVE: The authors aimed to further describe the relationship of alcohol use
      by college athletes to variables, such as sport participation, time of year, and
      level of competition. PARTICIPANTS: There were 720 participants from Divisions I,
      II, and III who participated in either a team sport or an individual sport.
      METHODS: The authors measured characteristics of alcohol use by college athletes
      at 9 colleges and universities. RESULTS: Participants reported a high rate of
      consuming 5 or more drinks per occasion in the past 2 weeks. There were greater
      percentages of team sport athletes reporting this behavior than athletes of
      individual sports, and there were significant differences according to level of
      competition. CONCLUSIONS: The college athletes in this study reported high-risk
      alcohol use at percentages much higher than previously reported. The findings and
      practical application of the results are discussed.

PMID- 18089509
TI  - Alcohol use and participation in organized recreational sports among university
      undergraduates.
AB  - OBJECTIVE: The authors examined alcohol use among students involved in
      recreational sports. To the authors' knowledge, this is the first study of
      alcohol use in which researchers separate recreational sports participants from
      intercollegiate athletes and examine them as a separate group of interest.
      PARTICIPANTS: The authors generated a random sample of 494 students from the
      undergraduate population at a 4-year university. METHODS: They used a Web-based
      survey to collect data and stratified and weighted the sample by residence status
      to more accurately reflect the population. RESULTS: Students who participated in
      recreational sports used alcohol at a greater frequency and intensity than did
      those who were not involved in recreational sports across a variety of measures,
      even alongside other variables, including race, sex, and Greek membership.
      CONCLUSIONS: On the basis of these findings, alcohol consumption among those
      participating in recreational sports appears to be an area worthy of
      consideration in future research.

PMID- 18089510
TI  - The impact of a tailgating policy on students' drinking behavior and perceptions.
AB  - In the fall of 2004, a midwestern public university changed its tailgating policy
      from one that did not allow alcohol consumption to one that did. OBJECTIVE,
      PARTICIPANTS, AND METHODS: The authors surveyed students before and after the
      policy change to measure consumption, problems, perceptions of peer consumption,
      and reported game attendance. RESULTS: Results showed no change in drinking
      quantities or prevalence of problems after the policy change; however, there was
      an increase in students' misperceptions, with students overestimating drinking
      quantities and the number of students who drank while tailgating. Last, students'
      predictions about their game attendance if alcohol was allowed were higher than
      their reported attendance after the policy change. CONCLUSIONS: Conclusions
      suggest that although drinking quantities may not be influenced by policies at
      tailgating events, misperceptions may be influenced. Administrators should note
      that the policy did not affect students' self-reported game attendance.

PMID- 18089511
TI  - Drinking patterns, problems, and motivations among collegiate bisexual women.
AB  - OBJECTIVE AND PARTICIPANTS: The authors compared the drinking behaviors,
      motivations, and problems of collegiate bisexual women with those of heterosexual
      women (N = 2,788; n = 86 bisexual women). METHODS: Data came from the 2003
      Student Life Survey, a random population-based survey at a large midwestern
      university. The authors explored the hypothesis that bisexual women would be more
      likely than heterosexual women to report drinking motivations related to stress
      and coping as a result of sexual identity stigma. RESULTS: They found that
      bisexual women drank significantly less than did heterosexual women. There were
      few differences between the 2 groups in drinking motivations and problems.
      Bisexual women reported a comparable number of problems related to their drinking
      but were significantly more likely to report contemplating suicide after drinking
      than were heterosexual women. CONCLUSIONS: More research is needed to understand
      the finding that despite lower levels of alcohol consumption, bisexual women
      reported a comparable number of drinking problems. College health educators and
      health care providers need to be aware of findings related to heightened suicidal
      risk among bisexual women.

PMID- 18089512
TI  - Social norms theory-based interventions: testing the feasibility of a purported
      mechanism of action.
AB  - Social norms-based interventions targeting college student drinking behaviors
      have become increasingly popular. Such interventions purportedly modify student
      misperceptions of fellow student drinking behaviors, which leads to changes in
      individual drinking behavior. Despite claims of successful interventions,
      research demonstrating that social norms-based interventions modify student
      perceptions is lacking. OBJECTIVE: The authors conducted a laboratory experiment
      examining the feasibility of this mechanism of action and aimed to determine the
      validity of the campus-specific drinking norms hypothesis. PARTICIPANTS AND
      METHODS: The authors randomly assigned 60 students to 1 of 3 research conditions:
      Alcohol 101 (national drinking norms), a didactic presentation of campus specific
      drinking norms, or a control condition. RESULTS: Both intervention groups
      modified student misperceptions regarding peer alcohol use, and these changes
      were sustained 1 week later. CONCLUSIONS: Social norms-based interventions can
      contribute to more accurate drinking perceptions among college students.

PMID- 18089513
TI  - Understanding the relationship between alcohol and sex: Latino and white college
      students and problematic sexual experiences while drinking.
AB  - OBJECTIVES: The authors examined whether the relationship between alcohol
      expectancies and sexual experiences while drinking differed between Latino and
      white college students. PARTICIPANTS: The authors considered students if they
      were white or Latino, unmarried, aged 18-25 years, reported any drinking, and had
      at least 1 sexual partner in the present school year. METHODS: The investigators
      collected surveys from a random sample of 13,868 undergraduate students from the
      14 California public university campuses. They used tests of group differences
      and hierarchical multiple regressions. RESULTS: Social-facilitation alcohol
      expectancies were associated with the total number of different alcohol-related
      sexual experiences among Latino students. Neither social facilitation nor sexual
      enhancement alcohol expectancies were differentially predictive of white or
      Latino students' frequency of sexual experiences. CONCLUSIONS: Additional
      research is necessary to determine whether concepts targeted by alcohol
      prevention programs operate in a differential manner for Latino students.

PMID- 18089514
TI  - Using theory-based constructs to explore the impact of Greek membership on
      alcohol-related beliefs and behaviors: a systematic literature review.
AB  - By charter, national Greek organizations (ie, fraternities and sororities) place
      an emphasis on upholding personal integrity, academic scholarship, and
      development of campus leaders. Recent concerns, however, assert that the drinking
      behaviors of members of Greek organizations are antithetical to the mission of
      their universities. OBJECTIVE: The author's purpose in this review was to
      systematically examine scientific literature addressing the effect of Greek
      affiliation on alcohol-related beliefs and behaviors. The internal and external
      influences affecting Greek members' alcohol-related beliefs and behaviors are
      organized into a frame-work of various health behavior theories, based on the
      ecological perspective's levels of influence. RESULTS: Results provide a broad
      perspective into the individual characteristics, social peer network, and
      environmental aspects influencing alcohol-related behavior among Greek members.
      Findings suggest that Greek members comprise a subgroup that consumes alcohol in
      greater quantities, underscores and misperceives the risks of alcohol abuse, and
      emulates a social environment and culture in which drinking alcohol is a key part
      of life.

PMID- 18089515
TI  - Unplanned sexual activity as a consequence of alcohol use: a prospective study of
      risk perceptions and alcohol use among college freshmen.
AB  - OBJECTIVE: The authors' goal was to show how risk perceptions regarding unplanned
      sexual activity following alcohol use are prospectively related to subsequent
      alcohol consumption. PARTICIPANTS: Undergraduate students (N = 380) completed
      questionnaires at 2 time points during their freshman year. METHODS: In the
      middle of the academic year (T1), students estimated their risk of engaging in
      unplanned sex and reported their alcohol use during the previous term. Four
      months later (T2), they again reported alcohol use and indicated whether they had
      engaged in unplanned sex since T1. RESULTS: Students who consumed more alcohol at
      T1 rated their risk of unplanned sex more highly, suggesting relative accuracy.
      Those with higher risk perceptions consumed more alcohol at T2 (controlling for
      T1 use), suggesting that they maintained the high-risk behavior. Last, those who
      were unrealistically optimistic (ie, estimated low risk at T1 yet had unplanned
      sex by T2) reported greater alcohol use at T2. CONCLUSIONS: These findings
      highlight the role that risk perceptions regarding sexual activity may play in
      college students' alcohol use.

PMID- 18089516
TI  - Evaluation results of a 21st birthday card program targeting high-risk drinking.
AB  - The B.R.A.D. Birthday Card initiative was started on the campus of Michigan State
      University (MSU) in April 1999. MSU administrators send the safe-drinking 21st
      birthday card (B.R.A.D.) and laminated wallet card to students shortly before
      their 21st birthday. OBJECTIVE: To evaluate the effectiveness of the 21st
      birthday card, MSU and B.R.A.D., Inc, applied for and were awarded a 2-year US
      Department of Education grant in 2001. PARTICIPANTS: The authors surveyed 1,731
      students within 2 weeks of their 21st birthday. METHODS: Of all students turning
      21 years old during the study, the authors randomly selected students for each
      group. A control group received no card. All others received the standard
      B.R.A.D. card or a gender-tailored message card. RESULTS: Key findings include:
      74% of students saved part of the card, 65% shared the card with family or
      friends, 22% reported thinking about the card during their celebration, 12%
      reported drinking less because of the card, 15% reported learning something new
      about alcohol poisoning, and 98% believed that MSU and B.R.A.D. should continue
      sending cards to students. CONCLUSIONS: Receiving, reading, and recalling the
      content of the B.R.A.D. card appears to reduce the total number of drinks a
      celebrant consumes.

PMID- 18089517
TI  - Breeding racehorses: what price good genes?
AB  - Horse racing is a multi-million pound industry, in which genetic information is
      increasingly used to optimize breeding programmes. To maximize the probability of
      producing a successful offspring, the owner of a mare should mate her with a high
      quality stallion. However, stallions with big reputations command higher stud
      fees and paying these is only a sensible strategy if, (i) there is a genetic
      variation for success on the racecourse and (ii) stud fees are an honest signal
      of a stallion's genetic quality. Using data on thoroughbred racehorses, and
      lifetime earnings from prize money (LE) as a measure of success, we performed
      quantitative genetic analyses within an animal model framework to test these two
      conditions. Although LE is heritable (VA=0.299+/-0.108, Pr=0.002), there is no
      genetic variance for stud fee and the genetic correlation between traits is
      therefore zero. This result is supported by an absence of any relationship
      between stud fees for currently active stallions and the predicted LE for their
      (hypothetical) offspring. Thus, while there are good genes to be bought, a
      stallion's fees are not an honest signal of his genetic quality and are a poor
      predictor of a foal's prize winning potential.

PMID- 18089519
TI  - Genetic evidence for co-occurrence of chromosomal and thermal sex-determining
      systems in a lizard.
AB  - An individual's sex depends upon its genes (genotypic sex determination or GSD)
      in birds and mammals, but reptiles are more complex: some species have GSD
      whereas in others, nest temperatures determine offspring sex (temperature
      dependent sex determination). Previous studies suggested that montane scincid
      lizards (Bassiana duperreyi, Scincidae) possess both of these systems
      simultaneously: offspring sex is determined by heteromorphic sex chromosomes (XX
      XY system) in most natural nests, but sex ratio shifts suggest that temperatures
      override chromosomal sex in cool nests to generate phenotypically male offspring
      even from XX eggs. We now provide direct evidence that incubation temperatures
      can sex-reverse genotypically female offspring, using a DNA sex marker.
      Application of exogenous hormone to eggs also can sex-reverse offspring
      (oestradiol application produces XY as well as XX females). In conjunction with
      recent work on a distantly related lizard taxon, our study challenges the notion
      of a fundamental dichotomy between genetic and thermally determined sex
      determination, and hence the validity of current classification schemes for sex
      determining systems in reptiles.

PMID- 18089520
TI  - Comparison of the functional responses of invasive and native amphipods.
AB  - While we can usually understand the impacts of invasive species on recipient
      communities, invasion biology lacks methodologies that are potentially more
      predictive. Such tools should ideally be straightforward and widely applicable.
      Here, we explore an approach that compares the functional responses (FRs) of
      invader and native amphipod crustaceans. Dikerogammarus villosus is a Ponto
      Caspian amphipod currently invading Europe and poised to invade North America.
      Compared with other amphipods that it actively replaces in freshwaters, D.
      villosus exhibited significantly greater predation, consuming significantly more
      prey with a higher type II FR. This corroborates the known dramatic field impacts
      of D. villosus on invaded communities. In another species, FRs were nearly
      identical in invasive and native ranges. We thus propose that if FRs of other
      taxa and trophic groups follow such general patterns, this methodology has
      potential in predicting future invasive species impacts.

PMID- 18089521
TI  - What factors contribute to an ownership advantage?
AB  - In most taxa, owners win fights when defending a territory against intruders. We
      calculated effect sizes for four factors that potentially contribute to an 'owner
      advantage'. We studied male fiddler crabs Uca mjoebergi, where owners won 92% of
      natural fights. Owners were not more successful because they were inherently
      better fighters (r=0.02). There was a small effect (r=0.18) of the owner's
      knowledge of territory quality (food availability) and a medium effect (r=0.29)
      of his having established relations with neighbours (duration of active tenure),
      but neither was statistically significant. There was, however, a significant
      effect due to the mechanical advantage the owner gained through access to the
      burrow during fights (r=0.48, p<0.005).

PMID- 18089522
TI  - Kin recognition in plants?

PMID- 18089523
TI  - Experimental evidence of competitive release in sympatric carnivores.
AB  - Changes in the relative abundance of sympatric carnivores can have far-reaching
      ecological consequences, including the precipitation of trophic cascades and
      species declines. While such observations are compelling, experimental
      evaluations of interactions among carnivores remain scarce and are both
      logistically and ethically challenging. Carnivores are nonetheless a particular
      focus of management practices owing to their roles as predators of livestock and
      as vectors and reservoirs of zoonotic diseases. Here, we provide evidence from a
      replicated and controlled experiment that culling Eurasian badgers Meles meles
      for disease control was associated with increases in red fox Vulpes vulpes
      densities of 1.6-2.3 foxes km-2. This unique experiment demonstrates the
      importance of intraguild relations in determining species abundance and of
      assessing the wider consequences of intervention in predator populations.

PMID- 18089524
TI  - Editorial: Hidden costs and invisible contributions in family caregiving: an
      introduction.

PMID- 18089526
TI  - Invisible contributions in families with children and adults with intellectual
      disabilities.
AB  - For many years there has been an underlying pathology within the literature about
      families with children and adults with intellectual disabilities (Helff &
      Glidden, 1998). This literature has emphasized stress and burden, incapacity and
      dependency, leading to negative stereotyping of families in this context. Over
      the last 2 decades research has led to some important reconceptualizations of how
      families approach their caring, affording an improved understanding of how they
      deploy strengths and resources, and who benefits. This paper reviews this
      thinking, arguing that it provides a suitable context for understanding the scope
      and form of family caregiving contributions that are less visible, and therefore
      less recognized. An attempt is therefore made to chart invisible contributions.
      It is suggested that invisible contributions have implications for thinking about
      human and social capital (Putnam, 2000) as well as for practice in supporting
      families.

PMID- 18089527
TI  - Family caregiving or caregiving alone: who helps the helper?
AB  - This study advances the understanding of family caregiving by examining the
      relationship between adult children caregivers and their helpers. Specifically,
      it focuses on examining "who helps whom" and extends analyses beyond the dyadic
      focus of caregiving in later life. The focus on helping and caregiving addresses
      the variety of contributions and responsibilities involving not only the
      caregiver who was the target respondent in this research, but also others
      identified as helpers in the provision of care. The data for this study are
      derived from the Work and Eldercare Research group of CARNET: The Canadian Aging
      Research Network. Secondary analysis of CARNET data focuses on data collected
      from 250 individuals with significant caregiving responsibilities for at least
      one older person. Findings extend Kahn & Antonucci's convoys of social support
      model (1981) and Cantor's model of social care (1991) by disentangling some of
      the dimensions of helping and caregiving, such as the distinction between direct
      and assistive help.

PMID- 18089528
TI  - Equity matters: doing fairness in the context of family caregiving.
AB  - Although family scholars conceptualize caregiving in terms of networks of carers,
      little attention has been given to equity within these groups. Siblings comprise
      a prevalent caregiving network of members who feel responsible for parent care,
      expect to share these responsibilities with each other, and look to each other to
      evaluate the fairness of their sharing. In this paper, a multidisciplinary
      approach is used to examine sibling views of equity in relation to disputes over
      giving parent care and receiving parent assets. A literary perspective is offered
      through analysis of stepsibling tensions depicted in the novel Family Matters.
      Real life disputes among biological siblings that have been pursued through the
      courts are also examined. Issues arising from these examples are then analysed
      through the lens of legal doctrines of equity. Siblings evaluating fairness
      undertake careful comparisons of their respective relationships with parents in
      terms of biological links to parents and type and extent of influence in
      interactions with parents.

PMID- 18089529
TI  - Social network data validity: the example of the social network of caregivers of
      older persons with Alzheimer-type dementia.
AB  - This article offers reflection on the validity of relational data such as used in
      social network analysis. Ongoing research on the transformation of the support
      network of caregivers of persons with an Alzheimer-type disease provides the data
      to fuel the debate on the validity of participant report. More specifically, we
      sought to understand the factors that might influence the description of the
      support network by persons involved in caregiving. The issue warrants special
      attention, given that social relations - in their form and their content -
      constitute the raw material of network analysis. We propose that how persons
      describe their social network corresponds to a subjective process that rests, in
      part, on their representation of their cultural and social universe.

PMID- 18089530
TI  - "They suffered with us and should be compensated": entitling caregivers of
      Canada's veterans.
AB  - This article examines the struggle to win lifetime eligibility for selected home
      care benefits provided through the Veterans Independence Program (VIP) for
      veterans' widows in recognition of their years of unpaid caregiving - a policy
      change eventually implemented between 2003 and 2004. It explores how arguments on
      their behalf shifted from discourses of dependency, cost-saving, and compassion
      to ones of entitlement and commemoration between 1981 and 2004 as the large
      cohort of Second World War veterans and their wives moved towards the end of
      their lives. This policy victory for veterans' widows marked a historic shift in
      mandate for Veterans Affairs Canada and an important recognition by the state of
      unpaid caregiving as a form of national service. If Canadians are to learn from
      this example, however, it must be through seeing all caregiving labour - not just
      that of veterans' wives - as equally heroic and worthy of compensation.

PMID- 18089531
TI  - Cultural predictors of caregiving burden of Chinese-Canadian family caregivers.
AB  - The growth of research knowledge on culturally diverse family caregivers for the
      aging population lags behind the increase of culturally diverse populations in
      Canada. This study examines the effects of culture, as manifested through
      cultural variables, on the caregiving burden of family caregivers in a Chinese
      Canadian community. A random sample of 339 Chinese-Canadian caregivers for
      elderly relatives completed a telephone survey. Results of hierarchical stepwise
      multiple regression analysis reported the predicting effects of culture-related
      variables on caregiving burden. The findings indicated that being an immigrant,
      having a Western or non-Western religion as compared to having no religion, and
      having a lower level of filial piety, predicted a higher level of caregiving
      burden. Chinese tradition does not exempt the caregivers from being burdened.
      Policies and practices should address the needs of family caregivers according to
      the intra-cultural variations identified in this study.

PMID- 18089532
TI  - A comparative analysis of costs to government for home care and long-term
      residential care services, standardized for client care needs.
AB  - This paper reports on the results of analyses using administrative data from
      British Columbia for 10 years from fiscal 1987/1988 to 1996/1997, inclusive, to
      examine the comparative costs to government of long-term home care and
      residential care services. The analyses used administrative data for hospital
      care, physician care, drugs, and home care and residential long-term care. Direct
      comparisons for cost and utilization data were possible, as the same care-level
      classification system is used in BC for home care and residential care clients.
      Given significant changes in the type and/or level of care of clients over time,
      a full-time equivalent client strategy was used to maximize the accuracy of
      comparisons. The findings suggest that, in general, home care can be a lower-cost
      alternative to residential care for clients with similar care needs. The
      difference in costs between home care and residential care services narrows
      considerably for those who change their type and/or level of care, and home care
      was found to be more costly than long-term institutional care for home care
      clients who died. The findings from this study indicate that with the appropriate
      substitution for residential care services, in a planned and targeted manner,
      home care services can be a lower-cost alternative to residential long-term care
      in integrated systems of care delivery that include both sets of services.

PMID- 18089533
TI  - Sexual selection mediated by the thermoregulatory effects of male colour pattern
      in the ambush bug Phymata americana.
AB  - Sexual dimorphism in coloration is a taxonomically widespread phenomenon often
      attributed to sexual selection on visual signals. However, the ambush bug Phymata
      americana exhibits sexual dimorphism in coloration that has no apparent
      signalling function. Here we provide evidence that colour pattern in this species
      influences male mating success indirectly through its effect on thermoregulation.
      We demonstrate, using experimental manipulation, that individuals with dark
      colour pattern achieve higher thoracic temperatures under illumination. We also
      show that dark colour pattern predicted mate-searching success but only under
      thermally challenging conditions (i.e. cool ambient temperature). As far as we
      are aware, this is the first study to provide evidence that sexual dimorphism can
      be accounted for by sexual selection on thermoregulatory performance.

PMID- 18089534
TI  - More 'altruistic' punishment in larger societies.
AB  - If individuals will cooperate with cooperators, and punish non-cooperators even
      at a cost to themselves, then this strong reciprocity could minimize the cheating
      that undermines cooperation. Based upon numerous economic experiments, some have
      proposed that human cooperation is explained by strong reciprocity and norm
      enforcement. Second-party punishment is when you punish someone who defected on
      you; third-party punishment is when you punish someone who defected on someone
      else. Third-party punishment is an effective way to enforce the norms of strong
      reciprocity and promote cooperation. Here we present new results that expand on a
      previous report from a large cross-cultural project. This project has already
      shown that there is considerable cross-cultural variation in punishment and
      cooperation. Here we test the hypothesis that population size (and complexity)
      predicts the level of third-party punishment. Our results show that people in
      larger, more complex societies engage in significantly more third-party
      punishment than people in small-scale societies.

PMID- 18089535
TI  - Diel variation in a dynamic sexual display and its association with female mate
      searching behaviour.
AB  - Dynamic sexual signals often show a diel rhythm and may vary substantially with
      time of day. Diel and short-term fluctuations in such sexual signals pose a
      puzzle for condition capture models of mate choice, which assume a female
      preference for male traits that reliably reflect a male's quality. Here we
      experimentally manipulated the food supply of individual male field crickets
      Gryllus campestris in their natural habitat in two consecutive seasons to
      determine (i) the effect of male nutritional condition on the fine-scaled
      variation of diel investment in acoustic signalling and (ii) the temporal
      association between the diel variation in male signalling and female mate
      searching behaviour. Overall food-supplemented males signalled more often, but
      the effect was only visible during the daytime. In the evening and the night,
      signal output was still high but the time spent signalling was unrelated to a
      male's nutritional condition. Females' mate-searching behaviour also showed a
      diel rhythm with peak activity during the afternoon, when differences among
      calling males were highest, and where signal output reliably reflects male
      quality. These findings suggest that males differing in nutritional condition may
      optimize their investment in signalling in relation to time of day as to maximize
      mating success.

PMID- 18089536
TI  - Female Barbary macaque (Macaca sylvanus) copulation calls do not reveal the
      fertile phase but influence mating outcome.
AB  - In a number of primate species, females utter loud and distinctive calls during
      mating. Here we aim to clarify the information content and function of Barbary
      macaque (Macaca sylvanus) copulation calls by testing (i) whether or not
      copulation calls advertise the female fertile phase and (ii) whether and how
      copulation calls influence male ejaculatory behaviour. In order to do this, we
      combined hormone measurements with acoustic analysis and behavioural
      observations. In contrast to a previous study implying that the structure of
      copulation calls indicates the timing of the fertile phase, our results, using
      objective endocrine criteria for assessing ovulation, provide evidence that the
      structure of copulation calls of female Barbary macaques does not reveal the
      timing of the fertile phase. More importantly, females seem to influence the
      likelihood of ejaculation by calling versus remaining silent and by adjusting the
      timing of call onset. Females make use of this ability to influence mating
      outcome to ensure ejaculatory matings with almost all males in the group. In
      addition, calls given during ejaculatory copulations differ from those during non
      ejaculatory copulations, providing information about mating outcome for
      listeners. We conclude that in this species, copulation calls apparently serve to
      enhance sperm competition and maximize paternity confusion.

PMID- 18089537
TI  - Running, swimming and diving modifies neuroprotecting globins in the mammalian
      brain.
AB  - The vulnerability of the human brain to injury following just a few minutes of
      oxygen deprivation with submergence contrasts markedly with diving mammals, such
      as Weddell seals (Leptonychotes weddellii), which can remain underwater for more
      than 90 min while exhibiting no neurological or behavioural impairment. This
      response occurs despite exposure to blood oxygen levels concomitant with human
      unconsciousness. To determine whether such aquatic lifestyles result in unique
      adaptations for avoiding ischaemic-hypoxic neural damage, we measured the
      presence of circulating (haemoglobin) and resident (neuroglobin and cytoglobin)
      oxygen-carrying globins in the cerebral cortex of 16 mammalian species considered
      terrestrial, swimming or diving specialists. Here we report a striking difference
      in globin levels depending on activity lifestyle. A nearly 9.5-fold range in
      haemoglobin concentration (0.17-1.62 g Hb 100 g brain wet wt(-1)) occurred
      between terrestrial and deep-diving mammals; a threefold range in resident
      globins was evident between terrestrial and swimming specialists. Together, these
      two globin groups provide complementary mechanisms for facilitating oxygen
      transfer into neural tissues and the potential for protection against reactive
      oxygen and nitrogen groups. This enables marine mammals to maintain sensory and
      locomotor neural functions during prolonged submergence, and suggests new avenues
      for averting oxygen-mediated neural injury in the mammalian brain.

PMID- 18089538
TI  - Impact of plant nutrients on the relationship between a herbivorous insect and
      its symbiotic bacteria.
AB  - The interactions between herbivorous insects and their symbiotic micro-organisms
      can be influenced by the plant species on which the insects are reared, but the
      underlying mechanisms are not understood. Here, we identify plant nutrients,
      specifically amino acids, as a candidate factor affecting the impact of symbiotic
      bacteria on the performance of the phloem-feeding aphid Aphis fabae. Aphis fabae
      grew more slowly on the labiate plant Lamium purpureum than on an alternative
      host plant Vicia faba, and the negative effect of L. purpureum on aphid growth
      was consistently exacerbated by the bacterial secondary symbionts Regiella
      insecticola and Hamiltonella defensa, which attained high densities in L.
      purpureum-reared aphids. The amino acid content of the phloem sap of L. purpureum
      was very low; and A. fabae on chemically defined diets of low amino acid content
      also grew slowly and had elevated secondary symbiont densities. It is suggested
      that the phloem nutrient profile of L. purpureum promotes deleterious traits in
      the secondary symbionts and disturbs insect controls over bacterial abundance.

PMID- 18089539
TI  - Compatibility counts: MHC-associated mate choice in a wild promiscuous primate.
AB  - The mechanisms and temporal aspects of mate choice according to genetic
      constitution are still puzzling. Recent studies indicate that fitness is
      positively related to diversity in immune genes (MHC). Both sexes should
      therefore choose mates of high genetic quality and/or compatibility. However,
      studies addressing the role of MHC diversity in pre- and post-copulatory mate
      choice decisions in wild-living animals are few. We investigated the impact of
      MHC constitution and of neutral microsatellite variability on pre- and post
      copulatory mate choice in both sexes in a wild population of a promiscuous
      primate, the grey mouse lemur (Microcebus murinus). There was no support for pre
      copulatory male or female mate choice, but our data indicate post-copulatory mate
      choice that is associated with genetic constitution. Fathers had a higher number
      of MHC supertypes different from those of the mother than randomly assigned
      males. Fathers also had a higher amino acid distance to the females' MHC as well
      as a higher total number of MHC supertypes and a higher degree of microsatellite
      heterozygosity than randomly assigned males. Female cryptic choice may be the
      underlying mechanism that operates towards an optimization of the genetic
      constitution of offspring. This is the first study that provides support for the
      importance of the MHC constitution in post-copulatory mate choice in non-human
      primates.

PMID- 18089540
TI  - Adaptive developmental plasticity in growing nestlings: sibling competition
      induces differential gape growth.
AB  - Sibling competition has been shown to affect overall growth rates in birds.
      However, growth consists on the coordinated development of a multitude of
      structures, and there is ample scope for developmental plasticity and trade-offs
      among these structures. We would expect that the growth of structures that are
      used in sibling competition, such as the gape of altricial nestlings, should be
      prioritized under intense competition. We conducted an experiment in the spotless
      starling (Sturnus unicolor), cross-fostering nestlings to nests with different
      levels of sibling competition. We predicted that nestlings subjected to higher
      levels of sibling competition should develop larger gapes than control birds. We
      found that, halfway through the nestling period, overall size (a composite index
      of mass, wing, tarsus and bill) was reduced in nests with intense sibling
      competition, whereas gape width remained unaffected. At the end of the nestling
      period, experimental nestlings had wider gapes than controls. Additionally, a
      correlative study showed that nestling gape width increased when feeding
      conditions worsened and overall size decreased. These patterns could either be
      due to increased growth of gape flanges or to delayed reabsorption of this
      structure. Our results show that birds can invest differentially in the
      development of organs during growth, and that the growth of organs used in
      sibling competition is prioritized over structural growth.

PMID- 18089541
TI  - Could BNP screening of acute chest pain cases lead to safe earlier discharge of
      patients with non-cardiac causes? A pilot study.
AB  - BACKGROUND: The assessment of chest pain relies on clinical assessment and
      markers of cell necrosis such as Troponin T (TnT). B-type natriuretic peptide
      (BNP) is also raised in myocardial ischaemia and therefore may be useful in
      deciding if acute chest pain is of cardiac origin or not. AIM: To investigate the
      role of BNP in the assessment of unselected patients presenting with acute chest
      pain. METHODS: A prospective observational study of 100 patients presenting with
      chest pain to the Acute Medical Admissions Unit was carried out. All patients had
      BNP and TnT levels measured. The primary outcome was categorization of chest pain
      as cardiac or non-cardiac. This was determined by the discharge diagnosis. BNP
      cutoffs were derived from a receiver operated characteristic (ROC) curve. The
      sensitivity, specificity, positive predictive accuracy (PPA) and negative
      predictive accuracy (NPA) were all calculated for BNP, TnT and for the composite
      of BNP and TnT. RESULTS: Mean BNP in patients with cardiac chest pain was
      significantly greater than mean BNP for patients with non-cardiac chest pain (P
      </= 0.0001). BNP was significantly more sensitive than TnT (P = 0.003). However
      TnT was more specific than BNP (98% vs. 75%, P </= 0.0001). Combining BNP and TnT
      increased sensitivity from 55.6% to 95.6%. CONCLUSION: Our findings suggest that
      BNP is more sensitive but less specific than TnT in the diagnostic assessment of
      acute chest pain. However, combining BNP and TnT was a very satisfactory rule out
      test (negative predictive accuracy 96%) for excluding chest pain that had a
      cardiac origin.

PMID- 18089542
TI  - The value of clinical features in the diagnosis of acute pulmonary embolism:
      systematic review and meta-analysis.
AB  - BACKGROUND: Clinical assessment of patients with suspected pulmonary embolus (PE)
      is used to estimate the probability of PE and determine what (if any) diagnostic
      testing is required. AIM: We aimed to estimate the diagnostic value of individual
      clinical features used to determine the pre-test probability of acute PE. DESIGN:
      Systematic review and meta-analysis. METHODS: We searched electronic databases
      (1966 to May 2007) and the bibliographies of retrieved articles for any article
      that reported the diagnostic performance of clinical features compared to a
      reference standard diagnostic test in patients with suspected acute pulmonary
      embolism. Likelihood ratios were calculated for each feature and pooled using a
      random effects model, as implemented by MetaDiSc statistical software. RESULTS:
      We identified 18 studies for inclusion with a total of 5997 patients. The most
      useful features (pooled likelihood ratio) for ruling in PE were syncope (2.38),
      shock (4.07), thrombophlebitis (2.20), current DVT (2.05), leg swelling (2.11),
      sudden dyspnoea (1.83), active cancer (1.74), recent surgery (1.63), haemoptysis
      (1.62) and leg pain (1.60); while the most useful features for ruling out PE were
      the absence of sudden dyspnoea (0.430), any dyspnoea (0.521) and tachypnea
      (0.561). All other clinical features had likelihood ratios near to one. Many of
      the analyses involved pooling results that had significant heterogeneity, so
      these estimates should be used with caution. CONCLUSION: Individual clinical
      features only slightly raise or lower the probability of PE. In isolation, they
      have limited diagnostic value and none can be used to rule in or rule out PE
      without further testing.

PMID- 18089543
TI  - Holter monitoring for syncope: diagnostic yield in different patient groups and
      impact on device implantation.
AB  - BACKGROUND: Holter monitoring is routinely used in patients referred for the
      evaluation of syncope, but its diagnostic value in different patient groups is
      unclear, as is its impact on device implantation (pacemaker or cardioverter
      defibrillator). AIM: To determine the diagnostic yield of Holter monitoring in
      the routine evaluation of syncope, and its impact on subsequent device
      implantation. DESIGN: Retrospective record review. METHODS: We reviewed all
      Holter studies in patients referred with syncope between 2000 and 2005. Strict
      criteria were applied to determine whether a study was diagnostic. The diagnostic
      value of Holter monitoring (overall and in five subgroups: age, gender,
      structural heart disease, ejection fraction, medication) and its impact on the
      implantation of devices, were determined. RESULTS: Of 4877 Holter studies, 826
      were performed in patients with syncope (age 72 +/- 15 years): 71 (8.6%) were
      considered to explain the syncope. Structural heart disease, ejection fraction
      and age were significant predictors of a diagnostic study (all p < 0.01), whereas
      gender and cardiac medication were not. A device was implanted in 33 patients
      (4.4%) whose initial Holter did not explain their syncope, after mean 7 months,
      whereas 45 patients (5.4%) received a pacemaker based on the Holter results (p =
      0.32). DISCUSSION: The overall diagnostic yield of Holter monitoring in the
      evaluation of syncope was 8.6%, with dramatic differences between subgroups. Our
      data suggest that the impact of Holter monitoring on device implantation is
      generally overestimated.

PMID- 18089544
TI  - Diagnosing temporal arteritis: duplex vs. biopsy.
AB  - BACKGROUND: Temporal artery biopsy is the traditionally-accepted method of
      diagnosing temporal arteritis, but is of limited sensitivity. AIM: To compare the
      clinical decisions made after negative temporal artery biopsy vs. negative
      temporal artery duplex, and the effects on patient outcomes. DESIGN:
      Retrospective analysis. METHODS: Of 290 patients suspected of having temporal
      arteritis, 147 underwent bilateral temporal artery duplex with a negative result,
      and 143 underwent unilateral temporal artery biopsy with a negative result. These
      groups were compared. Dependent measures included the proportion of patients in
      each group whose steroids were discontinued by their primary care doctor after
      either negative test, and the difference in the number of alternative diagnoses
      considered after a negative test. The incidence of blindness in each group was
      also compared, as a measure of adverse outcomes. Patients were then stratified by
      pre-test probability of having the disease, and compared using the same measures.
      RESULTS: Equivalent proportions of patients in the two groups had steroids
      discontinued after a negative test result, even when further stratified into risk
      groups by the probability of having temporal arteritis. No differences in adverse
      outcomes or number of alternative diagnoses considered were noted between groups.
      DISCUSSION: In clinical practice, bilateral temporal artery duplex served the
      same function as biopsy, but without subjecting patients to the potential
      morbidity of a surgical procedure. Temporal artery biopsy could be reserved only
      for situations where the duplex result is inconsistent with the clinical picture,
      and the biopsy result, if different from the duplex result, might influence the
      treatment decision.

PMID- 18089545
TI  - A communication model for encouraging optimal care at the end of life for
      hospitalized patients.
AB  - Multiple studies have demonstrated that treatment at or near the end of life is
      rarely optimal. Unwanted death-prolonging treatments are frequently provided and
      open communication about death and dying is often lacking. Early effective
      communication about goals, prognosis and options would improve patient care at or
      near the end of life by enhancing choice and facilitating palliative care. A five
      step sequential approach to communicating with patients at risk of dying in
      hospital about treatment goals and outcomes (and/or their family members) is
      presented. The five steps are founded upon the recognition that trials of life
      sustaining treatments are also, by definition, trials of palliative care. A
      narrative review of currently available qualitative and quantitative research is
      used to support the recommendations.

PMID- 18089546
TI  - Judging words rather than journals or authors: a reminder that peer review
      continues after publication.

PMID- 18089547
TI  - From the depths.

PMID- 18089548
TI  - The H-Invitational Database (H-InvDB), a comprehensive annotation resource for
      human genes and transcripts.
AB  - Here we report the new features and improvements in our latest release of the H
      Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive
      annotation resource for human genes and transcripts. H-InvDB, originally
      developed as an integrated database of the human transcriptome based on extensive
      annotation of large sets of full-length cDNA (FLcDNA) clones, now provides
      annotation for 120 558 human mRNAs extracted from the International Nucleotide
      Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest
      release H-InvDB_4.6. We mapped those human transcripts onto the human genome
      sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which
      could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding
      loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all
      these transcripts and genes, we provide comprehensive annotation including gene
      structures, gene functions, alternative splicing variants, functional non-protein
      coding RNAs, functional domains, predicted sub cellular localizations, metabolic
      pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite
      repeat motifs, co-localization with orphan diseases, gene expression profiles,
      orthologous genes, protein-protein interactions (PPI) and annotation for gene
      families. The current H-InvDB annotation resources consist of two main views:
      Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H
      ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and
      the Gene family/group.

PMID- 18089549
TI  - The Rice Annotation Project Database (RAP-DB): 2008 update.
AB  - The Rice Annotation Project Database (RAP-DB) was created to provide the genome
      sequence assembly of the International Rice Genome Sequencing Project (IRGSP),
      manually curated annotation of the sequence, and other genomics information that
      could be useful for comprehensive understanding of the rice biology. Since the
      last publication of the RAP-DB, the IRGSP genome has been revised and
      reassembled. In addition, a large number of rice-expressed sequence tags have
      been released, and functional genomics resources have been produced worldwide.
      Thus, we have thoroughly updated our genome annotation by manual curation of all
      the functional descriptions of rice genes. The latest version of the RAP-DB
      contains a variety of annotation data as follows: clone positions, structures and
      functions of 31 439 genes validated by cDNAs, RNA genes detected by massively
      parallel signature sequencing (MPSS) technology and sequence similarity, flanking
      sequences of mutant lines, transposable elements, etc. Other annotation data such
      as Gnomon can be displayed along with those of RAP for comparison. We have also
      developed a new keyword search system to allow the user to access useful
      information. The RAP-DB is available at: http://rapdb.dna.affrc.go.jp/ and
      http://rapdb.lab.nig.ac.jp/.

PMID- 18089550
TI  - Quantitative analysis of snake venoms using soluble polymer-based isotope
      labeling.
AB  - We present the design and synthesis of a new quantitative strategy termed soluble
      polymer-based isotope labeling (SoPIL) and its application as a novel and
      inclusive method for the identification and relative quantification of individual
      proteins in complex snake venoms. The SoPIL reagent selectively captures and
      isolates cysteine-containing peptides, and the subsequent tagged peptides are
      released and analyzed using nanoflow liquid chromatography-tandem mass
      spectrometry. The SoPIL strategy was used to quantify venom proteins from two
      pairs of venomous snakes: Crotalus scutulatus scutulatus type A, C. scutulatus
      scutulatus type B, Crotalus oreganus helleri, and Bothrops colombiensis. The
      hemorrhagic, hemolytic, clotting ability, and fibrinogenolytic activities of
      crude venoms were measured and correlated with difference in protein abundance
      determined by the SoPIL analysis. The SoPIL approach could provide an efficient
      and widely applicable tool for quantitative proteomics.

PMID- 18089551
TI  - Comparative evaluation of current peptide production platforms used in absolute
      quantification in proteomics.
AB  - Absolute quantification of peptides by mass spectrometry requires a reference,
      frequently using heavy isotope-coded peptides as internal standards. These
      peptides have traditionally been generated by chemical stepwise synthesis.
      Recently a new way to supply such peptides was described in which nucleotide
      sequences coding for the respective peptides are concatenated into a synthetic
      gene (QconCAT). These QconCATs are then expressed to produce a polypeptide
      consisting of concatenated peptides, purified, quantified by various methods, and
      then digested to yield the final internal standard peptides. Although both of
      these methods for peptide production are routinely used for absolute
      quantifications, there is currently no information regarding the accuracy of the
      quantifications made in each case. In this study, we used sets of synthetic and
      biological peptides in parallel to evaluate the accuracy of either method. We
      also addressed some technical issues regarding the preparation and proper
      utilization of such standard peptides. Twenty-five peptides derived from the
      Caenorhabditis elegans proteome were selected for this study. Twenty-four were
      successfully chemically synthesized. Five QconCAT genes were designed, each a
      concatenation of the same 25 peptides but each in separate, different randomized
      order, and expressed via in vitro translation reactions that contained heavy
      isotope-labeled lysine and arginine. Three of the five QconCATs were successfully
      produced. Different digestion conditions, including various detergents and
      incubation conditions, were tested to find those optimal for the generation of a
      reproducible and accurate reference sample mixture. All three QconCAT
      polypeptides were then digested using the optimized conditions and then mixed in
      a 1:1 ratio with their synthetic counterparts. Multireaction monitoring mass
      spectrometry was then used for quantification. Results showed that the digestion
      protocol had a significant impact on equimolarity of final peptides, confirming
      the need for optimization. Under optimal conditions, however, most QconCAT
      peptides were produced at an equimolar ratio. A few QconCAT-derived peptides were
      largely overestimated due to problems with solubilization or stability of the
      synthetic peptides. Although the order in which the peptide sequences appeared in
      the QconCAT sequence proved to affect the success rate of in vitro translation,
      it did not significantly affect the final peptide yields. Overall neither the
      chemical synthesis nor the recombinant genetic approach proved to be superior as
      a method for the production of reference peptides for absolute quantification.

PMID- 18089552
TI  - Online psychoeducational support for infertile women: a randomized controlled
      trial.
AB  - BACKGROUND: The study goal was to develop and test the effectiveness of a brief
      online education and support program for female infertility patients. METHODS: A
      randomized-controlled trial was conducted. Using a Solomon-four group design, 190
      female patients were recruited from three US fertility centers and were
      randomized into two experimental and two no-treatment control groups. The
      psychological outcomes assessed included infertility distress, infertility self
      efficacy, decisional conflict, marital cohesion and coping style. Program dosage
      and satisfaction were also assessed at four weeks follow-up. RESULTS: Women
      exposed to the online program significantly improved in the area of social
      concerns (P = 0.038) related to infertility distress, and felt more informed
      about a medical decision with which they were contending (P = 0.037). Trends were
      observed for decreased global stress(P = 0.10), sexual concerns (P = 0.059),
      distress related to child-free living (P = 0.063), increased infertility self
      efficacy (P = 0.067) and decision making clarity (P = 0.079). A dosage response
      was observed in the experimental groups for women who spent >60 min online for
      decreased global stress (P = 0.028) and increased self efficacy (P = 0.024).
      CONCLUSIONS: This evidence-based eHealth program for women experiencing
      infertility suggests that a web-based patient education intervention can have
      beneficial effects in several psychological domains and may be a cost effective
      resource for fertility practices.

PMID- 18089553
TI  - Helping themselves to get pregnant: a qualitative longitudinal study on the
      information-seeking behaviour of infertile couples.
AB  - BACKGROUND: Couples seeking infertility treatment are generally hungry for
      information about available therapeutic options and how to help themselves
      achieve pregnancy. This study examined couples' perceptions of the information
      available from various sources in the context of achieved pregnancy or continuing
      treatment. METHODS: A 3 year prospective interview study started in April 2004,
      following couples undergoing infertility treatment at a tertiary fertility clinic
      at Aberdeen Maternity Hospital. Fifty-four couples were invited to participate.
      Up to three semi-structured interviews took place, and were analysed thematically
      using a variation of grounded theory. RESULTS: Twenty-seven couples agreed to
      participate and of the 25 couples followed up, 11 were diagnosed with unexplained
      infertility. The age range of the women was 22-41 years. All hoped to be given
      information on helping themselves to achieve pregnancy, spontaneous or assisted,
      and 19 of the 25 couples became pregnant. Most couples were dissatisfied with the
      written and verbal information routinely provided by the fertility clinic because
      it suggested lifestyle changes they had already attempted to adopt. They sought
      additional information from the internet, books and magazines. Those who became
      pregnant were generally empowered by the experience and thought that it had
      helped them to conceive. Women who were still undergoing treatment however,
      sometimes became distressed, blaming themselves for failing to follow the
      lifestyle advice provided. CONCLUSIONS: Couples, especially those diagnosed with
      unexplained infertility, seek information to help themselves conceive, but only
      those who succeed find it an empowering experience.

PMID- 18089554
TI  - The role of sperm proteasomes during sperm aster formation and early zygote
      development: implications for fertilization failure in humans.
AB  - BACKGROUND Sperm aster organization during bovine and human fertilization
      requires a paternally-derived centriole that must first disengage from the sperm
      tail connecting-piece. We investigated the participation of the 26S proteasome in
      this process. METHODS Proteasome localization and enzymatic activity were studied
      in normal and pathological human spermatozoa by immunocytochemistry and enzyme
      substrate assays. The role of proteasomes during bovine zygote development was
      investigated using a pharmacological proteasome-inhibitor, MG132, and with anti
      proteasome antibodies delivered by Streptolysin O-permeabilization or with the
      Chariot reagent. Human zygotes discarded after ICSI failures (n = 28) were also
      examined. RESULTS Proteasomes were localized in the sperm acrosome and connecting
      piece, as well as in the pronuclei of bovine and human zygotes. Proteasomal
      enzymatic activities were decreased in defective human spermatozoa. Disrupted
      sperm aster formation and pronuclear development were found after pharmacological
      and immunological block of proteasomes in human/bovine spermatozoa and oocytes,
      as well as in 28 discarded human post-ICSI fertilization failures. CONCLUSIONS
      Specific proteasome inhibition disrupts sperm aster formation and pronuclear
      development/apposition in bovine and human zygotes. Human spermatozoa with
      defective centriolar/pericentriolar structures have decreased proteasomal
      enzymatic activity. Release of a functional sperm centriole that acts as a zygote
      microtubule-organizing center probably relies on selective proteasomal
      proteolysis. These findings suggest an important role of sperm proteasomes in
      zygotic development.

PMID- 18089555
TI  - Polyamine acetylation modulates polyamine metabolic flux, a prelude to broader
      metabolic consequences.
AB  - Recent studies suggest that overexpression of the polyamine-acetylating enzyme
      spermidine/spermine N(1)-acetyltransferase (SSAT) significantly increases
      metabolic flux through the polyamine pathway. The concept derives from the
      observation that SSAT-induced acetylation of polyamines gives rise to a
      compensatory increase in biosynthesis and presumably to increased flow through
      the pathway. Despite the strength of this deduction, the existence of heightened
      polyamine flux has not yet been experimentally demonstrated. Here, we use the
      artificial polyamine precursor 4-fluoro-ornithine to measure polyamine flux by
      tracking fluorine unit permeation of polyamine pools in human prostate carcinoma
      LNCaP cells. Conditional overexpression of SSAT was accompanied by a massive
      increase in intracellular and extracellular acetylated spermidine and by a 6-20
      fold increase in biosynthetic enzyme activities. In the presence of 300 microM 4
      fluoro-ornithine, SSAT overexpression led to the sequential appearance of
      fluorinated putrescine, spermidine, acetylated spermidine, and spermine. As
      fluorinated polyamines increased, endogenous polyamines decreased, so that the
      total polyamine pool size remained relatively constant. At 24 h, 56% of the
      spermine pool in the induced SSAT cells was fluorine-labeled compared with only
      12% in uninduced cells. Thus, SSAT induction increased metabolic flux by
      approximately 5-fold. Flux could be interrupted by inhibition of polyamine
      biosynthesis but not by inhibition of polyamine oxidation. Overall, the findings
      are consistent with a paradigm whereby flux is initiated by SSAT acetylation of
      spermine and particularly spermidine followed by a marked increase in key
      biosynthetic enzymes. The latter sustains the flux cycle by providing a constant
      supply of polyamines for subsequent acetylation by SSAT. The broader metabolic
      implications of this futile metabolic cycling are discussed in detail.

PMID- 18089556
TI  - TINY, a dehydration-responsive element (DRE)-binding protein-like transcription
      factor connecting the DRE- and ethylene-responsive element-mediated signaling
      pathways in Arabidopsis.
AB  - Dehydration-responsive element-binding proteins (DREBs) and ethylene-responsive
      element (ERE) binding factors are two major subfamilies of the AP2/ethylene
      responsive element-binding protein family and play crucial roles in the
      regulation of abiotic- and biotic-stress responses, respectively. In the present
      work, we have reported a previously identified DREB-like factor, TINY, that was
      involved in both abiotic- and biotic-stress signaling pathways. TINY was capable
      of binding to both DRE and ERE with similar affinity and could activate the
      expression of reporter genes driven by either of these two elements in tobacco
      cells. The 15th amino acid in the APETALA2 (AP2)/ethylene-responsive element
      binding factor domain was demonstrated to be essential for its specific binding
      to ERE, whereas the 14th and 19th amino acids were responsible for the binding to
      DRE. The expression of TINY was greatly activated by drought, cold, ethylene, and
      slightly by methyl jasmonate. Additionally, overexpression of TINY in Arabidopsis
      resulted in elevated expressions of both the DRE- and the ERE-containing genes.
      Moreover, the expression of DRE-regulated genes, such as COR6.6 and ERD10, was up
      regulated upon ethylene treatment, and the expression of ERE-regulated genes,
      such as HLS1, was also increased by cold stress, when the expression of TINY was
      being induced. These results strongly suggested that TINY might play a role in
      the cross-talk between abiotic- and biotic-stress-responsive gene expressions by
      connecting the DRE- and ERE-mediated signaling pathways. The results herein might
      promote the understanding of the mechanisms of specific DNA recognition and gene
      expression regulation by DREBs.

PMID- 18089557
TI  - Cripto is a noncompetitive activin antagonist that forms analogous signaling
      complexes with activin and nodal.
AB  - Cripto plays critical roles during embryogenesis and has been implicated in
      promoting the growth and spread of tumors. Cripto is required for signaling by
      certain transforming growth factor-beta superfamily members, such as Nodal, but
      also antagonizes others, such as activin. The opposing effects of Cripto on Nodal
      and activin signaling seem contradictory, however, because these closely related
      ligands utilize the same type I (ALK4) and type II (ActRII/IIB) receptors. Here,
      we have addressed this apparent paradox by demonstrating that Cripto forms
      analogous receptor complexes with Nodal and activin and functions as a
      noncompetitive activin antagonist. Our results show that activin-A and Nodal
      elicit similar maximal signaling responses in the presence of Cripto that are
      substantially lower than that of activin-A in the absence of Cripto. In addition,
      we provide biochemical evidence for complexes containing activin-A, Cripto, and
      both receptor types and show that the assembly of such complexes is competitively
      inhibited by Nodal. We further demonstrate that Nodal and activin-A share the
      same binding site on ActRII and that ALK4 has distinct and separable binding
      sites for activin-A and Cripto. Finally, we show that ALK4 mutants with disrupted
      activin-A binding retain Cripto binding and prevent the effects of Cripto on both
      activin-A and Nodal signaling. Together, our data indicate that Cripto
      facilitates Nodal signaling and inhibits activin signaling by forming receptor
      complexes with these ligands that are structurally and functionally similar.

PMID- 18089558
TI  - Fyn modulation of Dab1 effects on amyloid precursor protein and ApoE receptor 2
      processing.
AB  - Dab1 is an intracellular adaptor protein that interacts with amyloid precursor
      protein (APP) and apoE receptor 2 (apoEr2), increases their levels on the cell
      surface, and increases their cleavage by alpha-secretases. To investigate the
      mechanism underlying these alterations in processing and trafficking of APP and
      apoEr2, we examined the effect of Fyn, an Src family-tyrosine kinase known to
      interact with and phosphorylate Dab1. Co-immunoprecipitation, co-immunostaining,
      and fluorescence lifetime imaging demonstrated an association between Fyn and
      APP. Fyn induced phosphorylation of APP at Tyr-757 of the (757)YENPTY(762) motif
      and increased cell surface expression of APP. Overexpression of Fyn alone did not
      alter levels of sAPPalpha or cytoplasmic C-terminal fragments, although it
      significantly decreased production of Abeta. However, in the presence of Dab1,
      Fyn significantly increased sAPPalpha and C-terminal fragments. Fyn-induced APP
      phosphorylation and cell surface levels of APP were potentiated in the presence
      of Dab1. Fyn also induced phosphorylation of apoEr2 and increased its cell
      surface levels and, in the presence of Dab1, affected processing of its C
      terminal fragment. In vivo studies showed that sAPPalpha was decreased in the Fyn
      knock-out, supporting a role for Fyn in APP processing. These data demonstrate
      that Fyn, due in part to its effects on Dab1, regulates the phosphorylation,
      trafficking, and processing of APP and apoEr2.

PMID- 18089559
TI  - How interaction of perfringolysin O with membranes is controlled by sterol
      structure, lipid structure, and physiological low pH: insights into the origin of
      perfringolysin O-lipid raft interaction.
AB  - Perfringolysin O (PFO) is a sterol-dependent, pore-forming cytolysin. To
      understand the molecular basis of PFO membrane interaction, we studied its
      dependence upon sterol and lipid structure and aqueous environment. PFO
      interacted with diverse sterols, although binding was affected by double bond
      location in the sterol rings, sterol side chain structure, and sterol polar group
      structure. Importantly, a sterol structure promoting formation of ordered
      membrane domains (lipid rafts) was not critical for interaction. PFO membrane
      interaction was also affected by phospholipid acyl chain structure, being
      inversely related to tight acyl chain packing with cholesterol. Experiments using
      the pre-pore Y181A mutant demonstrated that sterol binding strength and
      specificity was not affected by whether PFO forms a transmembrane beta-barrel.
      Combined, these observations are consistent with a model in which the strength
      and specificity of sterol interaction arises from both sterol interactions with
      domain 4 and sterol chemical activity within membranes. The lipid raft-binding
      portions of sterol bound to PFO may remain largely exposed to the lipid bilayer.
      These results place important constraints upon the origin of PFO raft affinity.
      Additional experiments demonstrated that the structure of membrane-inserted PFO
      at low and neutral pH was similar as judged by the effect of phospholipid and
      sterol structure upon PFO properties and membrane interaction. However, low pH
      enhanced PFO membrane binding, oligomerization, and pore formation. In lipid
      vesicles mimicking the exofacial (outer) membrane leaflet, PFO-membrane binding
      was maximal at pH 5.5-6. This is consistent with the hypothesis that PFO function
      involves acidic vacuoles.

PMID- 18089561
TI  - A catalytically independent physiological function for human acute phase protein
      group IIA phospholipase A2: cellular uptake facilitates cell debris removal.
AB  - Human group IIA phospholipase A2 (IIA PLA2) is an acute phase protein first
      identified at high concentrations in synovial fluid from patients with rheumatoid
      arthritis. Its physiological role has since been debated; the enzyme has a very
      high affinity for anionic phospholipid interfaces but expresses almost zero
      activity with zwitterionic phospholipid substrates, because of a lack of
      interfacial binding. We have prepared the cysteine-containing mutant (S74C) to
      allow the covalent attachment of fluorescent reporter groups. We show that
      fluorescently labeled IIA was taken up by phorbol 12-myristate 13-acetate
      activated THP-1 cells in an energy-dependent process involving cell surface
      heparan sulfate proteoglycans. Uptake concurrently involved significant cell
      swelling, characteristic of macropinocytosis and the fluorescent enzyme localized
      to the nucleus. The endocytic process did not necessitate enzyme catalysis,
      ruling out membrane phospholipid hydrolysis as an essential requirement. The
      enzyme produced supramolecular aggregates with anionic phospholipid vesicles as a
      result of bridging between particles, a property that is unique to this globally
      cationic IIA PLA2. Uptake of such aggregates labeled with fluorescent anionic
      phospholipid was dramatically enhanced by the IIA protein, and uptake involved
      binding to heparan sulfate proteoglycans on activated THP-1 cells. A
      physiological role for this protein is proposed that involves the removal of
      anionic extracellular cell debris, including anionic microparticles generated as
      a result of trauma, infection, and the inflammatory response, and under such
      conditions serum levels of IIA PLA2 can increase approximately 1000-fold. A
      similar pathway may be significant in the uptake into cells of anionic vector DNA
      involving cationic lipid transfection protocols.

PMID- 18089560
TI  - S100A1 binds to the calmodulin-binding site of ryanodine receptor and modulates
      skeletal muscle excitation-contraction coupling.
AB  - S100A1, a 21-kDa dimeric Ca2+-binding protein, is an enhancer of cardiac Ca2+
      release and contractility and a potential therapeutic agent for the treatment of
      cardiomyopathy. The role of S100A1 in skeletal muscle has been less well defined.
      Additionally, the precise molecular mechanism underlying S100A1 modulation of
      sarcoplasmic reticulum Ca2+ release in striated muscle has not been fully
      elucidated. Here, utilizing a genetic approach to knock out S100A1, we
      demonstrate a direct physiological role of S100A1 in excitation-contraction
      coupling in skeletal muscle. We show that the absence of S100A1 leads to
      decreased global myoplasmic Ca2+ transients following electrical excitation.
      Using high speed confocal microscopy, we demonstrate with high temporal
      resolution depressed activation of sarcoplasmic reticulum Ca2+ release in S100A1
      /- muscle fibers. Through competition assays with sarcoplasmic reticulum vesicles
      and through tryptophan fluorescence experiments, we also identify a novel S100A1
      binding site on the cytoplasmic face of the intact ryanodine receptor that is
      conserved throughout striated muscle and corresponds to a previously identified
      calmodulin-binding site. Using a 12-mer peptide of this putative binding domain,
      we demonstrate low micromolar binding affinity to S100A1. NMR spectroscopy
      reveals this peptide binds within the Ca2+-dependent hydrophobic pocket of
      S100A1. Taken together, these data suggest that S100A1 plays a significant role
      in skeletal muscle excitation-contraction coupling, primarily through specific
      interactions with a conserved binding domain of the ryanodine receptor. This
      warrants further investigation into the use of S100A1 as a therapeutic target for
      the treatment of both cardiac and skeletal myopathies.

PMID- 18089562
TI  - Mechanism, regulation, and functional properties of Dictyostelium myosin-1B.
AB  - Myosin-1B is one of three long tailed class-1 myosins containing an ATP
      insensitive actin-binding site in the tail region that are produced in
      Dictyostelium discoideum. Myosin-1B localizes to actin-rich structures at the
      leading edge of migrating cells where it has been implicated in the formation and
      retraction of membrane projections, the recycling of plasma membrane components,
      and intracellular particle transport. Here, we have used a combination of
      molecular engineering approaches to describe the kinetic and motile properties of
      the myosin-1B motor and its regulation by TEDS site phosphorylation. Our results
      show that myosin-1B is a low duty ratio motor and displays the fastest nucleotide
      binding kinetics of any of the Dictyostelium class-1 myosins studied so far.
      Different from Dictyostelium myosin-1D and myosin-1E, dephosphorylated myosin-1B
      is not inactivated but moves actin filaments efficiently, albeit at an up to 8
      fold slower velocity in the in vitro motility assay. A further difference is that
      myosin-1B lacks the ability to switch between rapid movement and bearing tension
      upon physiological changes of free Mg2+ ions. In this respect, its motor
      properties appear to be more closely related to Dictyostelium myosin-2 and rabbit
      skeletal muscle myosin.

PMID- 18089563
TI  - Immediate-early signaling induced by E-cadherin engagement and adhesion.
AB  - Epithelial cell-cell interactions require localized adhesive interactions between
      E-cadherin on opposing membranes and the activation of downstream signaling
      pathways that affect membrane and actin dynamics. However, it is not known
      whether E-cadherin engagement and activation of these signaling pathways are
      locally coordinated or whether signaling is sustained or locally down-regulated
      like other receptor-mediated pathways. To obtain high spatiotemporal resolution
      of immediate-early signaling events upon E-cadherin engagement, we used laser
      tweezers to place beads coated with functional E-cadherin extracellular domain on
      cells. We show that cellular E-cadherin accumulated rapidly around beads,
      reaching a sustained plateau level in 1-3 min. Phosphoinositides and Rac1 co
      accumulated with E-cadherin, reached peak levels with E-cadherin, but then
      rapidly dispersed. Both E-cadherin and Rac1 accumulated independently of Rac1 GTP
      binding/hydrolysis, but these activities were required for Rac1 dispersal. E
      cadherin accumulation was dependent on membrane dynamics and actin
      polymerization, but actin did not stably co-accumulate with E-cadherin;
      mathematical modeling showed that diffusion-mediated trapping could account for
      the initial E-cadherin accumulation. We propose that initial E-cadherin
      accumulation requires active membrane dynamics and involves diffusion-mediated
      trapping at contact sites; to propagate further contacts, phosphatidylinositol 3
      kinase and Rac1 are transiently activated by E-cadherin engagement and initiate a
      new round of membrane dynamics, but they are subsequently suppressed at that site
      to allow maintenance of weak E-cadherin mediated adhesion.

PMID- 18089564
TI  - Mechanical stimulation of bone in vivo reduces osteocyte expression of
      Sost/sclerostin.
AB  - Sclerostin, the protein product of the Sost gene, is a potent inhibitor of bone
      formation. Among bone cells, sclerostin is found nearly exclusively in the
      osteocytes, the cell type that historically has been implicated in sensing and
      initiating mechanical signaling. The recent discovery of the antagonistic effects
      of sclerostin on Lrp5 receptor signaling, a crucial mediator of skeletal
      mechanotransduction, provides a potential mechanism for the osteocytes to control
      mechanotransduction, by adjusting their sclerostin (Wnt inhibitory) signal output
      to modulate Wnt signaling in the effector cell population. We investigated the
      mechanoregulation of Sost and sclerostin under enhanced (ulnar loading) and
      reduced (hindlimb unloading) loading conditions. Sost transcripts and sclerostin
      protein levels were dramatically reduced by ulnar loading. Portions of the ulnar
      cortex receiving a greater strain stimulus were associated with a greater
      reduction in Sost staining intensity and sclerostin-positive osteocytes (revealed
      via in situ hybridization and immunohistochemistry, respectively) than were lower
      strain portions of the tissue. Hindlimb unloading yielded a significant increase
      in Sost expression in the tibia. Modulation of sclerostin levels appears to be a
      finely tuned mechanism by which osteocytes coordinate regional and local
      osteogenesis in response to increased mechanical stimulation, perhaps via
      releasing the local inhibition of Wnt/Lrp5 signaling.

PMID- 18089565
TI  - Different mechanisms regulate lysophosphatidic acid (LPA)-dependent versus
      phorbol ester-dependent internalization of the LPA1 receptor.
AB  - Lysophosphatidic acid (LPA) stimulates cells by activation of five G-protein
      coupled receptors, termed LPA 1-5. The LPA 1 receptor is the most widely
      expressed and is a major regulator of cell migration. In this study, we show that
      phorbol ester (PMA)-induced internalization of the LPA(1) receptor requires
      clathrin AP-2 complexes, protein kinase C, and a distal dileucine motif (amino
      acids 352 and 353) in the cytoplasmic tail but not beta-arrestin. Agonist
      dependent internalization of LPA 1, however, requires a cluster of serine
      residues (amino acids 341-347) located proximal to the dileucine motif, beta
      arrestin, and to a lesser extent clathrin AP-2. The serine cluster of LPA 1 is
      required for beta-arrestin2-GFP translocation to the plasma membrane and signal
      desensitization. In contrast, the dileucine motif (IL) is required for both basal
      and PMA-induced internalization. Evidence for the beta-arrestin independence of
      PMA-induced internalization of LPA 1 comes from the observations that beta
      arrestin2-GFP is not recruited to the plasma membrane upon PMA treatment and that
      LPA 1 is readily internalized in beta-arrestin1/2 knock-out mouse embryonic
      fibroblasts. These results indicate that distinct molecular mechanisms regulate
      agonist-dependent and PMA-dependent internalization of the LPA 1 receptor.

PMID- 18089566
TI  - RAG-heptamer interaction in the synaptic complex is a crucial biochemical
      checkpoint for the 12/23 recombination rule.
AB  - In V(D)J recombination, the RAG1 and RAG2 protein complex cleaves the
      recombination signal sequences (RSSs), generating a hairpin structure at the
      coding end. The cleavage occurs only between two RSSs with different spacer
      lengths of 12 and 23 bp. Here we report that in the synaptic complex,
      recombination-activating gene (RAG) proteins interact with the 7-mer and unstack
      the adjacent base in the coding region. We generated a RAG1 mutant that exhibits
      reduced RAG-7-mer interaction, unstacking of the coding base, and hairpin
      formation. Mutation of the 23-RSS at the first position of the 7-mer, which has
      been reported to impair the cleavage of the partner 12-RSS, demonstrated
      phenotypes similar to those of the RAG1 mutant; the RAG interaction and base
      unstacking in the partner 12-RSS are reduced. We propose that the RAG-7-mer
      interaction is a critical step for coding DNA distortion and hairpin formation in
      the context of the 12/23 rule.

PMID- 18089567
TI  - MCL-1 inhibits BAX in the absence of MCL-1/BAX Interaction.
AB  - The BCL-2 family of proteins plays a major role in the control of apoptosis as
      the primary regulator of mitochondrial permeability. The pro-apoptotic BCL-2
      homologues BAX and BAK are activated following the induction of apoptosis and
      induce cytochrome c release from mitochondria. A second class of BCL-2
      homologues, the BH3-only proteins, is required for the activation of BAX and BAK.
      The activity of both BAX/BAK and BH3-only proteins is opposed by anti-apoptotic
      BCL-2 homologues such as BCL-2 and MCL-1. Here we show that anti-apoptotic MCL-1
      inhibits the function of BAX downstream of its initial activation and
      translocation to mitochondria. Although MCL-1 interacted with BAK and inhibited
      its activation, the activity of MCL-1 against BAX was independent of an
      interaction between the two proteins. However, the anti-apoptotic function of MCL
      1 required the presence of BAX. These results suggest that the pro-survival
      activity of MCL-1 proceeds via inhibition of BAX function at mitochondria,
      downstream of its activation and translocation to this organelle.

PMID- 18089568
TI  - Migration to apoptotic "find-me" signals is mediated via the phagocyte receptor
      G2A.
AB  - Phagocytosis of apoptotic cells is fundamentally important throughout life,
      because non-cleared cells become secondarily necrotic and release intracellular
      contents, thus instigating inflammatory and autoimmune responses. Secreted "find
      me" and exposed "eat-me" signals displayed by the dying cell in concert with the
      phagocyte receptors comprise the phagocytic synapse of apoptotic cell clearance.
      In this scenario, lysophospholipids (lysoPLs) are assumed to act as find-me
      signals for the attraction of phagocytes. However, both the identity of the lyso
      PLs released from apoptotic cells and the nature of the phagocyte receptor are
      largely unknown. By a detailed analysis of the structural requirements we show
      here that lysophosphatidylcholine (lysoPC), but none of the lysoPC metabolites or
      other lysoPLs, represents the essential apoptotic attraction signal able to
      trigger a phagocyte chemotactic response. Furthermore, using RNA interference and
      expression studies, we demonstrate that the G-protein-coupled receptor G2A,
      unlike its relative GPR4, is involved in the chemotaxis of monocytic cells. Thus,
      our study identifies lysoPC and G2A as the crucial receptor/ligand system for the
      attraction of phagocytes to apoptotic cells and the prevention of autoimmunity.

PMID- 18089569
TI  - Closing the gap on autosomal dominant connexin-26 and connexin-43 mutants linked
      to human disease.
AB  - Cells within the vast majority of human tissues communicate directly through
      clustered arrays of intercellular channels called gap junctions. Gene ablation
      studies in mouse models have revealed that these intercellular channels are
      necessary for a variety of organ functions and that some of these genes are
      essential for survival. Molecular genetics has uncovered that germ line mutations
      in nearly half of the genes that encode the 21-member connexin family of gap
      junction proteins are linked to one or more human diseases. Frequently, these
      mutations are autosomal recessive, whereas in other cases, autosomal dominant
      mutations manifest as disease. Given the broad and overlapping distribution of
      connexins in a wide arrangement of tissues, it is hard to predict where connexin
      linked diseases will clinically manifest. For instance, the most prevalent
      connexin in the human body is connexin-43 (Cx43), yet autosomal dominant
      mutations in the GJA1 gene, which encodes Cx43, exhibit modest developmental
      disorders resulting in a disease termed oculodentodigital dysplasia. Autosomal
      recessive mutations in the gene encoding Cx26 result in moderate to severe
      sensorineural hearing loss, whereas autosomal dominant mutations produce hearing
      loss and a wide range of skin diseases, including palmoplantar keratoderma. Here,
      we will focus on autosomal dominant mutations of the genes encoding Cx26 and Cx43
      in relation to models that link genotypes to phenotypic outcomes with particular
      reference to how these approaches provide insight into human disease.

PMID- 18089570
TI  - Structural determinants of calmodulin binding to the intracellular C-terminal
      domain of the metabotropic glutamate receptor 7A.
AB  - Calmodulin (CaM) binds in a Ca2+-dependent manner to the intracellular C-terminal
      domains of most group III metabotropic glutamate receptors (mGluRs). Here we
      combined mutational and biophysical approaches to define the structural basis of
      CaM binding to mGluR 7A. Ca2+/CaM was found to interact with mGluR 7A primarily
      via its C-lobe at a 1:1 CaM:C-tail stoichiometry. Pulldown experiments with
      mutant CaM and mGluR 7A C-tail constructs and high resolution NMR with peptides
      corresponding to the CaM binding region of mGluR 7A allowed us to define
      hydrophobic and ionic interactions required for Ca2+/CaM binding and identified a
      1-8-14 CaM-binding motif. The Ca2+/CaM.mGluR 7A peptide complex displays a
      classical wraparound structure that closely resembles that formed by Ca2+/CaM
      upon binding to smooth muscle myosin light chain kinase. Our data provide insight
      into how Ca2+/CaM regulates group III mGluR signaling via competition with
      intracellular proteins for receptor-binding sites.

PMID- 18089571
TI  - Purification and properties of the vaccinia virus mRNA processing factor.
AB  - The mRNAs encoding the vaccinia virus F17 protein and the cowpox A-type inclusion
      protein are known to possess sequence-homogeneous 3' ends, generated by a post
      transcriptional cleavage event. By using partially purified extracts, we have
      previously shown that the same factor probably cleaves both the F17 and A-type
      inclusion protein transcripts and that the cleavage factor is either virus-coded
      or virus-induced during the post-replicative phase of virus replication. In this
      study, we have purified the cleavage factor from vaccinia-infected HeLa cells
      using column chromatography and gel filtration. The factor eluted from the gel
      filtration column with an apparent molecular mass of approximately 440 kDa. Mass
      spectrometric analyses of the proteins present in the peak active fractions
      revealed the presence of at least one vaccinia protein with a high degree of
      certainty, the H5R gene product. To extend this finding, extracts were prepared
      from HeLa cells infected with vaccinia virus overexpressing His-tagged H5,
      chromatographed on a nickel affinity column, and eluted using an imidazole
      gradient. Cleavage activity eluted with the peak of His-tagged H5. Gel filtration
      of the affinity-purified material further demonstrated that cleavage activity and
      His-tagged H5 co-chromatographed with an apparent molecular mass of 463 kDa. We
      therefore conclude that H5 is specifically associated with post-transcriptional
      cleavage of F17R transcripts. In addition, we show that dephosphorylation of a
      cleavage competent extract with a nonspecific phosphatase abolishes cleavage
      activity implying a role for phosphorylation in cleavage activity.

PMID- 18089572
TI  - The Psb27 protein facilitates manganese cluster assembly in photosystem II.
AB  - Photosystem II (PSII) is a large membrane protein complex that uses light energy
      to convert water to molecular oxygen. This enzyme undergoes an intricate assembly
      process to ensure accurate and efficient positioning of its many components. It
      has been proposed that the Psb27 protein, a lumenal extrinsic subunit, serves as
      a PSII assembly factor. Using a psb27 genetic deletion strain (Deltapsb27) of the
      cyanobacterium Synechocystis sp. PCC 6803, we have defined the role of the Psb27
      protein in PSII biogenesis. While the Psb27 protein was not essential for
      photosynthetic activity, various PSII assembly assays revealed that the
      Deltapsb27 mutant was defective in integration of the Mn(4)Ca(1)Cl(x) cluster,
      the catalytic core of the oxygen-evolving machinery within the PSII complex. The
      other lumenal extrinsic proteins (PsbO, PsbU, PsbV, and PsbQ) are key components
      of the fully assembled PSII complex and are important for the water oxidation
      reaction, but we propose that the Psb27 protein has a distinct function separate
      from these subunits. We show that the Psb27 protein facilitates Mn(4)Ca(1)Cl(x)
      cluster assembly in PSII at least in part by preventing the premature association
      of the other extrinsic proteins. Thus, we propose an exchange of lumenal subunits
      and cofactors during PSII assembly, in that the Psb27 protein is replaced by the
      other extrinsic proteins upon assembly of the Mn(4)Ca(1)Cl(x) cluster.
      Furthermore, we show that the Psb27 protein provides a selective advantage for
      cyanobacterial cells under conditions such as nutrient deprivation where
      Mn(4)Ca(1)Cl(x) cluster assembly efficiency is critical for survival.

PMID- 18089573
TI  - Monocyte chemoattractant protein-1 expression is enhanced by granulocyte
      macrophage colony-stimulating factor via Jak2-Stat5 signaling and inhibited by
      atorvastatin in human monocytic U937 cells.
AB  - The proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM
      CSF) is expressed in inflammatory and atherosclerotic lesions. GM-CSF is known to
      enhance monocytic expression of monocyte chemoattractant protein-1 (MCP-1).
      However, the molecular mechanism(s) by which GM-CSF up-regulates the MCP-1
      expression remains to be clarified. Thus, in this study, we examined our
      hypothesis that GM-CSF up-regulates the MCP-1 expression via Jak2-Stat5 signaling
      pathway. In human monocytic cell line U937, GM-CSF increased MCP-1 expression in
      protein and mRNA levels. Furthermore, analysis of the GM-CSF promoter element
      revealed that the STAT5 (signal transducer and activator of transcription-5)
      transcription factor binding site, located between -152 and -144 upstream of the
      transcription start site, as well as Janus kinase-2-mediated Stat5 activation
      were necessary for the GM-CSF-induced transcriptional up-regulation of the MCP-1
      gene. This GM-CSF-induced MCP-1 expression, measured as both protein and mRNA
      levels, was down-regulated by atorvastatin, a 3-hydroxy-3-methylglutaryl-CoA
      reductase inhibitor. However, this decrease in MCP-1 expression was not at the
      transcriptional level of MCP-1 gene but rather at the level of the stability of
      MCP-1 mRNA. These results indicate that GM-CSF regulates MCP-1 expression via
      Janus kinase-2-Stat5 pathway and by a novel regulatory mechanism of statins to
      reduce inflammatory reactions by down-regulating the expression of monocytic MCP
      1, which promotes atherogenesis.

PMID- 18089574
TI  - Mycobacterium tuberculosis CYP130: crystal structure, biophysical
      characterization, and interactions with antifungal azole drugs.
AB  - CYP130 is one of the 20 Mycobacterium tuberculosis cytochrome P450 enzymes, only
      two of which, CYP51 and CYP121, have so far been studied as individually
      expressed proteins. Here we characterize a third heterologously expressed M.
      tuberculosis cytochrome P450, CYP130, by UV-visible spectroscopy, isothermal
      titration calorimetry, and x-ray crystallography, including determination of the
      crystal structures of ligand-free and econazole-bound CYP130 at a resolution of
      1.46 and 3.0A(,) respectively. Ligand-free CYP130 crystallizes in an "open"
      conformation as a monomer, whereas the econazole-bound form crystallizes in a
      "closed" conformation as a dimer. Conformational changes enabling the "open
      closed" transition involve repositioning of the BC-loop and the F and G helices
      that envelop the inhibitor in the binding site and reshape the protein surface.
      Crystal structure analysis shows that the portion of the BC-loop relocates as
      much as 18A between the open and closed conformations. Binding of econazole to
      CYP130 involves a conformational change and is mediated by both a set of
      hydrophobic interactions with amino acid residues in the active site and
      coordination of the heme iron. CYP130 also binds miconazole with virtually the
      same binding affinity as econazole and clotrimazole and ketoconazole with
      somewhat lower affinities, which makes it a plausible target for this class of
      therapeutic drugs. Overall, binding of the azole inhibitors is a sequential two
      step, entropy-driven endothermic process. Binding of econazole and clotrimazole
      exhibits positive cooperativity that may reflect a propensity of CYP130 to
      associate into a dimeric structure.

PMID- 18089575
TI  - Structural and functional analysis of the Spt16p N-terminal domain reveals
      overlapping roles of yFACT subunits.
AB  - yFACT (heterodimers of Saccharomyces cerevisiae Spt16-Pob3 combined with Nhp6)
      binds to and alters the properties of nucleosomes. The essential function of
      yFACT is not disrupted by deletion of the N-terminal domain (NTD) of Spt16 or by
      mutation of the middle domain of Pob3, but either alteration makes yeast cells
      sensitive to DNA replication stress. We have determined the structure of the
      Spt16 NTD and find evidence for a conserved potential peptide-binding site. Pob3
      M also contains a putative binding site, and we show that these two sites perform
      an overlapping essential function. We find that yFACT can bind the N-terminal
      tails of some histones and that this interaction is important for yFACT
      nucleosome binding. However, neither the Spt16 NTD nor a key residue in the
      putative Pob3-M-binding site was required for interactions with histone N termini
      or for yFACT-mediated nucleosome reorganization in vitro. Instead, both potential
      binding sites interact functionally with the C-terminal docking domain of the
      histone H2A. yFACT therefore appears to make multiple contacts with different
      sites within nucleosomes, and these interactions are partially redundant with one
      another. The docking domain of H2A is identified as an important participant in
      maintaining stability during yFACT-mediated nucleosome reorganization, suggesting
      new models for the mechanism of this activity.

PMID- 18089576
TI  - Yeast antizyme mediates degradation of yeast ornithine decarboxylase by yeast but
      not by mammalian proteasome: new insights on yeast antizyme.
AB  - Mammalian antizyme (mAz) is a central element of a feedback circuit regulating
      cellular polyamines by accelerating ornithine decarboxylase (ODC) degradation and
      inhibiting polyamine uptake. Although yeast antizyme (yAz) stimulates the
      degradation of yeast ODC (yODC), we show here that it has only a minor effect on
      polyamine uptake by yeast cells. A segment of yODC that parallels the Az binding
      segment of mammalian ODC (mODC) is required for its binding to yAz. Although
      demonstrating minimal homology to mAz, our results suggest that yAz stimulates
      yODC degradation via a similar mechanism of action. We demonstrate that
      interaction with yAz provokes degradation of yODC by yeast but not by mammalian
      proteasomes. This differential recognition may serve as a tool for investigating
      proteasome functions.

PMID- 18089577
TI  - Work area measurements as predictors of personal exposure to endotoxin and cotton
      dust in the cotton textile industry.
AB  - OBJECTIVES: To determine if work area measurements of endotoxin and/or cotton
      dust obtained from the vertical elutriator (VE) can be used to predict levels of
      personal endotoxin exposure as measured by the Institute of Occupational Medicine
      (IOM) inhalable dust sampler in the cotton textile industry. METHODS: Fifty-six
      work area cotton dust samples were collected from 14 areas and 82 personal cotton
      dust samples were collected from 41 workers in three textile mills (Mills A, B
      and C) in Shanghai, China. Cotton dust concentrations were determined
      gravimetrically from sample filters, of which endotoxin concentrations were
      determined using a kinetic chromogenic modification of the limulus amoebocyte
      lysate assay. Linear regression models were used to determine the association
      between log IOM personal endotoxin concentration and log VE area endotoxin
      concentration. RESULTS: Median cotton dust and endotoxin concentrations measured
      from VE area samples in the three mills were 0.36 mg m(-3) and 1280.76 endotoxin
      units per cubic meter (EU m(-3)), respectively, compared to 1.74 mg m(-3) and
      2226.83 EU m(-3) from IOM personal samples. Excluding samples from weaving
      processes, we observed linear associations between VE area measures of endotoxin
      and IOM personal endotoxin concentrations; VE area concentration of endotoxin
      explained 83 and 89% of the total variation in IOM personal endotoxin
      concentration for Mills A and B, respectively (Mill A: R2 = 0.83, P < 0.0001;
      Mill B: R2 = 0.89, P < 0.0001). Although area measures of cotton dust was also a
      significant predictor of person endotoxin, the model explained less of the
      variance in personal endotoxin measurements. CONCLUSIONS: Specific to the
      conditions of the textile mills investigated in this study, work area
      measurements of endotoxin, but not cotton dust, may be reasonable proxies for
      personal levels, at least for rank-ordering exposures.

PMID- 18089579
TI  - Fundamental requirements for primary visual perception.
AB  - A novel perspective for the necessary and sufficient conditions for primary
      visual perception is proposed based upon relating recent discoveries from the
      visual sciences to relevant foundational neurological observations. This analysis
      suggests that a fundamental requirement for the emergence of normal primary
      visual perception is the coupling between the early visual cortices in the
      occipital lobe subserving image content with specific areas in the parietal lobe
      subserving selective attention, representations of extrapersonal space, the body
      schema, and the initiation of perceptual ownership. Fully intact primary visual
      perception, which includes the normal placement of image content within
      extrapersonal space, seems to require at each instant a mutually consistent
      completeness and corresponding removal of ambiguities in each of the linked
      neural representations subserving image, space and self. Experimental approaches
      that could either invalidate or strengthen the proposed framework are suggested
      as well as opportunities to differentiate some aspects of normal primary visual
      perception from the severely compromised visual experience that survives
      bilateral parieto-occipital lesions (Balint's syndrome) when visual experience
      may persist for single but unlocalizable objects.

PMID- 18089578
TI  - Mapping the relationship between cortical convolution and intelligence: effects
      of gender.
AB  - The pronounced convolution of the human cortex may be a morphological substrate
      that supports some of our species' most distinctive cognitive abilities.
      Therefore, individual intelligence within humans might be modulated by the degree
      of folding in certain cortical regions. We applied advanced methods to analyze
      cortical convolution at high spatial resolution and correlated those measurements
      with intelligence quotients. Within a large sample of healthy adult subjects (n =
      65), we detected the most prominent correlations in the left medial hemisphere.
      More specifically, intelligence scores were positively associated with the degree
      of folding in the temporo-occipital lobe, particularly in the outermost section
      of the posterior cingulate gyrus (retrosplenial areas). Thus, this region might
      be an important contributor toward individual intelligence, either via modulating
      pathways to (pre)frontal regions or by serving as a location for the convergence
      of information. Prominent gender differences within the right frontal cortex were
      observed; females showed uncorrected significant positive correlations and males
      showed a nonsignificant trend toward negative correlations. It is possible that
      formerly described gender differences in regional convolution are associated with
      differences in the underlying architecture. This might lead to the development of
      sexually dimorphic information processing strategies and affect the relationship
      between intelligence and cortical convolution.

PMID- 18089580
TI  - Investigation of loss and gain of introns in the compact genomes of pufferfishes
      (Fugu and Tetraodon).
AB  - We have investigated intron evolution in the compact genomes of 2 closely related
      species of pufferfishes, Fugu rubripes and Tetraodon nigroviridis, that diverged
      about 32 million years ago (MYA). Analysis of 148,028 aligned intron positions in
      13,547 gene pairs using human as an outgroup identified 57 and 24 intron losses
      in Tetraodon and fugu lineages, respectively, and no gain in either lineage. For
      comparison, we analyzed 144,545 intron positions in 12,866 orthologous pairs of
      genes in human and mouse that diverged about 61 MYA using dog as an outgroup and
      identified 51 intron losses in mouse and 3 losses in human and no gain. The rate
      of intron loss in Tetraodon is higher than that in fugu, mouse, and human but
      lower than the previous estimates for other eukaryotes. The introns lost in
      pufferfishes and mammals are significantly shorter than the mean size of introns
      in the genome. One intron deleted in fugu and another in Tetraodon have left
      behind 6 and 3 nucleotides, respectively, suggesting that they were lost due to
      genomic deletions. Such losses of introns are likely to be the result of a higher
      rate of DNA deletions experienced by the genomes of pufferfishes compared with
      mammals. The shorter generation time of Tetraodon compared with fugu, and the
      rich diversity and higher activity of transposable elements in pufferfishes
      compared with mammals, may be responsible for the higher rate of intron loss in
      Tetraodon. Our findings indicate that overall very little intron turnover has
      occurred in pufferfishes and mammals during recent evolution and that intron gain
      is an extremely rare event in vertebrate evolution.

PMID- 18089581
TI  - Differences in the metabolite profiles of spinach (Spinacia oleracea L.) leaf in
      different concentrations of nitrate in the culture solution.
AB  - The nitrogen (N) status of a plant determines the composition of its major
      components (amino acids, proteins, carbohydrates and organic acids) and, directly
      or indirectly, affects the quality of agricultural products in terms of their
      calorific value and taste. Although these effects are guided by changes in
      metabolic pathways, no overall metabolic analysis has previously been conducted
      to demonstrate such effects. Here, metabolite profiling using gas chromatography
      mass spectrometry (GC-MS) was used to evaluate the effect of N levels on spinach
      tissue, comparing two cultivars that differed in their ability to use N. Wide
      variation in N content was observed without any distinct inhibition of growth in
      either cultivar. Principal component analysis (PCA) and self-organizing mapping
      (SOM) were undertaken to describe changes in the metabolites of mature spinach
      leaves. In PCA, the first component accounted for 44.5% of the total variance,
      the scores of which was positively correlated with the plant's N content, and a
      close relationship between metabolite profiles and N status was observed. Both
      PCA and SOM revealed that metabolites could be broadly divided into two types,
      correlating either positively or negatively with plant N content. The simple and
      co-coordinated metabolic stream, containing both general and spinach-specific
      aspects of plant N content, will be useful in future research on such topics as
      the detection of environmental effects on spinach through comprehensive metabolic
      profiling.

PMID- 18089582
TI  - Its evolution in Platanus (Platanaceae): homoeologues, pseudogenes and ancient
      hybridization.
AB  - BACKGROUND AND AIMS: Platanaceae is an old family of angiosperms extending back
      to the Early Cretaceous but consisting of a single extant genus, Platanus.
      Species of Platanus have long been known to hybridize, and the London plane,
      Platanus x hispanica, is a well-known example of a hybrid species that formed in
      historical times. In addition, morphological studies have suggested past
      interspecific or interlineage hybridization and reticulation as possibly
      important factors in the evolution of the genus. This study aims at unravelling
      the complex evolutionary information contained in internal transcribed spacer
      (ITS) sequences. METHODS: The ITS of the 35S nuclear ribosomal DNA are
      biparentally inherited, multi-copy markers with a high potential for resolving
      intrageneric relationships especially when ancient hybridization (reticulation)
      is involved. Phylogenetic trees, splits graphs and motif analysis are used to
      extract phylogenetic information from 223 cloned ITS sequences, representing ten
      species and varieties of Platanus. Non-pseudogenous and pseudogenous sequence
      motives are assessed to explain how different evolutionary modes contribute to
      possibly conflicting character state patterns in the ITS. KEY RESULTS: It was
      found that putative non-functional ITS copies ('pseudogenes') form distinct
      groups in phylograms and splits graphs, and that pseudogenous lineages reflect
      ancient hybridization events conserved in the ITS. Specifically, pseudogenous
      clones of an 'Atlantic' North American clade share sequence motives with non
      pseudogenous clones of the western ('Pacific') North American P. racemosa species
      aggregate. In addition, evidence was found for recent lateral gene flow as a
      possible factor in the evolution of the central Mexican P. rzedowskii.
      CONCLUSIONS: Broad ITS data sets that cover intra- and interindividual
      variability reveal past and ongoing speciation processes in Platanus.
      Evolutionary pathways can be visualized with splits graphs, but not with
      bifurcating trees.

PMID- 18089583
TI  - Inequality of size and size increment in Pinus banksiana in relation to stand
      dynamics and annual growth rate.
AB  - BACKGROUND AND AIMS: Changes in size inequality in tree populations are often
      attributed to changes in the mode of competition over time. The mode of
      competition may also fluctuate annually in response to variation in growing
      conditions. Factors causing growth rate to vary can also influence competition
      processes, and thus influence how size hierarchies develop. METHODS: Detailed
      data obtained by tree-ring reconstruction were used to study annual changes in
      size and size increment inequality in several even-aged, fire-origin jack pine
      (Pinus banksiana) stands in the boreal shield and boreal plains ecozones in
      Saskatchewan and Manitoba, Canada, by using the Gini and Lorenz asymmetry
      coefficients. KEY RESULTS: The inequality of size was related to variables
      reflecting long-term stand dynamics (e.g. stand density, mean tree size and
      average competition, as quantified using a distance-weighted absolute size
      index). The inequality of size increment was greater and more variable than the
      inequality of size. Inequality of size increment was significantly related to
      annual growth rate at the stand level, and was higher when growth rate was low.
      Inequality of size increment was usually due primarily to large numbers of trees
      with low growth rates, except during years with low growth rate when it was often
      due to small numbers of trees with high growth rates. The amount of competition
      to which individual trees were subject was not strongly related to the inequality
      of size increment. CONCLUSIONS: Differences in growth rate among trees during
      years of poor growth may form the basis for development of size hierarchies on
      which asymmetric competition can act. A complete understanding of the dynamics of
      these forests requires further evaluation of the way in which factors that
      influence variation in annual growth rate also affect the mode of competition and
      the development of size hierarchies.

PMID- 18089584
TI  - Cytosolic nitrate ion homeostasis: could it have a role in sensing nitrogen
      status?
AB  - BACKGROUND AND AIMS: question of whether homeostasis occurs for some nutrients
      and, if so, what are the consequences for how plants sense their nutrient status.
      Particularly for nitrate, this controversy has focused on the methods used and
      the cellular pools which they measure. Cytoplasm and cytosol have been
      distinguished and it has been suggested that two ranges of nitrate values can be
      separated depending on whether the method separates the pools found in
      organelles. SCOPE: The present study defines homeostasis of nutrient ions and
      discusses how whole organ averaging techniques can hide important cellular
      differences that can help to explain some of the discrepancies between results
      reported by various methods. These results are considered in relation to a
      possible role in signalling nutrient status, and have relevance to other
      averaging techniques such as the use of 'omics' technologies.

PMID- 18089585
TI  - Data quality of 5 years of central norovirus outbreak reporting in the European
      Network for food-borne viruses.
AB  - BACKGROUND: The food-borne viruses in Europe (FBVE) network database was
      established in 1999 to monitor trends in outbreaks of gastroenteritis due to
      noroviruses (NoVs), to identify major transmission routes of NoV infections
      within and between participating countries and to detect diffuse international
      food-borne outbreaks. METHODS: We reviewed the total of 9430 NoV outbreak reports
      from 13 countries with date of onset between 1 January 2002 and 1 January 2007
      for representativeness, completeness and timeliness against these objectives.
      RESULTS: Rates of reporting ranged from a yearly average of 1.8 in 2003 to 11.6
      in 2006. Completeness of reporting of an agreed minimum dataset improved over the
      years, both for epidemiological and virological data. For the 10 countries that
      provided integrated (epidemiological AND virological) reporting over the 5-year
      period, the completeness of the minimum dataset rose from 15% in 2003 to 48% in
      2006. Two countries have not been able to combine both data types due to the
      structure of the national surveillance system (England and Wales and Germany).
      Timeliness of reporting (median days between the onset of an outbreak and the
      date of reporting to the FBVE database) differed greatly between countries, but
      gradually improved to 47 days in 2006. CONCLUSION: The outbreaks reported to the
      FBVE reflect the lack of standardization of surveillance systems across Europe,
      making direct comparison of data between countries difficult. However, trends in
      reported outbreaks per country, distribution of NoV genotypes, and detection of
      diffuse international outbreaks were used as background data in acute questions
      about NoV illness and the changing genotype distribution during the 5-year
      period, shown to be of added value. Integrated reporting is essential for these
      objectives, but could be limited to sentinel countries with surveillance systems
      that allow this integration. For successful intervention in case of diffuse
      international outbreaks, completeness and timeliness of reporting would need to
      be improved and expanded to countries that presently do not participate.

PMID- 18089586
TI  - Expression levels of mRNA for Rho A/Rho kinase and its role in isoprostane
      induced vasoconstriction of human placental and maternal vessels.
AB  - Preeclampsia is characterized by intense and prolonged vasoconstriction. Rho A
      mediated calcium sensitization is central to prolonged contractility of vascular
      smooth muscle. The aims of this study are (1) to investigate mRNA expression
      levels of Rho A/Rho kinases in placental tissues from normotensive and
      preeclamptic women and (2) to investigate the effects of 2 isoprostanes, 8-iso
      prostaglandin F(2)( alpha) (8-iso PGF(2 alpha) ) and 8-iso prostaglandin E(2) (8
      iso PGE(2)), on small placental and myometrial vessel resistance and to determine
      if their effects were mediated via the Rho kinase pathway. Real-time reverse
      transcription polymerase chain reaction for Rho A, ROCK I, and ROCK II was
      performed on total RNA from normotensive and preeclamptic placentae. The effects
      of 8- iso PGF(2 alpha) and 8-iso PGE(2) (alone and with the specific Rho kinase
      inhibitor Y-27632) on placental and myometrial vessels (<400 microm) were
      measured and compared with control recordings. Rho A mRNA expression levels were
      significantly higher in placentae from preeclamptic women than in placentae from
      normotensive women (P < .01). There was no significant difference in expression
      levels of ROCK I and ROCK II between both tissue types (P > .05). Both
      isoprostanes exerted a significant concentration-dependent vasocontractile effect
      on both vessel types (P < .001). This effect was antagonized by Y-27632 in
      placental arteries but not in myometrial arteries. Increased Rho A mRNA
      expression in placentae from preeclamptic women is suggestive of a role for the
      Rho kinase pathway in the modulation of the placental vasculature in this
      condition. Isoprostanes exert their vasocontractile effect, in placental
      vasculature, in part via the Rho kinase pathway.

PMID- 18089587
TI  - Interleukin-1 beta secretion from cord blood mononuclear cells in vitro involves
      P2X 7 receptor activation.
AB  - The purinergic receptor P2X(7) is activated by extracellular adenosine 5'
      triphosphate (ATP) and promotes the efficient release of interleukin-1 beta. The
      authors examine protein and molecular expression of the P2X(7) receptor and its
      ability to stimulate interleukin-1 beta release in cord blood mononuclear cells
      (CBMCs) from placentae of term nonlaboring and laboring women. They show both
      mRNA and protein (78 kDa) expression for the P2X( 7) receptor in CBMCs of
      parturient and nonparturient women. Costimulation of CBMCs in vitro with
      bacterial endotoxin and ATP resulted in significantly (P < .05) enhanced
      interleukin-1 beta release in laboring (54.17 +/- 24.78 pg/mL(-1); n = 8)
      compared with nonlaboring (13.60 +/- 3.20 pg/mL(-1); n = 7) deliveries. Release
      of interleukin-1 beta in both groups was blocked by preincubation with oxidized
      ATP, a P2X(7) receptor antagonist. The authors provide evidence for a novel
      inflammatory pathway in the release of interleukin-1 beta, which may be linked to
      the onset of labor.

PMID- 18089588
TI  - Progesterone-mediated regulation of catechol-O-methyl transferase expression in
      endometrial cancer cells.
AB  - The effects of estrogen and progesterone on the expression of estrogen
      metabolizing enzymes such as catechol-O-methyl transferase (COMT) are not known.
      COMT converts genotoxic catecholestrogens to anticarcinogenic methoxyestrogens in
      the endometrium. The aim of this study is to investigate the effect of
      progesterone on COMT expression in well-differentiated endometrial cancer cells.
      The wild-type Ishikawa cell line as well as progesterone receptor A- or
      progesterone receptor B-transfected Ishikawa cells were used for in vitro
      studies. The regulation of COMT expression by progesterone was studied using
      Western blots, Hoechst dye DNA proliferation studies, and wild-type and/or site
      directed mutagenesis of COMT promoter 1-luciferase reporter gene. Progesterone
      upregulated COMT protein expression in Ishikawa cells through progesterone
      receptor A isoform. COMT promoter activity was differentially regulated by the 3
      half-site progesterone response elements in the COMT promoter. High doses of 2
      ME2 inhibited Ishikawa cell proliferation. These data suggest that COMT
      expression is hormonally regulated in well-differentiated human endometrial
      cancer cells. COMT regulation and 2-ME2 production in the endometrium may affect
      endometrial carcinogenesis.

PMID- 18089589
TI  - Expression of stem and germ cell markers within nonfollicle structures in adult
      mouse ovary.
AB  - Recent studies have suggested that germline stem cells may generate new follicles
      in the adult murine ovary. In this study, the authors use a pou5f1-enhanced green
      fluorescent protein (EGFP) transgenic mouse model to study the expression of stem
      and germ cell markers in adult murine ovaries. Immunohistochemical analyses and
      reverse transcription polymerase chain reaction were performed to detect the
      expression of mouse vasa homologue, stem cells factor receptor, stage-specific
      embryonic antigen 1, synaptonemal complex proteins, disrupted meiotic, and growth
      differentiation factor-9 in GFP+ ovarian tissues. GFP+ cell aggregates of
      nonfollicle structures were identified and isolated from adult B6.CBA-Tg(pou5f1
      EGFP)2Mnn/J transgenic mouse ovaries. This study shows the presence of cell
      aggregates that are distinct from ovarian follicles and are coexpressing germline
      and stem cell surface markers in adult murine ovaries. These cell aggregates may
      represent a mixed population of germ cells and germline stem cells. Further
      research is necessary to evaluate the plasticity of the potential stem cell
      population in these cell aggregates.

PMID- 18089591
TI  - Commentary.

PMID- 18089592
TI  - Gonadotropin-releasing hormone in the ovary.
AB  - Gonadotropin-releasing hormone (GnRH) plays a pivotal role in the physiology of
      reproduction in mammals. GnRH acts by binding to the GnRH receptor (GnRHR). In
      humans, only 1 conventional GnRH receptor subtype (type I GnRH receptor) has been
      found. In the human genome, 2 forms of GnRH have been identified, GnRH-I (mammal
      GnRH) and GnRH-II (chicken GnRH II). Both forms and their common receptor are
      expressed, apart from the hypothalamus, in various compartments of the human
      ovary. Gonadal steroids, gonadotropins, and GnRH itself controls the regulation
      of the GnRH/GnRHR system gene expression in the human ovary. The 2 types of GnRH
      acting paracrinally/autocrinally influence ovarian steroidogenesis, decrease the
      proliferation, and induce apoptosis of ovarian cells. In this review, the biology
      of GnRH/GnRHR system in humans, the potential roles of GnRH, and the direct
      effects of GnRH analogues in ovarian cells are discussed.

PMID- 18089593
TI  - Dose-dependent effects of meloxicam administration on cyclooxygenase-1 and
      cyclooxygenase-2 protein expression in intrauterine tissues and fetal tissues of
      a sheep model of preterm labor.
AB  - Meloxicam (MEL), a cyclooxygenase (COX)-2 inhibitor, decreases prostaglandin
      production and blocks preterm labor in sheep. The objective of this study is to
      investigate MEL dosage regimens on COX-1, COX-2, and prostaglandin dehydrogenase
      (PGDH) expression in ovine intrauterine and fetal tissues. Animals in preterm
      labor received maternal infusions of saline or MEL at maintained high or graded
      doses (study 1) or acute graded doses (study 2). MEL blocked preterm labor. In
      study 1, MEL decreased COX-2 expression in the endometrium, myometrium, and
      amnion but not placenta or fetal tissues. In study 2, COX-2 expression was
      unchanged. COX-1/PGDH expression was unaffected. While MEL is an effective
      tocolytic, reductions in COX-2 protein occurred only with maintained MEL
      exposure. MEL effects are tissue specific and do not affect COX-1 or PGDH
      expression. Maternal MEL does not affect fetal COX expression in the sheep,
      possibly contributing to its lack of fetal side effects.

PMID- 18089594
TI  - Endothelium-dependent vasodilatation in formerly preeclamptic women correlates
      inversely with body mass index and varies independently of plasma volume.
AB  - Endothelial dysfunction and a subnormal plasma volume predispose to preeclampsia.
      The authors determine whether endothelium-dependent vasodilatation is lower in
      formerly preeclamptic women, explore whether endothelial dysfunction coincides
      with low plasma volume, and determine if endothelial dysfunction correlates with
      circulating endothelial stressors. In formerly preeclamptic women and controls,
      the authors estimated changes in forearm blood flow after arterial occlusion.
      They measured plasma volume, blood pressure, and circulating variables. To
      identify factors associated with endothelial function, the authors used Spearman
      correlation and regression analysis. Endothelial function did not differ between
      patients and controls and did not correlate with plasma volume; however, it did
      correlate negatively with body mass index and positively with arterial
      compliance. Analysis suggested a negative impact of metabolic syndrome on
      endothelial function. In formerly preeclamptic women, endothelial function is
      comparable to controls and varies independently of plasma volume. In patients,
      endothelial function does vary with features of the metabolic syndrome.

PMID- 18089595
TI  - Pregnancy enhances the prejunctional vasodilator response to adrenomedullin in
      selective regions of the arterial bed of Wistar rats.
AB  - The objective of this study is to determine whether the vascular response to
      adrenomedullin is modulated by pregnancy. To this end, the authors study the
      effect of adrenomedullin on different contractile responses of mesenteric,
      uterine, renal, and saphenous arteries of 10-day pregnant and nonpregnant rats in
      myographs. Adrenomedullin inhibited contractile responses induced by electrical
      field stimulation in only the mesenteric and uterine arteries. This effect was
      more pronounced during pregnancy than in the nonpregnant state. Adrenomedullin
      did not modify concentration response curves to noradrenaline. The reduction of
      contractile responses to 40 mmol/L K(+) by adrenomedullin was similar in arteries
      of pregnant and nonpregnant rats. However, after incubation with capsaicin, this
      effect was significantly increased in mesenteric arteries of the pregnant group.
      The authors conclude that pregnancy is associated with a rise in the
      prejunctional inhibitory effect of adrenomedullin in some regions of the arterial
      system.

PMID- 18089596
TI  - Heterozygosity for the classical galactosemia mutation does not affect ovarian
      reserve and menopausal age.
AB  - Female patients with classical galactosemia (galactose-1-phosphate
      uridyltransferase [GALT] deficiency) frequently suffer from premature ovarian
      failure, despite treatment with a galactose-restricted diet. Earlier research has
      suggested an association between heterozygosity for GALT mutations and early
      menopause. This study evaluates the effect of carriership for classical
      galactosemia on ovarian reserve and menopausal age. Proven female carriers of
      classical galactosemia were recruited via the Dutch Galactosemia Society. All 58
      participants underwent a structured interview regarding fertility, smoking
      status, and menopause. To determine ovarian reserve, 42 premenopausal GALT
      carriers underwent ovarian antral follicle count (AFC) by transvaginal ultrasound
      and early follicular phase blood sampling for hormonal measurement of follicle
      stimulating hormone (FSH), inhibin B, and anti-Mullerian hormone (AMH). These
      ovarian reserve parameters were compared with a cohort of proven fertile women (n
      = 166). The mean age at menopause in GALT carriers was 49.7 years, which is not
      different from the mean age at menopause in the general population in the
      Netherlands. There was no difference in FSH, inhibin B, and AMH levels or in the
      AFC (when corrected for age and smoking status) between 42 premenopausal GALT
      carriers and controls. The authors conclude that there is no evidence that GALT
      mutation carriership affects ovarian reserve or menopausal age.

PMID- 18089597
TI  - Relation of daily urinary hormone patterns to vasomotor symptoms in a
      racially/ethnically diverse sample of midlife women: study of women's health
      across the nation.
AB  - The associations of urinary pregnanediol-glucuronide (PdG) levels and menstrual
      bleeding and their modification of associations of other risk factors with
      vasomotor symptoms (VMS) are examined. Daily urine samples were collected for 1
      menstrual cycle or 50 days if no bleeding occurred. Participants (n = 742) were
      aged 43 to 54 years, not using exogenous hormones, not pregnant, had an intact
      uterus and > 1 ovary, and menstruated in the prior 3 months. Multivariate
      analyses were performed of urinary hormone metabolites and within-woman
      proportion of days reporting VMS. VMS reporting was 4-fold greater (P = .0005) in
      women whose urine collections ended without bleeding. In collections with PdG
      levels suggestive of ovulatory activity according to the work of Kassam et al,
      VMS are significantly associated with obesity, early perimenopause, and
      increasing PdG levels. In collections with lower PdG concentrations, VMS are
      significantly increased with no bleeding, smoking, higher age, physical activity,
      follicle-stimulating hormone, and luteinizing hormone and are significantly
      reduced with increasing estrogen concentrations.

PMID- 18089598
TI  - Expression of aromatase and estrogen sulfotransferase in eutopic and ectopic
      endometrium: evidence for unbalanced estradiol production in endometriosis.
AB  - Endometriosis is an estrogen-dependent gynecological disease causing pelvic pain
      and infertility. Impaired estrogen metabolism is thought to play a pivotal role
      in the pathogenesis of the disease. While there is some information on factors
      involved in the synthesis of E2, information on E2-deactivating enzymes is still
      very limited. To elucidate the intracrinology of endometriotic tissues, the
      authors analyze the expression of aromatase and E2-inactivating estrogen
      sulfotransferase (EST) in paired biopsies obtained simultaneously from the
      endometrium and from endometrial lesions of each of 35 patients with peritoneal
      or ovarian endometriosis and in cycling endometria from 33 women without
      endometriosis. Protein localization was demonstrated by immunohistochemistry.
      Aromatase expression was found in endometriotic glands in 32 of 35 cases and was
      elevated in comparison to corresponding uterine endometria (25 of 35 cases, P =
      .021, chi(2) test). The difference was even more pronounced when uterine
      endometria from endometriosis patients were compared with that of healthy
      controls (8 of 33 cases, P < .001, chi(2) test). The EST levels were essentially
      unchanged. The elevated expression of aromatase in eutopic and ectopic
      endometrium from patients with endometriosis in the presence of comparable EST
      provides further evidence for unopposed local biosynthesis of estrogens in
      endometriosis.

PMID- 18089599
TI  - Type-specific antiviral antibodies to genital human papillomavirus types in
      mothers and newborns.
AB  - Type-specific antibodies to human papillomaviruses (HPVs) can be detected in most
      infected adult patients, and they have virus-neutralizing properties. However,
      there is a dearth of information on the seroprevalence of maternal and neonatal
      antibodies to HPV capsid antigens. Sera from 104 mothers, their newborns, and 3
      twin pregnancies were analyzed by an enzyme-linked immunosorbent assay (ELISA)
      for the presence of specific IgG, IgM, and IgA antibodies to virus-like particles
      of HPV-6, -11, -16, -18, and -31. Maternal IgG positivity rates to HPV types 6,
      11, 16, 18, and 31 were 23.1%, 2.9%, 8.7%, 5.8%, and 9.6%, respectively. Neonatal
      rates did not differ significantly, and individual IgG ELISA values of mothers
      and their infants and all paired twins showed a very high correlation. In
      contrast, nearly all IgM and IgA individual values in newborns were designated
      negative, whereas mothers' positivity rates ranged as high as 19.2%. Infants
      showed no HPV-related lesions at birth or at 4-year follow-up. Seven of 8 tested
      children lost IgG HPV antibodies in a follow-up examination. Similar anti-HPV IgG
      seropositivity in mothers and newborns and a lack of neonatal IgA and IgM
      together with twin and follow-up results indicate that neonatal IgG is not a sign
      of intrauterine HPV infection but, rather, maternofetal antibody transmission.

PMID- 18089600
TI  - Experimental endometriosis in the rat is correlated with colonic motor function
      alterations but not with bacterial load.
AB  - Endometriosis commonly presents with symptoms that mimic chronic gastrointestinal
      disorders. The authors used the autotransplantion model of endometriosis in rats
      to investigate the possible underlying mechanisms. After the rats were killed,
      the presence of endometriotic vesicles, colonic inflammation, and white blood
      cell (WBC) numbers in the peritoneal fluid was determined. Sections of colon and
      of jejunum were collected for measurement of myeloperoxidase (MPO) activity and
      bacterial counts, and isometric recording in response to acetylcholine was
      measured in segments of longitudinal and circular smooth muscle. Experimental
      animals had significantly more colonic damage, MPO activity, and WBC numbers than
      controls did. There was no significant difference in the total bacterial load;
      however, experimental animals demonstrated an increased tension in the
      longitudinal muscle, which correlated with WBC numbers and colonic damage. In
      summary, this study presents evidence for a significant effect of peritoneal
      endometriosis on colonic function and integrity, which may help explain the
      gastrointestinal symptoms associated with this disease.

PMID- 18089601
TI  - The broad-spectrum chemokine inhibitor NR58-3.14.3 suppresses the implantation
      and survival of human endometrial implants in the nude mice endometriosis model.
AB  - Many chemokines likely contribute to the pathogenesis of endometriosis. The
      authors hypothesize that the broad-spectrum chemokine inhibitor NR58-3.14.3 may
      prevent ectopic human endometrium implantation and growth. After placing human
      endometrium fragments into the peritoneal cavity, ovariectomized athymic nude
      mice (n = 31) receiving intramuscular estradiol valerate were randomly assigned
      to daily intraperitoneal injections of either phosphate-buffered saline or NR58
      3.14.3. Fourteen days later, the implant number and volume, proliferating cell
      nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase (TdT)-mediated
      dUTP nick end-labeling (TUNEL) index, and MTT cell viability were assessed in the
      implants. NR58-3.14.3 reduced the total number (45%) and total volume (81%) of
      endometriotic lesions (P < .05) and revealed a lower PCNA and higher TUNEL index
      in ectopic implants compared with controls (P < .05). NR58-3.14.3 treatment did
      not affect endometrial cell proliferation in vitro. NR58-3.14.3, by possibly
      regulating cell survival, can reduce the number and size of ectopic implants in
      vivo, supporting the potential use of chemokine inhibitors in novel therapies for
      endometriosis.

PMID- 18089602
TI  - Metastin stimulates aldosterone synthesis in human adrenal cells.
AB  - Kisspeptins, including metastin, are encoded by the KiSS-1 gene and play an
      important role in regulating the hypothalamic gonadotropin-releasing hormone
      (GnRH) system via G protein-coupled receptor 54 (GPR54, also called KiSS-1R).
      Normally, metastin (also called Kp-54) levels are quite low, except during
      pregnancy, when levels increase 1000-fold over those found in men and nonpregnant
      women. However, the potential hormonal role of metastin in the fetal and maternal
      circulation is unknown. In this study, the authors examine the levels of GPR54
      mRNA expression in human adult and fetal adrenals using quantitative real-time
      reverse-transcriptase polymerase chain reaction (RT-PCR). In addition, they
      examine the effects of metastin on steroidogenesis and steroidogenic enzyme mRNA
      levels in fetal adrenal cells and in the H295R adrenocortical cell line using
      enzyme immunoassay and RT-PCR techniques. The authors demonstrate that GPR54 mRNA
      is significantly higher (50-fold) in human fetal adrenals than in adult adrenals.
      Immunohistochemical studies have demonstrated that the GPR54 protein is
      predominantly expressed in the neocortex of human fetal adrenals in the third
      trimester. Metastin increases aldosterone production (approximately 2-fold) in
      both fetal neocortex adrenal cells and H295R adrenal cells, with a maximal
      increase seen at 100 nM. In addition, metastin increased angiotensin II (Ang II)
      stimulated aldosterone production by approximately 1.5-fold. Metastin also
      increased the ability of the H295R cells to metabolize exogenously added
      pregnenolone to aldosterone but had no effect on the expression of aldosterone
      synthase (CYP11B2). These results suggest that the high fetal/maternal levels of
      metastin seen during pregnancy may affect adrenal production of aldosterone.

PMID- 18089604
TI  - The role of the extracellular matrix in ovarian follicle development.
AB  - Regulation of ovarian follicle development depends on endocrine- and paracrine
      acting hormones, the 3-dimensional architecture of the follicle, and the physical
      rigidity of the surrounding tissue. These 3 forces are integrated throughout the
      life cycle of the follicle to ensure appropriate hormone secretion,
      differentiation of the somatic cells, and maturation of the oocyte. The process
      of in-follicle maturation provides a new tool for understanding ovarian follicle
      development under the influence of these factors.

PMID- 18089605
TI  - Three-dimensional cell culture to model epithelia in the female reproductive
      system.
AB  - In vitro 3-dimensional (3D) cell cultures produce valuable models that mimic 3D
      tissue organization and function and enhance the understanding of cell/tissue
      function under normal and pathological situations. Tissue function depends on the
      interactions between cells and the extracellular matrix; thus, effective 3D cell
      cultures rely on the use of appropriate extracellular matrix cues. Noticeable
      progress in 3D cell culture was obtained from studies with epithelial cells from
      organs of the female reproductive system including the mammary glands, the
      uterus, and the ovaries. These models show that replicating normal tissue
      organization in the resting phase is a prerequisite for appropriate physiological
      and pathological investigations. The authors' goals are to explain the importance
      of mimicking detailed aspects of normal epithelial organization and function,
      such as basoapical polarity, in 3D cell culture and to discuss how effective 3D
      cell culture models can lead to meaningful applications in reproductive biology.

PMID- 18089606
TI  - Comparative effects of SPRM asoprisnil (J867) on proliferation, apoptosis, and
      the expression of growth factors in cultured uterine leiomyoma cells and normal
      myometrial cells.
AB  - Progesterone plays a pivotal role in controlling uterine leiomyoma growth. The
      authors review studies they conducted to evaluate the comparative effects of
      asoprisnil on proliferation, apoptosis, and growth factor expression in cultured
      leiomyoma and normal myometrial cells. Treatment with asoprisnil decreased the
      proliferating cell nuclear antigen-positive rate and the number of viable cells
      and increased the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine
      5'-triphosphate nick end labeling- positive rate in cultured leiomyoma cells in a
      dose-dependent manner ( P < .05). Similarly, asoprisnil decreased Bcl-2
      expression and increased cleaved caspase-3 and cleaved poly(adenosine 5'
      diphosphate-ribose) polymerase in leiomyoma cells but not in normal myometrial
      cells. Similarly, asoprisnil decreased epidermal growth factor (EGF), insulin
      like growth factor-I (IGF-I), and transforming growth factor (TGF) beta mRNA and
      protein expression, as well as EGF receptor, IGF-IR alpha, and TGF RII protein
      expression in leiomyoma cells but not in cultured normal myometrial cells. These
      results suggest that asoprisnil selectively inhibits proliferation by
      downregulating the growth factors and their receptor expression and induces
      apoptosis in leiomyoma cells without affecting proliferation and apoptosis in
      normal myometrial cells.

PMID- 18089607
TI  - Vascular remodeling and extracellular matrix breakdown in the uterine spiral
      arteries during pregnancy.
AB  - During pregnancy, trophoblasts invade and transform the maternal spiral arteries
      that supply blood to the placenta. Recent work has revealed that this process
      occurs in several stages, and details of the molecular and cellular mechanisms
      are beginning to emerge, including changes that precede or accompany
      trophoblastic colonization of the vascular media. Disruption and eventual loss of
      smooth muscle cells and their associated extracellular matrix are central to
      physiological transformation. Advances in understanding will lead to the
      identification of the causative factors involved in failure of remodeling in
      pathological pregnancies and suggest novel diagnostic and therapeutic avenues.

PMID- 18089608
TI  - Stretching, mechanotransduction, and proinflammatory cytokines in the fetal
      membranes.
AB  - In the third trimester of normal pregnancy, the human fetal membranes become
      increasingly distended and use mechanotransduction and its downstream signaling
      to remodel and function. Their overdistension either by multifetal pregnancy or
      by polyhydramnios often leads to preterm birth, but the mechanism is unclear.
      Stretching of the fetal membranes in vitro upregulates several cytokines and
      enzymes that can drive collagen degradation, leading to membrane rupture. The
      sensitivity of this response appears to be specific for different cell types and
      is likely to result from differential activation of some key transcription
      factors and cofactors. Few cytokines in the fetal membranes respond to stretch:
      the most robust of these is pre-B-cell colony-enhancing factor (PBEF). This is
      constitutively expressed and protects the amnion cells from apoptosis caused by
      chronic static distension. However, it can also be stimulated by inflammation,
      infection, and hypoxia and upregulates a number of proinflammatory cytokines,
      chemokines, and enzymes important in the initiation of parturition. Therefore, it
      is proposed here that PBEF functions in normal pregnancy to protect the amnion
      cells as they become increasingly stretched, but if stimulated, it can initiate
      key events leading to parturition.

PMID- 18089609
TI  - Relaxin and the human fetal membranes.
AB  - The human fetal membranes are complex tissues that perform many important
      functions during gestation. The extracellular matrix provides their strength to
      withstand the forces directed from the fetus and myometrium. Relaxin is a
      collagenolytic hormone that causes increased production of the matrix
      metalloproteinases. Its expression from the decidua is increased in patients with
      preterm premature rupture of the membranes, and its leucine-rich G receptor 7 is
      upregulated at preterm. The authors previously showed that relaxin is not
      involved in the infection-mediated cytokine response, but in the absence of
      infection, it causes increased secretion of both interleukin -6 and interleukin-8
      from the membranes. In this article, the authors propose that relaxin is one of a
      number of sterile stimuli capable of causing increased proinflammatory cytokines,
      similar to but less robust than the effects of infection. These probably
      represent distinct inflammatory pathways involving different intracellular
      signaling events, which can result in either preterm premature rupture of the
      membranes or preterm labor. The current challenge is to fully understand these
      pathways and to clarify their similarities and differences.

PMID- 18089610
TI  - The circulating proangiogenic factors CYR61 (CCN1) and NOV (CCN3) are
      significantly decreased in placentae and sera of preeclamptic patients.
AB  - It is thought that preeclampsia results from a shallow invasion of the
      extravillous trophoblast into the decidua and maternal vessels, which in turn
      leads to hypoxia and uteroplacental insufficiency. Here, the authors focus on the
      expression of the proangiogenic secreted molecules CYR61 (CCN1) and NOV (CCN3) in
      human placentae during normal pregnancy compared with preeclamptic placentae.
      CYR61 and NOV are strongly expressed in endothelial cells as well as in the
      extravillous trophoblast, with increasing levels during placental development.
      Interestingly, the authors found significantly decreased levels in early
      preeclamptic placentae compared with matched controls. Whereas both CYR61 and NOV
      proteins are present at constant high levels in the sera of nonpregnant and
      pregnant women, in the sera of patients with early-onset preeclampsia, levels
      were significantly reduced. The authors suggest that the reduction of both CCN
      molecules in preeclampsia could be 1 reason underlying the failure of uterine
      vascular remodeling. Moreover, their low maternal serum levels could serve as
      biomarkers for early diagnosis of this disease.

PMID- 18089611
TI  - Processes regulating cervical ripening differ from cervical dilation and
      postpartum repair: insights from gene expression studies.
AB  - A greater understanding of the processes that regulate cervical remodeling during
      pregnancy, parturition, and the postpartum period is required to understand
      causes of preterm and posterm birth in which abnormal cervical function is the
      primary culprit. In the current study, gene expression patterns unique to
      cervical ripening as compared with cervical dilation and/or postpartum repair are
      identified in a mouse model. Genes differentially regulated from gestation day 15
      to late day 18 reveal processes important for cervical ripening. Genes
      differentially regulated from late day 18 to 2 hours after birth reveal processes
      that could be important during cervical dilation or the postpartum recovery
      period. Based on expression patterns, cervical ripening requires a downregulation
      of collagen assembly genes; increased synthesis of glycosaminoglycans that
      disrupt the matrix, such as hyaluronan; increased metabolism of progesterone; and
      changes in epithelial barrier properties. The latter phases of dilation and
      postpartum recovery are associated with increased assembly of mature collagen,
      synthesis of matrix proteins that promote a dense connective tissue, activation
      of inflammatory responses, prostaglandin synthesis, and further changes in
      epithelial barrier properties and differentiation. Processes/gene expression
      required for cervical ripening are distinct from those important in latter phases
      of cervical remodeling and highlight the importance of timing of tissue
      collection for understanding the molecular mechanisms of cervical ripening.

PMID- 18089612
TI  - Thrombospondin-1 and thrombospondin-2 mRNA and TSP-1 and TSP-2 protein expression
      in uterine fibroids and correlation to the genes COL1A1 and COL3A1 and to the
      collagen cross-link hydroxyproline.
AB  - Uterine fibroids are composed of altered collagen fibrils and represent an
      arrested response to injury-initiating fibrosis. In many tissues, TSP-1 is
      secreted by adult macrophages and monocytes upon wounding and is involved in the
      activation of transforming growth factor beta. In the absence of TSP-1, the
      orchestrated process of wound healing is impaired. The authors obtained tissue
      from the edge and center of fibroids at the time of hysterectomy and compared
      them with adjacent myometrium. The pattern of TSP-1 and TSP-2 expression was
      correlated to that of COL1A1 and COL3A1. Collagen and hydroxyproline were
      increased in fibroids. Thrombospondin-1 was consistently underexpressed in both
      the edge and center of the fibroids, while COL1A1 and COL3A1 were consistently
      overexpressed. However, TSP-2 was inconsistently expressed. These findings lead
      to the conclusion that the underexpression of TSP-1 may contribute to the overall
      development of uterine fibroids.

PMID- 18089613
TI  - Expression of pulmonary vasoactive factors after sevoflurane anaesthesia in rats:
      a quantitative real-time polymerase chain reaction study.
AB  - BACKGROUND: Sevoflurane is a fluorinated volatile anaesthetic agent that lowers
      arterial pressure, in part by vasodilation. We previously showed, in rat lungs,
      that sevoflurane affected the expression of endothelin-1 (ET-1), a potent
      vasoconstrictor peptide. Therefore, we hypothesized that the vasodilation induced
      by sevoflurane involved vasodilatory and vasoconstrictor components. METHODS:
      Rats were anaesthetized with sevoflurane 4% for 0, 2, and 6 h (n=9 each group)
      before death. In addition, a further group (n=9) were anaesthetized for 6 h then
      awoken for 2 h before death (n=9). We measured expression of mRNA encoding ET-1,
      nitric oxide synthase-1, 2, 3 (NOS1, 2, 3), haeme oxygenase-1, 2 (HO-1, 2),
      adrenomedullin (ADM), calcitonin gene-related peptide, vasoactive intestinal
      peptide, and prostacyclin synthase in whole lung using real-time reverse
      transcriptase-polymerase chain reaction. RESULTS: Expressions of ET-1 and ADM
      were significantly increased by inhalation of sevoflurane for 2 and 6 h (P<0.05).
      Expression of NOS3 was significantly increased at 6 h (P<0.05). After awaking
      from anaesthesia, the expressions of NOS3, ET-1, and ADM returned to baseline
      levels. CONCLUSIONS: Sevoflurane increased the expressions of ET-1, NOS3, and
      ADM. Our results suggest that the increased expressions of NOS3 and ADM may
      counteract that of ET-1 and so regulate pulmonary circulation under sevoflurane
      anaesthesia.

PMID- 18089614
TI  - Parity and the use of out-of-network mental health benefits in the FEHB program.
AB  - Two current congressional bills mandate parity for benefits for mental disorders
      with benefits for medical/surgical conditions in private insurance when mental
      health benefits are provided; the bills differ in regard to benefit levels and
      access to out-of-network coverage. This study assessed clinicians' and
      beneficiaries' participation in managed care networks in the national capital
      area under the Federal Employees Health Benefits (FEHB) parity program.
      Approximately one-third of the clinicians studied participated in FEHB networks,
      and only 44 percent of FEHB patients received care from network clinicians. Out
      of-network mental health benefits are an important policy consideration to ensure
      access to mental health treatment under parity proposals.

PMID- 18089615
TI  - Perforation of the ascending aorta with a hematoma extending into the left-side
      upper extrapleural cavity.
AB  - We herein present an extremely rare case of a perforation of the ascending aorta
      with a hematoma extending into the left-side upper extrapleural cavity. A 62-year
      old male with a sudden onset of severe chest pain was referred to our institution
      because of an abnormal shadow in the left-side upper lung field. Computed
      tomography revealed a small fusiform aortic arch aneurysm and a hematoma
      extending to the left-side upper extrapleural cavity. We diagnosed the patient to
      have acute aortic syndrome and urgent surgery was thus performed. Major bleeding
      which might be caused by a progression of the perforation was seen during a
      dissection of the aorta. The aortic arch was transected and a total arch
      replacement was performed with a 26 mm Dacron graft. No findings of a rupture of
      the aortic arch aneurysm or dissection were observed. The histopathology of the
      aorta revealed a severe atheromatous lesion with calcification and thinning
      disarrayed elastic fibers. The postoperative course was essentially good except
      for the development of pericardial effusion which required drainage.

PMID- 18089616
TI  - Propranolol: a new indication for an old drug in preventing postoperative
      junctional ectopic tachycardia after surgical repair of tetralogy of Fallot.
AB  - Junctional ectopic tachycardia (JET) is a major cause of postoperative morbidity
      after complete repair of tetralogy of Fallot (TOF). Propranolol is a known
      medication used in patients with TOF to prevent and control hypercyanotic spells.
      Despite this, there is little information regarding the relation between
      preoperative use of propranolol and the incidence of postoperative JET. The aim
      of this study was to examine the effect of preoperative use of propranolol on the
      incidence of postoperative JET after full surgical repair of TOF. A retrospective
      analysis of 109 patients in whom 57 patients received preoperative propranolol
      (propranolol group) was compared with 52 patients who did not receive propranolol
      preoperatively (control group). The incidence of postoperative JET was
      significantly higher in the control group (38%) than the propranolol group (21%)
      P=0.042. The propranolol group had significantly less mechanical ventilation
      time, less ICU stay and less total hospital stay than the control group (P<0.05).
      Our findings suggest that the preoperative use of propranolol may decrease the
      incidence of JET after full surgical repair of TOF. A prospective randomized
      study may help to elucidate the exact relationship between the preoperative use
      of propranolol and the incidence of postoperative JET.

PMID- 18089617
TI  - CD30 supports lung inflammation.
AB  - The physiological functions of CD30 have not been fully elucidated. Here we show
      that in CD30-deficient mice (CD30(-/-)), lung inflammation is significantly
      diminished in the ovalbumin (OVA) model of airway hyperreactivity. In CD30(-/-)
      mice, the recruitment of eosinophils into the airways after OVA-aerosol challenge
      of OVA-primed mice was significantly diminished when compared with wild-type
      (w.t.) mice. IL-13 levels were also significantly reduced in CD30(-/-) mice while
      levels of IFN-gamma, IL-4, IL-5 and IgE in bronchoalveolar lavage fluid, lung
      tissue and serum were comparable to w.t. mice. Peribronchial lymph node cells
      from CD30(-/-) mice, re-stimulated in vitro with OVA, secreted significantly
      lower levels of IL-13 than those from w.t. mice, but showed normal proliferative
      response and other cytokine production. Exogenous IL-13 reconstituted airway
      recruitment of leukocytes in OVA-challenged CD3O(-/-) mice. Adoptive transfer to
      naive w.t. mice of in vitro OVA-re-stimulated spleen cells from CD30(-/-) mice
      failed to induce eosinophilic pulmonary inflammation in contrast to transfer of
      primed cells from w.t. mice. These results indicate that CD30 is a regulator of
      T(h)2 responses in the effector-memory phase and a regulator of IL-13 production
      in memory cells in the lung.

PMID- 18089618
TI  - Structural flexibility in proteins: impact of the crystal environment.
AB  - MOTIVATION: In the study of the structural flexibility of proteins,
      crystallographic Debye-Waller factors are the most important experimental
      information used in the calibration and validation of computational models, such
      as the very successful elastic network models (ENMs). However, these models are
      applied to single protein molecules, whereas the experiments are performed on
      crystals. Moreover, the energy scale in standard ENMs is undefined and must be
      obtained by fitting to the same data that the ENM is trying to predict, reducing
      the predictive power of the model. RESULTS: We develop an elastic network model
      for the whole protein crystal in order to study the influence of crystal packing
      and lattice vibrations on the thermal fluctuations of the atom positions. We use
      experimental values for the compressibility of the crystal to establish the
      energy scale of our model. We predict the elastic constants of the crystal and
      compare with experimental data. Our main findings are (1) crystal packing
      modifies the atomic fluctuations considerably and (2) thermal fluctuations are
      not the dominant contribution to crystallographic Debye-Waller factors.
      AVAILABILITY: The programs developed for this work are available as supplementary
      material at Bioinformatics Online.

PMID- 18089619
TI  - ZFIQ: a software package for zebrafish biology.
AB  - Rapid development, transparency and small size are the outstanding features of
      zebrafish that make it as an increasingly important vertebrate system for
      developmental biology, functional genomics, disease modeling and drug discovery.
      Zebrafish has been regarded as ideal animal specie for studying the relationship
      between genotype and phenotype, for pathway analysis and systems biology.
      However, the tremendous amount of data generated from large numbers of embryos
      has led to the bottleneck of data analysis and modeling. The zebrafish image
      quantitator (ZFIQ) software provides streamlined data processing and analysis
      capability for developmental biology and disease modeling using zebrafish model.
      AVAILABILITY: ZFIQ is available for download at http://www.cbi-platform.net.

PMID- 18089620
TI  - A novel genome-scale repeat finder geared towards transposons.
AB  - MOTIVATION: Repeats are ubiquitous in genomes and play important roles in
      evolution. Transposable elements are a common kind of repeat. Transposon
      insertions can be nested and make the task of identifying repeats difficult.
      RESULTS: We develop a novel iterative algorithm, called Greedier, to find repeats
      in a target genome given a repeat library. Greedier distinguishes itself from
      existing methods by taking into account the fragmentation of repeats. Each
      iteration consists of two passes. In the first pass, it identifies the local
      similarities between the repeat library and the target genome. Greedier then
      builds graphs from this comparison output. In each graph, a vertex denotes a
      similar subsequence pair. Edges denote pairs of subsequences that can be
      connected to form higher similarities. In the second pass, Greedier traverses
      these graphs greedily to find matches to individual repeat units in the repeat
      library. It computes a fitness value for each such match denoting the similarity
      of that match. Matches with fitness values greater than a cutoff are removed, and
      the rest of the genome is stitched together. The similarity cutoff is then
      gradually reduced, and the iteration is repeated until no hits are returned from
      the comparison. Our experiments on the Arabidopsis and rice genomes show that
      Greedier identifies approximately twice as many transposon bases as those found
      by cross_match and WindowMasker. Moreover, Greedier masks far fewer false
      positive bases than either cross_match or WindowMasker. In addition to masking
      repeats, Greedier also reports potential nested transposon structures.

PMID- 18089621
TI  - Significance of cardiac autonomic neuropathy in risk stratification of Brugada
      syndrome.
AB  - AIMS: Risk stratification in Brugada syndrome (BS) is controversial especially in
      asymptomatic individuals. The aim of this study was to evaluate the significance
      of cardiac autonomic neuropathy (CAN) in BS. METHODS AND RESULTS: Patients
      diagnosed with Brugada ECG pattern were enrolled in the study. Four standard
      cardiac autonomic function tests were performed. The presence of >or=2 abnormal
      test results were considered definite evidence for the presence of CAN. Types 1,
      2, and 3 Brugada ECG pattern were found in 28, 56, and 31 patients, respectively.
      CAN was detected in 13 (46%) patients with type 1 Brugada ECG pattern. In
      contrast, none of the type 2 or 3 Brugada patients had CAN. Of 13 patients with
      CAN, 11 had previous history of cardiac events (84%), whereas only 2 of 15
      patients without CAN had history of previous cardiac events (13%; P = 0.01). The
      most noteworthy finding was that all of the type 1 Brugada patients with CAN were
      male (CAN was not detected in females). CONCLUSIONS: It was concluded that CAN is
      an important risk indicator in BS. CAN is more common in men. Male gender, per
      se, is not an independent risk factor for development of ventricular arrhythmia
      but also CAN, which is an important risk factor in BS, is more common in men;
      therefore men are susceptible to the development of cardiac events.

PMID- 18089622
TI  - Glucocorticoid resistance in dialysis patients may impair the kidney allograft
      outcome.
AB  - This study examines in vitro steroid sensitivity in chronic renal failure (CRF)
      patients and its influence on the allograft outcome. We determined the inhibitory
      effect of dexamethasone (DEX) on concanavalin A (Con-A)-stimulated peripheral
      blood mononuclear cell (PBMC) proliferation, and glucocorticoid receptor' (GR)
      number of binding sites (B(max)) and affinity (K(d)) in 28 CRF patients and 40
      normal healthy controls. Based on K(d) values >95th percentile from controls,
      patients were divided into two groups: glucocorticoid resistant (n = 11) and
      glucocorticoid sensitive (n = 17). Patients were followed during 18 months post
      transplantation observing acute rejection episodes (ARE), chronic allograft
      nephropathy (CAN), allograft failure and death. The DEX concentration that caused
      50% inhibition of Con-A-stimulated PBMC proliferation (IC(50)) was higher in CRF
      than in healthy controls (2.2 x 10(-5) +/- 1.0 x 10(-5) versus 8.3 x 10(-6) +/-
      4.2 x 10(-6) mol/L, P = 0.02). Values of K(d) (12.4 +/- 1.8 versus 7.2 +/- 0.9
      nM) and B(max) (7.7 +/- 1.1 versus 4.1 +/- 0.3 fmol/mg protein) were higher in
      CRF patients (P = 0.02 and P = 0.001, respectively). There were higher incidences
      of ARE (P = 0.02) and CAN (P = 0.002) in the glucocorticoid-resistant group.
      Univariate and multivariate logistic regression showed that K(d) was an
      independent predictor of ARE (OR 8.8, P = 0.03) as well as of CAN (OR 16.5, P =
      0.01). In conclusion, we observed glucocorticoid resistance in a subgroup of CRF
      patients undergoing dialysis, which led to a higher morbidity due to ARE and CAN
      in an 18-month follow-up period.

PMID- 18089623
TI  - Effects of sulodexide in patients with type 2 diabetes and persistent
      albuminuria.
AB  - BACKGROUND: Urinary albumin excretion frequently persists in diabetic patients
      who are treated with angiotensin-converting enzyme inhibitors (ACEI) or
      angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of
      80% heparan sulfate and 20% dermatan sulfate, has been hypothesized to reduce
      persistent albuminuria. We have conducted a multi-center randomized double-blind
      pilot study in order to determine the effect of 6 months' therapy with sulodexide
      on urinary albumin excretion and to address logistical issues for a full-scale
      trial. METHODS: A total of 149 patients with type 2 diabetes and an
      albumin:creatinine ratio (ACR) between 20 and 300 mg/g were randomized with equal
      allocation to either placebo, 200 mg of sulodexide or 400 mg of sulodexide. The
      primary endpoint was the achievement, at 6 months, of either 3(1) return to
      normoalbuminuria (ACR < 20 mg/g with a decrease of at least 25%) or (2) a
      decrease in ACR of at least 50% from the baseline value. All patients used a
      maximum tolerated recommended FDA approved dose of an ACEI or ARB for at least 60
      days and had stable blood pressure prior to randomization. RESULTS: The primary
      efficacy endpoint was achieved in 25.3% of the patients in the two sulodexide
      groups combined versus 15.4% of the placebo-treated patients (P = 0.26). The
      primary endpoint was achieved in 33.3% (P = 0.075 for the comparison to placebo)
      in the sulodexide 200 mg group and 18.4% (P = 0.781) in the sulodexide 400 mg
      group. (No consistent patterns of side effects were observed. CONCLUSION: Based
      on the experience gained in this pilot study, one full-scale trial is currently
      being conducted to evaluate the effects of sulodexide on change in ACR in
      patients with persistent microalbuminuria, and a longer-term trial is underway to
      evaluate the effects of sulodexide on long-term renal disease progression in
      patients with overt proteinuria.

PMID- 18089624
TI  - Diagnostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for
      left ventricular dysfunction in patients with chronic kidney disease stage 5 on
      haemodialysis.
AB  - BACKGROUND: Natriuretic peptides such as N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) have become increasingly important in diagnosing left
      ventricular dysfunction (LVD), however, in patients with chronic kidney disease
      (CKD), their use is confounded by concomitant volume overload and reduced renal
      excretion. We hypothesized that a serum NT-proBNP cut-off value adjusted for
      patients with CKD could serve as a biochemical marker to detect LVD in patients
      on haemodialysis treatment regardless of chronic fluid overload. METHODS: We
      assessed LV function using trans-thoracic echocardiography and indices of
      hydration status such as extracellular water (ECW) using bioelectrical impedance
      analysis (BIA) in 62 stable patients on maintenance haemodialysis. NT-proBNP
      cutoff values for LVD with different specificities and sensitivities were
      calculated by ROC curves. RESULTS: We found a significant inverse correlation
      between LV ejection fraction (EF) and NT-proBNP levels (r = -0.77, P < 0.0001).
      In the multivariate regression analysis NT-proBNP was the only independent
      predictor of EF (r = 0.699, P < 0.0001). NT-proBNP levels were significantly
      higher (P < 0.0001) in patients with LVD (n = 15; 32 760 +/- 6605 ng/L) compared
      to those without LVD (n = 47; 2835 +/- 428 ng/L). An NT-proBNP cut-off value of
      7168 ng/L resulted in 90% specificity and 79% sensitivity for the presence of
      LVD, i.e. an EF <45% (AUC(ROC): 0.95 +/- 0.03, P < 0.0001). Furthermore, in
      patients with LVD we found a significant relationship between serum NT-proBNP and
      markers of fluid overload such as the ECW/body weight ratio (P < 0.0001) and the
      grade of peripheral oedema (P = 0.007), but not in patients without LVD.
      CONCLUSION: A serum NT-proBNP cut-off value of >/=7200 ng/L discriminates CKD
      stage 5 patients without LVD from those with LVD. In those patients with LVD,
      persistent post-dialytic volume overload correlates with elevated NT-proBNP
      levels.

PMID- 18089625
TI  - Changes in smoking among restaurant and bar employees following Norway's
      comprehensive smoking ban.
AB  - Norway implemented a nationwide ban on indoor smoking in June 2004. This study
      documents the smoking patterns of Norway's restaurant and bar workers before and
      after the ban, to determine changes in smoking prevalence and explore which
      individual and environmental characteristics were related to cessation. A
      national sample of food service workers was surveyed by telephone or Internet
      immediately before the ban and at 4 and 11 months post-implementation. Results
      showed that between baseline measurement and 4 months post-implementation, there
      were significant declines in prevalence of daily smoking (-3.6% points, p <
      0.005), daily smoking at work (-6.2% points, p < 0.001), number of cigarettes
      smoked by continuing smokers (-1.55, p < 0.001) and number of cigarettes smoked
      at work by continuing smokers (-1.63, p < 0.001). No significant changes occurred
      in any of these variables between 4 and 11 months post-implementation. Logistic
      regression analysis revealed that only smokers' intentions at baseline to quit
      within 30 days predicted cessation at both follow-up time points. In addition,
      cessation at 4 months was predicted by lower daily cigarette consumption at
      baseline, whereas cessation at 11 months was predicted by baseline attitude
      toward ETS and exposure to ETS as measured at follow-up. In sum, Norway's smoking
      ban was accompanied by a reduction in smoking in the period immediately following
      the ban, and the reduction was maintained almost a year later. The finding that
      smoking cessation was consistently associated with smokers' intentions to quit
      within 30 days suggests that motivational and support programs could play a
      significant role in boosting cessation rates. It is recommended that targeted
      interventions be used to supplement the benefits of a comprehensive ban to
      achieve tobacco control objectives.

PMID- 18089626
TI  - Significance levels for studies with correlated test statistics.
AB  - When testing large numbers of null hypotheses, one needs to assess the evidence
      against the global null hypothesis that none of the hypotheses is false. Such
      evidence typically is based on the test statistic of the largest magnitude, whose
      statistical significance is evaluated by permuting the sample units to simulate
      its null distribution. Efron (2007) has noted that correlation among the test
      statistics can induce substantial interstudy variation in the shapes of their
      histograms, which may cause misleading tail counts. Here, we show that
      permutation-based estimates of the overall significance level also can be
      misleading when the test statistics are correlated. We propose that such
      estimates be conditioned on a simple measure of the spread of the observed
      histogram, and we provide a method for obtaining conditional significance levels.
      We justify this conditioning using the conditionality principle described by Cox
      and Hinkley (1974). Application of the method to gene expression data illustrates
      the circumstances when conditional significance levels are needed.

PMID- 18089627
TI  - Low superior vena cava flow on day 1 and adverse outcome in the very low
      birthweight infant.
AB  - BACKGROUND: Superior vena cava (SVC) flow assesses blood flow from the upper
      body, and may provide a reliable assessment of systemic blood flow. AIM: (i) To
      assess the relationship between SVC flow in first 24 h and adverse outcome in
      very low birthweight (VLBW) infants (ii) To assess correlation between SVC flow
      and left and right ventricular outputs and anterior cerebral artery (ACA)
      velocity measurements. METHODS: A prospective, observational cohort study.
      Neonates with birthweight <1500 g were eligible and those with congenital heart
      disease (excluding patent ductus arteriosus) or major congenital malformations
      were excluded. Echocardiographic evaluation of SVC flow, right and left
      ventricular outputs and ductal patency was done in the first 24 h of life.
      Capillary refill time, blood pressure and urine output were also measured
      simultaneously. The primary outcome was intraventricular haemorrhage (IVH) grade
      > or = II and/or early neonatal death (<7 days). RESULTS: 40 VLBW neonates were
      enrolled following parental consent. Two were excluded. 8 babies (21%) had low
      flow states. There was no difference between the cohorts in median birth weight
      (1.14 kg vs 1.17 kg; p = 0.76), gestational age (26.5 vs 28.0 weeks,
      respectively; p = 0.12) or hours of life at examination (18.5 h vs 21 h,
      respectively; p = 0.36). The incidence of primary outcome (IVH > or = grade II
      and/or early neonatal death) was 50% and 6.7%, respectively (p = 0.01). There was
      no correlation between SVC flow and right ventricular outputs and ACA velocity
      and blood pressure measurements. CONCLUSIONS: 21% of our VLBW infants had low SVC
      flow in the first 24 h, and this was associated with early neonatal death and/or
      severe IVH.

PMID- 18089628
TI  - Noise levels during nCPAP are flow-dependent but not device-dependent.
AB  - OBJECTIVE: Nasal continuous positive airway pressure (nCPAP) has been shown to
      improve the outcome of infants with respiratory distress syndrome. However, noise
      generation could be of concern. Therefore, our study was designed to measure the
      noise levels of various CPAP drivers. DESIGN: For infants admitted to our
      neonatal intensive care unit and paediatric critical care unit, we measured the
      noise level in the oral cavity, using a microphonic probe with a flexible
      capillary tube. Various CPAP drivers and interfaces have been tested. RESULTS: 27
      measurements were made in eight infants. Mean noise level was 88.6 (SD 18.8) dB
      and was correlated with flow (p<0.01) but not with pressure. A noise level above
      90 dB was detected in 67% of the measurements. CONCLUSIONS: nCPAP drivers are
      valuable devices for neonatal care that may prevent primary mechanical
      ventilation or re-intubation, but generate a large amount of noise, often higher
      than occupational limits accepted for adult workers. Therefore, new devices must
      be designed to minimise this possible noxious exposure of premature infants to
      unacceptably high noise levels.

PMID- 18089629
TI  - Group B streptococcal disease in Portuguese infants younger than 90 days.
AB  - BACKGROUND: Group B streptococcus (GBS) is the most common isolate in mother
      related infection in newborns. AIMS: To evaluate the epidemiology of GBS
      infection in the first 90 days after birth; to determine if prophylaxis for early
      onset neonatal GBS infection can be based only on risk factors. DESIGN: National
      epidemiological surveillance. METHODS: Between April 2001 and March 2005 active,
      systematic, voluntary, national surveillance was performed through the Portuguese
      paediatric surveillance unit. CASE DEFINITION: any infant <90 days of age with
      GBS-positive culture in any normally sterile site-blood, cerebrospinal fluid
      (CSF), joint aspirate. Early-onset infection defined as in the first six full
      days after birth. RESULTS: 242 cases were reported (estimated cumulated incidence
      0.54/1000 live births (95% CI 0.47 to 0.61)). Infection occurred before day 7 in
      194 babies (81%); 13% presented between days 7 and 28; 6% between days 28-90. The
      incidence of early-onset infection was 0.44/1000 live births; 196 were term
      infants (81%), 160 of whom became ill before day 7; only 35 (22%) of these had
      one or more risk factors for infection. Overall, there were 229 positive blood
      cultures; 46 newborns had meningitis and 48 pneumonia. Mortality was 6.6%
      (16/242); it was similar for early (6.7%) and late-onset infection (6.3%), but
      varied by gestation-4.6% for term infants, 15.2% for preterm and 18% for babies
      born <1500 g. CONCLUSION: GBS infection is predominantly an early infection of
      the term infant. Mortality is higher in preterm and very low birthweight infants.
      GBS prophylaxis based on risk factors would leave untreated 78% of term babies
      who will present with early-onset disease.

PMID- 18089630
TI  - Morphine analgesia and gastrointestinal morbidity in preterm infants: secondary
      results from the NEOPAIN trial.
AB  - OBJECTIVE: To investigate the influence of morphine therapy and other factors on
      the attainment of full enteral feeds and on acquired gastrointestinal pathology
      in preterm infants. DESIGN: Secondary data analysis from a randomised, placebo
      controlled trial. SETTING: 16 neonatal intensive care units in USA, Sweden,
      France and UK. PATIENTS: 898 infants (treatment group 449, control 449).
      Gestation (median (range)): 27 (23-32) weeks; birth weight (median (range)): 985
      (420-2440) g. INTERVENTIONS: Morphine (M) or placebo (Pl) given pre-emptively by
      intravenous loading dose (100 microg/kg of morphine) and infusion (10-30
      microg/kg/h depending on gestation) while infants were ventilated, for up to 14
      days. "Open-label" morphine (A) could be given if clinically indicated. MAIN
      OUTCOME MEASURES: Age at full enteral feeds and major acquired gastrointestinal
      pathology. RESULTS: The group randomised to morphine was later in attaining full
      feeds (median days (quartiles): M 20 (13-29), Pl 17 (12-26); p = 0.003), and in
      starting feeds (median days (quartiles): M 5 (3-8), Pl 4 (2-7)). In a linear
      regression model, age at full feeds was independently associated with birth
      weight, a score of neonatal morbidities, neonatal dexamethasone use and
      cumulative morphine dose. There was no relationship between morphine use and
      acquired gastrointestinal pathology (M 9/449, Pl 8/449; chi2 p = 0.81).
      CONCLUSIONS: Morphine delays the attainment of full enteral feeds, partly by
      delaying the start of feeding, but does not discernibly increase gastrointestinal
      complications. The attainment of full feeds is influenced by morphine dose, but
      other factors seem to be important, including birth weight and neonatal
      morbidity.

PMID- 18089631
TI  - Exposure to environmental tobacco smoke and sensitisation in children.
AB  - BACKGROUND: Exposure to environmental tobacco smoke (ETS) increases the risk of
      respiratory illness in children but data are inconclusive regarding the risk of
      IgE sensitisation. OBJECTIVE: To elucidate whether exposure to smoking prenatally
      and/or postnatally is related to IgE sensitisation in children at 4 years of age.
      METHODS: As part of a prospective birth cohort study (BAMSE), a total of 4089
      families with children answered questionnaires when the child was 2 months, 1, 2
      and 4 years old on environmental factors and symptoms of allergic disease. Blood
      collected at age 4 years from 2614 children was analysed for IgE antibodies to
      common inhalant and food allergens. Odds ratios (OR) and 95% confidence intervals
      (CI) were calculated using logistic regression with adjustments for potential
      confounders. RESULTS: There was no evident association between maternal smoking
      during pregnancy and risk of IgE sensitisation. In contrast, a dose-response
      effect was found for exposure to ETS from parental smoking during the first few
      months of life and IgE sensitisation. There was an increased risk of
      sensitisation to inhalant and/or food allergens (OR(adj) 1.28 (95% CI 1.01 to
      1.62)) among children exposed to ETS at 2 months of age. The risk appeared
      particularly elevated for indoor inhalant allergens, such as cat (OR(adj) 1.96
      (95% CI 1.28 to 2.99)) and for food allergens (OR(adj) 1.46 (95% CI 1.11 to
      1.93)). The IgE sensitising effect of ETS seemed to be confined to infants of
      parents without allergic diseases and to ETS exposure during early infancy.
      CONCLUSIONS: Our data indicate that exposure in early infancy to ETS increases
      the risk of IgE sensitisation to indoor inhalant and food allergens.

PMID- 18089632
TI  - Prader-Willi syndrome: who can have growth hormone?
AB  - Growth hormone (GH) is licensed for treatment for Prader-Willi syndrome (PWS) for
      improvement of body composition,1(-)3 height velocity, mobility, behaviour and
      quality of life.4 Recent case reports, however, have pointed out the occurrence
      of sudden death during initiation of GH, mainly during sleep and possibly related
      to severe obesity and sleep-disordered breathing (SDB).5(-)15 Concerns for an
      increased mortality in PWS children starting GH therapy led to a call for
      cessation of its use. Children with PWS are at risk of developing SDB secondary
      to both deficient autonomic sleep control and upper airway obstruction (UAO). It
      has been suggested that GH exacerbates pre-existing gas-exchange deficiencies in
      three ways: (a) by stimulation of adenotonsillar hypertrophy;16 17 (b) by a rise
      in basal metabolic rate with a resultant rise in oxygen demand;18 and (c) by
      normalisation of previously decreased hydration with augmentation of volume
      load.19 Are we withholding GH therapy, a treatment known to be of benefit in PWS,
      without adequate evidence to justify our actions? We consider it safe to treat
      severely obese children with GH once SDB is addressed using respiratory support
      such as continuous positive airway pressure (CPAP) or bilevel positive airway
      pressure (BiPAP). In this paper, we evaluate the current evidence for the use of
      GH in PWS from a respiratory bias and propose a pathway for the identification
      and monitoring of these "at risk" patients.

PMID- 18089633
TI  - Regional differences in overweight: an effect of people or place?
AB  - OBJECTIVE: To examine UK country and English regional differences in childhood
      overweight (including obesity) at 3 years and determine whether any differences
      persist after adjustment for individual risk factors. DESIGN: Nationally
      representative prospective study. SETTING: England, Wales, Scotland and Northern
      Ireland. PARTICIPANTS: 13 194 singleton children from the UK Millennium Cohort
      Study with height and weight data at age 3 years. MAIN OUTCOME MEASURE:
      Overweight (including obesity) was defined according to the International Obesity
      TaskForce cut-offs for body mass index, which are age and sex specific. RESULTS:
      At 3 years of age, 23% (3102) of children were overweight or obese. In
      univariable analyses, children from Northern Ireland (odds ratio 1.30, 95%
      confidence interval 1.14 to 1.48) and Wales (1.26, 1.11 to 1.44) were more likely
      to be overweight than children from England. There were no differences in
      overweight between children from Scotland and England. Within England, children
      from the East (0.71, 0.57 to 0.88) and South East regions (0.82, 0.68 to 0.99)
      were less likely to be overweight than children from London. There were no
      differences in overweight between children from other English regions and
      children from London. These differences were maintained after adjustment for
      individual socio-demographic characteristics and other risk factors for
      overweight. CONCLUSIONS: UK country and English regional differences in early
      childhood overweight are independent of individual risk factors. This suggests a
      role for policies to support environmental changes that remove barriers to
      physical activity or healthy eating in young children.

PMID- 18089634
TI  - Two doses of pamidronate in infants with osteogenesis imperfecta.
AB  - INTRODUCTION: Current regimens of intravenous pamidronate for infants and
      children with osteogenesis imperfecta (OI) typically deliver 3-12 mg/kg/year of
      drug. We wished to ascertain the effect of pamidronate at 6 or 12 mg/kg/year on
      skeletal health in infants with OI. METHODS: We recruited 12 infants over a
      period of 4 years. Infants received either 6 or 12 mg/kg/year of pamidronate.
      Bone outcomes were assessed by skeletal surveys and DXA bone density measurements
      at baseline and at 12 months. RESULTS: Bone mass increased in both groups.
      Infants receiving 12 as opposed to 6 mg/kg/year pamidronate had increased spine
      bone density after adjusting for covariates at study entry (p = 0.04). Crush
      fractures improved or remained unchanged in all but one infant. Biochemical
      markers of bone turnover fell but remained within or above the normal range for
      age. Metaphyseal remodelling was not impaired. CONCLUSIONS: Pamidronate dose in
      infants may influence lumbar spine bone acquisition. Pamidronate improved
      vertebral size after prior crush fracturing and did not over-suppress bone
      turnover.

PMID- 18089635
TI  - Children's consent and paediatric research: is it appropriate for healthy
      children to be the decision-makers in clinical research?
AB  - AIM: To determine the appropriateness of asking healthy children to make a
      decision regarding participation in a research study. METHODS: Participants
      constituted a group of children taking part in a follow-up to a vaccine study
      which involved a blood test to look at the persistence of antibodies. Information
      about the study was given to each child and following venepuncture an oral
      questionnaire was completed to establish understanding of the vaccine study.
      Parental views concerning their child's ability to make a decision regarding
      research participation were also sought. RESULTS: 73 children participated
      overall. Following venepuncture 59% (n = 43) had grasped some aspect of the
      reasoning behind venepuncture with 33% (n = 24) unclear. The majority of parents
      (n = 55) and a substantial number of children (n = 28) believed that the parent
      should make the decision about study participation, although it is clear that a
      significant minority of parents thought it is right to involve the child in that
      process. CONCLUSION: New guidance about the requirements for informed consent
      involving children in research is needed, which can respect the autonomy of the
      child and the role of the parent, while recognising the limited capacity of some
      children to understand age-appropriate information.

PMID- 18089636
TI  - Rac1 mediates the osteoclast gains-in-function induced by haploinsufficiency of
      Nf1.
AB  - Neurofibromatosis type I (NF1) is a congenital disorder resulting from loss-of
      function of the tumor suppressor gene, NF1, a GTPase-activating protein for
      p21ras. Fifty percent of NF1 patients have osseous manifestations including a
      high incidence of osteoporosis. Osteoclasts are specialized macrophage/monocyte
      lineage-derived cells that resorb bone and NF1 haploinsufficient osteoclasts have
      abnormal Ras-dependent bone resorption. Ras-regulated functions are in part
      mediated via the activation of small Rho family of GTPases including the Rac
      GTPases. In the present study, we demonstrate that the Rho-GTPase Rac1 is a
      crucial Ras-mediated effector in Nf1 haploinsufficient (+/-) osteoclasts. Nf1+/-
      mice were intercrossed with conditional Rac1(flox/flox)Mxcre+ (Rac1-/-) mice to
      generate Nf1+/-; Rac1-/- mice. Genetic disruption of Rac1 restored the
      pathological increase in osteoclast progenitor cells in Nf1+/- mice and was
      sufficient to correct the increased Nf1+/- osteoclast motility and osteoclast
      belt formation, an f-actin structure observed in mature osteoclasts critical for
      bone resorption and lytic activity. Finally, we demonstrate that Nf1+/-; Rac1-/-
      osteoclasts have normalized Erk activation compared with Nf1+/- osteoclasts, a
      biochemical function critical for osteoclast formation, actin organization and
      motility. Collectively, these data demonstrate that Rac1 critically contributes
      to increased osteoclast function induced by haploinsufficiency of Nf1 and
      implicate Rac1 as a rational therapeutic target for osteoporosis.

PMID- 18089637
TI  - Orthostatic panic attacks among Vietnamese refugees.
AB  - Viewed historically and cross-culturally, orthostatic-induced dizziness, i.e.,
      dizziness caused by standing up from a sitting or a lying position, forms a key
      aspect of many syndromes: irritable heart (American Civil War), effort syndrome
      (World War I and World War II), chronic fatigue syndrome (contemporary USA), Gulf
      War syndrome (contemporary USA), and orthostatic dysregulation (contemporary
      Japan). Among Vietnamese refugees attending a psychiatric clinic, this study
      documents a high rate of orthostatic panic (OP), as well as certain processes
      seemingly generating these panic attacks, viz., flashbacks and culturally
      specific catastrophic cognitions. Case examples are used to demonstrate OP's
      phenomenology and relevance to clinical care. To illustrate the mechanisms
      producing OP, we adduce the multiplex model of panic generation. Culturally
      appropriate care of Vietnamese refugees should include assessment and treatment
      of OP.

PMID- 18089638
TI  - Coping with loss and bereavement in post-war Tigray, Ethiopia.
AB  - Drawing upon data collected through in-depth interviews with 20 victims of the
      Ethio-Eritrean war, this article addresses how psychosocial impacts of political
      violence are coped with in a Tigrayan context in northern Ethiopia. Qualitative
      procedures of condensation and categorization of interview texts revealed that
      informants presented three kinds of coping strategies, all aimed at avoiding
      indulging in sorrow: (1) diverted thinking, (2) distraction, and (3) future
      investment. As their main rationale for employing such coping strategies,
      informants reported the belief that grieving and crying would have negative
      impacts on their health, their household, and on their relationship with God.
      This belief is discussed in terms of how it is informed by sociocultural
      discourses of the Tigrayan community in general, and discourses of the Ethiopian
      Orthodox Church in particular. Some implications concerning the mismatch between
      the western trauma discourse and local discourses for psychosocial coping are
      discussed.

PMID- 18089639
TI  - Impact of September 11 on refugees and those seeking asylum.
AB  - September 11, 2001 profoundly affected the American public. We share the views of
      a cohort of refugees and those seeking asylum from the Boston Center for Refugee
      Health and Human Rights. Of the 63 individuals from 18 countries interviewed,
      many had concerns about their personal safety following September 11, as well as
      fears related to deportation, arrest, detention, imprisonment, discrimination,
      physical violence and the destruction of property, and war. Asylum seekers were
      more likely than refugees to have concerns about their safety before their
      departure and during flight, as well as fear deportation and arrest after
      September 11. In the wake of September 11, most common coping strategies utilized
      included prayer (77.8%), speaking with friends from their own social group
      (47.6%), family (44.4%), and belief in fate (42.9%).

PMID- 18089640
TI  - When the poetry no longer rhymes: mental health issues among Somali immigrants in
      the USA.
AB  - To identify and explore cultural dynamics influencing the psychiatric care of
      immigrant Somalis in the USA, we reviewed demographic data from Minnesota
      Departments of Human Services, and interviewed health professionals, exploring
      community perceptions of medical/psychiatric needs, cultural characteristics,
      barriers to care, and potential solutions. An informal survey of 37 members of
      the Mayo Clinic Department of Psychiatry and Psychology, to determine caregiver
      perceptions of care of Somali patients, cited language barriers (74%), and
      cultural misperceptions (68%) as the most frequent obstacles. Difficulties
      working within the patriarchal family structure, limited community resources,
      poor compliance, and financial issues ranged between 18 and 8%. Additional
      barriers mentioned were problems working with interpreters from ;warring clan
      factions,' patients' fears of being labeled ;crazy,' difficulties viewing illness
      within an emotional framework, and the need to address mental health from a
      physical framework through a focus on somatic symptoms. Somalis rarely
      acknowledge psychiatric problems and common traditional treatments have become
      ineffective in the new context. Recommendations include alternative health care
      approaches utilizing family values, ;bargaining,' and educational approaches to
      acculturation.

PMID- 18089641
TI  - The mental health of asylum-seeking and refugee children and adolescents
      attending a clinic in the Netherlands.
AB  - We investigated the sociodemographic and clinical characteristics of asylum
      seeking and refugee children and adolescents referred to a child and adolescent
      psychiatry service in the Netherlands. Children with families and unaccompanied
      minors were compared. Unaccompanied minors had significantly higher frequencies
      of symptoms and psychiatric disorders than the children with families, both
      considered a high-risk population for mental health problems.

PMID- 18089642
TI  - Mental distress and the coping strategies of elderly Indian immigrant women.
AB  - This article explores how elderly English-speaking Indian immigrant women living
      in Edmonton, Alberta, Canada perceive and manage mental distress. With elders'
      consent, in-depth interviews were recorded, transcribed and transcripts were
      thematically analyzed. The findings suggest that these women believed that to
      lower the risk of mental distress it is critical for individuals to ;maximize
      control over inner self' by ;being busy.' The elder's busy behavior is framed
      within the Indian cultural and spiritual/faith matrix in dialogue with
      acculturation experiences in Canada. ;Staying busy' allows these elders to use
      culture as a ;moral medicine' to facilitate coping and adaptation.

PMID- 18089643
TI  - Views on depression among patients diagnosed as depressed in a poor town on the
      outskirts of Sao Paulo, Brazil.
AB  - Depression has important cultural and social components. Interviews with 16 women
      living in the poor and violent outskirts of Sao Paulo were analyzed to identify
      local concepts of depression. The interviews were conducted with women who were
      diagnosed with depression and patients in treatment at a primary care unit. For
      these women, depression was inextricably woven into their violent and downtrodden
      daily lives, as well as with other sources of suffering. The local community
      identified two types of depression: 'true' and 'false,' suggesting a concept
      enmeshed with morality.

PMID- 18089644
TI  - Open papers, open minds? Media representations of psychiatric de
      institutionalization in Jamaica.
AB  - Little research has been conducted on media representations of psychiatric de
      institutionalization in low-income countries. We set out to examine whether the
      Jamaican media takes a positive or negative orientation to psychiatric de
      institutionalization, and which arguments and rhetorical devices are employed to
      support the media's position. This was done by the collection, review, and
      analysis of all stories related to psychiatric de-institutionalization published
      over a 26-month period from 2003 to 2005 by Jamaica's principal broadsheet
      newspaper. All of the stories were positive in orientation. Articles alluded to
      the therapeutic and economic benefits of de-institutionalization. To allay public
      fears, articles gave prominence to the views of senior psychiatric experts,
      quoted supporting statistics and international trends, and translated relevant
      research findings into lay language. Our results are contrary to most studies in
      high-income countries indicating negative media portrayals of mental illness and
      the mentally ill.

PMID- 18089645
TI  - Translation, validation and cultural aspects of postpartum depression screening
      scale in Brazilian Portuguese.
AB  - The aim of this study was to determine the validity and reliability of a
      Portuguese version of the Postpartum Depression Screening Scale (PDSS). A total
      of 120 new mothers completed the translated version of PDSS and later were
      interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders,
      our gold standard for clinical status. The best cut-off score for the Portuguese
      version was 102, with a sensibility of 94%, a specificity of 95%, a positive
      predictive value of 75% and a negative predictive value of 99%. Reliability,
      measured by the alpha coefficient of internal consistency, was .95. The PDSS is
      considered ready for use in the screening of Brazilian new mothers for postpartum
      depression.

PMID- 18089646
TI  - Molecular markers and changes of computed tomography appearance in lung
      adenocarcinoma with ground-glass opacity.
AB  - BACKGROUND: High-resolution computed tomography (HRCT) of lung adenocarcinoma at
      early stage shows pure ground-glass opacity (GGO) and most cases of pure GGO
      remain stable during follow-up. There is no consensus on the strategy for follow
      up. Identification of the molecular mechanisms that are associated with the
      natural history of lung adenocarcinoma should provide useful information.
      METHODS: Twenty-three lung adenocarcinomas that were followed-up for more than 6
      months pre-operatively by HRCT were included in this study. Patterns of
      radiological changes during the follow-up period were classified into three
      groups; type 1, pure GGO without consolidation; type 2, appearance or increase in
      consolidation within pure GGO; type 3, consolidation without pure GGO. Mutational
      analysis of the epidermal growth factor receptor (EGFR) and K-ras genes and
      immunohistochemical staining of p53 protein were performed. RESULTS: EGFR
      mutations were found in 17 cases (74%), and there was no K-ras mutation. Positive
      staining of p53 was found in 8 cases (35%). As for radiological findings during
      the follow-up period, the frequencies of EGFR mutations and positive p53 staining
      were 67 and 0% in type 1 (n = 9), 89 and 44% in type 2 (n = 9) and 60 and 80% in
      type 3 (n = 5). CONCLUSIONS: EGFR mutations were frequently found in lung
      adenocarcinoma with GGO on HRCT in this study. Inactivation of p53 may be
      associated with the appearance of central consolidation within pure GGO on HRCT
      which reflects invasive features and may be useful as a molecular marker during
      the follow-up of pure GGO.

PMID- 18089647
TI  - Endothelin-1 enhances nuclear Ca2+ transients in atrial myocytes through
      Ins(1,4,5)P3-dependent Ca2+ release from perinuclear Ca2+ stores.
AB  - Nuclear Ca2+ plays a key role in the regulation of gene expression. Inositol
      (1,4,5)-trisphosphate [Ins(1,4,5)P3)] might be an important regulator of nuclear
      Ca2+ but its contribution to nuclear Ca2+ signalling in adult cardiomyocytes
      remains elusive. We tested the hypothesis that endothelin-1 enhances nuclear Ca2+
      concentration transients (CaTs) in rabbit atrial myocytes through Ins(1,4,5)P3
      induced Ca(2+) release from perinuclear stores. Cytoplasmic and nuclear CaTs were
      measured simultaneously in electrically stimulated atrial myocytes using confocal
      Ca2+ imaging. Nuclear CaTs were significantly slower than cytoplasmic CaTs,
      indicative of compartmentalisation of intracellular Ca2+ signalling. Endothelin-1
      elicited a preferential (10 nM) or a selective (0.1 nM) increase in nuclear
      versus cytoplasmic CaTs. This effect was abolished by inhibition of endothelin-1
      receptors, phospholipase C and Ins(1,4,5)P3 receptors. Fractional Ca2+ release
      from the sarcoplasmic reticulum and perinuclear stores was increased by
      endothelin-1 at an otherwise unaltered Ca2+ load. Comparable increases of
      cytoplasmic CaTs induced by beta-adrenoceptor stimulation or elevation of
      extracellular Ca2+ could not mimic the endothelin-1 effects on nuclear CaTs,
      suggesting that endothelin-1 specifically modulates nuclear Ca2+ signalling.
      Thus, endothelin-1 enhances nuclear CaTs in atrial myocytes by increasing
      fractional Ca2+ release from perinuclear stores. This effect is mediated by the
      coupling of endothelin receptor A to PLC-Ins(1,4,5)P3 signalling and might
      contribute to excitation-transcription coupling.

PMID- 18089648
TI  - Cdc42 and the Ste20-like kinase Don3 act independently in triggering cytokinesis
      in Ustilago maydis.
AB  - In the dimorphic fungus Ustilago maydis the Rho-family GTP-binding protein Cdc42
      and the Ste20-like kinase Don3 are both essential for triggering cell separation
      during cytokinesis. Since Don3 does not contain a Cdc42/Rac interaction and
      binding domain (CRIB), it is unclear how Cdc42 and Don3 cooperate in the
      regulation of cytokinesis. To analyse the regulatory network we generated an
      analogue-sensitive Don3 variant (Don3-as) that allows specific inhibition in
      vivo. The engineered kinase Don3(M157A) is fully active in vivo and can be
      specifically inhibited by low concentrations of the ATP-analogue NA-PP1.
      Inhibition of the Don3-as kinase activity immediately blocked cell separation
      resulting in the formation of clusters of nonseparated cells. Covalent labelling
      of cell wall proteins showed that, upon release of inhibition, cytokinesis was
      resumed instantaneously in all cells. By sequentially activating Don3 and Cdc42
      we were able to demonstrate that both proteins act independently of each other
      and that Don3 activity precedes that of Cdc42. We provide evidence that Don3 and
      Cdc42 are crucial for the assembly of a contractile actomyosin ring, which is a
      prerequisite for secondary septum formation. We propose, that Don3 is involved in
      establishing a landmark, at which the Cdc42-dependent actomyosin ring formation
      will occur.

PMID- 18089649
TI  - Neurofibromin as a regulator of melanocyte development and differentiation.
AB  - Patients with the genetic disease type I neurofibromatosis (NF1) exhibit
      characteristic pigmentary lesions associated with loss of a single allele of NF1,
      encoding the 260 kDa protein neurofibromin. To understand the basis for these
      pigmentary problems, the properties of melanocytes haploinsufficient for the
      murine gene Nf1 were studied using Nf1(+/-) knockout mice. We demonstrate that
      neurofibromin regulates the Kit-Mitf signaling axis in vivo during melanocyte
      development. Primary Nf1(+/-) melanocytes were purified by FACS to measure
      melanogenic gene expression. We found that Nf1(+/-) melanocytes exhibit higher
      levels of melanogenic gene expression than their wild-type counterparts. Both
      prior to and following Kit stimulation, Nf1(+/-) melanocytes also exhibit
      increased activation of the MAP kinase pathway compared with primary cells. The
      melanogenic response of primary melanocytes to Mek inhibition is consistent with
      the changes observed with Nf1 haploinsufficiency; however, these changes differ
      from those observed with their immortalized counterparts. The observation that
      reduction of neurofibromin, either from haploinsufficiency in the case of primary
      melanocytes or from neurofibromin knockdown in the case of melan-a cells,
      enhances melanogenic gene expression suggests that neurofibromin plays a dominant
      role to MEK activity in controlling melanogenic gene expression in murine
      melanocytes.

PMID- 18089650
TI  - A homologous recombination defect affects replication-fork progression in
      mammalian cells.
AB  - Faithful genome transmission requires a network of pathways coordinating DNA
      replication to DNA repair and recombination. Here, we used molecular combing to
      measure the impact of homologous recombination (HR) on the velocity of DNA
      replication forks. We used three hamster cell lines defective in HR either by
      overexpression of a RAD51 dominant-negative form, or by a defect in the RAD51
      paralogue XRCC2 or the breast tumor suppressor BRCA2. Irrespectively of the type
      or extent of HR alteration, all three cell lines exhibited a similar reduction in
      the rate of replication-fork progression, associated with an increase in the
      density of replication forks. Importantly, this phenotype was completely reversed
      in complemented derivatives of Xrcc2 and Brca2 mutants. These data reveal a novel
      role for HR, different from the reactivation of stalled replication forks, which
      may play an important role in genome stability and thus in tumor protection.

PMID- 18089651
TI  - Concerning the origin of malignant tumours by Theodor Boveri. Translated and
      annotated by Henry Harris. Preface.

PMID- 18089652
TI  - Concerning the origin of malignant tumours by Theodor Boveri. Translated and
      annotated by Henry Harris.

PMID- 18089653
TI  - Two-dimensional gas chromatography/electron-impact mass spectrometry with
      cryofocusing for simultaneous quantification of MDMA, MDA, HMMA, HMA, and MDEA in
      human plasma.
AB  - BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA, or Ecstasy) is a popular
      recreational drug. Analysis of MDMA and metabolites in human plasma, particularly
      in pharmacokinetic studies, requires low limits of quantification. Two
      dimensional GC/MS with cryofocusing is a chromatographic technique recognized for
      its increased selectivity and resolution. METHODS: This method simultaneously
      quantifies 3,4-methylenedioxyethylamphetamine (MDEA), MDMA, and its metabolites,
      3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA),
      and 4-hydroxy-3-methoxyamphetamine (HMA) in human plasma. With hydrochloric acid,
      we hydrolyzed 1 mL plasma, fortified with internal standard. Analytes were
      subjected to solid-phase extraction, derivatized with heptafluorobutyric acid
      anhydride, and quantified using cryofocused 2-dimensional GC/MS operated in
      electron-impact selected ion-monitoring mode. RESULTS: Limits of quantification
      were 1.0 microg/L for MDA and 2.5 microg/L for MDEA, MDMA, HMMA, and HMA.
      Calibration curves were linear to 100 microg/L for MDA and HMA and to 400
      microg/L for MDEA, MDMA, and HMMA, with r(2) > 0.997. At 3 concentrations
      spanning the linear dynamic range of the assay, mean overall extraction
      efficiencies from plasma were > or =85% for all compounds of interest. Recoveries
      were 85.6% to 107.2% of target, and intra- and interassay imprecision (CV) was
      <8.5% for all drugs at 3 concentrations within the range of the assay. None of
      the 66 exogenous compounds tested interfered with analyte quantification.
      CONCLUSIONS: This GC/MS assay provides low limits of quantification for
      simultaneous determination of MDEA, MDMA, and metabolites MDA, HMMA, and HMA in
      human plasma. The 2D chromatographic system should be suitable for application to
      other analytes and to other complex matrices.

PMID- 18089654
TI  - DNA methylation biomarkers for blood-based colorectal cancer screening.
AB  - BACKGROUND: Sensitive, specific blood-based tests are difficult to develop unless
      steps are taken to maximize performance characteristics at every stage of marker
      discovery and development. We describe a sieving strategy for identifying high
      performing marker assays that detect colorectal cancer (CRC)-specific methylated
      DNA in plasma. METHODS: We first used restriction enzyme-based discovery methods
      to identify marker candidates with obviously different methylation patterns in
      CRC tissue and nonpathologic tissue. We then used a selection process
      incorporating microarrays and/or real-time PCR analysis of tissue samples to
      further test marker candidates for maximum methylation in CRC tissue and minimum
      amplification in tissues from both healthy individuals and patients with other
      diseases. Real-time assays of 3 selected markers were validated with plasma
      samples from 133 CRC patients and 179 healthy control individuals in the same age
      range. RESULTS: Restriction enzyme-based testing identified 56 candidate markers.
      This group was reduced to 6 with microarray and real-time PCR testing. Three
      markers, TMEFF2, NGFR, and SEPT9, were tested with plasma samples. TMEFF2
      methylation was detected in 65% [95% confidence interval, 56%-73%] of plasma
      samples from CRC patients and not detected in 69% (62%-76%) of the controls. The
      corresponding results for NGFR were 51% (42%-60%) and 84% (77%-89%); for SEPT9,
      the values were 69% (60%-77%) and 86% (80%-91%). CONCLUSIONS: The stringent
      criteria applied at all steps of the selection and validation process enabled
      successful identification and ranking of blood-based marker candidates.

PMID- 18089655
TI  - Plasma uric acid and the risk of type 2 diabetes in a Chinese community.
AB  - BACKGROUND: Previous cross-sectional studies have shown hyperuricemia to be
      prevalent among individuals with metabolic syndrome, but the evidence from
      prospective studies of an association between uric acid and diabetes risk is
      limited. We prospectively investigated the association between plasma
      concentrations of uric acid and the incidence of type 2 diabetes in Chinese
      individuals. METHODS: We conducted a community-based prospective cohort study of
      2690 participants (age range, 35-97 years) in the Chin-Shan Community
      Cardiovascular Cohort Study, who were found to be free of diabetes and
      cardiovascular disease during baseline assessment at study entry in 1990. During
      a median 9.0-year follow-up, 548 participants developed type 2 diabetes. RESULTS:
      High plasma uric acid concentrations were associated with a higher prevalence of
      metabolic syndrome. After adjustment for age, sex, body mass index, and other
      covariates, the relative risks (RR) of diabetes according to uric acid quintile
      were 1.11, 1.29, 1.40, and 1.63 [95% confidence interval (CI), 1.20-2.23; P for
      trend <0.001]. After additional adjustment for metabolic syndrome, the RR for
      comparing the participants in the fifth and first uric acid quintiles was 1.40
      (95% CI, 1.02-1.92; P for trend = 0.027). In joint analyses, participants who
      were in the highest uric acid quintile and also had metabolic syndrome had a 3.3
      fold greater risk of diabetes (95% CI, 2.27-4.94) than those in the lowest uric
      acid quintile and without metabolic syndrome. CONCLUSIONS: These findings suggest
      a modest positive association between plasma uric acid concentration and the
      incidence of type 2 diabetes in Chinese individuals. The association between
      hyperuricemia and diabetes was partly mediated through the metabolic syndrome.

PMID- 18089656
TI  - Prevalence and cluster of cardiometabolic biomarkers in overweight and obese
      schoolchildren: results from a large survey in southwest Germany.
AB  - BACKGROUND: Obesity is associated with substantial metabolic changes and
      subclinical inflammation. We explored associations between body mass index (BMI)
      and cardiometabolic biomarkers and their clustering in overweight and obese
      schoolchildren. METHODS: In this population-based, cross-sectional study among
      450 children 10 years old, we measured adiponectin, leptin, inflammatory markers,
      apolipoprotein (apo) AI and B, and lipoprotein-associated phospholipase A(2) (Lp
      PLA(2)). Except for adiponectin and apoAI (10th percentile) the 90th percentile
      was used as cutoff point. Body weight was categorized in age- and sex-specific
      BMI percentiles and overweight and obesity according to International Obesity
      Task Force definitions. RESULTS: In linear regression models, all cardiometabolic
      markers except apoB were statistically significantly associated with overweight.
      In logistic regression models, compared with the reference category (25th-75th
      percentile of BMI), overweight was associated with increased concentrations of
      leptin [odds ratio (OR) 59.80; 95% CI 16.68-214.39], C-reactive protein (6.30;
      2.95-13.45), fibrinogen (2.82; 1.33-6.01), and low apoAI (2.62; 1.19-5.75).
      Overweight was positively associated with interleukin-6, Lp-PLA(2), and apoB
      concentrations and inversely with adiponectin concentrations. Most importantly,
      in obese children 35% showed one, 20% two, 10% three, and 15% four or more
      abnormal cardiometabolic biomarkers. The number of abnormal cardiometabolic
      markers increased in overweight (p(trend) <0.001) and obese (p(trend) <0.001)
      children. CONCLUSIONS: Overweight and obesity in children are associated with
      complex metabolic changes and a low-grade inflammatory response, and thus might
      not only accelerate cardiovascular disease later on, but may also be associated
      with the initiation of atherosclerosis in early life.

PMID- 18089657
TI  - Influence of pancreatic status and sex on polyunsaturated fatty acid profiles in
      cystic fibrosis.
AB  - BACKGROUND: Some but not all studies have reported abnormal polyunsaturated fatty
      acid composition in cystic fibrosis (CF) patients. We investigated the influence
      of pancreatic status and sex on the fatty acid profile in plasma and erythrocyte
      membranes in patients with CF. METHODS: After a 1-step transesterification with
      acetyl chloride on plasma and washed erythrocyte membranes, we quantified fatty
      acid methyl esters by use of GC-MS in 124 CF patients and 80 age-matched healthy
      controls. In the CF group, mean (SD) age was 17.5 (11.3) years, and 51.6% were
      male. Pancreatic insufficiency was diagnosed in 78% of the CF population.
      RESULTS: A decrease in docosahexaenoic acid concentrations was observed in CF
      patients independently of pancreatic status. Pancreatic insufficient CF patients
      displayed lower concentrations of linoleic acid and arachidonic acid and higher
      concentrations of dihomo-gamma-linolenic acid and eicosatrienoic acid (mead acid)
      in plasma and erythrocyte membranes compared with healthy controls and pancreatic
      sufficient CF patients. Male CF patients had significantly lower docosahexaenoic
      acid and higher eicosatrienoic acid in plasma and erythrocyte membranes compared
      with female CF patients. CONCLUSIONS: These results support the concept that
      multiple abnormalities of polyunsaturated fatty acid composition participate in
      the CF disease phenotype and that pancreatic status plays a major role in such
      abnormalities. Moreover, patient sex influences the polyunsaturated fatty acid
      spectrum in CF, with more marked abnormalities in males.

PMID- 18089658
TI  - Characterization of globin RNA interference in gene expression profiling of whole
      blood samples.
AB  - BACKGROUND: Blood-based biomarker discovery with gene expression profiling has
      been hampered by interference from endogenous, highly abundant alpha- and beta
      globin transcripts. We describe a means to quantify the interference of globin
      transcripts on profiling and the effectiveness of globin transcript mitigation by
      (a) defining and characterizing globin interference, (b) reproducing globin
      interference with synthetic transcripts, and (c) using ROC curves to measure
      sensitivity and specificity for a protocol for removing alpha- and beta-globin
      transcripts. METHODS: We collected blood at 2 sites and extracted total RNA in
      PreAnalytiX PAXgene tubes. As a reference for characterizing interference, we
      supplemented aliquots of total RNA with synthesized globin transcripts and total
      RNA from human brain. Selected aliquots were processed with Ambion GLOBINclear to
      remove globin transcripts. All aliquots were labeled and hybridized to Agilent
      DNA microarrays by means of pooling schemes designed to quantify the mitigation
      of globin interference and to titrate gene expression signatures. Quantitative
      reverse transcription-PCR data were generated for comparison with microarray
      results. RESULTS: Our supplementation and pooling strategy for comparing the
      microarray data among samples demonstrated that mitigation could reduce an
      interference signature of >1000 genes to approximately 200. Analysis of samples
      of endogenous globin transcripts supplemented with brain RNA indicated that
      results obtained with the GLOBINclear treatment approach those of peripheral
      blood mononuclear cell preparations. CONCLUSION: We confirmed that both the
      absolute concentrations of globin transcripts and differences in transcript
      concentrations within a sample set are factors that cause globin interference
      (Genes Immun 2005;6:588-95). The methods and transcripts we have developed may be
      useful for quantitatively characterizing globin mRNA interference and its
      mitigation.

PMID- 18089659
TI  - Sources of variation of commonly measured serum analytes in 6 Asian cities and
      consideration of common reference intervals.
AB  - BACKGROUND: In a previous study to determine the feasibility of common reference
      intervals in Asia, we found significant differences among populations from 6
      cities. In this study, we attempted to define the sources of these differences.
      METHODS: We enrolled 580 healthy volunteers (279 men, 301 women, 20-62 years
      old), after a selection process that was based on the Clinical and Laboratory
      Standards Institute guidelines, and used a lifestyle questionnaire. All sera were
      obtained at a basal state and frozen at -80 degrees C until the collective assay
      was done. We measured 21 basic chemical analytes and 10 serum proteins. RESULTS:
      We used 3-level nested ANOVA to separate the variation (SD) into between-city (SD
      city), between-sex (SD-sex), between-age (SD-age), and between-individual (SD
      indiv) components. SD-indiv corresponds to one-quarter of the "pure" reference
      interval obtained after removing variations due to city, sex, and age. The SD-sex
      to SD-indiv ratio was >0.8 for creatinine, urate, retinol-binding protein, and
      transthyretin. We observed high SD-city to SD-indiv ratios, ranging from 0.4 to
      0.7, for 11 analytes including lactate dehydrogenase (LDH), electrolytes, IgG,
      and complement components and SD-age to SD-indiv ratios >0.4 for LDH, alkaline
      phosphatase, and total cholesterol. Multiple regression analysis demonstrated
      several other relevant sources of variation, including body mass index, alcohol
      consumption, and cigarette smoking, although their contributions were generally
      smaller than those for sex, region, or age. CONCLUSION: We observed unacceptably
      large regional differences in measured values of some analytes even after
      adjustment for age, sex, and lifestyle variables. Genetic and environmental
      factors may account for the residual differences.

PMID- 18089660
TI  - Lipoprotein(a) and cardiovascular disease in ethnic Chinese: the Chin-Shan
      Community Cardiovascular Cohort Study.
AB  - BACKGROUND: Little is known about lipoprotein(a) [Lp(a)] as a predictor of
      vascular events among ethnic Chinese. We prospectively investigated the
      association of Lp(a) with cardiovascular disease and all-cause death in a
      community-based cohort. METHODS: We conducted a community-based prospective
      cohort study of 3484 participants (53% women; age range, 35-97 years) who had
      complete lipid measurements and were free of a cardiovascular disease history at
      the time of recruitment. Over a median follow-up of 13.8-years, we documented 210
      cases of stroke, 122 cases of coronary heart disease (CHD), and 781 deaths.
      RESULTS: The incidences for each event increased appreciably with Lp(a) quartile
      for stroke and all-cause death, but not for CHD. Baseline Lp(a) concentration by
      quartile was not significantly associated with stroke, all-cause death, and CHD
      in multivariate analyses. The multivariate relative risk was significant for
      stroke at the 90th and 95th percentiles and for total death at the 95th and 99th
      percentiles. CONCLUSIONS: Our findings suggest a threshold relationship with
      little gradient of risk across lower Lp(a) values for stroke and all-cause death
      in Chinese adults.

PMID- 18089661
TI  - The effectiveness of a motivation programme for lifestyle change in the course of
      aortocoronary bypass graft surgery.
AB  - OBJECTIVE: To evaluate the effectiveness of a motivation programme the motivation
      for lifestyle change in patients was measured before and after coronary artery
      bypass graft (CABG) surgery by comparing a usual care group with a group
      attending a motivation programme. DESIGN: Prospective controlled study. SETTING:
      University hospital cardiothoracic surgery department. SUBJECTS: One hundred and
      forty patients (mean age 64.9; SD 8.5 years) who had an elective CABG surgery.
      INTERVENTIONS: Each patient was evaluated regarding his or her motivation for
      lifestyle change two days before and 10 days after CABG surgery. Between January
      and May 2002 patients in usual care were investigated as a control group (n=70).
      From January to May 2003 patients had the opportunity to take part in a
      motivation programme that was provided by a trained clinical psychologist (n =
      70). The programme consists of both personalized single sessions and group
      lectures. MEASURES: A 30-item questionnaire measuring the six factors
      Vulnerability, Intention, Social expectation, Outcome expectation, Self-efficacy
      expectation, and Perceived severity was developed. RESULTS: ANOVA procedures with
      repeated measurements indicate significant effects in terms of higher motivation
      for lifestyle change in the treatment group in Vulnerability (F(1, 138) = 4.04;
      P=0.04), Intention (F(1, 138) = 19.81; P<0.001), Social expectation (F(1,
      138)=21.97; P<0.001), Outcome expectation (F(1, 138) =17.95; P<0.001), and Self
      efficacy expectation (F(1, 138) =14.31; P<0.001). CONCLUSIONS: This motivation
      programme performed in a cardiac surgery hospital after CABG may increase the
      motivation for a positive lifestyle change.

PMID- 18089662
TI  - How do I sound to me? Perceived changes in communication in Parkinson's disease.
AB  - OBJECTIVE: To examine self and carer perceived changes in communication
      associated with Parkinson's disease and relate these to speech intelligibility,
      gender, age and other disease measures. DESIGN: Cross-sectional survey of a
      hospital- and community-based sample of 176 people with Parkinson's disease and
      their carers using a questionnaire based on semantic differential techniques.
      PARTICIPANTS: One hundred and four people with Parkinson's disease with no
      history of communication difficulties prior to onset of their Parkinson's disease
      and 45 primary carers who returned completed questionnaires. MAIN OUTCOME
      MEASURES: Differences in ratings for ;before' the onset of Parkinson's disease
      versus present status. RESULTS: There was a strong perception of negative impact
      on communication between 'before' and 'now', irrespective of age and gender and
      largely independent of disease severity and duration, intelligibility and
      cognitive status. Activities of daily living (assessed by Unified Parkinson's
      Disease Rating Scale (UPDRS) II) and depression rating scale scores had the
      strongest association with change (adjusted R(2) 0.27). There was a significant
      correlation between the rank order of perceived change in features examined in
      people with Parkinson's disease versus their carers, though in general carers
      rated change as having less impact. CONCLUSIONS: Parkinson's disease exercises a
      strong influence on communication even before apparent alterations to
      intelligibility or motor status (UPDRS).

PMID- 18089663
TI  - Self-rated competency in activities predicts functioning and participation one
      year after traumatic brain injury.
AB  - OBJECTIVE: To investigate whether the Patient Competency Rating Scale at three
      months predicts global functioning and participation one year after traumatic
      brain injury. DESIGN: Prospective cohort study with follow-up at 3 and 12 months
      post injury. The Patient Competency Rating Scale was analysed in a logistic
      regression model with the outcomes Community Integration Questionnaire, Glasgow
      Outcome Scale Extended and return to work/study. SETTING: The neurosurgical
      department of a trauma referral centre in a metropolitan hospital. SUBJECTS: A
      cohort of 70 patients with acute traumatic brain injury, ranging from mild to
      severe injury. MAIN MEASURES: The Patient Competency Rating Scale, assessing
      competency in activities, was applied as a predictor. Outcomes describing
      community participation at 12 months were the Community Integration Questionnaire
      and return to work/study. Global functioning was evaluated by the Glasgow Outcome
      Scale Extended. RESULTS: Factor analysis of the Patient Competency Rating Scale
      items yielded three domains: activities demanding cognition,
      interpersonal/emotional skills, and activities of daily living (ADL) competency.
      The first two of these domains significantly predicted return to work/study and
      community integration, whilst global functioning at one year was predicted by
      interpersonal/emotional competency. CONCLUSIONS: The Patient Competency Rating
      Scale at three months predicted functioning and participation one year after
      traumatic brain injury. This indicates that rehabilitation interventions should
      focus on cognitive and interpersonal competency in order to enhance participation
      after traumatic brain injury.

PMID- 18089665
TI  - Acupuncture trial with indistinguishable exposures is moot.

PMID- 18089670
TI  - Early diagnosis of multiple sclerosis-still a challenge?

PMID- 18089671
TI  - Through the eyes of a child: research insights gained through the study of
      childhood multiple sclerosis.

PMID- 18089672
TI  - Worsening of symptoms is associated with lower physical activity levels in
      individuals with multiple sclerosis.
AB  - The present study examined the relationship between the worsening of symptoms
      across a 3-5-year period of time and self-reported physical activity in a sample
      of 51 individuals with multiple sclerosis (MS). Of the 51 participants, 35
      reported a worsening of symptoms over the 3-5-year period of time. The worsening
      of symptoms was associated with significantly and moderately lower levels of self
      reported physical activity independent of depression and EDSS scores and MS
      disease course (P=0.04). This study provides novel evidence that a worsening of
      symptoms is associated with lower levels of physical activity in individuals with
      MS.

PMID- 18089673
TI  - Preparation and evaluation of porous poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate) hydroxyapatite composite scaffolds.
AB  - Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and PHBHHx-hydroxyapatite
      (HAP) composite scaffolds have been prepared by phase separation and subsequent
      sublimation of the solvent for bone tissue engineering. Scanning electron
      microscopy (SEM), porosity measurement, mechanical tests, and thermogravimertric
      analysis (TGA) are used to analyze the physical properties of the scaffolds. The
      biocompatibility and osteoconductivity are assessed by examining the morphology,
      proliferation, and differentiation of MC3T3-E1 osteoprogenitor cells seeded on
      the scaffolds. The PHBHHx-HAP composite scaffolds show better mechanical
      properties, biocompatibility, and osteoconductivity than the PHBHHx scaffolds.
      The results suggest that PHBHHx-HAP composite scaffolds can be employed as a
      promising candidate for bone reconstruction.

PMID- 18089675
TI  - Why don't lupus patients catch cold?

PMID- 18089674
TI  - Long-term evaluation of porous PEGT/PBT implants for soft tissue augmentation.
AB  - Porous PEGT/PBT implants with different physico-chemical characteristics were
      evaluated to identify its potential as biodegradable and biofunctional soft
      tissue filler. Implants (50 x 10 x 5 mm3) were implanted subcutaneously in mini
      pigs and tissue response, tissue volume generated and its consistency were
      assessed quantitatively with a 52 weeks follow-up. The absence of wound edema,
      skin irritation, and chronic inflammation demonstrated biocompatibility of all
      implants evaluated. The hydrophobic implants induced the mildest foreign body
      response, generated highest amount of connective tissue and demonstrated a
      decrease in copolymer MW of 34-37% compared to 90% decrease of the hydrophilic
      implants. The rate and extent of copolymer fragmentation seems to be the
      determining factor of success of soft tissue augmentation using porous PEGT/PBT
      copolymer implants.

PMID- 18089676
TI  - Review: vitamin D, immunity and lupus.
AB  - The identification of vitamin D receptor in cells involved in the immune response
      and the discovery that activated dendritic cells produce vitamin D hormone
      suggested that vitamin D could exert immunoregulatory effects. Patients with
      autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and systemic
      lupus erythematosus (SLE) show low 25-OH vitamin D serum levels. In particular,
      SLE patients have multiple risk factors for vitamin D deficiency and disease
      severity seems correlated with lower 25-OH vitamin D serum levels. Treatment of
      vitamin D deficiency could be particularly important in SLE patients due to
      concomitant insults on their tissues such as bone, and in view of the possible
      immunomodulatory effects exerted by vitamin D.

PMID- 18089677
TI  - Influence of aspirin on the clinical outcomes of 103 anti-phospholipid antibodies
      positive patients.
AB  - One hundred and three consecutive asymptomatic anti-phospholipid (aPL) antibody
      positive carriers, taking aspirin (n=75) or not (n=28), were studied
      retrospectively to determine whether aspirin could provide primary prevention of
      anti-phospholipid syndrome (APS) symptoms. All patients positive for anti
      cardiolipin antibodies (aCL; >25 UGPL or UMPL) and/or lupus anti-coagulant were
      followed for a mean of 64+/-24.7 months.Among aPL-positive patients, 37 had
      systemic lupus erythematosus (SLE), 20 had prolonged activated partial
      thromboplastin times, 19 had other connective tissue diseases, 16 had autoimmune
      thrombocytopenia (AIT), 11 had diverse diseases. Nineteen patients experienced
      thrombotic event(s) during follow-up. Clinical features, biological parameters
      and hydroxychloroquine use were comparable for the two groups, but thrombotic
      events differed (log-rank test; P=0.02). Four of the 10 SLE patients not taking
      aspirin developed thrombosis compared with 3/27 SLE patients taking aspirin (log
      rank test; P=0.03). Anti-phospholipid -positive patients with AIT developed fewer
      thromboses while taking aspirin (log-rank test; P=0.01). In conclusion, aPL
      positive SLE and AIT patients should take aspirin to prevent APS manifestations.
      Prospective therapeutic trials are needed to confirm aspirin's prophylactic role
      in such patients.

PMID- 18089678
TI  - Proteomic analysis of autoantibodies in neuropsychiatric systemic lupus
      erythematosus patient with white matter hyperintensities on brain MRI.
AB  - The pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) may be
      related to autoantibody-mediated neural dysfunction, vasculopathy and
      coagulopathy. We encountered an NPSLE patient whose brain showed characteristic
      diffuse symmetrical hyperintensity lesions in the cerebral white matter,
      cerebellum and middle cerebellar peduncles on T2-weighted magnetic resonance (MR)
      images. In this study, we investigated all the antigens that reacted strongly
      with autoantibodies in this patient's serum by two-dimensional electrophoresis
      (2DE), followed by western blotting (WB) and liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) using rat brain proteins as the antigen source. As a
      result, we identified four antigens as beta-actin, alpha-internexin, 60 kDa heat
      shock protein (Hsp60) and glial fibrillary acidic protein (GFAP). There are
      several reports on the detection of anti-endothelial cell antibodies (AECAs) in
      an SLE patients. Recently, one of the antigens reacting with AECAs in SLE
      patient's sera has been identified as human Hsp60. We speculated that the
      abnormal findings on brain MR images of our patient may be due to impairment of
      microcirculation associated with vascular endothelial cell injury mediated by the
      antibody against Hsp60. This proteomic analysis is a useful tool for identifying
      autoantigens in autoimmune diseases involving autoantibodies.

PMID- 18089679
TI  - Flow cytometric assessment of anti-neuronal antibodies in central nervous system
      involvement of systemic lupus erythematosus and other autoimmune diseases.
AB  - The objective of this study is to evaluate the association between anti-neuronal
      antibody (anti-NA) and central nervous system (CNS) manifestations of systemic
      lupus erythematosus (SLE) and other rheumatic diseases using a flow cytometric
      method. Anti-NA was measured by flow cytometry in serum and cerebrospinal fluid
      (CSF) samples from patients with SLE (n=44 for serum, n=17 for CSF), other
      rheumatic diseases (n=64 for serum, n=21 for CSF) and from healthy controls (n=65
      for serum, n=18 for CSF). Serum anti-NA was more frequently observed in SLE
      (31.8%, 14/44) than in other rheumatic diseases (4.7%, 3/64, P<0.001) or in
      healthy controls (0%, 0/65, P<0.00001). In SLE patients, the frequency of serum
      anti-NA was significantly higher in CNS-SLE (76.5%, 13/17) than in non CNS-SLE
      (3.7%, 1/27, P<0.000001). CSF anti-NA was detected in 88.2% (15/17) of CNS-SLE
      and was more frequently detected in CNS-SLE (15/17, 88.2%) than in other
      rheumatic diseases with CNS involvement (1/21, 4.8%, P<0.000001) or in healthy
      controls (0/18, P<0.000001). In conclusion, serum anti-NA was more frequently
      found in CNS-SLE than in non CNS-SLE, other rheumatic diseases or in healthy
      controls. The frequency of CSF anti-NA in CNS-SLE was significantly higher than
      in other rheumatic diseases with CNS involvement or in healthy controls.

PMID- 18089680
TI  - Striking alteration of some populations of T/B cells in systemic lupus
      erythematosus: relationship to expression of CD62L or some chemokine receptors.
AB  - Recent studies have revealed new populations of T/B cells, including
      central/effector memory, follicular T cells and CXCR3+ or CXCR4+ B cells. In the
      present study, changes in these populations of CD4+ T cells were examined on the
      basis of the expression of CD62L, CCR7 and CXCR5 in patients with systemic lupus
      erythematosus (SLE) in relation to CCL21 and CXCL10. Changes in CXCR3+, CXCR4+
      and CXCR5+ B cells were also examined. CD62L and various chemokine receptors were
      examined by flow cytometry analysis using monoclonal antibodies, and CCL21 and
      CXCL10 were examined by sandwich enzyme-linked immunosorbent assay. In patients
      with SLE, a decrease of naive T cells and an increase in the ratio of activated
      effector memory T cells were associated with an increase of CCL21 and CXCL10 in
      serum, although the correlation was not significant. An increase in the ratio of
      CXCR3+ B cells was also recognized. These results suggest that naive T cells are
      transferred to lymphoid tissue by CCL21, and that effector memory T cells are
      activated by CXCL10. It is also suggested that B cells responsive to follicular
      helper T cells tend to migrate to inflammatory tissue.

PMID- 18089681
TI  - Decreased CD4+CD25+bright T cells in peripheral blood of patients with primary
      Sjogren's syndrome.
AB  - CD4+CD25+bright T cells played a crucial role in the suppression of immune
      response. Recently, decreased levels of CD4+CD25+bright T cells in the peripheral
      blood of patients with systemic lupus erythematosus were reported, suggesting the
      potential role of CD4+CD25+bright T cells in human autoimmune diseases. Primary
      Sjogren's syndrome (pSS) is another common human systemic autoimmune disease. The
      present study aimed to investigate the levels of CD4+CD25+bright T cells in pSS
      and to correlate their levels with some biomarkers of inflammation and immune
      activation. Thirty-three patients with pSS and 35 age- and sex-matched normal
      individuals were enrolled in the study. The flowcytometric method was applied in
      the measurement of CD4+CD25+bright T cells. The results showed that patients with
      pSS had statistically lower levels of CD4+CD25+bright T cells than normal
      controls, expressed either as absolute cell numbers (mean+/-SD: 47.07+/-25.53
      cells/mm3 versus 79.55+/-34.56 cells/mm3, P<0.001) or as percentages of
      peripheral blood mononuclear cells (mean+/-SD: 2.79+/-1.06% versus 3.84+/-1.42%,
      P<0.001) or as percentages of CD4+ T cells (mean+/-SD: 7.85+/-2.62% versus
      11.68+/-3.78%, P<0.005). Moreover, there were statistically significant inverse
      correlations between the levels of CD4+CD25+bright T cells and some parameters of
      inflammation or immune activation including erythrocyte sedimentation rate, C
      reactive protein, IgG and rheumatoid factors. The result suggested that
      CD4+CD25+bright T cells were likely to play anti-inflammatory and
      immunosuppressive roles in the pathogenesis of pSS. However, the exact functions
      of decreased circulating CD4+CD25+bright T cells in pSS need further elucidated.

PMID- 18089682
TI  - Mycophenolate mofetil as the primary treatment of membranous lupus nephritis with
      and without concurrent proliferative disease: a retrospective study of 29 cases.
AB  - Studies of immunosuppressive therapy, particularly mycophenolate mofetil (MMF),
      in membranous lupus nephritis (MLN) are limited. We report on our experience with
      primary (first-line) MMF therapy to induce and sustain renal remission in MLN
      with and without a concurrent proliferative lesion. Systemic lupus erythematosus
      (SLE) patients were studied, retrospectively, if treated with MMF for newly
      diagnosed MLN. Complete remission was defined as proteinuria less than 0.5 g/24
      h, inactive urine sediment and normal estimated glomerular filtration rate.
      Response in pure MLN (Group I, n=10) was compared with mixed MLN and
      proliferative lupus nephritis (Group II, n=19). By 12 months, 4 (40%) patients in
      Group I and 7 (36.8%) in Group II achieved complete remission (P=0.87). One (10%)
      patient in Group I and 2 (10.5%) in Group II had worsening renal disease
      (P=0.97). Mean time to remission was more than seven months in both groups. The
      remaining patients had stable disease without improvement or worsening. Only 2 of
      11 achieving initial remission had a relapse with an average of 28 months of
      follow-up after remission. Self-limited gastrointestinal symptoms occurred in 12
      patients, none requiring withdrawal of the drug. Mycophenolate mofetil as a
      primary therapy in MLN was successful in inducing complete remission in about 40%
      of MLN, particularly in patients with mild proteinuria. However, 12 months of
      therapy was necessary for best outcomes. Response rate was not different in the
      presence or absence of a proliferative lesion.

PMID- 18089683
TI  - Obstructive uropathy as the only manifestation of flare in a patient with
      systemic lupus erythematosus and anti-phospholipid syndrome.
AB  - Chronic interstitial cystitis and ureteral stenosis has occasionally been
      reported in systemic lupus erythematosus, mostly associated with gastrointestinal
      symptoms. We report a case of obstructive uropathy associated to chronic
      interstitial cystitis as the only manifestation of lupus flare in a patient with
      SLE and anti-phospholipid syndrome (APS) who had been in remission for many
      years. The development of chronic interstitial cystitis in patients with SLE and
      APS has not been previously reported. Histopathological study of her urinary
      bladder and ureteral meatus showed chronic inflammatory infiltrate in the
      subepithelium. Lack of significant lower urinary tract symptoms and
      gastrointestinal involvement were some of the factors that could have prevented
      an earlier diagnosis. Obstructive uropathy and renal insufficiency initially
      improved with immunosuppressive treatment and endoureteral protheses, but poor
      compliance to the therapy led to ominous ending.

PMID- 18089684
TI  - Effect of rituximab on clinical and laboratory features of antiphospholipid
      syndrome: a case report and a review of literature.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by a
      hypercoagulable state related to persistently elevated levels of antiphospholipid
      antibodies (aPL). Current treatment for APS is only partially effective and new
      therapies are strongly needed. We report on a case of a 50 years old man with APS
      who suffered from recurrent thromboembolic episodes despite conventional
      anticoagulant treatment. Eight years after the first thrombotic manifestation he
      was diagnosed with a large B cell non-Hodgkin lymphoma. Treatment with CHOP
      (cyclophosphamide, doxorubicin, vincristine and prednisone) plus rituximab was
      started with partial clinical remission of lymphoma and normalization of aPL
      levels with a three years follow-up period free of thrombotic episodes.A review
      of the literature revealed that only 12 case reports on the use of rituximab in
      patients with primary, secondary and catastrophic APS have been published.
      Current knowledge clearly suggests the need for clinical trials to evaluate the
      effect of rituximab in the treatment of resistant APS.

PMID- 18089685
TI  - Long-term outcome of Chinese patients with membranous lupus nephropathy.
AB  - A retrospective analysis of the long-term outcome of patients with membranous
      lupus nephropathy (MLN) was conducted. One hundred Chinese patients, 90 females
      and 10 males with a mean age of 32+/-9 years, with systemic lupus erythematosus
      and biopsy-proven MLN (ISN/RPS2003 classification criteria) were enrolled in this
      study. The patient and renal survivals were estimated by the Kaplan-Meier method
      and the risk factors associated with end-stage renal failure (ESRF) were assessed
      by the Cox proportional hazards regression analysis. The mean follow-up of all
      patients was 77.6+/-56 months. During follow-up, two patients died. Patient
      survival at 5 and 10 years was 98%. Renal survival at 5 and 10 years was 96.1%
      and 92.7%, respectively. Severe tubular-intersticial lesion (HR 66.514),
      nephrotic range proteinuria (HR 19.159) and refractoriness to treatments (HR
      9.834) were independent risk factors for developing ESRF. Three of the six
      patients with ESRF had severe tubular-interstitial lesions on initial biopsy.
      Twenty-one patients underwent a repeat biopsy after 33months' (median time)
      follow-up, eight (38.1%) of these (class V superimposed class IV in 5, class V
      superimposed class III in 2 and class VI in 1) had transformed and three (37.5%)
      of them progressed to ESRF. Complications included infection (13%), thrombosis
      (3%), avascular necrosis (3%), diabetes mellitus (4%) and skin cancer (1%). The
      rate of patient and renal survival was high in this group of patients with MLN.

PMID- 18089686
TI  - Clinical and immunological manifestations in 151 SLE patients living in Dubai.
AB  - To gain better understanding of systemic lupus erythematosus (SLE) in Dubai we
      studied the clinical and immunological manifestations in a cohort of 151 patients
      attended Rheumatology Clinic in Dubai Hospital between January 2002 and January
      2007. We found that the female to male ratio was 20.5:1, with a mean age of 35.5
      years (0.9). The mean age at disease onset was 28.9 years (0.8) and mean disease
      duration 6.7 years (0.4). Five-year survival rate in our cohort was 94%. The
      commonest clinical manifestations in this cohort were arthritis (88%),
      haematological abnormalities (61.6%), and malar rash (60.3%). Leucopenia, fever,
      hair loss and proteinuria were observed in approximately half of the patients.
      Anaemia was found in 44.3% but only 9.9% had haemolytic anaemia. Photosensitive
      rash was seen in 43% of patients. Approximately one-third of the patients had
      serositis and mouth ulcers, 30.5 and 27.2% respectively. Vasculitis was observed
      in 19.2% of patients. Neuropsychiatric manifestations (15.9%), discoid lupus
      lesions (12.6%), and brain infarcts (13.2%) were infrequent. Subacute cutaneous
      lupus (6%) was also uncommon. Anti-nuclear antibodies were detected in 98%, anti
      double stranded DNA antibodies in 88.7%, anti-Sm antibodies in 19.7%, anti-RNP in
      40.4%, anti-Ro antibodies in 52.3% and anti-La antibodies in 19.8%. Anti
      cardiolipin IgM and IgG were detected in 25.3 and 22.4%, respectively. This study
      suggests that Arabs with SLE residing in Dubai have comparable clinical features
      to their counterparts in other Arab countries and Western countries. The high
      prevalence of positive anti-Ro antibodies among our Arab patients probably
      reflects a character, that is, commonly seen in SLE patients of Middle East
      origin.

PMID- 18089687
TI  - Life-threatening systemic flare-up of systemic lupus erythematosus following
      influenza vaccination.

PMID- 18089688
TI  - Rituximab for the treatment of thrombotic thrombocytopenic purpura in systemic
      lupus erythematosus.

PMID- 18089689
TI  - Systemic lupus erythematosus complicated with aortitis.

PMID- 18089690
TI  - Reduced adipogenic gene expression in thigh adipose tissue precedes human
      immunodeficiency virus-associated lipoatrophy.
AB  - CONTEXT: The expression of adipogenic genes in sc adipose tissue has been
      reported to be lower among patients with HIV-associated lipoatrophy than HIV
      uninfected controls. It is unclear whether this is a result or cause of
      lipoatrophy. OBJECTIVE: The objective of the study was to investigate the
      temporal relationships among changes in adipogenic gene expression in sc adipose
      tissue and changes in body fat distribution and metabolic complications in HIV
      infected subjects on antiretroviral therapy. DESIGN: This was a prospective
      longitudinal study. SETTING: The study was conducted at HIV clinics in Seattle,
      Washington. PARTICIPANTS: The study population included 31 HIV-infected and 12
      control subjects. INTERVENTIONS: Subjects were followed up for 12 months after
      they initiated or modified their existing antiretroviral regimen. MAIN OUTCOME
      MEASURES: Changes in body composition, plasma lipids, insulin sensitivity, and
      gene expression in sc abdominal and thigh adipose tissue. RESULTS: Subjects who
      developed lipoatrophy (n=10) had elevated fasting triglycerides [3.16 (sd 2.79)
      mmol/liter] and reduced insulin sensitivity as measured by frequently sampled iv
      glucose tolerance test [1.89 (sd 1.27)x10(-4) min(-1)/microU.ml] after 12 months,
      whereas those without lipoatrophy (n=21) did not show any metabolic complications
      [triglycerides 1.32 (sd 0.58) mmol/liter, P=0.01 vs. lipoatrophy; insulin
      sensitivity 3.52 (sd 1.91)x10(-4) min(-1)/microU.ml, P=0.01 vs. lipoatrophy]. In
      subjects developing lipoatrophy, the expression of genes involved in adipocyte
      differentiation, lipid uptake, and local cortisol production in thigh adipose
      tissue was significantly reduced already at the 2-month visit, several months
      before any loss of extremity fat mass was evident. CONCLUSIONS: In HIV-infected
      subjects, lipoatrophy is associated with elevated fasting triglycerides and
      insulin resistance and might be caused by a direct or indirect effect of
      antiretroviral drugs on sc adipocyte differentiation.

PMID- 18089691
TI  - Vitamin D2 is as effective as vitamin D3 in maintaining circulating
      concentrations of 25-hydroxyvitamin D.
AB  - CONTEXT: Two reports suggested that vitamin D2 is less effective than vitamin D3
      in maintaining vitamin D status. OBJECTIVE: Our objective was to determine
      whether vitamin D2 was less effective than vitamin D3 in maintaining serum 25
      hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D3.
      SUBJECTS AND DESIGN: This was a randomized, placebo-controlled, double-blinded
      study of healthy adults ages 18-84 yr who received placebo, 1000 IU vitamin D3,
      1000 IU vitamin D2, or 500 IU vitamin D2 plus 500 IU vitamin D3 daily for 11 wk
      at the end of the winter. RESULTS: Sixty percent of the healthy adults were
      vitamin D deficient at the start of the study. The circulating levels of 25
      hydroxyvitamin D (mean+/-sd) increased to the same extent in the groups that
      received 1000 IU daily as vitamin D2 (baseline 16.9+/-10.5 ng/ml; 11 wk 26.8+/
      9.6 ng/ml), vitamin D3 (baseline 19.6+/-11.1 ng/ml; 11 wk 28.9+/-11.0 ng/ml), or
      a combination of 500 IU vitamin D2 and 500 IU vitamin D3 (baseline 20.2+/-10.4
      ng/ml; 11 wk 28.4+/-7.7 ng/ml). The 25-hydroxyvitamin D3 levels did not change in
      the group that received 1000 IU vitamin D2 daily. The 1000 IU dose of vitamin D2
      or vitamin D3 did not raise 25-hydroxyvitamin D levels in vitamin D-deficient
      subjects above 30 ng/ml. CONCLUSION: A 1000 IU dose of vitamin D2 daily was as
      effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels
      and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore,
      vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin
      D status.

PMID- 18089692
TI  - Prevalence and determinants of elevated apolipoprotein B and dense low-density
      lipoprotein in youths with type 1 and type 2 diabetes.
AB  - OBJECTIVE: The objective of the study was to assess the prevalence and
      determinants of elevated apolipoprotein B (apoB) and dense low-density
      lipoprotein (LDL) in United States youth with type 1 or type 2 diabetes. METHODS:
      We conducted cross-sectional analyses of apoB concentrations, LDL density, and
      prevalence of elevated apoB levels and dense LDL from the SEARCH for Diabetes in
      Youth study, a six-center U.S.-based study of youth with diabetes onset younger
      than 20 years of age (2657 with type 1 and 345 with type 2). RESULTS: Among youth
      with type 1 diabetes, 11% had elevated apoB (>or=100 mg/dl, 1.95 mm/liter), 8%
      had dense LDL (relative flotation rate<or=0.237), and 12% had elevated LDL
      cholesterol (>or=130 mg/dl, 3.36 mm/liter). In contrast, among youth with type 2
      diabetes, 36% had elevated apoB, 36% had dense LDL, but only 23% had elevated LDL
      cholesterol. Dense LDL and apoB each increased with hemoglobin A1c in both types.
      Among type 1 diabetics in poor glycemic control (hemoglobin A1c>or=9.5%), 28% had
      elevated apoB, and 18% had dense LDL, whereas 72% of poorly controlled type 2
      diabetics had elevated apoB and 62% had dense LDL. CONCLUSIONS: In youth with
      type 1 diabetes, elevated apoB and dense LDL were not highly prevalent, whereas
      elevated apoB and dense LDL were common lipoprotein abnormalities in youth with
      type 2 diabetes. The prevalence of these risk factors substantially increased
      with poor glycemic control in both groups, stressing the importance of achieving
      and maintaining an optimal glucose control.

PMID- 18089693
TI  - Global adiposity rather than abnormal regional fat distribution characterizes
      women with polycystic ovary syndrome.
AB  - CONTEXT: Obesity-related predisposition to polycystic ovary syndrome (PCOS) could
      reflect overall adiposity and/or regional accumulation of abdominal visceral fat.
      OBJECTIVE: The objective of the study was to compare distributions of visceral,
      abdominal sc, and gluteofemoral sc adipose tissue in PCOS cases vs. control
      women. DESIGN: This was a cross-sectional study. SETTING AND PARTICIPANTS: Fat
      depot measurements from axial magnetic resonance imaging scans taken at
      anatomically predefined sites were compared between 22 body mass index (BMI)/fat
      mass-matched pairs of PCOS cases and controls; whole-group comparisons included
      50 PCOS cases vs. 28 female controls. All subjects were of UK British/Irish
      origin. MAIN OUTCOME MEASURE(S): We measured cross-sectional areas of adipose
      tissue within visceral (mid-L4), abdominal (mid-L4) sc, and gluteofemoral
      (greater trochanteric and midfemoral) sc fat depots. Other measurements included
      fat mass, BMI, testosterone, SHBG, and homeostasis model assessment of insulin
      resistance (a measure of insulin sensitivity). Whole-group analyses were adjusted
      for fat mass and age. RESULTS: There were no significant differences in fat-depot
      measurements between BMI/fat mass-matched pairs of PCOS cases and controls: mid
      L4 visceral (P=0.40), abdominal sc (P=0.22), gluteal sc (P=0.67), and midfemoral
      sc (P=0.37) depots. Whole-group comparisons gave similar results after
      adjustments for fat mass and age. Fasting serum insulin concentrations (P=0.03)
      and homeostasis model assessment of insulin resistance (P=0.03) were
      significantly higher in the PCOS group than BMI/fat mass-matched controls.
      CONCLUSIONS: PCOS cases and BMI/fat mass-matched control women are
      indistinguishable with respect to distribution of fat within visceral, abdominal
      sc, and gluteofemoral sc depots, despite significant differences in insulin
      resistance between these two groups.

PMID- 18089694
TI  - Calpain-10 gene and protein expression in human skeletal muscle: effect of acute
      lipid-induced insulin resistance and type 2 diabetes.
AB  - OBJECTIVE: Our objective was to investigate the effect of lipid-induced insulin
      resistance and type 2 diabetes on skeletal muscle calpain-10 mRNA and protein
      levels. RESEARCH DESIGN AND METHODS: In the first part of this study, 10 healthy
      subjects underwent hyperinsulinemic euglycemic (4.5 mmol/liter) clamps for 6 h
      with iv infusion of either saline or a 20% Intralipid emulsion (Fresenius Kabi
      AG, Bad Homburg, Germany). Skeletal muscle biopsies were taken before and after 3
      and 6-h insulin infusion and analyzed for calpain-10 mRNA and protein
      expression. In the second part of the study, muscle samples obtained after an
      overnight fast in 10 long-standing, sedentary type 2 diabetes patients, 10
      sedentary, weight-matched, normoglycemic controls, and 10 age-matched, endurance
      trained cyclists were analyzed for calpain-10 mRNA and protein content. RESULTS:
      Intralipid infusion in healthy subjects reduced whole body glucose disposal by
      approximately 50% (P<0.001). Calpain-10 mRNA (P=0.01) but not protein content was
      reduced after 6-h insulin infusion in both the saline and Intralipid emulsion
      trials. Skeletal muscle calpain-10 mRNA and protein content did not differ
      between the type 2 diabetes patients and normoglycemic controls, but there was a
      strong trend for total calpain-10 protein to be greater in the endurance-trained
      athletes (P=0.06). CONCLUSIONS: These data indicate that skeletal muscle calpain
      10 expression is not modified by insulin resistance per se and suggest that
      hyperinsulinemia and exercise training may modulate human skeletal muscle calpain
      10 expression.

PMID- 18089695
TI  - Endocrine and radiological studies in patients with molecularly confirmed CHARGE
      syndrome.
AB  - CONTEXT: CHARGE syndrome is a complex of congenital malformations, and CHD7 has
      been reported as a major gene involved in the etiology. OBJECTIVE: We performed
      endocrine and radiological studies to determine whether endocrinological
      disorders such as hypogonadotropic hypogonadism, GH deficiency, or hypothyroidism
      are involved and also whether olfactory bulb hypoplasia and semicircular canal
      aplasia are major signs in patients with molecularly confirmed CHARGE syndrome.
      DESIGN: Clinical features, endocrinological assessments, and radiological
      abnormalities in eight children (five boys and three girls) whose molecular
      analyses were available were evaluated among 15 children clinically diagnosed
      with CHARGE syndrome at our institute. RESULTS: We identified heterozygous CHD7
      mutations in all patients screened for mutations. Four boys had micropenis and/or
      cryptorchidism. One was diagnosed with GH deficiency, and the other was diagnosed
      with hypothyroidism. Computed tomography findings revealed aplasia of the
      semicircular canals. Magnetic resonance imaging studies of the olfactory bulb
      region revealed abnormal olfactory sulci and bulb development in all children.
      CONCLUSION: We suggest that hypogonadism, GH deficiency, and hypothyroidism could
      be possible endocrinological defects in patients with CHD7 mutations and that
      olfactory bulb hypoplasia as well as semicircular canal aplasia should be
      considered as a major sign for CHARGE syndrome and recommend a computed
      tomography scan of the temporal bone and magnetic resonance imaging study of the
      olfactory bulb region.

PMID- 18089696
TI  - Early detection of insulin sensitivity and beta-cell function with simple tests
      indicates future derangements in late pregnancy.
AB  - OBJECTIVE: Insulin sensitivity and secretion during early and late pregnancy were
      assessed in women with normal glucose tolerance and gestational diabetes mellitus
      (GDM). RESEARCH DESIGN AND METHODS: The oral glucose tolerance test (OGTT) was
      performed in 903 women at 16-20th gestational week, of whom 37 had GDM (GDM1
      group), and 859 repeated the OGTT at wk 26-30. At the second test, 55 had GDM
      (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity
      from OGTT (as quantitative insulin sensitivity check index and OGTT insulin
      sensitivity) and beta-cell function (as the ratio of the areas under the insulin
      and glucose concentration curves, adjusted for insulin sensitivity) were assessed
      in both tests. RESULTS: In early pregnancy the quantitative insulin sensitivity
      check index was not different in the three groups, whereas OGTT insulin
      sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late
      pregnancy both indices were reduced in GDM compared with ND and lower than in
      early pregnancy. In early pregnancy GDM1, but not GDM2, had lower beta-cell
      function than ND. During the late visit, GDM2 also showed impaired beta-cell
      function compared with ND; furthermore, the adaptation to the increase to insulin
      resistance from early to late pregnancy was defective in GDM2. CONCLUSIONS: In
      early pregnancy insulin sensitivity, as assessed from the OGTT but not from
      fasting measurements, is impaired in women who developed GDM. beta-Cell function
      impairment is evident only when GDM is manifest and is characterized by
      inappropriate adaptation to the pregnancy induced increase in insulin resistance.

PMID- 18089697
TI  - Prognostic indicators of changes in bone density measures in adolescent girls
      with anorexia nervosa-II.
AB  - INTRODUCTION: Adolescents with anorexia nervosa (AN) have low bone mineral
      density (BMD). Baseline predictors of temporal BMD changes (DeltaBMD) in AN,
      including 1) gastrointestinal peptides regulating food intake and appetite that
      have been related to bone metabolism and 2) bone turnover markers, have not been
      well characterized. We hypothesized that baseline levels of nutritionally
      regulated hormones and of bone turnover markers would predict DeltaBMD overall.
      METHODS: In a prospective observational study, lumbar and whole-body BMD was
      measured at 0, 6, and 12 months in 34 AN girls aged 12-18 yr and 33 controls.
      Baseline body mass index, lean mass, nutritionally regulated hormones [IGF-I,
      cortisol, ghrelin, leptin, and peptide YY (PYY)], bone formation, and resorption
      markers were examined to determine nutritional and hormonal predictors of bone
      density changes. RESULTS: In a regression model, baseline ghrelin and PYY
      predicted changes in spine bone measures; and baseline ghrelin, cortisol, and PYY
      predicted changes in whole-body bone measures independent of baseline nutritional
      status. CONCLUSIONS: Neuroendocrine gastrointestinal-derived peptides regulating
      food intake are independent predictors of changes in bone mass in AN.

PMID- 18089698
TI  - Preimplantation genetic diagnosis for severe albright hereditary osteodystrophy.
AB  - CONTEXT: Preimplantation genetic diagnosis (PGD) enables the selection of embryos
      without mutations for implantation and has not been described to our knowledge
      for mutations in GNAS. Phocomelia in a patient with Albright hereditary
      osteodystrophy (AHO) has also not been previously described. OBJECTIVE: The aim
      of this study was to identify a GNAS mutation in a patient with a severe form of
      AHO and pseudohypoparathyroidism type 1a with phocomelia and to perform PGD on
      embryos derived by in vitro fertilization to deliver an unaffected infant.
      DESIGN: A proband and his family are described clinically, the GNAS gene was
      sequenced to identify a novel mutation in the proband, and PGD was performed on
      embryos. SETTING: The setting was in a tertiary-care hospital. PATIENTS: The
      patients were from a single family in which the proband has a severe form of AHO.
      INTERVENTIONS: Interventions were PGD and in vitro fertilization. MAIN OUTCOME
      MEASURES: The main outcome measures were the clinical phenotypes and GNAS gene
      sequences of the proband, embryos, and family members. RESULTS: After PGD, three
      genotypically normal embryos were transferred back to the mother. Pregnancy
      ensued, and a healthy male infant was delivered at 36.5 wk gestation. The GNAS
      genes in the baby were confirmed as wild-type, and the infant is free of any
      signs of AHO. CONCLUSIONS: We describe herein a proband with AHO and severe
      skeletal deformities (including phocomelia) related to a novel GNAS mutation and
      the delivery of a male infant with homozygous normal GNAS genotype after PGD.

PMID- 18089699
TI  - Type I Gaucher disease, a glycosphingolipid storage disorder, is associated with
      insulin resistance.
AB  - CONTEXT: Complex glycosphingolipids, in majority the ganglioside GM3, surround
      the insulin receptor in a special membrane compartment (raft) and modulate
      signaling through this receptor. Increased levels of GM3 in rafts impair insulin
      signaling, resulting in insulin resistance. Gaucher disease is a lysosomal
      storage disorder in which impaired breakdown of glucosylceramide leads to its
      accumulation in macrophages. Secondary to this defect, GM3 concentrations, for
      which glucosylceramide is the precursor, in plasma and several cell types are
      elevated. OBJECTIVE: We studied the influence of glycosphingolipid storage on
      whole body glucose and fat metabolism by measuring insulin-mediated (IMGU) and
      noninsulin-mediated glucose uptake (NIMGU) and suppression of free fatty acids by
      insulin. DESIGN AND MAIN OUTCOME MEASURES: We studied six Gaucher patients,
      either naive to treatment or with considerable remaining burden of disease, and
      six matched healthy control subjects in the basal state, during an euglycemic and
      a hyperglycemic clamp with somatostatin measuring NIMGU and during an euglycemic
      hyperinsulinemic clamp measuring IMGU, using stable isotopes. RESULTS: NIMGU
      (both during euglycemia and hyperglycemia) did not differ between patients and
      control subjects. IMGU was lower in Gaucher patients, compared with controls.
      Suppression of lipolysis by insulin tended to be less effective in Gaucher
      patients. CONCLUSION: Gaucher disease, a lysosomal glycosphingolipid storage
      disorder, is associated with (peripheral) insulin resistance, possibly through
      the influence of glycosphingolipids on insulin receptor functioning.

PMID- 18089700
TI  - Early development of visceral fat excess after spontaneous catch-up growth in
      children with low birth weight.
AB  - CONTEXT: The sequence of prenatal growth restraint and infantile catch-up of
      weight is by the age of 4 yr associated with hyperinsulinemic adiposity. We
      studied whether the adiposity of post-catch-up children born small for
      gestational age (SGA) is further amplified between age 4 and 6 yr and whether
      visceral fat excess has already emerged by the age of 6 yr. SETTING: The study
      took place at a university hospital. STUDY POPULATION AND DESIGN: A longitudinal
      cohort (age 2-6 yr) of 22 children born appropriate for gestational age (AGA) and
      29 born SGA were studied. Auxological, endocrine, metabolic, and body composition
      (by absorptiometry) assessments were made at 2, 4, and 6 yr, and visceral fat was
      assessed (by magnetic resonance imaging) at 6 yr. MAIN OUTCOMES: Outcome measures
      included fasting glucose, insulin, IGF-I, neutrophil to lymphocyte ratio, lean
      mass, and total, abdominal, and visceral fat mass. RESULTS: Between ages 4-6 yr,
      the relative adiposity of SGA children was further amplified. Between ages 2-6
      yr, SGA children gained more total and abdominal fat and raised their insulin,
      IGF-I, and neutrophil to lymphocyte ratio more than did AGA children (all
      P<0.0001). At age 6 yr, the average amount of visceral fat was in SGA children
      more than 50% higher than in AGA children (P<0.005). The 0- to 2-yr increment in
      weight Z-score together with the 2- to 6-yr increment in fasting insulin
      accounted for 62% of visceral fat variability at age 6 yr. CONCLUSION: The amount
      of visceral fat is in post-catch-up SGA children excessive by the age of 6 yr. In
      populations at risk for type 2 diabetes or metabolic syndrome after fetal growth
      restraint, the time window for early intervention may have to be advanced into
      prepubertal childhood.

PMID- 18089701
TI  - Effects of calcium and vitamin D supplementation on hip bone mineral density and
      calcium-related analytes in elderly ambulatory Australian women: a five-year
      randomized controlled trial.
AB  - CONTEXT: Effects of long-term calcium, with or without vitamin D, on hip bone
      mineral density (BMD) and bone turnover in sunny climates have not been reported.
      OBJECTIVE: The aim was to evaluate the effect of vitamin D added to calcium
      supplementation on hip dual-energy x-ray absorptiometry BMD and calcium-related
      analytes. DESIGN, SETTING, AND PARTICIPANTS: The study was a 5-yr randomized,
      controlled, double-blind trial of 120 community-dwelling women aged 70-80 yr.
      INTERVENTIONS: The interventions were 1200 mg/d calcium with placebo vitamin D
      (Ca group) or with 1000 IU/d vitamin D2 (CaD group), or double placebo (control).
      MAIN OUTCOME MEASURES: Hip BMD, plasma 25-hydroxyvitamin D, biomarkers of bone
      turnover, PTH, and intestinal calcium absorption were measured. RESULTS: Hip BMD
      was preserved in CaD (-0.17%) and Ca (0.19%) groups but not controls (-1.27%) at
      yr 1 and maintained in the CaD group only at yr 3 and 5. The beneficial effects
      were mainly in those with baseline 25-hydroxyvitamin D levels below the median
      (68 nmol/liter). At yr 1, compared with controls, the Ca and CaD groups had 6.8
      and 11.3% lower plasma alkaline phosphatase, respectively (P<or=0.02), and 28.7
      and 34.5% lower urinary deoxypyridinoline to creatinine ratio, respectively
      (P<or=0.05). At 5 yr, this suppression was maintained only in the CaD group. CaD
      reduced PTH at 3 and 5 yr cf. controls (27.8 and 31.3%, P<or=0.005) in those with
      baseline PTH levels above the median (3.6 pmol/liter). Therapy did not affect
      intestinal calcium absorption at high carrier loads. CONCLUSIONS: Addition of
      vitamin D to calcium has long-term beneficial effects on bone density in elderly
      women living in a sunny climate, probably mediated by a long-term reduction in
      bone turnover rate.

PMID- 18089702
TI  - Weight gain and restoration of menses as predictors of bone mineral density
      change in adolescent girls with anorexia nervosa-1.
AB  - CONTEXT: Adolescents with anorexia nervosa (AN) have low bone mineral density.
      However, the effect of disease recovery, first, on bone density measures assessed
      using the Molgaard approach, which differentiates between reported low bone
      density resulting from short bones (based on height Z-scores) and that resulting
      from thin bones [based on measures of bone area (BA) for height] or light bones
      [based on measures of bone mineral content (BMC) for BA]; and second, on height
      adjusted bone density measures, has not been well characterized. We hypothesized
      that menstrual recovery and weight gain (> or =10% increase in body mass index)
      would predict an increase in these measures of bone density. METHODS: In a
      prospective observational study, lumbar and whole-body (WB) bone density was
      measured at 0, 6, and 12 months in 34 AN girls aged 12-18 yr and 33 controls.
      Using Ward's modification of the Molgaard approach, we determined measures of BMC
      for BA and BA for height at the lumbar spine and WB and also determined spine
      bone mineral apparent density and WB BMC adjusted for height. RESULTS: Girls with
      AN had lower spine BMC for BA Z-scores (P = 0.0009), and lower WB BA for height Z
      (P < 0.0001), compared with controls. Menstrual recovery and weight gain in AN
      (AN-recovered) (median 9 months) resulted in a stabilization of BMD measures,
      whereas BMD continued to decrease in AN who did not gain weight and recover
      menses (AN-not recovered). AN-recovered also predicted greater increases in spine
      BMC for BA and WB BA for height, compared with AN-not recovered (P < 0.05).
      CONCLUSIONS: Even short-term weight gain with menstrual recovery is associated
      with a stabilization of BMD measures.

PMID- 18089703
TI  - Pituitary and/or peripheral estrogen-receptor alpha regulates follicle
      stimulating hormone secretion, whereas central estrogenic pathways direct growth
      hormone and prolactin secretion in postmenopausal women.
AB  - BACKGROUND: Estradiol (E(2)) stimulates GH and prolactin secretion and suppresses
      FSH secretion in postmenopausal women. Whether central nervous system (CNS) or
      pituitary mechanisms (or both) mediate such actions is not known. OBJECTIVE: Our
      objective was to distinguish between hypothalamic and pituitary or peripheral
      (hepatic) actions of E2. SETTING: This study was performed in an academic medical
      center. DESIGN: This was a double-blind, prospectively randomized, placebo (Pl)
      controlled study. METHODS: The capability of a selective, noncompetitive, non-CNS
      permeant estrogen receptor (ER)-alpha antagonist, fulvestrant (FUL) to antagonize
      the effects of transdermal E2 and Pl on GH, prolactin, and FSH secretion was
      assessed in 43 women (ages 50-80 yr) in a four parallel-cohort study. Each woman
      received four secretagogue infusions to stimulate GH secretion. IGF-I and its
      binding proteins were measured secondarily. RESULTS: Administration of Pl/E2
      increased GH and prolactin concentrations by 100%, and suppressed FSH
      concentrations by more than 50% (each P<or=0.004 compared with Pl/Pl). Treatment
      with FUL/E2 compared with Pl/E2 partially relieved estrogen's inhibition of FSH
      secretion (P=0.041), without altering E2's stimulation of prolactin secretion.
      ANOVA further revealed that: 1) estrogen milieu (P=0.014) and secretagogue type
      (P<0.001) each determined GH concentrations; 2) FUL/Pl suppressed IGF-I
      concentrations (P<0.001); 3) FUL abrogated estrogen's elevation of IGF binding
      protein-1 concentrations (P<0.001); and 4) FUL did not oppose estrogen's
      suppression of IGF binding protein-3 concentrations (P<0.001). SUMMARY AND
      CONCLUSIONS: Responses to a non-CNS permeant ERalpha antagonist indicate that E2
      inhibits FSH secretion in part via pituitary/peripheral ERalpha, drives prolactin
      output via nonpituitary/nonperipheral-ERalpha effects, and directs GH secretion
      and IGF-I-binding proteins by complex mechanisms.

PMID- 18089704
TI  - Feasibility of low-dose coronary CT angiography: first experience with
      prospective ECG-gating.
AB  - AIMS: To determine the feasibility of prospective electrocardiogram (ECG)-gating
      to achieve low-dose computed tomography coronary angiography (CTCA). METHODS AND
      RESULTS: Forty-one consecutive patients with suspected (n = 35) or known coronary
      artery disease (n = 6) underwent 64-slice CTCA using prospective ECG-gating.
      Individual radiation dose exposure was estimated from the dose-length product.
      Two independent readers semi-quantitatively assessed the overall image quality on
      a five-point scale and measured vessel attenuation in each coronary segment. One
      patient was excluded for atrial fibrillation. Mean effective radiation dose was
      2.1 +/- 0.6 mSv (range, 1.1-3.0 mSv). Image quality was inversely related to
      heart rate (HR) (57.3 +/- 6.2, range 39-66 b.p.m.; r = 0.58, P < 0.001), vessel
      attenuation (346 +/- 104, range 110-780 HU; r = 0.56, P < 0.001), and body mass
      index (26.1 +/- 4.0, range 19.1-36.3 kg/m(2); r = 0.45, P < 0.001), but not to HR
      variability (1.5 +/- 1.0, range 0.2-5.1 b.p.m.; r = 0.28, P = 0.069). Non
      diagnostic CTCA image quality was found in 5.0% of coronary segments. However,
      below a HR of 63 b.p.m. (n = 28), as determined by receiver operator
      characteristic curve, only 1.1% of coronary segments were non-diagnostic compared
      with 14.8% with HR of >63 b.p.m. (P < 0.001). CONCLUSION: This first experience
      documents the feasibility of prospective ECG-gating for CTCA with diagnostic
      image quality at a low radiation dose (1.1-3.0 mSv), favouring HR <63 b.p.m.

PMID- 18089705
TI  - In vitro expansion of human breast cancer epithelial and mesenchymal stromal
      cells: optimization of a coculture model for personalized therapy approaches.
AB  - Molecularly targeted, customized therapies are designed based on the molecular
      portraits of cancer tissue. The efficacy of targeted therapy in individual
      patients depends on the contribution of single individual cancer cells within the
      context of their microenvironment. We have developed an in vitro model of human
      mammary epithelial-stromal cocultures to answer specific clinical questions
      related to breast cancer, to provide a tool with which to identify a signature in
      each breast tumor, and to identify the metabolic molecular targets of therapy in
      an attempt to optimize the efficacy of targeted therapy in each patient. Fifty
      five human breast cancer samples were obtained through surgery. Epithelial and
      stromal cells were isolated from tissue specimens by differential centrifugation,
      and cryopreserved. Western blot analysis and RT-PCR were used to identify the
      tissue-specific expression patterns of cancer cells. Dose-response curves were
      constructed for the aromatase inhibitor formestane and for herceptin, and a 3
      (4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay was done for combined
      treatment. We collected and cryopreserved, for future use, viable living cells
      from 55 breast tumor specimens from which we derived short-term cocultures. The
      presence of cytokeratins and vimentin was evaluated in 20 samples, and pHER2/neu
      and aromatase were evaluated in 4 cocultures. Formestane and herceptin had a
      cumulative growth-inhibitory effect on cocultures expressing epidermal growth
      factor receptors and aromatase. The in vitro model of human mammary epithelial
      stromal cocultures reported herein can be used to examine, and to store, a
      patient's tumor-derived, living cells that retain the characteristics of the
      mother-tissue and respond, in vitro, to therapy.

PMID- 18089706
TI  - Inactivation of glycogen synthase kinase-3beta contributes to brain-derived
      neutrophic factor/TrkB-induced resistance to chemotherapy in neuroblastoma cells.
AB  - Elucidating signaling pathways that mediate cell survival or apoptosis will
      facilitate the development of targeted therapies in cancer. In neuroblastoma
      tumors, brain-derived neurotrophic factor (BDNF) and its receptor TrkB are
      associated with poor prognosis. Our previous studies have shown that BDNF
      activation of TrkB induces resistance to chemotherapy via activation of
      phosphoinositide-3-kinase (PI3K)/Akt pathway. To study targets of PI3K/Akt that
      mediate protection from chemotherapy, we focused on glycogen synthase kinase
      3beta (GSK-3beta), which is a known modulator of apoptosis. We used pharmacologic
      and genetic methods to study the role of GSK-3beta in the BDNF/TrkB/PI3K/Akt
      protection of neuroblastoma from chemotherapy. BDNF activation of TrkB induced
      the Akt-dependent phosphorylation of GSK-3beta, resulting in its inactivation.
      Treatment of neuroblastoma cells with inhibitors of GSK-3beta, LiCl, GSK-3beta
      inhibitor VII, kenpaullone, or a GSK-3beta-targeted small interfering RNA (siRNA)
      resulted in a 15% to 40% increase in neuroblastoma cell survival after cytotoxic
      treatment. Transfection of neuroblastoma cells with a constitutively active GSK
      3beta S9A9 caused a 10% to 15% decrease in cell survival. Using real-time,
      dynamic measurements of cell survival, we found that 6 to 8 h after etoposide
      treatment was the period during which critical events regulating the induction of
      cell death or BDNF/TrkB-induced protection occurred. During this period,
      etoposide treatment was associated with the dephosphorylation and activation of
      GSK-3beta in the mitochondria that was blocked by BDNF activation of TrkB. These
      data indicate that the inactivation of GSK-3beta contributes to the
      BDNF/TrkB/PI3K/Akt protection of neuroblastoma cells from chemotherapy.

PMID- 18089707
TI  - Chemical synthesis and biological evaluation of a NAD(P)H:quinone oxidoreductase
      1 targeted tripartite quinone drug delivery system.
AB  - NAD(P)H:quinone oxidoreductase-1 (NQO1) is a potential target for therapeutic
      intervention but attempts to exploit NQO1 using quinone-based bioreductive
      prodrugs have been largely compromised by toxicity to organs that inherently
      express high levels of NQO1. In an attempt to circumvent this problem, this study
      describes the development of a tripartite quinone-based drug delivery system, the
      ultimate objective of which is to release a targeted therapeutic agent following
      the reduction of a quinone "trigger" by NQO1. Molecular modeling of drug/NQO1
      interactions were conducted prior to the synthesis of N-{4-[bis-(2-chloroethyl)
      amino]-phenyl}-beta,beta,2,4,5-pentamethyl-3,6-dioxo-1,4-cyclohexadiene-1
      propanamide (prodrug 1). Prodrug 1 is a good substrate for purified NQO1 (V(max)
      and K(m) values of 11.86 +/- 3.09 micromol/min/mg and 2.70 +/- 1.14 micromol/L,
      respectively) and liquid chromatography-mass spectrometry analysis of the
      metabolites generated showed that lactone 3 and aniline mustard 4 were generated
      in a time- and NQO1-dependent manner. Chemosensitivity studies showed that
      prodrug 1 is selectively toxic to cells that overexpress NQO1 under aerobic
      conditions, and comet assay analysis confirmed the presence of elevated
      interstrand cross-links in NQO1-rich compared with NQO1-deficient cells. Hypoxic
      sensitization (hypoxic cytotoxicity ratio = 15.8) was observed in T47D cells that
      overexpress cytochrome P450 reductase. In conclusion, the results of this study
      provide mechanistic proof of principle that a tripartite benzoquinone drug
      delivery system is enzymatically reduced to release an active therapeutic agent.
      Further development of this concept to fine-tune substrate specificity for
      specific reductases and/or the inclusion of alternative therapeutic agents is
      warranted.

PMID- 18089708
TI  - Antineoplastic agents target the 25-hydroxyvitamin D3 24-hydroxylase messenger
      RNA for degradation: implications in anticancer activity.
AB  - Calcitriol or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] has antitumor activity
      and hence its levels in patients may play an important role in disease outcome.
      Here, we report that the antineoplastic agents, daunorubicin hydrochloride,
      etoposide, and vincristine sulfate inhibited the ability of 1,25(OH)(2)D(3) to
      cause the accumulation of mRNA for kidney 25-hydroxyvitamin D(3) 24-hydroxylase
      (CYP24), an enzyme which catabolizes this hormone. This was not due to a drug
      induced cytotoxic effect, reduction in the expression of the vitamin D receptor
      or inhibition of the vitamin D receptor-mediated activation of the mitogen
      activated protein kinases or CYP24 promoter activity. Interestingly, there was
      selective degradation of CYP24 mRNA in the presence of the drugs. This was
      accompanied by an enhancement in the levels of 1,25(OH)(2)D(3) in cells incubated
      with 25-hydroxy vitamin D(3). These data identify a novel mechanism of action of
      some commonly used antineoplastic agents which by decreasing the stability of
      CYP24 mRNA would prolong the bioavailability of 1,25(OH)(2)D(3) for anticancer
      actions.

PMID- 18089709
TI  - Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo
      quantification of biological activity.
AB  - The Aurora family of serine/threonine kinases is important for the regulation of
      centrosome maturation, chromosome segregation, and cytokinesis during mitosis.
      Overexpression of Aurora kinases in mammalian cells leads to genetic instability
      and transformation. Increased levels of Aurora kinases have also been linked to a
      broad range of human tumors. Here, we describe the properties of CCT129202, a
      representative of a structurally novel series of imidazopyridine small-molecule
      inhibitors of Aurora kinase activity. This compound showed high selectivity for
      the Aurora kinases over a panel of other kinases tested and inhibits
      proliferation in multiple cultured human tumor cell lines. CCT129202 causes the
      accumulation of human tumor cells with >or=4N DNA content, leading to apoptosis.
      CCT120202-treated human tumor cells showed a delay in mitosis, abrogation of
      nocodazole-induced mitotic arrest, and spindle defects. Growth of HCT116
      xenografts in nude mice was inhibited after i.p. administration of CCT129202. We
      show that p21, the cyclin-dependent kinase inhibitor, is induced by CCT129202. Up
      regulation of p21 by CCT129202 in HCT116 cells led to Rb hypophosphorylation and
      E2F inhibition, contributing to a decrease in thymidine kinase 1 transcription.
      This has facilitated the use of 3'-deoxy-3'[(18)F]fluorothymidine-positron
      emission tomography to measure noninvasively the biological activity of the
      Aurora kinase inhibitor CCT129202 in vivo.

PMID- 18089710
TI  - PHA-739358, a potent inhibitor of Aurora kinases with a selective target
      inhibition profile relevant to cancer.
AB  - PHA-739358 is a small-molecule 3-aminopyrazole derivative with strong activity
      against Aurora kinases and cross-reactivities with some receptor tyrosine kinases
      relevant for cancer. PHA-739358 inhibits all Aurora kinase family members and
      shows a dominant Aurora B kinase inhibition-related cellular phenotype and
      mechanism of action in cells in vitro and in vivo. p53 status-dependent
      endoreduplication is observed upon treatment of cells with PHA-739358, and
      phosphorylation of histone H3 in Ser(10) is inhibited. The compound has
      significant antitumor activity in different xenografts and spontaneous and
      transgenic animal tumor models and shows a favorable pharmacokinetic and safety
      profile. In vivo target modulation is observed as assessed by the inhibition of
      the phosphorylation of histone H3, which has been validated preclinically as a
      candidate biomarker for the clinical phase. Pharmacokinetics/pharmacodynamics
      modeling was used to define drug potency and to support the prediction of active
      clinical doses and schedules. We conclude that PHA-739358, which is currently
      tested in clinical trials, has great therapeutic potential in anticancer therapy
      in a wide range of cancers.

PMID- 18089711
TI  - The transcription factor FOXO3a is a crucial cellular target of gefitinib
      (Iressa) in breast cancer cells.
AB  - Gefitinib is a specific inhibitor of the epidermal growth factor receptor (EGFR)
      that causes growth delay in cancer cell lines and human tumor xenografts
      expressing high levels of EGFR. An understanding of the downstream cellular
      targets of gefitinib will allow the discovery of biomarkers for predicting
      outcomes and monitoring anti-EGFR therapies and provide information for key
      targets for therapeutic intervention. In this study, we investigated the role of
      FOXO3a in gefitinib action and resistance. Using two gefitinib-sensitive (i.e.,
      BT474 and SKBR3) as well as three other resistant breast carcinoma cell lines
      (i.e., MCF-7, MDA-MB-231, and MDA-MB-453), we showed that gefitinib targets the
      transcription factor FOXO3a to mediate cell cycle arrest and cell death in
      sensitive breast cancer cells. In the sensitive cells, gefitinib treatment causes
      cell cycle arrest predominantly at the G(0)-G(1) phase and apoptosis, which is
      associated with FOXO3a dephosphorylation at Akt sites and nuclear translocation,
      whereas in the resistant cells, FOXO3a stays phosphorylated and remains in the
      cytoplasm. The nuclear accumulation of FOXO3a in response to gefitinib was
      confirmed in tumor tissue sections from breast cancer patients presurgically
      treated with gefitinib as monotherapy. We also showed that knockdown of FOXO3a
      expression using small interfering RNA (siRNA) can rescue sensitive BT474 cells
      from gefitinib-induced cell-proliferative arrest, whereas reintroduction of
      active FOXO3a in resistant MDA-MB-231 cells can at least partially restore cell
      proliferative arrest and sensitivity to gefitinib. These results suggest that the
      FOXO3a dephosphorylation and nuclear localization have a direct role in mediating
      the gefitinib-induced proliferative arrest and in determining sensitivity to
      gefitinib.

PMID- 18089712
TI  - Chemosensitization of head and neck cancer cells by PUMA.
AB  - Head and neck squamous cell carcinoma (HNSCC) ranks the eighth most common cancer
      worldwide. The patients often present with advanced disease, which responds
      poorly to chemoradiation therapy. PUMA is a BH3-only Bcl-2 family protein and a
      p53 target that is required for apoptosis induced by p53 and various
      chemotherapeutic agents. In this study, we found that PUMA induction by
      chemotherapeutic agents is abrogated in most HNSCC cell lines. Adenoviral gene
      delivery of PUMA induced apoptosis and chemosensitization more potently than did
      adenoviral delivery of p53 in HNSCC cells. Finally, we showed that PUMA
      suppressed the growth of HNSCC xenograft tumors and sensitized them to cisplatin
      through induction of apoptosis. Our data suggest that absence of PUMA activation
      in HNSCC cells contributes to chemoresistance and that gene therapy with PUMA
      might be an efficient substitute for p53 to enhance the responses of HNSCC cells
      to chemotherapy.

PMID- 18089713
TI  - Cell type-- dependent effects of Polo-like kinase 1 inhibition compared with
      targeted polo box interference in cancer cell lines.
AB  - Multiple critical roles within mitosis have been assigned to Polo-like kinase 1
      (Plk1), making it an attractive candidate for mitotic targeting of cancer cells.
      Plk1 contains two domains amenable for targeted interference: a kinase domain
      responsible for the enzymatic function and a polo box domain necessary for
      substrate recognition and subcellular localization. Here, we compare two
      approaches for targeted interference with Plk1 function, either by a Plk1 small
      molecule enzyme inhibitor or by inducible overexpression of the polo box in human
      cancer cell lines. Inducible expression of the Plk1 polo box resulted in growth
      inhibition of RKOp27 human colon adenocarcinoma cells without obvious signs of
      mitotic abnormalities. A Plk1 kinase inhibitor in the same cell line arrested
      cells in mitosis with subsequent onset of apoptosis. Similarly, PC-3 human
      prostate cancer cells were growth inhibited on expression of the polo box.
      Prolonged expression of the polo box in these cells resulted in the occurrence of
      binucleated or multinucleated cells. In contrast, U2OS human osteosarcoma cells
      responded to overexpression of the polo box with a massive mitotic accumulation
      coinciding with the onset of apoptosis. Comparison of spindle formation revealed
      very similar mitotic abnormalities in polo box-overexpressing U2OS cells compared
      with U2OS cells treated with the Plk1 kinase inhibitor. We conclude that
      interference with polo box function and inhibition of Plk1 kinase activity can
      exert very similar phenotypic effects in certain cell lines but highly
      contrasting effects in others. This may point to subtle differences in the
      molecular machinery of mitosis regulation in cancer cells.

PMID- 18089715
TI  - A novel, potent, and specific ephrinA1-based cytotoxin against EphA2 receptor
      expressing tumor cells.
AB  - We have previously shown that the EphA2 receptor tyrosine kinase is overexpressed
      in glioblastoma multiforme (GBM) and represents a novel, attractive therapeutic
      target for the treatment of brain tumors. Here, we have developed an EphA2
      targeted agent, ephrinA1-PE38QQR, a novel cytotoxin composed of ephrinA1, a
      ligand for EphA2, and PE38QQR, a mutated form of Pseudomonas aeruginosa exotoxin
      A. EphrinA1-PE38QQR showed potent and dose-dependent killing of GBM cells
      overexpressing the EphA2 receptor in cell viability and clonogenic survival
      assays, with an average IC(50) of approximately 10(-11) mol/L. The conjugate was
      also highly effective in killing breast and prostate cancer cells overexpressing
      EphA2. The cytotoxic effect of ephrinA1-PE38QQR was specific, as it was
      neutralized by an excess of EphA2 ligands. Moreover, normal human endothelial
      cells and breast cancer cells that do not overexpress EphA2, as well as GBM cells
      that have down-regulated EphA2, were not susceptible to the cytotoxin. EphrinA1
      PE38QQR-mediated cytotoxicity induced caspase-dependent apoptosis, which was,
      however, not responsible for cell death in response to the conjugate. In
      addition, the conjugate elicited no changes in the activity of survival pathways
      such as phosphoinositide 3-kinase, measured by AKT phosphorylation. This is the
      first attempt to create a cytotoxic therapy using any of the ephrin ligands of
      either class (A or B) conjugated to a bacterial toxin. EphrinA1-PE38QQR is very
      potent and specific, produces cell death that is caspase independent, and forms
      the basis for the further development of clinically applicable EphA2-targeted
      cytotoxins.

PMID- 18089714
TI  - TRA-8 anti-DR5 monoclonal antibody and gemcitabine induce apoptosis and inhibit
      radiologically validated orthotopic pancreatic tumor growth.
AB  - PURPOSE: To evaluate agonistic TRA-8 monoclonal antibody to human death receptor
      5 (DR5) and gemcitabine in vitro and in an orthotopic pancreatic cancer model.
      EXPERIMENTAL DESIGN: Pancreatic cancer cell lines were screened for DR5
      expression, cytotoxicity, and apoptosis induced by TRA-8, gemcitabine, or
      gemcitabine and TRA-8. An orthotopic model of pancreatic cancer was established
      in severe combined immunodeficient mice. Mice were treated with TRA-8,
      gemcitabine, or a combination for one or two cycles of therapy. Tumor growth
      (ultrasound) and survival were analyzed. RESULTS: All five pancreatic cancer cell
      lines showed DR5 protein expression and varying sensitivity to TRA-8-mediated
      cytotoxicity. MIA PaCa-2 cells were very sensitive to TRA-8, moderately resistant
      to gemcitabine, with additive cytotoxicity to the combination. S2-VP10 cells were
      resistant to TRA-8 and sensitive to gemcitabine with synergistic sensitivity to
      the combination. Combination treatment in vitro produced enhanced caspase-3 and
      caspase-8 activation. A single cycle of therapy produced comparable efficacy for
      single-agent TRA-8 and the combination of TRA-8 and gemcitabine, with significant
      reduction in tumor size and prolonged survival compared with gemcitabine alone or
      control animals. With two cycles of therapy, TRA-8 and combination therapy
      produced enhanced inhibition of tumor growth compared with single-agent
      gemcitabine or untreated animals. However, the combination regimen showed
      enhanced survival as compared with single-agent TRA-8. CONCLUSIONS: Pancreatic
      cancer cell lines express varying levels of DR5 and differ in their sensitivity
      to TRA-8 and gemcitabine-induced cytotoxicity. TRA-8 with two cycles of
      gemcitabine therapy produced the best overall survival.

PMID- 18089716
TI  - Novel E-ring camptothecin keto analogues (S38809 and S39625) are stable, potent,
      and selective topoisomerase I inhibitors without being substrates of drug efflux
      transporters.
AB  - Camptothecin (CPT) analogues are powerful anticancer agents but are chemically
      unstable due to their alpha-hydroxylactone six-membered E-ring structure, which
      is essential for trapping topoisomerase I (Top1)-DNA cleavage complexes. To
      stabilize the E-ring, CPT keto analogues with a five-membered E-ring lacking the
      oxygen of the lactone ring (S38809 and S39625) have been synthesized. S39625 has
      been selected for advanced preclinical development based on its promising
      activity in tumor models. Here, we show that both keto analogues are active
      against purified Top1 and selective against Top1 in yeast and human cancer cells.
      The keto analogues show improved cytotoxicity toward colon, breast, and prostate
      cancer cells and leukemia cells compared with CPT. The drug-induced Top1-DNA
      cleavage complexes induced by the keto analogues show remarkable persistence both
      with purified Top1 and in cells following 1-h drug treatments. Moreover, we find
      that S39625 is not a substrate for either the ABCB1 (multidrug resistance-1/P
      glycoprotein) or ABCG2 (mitoxantrone resistance/breast cancer resistance protein)
      drug efflux transporters, which sets S39625 apart from the clinically used CPT
      analogues topotecan or SN-38 (active metabolite of irinotecan). Finally, we show
      that nanomolar concentrations of S38809 or S39625 induce intense and persistent
      histone gamma-H2AX. The chemical stability of the keto analogues and the ability
      of S39625 to produce high levels of persistent Top1-DNA cleavage complex and its
      potent antiproliferative activity against human cancer cell lines make S39625 a
      promising new anticancer drug candidate. Histone gamma-H2AX could be used as a
      biomarker for the upcoming clinical trials of S39625.

PMID- 18089717
TI  - Efficacy and tissue distribution of DHP107, an oral paclitaxel formulation.
AB  - Paclitaxel is indispensable in treating human cancers. Due to poor drug
      solubility and efflux systems in the gastrointestinal tract, peroral delivery of
      paclitaxel has been a significant challenge. We developed a mucoadhesive oral
      formulation (DHP107) that can directly and effectively deliver paclitaxel to
      intestinal endothelial cells without concomitant use of P-glycoprotein
      inhibitors. Here, we evaluated the tissue distribution of paclitaxel, the
      antitumor efficacy and the absorption mechanism of DHP107. DHP107, which contains
      10 mg/mL of paclitaxel in a mixture of monoolein, tricarprylin, and Tween 80 was
      administered p.o. to female BALB/c mice at a 50 mg/kg dose. Diluted Taxol was
      administered via bolus tail-vein injection at 10 mg/kg as a control. Blood and
      tissue samples were harvested at various time points and analyzed by high
      performance liquid chromatography. Tissue sections were observed using light
      microscopy after immunohistochemical and Oil Red O staining. By day 27, tumor
      volume after DHP107 and Taxol treatments was one-third of that in the untreated
      group. After p.o. administration, paclitaxel was widely distributed in various
      organs (T(max) = 2 h), especially liver, spleen, and lung. DHP107 was effectively
      absorbed through the intestinal lipid transport system. DHP107 changed
      spontaneously into <100-mum droplets and micelles in the intestine, which in turn
      adhered to mucoepithelial cells, were absorbed via lipid uptake mechanism, and
      formed lipid bodies in the epithelium. Paclitaxel in DHP107 was effectively
      absorbed through the gastrointestinal tract via lipid uptake mechanism and was
      distributed in various tissues. The detailed uptake mechanism is currently under
      investigation.

PMID- 18089718
TI  - Chemopreventive effects of silymarin and silibinin on N-butyl-N-(4-hydroxybutyl)
      nitrosamine induced urinary bladder carcinogenesis in male ICR mice.
AB  - Effective strategies are lacking for the management of urinary bladder cancer for
      which smoking is a potential risk factor. Herein, we evaluated chemoprevention of
      urinary bladder cancer by natural chemopreventive agents, silymarin and
      silibinin, in a preclinical animal (ICR mouse) model of bladder cancer induced by
      tobacco smoke carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN). Mice
      were fed p.o. with saline or OH-BBN (0.05%, w/v) in drinking water for 6 weeks or
      with silymarin or silibinin (200 mg/kg body weight for both) starting 1 week
      before OH-BBN exposure for 51 weeks. Silymarin and silibinin strongly arrested OH
      BBN-induced tumor progression at the stage of mucosal dysplasia with a striking
      reduction in papillary nodular dysplasia as well as invasive carcinoma. Some
      silymarin- or silibinin-treated mice developed no urothelial lesions in spite of
      OH-BBN exposure. Immunohistochemical analyses at study conclusion revealed that
      silymarin and silibinin decreased cell proliferation by 42% (P < 0.001) and 44%
      (P < 0.001) and increased apoptosis by 4-fold (P < 0.05) and 6-fold (P < 0.05) in
      OH-BBN-induced urothelium, respectively. Antiproliferative and apoptotic effects
      of silymarin and silibinin were associated with decreases in (a) cyclin D1
      protein level and extracellular signal-regulated kinase-1/2 phosphorylation and
      in (b) protein levels of survivin and nuclear phospho-p65 (Ser(276) and
      Ser(536)), respectively. Together, these results suggest that silymarin and
      silibinin inhibit chemically induced urinary bladder tumor growth and progression
      possibly by inhibiting cell proliferation and enhancing apoptosis.

PMID- 18089719
TI  - Zoledronic acid affects over-angiogenic phenotype of endothelial cells in
      patients with multiple myeloma.
AB  - Therapeutic doses of zoledronic acid markedly inhibit in vitro proliferation,
      chemotaxis, and capillarogenesis of bone marrow endothelial cells of patients
      with multiple myeloma. Zoledronic acid also induces a sizeable reduction of
      angiogenesis in the in vivo chorioallantoic membrane assay. These effects are
      partly sustained by gene and protein inhibition of vascular endothelial growth
      factor and vascular endothelial growth factor receptor 2 in an autocrine loop.
      Mevastatin, a specific inhibitor of the mevalonate pathway, reverts the
      zoledronic acid antiangiogenic effect, indicating that the drug halts this
      pathway. Our results provide evidence of a direct antiangiogenic activity of
      zoledronic acid on multiple myeloma patient-derived endothelial cells due to at
      least four different mechanisms identified either in vitro or in vivo.
      Tentatively, we suggest that the zoledronic acid antitumoral activity in multiple
      myeloma is also sustained by antiangiogenesis, which would partly account for its
      therapeutic efficacy in multiple myeloma.

PMID- 18089720
TI  - Zoledronic acid inhibits osteosarcoma growth in an orthotopic model.
AB  - Zoledronic acid (ZOL) has been shown to reduce osteolysis in bone metastasis. Its
      efficacy in osteosarcoma has not been convincingly proved in a clinically
      relevant model for the disease. In vitro, ZOL decreased osteosarcoma cell
      proliferation, mainly due to an increase in apoptosis in a dose-dependent
      fashion. There was a decrease in cell migration at >or=10 micromol/L
      concentrations, but invasion was inhibited at a much lower dose of 0.1
      micromol/L. Reverse transcription-PCR showed that ZOL overall caused an increased
      expression of osteocalcin and decreased expression of alkaline phosphatase,
      osteopontin, osteonectin, and vascular endothelial growth factor, with no change
      in expression of osteoprotegerin. ZOL administration s.c. twice weekly at 0.12
      mg/kg to SaOS-2 tumor-bearing mice resulted in primary tumor growth inhibition,
      reduction in lung metastases, and dramatic decrease in osteolysis. Furthermore,
      in the ZOL cohort, there was a clear reduction in the number of osteoclasts in
      bone exposed to tumor and a lower tumor vessel density. These data point to the
      adjuvant potential of ZOL in the management of osteosarcoma not only for its
      antiosteolytic properties but also for its ability to directly halt tumor cell
      growth and metastasis via its effects on viability, invasion, differentiation,
      and angiogenesis.

PMID- 18089721
TI  - New inhibitors of ABCG2 identified by high-throughput screening.
AB  - In order to identify novel inhibitors of the ATP-binding cassette transporter,
      ABCG2, a high-throughput assay measuring the accumulation of the ABCG2 substrate
      pheophorbide a in ABCG2-overexpressing NCI-H460 MX20 cells was used to screen
      libraries of compounds. Out of a library of 7,325 natural products and synthetic
      compounds from the National Cancer Institute/Developmental Therapeutics Program
      collection, 18 were found to inhibit ABCG2 at 10 micromol/L. After eliminating
      flavonoids and compounds of limited availability from the 18 original compounds,
      10 of the 11 remaining compounds reversed mitoxantrone resistance in NCI
      H460/MX20 cells and prevented ABCG2-mediated BODIPY-prazosin transport in ABCG2
      transfected HEK293 cells, confirming an interaction with ABCG2. Based on the
      activity profiles and the availability of materials, five inhibitors were
      examined for their ability to compete with [(125)I]iodoarylazidoprazosin labeling
      of ABCG2, increase binding of the anti-ABCG2 antibody 5D3, and prevent P
      glycoprotein or multidrug resistance protein 1-mediated transport. At a
      concentration of 20 micromol/L, all of the compounds reduced
      iodoarylazidoprazosin labeling by 50% to 80% compared with controls. All five
      compounds also increased 5D3 labeling of ABCG2, indicating that these compounds
      are inhibitors but not substrates of ABCG2. None of the compounds affected P
      glycoprotein-mediated rhodamine 123 transport, whereas three affected multidrug
      resistance protein-1-mediated calcein transport at 25 mumol/L, suggesting that
      the compounds are relatively specific for ABCG2. These five novel inhibitors of
      ABCG2 activity may provide a basis for further investigation of ABCG2 function
      and its relevance in multidrug resistance.

PMID- 18089722
TI  - Evidence for dual mode of action of a thiosemicarbazone, NSC73306: a potent
      substrate of the multidrug resistance linked ABCG2 transporter.
AB  - Multidrug resistance due to reduced drug accumulation is a phenomenon
      predominantly caused by the overexpression of members of the ATP-binding cassette
      (ABC) transporters, including ABCB1 (P-glycoprotein), ABCG2, and several ABCC
      family members [multidrug resistance-associated protein (MRP)]. We previously
      reported that a thiosemicarbazone derivative, NSC73306, is cytotoxic to carcinoma
      cells that overexpress functional P-glycoprotein, and it resensitizes these cells
      to chemotherapeutics. In this study, we investigated the effect of NSC73306 on
      cells overexpressing other ABC drug transporters, including ABCG2, MRP1, MRP4,
      and MRP5. Our findings showed that NSC73306 is not more toxic to cells that
      overexpress these transporters compared with their respective parental cells, and
      these transporters do not confer resistance to NSC73306 either. In spite of this,
      we observed that NSC73306 is a transport substrate for ABCG2 that can effectively
      inhibit ABCG2-mediated drug transport and reverse resistance to both mitoxantrone
      and topotecan in ABCG2-expressing cells. Interactions between NSC73306 and the
      ABCG2 drug-binding site(s) were confirmed by its stimulatory effect on ATPase
      activity (140-150 nmol/L concentration required for 50% stimulation) and by
      inhibition of [(125)I]iodoarylazidoprazosin photolabeling (50% inhibition at 250
      400 nmol/L) of the substrate-binding site(s). Overall, NSC73306 seems to be a
      potent modulator of ABCG2 that does not interact with MRP1, MRP4, or MRP5.
      Collectively, these data suggest that NSC73306 can potentially be used, due to
      its dual mode of action, as an effective agent to overcome drug resistance by
      eliminating P-glycoprotein-overexpressing cells and by acting as a potent
      modulator that resensitizes ABCG2-expressing cancer cells to chemotherapeutics.

PMID- 18089723
TI  - Kallikrein-binding protein inhibits growth of gastric carcinoma by reducing
      vascular endothelial growth factor production and angiogenesis.
AB  - Kallikrein-binding protein (KBP) has been identified as an endogenous angiogenic
      inhibitor. We previously showed that KBP inhibited rat retinal neovascularization
      by down-regulation of vascular endothelial growth factor (VEGF) in endothelial
      cells. However, its antiangiogenic potential for inhibition of gastric carcinoma
      and the effect on VEGF in tumor cells have not been elucidated. The present study
      was designed to investigate the effect of KBP on growth of gastric carcinoma and
      the possible molecular mechanism. Recombinant KBP dose dependently inhibited
      proliferation and induced apoptosis of endothelial cells, but no effect on
      proliferation and apoptosis of SGC-7,901 gastric carcinoma cells. I.p. injection
      of KBP resulted in growth inhibition of both heterotopic and orthotopic gastric
      carcinoma xenografts at 61.4% and 52.3%, respectively. Microvessel density in
      tumor tissues treated with KBP was significantly decreased, suggesting that KBP
      suppressed tumor growth by antiangiogenesis. The expression and release of VEGF,
      a major angiogenic stimulator, were down-regulated by KBP in SGC-7,901 cells and
      gastric carcinoma xenografts. RNA levels of VEGF in SGC-7,901 cells were also
      decreased by KBP, thus suggesting the regulation at the transcriptional level.
      Therefore, hypoxia-inducible factor 1alpha (HIF-1alpha), a crucial
      transcriptional factor for VEGF expression, was examined in SGC-7,901 cells
      treated by KBP. KBP reduced HIF-1alpha protein level and nuclear translocation,
      which may be responsible for the down-regulation of VEGF transcription. Down
      regulation of VEGF expression and release in tumor cells through inhibiting HIF
      1alpha, thus attenuating the paracrine effect of VEGF on endothelial cell
      proliferation and vascular permeability in tumor tissues, may represent a novel
      mechanism for the antiangiogenic and antitumor activity of KBP.

PMID- 18089724
TI  - In vitro transport of gimatecan (7-t-butoxyiminomethylcamptothecin) by breast
      cancer resistance protein, P-glycoprotein, and multidrug resistance protein 2.
AB  - Lipophilic camptothecin derivatives are considered to have negligible affinity
      for breast cancer resistance protein (BCRP; ABCG2). Gimatecan, a new orally
      available 7-t-butoxyiminomethyl-substituted lipophilic camptothecin derivative,
      has been previously reported to be not a substrate for BCRP. Using a panel of in
      vitro models, we tested whether gimatecan is a substrate for BCRP as well as for
      P-glycoprotein (MDR1) or multidrug resistance protein 2 (MRP2; ABCC2), ATP
      binding cassette drug efflux transporters involved in anticancer drug resistance,
      and able to affect the pharmacokinetics of substrate drugs. Cell survival, drug
      transport, accumulation, and efflux were studied in IGROV1 and (human BCRP
      overexpressing) T8 cells, Madin-Darby canine kidney II (MDCKII-WT, MDCKII-Bcrp1,
      MDCKII-MDR1, and MDCKII-MRP2), and LLCPK (LLCPK-WT and LLCPK-MDR1) cells.
      Competition with methotrexate uptake was studied in Sf9-BCRP membrane vesicles.
      In vitro, expression of BCRP resulted in 8- to 10-fold resistance to gimatecan.
      In Transwell experiments, gimatecan was transported by Bcrp1 and transport was
      inhibited by the BCRP/P-glycoprotein inhibitors elacridar and pantoprazole.
      Efflux of gimatecan from MDCKII-Bcrp1 cells was faster than in WT cells. In Sf9
      BCRP membrane vesicles, gimatecan significantly inhibited BCRP-mediated transport
      of methotrexate. In contrast, gimatecan was not transported by MDR1 or MRP2.
      Gimatecan is transported by BCRP/Bcrp1 in vitro, although to a lesser extent than
      the camptothecin analogue topotecan. Implications of BCRP expression in the gut
      for the oral development of gimatecan and the interaction between gimatecan and
      other BCRP substrate drugs and/or inhibitors warrant further clinical
      investigation.

PMID- 18089725
TI  - Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic
      lymphoma kinase and c-Met, in experimental models of anaplastic large-cell
      lymphoma.
AB  - A t(2;5) chromosomal translocation resulting in expression of an oncogenic kinase
      fusion protein known as nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) has
      been implicated in the pathogenesis of anaplastic large-cell lymphoma (ALCL). PF
      2341066 was recently identified as a p.o. bioavailable, small-molecule inhibitor
      of the catalytic activity of c-Met kinase and the NPM-ALK fusion protein. PF
      2341066 also potently inhibited NPM-ALK phosphorylation in Karpas299 or SU-DHL-1
      ALCL cells (mean IC(50) value, 24 nmol/L). In biochemical and cellular screens,
      PF-2341066 was shown to be selective for c-Met and ALK at pharmacologically
      relevant concentrations across a panel of >120 diverse kinases. PF-2341066
      potently inhibited cell proliferation, which was associated with G(1)-S-phase
      cell cycle arrest and induction of apoptosis in ALK-positive ALCL cells (IC(50)
      values, approximately 30 nmol/L) but not ALK-negative lymphoma cells. The
      induction of apoptosis was confirmed using terminal deoxyribonucleotide
      transferase-mediated nick-end labeling and Annexin V staining (IC(50) values, 25
      50 nmol/L). P.o. administration of PF-2341066 to severe combined immunodeficient
      Beige mice bearing Karpas299 ALCL tumor xenografts resulted in dose-dependent
      antitumor efficacy with complete regression of all tumors at the 100 mg/kg/d dose
      within 15 days of initial compound administration. A strong correlation was
      observed between antitumor response and inhibition of NPM-ALK phosphorylation and
      induction of apoptosis in tumor tissue. In addition, inhibition of key NPM-ALK
      signaling mediators, including phospholipase C-gamma, signal transducers and
      activators of transcription 3, extracellular signal-regulated kinases, and Akt by
      PF-2341066 were observed at concentrations or dose levels, which correlated with
      inhibition of NPM-ALK phosphorylation and function. Collectively, these data
      illustrate the potential clinical utility of inhibitors of NPM-ALK in treatment
      of patients with ALK-positive ALCL.

PMID- 18089727
TI  - Interferons and viruses: an interplay between induction, signalling, antiviral
      responses and virus countermeasures.
AB  - The interferon (IFN) system is an extremely powerful antiviral response that is
      capable of controlling most, if not all, virus infections in the absence of
      adaptive immunity. However, viruses can still replicate and cause disease in
      vivo, because they have some strategy for at least partially circumventing the
      IFN response. We reviewed this topic in 2000 [Goodbourn, S., Didcock, L. &
      Randall, R. E. (2000). J Gen Virol 81, 2341-2364] but, since then, a great deal
      has been discovered about the molecular mechanisms of the IFN response and how
      different viruses circumvent it. This information is of fundamental interest, but
      may also have practical application in the design and manufacture of attenuated
      virus vaccines and the development of novel antiviral drugs. In the first part of
      this review, we describe how viruses activate the IFN system, how IFNs induce
      transcription of their target genes and the mechanism of action of IFN-induced
      proteins with antiviral action. In the second part, we describe how viruses
      circumvent the IFN response. Here, we reflect upon possible consequences for both
      the virus and host of the different strategies that viruses have evolved and
      discuss whether certain viruses have exploited the IFN response to modulate their
      life cycle (e.g. to establish and maintain persistent/latent infections), whether
      perturbation of the IFN response by persistent infections can lead to chronic
      disease, and the importance of the IFN system as a species barrier to virus
      infections. Lastly, we briefly describe applied aspects that arise from an
      increase in our knowledge in this area, including vaccine design and manufacture,
      the development of novel antiviral drugs and the use of IFN-sensitive oncolytic
      viruses in the treatment of cancer.

PMID- 18089728
TI  - Molecular analysis of avian H7 influenza viruses circulating in Eurasia in 1999
      2005: detection of multiple reassortant virus genotypes.
AB  - Avian influenza infections by high and low pathogenicity H7 influenza viruses
      have caused several outbreaks in European poultry in recent years, also resulting
      in human infections. Although in some cases the source of H7 strains from
      domestic poultry was shown to be the viruses circulating in the wild bird
      reservoir, a thorough characterization of the entire genome of H7 viruses from
      both wild and domestic Eurasian birds, and their evolutionary relationships, has
      not been conducted. In our study, we have analysed low pathogenicity H7 influenza
      strains isolated from wild and domestic ducks in Italy and southern China and
      compared them with those from reared terrestrial poultry such as chicken and
      turkey. Phylogenetic analysis demonstrated that the H7 haemagglutinin genes were
      all closely related to each other, whereas the remaining genes could be divided
      into two or more phylogenetic groups. Almost each year different H7 reassortant
      viruses were identified and in at least two different years more than one H7
      genotype co-circulated. A recent precursor in wild waterfowl was identified for
      most of the gene segments of terrestrial poultry viruses. Our data suggest that
      reassortment allows avian influenza viruses, in their natural reservoir, to
      increase their genetic diversity. In turn this might help avian influenza viruses
      colonize a wider range of hosts, including domestic poultry.

PMID- 18089729
TI  - Protective effect of low-concentration chlorine dioxide gas against influenza A
      virus infection.
AB  - Influenza virus infection is one of the major causes of human morbidity and
      mortality. Between humans, this virus spreads mostly via aerosols excreted from
      the respiratory system. Current means of prevention of influenza virus infection
      are not entirely satisfactory because of their limited efficacy. Safe and
      effective preventive measures against pandemic influenza are greatly needed. We
      demonstrate that infection of mice induced by aerosols of influenza A virus was
      prevented by chlorine dioxide (ClO(2)) gas at an extremely low concentration
      (below the long-term permissible exposure level to humans, namely 0.1 p.p.m.).
      Mice in semi-closed cages were exposed to aerosols of influenza A virus (1
      LD(50)) and ClO(2) gas (0.03 p.p.m.) simultaneously for 15 min. Three days after
      exposure, pulmonary virus titre (TCID(50)) was 10(2.6+/-1.5) in five mice treated
      with ClO(2), whilst it was 10(6.7+/-0.2) in five mice that had not been treated
      (P=0.003). Cumulative mortality after 16 days was 0/10 mice treated with ClO(2)
      and 7/10 mice that had not been treated (P=0.002). In in vitro experiments,
      ClO(2) denatured viral envelope proteins (haemagglutinin and neuraminidase) that
      are indispensable for infectivity of the virus, and abolished infectivity. Taken
      together, we conclude that ClO(2) gas is effective at preventing aerosol-induced
      influenza virus infection in mice by denaturing viral envelope proteins at a
      concentration well below the permissible exposure level to humans. ClO(2) gas
      could therefore be useful as a preventive means against influenza in places of
      human activity without necessitating evacuation.

PMID- 18089730
TI  - Histone modifications associated with herpes simplex virus type 1 genomes during
      quiescence and following ICP0-mediated de-repression.
AB  - In the current study, it was shown that repressed virus genomes in quiescently
      infected MRC5 cells adopt a repressed histone-associated structure marked by the
      enrichment of deacetylated histones at a wide variety of herpes simplex virus
      type 1 (HSV-1) promoters. In addition, it was shown that genome de-repression,
      mediated by HSV-2 superinfection or delivery of ICP0 using a recombinant
      adenovirus vector, resulted in the enrichment of acetylated histones on HSV DNA.
      These data indicate that ICP0-mediated genome de-repression is intimately linked
      to enrichment of acetylated histones at virus promoters. The fold change in
      association of pan-acetylated histone H3 following Ad.TRE.ICP0-mediated de
      repression consistently revealed promoter-specific variation, with the highest
      fold changes (>50-fold) being observed at the latency-associated transcript
      promoter and enhancer regions. Chromatin immunoprecipitation analyses using an
      antibody specific to the C terminus of histone H3 as a surrogate measure of
      nucleosome occupancy revealed little variability in the total loading of histone
      H3 at the various HSV promoters. This observation suggests that acetylation of
      histone H3 in response to ICP0 expression is not uniformly targeted across the
      HSV-1 genome during ICP0-mediated de-repression.

PMID- 18089731
TI  - Dendritic cell-induced apoptosis of human cytomegalovirus-infected fibroblasts
      promotes cross-presentation of pp65 to CD8+ T cells.
AB  - An efficient host response to human cytomegalovirus (HCMV) infection may depend
      on rapid sensing of the infection by the innate immune response prior to
      deployment of viral immunosubversive functions. Control of HCMV dissemination
      could be ensured by apoptosis of cells immediately following infection. In the
      present report, it is demonstrated that changes in the ratio of c-FLIP to FLICE
      contributed to early sensitivity of HCMV-infected MRC5 fibroblasts to tumour
      necrosis factor alpha (TNF-alpha), providing an innate response to infection.
      Dendritic cells (DCs) co-cultured with HCMV-infected MRC5 cells acquired the
      ability to secrete TNF-alpha in an amount sufficient to kill infected
      fibroblasts. Blockage of TNF-alpha binding to its receptor on MRC5 cells with
      soluble TNF-R reduced the number of dead, HCMV-infected fibroblasts ingested by
      DCs, thus highlighting the impact of the apoptotic state of infected cells for
      efficient loading of DCs. Those DCs loaded with antigens available early in
      infection, such as input virion-associated pp65, could then engage antigen
      processing for cross-presentation to specific CD8(+) T cells. Cross-presentation
      was impaired when MRC5 cells were treated with the pan-caspase inhibitor ZVAD
      before co-culture with DCs. Altogether, our data suggest that the innate killing
      capacity of DCs at the early stage of infection plays a role in the activation of
      anti-HCMV CD8(+) T cells.

PMID- 18089732
TI  - Human herpesvirus 6B induces phosphorylation of p53 in its regulatory domain by a
      CK2- and p38-independent pathway.
AB  - Here, we demonstrate that human herpesvirus 6B (HHV-6B) infection upregulates the
      tumour suppressor p53 and induces phosphorylation of p53 at Ser392.
      Interestingly, phosphorylation at the equivalent site has previously been shown
      to correlate with p53 tumour suppression in murine models. Although the
      signalling pathways leading to Ser392 phosphorylation are poorly understood, they
      seem to include casein kinase 2 (CK2), double-stranded RNA-activated protein
      kinase (PKR), p38 or cyclin-dependent kinase 9 (Cdk9). By using column
      chromatography and in vitro kinase assays, CK2 and p38, but not PKR or Cdk9,
      eluted in column fractions that phosphorylated p53 at Ser392. However, treatment
      of cells with neither the CK2 and Cdk9 inhibitor 5,6-dichloro-1-beta-d
      ribofuranosylbenzimidazole (DRB) nor p38 kinase inhibitors reduced HHV-6B-induced
      Ser392 phosphorylation significantly. Knockdown of the CK2beta subunit or
      p38alpha by small interfering RNA had no effect on HHV-6B-induced phosphorylation
      of p53 at Ser392. Thus, HHV-6B induces p53 Ser392 phosphorylation by an atypical
      pathway independent of CK2 and p38 kinases, whereas mitogen-activated protein
      (MAP) kinase signalling pathways are involved in viral replication.

PMID- 18089734
TI  - Human herpesvirus 6B U19 protein is a PML-regulated transcriptional activator
      that localizes to nuclear foci in a PML-independent manner.
AB  - Human herpesvirus 6B (HHV-6B) contains an IE-B domain spanning open reading
      frames U16/17-U19, based on homology with human cytomegalovirus. Here, the
      protein product, U19, of the HHV-6B U19 gene is identified as a 47 kDa
      transcriptional activator. HHV-6B infection or overexpression of U19
      transactivated the RANTES promoter. Mutational analysis of the promoter indicated
      that transactivation was not critically dependent on the promoter sites CRE, NF
      kappaB, ISRE or NF-IL6. ND10 are nuclear substructures that are involved in
      several cellular regulatory pathways, including those controlling gene
      expression. HHV-6B infection resulted in a reduced number of ND10 structures, but
      with a concomitantly increased level of promyelocytic leukaemia (PML) protein
      expression and mRNA induction. The U19 protein co-located to ND10 with PML and
      heterochromatin protein 1 (HP1), but whilst PML formed a ring structure, U19 also
      localized to the centre of ND10. Knockdown of PML by small interfering RNA did
      not prevent U19 localization to ND10-like foci, but instead led to a fourfold
      increase in U19-induced transcription from the RANTES promoter. Generation of
      four truncated U19 proteins indicated that the N-terminal portion of the protein
      contains a sequence responsible for nuclear localization; a domain in the N
      terminal half of U19 is responsible for its ND10 localization, whereas the C
      terminal portion contains the transactivation domain. None of the truncated
      proteins retained full transactivating ability on the RANTES promoter. Thus, U19
      is a transcriptional activator that co-localizes with PML and localizes to ND10
      like foci independently of PML, yet is regulated negatively by PML or its
      associated proteins.

PMID- 18089733
TI  - Functional analysis of human cytomegalovirus pUS28 mutants in infected cells.
AB  - The human cytomegalovirus (HCMV)-encoded viral G protein-coupled receptor pUS28
      contributes to an array of biological effects, including cell migration and
      proliferation. Using FIX-BAC (bacterial artificial chromosome, derived from the
      HCMV clinical isolate VR1814) and lambda red recombination techniques, we
      generated HCMV recombinants expressing amino-terminally FLAG-tagged versions of
      wild-type pUS28 (FLAG-US28/WT), G-protein coupling deficient pUS28 (FLAG
      US28/R129A) and chemokine-binding domain deficient pUS28 (FLAG-US28/DeltaN).
      Infection with the FLAG-US28/R129A virus failed to induce inositol phosphate
      accumulation, indicating that G-protein coupling is essential for pUS28
      signalling to phospholipase C-beta (PLC-beta) during HCMV infection. The FLAG
      US28/DeltaN virus induced about 80 % of the level of PLC-beta signalling induced
      by the FLAG-US28/WT virus, demonstrating that the N-terminal chemokine-binding
      domain is not required for pUS28-induced PLC-beta signalling in infected cells.
      The data presented here are the first to describe the functional analyses of
      several key pUS28 mutants in HCMV-infected cells. Elucidating the mechanisms by
      which pUS28 signals during infection will provide important insights into HCMV
      pathogenesis.

PMID- 18089735
TI  - Reactivity pattern of 92 monoclonal antibodies with 15 human papillomavirus
      types.
AB  - Most anti-human papillomavirus (HPV) capsid antibody assays are based on virus
      like particles (VLP). We evaluated glutathione S-transferase (GST)-L1 fusion
      proteins as ELISA antigens for determining type specificity and cross-reactivity
      of 92 VLP-specific monoclonal antibodies (mAb) generated against nine mucosal
      alpha papillomavirus types of species 7, 9 and 10. The antibody panel included 25
      new mAb, and 24 previously published mAb are further characterized. We determined
      the cross-reactivity patterns with 15 different HPV types representing 6 species
      (alpha1, 2, 4, 7, 9 and 10) and neutralization and cross-neutralization
      properties with HPV types 6, 11, 16, 18 and 45. Eighty-nine (97 %) of the
      antibodies including 34, 71 and 14 recognizing neutralizing, conformational and
      linear epitopes, respectively, reacted with the GST-L1 protein of the HPV type
      used as immunogen, with log titres ranging from 2.0 to 7.3. Of these 89
      antibodies, 52 % were monotypic, 20 % showed intra-species and 28 % inter-species
      cross-reactivity. Log neutralization titres to the immunogen HPV ranged from 1.7
      to 5.6. A single cross-neutralizing mAb (H6.L12) was found. ELISA titres were
      always higher than neutralization titres. All neutralizing epitopes were
      conformational and mostly type-specific. Our data show that bacterially
      expressed, affinity-purified GST-L1 fusion proteins display a broad variety of
      epitopes and thus are well suited for detection of HPV antibodies. Cross
      reactivity is associated with linear as well as conformational epitopes.
      Distantly related mucosal and skin alpha papillomaviruses share some
      conformational epitopes and the phylogenetic L1-based species definition may not
      define a serological unit since no species-specific epitope was found.

PMID- 18089736
TI  - Molecular characterization of the first polyomavirus from a New World primate:
      squirrel monkey polyomavirus.
AB  - DNA samples from a variety of New World monkeys were screened by using a broad
      spectrum PCR targeting the VP1 gene of polyomaviruses. This resulted in the
      characterization of the first polyomavirus from a New World primate. This virus
      naturally infects squirrel monkeys (Saimiri sp.) and is provisionally named
      squirrel monkey polyomavirus (SquiPyV). The complete genome of SquiPyV is 5,075
      bp in length, and encodes the small T and large T antigens and the three
      structural proteins VP1, VP2 and VP3. Interestingly, the late region also encodes
      a putative agnoprotein, a feature that it shares with other polyomaviruses from
      humans, baboons and African green monkeys. Comparison with other polyomaviruses
      revealed limited sequence similarity to any other polyomavirus, and phylogenetic
      analysis of the VP1 gene confirmed its uniqueness.

PMID- 18089737
TI  - Immunotherapy of equine sarcoid: dose-escalation trial for the use of chimeric
      papillomavirus-like particles.
AB  - Equine sarcoids are fibrosarcoma-like skin tumours with a prevalence of
      approximately 1-2 %. Strong evidence exists for a causative role of bovine
      papillomavirus (BPV) type 1 or type 2 in the development of sarcoids. No
      effective treatment of equine sarcoid is available and after surgical excision
      relapse of the tumours is very frequent. We developed chimeric virus-like
      particles (CVLPs) of BPV 1 L1-E7 for the immunotherapy of equine sarcoid. In a
      phase I clinical trial 12 horses suffering from equine sarcoid with an average
      number of more than 22 tumours per animal were vaccinated in a dose-escalation
      setting. The animals were followed-up for 63 days, eight of the twelve horses
      were followed-up for more than a year and side-effects, humoral immune responses
      and tumour appearance were recorded. BPV DNA was detected in tumours of 11 cases.
      CVLPs were well tolerated in all dose groups, a robust anti-L1 antibody response
      was induced in all but one of the horses. Anti-E7 antibodies were detected in
      five of the 12 animals at low titres. Two animals showed a clear improvement of
      the clinical status after treatment, i.e. the number of the tumours per horse was
      reduced. In another horse regression of five sarcoids was observed; three of them
      relapsed during the study. Two animals showed tumour regression as well as growth
      of new sarcoids. In two horses the clinical status remained unchanged, in another
      two horses growth of existing tumours or growth of additional tumours was
      observed. The remaining three animals showed simultaneously regression and growth
      of existing tumours. Neither the humoral immune responses nor the observed
      effects on the tumours was correlated with the dose group.

PMID- 18089738
TI  - Vaccination of sarcoid-bearing donkeys with chimeric virus-like particles of
      bovine papillomavirus type 1.
AB  - Equine sarcoids are fibroblastic skin tumours affecting equids worldwide. While
      the pathogenesis is not entirely understood, infection with bovine papillomavirus
      (BPV) type 1 (and less commonly type 2) has been implicated as a major factor in
      the disease process. Sarcoids very seldom regress and in fact often recrudesce
      following therapy. Nothing is known about the immune response of the equine host
      to BPV. Given that the viral genes are expressed in sarcoids, it is reasonable to
      assume that vaccination of animals against the expressed viral proteins would
      lead to the induction of an immune response against the antigens and possible
      tumour rejection. To this end we vaccinated sarcoid-bearing donkeys in a placebo
      controlled trial using chimeric virus-like particles (CVLPs) comprising BPV-1 L1
      and E7 proteins. The results show a tendency towards enhanced tumour regression
      and reduced progression in the vaccinated group compared to control animals.
      Although promising, further studies are required with larger animal groups to
      definitely conclude that vaccination with CVLPs is a potential therapy for the
      induction of sarcoid regression.

PMID- 18089739
TI  - Genomic and phylogenetic analysis of two novel bovine papillomaviruses, BPV-9 and
      BPV-10.
AB  - Eight bovine papillomavirus (BPV) types, BPV-1-8, have been classified, based on
      genome nucleotide sequence similarities, in the genera Deltapapillomavirus (BPV-1
      and -2), Epsilonpapillomavirus (BPV-5 and -8), Xipapillomavirus (BPV-3, -4 and 
      6) and an unassigned genus (BPV-7). We report here the complete genome sequence
      of two new BPV types isolated from separate epithelial squamous papilloma lesions
      on cattle teats. The genomes are 7,303 and 7,399 bp in length, respectively, and
      both have genetic organization and consensus motifs typical of papillomaviruses.
      A neighbour-joining phylogenetic tree revealed that both viruses cluster with BPV
      3, -4 and -6. Nucleotide sequence identities of the BPV L1 major capsid protein
      of these two new BPVs with BPV-3, their closest relative, are 74.2 and 71.2 %,
      respectively. These results suggest that both viruses are new BPV types in the
      genus Xipapillomavirus, and they are designated BPV-9 and BPV-10.

PMID- 18089740
TI  - Simultaneous persistence of multiple genome variants of human parvovirus B19.
AB  - The species human parvovirus B19 (B19V) can be divided into three genotypes. In
      this study, we addressed the question as to whether infection of an individual is
      restricted to one genotype. As viral DNA is detectable in tissue for long times
      after acute infection, we examined 87 liver specimens from adults for the
      presence of B19V DNA. Fifty-nine samples were found to be positive, 32 of them
      for genotype 1, 27 for genotype 2 and four for genotype 3. In four samples, DNA
      of two genotypes was detected; samples from three individuals were positive for
      genotypes 1 and 2 and a sample from one individual was positive for genotypes 1
      and 3. Surprisingly, significant sequence heterogeneity was observed at
      approximately 1 % of the nucleotides of the genotype 1 genomes from individuals
      with double genotype 1 and 2 infection. Controls using different enzymes for
      genome amplification and dilutions of the template verified that nucleotide
      heterogeneity was due to the presence of three or more genome variants of
      genotype 1. In summary, the evidence shows that individuals can be infected with
      two different genotypes, and B19V DNA can persist as a population of different
      genomes. The results may have implications for the understanding of the antiviral
      immune response and the development of vaccines against B19V.

PMID- 18089741
TI  - Antigenic differences among porcine circovirus type 2 strains, as demonstrated by
      the use of monoclonal antibodies.
AB  - This study examined whether antigenic differences among porcine circovirus type 2
      (PCV-2) strains could be detected using monoclonal antibodies (mAbs). A
      subtractive immunization protocol was used for the genotype 2 post-weaning
      multisystemic wasting syndrome (PMWS)-associated PCV-2 strain Stoon-1,010.
      Sixteen stable hybridomas that produced mAbs with an immunoperoxidase monolayer
      assay (IPMA) titre of 1,000 or more to Stoon-1,010 were obtained. Staining of
      recombinant PCV-2 virus-like particles demonstrated that all mAbs were directed
      against the PCV-2 capsid protein. Cross-reactivity of mAbs was tested by IPMA and
      neutralization assay for genotype 1 strains 48,285, 1,206, VC2,002 and 1,147, and
      genotype 2 strains 1,121 and 1,103. Eleven mAbs (9C3, 16G12, 21C12, 38C1, 43E10,
      55B1, 63H3, 70A7, 94H8, 103H7 and 114C8) recognized all strains in the IPMA and
      demonstrated neutralization of Stoon-1,010, 48,285, 1,206 and 1,103, but not
      VC2,002, 1,147 and 1,121. mAbs 31D5, 48B5, 59C6 and 108E8 did not react with
      genotype 1 strains or had a reduced affinity compared with genotype 2 strains in
      the IPMA and neutralization assay. mAb 13H4 reacted in the IPMA with PMWS
      associated strains Stoon-1,010, 48,285, 1,206 and VC2,002, and the porcine
      dermatitis and nephropathy syndrome-associated strain 1,147, but not with
      reproductive failure-associated strains 1,121 and 1,103. mAb 13H4 did not
      neutralize any of the tested strains. It was concluded that, despite the high
      amino acid identity of the capsid protein (>or=91 %), antigenic differences at
      the capsid protein level are present among PCV-2 strains with a different genetic
      and clinical background.

PMID- 18089742
TI  - A silkworm baculovirus model for assessing the therapeutic effects of antiviral
      compounds: characterization and application to the isolation of antivirals from
      traditional medicines.
AB  - Ganciclovir, foscarnet, vidarabine and ribavirin, which are used to treat viral
      infections in humans, inhibited the proliferation of a baculovirus (Bombyx mori
      nucleopolyhedrovirus) in BmN4 cells, a cultured silkworm cell line. These
      antiviral agents inhibited the proliferation of baculovirus in silkworm body
      fluid and had therapeutic effects. Using the silkworm infection model, the
      antiviral activity of Kampo medicines was screened and it was found that cinnamon
      bark, a component of the traditional Japanese medicine Mao-to, had a therapeutic
      effect. Based on the therapeutic activity, the antiviral substance was purified.
      Nuclear magnetic resonance analysis of the purified fraction revealed that the
      antiviral activity was due to cinnzeylanine, which has previously been isolated
      from Cinnamomum zeylanicum. Cinnzeylanine inhibits the proliferation of herpes
      simplex virus type 1 in Vero cells. These results suggest that the silkworm
      baculovirus infection model is useful for screening antiviral agents that are
      effective for treating humans infected with DNA viruses.

PMID- 18089743
TI  - Isolation and characterization of the full coding sequence of a novel densovirus
      from the mosquito Culex pipiens pallens.
AB  - During an investigation of arboviruses in China, a novel densovirus (DNV) was
      isolated from the adult female Culex pipiens pallens. The virus, designated Culex
      pipiens pallens densovirus (CppDNV), caused cytopathic effect in C6/36 cells. The
      virus particles were icosahedral, non-enveloped and had a mean diameter of 24 nm.
      The complete coding region of CppDNV was found to be 3335 nt and it contained
      three open reading frames (ORFs). CppDNV shares 82-93 % identical nucleotides
      with isolates of the Aedes albopictus densovirus [isolates AalDNV-1, AalDNV-2
      (C6/36 DNV) and AalDNV-3], Aedes aegypti densovirus (AaeDNV) and Haemagogus
      equines densovirus (HeDNV). The nucleotide sequence identity among CppDNV
      isolates exceeds 98 %. Phylogenetic trees based on non-structural (NS1 and NS2)
      and capsid (VP) genes show that CppDNV clustered with the species AaeDNV and
      represents a novel variant of this species within the genus Brevidensovirus.

PMID- 18089744
TI  - Construction and application of chimeric virus-like particles of tick-borne
      encephalitis virus and mosquito-borne Japanese encephalitis virus.
AB  - We have previously reported a system for packaging tick-borne encephalitis (TBE)
      virus subgenomic replicon RNAs into single-round infectious virus-like particles
      (VLPs) by using in trans expression of viral C/prM/E structural proteins. In this
      study, the trans-packaging system was applied to the generation of chimeric VLPs
      with mosquito-borne Japanese encephalitis (JE) virus. Although trans-expression
      of TBE virus C and JE virus prM/E proteins resulted in the secretion of VLPs, the
      expression of JE virus C/prM/E proteins did not lead to the secretion of VLPs,
      suggesting that homologous interaction between C and non-structural proteins or
      the genomic RNA is important for efficient assembly of infectious particles.
      Neutralization testing showed that the antigenic characteristics of the VLPs were
      similar to those of the native virus. Furthermore, the infectivities of the TBE
      virus- and JE virus-enveloped VLPs for the ISE6 tick cell line and C6/36 mosquito
      cell line were investigated. The VLPs were able to enter only those cells that
      were derived from the natural vectors for the respective viruses. TBE virus
      replicon RNA packaged in VLPs produced TBE virus non-structural proteins in tick
      cells, but could neither replicate nor produce viral proteins in mosquito cells.
      These findings indicate the importance of specific cellular factors for virus
      entry and replication during flavivirus infection of arthropods. These results
      demonstrate that chimeric VLPs are useful tools for the study of viral genome
      packaging and cellular factors involved in vector specificity, with the
      additional safety aspect that these chimeric VLPs can be used instead of full
      length chimeric viruses.

PMID- 18089745
TI  - Seven nucleotide changes characteristic of the hepatitis C virus genotype 3 5'
      untranslated region: correlation with reduced in vitro replication.
AB  - Computer analysis of 158 hepatitis C virus (HCV) 5' untranslated region (5' UTR)
      sequences from the six genotypes showed that the 5' UTR from genotype 3 displays
      seven specific non-contiguous nucleotide changes, at positions 8, 13, 14, 70, 97,
      203 and 224. The purpose of this study was to investigate the impact of these
      changes on translation and replication activities. Indeed, these modifications
      could alter both the internal ribosome entry site (IRES) present in the 5' UTR of
      the plus-strand RNA and the 3' end of the minus strand involved in the initiation
      of plus-strand RNA synthesis. We found that the genotype 3-specific nucleotide
      changes do not modify the in vitro or ex vivo translation activity of the
      corresponding IRES, in comparison with that of genotype 1. In contrast, in vitro
      replication from the minus-strand RNA is eight times less efficient for genotype
      3 than for genotype 1 RNA, suggesting the involvement of some nucleotide changes
      in the reduction of RNA synthesis. Nucleotides 13, 14 and 224 were found to be
      responsible for this effect. Moreover, a reduced replicative activity was
      confirmed ex vivo for genotype 3, but to a lesser extent than that observed in
      vitro, using an RNA minigenome.

PMID- 18089746
TI  - Differences in the expression of the hepatitis C virus core+1 open reading frame
      between a nuclear and a cytoplasmic expression system.
AB  - The hepatitis C virus (HCV) genome possesses an open reading frame (ORF)
      overlapping the core gene at +1 nucleotide (core+1 ORF). Initial in vitro studies
      suggested that the core+1 ORF is translated by a ribosomal -2/+1 frameshift
      mechanism during elongation of the viral polyprotein. Recent studies, however,
      based on transfection of mammalian cells with reporter constructs have shown that
      translation of the core+1 ORF is mediated from internal core+1 codons. To resolve
      the apparent discrepancies associated with the mechanism of core+1 translation,
      we examined the expression of the HCV-1 and HCV-1a (H) core+1 ORF in a
      cytoplasmic transcription system based on Huh-7/T7 cells that constitutively
      synthesize the T7 RNA polymerase in comparison to that in Huh-7 cells. We showed
      that the efficiency of both the -2/+1 and -1/+2 frameshift events operating at
      the HCV-1 core codons 8-11 is significantly enhanced in the Huh-7/T7 cytoplasmic
      transcription system and is dependent on the presence of the consecutive adenine
      (A) residues within core codons 8-11. In contrast, internal translation
      initiation at core+1 codons 85/87 occurs in both the nuclear and cytoplasmic
      transcription systems and is not repressed by the ribosomal frameshifting event.
      Finally, although core+1 codons 85/87 is the most efficient site for internal
      initiation of core+1 translation, it may not be unique, as additional internal
      core+1 codon(s) appear to drive translation at low levels.

PMID- 18089747
TI  - Persistence of foot-and-mouth disease virus in cell culture revisited:
      implications for contingency in evolution.
AB  - If we could rewind the tape of evolution and play it again, would it turn out to
      be similar to or different from what we know? Obviously, this key question can
      only be addressed by fragmentary experimental approaches. Twenty-two years ago,
      we described the establishment of BHK-21 cells persistently infected with foot
      and-mouth disease virus (FMDV), a system that displayed as its major biological
      feature a coevolution of the cells and the resident virus in the course of
      persistence. Now we report the establishment of two persistently infected cell
      lines in parallel, starting with the same clones of FMDV and BHK-21 cells used 22
      years ago. We have asked whether the evolution of the two newly established cell
      lines and of the earlier cell line would be similar or different. The main
      conclusions of the study are: (i) the basic behaviour characterized by virus-cell
      coevolution is similar in the three carrier cell lines, despite differences in
      some genetic alterations of FMDV; (ii) a strikingly parallel behaviour has been
      observed with the two newly established cell lines passaged in parallel,
      unveiling a deterministic virus behaviour during persistence; and (iii) selective
      RT-PCR amplifications have detected imbalances in the proportion of positive-
      versus negative-strand viral RNA, mediated by both viral and cellular factors.
      The results confirm coevolution of cells and virus as a major and reproducible
      feature of FMDV persistence in cell culture, and suggest that rapidly evolving
      viruses may constitute adequate test systems to probe the influence of historical
      contingency on evolutionary events.

PMID- 18089748
TI  - Putative receptor-binding sites of hepatitis E virus.
AB  - A truncated structural protein of hepatitis E virus (HEV), p239, occurs as 23 nm
      particles consisting of partial homodimers. As the latter resemble the HEV
      capsomere structurally and antigenically, it was postulated that the recombinant
      protein may serve as a probe for the HEV receptor. This hypothesis was supported
      by findings that purified p239 bound and penetrated different cell lines that are
      susceptible to HEV, and inhibited HEV infection of these cells. The binding was
      blocked by four of six monoclonal antibodies (mAbs) reactive against the dimeric
      domain of p239, and by two of three mAbs reactive against its monomeric domain,
      suggesting that binding may involve a portion of each domain. Mutation affecting
      the monomeric domain had no effect on binding or capacity to block HEV infection,
      whereas that affecting the dimeric domain diminished binding of the mutant
      peptide markedly and abrogated its capacity to block HEV infection. These results
      suggest that HEV infection might involve distinct receptor-binding sites.

PMID- 18089749
TI  - Intranasal immunization of mice with a formalin-inactivated bovine respiratory
      syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and
      polyphosphazenes results in enhanced protection.
AB  - As respiratory syncytial virus (RSV) targets the mucosal surfaces of the
      respiratory tract, induction of both systemic and mucosal immunity will be
      critical for optimal protection. In this study, the ability of an intranasally
      delivered, formalin-inactivated bovine RSV (FI-BRSV) vaccine co-formulated with
      CpG oligodeoxynucleotides (ODN) and polyphosphazenes (PP) to induce systemic and
      mucosal immunity, as well as protection from BRSV challenge, was evaluated.
      Intranasal immunization of mice with FI-BRSV formulated with CpG ODN and PP
      resulted in both humoral and cell-mediated immunity, characterized by enhanced
      production of BRSV-specific serum IgG, as well as increased gamma interferon and
      decreased interleukin-5 production by in vitro-restimulated splenocytes. These
      mice also developed mucosal immune responses, as was evident from increased
      production of BRSV-specific IgG and IgA in lung-fragment cultures. Indeed, the
      increases in serum and mucosal IgG, and in particular mucosal IgA and virus
      neutralizing antibodies, were the most critical differences observed between FI
      BRSV formulated with both CpG ODN and PP in comparison to formulations with CpG
      ODN, non-CpG ODN or PP individually. Finally, FI-BRSV/CpG/PP was the only
      formulation that resulted in a significant reduction in viral replication upon
      BRSV challenge. Co-formulation of CpG ODN and PP is a promising new vaccine
      platform technology that may have applications in mucosal immunization in humans.

PMID- 18089751
TI  - Novel reassortant of swine influenza H1N2 virus in Germany.
AB  - European porcine H1N2 influenza viruses arose after multiple reassortment steps
      involving a porcine influenza virus with avian-influenza-like internal segments
      and human H1N1 and H3N2 viruses in 1994. In Germany, H1N2 swine influenza viruses
      first appeared in 2000. Two German H1N2 swine influenza virus strains isolated
      from pigs with clinical symptoms of influenza are described. They were
      characterized by the neutralization test, haemagglutination inhibition (HI) test
      and complete sequencing of the viral genomes. The data demonstrate that these
      viruses represent a novel H1N2 reassortant. The viruses showed limited
      neutralization by sera raised against heterologous A/sw/Bakum/1,832/00-like H1N2
      viruses. Sera pools from recovered pigs showed a considerably lower HI reaction,
      indicative of diagnostic difficulties in using the HI test to detect these
      viruses with A/sw/Bakum/1,832/00-like H1N2 antigens. Genome sequencing revealed
      the novel combination of the human-like HAH1 gene of European porcine H1N2
      influenza viruses and the NAN2 gene of European porcine H3N2 viruses.

PMID- 18089750
TI  - Induction of type I interferons and interferon-inducible Mx genes during
      respiratory syncytial virus infection and reinfection in cotton rats.
AB  - Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis in young
      children. In general, RSV is considered to be a poor inducer of type I
      (alpha/beta) interferons (IFNs). Measurement of active type I IFN production
      during infection in vivo is demanding, as multiple IFN subtypes with overlapping
      activities are produced. In contrast, Mx gene expression, which is tightly
      regulated by type I IFN expression, is easily determined. This study therefore
      measured Mx expression as a reliable surrogate marker of type I IFN activity
      during RSV infection in vivo in a cotton rat model. It was shown that expression
      of Mx genes was dramatically augmented in the lungs of infected animals in a dose
      and virus strain-dependent manner. The expression of Mx genes in the lungs was
      paralleled by their induction in the nose and spleen, although in spleen no
      simultaneous virus gene expression was detected. Reinfection of RSV-immune
      animals leads to abortive virus replication in the lungs. Thus, type I IFN and Mx
      gene expression was triggered in reinfected animals, even though virus could not
      be isolated from their lungs. Furthermore, it was demonstrated that immunity to
      RSV wanes with time. Virus replication and Mx gene expression became more
      prominent with increasing intervals between primary infection and reinfection.
      These results highlight the role of type I IFN in modulation of the immune
      response to RSV.

PMID- 18089752
TI  - CD134 and CXCR4 expression corresponds to feline immunodeficiency virus infection
      of lymphocytes, macrophages and dendritic cells.
AB  - The lymphotropic lentiviruses feline immunodeficiency virus (FIV) and human
      immunodeficiency virus (HIV) enter cells by sequential interaction with primary
      receptors CD134 or CD4, respectively, and subsequently with chemokine receptors.
      The host-cell range for FIV is broader than that for HIV, but whether this is a
      function of receptor expression is unknown. Lack of reagents specific to feline
      molecules has limited detection and analysis of receptors and their interaction
      with viral components. Here, the expression of CD134 and CXCR4 on feline T and B
      lymphocytes, dendritic cells (DCs) and macrophages was examined and the kinetics
      of FIV replication were assessed. Quantification of CD134 mRNA by real-time PCR
      indicated expression in all leukocytes, with significantly more transcripts in
      CD4(+) lymphocytes than in other leukocytes. Antibodies against human CD134 bound
      inconsistently to feline leukocytes. CXCR4 was detected with antibody clone 12G5
      on the surface of monocyte-derived cells only, but gene transcripts were present
      in all cells, with the highest copy number in lymphocytes. CXCR4 expression
      decreased and CD134 expression increased with cell activation in lymphocytes. A
      subtype B biological isolate of FIV infected DCs, macrophages and lymphocytes,
      with the highest replication in CD4(+) lymphocytes, whilst cloned FIV P14
      infected all cells, but replicated less efficiently. Although viral replication
      was lower in DCs and macrophages than in lymphocytes, DCs expressed specific
      receptors and were infected productively with FIV, as indicated by viral
      ultrastructure and DNA detection. These results may implicate altered function of
      DCs in the induction of specific immunity against FIV.

PMID- 18089754
TI  - Mechanisms underlying glycosylation-mediated loss of ecotropic receptor function
      in murine MDTF cells and implications for receptor evolution.
AB  - A Mus dunni tail fibroblast (MDTF) cell line is highly resistant to infection by
      ecotropic Moloney murine leukemia virus (Mo-MLV). The cationic amino acid
      transporter type 1 (CAT1) paralogues of murine NIH 3T3 and MDTF cells (mCAT1 and
      dCAT1, respectively) contain two conserved N-linked glycosylation sites in the
      third extracellular loop (ECL3, the putative Mo-MLV binding site). Glycosylation
      of dCAT1 inhibits Mo-MLV infection, but that of mCAT1 does not. Compared with
      mCAT1, dCAT1 possesses an Ile-to-Val substitution at position 214 and a Gly
      insertion at position 236 in the ECL3. To determine the residues responsible for
      the loss of dCAT1 receptor function, mutants of mCAT1 were constructed. The
      mCAT1/insG receptor (with a Gly residue inserted at mCAT1 position 236) had
      greatly reduced Mo-MLV receptor function compared with mCAT1. Treatment of
      mCAT1/insG-expressing cells with tunicamycin, an N-linked glycosylation
      inhibitor, increased the transduction titre. In addition, the reduced
      susceptibility to Mo-MLV observed with mCAT1/insG-expressing cells correlated
      with impaired binding of Mo-MLV. These results show that a single amino acid
      insertion confers mCAT1 receptor properties on dCAT1 and provide an important
      insight into the co-evolution of virus-host interactions.

PMID- 18089753
TI  - N-Myristoyltransferase isozymes exhibit differential specificity for human
      immunodeficiency virus type 1 Gag and Nef.
AB  - Myristoylation of the human immunodeficiency virus type 1 (HIV-1) proteins Gag
      and Nef by N-myristoyltransferase (NMT) is a key process in retroviral
      replication and virulence, yet remains incompletely characterized. Therefore, the
      roles of the two isozymes, NMT1 and NMT2, in myristoylating Gag and Nef were
      examined using biochemical and molecular approaches. Fluorescently labelled
      peptides corresponding to the N terminus of HIV-1 Gag or Nef were myristoylated
      by recombinant human NMT1 and NMT2. Kinetic analyses indicated that NMT1 and NMT2
      had 30- and 130-fold lower K(m )values for Nef than Gag, respectively. Values for
      K(cat) indicated that, once Gag or Nef binds to the enzyme, myristoylation by
      NMT1 and NMT2 proceeds at comparable rates. Furthermore, the catalytic
      efficiencies for the processing of Gag by NMT1 and NMT2 were equivalent. In
      contrast, NMT2 had approximately 5-fold higher catalytic efficiency for the
      myristoylation of Nef than NMT1. Competition experiments confirmed that the Nef
      peptide acts as a competitive inhibitor for the myristoylation of Gag.
      Experiments using full-length recombinant Nef protein also indicated a lower K(m)
      for Nef myristoylation by NMT2 than NMT1. Small interfering RNAs were used to
      selectively deplete NMT1 and/or NMT2 from HEK293T cells expressing a recombinant
      Nef-sgGFP fusion protein. Depletion of NMT1 had minimal effect on the
      intracellular distribution of Nef-sgGFP, whereas depletion of NMT2 altered
      distribution to a diffuse, widespread pattern, mimicking that of a myristoylation
      deficient mutant of Nef-sgGFP. Together, these findings indicate that Nef is
      preferentially myristoylated by NMT2, suggesting that selective inhibition of
      NMT2 may provide a novel means of blocking HIV virulence.

PMID- 18089755
TI  - Pathogenicity of a naturally occurring recombinant DNA satellite associated with
      tomato yellow leaf curl China virus.
AB  - Recombinant DNA beta molecules (RecDNA-Abeta) comprising parts of DNA A and DNA
      beta associated with tomato yellow leaf curl China virus (TYLCCNV) have been
      identified in naturally infected tobacco plants. Several examples of the
      recombinant DNA have been cloned and characterized by sequence analysis. All are
      approximately half the size of TYLCCNV genomic DNA, and all contain the betaC1
      gene and the A-rich region from TYLCCNV DNA beta as well as intergenic region
      sequences and the 5' terminus of the AC1 gene from TYLCCNV DNA A. RecDNA-Abeta
      was detected by PCR in five of 25 TYLCCNV isolates. Co-inoculation of TYLCCNV DNA
      A and RecDNA-Abeta induced symptoms indistinguishable from those induced by
      TYLCCNV DNA A and DNA beta in Nicotiana benthamiana, Nicotiana glutinosa, Solanum
      lycopersicum and Petunia hybrida plants, and Southern blot hybridization results
      showed that RecDNA-Abeta could replicate stably in N. benthamiana plants.

PMID- 18089756
TI  - Molecular characterization of begomoviruses and DNA satellites from Vietnam:
      additional evidence that the New World geminiviruses were present in the Old
      World prior to continental separation.
AB  - Sixteen viruses, belonging to 16 species of begomovirus, that infect crops and
      weeds in Vietnam were identified. Sequence analysis of the complete genomes
      showed that nine of the viruses (six monopartite and three bipartite) belong to
      novel species and five of them were identified in Vietnam for the first time.
      Additionally, eight DNA-beta and three nanovirus-like DNA-1 molecules were also
      found associated with some of the monopartite viruses. Five of the DNA-beta
      molecules were novel. Importantly, a second bipartite begomovirus, Corchorus
      golden mosaic virus, shared several features with the previously characterized
      virus Corchorus yellow vein virus and with other bipartite begomoviruses from the
      New World, supporting the hypothesis that New World-like viruses were present in
      the Old World. This, together with a high degree of virus diversity that included
      putative recombinant viruses, satellite molecules and viruses with previously
      undescribed variability in the putative stem-loop sequences, suggested that South
      East Asia, and Vietnam in particular, is one of the origins of begomovirus
      diversity.

PMID- 18089757
TI  - Evaluation of potential risks associated with recombination in transgenic plants
      expressing viral sequences.
AB  - Virus-resistant transgenic plants have been created primarily through the
      expression of viral sequences. It has been hypothesized that recombination
      between the viral transgene mRNA and the RNA of an infecting virus could generate
      novel viruses. As mRNA/viral RNA recombination can occur in virus-resistant
      transgenic plants, the key to testing this risk hypothesis is to compare the
      populations of recombinant viruses generated in transgenic and non-transgenic
      plants. This has been done with two cucumoviral systems, involving either two
      strains of cucumber mosaic virus (CMV), or CMV and the related tomato aspermy
      virus (TAV). Although the distribution of the sites of recombination in the
      CMV/CMV and TAV/CMV systems was quite different, equivalent populations of
      recombinant viruses were observed in both cases. These results constitute the
      first comparison of the populations of recombinants in transgenic and non
      transgenic plants, and suggest that there is little risk of emergence of
      recombinant viruses in these plants, other than those that could emerge in non
      transgenic plants.

PMID- 18089758
TI  - The NS3 protein of rice hoja blanca virus suppresses RNA silencing in mammalian
      cells.
AB  - The NS3 protein of the tenuivirus rice hoja blanca virus (RHBV) has previously
      been shown to represent the viral RNA interference (RNAi) suppressor and is
      active in both plant and insect cells by binding short interfering RNAs (siRNAs)
      in vitro. Using a firefly luciferase-based silencing assay it is described here
      that NS3 is also active in mammalian cells. This activity is independent of the
      inducer molecule used. Using either synthetic siRNAs or a short hairpin RNA
      construct, NS3 was able to significantly suppress the RNAi-mediated silencing of
      luciferase expression in both monkey (Vero) and human (HEK293) cells. These
      results support the proposed mode of action of NS3 to act by sequestering siRNAs,
      the key molecules of the RNAi pathway conserved in all eukaryotes. The possible
      applications of this protein in modulating RNAi and investigating the proposed
      antiviral RNAi response in mammalian cell systems are discussed.

PMID- 18089759
TI  - A cell line infectible by prion strains from different species.
AB  - It has been shown previously that ovine prion protein (PrP(C)) renders rabbit
      epithelial RK13 cells permissive to the multiplication of ovine prions, thus
      providing evidence that species barriers can be crossed in cultured cells through
      the expression of a relevant PrP(C). The present study significantly extended
      this observation by showing that mouse and bank vole prions can be propagated in
      RK13 cells that express the corresponding PrP(C). Importantly, the respective
      molecular patterns of abnormal PrP (PrP(res)) and, where examined, the
      neuropathological features of the infecting strains appeared to be maintained
      during the propagation in cell culture. These findings indicate that RK13 cells
      can be genetically engineered to replicate prion strains faithfully from
      different species. Such an approach may facilitate investigations of the
      molecular basis of strain identity and prion diversity.

PMID- 18089760
TI  - Decontamination of surgical instruments from prions. II. In vivo findings with a
      model system for testing the removal of scrapie infectivity from steel surfaces.
AB  - The unusual resistance of agents causing transmissible spongiform
      encephalopathies (TSEs) to chemical or thermal inactivation requires special
      decontamination procedures in order to prevent accidental transmission of these
      pathogens by surgical instruments. In the search for effective, instrument
      compatible and routinely applicable decontamination procedures, a previous study
      [Lemmer, K., Mielke, M., Pauli, G. & Beekes, M. (2004). J Gen Virol 85, 3805
      3816] identified promising reagents in an in vitro carrier assay using steel
      wires contaminated with the disease-associated prion protein, PrP(Sc). In the
      follow-up study presented here, these reagents were validated for their
      decontamination potential in vivo. Steel wires initially loaded with >or=3 x
      10(5) LD(50) of 263K scrapie infectivity were implanted into the brains of
      hamsters after treatment for decontamination and subsequently monitored for their
      potential to trigger clinical disease or subclinical cerebral PrP(Sc) deposition
      within an observation period of 500 days. It was found that routinely usable
      reagents such as a commercially available alkaline cleaner (pH 12.2) applied for
      1 h at 23 degrees C or for 10 min at 55 degrees C and a mixture of 0.2 % SDS and
      0.3 % NaOH (pH 12.8) applied for 5 or 10 min at 23 degrees C achieved removal of
      263K scrapie infectivity below the threshold of detection (titre reduction of
      >or=5.5 log(10) units). The increasing use during the past few years of similar
      model systems by different research groups will facilitate comparison and
      integration of findings on the decontamination of steel surfaces from prions.
      Methods identified as highly effective in the 263K steel wire model need to be
      validated for human TSE agents on different types of instrument surfaces.

PMID- 18089761
TI  - Oxidative stress-induced insulin resistance in rat skeletal muscle: role of
      glycogen synthase kinase-3.
AB  - Oxidative stress can contribute to the multifactorial etiology of whole body and
      skeletal muscle insulin resistance. No investigation has directly assessed the
      effect of an in vitro oxidant stress on insulin action in intact mammalian
      skeletal muscle. Therefore, the purpose of the present study was to characterize
      the molecular actions of a low-grade oxidant stress (H(2)O(2)) on insulin
      signaling and glucose transport in isolated skeletal muscle of lean Zucker rats.
      Soleus strips were incubated in 8 mM glucose for 2 h in the absence or presence
      of 100 mU/ml glucose oxidase, which produces H(2)O(2) at approximately 90 microM.
      By itself, H(2)O(2) significantly (P < 0.05) activated basal glucose transport
      activity, net glycogen synthesis, and glycogen synthase activity and increased
      phosphorylation of insulin receptor (Tyr), Akt (Ser(473)), and GSK-3beta
      (Ser(9)). In contrast, this oxidant stress significantly inhibited the expected
      insulin-mediated enhancements in glucose transport, glycogen synthesis, and these
      signaling factors and allowed GSK-3beta to retain a more active form. In the
      presence of CT-98014, a selective GSK-3 inhibitor, the ability of insulin to
      stimulate glucose transport and glycogen synthesis during exposure to this
      oxidant stress was enhanced by 20% and 39% (P < 0.05), respectively, and insulin
      stimulation of the phosphorylation of insulin receptor, Akt, and GSK-3 was
      significantly increased by 36-58% (P < 0.05). These results indicate that an
      oxidant stress can directly and rapidly induce substantial insulin resistance of
      skeletal muscle insulin signaling, glucose transport, and glycogen synthesis.
      Moreover, a small, but significant, portion of this oxidative stress-induced
      insulin resistance is associated with a reduced insulin-mediated suppression of
      the active form of GSK-3beta.

PMID- 18089762
TI  - Studies of UCP2 transgenic and knockout mice reveal that liver UCP2 is not
      essential for the antiobesity effects of fish oil.
AB  - Uncoupling protein 2 (UCP2) is a possible target molecule for energy dissipation.
      Many dietary fats, including safflower oil and lard, induce obesity in C57BL/6
      mice, whereas fish oil does not. Fish oil increases UCP2 expression in
      hepatocytes and may enhance UCP2 activity by activating the UCP2 molecule or
      altering the lipid bilayer environment. To examine the role of liver UCP2 in
      obesity, we created transgenic mice that overexpressed human UCP2 in hepatocytes
      and examined whether UCP2 transgenic mice showed less obesity when fed a high-fat
      diet (safflower oil or lard). In addition, we examined whether fish oil had
      antiobesity effects in UCP2 knockout mice. UCP2 transgenic and wild-type mice fed
      a high-fat diet (safflower oil or lard) developed obesity to a similar degree.
      UCP2 knockout and wild-type mice fed fish oil had lower rates of obesity than
      mice fed safflower oil. Remarkably, safflower oil did not induce obesity in
      female UCP2 knockout mice, an unexpected phenotype for which we presently have no
      explanation. However, this unexpected effect was not observed in male UCP2
      knockout mice or in UCP2 knockout mice fed a high-lard diet. These data indicate
      that liver UCP2 is not essential for fish oil-induced decreases in body fat.

PMID- 18089763
TI  - Acute responses of muscle protein metabolism to reduced blood flow reflect
      metabolic priorities for homeostasis.
AB  - The present experiment was designed to measure the synthetic and breakdown rates
      of muscle protein in the hindlimb of rabbits with or without clamping the femoral
      artery. l-[ring-(13)C(6)]phenylalanine was infused as a tracer for measurement of
      muscle protein kinetics by means of an arteriovenous model, tracer incorporation,
      and tracee release methods. The ultrasonic flowmeter, dye dilution, and
      microsphere methods were used to determine the flow rates in the femoral artery,
      in the leg, and in muscle capillary, respectively. The femoral artery flow
      accounted for 65% of leg flow. A 50% reduction in the femoral artery flow reduced
      leg flow by 28% and nutritive flow by 26%, which did not change protein synthetic
      or breakdown rate in leg muscle. Full clamp of the femoral artery reduced leg
      flow by 42% and nutritive flow by 59%, which decreased (P < 0.05) both the
      fractional synthetic rate from 0.19 +/- 0.05 to 0.14 +/- 0.03%/day and fractional
      breakdown rate from 0.28 +/- 0.07 to 0.23 +/- 0.09%/day of muscle protein.
      Neither the partial nor full clamp reduced (P = 0.27-0.39) the intracellular
      phenylalanine concentration or net protein balance in leg muscle. We conclude
      that the flow threshold to cause a fall of protein turnover rate in leg muscle
      was a reduction of 30-40% of the leg flow. The acute responses of muscle protein
      kinetics to the reductions in blood flow reflected the metabolic priorities to
      maintain muscle homeostasis. These findings cannot be extrapolated to more
      chronic conditions without experimental validation.

PMID- 18089764
TI  - Screening for colorectal cancer in elderly persons: who should we screen and when
      can we stop?
AB  - OBJECTIVE: The aim of this study was to quantify the impact of age on the
      potential benefits of screening for colorectal cancer. METHOD: Life-table
      analysis of the risks of dying from colorectal cancer or from all other causes
      was performed. The impact of prematurely stopping screening was compared to the
      maximal potential benefit expected from lifelong screening. RESULTS: The relative
      proportion of deaths from colorectal cancer compared to all other causes was
      greatest at the age of 62 and diminished thereafter. A total of 80% of the
      maximal benefit from screening was achieved by screening till the age of 82. The
      impact of prematurely stopping screening varied with gender and race. DISCUSSION:
      The maximal societal benefit will be achieved by screening at younger ages
      because of competing causes of mortality among older people. Gender and ethnicity
      should be considered in individual decisions to stop screening at a given age.

PMID- 18089765
TI  - The multiple sources of women's aging anxiety and their relationship with
      psychological distress.
AB  - OBJECTIVE: The authors examine associations of three sources of women's aging
      anxiety--declining attractiveness, health, and fertility--with social contexts of
      their lives, including locations in systems of inequality, connections to
      institutions, relationships, and health. They also explore links between aging
      anxieties and distress. METHOD: Employing data from the National Survey of
      Midlife Development in the United States conducted in 1995-1996, the authors use
      logistic and OLS regression. RESULTS: Anxiety about attractiveness is higher
      among women who are younger, White, heterosexual, employed, separated/divorced,
      less financially independent, and have worse relationships. Anxiety about health
      is greater among women who are younger, White, less financially independent, and
      have worse relationships and health. Anxiety about fertility is higher among
      younger, more educated, heterosexual, more financially independent, and childless
      women. Anxiety about health and attractiveness predicts greater distress.
      DISCUSSION: This study suggests that correlates and mental health consequences of
      aging anxiety differ across sources of concern.

PMID- 18089766
TI  - Cohabitation status and onset of disability among older Danes: is social
      participation a possible mediator?
AB  - OBJECTIVE: To investigate the effect of cohabitation status in older men and
      women on (a) onset of disability at 3- and 4.5-year follow-up and (b) changes in
      functional ability between 3- and 4.5-year follow-up, and to analyze whether this
      effect was mediated by social participation. METHOD: A total of 2,533 nondisabled
      older men and women enrolled in the Danish Intervention Study on Preventive Home
      Visits constituted the study population. Data were collected by mailed
      questionnaires in 1998-1999, 2000, 2001-2002, and 2003. RESULTS: Living alone
      significantly increased the risk of onset of disability (T3 OR = 1.60[1.06-2.43],
      T4 OR = 1.74[1.22-2.47]) and the risk of sustained poor functional ability (OR =
      2.35[1.44-3.84]) among men, but not among single-living women. Social
      participation mediated only a small part of the effect of cohabitation status on
      functional ability. DISCUSSION: Our results underline the importance of
      cohabitation/marriage for maintaining a high functional ability among older men.

PMID- 18089767
TI  - Testing measurement reliability in older populations: methods for informed
      discrimination in instrument selection and application.
AB  - OBJECTIVE: The authors recommend confidence intervals as measures of precision
      for reliability coefficients, regression modeling as supplements for such omnibus
      reliability statistics, and unreliability detection as a goal of reliability
      testing distinct from reliability inference. METHODS: Illustrative reliability
      analyses are conducted on measures selected from a study of clinical features
      associated with urinary tract infection in older nursing home residents. RESULTS:
      Standard methods for reliability testing (e.g., kappa coefficients) are often
      inappropriate for small samples, and exact methods or descriptive reliability
      statistics are viable alternatives. DISCUSSION: Supplementation of omnibus
      statistics by loglinear regression modeling is especially appropriate for aging
      research because it facilitates tests of marginal homogeneity and comparisons of
      reliability results for relatively young and old subgroups. Latent class
      regression analysis is useful for older samples because multifactorial health
      conditions are often measured in multiple ways and assessment of their
      reliability can be integrated, granting certain assumptions, with validity
      assessment.

PMID- 18089768
TI  - Income health inequalities among older persons: the mediating role of multiple
      risk exposures.
AB  - OBJECTIVE: We examine whether the pervasive income gradient in health among
      senior citizens can be explained in part by multiple risk exposure. METHOD: A
      representative sample of 457 older persons (M = 74.29 years) living independently
      at home were assessed in a longitudinal study. Health was assessed with a
      standard self-report index. Risks included loss of a loved one, caregiver burden,
      low housing quality, and low social integration. RESULTS: The prospective link
      between income and subsequent health 2 years later is largely explained by
      exposure to a confluence of multiple risk factors during the 2-year period. These
      findings incorporate controls for negative affectivity. DISCUSSION: Low-income,
      older persons are significantly more likely to have lost a loved one or close
      friend, be burdened by extensive caregiving demands for someone else, be more
      socially isolated, and live in lower quality housing. These risk exposures, in
      turn, largely account for the prospective link between income and health.

PMID- 18089769
TI  - Review: how do hospital organizational structure and processes affect quality of
      care?: a critical review of research methods.
AB  - Interest in organizational contributions to the delivery of care has risen
      significantly in recent years. A challenge facing researchers, practitioners, and
      policy makers is identifying ways to improve care by improving the organizations
      that provide this care, given the complexity of health care organizations and the
      role organizations play in influencing systems of care. This article reviews the
      literature on the relationship between the structural characteristics and
      organizational processes of hospitals and quality of care. The review uses
      Donabedian's structure-process-outcome and level of analysis frameworks to
      organize the literature. The results of this review indicate that a preponderance
      of studies are conducted at the hospital level of analysis and are predominantly
      focused on the organizational structure-quality outcome relationship. The article
      concludes with recommendations of how health services researchers can expand
      their research to enhance one's understanding of the relationship between
      organizational characteristics and quality of care.

PMID- 18089770
TI  - Pharmacokinetics of PC-SOD, a lecithinized recombinant superoxide dismutase,
      after single- and multiple-dose administration to healthy Japanese and Caucasian
      volunteers.
AB  - To study the pharmacokinetics of single increasing intravenous doses (40-160 mg)
      and repeated doses (80 mg for 7 days) of lecithinized superoxide dismutase (PC
      SOD) in Japanese volunteers and to compare the pharmacokinetics of PC-SOD between
      Caucasians and Japanese. The Japanese study consisted of 2 parts: a single-dose,
      open-label, dose-escalation part and a multiple-dose, single-blind, placebo
      controlled part. The pharmacokinetics of PC-SOD were determined using
      noncompartmental and compartmental methods. Pharmacokinetic data from a study
      with PC-SOD in Caucasians were reanalyzed using the same methodology. The mean
      (SD) terminal half-life of PC-SOD in Japanese subjects was 25 (4) hours for the
      40-mg and 80-mg doses and 31 (15) hours for the 160-mg dose. There was
      nonlinearity between dose-normalized C(max) and clearance (P values .002 and
      .022). After multiple dosing, steady state was reached after 5 days. The observed
      accumulation ratio was 2.6 (0.5). The pharmacokinetics of the single 80-mg dose
      were similar for Japanese and Caucasians. The pharmacokinetics of PC-SOD was
      shown to be nonlinear with dose, which may be attributable to a saturable
      clearing mechanism. The relatively long half-life of PC-SOD (>24 hours) suggests
      that it is worthwhile to study the compound as a protective agent in clinical
      conditions with free radical overload.

PMID- 18089771
TI  - Aberrant gene expression patterns in placentomes are associated with
      phenotypically normal and abnormal cattle cloned by somatic cell nuclear
      transfer.
AB  - Transcription profiling of placentomes derived from somatic cell nuclear transfer
      (SCNT, n = 20), in vitro fertilization (IVF, n = 9), and artificial insemination
      (AI, n = 9) at or near term development was performed to better understand why
      SCNT and IVF often result in placental defects, hydrops, and large offspring
      syndrome (LOS). Multivariate analysis of variance was used to distinguish the
      effects of SCNT, IVF, and AI on gene expression, taking into account the effects
      of parturition (term or preterm), sex of fetus, breed of dam, breed of fetus, and
      pathological finding in the offspring (hydrops, normal, or other abnormalities).
      Differential expression of 20 physiologically important genes was confirmed with
      quantitative PCR. The largest effect on placentome gene expression was
      attributable to whether placentas were collected at term or preterm (i.e.,
      whether the collection was because of disease or to obtain stage-matched
      controls) followed by placentome source (AI, IVF, or SCNT). Gene expression in
      SCNT placentomes was dramatically different from AI (n = 336 genes; 276 >2-fold)
      and from IVF (n = 733 genes; 162 >2-fold) placentomes. Functional analysis of
      differentially expressed genes (DEG) showed that IVF has significant effects on
      genes associated with cellular metabolism. In contrast, DEG associated with SCNT
      are involved in multiple pathways, including cell cycle, cell death, and gene
      expression. Many DEG were shared between the gene lists for IVF and SCNT
      comparisons, suggesting that common pathways are affected by the embryo culture
      methods used for IVF and SCNT. However, the many unique gene functions and
      pathways affected by SCNT suggest that cloned fetuses may be starved and
      accumulating toxic wastes due to placental insufficiency caused by reprogramming
      errors. Many of these genes are candidates for hydrops and LOS.

PMID- 18089772
TI  - Clonal selection of metastasis within the life history of a tumor.

PMID- 18089773
TI  - Adaptation versus selection: the origins of metastatic behavior.

PMID- 18089774
TI  - Discovery of epigenetically silenced genes by methylated DNA immunoprecipitation
      in colon cancer cells.
AB  - CpG island promoter hypermethylation of tumor suppressor genes is a common
      hallmark of human cancer, and new large-scale epigenomic technologies might be
      useful in our attempts to define the complete DNA hypermethylome of tumor cells.
      Here, we report a functional search for hypermethylated CpG islands using the
      colorectal cancer cell line HCT-116, in which two major DNA methyltransferases,
      DNMT1 and DNMT3b, have been genetically disrupted (DKO cells). Using methylated
      DNA immunoprecipitation methodology in conjunction with promoter microarray
      analyses, we found that DKO cells experience a significant loss of
      hypermethylated CpG islands. Further characterization of these candidate
      sequences shows CpG island promoter hypermethylation and silencing of genes with
      potentially important roles in tumorigenesis, such as the Ras guanine nucleotide
      releasing factor (RASGRF2), the apoptosis-associated basic helix-loop
      transcription factor (BHLHB9), and the homeobox gene (HOXD1). Hypermethylation of
      these genes occurs in premalignant lesions and accumulates during tumorigenesis.
      Thus, our results show the usefulness of DNMT genetic disruption strategies
      combined with methylated DNA immunoprecipitation in searching for unknown
      hypermethylated candidate genes in human cancer that might aid our understanding
      of the biology of the disease and be of potential translational use.

PMID- 18089775
TI  - Human cancer cells commonly acquire DNA damage during mitotic arrest.
AB  - The mitotic checkpoint is a mechanism that arrests the progression to anaphase
      until all chromosomes have achieved proper attachment to mitotic spindles. In
      cancer cells, satisfaction of this checkpoint is frequently delayed or prevented
      by various defects, some of which have been causally implicated in tumorigenesis.
      At the same time, deliberate induction of mitotic arrest has proved clinically
      useful, as antimitotic drugs that interfere with proper chromosome-spindle
      interactions are effective anticancer agents. However, how mitotic arrest
      contributes to tumorigenesis or antimitotic drug toxicity is not well defined.
      Here, we report that mitotic chromosomes can acquire DNA breaks during both
      pharmacologic and genetic induction of mitotic arrest in human cancer cells.
      These breaks activate a DNA damage response, occur independently of cell death,
      and subsequently manifest as karyotype alterations. Such breaks can also occur
      spontaneously, particularly in cancer cells containing mitotic spindle
      abnormalities. Moreover, we observed evidence of some breakage in primary human
      cells. Our findings thus describe a novel source of DNA damage in human cells.
      They also suggest that mitotic arrest may promote tumorigenesis and antimitotic
      toxicity by provoking DNA damage.

PMID- 18089776
TI  - A Smac mimetic rescue screen reveals roles for inhibitor of apoptosis proteins in
      tumor necrosis factor-alpha signaling.
AB  - Smac mimetic compounds targeting the inhibitor of apoptosis proteins (IAP)
      baculoviral IAP repeat-3 domain are presumed to reduce the threshold for
      apoptotic cell death by alleviating caspase-9 repression. We explored this tenet
      in an unbiased manner by searching for small interfering RNAs that are able to
      confer resistance to the Smac mimetic compound LBW242. Among the screening hits
      were multiple components of the tumor necrosis factor alpha (TNFalpha) signaling
      pathway as well as X-linked inhibitor of apoptosis (XIAP) itself. Here, we show
      that in a subset of highly sensitive tumor cell lines, activity of LBW242 is
      dependent on TNFalpha signaling. Mechanistic studies indicate that in this
      context, XIAP is a positive modulator of TNFalpha induction whereas cellular
      inhibitor of apoptosis protein 1 negatively regulates TNFalpha-mediated
      apoptosis.

PMID- 18089777
TI  - Adenovirus-based strategies overcome temozolomide resistance by silencing the O6
      methylguanine-DNA methyltransferase promoter.
AB  - Currently, the most efficacious treatment for malignant gliomas is temozolomide;
      however, gliomas expressing the DNA repair enzyme O(6)-methylguanine-DNA
      methyltransferase (MGMT) are resistant to this drug. Strong clinical evidence
      shows that gliomas with methylation and subsequent silencing of the MGMT promoter
      are sensitive to temozolomide. Based on the fact that adenoviral proteins
      directly target and inactivate key DNA repair genes, we hypothesized that the
      oncolytic adenovirus Delta-24-RGD could be successfully combined with
      temozolomide to overcome the reported MGMT-mediated resistance. Our studies
      showed that the combination of Delta-24-RGD and temozolomide induces a profound
      therapeutic synergy in glioma cells. We observed that Delta-24-RGD treatment
      overrides the temozolomide-mediated G(2)-M arrest. Furthermore, Delta-24-RGD
      infection was followed by down-modulation of the RNA levels of MGMT. Chromatin
      immunoprecipitation assays showed that Delta-24-RGD prevented the recruitment of
      p300 to the MGMT promoter. Importantly, using mutant adenoviruses and wild-type
      and dominant-negative forms of the p300 protein, we showed that Delta-24-RGD
      interaction with p300 was required to induce silencing of the MGMT gene. Of
      further clinical relevance, the combination of Delta-24-RGD and temozolomide
      significantly improved the survival of glioma-bearing mice. Collectively, our
      data provide a strong mechanistic rationale for the combination of oncolytic
      adenoviruses and temozolomide, and should propel the clinical testing of this
      therapy approach in patients with malignant gliomas.

PMID- 18089778
TI  - Caspase-8 interacts with the p85 subunit of phosphatidylinositol 3-kinase to
      regulate cell adhesion and motility.
AB  - Cell migration plays an important role in tumor cell invasion and metastasis.
      Previously, we reported that caspase-8 contributes to cell migration and
      adhesion, a novel nonapoptotic function of an established apoptotic factor.
      Herein, we report that pro-caspase-8 is capable of restoring cell
      migration/adhesion to caspase-8-null cells, establishing the first biological
      function of a pro-caspase. The catalytic activity of caspase-8 was not required
      for cell motility. Stimulation of motility with epidermal growth factor induced
      the phosphorylation of caspase-8 on tyrosine-380 and the interaction of caspase-8
      with the p85 alpha subunit of phosphatidylinositol 3-kinase. Tyrosine-380 was
      required for the restoration of cell motility and cell adhesion in caspase-8-null
      cells, demonstrating the importance of the caspase-8-p85 interaction for these
      nonapoptotic functions. These results suggest that caspase-8 phosphorylation
      converts it from a proapoptotic factor to a cell motility factor that, through
      tyrosine-380, interacts with p85, an established cell migration component.

PMID- 18089779
TI  - RIN1 is a breast tumor suppressor gene.
AB  - Breast cancer progression is driven by altered gene expression. We show that the
      RIN1 gene, which encodes a RAS effector regulating epithelial cell properties, is
      silenced in breast tumor cell lines compared with cultured human mammary
      epithelial cells. We also report that RIN1 is often reduced in human breast tumor
      cells compared with morphologically normal breast glandular cells. At least two
      silencing mechanisms seem to be involved. Overexpression of the transcription
      repressor SNAI1 (Snail) was observed in ZR75-1 cells, and SNAI1 knockdown
      restored RIN1 expression. In addition, DNA methylation within the RIN1 promoter
      and the first exon in KPL-1 cells suggested that epigenetic modifications may
      contribute to silencing, and demethylation was shown to restore RIN1 expression.
      Reexpression of RIN1 was shown to inhibit anchorage-independent growth in soft
      agar. In addition, RIN1 expression inhibited both the initiation and progression
      of tumorigenesis for two breast tumor cell lines in a mouse model, consistent
      with a tumor suppressor function. We also show that RIN1 acts as a negative
      regulator of tumor cell invasive growth and that this requires the ABL kinase
      signaling function of RIN1, suggesting a mechanism through which RIN1 silencing
      may contribute to breast cancer progression.

PMID- 18089780
TI  - Concordant epigenetic silencing of transforming growth factor-beta signaling
      pathway genes occurs early in breast carcinogenesis.
AB  - Human mammary epithelial cells (HMEC) grown under standard cell culture
      conditions enter a growth phase referred to as selection, but a subpopulation is
      able to escape from arrest and continue to proliferate. These cells, called post
      selection or variant HMECs, may be derived from progenitor cells found in normal
      mammary epithelium that subsequently acquire premalignant lesions, including
      p16(INK4A) promoter hypermethylation. Epigenetic silencing of tumor suppressor
      genes through DNA methylation and histone modification is an early event in
      tumorigenesis. A major challenge is to find genes or gene pathways that are
      commonly silenced to provide early epigenetic diagnostic and therapeutic cancer
      targets. To identify very early epigenetic events that occur in breast cancer, we
      used microarrays to screen for gene pathways that were suppressed in post
      selection HMECs but reactivated after treatment with the demethylation agent 5
      aza-2'-deoxycytidine. We found that several members of the transforming growth
      factor beta (TGF-beta) signaling pathway were consistently down-regulated in the
      post-selection HMEC populations, and this was associated with a marked decrease
      in Smad4 nuclear staining. Gene suppression was not associated with DNA
      methylation but with chromatin remodeling, involving a decrease in histone H3
      lysine 27 trimethylation and an increase in histone H3 lysine 9 dimethylation and
      deacetylation. These results show for the first time that TGF-beta2, its
      receptors TGF-beta R1 and TGF-beta R2, and activator thrombospondin-1 are
      concordantly suppressed early in breast carcinogenesis by histone modifications
      and indicate that the TGF-beta signaling pathway is a novel target for gene
      activation by epigenetic therapy.

PMID- 18089781
TI  - Endostatin overexpression inhibits lymphangiogenesis and lymph node metastasis in
      mice.
AB  - Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of
      angiogenesis and tumor growth. We studied the development of carcinogen-induced
      skin tumors in transgenic J4 mice overexpressing endostatin in their
      keratinocytes. Unexpectedly, we did not observe any differences in tumor
      incidence and multiplicity between these and control mice, nor in the rate of
      conversion of benign papillomas to malignant squamous cell carcinomas (SCC). We
      did find, however, that endostatin regulates the terminal differentiation of
      keratinocytes because the SCCs in the J4 mice were less aggressive and more often
      well differentiated than those in the control mice. We observed an inhibition of
      tumor angiogenesis by endostatin at an early stage in skin tumor development, but
      more strikingly, there was a significant reduction in lymphatic vessels in the
      papillomas and SCCs in association with elevated endostatin levels and also a
      significant inhibition of lymph node metastasis in the J4 mice. We showed that
      tumor-infiltrating mast cells strongly expressed vascular endothelial growth
      factor-C (VEGF-C), and that the accumulation of these cells was markedly
      decreased in the tumors of the J4 mice. Moreover, endostatin inhibited the
      adhesion and migration of murine MC/9 mast cells on fibronectin in vitro. Our
      data suggest that endostatin can inhibit tumor lymphangiogenesis by decreasing
      the VEGF-C levels in the tumors, apparently via inhibition of mast cell migration
      and adhesion, and support the view that the biological effects of endostatin are
      not restricted to endothelial cells because endostatin also regulates tumor
      associated inflammation and differentiation, and the phenotype of epithelial
      tumors.

PMID- 18089782
TI  - Hepatocellular carcinoma associated with liver-gender disruption in male mice.
AB  - Hepatocellular carcinoma (HCC) is a male-predominant cancer associated with
      chronic hepatitis. Like human viral hepatitis, murine Helicobacter hepaticus
      infection produces inflammation and HCC with a masculine bias. We used this model
      to identify potential mechanisms of male HCC predisposition. Male weanling A/JCr
      mice (n = 67) were gavaged with H. hepaticus or vehicle. At 1 year, mice were
      distributed into four groups: surgical castration, chemical castration,
      castration followed by dihydrotestosterone supplementation, or sexually intact
      controls. Responses to infection were compared with IFN-gamma challenge alone. At
      21 months, there was no significant difference in hepatitis between groups.
      Neither castration nor androgen receptor agonism altered tumor incidence.
      Infected mice with severe, but not mild, disease exhibited a mosaic of
      alterations to sexually dimorphic genes and microsomal long-chain fatty acids. By
      microarray, tumorigenic hepatitis was strongly associated with liver-gender
      disruption, defined as the loss of a gender-identifying hepatic molecular
      signature. IFN-gamma alone produced similar changes, demonstrating a role for
      proinflammatory cytokines in this process. In conclusion, hepatocarcinogenesis in
      male mice with chronic hepatitis is maturationally imprinted and androgen
      independent. Proinflammatory cytokines may promote HCC in a male-predominant
      fashion due to high sensitivity of the masculinized liver to loss of sex-specific
      transcriptional balance. Liver-gender disruption has pleiotropic implications for
      hepatic enzyme activity, lipid processing, nuclear receptor activation,
      apoptosis, and proliferation. We propose a multistep model linking chronic
      hepatitis to liver cancer through cytokine-mediated derangement of gender
      specific cellular metabolism. This model introduces a novel mechanism of
      inflammation-associated carcinogenesis consistent with male-predominant HCC risk.

PMID- 18089783
TI  - ARMS depletion facilitates UV irradiation induced apoptotic cell death in
      melanoma.
AB  - Tumor cells often aberrantly reexpress molecules that mediate proper embryonic
      development for advantageous growth or survival. Here, we report that ankyrin
      repeat-rich membrane spanning (ARMS), a transmembrane protein abundant in the
      developing and adult neural tissues, is overexpressed in melanoma, a tumor
      ontogenetically originating from neural crest. Immunohistochemical study of 79
      melanocytic lesions showed significantly increased expression of ARMS in primary
      malignant melanomas (92.9%) and metastatic melanoma (60.0%) in comparison with
      benign nevocellular nevi (26.7%). To investigate the role of ARMS in melanoma
      formation, murine B16F0 melanoma cells with stable knockdown of ARMS were
      established by RNA interference. Down-regulation of ARMS resulted in significant
      inhibition of anchorage-independent growth in soft agar and restrictive growth of
      melanoma in severe combined immunodeficient mice. Importantly, depletion of ARMS
      facilitated UVB-induced apoptosis in melanoma cells through inactivation of
      mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)
      kinase (MEK)/ERK. Addition of MEK inhibitor PD98059 further sensitized ARMS
      depleted melanoma cells to UVB-induced apoptosis, whereas constitutively active
      MEK rescued ARMS-depleted cells from apoptosis. We further showed that BRAF, a
      downstream signaling molecule of ARMS in ERK pathway, is not mutated as a
      constitutively active form in acral lentiginous melanoma; in contrast,
      BRAF(T1799A) mutation, which leads to constitutive activation of ERK signaling,
      was detected in 57.1% of superficial spreading melanoma. Our study suggests that
      overexpression of ARMS per se serves as one mechanism to promote melanoma
      formation by preventing stress-induced apoptotic death mediated by the MEK/ERK
      signaling pathway, especially in acral lentiginous melanoma, most of which does
      not harbor BRAF mutation.

PMID- 18089784
TI  - CDC25B involvement in the centrosome duplication cycle and in microtubule
      nucleation.
AB  - Centrosome amplification is frequently reported in human cancers, although the
      molecular mechanisms that are responsible for this remain unclear. There is
      significant evidence to support a role for cyclin-dependent kinase (CDK)-cyclin
      complexes in centrosome duplication. The activities of CDK-cyclin complexes are,
      in turn, regulated by the CDC25 family of phosphatases in a strict spatiotemporal
      manner, and we have recently reported that CDC25B localizes to the centrosomes
      from early S phase. In the present study, we have investigated the role of
      centrosomally localized CDC25B in centrosome duplication. We first observed that
      overexpression of CDC25B under an inducible promoter in S phase results in
      centrosome overduplication. We found that forced expression of wild-type but not
      phosphatase-inactive CDC25B at the centrosomes results in centrosome
      amplification, aberrant microtubule organization, and abnormal accumulation of
      gamma-tubulin. In contrast, inhibition of CDC25B phosphatase activity inhibits
      the assembly of interphase microtubules and the centrosomal localization of gamma
      tubulin. We propose that CDC25B is part of the pathway that controls the
      localization of gamma-tubulin to the centrosomes, thereby regulating centrosome
      duplication during S phase and the nucleation of microtubules. We speculate that
      abnormal expression of CDC25B in numerous human tumors might therefore have a
      critical role in centrosome amplification and genomic instability.

PMID- 18089785
TI  - Integrated profiling of basal and luminal breast cancers.
AB  - Basal and luminal are two molecular subtypes of breast cancer with opposite
      histoclinical features. We report a combined, high-resolution analysis of genome
      copy number and gene expression in primary basal and luminal breast cancers.
      First, we identified and compared genomic alterations in 45 basal and 48 luminal
      tumors by using 244K oligonucleotide array comparative genomic hybridization
      (aCGH). We found various genome gains and losses and rare high-level gene
      amplifications that may provide therapeutic targets. We show that gain of 10p is
      a new alteration in basal breast cancer and that a subregion of the 8p12
      amplification is specific of luminal tumors. Rare high-level amplifications
      contained BCL2L2, CCNE, EGFR, FGFR2, IGF1R, NOTCH2, and PIK3CA. Potential gene
      breaks involved ETV6 and FLT3. Second, we analyzed both aCGH and gene expression
      profiles for 42 basal and 32 luminal breast cancers. The results support the
      existence of specific oncogenic pathways in basal and luminal breast cancers,
      involving several potential oncogenes and tumor suppressor genes (TSG). In basal
      tumors, 73 candidate oncogenes were identified in chromosome regions 1q21-23,
      10p14, and 12p13 and 28 candidate TSG in regions 4q32-34 and 5q11-23. In luminal
      breast cancers, 33 potential oncogenes were identified in 1q21-23, 8p12-q21,
      11q13, and 16p12-13 and 61 candidate TSG in 16q12-13, 16q22-24, and 17p13.
      HORMAD1 (P = 6.5 x 10(-5)) and ZNF703 (P = 7 x 10(-4)) were the most significant
      basal and luminal potential oncogenes, respectively. Finally, among 10p candidate
      oncogenes associated with basal subtype, we validated CDC123/C10orf7 protein as a
      basal marker.

PMID- 18089786
TI  - MUC1 oncoprotein regulates Bcr-Abl stability and pathogenesis in chronic
      myelogenous leukemia cells.
AB  - Chronic myelogenous leukemia (CML) results from expression of the Bcr-Abl fusion
      protein in hematopoietic stem cells. The MUC1 heterodimeric protein is aberrantly
      overexpressed in diverse human carcinomas. The present studies show that MUC1 is
      expressed in the human K562 and KU812 CML cell lines. The results show that MUC1
      associates with Bcr-Abl through a direct interaction between the Bcr N-terminal
      region and the MUC1 cytoplasmic domain. Stable silencing of MUC1 decreased
      cytoplasmic Bcr-Abl levels by promoting Bcr-Abl degradation. Silencing MUC1 was
      also associated with decreases in K562 and KU812 cell self-renewal capacity and
      with a more differentiated erythroid phenotype. The results further show that
      silencing MUC1 increases sensitivity of CML cells to imatinib-induced apoptosis.
      Analysis of primary CML blasts confirmed that, as found with the CML cell lines,
      MUC1 blocks differentiation and the apoptotic response to imatinib treatment.
      These findings indicate that MUC1 stabilizes Bcr-Abl and contributes to the
      pathogenesis of CML cells by promoting self renewal and inhibiting
      differentiation and apoptosis.

PMID- 18089787
TI  - Role of Rb-dependent and Rb-independent functions of papillomavirus E7 oncogene
      in head and neck cancer.
AB  - Infection with high-risk human papillomaviruses (HPV) and in particular the
      expression of the viral proteins E6 and E7 have been associated with the etiology
      of a subset of head and neck squamous cell cancer (HNSCC). However, the
      individual consequences of E6 and E7 expression in an in vivo model have not been
      examined in these tissues. We have used transgenes that direct expression of the
      HPV16 E6 and E7 proteins to the head and neck tissues of mice to dissect the
      contribution of these proteins to head and neck carcinogenesis. We report here
      that E7 is the major transforming oncogene in HPV-associated HNSCC, whereas E6 is
      more likely to play a secondary role in contributing to later stages of
      carcinogenesis. Furthermore, a conditional deletion of Rb, a prominent target for
      E7, in the same tissues did not recapitulate all E7-mediated phenotypes. Although
      our results do not preclude an important role for the E7-pRb interaction, they
      highlight the importance of pRb-independent functions of E7 in head and neck
      carcinogenesis.

PMID- 18089788
TI  - Flat colorectal cancers are genetically determined and progress to invasion
      without going through a polypoid stage.
AB  - Growing evidence suggests that flat colorectal cancers (CRC) account for 10% to
      20% of all CRCs and that these are frequently associated with more advanced
      pathologies. However, controversy exists as to the origin and progression of flat
      CRCs compared with the more common polypoid-type morphology. We report using the
      azoxymethane mouse model for human CRC that KK/HIJ and I/LNJ mice develop
      different frequencies of flat and polypoid tumors; 83% of colon tumors in I/LNJ
      mice are flat compared with only 19% in KK/HIJ mice, indicating a strong genetic
      predisposition to the development of specific CRC morphologies. Like polypoid
      tumors, all flat tumors show a significant increase in the level of nuclear beta
      catenin (CATNNB1), supported by similar frequencies of mutations in the
      phosphorylation domain-coding region (codons 32-41) of Catnnb1. However, in
      contrast to previous reports, tumors bearing higher "oncogenic potential" do not
      cluster in codon 41 of Catnnb1. There are no differences between flat and
      polypoid tumors in the frequency of mutations in codons 12 and 13 of Kras or
      codon 624 of Braf. Similarly, there are no differences between tumor morphologies
      in their location along the proximal-to-distal colonic axis or in the relative
      quantity of intratumor stromal myofibroblasts as marked by the expression of
      alpha-smooth muscle actin. Using a combination of serial colonoscopic and
      histologic analyses, we definitively show that flat CRCs do not develop de novo
      but progress through a flat adenomatous stage to invasive carcinoma without
      transit through an intermediary polypoid stage.

PMID- 18089789
TI  - Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic
      biomarker and a therapeutic target for lung and esophageal carcinomas.
AB  - Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and
      esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6
      complex locus K (LY6K) was specifically expressed in testis and transactivated in
      a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and
      265 ESCC specimens confirmed that LY6K overexpression was associated with poor
      prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and
      multivariate analysis confirmed its independent prognostic value for NSCLC (P =
      0.0035). We established an ELISA to measure serum LY6K and found that the
      proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC and 26 of
      81 (32.1%) ESCC, whereas only 3 of 74 (4.1%) healthy volunteers were falsely
      diagnosed. In most cases, there was no correlation between serum LY6K and
      conventional tumor markers of carcinoembryonic antigen (CEA) and cytokeratin 19
      fragment (CYFRA 21-1) values. A combined ELISA for both LY6K and CEA classified
      64.7% of lung adenocarcinoma patients as positive, and the use of both LY6K and
      CYFRA 21-1 increased sensitivity in the detection of lung squamous cell
      carcinomas and ESCCs up to 70.4% and 52.5%, respectively, whereas the false
      positive rate was 6.8% to 9.5%. In addition, knocked down of LY6K expression with
      small interfering RNAs resulted in growth suppression of the lung and esophageal
      cancer cells. Our data imply that a cancer-testis antigen, LY6K, should be useful
      as a new type of tumor biomarker and probably as a target for the development of
      new molecular therapies for cancer treatment.

PMID- 18089790
TI  - Altered MicroRNA expression confined to specific epithelial cell subpopulations
      in breast cancer.
AB  - MicroRNAs (miRNAs) are a new class of short noncoding regulatory RNAs (18-25
      nucleotides) that are involved in diverse developmental and pathologic processes.
      Altered miRNA expression has been associated with several types of human cancer.
      However, most studies did not establish whether miRNA expression changes occurred
      within cells undergoing malignant transformation. To obtain insight into miRNA
      deregulation in breast cancer, we implemented an in situ hybridization (ISH)
      method to reveal the spatial distribution of miRNA expression in archived
      formalin-fixed, paraffin-embedded specimens representing normal and tumor tissue
      from >100 patient cases. Here, we report that expression of miR-145 and miR-205
      was restricted to the myoepithelial/basal cell compartment of normal mammary
      ducts and lobules, whereas their accumulation was reduced or completely
      eliminated in matching tumor specimens. Conversely, expression of other miRNAs
      was detected at varying levels predominantly within luminal epithelial cells in
      normal tissue; expression of miR-21 was frequently increased, whereas that of let
      7a was decreased in malignant cells. We also analyzed the association of miRNA
      expression with that of epithelial markers; prognostic indicators such as
      estrogen receptor, progesterone receptor, and HER2; as well as clinical outcome
      data. This ISH approach provides a more direct and informative assessment of how
      altered miRNA expression contributes to breast carcinogenesis compared with miRNA
      expression profiling in gross tissue biopsies. Most significantly, early
      manifestation of altered miR-145 expression in atypical hyperplasia and carcinoma
      in situ lesions suggests that this miRNA may have a potential clinical
      application as a novel biomarker for early detection.

PMID- 18089791
TI  - Inhibition of membrane-type 1 matrix metalloproteinase at cell-matrix adhesions.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP) has been implicated in tumor
      invasion and metastasis. We previously reported that extracellular matrix
      degradation by MT1-MMP regulates cell migration via modulating sustained integrin
      mediated signals. In this study, MT1-MMP-expressing cells were plated onto
      fibronectin-coated plates and monitored for cell-matrix adhesion formation and
      fibronectin degradation. The fibronectin was degraded and removed in line with
      the cell migration track. The migrating cells showed a polarized morphology and
      were in contact with the edge of fibronectin through the leading edge, in which
      cell-matrix adhesions are concentrated. Expression of MT1-MMP targeted to cell
      matrix adhesions by fusing with the focal adhesion targeting (FAT) domain of
      focal adhesion kinase (FAK) promoted the initial fibronectin lysis at the cell
      periphery immediately after adhesion. These results suggest that fibronectin is
      degraded by MT1-MMP located at cell-matrix adhesions, which are concentrated at
      the leading edge of the migrating cells. To inhibit MT1-MMP at cell-matrix
      adhesion, the dominant negative form of MT1-MMP (MT1-Pex) was targeted to the
      cell-matrix adhesion by fusing with the FAT domain (MT1-Pex-FAT). MT1-Pex-FAT
      accumulated at cell-matrix adhesions and inhibited fibronectin degradation as
      well as FAK phosphorylation more effectively than parental MT1-Pex. MT1-Pex-FAT
      was also shown to suppress the invasion of tumor cells into three-dimensional
      collagen gel more strongly than MT1-Pex. These results suggest that MT1-MMP
      mediated extracellular matrix lysis at cell-matrix adhesions induces the
      establishment of cell polarity, which facilitates cell-matrix adhesion turnover
      and subsequent cell migration. This model highlights the role of MT1-MMP at the
      leading edge of migrating cells.

PMID- 18089793
TI  - Lack of mutagenicity of acrolein-induced DNA adducts in mouse and human cells.
AB  - Acrolein is an endogenous metabolite and a ubiquitous environmental pollutant.
      Recently, it has been suggested that acrolein is a major etiologic agent for
      tobacco smoking-related lung cancer. Despite the known DNA-damaging effects of
      acrolein, its mutagenicity to mammalian cells remains uncertain. We have
      investigated acrolein-induced DNA damage in relation to mutagenesis, with special
      focus on DNA repair, in mouse and human cells. We mapped the formation of
      acrolein-induced DNA adducts and the kinetics of repair of the induced lesions in
      the cII transgene, the mutational target, in acrolein-treated transgenic mouse
      fibroblasts. Acrolein-DNA adducts were formed preferentially at specific
      nucleotide positions, mainly at G:C base pairs, along the cII transgene. The
      induced acrolein-DNA adducts were moderately resistant to DNA repair.
      Quantification of cII mutant frequency in acrolein-treated cells, however,
      revealed that acrolein was not mutagenic to these cells at doses sufficient to
      produce DNA adducts. Determination of supF mutant frequency in DNA repair
      proficient and DNA repair-deficient human fibroblasts transfected with acrolein
      treated plasmids confirmed a lack of acrolein mutagenicity. Because CpG
      methylation may intensify acrolein-DNA adduction, we examined whether the extent
      of CpG methylation in the supF gene can determine acrolein-induced mutagenesis in
      human cells. Enhancement of acrolein-DNA adduction by methylating CpGs in the
      supF sequence did not elicit a mutagenic response in human fibroblasts, however.
      We conclude that acrolein is not mutagenic to mouse and human fibroblasts,
      regardless of DNA repair capacity or methylation status of CpGs, possibly because
      of a highly accurate replication bypass of the induced lesions.

PMID- 18089792
TI  - Implication of AMP-activated protein kinase and Akt-regulated survivin in lung
      cancer chemopreventive activities of deguelin.
AB  - Survivin plays important roles in maintaining cell proliferation and survival and
      promoting tumorigenesis. The present study was conducted to determine the stage
      of lung carcinogenesis at which survivin expression is induced and to investigate
      how survivin affects the chemopreventive action of deguelin. In in vitro studies,
      we observed higher levels of survivin expression in a subset of premalignant and
      malignant human bronchial epithelial (HBE) and non-small-cell lung cancer (NSCLC)
      cell lines than in normal HBE cells, and in in vivo studies, a higher level of
      survivin expression in specimen of human lung dysplasia than in normal lung
      specimens. Treatment with deguelin inhibited de novo synthesis of survivin
      protein and induced apoptosis, resulting in suppression of transformation
      phenotypes, in the premalignant and malignant HBE and NSCLC cell lines. Deguelin
      inhibited survivin expression in tuberous sclerosis complex 2 (TSC2) wild-type
      mouse embryonic fibroblasts (MEF) but not in TSC2-knockout MEFs in which
      mammalian target of rapamycin (mTOR) is constitutively active. Deguelin induced
      activation of AMP-activated protein kinase (AMPK) and inactivation of Akt.
      Overexpression of constitutively active Akt abolished deguelin-induced modulation
      of AMPK activity and survivin expression. Conversely, inactivation of AMPK by
      compound C or AMPKalpha1/2 small interfering RNA restored Akt and mTOR activities
      and survivin expression in deguelin-treated HBE cells. These results suggest that
      survivin expression is induced as an early event in lung carcinogenesis, and
      deguelin acts as a chemopreventive agent by inducing a reciprocal regulation
      between AMPK and Akt, resulting in the inhibition of mTOR-mediated survivin.

PMID- 18089794
TI  - Different S/M checkpoint responses of tumor and non tumor cell lines to DNA
      replication inhibition.
AB  - Cell cycle checkpoint abrogation, especially the inhibition of Chk1 in
      combination with DNA-damaging treatments, has been proposed as a promising way of
      sensitizing cancer cells. However, less is known about the possibility to
      selectively affect tumor cells when they are treated with agents that block DNA
      synthesis in combination with replication checkpoint inhibitors. Here, we present
      clear insights in the different responses of tumor and non-transformed cells to
      the inhibition of DNA replication with hydroxyurea in combination with checkpoint
      abrogation via inhibition of Ataxia telangiectasia-mutated- (ATM) and Rad3
      related/ATM (ATR/ATM) and Chk1 kinases. Interestingly, we find that non
      transformed cell lines activate ATR/ATM- and Chk1-independent pathways in
      response to replication inhibition to prevent mitotic entry with unreplicated
      DNA. In contrast, tumor cell lines such as HCT116 and HeLa cells rely entirely on
      Chk1 activity for a proper response to replication inhibitors. Our results show
      that p38 is activated in response to hydroxyurea treatment and collaborates with
      Chk1 to prevent mitotic entry in non-transformed cell lines by maintaining cyclin
      B1/Cdk1 complexes inactive. Furthermore, DNA replication arrest down-regulates
      cyclin B1 promoter activity in non-transformed cells, but not in tumor cells in a
      Chk1- and p38-independent way. Thus, our data show that non-transformed cells
      present a more robust DNA replication checkpoint response compared with tumor
      cells that involves activation of the p38 pathway. We show that some of these
      responses to replication block can be lost in tumor cells, causing a defective
      checkpoint and providing a rationale for tumor-selective effects of combined
      therapies.

PMID- 18089795
TI  - BCL-2 and mutant NRAS interact physically and functionally in a mouse model of
      progressive myelodysplasia.
AB  - Myelodysplastic syndromes (MDS) are clonal stem cell hematologic disorders that
      evolve to acute myeloid leukemia (AML) and thus model multistep leukemogenesis.
      Activating RAS mutations and overexpression of BCL-2 are prognostic features of
      MDS/AML transformation. Using NRASD12 and BCL-2, we created two distinct models
      of MDS and AML, where human (h)BCL-2 is conditionally or constitutively
      expressed. Our novel transplantable in vivo models show that expression of hBCL-2
      in a primitive compartment by mouse mammary tumor virus-long terminal repeat
      results in a disease resembling human MDS, whereas the myeloid MRP8 promoter
      induces a disease with characteristics of human AML. Expanded leukemic stem cell
      (Lin(-)/Sca-1(+)/c-Kit(+)) populations and hBCL-2 in the increased RAS-GTP
      complex within the expanded Sca-1(+) compartment are described in both MDS/AML
      like diseases. Furthermore, the oncogenic compartmentalizations provide the
      proapoptotic versus antiapoptotic mechanisms, by activating extracellular signal
      regulated kinase and AKT signaling, in determination of the neoplastic phenotype.
      When hBCL-2 is switched off with doxycycline in the MDS mice, partial reversal of
      the phenotype was observed with persistence of bone marrow blasts and tissue
      infiltration as RAS recruits endogenous mouse (m)BCL-2 to remain active, thus
      demonstrating the role of the complex in the disease. This represents the first
      in vivo progression model of MDS/AML dependent on the formation of a BCL-2:RAS
      GTP complex. The colocalization of BCL-2 and RAS in the bone marrow of MDS/AML
      patients offers targeting either oncogene as a therapeutic strategy.

PMID- 18089796
TI  - Targeting the nuclear factor-kappaB rescue pathway has promising future in human
      renal cell carcinoma therapy.
AB  - Metastatic renal cell carcinoma (RCC) remains refractory to therapies. The
      nuclear factor-kappaB (NF-kappaB) transcription factor is involved in cell
      growth, cell motility, and vascularization. We evaluated whether targeting NF
      kappaB could be of therapeutic and prognostic values in human RCC. The activation
      of the NF-kappaB pathway in human RCC cells and tumors was investigated by
      Western blot. In vitro, the effects of BAY 11-7085 and sulfasalazine, two NF
      kappaB inhibitors, on tumor cell growth were investigated by cell counting, 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis, terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling, and fluorescence
      activated cell sorting. Their specificity toward NF-kappaB was analyzed by
      Western blot, confocal microscopy, NF-kappaB small interfering RNA, and NF-kappaB
      transcription assay. In vivo, the effects of BAY 11-7085 on the growth of human
      RCC tumors were investigated in nude mice. A tissue microarray (TMA) containing
      241 cases of human RCC with 12 to 22 years of clinical follow-up and
      corresponding normal tissues was built up to assess prognostic significance of
      activated NF-kappaB. NF-kappaB is constitutively activated in cultured cells
      expressing or not the von Hippel-Lindau (VHL) tumor suppressor gene as a
      consequence of Akt kinase activation and in tumors. In vitro and in vivo NF
      kappaB inhibition blocked tumor cell growth by inducing cell apoptosis. On the
      TMA, NF-kappaB activation was correlated with tumor dimension but was not found
      to be an independent prognostic factor for patient survival. This report provides
      strong evidence that the mechanisms responsible for the intrinsic resistance of
      RCC cells to apoptosis converge on NF-kappaB independently of VHL expression and
      that targeting this pathway has great anticancer potential.

PMID- 18089797
TI  - Functional diversity of human protection of telomeres 1 isoforms in telomere
      protection and cellular senescence.
AB  - Protection of telomeres 1 (POT1) proteins in various organisms bind telomeres and
      regulate their structure and function. In contrast to mice carrying two distinct
      POT1 genes encoding two POT1 proteins (POT1a and POT1b), humans have the single
      POT1 gene. In addition to full-length POT1 protein (variant v1), the human POT1
      gene encodes four other variants due to alternative RNA splicing (variants v2,
      v3, v4, and v5), whose functions are poorly understood. The functional analyses
      of the NH(2)-terminally and COOH-terminally truncated POT1 variants in this study
      showed that neither the single-stranded telomere-binding ability of the NH(2)
      terminal oligonucleotide-binding (OB) folds nor the telomerase-dependent telomere
      elongation activity mediated by the COOH-terminal TPP1-interacting domain was
      telomere protective by itself. Importantly, a COOH-terminally truncated variant
      (v5), which consists of the NH(2)-terminal OB folds and the central region of
      unknown function, was found to protect telomeres and prevent cellular senescence
      as efficiently as v1. Our data revealed mechanistic and functional differences
      between v1 and v5: (a) v1, but not v5, functions through the maintenance of
      telomeric 3' overhangs; (b) p53 is indispensable to v5 knockdown-induced
      senescence; and (c) v5 functions at only a fraction of telomeres to prevent DNA
      damage signaling. Furthermore, v5 was preferentially expressed in mismatch repair
      (MMR)-deficient cells and tumor tissues, suggesting its role in chromosome
      stability associated with MMR deficiency. This study highlights a human-specific
      complexity in telomere protection and damage signaling conferred by functionally
      distinct isoforms from the single POT1 gene.

PMID- 18089798
TI  - Tumor irradiation increases the recruitment of circulating mesenchymal stem cells
      into the tumor microenvironment.
AB  - Mesenchymal stem cells (MSC) migrate to and proliferate within sites of
      inflammation and tumors as part of the tissue remodeling process. Radiation
      increases the expression of inflammatory mediators that could enhance the
      recruitment of MSC into the tumor microenvironment. To investigate this,
      bilateral murine 4T1 breast carcinomas (expressing renilla luciferase) were
      irradiated unilaterally (1 or 2 Gy). Twenty-four hours later, 2 x 10(5) MSC
      expressing firefly luciferase were injected i.v. Mice were then monitored with
      bioluminescent imaging for expression of both renilla (tumor) and firefly (MSC)
      luciferase. Forty-eight hours postirradiation, levels of MSC engraftment were 34%
      higher in tumors receiving 2 Gy (P = 0.004) than in the contralateral
      unirradiated limb. Immunohistochemical staining of tumor sections from mice
      treated unilaterally with 2 Gy revealed higher levels of MSC in the parenchyma of
      radiated tumors, whereas a higher proportion of MSC remained vasculature
      associated in unirradiated tumors. To discern the potential mediators involved in
      MSC attraction, in vitro migration assays showed a 50% to 80% increase in MSC
      migration towards conditioned media from 1 to 5 Gy-irradiated 4T1 cells compared
      with unirradiated 4T1 cells. Irradiated 4T1 cells had increased expression of the
      cytokines, transforming growth factor-beta1, vascular endothelial growth factor,
      and platelet-derived growth factor-BB, and this up-regulation was confirmed by
      immunohistochemistry in tumors irradiated in vivo. Interestingly, the chemokine
      receptor CCR2 was found to be up-regulated in MSC exposed to irradiated tumor
      cells and inhibition of CCR2 led to a marked decrease of MSC migration in vitro.
      In conclusion, clinically relevant low doses of irradiation increase the tropism
      for and engraftment of MSC in the tumor microenvironment.

PMID- 18089799
TI  - The ataxia telangiectasia-mutated target site Ser18 is required for p53-mediated
      tumor suppression.
AB  - The p53 tumor suppressor is phosphorylated at multiple sites within its NH(2)
      terminal region. One of these phosphorylation sites (mouse Ser(18) and human
      Ser(15)) is a substrate for the ataxia telangiectasia-mutated (ATM) and ATM
      related (ATR) protein kinases. Studies of p53(S18A) mice (with a germ-line
      mutation that replaces Ser(18) with Ala) have indicated that ATM/ATR
      phosphorylation of p53 Ser(18) is required for normal DNA damage-induced PUMA
      expression and apoptosis but not for DNA damage-induced cell cycle arrest. Unlike
      p53-null mice, p53(S18A) mice did not succumb to early-onset tumors. This finding
      suggested that phosphorylation of p53 Ser(18) was not required for p53-dependent
      tumor suppression. Here we report that the survival of p53(S18A) mice was
      compromised and that they spontaneously developed late-onset lymphomas (between
      ages 1 and 2 years). These mice also developed several malignancies, including
      fibrosarcoma, leukemia, leiomyosarcoma, and myxosarcoma, which are unusual in p53
      mutant mice. Furthermore, we found that lymphoma development was linked with
      apoptotic defects. In addition, p53(S18A) animals exhibited several aging
      associated phenotypes early, and murine embryonic fibroblasts from these animals
      underwent early senescence in culture. Together, these data indicate that the
      ATM/ATR phosphorylation site Ser(18) on p53 contributes to tumor suppression in
      vivo.

PMID- 18089800
TI  - Novel noncatalytic role for caspase-8 in promoting SRC-mediated adhesion and Erk
      signaling in neuroblastoma cells.
AB  - Neuroblastomas are extremely aggressive, although heterogeneous, cancers with a
      poor prognosis upon metastasis. Some evidence has suggested a correlative
      silencing of caspase-8 with MYCN amplification in neuroblastoma. A prognostic
      effect of this silencing, however, has been disputed. We report here hitherto
      undescribed roles for caspase-8 in the modulation of cell adhesion and subsequent
      activation of the Erk signaling pathway. Re-expression of caspase-8 in
      neuroblastoma cells lacking endogenous caspase-8 expression was found to promote
      cell adhesion to extracellular matrix and to activate adhesion-dependent
      signaling pathways, such as the Erk kinase cascade. This function of caspase-8
      occurred irrespective of its proteolytic activity. Additionally, a pool of
      caspase-8 was shown to co-localize with the Src tyrosine kinase at the cellular
      periphery. Furthermore, our studies showed that caspase-8 forms a physical
      protein complex with Src via its death effector domains (DED) and maintains the
      complex in a detergent-soluble fraction. We also show that the DEDs of caspase-8
      alone are necessary and sufficient to recreate the adhesive and biochemical
      phenotypes observed with the full-length protein, suggesting that caspase-8 may
      exert these effects via its association with Src. This protein complex
      association of caspase-8 and Src, and concomitant downstream signaling events,
      may help reconcile why a potential tumor suppressor such as caspase-8 is rarely
      absent in cancers.

PMID- 18089801
TI  - mTORC2 activity is elevated in gliomas and promotes growth and cell motility via
      overexpression of rictor.
AB  - mTORC2 is a multimeric kinase composed of the mammalian target of rapamycin
      kinase (mTOR), mLST8, mSin1, and rictor. The complex is insensitive to acute
      rapamycin exposure and has shown functions in controlling cell growth and actin
      cytoskeletal assembly. mTORC2 has recently been shown to phosphorylate and
      activate Akt. Because approximately 70% of gliomas harbor high levels of
      activated Akt, we investigated whether mTORC2 activity was elevated in gliomas.
      In this study, we found that mTORC2 activity was elevated in glioma cell lines as
      well as in primary tumor cells as compared with normal brain tissue (P < 0.05).
      Moreover, we found that rictor protein and mRNA levels were also elevated and
      correlated with increased mTORC2 activity. Overexpression of rictor in cell lines
      led to increased mTORC2 assembly and activity. These lines exhibited increased
      anchorage-independent growth in soft agar, increased S-phase cell cycle
      distribution, increased motility, and elevated integrin beta(1) and beta(3)
      expression. In contrast, small interfering RNA-mediated knockdown of rictor
      inhibited these oncogenic activities. Protein kinase C alpha (PKC alpha) activity
      was shown to be elevated in rictor-overexpressing lines but reduced in rictor
      knockdown clones, consistent with the known regulation of actin organization by
      mTORC2 via PKC alpha. Xenograft studies using these cell lines also supported a
      role for increased mTORC2 activity in tumorigenesis and enhanced tumor growth. In
      summary, these data suggest that mTORC2 is hyperactivated in gliomas and
      functions in promoting tumor cell proliferation and invasive potential due to
      increased complex formation as a result of the overexpression of rictor.

PMID- 18089802
TI  - SNAI1 is required for tumor growth and lymph node metastasis of human breast
      carcinoma MDA-MB-231 cells.
AB  - The transcription factor, SNAI1 (Snail), has recently been proposed as an
      important mediator of tumor invasion because of its role in E-cadherin down
      regulation and induction of epithelial-mesenchymal transition. In human breast
      cancer, the expression of SNAI1 and/or the homologous SNAI2 (Slug) has been
      associated with E-cadherin repression, local or distant metastasis, tumor
      recurrence, or poor prognosis in different tumor series. However, the specific
      contribution of either factor to breast tumor progression is still unclear. We
      have analyzed the role of SNAI1 in human breast cancer by loss of function
      studies and provide evidence of a major role for SNAI1 in both primary tumor
      growth and metastasis of human breast carcinoma MDA-MB-231 cells. Specific
      silencing of SNAI1 by short hairpin RNA induces a decrease in mesenchymal and
      proinvasive markers (MMP9, ID1, SPARC) in MDA-MB-231 cells, concomitant with
      reduced in vitro invasive behavior. More importantly, stable SNAI1 silencing in
      MDA-MB-231 cells leads to a dramatic reduction of in vivo tumor incidence and
      growth rate. Tumors induced by MDA-MB-231-SNAI1-silenced cells show extensive
      necrotic regions and a significant decrease in invasive and angiogenic markers.
      Moreover, SNAI1 silencing increases the sensitivity of MDA-MB-231 cells to
      chemotherapeutics relevant in breast cancer treatments, gemcitabine and
      docetaxel. Remarkably, analysis of cell lines derived from lymph node metastasis
      indicates that SNAI1 expression is required for metastatic dissemination.

PMID- 18089803
TI  - A role for glial cell derived neurotrophic factor induced expression by
      inflammatory cytokines and RET/GFR alpha 1 receptor up-regulation in breast
      cancer.
AB  - By screening a tissue microarray of invasive breast tumors, we have shown that
      the receptor tyrosine kinase RET (REarranged during Transfection) and its
      coreceptor GFR alpha 1 (GDNF receptor family alpha-1) are overexpressed in a
      subset of estrogen receptor-positive tumors. Germ line-activating oncogenic
      mutations in RET allow this receptor to signal independently of GFR alpha 1 and
      its ligand glial cell-derived neurotrophic factor (GDNF) to promote a spectrum of
      endocrine neoplasias. However, it is not known whether tumor progression can also
      be driven by receptor overexpression and whether expression of GDNF, as has been
      suggested for other neurotrophic factors, is regulated in response to the
      inflammatory microenvironment surrounding many epithelial cancers. Here, we show
      that GDNF stimulation of RET(+)/GFR alpha 1(+) MCF7 breast cancer cells in vitro
      enhanced cell proliferation and survival, and promoted cell scattering. Moreover,
      in tumor xenografts, GDNF expression was found to be up-regulated on the
      infiltrating endogenous fibroblasts and to a lesser extent by the tumor cells
      themselves. Finally, the inflammatory cytokines tumor necrosis factor-alpha and
      interleukin-1 beta, which are involved in tumor promotion and development, were
      found to act synergistically to up-regulate GDNF expression in both fibroblasts
      and tumor cells. These data indicate that GDNF can act as an important component
      of the inflammatory response in breast cancers and that its effects are mediated
      by both paracrine and autocrine stimulation of tumor cells via signaling through
      the RET and GFR alpha 1 receptors.

PMID- 18089804
TI  - Green tea polyphenols reverse cooperation between c-Rel and CK2 that induces the
      aryl hydrocarbon receptor, slug, and an invasive phenotype.
AB  - Exposure to and bioaccumulation of lipophilic environmental pollutants, such as
      polycyclic aromatic hydrocarbons (PAHs), has been implicated in breast cancer.
      Treatment of female rats with the prototypic xenobiotic PAH 7,12
      dimethylbenz(a)anthracene (DMBA) induces mammary tumors with an invasive
      phenotype. Here, we show that green tea prevents or reverses loss of the
      epithelial marker E-cadherin on the surface of DMBA-induced in situ cancers. To
      investigate the mechanism(s) leading to a less invasive phenotype, the effects of
      the green tea polyphenol epigallocatechin-3 gallate (EGCG) on mammary tumor cells
      were assessed. EGCG reversed epithelial to mesenchymal transition (EMT) in DMBA
      treated NF-kappaB c-Rel-driven mammary tumor cells and reduced levels of c-Rel
      and the protein kinase CK2. Ectopic coexpression of c-Rel and CK2alpha in
      untransformed mammary epithelial cells was sufficient to induce a mesenchymal
      gene profile. Mammary tumors and cell lines derived from MMTV-c-Rel x CK2alpha
      bitransgenic mice displayed a highly invasive phenotype. Coexpression of c-Rel
      and CK2, or DMBA exposure induced the aryl hydrocarbon receptor (AhR) and
      putative target gene product Slug, an EMT master regulator, which could be
      reversed by EGCG treatment. Thus, activation of c-Rel and CK2 and downstream
      targets AhR and Slug by DMBA induces EMT; EGCG can inhibit this signaling.

PMID- 18089805
TI  - Nm23-H1 suppresses metastasis by inhibiting expression of the lysophosphatidic
      acid receptor EDG2.
AB  - Nm23-H1 transcriptionally down-regulates expression of the lysophosphatidic acid
      receptor EDG2 and this down-regulation is critical for Nm23-H1-mediated motility
      suppression in vitro. We investigated the effect of altered EDG2 expression on
      Nm23-H1-mediated metastasis suppression in vivo. Clonal MDA-MB-435-derived tumor
      cell lines transfected with Nm23-H1 together with either a vector control or EDG2
      had similar anchorage-dependent and anchorage-independent growth rates in vitro.
      However, a 45- and 300-fold inhibition of motility and invasion (P < 0.0001),
      respectively, was observed in Nm23-H1/vector lines, whereas coexpression of EDG2
      restored activity to levels observed in the parental line. Using fluorescently
      labeled cells and ex vivo microscopy, the capacity of these cells to adhere,
      arrest, extravasate, and survive in the murine lung over a 24-h time course was
      measured. Only 5% of Nm23-H1/vector-transfected cells were retained in the murine
      lung 6 h following tail vein injection; coexpression of EDG2 enhanced retention 8
      to 13-fold (P < 0.01). In a spontaneous metastasis assay, the primary tumor size
      of Nm23-H1/vector and Nm23-H1/EDG2 clones was not significantly different.
      However, restoration of EDG2 expression augmented the incidence of pulmonary
      metastasis from 51.9% to 90.4% (P = 2.4 x 10(-5)), comparable with parental MDA
      MB-435 cells. To determine the relevance of this model system to human breast
      cancer, a cohort of breast carcinomas was stained for Nm23-H1 and EDG2 and a
      statistically significant inverse correlation between these two proteins was
      revealed (r = -0.73; P = 0.004). The data indicate that Nm23-H1 down-regulation
      of EDG2 is functionally important to suppression of tumor metastasis.

PMID- 18089807
TI  - Cytosolic phospholipase A2 alpha regulates cell growth in RET/PTC-transformed
      thyroid cells.
AB  - Modulation of cytosolic phospholipase A(2) (PLA(2)) expression levels and
      production of its metabolites have been reported in several tumor types,
      indicating involvement of arachidonic acid and its derivatives in tumorigenesis.
      Following our demonstration that the PLA(2) group IV isoform alpha (PLA(2)IV
      alpha) controls TSH-independent growth of normal thyroid (PCCl(3)) cells, we have
      investigated the mitogenic role of PLA(2)IV alpha in rat thyroid cells
      transformed by the RET/PTC oncogenes (PC-PTC cells). We now report that PLA(2)IV
      alpha acts downstream of the RET/PTC oncogenes in a novel pathway controlling RET
      dependent cell proliferation. In addition, we show that PLA(2)IV alpha is in its
      phosphorylated/active form not only in RET/PTC-transformed cells and in cells
      derived from human papillary carcinomas but also in lysates from tumor tissues,
      thus relating constitutive activation of PLA(2)IV alpha to RET/PTC-dependent
      tumorigenesis. Moreover, p38 stress-activated protein kinase is the downstream
      effector of RET/PTC that is responsible for PLA(2)IV alpha phosphorylation and
      activity. In summary, our data elucidate a novel mechanism in the control of
      thyroid tumor cell growth that is induced by the RET/PTC oncogenes and which is
      distinguishable from that of other oncogenes, such as BRAF. This mechanism is
      mediated by PLA(2)IV alpha and should be amenable to targeted pharmacologic
      intervention.

PMID- 18089806
TI  - Galectin-3 cleavage: a novel surrogate marker for matrix metalloproteinase
      activity in growing breast cancers.
AB  - Failed therapies directed against matrix metalloproteinases (MMP) in cancer
      patients may be attributed, in part, to lack of diagnostic tools to differentiate
      between pro-MMPs and active MMPs, which indicate whether a treatment is
      efficacious or not. Because galectin-3 is cleavable in vitro by MMPs, we have
      developed differential antibodies recognizing its cleaved and noncleaved forms
      and tested their clinical utilization as a surrogate diagnostic marker for the
      presence of active MMPs in growing breast cancers. Wild-type and cleavage
      resistant galectin-3 were constructed and expressed in galectin-3-null human
      breast carcinoma cells (BT-549). Tumorigenic and angiogenic potential of the
      clones was studied by injections into nude mice. MMP-2, MMP-9, full-length, and
      cleaved galectin-3 were localized in the xenografts by immunohistochemical
      analysis of paraffin-embedded sections using specific antibodies. Activities of
      MMP-2/9 were corroborated by in situ zymography on frozen tissue sections.
      Galectin-3 cleavage was shown in vivo by differential antibody staining and
      colocalized with predicted active MMPs both in mouse xenografts and human breast
      cancer specimens. In situ zymography validated these results. In addition, BT-549
      cells harboring noncleavable galectin-3 showed reduced tumor growth and
      angiogenesis compared with the wild-type. We conclude that galectin-3 cleavage is
      an active process during tumor progression and could be used as a simple, rapid,
      and reliable surrogate marker for the activities of MMPs in growing breast
      cancers.

PMID- 18089808
TI  - Hsp27 modulates p53 signaling and suppresses cellular senescence.
AB  - The small heat shock protein Hsp27 is expressed at high levels in many tumors and
      provides protection against anticancer drugs. Here, we show that expression of
      recombinant Hsp27 at elevated levels leads to protection of MCF10A human mammary
      epithelial cells from doxorubicin. The protection was associated with suppression
      of the doxorubicin-induced senescence, where Hsp27 inhibited p53-mediated
      induction of p21, the major regulator of the senescence program. Similarly, Hsp27
      inhibited accumulation of p21 and suppressed senescence in response to the p53
      activator nutlin-3, indicating that Hsp27 has a general effect on the p53
      pathway. In line with these findings, down-regulation of Hsp27 in HCT116 human
      colon carcinoma cells that express this heat shock protein at high levels caused
      senescence in a population of cells and sensitized the rest of the cells to
      doxorubicin-induced senescence (at low doses) or apoptosis (at high doses of
      doxorubicin). Induction of senescence by Hsp27 down-regulation associated with
      activation of the p53 pathway and induction of p21. Interestingly, depletion of
      Hsp27 caused neither significant proteotoxic nor genotoxic stress, and therefore
      this heat shock protein seems to have a specific effect on the p53 signaling.
      Indeed, Hsp27 down-regulation was associated with destabilization of HDM2 and
      stabilization of p53. These data suggest that Hsp27 may play a general role in
      regulation of cellular senescence by modulating the p53 pathway.

PMID- 18089809
TI  - Ada3 requirement for HAT recruitment to estrogen receptors and estrogen-dependent
      breast cancer cell proliferation.
AB  - We have previously shown that evolutionarily conserved alteration/deficiency in
      activation (Ada) protein associates with and promotes estrogen receptor (ER)
      mediated target gene expression. Here, we examined the role of endogenous Ada3 to
      recruit histone acetyl transferases (HAT) to an ER-responsive promoter and its
      role in estrogen-dependent cell proliferation and malignant phenotype. Using a
      combination of glycerol gradient cosedimentation and immunoprecipitation
      analyses, we show that Ada3, ER, and three distinct HATs [p300, (p300/CBP
      associated factor) PCAF, and general control nonrepressed 5 (Gcn5)] are present
      in a complex. Using chromatin immunoprecipitation analysis, we show that short
      hairpin RNA (shRNA)-mediated knockdown of Ada3 in ER-positive breast cancer cells
      significantly reduced the ligand-dependent recruitment of p300, PCAF, and Gcn5 to
      the ER-responsive pS2 promoter. Finally, we use shRNA knockdown to show that Ada3
      is critical for estrogen-dependent proliferation of ER-positive breast cancer
      cell lines in two-dimensional, as well as three-dimensional, culture. Knockdown
      of Ada3 in ER-positive MCF-7 cells induced reversion of the transformed phenotype
      in three-dimensional culture. Thus, our results show an important role of Ada3 in
      HAT recruitment to estrogen-responsive target gene promoters and for estrogen
      dependent proliferation of breast cancer cells.

PMID- 18089810
TI  - Inhibition of RAS-mediated transformation and tumorigenesis by targeting the
      downstream E3 ubiquitin ligase seven in absentia homologue.
AB  - Constitutively active RAS small GTPases promote the genesis of human cancers. An
      important goal in cancer biology is to identify means of countervailing activated
      RAS signaling to reverse malignant transformation. Oncogenic K-RAS mutations are
      found in virtually all pancreatic adenocarcinomas, making the RAS pathway an
      ideal target for therapeutic intervention. How to best contravene hyperactivated
      RAS signaling has remained elusive in human pancreatic cancers. Guided by the
      Drosophila studies, we reasoned that a downstream mediator of RAS signals might
      be a suitable anti-RAS target. The E3 ubiquitin ligase seven in absentia (SINA)
      is an essential downstream component of the Drosophila RAS signal transduction
      pathway. Thus, we determined the roles of the conserved human homologues of SINA,
      SIAHs, in mammalian RAS signaling and RAS-mediated tumorigenesis. We report that
      similar to its Drosophila counterpart, human SIAH is also required for oncogenic
      RAS signaling in pancreatic cancer. Inhibiting SIAH-dependent proteolysis blocked
      RAS-mediated focus formation in fibroblasts and abolished the tumor growth of
      human pancreatic cancer cells in soft agar as well as in athymic nude mice. Given
      the high level of conservation of RAS and SIAH function, our study provides
      useful insights into altered proteolysis in the RAS pathway in tumor initiation,
      progression, and oncogenesis. By targeting SIAH, we have found a novel means to
      contravene oncogenic RAS signaling and block RAS-mediated
      transformation/tumorigenesis. Thus, SIAH may offer a novel therapeutic target to
      halt tumor growth and ameliorate RAS-mediated pancreatic cancer.

PMID- 18089811
TI  - Role of tumor necrosis factor-alpha and TRAIL in high-dose radiation-induced
      bystander signaling in lung adenocarcinoma.
AB  - In the present study, ionizing radiation (IR)-induced bystander effects were
      investigated in two lung cancer cell lines. A549 cells were found to be more
      resistant to radiation-conditioned medium (RCM) obtained from A549 cells when
      compared with the H460 exposed to RCM procured from H460 cells. Significant
      release of tumor necrosis factor-alpha (TNF-alpha) was observed in A549 cells
      after IR/RCM exposure, and the survival was reversed with neutralizing antibody
      against TNF-alpha. In H460 cells, significant release of TNF-related apoptosis
      inducing ligand (TRAIL), but not TNF-alpha, was observed in response to IR, RCM
      exposure, or RCM + 2Gy, and neutralizing antibody against TRAIL diminished
      clonogenic inhibition. Mechanistically, TNF-alpha present in RCM of A549 was
      found to mediate nuclear factor-kappaB (NF-kappaB) translocation to nucleus,
      whereas the soluble TRAIL present in RCM of H460 cells mobilized the nuclear
      translocation of PAR-4 (a proapoptotic protein). Analysis of IR-inducible early
      growth response-1 (EGR-1) function showed that EGR-1 was functional in A549 cells
      but not in H460 cells. A significant decrease in RCM-mediated apoptosis was
      observed in both A549 cells stably expressing small interfering RNA EGR-1 and EGR
      1(-/-) mouse embryonic fibroblast cells. Thus, the high-dose IR-induced bystander
      responses in A549 may be dependent on the EGR-1 function and its target gene TNF
      alpha. These findings show that the reduced bystander response in A549 cells is
      due to activation of NF-kappaB signaling by TNF-alpha, whereas enhanced response
      to IR-induced bystander signaling in H460 cells was due to release of TRAIL
      associated with nuclear translocation of PAR-4.

PMID- 18089812
TI  - Biological role and potential therapeutic targeting of the chemokine receptor
      CXCR4 in undifferentiated thyroid cancer.
AB  - Anaplastic thyroid carcinoma (ATC) is a rare thyroid cancer type with an
      extremely poor prognosis. Despite appropriate treatment, which includes surgery,
      radiotherapy, and chemotherapy, this cancer is invariably fatal. CXCR4 is the
      receptor for the stromal cell-derived factor-1 (SDF-1)/CXCL12 chemokine and it is
      expressed in a variety of solid tumors, including papillary thyroid carcinoma.
      Here, we show that ATC cell lines overexpress CXCR4, both at the level of mRNA
      and protein. Furthermore, we found that CXCR4 was overexpressed in ATC clinical
      samples, with respect to normal thyroid tissues by real-time PCR and
      immunohistochemistry. Treatment of ATC cells with SDF-1 induced proliferation and
      increase in phosphorylation of extracellular signal-regulated kinases and protein
      kinase B/AKT. These effects were blocked by the specific CXCR4 antagonist AMD3100
      and by CXCR4 RNA interference. Moreover, AMD3100 effectively reduced tumor growth
      in nude mice inoculated with different ATC cells. Thus, we suggest that CXCR4
      targeting is a novel potential strategy in the treatment of human ATC.

PMID- 18089813
TI  - Recombinant immunoproapoptotic proteins with furin site can translocate and kill
      HER2-positive cancer cells.
AB  - We previously reported the selective killing of HER2-positive tumor cells by a
      class of immunoproapoptotic proteins containing single-chain antibody,
      translocation domain of Pseudomonas exotoxin A (domain II; PEA II), and
      constitutively active human apoptotic molecules. In this study, a novel class of
      antitumor immunoproapoptotic proteins was explored to mediate tumor-specific
      apoptosis both in vitro and in vivo. Three furin cleavage sequences, including a
      synthetic polyarginine tract, and two furin cleavable sequences from PEA and
      diphtheria toxin were respectively used to replace PEA II in the previously
      constructed immunoproapoptotic protein. When produced and secreted by the
      genetically modified Jurkat cells, the novel targeted proapoptotic proteins
      selectively bound to HER2, which is often overexpressed on tumor cell surface.
      Followed by receptor-mediated endocytosis and furin cleavage in the endosome, the
      recombinant proteins could translocate into the cytosol, leading to irreversible
      cell death. Moreover, delivery of these proteins by either i.m. plasmid injection
      or i.v. injection of plasmid-expressing Jurkat cells led to tumor regression and
      prolonged animal survival in a nude mouse xenograft tumor model, indicating in
      vivo antitumor activity of the recombinant proteins. We conclude that the new
      class of immunoproapoptotic proteins show comparable activity with PEA II
      containing counterpart and provide an attractive therapeutic alternative as they
      contain much less exogenous fragments.

PMID- 18089814
TI  - Activation of bone morphogenetic protein signaling by a Gemini vitamin D3
      analogue is mediated by Ras/protein kinase C alpha.
AB  - Bone morphogenetic proteins (BMP) are members of the transforming growth factor
      beta superfamily, and they play an important role for embryonic development, for
      bone and cartilage formation, and during carcinogenesis. We have previously shown
      that the novel Gemini vitamin D(3) analogue, Ro-438-3582 [Ro3582; 1 alpha,25
      dihydroxy-20S,21(3-hydroxy-3-methylbutyl)-23-yne-26,27
      hexafluorocholecalciferol], inhibited cell proliferation and activated the
      BMP/Smad signaling pathway in MCF10AT1 breast epithelial cells. In this report,
      we investigated the upstream signaling pathways responsible for the activation of
      BMP/Smad signaling by Ro3582. Among seven different serine/threonine kinase
      inhibitors that we tested, protein kinase C (PKC) inhibitors blocked the effects
      of Ro3582 on the phosphorylation of Smad1/5, mRNA synthesis for BMP-2 and BMP-6,
      and cell growth in MCF10AT1 cells. Overexpression of PKC alpha, but not PKC
      epsilon, PKC delta or PKC zeta isoforms, increased Ro3582-induced phosphorylation
      of Smad1/5, suggesting that PKC alpha mediates the activation of Smad signaling
      and inhibition of cell proliferation. Interestingly, the activation of Smad
      signaling by Ro3582 was shown in Ha-ras-transfected MCF10AT1 cells, but not in
      the parent cell line (MCF10A without Ras). Inhibiting Ras activity blocked the
      translocation of PKC alpha to the plasma membrane and the phosphorylation of
      Smad1/5 induced by Ro3582, indicating that Ras is necessary for the activation of
      PKC alpha and Smad signaling. In conclusion, Ro3582 inhibits cell proliferation
      and activates BMP/Smad signaling via a Ras and PKC alpha pathway in breast
      epithelial cells.

PMID- 18089815
TI  - Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive
      oxygen species-mediated apoptotic topoisomerase I-DNA cleavable complex formation
      in prostate cancer cells but does not affect the process of cell death.
AB  - The ubiquitious enzyme topoisomerase I can be targeted by drugs which turn these
      enzymes into cellular poisons and subsequently induce cell death. Drugs like
      staurosporine, which do not target topoisomerase I directly, can also lead to
      stabilization of topoisomerase I-DNA cleavable complexes by an indirect process
      of reactive oxygen species (ROS) generation and subsequent oxidative DNA damage.
      In this study, we show that betulinic acid, a catalytic inhibitor of
      topoisomerases, inhibits the formation of apoptotic topoisomerase I-DNA cleavable
      complexes in prostate cancer cells induced by drugs like camptothecin,
      staurosporine, and etoposide. Although events like ROS generation, oxidative DNA
      damage, and DNA fragmentation were observed after betulinic acid treatment, there
      is no topoisomerase I-DNA cleavable complex formation, which is a key step in ROS
      induced apoptotic processes. We have shown that betulinic acid interacts with
      cellular topoisomerase I and prohibits its interaction with the oxidatively
      damaged DNA. Using oligonucleotide containing 8-oxoguanosine modification, we
      have shown that betulinic acid inhibits its cleavage by topoisomerase I in vitro.
      Whereas silencing of topoisomerase I gene by small interfering RNA reduces cell
      death in the case of staurosporine and camptothecin, it cannot substantially
      reduce betulinic acid-induced cell death. Thus, our study provides evidence that
      betulinic acid inhibits formation of apoptotic topoisomerase I-DNA complexes and
      prevents the cellular topoisomerase I from directly participating in the
      apoptotic process.

PMID- 18089817
TI  - Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from
      epidermal growth factor receptor inhibition to the mitochondrion.
AB  - A subset of lung cancers expresses mutant forms of epidermal growth factor
      receptor (EGFR) that are constitutively activated. Cancers bearing activated EGFR
      can be effectively targeted with EGFR inhibitors such as erlotinib. However, the
      death-signaling pathways engaged after EGFR inhibition are poorly understood.
      Here, we show that death after inhibition of EGFR uses the mitochondrial, or
      intrinsic, pathway of cell death controlled by the BCL-2 family of proteins. BCL
      2 inhibits cell death induced by erlotinib, but BCL-2-protected cells are thus
      rendered BCL-2-dependent and sensitive to the BCL-2 antagonist ABT-737. BH3
      profiling reveals that mitochondrial BCL-2 is primed by death signals after EGFR
      inhibition in these cells. As this result implies, key death-signaling proteins
      of the BCL-2 family, including BIM, were found to be up-regulated after erlotinib
      treatment and intercepted by overexpressed BCL-2. BIM is induced by lung cancer
      cell lines that are sensitive to erlotinib but not by those resistant. Reduction
      of BIM by siRNA induces resistance to erlotinib. We show that EGFR activity is
      inhibited by erlotinib in H1650, a lung cancer cell line that bears a sensitizing
      EGFR mutation, but that H1650 is not killed. We identify the block in apoptosis
      in this cell line, and show that a novel form of erlotinib resistance is present,
      a block in BIM up-regulation downstream of EGFR inhibition. This finding has
      clear implications for overcoming resistance to erlotinib. Resistance to EGFR
      inhibition can be modulated by alterations in the intrinsic apoptotic pathway
      controlled by the BCL-2 family of proteins.

PMID- 18089816
TI  - A novel bioluminescent mouse model and effective therapy for adult T-cell
      leukemia/lymphoma.
AB  - Adult T-cell /lymphomaleukemia (ATLL) is caused by human T-cell lymphotropic
      virus type 1 (HTLV-1). Approximately 80% of ATLL patients develop humoral
      hypercalcemia of malignancy (HHM), a life-threatening complication leading to a
      poor prognosis. Parathyroid hormone-related protein (PTHrP) and macrophage
      inflammatory protein-1 alpha (MIP-1 alpha) are important factors in the
      pathogenesis of HHM in ATLL and the expression of PTHrP can be activated by
      nuclear factor kappaB (NF-kappaB). NF-kappaB is constitutively activated in ATLL
      cells and is essential for leukemogenesis including transformation of lymphocytes
      infected by HTLV-1. Our goal was to evaluate the effects of NF-kappaB disruption
      by a proteasomal inhibitor (PS-341) and osteoclastic inhibition by zoledronic
      acid (Zol) on the development of ATLL and HHM using a novel bioluminescent mouse
      model. We found that PS-341 decreased cell viability, increased apoptosis, and
      down-regulated PTHrP expression in ATLL cells in vitro. To investigate the in
      vivo efficacy, nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice
      were xenografted with ATLL cells and treated with vehicle control, PS-341, Zol,
      or a combination of PS-341 and Zol. Bioluminescent imaging and tumor cell count
      showed a significant reduction in tumor burden in mice from all treatment groups.
      All treatments also significantly reduced the plasma calcium concentrations. Zol
      treatment increased trabecular bone volume and decreased osteoclast parameters.
      PS-341 reduced PTHrP and MIP-1 alpha expression in tumor cells in vivo. Our
      results indicate that both PS-341 and Zol are effective treatments for ATLL and
      HHM, which are refractory to conventional therapy.

PMID- 18089818
TI  - Oncogenic BARD1 isoforms expressed in gynecological cancers.
AB  - BARD1 is required for protein stability and tumor suppressor functions of BRCA1,
      which depend on the ubiquitin ligase activity of the BRCA1-BARD1 heterodimer. The
      NH(2)-terminal RING domains of both proteins act as interaction modules and form
      a ubiquitin ligase, which has functions in DNA repair, cell cycle checkpoint
      regulation, and mitosis. Interestingly, up-regulated expression of truncated
      BARD1 isoforms was found to be associated with poor prognosis in breast and
      ovarian cancers and, in a hormonally regulated fashion, in the human
      cytotrophoblast, a cell type with properties reminiscent of cancer cells. We
      therefore performed reverse transcription-PCR to determine the structure of BARD1
      isoforms in cell lines derived from hormone-dependent and hormone-independent
      cancers. We found a specific combination of isoforms, generated by differential
      splicing and alternative transcription initiation, mostly lacking the BRCA1
      interaction domain, in gynecologic but not hematologic cancer cell lines. To
      investigate the prevalence of BARD1 isoforms in tumors, we applied
      immunohistochemistry to ovarian cancers, using antibodies distinguishing full
      length BARD1 and isoforms. Expression of NH(2) terminally truncated BARD1 was
      correlated with advanced stage of cancer, and expression of spliced isoforms was
      typical for clear cell carcinoma, the ovarian cancer with worst prognosis,
      suggesting a role of BARD1 isoforms in cancer progression. To challenge this
      hypothesis, we silenced BARD1 isoforms in ovarian cancer cells that lacked wild
      type BARD1 by siRNA interference, which led to a complete proliferation arrest.
      Thus, BARD1 isoform expression is required for cancer cell proliferation, which
      is compatible with the notion that BARD1 isoforms act as cancer maintenance
      genes.

PMID- 18089819
TI  - Differential sensitivity of malignant glioma cells to methylating and
      chloroethylating anticancer drugs: p53 determines the switch by regulating xpc,
      ddb2, and DNA double-strand breaks.
AB  - Glioblastoma multiforme is the most severe form of brain cancer. First line
      therapy includes the methylating agent temozolomide and/or the chloroethylating
      nitrosoureas [1-(2-chloroethyl)-1-nitrosourea; CNU] nimustine [1-(4-amino-2
      methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea; ACNU], carmustine
      [1,3-bis(2-chloroethyl)-1-nitrosourea; BCNU], or lomustine [1-(2-chloroethyl)-3
      cyclohexyl-1-nitrosourea; CCNU]. The mechanism of cell death after CNU treatment
      is largely unknown. Here we show that ACNU and BCNU induce apoptosis in U87MG
      [p53 wild-type (p53wt)] and U138MG [p53 mutant (p53mt)] glioma cells. However,
      contrary to what we observed previously for temozolomide, chloroethylating drugs
      are more toxic for p53-mutated glioma cells and induce both apoptosis and
      necrosis. Inactivation of p53 by pifithrin-alpha or siRNA down-regulation
      sensitized p53wt but not p53mt glioma cells to ACNU and BCNU. ACNU and BCNU
      provoke the formation of DNA double-strand breaks (DSB) in glioma cells that
      precede the onset of apoptosis and necrosis. Although these DSBs are repaired in
      p53wt cells, they accumulate in p53mt cells. Therefore, functional p53 seems to
      stimulate the repair of CNU-induced cross-links and/or DSBs generated from CNU
      induced lesions. Expression analysis revealed an up-regulation of xpc and ddb2
      mRNA in response to ACNU in U87MG but not U138MG cells, indicating p53 regulates
      a pathway that involves these DNA repair proteins. ACNU-induced apoptosis in
      p53wt glioma cells is executed via both the extrinsic and intrinsic apoptotic
      pathway, whereas in p53mt glioma cells, the mitochondrial pathway becomes
      activated. The data suggest that p53 has opposing effects in gliomas treated with
      methylating or chloroethylating agents and, therefore, the p53 status should be
      taken into account when deciding which therapeutic drug to use.

PMID- 18089820
TI  - Predicting response to radioimmunotherapy from the tumor microenvironment of
      colorectal carcinomas.
AB  - Solid tumors have a heterogeneous pathophysiology, which directly affects
      antibody-targeted therapies. Here, we consider the influence of selected tumor
      parameters on radioimmunotherapy, by comparing the gross biodistribution,
      microdistribution, and therapeutic efficacy of either radiolabeled or
      fluorescently labeled antibodies (A5B7 anti-carcinoembryonic antigen antibody and
      a nonspecific control) after i.v. injection in two contrasting human colorectal
      xenografts in MF1 nude mice. The LS174T is moderately/poorly differentiated,
      whereas SW1222 has a well-differentiated glandular structure. Biodistribution
      studies (1.8 MBq (131)I-labeled A5B7, four mice per group) showed similar gross
      tumor uptake at 48 h in the two models (25.1% and 24.0% injected dose per gram,
      respectively). However, in therapy studies (six mice per group), LS174T required
      a 3-fold increase in dose (18 versus 6 MBq) to equal SW1222 growth inhibition (
      approximately 55 versus approximately 60 days, respectively). To investigate the
      basis of this discrepancy, high-resolution multifluorescence microscopy was used
      to study antibody localization in relation to tumor parameters (5 min, 1 and 24
      h, four mice per time point). Three-dimensional microvascular corrosion casting
      and transmission electron microscopy showed further structural differences
      between xenografts. Vascular supply, overall antigen distribution, and tumor
      structure varied greatly between models, and were principally responsible for
      major differences in antibody localization and subsequent therapeutic efficacy.
      The study shows that multiparameter, high-resolution imaging of both therapeutic
      and tumor microenvironment is required to comprehend complex antibody-tumor
      interactions, and to determine which tumor regions are being successfully
      treated. This will inform the design of optimized clinical trials of single and
      combined agents, and aid individual patient selection for antibody-targeted
      therapies.

PMID- 18089821
TI  - Vitamin E analogues inhibit angiogenesis by selective induction of apoptosis in
      proliferating endothelial cells: the role of oxidative stress.
AB  - "Mitocans" from the vitamin E group of selective anticancer drugs, alpha
      tocopheryl succinate (alpha-TOS) and its ether analogue alpha-TEA, triggered
      apoptosis in proliferating but not arrested endothelial cells. Angiogenic
      endothelial cells exposed to the vitamin E analogues, unlike their arrested
      counterparts, readily accumulated reactive oxygen species (ROS) by interfering
      with the mitochondrial redox chain and activating the intrinsic apoptotic
      pathway. The vitamin E analogues inhibited angiogenesis in vitro as assessed
      using the "wound-healing" and "tube-forming" models. Endothelial cells deficient
      in mitochondrial DNA (mtDNA) were resistant to the vitamin E analogues, both in
      ROS accumulation and apoptosis induction, maintaining their angiogenic potential.
      alpha-TOS inhibited angiogenesis in a mouse cancer model, as documented by
      ultrasound imaging. We conclude that vitamin E analogues selectively kill
      angiogenic endothelial cells, suppressing tumor growth, which has intriguing
      clinical implications.

PMID- 18089822
TI  - Induction of apoptosis in plasma cells by B lymphocyte-induced maturation protein
      1 knockdown.
AB  - B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional
      repressor that plays an important role during plasmacytic differentiation and is
      expressed in normal and transformed plasma cells. We here investigated the
      importance of continuous Blimp-1 expression. We found that knockdown of Blimp-1
      expression by lentiviral vector-delivered short hairpin RNA causes apoptosis in
      multiple myeloma cell lines and plasmacytoma cells, indicating that continued
      expression of Blimp-1 is required for cell survival. We examined the mechanism
      underlying Blimp-1 knockdown-mediated apoptosis and found that the Blimp-1
      knockdown neither reversed the phenotypic markers of plasma cells nor caused cell
      cycle arrest. Instead, our results show that knockdown of Blimp-1 induced the
      proapoptotic protein Bim, reduced the antiapoptotic protein Mcl-1, and activated
      caspase-9 and caspase-3. We further link apoptosis in transformed plasma cells
      mediated by proteasome inhibitors, the effective therapeutic agent for multiple
      myeloma patients, with reduced expression of Blimp-1. Lastly, we show that Blimp
      1-dependent cell survival may act downstream of IFN regulatory factor 4 (IRF4)
      because IRF4 knockdown leads to down-regulation of Blimp-1 and apoptosis in
      multiple myeloma cells and plasmacytoma cells. Together, our data suggest that
      Blimp-1 ensures the survival of transformed plasma cells.

PMID- 18089823
TI  - PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer
      models with EGFR and ERBB2 mutations that are resistant to gefitinib.
AB  - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and
      erlotinib are effective treatments for a subset of non-small cell lung cancers.
      In particular, cancers with specific EGFR-activating mutations seem to be the
      most sensitive to these agents. However, despite their initial response, such
      cancers almost invariably develop resistance. In 50% of such cancers, a secondary
      EGFR mutation, T790M, has been identified that renders gefitinib and erlotinib
      ineffective inhibitors of EGFR kinase activity. Thus, there is a clinical need to
      develop novel EGFR inhibitors that can effectively inactivate T790M-containing
      EGFR proteins. In this study, we evaluate the effectiveness of a novel compound,
      PF00299804, an irreversible pan-ERBB inhibitor. The results from these studies
      show that PF00299804 is a potent inhibitor of EGFR-activating mutations as well
      as the EGFR T790M resistance mutation both in vitro and in vivo. Additionally,
      PF00299804 is a highly effective inhibitor of both the wild-type ERBB2 and the
      gefitinib-resistant oncogenic ERBB2 mutation identified in lung cancers. These
      preclinical evaluations support further clinical development of PF00299804 for
      cancers with mutations and/or amplifications of ERBB family members.

PMID- 18089824
TI  - ERK-dependent MKP-1-mediated cisplatin resistance in human ovarian cancer cells.
AB  - Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is the MAPK
      phosphatase family member that negatively regulates MAPK signaling. Our previous
      study showed that MKP-1 is involved in cisplatin resistance, but the mechanism
      underlying its resistance is not understood. Here, we show that ERK2-mediated MKP
      1 expression is critical for cisplatin resistance. Specifically, we showed that
      in the human ovarian cancer cell lines, cisplatin induces MKP-1 through
      phosphorylation. We also showed that inhibition of ERK2 activity by the MEK1/2
      inhibitor U0126 or by small interfering RNA silencing decreases MKP-1 induction,
      leading to an increase in cisplatin-induced cell death, which mimicked the
      results obtained with cells in which MKP-1 is down-regulated. Importantly, down
      regulation of ERK2 decreased cisplatin-induced MKP-1 phosphorylation, suggesting
      that MKP-1 phosphorylation depends on ERK2 activity. Furthermore, down-regulation
      of ERK2 or MKP-1 enhanced cisplatin-induced apoptosis. In addition, we showed
      that down-regulation of ERK2 or MKP-1 decreases the basal level of Bcl-2 protein
      and that inhibition of Bcl-2 activity sensitizes ovarian cancer cells to
      cisplatin. Collectively, our results indicate that induction of MKP-1 by
      cisplatin is through phosphorylation involving ERK signaling and that MKP-1 plays
      a critical role in ERK-mediated cisplatin resistance. Thus, our results suggest
      that targeting ERK-MKP-1 signaling could overcome cisplatin resistance in human
      ovarian cancer.

PMID- 18089825
TI  - Targeting Cdc37 inhibits multiple signaling pathways and induces growth arrest in
      prostate cancer cells.
AB  - Members of the 90-kDa heat shock protein (HSP90) family are known to bind and
      stabilize intermediates in a wide variety of cell signaling pathways and
      contribute to their dysregulation in cancer. An important intracellular cofactor
      for HSP90 is Cdc37, a protein with a broad role in fostering the activities of
      protein kinases. By targeting Cdc37 using RNA interference, we have shown that
      the loss of Cdc37 function induces irreversible growth arrest in androgen
      receptor-positive and -negative prostate carcinoma cells. In contrast to HSP90
      directed agents, Cdc37 targeting seems to affect cancer cells through a distinct
      mechanism and does not significantly deplete the intracellular levels of most
      known HSP90 client proteins. Instead, Cdc37 depletion inhibits cellular kinase
      activity and flux through growth-promoting signal transduction cascades. We show
      that the loss of Cdc37 leads to reduced activity of the Erk, Akt, mTOR, and
      androgen-induced pathways. We have also discovered synergistic interactions
      between Cdc37 inactivation and the HSP90-inhibitory anticancer drug 17
      (allylamino)-17-demethoxygeldanamycin (17AAG). These interactions involve
      enhanced degradation of proteins essential for growth and inhibition of 17AAG
      induced expression of the antiapoptotic HSP70. Thus, Cdc37 is essential for
      maintaining prostate tumor cell growth and may represent a novel target in the
      search for multitargeted therapies based on the HSP90 chaperone system.

PMID- 18089826
TI  - Control of ocular tumor growth and metastatic spread by soluble and membrane Fas
      ligand.
AB  - Fas ligand (FasL) can be either membrane bound, or cleaved by metalloproteinases
      (MMP) to produce a soluble protein. The two different forms of FasL are reported
      to have opposite functions-membrane-bound FasL (mFasL) is proinflammatory and
      soluble FasL (sFasL) is antiinflammatory. We previously showed that, within the
      immune-privileged eye, tumors expressing high levels of mFasL overcame the
      suppressive ocular environment, triggered an inflammatory response, and were
      subsequently rejected. By contrast, eye tumors expressing low levels of mFasL
      grew progressively. To evaluate the effect of sFasL on the tumor growth and
      metastatic potential of ocular FasL-expressing tumors, we compared tumor cell
      clones that expressed equal amounts of (low) mFasL in the presence or absence of
      sFasL. Tumor cells transfected with a modified FasL gene expressed only mFasL
      (noncleavable), grew progressively within the eye, and induced systemic
      protective immunity that prevented metastatic spread of tumor cells to the liver.
      Unexpectedly, tumors transfected with wild-type FasL (wtFasL; cleavable), which
      could produce both sFasL and mFasL, elicited considerably more inflammation and
      grew more slowly within the eye. However, the cleavable wtFasL eye tumors failed
      to trigger protective immunity and gave rise to liver metastases. Interestingly,
      exposure to the ocular environment was required for the wtFasL tumors to gain
      metastatic potential. We conclude that the fate of FasL-expressing tumors is
      determined by a combination of the following: (a) the relative proportion of
      membrane and sFasL, and (b) the local environment that determines the extent of
      FasL cleavage.

PMID- 18089827
TI  - In vivo imaging and quantitation of adoptively transferred human antigen-specific
      T cells transduced to express a human norepinephrine transporter gene.
AB  - Sequential imaging of genetically marked effector cells after adoptive transfer
      in vivo has greatly enhanced analyses of their biodistribution, growth, and
      activity both in animal models and in clinical trials of cellular immunotherapy.
      However, the immunogenicity of cells expressing xenogeneic reporter constructs
      limits their survival and clinical utility. To address this limitation, we have
      evaluated a human norepinephrine transporter (hNET) permitting imaging of
      transduced cells in vivo with a previously approved clinical grade radiolabeled
      probe, metaiodobenzylguanidine (MIBG). The hNET gene cDNA was cloned from the SK
      N-SH cell line and inserted into a bicistronic retroviral vector also encoding
      green fluorescent protein. Following transfection, human EBV-specific T
      lymphocytes seemed fully functional in vitro and also selectively accumulated
      [(123)I]MIBG. In nonobese diabetic/severe combined immunodeficient mice bearing
      human EBV lymphoma xenografts, as few as 10(4) transduced T cells injected into
      the tumors could be imaged by single-photon emission computed tomography (SPECT)
      or positron emission tomography (PET) after i.v. infusion of [(123)I]MIBG or
      [(124)I]MIBG, respectively. When hNET(+) EBV-specific T cells were infused i.v.,
      their migration and specific accumulation in EBV(+) tumors expressing their
      restricting HLA allele could be imaged by SPECT or PET over 28 days. Image
      intensity was closely correlated with the number of T cells accumulated in
      targeted tumors. The use of two reporter probes (MIBG and 2'-deoxy-2'-fluoro-beta
      d-arabinofuranosyl-5-iodouracil) permitted independent contemporaneous tracking
      of two distinct EBV-specific T-cell subpopulations expressing different reporter
      genes (hNET-CD4(+) T cells and HSV-TK-CD8(+) T cells) in the same animal using
      three-dimensional nuclear modalities (SPECT and PET). The hNET-based system
      described may thus have significant potential as a nonimmunogenic reporter for
      extended repeated quantitative in vivo imaging of transduced cells in man.

PMID- 18089828
TI  - Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy
      for metastatic prostate cancer.
AB  - A close connectivity between autoimmune and tumor rejection responses is known to
      exist in the case of melanoma immunotherapy. However, relatively little is known
      about self-antigens on other types of normal cells, their relation to the
      development of autoimmune disease, and their possible coexistence as potential
      tumor rejection antigens on associated tumors. In the current study, we induced
      inflammatory killing of normal prostate tissue in situ using a fusogenic membrane
      glycoprotein along with the immune adjuvant hsp70. We show here that, in the
      prostate, hsp70 induces interleukin (IL)-6, which triggers a CD4- and CD8
      dependent progressive autoimmune reactivity, associated with IL-17 expression.
      This autoimmune response was also able to induce the rejection of established
      prostate tumors, but not other histologic types of tumors, growing elsewhere in
      the animal. These data show that the intimate connectivity between autoimmune and
      tumor rejection responses extends beyond the classic melanoma paradigm and may be
      clinically valuable for the treatment of established metastatic disease of the
      prostate.

PMID- 18089829
TI  - Activation of tumor-specific CD8+ T Cells after intratumoral Ad5-TRAIL/CpG
      oligodeoxynucleotide combination therapy.
AB  - CD8(+) T-cell activation via cross-presentation of antigens from apoptotic tumor
      cells is controversial. Dendritic cells capture naturally shed tumor antigens and
      cross-present them to CD8(+) T cells; unfortunately, the frequency of activated
      CD8(+) T cells is often too low to mount an effective response against the tumor.
      By increasing the amount of antigen for presentation, a larger T-cell response
      can be theoretically elicited. We used a recombinant adenovirus encoding full
      length murine tumor necrosis factor-related apoptosis-inducing ligand (Ad5
      mTRAIL) to induce tumor cell apoptosis, and when given intratumorally to mice
      bearing experimental renal cell carcinoma (Renca) tumors, Ad5-mTRAIL minimally
      prolonged survival and induced a low level of CTL activity. To enhance dendritic
      cell efficiency, an immunostimulatory CpG oligodeoxynucleotide (CpG ODN) was
      combined with Ad5-mTRAIL. This combination therapy significantly augmented in
      vivo antigen-specific T-cell proliferation and CTL activity, as well as prolonged
      survival of Renca tumor-bearing mice. Interestingly, depletion of CD4(+) or
      CD25(+) cells before therapy further enhanced survival and in vivo CTL activity.
      In addition, tumor-free mice depleted of CD4(+) cells were also able to reject a
      subsequent challenge of Renca cells, but not MHC-matched RM-11 prostate tumor
      cells, demonstrating the existence of immunologic memory. These results
      collectively show that local treatment with Ad5-mTRAIL and CpG ODN can augment
      tumor antigen cross-presentation resulting in T-cell proliferation, enhanced CTL
      activity, and increased animal survival.

PMID- 18089830
TI  - Elements related to heterogeneity of antibody-dependent cell cytotoxicity in
      patients under trastuzumab therapy for primary operable breast cancer
      overexpressing Her2.
AB  - Preliminary results from a pilot trial on trastuzumab's mechanism of action
      against operable breast tumors overexpressing Her2 suggested a role for antibody
      dependent cell cytotoxicity (ADCC). To examine factors affecting ADCC intensity
      and variability, we extended this study to the phenotypic and functional analysis
      of circulating mononuclear cells in 18 patients. ADCC was induced by trastuzumab
      therapy in 15 of 18 patients (83%). Inability to develop ADCC in three patients
      did not depend on inadequate levels of trastuzumab because further increase in
      its concentration in vitro was ineffective. Rather, susceptibility to develop
      ADCC was fairly predicted by test with trastuzumab before therapy and was
      correlated to the number of lymphocytes coexpressing CD16 and CD56. Phenotypic
      analysis at the end of ADCC evaluating down-regulation of CD16, and up-regulation
      of CD69 and CD107a, confirmed that natural killer (NK) cells and CD56(+) T cells
      were involved in productive engagement of trastuzumab. Also, the killing
      efficiency of CD16(+) lymphocytes was influenced by 158 V/F polymorphism of Fc
      gamma RIII (CD16), whereas variations of CD247 on NK cells were consistent with
      trends between ADCC before and after therapy. Complete pathologic response was
      observed in one patient showing ADCC of outstanding intensity, whereas four cases
      of partial response showed intermediate ADCC; none of the three patients unable
      to mount ADCC had significant tumor regression. These data indicate that quantity
      and lytic efficiency of CD16(+) lymphocytes are major factors for ADCC induction
      by trastuzumab, and confirm that breast cancer responses to short-term
      trastuzumab monotherapy may depend on involvement of the ADCC mechanism.

PMID- 18089831
TI  - Identification of 14-3-3 theta as an antigen that induces a humoral response in
      lung cancer.
AB  - We have implemented a strategy to identify tumor antigens that induce a humoral
      immune response in lung cancer based on the analysis of tumor cell proteins.
      Chromatographically fractionated protein extracts from three lung cancer cell
      lines were subjected to Western blotting and hybridization with individual sera
      to determine serum antibody binding. Two sets of sera were initially
      investigated. One set consisted of sera from 19 newly diagnosed subjects with
      lung adenocarcinoma and 19 matched controls. A second independent set consisted
      of sera from 26 newly diagnosed subjects with lung adenocarcinoma and 24 controls
      matched for age, gender, and smoking history. One protein that exhibited
      significant reactivity with both sets of cancer sera (P = 0.0008) was confidently
      identified by mass spectrometry as 14-3-3 theta. Remarkably, significant
      autoantibody reactivity against 14-3-3 theta was also observed in an analysis of
      a third set consisting of 18 prediagnostic lung cancer sera collected as part of
      the Beta-Carotene and Retinol Efficacy Trial cohort study, relative to 19 matched
      controls (P = 0.0042). A receiver operating characteristic curve constructed with
      a panel of three proteins consisting of 14-3-3 theta identified in this study,
      plus annexin 1 and protein gene product 9.5 proteins previously identified as
      associated with autoantibodies in lung cancer, gave a sensitivity of 55% at 95%
      specificity (area under the curve, 0.838) in discriminating lung cancer at the
      preclinical stage from matched controls.

PMID- 18089832
TI  - Molecular mechanisms of resveratrol action in lung cancer cells using dual
      protein and microarray analyses.
AB  - Resveratrol, a natural phytoestrogen found in red wine and a variety of plants,
      is reported to have protective effects against lung cancer; however, there is
      little work directed toward the understanding of the mechanism of its action in
      this disease. In this study, we used a combination of experimental approaches to
      understand the biological activity and molecular mechanisms of resveratrol.
      Microarray gene expression profiling and high-throughput immunoblotting
      (PowerBlot) methodologies were employed to gain insights into the molecular
      mechanisms of resveratrol action in human lung cancer cells. In this report, we
      confirm the up-regulation of p53 and p21 and the induction of apoptosis by the
      activation of the caspases and the disruption of the mitochondrial membrane
      complex. We show the arrest of A549 cells in the G(1) phase of cell cycle in the
      presence of resveratrol and also report alterations in both gene and protein
      expressions of cyclin A, chk1, CDC27, and Eg5. Furthermore, the results indicated
      that resveratrol action is mediated via the transforming growth factor-beta
      pathway, particularly through the Smad proteins. Results showed the down
      regulation of the Smad activators 2 and 4 and the up-regulation of the repressor
      Smad 7 as a result of resveratrol treatment. Resveratrol is a potent inhibitor of
      A549 lung cancer cell growth, and our results suggest that resveratrol may be a
      promising chemopreventive or chemotherapeutic agent for lung cancer.

PMID- 18089833
TI  - Effects of dietary energy restriction on gene regulation in mammary epithelial
      cells.
AB  - The objective of this study was to determine whether dietary energy restriction
      (DER) affects the pattern of gene expression in three interrelated energy
      metabolism pathways: glycolysis, gluconeogenesis, and the citric acid cycle.
      Mammary carcinogenesis was initiated by the i.p. injection of female Sprague
      Dawley rats with 50 mg of 1-methyl-1-nitrosourea per kilogram of body weight.
      Five days following 1-methyl-1-nitrosourea administration, animals were fed ad
      libitum or 80% or 60% of the ad libitum intake. Epithelial cells were harvested
      from histologically confirmed adenocarcinomas (adenocarcinoma epithelial cell;
      ACEC) and uninvolved mammary gland (mammary gland epithelial cells; MGEC) via
      laser capture microdissection, whereas isolated RNA was arrayed on Affymetrix
      R230 2.0 genome chips. Principal components analysis revealed complete separation
      of the patterns of gene expression between ACEC versus MGEC. Further examination
      of the data set revealed an up-regulated pattern of expression in the ACEC of
      genes involved in glycolysis, whereas gluconeogenesis was suppressed. In general,
      genes involved in the citric acid cycle were not differentially expressed;
      however, pyruvate dehydrogenase expression was down-regulated and lactate
      dehydrogenase expression was increased in ACEC versus MGEC. Collectively, the
      observed patterns of expression were consistent with the Warburg effect. DER
      exerted no effect on the Warburg pattern of gene expression or on other aspects
      of these energy metabolism pathways. These findings imply that efforts to target
      the Warburg effect for cancer prevention are mechanistically distinct from those
      modulated by DER and provide a rationale for the combination of approaches that
      target basic defects in energy metabolism and energy-sensing pathways for the
      prevention of breast cancer.

PMID- 18089834
TI  - Ataxia telangiectasia-mutated and p53 are potential mediators of chloroquine
      induced resistance to mammary carcinogenesis.
AB  - The use of agents to prevent the onset of and/or the progression to breast cancer
      has the potential to lower breast cancer risk. We have previously shown that the
      tumor-suppressor gene p53 is a potential mediator of hormone
      (estrogen/progesterone)-induced protection against chemical carcinogen-induced
      mammary carcinogenesis in animal models. Here, we show for the first time a
      breast cancer-protective effect of chloroquine in an animal model. Chloroquine
      significantly reduced the incidence of N-methyl-N-nitrosourea-induced mammary
      tumors in our animal model similar to estrogen/progesterone treatment. No
      protection was seen in our BALB/c p53-null mammary epithelium model, indicating a
      p53 dependency for the chloroquine effect. Using a human nontumorigenic mammary
      gland epithelial cell line, MCF10A, we confirm that in the absence of detectable
      DNA damage, chloroquine activates the tumor-suppressor p53 and the p53 downstream
      target gene p21, resulting in G(1) cell cycle arrest. p53 activation occurs at a
      posttranslational level via chloroquine-dependent phosphorylation of the
      checkpoint protein kinase, ataxia telangiectasia-mutated (ATM), leading to ATM
      dependent phosphorylation of p53. In primary mammary gland epithelial cells
      isolated from p53-null mice, chloroquine does not induce G(1) cell cycle arrest
      compared with cells isolated from wild-type mice, also indicating a p53
      dependency. Our results indicate that a short prior exposure to chloroquine may
      have a preventative application for mammary carcinogenesis.

PMID- 18089836
TI  - A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1
      c)quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening
      with drug-immobilized affinity beads.
AB  - 6-((2-(Dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)-quinolin-7-one
      dihydrochloride (TAS-103) is a quinoline derivative that displays antitumor
      activity in murine and human tumor models. TAS-103 has been reported to be a
      potent topoisomerase II poison. However, other studies have indicated that
      cellular susceptibility to TAS-103 is not correlated with topoisomerase II
      expression. Because the direct target of TAS-103 remained unclear, we searched
      for a TAS-103 binding protein using high-performance affinity latex beads. We
      obtained a component of the signal recognition particle (SRP) as a TAS-103
      binding protein. This component is a 54-kDa subunit (SRP54) of SRP, which
      mediates the proper delivery of secretory proteins in cells. We fractioned 293T
      cell lysates using gel-filtration chromatography and performed a
      coimmunoprecipitation assay using 293T cells expressing FLAG-tagged SRP54. The
      results revealed that TAS-103 disrupts SRP complex formation and reduces the
      amount of SRP14 and SRP19. TAS-103 treatment and RNAi-mediated knockdown of SRP54
      or SRP14 promoted accumulation of the exogenously expressed chimeric protein
      interleukin-6-FLAG inside cells. In conclusion, we identified signal recognition
      particle as a target of TAS-103 by using affinity latex beads. This provides new
      insights into the mechanism underlying the effects of chemotherapies comprising
      TAS-103 and demonstrates the usefulness of the affinity beads.

PMID- 18089837
TI  - N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide (ICA-27243): a novel, selective
      KCNQ2/Q3 potassium channel activator.
AB  - KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) are voltage-gated K(+) channel subunits that
      underlie the neuronal M current. In humans, mutations in these genes lead to a
      rare form of neonatal epilepsy (Biervert et al., 1998; Singh et al., 1998),
      suggesting that KCNQ2/Q3 channels may be attractive targets for novel
      antiepileptic drugs. In the present study, we have identified the compound N-(6
      chloro-pyridin-3-yl)-3,4-difluoro-benzamide (ICA-27243) as a selective activator
      of the neuronal M current and KCNQ2/Q3 channels. In SH-SY5Y human neuroblastoma
      cells, ICA-27243 produced membrane potential hyperpolarization that could be
      prevented by coadministration with the M-current inhibitors 10,10-bis(4
      pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE-991) and linopirdine.
      ICA-27243 enhanced both (86)Rb(+) efflux (EC(50) = 0.2 microM) and whole-cell
      currents in Chinese hamster ovary cells stably expressing heteromultimeric
      KCNQ2/Q3 channels (EC(50) = 0.4 microM). Activation of KCNQ2/Q3 channels was
      associated with a hyperpolarizing shift of the voltage dependence of channel
      activation (V((1/2)) shift of -19 mV at 10 microM). In contrast, ICA-27243 was
      less effective at activating KCNQ4 and KCNQ3/Q5 and was selective over a wide
      range of neurotransmitter receptors and ion channels such as voltage-dependent
      sodium channels and GABA-gated chloride channels. ICA-27243 (1-10 microM) was
      found to reversibly suppress seizure-like activity in an ex vivo hippocampal
      slice model of epilepsy and demonstrated in vivo anticonvulsant activity (ED(50)
      = 8.4 mg/kg) in the mouse maximal electroshock epilepsy model. In conclusion, ICA
      27243 represents the first member of a novel chemical class of selective KCNQ2/Q3
      activators with anticonvulsant-like activity in experimental models of epilepsy.

PMID- 18089838
TI  - Dioxin-mediated up-regulation of aryl hydrocarbon receptor target genes is
      dependent on the calcium/calmodulin/CaMKIalpha pathway.
AB  - Regulation of genes targeted by the ligand-activated aryl hydrocarbon receptor
      (AhR) has been shown to be controlled by calcium (Ca(2+)) changes induced by AhR
      agonists such as the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD). The present study was designed to characterize this link between
      Ca(2+) and the AhR pathway. We report that fast elevation of intracellular Ca(2+)
      in TCDD-exposed mammary MCF-7 cells was associated with transient enhanced
      activity of the Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaMK) pathway.
      Chemical inhibition of this pathway using the CaM antagonist W7 or the CaMK
      inhibitor KN-93 strongly reduced TCDD-mediated induction of the AhR target gene
      CYP1A1. Small interfering RNA (siRNA)-mediated knockdown expression of
      CaMKIalpha, one of the CaMK isoforms, similarly prevented CYP1A1 up-regulation.
      Both KN-93 and siRNA targeting CaMKIalpha were found to abolish TCDD-mediated
      activation of CYP1A1 promoter and TCDD-triggered nuclear import of AhR, a crucial
      step of the AhR signaling pathway. TCDD-mediated inductions of various AhR
      targets, such as the drug metabolizing CYP1B1, the cytokine interleukin-1beta,
      the chemokines interleukin-8 and CCL1, the adhesion molecule beta7 integrin, and
      the AhR repressor, were also prevented by KN-93 in human macrophages. Taken
      together, these data identified the Ca(2+)/CaM/CaMKIalpha pathway as an important
      contributing factor to AhR-mediated genomic response.

PMID- 18089839
TI  - Direct role of streptozotocin in inducing thermal hyperalgesia by enhanced
      expression of transient receptor potential vanilloid 1 in sensory neurons.
AB  - Streptozotocin (STZ) is a diabetogenic agent extensively used to induce diabetes
      and to study complications including diabetic peripheral neuropathy (DPN). While
      studying the influence of transient receptor potential vanilloid 1 (TRPV1) on DPN
      in the STZ-induced diabetic mouse model, we found that a proportion of STZ
      treated mice was nondiabetic but still exhibited hyperalgesia. To understand the
      mechanism underlying this phenomenon, dorsal root ganglion (DRG) neurons and
      stably TRPV1 expressing human embryonic kidney (HEK) 293T cells were used to
      study the expression and function of TRPV1. Incubation of DRG neurons with STZ
      resulted in a significant increase in the amplitude of capsaicin-induced TRPV1
      mediated current and Ca(2+) influx compared with vehicle-treated sister cultures.
      It was also found that STZ treatment induced higher levels of reactive oxygen
      species, which was abolished with concomitant treatment with catalase. Treatment
      of cells with H(2)O(2) mimicked the effects of STZ. Western blot analysis
      revealed an increase in TRPV1 protein content and phospho p38 (p-p38) mitogen
      activated protein kinase (MAPK) levels in DRG of STZ-injected diabetic and
      nondiabetic hyperalgesic mice compared with control mice. Furthermore, in stably
      TRPV1-expressing HEK 293T cells, STZ treatment induced an increase in TRPV1
      protein content and p-p38 MAPK levels, which was abolished with concomitant
      treatment with catalase or p38 MAPK inhibitor. These results reveal that STZ has
      a direct action on neurons and modulates the expression and function of TRPV1, a
      nociceptive ion channel that is responsible for inflammatory thermal pain.

PMID- 18089840
TI  - A selective Nav1.8 sodium channel blocker, A-803467 [5-(4-chlorophenyl-N-(3,5
      dimethoxyphenyl)furan-2-carboxamide], attenuates spinal neuronal activity in
      neuropathic rats.
AB  - We have recently reported that systemic delivery of A-803467 [5-(4-chlorophenyl-N
      (3,5-dimethoxyphenyl)furan-2-carboxamide], a selective Na(v)1.8 sodium channel
      blocker, reduces behavioral measures of chronic pain. In the current study, the
      effects of A-803467 on evoked and spontaneous firing of wide dynamic range (WDR)
      neurons were measured in uninjured and rats with spinal nerve ligations (SNLs).
      Administration of A-803467 (10-30 mg/kg i.v.) reduced mechanically evoked (10-g
      von Frey hair) and spontaneous WDR neuronal activity in SNL rats. In uninjured
      rats, A-803467 (20 mg/kg i.v.) transiently reduced evoked but not spontaneous
      firing of WDR neurons. The systemic effects of A-803467 in SNL rats were not
      altered by spinal transection or by systemic pretreatment with the transient
      receptor potential vanilloid type 1 (TRPV1) receptor agonist, resiniferatoxin, at
      doses that impair the function of TRPV1-expressing fibers. To determine sites of
      action, A-803467 was administered into spinal tissue, into the uninjured L4
      dorsal root ganglion (DRG), or into the neuronal receptive field. Injections of A
      803467 into the L4 DRG (30-100 nmol/1 mul) or into the hindpaw receptive field
      (300 nmol/50 mul) reduced evoked but not spontaneous WDR firing. In contrast,
      intraspinal (50-150 nmol/0.5 mul) injection of A-803467 decreased both evoked and
      spontaneous discharges of WDR neurons. Thus, Na(v)1.8 sodium channels on the cell
      bodies/axons within the L4 DRG as well as on peripheral and central terminals of
      primary afferent neurons regulate the inflow of low-intensity mechanical signals
      to spinal WDR neurons. However, Na(v)1.8 sodium channels on central terminals
      seem to be key to the modulation of spontaneous firing in SNL rats.

PMID- 18089841
TI  - Doxycycline attenuates isoproterenol- and transverse aortic banding-induced
      cardiac hypertrophy in mice.
AB  - The United States Food and Drug Administration-approved antibiotic doxycycline
      (DOX) inhibits matrix metalloproteases, which contribute to the development of
      cardiac hypertrophy (CH). We hypothesized that DOX might serve as a treatment for
      CH. The efficacy of DOX was tested in two mouse models of CH: induced by the beta
      adrenergic agonist isoproterenol (ISO) and induced by transverse aortic banding.
      DOX significantly attenuated CH in these models, causing a profound reduction of
      the hypertrophic phenotype and a lower heart/body weight ratio (p < 0.05, n >/=
      6). As expected, ISO increased matrix metalloprotease (MMP) 2 and 9 activities,
      and administration of DOX reversed this effect. Transcriptional profiles of
      normal, ISO-, and ISO + DOX-treated mice were examined using microarrays, and the
      results were confirmed by real-time reverse transcriptase-polymerase chain
      reaction. Genes (206) were differentially expressed between normal and ISO mice
      that were reversibly altered between ISO- and ISO + DOX-treated mice, indicating
      their potential role in CH development and DOX-induced improvement. These genes
      included those involved in the regulation of cell proliferation and fate, stress,
      and immune responses, cytoskeleton and extracellular matrix organization, and
      cardiac-specific signal transduction. The overall gene expression profile
      suggested that MMP2/9 inactivation was not the only mechanism whereby DOX exerts
      its beneficial effects. Western blot analysis identified potential signaling
      events associated with CH, including up-regulation of endothelial differentiation
      sphingolipid G-protein-coupled receptor 1 receptor and activation of
      extracellular signal-regulated kinase, p38, and the transcription factor
      activating transcription factor-2, which were reduced after administration of
      DOX. These results suggest that DOX might be evaluated as a potential CH
      therapeutic and also provide potential signaling mechanisms to investigate in the
      context of CH phenotype development and regression.

PMID- 18089842
TI  - Plitidepsin has a dual effect inhibiting cell cycle and inducing apoptosis via
      Rac1/c-Jun NH2-terminal kinase activation in human melanoma cells.
AB  - Melanoma is the most aggressive skin cancer and a serious health problem
      worldwide because of its increasing incidence and the lack of satisfactory
      chemotherapy for late stages of the disease. The marine depsipeptide Aplidin
      (plitidepsin) is an antitumoral agent under phase II clinical development against
      several neoplasias, including melanoma. We report that plitidepsin has a dual
      effect on the human SK-MEL-28 and UACC-257 melanoma cell lines; at low
      concentrations (</=45 nM), it inhibits the cell cycle by inducing G(1) and G(2)/M
      arrest, whereas at higher concentrations it induces apoptosis as assessed by poly
      (ADP-ribose) polymerase cleavage and the appearance of a hypodiploid peak in flow
      cytometry analyses. Plitidepsin activates Rac1 GTPase and c-Jun NH(2)-terminal
      kinase (JNK). In addition, it induces AKT and p38 mitogen-activated protein
      kinase (MAPK) phosphorylation. By using inhibitors, we found that JNK and p38
      MAPK activation depends on Rac1 but not on phosphatidylinositol 3-kinase (PI3K),
      whereas AKT activation is independent of Rac1 but requires PI3K activity.
      Plitidepsin cytotoxicity diminishes by Rac1 inhibition or by the blockage of JNK
      and p38 MAPK using 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H
      imidazole (SB203580), but not by PI3K inhibition using wortmannin or 2-(4
      morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). It is remarkable that
      plitidepsin and dacarbazine, the alkylating agent most active for treating
      metastatic melanoma, show a synergistic antiproliferative effect that was
      paralleled at the level of JNK activation. These results indicate that Rac1/JNK
      activation is critical for cell cycle arrest and apoptosis induction by
      plitidepsin in melanoma cells. They also support the combined use of plitidepsin
      and dacarbazine in in vivo studies.

PMID- 18089843
TI  - The triple uptake inhibitor (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3
      azabicyclo[3.1.0] hexane hydrochloride (DOV 21947) reduces body weight and plasma
      triglycerides in rodent models of diet-induced obesity.
AB  - Selective inhibitors of biogenic amine (e.g., serotonin, norepinephrine, and
      dopamine) uptake exhibit varying degrees of safety and efficacy as antiobesity
      agents. Moreover, preclinical findings suggest that the combined inhibition of
      monoamine neurotransmitter transporters synergistically enhances antiobesity
      activity. (1R,5S)-(+)-1-(3,4-Dichlorophenyl)-3-azabicyclo-[3.1.0] hexane
      hydrochloride (DOV 21947) inhibits norepinephrine, 5-hydroxytryptamine, and
      dopamine uptake, and it reduces body weight in rodent models of diet-induced
      obesity (DIO). DIO rats treated orally with DOV 21947 for 1 to 24 days showed
      significantly lower body weights than vehicle-treated DIO rats. The decrease in
      body weight resulted specifically from a loss of retroperitoneal and mesenteric
      depots of white adipose tissue. DOV 21947 also reduced daily food intake in DIO
      rats, but consumption returned to control levels after 11 days of treatment. With
      the exception of a decrease in triglyceride levels, blood chemistry was unaltered
      after 24 days of DOV 21947 treatments. DOV 21947 had no effect on motor activity.
      Although DOV 21947 increased respiratory rate and decreased the tidal volume of
      normal rats, it did not alter the minute volume. In addition, DOV 21947 did not
      significantly affect blood pressure, heart rate, electrocardiographic indices or
      body temperature in telemeterized dogs. However, it caused a sustained, but
      reversible reduction in the rate of body weight gain for as long as 6 months in
      normal rats, and for up to 1 year in normal dogs. In summary, DOV 21947 is
      effective in causing a sustained and selective reduction in fat content and
      triglyceride levels in animal models of obesity without significantly altering
      vital organ function.

PMID- 18089844
TI  - Estrogen receptor-independent neuroprotection via protein phosphatase
      preservation and attenuation of persistent extracellular signal-regulated kinase
      1/2 activation.
AB  - The mechanism of estrogen-mediated neuroprotection is not yet clear. Estrogens
      have a variety of modes of action, including transducing signaling events such as
      activation and/or suppression of the mitogen-activated protein kinase (MAPK)
      pathway. We have previously shown protein phosphatases to be involved in 17beta
      estradiol-mediated neuroprotection. In the present study, we assessed the role of
      estrogen receptors (ERs) in estrogen-mediated neuroprotection from
      oxidative/excitotoxic stress and the consequential effects on MAPK signaling.
      Okadaic acid and calyculin A, nonspecific serine/threonine phosphatase
      inhibitors, were exposed to cells at various concentrations in the presence or
      absence of 17alpha-estradiol, the enantiomer of 17beta-estradiol, 2-(1-adamantyl)
      3-hydroxyestra-1,3,5(10)-trien-17-one (ZYC3; non-ER-binding estrogen analog),
      and/or glutamate. All three compounds, which we have shown to have little or no
      binding to ERalpha and ERbeta, were protective against glutamate toxicity but not
      against okadaic acid and calyculin A toxicity. In addition, in the presence of
      effective concentrations of these inhibitors, the protective effects of these
      estrogen analogs were lost. Glutamate treatment caused a 50% decrease in levels
      of protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A), and protein
      phosphatase 2B (calcineurin) (PP2B). Coadministration of ZYC3 with glutamate
      prevented the decreases in PP1, PP2A, and PP2B levels. Furthermore, glutamate
      treatment caused a persistent increase in phosphorylation of extracellular signal
      regulated kinase (ERK) 1/2 that corresponds with the decrease protein levels of
      serine/threonine phosphatases. ZYC3 blocked this persistent increase in ERK
      phosphorylation. These results suggest that estrogens protect cells against
      glutamate-induced oxidative stress through an ER-independent mediated mechanism
      that serves to preserve phosphatase activity in the face of oxidative insults,
      resulting in attenuation of the persistent phosphorylation of ERK associated with
      neuronal death.

PMID- 18089846
TI  - The effects of cyclooxygenase-2 expression in prostate cancer cells: modulation
      of response to cytotoxic agents.
AB  - Cyclooxygenase (COX)-2 has emerged as an exciting target for therapeutic
      intervention in the management of cancer. Immunohistochemistry studies have
      indicated higher expression of COX-2 in cancerous versus benign prostatic tissue.
      We have explored the role of COX-2 in prostate cancer in terms of attenuation of
      apoptosis and sensitivity to pharmacological agents, including COX-2 inhibitors.
      The human prostate cancer cell line LNCaP was stably transfected with COX-2
      (LNCaPCOX-2) and compared with the empty vector control line (LNCaPneo).
      Chemosensitivity testing indicated no change in sensitivity to the cytotoxic
      effects of COX-2 inhibitors celecoxib or sulindac or VP16. However, LNCaPCOX-2
      cells showed 3-fold resistance to carboplatin, which was partially reversed by
      coincubation with the phosphatidylinositol 3-kinase inhibitor wortmannin.
      Concomitant with reduced apoptotic response to cytotoxic agents, LNCaPCOX-2 cells
      expressed increased levels of survivin and Bcl-2 with enhanced activation of AKT.
      We also investigated the effects of celecoxib on expression levels of genes
      relevant to prostate cancer and drug resistance in our model system using
      quantitative polymerase chain reaction analysis. Celecoxib treatment resulted in
      highly significant increases in the mRNA expression of the smooth muscle
      component desmin, the detoxification enzyme glutathione S-transferase pi (GSTpi),
      and nonsteroidal anti-inflammatory response gene (NAG-1) in the LNCaPCOX-2 cell
      line compared with LNCaPneo cells. Significant decreases in survivin levels and
      increases in GSTpi and NAG-1 appeared to be COX-2-dependent effects because they
      were more pronounced in LNCaPCOX-2 cells. Our findings indicate both COX-2
      dependent and -independent mechanisms attributable to celecoxib and support its
      utility in the management of prostate cancer.

PMID- 18089845
TI  - 2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with
      longer lasting action in vivo than salvinorin A.
AB  - Salvinorin (Sal) A is a naturally occurring, selective kappa opioid receptor
      (KOPR) agonist with a short duration of action in vivo. Pharmacological
      properties of a C(2) derivative, 2-methoxymethyl (MOM)-Sal B, were characterized.
      MOM-Sal B bound to KOPR with high selectivity and displayed approximately 3-fold
      higher affinity than U50,488H [(trans)-3,4-dichloro-N-methyl-N-[2-(1
      pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate] and Sal A. It acted
      as a full agonist at KOPR in guanosine 5'-O-(3-[(35)S]thio)triphosphate binding
      and was approximately 5- and approximately 7-fold more potent than U50,488H and
      Sal A, respectively. In Chinese hamster ovary cells stably expressing KOPR, all
      three kappa agonists internalized or down-regulated KOPR to similar extents, with
      MOM-Sal B being the most potent. In mice, MOM-Sal B (0.05-1 mg/kg s.c.) caused
      immediate and dose-dependent immobility lasting approximately 3 h, which was
      blocked by norbinaltorphimine. In contrast, ambulation in a Y-maze was increased
      when rats received MOM-Sal B (1-5 mg/kg s.c.). In addition, MOM-Sal B (0.5-5
      mg/kg i.p.) produced antinociception (hot-plate test) and hypothermia in a dose
      dependent manner in rats. MOM-Sal B was more potent than U50,488H in both tests
      and more efficacious than U50,488H in the hot-plate test. These latter two in
      vivo effects were blocked by norbinaltorphimine, indicating KOPR-mediated
      actions. Sal A at 10 mg/kg elicited neither antinociception nor hypothermia 30
      min after administration to rats. In summary, MOM-Sal B is a potent and
      efficacious KOPR agonist with longer lasting in vivo effects than Sal A.

PMID- 18089847
TI  - Identification, classification, and expression of RAGE gene splice variants.
AB  - The receptor for advanced glycation end-products (RAGE) is a single
      transmembrane, multiligand receptor of the immunoglobulin superfamily. RAGE up
      regulation is implicated in numerous pathological states including vascular
      disease, diabetes, cancer, and neurodegeneration. The understanding of the
      regulation of RAGE is important in both disease pathogenesis and normal
      homeostasis. Here, we demonstrate the characterization and identification of
      human RAGE splice variants by analysis of RAGE cDNA from tissue and cells. We
      identified a vast range of splice forms that lead to changes in the protein
      coding region of RAGE, which we have classified according to the Human Gene
      Nomenclature Committee (HGNC). These resulted in protein changes in the ligand
      binding domain of RAGE or the removal of the transmembrane domain and cytosolic
      tail. Analysis of splice variants for premature termination codons reveals
      approximately 50% of identified variants are targeted to the nonsense-mediated
      mRNA decay pathway. Expression analysis revealed the RAGE_v1 variant to be the
      primary secreted soluble isoform of RAGE. Taken together, identification of
      functional splice variants of RAGE underscores the biological diversity of the
      RAGE gene and will aid in the understanding of the gene in the normal and
      pathological state.

PMID- 18089848
TI  - Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and
      chemotaxis of hematopoietic progenitor cells.
AB  - RhoH, a hematopoietic-specific and constitutively active member of the Rho
      guanosine triphosphatase (GTPase) family, has been implicated in the negative
      regulation of Rac GTPase-mediated signaling in hematopoietic cells. However, the
      molecular mechanisms underlying the functional interaction between RhoH and Rac
      in primary cells are poorly understood. Here we show that deletion of Rhoh in
      hematopoietic progenitor cells (HPCs) leads to increased stromal-derived factor
      1alpha (SDF-1alpha)-induced chemotaxis and chemokinesis (random migration). The
      abnormally enhanced migration of Rhoh(-/-) HPCs is associated with increased Rac1
      activity and translocation of Rac1 protein to the cell membrane, where it
      colocalizes with cortical filamentous-actin (F-actin) and lipid rafts. Expression
      of the dominant-negative mutant Rac1N17 inhibits the cortical F-actin assembly
      and chemotaxis of wild-type and Rhoh(-/-) HPCs to the same extent. Conversely,
      overexpression of RhoH in HPCs blocks the membrane translocation of Rac1-enhanced
      green fluorescence protein (EGFP) and active Rac1V12-EGFP proteins and impairs
      cortical F-actin assembly and chemotaxis in response to SDF-1alpha stimulation.
      Furthermore, we demonstrate that the subcellular localization and inhibitory
      function of RhoH in HPCs are regulated by C-terminal motifs, including a CKIF
      prenylation site. Together, we have identified an antagonistic role of RhoH in
      regulation of cortical F-actin assembly and chemotaxis via suppressing Rac1
      membrane targeting and activation in primary HPCs.

PMID- 18089849
TI  - High-dose compared with intermediate-dose methotrexate in children with a first
      relapse of acute lymphoblastic leukemia.
AB  - High-dose methotrexate (MTX) has been extensively used for treatment of acute
      lymphoblastic leukemia (ALL). To determine the optimal dose of MTX in childhood
      relapsed ALL, the ALL Relapse Berlin-Frankfurt-Munster (ALL-REZ BFM) Study Group
      performed this prospective randomized study. A total of 269 children with a first
      early/late isolated (n = 156) or combined (n = 68) bone marrow or any isolated
      extramedullary relapse (n = 45) of precursor B-cell (PBC) ALL (excluding very
      early marrow relapse within 18 months after initial diagnosis) were registered at
      the ALL-REZ BFM90 trial and randomized to receive methotrexate infusions at
      either 1 g/m(2) over 36 hours (intermediate dose, ID) or 5 g/m(2) over 24 hours
      (high dose, HD) during 6 (or 4) intensive polychemotherapy courses. Intensive
      induction/consolidation therapy was followed by cranial irradiation, and by
      conventional-dose maintenance therapy. Fifty-five children received stem-cell
      transplants. At a median follow-up of 14.1 years, the 10-year event-free survival
      probability was .36 (+/- .04) for the ID group (n = 141), and .38 (+/- .04) for
      the HD group (n = 128, P = .919). The 2 groups did not differ in terms of
      prognostic factors and other therapeutic parameters. In conclusion, methotrexate
      infusions at 5 g/m(2) per 24 hours, compared with 1 g/m(2) per 36 hours, are not
      associated with increased disease control in relapsed childhood PBC acute
      lymphoblastic leukemia.

PMID- 18089850
TI  - Improved outcome in multisystem Langerhans cell histiocytosis is associated with
      therapy intensification.
AB  - Multisystem Langerhans cell histiocytosis (MS-LCH) is associated with high
      mortality when patients have risk organ involvement (RO(+)) or are younger than 2
      years. In an international randomized trial, LCH-II, we intensified their
      treatment: arm A consisted of 6 weeks of daily prednisone and weekly vinblastine
      followed by 18 weeks of daily 6-mercaptopurine with vinblastine/prednisone
      pulses; etoposide was added in arm B. Considering all 193 randomized risk
      patients, there were similar outcomes: rapid (6 weeks) response (arm A vs arm B:
      63%/71%), 5-year survival probability (74%/79%), disease reactivation frequency
      (46%/46%), and permanent consequences (43%/37%). However, (1) patients younger
      than 2 years without RO involvement (RO(-)) had 100% survival and uniformly high
      (> 80%) rapid response, (2) RO(+) patients not responding within 6 weeks had
      highest mortality, and (3) importantly, the more intensive arm B reduced
      mortality in RO(+) patients (relative hazard rate, accounting for differences in
      risk organ involvement, of 0.54; 95% CI = 0.29-1.00). Finally, comparison of
      RO(+) patients in LCH-I and LCH-II confirmed that increasing treatment intensity
      increased rapid responses (from 43% in arm A LCH-I to 68% in arm B LCH-II; P =
      .027) and reduced mortality (from 44% in arm A LCH-I to 27% in arm B LCH-II; P =
      .042). We conclude that intensified treatment significantly increases rapid
      response and reduces mortality in risk MS-LCH. This trial was registered at
      http://www.controlled-trials.com as no. ISRCTN57679341.

PMID- 18089851
TI  - Activated protein C-cleaved protease activated receptor-1 is retained on the
      endothelial cell surface even in the presence of thrombin.
AB  - Activated protein C (APC) signals in endothelial cells ex vivo through protease
      activated receptor-1 (PAR1). However, it is controversial whether PAR1 can
      mediate APC's protective effects in sepsis because the inflammatory response
      results in thrombin generation and thrombin proteolytically activates PAR1 much
      more efficiently than APC. Here we show that APC can induce powerful barrier
      protective responses in an endothelial cell monolayer in the presence of
      thrombin. Using cell surface immunoassays with conformation sensitive monoclonal
      anti-PAR1 antibodies we analyzed cleavage of endogenous PAR1 on the endothelial
      cell surface by APC in the absence and presence of thrombin. Incubation with APC
      caused efficient PAR1 cleavage and upon coincubation with thrombin APC supported
      additional PAR1 cleavage. Thrombin-cleaved PAR1 rapidly disappeared from the cell
      surface whereas, unexpectedly, the APC-cleaved PAR1 remained and could be
      detected on the cell surface, even when thrombin at concentrations of up to 1 nM
      was also present. Our findings demonstrate for the first time directly that APC
      can generate a distinct PAR1 population on endothelial cells in the presence of
      thrombin. The data suggest that different trafficking of activated PAR1 might
      explain how PAR1 signaling by APC can be relevant when thrombin is present.

PMID- 18089852
TI  - MicroRNA expression profiling in classic Hodgkin lymphoma.
AB  - MicroRNAs (miRNAs) are negative regulators of gene expression that play an
      important role in hematopoiesis and tumorigenesis. We analyzed miRNA expression
      in classic Hodgkin lymphoma (cHL) and the influence of Epstein-Barr virus (EBV)
      infection on the miRNA expression profiles. The expression of 157 miRNAs in lymph
      nodes from 49 cHL patients and 10 reactive lymph nodes (RLNs) was analyzed by
      real-time polymerase chain reaction (PCR). Hierarchic clustering revealed 3 well
      defined groups: nodular sclerosis cHL, mixed cellularity cHL, and RLNs. A
      distinctive signature of 25 miRNAs differentiated cHL from RLNs, and 36 miRNAs
      were differentially expressed in the nodular sclerosis and mixed cellularity
      subtypes. These results were validated in a set of 30 cHLs and 5 RLNs, and in 3
      cHL cell lines. miR-96, miR-128a, and miR-128b were selectively down-regulated in
      cHL with EBV. Our findings suggest that miRNAs play an important role in the
      biology of cHL and may be useful in developing therapies targeting miRNAs.

PMID- 18089854
TI  - Hypoxia transcriptionally induces macrophage-inflammatory protein-3alpha/CCL-20
      in primary human mononuclear phagocytes through nuclear factor (NF)-kappaB.
AB  - Hypoxia, a condition of low oxygen tension, occurring in many pathological
      processes, modifies the mononuclear phagocyte transcriptional profile. Here, we
      demonstrate hypoxic up-regulation of the CCL20 chemokine in primary human
      monocytes (Mn) and macrophages. mRNA induction was paralleled by protein
      secretion and dependent on gene transcription activation. Functional studies of
      the CCL20 promoter using a series of 5'-deleted and mutated reporter constructs
      demonstrated the requirement for the NF-kappaB-binding site located at position 
      92/-82 for gene transactivation by hypoxia, as 1) transcription was abrogated by
      a 3-bp mutation of the NF-kappaB motif; 2) three copies of the wild-type NF
      kappaB-binding site conferred hypoxia responsiveness to a minimal heterologous
      promoter; and 3) hypoxia increased specific NF-kappaB binding to this sequence.
      Furthermore, we provide evidence of the specific role of a single NF-kappaB
      family member, p50, in mediating CCL20 gene transcription in hypoxic Mn. p50
      homodimers were the only detectable NF-kappaB complexes binding the cognate
      kappaB site on the CCL20 promoter upon hypoxia exposure, and NF-kappaBp50
      knockdown by lentiviral-mediated short hairpin RNA interference resulted in
      complete binding inhibition. NF-kappaBp50 overexpression in transient
      cotransfection studies promoted CCL20 gene transactivation, which was abrogated
      by mutation of the -92/-82 kappaB site. Moreover, nuclear expression of the other
      NF-kappaB family members was inhibited in hypoxic Mn. In conclusion, this study
      characterizes a previously unrecognized role for hypoxia as a transcriptional
      inducer of CCL20 in human mononuclear phagocytes and highlights the importance of
      the NF-kappaB pathway in mediating this response, with potential implications for
      inflammatory disease and cancer pathogenesis.

PMID- 18089853
TI  - Constitutive activation of SHP2 protein tyrosine phosphatase inhibits ICSBP
      induced transcription of the gene encoding gp91PHOX during myeloid
      differentiation.
AB  - The IFN consensus sequence-binding protein (ICSBP; also referred to as IFN
      regulatory factor 8) is a transcription factor which is expressed in myeloid and
      B cells. In previous studies, we found that ICSBP activated transcription of the
      gene encoding gp91(PHOX) (the CYBB gene), a rate-limiting component of the
      phagocyte respiratory burst oxidase expressed exclusively after the promyelocyte
      stage of myelopoiesis. Previously, we found that CYBB transcription was dependent
      on phosphorylation of specific ICSBP tyrosine residues. Since ICSBP is tyrosine
      phosphorylated during myelopoiesis, this provided a mechanism of differentiation
      stage-specific CYBB transcription. In the current studies, we found that ICSBP
      was a substrate for Src homology-containing tyrosine phosphatase 2 (SHP2-PTP) in
      immature myeloid cells but not during myelopoiesis. Therefore, SHP2-PTP inhibited
      CYBB transcription and respiratory burst activity in myeloid progenitor cells by
      dephosphorylating ICSBP. In contrast, we found that ICSBP was a substrate for a
      leukemia-associated, constitutively active mutant form of SHP2, described
      previously, throughout differentiation. Consistent with this, constitutive SHP2
      activation blocked ICSBP-induced CYBB transcription and respiratory burst
      activity in differentiating myeloid cells. ICSBP-deficiency and constitutive SHP2
      activation have been described in human myelodysplastic syndromes. As these two
      abnormalities may coexist, our results identified a potential molecular mechanism
      for impaired phagocyte function in this malignant myeloid disease.

PMID- 18089855
TI  - Incorporating work organisation into occupational health research: an invitation
      for dialogue.

PMID- 18089856
TI  - Workplace intervention and musculoskeletal disorders: the need to develop
      research on implementation strategy.

PMID- 18089857
TI  - Studies of SARM1 uncover similarities between immune and neuronal responses to
      danger.
AB  - Toll-interleukin-1 receptor (TIR) domain-containing proteins are best known as
      critical players in vertebrate immune defense against pathogens. Four of the five
      members of this family are required for the activation of immune cells downstream
      of the engagement of Toll-like receptors (TLRs) by microbial molecules. Mice
      deficient in any one of these four molecules show greatly enhanced susceptibility
      to specific classes of pathogens. However, the physiological function of the
      fifth mammalian protein, sterile alpha and TIR motif-containing 1 [SARM1, also
      known as myeloid differentiation marker 88-5 (MyD88-5)], has remained elusive.
      Now, the study of the SARM1 reporter and SARM1-deficient mice has uncovered an
      unanticipated function of this molecule in the regulation of neuronal survival in
      response to metabolic stress. Together with pioneering observations on the
      functions of TIR-1, the worm ortholog of SARM1, and other reports on the role of
      TLRs in neuronal development and responses to injury in mammals, these exciting
      results suggest that further studies of SARM1-deficient animals may uncover
      unexpected similarities between the ways in which neurons and immune cells sense
      and respond to danger.

PMID- 18089858
TI  - Image correlation spectroscopy.
AB  - Membrane domains, such as caveolae and clathrin-coated pits, regulate cell
      signaling and protein internalization in the plasma membrane. Fluorescence
      imaging and microscopy provide an opportunity to determine the receptor protein
      dynamics of membrane microdomains. The family of image correlation spectroscopy
      (ICS) techniques provides powerful tools with which to measure the aggregation,
      clustering, and dynamics of proteins in the plasma membrane. ICS is used to
      calculate the cluster density and the degree of aggregation of plasma membrane
      proteins, whereas image cross-correlation spectroscopy (ICCS) measures the
      fraction of colocalization of two proteins. Dynamic image correlation
      spectroscopy (DICS) can be used to analyze protein dynamics on the cell surface
      during live-cell imaging.

PMID- 18089859
TI  - Identification of redox-active cell-surface proteins by mechanism-based kinetic
      trapping.
AB  - A number of thiol-dependent oxidoreductases are released from cells and act on
      the cell surface. Correspondingly, several cell-surface processes appear to
      depend on catalyzed thiol-disulfide exchange, including integrin activation and
      the fusion of viral particles with the host membrane. Tumor cells frequently
      increase the abundance of secreted and cell-surface forms of particular
      oxidoreductases, and evidence suggests that oxidoreductases released from tumor
      cells promote growth and contribute to the remodeling of the cellular
      microenvironment. Few cell-surface or membrane proteins that are targeted by
      extracellular redox enzymes have been identified. One major reason for this slow
      progress is the highly transient nature of thiol-disulfide exchange, making its
      detection by conventional techniques difficult or impossible. Here we describe
      the application of an activity-based proteomics approach, also known as
      "mechanism-based kinetic trapping," to identify individual cell-surface target
      proteins that engage in disulfide exchange with thiol-dependent oxidoreductases.
      Although we have applied this approach to thioredoxin-1, it should also be
      applicable to other members of the thioredoxin superfamily whose activity is
      based on the CXXC active-site motif.

PMID- 18089861
TI  - Letting go of the hope that psychotherapy prolongs cancer survival.

PMID- 18089862
TI  - Questions about gemcitabine dose rate: answered or unanswered?

PMID- 18089863
TI  - Spiral computed tomography and lung cancer: science, the media, and public
      opinion.

PMID- 18089864
TI  - Survival after a psychoeducational intervention for patients with cutaneous
      malignant melanoma: a replication study.
AB  - PURPOSE: The results of a randomized, intervention study done in 1993 of
      psychoeducation for patients with early-stage malignant melanoma showed a
      beneficial effect on recurrence and survival 6 years after the intervention. In
      the present study, we replicated the study with 258 Danish patients with
      malignant melanoma. We also compared recurrence and survival among the
      participants in the randomized study with 137 patients who refused to
      participate. PATIENTS AND METHODS: We randomly assigned 262 patients with primary
      malignant melanoma to a control or an intervention group. Patients in the
      intervention group were offered six weekly 2-hour sessions of psychoeducation.
      Participants and nonparticipants were followed up for vital status and recurrence
      4 to 6 years after surgical treatment. Prognostic factors (thickness of the tumor
      and lymph node status), sex, and age were adjusted for in a Cox regression model
      (proportional hazards regression) to derive an adjusted survival rate ratio and
      an adjusted relapse-free survival rate ratio, with 95% CIs. RESULTS: The hazard
      ratio was 1.30 (95% CI, 0.5 to 3.5) for survival and 0.73 (95% CI, 0.3 to 1.9)
      for recurrence. Being a nonparticipant increased the risk for death by more than
      two-fold (hazard ratio, 2.26; 95% CI, 1.0 to 5.2) over that of participants.
      CONCLUSION: Psychoeducation did not increase survival or the recurrence-free
      interval among patients with malignant melanoma; however, nonparticipants had a
      statistically significantly greater risk for death than participants.

PMID- 18089865
TI  - Randomized crossover study evaluating the effect of gemcitabine infusion dose
      rate: evidence of auto-induction of gemcitabine accumulation.
AB  - PURPOSE: Controversy exists over the optimal dose rate for administration of
      gemcitabine. There is a strong pharmacologic rationale for increased
      intracellular accumulation with prolonged infusions, but this failed to translate
      into a significant benefit in a large randomized study. The purpose of this study
      was to compare the intracellular pharmacokinetics of gemcitabine given for 30
      minutes or for 100 minutes in a crossover design. PATIENTS AND METHODS: We
      randomly assigned 33 patients to a standard dose of 1,000 mg/m2 over either 30
      minutes or 100 minutes. At the second week, they were transferred to the
      alternate schedule. Blood samples were collected at various times after the
      gemcitabine infusion. Gemcitabine and difluorodeoxyuridine were measured in
      plasma by high-performance liquid chromatography (HPLC), and gemcitabine
      triphosphate was measured by HPLC in leukocytes. RESULTS: Intracellular
      accumulation was greater during the 100-minute infusion, which was consistent
      with previous data. This effect was confounded by an increase in gemcitabine
      triphosphate accumulation between weeks 1 and 2, which was consistent with self
      induction of gemcitabine accumulation. There was significant heterogeneity: 27%
      of patients had greater WBC accumulation during the 30-minute infusion
      (regardless of treatment order). Patients with relatively greater levels of
      gemcitabine-triphosphate in WBCs tended to have less under-dosing and a greater
      reduction in midcycle neutrophils. However, this observation did not correlate
      with plasma gemcitabine levels. CONCLUSION: This work identifies significant
      variations in intracellular gemcitabine-triphosphate accumulation between and
      within individuals, and it provides evidence that this variation has potential
      clinical significance. The observed self-induction of gemcitabine metabolism has
      broad implications for the dosing of nucleoside analogs.

PMID- 18089866
TI  - Health-related quality of life in patients treated for anaplastic
      oligodendroglioma with adjuvant chemotherapy: results of a European Organisation
      for Research and Treatment of Cancer randomized clinical trial.
AB  - PURPOSE: Little is known about the health-related quality of life (HRQOL) of
      patients treated for anaplastic oligodendrogliomas. The impact of combined
      procarbazine, CCNU (lomustine), and vincristine (PCV) chemotherapy after
      radiotherapy (RT) compared with RT alone on HRQOL in the randomized European
      Organisation for Research and Treatment of Cancer (EORTC) 26951 trial was
      studied. PATIENTS AND METHODS: Adult patients with anaplastic oligodendrogliomas
      received RT alone or RT plus PCV chemotherapy. HRQOL was assessed with the EORTC
      Quality of Life Questionnaire C30 and Brain Cancer Module. Seven prespecified
      HRQOL end points were selected. We hypothesized that chemotherapy would impair
      HRQOL during treatment but that there would be a similar HRQOL between treatment
      arms once off treatment. Assessments were performed at randomization, at the end
      of RT, and then every 3 to 6 months until progression. RESULTS: A total of 368
      patients were randomly assigned to one of the two arms; overall, 58% were male,
      and the median age was 49 years. Compliance with HRQOL was 78% at baseline and
      dropped to 55% to 72% up to 2.5 years post-RT. Baseline scores demonstrated
      considerable impairments in HRQOL for both treatment groups. The longitudinal
      analysis showed a significant increase in nausea/vomiting in the RT plus PCV
      chemotherapy arm during and shortly after chemotherapy. Because of a difference
      in baseline scores for fatigue and physical functioning, the differences between
      treatment arms during PCV did not reach significance. The nonselected scales of
      appetite loss and drowsiness demonstrated significant differences between
      treatment arms during chemotherapy in favor of the RT arm. The long-term results
      showed no difference between arms. CONCLUSION: The major impact of PCV on HRQOL
      is on nausea/vomiting, loss of appetite, and drowsiness during and shortly after
      treatment. There are no long-term effects of PCV chemotherapy.

PMID- 18089867
TI  - Prognostic value of health-related quality-of-life data in predicting survival in
      patients with anaplastic oligodendrogliomas, from a phase III EORTC brain cancer
      group study.
AB  - PURPOSE: This is one of a few studies that have explored the value of baseline
      symptoms and health-related quality of life (HRQOL) in predicting survival in
      patients with brain cancer. PATIENTS AND METHODS: Baseline HRQOL scores (from the
      European Organisation for Research and Treatment of Cancer [EORTC] Quality of
      Life Questionnaire C30 and the EORTC Brain Cancer Module) were examined in 247
      patients with anaplastic oligodendrogliomas to determine the relationship with
      overall survival by using Cox proportional hazards regression models. Refined
      techniques as the bootstrap resampling procedure and the computation of C indexes
      and R2 coefficients were used to explore the stability of the models as well as
      better assess the potential benefit of using HRQOL to predict survival in
      clinical practice and research. RESULTS: Classical analysis controlled for major
      clinical prognostic factors selected emotional functioning (P = .0016),
      communication deficit (P = .0261), future uncertainty (P = .0481), and weakness
      of legs (P = .0001) as statistically significant prognostic factors of survival.
      However, several issues question the validity of these findings and no single
      model was found to be preferable over all others. C indexes, which estimate the
      probability of a model to correctly predict which patient among a randomly chosen
      pair of patients will survive longer, and R2 coefficients, which measure the
      proportion of variability explained by the model, did not exhibit major
      improvement when adding selected or all HRQOL scores to clinical factors.
      CONCLUSION: While classical techniques lead to positive results, more refined
      analyses suggest that baseline HRQOL scores add relatively little to clinical
      factors to predict survival. These results may have implications for future use
      of HRQOL as a prognostic factor for patients with cancer.

PMID- 18089868
TI  - Poor survival for US Pacific Islander cancer patients: evidence from the
      Surveillance, Epidemiology, and End Results database: 1991 to 2004.
AB  - PURPOSE: Although racial and ethnic differences in cancer survival in the United
      States have been studied extensively, little is known about cancer survival in US
      Pacific Islanders (PIs), a fast-growing and economically disadvantaged minority
      group. METHODS: Using data from the US National Cancer Institute's Surveillance,
      Epidemiology, and End Results (SEER) registries, we compared cause-specific and
      all-cause survival for female breast, prostate, lung, colorectal, stomach and
      liver cancer for Native Hawaiians, Samoans, other PIs (including Tongans,
      Guamanians, and others), African Americans, and Native Americans with non
      Hispanic whites using Cox proportional hazards models. Separate models were
      fitted adjusting for demographic factors only and demographic and disease
      severity variables. RESULTS: Among all groups, Samoans were the most likely to
      present with advanced disease and had the worst cause-specific survival for all
      sites considered. Samoans had particularly poor results (adjusted for demographic
      variables only) for female breast (relative risk [RR] = 3.05; 95% CI, 2.31 to
      4.02), colorectal (RR = 1.82; 95% CI, 1.37 to 2.41) and prostate (RR = 4.82; 95%
      CI, 3.38 to 6.88) cancers. Native Hawaiians and other PIs also had significantly
      worse cause-specific survival than did non-Hispanic whites for most sites, but
      generally had better survival than African Americans or Native Americans.
      CONCLUSION: Much of the survival disadvantage for PI groups appears to be a
      result of late diagnosis, and thus targeted interventions have much potential to
      reduce cancer mortality in this group. More research is needed to find
      explanations for the particularly poor cancer survival for Samoans in the United
      States.

PMID- 18089869
TI  - Phase I/II study of sequential dose-intensified ifosfamide, cisplatin, and
      etoposide plus paclitaxel as induction chemotherapy for poor prognosis germ cell
      tumors by the German Testicular Cancer Study Group.
AB  - PURPOSE: To evaluate the feasibility and the toxicity of sequential, dose
      intensified chemotherapy combined with paclitaxel plus peripheral blood-derived
      hematopoietic stem-cell support (PBSC) for patients with untreated metastatic
      germ cell tumors (GCTs) who have poor International Germ Cell Consensus Cancer
      Group prognostic features. PATIENTS AND METHODS: Paclitaxel was added to high
      dose (HD) etoposide, ifosfamide, and cisplatin (VIP; etoposide 1,500 mg/m2,
      ifosfamide 10,000 mg/m2, and cisplatin 100 mg/m2; cumulative dose; days -6
      through -2 per cycle) at three dose levels (135, 175, and 225 mg/m2) applied on
      day -6. Cycles were supported by PBSC and granulocyte colony-stimulating factor.
      One cycle of standard VIP was administered before start of HD-VIP plus paclitaxel
      cycles to collect autologous PBSC. RESULTS: Fifty-two of 53 patients receiving
      152 cycles were assessable. As expected, myelosuppression was the major adverse
      effect. Median durations of leukocytes less than 1,000/microL and thrombocytes
      less than 25,000/microL were 6 and 4 days, respectively, independently of the
      dose of paclitaxel applied. WHO grade 2 neurotoxicity and grade 3 encephalopathy
      were observed in 5% of patients each. Other main adverse effects observed were
      stomatitis, diarrhea, and obstipation. Seventy-nine percent of patients achieved
      a favorable response to chemotherapy plus secondary surgery. After a median
      follow-up time of 41 months in surviving patients, the calculated 2- and 5-year
      survival rates were 77.6% (95% CI, 65.4% to 89.9%) and 75.2% (95% CI, 62.5% to
      87.8%), respectively. CONCLUSION: Dose-intensive, sequential HD-VIP plus
      paclitaxel up to a dose of 225 mg/m2 in patients with poor prognosis GCT is a
      feasible approach. The regimen warrants investigation for its therapeutic
      potential in an expanded cohort of poor prognosis GCT patients.

PMID- 18089871
TI  - Is failure to meet spiritual needs associated with cancer patients' perceptions
      of quality of care and their satisfaction with care?
AB  - PURPOSE: Few studies regarding patients' views about spirituality and health care
      have included patients with cancer who reside in the urban, northeastern United
      States. Even fewer have investigated the relationship between patients' spiritual
      needs and perceptions of quality and satisfaction with care. PATIENTS AND
      METHODS: Outpatients (N = 369) completed a questionnaire at the Saint Vincent's
      Comprehensive Cancer Center in New York, NY. The instrument included the Quality
      of End-of-Life Care and Satisfaction with Treatment quality-of-care scale and
      questions about spiritual and religious beliefs and needs. RESULTS: The
      participants' mean age was 58 years; 65% were female; 67% were white; 65% were
      college educated; and 32% had breast cancer. Forty-seven percent were Catholic;
      19% were Jewish; 16% were Protestant; and 6% were atheist or agnostic. Sixty-six
      percent reported that they were spiritual but not religious. Only 29% attended
      religious services at least once per week. Seventy-three percent reported at
      least one spiritual need; 58% thought it appropriate for physicians to inquire
      about their spiritual needs. Eighteen percent reported that their spiritual needs
      were not being met. Only 6% reported that any staff members had inquired about
      their spiritual needs (0.9% of inquiries by physicians). Patients who reported
      that their spiritual needs were not being met gave lower ratings of the quality
      of care (P = .009) and reported lower satisfaction with care (P = .006).
      CONCLUSION: Most patients had spiritual needs. A slight majority thought it
      appropriate to be asked about these needs, although fewer thought this compared
      with reports in other settings. Few had their spiritual needs addressed by the
      staff. Patients whose spiritual needs were not met reported lower ratings of
      quality and satisfaction with care.

PMID- 18089870
TI  - Oncologist communication about emotion during visits with patients with advanced
      cancer.
AB  - INTRODUCTION: Cancer care involves addressing patient emotion. When patients
      express negative emotions, empathic opportunities emerge. When oncologists
      respond with a continuer statement, which is one that offers empathy and allows
      patients to continue expressing emotions, rather than with a terminator
      statement, which is one that discourages disclosure, patients have less anxiety
      and depression and report greater satisfaction and adherence to therapy. We
      studied whether oncologist traits were associated with empathic opportunities and
      empathic responses. PATIENTS AND METHODS: We audio-recorded 398 clinic
      conversations between 51 oncologists and 270 patients with advanced cancer;
      oncologists also completed surveys. Conversations were coded for the presence of
      empathic opportunities and oncologist responses. Analyses examined the
      relationship with oncologists' demographics, self-reported confidence, outcome
      expectancies, and comfort to address social versus technical aspects of care.
      RESULTS: In 398 conversations, 37% contained at least one empathic opportunity;
      the range was 0 to 10, and the total empathic opportunities was 292. When they
      occurred, oncologists responded with continuers 22% of the time. Oncologist sex
      was related to the number of empathic opportunities; female patients seen by
      female oncologists had the most empathic opportunities (P = .03). Younger
      oncologists (P = .02) and those who rated their orientation as more
      socioemotional than technical (P = .03) were more likely to respond with empathic
      statements. CONCLUSION: Oncologists encountered few empathic opportunities and
      responded with empathic statements infrequently. Empathic responses were more
      prevalent among younger oncologists and among those who were self-rated as
      socioemotional. To reduce patient anxiety and increase patient satisfaction and
      adherence, oncologists may need training to encourage patients to express
      emotions and to respond empathically to patients' emotions.

PMID- 18089872
TI  - Involvement of family physicians in the care of cancer patients seen in the
      palliative Rapid Response Radiotherapy Program.
AB  - PURPOSE: It is important for cancer patients to maintain continuity of care with
      their family physician (FP) while being followed at the cancer center. The
      primary objective of this study was to determine the perception of patients seen
      in the palliative Rapid Response Radiotherapy Program (RRRP) on FP involvement in
      their cancer care. Secondary objectives were to identify factors predicting for
      perceived FP involvement in patient cancer care. PATIENTS AND METHODS:
      Consecutive patients were approached for study enrollment at the time of RRRP
      visit and asked to complete a 15-item survey. RESULTS: Three hundred sixty-five
      patients were accrued over 15 months. Ninety-eight percent had an FP, and 43%
      felt their FP was involved in their cancer care. Eighty percent of patients were
      satisfied with the overall medical care provided by their FP, and 71% had been
      with their FP for > or = 5 years. The most common reason patients gave for
      perceiving limited FP involvement was the medical oncologist looking after all of
      their cancer needs. Multivariate analysis found that satisfaction with overall
      medical care provided by the FP, shorter time since last FP visit, seeing the FP
      since cancer diagnosis, and FP providing on-call service for after-hour
      emergencies all significantly predicted for patients perceiving FP involvement in
      their cancer care. CONCLUSION: Less than half of patients surveyed perceived
      their FP as involved in their cancer care. Encouraging continuity of care between
      patients and FPs may allow for easier transition of care back to the FP once
      palliative treatment at the cancer center has finished and help facilitate end-of
      life planning.

PMID- 18089873
TI  - Microbial spectrum and antibiotic susceptibility profile of gram-positive aerobic
      bacteria isolated from cancer patients.
AB  - PURPOSE: Cancer patients are particularly susceptible to nosocomial infections
      because of their compromised immune system, and because of the nature of
      treatment practices they experience. Recently, a shift of the microbial spectrum
      of cancer patients from gram-negative to gram-positive has been demonstrated.
      This study analyzed the distribution and the antimicrobial resistance of gram
      positive bacteria isolated from cancer patients in Egypt. PATIENTS AND METHODS:
      We examined the microbial spectrum of gram-positive bacteria in patients with
      hematologic malignancies and solid tumors. In addition, we also studied the
      antimicrobial resistance of pathogens accounting for the majority of gram
      positive infections in these cancer patients. RESULTS: Most of gram-positive
      isolates from urinary tract (100%), respiratory tract (89.7%), and bloodstream
      infections (BSIs; 65.5%) were obtained from leukemic patients. All gram-positive
      isolates from skin infections were isolated from solid-tumor patients. In both
      leukemic and solid-tumor patients, gram-positive bacteria causing nosocomial BSI
      were mainly Coagulase-negative staphylococcus (CNS) and S. aureus, whereas gram
      positive bacteria causing nosocomial RTI were mainly alpha-hemolytic streptococci
      and CNS. Gram-positive bacteria were not isolated from GI tract infections. S.
      aureus, CNS, and alpha-hemolytic streptococci demonstrated methicillin resistance
      (81.5%, 92.3%, and 90% resistance, respectively). S. aureus and CNS were
      susceptible to linezolid (15.4% and 0% resistance, respectively), and vancomycin
      (15.5% and 11% resistance, respectively). CONCLUSION: This is the first study to
      report the emergence of vancomycin- and linezolid-resistant S. aureus in Egypt.
      Newer generation quinolones (moxifloxacin and gatifloxacin) were more active than
      older quinolones (ciprofloxacin and ofloxacin) against S. aureus and CNS,
      suggesting the use of newer generation quinolones in the prophylaxis of cancer
      patients.

PMID- 18089874
TI  - Symptoms and patient-reported well-being: do they predict survival in malignant
      pleural mesothelioma? A prognostic factor analysis of EORTC-NCIC 08983:
      randomized phase III study of cisplatin with or without raltitrexed in patients
      with malignant pleural mesothelioma.
AB  - PURPOSE: Malignant pleural mesothelioma (MPM) is a rare disease. Unlike other
      advanced cancer types, little is known about patient-reported symptoms or health
      related quality of life (HRQOL) and their possible prognostic value. This study
      reports an evaluation of the prognostic value of these factors using data
      gathered from a recent randomized controlled trial. PATIENTS AND METHODS:
      Patients were entered onto this trial if they had a histologically proven
      unresectable MPM, not pretreated with chemotherapy, WHO performance status < or =
      2, and adequate hematologic, renal, and hepatic function. Patients were randomly
      assigned to receive cisplatin 80 mg/m2 intravenously on day 1, without or with
      preceding infusion of raltitrexed 3 mg/m2. HRQOL was assessed using the European
      Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30/Lung Cancer 13
      tool. The Cox proportional hazards regression model was used for the univariate
      and multivariate analyses of survival, along with a bootstrap validation
      technique. Included were the EORTC prognostic index (PI) composed of stage of
      disease, histology type, time since diagnosis, and WBC, and, in addition, 10
      selected key symptoms and HRQOL scales. RESULTS: Two hundred fifty patients were
      randomly assigned (80% male; median age, 58 years; WHO performance status 0, 1, 2
      in 25%, 62%, and 13% of cases, respectively). Two hundred twenty-nine patients
      (91.6%) had a valid HRQOL assessment. The final multivariate model retained the
      PI, pain (P < .0001), and appetite loss (P = .0100) as independent prognostic
      indicators of survival. CONCLUSION: Results suggest that the PI, pain, and
      appetite loss may be independent prognostic factors in patients with advanced
      MPM.

PMID- 18089875
TI  - Randomized phase II study of gemcitabine plus cisplatin or carboplatin
      [corrected], with or without cetuximab, as first-line therapy for patients with
      advanced or metastatic non small-cell lung cancer.
AB  - PURPOSE: To evaluate the efficacy of cetuximab added to first-line
      gemcitabine/platinum in chemotherapy-naive patients with advanced non-small-cell
      lung cancer (NSCLC). PATIENTS AND METHODS: In this noncomparative, randomized
      trial, chemotherapy-naive patients with recurrent/metastatic NSCLC (stage IV or
      stage IIIB with malignant pleural effusion) were eligible. Patients received
      cisplatin (75 mg/m2 i.v., every 3 weeks) or carboplatin (area under the
      concentration-versus-time curve of 5 intravenously [i.v.], every 3 weeks), and
      gemcitabine (1,250 or 1,000 mg/m2 i.v., days 1 and 8) plus cetuximab (400 mg/m2
      i.v. day 1, followed by 250 mg/m2 weekly), in arm A, or chemotherapy alone, in
      arm B. Response rate was the primary end point; safety, progression-free
      survival, and overall survival were secondary end points. RESULTS: Sixty-five
      patients were randomly assigned to arm A and 66 to arm B. Partial responses were
      observed in 18 patients (27.7%; 95% CI, 17.3 to 40.2) in arm A and 12 (18.2%; 95%
      CI, 9.8 to 29.6) in arm B. Median progression-free survival was 5.09 months for
      arm A (95% CI, 4.17 to 5.98) and 4.21 months (95% CI, 3.81 to 5.49) in arm B.
      Median overall survival was 11.99 months (95% CI, 8.80 to 15.18) and 9.26 months
      (95% CI, 7.43 to 11.79) in arms A and B, respectively. Overall toxicity was
      acceptable and consistent with the profiles of the individual agents. CONCLUSION:
      First-line treatment with cetuximab plus gemcitabine/platinum is well tolerated
      and can be administered safely in patients with advanced NSCLC. Differences in
      response rate, progression-free survival, and overall survival suggest that the
      addition of cetuximab to platinum/gemcitabine may improve clinical outcomes.
      Larger studies are in progress to address this hypothesis.

PMID- 18089877
TI  - Beyond the traditional prognostic indicators: the impact of primary care
      utilization on cancer survival.
AB  - PURPOSE: To our knowledge to date, the effect of primary care utilization on
      health outcomes in cancer patients has not been described. The objective of this
      study was to investigate the impact of primary care utilization within 6 months
      of cancer diagnosis on survival in patients with lung cancer. PATIENTS AND
      METHODS: We used electronic medical record data (1997 to 2005) to identify male
      veterans with incident lung cancers (N = 323). Primary care utilization was
      assessed in the 6 months after cancer diagnosis. Patients were observed from
      cancer diagnosis to death or to last date of health care utilization (ie,
      censoring date). Univariate and multivariate Cox proportional hazards models
      tested whether primary care utilization was associated with improved survival.
      Multivariate analyses adjusted for demographic and clinical characteristics.
      RESULTS: During an average follow-up of 16.6 months, 259 patients died. In
      multivariate analysis, the risk of death was 36% (hazard ratio [HR], 0.64; 95%
      CI, 0.45 to 0.90), 56% (HR, 0.44; 95% CI, 0.29 to 0.65), and 57% (HR, 0.43; 05%
      CI, 0.29 to 0.64) lower for patients who had one, two, or at least three primary
      care visits, respectively, in the first 6 months after cancer diagnosis as
      compared with those without primary care utilization. The median survival
      duration (P < .0001, log-rank test) was 3.68, 7.52, 13.88, and 13.75 months for
      patients with no, one, two, or at least three primary care visits, respectively.
      CONCLUSION: Primary care utilization in the early phase of cancer treatment has a
      marked effect that results in a reduced mortality risk in patients with incident
      lung cancer. Additional research is required to determine how and why primary
      care utilization is an important prognostic indicator of prolonged survival in
      patients with lung cancer.

PMID- 18089876
TI  - Reproductive factors, hormone use, estrogen receptor expression and risk of non
      small-cell lung cancer in women.
AB  - PURPOSE: Estrogen receptor (ER) expression in lung tumors suggests that estrogens
      may play a role in the development of lung cancer. We evaluated the role of
      hormone-related factors in determining risk of non-small-cell lung cancer (NSCLC)
      in women. We also evaluated whether risk factors were differentially associated
      with cytoplasmic ER-alpha and/or nuclear ER-beta expression-defined NSCLC in
      postmenopausal women. PATIENTS AND METHODS: Population-based participants
      included women aged 18 to 74 years diagnosed with NSCLC in metropolitan Detroit
      between November 1, 2001 and October 31, 2005. Population-based controls were
      identified through random digit dialing, matched to patient cases on race and 5
      year age group. Interview data were analyzed for 488 patient cases (241 with
      tumor ER results) and 498 controls. RESULTS: Increased duration of hormone
      replacement therapy (HRT) use in quartiles was associated with decreased risk of
      NSCLC in postmenopausal women (odds ratio = 0.88; 95% CI, 0.78 to 1.00; P = .04),
      adjusting for age, race, pack-years, education, family history of lung cancer,
      current body mass index, years exposed to second-hand smoke in the workplace, and
      obstructive lung disease history. Among postmenopausal women, ever using HRT,
      increasing HRT duration of use in quartiles, and increasing quartiles of estrogen
      use were significant predictors of reduced risk of NSCLC characterized as ER
      alpha and/or ER-beta positive. None of the hormone-related variables were
      associated with nuclear ER-alpha- or ER-beta-negative NSCLC. CONCLUSION: These
      findings suggest that postmenopausal hormone exposures are associated with
      reduced risk of ER-alpha- and ER-beta-expressing NSCLC. Understanding tumor
      characteristics may direct development of targeted treatment for this disease.

PMID- 18089878
TI  - Outcome after relapse among children with standard-risk acute lymphoblastic
      leukemia: Children's Oncology Group study CCG-1952.
AB  - PURPOSE: The event-free survival (EFS) of children with standard-risk acute
      lymphoblastic leukemia (SR-ALL) is now more than 80%. However, prognosis after
      relapse continues to be poor. We examined postrelapse outcomes of children
      initially treated on the Children's Cancer Group CCG-1952 study. PATIENTS AND
      METHODS: We evaluated outcomes after bone marrow (BM) relapse and isolated
      extramedullary (EM) relapse for 347 patients with SR-ALL (WBC < 50,000/microL;
      age, 1 to 9 years). The prognostic significance of several factors for EFS after
      relapse (EFS2) was assessed by Cox regression analysis. Stem-cell transplant
      (SCT) was compared with chemotherapy as salvage treatment. RESULTS: The mean +/-
      SE times to isolated central nervous system relapse, BM relapse, and isolated
      testicular relapse were 23 +/- 1 months (range, 1 to 88 months), 36 +/- 1 months
      (range, 2 to 79 months), and 40 +/- 2 months (range, 16 to 64 months),
      respectively. The estimated percent +/- SE 3-year EFS2 and overall survival rates
      after BM relapse were 37% +/- 4% and 46% +/- 4%, respectively, and rates after
      isolated EM relapse were 57% +/- 5% and 71% +/- 5%, respectively. By multivariate
      analysis, we found the duration of first remission to be the most significant
      predictor of EFS2 for either BM relapse or isolated EM relapse. Outcome was
      equivalent with SCT or chemotherapy after early or late relapse of SR-ALL at any
      site. CONCLUSION: Duration of first remission remains the most significant
      predictor of outcome after either BM or isolated EM relapse of SR-ALL. Prognosis
      after early BM relapse remains poor and is not improved with SCT in this cohort.

PMID- 18089879
TI  - Colorectal carcinoma in childhood and adolescence: a clinicopathologic review.
AB  - PURPOSE: Pediatric colorectal carcinoma (CRC) is rare, but the available data
      suggest that it is more likely than adult CRC to be advanced at presentation and
      to have a poor outcome. We sought to better characterize pediatric CRC. PATIENTS
      AND METHODS: We reviewed the clinical and pathologic features, prognostic
      factors, and outcome of CRC in 77 children and adolescents (ages 7 to 19 years)
      referred to St Jude Children's Research Hospital between 1964 and 2003. RESULTS:
      At presentation, 76 patients had one or more signs or symptoms of CRC (abdominal
      pain, altered bowel habits, weight loss, anemia). Tumors were evenly distributed
      between the right and left colon; 62% were mucinous adenocarcinoma. At
      presentation, 86% of patients had advanced-stage disease; more than half had
      distant metastases. Overall outcome was poor. Advanced stage and mucinous
      histology were significant predictors of adverse outcome. Stage-specific survival
      at 10 years was 67% +/- 27% (stage 1), 38% +/- 15% (stage 2), 28% +/- 11% (stage
      III), and 7% +/- 4% (stage 4). Although no patient had a diagnosis of polyposis
      syndrome before diagnosis of CRC, 17 (22%) had colon polyps and eight (including
      two who previously underwent pelvic radiotherapy) had multiple polyps.
      CONCLUSION: Initial signs and symptoms of CRC are similar in pediatric and adult
      patients. The strikingly higher frequency of mucinous histology suggests that the
      biology of CRC differs in pediatric and adult patients and may contribute to poor
      outcomes. Children should be included in prospective clinical trials for CRC.

PMID- 18089880
TI  - Primary cutaneous large B-cell lymphoma of the leg and acute hypercalcemia.

PMID- 18089881
TI  - Rectal GI stromal tumor mimicking a prostate mass.

PMID- 18089882
TI  - Carcinoma erysipeloides from ovarian clear-cell carcinoma.

PMID- 18089883
TI  - Does bigger mean better? British perspectives on American cancer treatment and
      research, 1948.
AB  - In the summer of 1948, a delegation representing the British Empire Cancer
      Campaign (BECC) toured North American cancer treatment and research facilities,
      and reported their observations back to their organization's executive board.
      This historical article contextualizes the British delegation's observations of
      US treatment and research, and discusses what the delegation made of the United
      States' new, "bigger" approaches to cancer surgery and chemotherapeutic research.
      I argue that the BECC delegation used their observations of US practice to
      reinforce a positive sense of British distinctiveness, thus reassuring themselves
      and their colleagues that Britain could still be a leader in the increasingly
      international field we now call oncology.

PMID- 18089884
TI  - Informed consent: true information or institutional review board-approved
      disinformation?

PMID- 18089885
TI  - Erlotinib in pancreatic cancer: are tumor cells the (only) target?

PMID- 18089886
TI  - MRI or bone scan or both for staging of prostate cancer?

PMID- 18089887
TI  - The debate about maintenance is not over in small-cell lung cancer.

PMID- 18089888
TI  - Enhanced local control by radiation boost in breast cancer: back side of the
      coin?

PMID- 18089889
TI  - What is the impact of tamoxifen on radiation-induced fibrosis in patients
      receiving breast-conserving therapy.

PMID- 18089890
TI  - Boost dose back again in elderly.

PMID- 18089891
TI  - Effects of a 1,3-diacylglycerol oil-enriched diet on postprandial lipemia in
      people with insulin resistance.
AB  - Postprandial hypertriglyceridemia is common in individuals with insulin
      resistance, and diets enriched in 1,3-diacylglycerol (DAG) may reduce
      postprandial plasma triglycerides (PPTGs). We enrolled 25 insulin-resistant,
      nondiabetic individuals in a double-blind, randomized crossover trial to test the
      acute and chronic effects of a DAG-enriched diet on PPTG. Participants received
      either DAG or triacylglycerol (TAG) oil, in food products, for 5 weeks. Fasting
      lipids, and two separate postprandial tests, one with DAG oil and one with TAG
      oil, were performed at the end of each 5 week diet period. We found no acute or
      chronic effects of DAG oil on PPTG. Thus, neither the DAG oil PPTG (h/mg/dl) on a
      chronic TAG diet [area under the curve (AUC) = 503 +/- 439] nor the TAG oil PPTG
      on a chronic DAG diet (AUC = 517 +/- 638) was different from the TAG oil PPTG on
      a chronic TAG diet (AUC = 565 +/- 362). Five weeks of a DAG-enriched diet had no
      acute or chronic effects on PPTG in insulin-resistant individuals. We suggest
      further studies to evaluate the effects of DAG on individuals with low and high
      TG levels.

PMID- 18089892
TI  - Multifactorial assessment and targeted intervention for preventing falls and
      injuries among older people in community and emergency care settings: systematic
      review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effectiveness of multifactorial assessment and
      intervention programmes to prevent falls and injuries among older adults
      recruited to trials in primary care, community, or emergency care settings.
      DESIGN: Systematic review of randomised and quasi-randomised controlled trials,
      and meta-analysis. DATA SOURCES: Six electronic databases (Medline, Embase,
      CENTRAL, CINAHL, PsycINFO, Social Science Citation Index) to 22 March 2007,
      reference lists of included studies, and previous reviews. REVIEW METHODS:
      Eligible studies were randomised or quasi-randomised trials that evaluated
      interventions to prevent falls that were based in emergency departments, primary
      care, or the community that assessed multiple risk factors for falling and
      provided or arranged for treatments to address these risk factors. DATA
      EXTRACTION: Outcomes were number of fallers, fall related injuries, fall rate,
      death, admission to hospital, contacts with health services, move to
      institutional care, physical activity, and quality of life. Methodological
      quality assessment included allocation concealment, blinding, losses and
      exclusions, intention to treat analysis, and reliability of outcome measurement.
      RESULTS: 19 studies, of variable methodological quality, were included. The
      combined risk ratio for the number of fallers during follow-up among 18 trials
      was 0.91 (95% confidence interval 0.82 to 1.02) and for fall related injuries
      (eight trials) was 0.90 (0.68 to 1.20). No differences were found in admissions
      to hospital, emergency department attendance, death, or move to institutional
      care. Subgroup analyses found no evidence of different effects between
      interventions in different locations, populations selected for high risk of falls
      or unselected, and multidisciplinary teams including a doctor, but interventions
      that actively provide treatments may be more effective than those that provide
      only knowledge and referral. CONCLUSIONS: Evidence that multifactorial fall
      prevention programmes in primary care, community, or emergency care settings are
      effective in reducing the number of fallers or fall related injuries is limited.
      Data were insufficient to assess fall and injury rates.

PMID- 18089893
TI  - The influence of achievement motivation and chess-specific motivation on
      deliberate practice.
AB  - Although the importance of high motivation to engage in deliberate practice has
      been acknowledged, no research has directly tested this hypothesis. Therefore,
      the present study examined this relation in adolescent elite chess players by
      means of a questionnaire. In addition, to provide an explanation for dropout
      among promising chess players, differences in motivation between persistent and
      dropout chess players were analyzed. Competitiveness and the will to excel proved
      to be predictors of investments in deliberate practice. Moreover, achievement
      motivation and chess-specific motivation differed to a certain extent between
      persisters and dropouts. Our results suggest that motivation to engage in
      deliberate practice not only contains elements of the will to improve
      performance, but also of the will to attain exceptional levels of performance.

PMID- 18089894
TI  - A grounded theory of young tennis players use of music to manipulate emotional
      state.
AB  - The main objectives of this study were (a) to elucidate young tennis players' use
      of music to manipulate emotional states, and (b) to present a model grounded in
      present data to illustrate this phenomenon and to stimulate further research.
      Anecdotal evidence suggests that music listening is used regularly by elite
      athletes as a preperformance strategy, but only limited empirical evidence
      corroborates such use. Young tennis players (N = 14) were selected purposively
      for interview and diary data collection. Results indicated that participants
      consciously selected music to elicit various emotional states; frequently
      reported consequences of music listening included improved mood, increased
      arousal, and visual and auditory imagery. The choice of music tracks and the
      impact of music listening were mediated by a number of factors, including
      extramusical associations, inspirational lyrics, music properties, and desired
      emotional state. Implications for the future investigation of preperformance
      music are discussed.

PMID- 18089895
TI  - Development and validation of the moral disengagement in sport scale.
AB  - A sport-specific measure of moral disengagement was developed in 2 studies. In
      Study 1, a 59-item questionnaire was developed and tested with 308 athletes from
      5 team sports. A series of confirmatory factor analyses (CFA) testing different
      models suggested the model that best fitted the data had 6 first-order factors
      that could be represented by 1 second-order factor. Study 2 involved 305 athletes
      from the same 5 sports. CFA confirmed the 6-factor, second-order structure for
      the final 32-item measure. Results from Study 2 supported the construct validity
      of the scale, providing evidence for the factorial, concurrent, convergent, and
      discriminant validity. The Moral Disengagement in Sport Scale (MDSS) is proposed
      as a valid and reliable measure of moral disengagement for use in the sport
      context.

PMID- 18089896
TI  - Self-reported psychological states and physiological responses to different types
      of motivational general imagery.
AB  - The aim of the present study was to examine self-reported psychological states
      and physiological responses (heart rate) experienced during different
      motivational general imagery scenarios. Forty competitive athletes wore a
      standard heart rate monitor and imaged five scripts (mastery, coping, anxiety,
      psyching up, and relaxation). Following each script, they reported their state
      anxiety and self-confidence. A significant increase in heart rate from baseline
      to imagery was found for the anxiety, psyching-up, and coping imagery scripts.
      Furthermore, the intensity of cognitive and somatic anxiety was greater and
      perceived as being more debilitative following the anxiety imagery script. The
      findings support Lang's (1977, 1979) proposal that images containing response
      propositions will produce a physiological response (i.e., increase heart rate).
      Moreover, coping imagery enabled the athletes to simultaneously experience
      elevated levels of anxiety intensity and thoughts and feelings they perceived as
      helpful.

PMID- 18089897
TI  - Testing self-determined motivation as a mediator of the relationship between
      psychological needs and affective and behavioral outcomes.
AB  - Self-determination theory suggests that when psychological needs for autonomy,
      competence, and relatedness are met, participants experience more self-determined
      types of motivation and more positive outcomes. Limited research has examined
      this mediational role of self-determined motivation in adult physical activity
      participants, and very few studies have included assessments of relatedness. This
      study tested the hypothesis that self-determined motivation would mediate the
      relationship between psychological need fulfillment and affective and behavioral
      outcomes. Adult dragon boaters (N = 558) between the ages of 19 and 83 completed
      a questionnaire on motivational aspects of dragon boating. Competence,
      relatedness, and autonomy all significantly predicted self-determined motivation,
      but self-determined motivation only partially mediated their relationship with
      positive and negative affect. These findings demonstrate the importance of all
      three needs in adult activity motivation and suggest that the relationships
      between needs, self-determination, and outcomes may be complex.

PMID- 18089898
TI  - But what do the numbers really tell us? Arbitrary metrics and effect size
      reporting in sport psychology research.
AB  - Many of the measurements used in sport psychology research are arbitrary metrics,
      and researchers often cannot make the jump from scores on paper-and-pencil tests
      to what those scores actually mean in terms of real-world behaviors. Effect sizes
      for behavioral data are often interpretable, but the meaning of a small, medium,
      or large effect for an arbitrary metric is elusive. We reviewed all the issues in
      the 2005 volumes of the Journal of Sport & Exercise Psychology, The Sport
      Psychologist, and the Journal of Applied Sport Psychology to determine whether
      the arbitrary metrics used in sport psychology research were interpreted, or
      calibrated, against real-world variables. Of the 54 studies that used
      quantitative methods, 25 reported only paper-and-pencil arbitrary metrics with no
      connections to behavior or other real-world variables. Also, 44 of the 54 studies
      reported effect sizes, but only 7 studies, using both arbitrary and behavioral
      metrics, had calculated effect indicators and interpreted them in terms of real
      world meaning.

PMID- 18089899
TI  - Cross-lagged relationships among leisure-time exercise and perceived stress in
      blue-collar workers.
AB  - Blue-collar workers (N = 203) from a large food-processing plant in the
      southwestern U.S. completed measures of perceived stress and leisure-time
      exercise at an initial test session in addition to a 2-month follow-up session.
      Mean age of the sample participants equaled 43.61 (SD = 9.79), and 69.5% of the
      sample were male, 71.4% were Caucasian, and 74.9% were married/cohabitating.
      Structural equation modeling was employed to examine the cross-lagged
      relationships between perceived stress and leisure-time exercise at these time
      points, controlling for gender, marital status, age, and yearly household income.
      Results indicated that a model with a path from perceptions of Time 1 stress to
      Time 2 exercise frequency was most parsimonious and provided acceptable model
      fit, suggesting that perceptions of stress are related to reductions in exercise
      participation in this population. However, there was little support for a
      relationship between Time 1 exercise participation and Time 2 perceived stress.

PMID- 18089900
TI  - Exercise makes you feel good, but does feeling good make you exercise?: an
      examination of obese dieters.
AB  - Whereas exercise-induced mood enhancement has been well documented, the
      relationship between mood and exercise participation is less well understood.
      Mood states influence evaluative judgments that could plausibly influence a
      decision to exercise. Further, most exercise-mood research is limited to normal
      weight adults in response to a single exercise session. The current investigation
      examines the influence of (a) morning mood on exercise, (b) exercise
      intensity/duration on mood enhancement, and (c) daily change in mood on exercise
      days compared with nonexercise days in obese behavioral weight loss program
      (BWLP) participants. Participants (N = 36) recorded morning, evening, and pre-and
      postexercise mood, as well as the type, duration, and intensity of exercise.
      Within-person analyses indicated that (a) morning mood was associated with an
      increased likelihood of exercising, (b) mood ratings were higher following
      exercise of greater intensity and duration, and (c) daily mood enhancement was
      associated with greater exercise initiation and greater exercise intensity.
      Measuring mood before and after exercise may yield important clinical information
      that can be used to promote physical activity in obese adults.

PMID- 18089901
TI  - Resistance training and older adults' beliefs about psychological benefits: the
      importance of self-efficacy and social interaction.
AB  - The purpose of this study was to determine the perceived psychological benefits
      and explore the mechanisms underlying the link between exercise and psychological
      well-being for a group of older adults (65-72 years; 6 women; 4 men) who
      participated in a 12-week program of moderate-to-high intensity resistance
      training. They were interviewed in-depth at 1 week preintervention, 1 month after
      commencement, and 1 week after completion. The participants believed that
      resistance training enhanced their well-being, and they gave various physical,
      mental, and social reasons to explain this link. In particular, self-efficacy and
      social interaction were found to be key mechanisms underlying this relationship.
      This study exposed meaningful perceived improvements in psychological wellbeing
      that have not been uncovered in quantitative studies of healthy older people
      undertaking resistance training. The findings highlight the importance of using
      qualitative methods to enrich understandings of the positive effect of exercise
      on psychological well-being. The findings also have implications for designing
      effective resistance training interventions for older people.

PMID- 18089902
TI  - Predictors of poor sportspersonship in youth sports: personal attitudes and
      social influences.
AB  - The present study examined personal and social correlates of poor
      sportspersonship among youth sport participants. Male and female athletes (n =
      676) in the fifth through eighth grades from three geographic regions of the U.S.
      participated in the study. Young athletes involved in basketball, soccer,
      football, hockey, baseball/ softball, or lacrosse completed a questionnaire that
      tapped poor sportspersonship behaviors and attitudes, team sportspersonship
      norms, perceptions of the poor sportspersonship behaviors of coaches and
      spectators, and the sportspersonship norms of coaches and parents. Preliminary
      analyses revealed significant gender, grade, sport area, and location differences
      in self-reported unsportspersonlike behavior. The main analysis revealed that
      self-reported poor sport behaviors were best predicted by perceived coach and
      spectator behaviors, followed by team norms, sportspersonship attitudes, and the
      perceived norms of parents and coaches. Results are discussed in relation to the
      concept of moral atmosphere.

PMID- 18089903
TI  - Goal striving, goal attainment, and well-being: adapting and testing the self
      concordance model in sport.
AB  - Grounded in self-determination theory (Deci & Ryan, 1985) and the self
      concordance model (Sheldon & Elliot, 1999), this study examined the motivational
      processes underlying goal striving in sport as well as the role of perceived
      coach autonomy support in the goal process. Structural equation modeling with a
      sample of 210 British athletes showed that autonomous goal motives positively
      predicted effort, which, in turn, predicted goal attainment. Goal attainment was
      positively linked to need satisfaction, which, in turn, predicted psychological
      well-being. Effort and need satisfaction were found to mediate the associations
      between autonomous motives and goal attainment and between attainment and well
      being, respectively. Controlled motives negatively predicted well-being, and
      coach autonomy support positively predicted both autonomous motives and need
      satisfaction. Associations of autonomous motives with effort were not reducible
      to goal difficulty, goal specificity, or goal efficacy. These findings support
      the self-concordance model as a framework for further research on goal setting in
      sport.

PMID- 18089904
TI  - Exercise and working memory: an individual differences investigation.
AB  - In the current work we asked whether executive function, as measured by tests of
      working memory capacity, might benefit from an acute bout of exercise and, more
      specifically, whether individuals who are lower or higher in working memory to
      begin with would be more or less affected by an exercise manipulation. Healthy
      adults completed working memory measures in a nonexercise (baseline) session and
      immediately following a 30-min self-paced bout of exercise on a treadmill
      (exercise session). Sessions were conducted 1 week apart and session order was
      counterbalanced across participants. A significant Session x Working Memory
      interaction was obtained such that only those individuals lowest in working
      memory benefited from the exercise manipulation. This work suggests that acute
      bouts of exercise may be most beneficial for healthy adults whose cognitive
      performance is generally the lowest, and it demonstrates that the impact of
      exercise on cognition is not uniform across all individuals.

PMID- 18089905
TI  - Effects of caffeine on physiological responses to exercise: boys versus men.
AB  - We compared the influence of caffeine on physiological responses to exercise
      between boys and men. Fifty-two participants (26 boys and 26 men) participated in
      a double blind, randomized, double crossover study. Each participant received the
      caffeinated (5 mg/kg) drink (CAF) and placebo (PL) twice each on 4 separate days.
      One hour after drink consumption preexercise heart rate (HR) and blood pressure
      (BP) were measured. Then while the participants rode stationary cycle ergometers
      at two different exercise intensities, HR, BP, and oxygen consumption (VO2) were
      measured. Blood pressure was not significantly affected by CAF, although on
      average it was always higher in boys for diastolic BP (3 mmHg) and systolic BP (3
      4 mmHg) and men for diastolic BP (2-3 mmHg) and systolic BP (1-6 mmHg) both at
      rest and during exercise. HR was significantly (p < .05) lower at rest, 25W and
      50W in CAF versus PL in boys, with no change in adults. During exercise, VO2 and
      respiratory exchange ratio (RER) were not different in CAF versus PL in either
      group. In conclusion, metabolism is not affected by a moderate caffeine dose in
      children or adults. The same dose has a similar effect on BP in both groups. The
      effect on HR was different, however, with a significant (p < .05) lowering in
      children in CAF versus PL, with no adult effects.

PMID- 18089906
TI  - Maturity-related differences in physical activity among 13- to 14-year-old
      adolescents.
AB  - The age-related decline in physical activity during adolescence is well
      documented; however, little is known about differences in physical activity among
      early, average, and late maturing adolescents. The purpose of this study was to
      examine the relationship between maturity status and physical activity among 167
      adolescents who were 13-14 years old. The maturity offset was derived and
      biological maturity groups were created. Habitual physical activity was
      determined with a pedometer over a 7-day period. No significant maturity-group
      differences were found for physical activity. The results of this study did not
      demonstrate significant differences in physical activity as determined by a
      pedometer among early, average, and late maturing 13- to 14-year-olds.

PMID- 18089907
TI  - Activity levels, dietary energy intake, and body composition in children who walk
      to school.
AB  - Although differences in daily activity levels have been assessed in cross
      sectional walk-to-school studies, no one has assessed differences in body
      composition and dietary energy intake at the same time. In this study of 239
      primary school children, there were no significant differences in daily activity
      levels, body composition, or estimated dietary energy intake between those who
      walk to school (WALK) and those who travel by car (CAR; p < .05). WALK children
      were more active between 8 a.m. and 9 a.m. and 3 p.m. and 4 p.m. than CAR
      children (p < .05). In addition, there were no significant differences in the
      main analysis when participants were subgrouped by gender and age.

PMID- 18089908
TI  - Exercise training and cardiovascular risk factors in type 1 diabetic adolescent
      girls.
AB  - Sixteen postmenarcheal Type 1 diabetic adolescent girls were randomized into
      training (involving aerobic and strength exercises) and nontraining groups. Body
      composition (skinfold thickness), aerobic fitness (PWC170), plasma lipids, serum
      apolipoproteins, lipoprotein(a), leptin, and adiponectin were assessed before and
      after the 6-month period. After the 6-month period, fat mass and leptin increased
      significantly in the nontraining group but not in the training group. Conversely,
      in the latter group, fat-free mass increased (P < .01). Moreover, PWC170 improved
      and apolipoproteinB:apolipoproteinA-1 ratio decreased with physical training (P <
      .05). Thus, physical training reduces cardiovascular risks and the increase of
      insulin resistance risk factors in diabetic adolescent girls.

PMID- 18089909
TI  - Investigating the youth physical activity promotion model: internal structure and
      external validity evidence for a potential measurement model.
AB  - The purpose of the study was to investigate the measurement properties of
      questionnaires associated with the Youth Physical Activity Promotion (YPAP)
      model. Data were collected from 296 children in Grades 5-8 using several existing
      questionnaires corresponding to YPAP model components, a physical activity
      questionnaire, and 6 consecutive days of pedometer data. Internal validity of the
      questionnaires was tested using confirmatory factor analyses, and external
      validity was investigated via correlations with physical activity and body
      composition. Initial model fit of the questionnaires ranged from poor to very
      good. After item removal, all scales demonstrated good fit. Correlations with
      percentage body fat and objectively measured physical activity were low but in
      the theoretically predicted direction. The current study provides good internal
      validity evidence and acceptable external validity evidence for a brief set of
      questionnaire items to investigate the theoretical basis for the YPAP model.

PMID- 18089910
TI  - Active transport to school as part of a broader habit of walking and cycling
      among South Australian youth.
AB  - This study examined whether active commuting to and from school was associated
      with more frequent walking and cycling to other neighborhood destinations.
      Parents reported on free-time physical activity and frequency of active commuting
      among 1,643 South Australians (9-15 years), as well as their perceptions of risk
      associated with active commuting in the neighborhood. Groups were formed on the
      basis of active and motorized transport to and from school and compared on the
      frequency of walking and cycling to other neighborhood destinations. Those who
      actively commuted between home and school were approximately 30% more likely to
      actively commute to other neighborhood destinations, independent of age, free
      time physical activity, and neighborhood risk. Active commuting to and from
      school is part of a broader habit of walking and cycling in the neighborhood
      among school age South Australians. The advantages of promoting active transport
      between home and school might extend beyond the energy expenditure of that
      journey alone.

PMID- 18089911
TI  - Estrogen receptor alpha polymorphism modifies the association between childhood
      exercise and bone mass: follow-up study.
AB  - This follow-up study confirms our previous findings that the ER-alpha PvuII
      polymorphism (Pp) modulates the association between exercise and bone mass. The
      differences in bone properties of girls with consistently low physical activity
      (LLPA) and consistently high physical activity (HHPA) were evident only in those
      bearing the heterozygote ER-alpha genotype (Pp). In particular, areal bone
      mineral density of the total femur, bone mineral content and areal bone mineral
      density of the femoral neck, and bone mineral content and cortical thickness of
      the tibia shaft were significantly (p < .05) lower in the Pp girls with LLPA than
      in their HHPA counterparts. These findings might partly explain the genetic basis
      of human variation associated with exercise training.

PMID- 18089912
TI  - Effect of screen-based media on energy expenditure and heart rate in 9- to 12
      year-old children.
AB  - This study compared the cardiovascular responses and energy costs of new and
      traditional screen based entertainments, as played by twenty 9- to 12-year-old
      children. Playing traditional electronic games resulted in little change to heart
      rate or energy expenditure compared with watching a DVD. In contrast, playing an
      active-input game resulted in a 59% increase in heart rate (p < .001) and a 224%
      increase in energy expenditure (p < .001) for boys and girls. The average heart
      rate of 130 bpm and energy expenditure of 0.13 kcal . min-1 . kg-1 achieved
      during active-input game use equates with moderate intensity activities such as
      basketball and jogging. Active-input electronic games might provide children with
      opportunities to engage with technology and be physically active at the same
      time.

PMID- 18089913
TI  - Maturational differences in physical self- perceptions and the relationship with
      physical activity in early adolescent girls.
AB  - This cross-sectional study examined the relationship between physical self
      perceptions (PSPs), maturation, and physical activity and compared the strength
      of the relationships of biological and chronological age with PSPs in early
      adolescent girls (N = 208; mean age = 11.83 +/- 0.39 years). Participants
      completed the Physical Activity Questionnaire for Older Children, the Children's
      Physical Self-Perception Profile, and the Pubertal Development Scale. Results
      indicated that PSPs were significantly and moderately correlated with physical
      activity. There were no differences in physical activity between maturation
      stages. Girls who were in the early stages of maturation had significantly more
      positive perceptions of body attractiveness and physical self-worth than girls in
      the mid stages of maturation. There was no evidence of a relationship between
      PSPs and chronological age. This study provided further support for the
      relationship between PSPs and physical activity and the relationship between
      maturation and aspects of PSPs. In this age group, maturation does not appear to
      be related to physical activity or the PSPs most strongly influential on physical
      activity behavior.

PMID- 18089914
TI  - The influence of gender and somatotype on single-leg upright standing postural
      stability in children.
AB  - The purpose of this study was to investigate the influence of gender and
      somatotypes on single-leg upright standing postural stability in children. A
      total of 709 healthy children from different schools were recruited to measure
      the anthropometric somatotypes and the mean radius of center of pressure (COP) on
      a force platform with their eyes open and eyes closed. The results were that (a)
      girls revealed significantly smaller mean radius of COP distribution than boys,
      both in the eyes open and eyes closed conditions, and (b) the mesomorphic,
      muscular children had significantly smaller mean radius of COP distribution than
      the endomorphic, fatty children and the ectomorphic, linear children during the
      eyes closed condition. The explanation for gender differences might be due to the
      larger body weight in boys. The explanation for somatotype differences might be
      due to the significantly lower body height and higher portion of muscular profile
      in the mesomorphic children.

PMID- 18089915
TI  - Correlation between ground reaction force and tibial acceleration in vertical
      jumping.
AB  - Modern electronics allow for the unobtrusive measurement of accelerations outside
      the laboratory using wireless sensor nodes. The ability to accurately measure
      joint accelerations under unrestricted conditions, and to correlate them with
      jump height and landing force, could provide important data to better understand
      joint mechanics subject to real-life conditions. This study investigates the
      correlation between peak vertical ground reaction forces, as measured by a force
      plate, and tibial axial accelerations during free vertical jumping. The jump
      heights calculated from force-plate data and accelerometer measurements are also
      compared. For six male subjects participating in this study, the average
      coefficient of determination between peak ground reaction force and peak tibial
      axial acceleration is found to be 0.81. The coefficient of determination between
      jump height calculated using force plate and accelerometer data is 0.88. Data
      show that the landing forces could be as high as 8 body weights of the jumper.
      The measured peak tibial accelerations ranged up to 42 g. Jump heights calculated
      from force plate and accelerometer sensors data differed by less than 2.5 cm. It
      is found that both impact accelerations and landing forces are only weakly
      correlated with jump height (the average coefficient of determination is 0.12).
      This study shows that unobtrusive accelerometers can be used to determine the
      ground reaction forces experienced in a jump landing. Whereas the device also
      permitted an accurate determination of jump height, there was no correlation
      between peak ground reaction force and jump height.

PMID- 18089916
TI  - Gender and bilateral differences in single-leg countermovement jump performance
      with comparison to a double-leg jump.
AB  - Expectations may be for both legs to function identically during single- and
      double-leg vertical jumps. However, several reasons might prevent this from
      occurring. The goals of this investigation were twofold: assess the presence of
      side-to-side jump height differences during single-leg jumps in a homogenous
      group of healthy subjects and determine if those with a jump height asymmetry
      possessed consistent biomechanical differences during single-and double-leg
      jumps. Thirteen men and 12 women with competitive volleyball experience
      volunteered for the study. Significance was assessed at p < 0.05. The men jumped
      significantly higher than the women in all conditions and possessed differences
      in several anthropometric, kinematic, and kinetic parameters. Based on a three
      jump average, all subjects had one leg that they could jump higher with (the
      dominant leg, DL). The men generated significantly greater maximum ground
      reaction forces and ankle joint powers on their DL whereas the women had no
      differences during the single-leg jumps. The only side-to-side differences that
      existed during the double-leg jumps were in the average ground reaction forces
      during propulsion. These findings suggest that equality of single-leg jump
      performance is the exception rather than the norm, with identification of
      consistent biomechanical attributes difficult within a group.

PMID- 18089917
TI  - The correlation of segment accelerations and impact forces with knee angle in
      jump landing.
AB  - Impact forces and shock deceleration during jumping and running have been
      associated with various knee injury etiologies. This study investigates the
      influence of jump height and knee contact angle on peak ground reaction force and
      segment axial accelerations. Ground reaction force, segment axial acceleration,
      and knee angles were measured for 6 male subjects during vertical jumping. A
      simple spring-mass model is used to predict the landing stiffness at impact as a
      function of (1) jump height, (2) peak impact force, (3) peak tibial axial
      acceleration, (4) peak thigh axial acceleration, and (5) peak trunk axial
      acceleration. Using a nonlinear least square fit, a strong (r = 0.86) and
      significant (p < or = 0.05) correlation was found between knee contact angle and
      stiffness calculated using the peak impact force and jump height. The same model
      also showed that the correlation was strong (r = 0.81) and significant (p < or =
      0.05) between knee contact angle and stiffness calculated from the peak trunk
      axial accelerations. The correlation was weaker for the peak thigh (r = 0.71) and
      tibial (r = 0.45) axial accelerations. Using the peak force but neglecting jump
      height in the model, produces significantly worse correlation (r = 0.58). It was
      concluded that knee contact angle significantly influences both peak ground
      reaction forces and segment accelerations. However, owing to the nonlinear
      relationship, peak forces and segment accelerations change more rapidly at
      smaller knee flexion angles (i.e., close to full extension) than at greater knee
      flexion angles.

PMID- 18089918
TI  - The validity of ultrasound estimation of muscle volumes.
AB  - The purpose of this study was to validate ultrasound muscle volume estimation in
      vivo. To examine validity, vastus lateralis ultrasound images were collected from
      cadavers before muscle dissection; after dissection, the volumes were determined
      by hydrostatic weighing. Seven thighs from cadaver specimens were scanned using a
      7.5-MHz ultrasound probe (SSD-1000, Aloka, Japan). The perimeter of the vastus
      lateralis was identified in the ultrasound images and manually digitized. Volumes
      were then estimated using the Cavalieri principle, by measuring the image areas
      of sets of parallel two-dimensional slices through the muscles. The muscles were
      then dissected from the cadavers, and muscle volume was determined via
      hydrostatic weighing. There was no statistically significant difference between
      the ultrasound estimation of muscle volume and that estimated using hydrostatic
      weighing (p > 0.05). The mean percentage error between the two volume estimates
      was 0.4% +/- 6.9. Three operators all performed four digitizations of all images
      from one randomly selected muscle; there was no statistical difference between
      operators or trials and the intraclass correlation was high (>0.8). The results
      of this study indicate that ultrasound is an accurate method for estimating
      muscle volumes in vivo.

PMID- 18089919
TI  - A simple method to obtain consistent and clinically meaningful pelvic angles from
      euler angles during gait analysis.
AB  - Clinical gait analysis usually describes joint kinematics using Euler angles,
      which depend on the sequence of rotation. Studies have shown that pelvic
      obliquity angles from the traditional tilt-obliquity-rotation (TOR) Euler angle
      sequence can deviate considerably from clinical expectations and have suggested
      that a rotation-obliquity-tilt (ROT) Euler angle sequence be used instead. We
      propose a simple alternate approach in which clinical joint angles are defined
      and exactly calculated in terms of Euler angles from any rotation sequence.
      Equations were derived to calculate clinical pelvic elevation, progression, and
      lean angles from TOR and ROT Euler angles. For the ROT Euler angles, obliquity
      was exactly the same as the clinical elevation angle, rotation was similar to the
      clinical progression angle, and tilt was similar to the clinical lean angle.
      Greater differences were observed for TOR. These results support previous
      findings that ROT is preferable to TOR for calculating pelvic Euler angles for
      clinical interpretation. However, we suggest that exact clinical angles can and
      should be obtained through a few extra calculations as demonstrated in this
      technical note.

PMID- 18089920
TI  - A low-cost instrumented spatial linkage accurately determines ASIS position
      during cycle ergometry.
AB  - The purpose of this study was to develop and evaluate an alternative method for
      determining the position of the anterior superior iliac spine (ASIS) during
      cycling. The approach used in this study employed an instrumented spatial linkage
      (ISL) system to determine the position of the ASIS in the parasagittal plane. A
      two-segment ISL constructed using aluminum segments, bearings, and digital
      encoders was tested statically against a calibration plate and dynamically
      against a video-based motion capture system. Four well-trained cyclists provided
      data at three pedaling rates. Statically, the ISL had a mean horizontal error of
      0.03 +/- 0.21 mm and a mean vertical error of -0.13 +/- 0.59 mm. Compared with
      the video-based motion capture system, the agreement of the location of the ASIS
      had a mean error of 0.30 +/- 0.55 mm for the horizontal dimension and -0.27 +/-
      0.60 mm for the vertical dimension. The ISL system is a cost-effective, accurate,
      and valid measure for two-dimensional kinematic data within a range of motion
      typical for cycling.

PMID- 18089921
TI  - Computational determination of the critical microcrack size that causes a
      remodeling response in a trabecula: a feasibility study.
AB  - Bone is a living tissue, which undergoes continuous renewal to repair local
      defects. Two separate processes, adaptation and remodeling, are involved when a
      defect appears. The defect produces stress concentrations that provoke regional
      adaptation, and is gradually repaired, first by resorption and then by deposition
      of new bone. Using a mathematical formulation of the adaptation mechanism in
      trabeculae of cancellous bone, we hypothesize that in some cases, where a
      microcrack is small enough relative to the dimensions of the trabecula, the
      adaptation response of the whole trabecula may be sufficient to regain
      homeostatic mechanical conditions (with no need for a remodeling process). The
      simulation results showed that for trabeculae with nominal length of 900 microm
      and nominal thickness of 80-800 microm, a microcrack with minimal length of 48
      microm and minimal depth of 13% of the trabecula's thickness was required to
      initiate a remodeling process. A longer (100 microm) but shallower (depth of 7%
      of the trabecula's thickness) crack also triggered remodeling. These
      computational results support our hypothesis that when a microcrack small enough
      relative to the dimensions of the trabecula occurs, adaptation of the whole
      trabecula may be sufficient to regain homeostatic mechanical conditions with no
      need for a local remodeling process.

PMID- 18089922
TI  - Validation of a noninvasive system for measuring head acceleration for use during
      boxing competition.
AB  - Although the epidemiology and mechanics of concussion in sports have been
      investigated for many years, the biomechanical factors that contribute to mild
      traumatic brain injury remain unclear because of the difficulties in measuring
      impact events in the field. The purpose of this study was to validate an
      instrumented boxing headgear (IBH) that can be used to measure impact severity
      and location during play. The instrumented boxing headgear data were processed to
      determine linear and rotational acceleration at the head center of gravity,
      impact location, and impact severity metrics, such as the Head Injury Criterion
      (HIC) and Gadd Severity Index (GSI). The instrumented boxing headgear was fitted
      to a Hybrid III (HIII) head form and impacted with a weighted pendulum to
      characterize accuracy and repeatability. Fifty-six impacts over 3 speeds and 5
      locations were used to simulate blows most commonly observed in boxing. A high
      correlation between the HIII and instrumented boxing headgear was established for
      peak linear and rotational acceleration (r2= 0.91), HIC (r2 = 0.88), and GSI (r2
      = 0.89). Mean location error was 9.7 +/- 5.2 masculine. Based on this study, the
      IBH is a valid system for measuring head acceleration and impact location that
      can be integrated into training and competition.

PMID- 18089924
TI  - Postural preparation to making a step: is there a 'motor program' for postural
      preparation?
AB  - We tested the hypothesis that a sequence of mechanical events occurs preceding a
      step that scales in time and magnitude as a whole in a task-specific manner, and
      is a reflection of a "motor program." Young subjects made a step under three
      speed instructions and four tasks: stepping straight ahead, down a stair, up a
      stair, and over an obstacle. Larger center-of-pressure (COP) and force
      adjustments in the anterior-posterior direction and smaller COP and force
      adjustments in the mediolateral direction were seen during stepping forward and
      down a stair, as compared with the tasks of stepping up a stair and over an
      obstacle. These differences were accentuated during stepping under the simple
      reaction time instruction. These results speak against the hypothesis of a single
      motor program that would underlie postural preparation to stepping. They are more
      compatible with the reference configuration hypothesis of whole-body actions.

PMID- 18089923
TI  - Diabetic neuropathy is related to joint stiffness during late stance phase.
AB  - The majority of plantar ulcers in the diabetic population occur in the forefoot.
      Peripheral neuropathy has been related to the occurrence of ulcers. Long-term
      diabetes results in the joints becoming passively stiffer. This static stiffness
      may translate to dynamic joint stiffness in the lower extremities during gait.
      Therefore, the purpose of this investigation was to demonstrate differences in
      ankle and knee joint stiffness between diabetic individuals with and without
      peripheral neuropathy during gait. Diabetic subjects with and without peripheral
      neuropathy were compared. Subjects were monitored during normal walking with
      three-dimensional motion analysis and a force plate. Neuropathic subjects had
      higher ankle stiffness (0.236 N.m/deg) during 65 to 80% of stance when compared
      with non-neuropathic subjects (-0.113 N.m/deg). Neuropathic subjects showed a
      different pattern in ankle stiffness compared with non-neuropathic subjects.
      Neuropathic subjects demonstrated a consistent level of ankle stiffness, whereas
      non-neuropathic subjects showed varying levels of stiffness. Neuropathic subjects
      demonstrated lower knee stiffness (0.015 N.m/deg) compared with non-neuropathic
      subjects (0.075 N.m/deg) during 50 to 65% of stance. The differences in patterns
      of ankle and knee joint stiffness between groups appear to be related to changes
      in timing of peak ankle dorsiflexion during stance, with the neuropathic group
      reaching peak dorsiflexion later than the non-neuropathic subjects. This may
      partially relate to the changes in plantar pressures beneath the metatarsal heads
      present in individuals with neuropathy.

PMID- 18089925
TI  - The effect of a knee support on the biomechanical response of the low back.
AB  - Stooping and squatting postures are seen in a number of industries (e.g.,
      agriculture, construction) where workers must work near ground level for extended
      periods of time. The focus of the current research was to evaluate a knee support
      device designed to reduce the biomechanical loading of these postures. Ten
      participants performed a series of sudden loading tasks while in a semisquat
      posture under two conditions of knee support (no support and fully supported) and
      two conditions of torso flexion (45 and 60 degrees ). A weight was released into
      the hands of the participants who then came to steady state while maintaining the
      designated posture. As they performed this task, the EMG responses of the trunk
      extensors (multifidus and erector spinae) were collected, both during the "sudden
      loading" phase of the trial as well as the steady weight-holding phase of the
      trial. As expected, the effects of torso flexion angle showed significant
      decreases in the activation of the multifidus muscles with greater torso angle
      (indicating the initiation of the flexion-relaxation response). Interestingly,
      the results showed that the knee support device had no effect on the activation
      levels of the sampled muscles, indicating that the loss of the degree of freedom
      from the ankle joint during the knee support condition had no impact on trunk
      extensor muscle response. The a priori concern with regard to these supports was
      that they would tend to focus loading on the low back and therefore would not
      serve as a potential ergonomic solution for these stooping/semisquatting tasks.
      Because the results of this study did not support this concern, further
      development of such an intervention is underway.

PMID- 18089926
TI  - Mechanical properties of chest protectors and the likelihood of ventricular
      fibrillation due to commotio cordis.
AB  - Sudden death resulting from ventricular fibrillation (VF) caused by a
      nonpenetrating chest wall impact, known as commotio cordis (CC), is the second
      leading cause of death among young athletes. To date, seven young athletes
      wearing chest protectors have died from CC. The purpose of this study was to
      determine whether a relationship exists between mechanical properties of chest
      protectors and occurrence of VF, previously determined by Weinstock et al., using
      an established swine model. A servo-hydraulic material tester was used to
      determine properties of the chest protectors, including displacement, permanent
      deformation, stiffness, and area of pressure distribution. These properties were
      then compared with the occurrence of VF. We found that a decreased proportion of
      hits resulting in VF was significantly associated (R2 = 0.59, p = 0.001) with an
      increase in the area of pressure distribution. These findings are a limited, but
      crucial, first step in understanding the prevention of this complex and
      perplexing phenomenon.

PMID- 18089927
TI  - Effects of gender and foot-landing techniques on lower extremity kinematics
      during drop-jump landings.
AB  - The purpose of this study was to assess kinematic lower extremity motion patterns
      (hip flexion, knee flexion, knee valgus, and ankle dorsiflexion) during various
      foot-landing techniques (self-preferred, forefoot, and rear foot) between
      genders. 3-D kinematics were collected on 50 (25 male and 25 female) college-age
      recreational athletes selected from a sample of convenience. Separate repeated
      measures ANOVAs were used to analyze each variable at three time instants
      (initial contact, peak vertical ground reaction force, and maximum knee flexion
      angle). There were no significant differences found between genders at the three
      instants for each variable. At initial contact, the forefoot technique (35.79
      degrees +/- 11.78 degrees ) resulted in significantly (p = .001) less hip flexion
      than did the self-preferred (41.25 degrees +/- 12.89 degrees ) and rear foot
      (43.15 degrees +/- 11.77 degrees ) techniques. At peak vertical ground reaction
      force, the rear foot technique (26.77 degrees +/- 9.49 degrees ) presented
      significantly lower (p = .001) knee flexion angles as compared with forefoot
      (58.77 degrees +/- 20.00 degrees ) and self-preferred (54.21 degrees +/- 23.78
      degrees ) techniques. A significant difference for knee valgus angles (p = .001)
      was also found between landing techniques at peak vertical ground reaction force.
      The self-preferred (4.12 degrees +/- 7.51 degrees ) and forefoot (4.97 degrees +/
      7.90 degrees ) techniques presented greater knee varus angles as compared with
      the rear foot technique (0.08 degrees +/- 6.52 degrees ). The rear foot technique
      created more ankle dorsiflexion and less knee flexion than did the other
      techniques. The lack of gender differences can mean that lower extremity injuries
      (e.g., ACL tears) may not be related solely to gender but may instead be
      associated with the landing technique used and, consequently, the way each
      individual absorbs jump-landing energy.

PMID- 18089928
TI  - Optimization of backward giant circle technique on the asymmetric bars.
AB  - The release window for a given dismount from the asymmetric bars is the period of
      time within which release results in a successful dismount. Larger release
      windows are likely to be associated with more consistent performance because they
      allow a greater margin for error in timing the release. A computer simulation
      model was used to investigate optimum technique for maximizing release windows in
      asymmetric bars dismounts. The model comprised four rigid segments with the
      elastic properties of the gymnast and bar modeled using damped linear springs.
      Model parameters were optimized to obtain a close match between simulated and
      actual performances of three gymnasts in terms of rotation angle (1.5 degrees ),
      bar displacement (0.014 m), and release velocities (<1%). Three optimizations to
      maximize the release window were carried out for each gymnast involving no
      perturbations, 10-ms perturbations, and 20-ms perturbations in the timing of the
      shoulder and hip joint movements preceding release. It was found that the
      optimizations robust to 20-ms perturbations produced release windows similar to
      those of the actual performances whereas the windows for the unperturbed
      optimizations were up to twice as large. It is concluded that robustness
      considerations must be included in optimization studies in order to obtain
      realistic results and that elite performances are likely to be robust to timing
      perturbations of the order of 20 ms.

PMID- 18089929
TI  - Fusion integration: COM trajectory from a force platform.
AB  - A fusion integration algorithm is used to estimate the one-dimensional center of
      mass (COM) trajectory from force platform data. The resulting COM trajectory
      combines the best attributes of several established algorithms used to estimate
      the COM trajectory, and it appears to have the advantage of being robust,
      accurate, continuous in its higher derivatives, and fast to obtain. In current
      research projects, variations of the fusion integration algorithm have been
      adapted by the authors for the analysis of postural balance and the sensing of
      limb orientations with inertial measurement units.

PMID- 18089930
TI  - Effects of finger markers on the kinematics of reaching movements in young
      children and adults.
AB  - Kinematic studies to date have not considered in what ways surface markers may
      affect the performance of the analyzed motion. This neglect is particularly
      apparent in studies of prehensile movements involving surface markers attached to
      the fingers. In order to specify any such effects, a range of kinematic
      parameters derived from simple reach-to-grasp movements, both with and without
      finger markers, by 3-year old children and adults were analyzed. Finger markers
      affected both the spatial and temporal nature of the children's reaching
      performance as revealed by a more temporally segmented reaching path, an age
      atypically straighter reaching path, and an increased time to establish a pincer
      grip. The reaching movements made by the adults were unaffected in terms of the
      kinematic parameters employed.

PMID- 18089931
TI  - Ground reaction forces during human locomotion on railroad ballast.
AB  - Locomotion over ballast surfaces provides a unique situation for investigating
      the biomechanics of gait. Although much research has focused on level and sloped
      walking on a smooth, firm surface in order to understand the common kinematic and
      kinetic variables associated with human locomotion, the literature currently
      provides few if any discussions regarding the dynamics of locomotion on surfaces
      that are either rocky or uneven. The purpose of this study was to investigate a
      method for using force plates to measure the ground reaction forces (GRFs) during
      gait on ballast. Ballast is a construction aggregate of unsymmetrical rock used
      in industry for the purpose of forming track bed on which railway ties are laid
      or in yards where railroad cars are stored. It is used to facilitate the drainage
      of water and to create even running surfaces. To construct the experimental
      ballast surfaces, 31.75 mm (1 1/4 in.) marble ballast at depths of approximately
      63.5 mm (2.5 in.) or 101.6 mm (4 in.) were spread over a carpeted vinyl tile
      walkway specially designed for gait studies. GRF magnitudes and time histories
      from a force plate were collected under normal smooth surface and under both
      ballast surface conditions for five subjects. GRF magnitudes and time histories
      during smooth surface walking were similar to GRF magnitudes and time histories
      from the two ballast surface conditions. The data presented here demonstrate the
      feasibility of using a force plate system to expand the scope of biomechanical
      analyses of locomotion on ballast surfaces.

PMID- 18089932
TI  - Selective fibrinogen apheresis for improvement in microvascular hemodynamics.

PMID- 18089933
TI  - Serum levels of pigmentation markers are elevated in patients undergoing
      hemodialysis.
AB  - BACKGROUND: Diffuse hyperpigmentation is common among patients with chronic renal
      failure undergoing hemodialysis (HD). We have examined serum levels of 5-S
      cysteinyldopa (5SCD, a pheomelanin precursor), pheomelanin, eumelanin, and
      protein-bound (PB-) 3,4-dihydroxyphenylalanine (DOPA) and PB-5SCD in HD patients.
      METHODS: Pheomelanin and eumelanin were assayed by chemical degradation methods.
      RESULTS: Serum levels of free 5SCD in HD patients (n = 16) were 9-fold higher
      than in healthy controls (n = 16). Levels of pheomelanin in HD patients were 2.6
      fold higher than in controls, while levels of eumelanin did not differ between HD
      patients and controls. Levels of PB-DOPA and PB-5SCD in HD patients were
      approximately 1.5-fold higher than in controls. Serum levels of free 5SCD were
      positively correlated to the duration of HD therapy. CONCLUSIONS: The high
      constitutive levels of free 5SCD, pheomelanin, and PB-DOPA in the blood may be
      deteriorating in HD patients through the production of reactive oxygen species.

PMID- 18089934
TI  - Analysis of the respiratory chain in Ethanologenic Zymomonas mobilis with a
      cyanide-resistant bd-type ubiquinol oxidase as the only terminal oxidase and its
      possible physiological roles.
AB  - The respiratory chain of the ethanologenic bacterium Zymomonas mobilis was
      investigated, in which the pyruvate-to-ethanol pathway has been demonstrated to
      be mainly responsible for NADH oxidation and the tricarboxylic acid cycle is
      incomplete. Membranes from cells cultivated under aerobic or anaerobic growth
      conditions showed dehydrogenase and oxidase activities for NADH, D-lactate and D
      glucose and ubiquinol oxidase activity. Intriguingly, the NADH oxidase activity
      level of membrane fractions from cells grown aerobically was found to be higher
      than that of membrane fractions from Escherichia coli or Pseudomonas putida grown
      aerobically, indicating a crucial role of the respiratory chain in NADH oxidation
      in the organism. Cyanide-resistant terminal oxidase activity was observed and
      appeared to be due to a bd-type ubiquinol oxidase as the only terminal oxidase
      encoded by the entire genome. The terminal oxidase with a relatively strong
      ubiquinol oxidase activity exhibited remarkably weak signals of cytochrome d.
      Considering these findings and the presence of a type-II NADH dehydrogenase but
      not a type-I, a simple respiratory chain that generates less energymay have
      evolved in Z. mobilis.

PMID- 18089936
TI  - Is fiber-type composition related to daily jaw muscle activity during postnatal
      development?
AB  - AIM: Muscles containing large numbers of slow-contracting fibers are generally
      more active than muscles largely composed of fast fibers. This relationship
      between muscle activity and phenotype suggests that (1) changes in fiber-type
      composition during postnatal development are accompanied by changes in daily
      activity and (2) individual variations in fiber-type composition are related to
      similar variations in daily muscle activity. METHODS: The masseter and digastric
      muscles of 23 New Zealand White rabbits (young, juvenile and adult) were examined
      for their phenotype (myosin heavy chain content) and their daily activity (total
      daily number of activity bursts). RESULTS: During development, the masseter
      showed a strong increase in the number of fast-type fibers compared to the number
      of slow-type fibers. During development, also the number of powerful bursts in
      the masseter increased. The digastric showed no significant changes in fiber
      types or burst numbers. Within each muscle, across individual animals, no
      significant correlations (R < 0.70) were found between any of the fiber types and
      daily burst numbers in any of the age groups. CONCLUSIONS: The results suggest
      that activity-related influences are of relatively minor importance during
      development and that other factors are dominant in determining fiber-type
      composition.

PMID- 18089935
TI  - Dynamic analysis of the expression of the TGFbeta/SMAD2 pathway and CCN2/CTGF
      during early steps of tooth development.
AB  - BACKGROUND/AIMS: CCN2 is present during tooth development. However, the
      relationship between CCN2 and the transforming growth factor beta
      (TGFbeta)/SMAD2/3 signaling cascade during early stages of tooth development is
      unclear. Here, we compare the expression of CCN2 and TGFbeta/SMAD2/3 components
      during tooth development, and analyze the functioning of TGFbeta/SMAD2/3 in wild
      type (WT) and Ccn2 null (Ccn2-/-) mice. METHODS: Coronal sections of mice on
      embryonic day (E)11.5, E12.5, E13.5, E14.5 and E18.5 from WT and Ccn2-/- were
      immunoreacted to detect CCN2 and components of the TGFbeta signaling pathway and
      assayed for 5'-bromo-2'-deoxyuridine immunolabeling and proliferating cell
      nuclear antigen immunostaining. RESULTS: CCN2 and TGFbeta signaling components
      such as TGFbeta1, TGFbeta receptor II, SMADs2/3 and SMAD4 were expressed in
      inducer tissues during early stages of tooth development. Proliferation analysis
      in these areas showed that epithelial cells proliferate less than mesenchymal
      cells from E11.5 to E13.5, while at E14.5 they proliferate more than mesenchymal
      cells. We did not find a correlation between functioning of the TGFbeta1 cascade
      and CCN2 expression because Ccn2-/- mice showed neither a reduction in SMAD2
      phosphorylation nor a difference in cell proliferation. CONCLUSION: CCN2 and the
      TGFbeta/SMAD2/3 signaling pathway are active in signaling centers of tooth
      development where proliferation is dynamic, but these mechanisms may act
      independently.

PMID- 18089937
TI  - Cardiac arrest following pneumonectomy.

PMID- 18089938
TI  - Selective IgM deficiency accompanied with IgG4 deficiency, dermal complications
      and a bronchial polyp.
AB  - BACKGROUND: IgM deficiency is a rare primary immunodeficiency. As few studies of
      selective IgM deficiency have been reported among the various other types of
      primary immunodeficiencies, the detailed pathogenesis of this disorder remains to
      be elucidated. CASE SUMMARY: We clinically analyzed a 37-year-old woman who
      presented with IgM and IgG4 deficiency and ectopic bronchial pneumonia, and
      investigated immunological functions. Occlusive pneumonia was repeatedly observed
      in the right S6 area, and bronchoscopy revealed a polyp in the right B6 orifice,
      which was later identified as a fibroepithelial polyp after transbronchial
      endoscopic polypectomy. Two months later, pneumonia involving the right inferior
      lobe developed. Systemic erythema and pigmentation with bleb formation were also
      observed on the skin, and were thought to be drug-induced exanthema following a
      biopsy. Serum levels of IgM and IgG4 were extremely low at 3.0mg/dl and less than
      2.0mg/dl, respectively. Circulating CD20 positive B cells were mildly reduced and
      memory B cells were markedly decreased. The majority of B cells expressed IgM on
      their surface. There were no abnormalities in cell counts of neutrophils, T
      cells, NK cells and monocytes. Chemotaxins, bactericidal activity and
      phagocytosis of neutrophils were normal. DISCUSSION: There have been no case
      reports of selective IgM deficiency with concurrent IgG4 deficiency, various
      dermal symptoms and a bronchial polyp, as demonstrated in our patient.

PMID- 18089939
TI  - Food-dependent exercise-induced anaphylaxis induced by low dose aspirin therapy.
AB  - BACKGROUND: Food-dependent exercise-induced anaphylaxis (FDEIA) is a distinct
      form of common food allergy characteristically induced by a combination of
      causative food ingestion and physical exercise. Recent investigations have
      documented that aspirin consumption, in place of exercise, also induces allergic
      symptoms. CASE SUMMARY: A 63-year-old man began low dose aspirin therapy on
      September 2005. Since January 2006, he had repeated episodes of generalized
      urticaria and lost consciousness while he was exercising after eating wheat. He
      was strongly positive for omega-5 gliadin in a cap-system fluorescent enzyme
      immunoassay. Therefore, a diagnosis of wheat-dependent exercise-induced
      anaphylaxis was made. DISCUSSION: Patients with aspirin-provoked FDEIA have been
      reported previously as taking ordinary doses of aspirin for reducing pain,
      inflammation and fever. However, in our patient, low dose aspirin therapy for
      reducing cardiovascular risk possibility induced FDEIA. Growing numbers of
      elderly people take low doses of aspirin for prevention of cerebral or myocardial
      infarction. Therefore, physicians should remember that aspirin consumption, even
      at low doses, is a risk factor for FDEIA.

PMID- 18089941
TI  - Correlations between alder specific IgE and alder-related tree pollen specific
      IgE by RAST method.
AB  - BACKGROUND: Wild birch trees grow in limited areas in Japan and are not a common
      aero-allergen. However, many patients who do not live in the area show positive
      birch pollen Radioallergosorbent Test (RAST). Therefore, being sensitized by
      another tree pollen which is closely related to birch may result in showing a
      specific IgE antibody to birch. Alder is a one of these trees and in the past it
      grew widely in Japan. However, there is no available RAST data as to the
      correlations between alder and alder-related trees. METHODS: We measured the
      alder specific IgE (CAP-RAST, Phadea) in stored sera which was positive in birch
      RAST (228 samples), beech RAST (36 samples), oak RAST (152 samples) and cedar
      RAST (411 samples) and examined correlations between the RAST of alder and other
      trees. RESULTS: The correlation coefficient value of birch was very high (0.971).
      The other coefficient values of beech and oak were high (0.884 in beech and 0.895
      in oak) but were slightly lower than that of the birch. This means that in terms
      of allergenicities, birch pollen is almost the same as alder and beech and oak
      are partly different from the alder. CONCLUSIONS: The Japanese respond to alder
      pollen just same as they do to birch pollen in forming specific IgE antibody. In
      clinical practice, positive alder RAST has the same meaning as positive birch
      RAST.

PMID- 18089940
TI  - Plasma UGRP1 levels associate with promoter G-112A polymorphism and the severity
      of asthma.
AB  - BACKGROUND: Uteroglobin-related protein 1 (UGRP1) is a secretory protein
      expressed in the airways and is speculated to have anti-inflammatory activity. In
      the mouse, its gene expression is down-regulated by interleukin (IL)-5 and -9,
      and up-regulated by IL-10. However, the precise role of UGRP1 in human
      inflammatory airway diseases such as asthma has not been clarified. The
      objectives of this study were to establish an ELISA system to quantify UGRP1
      protein, and to examine whether plasma UGRP1 levels are associated with the G
      112A polymorphism, asthma susceptibility, and its severity. METHODS: 152 asthma
      patients and 103 normal controls were involved in this study. Mice were immunized
      with recombinant UGRP1 and hybridoma cell lines were established. A sandwich
      ELISA system was established by using two monoclonal antibodies recognizing
      different epitopes. Plasma UGRP1 levels were measured with the ELISA system and
      the G-112A allele was detected by using real-time PCR. RESULTS: An ELISA system
      was established that allowed determination of UGRP1 levels within the range of
      9.6-1250 pg/ml. The mean plasma UGRP1 levels for subjects with -112A allele were
      significantly lower than those without it (p = 0.025). Although there was no
      significant difference in the plasma UGRP1 levels between asthma patients and
      controls (p = 0.13), severe asthma patients without oral corticosteroid had
      significantly lower plasma UGRP1 levels compared to mild- or moderate- asthma
      patients and controls (p = 0.004, 0.03 and 0.003, respectively). CONCLUSIONS: The
      ELISA system for quantifying UGRP1 protein was established, and plasma UGRP1
      levels were associated with the G-112A UGRP1 gene promoter polymorphism and the
      severity of asthma.

PMID- 18089942
TI  - Gut microbiota of children living in rural south Thailand and urban Singapore.
AB  - BACKGROUND: An imbalanced prevalence of allergic diseases occurs in the region of
      South East Asia. It has been suggested that a change in lifestyle associated with
      improved hygiene and modernization has altered the composition of human
      gastrointestinal microbiota, and hence susceptibility to allergy. METHODS: This
      cross-sectional study was designed to investigate the differences between fecal
      microbiota in children living in areas with contrasting socioeconomic
      development. Fecal samples from 73 young children (age 3.0 +/- 0.5) from rural
      Thailand and 69 age-matched children from urban Singapore were collected and
      studied using selective culture. Clinical data were also collected using modified
      ISAAC questionnaires, aiming to identify the key differences in the demographic
      as well as clinical features between the two study groups. RESULTS: The two
      contrasting populations studied differed significantly in multiple lifestyle
      factors such as family size, antibiotic use and sources of drinking water in the
      households. Rural children harbored significantly higher counts of lactic acid
      bacteria (LAB) [7.1 (6.4, 8.3) vs 6.0 (5.3, 7.0) logCFU/g, p < 0.001)], coliforms
      [8.9 (7.3, 10.2) vs 6.9 (5.7, 7.7) logCFU/g, p < 0.001)] as well as staphylococci
      [5.3 (4.8, 6.3) vs 4.3 (3.6, 5.0) logCFU/g, p < 0.001)] than their urban
      counterparts. However, enterococcal counts did not differ between the two groups.
      No single lifestyle factor could be identified to have caused such differences.
      CONCLUSIONS: Certain fecal microbial counts were higher in rural children
      compared with urban children in South East Asia. Several contrasting home
      environmental conditions and practices were also identified. These may serve as a
      basis for future investigation of lifestyle factors underlying the global
      gradient of the increasing trends of allergic diseases.

PMID- 18089944
TI  - All metabolic roads lead to mitochondrial (dys)-function.

PMID- 18089945
TI  - Mitochondrial thermogenesis and obesity.
AB  - PURPOSE OF REVIEW: Thermogenesis is activated at the expense of carbon molecules.
      Mitochondria play a dominant role in oxidation and parallel heat production since
      the recovery of oxidation energy is less than perfect. Recent data of
      mitochondriogenesis and mitochondrial thermogenesis may boost research into
      certain aspects of obesity. RECENT FINDINGS: Recent studies have outlined the
      unexpected decreased thermogenesis that limits fat loss during prolonged food
      restriction. Activation of fat oxidation in skeletal muscle remains a strategy
      against fat accumulation, however. Certain adipose depots have the potential to
      promote thermogenesis, either using mitochondrial uncoupling protein or
      independently. Peroxisome proliferator-activated receptor gamma coactivators
      alpha and ss are important regulators of mitochondria thermogenesis. Brain
      mitochondria are involved in the control of refeeding after starvation. This dual
      action of mitochondria inform their role in thermogenesis and energy
      partitioning. The importance of thyroid hormones in mitochondria thermogenesis is
      also confirmed. SUMMARY: The clinical and research implications of these findings
      are that the mechanisms inhibiting adaptive thermogenesis during diet restriction
      should be investigated. An important field of research is the contribution of
      transcriptional coactivators to adipocyte plasticity since adipocytes have an
      underestimated ability to oxidise fatty acids in addition to their role in
      triglyceride storage.

PMID- 18089946
TI  - Mitochondrial uncoupling as a target in the treatment of obesity.
AB  - PURPOSE OF REVIEW: Obesity is associated with many health problems and its
      prevalence is rapidly increasing worldwide. Very few pharmaceutical compounds are
      available for obesity treatment. Strategies for the development of compounds can
      be targeted to the outcomes of reduced dietary energy intake and/or increased
      energy expenditure/thermogenesis. In this review, we focus on recent discoveries
      that advance our understanding of mitochondrial uncoupling as a target for the
      treatment of obesity. There are various mechanisms whereby uncoupling can occur
      and for the purpose of this review, we elaborate upon the uncoupling that can
      occur (1) through the original uncoupling protein, UCP1, in brown adipocytes, or
      in 'converted' white adipose tissue, and (2) in skeletal muscle. RECENT FINDINGS:
      Studies have identified a number of novel receptors and regulatory proteins
      involved in the emergence of brown adipocytes in white adipose tissue. Molecular
      and pharmacologic approaches in knockout and transgenic mice have demonstrated
      their relevance to obesity treatment. Recent research into uncoupling mechanisms
      in skeletal muscle indicates that uncoupling can occur through basal and
      inducible processes. SUMMARY: Uncoupling is a naturally occurring phenomenon
      whose underlying mechanisms require substantial further study for the development
      of antiobesity therapies.

PMID- 18089947
TI  - Diet, energy metabolism and mitochondrial biogenesis.
AB  - PURPOSE OF REVIEW: This review highlights some recent findings regarding
      nutritional and endocrine regulators of mitochondrial mass and function and their
      association with insulin resistance. RECENT FINDINGS: Insulin resistance is
      central to many chronic metabolic diseases, including obesity, type 2 diabetes,
      dyslipidemia, and hypertension. Insulin resistance in skeletal muscle is
      associated with lower mitochondrial mass and reduced oxidative phosphorylation.
      Part of the mitochondrial dysfunction can be triggered by adverse nutrition.
      Increased fatty acid exposure, resulting from high fats diets or overfeeding, is
      linked to both decreased mitochondrial number and markers of oxidative
      phosphorylation. Caloric restriction and the adiponectin signaling pathway,
      however, can stimulate mitochondrial biogenesis by elevating the transcriptional
      machinery that regulates mitochondrial mass, improving mitochondrial efficiency,
      activating the peroxisome proliferator-activated receptor coactivator 1alpha
      mediated reactive oxygen species scavenging mechanism, and lowering reactive
      oxygen species production. SUMMARY: States of insulin resistance are
      characterized by defects in lipid and carbohydrate metabolism. Abnormalities in
      oxidative capacity, however, can be partially normalized by caloric restriction
      by modulating mitochondrial mass in an insulin sensitizing manner.

PMID- 18089948
TI  - Mitochondrial dysfunction and age.
AB  - PURPOSE OF REVIEW: Mitochondrial dysfunction is commonly thought to result from
      oxidative damage that leads to defects in the electron transport chain (ETC). In
      this review, we highlight new research indicating that there are early changes in
      mitochondrial function that precede ETC defects and are reversible thereby
      providing the possibility of slowing the tempo of mitochondrial aging and cell
      death. RECENT FINDINGS: Increased mitochondrial uncoupling - reduced adenosine
      triphosphate (ATP) produced per O2 uptake - and cell ATP depletion are evident in
      human muscle nearly a decade before accumulation of irreversible DNA damage that
      causes ETC defects. New evidence points to reduction in activators of biogenesis
      (e.g. PGC-1alpha) and to degradation of mitochondria allowing accumulation of
      molecular and membrane damage in aged mitochondria. The early dysfunction appears
      to be reversible based on improved mitochondrial function in vivo and elevated
      gene expression levels after exercise training. SUMMARY: New molecular and in
      vivo findings regarding the onset and reversibility of mitochondrial dysfunction
      with age indicate the potential: 1) for diagnostic tools to identify patients at
      risk for severe irreversible defects later in life; and 2) of an intervention to
      delay the tempo of aging and improve the quality of life of the elderly.

PMID- 18089949
TI  - Lessons that can be learned from patients with diabetogenic mutations in
      mitochondrial DNA: implications for common type 2 diabetes.
AB  - PURPOSE OF REVIEW: To discuss the role of mitochondria in the development of type
      2 diabetes. RECENT FINDINGS: Some mutations in mitochondrial DNA are diabetogenic
      due to a gradual decline in insulin secretion by the pancreas. These mutations
      also result in abnormalities in lipid metabolism. A similar situation is seen in
      patients treated with nucleoside analogues as part of highly active
      antiretroviral therapy to suppress human immunodeficiency virus infection. These
      drugs induce a 30-50% reduction in mitochondrial DNA copy number in multiple
      tissues. Treated individuals develop a redistribution of body fat with
      concomitant development of markers of the metabolic syndrome and an elevated risk
      of developing type 2 diabetes. Studies have also shown the presence of reduced
      mitochondrial activity in muscle and adipose tissue in individuals with type 2
      diabetes. SUMMARY: These observations suggest a pathogenic model for obesity
      associated type 2 diabetes, in which mitochondrial activity in peripheral
      adipocytes is essential to keep triacylglycerol stored within these cells.
      Mitochondria protect the organism against fatty acid-induced insulin resistance
      and lipotoxicity to the pancreas. In adipocytes, mitochondria may remove fatty
      acids through uncoupled beta oxidation, whereas in muscle fatty acids, removal is
      largely driven by adenosine diphosphate production through physical activity.

PMID- 18089950
TI  - Muscular mitochondrial dysfunction and type 2 diabetes mellitus.
AB  - PURPOSE OF REVIEW: Muscular mitochondrial dysfunction, leading to the
      accumulation of fat in skeletal muscle, has been proposed to be involved in the
      development of type 2 diabetes mellitus. Here, we review human studies that
      investigated various aspects of mitochondrial function in relation to muscular
      insulin sensitivity and/or diabetes. RECENT FINDINGS: In-vivo magnetic resonance
      spectroscopy allows assessment of mitochondrial functionality from adenosine
      triphosphate flux in the nonexercising state and from phosphocreatine recovery
      from (sub)maximal exercising. Application of both approaches revealed reduced
      mitochondrial oxidative capacity in insulin-resistant (pre)diabetic humans.
      Reductions in mitochondrial density may contribute to, or even underlie, these
      findings as well as intrinsic defects in mitochondrial respiration. So far, only
      two studies reported measurements of mitochondrial respiratory capacity in intact
      mitochondria in diabetic patients, with inconsistent findings. SUMMARY: Muscular
      mitochondrial aberrations in type 2 diabetes mellitus can be detected, but it is
      so far unclear if these aberrations are causally related to the development of
      the disease. Alternatively, mitochondrial dysfunction may simply be the
      consequence of elevated plasma fatty acids or glucose levels.

PMID- 18089951
TI  - Mitochondria and heart failure.
AB  - PURPOSE OF REVIEW: Energetic abnormalities in cardiac and skeletal muscle occur
      in heart failure and correlate with clinical symptoms and mortality. It is likely
      that the cellular mechanism leading to energetic failure involves mitochondrial
      dysfunction. Therefore, it is crucial to elucidate the causes of mitochondrial
      myopathy, in order to improve cardiac and skeletal muscle function, and hence
      quality of life, in heart failure patients. RECENT FINDINGS: Recent studies
      identified several potential stresses that lead to mitochondrial dysfunction in
      heart failure. Chronically elevated plasma free fatty acid levels in heart
      failure are associated with decreased metabolic efficiency and cellular insulin
      resistance. Tissue hypoxia, resulting from low cardiac output and endothelial
      impairment, can lead to oxidative stress and mitochondrial DNA damage, which in
      turn causes dysfunction and loss of mitochondrial mass. Therapies aimed at
      protecting mitochondrial function have shown promise in patients and animal
      models with heart failure. SUMMARY: Despite current therapies, which provide
      substantial benefit to patients, heart failure remains a relentlessly progressive
      disease, and new approaches to treatment are necessary. Novel pharmacological
      agents are needed that optimize substrate metabolism and maintain mitochondrial
      integrity, improve oxidative capacity in heart and skeletal muscle, and alleviate
      many of the clinical symptoms associated with heart failure.

PMID- 18089952
TI  - Markers of oxidative stress in ICU clinical settings: present and future.
AB  - PURPOSE OF REVIEW: Oxidative stress is associated with most conditions requiring
      intensive care: it contributes to clinical complications, organ failure and
      mortality. Interestingly, no unique definition exists of oxidative stress, of how
      it contributes to the clinical worsening and most importantly, no common strategy
      exists about its measurement. Despite these metrology problems, limiting the
      intensity of oxidative stress has become a popular therapeutic target. The paper
      reviews methods used to determine oxidative stress in clinical situations using
      routine validated methods or those used by research laboratories. RECENT
      FINDINGS: Many methods of measuring oxidative stress have proven unreliable and
      no single method exists enabling objective determination and characterization of
      oxidative stress in clinical settings whether in critical illness or in chronic
      disease. Some methods, like determination of malondialdehyde, F2-isoprostanes, or
      8-hydroxydesoxyguanosine, are widely used to determine oxidative stress. Other
      methods - such as the determination of vitamins or micronutrients - are able to
      determine components of the antioxidant defense. No single method, however, is
      yet alone able to characterize oxidative stress under clinical conditions.
      SUMMARY: Today, strategies to measure oxidative stress are limited in clinical
      settings. The most reliable available marker remains malondialdehyde or F2
      isoprostanes, in combination with circulating levels of micronutrients.

PMID- 18089953
TI  - Homocysteine as a biomarker for cognitive dysfunction in the elderly.
AB  - PURPOSE OF REVIEW: Homocysteine and B vitamins have been investigated in
      association with cognitive dysfunction in healthy and in multimorbid elderly
      patients. Whether reduction of hyperhomocystemia is reducing the risk of dementia
      or Alzheimer's disease is still under investigation. RECENT FINDINGS: High
      homocysteine concentrations are associated with poorer cognitive function but can
      be influenced by a number of factors. The results of epidemiological studies are
      inconsistent in showing an association between elevated homocysteine levels and
      dementia or Alzheimer disease. Although prospective studies show a trend towards
      a benefit of homocysteine-related B vitamin substitution, consistent data are
      expected from upcoming clinical intervention trials. Data from recent clinical
      randomized trials including various cognitive tests, different aging groups and
      supplements in different doses are not sufficient to allow recommendation of
      homocysteine-reducing therapy with folate or vitamin B12 substitution. According
      to the published data it remains to be proven whether a reduction in homocysteine
      will improve cognitive performance. SUMMARY: Homocysteine by itself is not a
      useful marker for screening cognitive decline, or Alzheimer disease but works as
      a surrogate parameter for malnutrition and organ insufficiency in the cognitive
      declining patient.

PMID- 18089955
TI  - Gut microflora as a target for energy and metabolic homeostasis.
AB  - PURPOSE OF REVIEW: Gut microbiota plays an important role in health and disease,
      but this ecosystem remains incompletely characterized and shows a wide diversity.
      This review discusses new findings that may explain how gut microbiota can be
      involved in the control of energy and metabolic homeostasis. RECENT FINDINGS:
      Over the past 5 years studies have highlighted some key aspects of the mammalian
      host-gut microbial relationship. Gut microbiota could now be considered a
      'microbial organ' placed within a host organ. Recent data suggest that the
      modulation of gut microbiota affects host metabolism and has an impact on energy
      storage. Several mechanisms are proposed that link events occurring in the colon
      and the regulation of energy metabolism. SUMMARY: Gut microflora may play an even
      more important role in maintaining human health than previously thought. The
      literature provides new evidence that the increased prevalence of obesity and
      type 2 diabetes cannot be attributed solely to changes in the human genome,
      nutritional habits, or reduction of physical activity in our daily lives. One
      must also consider this important new environmental factor, namely gut
      microbiota. Scientists may take into consideration a key question: could we
      manipulate the microbiotic environment to treat or prevent obesity and type 2
      diabetes? This opens up a new area in nutrition research.

PMID- 18089954
TI  - Polyphenols and inflammation: basic interactions.
AB  - PURPOSE OF REVIEW: For more than 20 years polyphenols, food-derived bioactive
      compounds in fruits and vegetables, are claimed to help prevent cancer,
      degenerative diseases and chronic and acute inflammation. Modern methods in cell
      and molecular biology allow us to understand the interactions of different
      polyphenols with basic mechanisms of inflammatory response. This review
      summarizes recent papers dealing with the effect of polyphenols on modulators of
      the inflammatory cascade. RECENT FINDINGS: The majority of papers deal with the
      effects of different antioxidants on the redox sensitive transcription factor
      nuclear factor kappaB, inducible nitric oxide synthase expression and
      cyclooxygenase inhibition. Understanding the regulatory steps and the multiple
      potential actions of polyphenols within the inflammatory cascade may help to
      define special polyphenols to be used for prevention and intervention in clinical
      conditions of inflammation. The relation between formation of advanced glycation
      end products as a consequence of high glucose and the activation of defence
      mechanisms through polyphenols opens new fields in the prevention and treatment
      of oxidative stress and hyperglycemia. SUMMARY: Polyphenols are promising
      compounds that may help to control oxidative stress and consequently inflammatory
      response. To date, however, clinical studies are missing and should be carried
      out with specific polyphenols.

PMID- 18089956
TI  - Endocannabinoids and related N-acylethanolamines in the control of appetite and
      energy metabolism: emergence of new molecular players.
AB  - PURPOSE OF REVIEW: Endocannabinoids (anandamide and 2-arachidonoylgycerol) and
      related N-acylethanolamines (N-oleoylethanolamine) exhibit opposite effects in
      the control of appetite. The purpose of this review is to highlight the
      similarities and differences of three major lipid-signaling molecules by focusing
      on their mode of action and the proteins involved in the control of food intake
      and energy metabolism. RECENT FINDINGS: Anandamide and 2-arachidonoylglycerol
      promote food intake and are the main endogenous ligands of the cannabinoid
      receptors. One of them, the cannabinoid receptor 1, is responsible for the
      control of food intake and energy expenditure both at a central and a peripheral
      level, affecting numerous anorexigenic and orexigenic mediators (leptin,
      neuropeptide Y, ghrelin, orexin, endogenous opioids, corticotropin-releasing
      hormone, alpha-melanocyte stimulating hormone, cocaine and amphetamine-related
      transcript). In the gut, N-oleoylethanolamine plays an opposite role in food
      regulation, by interacting with two molecular targets different from the
      cannabinoid receptors: the nuclear receptor peroxisome proliferator-activated
      receptor alpha and a G-protein coupled receptor GPR119. SUMMARY: Recent findings
      on the molecular mechanisms underlying the promotion of food intake or, in
      contrast, the suppression of food intake by anandamide and N-oleoylethanolamine,
      are summarized. Potential strategies for treating overweight, metabolic syndrome,
      and type II diabetes are briefly outlined.

PMID- 18089957
TI  - Coffee, caffeine, and coronary heart disease.
AB  - PURPOSE OF REVIEW: This review summarizes and highlights recent advances in
      current knowledge of the relationship between coffee and caffeine consumption and
      risk of coronary heart disease. Potential mechanisms and genetic modifiers of
      this relationship are also discussed. RECENT FINDINGS: Studies examining the
      association between coffee consumption and coronary heart disease have been
      inconclusive. Coffee is a complex mixture of compounds that may have either
      beneficial or harmful effects on the cardiovascular system. Randomized controlled
      trials have confirmed the cholesterol-raising effect of diterpenes present in
      boiled coffee, which may contribute to the risk of coronary heart disease
      associated with unfiltered coffee consumption. A recent study examining the
      relationship between coffee and risk of myocardial infarction incorporated a
      genetic polymorphism associated with a slower rate of caffeine metabolism and
      provides strong evidence that caffeine also affects risk of coronary heart
      disease. Several studies have reported a protective effect of moderate coffee
      consumption, which suggests that coffee contains other compounds that may be
      beneficial. SUMMARY: Diterpenes present in unfiltered coffee and caffeine each
      appear to increase risk of coronary heart disease. A lower risk of coronary heart
      disease among moderate coffee drinkers might be due to antioxidants found in
      coffee.

PMID- 18089959
TI  - Bibliography. Current world literature. Nutrition and physiological function.

PMID- 18089958
TI  - Saturated fatty acids: simple molecular structures with complex cellular
      functions.
AB  - PURPOSE OF REVIEW: This review summarizes recent findings on the biological
      functions of saturated fatty acids. Some of these findings suggest that saturated
      fatty acids may have important and specific regulatory roles in the cells. Until
      now these roles have largely been outweighed by the negative impact of dietary
      saturated fatty acids on atherosclerosis biomarkers. Elucidated biochemical
      mechanisms like protein acylation (N-myristoylation, S-palmitoylation) and
      putative physiological roles are described. RECENT FINDINGS: The review will
      focus on the following topics: new aspects on the metabolism of saturated fatty
      acids; recent reports on the biochemical functions of saturated fatty acids;
      current investigations on the physiological roles (elucidated and putative) of
      saturated fatty acids; and a discussion of the nutritional dietary
      recommendations (amounts and types) of saturated fatty acids. SUMMARY: Dietary
      saturated fatty acids are usually associated with negative consequences for human
      health. Experimental results on the relationship between doses, physiological
      effects, specificities and functions of individual saturated fatty acids are,
      however, conflicting. In this context, this review describes emerging recent
      evidence that some saturated fatty acids have important and specific biological
      roles. Such data are needed to allow a balanced view in terms of potential
      nutritional benefits of saturated fatty acids, and, if necessary, reassessment of
      the current nutritional dietary recommendations.

PMID- 18089961
TI  - The doctor-patient relationship in living donor kidney transplantation.
AB  - PURPOSE OF REVIEW: A therapeutic and effective doctor-patient relationship and
      patient-doctor relationship is at the core of all successful medical care. The
      medical and psychological evaluation of a potential kidney donor serves to
      protect the long-term health of both the donor and the potential recipient.
      Careful assessment of risk and donor education is at the core of donor evaluation
      and the decision to progress with donation requires refined clinical judgment by
      the medical team and critical thinking by the donor. RECENT FINDINGS: Increasing
      pressure to increase the numbers of living donor transplants and suggestions by
      some that the process should be commercialized make it timely to consider the
      nature of the relationship between the doctor and the patient in the unusual
      circumstance of living donation. A high rate of complications in recipients of
      purchased kidneys and a lack of knowledge of the fate of paid donors have been
      reported. SUMMARY: Commercialization of transplantation undermines the
      therapeutic doctor-patient relationship and threatens the healthy development of
      the international transplant endeavor.

PMID- 18089962
TI  - Are biomarkers useful for assessing cardiovascular risk in patients with chronic
      kidney disease?
AB  - PURPOSE OF REVIEW: Chronic kidney disease is now recognized as an independent
      risk factor for cardiovascular events, and cardiovascular disease is the major
      cause of mortality in patients with the disease. Recent studies have attempted to
      evaluate the utility of biomarkers for assessing cardiovascular risk in patients
      with chronic kidney disease. This review will summarize these studies and
      critically assess the utility of cardiovascular risk biomarkers for clinical
      practice. RECENT FINDINGS: Traditional cardiovascular risk factors including
      dyslipidemia, hypertension, smoking and diabetes mellitus are highly prevalent in
      patients with chronic kidney disease. Although prediction models using
      traditional risk factors underestimate cardiovascular disease risk in these
      patients, nontraditional biomarkers (i.e. markers of inflammation, endothelial
      dysfunction, myocardial necrosis, and left ventricular remodeling) have been
      associated with increased cardiovascular event rates and mortality risk in
      populations with and without chronic kidney disease. Moreover, a high prevalence
      of biomarkers that are directly attributable to loss of kidney function is
      observed in patients with the disease. SUMMARY: Recent studies suggest only
      limited utility of either single or multiple biomarkers of cardiovascular risk as
      prognostic tools in patients with and without chronic kidney disease. Novel
      approaches for biomarker development capturing augmented information through a
      systems biology approach are urgently needed to improve the usefulness of
      cardiovascular risk biomarkers.

PMID- 18089963
TI  - The development of new allocation policy for deceased donor kidneys.
AB  - PURPOSE OF REVIEW: The current system of kidney allocation in the United States
      has been undergoing review by the Organ Procurement and Transplantation Network.
      The Organ Procurement and Transplantation Network kidney committee is nearing the
      release of a draft proposal for sweeping changes in kidney allocation. The
      involvement of the renal community is critical to the successful development and
      implementation of these new policies. RECENT FINDINGS: This review describes
      ethical issues related to allocation of scarce resources such as kidneys, the
      current US kidney allocation system and problems associated with it, as well as
      the development of a new model for kidney allocation. The new paradigm involves
      the application of 'life years from transplant'--an approach that compares
      predicted survival of a recipient after transplant versus remaining on dialysis,
      adjusted for multiple factors such as cause of renal failure, age and co-morbid
      conditions. Alternate systems as well as criticism of the current proposals are
      presented. SUMMARY: The use of life years from transplant would increase
      allocation of kidneys to patients more likely to benefit from transplantation,
      resulting in many thousands of additional life-years saved. Such a scheme would
      also tend to assign these kidneys to younger patients, which has generated
      controversy.

PMID- 18089964
TI  - Vascular stenosis: biology and interventions.
AB  - PURPOSE OF REVIEW: The aim of this review will be to summarize recent concepts
      pertaining to the pathophysiology of dialysis access stenosis and to then use
      this information to highlight novel interventions (both diagnostic and
      therapeutic) for dialysis access dysfunction. The studies covered in this review
      will include experimental and observational studies in addition to clinical
      trials. RECENT FINDINGS: An important biological focus of this review will be an
      emphasis on the role of the adventitia and progenitor cells in the pathogenesis
      of dialysis access dysfunction. The main interventional focus will be on access
      surveillance, local drug delivery and other novel therapeutic interventions. An
      important underlying theme throughout this review will be an emphasis on
      arteriovenous fistulae and on the many advantages of local therapeutic
      interventions in the specific clinical setting of dialysis access dysfunction.
      SUMMARY: Vascular access dysfunction remains a significant cause of morbidity and
      mortality for hemodialysis patients. We believe that a better understanding of
      the biological mechanisms of vascular access stenosis will help guide the
      development of novel therapies to prevent and treat dialysis access stenosis.

PMID- 18089965
TI  - Cancer after renal transplantation.
AB  - PURPOSE OF REVIEW: Prolonged waiting times for renal transplantation, an increase
      in the average age of recipients, decreased acute rejection rates due to use of
      newer potent immunosuppressives and improving long-term transplant survival have
      raised concerns in the transplant community regarding posttransplant cancer. In
      view of the fact that transplant recipients are living longer, it is of paramount
      importance that we continue to translate discoveries at the bench to the bedside
      and document cancers in the posttransplant recipient registries. Analysis of data
      will help in optimizing patient management. RECENT FINDINGS: Recent evidence
      indicates that sirolimus is associated with a decreased incidence of
      posttransplant de-novo cancer and remission of Kaposi's sarcoma and nonmelanoma
      skin cancer. Mycophenolate mofetil has been shown to have an antiproliferative
      activity against leukemia and lymphoma and an anti-tumor effect against colon and
      prostate cancer. Clinically it has been shown to be associated with a reduced
      incidence of cancers like posttransplant lymphoproliferative disorder. SUMMARY:
      Appropriate selection of transplant candidates, pretransplant and posttransplant
      cancer surveillance and judicious evidence-based use of newer immunosuppressants
      may help reduce the incidence and improve the outcome of posttransplant cancer.

PMID- 18089966
TI  - ABO incompatible kidney transplantation.
AB  - PURPOSE OF REVIEW: Although ABO incompatible kidney transplantation is
      increasingly recognized as effective, the procedure is still evolving. The
      purpose of this review is to summarize recent advances in this area. RECENT
      FINDINGS: Short to intermediate-term outcome appears good, although long-term
      results are still preliminary. Pretransplant risk stratification based on
      antidonor antibody titer may be of limited value. Splenectomy, previously
      reported to be an important component of ABO incompatible transplantation,
      appears to be avoidable under many circumstances. The wider implementation of A2
      blood group incompatible transplantation shortens waiting time for deceased donor
      transplantation of blood group B recipients without significantly disadvantaging
      others. The diagnosis of acute humoral rejection has become clearer following the
      recognition that C4d deposition commonly occurs in well functioning ABO
      incompatible allografts. The long-term implications of acute humoral rejection
      appear substantial even following successful acute therapy, with a significant
      percentage of patients developing chronic humoral rejection manifested as
      transplant glomerulopathy. Finally, although ABO incompatible transplantation
      entails increased expense, when compared with maintenance dialysis and taking
      into account the health related quality of life benefits of a successful
      transplant, it is clearly cost effective. SUMMARY: ABO incompatible kidney
      transplantation is an effective therapy, and will become more widely implemented
      in the future.

PMID- 18089967
TI  - Minimization of immunosuppression in kidney transplantation.
AB  - PURPOSE OF REVIEW: In an effort to reduce the long-term toxicities of
      immunosuppressant drugs, corticosteroid and calcineurin inhibitor-sparing
      immunosuppression protocols have become increasingly popular in managing kidney
      transplant recipients. This article focuses on outcomes of these strategies
      described in recently published trials. RECENT FINDINGS: The use of induction
      antibody therapy and potent residual immunosuppressants has increased the safety
      of steroid-free regimens, resulting in a paradigm shift towards earlier
      elimination of steroids after kidney transplantation. Even in the modern era,
      results of randomized trials generally indicate that steroid elimination
      increases the risk of rejection compared with maintenance steroid therapy. Among
      calcineurin inhibitor-sparing strategies, withdrawal of these agents after their
      initial use in stable patients, or conversion to either mycophenolate mofetil or
      sirolimus in patients with early renal dysfunction appears to yield the greatest
      benefit in preserving renal function. The outcomes of calcineurin inhibitor
      avoidance protocols have been mixed and have fallen into disfavor. SUMMARY: The
      benefits of minimizing immunosuppression in kidney transplant recipients must be
      weighed against the risks of precipitating acute rejection or chronic allograft
      dysfunction. Additional research is needed to identify clinical and immune
      parameters that will enable selection of patients for whom the benefits outweigh
      the risks.

PMID- 18089968
TI  - Therapeutic strategy for cachexia in chronic kidney disease.
AB  - PURPOSE OF REVIEW: This review will provide an update on advances in the
      understanding of the pathophysiology and novel therapeutic approach to cachexia
      in chronic kidney disease. RECENT FINDINGS: Recent studies examine the metabolic
      effects of nutritional supplementation and show short-term salutary effects.
      Studies on peripheral hormones involved in energy homeostasis and their
      hypothalamic signaling in the pathophysiology of uremic cachexia have led to
      potential novel therapeutic strategies. SUMMARY: Most of the information on
      therapeutic strategy for cachexia of chronic kidney disease is currently at the
      experimental level and awaits confirmation by clinical trials. The few available
      clinical studies are preliminary and have the limitation of not having a
      randomized placebo-controlled group. Further long-term well designed studies to
      assess the clinical applicability as well as side-effects are needed before these
      therapeutic strategies can be recommended for treatment of cachexia in chronic
      kidney disease.

PMID- 18089969
TI  - Simultaneous liver and kidney transplantation.
AB  - PURPOSE OF REVIEW: The Model for End-Stage Liver Disease (MELD) scoring system
      for prioritizing patients for liver transplantation heavily weights serum
      creatinine, leading to increased numbers of liver transplant patients with renal
      insufficiency receiving both liver-alone transplants and liver-kidney
      transplants. With available organs being scarce, review of recent outcomes and
      guidelines for their use is timely. RECENT FINDINGS: Despite lower average renal
      function in liver transplant recipients in the era of Model for End-Stage Liver
      Disease scoring, and poor renal function predicting inferior outcomes, overall
      outcomes are unchanged. Combined liver-kidney transplants have increased three
      fold. Despite inferior short-term kidney and liver-graft survival rates, long
      term success rates are equivalent to single-organ transplantation. Only patients
      requiring dialysis at the time of transplantation clearly benefit from combined
      liver-kidney transplants. Waitlisted patients with nonresolving severe acute
      kidney injury for 6-8 weeks or substantial irreversible renal parenchymal damage
      are also deemed appropriate candidates. Many combined liver-kidney recipients
      have lesser degrees of renal dysfunction, however. Accurate determination of
      renal function in patients with cirrhosis remains problematic. SUMMARY:
      Appropriate patients with irreversible end-stage renal and liver disease clearly
      deserve combined liver-kidney transplants. More data on the reliable assessment
      of renal function, renal pathology, and outcomes are needed, however.

PMID- 18089970
TI  - Defining renal risk.

PMID- 18089971
TI  - Biomarkers for the diagnosis of acute kidney injury.
AB  - PURPOSE OF REVIEW: The identification of acute kidney injury relies on tests like
      blood urea nitrogen and serum creatinine that were identified and incorporated
      into clinical practice several decades ago. This review summarizes clinical
      studies of newer biomarkers that may permit earlier and more accurate
      identification of acute kidney injury. RECENT FINDINGS: The urine may contain
      sensitive and specific markers of kidney injury that are present due to either
      impaired tubular reabsorption and catabolism of filtered molecules or release of
      tubular cell proteins in response to ischemic or nephrotoxic injury. Many
      potential markers have been studied. Promising injury markers in the urine
      include N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated
      lipocalin, kidney injury molecule-1, and interleukin-18. Serum cystatin C may be
      a better measure of glomerular filtration rate than serum creatinine or blood
      urea nitrogen. SUMMARY: New biomarkers of kidney injury and glomerular filtration
      rate hold the promise of substantially improving the diagnostic approach to acute
      kidney injury. Adequately powered clinical studies of multiple biomarkers are
      needed to qualify the biomarkers before they can be fully adopted in clinical
      practice. Once adopted, more sensitive biomarkers of acute kidney injury hold the
      potential to transform the care of patients with renal disease.

PMID- 18089972
TI  - Update on evaluating complement in hemolytic uremic syndrome.
AB  - PURPOSE OF REVIEW: The last few years have seen the decoding of the genetic basis
      for atypical hemolytic uremic syndrome. RECENT FINDINGS: Mutations in complement
      factor H were the first to be associated with atypical hemolytic uremic syndrome.
      These mutations cluster in the C-terminus of complement factor H. This year has
      seen the publication of a transgenic mouse model lacking the C-terminus of
      complement factor H, which spontaneously develops atypical hemolytic uremic
      syndrome. This mouse model regulated C3 activation in plasma but failed to bind
      to endothelial cells in an analogous manner to the mutations seen in atypical
      hemolytic uremic syndrome patients. This year has also seen the emergence of
      genotype-phenotype correlations in atypical hemolytic uremic syndrome. Patients
      with membrane cofactor protein mutations have a good prognosis and in those who
      do develop endstage renal disease, recurrence after transplantation is rare. By
      contrast, the outcome for patients with complement factor H and complement factor
      I mutations is poor and the rate of recurrence after transplantation is high. New
      complement genes associated with atypical hemolytic uremic syndrome have also
      been described in the past year including factor B, C3, C4b-binding protein, FHR1
      and FHR3. SUMMARY: Genetic screening is now providing prognostically significant
      information in predicting survival, renal recovery and transplant outcome. It
      paves the way for the use of complement inhibitors in the future.

PMID- 18089974
TI  - Evaluation of blood pressure in children.
AB  - PURPOSE OF REVIEW: This review briefly highlights origins of hypertension with
      emphasis on the influences of gestation, birth weight, salt intake, and
      adiposity. We focus on the role of ambulatory blood pressure monitoring, and the
      assessment of comorbidity and target organ change in hypertensive children and
      adolescents. RECENT FINDINGS: Low birth weight, prematurity and uric acid levels
      are associated with hypertension early in childhood and in young adult life, not
      just in later adult life. Reduction of dietary salt intake leads to significant
      reductions in blood pressure in infants and young children. Newly applied
      techniques for assessment of target organ damage in children include arterial
      studies using retinal photography, ultrasound assessment of arterial intima-media
      thickness, and applanation tonometry. SUMMARY: Overweight and obesity are
      increasingly common, and are major determinants of high blood pressure in
      children, in both the developed and developing world. Initial evaluation of the
      hypertensive child must include carefully confirming if they are hypertensive
      using published reference data for blood pressure in children, and increasingly
      through ambulatory blood pressure monitoring. Left ventricular hypertrophy based
      on echocardiography remains the most widely used indirect marker of hypertensive
      end organ change. New techniques for assessing target organ damage are being
      developed.

PMID- 18089973
TI  - Body fat measurement in chronic kidney disease: implications in research and
      clinical practice.
AB  - PURPOSE OF REVIEW: The paradoxical and inverse association between body mass
      index and mortality risk in patients with end-stage renal disease has raised a
      question of whether an increased fat mass is good or bad for patients with
      chronic kidney disease. The purpose of this review is to update the concept on
      body fat in patients with chronic kidney disease. RECENT FINDINGS: A greater fat
      mass is an independent predictor of better survival in patients on maintenance
      hemodialysis. Following the initiation of dialysis, chronic kidney disease
      patients gain body weight due mainly to increased fat mass. Fat mass gain over
      time predicts better survival in hemodialysis patients. In predialysis chronic
      kidney disease, there is also an inverse association between body mass index and
      mortality risk. The metabolic syndrome and a high body mass index are independent
      predictors for development of chronic kidney disease and end-stage renal disease,
      respectively. In diabetic patients with chronic kidney disease, however, a high
      initial body mass index is associated with a slower decline in glomerular
      filtration rate. SUMMARY: The impacts of fat mass on survival and renal function
      appear to vary depending upon the absence or presence, and stages of chronic
      kidney disease. Further research is required for optimal nutritional management
      and improved outcomes of patients with chronic kidney disease.

PMID- 18089975
TI  - Epoetin-induced pure red cell aplasia: diagnosis and treatment.
AB  - PURPOSE OF REVIEW: Antibody-mediated pure red cell aplasia is now recognized as a
      rare complication of erythropoiesis-stimulating agent therapy. The incidence of
      this adverse effect peaked in 2002, but new cases still appear sporadically. The
      aim of this review is to discuss the latest opinions regarding the detection and
      management of this condition. RECENT FINDINGS: The diagnosis of classical
      erythropoiesis-stimulating agent induced pure red cell aplasia is made by a
      constellation of clinical features, including severe transfusion-dependent
      anaemia, reticulocytopenia, low or absent erythroblasts in the bone marrow, and
      the presence of circulating antierythropoietin antibodies. Recently, some cases
      have been reported in which the bone marrow findings show red cell hypoplasia
      rather than aplasia; this may represent earlier presentations of the same
      condition. SUMMARY: Management of pure red cell aplasia as a complication of
      erythropoiesis-stimulating agent therapy consists of stopping the drug and
      implementing an immunosuppressive regimen to reduce or abolish erythropoietin
      antibody production. A recent animal study suggested that a possible alternative
      strategy may be to administer a novel peptide-based erythropoietin receptor
      agonist called Hematide that does not cross react with antierythropoietin
      antibodies, and will allow ongoing stimulation of erythropoiesis; this is the
      subject of a current clinical trial.

PMID- 18089976
TI  - Albumin dialysis: an update.
AB  - PURPOSE OF REVIEW: To review the current literature about albumin dialysis-based
      liver support. RECENT FINDINGS: The literature suggests that the molecular
      adsorbent recirculating system of albumin dialysis is a useful tool to treat
      acute liver failure, decompensated chronic liver disease, and to provide a bridge
      for patients to liver transplantation. The reported clinical benefits include an
      improvement in central and local haemodynamics as well as organ functions (liver,
      brain, kidney). The treatment can contribute to liver regeneration and
      prolongation of patient survival. Proper patient selection is critical for
      clinical success. SUMMARY: Albumin regeneration has developed into a central
      component of modern liver support technologies. Albumin dialysis using the
      molecular adsorbent recirculating system is the most frequently used and best
      studied liver support technique at present time. Ongoing and future clinical
      studies will help define the place of albumin dialysis in liver failure therapy.

PMID- 18089977
TI  - Bibliography. Current world literature. Dialysis and transplantation.

PMID- 18089979
TI  - Intimate partner violence perpetration against main female partners among HIV
      positive male injection drug users.
AB  - Intimate partner violence (IPV) against women is a serious public health and
      social problem and is associated with a host of adverse health outcomes and
      behaviors, HIV risk behaviors included, among women who are victimized.
      Historically, research has focused on correlates of IPV victimization among
      women; thus, there is less information on the role of men in perpetrating IPV,
      particularly among men at risk for transmitting HIV to their female partners. We
      assessed the self-reported prevalence and correlates of perpetration and threat
      of perpetration of physical and/or sexual IPV against a main female partner among
      317 HIV-positive men who were current injection drug users (IDUs). More than 40%
      of men reported perpetrating physical (39%) and/or sexual (4%) violence against
      their main female partners in the past year. Multivariate analyses revealed that
      low education, homelessness, psychologic distress, and unprotected sex with main
      and nonmain HIV-negative female partners were positively associated with IPV
      perpetration against main female partners. These findings reveal that IPV
      perpetration is prevalent among HIV-positive male IDUs and associated with sexual
      HIV transmission risk behaviors. IPV assessment and treatment among HIV-positive
      men in HIV care is recommended as a way to prevent IPV perpetration and
      victimization and to reduce potential HIV transmission.

PMID- 18089980
TI  - Microsocial environmental influences on highly active antiretroviral therapy
      outcomes among active injection drug users: the role of informal caregiving and
      household factors.
AB  - Active injection drug users (IDUs) are at high risk of unsuccessful highly active
      antiretroviral therapy (HAART). We sought to identify baseline factors
      differentiating IDUs' treatment success versus treatment failure over time among
      those taking HAART. Interventions for Seropositive Injectors-Research and
      Evaluation (INSPIRE) study participants were assessed at baseline and at 6- and
      12-month follow-ups. Multinominal regression determined baseline predictors of
      achieving or maintaining viral suppression relative to maintaining detectable
      viral loads over 12 months. Of 199 participants who were retained and remained on
      HAART, 133 (67%) had viral load change patterns included in the analysis. At
      follow-up, 66% maintained detectable viral loads and 15% achieved and 19%
      maintained viral suppression. Results indicated that those having informal care
      (instrumental or emotional support) were 4.6 times more likely to achieve or
      maintain viral suppression relative to experiencing treatment failure. Those who
      maintained viral suppression were 3.5 times less likely to live alone or to
      report social discomfort in taking HAART. Study results underscore the importance
      of microsocial factors of social network support, social isolation, and social
      stigma for successful HAART outcomes among IDUs. The findings suggest that
      adherence interventions for IDUs should promote existing informal HIV caregiving,
      living with supportive others, and positive medication-taking norms among social
      networks.

PMID- 18089981
TI  - Longitudinal correlates of health care-seeking behaviors among HIV-seropositive
      injection drug users: how can we intervene to improve health care utilization?
AB  - OBJECTIVE: To identify modifiable factors associated with health care utilization
      by HIV-negative seropositive injection drug users (IDUs). METHODS: We analyzed
      longitudinal data from 966 participants in a randomized controlled trial of a
      behavioral intervention designed to address medical care, adherence, and risk
      reduction. The outcomes of this study were usual place for care (clinic vs.
      emergency room) and frequency of primary care visits. RESULTS: Results of
      multiple logistic regression analysis showed that increase in "importance of HIV
      care scale" score (odds ratio [OR]=2.99; P<0.001), empowerment (OR=3.53;
      P<0.001), utilization of case management (OR=3.07; P=0.007), and having a stable
      residence (OR=2.63; P=0.008) were significantly associated with participants
      being "clinic users." Increase in importance of HIV care scale score (OR=5.65;
      P=0.01) increased empowerment (OR=2.42; P=0.005), taking greater control of one's
      health (OR=2.17; P=0.001), having health insurance (OR=2.58; P=0.003),
      utilization of case management (OR=3.14; P=0.027), and CD4 count>or=200 cells/mm
      (OR=2.09; P=0.007) were significantly associated with reporting 2 or more primary
      HIV care visits in the past 6 months. CONCLUSIONS: Future interventions for this
      population may be strengthened by addressing the importance of HIV primary care;
      empowering participants with respect to the health care system; and promoting
      linkages to case management, health insurance, and local housing programs.

PMID- 18089982
TI  - What we can learn from the INSPIRE Study about improving prevention and clinical
      care for injection drug users living with HIV.

PMID- 18089983
TI  - Results from a randomized controlled trial of a peer-mentoring intervention to
      reduce HIV transmission and increase access to care and adherence to HIV
      medications among HIV-seropositive injection drug users.
AB  - BACKGROUND: There is a lack of effective behavioral interventions for HIV
      positive injection drug users (IDUs). We sought to evaluate the efficacy of an
      intervention to reduce sexual and injection transmission risk behaviors and to
      increase utilization of medical care and adherence to HIV medications among this
      population. METHODS: HIV-positive IDUs (n=966) recruited in 4 US cities were
      randomly assigned to a 10-session peer mentoring intervention or to an 8-session
      video discussion intervention (control condition). Participants completed audio
      computer-assisted self-interviews and had their blood drawn to measure CD4 cell
      count and viral load at baseline and at 3-month (no blood), 6-month, and 12-month
      follow-ups. RESULTS: Overall retention rates for randomized participants were
      87%, 83%, and 85% at 3, 6, and 12 months, respectively. Participants in both
      conditions reported significant reductions from baseline in injection and sexual
      transmission risk behaviors, but there were no significant differences between
      conditions. Participants in both conditions reported no change in medical care
      and adherence, and there were no significant differences between conditions.
      CONCLUSIONS: Both interventions led to decreases in risk behaviors but no changes
      in medical outcomes. The characteristics of the trial that may have contributed
      to these results are examined, and directions for future research are identified.

PMID- 18089984
TI  - Acceptability of A-CASI by HIV-positive IDUs in a multisite, randomized,
      controlled trial of behavioral intervention (INSPIRE).
AB  - Audio computer-assisted self-interviewing (A-CASI) is now widely used to gather
      information from many types of research participants, including injection drug
      users (IDUs). The purpose of this study was to describe how HIV-positive IDUs
      participating in an intervention trial viewed A-CASI and to identify the
      characteristics of participants who held unfavorable attitudes toward A-CASI.
      Using a sample of participants who completed 12-month assessments (n=821), we
      found that most (>80%) of the sample held favorable or neutral attitudes toward A
      CASI. Approximately 18% said that they would prefer an interview with a person to
      a computer, 12% said that they did not understand the questions they heard on the
      computer, and 14% said that the computer made it hard to be open and honest about
      risk behavior. Multivariate analyses found that participants who were more
      socially marginalized (with unstable housing and lower sense of empowerment) and
      had greater physical limitations and lower CD4 cell counts were consistently more
      likely to report various negative A-CASI attitudes; however, some outcome
      specific findings were also noted. Our research supports the feasibility and
      general acceptability of A-CASI with HIV-positive IDUs, and it suggests further
      research exploring the associations between A-CASI attitudes and characteristics
      of disadvantaged populations.

PMID- 18089985
TI  - Participants' descriptions of social support within a multisite intervention for
      HIV-seropositive injection drug users (INSPIRE).
AB  - HIV-positive injection drug users (IDUs) are at risk for transmitting HIV to
      their sex and injection partners, and compared with non-IDUs, they have poorer
      access to medical care and adherence to antiretroviral therapies. Social support
      has been linked with decreased injection and sexual risk behaviors and slower
      disease progression. In this qualitative process evaluation, we explored
      emotional support (ie, caring, empathy), informational support (ie, information,
      guidance, feedback), and appraisal support (ie, information for self-evaluation
      or understanding) received by participants in the Interventions for Seropositive
      Injectors-Research and Evaluation (INSPIRE) project, a multisite secondary
      prevention intervention for HIV-positive IDUs. Participants in the intervention
      and control conditions (N=40) described similar experiences in terms of type,
      source, and perceived benefits of social support received from the program.
      Emotional support was received from program staff, other participants, and
      elements of the intervention. Participants also mentioned social support received
      from the INSPIRE project in relation to changes they had made in their lives
      during and after their involvement in the intervention, such as changes in their
      drug use, sexual practices, and health care utilization.

PMID- 18089986
TI  - Factors associated with antiretroviral therapy adherence and medication errors
      among HIV-infected injection drug users.
AB  - BACKGROUND: Active drug use is often associated with poor adherence, but few
      studies have determined psychosocial correlates of adherence in injection drug
      users (IDUs). METHODS: Of 1161 Intervention for Seropositive Injectors-Research
      and Evaluation study enrollees, 636 were taking antiretrovirals. We assessed self
      reported adherence to self-reported antiretroviral regimens and medication
      errors, which we defined as daily doses that were inconsistent with standard or
      alternative antiretroviral prescriptions. RESULTS: Most subjects (75%, n=477)
      self-reported good (>or=90%) adherence, which was strongly associated with an
      undetectable viral load. Good adherence was independently associated with being a
      high school graduate, not sharing injection equipment, fewer depressive symptoms,
      positive attitudes toward antiretrovirals, higher self-efficacy for taking
      antiretrovirals as prescribed, and greater sense of responsibility to protect
      others from HIV. Medication errors were made by 54% (n=346) and were strongly
      associated with a detectable viral load and fewer CD4 cells. Errors were
      independently associated with nonwhite race and with depressive symptoms, poorer
      self-efficacy for safer drug use, and worse attitudes toward HIV medications.
      CONCLUSIONS: Modifiable factors associated with poor adherence, including
      depressive symptoms and poor self-efficacy, should be targeted for intervention.
      Because medication errors are prevalent and associated with a detectable viral
      load and fewer CD4 cells, interventions should include particular efforts to
      identify medication taking inconsistent with antiretroviral prescriptions.

PMID- 18089987
TI  - Correlates of lending needles/syringes among HIV-seropositive injection drug
      users.
AB  - Among HIV-positive injection drug users (IDUs), we examined the correlates of
      lending needles/syringes with HIV-negative and unknown status injection partners.
      HIV-positive IDUs (N=738) from 4 cities in the United States who reported
      injection drug use with other IDUs in the past 3 months participated in an audio
      computer-assisted self-administered interview. Eighteen percent of study
      participants self-reported having lent their needles to HIV-negative or unknown
      status injection partners. Multivariate analyses showed that 6 variables were
      significantly associated with this high-risk injecting practice. Older IDUs, high
      school graduates, and those reporting more supportive peer norms for safer drug
      use were less likely to lend needles/syringes. Admission to a hospital for drug
      treatment in the past 6 months, having injected with >1 person in the past 3
      months, and having more psychiatric symptoms were all associated with more risk.
      These findings underscore the need for a continued prevention focus on HIV
      positive IDUs that recognizes the combination of drug use, mental health factors,
      and social factors that might affect this high-risk injecting practice, which
      could be associated with HIV and hepatitis C transmission.

PMID- 18089988
TI  - Sexual transmission risk behavior reported among behaviorally bisexual HIV
      positive injection drug-using men.
AB  - BACKGROUND: Few research studies have examined the HIV transmission risk
      behaviors of HIV-positive injection drug users (IDUs) who are men who have sex
      with men and women (MSMW). METHODS: We compared unprotected vaginal or anal sex
      with an HIV-negative or unknown (UNK) status sexual partner of MSMW (n=118) with
      men who have sex exclusively with women (MSW; n=469) and men who have sex
      exclusively with men (MSM; n=90) using baseline information from the Intervention
      for Seropositive Injectors-Research and Evaluation (INSPIRE) study, a 4-city
      randomized controlled trial. RESULTS: MSMW were twice as likely to report
      unprotected vaginal sex (P<0.001) and 3 times as likely to report unprotected
      anal sex with an HIV-negative/UNK status female partner (P<0.001) as MSW. MSMW
      did not differ in their report of unprotected insertive anal sex and were half as
      likely to report unprotected receptive anal sex with HIV-negative/UNK status men
      (P=0.02) as MSM. MSMW were 2 times as likely to report engaging in transactional
      sex (buying or selling sex in exchange for money, drugs, or housing) than MSM or
      MSW (81%, 43%, and 36%, respectively; P<0.001). CONCLUSIONS: Further research is
      needed to understand the contexts of unprotected sex among HIV-positive injection
      drug-using MSMW. Prevention programs should target the unique prevention needs of
      this population, particularly their risk with female partners.

PMID- 18089989
TI  - Are feelings of responsibility to limit the sexual transmission of HIV associated
      with safer sex among HIV-positive injection drug users?
AB  - We developed a scale among HIV-positive injection drug users (IDUs) to measure
      self-perceived responsibility to limit HIV transmission during sex. We describe
      the characteristics of HIV-positive IDUs (n=1114, 62% male, HIV-positive for 9
      years on average) who felt responsible for protecting their sexual partners from
      HIV and evaluated whether such feelings were associated with safer sexual
      practices. Using this scale (Cronbach alpha=0.83) and audio computer-assisted
      self-interviewing technology, 75% of this sample felt responsible for protecting
      their sexual partners from HIV. In cross-sectional multivariate analysis, HIV
      positive IDUs who felt responsible were those with greater HIV knowledge
      (adjusted odds ratio [95% confidence interval]: 1.74 [1.26 to 2.40]), perceived
      social support (1.77 [1.28 to 2.44]), self-efficacy for safely injecting (1.41
      [1.02 to 1.94]), and self-efficacy for using condoms (1.92 [1.38 to 2.68]).
      Feeling responsible was associated with having relatively fewer sex partners (<10
      vs. >or=10, 0.57 [0.34 to 0.96]) and a lower odds of unprotected sex (0.63 [0.45
      to 0.89]) but was not associated with safer injection practices. Feelings of
      responsibility did not vary by demographic characteristics, suggesting that
      prevention messages that encourage HIV-positive people to play a role in curbing
      HIV transmission may be acceptable to many HIV-positive IDUs. Working with HIV
      positive IDUs to increase or reinforce feelings of responsibility may reduce the
      sexual transmission of HIV.

PMID- 18089990
TI  - Correlates of depression among HIV-positive women and men who inject drugs.
AB  - INTRODUCTION: Although depression is common among HIV-positive injection drug
      users (IDUs), little is known about differences between male and female HIV
      positive IDUs. METHODS: We used baseline data for 1126 HIV-positive IDUs from a
      behavioral intervention trial from 2001 through 2005 in 4 US cities. Using the
      Brief Symptom Inventory-18, scores indicating high risk for depression were
      calculated separately for men and women based on raw scores of 9 for women and 7
      for men. We did separate logistic regressions for men and women to evaluate
      correlates of depression in 4 domains: sociodemographic, psychosocial, substance
      use, and sexual behaviors/attitudes. RESULTS: Approximately one third of women
      and men met the criteria for being at high risk of depression. Women reported
      significantly more depressive symptoms than men. Correlates linked with
      depression for both genders included perceived functional limitation, greater
      negative feelings regarding condom use, lower social support, and lower sense of
      empowerment. Being physically abused as adults and being Hispanic were correlates
      specific to men. No unique correlate was identified for women. DISCUSSION:
      Because of the high prevalence of depression among HIV-positive IDUs, caregivers
      should screen HIV-positive IDUs for depression and consider treatment for
      depression. Because of the similarities in correlates of depression among men and
      women, case finding and interventions for depression are likely to be similar for
      male and female HIV-positive IDUs.

PMID- 18089994
TI  - Cardiac BB gun injury with missile embolus to the lung.

PMID- 18089995
TI  - Splenic rupture as an unusual cause of massive hematemesis.

PMID- 18089996
TI  - Anterior and posterior fixation of a cervical fracture induced by chiropractic
      spinal manipulation in ankylosing spondylitis: a case report.

PMID- 18089997
TI  - Coagulopathic patients with traumatic intracranial bleeding: defining the role of
      recombinant factor VIIa.
AB  - BACKGROUND: The combination of coagulopathy and intracranial bleeding (ICB) is a
      well-recognized cause of morbidity and mortality in the neurosurgical patient
      because of the risk of hematoma expansion. Although recombinant factor VIIa
      (rFVIIa) has been shown to be useful in intracerebral hemorrhage, its use in
      other forms of ICB such as subdural hematomas (SDHs) has rarely been described.
      METHODS: The clinical and laboratory features of a prospectively followed up case
      series of 15 patients with traumatic ICB (mainly isolated SDHs) and coagulopathy
      international normalized ratio (INR) >1.3 treated with rFVIIa in our institution
      are presented, along with a review of the literature regarding the role of rFVIIa
      in neurosurgical patients with ICB. RESULTS: All 15 patients suffered a SDH (4 of
      15 had a combined ICB) and coagulopathy (mean INR, 2.34 +/- 0.83;
      thrombocytopenia rate, 20%), which was attributed to anticoagulants in 46.7%. The
      mean INR decreased to 1.5 +/- 0.14 after standard therapy and 0.92 +/- 0.1 after
      rFVIIa therapy. There was no evident progression of bleeding in any patient
      treated with rFVIIa. In three patients, neurosurgery was obviated by rFVIIa
      therapy, whereas the other 12 patients underwent neurosurgery safely and
      successfully. None required subsequent surgery for continuing hemorrhage, and no
      adverse events secondary to FVIIa administration were observed. Based on our
      experience and the reviewed literature, a proposed algorithm for a stratified
      approach to rFVIIa administration in traumatic ICB is discussed. CONCLUSIONS:
      rFVIIa is an inducer of hemostasis, which successfully controlled potentially
      devastating bleeding in all of 15 coagulopathic neurosurgical patients with ICB.
      The use of rFVIIa lowered the INR into the operable range in all patients,
      allowing surgery, and in some cases, obviated the need for surgery. Randomized,
      placebo-controlled clinical trials are needed to further assess the efficacy and
      cost-effectiveness of this approach in this setting.

PMID- 18089998
TI  - Alveolar interleukin-10 regulates neutrophil apoptosis in severely traumatized
      patients.
AB  - BACKGROUND: The lung produces a localized immunologic response to systemic
      trauma, characterized by an initial proinflammatory period with production of
      interleukin (IL)-8 and IL-18, followed by an anti-inflammatory phase with
      elevated levels of IL-10. Recent studies have shown a correlation between
      alveolar IL-10 and the rate of local neutrophil apoptosis. The aim of the present
      study was to further characterize the association of alveolar IL-8 and IL-10
      after trauma with neutrophil activation, apoptosis, and phagocytic capacity.
      METHODS: Bronchoalveolar lavage fluid (BALF) was obtained from 17 trauma patients
      with an Injury Severity Score >/=16 who required mechanical ventilation.
      Neutrophils from venous blood of healthy volunteers were incubated in either (1)
      cell culture media (control), (2) culture media + BALF, (3) culture media + BALF
      + anti-IL-8 neutralizing antibody, or (4) culture media + BALF + anti-IL-10.
      Surface CD11b expression, ability to phagocytose fluorescent bacteria, and
      neutrophil apoptosis were determined by flow cytometry. RESULTS: Phagocytosis and
      CD11b expression were both augmented on postinjury day 1 when compared with
      controls. Neutralization of IL-10 or IL-8 produced no significant differences in
      phagocytosis or CD11b expression. However, neutralization of IL-10 significantly
      decreased the rate of apoptosis in samples from postinjury day 1. CONCLUSION:
      Phagocytosis and CD11b expression on neutrophils are IL-8 and IL-10 independent.
      However, our data indicate that alveolar neutrophil apoptosis is dependent on IL
      10 at early time points after injury. Elucidation of this pathway may allow novel
      interventions to prevent posttraumatic pulmonary dysfunction.

PMID- 18089999
TI  - Toll-like receptor 2 and 4 expression after severe injury is not involved in the
      dysregulation of the innate immune system.
AB  - BACKGROUND: Severe injury after trauma is associated with a diminished production
      of different proinflammatory cytokines after stimulation with bacterial cell wall
      components. The cellular mechanisms, leading to a decreased responsiveness
      especially of monocytes after multiple injuries have not yet been elucidated in
      detail. The expression of Toll-like receptors (TLR) on leukocytes is essential
      for recognition of bacterial components. We investigated the expression of TLR2
      and 4 in correlation with gram-negative and gram-positive stimuli-dependent
      cytokine liberation after severe injury in comparison with that in healthy
      volunteers. METHODS: In a prospective clinical experimental study, 12 trauma
      patients with an Injury Severity Score above 21 points and 14 healthy volunteers
      were analyzed. Heparinized whole blood samples of patients were collected within
      48 hours after trauma and incubated in vitro with or without lipopolysaccharide
      (LPS) and peptidoglycan (PGN). TLR2 and TLR4 expression on monocytes was analyzed
      by flow cytometry. LPS- and PGN-induced tumor necrosis factor alpha (TNFalpha)
      and interleukin-8 production was measured by means of enzyme-linked immunosorbent
      assay. RESULTS: Both LPS- and PGN-induced TNFalpha liberation were significantly
      reduced in severely injured patients. The surface expression of TLR2 was also
      significantly decreased on monocytes collected from trauma patients, whereas the
      expression of TLR4 remained unchanged. There was only a negative correlation
      between TLR2 expression and the liberation of TNFalpha after stimulation with LPS
      or PGN. CONCLUSIONS: We conclude that diminished cytokine production after trauma
      cannot be explained simply by changes in TLR2 or TLR4 expression and that
      subsequent signaling cascades or additional receptors are involved in the blunted
      cytokine response after trauma.

PMID- 18090000
TI  - B-type natriuretic peptide levels may be elevated in the critically injured
      trauma patient without congestive heart failure.
AB  - BACKGROUND: Rapid diagnosis of congestive heart failure (CHF) is essential to
      treatment. B-type natriuretic peptide (BNP) is a neurohormone secreted by the
      heart in response to fluid overload and has been shown to be elevated in medical
      patients with left ventricular dysfunction. However, BNP has not been evaluated
      in the critically ill patient with trauma. METHODS: Trauma patients of at least
      18 years of age with an expected intensive care unit stay of at least 24 hours
      were studied. Patients had BNP measurements at admission and at 24 hours and 48
      hours. Echocardiography was performed within 48 hours of admission. CHF was
      determined by echocardiographic findings of systolic or diastolic dysfunction.
      Elevated BNP levels were defined as those greater than 100 pg/mL. A Fisher's
      exact test was performed to determine whether a relationship between BNP levels
      and echocardiographic findings existed. Linear correlation was used to determine
      whether BNP correlated with echocardiographic findings and initial Glasgow Coma
      Scores. RESULTS: Fifty patients were included in the analysis. There was no
      relationship between elevated BNP levels and echocardiographic evidence of CHF (p
      = 0.149). There was no threshold value above which CHF was present. There were 28
      patients with head injuries, and no relationship between BNP levels and CHF could
      be found (p = 0.432) in this group. CONCLUSION: Our data show no association
      between BNP and CHF in the critically ill patient with trauma. BNP levels may be
      elevated in patients with head injuries without echocardiographic evidence of
      CHF.

PMID- 18090001
TI  - Continuous hemofiltration in hyperthermic septic shock patients.
AB  - BACKGROUND: Severe hyperthermia commonly accompanies septic shock. High body
      temperature in absence of infection activates the inflammatory response and is
      associated with a high mortality. Three years ago, our hypothesis that sustained
      fever is harmful in septic shock led us to the development of a protocol aiming
      at decreasing hyperthermia (>/=39.5 degrees C) by means of hemofiltration when
      the patients did not respond to antipyretics. We present a report of temperature
      and hemodynamic changes and the outcome of 19 consecutive hyperthermic septic
      shock patients with multiorgan system failure and compare them with a historical
      similar group of patients in whom hyperthermia was not treated with
      hemofiltration. METHODS: Depending on renal function, patients were treated with
      continuous low-flow hemofiltration (n = 8) or hemodiafiltration, (n = 11). Core
      temperature was registered every hour. A hemodynamic index (HI) was defined (mean
      arterial pressure to noradrenaline dose) and used during the first 24 hours to
      describe the patients' hemodynamic profile by means of its percent variation
      starting 6 hours before instituting the hemofiltration. RESULTS: The patients'
      temperature decreased linearly from 39.8 degrees C +/- 0.5 degrees C before
      hemofiltration to 37 degrees C +/- 1.2 degrees C after 24 hours of treatment (p <
      0.001). The HI decreased significantly from -6 hours to the onset of
      hemofiltration (p = 0.002) and increased significantly after 24 hours (p =
      0.008). Twenty-eight-day mortality was 32% (6 of 19) when compared with 100% (11
      of 11) in the historical group (p < 0.001). CONCLUSIONS: Continuous low-flow
      hemofiltration decreased body temperature and vasopressor requirements in
      hyperthermic septic shock patients. The mortality was unexpectedly low.

PMID- 18090002
TI  - The value of indicated computed tomography scan of the chest and abdomen in
      addition to the conventional radiologic work-up for blunt trauma patients.
AB  - BACKGROUND: Multidetector computed tomography (CT) is more sensitive and specific
      in detecting traumatic injuries than conventional radiology is. However, still
      little is known about the diagnostic value and the therapeutic impact of
      indicated thoraco-abdominal CT scan when it is performed in addition to the
      complete conventional radiologic work-up for blunt trauma patients. METHODS:
      Clinical and radiologic data from 106 consecutive blunt trauma patients were
      reviewed. Diagnoses revealed by conventional work-up of the chest, abdomen,
      pelvis, and thoracolumbar spine were compared with that detected by CT scan of
      the chest and abdomen. Unexpected findings by CT scan and rejected diagnoses by
      CT scan were collected. Therapeutic consequences of these diagnoses were
      determined both theoretically and collected from the medical records. RESULTS: In
      74% (95% confidence interval [CI] 65-82) of the 106 patients, 1 or more diagnoses
      were demonstrated by chest or abdominal CT scan, whereas they had not been
      revealed by preceding conventional work-up. This resulted in an actual change of
      treatment in 34% (95% CI 25-43) of the patients. CT scan of the chest resulted in
      a change of treatment in 33% (95% CI 23-44) and abdominal CT scan in 16% (95% CI
      9-24). CONCLUSIONS: CT scan of the chest and abdomen has a high diagnostic value
      in the evaluation of blunt trauma patients, when it is selectively performed in
      addition to the early conventional radiologic work-up. Unexpected pathologic
      findings are detected by CT scan in the majority of the patients. These findings
      result in an adaptation of treatment in a substantial number of the patients.

PMID- 18090003
TI  - The increasing use of vena cava filters in adult trauma victims: data from the
      American College of Surgeons National Trauma Data Bank.
AB  - BACKGROUND: Vena cava filters (VCFs) have been advocated for prophylaxis of
      pulmonary embolism in trauma patients at high risk for venous thrombosis in whom
      anticoagulation is contraindicated or not feasible. We sought to determine the
      frequency of VCF insertion and patterns of use in trauma patients using a large
      database. METHODS: Retrospective analysis of data from the National Trauma Data
      Bank of the American College of Surgeons on patients over the age of 17 years
      from 1991 to 2002. We examined the annual frequency of VCF placement, the
      demographics and injury severity of patients receiving them, and the
      characteristics of the hospitals at which they were being placed. RESULTS: Of
      614,349 patients, 6,282 received a VCF (1%); 86% were placed prophylactically
      (without an associated discharge diagnosis of either pulmonary embolism or venous
      thrombosis). Filter use increased significantly from 0.3% of patients in 1994 to
      1.2% in 2002 (p < 0.001). There was substantial variation in clinical practice
      with regard to placement of VCF according to injury type and its perceived risk
      of venous thromboembolism. VCFs were placed significantly more frequently at
      hospitals verified as Level I trauma centers. CONCLUSION: VCF insertion has
      increased significantly during the past 10 years in trauma patients reported to
      the National Trauma Data Bank. The lack of an evidence-based guideline for their
      use has resulted in a wide variation in practice. Such variation in practice
      indicates the need for a consensus conference or a multicenter prospective
      clinical trial to determine their role in trauma patients.

PMID- 18090004
TI  - The effects of ethanol on beta2-integrin and l-selectin on the surface of
      leukocytes in human whole blood.
AB  - BACKGROUND: Acute alcohol intoxication is associated with increased
      susceptibility to infection. In host defense, the expression of adhesion
      molecules such as beta2-integrin and l-selectin on leukocytes is involved in
      leukocyte migration to inflamed organ tissue. To elucidate the mechanisms
      underlying the immunosuppressive effects of ethanol, we investigated whether
      ethanol pretreatment may influence the changes in adhesion molecule expression
      induced by lipopolysaccharide (LPS) or interleukin (IL)-8 in human whole blood.
      METHODS: Ethanol was added to samples of human whole blood (final concentration:
      0%, 0.2%, 0.4%, and 0.8%). Samples were assigned to an unstimulated group and an
      LPS-stimulated group. In another set of experiments, stimulation was induced by
      IL-8. After fluorescence labeling of alphaM-subunit of beta2-integrin (CD11b) and
      l-selectin (CD62L), the expression of CD11b and CD62L were measured using flow
      cytometry. RESULTS: Stimulation with LPS significantly upregulated CD11b
      expression (5.9 +/- 0.9 to 16.3 +/- 1.8, p < 0.05). Ethanol inhibited this LPS
      induced upregulation of CD11b (p < 0.001). Stimulation with IL-8 significantly
      upregulated CD11b expression (5.3 +/- 1.7 to 7.5 +/- 2.7, p < 0.01) and this IL-8
      induced upregulation of CD11b was also inhibited by ethanol pretreatment (p <
      0.001). In contrast, ethanol did not modify CD62L expression in either
      unstimulated or stimulated groups. CONCLUSION: The impairment of CD11b expression
      on leukocytes suggests that alcohol intake interferes with the migration of
      leukocytes to sites of inflammation, which may explain, in part, why alcohol
      intoxication increases susceptibility to infection.

PMID- 18090005
TI  - Comparative efficacy of granular and bagged formulations of the hemostatic agent
      QuikClot.
AB  - BACKGROUND: QuikClot is a zeolite-based dressing approved and deployed by
      military for the arrest of severe combat-induced hemorrhage. A novel formulation
      (bagged QuikClot [ACS]) of the original granular QuikClot (QC) has been proposed
      to facilitate the application of the hemostatic dressings under battlefield
      conditions. This study compares the hemostatic efficacy of ACS and QC in
      controlling blood loss and improving survival in a swine model of uncontrolled
      hemorrhage induced by complex groin injury. METHODS: After transection of the
      femoral vasculature, anesthetized Yorkshire pigs (n = 32) were hemorrhaged for 3
      minutes and randomized into four groups: no treatment (NONE) or application of
      standard dressing (SD), QC, or ACS. At 15 minutes, resuscitation was initiated by
      infusion of 500 mL Hextend during a span of 30 minutes. Vital signs were
      continuously recorded throughout the 4-hour experimental period. In addition,
      blood loss and temperature at the dressing and tissue interface were continuously
      recorded. RESULTS: After 3 minutes, average blood loss was 44.7% +/- 11.9%
      estimated blood volume (EBV) for all animals (34.1 +/- 3.2 kg). Posttreatment
      blood loss was significantly higher (p < 0.01) for NONE- and SD-treated animals
      (31.5% +/- 21.8% and 22.3% +/- 12.6% EBV, respectively) as compared with animals
      treated with QC and ACS (7.4% +/- 7.1% and 10.3% +/- 6.9%, respectively). All
      NONE animals died at approximately 60 minutes. Times until death were slightly
      greater for animals treated with SD (96.8 minutes) and significantly greater for
      animals treated with QC (188 minutes) and ACS (194 minutes). Overall survival to
      4 hours for SD (1 of 8, 12.5%) was significantly lower (p < 0.02) than for QC (6
      of 8, 75%) and for ACS (6 of 8, 75%) treatments. Elevated temperatures at the
      dressing and tissue interface were seen in animals treated with QC and ACS
      (average at 8 minutes was 58.1 +/- 4.5 degrees C and 58.2 +/- 5.3 degrees C,
      respectively) compared with SD treated animals (38.8 +/- 2.7 degrees C).
      Histologic examination revealed more edema in muscular tissue of animals treated
      with ACS as compared with in QC-treated animals. CONCLUSIONS: ACS was as
      efficacious as original granular QC in inducing hemostasis and improving survival
      as compared with the efficacy of SD. Easier and more rapid application and
      complete removal of ACS may offer a distinct advantage in battlefield
      resuscitation efforts to enhance a clean wound site and eventual surgical repair.

PMID- 18090006
TI  - Hemostatic efficacy of a recombinant thrombin-coated polyglycolic acid sheet
      coupled with liquid fibrinogen, evaluated in a canine model of pulmonary arterial
      hemorrhage.
AB  - BACKGROUND: In thoracic surgery, although infrequent, we encounter unexpected
      damage to the pulmonary artery (PA). In the present study, we evaluated the
      hemostatic efficacy of a newly developed fibrin-based sheet material, thrombin
      sheet, coupled with liquid fibrinogen (TSF), in an experimental model of PA
      hemorrhage. METHODS: Female beagles (n = 8) were used for the study. Left
      thoracotomy was performed under general anesthesia. PA injury (approximately 4 x
      2 mm) was created, and repaired by TSF (TSF group) or TachoComb (TC group). The
      animals were allowed to survive, and the repaired site was evaluated 4 weeks
      after the experiment. RESULTS: The number of sheet application and compression
      procedures required for hemostasis was increased in the TC group compared with in
      the TSF group (TC vs. TSF, 4 +/- 1 vs. 1 +/- 0.5, p = 0.01, unpaired t test). The
      time required to achieve hemostasis was increased in the TC group compared with
      in the TSF group (TC vs. TSF, 7 +/- 3 vs. 1 +/- 0.5 minutes, p = 0.01, unpaired t
      test). The amount of bleeding during the hemostasis procedure was increased in
      the TC group compared with in the TSF group (TC vs. TSF, 48 +/- 22 vs. 3 +/- 3 g,
      p = 0.01, unpaired t test). At 4 weeks, rethoracotomy revealed no apparent
      indication of delayed bleeding, such as intrathoracic hematoma formation or
      excessive adhesion formation in the vicinity of PA, in either group.
      Histologically, the vessel lumen was well sustained in both groups, with no
      apparent stenosis or thrombus formation. CONCLUSION: The hemostatic efficacy of
      TSF was superior to TC in this particular experiment. Single application of TSF
      was sufficient to achieve hemostasis in all but one animal. Compression time of
      approximately 1 minute was also very short albeit that the bleeding was from the
      PA and not an artery. These results were presumably because the adhesion was
      stronger, faster, and the sheet was more pliable in TSF compared with TC.

PMID- 18090007
TI  - Ischemic preconditioning prevents skeletal muscle tissue injury, but not nerve
      lesion upon tourniquet-induced ischemia.
AB  - BACKGROUND: Prolonged ischemia followed by reperfusion (I/R) of skeletal muscle
      results in significant tissue injury. Ischemic preconditioning (IPC), achieved by
      brief periods of ischemia before sustained ischemia, has been shown to ameliorate
      I/R injury in a variety of tissues. We demonstrate that tourniquet hind limb
      ischemia-induced injury of the muscle benefits from IPC, whereas the peripheral
      nerve suffers from prolonged ischemia time and mechanical deterioration on IPC.
      METHODS: In anesthetized rats, hind limb ischemia was induced by tourniquet for 3
      hours followed by 24 hours of reperfusion. In an additional series of
      experiments, IPC (three cycles of 10 minutes I/10 minutes R) preceded hind limb
      ischemia. Sham-operated animals without ischemia served as controls. Skeletal
      muscle tissue injury was assessed with respect to microcirculation, inflammatory
      cell response, and cell integrity using intravital fluorescence microscopy,
      Western blot protein analysis, and tissue histochemistry. Analysis of tactile and
      thermal allodynia served as indicators for postischemic pain. In addition, motor
      nerve conduction velocity and transmission electron microscopy allowed assessing
      postischemic nerve lesion. RESULTS: Tourniquet of the hind limb caused marked
      perfusion failure, enhanced leukocyte-endothelial cell interaction, and apoptotic
      cell death. IPC was able to improve microvascular perfusion and to reduce
      inflammatory cell response. Of interest, apoptotic cell death, assessed by cell
      nuclear morphology in vivo as well as Western blot and immunohistochemical
      analysis of caspase-3 cleavage, can be substantially reduced by IPC in tourniquet
      ischemia of the hind limb. Application of the tourniquet abolished nerve
      conduction in all animals. Non-IPC-treated animals still showed tactile
      allodynia, whereas IPC further caused loss of pain sensation and motor function
      of the postischemic hind limb. CONCLUSIONS: High susceptibility of the peripheral
      nerve to compression-induced ischemic injury disproves IPC in its clinical
      application for surgical procedures requiring prolonged tourniquet ischemia.

PMID- 18090008
TI  - Experimental study of controlled fluid resuscitation in the treatment of severe
      and uncontrolled hemorrhagic shock.
AB  - BACKGROUND: Hemorrhagic shock is a common clinic emergency case. The fluid
      resuscitation method in the presurgical care of hypotensive trauma patients is
      open to debate. This study was conducted to evaluate the general and
      pathophysiologic effects of controlled fluid resuscitation in the treatment of
      severe and uncontrolled hemorrhagic shock. METHODS: A model of rat with severe
      hemorrhagic shock and active bleeding was established in 32 Sprague-Dawley rats.
      The rats were randomly divided into the control group, no fluid resuscitation
      group (NF group), controlled fluid resuscitation group (NS40 group), and
      aggressive fluid resuscitation group (NS80 group). Each group contained eight
      rats. The changes of survival, blood loss, blood platelet, hemoglobin,
      hematocrit, and serum lactate level were dynamically monitored in the
      "prehospital phase". In addition, the apoptosis in the liver, kidney, lung, and
      small intestinal mucosa of survivors after hemorrhage and resuscitation was
      detected by light microscopy in hematoxylin-eosin stained tissue sections, flow
      cytometry, and terminal deoxynucleotidyl transferase dUTP nick end labeling. Via
      the above-mentioned indexes, the curative effects of three fluid resuscitation
      methods were compared. RESULTS: Compared with the survival in the NF group (3 of
      8), the higher survival rate of the NS40 and NS80 groups (14 of 16) showed
      significant difference (p < 0.05). After fluid resuscitation, serum lactate
      levels in the NS40 and NS80 groups obviously decreased (p < 0.01 compared with
      control and NF groups). The shed blood loss from bleeding tail in the NS80 group
      was obviously increased (p < 0.01 for the NS80 group compared with the control,
      NF, and NS40 groups). Compared with that of the control, NF, and NS40 groups, the
      hemoglobin, hematocrit, and blood platelet of the NS80 group quickly descended in
      the prehospital phase and showed statistical differences. At the same time, there
      was some apoptosis in the liver, kidney, lung, and small intestinal mucosa of all
      survivors. Compared with that of the NF and NS40 groups, the apoptosis of liver,
      kidney, and small intestinal mucosa of the NS80 group was obviously increased,
      and showed statistical differences. CONCLUSIONS: In severe and uncontrolled
      hemorrhagic shock, some fluid must be given in proper time to improve tissue
      perfusion and avoid early death. Among three fluid resuscitation methods,
      controlled fluid resuscitation can effectively decrease additional blood loss,
      avoid excessive hemodilution and coagulopathy, improve the early survival rate,
      and reduce the apoptosis of visceral organs in rats with severe and uncontrolled
      hemorrhagic shock. This model supports the concept that when surgical care is not
      readily available, controlled fluid resuscitation should be considered in the
      treatment of uncontrolled hemorrhagic shock.

PMID- 18090009
TI  - The ratio of blood products transfused affects mortality in patients receiving
      massive transfusions at a combat support hospital.
AB  - BACKGROUND: Patients with severe traumatic injuries often present with
      coagulopathy and require massive transfusion. The risk of death from hemorrhagic
      shock increases in this population. To treat the coagulopathy of trauma, some
      have suggested early, aggressive correction using a 1:1 ratio of plasma to red
      blood cell (RBC) units. METHODS: We performed a retrospective chart review of 246
      patients at a US Army combat support hospital, each of who received a massive
      transfusion (>/=10 units of RBCs in 24 hours). Three groups of patients were
      constructed according to the plasma to RBC ratio transfused during massive
      transfusion. Mortality rates and the cause of death were compared among groups.
      RESULTS: For the low ratio group the plasma to RBC median ratio was 1:8
      (interquartile range, 0:12-1:5), for the medium ratio group, 1:2.5 (interquartile
      range, 1:3.0-1:2.3), and for the high ratio group, 1:1.4 (interquartile range,
      1:1.7-1:1.2) (p < 0.001). Median Injury Severity Score (ISS) was 18 for all
      groups (interquartile range, 14-25). For low, medium, and high plasma to RBC
      ratios, overall mortality rates were 65%, 34%, and 19%, (p < 0.001); and
      hemorrhage mortality rates were 92.5%, 78%, and 37%, respectively, (p < 0.001).
      Upon logistic regression, plasma to RBC ratio was independently associated with
      survival (odds ratio 8.6, 95% confidence interval 2.1-35.2). CONCLUSIONS: In
      patients with combat-related trauma requiring massive transfusion, a high 1:1.4
      plasma to RBC ratio is independently associated with improved survival to
      hospital discharge, primarily by decreasing death from hemorrhage. For practical
      purposes, massive transfusion protocols should utilize a 1:1 ratio of plasma to
      RBCs for all patients who are hypocoagulable with traumatic injuries.

PMID- 18090010
TI  - Assessment of adverse events in the demise of pediatric burn patients.
AB  - BACKGROUND: Given the contention that survival is to be expected from even the
      most severely burned child, then, intuitively, at least some pediatric burn
      victims die because of suboptimal care. The purpose of this study is to assess
      the impact of any adverse events that may have contributed to the death of burned
      children. METHODS: Four surgeons with specialty training in pediatric burn care
      reviewed the clinical course and autopsy findings of 71 burned children who died
      after admission to a burn center during a 10-year interval. Reviewers were asked
      to determine the predominant factor or factors contributing to each child's
      demise and to assess the significance of any deviations from optimal care.
      RESULTS: For the 10 years under review, overall mortality for all pediatric burns
      was 2.4%. Of these deaths, 25% had burns encompassing less than 50% body surface
      area. The reviewers identified lung damage as the most frequent cause of death,
      which was deemed largely unpreventable. Conversely, hypovolemia related to
      inadequate prehospital fluid resuscitation and failure to obtain and maintain a
      patent airway were considered the second and third most common factors in a
      child's death and deemed preventable under ideal circumstances. CONCLUSIONS: This
      review implies that deficiencies in health care contribute to the demise of many
      burned children. The most notable areas for improvement are in fluid
      resuscitation and airway control. This suggests that quality assurance and
      educational initiatives to improve these aspects of care may have the greatest
      impact on further improving survival of burned children.

PMID- 18090011
TI  - A fentanyl-based pain management protocol provides early analgesia for adult
      trauma patients.
AB  - BACKGROUND: In the past two decades, a number of reports have identified
      inadequate treatment of pain among emergency department patients. No study has
      evaluated the frequency or effectiveness of early analgesia in the trauma
      patient. The objective of this study was to determine the effect of a protocol
      driven pain management scheme on time to initiation of analgesia among trauma
      patients. METHODS: A fentanyl-based protocol was developed with patients being
      assigned to one of three treatment arms based on hemodynamics and Glasgow Coma
      Scale (GCS) score. Using an institutional review board-approved before and after
      study design, patients over the age of 14 and meeting trauma system activation
      criteria at the Dartmouth-Hitchcock Medical Center were eligible. Results were
      compared with a retrospective chart review of eligible patients treated during a
      matched preprotocol time period in 2002. The primary outcome measure was time to
      initiation of analgesia. Secondary outcome measures included (1) the proportion
      of patients receiving their first analgesia dose within 30 minutes, (2) the
      number of patients receiving multiple doses of analgesia in the trauma bay, and
      (3) adverse events. Pain level was assessed using either a Numeric Pain Scale
      (for patients with a GCS score of 15) or a Behavioral Pain Assessment Scale (GCS
      score <15). RESULTS: Implementation of the protocol resulted in a decrease in the
      mean time to initiation of analgesia from 53.61 minutes +/- 6.88 minutes to 27.94
      minutes +/- 3.34 minutes (p = 0.001). The protocol also increased the percentage
      of patients receiving analgesia within the first 30 minutes of arrival from 44.4%
      to 74.6% (p < 0.001). There were no differences between the two groups in terms
      of baseline characteristics or adverse events. CONCLUSIONS: The implementation of
      a fentanyl-based pain management protocol resulted in a marked reduction in time
      to initial analgesia among trauma patients. There was no evidence of an increase
      in adverse events. This tool has the potential to be easily extrapolated and
      applied to other trauma systems.

PMID- 18090012
TI  - Transarterial embolization for intractable oronasal hemorrhage associated with
      craniofacial trauma: evaluation of prognostic factors.
AB  - BACKGROUND: This study analyzed the outcomes for clinical application of
      transarterial embolization (TAE) to treat intractable posttraumatic oronasal
      hemorrhage in patients who suffered from craniofacial injuries. METHODS: The
      charts and radiologic and operative records of 34 patients from January 2002 to
      December 2007 were retrospectively reviewed. Inclusion criteria focused on the
      patients whose intractable posttraumatic oronasal hemorrhage associated with
      craniofacial trauma required TAE treatment. The patients' survival was correlated
      with prognostic factors with Spearman's rank correlation coefficients. Wilcoxon
      signed ranks test was used to analyze the differences between the severity of
      shock before and after TAE, and Fisher's exact test was used to analyze unvaried
      factors. RESULTS: TAE successfully stopped the posttraumatic oronasal hemorrhage
      in 27 of 34 patients (79.4%). The internal maxillary artery was the most common
      hemorrhaging vessel requiring embolization. Successful hemostasis by TAE
      significantly contributed to patient survival (p = 0.001). In addition, higher
      Glasgow Coma Scale score (>/=8) at presentation, lower shock index (calculated as
      heart rate/systolic blood pressure; </=1.1 and 0.8, before and after TAE,
      respectively), and injury severity score </=32 positively contributed to the
      patients' higher survival rate (p < 0.05). During the acute treatment of
      posttraumatic oronasal hemorrhage, need for craniotomy was not correlated with
      patient survival, but need for laparotomy to treat the second abdominal
      hemorrhagic source decreased the rate of patient survival (p = 0.023).
      CONCLUSION: TAE may stop intractable posttraumatic oronasal hemorrhage when
      conventional packing fails to achieve hemostasis. Glasgow Coma Scale score at
      presentation, shock index before and after TAE, injury severity score, and need
      for emergent laparotomy can be used to predict the patient prognosis.

PMID- 18090013
TI  - Concomitant injuries in patients with panfacial fractures.
AB  - BACKGROUND: Patients with panfacial fractures comprise a small portion of the
      overall facial fracture patient population. Because of the forces necessary to
      cause panfacial injury, these patients often have other concomitant injuries. The
      timing of operative facial fracture management remains controversial. METHODS: A
      3-year review of all patients with facial fractures was conducted at Duke
      University Medical Center (2003-2005, 437 total patients). All patients with
      panfacial fractures, defined as fractures involving at least three of the four
      facial segments (frontal, upper midface, lower midface, and mandible), were
      analyzed. RESULTS: Panfacial fractures were present in 38 patients (9% of overall
      facial fracture population). Twenty (53%) of these patients suffered concomitant
      injuries. The most common mechanism of trauma was motor vehicle collision, and
      the most common category of concomitant injury was intracranial injury or
      hemorrhage. Other commonly occurring categories of injury included abdominal
      organ injury, pneumothorax, pulmonary contusion, spine fracture, rib or sternum
      fracture, extremity fracture, and pelvic fractures. There was no significant
      difference in day of operation for the management of facial fractures between
      those with isolated facial injuries and those with other concomitant injuries
      (hospital day 2.1 vs. hospital day 2.9, not significant). CONCLUSIONS:
      Concomitant injuries to all parts of the body are found in patients with
      panfacial trauma. In our experience, these injuries do not significantly delay or
      have an adverse effect on the treatment of facial fractures. A treatment strategy
      for consistent timely management of facial fractures is described.

PMID- 18090014
TI  - Head, face, and neck injuries during Operation Iraqi Freedom II: results from the
      US Navy-Marine Corps Combat Trauma Registry.
AB  - BACKGROUND: Head, face, and neck injuries (HFNIs) are an important source of
      combat mortality and morbidity. The objective of this study was to document the
      characteristics and causes of HFNIs during Operation Iraqi Freedom II. METHODS: A
      retrospective review of HFNIs sustained by US military casualties between March
      1, 2004 and September 30, 2004 was performed. Data were collected from the Navy
      Marine Corps Combat Trauma Registry. RESULTS: During the study period, 39% of all
      injury casualties in the registry had HFNIs. Of the 445 HFNI patients, one-third
      presented with multiple wounds to the head, face, and neck. Four percent of
      battle HFNI patients died from wounds, and nearly 40% of the surviving wounded
      were evacuated for treatment. Improvised explosive devices (IEDs) were the most
      frequent cause of battle HFNIs. Nonbattle HFNIs were most often the result of
      motor vehicle crashes. The majority (65%) of all HFNIs were to the face. Head
      injuries, overall, were more severe than face or neck wounds according to the
      Abbreviated Injury Scale. CONCLUSIONS: The proportion of combat-related HFNIs is
      increasing and is primarily caused by IEDs. Improved protection for the
      vulnerable facial region is needed. Continued research on the changing nature of
      warfare and distribution of HFNIs is necessary to enhance the planning and
      delivery of combat casualty medical care.

PMID- 18090015
TI  - Marked improvement in adherence to traumatic brain injury guidelines in United
      States trauma centers.
AB  - BACKGROUND: Prior surveys of acute medical management of severe traumatic brain
      injury (TBI) indicate that care is fragmented and inconsistent, although
      Guidelines for the management of severe traumatic brain injury (guidelines) were
      distributed and endorsed by the American Association of Neurologic Surgeons. We
      conducted a survey of US trauma centers to evaluate guideline adherence, to
      examine predictors of adherence, and to compare our results with similar surveys
      conducted in 1991 and 2000. METHODS: A Web-based survey was conducted in 413
      designated trauma centers admitting patients with severe TBI. Good adherence was
      defined as adherence to the median number of guidelines (median = 6,
      interquartile range 5-7). RESULTS: In adjusted analysis, good adherence was
      predicted by Level I trauma center designation and presence of treatment
      protocols. Compared with trauma centers without these predictive factors, the
      likelihood of good guideline adherence increased 2.4-fold with each additional
      predictor (95% confidence interval = 1.8-3.3). Routine intracranial pressure
      monitor use increased from 32.4% in 1991 and 50.8% in 2000 to 77.4% in the
      current survey (p < 0.0001). Avoidance of steroids in TBI rose from 47.8% in 1991
      and 52.4% in 2000 to 86.0% in 2006 (p < 0.0001). Lack of guideline adherence
      decreased significantly from 67% in 2006 to 34.5%. CONCLUSIONS: Adherence to
      evidence-based guidelines for severe TBI has improved dramatically since 1991.
      Trauma center level and treatment protocols were associated with good adherence,
      suggesting that directing patients with severe TBI to Level I and Level II trauma
      centers with treatment protocols will improve outcome for these patients.

PMID- 18090016
TI  - The healing of tibial fracture and response of the local lymphatic system.
AB  - BACKGROUND: Damage of tissues by mechanical injury and inflammation is followed
      by reaction of the regional lymphoid tissue, lymphatics, and lymph nodes. In our
      previous lymphoscintigraphic studies, we showed that closed fractures of a lower
      limb cause reaction of the local lymphoid tissue. There was dilation of
      lymphatics draining the site of the fracture and enlargement of inguinal lymph
      nodes. These changes persisted even after clinical healing of the fracture. In
      the long-lasting nonhealing fractures, the lymphoscintigraphic pictures were
      different. The draining lymphatics became obliterated, and the lymph nodes
      disappeared. METHODS: In this study, we tried to correlate the
      lymphoscintigraphic images, reflecting the immune events at the fracture site,
      with the immunohistochemical observations of the biopsy specimens obtained during
      corrective operations from the healing and nonhealing fracture gaps. Thirty-eight
      patients with closed fracture of the tibia without traumatic skin changes were
      studied. RESULTS: We confirmed that closed tibial fracture evokes response of the
      regional lymphatic system. Normal fracture healing with immune cell infiltrates
      and foci of ossification was accompanied by dilated lymphatics and enlarged lymph
      nodes. Prolonged nonhealing fracture with lack of cellular reaction in the gap
      proceeded with decreased mass of lymph nodes. CONCLUSION: This study provides
      evidence for existence of a functional axis between wound of bone and surrounding
      soft tissue and the local lymphatic (immune) system. We hypothesize that the fast
      healing is regulated by influx into the wound of lymph node regulatory cells,
      whereas prolonged healing causes gradual exhaustion of the regional lymph node
      functional elements, and reciprocally impairment in sending regulatory cells to
      the fracture gap.

PMID- 18090017
TI  - Knee dislocations with vascular injury: outcomes in the Lower Extremity
      Assessment Project (LEAP) Study.
AB  - OBJECTIVES: The purpose of this study is to report the clinical and functional
      results of a cohort of patients with knee dislocations associated with vascular
      injury. METHODS: Patients with knee dislocation and associated vascular injury
      were prospectively assessed for outcome of severe lower extremity trauma during 2
      years. The Sickness Impact Profile was used to assess the functional recovery of
      the patient. Surgeon and therapist assessments documented clinical metrics and
      treatment, including salvage or amputation, neurologic recovery, knee stability,
      and knee motion. RESULTS: Eighteen patients sustained a knee dislocation and an
      associated popliteal artery injury. Seven patients were found to have an
      additional vascular injury. All patients underwent repair of the vascular injury.
      At the time of final follow-up, 14 knees were successfully salvaged and four
      required amputation (1 below knee amputation, 2 through knee amputation, and 1
      above knee amputation). Eighteen patients had at least a popliteal injury and
      underwent repair of the vascular injury. The patients with a limb-threatening
      knee dislocation that was successfully reconstructed had Sickness Impact Profile
      scores of 20.12 at 3 months, 13.18 at 6 months, 12.08 at 1 year, and 7.0 at 2
      years after injury. CONCLUSIONS: Patients who sustain a limb-threatening knee
      dislocation have a moderate to high level of disability 2 years after injury.
      Nearly one in five patients who present to a Level I trauma center with a
      dysvascular limb associated with a knee dislocation will require amputation.
      Prolonged warm ischemia time was associated with a high rate of amputation.
      Patients who sustain vascular injuries associated with a knee dislocation need
      immediate transport to a trauma hospital, rapid assessment and diagnosis at
      presentation, and revascularization. Patients with these injuries can be
      effectively treated without angiography before surgery.

PMID- 18090018
TI  - Exchange nailing for aseptic nonunion of femoral shaft: a retrospective cohort
      study for effect of reaming size.
AB  - BACKGROUND: Exchange nailing has been the favored method to treat aseptic
      nonunions of the femoral shaft. The recommended amount of over-reaming is at
      least 2 mm. The purpose of this study was to determine whether the effectiveness
      of nonunion treatment is greatly reduced with less than 2 mm of over-reaming.
      METHODS: Aseptic nonunions of the femoral shaft were treated by exchange nailing
      with 1 mm (n = 37) or at least 2 mm (n = 44) of over-reaming. Union rates, union
      periods, and complications were compared. Indications for exchange nailing were
      aseptic nonunions of the femoral shaft with an inserted intramedullary nail,
      shortening of less than 1.5 cm, and a fracture gap of less than 5 mm. RESULTS:
      After a mean follow-up of 3.6 years (range, 1.1-7.1 years), union rates were 31
      (91.2%) of 34 nonunions with over-reaming of 1 mm and 37 (92.5%) of 40 nonunions
      with over-reaming of 2 mm or more (p = 0.32). The mean union periods were 4.4
      months (range, 2.5-8 months) and 4.4 months (range, 3-8 months), respectively (p
      = 0.83). Except for persistent nonunions, no significant complications occurred.
      CONCLUSIONS: Exchange nailing can be considered the first choice to treat aseptic
      nonunions of the femoral shaft. The diameter of the new intramedullary nail
      should be as large as possible to reinforce the mechanical strength of the
      repair. The osteogenic potential stimulated by the reaming of cancellous bone
      graft was similar with over-reaming of 1 mm and with over-reaming of 2 mm or
      more.

PMID- 18090019
TI  - Encouraging results of treating femoral trochanteric fractures with specially
      designed double-screw nails.
AB  - BACKGROUND: Conventional intramedullary nails for trochanteric fractures have the
      disadvantages of intraoperative splintering resulting from large proximal section
      and postoperative femoral fracture caused by stress concentration at the nail
      tip. The present study reports the experience of using a specially designed
      double-screw nail with a smaller proximal section to avoid intraoperative
      splintering and a longer nail shank to avoid postoperative femoral fracture.
      METHODS: Between 2003 and 2005, 144 consecutive femoral trochanteric fractures in
      143 patients with an average age of 78.2 years were treated with double-screw
      nails. The OTA fracture classification was 31-A1 in 51 cases, 31-A2 in 65 cases,
      and 31-A3 in 28 cases. Seventy-nine patients had more than one major medical
      disease. The operation was performed using fluoroscopic guide on the fracture
      table. A distal locking screw was applied in patients with 31-A2 and A3
      fractures. At 1 year, 23 patients had died and 6 were lost to follow-up, leaving
      114 fractures for functional evaluation. RESULTS: Patients with 31-A1 fractures
      tended to have better preoperative conditions than those with 31-A2 and A3
      fractures had. The operation time and hospital stay were significantly shorter
      for those with 31-A1 fractures. Lag screw breakage occurred in four patients with
      31-A2 and A3 fractures, and two of these also had screw backout. Another three
      patients had lag screw cutout. Among these seven patients, only one with screw
      cutout underwent revision of the fixation. All 114 fractures at 12 months had
      eventual union. Preoperative mobility was recovered in 35 (85%) patients with 31
      A1 fractures and 45 (61%) with 31-A2 and A3 fractures. The functional recovery
      among patients with 31-A2 and A3 fractures was significantly worse than their
      preoperative condition and that of patients with 31-A1 fractures. CONCLUSIONS:
      The double-screw nail can yield acceptable treatment results for both 31-A1 and
      31-A2 and A3 trochanteric fractures and is particularly useful in patients with a
      small proximal femur. Type 31-A1 and 31-A2 and A3 trochanteric fractures should
      be separately analyzed in terms of treatment planning or prognostic study.

PMID- 18090020
TI  - Prevalence of pelvic fractures, associated injuries, and mortality: the United
      Kingdom perspective.
AB  - BACKGROUND: We wished to determine the characteristics of patients with pelvic
      ring fractures (PGs) in England and Wales, make comparisons to major trauma
      patients without pelvic injury (NPGs), and determine factors predicting
      mortality, including the impact of presence of pelvic reconstruction facilities
      in the receiving hospitals on outcome. METHODS: Prospective data from 106 trauma
      receiving hospitals forming the Trauma Audit and Research Network were studied.
      Between January 1989 and December 2001 data of 159,746 trauma patients were
      collected in the Trauma Audit and Research Network database. Because of
      incomplete data, 1,610 pelvic fracture patients and 13,499 patients without
      pelvic fracture were excluded from detailed analysis. In total, 11,149 patients
      in the PG and the remaining 133,486 patients in the NPG (control) group were
      included in the final analysis. RESULTS: There were statistically significantly
      more patients with an Injury Severity Score >15 in the PG group (n = 3,576;
      32.1%) than in NPG group (n = 19,238; 14.4%) (p < 0.001), indicating that pelvic
      injuries were more often associated with other injuries. The majority of patients
      sustained Abbreviated Injury Score (AIS) 2 pelvic injuries (65.0%), whereas AIS 4
      and 5 injuries were found in less than 10% of patients. Pelvic ring injuries were
      most commonly associated with chest trauma with >AIS 2 severity in 21.2% of the
      patients, head injuries (>AIS 2) in 16.9%, liver or spleen injuries in 8.0%, and
      two or more long bone fractures in 7.8%. The 3-month cumulative mortality rate of
      the patients with pelvic injuries was 14.2% (1,586 patients) versus 5.6% (7,465
      patients) of the NPG group. CONCLUSION: Age, early physiologic derangement, and
      presence of other injuries (head or trunk) were associated with reduced survival
      rates. When the expertise to deal with such a group of patients is not available,
      early transfer under safe conditions should be considered to improve survival
      rates.

PMID- 18090021
TI  - Long-term functional outcome after unstable pelvic ring fracture.
AB  - PURPOSE: In patients with unstable pelvic ring fractures, the factors related to
      poor outcome are still controversial. The purpose of our study was to evaluate
      the long-term functional outcome of patients with unstable pelvic ring fractures
      and correlate it with various other factors. METHODS: Fifty-seven patients who
      had a minimal follow-up of 2 years completed the three-view plain radiographs,
      physical examination, and functional assessment with questionnaire. There were 28
      male and 29 female patients with an average age of 42.4 years and Injury Severity
      Score of 24.6 points. The mean time of follow-up was 47.2 months. Thirty-nine
      patients were Tile type B, and 18 were type C. Twenty-three patients were treated
      conservatively, 22 with external fixation, and 12 with internal fixation. The
      results were scored with the Majeed score, the Iowa Pelvic Score, and the Medical
      Outcomes Study Short-Form 36-item Health Survey (SF-36). Statistical analysis was
      performed by use of the Pearson correlation coefficient test and multiple
      regression analysis. RESULTS: The average Majeed score was 79.7, the average IPS
      was 80.7, and the average physical component summary of the SF-36 was 13.4 points
      worse than that of the population norm. These scores correlate significantly with
      each other. The average residual displacement was 7.3 mm anteriorly and 5.2 mm
      posteriorly. Multiple regression analysis revealed that the Majeed score and the
      physical component summary of the SF-36 correlated with the presence of
      neurologic injury, and the Iowa Pelvic Score correlated with the presence of a
      mental disorder, posterior displacement, and neurologic injury. CONCLUSIONS: The
      long-term functional outcome after unstable pelvic ring fracture was not
      associated with Injury Severity Score, fracture location or fracture type. We
      discovered a close correlation between neurologic injury and functional outcome.

PMID- 18090022
TI  - Multiple-region scapular fractures had more severe chest injury than single
      region fractures: a prospective study of 107 blunt trauma patients.
AB  - BACKGROUND: We aimed to study the relationship between the number of fractured
      scapular regions, and the severity and distribution of associated injuries in
      blunt trauma patients. METHODS: One hundred seven consecutive patients with
      fractured scapulae (100 men) with a mean age of 35 (8-65) years were
      prospectively studied between January 2003 and December 2005. Mechanism of
      injury, associated injuries, Injury Severity Score (ISS), and the number of
      anatomic scapular regions involved in each fracture were studied. Patients were
      divided into single-region fracture (SRF), two-region fracture, and more than two
      region fracture groups. Computer tomography was used for fracture classification
      in 99 patients and plain radiographs were used for the remaining 8. RESULTS: Road
      traffic collisions were the most common cause of scapular fracture. Ninety-five
      patients (89%) sustained associated injuries. The most frequent was chest injury
      (68 [64%]). The median ISS was 9 (4-57) for the SRF group (n = 55), 20 (4-59) for
      the two-region fracture group (n = 30), and 22.5 (4-54) for the more than two
      region fracture group (n = 22) (p = 0.02, Kruskal-Wallis test). The median values
      of the Abbreviated Injury Scale for chest injuries for the three groups were 1 (0
      4), 3 (0-5), and 3 (0-5), respectively (p = 0.001, Kruskal-Wallis test). The SRF
      group had significantly less posterior structure injury (9 of 55) compared with
      the multiple-region fracture group (46 of 52) (p < 0.001, Fisher's exact test).
      CONCLUSIONS: Associated injuries are common in patients with scapular fractures.
      ISS and Abbreviated Injury Scale score for chest injuries are higher and
      posterior structure injuries are more frequent in patients with fractures
      involving multiple scapular regions.

PMID- 18090023
TI  - A novel clinical instrument for predicting delayed recovery after musculoskeletal
      injuries.
AB  - BACKGROUND: Early identification of patients at risk for delayed recovery after
      an injury is important to effectively target rehabilitation. This study presents
      a new instrument, the Prediction of Prolonged Self-Perceived Recovery After
      Musculoskeletal Injuries questionnaire (PPS), for prediction of self-perceived
      nonrecovery after musculoskeletal injuries. METHODS: On the basis of a historic
      cohort (model building set, n = 557), we constructed the PPS consisting of two
      demographic variables (educational level and working status), a crude injury
      classification, and patient-rated physical and mental complaints during the acute
      phase of the injury. We evaluated the PPS's ability to predict self-perceived
      nonrecovery at 6 months in a new group of patients with minor musculoskeletal
      traffic-related injuries (validation set, n = 279). RESULTS: Our findings
      demonstrate that the PPS foresees an unfavorable course with a greater accuracy
      than prediction based exclusively on information about the injury. The overall
      percentage of correct predictions in the model building set was 77%. The overall
      percentage of correct predictions in the validation set was 67%. The sensitivity
      and specificity in relation to nonrecovery at 6 months was 55% and 73%,
      respectively. CONCLUSIONS: This is the first prospective clinical study in which
      an instrument is used for prediction purpose. On the basis of our results, we
      think that the PPS, even if not fully developed, can be used by clinicians as a
      tool for early identification of patients at risk for delayed recovery after
      trauma. A nonnegligible proportion of the patients who would benefit from
      additional rehabilitation are missed by the instrument in its present form.
      Further research is needed to verify our results.

PMID- 18090024
TI  - Factors influencing discharge location after hospitalization resulting from a
      traumatic fall among older persons.
AB  - OBJECTIVE: To identify significant demographic, clinical, and nonclinical factors
      among elderly persons influencing the discharge location after hospitalization
      resulting from a traumatic fall. METHODS: Population-based case-only study with
      use of data from the 2003 National Trauma Data Bank. The study analysis included
      47,234 subjects admitted to 1 of 405 hospitals in the United States between 1989
      and 2003, and aged between 65 and 89 years. Demographic characteristics, clinical
      factors, and discharge location were obtained from the database. RESULTS: Eighty
      three percent were discharged to home, 7% to a nursing home, and 10% to a
      rehabilitation facility. Female patients and white patients were more likely
      discharged to a nursing home or a rehabilitation facility than to home. Compared
      with commercial insurance, a patients who had Medicare was more likely discharged
      to a nursing home (odds ratio = 20.9; 95% confidence interval: 18.2-23.9) or a
      rehabilitation facility (odds ratio = 5.39; 95% confidence interval: 4.86-5.96)
      than to home. A patient who was injured in the face or neck, thorax, or abdomen
      was less likely discharged to a nursing home or a rehabilitation facility than to
      home when compared with a patient injured in an upper and lower extremity. A
      patient with an injury to the spine was more likely discharged to a
      rehabilitation facility than to home when compared with a patient injured in any
      other body region. CONCLUSION: Gender, race, payment type, body region injured,
      Injury Severity Score, physiologically based Emergency Department Revised Trauma
      Score, and need for intensive care unit care were significant predictors of
      discharge location. Understanding and addressing the factors found in this study
      can improve the discharge planning process and posttreatment management.

PMID- 18090025
TI  - Base deficit-based predictive modeling of outcome in trauma patients admitted to
      intensive care units in Dutch trauma centers.
AB  - BACKGROUND: Worldwide, the base deficit is available as an objective indicator of
      acid base status. We used the base deficit as a measure of physiologic
      derangement in a Trauma and Injury Severity Score (TRISS)-like model as a
      predictor for outcome in trauma patients. METHODS: We prospectively recorded data
      of 349 consecutive trauma patients admitted to the intensive care unit and
      calculated Revised Trauma Score, Injury Severity Score and Abbreviated Injury
      Scale, and TRISS and correlated them with the simultaneously determined base
      deficit value. The delta base deficit is introduced, which is the absolute
      difference of the base deficit from its normal range (-2 to 2). A statistical
      model analogous to the TRISS model was designed in which the physiologic
      disturbance reflected by the Revised Trauma Score was replaced by the delta base
      deficit [Base Excess Injury Severity Scale (BISS) model]. Calculating the area
      under the curve (AUC) of the respective receiver operating characteristic curve
      compared these two models. Finally, the BISS model was validated in a patient
      group from another tertiary referral hospital in which similar data were recorded
      prospectively. RESULTS: We demonstrated a significant correlation between the
      delta base deficit and the calculated trauma scoring systems. Moreover, the delta
      base deficit is significantly correlated with mortality. The BISS performed
      better than the TRISS did when evaluated by the AUC of the receiver operating
      characteristic curves (AUC 0.806 vs. 0.803, respectively). Validation in an
      independent prospectively compiled dataset from another referral center showed
      comparable and even better results (AUC 0.891 vs. 0.885, respectively).
      CONCLUSIONS: The performance of our proposed BISS model was superior to that of
      the TRISS model in the populations under investigation. Nevertheless, given the
      ease of assessment and the objective value of the base deficit, it may be
      considered as a good method to predict outcome and evaluate care of trauma
      patients. Whether this can be translated to trauma patients in general needs
      further investigation.

PMID- 18090026
TI  - Effect of emergency medical technician certification for all prehospital
      personnel in a Latin American city.
AB  - BACKGROUND: In Mexico and most other Latin American countries, many emergency
      medical services (EMS) systems rely on employees and volunteers with only on-the
      job training and without formal Emergency Medical Technician (EMT) certification.
      This study sought to evaluate the costs and effectiveness of providing EMT
      certification to all personnel working in an EMS service in a Mexican city.
      METHODS: At baseline, only 20% of the prehospital personnel (medics) working for
      the EMS service in Santa Catarina, Nuevo Leon, Mexico had EMT certification.
      During a 14-month period, all such medics obtained EMT certification. The process
      and outcome of trauma care were assessed before and after this training. RESULTS:
      Mortality among persons treated by this EMS service decreased from 1.8% Before to
      0.5% after the training. The injury severity, as reflected by the prehospital
      index (PHI), was different between the two periods. Hence, adjustment for PHI by
      logistic regression was performed. The PHI- adjusted odds ratio for death in the
      after period was 0.55 compared with the before period, representing a 45%
      reduction in risk of death after EMT training. CONCLUSIONS: These data support
      the promotion of policies that require and enable EMT certification for all
      prehospital care providers in Mexico and potentially also in other Latin American
      and other middle-income developing countries.

PMID- 18090027
TI  - Amputation in military trauma surgery.
AB  - BACKGROUND: Major limb amputations are among the most debilitating wounds
      sustained by those who survive a combat injury and these injuries leave a lasting
      impression with the public. This article will review the history of major limb
      amputation in military trauma surgery. METHODS: Review of published historic and
      modern battle casualty information was undertaken in the collections of the
      medical library of the National Naval Medical Center and the National Library of
      Medicine, both in Bethesda, Maryland, and the University of Maryland Health
      Sciences Center in Baltimore, Maryland. RESULTS: The potential utility of major
      limb amputation as a life-saving surgical intervention for compound fractures and
      other devastating limb injuries has been recognized through much of written human
      history. However, the advent of gunpowder onto the battlefields of Europe in the
      14th century forced surgeons to solve the problems of, first, hemorrhage and
      then, as casualties survived the initial surgery, sepsis for amputation to
      actually improve outcomes. In the latter half of the 20th century, rapid
      evacuation from the battlefield and successful neurovascular repair has reduced
      the need for major limb amputations essentially for those required by
      insurmountable tissue loss. CONCLUSIONS: Major limb amputation remains a fearsome
      outcome of limb injury. However, during the last 500 years, military trauma
      surgeons have solved the problems of bleeding, infection, and neurovascular
      repair after major limb injury such that amputation rates even during times of
      active military conflict are at historic lows.

PMID- 18090028
TI  - V. Guidelines for sedation and analgesia during mechanical ventilation general
      overview.

PMID- 18090029
TI  - Displaced comminuted midshaft clavicle fractures: use of Mennen plate fixation
      system.
AB  - BACKGROUND: Surgical treatment of displaced comminuted midclavicular fractures
      includes open reduction and stabilization with wires, pins, or screwed plates.
      However, it is often difficult stabilizing small fragments, and there are several
      complications. The aim of this study was to assess an alternative technique using
      a Mennen plate. METHODS: From 1999 to 2004, we treated a cohort of 43 patients
      with a displaced three- or four-part midclavicular fracture. All patients were
      followed up at an average of 1 year after the injury: they had a functional
      evaluation and were assessed radiographically. RESULTS: The fractures of 41
      patients had healed, with two cases of nonunion and no case of infection or
      osteomyelitis. All of them presented normal function of the shoulder and shoulder
      girdle symmetry. CONCLUSIONS: A Mennen plate is a good device for the treatment
      of displaced midshaft clavicle fractures. The technique is simple and the
      operation time is shortened; the bone architecture is protected by any damage
      caused by drill holes; and the endosteal blood supply is preserved as a result of
      the paraskeletal position of the plate.

PMID- 18090030
TI  - Trauma intubations: can a protocol-driven approach be successful?
AB  - OBJECTIVE: To determine the success rate of a trauma airway protocol. METHODS:
      This was a prospective cohort study of trauma patients requiring intubation
      conducted for 24 months. The study facility is a Level I trauma center serving an
      urban population. The protocol suggests that the first two attempts at intubation
      be by the third-year emergency medicine resident, a hospital-wide stat overhead
      page for anesthesia occurs, which results in anesthesia (occasionally a resident
      only, but usually an attending) presence in the trauma room in 5 to 10 minutes.
      After each intubation, the emergency medicine resident or the attending physician
      completed a data collection form indicating the number of intubation attempts and
      result of each one, who performed each attempt, complications related to each
      attempt, and airway adjuncts used. RESULTS: Two hundred seventy-four patients
      were intubated during the study period by either emergency medicine physician or
      anesthesiologist with a success rate of 91.6% after the third attempt. The
      complication and cricothyrotomy rates were 9.8% and 2.6%, respectively.
      CONCLUSION: Our trauma airway protocol allows for the safe and effective
      management of the trauma airway.

PMID- 18090031
TI  - Air in "extra-dural space" after hyperbaric oxygen therapy.

PMID- 18090032
TI  - Re: Predictive value of sputum gram stain for the determination of appropriate
      antibiotic therapy in ventilator-associated pneumonia.

PMID- 18090034
TI  - Associations between mammographic density and body composition in Hispanic and
      non-Hispanic white women by menopause status.
AB  - OBJECTIVE: To evaluate the associations of body composition, including percentage
      of lean and fat mass, with the percentage of mammographic density and
      mammographic dense area among pre- and postmenopausal Hispanic and non-Hispanic
      white women. DESIGN: In this cross-sectional study, a total of 238 women aged 41
      to 50 or 56 to 70 years were recruited from local mammography clinics and
      community health centers. Postmenopausal status was defined as an absence of any
      menstrual cycle within the past 12 calendar months or having a follicle
      stimulating hormone level between 22 and 138 mIU/mL. The participants' most
      recent mammograms were used for the mammographic density analysis. Body
      composition was measured by dual-energy x-ray absorptiometry. The associations
      between the percentage of mammographic density or mammographic dense area and
      body composition components were analyzed using logistic regression. RESULTS:
      Mammographic dense areas were similar in Hispanic and non-Hispanic white women.
      The percentage of mammographic density varied by ethnicity in premenopausal (P =
      0.023), but not in postmenopausal women. Body composition, both higher lean mass
      and lower fat mass, was associated with a higher percentage of mammographic
      density (P < 0.05). Interestingly, a higher percentage of total body fat mass and
      a lower percentage of total body lean mass were correlated with larger breast
      dense areas in premenopausal women but with lower breast dense areas in
      postmenopausal women. These relationships between body composition and
      mammographic density measurements were not significantly affected by factors such
      as age, ethnicity, and body weight. CONCLUSIONS: Body composition is highly
      correlated with mammographic density and should be examined as a possible
      confounding factor in studies involving mammographic density measurements and
      breast cancer risk.

PMID- 18090035
TI  - Effect of human placental extract on menopausal symptoms, fatigue, and risk
      factors for cardiovascular disease in middle-aged Korean women.
AB  - OBJECTIVE: In Korea, human placental extract (HPE) has recently been used to
      treat various diseases (chronic liver diseases, menopause syndrome, chronic
      fatigue, skin pigment diseases, etc.), but evidence-based studies are not yet
      sufficient. The aim of this study was to examine the effects of HPE on menopausal
      symptoms, fatigue, and risk factors for cardiovascular disease in middle-aged
      Korean women in a randomized controlled trial. DESIGN: Korean women, aged 40 to
      64 years, with menopausal symptoms and fatigue were recruited as participants.
      The women were randomly assigned to a placebo group or an HPE group. The HPE
      group received subcutaneous injections of HPE in the abdomen for 8 weeks, whereas
      the placebo group received normal saline. Then, the Menopause Rating Scale, and
      Fatigue Severity Scale, and Visual Analog Scale were administered, and risk
      factors for cardiovascular disease were assessed. RESULTS: The Menopause Rating
      Scale total baseline score was not different between the two groups; however, the
      score of the HPE group decreased significantly at 8 weeks compared with that of
      the placebo group (P = 0.033). Fatigue Severity Scale and Visual Analog Scale
      scores of the placebo group did not change, whereas the scores of the HPE group
      decreased significantly during the study period (Fatigue Severity Scale, P =
      0.002; Visual Analog Scale, P = 0.001). The baseline 17beta-estradiol level was
      not significantly different between the two groups, but the 17beta-estradiol
      level of the HPE group was significantly increased at 8 weeks compared with that
      of the placebo group (P = 0.031). No changes in risk factors for cardiovascular
      disease were observed in either group. CONCLUSIONS: Menopausal symptoms and
      fatigue in middle-aged Korean women improved after 8 weeks of HPE treatment,
      whereas risk factors for cardiovascular disease did not change during the study
      period.

PMID- 18090036
TI  - Risk perception in women: a focus on menopause.
AB  - OBJECTIVE: To investigate risk perceptions in relation to menopausal experiences,
      comparing premenopausal women's expectations to actual experiences of menopause,
      including perceptions of symptoms, fears, risks of future illnesses, and side
      effects of symptomatic treatments. DESIGN: This was a cohort study using surveys
      in a random sample of Australians participating in an Australian Health Report
      series, supported by Pfizer. This article focuses on perceptions about menopause
      of 710 women. RESULTS: Peri- and postmenopausal women experienced more fatigue,
      sleeplessness, fluid retention, and bloating than premenopausal women expected to
      experience. Perimenopausal and postmenopausal women rated menopause as the "first
      day of the rest of [my] life" significantly more than premenopausal women. All
      women perceived that menopause had an impact on aging and weight gain, but more
      premenopausal women feared loss of sexuality (55%), loss of femininity (39%), and
      the inability to have more children (37%). Perceptions of illnesses differed from
      actual incidence, with 27% of all women perceiving breast cancer and 11%
      perceiving heart disease as a health risk, compared with actual female mortality
      figures of 3% and 41%, respectively. Perceptions of the effects of hormone
      therapy were inaccurate, with 53% of all women expecting a reduction in hot
      flushes, 44% expecting that hormone therapy increased breast cancer, and 23%
      expecting that hormone therapy decreased fractures. CONCLUSIONS: This study
      suggests a difference between perceptions of symptoms, fears, risks of future
      illnesses, and side effects of symptomatic treatments at menopause and actual
      experience. Because risk perception influences health-related behaviors, visits
      to healthcare providers, and treatment decisions and can be modified through
      education, an understanding of risk perception is clinically important. Further
      research is needed.

PMID- 18090037
TI  - Use of complementary and alternative medicine during the menopause transition:
      longitudinal results from the Study of Women's Health Across the Nation.
AB  - OBJECTIVE: This study examined whether use of complementary and alternative (CAM)
      therapies during the menopause transition varied by ethnicity. DESIGN: The Study
      of Women's Health Across the Nation is a prospective cohort study following a
      group of 3,302 women from five racial/ethnic groups at seven clinical sites
      nationwide. Using longitudinal data encompassing 6 years of follow-up, we
      examined trends in use of five categories of CAM (nutritional, physical,
      psychological, herbal, and folk) by menopause status and ethnicity. To account
      for potential secular trends in CAM use or availability, we also evaluated the
      trends in CAM use over calendar time. RESULTS: Approximately 80% of all
      participants had used some form of CAM at some time during the 6-year study
      period. White and Japanese women had the highest rates of use (60%), followed by
      Chinese (46%), African American (40%), and Hispanic (20%) women. Overall use of
      CAM therapy remained relatively stable over the study period. In general, CAM use
      did not seem to be strongly associated with change in menopause transition
      status. Use of CAM among white women did not change with transition status. Among
      Chinese and African American participants, we observed an increase in CAM use as
      women transitioned to perimenopause and a decrease in use of CAM with transition
      to postmenopause. Among Hispanic and Japanese women, we observed a decrease in
      use of CAM in early perimenopause, followed by an increase as women entered late
      perimenopause and a decrease as they progressed to postmenopause. Patterns of use
      for the five individual types of CAM varied. White women had relatively stable
      use of all CAM therapies through the transition. Japanese women decreased use of
      nutritional and psychological remedies and increased use of physical remedies as
      they transitioned into late perimenopause. Among African American women, use of
      psychological remedies increased as they progressed through menopause.
      CONCLUSIONS: Although CAM use did vary in some ethnic groups in relation to
      advancing menopause status, there was no evidence of influence of calendar time
      on CAM use. Patterns of CAM use during menopause are likely to be driven by
      personal experience, menopausal health, and access to therapies. Women's personal
      preferences should be taken into consideration by healthcare providers for
      medical decision making during menopause and throughout the aging process.

PMID- 18090038
TI  - HIV-associated cryptococcal meningitis.

PMID- 18090039
TI  - Difficulties in eliciting broadly neutralizing anti-HIV antibodies are not
      explained by cardiolipin autoreactivity.
AB  - OBJECTIVE: In a recent report [Haynes et al. Science 2005; 308:1906-1908],
      difficulties in eliciting broadly neutralizing antibodies to HIV were linked to
      the binding of prototypic broadly neutralizing monoclonal antibodies to
      autoantigens and in particular, to the binding of two antigp41 antibodies, 2F5
      and 4E10, to the autoantigen cardiolipin. We used a number of assays to
      understand whether 2F5 and 4E10 are autoreactive, polyreactive, or have a
      generalized affinity for lipids that may facilitate recognition of their membrane
      proximal epitopes. METHODS: 2F5 and 4E10 were evaluated for autoreactivity using
      diagnostic assays developed to detect serum antibodies associated with
      antiphospholipid syndrome (APS). As an indication of polyreactivity, we measured
      the binding of 2F5 and 4E10 to liposomal bilayers of differing composition using
      surface plasmon resonance (SPR) spectroscopy and to protein microarrays using
      biochip technology. RESULTS: 2F5 showed completely negative results in the APS
      and SPR studies, indicating that it is neither autoreactive nor absolutely
      requires phospholipid binding for epitope recognition. In contrast, 4E10 bound to
      more than one lipid and showed weak activity in the APS studies. The activity
      displayed by 4E10 more closely resembles that of antiphospholipid antibodies
      elicited during many infections than that of autoimmune APS antibodies, at
      variance with the notion that difficulites in eliciting 4E10-like antibodies can
      be attributed to tolerance mechanisms. The microarray studies further indicated
      that broadly neutralizing anti-HIV mAb are not exceptionally polyreactive.
      CONCLUSION: These results suggest that autoantigen mimicry cannot be reliably
      invoked as a general mechanism for HIV immune evasion.

PMID- 18090040
TI  - Aberrant Epstein-Barr virus persistence in HIV carriers is characterized by anti
      Epstein-Barr virus IgA and high cellular viral loads with restricted
      transcription.
AB  - OBJECTIVE: Epstein-Barr virus (EBV)-positive lymphomas in HIV carriers are
      paralleled by elevated EBV-DNA loads in the circulation. Approximately 20% of
      asymptomatic HIV carriers also show elevated circulating EBV-DNA loads. We aimed
      to characterize the nature of this EBV DNA and to determine the transcriptional
      phenotype of EBV in blood, in relation to serological parameters. DESIGN: A total
      of 197 random asymptomatic HIV carriers, representing 2% of the Dutch HIV
      positive population, were sampled for blood, peripheral blood mononuclear cells
      and plasma. In addition, 39 EBV-DNA carriers were sampled twice, with a 5-year
      interval. METHODS: EBV-DNA loads were determined by LightCycler-based real-time
      polymerase chain reaction (PCR). EBV transcription was studied by nucleic acid
      sequence-based amplification and reverse transcriptase PCR. IgA and IgG
      antibodies to EBV antigens EBNA1 and VCA-p18 were quantified by synthetic peptide
      based enzyme-linked immunosorbent assay. RESULTS: : Elevated EBV-DNA loads were
      found in whole blood of 19.3% of the tested HIV population, which were persistent
      in 82%. Plasma samples were EBV-DNA negative and circulating EBV DNA could be
      attributed to the B-cell compartment. Transcription of only LMP2 and (non
      translated) transcripts from the BamHI-A region of the EBV genome was found,
      whereas EBNA1, LMP1 and lytic EBV transcripts were absent despite high cellular
      EBV-DNA loads. IgA-reactivity to VCA-p18 was seen in 69%. IgG to VCA-p18 was
      significantly higher in high EBV-DNA load carriers. CONCLUSION: Asymptomatic HIV
      carriers show aberrant EBV persistence in the circulation, characterized by
      elevated, B-cell-associated EBV-DNA loads. EBV transcription is restricted,
      arguing for EBV gene shutdown in circulating EBV-carrying B cells. Increased IgA
      and IgG reactive to VCA-p18 is indicative of increased lytic EBV replication,
      possibly occurring at mucosal lymphoid sites but not in the circulation.

PMID- 18090041
TI  - Cognitive dysfunction in HIV encephalitic SCID mice correlates with levels of
      Interferon-alpha in the brain.
AB  - BACKGROUND: Interferon alpha (IFNalpha) is an antiviral cytokine produced in
      response to viral infection. IFNalpha also acts as a neuromodulatory molecule in
      the central nervous system (CNS). Elevated IFNalpha in the CNS causes cognitive
      deficits. OBJECTIVE: To determine if elevated levels of IFNalpha in an HIV
      encephalitis mouse model correlate with cognitive deficits. METHODS: C57BL/6J
      SCID mice were inoculated intracerebrally (i.c.) with HIV infected or uninfected
      (control) macrophages and cognitively tested in a water escape radial arm maze.
      After behavioral testing was completed, immunohistochemistry and ELISA were used
      to examine brain pathology and IFNalpha expression. RESULTS: Mice injected i.c.
      with HIV infected macrophages exhibited significantly more working memory errors,
      particularly in trials with the highest memory load. Immunohistochemistry
      indicated increased mouse IFNalpha staining prevalent on neurons and glial cells
      in the brains of mice with HIV infected macrophages compared to mice with
      uninfected control macrophages. In addition, IFNalpha levels in the brain
      correlated directly with working memory errors for mice with HIV infected
      macrophages. CONCLUSIONS: These data suggest that the cognitive deficit noted for
      the C57BL/6J SCID mice with HIV infected macrophages is mediated by the infection
      induced increase in IFNalpha.

PMID- 18090042
TI  - Reassessment of autoreactivity of the broadly neutralizing HIV antibodies 4E10
      and 2F5 and retrospective analysis of clinical safety data.
AB  - BACKGROUND: The broadly neutralizing recombinant human HIV-1 antibodies 4E10, 2F5
      and Igh1b12 are reported to have autoreactive potential, which is significant for
      HIV-1 vaccine development and passive immunotherapy using these antibodies.
      OBJECTIVE: To investigate the clinical relevance of these findings in subjects
      receiving passive immunotherapy with these antibodies. METHODS: Four types of
      investigations were performed: (1) Investigation of clotting parameters in an
      ongoing clinical study with 4E10, 2F5 and 2G12. (2) Mixing experiments of pooled
      plasma with the same antibodies. (3) Retrospective analysis of serum from
      patients who received passive immunotherapy with 4E10, 2F5 and 2G12 either alone
      or in combination. (4) Assessment of clinical safety data obtained after 418
      infusions with these antibodies. RESULTS: Standard clinical assays confirmed that
      4E10 showed low-level cross-reactivity with cardiolipin, while previously
      reported cardiolipin cross-reactivity for 2F5 could not be confirmed. High serum
      titers of 4E10 induced mild prolongation of the activated partial thromboplastin
      time, which resolved with the wash out of 4E10. Neither 2F5 nor 2G12 affected
      coagulation. Repeated high-dose infusions of the monoclonal antibody combination
      were well tolerated with no incidence for thrombotic complications after 418
      infusions in 39 subjects. CONCLUSIONS: Monoclonal antibody 4E10 but not 2F5 or
      2G12 showed autoreactive binding specificities. Infusion of 4E10 resulted in
      transient low anticardiolipin titers. Although an increased thromboembolic risk
      cannot definitely be excluded, this risk appears to be low and likely depend on
      underlying disorders.

PMID- 18090043
TI  - Analysis of occult hepatitis B virus infection in liver tissue of HIV patients
      with chronic hepatitis C.
AB  - OBJECTIVE: Current data on the prevalence of occult hepatitis B virus (HBV)
      infection in HIV-positive individuals conflict. As occult HBV infection could
      have an impact on the outcome of liver disease in HIV-positive patients, we
      investigated a large number of HIV-positive/HBV-surface-antigen (HBsAg) negative
      subjects with hepatitis C virus (HCV) infection by using the 'gold standard'
      approach for occult HBV detection--analysis of liver DNA extracts. METHODS: The
      presence or absence of HBV DNA was determined by PCR testing of four different
      viral genomic regions in DNA extracts of needle liver biopsy specimens of 101
      HBsAg negative individuals with HIV/HCV co-infection. HBV genotyping was
      performed by sequencing analysis of the preS-S gene in occult HBV isolates from
      18 cases. RESULTS: Occult HBV infection was diagnosed in 42 of the 101 cases
      (41%). No clinically relevant difference was found between occult HBV-positive
      and -negative patients. HBV genotype D and A were detected, respectively, in 11
      (61%) and 7 (39%) of 18 cases analysed. CONCLUSIONS: Occult HBV infection
      frequently occurs in HIV/HCV co-infected patients indicating the importance of
      performing prospective studies able to clarify its clinical impact in these
      patients. HBV genotype A is highly prevalent in HIV-infected subjects with occult
      HBV infection in a similar way to HBsAg/HIV-positive individuals.

PMID- 18090044
TI  - Depletion of natural killer cells in the colonic lamina propria of viraemic HIV-1
      infected individuals.
AB  - BACKGROUND: HIV-1 infection is known to have a detrimental impact on peripheral
      blood natural killer cell phenotype and function. Chronic HIV-1 also causes a
      substantial depletion of CD4+ T cells in the gastrointestinal tract and the
      blood. OBJECTIVE: To investigate the impact of chronic HIV-1 infection with on
      natural killer cell populations in the gastrointestinal tract and the effect of
      suppression of plasma viraemia with antiretroviral therapy. METHODS: Lymphocyte
      populations were extracted from the lamina propria of biopsies taken from the
      sigmoid colon of HIV-1-infected and uninfected individuals. The proportions of
      natural killer cell subsets were compared in viraemic (n = 15) and aviraemic HIV
      1-positive, HAART-treated individuals (n = 27) and HIV-1 negative control
      individuals (n = 26) using flow cytometry on gated subsets. RESULTS: Natural
      killer cells are depleted in colonic biopsies from HIV-1-infected individuals
      with detectable plasma virus in comparison with HIV-1-negative individuals. A
      significant increase in the proportion of both natural killer and CD4+ T cells in
      the colonic lamina propria is observed in aviraemic individuals compared to
      viraemic individuals. CONCLUSIONS: Chronic HIV-1 infection results in depletion
      of both natural killer cells and CD4+ T cells in colonic tissue and
      antiretroviral therapy results in a recovery of these subsets in individuals with
      undetectable plasma viral load.

PMID- 18090045
TI  - Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers.
AB  - BACKGROUND: Some HIV protease inhibitors (PIs) have been shown to induce insulin
      resistance in vitro but the degree to which specific PIs affect insulin
      sensitivity in humans is less well understood. METHODS: In two separate double
      blind, randomized, cross-over studies, we assessed the effects of a single dose
      of ritonavir (800 mg) and amprenavir (1200 mg) on insulin sensitivity (euglycemic
      hyperglycemic clamp) in healthy normal volunteers. RESULTS: Ritonavir decreased
      insulin sensitivity (-15%; P = 0.008 versus placebo) and non-oxidative glucose
      disposal (-30%; P = 0.0004), whereas neither were affected by amprenavir
      administration. CONCLUSION: Compared to previously performed studies of identical
      design using single doses of indinavir and lopinavir/ritonavir, a hierarchy of
      insulin resistance was observed with the greatest effect seen with indinavir
      followed by ritonavir and lopinavir/ritonavir, with little effect of amprenavir.

PMID- 18090046
TI  - CYP2B6 genetic variants are associated with nevirapine pharmacokinetics and
      clinical response in HIV-1-infected children.
AB  - BACKGROUND: Cytochrome P450 2B6 (CYP2B6)-G516T genotype is associated with
      altered activity of hepatic CYP2B6 and efavirenz pharmacokinetics, but the
      relationship between the CYP2B6-G516T genotype and nevirapine (NVP)
      pharmacokinetics in plasma and cerebrospinal fluid (CSF) is limited. METHODS: In
      126 children who received NVP and protease inhibitors from PACTG 366 and 377
      cohorts, CYP2B6 and ATP-binding cassette, sub-family B, member 1 (ABCB1) gene
      polymorphisms were analyzed using real-time PCR. Plasma NVP pharmacokinetics and
      clinical data were collected and levels of NVP in CSF were evaluated in children
      with HIV-related neurologic diseases. RESULTS: NVP oral clearance in children
      with the CYP2B6-516-T/T genotype (homozygous variant, n = 14) was 1.6 l/h per m2,
      which was significantly decreased compared to 2.3 l/h per m2 in those with the 
      G/G (wild type, n = 49, P = 0.002) and 2.1 l/h per m2 in those with the -G/T
      genotype (heterozygous variants, n = 63, P = 0.008). Furthermore, children with
      the -T/T genotype had a significant increase in CD4+ T-cell percentage (+9.0%)
      compared with those with the -G/G (+3.2%, P = 0.01) and -G/T genotype (+5.0%, P =
      0.04) from baseline to week 12. The same trend continued at week 24. Although
      ABCB1-C3435T genotypes did not affect plasma NVP pharmacokinetics (P = 0.39), the
      NVP CSF: plasma ratios were significantly higher in children with the ABCB1-3435
      C/T or -T/T genotypes (0.62, n = 9) in comparison with those with the ABCB1-3435
      C/C genotype (0.43, n = 5) (P = 0.01). CONCLUSIONS: The CYP2B6-G516T genotype
      alters NVP pharmacokinetics and the immunologic response to NVP-containing HAART
      regimens in children. These data suggest that the CYP2B6-G516T is an important
      genetic variant that alters the pharmacokinetics and response to HAART regimens
      containing NVP.

PMID- 18090047
TI  - Predictors of optimal viral suppression in patients switched to abacavir,
      lamivudine, and zidovudine: the Swiss HIV Cohort Study.
AB  - OBJECTIVE: To investigate predictors of continued HIV RNA viral load suppression
      in individuals switched to abacavir (ABC), lamivudine (3TC) and zidovudine (ZDV)
      after successful previous treatment with a protease inhibitor or non-nucleoside
      reverse transcriptase inhibitor-based combination antiretroviral therapy. DESIGN
      AND METHODS: An observational cohort study, which included individuals in the
      Swiss HIV Cohort Study switching to ABC/3TC/ZDV following successful suppression
      of viral load. The primary endpoint was time to treatment failure defined as the
      first of the following events: two consecutiveviral load measurements > 400
      copies/ml under ABC/3TC/ZDV, one viral load measurement > 400 copies/ml and
      subsequent discontinuation of ABC/3TC/ZDV within 3 months, AIDS or death.
      RESULTS: We included 495 individuals; 47 experienced treatment failure in 1459
      person-years of follow-up [rate = 3.22 events/100 person-years; 95% confidence
      interval (95% CI), 2.30-4.14]. Of all failures, 62% occurred in the first year
      after switching to ABC/3TC/ZDV. In a Cox regression analysis, treatment failure
      was independently associated with earlier exposure to nucleoside reverse
      transcriptase inhibitor (NRTI) mono or dual therapy [hazard ratio (HR), 8.02; 95%
      CI, 4.19-15.35) and low CD4 cell count at the time of the switch (HR, 0.66; 95%
      CI, 0.51-0.87 by +100 cells/microl up to 500 cells/microl). In patients without
      earlier exposure to mono or dual therapy, AIDS prior to switch to simplified
      maintenance therapy was an additional risk factor. CONCLUSIONS: The failure rate
      was low in patients with suppressed viral load and switch to ABC/3TC/ZDV
      treatment. Patients with earlier exposure to mono or dual NRTI therapy, low CD4
      cell count at time of switch, or AIDS are at increased risk of treatment failure,
      limiting the use of ABC/3TC/ZDV in these patient groups.

PMID- 18090048
TI  - Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults.
AB  - OBJECTIVES: To define the incidence of fibrosis progression among hepatitis C
      virus (HCV)/HIV-co-infected adults, to assess whether HCV or HIV treatment alters
      the risk of progression, and to determine the utility of liver biopsy to predict
      future disease. DESIGN: This prospective cohort evaluated 184 HIV/HCV-co-infected
      individuals who had at least two liver biopsies (median interval 2.9 years).
      METHODS: Biopsies were scored according to the Ishak modified histological
      activity index scoring system by a single pathologist blind to biopsy sequence.
      Significant fibrosis progression was defined as an increase of at least two Ishak
      fibrosis units between the first and second liver biopsy. Logistic regression
      analysis was used to assess determinants of fibrosis progression. RESULTS: A
      total of 174 non-cirrhotic patients were eligible; the majority were African
      American men undergoing HIV treatment. On initial biopsy, no or minimal fibrosis
      was identified in 136 patients (77%). Significant fibrosis progression occurred
      in 41 patients (24%). Measures of HIV disease and its treatment before and after
      initial biopsy were not significantly different in progressors and non
      progressors. Fibrosis progression was not associated with HCV treatment, which
      was received by 37 patients (21%) but only three sustained HCV-RNA suppression.
      In adjusted analysis, only an elevated serum aspartate aminotransferase level
      between biopsies was associated with progression (odd ratio 3.4, 95% confidence
      interval 1.4-7.9). CONCLUSION: Over a 3-year interval, significant fibrosis
      progression can occur in co-infected individuals even if minimal disease was
      detected on initial biopsy. In this context, factors other than treatment for HIV
      or HCV modify the risk of fibrosis progression.

PMID- 18090050
TI  - Transmission of HIV-1 drug resistance in Switzerland: a 10-year molecular
      epidemiology survey.
AB  - OBJECTIVES: Representative prevalence data of transmitted drug-resistant HIV-1
      are essential to establish accurate guidelines addressing resistance testing and
      first-line treatments. METHODS: Systematic resistance testing was carried out in
      individuals in Switzerland with documented HIV-1 seroconversion during 1996-2005
      and available samples with RNA > 1000 copies/ml obtained within 1 year of
      estimated seroconversion. Resistance interpretation used the Stanford list of
      mutations for surveillance of transmitted drug resistance and the French National
      Agency for AIDS Research algorithm. RESULTS: Viral sequences from 822 individuals
      were available. Risk groups were men having sex with men (42%), heterosexual
      contacts (32%) and intravenous drug users (20%); 30% were infected with non-B
      subtype viruses. Overall, prevalence of transmitted resistance was 7.7% [95%
      confidence interval (CI), 5.9-9.5] for any drug, 5.5% (95% CI, 3.9-7.1) for
      nucleoside reverse transcriptase inhibitors, 1.9% (95% CI, 1.0-2.8) for non
      nucleoside reverse transcriptase inhibitors and 2.7% (95% CI, 1.6-3.8) for
      protease inhibitors. Dual- or triple-class resistance was observed in 2% (95% CI,
      0.8-2.5). No significant trend in prevalence of transmitted resistance was
      observed over years. There were no differences according to ethnicity, risk
      groups or gender, but prevalence of transmitted resistance was highest among
      individuals infected with subtype B virus. CONCLUSIONS: The transmission rate of
      drug-resistant HIV-1 has been stable since 1996, with very rare transmission of
      dual- or triple-class resistance. These data suggest that transmission of drug
      resistance in the setting of easy access to antiretroviral treatment can remain
      stable and be kept at a low level.

PMID- 18090049
TI  - Effect of twice-daily nevirapine on adherence in HIV-1-infected patients: a
      randomized controlled study.
AB  - OBJECTIVE: For optimal adherence, once-daily dosing is best. Whether this applies
      to antiretroviral therapy is unknown. We thus aimed to determine the effect of
      once-daily dosing on adherence to nevirapine. DESIGN: A three-phase (3-month
      observational, 4-month randomized, 5-month interventional) open-label, clinical
      trial at four French academic medical centres during 2005-2006 among 62
      chronically HIV-1-infected subjects with long-lasting viral suppression under a
      twice-a-day nevirapine-based antiretroviral combination. METHODS: Adherence was
      measured using electronic monitoring devices and validated by sequential plasma
      drug levels. Participants were randomly assigned to switch to nevirapine 400 mg
      once-daily (n = 31) or continue nevirapine 200 mg twice-a-day (n = 31). After the
      randomized phase, participants had an opportunity to choose their antiretroviral
      dosage. Primary outcome was the mean percentage of adherence. RESULTS: Fifty-two
      patients qualified for electronic data analysis. During the randomized phase, the
      mean adherence rate was non-significantly superior by 0.5% in once-daily versus
      twice-a-day dosing (P = 0.68), adjusting for previous twice-a-day adherence rate
      (P < 0.0001). Once-daily group increased days without dose [odds ratio (OR) 1.7;
      95% confidence interval (CI) 1.0, 2.8; P = 0.04], adjusting for previous drug
      interruptions (P < 0.0001). In the longitudinal analysis, once-daily dosing was
      significantly associated with at least two consecutive days without dose (OR 4.4;
      95% CI 1.9, 10.3; P < 0.001). CONCLUSION: Changing from twice to once-daily
      nevirapine does not improve adherence. Supporting continuous adherence to
      antiretroviral therapy in the 'once-a-day era' remains a challenge, even if more
      potent regimens can achieve viral suppression at lower adherence levels.

PMID- 18090051
TI  - Risk of HIV infection but not other sexually transmitted diseases is lower among
      homeless Muslim men in Kolkata.
AB  - OBJECTIVE: To compare the risk of HIV and sexually transmitted diseases (STD)
      among homeless Muslim (circumcised) and Hindu (uncircumcised) men in Kolkata,
      India. BACKGROUND: Many observational studies and clinical trials in Africa have
      demonstrated that male circumcision provides protection against HIV acquisition,
      but there are sparse data on circumcision and HIV in India, which has the largest
      number of HIV cases in the world. METHODS: Using a two-stage probability
      proportionate to size cluster design among homeless men aged 18-49 years in
      Kolkata, India, data were obtained on religion, behavioral risk factors, and
      HIV/STD prevalence, by administering an anonymous questionnaire. Rapid HIV tests
      and testing for syphilis were performed on blood, and urine samples were obtained
      to test for gonorrhea. RESULTS: The odds ratio for HIV among Muslims
      (circumcised) compared to Hindus (uncircumcised) was 0.43 (95% confidence
      interval 0.29-0.67). Despite Muslims having more partners and visits to
      commercial sex workers, the rates of syphilis and gonorrhea were similar. The
      results suggest that a biological effect of circumcision protects against HIV
      infection. CONCLUSION: The beneficial effect of circumcision should be
      communicated to high-risk groups, as well as to the general population.

PMID- 18090052
TI  - Improved detection of acute HIV-1 infection in sub-Saharan Africa: development of
      a risk score algorithm.
AB  - OBJECTIVE: Individuals with acute (preseroconversion) HIV infection (AHI) are
      important in the spread of HIV. The identification of AHI requires the detection
      of viral proteins or nucleic acids with techniques that are often unaffordable
      for routine use. To facilitate the efficient use of these tests, we sought to
      develop a risk score algorithm for identifying likely AHI cases and targeting the
      tests towards those individuals. DESIGN: A cross-sectional study of 1448 adults
      attending a sexually transmitted infections (STI) clinic in Malawi. METHODS:
      Using logistic regression, we identified risk behaviors, symptoms, HIV rapid test
      results, and STI syndromes that were predictive of AHI. We assigned a model-based
      score to each predictor and calculated a risk score for each participant.
      RESULTS: Twenty-one participants (1.45%) had AHI, 588 had established HIV
      infection, and 839 were HIV-negative. AHI was strongly associated with discordant
      rapid HIV tests and genital ulcer disease (GUD). The algorithm also included
      diarrhea, more than one sexual partner in 2 months, body ache, and fever.
      Corresponding predictor scores were 1 for fever, body ache, and more than one
      partner; 2 for diarrhea and GUD; and 4 for discordant rapid tests. A risk score
      of 2 or greater was 95.2% sensitive and 60.5% specific in detecting AHI.
      CONCLUSION: Using this algorithm, we could identify 95% of AHI cases by
      performing nucleic acid or protein tests in only 40% of patients. Risk score
      algorithms could enable rapid, reliable AHI detection in resource-limited
      settings.

PMID- 18090053
TI  - HIV-1 X4/R5 co-receptor in viral reservoir during suppressive HAART.
AB  - As immune recovery during HAART is mainly caused by the expansion of X4-naive
      cells, we studied the evolution of HIV tropism in the reservoir of 34 patients
      receiving 48 weeks of HAART. No change in virus tropism was observed over time,
      but patients with X4 viruses had higher HIV-1 proviral DNA levels than patients
      with R5 viruses. This suggests that CCR5 antagonist activity should not be
      compromised in patients harbouring R5 viruses before starting HAART.

PMID- 18090054
TI  - Treatment response to ritonavir-boosted tipranavir versus ritonavir-boosted
      lopinavir in HIV-1 patients with higher lopinavir mutation scores.
AB  - Week 48 HIV-RNA treatment response to the protease inhibitor tipranavir co
      administered with ritonavir was compared with that of lopinavir co-administered
      with ritonavir in patients whose baseline isolates had varying lopinavir
      genotypic mutation scores. With increasing lopinavir mutation scores, the
      proportion of patients achieving a week 48 treatment response was increased in
      the tipranavir/ritonavir compared with the lopinavir/ritonavir arm.
      Tipranavir/ritonavir therapy improves treatment response rates compared with
      lopinavir/ritonavir in patients whose viruses have reduced susceptibility to
      lopinavir/ritonavir.

PMID- 18090056
TI  - Kaposi's sarcoma in HIV-infected patients: when and how should we evaluate bone
      involvement?

PMID- 18090055
TI  - Increased incidence of cutaneous mycoses after HAART initiation: a benign form of
      immune reconstitution disease?
AB  - Immune reconstitution disease (IRD) has been associated with many pathogens after
      the initiation of antiretroviral therapy for advanced HIV infection. A
      retrospective cohort study was conducted to determine whether cutaneous mycoses
      were also associated with IRD. After adjusting for various confounding factors,
      the recent initiation of HAART was found to be associated with an increased
      incidence of cutaneous mycoses when compared with untreated patients.

PMID- 18090058
TI  - Lack of anti-HIV activity of entecavir in an HIV patient coinfected with
      hepatitis B and delta viruses.

PMID- 18090057
TI  - A truvada hypersensitivity reaction simulating abacavir hypersensitivity.

PMID- 18090059
TI  - Large lymphadenopathies complicating the abacavir hypersensitivity reaction.

PMID- 18090060
TI  - Exploring sex/gender differences in women's cardiovascular health.

PMID- 18090061
TI  - The role of sex-specific results reporting in cardiovascular disease.
AB  - Cardiovascular disease (CVD) is the primary cause of death among women worldwide.
      In the United States, more women than men die of CVD every year. Research has
      shown that there are important sex differences in terms of prevention, diagnosis,
      treatment, and outcomes in patients with CVD. Although women are being included
      in clinical trials in increasing numbers, lack of knowledge about sex differences
      persists because sex-specific analysis and reporting of sex-specific results
      remains limited. This knowledge gap limits the ability of health care
      professionals to provide optimal care for both women and men. Ongoing support and
      encouragement is needed for both the inclusion of sufficient numbers of women in
      clinical trials and for the reporting of sex-specific results of CVD trials. This
      increased knowledge and awareness can then be used to optimize high quality care
      for men and women.

PMID- 18090062
TI  - Diagnostic strategies for heart disease in women: an update on imaging techniques
      for optimal management.
AB  - Significant progress has been made toward increasing awareness of the risks of
      heart disease in women and in the area of sex-specific cardiovascular research.
      Yet, coronary artery disease remains the leading cause of death of women in the
      western world. Over the last decade, the increased research focus of women at
      risk for ischemic heart disease has helped in defining and delineating some of
      the sex-specific factors, which have adversely affected the accuracy of imaging
      techniques in women. A focused body of clinical research has been published over
      the last few years, and there now exists a growing body of evidence on the
      diagnostic and prognostic accuracy of contemporary cardiovascular imaging
      techniques in women. Recent publications specifically addressing this issue
      [namely the 2005 American Heart Association Statement on Cardiac Imaging in
      Women, and the 2006 Women's Ischemia Syndrome Evaluation (WISE) study] are now
      changing the existing paradigm of ischemic heart disease from one representing a
      "man's disease," to one including sex-specific algorithms. In this article we
      review the literature regarding the diagnostic and prognostic evaluation of
      coronary artery disease in women with respect to imaging.

PMID- 18090063
TI  - Do diet, folic acid, and vitamins matter? What did we learn from the Women's
      Health Initiative, the Women's Health Study, the Women's Antioxidant and Folic
      Acid Cardiovascular Study, and other clinical trials?
AB  - Data from recent randomized clinical trials have contributed substantially to our
      understanding of appropriate interventions for coronary heart disease in women.
      Addressed in this monograph are issues of diet, folic acid, and antioxidant
      vitamins. Importantly, these randomized clinical trials have helped to clarify
      conflicting information from observational data, and to aid clinicians and their
      women patients in making appropriate choices of coronary and cardiovascular
      preventive therapy.

PMID- 18090064
TI  - Valvular heart disease: focus on women.
AB  - Calcific aortic stenosis is a disease of the elderly and aortic valve replacement
      should always be considered for severe symptomatic disease; comorbidities, not
      age, determine surgical risk. Aortic regurgitation imposes a pressure and volume
      load on the left ventricle so that close monitoring is needed to identify
      patients at risk for irreversible left ventricular dysfunction, although symptoms
      are the most common indication for valve replacement. Early intervention now is
      recommended for rheumatic mitral stenosis due to the effectiveness of
      percutaneous balloon valvotomy. Earlier intervention also may be considered in
      selected patients with mitral regurgitation at experienced centers when valve
      anatomy is favorable for a successful repair. Semiquantitative descriptors of
      regurgitation as mild, moderate, or severe are no longer adequate; management of
      adults with chronic valve disease requires quantitation of both the severity of
      valve disease and of left ventricular size and systolic function.

PMID- 18090065
TI  - Implantable cardioverter-defibrillator use and benefit in women.
AB  - Women currently receive far fewer implantable cardioverter-defibrillators (ICDs)
      than do men. Some studies suggest bias in device utilization, with fewer women
      receiving ICDs despite a similar clinical profile. Other studies, however,
      describe differences in clinical presentation and arrhythmia risk. There may be
      autonomic and electrophysiological factors that suggest a lower susceptibility to
      arrhythmia in women. Although the data on the benefits of the ICD in women are
      limited by the low numbers of women enrolled in the landmark studies, most
      studies do suggest an efficacy in women similar to that in men. Further research
      is needed on the use of ICDs in women.

PMID- 18090066
TI  - Effects of electromagnetic interference on implanted cardiac devices and their
      management.
AB  - Potential interference between implanted cardiac devices such as pacemakers and
      implantable cardioverter-defibrillators and electromagnetic fields is an
      important concern for physicians taking care of patients with pacemakers and
      implantable cardioverter-defibrillators. There are many sources of
      electromagnetic interference (EMI); however, only a small number of these cause
      significant problems that need attention. Regardless of its source, EMI is of
      greater concern for a patient who is dependent on paced rhythm because inhibition
      of the pacemaker by EMI may produce ventricular standstill. It is important that
      cardiologists, internists, emergency medicine, critical care physicians, and
      anesthesiologists be aware of how EMI can affect the function of implanted
      cardiac devices so that appropriate treatment can be rendered and preventive
      measures instituted.

PMID- 18090067
TI  - Cardiac resynchronization therapy in patients with chronic atrial fibrillation.
AB  - Heart failure (HF) and atrial fibrillation (AF), 2 of the most common
      cardiovascular disorders, often coexist in the same patient, as 1 condition can
      lead to the other. The best approach to AF management in patients with HF is
      currently under investigation, but there seems to be an abundance of evidence in
      support of cardiac resynchronization therapy (CRT) in this group of patients. In
      addition, CRT is emerging as a superior option to stand-alone right ventricular
      pacing in patients with structural heart disease. However, in patients with AF,
      an adequate rate control is critical for this therapy to be highly effective. As
      control of the ventricular response can be difficult to achieve in many of those
      patients, often a nonpharmacologic intervention is required, such as ablation of
      the atrioventricular node to create heart block. The definitive role for CRT with
      or without atrioventricular nodal ablation in patients with AF and HF is yet to
      be studied in large, well-designed, randomized, controlled clinical trials.

PMID- 18090068
TI  - Aliskiren: an oral renin inhibitor for the treatment of hypertension.
AB  - Hypertension is a common chronic disease that leads to significant cardiovascular
      morbidity and mortality worldwide. Blood pressure control is critical in reducing
      the end-organ complications, such as stroke, myocardial infarction, heart
      failure, or kidney disease. Currently available antihypertensive agents work by
      different mechanisms to reduce blood pressure. Aliskiren, a novel direct renin
      inhibitor, lowers blood pressure by decreasing renin activity, and angiotensin I
      and II levels. At the approved dosage (150-300 mg once daily), it reduces
      systolic blood pressure by 12-16 mm Hg and diastolic blood pressure by 2-12 mm
      Hg. In studies its efficacy was comparable to losartan 100 mg, irbesartan 150 mg,
      and valsartan 80-320 mg. When used adjunctively with ramipril, an angiotensin
      converting enzyme (ACE) inhibitor, valsartan, an angiotensin II receptor blocker
      (ARB), or hydrochlorothiazide, a diuretic, it provides additional blood pressure
      reduction compared with placebo or monotherapy. Aliskiren is well tolerated, with
      the most common side effects being gastrointestinal symptoms, fatigue, weakness,
      and headache. In short-term clinical trials, aliskiren caused fewer disturbances
      in potassium levels when compared with hydrochlorothiazide, ACE inhibitors and
      ARBs. Long-term data on morbidity and mortality outcomes are not currently
      available, thus it is unknown whether aliskiren would join ACE inhibitors and
      ARBs as the preferred hypertensive agents for end organ protection. At this time,
      aliskiren should be considered as an alternative agent for mild-to-moderate
      hypertension, or as an adjunctive therapy when preferred agents fail to maintain
      optimal blood pressure control. It is also an option for those patients who have
      contraindications or intolerability to other antihypertensive agents, including
      dry cough induced by ACE inhibitors.

PMID- 18090069
TI  - Transpedicular partial corpectomy without anterior vertebral reconstruction in
      thoracic spinal metastases.
AB  - STUDY DESIGN: We retrospectively reviewed surgical results of posterolateral
      transpedicular partial corpectomy without anterior vertebral reconstruction in 23
      consecutive patients with symptomatic metastatic spinal cord compression at
      thoracic spine. OBJECTIVE: To evaluate postoperative outcomes and survival rates
      of patients undergoing transpedicular partial corpectomy without anterior
      vertebral reconstruction. SUMMARY OF BACKGROUND DATA: The need for anterior
      reconstruction after radical resection of vertebral body tumors has been
      emphasized by several authors. However, the stability of thoracic spine is
      substantially increased by the rib cage. The role of reconstruction may be not
      necessary in thoracic spine when partial corpectomy is performed. METHODS: From
      November 2001 to November 2006, 23 patients with symptomatic metastatic spinal
      cord compression at thoracic spine underwent palliative surgery using a
      transpedicular partial corpectomy without anterior vertebral reconstruction. The
      indication for surgery was neurologic progression due to spinal cord compression.
      RESULTS: Patients ranged in age from 20 to 88 years (mean, 57.0 years).
      Neurologic improvement by at least one Frankel grade was noted in 19 of 23 cases
      (82.6%). Overall, 73.9% of patients (17 of 23) could walk after surgery. There
      was no intraoperative mortality. Median survival time was 11.3 months. There was
      no implant failure. CONCLUSION: The results of this study suggest that the
      stability of implants can be maintained up to 55.8 months without anterior
      vertebral reconstruction in thoracic spine.

PMID- 18090070
TI  - Effect of low-dose ketamine on voltage requirement for transcranial electrical
      motor evoked potentials in children.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVE.: To determine the effect of
      low-dose ketamine on the voltage needed to elicit maximal amplitude of the motor
      evoked response to transcranial electrical stimulation during
      propofol/remifentanil anesthesia in children undergoing scoliosis surgery.
      SUMMARY OF BACKGROUND DATA: Motor-evoked potentials (MEPs) are increasingly used
      to assess the integrity of motor pathways during surgery. Whereas most general
      anesthetics depress MEP amplitude, the effect of ketamine has been variable,
      ranging from little or no reduction to an increase in amplitude, suggesting that
      ketamine may be useful as an agent to facilitate MEP monitoring. We tested the
      hypothesis that low-dose ketamine would reduce the voltage required to elicit
      maximal amplitude of the motor-evoked response to transcranial electrical
      stimulation during propofol/remifentanil anesthesia. METHODS: Thirty-four
      patients 12 to 16 years of age undergoing posterior instrumentation for
      correction of idiopathic scoliosis were randomly assigned to receive low-dose
      ketamine (0.5 mg/kg bolus, followed by 4 microg/kg/min infusion) or an equal
      volume of saline. Anesthesia was maintained using a mixture of 30% oxygen in air,
      continuous infusion of propofol at a rate of 100 to 150 microg/kg per min, and
      continuous infusion of remifentanil. Myogenic motor-evoked responses to
      transcranial electrical stimulation of the motor cortex were recorded. The
      minimum voltage required to elicit maximal amplitude of the MEP response was
      determined. Voltage requirements were compared using the Mann-Whitney U rank sum
      test. P < 0.05 was considered statistically significant. RESULTS: No significant
      difference was found in the minimal voltage needed to elicit maximum amplitude of
      the MEP response. Median (range) voltage requirements in the ketamine and control
      groups were 227 V (range, 160-350 V) and 215 V (range, 150-300 V), respectively.
      CONCLUSION: Addition of low-dose ketamine to propofol/remifentanil anesthesia
      does not significantly reduce the voltage needed to elicit maximum amplitude of
      the motor-evoked response to transcranial electrical stimulation.

PMID- 18090071
TI  - The paraspinal splitting approach: a possible approach to perform multiple
      intercosto-lumbar neurotizations: an anatomic study.
AB  - STUDY DESIGN: Descriptive anatomy. OBJECTIVE.: To describe the anatomy associated
      with the extensive transmuscular paraspinal approach required to perform multiple
      intercosto-lumbar neurotizations. SUMMARY OF BACKGROUND DATA: Neurotization of
      lumbar roots using lower intercostal nerves is a potential method of treating
      neurologic deficits after spinal cord injury. It appeared to us that the
      paraspinal splitting approach was potentially an optimal method to perform
      intercostal nerve harvesting, rerouting, and intercosto-lumbar neurotizations.
      METHODS: Ninth, 10th, and 11th intercostal nerve harvesting and rerouting down to
      L2, L3, and L4 roots were performed on 50 cadavers. The descriptive anatomy and
      topographic landmarks are reported. RESULTS: The mean total length of intercostal
      nerve harvested was 17.96 (range, 10-27) cm for the 9th intercostal nerve, 17.14
      cm (range, 10-20) for the 10th intercostal nerve and 15.94 cm (range, 10-25) for
      the 11th intercostal nerve. The length of harvested nerve was not correlated to
      the size of the trunk. The length of harvested nerve was sufficient to perform
      lumbar roots neurotizations in the 300 cases of nerve harvesting. CONCLUSION:
      Multiple lumbar roots neurotizations with lower intercostal nerves already have
      been proposed by other authors. In this strategy, the use of the spinal cord and
      intercostal nerves above the spinal cord lesion avoids the axonal regrowth
      required via the injured central nervous system. Rerouting intercostals nerves
      down to the lumbar roots at their exit from the intervertebral foraminae is less
      invasive that the same procedure performed down to the vertebral canal at the
      level of the cauda equina as we used in previous protocols. Our anatomic study
      confirms the advantage of the paraspinal sacrospinalis splitting approach in
      multiple intercosto-lumbar neurotizations. The approach is quick and easy and
      allows a good exposure of the nerve roots at the thoracic and lumbar levels. The
      L2, L3, and L4 roots could be satisfactorily neurotized with this procedure.

PMID- 18090072
TI  - Segmental abdominal wall paresis caused by lateral low thoracic disc herniation.
AB  - STUDY DESIGN: Clinical, radiologic, and neurophysiologic description of 2 cases.
      OBJECTIVE: To describe 2 cases with spontaneous deep unilateral abdominal pain as
      the first symptom of thoracic disc herniation at a low thoracic vertebral level,
      further manifested by unilateral partial paresis of the obliquus abdominis
      muscle. SUMMARY OF BACKGROUND DATA: Clinical manifestation of lateral thoracic
      disc herniation with electrophysiologic results and conservative therapy as
      treatment of choice when spinal cord functions are preserved. METHODS: Magnetic
      resonance imaging revealed bilateral paramedian disc protrusions at T12-L1 in
      Patient 1 and foraminal herniation at T10-T11 and paramedian herniation at T11
      T12 in Patient 2. Electromyography (EMG) and evoked potentials were investigated
      in the acute stage and after 6 months. RESULTS: Spontaneous activity on needle
      EMG confirmed axonal root impairment. Somatosensory and motor-evoked potentials
      were within normal limits and excluded spinal cord involvement. Nonsteroidal anti
      inflammatory drugs and periradicular injection of steroids and local anesthetics
      rendered both patients pain-free. Normalization of muscle strength within 3 to 6
      months was accompanied by EMG findings of reinnervation. CONCLUSION: Lateral disc
      herniation causing compression of a thoracic root associated with unilateral
      segmental paresis of the abdominal wall is a rare condition. Despite EMG
      documentation of axonal root lesion, however, a purely conservative therapeutic
      approach may be considered treatment of choice in cases without spinal cord
      involvement.

PMID- 18090073
TI  - Brachial neuritis: an under-recognized cause of upper extremity paresis after
      cervical decompression surgery.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To identify an alternative etiology for the
      development of upper extremity weakness after cervical spine surgery. SUMMARY OF
      BACKGROUND DATA: The development of proximal upper extremity paresis after
      cervical decompression surgery is commonly diagnosed as postoperative C5 palsy.
      Symptoms most commonly consist of weakness involving the deltoid and/or biceps
      brachii muscles, and in many patients there is also associated pain in the
      shoulder region with or without sensory deficits. Interestingly, the onset of
      symptoms is often delayed until days to weeks after surgery. The pathogenic
      mechanisms underlying postoperative C5 palsy remain unclear, although direct
      injury to the nerve root during surgery or a traction injury from a tethering
      phenomenon are frequently cited. These explanations seem unlikely, however, given
      the delayed onset of symptoms. METHODS: Two patients who underwent cervical
      decompression surgery with subsequent development of shoulder pain associated
      with proximal upper extremity weakness are presented. RESULTS: Based on clinical
      presentation and nerve conduction/EMG studies, both patients were diagnosed with
      brachial neuritis. This article describes an alternative diagnosis for the
      constellation of symptoms typically attributed to postoperative C5 palsy.
      Specifically, brachial neuritis is a type of peripheral neuropathy that involves
      the sudden onset of pain in the shoulder girdle followed by weakness, most
      commonly of the deltoid and spinati muscles. CONCLUSION: Brachial neuritis
      appears to be an under-recognized cause of delayed-onset shoulder pain associated
      with upper extremity weakness that develops as a consequence of the stress of
      surgery rather than as a complication of surgical technique.

PMID- 18090074
TI  - Acquired spondylolysis after implantation of a lumbar ProDisc II prosthesis: case
      report and review of the literature.
AB  - STUDY DESIGN: A case of acquired lumbar spondylolysis following lumbar disc
      arthroplasty L5-S1 in an 40-year-old woman and review of the literature.
      OBJECTIVES: To present and discuss a case of acquired lumbar spondylolysis after
      implantation of an artificial disc L5-S1 that may have impaired a good clinical
      result requiring additional posterior lumbar instrumentation and fusion in order
      to improve understanding of this condition and to propose an effective method of
      surgical management. SUMMARY OF BACKGROUND DATA: Lumbar disc arthroplasty is a
      possible surgical option for patients with degenerative disc disease. Acquired
      spondylolysis is a rare but known complication of spinal fusion but has never
      been described as a consequence of mobile disc arthroplasty. The authors present
      the first case in the literature who developed this complication. METHODS: A 40
      year-old woman with severe osteochondrosis L5-S1 and discogenic lumbar back pain
      underwent implantation of an artificial disc. Surgery and postoperative course
      were uneventful and the patient improved significantly as for back pain and
      mobility. Eighteen months after surgery, the patient was again admitted to our
      outpatient clinic for back pain that had slowly increased over time. RESULTS: The
      radiologic workup showed a new spondylolysis L5 without a spondylolisthesis.
      Because of unsuccessful conservative treatment, the patient underwent posterior
      lumbar instrumentation and fusion L5-S1, leading to a significant pain reduction
      and a good clinical outcome. CONCLUSION: Spine surgeons should be aware of the
      possibility of lumbar disc arthroplasty to induce acquired spondylolysis
      impairing good clinical results.

PMID- 18090075
TI  - Delayed symptomatic presentation of epidural hematoma after epidural catheter
      anesthesia: case report.
AB  - STUDY DESIGN: The authors present a case report of a 70-year-old woman who
      presented with delayed symptoms of epidural hematoma after epidural catheter
      anesthesia. OBJECTIVE: We intend to report a unique case of delayed presentation
      of epidural hematoma after epidural catheter anesthesia. SUMMARY OF BACKGROUND
      DATA: The authors present a case of a 70-year-old woman who received epidural
      anesthesia via spinal catheter infusion before right knee replacement surgery.
      After an unremarkable postoperative course, she presented 6 weeks later with
      worsening middle and lower back pain, prompting a workup and lumbar MR imaging.
      MRI of her lumbar spine demonstrated a lower thoracic epidural fluid collection
      with significant radiographic mass effect on the thoracic spine. The fluid was
      diagnosed as chronic breakdown of an initially asymptomatic epidural hematoma.
      Symptomatic epidural hematoma formation after epidural block is rare but commonly
      reported in the literature. The incidence of asymptomatic hematoma formation is
      probably much higher and unrecognized. METHODS: This is a retrospective review of
      a case seen at our institution. RESULTS: A persistent epidural fluid collection
      in a normocoagulable patient presenting with symptoms of back pain more than a
      month after spinal block has not been reported in the literature. CONCLUSION: In
      the absence of focal neurologic symptoms, conservative therapy and observation
      are appropriate.

PMID- 18090077
TI  - Medicare Evidence Development and Coverage Advisory Committee Meeting on lumbar
      fusion surgery for treatment of chronic back pain from degenerative disc disease.

PMID- 18090078
TI  - Circumferential fusion is dominant over posterolateral fusion in a long-term
      perspective: cost-utility evaluation of a randomized controlled trial in severe,
      chronic low back pain.
AB  - STUDY DESIGN: Cost-utility evaluation of a randomized, controlled trial with a 4-
      to 8-year follow-up. OBJECTIVE: To investigate the incremental cost per quality
      adjusted-life-year (QALY) when comparing circumferential fusion to posterolateral
      fusion in a long-term, societal perspective. SUMMARY OF BACKGROUND DATA: The cost
      effectiveness of circumferential fusion in a long-term perspective is uncertain
      but nonetheless highly relevant as the ISSLS prize winner 2006 in clinical
      studies reported the effect of circumferential fusion superior to the effect of
      posterolateral fusion. A recent trial found no significant difference between
      posterolateral and circumferential fusion reporting cost-effectiveness from a 2
      year viewpoint. METHODS: A total of 146 patients were randomized to
      posterolateral or circumferential fusion and followed 4 to 8 years after surgery.
      The mean age of the cohort was 46 years (range, 20-65 years); 61% were females,
      49% were smokers, 30% had primary diagnosis of isthmic spondylolisthesis, 35% had
      disc degeneration and no previous surgery, and 35% had disc degeneration and
      previous surgery. Eighty-two percent of patients have had symptoms for more than
      2 years and 50% were out of the labor market due to sickness. The EQ-5D
      instrument was applied for the measurement of health-related quality of life and
      costs (2004 U.S. dollars) were measured in a full-scale societal perspective.
      Productivity costs were valued by the Friction Cost method, and both costs and
      effects were discounted. Arithmetic means and 95% bias-corrected, bootstrapped
      confidence intervals were reported. Nonparametric statistics were used for tests
      of statistical significance. Comprehensive sensitivity analysis was conducted and
      reported using cost-effectiveness acceptability curves. RESULTS: The
      circumferential group demonstrated clinical superiority over the posterolateral
      fusion group in functional outcome (P < 0.01), fusion rate (P < 0.04), and number
      of reoperations (P < 0.01) among others. Cost-utility analysis demonstrated
      circumferential fusion dominant over posterolateral fusion, that is, for each
      QALY gained performing circumferential fusion, the incremental saving was
      estimated at U.S. $49,306 (95% confidence interval, $27,183-$2,735,712). Results
      proved to be strong to various sensitivity analyses; only a differentiated
      underestimation of patients' need for postoperative household help against the
      circumferential approach could alter the dominance; however, still the
      probability of cost-effectiveness was >0.85 given a threshold for willingness to
      pay of U.S. $50,000 per QALY. CONCLUSION: Circumferential fusion is dominant over
      instrumented posterolateral fusion, that is, both being significantly cheaper and
      significantly better in a long-term, societal perspective.

PMID- 18090079
TI  - Qigong and exercise therapy in patients with long-term neck pain: a prospective
      randomized trial.
AB  - STUDY DESIGN: A randomized, controlled, multicenter trial: 1-year follow-up.
      OBJECTIVE: To compare the effectiveness of qigong and exercise therapy in
      subjects with long-term nonspecific neck pain. SUMMARY OF BACKGROUND DATA: The
      evidence for the benefit of treatment programs focusing on persons with long
      term, nonspecific neck pain is conflicting. Several studies have shown support
      for exercise therapy, but the efficacy of qigong has not been scientifically
      evaluated. METHODS: A total of 122 patients were randomly assigned to receive
      either qigong (n = 60) or exercise therapy (n = 62). Most of them were women
      (70%), and the mean age was 44 years. A maximum of 12 treatments were given over
      a period of 3 months. Neck pain frequency and intensity, neck disability (NDI),
      grip strength, and cervical range of motion were recorded before and immediately
      after, at 6 months, and at 12 months after the treatment period. Changes in
      outcome variables were analyzed and dichotomized as improved or
      unchanged/deteriorated. RESULTS: Clinical and demographic characteristics were
      similar among groups at baseline. No differences were found between the 2
      interventions: qigong and exercise therapy. Both groups significantly improved
      immediately after treatment and this was maintained at the 6- and 12-month follow
      ups in 5 of 8 outcome variables: average neck pain in the most recent week,
      current neck pain (with exception for immediately after treatment period), neck
      pain diary, NDI, and cervical range of motion in rotation. CONCLUSION: These
      results indicate that treatments including supervised qigong or exercise therapy
      resulting in reduced pain and disability can be recommended for persons with long
      term nonspecific neck pain.

PMID- 18090080
TI  - Pedicle and spinal canal parameters of the lower thoracic and lumbar vertebrae in
      the achondroplast population.
AB  - STUDY DESIGN: Retrospective morphometric population study. OBJECTIVE: To
      characterize pedicle and spinal canal morphology of the achondroplastic lower
      thoracic and lumbar vertebrae and to suggest dimensions for improving pedicle
      screw selection and placement. SUMMARY OF BACKGROUND DATA: Although morphometric
      population studies exist for various races, to our knowledge, no such analysis
      has been made in achondroplastic patients. METHODS: With computer software, we
      measured pedicle parameters on the computed tomography images of 19 adult
      achondroplastic patients. RESULTS: Pedicle and chord lengths ranged from 9.5-12.5
      mm and 29.5-36.4 mm, respectively. Transverse pedicle diameter increased from T9
      (5.5 mm) to L5 (14.2 mm). Sagittal pedicle diameter declined from L1 (11.6 mm) to
      L5 (7.8 mm). Transverse angulation was greatest at L5 (15.7 degrees ) and
      smallest at T12 (1.1 degrees ). Pedicles were directed cranially at all levels,
      ranging from 3.8 degrees -15.6 degrees . Interpedicular distance and cross
      sectional area were smallest at L4 (14.9 mm and 119 mm, respectively). Pedicle
      starting points diverged from T9 (13.6 mm) to L5 (19.2 mm2). CONCLUSION:
      Achondroplastic pedicle morphology differs markedly from those of the normal
      spine: chord lengths are substantially shorter, pedicles are inclined cranially,
      pedicle starting points diverge progressively in the lumbar spine, and pedicle
      shape transitions from vertically to horizontally oriented ellipsoids along the
      lumbar spine. Consideration of this variation could maximize the effectiveness
      and safety of pedicle instrumentation.

PMID- 18090081
TI  - Evaluation of posterolateral spinal fusion using mesenchymal stem cells:
      differences with or without osteogenic differentiation.
AB  - STUDY DESIGN: An animal study to achieve posterolateral intertransverse process
      spine fusion using mesenchymal stem cell (MSC). OBJECTIVE: We investigated the
      effectiveness of graft material for spinal fusion using a rabbit model by
      examining the MSC with or without osteogenic differentiation. SUMMARY OF
      BACKGROUND DATA: Posterolateral spinal fusion is commonly performed. Autogenous
      bone graft is the gold standard, although various problems are reported.
      Recently, MSCs from bone marrow have been studied in various fields. Thus, we
      supposed that MSCs have the ability to spinal fusion. METHODS: Twenty-four mature
      male Japanese white rabbits (weight, 3.0-4.0 kg) were divided into 4 groups: 1)
      autologous bone (AG), 2) hydroxyapatite (HA), 3) MSC, and 4) osteogenic MSC
      (OMSC). Each group underwent fusion of the intertransverse processes. The lumbar
      spine was harvested en bloc, and the fusion mass was evaluated radiographically,
      by manual palpation test, and by histologic analysis at 6 weeks after surgery.
      RESULTS: Fusion success or failure was assumed based on the results from manual
      palpation of the harvested spine. Four of 5 rabbits in the OMSC group, 4 of 6
      rabbits in the AB group, 2 of 6 rabbits in the MSC group, and none of 6 rabbits
      in the HA group achieved fusion. In the OMSC group and AG group, new bone
      formation was observed histologically. In the HA group, fibrous tissue and
      cartilage were observed and there was no new bone. In the MSC group, less mature
      bone formation was present in the grafted fragments. CONCLUSION: The present
      study suggested that MSCs that have been cultured with osteogenic differentiation
      medium may induce the formation of new bone in experimental spinal fusion.
      Further studies are needed to determine the suitable level of osteogenic
      differentiate of MSC as well as the most appropriate carrier for MSC.

PMID- 18090082
TI  - Staged-injection procedure to prevent cement leakage during vertebroplasty: an in
      vitro study.
AB  - STUDY DESIGN: Fibrin sealant (FS) combined with or without growth factor was used
      to improve the micro-architectural and biomechanical properties of vertebral body
      in osteoporotic ovine spine. OBJECTIVE: To analyze the treatment effects of
      bovine bone morphogenetic protein (bBMP) combined with FS on osteopenic ovine
      vertebral architecture, bone mineral density, and biomechanics in vivo. SUMMARY
      OF BACKGROUND DATA: Vertebroplasty and kyphoplasty were used to treat spinal
      osteoporosis. They can increase strength of vertebrae physically. However, each
      has specific disadvantages. bBMP could rapidly increasing bone formation and
      suppressing bone resorption, but little is known about its effect on
      ovariectomized-induced osteoporosis. METHODS: Six sheep underwent ovariectomy and
      were placed on a low-calcium diet. Twelve months later, according to Ladin square
      design, L4-L6 vertebrae in all sheep were randomly assigned to 3 treatment
      groups: A (30 mg bBMP/1.5 mL FS), B (30 mg bBMP) and C (1.5 mL FS). All materials
      were injected into the assigned vertebra transpedicularly. Animals were killed 3
      months after injection, and bone mineral density (BMD), biomechanics, and
      histomorphometry were assessed. Analysis of variance was used to determine
      effects of bBMP/FS (alpha = 0.05). RESULTS: The BMD in Group 1 was 17.1% and
      14.7% higher than that in Group 2 and Group 3, respectively. The micro-CT
      reconstruction analysis showed that the density and connectivity of trabecular
      bone in bBMP/FS treated vertebrae were higher than those in control groups. The
      mechanical properties (yield stress, ultimate stress, energy absorption, bone
      modulus) of the vertebrae were also significantly higher. In this study, local
      bBMP/FS treatment showed a positive trend in improving BMD, histomorphometric
      parameters, and mechanical strength of osteoporotic vertebra. Slow release of
      bBMP using FS appeared to be an effective method of protein delivery. CONCLUSION:
      The use of bBMP/FS in the treatment of vertebral osteoporosis in an attempt to
      enhance bone strength merits further study.

PMID- 18090083
TI  - The apoptotic effects of oxidative stress and antiapoptotic effects of caspase
      inhibitors on rat notochordal cells.
AB  - STUDY DESIGN: Western blotting and flow cytometric analyses were performed using
      rat notochordal cells. OBJECTIVE: To demonstrate the apoptotic effect of
      oxidative stress and the antiapoptotic effects of caspase inhibitors on rat
      notochordal cells. SUMMARY OF BACKGROUND DATA: Although oxidative stress causes
      apoptosis in many cell types, its effect on the apoptosis of notochordal cell and
      antiapoptotic effects of caspase inhibitors on the oxidative stress-induced
      apoptosis are unknown. METHODS: Cultured rat notochordal cells were exposed to
      oxidative stress [500 micromol/L of hydrogen peroxide (H2O2)]. To determine the
      oxidative stress-induced apoptotic pathways, activations of caspases (-3, -8, and
      -9) as well as cleavages of Bid and poly (ADP-ribose) polymerase (PARP) were
      evaluated with Western blotting 6 hours after oxidative stress. To elucidate the
      antiapoptotic effects of caspase inhibitors on the oxidative stress induced
      apoptosis, apoptotic rates of notochordal cells with or without treatment of
      specific caspase inhibitors (z-IETD-fmk for caspase-8, z-LEHD-fmk for caspase-9,
      and z-DEVD-fmk for caspase-3) were quantified by flow cytometry. RESULTS:
      Oxidative stress significantly increased apoptosis of rat notochordal cells (2.1%
      vs. 4.75%, P = 0.008) and led to activations of initiators of intrinsic (caspases
      9) and extrinsic (caspase-8) pathways as well as their common executioner
      (caspase-3). It also caused cleavages of Bid and PARP. Flow cytometric analysis
      showed that inhibition of only one of the intrinsic and extrinsic pathways by
      caspase-9 inhibitor (4.75% vs. 3.56%, P = 0.31) and caspase-8 inhibitor (4.75%
      vs. 5.24%, P = 0.84) did not significantly suppress the oxidative stress-induced
      apoptosis. However, inhibition of both pathways by caspase-3 inhibitor
      significantly reduced the oxidative stress-induced apoptosis (4.75% vs. 2.64%, P
      = 0.008) to the control level (2.1% vs. 2.64%, P = 0.15). CONCLUSION: Oxidative
      stress caused apoptosis of rat notochordal cells via both intrinsic and extrinsic
      (Type I and Type II) pathways. Because caspase inhibitors are being used in
      clinical trials, inhibition of both pathways using caspase inhibitors might be of
      future therapeutic importance in oxidative stress-induced apoptosis of
      notochordal cells. Our results suggest that inhibition of inappropriate or
      premature oxidative stress-induced apoptosis of notochordal cells may delay the
      starting point of disc degeneration.

PMID- 18090084
TI  - Abnormal spreading and subunit expression of junctional acetylcholine receptors
      of paraspinal muscles in scoliosis associated with syringomyelia.
AB  - STUDY DESIGN: A comparative study was performed among 2 groups of patients: Group
      A with scoliosis and syringomyelia and Group B with idiopathic scoliosis.
      OBJECTIVE: To investigate the denervation of paraspinal muscles and analyze its
      association with scoliosis in patients with syringomyelia. SUMMARY OF BACKGROUND
      DATA: The mechanism by which scoliosis develops secondary to syringomyelia
      remains unclear. Some authors hypothesize that scoliosis may be caused by an
      alteration in the innervation of the trunk musculature. Few studies, however,
      have been reported to testify the presence of denervation of the paraspinal
      muscles in scoliotic patients with syringomyelia. METHODS: Forty-one children
      were enrolled in the study and were divided into 2 groups. Group A consisted of
      25 patients with scoliosis associated with syringomyelia. Group B included 16
      adolescents with idiopathic scoliosis. Bilateral biopsy of paraspinal muscles was
      performed during scheduled spinal surgery. Distribution of acetylcholine
      receptors (AChRs) and acetylcholinesterase was investigated by immunofluorescence
      staining. RT-PCR was performed to determine the AChRs subunit mRNA expression.
      RESULTS: Immunostaining showed that 56% patients in Group A were scored positive
      for the loss of localization of AChRs to neuromuscular junction, while all Group
      B patients were negative. gamma-AChR subunit expression was detected in 65%
      patients in Group A while absent in all samples in Group B. There was no
      statistical significance of both the positive rate of abnormal spreading and that
      of gamma subunit expression of AChRs between the convex and concave side in Group
      A. CONCLUSION: The denervation of paraspinal muscles is present in some patients
      with scoliosis associated with syringomyelia. The size of the syrinx and the
      degree of cerebellar tonsillar descent might seem to have no relation to the
      denervation of paraspinal muscles.

PMID- 18090085
TI  - When are intervertebral discs stronger than their adjacent vertebrae?
AB  - STUDY DESIGN: Mechanical testing of cadaveric tissues. OBJECTIVE: To compare the
      strength of discs and vertebrae from the same spines in order to determine which
      are more vulnerable to injury, and to determine how their relative vulnerability
      depends on age and gender. SUMMARY OF BACKGROUND DATA: Vertebrae can strengthen
      and weaken according to mechanical demands, but the avascular intervertebral
      discs may be unable to "keep up." Little is known about the relative strength of
      discs and vertebrae. METHODS: Forty-seven thoracolumbar motion segments were
      obtained from 30 cadavers 48 to 91 years of age. Each was compressed until a
      vertebra fractured, and vertebral yield compressive stress (force per unit area)
      was calculated. Adjacent undamaged intervertebral discs were removed, and
      circumferential slices, 2.2 mm thick, were cut from the inner, middle, and outer
      regions of the anterolateral anulus. Slices were stretched to failure to
      determine their ultimate tensile stress. RESULTS: Yield compressive stress of
      male and female vertebrae decreased by 69% and 75%, respectively, in the age
      range of 48 to 91 years (P < 0.001). In contrast, the ultimate tensile stress of
      the adjacent anulus did not fall significantly with age, except in the outer
      region of male discs, where it fell by 66% (P < 0.01). Disc strength was
      proportional to vertebral strength, but only for the outer anulus, and in male
      spines (r2= 24%, P = 0.019, n = 22). CONCLUSION: The outer anulus can adapt to
      mechanical demands because it is the most metabolically active region of the
      disc. Disc and bone properties are better matched in male spines because male
      vertebrae are less affected by variable hormonal changes. The low adaptive
      potential of intervertebral discs makes them relatively weak in the strengthening
      spines of young men but relatively strong in the weakening spines of elderly
      women.

PMID- 18090086
TI  - The effect of removing the lateral part of the pars interarticularis on stress
      distribution at the neural arch in lumbar foraminal microdecompression at L3-L4
      and L4-L5: anatomic and finite element investigations.
AB  - STUDY DESIGN: The assessment of L3 and L4 pars interarticularis thickness and
      finite element analysis of stress distribution across L3 and L4 pars
      interarticularis. OBJECTIVE: To quantify the morphology of the region of the L3
      and L4 pars interarticularis and to assess the stress increase as a function of
      access size using the finite element lumbar spine model. SUMMARY OF BACKGROUND
      DATA: Inadequate decompression and traction of the nerve structures are several
      causes of the unsatisfactory outcomes in patients after foraminal stenosis
      decompression and far lateral disc herniation removal by extraforaminal exposure.
      Enlarging the access of the foraminal exposure by the removal of the lateral
      aspect of the pars interarticularis may be able to diminish the inadequate
      decompression and traction of the nerve structures; however, it may lead to
      increase stress and fracture of the neural arch. METHODS: We used 15 human
      cadaver L3 and L4 lumbar vertebrae for measuring the thickness of the pars
      interarticularis. The ventral and dorsal surfaces were subdivided into 4 equal
      parts, and the thickness of each part was measured using a digital caliper. An
      experimentally validated 3-dimensional nonlinear finite element model of the
      intact L3-S1 segment was used to simulate the lateral removal of one fourth and
      one half of the L3 and L4 pars interarticularis. RESULTS: The mean thicknesses of
      the pars interarticularis showed a gradual increase toward the lateral edge.
      Finite element model analyses predicted stresses increased to 35% and 40% after
      removal of one half of the lateral part of the L3 and L4 pars interarticularis,
      respectively, and were much closer to the intact spine after removal of one
      fourth of the lateral part of the pars interarticularis. CONCLUSION: The removal
      of one fourth of the lateral aspect of the pars interarticularis has minimal
      influence on the stresses in the remaining L3 and L4 neural arches. The lateral
      half of the pars has the largest thickness, and its removal leads to considerable
      stress increases.

PMID- 18090087
TI  - Mechanism of cervical spinal cord injury during bilateral facet dislocation.
AB  - STUDY DESIGN: An in vitro biomechanical study. OBJECTIVES: The objectives were
      to: quantify dynamic canal pinch diameter (CPD) narrowing during simulated
      bilateral facet dislocation of a cervical functional spinal unit model with
      muscle force replication, determine if peak dynamic CPD narrowing exceeded that
      observed post-trauma, and evaluate dynamic cord compression. SUMMARY OF
      BACKGROUND DATA: Previous biomechanical models are limited to quasi-static
      loading or manual ligament transection. No studies have comprehensively analyzed
      dynamic CPD narrowing during simulated dislocation. METHODS: Bilateral facet
      dislocation was simulated using 10 cervical functional spinal units (C3-C4: n =
      4; C5-C6: n = 3; C7-T1: n = 3) with muscle force replication by frontal impact of
      the lower vertebra. Rigid body transformation of kinematic data recorded
      optically was used to compute the CPD in neutral posture (before dislocation),
      during dynamic impact (peak during dislocation), and post-impact (flexion
      rotation = 0(0) degrees ). Peak dynamic impact and post-impact CPD narrowing were
      statistically compared. RESULTS: Average peak dynamic impact CPD narrowing
      significantly exceeded (P < 0.05) post-impact narrowing and occurred as early as
      71.0 ms following impact. The greatest dynamic impact narrowing of 7.2 mm was
      observed at C3-C4, followed by 6.4 mm at C5-C6, and 5.1 mm at C7-T1, with average
      occurrence times ranging between 71.0 ms at C7-T1 and 97.0 ms at C5-C6.
      CONCLUSION: Extrapolation of the present results indicated dynamic spinal cord
      compression of up to 88% in those with stenotic canals and 35% in those with
      normal canal diameters. These results are consistent with the wide range of
      neurologic injury severity observed clinically due to bilateral facet
      dislocation.

PMID- 18090088
TI  - Prognostic factors for deterioration of patients with cervical spondylotic
      myelopathy after nonsurgical treatment.
AB  - STUDY DESIGN: A prospective study involving 56 patients with cervical spondylotic
      myelopathy (CSM) was conducted. OBJECTIVE: To investigate the outcomes and
      prognostic factors for CSM after nonsurgical treatment. SUMMARY OF BACKGROUND
      DATA: The superiority of surgical treatment over nonsurgical treatment has not
      been confirmed in mild forms of CSM. Outcomes and prognostic factors for
      nonsurgical treatment of mild forms of CSM are not well understood. METHODS:
      Clinical signs and symptoms of CSM were assessed by Japanese Orthopedic
      Association (JOA) scores. Nonsurgical treatment was selected for patients with
      mild forms of CSM (JOA >or=13 patients). Seventy patients with mild forms of CSM
      were enrolled in the study between 1995 and 2003. The follow-up rate was 80.0%.
      Prognostic factors that exacerbate clinical symptoms of CSM were examined, such
      as age, gender, follow-up period, developmental or dynamic factors on plain
      lateral radiograph, high signal intensity area on T2-weighted sagittal MRI, and
      the extent of maximum cord compression; partial or circumferential spinal cord
      compression, on axial MRI. Univariate and multivariate logistic regression
      analysis were carried out to test for significant prognostic factors. RESULTS:
      There was, on average, no statistically significant deterioration in JOA scores
      after nonsurgical treatment. However, 11 of 56 patients deteriorated after
      nonsurgical treatment. The only factor that significantly exacerbated clinical
      symptoms of CSM was circumferential spinal cord compression in the maximum
      compression segment on axial MRI. Indeed, 10 of 33 CSM patients with
      circumferential spinal cord compression on axial MRI deteriorated after
      nonsurgical treatment. CONCLUSION: Outcomes of mild forms of CSM during
      nonsurgical treatment were generally good as shown by average JOA scores. The
      only prognostic factor for mild forms of CSM was circumferential spinal cord
      compression in the maximum compression segment on axial MRI. Surgical treatment
      can be considered for patients with this prognostic factor.

PMID- 18090089
TI  - Hematogenous methicillin-resistant Staphylococcus aureus spondylodiscitis.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To determine relevant
      demographics, clinical presentations, and outcomes of this condition. SUMMARY OF
      BACKGROUND DATA: This is the first study looking specifically at methicillin
      resistant Staphylococcus Aureus (MRSA) spondylodiscitis. METHODS: We performed a
      retrospective review of patients presenting between 2000 and 2005. RESULTS:
      Thirteen cases were identified. The mean age was 65 years; 85% were male. All
      cases presented with back pain, spinal tenderness, and systemic upset. Neurologic
      deficit was present initially in 39%, and 8% developed neurologic deterioration
      during treatment. The thoracic spine (53%) was most commonly affected, followed
      by the lumbar (33%), thoracolumbar junction (7%), and cervical spine (7%); 16% of
      cases were multilevel. The white cell count, erythrocyte sedimentation rate and C
      reactive protein were elevated in all cases with means of 17.3 x 10(-9)/L, 102
      mm/h, and 236 mg/L, respectively. Radiologic diagnosis was established with MRI
      in all cases. The most common risk factors were diabetes mellitus (62%),
      malnourishment (54%), cirrhosis (31%), end-stage renal failure (15%), and
      intravenous drug use (15%). Multiple risk factors were present in 76% of cases,
      and only 15% had no identifiable risk factors. The main sources of sepsis were
      intravenous catheters (23%), urinary tract (15%), and intravenous drug use (15%).
      Treatment consisted of intravenous vancomycin monotherapy for a mean period of 4
      weeks followed by oral combination or monotherapy antimicrobials for a mean
      period of 8 weeks. Operative intervention was required in 38% of cases. At 6
      months, 54% of cases were clinically free of infection, 38% had died, and 8%
      required ongoing treatment. Neurologic deficit was present in 50% of survivors.
      At 1 year, 29% of survivors had MRSA bacteremia and spondylodiscitis recurrence.
      CONCLUSION: This is a devastating condition with high mortality and morbidity.

PMID- 18090090
TI  - A vertebral fracture in childhood is not a risk factor for disc degeneration but
      for Schmorl's nodes: a mean 40-year observational study.
AB  - STUDY DESIGN: Observational cohort study. OBJECTIVE: To evaluate by MRI whether a
      vertebral fracture during childhood is a risk factor for degeneration of adjacent
      discs. SUMMARY OF BACKGROUND DATA: Several studies infer that trauma is a major
      cause of disc degeneration. Only 1 study has by magnetic resonance imaging (MRI)
      evaluated disc degeneration in children with a former thoracic or lumbar
      vertebral fracture. That study reported a 50% prevalence of degenerative disc
      changes 4 years after the fracture. However, due to the sparse literature, it is
      still unclear whether a vertebral fracture in childhood represents a risk factor
      for disc degeneration in a long-term perspective. METHOD: Nine boys and 11 girls
      with a mean age of 12 years (range, 7-16 years) when sustaining a lumbar or
      thoracic vertebral fracture without neurologic deficits were examined at a mean
      of 40 years (range, 33-53 years) after the injury. Eighteen of the subjects had 1
      column compression fractures, and 2 had Denis Type B burst fractures. All were
      mobilized without brace or surgery directly after being injured. A favorable long
      term clinical and plain radiographic outcome has previously been reported for
      this cohort. In the present study, the intervertebral discs were evaluated with
      MRI by applying the Oner classification scheme. Degenerative disc changes were
      defined as loss of signal intensity on T2-weighted images with or without disc
      height reduction. RESULTS: Degenerative changes were not more prevalent in discs
      adjacent to the previously fractured vertebrae than in discs at a distance from
      those segments. However, there were more Schmorl's nodes at the disc levels
      adjacent to the earlier fractures. CONCLUSION: Stable vertebral fractures in
      childhood with no neurologic deficits at injury do not render more degenerative
      changes than can be expected according to age, but they are associated with more
      Schmorl's nodes at adjacent disc levels.

PMID- 18090091
TI  - Retrospective review of multilevel spinal fusion combined with spinal cord
      transection for treatment of kyphoscoliosis in pediatric myelomeningocele
      patients.
AB  - STUDY DESIGN: Retrospective review of cases at a single institution from 1998 to
      2005. OBJECTIVE: The authors present their surgical experience, complications,
      and learned insight in 9 myelomeningocele children with kyphoscoliosis treated
      with combined spinal cord transection and spinal fusion. SUMMARY OF BACKGROUND
      DATA: Complication rates in spinal fusion for treatment of kyphoscoliosis in
      myelomeningocele patients are high. Spinal cord transection in combination with
      fusion can be an appropriate strategy in selected patients, but changes in
      cerebrospinal fluid (CSF) dynamics that may accompany ligation of the distal CSF
      circulation are not well characterized. METHODS: Demographic, clinical, and
      radiologic data were examined in 9 children with myelomeningocele level at or
      above T12 and no residual urologic function treated at our institution with
      spinal cord detethering and transection, and multilevel spinal fusion. Seven
      children underwent kyphectomy with posterior fusion only for severe gibbus
      deformities, while 2 had anterior and posterior fusions for severe
      kyphoscoliosis. RESULTS: Follow-up of patients ranged from 4 to 92 months (mean,
      37.8 months). Eight children (89%) experienced postoperative complications
      involving wound infection or skin breakdown. One child presented with a CSF leak.
      Two children (22%) required revision of their ventriculoperitoneal shunts. The
      average angle of kyphosis before surgery was 122.3 (range, 48 degrees -180
      degrees ), and the average postoperative angle was 38.2 (range, 4 degrees -113
      degrees ), with average correction being 81.9 degrees (range, 29 degrees -124).
      Average correction of scoliosis, if present, was 59.5 degrees (range, 35 degrees 
      92 degrees ). CONCLUSION: Combined spinal cord transection and spinal fusion
      allowed an average correction of kyphosis by 81.9 degrees . The complication rate
      was 89%, with wound concerns being the most significant. Additionally, 22% of
      patients required shunt revision within 6 weeks of surgery. We attribute this to
      alteration of CSF dynamics resulting from loss of CSF absorption and flow
      buffering capacity below the level of the spinal cord transection.

PMID- 18090092
TI  - Spinal deformities in hereditary motor and sensory neuropathy: a retrospective
      qualitative, quantitative, genotypical, and familial analysis of 175 patients.
AB  - STUDY DESIGN: Retrospective study of 175 patients with hereditary motor and
      sensory neuropathy (HMSN), i.e., Charcot-Marie-Tooth (CMT) disease. OBJECTIVE: To
      investigate the frequency, age of onset, character, familial, and genotypical
      incidence of spinal deformities among HMSN patients. SUMMARY OF BACKGROUND DATA:
      Prior studies addressing HMSN discuss the associated spinal deformities. However,
      these data vary significantly while inconsistently including genotypes within the
      classification framework. METHODS: Plain-film radiographic spine studies of 175
      HMSN patients were performed to determine the incidence, character, and severity
      of spinal deformity. The degree of the spinal deformity was evaluated measuring
      Cobb's angle of the main curve. The results of the entire cohort were initially
      assessed before being classified by genotype. RESULTS: The incidence of spinal
      deformity for the entire group was 26%. Of these, 58% demonstrated scoliosis, 31%
      had kyphoscoliosis, and 11% had thoracic hyperkyphosis; 73% of patients with
      spinal deformity were classified as HMSN Type I with confirmed duplication of the
      PMP 22 (peripheral myelin protein) gene on chromosome 17. The incidence of spinal
      deformity by genotype was: duplication of the PMP 22 gene: 29% (25 of 87);
      deletion of the PMP 22 gene: 0% (0 of 15); Cx32 (connexin 32) gene mutation: 24%
      (8 of 34); and MPZ (myelin protein zero) gene mutation: 100% (6 of 6). Familial
      incidence of spinal deformity was found in "MPZ gene mutation" and "duplication
      of PMP 22 gene" subgroups. CONCLUSION: This study demonstrates a 26% incidence of
      spinal deformity among HMSN patients. Spinal deformity was most frequently
      observed in patients with the MPZ gene mutation, where the most common familial
      incidence was also found.

PMID- 18090093
TI  - Do chiropractors adhere to guidelines for back radiographs? A study of
      chiropractic teaching clinics in Canada.
AB  - STUDY DESIGN: Clinical cohort. OBJECTIVES: To measure the adherence to 3
      radiography guidelines for low back pain in chiropractic teaching clinics.
      SUMMARY OF BACKGROUND DATA: Evidence-based guidelines for low back pain suggest
      that plain radiography should be restricted to patients with suspected serious
      disease. Among primary healthcare providers who can request radiographs,
      chiropractors are thought to have utilization rates that exceed what is
      recommended by practice guidelines. It is uncertain whether this gap between
      evidence and practice begins in undergraduate training. METHODS: We screened 1241
      consecutive patients with a new episode of low back pain who presented to any of
      the 6 out-patient teaching clinics of the Canadian Memorial Chiropractic College
      between January 2004 and September 2004. We collected information about red flags
      and radiography recommendations from patients and chiropractic trainees using
      self-administered questionnaires. Radiography recommendations were compared with
      criteria used in 3 radiography guidelines. Adherence was measured as the
      proportion of patients without red flags who were not recommended for
      radiography. RESULTS: Of the 503 eligible patients, 448 (89.1%) agreed to
      participate in the study. Radiography was recommended for 12.3% of patients.
      According to the selected radiography guidelines, the proportion of patients with
      red flags ranged from 45.3% to 70.5%. The proportion of patients without red
      flags who were not recommended for radiography ranged from 89.4% (95% confidence
      interval, 85.5%-93.2%) to 94.7% (95% confidence interval, 90.9%-98.5%) for the
      selected guidelines. CONCLUSIONS: The results suggest a strong adherence to
      radiography guidelines for patients with a new episode of low back pain who
      presented to chiropractic teaching clinics. Although a high proportion of
      patients had red flags, radiography utilization was lower than rates reported in
      previous studies suggesting that adherence to guidelines may help prevent
      unnecessary radiography.

PMID- 18090094
TI  - Primary jugular foramen meningioma.

PMID- 18090097
TI  - Electrode migration after cochlear implantation.
AB  - OBJECTIVE: To review the occurrence of electrode migration after cochlear
      implantation. STUDY DESIGN: Review of public database and retrospective case
      series. SETTING: Tertiary academic referral center, ambulatory. PATIENTS:
      Retrospective review of electrode migration reported in association with the US
      Food and Drug Administration Manufacturer and User Facility Device Experience
      database and a single-institution case series between 1996 and 2006.
      INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURE: Occurrence of
      electrode migration. RESULTS: During the period 1996 to 2006, 151 reports of
      electrode migration were filed in the Manufacturer and User Facility Device
      Experience database. The most common association with migration was cochlear
      ossification, although 127 of 151 cases had no known association. During an
      equivalent period, 637 cochlear implant (CI) procedures were performed at the
      University of Miami. Of 580 primary CI operations, 2 cases of electrode migration
      were identified, both associated with reossification of a cochlea that was fully
      ossified at the first procedure. CONCLUSION: Electrode migration is an
      underrecognized complication of CI surgery and may be associated with cochlear
      ossification. Electrode stabilization techniques may reduce the incidence of CI
      electrode migration in nonossified or incompletely ossified cases.

PMID- 18090098
TI  - Factors associated with ability to treat pediatric emergencies in US hospitals.
AB  - OBJECTIVE: The purpose of this analysis is to investigate hospital and community
      factors associated with the availability of pediatric services, expertise, and
      supplies in US hospitals for treating pediatric emergencies. METHODS: Data from
      the Emergency Pediatric Services and Equipment Supplement, a component of the
      2002-2003 National Hospital Ambulatory Medical Care Survey, were merged with
      hospital and community characteristics to model preparedness to treat pediatric
      emergencies. The National Hospital Ambulatory Medical Care Survey samples
      nonfederal, short-stay, and general hospitals in the United States. The Emergency
      Pediatric Services and Equipment Supplement was based on the 2001 guidelines
      developed by the American Academy of Pediatrics and the American College of
      Emergency Physicians. Estimates were weighted to produce unbiased national
      estimates of pediatric services, expertise, and equipment availability in
      emergency departments. Logistic regression was used to model the probability of
      being better prepared based on the above guidelines. RESULTS: Bivariate analyses
      showed that hospital inpatient pediatric structure was linearly related to
      availability of supplies. However, inpatient structure was not associated with
      presence of a pediatric trauma service or written transfer agreement. Logistic
      regressions with each preparedness measure indicated that, after adjusting for
      hospital and community factors, pediatric volume, teaching hospital status,
      geographic region, and per capita income of the community were strongly related
      to being better prepared on each of the preparedness measures. CONCLUSIONS: To
      meet the 2001 guidelines, emergency departments need to improve their inventory
      of pediatric supplies, and hospitals that do not have specialized inpatient
      services need to implement written transfer agreements with other hospitals.

PMID- 18090099
TI  - Etomidate versus pentobarbital for computed tomography sedations: report from the
      Pediatric Sedation Research Consortium.
AB  - OBJECTIVE: To compare efficacy, sedation duration, and adverse events after
      administration of etomidate or pentobarbital for diagnostic computed tomography
      (CT) scans. METHODS: A cohort of children sedated for CT scans between July 2004
      and October 2005 was identified from a prospectively generated Pediatric Sedation
      Research Consortium database. The 24 Pediatric Sedation Research Consortium
      institutions prospectively record consecutive sedation data and adverse events on
      a Web-based tool. This study included all patients of American Society for
      Anesthesiologists (ASA) class I or II, between 6 months and 6 years old, sedated
      with etomidate or with intravenous pentobarbital with or without midazolam.
      Outcomes included sedation efficacy, duration (time from drug administration
      until cessation of monitoring), and complication rate. RESULTS: Of 3397 pediatric
      sedations for CT scans, 2587 met age and ASA criteria. Etomidate was administered
      by pediatric emergency physicians as the sole sedative for 446 sedation service
      cases; pentobarbital with or without midazolam was used in 396 sedations by a
      variety of providers. Sedation was "not ideal" for 11 pentobarbital sedations and
      1 etomidate sedation. Median etomidate dose was 0.33 mg/kg (intraquartile rank,
      0.30-0.44 mg/kg); median pentobarbital dose was 4 mg/kg (intraquartile rank, 3.2
      4.8 mg/kg). Mean etomidate sedation (34 minutes; 95% confidence interval [CI], 32
      36 minutes) was shorter than pentobarbital (144 minutes; 95% CI, 139-150
      minutes). Etomidate patients were younger (24 vs. 29 months), whereas
      pentobarbital patients were more often of ASA class II (52% vs. 34%), both P <
      0.001. Adverse events were more common with pentobarbital (4.5% vs. 0.9%;
      relative risk, 3.38%; 95% CI, 1.28%-9.45%). One etomidate and 2 pentobarbital
      patients experienced apnea. CONCLUSIONS: Etomidate as given by emergency
      physicians was more effective and efficient than pentobarbital, with rare adverse
      events.

PMID- 18090100
TI  - Children in methamphetamine homes: a survey of physicians practicing in southeast
      Tennessee.
AB  - OBJECTIVES: Methamphetamine (meth) abuse in the rural South has increased greatly
      in the last decade. This addiction harms meth abusers and producers and endangers
      children who live with them. Appropriate medical evaluation and treatment of
      these exposed children are largely undefined. The objective of this research was
      to ascertain how emergency medical practitioners view this problem and their
      management approaches. METHODS: A survey of medical practices was mailed to 87
      physicians associated with emergency departments and child services in 12
      southeastern Tennessee counties with high rates of meth lab seizures. This survey
      asked about physicians' examination of children in provided clinical scenarios
      who may have been exposed to meth, their assessment of the severity of the meth
      problem in their area, and the utility of a standardized protocol for management.
      Twenty-six practitioners responded. RESULTS: In a clinical scenario developed to
      suggest high possibility of meth exposure, the average response regarding
      likelihood of meth exposure was 8 on a scale of 1 to 10. In a scenario suggesting
      ambiguous exposure, the physicians' mean response about likelihood of meth
      exposure was 4 on a scale of 1 to 10. In a third scenario presenting a confirmed
      meth exposure, physicians ordered the following tests: toxicology screening
      (96%), complete blood count (88%), oxygen saturation (76%), chest radiograph
      (72%), and carboxyhemoglobin concentration (52%). Ninety-two percent of
      respondents felt that medical knowledge of meth could be improved. CONCLUSIONS:
      Southeastern Tennessee emergency practitioners varied in their estimation of the
      likelihood of meth exposure to children in different scenarios. In addition,
      their clinical responses to cases of definite exposure were highly divergent.
      These practitioners also stated that standardized guidelines would aid in
      providing care for meth-exposed children.

PMID- 18090101
TI  - Emergency planning in school-based athletics: a national survey of athletic
      trainers.
AB  - OBJECTIVES: To use nationally published guidelines to examine the preparedness of
      schools in the United States to respond to emergencies associated with school
      based athletics. METHODS: A questionnaire, mailed to 1000 randomly selected
      members of the National Athletic Trainers' Association, included questions on the
      clinical background of the athletic trainer, the demographic features of their
      school, the preparedness of their school to manage life-threatening athletic
      emergencies, the presence of preventative measures to avoid potential sport
      related emergencies, and the immediate availability of emergency equipment.
      RESULTS: Of the 944 questionnaires delivered, 643 (68%) were returned; of these,
      521 (81%) were eligible for analysis (55% usable response rate). Seventy percent
      (95% confidence interval [CI], 66-74) of schools have a Written Emergency Plan
      (WEP), although 36% (95% CI, 30-40) of schools with a WEP do not practice the
      plan. Thirty-four percent (95% CI, 30-38) of schools have an athletic trainer
      present during all athletic events. Sports previously noted to have higher rates
      of fatalities/injuries based on published literature, such as ice hockey and
      gymnastics, had, according to our data, less coverage by athletic trainers
      compared with other sports with lower rates of fatalities/injuries. Athletic
      trainers reported the immediate availability of the following during athletic
      events: cervical spine collar (62%, 95% CI, 58-66), automatic electronic
      defibrillator (61%, 95% CI, 57-65), epinephrine autoinjector (37%, 95% CI, 33
      41), bronchodilator metered-dose inhaler (36%, 95% CI, 32-40). CONCLUSIONS:
      Although schools are in compliance with many of the recommendations for school
      based athletic emergency preparedness, specific areas for improvement include
      practicing the WEP several times a year, linking all areas of the school directly
      with emergency medical services, increasing the presence of athletic trainers at
      athletic events (especially sports with a higher rate of fatalities/injuries),
      regulating the care of and inspection of school facilities and fields, requiring
      the use of safety equipment (such as mouth guards and protective eye equipment),
      and increasing the availability of automatic electronic defibrillator in schools.

PMID- 18090102
TI  - Retrospective comparison of emergency department length of stay for procedural
      sedation and analgesia by nurse practitioners and physicians.
AB  - OBJECTIVES: To determine if use of nurse practitioners (NPs) for procedural
      sedation and analgesia (PSA) compared with physicians (MDs) decreased overall
      length of stay (LOS) in the pediatric emergency department (PED). METHODS:
      Retrospective chart review was conducted on all children (age <21 years)
      undergoing procedural sedation and analgesia (PSA) for 36 consecutive months at a
      tertiary academic children's hospital (n = 690). Data included times values for
      triage, evaluation by practitioner (NP, MD), sedation, discharge, and total LOS
      in the PED. Data collected also included medications given, patient diagnosis,
      and severe airway complications. RESULTS: Results revealed statistically
      significant time-related advantages to NP-managed sedations. Both PED LOS and
      time to sedation were significantly lower for NPs versus MDs across diagnoses (P
      < 0.01). The diagnoses managed by MDs versus NPs were significantly different for
      3 diagnoses: fracture, finger, and lacerations. There were no differences between
      NP and MD for severe airway complication rates. CONCLUSIONS: Overall LOS and time
      to sedation were significantly improved when NPs independently managed patients
      requiring PSA without an increase in documented severe airway complication rates.

PMID- 18090103
TI  - Child-resistant closures for mouthwash: do they make a difference?
AB  - OBJECTIVES: The Poison Prevention and Packaging Act of 1970 mandated that certain
      potentially hazardous drugs and other products be sold in child-resistant
      containers (CRCs). The Consumer Product Safety Commission estimates that CRCs for
      aspirin and oral prescription medicine saved the lives of about 700 children
      since the requirements went into effect in the 1970s. Under this Act, the
      Consumer Product Safety Commission issued a rule requiring child-resistant
      packaging for mouthwashes containing 3 g or more of ethanol per package. The
      effective date was July 24, 1995, and applied to all applicable products packaged
      on or after that date. METHODS: To determine the effectiveness of this 1995
      ruling, all American Association of Poison Control Center Toxic Exposure
      Surveillance System data involving children younger than 6 years who ingested
      ethanol-containing mouthwash 10 years before the implementation of this ruling,
      the transition year, and 10 years after were reviewed. Only single-substance
      exposures were included. Data reviewed included the total number of exposures per
      pre and post years and the outcome. RESULTS: A total of 61,185 cases met the
      criteria. There were 18,275 exposures from 1985 through 1994 prerequirement
      (0.12% of all exposures); 39,376 from 1996 to 2005 postrequirement years (AR)
      (0.17% of all exposures); and 3,534 cases reported in 1995 (0.17% of all
      exposures). Definitive outcomes were coded in 62.6% of the prerequirement group
      and 42.2% of the AR group. CONCLUSIONS: Numerous factors affect these results.
      However, in those cases where definitive outcomes were coded, the AR group has
      better outcomes.

PMID- 18090104
TI  - Unintentional organophosphate intoxication in children.
AB  - OBJECTIVES: To describe the demographic characteristics, clinical course, and
      outcome of children with acute organophosphate (OP) poisoning admitted to a
      regional medical center. METHODS: The clinical charts of all children admitted to
      the pediatric wards in Hadassah University Hospital with a diagnosis of acute OP
      intoxication were reviewed. RESULTS: During the study period (1989-2003), 31
      children, mean age 5.6 +/- 3.9 years, presented with manifestations of acute OP
      poisoning. In 71% of the patients, it was possible to identify the toxin, most
      commonly parathion and diazinone. The most common route of exposure was ingestion
      of agricultural products treated with OPs (71%). The major clinical manifestation
      was neurological, with most of the patients presenting with coma and/or seizures
      (71%). The classic muscarinic and nicotinic signs of intoxication including
      increased secretions, bradycardia, fasciculations, and miosis were less common in
      our patient population. Treatment included decontamination, administration of
      antidote, and supportive care. Most patients responded well to treatment, but 2
      patients (6.4%) died. CONCLUSIONS: The manifestations of OP poisoning in children
      are different from those of adults. Pediatricians should be aware of these
      differences because in some cases, a history of OP exposure is not obtained.

PMID- 18090105
TI  - A 12-month-old infant with Fournier gangrene associated with varicella.
AB  - Fournier gangrene is a progressive infection of the genital and perianal regions.
      It is a truly rare entity in association with varicella. There is only a single
      case published in the literature. We present the second case of a Fournier
      gangrene associated with varicella in an infant.

PMID- 18090106
TI  - Care of the acutely ill pediatric heart transplant recipient.
AB  - Young children may present to the emergency department after undergoing
      orthotopic heart transplantation. Emergency department care of pediatric heart
      transplant recipients with an acute illness is not clearly defined. To assist the
      emergency physician with treating these children, 2 cases are detailed to
      demonstrate the variation in outcome of young children presenting to the
      emergency department with acute illness months after their transplant. The cases
      typify the varied outcomes possible after emergency department presentation.
      After the cases, a review of the medical conditions common in transplant
      recipients precedes a description of management suggestions.

PMID- 18090107
TI  - Ecstasy ingestion causing heatstroke-like, multiorgan injury in a toddler.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) ingestion can cause febrile status
      epilepticus in children but has not been reported to cause multiorgan dysfunction
      seen in young adults. We describe a toddler who was diagnosed at this stage of
      multiorgan injury. This drug, a synthetic amphetamine, has the "street" name of
      "ecstasy" and is commonly used by teenagers and young adults to augment the
      euphoric experience of "raves."

PMID- 18090108
TI  - An asthmatic adolescent with a rash and eosinophilia.
AB  - Children frequently visit emergency departments with asthma exacerbations. Many
      of these asthmatic children may have fever and/or pneumonia, but when associated
      with eosinophilia or evidence of vasculitis, other diagnoses should be
      considered. Churg-Strauss syndrome is a rare form of systemic vasculitis, which
      usually occurs in patients with asthma in association with eosinophilia. The
      diagnosis of Churg-Strauss syndrome can be difficult because this syndrome may
      arise at first as a common association between asthma and allergic rhinitis. A
      delay in diagnosis and treatment may increase the morbidity from the
      complications of vasculitis. We report a young asthmatic adolescent who presented
      with vasculitis, eosinophilia, and peripheral neuropathy.

PMID- 18090109
TI  - Injury by mittens in neonates: a report of an unusual presentation of this easily
      overlooked problem and literature review.
AB  - Injuries caused by mittens applied to infants' hands had been reported since the
      1960s. Despite the attention brought forward, reports of injuries continued to
      appear. We report a case of an unusual presentation of upper limb injuries
      related to mittens, where the injuries involve the entire hand. The injuries
      fortunately recovered within 2 weeks without subsequent tissue loss.

PMID- 18090110
TI  - Frena tears and abusive head injury: a cautionary tale.
AB  - Tears of the lingual and labial frena have been associated with accidental and
      nonaccidental injury. Three cases of infants are presented who were evaluated in
      the hospital with frena tears which were not recognized as manifestations of
      abuse, discharged home, and subsequently returned with manifestations of severe
      abusive head injury.

PMID- 18090111
TI  - Pediatric pedestrian injuries: emergency care considerations.
AB  - Pedestrian traffic injuries are a growing public health threat worldwide. The
      global economic burden of motor vehicle collisions and pedestrian injuries
      approximates $500 billion. In the United States, the number of pedestrian
      fatalities increased from 4675 in 2004 to 4881 in 2005. In addition nearly 60,000
      injuries occurred during the same year. Injury patterns vary depending on the
      age, sex, and socioeconomic status of the individual. Children comprise one of
      the most vulnerable populations in pedestrian traffic injuries. Pedestrian injury
      remains the second leading cause of unintentional injury-related death among
      children aged 5 to 14 years. The burden of injury, upon the individual, families,
      and society, is frequently overwhelming. From recent data, pedestrian injuries
      and deaths are increasing in the United States and the World, and they require
      particular attention by emergency care providers and policy makers.

PMID- 18090114
TI  - Pediatric emergency medicine: legal briefs.

PMID- 18090115
TI  - ECGs in the ED.

PMID- 18090112
TI  - Strategies to improve flow in the pediatric emergency department.
AB  - As emergency departments (EDs) experience overcrowding, there is ever-growing
      pressure to improve patient flow. We present a review of strategies to increase
      efficiency of patient inflow, throughput, and output in the ED, with an emphasis
      on approaches that are under greater control of the ED itself and therefore more
      amenable to implementation without major institutional changes.

PMID- 18090116
TI  - Topical etofenamate to facilitate venipuncture.

PMID- 18090117
TI  - Cystic fibrosis and hypoelectrolytemia.

PMID- 18090120
TI  - Alcohol and liver cancer.

PMID- 18090121
TI  - Glutathione-S-transferase M1 and T1 and cytochrome P1A1 genetic polymorphisms and
      susceptibility to cervical intraepithelial neoplasia in Greek women.
AB  - The aim of the study was to determine the importance of genetic polymorphisms of
      glutathione-S-transferase T1 and M1 and cytochrome P1A1 genes in the development
      of cervical intraepithelial neoplasia in Greek women. This was a prospective,
      case-control study conducted by the Cervical Pathology and Colposcopy Unit of a
      University Ob/Gyn Department from 1999 to 2003. Cervical smears from 114 controls
      without any cytological and/or colposcopical evidence of cervical pathology and
      from 166 women with history of cervical intraepithelial neoplasia (56 CIN I, 54
      CIN II and 56 CIN III) were examined with polymerase chain reaction for the above
      mentioned genetic polymorphisms, taking also in mind their smoking attitudes.
      Statistical analysis was performed to detect any association between the null
      genotype of GSTM1 and GSTT1 genes and the CYP1A1 m1 polymorphism and the severity
      of cervical intraepithelial neoplasia. The distributions of the GSTT1 and GSTM1
      wild-type genotypes were 57.48 and 39.75%, respectively. No woman with homozygous
      GSTT1 and GSTM1 null/null genotype was identified. CYP1A1 m1 polymorphism
      frequency was 24.49%. No woman with homozygous CYP1A1 m1/m1 genotype was detected
      as well. No significant difference in the frequencies of the GSTM1 and GSTT1 null
      alleles, and the CYP1A1 m1 polymorphism, was found between cases and controls.
      After application of Mantel-Haenszel chi procedure, there was no linear severity
      of the lesion and the frequency of these polymorphisms. According to our results,
      glutathione-S-transferase T1 and M1 and cytochrome P1A1 genetic polymporphisms do
      not appear to be a risk factor for cervical disease irrespective of smoking
      habits.

PMID- 18090122
TI  - Efficacy of sulforaphane is mediated by p38 MAP kinase and caspase-7 activations
      in ER-positive and COX-2-expressed human breast cancer cells.
AB  - Sulforaphane is an antioxidant and a potent stimulator of natural detoxifying
      enzyme and associated with lowered risk of cancer that is associated with the
      consumption of cruciferous vegetables. The chemopreventive effects of SFN was
      investigated using the MCF-7 human breast cancer cells and the M13SV1
      immortalized human breast luminal epithelial cells. Sulforaphane reduced
      proliferation in MCF-7 cells and inhibited cyclooxygenase-2 expression in M13SV1
      cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). The
      chemopreventive effects of sulforaphane were associated with p38 mitogen
      activated protein kinase suggest its important role in cell survival/apoptosis
      regulation and stabilization of cyclooxygenase-2. Sulforaphane upregulates p38 in
      MCF-7 cells and prevented TPA-reduced phosphorylation of p38 in M13SV1 cells, but
      activated caspase-7 associated with apoptosis in MCF-7 cells. These results
      suggest that sulforaphane may be an alternative candidate for targeted prevention
      of ER-positive and cyclooxygenase-2-induced phenotypes and breast cancer.

PMID- 18090123
TI  - Neurobiological effects of melatonin as related to cancer.
AB  - Melatonin is a neurohormone naturally found in humans. Melatonin plays a role in
      maintaining sleep-wake rhythms; supplementation may help to regulate sleep
      disturbance that occur with jet lag, rotating shift-work and depression.
      Preliminary study of melatonin has shown potential for use in the treatment of
      epilepsy, tinnitus, migraine and neurodegenerative diseases. The latest
      publication in the Journal of Pineal Research by Edward Mills and colleagues has
      shown a compelling role of melatonin for the treatment of cancer. Melatonin's
      consistent relationship with cancer has been shown in many studies assessing
      links between shift work and cancer rates. High levels of melatonin have been
      linked to slower cancer progression. How melatonin affects cancer remains largely
      unclear. Although previous studies suggest different possible mechanisms, many of
      them are far distant from the primary physiological role of melatonin as a
      neurohormone. Conflicting studies are found on the role of melatonin in
      neurodegenerative diseases and cancer. In this article, we try to build and
      substantiate a neurobiological concept for the anticancer effects of melatonin.

PMID- 18090124
TI  - The role of adhesion molecules, alpha v beta 3, alpha v beta 5 and their ligands
      in the tumor cell and endothelial cell adhesion.
AB  - Tumor metastasis is a complex process involving the interaction between tumor
      cells and endothelial cells in which some adhesion molecules play an important
      role. It was our aim to investigate the role of the adhesion molecules, alpha v
      beta 3 and alpha v beta 5 and their ligands, developmental endothelial locus-1
      (Del-1) and L1, in tumor cell adhesion to endothelial cells in vitro. In this
      study, the expression and regulation of alpha v beta 3, alpha v beta 5 and
      intercellular adhesion molecule -1 on liver sinusoidal endothelial cells and
      liver cancer endothelial cells (T3A) were analyzed by real-time PCR and
      fluorescent-activated cell sorter. The expression and regulation of the integrin
      ligands, Del-1 and L1, in six tumor cell lines were analyzed by real-time PCR and
      western blot. We found the expressions of alpha v beta 3 and alpha v beta 5 were
      higher on T3A than that on liver sinusoidal endothelial cells, whereas expression
      of intercellular adhesion molecule-1 was lower on T3A than that on liver
      sinusoidal endothelial cells. After 24 h hypoxia, the expressions of alpha v beta
      3 and alpha v beta 5 were upregulated on T3A and liver sinusoidal endothelial
      cells; the expression of intercellular adhesion molecule-1 was increased on liver
      sinusoidal endothelial cells, but remained unchanged on T3A. Del-1 and L1
      expression levels were obviously diverse in various tumor cell lines and
      differentially modulated after 12 h hypoxia. The adhesion of tumor cells with Del
      1 and L1 expression was higher in T3A than that in liver sinusoidal endothelial
      cells, and was significantly increased under hypoxic conditions. Interestingly,
      the tumor cell adherence could be inhibited by antibodies against alpha v beta 5
      and alpha v beta 5, but not by an antibody against intercellular adhesion
      molecule-1. The adhesion of tumor cells without Del-1 and L1 expression was also
      higher on T3A than that on liver sinusoidal endothelial cells, but the adhesion
      could not be inhibited by antibodies against alpha v beta 5, alpha v beta 5 or
      intercellular adhesion molecule-1, suggesting that other receptors are involved.
      In conclusion, alpha v beta 5, alpha v beta 5 and their ligands Del-1 and L1 play
      an important role in the process of tumor cells moving from the original place.

PMID- 18090125
TI  - Inhibition by acetaminophen of neoplastic initiation elicited in rat liver by the
      DNA-reactive hepatocarcinogen N-acetyl-2-aminofluorene.
AB  - Acetaminophen, a monocyclic phenolic compound and analgesic, when fed at 8900
      p.p.m. in the diet, was reported to inhibit the hepatocarcinogenicity in rats of
      the aromatic amine proximate carcinogen N-hydroxy-N-acetyl-2-aminofluorene. To
      elucidate the mechanism(s) of this anticarcinogenicity, the present study
      examined whether acetaminophen at lower doses has the ability to inhibit the
      initiating effects in the rat liver of the precursor hepatocarcinogen N-acetyl-2
      aminofluorene. Male F344 rats were allocated to six groups, which were maintained
      under reverse light cycle conditions to assure acetaminophen ingestion at the
      time of N-acetyl-2-aminofluorene administration during the dark phase, which was
      imposed from 07.00 to 19.00 h. Group 1 served as vehicle control (0.5%
      carboxymethylcellulose) for N-acetyl-2-aminofluorene, which was administered
      intragastrically 3 days per week at 2.6 mg/kg for 8 weeks (group 4) to achieve
      initiation. Acetaminophen was given in the diet either alone at 2400 or 4800
      p.p.m. for 9 weeks (groups 2 and 3), or with N-acetyl-2-aminofluorene (groups 5
      and 6), starting 1 week before N-acetyl-2-aminofluorene administration.
      Acetaminophen blood levels were about 1 and 4 microg/ml at the two dietary
      concentrations. N-acetyl-2-aminofluorene induced hepatocellular preneoplastic
      lesions measured as hepatocellular altered foci expressing glutathione S
      transferase-P, reflecting initiation. Induced foci were reduced with
      administration of both concentrations of acetaminophen. Acetaminophen by itself
      produced no DNA adducts nor did it alter the high formation of N-acetyl-2
      aminofluorene-DNA adducts, about 200 in 10 nucleotides, measured by nucleotide
      postlabeling. Acetaminophen did not affect background liver cell proliferation,
      but significantly reduced N-acetyl-2-aminofluorene-induced increased
      proliferation measured by proliferating cell nuclear antigen immunostaining.
      Thus, acetaminophen effectively protected hepatocytes from the initiating effects
      of N-acetyl-2-aminofluorene, possibly through a cytoprotective effect resulting
      from slowing the rate of induced cell turnover.

PMID- 18090126
TI  - Which patients with colorectal cancer are followed up by general practitioners? A
      population-based study.
AB  - The aim of the study was to assess the contribution of general practitioners in
      the surveillance of colorectal cancer, and to examine characteristics and
      survival of patients with routine general practitioner follow-up. This French
      registry-based study included 389 patients diagnosed with first colorectal cancer
      in 1998 and free of disease at least 6 months after curative surgery. For each
      physician involved, medical records were thoroughly reviewed to collect
      information about the clinical examinations and follow-up tests prescribed within
      3 years after surgery or until death or detection of recurrence. Five-year vital
      status was obtained through registry records. The proportion of routine clinical
      examinations performed by general practitioners increased from 35% in the first
      year to 65% in the third year. Patients having undergone regular general
      practitioner routine examinations (> or =one examination every 6-month period)
      had significantly less advanced disease (odds ratio: 0.45; 95% confidence
      interval: 0.21-0.96), preoperative complications (odds ratio: 0.28; 95%
      confidence interval: 0.08-0.91) and routine examinations by
      gastroenterologists/oncologists (odds ratio: 0.37; 95% confidence interval: 0.14
      0.98) compared with those without general practitioner examinations. Routine
      general practitioner follow-up had no influence on 3 and 5-year survival. General
      practitioners detected significantly more recurrences than specialists in
      patients over 75 and in those presenting symptoms. French general practitioners
      are widely involved in the surveillance of patients with early-stage colorectal
      cancer, without any unfavourable impact on the patient's survival. Some
      suggestions exist that continuing education in oncology may increase the
      implication of general practitioners in colorectal cancer surveillance.

PMID- 18090127
TI  - Green tea and coffee intake and risk of pancreatic cancer in a large-scale,
      population-based cohort study in Japan (JPHC study).
AB  - Pancreatic cancer is one of the most aggressive and treatment-refractory
      malignancies in humans. The most effective means of reducing pancreatic cancer
      mortality may be primary prevention. Although laboratory studies have
      demonstrated that green tea possesses anticancer activities, results from
      epidemiological studies have failed to show a consistent cancer-preventive
      effect. In addition, there is a lingering concern that coffee mighty increase the
      risk of pancreatic cancer although the most recent epidemiological studies showed
      no overall association between coffee and risk. Here, we examined the association
      between the drinking of green tea or coffee and the risk of pancreatic cancer in
      a large population-based cohort study in Japan (JPHC study). In total, 102 137
      participants were followed for an average of 11 years through to the end of 2003.
      A total of 233 incident cases of pancreatic cancer were identified among 1 116
      945 person-years of follow-up. Overall, the risk of pancreatic cancer was not
      associated with either green tea or coffee intake in our population, although a
      reduced risk was apparent among men who drank at least three cups of coffee per
      day compared with those who did not drink any or only rarely drank coffee. In
      conclusion, our findings support the idea that green tea or coffee consumption
      does not have a substantial impact on pancreatic cancer risk in general.

PMID- 18090128
TI  - Ethnic ancestry and increased paternal age are risk factors for breast cancer
      before the age of 40 years.
AB  - To study the risk factors associated with breast cancer in women younger than 40
      years, a cohort study (The Jerusalem Perinatal Study) of 42 822 female offspring
      born in hospitals in West Jerusalem during 1964-1976 was carried out. Hazard
      ratios of potential parental and perinatal risk factors for early breast cancer
      were measured. The overall incidence of breast cancer was 5.2/100 000 person
      years. The highest incidence was found among Jewish women of West Asian ancestry
      (8.6/100 000 person-years), specifically those whose maternal grandfathers were
      born in Iraq, Iran or Afghanistan (9.5/100 000 person-years). Using Cox models we
      found independent risk factors for early breast cancer to be paternal age
      (relative risk/year=1.06, 95% confidence interval=1.02-1.10, P=0.005), and
      ancestry from Iraq/Iran/Afghanistan (relative risk=3.1, 95% confidence
      interval=1.50-6.52, P=0.002). The study confirms a previously observed effect of
      advanced paternal age on the occurrence of early breast cancer and identifies a
      novel population group at increased risk for the disease. The excess risk of
      early breast cancer associated with ancestry from Iraq, Iran and Afghanistan
      suggests involvement of genetic determinants, environmental exposures and/or
      lifestyle factors and mandates further investigation.

PMID- 18090129
TI  - A case-control study of cancer of the uterine cervix in Uganda.
AB  - As part of an epidemiological study of cancer in Uganda, we investigated social,
      sexual and reproductive factors in relation to the risk of cancer of the uterine
      cervix. Patients with all cancer types or with benign tumours were recruited from
      hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle
      factors and tested for antibodies against the human immunodeficiency virus-1
      (HIV). The case-control study reported here involves 702 HIV-seronegative women,
      343 of whom were diagnosed with cancer of the uterine cervix. Key findings were
      that the risk of cervical cancer increased linearly with the number of
      pregnancies [chi2(1)=44.7; P<0.0001]; a woman reporting having had 10 or more
      children had a roughly seven-fold increase in risk of the tumour as compared with
      women reporting fewer than four pregnancies (odds ratio=7.1; 95% confidence
      interval 3.8-13.2). The risk also varied inversely with age at first reported
      sexual intercourse [chi2(1)=8.4; P=0.004], perhaps reflecting an earlier age of
      infection with human papillomavirus, the main causal agent. These results are in
      line with those reported from studies in other countries.

PMID- 18090130
TI  - Promotion of cervical screening among nonattendees: a partial cost-effectiveness
      analysis.
AB  - Measures to increase attendance rate in cervical screening programmes have been
      suggested, but few have been evaluated in terms of value for money. The aim of
      this study was to describe the cost-effectiveness of a resource-intensive
      intervention to promote attendance at cervical screening among women with no
      registered cervical smear during the last 5 years. Among all 56 644 women (28-65
      years) in Kalmar County, January 2004, a total of 6565 women had no registered
      cervical smear during the last 5 years. From this population, 400 women were
      randomly selected to a study group and another 400 women to a control group. The
      intervention was composed of a variety of efforts intended to promote attendance
      at cervical screening. We included, for example, all costs for identifying the
      women, sending out invitation letters, making phone calls and helping to make
      arrangements. Data on registered cervical smears at follow-up were collected from
      a data register within 1 year. In the study group, 118 women had a registered
      cervical smear compared with 74 in the control group (P=0.000). In the study
      group, the cost per cervical smear taken was 66.87 euro compared with 16.63 euro
      in the ordinary screening programme. The incremental cost per additional
      registered cervical smear was calculated at 151.36 euro in an area with high
      coverage, efforts to promote attendance at cervical screening were related to
      high costs per extra cervical smear gained and is not considered as reasonable
      from a cost-effectiveness perspective.

PMID- 18090131
TI  - The cytological screening turned out effective also for adenocarcinoma: a
      population-based case-control study in Trento, Italy.
AB  - To evaluate the effectiveness of a cytological screening to prevent invasive
      cervical cancer in the province of Trento, a northern Italian area where a
      population-based cancer registry is active. The history of Pap test was evaluated
      through a case-control study in 61 population-based invasive cervical cancer
      patients, incident during 1995-2000, and in 244 age-matched (between 25 and 75
      years old) controls. Women who had at least one Pap test had a reduced risk of
      invasive carcinoma of 80% (odds ratio=0.20; 95% confidence intervals 0.10-0.40).
      The protection of a previous Pap test for both squamous cell carcinoma (odds
      ratio=0.23; 95% confidence intervals 0.09-0.58) and adenocarcinoma (odds
      ratio=0.24; 95% confidence intervals 0.07-0.78) was similar. The overall
      protective effect of the Pap test was not seen among younger women (<40 years).
      The protective effect of the Pap test seems to be stronger for shorter intervals.
      Our study confirms that Pap-test screening, particularly in middle-aged and older
      women, is an effective public health intervention with encouraging results also
      for the prevention of cervical adenocarcinoma.

PMID- 18090132
TI  - 15-Lipoxygenase-2 is differentially expressed in normal and neoplastic ovary.
AB  - Ovarian cancer is a major cause of lethality from gynecological malignancies, and
      there is a lack of reliable and specific serum markers for this disease.
      Eicosanoid-related enzymes have previously been implicated in the pathogenesis of
      various types of cancer, but little is known about the relevance of lipoxygenase
      isoforms in ovarian cancer and the results on cyclooxygenases are conflicting.
      For this study, we quantified the expression of eicosanoid-related enzymes
      (cyclooxygenase-1 and cyclooxygenase-2, 15-lipoxygenase-1 and lipoxygenase-2, 5
      lipoxygenase) in normal and malignant human ovarian tissue by real-time
      polymerase chain reaction and found a 22-fold elevated expression of 15
      lipoxygenase-2 in malignant specimens when compared with normal ovarian tissue
      (P=0.001). In ovarian carcinoma metastases, expression of the enzyme was also
      augmented (20-fold upregulation, P=0.004). For 15-lipoxygenase-1 and
      cyclooxygenase-2, we did not observe differential expression, but there was a
      trend for increased steady-state concentrations of cyclooxygenase-1 (P=0.1 for
      ovarian carcinoma, P=0.011 for metastases) and 5-lipoxygenase (P=0.1 for ovarian
      carcinoma, P=0.018 for metastases, respectively). These data indicate that
      expression of 15-lipoxygenase-2 mRNA is strongly augmented during ovarian
      carcinogenesis and that the enzyme may constitute a suitable candidate as a tumor
      marker.

PMID- 18090133
TI  - Analysis of nonresponse in the assessment of health-related quality of life of
      childhood cancer survivors.
AB  - The aim of this study was to compare the characteristics of respondents and
      nonrespondents in a survey of childhood cancer survivors recorded in the
      Childhood Cancer Registry of Piedmont and their current primary care general
      practitioners. Eligible subjects were identified from the Childhood Cancer
      Registry of Piedmont and the referring general practitioners were traced through
      the National Health Service. A postal questionnaire was sent both to childhood
      cancer survivors and to their general practitioners. Prevalence odds ratios were
      estimated for demographic and clinical characteristics in survivors and for
      demographic characteristics in general practitioners. A total of 1005 childhood
      cancer survivors and 857 general practitioners (132 of them had two or more
      cancer survivors in care) were included in the study. Completed questionnaires
      were obtained from 691 survivors (69%) and 615 general practitioners (72%). For
      survivors, the only associations with nonresponse were for age 35-44 years
      [prevalence odds ratio: 0.53 (95% confidence interval: 0.33-0.85)], being married
      [prevalence odds ratio: 1.45 (95% confidence interval: 0.96-2.18)] and diagnosis
      after 1977 [prevalence odds ratio: 0.66 (95% confidence interval: 0.42-1.03)].
      For general practitioners, the only associations were for male sex [prevalence
      odds ratio: 1.62 (95% confidence interval: 1.13-2.32)] and place of work outside
      of the city of Turin [prevalence odds ratio: 1.93 (95% confidence interval: 1.07
      3.47)]; furthermore associations were relatively weak. An association was also
      found between nonresponse in survivors and nonresponse in their general
      practitioners [prevalence odds ratio: 3.40 (95% confidence interval: 2.54-4.56)].
      In conclusion, apart from age, marital status and period of diagnosis, there were
      little differences between respondent and nonrespondents, for the considered
      clinical and demographical characteristics. Participation of survivors and their
      general practitioners correlated, suggesting that involvement of the general
      practitioners in the study may be a method to increase participation of survivors
      of childhood cancers.

PMID- 18090138
TI  - Patent foramen ovale and cryptogenic stroke.
AB  - Strokes are the leading cause of long-term, serious disability. A variety of
      identifiable risk factors exists for the development of a stroke. Individuals who
      had no definite and clearly identifiable cause for a stroke experience a
      cryptogenic stroke. The presence of a patent foramen ovale, a flaplike opening of
      the atrial septum between the septum primum and secundum, contributes to a 40% to
      56% incidence of a cryptogenic stroke. This article reviews the pathophysiology
      of a patent foramen ovale, the diagnostic tests, and nurse's awareness of the
      potential etiology of a stroke in a younger individual.

PMID- 18090139
TI  - Update on drug-eluting stents.
AB  - Coronary artery disease is the number 1 killer of Americans. There are many
      efforts underway to prevent and treat this life-threatening disease. One such
      treatment is the placement of drug-eluting stents. However, recent reports that
      show an increased risk of potentially life-threatening complications associated
      with drug-eluting stents have surfaced. This article provides a brief overview of
      research performed concerning the risks of drug-eluting stents.

PMID- 18090141
TI  - A personal reflection: humor--I'd rather laugh than cry.
AB  - This article examines the benefits of humor in both our personal and professional
      lives. Strategies to promote humor are also discussed.

PMID- 18090142
TI  - The problem of plagiarism.
AB  - Unfortunately, the frequency of plagiarism is increasing in the nursing
      profession. We are encouraged to write, especially those of us in academia, and
      we all live very active lives. Pressure to publish, especially when coupled with
      lack of time, can lead to plagiarism, whether inadvertent or not. This article
      will discuss the problem of plagiarism and provide tips on how to avoid it in
      your own work.

PMID- 18090143
TI  - Innovative solutions: my heart is a what?! Creativity in critical care education.
AB  - Nurses teach patients, families, and other healthcare providers. All of us teach
      our neighbors and communities. Choosing strategies for teaching essential content
      is the challenge we face every day. This article describes some innovative ways
      to share knowledge using creativity and imagination.

PMID- 18090144
TI  - Precepting student nurses in the intensive care unit.
AB  - Nurses in critical care units are often asked to precept a student nurse. To make
      this a valuable learning experience, careful planning should be done. The
      preceptor and the nursing faculty member need to collaborate to plan and carry
      out the nursing experience.

PMID- 18090145
TI  - Rapid response teams: do they make a difference?
AB  - Hundreds of lives are now being saved in hospitals across the country with the
      use of rapid response teams. These teams are composed of clinicians who bring
      critical care expertise to the patient bedside. The purpose of these teams is to
      assess and stabilize the patient, assist with communication among the
      interdisciplinary care providers, educate and support the staff caring for the
      patient, and assist with transfer of the patient if necessary. Research has shown
      that, with successful implementation of a rapid response team, the percent of
      codes and mortality rates decrease. The purpose of this study was to evaluate the
      effectiveness of implementing a rapid response team at 1 medical center. The
      results from the study demonstrated a decrease in the percent of codes outside
      the critical care units. However, it did not show a decrease in overall mortality
      rates for the patients. Data review will continue as we strive to improve our
      overall mortality rates while maintaining a decrease in the amount of codes.

PMID- 18090148
TI  - Guideline development and education to insure accurate and consistent pulmonary
      artery wedge pressure measurement by nurses in intensive care units.
AB  - A consistent pulmonary artery wedge pressure measurement is vital to insure that
      patients have the proper fluid balance and that the healthcare team obtain
      accurate information on the patients' ventricular function. This article
      discusses how guidelines for pulmonary artery wedge pressure measurement were
      developed and implemented at one facility. To implement and ensure that the
      guidelines were effective, nurses received a copy of guidelines for pulmonary
      artery wedge pressure measurement and they were posted in the intensive care
      unit. A pretest was completed before nurses were given the guidelines, and a
      posttest was completed after nurses reviewed the guidelines. This fast and simple
      method of education was found to increase nurses' knowledge of how to measure
      pulmonary artery wedge pressure. These results are encouraging and warrant
      extending the teaching techniques to other nurses caring for critically ill
      patients.

PMID- 18090149
TI  - Cardiopulmonary resuscitation: for any price?

PMID- 18090153
TI  - Optimizing methods for the diagnosis of pancreatic cancer.

PMID- 18090154
TI  - Caffeic acid phenethyl ester (CAPE) may be a promising adjuvant treatment in
      gastric cancer.

PMID- 18090155
TI  - Selective leukocyte apheresis for the treatment of inflammatory bowel disease.
AB  - The etiology of inflammatory bowel disease (IBD) is not completely understood,
      thus current therapies have been empirical and directed at treating symptoms
      rather than addressing the cause. In IBD, the overexpression of proinflammatory
      cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, interleukin-6,
      leads to a persistent intestinal inflammatory response that damages the
      intestinal mucosa. Recent advances in pharmacologic therapies that target
      specific cytokines, chemokines, and adhesion molecules have proved successful in
      alleviating symptoms for some patients. There are 2 selective adsorption
      apheresis devices that remove leukocytes from whole blood, which are currently
      available in Japan and Europe-the Cellsorba leukocytapheresis column and the
      Adacolumn adsorptive extracorporeal granulocyte/monocyte apheresis device. The
      purported mechanisms of action of these devices have been extensively reviewed
      and are believed to exert an immunomodulatory and/or anti-inflammatory effect on
      patients with systemic inflammatory disease. The clinical trials presented here
      indicate that selective leukocyte apheresis effectively removes activated
      granulocytes and monocytes/macrophages from peripheral blood while maintaining an
      excellent safety profile. Despite these findings, large controlled trials of
      selective leukocyte apheresis in the treatment of IBD are needed to determine the
      true efficacy of this approach.

PMID- 18090156
TI  - Satisfaction of the referring physician: a quality control study focusing on EUS.
AB  - INTRODUCTION: Utilization of endoscopic ultrasonography (EUS) is becoming more
      widespread. Largely in control of use of EUS, as a primary consumer of EUS, are
      the physicians who refer patients. This quality control study aimed to uncover
      remedial impediments to ideal utilization of EUS. METHODS: Two thousand patient
      EUS reports, all by one endoscopist, were screened. One hundred forty referring
      physicians were identified. One hundred of these physicians completed extensive
      feedback survey questionnaires. RESULTS: Overall satisfaction with EUS procedures
      was generally high. The level of satisfaction was comparable to satisfaction with
      gastroscopy procedures, both being significantly higher than for endoscopic
      retrograde cholongio-pancreatography. Sixty-nine percent of the physicians
      indicated their desire for more information regarding EUS, this being
      significantly higher among residents (vs. specialists). The open access system in
      current practice was seen as acceptable by less than half of physicians, both
      from the community and from within the hospital. Waiting time for EUS procedures
      and for biopsy results were rated as acceptable within the hospital, but more
      often as too long for outpatients. CONCLUSIONS: Overall satisfaction with EUS
      procedures is high. More information should be brought to the referring
      physicians, in print and lectures. Improving communication and interacting with
      endoscopist-initiated feedback led to improved feelings of teamwork, uncovered
      remedial weak points in the EUS service, and was thus found to be valuable.

PMID- 18090157
TI  - Predictive role of nuclear factor-kappaB activity in gastric cancer: a promising
      adjuvant approach with caffeic acid phenethyl ester.
AB  - BACKGROUND: The biologic significance of nuclear factor-kappaB (NF-kappaB)
      activation in human gastric cancer is unclear. We clarify the clinical
      significance of NF-kappaB activation and its relationship to Helicobacter pylori
      infection, a well-known pathogenesis of gastric cancer. Moreover, we examine the
      effects and underlying mechanisms induced by caffeic acid phenethyl ester (CAPE),
      an inhibitor of NF-kappaB, for gastric carcinoma. METHODS: NF-kappaB was located
      immunohistochemically in 90 human gastric cancer specimens and 50 nonmalignant
      gastric specimens. The correlations between NF-kappaB activation, pathologic
      staging, and H. pylori infection were analyzed. We also performed electrophoretic
      mobility gel shift assay, real-time reverse transcription polymerase chain
      reaction, and enzyme-linked immunosorbent assay to evaluate the responses of AGS
      (a gastric adenocarcinoma epithelial cell line) human gastric cancer cells
      subsequent to H. pylori infection or CAPE treatment. RESULTS: Nuclear expression
      of NF-kappaB was significantly more frequently observed in gastric cancer tissues
      than in nonmalignant gastric tissues (31% vs. 4%, P=0.0001). The activity of NF
      kappaB and the expressions of MMP-9, IL-1beta, and IL-8 in AGS cells were
      activated by H. pylori infection. However, the augmented responses could be
      significantly reversed by CAPE treatment. Moreover, in vitro studies showed that
      CAPE inhibits tumor growth and capacity for invasion. CONCLUSIONS: NF-kappaB
      activation is related to carcinogenesis, tumor aggression, and H. pylori
      infection with the increased expression of MMP-9, IL-1beta, and IL-8. Moreover,
      NF-kappaB inhibitors or anti-inflammatory agents such as CAPE might be new
      adjuvant agent against invasive gastric carcinoma.

PMID- 18090158
TI  - The addition of fiber and the use of continuous infusion decrease the incidence
      of diarrhea in elderly tube-fed patients in medical wards of a general regional
      hospital: a controlled clinical trial.
AB  - GOALS: To determine if feeds high in fiber continuously administered might
      minimize diarrhea. BACKGROUND: The addition of soluble fiber to enteral feedings
      has not consistently decreased diarrhea in controlled clinical trials, and the
      effect of the use of intermittent or continuous infusions on the rate of diarrhea
      is similarly controversial. STUDY: We studied 148 of 160 selected elderly well
      nourished patients with acute disease prohibiting oral intake in a controlled
      clinical trial in the setting of an internal medicine departments in a regional
      hospital who were divided into 4 groups and fed according to combinations of
      intermittent or continuous systems, with fiber-free or fiber rich formulas. The 5
      day rate of diarrhea was defined as 2 liquid stools or 3 or more semisolid or
      liquid bowel movements during a 24-hour period. Other outcome variables included
      mortality, hospital days, prolonged hospitalization (over 20 d), fever, and
      stools positive for Clostridium difficile cytotoxin A/B. RESULTS: The increased
      relative risk of the continuous/fiber-free, intermittent/fiber, and
      intermittent/fiber-free groups compared with the continuous/fiber group was 2.8
      [95% confidence interval (CI)=1.0-8.1], 2.5 (95% CI=0.9-7.1), and 5.0 (95% CI=1.9
      13.2), respectively. These findings were independent of age (>80 y), female sex,
      being treated with antibiotics for respiratory or urinary infections, receiving
      respiratory support, or being fully conscious. There were no significant
      differences in the other outcomes. CONCLUSIONS: We conclude that in elderly well
      nourished hospitalized patients with acute diseases prohibiting oral intake,
      continuous and closed enteral feedings with the addition of fiber is effective in
      reducing the rate of diarrhea.

PMID- 18090159
TI  - Kras mutation analysis of fine needle aspirate under EUS guidance facilitates
      risk stratification of patients with pancreatic mass.
AB  - OBJECTIVES: The accuracy of endoscopic ultrasound-fine needle aspiration cytology
      (EUS-FNAC) for the diagnosis of pancreatic cancer is suboptimal. Mutational
      activation of the kras oncogene is almost universally present in pancreatic
      cancer tissue. We, therefore, investigated if analysis for mutant kras gene in
      the EUS-FNAC aspirates supplements cytopathology for the diagnosis of pancreatic
      adenocarcinoma (PAC). METHODS: EUS-FNAC specimens obtained from 74 patients with
      pancreatic masses were analyzed for the presence of kras mutation on codon 12
      using polymerase chain reaction-restriction fragment length polymorphism and MvaI
      restriction enzyme. Definitive diagnosis was based on surgical pathology or long
      term follow-up (median 27.8 mo); 57 patients had PAC, 11 patient's chronic
      pancreatitis, and 9 patient's nonfunctioning neuroendocrine tumors. RESULTS:
      Analysis of mutant kras gene in addition to cytopathology allowed the detection
      of PAC in 4 additional patients as compared with cytopathology alone.
      Cytopathology and kras mutant analysis were negative for PAC in 17 patients of
      whom 6 patients (35%) had PAC. The respective sensitivity (90.9% vs. 82.5%),
      specificity (47.6% vs. 97.9%), positive predictive value (89.5% vs. 83.8%),
      negative predictive value (98.1% vs. 94.1%), accuracy (89.2% vs. 58.8%) of
      cytopathology plus kras mutation versus cytopathology were numerically superior
      but did not reach statistical significance. CONCLUSIONS: Analysis for the
      presence of mutant kras gene supplements conventional cytopathology for the
      diagnosis of PAC even without a cytopathologist in attendance and using only 3
      needle passes. Among patients with negative cytopathology, the presence of kras
      mutation represents pancreatic cancer while the absence of kras mutation
      increases the possibility of benign lesion.

PMID- 18090160
TI  - Endoscopic and surgical therapy for intrahepatic cholangiocarcinoma in the united
      states: a population-based study.
AB  - BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly fatal disease with
      limited therapeutic options. The determinants, trends, and outcomes of different
      therapies for ICC are largely unknown in the United States. METHODS: Using data
      from the Surveillance, Epidemiology, and End-Results-(SEER) Medicare database, we
      compared ICC patients receiving different therapies between 1992 and 1999.
      Univariate and multivariate analyses were performed and adjusted odds ratios
      (AORs) were calculated. Hazard ratios were calculated for the survival analysis.
      RESULTS: Eight hundred sixty-two cases were included. The mean age at diagnosis
      was 77.9 years (SD=7.1). Only 6.3% received surgical resection, 65.5% received
      palliative interventions (16.1% surgical, 44.0% endoscopic), 24.4% received only
      chemo or radiation therapy whereas 3.8% did not receive any treatment. The median
      survival was 708 days [95% confidence interval (CI): 458-945] for surgical
      resection, 227 days (95% CI: 182-294) for surgical palliation, and 123 days (95%
      CI: 108-148) for endoscopic palliation. Patients receiving surgical resection
      were younger (AOR=5.6, 95% CI: 2.9-11.1), more likely to be diagnosed later in
      the study period (AOR=2.2, 95% CI: 1.1-4.2), and had better mortality (hazard
      ratio=0.3, 95% CI: 0.2-0.4). Patients receiving surgical palliation were younger
      (AOR=1.6, 95% CI: 1.1-2.3), more likely to be diagnosed in the early time period
      (AOR=1.5, 95% CI: 1.1-2.2), and had similar mortality to those receiving
      endoscopic palliation. CONCLUSIONS: Only a minority of patients with ICC receives
      potentially curative therapy. Young age is the strongest predictor of receiving
      potentially curative treatment. Older patients and those diagnosed in recent time
      periods are more likely to receive endoscopic palliation. Surgical resection was
      associated with improved survival. There was no difference in survival between
      surgical and endoscopic palliation.

PMID- 18090161
TI  - Liver enzymes and histology in obese patients with obstructive sleep apnea.
AB  - BACKGROUND AND AIMS: Recent studies have shown an association between obstructive
      sleep apnea (OSA) and elevated liver enzymes in patients with nonalcoholic fatty
      liver disease (NAFLD). The aim of the current study was to compare biochemical
      and histologic findings in patients with NAFLD as a function of OSA status.
      METHODS: Subjects consisted of 85 patients who had a sleep study followed by a
      liver biopsy performed at the time of obesity surgery. The diagnosis of OSA was
      based on an apnea hypopnea index of >/=15. Demographic and laboratory data were
      collected retrospectively. Liver biopsies were systematically evaluated for
      features of NAFLD including degree of steatosis, inflammation, and fibrosis.
      RESULTS: All but one patient had histologic evidence of NAFLD and 51% of the
      study population had OSA. A higher proportion of patients with OSA had elevated
      alanine aminotransferase levels (13/39) compared with those without OSA (3/34)
      (P=0.01). Only 19% of subjects had fibrosis on liver biopsy and still fewer (5%)
      had bridging fibrosis or cirrhosis. There was a trend toward a higher prevalence
      of OSA in patients with evidence of progressive liver disease, as indicated by
      inflammation plus fibrosis (11/15), compared with those with inflammation alone
      (22/48) (P=0.06). CONCLUSIONS: In obese patients with NAFLD, OSA was associated
      with elevated alanine aminotransferase levels and a trend toward histologic
      evidence of progressive liver disease.

PMID- 18090162
TI  - Predictors of mortality in hepatic encephalopathy in acute and chronic liver
      disease: a preliminary observation.
AB  - BACKGROUND: Several scoring systems are available to predict the outcome of liver
      cell failure. Scarce information is available on predictors in hepatic
      encephalopathy. OBJECTIVES: To study clinical and biochemical variables that
      would predict the outcome in hepatic encephalopathy. METHODS: Fifty consecutive
      patients with hepatic encephalopathy were included in the study. Variables
      included clinical and biochemical parameters, discriminant function, QTc interval
      and the need for ventilator support. Child-Pugh's Turcotte score and Mayo Clinic
      model for end-stage liver disease scores were calculated at admission. Patients
      were followed up until discharge or death. Logistic regression analysis was
      computed with the variables that predicted a favorable outcome. RESULTS: Chronic
      liver disease precipitated hepatic encephalopathy in 39 patients (group 1) and
      encephalopathy followed acute liver disease in 11 patients (group 2). In group 1,
      high serum bilirubin (P<0.001), prolonged QTc interval (P<0.05) and requirement
      for support systems (P<0.003) predicted a poor outcome. In group 2, higher grades
      of encephalopathy (P<0.04) and native drug therapy (P<0.007), high serum
      bilirubin (P<0.05), requirement for support systems (P<0.02) predicted a poor
      outcome. Mayo Clinic model for end-stage liver disease and discriminant function
      in both groups and Child-Pugh-Turcotte's score in group 1 did not predict the
      outcome. Logistic regression identified serum bilirubin in group 1 (OR 8.55,
      P=0.012) and native drug therapy in group 2 (odds ratio 3.85, P=0.05) as
      independent poor risk factors. CONCLUSIONS: High serum bilirubin values in
      chronic liver disease and native drug therapy in acute liver cell failure are
      simple parameters that would predict a poor outcome in patients with hepatic
      encephalopathy.

PMID- 18090163
TI  - Compliance with referral for hepatitis C evaluation among veterans.
AB  - GOALS: The goals of this study were to quantify the rate and to identify
      predictors of compliance with outpatient hepatitis C evaluation. BACKGROUND:
      Challenges in hepatitis C management include patient compliance with multiple
      clinic visits, laboratory tests, and radiologic studies throughout the management
      of hepatitis C. However, the success of hepatitis C management begins with the
      patient's compliance with referral for hepatitis C evaluation. STUDY: The
      administrative databases and medical records of patients who were newly referred
      to the Durham Veterans Affairs Medical Center for hepatitis C evaluation between
      2002 and 2004 were reviewed. RESULTS: A total of 376 veterans were identified as
      being newly referred to the Durham Veterans Affairs Medical Center
      gastroenterology and liver clinics for hepatitis C evaluation. The mean age of
      referred patients was 51.2+/-6.1 years, and 94.7% were men. The majority of
      patients (87%) were compliant with referral for hepatitis C evaluation. In
      multivariable logistic regression adjusting for age, race, marital status,
      history of psychiatric disease, history of substance abuse, origin of referral,
      and wait time, keeping other outpatient appointments was a significant predictor
      of compliance with referral for hepatitis C evaluation (odds ratio 6.00; 95%
      confidence interval 1.52, 23.67). CONCLUSIONS: Veterans have a high rate of
      compliance with referral for hepatitis C evaluation, and their compliance is
      likely reflective of their motivation to maintain general health care. Future
      studies assessing other factors, such as patient educational level and
      socioeconomic status, may help to elucidate more fully the factors impacting
      compliance with hepatitis C management.

PMID- 18090164
TI  - Efficacy of rifaximin and vancomycin combination therapy in a patient with
      refractory Clostridium difficile-associated diarrhea.

PMID- 18090165
TI  - Successful treatment of acute occlusion in superior mesenteric artery of an
      elderly man by thrombus aspiration.

PMID- 18090166
TI  - Signet cell gastric adenocarcinoma presenting as a sister Joseph nodule.

PMID- 18090167
TI  - Perceptions of a 24-hour visiting policy in the intensive care unit.
AB  - OBJECTIVE: To examine perceptions by intensive care unit (ICU) workers of
      unrestricted visitation, to measure visiting times, and to determine prevalence
      of symptoms of anxiety and depression in family members. DESIGN: Observational,
      prospective, single-center cohort. SETTING: Medical-surgical ICU in a 460-bed
      tertiary-care hospital. PATIENTS: Two hundred nine consecutive patients
      hospitalized >3 days were studied over the first 5 ICU days. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Characteristics of patients (n = 209), families (n
      = 149), and ICU workers (n = 43) were collected. ICU workers reported their
      perceptions of unrestricted visitation, and family members completed the Hospital
      Anxiety and Depression Scale. Daily severity scores (Simplified Acute Physiology
      Score II and Logistic Organ Failure) and a workload score (Nine Equivalents of
      Nursing Manpower) were computed. Maximum median visit length was 120 mins per
      patient per day and occurred on days 4 and 5. No correlations were found among
      severity of illness, workload, and visit length. For 115 patients, both nurse and
      physician questionnaires were available; although several differences were noted,
      neither nurses nor physicians perceived open visitation as disrupting patient
      care. The median rating for delay in organizing care was "never" for physicians
      and "occasionally" for nurses. Nurses perceived more disorganization of care than
      physicians (p = .008). Compared with nurses, the physicians reported greater
      family trust (p = .0023), more family stress (p = .047), and greater unease when
      examining the patient (p = .02). The Hospital Anxiety and Depression Scale
      indicated symptoms of anxiety in 73 (49%) family members and depression in 44
      (29.5%). CONCLUSIONS: The 24-hr visitation policy was perceived favorably by
      families. It induced only moderate discomfort among ICU workers, due to the
      potential for care interruption, in particular for nurses.

PMID- 18090168
TI  - Informed consent in the critically ill: a two-step approach incorporating
      delirium screening.
AB  - OBJECTIVES: Sedation-agitation and delirium are common in critically ill patients
      and may be important barriers to informed consent. We describe a two-step process
      for informed consent and evaluate the natural history of patients' competency by
      repeated application of this process during their hospitalization. DESIGN:
      Observational study. SETTING: Nine intensive care units (ICUs) in three teaching
      hospitals in Baltimore, MD. PATIENTS: One hundred fifty patients with acute lung
      injury. INTERVENTIONS: Two-step process involving objective evaluation with
      Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Method for the
      Intensive Care Unit (CAM-ICU) (step 1), followed by traditional assessment for
      competency (step 2) in those patients passing step 1. MEASUREMENTS AND MAIN
      RESULTS: RASS and CAM-ICU assessments (during ICU stay, at consent and hospital
      discharge); cumulative proportion of patients providing consent at extubation and
      at ICU and hospital discharge. Of 150 patients, 86 (57%) survived and 77 (90% of
      survivors) provided consent. Patients were delirious/deeply sedated in 89% of
      daily assessments during mechanical ventilation. By extubation, 31 (44%) patients
      passed step 1 and 8 (11%) passed step 2 and were consented. By ICU and hospital
      discharge, these numbers were 50 (58%) and 18 (21%), and 81 (94%) and 67 (78%),
      respectively. The median (interquartile range) time to patient consent after
      acute lung injury diagnosis was 15 (9-28) days. CONCLUSIONS: More than three
      fourths of critically ill patients are unable to provide informed consent
      throughout their ICU stay, even after extubation. Sedation-agitation and delirium
      are common barriers to consent. A two-step consent process, using validated
      instruments for sedation-agitation and delirium, provides a means of rapidly
      screening critically ill patients before a more detailed traditional assessment
      of competency is conducted.

PMID- 18090170
TI  - Relieving suffering or intentionally hastening death: where do you draw the line?
AB  - OBJECTIVE: End-of-life practices vary worldwide. The objective was to demonstrate
      that there is no clear-cut distinction between treatments administered to relieve
      pain and suffering and those intended to shorten the dying process. DESIGN:
      Secondary analysis of a prospective, observational study. SETTING: Thirty-seven
      intensive care units in 17 European countries. PATIENTS: Consecutive patients
      dying or with any limitation of therapy. INTERVENTIONS: Evaluation of the type of
      end-of-life category; dates and times of intensive care unit admission, death, or
      discharge; and decisions to limit therapy, medication, and doses used for active
      shortening of the dying process and the intent of the doctors prescribing the
      medication. MEASUREMENTS AND MAIN RESULTS: Limitation of life-sustaining therapy
      occurred in 3,086 (72.6%) of 4,248 patients, and 94 (2.2%) underwent active
      shortening of the dying process. Medication for active shortening of the dying
      process included administration of opiates (morphine to 71 patients) or
      benzodiazepines (diazepam to 54 patients) alone or in combination. The median
      dosage for morphine was 25.0 mg/hr and for diazepam 20.8 mg/hr. Doses of opiates
      and benzodiazepines were no higher than mean doses used with withdrawal in
      previous studies in 20 of 66 patients and were within the ranges of doses used in
      all but one patient. Doctors considered that medications for active shortening of
      the dying process definitely led to the patient's death in 72 patients (77%),
      probably led to the patient's death in 11 (12%), and were unlikely to have led to
      death in 11 (12%) patients. CONCLUSIONS: There is a gray area in end-of-life care
      between treatments administered to relieve pain and suffering and those intended
      to shorten the dying process.

PMID- 18090169
TI  - N-acetylcysteine for prevention of acute renal failure in patients with chronic
      renal insufficiency undergoing cardiac surgery: a prospective, randomized,
      clinical trial.
AB  - OBJECTIVE: To assess the preventive effect of the antioxidant N-acetylcysteine on
      postoperative acute renal failure in patients with renal insufficiency undergoing
      cardiac surgery. DESIGN: Randomized, placebo-controlled, prospective study.
      SETTING: University cardiology center. PATIENTS: Two hundred fifty-four
      consecutive patients with chronic renal insufficiency (estimated creatinine
      clearance < or = 60 mL/min) undergoing elective cardiac surgery. INTERVENTIONS:
      Patients were randomized to receive N-acetylcysteine (n = 129) or placebo (n =
      125). Patients of the N-acetylcysteine group received four boluses of intravenous
      N-acetylcysteine (1200 mg every 12 hrs, starting immediately before cardiac
      surgery). MEASUREMENTS AND MAIN RESULTS: The incidence of postoperative acute
      renal failure (> 25% increase in serum creatinine from baseline) and the in
      hospital clinical course were evaluated. Acute renal failure occurred in 46% of
      patients and was associated with increased in-hospital mortality (7% vs. 0.7%; p
      = .024). It occurred in 52% of control patients and 40% of N-acetylcysteine
      treated patients (p = .06). In-hospital mortality and need for renal replacement
      therapy were not affected by N-acetylcysteine, but a lower percentage of N
      acetylcysteine-treated patients required mechanical ventilation prolonged for >
      48 hrs (3% vs. 18%; p < .001) and had an intensive care unit stay > 4 days (13%
      vs. 33%; p < .001). CONCLUSIONS: Intravenous administration of N-acetylcysteine
      does not clearly prevent postoperative acute renal failure in patients with renal
      insufficiency undergoing cardiac surgery.

PMID- 18090176
TI  - An event-specific analysis of condom breakage among African American men at risk
      of HIV acquisition.
AB  - BACKGROUND: African American men are at high risk of human immunodeficiency virus
      acquisition. Condom breakage is an understudied aspect of their sexual protective
      behavior. This study identified user errors leading to condom breakage using an
      event-specific analysis among young African American men newly diagnosed with a
      sexually transmitted disease (STD). METHODS: Recruitment occurred in a publicly
      funded STD clinic located in a metropolitan area of the Southern United States.
      Of 296 African American men screened as eligible, 271 (91.5%) agreed to
      participate. Men completed a self-administered questionnaire. Men reporting
      condom use with men were excluded from the analysis, leaving an analytic sample
      of 264 men. The recall period was for the last time men used condoms for penile
      vaginal sex (within the past 3 months). RESULTS: More than one-fifth (21.2%)
      reported condom breakage. Each year of advancing age decreased the odds of
      breakage by 10% [adjusted odds ratio (AOR) = 0.90, 95% confidence interval (CI) =
      0.81-0.99, P = 0.028]. Men who had used an oil-based lubricant were more than 3
      times as likely to report breakage (AOR = 3.21, 95% CI = 1.48-7.00, P = 0.003)
      and those who completely unrolled the condom before putting it on were also about
      3 times more likely to report breakage (AOR = 3.34, 95% CI = 1.76-6.50, P =
      0.0001). The breakage rate for men indicating both errors, i.e., use of an oil
      based lubricant and unrolling the condom before application, was 54.5% compared
      with 33.3% among those indicated either error, and 12.8% among those indicating
      neither error. Attributable risk for the 2 errors combined was 39%. CONCLUSIONS:
      Condom breakage among this sample of men at high risk for human immunodeficiency
      virus infection was common. This problem could be mitigated by counseling men to
      avoid the use of oil-based lubricants and by teaching them basic condom
      application skills.

PMID- 18090177
TI  - Receipt of HIV and STD testing services during routine general medical or
      gynecological examinations: variations by patient sexual risk behaviors.
AB  - OBJECTIVE: Clinical practice guidelines in the United States recommend screening
      patients who report high-risk sexual behaviors (HRSB) for human immunodeficiency
      virus (HIV) and selected sexually transmitted diseases (STDs). The objective of
      this study was to estimate HIV and STD diagnostic and testing practices during
      routine general medical examinations (RGME) or gynecological examinations (GYNE)
      of patients by their reported HRSB status. METHODS: We analyzed medical claims
      data from commercially-insured patients in the United States who sought care
      during 2000-2003. International Classification of Disease-9 (ICD-9) diagnostic
      and Current Procedural Terminology procedural codes were used to identify claims
      for HRSB, RGME or GYNE, HIV and STD diagnoses, and HIV and STD tests. RESULTS: Of
      4296 patients aged 15 to 54 years during RGME or GYNE, almost none had ICD-9
      codes for HIV, syphilis, Chlamydia trachomatis (CT) or Neisseria gonorrhoeae (NG)
      infection. Patients with claims for HRSB were significantly more likely than
      patients without a claim for HRSB to be tested for HIV, syphilis, CT, and NG.
      Among patients with HRSB-RGME, men were significantly more likely to be tested
      for HIV (79.3% vs. 38.8%) and syphilis (39.1% vs. 27.6%) and less likely to be
      tested for CT (20.7% vs. 56.9%) and NG (20.7% vs. 50.9%) than were women.
      CONCLUSIONS: A large proportion of patients with HRSB at RGME or GYNE did not
      receive HIV and STD tests. Interventions to increase HIV and STD testing of
      patients at visits with claims for HRSB are needed to enhance guideline
      adherence.

PMID- 18090178
TI  - Prevalence and predictors of sexually transmitted infection among newly
      incarcerated females.
AB  - OBJECTIVES: To examine demographic and behavioral characteristics in incarcerated
      women to determine which characteristics are associated with prevalent sexually
      transmitted infections (STIs). STUDY DESIGN: A cross-sectional analysis of data
      of 205 women entering jail in Rhode Island was performed as part of a study
      evaluating a family planning program. Women were recruited near time of
      commitment, and inclusion was limited to women at risk for an unplanned
      pregnancy. Incarcerated women were interviewed by a research assistant for
      demographic information, psychosocial and behavioral characteristics. Self
      collected vaginal swabs were tested for STIs, including Neisseria gonorrhoeae and
      Chlamydia trachomatis by polymerase chain reaction and Trichomonas vaginalis by
      InPouch culture. Relative risks (RRs) were estimated using Poisson regression.
      RESULTS: Sixty-eight of 205 patients tested positive for an STI [33%; 95%
      confidence interval (CI) 27-40%]. Forty-five patients (26%) tested positive for
      T. vaginalis, 27 (14%) were positive for C. trachomatis, and 21 (11%) were
      positive for N. gonorrhoeae. On bivariate analysis, 6 or more sexual partners in
      the last year (RR 1.84; 95% CI 1.01-3.36), exchanging sex for drugs/money (RR
      1.65; 95% CI 1.01-2.69), and homelessness (RR 1.82; 95% CI 1.07-3.09) were
      associated with STI. After adjustment for age, race/ethnicity, education, and
      other covariates, none of the factors was significantly associated with STI.
      CONCLUSIONS: The prevalence of STI in this jail population is high. Incarceration
      represents a unique opportunity to evaluate and treat this underserved
      population. Predictors of infection are limited and infection is common;
      therefore, routine screening should be considered in this population.

PMID- 18090179
TI  - Core components of cardiac rehabilitation/secondary prevention programs: 2007
      update.

PMID- 18090180
TI  - Cardiovascular risk factors and metabolic syndrome in alcohol- and nicotine
      dependent men and women.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Cardiovascular disease (CVD) is a leading
      cause of mortality among alcohol-dependent people; however, minimal data exist on
      the CVD risk factor profile in this high-risk population. The purpose of this
      study was to examine the prevalence and clustering of traditional and novel CVD
      risk factors, including components of the metabolic syndrome, in nicotine- and
      alcohol-dependent adults. SUBJECTS AND METHODS: Participants (n = 46; 61% men;
      87% white), who were a consecutive series of eligible adults (19-56 years of age;
      mean, 34.8 +/- 1.4 years; Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition-classified alcoholic; abstinent for <or=7 days), were assessed on
      entry to a residential drug treatment facility. Cardiovascular disease risk
      factors were measured using standardized protocols and interview-administered,
      self-report inventories adapted from epidemiological studies. Dyslipidemia and
      metabolic syndrome were identified using Adult Treatment Panel III criteria;
      hypertension was classified by the Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of High Blood Pressure criteria. Enzymatic,
      colorimetric, and immunochemiluminometric techniques were used to measure plasma
      lipids, homocysteine, and high-sensitivity C-reactive protein, respectively.
      RESULTS AND CONCLUSIONS: Dyslipidemia was identified in 74% of participants; 54%
      were overweight or obese (body mass index, >or=25 kg/m2); 61% were physically
      inactive (<1,000 kcal/wk); and 61% had some form of hypertension. In addition,
      54% had increased homocysteine values; high-sensitivity C-reactive protein was
      elevated in 28%; and 22% of the participants met criteria for metabolic syndrome.
      In this study of the CVD risk profile among alcoholics, subjects were found to
      have an average of 3 CVD risk factors in addition to cigarette smoking. This
      prevalence and clustering of potentially modifiable risk factors in young,
      nicotine-dependent alcoholics indicate the need for aggressive risk reduction
      focused on prevention of CVD.

PMID- 18090181
TI  - Correlation of ankle-brachial index values with carotid disease, coronary
      disease, and cardiovascular risk factors in women.
AB  - BACKGROUND: Recent studies indicate that the use of ankle-brachial index (ABI)
      measurements helps identify patients with peripheral arterial disease. Previous
      research also reveals a relationship between peripheral arterial disease and
      higher incidence of cardiac mortality and morbidity. PURPOSE: The purpose of this
      study was to investigate the correlation of a low ABI (<0.90 mm Hg) with coronary
      artery disease, diabetes, hypercholesterolemia, body mass index greater than 25,
      a sedentary lifestyle, smoking, and carotid artery disease. METHODS: A
      descriptive correlational design was used to study a population (N = 810) of
      fairly healthy women who self-selected to undergo cardiovascular screening that
      they paid for out of pocket. Cardiac disease and most of the data on risk factors
      were obtained using questionnaires. Carotid artery stenosis was determined by
      ultrasound. Hypotheses were tested using chi2 and independent t test. RESULTS: A
      statistically significant relationship was found between a low ABI and the
      presence of moderate to severe carotid artery stenosis (chi2 = 5.90, P = .015). A
      low ABI (<0.90 mm Hg) was not significantly related to cardiac disease (chi2 =
      0.83, P = .362), diabetes (chi2 = 1.82, P = .177), hypercholesterolemia (chi2 =
      0.01, P = .930), claudication (chi2 = 2.06, P = .151), physical activity (chi2 =
      1.17, P = .884), or body mass index (t = 1.12, P = .270). CONCLUSION: The
      significant relationship between low ABI and carotid artery stenosis illustrates
      that atherosclerosis occurs in multiple arterial beds simultaneously. The lack of
      association between ABI and the other variables probably reflects the self-report
      nature of the data collected on these variables. Ankle-brachial index
      measurements may be useful in future research as a tool for early recognition of
      cardiovascular disease.

PMID- 18090182
TI  - The association of low birth weight and physiological risk factors of
      hypertension in African American adolescents.
AB  - Low birth weight (LBW) has been associated with increased blood pressure and the
      development of cardiovascular disease including hypertension. Elevated blood
      pressure, cortisol, and hyperresponsiveness during physiologic stress may
      function as hypertension biological markers. We examined the association of blood
      pressure and cortisol levels during induced physiologic stress with LBW in an
      African American adolescent population (n = 106). METHODS AND RESULTS: Birth
      weight was obtained from parents. Blood pressure and cortisol levels were
      measured at rest and in response to an induced physiological stressor. Compared
      with normal birth weight group (n = 73), the LBW group (n = 33) demonstrated
      elevated (+4 mm Hg) diastolic pressure (P = .002) and cortisol
      hyperresponsiveness (P = .05). Seventy-nine percent of LBW adolescents had
      elevated blood pressure and/or cardiovascular reactivity (P = .04), and 39% had
      elevated blood pressures. CONCLUSIONS: Low birth weight African American
      adolescents demonstrated physiological risk factors for hypertension, and these
      findings add support to the association between LBW and the development of
      hypertension.

PMID- 18090184
TI  - Progress in prevention: communicating health information to our patients: the
      tower of Babel?

PMID- 18090185
TI  - Review of the methods to prevent femoral arteriotomy complications and contrast
      nephropathy in patients undergoing cardiac catheterization: cardiac
      catheterization and care approaches in Turkey.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: There are different care and treatment
      approaches to prevent femoral arteriotomy complications and contrast nephropathy
      in patients undergoing cardiac catheterization. The purpose of our study was to
      identify approaches widely used in Turkey to prevent femoral arteriotomy
      complications and contrast nephropathy in patients undergoing cardiac
      catheterization. MATERIALS AND METHODS: The study was a descriptive study. A
      questionnaire was mailed to 36 university medical faculty hospitals that have
      active interventional cardiology units. Twenty-nine universities (80.5%)
      responded. RESULTS AND CONCLUSIONS: In general in Turkey, only manual pressure is
      used to achieve initial hemostasis at the femoral insertion site, with a pressure
      dressing and sandbag added to maintain hemostasis. Arterial closure devices are
      rarely used. In general, after the procedure, patients are required to lie flat
      with, at most, a 15- to 30-degree elevation during bed rest. To prevent contrast
      nephropathy in patients at risk, intravenous saline solutions are started before
      the procedure and continued afterward. In other patients, only oral fluid
      replacement is used. Traditional approaches in the management of femoral artery
      insertion site continue, and practices used in the prevention of contrast
      nephropathy are similar to current practices.

PMID- 18090186
TI  - Acute myocardial infarction patients' information needs over the course of
      treatment and recovery.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Healthcare guidelines promote including
      patients in healthcare decision making to optimize treatment and recovery.
      However, prior research varies widely in the clinical context and
      conceptualization of patient involvement. The current study focuses on describing
      cardiac patients' preferences for involvement in decision making in the context
      of the myocardial infarction event continuum. SUBJECTS AND METHODS: Focus groups
      were conducted with 19 patients who had recently experienced a myocardial
      infarction and received care at a regional facility in the Midwest. Data were
      transcribed and analyzed qualitatively to identify themes related to patient's
      decision-making experiences. RESULTS AND CONCLUSIONS: Both the role of the
      patient in decision making and information needs change as the patient progresses
      from the acute event to recovery. However, this change seems to be curvilinear,
      rather than linear. To maximize outcomes, clinicians must assess preferences and
      increase awareness of evolving information needs throughout the myocardial
      infarction clinical situation.

PMID- 18090187
TI  - Premedication for cardiac catheterization and percutaneous coronary intervention:
      does it increase vascular access site complications?
AB  - BACKGROUND: The aim of the study was to determine whether premedication with oral
      diazepam (5-10 mg) before coronary angiography or percutaneous coronary
      intervention was associated with an increase in access site related
      complications. We also aimed to determine the effect on patient's perception of
      anxiety and pain. METHODS: A total of 760 consecutive patients scheduled to
      undergo either cardiac catheterization or percutaneous coronary intervention were
      randomized to either premedication with diazepam 5-10 mg 30 to 60 minutes prior
      to procedures (n = 379) or no premedication (n = 381). Administration of
      intravenous midazolam during the procedures was permitted and was at the
      operator's discretion. The primary end point of the study was a composite of
      hematoma (>or=3 cm), pseudoaneurysm (requiring surgical repair), arterial
      bleeding (requiring further compression), and vasovagal events. Secondary end
      points included the patient's perception of pain and anxiety (n = 144). RESULTS:
      Hematomas (17% vs 15%, P = .41), pseudoaneurysm (0.3% vs 0%, P = .31), arterial
      bleeding (3.4% vs 4.2%, P = .58), vasovagals (4% vs 3%, P = .32), and the
      combined primary end point (25% vs 22%, P = .145) were similar in the
      premedication and no premedication groups. There was also no difference in the
      number of patients experiencing periprocedural anxiety (36% vs 37%, P = .862).
      However, those premedicated with diazepam were significantly less likely to
      report periprocedural pain (32% vs 53%, P = .0114). CONCLUSIONS: Treatment with
      oral diazepam prior to cardiac catheterization and percutaneous coronary
      intervention does not alter rates of access site complications or anxiety, but
      does reduce periprocedural pain.

PMID- 18090188
TI  - Partner quality of life in the antiarrhythmics versus implantable defibrillators
      trial.
AB  - BACKGROUND AND OBJECTIVE: The quality of life (QOL) of patients with ventricular
      dysrhythmias is well studied, but less is known about the QOL of their partners.
      This study describes the QOL of partners of patients with serious ventricular
      dysrhythmias enrolled in the Antiarrhythmics Versus Implantable Defibrillators
      trial. SUBJECTS AND METHODS: A convenience sample of 124 partners of patients
      randomized to antiarrhythmic drugs (n = 59) or an implantable cardioverter
      defibrillator (n = 65) in the Antiarrhythmics versus Implantable Defibrillators
      trial was obtained. The Short Form-36 and Quality of Life Index were assessed at
      baseline (postrandomization) and at 3-, 6-, and 12-month follow-up. RESULTS AND
      CONCLUSIONS: The mean age of the partners was 62 years. Most were white and
      female. Their mean Short Form-36 scores were comparable to a normative age group.
      Partner and participant mean Short Form-36 and Quality of Life Index scores
      correlated modestly (range 0.25-0.36). The physical summary scores of partners
      using the Short Form-36 declined over time, whereas their mental summary scores
      remained stable. Partner concerns related to death, dysrhythmia recurrence, and
      the impact of dysrhythmias on enjoyment of life lessened from baseline to 12
      months. Concern about implantable cardioverter defibrillator function remained
      stable over time. Although the sample size of this study was relatively small and
      limited by missing data for some assessments, it is the largest prospective study
      of QOL in partners of patients with serious dysrhythmias. The results offer a
      foundation for future research of the partners of patients with serious
      dysrhythmias in terms of identifying their needs, offering support, and
      maximizing QOL.

PMID- 18090189
TI  - Drifting in a shrinking future: living with advanced heart failure.
AB  - BACKGROUND: Patients with advanced heart failure (HF) have an uncertain prognosis
      and low rates of advance care planning and hospice use. The purpose of this study
      was to describe how patients view and plan for their future. METHODS: Twenty-four
      (N = 24) patients took part in a semistructured interview in which they were
      asked to describe their experiences in living with heart disease and their
      understanding and planning for their future. Interviews were transcribed and
      analyzed using the constant comparative method to generate a grounded theory.
      RESULTS: The core category, "Living with HF," encompassed the subcategories of
      "My Experience of HF," "Help with HF," and "My Future with HF." This article
      reports on "My Future with HF." Patients wanted to discuss how HF affected their
      future with their providers, but initiation of these discussions was difficult
      and the absence of discussion led to frustration. Patients did not find specific
      life expectancy estimates helpful in coping or planning their future care.
      CONCLUSIONS: Patients with advanced HF do not plan well for end-of-life care and
      tend to drift along while vaguely hoping for the best. End-of-life care in
      advanced HF should address difficulties in decision making and provider
      communication.

PMID- 18090190
TI  - Outpatient nursing clinic for congenital heart disease patients: Copenhagen
      Transition Program.
AB  - Adolescents with congenital heart disease need support transitioning from
      childhood to adulthood. To become independent, adolescents need to possess
      knowledge about the disease and how to handle life with congenital heart disease.
      Outpatient nursing clinics can address issues relevant for adolescents. Creating
      an environment in which worries and questions can be discussed better prepares
      adolescents to meet the struggles of living with congenital heart disease. The
      Copenhagen Transition Program was established in 2004. This outpatient nursing
      clinic was established by (1) defining the target group, (2) conducting a
      literature review, (3) collaborating with interdisciplinary colleagues, (4)
      scheduling visits to the transition-nursing clinic, (5) arranging clinic visits,
      (6) charting, and (7) testing and evaluating the clinic. Adolescents with
      congenital heart disease are invited to a consultation with a specially trained
      nurse, and it is the patients themselves who decide the content of the
      consultation. Topics such as knowledge about the disease, endocarditis, acute
      situations, nutrition, contraception, alcohol/drugs, smoking, physical activity,
      sleep/rest, and education may be discussed. Parents are asked not to participate.

PMID- 18090191
TI  - The effects of a symptom management intervention on symptom evaluation, physical
      functioning, and physical activity for women after coronary artery bypass
      surgery.
AB  - The purpose of this subset analysis was to examine the effect of a symptom
      management (SM) intervention on postoperative symptom evaluation, physical
      functioning, and physical activity among the female participants (N = 40) of the
      larger parent study of coronary artery bypass graft patients aged 65 years and
      older. The intervention group (n = 23) had significantly lower fatigue scores at
      6 weeks (Z = 1.96, P < .05) and higher levels of physical activity (Z = -1.71, P
      < .05) reflected in the expended kcal(-1) x kg x d(-1), as measured by the
      activity diary at 3 months after coronary artery bypass graft surgery. At 6 weeks
      and 3 months after surgery, there were significant correlations between cardiac
      surgery-related recovery symptoms (shortness of breath, fatigue, depression,
      incision pain, and sleep problems) and physical functioning (physical, vitality,
      and bodily pain functioning subscale scores), with correlations ranging from 0.31
      to 0.46. Given that this was a subset analysis of a larger study, significant
      differences were not expected for all variables. Study findings support the need
      for a targeted (women-focused) and tailored (self-management recovery)
      intervention to assist females in recovering from coronary artery bypass graft
      surgery to improve symptom management, thereby enhancing physical functioning and
      physical activity outcomes.

PMID- 18090192
TI  - Health-related quality of life in patients with coronary artery disease.
AB  - BACKGROUND AND RESEARCH OBJECTIVES: :In recent years, health-related quality of
      life (HRQoL) has been increasingly used as an indicator of health outcome. The
      aims of the study were to compare the HRQoL of patients with coronary artery
      disease (CAD) to patients without CAD and also to determine the HRQoL of patients
      with CAD and the factors affecting their quality of life. SUBJECTS AND METHODS:
      Patients with CAD who attend the outpatients' clinic in the Cardiology Department
      at Trakya University's Medicine Faculty Hospital agreed to be interviewed. One
      hundred patients with CAD and 100 people serving as patients without CAD were
      included in this cross-sectional study. Patients with CAD and patients without
      CAD were matched by age, sex, marital status, and income. Health-related quality
      of life was measured with the generic HRQoL instrument. RESULTS AND CONCLUSIONS:
      CAD patients' HRQoL scores differed significantly from patients without CAD.
      Compared to patients without CAD, the HRQoL of patients with CAD was lower in the
      dimensions of mobility (P < .001), hearing (P = .022), breathing (P < .001),
      elimination (P = .035), usual activities (P < .001), mental function (P = .004),
      discomfort and symptoms (P = .018), vitality (P = .006), sexual activity (P <
      .001), and total score (P < .001). Patients with CAD had lower HRQoL scores than
      patients without CAD. In patients with CAD, age and sex independently affected
      the HRQoL. Older patients and women had worse HRQoL. Coronary artery disease
      negatively affects HRQoL. It is thought that interventions to increase patients'
      quality of life may improve their HRQoL.

PMID- 18090193
TI  - Factors associated with caregiver depressive symptoms, outcomes, and perceived
      physical health after coronary artery bypass surgery.
AB  - BACKGROUND: Coronary artery bypass surgery patients often rely on spouses for
      assistance during recovery. Caregiving may be stressful, adversely affecting
      caregiver physical and emotional health and, therefore, ability to provide care.
      OBJECTIVE AND METHODS: This cross-sectional correlational study investigated
      factors associated with caregiver depressive symptoms, outcomes, and perceived
      physical health. Using a model from existing theories, these dependent variables
      were considered "health-related quality of life" outcomes. A convenience sample
      of 166 coronary artery bypass spouse caregivers completed surveys on patient
      health status, caregiver personality and relationship factors, task difficulty,
      depressive symptoms, caregiver outcomes, and perceived physical health. RESULTS:
      Using regression analysis, worse patient proxy health ratings and less personal
      mastery were associated with greater caregiver depressive symptoms. Being a
      female caregiver, worse patient proxy health ratings, lower mutuality, and more
      caregiver depressive symptoms were associated with negative caregiver outcomes.
      Younger spousal age and worse patient proxy health ratings were associated with
      worse caregiver perceived physical health. CONCLUSION: Although further
      longitudinal investigations are recommended, findings suggest that helping
      coronary artery bypass spouse caregivers master their role, improve their
      relationship with the patient, and avoid or reduce depressive symptoms can
      improve caregiver outcomes and are therefore areas for possible intervention.

PMID- 18090194
TI  - Self-reported adjustment to implanted cardiac devices.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Although implantations of devices to support
      cardiovascular function are increasing, little is known about the factors
      involved in adjusting psychologically to having an implanted device. This study
      provides factor analysis of the Implanted Device Adjustment Scale (IDAS) and self
      reported data on quality of life, mood states, and global adjustment. SUBJECTS
      AND METHODS: This cross-sectional correlational design study included 174
      subjects (46 women and 128 men). A convenience sample was recruited from
      electrophysiology practices in 2 large Midwestern cities. Subjects completed the
      IDAS, the SF-36 quality-of-life measure, the Profile of Mood States, and a device
      adjustment visual analog scale. RESULTS AND CONCLUSIONS: The factor analysis
      produced 4 subscales for the IDAS: fear/anxiety, attitude, preparation, and body
      awareness. Perceived adjustment was "good" for 89% of persons and was unrelated
      to age, sex, type of device, and whether a shock was received. All 4 subscales of
      the IDAS correlated negatively with adjustment (higher IDAS score means poorer
      adjustment). The overall IDAS was internally consistent with a Cronbach alpha =
      .89. Adjustment, as measured by the overall IDAS, had a weak but significant
      relationship with measures of quality of life including the mental component
      summary scale of the SF-36 (r = 0.19), but not the physical component summary
      scale of the SF-36. All the Profile of Mood States subscales correlated
      positively with the IDAS subscale anxiety/fear with the exception of
      vigor/activity which had a negative correlation. No sex differences in total
      adjustment were seen in this group of patients, although there were differences
      in body awareness, physical functioning, and fatigue. Although patients with
      implanted cardioverter defibrillator were more fearful/anxious than patients with
      pacemaker only, no differences in total adjustment were seen between the 2
      groups. A better understanding of the experience of adjusting to an implanted
      device is foundational to the development of appropriate interventions.

PMID- 18090195
TI  - Brief screen to identify 5 of the most common forms of psychosocial distress in
      cardiac patients: validation of the screening tool for psychological distress.
AB  - OBJECTIVE: To develop and validate a brief psychosocial screening tool (Screening
      Tool for Psychological Distress [STOP-D]) for use in the outpatient cardiology
      setting. BACKGROUND: Psychosocial factors contribute significantly to the
      morbidity and mortality associated with coronary artery disease. Yet, it is often
      considered overly burdensome to implement full-scale psychological assessments
      for every patient. METHODS: Over 3 months, 194 cardiac patients were
      consecutively recruited from 3 cardiac clinics: heart transplant (pre and post),
      cardiac rehabilitation, and adult congenital heart. Subjects filled out a
      questionnaire that included: (1) demographics, (2) STOP-D, (3) Beck Depression
      Inventory-II, (4) Beck Anxiety Inventory, (5) State-Trait Anger Expression
      Inventory-2, and (6) MOS Social Support Survey. RESULTS: Analyses reveal all STOP
      D items are highly correlated with the corresponding measures and have robust
      receiver operating characteristic curves. Severity scores on STOP-D-depression
      and STOP-D-anxiety correlate well with established severity cutoff scores on the
      Beck Depression Inventory and the Beck Anxiety Inventory, respectively.
      CONCLUSIONS: Overall, the STOP-D performs very well when compared with other
      longer and validated measures. The STOP-D is a 5-item self-report measure, which
      provides severity scores for: depression, anxiety, stress, anger, and poor social
      support. The STOP-D is self-administered and takes between 1 and 2 minutes to
      fill out, gives valid severity scores on 5 key areas of psychological distress
      (depression, anxiety, stress, anger, and poor social support), requires no
      scoring, and is free to use.

PMID- 18090197
TI  - Temperature, humidity, and ultraviolet B radiation predict community respiratory
      syncytial virus activity.
AB  - To obtain knowledge of how meteorological conditions affect community epidemics
      of respiratory syncytial virus (RSV) infection, RSV activity was recorded year
      round in 9 cities that differ markedly in geographic location and climate. Local
      weather conditions were correlated with weekly or monthly RSV cases. Similar
      reports from other areas varying in climate were also reviewed. Results
      demonstrated that for all sites combined, weekly RSV activity was related to
      temperature in a bimodal fashion, with peaks of activity at temperatures more
      than 24-30 degrees C and at 2-6 degrees C. RSV activity also was greatest at 45
      65% relative humidity. RSV activity was inversely related to ultraviolet B (UVB)
      radiance at 3 sites where this could be analyzed; the fourth site had minimal
      amounts of annual UVB radiance. At sites with persistently warm temperatures and
      high humidity, RSV activity was continuous throughout the year, peaking in summer
      and early autumn. In temperate climates, RSV activity was maximal during winter,
      correlating with lower temperatures. In areas where temperatures remained cold
      throughout the year, RSV activity again became nearly continuous. These data led
      us to conclude that community activity of RSV is substantial when both ambient
      temperatures and absolute humidity are very high, perhaps reflecting greater
      stability of RSV in aerosols; transmission of RSV in cooler climates is inversely
      related to temperature, possibly as a result of increased stability of the virus
      in secretions in the colder environment; and UVB radiation may inactivate the
      virus in the environment or influence susceptibility to RSV by altering host
      resistance.

PMID- 18090198
TI  - Diagnostic assays for respiratory syncytial virus disease.
AB  - Respiratory syncytial virus (RSV) infection in the United States and worldwide is
      a major cause of morbidity and mortality and of outpatient visits,
      hospitalizations, and increased healthcare costs. Effective diagnosis of viral
      respiratory infections, as well as recognition and understanding of the benefits
      and limitations of diagnostic laboratory testing, is essential. Serology is not
      useful for diagnosing acute respiratory illness. Antigen-based assays are widely
      available, easy to use, provide rapid results, and are inexpensive; however, they
      are less sensitive than cell culture utilizing good specimen collection and
      processing techniques. Cell culture, which was previously considered the gold
      standard for identification of respiratory viruses, in many settings is being
      replaced by nucleic acid amplification assays that have even greater sensitivity
      and provide more rapid results. Although available chiefly at large hospitals and
      reference laboratories, molecular assays may fulfill the need for more sensitive
      and rapid diagnosis of illnesses caused by respiratory viruses. The seasonality
      of RSV as measured by nucleic acid amplification-based assays appears to be
      broader with better identification of patient populations that harbor RSV between
      yearly epidemic peaks compared with the seasonality of RSV as measured by the
      older techniques. As these new diagnostic methodologies emerge, guidelines will
      be needed to direct their appropriate use in the diagnostic laboratory.

PMID- 18090199
TI  - Variation in timing of respiratory syncytial virus outbreaks: lessons from
      national surveillance.
AB  - Respiratory syncytial virus (RSV) is the leading cause of pneumonia and
      bronchiolitis in infants and children. Immune prophylaxis can reduce the risk of
      severe RSV disease among some high-risk infants. A summary and update of analyses
      using National Respiratory and Enteric Virus Surveillance System (NREVSS) data is
      provided to explore using surveillance data to better define the timing of RSV
      activity and RSV immune prophylaxis. The methodology used was that outlined in a
      study by Mullins et al (Pediatr Infect Dis J. 2003;22:857-862), which analyzed
      weekly antigen detection data reported by laboratories to NREVSS. Data reported
      to NREVSS between 1990 and 2006 were used to assess seasonality among regional,
      state, and local areas. Season onset, offset, and duration were calculated for
      each year and each laboratory, and compared with the U.S. Census region and
      national median measurements. Results demonstrated a distinct winter peak of RSV
      activity each year. The extent of variation in the timing of RSV activity in a
      community from year to year makes it difficult to predict the timing of RSV
      outbreaks. In addition, the onset timing can vary between communities, even those
      in close proximity, during the same year. There are, however, regional community
      patterns that may help guide timing of immune prophylaxis. For example, the South
      region exhibited an earlier median season onset and longer duration than the
      other regions, with median onset week 47 and duration 16 weeks. In contrast, the
      Midwest exhibited a significantly later median onset and shorter duration than
      the other regions, with median onset week 1 of the following year and duration 13
      weeks. Therefore, analyses of NREVSS data show that using surveillance data to
      tailor the timing of immune prophylaxis precisely will be difficult. Surveillance
      data can, however, be used to determine how well national patterns represent
      local patterns. Further analyses are needed to determine how local surveillance
      data can be used to guide timing of immune prophylaxis.

PMID- 18090200
TI  - Respiratory syncytial virus season and hospitalizations in the Alaskan Yukon
      Kuskokwim Delta.
AB  - From 1993 to 1996, Alaska Native infants younger than 1 year of age from the
      Yukon-Kuskokwim Delta region in Alaska experienced a respiratory syncytial virus
      (RSV) hospitalization rate 5 times higher than the U.S. general infant population
      rate. This article describes the trends in hospitalization and prolonged annual
      season of RSV hospitalizations in Yukon-Kuskokwim children from 1993 to 2004 and
      discusses factors associated with high rates of RSV hospitalization and the
      impact of interventions to decrease RSV hospitalizations in this population.

PMID- 18090201
TI  - Respiratory syncytial virus laboratory surveillance and hospitalization trends in
      South Texas.
AB  - Surveillance of seasonal variations in respiratory syncytial virus (RSV)
      outbreaks is an important component in clinical decision-making. A retrospective
      analysis of 11 years of laboratory-based RSV surveillance and 7 years of
      hospitalization data was carried out to better define the onset and duration of
      the RSV season in South Texas, as well as to evaluate the clinical impact and
      timing of RSV outbreaks on the number of infants hospitalized with RSV infection.
      All but one of the seasons examined lasted longer than the national and southern
      seasons reported by the Centers for Disease Control and Prevention. In addition,
      most seasons started earlier and ended later than the national and regional
      seasons. Considerable parallels were noted between RSV hospital admission
      frequency and number of RSV-positive tests, as determined by rapid antigen
      detection or viral culture. Taken together, these results reflect the clinical
      utility of RSV surveillance data and highlight the impact of RSV on infant
      hospitalization.

PMID- 18090202
TI  - Respiratory syncytial virus seasonality in southeast Florida: results from three
      area hospitals caring for children.
AB  - Southeast Florida generally experiences longer seasonal epidemics of respiratory
      syncytial virus (RSV) than other parts of the country. In this report, the
      primary objective was to more accurately define the onset, peak, and duration of
      the RSV season in Southeast Florida. The results obtained for this region were
      also compared with those reported for the state and for the nation. Seasonal
      patterns for RSV in Southeast Florida were analyzed based on the total number of
      RSV tests performed, number of positive tests, and percent of positive tests in
      children presenting with bronchiolitis to 3 emergency departments from January
      2003 through December 2006. RSV was detected by rapid diagnostic testing and
      considered to be present at epidemic levels when at least 10% of performed tests
      were positive during a given month. During the entire 12 months of 2003 and 2006,
      RSV was detected above epidemic levels. The RSV-detection test positivity rate
      was less than 10% in only 6 months of 48 total months of observation, but during
      the months that were below epidemic threshold, RSV was still frequently
      identified. RSV activity increased during July, peaked during October, and waned
      during the spring months. These findings were nearly identical to those recently
      reported in other studies, confirming that RSV circulated at epidemic levels in
      Southeast Florida during most of the 4-year observation period and remained a
      significant cause of respiratory disease and hospitalization throughout the year.
      Strategies for RSV prophylaxis in at-risk children in South Florida should
      consider results of local RSV test detection.

PMID- 18090204
TI  - Variance of angular insertion depths in free-fitting and perimodiolar cochlear
      implant electrodes.
AB  - OBJECTIVE: To assess the variance in cochlear implant electrode insertion depth
      in degrees around the modiolus (angular insertion depth) in free-fitting and
      perimodiolar electrode arrays. MATERIALS AND METHODS: Twenty-eight fresh human
      temporal bones were implanted with free-fitting cochlear implant electrodes, and
      18 bones were implanted using perimodiolar electrode arrays. Specimens were
      embedded, and 2-dimensional radiographs were obtained to assess angular insertion
      depths. Histologic serial sections of undecalcified bones were then evaluated to
      analyze intracochlear electrode positions. Finally, linear surgical insertion
      depths (in millimeters) were correlated with angular insertion depth (degrees
      around the modiolus). RESULTS: A moderate variance of angular insertion depth was
      documented for both free-fitting and perimodiolar electrode arrays. Full
      insertions into the scala tympani ranged from 540 to 630 degrees with free
      fitting arrays and from 270 to 375 degrees with perimodiolar electrodes. In free
      fitting devices, a linear relationship between linear (in millimeters) and
      angular (degrees) insertion depths was observed. Insertions into scala vestibuli
      were observed in 9 of 28 and 5 of 18 of the specimens for free-fitting and
      perimodiolar electrodes, respectively. Additionally, scala vestibuli insertions
      showed greater angular insertion depths when compared with scala tympani
      implantations. CONCLUSION: Variances in angular insertion depths seem to be
      moderate and similar in free-fitting and perimodiolar electrode arrays. Scala
      vestibuli insertions showed greater angular insertion depths than comparable
      insertions into the scala tympani. In perimodiolar electrodes, angular insertion
      depths equal or greater than 390 degrees suggested scala vestibuli placement.

PMID- 18090207
TI  - A century ago: Adam Politzer published the first volume of his History of
      Otology.
AB  - In 1907, Adam Politzer published his famous History of Otology, which is already
      considered the best reference in the history of otology. This article shortly
      describes its content, the compliments the text got from Politzer's colleagues,
      and how Politzer was able to write it.

PMID- 18090212
TI  - How do we best balance optimal timing of FDG PET-CT imaging?

PMID- 18090208
TI  - Common cavity deformity.

PMID- 18090213
TI  - 99mTc-MIBI brain SPECT as an indicator of the chemotherapy response of recurrent,
      primary brain tumors.
AB  - BACKGROUND: Malignant brain tumors carry a pejorative prognosis and necessitate
      aggressive therapy. Chemotherapy can be used in cases of tumor recurrence. With
      limited response rate and potential toxicity to chemotherapeutic treatment in
      patients with recurrent glioma, reliable response assessment is essential. AIM:
      To define the place of 99mTc hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI)
      Single Positron Emission Computed Tomography (SPECT) in monitoring chemotherapy
      response in recurrent primary brain tumors. METHODS: In a retrospective analysis,
      thirty patients were investigated with MIBI SPECT. Imaging was performed 1h after
      the intravenous injection of 555 MBq of 99mTc-MIBI using a dedicated SPECT
      system. A MIBI uptake index (UI) was computed as the ratio of counts in the
      lesion to those in contralateral region. For all patients, we compared changes
      over time in UI with MRI and clinical data. RESULTS: The changes in UI agreed
      well with the clinical and MRI-based assessments in 97% of cases. In 44% of these
      cases, the scintigraphic response appeared before the MRI response. In instances
      of treatment failure or rebound, the concordance between scintigraphy and MRI was
      52%, and the scintigraphic response appeared before the MRI response in 48% of
      cases. CONCLUSION: This study confirms our previous results obtained on a short
      series of patients with recurrent glioma, concerning the usefulness of MIBI SPECT
      in prediction of chemotherapy response. Moreover, in cases of tumor progression,
      we show that MIBI SPECT is an earlier indicator of escape from chemotherapy, an
      average 4 months before MRI changes.

PMID- 18090214
TI  - Study of 99mTc-annexin V uptake in apoptotic cell models of Parkinson's disease.
AB  - OBJECTIVE: To investigate the feasibility of radiolabelled annexin V imaging for
      early diagnosis of Parkinson's disease. METHODS: 99mTc-HYNIC-annexin V was
      prepared and its binding to apoptotic cell models of Parkinson's disease was
      studied in vitro. Cellular models of Parkinson's disease were produced by
      administering different concentrations of 1-methyl-4-phenylpyridinium to PC12 and
      SH-SY5Y cell lines. Cell apoptosis rates were analysed by flow cytometry. Annexin
      V was labelled with 99mTc by hydrazinonicotinamide (HYNIC). Cell binding studies
      were carried out using cellular models of Parkinson's disease. Cell uptake
      studies were also performed after different levels of MPP treatment, and the
      correlation between the degree of apoptosis and Tc-HYNIC-annexin V uptake was
      analysed. RESULTS: The specific activity of 99mTc-HYNIC-annexin V was 3.7-74 x 10
      Bq.mg protein. In-vitro binding of 99mTc-HYNIC-annexin V to model cells was
      specific, saturable and time dependent. Scatchard analysis gave a Kd of 7.16+/
      1.78 nmol.l, Bmax values of 179+/-33 fmol per 10(6) cells (PC12) and 220+/-26
      fmol per 10(6) cells (SHSY5Y). MPP at different concentrations can induce cell
      apoptosis in a dose-dependent manner; cellular uptake of 99mTc-HYNIC-annexin V as
      indicated by membrane-bound radiolabelled annexin V activity was linearly
      correlated with total fluorescence, as observed by FITC-annexin V flow cytometry
      (PC12: r=0.924; SH-SY5Y: r=0.937, P<0.01). CONCLUSIONS: 99mTc-HYNIC-annexin V
      retains its receptor-binding activity and has a high affinity to cellular models
      of Parkinson's disease. The uptake of radioactivity correlated well with cell
      apoptosis rates; thus, 99mTc-annexin V is a potential imaging agent with which to
      detect early neuron damage in Parkinson's disease.

PMID- 18090215
TI  - Assessing response to chemotherapy in metastatic melanoma with FDG PET: Early
      experience.
AB  - OBJECTIVE: The management of metastatic melanoma remains challenging with only
      modest response rates to chemotherapy but the need to identify the best re
      staging techniques remains paramount. This study evaluates our early experience
      in the use of FDG PET-CT in the assessment of early response to chemotherapy in
      metastatic melanoma. METHODS: FDG PET-CT was performed at baseline and following
      two or three cycles of combination or single agent chemotherapy in seven
      patients. Response was assessed visually as complete, partial metabolic response
      or progressive disease. RESULTS: There was intense FDG uptake in all metastases
      at baseline. Following two to three cycles of chemotherapy, there was a complete
      metabolic response (CMR) in one patient, partial metabolic response (PMR) in two
      patients and progressive metabolic disease (PMD) in the remaining three patients.
      Survival was 679 days in the single patient with a CMR, median of 206 and 129
      days in the patients with PMR and PMD respectively. CONCLUSION: This pilot study
      demonstrates the potential use of FDG PET as a biomarker in early response
      assessment to chemotherapy in metastatic melanoma. PET-CT already plays in
      integral role in staging high risk melanoma patients and it may also have a
      promising role in assessing response to current and novel therapies. Further
      larger studies examining specific therapies and optimal timing are required.

PMID- 18090216
TI  - Is thyroglobulin the stronger indicator for progressive disease than the other
      conventional factors in same age patient groups with differentiated thyroid
      cancer?
AB  - AIM: To determine the thyroglobulin cut-off value as an indicator for progressive
      disease and to research relationships between sex, histological type, extra
      capsular invasion and progressive disease in differentiated thyroid cancer.
      METHODS: Four hundred and eight patients were evaluated retrospectively. One
      hundred and fifty-eight patients (group 1) treated for progressive disease and
      166 patients (group 2) that were ablated for thyroid remnant were included in our
      study. Sex, age, histological type, presence of extra-capsular invasion at the
      diagnosis and L-thyroxine off thyroglobulin values (6-12 months after the
      ablation) were obtained. Data were analysed by statistical methods. RESULTS:
      There was no statistically significant difference for ages (group 1, 45.3+/-16.1
      years; group 2, 47+/-12 years, P>0.05). The chi-squared test revealed
      statistically significant differences for histological type (P>0.05) and extra
      capsular invasion (P<0.001) but not for sex (P>0.05). Feasible cut-off level,
      sensitivity and specificity were found as a 10 ng.ml thyroglobulin value, 79% and
      97%, respectively. However, sensitivity and specificity were 80%, 92% for 5 ng.ml
      and 82% for 2 ng.ml thyroglobulin levels. Multivariate analysis showed that a 10
      ng.ml thyroglobulin cut-off value and extra-capsular invasion were independent
      prognostic factors. CONCLUSION: Increased thyroglobulin level, extra-capsular
      invasion and follicular type were poor prognostic factors but sex was not,
      whereas only extra-capsular invasion and increased thyroglobulin level were
      independent prognostic indicators for our groups. A 10 ng.ml thyroglobulin level
      was a feasible cut-off and seemed to be a stronger factor than other indicators
      to predict progressive disease.

PMID- 18090217
TI  - Comparison of early and delayed FDG PET for evaluation of biliary stricture.
AB  - OBJECTIVE: We assessed whether delayed FDG PET imaging is more useful for the
      evaluation of biliary stricture in differential diagnosis of malignancy from
      benign disease. METHODS: Thirty-seven patients who underwent FDG PET for
      differential diagnosis of the disease causing biliary stricture were included.
      FDG PET imaging was performed at 70+/-12 min (early) post FDG injection and
      repeated 188+/-27 min (delayed) after injection only in the abdominal region.
      Image analysis was performed with visual interpretation and using a semi
      quantitative method if lesion was visible on the PET image. The semi-quantitative
      analysis using the standardized uptake value (SUV) was determined for both early
      and delayed images (SUVearly and SUVdelayed, respectively). The tumour-to-normal
      liver (T/L) ratio was also calculated. RESULTS: The final diagnosis was
      cholangiocarcinoma in 29 and benign disease in eight patients. In cases of
      cholangiocarcinoma, visual analysis of FDG PET using the delayed images, improve
      the diagnosis with one more patient correctly identified. For early and delayed
      FDG PET, sensitivities were 82.8% and 86.2%, respectively; specificities were
      87.5% for both; and accuracies were 83.8% and 86.5%, respectively. Both SUV and
      T/L ratio derived from delayed images were significantly higher than those
      derived from early images for cholangiocarcinoma (P<0.0002 and P<0.0001,
      respectively). CONCLUSION: FDG PET could be useful for differential diagnosis of
      malignancy from benign disease in patients with biliary stricture. Especially,
      the delayed targeted FDG PET imaging can be recommended in those patients when
      early imaging is negative or equivalent, because of increased lesion uptake and
      increased lesion to background contrast ratio.

PMID- 18090218
TI  - Segmental and total oesophageal transit time in patients with corrosive-induced
      oesophageal stricture.
AB  - INTRODUCTION: The mainstay of treatment of corrosive oesophageal strictures is
      endoscopic dilatation. However, even after adequate dilatation, some patients may
      continue to have dysphagia. An associated oesophageal motor dysfunction in such
      patients may contribute to the persistence of dysphagia. AIM: To assess
      oesophageal motor dysfunction in patients with corrosive strictures using
      segmental and total oesophageal transit time by radionuclide scintigraphy.
      METHODS: Thirty-five patients with corrosive-induced oesophageal strictures were
      evaluated after having achieved a dilatation of 15 mm. All patients underwent
      barium swallow and upper endoscopy for assessment of stricture(s). Oesophageal
      motility was assessed by radionuclide scintigraphy using Tc sulfur colloid. Total
      oesophageal transit time (ETT) and segmental (upper, middle and lower third of
      oesophagus) ETT were determined. RESULTS: Thirty-five patients (age 18-53 years)
      were evaluated. Twenty-eight (80%) patients had a single stricture while seven
      (20%) had either two or three strictures. Eighteen patients had no dysphagia, 13
      patients had grade 1 dysphagia and four patients grade 2 dysphagia. Total ETT was
      prolonged in 12 patients. Upper, middle and lower third ETT was prolonged in
      four, seven and six patients, respectively. Length of the stricture correlated
      with prolongation of ETT as 6.66% patients with length < or = 5 cm, and 53.84% of
      patients with length >5 cm had prolonged total ETT (P=0.019). Patients with
      tortuous stricture had more prolongation of ETT as compared to those with
      straight strictures though it did not reach statistical significance. No
      significant correlation was observed between number of strictures and
      prolongation of total ETT. The severity of dysphagia correlated with prolongation
      of total ETT (P=0.011). CONCLUSION: Oesophageal transit time as assessed by
      scintigraphy is prolonged in one-third of patients with corrosive-induced
      oesophageal strictures despite having achieved adequate dilatation. Prolongation
      of ETT correlates with length of the stricture and severity of dysphagia
      correlates with prolongation of total ETT. These observations suggest impairment
      of oesophageal motility in these patients.

PMID- 18090219
TI  - Female breast surface radiation exposure during FDG PET/CT examinations.
AB  - BACKGROUND: The combined positron emission tomography (PET) and computed
      tomography (CT) scanners have been developed in which CT data can be used for
      both anatomical landmarks and attenuation correction of PET images. However, this
      modality potentially introduces more radiation burden to patients compared to
      conventional PET scanning as a result of the added radiation exposure received
      from CT examination. The purpose of our study was to determine the breast
      radiation doses of combined PET/CT examination. MATERIAL AND METHODS: Patients'
      superficial breast doses were calculated using thermoluminescence dosimeters
      (TLDs) placed onto the surface of the breasts. TLDs were positioned before FDG
      injection and removed after 24 h. We also determined the average superficial and
      glandular breast radiation doses from the anthropomorphic dosimetric phantom
      imaged using similar CT protocol (low dose) to the patients' study. RESULTS: The
      mean superficial breast dose of the breast skin measured from the PET/CT studies
      was 14.42+/-2.41 mGy. The average superficial and glandular breast doses of the
      anthropomorphic phantom measured from the low-dose CT was 9.50 mGy and 5.94 mGy,
      respectively. CONCLUSION: This study showed that radiation exposure to the
      breasts during PET/CT was higher than the recommended doses. Therefore, combined
      PET/CT scanning must be used for essential indications, particularly in women of
      reproductive age and preferentially a low-dose CT protocol should be implemented
      to avoid overexposure in such patients.

PMID- 18090220
TI  - Evaluation of reconstruction techniques for lung single photon emission
      tomography: a Monte Carlo study.
AB  - BACKGROUND: In studies of the distribution of lung function, the image quality of
      lung single photon emission computed tomography (SPECT) is important and one
      factor influencing it is the reconstruction algorithm. AIM: To systematically
      evaluate ordered subsets expectation maximization (OSEM) and compare it with
      filtered back-projection (FBP) for lung SPECT with Tc. METHODS: The evaluation of
      the number of iterations used in OSEM was based on the image quality parameter
      contrast. The comparison between OSEM and FBP was based on trade-off plots
      between statistical noise and spatial resolution for different filter parameters,
      collimators and count-levels. A Monte Carlo technique was used to simulate SPECT
      studies of a digital thorax phantom containing two sets of activity: one with a
      homogeneous activity distribution within the lungs and the other with superposed
      high- and low-activity objects. Statistical noise in the reconstructed images was
      calculated as the coefficient of variation (CV) and spatial resolution as full
      width at half-maximum (FWHM). RESULTS: For the configuration studied, the OSEM
      reconstruction in combination with post-filtering should be used in lung SPECT
      studies with at least 60 MLEM equivalent iterations. Compared to FBP the spatial
      resolution was improved by about 1 mm. For a constant level of CV, a four-fold
      increase in count level resulted in an increased resolution of about 2 mm.
      Spatial resolution and cut-off frequency depends on what value of noise in the
      image is acceptable also increased by using a low-energy, high-resolution
      collimator for CV values above 3%. The choice of noise-reducing filter and cut
      off frequency depends on what value of noise in the image is acceptable.

PMID- 18090221
TI  - Body-contour versus circular orbit acquisition in cardiac SPECT: assessment of
      defect detectability with channelized Hotelling observer.
AB  - BACKGROUND: The resolution of a gamma camera is depth-dependent and worsens with
      increasing distance to the camera resulting in a loss of fine details in SPECT
      images. A common approach to reduce the effects of this resolution loss is to
      utilize body-contour acquisition orbits. Even though body-contour orbits can
      improve resolution of reconstructed images their effect on lesion detection is
      not well known. OBJECTIVE: To investigate whether body-contour orbits offer
      better defect detection performance than circular orbits in cardiac SPECT.
      METHODS: The mathematical cardiac torso (MCAT) phantom was used to model Tc
      sestamibi uptake. A total of four phantoms (two male and two female) with eight
      defects (four locations and two sizes) were generated and projection data were
      simulated using an analytical projector with attenuation, scatter, collimator
      response and acquisition orbit modelling. The circular and body-contour
      projections were reconstructed using the OSEM algorithm with/without collimator
      response compensation. Defect detection performance was assessed by calculating
      area under the receiver operating characteristic (ROC) curve for channelized
      Hotelling observer. RESULTS: The defect detection performance of circular and
      body-contour acquisition was very similar and the difference in the area under
      the ROC curve between the orbits was not statistically significant with or
      without collimator response compensation. The collimator response compensation,
      on the other hand, was noticed to be valuable and it provided significantly
      better defect detection performance than reconstruction without it regardless of
      the acquisition orbit type. CONCLUSIONS: We conclude that by replacing circular
      orbit with more complex body-contour orbit will not lead to statistically
      significant increase in defect detection performance in cardiac SPECT.

PMID- 18090222
TI  - Evaluation of different beta-counting systems involved in 90Y-Zevalin quality
      control.
AB  - BACKGROUND: 90Y-ibritumomab tiuxetan (90Y-Zevalin) is currently approved for
      radioimmunotherapy of patients with relapsed or refractory low-grade, follicular,
      or transformed B-cell non-Hodgkin's lymphoma. The radioimmunoconjugate may be
      administered to the patient only if the radiolabelling yield is higher than 95%.
      AIM: To evaluate different methods of quality control testing for an accurate and
      rapid determination of radiolabelling yield in the clinical routine. METHODS:
      Five beta-counting systems, involved in determining the yield of radiolabelled
      90Y-Zevalin, were compared: an autoradiography system (AS), a thin-layer
      chromatography (TLC) scanner system, a dose calibrator (DC), a liquid
      scintillation analyser (LSA) and high-performance liquid chromatography (HPLC).
      These instruments were also analysed in terms of efficiency, spatial resolution,
      analysis time, operating procedure level, cost and availability. RESULTS:
      Radiolabelling yields were comparable among all instruments except for DC whose
      values were dubious. Efficiency was 1.5+/-0.11 MDLU.s for the AS (where DLU means
      digital light unit), 3.5+/-0.2 kcps for the TLC analyser, 0.74+/-0.02 MBq for the
      DC, 15+/-0.12 kcps for LSA and 180+/-0.07 kcps for HPLC. Spatial resolution was 1
      mm for AS and 5 mm for the TLC analyser. The quality control test needed 8 min
      with AS and DC, 15 min with TLC and LSA, and 50 min with HPLC. CONCLUSIONS: The
      short analysis time, high sensitivity, simultaneous detection of multiple
      radioactive strips and low cost offered by AS make it a suitable tool for
      radioactivity analysis and quantification in a radiopharmacy laboratory.

PMID- 18090223
TI  - Adsorption of radiopharmaceuticals to syringes: setting up a reliable protocol
      for its assessment.
AB  - BACKGROUND: It is well known that various drugs, including radiopharmaceuticals,
      may adsorb to plastic syringes to different extents. Some reports suggest that
      adsorption can reach levels of almost 50%. The consequence of adsorption of a
      radiopharmaceutical and subsequent inadequate dosing can include an inappropriate
      diagnostic response in patients, an increase in the duration of investigation or
      treatment, and an increase in cost. AIM: To investigate the extent of adsorption
      of Tc-succimer to plastic syringes and to set up a reliable protocol for
      assessment of the extent of retention of drugs to single-use plastic syringes
      before a new syringe brand and/or radiopharmaceutical are introduced in a nuclear
      medicine department. METHODS: Radiopharmaceutical kits from two different
      manufacturers were compared for retention using syringes from three different
      producers. To assess the influence of dilution on retention, Tc-succimer
      preparations were further diluted with sodium chloride solution for injection.
      Syringes were filled to one-third of their capacity and incubated at room
      temperature before being emptied into vacuum vials. The radioactivity of the
      syringes was measured before and after emptying. The extent of retained
      radioactivity was calculated as a percentage of radioactivity in the syringe
      before emptying. RESULTS: Results show that adsorption of Tc-succimer
      considerably differs between syringe brands. The adsorption of undiluted Tc
      succimer in 30 min may exceed 50%. CONCLUSION: The findings show that measurement
      of retention in syringes and injection sets should be regarded as an essential
      aspect of quality assurance before radiopharmaceuticals, syringes and injection
      sets are used routinely.

PMID- 18090225
TI  - Flavonoids protect against cytokine-induced pancreatic beta-cell damage through
      suppression of nuclear factor kappaB activation.
AB  - OBJECTIVES: In the past few decades, the use of natural compounds, such as
      flavonoids, as anti-inflammatory agents has gained much attention. Our current
      study focuses on the preventive effects of quercetin, apigenin, and luteolin on
      cytokine-induced beta-cell damage. METHODS: Pancreatic beta-cells or islets were
      treated with cytokine mixtures in the presence or absence of flavonoids and the
      inhibitory effect of flavonoids against cytokine toxicity was determined.
      RESULTS: Treatment of RINm5F (RIN) rat insulinoma cells with interleukin 1beta
      (IL-1beta) and interferon gamma (IFN-gamma) induced cell damage. Quercetin,
      apigenin, and luteolin completely protected against IL-1beta- and IFN-gamma
      mediated cytotoxicity in RIN cells. Incubation with quercetin, apigenin, and
      luteolin resulted in a significant reduction in IL-1beta- and IFN-gamma-induced
      nitric oxide production, a finding that correlated well with reduced levels of
      the inducible form of NO synthase messenger RNA and protein. The molecular
      mechanism by which quercetin, apigenin, and luteolin inhibited inducible NO
      synthase gene expression appeared to involve the inhibition of nuclear factor
      kappaB (NF-kappaB) activation. The IL-1beta- and IFN-gamma-stimulated RIN cells
      showed increases in NF-kappaB binding activity, p50 and p65 subunit levels in
      nucleus, and IkappaB alpha degradation in cytosol compared with unstimulated
      cells. Quercetin, apigenin, and luteolin also prevented IL-1beta- and IFN-gamma
      mediated inhibition of insulin secretion. CONCLUSION: Quercetin, apigenin, and
      luteolin inhibited cytotoxicity in RIN cells and attenuated the decrease of
      glucose-stimulated insulin secretion in islets by IL-1beta and IFN-gamma.

PMID- 18090226
TI  - Reduction of oxidative stress by a new low-molecular-weight antioxidant improves
      metabolic alterations in a nonobese mouse diabetes model.
AB  - OBJECTIVES: We have previously established a nonobese diabetes mouse model
      characterized by moderate hyperglycemic levels, like those usually occurring in
      human type 2 diabetes. As oxidative stress is considered a major mechanism of
      progressive beta-cell damage in diabetes, we tested in this model the protective
      effects of a new low-molecular-weight antioxidant, namely, bis(1-hydroxy-2,2,6,6
      tetramethyl-4-piperidinyl)decandioate dihydrochloride (IAC). METHODS: Diabetes
      was induced in C57Bl/6J mice by streptozotocin (STZ) and nicotinamide (NA)
      administration. Two weeks later, STZ-NA mice were treated for 5 weeks with
      different doses of IAC (15 or 30 mg/kg per day intraperitoneally) and monitored
      for glycemia, insulinemia, glucose tolerance, and pancreatic insulin content.
      RESULTS: Streptozotocin-NA mice showed moderate hyperglycemia, hypoinsulinemia,
      glucose intolerance, growth impairment, and markedly reduced pancreatic insulin
      content (22% of controls). IAC-treated STZ-NA mice showed clear-cut reduction of
      hyperglycemia and attenuation of glucose intolerance, associated to higher
      residual pancreatic insulin content with respect to untreated diabetic animals.
      Plasma nitrotyrosine levels (an index of oxidative stress), enhanced 3-fold in
      diabetic mice, were significantly reduced by IAC treatment. Significant
      correlations were found between plasma nitrotyrosine values and either blood
      glucose levels or pancreatic insulin content. CONCLUSIONS: In the STZ-NA diabetic
      mouse model, the new antioxidant, IAC, improves diabetic metabolic alterations,
      likely by counteracting beta-cell dysfunction and loss associated with oxidative
      stress.

PMID- 18090227
TI  - Lymphatic vessel endothelial hyaluronan receptor 1 immunocytochemical staining
      for pancreatic islets and pancreatic endocrine tumors.
AB  - OBJECTIVES: Immunocytochemical staining for lymphatic vessel endothelial
      hyaluronan receptor 1 (LYVE-1) is able to recognize lymphatic vessel endothelium
      and pancreatic endocrine cells (PETs). Pancreatic endocrine tumors were studied
      for LYVE-1 immunocytochemical staining compared with normal pancreatic islets to
      detect possible presence of LYVE-1 in PETs. METHODS: Twenty-five cases of primary
      and metastatic PETs were immunocytochemically stained for LYVE-1, including
      insulinomas, glucagonomas, somatostatinoma, pancreatic polypeptidomas,
      gastrinomas, and nonfunctioning tumors. With routinely formalin-fixed and
      paraffin-embedded tissues, LYVE-1 immunostaining was performed with polyclonal
      goat antihuman LYVE-1. RESULTS: All normal pancreatic islet cells were positive
      for LYVE-1, whereas 2 cases of 25 PETs, 1 each of gastrinoma and nonfunctioning
      tumor, were positive for LYVE-1, retaining immunocytochemical reactivity of islet
      cells. CONCLUSIONS: Normal pancreatic islets were positive for LYVE-1, whereas
      only 2 of 25 PETs were positive, suggesting that most PETs lost LYVE-1 or
      contained below detectable levels of LYVE-1. The presence of LYVE-1 in pancreatic
      islets and in some PETs may suggest structure-function relationship of LYVE
      1/lymphatic vessel in hormone synthesis and secretion.

PMID- 18090228
TI  - Preferential increase of extracellular matrix expression relative to transforming
      growth factor beta1 in the pancreas during the early stage of acute hemorrhagic
      pancreatitis in rats.
AB  - OBJECTIVES: To elucidate the role of transforming growth factor (TGF) beta1 and
      extracellular matrix (ECM) after acute necrotizing pancreatitis, we studied the
      regulation of TGF-beta1 and ECM after induction of pancreatitis. METHODS: We
      examined the serial changes of levels of plasma TGF-beta1 by enzyme-linked
      immunoassay and expression of TGF-beta1 and ECM by Northern and Western blot
      analyses, respectively, in the pancreas after induction of sodium taurocholate
      induced acute pancreatitis. RESULTS: Plasma total (active and inactive) TGF-beta1
      levels at 3 hours after induction of pancreatitis were significantly increased
      compared with baseline values. The levels of TGF-beta1 messenger RNA (mRNA) were
      unaltered by day 2. Levels of fibronectin mRNA at 3 hours after induction of
      pancreatitis were already higher than the baseline values. Latency-associated
      peptide-TGF-beta1 showed a peak on day 7. Thus, the expression of ECM mRNA
      increased earlier than that of TGF-beta1 mRNA. CONCLUSIONS: These results suggest
      that the increase in plasma TGF-beta1 concentration probably results from the
      elevated secretion of TGF-beta1 from several cells and/or the redistribution of
      TGF-beta1 protein and that the increase in expression of ECM probably is
      associated with the activation of TGF-beta1. It is conceivable that both
      increased plasma concentration and focal activation of TGF-beta1 play an
      important role in ECM production during the early stage of acute pancreatitis.

PMID- 18090229
TI  - Acinar cell membrane disruption is an early event in experimental acute
      pancreatitis in rats.
AB  - OBJECTIVE: To test the hypothesis that disruption of acinar cell membranes is the
      earliest event that takes place after the onset of acute pancreatitis. METHODS:
      Cerulein and taurocholate pancreatitis were induced in rats. Furthermore,
      stimulation with different doses of bombesin, pilocarpine, and cerulein was
      performed. Five to 180 minutes after initiation of treatment, animals were
      killed. Disruption of cell membranes was detected by the penetration of the
      experimental animal's own albumin or immunoglobulin G (IgG) into acinar cells by
      immunocytological localization. Tissue was further analyzed by electron
      microscopy and electron microscopic immunostaining. RESULTS: Animals with
      pancreatitis displayed significantly greater antialbumin and anti-IgG
      immunostaining in the cytoplasm of acinar cells and in vacuoles in comparison
      with controls, confirming membrane disruption. This was not detectable after
      stimulation with bombesin, pilocarpine, and nonsupramaximal doses of cerulein.
      The first changes were seen after 5 minutes of induction of pancreatitis. Results
      were verified by electron microscopy and electron microscopic
      immunohistochemistry. CONCLUSIONS: The penetration of albumin and IgG into acinar
      cells indicates that wounding of their plasma membrane occurs at the onset of
      acute pancreatitis. Disruption of the membranes could be expected to allow the
      influx of calcium ions, causing massive intracellular alterations, and exit of
      molecules, such as enzymes from acinar cells.

PMID- 18090230
TI  - Evaluation of the effects of noniodinized and iodinized ionic contrast media and
      gadoteric acid in acute necrotizing pancreatitis: experimental study in rabbits.
AB  - OBJECTIVE: To evaluate the effects of iodine contrast media and gadoteric acid in
      acute necrotizing pancreatitis. METHODS: Fifty rabbits were distributed in 5
      groups: 10 rabbits were assigned in the control group (group 5) and 40 rabbits
      were assigned in the pancreatitis group, wherein acute necrotizing pancreatitis
      was induced through retrograde injection of 5% sodium taurocholate (1 mL/kg
      weight) in the main pancreatic duct. After 3 hours, they were randomized to
      receive endovenous iodinized nonionic contrast medium (group 1), iodinized ionic
      contrast medium (group 2), gadoteric acid (group 3), and physiological serum at
      0.9% (group 4). Six hours after induction of pancreatitis, these animals were
      reoperated. During surgery, pancreatic tissue flow through laser Doppler,
      hematometric values, biochemistry, and histopathology analysis by hematoxylin and
      eosin were done. Statistical analysis using Kruskal-Wallis, Fisher-Freeman
      Halton, and parametric t tests was performed. RESULTS: There was statistical
      significance when comparing tissue flow before and after induction of
      pancreatitis (P < 0.0001). Ionic and nonionic contrast media and gadoteric acid
      did not increase the grade of pancreatic necrosis (P > 0.05). CONCLUSIONS: Ionic
      and nonionic contrast media and gadoteric acid did not produce adverse effects in
      the present model of acute necrotizing pancreatitis.

PMID- 18090231
TI  - Remote preconditioning reduces microcirculatory disorders in pancreatic
      ischemia/reperfusion injury.
AB  - OBJECTIVES: Remote preconditioning (RPC) can protect from ischemia/reperfusion
      injury (IRI). We investigated the influence of RPC in pancreatic IRI. METHODS:
      Wistar rats were randomized to 2 hours of ischemia and 2 hours of reperfusion of
      a pancreatic tail segment with or without 15 minutes of infrarenal ischemia 60
      minutes before IRI. Microcirculatory measurements before ischemia and 1 and 2
      hours after reperfusion included functional capillary density and leukocyte
      adherence in postcapillary venules, quantified by intravital fluorescence
      microscopy. Histology and tissue myeloperoxidase activity were further parameters
      of pancreatic injury. RESULTS: Remote preconditioning caused an improvement of
      microcirculation (functional capillary density: 1 hour after reperfusion, 460 +/-
      13 vs 350 +/- 9 cm/cm2; 2 hours after reperfusion, 437 +/- 13 vs 295 +/- 13
      cm/cm2; P < 0.01) and reduced inflammatory tissue response (leukocyte adherence
      in postcapillary venules: 2 hours after reperfusion, 155 +/- 55 vs 748 +/- 187
      cells/mm2; P < 0.01). Histology was significantly better in preconditioned
      animals (IR, 8.1+/- 1.3 score points; RPC, 6.2 +/- 1.3 score points; P < 0.05).
      The difference in myeloperoxidase activity was not significant
      (ischemia/reperfusion [IR], 105 +/- 72; RPC, 245 +/- 209 mU x min(-1) x mg(ti)(
      1); P = 0.13). CONCLUSIONS: With our dynamic functional microcirculatory
      measurements, we could demonstrate that RPC is a feasible method to reduce
      experimental pancreatic IRI. This was seen in an attenuation of nutritive tissue
      perfusion and a reduction of inflammatory tissue response and a lower
      histological damage. Because it is easy to perform before organ harvest, RPC
      could be a step to improve organ procurement in pancreas transplantation.
      Clinical studies are the next step to evaluate RPC in pancreas transplantation.

PMID- 18090232
TI  - Clinical significance of swollen duodenal papilla in autoimmune pancreatitis.
AB  - OBJECTIVES: To evaluate the clinical significance of a swollen main duodenal
      papilla and the associated immunohistopathologic findings in patients with
      autoimmune pancreatitis (AIP). METHODS: Seventeen consecutive patients with AIP
      registered between April 2001 and October 2005 who underwent both endoscopic
      retrograde cholangiopancreatography and endoscopic biopsy were enrolled in this
      study. The endoscopic features, stromal inflammatory cell infiltrate (SICI), and
      results of immunohistochemical examination of the duodenal papilla using IgG4,
      CD3, and CD79a antibodies were retrospectively reviewed. These findings in the
      AIP patients were compared with those in 12 patients with chronic alcoholic tumor
      forming pancreatitis (CAP). The numbers of cells in the SICI and of IgG4-positive
      plasma cells per high-power field were counted in all the histopathologic
      specimens. RESULTS: A swollen main duodenal papilla was observed in 11 (11
      [64.7%]/17) patients with AIP and 4 (4 [33.3%]/12) patients with CAP (P < 0.05).
      Resolution of the swollen main duodenal papilla was observed in all of these 11
      patients with AIP (11 [100%]/11) in response to treatment with corticosteroids.
      On the other hand, the 6 patients without elevated serum IgG4 or a swollen
      duodenal papilla, but with a swollen pancreas, improved even without
      corticosteroid treatment. The number of cells in the SICI in the AIP patients was
      significantly higher than that in the CAP patients. Although in 13 of 17 AIP
      patients, infiltration by IgG4-positive plasma cells was detected in the duodenal
      papilla, no such significant infiltration of the duodenal papilla by IgG4
      positive plasma cells was observed in the patients with CAP (P < 0.05). More
      predominant T-cell infiltration of the duodenal papilla was recognized in the AIP
      patients than in the CAP patients (P < 0.05). CONCLUSIONS: These results suggest
      that a swollen main duodenal papilla with IgG4-positive plasma cell and T-cell
      dominant infiltration and an abundant stromal cell infiltrate are characteristic
      findings in AIP. We suggest that these findings may be valuable adjuncts to the
      diagnosis of AIP as well as for selecting suitable candidates for corticosteroid
      therapy.

PMID- 18090233
TI  - The integrin-extracellular matrix axis in pancreatic cancer.
AB  - Pancreatic cancer is the fifth leading cause of adult cancer death in the United
      States, with 5-year survival rates of only 1% to 4%. Current therapeutic
      strategies generally result in only a few months of extended life. Recent
      evidence from several independent laboratories in vitro and in vivo indicate that
      integrin-mediated cell attachment to the extracellular matrix (ECM), components
      of which are highly up-regulated in pancreatic cancer, evokes phenotypes and
      signaling pathways that regulate tumor cell growth and migration. In this review,
      we will discuss our current understanding of the role of the ECM in directing
      pancreatic cancer growth, progression, and metastasis. Topics covered include a
      survey of the existing literature regarding the in vivo and in vitro expression
      of the ECM and its cell surface receptors, the integrins, in pancreatic cancer;
      mechanisms involved in the integrin-ECM-mediated malignant phenotype; and future
      directions for the study of the integrin-ECM axis and its role in pancreatic
      cancer progression, including potential therapeutic strategies.

PMID- 18090234
TI  - Direct medical costs of acute pancreatitis hospitalizations in the United States.
AB  - OBJECTIVES: To determine the direct medical costs of hospitalizations for acute
      pancreatitis in the United States and analyze the demographic characteristics of
      hospitalized patients. METHODS: We searched the 2003 Healthcare Cost and
      Utilization Project-National Inpatient Sample for hospitalizations with a primary
      discharge diagnosis of acute pancreatitis. These were analyzed with respect to
      patient demographics, hospitalization rates, and total hospital charges and
      costs. RESULTS: The estimated total cost for acute pancreatitis admissions was
      $2.2 billion (95% confidence interval [CI], 2.0 billion-2.3 billion) at a mean
      cost per hospitalization of $9870 (95% CI, 9300-10,400), and a mean cost per
      hospital day of $1670 (95% CI, 1620-1720). Costs per hospitalization were higher
      in urban hospitals, teaching hospitals, and for patients older than 65 years,
      based on a longer length of stay (LOS). The hospitalization rate was 0.52 per
      1000 US population (95% CI, 0.48-0.56) for whites versus 0.76 per 1000 (95% CI,
      0.65-0.87) for blacks. CONCLUSIONS: Acute pancreatitis hospitalizations cost more
      than $2 billion annually, and certain population groups (blacks and older
      patients) have disproportionately high hospitalization rates. This study
      highlights the need for prevention efforts, particularly targeting high-risk
      groups, and for further studies to identify cost effective treatment strategies
      for acute pancreatitis.

PMID- 18090235
TI  - Hereditary pancreatitis amlodipine trial: a pilot study of a calcium-channel
      blocker in hereditary pancreatitis.
AB  - OBJECTIVES: Hereditary pancreatitis (HP) is a form of recurrent acute
      pancreatitis (AP) mediated by mutations in cationic trypsinogen (PRSS1).
      Mutations cluster in the calcium-associated regulator regions of PRSS1. In rats,
      calcium-channel blockers (CCB) prevent hyperstimulation-associated AP. Because of
      the potential importance of hyperstimulation in triggering episodes of AP in HP,
      we designed a pilot study to evaluate the safety and potential benefit of CCB use
      in HP. METHODS: Subjects 6 years or older had a PRSS1 mutation, recurrent AP, and
      pain. Total study duration was 16 weeks. Amlodipine was given during weeks 0 to
      11. Dose (2.5, 5, or 10 mg) was based on weight (range, 0.08-0.17 mg x kg(-1) x
      d(-1)). Subjects filled a daily diary including pain (0-10 scale) and blood
      pressure reading. Clinical assessments occurred at weeks -4, 0, 1, 2, 6, 10, 11,
      and 12. Subjects filled a Medical Outcomes Study Short-Form Survey version 2 (SF
      10 for children <14 years old) at weeks -4, 0, 6, and 10. Data were compared for
      weeks -4 to 0 and 6 to 10. RESULTS: Nine subjects signed informed consent (4
      males; 12-52 years old). Four were excluded during the screening phase. Drug was
      discontinued in one due to development of unilateral lower-extremity numbness.
      Four subjects (12-31 years old) completed the study. Mean blood pressure,
      laboratory tests, physical findings, and daily pain scores did not clinically
      significantly differ before and during drug therapy, but all reported reduced
      symptoms. Three reduced analgesic use. Three had improved scores on the Medical
      Outcomes Study Short-Form Survey version 2. CONCLUSIONS: Amlodipine is generally
      safe in subjects with HP and does not increase pain or episodes of AP. Further
      research into the mechanism of CCB on pancreatitis would be important to provide
      a pathophysiologic basis to support further trials in HP.

PMID- 18090236
TI  - Evaluation of pancreatic exocrine secretion using 13C-dipeptide (benzoyl-L
      tyrosyl-[1-(13)C]alanine) breath test: focusing on pancreatoduodenectomy cases.
AB  - OBJECTIVES: We investigated whether a breath test using benzoyl-L-tyrosyl-[1
      (13)C]alanine (Bz-Tyr-Ala) allows assessment of pancreatic exocrine function.
      METHODS: Benzoyl-L-tyrosyl-[1-(13)C]alanine was orally administered, and changes
      in (13)CO2 were expressed as delta per thousand. The breath test was performed in
      chronic pancreatitis patients and healthy subjects in a preliminary study and,
      subsequently, in 17 pancreatoduodenectomy patients, to examine the difference
      between the results obtained at the times of pancreatic tube insertion and
      removal, the relationship between breath test results after tube removal and the
      volume of pancreatic juice drained, and the difference in results between the
      presence versus the absence of histological changes of chronic pancreatitis.
      RESULTS: The delta per thousand was lower in the chronic pancreatitis patients
      than in healthy subjects. In the postoperative patients, the delta per thousand
      was higher at tube insertion than at tube removal. The correlations of the delta
      per thousand with the maximum volume of pancreatic juice, its mean volume, and
      pancreatic juice amylase levels were 0.865, 0.757, and 0.853, respectively. The
      delta per thousand was lower in 11 patients with that in 6 patients without
      histological changes of chronic pancreatitis. CONCLUSIONS: These results suggest
      that the Bz-Tyr-Ala breath test can measure pancreatic exocrine function.

PMID- 18090237
TI  - Smoking cessation at the clinical onset of chronic pancreatitis and risk of
      pancreatic calcifications.
AB  - OBJECTIVE: Cigarette smoking is associated with a higher risk of developing
      chronic pancreatitis (CP) and increases the likelihood of developing pancreatic
      calcifications. The aim of this study was to know whether smoking cessation
      modifies the course of the disease. METHODS: Patients with CP who had been
      followed up for more than 6 years from clinical onset and who had not developed
      calcifications after 5 years were analyzed. We studied smokers, never-smokers,
      and patients who had given up smoking within 5 years. For actuarial analysis, the
      sixth year was considered as time 0. RESULTS: Of the 360 patients, there were 43
      women and 317 men (88.1%) with a mean age of 38.7 years. The median follow-up was
      19.0 years. Chronic pancreatitis was alcohol-associated in 255 patients,
      hereditary in 10, obstructive in 54, and idiopathic in 41. There were 317 smokers
      (88.1%) and 259 alcohol drinkers (71.9%). At the end of the follow-up, 212
      patients (59.8%) developed calcifications. Concerning the risk of calcifications,
      never-smokers and ex-smokers had similar actuarial curves, and these were
      significantly different from the curve for smokers (P < 0.003). Considering never
      smokers as the reference class, ex-smokers had an odds ratio (OR) of 0.56 (95.0%
      confidence interval [CI], 0.2-1.4; P = not significant), patients smoking 1 to 10
      cigarettes per day had an OR of 1.95 (95.0% CI, 1.1-3.4; P < 0.019), patients
      smoking 11 to 20 cigarettes per day had an OR of 1.76 (95.0% CI, 1.1-2.8; P <
      0.0018), and those smoking more than 20 cigarettes per day had an OR of 1.79
      (95.0% CI, 1.1-2.9; P < 0.019). Alcohol cessation seems to have no influence.
      CONCLUSIONS: Smoking cessation in the first years from the clinical onset of CP
      reduces the risk of developing pancreatic calcifications.

PMID- 18090238
TI  - Serum immunosuppressive acidic protein levels in patients with severe acute
      pancreatitis.
AB  - OBJECTIVES: In severe acute pancreatitis (SAP), immunologic impairment in the
      early phase may be linked to subsequent infectious complications.
      Immunosuppressive acidic protein (IAP) is an immunosuppressive factor to be
      present in serum and ascites of cancer patients, and it is used as a tumor marker
      and an index of immune status of cancer hosts. METHODS: We measured serum IAP
      levels in 42 patients with SAP (Japanese severity score [JSS] > or = 2) on
      admission and analyzed the relationships with disease severity, pancreatic
      necrosis, blood biochemical parameters on admission, and clinical outcome
      (infection and death). RESULTS: Serum IAP level increased 791 +/- 285 microg/mL
      (range, 159-1430 microg/mL) on admission and recognized abnormal high level
      (normal range, < 500 microg/mL) in 37 patients (88.1%). Serum IAP level was
      significantly lower in patients of stages 3 and 4 (JSS > or = 9) (678 +/- 187
      microg/mL) than that in patients of stage 2 (2 < or = JSS < or = 8) (848 +/- 311
      microg/mL). It was also significantly lower in patients whose Ranson score was 5
      or higher (674 +/- 287 microg/mL) than that in patients whose Ranson score was 4
      or less (910 +/- 287 microg/mL). Moreover, it was significantly lower in patients
      with pancreatic necrosis (693 +/- 194 microg/mL) than that in patients without
      pancreatic necrosis (922 +/- 336 microg/mL). Among the blood biochemical
      parameters on admission, serum IAP was significantly negatively correlated with
      hematocrit, serum lipase, and serum interferon gamma and was significantly
      positively correlated with serum total protein. Serum IAP levels in patients of
      stage 2 reached higher peak at 7 days after admission and decreased more rapidly
      than those in patients of stages 3 and 4. CONCLUSIONS: Serum IAP levels were
      elevated in patients with SAP but were significantly lower in patients with
      higher grade of severity or pancreatic necrosis. These results suggest that serum
      IAP levels may be related to systemic inflammatory response and reflect the
      immunoresponsiveness in patients with SAP.

PMID- 18090239
TI  - Protein expression profiling reveals distinctive changes in serum proteins
      associated with chronic pancreatitis.
AB  - OBJECTIVE: Testing of serum for protein patterns to monitor progression of
      suspected to definite chronic pancreatitis (CP). METHODS: Serum samples of CP
      patients and healthy volunteers were fractionated on anion exchange columns and
      analyzed by surface-enhanced laser desorption/ionization-time-of-flight mass
      spectrometry to elucidate CP-related protein alterations and to identify
      biomarkers for this disease. Potential biomarkers were purified and identified by
      mass spectrometry. RESULTS: In total, 258 protein peaks were found that
      discriminated between the 2 groups. Analysis revealed 28 most prominent peaks on
      immobilized metal affinity capture coupled with Cu and CM10 protein chips,
      covering the m/z range between 3.3 and 33.3 kd. Performing multivariate pattern
      analysis, the best pattern model was obtained using fraction 6 on immobilized
      metal affinity capture coupled with Cu arrays with a sensitivity of 96% and a
      specificity of 84%. Using a combination of matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry and immunodepletion, we identified 14
      m/z peaks. The proteins were found to be significantly decreased in CP serum and
      were identified as retinol-binding protein, serum amyloid-alpha, apolipoprotein A
      II (Apo A-II), Apo C-I, Apo C-II, Apo C-III, and transthyretin and truncated
      forms thereof. CONCLUSIONS: Distinct protein profile differences exist between
      normal and CP serum and reflect the metabolic and inflammatory condition in CP
      patients. The identified protein panel may eventually serve as a diagnostic
      marker set for CP.

PMID- 18090240
TI  - Decreased insulin secretion and insulin sensitivity are associated with liver
      function in subjects with fasting glucose between 100 and 109 mg/dL in Taiwanese
      population.
AB  - OBJECTIVE: In 2003, the American Diabetes Association recommended that the lower
      limit for the diagnosis of impaired fasting glucose (IFG) should be reduced from
      110 to 100 mg/dL in the analysis of the associated risk factors of IFG. It has
      been proposed that liver dysfunction may contribute to the development of type 2
      diabetes. A primary aim was to investigate the relationship between liver enzyme
      and insulin resistance (IR) in IFG group. The secondary aim was to investigate IR
      and beta-cell function assessed by homeostasis model assessment (HOMA-IR and HOMA
      %B, respectively) in subjects with fasting plasma glucose (FPG) between 100 and
      109 mg/dL. METHODS: We enrolled 284 subjects whose medical history and physical
      examination required tests to screen for metabolic abnormalities. In addition, we
      also excluded all factors affecting glucose or insulin metabolism. According to
      the FPG level, they were divided into the following groups: group A, FPG < 100
      mg/dL; group B, FPG = 100 to 109 mg/dL; group C, FPG = 110 to 125 mg/dL. RESULTS:
      Group B as compared with group A had significant increase of HOMA-IR and decrease
      of HOMA-%B. Among the whole population, the fasting insulin level, the fasting
      glucose, HbA1c, HOMA-IR, alanine aminotransferase, gamma-glutamyltranspeptidase,
      aspartate aminotransferase, and the diastolic blood pressure all increased
      significantly as the glycemic status progressed, whereas HOMA-%B levels decreased
      significantly as the glycemic status progressed. The lipid profile, alkaline
      phosphatase, and systolic blood pressure did not differ significantly among 3
      different glycemic classifications. CONCLUSIONS: Study results indicate that,
      first, there was a significant decrease of insulin sensitivity and insulin
      secretion in subjects with fasting glucose from 100 to 109 mg/dL compared with
      subjects with normal fasting glucose. Second, alanine aminotransferase, aspartate
      aminotransferase, and gamma-glutamyltranspeptidase were associated with IR as the
      glycemic status progressed in the IFG group.

PMID- 18090241
TI  - Characteristic clinicopathological features of the types of intraductal papillary
      mucinous neoplasms of the pancreas.
AB  - OBJECTIVES: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas
      encompasses a spectrum of neoplasms with both morphological and
      immunohistochemical variations of mucin glycoproteins. Recently, a consensus
      nomenclature and criteria were histologically defined for classifying these
      variants of IPMNs into gastric, intestinal, pancreatobiliary, and oncocytic
      types. The purpose of this study was to determine associations between the
      histological types and clinicopathological features in patients with IPMN.
      METHODS: Sixty-one patients with IPMN operated upon at Tohoku University Hospital
      between 1988 and 2006 were retrospectively analyzed. RESULTS: Our series included
      27 gastric-, 29 intestinal-, 4 pancreatobiliary-, and 1 oncocytic-type IPMNs.
      Statistically, the types of IPMN were significantly associated with the
      histological diagnoses, macroscopic types, and survival of the patients.
      Characteristically, the gastric-type IPMNs were likely to be diagnosed as benign,
      to be confined to branch ducts, and to have fair prognoses. On the other hand,
      the intestinal-type IPMNs were likely to be diagnosed as malignant, occupy the
      main duct, and have poor prognoses. Because of the small number of
      pancreatobiliary-type IPMNs and only 1 case of oncocytic-type IPMN, we were
      unable to determine any of their clinicopathological characteristics in our
      series. CONCLUSIONS: Evaluation of the histological types of IPMN may help to
      predict the clinical course of patients with IPMN and to design improved clinical
      management for these patients.

PMID- 18090242
TI  - Expression of transforming growth factor beta by small duct epithelium in
      chronic, cancer-associated, obstructive pancreatitis: an in situ hybridization
      study and review of the literature.
AB  - OBJECTIVES: Transforming growth factor beta (TGF-beta) is a dominant mediator of
      pancreatic fibrosis. The objective of this study was to identify cellular sources
      of TGF-beta mRNA and compare the results with previous immunohistochemical/in
      situ hybridization studies. METHODS: In situ hybridization of TGF-beta was
      conducted for 9 human tissues of chronic obstructive pancreatitis (COP) and 2
      control specimens. By classifying these 9 COP tissues into 3 fibrosis phases by
      the amount of fibrotic space, histopathologic changes were examined for each
      fibrosis phase. Whether or not TGF-beta-positive cells were closely distributed
      to fibrosis was also investigated in control and COP cases. RESULTS: Three cases
      were categorized in early, intermediate, and advanced stages of fibrosis.
      Transforming growth factor beta mRNA was identified for a part of small duct
      epithelia, that is, intercalated ductule cells, centroacinar cells, and/or
      metaplastic ductal structures adjacent to acinar cells. The number of TGF-beta
      positive cells was greater in COP cases than in controls. In controls and in the
      early stage of fibrosis, no fibrosis was seen near TGF-beta-positive cells.
      CONCLUSIONS: Small duct epithelia are the main cellular sources of TGF-beta in
      COP, and many of them may be working for COP fibrosis either directly or
      indirectly.

PMID- 18090243
TI  - Surgical treatment of pancreatic serous cystadenoma: aggressive for operations
      but limited resections.
AB  - OBJECTIVE: Serous cystadenomas of the pancreas are being increasingly identified
      as the advancement of the diagnostic abdominal imaging. However, the optimal
      timing of surgical intervention for this disease remains controversial. METHODS:
      A total of 44 patients presenting with serous cystadenoma of the pancreas from
      1981 to 2006 were identified. The patients were divided into 3 groups,
      nonoperated, operated without correct preoperative diagnosis, and operated with
      correct preoperative diagnosis. The tumor characteristics, preoperative symptoms,
      operative procedures, morbidity, mortality, tumor recurrences, and postoperative
      life quality are compared. RESULTS: Nine patients did not receive operation
      because of high surgical risks or no presenting symptoms. Fourteen patients
      received operation under correct preoperative diagnosis, and 21 patients received
      operation under incorrect preoperative diagnosis. In the group with correct
      preoperative diagnosis, the average tumor size was 5.4 cm, 5 patients had
      preoperative symptoms, and 4 patients received limited resection. In the group
      without correct preoperative diagnosis, the average tumor size was 4 cm, 11
      patients had preoperative symptoms, and 3 patients underwent limited resection.
      All patients are satisfied with the quality of life postoperatively. No patients
      have tumor recurrences during follow-ups. CONCLUSIONS: Unless the diagnosis of
      serous cystadenoma is certain, all cystic tumors should be resected if operative
      risks are acceptable. The procedures should be as limited as possible if no
      evidence of malignancy is noted preoperatively.

PMID- 18090244
TI  - Functional and morphological changes in pancreatic remnant after
      pancreaticoduodenectomy.
AB  - OBJECTIVES: Pancreatic exocrine insufficiency has been reported to be more common
      in pancreaticogastrostomy (PG) than in pancreaticojejunostomy (PJ) after
      pancreaticoduodenectomy (PD). This study aimed to evaluate the long-term outcome
      after PD between these 2 groups. METHODS: We evaluated the long-term functional
      status of 42 surviving patients diagnosed with periampullary lesions who
      underwent PJ or PG after PD and followed up for more than 1 year. Among these, 23
      patients underwent PJ and 19 patients underwent PG. To compare the 2 groups, we
      analyzed the (1) pancreatic exocrine insufficiency by questioning the presence or
      absence of steatorrhea, (2) pancreatic endocrine function by measuring
      glycohemoglobin A1c, fasting blood glucose, and history of new-onset diabetes,
      (3) nutritional status by measuring serum total protein, albumin, cholesterol,
      and triglyceride, (4) gastric emptying time, (5) panendoscopic findings, (6)
      changes of pancreatic duct diameter by computed tomography, and (7) relaparotomy
      rate. RESULTS: The mean follow-up time for PG and PJ were 37 +/- 23 and 103 +/-
      52 months, respectively (P < 0.05). A total of 52.4% patients developed
      pancreatic exocrine insufficiency, and 11.9% had new-onset diabetes. There was no
      significant difference between PJ and PG groups. A significantly improved
      postoperative nutritional state regarding serum total protein and albumin were
      noticed in both groups. There was no significant difference in terms of gastric
      emptying time, positive panendoscopic findings, and changes in pancreatic duct
      diameter. The pancreatic remnant-related relaparotomy rate was higher in the PJ
      group as compared with the PG group (17.4% vs 0%; P = 0.056). CONCLUSIONS: There
      is no significant difference in pancreatic exocrine or endocrine insufficiency,
      gastric emptying time, and positive panendoscopic findings between PJ and PG.
      Pancreaticojejunostomy was associated with a higher pancreatic remnant-related
      relaparotomy rate; however, because of a shorter follow-up in the PG group, a
      continuous long-term follow-up is still needed.

PMID- 18090245
TI  - Allopurinol in rat chronic pancreatitis: effects on pancreatic stellate cell
      activation.
AB  - OBJECTIVES: Activation of pancreatic stellate cells (PSCs) is a key event in
      pancreatic fibrosis. Xanthine oxidase-derived free radicals are involved in the
      mechanism of chronic pancreatitis (CP). We here searched the in vivo effects of
      allopurinol on PSC activation and its relation to tissue oxidative stress and
      histological findings in rat CP. METHODS: Rat CP was induced with intraductal
      trinitrobenzene sulfonic acid in groups 1 (n = 16) and 2 (n = 10). Group 3 (n =
      10) received intraductal saline. Four weeks after induction, group 1 received
      allopurinol (200 mg/kg, s.c.), and groups 2 and 3 received saline. After 4 weeks,
      oxidative stress parameters, histological evaluation, and immunostaining for
      alpha-smooth muscle actin (+) PSCs were performed in the pancreata. RESULTS:
      Oxidative stress parameters improved significantly in group 1 compared with
      groups 2 and 3. Collagen deposition and lobular/sublobular atrophy were
      significantly lower in group 1 than in group 2. Alpha-smooth muscle actin (+)
      PSCs counts in group 1 were significantly lower than in group 2, and were in
      correlation with the degree of fibrosis and atrophy. CONCLUSIONS: Allopurinol
      inhibits PSC activation in vivo. Pancreatic fibrosis can be prevented, at least
      in part, by antioxidant treatment through xanthine oxidase metabolism. Long-term
      use of allopurinol and its analogs may be considered in clinical trials with CP.

PMID- 18090246
TI  - Indium-111 pentetreotide uptake by pancreatic polypeptide cell hyperplasia:
      potential pitfall in somatostatin receptor scintigraphy.
AB  - A 71-year-old man with duodenal gastrin cell tumor was being evaluated for
      residual/metastatic disease. Somatostatin receptor scintigraphy (SRS) identified
      a 2-cm area of focal uptake within the head of the pancreas, consistent with a
      pancreatic neuroendocrine tumor. Pathological examination did not reveal any
      malignancy within the pancreas. Instead, the pancreatic head showed pancreatic
      polypeptide cell hyperplasia. Strong and diffuse immunoreactivity to somatostatin
      receptor 2A antibody by immunoperoxidase staining confirmed that the lesion
      correlated with the site of radioactive tracer (Indium-111 pentetreotide) uptake
      seen on SRS. The current report therefore presents pancreatic polypeptide cell
      hyperplasia as a new pitfall in SRS.

PMID- 18090247
TI  - Nasojejunal feeding in patients with severe acute pancreatitis: comparison of
      endoscopic and self-migration tube placement.

PMID- 18090248
TI  - Is autoimmune pancreatitis a risk factor for pancreatic cancer?

PMID- 18090249
TI  - Lactate dehydrogenase-to-lymphocyte ratio for the prediction of infection in
      acute necrotizing pancreatitis.

PMID- 18090250
TI  - Hyperlipasemia/pancreatitis in adults with dengue hemorrhagic fever.

PMID- 18090251
TI  - Castleman disease imitating pancreatic tumor presenting with pericardial and
      pleural effusion.

PMID- 18090252
TI  - Autoimmune pancreatitis in the setting of Castleman disease.

PMID- 18090257
TI  - Endoscopic drainage of a superiorly based subperiosteal orbital abscess.

PMID- 18090258
TI  - p75NTR and sortilin increase after facial nerve injury.
AB  - OBJECTIVES: After axotomy, Schwann cells (SCs), required for successful nerve
      regeneration, undergo a number of cellular changes including dedifferentiation,
      proliferation, expression of molecules that support axon growth, and apoptosis.
      This study investigated the role of p75, sortilin, and proneurotrophins in SC
      survival after facial nerve (FN) axotomy. STUDY DESIGN: Preliminary animal study.
      METHODS: With use of FN SCs, expression of p75 and its coreceptor sortilin were
      quantified by immunofluorescence on days 12, 22, and 52 after axotomy in vivo and
      by Western blot in vitro. Contralateral FNs served as a control. SC apoptosis was
      detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).
      To verify a causative role for p75 in FN SC death, cultured FN SCs were treated
      with pro-nerve growth factor (NGF), and apoptosis was determined by TUNEL.
      RESULTS: Expression of p75 and sortilin increased in FN SCs distal (P < .05) to
      the axotomy compared with the contralateral controls for all time points. SC
      apoptosis also significantly increased in the distal segment compared with the
      contralateral and proximal portions (P < .05). ProNGF, a p75 ligand, increased
      apoptosis and p75 expression in primary FN SC cultures. CONCLUSION: FN axotomy
      increases p75 and sortilin expression in SCs, which correlates with increased
      apoptosis. These findings suggest roles for p75 and sortilin in SC loss after FN
      injury. Sortilin is a novel target in promoting FN healing after injury.

PMID- 18090259
TI  - Correction of progressive hearing loss in superior canal dehiscence syndrome.
AB  - A 44-year-old woman presented with typical vestibular symptoms of superior
      semicircular canal dehiscence syndrome (SSCDS). In addition, the patient
      experienced a rapidly progressive mixed hearing loss in the affected ear prior to
      surgical intervention that was unresponsive to oral steroid administration.
      Following middle fossa craniotomy with repair of the dehiscence, the patient's
      mixed hearing loss resolved to normal levels with no air-bone gap. In this
      report, we discuss the possible etiology of this rapidly progressive hearing loss
      and its implications on the differential diagnosis of patients with new onset
      mixed hearing losses. We also contrast the index case of progressive mixed loss
      with the more frequent conductive hearing loss seen in SSCDS.

PMID- 18090260
TI  - Educational and research horizons in laryngology.

PMID- 18090261
TI  - Modified retrograde approach to upper eyelid static loading.
AB  - OBJECTIVES/HYPOTHESIS: Upper eyelid static weight loading is a technique commonly
      used to treat paralytic lagophthalmos. The traditional approach using the
      pretarsal crease incision leads to interruption of the anterior levator muscle
      fibers that attach to the face of the tarsus at its upper two thirds. This
      disruption can lead to permanent upper eyelid blepharoptosis. The retrograde
      approach avoids this problem but results in an incision at the lid margin, the
      dependent aspect of the weight. This increases the risk of implant extrusion. We
      hypothesize that a newly described modified retrograde approach is a safe and
      effective approach that avoids the pitfalls of previously described techniques.
      STUDY DESIGN: Retrospective review. METHODS: Eight patients were evaluated with
      preoperative and 3 to 6 month postoperative photographs with the eyes in the open
      and closed positions for the degree of lagophthalmos and blepharoptosis present.
      Patients were also evaluated for development of complications such as implant
      extrusion, pain, or infection. The surgical technique uses a supratarsal skin
      crease incision, supramuscular dissection to the lid margin, entry into the
      tarsal plane at its inferior-most aspect, creation of a pocket for implant
      insertion, and layered closure. RESULTS: All patients had complete correction of
      lagophthalmos. No patients experienced infection, extrusion, or eye pain after
      surgery. All patients had less than 2-mm ptosis after surgery, with no patients
      experiencing any visual field disruption. CONCLUSIONS: The modified retrograde
      approach to upper eyelid static loading for paralytic lagophthalmos provides
      advantages over other techniques described. It is a safe, efficacious procedure,
      well tolerated by patients.

PMID- 18090262
TI  - Social aspects of antiretroviral therapy scale-up: introduction and overview.

PMID- 18090263
TI  - Beyond the numbers: using rights-based perspectives to enhance antiretroviral
      treatment scale-up.
AB  - Human rights analyses, concepts, and in particular rhetoric have played a
      consistent role in the global response to HIV for over two decades. Despite the
      longstanding recognition of human rights as essential to an effective response,
      recent global guidance, particularly with respect to the implementation of
      antiretroviral treatment (ART) scale-up efforts, falls short of meaningfully
      incorporating human rights norms and concepts. Applying human rights to ART scale
      up draws attention to who is gaining access to ART, how they are gaining access,
      and over what period of time, not just how many people gain access. Deliberate
      consideration of the human rights principles of the interdependence of rights
      (including attention to the legal and policy environment), participation, non
      discrimination, accountability, and key aspects of the right to health can help
      to identify and overcome some of the challenges to increasing and sustaining
      access to treatment and needed services, as well as to promote accountability and
      transparency for what is done and how it is done. Whereas a need remains to
      document evidence of the ways in which a lack of attention to human rights
      negatively influences the long-term outcomes of scale-up programmes, this paper
      focuses on the positive role human rights can play in ART scale-up efforts, and
      offers suggestions for research and action moving forward.

PMID- 18090264
TI  - Gender, sexuality, and antiretroviral therapy: using social science to enhance
      outcomes and inform secondary prevention strategies.
AB  - OBJECTIVES: To explore how, within the context of antiretroviral therapy (ART)
      uptake and adherence, social science research on gender and sexuality could
      complement existing epidemiological and behavioral research on uptake, adherence,
      disinhibition and reproduction. METHODS: Bibliographical database searches on ART
      uptake and adherence, the sexual practices of HIV-positive individuals, and
      fertility management among HIV-positive men and women were conducted over a 6
      month period using ISI Web of Science and Medline. Articles were sorted by main
      topic and then analysed to reveal the unarticulated assumptions that have framed
      research to date. RESULTS: The adoption of more social scientific theoretical
      frameworks would move research on uptake, adherence, disinhibition, and
      reproduction among HIV-infected and affected individuals beyond the current
      overemphasis on how cognitive and ideological factors shape behavior and towards
      an understanding of how culture and inequality shapes the way people engage with
      ART and craft their sexual and reproductive lives. Research that pays greater
      attention to the social processes that create differentials in uptake and
      adherence, rather than just the quantification of those differentials, will open
      up new possibilities for community-based interventions. Similarly, social science
      research on gender and sexuality can provide insight into the social factors
      shaping reproductive and sexual behavior, and thus enhance our ability to manage
      the potentially competing priorities of limiting marital sexual risk and
      increasing access to reproductive choice among HIV-affected couples. CONCLUSION:
      The ability to produce good clinical outcomes and to develop effective policies
      for secondary prevention will be enhanced by a deeper understanding of how gender
      inequality and the social organization of sexuality shape the sexual and
      reproductive behavior of individuals using ART.

PMID- 18090265
TI  - Adherence as therapeutic citizenship: impact of the history of access to
      antiretroviral drugs on adherence to treatment.
AB  - A dramatic increase in the use of antiretroviral drugs in Africa has increased
      focus on adherence to treatment, which has so far been equivalent if not superior
      to that in northern contexts. The reasons for this exceptional adherence are
      poorly understood. In this paper, we examine adherence in the historical and
      ethnographic context of access to treatment in Burkina Faso, Cote d'Ivoire and
      Mali. Living where there is no social security and minimal, if any, medical care,
      individuals diagnosed with HIV are faced with the threat of illness, death,
      ostracism and destitution, and were obliged to negotiate conflicting networks of
      obligation, reciprocity, and value. HIV and AIDS programmes value efforts to
      address social, and indeed biological, vulnerability. In contrast, kinship-based
      social relationships may value individuals in other ways. These conflicting moral
      economies often intersect in the worlds of people living with HIV. HIV status can
      be used to claim resources from the public or non-governmental organization
      programmes. This may interfere with social networks that are the most stable
      source of material and emotional support. Self-help and empowerment techniques
      provided effective tools for people living with HIV to fashion themselves into
      effective advocates. In the early years of the use of antiretroviral therapy
      (ART), access to treatment was thus mediated by confessional practices and forms
      of social triage. We introduce the term 'therapeutic citizenship' to describe the
      way in which people living with HIV appropriate ART as a set of rights and
      responsibilities to negotiate these at times conflicting moral economies.
      Exemplary adherence should be viewed through the lens of therapeutic citizenship.

PMID- 18090266
TI  - Life projects and therapeutic itineraries: marriage, fertility, and
      antiretroviral therapy in Nigeria.
AB  - OBJECTIVE: To examine and understand the marital and fertility aspirations and
      behaviours of individuals receiving antiretroviral therapy (ART) in Nigeria and
      evaluate the effects on sexual behaviour, disclosure, and adherence. DESIGN AND
      METHODS: The study used ethnographic methods of participant observation and in
      depth interviews of individuals receiving ART through a government-supported
      programme in southeastern Nigeria. RESULTS: Interviews and observations of
      individuals on treatment demonstrate that marriage and childbearing are paramount
      desires for people whose health is restored by ART. The concept of life projects
      is introduced and combined with the established idea of therapeutic itineraries
      to show how participation in and adherence to treatment, disclosure of HIV
      status, and decisions about sexual behaviour cannot be understood in purely
      biomedical terms. Marital and reproductive aspirations routinely impinge on and
      often trump clinical and public health priorities. Emblematic case studies are
      provided to illustrate the social dynamics that motivate and explain behaviour
      seemingly inimical to individual and public health. CONCLUSION: Effective
      antiretroviral programme design and therapy management will require acknowledging
      and often enabling rather than discouraging the marital and reproductive goals of
      individuals if issues of disclosure, adherence, and prevention are to be
      realistically addressed.

PMID- 18090267
TI  - Scale-ups, scarcity, and selections: the experience of doctors in South Africa.
AB  - OBJECTIVES: To present the ethical and clinical experience of public sector
      physicians during the post-Apartheid period in South Africa, who were faced with
      poverty, medical scarcity and unexpected government resistance in treating
      individuals with HIV infection. METHODS: Oral history interviews with 73
      physicians from major cities, mine company clinics, and rural hospitals selected
      because of their long-standing commitment to treating people with AIDS.
      CONCLUSION: The onset of the government's 'rollout' of antiretroviral therapy
      (ART) in 2003, providing drugs to public sector patients, has not put an end to
      the rationing of care that characterised the pre-ART period. Subsequently, rules
      were established to guide such rationing in an equitable fashion. But there are
      occasions when doctors override their own rules, demonstrating the complex
      interplay between principles of equity and the claims of moral duty to patients,
      especially in instances of life and death.

PMID- 18090268
TI  - Sexuality, reproduction, and HIV in women: the impact of antiretroviral therapy
      in elective pregnancies in Cuba.
AB  - OBJECTIVE: Since HIV was first diagnosed in Cuba in 1985 to the end of 2006, 246
      HIV-positive women have given birth to 266 children; of these, more than half
      were born after 2001, when antiretroviral therapy (ART) became widely available
      in Cuba. The objective of the study was to explore how the provision of ART free
      at point of delivery to all clinically indicated patients might be related to the
      rapid increase in pregnancies in HIV-positive women. DESIGN: : A qualitative
      instrument was designed to assess how reproductive and sexual histories were
      affected by a diagnosis of HIV and by the availability of ART. METHODS: Data were
      collected from 55 women, representing 26% of HIV-positive women who are known to
      have given birth in Cuba. A structured interview was used to collect qualitative
      information on women's reproductive and sexual histories. RESULTS: Sixty-four per
      cent of women interviewed reported becoming pregnant aware of their HIV status or
      that of their partner; of these, all except one became pregnant after ART became
      widely available in Cuba. The majority said their worries about transmitting HIV
      subsided after talking to doctors, obtaining information on mother-to-child
      transmission, learning they could receive ART and deliver by Cesarean section to
      reduce the risk of vertical transmission significantly, and meeting HIV-positive
      women who had HIV-negative children. CONCLUSION: The introduction of effective
      therapy for HIV, by transforming the social and clinical course of HIV/AIDS and
      allowing the possibility of having HIV-negative children, contributes to decrease
      HIV/AIDS-related fear and stigma and reshape reproduction.

PMID- 18090269
TI  - Hope: a new way to look at the HIV epidemic.
AB  - There is currently a shift towards embracing 'structural intervention' approaches
      in HIV prevention and HIV treatment. We offer the concept of hope as an important
      new framework for researching HIV prevention and HIV treatment. We argue first,
      that hope is linked to capacity for behaviour change and helps us understand how
      social environments enable as well as constrain risk reduction. Second, we argue
      that hope helps us understand HIV treatment engagement and impact, especially
      uneasy relations between treatment access expectation and the lived experience of
      treatment delivery in environments characterized by fragile treatment systems. We
      conclude that HIV prevention should seek to create the structural conditions
      conducive to sustaining hope in the future, while drawing attention to the often
      unforeseen local effects of global discourses of HIV treatment promise which may
      offer an illusion of hope in certain contexts. We draw specific attention to the
      urgent need for interventions to tackle the adverse psychological and social
      consequences of fragile treatment delivery. Hope is an under researched concept
      in the social science of HIV prevention and HIV treatment. It offers unrealized
      potential, particularly for thinking about structural interventions in relation
      to managing HIV as a chronic illness and for maximizing HIV risk reduction in
      resource-poor settings.

PMID- 18090270
TI  - Long-term psychosocial challenges for people living with HIV: let's not forget
      the individual in our global response to the pandemic.
AB  - Since the beginning of the HIV epidemic, people living with HIV have faced
      numerous psychological and behavioral challenges. With the advent of
      antiretroviral therapy (ART) there have been dramatic shifts in some of these key
      challenges and new ones have come to the forefront. This paper highlights several
      critical psychological and behavioral aspects of HIV disease, a few of which
      require focused attention, including mental health, stigma and disclosure,
      adherence, and sexual behavior. Although the focus is primarily on adults living
      with HIV, we also comment on some of the additional challenges for children and
      young people. Our critical examination in these areas draws upon the lessons
      learned in contexts in which ART has been available for a decade, and we explore
      what is currently happening in settings with more recent treatment access. In the
      end we offer our insights into what we may expect in the future, and provide
      recommendations for ongoing prevention and care initiatives with adults,
      children, and young people affected by this disease.

PMID- 18090271
TI  - Scale-up of HIV care and treatment: can it transform healthcare services in
      resource-limited settings?
AB  - The rapid expansion of HIV care and treatment in resource-limited settings will
      undoubtedly ameliorate conditions in communities ravaged by this epidemic around
      the world and enable persons living with HIV to live longer, more productive
      lives. Concerns have been raised, however, regarding the possible deleterious
      effects on other health services. This paper argues that efforts to scale up HIV
      care and treatment in resource-limited countries, if designed and implemented
      with the additional goal of achieving broad health benefits, may serve as a
      catalyst for the establishment of more effective and responsive health systems.
      In order to determine these broader effects, mechanisms need to be established
      that enable relevant research and evaluation questions to be answered.

PMID- 18090273
TI  - A strategy for accelerating the development of preventive AIDS vaccines.

PMID- 18090274
TI  - Elevated expression of activation induced cytidine deaminase in peripheral blood
      mononuclear cells precedes AIDS-NHL diagnosis.
AB  - Non-Hodgkin's B cell lymphoma (NHL) is a common cancer in HIV infection. Many NHL
      are thought to result from errors in class switch recombination and/or somatic
      hypermutation, processes that occur in germinal center B cells, and require the
      activity of activation induced cytidine deaminase (AID). Since NHL is a common
      cancer in HIV infection, and expression of AID could contribute to the
      development of NHL, we hypothesized that AID expression would be elevated in
      those who went on to develop AIDS-associated NHL (AIDS-NHL). AID mRNA levels were
      measured by TaqMan RT-PCR in peripheral blood mononuclear cells, obtained prior
      to AIDS-NHL diagnosis, from 16 HIV-infected subjects who developed AIDS-NHL, and
      from control subjects (AIDS but no NHL, and HIV-negative subjects). PBMC AID
      expression was markedly elevated in those who developed AIDS-NHL, when compared
      to AIDS and HIV-negative controls. Additionally, AID expression was seen to
      differ depending on NHL subtype, with the highest levels of expression seen in
      those who developed Burkitt's lymphoma.

PMID- 18090275
TI  - Long-term HIV-1 infection of neural progenitor populations.
AB  - BACKGROUND: HIV can reside in the brain for many years. While astrocytes are
      known to tolerate long-term HIV infection, the potential of other neural cell
      types to harbour HIV is unclear. OBJECTIVE: To investigate whether HIV can
      persist in neural progenitor cell populations. DESIGN: A multipotent human neural
      stem cell line (HNSC.100) was used to compare HIV infection in neural progenitor
      and astrocyte cell populations. METHODS: Expression of cellular genes/proteins
      was analysed by real-time reverse transcriptase PCR, Western blot,
      immunocytochemistry and flow cytometry. Morphological properties of cells were
      measured by quantitative fluorescent image analysis. Virus release by cells
      exposed to HIV-1IIIB was monitored by enzyme-linked immunosorbent assay for Gag.
      Proviral copy numbers were determined by real-time PCR and early HIV transcripts
      by reverse transcriptase PCR. Rev activity was determined with a fluorescent
      based reporter assay. RESULTS: Progenitor populations differed from astrocyte
      populations by showing much lower glial fibrillary acidic protein (GFAP)
      production, higher cell-surface expression of the CXCR4 chemokine receptor,
      higher Rev activity and distinct cell morphologies. HIV-exposed progenitor
      cultures released moderate amounts of virus for over 2 months and continued to
      display cell-associated HIV markers (proviral DNA, early HIV transcripts) during
      the entire observation period (115 days). Differentiation of HIV-infected
      progenitor cells to astrocytes was associated with transient activation of virus
      production. Long-term HIV infection of progenitor populations led to upregulation
      of GFAP and changes in cell morphology. CONCLUSION: These studies suggest that
      neural progenitor populations can contribute to the reservoir for HIV in the
      brain and undergo changes as a consequence of HIV persistence.

PMID- 18090276
TI  - Reduced mortality and CD4 cell loss among carriers of the interleukin-10 -1082G
      allele in a Zimbabwean cohort of HIV-1-infected adults.
AB  - OBJECTIVES: To evaluate the effect on HIV progression of single nucleotide
      polymorphisms in promoters of the genes for tumour necrosis factor (TNF)-alpha
      and interleukin (IL)-10 and known to influence cytokine production. METHODS:
      Survival was documented for 4.3 years after baseline for 198 HIV-1-infected and
      180 HIV-uninfected individuals from the Mupfure Schistosomiasis and HIV Cohort in
      rural Zimbabwe. Polymorphisms determined were -592C>A and -1082A>G for IL-10 and 
      238G>A and -308G>A for TNF-alpha. CD4 cell counts, plasma HIV RNA, soluble TNF
      receptor II (sTNF-rII), IL-8 and IL-10 were also measured. RESULTS: Mortality was
      lower in carriers of the IL-10 -1082G high-producer allele (hazard ratio, 0.47; P
      < 0.01). CD4 cell count decrease in participants reporting for the follow-up at 3
      years was attenuated in carriers of this allele (P < 0.01). In univariate
      analysis, plasma IL-10, IL-8, and sTNF-rII correlated negatively with CD4 cell
      count, positively with HIV RNA, and higher levels predicted mortality. In
      multivariate analysis only sTNF-rII was an independent predictor of HIV
      progression markers and mortality. Indeed, sTNF-rII predicted mortality (P <
      0.01) at a level of significance comparable to HIV RNA (P < 0.01) and CD4 cell
      count (P < 0.05). CONCLUSIONS: In carriers of IL-10 -1082G, an allele linked to
      increased IL-10 production, survival was doubled and CD4 cell decrease was
      attenuated compared with noncarriers. Only sTNF-rII and not plasma IL-10 was an
      independent predictor of HIV progression markers and mortality. This study
      supports immune activation as a driving force in HIV pathogenesis and indicates a
      protective role of IL-10 -1082G that should be evaluated in other cohorts.

PMID- 18090277
TI  - Positive outcomes of HAART at 24 months in HIV-infected patients in Cambodia.
AB  - OBJECTIVES: African and Asian cohort studies have demonstrated the feasibility
      and efficacy of HAART in resource-poor settings. The long-term virological
      outcome and clinico-immunological criteria of success remain important questions.
      We report the outcomes at 24 months of antiretroviral therapy (ART) in patients
      treated in a Medecins Sans Frontieres/Ministry of Health programme in Cambodia.
      METHODS: Adults who started HAART 24 +/- 2 months ago were included. Plasma HIV
      RNA levels were assessed by real-time polymerase chain reaction. Factors
      associated with virological failure were analysed using logistic regression.
      RESULTS: Of 416 patients, 59.2% were men; the median age was 33.6 years. At
      baseline, 95.2% were ART naive, 48.9% were at WHO stage IV, and 41.6% had a body
      mass index less than 18 kg/m. The median CD4 cell count was 11 cells/microl. A
      stavudine-lamivudine-efavirenz-containing regimen was initiated predominantly
      (81.0%). At follow-up (median 23.8 months), 350 (84.1%) were still on HAART, 53
      (12.7%) had died, six (1.4%) were transferred, and seven (1.7%) were lost to
      follow-up. Estimates of survival were 85.5% at 24 months. Of 346 tested patients,
      259 (74.1%) had CD4 cell counts greater than 200 cells/microl and 306 (88.4%) had
      viral loads of less than 400 copies/ml. Factors associated with virological
      failure at 24 months were non-antiretroviral naive, an insufficient CD4 cell gain
      of less than 350 cells/microl or a low trough plasma ART concentration. In an
      intention-to-treat analysis, 73.6% of patients were successfully treated.
      CONCLUSION: Positive results after 2 years of advanced HIV further demonstrate
      the efficacy of HAART in the medium term in resource-limited settings.

PMID- 18090278
TI  - Frequent detection of acute HIV infection in pregnant women.
AB  - BACKGROUND: Universal prenatal HIV antibody testing, which does not detect acute
      HIV, is standard for pregnant women in the United States. Unrecognized HIV
      acquisition during pregnancy may result in higher rates of perinatal
      transmission. OBJECTIVE: To determine the prevalence of acute (antibody-negative)
      HIV infection in pregnant women and to assess the potential for prompt initiation
      of antiretroviral therapy to prevent perinatal transmission. METHODS: From 1
      November 2002 to 30 April 2005, all publicly funded HIV testing sites
      participated in North Carolina's Screening and Tracing Active Transmission (STAT)
      Program, which retested all specimens that were HIV antibody negative for HIV RNA
      using specimen pooling. All patients with acute HIV infection were immediately
      traced for evaluation, confirmatory testing, counseling, and referral services.
      For this study, all pregnant women with acute HIV were immediately initiated onto
      antiretroviral therapy and followed prospectively for pregnancy outcomes.
      RESULTS: During the study period, 443 women were HIV positive by antibody
      testing; 15 were HIV antibody negative but positive by RNA assay and of these
      five were pregnant at the time of testing. The pregnant women received
      antiretroviral drugs and delivered HIV-uninfected infants. Maternal testing
      records of all six HIV-infected infants born in North Carolina showed three
      mothers with chronic HIV infection and three HIV antibody negative at private
      prenatal testing facilities. CONCLUSIONS: In resource-rich settings, a
      substantial proportion of residual perinatal transmission may be from HIV
      acquisition during pregnancy. Standard antibody tests miss acute HIV infection
      and so algorithms that include pooled HIV RNA testing may improve its detection
      and represent a further opportunity to prevent perinatal transmission.

PMID- 18090279
TI  - Serological testing algorithm shows rising HIV incidence in a UK cohort of men
      who have sex with men: 10 years application.
AB  - OBJECTIVES: To investigate whether combining clinical data with the serological
      testing algorithm for recent HIV seroconversion (STARHS) reliably identifies
      otherwise unrecognized recent infections and observe their trends. DESIGN:
      Incorporation of STARHS into routine HIV diagnosis. METHODS: STARHS was applied
      to serum collected between 1996 and 2005 at HIV diagnosis and routine
      clinical/laboratory markers of recent infections were determined. The recent
      infections were identified by conventional means, by STARHS, and by both
      combined. RESULTS: Of 1526 infections diagnosed, 812 were new. Of these, 604 were
      in men who have sex with men (MSM); 208 in heterosexuals; 88% had serum available
      for STARHS, which identified 88 incident infections that would otherwise have
      been unrecognized (12% of all new infections, 34% of all recent infections). Of
      these, 88% reported recent high-risk sex; 47% reported seroconversion symptoms.
      STARHS confirmed recent infections in 71 of 74 (96%) known to be infected within
      6 months by conventional methods. Combining both approaches, recent infections
      increased over time from 26% (1996) to 45% (2005) [P < 0.001]. STARHS results
      from 3% new diagnoses and 8% previous diagnoses were deemed false incident
      (associated with antiretroviral therapy, advanced disease or undetectable viral
      load). False incident results were only inexplicable in two individuals.
      CONCLUSION: Adjunctive use of STARHS with clinical data identified a high and
      increasing proportion of new HIV diagnoses as recent infections, confirming
      significant ongoing transmission. Since 2002, 50% of new diagnoses among MSM were
      recent infections. Identification of additional recent infections by STARHS
      enables effective intervention that may benefit the individual and reduce onward
      transmission.

PMID- 18090280
TI  - Antiretroviral therapy with the integrase inhibitor raltegravir alters decay
      kinetics of HIV, significantly reducing the second phase.
AB  - OBJECTIVE: Raltegravir (MK-0518) belongs to the new class of HIV integrase
      inhibitors. To date, there have been no reports investigating the potential for
      differential effects on viral dynamics with integrase inhibitors relative to
      current antiretroviral drugs. METHODS: Patients in this phase II study (P004)
      were antiretroviral treatment naive. Part 1 of this study compared monotherapy
      with raltegravir (100 mg, 200 mg, 400 mg, or 600 mg twice daily) with placebo
      over 10 days. In part 2, patients were enrolled for 48 weeks of combination
      therapy, with randomization to one of the four dosages of raltegravir or to
      efavirenz, in addition to tenofovir and lamivudine. Mathematical models were used
      to investigate processes underlying viral dynamics. RESULTS: From day 15 through
      to day 57, individuals in the raltegravir arm were significantly more likely to
      have HIV RNA < 50 copies/ml (P < or = 0.047). Plasma viral loads were 70% lower
      at initiation of second-phase decay for individuals taking raltegravir than for
      those taking efavirenz (P < 0.0001). This challenges the current hypothesis that
      second-phase virus originates from infected long-lived cells, as an integrase
      inhibitor should not impact on viral production from this cell population.
      Mathematical modeling supported two hypotheses as consistent with these
      observations: (i) that second-phase virus arises from cells newly infected by
      long-lived infected cells and (2) that it arises from activation of latently
      infected cells with full-length unintegrated HIV DNA. CONCLUSIONS: These
      observations challenge the current understanding of HIV-1 turnover and
      compartmentalization. They also indicate the promise of this new integrase
      inhibitor raltegravir.

PMID- 18090281
TI  - Sexual network structure and the spread of HIV in Africa: evidence from Likoma
      Island, Malawi.
AB  - BACKGROUND: Whereas sexual relationships among low-risk individuals account for
      the majority of HIV infections in sub-Saharan Africa, limited knowledge exists
      about the structure and characteristics of sexual networks among the general
      population in sub-Saharan Africa. OBJECTIVES: To investigate the population-level
      structure of sexual networks connecting the young adult population of several
      villages on Likoma Island (Malawi), and analyse the structural position of HIV
      positive individuals within the sexual network. DESIGN AND METHODS: A cross
      sectional sociocentric survey of sexual partnerships and biomarkers of prevalent
      HIV infections. RESULTS: The study documents the existence of a large and robust
      sexual network linking a substantial fraction of the island's young adult
      population: half of all sexually active respondents were connected in a giant
      network component, and more than a quarter were linked through multiple
      independent chains of sexual relationships. This high network connectivity
      emerges within short time frames. The prevalence of HIV also varied significantly
      across the network, with sparser regions having a higher HIV prevalence than
      densely connected components. Several risk factors related to sexual mixing
      patterns help explain differentials in HIV prevalence across network locations.
      CONCLUSION: Contrary to claims that sexual networks in rural sub-Saharan Africa
      are too sparse to sustain generalized HIV epidemics, the structure of the
      networks observed in Likoma appears compatible with a broad diffusion of HIV
      among lower-risk groups. The non-homogeneous distribution of HIV infection within
      the network suggests that network characteristics are an important determinant of
      the dynamics of HIV spread within a population.

PMID- 18090282
TI  - HIV seroprevalence in street youth, St. Petersburg, Russia.
AB  - BACKGROUND: Reliable data on HIV infection among Russian street youth are
      unavailable. The purpose of this study was to assess HIV seroprevalence among
      street youth in St Petersburg and to describe social, sexual, and behavioral
      characteristics associated with HIV infection. METHODS: A cross-sectional
      assessment conducted during January-May 2006 included city-wide mapping of 41
      street youth locations, random selection of 22 sites, rapid HIV testing for all
      consenting 15-19-year-old male and female street youth at these sites, and an
      interviewer-administered survey. Adjusted odds ratios (AOR) were calculated using
      logistic regression, accounting for intracluster homogeneity. RESULTS: Of 313
      participants, 117 (37.4%, 95% confidence interval 26.1-50.2%) were HIV infected.
      Subgroups with the highest seroprevalences included double orphans (64.3%), those
      with no place to live (68.1%), those previously diagnosed with a sexually
      transmitted infection (STI; 70.5%), those currently sharing needles (86.4%), and
      those currently using inhalants (60.5%) or injection drugs (78.6%), including
      Stadol (82.3%) or heroin (78.1%). Characteristics independently associated with
      HIV infection included injecting drugs (AOR 23.0), sharing needles (AOR 13.3),
      being a double or single orphan (AOR 3.3 and 1.8), having no place to live (AOR
      2.4), and being diagnosed with a STI (AOR 2.1). Most HIV-infected street youth
      were sexually active (96.6%), had multiple partners (65.0%), and used condoms
      inconsistently (80.3%). DISCUSSION: Street youth aged 15-19 years in St
      Petersburg, Russia, have an extraordinarily high HIV seroprevalence. In street
      youth who are injection drug users, HIV seroprevalence is the highest ever
      reported for eastern Europe and is among the highest in the world.

PMID- 18090283
TI  - HIV drug resistance after the use of generic fixed-dose combination
      stavudine/lamivudine/nevirapine as standard first-line regimen.
AB  - Early failures to stavudine/lamivudine/nevirapine used as a generic fixed-dose
      combination in Mali showed resistance mutations in 50% of cases (mostly M184V and
      Y181C). No thymidine analogue mutations were seen, suggesting that most
      nucleoside reverse transcriptase inhibitors could be used in a second-line
      regimen. This highlights the importance of the accessibility of HIV-RNA assays
      for monitoring treated patients in resource-poor countries to detect early
      virological failure in order to preserve future therapeutic options.

PMID- 18090284
TI  - Long-term persistence of memory B cells specific for hepatitis B surface antigen
      in HIV-1-infected patients.
AB  - To investigate the maintenance of long-term memory B cells specific for hepatitis
      B surface antigen (HBsAg), purified blood B cells were polyclonally stimulated
      and cells secreting antibodies directed to HBsAg (HBs-SC) enumerated by ELISpot.
      HBs-SC were found in 18/20 HIV-1-infected patients with either natural or
      vaccinal immunity to hepatitis B virus, including six subjects with serum anti
      hepatitis B surface antibody levels less than 10 mIU/ml. A lower number of HBs-SC
      was found in HBsAg-vaccinated patients compared with vaccinated controls.

PMID- 18090285
TI  - High rate of extensively drug-resistant tuberculosis in Indian AIDS patients.
AB  - Fifty-four full-blown AIDS patients suspected of having HIV-tuberculosis co
      infection were investigated for the prevalence of extensively drug-resistant
      (XDR) Mycobacterium tuberculosis. Out of the 54 patients, M. tuberculosis was
      isolated from 24 (44.4%). Twelve (50%) isolates of these had resistance to first
      line drugs, whereas four (33.33%) were also resistant to second-line drugs. All
      four patients, in whom XDR M. tuberculosis was isolated, died within 2.6 months
      of diagnosis.

PMID- 18090286
TI  - Do CD8(+)CD25(+) cells predict immune reconstitution syndrome in HIV-positive
      patients who begin HAART?
AB  - Although undesirable, immune reconstitution syndrome (IRS) indicates a favourable
      effect of HAART and it should be differentiated from an opportunistic infection
      because of their distinct implications and management. Our group analysed
      different immunological parameters with the aim of identifying IRS predictors in
      patients who begin HAART. We found that CD8(+)CD25(+) cell pretreatment values in
      patients who developed IRS were four times higher than in those patients who did
      not develop IRS.

PMID- 18090287
TI  - Same race and older partner selection may explain higher HIV prevalence among
      black men who have sex with men.
AB  - In a community-based survey in San Francisco, black men who have sex with men
      (MSM) had higher rates of same-race/ethnicity sexual partnerships and partners 10
      or more years older compared with other MSM. Differences in sexual networks may
      explain why black MSM have higher HIV prevalence than other MSM despite lower
      levels of risk behavior.

PMID- 18090288
TI  - Prevalence of HIV-2 and HIV-1 group O infections among new HIV diagnoses in
      France: 2003-2006.
AB  - French national surveillance of new HIV diagnoses included the collection of
      dried serum spots to identify HIV serotypes. Between January 2003 and June 2006,
      10,184 new diagnoses were reported. The proportions of HIV-2 and HIV-1 group O
      infections were 1.8 and 0.1%, respectively. Most of these cases occurred in
      patients infected through heterosexual contact and originated from the
      corresponding endemic areas. Three cases of HIV-2 infections were reported in non
      African men having sex with men.

PMID- 18090289
TI  - Primary penile angiosarcoma in a patient with AIDS: a case report.

PMID- 18090290
TI  - Response to Brown et al., 'Incident and prevalent herpes simplex virus type 2
      infection increases risk of HIV acquisition among women in Uganda and Zimbabwe'.

PMID- 18090291
TI  - Atazanavir crystal nephropathy.

PMID- 18090292
TI  - Geographical biases and convenience sampling in HIV molecular epidemiology
      estimates.

PMID- 18090293
TI  - Resistance mutation patterns in plasma and breast milk of HIV-infected women
      receiving highly-active antiretroviral therapy for mother-to-child transmission
      prevention.

PMID- 18090294
TI  - Hepatic involvement with tuberculosis-associated immune reconstitution disease.

PMID- 18090295
TI  - Dysfunctional natural killer cells, in vivo, are governed by HIV viremia
      regardless of whether the infected individual is on antiretroviral therapy.

PMID- 18090296
TI  - Entecavir can select for M184V of HIV-1: a case of an HIV/hepatitis B (HBV) naive
      patient treated for chronic HBV.

PMID- 18090297
TI  - Effects of atazanavir/ritonavir and lopinavir/ritonavir on glucose uptake and
      insulin sensitivity.

PMID- 18090299
TI  - Higher-than-expected rates of lactic acidosis among highly active antiretroviral
      therapy-treated women in Botswana: preliminary results from a large randomized
      clinical trial.
AB  - BACKGROUND: The ability of nucleoside reverse transcriptase inhibitors (NRTIs) to
      inhibit human mitochondrial polymerase-gamma results in impaired synthesis of
      mitochondrial enzymes that generate adenosine triphosphate (ATP) by oxidative
      phosphorylation. This has been associated with several long-term mitochondrial
      toxicities, which include lactic acidosis and pancreatitis, peripheral
      neuropathy, and lipoatrophy. METHODS: Enrolled highly active antiretroviral
      therapy (HAART)-treated adults have completed nearly 2 years of follow-up as part
      of the ongoing randomized clinical trial Adult Antiretroviral Treatment and Drug
      Resistance (Tshepo) study. All patients were intensively screened for the
      presence of ARV-related toxicities. RESULTS: Six hundred fifty adults (69%
      female) were initiated on NRTI-based HAART. Overall, 2.0% of patients developed
      moderate to severe symptomatic hyperlactatemia, with 7 (1.0%), all female,
      diagnosed with lactic acidosis. Female gender (P = 0.008) and being overweight,
      namely having a body mass index (BMI) of greater than 25 (P = 0.001), were
      predictive for the development of moderate to severe symptomatic hyperlactatemia
      or lactic acidosis. Older age (age >40 years) showed a statistical trend (P =
      0.053) as a predictor for the development of toxicity, whereas exposure to d4T
      and/or ddI for 6 or more months was not predictive (P = 0.102). Those diagnosed
      with lactic acidosis had a mean BMI of 32.38 (interquartile range [IQR] = 29.4 to
      35) at the time of toxicity and had been receiving HAART for a mean of 12.1
      months (IQR = 7 to 20.8). Four of the 7 (57%) died of lactic acidosis and/or
      hemorrhagic pancreatitis; these 4 patients also had a comorbid diagnosis of
      severe clinical pancreatitis with grade 3/4 lipase elevations and abdominal
      symptoms at the time of their demise. CONCLUSIONS: Rates of lactic acidosis
      appear to be higher in southern Africa when compared with rates previously
      described elsewhere. Risk factors for the development of moderate to severe
      symptomatic hyperlactatemia or lactic acidosis appear to be multifactorial but
      include female gender and having a BMI of greater than 25. Additional studies are
      ongoing to evaluate for other possible risk factors, such as host genetic
      differences.

PMID- 18090300
TI  - Effects of cotrimoxazole on hematologic parameters in HIV-infected adults in a
      community-based clinic in Entebbe, Uganda.

PMID- 18090301
TI  - The role of early viral decline in the treatment of hepatitis C in HIV-1
      coinfected persons.

PMID- 18090302
TI  - Determinants of HIV-1 genotypic resistance to darunavir (TMC114) in a large
      Italian resistance database (Antiretroviral Resistance Cohort Analysis).

PMID- 18090303
TI  - Immune activation and increased prevalence of thrombosis in HIV infection.

PMID- 18090304
TI  - Rapid HIV testing on labor and delivery: lessons from the field.

PMID- 18090305
TI  - Knowledge and use of preexposure and postexposure prophylaxis among attendees of
      Minority Gay Pride events, 2005 through 2006.

PMID- 18090306
TI  - Reorganization of neural circuits in the blind on diffusion direction analysis.
AB  - The neural reorganization of the visual cortex of early blind individuals was
      evaluated using voxel-by-voxel analysis of diffusion tensor images with regard to
      the diffusion direction, diffusion anisotropy and diffusivity. Reduced anisotropy
      and increased diffusivity was found mainly in the visual pathways of 18 early
      blind individuals as opposed to 25 sighted individuals. Alteration of the
      diffusion direction was detected not only in the visual pathways but also in
      nonvisual pathways such as the u fibers of the parietal lobe, the sagittal
      striatum, the pulvinar and the inferior and superior longitudinal fasciculi. The
      alteration of regional diffusion direction, reduced anisotropy and increased
      diffusivity in early blind individuals imply the neural reorganization for
      functional adaptation to the loss of visual input during the early development
      period.

PMID- 18090307
TI  - Association between SORL1 and Alzheimer's disease in a genome-wide study.
AB  - Several studies have reported an association of Alzheimer's disease (AD) with
      polymorphic markers in SORL1. Data from a recently published genome-wide
      association study in AD have been made publicly available. We tested the
      association of AD with SORL1 in this dataset (Translational Genomics Research
      Institute; TGEN), which included 31 SORL1 single nucleotide polymorphisms (SNPs),
      eight of which overlapped the original study. Six SNPs, near the 3' region of
      SORL1 containing SNPs which were strongly associated with AD in previous studies,
      showed significant association in the TGEN dataset. These results provide an
      independent replication of the association between AD and SORL1.

PMID- 18090308
TI  - Sensilla position on antennae influences afferent terminal location in glomeruli.
AB  - The spatial distribution of chemosensory afferent terminals within glomeruli,
      with respect to their peripheral origin, was investigated using differential
      staining of afferents in the cockroach. In all glomeruli, the axon terminals of
      afferents originating from the more distal regions of the flagellum tended to
      occur in the more distal regions of the glomeruli, relative to the axonal entry
      side. Afferent terminals tend to be spatially separated, on the basis of their
      circumferential origin on the flagellum, in pheromone-receptive glomerular
      complexes and posterodorsally located large glomeruli; however, they were
      randomly scattered in anteroventrally located small glomeruli. These results
      revealed that the location of afferent terminals strongly reflects the three
      dimensional position of their olfactory receptor neurons in pheromone-receptive
      glomeruli, but the relationship is weaker in other glomeruli.

PMID- 18090309
TI  - Remembering the good times: neural correlates of affect regulation.
AB  - The ability to regulate one's mood state effectively is critical to emotional and
      physical health. Recent investigations have sought to delineate the neural
      mechanisms by which individuals regulate mood states and emotions, positing a
      critical role of a dorsal system that includes the dorsolateral prefrontal cortex
      and anterior cingulate. This study extended these efforts by examining the neural
      correlates of retrieving positive autobiographical memories while experiencing a
      negative mood state in a sample of healthy female adults. We demonstrated that
      mood-incongruent recall is associated with activation in ventrolateral and
      ventromedial prefrontal cortices (including orbitofrontal cortex and subgenual
      cingulate). These findings suggest that mood-incongruent recall differs from
      other affect regulation strategies by influencing mood through a ventral
      regulatory network.

PMID- 18090310
TI  - Phonological influences on lexicosemantic processing of kanji words.
AB  - To investigate the phonological influences on the lexicosemantic process with a
      strong orthographic constraint, we used kanji (morphogram) homophone words and
      measured, using magnetoencephalography, the neural activities during the silent
      reading of prime-target pairs. The primes were phonologically the same as or
      different from the targets or pseudocharacters. The neural activities in the left
      posterior temporal and inferior parietal areas became weaker with phonological
      repetition. Furthermore, stronger activities for the different condition in the
      left anterior temporal area and for the same condition in the left inferior
      frontal cortex, respectively, suggest the roles of these areas of the brain in
      the semantic processing of words and in the selection of appropriate meanings. We
      conclude that phonological information affects the lexicosemantic process even
      with a strong orthographic constraint.

PMID- 18090311
TI  - Ablation of p27 enhance kainate-induced seizure and hippocampal degeneration.
AB  - p27 is a cyclin-dependent kinase inhibitor which arrests cell cycle at G1-S
      phase. Using RNA interference method, we previously showed that reduction of
      endogenous p27 expression induces cell death through cell cycle progression in
      cultured cortical neurons. In this study, we investigated responses to kainate
      treatment using p27 knockout mice. Injection of kainic acid induced p27
      downregulation and retinoblastoma protein phosphorylation in wild-type mouse
      hippocampus. No change was observed in hippocampal cell viability in untreated
      adult p27 heterozygous and homozygous mice compared with wild type (+/+). p27
      homozygous mice, however, displayed enhanced seizure and hippocampal degeneration
      after kainic acid treatment. This study first suggests that ablation of p27
      enhance kainate-induced seizure and hippocampal cell death in vivo.

PMID- 18090312
TI  - Shape deformation of the insula in alcoholics: reduction of left-right asymmetry.
AB  - We have investigated shape deformation of the insula to get a viewpoint of how
      chronic alcohol consumption affects the perisylvian region and compared the
      deformity pattern between the left and right hemisphere. A landmark-based
      structural and surface shape analysis of the insula was performed in 20 patients
      with alcohol dependence and 20 controls matched for age. The shape analysis
      revealed that the left and right insula follow distinct shape deformation
      patterns, which resulted in the reduction of left-right asymmetry. The shape
      deformity was most prominent in the central part of both insula. Our findings
      indicate that the right and left hemisphere are both affected but shows distinct
      patterns of deformation in alcohol dependence.

PMID- 18090313
TI  - Auditory scene analysis following unilateral inferior colliculus infarct.
AB  - Event-related potentials in the form of mismatch negativity were recorded to
      investigate auditory scene analysis capabilities in a person with a very
      circumscribed haemorrhagic lesion at the level of the right inferior colliculus.
      The results provide the first objective evidence that processing at the level of
      the inferior colliculus plays an important role in human auditory frequency
      discrimination. Moreover, the electrophysiological data suggest that following
      this unilateral lesion, the auditory pathways fail to reorganize efficiently.

PMID- 18090314
TI  - Lateralized parietal activity during decision and preparation of saccades.
AB  - The posterior parietal cortex is involved in numerous visuospatial tasks, but
      little is known about the lateralization of these functions. We used functional
      magnetic resonance imaging to map the posterior parietal areas involved in
      saccades. Cerebral activation was studied during three different steps of
      saccadic elaboration: internal Decision of where to direct a horizontal saccade,
      motor Preparation and saccade Execution. These steps activated distinct areas:
      Decision and Preparation selectively activated the left posterior parietal cortex
      (left deep posterior intraparietal sulcus and left medial posterior intraparietal
      sulcus), whereas Execution activated only the right posterior parietal cortex
      (right medial posterior intraparietal sulcus). In humans, left but not right
      posterior parietal cortex might be specifically related to decision making and
      preparation of forthcoming ocular saccades.

PMID- 18090315
TI  - Decreased proliferation of hippocampal progenitor cells in APPswe/PS1dE9
      transgenic mice.
AB  - A recent hypothesis suggests that there is impaired hippocampal neurogenesis in
      Alzheimer's disease. Here we examined the proliferation, the first stage in
      neurogenesis, of hippocampal progenitor cells in amyloid precursor protein with
      Swedish mutation and presenilin-1 with deletion of exon 9 (APPswe/PS1dE9)
      transgenic mice. Compared with age-matched wild-type mice, transgenic mice at 5
      months of age with low amyloid beta-peptide (Abeta) levels and subtle Abeta
      deposits showed normal proliferation of hippocampal progenitor cells; however,
      transgenic mice at 9 months of age with high Abeta levels and numerous Abeta
      deposits showed decreased proliferation of these cells. The number of
      proliferating cells in male transgenic mice was indistinguishable from that in
      female transgenic mice. These results indicate that neurogenesis is decreased
      with degrees of Abeta pathology, and that there is no gender difference in their
      proliferation in APPswe/PS1dE9 transgenic mice.

PMID- 18090316
TI  - How 'special' is the human face? Evidence from an audiovisual temporal order
      judgment task.
AB  - Upright and inverted audiovisual video clips of a monkey producing a 'coo' and a
      human imitating this vocalization were presented at a range of stimulus onset
      asynchronies. Participants made temporal order judgments regarding which modality
      stream appeared to have been presented first. The results showed that inverting
      the dynamic human visual display led to a significant differences in the point of
      subjective simultaneity, with the inverted human faces requiring more time to be
      processed compared with the upright displays. No such inversion effect was found
      for the monkey visual displays. These results demonstrate that the effect of
      inversion on the temporal perception of audiovisual speech stimuli are driven by
      the viewing of a human face rather than by the integration of audiovisual speech.

PMID- 18090317
TI  - Rotenone enhances N-methyl-D-aspartate currents by activating a tyrosine kinase
      in rat dopamine neurons.
AB  - Our previous work showed that the pesticide rotenone increases the amplitude of
      inward currents evoked by N-methyl-D-aspartate (NMDA) in substantia nigra
      dopamine neurons. Using patch pipettes to record whole-cell currents in rat brain
      slices, we report that the rotenone-induced potentiation of NMDA current is
      blocked by the tyrosine kinase inhibitors genistein and PP1. This action of
      rotenone is mimicked by H2O2, which is also blocked by genistein. Our results
      suggest that the rotenone-dependent increase in NMDA current is mediated by
      release of reactive oxygen species that activates a protein tyrosine kinase.

PMID- 18090318
TI  - Neuromuscular block and the electroencephalogram during sevoflurane anaesthesia.
AB  - The effect of neuromuscular block on the anaesthetic depth of hypnosis is an
      elusive question. We simultaneously investigated the influence of neuromuscular
      block on the bispectral index, a measure of hypnosis during general anaesthesia,
      and on the electroencephalogram. Patients were anaesthetized with sevoflurane.
      Noxious tetanic electrical stimulation was applied on two occasions: before and
      after profound neuromuscular block achieved with rocuronium. Neuromuscular block
      significantly attenuated the effect from noxious stimulation on
      electroencephalogram power and synchrony in the gamma band (P<0.05), and the
      corresponding effect on bispectral index (P<0.02). These findings are probably
      due to the reduced arousing afferent input from paralysed muscles, and not to
      changes in the frontal electromyogram.

PMID- 18090319
TI  - The tropism of embryoid body cells for glioma cells.
AB  - It has been demonstrated that several types of adult stem cells have a common
      attribute of tropism for gliomas. In our study, we provided evidence that
      embryonic stem cell-derived embryoid body (EB) cells also exhibited a tropism for
      gliomas. Chemotaxis assays and organotypic hippocampal slice culture experiments
      showed that EB cells were attracted by the conditioned medium from C6 glioma
      cells and by C6 glioma cells deposited on the slice. Aggregate culture assays
      showed that EB cells could coaggregate with C6 glioma cells. Embryoid body cells
      injected intratumorally were found to distribute throughout the tumor mass. All
      data indicated that EB cells displayed a tropism for gliomas.

PMID- 18090320
TI  - Hypoxia suppresses kainate-induced gamma-oscillations in rat hippocampal slices.
AB  - Hypoxia or global ischemia causes rapid loss of consciousness and a sudden
      increase in spontaneous transmitter release suggesting that coordinated synaptic
      activity is impaired. Gamma oscillations (30-100 Hz) are thought to provide for
      binding of parallel processed information in the brain, contributing to cognition
      and formation of short-term memory. We hypothesized that gamma-oscillations are
      rapidly blocked by hypoxia and that prolonged hypoxia reduces the capability to
      generate such activity. In ventral hippocampal slices, kainate-induced gamma
      oscillations reversibly declined 40 s after onset of 3 min hypoxia. Repetition of
      such hypoxic periods led to accumulative impairment of gamma-activities. By
      contrast, 6 min of hypoxia led to a transient anoxic depolarization after which
      gamma-oscillations remained almost completely blocked.

PMID- 18090321
TI  - Dopamine signaling and the distal reward problem.
AB  - Actions and their associated consequences, such as reward attainment, are often
      temporally distant. Animals nevertheless learn such associations thereby solving
      the 'distal reward' problem. We sought to determine whether dopamine signaling
      plays a role in such learning. Wild-type and dopamine type I receptor knockout
      mice executed three left/right choices leading to one of eight differentially
      rewarded goal sites. Compared with wild-type mice, knockouts exhibited selective
      impairments in decision making at choice points distal, but not proximal, to goal
      sites. We conclude that dopamine's role in reinforcement learning depends on the
      temporal relationship of actions to reward and that dopamine signaling through D1
      receptors constitutes a component of those brain mechanisms responsible for
      solving the distal reward problem.

PMID- 18090322
TI  - Does repetition engender the same retrieval processes in young and older adults?
AB  - Aging differentially affects retrieval processes underlying recognition memory:
      familiarity is maintained, whereas recollection declines. We determined whether
      word repetition across two study-test phases enhanced older adults' use of
      recollection. During Test 1, frontal episodic memory effects, suggestive of
      familiarity-based processes, were age invariant, whereas only the young showed a
      parietal episodic memory effect, suggestive of recollection. Repetition did not
      modulate the frontal episodic memory effect in either group, but increased the
      parietal episodic memory effect in the young. Importantly, older adults showed a
      parietal episodic memory effect at Test 2, suggesting that repetition did enable
      recollection. Only older adults, however, showed a left frontal negativity,
      implying that they may have used additional processes to recover episodic
      memories.

PMID- 18090323
TI  - Expression of phosphodiesterase 4 is altered in the brains of subjects with
      autism.
AB  - The cyclic adenosine monophosphate-specific phosphodiesterase-4 (PDE4) gene
      family is the target of several potential therapeutic inhibitors and the PDE4B
      gene has been associated with schizophrenia and depression. Little, however, is
      known of any connection between this gene family and autism, with limited
      effective treatment being available for autism. We measured the expression of
      PDE4A and PDE4B by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      Western blotting in Brodmann's area 40 (BA40, parietal cortex), BA9 (superior
      frontal cortex), and cerebellum from subjects with autism and matched controls.
      We observed a lower expression of PDE4A5, PDE4B1, PDE4B3, PDE4B4, and PDE4B2 in
      the cerebella of subjects with autism when compared with matched controls. In
      BA9, we observed the opposite: a higher expression of PDE4AX, PDE4A1, and PDE4B2
      in subjects with autism. No changes were observed in BA40. Our results
      demonstrate altered expressions of the PDE4A and PDE4B proteins in the brains of
      subjects with autism and might provide new therapeutic avenues for the treatment
      of this debilitating disorder.

PMID- 18090324
TI  - White matter integrity of the whole brain is disrupted in first-episode remitted
      geriatric depression.
AB  - Previous studies have demonstrated lower-diffusion anisotropy within white matter
      in late-onset depression measured by diffusion tensor imaging, which provides
      information about brain white matter integrity. We have examined whether white
      matter is abnormal in first-episode remitted geriatric depression by using
      diffusion tensor imaging. Sixteen remitted geriatric depression patients and 14
      well matched healthy controls underwent diffusion tensor-imaging scans of
      magnetic resonance imaging, which were analyzed by a rigorous voxel-based
      approach. We found that fractional anisotropy in white matter was lower in
      patients than in controls at the right superior frontal gyrus, left inferior
      frontal gyrus, left middle temporal gyrus, right inferior parietal lobule, right
      middle occipital gyrus, left lingual gyrus, right putamen and right caudate.
      These results suggested that the white matter integrity of the whole brain was
      disrupted in first-episode remitted geriatric depression, and that these
      abnormalities were perhaps involved in the psychopathology and pathophysiology of
      cognitive impairment in remitted geriatric depression.

PMID- 18090325
TI  - The P600 reflects cost of new information in discourse memory.
AB  - Discourse processing depends on long-term semantic memory and discourse memory
      (i.e. the organization and maintenance of a mental model). Using event-related
      potentials, the information-processing functions of the activities manifested by
      a centroparietal negativity (N400) and a posterior positivity (P600) were
      investigated during the processing of inferences. On the basis of findings from
      semantic priming, it was predicted that the standard N400 signature would
      modulate differences in the degree of inferential processing (semantic memory).
      Instead of N400 modulations, however, the two conditions that depended on a more
      demanding drawing of inferences elicited a P600, indicating that updating the
      mental model encumbers discourse memory capacity. The results highlight the
      functional significance of this positivity for discourse updating, and support
      the view that the P600 reflects distinct language processes.

PMID- 18090326
TI  - In-vitro and in-vivo antagonistic action of an anti-amylin Spiegelmer.
AB  - The anorectic and dipsogenic effects of the pancreatic hormone amylin are
      mediated by the area postrema and the subfornical organ. We tested the
      effectiveness of a new amylin antagonist, a so-called RNA Spiegelmer, by
      electrophysiological in-vitro recordings from the rat subfornical organ and by
      immunohistological c-Fos studies in the area postrema. Amylin's excitatory effect
      on subfornical organ neurons was blocked by the anti-amylin Spiegelmer.
      Peripheral administration 5 h prior to amylin also suppressed the amylin-induced
      activation (c-Fos expression) in the area postrema. The biostable anti-amylin
      Spiegelmer may be therapeutically beneficial in conditions associated with high
      plasma amylin levels, such as cancer anorexia occurring during certain pancreatic
      tumors.

PMID- 18090327
TI  - The effect of visual reliability on auditory-visual integration: an event-related
      potential study.
AB  - To investigate the neural mechanisms of auditory-visual integration, we recorded
      event-related potentials during a word-identification task, in which the stimulus
      was presented in the auditory (A), visual (V), and in the auditory-visual (AV)
      modalities. The reliability of the visual information varied at the high
      reliability (VH) and low-reliability (VL) levels in both the V and AV
      presentations. The modulation of sensory integrations owing to the variation of
      cue reliability was revealed in the format of the double-difference waveform
      generated by subtracting the difference waveform AVL-(A+VL) from the difference
      waveform AVH-(A+VH). The results demonstrated (i) the early modulation of the
      activity in the auditory and visual cortex; (ii) subsequent spatial-temporal
      sequence of activities mostly occurred in multisensory areas; and (iii) the
      timing of final outputs of AV integration at around 370-410 ms poststimulus.

PMID- 18090328
TI  - Cardiac sympathetic denervation in bradykinesia-dominant Parkinson's disease.
AB  - Cardiac iodine-123-labeled-metaiodobenzylguanidine uptake is reduced in early
      stage Parkinson's disease, suggesting sympathetic nerve degeneration. The
      scintigraphic findings in patients with Parkinson's disease with different
      clinical features have, however, not been established. Iodine-123-labeled
      metaiodobenzylguanidine myocardial scintigraphy was performed in 143 patients
      with Parkinson's disease. The early and delayed heart to mediastinum ratios were
      analyzed according to the dominant motor deficit (tremor, bradykinesia, rigidity,
      and postural instability), age, sex, age at onset, disease duration, and Hoehn
      and Yahr stage. Both ratios correlated with bradykinesia, age at disease onset,
      and disease duration; but not with sex, Hoehn and Yahr stage, tremor, rigidity,
      and postural instability. Our results suggest a close link between myocardial
      sympathetic degeneration and bradykinesia, age at onset and disease duration.

PMID- 18090329
TI  - Asymmetry in the auditory brainstem response following experience of monaural
      amplification.
AB  - Hearing aids can induce perceptual changes in some elderly listeners and there is
      recent evidence that this might be associated with reorganization within the
      auditory system. We compared the click-evoked auditory brainstem response in
      adults with and without monaural hearing aid experience. In listeners with
      monaural hearing aid experience, the mean peak-to-peak amplitude between wave V
      and SN10 was approximately 100 nV larger in the ear with hearing aid experience
      and this difference was statistically significant (P<0.01). The response was
      symmetrical in adults with no hearing aid experience. This suggests that hearing
      aids can induce physiological changes at the level of the auditory brainstem in
      elderly monaural hearing aid users.

PMID- 18090330
TI  - Error-related negativities elicited by monetary loss and cues that predict loss.
AB  - Event-related potential studies have reported error-related negativity following
      both error commission and feedback indicating errors or monetary loss. The
      present study examined whether error-related negativities could be elicited by a
      predictive cue presented prior to both the decision and subsequent feedback in a
      gambling task. Participants were presented with a cue that indicated the
      probability of reward on the upcoming trial (0, 50, and 100%). Results showed a
      negative deflection in the event-related potential in response to loss cues
      compared with win cues; this waveform shared a similar latency and morphology
      with the traditional feedback error-related negativity.

PMID- 18090331
TI  - Top 10 tips for coping with short staffing.

PMID- 18090332
TI  - What you need to know about ports.

PMID- 18090333
TI  - Choosing the best stethoscope.
AB  - Go beyond the bells and whistles to learn how to select this important assessment
      tool.

PMID- 18090334
TI  - Patient education. How to take care of your feet when you have diabetes.

PMID- 18090337
TI  - Injectable soft-tissue augmentation: the present and the future.

PMID- 18090338
TI  - A brief overview and history of temporary fillers: evolution, advantages, and
      limitations.
AB  - Facial soft-tissue augmentation by injection has become increasingly popular as a
      minimally invasive option for patients seeking cosmetic facial enhancement.
      Surgical rejuvenation procedures of the face often relate to a less than
      comprehensive solution to many of the changes that occur with age. Indeed, the
      surgical "lift," while providing the opportunity for soft-tissue repositioning,
      often fails to provide volumetric restoration to the face that is lost with
      aging. Appreciating the necessity of replacing depleted soft tissue has allowed
      for a more comprehensive approach to total facial rejuvenation. Hundreds of
      filling agents are available worldwide, and the enormity of options has led to
      confusion about which agents work best, where, and why. The vast array of
      available soft-tissue filling agents can be distilled into two simple categories:
      nonpermanent and permanent. In this article, the authors mostly limit their
      discussion, consistent with the mission of this supplement, to the evolution of
      nonpermanent filling agents, providing a rationale for their emergence and their
      individual use.

PMID- 18090339
TI  - Injectable collagens: lost but not forgotten--a review of products, indications,
      and injection techniques.
AB  - Soft-tissue augmentation and three-dimensional volume replacement remain a
      cornerstone of facial rejuvenation. There has been an exponential increase in
      interest in dermal fillers. Science and technology have kept pace with this
      demand, and currently there is a wide range of options from which to choose. This
      is especially well illustrated by the recent introduction of an entirely new
      class of agents--the hyaluronans. The temporary fillers (the collagens and the
      Zyderm and CosmoDerm families), however, remain an excellent alternative, as they
      have a well-documented safety record, there are multiple formulations that make
      them very versatile, and the admixture of local anesthetic decreases the
      discomfort of injection.

PMID- 18090340
TI  - Animal-based hyaluronic acid fillers: scientific and technical considerations.
AB  - BACKGROUND: Successful clinical application of dermal filler products requires an
      understanding of their physical characteristics and in vivo behavior. This study
      reviewed the data for hyaluronic acid dermal filler products derived from an
      animal source--the rooster comb. METHODS: A review of the hyaluronic acid
      literature was performed. Clinical experience with the animal-derived hyaluronic
      acid products was evaluated. RESULTS: The source of the hyaluronic acid has not
      been demonstrated to be a clinically important point of differentiation among
      filler products. Hypersensitivity reactions are rare and are also present in the
      products derived from bacteria. Variations that effect the hyaluronic acid
      products' physical characteristics and clinical performance are more closely
      related to cross-linking and formulation. Hyaluronic acid gel derived from animal
      sources is cross-linked by a sulfonyl-bis-ethyl bond and is a soft gel compared
      with other hyaluronic acid products. There is minimal gel swelling, which results
      in modest postinjection edema. Optimal clinical application favors patients who
      desire quick recovery and minimal palpability. CONCLUSIONS: Hyaluronic acid skin
      filler products derived from an animal source are safe and effective. Successful
      clinical application should be based on an understanding of the patient's goals
      and the choice of a hyaluronic acid product with the optimal characteristics.

PMID- 18090341
TI  - Non-animal-based hyaluronic acid fillers: scientific and technical
      considerations.
AB  - BACKGROUND: Recent advances in the technology and biocompatibility of the
      hyaluronans in all skin types mean that they are becoming the temporary facial
      filling agents of choice for many aesthetic physicians and surgeons. METHODS: The
      hyaluronan products that have been approved for clinical usage by the U.S. Food
      and Drug Administration and Health Canada were reviewed with respect to their
      composition, clinical effects and safety profiles, and potential complications.
      RESULTS: The currently approved accepted standard for the hyaluronan family of
      fillers of nonanimal bacterial origin includes Restylane and Perlane in the
      United States and Perlane, Restylane Touch, and SubQ in Canada. Also of nonanimal
      origin, Juvederm 24HV, 30, and 30HV were approved by the Food and Drug
      Administration in June of 2006. Another bacteria-derived hyaluronan filler is
      Captique; the Hylaform group of hyaluronan fillers is of animal origin and
      appears to be similar in effect and longevity to Captique. CONCLUSIONS: The
      remarkable biocompatibility of the hyaluronan group of agents in individuals of
      all skin types, allied with the superior aesthetic result and outstanding
      longevity of response, promises that patients will continue to demand safe these
      recent advances in filler technology.

PMID- 18090342
TI  - The role of hyaluronic acid fillers (Restylane) in facial cosmetic surgery:
      review and technical considerations.
AB  - BACKGROUND: Bioengineered hyaluronic acid derivatives are currently available
      that provide for safe and effective soft-tissue augmentation in the comprehensive
      approach to nonsurgical facial rejuvenation. Current hyaluronic acid fillers do
      not require preinjection skin testing and produce reproducible, longer-lasting,
      nonpermanent results compared with other fillers, such as collagen. METHODS: A
      review of the authors' extensive experience at the University of Texas
      Southwestern Medical Center was conducted to formulate the salient requirements
      for successful utilization of hyaluronic acid fillers. Indications, technical
      refinements, and key components for optimized product administration categorized
      by anatomical location are described. The efficacy and longevity of results are
      also discussed. RESULTS: Bioengineered hyaluronic acid fillers allow for safe and
      effective augmentation of selected anatomical regions of the face, when properly
      administered. Combined treatment with botulinum toxin type A can enhance the
      effects and longevity by as much as 50 percent. Key components to optimal filler
      administration include proper anatomical evaluation, changing or combining
      various fillers based on particle size, altering the depth of injection, using
      different injection techniques, and coadministration of botulinum toxin type A
      when indicated. Concomitant administration of hyaluronic acid fillers along with
      surgical methods of facial rejuvenation can serve as a powerful tool in
      maximizing a comprehensive treatment plan. CONCLUSIONS: Current techniques in
      nonsurgical facial rejuvenation and shaping with hyaluronic acid fillers are
      safe, effective, and long-lasting. Combination regimens that include surgical
      facial rejuvenation techniques and/or coadministration of botulinum toxin type A
      further optimize results, leading to greater patient satisfaction.

PMID- 18090343
TI  - Calcium hydroxylapatite (Radiesse) for correction of the mid- and lower face:
      consensus recommendations.
AB  - Restoring volume in the middle and lower portions of the face is becoming an
      indispensable component of modern facial rejuvenation. Radiesse (BioForm Medical,
      San Mateo, Calif.) is an injectable filler material composed of synthetic calcium
      hydroxylapatite microspheres (30 percent) suspended in an aqueous carrier gel (70
      percent). At present, Radiesse is indicated in the United States for correction
      of moderate to deep nasolabial folds and for correction of the signs of facial
      fat loss (lipoatrophy) in people with human immunodeficiency virus. Its off-label
      use in other facial aesthetic indications is widely reported in the literature.
      The ability of Radiesse to provide immediate and durable effects has fueled
      interest in its use for expanded aesthetic applications, particularly in the
      middle and lower face. The authors' consensus panel, consisting of a cross
      section of experts in plastic surgery, facial plastic surgery, and dermatology,
      was convened to review the scientific literature and compare clinical experiences
      regarding the use of calcium hydroxylapatite. This report describes the
      characteristic effects of aging in the middle and lower face and reviews the
      composition of calcium hydroxylapatite, its safety and durability, and its
      appropriate use in a variety of facial applications, including nasolabial folds,
      correction of human immunodeficiency virus-associated lipoatrophy, augmentation
      of the malar, submalar, and zygomatic regions, and correction of oral commissure
      defects, marionette lines, and prejowl sulcus. Recommendations for Radiesse use
      in each area, including anesthesia, and injection techniques are provided.
      Measures for enhancing patient comfort, anticipating and minimizing potential
      complications, and optimizing aesthetic results are also discussed.

PMID- 18090344
TI  - Practical use of Juvederm: early experience.
AB  - BACKGROUND: This article is intended to provide practical information on the use
      of Juvederm Ultra and Juvederm Ultra Plus injectable gel fillers and to highlight
      differences between the injection techniques and uses of these fillers and those
      of gel-particle suspensions. The author's purpose was to provide early
      information to clinicians who perform aesthetic surgery. METHODS: The author
      discusses the properties of the Juvederm family of products, compares these with
      particulate gel fillers, and makes recommendations for achieving optimal outcomes
      with Juvederm as well as dermal fillers in general. RESULTS: When correcting
      relatively fine and superficial lines, or for first-time treatment of the lips,
      Juvederm Ultra is preferred. Juvederm Ultra Plus is useful for correction of
      deeper wrinkles and folds. Cohesive, homogenous gel fillers such as Juvederm
      require gentle, gradual injection, which facilitates very accurate delivery to
      the site while minimizing the risk of disengagement of the needle from the Luer
      lock hub of the syringe. These fillers appear to remain in the desired location
      and do not flow away from the injection point into unintended areas, so that a
      somewhat smaller amount of filler is required for a given degree of correction.
      Both the Juvederm preparations tend to blend in with the treated area in a
      shorter period of time compared with gel-particle suspensions. Finally, cohesive
      gels appear to be associated with a lesser degree of swelling in the 24-hour
      period after the procedure, particularly in the lips. CONCLUSIONS: Juvederm Ultra
      and Juvederm Ultra Plus are new-generation hyaluronic acid fillers used to treat
      superficial lines and deeper folds, respectively. They require administration by
      gentle, gradual, and precise injection.

PMID- 18090345
TI  - Hyaluronic acid injections for correction of the tear trough deformity.
AB  - BACKGROUND: The tear trough, though small in physical dimensions, sits at the
      perceptual epicenter of the face. Because small changes here make large changes
      in how other people interpret one's state of being, it would be beneficial to
      have a simple way of addressing the area. Despite the complexities of cause, the
      solution is to level the hollow and smooth the junction between the lid and the
      cheek. METHODS: Hyaluronic acid injections are used to address the tear trough
      deformity. Very small quantities, 0.2 to 0.4 cc, are used per side, and the
      placement is in the orbicularis oculi muscle or at the periosteum. The key is to
      inject deep to the dermis and to massage the injected area smooth. RESULTS: All
      patients were improved roughly in proportion to their skin quality. The best
      patients for the treatment are those with young, thick skin and a definite
      hollow. The duration of the effect is often more than 1 year at this location.
      Minor bruising and irregularities were self-limiting or treated with light
      massage. Large overfills or irregularities are correctable with injection of
      hyaluronidase. CONCLUSIONS: Tear trough injection with hyaluronic acid products
      is relatively simple, effective, and safe, and can offer significant improvement
      in this difficult area. It can be performed for primary deformities or to improve
      a surgical result.

PMID- 18090346
TI  - Hyaluronic acid fillers and botulinum toxin type a: rationale for their
      individual and combined use for injectable facial rejuvenation.
AB  - Soft-tissue augmentation has seen a renaissance of interest, as an increasing
      number of patients seek aesthetic improvement without major downtime. Although
      injectable agents for soft-tissue augmentation have been widely available for
      more than 20 years, the renewed interest has been fueled in part by the
      introduction of botulinum toxin type A. The unequivocal establishment of
      predictable and aesthetic results, initially and primarily in the upper face,
      created a need for an agent that would work equally well in the lower face and
      that could be administered in an office setting. The marriage of these two
      injectables (hyaluronic acid and botulinum toxin type A) began with the
      escalating popularity of both of these substances individually and the
      realization that a more global aesthetic enhancement is provided by combining
      these agents in custom proportions to achieve maximum aesthetic effects. Although
      the authors discuss most of the related, available hyaluronic acid and botulinum
      toxin agents, their clinical experiences, and the scientific data regarding these
      products, they realize that the discussions have been weighted toward the
      products that have been available for use in the United States the longest. In
      this article, they attempt to explain some of the results of prior (to U.S. Food
      and Drug Administration approval) studies that have been the subject themselves
      of some confusion, and provide a rationale for using hyaluronic acids and
      botulinum toxin for facial enhancement independently and in combination.

PMID- 18090347
TI  - The role of autologous fat and alternative fillers in the aging face.
AB  - Soft-tissue fillers can be used successfully to restore volume loss caused by
      facial aging. Injectable fillers can be used in isolation or in conjunction with
      other facial rejuvenation procedures. To achieve a superior aesthetic result, the
      plastic surgeon must understand the key components of facial aging: soft-tissue
      atrophy, gravitational descent, and loss of skin tone. An accurate assessment of
      the relationship of these factors will determine the role of soft-tissue
      augmentation through the use of fillers. Because the majority of facial volume
      loss through aging is attributable to fat loss, the authors believe that
      autologous fat represents the ideal soft-tissue replacement. The authors describe
      the appropriate use of autologous fat and improvements in technique that have
      enhanced the predictability of facial fat grafting. When autologous fat is not an
      option, alternative facial fillers including calcium hydroxylapatite and
      hyaluronic acid may provide excellent results. The authors' algorithm for filler
      selection is based on relative morbidity, recipient-site characteristics, and the
      physical characteristics of each filler. This algorithm is discussed in the
      following anatomical regions: the nasolabial folds, glabellar crease, malar
      region, nasojugal groove, and lips. When used appropriately, soft-tissue fillers
      can contribute significantly to overall facial rejuvenation.

PMID- 18090348
TI  - Management of complications and sequelae with temporary injectable fillers.
AB  - BACKGROUND: Injectable nonpermanent soft-tissue augmentation materials are
      extremely well-tolerated products that can be used safely in virtually all
      patients who are candidates for facial augmentation. In this article, the authors
      review the management of the few common and minor undesirable effects that may be
      associated with temporary fillers; in addition, the authors mention the rare
      incidence of serious complications. METHODS: The authors conducted a MEDLINE
      based (1990 to 2005) review of complications and side effects of nonpermanent
      injectable filler materials. This review was supplemented with evidence presented
      at recent plastic surgery and dermatology scientific meetings and unpublished
      information made available to the authors. RESULTS: Nonpermanent injectable soft
      tissue augmentation materials are extremely safe substances that are unlikely to
      cause more than mild injection discomfort, transient redness and swelling, and
      occasional short-term bruising when used for facial augmentation. Symmetry can
      usually be maintained with judicious bilateral use of injectant, and injection
      site necrosis is rare and treatable. Proper technique minimizes the already very
      low risk of visible implants, nodule formation, and hypersensitivity reactions.
      Other serious effects are exceedingly rare, and retinal artery thrombosis,
      previously associated with injectable collagen, has not been seen with newer
      fillers. CONCLUSIONS: Injectable nonpermanent fillers are extremely safe
      substances. Attention to injection technique further minimizes the low risk of
      adverse events, which are usually minor, spontaneously resolving, and easily
      treated.

PMID- 18090349
TI  - Modification of acute cardiovascular homeostatic responses to hemorrhage
      following mild to moderate traumatic brain injury.
AB  - OBJECTIVES: The cardiovascular homeostatic responses to hemorrhage are
      coordinated in the central nervous system. Coincidental brain injury, which is
      present in 64% of trauma patients, could impair these responses. Our objective
      was to test the hypothesis that mild to moderate traumatic brain injury alters
      cardiovascular reflex responses to acute hemorrhage. DESIGN: Experimental
      prospective, randomized study in terminally anesthetized rats. SETTING:
      Experimental laboratory of university. SUBJECTS: Twenty-four male Wistar rats
      weighing 240-260 g. INTERVENTIONS: Brain injury was induced using the lateral
      fluid percussion injury model in anesthetized rats. The fluid percussion device
      delivered an applied cortical pressure of 1.2 atm and 1.8 atm, producing mild and
      moderate injury, respectively. Control animals underwent identical surgical
      procedures but with no applied cortical pressure. Hemorrhage was carried out 10
      mins after brain injury, at a rate of 2% of blood volume per minute until 40%
      blood volume was withdrawn. MEASUREMENTS AND MAIN RESULTS: The effects of acute
      traumatic brain injury on the biphasic heart rate and mean arterial blood
      pressure response to hemorrhage were studied. Traumatic brain injury attenuated
      the normal bradycardic response and delayed the hypotensive response to
      hemorrhage. This effect was graded according to the severity of brain injury. In
      mild injury, the depressor phase was delayed, but the biphasic pattern of heart
      rate response was maintained. No mortality was observed in this group. Following
      moderate brain injury, marked attenuation of the biphasic heart rate and mean
      arterial blood pressure response (p < .001 and p = .0007) was observed. Fifty
      percent of this group died within 90 mins of hemorrhage completion. Significant
      differences in the biphasic response were observed between survivors and
      nonsurvivors (p = .013, p = .001, respectively). In nonsurvivors, the biphasic
      response was abolished. CONCLUSIONS: Acute mild and moderate traumatic brain
      injury disrupts cardiovascular homeostatic responses to extracranial hemorrhage;
      this disruption is graded according to the severity of traumatic brain injury.
      Severe disruption is associated with an increase in early mortality.

PMID- 18090350
TI  - Oxygen saturation determined from deep muscle, not thenar tissue, is an early
      indicator of central hypovolemia in humans.
AB  - OBJECTIVE: To compare the responses of noninvasively measured tissue oxygen
      saturation (StO2) and calculated muscle oxygen tension (PmO2) to standard
      hemodynamic variables for early detection of imminent hemodynamic instability
      during progressive central hypovolemia in humans. DESIGN: Prospective study.
      SETTING: Research laboratory. SUBJECTS: Sixteen healthy human volunteers.
      INTERVENTIONS: Progressive lower body negative pressure (LBNP) to onset of
      cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Noninvasive measurements
      of blood pressures, heart rate, and stroke volume were obtained during
      progressive LBNP with simultaneous assessments of StO2, PmO2, and muscle oxygen
      saturation (SmO2). Forearm SmO2 and PmO2 were determined with a novel near
      infrared spectroscopic measurement device (UMMS) and compared with thenar StO2
      measured by a commercial device (HT). All values were normalized to the duration
      of LBNP exposure required for cardiovascular collapse in each subject (i.e., LBNP
      maximum). Stroke volume was significantly decreased at 25% of LBNP maximum,
      whereas blood pressure was a late indicator of imminent cardiovascular collapse.
      PmO2 (UMMS) was significantly decreased at 50% of maximum LBNP while SmO2 (UMMS)
      decreased at 75% of maximum LBNP. Thenar StO2 (HT) showed no statistical change
      throughout the entire LBNP protocol. CONCLUSIONS: Spectroscopic assessment of
      forearm muscle PO2 and SmO2 provides noninvasive and continuous measures that are
      early indicators of impending cardiovascular collapse resulting from progressive
      reductions in central blood volume.

PMID- 18090351
TI  - Diagnostic bronchoscopy in hematology and oncology patients with acute
      respiratory failure: prospective multicenter data.
AB  - OBJECTIVE: To describe the diagnostic yields of test strategies with and without
      fiberoptic bronchoscopy and bronchoalveolar lavage (FO-BAL), as well as outcomes,
      in cancer patients with acute respiratory failure (ARF). DESIGN: Prospective
      observational study. SETTING: Fifteen intensive care units in France. PATIENTS:
      In all, 148 cancer patients, including 45 bone marrow transplant recipients (27
      allogeneic, 18 autologous) with hypoxemic ARF. INTERVENTION: None. RESULTS:
      Overall, 146 causes of ARF were identified in 128 patients (97 [66.4%] pulmonary
      infections). The cause of ARF was identified in 50.5% of the 101 patients who
      underwent FO-BAL and in 66.7% of the other patients. FO-BAL was the only
      conclusive test in 34 (33.7%) of the 101 investigated patients. Respiratory
      status deterioration after FO-BAL occurred in 22 of 45 (48.9%) nonintubated
      patients, including 16 (35.5%) patients who required ventilatory support.
      Hospital mortality was 55.4% (82 deaths) overall and was not significantly
      different in the groups with and without FO-BAL. By multivariate analysis,
      mortality was affected by characteristics of the malignancy (remission,
      allogeneic bone marrow transplantation), cause of ARF (ARF during neutropenia
      recovery, cause not identified), and need for life-sustaining treatments
      (mechanical ventilation and vasopressors). CONCLUSION: In critically ill cancer
      patients with ARF, a diagnostic strategy that does not include FO-BAL may be as
      effective as FO-BAL without exposing the patients to respiratory status
      deterioration.

PMID- 18090352
TI  - Increasing amiodarone use in cardiopulmonary resuscitation: an analysis of the
      National Registry of Cardiopulmonary Resuscitation.
AB  - OBJECTIVE: To examine practice patterns of amiodarone use during in-hospital
      cardiac arrest. This study addresses the changing pattern of amiodarone use over
      time, following the publication of landmark studies and the inclusion of
      amiodarone in the American Heart Association Guidelines for Cardiopulmonary
      Resuscitation and Emergency Cardiovascular Care. Furthermore, this study examines
      the impact of hospital and patient specific factors on the use of amiodarone.
      DESIGN: Retrospective cohort study, using the National Registry for
      Cardiopulmonary Resuscitation, an international registry of in-hospital
      resuscitation events. PATIENTS: All patients with an in-hospital ventricular
      fibrillation (VF) or pulseless ventricular tachycardia (pVT) event reported to
      the national registry from January 1, 2000, to July 31, 2005. MEASUREMENTS AND
      MAIN RESULTS: During the study period, 14,854 of 29,552 (50%) adults (> 18 yrs
      old) with VF/pVT received an antiarrhythmic drug; 8,883 (60%) of these patients
      received amiodarone. In adults, amiodarone use for VF/pVT increased from 25% in
      2000 to 72% in 2005 (p < .0001). Among children, 270 of 553 (49%) VF/pVT episodes
      were treated with an antiarrhythmic drug; 108 (40%) of these patients received
      amiodarone. Adults in institutions with larger intensive care units (> 50 beds)
      were more likely than those in institutions with smaller intensive care units (<
      or = 50 beds) to receive amiodarone; the association persisted in multivariable
      analysis (odds ratio [OR] = 1.825; 95% confidence interval [CI], 1.694-1.966).
      Thirty five percent of adults with VF/pVT who received amiodarone also received
      lidocaine, while 67% of children who received amiodarone also received lidocaine
      (p < .001). It is not possible to determine from the database the order in which
      medications were administered. CONCLUSIONS: There has been a significant increase
      in amiodarone use for VF/pVT events over the past 5 yrs. The frequency of
      amiodarone use in adults correlated positively with the number of intensive care
      beds. These results suggest that emerging data and national guidelines affect
      resuscitation practice patterns.

PMID- 18090355
TI  - Feasibility study of cytokine removal by hemoadsorption in brain-dead humans.
AB  - BACKGROUND: Inflammatory cytokines occur in the circulation and in the tissues
      after brain death and have been associated with dysfunction of donor organs
      before and after transplantation. OBJECTIVE: To determine the feasibility of
      removing cytokines using a hemoadsorption device. DESIGN: Two-center, randomized,
      open-label, feasibility study in which brain-dead subjects were randomized to two
      treatment groups. SETTING: Two U.S. academic hospitals. PARTICIPANTS: Eight brain
      dead subjects deemed unsuitable for organ donation by respective organ
      procurement organizations. MAIN OUTCOME MEASURES: After obtaining consent from
      families, subjects were treated with hemoadsorption for 4 hrs using CytoSorb.
      Effects on cytokines (tumor necrosis factor, interleukin [IL]-6, and IL-10) were
      assessed both across the device and in the plasma over time. Feasibility for
      cytokine removal was assessed using objective criteria. RESULTS: Cytokine removal
      across the CytoSorb device ranged from 4% to 30% and was not significantly
      different from 1 hr to 4 hrs. Overall removal was greatest for IL-6, 28% (p =
      .006), and least for tumor necrosis factor, 8.5% (p = .13). Plasma concentrations
      of both IL-6 and tumor necrosis factor, but not IL-10, were significantly reduced
      after the first hour of therapy; mean differences were -13% +/- 7% for IL-6 (p =
      .039), -23% +/- 9% for tumor necrosis factor (p = .02), and -2% +/- 7% of IL-10
      (p = 23). However, plasma concentrations for all three cytokines increased over
      time and were above baseline by the end of the intervention. No adverse effects
      of therapy were observed. However, removal of cortisol and triiodothyronine was
      similar to removal of cytokines. CONCLUSIONS: Hemoadsorption for removal of
      cytokines in brain-dead subjects is feasible. Evaluation of possible clinical
      benefit will require controlled trials in actual donors. However, the significant
      capacity for cytokine removal and absence of adverse events suggest that such
      trials are warranted.

PMID- 18090356
TI  - Effect of hyperoxia on regional oxygenation and metabolism after severe traumatic
      brain injury: preliminary findings.
AB  - OBJECTIVE: To determine the effect of normobaric hyperoxia on cerebral metabolism
      in patients with severe traumatic brain injury. DESIGN: Prospective clinical
      investigation. SETTING: Neurosciences critical care unit of a university
      hospital. PATIENTS: Eleven patients with severe traumatic brain injury.
      INTERVENTIONS: Cerebral microdialysis, brain tissue oximetry (PbO2), and oxygen
      15 positron emission tomography (15O-PET) were undertaken at normoxia and
      repeated at hyperoxia (FiO2 increase of between 0.35 and 0.50). MEASUREMENTS AND
      MAIN RESULTS: Established models were used to image cerebral blood flow, blood
      volume, oxygen metabolism, and oxygen extraction fraction. Physiology was
      characterized in a focal region of interest (surrounding the microdialysis
      catheter) and correlated with microdialysis and oximetry. Physiology was also
      characterized in a global region of interest (including the whole brain), and a
      physiologic region of interest (defined using a critical cerebral metabolic rate
      of oxygen threshold). Hyperoxia increased mean +/- sd PbO2 from 28 +/- 21 mm Hg
      to 57 +/- 47 mm Hg (p = .015). Microdialysate lactate and pyruvate were
      unchanged, but the lactate/pyruvate ratio showed a statistically significant
      reduction across the study population (34.1 +/- 9.5 vs. 32.5 +/- 9.0, p = .018).
      However, the magnitude of reduction was small, and its clinical significance
      doubtful. The focal region of interest and global 15O-PET variables were
      unchanged. "At-risk" tissue defined by the physiologic region of interest,
      however, showed a universal increase in cerebral metabolic rate of oxygen from a
      median (interquartile range) of 23 (22-25) micromol x 100 mL(-1) x min(-1) to 30
      (28-36) micromol x 100 mL(-1) x min(-1) (p < .01). CONCLUSIONS: In severe
      traumatic brain injury, hyperoxia increases PbO2 with a variable effect on
      lactate and lactate/pyruvate ratio. Microdialysis does not, however, predict the
      universal increases in cerebral metabolic rate of oxygen in at-risk tissue, which
      imply preferential metabolic benefit with hyperoxia.

PMID- 18090357
TI  - Electrocardiogram waveforms for monitoring effectiveness of chest compression
      during cardiopulmonary resuscitation.
AB  - BACKGROUND: Newer guidelines address the importance of effective chest
      compressions, citing evidence that this primary intervention is usually
      suboptimally performed during cardiopulmonary resuscitation. We therefore sought
      a readily available option for monitoring the effectiveness of chest
      compressions, specifically using the electrocardiogram. METHODS AND RESULTS:
      Ventricular fibrillation was induced by coronary artery occlusion and untreated
      for 5 mins. Male domestic pigs weighing 40 +/- 2 kg were randomized to optimal or
      suboptimal chest compressions after onset of ventricular fibrillation. Optimal
      depth of mechanical compression in six animals was defined as a decrease of 25%
      in anterior posterior diameter of the chest during compression. Suboptimal
      compression, also in six animals, was defined as a decrease of 17.5% in anterior
      posterior diameter. For each group, the chest compressions were maintained at a
      rate of 100 per min. After 3 mins of chest compression, defibrillation was
      attempted with a 150-J biphasic shock. All animals had return of spontaneous
      circulation after optimal compressions. This contrasted with suboptimal
      compressions, after which none of the animals had return of spontaneous
      circulation. Amplitude spectrum area values, representing the
      electrocardiographic amplitude frequency spectral area computed from conventional
      precordial leads, like coronary perfusion pressure and end tidal PCO2, were
      predictive of outcomes. CONCLUSION: The effectiveness of chest compressions was
      reflected in the amplitude spectrum area values. Accordingly, the amplitude
      spectrum area predictor may be incorporated in current automated external
      defibrillators to monitor and prompt the effectiveness of chest compression
      during cardiopulmonary resuscitation.

PMID- 18090359
TI  - Identifying potentially shockable rhythms without interrupting cardiopulmonary
      resuscitation.
AB  - OBJECTIVE: Current versions of automated external defibrillators (AEDs) mandate
      interruptions of chest compression for rhythm analyses because of artifacts
      produced by chest compressions. Interruption of chest compressions reduces
      likelihood of successful resuscitation by as much as 50%. We sought a method to
      identify a shockable rhythm without interrupting chest compressions during
      cardiopulmonary resuscitation (CPR). DESIGN: Experimental study. SETTING: Weil
      Institute of Critical Care Medicine, Rancho Mirage, CA. SUBJECTS: None.
      INTERVENTIONS: Electrocardiographs (ECGs) were recorded in conjunction with AEDs
      during CPR in human victims. A shockable rhythm was defined as disorganized
      rhythm with an amplitude > 0.1 mV or, if organized, at a rate of > or = 180
      beats/min. Wavelet-based transformation and shape-based morphology detection were
      used for rhythm classification. Morphologic consistencies of waveform
      representing QRS components were analyzed to differentiate between disorganized
      and organized rhythms. For disorganized rhythms, the amplitude spectrum area was
      computed in the frequency domain to distinguish between shockable ventricular
      fibrillation and nonshockable asystole. For organized rhythms, in victims in whom
      the absence of a heartbeat was independently confirmed, the heart rate was
      estimated for further classification. MEASUREMENTS AND MAIN RESULTS: To derive
      the algorithm, we used 29 recordings on 29 patients from the Creighton University
      ventricular tachyarrhythmia database. For validation, the algorithm was tested on
      an independent population of 229 victims, including recordings of both ECG and
      depth of chest compressions obtained during suspected out-of-hospital sudden
      death. The recordings included 111 instances in which the ECG was corrupted
      during chest compressions. A shockable rhythm was identified with a sensitivity
      of 93% and a specificity of 89%, yielding a positive predictive value of 91%. A
      nonshockable rhythm was identified with a sensitivity of 89%, a specificity of
      93%, and a positive predictive value of 91% during uninterrupted chest
      compression. CONCLUSIONS: The algorithm fulfilled the potential lifesaving
      advantages of allowing for uninterrupted chest compression, avoiding pauses for
      automated rhythm analyses before prompting delivery of an electrical shock.

PMID- 18090358
TI  - Estradiol is associated with mortality in critically ill trauma and surgical
      patients.
AB  - OBJECTIVE: Sexual dimorphism (variation in outcome related to sex) after trauma
      hemorrhage and sepsis is well documented in animals, with the pro-estrus state
      being proinflammatory and associated with a survival advantage. Although some
      observational studies confirm this pattern in humans, others demonstrate no
      difference in mortality. Estrogens are important modulators of the inflammatory
      response and insulin resistance in humans and have been linked to increased
      mortality during sepsis. Our objective was to determine whether sex hormone
      levels were associated with outcomes in critically ill surgical patients. DESIGN:
      Prospective cohort. PATIENTS: A total of 301 adult critically ill or injured
      surgical patients remaining in the intensive care unit for > or = 48 hrs at two
      academic medical centers. INTERVENTIONS: None. MEASUREMENTS: Blood was collected
      48 hrs after intensive care unit admission and assayed for sex hormones
      (estradiol, testosterone, prolactin, and progesterone) and cytokines (tumor
      necrosis factor-alpha and interleukin-1, -2, -4, -6, -8, and -10). Demographic
      and outcome data were also collected. MAIN RESULTS: Estradiol was significantly
      higher in nonsurvivors (p < .001). Analysis by quartiles of estradiol
      demonstrated greater than a three-fold increase in the mortality rate for the
      highest vs. the lowest estradiol quartiles (29% vs. 8%, p < .001). Estradiol was
      also higher in nonsurvivors. An estradiol level of 100 pg/mL was associated with
      an odds ratio for death of 4.60 (95% confidence interval, 1.56-13.0) compared
      with a reference estradiol level of 45 pg/mL. CONCLUSIONS: We conclude that serum
      estradiol correlates with mortality in critically ill and injured surgical
      patients and discuss potential mechanisms for this observation.

PMID- 18090362
TI  - Inhibiting nitric oxide overproduction during hypotensive sepsis increases local
      oxygen consumption in rat skeletal muscle.
AB  - OBJECTIVE: Although nitric oxide (NO) is a known regulator of cardiovascular
      function, the effect of NO overproduction during sepsis on capillary oxygen
      transport and local tissue oxygen consumption is not well understood. The
      objectives of this study were to determine whether sepsis-induced NO
      overproduction increased capillary stopped-flow and modulated tissue oxygen
      consumption in skeletal muscle. DESIGN: Prospective, controlled laboratory study.
      SETTING: Animal laboratory in a university-affiliated research institute.
      SUBJECTS: Male Sprague-Dawley rats, 165-180 g body weight. INTERVENTIONS: Rats
      were made septic by cecal ligation and perforation (CLP) and were then ventilated
      and volume resuscitated (saline). The hind limb extensor digitorum longus (EDL)
      skeletal muscle was blunt dissected for in vivo microvascular imaging. The
      inducible NO synthase (iNOS) inhibitor L-N6-(1-iminoethyl)lysine dihydrochloride
      (L-NIL) was infused (3 mg/kg body weight per hour) starting 1 hr post-CLP to
      maintain arterial blood and EDL tissue NO(x)(-) (NO2(-) + NO3(-)) at baseline.
      MEASUREMENTS AND MAIN RESULTS: Red blood cell hemodynamics, hemoglobin oxygen
      saturation, capillary geometry, and functional capillary density information were
      used to calculate capillary oxygen flux (the rate of oxygen diffusion from
      capillary to tissue) and indices of local oxygen delivery and tissue oxygen
      consumption. Over the first 5 hrs of septic injury, mean arterial pressure
      decreased while capillary stopped-flow and capillary oxygen flux both increased
      (p < .05). Inhibiting iNOS/NO overproduction partially restored mean arterial
      pressure and increased arterial pH. Within the microcirculation, inhibiting NO
      increased capillary red cell velocity and increased local tissue oxygen
      consumption (p < .05). Inhibiting NO failed, however, to prevent capillary
      stopped-flow. CONCLUSIONS: During the onset of sepsis, concurrent with the onset
      of microvascular dysfunction, there is an iNOS/NO-mediated reduction in local
      skeletal muscle tissue oxygen consumption.

PMID- 18090363
TI  - Pulmonary morphofunctional effects of mechanical ventilation with high
      inspiratory air flow.
AB  - OBJECTIVE: Uncertainties about the numerous degrees of freedom in ventilator
      settings leave many unanswered questions about the biophysical determinants of
      lung injury. We investigated whether mechanical ventilation with high air flow
      could yield lung mechanical stress even in normal animals. DESIGN: Prospective,
      randomized, controlled experimental study. SETTING: University research
      laboratory. SUBJECTS: Thirty normal male Wistar rats (180-230 g). INTERVENTIONS:
      Rats were ventilated for 2 hrs with tidal volume of 10 mL/kg and either with
      normal inspiratory air flow (V') of 10 mL/s (F10) or high V' of 30 mL/s (F30). In
      the control group, animals did not undergo mechanical ventilation. Because high
      flow led to elevated respiratory rate (200 breaths/min) and airway peak
      inspiratory pressure (PIP,aw = 17 cm H2O), two additional groups were established
      to rule out the potential contribution of these variables: a) normal respiratory
      rate = 100 breaths/min and V' = 30 mL/sec; and b) PIP,aw = 17 cm H2O and V' = 10
      mL/sec. MEASUREMENTS AND MAIN RESULTS: Lung mechanics and histology (light and
      electron microscopy), arterial blood gas analysis, and type III procollagen
      messenger RNA expression in lung tissue were analyzed. Ultrastructural microscopy
      was similar in control and F10 groups. High air flow led to increased lung
      plateau and peak pressures, hypoxemia, alveolar hyperinflation and collapse,
      pulmonary neutrophilic infiltration, and augmented type III procollagen messenger
      RNA expression compared with control rats. The reduction of respiratory rate did
      not modify the morphofunctional behavior observed in the presence of increased
      air flow. Even though the increase in peak pressure yielded mechanical and
      histologic changes, type III procollagen messenger RNA expression remained
      unaltered. CONCLUSIONS: Ventilation with high inspiratory air flow may lead to
      high tensile and shear stresses resulting in lung functional and morphologic
      compromise and elevation of type III procollagen messenger RNA expression.

PMID- 18090365
TI  - Postresuscitation myocardial diastolic dysfunction following prolonged
      ventricular fibrillation and cardiopulmonary resuscitation.
AB  - OBJECTIVE: Postresuscitation myocardial dysfunction is one of the leading causes
      of early death after successful resuscitation from sudden death. However, the
      diastolic characteristics of postresuscitation myocardial dysfunction are not
      well defined. We therefore investigated the postresuscitation left ventricular
      diastolic function following prolonged cardiac arrest and subsequent
      cardiopulmonary resuscitation. DESIGN: Prospective, observational animal study.
      SETTING: Medical research laboratory in a university-affiliated research and
      educational institute. SUBJECTS: Domestic pigs. INTERVENTIONS: Seven anesthetized
      pigs (40 +/- 4 kg) were studied before and after 7 mins of untreated occlusive
      ventricular fibrillation induced cardiac arrest. Ejection fraction, early and
      atrial peak transmitral flow velocities, deceleration time of early transmitral
      flow velocity, myocardial performance index, peak Emax and Amax mitral annulus
      velocities by Doppler tissue imaging, and early diastolic left ventricular flow
      propagation velocity were measured at baseline; 60, 120, 180, and 240 mins; and
      72 hrs after resuscitation. MEASUREMENTS AND MAIN RESULTS: Five animals were
      successfully resuscitated. Left ventricular ejection fraction, E(m)/A(m) ratio,
      and propagation velocity were significantly decreased, and myocardial performance
      index was significantly increased compared with baseline measurements. Left
      ventricular diastolic and systolic function returned to baseline level at 72 hrs
      postresuscitation. CONCLUSIONS: Left ventricular systolic dysfunction was
      significantly impaired after cardiac arrest and cardiopulmonary resuscitation, as
      previously demonstrated. This was associated with a profound left ventricular
      diastolic dysfunction. However, this postresuscitation left ventricular systolic
      and diastolic myocardial dysfunction was reversible after 72 hrs in this
      experimental model of ventricular fibrillation cardiac arrest.

PMID- 18090367
TI  - Natural history of disseminated intravascular coagulation diagnosed based on the
      newly established diagnostic criteria for critically ill patients: results of a
      multicenter, prospective survey.
AB  - OBJECTIVE: To survey the natural history of disseminated intravascular
      coagulation (DIC) in patients diagnosed according to the Japanese Association for
      Acute Medicine (JAAM) DIC scoring system in a critical care setting. DESIGN:
      Prospective, multicenter study during a 4-month period. SETTING: General critical
      care center in a tertiary care hospital. PATIENTS: All patients were enrolled
      when they were diagnosed as DIC by the JAAM DIC scoring system. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Platelet counts, prothrombin time ratio,
      fibrinogen, and fibrin/fibrinogen degradation products were measured, and the
      systemic inflammatory response syndrome criteria met by the patients were
      determined following admission. Of 3,864 patients, 329 (8.5%) were diagnosed with
      DIC and the 28-day mortality rate was 21.9%, which was significantly different
      from that of the non-DIC patients (11.2%) (p < .0001). The progression of
      systemic inflammation, deterioration of organ function, and stepwise increase in
      incidence of the International Society on Thrombosis and Haemostasis (ISTH) DIC
      and its scores all correlated with an increase in the JAAM DIC score as
      demonstrated by the patients on day 0. There were significant differences in the
      JAAM DIC score and the variables adopted in the scoring system between survivors
      and nonsurvivors. The logistic regression analyses showed the JAAM DIC score and
      prothrombin time ratio on the day of DIC diagnosis to be predictors of patient
      outcome. The patients who simultaneously met the ISTH DIC criteria demonstrated
      twice the incidence of multiple organ dysfunction (61.1 vs. 30.5%, p < .0001) and
      mortality rate (34.4 vs. 17.2%, p = .0015) compared with those without the ISTH
      DIC diagnosis. CONCLUSIONS: This prospective survey demonstrated the natural
      history of DIC patients diagnosed by the JAAM DIC diagnostic criteria in a
      critical care setting. The study provides further evidence of a progression from
      the JAAM DIC to the ISTH overt DIC.

PMID- 18090368
TI  - A pilot study to detect high mobility group box 1 and heat shock protein 72 in
      cerebrospinal fluid of pediatric patients with meningitis.
AB  - OBJECTIVE: To determine whether cerebrospinal fluid (CSF) levels of high mobility
      group box 1 (HMGB1) or heat shock protein 72 (Hsp72) are elevated in patients
      with meningitis. DESIGN: Prospective study of four cohorts of patients. SETTING:
      Intensive care unit and infectious disease clinic of pediatrics at the Xiangya
      Hospital. PATIENTS: A total of 104 children (13 with bacterial meningitis, 38
      with aseptic meningitis, 7 with tuberculous meningitis, and 46 without
      meningitis). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At the time of
      admission, CSF samples were obtained from 104 patients with suspected meningitis
      and examined for the presence of invading pathogens, changes in CSF white blood
      cell counts, and protein and/or glucose concentrations. Based on CSF parameters,
      13, 38, and 7 patients were diagnosed as having bacterial, aseptic, and
      tuberculous meningitis, respectively. All CSF samples were assayed for HMGB1 or
      Hsp72 using semiquantitative Western blot analysis. CSF levels of HMGB1 were
      elevated in patients with bacterial meningitis or aseptic meningitis but were
      four times higher in patients with bacterial meningitis vs. aseptic meningitis.
      There was a significant correlation between CSF HMGB1 levels and CSF white blood
      cell counts and glucose levels in patients with bacterial meningitis. Similarly,
      CSF levels of Hsp72 were significantly elevated in patients with bacterial
      meningitis or tuberculous meningitis and correlated well with CSF white blood
      cell counts in patients with bacterial meningitis or tuberculous meningitis.
      CONCLUSIONS: CSF levels of HMGB1 and Hsp72 were significantly higher in patients
      with bacterial meningitis than those with aseptic meningitis and correlated well
      with CSF white blood cell counts in patients with bacterial (but not aseptic)
      meningitis.

PMID- 18090369
TI  - Extravascular lung water in sepsis-associated acute respiratory distress
      syndrome: indexing with predicted body weight improves correlation with severity
      of illness and survival.
AB  - OBJECTIVES: To determine whether extravascular lung water predicts survival in
      patients with early acute respiratory distress syndrome, to determine the
      relationship between extravascular lung water and other markers of lung injury,
      and to examine if indexing extravascular lung water with predicted body weight
      (EVLWp) strengthens its discriminative power. DESIGN: Extravascular lung water
      and other markers of lung injury were measured prospectively in 19 patients with
      sepsis-induced acute respiratory distress syndrome for 3 days. SETTING: The
      intensive care units of an academic tertiary referral hospital. MEASUREMENTS AND
      MAIN RESULTS: Lung injury score, Sequential Organ Failure Assessment score, dead
      space-tidal volume fraction (Vd/Vt), and EVLWp were all significantly higher on
      day 1 in nonsurvivors compared with survivors (lung injury score, 2.8 +/- 0.34
      vs. 1.9 +/- 0.50; p = .004) (Sequential Organ Failure Assessment score, 13 +/-
      3.4 vs. 7.7 +/- 0.8; p = .006) (Vd/Vt, 0.68 +/- 0.07 vs. 0.58 +/- 0.07; p = .009)
      (EVLWp, 20.6 +/- 4.6 vs. 11.6 +/- 1.9 mL/kg; p = .002). EVLWp correlated with
      Sequential Organ Failure Assessment score, lung injury score, Vd/Vt, and
      PaO2/FIO2. The receiver operator characteristic curve analysis indicated that
      EVLWp, Vd/Vt, and extravascular lung water (p = .0005, .009, and .013,
      respectively) but not PaO2/FIO2 (p = .311) discriminate between survivors and
      nonsurvivors. Three-day average EVLWp >16 mL/kg predicted in-hospital mortality
      with 100% specificity and 86% sensitivity. CONCLUSIONS: Increased extravascular
      lung water is a feature of early acute respiratory distress syndrome and predicts
      survival. Indexing extravascular lung water to predicted body weight, instead of
      actual body weight, improves the predictive value of extravascular lung water for
      survival and correlation with markers of disease severity.

PMID- 18090370
TI  - Gas exchange and lung inflammation using nasal intermittent positive-pressure
      ventilation versus synchronized intermittent mandatory ventilation in piglets
      with saline lavage-induced lung injury: an observational study.
AB  - OBJECTIVE: Physiologic and pathologic comparison of two modes of assisted
      ventilation, nasal intermittent positive-pressure ventilation (NIPPV) and
      synchronized intermittent mandatory ventilation (SIMV), in spontaneously
      breathing term newborn piglets with saline lavage-induced lung injury. DESIGN:
      After inducing acute lung injury via repetitive saline lavage, piglets were
      randomized to NIPPV (n = 12) or SIMV (n = 11) and treated for 6 hrs. SETTING:
      Clinical laboratory. SUBJECTS: Spontaneously breathing term newborn piglets.
      INTERVENTIONS: Invasive (SIMV) or noninvasive (NIPPV) assisted ventilation for 6
      hrs. MEASUREMENTS: Physiologic parameters and arterial blood gases were
      continuously monitored. At the conclusion of the study, lung tissue was obtained
      to analyze for evidence of inflammation, including myeloperoxidase, interleukin
      8, and hydrogen peroxide levels, as well as for evidence of pathologic injury.
      MAIN RESULTS: Piglets treated with NIPPV demonstrated higher arterial blood gas
      pH (p < .001), lower PaCO2 (p < .05), and a lower set respiratory rate (p <
      .0001) as compared with the SIMV-treated piglets. The piglets in the SIMV group
      had higher PaO2/PaO2 ratio than those in the NIPPV group (p = .001). There was
      significantly more interstitial inflammation (p = .04) in the SIMV-treated
      piglets compared with the NIPPV-treated piglets. Total respiratory rate, heart
      rate, blood pressure, oxygen saturation, and biochemical markers of lung
      inflammation were not different between the groups. CONCLUSION: In surfactant
      deficient term newborn piglets, NIPPV offers an effective and noninvasive
      ventilatory strategy with the potential for less pathologic lung inflammation.

PMID- 18090371
TI  - Mortality risk and length of stay associated with self-inflicted burn injury:
      evidence from a national sample of 30,382 adult patients.
AB  - OBJECTIVE: Existing studies report contradictory findings regarding
      characteristics and outcomes of patients admitted with self-inflicted burn
      injuries. The objective of this study was to report demographic and medical
      characteristics of patients admitted to burn centers with self-inflicted burn
      injuries and to assess mortality risk and length of stay compared with patients
      whose injuries were not self-inflicted. DESIGN: Retrospective, cohort study.
      SETTING: A total of 70 burn centers from the United States that contributed data
      to the American Burn Association National Burn Repository. PATIENTS: A total of
      30,382 adult patients (593 with self-inflicted injuries) who were admitted with a
      thermal injury from 1995 through 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Demographics, comorbidities, burn injury severity variables (total body
      surface area burned [TBSA], TBSA burned third degree, inhalation injury),
      hospital mortality, intensive care length of stay, and total hospital length of
      stay were ascertained. Patients with self-inflicted injuries had larger TBSA
      burned (32.0% vs. 12.8%, p < .01) and larger third-degree TBSA burned (20.6% vs.
      4.9%, p < .01) and were more likely to incur an inhalation injury (37.3% vs.
      12.8%, p < .01). Before matching, patients with self-inflicted injuries were at
      greater risk of mortality (23.6% vs. 6.8%, p < .01) and required longer intensive
      care (median of 4 days vs. 0 days, p < .01) and total hospital stays (median of
      23 days vs. 8 days, p < .01). After propensity score matching on demographic,
      medical, and burn injury variables, they were not more likely to die of their
      injuries (23.6% vs. 23.1%, p = .84), did not require longer intensive care stays
      (4 days vs. 3 days, p = .75), and did not require longer total hospital stays (23
      days vs. 18 days, p = .50). CONCLUSIONS: Compared with patients with similar
      demographic, health, and injury characteristics whose injuries are not self
      inflicted, patients with self-inflicted burn injuries are not at greater risk of
      mortality and do not require longer durations of intensive care or total
      hospitalization.

PMID- 18090372
TI  - Efficacy of the bovine antimicrobial peptide indolicidin combined with
      piperacillin/tazobactam in experimental rat models of polymicrobial peritonitis.
AB  - OBJECTIVE: To investigate the efficacy of piperacillin/tazobactam combined with
      indolicidin in the prevention of lethality in two rat models of polymicrobial
      peritonitis. DESIGN: Prospective, randomized, controlled animal study. SETTING:
      Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats.
      INTERVENTIONS: Adult male Wistar rats were given an intraperitoneal injection of
      1 mg of Escherichia coli 0111:B4 lipopolysaccharide or had intraabdominal sepsis
      induced by cecal ligation and puncture. For each model, all animals were
      randomized to receive isotonic sodium chloride solution intraperitoneally, 1
      mg/kg indolicidin, 120 mg/kg piperacillin/tazobactam, and 1 mg/kg indolicidin
      combined with 120 mg/kg piperacillin/tazobactam. Each group included 20 animals.
      MEASUREMENTS AND MAIN RESULTS: Main outcome measures were: bacterial growth in
      blood, peritoneum, spleen, liver, and mesenteric lymph nodes; endotoxin,
      interleukin-6, and tumor necrosis factor-alpha concentrations in plasma; and
      lethality. All compounds reduced significantly bacterial growth and lethality
      compared with saline treatment. Treatment with indolicidin resulted in
      significant decrease in plasma endotoxin and cytokine levels, whereas
      piperacillin/tazobactam exerted the opposite effect. The combination between
      indolicidin and piperacillin/tazobactam proved to be the most effective treatment
      in reducing all variables measured. CONCLUSION: Indolicidin may have potential
      therapeutic usefulness alone and when associated with piperacillin/tazobactam in
      polymicrobial peritonitis.

PMID- 18090373
TI  - Effects of aspirin, nimesulide, and SC-560 on vasopressin-induced contraction of
      human gastroepiploic artery and saphenous vein.
AB  - OBJECTIVE: The present experiments were designed to evaluate differences in the
      effects of cyclooxygenase (COX)-1 and COX-2 inhibition on contractile responses
      of human gastroepiploic artery and saphenous vein elicited by vasopressin.
      DESIGN: Laboratory investigation. SETTING: University laboratory. SUBJECTS: Rings
      of human gastroepiploic artery were obtained from 32 patients undergoing
      gastrectomy, and rings of saphenous vein were obtained from 30 patients
      undergoing coronary artery bypass surgery. INTERVENTIONS: The rings were
      suspended in organ baths for isometric recording of tension. We studied the
      responses to vasopressin in the absence and in the presence of either the
      vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP or the COX inhibitors
      aspirin, nimesulide, or SC-560. MEASUREMENTS AND MAIN RESULTS: Vasopressin (10(
      11)-10(-6) mol/L) produced concentration-dependent contractions with an EC50
      value of 4.3 x 10(-10) mol/L for gastroepiploic artery and 3.4 x 10(-8) mol/L for
      saphenous vein. The vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (10(-7)
      mol/L) induced significant shifts (p < .001) of the control curves to the right.
      The COX-1 and COX-2 inhibitor aspirin (10(-6)-10(-5) mol/L) and the COX-2
      inhibitor nimesulide (10(-6) mol/L) induced leftward shifts of the concentration
      response curve for vasopressin in gastroepiploic artery. Lower concentrations of
      aspirin or the COX-1 inhibitor SC-560 (10(-8) mol/L) did not affect the responses
      of gastroepiploic artery. COX-1 or COX-2 inhibition did not modify the
      contraction of saphenous vein to vasopressin. CONCLUSION: The results provide
      functional evidence that aspirin at high concentrations and the COX-2 selective
      inhibitor nimesulide potentiate the contractile response of gastroepiploic artery
      to vasopressin, thus suggesting the release of relaxant prostaglandins by the
      peptide. However, contractions of human saphenous vein were unaffected by COX
      inhibition, indicating that vasopressin does not stimulate the release of
      prostanoids. The amplifying effect of aspirin on vasopressin-induced contraction
      may contribute to early graft failure when the gastroepiploic artery is used as a
      coronary artery bypass graft.

PMID- 18090374
TI  - Melatonin receptors mediate improvements of liver function but not of hepatic
      perfusion and integrity after hemorrhagic shock in rats.
AB  - OBJECTIVE: Melatonin has been demonstrated to attenuate organ damage in models of
      ischemia and reperfusion. Melatonin treatment before hemorrhagic shock has been
      shown to improve liver function and hepatic perfusion. Proposed mechanisms of the
      pineal hormone involve direct inactivation of reactive oxygen species and
      induction of antioxidative enzymes. However, recent evidence suggests a strong
      influence of melatonin receptor activation for these effects. Specific protection
      of organ function by melatonin after hemorrhage has not been investigated yet. In
      this study, we evaluated whether melatonin therapy after hemorrhagic shock
      improves liver function and hepatic perfusion, with emphasis on melatonin
      receptor activation. DESIGN: Prospective, randomized, controlled study. SETTING:
      University research laboratory. SUBJECTS: Male Sprague-Dawley rats, 200-300 g (n
      = 10 per group). INTERVENTIONS: Animals underwent hemorrhagic shock (mean
      arterial pressure, 35 +/- 5 mm Hg for 90 mins) and were resuscitated with shed
      blood and Ringer's solution. At the end of shock, animals were treated with
      either melatonin (10 mg/kg, intravenously), melatonin receptor antagonist
      luzindole (2.5 mg/kg, intravenously) plus melatonin (10 mg/kg, intravenously),
      luzindole alone (2.5 mg/kg, intravenously), or vehicle. MEASUREMENTS AND MAIN
      RESULTS: After 2 hrs of reperfusion, either liver function was assessed by plasma
      disappearance rate of indocyanine green or intravital microscopy of the liver was
      performed for evaluation of hepatic perfusion, hepatocellular redox state, and
      hepatic integrity. Compared with vehicle controls, melatonin therapy after
      hemorrhagic shock significantly improved plasma disappearance rate of indocyanine
      green, hepatic redox state, hepatocellular injury, and hepatic perfusion index.
      Coadministration of luzindole completely abolished the protective effect with
      respect to liver function only, and improvements regarding hepatic redox state,
      perfusion, and integrity were comparable with melatonin treatment alone.
      CONCLUSIONS: Melatonin therapy after hemorrhagic shock improves liver function,
      hepatic perfusion, redox state, and hepatic integrity. With respect to liver
      function, beneficial effects of the pineal hormone seem to be dependent on
      melatonin receptor activation.

PMID- 18090375
TI  - Antithrombin inhibits bronchoalveolar activation of coagulation and limits lung
      injury during Streptococcus pneumoniae pneumonia in rats.
AB  - OBJECTIVE: Alveolar fibrin deposition is a hallmark of pneumonia. It has been
      proposed that natural inhibitors of coagulation, including activated protein C,
      antithrombin, and tissue factor pathway inhibitor, exert lung-protective effects
      via anticoagulant and possibly anti-inflammatory pathways. We investigated the
      role of these natural anticoagulants in Streptococcus pneumoniae pneumonia.
      DESIGN: A controlled in vivo laboratory study. SETTING: Research laboratory of a
      university hospital. SUBJECTS: Total of 98 male Sprague-Dawley rats.
      INTERVENTIONS: Rats were challenged intratracheally with S. pneumoniae (serotype
      3, 10(6) colony forming units), inducing pneumonia. Rats were randomized to
      intravenous treatment with normal saline, activated protein C, antithrombin,
      tissue factor pathway inhibitor, heparin, or tissue-type plasminogen activator.
      MEASUREMENTS AND MAIN RESULTS: Rats infected with S. pneumoniae had increased
      thrombin-antithrombin complexes in bronchoalveolar lavage fluid, with decreased
      levels of antithrombin activity and fibrin degradation products. Administration
      of activated protein C, antithrombin, and tissue factor pathway inhibitor
      significantly limited these procoagulant changes. Furthermore, antithrombin
      treatment resulted in less bacterial outgrowth of S. pneumoniae and less
      histopathologic damage in lungs. CONCLUSIONS: Anticoagulant treatment attenuates
      pulmonary coagulopathy during S. pneumoniae pneumonia. Antithrombin seems to
      exert significant lung-protective effects in pneumococcal pneumonia in rats.

PMID- 18090376
TI  - Clinicians' evaluation and management of mental health, substance abuse, and
      chronic pain conditions in the intensive care unit.
AB  - OBJECTIVE: The purpose of this study was to describe clinicians' evaluation and
      management of co-existing mental health, substance abuse (MHSA), and chronic pain
      (CP) conditions in patients with prolonged critical illness. Little is known
      about the evaluation and management of these conditions in the intensive care
      unit, and practice guidelines do not address management in the context of
      critical illness, optimal sedation/analgesia, or ventilator weaning. DESIGN:
      Longitudinal qualitative description. SETTING: Intensive care unit of an urban
      academic medical center. PATIENTS: Total of 12 patients with co-existing MHSA or
      CP conditions who were weaning from mechanical ventilation. INTERVENTIONS:
      Intensive care unit clinicians, patients, and family members were formally
      interviewed and directly observed in the critical care setting for 56 consecutive
      weeks. MEASUREMENTS AND MAIN RESULTS: Transcribed interviews, field notes, and
      clinical records, representing >400 documents, were reviewed and coded using
      constant comparative analysis to identify the facilitators, barriers, contextual
      factors, and consequences associated with the evaluation and management of MHSA
      and CP conditions. Numeric clinical data supplemented and clarified thematic
      findings. Facilitators of MHSA and CP evaluation and management included family
      as history keepers, the use of subspecialty consultations, and anticipated
      alcohol withdrawal. Barriers included limited history taking and assessment of
      MHSA and CP conditions and the use of cognitive shortcuts. Consequences included
      nonintegration of MHSA and CP medications and diagnoses, episodic pharmacologic
      responses to psychobehavioral symptoms, and clinician-patient interpersonal
      tension. Contextual factors involved ambiguous psychobehavioral symptomatology,
      patients' critical illness and inability to speak, and competing clinical goals.
      CONCLUSIONS: The explicit evaluation and management of MHSA and CP conditions was
      highly variable and inconsistent across cases. Findings suggest that MHSA and CP
      conditions require monitoring and management similar to that required for other
      chronic conditions. Multidisciplinary, individual-level, and system-level
      responses are warranted to address the complex interplay of barriers,
      consequences, and context.

PMID- 18090377
TI  - Incidence and prediction of psychiatric morbidity after a motor vehicle accident
      in Japan: the Tachikawa Cohort of Motor Vehicle Accident Study.
AB  - OBJECTIVES: To assess both the incidence of new-onset psychiatric illness after
      involvement in a motor vehicle accident in Japan for comparison with Western data
      and the predictors of psychiatric morbidity and posttraumatic stress disorder
      (PTSD) evaluated immediately after the accident. DESIGN: Prospective cohort study
      of injured patients assessed immediately and 4-6 wks after involvement in a motor
      vehicle accident. SETTING: Intensive care unit in a teaching hospital in Tokyo,
      Japan. PATIENTS: Total of 100 consecutive patients with motor vehicle accident
      related injuries (mean Injury Severity Score, 11.2; mean Glasgow Coma Scale,
      14.5; age, 18-69 yrs) admitted to the intensive care unit. Patients with
      traumatic brain injury, suicidality, current psychiatric or neurologic illness,
      or cognitive impairment were excluded. MEASUREMENTS: An extensive clinical
      interview and evaluation of vital signs, sociodemographic variables, previous
      traumatic events, family history of psychopathology, Impact of Event Scale
      Revised, Hospital Anxiety and Depression Scale, Clinician-Administered PTSD
      Scale, and Mini-International Neuropsychiatric Interview. RESULTS: A total of 31
      patients showed some form of new-onset psychiatric illness at the 4- to 6-wk
      follow-up. The majority of illnesses consisted of depression (major depression, n
      = 16; minor depression, n = 7) and PTSD (full PTSD, n = 8; partial PTSD, n = 16).
      Other illnesses included alcohol dependence (n = 3), obsessive-compulsive
      disorder (n = 2), agoraphobia (n = 2), and social phobia (n = 1). Both
      psychiatric morbidity and PTSD were predicted by a sense of life threat (odds
      ratio, 4.2 and 6.2, respectively), elevated heart rate (odds ratio, 1.6 and 1.7),
      and higher Impact of Event Scale-Revised intrusion subscale score (odds ratio,
      1.1 and 1.1). CONCLUSION: This study showed that psychopathology and PTSD after a
      motor vehicle accident in Japan is common and that the incidence is within the
      range of that in Western countries. A combination of a sense of life threat,
      heart rate, and Impact of Event Scale-Revised intrusion subscale allowed for
      significant prediction of psychiatric morbidity and PTSD.

PMID- 18090381
TI  - Effect of hypertonic saline concentration on cerebral and visceral organ water in
      an uninjured rodent model.
AB  - OBJECTIVE: Hypertonic saline has been shown to be an effective osmotic agent to
      reduce brain water and hence brain volume and intracranial pressure. A direct
      correlation between dose and effect has been demonstrated, but no studies have
      compared the effects of different concentrations of the same osmotic load of
      hypertonic saline over time. We compared the effects of different tonicity of
      infused hypertonic saline on cerebral, lung, and small bowel water extraction
      over time under controlled conditions. DESIGN: Laboratory study. SETTING: Medical
      school. SUBJECTS: Male Wistar rats (280-450 g). INTERVENTIONS: Anesthetized rats
      were randomized to a 15-min intravenous bolus infusion of 0.9% NaCl or five
      equisodium but different concentrations of hypertonic saline: 4.2%, 7.5%, 10%,
      23.4%, and 30%. Following infusion, animals remained anesthetized for 60, 180, or
      300 mins without additional fluids given (n > or = 6 per group). Blood was
      sampled, total urine output was measured, and the animal was then killed under
      deep anesthesia. Cerebral, lung, and small bowel water contents were derived by
      wet/dry weight measures. MEASUREMENTS AND MAIN RESULTS: After 60 mins, hypertonic
      saline administered at 50 mosm/kg resulted in an increase in serum osmolarity in
      all hypertonic saline groups (p < .05 vs. normal saline), with a significantly
      greater increase measured using 23.4% or 30% hypertonic saline (23.4%, 365.0 +/-
      8.8 mosm/L, p < .05 vs. other lesser hypertonic saline doses). The durable effect
      was present throughout the 300-min period by all but the lowest hypertonic saline
      (4.2% NaCl). Lung but not small bowel organ water was diminished by hypertonic
      saline. Brain water content (79.1 +/- 0.2% in normal saline controls) was,
      however, significantly reduced. CONCLUSIONS: Hypertonic saline is effective in
      reducing organ water content in a setting of preserved blood-brain barrier but is
      not as effective in visceral organs. At equiosmotic doses of hypertonic saline,
      concentration plays no substantial role in altering serum osmolarity but appears
      to benefit duration of action. At very high concentrations, such as 23.4% NaCl,
      additional water extraction is also manifested. At such high concentration of
      NaCl, tonicity, indeed, matters, especially in water shifts across the blood
      brain barrier.

PMID- 18090383
TI  - Mortality and length-of-stay outcomes, 1993-2003, in the binational Australian
      and New Zealand intensive care adult patient database.
AB  - OBJECTIVE: Intensive care unit (ICU) outcomes have been the subject of
      controversy. The objective was to model hospital mortality and ICU length-of-stay
      time-change of patients recorded in the Australian and New Zealand Intensive Care
      Society adult patient database. DESIGN: Retrospective, cohort study of
      prospectively collected data on index patient admissions. SETTING: Australian and
      New Zealand ICUs, 1993-2003. PATIENTS: The Australian and New Zealand Intensive
      Care Society adult patient database, which contains data for 223,129 patients.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hospital mortality and ICU
      length of stay were modeled using logistic and linear regression, respectively,
      with determination (80%) and validation (20%) data sets. Model adequacy was
      assessed by discrimination (receiver operating characteristic curve area, AZ) and
      calibration (Hosmer-Lemeshow C) for mortality and R2 for length of stay.
      Predictor variables included patient demographics, severity score, surgical and
      ventilation status, ICU categories, and geographical locality. The data set
      comprised 223,129 patients: Their mean (SD) age was 59.2 (18.9) yrs, 41.7% were
      female, their mean (SD) Acute Physiology and Chronic Health Evaluation (APACHE)
      III score was 53 (31), they had 16.1% overall mortality rate, and 45.7% were
      mechanically ventilated. ICU length of stay was 3.6 (5.6) days. A(Z), C
      statistic, and R2 for developmental and validation model data sets were 0.88,
      17.64 (p = .02), and 0.18; and 0.88, 12.32 (p = .26), and 0.18, respectively.
      Variables with mortality impact (p < or = .001) were age (odds ratio [OR] 1.023),
      gender (OR 1.16; males vs. females), APACHE III score (OR 1.06), mechanical
      ventilation (OR 1.66), and surgical status (elective, OR 0.17; emergency, OR
      0.47; compared with nonsurgical). ICU level and locality had significant
      mortality-time effects. Similar variables were found to predict length of stay.
      Risk-adjusted mortality declined, during 1993-2003, from 0.19 (95% confidence
      interval 0.17-0.21) to 0.15 (0.13-0.16) and similarly for ventilated patients:
      0.26 (0.24-0.29) to 0.23 (0.21-0.25). Predicted mean ICU length of stay (days)
      demonstrated minimal overall time-change: 3.4 (2.2) in 1993 to 3.5 (2.7) in 2003,
      peaking at 3.7 (2.4) in 2000. CONCLUSIONS: Overall hospital mortality rate in
      patients admitted to Australian and New Zealand ICUs decreased 4% over 11 yrs. A
      similar trend occurred for mechanically ventilated patients. Length of stay
      changed minimally over this period.

PMID- 18090386
TI  - Antiretroviral drugs and liver injury.

PMID- 18090387
TI  - Undetectable hepatitis C virus RNA at week 4 as predictor of sustained
      virological response in HIV patients with chronic hepatitis C.
AB  - BACKGROUND: Low baseline serum hepatitis C virus (HCV)-RNA and clearance of
      viraemia at week 4 with pegylated interferon (pegIFN) plus ribavirin therapy
      predict sustained virological response (SVR) and enable a shorter duration of
      therapy in patients with chronic hepatitis C. It is unclear whether this applies
      to HIV/HCV-co-infected patients. PATIENTS AND METHODS: In the Peginterferon
      Ribavirin ESpana COinfection (PRESCO) trial, 389 co-infected patients received
      pegIFN-alpha2a 180 microg/week plus ribavirin 1000-1200 mg/day. Patients with HCV
      2/3 were treated for 6 or 12 months, whereas patients with HCV-1/4 were treated
      for 12 or 18 months. For each genotype, baseline HCV-RNA and rapid virological
      response (RVR), defined as under 50 IU/ml HCV-RNA at week 4, were evaluated as
      predictors of SVR in an 'on-treatment' analysis. RESULTS: Overall, SVR was
      achieved by 193 patients (49.6%), 68/191 (35.6%) with genotype 1, 110/152 (72.4%)
      with genotypes 2/3 and 15/46 (32.6%) with genotype 4. RVR was the best predictor
      of SVR regardless of HCV genotype. Only for HCV-1 patients, baseline HCV-RNA less
      than 500 000 IU/ml was also associated with SVR. In HCV-3 patients RVR had a
      positive predictive value (PPV) for SVR of 90%, with treatment for 24 or 48
      weeks. The PPV of SVR for patients with RVR was 69% for HCV-1 and 83% for HCV-4.
      CONCLUSION: Undetectable HCV-RNA at week 4 is the best predictor of curing
      chronic hepatitis C in HCV/HIV-co-infected patients. In HCV-1 patients, baseline
      HCV-RNA also predicts response. HIV patients with HCV-3 and RVR may permit
      shortening therapy duration to only 24 weeks of pegIFN plus 1000-1200 mg
      ribavirin.

PMID- 18090389
TI  - An unanticipated lack of consensus cytotoxic T lymphocyte epitopes in HIV-1
      databases: the contribution of prediction programs.
AB  - BACKGROUND: Most consensus HIV-1-specific cytotoxic T lymphocytes epitopes
      presented via intensively studied HLA molecules are thought to be known
      OBJECTIVE: To identify possible novel HIV-1 epitopes for HLA-B27 and HLA-B57; two
      HLA types which are abundantly studied because of their correlation with slow HIV
      disease progression. METHODS: HIV-1 consensus subtype B sequences were analysed
      using peptide prediction programs based on major histocompatibility complex
      binding, proteasomal cleavage and TAP (transporter associated with antigen
      processing) transport. Recognition of the novel identified epitopes by cytotoxic
      T lymphocytes was tested using interferon-gamma ELISpot assay. RESULTS: In total,
      22 novel epitopes predicted to be presented by either HLA-B27 or HLA-B57 were
      selected. Of these, 86% elicited significant immune responses in HIV-1-infected
      individuals. CONCLUSIONS: These data show that numerous HIV-1 epitopes remain to
      be identified, and that prediction programs are powerful tools for this purpose.

PMID- 18090388
TI  - HIV-1 escape to CCR5 coreceptor antagonism through selection of CXCR4-using
      variants in vitro.
AB  - BACKGROUND: HIV-1 coreceptor switch from CCR5 to CXCR4 is associated with disease
      progression and AIDS. Selection of resistant HIV-1 to CCR5 agents in cell culture
      has often occurred in the absence of coreceptor switch. With CCR5 antagonists
      currently in clinical trials, their impact on coreceptor use is still in doubt.
      METHODS: Six R5 HIV-1 strains were passaged in lymphoid cells expressing high
      CXCR4 and low CCR5, in the absence or presence of CCR5 inhibitors (TAK-779, mAb
      2D7 and CCL5). AMD3100, zidovudine and lamivudine were used as controls.
      Phenotype and genotype changes as well as virus coreceptor use were evaluated.
      RESULTS: In the absence of drug pressure, three out of six strains expanded their
      coreceptor use to CXCR4 at different times, suggesting that not all virus strains
      had the capacity to do so. Lowering the replication rate with a suboptimal
      concentration of different anti-HIV agents (reverse transcriptase inhibitors or
      CCR5 agents) delayed coreceptor switch. However, virus breakthrough was observed
      earlier in the presence of CCR5-targeting agents than in presence of reverse
      transcriptase inhibitors and was associated with a change in sensitivity to TAK
      779 or AMD3100, virus coreceptor expansion to CXCR4 and changes in the V3 loop
      region of gp120. CONCLUSION: Our results suggest that HIV-1 may escape CCR5 drug
      pressure through coreceptor switch. Experimental conditions strongly determine
      the outcome of CCR5 drug pressure in cell culture. A cell culture model of the
      evolution of HIV-1 coreceptor use may be relevant to assess the propensity of
      clinical isolates to develop resistance through coreceptor change.

PMID- 18090390
TI  - IL-27, a novel anti-HIV cytokine, activates multiple interferon-inducible genes
      in macrophages.
AB  - OBJECTIVE: IL-27 is a novel anti-HIV cytokine that inhibits HIV-1 replication in
      both CD4 T cells and monocyte-derived macrophages (MDM) as IFN-alpha does. To
      elucidate the mechanism of the antiviral activity, we compared the activity and
      the gene expression profile of IL-27-treated cells with that of IFN-alpha-treated
      cells. METHODS: CD4 T cells and monocytes were isolated from peripheral blood
      mononuclear cells of healthy donors. CD4 T cells were stimulated with
      phytohemagglutinin, and MDM were induced from monocytes using macrophage-colony
      stimulating factor. HIV-1 replication was monitored by p24 antigen capture assay.
      The gene expression profiles were analysed using DNA microarray analysis. The
      increase in the expression of IFN-inducible genes (IFIG) was confirmed by the
      Quantigene plex assay. RESULTS: Both cytokines preferentially inhibited HIV-1
      replication in MDM compared with CD4 T cells. Quantitative real time polymerase
      chain reaction, enzyme-linked immunosorbent assay and neutralization assay using
      anti-IFN indicated that IFN-alpha, IFN-beta and IFN-gamma had no significant
      impact on IL-27-mediated HIV inhibition. DNA microarray analysis illustrated that
      IFN-alpha induced 33 and 18 IFIG in MDM and CD4 T cells, respectively. IL-27
      induced 28 IFIG in MDM and five IFIG in CD4 T cells. The quantitative assay
      confirmed that IL-27 activated genes of RNA-dependent kinase, oligoadenylate
      synthetase, myxovirus protein, and apolipoprotein B messenger RNA-editing enzyme
      catalytic polypeptide-like 3G. CONCLUSION: IL-27 differentially regulates the
      gene expression between CD4 T cells and MDM. IL-27 significantly induces
      antiviral genes in MDM as does IFN-alpha, suggesting that IL-27 inhibits HIV
      replication in MDM via mechanism(s) similar to that of IFN-alpha.

PMID- 18090391
TI  - The role of antiretroviral therapy in the incidence of pancreatitis in HIV
      positive individuals in the EuroSIDA study.
AB  - AIM: This study investigated the incidence of pancreatitis and its association
      with antiretroviral therapy (ART), focussing on stavudine and didanosine.
      METHODS: EuroSIDA has collected information on pancreatitis since Summer 2001.
      All identified cases have been verified by the coordinating centre. Individuals
      were followed from June 2001 or the date of entry into EuroSIDA (whichever
      occurred later) until a diagnosis of pancreatitis or the last study visit.
      Factors associated with pancreatitis were investigated using Poisson regression.
      Cumulative lengths of exposure to didanosine without stavudine, stavudine without
      didanosine, stavudine with didanosine, and other ART were time-updated variables.
      Treatment variables were fitted with a 6-month time lag. RESULTS: There were 43
      (nine presumptive) pancreatic events in 9678 individuals during 33 742 person
      years (incidence 1.27/1000 person-years). The incidence among those with no, 2 or
      less and over 2 years' exposure to ART including stavudine and didanosine was
      1.24, 1.73 and 0.78/1000 person-years, respectively. In multivariable analysis,
      higher baseline CD4 cell counts were associated with a decreased risk of
      pancreatitis. There was no evidence of an association of pancreatitis with
      cumulative exposure to didanosine and stavudine, didanosine without stavudine,
      stavudine without didanosine, or other ART. CONCLUSION: We observed a low overall
      rate of pancreatitis in the years 2001-2006, and did not find an association of
      an increased incidence of pancreatitis with cumulative exposure to antiretroviral
      agents generally, and to didanosine and stavudine in particular.

PMID- 18090392
TI  - HIV-1-infected CD8+CD4+ T cells decay in vivo at a similar rate to infected CD4 T
      cells during HAART.
AB  - OBJECTIVES: To investigate the potential for CD4+CD8+ T cells [CD8 double
      positive (CD8 DP)] T cells to form a reservoir of HIV-1 following HAART through
      measurement of the rate of decay of infected CD4/CD8 DP T cells. METHODS: HIV-1
      proviral loads in highly pure CD4 and CD8 DP T cells were determined for study
      subjects before and after 200-400 days of therapy and HIV-1 DNA decay rates were
      calculated. RESULTS: Before therapy, HIV-1 proviral load in CD8 DP correlated
      negatively with CD4 cell count. Decay rates of HIV-1-infected CD4 and CD8 DP T
      cells were similar. Rates for CD8 DP T cells correlated with the time to
      suppression of viral replication, whereas no such relationship was true for CD4
      cell decay rates. A significant reduction in activated cells was observed for
      both cell types. The action of HAART on HIV-1 replication was similar for both
      CD4 cells and CD8 DP T cells, although the rate of clearance of infected CD8 DP T
      cells appeared more critical for a rapid reduction in plasma viral load. Although
      the size of the CD8 DP T cell reservoir in peripheral blood was smaller relative
      to that of CD4 cells, HAART did not completely clear HIV-1 infection from this
      cell subset. CONCLUSION: This study confirmed that CD8 DP T cells are a major
      reservoir for HIV-1 in vivo and, therefore, represent a potential reservoir for
      HIV-1 during HAART, in a manner analogous to that of CD4 T cells.

PMID- 18090393
TI  - Antiretroviral therapy using zidovudine, lamivudine, and efavirenz in South
      Africa: tolerability and clinical events.
AB  - OBJECTIVE: To describe the safety and tolerability of zidovudine, lamivudine, and
      efavirenz in a low-income setting. DESIGN: We conducted a prospective cohort
      study in a workplace HAART programme in South Africa, which uses a first-line
      regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical
      and laboratory monitoring 6-monthly pre-HAART and at 2, 6, 12, 24, 36, 48 weeks
      during HAART. METHODS: We assessed the incidence of specified clinical and
      laboratory events (AIDS Clinical Trials Group grade 3 or higher) and associated
      regimen changes, hospitalizations, and deaths one year before HAART initiation
      and one year on-HAART using person-year analysis. RESULTS: Between November 2002
      and October 2005, 853 subjects (98% male, median age 40 years, and median CD4
      cell count at HAART initiation 186 cells/mul) met enrollment criteria. The
      incidence of events on-HAART was higher than pre-HAART for neutropenia and
      nausea/vomiting. Dizziness was common early after HAART initiation (not evaluated
      pre-HAART). Of those with neutropenia, 88% had no apparent clinical consequences.
      The incidence of anemia, hepatotoxicity, peripheral neuropathy, and rash was
      similar or higher pre-HAART than on-HAART. Mean hemoglobin rose during the time
      on-HAART and was higher at 24 and 48 weeks than at baseline (P < 0.001).
      DISCUSSION: This regimen was well tolerated with a short-term increase in
      neutropenia, nausea, and probably neurocerebellar events. Most significantly, in
      contrast to reports from high-income countries, we observed a long-term
      improvement in the hemoglobin concentration.

PMID- 18090394
TI  - Differential adherence to combination antiretroviral therapy is associated with
      virological failure with resistance.
AB  - OBJECTIVES: To investigate the occurrence of differential adherence to components
      of combination antiretroviral therapy and assess its predictors and association
      with virological failure and antiretroviral medication resistance. DESIGN: A
      secondary analysis of prospective clinical trial data. METHODS: The Flexible
      Initial Retrovirus Suppressive Therapies study (Community Programs for Clinical
      Research on AIDS 058) was a randomized trial comparing non-nucleoside reverse
      transcriptase inhibitor (NNRTI) versus protease inhibitor (PI) versus NNRTI plus
      PI-based (three-class) antiretroviral therapy in treatment-naive HIV-1-infected
      individuals. Adherence was assessed at months 1 and 4, and then every 4 months.
      Differential adherence, defined as any difference in self-reported level of
      adherence to individual antiretroviral medications at the same timepoint, was
      evaluated as a binary time-updated variable in multivariate Cox regression
      analyses of time to initial virological failure (HIV-RNA > 1000 copies/ml) and
      initial virological failure with genotypic antiretroviral resistance. RESULTS:
      Differential adherence was reported at least once by 403 of 1379 participants
      (29%), over 60 months median follow-up. Differential adherence was more commonly
      reported by participants randomly assigned to the three-class strategy (35%) than
      the NNRTI (28%) or PI (25%) strategies (P = 0.005), but was not associated with
      demographic or baseline disease-specific factors. Of those reporting differential
      adherence, 146 (36%) reported it before initial virological failure. These
      participants had an increased risk of initial virological failure and initial
      virological failure with antiretroviral resistance compared with participants
      without differential adherence before initial virological failure. CONCLUSION:
      Differential adherence was commonly reported and was associated with an increased
      risk of initial virological failure and initial virological failure with
      antiretroviral resistance.

PMID- 18090395
TI  - Prevention of mother-to-child transmission: program changes and the effect on
      uptake of the HIVNET 012 regimen in Malawi.
AB  - OBJECTIVE(S): To evaluate uptake of HIV testing in a prevention of mother-to
      child transmission program (PMTCT) in Lilongwe, Malawi from April 2002 until
      December 2006. DESIGN: Retrospective analysis of monthly reports from the
      beginning of the program. SETTING: Four antenatal clinics in Lilongwe, Malawi.
      METHODS: Pregnant women attending urban antenatal clinics in Lilongwe were
      invited to participate in a PMTCT program. Women were given information and
      education on antenatal care and PMTCT in groups of 8 to 12. Written informed
      consent for HIV testing was obtained privately. Women returned for the test
      result 1-2 weeks later. Mothers and infants were given the HIVNET 012 regimen.
      Rapid HIV testing and 'opt-out' testing were instituted in July 2003 and April
      2005, respectively. Infants were tested using HIV DNA PCR and, if HIV positive, a
      CD4 cell percentage was obtained and the infants were referred for further
      medical evaluation and treatment. RESULTS: The program reached 20 000 pregnant
      women in the first 12 months. Acceptance of HIV testing increased from 45% to 73%
      (P < 0.001) when rapid, same day testing was instituted. When opt-out testing was
      instituted, 99% of the mothers agreed to testing. Of the infants tested, 15.5%
      were HIV positive. CONCLUSION: Rapid HIV testing using the opt-out method
      increased acceptance of HIV testing in the PMTCT program to 99% in urban
      Lilongwe, Malawi.

PMID- 18090396
TI  - Survival following HIV infection of a cohort followed up from seroconversion in
      the UK.
AB  - OBJECTIVES: To estimate changes over calendar time in survival following HIV
      seroconversion in the era of HAART and to provide updated survival estimates.
      METHODS: Using data from a UK cohort of persons with well estimated dates of HIV
      seroconversion, we analysed time from seroconversion to death from any cause
      using Cox models, adjusted for prognostic factors. Kaplan-Meier methods were then
      used to determine the expected survival in each calendar period. RESULTS: 2275
      seroconverters were included with 18 695 person-years of follow up. A total of
      444 (20%) died. The relative risk of death, compared with pre-1996, decreased
      over time to 0.63 [95% confidence interval (CI), 0.48-0.81], 0.24 (0.17-0.34),
      0.14 (0.10-0.21), 0.08 (0.05-0.13) and 0.03 (0.02-0.06) in 1996-1997, 1998-1999,
      2000-2001, 2002-2003 and 2004-2006, respectively. An elevated risk of death was
      associated with older age at seroconversion [hazard ratio (HR), 1.49; 95% CI,
      1.34-1.66 per 10-year increase] and HIV infection through injecting drug use (HR,
      1.53; 95% CI, 1.17-2.00). In 2000-2006, the proportion of individuals expected to
      survive 5, 10 and 15 years following seroconversion was 99%, 94% and 89%,
      respectively. CONCLUSIONS: Survival following HIV seroconversion has continued to
      improve over calendar time in our cohort, even in the more recent years of HAART
      availability. HIV seroconverters, by definition identified early in their
      infection, are likely to have the greatest opportunity for intervention; if
      similar high survival expectations are to be seen in the wider HIV-infected
      population, early diagnosis is likely to be crucial.

PMID- 18090397
TI  - Markers for predicting mortality in untreated HIV-infected children in resource
      limited settings: a meta-analysis.
AB  - OBJECTIVES: To evaluate the prognostic value of selected laboratory and growth
      markers on the short-term risk of mortality in untreated HIV-infected children in
      resource-limited settings. DESIGN: A meta-analysis of individual longitudinal
      data on children aged 12 months onwards from 10 studies (nine African, one
      Brazilian in the 3Cs4kids collaboration). METHODS: The risk of death within 12
      months based on age and the most recent measurements of laboratory and growth
      markers was estimated using Poisson regression models, adjusted for cotrimoxazole
      prophylaxis use and study effects. RESULTS: A total of 2510 children contributed
      357 deaths during 3769 child-years-at-risk, with 81% follow-up occurring after
      start of cotrimoxazole. At first measurement, median age was 4.0 years
      (interquartile range, 2.2-7.0 years), median CD4% was 15% and weight-for-age z
      score -1.9. CD4% and CD4 cell count were the strongest predictors of mortality,
      followed by weight-for-age and haemoglobin. After adjusting for these markers,
      the effects of total lymphocyte count and BMI-for-age were relatively small.
      Young children who were both severely malnourished and anaemic had high mortality
      regardless of CD4 values, particularly those aged 1-2 years. By contrast, high
      CD4% or CD4 cell count values predicted low mortality level amongst either
      children older than 5 years or those younger with neither severe malnutrition nor
      anaemia. CONCLUSIONS: CD4 measurements are the most important indicator of
      mortality and wider access to affordable tests is needed in resource-limited
      settings. Evaluation of antiretroviral initiation in children also needs to
      consider weight-for-age and haemoglobin. Prevention and treatment of malnutrition
      and anaemia is integral to HIV paediatric care and could improve survival.

PMID- 18090398
TI  - 'Time is costly': modelling the macroeconomic impact of scaling-up antiretroviral
      treatment in sub-Saharan Africa.
AB  - BACKGROUND: Macroeconomic policy requirements may limit the capacity of national
      and international policy-makers to allocate sufficient resources for scaling-up
      access to HIV care and treatment in developing countries. METHOD: An endogenous
      growth model, which takes into account the evolution of society's human capital,
      was used to assess the macroeconomic impact of policies aimed at scaling-up
      access to HIV/AIDS treatment in six African countries (Angola, Benin, Cameroon,
      Central African Republic, Ivory Coast and Zimbabwe). RESULTS: The model results
      showed that scaling-up access to treatment in the affected population would limit
      gross domestic product losses due to AIDS although differently from country to
      country. In our simulated scenarios of access to antiretroviral therapy, only
      10.3% of the AIDS shock is counterbalanced in Zimbabwe, against 85.2% in Angola
      and even 100.0% in Benin (a total recovery). For four out of the six countries
      (Angola, Benin, Cameroon, Ivory Coast), the macro-economic gains of scaling-up
      would become potentially superior to its associated costs in 2010. CONCLUSION:
      Despite the variability of HIV prevalence rates between countries, macro-economic
      estimates strongly suggest that a massive investment in scaling-up access to HIV
      treatment may efficiently counteract the detrimental long-term impact of the HIV
      pandemic on economic growth, to the extent that the AIDS shock has not already
      driven the economy beyond an irreversible 'no-development epidemiological trap'.

PMID- 18090399
TI  - Missed opportunities for earlier HIV diagnosis within primary and secondary
      healthcare settings in the UK.
AB  - OBJECTIVE: To identify opportunities for earlier HIV diagnosis within primary and
      secondary care settings in the UK in Africans with newly diagnosed HIV infection.
      METHODS: A survey of newly diagnosed HIV-positive Africans attending 15 HIV
      treatment centres across London was conducted between April 2004 and February
      2006. The survey consisted of a confidential self-completed questionnaire linked
      to clinician-completed clinical records. RESULTS: A total of 263 questionnaires
      were completed, representing an uptake rate of 79.5% of patients approached and
      49.8% (131/263) of participants presented with advanced HIV disease (CD4 cell
      count < 200 cells/mul at diagnosis). In the year prior to HIV diagnosis 76.4%
      (181/237) had seen their GP, 38.3% (98/256) had attended outpatient services, and
      15.2% (39/257) inpatient services, representing missed opportunities for earlier
      HIV diagnosis. Of those attending GP services the issue of HIV and/or HIV testing
      was raised for 17.6% (31/176) and 37.1% (78/210) had a previous negative HIV
      test, 32.5% of these within the UK. Medical attention was sought for wide ranging
      reasons, often not obviously connected to underlying HIV status. Despite the
      population predominantly coming from countries of high HIV prevalence personal
      appreciation of risk was comparatively low and knowledge of benefits of testing
      lacking. CONCLUSION: Africans are accessing health services but clinicians are
      failing to use these opportunities effectively for preventive and diagnostic
      purposes with regards to HIV infection. Comparatively low appreciation of
      personal risk and lack of perceived ill health within this community means
      clinicians need to be more proactive in addressing HIV.

PMID- 18090400
TI  - Spatial distribution of HIV prevalence and incidence among injection drugs users
      in St Petersburg: implications for HIV transmission.
AB  - INTRODUCTION: The HIV/AIDS epidemic in St Petersburg, as in much of Russia, is
      concentrated among injection drug users (IDU) in whom prevalence reached 30% in
      2003. Understanding the dynamics of the epidemic is important in developing
      appropriate responses in the resource-constrained context of Russian cities such
      as St Petersburg. METHODS: IDU were contacted and screened to create a
      seronegative cohort for prevention and vaccine studies. At screening, individuals
      provided sociodemographic, drug use, and injection and sex-related risk behavior
      data. Seronegative individuals who enrolled in the cohort were followed for one
      year and tested for HIV semiannually. Residential addresses were entered into a
      geographical information system programme and analysed for spatial clustering
      using Moran's I and nearest-neighbor analysis. RESULTS: We mapped 788 of the 900
      study participants to discrete locations within St Petersburg; 236 (29.9%) were
      HIV seropositive at baseline. Although there was no clustering of the study
      population as a whole, HIV-infected individuals were tightly clustered and
      prevalence co-clustered with high frequency of heroin injection, receptive
      syringe sharing, being younger than 24 years, and living with parents. These
      clusters were restricted to 5% of populated areas of the city. We mapped 18 of 20
      incident cases detected among the cohort, and more than half were located within
      or adjacent to the clusters. INTERPRETATION: Spatial analysis identified linkages
      between disease prevalence and risky injection behaviors that were not evident
      using traditional epidemiological analysis. The analysis also identified where
      resources might be allocated geographically for maximum impact in slowing the HIV
      epidemic among IDU.

PMID- 18090401
TI  - Reduced rates of HIV acquisition during unprotected sex by Kenyan female sex
      workers predating population declines in HIV prevalence.
AB  - OBJECTIVES: Female sex workers (FSWs) form a core group at high risk of both
      sexual HIV acquisition and secondary transmission. The magnitude of these risks
      may vary by sexual risk taking, partner HIV prevalence, host immune factors and
      genital co-infections. We examined temporal trends in HIV prevalence and per-act
      incidence, adjusted for behavioral and other variables, in FSWs from Nairobi,
      Kenya. METHODS: An open cohort of FSWs followed since 1985. Behavioral and
      clinical data were collected six monthly from 1985 to 2005, and sexually
      transmitted infection (STI) diagnostics and HIV serology performed. A Cox
      proportional hazards model with time-dependent covariables was used to estimate
      infection risk as a function of calendar time. RESULTS: HIV prevalence in new FSW
      enrollees peaked at 81% in 1986, and was consistently below 50% after 1997.
      Initially uninfected FSWs remained at high risk of acquiring HIV throughout the
      study period, but the rate of HIV acquisition during unprotected sex with a
      casual client declined by over four-fold. This reduction correlated closely with
      decreases in gonorrhea prevalence, and predated reductions in the Kenyan HIV
      population prevalence by over a decade. CONCLUSIONS: The per-act rate of HIV
      acquisition in high-risk Nairobi FSWs fell dramatically between 1985 and 2005.
      This decline may represent the impact of improved STI prevention/therapy,
      immunogenetic shifts in at-risk women, or changes in the proportion of HIV
      exposures occurring with clients who had acute HIV infection. Declining HIV
      incidence in high-risk cohorts may predict and/or be causally related to future
      reductions in population prevalence.

PMID- 18090402
TI  - High HIV incidence in a community with high HIV prevalence in rural South Africa:
      findings from a prospective population-based study.
AB  - OBJECTIVES: To measure HIV incidence in a rural area of South Africa with high
      HIV prevalence and to analyze risk factors for acquisition of HIV using a
      prospective population-based cohort study. METHODS: Data from two rounds (2003
      2005) of a large prospective population-based HIV survey in rural KwaZulu-Natal
      were used to calculate HIV incidence by sex and 5-year age group. Multiple
      imputations (MI) were used to adjust for selection effects and risk factors for
      acquiring HIV were examined in Weibull multiple regression. RESULTS: During 5253
      person-years at risk, 170 individuals became seropositive. The crude HIV
      incidence rate per 100 person-years was 3.8 [95% confidence interval (CI), 3.2
      4.6] in women aged 15-49 years and 2.3 (95% CI, 1.8-3.1) in men aged 15-54 years.
      MI significantly increased the HIV incidence rates both in women and men [7.9/100
      person-years (95% CI, 7.4-8.4) and 5.1/100 person-years (95% CI 4.1-6.2),
      respectively]. When holding other factors constant in Weibull multiple
      regression, the hazard of HIV seroconversion was approximately twice as high in
      people who were currently unmarried but had a partner than among people who were
      currently married (P < 0.001) and increased with increasing distance from a
      government health clinic (P = 0.051) and decreasing distance from a primary road
      (P = 0.002). CONCLUSION: In this high HIV prevalence community in rural South
      Africa HIV incidence is very high. The present focus on antiretroviral treatment
      needs to be balanced with a renewed emphasis on HIV prevention for both sexes.

PMID- 18090403
TI  - Incidence of pancreatitis in HIV-infected patients: comment on findings in
      EuroSIDA cohort.

PMID- 18090404
TI  - First phase I clinical trial of an HIV-1 subtype D gp140 envelope protein
      vaccine: immune activity induced in all study participants.
AB  - To combat HIV-1 diversity, we are developing a multienvelope vaccine (comprising
      DNA, vaccinia virus and protein vectors). Toward this goal, we conducted a phase
      I clinical trial of EnvPro, a gp140 protein formulated in alum. The vaccine was
      well tolerated and elicited an immune response in every trial participant.

PMID- 18090406
TI  - Short-term increase in unsafe sexual behaviour after initiation of HAART in Cote
      d'Ivoire.
AB  - A study of 312 untreated and 303 HAART-initiating patients to determine whether
      HAART is related to sexual risk taking in Cote d'Ivoire. At enrollment,
      unprotected sex was higher among untreated patients (P = 0.014). During follow
      up, risk taking was similar (P = 0.484) as a result of an increase in unprotected
      sex among treated patients (from 20.4 to 30.1%, P < 0.0001) and stability among
      untreated patients (from 27.0 to 28.8%, P = 0.301). HAART appeared to be
      associated with sexual risk taking.

PMID- 18090405
TI  - Interruptions of tenofovir/emtricitabine-based antiretroviral therapy in patients
      with HIV/hepatitis B virus co-infection.
AB  - Thai patients enrolled in STACCATO with HIV/hepatitis B virus (HBV) co-infection
      and tenofovir/emtricitabine-based antiretroviral therapy (ART) were randomly
      assigned to continuous treatment or CD4 cell count-guided interruptions. HBV
      replication was suppressed below detection in 15/16 patients. Structured
      treatment interruption increased transaminases and HBV viraemia in five of six
      patients; one flare was severe. Conversion to anti-hepatitis Be occurred with
      continuous treatment only. Tenofovir/emtricitabine-containing ART is highly
      effective in controlling chronic HIV/HBV co-infection but treatment should not be
      interrupted.

PMID- 18090407
TI  - Chronology of the HIV-1 CRF07_BC expansion in East Asia.
AB  - The HIV-1 epidemic among injecting drug users (IDU) in Taiwan is caused primarily
      by CRF07_BC infections. Evolutionary analyses, which utilize outgroup reference
      strains from northwestern China (Xinjiang), reveal that CRF07_BC was introduced
      into southern Taiwan in 1998-2001 and spread to central-northern Taiwan in 2001
      2003, causing the largest HIV/AIDS epidemic in Taiwan. The separate introduction
      of CRF07_BC into Xinjiang occurred in 1992-1995. This study illustrates the
      temporal dynamics of CRF07_BC spread among IDU across east Asia.

PMID- 18090408
TI  - Thymic 18F-fluorodeoxyglucose uptake on positron emission tomography scanning
      after doxorubicin, bleomycin, vincristin and dacarbazine chemotherapy and highly
      active antiretroviral therapy in HIV-associated Hodgkin's disease in an adult.

PMID- 18090409
TI  - Gingival ulcers as first manifestation of leishmaniasis and HIV infection.

PMID- 18090410
TI  - Why don't physicians test for HIV?

PMID- 18090412
TI  - Clinical interaction between efavirenz and phenytoin.

PMID- 18090413
TI  - Response to "key amprenavir resistance mutations counteract dramatic efficacy of
      darunavir in highly experienced patients".

PMID- 18090414
TI  - Mainstreaming HIV/AIDS program into infrastructure development and community
      preparedness.

PMID- 18090416
TI  - The uniqueness of Gogi aphasia owing to temporal lobar atrophy.
AB  - In Japan, a syndrome in which the semantic memory for words is impaired, in the
      presence of preserved phonological and syntactic aspects of language, is called
      Gogi (for the Japanese term meaning "word meaning") aphasia. In this brief
      historical report, Gogi aphasia is described and compared with the corresponding
      disorder called semantic dementia.

PMID- 18090417
TI  - Diagnostic criteria for the behavioral variant of frontotemporal dementia
      (bvFTD): current limitations and future directions.
AB  - The most widely established diagnostic criteria for the behavioral variant of
      frontotemporal dementia have now been in use for almost a decade. Although
      consensus criteria have provided a much needed standard for frontotemporal
      dementia research, a growing body of evidence suggests that revisions are needed
      to improve their applicability. In this article, we discuss the limitations of
      current diagnostic criteria and propose the establishment of an international
      consortium to revise diagnostic and research criteria for the behavioral variant
      of frontotemporal dementia.

PMID- 18090418
TI  - Frontotemporal dementia and semantic dementia: anatomic variations on the same
      disease or distinctive entities?
AB  - Research into the non-Alzheimer dementias has exploded over the last 2 decades,
      and frontotemporal lobar degeneration has emerged as the most common cause of
      dementia in patients below the age of 65. In 1998, an international consortium of
      investigators focusing on this disease entity met and agreed upon the
      classification of 3 subtypes of frontotemporal lobar degeneration, using regional
      atrophy to distinguish them. These are: a frontally predominant form called
      frontotemporal dementia, a temporally predominant form called semantic dementia,
      and a left-frontally predominant syndrome, called progressive nonfluent aphasia.
      With the rise of genetic and neuropathologic findings, however, the usefulness of
      this subtype classification has been called into question. This paper discusses
      the major pertinent findings, and the implications of classifying the disease on
      the basis of atrophy versus genetic or molecular mechanisms.

PMID- 18090419
TI  - Progressive nonfluent aphasia and its characteristic motor speech deficits.
AB  - Progressive nonfluent aphasia (PNFA) is a clinical syndrome characterized by
      motor speech impairment and agrammatism, with relative sparing of single word
      comprehension and semantic memory. PNFA has been associated with the
      characteristic pattern of left anterior insular and posterior frontal atrophy,
      including the motor and premotor regions and Broca's area. Postmortem
      histopathologic evidence has shown that PNFA is usually associated with tau
      pathology, although focal Alzheimer disease pathology and tau-negative, ubiquitin
      TDP-43 inclusions also have been reported in association with this clinical
      syndrome. We performed a detailed analysis of motor speech errors in 18 patients
      with PNFA and investigated their neural correlates using voxel-based morphometry
      on magnetic resonance imaging scans. Seven patients demonstrated only apraxia of
      speech (AOS) errors, whereas 11 showed AOS along with dysarthria. Slow rate of
      speech, effortful articulation with groping, and consonant distortions were the
      most common AOS errors. Hypernasality was the most represented dysarthric feature
      and dysarthria was most often classified as spastic, hypokinetic, or mixed
      spastic-hypokinetic. Neuroimaging results demonstrated that patients with AOS
      only and AOS plus dysarthria showed atrophy in the left posterior frontal,
      anterior insular, and basal ganglia regions when compared with controls. Patients
      with AOS plus dysarthria showed greater damage than patients with AOS-only in the
      left face portion of primary motor cortex and left caudate. PNFA is a distinct
      frontotemporal lobar degeneration clinical syndrome associated with
      characteristic clinical, neuroimaging, and pathologic features. The clinical
      features are driven by the severity of left frontal and caudate damage.

PMID- 18090420
TI  - Identification and characterization of frontal lobe degeneration: historical
      perspective on the development of FTD.
AB  - This is a historical account of the development of the concept frontotemporal
      dementia, beginning with our discovery in the late 60s of a simple degenerative
      form. It was named frontal lobe degeneration of non-Alzheimer type to clearly
      separate it from the then almost totally dominating diagnosis Alzheimer disease.
      In the absence of immunohistochemical methods for specific disease markers, we
      had to rely solely on structural features. Later, from the 80s, the successively
      introduced methods to show glial acidic protein, tau, synaptophysin, ubiquitin,
      and other markers confirmed our impression of a simple type of degeneration.
      These methods also added further forms with additional features, and from the 90s
      genetics has contributed new disease characteristics, all these advances leading
      up to the present conceptual structure of frontotemporal lobar degeneration.

PMID- 18090421
TI  - Links between frontotemporal lobar degeneration, corticobasal degeneration,
      progressive supranuclear palsy, and amyotrophic lateral sclerosis.
AB  - Frontotemporal lobar degeneration, corticobasal degeneration (CBD), progressive
      supranuclear palsy, and amyotrophic lateral sclerosis have been considered
      distinct clinicopathologic entities with few issues in common other than
      neurodegeneration being central to all. The aim of this paper is to highlight the
      clinical, topographic, pathologic, proteomic, and genetic similarities among
      these disorders and the syndromes through which each disorder is exhibited. The
      critical roles of tau and TAR DNA-binding protein 43 (TDP-43) dysfunction in the
      disorders and syndromes are emphasized. Although confusion certainly remains, and
      the ability to predict the underlying proteinopathy in the various
      neurodegenerative syndromes is far from perfect, there is optimism that insights
      gained over the next few years will enhance our ability to accurately identify
      the amyloidopathies, tauopathies, and TDP-43opathies early in the disease course,
      potentially improving the ability to impact these diseases once targeted
      therapies have been developed.

PMID- 18090422
TI  - Clinical features and survival of 3R and 4R tauopathies presenting as behavioral
      variant frontotemporal dementia.
AB  - We compared the clinical characteristics of 3 repeat (3R) and 4 repeat (4R) tau
      positive cases (tauopathies) presenting as behavior variant frontotemporal
      dementia (bv-FTD). We identified and retrospectively reviewed demographics and
      clinical features of patients with pathologically confirmed tau-positive
      frontotemporal lobar degeneration in a blinded fashion. Those presenting as bv
      FTD were divided according to their tau isoform, 3R versus 4R, and compared with
      age-matched and sex-matched control patients with 4R tauopathies but presenting
      clinical syndromes other than bv-FTD. Twenty-four cases with tau-positive bv-FTD
      and 18 4R tau-positive controls were included in the study. Patients with 4R
      tauopathies had significantly shorter disease duration than patients with 3R
      tauopathy (median, 6.5 y vs. 9.5 y; P<0.05), despite similar age of disease onset
      and regardless of whether bv-FTD was the presenting clinical syndrome. Among bv
      FTD cases, those with 4R tauopathies were more likely to display behavioral
      underactivity than those with 3R tauopathy (P=0.03), although 3R and 4R tauopathy
      patients shared many similar clinical features. In summary, survival in 4R
      tauopathies seemed independent of the presenting clinical phenotype, and there
      may be subtle clinical differences between bv-FTD patients with 3R and 4R
      tauopathies.

PMID- 18090423
TI  - The neuropathology of FTD associated With ALS.
AB  - There is increasing recognition of a clinical overlap between frontotemporal
      dementia (FTD) and amyotrophic lateral sclerosis (ALS). Recent advances in our
      understanding of the neuropathologic, biochemical, and genetic basis of these
      conditions provides evidence for a common underlying pathogenesis. The
      neuropathology in most cases of FTD with ALS is a subtype of frontotemporal lobar
      degeneration, characterized by neuronal inclusions that are immunoreactive for
      ubiquitin but not tau (frontotemporal lobar degeneration with ubiquitinated
      inclusions). These cases show significant pathologic overlap with clinically pure
      FTD and those with classic ALS. Moreover, the ubiquitinated pathologic protein in
      all these conditions has recently been identified as TDP-43. A number of families
      have been reported with autosomal dominant FTD-ALS linked to chromosome 9p and
      these also have TDP-43-positive frontotemporal lobar degeneration with
      ubiquitinated inclusions pathology. Together, these findings suggest that FTD-ALS
      is part of a clinicopathologic spectrum of disease, now identified as TDP-43
      proteinopathies.

PMID- 18090424
TI  - Pick complex--historical introduction.
AB  - This historical summary follows the major conceptual developments of the cohesive
      rather than the fractionated view of the disease, named after Pick. Clinical and
      biologic evidence in favor the entity is discussed. The changing and
      proliferating knowledge and terminology requires the integration of several
      levels of descriptions, while keeping the work in the past in sight. A historical
      perspective helps to prevent the chaos of terminological confusion and
      reinventing the wheel.

PMID- 18090425
TI  - Divergent social functioning in behavioral variant frontotemporal dementia and
      Alzheimer disease: reciprocal networks and neuronal evolution.
AB  - Behavioral variant frontotemporal dementia (bvFTD) disrupts our most human social
      and emotional functions. Early in the disease, patients show focal anterior
      cingulate cortex (ACC) and orbital frontoinsula (FI) degeneration, accentuated in
      the right hemisphere. The ACC and FI, though sometimes considered ancient in
      phylogeny, feature a large bipolar projection neuron, the von Economo neuron
      (VEN), which is found only in humans, apes, and selected whales-all large-brained
      mammals with complex social structures. In contrast to bvFTD, Alzheimer disease
      (AD) often spares social functioning, and the ACC and FI, until late in its
      course, damaging instead a posterior hippocampal-cingulo-temporal-parietal
      network involved in episodic memory retrieval. These divergent patterns of
      functional and regional impairment remain mysterious despite extensive molecular
      level characterization of bvFTD and AD. In this report, we further develop the
      hypothesis that VENs drive the regional vulnerability pattern seen in bvFTD,
      citing recent evidence from functional imaging in healthy humans, and also
      structural imaging and quantitative neuropathology data from bvFTD and AD. Our
      most recent findings suggest that bvFTD and AD target distinct, anticorrelated
      intrinsic connectivity networks and that bvFTD-related VEN injury occurs
      throughout the ACC-FI network. We suggest that the regional and neuronal
      vulnerability patterns seen in bvFTD and AD underlie the divergent impact of
      these disorders on recently evolved social-emotional functions.

PMID- 18090426
TI  - Longitudinal tracking of FTLD: toward developing clinical trial methodology.
AB  - Putative treatments for the frontotemporal lobar degenerations are likely to
      become available for testing in clinical trials in the next few years. To design
      clinical trials for this group of disorders, a number of conceptual,
      methodologic, and diagnostic issues must be resolved. This presentation reviews
      diagnostic criteria, instruments for longitudinal study, questions about study
      duration, and the possible uses of biomarkers in clinical trials. In addition, a
      multicenter trial is described in which some aspects of diagnosis and
      longitudinal measurement in the frontotemporal lobar degenerations are being
      specifically explored.

PMID- 18090427
TI  - A model for management of behavioral symptoms in frontotemporal lobar
      degeneration.
AB  - Frontotemporal lobar degeneration is a neurologic condition that manifests
      profound behavioral, personality, and language symptoms. These changes, often
      unique to each person, may include social misconduct, eating disturbances,
      apathy, emotional blunting, childlike behavior, habits and rituals, executive
      dysfunction, and marked difficulty with speech and language. These symptoms occur
      as the result of cell loss in discrete areas of the brain, the frontal and/or
      anterior temporal lobes. Little is known about effective management of the
      behavioral symptoms that result from this disease. The purpose of this paper is
      to describe a model that could be used in the assessment and potential management
      of frontotemporal lobar degeneration behavioral symptoms. Suggestions for
      interventions are given for some of the more common FTD behaviors. The impact of
      behavioral symptoms on the family caregiver is discussed along with strategies
      for supportive services and recommendations for future study.

PMID- 18090428
TI  - Rate of cognitive change measured by neuropsychologic test performance in 3
      distinct dementia syndromes.
AB  - Progressive decline in cognition is a hallmark feature of dementia, and the rate
      and profile of cognitive decline has been well characterized in Alzheimer disease
      (AD). Less is known about decline in cognition over time in other forms of
      dementia such as the behavioral variant of frontotemporal dementia (FTD) and
      primary progressive aphasia (PPA). The present study examined rate of cognitive
      decline across domains of memory, language, and executive function measured by
      neuropsychologic tests, in AD (n=84), FTD (n=66), and PPA (n=44). Patients were
      in the mild stages of dementia, with comparable duration of illness at the
      baseline evaluation. A best linear unbiased predictor (BLUP) analysis was used in
      which the slope of the relationship between a cognitive measure and time was
      estimated for each person. AD subjects demonstrated a floor effect on measures of
      memory at baseline and a decline on measures of language and executive
      functioning over time. FTD showed the greatest decline over time on the Mini
      Mental State Examination, executive functioning, and naming. PPA patients
      demonstrated prominent decline on language measures, verbal memory measures, and
      attention. Results suggest that the profile of rate of change over time has
      unique features on the basis of the type of dementia syndrome. However, there is
      overlap in the profiles of decline likely influenced by the overlap in cognitive
      constructs measured by neuropsychologic tests. The comparison of the rate of
      decline in FTD and PPA may also reflect the neuroanatomic overlap in these
      syndromes over time.

PMID- 18090429
TI  - Frontotemporal dementia treatment: current symptomatic therapies and implications
      of recent genetic, biochemical, and neuroimaging studies.
AB  - Frontotemporal dementia (FTD) is a common cause of dementia that encompasses 3
      clinical subtypes: a behavioral/dysexecutive (frontal) variant and 2 variants
      with prominent language impairments. There are currently no Food and Drug
      Administration-approved medications for FTD although symptomatic treatments such
      as selective serotonin reuptake inhibitors and atypical antipsychotic agents are
      frequently used to manage behavioral abnormalities associated with this disorder.
      Evidence for the use of currently available symptomatic treatments in each FTD
      clinical subtype is reviewed. In addition, the implications of new genetic and
      neuropathologic information about FTD for the design of future clinical trials
      and the eventual development of FTD-specific disease-modifying treatments are
      discussed.

PMID- 18090430
TI  - Primary progressive aphasia: a 25-year retrospective.
AB  - The diagnosis of primary progressive aphasia (PPA) is made in any patient in whom
      a language impairment (aphasia), caused by a neurodegenerative disease
      (progressive), constitutes the most salient aspect of the clinical picture
      (primary). The language impairment can be fluent or nonfluent and may or may not
      interfere with word comprehension. Memory for recent events is relatively
      preserved although memory scores obtained in verbally mediated tests may be
      abnormal. Lesser changes in behavior and object recognition may be present but
      are not the leading factors that bring the patient to medical attention. This
      selective clinical pattern is most conspicuous in the initial stages of the
      disease. Progressive nonfluent aphasia and some types of semantic dementia can be
      considered subtypes of PPA. Initially brought to the attention of contemporary
      literature 25 years ago, PPA has recently witnessed substantial progress related
      to its neurolinguistic features, neuroanatomy, imaging, neuropathology, genetics,
      and risk factors.

PMID- 18090433
TI  - The neighborhood as the laboratory: looking for answers by knocking on doors.

PMID- 18090435
TI  - Safety, tolerability, pharmacokinetics, and Abeta levels after short-term
      administration of R-flurbiprofen in healthy elderly individuals.
AB  - To evaluate the safety and tolerability and pharmacokinetic properties of R
      flurbiprofen (Tarenflurbil) in normal elderly individuals and to determine the
      effect of the drug on amyloid beta 42 (Abeta42) levels, we conducted a double
      blind, placebo-controlled study of 48 healthy subjects aged 55 to 80. Three
      successive cohorts were randomized to doses of 400, 800, or 1600 mg/d, or
      placebo, given as 2 divided doses for 21 days. Blood and cerebrospinal fluid were
      collected for pharmacokinetic studies and measurement of Abeta levels at baseline
      and on day 21. R-flurbiprofen was well-tolerated at all 3 doses. The compound
      penetrated the blood-brain barrier in a dose-dependent manner. From baseline to
      21 days, comparisons between study groups revealed no significant differences in
      changes of cerebrospinal fluid Abeta42 levels and no significant differences in
      changes of plasma Abeta42 levels at the time of trough drug level at 21 days of
      treatment. Further analysis of drug concentration-response for plasma samples
      showed that at the time of peak plasma concentration, higher plasma drug
      concentration was related to lower Abeta42 plasma levels (P=0.016). R
      flurbiprofen had an excellent safety profile and showed dose-dependent central
      nervous system penetration. Exploratory analyses of plasma Abeta and peak drug
      levels suggested a short-term effect in plasma that warrants independent
      verification. The safety, tolerability, and pharmacokinetic profile of R
      flurbiprofen in these older individuals support the ongoing studies of this
      compound in patients with Alzheimer disease.

PMID- 18090436
TI  - Musculoskeletal disorders in referrals for suspected lumbosacral radiculopathy.
AB  - OBJECTIVE: An electrodiagnostic evaluation is often requested for patients with
      suspected lumbosacral radiculopathy. Although musculoskeletal disorders can
      produce lower-limb symptoms, their prevalence in this referral population is
      unknown. The purpose of this study was to determine the prevalence of common
      lower-limb musculoskeletal disorders in patients referred for lower-limb
      electrodiagnosis and determine whether these findings predict study outcome.
      DESIGN: Subjects undergoing an electrodiagnostic study for lower-limb symptoms
      and suspected lumbosacral radiculopathy constituted the sample. A standardized
      clinical and electrodiagnostic evaluation was performed for all patients.
      RESULTS: There were 170 subjects included. The mean age was 52 (SD = 17), and 45%
      were males. The total prevalence of musculoskeletal disorders in the sample was
      32%. The prevalence in those with a normal study was 55% as compared with 21% in
      those with lumbosacral radiculopathy (P < 0.0001). CONCLUSIONS: Musculoskeletal
      disorders are common in patients suspected of having lumbosacral radiculopathy.
      The high prevalence among both patients with normal studies and those with
      radiculopathy and other disorders limits the usefulness of this information in
      predicting study outcome. In particular, it is common for patients to have two or
      more problems and the presence of a musculoskeletal disorder should not preclude
      such testing.

PMID- 18090437
TI  - Understanding pain after traumatic brain injury: impact on community
      participation.
AB  - OBJECTIVE: To examine the prevalence of pain 1 yr after moderate to severe
      traumatic brain injury (TBI) and identify predictors from the time of injury.
      Additionally, factors related to pain at 1 yr after injury were examined along
      with the impact of pain on community participation. DESIGN: Prospective cohort
      study of 146 individuals enrolled during acute inpatient rehabilitation for TBI
      and community follow-up at 1 yr after injury. RESULTS: Higher reports of
      depressive symptoms during inpatient rehabilitation and at 1 yr after injury were
      significantly related to reports of pain at 1 yr when controlling for demographic
      and injury characteristics. Being female and nonwhite were also factors related
      to increased reports of pain. Pain and community participation were significantly
      related until depression was entered into the model. Depression is a significant
      factor in the relationship between pain and community participation. CONCLUSION:
      Whereas pain was frequently reported 1 yr after injury, injury-related factors
      were surprisingly unrelated. Further evaluation of the role that depression plays
      in the relationship between pain and community participation will be important to
      determine appropriate management of pain and depression and to optimize
      participation in individuals with TBI.

PMID- 18090438
TI  - Myopathic dropped head syndrome: an expanding clinicopathological spectrum.
AB  - OBJECTIVE: A number of neuromuscular conditions may lead to a dropped head
      syndrome (DHS), with some patients developing a late onset noninflammatory
      myopathy affecting only, or predominantly, neck extensor muscles (NEM). The
      cause, pathogenesis, and nosological classification of this condition are
      unclear. To further investigate this condition, the authors evaluated the
      clinical, electrodiagnostic and pathologic findings in seven patients with a
      myopathic DHS. DESIGN: Analysis of clinical data, electrodiagnostic studies, and
      muscle biopsies of seven patients, including one set of identical twins, who
      developed a very late onset myopathy with severe NEM weakness. RESULTS: Age of
      onset was 61-79 yrs, with the pair of identical twins developing NEM weakness
      within 1 yr of each other (ages 63 and 64, respectively). Seven patients
      developed weakness (six slight weakness and one more severe) in muscles other
      than NEM. The group was characterized by the electromyography (EMG) showing a
      "myopathic" pattern in cervical paraspinal muscles (7/7), muscle biopsies with
      nonspecific myopathic changes on histologic stains (7/7), marked abnormalities in
      NADH dehydrogenase-reacted sections (6/7), desmin-positive sarcoplasmic deposits
      (1/7), low carnitine levels by biochemical assays (2/7), and mitochondrial
      changes (3/7). CONCLUSIONS: Myopathic DHS encompasses a wide spectrum of
      conditions that strongly affect NEM; however, as documented in the monozygotic
      twins, some patients may suffer from a distinct, genetically determined form of
      late-onset restricted myopathy leading clinically to DHS.

PMID- 18090439
TI  - Upper-limb prosthetics: critical factors in device abandonment.
AB  - OBJECTIVE: To investigate the roles of predisposing characteristics, established
      need, and enabling resources in upper-limb prosthesis use and abandonment.
      DESIGN: A self-administered, anonymous survey was designed to explore these
      factors. The questionnaire was available online and in paper format and was
      distributed through healthcare providers, community support groups, and one
      prosthesis manufacturer. Two hundred forty-two participants of all ages and
      levels of upper-limb absence completed the survey. RESULTS: Of participants, 20%
      had abandoned prosthesis use. Predisposing factors, namely, origin of limb
      absence, gender, bilateral limb absence, and, most importantly, level of limb
      absence, proved influential in the decision not to wear prostheses. Enabling
      resources such as the availability of health care, cost, and quality of training
      did not weigh heavily on prosthesis rejection, with the exception of the fitting
      time frame and the involvement of clients in the prosthesis selection.
      Conversely, the state of available technology was a highly censured factor in
      abandonment, specifically in the areas of comfort and function. Perceived need
      emerged as a predominant factor in prosthesis use. CONCLUSIONS: Future research
      should focus on continued development of more comfortable and functional
      prostheses, particularly for individuals with high-level or bilateral limb
      absence. Improved follow-up, repair, and information services, together with
      active involvement of clients in the selection of prostheses meeting their
      specific goals and needs, is recommended.

PMID- 18090440
TI  - Cyproheptadine for pediatric intrathecal baclofen withdrawal: a case report.
AB  - Intrathecal baclofen withdrawal syndrome is a known complication of intrathecal
      baclofen pumps. Its origin is postulated as an independent form of a serotonergic
      syndrome occurring from loss of gamma-aminobutyric acid B receptor-mediated
      inhibition of serotonin. Prodromal symptoms include pruritus, a return of deep
      tendon reflexes, and increased spastic hypertonia. Previous reports have
      documented use of cyproheptadine in treatment of this syndrome in adults with
      positive results. We present the case of a 14-yr-old child with cerebral palsy
      who developed pruritus and worsening spastic hypertonia 18 mos after pump
      implantation. She had been previously treated with 520 microg/day of intrathecal
      baclofen. Progression of her symptoms was successfully arrested by the
      administration of both oral and intrathecal baclofen and 6 mg of oral
      cyproheptadine every 6 hrs for 1 day. We postulate that cyproheptadine should be
      considered a valuable adjuvant therapy for treatment of suspected intrathecal
      baclofen withdrawal syndrome.

PMID- 18090434
TI  - Oxidative stress and transcriptional regulation in Alzheimer disease.
AB  - Alzheimer disease (AD) is defined by progressive impairments in memory and
      cognition and by the presence of extracellular neuritic plaques and intracellular
      neurofibrillary tangles. However, oxidative stress and impaired mitochondrial
      function always accompany AD. Mitochondria are a major site of production of free
      radicals [ie, reactive oxygen species (ROS)] and primary targets of ROS. ROS are
      cytotoxic, and evidence of ROS-induced damage to cell membranes, proteins, and
      DNA in AD is overwhelming. Nevertheless, therapies based on antioxidants have
      been disappointing. Thus, alternative strategies are necessary. ROS also act as
      signaling molecules including for transcription. Thus, chronic exposure to ROS in
      AD could activate cascades of genes. Although initially protective, prolonged
      activation may be damaging. Thus, therapeutic approaches based on modulation of
      these gene cascades may lead to effective therapies. Genes involved in several
      pathways including antioxidant defense, detoxification, inflammation, etc, are
      induced in response to oxidative stress and in AD. However, genes that are
      associated with energy metabolism, which is necessary for normal brain function,
      are mostly down-regulated. Redox-sensitive transcription factors such as
      activator protein-1, nuclear factor-kappaB, specificity protein-1, and hypoxia
      inducible factor are important in redox-dependent gene regulation. Peroxisome
      proliferators-activated receptor-gamma coactivator (PGC-1alpha) is a coactivator
      of several transcription factors and is a potent stimulator of mitochondrial
      biogenesis and respiration. Down-regulated expression of PGC-1alpha has been
      implicated in Huntington disease and in several Huntington disease animal models.
      PGC-1alpha role in regulation of ROS metabolism makes it a potential candidate
      player between ROS, mitochondria, and neurodegenerative diseases. This review
      summarizes the current progress on how oxidative stress regulates the expression
      of genes that might contribute to AD pathophysiology and the implications of the
      transcriptional modifications for AD. Finally, potential therapeutic strategies
      based on the updated understandings of redox state-dependent gene regulation in
      AD are proposed to overcome the lack of efficacy of antioxidant therapies.

PMID- 18090441
TI  - Perceived preparedness for physiatric specialization and future career goals of
      graduating postgraduate year IV residents during the 2004-2005 academic year.
AB  - OBJECTIVE: The purpose of this study was to evaluate trends among postgraduate
      year (PGY) IV physiatry residents, at the time of graduation from residency, in
      terms of their perceived experiences in the core clinical areas, confidence with
      procedural subspecialization, choice in career specialization, and desire to
      pursue clinical fellowship. DESIGN: Surveys were distributed to 386 PGY IV
      residents in physiatry at the end of the 2004-2005 academic year. RESULTS: Ninety
      three residents (24%) completed responses in a confidential manner. Residents who
      were generally more confident in core clinical areas, as defined by the Self
      Assessment Examination, and specialty prescription writing also believed
      themselves to be more prepared to practice these topics in their careers. Overall
      levels of confidence and perceived preparedness correlated positively with months
      of training and negatively with the belief in the need for postresidency
      fellowship training to incorporate these areas into clinical practice. Positive
      correlations also existed among perceived levels of preparedness in performing
      various physiatric procedures. Statistically significant differences in levels of
      confidence and preparedness existed among geographic regions when evaluating core
      physiatric subject matter. Fifty-six percent of residents who responded planned
      to pursue fellowship training, and a majority of residents intended to perform
      interventional procedures and musculoskeletal medicine in their practices.
      CONCLUSIONS: These results provide insight into how trainees perceive their
      current clinical education. With validation of measures for confidence and
      preparedness, this survey may be useful as an adjunct resource for residency
      programs to evaluate their trainees.

PMID- 18090442
TI  - Persistent hiccups during rehabilitation hospitalization: three case reports and
      review of the literature.
AB  - Persistent hiccups have been reported to occur occasionally during rehabilitation
      hospitalizations. Hiccups can interfere with patient participation and progress,
      and this can lengthen and complicate the rehabilitation hospitalization.
      Chlorpromazine, the only Food and Drug Administration-approved agent specifically
      indicated for hiccups, is often chosen as a first-line treatment. However,
      chlorpromazine does not always provide favorable results. The intent of this
      paper is to (1) review hiccups and implications of persistent hiccups in the
      rehabilitation setting, (2) provide additional evidence that chlorpromazine is
      often not the best treatment choice for hiccups in rehabilitative patients, (3)
      report the effectiveness and favorable tolerability of modest doses of gabapentin
      in a small case series of three patients, and (4) review potentially effective
      treatment approaches for hiccups.

PMID- 18090443
TI  - Persistent hiccup associated with intrathecal morphine infusion pump therapy.
AB  - Intraspinal drug-delivery therapy has been increasingly used in patients with
      intractable nonmalignant pain syndromes during the past two decades. Morphine,
      the only FDA-approved opioid for intrathecal administration, has been the
      principle agent for such therapy. Although intrathecal morphine infusion can
      produce profound spinal analgesia, it may also cause some untoward side effects.
      We describe the first case of persistent hiccup caused by intrathecal morphine
      infusion therapy.

PMID- 18090444
TI  - Ashley X.
AB  - The recent case of Ashley X has sparked much recent public debate and
      controversy, and raises critical questions for physiatrists and rehabilitation
      professionals. The case came to light when Gunther and Diekema published an
      article in the October 2006 issue of Archives of Pediatric and Adolescent
      Medicine describing a novel growth attenuation treatment for Ashley X, a 6-yr-old
      girl with developmental disabilities. Her parents also published a blog about
      Ashley, with detailed explanations for their rationale in choosing this treatment
      on behalf of Ashley which involved beliefs about her future and quality of life.
      Ashley's parents refer to the series of interventions as the Ashley Treatment in
      their blog, and this phrase has also been adopted by the popular press and others
      who have commented on the case. In this article we present an analysis of the
      Ashley X treatment and use a disability ethics approach to examine the
      perspectives of various stakeholders involved, including Ashley and other girls
      with extensive disabilities, parents, physicians, and bioethics committees. We
      conclude with critical questions for physiatrists and other disability
      specialists who are in a unique position to examine medical controversies
      involving people with disabilities.

PMID- 18090445
TI  - Exacerbation of habitual dislocation of ulnar nerve by concurrent dislocation of
      triceps muscle: complementary role of dynamic ultrasonography to
      electrodiagnosis.

PMID- 18090446
TI  - Re: introduction to nanotechnology: potential applications in physical medicine
      and rehabilitation.

PMID- 18090447
TI  - Re: sacroiliac joint pain: anatomy, biomechanics, diagnosis, and treatment.

PMID- 18090449
TI  - Re: the myofascial trigger point region: correlation between the degree of
      irritability and the prevalence of endplate noise.

PMID- 18090451
TI  - Re: characteristics and treatment of headache after traumatic brain injury.

PMID- 18090453
TI  - Re: shoulder impingement syndrome: relationships between clinical, functional,
      and radiologic findings.

PMID- 18090456
TI  - Safety, tolerability, and effects on plasma and cerebrospinal fluid amyloid-beta
      after inhibition of gamma-secretase.
AB  - OBJECTIVES: gamma-Secretase inhibitors may be useful as disease-modifying drugs
      for the treatment of Alzheimer disease. LY450139 is a gamma-secretase inhibitor
      currently in clinical development, with doses being optimized through the use of
      biomarkers. METHODS: To further characterize biomarker responses to LY450139,
      single oral doses of 60, 100, or 140 mg were administered to volunteers without
      neuropsychiatric disease. Extensive safety assessments were obtained along with
      measures of changes in amyloid-beta (Abeta) in plasma and cerebrospinal fluid
      (CSF). A measure of the change in plasma Abeta1-40 was derived (area above the
      curve), which was determined by both the magnitude and duration of Abeta1-40
      reduction. RESULTS: A total of 31 subjects (ages 49-53 years, 19 men) were
      enrolled. With the possible exception of headache, no clinically significant
      adverse events or laboratory changes were observed. A dose-proportional increase
      in drug exposure was present in plasma and in CSF. A dose-dependent change in
      plasma Abeta1-40 area above the curve was also demonstrated. Using the 140-mg
      dose, a maximum 72.6% reduction in plasma Abeta1-40 was demonstrated that did not
      return to baseline for more than 12 hours. Cerebrospinal fluid concentrations of
      Abeta were unchanged 4 hours after drug administration. CONCLUSIONS: These data
      show that single doses of LY450139 up to 140 mg are accompanied by a dose
      dependent plasma Abeta response. No response in CSF Abeta was apparent 4 hours
      after dosing.

PMID- 18090457
TI  - A naturalistic long-term comparison study of selective serotonin reuptake
      inhibitors in the treatment of panic disorder.
AB  - OBJECTIVES: Selective serotonin reuptake inhibitors (SSRIs) are currently
      considered as the first drug of choice in the treatment of panic disorder (PD).
      The aim of this long-term, naturalistic comparison study was to compare 4 SSRIs
      with respect to tolerability and treatment outcome of PD. Outcome measures
      included relapse rates and adverse effects. METHODS: Two hundred patients with PD
      were enrolled in our study. All subjects met DSM-IV criteria for PD or PD with
      agoraphobia (PDA). All patients were assigned to receive SSRI monotherapy for 12
      months with either citalopram (n = 50), fluoxetine (n = 50), fluvoxamine (n =
      50), or paroxetine (n = 50) in a randomized, nonblinded fashion. Both the
      treating psychiatrist and the patients were not blind to the assigned treatment,
      but the clinician raters were blind to the study medication. The study design
      allowed for assignment of a particular SSRI as indicated according to the
      clinical judgment of the study psychiatrists. The Panic Self-Questionnaire, which
      is a self-report scale, was administered at baseline and then once per month
      during the duration of the 12-month study. The visual analog scale and the
      Clinical Global Impression Scale were administered at baseline and then once per
      month during the period of the study. Reports of sexual dysfunction were assessed
      using a nonstructured clinical interview at monthly visits. The body weight of
      study subjects was measured at baseline, and then at the 12th month visit end
      point. RESULTS: Of 200 patients who entered the study, 127 patients (63.5%)
      completed the full 12-month protocol. Retention rates were highest for paroxetine
      (76% [38/50]), intermediate for citalopram (68% [34/50]) and fluvoxamine (60%
      [30/50]), and lowest for fluoxetine (50% [25/50]). Patients who completed the 12
      month protocol responded favorably to the study treatment. The paroxetine and the
      citalopram groups had significantly lower rates of panic symptoms as measured at
      visits on weeks 4 and 8. At visits on months 3, 6, 9, and 12, however, there were
      no statistically significant differences between the 4 groups in relapse rates
      (defined as the occurrence of 1 or more panic attacks during the previous week of
      treatment) (F1,127 = 0.17; P = 0.13 [not statistically significant]). At the 12th
      month end point, patients in all 4 treatment groups had a statistically
      significant increase in body weight. Body weight among the study population
      increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of
      treatment. Reports of sexual adverse effects at the 12th month visit were similar
      in the citalopram, fluoxetine, and paroxetine groups, but the fluvoxamine patient
      group reported fewer sexual adverse effects at the 12th month visit. CONCLUSIONS:
      Most of our PD patients responded well to 12-month treatment with either
      citalopram, fluoxetine, fluvoxamine, or paroxetine, and the overall response rate
      was equal after the first 4 weeks of treatment. Although patients treated with
      paroxetine had the lowest dropout rates during the initiation phase, they had the
      highest rate of adverse effects as measured at the 12th month visit. Conversely,
      patients in the fluvoxamine group had the highest dropout rate (which was
      primarily caused by adverse effects in the initiation phase of treatment.);
      however, patients who were able to tolerate fluvoxamine throughout the full
      course of the study were observed to have lower rates of sexual dysfunction and
      weight gain compared with patients treated with the other agents. Overall, when
      measured at the 12th month visit, monotherapy with paroxetine and citalopram was
      associated with a higher rate of sexual adverse effects than was treatment with
      fluoxetine or fluvoxamine. In addition, monotherapy with paroxetine, citalopram,
      and fluoxetine seemed to cause more weight gain than did treatment with
      fluvoxamine.

PMID- 18090458
TI  - Entacapone prolongs the reduction of PLM by levodopa/carbidopa in restless legs
      syndrome.
AB  - OBJECTIVES: Levodopa is effective in the treatment of restless legs syndrome
      (RLS). However, due to the short duration of action of conventional
      levodopa/decarboxylase inhibitor formulations, multiple dosing may be required in
      individual patients with persisting symptoms. We assessed whether a new levodopa
      formulation containing levodopa, carbidopa, and entacapone (LCE) improves
      levodopa action in RLS. METHODS: Twenty-eight RLS patients with periodic limb
      movement (PLM) received single doses of Stalevo 50 (LCE50; 50/12.5/200 mg),
      Stalevo 100 (LCE100; 100/25/200 mg), Stalevo 150 (LCE150; 150/37.5/200 mg),
      Sinemet 100 (LC100; 100/25 mg), or placebo in a randomized, double-blind,
      crossover study with polysomnography. Periodic limb movements per hour (PLM/h)
      during total sleep time and PLM during total time in bed were the primary and
      secondary variables, respectively. RESULTS: Mean PLM/h during total sleep time
      after Stalevo 50 (12.6/h, P < 0.05), LCE100, LCE150, and LC100 (6.4/h, 3.5/h and
      9.5/h, respectively; P < 0.01) were significantly reduced compared with placebo
      (25.7/h). Improvement was also observed in PLM/h during total time in bed for all
      treatments (P < 0.01) and a significant dose response observed between LCE doses
      (P < 0.05). Compared with LC100, LCE100 and LCE150 reduced PLMs during the second
      half (P = 0.06 and P < 0.001, respectively) or during the last 3 early morning
      hours (hours 5-7 from the start of recording) of the night (P < 0.05 and P <
      0.01, respectively). All formulations were well tolerated. CONCLUSIONS: Single
      doses of LCE tablets decreased PLMs in a dose-related manner in RLS patients.
      Prolonged effects of levodopa on PLMs suggest that, compared with standard
      levodopa, this new levodopa formulation provides longer symptom control
      throughout the night in patients with previously untreated RLS.

PMID- 18090459
TI  - Zonisamide for essential tremor.
AB  - OBJECTIVE: The pharmacological therapy for essential tremor (ET) is inadequate,
      and many patients resort to surgical procedures. Zonisamide is an antiepileptic
      with several potential mechanisms of action. MATERIALS AND METHODS: We evaluated
      zonisamide for ET in an open-label pilot trial. The primary efficacy point was
      the change in the Tremor Study Group rating scale (TSGRS) scores. RESULTS: Twenty
      two subjects were enrolled (male, 9; mean age +/- SD, 65.0 +/- 12.6 years; mean
      duration of ET +/- SD, 25.6 +/- 17.1 years). Six subjects dropped because of
      either (1) adverse events (AEs) and lack of effect (n = 4) or (2) lack of effect
      (n = 2). Two were lost to follow-up. Fourteen subjects returned for their
      complete postmedication evaluation. After 3 months (mean +/- SD, 88 +/- 34 days),
      the final dose was 200 mg (n = 11), 150 mg (n = 1), 100mg (n = 1), and 12.5 mg (n
      = 1). The mean Tremor Study Group rating scale scores improved from a mean of
      28.9 (SD, +/-9.2) to a mean of 21.1 (SD, +/-6.5) (P = 0.02, unpaired t test).
      Seven subjects (50%) had at least a 25% improvement. Subjectively, however, only
      4 reported marked or moderate improvement, 3 reported mild improvement, and 7
      reported no change. Adverse events included decreased concentration/cognition (n
      = 2), constipation (n = 1), nocturia (n = 1), abdominal pain/diarrhea (n = 1),
      and sedation (n = 1). CONCLUSIONS: Zonisamide significantly (albeit modestly)
      improved the TSGRS scores in this small group of medically refractory subjects
      who completed the evaluation. However, clinical impressions did not improve, and
      the study was complicated by a large dropout rate caused by subjective lack of
      efficacy and by AEs.

PMID- 18090460
TI  - Levetiracetam is not effective for essential tremor.
AB  - OBJECTIVE: To determine if levetiracetam is efficacious in the treatment of
      essential tremor. METHODS: Fifteen patients (3 women), aged 35 to 83 years, with
      essential tremor were studied in a double-blind, placebo-controlled crossover
      trial of levetiracetam. During the 2 treatment periods, levetiracetam or placebo
      was titrated from 500 to 3000 mg/d during a 5-week titration phase, as tolerated,
      and the maximum tolerated dosage was then maintained for 4 weeks. There was a 3
      week washout phase between the 2 treatment periods. Patients were assessed with
      the Fahn-Tolosa-Marin tremor rating scale (TRS), and tremor in the spiral and
      line drawings of 7 patients was quantified with a computerized digitizing tablet.
      Changes in other antitremor medications (10 patients) were not permitted during
      the study. RESULTS: The planned enrollment of 45 patients was stopped when an
      interim analysis of the first 15 patients revealed no efficacy. One patient
      failed to achieve the 3000-mg/d dosage of levetiracetam. Three patients dropped
      out of the study due to lack of efficacy and other side effects. The analysis of
      TRS data with these three patients excluded and after imputing their missing data
      (last value carried forward) revealed a statistically insignificant trend for all
      TRS and tablet measures to be worse when patients were taking levetiracetam.
      There was no period effect or treatment-period interaction for any measure of
      tremor. The results were the same for the 5 patients taking no other antitremor
      medications. CONCLUSIONS: Levetiracetam is not beneficial in the treatment of
      essential tremor.

PMID- 18090461
TI  - Ziprasidone-associated depressive state in schizophrenic patients.
AB  - OBJECTIVES: Although depression is a recognized side effect of many medications,
      the association of this condition with neuroleptics has received limited
      attention in the literature. Atypical antipsychotics may demonstrate a beneficial
      effect on affective symptoms. On the other hand, they may also cause depression
      both in those with and without a history of psychiatric illness. Although
      ziprasidone has been reported to have antidepressive properties, we are not aware
      of reports regarding ziprasidone-induced depression. METHODS: We describe 3 cases
      of ziprasidone-associated depression in patients treated for schizophrenia who
      had no previous history of depressive illness. To the best of our knowledge, this
      is the first description of such an association. CONCLUSIONS: This case series
      suggests that atypical antipsychotics may have a causal relationship in the
      development of depression in schizophrenic patients. This is noteworthy because
      these medications have been found in the past to have an antidepressant action.
      If neuroleptic-induced depression is mistaken for negative symptoms of
      schizophrenia, this condition may go untreated. Further data based on controlled
      studies are required.

PMID- 18090462
TI  - Dosing and therapeutic monitoring of phenytoin in young adults after neurotrauma:
      are current practices relevant?
AB  - Anticonvulsant drugs are commonly used to treat and prevent seizures after
      neurotrauma. However, many physiological changes occur in the neurotrauma
      patient, which alter the pharmacokinetics of drugs such as phenytoin. This raises
      concerns relating to the dosage and monitoring of phenytoin in these patients
      compared with its routine use in epileptic patients. Examples of pharmacokinetic
      alterations within the neurotrauma patient include changes in hepatic metabolism,
      protein binding alterations, and disruption of the blood-brain barrier. Drug
      interactions and genetic factors may also contribute to pharmacokinetic
      variations. Many studies have reported that neurotrauma patients often present
      with either subtherapeutic or highly variable phenytoin serum concentrations.
      When phenytoin doses recommended for the epileptic patient are used in the
      neurotrauma patient, efficacy is limited to early posttraumatic seizures, with no
      effect on morbidity, mortality, or the onset of late posttraumatic seizures. This
      review examines the effect of neurotrauma on the pharmacokinetics of phenytoin
      alongside clinical outcomes and questions the current dosing and therapeutic
      monitoring practices within this area.

PMID- 18090463
TI  - Reversible Pisa syndrome induced by clozapine: a case report.
AB  - Pisa syndrome, manifested with persistent lateral flexion of the trunk, is most
      commonly associated with prolonged treatment with typical antipsychotics.
      However, it was also reported as occurring with atypical antipsychotics. To our
      knowledge, there have been very few reports of clozapine-associated Pisa
      syndrome. Here we report 1 case of Pisa syndrome in a 39-year-old woman with
      schizoaffective disorder who developed tonic flexion of trunk and head toward the
      left side after clozapine treatment (400 mg/d) for 5 months. Clozapine was
      reduced to 25 mg/d within 15 days; the dystonic reaction then completely resolved
      within the next 3 to 4 weeks. Caution should be taken while prolonged use of
      clozapine in patients with risk factors of Pisa syndrome.

PMID- 18090466
TI  - Arthrokatadysis of the hip joint.

PMID- 18090467
TI  - Intrapelvic protrusion of the acetabulum (Otto pelvis). 1932.

PMID- 18090469
TI  - Minimum 6-year followup of highly cross-linked polyethylene in THA.
AB  - To reduce wear rates and particulate debris, highly cross-linked polyethylene has
      been in use in total hip arthroplasty for 8 years. We designed this followup
      study to primarily determine the total penetration rate of the femoral head and
      the steady-state wear rate of cross-linked polyethylene in patients undergoing
      primary total hip arthroplasty. We retrospectively reviewed data from 182
      patients (200 hips) with a minimum 6-year followup (mean, 6.9 years; range, 6-8
      years) and an average age of 60.2 years at surgery. The average Harris hip score,
      University of California-Los Angeles activity score, and WOMAC score were 91.1,
      6.3, and 11.3, respectively. Radiographic evaluation showed no evidence of
      loosening or osteolytic lesions around the cup or stem. No revisions were
      performed for polyethylene wear or liner fracture. The average steady-state wear
      rate was -0.002 +/- 0.01 mm per year and -0.026 +/- 0.13 mm per year for 28-mm
      and 32-mm head sizes, respectively. We observed no correlation between the total
      wear rate and femoral head size, brand of polyethylene, age, gender, primary
      diagnosis, mode of fixation, surgical approach, University of California-Los
      Angeles activity score, Harris hip score, or WOMAC. Highly cross-linked
      polyethylene liners are associated with excellent midterm clinical, radiographic,
      and wear results in this group of patients.

PMID- 18090468
TI  - The 2007 Otto Aufranc Award. Ceramic-on-metal hip arthroplasties: a comparative
      in vitro and in vivo study.
AB  - The performance of novel ceramic-on-metal bearing couples has been compared with
      metal-on-metal and ceramic-on-ceramic bearing couples in laboratory and short
      term clinical studies. Laboratory studies compared ceramic-on-metal with metal-on
      metal and ceramic-on-ceramic bearings with diameters of 28 and 36 mm under
      standard conditions and under adverse conditions with head loading on the rim of
      the cup. Clinical studies compared metal ion levels in ceramic-on-metal with
      metal-on-metal, ceramic-on-ceramic, and ceramic-on-polyethylene bearings in a
      randomized prospective study. In the laboratory studies, friction, wear, and ion
      levels were lower in ceramic-on-metal bearings compared with metal-on-metal, with
      results similar to ceramic-on-ceramic couples. Under adverse conditions and rim
      loading, all bearings showed increased wear with lower wear and absence of stripe
      wear in ceramic-on-metal compared with metal-on-metal bearings. Short-term
      studies in 31 patients at 6 months revealed lower metal ion levels (cobalt and
      chromium) in those with ceramic-on-metal compared with metal-on-metal bearings.

PMID- 18090470
TI  - Remelting of highly cross-linked polyethylene worn under laboratory conditions.
AB  - It has been suggested that apparent wear damage in highly cross-linked
      polyethylene acetabular liners can be removed with subsequent remelting of
      retrieved liners. To test this hypothesis, we remelted liners that had been
      previously tested under controlled laboratory conditions and that had experienced
      nonzero wear rates and visible wear damage. Five liner groups were examined:
      three with a range of irradiation doses without heat treatment, and two
      irradiated to 100 kGys, one with remelting, and the other annealing. All groups
      had been worn in a hip simulator under impingement conditions that produced
      nonzero wear rates and loss of machining marks. Each liner was cut into quadrants
      that were graded for wear damage before and after posttest remelting. Cross
      linked liners not previously heat-treated lost all prior damage and all machining
      marks. Remelted liners and three of six annealed liners experienced only a slight
      return of machining marks at the interface of the burnished area and the
      remaining intact machining marks. Our experiments represent a severe wear case
      but demonstrate removal of material from the surface through measurable wear
      prevents the return of identifiable machining marks despite remelting.

PMID- 18090472
TI  - The importance of range of motion after total hip arthroplasty.
AB  - Unlike the knee, range of motion has been of questionable value in evaluating
      clinical outcome after THA. We retrospectively analyzed the ranges of motion
      (flexion, abduction, adduction, external rotation, internal rotation, and flexion
      contracture) of 1383 patients (1517 hips) having primary THA. We recorded Harris
      hip score components for walking distance, stair climbing, socks and shoes,
      sitting, pain, presence of limp, and use of support devices. Postoperative hip
      motion was defined as high (115 degrees of flexion, 25 degrees of abduction, 20
      degrees of external rotation, and less than 20 degrees of flexion contracture),
      average (90 degrees -114 degrees of flexion, 16 degrees -24 degrees of abduction,
      or 11 degrees -19 degrees of external rotation, and less than 20 degrees of
      flexion contracture), or low (less than 90 degrees of flexion, 15 degrees or less
      of abduction, 10 degrees or less of external rotation, or 20 degrees or more of
      flexion contracture) motion. We correlated this with high, average, or poor
      postoperative Harris hip scores. Hip motion was found to be correlated with
      postoperative hip function and may be more useful than previously thought in
      evaluating hip outcome.

PMID- 18090471
TI  - Association of third body embedment with rim damage in retrieved acetabular
      liners.
AB  - Third-body effects are a major cause of the substantial variability of wear in
      total hip replacements. One potential mechanism by which third-body debris can
      access wear-critical central regions of closely conforming metal-on-polyethylene
      bearing couples is by fluid convection during incidents of subluxation
      accompanying neck-on-liner impingement. To provide evidence for this premise, we
      determined the association of severity of liner rim indentation damage
      (indicative of impingement frequency/vigor) and the presence of embedded third
      body debris in 194 implants retrieved at revision. Rim damage was graded using
      the five-point Hospital for Special Surgery scale. Particle embedment was
      assessed both manually and by means of an image analysis computer program that
      detected the composition, size, and location of each particle. Sixty-eight
      percent of the cups showed rim indentation damage. We found an association
      between severity of rim damage and presence of embedded debris. There was
      substantial nonuniformity of the spatial distribution of the embedded debris,
      with the predominance of embedded debris at intermediate latitudes. These
      findings support the premise of convection of debris-laden joint fluid during
      lever-out subluxation as a mechanism for wear-consequential third-body particles
      to gain access to highly loaded regions of the bearing surface, thus potentiating
      increased wear.

PMID- 18090473
TI  - The impact of resident teaching on total hip arthroplasty.
AB  - The author asked whether THA cases performed with major resident participation in
      a private practice setting were associated with greater use of health care
      resources, higher rates of technical errors, or a reduction in quality of outcome
      compared to THA cases performed without major resident involvement. Eighty-eight
      primary THA cases performed with major resident participation were compared to 61
      cases without major resident participation. Resident cases took 20 minutes
      longer, required a second assistant more frequently (92% versus 23%) but did not
      have higher transfusion rates or result in a longer hospital stay. Resident cases
      did not have more complications or increased technical errors. Resident cases
      also did not have lower Harris hip scores or inferior Short Form SF-12 physical
      ratings at minimum 1-year followup.

PMID- 18090474
TI  - Hyaluronan suppresses IL-1beta-induced metalloproteinase activity from synovial
      tissue.
AB  - Intraarticular injection of hyaluronan (viscosupplementation) is commonly used to
      treat knee pain from osteoarthritis. The therapeutic benefit might derive from
      hyaluronan inhibition of the activity of the cytokine-regulated catabolic enzymes
      that attack joint cartilage (matrix metalloproteinases). We tested the hypothesis
      that hyaluronan inhibited interleukin-1beta-induced matrix metalloproteinase
      activity secreted by explants of synovial tissue from patients with
      osteoarthritis and investigated the mechanism of the effect. Hyaluronan with a
      molecular mass of 12.8 MDa (number average) antagonized induced metalloproteinase
      activity in proportion to hyaluronan concentration in the clinically relevant
      range of 2 to 8 mg/mL. The effect was not attributable solely to molecular mass
      because 1.2-MDa hyaluronan produced comparable inhibition. Based on measurements
      involving hyaluronans of different average molecular masses, polydispersity and
      viscosity were similarly ruled out as primary responsible factors. The effect of
      hyaluronan on induced metalloproteinase activity was mediated partially by CD44,
      the principal cell surface receptor for hyaluronan. Hyaluronan inhibited
      interleukin-1beta-induced metalloproteinase production from osteoarthritic
      synovial tissue by a process that was not solely dependent on hyaluronan
      molecular mass but that was partly mediated by hyaluronan binding to CD44. The
      efficacy of viscosupplementation could be explained if hyaluronan also blocked
      catabolic enzyme activity in the joint.

PMID- 18090475
TI  - 50 years ago in CORR: Central fractures of the acetabulum by Robert B. Elliott,
      MD, FACS.

PMID- 18090481
TI  - Molecular markers in bladder cancer.
AB  - PURPOSE OF REVIEW: Bladder cancer is a diverse disease whose molecular phenotypes
      are being elucidated. In this review, we summarize currently known molecular
      pathways and associated markers in bladder cancer. RECENT FINDINGS: Genetic and
      epigenetic aberrations have been closely associated with tumor pathogenesis and
      prognosis. Cell cycle markers have been most extensively studied. More recently,
      apoptotic and angiogenic pathways are being investigated. Studying the role of
      multiple concurrent molecular alterations improves the prognostic ability of
      these markers. The use of tissue microarrays and high-throughput molecular
      profiling is accelerating the discovery of new markers. SUMMARY: Molecular
      biology is paramount to our understanding of bladder cancer pathogenesis. The
      search for new markers, and elucidating cross-talk between markers in different
      pathways, is warranted. Molecular markers have the potential benefit of improving
      detection, prognosis and treatment of bladder cancer. In addition, understanding
      the molecular profile of the individual patient could usher us into a new era of
      improving prediction of the natural history of the disease and providing a more
      personalized and tailored treatment. Prospective trials are still needed,
      however, to objectively establish the true benefit of these markers in prognostic
      and therapeutic arenas.

PMID- 18090483
TI  - The role of anticholinergic drugs in men with lower urinary tract symptoms.
AB  - PURPOSE OF REVIEW: Male lower urinary tract symptoms are often attributed to
      benign prostatic hyperplasia. However, coexisting overactive bladder may be
      responsible for storage symptoms in a substantial proportion. Treatment of these
      symptoms with anticholinergic drugs has been considered hazardous in benign
      prostatic hyperplasia because of concerns that they may predispose to acute
      urinary retention. We present recent research evidence on the effectiveness and
      safety of anticholinergics for male lower urinary tract symptoms. RECENT
      FINDINGS: Two systematic reviews and a large randomized controlled trial recently
      evaluated anticholinergic drugs in men with lower urinary tract symptoms. These
      studies provided good evidence that anticholinergics are effective at improving
      both urodynamic and patient-reported outcomes. Postvoid residual urine volumes
      and urine flow rates were not significantly affected, and acute urinary retention
      was rare. SUMMARY: In men with lower urinary tract symptoms treatment may need to
      be directed at both the prostate and the bladder, and a pragmatic approach
      therefore seems appropriate. Men presenting with lower urinary tract symptoms
      should undergo comprehensive clinical evaluation before benign prostatic
      hyperplasia is treated, if indicated. Should symptoms fail to resolve, addition
      of anticholinergic drugs may be considered in the absence of significant postvoid
      residual urine volumes.

PMID- 18090484
TI  - Plant extracts: sense or nonsense?
AB  - PURPOSE OF REVIEW: To assess the current role of plant extracts in the medical
      management of lower urinary tract symptoms due to benign prostatic
      enlargement/benign prostatic obstruction. RECENT FINDINGS: In 2006, two clinical
      trials meeting the WHO benign prostatic hyperplasia consensus conference criteria
      (randomized against placebo/standard therapy, study duration 12 months) were
      published. One trial compared a saw palmetto extract with placebo. This industry
      independent trial published in the New England Journal of Medicine was negative,
      that is, this saw palmetto extract had no effect on symptoms, Qmax and postvoid
      residual volume. In another trial, a saw palmetto/urtica combination was compared
      with tamsulosin. After 12 months, the improvement of symptoms was identical in
      both study arms. No detailed data were presented, however, on Qmax, postvoid
      residual or prostate volume. The biological mechanisms of plant extracts in vivo
      are still unknown and the numerous metaanalyses cannot supplement high-quality
      prospective trials. SUMMARY: Further prospective studies according to WHO benign
      prostatic hyperplasia standards are required to reliably determine the role of
      plant extracts in contemporary lower urinary tract symptoms management and to be
      able to answer the question in the title: 'plant extracts: sense or nonsense?'
      Plant extracts are currently not recommended by the American and European
      Association of Urology benign prostatic hyperplasia guidelines.

PMID- 18090485
TI  - Nonablative minimally invasive thermal therapies in the treatment of symptomatic
      benign prostatic hyperplasia.
AB  - PURPOSE OF REVIEW: As all new treatment modalities nonablative thermal therapy
      for minimal invasive treatment of benign prostatic hyperplasia should be
      critically analyzed. This review discusses the literature to identify the merits
      of these so-called minimally invasive treatments and the place they should take
      in the armamentarium of benign prostatic hyperplasia therapy options. RECENT
      FINDINGS: In this review we analyze the different techniques and clinical studies
      of hot water induced thermotherapy, transurethral microwave thermotherapy,
      transurethral needle ablation and high intensity focused ultrasound. The high
      intensity focused ultrasound treatment is noninvasive, but due to the poor
      clinical results in benign prostatic hyperplasia and its need for anesthesia,
      this therapeutic option shifted towards the selective ablation of prostate
      cancer. The transurethral needle ablation treatment can be performed in an
      outpatient setting although most centers do not. The treatment is not suitable
      for the bigger prostates and therefore narrows its indication. Water induced
      thermotherapy is a very promising therapy, although without comparative studies a
      justified positioning remains difficult. SUMMARY: Of all nonablative thermal
      therapies, transurethral microwave thermotherapy is the best documented and with
      several randomized studies comparing transurethral microwave thermotherapy to
      surgical treatments of the prostate, this therapy definitively found its place as
      a serious alternative to the ablative surgical treatment options.

PMID- 18090486
TI  - Injectables in the prostate.
AB  - PURPOSE OF REVIEW: Benign prostatic hyperplasia with associated symptoms and
      morbidity is increasingly common among aging men. Medical treatment of lower
      urinary tract symptoms is the mainstay of therapy with progressive disease
      requiring more invasive intervention. Transurethral resection of the prostate
      remains a widely applied gold standard therapy. Numerous minimally invasive
      surgical therapy options have arisen and subsequently faded over recent years.
      Those remaining in use are largely positioned between pharmacological treatment
      and transurethral resection of the prostate. Intraprostatic injection therapy,
      the oldest minimally invasive surgical therapy, has been investigated for over
      100 years with renewed interest recently. This review will provide some history
      of intraprostatic injection for benign prostatic hyperplasia including the most
      recent reports using transperineal, transrectal and transurethral routes with
      different injectables. RECENT FINDINGS: For benign prostatic hyperplasia,
      transperineal and transurethral injection routes have received the most
      systematic evaluation. Intraprostatic injection of botulinum toxin type A has
      received much recent attention with regards to mechanism of action and efficacy.
      Anhydrous ethanol remains the most extensively studied injectable to date.
      SUMMARY: Injection therapy remains a very promising minimally invasive surgical
      therapy for benign prostatic hyperplasia with increased attention from the
      urologic community in recent years. Further experience both with systematic
      laboratory and clinical trials investigation will be necessary before widespread
      clinical adoption.

PMID- 18090487
TI  - Open adenomectomy: past, present and future.
AB  - PURPOSE OF REVIEW: Open surgery has been the gold standard for the treatment of
      benign, symptomatic, large volume prostatic hyperplasia. Recent data series,
      however, have demonstrated that a minimally invasive approach can be used for the
      treatment of this pathology while duplicating the results of the open technique.
      This review will describe the different surgical techniques that have been used
      through the last century for the treatment of benign prostatic hyperplasia,
      highlighting the advantages and disadvantages of each approach. RECENT FINDINGS:
      Surgical management for symptomatic benign prostatic hyperplasia has made a
      journey from an open approach to robotic surgery. Modifications of the gold
      standard transurethral resection have been incorporated into clinical practice
      and include bipolar transurethral resection as well as holmium laser resection
      and potassium titanyl phosphate laser vaporization. Minimally invasive ablative
      techniques have also been popularized and include transurethral needle ablation
      and thermotherapy. Most recently, laparoscopy has demonstrated to be a feasible,
      safe, reproducible technique that can create similar outcomes to an open
      technique whilst maintaining the advantages of a minimally invasive approach.
      Although the future will see greater use of robotics, larger series are needed to
      prove the advantages of this technology. SUMMARY: Minimally invasive approaches
      for the treatment of symptomatic benign giant prostatic hyperplasia are replacing
      open surgery, which has been the gold standard for the surgical treatment of this
      pathology, duplicating its results with a lower morbidity. Recently we have seen
      a growing amount of experience treating this disease state with
      laparoscopic/robotics and the advantages it provides may permit the
      popularization of this technique.

PMID- 18090488
TI  - Holmium laser for benign prostatic hyperplasia.
AB  - PURPOSE OF REVIEW: The following review provides an overview of the current
      status, while focusing on the surgical techniques associated with the holmium
      laser for the treatment of benign prostatic hyperplasia. RECENT FINDINGS: A
      systematic Medline database search, with a focus on articles about surgical
      treatment with holmium laser for benign prostatic hyperplasia, provided some new
      data concerning holmium laser enucleation of the prostate. On the other hand, new
      interesting data concerning both resection and ablation techniques using the
      holmium laser have only been sparsely reported during this review period.
      SUMMARY: Holmium laser enucleation of the prostate is a safe procedure for
      treating not only patients without co-morbidities but also patients with urinary
      retention or who are on anticoagulants. Holmium laser enucleation of the prostate
      can be performed on prostates of all sizes with significantly less morbidity.
      Although holmium laser enucleation of the prostate represents a state-of-the-art
      procedure, a prolonged learning curve has still prevented the widespread adoption
      of this device in the urological community.

PMID- 18090489
TI  - Greenlight laser in benign prostatic hyperplasia: turning green into gold.
AB  - PURPOSE OF REVIEW: The purpose of this review is to present recent clinical data
      published upon the photoselective vaporization of the prostate procedure and
      introduce new ideas about the future influence of this new technology upon the
      treatment of benign prostatic hyperplasia. RECENT FINDINGS: Published studies
      have provided significant evidence that the photoselective vaporization of the
      prostate laser procedure is efficient, safe, easy to learn and early results show
      that it can compete with transurethral resection of the prostate. The major
      advantages of this technique are that it is a bloodless procedure, the patient
      goes home after a few hours and it can be applied to all patient categories. The
      cost of the photoselective vaporization of the prostate procedure is being
      investigated and a few studies addressing this issue seem to conclude that this
      surgical option is a cost effective decision. Lately, thoughts about early
      surgical intervention with the photoselective vaporization of the prostate laser
      are being expressed but properly designed studies are needed. SUMMARY: The
      photoselective vaporization of the prostate laser procedure is getting worldwide
      fast recognition and it is the first time that transurethral resection of the
      prostate and open prostatectomy are being threatened. The cost of this procedure
      is being examined but it is difficult to draw solid conclusions since
      reimbursement strategies differ between various countries.

PMID- 18090490
TI  - Bipolar transurethral resection of prostate: a new reference standard?
AB  - PURPOSE OF REVIEW: Transurethral resection of prostate is the gold standard for
      the surgical management of benign prostate hyperplasia. Bipolar devices allow
      transurethral resection of prostate with saline irrigation, which lessens water
      intoxication and negates the need for diathermy pad and unwanted stimulation of
      the obturator nerves and cardiac devices. Several randomized clinical trials
      compare the various bipolar devices with conventional monopolar ones. For this
      review, we search all peer-reviewed published literature databases and present
      the evidence from them to substantiate its advantages and disadvantages. RECENT
      FINDINGS: Of the various types of bipolar devices, Gyrus has the longest clinical
      experience. Bipolar transurethral resection of prostate overcomes the
      shortcomings of bipolar transurethral prostate vaporization, which includes the
      absence of histology, postop irritative urinary symptoms and nondurable clinical
      outcomes. With bipolar transurethral resection of prostate, there is lesser
      bleeding which leads to shorter resection time and lower fluid absorption. This
      also enables shorter cathterization time and hospital stay. Transurethral
      resection syndrome has not been observed. SUMMARY: Bipolar transurethral
      resection of prostate has demonstrated similar clinical efficacy as monopolar
      transurethral resection of prostate with shorter catheterization and hospital
      stay. It eliminates the occurrence of transurethral resection syndrome and
      minimizes bleeding risk. Long term outcomes from these randomized clinical trials
      will determine the durability of its clinical efficacy and incidence of urethral
      strictures.

PMID- 18090491
TI  - Translation of benign prostatic hyperplasia guidelines into clinical practice.
AB  - PURPOSE OF REVIEW: The aim of this article is to describe the current position of
      clinical practice guidelines for benign prostatic hyperplasia in daily management
      and identify the potential barriers that may hinder the implementation of
      guidelines into clinical practice. RECENT FINDINGS: Recent studies have attempted
      to compare and grade benign prostatic hyperplasia clinical practice guidelines
      using appraisal instruments underlining the issues of quality and updates of
      guidelines. Surveys have evaluated the adoption of guidelines from the urological
      community and recent studies have made major contributions to our knowledge of
      the translation of evidence to daily practice. SUMMARY: Numerous clinical
      practice guidelines (both national and international) for benign prostatic
      hyperplasia exist. High methodological quality clinical practice guidelines are
      likely to be the most beneficial to patients and strength of recommendations
      depends on available evidence. Efforts to implement guidelines are not always
      successful and a considerable variation especially in diagnostic assessment of
      benign prostatic hyperplasia has been reported. Difficulties in translation of
      benign prostatic hyperplasia guidelines into clinical practice are related to
      lack of knowledge but also to differences in routine practices, beliefs, cost,
      availability, and reimbursement policy. Bridging the implementation gap
      represents a challenging task for clinical practice guideline supporters.

PMID- 18090492
TI  - Imaging in urology - looking forward.

PMID- 18090493
TI  - Advances in positron emission tomography applications for urologic cancers.
AB  - PURPOSE OF REVIEW: Molecular imaging in oncology utilizes advances in imaging
      technology with probes that image key molecules and molecular based events that
      are fundamental for malignant change and progression. PET in combination with
      computed tomography will be the means by which molecular imaging will be
      translated into the advanced practice of urology. This review introduces the
      concept of molecular imaging and summarizes current and future molecular imaging
      approaches that are likely to have a major impact on clinical practice in the
      near future. RECENT FINDINGS: In renal cancer, a radiolabeled antibody, iodine
      124 cG250, shows promise for improving management of small clear-cell renal
      cancers through noninvasive immunologic identification as a basis for
      differential diagnosis of other renal masses. In prostate cancer, antibodies to
      key antigens, such as prostate specific membrane antigen, along with metabolic
      probes, for glycolysis (fluorodeoxyglucose) and amino acid transport (C-11
      methionine) are likely to improve early detection of regional and distant
      metastases and provide a basis for improved monitoring of treatment response.
      SUMMARY: Molecular imaging, through PET/computed tomography will help
      individualize patient care for surgical urology. Applications will include
      noninvasive image-based immunotyping of human cancers and metabolic based
      staging, detection and treatment monitoring for urologic malignancies.

PMID- 18090495
TI  - Imaging low-risk prostate cancer.
AB  - PURPOSE OF REVIEW: Prostate-specific antigen screening has led to a downstaging
      of prostate cancer that has resulted in overdiagnosis and overtreatment of the
      disease. The review discusses the potential role of imaging in identifying low
      risk prostate cancer and enabling more appropriate management of the disease.
      RECENT FINDINGS: Clinical nomograms have been designed and validated for
      prediction of the probability of insignificant prostate cancer. The models
      integrate clinical and biopsy findings. Recently, nomogram models have been
      designed that incorporate MRI and magnetic resonance spectroscopic imaging data
      with clinical and biopsy data for prediction of insignificant prostate cancer;
      these models performed better than the clinical models. SUMMARY: Clinical
      nomograms for the prediction of insignificant disease provide more information
      than any diagnostic test alone; furthermore, nomograms that incorporate MRI or
      MRI/magnetic resonance spectroscopic imaging findings with clinical and biopsy
      data have been shown to improve the prediction of insignificant cancer. A greater
      level of certainty, however, is still needed to help segregate low-risk patients
      from intermediate and high-risk patients. Therefore, more research is needed on
      imaging of low-risk prostate cancer so that data-driven, evidence-based practice
      guidelines in oncology combining anatomical, metabolic and laboratory data can be
      designed.

PMID- 18090496
TI  - The role of imaging in the detection of prostate cancer local recurrence after
      radiation therapy and surgery.
AB  - PURPOSE OF REVIEW: The aim of this article is to review novel MRI and nuclear
      medicine methods for detecting and planning salvage treatment for prostate cancer
      local recurrence after radical prostatectomy or radiation therapy. RECENT
      FINDINGS: Traditional methods for detecting local recurrence (i.e., digital
      rectal exam or transrectal ultrasound and digital rectal exam or transrectal
      ultrasound-guided biopsy) have limited accuracy in determining the presence and
      extent of local recurrence and therefore have limited ability to guide salvage
      therapy. Recent studies indicate that conventional T1 and T2-weighted prostate
      MRI could improve the detection of recurrent prostate cancer after radical
      prostatectomy or radiation therapy and salvage treatment planning. Promising new
      sequences could further increase the accuracy of MRI. In addition, the use of
      technically improved PET/computed tomography scanners with new tracers like (11)C
      and (18)F choline and acetate might offer better assessment of recurrent prostate
      cancer than (18)F-2-fluoro-D-deoxyglucose-PET and monoclonal antibody imaging
      with the prostate specific membrane antigen antibody (111)In-capromab pendetide
      (ProstaScint). SUMMARY: With systemic therapies for recurrent prostate cancer
      after radical prostatectomy or radiation therapy being noncurative, the
      application of MRI and nuclear medicine modalities can help to identify patients
      who have isolated local recurrence amenable to salvage treatment.

PMID- 18090494
TI  - Multiparametric magnetic resonance imaging in prostate cancer: present and
      future.
AB  - PURPOSE OF REVIEW: The purpose of this article is to review the current status of
      advanced MRI techniques based on anatomic, metabolic and physiologic properties
      of prostate cancer with a focus on their impact in managing prostate cancer
      patients. RECENT FINDINGS: Prostate cancer can be identified based on reduced T2
      signal intensity on MRI, increased choline and decreased citrate and polyamines
      on magnetic resonance spectroscopic imaging (MRSI), decreased diffusivity on
      diffusion tensor imaging (DTI), and increased uptake on dynamic contrast enhanced
      (DCE) imaging. All can be obtained within a 60-min 3T magnetic resonance exam.
      Each complementary method has inherent advantages and disadvantages: T2 MRI has
      high sensitivity but poor specificity; magnetic resonance spectroscopic imaging
      has high specificity but poor sensitivity; diffusion tensor imaging has high
      spatial resolution, is the fastest, but sensitivity/specificity needs to be
      established; dynamic contrast enhanced imaging has high spatial resolution, but
      requires a gadolinium based contrast agent injection, and sensitivity/specificity
      needs to be established. SUMMARY: The best characterization of prostate cancer in
      individual patients will most likely result from a multiparametric
      (MRI/MRSI/DTI/DCE) exam using 3T magnetic resonance scanners but questions remain
      as to how to analyze and display this large amount of imaging data, and how to
      optimally combine the data for the most accurate assessment of prostate cancer.
      Histological correlations or clinical outcomes are required to determine
      sensitivity/specificity for each method and optimal combinations of these
      approaches.

PMID- 18090497
TI  - Bladder cancer: can imaging change patient management?
AB  - PURPOSE OF REVIEW: Recent technical advances have an impact on the management of
      patients with bladder cancer. RECENT FINDINGS: Intravenous pyelography has been
      largely replaced with multiphasic computed tomography urography performed on
      multislice computed tomography scanners. The new computed tomography technique
      allows direct and indirect detection of urothelial cancer throughout the
      urothelium and also identifies other causes of hemorrhage in patients presenting
      with hematuria. Thin-slice and multiplanar reconstructions have improved computed
      tomography staging of bladder cancer. In addition, computed tomography allows
      evaluation for lymphatic and distant metastases in a single examination. MRI
      continues to have a role in evaluating the depth of tumor invasion into the
      bladder wall but the assessment is difficult after transurethral resection of the
      bladder. SUMMARY: Multislice spiral computed tomography with a multiphase
      computed tomography urography protocol supplementing cystoscopy is currently
      considered the imaging modality of choice for examining patients with microscopic
      and gross hematuria. Computed tomography and MRI can visualize bladder cancer and
      perivesical infiltration, but MRI is superior for evaluation of the depth of
      invasion in the bladder wall.

PMID- 18090498
TI  - Functional imaging in penile cancer: PET/computed tomography, MRI, and sentinel
      lymph node biopsy.
AB  - PURPOSE OF REVIEW: The presence and extent of lymph node metastasis and primary
      tumor are among the most important prognostic factors in penile cancer. While
      inguinal lymphadenectomy is currently the most accurate means of staging, it is
      associated with severe morbidity and even mortality. Recent literature was
      reviewed for alternative means of staging. RECENT FINDINGS: Functional imaging
      modalities distinguish between inguinal lymph nodes with and without metastasis.
      The false-negative rate of dynamic sentinel lymph node biopsy has recently
      improved from approximately 20 to 5% in one study. In 13 patients with penile
      cancer, (18)F-fluorodeoxyglucose-PET/computed tomography was 80% sensitive and
      100% specific for lymph node metastasis, but missed micro-metastasis. In seven
      patients with penile cancer, MRI with lymphotrophic nanoparticles was 100%
      sensitive and 97% specific for lymph node metastasis. SUMMARY: Combined
      PET/computed tomography and sentinel lymph node biopsy may help to detect both
      inguinal micrometastasis and pelvic and abdominal metastasis. Since MRI is highly
      accurate for staging of both primary penile cancer and its lymph node metastasis,
      however, it may turn out to be a powerful tool for a one-stop modality in the
      staging of penile cancer.

PMID- 18090499
TI  - Recent advances in preoperative imaging of renal tumors.
AB  - PURPOSE OF REVIEW: The aim of this article is to discuss the expanded role of
      imaging and imaging-guided biopsy in the management of renal tumors. RECENT
      FINDINGS: Certain features on cross-sectional imaging aid in preoperative
      differentiation of renal parenchymal tumors. Volumetric measurement on imaging
      has demonstrated variable growth rate among renal tumors. Radioisotope labeled
      chimeric G250, a monoclonal antibody to carbonic anhydrase IX antigen, has shown
      the potential to target clear cell renal carcinoma with high sensitivity and
      specificity. With advances in technology, imaging-guided biopsy has shown higher
      accuracy and diagnostic rate than the past in the preoperative diagnosis of renal
      tumors. SUMMARY: Greater understanding of the imaging features of specific kinds
      of renal masses and more accurate imaging-guided biopsy are important advances in
      the management of renal tumors.

PMID- 18090500
TI  - Current and future imaging for urologic interventions.
AB  - PURPOSE OF REVIEW: This review focuses on novel imaging techniques used for
      guiding urologic procedures that are likely to provide additional opportunities
      to physicians in the years to come. RECENT FINDINGS: In the past, most image
      guided urologic procedures have utilized two-dimensional x-ray images. This
      review will discuss the use of a variety of new and more sophisticated image
      guiding tools such as rotational fluoroscopy, intraoperative ultrasound,
      endoscopic ultrasound, ultrasound elastography, real-time computed tomography,
      magnetic resonance fluoroscopy, and molecular imaging. SUMMARY: Technological
      breakthroughs in imaging have led to the development of minimally invasive
      techniques in urologic care. Application of these new techniques brings together
      the complementary disciplines of endourology and interventional radiology to
      optimize treatments and outcomes for urologic disease.

PMID- 18090501
TI  - Bibliography. Current world literature. Benign prostatic hyperplasia.

PMID- 18090502
TI  - The atypical antipsychotics olanzapine and risperidone in the treatment of
      posttraumatic stress disorder: a meta-analysis of randomized, double-blind,
      placebo-controlled clinical trials.
AB  - Posttraumatic stress disorder (PTSD) is a prevalent and disabling mental illness.
      Small studies found atypical antipsychotics (AAs) to be beneficial in the
      treatment of patients with PTSD regardless of psychotic symptoms who are
      unresponsive to conventional pharmacological treatments such as serotonin
      selective reuptake inhibitors. This study reports the results of a meta-analysis
      of existing randomized, double-blind, placebo-controlled clinical trials (RCTs)
      of AAs as a monotherapy or augmentation therapy for the treatment of patients
      with PTSD. Seven RCTs were identified through extensive scans of databases, which
      included PubMed, MedLine, the National PTSD Center Pilots database, PsycINFO,
      Cochrane Central Register of Controlled Trials, and the Abstracts Library of the
      American Psychiatric Association with predefined inclusion criteria. Dichotomous
      and continuous measures were performed using a fixed effects model, heterogeneity
      was assessed, and subgroup analyses were done. Data from seven RCTs involving a
      total of 192 PTSD patients (102 randomized to AAs and 90 randomized to placebo)
      were analyzed. The results show that AAs may have a beneficial effect in the
      treatment of PTSD, as indicated by the changes from baseline in Clinician
      Administered PTSD Scale total scores [standardized mean difference (SMD)=-0.45,
      95% confidence interval (CI) (-0.75, -0.14), P=0.004]. In addition, the overall
      SMD of the mean changes in the three Clinician Administered PTSD Scale subscores
      was statistically significant (P=0.007) between AAs and placebo groups, favoring
      AAs over placebo (SMD=-0.27, 95% CI=-0.47, -0.07). In particular, the symptom of
      'intrusion' was mainly responsible for this significance. Clinical significance
      of the results, however, should be carefully interpreted and translated into
      clinical practice, given that the quality and availability of currently existing
      RCTs included in the analysis.

PMID- 18090503
TI  - Priapism associated with atypical antipsychotic medications: a review.
AB  - Priapism defined as persistent, painful and prolonged penile erection, was
      previously thought to be associated only with the use of the older, conventional
      first generation or typical antipsychotic medications as well as some other
      medications, notably, trazodone. The mechanism of priapism associated with
      antipsychotics is not clear but is thought to be related to alpha-adrenergic
      blockage that is mediated by the alpha receptors in the corpora cavernosa of the
      penis. Atypical antipsychotics, also known as second-generation antipsychotics,
      owing to their favorable side effect profile, are being prescribed with
      increasing frequency and are not as frequently considered to cause priapism. Some
      case reports reporting this side effect with their use, however, are found.
      Pubmed and Ovid databases were searched to obtain all articles and case reports
      of antipsychotic drug-induced priapism. Key search words included 'priapism',
      'antipsychotics' and 'drug-induced priapism'. References of all identified
      studies were also reviewed. A total of 50 publications were obtained. Most of the
      atypical antipsychotics have been reported to cause priapism. These cases have
      occurred in patients shortly after having been started on the antipsychotic
      medications as well as in those who have been on them for an extended period of
      time without modification in dosage, and have also occurred sometimes, with the
      addition of another antipsychotic, lithium or serotonin-specific reuptake
      inhibitor. Priapism has been documented with nearly all the atypical
      antipsychotic medications. It is, however, a rarely reported side effect and
      therefore, underappreciated. Priapism can cause irreversible erectile dysfunction
      and is a urologic emergency. Clinicians should monitor patients on these
      medications for this rare, yet significant side effect. Furthermore, caution must
      be used when adding new drugs to the regimen and patients should be closely
      monitored for this side effect. Educating patients about the risk of developing
      priapism would help increase awareness of the side effect and promote early
      reporting thereby, decreasing long-term morbidity.

PMID- 18090504
TI  - Long-term efficacy of pregabalin in generalized anxiety disorder.
AB  - A multicenter, randomized, placebo-controlled, double-blind study was conducted
      to evaluate the efficacy of pregabalin in preventing relapse of generalized
      anxiety disorder (GAD) after response to short-term treatment. Outpatients
      (n=624) with GAD for > or =1 year received open-label pregabalin (450 mg/day) for
      8 weeks and, if a clinical response was observed, were randomized to receive
      either pregabalin (450 mg/day; n=168) or placebo (n=170) for 24 weeks. The
      primary efficacy parameter was time to relapse. Among responders to open-label
      acute treatment with pregabalin, time to relapse of GAD was significantly longer
      for patients treated with pregabalin compared with placebo (P<0.0001). Fifty per
      cent of the placebo group had relapsed by day 23, and at study endpoint, 65% had
      relapsed. In the pregabalin group, only 42% had relapsed by study end. Total
      attrition during double-blind treatment was somewhat higher on pregabalin
      compared with placebo (21.4 vs. 15.3%); attrition owing to adverse events (AEs)
      was also somewhat higher on pregabalin (6.0 vs. 2.4%). AEs were relatively low in
      the double-blind phase; only three AEs occurred with an incidence of more than 5%
      on pregabalin and placebo, respectively: infection (14.9 vs. 11.2%), headache
      (10.1 vs. 11.2%), and somnolence (6.0 vs. 0%). No safety concerns were identified
      with long-term treatment. The study indicates that pregabalin is an effective
      treatment for the prevention of relapse in patients with GAD.

PMID- 18090505
TI  - Clinical effect of nemifitide, a novel pentapeptide antidepressant, in the
      treatment of severely depressed refractory patients.
AB  - Clinical data were evaluated from an open-label, single-center, pilot study in
      patients with chronic refractory depression. The primary efficacy criterion was
      the change from baseline using the Montgomery-Asberg Depression Rating Scale. The
      secondary efficacy criteria were the 17-item Hamilton Depression Rating Scale and
      the Clinical Global Impression-Improvement scale. Response to treatment (40-240
      mg once per day by subcutaneous injection for 10-20 doses) was defined as more
      than 50% improvement in the Montgomery-Asberg Depression Rating Scale from
      baseline or Clinical Global Impression-Improvement < or =2 and lasting for at
      least two sequential weeks. Patients with a sustained response at the end point
      in the acute main treatment phase were enrolled for up to 2 years in a
      maintenance phase of the study to determine duration of response and to initiate
      retreatments upon relapse. Of the 25 patients with chronic refractory depression,
      11 patients showed a response for Montgomery-Asberg Depression Rating Scale and
      one responded according to the secondary criterion Hamilton Depression Rating
      Scale. In seven of the 11 responders to Montgomery-Asberg Depression Rating Scale
      the effects were sustained for the remainder of the acute phase. Two additional
      sustained responders identified according to secondary criteria (Hamilton
      Depression Rating Scale or Clinical Global Impression-Improvement) were also
      enrolled in the maintenance phase. All nine sustained responders were retreated,
      as needed, in the maintenance phase of the study, ranging from 71 to 660 days.
      Mean duration of response following initial treatment and between retreatments
      was around 2 months. Pharmacokinetic data indicated dose-proportional systemic
      exposure to the drug.

PMID- 18090506
TI  - Six-month compliance with antidepressant medication in the treatment of major
      depressive disorder.
AB  - The investigation of compliance in patients with major depressive disorder (in
      drop-outs versus completers and in first episode versus recurrent episode
      patients). A total of 85 outpatients with major depressive disorder were followed
      for 6 months. Different dimensions of compliance were investigated: drop-outs
      versus completers and their medication adherence (with electronic monitoring).
      General linear mixed models were applied to examine the time courses of
      adherence. Drop-out rates were higher in younger patients and in patients with a
      lower initial depression severity. The adherence during 6 months of treatment
      with selective serotonin reuptake inhibitors was above 80 in 70% of the patients.
      The adherence decreased by 2.5% per month and decreased more than three times
      more rapidly in drop-outs (from baseline to time of drop-out). A medical visit
      resulted in a temporary increase in pill intake. General linear mixed model
      analysis showed that the predicted outcome was worse in drop-outs than in
      completers and worse in recurrent episode patients than in first episode patients
      (the former showing a higher adherence). Adherence decreases with time during 6
      months of treatment with antidepressants and is influenced by demographic and
      clinical variables. Completers show a higher adherence than drop-outs. The
      outcome was worse in recurrent episode patients than first episode patients
      although they had a higher adherence.

PMID- 18090507
TI  - Escitalopram in the treatment of multisomatoform disorder: a double-blind,
      placebo-controlled trial.
AB  - Despite the prevalence of multisomatoform disorder (MSD), there are few
      controlled trials of its pharmacotherapy. The aim of this study was to compare
      the efficacy and safety of escitalopram (10-20 mg/day) with that of placebo in
      treating patients with MSD over a 12-week period. Fifty-one outpatients aged from
      18 to 65 years, with multiple medically unexplained symptoms, were recruited. The
      primary efficacy measure was a change on the Patient Health Questionnaire-15
      scores from baseline to endpoint. Secondary efficacy endpoints included the
      Clinical Global Impression-Improvement score, the psychic and somatic subscales
      of the Hamilton Anxiety Scale, Montgomery-Asberg Depression Rating Scale, the
      Visual Analogue Pain Rating Scale, the Scale for the Assessment of Illness
      Behaviour and the Sheehan Disability Scale. On the primary analysis of
      covariance, escitalopram-treated patients had significantly greater reductions in
      Patient Health Questionnaire scores (P<0.0001) compared with placebo at week 12.
      Significant separation from placebo occurred from week 6 onwards. Escitalopram
      was superior to placebo on all secondary outcome endpoints, with the exception of
      the Scale for the Assessment of Illness Behaviour. The medication was well
      tolerated. In conclusion, in this 12-week, randomized, placebo-controlled study,
      escitalopram (10-20 mg/day) was both effective and well tolerated in the
      treatment of patients with MSD. Compared with placebo, escitalopram was
      associated with lower symptom scores, increased response and remission rates, and
      improved functioning.

PMID- 18090508
TI  - High-dose escitalopram for the treatment of obsessive-compulsive disorder.
AB  - The aim of this study was to evaluate the efficacy and tolerability of high-dose
      escitalopram in patients suffering from obsessive-compulsive disorder (OCD). In
      an open-label, 16-week prospective study, patients with OCD received escitalopram
      at a dose of 20 mg/day for 3 weeks, after a 1-week titration at 10 mg/day.
      Patients who did not achieve a > or =25% reduction from baseline in the Yale
      Brown Obsessive Compulsive Scale (Y-BOCS) score during these 4 weeks were
      continued on higher doses of escitalopram (maximum 50 mg/day) for 12 weeks. The
      primary efficacy measure of OCD symptoms was change from baseline in the Y-BOCS
      score. Overall, 67 patients (33 women, 34 men) with a mean Y-BOCS score of 29.6
      entered the study. After 4 weeks of standard-dose escitalopram treatment, one
      patient discontinued owing to pregnancy, and two patients achieved a reduction in
      Y-BOCS > or =25%. Consequently, 64 patients were eligible to receive high-dose
      escitalopram (mean dose, 33.8 mg/day at endpoint). At endpoint, high-dose
      escitalopram had significantly improved the OCD symptoms (Y-BOCS score) and all
      the other efficacy measures (P<0.001), compared with baseline. Escitalopram was
      also well tolerated, with no discontinuations during the 12-week high-dose phase.
      The only reported adverse drug reactions were dry mouth (n=8, 12.1%) and
      decreased sexual desire (n=21, 31.8%). Preliminary investigation shows that high
      dose escitalopram is an efficacious and well tolerated treatment for patients
      suffering from severe OCD. Randomized, blinded studies are needed to reinforce
      these findings.

PMID- 18090509
TI  - Increased rate of treatment with antidepressants in patients with multiple
      sclerosis.
AB  - The prevalence of depression and anxiety is increased in patients with multiple
      sclerosis, but it has not been investigated whether these conditions are treated
      in clinical practice. The objective of this study was to investigate whether the
      rate of treatment with antidepressants is increased in patients with multiple
      sclerosis compared with patients with other chronic illnesses and compared with
      the general population. By linkage of nationwide case registers, all patients
      were identified, who had received a main diagnosis of multiple sclerosis or
      osteoarthritis at first admission or during outpatient contact in the period 1995
      2000 in Denmark. Rates of subsequent purchase of antidepressants for these
      patients were calculated. In total, 417 patients with a main diagnosis of
      multiple sclerosis and 12 127 patients with a main diagnosis of osteoarthritis,
      at first discharge from hospital or outpatient contact, were included. Patients
      with a diagnosis of multiple sclerosis had a 3.21 [95% confidence intervals (CI):
      2.56-4.03] times increased rate of subsequently purchasing antidepressants
      compared with patients with a first diagnosis of osteoarthritis, and a 4.75 times
      (95% CI: 3.91-5.76) increased rate when compared with the rate among a gender
      matched, age-matched, and calendar-matched sample of the general population. The
      rates were increased in all subgroups of patients regardless of gender, age,
      socioeconomic group, and time elapsed since diagnosis.

PMID- 18090510
TI  - Cs of change in the C-suite.
AB  - This bimonthly department, sponsored by the American Organization of Nurse
      Executive (AONE), presents information to assist nurse leaders in shaping the
      future of healthcare through creative and innovative leadership. The strategic
      priorities of AONE anchor the editorial content. They reflect contemporary
      healthcare and nursing practice issues that challenge nurse executives as they
      strive to meet the needs of patients.

PMID- 18090512
TI  - Leadership roles for nurses in healthcare design.
AB  - Nearly $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 author discusses roles in healthcare design that nurse leaders can assume to
      ensure a successful project.

PMID- 18090513
TI  - Politically engaging. Interview by Karen S Hill.
AB  - This department highlights nursing leaders who have demonstrated the ability to
      inspire and lead change. This competency is seen in the ability to create,
      structure, and implement organizational change through strategic vision, risk
      taking, and effective communication. Each article showcases a project of a nurse
      leader who demonstrates change in a variety of environments ranging from acute
      care hospitals to home care and alternative practice settings. Included are
      several "lessons learned" applicable to multiple settings that provide insight
      for other nurses in executive practice.

PMID- 18090514
TI  - Organizing: new ways to harness complexity.
AB  - As systems evolve, their natural tendency is to become increasingly more complex.
      Studies in the field of complex systems have generated new perspectives on
      managing in social organizations such as hospitals. Much of this research appears
      as a natural extension of the cross-disciplinary field of systems theory. This is
      the second in a 5-part series on applying complex systems science to the
      traditional management concepts of planning, organizing, directing, coordinating,
      and controlling. In this article, the concept of organizing is explored from a
      complex systems perspective.

PMID- 18090515
TI  - Height of hospital beds and inpatient falls: a threat to patient safety.

PMID- 18090516
TI  - Transforming a hospital nursing research fellowship into an evidence-based
      practice fellowship.
AB  - An established hospital-based nursing research fellowship program was transformed
      into an evidence-based practice fellowship despite its previous high satisfaction
      ratings from nursing leaders and nurse fellow participants. The faculty for the
      fellowship program determined that the long-term outcomes of the research program
      were insufficient in light of the hospital resources committed to the fellowship
      program. An evidence-based practice approach was then created in anticipation
      that greater short-term and more sustained longer-term benefits for the hospital
      would be realized. The transformation of the fellowship and the short-term
      outcomes are described.

PMID- 18090517
TI  - Using the Quality-Caring Model to organize patient care delivery.
AB  - The organization of patient care in many acute care institutions lacks a
      foundation in nursing theory, yet preliminary evidence of the value of
      professional nursing care is increasing. The process and preliminary benefits of
      organizing patient care according to a professional practice model are presented
      using a collaborative partnership between an acute care organization and a school
      of nursing. A pilot implementation plan with formative and summative evaluation
      provided preliminary evidence used in project expansion.

PMID- 18090518
TI  - Organizational change strategies for evidence-based practice.
AB  - Evidence-based practice, a crucial competency for healthcare providers and a
      basic force in Magnet hospitals, results in better patient outcomes. The authors
      describe the strategic approach to support the maturation of The Johns Hopkins
      Nursing evidence-based practice model through providing leadership, setting
      expectations, establishing structure, building skills, and allocating human and
      material resources as well as incorporating the model and tools into
      undergraduate and graduate education at the affiliated university.

PMID- 18090519
TI  - Achieving quality and fiscal outcomes in patient care: the clinical mentor care
      delivery model.
AB  - Contemporary patient care requires sophisticated clinical judgment and reasoning
      in all nurses. However, the level of development regarding these abilities varies
      within a staff. Traditional care models lack the structure and process to close
      the expertise gap creating potential patient safety risks. In an innovative
      model, senior, experienced nurses were relieved of direct patient care
      assignments to oversee nursing care delivery. Evaluation of the model showed
      significant impact on quality and fiscal outcomes.

PMID- 18090520
TI  - Developing leaders at every level: accountability and empowerment actualized
      through shared governance.
AB  - The shortage of frontline nursing staff and their managers in acute care
      organizations necessitates strategies to both use and recognize the unique
      knowledge and skills of these individuals. The authors describe one
      organization's successful implementation of a shared decision-making structure
      that promotes an empowering work environment in which professional fulfillment
      and personal satisfaction can flourish. With support and opportunity, leaders are
      developed across all levels of nursing.

PMID- 18090521
TI  - The clinical significance of EEG cyclic alternating pattern during coma.
AB  - To define the clinical significance of EEG "cyclic alternating pattern" (ECAP).
      ECAP is the periodic presence of a high-voltage slow waves alternating with low
      voltage irregular faster activity. This term was first described in comatose
      patients in 1944. It has been less recognized and may be underreported since
      then. The clinical significance of ECAP in the state of coma remains unknown. We
      reviewed our prospective EEG database for consecutive patients studied over a
      period of 4 years (n = 4,819) looking for patterns consistent with ECAP. We
      reviewed the charts of the patients with the above EEG pattern to define the
      clinical setting and the eventual outcome. Eleven patients were identified. All
      patients identified were found to be in the coma state at the time of the EEG.
      The majority of patients (n = 10) survived the coma, and half returned to the
      community in good functional status. ECAP is seen rarely in comatose patients.
      Regardless of the cause of the coma, the presence of ECAP carries an overall good
      prognosis for both survival and recovery.

PMID- 18090522
TI  - Video-EEG monitoring in a geriatric veteran population.
AB  - Video-EEG monitoring is a standard tool to evaluate possible seizures. However,
      there are limited data available for the elderly population, and no data are
      available for the elderly veteran population. The records of 71 veterans ages 60
      and older who underwent video-EEG monitoring at the Michael E. DeBakey Veterans
      Affairs Medical Center from 1999 to 2006 were reviewed. The average age was 68
      years, and 94% were male. Typical events occurred in 34 of 71 patients (48%).
      Twelve patients (35%) had epileptic seizures; most were temporal lobe seizures
      (75%). The remaining 22 patients (65%) had a nonepileptic event. Of these, 10
      (45%) had psychogenic nonepileptic seizures and 12 (55%) had other physiologic
      nonepileptic events. AEDs were previously prescribed in 14 of the 22 nonepileptic
      patients (64%). In our study, most events were nonepileptic, partly reflecting
      the unique nature of the VA population. There was a slightly higher number of
      physiologic nonepileptic events; however, psychogenic seizures are also
      frequently seen. Most of the patients with nonepileptic events were previously
      treated with AEDs. Most of the epileptic events captured were temporal lobe
      seizures. Video-EEG monitoring in the elderly is useful in the characterization
      of paroxysmal events.

PMID- 18090523
TI  - EEG findings in the persistent vegetative state.
AB  - The definition of the persistent vegetative state (PVS) is relatively
      straightforward, but its diagnosis can be challenging. We reviewed a series of
      EEG performed in patients with PVS to assess the diagnostic value of EEG. We
      reviewed records of all hospital patients with a diagnosis of persistent
      vegetative PVS. EEG findings included normal, continuous generalized slowing,
      intermittent generalized slowing, background slowing, background suppression,
      alpha, generalized periodic pattern, PLEDS, and triphasic waves. EEG findings had
      no association with etiology and varied from one pattern to another in the same
      patients' EEGs obtained at different times (see table). We conclude that EEG
      findings in PVS are heterogeneous and too variable to be of diagnostic value.

PMID- 18090524
TI  - False lateralization of electrographic onset in the setting of cerebral atrophy.
AB  - The localization of seizure onset relies on the concordance of clinical,
      electrographic, and imaging data, often supplemented by corroborating functional
      studies. On occasion, the presurgical evaluation may yield discordant
      information. Although the localization of seizure onset is sometimes in doubt, it
      is rare that the lateralization of the focus is in question. To date, there has
      been only a single publication on falsely lateralizing ictal EEG onsets in the
      setting of atrophic lesions. We describe two patients in whom the ictal EEG
      suggested seizure onset from the hemisphere opposite to the one with a sizeable
      atrophic lesion. The first patient was operated on without invasive EEG testing.
      In the second patient, we decided to place subdural electrodes before resection.
      In each case, resection of the lesion resulted in improvement of intractable
      seizures.

PMID- 18090525
TI  - The fourth dorsal interosseus pedis muscle: a useful muscle in routine
      electromyography.
AB  - The aim of the study was to assess the utility of needle examination of the
      fourth dorsal interosseus pedis (FDIP) muscle in routine EMG. FDIP is an easily
      accessible muscle and may be less prone to blunt trauma as compared with the
      other foot muscles but despite its potential utility in electrophysiology, little
      if any data are available on the FDIP muscle. Detailed neurologic examination,
      nerve conduction, and needle EMG studies were performed in 118 individuals
      referred to the EMG laboratory of a tertiary referral center. The FDIP was
      studied by inserting a needle obliquely at an angle of about 30 degrees
      immediately proximal to the fourth and fifth metatarsal heads. In 44 subjects
      (patients/volunteers) with normal studies, <5% had increased insertional activity
      (IA) in the FDIP, but none had sustained spontaneous activity (SA). Among 32
      patients with mixed sensorimotor polyneuropathy, FDIP showed abnormal SA in >90%.
      In patients with S1 root compromise, 66% had sustained SA in FDIP but none with
      involvement of L3, L4, or L5 nerve root alone. Two of the four patients with
      tibial and one of five with peroneal neuropathies had increased SA in this
      muscle; none with other lower limb focal neuropathies. In patients with
      lumbosacral plexopathy, FDIP showed denervation potentials with diffuse plexus
      involvement but not with upper plexopathy. Almost all patients tolerated the FDIP
      needle examination well. End plates were frequently encountered in the FDIP
      muscle. We concluded that in normal feet, the FDIP muscle has a low incidence of
      sustained SA. Abnormal SA in FDIP correlates well with the overall neurologic
      condition, and it may be a useful muscle to include in routine electrodiagnostic
      evaluation.

PMID- 18090526
TI  - Supratentorial ischemic stroke: more than an upper motor neuron disorder.
AB  - The primary goal of this study was to identify secondary functional changes in
      the peripheral motor units of the paretic upper extremity (UE) in patients with
      severe ischemic stroke and to determine how these changes develop during the
      first weeks after stroke. An inception cohort of 27 consecutive patients with an
      acute ischemic supratentorial stroke and an initial UE paralysis was compared
      with 10 healthy control subjects. The ulnar nerve was electrically stimulated
      proximal to the wrist and electromyographic recordings were obtained from the
      abductor digiti minimi muscle. Hemiparetic side mean values of the compound
      muscle action potential (CMAP) 1 and 3 weeks after stroke were compared with the
      nonparetic side and with CMAP values obtained from healthy control subjects. The
      mean CMAP amplitude in patients was significantly lower on the paretic side
      compared with the nonparetic side and with control subjects. Decrease in CMAP
      amplitude was observed in more than half of the stroke patients, sometimes as
      early as 4 days after stroke, and persisted in most cases. Whenever present, it
      was accompanied by absence of motor recovery at that specific time after stroke.
      Decreased CMAP amplitude in the abductor digiti minimi muscle can be seen already
      in the very acute phases after stroke unrelated to peripheral neuropathy,
      radiculopathy, or plexopathy, and it is accompanied by absence of UMN recovery.
      This knowledge is important for interpreting electrophysiological data in stroke
      patients.

PMID- 18090527
TI  - Influence of cabergoline on motor excitability in patients with restless legs
      syndrome.
AB  - To investigate whether the increased urge to move the legs in restless legs
      syndrome (RLS) corresponds to an electrophysiological phenomenon and whether
      motor excitability or behavior is influenced by the treatment with a dopamine
      agonist. We examined 10 patients who had RLS with transcranial magnetic
      stimulation (TMS) before and during treatment with the dopamine agonist
      cabergoline. Results were compared with data obtained from healthy subjects.
      Inhibitory mechanisms were explored by measurement of the cortical silent period
      (cSP). Recordings were obtained from the right anterior tibial muscle. Clinical
      severity of RLS was rated using the International Restless Legs Syndrome Study
      Group Rating Scale (IRLSSGRS). During therapy with cabergoline, all patients
      reported a significant improvement of RLS symptoms. Before medication, patients
      showed a significant shortening of cSP compared with healthy subjects. After 14
      days of treatment with cabergoline, cSP normalized in RLS patients; 90 days after
      the start of daily cabergoline, cSP tended to shorten again, whereas RLS symptoms
      further improved. There was no correlation between cSP duration and IRLSSGRS
      results. There were no differences in patient and control motor thresholds. These
      thresholds remained unchanged during treatment with cabergoline. RLS patients
      have a disturbance of inhibitory neurons that can temporarily be reversed with a
      dopamine agonist. However, the cSP does not correlate with the clinical symptoms.

PMID- 18090530
TI  - Editing a scientific journal: problems and challenges.

PMID- 18090531
TI  - Arterial transfer functions and the reconstruction of central aortic waveforms:
      myths, controversies and misconceptions.
AB  - Continuing reports in the literature regarding the potential of central pulse
      wave analysis in clinical practice and a recent consensus statement demonstrate
      the increasing interest in the clinical application of arterial transfer
      functions. A number of misconceptions, however, persist regarding their use. In
      spite of ongoing controversy, there are considerable published data that would
      permit users to assess the validity and accuracy of the technique. We provide a
      comprehensive review of available data, all of which appear to be clear and
      consistent. The technique does not permit accurate reconstruction of central
      waveforms from entirely non-invasively acquired data. We should move on from the
      misconception that what is being studied is central aortic data when transfer
      functions are applied non-invasively, and accept that it is radial waveform data
      that have been passed through a single mathematical transformation. We have a
      readily applicable, non-invasive and reproducible technique for acquiring radial
      waveform data, with or without the application of a generalized arterial transfer
      function. We must explore the potential of this technique in an analytical
      manner, and without untenable preconceptions, if we are to learn the secrets that
      it may yet reveal.

PMID- 18090532
TI  - Arterial transfer functions: background, applications and reservations.

PMID- 18090533
TI  - Measurement of C-reactive protein and natriuretic peptides for cardiovascular
      risk assessment: the need for age and gender-specific thresholds.

PMID- 18090535
TI  - Central blood pressure as estimate of cardiovascular risk: potentials and
      limitations.

PMID- 18090534
TI  - Prorenin and glomerulosclerosis?

PMID- 18090536
TI  - Association of heart rate with microalbuminuria in cardiovascular risk patients:
      data from I-SEARCH.
AB  - BACKGROUND: Microalbuminuria (MAU) is an indicator of impaired renal function and
      a relevant risk predictor for cardiovascular events. An increased heart rate is
      closely correlated with increased cardiovascular mortality. The International
      Survey Evaluating Microalbuminuria Routinely by Cardiologists in Patients with
      Hypertension (I-SEARCH) investigated 21 050 patients with hypertension and risk
      factors for cardiovascular disease. In patients in sinus rhythm (n = 18 900) the
      relationship between increased heart rate and the prevalence of MAU was analysed.
      METHODS AND RESULTS: The study was performed in 26 countries worldwide from
      September 2005 to March 2006. Heart rate, blood pressure, urine albumin and serum
      creatinine were measured as key parameters. With increasing heart rate (> 80 bpm
      to < 120 bpm) the proportion of patients with MAU increased from 63 to 69% (P <
      0.0001). The odds ratio (OR) for MAU increased with increasing heart rate [heart
      rate 80-100 bpm compared with 60 bpm: OR, 1.47; 95% confidence interval (CI),
      1.29-1.68; P < 0.0001; and heart rate 100-120 bpm compared with 60 bpm: OR, 1.56;
      95% CI, 1.22-1.99; P = 0.0004]. The prevalence of MAU was similar whether or not
      patients were receiving beta-blockers; but MAU was significantly reduced in
      physically active patients compared with sedentary patients (OR, 0.78; 95% CI,
      0.73-0.84; P < 0.0001). SUMMARY: These results show that heart rate is an
      independent predictor for the prevalence of MAU in hypertensive patients with
      cardiovascular risk factors. In contrast to beta-blocker therapy, physical
      activity markedly decreased MAU with increasing heart rates. Further controlled
      and prospective studies are needed to show that lowered heart rates in
      combination with MAU can significantly reduce kidney damage, as well as
      cardiovascular events.

PMID- 18090537
TI  - Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and
      high sensitivity C-reactive protein is affected by age and sex.
AB  - BACKGROUND: Previous studies have shown that the urine albumin/creatinine ratio
      (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain
      natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general
      population aged 41, 51, 61 or 71 years. This study investigated the impact of age
      and sex on their prognostic performance in a subgroup of 1994 apparently healthy
      individuals without diabetes, previous stroke or myocardial infarction, who did
      not receive any cardiovascular, antidiabetic or lipid-lowering medication.
      METHODS: In 1993-1994 we recorded cardiovascular risk factors, UACR, hsCRP and Nt
      proBNP. The composite cardiovascular endpoint (CEP) of cardiovascular death and
      non-fatal stroke or myocardial infarction was assessed after 9.5 years. RESULTS:
      In Cox regression analyses predicting CEP, the effects of log(hsCRP) and log(Nt
      proBNP) were modulated by sex (P < 0.05) and age (P < 0.05), respectively. The
      effect of logUACR was not significantly modulated by age or sex. Log(hsCRP)/SD
      did not predict CEP in women, but did predict CEP in 41 plus 51-year-old men
      [hazard ratio (HR) 1.71; 95% confidence interval, 1.1-2.6; P < 0.05] and 61 plus
      71-year-old men (HR 1.64; 1.3-2.2; P < 0.001). Log(Nt-proBNP)/SD predicted CEP in
      61 plus 71-year-old women (HR 1.74; 1.2-2.5; P < 0.01) and in 61 plus 71-year-old
      men (HR 1.58; 1.3-2.0; P < 0.001). CONCLUSION: Elevated hsCRP, reflecting early
      atherosclerosis, predicted CEP even in 41 plus 51-year-old men. Elevated Nt
      proBNP, reflecting subclinical cardiovascular damage, predicted CEP in 61 plus 71
      year-old subjects. Elevated UACR, reflecting endothelial dysfunction as well as
      microvascular damage, predicted events independently of age and sex, but
      primarily in 61 plus 71-year-old subjects.

PMID- 18090538
TI  - Automatic blood pressure measurement: the oscillometric waveform shape is a
      potential contributor to differences between oscillometric and auscultatory
      pressure measurements.
AB  - OBJECTIVE: To explore the differences between oscillometric and auscultatory
      measurements. METHOD: From a simulator evaluation of a non-invasive blood
      pressure (NIBP) device regenerating 242 oscillometric blood pressure waveforms
      from 124 subjects, 10 waveforms were selected based on the differences between
      the NIBP (oscillometric) and auscultatory pressure measurements. Two waveforms
      were selected for each of five criteria: systolic over and underestimation;
      diastolic over and underestimation; and close agreement for both systolic and
      diastolic pressures. The 10 waveforms were presented to seven different devices
      and the oscillometric-auscultatory pressure differences were compared between
      devices and with the oscillometric waveform shapes. RESULTS: Consistent patterns
      of waveform-dependent over and underestimation of systolic and diastolic
      pressures were shown for all seven devices. The mean and standard deviation, for
      all devices, of oscillometric-auscultatory pressure differences were: for the
      systolic overestimated waveforms, 36 +/- 28/-6 +/- 3 and 23 +/- 2/-1 +/- 3 mmHg
      (systolic/diastolic differences); for systolic underestimated waveforms, -21 +/-
      5/-4 +/- 3 and -11 +/- 4/-3 +/- 3 mmHg; for diastolic overestimated waveforms, 3
      +/- 4/12 +/- 5 and 17 +/- 6/10 +/- 2 mmHg; for diastolic underestimated
      waveforms, 1 +/- 4/-22 +/- 4 and -9 +/- 6/-29 +/- 4 mmHg; and for the two
      waveforms with good agreement, 0 +/- 6/0 +/- 3 and -2 +/- 4/-4 +/- 3 mmHg.
      Waveforms for which devices showed good oscillometric and auscultatory agreement
      had smooth envelopes with clearly defined peaks, compared with the broader
      plateau and complex shapes of those waveforms for which devices over or
      underestimated pressures. CONCLUSION: By increasing the understanding of the
      characteristics and limitations of the oscillometric method and the effects of
      waveform shape on pressure measurements, simulator evaluation should lead to
      improvements in NIBP devices.

PMID- 18090540
TI  - Urocortin 1 exhibits potent inhibition of cardiac sympathetic nerve activity in
      conscious sheep.
AB  - OBJECTIVES: Urocortin 1 (Ucn1) and the sympathetic nervous system both
      participate in cardiac and circulatory regulation, but little is known about
      their possible interactions. METHODS: We report the effects of Ucn1 on the
      cardiac sympathetic nerve activity (CSNA), haemodynamics and plasma
      catecholamines in normal sheep. RESULTS: Bolus intravenous administration of Ucn1
      at 2.5 and 10 microg in seven sheep had no significant effect on haemodynamic
      parameters, including heart rate, mean arterial pressure (MAP) and cardiac
      output. At these doses, however, Ucn1 administration reduced CSNA, with burst
      frequency (P = 0.011), burst incidence (P = 0.015) and burst area (P = 0.012) all
      significantly reduced in a dose-related manner compared with a time-matched
      control. At higher doses (25 and 100 microg; n = 5 sheep), Ucn1 induced
      significant rises in heart rate (P < 0.001) and cardiac output (P = 0.03) and
      reduced peripheral resistance (P = 0.03), but had no effect on MAP. Ucn1
      administration at the higher doses reduced CSNA, with burst incidence (P <
      0.001), burst area/min (P = 0.001) and burst area/100 beats (P < 0.001) all
      significantly reduced in a dose-related manner compared with a time-matched
      control. There was no change in plasma catecholamines at any dose. CONCLUSION:
      The present study shows that Ucn1 induces potent inhibition of sympathetic
      traffic to the heart at doses both above and below the threshold for direct
      actions of Ucn1 on the myocardium. These findings suggest an important role for
      Ucn1 in cardiovascular homeostasis and warrant further investigation for
      potential therapeutic applications in acute myocardial injury and heart disease.

PMID- 18090539
TI  - A long-term moderate magnesium-deficient diet aggravates cardiovascular risks
      associated with aging and increases mortality in rats.
AB  - OBJECTIVE: The present study aimed to show whether long-term moderate magnesium
      (Mg)-deficient (150 mg/kg) and Mg-supplemented (3200 mg/kg) diets (versus control
      diet: 800 mg/kg), modified the occurrence of cardiovascular risk induced by aging
      in the rat. METHODS: Cardiovascular and arterial functions were determined by a
      systemic hemodynamic study and by ex vivo measurements of vasoconstriction and
      endothelium dependent-vasorelaxation. Arterial wall structure was determined
      using pressure myograph chamber and histomorphometric methods. RESULTS: The main
      changes observed in old rats (96 weeks old) fed a control diet, in comparison to
      adult rats (16 weeks old) were increased pulse pressure, a loss of aortic
      endothelium-dependent relaxation, increased aortic wall thickness and a decrease
      of the aortic wall elastin/collagen ratio. Long-term moderate Mg deficiency
      progressively increased systolic blood pressure. Intra-arterial pulse pressure
      was higher in Mg-deficient old rats than in age-matched control rats.
      Histological examination showed that Mg deficiency increased the age-induced
      deleterious effects on composition and structure of aorta (media thickness,
      increased collagen content and reduction in the elastin/collagen ratio), which
      lead to large artery rigidity. Hypertension and increased pulse pressure may have
      contributed to the increase in the mortality rate observed in the hypertensive Mg
      deficient group. Although the long-term Mg-supplemented diet lowered blood
      pressure and decreased the mortality rate, it had no significant effect on aortic
      wall thickening and stiffening. CONCLUSION: It is suggested that a long-term and
      moderate Mg-deficient diet increases age-induced arterial thickness and stiffness
      in rats, and thus increases the cardiovascular risks incurred by aging.

PMID- 18090541
TI  - Adrenomedullary catecholamine, pressor and chronotropic responses to human
      coagulation beta-FXIIa mediated by endogenous kinins.
AB  - OBJECTIVES: There is increasing evidence that blood coagulation factors can
      influence blood pressure. In the present study, we tested the hypothesis that the
      beta fragment of human coagulation factor XIIa (beta-FXIIa) induces adrenal
      catecholamine-mediated pressor and chronotropic responses via bradykinin
      generated from the plasma kallikrein-kinin system. METHODS AND RESULTS: In
      anaesthetized bioassay rats with blocked autonomic reflexes, in the Brown Norway
      strain a bolus injection of beta-FXIIa (1 microg/kg, administered intravenously)
      elicited a 170-fold rise in plasma epinephrine (from 0.12 +/- 0.02 to 20.58 +/-
      2.42 nmol/l; P < 0.001) and a fivefold increase in plasma norepinephrine (from
      0.11 +/- 0.02 to 0.57 +/- 0.09 nmol/l; P < 0.01), concurrent increases in
      systolic blood pressure (from 70 +/- 5 to 101 +/- 4 mmHg; P < 0.01) and heart
      rate (from 315 +/- 11 to 408 +/- 15 bpm; P < 0.01), and a doubling of bradykinin
      concentrations (P < 0.05). Bilateral adrenal medullectomy abolished both the
      catecholamine and the haemodynamic responses to beta-FXIIa. Catecholamine,
      bradykinin and haemodynamic responses to beta-FXIIa were absent in plasma
      kininogen-deficient Brown Norway Katholiek (BNK) rats. Exogenous bradykinin dose
      dependently reproduced these catecholamine and haemodynamic responses in Brown
      Norway and BNK rats, but not in Brown Norway adrenal medullectomized rats.
      CONCLUSION: The pressor and chronotropic responses to beta-FXIIa in this bioassay
      preparation are mediated exclusively through adrenal catecholamine release, and
      require plasma kininogens for their full expression. These observations suggest
      that interaction between the coagulation, kallikrein-kinin and sympatho-adrenal
      systems can exert important pressor effects in the absence of counterregulatory
      autonomic reflexes.

PMID- 18090542
TI  - Heart rate as a sympathetic marker during acute adrenergic challenge.
AB  - OBJECTIVE: Previous studies have shown that heart rate has a limited value in
      reflecting the chronic state of adrenergic overdrive characterizing several
      cardiovascular diseases. Whether this also applies to the ability of heart rate
      to reflect acute and generalized changes in sympathetic activity is unknown.
      METHODS: In 20 healthy young subjects (age: 25.2 +/- 1.2 years, mean +/- SEM) we
      measured beat-to-beat blood pressure (Finapres), heart rate (HR, ECG), venous
      plasma norepinephrine (NE, high-performance liquid chromatography) and efferent
      postganglionic muscle sympathetic nerve traffic (MSNA, microneurography) at rest
      and during a cold pressor test and two intravenous infusions of nitroprusside at
      increasing doses. RESULTS: Both cold pressor test and nitroprusside infusions
      triggered marked and significant increases in HR, plasma NE and MSNA; blood
      pressure showing an increase with cold pressor test and a reduction with
      nitroprusside. The magnitude of the responses was greater with the higher than
      with the lower dose of nitroprusside. The HR changes induced by cold pressor test
      were not significantly related to the concomitant NE and MSNA changes (r = -0.08
      and r = -0.18, P = NS). This was also the case for the lower and the higher dose
      of nitroprusside (NE: r = -0.11 and r = 0.08; MSNA: r = 0.01 and r = -0.11, P =
      NS for all). In contrast NE and MSNA changes induced by cold pressor test and by
      the lower and the higher dose of nitroprusside were significantly related to each
      other (r = 0.70, r = 0.89 and r = 0.79 respectively, P < 0.01 for all).
      CONCLUSIONS: In a given individual, HR responses to sympathetic challenge do not
      quantitatively reflect the degree of acute and generalized adrenergic activation.
      Qualitative information on the acute adrenergic effects of given stimuli should
      thus be based on the assessment of NE and MSNA rather than on HR changes.

PMID- 18090543
TI  - Influence of non-invasive measurements of arterial blood pressure in frequency
      and time-domain estimates of cardiac baroreflex sensitivity.
AB  - OBJECTIVE: To compare estimates of cardiac baroreceptor sensitivity (BRS)
      obtained by the Finapres device and from the direct measurement of arterial blood
      pressure (ABP) values from the ascending aorta, using both spectral analysis and
      sequence analysis. DESIGN: A cohort study of 45 coronary artery disease patients
      undergoing routine percutaneous coronary procedures. METHODS: Continuous supine
      recordings of resting ABP in the finger (Finapres), ascending aorta (Millar
      catheter-tip transducer) and electrocardiogram were obtained. Beat-to-beat values
      of systolic ABP (Finapres and aortic) and R-R interval were used to estimate the
      cardiac BRS from spontaneous sequences and by spectral analysis, using the alpha
      index for the low-frequency band (0.05-0.15 Hz). The influence of beta-blockers
      on BRS estimates was also investigated. RESULTS: No significant difference was
      observed between estimates of BRS derived from the Finapres (BRSFIN) and aortic
      ABP (BRSAO) by the spectral analysis method (Finapres bias 0.30 +/- 2.52
      ms/mmHg). For sequence analysis, BRSFIN was significantly higher than BRSAO (7.80
      +/- 4.52 versus 6.44 +/- 3.46 ms/mmHg), but the bias (1.36 +/- 3.10 ms/mmHg) was
      not significantly different from spectral analysis. No significant differences in
      BRS were found between beta-blocker users (n = 24) and non-users (n = 10) for
      either the processing method or source of ABP recording. CONCLUSION: Spectral
      analysis of cardiac BRS showed a better agreement between estimates obtained from
      the Finapres and aortic ABP.

PMID- 18090544
TI  - Augmentation of nitric oxide is crucial for the time-dependent effects of
      rosiglitazone on blood pressure and baroreflex function in rats.
AB  - OBJECTIVES: To determine the time-dependent effects of rosiglitazone (RSG) on
      blood pressure (MAP) and baroreflex sensitivity (BRS) and the involvement of
      nitric oxide (NO) in these effects. METHODS: Male Sprague-Dawley rats were
      treated with RSG (8 mg/kg per day, orally) or saline for 4, 8 and 12 weeks. BRS
      was determined by linear regression method with bolus injections of phenylephrine
      (PE-BRS) or sodium nitroprusside (NP-BRS). Insulin sensitivity (M value) was
      determined by euglycemic hyperinsulinemic clamp study. Vascular and cardiac
      responsiveness to isoproterenol, acetylcholine and NP were determined after
      ganglionic blockade. Effects of endogenous NO were examined by Nomega-nitro-L
      arginine-methyl ester (L-NAME) administration. RESULTS: RSG treatment time
      dependently decreased circulating lipids, insulin, glucose levels and insulin
      resistance (HOMA-IR) but increased plasma NOx levels. M values were progressively
      decreased in control rats, but remained unchanged in RSG-treated rats. Chronic
      RSG treatment progressively lowered MAP but reciprocally increased heart rate
      (HR). In addition, chronic RSG treatment significantly attenuated HR changes to
      methylatropine but enhanced HR changes to propranolol. Twelve-week RSG treatment
      enhanced PE-BRS which was suppressed by methylatropine but not propranolol, and
      attenuated NP-BRS which was sustained after methylatropine or propranolol.
      Moreover, 12-week RSG treatment also diminished cardiac responsiveness to
      isoproterenol and augmented vascular responsiveness to acetylcholine, but not to
      NP. L-NAME eliminated the differences in MAP and HR between groups, and reversed
      both RSG-induced enhanced PE-BRS and attenuated NP-BRS. Plasma NOx levels were
      highly correlated with RSG-mediated changes in the baseline MAP, HR and BRS.
      CONCLUSION: These data suggest that RSG-induced NO production is important for
      the time-dependent effects of RSG on MAP and BRS in rats.

PMID- 18090545
TI  - Kallikrein gene 'knock-down' by small interfering RNA transfection induces a
      profibrotic phenotype in rat mesangial cells.
AB  - BACKGROUND: Emerging evidence suggests that kallikrein exerts renoprotective
      effects independent of its haemodynamic actions. The aim of the current
      investigation was to delineate the role of kallikrein in the regulation of
      fibrosis, by 'knocking down' its expression using specific small interfering RNAs
      (siRNA). METHODS: Rat mesangial cells were treated with 12, 60, 120 nmol/l
      kallikrein-specific siRNAs. The consequent cellular genotypes and phenotypes were
      analysed. RESULTS: Western blotting demonstrated that mesangial cells produced a
      kallikrein protein, which was of a different molecular weight to urinary
      kallikrein from rats of the same species. Treatment of cells with siRNA resulted
      in a dose-dependent decrease in kallikrein mRNA levels, which impacted on other
      components of the kallikrein-kinin system, dose-dependently reducing bradykinin
      B2 receptor mRNA expression. Kallikrein suppression resulted in significant
      increases in fibronectin and transforming growth factor-beta protein levels in
      culture supernatants over control levels. Gelatin zymography demonstrated a siRNA
      dose-dependent decrease in active MMP-2 enzyme levels. Bradykinin, an effector
      molecule of the kallikrein system, is known to stimulate tissue plasminogen
      activator production. Paradoxically, however, tissue plasminogen activator
      protein levels were augmented with increasing kallikrein mRNA silencing. This was
      accompanied by a dose-dependent decrease in low-density lipoprotein receptor
      related protein mRNA levels, indicating that increased tissue plasminogen
      activator levels were due to an attenuation of receptor-mediated protease
      clearance. CONCLUSION: These data lend strong support to the hypothesis that
      kallikrein exerts antifibrotic, renoprotective effects that are independent of
      its classical haemodynamic actions.

PMID- 18090546
TI  - Dose-dependent titration of prorenin and blood pressure in Cyp1a1ren-2 transgenic
      rats: absence of prorenin-induced glomerulosclerosis.
AB  - OBJECTIVE: Prorenin has been associated with cardiovascular disease and the
      development of glomerulosclerosis via a renin/prorenin receptor. In cyp1a1ren-2
      transgenic rats, prorenin levels and arterial pressure can be increased by oral
      administration of indole-3-carbinol (I3C). The transgenic strain has been used as
      a model of malignant hypertension. METHODS: The present study was designed to
      test the hypotheses that (i) low doses of I3C would result in dose-dependent
      sustained increases in arterial pressure without signs of malignancy, making
      cyp1a1ren-2 transgenic rats a useful model to study nonmalignant hypertension,
      and (ii) cyp1a1ren-2 transgenic rats would develop glomerulosclerosis when they
      were chronically exposed to 0.125% I3C in their diet. RESULTS: I3C treatment for
      2 weeks resulted in increases of plasma prorenin concentrations and arterial
      pressure in a dose-dependent manner. Rats thrived well over a period of 12 weeks
      on dietary I3C concentrations (wt/wt) of 0.125%. Plasma prorenin concentration
      rose from 0.1 +/- 0.1 microg to 17.9 +/- 5.0 mug angiotensin I/ml per h (P <
      0.01) and mean arterial pressure increased to a plateau of 170 +/- 5 mmHg (P <
      0.001) between weeks 6 and 12. After 12 weeks of 0.125% I3C, rats exhibited
      moderate hypertensive renal vasculopathy, but no histological signs of
      glomerulosclerosis. CONCLUSIONS: The cyp1a1ren-2 transgenic rat model allows for
      chronic dose-dependent titration of arterial pressure by a simple and non
      invasive intervention, making this strain a useful model to study malignant and
      nonmalignant arterial hypertension. High circulating prorenin levels per se do
      not cause glomerulosclerosis.

PMID- 18090547
TI  - Basal nitric oxide synthase activity is a major determinant of glomerular
      haemodynamics in humans.
AB  - BACKGROUND: Experimental data suggest that increased nitric oxide synthase (NOS)
      activity contributes to preglomerular vasodilation and subsequent glomerular
      hyperfiltration. Whether such a relationship also exists in the human renal
      vasculature has not yet been adequately determined. METHODS AND RESULTS: We
      assessed systemic, renal, and intragomerular haemodynamics in 310 subjects with
      normal renal function [glomerular filtration rate (GFR) > 60 ml/min per 1.73 m],
      before and after NOS inhibition with L-Nmonomethyl arginine (L-NMMA). Subjects
      were arbitrarily divided into tertiles according to their basal NOS activity, as
      assessed by the decrease in renal plasma flow in response to L-NMMA (high -23.4
      +/- 8.1 versus medium -10.8 +/- 2.2 versus low -1.0 +/- 4.8%). Resting GFR
      differed significantly between tertiles: high 114 +/- 21 versus medium 109 +/- 19
      versus low 104 +/- 21 ml/min per 1.73 m; analysis of variance P = 0.003. In a
      multiple stepwise regression analysis, basal NOS activity was the major factor to
      explain resting GFR (beta = -0.344; P < 0.001). Body weight (beta = -0.295; P <
      0.001) and age (beta = -0.164; P < 0.001) emerged as additional factors, whereas
      body mass index and blood pressure did not enter the final model. The close
      relationship between resting GFR and basal NOS activity was also mirrored in the
      renal microcirculation, as demonstrated by an exaggerated effect of L-NMMA on the
      increase in arteriolar resistance, particularly that of the afferent (RA)
      arteriole, with higher basal nitric oxide (NO) activity (RA: high +1542 +/- 1065
      versus medium +1024 +/- 718 versus low +675 +/- 861 dyne/s per cm; P < 0.001).
      CONCLUSION: Our data clearly support experimental evidence linking NOS activity
      with increased glomerular filtration, and suggest that basal NO activity is also
      a major determinant of glomerular haemodynamics in the human renal vasculature.

PMID- 18090548
TI  - Plasma B-type natriuretic peptide level is associated with left ventricular
      hypertrophy among obstructive sleep apnoea patients.
AB  - OBJECTIVES: To examine whether increased plasma levels of B-type natriuretic
      peptide (BNP) are associated with cardiac structural and functional abnormalities
      in obstructive sleep apnoea (OSA) patients, taking into consideration the
      confounding effect of obesity. MEASUREMENTS: In a cross-sectional study,
      polysomnography, echocardiography and the measurement of the serum levels of BNP
      were performed in 235 consecutive subjects (age 52 +/- 14 years) visiting our
      sleep clinic. Left ventricular hypertrophy (LVH) [left ventricular mass index
      (LVMI) > or = 125 g/m in men, and > or = 110 g/m in women] and cardiac diastolic
      function (E/A ratio) were determined by echocardiography. RESULTS: The LVMI,
      prevalence rate of LVH and body mass index (BMI) were higher, and the E/A ratio
      lower in the subjects with severe OSA (apnoea-hypopnoea index > or = 30/h, n =
      146, LVH 80%) than in those with mild to moderate OSA (n = 89, LVH 35%; P <
      0.01), although plasma BNP levels were similar in the two groups. Although the
      log-transformed plasma BNP level showed a negative correlation with BMI, the
      results of binary logistic regression analysis demonstrated that the quintile
      value of BNP was an independent significant variable for the identification of
      LVH (adjusted odds ratio in quintile 5 = 4.01, 95% confidence interval 1.18
      13.70, P < 0.01), even after adjusting for obesity and other risk factors.
      CONCLUSION: An increased likelihood of cardiac structural and functional
      abnormalities was observed with increasing severity of OSA. Increased plasma
      levels of BNP do seem to reflect an increased likelihood of LVH in patients with
      severe OSA.

PMID- 18090549
TI  - Use of inhaled corticosteroids and the risk of non-fatal acute myocardial
      infarction.
AB  - BACKGROUND: Use of inhaled corticosteroids may reduce the risk of acute
      myocardial infarction (MI) through reductions in systemic inflammation and C
      reactive protein. OBJECTIVES: To examine the association between the use of
      inhaled corticosteroids and the risk of non-fatal acute MI. METHODS: In the Dutch
      PHARMO record linkage system database, we conducted a case-control study (2476 MI
      cases), nested in a cohort of antihypertensive drug users. The use of inhaled
      corticosteroids 100 days before the index date was compared with never use. We
      adjusted the analyses for the severity of the underlying respiratory disease and
      general drug and disease history. RESULTS: We found that the use of inhaled
      corticosteroids was not associated with a decreased risk of non-fatal MI in
      antihypertensive drug users after adjustment for the underlying respiratory
      disease severity, adjusted odds ratio (OR) 1.24, 95% confidence interval (CI)
      0.97-1.57. A higher daily dose (adjusted OR 1.82, 95% CI 0.80-4.13) and longer
      duration of use (adjusted OR 1.28, 95% CI 0.90-1.81) were not associated with a
      decreased risk of non-fatal MI. An inhaled corticosteroid dispensing in the 30
      days before the index date was not protective but resulted in a 1.7-fold
      increased risk of non-fatal MI. CONCLUSION: Our results do not support the
      hypothesis that inhaled corticosteroids protect against the risk of non-fatal MI
      by a reduction of systemic inflammation.

PMID- 18090550
TI  - Arterial stiffness and central hemodynamics in treated hypertensive subjects
      according to brachial blood pressure classification.
AB  - BACKGROUND: International recommendations have classified brachial blood pressure
      (BP) in subgroups enabling better cardiovascular risk stratification. Central BP
      is an independent predictor of cardiovascular risk, differing from brachial BP
      through the predominant influence of arterial stiffness and wave reflections.
      Central BP has never been studied in relation to international guidelines for
      brachial BP classification. METHODS: In 580 chronically treated hypertensive
      subjects we measured: carotid-femoral pulse wave velocity (PWV), carotid artery
      augmentation index (AI) and carotid blood pressures, using applanation tonometry
      and pulse wave analysis, and using brachial BP for carotid pressure wave
      calibration. RESULTS: For each given brachial value, carotid systolic blood
      pressure (SBP) and PP were significantly lower than the corresponding brachial
      SBP and PP. This pressure amplification was significantly lower in the 'optimal'
      and 'normal' BP ranges (6.8-7.4 mmHg) than in the higher BP ranges (10.1-11.3
      mmHg), mainly depending on heart rate (HR) and PWV levels. PWV gradually
      increased as a function of brachial BP classification and was a significant
      predictor of this classification independently of age, drug treatment,
      atherosclerotic lesions and even mean BP. Finally, PWV was a highly sensitive
      marker of the effective BP control throughout all decades of age. CONCLUSION:
      Under chronic antihypertensive therapy, central BP does not strictly parallel the
      corresponding brachial BP classification, depending on differences in aortic
      stiffness and HR. Whether aortic PWV might predict the brachial BP classification
      and/or the presence of effective BP control, as suggested in this study, needs
      further confirmation.

PMID- 18090551
TI  - From 'optimal' to 'borderline' blood pressure in subjects under chronic
      antihypertensive therapy.
AB  - OBJECTIVES: The ESH2003 report (J Hypertens 2003, 21:1011-1053) has classified
      brachial blood pressure into six groups reflecting the consistently increasing
      cardiovascular risk caused by high blood pressure. Chronically treated
      hypertensive individuals with well-controlled blood pressure retain higher
      cardiovascular risk than normotensive untreated individuals. Differences between
      these groups in arterial stiffness, pressure wave reflections and central blood
      pressure, which are all predictors of cardiovascular risk independently of
      peripheral blood pressure, have never been studied. METHODS: A cohort of 216
      treated subjects with controlled hypertension was compared with 105 never-treated
      normotensive controls, according to the ESH2003 blood pressure groups. Aortic
      stiffness (pulse wave velocity; PWV), carotid wave reflections (augmentation
      index; AI) and carotid pressures were measured non-invasively, by pulse wave
      analysis. Systolic blood pressure (SBP) and pulse pressure (PP) amplification
      between brachial and carotid arteries were estimated. RESULTS: The distribution
      of subjects in each subgroup of the untreated and treated populations was:
      'optimal', 21 versus 43; 'normal', 44 versus 77; 'borderline', 40 versus 96.
      Brachial blood pressure, carotid SBP and PP did not differ between the two
      populations, but a constant interaction between blood pressure classification and
      treatment effect on PWV, AI and blood pressure amplification was found. Compared
      with untreated subjects, treated subjects had higher AI and lower blood pressure
      amplification (in the optimal group) and higher PWV (in the borderline group).
      CONCLUSION: 'Optimal' to 'borderline' blood pressure control in chronically
      treated hypertensive individuals is associated with impaired properties of the
      large and small arteries. These results suggest that antihypertensive treatment
      strategies with more beneficial effects on arterial properties are needed.

PMID- 18090553
TI  - Need to clarify when measurements should be made during the day for home blood
      pressure monitoring.

PMID- 18090552
TI  - A cross-national study of the persistence of antihypertensive medication use in
      the elderly.
AB  - INTRODUCTION: Little is known about cross-national comparisons of the persistence
      of antihypertensive medication treatment, trends in persistence, and factors
      associated with persistence. The aim of this study was to describe and compare
      patterns of use of antihypertensive drugs in a population of elderly patients in
      the United States (Pennsylvania), Canada (British Columbia) and the Netherlands.
      METHODS: A retrospective cohort study of Medicare enrollees in a state pharmacy
      assistance programme in Pennsylvania (USA), residents from British Columbia
      (Canada) and residents from the Netherlands registered in the PHARMO database was
      conducted. Each population included patients 65 years and older who were
      initiated on blood pressure-lowering treatment between 1 January 1998 and 31
      December 2003 and who had continuous follow-up for at least 365 days. In these
      populations, the proportion of patients with at least 180 consecutive days
      without medication available (non-persistence) were identified as were predictors
      of non-persistence using Cox proportional hazards. RESULTS: A total of 9664
      Medicare enrollees (USA), 25 377 residents from British Columbia and 24 603
      residents from the Netherlands were evaluated. During the first year after the
      initiation of treatment, the percentage of patients with at least 180 days
      without medication was 23.3% in Pennsylvania, 23.4% in British Columbia and 24.0%
      in the Netherlands. After 6 years, these percentages increased to 41.1, 36.3 and
      38.2%, respectively. Factors associated with non-persistence were different
      between the three countries. CONCLUSION: Despite differences in factors
      associated with persistence, non-persistence patterns are strikingly similar in
      all three populations. This suggests that the problem of non-persistence
      transcends international boundaries.

PMID- 18090555
TI  - Prediction of cardiovascular outcome by the estimated glomerular filtration rate
      and estimated creatinine clearance in the high-risk hypertension population of
      the VALUE trial.

PMID- 18090556
TI  - Retinol and retinol-binding protein in cerebrospinal fluid: can vitamin A take
      the "idiopathic" out of idiopathic intracranial hypertension?

PMID- 18090557
TI  - Retinol-binding protein and retinol analysis in cerebrospinal fluid and serum of
      patients with and without idiopathic intracranial hypertension.
AB  - BACKGROUND: Several studies have implicated vitamin A-related compounds in the
      pathogenesis of idiopathic intracranial hypertension (IIH). The goal of this
      study was to compare cerebrospinal fluid (CSF) and serum concentrations of
      retinol and retinol-binding protein (RBP) in subjects with and without IIH.
      METHODS: CSF and serum samples were collected from 87 subjects. The study
      population was composed of subjects with IIH (IIH group, n = 28), subjects with
      non-IIH neurologic conditions (neurology controls, n = 42), and subjects
      undergoing preoperative lumbar puncture but with no known neurologic conditions
      (anesthesia controls, n = 17). RBP levels (nM) were determined using radial
      immunodiffusion, and retinol levels (nM) were determined using high-performance
      liquid chromatography. RESULTS: The retinol/RBP ratio was greater in CSF than in
      serum, especially in subjects with IIH. CONCLUSIONS: The finding of increased
      levels of unbound retinol in the CSF of subjects with IIH provides further
      evidence that vitamin A may be involved in the pathogenesis of IIH. Comparative
      statistical analyses revealed multivariate relationships that demonstrate the
      need to further investigate correlations between vitamin A and RBP levels in CSF
      and serum.

PMID- 18090558
TI  - The prevalence of relative afferent pupillary defects in normal subjects.
AB  - BACKGROUND: Observational and pupillographic studies of small numbers of normal
      subjects have shown that a small (<0.3 log units) relative afferent pupil defect
      (RAPD) is present in a minority. We have extended the investigation of the
      prevalence of RAPD to a larger number of normal subjects. METHODS: A total of 102
      subjects were examined by observation and pupillography. The swinging flashlight
      test was performed using neutral density filters for quantification. During the
      pupillographic procedure, light-emitting diodes were placed in front of each eye,
      alternately flashing for 2.5 seconds with a 0.5 second break. A binocular real
      time pupillometer recorded the direct and consensual pupillary responses. After
      artefact detection and removal, the amplitudes of pupillary response were
      determined and plotted against stimulus intensity. The means of the direct and
      the consensual responses were used for automated calculation of RAPD. RESULTS: By
      observation, there was no RAPD in 87 (85%) subjects; there was an RAPD of 0.15
      log units in 13 (13%), and an RAPD of 0.3 log units in 2 (2%). By pupillography,
      there was an RAPD of 0.07 log units in 53 (52%) subjects, an RAPD between 0.08
      and 0.22 log units in 43 (42%) subjects, and an RAPD between 0.23 and 0.39 log
      units in 6 (6%) subjects. CONCLUSIONS: Observation and pupillographic
      measurements of the swinging light test in a large normal subject cohort has
      confirmed that an RAPD is present in a small minority but that it does not exceed
      0.39 log units. The RAPD in these subjects may be explained by inaccuracy of
      measurement or by asymmetries in the connections between visual pathways and
      pretectal nuclei in the midbrain.

PMID- 18090559
TI  - Spatial processing in Balint syndrome and prosopagnosia: a study of three
      patients.
AB  - BACKGROUND: Spatial analysis may be subdivided into between-object and within
      object spatial coding. We investigated the contribution of various visual cues to
      grouping processes that might determine whether single or multiple objects were
      perceived and therefore which type of spatial coding would be used for a
      stimulus. METHODS: We asked three patients to make shape judgments with a series
      of displays showing triangular arrangements, moving from more implicit triangles
      defined by separate objects at the apices (between-object spatial coding) to more
      explicit triangles with line edges or surface texture (within-object spatial
      coding). RESULTS: In two patients with prosopagnosia, within-object spatial
      judgments were impaired, whereas between-object spatial judgments were normal. In
      a patient with Balint syndrome, the reverse pattern was obtained. Surface texture
      but not outline closure led to mandatory within-object coding in the
      prosopagnosic patients, whereas outline or surface texture was sufficient to
      support intact within-object spatial judgments in the patient with Balint
      syndrome. Illusory contours were ineffective in promoting within-object coding in
      either condition. CONCLUSIONS: These findings support the existence of parallel
      representations of space for within-object and between-object processing and
      reveal the efficacy of different cues in determining which representation is
      potentially accessible.

PMID- 18090560
TI  - Closely spaced stressful life events precede the onset of benign essential
      blepharospasm and hemifacial spasm.
AB  - BACKGROUND: The purpose of this study was to assess the possible role of major
      stressful life events, complicated grief, and depression in the pathogenesis of
      benign essential blepharospasm (BEB) and hemifacial spasm (HFS). METHODS: This
      was a case-control study involving 23 participants with BEB/HFS and 23 control
      subjects, comparing the frequency of major stressful life events, depression on
      the Beck Depression Inventory-II, and complicated grief on the Inventory of
      Complicated Grief. RESULTS: There was no difference in the rate of depression or
      complicated grief between participants with BEB/HFS (57%) and control subjects
      (48%). Participants with BEB/HFS experienced a significantly (P = 0.0048) shorter
      time interval between two major stressful life events (median, 0.3 year) than did
      the control group (median, 3.0 years). The proportion of participants who had
      suffered two major stressful lifetime events separated by 1 year or less was
      significantly greater for participants with BEB/HFS than for control subjects (P
      = 0.0007). CONCLUSIONS: The onset of BEB and HFS was often preceded by a major
      lifetime stressor. The development of these conditions was significantly related
      to the number of stressful life events occurring within the preceding year rather
      than to the total number of stressful life events. Subjects who sustain closely
      spaced stressful life events may be at increased risk of developing BEB and HFS.

PMID- 18090561
TI  - Endovascular treatment of a bilateral ophthalmic-ethmoidal artery dural
      arteriovenous fistula.
AB  - A 76-year-old man developed blurred vision, and cerebral angiography disclosed an
      anterior skull base dural arteriovenous fistula (DAVF) supplied by both ethmoidal
      branches of the ophthalmic arteries and draining through a single cortical vein.
      Selective catheterization of both ophthalmic arteries distal to the origin of the
      central retinal arteries and occlusion the fistula feeders with injections of n
      butyl cyanoacrylate glue led to complete occlusion of the fistula with
      preservation of retinal perfusion. The visual symptoms are attributed to impaired
      retinal perfusion as the result of a steal phenomenon. With care, a DAVF in this
      location can be successfully treated endovascularly while preserving retinal
      perfusion by embolizing the ophthalmic artery distal to the origin of the central
      retinal arteries and avoiding any backflow of embolizing material.

PMID- 18090562
TI  - Posterior ischemic optic neuropathy after minimally invasive prostatectomy.
AB  - Two patients developed postoperative ischemic optic neuropathy (ION) after
      laparoscopic radical prostatectomy. One operation was robotically assisted; the
      other was performed with the conventional laparoscopic technique. These new
      minimally invasive techniques offer many advantages, but they require steep
      supine head-flexed (Trendelenburg) positioning. Until they are mastered by
      surgeons, operative times may be prolonged beyond those associated with the
      traditional technique. As a result, ION may occur more frequently.

PMID- 18090563
TI  - Bilateral macular retinitis as the presenting feature of subacute sclerosing
      panencephalitis.
AB  - Two patients presented with retinitis as the initial clinical manifestation of
      subacute sclerosing panencephalitis (SSPE), a delayed neurologic complication of
      measles. In one patient, the ocular involvement preceded the neurologic symptoms
      by 4 weeks and in the other patient by 4 years. The diagnosis of SSPE was
      suspected when neuropsychiatric manifestations appeared and was confirmed by the
      typical panencephalitic electroencephalography changes, neuroimaging features of
      panencephalitis, and high titers of measles antibodies in serum and cerebrospinal
      fluid. Although SSPE is an untreatable illness, recognition of this unusual
      presentation is valuable to allow earlier diagnosis and institution of palliative
      measures.

PMID- 18090564
TI  - Isolated cortical visual loss with subtle brain MRI abnormalities in a case of
      hypoxic-ischemic encephalopathy.
AB  - A 16-year-old boy who was briefly asystolic and hypotensive after a motor vehicle
      accident complained of abnormal vision after recovering consciousness. Visual
      acuity was normal, but visual fields were severely constricted without clear
      hemianopic features. The ophthalmic examination was otherwise normal. Brain MRI
      performed 11 days after the accident showed no pertinent abnormalities. At 6
      months after the event, brain MRI demonstrated brain volume loss in the primary
      visual cortex and no other abnormalities. One year later, visual fields remained
      severely constricted; neurologic examination, including formal neuropsychometric
      testing, was normal. This case emphasizes the fact that hypoxic-ischemic
      encephalopathy (HIE) may cause enduring damage limited to primary visual cortex
      and that the MRI abnormalities may be subtle. These phenomena should be
      recognized in the management of patients with HIE.

PMID- 18090565
TI  - Room tilt illusion influenced by head position.
AB  - After a low brainstem stroke, a 73-year-old man experienced episodes of 90
      degrees tilting of the visual environment in the sagittal plane evoked or
      terminated by voluntarily changing his head position. The episodes ceased 10 days
      after the stroke. This provocation by head position supports the idea that
      pathologic visual-vestibular interaction is at the basis of the room tilt
      illusion.

PMID- 18090566
TI  - Migraine-like visual hallucinations as the presenting manifestations of focal
      seizures in neurocysticercosis.
AB  - We report three patients with visual hallucinations as the initial manifestations
      of neurocysticercosis (NCC) in whom migraine was the first diagnosis. The correct
      diagnosis was suspected when electroencephalograms were abnormal and was
      confirmed by characteristic brain imaging. The visual hallucinations ceased
      promptly after treatment with antiepileptic and anti-NCC medications. We caution
      that NCC may present with focal seizures manifesting as visual hallucinations
      with features of migraine.

PMID- 18090567
TI  - Exotropia and face turn in children with homonymous hemianopia.
AB  - Four children developed homonymous hemianopia, exotropia with the deviating eye
      pointing in the direction of the field defect, and a face turn toward the side of
      the defect following complete third cranial nerve palsy after brain tumor
      resection, an in utero middle cerebral artery infarction, nonaccidental head
      trauma, and a hemispherectomy for an intractable seizure disorder. We present
      evidence that the exotropia and face turn are part of an adaptive mechanism to
      increase the useful visual field.

PMID- 18090568
TI  - Reversible tonic pupils.
AB  - A 36-year-old man with a remote history of Hodgkin lymphoma and a recent history
      of non-Hodgkin lymphoma (NHL) developed tonic pupils and absent deep tendon
      reflexes in the lower extremities. One year later, pupils were normal except for
      slight iris segmental contraction to light. Over the next 2 years, the patient
      remained asymptomatic, and pupils remained unchanged. The NHL went into
      remission, and no other neurologic manifestations appeared. This is the first
      report of reversible tonic pupils. They may have a pathogenesis different from
      that typically seen in irreversible tonic pupils.

PMID- 18090569
TI  - Tonic pupil as the presenting sign of relapsed acute myeloid leukemia.

PMID- 18090570
TI  - Generalized myasthenia gravis triggered by cataract surgery.

PMID- 18090571
TI  - Benztropine-induced Esotropia and Mydriasis.

PMID- 18090572
TI  - Idiopathic intracranial hypertension in a transgender man.

PMID- 18090573
TI  - Simultaneous ischemic optic neuropathy and third cranial nerve palsy in giant
      cell arteritis.

PMID- 18090574
TI  - Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
      Fort Lauderdale, Florida May 6-10, 2007.

PMID- 18090575
TI  - The 59th Annual Meeting of the American Academy of Neurology, Boston,
      Massachusetts April 28-May 5, 2007.

PMID- 18090576
TI  - Platinum resistance related to a functional NER pathway.

PMID- 18090577
TI  - The International Association for the Study of Lung Cancer lung cancer staging
      project: proposals regarding the clinical staging of small cell lung cancer in
      the forthcoming (seventh) edition of the tumor, node, metastasis classification
      for lung cancer.
AB  - BACKGROUND: Small cell lung cancer (SCLC) is usually classified using the limited
      and extensive definition. The tumor, node, metastasis (TNM) classification should
      also be applicable to SCLC, but it has only been reported in small surgical
      series. The current analysis looks to the impact of the TNM system on the
      clinical staging of SCLC and of the new International Association for the study
      of Lung Cancer (IASLC) proposals. METHODS: Using the IASLC database, survival
      analyses were performed for clinically staged patients. Prognostic groups were
      compared, and the new IASLC TNM proposals were applied to this population and to
      the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: The
      IASLC database contained 12,620 eligible cases of small cell histology. TNM
      staging was available for 8088 patients. Survival was directly correlated to both
      T and N category. Differences were more pronounced in patients without
      mediastinal or supraclavicular nodal involvement. Stage grouping using the sixth
      edition of TNM also differentiates survival except between IA and IB. Patients
      with pleural effusion regardless of the cytology have an intermediate prognosis
      between limited and extensive disease. The IASLC proposals for the seventh
      edition of the TNM classification also apply to this series of SCLC and to the
      SEER database. CONCLUSION: TNM staging is recommended for SCLC, and
      stratification by stage I-III should be incorporated in clinical trials of early
      stage disease. Further studies are needed to clarify the impact of pleural
      effusion and the extent of N3 disease.

PMID- 18090578
TI  - Validation of the proposed International Association for the Study of Lung Cancer
      non-small cell lung cancer staging system revisions for advanced
      bronchioloalveolar carcinoma using data from the California Cancer Registry.
AB  - BACKGROUND: Recently, the International Association for the Study of Lung Cancer
      (IASLC) has proposed significant modifications to the existing TNM and stage
      grouping classifications affecting the T4 and M descriptors. We set out to
      validate this staging system for bronchioloalveolar carcinoma (BAC) cases using
      data from the California Cancer Registry (CCR). METHODS: We identified 1909
      patients from the CCR between 1999 and 2003 with histologically confirmed BAC and
      complete TNM staging and reclassified them according to the IASLC proposed
      staging revisions. There were 657 patients with stage IIIB and IV disease who
      formed the primary analysis of the changes to T4 and M descriptors. Surveillance
      Epidemiology and End Results (SEER) extent of disease codes (EOD) were used to
      identify various T4 and M descriptors. The primary outcome measured was overall
      survival (OS) for stage-specific comparisons of the existing to the proposed
      staging systems, using the Kaplan-Meier method. Multivariate survival analyses
      were performed using Cox proportional hazards ratios. RESULTS: Using the proposed
      criteria, 162 (25%) of the 657 patients with advanced BAC were reclassified: 73
      patients with multiple lesions in the same lobe as T3 (stage II T3N0M0 [n = 53],
      stage IIIA T3N1-2M0 [n = 18], stage IIIB T3N3M0 [n = 1] or T3NXM0 [n = 1]); 89
      patients with ipsilateral intrapulmonary metastasis were reclassified as T4
      (stage IIIA T4N0-N1M0 [n = 54], stage IIIB T4N2-3M0 [n = 23] or T4NXM0 [n = 12]).
      Univariate and multivariate survival analysis of this validation set revealed an
      improved fit for the proposed IASLC staging system compared with the existing
      staging system. CONCLUSIONS: The proposed IASLC staging system modifications
      accurately reflect survival characteristics for BAC and represent an improvement
      compared with the existing staging system.

PMID- 18090579
TI  - Mutational analysis in cytological specimens of advanced lung adenocarcinoma: a
      sensitive method for molecular diagnosis.
AB  - INTRODUCTION: The discovery that somatic mutations in the epidermal growth factor
      receptor (EGFR) gene are associated with sensitivity to the EGFR tyrosine kinase
      inhibitors (TKIs) in lung adenocarcinomas, whereas Kras mutations are associated
      with resistance, has generated excitement among both clinicians and researchers
      studying non-small cell lung cancer (NSCLC). Mutational analysis may soon be very
      useful in choosing among a wide range of targeted therapies to individualize
      treatment to tumor characteristics. This analysis would be even more useful in
      patients with advanced NSCLC, in whom cytological specimens are often the only
      material available. METHODS: We analyzed 23 archived cytologic specimens of
      advanced/metastatic lung adenocarcinomas for mutations in EGFR exons 18 to 21,
      and Kras exon 2. RESULTS: Our data show that our cytological specimens were
      perfectly adequate for the molecular analysis of EGFR and Kras mutations. EGFR TK
      domain mutations were found in three cases (13.04%) and were associated with both
      female gender (p = 0.02) and a nonsmoking history (p = 0.008). Moreover, we
      explored the relationship between EGFR mutation status and the presence of Kras
      mutations. Kras mutations involving codon 12 in exon 2 were found in 5 (21.73%)
      of the 23 adenocarcinomas and were associated, where known, with smoking habits.
      We never found EGFR alterations in tumors with Kras mutations. CONCLUSIONS: Our
      results provide oncologists with a highly accurate laboratory method to identify
      biological predictors of the efficacy of different therapies, and they may have
      an important impact on clinical practice. This method may be particularly useful
      in patients with advanced/metastatic NSCLC.

PMID- 18090580
TI  - A systematic review of quality of life associated with standard chemotherapy
      regimens for advanced non-small cell lung cancer.
AB  - PURPOSE: Systemic chemotherapy is accepted as a standard of care for patients
      with advanced non-small cell lung cancer (NSCLC). Although survival outcomes are
      equivalent among standard chemotherapy regimens, it is unknown whether the
      quality of life (QOL) outcomes are also comparable. We evaluated available
      literatures to summarize the state of current knowledge and provide suggestions
      for future studies. METHODS: Using PUBMED/MEDLINE database, a systematic review
      of randomized controlled phase III trials of advanced NSCLC reporting QOL as one
      of the end points was conducted. Trials were included if standard chemotherapy
      regimens (as defined by The American Society of Clinical Oncology 2003
      recommendations) were used in at least two arms of a trial. Two reviewers
      independently extracted data and evaluated the characteristics of QOL reporting,
      analyses, and results. RESULTS: The search criteria identified 14 trials (6665
      patients). Of these, 13 trials used validated QOL instruments and were included
      for review. The QOL reporting/analysis techniques were heterogeneous. We included
      nine trials, which reported the rate of completed baseline assessment and
      compliance survivors at analysis greater than 50%, for data synthesis. Of these,
      only one trial found a significant difference in QOL between the comparator arms:
      paclitaxel plus cisplatin was better than teniposide plus cisplatin. CONCLUSION:
      Based on our review, it seems unlikely that a major difference exists in the
      global QOL associated with standard chemotherapy regimens for advanced NSCLC.
      Although QOL reporting format is largely acceptable, a lack of uniformity in
      analysis and a poor compliance to QOL assessment made between-trial comparisons
      difficult.

PMID- 18090581
TI  - Prognostic factors in patients with pathologic T1-2N1M0 disease in non-small cell
      carcinoma of the lung.
AB  - INTRODUCTION: Patients with stage II non-small cell lung carcinoma (NSCLC)
      represent a heterogeneous subgroup with variable 5-year survival rates. The
      influence of the type of lymph node involvement on survival and recurrence was
      investigated. METHODS: A total of 128 consecutive patients who underwent complete
      tumor resection and mediastinal lymph nodes dissection for pT1-2N1M0 NSCLC
      between July 1991 and December 2003 were retrospectively reviewed. RESULTS: The
      overall 5-year survival of patients with T1-2N1M0 disease was 42.2%. Although pT
      status, histology, surgical procedure, and adjuvant therapy did not affect
      survival for pT1-2N1M0 patients, the 5-year survival rate differed significantly
      according to the type of lymph node involvement. The 5-year survival rate for
      patients with main bronchial lymph node involvement, interlobar and lobar lymph
      node involvement, and segmental bronchial lymph node involvement was 19.7%,
      39.8%, and 59.7%, respectively. The survival curves of these three groups had
      significant differences. Fifty-five patients had cancer recurrence, and the type
      of lymph node involvement did not affect the pattern of cancer relapse.
      CONCLUSIONS: In patients with stage II NSCLC, survival differs according to the
      type of lymph node involvement: patients with only segmental lymph node
      involvement have a better prognosis and the disease seems to be at an early
      stage, whereas patients with main bronchial lymph node involvement have a poorer
      prognosis, and main bronchial lymph node involvement represents more advanced
      disease. Patients with pN1 disease represent a heterogeneous group that may be
      subdivided according to the level of the involved N1 station, not pT factor.

PMID- 18090582
TI  - Frequency and prognostic significance of preoperatively detected enlarged
      regional lymph nodes in patients with pathological stage I non-small cell lung
      cancer following resection.
AB  - PURPOSE: To explore the clinical significance of enlarged regional lymph nodes in
      patients with pathological stage I non-small cell lung cancer (NSCLC). MATERIAL
      AND METHODS: We retrospectively reviewed the tumor registry of the International
      Association for the Study of Lung Cancer (IASLC) Staging Database to identify
      6995 patients between January 1, 1990 and December 31, 2000 with clinical stage
      I, II, and IIIA tumors (cT1-2N0-2M0, excluding T3N0-2M0 cases) who proved to have
      pathological stage I NSCLC (T1-2N0M0, pStage I). The frequency of enlarged nodes
      in patients with pStage I disease is reported, and the overall survival of these
      patients who had enlarged regional lymph nodes was compared with that of patients
      with pStage I disease with normal size regional lymph nodes. RESULTS: Enlarged
      regional lymph nodes (cN1-2) were seen in approximately 12% of patients with
      pStage I disease. Median survival for patients with enlarged versus normal nodes
      was 102 versus 107 months (hazard ratio 1.16, p = 0. 01). Survival curves
      converged at 8 years postsurgery. CONCLUSIONS: Enlarged regional lymph nodes are
      uncommon in patients with pStage I NSCLC, and the size of regional lymph nodes in
      these early stage patients does not seem to provide clinically useful prognostic
      information.

PMID- 18090583
TI  - Clinicopathological factors associated with unexpected N3 in patients with
      mediastinal lymph node involvement.
AB  - INTRODUCTION: We have already shown that postoperative survival was poor in p-N3
      patients from the experience of extended radical nodal dissection (ERD: cervical
      and bilateral mediastinal nodal dissection) for lung cancer. In this
      retrospective study, we aimed to clarify the clinicopathological factors
      associated with p-N3 in patients with mediastinal lymph node involvement
      (excluding c-N3) who underwent ERD, and we studied their impact on prognosis.
      METHODS: Between 1996 and April 2006, in patients with lung cancer in the right
      upper lobe, we performed ERD after obtaining informed consent from the patients.
      The study comprised 8 females and 29 males (median age of 60 years), with 15/7/15
      cases of c-N0/c-N1/c-N2, respectively. The clinicopathological records of each
      patient were examined for prognostic factors associated with p-N3, including age,
      gender, histology, c-N number, preoperative serum CEA level, number of metastatic
      stations, and distribution of metastatic nodes according to the system of Naruke
      et al. Because c-N3 cases were excluded from the study, we defined p-N3 as
      unexpected N3. RESULTS: Of the 37 study subjects, 19 (51.4%) had one or more
      metastases to the mediastinal lymph nodes. Of these 19 patients, 10 (52.6%) had
      metastases to cervical and/or contralateral mediastinal lymph nodes (unexpected
      N3; 5-year survival was 0%). C-N factor (c-N2), nonskip N2, multistation
      mediastinal lymph node metastasis, highest mediastinal nodal involvement, and pT
      status were significantly associated with unexpected N3. In particular,
      multistation mediastinal lymph node metastasis and highest mediastinal nodal
      involvement were significant prognostic factors in multivariate analyses.
      CONCLUSIONS: Because unexpected N3 patients showed a poor prognosis after ERD,
      treatment modalities other than surgery should be considered. On the other hand,
      because true N2 patients showed a good outcome after surgery, surgical resection
      may be considered an important therapeutic modality even for N2 patients, given
      that they show single-station mediastinal nodal involvement or c-N0-1.

PMID- 18090584
TI  - Phase I study of two different schedules of bortezomib and pemetrexed in advanced
      solid tumors with emphasis on non-small cell lung cancer.
AB  - INTRODUCTION: Bortezomib and pemetrexed are approved anticancer agents with non
      overlapping mechanisms of action and toxicity. We examined the safety and
      tolerability of pemetrexed in combination with two different schedules of
      bortezomib in patients with advanced solid tumors. METHODS: Two separate dose
      escalating arms (arm A and arm B) were conducted simultaneously. Patients
      received pemetrexed on day 1 (D1) (500-600 mg/m2 IV) every 21 days. In arm A,
      bortezomib was given twice weekly (0.7-1.3 mg/m2 on D1, 4, 8, and 11). In arm B,
      bortezomib was given weekly (1.0-1.6 mg/m2 on D1 and 8). RESULTS: We treated 27
      patients on four dose levels in arm A and three dose levels in arm B. Tumor types
      included lung (n = 16), adenoid cystic carcinoma (n = 2), prostate (n = 2),
      sarcoma (n = 2), breast (n = 1), thymus (n = 1), head and neck (n = 1), and
      gastrointestinal(n = 2). Dose-limiting toxicities were seen in arm A only; grade
      3 asthenia (n = 2), grade 3 transaminitis and dehydration (n = 1). The most
      common grade 3/4 toxicity was neutropenia. Of 26 evaluable patients, 2 patients
      had partial response (1 in arm A and 1 in arm B), 13 had stable disease (7 in arm
      A and 6 in arm B), and 11 had progression (6 in arm A and 5 in arm B). Of the 16
      patients with non-small cell lung cancer, 2 (12.5%) had partial response and 9
      had stable disease, for a disease control rate of 68.8%. Recommended phase II
      dose for arm A is pemetrexed 500 mg/m2 and bortezomib 1.3 mg/m2 twice weekly. For
      arm B, the recommended dose is pemetrexed 500 mg/m2, bortezomib 1.6 mg/m2 weekly.
      CONCLUSIONS: Pemetrexed with bortezomib is feasible and tolerable at recommended
      single-agent doses. Based on the observed efficacy, a phase II study in non-small
      cell lung cancer is warranted.

PMID- 18090585
TI  - Prognostic factors after combined modality treatment of squamous cell carcinoma
      of the esophagus.
AB  - INTRODUCTION: In a previous study of prognostic factors in patients with loco
      regionally advanced adenocarcinoma of the esophagus treated with chemo
      radiotherapy (CRT) followed by resection, we found that residual nodal disease
      was most prognostic of outcome. In this study, we evaluated prognostic factors
      among patients with squamous cell carcinoma (SCC) of the esophagus who have
      undergone a similar treatment regimen. METHODS: A retrospective review of
      patients with SCC of the esophagus who received CRT before esophagectomy. Data
      collected included demographics, CRT details, pathologic findings, and survival.
      Statistical methods included recursive partitioning and Kaplan-Meier analyses.
      RESULTS: From 1996 to 2006, 91 patients were appropriate for this analysis.
      Complete pathologic response in the primary tumor (pt-pCR) occurred in 49
      patients (53.8%), including 10 of 91 (10.9%) who had a pt-pCR but residual nodal
      disease. Recursive partitioning analysis identified three prognostic groups: (1)
      group 1 (n = 52), patients with minimal residual local disease (pt-pCR and T1-N
      any); (2) group 2 (n = 28), patients with residual T2 disease (N0 and N1) and
      patients with T3-4N0 disease; and (3) group 3 (n = 11), patients with residual T3
      4N1 disease. Three-year survival was 68.4% in group 1, 45.6% in group 2, and 0 %
      in group 3 (p < 0.001). CONCLUSIONS: Unlike adenocarcinoma, in which residual
      nodal disease after CRT is the most significant predictor of survival, in SCC of
      the esophagus, pt-pCR or minimal residual local disease after CRT predicts the
      best survival. These findings aid the design of future clinical trials.

PMID- 18090586
TI  - Solitary fibrous tumor of the pleura: evaluation of the origin with 3D CT
      angiography.

PMID- 18090587
TI  - Giant ulcerated pleomorphic liposarcoma of the chest wall.
AB  - Liposarcomas most often originate in the extremities and on the retroperitoneum.
      Primary malignant soft-tissue sarcoma of the chest is a rare entity. Most of them
      are low grade, and complete surgical excision is the preferred therapeutic
      choice. Like most cancers, the incidence of liposarcoma increases with advancing
      age, and subtotal resection is considered a palliative surgical procedure. The
      benefit of adjuvant radiotherapy or chemoradiotherapy for these tumors remains
      controversial.

PMID- 18090588
TI  - Iris metastasis in small-cell lung carcinoma.
AB  - Small-cell lung cancer (SCLC) is characterized by rapid growth and early
      metastasis. Despite its sensitivity to cytotoxic treatment, until now treatments
      have failed to control or cure this disease in most patients. Here, we describe a
      patient with SCLC in which symptoms caused by iris metastasis were the only sign
      of relapse after multimodality treatment.

PMID- 18090589
TI  - Thymoma-associated graft-versus-host disease-like erythroderma.
AB  - We report a 40-year-old woman with recurrent thymoma associated with myasthenia
      gravis, in whom an unusual form of erythroderma developed. A histological
      examination revealed a graft-versus-host disease (GVHD)-like reaction. After high
      dose steroid therapy, the metastatic thymoma lesion in the abdominal cavity was
      reduced in size from 9.5 x 6 x 7.5 cm to 4 x 3 x 1 cm in diameter. Nevertheless,
      the GVHD-like erythroderma become aggravated, her condition worsened, and the
      patient finally suffered from respiratory failure and died of sepsis. A GVHD-like
      reaction may be a rare presentation of thymoma-associated immunological disorders
      such as myasthenia gravis or pure red cell aplasia. Herein, we discuss the
      present case and review pertinent reports of thymoma cases associated with GVHD.

PMID- 18090590
TI  - Palliative radiation for lung cancer metastases to the breast: two case reports.
AB  - Metastases from non-small cell lung cancer to the breast represent an unusual
      diagnosis. We present two cases of metastatic lung cancer to the breast that were
      treated with palliative radiation with achievement of good local control and
      symptom relief. We suggest the use of palliative radiation therapy as an
      effective and simple treatment modality for metastatic disease to the breast.

PMID- 18090591
TI  - Erlotinib-associated alopecia in a lung cancer patient.

PMID- 18090592
TI  - Adjuvant use of epidermal growth factor receptor kinase inhibitors may prevent
      bone metastases in patients with non-small cell lung carcinoma.

PMID- 18090593
TI  - Reply: Randomized controlled trial of resection versus radiotherapy after
      induction chemotherapy in stage IIIA-N2 non-small cell lung cancer.

PMID- 18090606
TI  - Managing a water-seal chest drainage unit.

PMID- 18090607
TI  - The role of albumin in fluid balance.

PMID- 18090608
TI  - Creating a guide for float nurses.

PMID- 18090609
TI  - Assessing complex pain behaviors.

PMID- 18090610
TI  - Using antiseptics to manage infected wounds.

PMID- 18090611
TI  - What is pseudomyxoma peritonei?

PMID- 18090612
TI  - Assess for fall risk, intervene--and bump up patient safety.

PMID- 18090613
TI  - Get the skinny on trans-fatty acids.

PMID- 18090631
TI  - Helping your patient combat lung cancer.

PMID- 18090633
TI  - Job satisfaction survey report.

PMID- 18090634
TI  - Speaking up for medical language interpreters.

PMID- 18090635
TI  - Listen up, MRSA: the bug stops here.

PMID- 18090640
TI  - Emergency challenge.

PMID- 18090646
TI  - When your patient needs long-term-care services...

PMID- 18090648
TI  - Accidental anthracycline extravasation.

PMID- 18090650
TI  - Nutritional considerations in institutionalized elders.
AB  - PURPOSE OF REVIEW: The aim of this article is to emphasize the importance of
      malnutrition in frail institutionalized elderly and discuss recent interventions
      that have been shown to decrease its prevalence. RECENT FINDINGS: A Medline
      search was conducted from 1968 to 2007 under the search terms aging, nutrition,
      and nursing homes. The most current reviews relevant to the care of
      institutionalized elders were selected for inclusion in this report. Recent
      reports have shown that application of screening protocols in long-tem care
      institutions improved nutritional status. A complete physical assessment, with
      special attention to the oral cavity, should be conducted. Monitoring of weight
      and intake should be part of the institutional routine, recognizing that there
      may be differences between prescribed diet and actual intake. Nutritional
      interventions should be tried as early as possible, including enhancement of
      environment and increasing staff to assist with feeding, as malnutrition in this
      population is associated with falls (particularly with deficient vitamin D) and
      increased morbidity and mortality. To optimally facilitate nutritional care of
      nursing home patients reforms are needed to facilitate optimal staffing in the
      institutional setting. SUMMARY: It is important to educate healthcare workers in
      the nursing home about simple interventions that could improve nutritional
      status.

PMID- 18090651
TI  - Vitamin D and cardiovascular disease risk.
AB  - PURPOSE OF REVIEW: Despite our understanding of how to prevent and treat
      traditional cardiovascular risk factors, cardiovascular disease remains the
      leading cause of death of both men and women in the US. Thus, there is widespread
      interest in a number of emerging nontraditional risk factors for the detection of
      early cardiovascular disease in order to implement aggressive preventive
      therapies. 25-Hydroxyvitamin D deficiency has been identified as a potential
      novel cardiovascular disease risk factor. This review outlines what is known
      about the association of 25-hydroxyvitamin D levels and cardiovascular disease
      risk. RECENT FINDINGS: Low 25-hydroxyvitamin D levels have been associated with
      the cardiovascular disease risk factors of hypertension, obesity, diabetes
      mellitus and the metabolic syndrome, as well as cardiovascular disease events
      including stroke and congestive heart failure. Studies suggest vitamin D
      deficiency may be a contributor to the development of cardiovascular disease
      potentially through associations with diabetes or hypertension. SUMMARY: Vitamin
      D deficiency is easy to screen for and easy to treat with supplementation.
      Further larger observational studies and randomized clinical trials are, however,
      needed to determine whether vitamin D supplementation could have any potential
      benefit in reducing future cardiovascular disease events and mortality risk.

PMID- 18090652
TI  - The inflammatory status of old age can be nurtured from the intestinal
      environment.
AB  - PURPOSE OF REVIEW: Recent studies suggest an association between inflammation
      status and the presence of chronic disease in the elderly. The review examines
      publications that address the low level of chronic inflammation and emphasizes
      how an altered host-microbiota interaction at the gut level could contribute to
      maintaining a low systemic inflammatory status in the elderly. RECENT FINDINGS:
      The first population cross-sectional studies with relevant numbers of healthy
      elderlies show age-related global changes in gut microbiota with a consistent
      increase in nonpathogenic Gram-negative mainly Enterobacteria and country
      specific changes in bifidobacteria. Noninvasive methods have permitted us to
      detect subclinical intestinal inflammation in the elderly population.
      Furthermore, few studies report on immune and/or inflammatory response; however,
      prebiotics, probiotics or synbiotics might improve the inflammatory condition of
      the elderly. SUMMARY: A better understanding of the mechanisms of host-gut
      microbiota cross-talk would significantly help in the design of novel nutritional
      strategies targeting immune reactivity at the mucosal level.

PMID- 18090653
TI  - Age, alcohol metabolism and liver disease.
AB  - PURPOSE OF REVIEW: Alcohol consumption among the elderly has increased. Alcohol
      metabolism changes with age and the elderly are more sensitive to the toxic
      effects; this increased consumption is therefore of great clinical relevance.
      RECENT FINDINGS: Metabolism of ethanol changes with advancing age because
      activity of the enzymes involved, such as alcohol and acetaldehyde dehydrogenase
      and cytochrome P-4502E1, diminish with age. The water distribution volume also
      decreases with age. Both lead to increased blood concentrations of ethanol. Also,
      elderly people take more drugs, and ethanol and these drugs may interact;
      therefore, alcohol consumption can modify serum drug concentrations and their
      toxicity. Finally, elderly people may suffer more frequently from other types of
      liver disease, and alcohol may exacerbate these. SUMMARY: Over recent decades
      alcohol consumption has increased among those who are older than 65 years.
      Alcohol is more toxic in the ageing organism because of changes in its
      metabolism, distribution and elimination, which lead to central nervous system
      effects at lower levels of intake; also, ageing organs such as brain and liver
      are more sensitive to the toxicity of alcohol. For these reasons, alcohol should
      be used in moderation, especially among those of older age.

PMID- 18090654
TI  - Individualizing recommendations for weight management in the elderly.
AB  - PURPOSE OF REVIEW: This review provides current strategies for weight management
      in the elderly population as it can be different from young adults due to
      multiple factors: co-morbidities, polypharmacy, limitation of functional
      activities, social issues. RECENT FINDINGS: The recommendations for weight
      management for all age groups include exercise, diet, pharmacotherapy and
      surgery. In the elderly population, because of changes in age-related body
      composition, reduced energy requirement and expenditure, the standard young adult
      recommendations cannot be applied directly. The goal of weight management in the
      elderly differs from the young adult. The preferred method is maintenance of
      weight rather than aggressive weight loss with achieving a healthy, functional,
      and good quality of life. SUMMARY: The growing prevalence of obesity in the
      elderly population is becoming a major health problem and can affect functional
      status, can contribute to frailty and decline in activity, as well as worsening
      co-morbid medical problems. Practical recommendations for weight management in
      the elderly are challenging because of the obesity paradox in the elderly, and
      the lack of substantial research in this population. Individualized
      recommendations should be considered for elderly patients with a focus on the
      underlying medical problems, functional status and living environments.

PMID- 18090655
TI  - Skeletal muscle gain: how much can be achieved by protein and amino acid
      administration?

PMID- 18090656
TI  - Individual amino acid requirements in humans: an update.
AB  - PURPOSE OF REVIEW: To discuss recent amino acid requirement studies in adult
      humans and school-age children, primarily determined using the indicator amino
      acid oxidation technique. RECENT FINDINGS: Using the minimally invasive indicator
      amino acid oxidation model, requirements for most indispensable amino acids have
      been defined in adult humans. The estimates are comparable to the values obtained
      using the more elaborate 24-h indicator amino acid oxidation and balance model.
      The less-invasive indicator amino acid oxidation model has also been successfully
      applied to define requirements in healthy school-age children and children with
      disease. A recent adaptation of the indicator amino acid oxidation method to
      determine protein requirements in adult humans resulted in mean and safe values
      of 0.93 and 1.2 g protein/kg/day, respectively. These estimates are 40-50% higher
      than current recommendations and suggest an urgent need to reassess
      recommendations for protein intake in humans. SUMMARY: In summary, indicator
      amino acid oxidation is a robust technique, and has resulted in the definition of
      amino acid and protein requirements in adult humans and children. A wider
      application of the technique in other vulnerable populations across life stages
      and in other diseases is now possible.

PMID- 18090657
TI  - Effect of whey protein isolate on strength, body composition and muscle
      hypertrophy during resistance training.
AB  - PURPOSE OF REVIEW: Sarcopenia (skeletal muscle wasting with aging) is thought to
      underlie a number of serious age-related health issues. While it may be seen as
      inevitable, decreasing this gradual loss of muscle is vital for healthy aging.
      Thus, it is imperative to investigate exercise and nutrition-based strategies
      designed to build a reservoir of muscle mass as early as possible. RECENT
      FINDINGS: Elderly individuals are still able to respond to both resistance
      training and the anabolic signals provided by protein ingestion, provided
      specific amino acids, such as leucine, are present. Whey proteins are a rich
      source of these essential amino acids and rapidly elevate plasma amino acids,
      thus providing the foundations for preservation of muscle mass. Several studies
      involving supplementation with whey protein have been shown to be effective in
      augmenting the effects of resistance exercise, particularly when supplementation
      occurs in the hours surrounding the exercise training. SUMMARY: While further
      work is required, particularly in elderly people, simple dietary and exercise
      strategies that may improve the maintenance of skeletal muscle mass will likely
      result in a decrease in the overall burden of a number of diseases and improve
      the quality of life as we age.

PMID- 18090659
TI  - Growth hormone, arginine and exercise.
AB  - PURPOSE OF REVIEW: To describe the effect of an acute bout of exercise on growth
      hormone responses and to discuss the effect of L-arginine supplementation on
      growth hormone responses. RECENT FINDINGS: Recent studies have shown that resting
      growth hormone responses increase with oral ingestion of L-arginine and the dose
      range is 5-9 g of arginine. Within this range there is a dose-dependent increase
      and higher doses are not well tolerated. Most studies using oral arginine have
      shown that arginine alone increases the resting growth hormone levels at least
      100%, while exercise can increase growth hormone levels by 300-500%. The
      combination of oral arginine plus exercise attenuates the growth hormone
      response, however, and only increases growth hormone levels by around 200%
      compared to resting levels. SUMMARY: Exercise is a very potent stimulator of
      growth hormone release and there is considerable research documenting the
      dramatic growth hormone rise. At rest oral L-arginine ingestion will enhance the
      growth hormone response and the combination of arginine plus exercise increases
      growth hormone, but this increase may be less than seen with exercise alone. This
      diminished response is seen in both in both younger and older individuals.

PMID- 18090658
TI  - Amino acid metabolism and regulatory effects in aging.
AB  - PURPOSE OF REVIEW: To examine recent discoveries related to the amino acid
      metabolism and regulatory effects in aging, focusing on the development and
      treatment of age-related muscle loss (sarcopenia). RECENT FINDINGS: While basal
      amino acid metabolism may be unaffected by age, elderly subjects appear to have a
      decreased ability to respond to anabolic stimuli such as insulin and, to a lesser
      extent, amino acids. Specifically, compared to young subjects, the stimulation of
      muscle protein synthesis is attenuated in elderly subjects following the
      administration of mixed meals due to insulin resistance. In addition, the
      anabolic effect of amino acids appears blunted at low doses. Recent studies,
      however, have highlighted that these age-related alterations in amino acid
      metabolism may be overcome by provision of excess leucine, changes in the daily
      protein intake pattern or exercise, which improve activation of translation
      initiation and muscle protein synthesis. SUMMARY: Muscle loss with aging is
      associated with significant changes in amino acid metabolism, which can be
      acutely reversed using nutritional manipulations and exercise. Long-term, large
      clinical trials are, however, needed to determine the clinical significance of
      these findings in the elderly population, and to establish if nutritional and
      exercise interventions can help prevent and treat sarcopenia.

PMID- 18090661
TI  - Bibliography. Current world literature. Ageing: biology and nutrition.

PMID- 18090660
TI  - L-Arginine therapy in cardiovascular pathologies: beneficial or dangerous?
AB  - PURPOSE OF REVIEW: L-Arginine is the precursor for nitric oxide synthesis. In the
      brain, nitric oxide acts as a neurotransmitter; in the immune system, nitric
      oxide acts as a mediator of host defense; in the cardiovascular system, nitric
      oxide mediates the protective effects of the intact endothelium, acting as an
      endogenous antiatherogenic molecule. RECENT FINDINGS: About 5 g of L-arginine is
      taken up each day. L-Arginine plasma levels are not significantly reduced in most
      diseases, except end-stage renal failure during hemodialysis treatment.
      Nonetheless, intravenous or oral administration of L-arginine results in enhanced
      nitric oxide elaboration in subjects with impaired endothelial function. In
      clinical trials short to medium-term administration of L-arginine improved the
      symptoms of cardiovascular disease. In other trials, however, L-arginine was not
      beneficial and in one recent long-term study higher mortality of subjects
      receiving L-arginine than those receiving placebo was reported. These
      contradictory results were not understood for a long time. The endogenous
      inhibitor of nitric oxide synthase, asymmetric dimethylarginine, may determine a
      subject's response to L-arginine. L-Arginine appears to exert no effect in
      subjects with low asymmetric dimethylarginine levels, whereas in subjects with
      high asymmetric dimethylarginine levels L-arginine restores the L
      arginine/asymmetric dimethylarginine ratio to normal and normalizes endothelial
      function. SUMMARY: The effects of L-arginine supplementation on human physiology
      appear to be multicausal and dose related. Criteria need to be developed to
      define patients who benefit from L-arginine supplementation.

PMID- 18090662
TI  - Bibliography. Current world literature. Hormones, autacoids, neurotransmitters
      and growth factors.

PMID- 18090663
TI  - Role of the endocannabinoid system in metabolic control.
AB  - PURPOSE OF REVIEW: Growing evidence suggests an important role in metabolic
      control of the endocannabinoid system, which is composed of cannabinoid
      receptors, endocannabinoids, and related enzymes. In this short review, we
      describe the latest advances in this research field, including the antiobesity
      effect of the cannabinoid receptor CB1 antagonist rimonabant and the anorexic
      effect of N-oleoylethanolamine, an endocannabinoid-related, endogenous substance.
      RECENT FINDINGS: CB1 is expressed not only in various brain regions, including
      hypothalamus, but also in peripheral organs such as adipose tissue and liver. The
      endocannabinoid system appears to function as a physiological system regulating
      food intake, energy balance, and lipid metabolism through both central and
      peripheral mechanisms. Obesity may be associated with hyperactivity of the
      endocannabinoid system. Large phase III trials of rimonabant confirmed
      significant weight loss and waist circumference reduction in overweight and obese
      patients. The levels of HDL-cholesterol, triglycerides, and HbA1c were also
      improved. The anorexic effect of N-oleoylethanolamine was suggested to be
      mediated by peroxisome proliferator-activated receptor-alpha and the G protein
      coupled receptor GPR119. SUMMARY: These results highlight the importance of an
      endocannabinoid tone in metabolic control and therapeutic usefulness of CB1
      antagonists. Derivatives of N-oleoylethanolamine may be developed as new
      antiobesity drugs.

PMID- 18090664
TI  - Genetically altered animals in the study of the metabolic functions of peptide
      hormone systems.
AB  - PURPOSE OF REVIEW: Here we review the use of genetically altered animals to
      address the roles of peptide hormone systems in the modulation of energy
      homeostasis. Despite the disseminated use of transgenic techniques to establish
      the functional relevance of several peptide hormone systems, we focus on two
      multifunctional systems, the renin-angiotensin and the kallikrein-kinin systems.
      Initially, we explored the background information supporting the functional
      aspects of these systems, followed by novel knowledge obtained with the
      phenotypic characterization of genetically altered animals. RECENT FINDINGS: A
      role for the renin-angiotensin system in the regulation of adiposity and glucose
      metabolism has been suggested. Studies using genetically altered animals not only
      confirmed the physiological relevance of angiotensin II in the control of energy
      homeostasis, but also revealed that the adipose tissue renin-angiotensin system
      participates in the endocrine modulation of cardiovascular and renal function. On
      the other hand, the involvement of the kallikrein-kinin system with metabolic
      processes was not so obvious. Recent reports using genetically altered animals,
      however, provided strong evidence to support an important role for kinins in the
      control of glucose homeostasis and energy balance. SUMMARY: Here we present
      examples of how genetically altered animals contribute to a final postulation of
      the physiological roles of certain hormone systems, bringing new insights into
      the field.

PMID- 18090665
TI  - The interaction of pendrin and the epithelial sodium channel in blood pressure
      regulation.
AB  - PURPOSE OF REVIEW: This review summarizes the contribution of the Cl-/HCO3-
      exchanger pendrin in the renal regulation of blood pressure. RECENT FINDINGS:
      Intercalated cells are found in the distal convoluted tubule, the connecting
      tubule and the collecting duct. These cells regulate acid-base balance by
      secreting or absorbing OH-/H- equivalents and regulate vascular volume and blood
      pressure by absorbing chloride ions. In type B and non-A, non-B intercalated
      cells chloride absorption and HCO3- secretion are accomplished through the apical
      sodium-independent Cl-/HCO3- exchanger pendrin. With increased circulating
      aldosterone, pendrin abundance and transport are upregulated. In the absence of
      functional pendrin (Slc26a4 (-/-) mice), aldosterone-stimulated chloride
      absorption is reduced, which attenuates the blood pressure response to this
      steroid hormone. Pendrin also regulates aldosterone-induced changes in epithelial
      sodium channel abundance and function through a kidney-specific mechanism that
      does not involve changes in concentration of a circulating hormone. In vitro,
      angiotensin II increases sodium chloride absorption in the collecting duct by
      increasing the driving force for pendrin-mediated chloride absorption and the
      epithelial sodium channel-mediated sodium absorption through greater electrogenic
      hydrogen secretion. SUMMARY: Aldosterone and angiotensin II modulate the renal
      regulation of blood pressure, in part, by regulating pendrin-mediated chloride
      absorption and the epithelial sodium channel-mediated sodium absorption. Pendrin
      also modulates stimulation of the epithelial sodium channel by aldosterone.

PMID- 18090666
TI  - Role of fat mass and adipokines in chronic kidney disease.
AB  - PURPOSE OF REVIEW: As traditional risk factors cannot alone explain the high
      prevalence and incidence of cardiovascular disease in chronic kidney disease, the
      complex of insulin resistance, oxidative stress, and endothelial dysfunction has
      increasingly been studied as an important non-traditional risk factor. Recent
      studies show that the adipose tissue is a complex organ with pleiotropic
      functions far beyond the mere storage of energy. Fat tissue secretes a number of
      adipokines including leptin and adiponectin, as well as cytokines, such as
      resistin, visfatin, tumor-necrosis factor-alpha and interleukin-6. RECENT
      FINDINGS: Adipokine serum levels are markedly elevated in chronic kidney disease,
      likely due to a decreased renal excretion. Evidence suggests that these
      pluripotent signaling molecules may have multiple effects modulating insulin
      signaling, endothelial health and vascular outcome. SUMMARY: Fat tissue is a
      storage depot for energy and a source of circulating signaling molecules. It
      plays an important role in the catabolic uremic milieu, and has been linked to
      systemic inflammation and uremic anorexia. Further research is needed to
      investigate the complex interactions between adipokine signaling networks and its
      effects on vascular health and outcome in chronic kidney disease.

PMID- 18090667
TI  - The podocyte and diabetes mellitus: is the podocyte the key to the origins of
      diabetic nephropathy?
AB  - PURPOSE OF REVIEW: Podocyte injury plays a key role in the development of
      diabetic nephropathy. This review discusses recent advances in our understanding
      of mechanisms of podocyte injury in diabetes mellitus and the associated
      alterations in the function of the glomerular filtration barrier. RECENT
      FINDINGS: The effects of hyperglycemia on critical podocyte parameters including
      cell-cell interactions, attachment to the glomerular basement membrane, and
      podocyte apoptosis have been determined in both cell culture and in-vivo models
      of diabetes mellitus. The podocyte has also been identified as a target of action
      for insulin and growth hormone, hormones with significant roles in the altered
      homeostasis of diabetes mellitus. SUMMARY: Understanding the cellular and
      molecular basis for changes in podocyte structure and function in diabetes
      mellitus may lead to novel diagnostic tools and treatment strategies for diabetic
      nephropathy.

PMID- 18090669
TI  - Aldosterone and progression of renal disease.
AB  - PURPOSE OF REVIEW: The aim of this review is to look at the role of aldosterone
      in the progression of chronic kidney disease. The reduction of blood pressure and
      proteinuria in patients suffering from chronic kidney disease decreases the rate
      of disease progression. Suppression of angiotensin formation by angiotensin
      converting enzyme inhibitors and blockade of the angiotensin II receptor by
      angiotensin II type 1 antagonists are powerful therapeutic strategies that
      effectively lower blood pressure and slow the progression of renal disease. These
      therapies, however, provide only imperfect protection, since they cannot always
      prevent endstage renal failure. RECENT FINDINGS: Aldosterone plays a significant
      role in the pathogenesis of arterial hypertension and renal disease. Angiotensin
      converting enzyme inhibitors and angiotensin II type 1 antagonists are incomplete
      in suppressing aldosterone production and 'aldosterone breakthrough' can be
      observed under continued treatment. Aldosterone blockade reduces blood pressure
      in virtually all patients with hypertension. In proteinuric patients, the
      addition of an aldosterone antagonist to an angiotensin converting enzyme
      inhibitor or to angiotensin II type 1 antagonists reduces proteinuria. SUMMARY:
      The use of aldosterone antagonists in addition to either angiotensin converting
      enzyme inhibitors or angiotensin II type 1 antagonists in proteinuric patients
      reduces proteinuria, which may translate into preservation of the glomerular
      filtration rate in the longer term. Therefore, blockade of the aldosterone
      pathway may prove to be a beneficial therapy for chronic kidney disease.

PMID- 18090668
TI  - Nuclear factor-kappaB as a hormonal intracellular signaling molecule: focus on
      angiotensin II-induced cardiovascular and renal injury.
AB  - PURPOSE OF REVIEW: Nuclear factor-kappaB (NF-kappaB) has recently emerged as a
      novel intracellular signaling molecule for hormones, cytokines, chemokines, and
      growth factors. The purpose of this article is to highlight the role of NF-kappaB
      as an intracellular signaling for angiotensin II and clinical perspectives of
      targeting NF-kappaB signaling in treating hypertensive and renal diseases. RECENT
      FINDINGS: A selective review of recently published work provides strong evidence
      that activation of NF-kappaB signaling by angiotensin II mediates the detrimental
      effects of angiotensin II on the transcription of cytokines, chemokines and
      growth factors. Angiotensin II stimulates AT1 receptors to activate NF-kappaB
      signaling via both canonical (classical) and noncanonical (alternative) pathways.
      Intracellular angiotensin II may also induce NF-kappaB activation and
      transactivation of target genes. Nearly 800 NF-kappaB inhibitors have been
      described, but none has advanced to clinical trials. However, angiotensin
      converting enzyme inhibitors and AT1 blockers are beneficial in treating
      angiotensin II-induced hypertensive and renal injury in part by inhibiting NF
      kappaB activation. SUMMARY: Angiotensin II induces the transcription of
      cytokines, chemokines and growth factors, leading to target organ injury. These
      responses to angiotensin II are caused primarily by AT1 receptor-activated NF
      kappaB signaling. Targeting NF-kappaB signaling with angiotensin converting
      enzyme inhibitors, AT1 blockers, and specific NF-kappaB inhibitors may represent
      a novel approach in treating angiotensin II-induced hypertensive and renal
      diseases.

PMID- 18090670
TI  - The balance of angiotensin II and nitric oxide in kidney diseases.
AB  - PURPOSE OF REVIEW: The imbalances in the activities of various components of the
      neurohormonal system that maintain renal homeostasis may have important
      implications in pathophysiology. This review aims to examine the evidence for
      disparities between angiotensin II and nitric oxide in acute and chronic kidney
      diseases. RECENT FINDINGS: Low nitric oxide generation and activity characterize
      chronic kidney disease, whereas decreasing angiotensin activity is known to be
      beneficial. High oxygen consumption and hypoxia are thought to play important
      roles in progression of kidney disease, and angiotensin II and nitric oxide
      appear to influence oxygen consumption in these models. The common etiologic
      models of acute kidney injury, such as ischemia, nephrotoxic drug administration,
      radiocontrast exposure and sepsis, also demonstrate significant imbalances in the
      activities of angiotensin II and nitric oxide. SUMMARY: Disparities between the
      activities of angiotensin II and nitric oxide are pervasive in a variety of acute
      and chronic kidney diseases. A better understanding of these interactions and
      their net effect on renal pathophysiology can lead to therapeutic interventions
      aimed at preventing or correcting such imbalances.

PMID- 18090671
TI  - Targeting genes in the renin-angiotensin system.
AB  - PURPOSE OF REVIEW: The renin-angiotensin system plays a key role in the
      regulation of blood pressure and fluid homeostasis. Owing to its critical
      contribution to blood pressure control, abnormalities of any component in this
      system can lead to hypertension and cardiovascular diseases. In this review, we
      will highlight studies using this approach to uncover new perspectives on the
      physiology of the renin-angiotensin system. RECENT FINDINGS: Over the past
      decade, application of techniques for manipulating the genome of living animals,
      including gene targeting through homologous recombination in embryonic stem
      cells, has provided unique insights into the complex biology of the renin
      angiotensin system. Along with advances in understanding functions of the
      classical components of the system, gene targeting has clarified the functions of
      newly discovered angiotensin-converting enzyme homologues. SUMMARY: Since
      pharmacological antagonists of the renin-angiotensin system are widely used in
      clinical medicine, advances in the gene-targeting experiments of the system have
      helped to clarify the mechanisms of action of these agents and may provide clues
      for improved approaches for the treatment of hypertension and kidney diseases.

PMID- 18090672
TI  - An update on cyclooxygenase-2 expression and metabolites in the kidney.
AB  - PURPOSE OF REVIEW: This review highlights recent studies examining the expression
      and function of cyclooxygenase-2 and its metabolites in the kidney. RECENT
      FINDINGS: Expression of cyclooxygenase-2 is regulated by both physiologic and
      pathophysiologic perturbations, with volume depletion upregulating macula-densa
      expression and volume expansion upregulating medullary expression. Macula densa
      cyclooxygenase-2 is a modulator of juxtaglomerular renin expression, and there is
      increasing evidence that cyclooxygenase-2 expression is modulated by multiple
      components of the renin-angiotensin system, including angiotensin II, through
      both AT1 and AT2 receptors. There are also indications that macula densa
      cyclooxygenase-2 expression may be regulated by the prorenin/renin receptor.
      Medullary cyclooxygenase-2 metabolites modulate salt and water excretion, and
      cyclooxygenase-2 inhibitors lead to sodium and volume retention and may raise
      blood pressure. There is also increasing evidence that cyclooxygenase-2
      expression increases in progressive renal injury. Given their cardiovascular and
      renal side effects, cyclooxygenase-2 inhibitors are not a feasible intervention
      for long-term therapy against progressive renal damage, but further delineation
      of the downstream receptors and synthases involved may provide therapeutic
      targets. SUMMARY: Recent studies have highlighted the important role that
      cyclooxygenase-2 metabolites play both in regulation of normal renal function and
      as potential mediators of acute and chronic renal injury.

PMID- 18090673
TI  - Endothelin and NOS1/nitric oxide signaling and regulation of sodium homeostasis.
AB  - PURPOSE OF REVIEW: In general, the nitric oxide and endothelin signaling pathways
      in the kidney promote natriuresis. The basis for this statement will first be
      reviewed for each of these systems. Next, this review will outline the
      progression of data providing support for our hypothesis that an intra-renal
      mechanism of endothelin activation of ETB receptors stimulates NOS1 activity and
      nitric oxide production to promote sodium excretion. RECENT FINDINGS: New
      information in recent years has provided considerable evidence that both nitric
      oxide and endothelin function to regulate sodium and water balance by the kidney.
      Furthermore, dysfunction of these pathways may play a role in salt-sensitivity
      and hypertension. While a strong picture has emerged to suggest these systems are
      important and powerful players in sodium homeostasis, many questions remain to be
      answered before we can apply these mechanisms to an understanding of clinical
      hypertension. SUMMARY: Salt-sensitive hypertension contributes to the growing
      population of patients resistant to conventional antihypertensive therapy. Thus,
      a thorough understanding of the mechanisms related to the control of sodium
      excretion will allow a more focused approach for future therapeutic studies.

PMID- 18090674
TI  - Is kidney injury a reversible process?
AB  - PURPOSE OF REVIEW: Recent evidence indicates that the progression of renal
      fibrosis is a reversible process in experimental models. This review summarizes
      the new insights concerning the mechanisms of progression and regression of renal
      disease and examines this novel evidence in the light of feasibility and transfer
      to human nephropathies. RECENT FINDINGS: Most of the studies investigated
      prevention rather than reversal of renal disease. Interesting results have been
      obtained using agents antagonizing the signaling pathway of transforming growth
      factor-beta, by blockers of the tyrosine kinase growth factor receptors and by
      kinin receptor activation. SUMMARY: The future for therapy belongs to systems
      that mediate simultaneously proliferation, fibrosis and inflammation. Inhibitors
      of this kind of mediator will provide valuable assistance to 'classical' therapy
      with angiotensin II blockers, in order to achieve regression of renal fibrosis
      and reversal of renal failure.

PMID- 18090675
TI  - Insight into the genetics of diabetic nephropathy through the study of mice.
AB  - PURPOSE OF REVIEW: To discuss mouse models of diabetic nephropathy and their use
      in discovering genetic risk factors predisposing to diabetic nephropathy. RECENT
      FINDINGS: Despite occurring in only 10-40% of diabetic patients, diabetic
      nephropathy is the largest single cause of end stage renal disease in the USA.
      Accumulated evidence points to critical genetic factors that predispose a subset
      of diabetic patients to nephropathy. Defining the genes that confer risk for
      nephropathy in human populations has proven challenging. The use of robust
      genetic reagents available in the laboratory mouse provides a complementary
      approach to defining genes that predispose to diabetic nephropathy in mice and
      humans. These findings support the existence of dominant mutations predisposing
      to diabetic nephropathy in mice as well as substantiating an important role for
      eNOS in forestalling the development of diabetic nephropathy. SUMMARY: When
      studied for a sufficient duration of diabetic hyperglycemia, some strains of mice
      exhibit changes similar to those of human diabetic nephropathy. The unique
      genetic reagents in mice should help accelerate the identification of genes
      predisposing to diabetic nephropathy.

PMID- 18090676
TI  - Renal hemodynamics in heart failure: implications for treatment.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe the hemodynamic
      alterations in the kidney which occur in heart failure and to understand the
      cardiovascular and renal mechanisms responsible for these alterations.
      Implications for the clinical management of heart failure will be delineated on
      the basis of the pathophysiologic cardiorenal interactions. RECENT FINDINGS:
      Recent studies have shown that patients with heart failure exhibit abnormal
      cardiorenal hemodynamics on the basis of numerous pathophysiologic disturbances
      involving both the cardiovascular and renal systems. Macrovascular stiffening
      leads to microvascular damage with impairment of renal autoregulation. Diffuse
      neurohormonal activation occurs of multiple systems, particularly the renin
      angiotensin-aldosterone system, sympathetic nervous system, arginine vasopressin
      system, endothelin system, and natriuretic peptide system, leading to an overall
      vasoconstrictive state promoting sodium and water retention and further
      impairment of cardiac function. Pharmacologic therapy directed at specific
      biochemical targets within these neurohormonal pathways has shown marked benefits
      in improving both the symptoms of heart failure and clinical outcomes. SUMMARY:
      Heart failure is characterized by abnormal cardiovascular hemodynamics, sodium
      and fluid retention, and diffuse neurohormonal activation, all of which affect
      the net renal hemodynamic state. An understanding of the pathophysiologic
      mechanisms is necessary to optimally manage patients with heart failure and help
      restore cardiorenal homeostasis.

PMID- 18090677
TI  - Vascular compliance and arterial calcification: impact on blood pressure
      reduction.
AB  - PURPOSE OF REVIEW: The aim of this article is to review the relationship between
      vascular calcification and difficult to control hypertension. This does not
      address antihypertensive treatment of drug resistant hypertension per se. RECENT
      FINDINGS: Vascular calcification occurs in a variety of common hypertension
      scenarios. Basic mechanisms of how and why vessels calcify are reviewed including
      new genetic insights. The potential for contributing to or improving
      calcification through drug therapies for nonhypertensive disorders is reviewed.
      SUMMARY: Vascular calcification is common and easily recognized. Studies that
      target its clinical consequences (arterial stiffness) as primary treatment goals
      are needed.

PMID- 18090679
TI  - Bibliography. Current world literature. Circulation and hemodynamics.

PMID- 18090678
TI  - Cardiovascular disease in dialysis patients: do some antihypertensive drugs have
      specific antioxidant effects or is it just blood pressure reduction? Does
      antioxidant treatment reduce the risk for cardiovascular disease?
AB  - PURPOSE OF REVIEW: Patients with end-stage renal disease have an extremely high
      cardiovascular disease mortality. Oxidative stress is one of the 'nontraditional'
      risk factors for cardiovascular disease mortality in dialysis patients. This
      review discusses antioxidant activity of the commonly prescribed antihypertensive
      agents and the effects of antioxidant interventions on cardiovascular disease
      mortality in patients with end-stage renal disease. RECENT FINDINGS: Several
      lines of evidence confirm antioxidant activity of the renin-angiotensin
      aldosterone antagonists, some of the calcium channel blockers, carvedilol, and
      hydralazine. This appears to be independent of their antihypertensive activity.
      Clinical evidence of their superiority in improving cardiovascular disease
      endpoints in end-stage renal disease, however, is lacking. There are no
      randomized trials that have examined the effect of correcting oxidative stress on
      clinical endpoints. One randomized study in patients on hemodialysis reported a
      reduction in oxidative stress and the plasma methylarginines with valsartan and
      amlodipine but no clinical endpoints were examined. SUMMARY: The effects of the
      antihypertensive agents with antioxidant activity on cardiovascular disease
      mortality in end-stage renal disease have not been examined in randomized
      clinical trials. These agents may offer specific clinical advantage in addition
      to lowering the blood pressure, but this remains to be proven. Two studies show a
      reduction in cardiovascular disease events with vitamin E and N-acetylcysteine in
      patients on hemodialysis without an effect on overall mortality.

PMID- 18090680
TI  - Prevalence and characteristics of immunomediated neuropathies in a group of
      patients with autoimmune diseases.
AB  - OBJECTIVE: To determine the prevalence and the clinical-neurophysiological
      characteristics of immunomediated peripheral neuropathies (PN) in a group of
      patients with systemic autoimmune diseases. METHOD: Fifty-nine patients with
      proved systemic autoimmune diseases were included. Patients underwent clinical
      examination and nerve conduction studies to diagnose the PN. RESULTS: Immune PNs
      were detected in 18 patients (30.5%). Out of the total number of PNs (18), 39%
      were sensory-motor polyneuropathies, 33% mononeuritis multiplex, 11% pure sensory
      polyneuropathies, 11% cranial neuropathies, and 6% proximal motor neuropathies,
      such as the Guillain-Barre syndrome. Nine PNs (50%) appeared at the onset of the
      connective tissue disorders, and the rest of the cases appeared during the course
      of the disease. Of the total of PNs detected in this study, only 45% had a
      previous diagnosis. Vasculitis was the disease that presented more associated
      PNs. Systemic lupus erythematosus showed the widest range of PN clinical
      varieties. CONCLUSIONS: The first national prevalence rate of PNs in patients
      with systemic autoimmune diseases was provided: 30.5%. No comparative data were
      found in the international bibliography. Sensory-motor polyneuropathy was the
      most frequently observed form of PN, followed by mononeuritis multiplex. The NPs
      appeared with the same frequency both at the onset and during the course of the
      diseases under study; these predominated at the onset of vasculitis and primary
      Sjogren syndrome. The compromise of the peripheral nervous system is
      underdiagnosed.

PMID- 18090681
TI  - Hyperestrogenemia simulating kennedy disease.
AB  - A 71-year-old man developed clinical signs of Kennedy disease including
      dysarthria, dysphagia, palatal and oral mandibular fasciculations, lower
      extremity weakness, gynecomastia, and testicular atrophy. Electrophysiologic
      studies showed sensory axonal polyneuropathy and chronic neurogenic changes of
      large-motor unit action potentials with decreased recruitment. Genetic analysis
      showed a normal 17-CAG repeat sequence. Laboratory studies showed an increased
      estrogen level of 180 to 220 pg/mL, probably related to his alcoholic fatty liver
      disease. Splenomegaly was present by ultrasound. The increased level of estrogen
      adversely affected estrogen-sensitive cells in breast, testicular, neuronal, and
      muscle cells, leading to the clinical phenotype.

PMID- 18090682
TI  - Neuromuscular involvement in nephrogenic systemic fibrosis.
AB  - INTRODUCTION: Nephrogenic fibrosing dermopathy causes fibrotic skin changes in
      the setting of renal failure. Although this condition was initially felt to be
      limited to the skin, recent studies have described widespread involvement, and
      the term nephrogenic systemic fibrosis (NSF) has been suggested. OBJECTIVE: To
      describe the clinical, electrophysiologic, and pathologic findings in three NSF
      patients with neuromuscular involvement. METHODS: Case report. RESULTS: Three
      patients developed progressive hardening of the skin and underlying fascia and
      muscles. Strength was difficult to assess because of limited joint mobility.
      electromyography/nerve conduction studies suggested involvement of both nerve and
      muscle. Muscle biopsy demonstrated primarily myopathic changes with variable
      fibrosis. CONCLUSION: Neuromuscular involvement occurs in NSF and may be
      difficult to appreciate clinically because of joint and skin fibrosis.

PMID- 18090683
TI  - HIV infection presenting with motor axonal variant of Guillain-Barre Syndrome.
AB  - OBJECTIVES: We present a case of acute motor axonal neuropathy in a patient with
      previously unrecognized human immunodeficiency virus (HIV) infection. METHODS: A
      46-year-old male graduate student from Mali, Africa presented with a 3-week
      history of progressive weakness that began during a visit home from Utah. The
      symptoms stabilized by 6 weeks and gradually improved without treatment. RESULTS:
      Electrodiagnostic studies revealed widespread fibrillation potentials and
      positive sharp waves with normal sensory amplitudes and no demyelinating
      features. Cerebrospinal fluid pleocytosis and elevated protein prompted a test
      for HIV infection, which returned positive. CONCLUSIONS: To our knowledge, this
      is the first case of acute motor axonal neuropathy in HIV outside of a
      seroconversion reaction.

PMID- 18090684
TI  - Anatomical localization of motor endplate bands in the human biceps brachii.
AB  - OBJECTIVES: : Botulinum neurotoxin (BoNT) reduces disabling muscle contraction in
      numerous disorders with muscle overactivity. While motor endplates are the
      primary site of action for BoNT, their location is unknown in most human muscles.
      This study localized the motor endplate bands (MEB) within human biceps brachii
      (BB) muscles in relation to external landmarks. METHODS: : Five human BB muscles
      were obtained from autopsy. Three muscles were processed for Sihler's stain, a
      nerve staining technique, and 2 were processed by whole-mount
      acetylcholinesterase stain. RESULTS: : The major MEB in BB is an inverted V
      shaped band, 1 cm in width, located 7 cm superior to the olecranon laterally, 11
      cm superior to the olecranon in the middle, and 8 cm above the olecranon
      medially. The ratio of MEB location to total olecranon-acromion length is 0.25 at
      the lateral edge, 0.39 in the midline, and 0.28 at the medial edge. CONCLUSIONS:
      : This study localized MEB in human BB in reference to external landmarks. This
      data should improve the feasibility of endplate targeting when injecting BoNT in
      BB, which might enhance the clinical efficacy of these injections.

PMID- 18090685
TI  - Unilateral thigh atrophy and weakness in hip osteoarthritis.
AB  - Osteoarthritis is a common condition that affects a significant percentage of
      people in the United States. The case and discussion will serve to introduce to
      the neurologist the issue of hip osteoarthritis causing thigh atrophy and
      weakness. The pathogeneses of muscular atrophy in the setting of osteoarthritis
      and of muscle weakness as a cause of osteoarthritis will be explored.

PMID- 18090686
TI  - Assessing quality of life in ALS.
AB  - The issue of quality of life is important for the patient with amyotrophic
      lateral sclerosis (ALS) and his or her family. Although initial thoughts
      frequently are that quality of life will be poor, there are strong data to
      support a relatively good quality of life despite the inexorable decline in
      strength and loss of function with disease progression. This article discusses
      how quality of life can be measured in ALS patients and caregivers, the results
      of studies, and factors affecting quality. It ends with 10 suggestions for
      clinicians who care for ALS patients and their caregivers.

PMID- 18090688
TI  - Electroconvulsive therapy: all in the family.

PMID- 18090689
TI  - What we learn about continuation treatments from the collaborative
      electroconvulsive therapy studies.

PMID- 18090690
TI  - Schizophrenia, osteoporosis, and an examination of the risk of fractures in
      patients receiving ECT.

PMID- 18090691
TI  - The history of Lipotmezo, the site of the first convulsive therapy.
AB  - The National Institute of Psychiatry and Neurology, better known as "Lipot,"
      where convulsive therapy was first performed by Laszlo Meduna in 1934, is an
      important site in the history of biological psychiatry. In the first half of the
      article, the circumstances regarding the foundation of the Institute and its
      first 60 years are reviewed. Meduna's achievements, the theoretical foundation of
      convulsive therapy, and its realization as an effective therapy are described.
      Finally, the latest 70 years of the Institute will be briefly reviewed, with
      special emphasis on the events of the last few months of 2007 in which the
      institution has been closed.

PMID- 18090692
TI  - Pacheco e Silva [corrected] and the origins of electroconvulsive therapy in
      Brazil. 1941.
AB  - There are few data about the history of electroconvulsive therapy (ECT) in many
      countries of the world, especially in developing ones as those of South America.
      This article offers a translation of an article published in 1941 by Dr Pacheco e
      Silva describing how ECT came to Brazil and its first use. He tells of how he
      learned about ECT during the 97th American Psychiatric Association Annual Meeting
      held in Richmond, Va, that same year, the lectures he attended, his visits to
      some American hospitals that were performing ECT at that time, the devices he
      bought, and his first experiences in using ECT in Brazil, first with dogs and,
      then, with patients. We also give a brief biography of Dr. Pacheco e Silva, who
      was a very important Brazilian psychiatrist.

PMID- 18090693
TI  - Regressive and intensive methods of electroconvulsive therapy: a brief historical
      note.
AB  - In the 1940s, regressive and intensive methods were developed to increase the
      therapeutic effects of electroconvulsive therapy. The diagnostic indications,
      methods of application, effectiveness, complications, and mortality of these
      techniques are briefly discussed here. An attempt is also made to evaluate the
      risks and benefits of these methods from a historical perspective.

PMID- 18090694
TI  - Maximal response to electroconvulsive therapy for the treatment of catatonic
      symptoms.
AB  - OBJECTIVES: Because the number of medical lawsuits has recently increased in
      Japan, doses of medication above the upper limits have recently been avoided,
      even when treating catatonic patients. We treated catatonic symptoms with drugs
      within the upper limit of dosage and electroconvulsive therapy (ECT) to determine
      the maximal response. METHODS: We examined 50 consecutive patients with catatonic
      symptoms admitted to a university hospital during a 32-month period who were
      treated with either drugs within the upper limit or ECT. RESULTS: Response rates
      were as follows: ECT, 100%; chlorpromazine, 68%; risperidone, 26%; haloperidol,
      16%; and benzodiazepines, 2%. CONCLUSIONS: The findings indicated that ECT is the
      treatment of choice for catatonic symptoms.

PMID- 18090695
TI  - Anesthesia outcomes in a randomized double-blind trial of sevoflurane and
      thiopental for induction of general anesthesia in electroconvulsive therapy.
AB  - The purpose of the study was to compare hemodynamics and postanesthetic
      tolerability of sevoflurane versus thiopental in electroconvulsive therapy (ECT).
      The design was a randomized double-blind trial in the ECT suite of a tertiary
      referral medical center. Thirty-one patients were randomized to either
      sevoflurane or thiopental induction of anesthesia for up to 6 of each subject's
      ECT treatments. Measurements included hemodynamics (heart rate and blood
      pressure), arrhythmias, posttreatment orientation, time to first breath, and
      posttreatment side effects. Sevoflurane compared favorably with thiopental in
      terms of hemodynamics and time to first breath, although there was a slightly
      nonsignificant trend toward faster recovery with sevoflurane. Sevoflurane was
      associated with significantly better postictal orientation 20 minutes after the
      treatment. We conclude that inhalational anesthesia with sevoflurane presents a
      well-tolerated alternative for ECT anesthesia.

PMID- 18090696
TI  - Propofol and methohexital as anesthetic agents for electroconvulsive therapy: a
      randomized, double-blind comparison of electroconvulsive therapy seizure quality,
      therapeutic efficacy, and cognitive performance.
AB  - BACKGROUND: Propofol is often used as an anesthetic agent for electroconvulsive
      therapy (ECT). Whether the relatively short seizure duration, resulting from the
      medication, deteriorates the seizure quality and therapeutic outcomes, or whether
      propofol might be associated with small but significant post-ECT cognitive
      impairments, is still a subject of controversy. The purpose of our study was to
      test these hypotheses in comparison with methohexital. MATERIALS AND METHODS: In
      a double-blind, controlled study, 50 patients with severe major depression who
      were to be treated with ECT were randomly assigned to anesthesia with propofol
      (120.9 +/- 50.0 mg) or methohexital (83 +/- 26.3 mg) and were observed for 2
      months. The 2 drugs were compared on the basis of electroencephalography
      registered seizure duration, mean blood pressure, as well as pulse frequency,
      seizure efficacy index, and postictal suppression. Systolic and diastolic blood
      pressure, and seizure duration and quality were recorded consecutively during ECT
      treatments. Changes in depressive symptoms and cognitive functions were measured
      at 5 time points, pre-ECT, after the third to fifth ECT, post-ECT treatment, and
      at a follow-up examination 2 and 8 weeks after the last ECT treatment. RESULTS:
      Patients on propofol showed a significantly lower increase in blood pressure post
      ECT (P < 0.001), their seizure duration was comparable to patients on
      methohexital (P = 0.072), and seizure quality was significantly superior, as was
      measured by the Postictal Suppression Index (P = 0.020), and comparable to the
      methohexital group as measured by the Seizure Efficacy Index (P = 0.160). The
      improvement of depressive symptoms and the improvement in cognitive functions
      were similar in both groups (with the exception of the results from 2 cognition
      tests). CONCLUSIONS: Propofol, as compared with methohexital, results in a more
      moderate increase in blood pressure and shorter seizure duration. The seizure
      quality did not differ significantly between the 2 groups. We detected a tendency
      toward improved cognitive performance after anesthesia with propofol as compared
      with methohexital, but with statistical significance in only 2 cognition trials.
      Therefore, propofol is a safe and efficacious anesthetic for ECT treatment.

PMID- 18090697
TI  - Data management and design issues in an unmasked randomized trial of
      electroconvulsive therapy for relapse prevention of severe depression: the
      consortium for research in electroconvulsive therapy trial.
AB  - BACKGROUND: The use of double-blind designs, normally the criterion standard of
      clinical trials, is impossible when comparing medication therapy to procedural
      therapies for depression. In the Consortium for Research in Electroconvulsive
      Therapy (CORE) trial, depressed patients recently remitted with electroconvulsive
      therapy (ECT) were randomly assigned to receive continuation therapy with either
      ECT or medications. The purpose of this article is to describe the design
      characteristics and challenges of the trial and of our method of dealing with the
      lack of double-blind outcome assessment. METHODS: The primary outcome measure was
      time to relapse of depression in the continuation phase. We developed a method to
      achieve partial blinding of depressive severity assessment. This consisted of
      videotaping the structured interviews, having the video tapes co-rated by
      personnel not involved in the patient's care, and a videotape-tracking maneuver
      so that the assessor of the videotapes could be blinded to phase and type of
      treatment. RESULTS: We enrolled 624 patients into the initial treatment phase of
      the trial. Of these, 201 met criteria for randomization into the second,
      continuation phase. Our videotape-tracking maneuver to reduce bias in outcome
      assessment worked well during the trial. CONCLUSIONS: The CORE study is the first
      multicenter, randomized controlled trial of continuation ECT in the relapse
      prevention of major depressive episodes. We successfully recruited a large number
      of severely depressed patients into a 6 month trial and used a method of reducing
      bias that might result from lack of blinding.

PMID- 18090698
TI  - Nurses' knowledge of and attitude to electroconvulsive therapy.
AB  - The relationship between the nurse and patient is usually close. The nature of
      nursing means that nurses spend more hours with patients than other health care
      professionals. Therefore, nurses' knowledge of and attitude to electroconvulsive
      therapy (ECT) is important because it is likely formed through close contact with
      patients; conversely, nurses' knowledge and attitudes will be conveyed to
      patients. There have been several studies exploring the topic of nurses'
      knowledge of and attitudes to ECT, but results are contradictory. OBJECTIVES: To
      explore nurses' knowledge of and attitude to ECT and to find whether knowledge
      and experience of ECT correlated with more positive attitudes to the treatment.
      METHOD: This was a questionnaire study including 211 registered and student
      nurses working in a London Mental Health Trust. It included knowledge and
      attitude scales and questions about experience and demography. RESULTS: There was
      a highly significant correlation between knowledge of and more positive attitudes
      to ECT. The more years in mental health, higher grade, and the greater number of
      patients undergoing ECT they had had contact with correlated with more knowledge.
      The number of patients they had had contact with and the closeness of that
      contact correlated with more positive attitudes. Registered nurses had more
      knowledge and more positive attitudes than student nurses. CONCLUSION: The
      relationship between attitudes and knowledge is complex. However, for nurses to
      provide appropriate support to patients undergoing ECT, they need to gain
      knowledge and experience of the therapy early in their careers.

PMID- 18090699
TI  - Patients' and their relatives' attitudes toward electroconvulsive therapy in
      bipolar disorder.
AB  - Although electroconvulsive therapy (ECT) is a safe and efficacious treatment,
      there is a widespread negative view of ECT in public and professional circles.
      Previous studies that reported psychiatric patients' and their relatives'
      feelings and attitudes toward ECT revealed generally positive results. However,
      there are no data focusing on bipolar patients' and their relatives' attitudes
      toward ECT. In this study, the perspectives of 70 bipolar patients and their 70
      relatives were examined before ECT. The study showed that the majority of
      patients and relatives believed they had not received adequate information about
      ECT, but they were satisfied with the treatment, found it beneficial, and
      maintained a positive attitude toward its use. The most commonly reported side
      effect was memory impairment. This is the first study focusing on bipolar
      patients' and their relatives' attitudes toward ECT in the literature.

PMID- 18090700
TI  - Knowledge of and attitudes toward electroconvulsive therapy of medical students
      in the United kingdom, Egypt, and Iraq: a transcultural perspective.
AB  - OBJECTIVES: To investigate the knowledge of and attitudes toward
      electroconvulsive therapy (ECT) in 3 samples of medical students from Iraq,
      Egypt, and the United Kingdom, respectively. MATERIALS AND METHODS: Medical
      students from Baghdad, Iraq, Cairo, Egypt, and Sheffield, United Kingdom medical
      schools completed a self-administered questionnaire including item of factual
      knowledge and of attitudes toward ECT. The Iraqi and Egyptian students were in
      their final year. The United Kingdom students have just finished their
      psychiatric placements. RESULTS: A total of 339 students responded (181 from
      Iraq, 85 from Egypt, and 73 from the United Kingdom). The theoretical knowledge
      base of the Iraqi sample was found to be better than that of the other 2 samples.
      Overall, the knowledge of ECT was not good especially in the Egyptian sample,
      where nearly two thirds were unable to mention any indication or side effect, and
      only 3.5% of them had the chance to observe ECT. The United Kingdom sample showed
      very positive attitudes (no one said that psychiatrists abuse ECT, and only 4%
      thought that ECT is a cruel treatment), followed by the Iraqi and the Egyptian
      samples. CONCLUSIONS: Different teaching styles and possibly some cultural
      factors affect the knowledge base of and the attitudes toward ECT. Finishing a
      psychiatric placement might have led to the very positive attitudes in the United
      Kingdom sample. Ensuring that medical students from the other 2 samples should
      observe ECT might improve their attitudes. A specific lecture about ECT would
      improve the knowledge of the 3 samples.

PMID- 18090701
TI  - Metabolic correlates of antidepressant and antipsychotic response in patients
      with psychotic depression undergoing electroconvulsive therapy.
AB  - OBJECTIVES: Although electroconvulsive therapy (ECT) is a very effective
      treatment of depression and psychosis, the mechanisms by which this occurs are
      not fully delineated. The objective of this study was to investigate the
      functional alterations in brain metabolism in response to ECT through the use of
      positron emission tomography assessment of cerebral glucose metabolism before and
      after a course of ECT. METHODS: Ten subjects with psychotic depression were
      studied with positron emission tomography using [F]fluorodeoxyglucose before and
      between 2 and 3 weeks after a course of ECT. Statistical parametric mapping and
      region of interest analyses of the anterior cingulate cortex (ACC) subregions
      (dorsal, rostral, subcallosal, and subgenual) and hippocampus were used to
      determine glucose metabolic changes from ECT. The Hamilton Depression Rating
      Scale and the Scale for Assessing Positive Symptoms were the primary measures
      used for assessing clinical changes from ECT. RESULTS: Electroconvulsive therapy
      led to significant increases in the left subgenual ACC and hippocampal
      metabolism, which were directly correlated with each other and to a reduction in
      depression as measured by total Hamilton Depression Rating Scale scores. Better
      antidepressant responders had increased, whereas poorer responders had a
      decreased left subgenual ACC and hippocampal metabolism. The decrease in positive
      symptoms was also correlated with increased left hippocampal metabolism.
      CONCLUSIONS: The antidepressant effect of ECT was correlated with increased
      metabolism in the left subgenual ACC and hippocampus, whereas the antipsychotic
      effect of ECT was only correlated with increased left hippocampal metabolism.
      This finding has implications to better understand the mechanism of
      antidepressant and antipsychotic effects of ECT.

PMID- 18090702
TI  - Long-term weekly continuation electroconvulsive therapy: a case series.
AB  - Despite best efforts with continuation pharmacotherapy, many patients relapse
      after a successful course of electroconvulsive therapy (ECT). Although
      maintenance ECT can be a useful and cost-effective treatment modality, there is
      considerable heterogeneity on how it is used. The authors report a case series of
      3 patients ages 68, 43, and 81 years with diagnosis of schizoaffective disorder,
      bipolar disorder, and major depression with psychotic features who required
      weekly ECT treatments for several years. All attempts to space treatments led to
      rapid decompensation. None of the patients experienced clinical evidence of any
      treatment related cognitive or physical morbidity.

PMID- 18090703
TI  - Neurobiological substrates of electroconvulsive therapy for Tourette syndrome: a
      Serial SISCOM study.
AB  - We report the case of an adult male patient with Tourette syndrome, self
      injurious behavior and depression, refractory to conventional treatment, and
      whose symptoms remitted after electroconvulsive therapy. Serial Technetium 99m
      Ethyl-Cysteinate-Dimer single photon emission tomographies were applied, before,
      during, and after electroconvulsive therapy. The neural substrates of this
      treatment process were further analyzed by woxel-wise subtracted single photon
      emission tomography images.

PMID- 18090704
TI  - A case of negative-pressure pulmonary edema after electroconvulsive therapy.
AB  - Pulmonary edema after electroconvulsive therapy (ECT) is a rarely reported
      condition that can result in serious morbidity and even death if not promptly
      recognized and treated. We report the case of 21-year-old man with FG syndrome
      and schizophrenia who developed negative-pressure pulmonary edema after his 28th
      ECT. The patient developed acute hypoxemia requiring positive-pressure
      ventilation and was observed overnight in the intensive care unit. He recovered
      fully and received 43 subsequent ECT treatments without complication. This case
      illustrates the importance of taking steps to prevent airway obstruction as well
      as recognizing this rare but serious complication.

PMID- 18090705
TI  - Catatonia complicated by pneumothorax successfully treated with electroconvulsive
      therapy.
AB  - We describe 2 patients with catatonia who developed the complication of
      pneumothorax, the accumulation of air in the pleural cavity leading to collapse
      of a lung. Electroconvulsive therapy was safely administered to resolve
      catatonia, with special attention to managing pneumothorax by insertion of a
      thoracostomy tube and careful management of ventilation.

PMID- 18090706
TI  - Respiratory failure secondary to malignant catatonia and klinefelter pulmonary
      deficits: successful electroconvulsive therapy.
AB  - Catatonia is a motor syndrome associated with disorders in behavior. Malignant
      catatonia (MC) is the form of acute catatonia dominated by fever and autonomic
      instability that may be fatal if inadequately treated. We present a case of MC
      complicated by respiratory failure in a patient with previously undiagnosed
      Klinefelter syndrome. Patients with Klinefelter syndrome have one or more extra X
      chromosome(s), and mental illness is a recognized association. The use of
      electroconvulsive therapy in these patients is well recognized, however, to our
      knowledge, this report is the first for MC in Klinefelter syndrome. We also
      describe, for the first time, type II respiratory failure as a secondary
      phenomenon occurring because of the combination of MC and thoracic abnormalities
      associated with Klinefelter syndrome. Interestingly, this is only the fourth
      reported case of respiratory failure due to any cause in MC. The positive outcome
      in this case confirms the efficacy of electroconvulsive therapy for MC and
      supports its safety for use in patients with Klinefelter syndrome and in those
      with secondary respiratory failure.

PMID- 18090707
TI  - Electroconvulsive therapy and antibiotics: a case report.
AB  - Infections are common comorbid conditions in hospitalized patients, including
      those receiving electroconvulsive therapy (ECT). In this report, we demonstrate
      the fluoroquinolone class of antibiotics can be associated with prolonged
      electroconvulsive seizure duration. We describe an 82-year-old woman treated with
      the fluoroquinolone, moxifloxacin, during a course of ECT. After previously
      tolerating ECT well, introduction of moxifloxacin for a respiratory tract
      infection was associated with prolonged seizure duration despite complete
      resolution of her respiratory complaint. Taken together with other evidence that
      fluoroquinolones lower seizure threshold, this report suggests fluoroquinolones
      should be avoided in patients receiving ECT.

PMID- 18090708
TI  - The successful use of electroconvulsive therapy in a patient with interferon
      induced psychotic depression.
AB  - We report the successful use of electroconvulsive therapy in a patient who
      developed major depression with psychotic features while being treated with
      interferon alfa-2b for hepatitis C. We reviewed the literature of similar cases
      and discuss treatment options for interferon-induced depression and psychosis.

PMID- 18090709
TI  - To restimulate or not in dose titration.

PMID- 18090710
TI  - Patients who inappropriately demand electroconvulsive therapy.

PMID- 18090711
TI  - Therapeutic hypothermia for global and focal ischemic brain injury--a cool way to
      improve neurologic outcomes.
AB  - BACKGROUND: Therapeutic hypothermia (TH) has been employed as a neuroprotective
      strategy for a wide array of clinical problems since the late 1940s. Animal
      studies have determined that the neuroprotective effect of hypothermia is
      pleiotropic, impacting many steps in both the ischemic cascade and reperfusion
      injury. Interest in the neuroprotective effects of TH for ischemic brain injury
      has been resurgent, fueled by both recent positive and negative clinical trials.
      A review of preclinical and clinical reports on TH in adult patients is provided
      in this article. REVIEW SUMMARY: Animal data and several large clinical studies
      of mild to moderate TH (32 degrees C-34 degrees C) for global cerebral ischemia
      describe favorable neurologic outcomes, with few adverse effects. However,
      clinical implementation for global ischemia remains poor. Some animal data
      support a role for TH in focal cerebral ischemia, if instituted soon after the
      onset of ischemia, and in the setting of reperfusion. Clinical studies of TH for
      focal cerebral ischemia have so far been equivocal. The available data suggest
      that, despite sharing some common components in the ischemic cascade, focal and
      global cerebral ischemia are pathophysiologically disparate, and may respond to
      different neuroprotective strategies. CONCLUSION: TH is a safe, effective
      neuroprotective strategy for global cerebral ischemia. Because of the
      neuroprotective efficacy of TH in adult comatose survivors of cardiac arrest,
      neurologists should advocate the implementation of this strategy. TH for focal
      ischemia is a promising therapeutic option, but requires more basic and clinical
      investigation.

PMID- 18090712
TI  - Recognizing and treating common psychiatric disorders in multiple sclerosis.
AB  - BACKGROUND: The rate of depression and other psychiatric disorders is greater in
      multiple sclerosis (MS) than in other chronic conditions or neurologic diseases.
      This means that clinical neurologists seeing MS patients will frequently be
      engaged in the diagnosis and treatment of psychiatric distress. REVIEW SUMMARY:
      This review provides a summary of what is known about psychiatric dysfunction in
      MS. It offers information about the current views on the link between various
      psychiatric disorders and MS. More important, it offers suggestions on how the
      knowledge from existing research can be integrated into real-world practice.
      CONCLUSION: Clinicians need to understand the factors that influence the
      development of psychiatric disorders in MS, the relationship between disease
      modifying therapies and psychiatric distress, and the issues surrounding the
      treatment of psychiatric conditions in MS. Thorough knowledge of psychiatric
      dysfunction and MS will allow the clinician to design an effective treatment
      regimen that helps patients cope with their disease.

PMID- 18090713
TI  - The immunogenicity of disease-modifying therapies for multiple sclerosis:
      clinical implications for neurologists.
AB  - BACKGROUND: Mounting a humoral response to foreign proteins is a normal function
      of immunity, but an undesirable outcome for protein-based therapeutic biologics.
      "Neutralizing antibodies" (NAbs) is the term given for antibodies against a
      biologic that reduce its bioavailability. Biologic therapeutics used to treat
      patients with multiple sclerosis (MS) have been associated with the risk of
      seroconversion to neutralizing antibody-positive status. Therefore, it is
      important to understand the causes of immunogenicity, methods for assessing
      antibody status, and the clinical impact of NAbs, particularly in patients who
      appear to be nonresponsive to treatment. REVIEW SUMMARY: Factors such as protein
      structure, contaminants, administration route, and patient characteristics affect
      immunogenicity of biologics used to treat MS. Binding assays and bioassays can be
      used for the detection and quantification of NAbs to these agents. Clinical
      studies have demonstrated that NAbs to interferon beta therapy develop between 3
      and 18 months after treatment initiation, and their presence affects treatment
      efficacy on clinical, imaging, and immunologic parameters. Binding antibodies to
      glatiramer acetate have been detected, but the clinical significance of these
      antibodies remains unclear. NAbs to natalizumab have also been identified and
      appear to at least partially abrogate the therapeutic response. CONCLUSION: When
      considering treatment options for patients with MS, the development of NAbs and
      their effects on clinical efficacy should be considered. Standardization of
      antibody assays and the development of guidelines for the management of patients
      with NAbs are important areas of future research.

PMID- 18090714
TI  - Neurological complications and aspects of basilar artery occlusive disease.
AB  - A recent case of basilar artery occlusion (BAO) in a 62-year-old woman is
      presented, along with a review of the literature on the clinical aspects of the
      disorder and treatment options. Therapeutic modalities such as intravenous and
      intra-arterial thrombolysis may significantly improve outcomes for patients with
      this disease.

PMID- 18090715
TI  - Cardiac arrest, mild therapeutic hypothermia, and unanticipated cerebral
      recovery.
AB  - OBJECTIVES: Animal and human studies support mild therapeutic hypothermia as an
      effective means of preventing brain injury in comatose patients resuscitated from
      cardiac arrest. However, there is little clinical experience with predicting
      neurologic outcome in this patient population. We present 4 comatose patients
      resuscitated from cardiac arrest treated with mild hypothermia whose in-hospital
      neurologic prognosis was determined by board-certified neurologists to be grave,
      yet were ultimately discharged from the hospital with no or minimal neurologic
      sequelae. RESULTS: We report 4 comatose patients resuscitated from cardiac arrest
      treated with mild hypothermia. On hospital admission, all patients had a Glasgow
      Coma Score between 3 and 6 and a FOUR Score between 1 and 5. Mild hypothermia (32
      degrees C - 33 degrees C) was implemented for 24 to 40 hours. Examination by
      board-certified neurologists before and during hypothermia or the rewarming phase
      suggested a grave prognosis. All 4 patients had sudden and dramatic neurologic
      recovery 9 to 24 hours after rewarming to normothermia and were ultimately
      discharged with no or minimal neurocognitive sequelae. CONCLUSION: This case
      series suggests that neurologic assessment-based prognosis of patients after
      cardiac arrest undergoing therapeutic mild hypothermia should be considered
      unreliable for at least the first 72 hours. Use of additional assessments such as
      brain injury markers or evoked potentials, in addition to clinical examination,
      should be strongly considered to help determine an estimated prognosis.
      Functional reversibility after a global insult could be an intrinsic potential of
      the brain, similar to myocardial stunning, and deserves investigation.

PMID- 18090716
TI  - Isolated hand palsy due to cortical infarction: localization of the motor hand
      area.
AB  - OBJECTIVE: To evaluate the cortical presentation of the hand area according to
      MRI images of the infarcted area in patients who have predominantly hand
      weakness. BACKGROUND: "Pseudoperipheral palsy" is an old term employed to
      describe a rare clinical picture consisting of predominant weakness of the hand
      in association with cerebral infarction. Because the organization of the cortical
      efferent area of the hand has not been fully defined, this phenomenon merits
      attention. Recent advances in functional imaging have stimulated renewed interest
      in the cortical mapping of various body parts, particularly that of the hand.
      METHODS: The patients who had isolated hand palsy due to cerebral infarction
      underwent clinical examination and cerebral MRI investigation to locate the exact
      lesion site. RESULTS: Eight patients (6 men, 2 women) aged 55 to 80 years (mean
      69 years) were included in this study. All had at least one risk factor for
      cerebrovascular disease. All our 8 patients presented with hand palsy and lesions
      were detected in the contralateral precentral gyrus in all cases. The lesions
      were located in the middle to lower portion of the anterior wall of the central
      sulcus just posterior to the intersection of the superior frontal and precentral
      sulci. CONCLUSION: Our findings indicate that the hand area in the cerebral motor
      cortex is located in the middle to lower portion of the anterior wall of the
      central sulcus, that is, in Brodmann area 4. We present our 8 patients showing
      isolated hand palsy due to a discrete cortical infarction on MRI to expand the
      knowledge about cortical localization of the hand area.

PMID- 18090717
TI  - 10 questions about the clinical determination of brain death.

PMID- 18090718
TI  - Sniffing out Parkinson disease: can olfactory testing differentiate parkinsonian
      disorders?
AB  - BACKGROUND: : Akinetic-rigid syndromes are a heterogeneous group of diseases with
      overlapping clinical manifestations. A recent American Academy of Neurology
      practice parameter indicated that olfactory testing was "probably useful" for
      differentiating idiopathic Parkinson disease (IPD) from other diseases with
      features of parkinsonism. OBJECTIVE: : To determine the diagnostic accuracy of
      olfactory testing for differentiating IPD from other parkinsonian disorders.
      METHODS: : The objective was addressed using a structured, evidence-based,
      critically appraised topic format. This format includes development of a clinical
      scenario, focused and answerable clinical question, search strategy, evidence
      appraisal, reporting and interpretation of results, commentary, and bottom line
      conclusions. Participants included neurology consultants and residents, clinical
      epidemiologists, a medical librarian, and neurologists with expertise in movement
      disorders. RESULTS: : Two studies evaluated the diagnostic accuracy of olfactory
      testing within a broad spectrum of parkinsonian syndromes. Each study examined
      different test methods [University of Pennsylvania Smell Identification Test;
      "Sniffin' Sticks"] and both were compromised by several potential biases in
      sampling and outcome evaluation. The University of Pennsylvania Smell
      Identification Test is moderately sensitive (77%; likelihood ratio 0.27) and
      specific (85%; likelihood ratio 4.9) for differentiation of IPD from non-IPD
      syndromes, but less specific (62%; likelihood ratio 2.0) for distinguishing IPD
      from multiple system atrophy. CONCLUSION: : The diagnostic accuracy of olfactory
      testing for differentiating IPD from other disorders is insufficient to justify
      its routine clinical use but available evidence is derived from small samples and
      studies of questionable validity. Recommendations for future research of
      olfactory testing for diagnosis and disease predication are discussed.

PMID- 18090719
TI  - Medications for Parkinson's disease.

PMID- 18090720
TI  - HTLV-I and neurological disease: from tropical spastic paraparesis to HTLV-I
      associated myelopathy: what next?

PMID- 18090725
TI  - Evaluation and treatment of zygomatic fractures.
AB  - Orbitozygomatic fractures are some of the most common facial fractures evaluated
      and treated by plastic surgeons. A considerable debate remains surrounding the
      manner of evaluation and appropriate treatment modalities. On the one hand, some
      would suggest that few fractures need formal open reduction and internal
      fixation, whereas others would argue that the pull of the strong masseter muscle
      ultimately leads to inferior and lateral rotation of the zygoma, which justifies
      open reduction and internal fixation of most fractures excepting those fractures
      that are nondisplaced at all points of articulation. The authors hope to shed
      some light on these issues by conveying their perspective on these fractures that
      has developed over several decades while servicing a single, major Level I trauma
      center. In general, the authors feel that through a detailed evaluation including
      an accurate physical examination of the face and orbit combined with detailed
      computed tomographic scanning of the craniofacial skeleton and soft tissues, an
      appropriate treatment plan can be generated. The common goal among all treatment
      plans should be the exact three-dimensional restoration of the disturbed anatomy,
      that is, anatomical reduction and the need for accurate restoration of orbital
      anatomy and volume when necessary.

PMID- 18090726
TI  - Nasoethmoid orbital fractures: diagnosis and treatment.
AB  - Blunt trauma to the midface frequently results in fractures of the nasoethmoid
      orbital skeleton. These complex injuries are often misdiagnosed or inadequately
      treated and are perhaps the most difficult of all facial fractures to treat. The
      purpose of this article is to describe the author's technique for the diagnosis
      and treatment of these complex fractures. Presented is an organized approach to
      the diagnosis and surgical management of nasoethmoid orbital fractures that has
      evolved in the author's treatment of over 450 nasoethmoid fractures. Early
      diagnosis is confirmed by computed tomographic scan using the simple
      classification system described. Fractures that demonstrate displacement or
      movement on examination require open reduction and stabilization. Identifying the
      extent and type of fracture pattern and associated injuries determines the
      exposure and method of fixation needed. Wide exposure with meticulous reduction
      is necessary, with stabilization of the medial orbital rim fragment using a
      transnasal wire technique. Plate-and-screw fixation of the superior and inferior
      rim is performed with bone graft reconstruction of the nose as needed. Attention
      to redraping of soft tissue in the naso-orbital valley with the use of nasal
      compression bolsters is a crucial step in the repair. Multiple clinical cases are
      used to illustrate the different fracture patterns, soft-tissue injuries, and
      surgical technique recommended. This organized approach has proven effective in
      restoring preinjury appearance. Early diagnosis combined with the aggressive
      surgical techniques described will optimize results and minimize the late
      posttraumatic deformity.

PMID- 18090727
TI  - Management of frontal sinus fractures.
AB  - Frontal sinus fractures are relatively uncommon maxillofacial injuries, making up
      only 5 to 12 percent of all facial fractures. Associated intracranial,
      ophthalmologic, and other maxillofacial injuries are very common because of the
      force of injury required to fracture the frontal bone. High-resolution computed
      tomography of the frontal region in multiple planes is essential for predicting
      the degree of frontal injury, associated injuries, and the type of procedure
      indicated. Exploration of the frontal sinus with reduction alone is reserved for
      a small minority of very simple fractures. Most frontal sinus fractures will
      require the obliteration of the sinus. This is achieved in the majority of
      instances with preservation of the posterior wall. Those with more extensive
      injuries and the presence of a cerebrospinal fluid leak will require frontal
      sinus cranialization after repair of the dural injuries. In rare instances,
      primary bone grafts will be required. In both cranialization and obliteration
      procedures, the nasofrontal ducts must be managed appropriately to avoid
      complications. Newer techniques involving endoscopic image-guided surgery may
      offer an alternative for a small subset of patients with frontal sinus injury.

PMID- 18090728
TI  - The eye examination in facial trauma for the plastic surgeon.
AB  - Fifteen to 20 percent of patients with major facial trauma suffer vision
      threatening injuries. Not only does the early identification and management of
      such ophthalmic insults frequently carry a better visual prognosis, but
      manipulations during facial fracture repair may exacerbate unrecognized eye
      trauma. In addition, ophthalmic problems not documented before facial
      reconstruction may be interpreted as direct complications of surgery. Thus, all
      physicians who treat patients with trauma above the mandible should appreciate
      the fundamentals of ophthalmic evaluation and emergency management. This article
      strives to provide a simplified, practical guide, but it should not be viewed as
      a substitute for consultation by a qualified eye care provider when an ocular
      injury is strongly suspected.

PMID- 18090729
TI  - Comprehensive management of orbital fractures.
AB  - Orbital fractures are some of the more challenging injuries faced by the plastic
      surgeon. As such a prominent facial feature, even the most minor asymmetries
      following trauma can be distressing to the patient. In treating these patients,
      there are certain crucial aspects of both diagnosis and management that are
      critical to obtaining an optimal result. These include a careful preparative eye
      examination focusing on extraocular motility and any evidence of optic nerve
      compression. Candidates for surgery must be carefully selected based on firm
      indications such as a large orbital floor defect (>1 cm2), early enophthalmos,
      significant hypoglobus, or persistent diplopia in the primary field of gaze.
      Reconstruction should focus on anatomical restitution of the floor, taking great
      care to place the implant along the correct superior inclination of the orbit.

PMID- 18090730
TI  - Nasal trauma and the deviated nose.
AB  - As the most prominent facial feature, the nose carries an increased risk of
      traumatic injury. Nasal fracture is the most common bone injury of the adult face
      and frequently results from motor vehicle accidents, sports-related injuries, and
      altercations. Although often initially considered minor, nasal fracture may
      eventually result in significant cosmetic or functional defects. Optimal
      management of nasal trauma in the acute setting is critical in minimizing
      secondary nasal deformities. In recent years, numerous guidelines have been
      described to refine and optimize acute nasal trauma management. However,
      restoration of pretraumatic form and function remains a challenge. Commonly the
      product of a poorly addressed underlying structural injury, posttraumatic nasal
      deformity requiring subsequent rhinoplasty or septorhinoplasty remains in as many
      as 50 percent of cases. In this article, the authors review the anatomic,
      diagnostic, and management considerations as well as discuss their own experience
      in approaching nasal trauma and the deviated nose.

PMID- 18090731
TI  - Fractures of the mandible: a technical perspective.
AB  - The purpose of this article is to describe the treatment of mandibular fractures
      using principles of functionally stable or rigid internal fixation techniques.
      The fixation requirements for various fractures of the mandible, excluding those
      of the condylar process (which are discussed in another article), are described
      using mandibular biomechanics as a basis for the recommendations.

PMID- 18090732
TI  - Closed reduction, open reduction, and endoscopic assistance: current thoughts on
      the management of mandibular condyle fractures.
AB  - The management of fractures of the mandibular condyle continues to be
      controversial. This is in part attributable to a misinterpretation of the
      literature from decades prior, a lack of uniformity of classification of the
      various anatomical components of the mandibular condyle, and a perceived
      potential to cause harm through the open approach based in part on the surgeon's
      lack of a critical examination of the literature. This review explores the key
      historical articles that deal with the management of mandibular condyle
      fractures, and those modern-day contributions that represent the state of the
      art. The authors' intention was to provide the reader with an objective summary
      of the management of this form of injury, to place its management into a modern
      day perspective, and perhaps to minimize the perception of controversy.

PMID- 18090733
TI  - Microsurgical reconstruction of posttraumatic high-energy maxillary defects:
      establishing the effectiveness of early reconstruction.
AB  - BACKGROUND: Posttraumatic, high-energy defects of the midface can be challenging
      to reconstruct because they involve extensive composite tissue loss and result in
      significant permanent functional and cosmetic deformity. These injuries require
      replacement of the bony framework, external soft tissue, and intraoral mucosa.
      Local skin flaps and nonvascularized bone grafts have been used for
      reconstruction, but bony resorption and the associated soft-tissue collapse limit
      long-term viability. The authors present a classification of maxillary defects
      following high-energy trauma and a treatment algorithm using vascularized bone
      flaps. METHODS: Fourteen patients with significant maxillary loss from high
      energy trauma underwent reconstruction with composite vascularized bone flaps.
      Eight patients had fibula flaps and six had iliac crest flaps. There were five
      women and nine men, with a mean age of 36.3 years (range, 21 to 48 years) and a
      mean follow-up of 18 months (range, 5 to 54 months). RESULTS: Thirteen of the 14
      flaps survived. Nine patients had additional procedures. Nine patients had
      oronasal fistulas and eight were dependent on gastrostomy tubes preoperatively.
      All patients were able to feed orally without nasal regurgitation
      postoperatively. All patients achieved stable restoration of the midfacial
      architecture. CONCLUSIONS: The classification scheme presented centers on the
      missing maxillary subunits. The reconstructive algorithm is based on the type of
      defect, tissue requirement, and donor tissues necessary to restore facial
      projection and prosthodontic rehabilitation. Iliac crest and fibula bone free
      flaps are ideal for restoring a variety of traumatic maxillary defects. The
      authors advocate early reconstructive intervention using vascularized bone flaps
      to achieve superior functional and cosmetic outcomes.

PMID- 18090734
TI  - Periorbital necrotizing fasciitis.

PMID- 18090735
TI  - Hemifacial microsomia: clinical features and pictographic representations of the
      OMENS classification system.
AB  - LEARNING OBJECTIVES: After reviewing this article, the participant should be able
      to: 1. Describe the fundamental malformations defining hemifacial microsomia. 2.
      Distinguish hemifacial microsomia from other congenital craniofacial anomalies
      sharing similar features. 3. Understand the variety of systems developed to
      clinically classify the features of this disorder. 4. Describe the format of the
      OMENS clinical classification system and appreciate its possible advantages and
      limitations. BACKGROUND: The clinical manifestations of hemifacial microsomia
      comprise a spectrum that is both broad and complex. The fundamental features
      include unilateral hypoplasia of the craniofacial skeleton and its overlying soft
      tissue. Numerous schemes have been developed to classify this spectrum. One of
      the most recent classification systems, the OMENS system, scores five clinical
      manifestations of hemifacial microsomia according to dysmorphic severity on a
      scale from 0 to 3: orbital asymmetry, mandibular hypoplasia, ear deformity, nerve
      dysfunction, and soft-tissue deficiency. METHODS: The authors describe the
      diverse features of hemifacial microsomia and the numerous attempts at its
      clinical classification, with particular emphasis on the OMENS system. RESULTS:
      With the possible exception of the OMENS scheme, the various systems developed to
      classify the clinical features of hemifacial microsomia fail to possess the
      flexibility and versatility needed to categorize all potential phenotypes of this
      complex disorder. CONCLUSIONS: The OMENS system represents the most
      comprehensive, versatile, objective, and easily adaptable attempt at clinical
      classification of hemifacial microsomia to date. The authors propose a concise
      clinical evaluation form using a modified version of the system to promote the
      use of the OMENS system, to aid in the evaluation of hemifacial microsomia
      patients, and to assist in data sharing among academic institutions.

PMID- 18090736
TI  - Y-scar vertical mammaplasty.
AB  - BACKGROUND: Vertical mammaplasty is an effective alternative to inverted-T
      methods. Among other benefits, it results in a significantly reduced scar
      pattern. There exists a subset of patients with mild macromastia and minimal
      ptosis who are candidates for a scar pattern that is further reduced. These
      patients are usually young and have limited enlargement of the areolae. The upper
      half of the circumareolar incision can be deleted in these patients to result in
      a Y-shaped scar pattern. This technique is also applicable to some patients
      seeking mastopexy with augmentation. METHODS: Ten patients meeting the criteria
      described were treated with Y-scar vertical mammaplasty and were reviewed
      retrospectively. RESULTS: Eight patients had breast reduction or mastopexy and
      two patients had mastopexy with augmentation. The average amount of tissue
      removed from each breast in the reduction group was 198 g (range, 76 to 382 g).
      The average follow-up period was 8.4 months. Problems encountered were minor and
      included inferior areolar fullness in three patients and an inverted nipple in
      one patient. One patient developed a unilateral lower pole deformity several
      months after surgery that required corrective surgery. All patients were pleased
      with their final surgical outcome. CONCLUSIONS: The Y-shaped scar incision design
      is useful in appropriate candidates to further reduce the scar burden associated
      with vertical mammaplasty. Retaining the normal transition from pigmented areolar
      skin to adjacent lighter skin in the upper half of the areola significantly
      reduces the perception of the overall scar pattern.

PMID- 18090737
TI  - Practical guidelines for repair of partial mastectomy defects using the breast
      reduction technique in patients undergoing breast conservation therapy.
AB  - BACKGROUND: The authors previously compared the local tissue rearrangement,
      breast reduction, and latissimus dorsi flap reconstruction techniques for
      repairing partial mastectomy defects and showed the benefits of breast reduction.
      METHODS: In this study, the authors focused solely on factors influencing outcome
      in 41 patients who underwent repair of a partial mastectomy defect using breast
      reduction. RESULTS: Tumor location had a significant effect on the design of the
      parenchymal pedicle (p = 0.05). Most repairs were performed with an inferior
      pedicle. Fifty percent of the lower outer and central quadrant tumors required an
      amputative design with a free nipple graft. The complication rates for immediate
      and delayed repair were 24 and 50 percent, respectively. The superior pedicle was
      associated with the highest complication rates. Tumors in the upper outer
      quadrant of the breast were associated with the highest complication rate (35
      percent). Ninety percent of patients with planned repairs had a viable nipple
      areola complex (p = 0.05) and did not require a free nipple graft. More favorable
      cosmetic outcomes were achieved using an inferior pedicle; less favorable
      cosmetic outcomes were achieved for tumors in the upper inner quadrant of the
      breast. Larger defects did not result in less favorable cosmetic outcomes than
      smaller defects. Only 7 percent of patients had a positive tumor margin. Five
      percent of patients developed local breast cancer recurrence after a mean follow
      up of 36 months. CONCLUSION: The authors provide practical guidelines for
      repairing a partial mastectomy defect using breast reduction that should minimize
      the occurrence of complications and optimize the cosmetic outcome.

PMID- 18090738
TI  - Internal mammary perforator recipient vessels for breast reconstruction using
      free TRAM, DIEP, and SIEA flaps.
AB  - BACKGROUND: Use of internal mammary perforator recipient vessels may decrease
      recipient-site morbidity in free flap breast reconstruction. However, it is not
      known whether they are as reliable as the internal mammary vessels or whether
      their use would result in increased recipient-site complications. METHODS: A
      retrospective study of all 686 lower abdominal free flap breast reconstructions
      performed during a 4-year period at the authors' institution identified 38 cases
      in which internal mammary perforator vessels were used. A subset of 114 of the
      686 cases was studied in which patients were treated by a single surgeon,
      internal mammary perforator vessel use was attempted, and vessel measurements
      were taken intraoperatively. RESULTS: Internal mammary perforator recipient
      vessels were used in 27 percent of cases attempted, 94 percent of which were
      located at the second or third intercostal space. Internal mammary perforator
      arteries were significantly smaller in diameter (1.9 mm) than internal mammary
      arteries (2.6 mm) (p < 0.0001). Despite this, the incidences of flap loss, fat
      necrosis, and mastectomy skin flap necrosis were not significantly different
      between the internal mammary and internal mammary perforator vessel groups. The
      internal mammary and internal mammary perforator veins were similar in diameter.
      CONCLUSIONS: To the authors' knowledge, this is the largest published series of
      internal mammary perforator vessels used as free flap recipient vessels. In
      selected cases, internal mammary perforator vessels can be used without
      increasing the risk of flap loss, fat necrosis, or mastectomy skin flap necrosis,
      and are equally reliable and require less invasive surgical dissection than
      internal mammary vessels. The use of internal mammary perforator vessels may
      safely minimize recipient-site morbidity.

PMID- 18090739
TI  - The effect of recombinant human erythropoietin on ischemia-reperfusion injury: an
      experimental study in a rat TRAM flap model.
AB  - BACKGROUND: Erythropoietin is traditionally known to regulate erythropoiesis, but
      recently its protective effect against ischemia-reperfusion injury has been
      studied in cardiovascular and neuronal systems. This study investigated the
      effect of recombinant human erythropoietin on ischemia-reperfusion injury in a
      rat transverse rectus abdominis musculocutaneous (TRAM) flap model. METHODS:
      Twenty-four Sprague-Dawley rats were divided into a control group (n = 12) and a
      group treated with erythropoietin (n = 12). A superiorly based TRAM flap was
      elevated and ischemic insult was given for 4 hours. Thirty minutes before
      reperfusion, single-dose recombinant human erythropoietin (5000 IU/kg) was
      injected through the intraperitoneal route in the treatment group. At 24 hours
      postoperatively, systemic neutrophil count, tissue myeloperoxidase activity,
      amount of malondialdehyde, nitric oxide content, tissue water content, and
      histologic finding of inflammation were evaluated. At day 10 postoperatively,
      flap survival rate, angiogenesis, and change in hematocrit level were evaluated.
      RESULTS: The myeloperoxidase activity and tissue water content were significantly
      lower (p < 0.01 and p < 0.005, respectively), and the tissue nitric oxide level
      was significantly higher (p < 0.005) in the treatment group 24 hours after
      reperfusion. Perivascular neutrophil infiltration and intravascular adhesion were
      marked in the control group. Mean flap survival after 10 days was 69 percent in
      the treatment group and 47 percent in the control group, demonstrating a
      significant difference (p < 0.005). Neovascularization in the treatment group was
      also greater than that in the control group. No significant hematocrit rise was
      noted 10 days after erythropoietin administration. CONCLUSION: Recombinant human
      erythropoietin improved flap survival in ischemia-reperfusion-injured rat TRAM
      flaps by the possible mechanism of suppressed inflammation, decreased
      infiltration of neutrophils, increased nitric oxide, and enhanced angiogenesis.

PMID- 18090740
TI  - Molecular and cellular characterization of mouse calvarial osteoblasts derived
      from neural crest and paraxial mesoderm.
AB  - BACKGROUND: Cranial skeletogenic mesenchyme is derived from two distinct
      embryonic sources: mesoderm and cranial neural crest. Previous studies have
      focused on molecular and cellular differences of juvenile and adult osteoblasts.
      METHODS: To further understand the features of mouse-derived juvenile
      osteoblasts, the authors separated calvarial osteoblasts by their developmental
      origins: frontal bone-derived osteoblasts from cranial neural crest, and parietal
      bone-derived osteoblasts from paraxial mesoderm. Cells were harvested from a
      total of 120 mice. RESULTS: Interestingly, the authors observed distinct
      morphologies and proliferation potential of the two populations of osteoblasts.
      Osteogenic genes such as alkaline phosphatase, osteopontin, collagen I, and
      Wnt5a, which was recently identified as playing a role in skeletogenesis, were
      abundantly expressed in parietal bone-derived osteoblasts versus frontal bone
      derived osteoblasts. In addition, fibroblast growth factor (FGF) receptor 2, and
      FGF-18 were more highly expressed in the parietal bone-derived osteoblasts,
      suggesting a more differentiated phenotype. In contrast, FGF-2, and adhesion
      molecules osteoblast cadherins and bone morphogenetic protein receptor IB, the
      bone tissue-specific type receptor were overexpressed in frontal bone-derived
      osteoblasts compared with parietal bone-derived osteoblasts. CONCLUSIONS: The
      authors observed that although neural crest-derived osteoblasts represented a
      population of less differentiated, faster growing cells, they formed bone nodules
      more rapidly than parietal bone-derived osteoblasts. This in vitro study suggests
      that embryonic tissue derivations influence postnatal in vitro calvarial
      osteoblast cell biology.

PMID- 18090741
TI  - Self-inducing shape memory geometric cues embedded within smart hydroxyapatite
      based biomimetic matrices.
AB  - BACKGROUND: The authors investigated in nonhuman primates (Papio ursinus) whether
      it is possible to engineer biomimetic matrices that induce the differentiation of
      osteoblastic cells expressing selected osteogenic mRNA species of the
      transforming growth factor (TGF)-beta superfamily. METHODS: Four types of
      sintered hydroxyapatite and biphasic hydroxyapatite/tricalcium phosphate
      bioceramics were evaluated as osteoinductive self-inducing biomimetic matrices.
      Matrices were fabricated with a series of repetitive concavities that initiate
      the induction of bone formation as a secondary response. Single-phase
      hydroxyapatite, biphasic hydroxyapatite/tricalcium phosphate, and carbon
      impregnated single-phase hydroxyapatite, the latter with fine and coarse
      porosities, were implanted heterotopically in the rectus abdominis. Specimens for
      orthotopic calvarial implantation were a total of 16 macroporous disks 25 mm in
      diameter of single-phase hydroxyapatite and biphasic hydroxyapatite/tricalcium
      phosphate. RESULTS: Heterotopic specimens 90 and 180 days after implantation
      showed the induction of bone within concavities of the biomimetic matrices.
      Northern blot analyses of heterotopic specimens showed that carbon-impregnated
      single-phase hydroxyapatite specimens induced high expression of osteogenic
      protein-1 mRNA, correlating with the induction of bone formation. Collagen type
      IV mRNA was highly expressed, particularly on day 90, by all the implanted
      matrices. Orthotopic specimens showed substantial bone formation across the
      implanted constructs. CONCLUSIONS: Self-induced bone has been achieved via the
      deployment of osteogenic molecular signals expressed by differentiating
      osteoblastic-like cells, later secreted and embedded into the smart concavities
      of the biomimetic matrices. The described biomimetic matrices induce de novo bone
      formation even in the absence of exogenously applied osteogenic proteins of the
      TGF-beta superfamily.

PMID- 18090742
TI  - Proteasome inhibitor attenuates skeletal muscle reperfusion injury by blocking
      the pathway of nuclear factor-kappaB activation.
AB  - BACKGROUND: Nuclear factor-kappaB is a key transcriptional factor in the
      regulation of inflammatory factors that are involved in tissue reperfusion
      injury, but conflicting data have been presented in the literature. The
      proteasome regulates proteins that control cell-cycle progression and apoptosis,
      and inhibition of the proteasome has been shown to reduce nuclear factor-kappaB
      activation and reperfusion injury. Although bortezomib is a potent proteasome
      inhibitor, its role in skeletal muscle reperfusion injury has not been
      documented, and its effects on the regulation of inflammatory factors in
      reperfused tissue are unclear. In this study, the authors investigated the role
      of nuclear factor-kappaB in skeletal muscle reperfusion injury and the effect of
      bortezomib (a proteasome inhibitor) on reperfusion injury. METHODS: Pedicled
      cremaster muscle flaps from bortezomib-treated and phosphate-buffered saline
      treated control mice were subjected to 4.5 hours of ischemia and 90 minutes of
      reperfusion. RESULTS: During reperfusion, arterial diameters and blood flow
      recovered earlier and more completely in bortezomib-treated muscle than in
      controls. Compared with controls, Western blot analysis demonstrated a
      significant reduction in degradation of nuclear factor-kappaB inhibitory protein
      and expression of inducible nitric oxide synthase protein in bortezomib-treated
      muscle at the end of reperfusion. Immunohistochemistry showed decreased nuclear
      factor-kappaB p65-binding activity and down-regulated protein expression of
      intercellular adhesion molecule-1 and nitrotyrosine, accompanied by less muscle
      edema and inflammation as proven by histologic examination. CONCLUSIONS:
      Bortezomib effectively blocks nuclear factor-kappaB activation in attenuating
      muscle reperfusion injury through inhibiting nuclear factor-kappaB inhibitory
      protein degradation. Therefore, inhibition of proteasome activity may provide a
      novel therapeutic strategy for the treatment of skeletal muscle reperfusion
      injury.

PMID- 18090743
TI  - Dimethyl sulfoxide as a block to the deleterious effect of nicotine in a random
      skin flap in the rat.
AB  - BACKGROUND: In plastic surgery, a causal relationship between heavy smoking and
      flap necrosis has been shown. The deleterious effect of nicotine in random skin
      flaps in rats has also been proven, being related to vasoconstriction and
      possibly reactive oxygen species. This study aimed to verify the capacity of
      dimethyl sulfoxide, an antioxidant, to block the deleterious effect of nicotine
      in a random skin flap. METHODS: Fourteen adult male Wistar-EPM rats were
      distributed at random into two groups of seven animals. The nicotine group
      received this drug subcutaneously (1.2 mg/kg/day), for 1 week before flap
      elevation. The nicotine plus dimethyl sulfoxide group followed the same routine.
      Five minutes before the surgical procedure, rats in the nicotine group received
      distilled water orally and rats in the nicotine plus dimethyl sulfoxide group
      received dimethyl sulfoxide orally (2 ml/kg). Blood and skin tissue samples were
      collected to allow determination of malondialdehyde levels. RESULTS: The nicotine
      group had a mean value of 40.2 percent and the nicotine plus dimethyl sulfoxide
      group had a mean value of 20.6 percent necrosis (p = 0.009). Malondialdehyde
      levels in both serum and skin samples were lower in the animals that received
      dimethyl sulfoxide. CONCLUSION: The deleterious effect of nicotine was
      effectively blocked by dimethyl sulfoxide.

PMID- 18090744
TI  - The effects of botulinum toxin type A on muscle blood perfusion and metabolism.
AB  - BACKGROUND: Botulinum toxin type A is approved by the U.S. Food and Drug
      Administration for the treatment of facial rhytides. However, the complete
      spectrum of action of botulinum toxin A has not yet been completely defined.
      Little is known about the metabolism of muscle after botulinum toxin A injection.
      This information may give insight into the additional effects botulinum toxin A
      may have on muscle. The authors assessed the influence of botulinum toxin A on
      the metabolism of muscle using dynamic investigative techniques. METHODS: Twenty
      New Zealand White rabbits were divided into control, paralysis, and sham groups.
      Masseter muscle paralysis was achieved with botulinum toxin A. Dynamic computed
      tomographic and positron emission tomographic scans were obtained. Masseter
      muscle blood flow, blood volume, permeability surface, and mean transit time and
      glucose uptake were measured. RESULTS: Eighteen animals completed the study.
      Masseter blood perfusion showed consistent results across all parameters. Blood
      flow, blood volume, and permeability surface were significantly increased at
      weeks 4 and 8 on the paralyzed side. Mean transit time at week 4 was decreased on
      the paralyzed side. Positron emission tomographic scans showed that injected
      muscles in the botulinum toxin A group tended to have increased glucose uptake
      compared with untreated muscles. CONCLUSIONS: Botulinum toxin A injection
      increases muscle blood perfusion parameters and glucose uptake for a transient
      period. This increase is similar in duration to the known interval of botulinum
      toxin A-induced paralysis. These changes have been identified in a dynamic
      fashion and may represent changes in calcitonin gene-related peptide release.

PMID- 18090745
TI  - Systematic reviews: a primer for plastic surgery research.
AB  - Clinicians rely on review articles to keep current with the rapid accumulation of
      medical and surgical literature. Traditional expert reviews, however, often
      suffer from inherent personal biases and may not reflect a true synthesis of the
      existing literature on a particular subject. Systematic reviews are structured,
      scientific articles that address the shortcomings of traditional reviews by
      adhering to strict, reproducible methods and recommended guidelines. The methods
      are designed to eliminate possible sources of bias, ensure as complete a review
      of the existing literature as possible, and present the results in a way that is
      useful for its intended audience. Systematic reviews may at times include a
      quantitative synthesis of the available data in the form of a meta-analysis. Meta
      analysis is a statistical tool for combining the numerical results of separate
      studies to obtain a summary outcome with increased precision due to the larger,
      combined number of patients. Meta-analyses may be particularly helpful when
      individual study results are conflicting and the existing literature is
      inconclusive. The validity of meta-analysis, however, is highly dependent on the
      quality of data available in the literature. In its strictest form, meta-analysis
      is used to combine data from only randomized controlled clinical trials. Because
      randomized controlled clinical trials are infrequently performed in plastic
      surgery research, this article will focus on systematic reviews to provide the
      readers with a useful guide in performing this field of study.

PMID- 18090746
TI  - Surgical algorithm for management of HIV lipodystrophy.
AB  - BACKGROUND: The accepted standard for treatment of human immunodeficiency virus
      disease, highly active antiviral therapy, may cause significant side effects,
      such as facial lipoatrophy and lipodystrophy. Facial wasting or a buffalo hump
      deformity may be pathognomonic for treated human immunodeficiency virus disease.
      In addition to facial wasting, cystic parotid degeneration may further distort
      the face. The authors outline the defects as a series of triangles defined by
      anatomical boundaries. METHODS: In a group of 27 patients, 17 were treated for
      buffalo hump (three isolated and 14 with associated facial wasting). Another 10
      patients were treated for isolated facial wasting. RESULTS: The 14 patients who
      underwent liposuction of the buffalo hump with subsequent injection of the
      aspirate into the face had approximately 40 to 50 percent of the grafts survive.
      Recurrent or severely fibrous humps were treated with ultrasound-assisted
      liposuction. In six patients, autografts to the lypoatrophic face were utilized.
      Two patients undergoing gynecomastia reduction had successful grafting with the
      resected breast. Three patients with cystic degeneration of the parotid underwent
      superficial parotidectomy with rotation or grafting of the parotid into the
      defect, for a total of six individual procedures. CONCLUSION: The authors present
      an algorithm for treatment of buffalo hump and facial wasting deformities
      associated with human immunodeficiency virus lipodystrophy syndrome, with an
      emphasis on long-term results with autogenous tissue.

PMID- 18090747
TI  - Myectomy and botulinum toxin for paralysis of the marginal mandibular branch of
      the facial nerve: a series of 76 cases.
AB  - BACKGROUND: Paralysis of the marginal mandibular branch of the facial nerve is
      frequently seen in patients with oromandibular reconstructions or facial palsy.
      However, deformities caused by overpulling of the depressor muscles of the
      contralateral lower lip without being antagonized by the diseased counterpart is
      often quite conspicuous. Depressor myectomy of the contralateral lower lip
      therefore provides a method for correcting the dynamic deformity. METHODS:
      Seventy-six patients with paralysis of the marginal mandibular branch of the
      facial nerve were treated with either surgical depressor myectomy of the lower
      lip (25 patients), depressor myectomy with subsequent botulinum toxin injection
      (eight patients), or only chemical depressor myectomy with botulinum toxin
      injections (43 patients). RESULTS: Good to fair results were always achieved,
      with near balance of the lower lip during mouth opening and in facial
      expressions. Surgical myectomy may still result in recurrence in eight patients
      (24 percent), which will necessitate further treatment with botulinum toxin
      injections. CONCLUSIONS: Using myectomy for paralysis of the marginal mandibular
      branch of the facial nerve can be an effective treatment for this significant
      deformity. Chemical myectomy with botulinum toxin injection is a safe and
      convenient mode of treatment; however, the disadvantage is that it needs repeated
      injections and costs more.

PMID- 18090748
TI  - Maxillary artery: anatomical landmarks and relationship with the mandibular
      subcondyle.
AB  - BACKGROUND: The maxillary artery can be injured during procedures in the
      subcondylar portion of the mandible. Thorough knowledge of this region is
      mandatory to avoid accidental puncture of the maxillary artery, which can lead to
      profuse bleeding that is hard to control. METHODS: In 16 halves of eight embalmed
      cadaver heads, the maxillary artery was dissected from the branching point to the
      entrance point to the maxillary sinus. Its anatomical relationships with certain
      landmarks were recorded numerically. RESULTS: The mean distance of the branching
      point of the maxillary artery to the tragal pointer was 16.2 mm (range, 14.97 to
      16.80 mm) in the horizontal plane and 21.4 mm (range, 19.14 to 23.53 mm) in the
      vertical plane. The mean vertical distance of the branching point to the
      Frankfort horizontal plane was 25.7 mm (range, 24.86 to 27.47 mm). The mean
      distance of the branching point of the maxillary artery to the tip of the condyle
      was 22.4 mm (range, 21.66 to 23.99 mm). The mean distance of the artery to the
      medial border of the subcondylar portion of the mandible was 6.8 mm (range, 4.06
      to 8.47 mm). The mean distance between the deepest point of the sigmoid notch and
      the junction of the maxillary artery and sigmoid notch was 5.1 mm (range, 4.97 to
      5.95 mm). The mean distance of the maxillary artery-sigmoid notch junction to the
      tragal pointer was 22.9 mm (range, 20.95 to 25.05 mm). CONCLUSIONS: The maxillary
      artery can be injured during surgical procedures performed in the
      temporomandibular region. Its relationship with the subcondylar portion of the
      mandible varies.

PMID- 18090749
TI  - The role of free-tissue transfer for head and neck burn reconstruction.
AB  - BACKGROUND: The reconstruction of head and neck burns is challenging,
      traditionally involving skin grafting and local flaps. Free flaps have improved
      in versatility and variability in recent years, and are now among the techniques
      used for burn reconstruction. METHODS: Thirty-six free flaps for 32 patients with
      cervicofacial burns were reviewed retrospectively over a 17-year period (1989 to
      2005) to determine indications, methods, and outcomes. RESULTS: The mean patient
      age was 31 years. Thirteen flaps were transferred to the neck and 23 to the face.
      The main indication was contractures or hypertrophic scarring followed by exposed
      bone or cartilage. The majority of flaps were transferred for secondary
      reconstruction. The free flaps most frequently used were the anterolateral thigh
      (31 percent), scapular/parascapular (31 percent), and radial forearm (17
      percent). Fourteen were prefabricated, one was prelaminated, and 15 were tissue
      expanded. A total of 34 flaps (94 percent) were successful. There were no deaths,
      two donor-site complications, a 17 percent tip necrosis rate, and a 6 percent
      flap infection rate. The median hospital stay was 6 days after free flap
      transfer. Patients were followed for at least 1 year, and 64 percent of flaps
      needed further debulking or sculpting. CONCLUSIONS: Free tissue transfer is a
      valuable tool in head and neck burn reconstruction. It can be used safely and
      effectively with minimal morbidity in selected patients.

PMID- 18090750
TI  - Superficial temporal artery and vein as recipient vessels for facial and scalp
      microsurgical reconstruction.
AB  - BACKGROUND: Although free flap transfer is commonly performed to reconstruct
      defects of the upper two-thirds of the face and scalp, the superficial temporal
      artery and vein have historically not been considered adequate for microsurgical
      reconstruction and have rarely been described as recipient vessels. The purpose
      of this study was to determine the indications for and effectiveness of using the
      superficial temporal vessels for scalp and face reconstruction. METHODS:
      Retrospective chart review on all patients undergoing microsurgical
      reconstruction for defects of the upper two-thirds of the face between 1996 and
      2003 revealed 45 free tissue transfers in which the superficial temporal artery
      and vein were considered for use as recipient vessels. Flap success rates and
      postoperative course were evaluated. RESULTS: Forty-three patients underwent 45
      free flap transfers. The superficial temporal artery was used as the recipient
      artery in every case. In three cases, the superficial temporal vein was not
      suitable as the recipient vein and required use of a vein in the neck. The median
      length of follow-up was 4 years. Flap survival was 96 percent. Five patients
      required reoperation for vascular compromise. One of these patients ultimately
      had flap failure. In that patient, a subsequent attempt at microvascular flap
      reconstruction was successful using the same superficial temporal artery and vein
      as recipient vessels. CONCLUSIONS: Use of the superficial temporal artery and
      vein for scalp and face reconstruction is reliable and safe. The superficial
      temporal artery and vein should be considered as primary recipient vessels in
      microsurgical reconstruction of the upper two-thirds of the face and/or scalp.

PMID- 18090751
TI  - Single-stage muscle flap reconstruction of the postpneumonectomy empyema space:
      the Emory experience.
AB  - BACKGROUND: Postsurgical chronic empyema continues to present a complicated
      treatment scenario for thoracic and reconstructive surgeons. Muscle flaps are an
      important option in the management of complex thoracic wounds. This study was
      designed to report the Emory experience with muscle flaps for the management of
      complex postsurgical empyema. The authors also present their treatment algorithm
      for managing empyema thoracis. METHODS: The authors retrospectively reviewed the
      charts of 55 patients requiring different treatment modalities, including muscle
      flap transposition. Patients were divided into four groups according to the
      initial thoracic procedure: group A, no surgical resection; group B,
      postpneumonectomy; group C, postlobectomy; and group D, prophylactic
      postpneumonectomy or postlobectomy. The study included 42 men (76.4 percent) and
      13 women with a mean age of 62 years (range, 39 to 77 years). RESULTS: Fifty-one
      muscle flap procedures were performed in 42 patients (serratus anterior flaps, 16
      patients and 23 flaps; latissimus dorsi flaps, 16 patients and 18 flaps;
      pectoralis major muscle flaps, intercostal muscle flaps, and rectus abdominis
      flaps, three patients each: omental flap, one patient). The mean number of ribs
      resected before flap intervention, usually during the open window thoracostomy,
      was three. The average time from initial thoracic operation to flap intervention
      was 4 months. Average time from flap intervention to discharge was 12.5 days.
      Average hospital stay was 26.6 days. The 51 muscle flaps represented an average
      of 1.2 procedures per patient. CONCLUSION: Because of the excellent blood supply
      of extrathoracic muscle flaps and their ability to reach any place in the pleural
      cavity, they represent an ideal tissue with which to fill the contaminated
      pleural space.

PMID- 18090752
TI  - Development and validation of a novel scar evaluation scale.
AB  - BACKGROUND: The authors previously developed a six-item ordinal wound evaluation
      scale to measure the short-term cosmetic outcome of wounds 1 week after injury.
      Although it was never intended to measure long-term outcomes, it has been used to
      assess scars 3 to 12 months after injury. The authors developed and validated a
      scar evaluation scale specifically aimed at measuring the long-term appearance of
      scars. METHODS: Two plastic surgeons and one emergency physician, blinded to each
      other's assessments, viewed photographs of 50 scars resulting from lacerations or
      surgical incisions. Scars were assigned 0 or 1 point each for the presence or
      absence of the following: width greater than 2 mm, elevation or depression,
      discoloration, suture or staple marks, and overall poor appearance. A total
      cosmetic score was then calculated by adding the individual scores on each of the
      five categories ranging from 0 (worst) to 5 (best). Scars were also scored on a
      validated 100-mm visual analogue scale marked "worst scar" and "best scar" at the
      low and high ends, respectively. Pairwise interobserver agreement was calculated.
      RESULTS: Interobserver agreement for the total scores on the scar evaluation
      scale was 0.73, 0.75, and 0.85 (p < 0.001 for all). Interobserver correlations on
      the visual analogue scale were 0.83, 0.86, and 0.87 (p < 0.001 for all).
      Correlations between the total scar evaluation scale and visual analogue scale
      scores were 0.75, 0.86, and 0.92. Visual analogue scale scores were significantly
      higher as scar evaluation scale scores increased (analysis of variance, p <
      0.001). CONCLUSION: The authors describe a new long-term scar evaluation scale
      that is highly reliable and correlated with the cosmetic visual analogue scale,
      suggesting construct validity.

PMID- 18090753
TI  - Venous bypass drainage of the small saphenous vein in the neurovascular pedicle
      of the sural flap: anatomical study and clinical implications.
AB  - BACKGROUND: Little is known about the necessary dimensions of the neurovascular
      pedicle of the sural flap for inclusion of the concomitant bypass veins of the
      small saphenous vein to secure sufficient retrograde venous flow. Therefore, the
      authors evaluated the anatomical basis for venous outflow of the sural flap and
      were able to give recommendations as to the necessary pedicle width for the flap
      to be transferred safely. METHODS: The collateral bypass pathway of the small
      saphenous vein was studied in five formalin-preserved cadaver legs. The authors
      evaluated the usefulness of duplex sonography to visualize the venous collateral
      system of the small saphenous vein in five legs of healthy volunteers. RESULTS:
      The pedicle width necessary to bypass the small saphenous vein ranged from 1.4 to
      3.1 cm in the human cadavers and 0.09 to 1.5 cm in the duplex group. In both
      groups, only one side, medial or lateral to the small saphenous vein, was
      responsible for a total proximal-to-distal bypass. The opposite side partly
      bypassed the vein. Ultrasonography alone without Doppler was sufficient to
      visualize this variable suprafascial venous network. CONCLUSION: Preoperative
      evaluation of the venous system through duplex sonography is essential to
      localize on which side the bypass veins are present, making it possible to
      decrease the width of the pedicle without interfering with the reliability of the
      sural flap.

PMID- 18090754
TI  - Anatomical study of cutaneous venous flow of the sole.
AB  - BACKGROUND: It is well known that venous drainage of the medial plantar flap is
      performed by two venous systems: cutaneous veins visible through the skin that
      drain into the great saphenous vein; and deep veins, namely, accompanying veins
      of the medial plantar artery. However, there are only a few illustrations of the
      cutaneous veins of the sole in anatomical textbooks. Further clarification of the
      cutaneous veins of the sole was considered to be useful information in elevating
      the medial plantar flap. METHODS: Whole-body or local injection with contrast
      medium was performed in 10 fresh cadavers. The skin and subcutaneous tissue were
      elevated and radiographed with a soft x-ray system. In an embalmed cadaver,
      macroscopic observation was performed. RESULTS: In the sole, an intimate venous
      network was formed by branches of the great saphenous vein, small saphenous vein,
      and dorsal venous arch. Vascular arrangement of the venous network was not random
      but characteristic in each region of the sole. In the medial plantar, vessels
      were arranged toward the anterior margin of the medial malleolus. CONCLUSION: In
      planning the medial plantar flap, taking the vascular arrangement into
      consideration is considered to help the flap to avoid venous congestion and to
      extend the skin portion.

PMID- 18090755
TI  - A 12-year experience using the Brown two-portal endoscopic procedure of
      transverse carpal ligament release in 14,722 patients: defining a new paradigm in
      the treatment of carpal tunnel syndrome.
AB  - BACKGROUND: Compared with the open technique, endoscopic carpal tunnel release
      has a shorter postoperative recovery period but has been associated with an
      increased risk of iatrogenic injury. Because of morbidity of the open method,
      including painful scars, pillar pain, tendon adhesions, scar entrapment of the
      median nerve, chronic regional pain syndrome, and a longer postoperative recovery
      period, many patients have been treated nonoperatively to circumvent or forestall
      surgery, resulting in unrelieved median nerve compression and an increased risk
      of permanent nerve injury. METHODS: Inclusion criteria included a diagnosis of
      carpal tunnel syndrome based on history and physical examination and
      electrodiagnostic studies; failure of a short trial of conservative therapy; and
      advanced disease as evidenced by sensory, motor, or atrophic changes in the
      median nerve distribution. Exclusion criteria included prior surgery, wrist
      extension of less [corrected] than 40 degrees, mass within the carpal tunnel,
      Guyon's syndrome, and bony carpal tunnel abnormalities. Patients meeting these
      criteria were treated by the Brown two-portal endoscopic technique. RESULTS: A
      total of 14,722 patients were treated with the Brown endoscopic procedure. Eleven
      patients (0.07 percent) required conversion to an open procedure. There was one
      iatrogenic injury. Postoperative results were inversely related to the severity
      of the preoperative electrodiagnostic studies and the duration of symptoms
      regardless of the method of nonoperative treatment given. CONCLUSIONS: Operative
      decompression should be carried out promptly if symptoms have been present for 2
      months or longer, as the occurrence of permanent nerve damage has been noted
      within this time frame. The authors advocate use of the two-portal endoscopic
      technique as previously described by Brown et al. for this purpose.

PMID- 18090756
TI  - Flap resurfacing of postinfection soft-tissue defects of the hand.
AB  - BACKGROUND: Severe suppurative infections of the hand require antibiotics and
      excisional debridement for control and reversal. This sometimes results in large
      soft-tissue defects for which primary closure may not be possible. METHODS:
      Thirty-one patients had postinfection soft-tissue defects of the hand that were
      resurfaced using flaps. Small defects (<5 cm in greatest dimension) were found in
      22 patients, medium-sized defects (5 to 10 cm in greatest dimension) were found
      in four patients, and large defects (>10 cm in greatest dimension) were found in
      five patients. Type 2 diabetes mellitus was present in 48 percent. RESULTS: Flap
      survival was 100 percent. There was no flap necrosis or reactivation of
      infection. Patients regained functional use of the hand, and employed patients
      returned to work. CONCLUSIONS: Provided that infections have been well controlled
      by judicious surgical debridement and appropriate flap selection and technique is
      exercised, flap resurfacing can be performed safely and remains an important
      adjunct in the total management of hand infections. Benefits include the
      provision of a durable vascularized wound bed, which facilitates primary healing,
      restoration of gliding planes for exposed tendons and neurovascular structures,
      and provision of a stable platform for early mobilization and support of future
      reconstructive efforts if these are required.

PMID- 18090757
TI  - Vein grafts used as nerve conduits for obstetrical brachial plexus palsy
      reconstruction.
AB  - BACKGROUND: Limited availability of donor nerve grafts along with donor-site
      morbidity has stimulated research toward other alternatives for the repair of
      severe nerve injuries. The authors provide a comprehensive review of
      "tubulization" biology and share with the readers their experience with two cases
      of obstetrical brachial plexus paralysis where they used vein grafts with
      "minced" nerve tissue, to accomplish connectivity of proximal donors with distal
      targets. Usage of vascular tissue as conduits for nerve regeneration was first
      reported more than 100 years ago. It has been suggested that the vein's wall
      allows diffusion of the proper nutrients for nerve regeneration, acts as a
      barrier against ingrowth of scar, and prevents wastage of regenerating axons.
      METHODS: In this report, vein grafts of 2.4, 3.5, and 22 cm in length filled with
      minced peripheral nerve tissue were used as bridges in two cases of obstetrical
      brachial plexus paralysis. RESULTS: By filling the vein lumen with small pieces
      of nerve tissue suspended in a heparinized saline solution, a potential problem
      associated with vein collapse caused by compression was solved. CONCLUSION: The
      authors suggest that tubulization techniques should be kept in mind in clinical
      practice when autologous nerve grafts are insufficient for distal target
      connectivity or as an alternative to conventional nerve grafts for bridging
      certain nerve defects.

PMID- 18090758
TI  - Craniofrontonasal dysplasia: a surgical treatment algorithm.
AB  - BACKGROUND: Craniofrontonasal dysplasia is a rare, familial X-linked syndrome
      with coronal synostosis (brachycephaly or plagiocephaly), hypertelorbitism
      (frequently asymmetric), and extracranial anomalies. Details of the timing and
      technique of the craniofacial correction have not been well described. The
      largest series of patients with craniofrontonasal dysplasia treated at a single
      institution was used for review. METHODS: A review of patients at the University
      of California, Los Angeles Craniofacial Clinic with the diagnosis of
      craniofrontonasal dysplasia was performed (n = 21). Data included office,
      hospital, and operative records; photographs; lateral cephalograms; and three
      dimensional computed tomographic scans. Based on surgical outcomes, a treatment
      algorithm was created. RESULTS: Fourteen patients were female, seven were male,
      and five had a family history of craniofrontonasal dysplasia (24 percent). Eight
      patients had unilateral coronal synostosis (plagiocephaly) and 13 had bilateral
      coronal synostosis (brachycephaly). Eleven patients had asymmetric
      hypertelorbitism and 10 had symmetric hypertelorbitism. Patients also had cleft
      lip-cleft palate (10 percent), ear deformities (19 percent), strabismus or
      esotropia (81 percent), dry frizzy hair (100 percent), syndactyly (14 percent),
      and nail (100 percent) or other anomalies. After fronto-orbital advancement, no
      patients had increased intracranial pressure problems or difficulty related to
      resynostosis. After hypertelorbitism correction, three patients relapsed. Because
      of this, correction in later patients was delayed until after eruption of
      permanent maxillary incisors. The mean anterior interorbital distance was reduced
      in patients from 184 percent to 98 percent of sex-matched controls. CONCLUSIONS:
      The phenotypic expression of craniofrontonasal dysplasia is described to
      recognize patients early. A treatment algorithm for craniofrontonasal dysplasia
      based on timing and technique is offered to decrease the need for revision and
      improve outcomes.

PMID- 18090759
TI  - Optic nerve compression in craniofacial fibrous dysplasia: the role and
      indications for decompression.
AB  - BACKGROUND: Fibrous dysplasia is a benign bone disorder in which craniofacial
      bones are involved in approximately one-fifth of cases. Optic nerve compression
      is one of its most potentially devastating complications. The approach to visual
      disturbance caused by disease involvement of the optic canal has been varied and
      controversial. This is especially the case with regard to surgical decompression,
      particularly prophylactic decompression. METHODS: The authors performed a
      retrospective review of fibrous dysplasia patients who showed clinical or
      radiographic evidence of optic canal involvement over a 27-year period. RESULTS:
      Twenty-two optic canals in 18 patients were affected by disease. Of these, 14
      optic canals had symptoms (i.e., affected visual acuity or visual field). Twelve
      therapeutic and six prophylactic optic nerve decompressions were performed in
      total. At long-term follow-up (of at least 1 year), there was deterioration of
      vision in one-third of the patients who had undergone prophylactic decompression.
      Therapeutic decompression seemed to prevent visual deterioration in slightly more
      than half of the patients, with the majority having improvement in vision. There
      was visual deterioration in the remaining patients within this group, with most
      ultimately ending up with blindness. CONCLUSIONS: Therapeutic optic nerve
      decompression is advocated in patients with continuous deterioration of vision.
      Prophylactic decompression, in contrast, is not advised to be performed as a
      primary surgical procedure but as a procedure secondary to excision of lesion in
      the anterior skull base during the same operation.

PMID- 18090760
TI  - Bioactive glass hydroxyapatite in fronto-orbital defect reconstruction.
AB  - BACKGROUND: Synthetic bioactive ceramics and glasses have osteoconductive
      properties. These materials are capable of chemically bonding to the bone tissue.
      In addition, special bioactive glasses do not favor microbial growth. In this
      study, the clinical outcome of bioactive glass and hydroxyapatite in head and
      neck surgery was evaluated. METHODS: In a retrospective series of 150 patients,
      62 patients underwent reconstruction with frontal sinus obliteration after
      chronic frontal sinusitis, 65 patients were operated on for fronto-orbital
      traumas, and 23 patients underwent reconstruction after fronto-orbital tumor
      resections. These patients were evaluated for surgical procedures, reconstruction
      materials, complications, and functional outcomes. RESULTS: Three of the 62
      frontal sinus occlusions underwent operation (4.8 percent) during the follow-up
      of 5 years. The reoperations were caused by a new mucocele. In fronto-orbital
      reconstructions, we have reoperated on the orbital floor in four cases (7
      percent). All 12 benign tumor patients and six of 11 malignant tumor patients
      survived during a follow-up of 3 years. Two of the 23 (9 percent) complicated
      tumor and trauma patients underwent reoperation because of a local mucocele.
      CONCLUSIONS: Treatment of severe head and neck defects with biomaterial is a
      suitable alternative to conventional methods. Bioactive materials seem to be
      stable and reliable at clinical follow-up. The reconstructions with bioactive
      glass and hydroxyapatite are associated with good functional and aesthetic
      results without donor-site morbidity. However, more long-term outcomes of studied
      biomaterials are needed to determine whether they are capable of competing with
      traditional tissue grafts.

PMID- 18090762
TI  - Computer simulation of curvilinear mandibular distraction: accuracy and
      predictability.
AB  - BACKGROUND: The purpose of this study was to retrospectively evaluate the
      accuracy and reliability of a computer simulation system that predicts the
      results of an internal curvilinear mandibular distractor in the treatment of
      hemifacial microsomia and severe mandibular retrognathia. METHODS: A two
      dimensional computer analysis and simulation system was developed based on
      cephalometric radiographs and patient photographs. The software was used to
      generate and superimpose digital templates, corresponding to the actual
      distractor and logarithmic spiral, onto the lateral cephalometric tracings. The
      digital distractor's template was then adjusted to fit the radiographic
      projection of the actual distractor on the 1-week postoperative lateral
      cephalograph as precisely as possible. It was then activated along the spiral
      growth curve template until the ideal position of the mandible was reached. This
      computational surgical simulation tracing was then superimposed onto the actual
      postdistraction lateral cephalometric radiograph and tracing. Thus, the predicted
      and actual mandibular distraction movements were compared. RESULTS: In all of the
      cases, the computational distraction (skeletal and soft tissues) tracing fit the
      actual postdistraction tracing with an accuracy to within 1 mm. CONCLUSIONS: The
      current study demonstrated that a specific curvilinear distraction can (1)
      closely reproduce the natural logarithmic spiral movement of the mandibular
      growth, (2) be closely approximated and thus predicted by a computer simulation
      system, and (3) be used for correction of mandibular deformities such as
      hemifacial microsomia and severe mandibular retrognathia.

PMID- 18090763
TI  - Primary repair in adult patients with untreated cleft lip-cleft palate.
AB  - BACKGROUND: The authors have volunteered their services as plastic surgeons in
      several countries, such as Nepal and Cambodia. In these programs, the authors saw
      many adults with cleft lips or palates who could not have primary repair at the
      proper time. The purpose of this report is to discuss the primary repair of
      untreated cleft lips or palates in adult patients. METHODS: Subjects were older
      than 17 years. In Nepal, primary repairs were performed in 129 adults with
      untreated clefts over the past 11 years. Unilateral cleft lips were repaired by
      rotation advancement with the small triangular flap method or the straight method
      with a small triangular flap. Bilateral clefts were repaired using a one-stage
      repair method. Cleft palates were repaired by a mucoperiosteal push-back or
      Furlow technique. RESULTS: Differences between primary cleft repair for infants
      and for adults were as follows: (1) in adults, aggressive correction was
      possible, as maxillary growth was not a consideration; (2) correction of the
      anterior part of the nasal deformity was more difficult than in infants, as
      adults showed less elasticity and a more severe deformity of the nasal
      cartilages; (3) simultaneous palatoplasty should be chosen judiciously, as it is
      more invasive and results in higher morbidity; and (4) cheiloplasty under local
      anesthesia can reduce cost, time, and manpower. CONCLUSIONS: These observations
      should be useful for the local and foreign surgeons who treat clefts in
      developing regions.

PMID- 18090764
TI  - The cutting-edge technique for safe osteotomies in craniofacial surgery: the
      piezosurgery bone scalpel.

PMID- 18090765
TI  - Gross and pathologic analysis of long-term silicone implants inserted into the
      human body for augmentation rhinoplasty: 221 revision cases.
AB  - BACKGROUND: In augmentation rhinoplasty, delayed morphologic changes are often
      observed with silicone implants, despite them being known as a safe implant
      material. The purpose of this study was to identify the cause and time course of
      delayed shape changes of silicone implants, through the long-term evaluation of
      inserted implants and their surrounding nasal soft tissues after their removal at
      revision rhinoplasty operations. METHODS: Two hundred twenty-one silicone
      implants removed during revision rhinoplasty were studied. The period of
      insertion ranged from 1 month to 25 years, with an average of 6 years 7 months.
      Calcification within the silicone implants and, when available, the capsular soft
      tissue attachments were examined with the naked eye and light microscopy.
      RESULTS: Calcification was first observed grossly with the naked eye after 5
      years 8 months of insertion. With light microscopy, calcification debris could be
      seen after 4 years. After implant insertion for more than 9 years, focal
      calcification could be seen in 50 percent of implants. When implants had been
      inserted for more than 15 years, a denatured type of large calcification was
      clearly observed. Plasma cell, macrophage, and neutrophil proliferation was noted
      in the soft-tissue capsule surrounding the superficial calcifications in those
      individuals with an early inflammatory response, and lymphocyte proliferation was
      noted in those with a late inflammatory response. CONCLUSIONS: Silicone implants
      were noted to induce calcification when inserted for a long time, causing long
      term morphologic changes. This should be taken into consideration when choosing
      silicone implants for augmentation rhinoplasty.

PMID- 18090766
TI  - Modified tip grafts and tip punch devices.
AB  - BACKGROUND: Nasal tip aesthetics depend on the graceful synergism between soft
      tissue and the underlying frame. Nasal projection and the nasal tip width are the
      two most important components of nasal aesthetics. The cartilage graft, which has
      a predictable ability to affect several of the anatomical components contributing
      to nasal tip aesthetics, is one of the most versatile tools used to modify nasal
      projection. The fundamental shortcoming of the current graft sculpturing
      technique, namely, the requirement of time to create an optimal tip graft,
      prompted the design of a tool for the precise and rapid sculpturing of cartilage
      used for nasal tip onlay and shield grafts. METHODS: This report describes a
      modified design of the Peck and Sheen grafts and introduces a new instrument, the
      tip graft punch. The unique features of the tip graft punch that facilitate the
      production of a symmetric, precisely proportioned cartilage grafts are
      highlighted. RESULTS: The tip graft punch has been successfully used on 49
      patients over the past 2 years. CONCLUSIONS: The authors report a modification of
      nasal tip grafts and a simple and useful device for harvesting these grafts. This
      modification produces more natural and aesthetically pleasing results. The device
      saves surgery time, and provides a symmetric and anatomical graft design.

PMID- 18090767
TI  - Restylane and people of color.
AB  - BACKGROUND: Ethnic skin presents a unique paradox. Its melanin content provides
      protection from the sun, but the same skin can react to the slightest of
      injuries. The safety of Restylane in patients with increased susceptibility to
      keloid formation, hypertrophic scarring, hypersensitivity, and hyperpigmentation
      has not been studied. A retrospective review was used to determine whether
      Fitzpatrick skin types IV to VI are associated with an increased incidence of
      adverse outcomes related to Restylane use. METHODS: Sixty consecutive patients
      were injected with Restylane by a single surgeon (J.W.F.). Forty patients were
      categorized as Fitzpatrick skin types I to III and 20 as types IV to VI. Patient
      charts were reviewed for transient and permanent adverse outcomes related to
      Restylane injections, such as hypersensitivity, scar formation, altered
      pigmentation, and contour irregularities. All patients were evaluated at 2 to 4
      weeks and 6 to 9 months. RESULTS: The authors observed that 97.50 percent of the
      Fitzpatrick type I to III patients had no transient adverse outcomes related to
      Restylane injections. One patient experienced a 36-hour episode of exaggerated
      angioedema of the lips after injection, which resolved spontaneously. Another
      patient had an inclusion cyst that required incision and drainage and a 7-day
      course of antibiotics. None of the type I to III patients had permanent adverse
      outcomes related to Restylane. There were no transient or permanent adverse
      outcomes among the type IV to VI subjects. CONCLUSIONS: This study demonstrates
      that with proper and meticulous injection techniques, patients with Fitzpatrick
      skin types IV to VI can experience the same benefits of Restylane therapy as
      their lighter-complected counterparts.

PMID- 18090768
TI  - Laser ablation of unwanted hand veins.
AB  - BACKGROUND: Many patients express dissatisfaction with prominent and bulging hand
      veins. Abolishing these veins with sclerotherapy requires higher concentrations
      of sclerosing agents than are used for leg veins and often results in a tender,
      phlebitic cord. Phlebectomy is another treatment option. Endovenous occlusion and
      shrinkage techniques have been used successfully to treat varicose veins of the
      lower extremities. The authors demonstrate a new and unique endovenous laser
      technique to abolish unwanted hand veins. METHODS: Fifty-four hands (28 patients)
      with prominent hand veins were treated using a 600-microm laser fiber. The
      Dornier MedTech 940-nm diode laser system was used. The laser fiber was
      introduced through a 4-French sheath, which tracked as a coaxial system over an
      0.018-inch guidewire. Initial entry into the treated vein was accomplished with a
      20-gauge angiocatheter percutaneously. On average, four veins were treated in
      each hand. Tumescent anesthesia was infiltrated around the laser fiber/sheath
      unit before activating the laser, and all procedures were performed in an office
      setting. A compressive dressing was used postoperatively. RESULTS: All but one of
      the unwanted hand veins were cannulated successfully. The uncannulated vein was
      treated with sclerotherapy and eventually required phlebectomy. Hand swelling
      occurred in all treated hands and lasted 2 weeks or less. There was one skin burn
      of approximately 3 mm at a laser exit site. All 28 patients were satisfied with
      their results during follow-up, which ranged from 2 weeks to 31 months.
      CONCLUSIONS: This is the first report of endovenous treatment of unwanted hand
      veins. Laser ablation of unwanted hand veins can be performed in an office
      setting. These cosmetically conscious patients were satisfied with their results.

PMID- 18090769
TI  - The effects of angiotensin-converting-enzyme inhibitors on the fibrous envelope
      around mammary implants.
AB  - BACKGROUND: Late capsular contraction around breast implants is one of the most
      difficult complications to prevent or resolve. The authors studied the mechanisms
      that control the fibrotic process in an animal model. Using angiotensin
      converting enzyme inhibitors and angiotensin II receptor antagonist, the authors
      previously described a significant reduction in fibrosis in different
      experimental models. METHODS: Four groups of six rats each had a mini breast
      implant, 12 with a smooth surface and 12 with a textured surface. In two groups,
      the angiotensin-converting enzyme inhibitor enalapril was administered in
      drinking water, ad libitum, to determine its effect on both implant types. Two
      control groups were given plain drinking water. Three months postoperatively, all
      of the rats were killed and the capsule sections were cut and stained with
      hematoxylin and eosin and Masson's trichrome. Immunolabeling of collagen III and
      transforming growth factor (TGF)-beta1 was performed using monoclonal antibodies.
      RESULTS: Significant differences were found between smooth and textured implants,
      with a uniformly low inflammatory response found on textured implants. For both
      surfaces, the enalapril-treated group had a significant reduction of the
      inflammatory process that was especially marked in the textured implants.
      Immunostaining for collagen III and TGF-beta1 showed a consistent reduction in
      both fibrous tissue and cytokine mediator. CONCLUSIONS: Enalapril lowers the
      expression of fibrotic mediators, TGF-beta1, inflammatory markers, anti-ED1, anti
      collagen III monoclonals, and the periprosthetic fibrosis process. The reduction
      of TGF-beta1 indicates that the probable main cytokine mediator of the fibrotic
      cascade is attenuated. This hypothesis may provide the basis for a safe and cheap
      therapeutic strategy with which to modify the capsular contracture that sometimes
      affects women with mammary implants.

PMID- 18090770
TI  - The history of injectable silicone fluids for soft-tissue augmentation.
AB  - BACKGROUND: The debate over the legitimacy of silicone as a safe tool for soft
      tissue augmentation has spanned well over half a century. Proponents concede that
      injections of questionable purity and/or of massive quantities have produced
      unfavorable outcomes. They assert that in experienced hands with "injectable
      grade" silicone, there are very few problems. Despite these claims, the
      literature is replete with disastrous outcomes following silicone fluid
      injection, often many years after the initial treatment. METHODS: An extensive
      review of the English-language literature was conducted using MEDLINE. RESULTS: A
      comprehensive review of injectable silicones was completed, revealing the
      origins, misuses, early clinical trials, and support for and against the
      injection of silicone fluids for the augmentation of soft tissues. CONCLUSIONS: A
      better understanding of the history of injectable silicone fluids for soft-tissue
      augmentation can give insight into the pitfalls and complications surrounding its
      use. There has been an evolution in the technique and type of products used for
      soft-tissue augmentation. In its current use, silicone oil for permanent soft
      tissue augmentation could be a very powerful tool. There is some literature that
      supports the use of a small amount of purified, high-viscosity silicone oil;
      however, there has not been a single longitudinal study to date with appropriate
      follow-up data. The unanswered question remains: Are the risks worth the
      potential benefits of silicone oil as a permanent filler?

PMID- 18090773
TI  - The effect of herbal medicines on platelet function: an in vivo experiment and
      review of the literature.
AB  - BACKGROUND: Herbal medicines are used by a considerable number of surgical
      patients. An increased risk of bleeding, substantiated by anecdotal reports, has
      been attributed to the use of certain herbs, and numerous in vitro experiments
      have identified some herbal extracts as platelet inhibitors. The purpose of this
      investigation was to determine whether standard commercial preparations of
      commonly used herbal medicines have an effect on platelet function in vivo and,
      by extension, to provide clinical scientific evidence of the safety of their use
      in the perioperative period. METHODS: Five commercially available herbal agents
      were investigated, including Ginkgo biloba, garlic, Asian ginseng, St. John's
      wort, and saw palmetto. In a blinded fashion, one of the agents was administered
      to 10 adult volunteers at the manufacturer's recommended dose for 2 weeks. At the
      end of the 2-week period, in vivo platelet function was quantified using the PFA
      100 assay. After a 2-week "washout" period, the protocol was repeated using a
      different agent. This 4-week cycle was repeated for each of the five herbal
      agents, as well as the control agent aspirin. RESULTS: In vivo platelet function
      was not affected by the administration of any herbal agent and was markedly
      inhibited with the administration of aspirin. CONCLUSIONS: The herbal medicines
      investigated in this study do not affect platelet function in vivo. Neither this
      experiment nor a review of the literature supports the concern of perioperative
      bleeding in users of these herbal medicines.

PMID- 18090774
TI  - Pectoral etching: a method for augmentation, delineation, and contouring the
      thoracic musculature in men.

PMID- 18090775
TI  - The outcomes of outcome studies in plastic surgery: a systematic review of 17
      years of plastic surgery research.
AB  - BACKGROUND: The authors assessed the state of outcomes studies in plastic surgery
      since the initiation of the modern outcomes movement in 1988 and propose future
      research directions. METHODS: A systematic review of health outcomes research in
      plastic surgery was conducted. Studies were extracted from the journals Plastic
      and Reconstructive Surgery and Annals of Plastic Surgery from 1988 to 2004,
      yielding 3520 articles, 1670 of which did not meet the inclusion criteria; thus,
      1850 articles were reviewed. Studies were analyzed with respect to topic of
      interest, category of outcome study, study design, endpoint of results, and level
      of impact on health outcomes, rated on a scale of 1 to 4 using a revised version
      of the Agency for Healthcare Research and Quality's outcomes impact scale. A
      level 4 study demonstrates the greatest direct impact on patient outcomes.
      RESULTS: Ninety percent of studies had a level 1 impact; 10 percent had a level 4
      impact. Breast surgery was most represented, constituting 26 percent of studies.
      Morbidity and objective clinical outcomes were the most frequent endpoints, cited
      in 52 percent and 32 percent of studies, respectively. Economic analyses were the
      least frequently encountered outcome study category, represented in only 0.6
      percent of studies. CONCLUSIONS: Most studies in this review had a level 1
      impact, signifying that most outcomes studies in plastic surgery do not show a
      direct policy impact in patient outcomes. However, they are important in
      confirming the effectiveness of interventions already in clinical practice and
      raising new research questions. There is a need for more economic analysis
      research in plastic surgery outcomes studies.

PMID- 18090776
TI  - Revitalizing the training of clinical scientists in surgery.

PMID- 18090778
TI  - Impact factors and publication times for plastic surgery journals.
AB  - BACKGROUND: The purposes of the authors' analysis were to assess the values that
      plastic surgical journals demonstrate in terms of the standardized measures
      created by the Institute for Scientific Information's Journal Citation Report,
      and to assess the relationship between these values and the turnaround time of
      these journals. METHODS: The overall indexes of surgical journals were compared
      with those of journals in other fields of medicine using the following
      parameters: highest impact factor, average impact factor, cited half-life,
      immediacy index, and number of journals. Similarly, plastic surgery journals were
      compared with the highest ranking journals from various fields of surgery. In
      addition, an evaluation of all original articles published in 2005, assessing the
      time intervals from submission to publication, submission to acceptance, and
      acceptance to publication, was conducted for all plastic surgical journals and
      the highest ranking journals from various surgical fields listed in the Journal
      Citation Report. RESULTS: Plastic surgical journals demonstrated low overall
      index values and a greater elongation of their turnaround time in comparison to
      journals in other fields of surgery and medicine. CONCLUSIONS: The fact that the
      field of plastic surgery targets a rather specific and limited medical audience,
      and that plastic surgical articles usually get quoted by this audience, partly
      explains these values. Furthermore, the elongated turnaround time contributes to
      their endurance. Since plastic surgical journals cannot attract a broader medical
      audience, journals should speed up their publication times to help these values
      rise.

PMID- 18090779
TI  - Value of citation numbers and impact factors for analysis of plastic surgery
      research.
AB  - BACKGROUND: Citations of articles reflect their scientific relevance. The
      Institute for Scientific Information's impact factor measures the average number
      of citations to articles in a journal. Consequently, less-cited articles are
      credited for the impact that a few frequently cited articles had. Furthermore,
      the impact factor is only in regard to the citations received in the first 2
      years after publication, whereas most articles may be cited only after that
      period. The authors tested the relevance of the impact factor as a measure of the
      scientific value of articles. METHODS: The authors identified the 10 most-cited
      articles of four leading journals and calculated the pattern of their citations
      over the years. On the basis of the most significant change of regression
      coefficient in this pattern, they established the critical citable period and the
      number of citations received in the first 2 years as a fraction of the number of
      citations received during this period. RESULTS: The citation distribution was
      skewed. The critical citable period was 16 years, in which articles gathered 61.3
      percent of their total number of citations (range, 52.3 to 74.3 percent). The
      number of citations obtained in the first 2 years correlated well with the number
      of citations received in the critical citable period (Spearman rho = 0.60, p <
      0.001), but only 2.5 percent of the latter number was gathered during the first 2
      years (range, 1.2 to 4.0 percent). CONCLUSION: The impact factor is not an
      adequate indicator for the scientific relevance or impact of the individual
      articles the authors studied.

PMID- 18090781
TI  - Expert witness reform.
AB  - The legal system depends on the medical expert for evidence. Doctors readily
      complain about frivolous cases that go to trial, yet a lawyer cannot bring a
      frivolous claim to trial without a physician expert witness stating that the
      claim is not frivolous. An insurance company cannot raise premiums without
      medical expert witnesses servicing the increasing litigation against the insured.
      Physicians must look to themselves as a major contributor to rising malpractice
      insurance costs. For without the physician expert witness, no medical malpractice
      lawsuit can take place. It is the expert physician, not the attorneys or
      insurance companies, who defines "meritless" and "frivolous" and who ultimately
      controls the courts' medical malpractice caseload.

PMID- 18090782
TI  - Plastic surgery journals: a meeting of minds in Berlin.

PMID- 18090783
TI  - Looking back at 50 years of plastic surgery.

PMID- 18090784
TI  - Innovation.

PMID- 18090787
TI  - Preoperative osseous dysmorphology in unilateral complete cleft lip and palate.

PMID- 18090788
TI  - Reconstruction of neck scar contractures using supraclavicular flaps.

PMID- 18090789
TI  - The role of betadine irrigation in breast augmentation.

PMID- 18090790
TI  - The use of quantitative abductor pollicis brevis strength testing in patients
      with carpal tunnel syndrome.

PMID- 18090792
TI  - Factors impacting thromboembolism after bariatric body contouring surgery.

PMID- 18090795
TI  - Perforator-plus flaps: a new concept in traditional flap design.

PMID- 18090796
TI  - A free reverse preauricular flap for reconstruction of a nasal defect.

PMID- 18090797
TI  - Open techniques in closed rhinoplasty.

PMID- 18090798
TI  - Correction of the bra strap shoulder groove deformity in women.

PMID- 18090799
TI  - Asymptomatic spontaneous pneumothorax in anterior chest wall hypoplasia.

PMID- 18090800
TI  - Superior gluteal artery perforator flap reconstruction for anterior thoracic
      hypoplasia.

PMID- 18090801
TI  - Burns due to heating pads.

PMID- 18090802
TI  - Successful transfer of a vascularized fibular osteocutaneous bone graft harvested
      distal to a previously fractured fibula.

PMID- 18090803
TI  - Versatility of the gastrocnemius muscle flap: how high can you reach?

PMID- 18090804
TI  - Lower leg reconstruction using three free flaps.

PMID- 18090805
TI  - Lateral fold rotational flap technique for treatment of ingrown nail.

PMID- 18090808
TI  - Inamed silicone breast implant core study results at 6 years.
AB  - BACKGROUND: Silicone gel-filled breast implants were developed in 1962 but did
      not fall under the auspices of the U.S. Food and Drug Administration until 1976
      and were not classified as class III devices until 1988. This set the stage for a
      series of Food and Drug Administration advisory panel meetings and a moratorium
      on the sale of these implants from 1992 until 2006, when sufficient clinical data
      were presented to demonstrate their safety. METHODS: This study was conducted
      under the rigorous framework of a Food and Drug Administration-approved
      investigational device exemption to document the safety and effectiveness of
      Inamed silicone-filled breast implants through 10 years. Of 940 female subjects,
      approximately half were augmentation subjects, one-quarter were reconstruction
      subjects, and one-quarter were revision subjects. Follow-up visits were conducted
      at 0 to 4 weeks, 6 months, 1 year, and annually thereafter. Approximately one
      third of subjects also underwent biennial magnetic resonance imaging evaluation
      to detect silent rupture. Primary statistical analyses used the Kaplan-Meier
      product limit method. RESULTS: Data through 6 years are currently available from
      the 10-year study, with patient follow-up rates for that visit ranging from 78 to
      92 percent per cohort. As expected, the most common local complication in all
      cohorts was capsular contracture, occurring in 15 to 20 percent of subjects. The
      by-implant rupture rate was 3.5 percent overall at 6 years. Satisfaction with
      implants was uniformly high throughout the study period, with 6-year rates of 95
      percent for augmentation subjects and 94 percent for reconstruction subjects.
      CONCLUSION: Study results demonstrate the safety and effectiveness of Inamed
      silicone-filled breast implants through 6 years, including a low rupture rate and
      high satisfaction rate.

PMID- 18090810
TI  - The Mentor Core Study on Silicone MemoryGel Breast Implants.
AB  - BACKGROUND: In 2005, convincing safety and efficacy data were presented,
      resulting in the approval of Mentor MemoryGel Implants, with conditions. METHODS:
      The 1007 women enrolled in the 10-year, multicenter, Mentor Core MemoryGel Study
      were distributed into four cohorts: 551 primary augmentation patients, 146
      revision-augmentation patients, 251 primary reconstruction patients, and 59
      revision-reconstruction patients. Preoperatively and postoperatively, study
      instruments and physical examinations were administered to assess medical
      history, patient satisfaction, quality of life and body image, connective tissue
      disease diagnosis, rheumatology symptoms, and chest size change to determine the
      efficacy of surgery. RESULTS: Safety assessments included complication rates and
      rates of reoperation. Results at 3 years were reported at the U.S. Food and Drug
      Administration panel. Results indicate that the risk of any complication
      (including reoperation) at some point through 3 years after implant surgery is
      36.6 percent for primary patients, 50.1 percent for revision-augmentation
      patients, 49.4 percent for primary reconstruction patients, and 47.5 percent for
      revision-reconstruction patients. Suspected rupture rates reported from the
      magnetic resonance imaging cohort were 0.5 percent for primary augmentation, 7.7
      percent for revision-augmentation, 0.9 percent for primary reconstruction, and 0
      percent for revision-reconstruction. Only two implants, in a single patient, were
      found surgically to be ruptured. There were 4.7 percent primary and 12.3 percent
      revision-augmentation patients who had their implants removed, with patient
      choice and severe capsular contracture being the most common reasons. CONCLUSION:
      The data demonstrated safety and efficacy of the devices, but also indicate that
      a focus must be placed on better education and technique to improve clinical
      outcomes in the future.

PMID- 18090812
TI  - The Mentor Study on Contour Profile Gel Silicone MemoryGel Breast Implants.
AB  - BACKGROUND: Two-year safety and efficacy data were presented to the Canadian
      Therapeutic Products Directorate Scientific Advisory Panel, in Ottawa, Ontario,
      Canada. METHODS: The 955 women enrolled in the 10-year, multicenter, Mentor
      MemoryGel study were distributed into four cohorts: 572 augmentation patients,
      123 revision-augmentation patients, 191 reconstruction patients, and 69 revision
      reconstruction patients. The surgeons in the study received an intensive clinical
      educational program in addition to the protocol. RESULTS: Mentor's 2-year study
      results indicate that the risk of any complication or reoperation at some point
      through 2 years after implant surgery is 24.5 percent for primary augmentation
      patients, 30.2 percent for revision-augmentation patients, 42.9 percent for
      primary reconstruction patients, and 41.8 percent for revision-reconstruction
      patients. The rupture rates reported from the magnetic resonance imaging cohort
      were 0 percent for all groups. Patients reoperated on at least one time were as
      follows: 9.4 percent for primary augmentation, 12.8 percent for revision
      augmentation, 27.3 percent for primary reconstruction, and 19.4 percent for
      revision-reconstruction. Also, 2.4 percent of primary augmentation patients, 7.3
      percent of revision-augmentation patients, 8.9 percent of primary, and 11.6
      percent of reconstruction patients had their implants removed, with patient
      choice and capsular contracture being the most common reasons. CONCLUSIONS: The
      data from the Mentor CPG Gel Study resulted in approval of these implants for
      general use on October 20, 2006. The educational program resulted in improved
      clinical outcomes and probably should be required for all surgeons using the
      devices.

PMID- 18090814
TI  - The diagnosis of silicone breast implant rupture.
AB  - Magnetic resonance imaging of the breast in the diagnosis of silicone breast
      implant rupture is widely accepted to be the imaging study of choice for most
      women. Magnetic resonance imaging in the detection of silicone implant failure
      has been shown to have the highest sensitivity and specificity and has the
      ability to image the entire implant without the use of ionizing radiation.
      Unfortunately, some women are unable to have a magnetic resonance imaging
      examination of the breast because of contraindications such as cardiac
      pacemakers, aneurysm clips, and claustrophobia. Therefore, mammography,
      ultrasonography, and computed tomography will have roles in the diagnosis of
      silicone breast implant ruptures. This article illustrates the spectrum of
      imaging appearances of normal silicone gel implants and the appearances of
      silicone breast implant ruptures.

PMID- 18090813
TI  - Style 410 highly cohesive silicone breast implant core study results at 3 years.
AB  - BACKGROUND: In February of 2001, Allergan (formerly Inamed) began an
      Investigational Device Exemption study of a shaped breast implant: the Style 410
      highly cohesive silicone-filled breast implant. METHODS: Forty-eight plastic
      surgeons across the United States performed implantation on 941 subjects enrolled
      in a 10-year study. This prospective, nonrandomized study provided 3-year follow
      up data, clinical outcomes, and satisfaction rates from this cohort of 492
      primary augmentation, 225 breast reconstruction, and 224 breast revision
      subjects. Complications were reported and compared with those from current
      standard gel and saline implant studies. RESULTS: With greater than 85 percent
      follow-up compliance at 3 years, complication rates were low among augmentation
      subjects, with implant malposition being the most common (2.6 percent) and all
      other complications occurring in less than 2 percent of subjects. In the revision
      augmentation group, the most common complications were capsular contracture (4.8
      percent) and implant malposition (4.7 percent), with all other complications
      occurring in less than 4 percent. Asymmetry (8.7 percent) and capsular
      contracture (5.9 percent) were the only complications that occurred in more than
      5 percent of reconstruction subjects. The overall risk of rupture across all
      cohorts was 1.0 percent by subject and 0.8 percent by implant. Subject
      satisfaction with implants was 98 percent for augmentation and 90 percent or
      higher for all other cohorts. CONCLUSIONS: The Style 410 highly cohesive silicone
      implant has low complication rates and high satisfaction rates through 3 years
      after implantation. These results are significant in introducing more evidence
      based medicine that will allow plastic surgeons and patients to make better
      informed decisions regarding implant options.

PMID- 18090815
TI  - Breast implant rupture and connective tissue disease: a review of the literature.
AB  - BACKGROUND: Large-scale epidemiologic studies to date have not found any credible
      association between silicone breast implants and either well-defined connective
      tissue diseases or undefined or atypical connective tissue diseases. It has been
      hypothesized that implant rupture could prompt an immunologic reaction giving
      rise to autoimmune or related diseases. In this article, the authors review the
      available literature on implant ruptures and connective tissue disease. METHODS:
      Articles were identified from PubMed and by cross-checking reference lists of
      retrieved articles. RESULTS: Five publications were identified. In none of the
      studies were diseases or symptoms related to well-defined or ill-defined
      connective tissue diseases associated with rupture status. CONCLUSIONS: There
      appears to be little scientific basis for any association between implant rupture
      and well-defined connective tissue disease or undefined or atypical connective
      tissue diseases. The concept of silicone-related disease was developed by
      rheumatologists based on highly selected groups of symptomatic breast implant
      patients seen in their practices. It is likely that nonspecific complications or
      symptoms related perhaps to capsular contracture or implant rupture may be
      misinterpreted as representing a systemic disease.

PMID- 18090816
TI  - Breast implants and breast cancer: a review of incidence, detection, mortality,
      and survival.
AB  - Soon after breast implants were commercially introduced over 30 years ago,
      questions about potential carcinogenicity were raised. Animal experiments dating
      back to the mid-twentieth century demonstrated that foreign body implantation of
      many materials, including silicone, can induce sarcomas. Indeed, female breast
      cancer incidence rates in the United States have increased substantially over
      that period. Of the several published studies from various countries that have
      formally investigated the risk of breast cancer among augmentation mammaplasty
      patients, none show any evidence of increased risk. In fact, most find lower than
      expected risk, some with statistically significant reductions. Similarly, breast
      cancer mortality among these patients is generally found to be below that
      expected of other similar women. Delayed detection of breast cancer is a concern
      for these patients because implants can interfere with mammography. However,
      using indicators such as stage at diagnosis and tumor size, current research
      shows that augmentation patients do not experience delayed detection.
      Furthermore, several comparisons of post-breast cancer survival of augmented
      versus nonaugmented patients have found no significant differences. In summary,
      breast implants are not associated with an increased risk of breast cancer
      incidence or death, and these patients do not experience delayed detection or
      poorer post-breast cancer survival.

PMID- 18090817
TI  - The effect of silicone implants on the diagnosis, prognosis, and treatment of
      breast cancer.
AB  - BACKGROUND: Because of the prevalence of breast cancer, many augmented women
      eventually will develop the disease. This article reviews what is known about the
      effect of implants on the detection, prognosis, and treatment of carcinoma of the
      breast. METHODS: Observations were made on 4082 breast cancer patients (3953
      nonaugmented and 129 augmented) treated over a 23-year time span. Findings in the
      two groups were compared and differences analyzed statistically. Mammograms of
      all women with palpable lesions were reviewed to assess mammographic sensitivity
      in patients with and without implants. Cosmetic outcomes in augmented patients
      treated with breast conservation therapy were reviewed. RESULTS: Augmented
      patients presented more frequently with palpable lesions, invasive tumors,
      axillary nodal metastases, and false-negative mammograms. However, there was no
      significant difference in stage of disease, tumor size, recurrence rates, or
      survival between the two groups. Augmented patients treated with breast
      conservation therapy often experienced poor cosmetic results and frequently
      required reoperation. CONCLUSIONS: Despite the diminished sensitivity of
      mammography in women with implants, augmented and nonaugmented patients are
      diagnosed at a similar stage of disease and have a comparable prognosis. Implants
      may impair mammography but appear to facilitate tumor detection on physical
      examination. Magnetic resonance imaging and breast ultrasound may be useful
      adjuncts, but conventional mammography remains the most reliable tool for
      diagnosing early breast cancer in augmented patients. Breast implants do not
      interfere with mastectomy or breast reconstruction but may compromise the outcome
      of breast conservation therapy.

PMID- 18090818
TI  - The relationship of silicone breast implants and cancer at other sites.
AB  - BACKGROUND: Although most attention regarding the effects of silicone breast
      implants on cancer risk has focused on breast cancer, there have also been
      concerns regarding effects on other cancers. This includes malignancies that
      could occur as a result of foreign-body carcinogenesis (sarcomas) or immune
      alterations (hematopoietic malignancies), or cancers suggested as possibly
      elevated on the basis of previous epidemiologic studies (cancers of the cervix,
      vulva, lung, and brain). METHODS: Searches of the English language literature on
      the topic of silicone breast implants and cancer risk were conducted and reviewed
      to determine relationships that might have etiologic relevance. RESULTS:
      Epidemiologic studies provide no support for an increased risk of either sarcoma
      or multiple myeloma among breast implant recipients, disputing clinical and
      laboratory findings suggesting such a link. Although a number of epidemiologic
      studies have demonstrated elevated risks of cervical, vulvar, and lung cancers
      among breast implant patients, it is likely that these excesses relate more to
      lifestyle characteristics (e.g., cigarette smoking, sexual behavior) than to the
      effects of the implants. Brain cancer excesses, suggested in one study, have not
      been confirmed in either an update of the mortality experience in this study or
      on the basis of other investigations. CONCLUSIONS: At present, there is no
      convincing evidence that breast implants alter the risk of nonbreast
      malignancies. Breast implant patients should continue to be monitored for longer
      term risks and to assess whether cancer risk is influenced by various patient and
      implant characteristics.

PMID- 18090819
TI  - The psychological safety of breast implant surgery.
AB  - One positive consequence of the challenge to silicone breast implants has been
      renewed interest in the psychological dimensions of plastic surgery. When asked
      questions about the psychological outcomes of women with breast implants, plastic
      surgery responded with work that is changing the very framework on which concepts
      such as body image and quality of life are founded. In the course of exploring
      the psychological impact of breast augmentation, traditional ways of thinking
      about patient characteristics and motivations have been called into question.
      There is a new focus on evidence-based outcomes research and an active search for
      methods that are valid, reliable, and sensitive enough to recognize and measure
      the emotional impact of changing physical appearance. With more information about
      psychiatric comorbidities and the identification of variables that influence
      patients' attitudes, augmentation mammaplasty with implants is better understood.
      Meanwhile, a new generation of investigators has been stimulated to study and
      reinterpret the psychodynamics of the aesthetic surgery experience.

PMID- 18090820
TI  - The psychological aspects of cosmetic breast augmentation.
AB  - BACKGROUND: The psychological aspects of cosmetic breast augmentation have been
      the focus of a great deal of empiric study over the past 40 years. METHODS:
      Studies investigating the preoperative characteristics and psychosocial status of
      women interested in breast augmentation are reviewed. Investigations of
      postoperative satisfaction and psychosocial changes are discussed. The results of
      the seven epidemiologic studies that have identified a relationship between
      cosmetic breast augmentation and suicide are detailed. RESULTS: Methodologic
      limitations of the studies investigating the preoperative psychosocial status of
      breast augmentation candidates make it difficult to draw firm conclusions about
      the potential psychological differences between these women and those not
      interested in breast augmentation. Postoperative satisfaction rates are high, and
      several studies suggest that patients experience improvements in body image
      following surgery. The effects of breast augmentation on other areas of
      psychological functioning are less clear. Based on the seven epidemiologic
      studies published to date, the suicide rate among women with cosmetic breast
      implants is two to three times the expected rate. CONCLUSIONS: The literature in
      this area should be used to guide the psychosocial assessment and management of
      cosmetic breast augmentation patients. There currently is little evidence to
      support a recommendation that all women who present for cosmetic breast
      augmentation be required to undergo a psychiatric evaluation before surgery.
      Given the relationship between breast implants and suicide, however, it is
      recommended that women with a history of psychopathology who present for breast
      augmentation, or those who are suspected by the plastic surgeon of having some
      form of psychopathologic abnormality, should undergo a mental health consultation
      before surgery.

PMID- 18090821
TI  - Silicone breast implants and platinum.
AB  - Platinum, in a specific form, is used as a catalyst in the cross-linking
      reactions of the silicone gel and elastomer in breast implants. After
      manufacture, it remains in the devices at low-parts-per-million levels. Potential
      concerns have been raised as to whether this platinum might diffuse from silicone
      breast implants into the body and result in adverse health effects. The weight of
      evidence indicates that the platinum present is in its most biocompatible (zero
      valence) form, and the very minute levels (<0.1 percent) that might diffuse from
      the implants do not represent a significant health risk to patients.

PMID- 18090822
TI  - Breast-feeding and silicone implants.
AB  - BACKGROUND: Despite the overwhelming advantages of breast-feeding, there is a
      persistent concern that maternal exposure to chemical contaminants may result in
      contamination of breast milk and have an effect on the child's growth and
      development. A parallel concern regarding lactation in women with silicone
      implants over the past years has led to confusion and anxiety relating to the
      potential risks to the child. METHODS: The author reviewed the facts and issues
      as he knows them, including biomaterials, lactation toxicology, and a previous
      study where no difference was found in silicon (a proxy measurement of silicone)
      in women breast-feeding with silicone implants and those without. RESULTS: In the
      author's previous study, he compared women with implants to women without
      implants as controls and showed that mean silicon levels were not significantly
      different in breast milk (55.45 +/- 35 and 51.05 +/- 31 ng/ml, respectively) or
      in blood (79.29 +/- 87 and 103.76 +/- 112 ng/ml, respectively). However, silicon
      levels in alternative methods of infant nutrition were much higher. The mean
      silicon level measured in store-bought cow's milk was 708.94 ng/ml, whereas that
      for 26 brands of commercially available infant formula was 4402.5 ng/ml.
      CONCLUSIONS: In this review, the author looked only at silicon/silicone and did
      not address other potential contaminants that may be associated with silicone gel
      or the elastomer shell. This report may provide plastic surgeons and other
      healthcare workers with information regarding silicon/silicone for discussion
      with women with gel implants who are contemplating breast-feeding.

PMID- 18090823
TI  - Adverse health outcomes in offspring of mothers with cosmetic breast implants: a
      review.
AB  - BACKGROUND: To assess whether maternal cosmetic breast implants are associated
      with adverse health outcomes among offspring, the authors examined published
      findings of epidemiologic studies that addressed this hypothesis. METHODS: Four
      epidemiologic studies, all from Scandinavia, were identified. Women with breast
      implants were identified from existing public and private registers of patients,
      and their offspring were traced through nationwide population and birth
      registers. The studies included a total of 11,445 women with breast implants and
      3248 children born after the mothers' implantation procedures. Comparison was
      made with children born to mothers who had undergone other cosmetic surgery or
      general population controls. Outcomes under study were congenital malformations,
      hospitalization for esophageal and rheumatic disorders, and perinatal mortality.
      RESULTS: Overall, the studied outcomes were similar between children born to
      mothers with breast implants and children of controls, and between children born
      before and after maternal breast implantation. In the Danish studies,
      significantly elevated rates of esophageal disorders were observed for children
      born before (observed-to-expected ratio, 2.0; 95 percent confidence interval, 1.3
      to 2.8) but not after (observed-to-expected ratio, 1.3; 95 percent confidence
      interval, 0.5 to 2.9) the mother's breast implant surgery. Similar excesses were
      observed among control children born before and after maternal breast reduction.
      In the Swedish and Finnish studies, all risk estimates for malformations and
      perinatal health were close to unity. CONCLUSION: Rates of esophageal and
      rheumatic disorders, congenital malformations, and perinatal mortality and
      hospitalization were comparable between children born to mothers with breast
      implants and children born to mothers who had undergone other cosmetic surgery.

PMID- 18090824
TI  - What do women need to know and when do they need to know it?

PMID- 18090826
TI  - Resection of comminuted ulna head fragments with soft tissue reconstruction when
      associated with distal radius fractures.
AB  - Acute management of fractures involving the head and neck of the distal ulna
      associated with comminuted unstable fractures of the distal radius remains
      difficult and controversial. Fifteen consecutive such cases treated with combined
      external and internal fixation together with primary resection of comminuted
      distal ulna fracture fragments and reconstruction of the periosteal sleeve and
      triangular fibrocartilaginous complex are reviewed. At an average follow-up of
      5.8 years, all patients were assessed for range of motion, strength, pain and
      function, and radiographic appearance. All had a range of motion postoperatively
      of at least 85% of the opposite wrist in all planes. Average grip strength was
      88.6% of the contralateral wrist. Radiographic evaluation demonstrated no
      evidence of instability in any plane. There were no cases of subluxation of the
      distal ulna nor collapse of the ulnar side of the carpus. Those 7 patients
      studied arthrographically demonstrated an intact "water-tight" ulna-sided soft
      tissue sling, and all distal radius fractures healed primarily.

PMID- 18090827
TI  - Long-term outcome of replantation of proximal-third amputated arm: a worthwhile
      endeavor.
AB  - We report a successful replantation of a proximal-third avulsed left arm in a 26
      year-old female with maintenance of good functional, clinical, Short Form 36, and
      the Disabilities of the Arm, Shoulder, and Hand outcomes results at 10 years. An
      organized approach combining staged surgical reconstruction and intense hand
      therapy allowed for both successful replantation and outcome. There exist no
      clear guidelines in making the decision between replantation and revision
      amputation. Controversy regarding the value of upper limb replantation seems to
      increase with ascending levels of amputation. A case report cannot provide
      guidelines, but several points can be made that may be of help to hand surgeons
      confronting this uncommon situation. In a highly motivated patient with realistic
      expectation, a preoperatively intact functioning shoulder should be considered an
      indication for attempt at replantation. With further staged reconstruction, a
      helper arm can still be achieved even in an avulsion-type amputation. Current
      operative and perioperative aspects of microsurgical replantation and subsequent
      reconstruction are discussed.

PMID- 18090828
TI  - Forearm rebalancing in osteochondromatosis by radioulnar fusion.
AB  - Options for treatment of a skeletally immature child with forearm involvement
      from osteochondromatosis vary widely from natural history observation through
      ulnar distraction lengthening in combination radial and ulnar osteotomies. An
      important factor in surgical indications is the status of the radial head. In the
      presence of a radial head dislocation, particularly in a very young child,
      radioulnar diaphyseal fusion (single-bone forearm) is a viable surgical option.
      It restores axial alignment, corrects proximal and distal radioulnar joint
      dislocations by resection, maintains forearm growth through the distal radius,
      and provides a stable elbow with a restoration of motion in a single-stage
      procedure.

PMID- 18090829
TI  - Dynamic stabilization of chronic scapholunate dissociation with palmaris longus
      transfer: a new technique.
AB  - This report presents a new procedure of palmaris longus tendon transfer to the
      scaphoid and lunate, with reconstruction of the scapholunate ligament in chronic
      scapholunate dissociation. From 1988 to 2006, 10 cases of dynamic stabilization
      of chronic scapholunate dissociation were treated by palmaris longus tendon
      transfer to the scaphoid and lunate. The tendon transfer to the scaphoid and the
      reconstructed scapholunate ligament appeared to create a resultant force that
      corrected the scaphoid drift. The transfer to the lunate neutralized its dorsal
      intercalary segment instability posture. A normal scapholunate interval was
      restored at about 2 years postoperatively, and the lunate malrotation remained
      permanently corrected. Recovery of the scapholunate interval paralleled the
      recovery of the scapholunate angle and grip strength. These remained unchanged
      with long-term follow-up of between 3 and 18 years. The tendon transfer appeared
      to function like other tendon transfers in the upper extremity, providing active
      stabilization of the scaphoid and the lunate despite increasing loads on the
      wrist. Unfortunately, in the absence of symptoms of peripheral nerve entrapment,
      insurance approval could not be obtained for electromyography studies to document
      the activity of the transferred tendon. The forces of tendon transfer on the
      scaphoid and the reconstructed scapholunate ligament seem to generate a resultant
      force that acted on the scaphoid to maintain it in its fossa. The tendon transfer
      to the lunate corrected the dorsal intercalary segment instability orientation of
      the lunate at long-term follow-up of up to 18 years.

PMID- 18090830
TI  - Free medial femoral condyle bone grafting for scaphoid nonunions with humpback
      deformity and proximal pole avascular necrosis.
AB  - Treatment of scaphoid nonunions remains a challenging problem, especially in the
      setting of proximal pole avascular necrosis or humpback deformity. Conventional
      bone grafting techniques have demonstrated unpredictable results in the setting
      of collapse deformities, whereas pedicled dorsal distal radius vascularized bone
      grafts have recently been reported to have nearly a 50% failure rate when used in
      scaphoid nonunions with proximal pole nonunion. Free vascularized medial femoral
      condyle bone grafting is one option for the treatment of scaphoid nonunions with
      proximal pole avascular necrosis associated with a humpback deformity. The
      indications, contraindications, and technique of free vascularized medial femoral
      condyle bone grafting are presented for the treatment of scaphoid nonunions
      associated with proximal pole avascular necrosis and humpback deformities.

PMID- 18090831
TI  - The versatile reverse-flow digital artery cross-finger flap.
AB  - Various flaps have been described for the reconstruction of the soft tissue
      defects of the digits, but these are not applicable to all kinds of defects.
      Moreover, these techniques are mostly 2-staged operations that require long-term
      immobilization. In this study, reverse-flow digital artery cross-finger flap was
      used to cover various volar and dorsal digital defects in 9 cases. Seven of 9
      cases that had follow-up period longer than 2 years were evaluated, and all had
      good results. We recommend that reverse-flow digital artery cross-finger flap is
      a universal flap that can be used for almost all types of soft tissue defects of
      the digits.

PMID- 18090832
TI  - Tenodermodesis for chronic mallet finger deformities in children.
AB  - The treatment of chronic mallet finger deformities in children can be
      challenging. Previously proposed for the treatment of chronic mallet fingers in
      adults, tenodermodesis is a reconstructive procedure that may also be applied to
      the pediatric population. The technique of tenodermodesis for chronic mallet
      finger injuries in children is presented here, featuring careful repair of the
      extensor mechanism and temporary transarticular Kirschner wire fixation of the
      distal interphalangeal joint. Preliminary clinical results with this procedure
      have been encouraging, with high patient/parent satisfaction and few
      complications. Most importantly, tenodermodesis allows anatomical reconstruction
      of the injured extensor mechanism while preserving skeletal growth and distal
      interphalangeal joint motion in children and adolescents.

PMID- 18090834
TI  - Polycystic ovary syndrome: clinical and imaging features.
AB  - Polycystic ovary syndrome is the most common endocrine disorder occurring in
      reproductive-age women. The syndrome is complex, multifactorial, and not always
      easily defined. Diagnosis is based upon a combination of clinical and biochemical
      criteria and ovarian morphology. The following review describes the clinical
      features, pathophysiology, diagnosis, and the role of imaging. Diagnostic imaging
      techniques are discussed, with emphasis on ultrasound as the main modality used
      worldwide. Contributions of 3-dimensional and Doppler ultrasound are addressed in
      addition to potential indications for magnetic resonance imaging in the
      evaluation of patients with suspected polycystic ovary syndrome.

PMID- 18090835
TI  - Liver transplantation: vascular complications.
AB  - Transplantation has become the method of choice for treatment of patients with
      irreversible severe liver dysfunction. Vascular thrombosis or stenosis, biliary
      obstruction, hemorrhage, posttransplantation neoplasm, and rejection are some of
      the most common potential complications. Most complications cause significant
      morbidity and mortality after liver transplantation. The appearance of vascular
      complications in posttransplantation patients is illustrated in this article.

PMID- 18090836
TI  - Imaging and estimation of tissue elasticity by ultrasound.
AB  - Ultrasound (US) elasticity imaging is an extension of the ancient art of
      palpation and of earlier US methods for viewing tissue stiffness such as
      echopalpation. Elasticity images consist of either an image of strain in response
      to force or an image of estimated elastic modulus. There are 3 main types of US
      elasticity imaging: elastography that tracks tissue movement during compression
      to obtain an estimate of strain, sonoelastography that uses color Doppler to
      generate an image of tissue movement in response to external vibrations, and
      tracking of shear wave propagation through tissue to obtain the elastic modulus.
      Other modalities may be used for elasticity imaging, the most powerful being
      magnetic resonance elastography. With 4 commercial US scanners already offering
      elastography and more to follow, US-based methods may be the most widely used for
      the near future. Elasticity imaging is possible for nearly every tissue. Breast
      mass elastography has potential for enhancing the specificity of US and
      mammography for cancer detection. Lesions in the thyroid, prostate gland,
      pancreas, and lymph nodes have been successfully imaged using elastography.
      Evaluation of diffuse disease including cirrhosis and transplant rejection is
      also possible using both imaging and nonimaging methods. Vascular imaging
      including myocardium, blood vessel wall, plaque, and venous thrombi has also
      shown great potential. Elasticity imaging may also be important in assessing the
      progress of ablation therapy. Recent work in assessing porous materials using
      elastography suggests that the technique may be useful in monitoring the severity
      of lymphedema.

PMID- 18090837
TI  - Detection and characterization of renal masses by ultrasound: a practical guide.
AB  - In this paper, we review classification schemes of renal cystic lesions, recent
      technical improvements helpful for improving radiologist confidence, the
      potential use of microbubble contrast agents, the differential diagnosis of solid
      renal lesions, and the expanding role of ultrasound-guided biopsy and treatment
      of renal masses.

PMID- 18090838
TI  - Renal vascular imaging: ultrasound and other modalities.
AB  - Sonographic evaluation of the genitourinary system is a fast, safe, and effective
      means to detect renal disease. In conjunction with other modalities, Doppler can
      depict a variety of abnormalities. However, optimization of Doppler techniques
      and a solid understanding of Doppler threshold criteria are critical for success,
      whether in the native or transplanted kidney.

PMID- 18090860
TI  - A quality-effects model for meta-analysis.
AB  - We introduce a quality-effects approach that combines evidence from a series of
      trials comparing 2 interventions. This approach incorporates the heterogeneity of
      effects in the analysis of the overall interventional efficacy. However, unlike
      the random-effects model based on observed between-trial heterogeneity, we
      suggest adjustment based on measured methodological heterogeneity between
      studies. We propose a simple noniterative procedure for computing the combined
      effect size under this model and suggest that this could represent a more
      convincing alternative to the random effects model.

PMID- 18090861
TI  - Association between intussusception and tonsil disease in childhood.
AB  - BACKGROUND: Intussusception is the most common cause of intestinal obstruction in
      infancy and early childhood, but its etiology remains unknown. The present study
      analyzes whether some children with intussusception subsequently have a higher
      risk of tonsil disease, suggesting an enhanced tendency to lymphoid hyperplasia.
      METHODS: This nationwide cohort study included all Danish children younger than
      age 15 years, who were born in 1977-2001 and diagnosed with intussusception at a
      hospital (n = 2018). The cohort was followed-up for tonsil disease in the Danish
      National Patient Registry and the Danish Health Security System. RESULTS: A total
      of 172 children were identified with tonsil disease following intussusception.
      The risk of tonsil disease was 48% higher (95% confidence interval = 27%-72%)
      after intussusception compared with the general population of the same age. Age,
      sex, age at intussusception, and time since intussusception did not modify risk
      of tonsil disease. The risks of acute tonsillitis, chronic disease of the
      tonsils, and tonsillectomy were equally increased after intussusception.
      CONCLUSIONS: Intussusception was associated with an increased risk of tonsil
      disease in childhood. Children with a general tendency to lymphoid hyperplasia
      may be at increased risk of intussusception.

PMID- 18090862
TI  - Prognostic value of electroneurography and electromyography in facial palsy.
AB  - OBJECTIVES: To compare the prognostic value of electroneurography (ENG) and
      needle electromyography (EMG) to estimate facial function outcome after acute
      facial palsy. STUDY DESIGN: Retrospective study using electrodiagnostic data and
      medical chart review. METHODS: Two hundred one patients treated 1995 to 2004 were
      included. Initial and final facial function was established clinically by the
      House-Brackmann (HB) scale. ENG results were classified into amplitude loss less
      than 75% and amplitude loss 75% or greater to predict complete recovery and
      defective healing, respectively. Initial and follow-up EMG results were
      classified into neurapraxia and predicted complete recovery. In contrast,
      axonotmesis/neurotmesis and mixed lesions predicted, by definition, defective
      healing. RESULTS: : Initial HB was II to IV in 154 patients and V to VI in 47
      patients. The etiology was idiopathic palsy in 139, iatrogenic lesion in 29,
      traumatic in 18, and herpes zoster in 15 patients. Finally, 134 (67%) patients
      showed a full recovery. Sixty-seven (33%) patients showed signs of defective
      healing. ENG presented a sensitivity, specificity, accuracy, positive predictive
      value (to predict defective healing), and negative predictive value of 60%, 79%,
      73%, 59%, and 80%, respectively. The values for the initial EMG were 66%, 98%,
      89%, 91%, and 89%. The best results showed the follow-up EMG with 85%, 100%, 97%,
      100%, and 96%. EMG results were not classifiable in 32 (16%) patients.
      CONCLUSIONS: EMG showed higher prognostic values than ENG, especially when
      repeated during the time course of the facial palsy. ENG might be helpful if the
      EMG result is not classifiable.

PMID- 18090863
TI  - Ototoxicity of triethanolamine polypeptide (cerumenex) in the chinchilla.
AB  - The use of earwax softeners and cerumenolytics to unblock the external auditory
      canal is increasing. Although reports on their effectiveness are available, data
      about their effect on hearing are limited. OBJECTIVE: To assess the effect of
      ototopic triethanolamine polypeptide oleate condensate 10% (Cerumenex) on
      hearing. STUDY DESIGN: Prospective, randomized, controlled trial in a chinchilla
      animal model. METHODS: Tympanostomy tubes were inserted in five chinchillas, and
      hearing was assessed with distortion product otoacoustic emissions (DPOAE)
      between 1 and 9 kHz prior to application and at days 1, 4, 30, and 100
      postototopic application of Cerumenex. One ear received Cerumenex; the other ear
      served as control. Postmortem scanning electron microscopy was performed to
      assess the cochlear hair cells. RESULTS: A reduction in the mean DPOAE signal was
      shown in the ears treated with Cerumenex from the first day after treatment and
      throughout the study. Almost all tested frequencies were affected. Swelling,
      crusting, and fluid were observed in four of the five experimental ears. One
      animal also developed facial paralysis in the experimental side. Electron
      microscopy showed damage of the outer and inner hair cells in the Cerumenex
      treated ears. CONCLUSIONS: In the chinchilla, when a tympanic perforation is
      present, Cerumenex causes a reduction in DPOAE signal and damage to the cochlear
      hair cells. Caution should be observed when prescribing this agent if the status
      of the tympanic membrane is unknown. Furthermore, its use without medical
      prescription should be discouraged because of the risk of ototoxicity and severe
      inflammatory reaction.

PMID- 18090864
TI  - In vitro activity of mupirocin on clinical isolates of Staphylococcus aureus and
      its potential implications in chronic rhinosinusitis.
AB  - BACKGROUND: It has been postulated that bacterial biofilms are involved in the
      pathogenesis of chronic rhinosinusitis (CRS). Biofilms present on sinus mucosa
      are difficult to eradicate with conventional antibiotic therapy and are thought
      to provide a nidus for recurrent infection. Topical delivery of antibiotics via
      nasal irrigation may present a way of delivering high concentrations of
      antibiofilm agents with potentially low systemic absorption and side effects.
      This study investigates the effectiveness of mupirocin and two other antibiotics,
      ciprofloxacin and vancomycin, on established in vitro biofilms of Staphylococcus
      aureus isolated from patients with CRS. METHODS: S. aureus American Type Culture
      Collection 25923 and 12 clinical isolates were investigated for their ability to
      form biofilms in an in vitro setting using a 96 well microtiter crystal violet
      (CV) plate assay and confocal scanning laser microscopy (CSLM). Antimicrobial
      susceptibility tests to determine minimum inhibitory concentrations were
      performed on planktonic and biofilm forming strains. In addition, established
      biofilms were subjected to the antimicrobial agents at a twofold dilution series.
      A CV analysis of biofilm mass was performed after 1 and 24 hours of treatment,
      and minimum biofilm inhibition concentrations at 50% (MIB50) and 90% (MIB90)
      biofilm inhibition were recorded. RESULTS: With use of a 96-well microtiter plate
      CV assay, 8 of the 12 clinical isolates formed mature biofilms after 8 days of
      culture. These results correlated with findings from CSLM analysis of in vitro
      biofilms grown on Permanox chamber slides. Increased antimicrobial resistance was
      observed in the biofilm isolates when compared with planktonic counterparts.
      Mupirocin was capable of reducing biofilm mass by greater than 90% at
      concentrations of 125 mug/mL or less in all S. aureus isolates. Ciprofloxacin and
      vancomycin were largely ineffective in attaining MIB90 concentrations within safe
      dosage ranges. CONCLUSIONS: The topical application of mupirocin via nasal
      irrigation may be useful in eliminating S. aureus biofilms present on the sinus
      mucosa of patients with CRS and may offer an additional treatment to patients
      with recalcitrant sinusitis.

PMID- 18090865
TI  - Temporal bone study of trisomy 13 syndrome.
AB  - The temporal bones of a 23-week-old female who had multiple congenital anomalies
      and bilateral hearing loss with trisomy 13 syndrome were evaluated under light
      microscopy. In the left cochlea, spiral ganglion cells and cochlear nerve fibers
      are absent. In the right ear, an abnormal branch of the singular nerve passes
      between the utricle and lateral semicircular canals and separates the two
      portions, one to the flattened crista of the lateral semicircular canal, the
      other to the utricular macula. This is a rare report describing a patient with
      abnormalities in three nerves, including the facial, vestibular, and cochlear
      nerves.

PMID- 18090866
TI  - Obstructive sleep apnea in an infant with prominent glossopharyngeal muscles:
      therapy and outcome.
AB  - We present a case of prominent glossopharyngeal muscles causing severe
      obstructive symptoms in a 3-month-old child. Preoperative sleep studies and
      dynamic microdirect laryngoscopy were used in evaluation of the patient.
      Postoperative sleep studies confirmed a substantial reduction in apneic events
      after release of the muscle folds. The literature addresses the variant anatomy,
      and treatment options are discussed. To our knowledge, this is the first case
      report of prominent glossopharyngeal muscles leading to apneic events. We propose
      that in patients with prominent glossopharyngeal folds, surgical release may
      significantly improve symptoms of sleep apnea and in severe cases prevent
      tracheostomy.

PMID- 18090867
TI  - Temporal relationship between antitumor necrosis factor-alpha antibody therapy
      and recrudescence of head and neck squamous cell carcinoma.
AB  - Tumor necrosis factor (TNF)-alpha inhibitors have been used effectively to treat
      rheumatoid arthritis and inflammatory bowel disease. Although the role of TNF
      alpha in tumor development is not well understood, an increased risk of
      malignancies with anti-TNF-alpha therapy has been suggested. We report an
      instructive case of a patient, treated for Crohn's disease with infliximab, who
      presented with a neck abscess diagnosed to be head and neck squamous cell
      carcinoma. The patient's clinical course illustrates a temporal relationship
      between reappearance of his cancer after a complete response to therapy and the
      resumption of infliximab for worsening Crohn's disease.

PMID- 18090868
TI  - Otolaryngologist-head and neck surgeon-performed ultrasonography for parathyroid
      adenoma localization.
AB  - OBJECTIVE: To demonstrate the efficacy of otolaryngologist-head and neck surgeon
      performed ultrasonography (US) for the preoperative localization of parathyroid
      adenomas. METHODS: A retrospective chart review of all patients evaluated by
      office-based US for the localization of surgery-proven parathyroid adenomas from
      October 2004 through February 2007. RESULTS: A total of 29 patients underwent
      preoperative US localization. Twenty-three (79%) were females, and six (21%) were
      males. The age of patients ranged from 27 to 85 years of age. The size range of
      adenomas detected as measured by US was 0.5 to 2.7 cm. Pathology specimen
      measurements ranged from 0.3 to 3.4 cm. A total of 30 parathyroid adenomas were
      found. US identified 90% of the parathyroid adenomas to the correct side, left or
      right. In addition, US localized the parathyroid adenomas to the correct
      quadrant, superior or inferior, 83% of the time. Challenges in accurate
      localization were associated with patient obesity, presence of thyroid carcinoma,
      and multinodular thyroid disease. For comparison, sestamibi scans performed on
      the same patients localized the parathyroid adenoma to the correct side only 71%
      of the time and to the correct quadrant 61% of the time. CONCLUSIONS:
      Otolaryngologist-head and neck surgeon-performed US can accurately identify the
      location of parathyroid adenomas and is a useful tool for preoperative planning.

PMID- 18090869
TI  - Long-term results of Provox ActiValve, solving the problem of frequent candida-
      and "underpressure"-related voice prosthesis replacements.
AB  - OBJECTIVES: To assess the long-term results of the Provox ActiValve, a prosthesis
      for voice rehabilitation after total laryngectomy that was designed to lessen the
      need for frequent replacements caused by Candida and "underpressure." PATIENTS
      AND METHODS: Retrospective assessment of device lifetime, indications for
      replacement, voice quality, and maintenance issues, measured by a structured
      trial specific questionnaire, in a cohort of 42 laryngectomized patients,
      experiencing a short Provox2 device lifetime (median, 21 days). RESULTS: The
      median device lifetime of Provox ActiValve, replaced for leakage through the
      device and those still in situ at the date of data collection (N = 32), was 337
      days (mean 376 days): a statistically significant 16-fold increase compared to
      the Provox2 prosthesis (P < .001). In 10 patients, replacement was fistula
      related (median after 86 days): esophageal pouch (N = 4), fistula granulation (N
      = 3), extrusion of the device (N = 2), and periprosthetic leakage (N = 1). Eighty
      six percent of the patients used a special lubricant to diminish "stickiness" of
      the valve. Provox ActiValve was preferred by 90% of the patients who completed
      the trial-specific questionnaire. CONCLUSIONS: For patients requiring frequent
      device-related replacements, Provox ActiValve, also long-term, provides a true
      solution and thereby is a valuable addition to prosthetic voice rehabilitation.

PMID- 18090870
TI  - Dual action of TGF-beta1 on nasal-polyp derived fibroblasts.
AB  - OBJECTIVES: Transforming growth factor beta-1 (TGF-beta1) is a known fibrogenic
      factor with immunosuppressive properties. We wanted to determine the effect of
      stimulation with TGF-beta1 on nasal polyp-derived fibroblasts and assess the role
      this molecule would have in polyp formation and growth. STUDY DESIGN: Nasal-polyp
      derived fibroblasts were cultured with or without TGF-beta1, and proliferation
      and cytokine secretion were measured. METHODS: Fibroblasts were isolated from
      nasal polyps following endoscopic surgery. Cells were plated and grown until
      confluent, after which they were split and used in assays. Cells were stimulated
      with TGF- beta1 and mRNA collected after 16 hours, supernatants after 72 hours,
      and proliferation measured after 96 hours of culture. RESULTS: TGF-beta1
      significantly (P < .02) increased proliferation of nasal-polyp derived
      fibroblasts. We examined the expression of inflammatory cytokines and found that
      TGF-beta1 decreased expression of CCL2 (MCP-1), CCL5 (RANTES), CCL11 (eotaxin),
      granulocyte-colony stimulating factor (G-CSF), and GM-CSF (P < .05). In contrast,
      incubation with TGF-beta1 increased fibronectin, procollagen, vascular
      endothelial growth factor (VEGF), and TGF-beta2 protein production (P < .05). For
      select samples, we confirmed that the increased protein production was due to
      increased mRNA expression. CONCLUSION: These studies suggest that TGF-beta1
      expression in polyp tissue can have dual effects. One role is to act as an anti
      inflammatory agent shown by the ability to inhibit pro-inflammatory mRNA and
      protein production. At the same time, TGF-beta1 expression leads to increases in
      factors involved in fibrosis and angiogenesis, promoting remodeling and cell
      growth.

PMID- 18090871
TI  - Evolution in the assessment and management of trigeminal schwannoma.
AB  - EDUCATIONAL OBJECTIVE: At the conclusion of this presentation, the participants
      should be able to understand the contemporary assessment and management algorithm
      used in the evaluation and care of patients with trigeminal schwannomas.
      OBJECTIVES: 1) Describe the contemporary neuroradiographic studies for the
      assessment of trigeminal schwannoma; 2) review the complex skull base osteology
      involved with these lesions; and 3) describe a contemporary management algorithm.
      STUDY DESIGN: Retrospective review of 23 cases. METHODS: Chart review. RESULTS:
      From 1984 to 2006, of 23 patients with trigeminal schwannoma (10 males and 13
      females, ages 14-77 years), 15 patients underwent combined transpetrosal
      extirpation, 5 patients underwent stereotactic radiation, and 3 were followed
      without intervention. Of the 15 who underwent surgery, total tumor removal was
      achieved in 9 patients. Cytoreductive surgery was performed in six patients; of
      these, four received postoperative radiation. One patient who underwent primary
      radiation therapy required subsequent surgery. There were no deaths in this
      series. Cranial neuropathies were present in 14 patients pretreatment and
      observed in 17 patients posttreatment. Major complications included meningitis
      (1), cerebrospinal fluid leakage (2), major venous occlusion (1), and temporal
      lobe infarction (1). CONCLUSIONS: Trigeminal schwannomas are uncommon lesions of
      the skull base that may occur in the middle fossa, posterior fossa, or both.
      Moreover, caudal extension results in their presentation in the infratemporal
      fossa. Contemporary diagnostic imaging, coupled with selective use of both
      surgery and radiation will limit morbidity and allow for the safe and prudent
      management of this uncommon lesion.

PMID- 18090872
TI  - B-type natriuretic peptide after hormone therapy in postmenopausal women with
      chest pain and normal coronary angiogram.
AB  - OBJECTIVES: Coronary heart disease is relatively uncommon in premenopausal women
      but shows a sharp increase after menopause. The decline of endogenous ovarian
      hormones is commonly assumed to be a major component of this phenomenon. The
      effects of estrogens on the vasculature have been investigated extensively in
      previous studies. However, the effects of estrogens on myocardial function have
      not been evaluated in humans. We sought to examine the effects of hormone therapy
      (HT) on myocardial function and cardiac natriuretic peptides in postmenopausal
      women with chest pain and a normal coronary angiogram. DESIGN: Transdermal HT
      (estradiol: 0.72 mg/2 d) was administered to 15 postmenopausal women with chest
      pain and a normal coronary angiogram (mean age, 53 y) for 12 weeks, and oral HT
      (conjugated equine estrogens: 0.625 mg/d) was administered to another 15
      postmenopausal women (mean age, 54 y) for 12 weeks. Echocardiography or cardiac
      catheterization showed no cardiac dysfunction in any woman at baseline. Cardiac
      function was evaluated by echocardiography, and plasma B-type natriuretic peptide
      was measured every 4 weeks. RESULTS: B-type natriuretic peptide levels increased
      after transdermal HT (baseline: 13.1 +/- 3.1, 4 wk: 22.1 +/- 2.9, 8 wk: 33.2 +/-
      3.1, 12 wk: 38.4 +/- 3.3 pg/mL; P < 0.01 vs baseline). The levels were also
      augmented after oral HT (baseline: 14.1 +/- 3.8, 4 wk: 23.2 +/- 3.3, 8 wk: 35.6
      +/- 3.9, 12 wk: 39.6 +/- 3.5 pg/mL; P < 0.01 vs baseline). Serial
      echocardiography showed no changes in ventricular function in either treatment
      group. At baseline the serum estradiol levels in the transdermal group were
      comparable with those in the oral group. CONCLUSIONS: The estradiol levels after
      HT increased in both groups, but there was no significant difference between the
      two groups. B-type natriuretic peptide levels increased without cardiac
      dysfunction, and the chest symptoms were relieved in some participants after HT.
      Thus, estrogen supplementation augments natriuretic peptide levels without
      harmful effects on ventricular function.

PMID- 18090873
TI  - The effects of abuse on health problems in menopausal women.

PMID- 18090875
TI  - Morbidity and mortality among patients with hip fractures surgically repaired
      within and after 48 hours.
AB  - OBJECTIVE: The objectives were (1) to compare the morbidity and mortality of
      patients with hip fractures surgically repaired within and after 48 hours of the
      occurrence of fracture and (2) to establish whether timing of repair alone had a
      major role in determining how the patients fared after the surgical repair or
      whether comorbidities also affected outcomes. SAMPLE: The study involved the
      medical records of 49 patients (aged 51 to 99 years) admitted to Coney Island
      Hospital between January 2003 and January 2004 with a primary diagnosis of hip
      fracture who underwent surgical repair. DESIGN: Analysis of data was done by
      retrospective chart review of patients admitted with the diagnosis of hip
      fracture to an acute care hospital setting. Follow-up continued until the
      patients were transferred to a rehabilitation facility for physical or
      occupational therapy after surgery. OUTCOME MEASURES: The preoperative health
      status of each patient was assessed by cardiopulmonary risk index score, based on
      comorbid conditions, and postoperative outcome was determined by complications
      (such as bed sores, pneumonia, urinary tract infection, deep vein thrombosis, or
      pulmonary embolism) or death. RESULTS: Patients who underwent early surgical
      repair (within 48 hours) had fewer postoperative complications (14.7%, as
      compared with 33.3% in the group undergoing surgery >48 hours after fracture).
      CPRI scores in the early and delayed surgery groups were also compared with
      regard to postoperative mortality and morbidity. It appeared that there was a
      higher statistical correlation between CPRI scores and complications among
      patients in the early surgery group (P=0.39) and an insignificant correlation
      among patients in the delayed surgery group (P=0.07). CONCLUSION: Surgical repair
      of hip fractures within the first 48 hours was associated with better health
      outcomes in a nationally representative sample, as observed in an acute care
      facility, irrespective of comorbid conditions.

PMID- 18090876
TI  - Predicting tenofovir concentration on the basis of renal factors determined by
      routine tests.
AB  - Although it has not caused overt renal damage in clinical trials, tenofovir
      disoproxil fumarate (TDF) has been associated with renal dysfunction in isolated
      cases. The objective of this study was to assess the TDF concentration with use
      of the glomerular filtration rate (GFR) and blood urea nitrogen (BUN) level.
      Serum creatinine (used to calculate GFR), BUN, and plasma TDF trough values were
      measured in 51 patient volunteers at pretreatment and post-treatment time points.
      The post-treatment GFR (post_GFR) and the difference between the pretreatment and
      post-treatment BUN levels (dif_BUN) were strongly related to TDF concentration. A
      piecewise multiple regression technique was applied to the nonlinear TDF
      distribution, revealing a significant association of the post_GFR and dif_BUN
      values with TDF concentration (P=0.002 and P= 0.003, respectively). Post_GFR
      values below 125 mL/min/1.73 m(2) and/or dif_BUN values below -3 mg/dL are
      predicted to cause a marked increase in the TDF concentration. The relationship
      between TDF and BUN is a new finding. Knowledge of the pretreatment and post
      treatment serum creatinine and BUN levels is important for the safe clinical
      administration of TDF.

PMID- 18090877
TI  - Effects of enhanced external counterpulsation (EECP) on myocardial perfusion.
AB  - PURPOSE: To evaluate whether enhanced external counterpulsation (EECP) exerts an
      effect on myocardial perfusion. METHODS: Eleven patients with angina were studied
      before and after 35 sessions of EECP treatment. Myocardial perfusion was
      quantified with positron emission tomography and intravenous 13N-ammonia at rest
      and after dipyridamole, by means of a two-compartment mathematical model.
      CONCLUSION: The results suggest that EECP has no effect on myocardial perfusion.
      However, because of the small number of patients in this study and highly
      variable clinical responses, additional studies are required to corroborate this
      finding. The beneficial effects of EECP appear to be mediated by other
      mechanisms.

PMID- 18090878
TI  - Time course of effect of piperazine citrate on the electrocardiogram of the rat.
AB  - The acute electrocardiographic (ECG) changes induced by 4 different doses of
      piperazine citrate (15, 30, 60, and 100 mg/kg) were determined in the
      anesthetized Wistar rat. A dose-dependent reduction in heart rate occurred, from
      9.03%+/-2.97% at a dose of 15 mg/kg to 30.84%+/-3.4% at 100 mg/kg body weight.
      The P-R interval showed dose-dependent increases over values at equilibration,
      increasing from 10.69% +/-2.82% at 15 mg/kg to 24.79%+/-2.71% at 100 mg/kg.
      Similarly, the Q-T interval corrected for heart rate (Q-Tc) showed dose-dependent
      increases, from 4.7%+/-1.89% at 15 mg/kg to 29.40%+/-6.09% at 100 mg/kg. In
      comparison with values for controls, all these changes except those associated
      with 15 mg/kg were statistically significant (P<0.05). Piperazine did not have
      any effect on the duration of the QRS complex except at 100 mg/kg, the dose at
      which marked widening occurred in 3 of the 7 rats. Dysrhythmic phenomena,
      including various forms of atrioventricular (AV) block, sometimes with
      idioventricular rhythms, were also evident in the 3 rats. Severe bradycardia from
      sino-atrial depression and AV block was also observed. At this concentration (100
      mg/kg), 3 of 7 rats died of complete heart block within 30 minutes of drug
      administration. It was concluded that piperazine citrate at the suggested
      antiarrhythmic dose (15 mg/kg intravenously) and even at four times that dose was
      associated with no ECG abnormality suggestive of cardiotoxicity. However, at 100
      mg/kg very serious ECG aberrations can occur, with severe heart block and death.

PMID- 18090879
TI  - Hypertension and cognitive function in the elderly.
AB  - Alzheimer's disease is the most prevalent and common form of cognitive
      impairment, ie, dementia, in the elderly followed in second place by vascular
      dementia due to the microangiopathy associated with poorly-controlled
      hypertension. Besides blood pressure elevation, advancing age is the strongest
      risk factor for dementia. Deterioration of intellectual function and cognitive
      skills that leads to the elderly patient becoming more and more dependent in his,
      her, activities of daily living, ie, bathing, dressing, feeding self, locomotion,
      and personal hygiene. It has been known and demonstrated for many years that
      lowering of blood pressure from a previous hypertensive point can result in
      stroke prevention yet lowering of blood pressure does not prevent the
      microangiopathy that leads to white matter demyelinization which when combined
      with the clinical cognitive deterioration is compatible with a diagnosis of
      vascular dementia. It is known from many large studies, ie, SHEP, SCOPE, and
      HOPE, that lowering of blood pressure gradually will not and should not worsen
      the cognitive impairment. However, if the pressure is uncontrolled a stroke which
      might consequently occur would further worsen their cognitive derangement. So an
      attempt at slow reduction of blood pressure since cerebral autoregulation is
      slower as age increases is in the patient's best interest. It is also important
      to stress that control of blood glucose can also be seen as an attempt to prevent
      vascular dementia from uncontrolled hyperglycemia. Vascular dementia is not
      considered one of the reversible causes of dementia. Reversible causes of
      cognitive impairment are over medication with centrally acting drugs such as
      sedatives, hypnotics, antidepressants, and antipsychotics, electrolyte imbalance
      such as hyponatremia, azotemia, chronic liver disease, and poor controlled
      chronic congestive heart failure. Criteria for the clinical diagnosis of vascular
      dementia include cognitive decline in regards to preceding functionally higher
      level characterized by alterations in memory and in two or more superior cortical
      functions that include orientation, attention, verbal linguistic capacities,
      visual spacial skills, calculation, executive functioning, motor control,
      abstraction and judgment. Patients with disturbances of consciousness, delirium
      (acute confusional states), psychosis, serious aphasia, or sensory-motor
      alterations that preclude proper execution of neuro-psychological testing are
      also considered to have probably vascular dementia. Furthermore, these are ten of
      the other essential cerebral or systematic pathologies present that would be able
      to produce a dementia syndrome.

PMID- 18090880
TI  - Multiple sclerosis and Natalizumab.
AB  - Natalizumab (NTZ), defined as "the first of a new class of drugs known as
      elective adhesion molecule inhibitors" was developed at the beginning of 2003 to
      treat relapsing-remitting multiple sclerosis (MS) and was approved in the United
      States in November 2004. In February 2005, the production of NTZ was suspended by
      Producer Firms on account of the occurrence of two serious adverse events: two
      patients who had been taking NTZ manifested a progressive multifocal
      leukoencephalopathy; the patients showed progressive neurologic deterioration,
      initially believed to be a worsening of the pre-existing condition of MS. In
      March 2006, the Advisory Panel of the Food and Drug Administration voted
      unanimously in favor of the return of NTZ on the market with the majority of the
      panel also recommending that NTZ be considered the first choice of treatment in
      MS. NTZ should only be administered to patients who are not taking other
      medicines for MS and only in highly specialized centers. Inhibiting the adhesion
      of the circulating immune-competent cells to the vascular endothelium and
      reducing the precipitation of the circulating immune complexes (CICs) into the
      central nervous system, NTZ causes the level of the CICs to rise to values that
      inhibit the production of the antibodies (above all of the immunoglobulin Ms);
      because of the relative lack of antibodies, the pertussis toxins, no longer
      complexed, attack the nerve epithelia directly. We must conclude that 1) in
      remittent MS, between one attack and another (successive re-infection of
      bordetella pertussis) there are no CICs that can precipitate into the central
      nervous system, and thus the treatment with NTZ is useless and superfluous; 2) in
      chronic-progressive MS, the final result of the treatment with NTZ will be that
      of transforming MS into lateral amyotrophic sclerosis or progressive multifocal
      leukoencephalopathy; 3) in progressive MS, however, NTZ can be of considerable
      use in the first 2 months of antibiotic treatment to prevent the formation of new
      patches or the re-activation of previous ones. With the halt of toxin production
      (no bordetella pertussis strains resistant to erythrocyne exist) and continuing
      administration of the antibiotic on a long-term basis, there will be no further
      need of NTZ.

PMID- 18090881
TI  - Management of postoperative ileus.
AB  - Postoperative ileus is an abnormal pattern of gastrointestinal motility that is
      common after both abdominal and nonabdominal surgeries. There are many causes of
      ileus, including postoperative pain and the use of narcotics for analgesia,
      electrolyte imbalances, and manipulation of the bowel during surgery. Despite its
      prevalence, there is still no reliable treatment to prevent ileus or shorten its
      course. This article discusses the causes of postoperative ileus and the
      treatment options currently available. The literature on early refeeding, gum
      chewing, and the use of tube feeds is reviewed. In addition, new and experimental
      drugs currently in development are discussed.

PMID- 18090882
TI  - The 'forgotten' bile acid sequestrants: is now a good time to remember?
AB  - Over 30 years ago, bile acid sequestrants (BAS) were among the first drugs
      approved to lower cholesterol levels. For over 10 years, BAS have been known to
      reduce glucose levels. Most importantly, BAS have been shown in outcomes studies
      to reduce cardiovascular events. Because they are true nonsystemic agents, BAS
      are generally safe and not associated with serious systemic adverse experiences.
      Despite their proven atherosclerotic coronary heart disease (CHD) benefits, and
      irrespective of their favorable effects on major CHD risk factors
      (hypercholesterolemia and hyperglycemia), BAS are not among the more frequently
      used drug treatments for hypercholesterolemia, even in patients with type 2
      diabetes mellitus. Recent "high-profile" findings of investigational and approved
      lipid-altering and antidiabetes drug therapies illustrate that drug-induced
      improvements in lipid and glucose levels do not always reduce CHD risk. It may
      therefore be time to reconsider the clinical use of BAS. This review focuses on
      the recent lessons learned, and the potential mechanisms involved in efficacy and
      safety issues raised with torcetrapib and rosiglitazone with analogies related to
      the use of BAS therapy. Known and proposed mechanisms of how BAS may improve
      lipid and glucose levels are discussed, which are effects that may help explain
      how BAS reduce CHD risk. Improved tolerability of newer BAS (eg, colesevelam
      hydrochloride) and a "new" appreciation of the historic benefits of these "old"
      therapeutic agents may lead to an increased treatment role for these drugs,
      particularly in hypercholesterolemic patients with type 2 diabetes mellitus.

PMID- 18090883
TI  - Is acetazolamide similar to topiramate for reversal of antipsychotic-induced
      weight gain?
AB  - Acetazolamide (AZD), a sulfa-like moiety, is a potent, nonspecific inhibitor of
      carbonic anhydrase (CA) enzymes and has been demonstrated to decrease lipogenesis
      in adipose cells in in vitro cell culture studies. In contrast, topiramate (a
      sulfamate moiety) appears to inhibit specific (CA) enzymes II and V. Four placebo
      controlled trials with topiramate have demonstrated positive results in weight
      loss. There is only anecdotal evidence that AZD may cause weight loss. The
      following case is of a 49-year-old African-American woman with a long history of
      schizoaffective disorder, hypertension, diabetes type II, stress incontinence,
      and obesity (body mass index, 45.5 kg/m2). Previous trials of topiramate
      demonstrated temporary but significant weight loss before AZD use. A 4 week
      washout period occurred before starting AZD, 250 mg twice daily. Significant
      weight loss of 11.5 lbs was seen over 4 weeks. During washout periods of either
      topiramate or AZD, her total mean weight was approximately 2 to 7 lbs higher than
      when she was treated with AZD. Although tolerance and side effects may limit the
      use of AZD as a safe and effective strategy for medication-related weight gain,
      the pharmacology may provide research insights into the causes and treatments of
      obesity.

PMID- 18090884
TI  - Dapsone-induced methemoglobinemia: case report and literature review.
AB  - Dapsone is a potent cause for introgenic methemoglobinemia that is frequently
      unrecognized. We describe such a case with successful antidotal therapy.

PMID- 18090885
TI  - Emphysematous pyelonephritis presenting as gastroenteritis.
AB  - Emphysematous pyelonephritis (EPN) is a serious and often life-threatening
      condition due to a gas-producing and necrotizing infection involving the renal
      parenchyma and perirenal tissue. The infection is almost exclusively seen in
      diabetic patients, and the main feature of its presence is finding gas within the
      kidney. Patients usually present with fever, chills, flank pain, and dysuria.
      Laboratory testing usually reveals hyperglycemia, leukocytosis, pyuria, an
      elevated blood urea nitrogen (BUN) level, and high serum creatinine level. Other,
      nonspecific symptoms such as abdominal pain, nausea, vomiting, and diarrhea can
      accompany acute pyelonephritis, as found in the reported case. The appropriate
      management of such serious infection requires combined medical and surgical
      treatment. In severe infection, nephrectomy should not be delayed. We report a
      case of EPN in a diabetic patient who presented with gastrointestinal symptoms. A
      high index of suspicion, coupled with a good imaging study [preferably computed
      tomography (CT) scanning] of the abdomen can lead to early diagnosis. Appropriate
      medical and surgical management have resulted in a successful outcome.

PMID- 18090888
TI  - Aspheric intraocular lens selection: the evolution of refractive cataract
      surgery.

PMID- 18090886
TI  - First-in-Man (FIM) clinical trials post-TeGenero: a review of the impact of the
      TeGenero trial on the design, conduct, and ethics of FIM trials.
AB  - A recent first time in man (FIM) trial of an "immuno modulator" compound
      (TGN1412) resulted in unprecedented toxicity. Since this occurred in 2006 a
      widely publicized scientific debate, as well as a controversy in the lay
      community has examined the principle of design and content of the study as well
      as the concept of FIM studies. This paper reviews the controversy, analyzes the
      problems of the TGN1412 trial and FIM trials in general and the reaction of the
      lay and scientific communities. Difficulties in these high risk trials is
      highlighted and possible design and execution procedural improvements are
      recommended. Consideration is given to the ethical debate regarding participation
      of normal, healthy research volunteers in FIM studies. The role of monetary
      incentive(s) is discussed as well as the opposition of many participants in this
      debate on financial compensation of volunteers for the assumption of risk and the
      need to adopt a no-fault scheme that fairly compensates injured trial
      participants.FIM studies are critical for the development of new therapeutic
      agents. Improving trial design and execution and fairly compensating volunteers
      will facilitate these studies, enhance equity and thus provide an ethical basis
      for continuing FIM studies that may pose a serious risk to participants, a risk
      that society needs taken for the development of needed therapeutic agents.

PMID- 18090889
TI  - Patient-centered care and refractive cataract surgery.
AB  - PURPOSE OF REVIEW: Cataract surgery has evolved significantly during the last few
      years. The introduction of aspheric, presbyopic correcting and toric intraocular
      lenses have shifted the emphasis of cataract surgery from just treating patients'
      functional symptoms to optimizing the refractive outcome of the procedure. RECENT
      FINDINGS: Studies emphasizing patient satisfaction and refractive visual outcomes
      have shifted the focus of cataract surgery to a more patient-centered approach.
      Refractive surgical technologies such as limbal relaxing incisions, laser
      assisted in-situ keratomileusis, photorefractive keratectomy and conductive
      keratoplasty can be used in conjunction with traditional cataract surgical
      techniques. The wide array of intraocular lens choices has broadened the scope of
      refractive cataract surgery providing surgeons and patients with more options in
      determining refractive outcomes. SUMMARY: Cataract surgery has expanded into the
      realm of refractive surgery and there is a new emphasis on patient-centered care
      and an optimization of the refractive outcome of the procedure. This trend will
      continue as newer presbyopic correcting intraocular lenses become available.

PMID- 18090890
TI  - Neuroadaptation of presbyopia-correcting intraocular lenses.
AB  - PURPOSE OF REVIEW: Advances in the design of intraocular lenses give options to
      patients for some return to the optical accommodation needed to focus on objects
      at different distances. Technology is only improving these options for presbyopic
      correcting intraocular lenses. Surgeons must consider the possible
      neuroadaptation abilities in patients that may help in the success of using these
      lenses. RECENT FINDINGS: The hierarchy of the visual system allows two disparate
      retinal images to combine to form a single picture with depth. Attempts to
      correct presbyopia with intraocular lenses add complexity to the pathway with the
      possible introduction of monovision or intraocular rivalry. The neuroadaptation
      involved in successful use of these lenses has not been study but has been well
      established in other neurologic processing. SUMMARY: Understanding what patient
      selection factors are important for neuroadaptation may contribute to outcome
      success.

PMID- 18090891
TI  - Biometry and intraocular lens power calculation.
AB  - PURPOSE OF REVIEW: Heightened patient expectations for precise postoperative
      refractive results have spurred the continued improvements in biometry and
      intraocular lens calculations. In order to meet these expectations, attention to
      proper patient selection, accurate keratometry and biometry, and appropriate
      intraocular lens power formula selection with optimized lens constants are
      required. The article reviews recent studies and advances in the field of
      biometry and intraocular lens power calculations. RECENT FINDINGS: Several
      noncontact optical-based devices compare favorably, if not superiorly, to older
      ultrasonic biometric and keratometric techniques. With additional improvements in
      the internal acquisition algorithm, the new IOL Master software version 5 upgrade
      should lessen operator variability and further enhance signal acquisition. The
      modern Haigis-L and Holladay 2 formulas more accurately determine the position
      and the shape of the intraocular lens power prediction curve. SUMMARY:
      Postoperative refractive results depend on the precision of multiple factors and
      measurements. The element with the highest variability and inaccuracy is,
      ultimately, going to determine the outcome. By understanding the advantages and
      limitations of the current technology, it is possible to consistently achieve
      highly accurate results.

PMID- 18090892
TI  - Refractive enhancement following presbyopia-correcting intraocular lens
      implantation.
AB  - PURPOSE OF REVIEW: Presbyopia-correcting intraocular lenses are widely available.
      Residual ametropia is one of the most common issues that can result in patient
      dissatisfaction. Options for correcting refractive surprises include piggyback
      intraocular lens implantation, corneal incisional surgery and laser correction.
      Excimer laser surgery is a safe and predictable method to correct residual
      amounts of ametropia in pseudophakic patients with monofocal intraocular lenses;
      however, there is scant published literature regarding this technique. RECENT
      FINDINGS: Presbyopia-correcting intraocular lenses require emmetropia for the
      best visual outcome, as small amounts of astigmatism or residual refractive
      errors can limit their visual performance. Laser-assisted in-situ keratomileusis
      and photorefractive keratectomy are safe and effective results in pseudophakic
      patients. Surgeons can refine the refractive outcome after intraocular lens
      implantation with the excimer laser to achieve better results and higher patient
      satisfaction. SUMMARY: Excimer laser corneal surgery for fine-tuning residual
      ametropia after presbyopia-correcting intraocular lenses is a safe adjunct
      treatment to increase patient satisfaction. Which technique (photorefractive
      keratectomy or laser-assisted in-situ keratomileusis) to use depends on surgeon
      preference and patient characteristics, as both demonstrate similar results in
      published literature. Knowledge of all available refractive methods and
      technologies are crucial for improving outcomes in these patients.

PMID- 18090893
TI  - Perioperative antibiotics and anti-inflammatory agents in cataract surgery.
AB  - PURPOSE OF REVIEW: Cataract surgery has benefited from great technical advances
      but no consensus exists as regards optimal perioperative medical management of
      inflammation and infection prophylaxis. RECENT FINDINGS: The present article
      primarily reviews recent evidence about the most advantageous antibiotic regimen
      to minimize endophthalmitis, and the utility of steroids or nonsteroidal anti
      inflammatory drugs (NSAIDs) in management of both postoperative inflammation and
      cystoid macular edema. Prospective data from Europe supports the efficacy of
      intracameral cephalosporins in reducing the incidence of endophthalmitis. We
      compare this with retrospective data from the United States describing a low
      incidence of endophthalmitis when using fourth-generation fluoroquinolones as
      chemoprophylaxis. Other studies demonstrate the anti-inflammatory effect of
      multiple perioperative topical NSAIDs. Further important questions remain,
      however, including whether NSAIDs exhibit a superior side-effect profile relative
      to corticosteroids, whether benefit exists to combination NSAID/corticosteroid
      therapy, as well as whether NSAIDS can reduce the incidence of cystoid macular
      edema. SUMMARY: New evidence clarifies the use of intracameral antibiotics, and
      other studies support a niche anti-inflammatory role for NSAIDs.

PMID- 18090894
TI  - Pathophysiology of zonular diseases.
AB  - PURPOSE OF REVIEW: The mechanisms implicated in the clinical manifestations of
      zonular diseases, especially ectopia lentis, are reviewed. RECENT FINDINGS: The
      molecular mechanisms involve fibrillin in a large spectrum of heritable diseases
      characterized by zonular stretching. The usual complications are refractive
      errors, especially myopia, glaucoma (either primary open angle, secondary angle
      closure and pupil block by anterior displacement of the lens) and retinal
      detachment. SUMMARY: The genetics and molecular understanding provide information
      for genetic counseling. Treatment of myopia and glaucoma depend on the underlying
      mechanism, and lens surgery techniques are continuously improved.

PMID- 18090895
TI  - Surgical strategies for the management of zonular compromise.
AB  - PURPOSE OF REVIEW: To evaluate new surgical treatment of zonular instability
      during cataract surgery. RECENT FINDINGS: The increased risk of complications
      associated with zonular compromise during cataract surgery has led to development
      of the capsular tension ring. More recently, the modified capsular tension ring
      and capsular tension segment have been introduced, allowing improved capsular
      stability and intraocular lens centration by scleral-suture fixation. Capsule
      support hooks also have a role in capsular stabilization. SUMMARY: When faced
      with zonular instability, the increased availability and use of capsular support
      devices allow for improved safety and outcome in cataract surgery.

PMID- 18090896
TI  - Managing the broken capsule.
AB  - PURPOSE OF REVIEW: Posterior capsular rupture is a common complication of
      cataract extraction surgery. Prompt management of anterior and posterior capsular
      tears may prevent associated complications or need for subsequent procedural
      intervention. RECENT FINDINGS: When tears develop in the anterior capsule, novel
      techniques allow predictable rescue of a capsulorhexis, preventing radial
      extension to the posterior capsule. Several case series now describe techniques
      and outcomes of posterior assisted levitation techniques for a dislocated
      nucleus. Triamcinolone staining of the vitreous improves visualization and
      removal of vitreous in the anterior segment following capsular rupture. Recently
      published studies further describe the increased risks of endophthalmitis and
      retinal detachment following capsular tears. SUMMARY: Several techniques may
      prove beneficial in the intraoperative management of an anterior capsular tear, a
      dislocated nucleus, or vitreous loss.

PMID- 18090897
TI  - Biocompatibility of intraocular lens materials.
AB  - PURPOSE OF REVIEW: To provide an update on currently available materials used in
      the manufacture of intraocular lenses, as well as new materials under
      development, especially with regard to their uveal and capsular biocompatibility.
      RECENT FINDINGS: The biocompatibility of intraocular lens materials should be
      assessed in terms of uveal biocompatibility, related to the inflammatory foreign
      body reaction of the eye against the implant, as well as in terms of capsular
      biocompatibility, determined by the relationship of the intraocular lens with
      remaining lens epithelial cells within the capsular bag. This situation may
      result in different entities, e.g. anterior capsule opacification,
      interlenticular opacification (between piggyback intraocular lenses), posterior
      capsule opacification and lens epithelial cell ongrowth. Reports on intraocular
      lens opacification suggest that the potential to calcify should also be taken
      into consideration when evaluating the long-term biocompatibility of a new
      material. SUMMARY: Intraocular lenses are being progressively implanted in much
      earlier stages of life (refractive lens exchange, pediatric implantation) and are
      expected to remain in the intraocular environment for many decades. Materials
      used in intraocular lens manufacture should, therefore, insure long-term uveal
      and capsular biocompatibility, as well as ultimate transparency after
      implantation.

PMID- 18090898
TI  - Ophthalmic viscosurgical devices.
AB  - PURPOSE OF REVIEW: The indications for ophthalmic viscosurgical devices have
      expanded with the introduction of newly developed ophthalmic viscosurgical
      devices. The characteristics of different ophthalmic viscosurgical devices and
      their specific uses in anterior segment surgery and possible problems are
      discussed. RECENT FINDINGS: Ophthalmic viscosurgical devices were first
      introduced to maintain space in the eye during the implantation of intraocular
      lenses. With the development of different types of ophthalmic viscosurgical
      devices, additional indications have been discussed. To protect the corneal
      endothelium, the ability of ophthalmic viscosurgical devices to be retained
      during phacoemulsification was compared. To enlarge and stabilize the size of the
      pupil, specific ophthalmic viscosurgical devices are used in patients with small
      pupils or intraoperative floppy iris syndrome. On the other hand, complications
      associated with the use of ophthalmic viscosurgical devices and their prevention
      have been discussed. Postoperative elevations of intraocular pressure have been
      reported and complete removal of the ophthalmic viscosurgical device at the end
      of surgery is the key factor to avoiding these elevations. Wound burns during
      phacoemulsification may occur and creating a fluid space around the
      phacoemulsification tip is necessary to avoid them. SUMMARY: The rheologic
      characteristics of the different types of ophthalmic viscosurgical device should
      be considered, and the appropriate use of ophthalmic viscosurgical devices in
      specific cases would improve the surgical outcomes.

PMID- 18090899
TI  - Cataract surgery for the developing world.
AB  - PURPOSE OF REVIEW: To review surveys published within the last year concerning
      the prevalence of cataract blindness, rates of cataract surgical coverage and
      visual outcomes of cataract surgery in various developing countries, and to
      review recent studies that compare the different cataract surgical techniques
      used in developing countries. RECENT FINDINGS: Up to 75% of blindness (visual
      acuity below 20/400) is due to cataract. Cataract remains the most common
      treatable cause of blindness. Reported cataract surgical coverage is low, and
      visual outcomes are poor and necessitate improvement. Phacoemulsification is the
      preferred technique for cataract surgery in developed countries, but large-scale
      implementation in developing countries may prove to be a challenge. An
      alternative surgical technique, manual sutureless small incision extracapsular
      cataract surgery, has been increasing in popularity, as the technique has been
      shown to yield similar surgical outcomes as phacoemulsification. SUMMARY:
      Treating cataract blindness worldwide continues to be a formidable challenge.
      Significant barriers include cost, lack of population awareness, shortage of
      trained personnel and poor surgical outcomes. Both phacoemulsification and manual
      small incision extracapsular cataract surgery achieve excellent visual outcomes
      with low complication rates, but manual small incision extracapsular cataract
      surgery is significantly faster, less expensive and requires less technology.
      Therefore, manual small incision extracapsular cataract surgery may be the
      preferred technique for cataract surgery in the developing world.

PMID- 18090900
TI  - Cataract surgery and intraocular lens manufacturing in India.
AB  - PURPOSE OF REVIEW: Cataract surgery in India has seen exponential growth in the
      past decade. This leap was possible due to cost-effective cataract surgery with
      intraocular lenses. The purpose of this review is to update the reader regarding
      the Indian scenario of cataract surgery and intraocular lens manufacturing.
      RECENT FINDINGS: India performed an estimated 0.5 million cataract surgeries in
      1981-1982; this increased to 4.8 million in 2006 with 90% intraocular lens
      acceptance. There has been a sustained shift from sutured extracapsular cataract
      surgery to small-incision cataract surgery. Phacoemulsification with foldable
      lenses is becoming the surgical choice in the urban setting. The Indian
      intraocular lens industry is maturing from a low-cost manufacturer to a quality
      conscious, technology-driven and value-priced industry to meet present and future
      market needs. SUMMARY: The burden of cataract blindness is a major challenge for
      all developing countries. India has managed to improve its cataract surgical rate
      by an amalgam of factors such as low surgical costs, low-cost indigenous eye-care
      consumables, infrastructure development and enhanced training. The findings from
      this review will be useful to develop strategies to enhance the uptake of
      cataract surgery in developing countries.

PMID- 18090901
TI  - Nutrition and the prevention of cataracts.
AB  - PURPOSE OF REVIEW: Oxidative stress is a major cause of cataract development.
      Numerous studies have been published regarding the effects of nutritional
      supplementation on cataract progression. RECENT FINDINGS: Basic science research
      has demonstrated a protective effect of antioxidants on lens tissue, and
      supplementation with vitamin C and lutein/zeaxanthin has been associated with a
      decreased risk of cataract formation in multiple observational studies. One large
      interventional trial demonstrated a significant difference in participants
      treated with high-dose vitamin C versus placebo, but a more recent interventional
      study did not replicate these findings. In a review of the carotenoids lutein and
      zeaxanthin, the Food and Drug Administration concluded there is insufficient
      evidence to suggest that supplementation with these carotenoids lowers the risk
      of cataract formation. While high doses of multivitamins, antioxidants, or lutein
      and zeaxanthin are unlikely to be of significant ophthalmic benefit to the
      general public, these nutrients may help individuals exposed to high oxidative
      stress, such as heavy smokers, and those with poor nutrition. SUMMARY:
      Supplementation with vitamin C, lutein, zeaxanthin, or a multivitamin may help
      certain populations, but is unlikely to affect the progression of cataracts in
      most patients.

PMID- 18090902
TI  - Bibliography. Current world literature. Cataract surgery and lens implantation.

PMID- 18090903
TI  - Secular trends in cancer mortality among Japanese immigrants in the state of Sao
      Paulo, Brazil, 1979-2001.
AB  - We investigated secular trends in cancer mortality among first-generation
      Japanese-Brazilians in the state of Sao Paulo between 1979 and 2001. Results were
      compared with those for Japanese living in Japan and Brazilians living in the
      state of Sao Paulo. We used mortality data for three periods, 1979-1981, 1989
      1991, and 1999-2001, and population data from Brazilian censuses in 1980, 1991,
      and 2000 for Japanese-Brazilians. Available mortality and population data for
      Japanese living in Japan and Brazilians living in the state of Sao Paulo
      corresponding to those for Japanese-Brazilians were obtained. Age-standardized
      mortality rates for Japanese-Brazilians and standardized mortality ratios based
      on mortality of Japanese living in Japan in 1980 for the three different periods
      and populations were calculated. We observed a decreasing trend for stomach
      cancer and increasing trends for colon, breast and prostate cancer over the 20
      years in all three populations. Standardized mortality ratios for stomach cancer
      in Japanese-Brazilians declined to approximately those of Japanese living in
      Japan. Although standardized mortality ratios from colon, breast and prostate
      cancer in Japanese-Brazilians increased over the last 20 years, those for colon
      cancer were similar to the Japanese living in Japan whereas those for breast and
      prostate cancer (208 and 423 in 2000, respectively) appeared to be intermediate
      between those for Japanese living in Japan (152 and 208 in 2000, respectively)
      and Brazilians living in the state of Sao Paulo (281 and 536 in 2000,
      respectively). Standardized mortality ratios for liver and lung cancer increased
      in Japanese living in Japan over the last 20 years but no increasing trend was
      observed for Japanese-Brazilians, except for liver cancer in men, and
      standardized mortality ratios in Japanese-Brazilians seemed to be similar to the
      Brazilians living in the state of Sao Paulo. Secular trends in mortality confirm
      the relative importance of environment in the development of cancer.

PMID- 18090904
TI  - Electrophoretic pattern of proteins in carcinoma of the gallbladder.
AB  - Carcinoma of the gallbladder is a common health problem in the northern region of
      India and in spite of improved diagnostic techniques it is generally diagnosed at
      an advanced stage. This study was carried out in 60 patients, 30 of whom were
      diagnosed with gallbladder carcinoma and 30 with cholelithiasis. The protein
      content in tissue extracts and serum was determined using the Folin method of
      Lowry. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis was performed
      for the identification of proteins according to Laemmli. The results showed the
      mean concentration of total protein in gallbladder tissue of patients with
      carcinoma of the gallbladder was 51.83 +/- 3.36 mg/g tissue (45.33-57.80) and in
      patients with cholelithiasis it was 38.82 +/- 9.11 mg/g tissue (29.55-50.99)
      (P<0.001). Protein electrophoresis of gallbladder tissue from the patients with
      carcinoma of the gallbladder showed three additional bands of protein (two
      protein bands were present in the region of 50-55 kDa and the third band was
      present in the region of 35 kDa), which were absent in the gallbladder tissue of
      cholelithiasis patients. Mean total protein content in serum was 72.2 +/- 1.73
      g/l (67.98-74.99) in patients of carcinoma of the gallbladder, whereas it was
      71.01 +/- 3.4 g/l (60.00-78.99) (P>0.05) in the patients with cholelithiasis.
      Electrophoretic analysis of serum protein revealed at least two additional
      protein bands in patients with carcinoma of the gallbladder as compared with
      electrophoretic pattern in cholelithiasis. These two bands were in the range of
      80 and 25 kDa proteins. In conclusion, the presence of these new bands of protein
      in the gallbladder tissue and serum of the patients with carcinoma of the
      gallbladder indicate their role in the pathogenesis of the carcinoma of the
      gallbladder.

PMID- 18090905
TI  - Trends in incidence of digestive cancers in France.
AB  - The objective of this study was to analyse trends in the incidence of digestive
      cancers in France. Observed incidence and mortality data in the population
      covered by cancer registries were modelled using age-cohort models. An estimation
      of the incidence/mortality ratio was obtained from these models and was applied
      to the mortality rates predicted from an age-cohort model for the entire French
      population. Site-specific standardized-incidence rates by 1-year intervals and
      cumulative rate 0-74 years by birth cohort were estimated. On average, age
      standardized incidence rates of large bowel cancers increased by 1.0% per year in
      men and 0.8% in women from 1980 to 2000. The estimated cumulative rate increased
      from 4.0% for men born in 1913 to 4.8% for those born in 1953. The corresponding
      values in women were 2.5 and 2.9%. The most striking increase in incidence was
      seen for primary liver cancer with an increase from 2000 incident cases in 1980
      to nearly 6000 in 2000. The estimated cumulative rate was 0.5% for men born in
      1913 and 2.9% for those born in 1953. The increase in incidence was lower for
      pancreas cancer. A decrease in the incidence of stomach cancer was observed for
      both sexes and of oesophageal cancer in men by slightly more than 2%. The study
      showed large changes in the cancer burden in France between 1980 and 2000.

PMID- 18090906
TI  - Patterns and trends of pancreatic cancer mortality rates in Arkansas, 1969-2002:
      a comparison with the US population.
AB  - Little is known about trends in pancreatic cancer mortality in individual states
      of the US and its whole population. This study aimed to describe the patterns and
      trends of pancreatic cancer mortality in Arkansas, 1969-2002, using the US
      national rates as a reference. Joinpoint regression analyses were performed to
      evaluate trends in age-standardized mortality rates of pancreatic cancer by age
      group, sex, and race, using data obtained from the National Center for Health
      Statistics. Throughout the period examined, mortality decreased in young and
      middle-aged people (<60 years) and men but increased in old people (>/=60 years)
      and women. A continuous fall in mortality occurred among whites except for a
      transient rise in the late 1970s. For blacks, mortality rates did not cease to
      increase until 1995. Unlike in Arkansas, a monotonic upward or downward trend in
      mortality by age group and sex was not observed in the US. A decline of mortality
      stopped in 1997 for US whites. Recent decreasing trends were more pronounced in
      Arkansas blacks than in US blacks. Changes of pancreatic cancer mortality in the
      last three decades in Arkansas remarkably differed by age, sex, and race and were
      different in patterns from those of the US population.

PMID- 18090907
TI  - The interleukin-8-251*T/*A polymorphism is not associated with risk for gastric
      carcinoma development in a Portuguese population.
AB  - It has been demonstrated that polymorphisms within inflammation-related genes are
      associated with risk of gastric carcinoma in Helicobacter pylori-infected
      individuals. Recently, several studies have reported conflicting results
      regarding the association between the interleukin (IL)8-251*T/*A polymorphism and
      risk of gastric carcinoma. In this study, we performed a case-control analysis,
      including 693 controls, 187 chronic gastritis cases and 333 gastric carcinoma
      cases, to determine the association between the IL8-251 polymorphism and risk of
      chronic gastritis and gastric carcinoma in the northern Portugal population. We
      found no significant association between the IL8-251 polymorphism and increased
      risk of chronic gastritis or gastric carcinoma, in agreement with that reported
      in other populations of white origin. The retrospective analysis of published
      data shows that the association between the IL8-251 polymorphism and risk of
      gastric carcinoma tends to be reproducible in populations of Asian origin. The
      estimated effect of the polymorphism under analysis was not significantly
      different in subgroups of gastric carcinoma cases defined by histologic type and
      anatomic site of the tumours, and by sex and age of the participants. In
      conclusion our results indicate that although the IL8-251 polymorphism might be a
      relevant host susceptibility factor for gastric carcinoma development, this
      association is likely to be ethnic-specific.

PMID- 18090908
TI  - Human epithelial growth factor receptor 2[Ile655Val] polymorphism and risk of
      breast fibroadenoma.
AB  - Studies on the association between the Ile to Val polymorphism at codon 655 of
      the human epithelial growth factor receptor 2 (HER-2) gene and susceptibility to
      breast cancer have been reported for almost all ethnic populations, with both
      positive or negative conclusions. No study, however, has yet been focused on the
      possible association between this gene and its predisposition to benign breast
      lesions, especially on risk for fibroadenoma. We aimed to study the association
      of the single nucleotide polymorphism V655 HER-2 gene polymorphism with
      histologically verified breast fibroadenoma risk. We conducted a molecular
      epidemiological case-control study of 70 breast fibroadenoma cases without
      cellular atypia and 172 healthy female controls. We found that the Val variant
      allele and genotype frequency of this polymorphism is higher in cases with
      fibroadenoma; however, this difference was not significant (allele Val 655: 27.86
      and 22.67% in fibroadenoma and controls, respectively; genotype Ile/Val: 35.71
      and 38.37% and Val/Val: 10.0 and 3.49% in fibroadenoma and controls,
      respectively). Applying logistic regression analysis, we found an increased risk
      of fibroadenoma formation in carriers of the Val allele (odds ratio = 1.17; 95%
      confidence interval = 0.67-2.05), in which the highest risk was associated with
      homozygous genotype (odds ratio = 3.07; 95% confidence interval = 0.97-9.72), but
      this risk was not significant. Stratification by age (cut-off 45 years) revealed
      the highest risk of fibroadenoma among young women homozygous for the Val allele
      (odds ratio = 3.30). The risk, however, was slightly increased (odds ratio =
      1.24) among older carriers of the aberrant allele in their genotype as well, but
      it was not significant. In spite of insignificant differences, our results
      indicate that HER-2 Ile655Val polymorphism, especially in a homozygous form might
      play some role in the etiology of breast fibroadenoma formation. The significance
      of this susceptibility, however, will have to be verified by larger studies.

PMID- 18090909
TI  - Meat consumption, N-acetyl transferase 1 and 2 polymorphism and risk of breast
      cancer in Danish postmenopausal women.
AB  - The aim of this study was to investigate whether polymorphisms in N-acetyl
      transferase 1 and 2 modify the association between meat consumption and risk of
      breast cancer. A nested case-control study was conducted among 24 697
      postmenopausal women included in the 'Diet, Cancer and Health' cohort study (1993
      2000). Three hundred and seventy-eight breast cancer cases were identified and
      matched to 378 controls. The incidence rate ratio (95% confidence interval) for
      breast cancer was 1.09 (1.02-1.17) for total meat, 1.15 (1.01-1.31) for red meat
      and 1.23 (1.04-1.45) for processed meat per 25 g daily increment in intake.
      Compared with slow acetylators, the IRR (95% confidence interval) among fast N
      acetyl transferase 1 acetylators was 1.43 (1.03-1.99) and 1.13 (0.83-1.54) among
      intermediate/fast N-acetyl transferase 2 acetylators. Interaction analyses
      revealed that the positive associations between total meat intake and red meat
      intake and breast cancer risk were confined to intermediate/fast N-acetyl
      transferase 2 acetylators (Pinteraction = 0.03 and 0.04). Our findings support an
      association between meat consumption and breast cancer risk and that N-acetyl
      transferase 2 polymorphism has a modifying effect on the association, indicating
      that the association is confined to only genetically susceptible women.

PMID- 18090910
TI  - Influence of physician and patient characteristics on adherence to breast cancer
      screening recommendations.
AB  - Identifying physician and patient characteristics is important in implementing
      effective, targeted strategies to improve breast cancer detection rates through
      increased screening recommendations and uptake. The purpose of this study was to
      determine whether Ontario physicians recommend breast screening using mammography
      every 2 years for women aged 50-69 as encouraged by the Ontario Breast Screening
      Program. This study also aimed to identify physician and patient characteristics
      that may influence adherence to these recommendations. The study design was a
      cross-sectional study. Using the Canadian Medical Directory-Ontario database,
      3063 questionnaires were mailed to all active general and family practitioners. A
      response rate of 38% (N = 939) was achieved. Adherence to screening was defined
      as recommending screening to women aged 50-69 only, every 2 years as outlined by
      the Ontario Breast Screening Program. Bivariate analyses and unconditional
      logistic regression were used to assess physician adherence to screening
      guidelines. Only 38.9% of physicians followed recommended breast screening
      guidelines. After adjusting for physician sex and age, predictors of screening
      adherence include physicians working in academic or research centers (odds ratio
      8.3, 95% confidence interval 1.7-39.7) and those reporting that over 31% of their
      patients to be of low-income (odds ratio 1.6, 95% confidence interval 1.1-2.4).
      Compared with physicians working in a rural/town setting (<10 000 people), those
      located in a large city (>100 000 people) were less likely to adhere to screening
      guidelines (odds ratio 0.5, 95% confidence interval 0.3-0.7). A low proportion of
      Ontario physicians adhere to recommended breast screening guidelines. Future
      research into effective strategies to increase adherence should take into account
      practice location, setting and patient characteristics.

PMID- 18090911
TI  - Protective effect of Acticoa powder, a cocoa polyphenolic extract, on prostate
      carcinogenesis in Wistar-Unilever rats.
AB  - The effects of Acticoa powder on prostate carcinogenesis were investigated using
      the N-methylnitrosourea and testosterone propionate prostate tumor model. Sixty
      male Wistar-Unilever rats were randomly divided in four groups of 15 rats: one
      control group not induced but treated with vehicle (not induced+vehicle) and
      three chemo-induced groups. Two weeks before prostate tumor induction and then
      throughout the experiment, chemo-induced rats were orally treated with Acticoa
      powder at 24 (chemo-induced+Acticoa powder24) or 48 (chemo-induced+Acticoa
      powder48) mg/kg or with vehicle (chemo-induced+vehicle), daily from Monday to
      Friday. Survival, body weight, food and water consumption were recorded
      throughout the experiment. Six rats per group were randomly killed 9 months after
      the prostate tumor induction for histopathological analysis of prostates. A
      reduction in the incidence of prostate tumors was observed for the chemo
      induced+Acticoa powder48-treated group in comparison with the chemo
      induced+vehicle-treated group and no tumors were observed in the chemo
      induced+Acticoa powder24-treated group as in the not induced+vehicle-treated
      group after 9 months. The nine remaining rats per group were maintained in a long
      term survival study. The life span of the chemo-induced+Acticoa powder24-treated
      group was significantly increased in comparison with the chemo-induced+Acticoa
      powder48 and the chemo-induced+vehicle-treated groups, close to the one of the
      not induced+vehicle-treated group. A significant reduction in the incidence of
      prostate tumors was also observed for the chemo-induced+Acticoa powder24 and
      chemo-induced+Acticoa powder48-treated groups in comparison with the chemo
      induced+vehicle-treated group. In conclusion, Acticoa powder at 24 mg/kg
      protected rats from prostate carcinogenesis when chronically given before the
      initiation and promotion phases of induction.

PMID- 18090912
TI  - BRCA1 mutations and prostate cancer in Poland.
AB  - Evidence to date that BRCA1 mutation carriers are at an increased risk of
      prostate cancer is mixed - both positive and negative studies have been
      published. To establish whether or not inherited variation in BRCA1 influences
      prostate cancer risk we genotyped 1793 men with prostate cancer in Poland and
      4570 controls for three founder mutations (C61G, 4153delA and 5382insC). A BRCA1
      mutation was present in 0.45% of the cases and 0.48% of the controls (odds
      ratio=0.9; P=1.0). The odds ratios varied substantially by mutation. The 5382insC
      mutation is the most common of the three founder mutations. It was detected only
      in one case (0.06%), whereas it was seen in 0.37% of controls (P=0.06). In
      contrast, the 4153delA was more common in prostate cancer cases (0.22%) than in
      controls (0.04%) (odds ratio=5.1; 95% confidence interval: 0.9-27.9; P=0.1). The
      C61G mutation was also found in excess in cases (0.17%) compared with controls
      (0.07%) (odds ratio=2.6; 95% confidence interval: 0.5-12.7; P=0.5). Eight men
      with prostate cancer carried a mutation. Only one of these carried the 5382insC
      mutation, compared with 17 of 22 individuals with mutations in the control
      population (P=0.003). These data suggest that the 5382insC mutation is unlikely
      to be pathogenic for prostate cancer in the Polish population. The presence of
      one of the other alleles was associated with an increased risk for prostate
      cancer (odds ratio=3.6; 95% confidence interval: 1.1-11.3; P=0.045); in
      particular for familial prostate cancer (odds ratio=12; 95% confidence interval:
      2.9-51; P=0.0004). We consider that the risk of prostate cancer in BRCA1 carriers
      varies with the position of the mutation.

PMID- 18090913
TI  - The relation of soy intake and isoflavone levels in nipple aspirate fluid.
AB  - Given the possible breast cancer preventive effects of isoflavones, substances
      with an estrogen-like structure occurring in soybeans, it is of interest to
      assess levels directly in the breast. The objective of this pilot study was to
      measure isoflavones in nipple aspirate fluid. In a pilot study with 11 women,
      nipple aspirate fluid and urine samples were collected at baseline and after 1
      month of consuming two servings of soymilk per day. In a parallel investigation,
      one woman donated nipple aspirate fluid, blood, and urine on the same day after
      consuming different amounts of soy for 9 days. Nipple aspirate fluid was
      collected with an aspirator, diluted 1 : 11, and stored at -20 degrees C.
      Isoflavonoids in nipple aspirate fluid, serum, and urine were liquid-liquid
      extracted after enzymatic hydrolysis followed by liquid chromatography
      electrospray ionization high resolution tandem mass spectrometry analysis using
      triply C labeled internal isoflavonoid standards. After the 30-day soy
      intervention, median nipple aspirate fluid yield changed very little (P=0.47),
      whereas urinary isoflavonoid excretion (P=0.04) and isoflavonoid levels in nipple
      aspirate fluid (P=0.12) increased substantially. For the nine samples collected
      in one participant, isoflavonoids measured in nipple aspirate fluid, plasma, and
      urine were highly correlated with the number of daily soy servings and with each
      other. This pilot study indicates that isoflavonoids in nipple aspirate fluid are
      10 times lower than in plasma and are closely related to levels of isoflavonoids
      in urine and plasma. These findings show that isoflavonoids are present in breast
      fluid and may act directly on breast tissue.

PMID- 18090914
TI  - Neuropathology--for the living and the future.

PMID- 18090915
TI  - Assessment of epidermal nerve fibers: a new diagnostic and predictive tool for
      peripheral neuropathies.
AB  - Today, skin biopsies can play an important role in the diagnosis of peripheral
      nerve disorders and have yielded another diagnostic tool for the neurologist. One
      of the commonly reported neuropathologic abnormalities observed in skin biopsies
      is a reduction of epidermal nerve density. Analyzing the changes in the
      morphology and density of epidermal nerves is of immense diagnostic and
      prognostic value in peripheral neuropathies. These changes also provide an
      assessment of disease progression and of tissue responses to regenerative
      treatments. Combined with immunohistochemical studies, newly evolved skin biopsy
      and epidermal count techniques have the potential to provide significant
      information about the pathogenesis of many peripheral nervous system diseases.
      They have great potential for impacts on both research and clinical approaches to
      treatment. Evolution of a standardized and validated counting methodology and
      significant advances in procuring skin biopsies have opened up a wide spectrum of
      applications that make the technology easy to apply in practice. The application
      of this technology may lead to early detection of many common peripheral nerve
      diseases and an enhanced understanding of disease onset and progression. In this
      article we review the state of current research and clinical practice in the use
      of skin biopsies and epidermal nerve densities.

PMID- 18090916
TI  - Predictive and prognostic markers in neuro-oncology.
AB  - Over the past few years molecular assays have been introduced to aid in typing
      and grading of gliomas. This is the result of improved understanding of these
      tumors at the molecular level. In particular, the presence or absence of combined
      1p/19 loss in oligodendroglial tumors, epidermal growth factor receptor
      amplification, epidermal growth factor receptor vIII mutations in grade III
      tumors and glioblastoma multiforme, and MGMT promoter gene methylation in
      glioblastoma multiforme are now being used to tailor treatment decisions in
      patients. However, the application of these tests is far from straightforward,
      and certain standards are required before any test can be introduced in the daily
      management of patients. Some of these requirements concern inter- and intratest
      variability, including whether a test gives the same results if repeated in the
      same or in another laboratory or when different methodologies are used (e.g. loss
      of heterozygosity vs fluorescence in situ hybridization and a polymerase chain
      reaction-based test vs immunohistochemistry). The sensitivity and specificity of
      a test (or negative and positive predictive value) indicate the likelihood that
      the test results are positive if the disease is present and the likelihood that
      the disease is present if the test results are positive. Studies on these test
      characteristics usually require the presence of a gold standard to which new
      tests should be compared. Last but not least there is the question of what added
      value the test has; this criterion determines the clinical usefulness of the
      assay and why some recently introduced molecular assays need to be scrutinized.

PMID- 18090917
TI  - Patterned neuropathologic events occurring in hyh congenital hydrocephalic mutant
      mice.
AB  - Hyh mutant mice develop long-lasting hydrocephalus and represent a good model for
      investigating neuropathologic events associated with hydrocephalus. The study of
      their brains by use of lectin binding, bromodeoxyuridine labeling,
      immunochemistry, and scanning electron microscopy revealed that certain events
      related to hydrocephalus followed a well-defined pattern. A program of
      neuroepithelium/ependyma denudation was initiated at embryonic day 12 and
      terminated at the end of the second postnatal week. After the third postnatal
      week the denuded areas remained permanently devoid of ependyma. In contrast, a
      selective group of ependymal areas resisted denudation throughout the lifespan.
      Ependymal denudation triggered neighboring astrocytes to proliferate. These
      astrocytes expressed particular glial markers and formed a superficial cell layer
      replacing the lost ependyma. The loss of the neuroepithelium/ependyma layer at
      specific regions of the ventricular walls and at specific stages of brain
      development would explain the fact that only certain brain structures had
      abnormal development. Therefore, commissural axons forming the corpus callosum
      and the hippocampal commissure displayed abnormalities, whereas those forming the
      anterior and posterior commissures did not; and the brain cortex was not
      homogenously affected, with the cingular and frontal cortices being the most
      altered regions. All of these telencephalic alterations developed at stages when
      hydrocephalus was not yet patent at the lateral ventricles, indicating that
      abnormal neural development and hydrocephalus are linked at the etiologic level,
      rather than the former being a consequence of the latter. All evidence collected
      on hydrocephalic hyh mutant mice indicates that a primary alteration in the
      neuroepithelium/ependyma cell lineage triggers both hydrocephalus and
      abnormalities in telencephalic development.

PMID- 18090918
TI  - Postmortem delay has minimal effect on brain RNA integrity.
AB  - The Bryan Alzheimer Disease Research Center obtains postmortem human brain tissue
      from patients with Alzheimer disease (AD) and cognitively normal control subjects
      for molecular and genetic research programs. A growing body of research suggests
      that variations in gene transcript levels may contribute to the onset and
      progression of disease. Identifying how the regulation of gene expression may
      affect AD requires the use of high-quality mRNA from banked human brains. The
      present study was conducted to establish the quality and suitability of available
      banked brain tissue for future gene expression studies. We chose 32 AD cases with
      Braak stage IV, V, or VI. These AD cases were matched to 36 normal control cases
      by age and sex when possible. Multiple regions from each brain were sampled,
      including frontal cortex, temporal cortex, occipital cortex, and cerebellum.
      Hippocampus was also available for study from 14 control cases. A comparison of
      several antemortem and postmortem variables, such as postmortem interval, agonal
      state, ventricular cerebrospinal fluid pH, and cause of death were analyzed. RNA
      was isolated from at least 1 area from every brain and most brains yielded intact
      RNA from all regions tested. Analysis of the clinical variables did not reveal
      any features that correlated with the ability to recover intact mRNA. We conclude
      that undegraded mRNA may be isolated from most brain regions many hours
      postmortem and that neither the pH of ventricular fluid nor postmortem interval
      is predictive of mRNA integrity.

PMID- 18090919
TI  - A novel cerebral microangiopathy with endothelial cell atypia and multifocal
      white matter lesions: a direct mycoplasmal infection?
AB  - We present 3 sporadic cases of a subacute to chronic, progressive motor (i.e.
      weakness, ataxia, spasticity, dysarthria, and dysphagia) and cognitive disorder
      in adults of both sexes, without proven immunocompromise or malignancy.
      Neuroimaging studies revealed tiny calcifications with atrophy of the cerebrum,
      pons, and midbrain in 1 patient, cerebral atrophy in another, and cerebral
      atrophy and periventricular white matter hyperintensities in the third. Clinical
      diagnoses included cortico-pontine-cerebellar degeneration, mixed
      neurodegenerative disorder, progressive supranuclear palsy, diffuse Lewy body
      disease, and Lyme disease. One atrophic brain revealed widely disseminated,
      millimeter-sized gray lesions in cerebral white matter and obscured anatomic
      markings of the basis pontis. The most conspicuous microscopic feature in all was
      capillaries with focally piled up endothelial nuclei, some of which appeared to
      be multinucleated, or enlarged, hyperchromatic crescentic single nuclei. Although
      seen mostly without associated damage, they were also noted with white matter
      lesions displaying vacuolation, demyelination, spheroids, necrosis, vascular
      fibrosis, and mineralization; these were most severe in the basis pontis.
      Immunostains and probes to herpes simplex virus-I, -II, and -8; adenovirus,
      cytomegalovirus, varicella-zoster, Epstein-Barr virus, measles, JC virus, and
      herpes hominis virus-6 were negative. Electron microscopy revealed no virions in
      endothelial cells with multilobed or multiple nuclei and duplicated basal
      laminae. However, mycoplasma-like bodies, mostly 400 to 600 nm in size, were
      found in endothelial cell cytoplasm and capillary lumina. Platelets adhered to
      affected endothelial cells. Polymerase chain reaction and immunohistochemistry of
      fixed samples for Mycoplasma fermentans were negative; other species of
      Mycoplasma remain viable pathogenic candidates.

PMID- 18090920
TI  - Intratumoral distribution of 1p loss in oligodendroglial tumors.
AB  - The favorable response of oligodendrogliomas correlates well with characteristic
      chromosomal losses, of which loss of the short arm of chromosome 1 is most
      predictive. Oligodendrogliomas are histopathologically heterogeneous tumors and,
      in addition to the classic honeycomb histology, fields of nonclassic histology
      are often encountered. Information about the distribution of 1p loss in various
      regions of oligodendroglioma is, therefore, important to interpret findings in
      tumor biopsies. In this study we investigated the distribution of 1p loss in
      multiple fields in 24 biopsy specimens of oligodendroglioma consisting of classic
      and nonclassic histology by fluorescent in situ hybridization and loss of
      heterozygosity analysis. By fluorescent in situ hybridization analysis, loss of
      1p was found in all fields examined in 37% of the tumor samples, and no loss was
      detected in 46%. In fields of classic oligodendroglial and polar spongioblastoma
      like histology, significantly more loss for 1p was found (p < 0.001 and p < 0.01,
      respectively). Although fluorescent in situ hybridization analysis indicated
      heterogeneity for 1p loss in the other 17% of tumors, loss of heterozygosity
      analysis of these samples pointed to homogeneity of 1p status in all fields. The
      1p status of the fields with classic histology significantly correlated with the
      status of the other fields in the same tumors (Spearman's rho 0.918, p < 0.001).
      These results point to genotypic homogeneity for 1p in oligodendroglial tumors.

PMID- 18090921
TI  - Oligodendrocyte generation is differentially influenced by toll-like receptor
      (TLR) 2 and TLR4-mediated intraspinal macrophage activation.
AB  - Oligodendrocytes are vulnerable to CNS injury and disease. Because
      oligodendrocytes myelinate CNS axons, their death leads to demyelination and
      impaired axon conductance, which in turn contribute to neurologic deficits.
      Replacing oligodendrocytes requires proliferation and differentiation of
      endogenous NG2+ progenitor cells, a process that can be potently influenced by
      activated macrophages, which are present in most CNS pathologies. To examine the
      relationship between oligodendrocyte generation and macrophage activation in
      vivo, we compared the extent of oligodendrocyte loss and NG2 cell proliferation
      and differentiation after intraspinal microinjection of lipopolysaccharide (a
      Toll-like receptor-4 agonist) or zymosan (Toll-like receptor-2 agonist) in rats.
      Controls included injecting vehicle (sterile PBS; negative control) or
      lysolecithin (positive control for NG2 cell proliferation and oligodendrocyte
      differentiation). By 14 days postinjection, lipopolysaccharide injection sites
      displayed a sigficant rise in NG2 cell proliferation and oligodendrocyte
      differentiation, which exceeded that in vehicle and lysolecithin injections.
      Additionally, upregulated ciliary neurotrophic factor expression was present in
      lipopolysaccharide lesions. In contrast, zymosan-activated macrophages produced
      complete oligodendrocyte loss without stimulating NG2 cell proliferation,
      oligodendrocyte replacement, or ciliary neurotrophic factor expression. Zymosan
      also evoked a delayed lesion expansion and primary demyelination of intact
      myelinated axons around the lesions. These results clearly delineate the
      dichotomous potential of macrophage activation for influencing NG2 cell
      proliferation and oligodendrocyte differentiation. Because endogenous Toll-like
      receptor ligands are often present in injured CNS tissue, these results shed
      light on possible mechanisms that restrict oligodendrocyte replacement to
      specific domains of CNS trauma or disease sites.

PMID- 18090923
TI  - Evidence that TDP-43 is not the major ubiquitinated target within the
      pathological inclusions of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease
      characterized by the presence of various types of ubiquitinated inclusions in the
      cytoplasm of affected motor neurons. The identification of the ubiquitinated
      targets within these inclusions has represented a major challenge, as this may
      provide new gene candidates and/or clues to understanding the neurodegenerative
      mechanism(s) underlying the disease. As such, the nuclear factor TAR DNA-binding
      protein (TDP-43) was recently identified as a component of ubiquitinated skein
      like inclusions and round inclusions in ALS. This identification combined with
      biochemical evidence led to the suggestion that TDP-43 is the key ubiquitinated
      target and major disease protein in ALS. Here, using 3-dimensional deconvolution
      imaging, we have obtained remarkable resolution of skein-like inclusions and
      round inclusions in ALS. Surprisingly we have found that in contrast to current
      thinking, TDP-43 is not the major ubiquitinated target within these types of
      inclusions. These findings raise the possibility that TDP-43 may not necessarily
      be the key disease protein in ALS and indicate that the major target(s) of
      ubiquitination remain to be identified.

PMID- 18090922
TI  - Clinicopathologic correlations in a large Alzheimer disease center autopsy
      cohort: neuritic plaques and neurofibrillary tangles "do count" when staging
      disease severity.
AB  - There is uncertainty regarding the association of cognitive decline in Alzheimer
      disease (AD) with classic histopathologic features- neurofibrillary tangles
      (NFTs) and "neuritic" amyloid plaques (NPs). This uncertainty fuels doubts about
      the diagnostic importance of NFTs and NPs and leads to confusion regarding
      hypotheses of AD pathogenesis. Three hundred ninety subjects who underwent
      longitudinal premortem clinical workup and postmortem quantitative
      neuropathologic assessment served as the group to address this issue. Subjects
      with concomitant brain disease(s) were analyzed independently to more accurately
      assess the contribution of distinct pathologies to cognitive decline. More than
      60% of patients of all age groups had important non-AD brain pathologies.
      However, subjects without superimposed brain diseases showed strong correlations
      between AD-type pathology counts (NFTs > NPs) and premortem Mini-Mental State
      Examination scores. The observed correlation was stronger in isocortex than in
      allocortex and was maintained across age groups including patients older than 90
      years. A theoretical model is proposed in which our results are interpreted to
      support the "amyloid cascade hypothesis" of AD pathogenesis. Our data show that
      there are many important contributory causes to cognitive decline in older
      persons. However, NFTs and NPs should not be dismissed as irrelevant in AD based
      on clinicopathologic correlation.

PMID- 18090925
TI  - 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICA-riboside) as a
      targeting agent for therapy of patients with acute lymphoblastic leukemia: are we
      there and are there pitfalls?

PMID- 18090926
TI  - Splenic papillary angioendothelioma in a 6-year-old girl.
AB  - Papillary angioendothelioma is a rare, low-grade neoplasm of lymphatic channels
      that usually presents intradermally. We report the case of a 6-year-old girl with
      isolated splenomegaly and symptoms of early satiety and weight loss, whom was
      found to have a splenic papillary angioendothelioma. Preoperative abdominal
      computed tomography scan showed an irregular, heterogeneous mass; a tagged red
      cell scan ruled out a hemangioma, whereas a positron emission tomography scan
      showed mildly increased uptake. Subsequent surgery and pathologic assessment
      revealed a papillary angioendothelioma (Dabska tumor) within lymphatic spaces.
      The child has no evidence of recurrence or metastases 1 year postoperatively.

PMID- 18090927
TI  - Different rates of clinical trial enrollment between adolescents and young adults
      aged 15 to 22 years old and children under 15 years old with cancer at a
      children's hospital.
AB  - BACKGROUND: Over the last 30 years significant strides have been made in cure
      rates for children with cancer, but these improvements have not been seen in
      adolescents and young adults. The reasons for this lack of progress are
      multifactorial, but it is clear greater cure rates are correlated with controlled
      clinical trials. Our objective was to see if pediatric patients over the age of
      15 had a lower rate of clinical trial enrollment, and if so, why. METHODS: We
      retrospectively analyzed the clinical data on all patients with new oncology
      diagnoses at Children's Hospital of Pittsburgh (CHP) diagnosed over a 5-year
      period from July 2001 to June 2006. RESULTS: Six hundred and forty new oncology
      patients were seen at CHP over this time, 501 under 15 years old and 139 patients
      aged 15 to 22. Thirty-six percent of all patients were treated on a clinical
      trial, including 38% of the younger patients and 27% of the older patients
      (P=0.03). Fifty-seven percent in the older group were not enrolled on a clinical
      trial because one was not available versus 41% in the younger group (P=0.04).
      There were no significant differences between the age groups when other reasons
      were analyzed. CONCLUSIONS: A significantly lower proportion of adolescents and
      young adults patients (aged 15 to 22) were placed on a treatment trial than
      younger patients. The lack of an open clinical trial was the main reason for this
      deficit. Interventions to address this discrepancy need to be instituted on a
      national level.

PMID- 18090928
TI  - Exploratory analysis of Fas gene polymorphisms in pediatric osteosarcoma
      patients.
AB  - Defective apoptosis signaling by the Fas pathway has carcinogenic implications.
      We analyzed 123 pediatric patients with osteosarcoma for Fas single nucleotide
      polymorphisms: 2 of the promoter region (-1377 G>A and -670 A>G) and 2 of the
      coding region (exon 3 18272 A>G and exon 7 22628 C>T). As a comparison group, we
      used 510 adults without a history of cancer. We found an increased risk of
      osteosarcoma associated with the heterozygous genotype Fas exon 3 AG (genotype
      frequency 19.5% in cases vs. 12.0% in controls, P=0.028; adjusted odds ratio=1.6,
      95% confidence interval=0.9-2.7], and this association was more pronounced in non
      Hispanic whites (20.6% in cases vs. 10.1% in controls, P=0.014; adjusted odds
      ratio=2.3, 95% confidence interval=1.2-4.6). Additionally, the frequency of the
      variant allele (exon 3 G) was significantly higher in cases than in controls for
      both the entire group and non-Hispanic whites (P=0.046 and P=0.030,
      respectively). We found no significant association between osteosarcoma risk and
      the other Fas polymorphisms. This study suggests an association between the Fas
      exon 3 A>G polymorphism and osteosarcoma risk; however, further study is needed
      with pediatric controls and a larger sample size.

PMID- 18090929
TI  - Congenital amegakaryocytic thrombocytopenia-3 novel c-MPL mutations and their
      phenotypic correlations.
AB  - Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare bone marrow failure
      syndrome associated with thrombocytopenia and a tendency to progress to aplastic
      anemia. Mutations in the c-MPL gene encoding for thrombopoietin receptor have
      been identified in the majority of the patients. Previous studies suggest a
      genotype-phenotype correlation wherein the severity of the disease depends on the
      type of mutation present and residual thrombopoietin receptor activity. The
      present study describes the clinical and genetic findings on a series of 7
      patients with CAMT, 3 of them siblings. The patients were homozygous for 5
      mutations in the c-MPL gene, including 3 unique ones: c.212+5G>A, C76T, and
      G1162C. The clinical picture was variable; 1 patient who was homozygous for a
      nonsense mutation in exon 1 (C76T) developed infantile acute lymphoblastic
      leukemia, whereas patients who were homozygous for a splice-site mutation
      (c.212+5G>A) expressing both normal and mutated transcripts had a milder clinical
      course. As previously suggested, c-MPL mutation analysis in CAMT patients helps
      to predict the clinical course and to provide optimal therapy.

PMID- 18090930
TI  - The development of a novel protocol for the treatment of de novo childhood acute
      myeloid leukemia in a single institution in Taiwan.
AB  - From November 1, 1995 to July 31, 2004, 49 children with de novo acute myeloid
      leukemia (AML) were treated at our institution. One patient who was treated by a
      different protocol was excluded. In total, 48 patients with de novo AML were
      enrolled in this study. Forty-two patients with AML other than acute
      promyelocytic leukemia (non-APL) were treated consecutively with 2 novel
      protocols: Mackay Memorial Hospital (MMH)-AML-96, designed as a pilot phase, and
      Taiwan Pediatric Oncology Group (TPOG)-AML-97A, on the basis of MMH-AML-96 with
      minor modifications. Six patients with APL were treated consecutively with 2
      protocols, TPOG-APL-97 and APL-2001. As of July 31, 2006, the remission rates
      were 79%, 92%, and 98% after 1, 2, and 3 courses of induction therapy,
      respectively. The 5-year overall survival was 64%+/-6.9% (SE), and the 5-year
      event-free survival was 60%+/-7.1%; for non-APL AML, the rates were 62%+/-7.5%
      and 59%+/-7.6%; for APL, 83+/-15.2 and 67+/-19.3%. Among the factors analyzed, a
      complete remission achieved after 1 course of induction therapy, lactate
      dehydrogenase <500 IU/L at diagnosis, patients without invasive fungal infection
      during chemotherapy, and male sex were associated with a favorable outcome.

PMID- 18090931
TI  - Occurrence of a spinal anaplastic pilocytic astrocytoma and a supratentorial PNET
      in an adolescent.
AB  - A 15-year-old girl was diagnosed with a spinal anaplastic pilocytic astrocytoma.
      The histologic features were similar to pilocytic astrocytoma WHO grade I, but
      with an increased mitotic rate, high nuclear pleomorphism, microvascular
      proliferation, and necrosis. The tumor was subtotally resected and treated with
      chemotherapy and irradiation. Four years after diagnosis no local progression was
      seen. At the age of 17, the patient developed a supratentorial primitive
      neuroectodermal tumor. We report the first case of a primary anaplastic pilocytic
      astrocytoma and primary primitive neuroectodermal tumor occurring in the same
      patient.

PMID- 18090932
TI  - Wiskott-Aldrich syndrome is an important differential diagnosis in male infants
      with juvenile myelomonocytic leukemialike features.
AB  - A newborn presented with thrombocytopenia at birth and subsequently developed
      leukocytosis, monocytosis, and mild hepatomegaly. The bone marrow was
      normocellular with dysplasia and spontaneous granulocyte-monocyte colony
      formation was demonstrated. These findings fulfilled the diagnostic criteria of
      juvenile myelomonocytic leukemia. Then he developed atopic dermatitislike eczema,
      which led to the consideration of Wiskott-Aldrich syndrome (WAS). Lack of
      intracellular WASP expression and WASP gene mutation confirmed the diagnosis of
      WAS. After stem cell transplantation, he is alive in good condition with normal
      WASP expression. WAS should be considered as a differential diagnosis in male
      infants with juvenile myelomonocytic leukemialike features.

PMID- 18090933
TI  - Early acute myeloblastic leukemia treatment for childhood myelodysplastic
      syndrome with t(3;5) (NPM/MLF1).
AB  - Myelodysplastic syndromes (MDS) in childhood are rare hematologic diseases. MDS
      with t(3;5) (NPM/MLF1) is an unusual subtype without a well-defined clinical and
      prognostic pattern. A poor outcome has been reported, suggesting that
      hematopoietic transplantation is the only treatment option. Here in we described
      a 2-year-old child diagnosed with the disease, without a suitable hematopoietic
      donor, treated early in the disease with chemotherapy. He is alive and well 4
      years after the end of treatment. This unusual MDS needs further studies to
      better understand the disease.

PMID- 18090934
TI  - A case of a ewing sarcoma family tumor in the urinary bladder after treatment for
      acute lymphoblastic leukemia.
AB  - We report the first case of a tumor of the Ewing sarcoma family of tumors arising
      from the urinary bladder 3 years after chemotherapy for acute lymphoblastic
      leukemia. A 16-year-old boy complained of macrohematuria and dysuria during the
      posttreatment follow up of his acute lymphoblastic leukemia. Ultrasonography and
      computed tomography revealed a 1-cm sized intravesical tumor. The tumor was
      transurethrally resected with no residual tumor at the margin. Histopathologic
      analyses revealed a small round blue cell tumor with positive staining for CD99
      antibody. EWS-FLI1 fusion transcripts were detected in the tumor tissue by
      reverse transcriptase polymerase chain reaction. These findings support the
      diagnosis of Ewing sarcoma family of tumor. After adjuvant multidrug
      chemotherapy, the patient has shown no evidence of disease for more than 2 years.

PMID- 18090935
TI  - Long-term survival of pancreatoblastoma in children.
AB  - Pancreatoblastoma is an extremely rare pancreatic tumor of childhood. We report
      our experience in 2 patients with pancreatoblastoma who had long-term survival
      and review the literature with a focus on chemotherapy in pancreatoblastoma with
      vascular invasion. The cases were 7-year-old and 4-year-old girls who complained
      of an abdominal mass without jaundice. Laboratory findings including serum alpha
      fetoprotein were within normal limits. Radiologic investigations revealed a mass
      in the pancreas with vascular invasion. After surgical resection, postoperative
      chemotherapy included cisplatin, doxorubicin, ifosfamide, and etoposide. They
      have now been well for 7 years without recurrence.

PMID- 18090936
TI  - Renal cell carcinoma in a child presented as bilateral femur neck fractures
      caused by severe vitamin D deficiency.
AB  - An Ethiopian girl 14 years and 11 months of age presented with bilateral
      transcervical hip fractures. Workup revealed severe vitamins D and C deficiencies
      with secondary hyperparathyroidism. Imaging studies showed bilateral radiolucent
      metaphyseal bands with multiple lytic lesions in long bones. A mass in the right
      flank was found to be renal cell carcinoma (RCC). Currently, 9 months postsurgery
      and supplemental therapy, the patient is fully ambulatory and free of pain. This
      first report of asymptomatic RCC in severely vitamin D deficient child highlights
      the relation of RCC to vitamin D deficiency and emphasizes the importance of
      careful evaluation of these children.

PMID- 18090937
TI  - Preoperative chemotherapy and intraoperative radiofrequency ablation for
      unresectable solid pseudopapillary tumor of the pancreas.
AB  - Solid pseudopapillary tumor (SPT) is rare primary tumor of the pancreas with low
      malignant potential affecting adolescent or young women. Radical surgical
      resection is the definitive treatment for long-term survival even in the patients
      with metastases. We report a case of 14-year-old girl who presented with
      unresectable SPT of the pancreas. She received preoperative chemotherapy with
      cisplatinum, ifosfamide, etoposide, and vincristine followed by intraoperative
      radiofrequency ablation of metastatic liver lesions with surgical resection of
      the primary tumor successfully. We demonstrate that all attempts should be made
      to resect or ablate the primary as well as the metastatic lesions for long-term
      survival.

PMID- 18090938
TI  - Melanotic neuroectodermal tumor of infancy in the femur: a case report and review
      of the literature.
AB  - Melanotic neuroectodermal tumor of infancy (MNTI) is an uncommon neoplasm that
      most often affects the maxilla in the first year of life. MNTI occurring in the
      long bones is extremely rare, with only 2 cases reported in the medical
      literature. Here we report a case of MNTI in the right femur of a 5-month-old
      infant who underwent neoadjuvant chemotherapy followed by limb-salvage surgery.

PMID- 18090939
TI  - Wilms tumor associated with hirschsprung disease.
AB  - Hirschsprung disease (HD) has been associated with multiple renal malformations.
      We describe a child with HD who also had Wilms tumor (WT). Because the RET
      protooncogene, the major susceptibility gene for HD, also plays a role in normal
      kidney development and in the multiple endocrine neoplasia type 2 cancer
      syndrome, we analyzed our patient's constitutional DNA for mutations in RET
      commonly found in multiple endocrine neoplasia type 2A. Although this limited
      evaluation failed to show abnormalities, we speculate that comprehensive analysis
      of the RET gene may identify mutations to account for the development of WT in
      this and other children with WT.

PMID- 18090941
TI  - Spontaneous gastric perforation in a child with Burkitt lymphoma.

PMID- 18090940
TI  - Diaphragmatic mesothelial cyst in a child with Fanconi aplastic anemia.
AB  - Fanconi aplastic anemia (FAA), an inherited form of bone marrow failure syndrome,
      is characterized by progressive bone marrow failure and high risk of developing a
      malignancy. One or more congenital malformations may be detected in at least 90%
      of the affected individuals. Despite many forms of congenital malformations in
      FAA, there are no reports of coexisting FAA and diaphragmatic mesothelial cyst.
      Here, we report a 7-year-old female patient with FAA is associated with
      diaphragmatic mesothelial cyst.

PMID- 18090942
TI  - Large volume leukapheresis with the Cobe Spectra AutoPBSC in a 7-kg child.

PMID- 18090943
TI  - About megadose methylprednisolone.

PMID- 18090944
TI  - Kikuchi-fujimoto disease associated with extreme leukopenia and thrombocytopenia
      in an adolescent boy.

PMID- 18090946
TI  - Diagnosis of epilepsy over the course of the disease.
AB  - BACKGROUND: At the onset of the disease, differential diagnosis should be
      established between an epileptic seizure and a series of paroxysmal phenomena,
      such as syncope, pseudoseizure, or migraine aura, which may manifest with similar
      symptoms. But even when the initial differential diagnosis is established
      rigorously, we will see that it is often necessary to reconsider the diagnosis of
      epilepsy during the course of the disease. REVIEW SUMMARY: Prospective studies
      analyzing initial recognition of epilepsy found that on half of occasions the
      diagnosis was reached late, when the patient had already suffered repeated
      seizures. On other occasions, it is noted that, although the diagnosis of
      epilepsy was correct, the epileptic syndrome of the patient was classified
      erroneously, which can lead to inappropriate management. There are a number of
      reasons that can explain these delays or errors in diagnosis, and we will devote
      this entire article to their discussion. CONCLUSIONS: Based on a detailed medical
      history and with the aid of the electroencephalogram and magnetic resonance
      imaging, the diagnosis of epilepsy can be made and the specific epileptic
      syndrome identified in many patients from the time of the first seizure. However,
      various studies show that it is often necessary to modify the initial diagnosis
      during the follow-up of a patient because of progression of the disease itself
      (infantile stage), a previous diagnostic error, or because of diagnostic
      difficulties or inadequate interpretation of tests such as the
      electroencephalogram or magnetic resonance imaging.

PMID- 18090947
TI  - Diagnostic problems in the initial assessment of epilepsy.
AB  - BACKGROUND: On most occasions, the diagnosis of seizures and epilepsy is
      considered in cases of temporary disturbance of neurologic function. In this
      clinical situation, the physician in charge (neurologist, emergency physician,
      general practitioner, intensivist, cardiologist, psychiatrist, etc.) should
      establish the differential diagnosis with other pathologies that can also cause
      transient neurologic disturbances. REVIEW SUMMARY: We will review the relevant
      literature about the diagnostic process and the differential diagnosis of
      epileptic seizures and epilepsy at the onset of the disease, and the medical
      consequences of an incorrect diagnosis. CONCLUSION: Neurologists and non
      neurologists often diagnose epilepsy. The diagnostic challenge consists of
      correctly interpreting the medical history, characteristics of the episodes and
      physical and neurologic examination, and properly using and interpreting
      supplemental paraclinical tests.

PMID- 18090948
TI  - Antiepileptic drugs: from scientific evidence to clinical practice.
AB  - INTRODUCTION: Evidence-based medicine establishes guidelines for clinical
      decision-making in which priority is given to processes that have the highest
      level of evidence. Although these guidelines provide valuable general guidance,
      the information is partial, because oftentimes obtaining evidence on
      antiepileptic drugs is promoted by commercial expectations and not by clinical
      priorities. Furthermore, the guidelines tend to classify different types of
      epilepsy into large groups, often without contemplating the different syndromes.
      Expert opinions are subject to criticism on the basis of methodology and their
      authoritarian aspect, although they can supplement medical literature and advice
      on specific clinical situations quickly and efficiently. OBJECTIVES: This review
      seeks to incorporate scientific evidence and expert opinion into drug treatment
      for epilepsy. METHODS: To analyze this issue, a review of the literature was
      conducted by means of PubMed searches. CONCLUSION: We have found that in all
      types of epilepsy [except in focal epilepsy in children where a new drug
      (oxcarbamazepine) is considered to be the first choice for initial treatment],
      classic drugs (valproic acid in idiopathic generalized epilepsy and carbamazepine
      in focal epilepsy) are recommended as long as there are no contraindications due
      to adverse effects or concomitant use of other drugs that interact with the
      antiepileptics. However, despite the general recommendations, it can be deduced
      from the studies and reflections on the subject that the decision as to whether
      to start treatment or not, as well as the drug of choice, must be made on a case
      by-case basis, taking into account the patient's personal and social
      circumstances.

PMID- 18090949
TI  - Surgery and electrical stimulation in epilepsy: selection of candidates and
      results.
AB  - BACKGROUND: Despite the correct use of antiepileptic drugs, control of seizures
      is not possible in 20% to 30% of people with epilepsy. This group of patients is
      considered to suffer from drug-resistant epilepsy, a clinical situation that can
      be caused by certain syndromes in which surgery can be used to bring the seizures
      under control. REVIEW SUMMARY: Determining the suitability of the surgical
      treatment and the best approach always requires a full assessment, which includes
      video-electroencephalogram (EEG) monitoring, neuropsychological examination, and
      structural magnetic resonance imaging. In some patients it may be necessary to
      perform functional imaging tests and intracranial electrode recordings. These
      tests make it possible to confirm that the patient does indeed have epilepsy,
      identify the type of epilepsy, determine the severity of the seizures, and locate
      the epileptogenic zone. The best surgical results are obtained in patients with
      small epileptogenic lesions which can be totally resected. Nevertheless, in many
      patients in whom complete control is not achieved after surgery, the improvement
      in control of the seizures also has a positive impact on their quality of life.
      Some surgical techniques (partial resections, corpus callosotomy, subpial
      transection, electrical stimulation of the vagus nerve, and deep brain
      stimulation) have a palliative effect. CONCLUSION: The aim of this review is to
      update knowledge on the indications for surgery and electrical stimulation in the
      management of epilepsy.

PMID- 18090950
TI  - Clinical implications of mechanisms of resistance to antiepileptic drugs.
AB  - BACKGROUND: Despite the currently available armamentarium of antiepileptic drugs,
      seizures are not adequately controlled in about one-third of epileptic patients.
      The mechanisms of antiepileptic drug resistance are multiple and not fully
      clarified. METHODS: We conducted a literature search in PubMed and the Cochrane
      Library databases with the terms: "Drug Resistance" [MeSH] and "Epilepsy" [MeSH],
      LIMITS: added to PubMed in the last 5 years, only items with abstracts, English,
      Spanish, Humans. REVIEW SUMMARY: It is currently known that membrane transporter
      proteins are increased in brain tissue of refractory epileptic patients and in
      animal models of epilepsy and that overexpression of these transporters and their
      inhibition are correlated with a reduction and an increase, respectively, of
      epileptic drugs in epileptic tissue (pharmacokinetic hypothesis). It has also
      been shown that alterations in voltage-gated sodium channels and GABAA receptors
      are responsible for resistance to some epileptic drugs. These changes may be
      constitutional (genetically determined) or acquired (as a consequence of the
      seizures themselves or disease progression) and may seem alone or combined with
      each other (pharmacodynamic hypothesis). Associations have been shown between
      certain genetic polymorphisms and resistance to epileptic drugs, and although
      they have not been replicated by all authors, they constitute a very attractive
      line of research. More detailed knowledge of these molecular mechanisms will
      probably lead to the development of new strategies for pharmacological treatment
      of epilepsy.

PMID- 18090951
TI  - Genetic causes of epilepsy.
AB  - BACKGROUND: The contribution of genetic factors to the origin of different
      epilepsies is a fact established by epidemiological, clinical, and molecular
      studies. These studies have made it possible to identify numerous mutations in
      different genes that cause or predispose to the development of certain types of
      epilepsy. REVIEW SUMMARY: The study of single-gene epilepsies has contributed
      relevant data regarding the pathophysiology of epilepsy. Most of these genes
      encode voltage- or ligand-gated ion channels. Other single-gene epilepsies are
      related to mutations that provoke alterations in neuronal maturation and
      migration during embryonic development. Nevertheless, the most common forms of
      epilepsy are not caused by single mutations but by a combination of
      polymorphisms, most of which are unknown, that generate an alteration in neuronal
      excitability. In some syndromes, genetic alterations and their consequences have
      made it possible to explain the therapeutic response to different drugs.
      Therefore, the progress being made in genetics is changing the classification and
      diagnosis of epilepsy; moreover, it can sometimes influence the choice of
      treatment. CONCLUSION: The advances made in genetic knowledge of epilepsy have
      led to the description of new epilepsy syndromes and to a better characterization
      of known ones. However, the genes responsible for the most common forms of
      idiopathic epilepsy remain mostly unknown. This means that for the time being, in
      clinical practice, genetic diagnosis is limited to uncommon syndromes and to
      cases in which treatment decisions or genetic counseling can be derived from the
      diagnosis.

PMID- 18090952
TI  - Special situations in epilepsy: women and the elderly.
AB  - BACKGROUND: The treatment of epilepsy requires special considerations for certain
      groups of patients. In this review we will address some of these situations, such
      as epilepsy in women and the elderly. REVIEW SUMMARY: Epilepsy in women has
      specific implications, because a significant proportion of women will present
      epilepsy during reproductive age, affecting contraception, pregnancy, fetal
      development, and lactation. Moreover, the influence of sex hormones on the
      evolution of epilepsy is known, as well as the effects of treatment with
      antiepileptic drugs on fertility, endocrine function and possible adverse effects
      on weight, to say nothing of cosmetic aspects, sexual function, and bone
      metabolism. All these factors must be taken into account in the treatment and
      monitoring of women with epilepsy. The incidence of epilepsy is greater in the
      elderly than in other population groups and is under diagnosed. The special
      characteristics of this population, such as the presence of concomitant diseases
      or greater sensitivity to adverse effects, requires a thorough knowledge of the
      different options of antiepileptic drugs for each situation. CONCLUSION: This
      article reviews the different types of epilepsy most frequently observed in the
      elderly, etiology, clinical symptoms, diagnosis, prognosis, and treatment.

PMID- 18090953
TI  - Status epilepticus: evidence and controversy.
AB  - Status Epilepticus (SE) is a potential and relatively common complication of
      epileptic seizures. Traditionally, SE was defined as 30 minutes of continuous
      seizure activity or a series of seizures without return to full consciousness
      between the seizures. As a practical rule, it is admitted that all patients
      arriving at the emergency room suffering from epileptic seizures could have SE
      and should be treated accordingly. It is well known that the longer an attack has
      lasted, the more difficult it is to control in the next 5 to 10 minutes. On the
      other hand, once an attack has lasted for over 5 to 10 minutes, it is unlikely to
      cease spontaneously. Ambulatory intervention should focus on this "therapeutic
      interval" in acute attacks with the use of first-line drugs such as the
      intramuscular, rectal, oral, and/or intranasal application of benzodiazepines
      (BZD). Treatment of SE is a medical emergency, which should include 3 priority
      objectives: (1) to stop the seizures; (2) to maintain internal homeostasis; and
      (3) to treat possible complications. Current consensus is that a BZD, notably
      lorazepam or diazepam, is the initial class of drug for the treatment of SE.
      Phenytoin, fosphenytoin, or valproate generally is agreed upon as the next drugs
      to be administered. Failure to respond to optimal BZD and phenytoin loading
      operationally defines refractory SE.

PMID- 18090957
TI  - Are clinical scoring systems for the diagnosis of group A beta-hemolytic
      streptococci pharyngitis useful?

PMID- 18090958
TI  - Living donor kidney transplantation.

PMID- 18090959
TI  - Medications don't work if patients don't take them.

PMID- 18090960
TI  - Diagnosis of group A beta-hemolytic Streptococcus using the Breese clinical
      scoring system.
AB  - This study was planned to determine the effectiveness of the Breese scoring
      system for the diagnosis of streptococcal pharyngitis and to evaluate its
      significance in different age groups. The research population was divided into
      two age groups. Group 1 consisted of children aged three and below and group 2
      comprised children over three years of age. All of them were then evaluated using
      both the Breese scoring system and throat swab cultures. In group 1, there was no
      difference between the mean Breese scores of group A beta-hemolytic Streptococcus
      (GABHS)-positive and negative patients. However, in group 2, the mean Breese
      scores were higher in GABHS-positive patients than in GABHS-negative patients (P
      < 0.001). The diagnostic value of the Breese scoring system in group 1 was
      sensitivity, 3.4%; specificity, 93.6%; positive predictive value, 18.2%; and
      negative predictive value, 70.1%. In group 2, sensitivity was 68.8%; specificity,
      82.5%; positive predictive value, 78.8%; and negative predictive value, 73.7%.
      The results indicate that the Breese scoring system is still a useful scoring
      system for streptococcal pharyngitis in children over three years of age, and may
      help in deciding whether or not to take a throat-swab culture. A score >29 can be
      used as an indication for antibiotherapy. So it seems to be a useful marker for
      decision-making regarding antibiotherapy in emergency departments.

PMID- 18090962
TI  - Clinical considerations and practical recommendations for the primary care
      practitioner in the management of anemia of chronic kidney disease.
AB  - Anemia is prevalent in patients with chronic kidney disease (CKD) and is a risk
      factor for poor disease outcome. Anemia acts as a risk multiplier, significantly
      increasing the risk of death in anemic versus nonanemic CKD patients with similar
      comorbidities. Erythropoiesis-stimulating agents (ESA) are a mainstay for the
      treatment of anemia in renal patients on dialysis, but recent data suggests that
      earlier treatment of anemia in CKD may delay the onset of end-stage renal disease
      (ESRD) and decrease mortality. Nonetheless, anemia of CKD is under-recognized and
      undertreated during the period before initiation of dialysis, when anemia
      correction may have the greatest impact on disease outcome. This report describes
      anemia in CKD and its association with diabetes, cardiovascular disease, and poor
      disease outcome, and offers suggestions for the recognition and treatment of
      anemia of CKD in the primary care setting.

PMID- 18090963
TI  - Living donor kidney transplantation: medical, legal, and ethical considerations.
AB  - The use of living donor kidneys has dramatically increased the number and success
      of kidney transplants across the world. But questions remain regarding the
      subjection of a healthy individual to surgery for the benefit of another. Donors
      do have medical and financial risks. The stigma of organ brokering remains today,
      with evidence of commercial transplantation in other countries. Here in the US,
      we are exposed to advertising for donors using the media. In the hope of
      increasing living donations, we run the risk of stretching altruism too far. In
      this manuscript, we highlight and discuss some of the current controversies
      surrounding living donor kidney transplantation across the world.

PMID- 18090964
TI  - Reduced fracture rates observed only in patients with proper persistence and
      compliance with bisphosphonate therapies.
AB  - Numerous studies have analyzed data from administrative claims databases to
      determine persistence and compliance with bisphosphonate therapy for
      osteoporosis; several of these studies have also examined how persistence and
      compliance with therapy affect fracture outcomes. All of the studies included in
      this review demonstrated that patients who were persistent or compliant with
      therapy had a decreased risk of fracture. None, however, adequately addressed the
      question of what level of persistence or compliance is necessary to obtain a
      reduced risk of fracture. There is agreement among studies that compliance and
      persistence rates are suboptimal for all osteoporosis treatments. Measures to
      improve persistence and compliance with osteoporosis medications are needed if
      patients are to achieve the full clinical benefit of treatment.

PMID- 18090965
TI  - Endophthalmitis associated with intravenous drug use.
AB  - Infectious complications related to i.v. drug use represent an important source
      of morbidity and mortality among this population. We report an informative case
      of endogenous endophthalmitis related to injection of cocaine mixed with lemon
      juice. Clinicians should remember that any visual change among patients using
      injection drugs warrants aggressive workup, including empiric antifungal therapy.
      Once the disease is identified, early vitrectomy should be considered.

PMID- 18090966
TI  - Papulonecrotic eruption in a 44-year-old-man.
AB  - A patient is described who presented with the acute onset of widely distributed
      necrotic papules mimicking pityriasis lichenoides et varioliformis acuta. A skin
      biopsy revealed granulomatous inflammation and spirochetes were demonstrated.
      Serologic testing confirmed infection with the Treponema pallidum. Syphilis is
      still a great imitator and its persistence as an infectious disease is reviewed.

PMID- 18090967
TI  - What is a miracle?
AB  - Based on arguments from theology and the philosophy of science, a miracle may be
      defined as: (1) a real, individual event, the occurrence of which must be (or
      must have been), at least in principle, susceptible to empirical verification;
      (2) an event which must be extremely unusual or historically unprecedented from
      the perspective of empirical scientific knowledge; (3) must evoke widespread
      wonder; (4) must be something freely given by God and not conjured; (5) must be
      understood as a special sign from God that transcends the bare facts of the case
      and communicates a spiritual message; and (6) must have been affirmed as a
      miracle by the community of believers to whom the message of the miracle must be
      addressed, at least indirectly.

PMID- 18090968
TI  - The history of thinking about miracles in the West.

PMID- 18090969
TI  - Miracles: a Christian theological overview.

PMID- 18090970
TI  - Eye on religion: miracles in the Chinese Buddhist tradition.

PMID- 18090971
TI  - Miraculous medical recoveries and the Islamic tradition.

PMID- 18090972
TI  - Eye on religion: a Jewish view on miracles of healing.

PMID- 18090973
TI  - The role of the physician in certifying miracles in the canonization process of
      the Catholic Church III.
AB  - Physicians play a very important role in the theological processes known as
      beatification canonization in the Catholic Church. In the first millennium of the
      Christian era, martyrs and other individuals who lived exemplary lives of
      Christian perfection in the opinion of the faithful in their locale were
      venerated as holy persons who had already obtained heaven upon their deaths.
      Thus, "saints" and their cults were created by action of local Christian
      communities. Bishops gradually recognized that such action was neither in the
      best interests of the local community of faithful Christians nor of its Church
      and Bishop. The creation of "saints" by local acclamatory action often leads to
      error, scandal, and heresy. In the beginning of the second millennium of the
      Christian era, the Popes gradually centralized this theological process under
      their direction. In the process which was developed, physicians were an essential
      group in certifying to the ecclesiastical authorities that a physical cure
      produced by a miracle was inexplicable by current medical knowledge. This paper
      subsequently describes this process of development as well as the special role of
      physicians in it.

PMID- 18090974
TI  - Waiting for a miracle... miracles, miraclism, and discrimination.
AB  - We argue that the use of publicly funded medical facilities for patients who are
      waiting for a miracle amounts to discrimination against atheists, agnostics and
      advocates, of faiths that do not accept miracle claims. The only exception is
      when this use can be justified by considerations that demonstrate that waiting
      makes it more likely that a miracle will occur and will aid the patient's
      recovery. Such justification can be grounded on considerations of faith or of
      reason. We consider both possibilities and suggest conditions of acceptability
      for both. In arguing this way, we steer a middle path between discrimination
      against atheists, agnostics, and advocates of faiths that do not accept miracle
      claims--miraclism--and a failure to respect religious belief.

PMID- 18090975
TI  - Responding to patient beliefs in miracles.

PMID- 18090976
TI  - Distinguishing denial from authentic faith in miracles: a clinical-pastoral
      approach.

PMID- 18090977
TI  - Miracles and medicine: an annotated bibliography.

PMID- 18090979
TI  - Patient's page. Milk myths and misconceptions.

PMID- 18090981
TI  - Malignancies in primary biliary cirrhosis.
AB  - (Table is included in full-text article.)PBC in the advanced stage, corresponding
      to PBC stage IV, was shown in the past to be associated with an increased
      incidence of hepatocellular carcinoma (HCC). There is currently a debate, about
      the increase in incidence of extrahepatic malignancies, as some, but not all
      studies reported these neoplasms to be more common, especially breast cancer,
      irrespective of the PBC disease stage. In this issue of the journal a case series
      is reported on the incidence of various malignancies in a cohort of 212 patients
      with PBC from Greece. Considering as reference the cancer registries of another
      Mediterranean Country, like Italy, we could suggest that the incidence of
      extrahepatic malignancy, breast included, is not increased in PBC patients.
      Indeed, a more accurate analysis of the literature, shows that higher incidence
      of breast cancer were reported only for PBC patients evaluated in the 1970s and
      early 1980s, for whom a contribution of immunosuppressive agents, largely under
      investigation at that time, could be speculated. PBC patients do not need,
      therefore, to be submitted to stricter surveillance programs for extrahepatic
      cancer than the general population. As far as the development of HCC is
      concerned, instead, PBC patients should undergo the usual surveillance reserved
      to other categories of cirrhotic patients, according to published guidelines for
      the management of HCC. Such surveillance should start only when PBC patients have
      reached disease stage IV (frank cirrhosis).

PMID- 18090982
TI  - Risk of hepatocellular carcinoma and extrahepatic malignancies in primary biliary
      cirrhosis.
AB  - OBJECTIVES: In primary biliary cirrhosis (PBC), the development of hepatocellular
      carcinoma (HCC) was thought to represent a rare complication. In contrast,
      extrahepatic malignancies have been reported to be significantly associated with
      PBC. The aim of this study was to determine the incidence of HCC and of
      extrahepatic malignancies in a large cohort of patients with PBC. METHODS: A
      total of 212 patients with documented PBC (19 men and 193 women) were followed up
      for a median of 6 (range, 1-23) years. RESULTS: In total, 23 (10.8%) cases of
      malignancy were diagnosed; eight (3.8%) patients with HCC and 15 (7.0%) with
      extrahepatic malignancies. PBC patients were found to have a 10-year risk of 4%
      for developing HCC and of 13% for developing extrahepatic malignancies. The risk
      for HCC was significantly higher in the PBC patients with cirrhosis (15% at 10
      years of follow-up). In contrast, the histologic stage of PBC does not influence
      the risk for extrahepatic malignancy. CONCLUSION: Our study confirms that there
      is a risk of HCC in Greek patients with PBC, particularly in patients with stage
      IV PBC. The risk of extrahepatic malignancies is higher than that of HCC, but it
      is not influenced by the histologic stage of the liver disease.

PMID- 18090983
TI  - Intrahepatic biliary cystadenoma: a need for radical resection.
AB  - BACKGROUND: Intrahepatic biliary cystadenoma (IBC) is a rare liver tumour, which
      has strong tendency to recur and malignant potential as it can progress to
      cystadenocarcinoma (IBCa). METHODS: From June 2003 to December 2006, four
      patients diagnosed with hepatic cystadenoma were operated on our Liver Surgical
      Unit. All patients were females with median age of 51 years (range 45-63 years).
      Liver resections included three left and one right hepatectomies. In two
      patients, IBC was diagnosed by abdominal imaging and serum tumour markers but the
      rest of the patients were initially misdiagnosed as simple cysts, treated by
      laparoscopic fenestration and referred to our unit after cyst recurrence.
      RESULTS: In all cases, the pathology report was consistent with liver
      cystadenomas. The postoperative course was uneventful and the median hospital
      stay was 8 days (range 5-12 days). In a median 18-month follow-up (range 2-40
      months), all patients are alive and free of recurrence. CONCLUSION: Liver
      cystadenomas can be easily misdiagnosed with other hepatic cystic lesions. An
      aggressive surgical approach is recommended, due to their malignant potential and
      high recurrence rate after fenestration.

PMID- 18090984
TI  - Is endoscopic sphincterotomy avoidable in patients with sphincter of Oddi
      dysfunction?
AB  - AIM: Endoscopic sphincterotomy is an efficient means of treating sphincter of
      Oddi dysfunction (SOD), but it is associated with a morbidity rate of 20%. The
      aim of this study was to assess how frequently endoscopic sphincterotomy was
      performed to treat SOD in a group of patients with a 1-year history of medical
      management. METHODS: A total of 59 patients, who had been cholecystectomized 9.3
      years previously on average, were included in this study and they all underwent
      biliary scintigraphy. Medical treatment was prescribed for 1 year. Endoscopic
      sphincterotomy was proposed for patients whose medical treatment had been
      unsuccessful. RESULTS: Eleven patients were rated group 1 on the Milwaukee
      classification scale, 34 group 2 and 14 group 3. The hile-duodenum transit time
      (HDTT) was lengthened in 32 patients. The medical treatment was efficient or
      fairly efficient in 45% of the group 1 patients, 67% of the group 2 patients, and
      71.4% of the group 3 patients (P=0.29). Only 14 patients out of the 21 whose
      medical treatment was unsuccessful agreed to undergo endoscopic sphincterotomy.
      HDTT was lengthened in 11 of the 14 patients undergoing endoscopic sphincterotomy
      and in 21 of the 45 non-endoscopic sphincterotomy patients (P=0.03). Twelve of
      the 14 patients who underwent endoscopic sphincterotomy were cured. CONCLUSION:
      In this prospective series of patients with a 1-year history of medical
      management, only 23% of the patients with suspected SOD underwent endoscopic
      sphincterotomy although 54% had an abnormally long HDTT.

PMID- 18090985
TI  - DNA damage in peripheral blood lymphocytes of patients with cirrhosis related to
      alcohol abuse or to hepatitis B and C viruses.
AB  - BACKGROUND: Both alcohol abuse and hepatitis B or C virus infections are
      implicated in the development of hepatocellular carcinoma, but it is still
      controversial whether the pathogenetic mechanism is epigenetic or genotoxic. AIM:
      Considering that alcohol promotes the generation of reactive oxygen species and
      both viruses infect peripheral lymphocytes, in this study we investigated the
      occurrence of DNA fragmentation in peripheral blood lymphocytes from patients
      with alcoholic cirrhosis and from patients with cirrhosis related to B and C
      viruses, and analyzed the correlation between the degree of DNA fragmentation and
      the Child-Pugh score used to assess the degree of hepatic insufficiency. METHODS:
      The study population consisted of two groups: group I involved 12 patients with
      alcoholic cirrhosis; group II involved 25 patients with hepatic B virus or
      hepatic C virus cirrhosis. The control group involved 20 healthy individuals. The
      degree of DNA fragmentation in peripheral blood lymphocytes was determined with
      the alkaline Comet assay that provides two indexes of the frequency of DNA single
      strand breaks and alkali-labile sites, the tail length and the tail moment.
      RESULTS: Mean values of both tail length and tail moment were significantly
      increased (P<0.001) in lymphocytes from 12 patients with alcoholic cirrhosis and
      in lymphocytes from 25 patients with HBV or HCV cirrhosis, as compared with
      average tail length and tail moment values of lymphocytes from 20 healthy
      individuals. A significant positive correlation was found to exist between the
      degree of DNA fragmentation present in lymphocytes of each of the 37 patients
      with alcoholic or viral cirrhosis and the corresponding value of the Child-Pugh
      score. CONCLUSION: The occurrence of DNA fragmentation in peripheral blood
      lymphocytes reflects a direct genotoxic effect of either alcohol or HBV and HCV
      and suggests that the same genotoxic effect may operate in the liver and
      contribute to hepatocarcinogenesis.

PMID- 18090986
TI  - Pneumocystis pneumonia: an opportunistic infection occurring in patients with
      severe alcoholic hepatitis.
AB  - BACKGROUND: Pneumocystis pneumonia usually occurs in immunosuppressed
      individuals, generally those with underlying T-lymphocyte disorders. Patients
      with alcoholic liver disease display immune responses consistent with those
      observed in immunocompromised individuals and alcohol is a potent
      immunosuppressor. Long-term corticotherapy represents a risk for Pneumocystis
      pneumonia. PATIENTS AND METHODS: From 1998 to 2006, seven patients hospitalized
      in our Liver Intensive Care Unit for severe alcoholic hepatitis had a diagnosis
      of Pneumocystis pneumonia. All had liver biopsies revealing histologic evidence
      of alcoholic hepatitis. The diagnosis of pneumocystosis was established by the
      detection in the bronchoalveolar lavage of the characteristic pathogen, with
      Giemsa staining or immunofluorescence assay, in addition to the presence of
      clinical and radiological signs of pneumopathy. RESULTS: All seven patients had a
      Maddrey score higher than 32. Six patients received corticotherapy for alcoholic
      hepatitis treatment before the diagnosis of Pneumocystis pneumonia. All patients
      developed acute respiratory distress syndrome and needed mechanical ventilation.
      In three patients, the test for cytomegalovirus was also positive in the
      bronchoalveolar lavage. All seven patients died in spite of receiving appropriate
      treatment. CONCLUSION: Chronic alcoholism and alcoholic liver disease are both
      associated with an important degree of immunosuppression. Corticotherapy, even
      for a short period, may aggravate this immunodeficiency and predispose these
      patients to severe opportunistic infections.

PMID- 18090987
TI  - Hepatitis C virus transmission among oral crack users: viral detection on crack
      paraphernalia.
AB  - OBJECTIVE: Epidemiological studies present oral crack use as a potential
      independent risk factor for hepatitis C virus (HCV) status, yet actual HCV
      transmission pathways via crack use have not been evidenced. To this end, this
      exploratory study sought to detect HCV on crack-use paraphernalia used by street
      crack users. METHODS: Crack-use paraphernalia within 60 min of use was collected
      from 51 (N) street-crack users. HCV RNA detection was conducted through eluate
      sampling and manual RNA extraction. Participants provided a saliva sample to test
      for HCV antibody, and had a digital photograph taken of their oral cavities, to
      assess the presence of oral sores as a possible risk factor for oral HCV
      transmission. RESULTS: About 43.1% (n=22) of the study participants were HCV
      antibody positive. One (2.0%) of the 51 pipes tested positive. A minority of the
      participants presented oral sores. The pipe on which HCV was detected was made
      from a glass stem; its owner was HCV-antibody positive, and there was full rater
      agreement on the presence of oral sores in the pipe owner's oral cavity.
      CONCLUSIONS: HCV transmission from an infected host onto paraphernalia as a
      precondition of HCV host-to-host transmission via shared crack paraphernalia use
      seems possible, with oral sores and paraphernalia condition constituting possible
      risk modifiers. Larger-scale studies with crack users are needed to corroborate
      our findings.

PMID- 18090988
TI  - Identification of Helicobacter species by 16S rDNA PCR and sequence analysis in
      human liver samples from patients with various etiologies of benign liver
      diseases.
AB  - BACKGROUND/AIMS: Several reports indicated an increased prevalence of the
      Helicobacter species in hepatocellular cancer tissue and in liver samples
      infected with hepatitis viruses. The frequency of Helicobacter spp. in benign
      liver diseases was, however, not thoroughly investigated. METHODS: Seventy-five
      consecutive patients with suspected liver disease were enrolled. The indications
      were hepatitis B virus (n=30), C virus (n=8), B and C dual infection (n=1),
      nonalcoholic steatohepatitis (n=27), autoimmune hepatitis (n=3), primary biliary
      cirrhosis (n=1) and idiopathic elevation of liver enzymes (n=5). PCR detection of
      16S recombinant RNA gene of Helicobacter spp. was performed on liver samples. PCR
      products of positive samples were further identified by DNA sequencing. The
      patients also had upper gastrointestinal endoscopy and gastric biopsy for the
      detection of H. pylori using histopathology and PCR. RESULTS: Helicobacter spp.
      DNA was detected in two out of 75 liver biopsy samples (2.6%), which were typed
      as H. pylori by DNA sequencing. One of these patients had chronic hepatitis C
      infection (man, 51 years old) and the other had nonalcoholic steatohepatitis
      (woman, 44 years old). Fifty-two out of 75 of the patients (69.3%) had H. pylori
      infection in their stomachs. CONCLUSION: We have found that H. pylori infection
      is much less prevalent in benign liver diseases. The presence of H. pylori in
      nonalcoholic steatohepatitis (NASH) patients is a novel finding and this finding
      should be confirmed in a larger series.

PMID- 18090989
TI  - Diverse effects of the CARD15 and IBD5 loci on clinical phenotype in 630 patients
      with Crohn's disease.
AB  - OBJECTIVES: Genetic variants at the CARD15 and IBD5 loci are strongly associated
      with Crohn's disease (CD), but evidence of the effect of these variants on the
      clinical expression of CD is conflicting and has often been hampered by small
      sample sizes. We studied 630 well-characterized patients to clarify the
      genotype/phenotype relationship in CD. METHODS: Patients and healthy controls
      were genotyped for three common mutations in CARD15 and a marker of the IBD5 risk
      haplotype. Allele frequencies were compared between phenotypic subgroups using
      chi2 or Fisher's exact tests. Genotype/phenotype analysis was carried out using
      multinomial logistic regression modelling allowing for adjustment for correlated
      or confounding factors. RESULTS: The mean age at diagnosis was significantly
      lower in carriers of the CARD15 or IBD5 risk alleles. After correction for age
      and smoking, CARD15 mutations were strongly associated with both ileal disease
      (P=8.8 x 10(-6)) and stenotic disease (P=0.003), but the association with
      stenotic disease appeared to be due to a confounding effect with ileal disease.
      CARD15 mutations were also associated with the presence of granulomas (P=5.7 x
      10(-5)), which remained significant after adjustment for age at diagnosis and
      disease location (P=0.0047). The IBD5 risk haplotype frequency was significantly
      elevated in cases with perianal disease (P=0.028) and axial spondyloarthropathy
      (P=0.012). CONCLUSION: Genetic variants at the CARD15 and IBD5 loci have diverse
      effects on clinical expression in CD. CARD15 mutations are significantly
      correlated with the presence of granulomas.

PMID- 18090990
TI  - Ulcerative colitis and irritable bowel syndrome: relationships with quality of
      life.
AB  - OBJECTIVES: Quality of life is reduced in inflammatory bowel disease. Irritable
      bowel syndrome (IBS)-like symptoms seem to be common in inflammatory bowel
      disease patients during the remission phase. We aimed to (i) assess the
      prevalence of IBS-like symptoms in ulcerative colitis (UC) patients during the
      remission phase and (ii) evaluate the impact of IBS symptoms on health-related
      quality of life (HRQOL) of UC patients in remission compared with the HRQOL of
      those in the active phase. METHODS: Ninety-five patients with UC (45 patients in
      the active phase and 50 in remission for at least 12 months) and 100 selected
      controls (recruited from among those who visited the orthopedic minor trauma
      outpatient clinic during 2004-2005) completed questionnaires to evaluate IBS-like
      symptoms according to ROME II criteria: the influence of these symptoms on the
      HRQOL of UC patients in remission was compared with that on the HRQOL of those in
      the active phase. Chi square and nonparametric tests were used. RESULTS: The
      prevalence of IBS-like symptoms in UC patients in remission and controls were 46
      and 13%, respectively (P<0.001). HRQOL seemed to be significantly reduced in both
      active UC patients and UC patients in remission with IBS, compared with UC
      patients in remission without IBS and with controls (P<0.001). In active UC
      patients, the mean scores for most elements (as measured by SF36) were
      considerably lower than for UC patients in remission (P<0.05). CONCLUSION: The
      prevalence of IBS-like symptoms in UC patients in remission is about three times
      higher than in controls, and these patients have impaired HRQOL comparable with
      that of UC patients in the active phase.

PMID- 18090991
TI  - Safety and utility of oesophago-gastro-duodenoscopy in acute myocardial
      infarction.
AB  - AIM: To study the safety and utility of performing an oesophago-gastro
      duodenoscopy (EGD) in the setting of an acute myocardial infarction (AMI).
      METHODS: Case records of all patients who underwent an EGD for various
      indications within 4 weeks of an AMI between January 2001 and April 2006 were
      analyzed. Demographic data, indications for endoscopy, outcomes and complications
      were noted. Main outcome measures included safety and utility of endoscopy in
      AMI. RESULTS: A total of 87 EGDs were performed on 85 patients with AMI. Seventy
      (83%) patients had a non-ST elevation MI, whereas 15 (17%) had ST elevation MI.
      Mean time between EGD and AMI was 6+/-1.8 days. Indications for EGD were
      hematemesis and/or melena on presentation in 38 (44.7%), hematemesis and/or
      melena post anticoagulation in 27 (31.8%). EGD findings were gastric
      ulcer/erosions in 30 (34%), oesophago-gastric varices in 20 (22%), erosive
      oesophagitis in 17 (20%) and duodenal ulcer in 11 (13%). Diagnostic yield of EGD
      was 88%. Endoscopic interventions were performed in 26 (30%) patients with high
      risk of bleeding lesion. There were no EGD-related mortality, whereas 14 patients
      re-bled. A total of 21 patients died, including 7/14 (50%) who re-bled, compared
      with 14/71 (19%) without rebleed (P=0.008). There were no EGD-related deaths.
      Fourteen patients were on mechanical ventilation and 6/14 (43%) of these died as
      compared with 15/88 (17%) who were not ventilated (P=0.027). CONCLUSION: EGD is
      safe and useful in diagnosis and management of gastrointestinal hemorrhage in
      patients with AMI, and allows decisions about anticoagulation. Re-bleed and need
      for mechanical ventilation predicts poor outcome in these patients.

PMID- 18090992
TI  - Constipation during pregnancy: a longitudinal survey based on self-reported
      symptoms and the Rome II criteria.
AB  - An increase in the prevalence of constipation during pregnancy has been suggested
      to occur. We designed a prospective study to evaluate the prevalence of
      constipation during pregnancy and puerperium, to investigate possible
      associations with eating habits and lifestyle, and to evaluate the frequency of
      laxative use. A structured questionnaire was developed addressing demographics,
      obstetric characteristics, lifestyle, eating habits, variables required for the
      diagnosis of constipation, and laxative use to evaluate the prevalence of
      constipation during pregnancy and puerperium. The questionnaire was administered
      in the obstetric clinic in the first trimester of pregnancy, and by telephone in
      the second and third trimesters, and in the puerperal period. The prevalence of
      self-reported constipation in these time periods was 45.4, 37.1, 39.4, and 41.8%,
      respectively. Prevalence defined by the Rome II criteria for the same time
      periods was 29.6, 19, 21.8, and 24.7%. These values were similar to the data
      previously reported for the female population. Agreement between the self
      reported and Rome II results was moderate. The self-reported criterion showed
      high sensitivity in all time periods, using the Rome II criterion as gold
      standard. No factor was associated with variations in the prevalence of
      constipation during pregnancy, though an increase was recorded in the consumption
      of fruit, vegetables, fiber, and water. The prevalence of constipation during
      pregnancy and puerperium is similar to that recorded among the female population
      from the same geographic area.

PMID- 18090993
TI  - Jejunal tonometry for the diagnosis of gastrointestinal ischemia. Feasibility,
      normal values and comparison of jejunal with gastric tonometry exercise testing.
AB  - BACKGROUND AND AIM: In most patients with chronic splanchnic syndrome the celiac
      artery is involved, enabling the use of gastric exercise tonometry as a
      diagnostic function test. In this study, we investigated the feasibility of
      combining gastric and jejunal exercise tonometry and determined the normal
      values. We investigated the potential diagnostic value of combining gastric with
      jejunal exercise tonometry. MATERIALS AND METHOD: Between 1998 and 2000, combined
      gastric and jejunal exercise tonometry tests were performed in a healthy
      volunteer and in patients suspected of chronic gastrointestinal ischemia. Using
      automated air tonometry, gastric (PgCO2) and jejunal PCO2 (PjCO2) were measured
      before, during and after 10-min of exercise. Luminal-arterial PCO2 gradients
      (DeltagPCO2 respectively DeltajPCO2) were calculated. In the patient cohort,
      final diagnosis of chronic ischemia was made by our institutional
      multidisciplinary working group on gastrointestinal ischemia. RESULTS: Jejunal
      tonometry was possible in 25 of 27 participants. The healthy volunteer was tested
      twice, yielding a total of 26 combined tests. Mean normal basal PjCO2 was 0.9 kPa
      higher than PgCO2. The calculated upper threshold (mean+2SD) of normal DeltajPCO2
      was 1.4 kPa. In five of eight patients with chronic gastrointestinal ischemia
      gastric exercise tonometry was abnormal, in one, both gastric and jejunal
      tonometry were abnormal, in two only jejunal exercise tonometry was abnormal.
      CONCLUSION: Combined gastric and jejunal exercise tonometry is a feasible
      procedure that is relatively easy to perform. On the basis of this pilot study,
      jejunal tonometry seems to have a small additional value in the diagnosis of
      chronic gastrointestinal ischemia.

PMID- 18090994
TI  - Thiopurine-methyltransferase and inosine triphosphate pyrophosphatase
      polymorphism in a liver transplant recipient developing nodular regenerative
      hyperplasia on low-dose azathioprine.
AB  - The enzymes thiopurine-methyltransferase (TPMT) and inosine triphosphate
      pyrophosphatase (ITPA) are involved in thiopurine metabolism. We describe a liver
      transplant recipient who presented with liver enzyme abnormalities after 78
      months of low-dose azathioprine (AZA) therapy (less than 1 mg/kg). No underlying
      etiology of these abnormalities was identified after extensive analysis including
      repeated liver biopsy. Fifteen years after transplantation, the patient presented
      with variceal bleeding, liver biopsy showed nodular regenerative hyperplasia
      (NRH). TPMT*3C genotype was found in the patient's lymphocytes and heterozygous
      ITPA (94C>A) genotype was found in both patient and donor liver. These findings
      further emphasize the importance of pharmacogenetics in predicting NRH and other
      adverse events during AZA therapy. Furthermore, a high index of suspicion with
      early detection of NRH is crucial, as improvement seems only to occur in patients
      with compensated liver disease. Liver biopsy and discontinuation of AZA are
      recommended in case of liver enzyme abnormalities or signs of portal
      hypertension.

PMID- 18090995
TI  - Nosocomial transmission of hepatitis C virus during contrast-enhanced computed
      tomography scanning.
AB  - We have investigated two cases of acute hepatitis C that occurred in patients who
      underwent digestive endoscopy and contrast-enhanced computed tomography (CT)
      scanning at two different centers. Investigations to identify the sources of
      infection included an on-site review of diagnostic procedures, interview of the
      involved healthcare staff, serological testing of the patients who underwent the
      procedures before and after the index cases and a molecular analysis of viral
      isolates from the patients and from potential viremic sources. In both cases, the
      epidemiological investigation identified a chronic hepatitis C virus (HCV)
      carrier who had been subjected to CT-scanning immediately before the index
      patient. Genetic distance and molecular phylogenetic analyzes of HCV sequences
      showed a close relationship between the isolates from these carriers and those
      from the acute-hepatitis patients, strongly suggesting that patient-to-patient
      transmission had occurred during CT. This is the first report describing two well
      documented cases of HCV nosocomial patient-to-patient transmission during
      contrast-enhanced CT scanning.

PMID- 18090996
TI  - Autoimmune hepatitis associated with Kikuchi-Fujimoto's disease.
AB  - We describe a 20-year-old woman with autoimmune hepatitis (AIH) with cirrhosis
      who developed Kikuchi-Fujimoto's disease (KFD) and de novo minor features of
      systemic lupus erythematosus (SLE). This is the first report of a patient with
      histologically confirmed AIH developing KFD (histiocytic necrotizing
      lymphadenitis). One previous case described KFD after AIH (diagnosed clinically
      but without biopsy). KFD is a rare condition of unknown aetiology, first
      described in 1972, characterized by fever and cervical adenopathy and has a self
      limiting course. KFD is associated with SLE, and SLE in turn can be associated
      with abnormal liver function tests, which in a minority of cases may be due to
      AIH. The association of AIH, KFD, and SLE in our patient suggests an autoimmune
      pathogenesis of KFD.

PMID- 18090997
TI  - Fatal hemobilia resulting from an iatrogenic arteriobiliary fistula as a rare
      complication of transjugular liver biopsy.
AB  - Transjugular liver biopsy is an important tool for diagnosing and/or staging of
      advanced liver disease. This procedure is considered safe even in the presence of
      severe coagulopathy, although rare fatal complications have been described. We
      herein report the first case of fatal hemobilia after transjugular liver biopsy.
      A patient with alcoholic liver cirrhosis developed hematemesis 1 day after
      transjugular liver biopsy. Upper gastrointestinal endoscopy revealed bleeding
      from the papilla of Vater. Despite early intervention by angiography and
      embolization of an arteriobiliary fistula, the patient deteriorated and
      ultimately died due to multiorgan failure.

PMID- 18090998
TI  - A phase II study of tegafur plus uracil or tegafur alone for the treatment of
      advanced hepatocellular carcinoma.

PMID- 18090999
TI  - Nested randomized trials in large cohorts and biobanks: studying the health
      effects of lifestyle factors.
AB  - Most diseases are likely to result largely from the interplay of lifestyle and
      genetic factors. However, both observational studies and randomized trials have
      faced major limitations in trying to address the impact of lifestyle on health.
      As large cohorts and biobanks are being developed, we need to find novel,
      efficient ways to address the effects of lifestyle interventions. We propose that
      this could be done using multiple lifestyle factorial experimental designs that
      combine characteristics of randomized trials and epidemiologic studies.
      Randomized trials of simple lifestyle interventions can be nested within large
      cohorts linked to reliable registries of outcomes. Participants can choose from a
      long list of simple lifestyle randomization options and many interventions may be
      tested concurrently with factorial randomization. Participants can tailor their
      own personal trial choosing several items among long laundry lists of
      randomization options. Participants are citizen-scientists rather than passive
      subjects and this may be attractive in modern societies of health-conscious
      people. These trials can use the existing machinery of the cohort for data
      collection and outcome linkage at no or minimal additional cost. We discuss a
      number of issues on the implementation of multiple lifestyle factorial
      experimental designs, as compared with the usual observational studies and
      randomized trials. These include participation, the number of allowed
      randomizations per participant, compliance/adherence, power, false-negatives,
      false-positives, composite lifestyle effects, selection of outcomes, follow-up
      and monitoring, masking and allocation concealment, age of participants,
      confounding, and cost. The aim should be to combine carefully the strengths of
      both observational epidemiology and randomized research without compounding their
      limitations.

PMID- 18091000
TI  - Adjustment for multiple cardiovascular risk factors using a summary risk score.
AB  - BACKGROUND: To simultaneously adjust for confounding by multiple cardiovascular
      risk factors, recently published pharmacoepidemiologic studies have used an index
      of risk of cardiovascular disease (a cardiovascular risk score). This summary
      measure is a multivariate confounder score created from regression models
      relating these risk factors to the outcome. The score is then used in regression
      models to adjust for potential confounding of the exposure of interest. Although
      this summary score has a number of advantages, there is concern that it may
      result in underestimation of the standard error of the exposure estimate and thus
      inflate the number of statistically significant results. METHODS: We conducted
      simulation studies comparing regression models adjusting for all risk factors
      directly to models using this summary risk score for large cohort studies.
      RESULTS: Results indicated that, as long as there was not a high degree of
      intercorrelation between the potential confounders and the exposure, estimated
      standard errors from the regression models using this summary risk score
      approximate their empirical standard errors well and are similar to the standard
      errors from the regression models directly adjusting for all risk factors.
      CONCLUSIONS: Based on these simulation results, using this summary risk score can
      be a reasonable approach for summarizing many risk factors in large cohort
      studies.

PMID- 18091001
TI  - Air pollution and heart rate variability: effect modification by chronic lead
      exposure.
AB  - BACKGROUND: Outdoor air pollution and lead exposure can disturb cardiac autonomic
      function, but the effects of both these exposures together have not been studied.
      METHODS: We examined whether higher cumulative lead exposures, as measured by
      bone lead, modified cross-sectional associations between air pollution and heart
      rate variability among 384 elderly men from the Normative Aging Study. We used
      linear regression, controlling for clinical, demographic, and environmental
      covariates. RESULTS: We found graded, significant reductions in both high
      frequency and low-frequency powers of heart rate variability in relation to ozone
      and sulfate across the quartiles of tibia lead. Interquartile range increases in
      ozone and sulfate were associated respectively, with 38% decrease (95% confidence
      interval = -54.6% to -14.9%) and 22% decrease (-40.4% to 1.6%) in high frequency,
      and 38% decrease (-51.9% to -20.4%) and 12% decrease (-28.6% to 9.3%) in low
      frequency, in the highest quartile of tibia lead after controlling for potential
      confounders. We observed similar but weaker effect modification by tibia lead
      adjusted for education and cumulative traffic (residuals of the regression of
      tibia lead on education and cumulative traffic). Patella lead modified only the
      ozone effect on heart rate variability. CONCLUSIONS: People with long-term
      exposure to higher levels of lead may be more sensitive to cardiac autonomic
      dysfunction on high air pollution days. Efforts to understand how environmental
      exposures affect the health of an aging population should consider both current
      levels of pollution and history of lead exposure as susceptibility factors.

PMID- 18091002
TI  - Neighborhood resources for physical activity and healthy foods and their
      association with insulin resistance.
AB  - OBJECTIVE: : Little is known about the influence of the built environment, and in
      particular neighborhood resources, on health. We hypothesized that neighborhood
      resources for physical activity and healthy foods are associated with insulin
      resistance. METHODS: : Person-level data (n = 2026) came from 3 sites of The
      Multi-Ethnic Study of Atherosclerosis, a study of adults aged 45-84 years. Area
      level data were derived from a population-based residential survey. The
      homeostasis model assessment index was used as an insulin resistance measure
      among persons not treated for diabetes. We used linear regression to estimate
      associations between area features and insulin resistance. RESULTS: : Greater
      neighborhood physical activity resources consistently were associated with lower
      insulin resistance. Adjusted for age, sex, family history of diabetes,
      race/ethnicity, income and education, insulin resistance was reduced by 17% (95%
      confidence interval = -31% to -1%) for an increase from the 10th to 90th
      percentiles of resources. Greater healthy food resources were also inversely
      related to insulin resistance, although the association was not robust to
      adjustment for race/ethnicity. Analyses including diet, physical activity, and
      body mass index suggested that these variables partly mediated observed
      associations. Results were similar when impaired fasting glucose/diabetes was
      considered as the outcome variable. CONCLUSION: : Diabetes prevention efforts may
      need to consider features of residential environment.

PMID- 18091003
TI  - Longitudinal determinants of posttraumatic stress in a population-based cohort
      study.
AB  - BACKGROUND: Posttraumatic stress disorder is a prevalent and disabling
      psychologic pathology. Longitudinal research on the predictors of posttraumatic
      stress symptomatology is limited. METHODS: We recruited 2752 participants to a
      prospective, population-based cohort study by conducting a telephone survey of
      adult residents of the New York City metropolitan area in 2002; participants
      completed 3 follow-up interviews over a 30-month period. Censoring weights were
      estimated to account for potential bias. We used generalized estimating equation
      logistic regression models with bootstrapped confidence intervals to assess the
      predictors of posttraumatic stress over time in multivariable models. RESULTS:
      Predictors of posttraumatic stress over time included ongoing stressors (odds
      ratio [OR] = 1.91 per 1 unit increase in number of stressors, [95% confidence
      interval = 1.55-2.36]) and traumatic events (OR = 1.92 per 1 unit increase in
      number of traumatic events [CI = 1.71-2.22]), social support (compared with high
      levels, OR = 1.71 for medium [1.09-2.52]; OR = 1.57 for low [1.08-2.35]), low
      income (OR = 0.87 per $10,000 increase [0.81-0.92]), female sex (1.60 [1.11
      2.23]), and Latino ethnicity (compared with white, OR = 1.74 [1.05-2.97]).
      CONCLUSIONS: These findings suggest that ongoing stressors play a central role in
      explaining the trajectory of posttraumatic stress over time, and that factors
      beyond the experience of stressors and traumas may account for sex and ethnic
      differences in posttraumatic stress risk. Interventions that focus on reducing
      ongoing adversity may help mitigate the consequences of traumatic events.

PMID- 18091004
TI  - Caffeine and miscarriage risk.
AB  - BACKGROUND: Coffee and caffeine have been inconsistently found to be associated
      with increased risk of clinical miscarriage-a potentially important association
      given the high prevalence of exposure. METHODS: Women were recruited before or
      early in pregnancy and interviewed regarding sources of caffeine, including
      assessment of changes over the perinatal period. We identified 2407 clinically
      recognized pregnancies resulting in 258 pregnancy losses. We examined the
      relationship of coffee and caffeine intake with clinically-recognized pregnancy
      loss prior to 20 weeks' completed gestation, using a discrete-time continuation
      ratio logistic survival model. RESULTS: Coffee and caffeine consumption at all 3
      time points were unrelated to total miscarriage risk and the risk of loss after
      the interview. Reported exposure at the time of the interview was associated with
      increased risk among those with losses before the interview. CONCLUSIONS: There
      is little indication of possible harmful effects of caffeine on miscarriage risk
      within the range of coffee and caffeine consumption reported, with a suggested
      reporting bias among women with losses before the interview. The results may
      reflect exposure misclassification and unmeasured heterogeneity of pregnancy
      losses.

PMID- 18091005
TI  - Residential outdoor air pollution and lung function in schoolchildren.
AB  - BACKGROUND: Long-term exposure to outdoor air pollution has typically been
      estimated on the aggregate level, and more individual measures of exposure are
      needed. We investigated the associations with lung function of residential
      outdoor air pollution in early life, total lifetime, and days before lung
      function test. METHODS: In 2001-2002, spirometry was performed in 2307 9- and 10
      year-old children who had lived in Oslo, Norway, since birth. Outdoor air
      pollution exposure for each child was assessed by the EPISODE dispersion model,
      calculating hourly concentrations of nitrogen dioxide (NO2), particulate matter
      (PM) with aerodynamic diameter less than 10 microm (PM10) and 2.5 microm (PM2.5).
      We applied linear regression analysis stratified by sex. RESULTS: Early and
      lifetime exposures to outdoor air pollution were associated with reduced peak
      expiratory flow and reduced forced expiratory flow at 25% and 50% of forced vital
      capacity, especially in girls. One interquartile increase of lifetime exposure to
      NO2, PM10, and PM2.5 was associated with change in adjusted peak respiratory flow
      of, respectively, -79 mL/s (95% confidence interval = -128 to -31), -66 mL/s (
      110 to -23), and -58 mL/s (-94 to -21). We also found short-term effects of NO2
      that became stronger with increasing time lags, but no short-term effects of PM.
      When we included short- and long-term NO2 exposures simultaneously, only the long
      term effect remained. We found no effect on forced volumes. Adjusting for a
      contextual socioeconomic factor diminished the associations. CONCLUSIONS: Short-
      and long-term residential exposures to traffic-related pollutants in Oslo were
      associated with reduced peak expiratory flow and forced expiratory flow at 25%
      and 50% in 9- to 10-year-old children, especially in girls, with weaker
      associations after adjusting for a contextual socioeconomic factor.

PMID- 18091006
TI  - Physical activity in the United States measured by accelerometer.
AB  - PURPOSE: To describe physical activity levels of children (6-11 yr), adolescents
      (12-19 yr), and adults (20+ yr), using objective data obtained with
      accelerometers from a representative sample of the U.S. population. METHODS:
      These results were obtained from the 2003-2004 National Health and Nutritional
      Examination Survey (NHANES), a cross-sectional study of a complex, multistage
      probability sample of the civilian, noninstitutionalized U.S. population in the
      United States. Data are described from 6329 participants who provided at least 1
      d of accelerometer data and from 4867 participants who provided four or more days
      of accelerometer data. RESULTS: Males are more physically active than females.
      Physical activity declines dramatically across age groups between childhood and
      adolescence and continues to decline with age. For example, 42% of children ages
      6-11 yr obtain the recommended 60 min x d(-1) of physical activity, whereas only
      8% of adolescents achieve this goal. Among adults, adherence to the
      recommendation to obtain 30 min x d(-1) of physical activity is less than 5%.
      CONCLUSIONS: Objective and subjective measures of physical activity give
      qualitatively similar results regarding gender and age patterns of activity.
      However, adherence to physical activity recommendations according to
      accelerometer-measured activity is substantially lower than according to self
      report. Great care must be taken when interpreting self-reported physical
      activity in clinical practice, public health program design and evaluation, and
      epidemiological research.

PMID- 18091007
TI  - Maintenance of physical activity in breast cancer survivors after a randomized
      trial.
AB  - PURPOSE: The purpose of this study was to examine the longer-term effects of
      pedometers and print materials on changes in physical activity (PA) and health
      related quality of life (HRQoL) in breast cancer survivors who participated in a
      3-month behavior change intervention. METHODS: Breast cancer survivors (N = 377)
      were randomly assigned to receive either (a) a standard public health
      recommendation for PA (SR), (b) previously developed breast cancer-specific PA
      print materials (PM), (c) a step pedometer (PED), or (d) a combination of the two
      (COM). The primary endpoint was self-reported moderate/vigorous PA minutes per
      week at 6-month follow-up after the initial 3-month intervention period. RESULTS:
      Seventy-one percent (266/377) of participants completed the 6-month follow-up
      assessment. According to intention-to-treat linear mixed-model analyses, self
      reported moderate to vigorous PA increased by 9 min x wk(-1) in the SR group
      compared with 39 min x wk(-1) in the PM group (mean difference = 30 min x wk(-1);
      95% CI = -44 to 104; P = 0.425), 69 min x wk(-1) in the PED group (mean
      difference = 60 min x wk(-1); 95% CI = -13 to 132; P = 0.107), and 56 min x wk(
      1) in the COM group (mean difference = 47 min x wk(-1); 95% CI = -26 to 119; P =
      0.210). The same pattern was observed for self-reported, brisk walking. No
      differences were found for HRQoL or fatigue. CONCLUSION(S): Breast cancer
      specific PM and PED did not maintain significantly higher PA or HRQoL at 6-month
      follow-up in breast cancer survivors, but the magnitude of the effect on PA (30
      60 min x wk(-1)) was consistent with the immediate postintervention effect
      observed at the 3-month postintervention time point. Issues of power resulting
      from additional loss to follow-up may account for the failure to achieve
      statistical significance. Additional research with larger sample sizes and more
      complete follow-up is warranted.

PMID- 18091008
TI  - The relation of aerobic fitness to stroop task performance in preadolescent
      children.
AB  - PURPOSE: We investigated the relation between aerobic fitness and interference
      control--one component of executive control--in 74 children between 7 and 12 yr
      of age. METHOD: Participants completed a paper-and-pencil version of the Stroop
      color-word task and the FITNESSGRAM, a valid and reliable test measuring
      different components of physical fitness (i.e., aerobic, muscle, and body
      composition). During each condition of the Stroop task (word, color, color-word),
      participants were instructed to read aloud as many items as possible in 45 s.
      Data were also collected on IQ and personal and health demographics to account
      for other factors influencing the relationship between fitness and executive
      function. RESULTS: Older children and those with higher IQ responded to more
      items correctly during each of the three conditions. Greater aerobic fitness was
      also associated with better performance on each of the three Stroop conditions
      independently of the other variables. CONCLUSION: These findings suggest that
      increased levels of fitness may be beneficial to cognition during preadolescent
      development.

PMID- 18091009
TI  - Pharmacological and psychological effects of caffeine ingestion in 40-km cycling
      performance.
AB  - The ergogenic effects of caffeine are well documented. Research has yet to
      examine any psychological contribution to this effect. AIM: To explore the
      psychological and pharmacological effects of caffeine in laboratory cycling
      performance. METHOD: Fourteen male competitive cyclists performed 14 40-km time
      trials (eight experimental interspersed with six baseline). The experimental
      phase consisted of two trials for each of four experimental conditions: informed
      caffeine/received caffeine, informed no treatment/received caffeine, informed
      caffeine/received placebo, and informed no treatment/received no treatment.
      Conditions were nonrandomized. ANOVA was used to estimate main effects and
      interactions for mean values of power, heart rate, blood lactate, and maximal
      oxygen uptake. Probabilistic inferences for mean power were based on a smallest
      worthwhile change of 1.5%. RESULTS: Relative to baseline, a very likely
      beneficial main effect of receiving caffeine (3.5%; 95% confidence interval 1.5
      to 5.5%), and a possibly beneficial main effect of being informed of caffeine
      (0.7%; -0.7 to 2.1%) were observed. A substantial interaction between belief and
      pharmacology indicated that caffeine exerted a greater effect on performance in
      conditions when subjects were informed that they had not ingested it, whereas
      belief exerted a greater influence on performance in the absence of caffeine
      (2.6%; -0.7 to 5.9%). A possibly harmful negative placebo (nocebo) effect was
      observed when subjects were correctly informed that they had ingested no caffeine
      (-1.9%; -4.1 to 0.3%). No clinically significant changes relative to baseline
      were observed in mean heart rate. Clear and substantial increases in blood
      lactate were evident after receipt of caffeine. Data for mean oxygen uptake were
      unclear. CONCLUSION: Our data support the ergogenic efficacy of caffeine but
      suggest that both positive and negative expectations impact performance.

PMID- 18091010
TI  - Dose response of inhaled salbutamol on exercise performance and urine
      concentrations.
AB  - PURPOSE: This study determined the dose-response effects of inhaled salbutamol
      (SAL) on time-trial performance and urine concentrations of SAL (cSAL). METHODS:
      Nonasthmatic, trained male cyclists and triathletes (N = 37) were studied. Day 1
      consisted of screening for airway hyperresponsiveness, using a eucapnic voluntary
      hyperpnea test (EVH), followed by an incremental exercise test to determine V O
      2max and peak power (P max). On days 2-5, athletes performed a 20-km time trial
      15 min after inhalation (PI) of placebo, 200 microg (D2), 400 microg (D4), or 800
      microg (D8) of SAL. At 60 min PI, urine samples were provided. All conditions
      were randomized and double blinded, with repeated-measures ANOVA used to
      determine effects of dose. Post hoc analysis was done with Tukey's HSD test.
      RESULTS: Seven subjects had positive responses to the EVH test, resulting in a
      19% incidence within this sample; they were excluded from further participation
      in this study. The remaining subjects (N = 30) had a V O 2max of 67.1 (4.3) mL x
      kg(-1) x min(-1) and Pmax of 457 (31) W (W). There was no effect of dose on
      completion time (P > 0.05), mean power (P > 0.05), or mean heart rate (P > 0.05).
      Similarly, SAL had no effect on any metabolic or ventilatory parameters (P >
      0.05). Urine cSAL increased with dose and was highly variable, with the peak
      value observed being 831 ng x mL(-1) after a dose of 800 microg. Moderate but
      significant correlations were noted between cSAL and urine specific gravity at
      higher doses (D4, r = 0.42; D8, r = 0.37). CONCLUSIONS: These findings suggest
      that inhaled SAL does not enhance time-trial performance, regardless of dose, and
      that urine cSAL after exercise is related to dose, demonstrates high variability,
      and is partially related to hydration status.

PMID- 18091011
TI  - Seven intermittent exposures to altitude improves exercise performance at 4300 m.
AB  - PURPOSE: The purpose of this study was to determine whether seven intermittent
      altitude exposures (IAE), in combination with either rest or exercise training,
      improves time-trial exercise performance and induces physiologic adaptations
      consistent with chronic altitude adaptation at 4300 m. METHODS: Ten adult
      lowlanders (26 +/- 2 yr; 78 +/- 4 kg; means +/- SE) completed cycle endurance
      testing during an acute exposure to a 4300-m-altitude equivalent (446 mm Hg) once
      before (pre-IAE) and once after (post-IAE) 7 d of IAE (4h x d(-1), 5 d x wk(-1),
      4300 m). Cycle endurance testing consisted of two consecutive 15-min constant
      work rate exercise bouts followed immediately by a time-trial exercise
      performance test. During each IAE, five subjects performed exercise training, and
      the other group of five subjects rested. RESULTS: Both groups demonstrated
      similar improvements in time-trial cycle exercise performance and physiologic
      adaptations during constant-work rate exercise from pre-IAE to post-IAE. Thus,
      data from all subjects were combined. Seven days of IAE resulted in a 16%
      improvement (P < 0.05) in time-trial cycle exercise performance (min) from pre
      IAE (35 +/- 3) to post-IAE (29 +/- 2). During the two constant-work rate exercise
      bouts, there was an increase (P < 0.05) in exercise arterial O2 saturation (%)
      from pre-IAE (77 +/- 2; 75 +/- 1) to post-IAE (80 +/- 2; 79 +/- 1), a decrease (P
      < 0.05) in exercise heart rate (bpm) from pre-IAE (136 +/- 6; 162 +/- 5) to post
      IAE (116 +/- 6; 153 +/- 5), and a decrease (P < 0.05) in exercise ratings of
      perceived exertion from pre-IAE (10 +/- 1; 14+/- 1) to post-IAE (8 +/- 1; 11 +/-
      1). CONCLUSIONS: Our findings indicate that 7 d of IAE, in combination with
      either rest or exercise training, improves time-trial cycle exercise performance
      and induces physiologic adaptations during constant-work rate exercise consistent
      with chronic altitude adaptation at 4300 m.

PMID- 18091012
TI  - Vibration and stretching effects on flexibility and explosive strength in young
      gymnasts.
AB  - PURPOSE: Effects of simultaneous vibration-stretching on flexibility and
      explosive strength in competitive female gymnasts were examined. METHODS: Twenty
      two female athletes (age = 11.3 +/- 2.6 yr; body mass = 35.3 +/- 11.6 kg;
      competitive levels = 3-9) composed the simultaneous vibration-stretching (VS)
      group, which performed both tests. Flexibility testing control groups were
      stretching-only (SF) (N = 7) and vibration-only (VF) (N = 8). Explosive strength
      control groups were stretching-only (SES) (N = 8) and vibration-only (VES) (N =
      7). Vibration (30 Hz, 2-mm displacement) was applied to four sites, four times
      for 10 s, with 5 s of rest in between. Right and left forward-split (RFS and LFS)
      flexibility was measured by the distance between the ground and the anterior
      suprailiac spine. A force plate (sampling rate, 1000 Hz) recorded countermovement
      and static jump characteristics. Explosive strength variables included flight
      time, jump height, peak force, instantaneous forces, and rates of force
      development. Data were analyzed using Bonferroni adjusted paired t-tests.
      RESULTS: VS had statistically increased flexibility (P) and large effect sizes
      (d) in both the RFS (P = 1.28 x 10(-7), d = 0.67) and LFS (P = 2.35 x 10(-7), d =
      0.72). VS had statistically different results of favored (FL) (P = 4.67 x 10(-8),
      d= 0.78) and nonfavored (NFL) (P = 7.97 x 10(-10), d = 0.65) legs. VF resulted in
      statistical increases in flexibility and medium d on RFS (P = 6.98 x 10(-3), d =
      0.25) and statistically increased flexibility on VF NFL flexibility (P = 0.002, d
      = 0.31). SF had no statistical difference between measures and small d. For
      explosive strength, there were no statistical differences in variables in the VS,
      SES, and VES for the pre- versus posttreatment tests. CONCLUSIONS: Simultaneous
      vibration and stretching may greatly increase flexibility while not altering
      explosive strength.

PMID- 18091013
TI  - Assessment of speed and position during human locomotion using nondifferential
      GPS.
AB  - PURPOSE: To validate a nondifferential global positioning system (GPS) to measure
      speed, displacement, and position during human locomotion. METHODS: Three healthy
      participants walked and ran over straight and curved courses for 59 and 34
      trials, respectively. A nondifferential GPS receiver provided speed data by
      Doppler shift and change in GPS position over time, which were compared with
      actual speeds determined by chronometry. Displacement data from the GPS were
      compared with a surveyed 100-m section, and static positions were collected for 1
      h and compared with the known geodetic point. RESULTS: GPS speed values on the
      straight course were closely correlated with actual speeds (Doppler shift: r =
      0.9994, P < 0.001, Delta GPS position/time: r = 0.9984, P < 0.001). Actual speed
      errors were lowest using the Doppler shift method (90.8% of values within +/- 0.1
      m x s(-1)). Speed was slightly underestimated on a curved path, though still
      highly correlated with actual speed (Doppler shift: r = 0.9985, P < 0.001, Delta
      GPS distance/time: r = 0.9973, P < 0.001). Distance measured by GPS was 100.46 +/
      0.49 m, and 86.5% of static points were within 1.5 m of the actual geodetic
      point (mean error: 1.08 +/- 0.34 m, range 0.69-2.10 m). CONCLUSIONS:
      Nondifferential GPS demonstrated a highly accurate estimation of speed across a
      wide range of human locomotion velocities using only the raw signal data with a
      minimal decrease in accuracy around bends. This high level of resolution was
      matched by accurate displacement and position data. Coupled with reduced size,
      cost, and ease of use, this method offers a valid alternative to differential GPS
      in the study of overground locomotion.

PMID- 18091014
TI  - Effect of eccentric training on the plantar flexor muscle-tendon tissue
      properties.
AB  - PURPOSE: It has been shown that eccentric training can be effective in the
      rehabilitation of patients with Achilles tendonopathy. The mechanism behind these
      results is not clear. However, there is evidence that tendons are able to respond
      to repeated forces by altering their structure and composition, and, thus, their
      mechanical properties change. In this regard, the objective of the present study
      was to investigate whether eccentric training affects the mechanical properties
      of the plantar flexor's muscle-tendon tissue properties. METHODS: Seventy-four
      healthy subjects were randomized into two groups: an eccentric training group and
      a control group. The eccentric training group performed a 6-wk eccentric training
      program for the calf muscles. Before and after this period, all subjects were
      evaluated for dorsiflexion range of motion using universal goniometry, passive
      resistive torque of the plantar flexors, and stiffness of the Achilles tendon.
      Passive resistive torque was measured during ankle dorsiflexion on an isokinetic
      dynamometer. Stiffness of the Achilles tendon was assessed using a dynamometer,
      in combination with ultrasonography. RESULTS: The results of the study reveal
      that the dorsiflexion range of motion was significantly increased only in the
      eccentric training group. The eccentric heel drop program also resulted in a
      significant decrease of the passive resistive torque of the plantar flexors (from
      16.423 +/- 0.827 to 12.651 +/- 0.617 N.m). The stiffness of the Achilles tendon
      did not change significantly as a result of training. CONCLUSION: These findings
      provide evidence that an eccentric training program results in changes to some of
      the mechanical properties of the plantar flexor muscles. These changes were
      thought to be associated with modifications to structure rather than to stretch
      tolerance.

PMID- 18091015
TI  - Blood lactate during recovery from intense exercise: impact of inspiratory
      loading.
AB  - PURPOSE: It has long been suggested that inspiratory muscle activity may impact
      blood lactate levels ([Lac(-)]B) during the recovery from dynamic exercise. In
      this study, we tested the hypothesis that inspiratory muscle activation during
      recovery from intense exercise would contribute to La clearance, thus leading to
      reduced [Lac(-)]B. METHODS: Twelve healthy men underwent two maximal, incremental
      exercise tests on different days. During a 20-min inactive recovery period, they
      breathed freely or against a fixed inspiratory resistance of 15 cm H2O. During
      recovery, pulmonary gas exchange was continuously monitored, and serial samples
      of arterialized venous blood were obtained for [Lac(-)]B, pH, PCO2, and HCO3(-).
      RESULTS: Subjects presented similar ventilatory and gas-exchange responses at
      peak exercise during both experimental conditions. [Lac(-)]B during recovery was
      reduced with inspiratory resistance (7.7 +/- 1 vs 10.4 +/- 1, 7.8 +/- 2 vs 10.3
      +/- 2, and 7.3 +/- 1 vs 9.7 +/- 2 mM at 5, 7, and 9 min of recovery,
      respectively; P < 0.05), but no differences were found for blood acid-base
      status. Inspiratory resistance was associated with increased metabolic demand (V
      O2 and V CO2) but improved ventilatory efficiency, with lower V E/[V CO2] and
      increased alveolar ventilation. CONCLUSION: These data are consistent with the
      notion that inspiratory muscles may be net consumers of lactate during recovery
      from intense exercise.

PMID- 18091016
TI  - Growth hormone isoform responses to GABA ingestion at rest and after exercise.
AB  - Oral administration of the amino acid/inhibitory neurotransmitter gamma
      aminobutyric acid (GABA) reportedly elevates resting serum growth hormone (GH)
      concentrations. PURPOSE: To test the hypothesis that GABA ingestion stimulates
      immunoreactive GH (irGH) and immunofunctional GH (ifGH) release at rest and that
      GABA augments the resistance exercise-induced irGH/ifGH responses. METHODS:
      Eleven resistance-trained men (18-30 yr) participated in this randomized, double
      blind, placebo-controlled, crossover study. During each experimental bout,
      participants ingested either 3 g of GABA or sucrose placebo (P), followed either
      by resting or resistance exercise sessions. Fasting venous blood samples were
      acquired immediately before and at 15, 30, 45, 60, 75, and 90 min after GABA or P
      ingestion and were assayed for irGH and ifGH. RESULTS: At rest, GABA ingestion
      elevated both irGH and ifGH compared with placebo. Specifically, peak
      concentrations of both hormones were elevated by about 400%, and the area under
      the curve (AUC) was elevated by about 375% (P < 0.05). Resistance exercise (EX-P)
      elevated time-point (15-60 min) irGH and ifGH concentrations compared with rest
      (P < 0.05). The combination of GABA and resistance exercise (EX-GABA) also
      elevated the peak, AUC, and the 15- to 60-min time-point irGH and ifGH responses
      compared with resting conditions (P < 0.05). Additionally, 200% greater irGH (P <
      0.01) and 175% greater ifGH (P < 0.05) concentrations were observed in the EX
      GABA than in the EX-P condition, 30 min after ingestion. GABA ingestion did not
      alter the irGH to ifGH ratio, and, under all conditions, ifGH represented
      approximately 50% of irGH. CONCLUSIONS: Our data indicate that ingested GABA
      elevates resting and postexercise irGH and ifGH concentrations. The extent to
      which irGH/ifGH secretion contributes to skeletal muscle hypertrophy is unknown,
      although augmenting the postexercise irGH/ifGH response may improve resistance
      training-induced muscular adaptations.

PMID- 18091017
TI  - Carbohydrate availability and muscle energy metabolism during intermittent
      running.
AB  - PURPOSE: To examine the influence of ingesting a carbohydrate-electrolyte (CHO-E)
      solution on muscle glycogen use and intermittent running capacity after
      consumption of a carbohydrate (CHO)-rich diet. METHODS: Six male volunteers (mean
      +/- SD: age 22.7 +/- 3.4 yr; body mass (BM) 75.0 +/- 4.3 kg; V O2 max 60.2 +/-
      1.6 mL x kg(-1) x min(-1)) performed two trials separated by 14 d in a
      randomized, crossover design. Subjects consumed either a 6.4% CHO-E solution or a
      placebo (PLA) in a double-blind fashion immediately before each trial (8 mL x kg(
      1) BM) and at 15-min intervals (3 mL x kg(-1) BM) during intermittent high
      intensity running to fatigue performed after CHO loading for 2 d. Muscle biopsy
      samples were obtained before exercise, after 90 min of exercise, and at fatigue.
      RESULTS: Subjects ran longer in the CHO-E trial (158.0 +/- 28.4 min) compared
      with the PLA trial (131.0 +/- 19.7 min; P < 0.05). There were no differences in
      muscle glycogen use for the first 90 min of exercise (approximately 2 mmol of
      glucosyl units per kilogram of dry matter (DM) per minute). However, there was a
      trend for a greater use in the PLA trial after 90 min (4.2 +/- 2.8 mmol x kg(-1)
      DM x min(-1)) compared with the CHO-E trial (2.5 +/- 0.7 mmol x kg(-1) DM x min(
      1); P = 0.10). Plasma glucose concentrations were higher at fatigue in the CHO-E
      than in the PLA trial (P < 0.001). CONCLUSIONS: These results suggest that CHO-E
      ingestion improves endurance capacity during intermittent high-intensity running
      in subjects with high preexercise muscle glycogen concentrations. The greater
      endurance capacity cannot be explained solely by differences in muscle glycogen,
      and it may actually be a consequence of the higher plasma glucose concentration
      towards the end of exercise that provided a sustained source of CHO for muscle
      metabolism and for the central nervous system.

PMID- 18091018
TI  - Active and passive tension interact to promote Akt signaling with muscle
      contraction.
AB  - PURPOSE: The extent to which factors associated with muscle contraction activate
      Akt remains unclear. This study examined the influences of mechanical (active and
      passive tension), neural (activation frequency), and metabolic (glycogen
      depletion) factors on Akt activation during in situ contractions. METHODS: Muscle
      length was modified to produce comparable active contractile forces in three
      protocols, despite a twofold difference in stimulation frequency (15 vs 30 Hz); a
      fourth protocol used 30-Hz stimulation at optimal length to produce greater
      active forces. Two protocols were performed at optimal length, using 15- or 30-Hz
      stimulation (15 Hz opt and 30 H zopt, respectively). Two other protocols used 30
      Hz stimulation at shortened or lengthened positions (30 Hz sub and 30 Hz supra,
      respectively). RESULTS: The principal finding was that the 30-Hz opt protocol
      induced significantly greater Akt phosphorylation (approximately threefold
      relative to control) than did the other protocols, suggesting that activation of
      this signaling pathway is most sensitive to active tension. This result could not
      be attributed to differences in glycogen depletion, stimulation frequency, or
      fatigue. Despite producing the lowest force-time integral, the 30-Hz supra
      protocol, which had the greatest passive tension, exhibited a greater degree of
      Akt phosphorylation than did the 15-Hz opt and 30-Hz sub protocols. Although
      these differences were not significant, they suggest a possible secondary role
      for passive tension, which may interact with active tension in activating the Akt
      signaling pathway. CONCLUSION: Akt activation seems more sensitive to active
      contractile tension than to passive tension. Activation frequency seems to play
      no role in the phosphorylation of Akt.

PMID- 18091019
TI  - The effects of regular strength training on telomere length in human skeletal
      muscle.
AB  - PURPOSE: The length of DNA telomeres is an important parameter of the
      proliferative potential of tissues. A recent study has reported abnormally short
      telomeres in skeletal muscle of athletes with exercise-associated fatigue. This
      important report raises the question of whether long-term practice of sports
      might have deleterious effects on muscle telomeres. Therefore, we aimed to
      compare telomere length of a group of power lifters (PL; N = 7) who trained for 8
      +/- 3 yr against that of a group of healthy, active subjects (C; N = 7) with no
      history of strength training. METHODS: Muscle biopsies were taken from the vastus
      lateralis, and the mean and minimum telomeric restriction fragments (TRF)
      (telomere length) were determined, using the Southern blot protocol previously
      used for the analysis of skeletal muscle. RESULTS: There was no abnormal
      shortening of telomeres in PL. On the contrary, the mean (P = 0.07) and the
      minimum (P = 0.09) TRF lengths in PL tended to be higher than in C. In PL, the
      minimum TRF length was inversely correlated to the individual records in squat (r
      = -0.86; P = 0.01) and deadlift (r = -0.88; P = 0.01). CONCLUSION: These results
      show for the first time that long-term training is not associated with an
      abnormal shortening of skeletal muscle telomere length. Although the minimum
      telomere length in PL remains within normal physiological ranges, a heavier load
      put on the muscles means a shorter minimum TRF length in skeletal muscle.

PMID- 18091020
TI  - Gait speed and step-count monitor accuracy in community-dwelling older adults.
AB  - Accurate assessment of physical activity (PA) is necessary to identify the
      sedentary older individual who is in need of activity intervention. Activity
      monitors are quite popular, although it has been suggested that they are less
      accurate at slow gait speeds. PURPOSE: To examine the accuracy of the three
      activity monitors in older individuals who walk at various gait speeds. METHODS:
      Participants were 34 community-dwelling older men and women (mean age 79.2) who
      were asked to simultaneously wear three activity monitors: the Yamax DigiWalker
      (DW) pedometer (hip), the Actigraph (AG) accelerometer (hip), and the StepWatch
      activity monitor (SAM) (ankle). Monitor accuracy was evaluated against observed
      steps taken during a 100-step walking test. Percent error of the monitors was
      calculated as [(monitor steps - observed steps)/observed steps] x 100.
      Participants were categorized into three groups (< 0.80, 0.80-1.0, > 1.0 m x s(
      1)) according to gait speed, which was determined by a timed 4-m walk. RESULTS:
      Overall, the DW and AG failed to detect 16% and 7% of observed steps,
      respectively, and the SAM overestimated by 5.5%. When stratified by gait speed,
      all three monitors faired well at the gait speeds > 1.0 m x s(-1). For gait
      speeds between 0.80 and 1.0 m x s(-1), the SAM overestimated steps by 6.6%, and
      the AG and DW underestimated steps by 5.7% and 12.7%, respectively. However, at
      gait speeds < 0.80 m x s(-1), the AG and DW performed poorly, underestimating
      steps by 19.1% and 31.2%, whereas the SAM performed better, having overestimated
      steps by 6.5%. CONCLUSIONS: All three objective activity monitors performed well
      at moderate and higher walking speeds, but at decreased gait speeds, the SAM
      seemed to be the most accurate.

PMID- 18091021
TI  - Effect of physical activity on menopausal symptoms among urban women.
AB  - PURPOSE: To determine whether physical activity, measured by expended
      kilocalories per week (kcal.wk), decreases the risk of menopausal symptoms among
      African American and Caucasian women. METHODS: Level of physical activity and
      menopausal symptoms, including hot flashes, depression, anxiety, stress, and
      vasomotor, physiological, and somatic symptom summaries were measured in 401
      women during an 8-yr period. Tertiles of physical activity at each assessment
      were defined as kilocalories per week: top third (>or= 1450 kcal x wk(-1)),
      middle third (< 1450 to 644 kcal x wk(-1)), and bottom third (< 644 kcal x wk(
      1)). Regression models were used to estimate the independent effect of physical
      activity at each time period on menopausal symptoms after adjusting for
      covariates and hormone levels. Results were also stratified by race, smoking
      status, and menopausal status. RESULTS: Overall, only perceived stress was
      related to level of physical activity, with women in both the middle and top
      tertiles of physical activity reporting lower mean levels of stress compared with
      women in the lowest tertile of activity. In the analysis by menopausal stage,
      active postmenopausal women continued to report lower mean levels of anxiety,
      stress, and depressive symptoms compared with inactive postmenopausal women. We
      did not find an association between level of physical activity and reports of hot
      flashes, even after adjusting for the variability in the hormonal changes.
      CONCLUSIONS: Among a cohort of community-dwelling women, high levels of physical
      activity were related to lower levels of stress during an 8-yr follow-up period.
      In addition, levels of anxiety, stress, and depression were lowest among
      physically active postmenopausal women compared with inactive women in the same
      menopausal grouping.

PMID- 18091022
TI  - The relation of fatness to insulin is independent of fitness in 9- but not 15-yr
      olds.
AB  - PURPOSE: To explore the relationship between varying aerobic fitness (fitness),
      fatness, and fasting insulin levels in healthy children. METHODS: A population
      based sample of 9-yr-old (9YO, 47 boys, 56 girls) and 15-yr-old (15YO, 53 boys,
      51 girls) Icelandic children. Body fatness was evaluated via body mass index,
      waist circumference adjusted for height (waist adj), and sum of four skinfolds.
      Fitness was assessed with a graded maximal cycle ergometer test. Fasting insulin
      was measured using an ECLIA. RESULTS: Fasting insulin correlated to all fatness
      measures (9YO, r = 0.43-0.46, P < 0.001; 15YO, r = 0.30-0.37, P < 0.003) and
      fitness (9YO, r = -0.29, P = 0.003; 15YO, r = -0.32, P = 0.001). Adjustment for
      fitness did not affect the relations between fatness and fasting insulin in 9YO
      (r = 0.33-0.37, P < 0.001); however, only waist adj remained significantly
      related to fasting insulin (r = 0.24, P = 0.016) in 15YO. Children in the upper
      half of fitness and fatness split on the median did not differ in fasting insulin
      from children in the upper half of fitness but lower half of fatness. Fatness was
      related to fasting insulin in 9YO (r = 0.51-0.54, P = 0.001) and 15YO (r = 0.31
      0.35, P = 0.011-0.028) in the lower half of fitness, but no association was
      observed in the upper half of fitness in either group. CONCLUSION: Fatness has a
      greater association with fasting insulin than fitness, especially among 9YO;
      however, fitness attenuates the adverse relation of fatness to fasting insulin in
      15YO but does not change it in 9YO. In both age groups, being fitter and fatter
      does not result in greater fasting insulin than being fitter and leaner, and
      fatness is primarily associated with fasting insulin in lower-fit children.

PMID- 18091023
TI  - SNPs in PPARG associate with type 2 diabetes and interact with physical activity.
AB  - PURPOSE: To study the associations of seven single-nucleotide polymorphisms
      (SNPs) in the peroxisome proliferator-activated receptor gamma (PPARG) gene with
      the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D),
      and the interactions of the SNPs with physical activity (PA). METHODS: Overweight
      individuals with IGT who participated in the Finnish Diabetes Prevention Study
      (DPS) (N = 479) were followed, on average, 4.2 yr. PA was assessed yearly with a
      12-month validated questionnaire. RESULTS: In Cox regression analyses, the rare
      alleles of rs17036314 and rs1801282 (Pro12Ala) predicted conversion to T2D (P =
      0.038 and 0.037, respectively), but only rs17036314 predicted T2D after
      adjustment for baseline fasting glucose (P = 0.030). The change in the total
      amount of PA, stratified by median, modified the association of rs17036314 and
      rs1801282 with the risk of T2D during the intervention (P = 0.002 and 0.031,
      respectively, for interaction between PA change and genotype); an increase in PA
      seemed to remove the effect of the risk alleles. The distinct rs1152003
      polymorphism interacted with the study group on the conversion to T2D (P = 0.027)
      and tended to increase the risk of T2D in the intervention group (P = 0.050). No
      interaction between rs1152003 and the change in PA was found. CONCLUSIONS: The
      rs17036314, rs1801282 (Pro12Ala), and rs1152003 were associated with the risk of
      T2D in the DPS. Increased PA seemed to decrease the effect of the risk alleles of
      rs17036314 and rs1801282 on the conversion to T2D. The effect of rs1152003 was
      modified by other lifestyle changes or the lifestyle intervention as a whole.

PMID- 18091024
TI  - Nutritional supplementation and anabolic steroid use in adolescents.
AB  - PURPOSE: To examine nutritional supplementation and anabolic steroid (AS) use in
      adolescent males and females in a multistate, cross-regional study. A secondary
      purpose of the study was to investigate the knowledge, beliefs, and sources of
      education on nutritional supplementation and AS in these students. METHODS: A
      confidential self-report survey was administered to 3248 students representing
      grades 8-12 in 12 states in the continental United States by their teachers
      during homeroom or physical education class. RESULTS: Use of at least one
      supplement was reported by 71.2% of the adolescents surveyed. The most popular
      supplements used were multivitamins and high-energy drinks. The use of
      supplements to increase body mass and strength, and to reduce body fat or mass,
      increased across grade and was more prevalent in males than females. The number
      of students that self-reported AS use was 1.6% (2.4% males and 0.8% females). The
      number of supplements used was related to AS use among adolescents, and this
      effect was greater among males. Adolescents also seemed willing to take more
      risks with supplements to achieve their fitness or athletic goals, even if these
      risks reduced health or caused premature death. CONCLUSION: This study
      demonstrates that reliance on nutritional supplements increases as adolescents
      mature. The apparent willingness of adolescents to use a supplement that may harm
      their health or shorten their life highlights the need for greater involvement of
      teachers, coaches, and physicians to provide continued education on the risks and
      benefits associated with nutritional supplementation and AS use.

PMID- 18091025
TI  - Attenuation of muscle metaboreflex in chronic obstructive pulmonary disease.
AB  - PURPOSE: Abnormal skeletal muscle function is well documented in chronic
      obstructive pulmonary disease, but there is no information about the activity of
      muscle metabosensitive afferents. In this study, we tested the hypothesis that
      patients with chronic obstructive pulmonary disease would have abnormal reflex
      responses to stimulation of metabosensitive afferents in skeletal muscle when
      compared with healthy, matched subjects. METHODS: In 16 patients with moderate to
      severe chronic obstructive pulmonary disease and 13 healthy, age-matched control
      subjects, we evaluated heart rate, mean blood pressure, calf blood flow, and calf
      vascular resistance responses to static handgrip exercise at 30% of maximal
      voluntary contraction, followed by recovery with or without circulatory
      occlusion. Muscle metaboreflex control of calf vascular resistance was estimated
      by subtracting the area under the curve with circulatory occlusion from the area
      under the curve without circulatory occlusion. RESULTS: Mean blood pressure and
      heart rate responses were not significantly different in patients and controls
      during exercise and recovery. In the control group, calf vascular resistance
      increased significantly during exercise and remained elevated above baseline
      during circulatory occlusion, whereas in patients changes from rest were not
      significantly different in both trials. Estimated muscle metaboreflex control of
      calf vascular resistance was significantly reduced in the patients (controls: 31
      +/- 22 units, patients: 8 +/- 31 units, P < 0.05). CONCLUSION: Patients with
      chronic obstructive pulmonary disease have a reduced calf vascular resistance
      response to handgrip exercise and to selective activation of muscle metaboreflex
      when compared with healthy subjects.

PMID- 18091027
TI  - Seroepidemiology of human papillomavirus type 11 in the United States: results
      from the third National Health And Nutrition Examination Survey, 1991--1994.
AB  - OBJECTIVES: The national seroprevalence of the nononcogenic human papillomavirus
      (HPV) type 11, one of the types targeted by the quadrivalent HPV vaccine, has not
      been evaluated in the United States. The objectives of this study were to
      estimate the national seroprevalence and evaluate predictors of HPV-11
      seropositivity. STUDY DESIGN: We tested serum samples for HPV-11 antibodies and
      analyzed questionnaire data from the second phase of the National Health and
      Nutrition Examination Survey III, 1991--1994. Seroprevalence estimates were
      weighted to represent the US population. RESULTS: : Overall seroprevalence of HPV
      11 infection was 4.7%. Seroprevalence was significantly higher among females
      (5.7%) than among males (3.6%). Independent predictors of HPV-11 seropositivity
      included sex, race/ethnicity, lifetime number of sex partners, education, and HPV
      16 seropositivity. CONCLUSION: This study represents the most comprehensive
      picture of HPV-11 infection in the United States to date, and provides baseline
      data on the prevalence of HPV-11 before availability of the quadrivalent HPV
      vaccine.

PMID- 18091026
TI  - Impaired systemic oxygen extraction at maximum exercise in pulmonary
      hypertension.
AB  - PURPOSE: To determine the relative contributions of the Fick principle variables
      to impaired exercise tolerance in pulmonary arterial hypertension compared with
      pulmonary venous hypertension. METHODS: One hundred forty-seven consecutive,
      complete, clinically indicated cardiopulmonary exercise tests done with radial
      and pulmonary arterial catheters and radionuclide ventriculographic scanning were
      screened for an exercise limit attributable to 1) pulmonary arterial hypertension
      (N = 34), 2) left ventricular systolic (N = 23), or 3) diastolic dysfunction (N =
      36), defined by mean pulmonary artery pressure, pulmonary capillary wedge
      pressure, and left ventricular ejection fraction. Systolic and diastolic
      dysfunction are together referred to as pulmonary venous hypertension. Patients
      with other limits were excluded, including those with a pulmonary mechanical
      limit. For the resulting 93 exercise tests, the Fick principle variables'
      contributions to a depressed maximum oxygen consumption were compared by ANOVA
      and ANCOVA. RESULTS: Maximum oxygen consumption (54.5 +/- 15.5 vs 73.2 +/- 20.1
      vs 66.0 +/- 15.7% predicted) and oxygen delivery (1457 +/- 456 vs 2161 +/- 824 vs
      2007 +/- 665 mL x min(-1)) were reduced in systolic dysfunction versus both
      diastolic dysfunction and pulmonary arterial hypertension, respectively (P < 0.05
      by ANOVA). Maximum systemic oxygen extraction ratio was highest in systolic
      dysfunction, intermediate in diastolic dysfunction, and lowest in pulmonary
      arterial hypertension (0.744 +/- 0.091 vs 0.680 +/- 0.091 vs 0.619 +/- 0.113,
      respectively, P < 0.05 among all groups). Systemic oxygen extraction at peak
      exercise was inversely related to maximum cardiac output in pulmonary arterial
      hypertension, but it was blunted versus systolic dysfunction throughout the range
      of peak cardiac outputs (P < 0.05 by ANCOVA). CONCLUSIONS: Maximum systemic
      oxygen extraction is impaired in pulmonary arterial versus pulmonary venous
      hypertension and contributes to the exercise limit.

PMID- 18091028
TI  - Application of optical coherence tomography for monitoring changes in
      cervicovaginal epithelial morphology in macaques: potential for assessment of
      microbicide safety.
AB  - OBJECTIVES: Safety is a primary concern in the development of topical
      microbicides. Optical coherence tomography (OCT), a high-resolution, in-depth
      cross-sectional imaging modality, was utilized in conjunction with colposcopy to
      assess induced cervicovaginal epithelial changes that may predict product safety.
      STUDY DESIGN: OCT and colposcopic images of macaque vaginal and cervical tissues
      were obtained in excised tissue and in vivo under various conditions, including
      mechanical injury and nonoxynol-9 treatment. RESULTS: A scoring system was
      developed to categorize and quantify the OCT images based on morphologic features
      that indicate the presence or absence of an intact epithelial layer and
      inflammation. Using 3 categories (normal, mild to moderately abnormal, and
      severely abnormal), differences between healthy and injured tissue were apparent
      on OCT images. Normal images (category 1) had a bilayered structure
      representative of the epithelium and submucosa. Mild to moderately abnormal
      images (category 2) had areas of normal and abnormal epithelium. Severely
      abnormal images (category 3) had complete loss of the epithelium and/or
      inflammation, with loss of the bilayered structure on OCT. CONCLUSIONS: OCT is a
      noninvasive imaging modality complementary to colposcopy. It distinguished
      between normal and abnormal (or injured) tissue and thus holds promise for safety
      evaluations of candidate microbicides and other vaginal products.

PMID- 18091029
TI  - Understanding the characteristics of effective mass media campaigns for back pain
      and methodological challenges in evaluating their effects.
AB  - STUDY DESIGN: Workshop at the Low Back Pain Forum VIII: Primary Care Research on
      Low Back Pain held in Amsterdam in June 2006. OBJECTIVES: The aim of the workshop
      was to 1) describe and compare characteristics and outcomes of back pain media
      campaigns that have taken place internationally; 2) examine general theories of
      health behavior change from the mass media literature to determine whether it is
      possible to develop a theoretical framework to explain the observed outcomes; 3)
      describe the outcome of discussion and expert consensus around lessons learned
      from these campaigns that may inform the planning and evaluation of future
      campaigns; and 4) identify priorities for future research. SUMMARY OF BACKGROUND
      DATA: Mass media campaigns designed to alter societal views about back pain have
      now been performed in several countries. Although these types of campaigns are an
      established strategy for delivering preventive health messages, there is limited
      empirical understanding of the characteristics of effective (or ineffective)
      health campaigns. METHODS: We reviewed the content and outcome of back pain mass
      media campaigns conducted in Australia, Norway, and Canada using the Cochrane
      Effective Practice and Organization of Care Review Group data collection
      checklist. We also reviewed models of health behavior change that could be used
      to guide the design, planning, and evaluation of future campaigns. The draft
      article was reviewed by a group of international back pain experts before forming
      the basis for discussion at the workshop. Expert comments and those of workshop
      participants were synthesized and incorporated into the final manuscript.
      RESULTS: The outcome of discussion and expert consensus around lessons learned
      from these campaigns are described. CONCLUSION: Our article may help to inform
      the planning and evaluation of future campaigns and identify priorities for
      future research.

PMID- 18091030
TI  - Pulling together: interagency coordination and HIV/STD prevention.
AB  - Using multiple network comparisons, we determined whether sexually transmitted
      disease (STD) rates or black-white STD rate differences are related to how HIV
      prevention agencies interact through exchanges of information, clients, or funds.
      In 10 North Carolinian counties, we conducted a cross-sectional analysis, using
      each county's network as the unit of interest. Using data from face-to-face
      interviews, measures of the density (overall connectedness) and degree
      centralization (amount of centralized information hubs) were calculated with
      UCINET. Statistical significance of the associations between county
      characteristics and STD rates was assessed with exact Wilcoxon rank sum test.
      Syphilis rates were lower (P = .01) in counties with a high network density, on
      the basis of exchanges of information or clients. The effect on black-white rate
      differences was in the same direction but weaker. Where network degree
      centralization was high, syphilis rates were higher and the black-white rate
      differences were larger. Gonorrhea rates demonstrated similar but attenuated
      patterns of association with network characteristics. STD prevention is more
      effective when all agencies interact with each other (density) but less effective
      when interactions are predominantly with a few central agencies (degree
      centralization). The measures of network exchanges employed in this study may be
      appropriate for future assessment of service provision of funded prevention
      programs.

PMID- 18091032
TI  - Credentialing in public health: the time has come.

PMID- 18091031
TI  - African Americans' organ donor intentions: who has used which registration mode
      to express her or his intentions?
AB  - AIM: To describe the various means that African American adults had used to
      express their intention to become an organ donor, as well as to determine whether
      there were characteristics that distinguished those individuals who had expressed
      their intention from those individuals who had not. PARTICIPANTS: Participants
      were 1 567 African American adults who resided in four urban areas in New Jersey.
      METHODS: From July 2005 to April 2006, university survey center interviewers
      conducted 7-minute, random-digit-dial telephone interviews. RESULTS:
      Approximately 3.2 percent reported that they had donated an organ; 3.4 percent
      reported being an organ recipient; 11.4 percent reported that a family member had
      donated an organ or tissue; and 12 percent reported that a family member was a
      recipient. Forty-six percent reported that they had indicated their willingness
      to be an organ donor when they applied for a driver's license; 37 percent had
      done so by discussing their wishes with family members. Fewer had signed an organ
      donor card (21%) or had signed up with an organ donor registry (16%). A multiple
      logistic regression model revealed a negative association between the
      respondent's age and whether the respondent had expressed an intention to be a
      donor, and a positive association between having known a family member who had
      received or donated an organ and the respondent's intention. Neither gender nor
      marital status was associated with the intention to donate. CONCLUSIONS: As the
      driver's license was the means favored by African Americans for declaring their
      intentions to be organ donors, motor vehicle registries appear to hold the
      greatest promise for documenting and communicating this intention.

PMID- 18091033
TI  - Retaining program diversity in undergraduate public health education.

PMID- 18091034
TI  - Who will keep the public healthy? The case for undergraduate public health
      education: a review of three programs.
AB  - While most universities have focused on graduate education to create public
      health leaders, undergraduate public health education is another way to ensure a
      prepared workforce at all levels. This article provides examples of three Council
      on Education for Public Health accredited graduate programs outside schools of
      public health (University of Southern California, Temple University, and New York
      University) that also offer undergraduate public health education, one that is in
      its first year of offering a public health minor, and the other two offering
      majors and minors. Although these programs come from different philosophies, all
      have an underlying mission to influence how public health is understood.
      Considering the current need for public health workers, we anticipate that most
      higher education institutions will soon offer undergraduate public health
      courses. These programs must be mindful, however, of newly emerging accreditation
      requirements, which might have implications for both established and newly
      developing undergraduate public health programs, as well as articulation issues
      between undergraduate- and graduate-level master of public health programs. An
      examination of existing programs, as well as a discussion of accreditation
      requirements and articulation issues, will help institutions create curricula
      that meet their students' educational needs as well as the need for a strong
      public health workforce.

PMID- 18091035
TI  - The public health role in the primary prevention of diabetes: recommendations
      from the chronic disease directors' project.
AB  - AIM: The article reports on the recommendations from the Diabetes Primary
      Prevention Project that was initiated and funded by the Division of Diabetes
      Translation, Centers for Disease Control and Prevention, and developed by the
      National Association of Chronic Disease Directors. METHOD: Essential components
      of statewide programs are delineated for effective interventions for diabetes
      primary prevention. The recommendations were derived from a structured process
      that is detailed on the basis of a cross-comparison of state-level diabetes
      prevention initiatives in six states where such programs were most developed.
      RESULTS: The recommendations focus on state-level partnerships, statewide program
      planning, required resources, policies, benchmarks for progress, and data
      collection. CONCLUSION: Illustrations are provided regarding how the project
      influenced the six participating states in further developing their programs for
      the primary prevention of diabetes.

PMID- 18091036
TI  - The challenges of addressing primary prevention of diabetes: a response to
      recommendations from the chronic disease directors' project.
AB  - The growing burden of diabetes in the United States is leading public health
      entities to reconsider the focus of their efforts to prevent and control the
      disease. In particular, they are striving to include primary prevention in their
      agendas. Many program reports and projects, specifically the chronic disease
      directors project, recommend effective ways to prevent diabetes. Science supports
      the need for primary prevention of diabetes, but the most effective ways to
      implement the chronic disease directors project's recommendations remain unclear.
      The purpose of this commentary is to review the programmatic challenges faced by
      a federal diabetes public health entity, the Division of Diabetes Translation.
      These include limited funding, little coordination of primary prevention efforts
      among disease-oriented programs, limited research on effective interventions, and
      the large population at risk for developing diabetes. We discuss these challenges
      with reference to the primary prevention of diabetes, but they have broader
      implications for the different public health entities (federal, state, and
      nongovernmental organizations) with a vested interest in diabetes because they
      attempt to implement similar primary prevention recommendations for other
      diseases.

PMID- 18091037
TI  - Diabetes prevention in a faith-based setting: results of translational research.
AB  - AIM: The purpose of this study was to translate the National Institutes of Health
      (NIH)-Diabetes Prevention Program (DPP) into a church-based setting. METHODS: The
      lifestyle arm of the NIH-DPP was implemented in an African American Baptist
      church. Church members 18 years or older completed a risk screen during Sunday
      service followed by fasting glucose (FG) testing at the church during the week.
      Persons with prediabetes participated in a 16-session DPP conducted over 4
      months. Participation rates, height, weight, blood pressure (BP) and FG were
      followed for 12 months post-intervention. Fifty participants completed the risk
      screen, 26 were at risk for diabetes, 16 of 26 received FG testing, and 8 had
      prediabetes (FG = 100- 125 mg/dL). RESULTS: The mean participation rate was 10.4
      (65%) sessions. Following the intervention, weight, systolic and diastolic BP,
      and FG decreased by 7.5 lb (3.6%), 16 mm Hg (11.7%), 12 mm Hg (14.0%), and 5
      mg/dL (4.8%), respectively (P < .05). In comparison with baseline, significant
      reductions were evident at 6 and 12 months postintervention for all endpoints.
      CONCLUSIONS: This study demonstrated successful translation of the 16-session NIH
      DPP into a church-based setting. Future studies should test this intervention in
      churches of different sizes and denominations.

PMID- 18091038
TI  - DC Water and Sewer Authority and lead in drinking water: a case study in
      environmental health risk management.
AB  - In 2001, following a change in disinfection agent in anticipation of the
      Environment Protection Agency Disinfection Byproduct Rule, lead levels began
      rising in drinking water in Washington, District of Columbia, and in 2002, the DC
      Water and Sewer Authority was found to have exceeded the Environment Protection
      Agency lead action level, requiring compliance with a series of measures under
      the Lead and Copper Rule. In 2004, the issue became a public concern, drawing
      considerable media attention. The problem was eventually resolved through the
      application of orthophosphate but while it played out, the utility was forced to
      respond to a novel public health issue with few risk management options. This
      case study examines the lessons learned.

PMID- 18091039
TI  - Examining the front lines of local environmental public health practice: a
      Maryland case study.
AB  - OBJECTIVE: Local environmental public health (EPH) is the foundation of a
      nation's environmental protection infrastructure. With increasing pressure to
      demonstrate the ability of EPH activities to effectively protect health, the
      Johns Hopkins Center for Excellence in EPH Practice, as part of the Centers for
      Disease Control and Prevention's (CDC's) EPH capacity-building effort, developed
      the Profile of Maryland Environmental Public Health Practice. This profile offers
      an examination of front-line local EPH strengths, needs, challenges, and provides
      recommendations to strengthen the EPH infrastructure. METHODS: A multistep
      process was conducted, including site visits to all of Maryland's 24 local EPH
      agencies and a questionnaire addressing administrative structure, communication,
      funding, workforce, crisis management, technology, and legal authority, completed
      by local EPH directors. RESULTS: The Maryland Profile revealed a dedicated and
      responsive workforce limited by a neglected, fragmented, and underfunded EPH
      infrastructure. Recommendations regarding leadership, workforce, training,
      technology, communication, and legal authority are offered. CONCLUSIONS: This
      research has implications for the national EPH infrastructure. Recommendations
      offered are consistent with the CDC's findings in A National Strategy to
      Revitalize Environmental Public Health Services. These findings and
      recommendations offer opportunities to facilitate the advancement of an EPH
      system to better protect the nation's health.

PMID- 18091040
TI  - University environmental health program recruitment and stability: a systems
      analysis.

PMID- 18091041
TI  - Improving disease reporting by clinicians: the effect of an internet-based
      intervention.
AB  - OBJECTIVES: Disease surveillance by clinicians is critical to public health
      activities, yet studies have demonstrated significant underreporting of
      reportable diseases by clinicians. We sought to determine whether an intervention
      utilizing electronic media increases public health reporting by clinicians.
      METHODS: A nonrandomized, controlled design with 24-week baseline and
      intervention outcome periods was used. Five intervention hospitals in the county
      of Philadelphia received a three-component intervention that included e-mail
      memoranda, a Web site, and a handheld computer program. Intervention components
      provided education and information to assist with reporting. Control hospitals
      comprised all remaining hospitals in the county. RESULTS: E-mails were sent to
      more than 16500 clinicians and administrative personnel at five hospitals on each
      of three occasions. The Web site received 866 visits, and the handheld computer
      program was downloaded 130 times. Intervention hospitals had a mean increase of
      5.6 reports, whereas control hospitals had a mean decrease of 3.0 reports (P =
      .02). CONCLUSIONS: The electronic information-based intervention led to a
      significant increase in clinician reporting of reportable diseases. Considering
      the ease and low cost of implementing such programs, they are an attractive
      method for increasing clinician reporting of public health conditions.

PMID- 18091042
TI  - Service-based research: linking public health research and practice to improve
      the quality of public health programs.

PMID- 18091044
TI  - Creating public health management teams that work.

PMID- 18091043
TI  - Using evaluation to guide successful development of an online training course for
      healthcare professionals.
AB  - AIM: The Centers for Disease Control and Prevention developed an online training
      course to address a lack of knowledge among healthcare professionals regarding
      the identification of patients at risk for hemochromatosis and recognition of its
      related early symptoms. A multilevel evaluation design was used to (a) guide
      course development, (b) test course efficacy, and (c) assess training impact.
      METHODS: Highly focused, brief evaluation activities with the intended audience
      (N = 642) provided a stream of qualitative and quantitative data that guided
      course design, development, and implementation. RESULTS: The training course had
      intended positive impacts on healthcare professionals' knowledge and perceived
      competence in recognizing, diagnosing, and treating hemochromatosis. Both
      physicians and nurses directly attributed changes in their clinical practice to
      course participation including increases in appropriate diagnostic biochemical
      testing for iron overload in new and existing patients. CONCLUSIONS: The
      hemochromatosis course is a successful learning tool that has the desired impact
      on learning and knowledge reinforcement. The evaluation conducted provided a
      stream of evidence that was useful in course development as well as assessment of
      training outcomes. The detailed evaluation plan description may serve as a
      template for assessing other online continuing education training courses that
      address public health issues.

PMID- 18091045
TI  - NACCHO's Health Equity Campaign: dialogue to action.

PMID- 18091046
TI  - Novel low-cost assay for the monitoring of CD4 counts in HIV-infected
      individuals.
AB  - Several CD4 lymphocyte enumeration methods have been developed to be used as
      alternatives to conventional flow cytometry. However, no consensus has been
      reached on which technique should be widely adopted. We introduce here a novel
      nonflow cytometric method, called CD4 Select, for enumeration of CD4 lymphocytes.
      Instead of using a flow cytometer, the method requires only an automatic
      hematoanalyzer (complete blood count [CBC] machine). The correlations of the
      percentage of CD4 lymphocytes and absolute CD4 counts with the CD4 Select method
      and standard flow cytometry were 0.932 and 0.922, respectively. The CD4 Select
      method yielded percentage of CD4 lymphocytes greater than flow cytometry by a
      mean of 0.06%, and the limits of agreement at 95% confidence interval (CI) were
      9.46% to -9.56% using Bland-Altman analysis. The CD4 select method is cheap,
      valid, and simple enough to be conducted locally at small facilities. The method
      yields not only absolute CD4 lymphocytes, but also percentage of CD4 lymphocytes.
      The use of a hematoanalyzer also gives this method relatively high sample
      throughput and makes it less labor-intensive than other nonflow cytometric
      methods.

PMID- 18091047
TI  - Transforming growth factor-beta/transforming growth factor-betaRII signaling may
      regulate CD4+CD25+ T-regulatory cell homeostasis and suppressor function in
      feline AIDS lentivirus infection.
AB  - We have reported that CD4+CD25+ T-regulatory (Treg) cells are fully activated for
      suppressor function in feline immunodeficiency virus (FIV)-infected cats. Studies
      have suggested that surface transforming growth factor-beta (TGFbeta; membrane
      TGFbeta [mTGFbeta]) is a feature of activated CD4+CD25+ Treg cells and may play a
      role in Treg homeostasis and suppressor function. Herein, we explore the role of
      TGFbeta in feline Treg homeostasis and suppressor function and what effect FIV
      infection of cats might have on these processes. Stimulation of CD4+CD25- T
      helper (Th) cells with Concanavalin A (ConA) plus TGFbeta converts them to Treg
      like cells capable of suppressor function. Reverse-transcription polymerase chain
      reaction and flow cytometry revealed that these ConA/TGFbeta-converted Treg cells
      upregulate Foxp3 and mTGFbeta. ConA stimulation of CD4+CD25- T cells upregulates
      TGFbeta receptor II (RII), and pretreatment of these cells with anti-TGFbeta-RII
      antibodies blocks the TGFbeta-induced conversion to Treg cells. Pretreatment of
      ConA/TGFbeta-converted Treg cells with anti-TGFbeta antibodies also abrogates
      their suppressor function, suggesting that Treg homeostasis and suppressor
      function may be mediated by mTGFbeta. Finally, we show that treatment of
      CD4+CD25+ mTGFbeta-positive Treg cells from FIV-infected cats with anti-TGFbeta
      antibodies or treatment of ConA-stimulated CD4+CD25- Th target cells with anti
      TGFbeta-RII antibodies diminishes suppressor function. These data suggest that
      the recruitment of Treg cells from the Th pool and suppressor function of Treg
      cells are dependent on the TGFbeta/TGFbeta-RII signaling pathway and that this
      pathway is constitutively upregulated in asymptomatic chronically FIV-infected
      cats.

PMID- 18091049
TI  - Angiosarcomas of the breast: a review of 70 cases.
AB  - OBJECTIVE: Angiosarcoma arising in the irradiated breast after breast-conserving
      therapy is being reported with increasing frequency. As more women undergo breast
      conserving therapy, the incidence can be expected to increase. The objective of
      this study was to review breast angiosarcomas diagnosed from 1981 to 2000 from
      our state cancer registry. METHODS: A comprehensive review of a population-based
      registry, Florida Cancer Data System, identified 70 cases of breast angiosarcomas
      from 1981 to 2000. Descriptive statistical and chi analyses were performed.
      RESULTS: Of the 70 cases at presentation, 39 were primary breast angiosarcomas
      (PBAs) and 31 were secondary breast angiosarcomas (SBAs). The mean ages were 59
      and 72.9 for the PBA and SBA groups, respectively. In the SBA group the mean age
      of breast cancer diagnosis was 67.6. The mean time to diagnosis of the
      angiosarcoma was 5.2 years after breast cancer irradiation. At presentation 82%
      (n = 32) and 48% (n = 15), in the PBA and SBA groups, respectively had local
      disease (P = 0.003). The primary treatment was mastectomy in each group. There
      was no difference in mortality between the 2 groups (PSA; n = 18, SBA; n = 17).
      CONCLUSION: Angiosarcoma of the breast is rare and this study reports a review of
      70 cases from 1980 to 2000. Angiosarcoma after breast-conserving therapy is
      increasingly diagnosed in a small but significant portion of breast carcinoma
      survivors. SBA patients present with more advance disease. Surgical resection is
      the primary therapy. The aggressive nature of this disease demands further
      investigation of adjuvant therapy to prevent recurrence of disease after surgery.

PMID- 18091050
TI  - Mammographic surveillance after MammoSite breast brachytherapy: analysis of
      architectural patterns and additional interventions.
AB  - PURPOSE: To report the post-treatment mammographic findings of patients who
      received MammoSite brachytherapy at the Medical University of South Carolina
      (MUSC). MATERIALS AND METHODS: A total of 126 mammograms from a cohort of 38
      patients who underwent MammoSite breast brachytherapy and post-treatment
      mammographic follow-up exclusively at MUSC are the subject of this analysis.
      Surveillance mammography commenced at 6 months after completion of brachytherapy
      and was repeated every 6 to 12 months thereafter, depending on Breast Imaging
      Reporting and Data System (BI-RADS) classification and further testing
      recommendations. Patients were clinically assessed at least every 3 months and
      all available data were reviewed for documentation of mammographic findings and
      subsequent interventions. The minimum and median follow-up was 6 and 28 months,
      respectively. RESULTS: Of the 126 mammograms analyzed, 22 (17%) were classified
      as BI-RADS category 2, 93 (74%) as category 3, 10 (8%) as category 4, and 1
      (0.8%) as category 5. Further descriptions of the BI-RADS 3 studies were: 61
      (65%) "surgical changes," 30 (32%) seromas, and 2 (2%) dystrophic calcifications.
      Additional interventions followed 10 (11%) of BI-RADS 3 studies, all revealing
      benign findings. All BI-RADS 4 or 5 studies led to needle aspiration (3) or
      breast biopsy (8). Two biopsies were positive for malignancy, and both were
      classified as elsewhere breast failures. CONCLUSION: Mammographic architectural
      patterns observed after partial breast irradiation and potential differences with
      respect to those traditionally seen following whole breast radiotherapy have yet
      to be well characterized. Our experience may be of clinical utility in the
      counseling of patients until data from randomized trials becomes available.

PMID- 18091051
TI  - Improved survival, quality of life, and quality-adjusted survival in breast
      cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation
      therapy for brain metastases.
AB  - OBJECTIVE: To determine whether efaproxiral, an allosteric modifier of
      hemoglobin, improves quality of life and quality of survival in patients with
      primary breast cancer and brain metastases when used as an adjunct to whole-brain
      radiation therapy (WBRT). METHODS: Patients with brain metastases from breast
      cancer were randomly assigned to receive WBRT and either efaproxiral or no
      efaproxiral. The primary endpoint for this analysis was quality of life and
      quality-adjusted survival. Quality of life was assessed prior to initiation of
      WBRT and periodically in follow-up using the Spitzer Quality of Life Index
      (SQLI). RESULTS: A subgroup of 106 eligible breast cancer patients with baseline
      SQLI were randomized into this study and represent the target population
      discussed in this report. Treatment, age, and SQLI were significant predictors of
      survival. The addition of efaproxiral to WBRT reduced the death rate by 46% (P =
      0.0086). Quality of life was improved in the WBRT + efaproxiral arm compared with
      the WBRT alone arm (P = 0.019). Quality-adjusted survival was statistically
      significantly improved by the addition of efaproxiral to WBRT (P = 0.001).
      CONCLUSION: Survival, quality of life, and quality-adjusted survival were all
      improved in breast cancer patients with brain metastases receiving efaproxiral
      and WBRT compared with those receiving WBRT alone.

PMID- 18091052
TI  - Obesity is not predictive of overall survival following permanent prostate
      brachytherapy.
AB  - PURPOSE: To evaluate the impact of obesity on cause-specific (CSS), biochemical
      progression-free (bPFS), and overall survival (OS) following prostate
      brachytherapy. MATERIALS AND METHODS: From April 1995 through March 2003, 1093
      consecutive patients underwent brachytherapy for clinical T1b-T3a (2002 AJCC)
      prostate cancer. The median follow-up was 5.6 years. Evaluated body mass index
      (BMI) subgroups were < 25 (n = 258), 25.0 to 29.9 (n = 547), 30.0 to 34.9 (n =
      214), and > or = 35 (n = 74) kg/m2, respectively. A total of 430 (39.9%) and 589
      (53.9%) of the patients received androgen deprivation therapy or supplemental
      external beam radiation therapy, respectively. Multiple clinical, treatment, and
      dosimetric parameters were evaluated as predictors of CSS, bPFS, and OS. RESULTS:
      The 11-year CSS, bPFS, and OS for the entire cohort were 97.5%, 95.6%, and 77.6%,
      respectively. BMI did not impact CSS or bPFS for any of the BMI cohorts. However,
      OS was statistically lower in patients with a BMI < 25 kg/m2 (P = 0.014). A Cox
      linear regression analysis demonstrated that Gleason score was the best predictor
      of CSS while percent-positive biopsies, risk group, V100 and hypertension
      predicted for bPFS. Patient age and tobacco use were the strongest predictors of
      OS. A total of 128 patients have died with 108 (84.4%) of the deaths the result
      of cardiovascular/pulmonary disease (73) and second malignancies (35). To date,
      12 patients have died of metastatic prostate cancer. CONCLUSION: Obesity did not
      impact CSS, bPFS, or OS in patients treated with permanent prostate
      brachytherapy. Cardiovascular or pulmonary disease and second malignancies
      substantially outweighed prostate cancer as competing causes of death.

PMID- 18091053
TI  - The prognostic significance of Gleason pattern 5 in prostate cancer patients
      treated with Pd-103 brachytherapy.
AB  - OBJECTIVE: To determine the effect of high-grade prostate cancer (Gleason pattern
      5) on the prognosis of patients treated with Pd-103 brachytherapy. METHODS: A
      total of 499 higher-risk patients [Gleason score 7 or higher or prostate-specific
      antigen (PSA) 10-20 ng/mL] treated on a prospective protocol with Pd-103 and
      supplemental external beam radiation were studied. All prostate biopsies were
      reviewed for Gleason grade by 2 pathologists (L.T. and J.V.). Along with
      assignment of a Gleason score based on established criteria, the presence of any
      pattern 5 cancer was separately noted and photographed for future review. Freedom
      from biochemical failure was defined as a serum PSA < or = 0.5 ng/mL at last
      follow-up. RESULTS: The biochemical control rate at 3 years for all 499 patients
      was 86%, with 348 patients followed beyond that time. Patients without pattern 5
      cancer had an 89% rate of biochemical control at 3 years, versus 72% in the 87
      patients with pattern 5 cancer (P = 0.0001). In Cox multivariate regression
      analysis, which included Gleason score, highest Gleason pattern, and pretreatment
      PSA, the Gleason score was the single most important predictor of biochemical
      control (P < 0.0001). CONCLUSION: The presence of pattern 5 disease is a risk
      factor for biochemical failure. But in sharp contrast to prior studies, Pd-103
      brachytherapy-based radiation appears to provide such patients with a high
      likelihood of cancer eradication.

PMID- 18091054
TI  - Clinical presentation and outcomes of lymphocyte-predominant Hodgkin disease at
      the University of Florida.
AB  - OBJECTIVE: To examine the clinical presentation and treatment outcomes of
      lymphocyte-predominant Hodgkin disease (LPHD) at the University of Florida over a
      37-year period. METHODS AND MATERIALS: A retrospective review of the clinical
      presentation and treatment outcomes in 34 patients with LPHD treated at the
      University of Florida from 1968 to 2005 was conducted. The end points of absolute
      survival, cause-specific survival, and relapse-free survival were assessed and
      late treatment sequelae were identified. RESULTS: Ninety-six percent of patients
      presented with stage I/II disease. None had mediastinal disease, 4 (12%) had
      bulky disease (>6 cm in maximum tumor dimension), and only 1 (3%) had B symptoms.
      Eighty percent of patients were treated with radiation therapy (RT) alone and 20%
      with RT and chemotherapy. At 5, 10, and 15 years, absolute survival was 97%, 85%,
      and 76%; cause-specific survival was 100%, 95%, and 95%; and relapse-free
      survival was 93%, 81%, and 74%. No patients died with Hodgkin disease, but 1
      patient's death was attributed to treatment-related late sequelae. There were 6
      treatment failures, including 2 within the RT field; all failures were
      successfully salvaged. The median time to relapse was 5.8 years (range, 2.9-14.6
      years). Three secondary malignancies were observed. CONCLUSION: LPHD patients
      typically present at an early stage without B symptoms, mediastinal, or bulky
      disease. First-line treatment with RT alone yields excellent results in
      appropriately selected patients and remains the standard of care. Relapses often
      occur late and long-term follow-up is needed to successfully diagnose and treat
      late relapses.

PMID- 18091055
TI  - A retrospective study of definitive chemoradiotherapy for elderly patients with
      esophageal cancer.
AB  - OBJECTIVE: The efficacy and safety of definitive chemoradiotherapy (CRT) for
      elderly patients with esophageal cancer have not been fully elucidated yet. We
      conducted a retrospective comparison of the outcomes of CRT between elderly and
      nonelderly patients with Stage II-III (non-T4) esophageal cancer. METHODS: There
      were 33 elderly (aged over 71) patients and 145 nonelderly (aged under 70)
      patients who fulfilled the selection criteria. The treatment consisted of the
      continuous infusion of fluorouracil (5-FU) and the intravenous infusion of
      cisplatin (CDDP) combined with 60 Gy of radiation. RESULTS: Although the CR rate
      was almost identical between the 2 groups (63.6% vs. 63.4%, respectively), the
      recurrence rate after CR was higher in the elderly patients group than in the
      nonelderly patients group (47.6% vs. 33.7%, P = 0.32). The elderly patient group
      showed a significantly inferior survival in comparison to the nonelderly patient
      group with a median survival time (14.7 months vs. 35.1 months, P = 0.01).
      Discontinuations at the end of CRT were more frequent in the elderly patient
      group than in the nonelderly patients (57.6% vs. 17.3%, P = 0.01). In addition,
      over Grade 3 hematologic adverse events were more frequently observed in elderly
      patients than in nonelderly patients. There were no obvious differences in
      patients who died of causes other than primary disease. CONCLUSION: This
      retrospective analysis revealed a significantly inferior efficacy even in
      selected elderly patients. Although improving the dose intensity of CRT should be
      desirable even in elderly patients, it seems to be difficult because of more
      substantial toxicity in elderly patients.

PMID- 18091056
TI  - Radiotherapy for squamous cell carcinoma of the nasal vestibule.
AB  - OBJECTIVE: To evaluate the efficacy of radiotherapy (RT) alone or combined with
      surgery for the treatment of the nasal vestibule squamous cell carcinomas.
      METHODS: Seventy-one patients with squamous cell carcinoma of the nasal vestibule
      were treated with definitive RT at the University of Florida, and 8 patients with
      advanced T4 cancers were treated with combined surgery and RT. Patients were
      followed from 4 months to 27.7 years (mean 9.0 years, median 7.9 years). Follow
      up on living patients ranged from 6 months to 27.7 years (mean 10.0 years, median
      8.1 years). RESULTS: The 5-year outcomes were: local control, 87%; local-regional
      control, 77%; freedom from distant metastases, 94%; cause-specific survival, 90%;
      and survival, 76%. The 5-year local control rates for patients treated with
      definitive RT were: T1-T2, 95%; T4, 71%; and overall, 86% (P = 0.0046). Local
      control was achieved in 8 of 8 patients treated with surgery and RT. CONCLUSION:
      RT results in a high cure rate for T1-T2 and favorable T4 tumors. Surgery and RT
      result in an improved likelihood of cure for patients with extensive T4.

PMID- 18091057
TI  - Megavoltage computed tomography: an emerging tool for image-guided radiotherapy.
AB  - BACKGROUND: Helical tomotherapy is a unique approach to image-guided IMRT that
      combines features of a linear accelerator and a CT scanner. This design allows
      generation of megavoltage CT (MVCT) images, which among other uses, are used to
      verify daily setup. In this study, we assessed the image-quality, absorbed
      radiation doses, and clinical practicality of MVCT from our helical tomotherapy
      prototype unit. MATERIALS AND METHODS: Phantom studies were first performed to
      assess the capabilities of MVCT. Next, MVCT images from human patients
      prospectively enrolled on institutional review board-approved imaging and
      treatment protocols were analyzed. MVCT was obtained using a 4-MV beam from the
      University of Wisconsin helical tomotherapy prototype device. These scans were
      compared with conventional kilovoltage (kVCT) images from a diagnostic CT
      scanner. RESULTS: MVCT images in phantoms demonstrate an ability to detect
      contrast differences as small as 3%. Small objects, 1.2 to 1.6 mm, were seen with
      good resolution. In human subjects, MVCT imaging of tumor targets and normal
      anatomy revealed sufficient detail for patient repositioning. MVCT imaging of
      metallic objects showed minimal artifact in comparison with kVCT. Patient scans
      were obtained in about 1 to 5 minutes and resulted in absorbed radiation doses of
      1.5 to 3 cGy. CONCLUSIONS: MVCT is an elegant pretreatment position and setup
      verification tool. MVCT images of human subjects obtained from the helical
      tomotherapy unit showed good resolution and contrast. The high-quality three
      dimensional information permits its use in day-to-day setup verification. The
      unique properties of MVCT also provide the potential for primary imaging of
      anatomic regions near metal prostheses as well as nonmedical applications.
      Additional investigations are underway to improve image quality, further reduce
      patient dose, and aid adaptive radiotherapy and dose reconstruction.

PMID- 18091058
TI  - A comprehensive review of the treatment of Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is an uncommon but malignant cutaneous neuroendocrine
      carcinoma with a high incidence of local recurrence, regional lymph node
      metastases, and subsequent distant metastases. The etiology of MCC remains
      unknown. It usually occurs in sun-exposed areas in elderly people, many of whom
      have a history of other synchronous or metachronous sun-associated skin lesions.
      The outcome for most patients with MCC is generally poor. Surgery is the mainstay
      of treatment. The role of adjuvant therapy has been debated. However, data from
      recent development support a multimodality approach, including surgical excision
      of primary tumor with adequate margins and sentinel lymph node dissection
      followed by postoperative radiotherapy in most cases, as current choice of
      practice with better locoregional control and disease-free survival. Patients
      with regional nodal involvement or advanced disease should undergo nodal
      dissection followed by adjuvant radiotherapy and, perhaps, systemic platinum
      based chemotherapy in most cases.

PMID- 18091059
TI  - Stereotactic body radiation therapy: a comprehensive review.
AB  - Stereotactic body radiation therapy (SBRT) is a novel technique that takes
      advantage of the technologic advancements in image guidance and radiation dose
      delivery to direct ablative doses to tumors with acceptable toxicity that was not
      previously achievable with conventional techniques. SBRT requires a high degree
      of confidence in tumor location provided by high quality diagnostic and near real
      time imaging studies for accurate treatment delivery and precise assessment of
      physiologic tumor motion. In addition, stringent dosimetric parameters must be
      applied, paying close attention to the spatial arrangement of functional subunits
      in the adjacent normal tissues, to optimize clinical outcomes. Phase I/II trials
      for tumors of the lung, liver, spine, pancreas, kidney, and prostate provide
      evidence that the potent doses delivered with SBRT may provide results that rival
      surgery while avoiding the typical morbidities associated with that invasive
      approach. Further clinical study in the form of multi-institutional Phase II
      trials is currently underway, and ultimately collaborative efforts on a national
      level to support Phase III trials will be necessary, to firmly establish SBRT as
      a comparable noninvasive alternative to surgery.

PMID- 18091060
TI  - Ameloblastoma.
AB  - The purpose of this article is to review the pertinent literature and discuss the
      optimal treatment and outcomes for patients with ameloblastoma. Ameloblastoma is
      an uncommon benign, locally aggressive odontogenic neoplasm that usually occurs
      in the vicinity of the mandibular molars or ramus. Uncontrolled, ameloblastoma
      may cause significant morbidity and occasionally death. The median age is
      approximately 35 years and males and females are equally affected. The majority
      of ameloblastomas are multicystic, which are more difficult to eradicate than the
      unicystic and peripheral varieties. Although surgery is the mainstay of
      treatment, the extent of resection is controversial. Radical resections,
      including marginal and segmental mandibulectomy, result in local control rates
      exceeding 90%. In contrast, conservative procedures such as enucleation and/or
      curettage result in local control rates of approximately 80% and 50% for
      unicystic and multicystic ameloblastomas, respectively. Limited experience with
      radiotherapy indicates that it may reduce the risk of progression and result in
      long-term local control in the occasional patient with incompletely resectable
      disease. The optimal treatment for ameloblastoma is wide en bloc resection.
      Radiotherapy may improve the likelihood of local control in the occasional
      patient with incompletely resectable tumor.

PMID- 18091061
TI  - Capecitabine and radiotherapy as neoadjuvant treatment for rectal cancer.
AB  - 5-Fluorouracil (5-FU)-based neoadjuvant chemoradiotherapy is used in rectal
      cancer to prolong survival, downsize tumors prior to surgery, and allow for
      sphincter-sparing surgery. Capecitabine is an oral fluoropyrimidine that
      generates 5-FU preferentially within the tumor. It has been shown to be as
      effective as 5-FU and well tolerated in the metastatic and adjuvant settings in
      colorectal cancer. Capecitabine is more convenient for patients than 5-FU, and it
      avoids the risks of infection and thromboembolism associated with intravenous
      administration. It was also shown to reduce the use of medical resources,
      healthcare professionals' time, and cost of therapy. Emerging data from Phase II
      trials of neoadjuvant regimens in which capecitabine has been substituted for 5
      FU are encouraging.

PMID- 18091062
TI  - Burkitt's lymphoma: conversion from lymphoma negative to lymphoma positive status
      over 2 months in a patient with acquired immunodeficiency syndrome (AIDS).

PMID- 18091063
TI  - Myeloid sarcoma presenting in muscle-tissue of the lower limb: unusual origin of
      a compartment-syndrome.

PMID- 18091064
TI  - Haemangiopericytoma of the bladder.

PMID- 18091065
TI  - Basal cell carcinoma with hepatic metastases.

PMID- 18091066
TI  - Herpes simplex encephalitis in a patient with recurrent pituitary adenoma
      receiving radiation therapy.

PMID- 18091067
TI  - Dosimetric concerns regarding the 4-field box technique.

PMID- 18091068
TI  - Performance in specific language tasks correlates with regional volume changes in
      progressive aphasia.
AB  - BACKGROUND: Patterns of language impairment have long been used clinically to
      localize brain damage in stroke patients. The same approach might be useful in
      the differential diagnosis of progressive aphasia owing to neurodegenerative
      disease. OBJECTIVE: To investigate whether scores on 4 widely used language tasks
      correlate with regional gray matter loss in 51 patients with progressive language
      impairment owing to neurodegenerative disease. METHOD: Scores in the Boston
      Naming Test and in the "repetition" "sequential commands" and the "language
      fluency," subtests of the Western Aphasia Battery were correlated with voxel-wise
      gray matter volumes using voxel-based morphometry. RESULTS: Significant positive
      correlations were found between each language task and regional brain volumes:
      (1) naming and the bilateral temporal lobes; (2) sentence repetition and the left
      posterior portion of the superior temporal gyrus; (3) sentence comprehension and
      the left dorsal middle and inferior frontal gyri; and (4) fluency of language
      production and the left ventral middle and inferior frontal gyri. DISCUSSION:
      Performance on specific language tasks corresponds to regional anatomic damage in
      aphasia owing to neurodegenerative disorders. These language tests might be
      useful in the differential diagnosis of primary progressive aphasia variants that
      have been previously associated with damage to corresponding anatomic regions.

PMID- 18091069
TI  - Are cognitive changes progressive in prediagnostic HD?
AB  - OBJECTIVE: To characterize neurocognitive signs of disease progression in
      prediagnosis and early Huntington disease (HD) and compare the sensitivity of 2
      disease staging classification schemes for detecting these signs. METHODS: Three
      hundred and six individuals at-risk for or recently diagnosed with HD completed
      the Unified Huntington's Disease Rating Scale, genetic testing, and a
      neurocognitive battery. Two schemes were used to estimate latency to onset of
      disease. One was based on genetic information (CAG repeat length) and the other
      was based on the extent of motor signs. Effect sizes were compared to assess the
      relative sensitivity of the 2 schemes for detecting signs of disease progression.
      RESULTS: CAG-expanded participants far from estimated diagnosis performed
      similarly to controls, whereas those near to estimated diagnosis were impaired
      relative to controls. Overall, the method employing genetic information yielded
      larger effect sizes than the motor scheme, particularly for strategic and
      executive function measures; the motor scheme resulted in a larger effect size
      for a measure of motor/psychomotor function. CONCLUSIONS: Neurocognitive function
      is not uniformly affected in prediagnosis and early HD; individuals near to their
      estimated age of diagnosis have cognitive signs similar to HD, whereas
      individuals far from estimated diagnosis appear cognitively normal.
      Classification schemes that incorporate both genetic and phenotypic information
      may be more sensitive for tracking neurocognitive signs of disease progression.

PMID- 18091070
TI  - Executive functions deficit in mild cognitive impairment.
AB  - OBJECTIVE: To investigate whether patients diagnosed with amnestic mild cognitive
      impairment (MCI) have also impairment in attention/executive functions, and
      therefore to clarify whether all subcomponents of executive control are equally
      affected in MCI. BACKGROUND: MCI refers to the transitional state between normal
      aging and dementia. Amnestic MCI is characterized by impaired episodic memory,
      although subtle impairment of executive functions has been noted on
      neuropsychologic tests. METHODS: We investigated 20 MCI patients and 20 normal
      controls using episodic memory, attention/executive functions, language, and
      praxis tests. RESULTS: MCI patients had significantly lower scores on all
      measures of the Free and Cued Selective Reminding Test (P<0.05 to 0.01) than
      controls. Furthermore, MCI had a greater number of perseverations (P<0.01) on
      Modified Card Sorting Test and the lowest performance on the Stroop Test
      (P<0.02). CONCLUSIONS: Our findings showed impairment in episodic memory
      performance in MCI as compared with that of controls. In addition, MCI patients
      had problems with response inhibition, switching, and cognitive flexibility,
      which encompass various aspects of executive functions. This suggests that MCI
      may be identified by using a more detailed procedure for the assessment of
      cognitive decline than the evaluation of memory alone.

PMID- 18091071
TI  - Lack of dopaminergic modulation of cognitive flexibility.
AB  - OBJECTIVE: To evaluate performance on a cognitive flexibility task after
      administration of a dopaminergic agonist. BACKGROUND: L-3,4
      dihydroxyphenylalanine, which is converted into dopamine and norepinephrine,
      results in a restriction of the semantic network in priming experiments. Recent
      evidence suggests that flexibility of access to semantic networks in problem
      solving is mediated by the noradrenergic system. We wished to determine if
      dopaminergic agonists also affect this type of cognitive flexibility. METHODS:
      Eighty-four subjects were tested twice on an anagram task, once 1 hour after
      bromocriptine (dopamine agonist) and once 1 hour after placebo administration.
      RESULTS: No difference was detected between placebo and bromocriptine on anagram
      performance. CONCLUSIONS: Therefore, modulation of this type of cognitive
      flexibility does not seem to be mediated by the dopaminergic system. This
      suggests that the noradrenergic modulation of cognitive flexibility previously
      reported does not seem to extend to the dopaminergic system among catecholamines.

PMID- 18091072
TI  - Disruption of reciprocal coordination by a medial frontal stroke sparing the
      corpus callosum.
AB  - Aleksandr Luria described several tests of higher motor function, including the
      "reciprocal coordination" test of bimanual coordination. Although these tests are
      commonly used to assess frontal lobe function, their specific neuroanatomic
      underpinnings are not completely understood. We describe a man with a medial
      frontal stroke sparing the corpus callosum with a defect in Luria's reciprocal
      coordination test but otherwise intact motor abilities, including other tests of
      higher motor function.

PMID- 18091073
TI  - A vanishing lesion in the temporal lobe associated with schizophrenialike
      psychosis and catatonia.
AB  - OBJECTIVE: To present the case of a patient with hallucinations and psychotic
      symptoms that co-occurs with a temporary lesion in the left posterior temporal
      lobe. BACKGROUND: Psychosis and auditory hallucinations are characteristic
      features of schizophrenia, but may also complicate many somatic diseases. Current
      functional imaging studies suggest a role of the temporal lobes. METHOD: We
      describe a patient who initially presented with schizophrenialike psychotic
      symptoms at an age of 23. She did not respond to antipsychotic medication and
      developed severe medication-resistant catatonia. RESULTS: Magnetic resonance
      imaging studies revealed an opaque left temporal lesion that could not be
      diagnosed otherwise. Electroconvulsive therapy led to remission of her catatonic
      and psychotic symptoms. After clinical remission, the temporal lesion had
      vanished. CONCLUSIONS: The longitudinal association between the lesion and the
      occurrence and disappearance of psychosis supports current theories on the role
      of the left temporal lobe in psychosis.

PMID- 18091074
TI  - A case of oral spelling behavior: another environmental dependency syndrome.
AB  - OBJECTIVE: To present the case of a woman with a probable vascular dementia and a
      unique oral spelling behavior (OSB). Our aim was to better characterize the
      mechanisms underlying OSB in this patient with advanced cognitive and
      noncognitive deficits. BACKGROUND: Different kind of language deficits have been
      described in dementias and other related diseases. Other nonaphasic acquired
      communication disorders include a heterogeneous group of verbal impairment that
      are mainly due to attentional and executive impairments. METHODS: We describe the
      neurolinguistic and neuropsychologic analysis of an 88-year-old woman with
      spontaneous OSB. Computed tomography-scan at the time of the clinical analysis is
      also presented. RESULTS: OSB occurred preferentially in spontaneous discourse,
      manifested in other language tasks, concerned all lexical categories, and was not
      accompanied by spelling deficit although language was not intact and disclosed
      foreign accent syndrome. Environmental dependency syndrome or utilization
      behavior was prominent and concerned various sensorimotor activities.
      CONCLUSIONS: We postulate that OSB was not secondary to a linguistic or more
      specifically to a spelling deficit but to another variant of environmental
      dependency syndrome and probably associated with a cortico-subcortical lesion
      including the left prefrontal region.

PMID- 18091075
TI  - The Huntington disease of woody guthrie: another man done gone.
AB  - Woody Guthrie was an American songwriter, musician, writer, and political
      activist who died with Huntington disease (HD) in 1967 at age 55. His relatively
      brief creative life was incredibly productive with countless songs and a
      tremendous volume of letters to his name. His personal life was similarly driven
      with Woody having had 3 wives and at least 9 children and an insatiable appetite
      for traveling the United States. In this essay, I explore Guthrie's art in
      relation to the development of the overt behavioral changes and chorea that
      characterized his illness. Woody's most productive time artistically was in the 5
      years immediately preceding the onset of overt symptoms of HD. I hypothesize that
      subclinical HD may have been an important driving force behind Woody Guthrie's
      creativity.

PMID- 18091076
TI  - Understanding the neuropsychologic outcome of pediatric AVM within a
      neurodevelopmental framework.
AB  - OBJECTIVE: This case series describes the long-term neuropsychologic functioning
      of 5 children with repaired arteriovenous malformations (AVMs). Results are
      presented within the context of a neurodevelopmental model to facilitate
      conceptualization and generate appropriate rehabilitation strategies for children
      with AVMs. BACKGROUND: The current case series expands upon previous research
      examining the long-term psychosocial functioning of these children with AVMs in
      which it was found that overall emotional functioning appeared adequate, although
      there were suggestions of defensiveness and areas of worry. In addition, global
      adaptive functioning was below average for most children with parental concerns
      about their child's socialization. METHOD: Five children with repaired AVMs in
      the cerebellum and frontal, temporal, and parietal lobes participated in a
      neuropsychologic evaluation assessing intellectual, language, memory, motor,
      visual-perceptual and visual-motor, and executive functions. RESULTS: These
      children demonstrated both localized and remote findings. More specifically, mild
      to moderate weaknesses in executive functions were suggested regardless of AVM
      location. CONCLUSIONS: The finding that children exhibited executive function
      difficulties regardless of AVM location is in keeping with the understanding of
      multiple cortical and subcortical pathways to and from the frontal lobes. In
      addition, it is possible that the processes of diaschisis and plasticity may play
      a role in the functional outcome of AVMs.

PMID- 18091077
TI  - Obsessive-compulsive disorder and catatonia can be caused by antibasal ganglia
      antibodies.

PMID- 18091080
TI  - Detection and early identification in bioterrorism events.
AB  - Syndromic surveillance, collecting and analyzing symptoms before diagnosis, has
      the potential to identify bioterrorist attacks in a timely, flexible, and
      specific manner. Nurses are important resources in collecting and interpreting
      surveillance data. Clinical skills in early diagnosis may identify a bioterrorist
      attack before surveillance systems and independently trigger investigations.
      Computerized syndromic surveillance systems are difficult to sustain and are not
      in use nationwide. Traditional public health surveillance is not replaced by
      syndromic surveillance. Weaknesses remain in surveillance related to bioterrorism
      preparedness. Bioterrorist events must be recognized in a timely manner, but this
      is dependent on sufficient funding for training, equipment, and personnel.

PMID- 18091081
TI  - Effective mental health response to catastrophic events: lessons learned from
      Hurricane Katrina.
AB  - This article describes how a mental health disaster response plan, which resulted
      from a collaborative effort between the Arkansas Department of Health and the
      Arkansas Chapter of the National Association of Social Workers, was used
      successfully to meet the needs of more than 1,000 displaced survivors of
      Hurricane Katrina. Included is a discussion of how the components of established
      disaster response protocols can be integrated with evolving theory on the
      psychological effect of catastrophic events on micro-, mezzo-, and macro-level
      systems to advance the field of disaster mental health response.

PMID- 18091082
TI  - Identifying and tracking disaster victims: state-of-the-art technology review.
AB  - The failure of our nation to adequately track victims of Hurricane Katrina has
      been identified as a major weakness of national and local disaster preparedness
      plans. This weakness has prompted government and private industries to
      acknowledge that existing paper-based tracking systems are incapable of managing
      information during a large-scale disaster. In response to this need, efforts are
      under way to develop new technologies that allow instant access to identity and
      location information during emergency situations. The purpose of this article is
      to provide a review of state-of-the-art technologies, with implications and
      limitations for use during mass casualty incidents.

PMID- 18091083
TI  - Geographic analysis of ambulance availability in Arkansas.
AB  - In keeping with emergency medical services (EMS) industry standards, response
      time requirements of EMS units in Arkansas are temporally based and reflect
      traditionally accepted concepts of reasonable access to emergency care services.
      However, time-centric response standards may be unrealistic and may place
      ambulance staff and patients at risk, particularly during mass casualty events.
      In view of the availability of current technology to efficiently re-route EMS
      units on the basis of geographic realities, traditional 4-minute and 8-minute
      response time standards should be reevaluated and replaced by or added to
      standards that emphasize spatially based objectives.

PMID- 18091084
TI  - Families, schools, and disaster: the mental health consequences of catastrophic
      events.
AB  - Children have always experienced or witnessed disaster and mass casualty events
      in their schools and communities. However, the psychological impact of such
      events was not recognized until the middle of the 20th century. Children's
      responses to disaster and other traumatic events are based on developmental
      stage, the specific threat, injury and loss, and the child's coping skills as
      well as previous traumatic experiences. Schools and communities can serve as a
      sanctuary for children and their families during such devastating times. Lessons
      learned from the terrorist attacks of September 2001 and the gulf coast
      hurricanes offer strategies and approaches to assist children for families,
      teachers, schools, and communities. Resources for schools and communities include
      national organizations with evidence-based guidelines, program development, and
      guides for policy and communication.

PMID- 18091085
TI  - In for the long haul: sustaining and rebuilding educational operations after
      Hurricane Katrina.
AB  - In 2005, Hurricane Katrina and the subsequent levee breaks left 80% of New
      Orleans under water for weeks. Within 4 short weeks, the Louisiana State
      University Health Sciences Center at New Orleans had relocated its campus
      temporarily to Baton Rouge and resumed operations. Many lessons were learned in
      the first year of recovery and disseminated to the field regarding emergency and
      disaster preparedness and response. As we approach the second anniversary of the
      nation's most devastating natural disaster, we reflect on the long haul of
      rebuilding and offer new insights and lessons for sustaining operations and
      enhancing long-term rebuilding efforts.

PMID- 18091086
TI  - Predictive failure analysis: planning for the worst so that it never happens!
AB  - This article reviews an alternative approach to failure analysis involving a
      deliberate saboteurial approach rather than a checklist approach to disaster and
      emergency preparedness. This process is in the form of an algorithm that is
      easily applied to any planning situation.

PMID- 18091087
TI  - Stress and emotional problems during pregnancy and excessive infant crying.
AB  - OBJECTIVE: There is evidence that stress and emotional problems during pregnancy
      are related to adverse health outcomes of the child at birth and in later life.
      The aim of this study was to determine the association between stress and
      emotional problems during pregnancy and excessive infant crying. METHODS: From an
      initial sample of 8266 pregnant women, a follow-up sample of 4976 women and their
      3- to 6-month-old babies was examined. Depressive symptoms, pregnancy related
      anxiety, parenting stress, and job strain during pregnancy were all univariately
      and multivariately associated with excessive infant crying (adjusted odds ratios
      between 1.69 and 2.23). RESULTS: Women with three or four of these antenatal
      risks were more likely to have an infant who cries excessively than women with no
      antenatal risks (adjusted odds ratio of 4.89). CONCLUSION: In conclusion, stress
      and emotional problems during pregnancy increase the chances of having an
      excessively crying baby. Women with multiple antenatal risk factors are at
      particular risk.

PMID- 18091088
TI  - Relationship between speech-sound disorders and early literacy skills in
      preschool-age children: impact of comorbid language impairment.
AB  - OBJECTIVE: Disorders of articulation or speech-sound disorders (SSD) are common
      in early childhood. Children with these disorders may be at risk for reading
      difficulties because they may have poor auditory, phonologic, and verbal memory
      skills. METHODS: We sought to characterize the reading and writing readiness of
      preschool children with SSD and identify factors associated with preliteracy
      skills. Subjects were 125 children aged 3 to 6 years with moderate to severe SSD;
      53% had comorbid language impairment (LI). Reading readiness was measured with
      the Test of Early Reading Ability-2 (TERA) and writing skills with the Test of
      Early Written Language-2 (TEWL), which assessed print concept knowledge. Linear
      regression was used to examine the association between SSD severity and TERA and
      TEWL scores and analysis of variance to examine the effect of comorbid LI.
      Performance on a battery of speech and language tests was reduced by way of
      factor analysis to composites for articulation, narrative, grammar, and word
      knowledge skills. RESULTS: Early reading and writing scores were significantly
      lower for children with comorbid LI but were not related to SSD severity once
      language status was taken into account. Composites for grammar and word knowledge
      were related to performance on the TERA and TEWL, even after adjusting for
      Performance IQ. Below average language skills in preschool place a child at risk
      for deficits in preliteracy skills, which may have implications for the later
      development of reading disability. CONCLUSION: Preschool children with SSD and LI
      may benefit from instruction in preliteracy skills in addition to language
      therapy.

PMID- 18091089
TI  - Educational and occupational outcomes among survivors of childhood cancer during
      the transition to emerging adulthood.
AB  - PURPOSE: To examine educational and occupational outcomes among survivors of
      childhood cancer and peers during the transition from adolescence to emerging
      adulthood. METHODS: Families were recruited when children with cancer were 8 to
      15 years old and receiving initial treatment for a malignancy that did not
      primarily affect the central nervous system (CNS). At that time, each child with
      cancer was matched to a classmate of similar age, gender, and race for inclusion
      in a comparison group. For the current follow-up (7.29 years postdiagnosis), 56
      survivors, 60 peers, and their parents completed questionnaires soon after the
      youth's 18th birthday. Severity of treatment and late effects were rated by
      healthcare providers. RESULTS: Survivors and peers were similar on a variety of
      outcomes, including family background, scholastic and occupational self-concept,
      and academic competence. However, survivors were more likely to report repeating
      a grade and having more school absences. The proportion of participants who
      graduated from high school, were working, and expressed plans to attend
      postsecondary education or seek employment were similar between groups. Initial
      treatment intensity, time since diagnosis, and severity of late effects were
      associated with several indices of educational and occupational attainment.
      CONCLUSIONS: Despite being more likely to repeat a grade and miss school,
      survivors of nonCNS cancer were similar to peers on most educational and
      occupational outcomes during the transition from adolescence to emerging
      adulthood. Interventions to assist academic or occupational functioning may not
      be necessary for all survivors, but additional research is needed to identify
      subgroups at risk for difficulties.

PMID- 18091090
TI  - The relationship between television advertising, children's viewing and their
      requests to Father Christmas.
AB  - OBJECTIVE: Children's letters to Father Christmas provide an opportunity to use
      naturalistic methods to investigate the influence of television advertising.
      METHODS: This study investigates the number of toy requests in the letters of
      children aged between 6 and 8 (n = 98) in relation to their television viewing
      and the frequency of product advertisements prior to Christmas. Seventy-six hours
      of children's television were sampled, containing over 2,500 advertisements for
      toys. RESULTS: Children's viewing frequency, and a preference for viewing
      commercial channels, were both related to their requests for advertised goods.
      Gender effects were also found, with girls requesting more advertised products
      than boys. CONCLUSION: Exploring the children's explicit understanding of
      advertising showed that children in this age group are not wholly aware of the
      advertisers' intent and that, together with their good recall of advertising,
      this may account for their vulnerability to its persuasive messages.

PMID- 18091091
TI  - Is difficult temperament related to overweight and rapid early weight gain in
      infants? A prospective cohort study.
AB  - OBJECTIVE: Childhood overweight and rapid weight gain during the first months of
      life have been shown to be major risk factors for the development of later
      overweight. Studies in children show that there are temperamental risk factors
      for the development of overweight, but little is known about early infancy.
      METHODS: The present study investigated the relationship of infant difficult
      temperament, assessed at age 6 months, with overweight status at birth and at 6
      months of age and with rapid weight gain during this period. Data collection was
      conducted as part of the Norwegian Mother and Child Cohort Study at the Norwegian
      Institute of Public Health (1999-2006). The analyses are based on data retrieved
      from the Medical Birth Registry of Norway, health charts, and maternal reports
      during pregnancy and when the child was 6 months of age. After application of
      eligibility criteria, 29,182 infants could be included in the study. RESULTS: In
      adjusting for infants' sex, formula feeding, maternal age, body mass index and
      diabetic status, and parental duration of education, infant difficult temperament
      was slightly negatively associated with overweight status at birth but not at age
      6 months. In addition, infant difficult temperament was slightly positively
      associated with rapid weight gain during the first 6 months of life. CONCLUSIONS:
      Despite statistical significance, these associations do not appear to be
      clinically relevant. Future studies should explore whether the impact of
      temperament increases with age.

PMID- 18091092
TI  - Preadolescent health risk behavior as a function of prenatal cocaine exposure and
      gender.
AB  - OBJECTIVE: To examine the effect of prenatal cocaine exposure on health risk
      behaviors during preadolescence. METHODS: The present study examined prenatal
      cocaine exposure, gender, and environmental risk as predictors of self-reported
      substance use, aggression, and a disregard for safety precautions on the Youth
      Risk Behavior Survey in a sample of 10.5 year olds (n = 154, including 60 who
      were prenatally exposed to cocaine). RESULTS: Gender tended to moderate the
      effects of prenatal cocaine exposure because exposure effects were found for boys
      but not girls. Boys who were prenatally exposed to cocaine reported engaging in
      more high-risk behavior. In examining individual outcomes, cocaine exposed boys
      had the highest scores for aggression, substance use, and a disregard for safety
      precautions, although these differences were significant only for the composite
      health risk behavior measure. CONCLUSIONS: The findings extend earlier work
      showing that prenatal cocaine exposure places boys at risk for problems of
      inhibitory control, emotional regulation, and antisocial behavior. Research is
      needed to examine whether the effects of prenatal cocaine on health risk
      behaviors persist into adolescence, when such behaviors tend to increase.

PMID- 18091093
TI  - Commentary on educational and occupational outcomes among survivors of childhood
      cancer during the transition to emerging adulthood.

PMID- 18091094
TI  - Episodic hypersomnia and unusual behaviors in a 14-year old adolescent.
AB  - CASE: John, a 14-year old white male of European Jewish descent without a prior
      history of medical or psychiatric problems, presented following several days of
      increased need for sleep (16-20 hours per day), disorientation, difficulty
      maintaining attention and concentration, bizarre behaviors. He was sexually
      inappropriate toward his mother, sister, and housekeeper, masturbated in public,
      and sang nonsense lyrics. In addition, he had brief periods of agitation,
      paranoia (including fear that he was being followed and that he would be hurt by
      the physicians), and periods of distraction by auditory and visual
      hallucinations. His appetite increased significantly during this time. One week
      prior to the onset of these symptoms, he traveled to the Midwest where he
      experienced several days of nausea, vomiting, and diarrhea.John's physical and
      neurological examinations were normal except for the behaviors noted above. A
      medical evaluation revealed a normal brain computerized tomogram (CT) and
      magnetic resonance imaging (MRI). Urine toxicology screen, a comprehensive
      metabolic blood panel, and a complete blood count were normal. A lumbar puncture
      demonstrated a slightly elevated opening pressure (24 centimeters); the
      cerebrospinal fluid examination was unremarkable for cells, protein and glucose.
      Following the lumbar puncture, for which he had received midazolam, he had a
      brief, 30-45 minute episode of lucidity in which he was able to describe feeling
      like he was "in a fog."John was transferred to a psychiatric hospital where he
      recovered over several days and was discharged home. After three weeks of
      complete recovery, he acutely developed profound fatigue and the previously seen
      bizarre behaviors returned and persisted for 2 weeks. Following a 2-week period
      without symptoms, a similar behavior pattern recurred for the third time. The
      third episode differed from the first two in that he initially developed mental
      status changes and then developed symptoms of hypersomnolence. John has now been
      completely recovered from the third two week episode for one week and is taking
      summer school classes and enjoying socializing with his friends.

PMID- 18091095
TI  - Rethinking disorders of spoken and written language: generating workable
      hypotheses.
AB  - Disorders of spoken and written language (DSWL) tend to overlap at multiple
      levels: manifestationally, procedurally, developmentally, and etiologically. In
      other words, these disorders exhibit a positive manifold of correlations
      expressed among their different procedural components and in prospective,
      concurrent, and retrospective comorbidity. There is no single accepted
      explanation for this positive manifold of correlations. The purpose of this
      article is to explore this multilayer overlap and to consider whether such a
      positive manifold can be explained by one or all of the three hypotheses
      delineated in the article.

PMID- 18091096
TI  - The effect of brief-tone stimulus duration on the brain stem auditory steady
      state response.
AB  - OBJECTIVE: To investigate the effect of brief-tone stimulus duration on the
      amplitude of the brain stem auditory steady-state response (ASSR), both in single
      and multiple-stimulus conditions. DESIGN: In Experiment 1, the primary stimuli
      were Blackman-windowed 500- and 2000-Hz brief tones presented using repetition
      rates of 79 and 83 Hz, respectively. Stimuli had durations ranging from 0.5 to 12
      msec. In the single-stimulus condition, these two stimuli were presented
      dichotically, whereas in the four-stimulus multiple-stimulus condition, instead
      of being presented alone, each stimulus was combined with three interfering
      stimuli, which were also Blackman-windowed brief tones spaced one octave apart,
      and presented at rates of 77 to 96 Hz. In Experiment 2, the effect of brief-tone
      duration and the effect of interfering stimuli were further studied by
      systematically removing interfering stimuli from the multiple stimuli, with the
      goal of determining which specific stimuli in the multiple stimuli were
      responsible for the interference. In both experiments, stimuli were presented at
      75 ppe dB SPL. The subjects were normal-hearing adults, who relaxed or slept
      during the recording sessions. RESULTS: Experiment 1: ASSR amplitudes increased
      as stimulus duration decreased in the single-stimulus condition, for both 500 and
      2000 Hz. However, amplitudes did not significantly increase until stimuli were
      quite brief (2 msec for 2000 Hz; 6 msec for 500 Hz). In the four-stimulus
      multiple-stimulus condition, the pattern of amplitude increase with decreasing
      stimulus duration at 2000 Hz was similar to that in the single-stimulus
      condition, although amplitudes at all durations were reduced. However, for 500-Hz
      stimuli in the four-stimulus multiple-stimulus condition, ASSR amplitudes showed
      no change as stimulus duration decreased. Experiment 2: for 2000-Hz stimuli, the
      4000-Hz interfering stimuli resulted in the largest change in amplitude, the 1000
      Hz interfering stimuli had a small effect, and the 500-Hz interfering stimuli had
      no effect. For 500-Hz stimuli, the 1000-Hz interfering stimuli had the greatest
      effect, the 2000-Hz interfering stimuli the next largest, and the 4000-Hz
      interfering stimuli a small effect. The interference effects for 500-Hz stimuli
      occurred only for brief (< or =6 msec) stimuli, with no effects of the
      interfering stimuli when the 500-Hz stimuli were 8 or 12 msec in duration.
      CONCLUSION: Although brief tones may result in larger-amplitude ASSRs, their
      duration must be quite brief (not more than three to four cycles) to show a
      significant amplitude increase. Moreover, when presented together with other
      stimuli in the multiple-stimulus technique, response interference reduces the
      amplitudes of ASSRs, and for 500 Hz removes the amplitude gain normally seen with
      decreasing duration. Brief-tone stimuli, therefore, may not be optimal for ASSR
      threshold estimation, especially because of the compromise in frequency
      specificity accompanying the use of very brief tones.

PMID- 18091097
TI  - The influence of different speech processor and hearing aid settings on speech
      perception outcomes in electric acoustic stimulation patients.
AB  - OBJECTIVE: Electric acoustic stimulation (EAS) is an increasingly popular means
      of treating individuals with a steeply sloping mid-to-high frequency hearing
      loss, who traditionally do not benefit from hearing instruments. These persons
      often have too much residual hearing to be considered for a cochlear implant.
      Several studies have demonstrated the ability both to preserve the remaining low
      frequency hearing in these individuals, and to provide significant benefit
      through combining a cochlear implant with a hearing aid to amplify the same ear.
      These improvements in performance have been especially noted in noise. Often
      overlooked is that these outcomes may be influenced by the fitting parameters of
      both the cochlear implant and the hearing aid. DESIGN: This study assessed four
      EAS subjects, with a minimum of 1 month's EAS use, on eight different fitting
      parameters. Sentence testing in different noise levels (+15, +10, and +5 dB SPL)
      was conducted. Subjects also evaluated each condition using a visual analogue
      scale. RESULTS: Results demonstrated that a reduced overlap of cochlear implant
      and hearing aid amplification produced best results across listening conditions.
      CONCLUSIONS: The hearing aid should be fit to a patient-specific modified
      audiogram at least up to the point where low-frequency hearing is not measurable.
      The cochlear implant should be fit from a higher frequency point than is standard
      in patients without residual hearing in the implanted ear, to provide reduced
      overlap with the amplification provided by the hearing aid. Therefore, a small
      amount of overlap between the frequency ranges used by the hearing aid and the
      cochlear implant seems beneficial.

PMID- 18091098
TI  - Universal newborn hearing screening: parental reflections on very early
      audiological management.
AB  - OBJECTIVE: This article seeks to understand very early audiological management
      from a parental perspective, after the early identification of their child's
      hearing loss through universal newborn hearing screening (UNHS). DESIGN: Data are
      taken from the national evaluation of the introduction of UNHS in England. Forty
      five parents and caregivers participated in a qualitative, narrative study within
      which they identified key challenges generated by the audiological management of
      very young babies with hearing loss at home. RESULTS: Concern centered on the
      virtual timetable constructed by parents after screening, the practical daily
      management issues and the need to establish infant rather than a child focus in
      audiological practice. In addition, specific challenges relating to moderate
      hearing loss were identified. CONCLUSIONS: Results are of particular relevance to
      pediatric audiologists, teachers of the deaf and those offering early
      intervention services.

PMID- 18091099
TI  - Multicenter U.S. bilateral MED-EL cochlear implantation study: speech perception
      over the first year of use.
AB  - OBJECTIVE: Binaural hearing has been shown to support better speech perception in
      normal-hearing listeners than can be achieved with monaural stimulus
      presentation, particularly under noisy listening conditions. The purpose of this
      study was to evaluate whether bilateral electrical stimulation could confer
      similar benefits for cochlear implant listeners. DESIGN: A total of 26
      postlingually deafened adult patients with short duration of deafness were
      implanted at five centers and followed up for 1 yr. Subjects received MED-EL
      COMBI 40+ devices bilaterally; in all but one case, implantation was performed in
      a single-stage surgery. Speech perception testing included CNC words in quiet and
      CUNY sentences in noise. Target speech was presented at the midline (0 degrees),
      and masking noise, when present, was presented at one of three simulated source
      locations along the azimuth (-90, 0, and +90 degrees). RESULTS: Benefits of
      bilateral electrical stimulation were observed under conditions in which the
      speech and masker were spatially coincident and conditions in which they were
      spatially separated. Both the "head shadow" and "summation" effects were evident
      from the outset. Benefits consistent with "binaural squelch" were not reliably
      observed until 1 yr after implantation. CONCLUSIONS: These results support a
      growing consensus that bilateral implantation provides functional benefits beyond
      those of unilateral implantation. Longitudinal data suggest that some aspects of
      binaural processing continue to develop up to 1 yr after implantation. The
      squelch effect, often reported as absent or rare in previous studies of bilateral
      cochlear implantation, was present for most subjects at the 1 yr measurement
      interval.

PMID- 18091100
TI  - Hearing handicap ratings among different profiles of adult cochlear implant
      users.
AB  - OBJECTIVE: The aim was to compare outcomes in the domain of self-reported hearing
      handicap across groups of patients fit with one versus two cochlear implants (CI,
      CI + CI), or with an implant and a hearing aid (HA) in the nonimplanted ear (CI +
      HA). DESIGN: The design was retrospective, and a preliminary step was to factor
      analyze the two measures used, namely, the Hearing Handicap Inventory for the
      Elderly (HHIE) and the Hearing Handicap Questionnaire (HHQ). Longer versus
      shorter-term experience with a single implant profile was compared, and further
      analysis confined to patients fit for less than 100 mo across the three profiles.
      Pre- versus postimplant self-report and performance (speech test, localization)
      data were also compared. RESULTS: Three factors were identified in the HHIE,
      labeled Emotional Distress (HHIE), Difficulty in Hearing, and Social Restriction
      (HHIE). Highest handicap score for Emotional Distress (HHIE) was observed in the
      CI + HA group. There were significantly lower scores for Difficulty in Hearing in
      the CI + CI group than in the CI (p = 0.02) or CI + HA (p = 0.001) groups. On the
      Social Restriction (HHIE) subscale, the CI + CI group reported significantly
      lower rating than the CI (p = 0.009) or CI + HA (p = 0.006) groups. Two factors
      were identified in the HHQ, labeled Emotional Distress (HHQ) and Social
      Restriction (HHQ). Significantly higher Emotional Distress (HHQ) score was
      observed in the CI + HA group than in the CI + CI group (p = 0.002);
      significantly lower Social Restriction (HHQ) score was found in the CI + CI group
      than in the CI (p = 0.02) or CI + HA (p < 0.001) groups. Pre-post speech test
      performance showed least contrast in the CI + HA group. CONCLUSIONS: Outcomes
      demonstrate an evident reduction from single or bilateral implantation in the
      area of emotional distress and a further advantage from bilateral implantation in
      the areas of hearing difficulty and social restriction.

PMID- 18091101
TI  - Audiovisual perception of speech in noise and masked written text.
AB  - OBJECTIVE: The aim of this study was to examine the support obtained from
      degraded visual information in the comprehension of speech in noise. DESIGN: We
      presented sentences auditorily (speech reception threshold test), visually (text
      reception threshold test), and audiovisually. Presenting speech in noise and
      masked written text enabled the quantification and systematic variation of the
      amount of information presented in both modalities. Eighteen persons with normal
      hearing (aged 19 to 31 yr) participated. For half of them a bar pattern masked
      the text and for the other half random dots masked the text. The text was
      presented simultaneously or delayed relative to the speech. Using an adaptive
      procedure, the amount of information required for a correct reproduction of 50%
      of the sentences was determined for both the unimodal and the audiovisual
      stimuli. Bimodal support was defined as the difference between the observed
      bimodal performance and that predicted by an independent channels model.
      Nonparametric tests were used to evaluate the bimodal support and the effect of
      delaying the text. RESULTS: Masked text substantially supported the comprehension
      of speech in noise; the bimodal support ranged from 15% to 25% correct. A
      negative effect of delaying the text was observed in some conditions for the
      participants who were presented the text masked by the bar pattern. CONCLUSIONS:
      The ability of participants to reproduce bimodally presented sentences exceeds
      the performance as predicted by an independent channels model. This indicates
      that a relatively small amount of visual information can substantially augment
      speech comprehension in noise, which supports the use of visual information to
      improve speech comprehension by participants with hearing impairment, even if the
      visual information is incomplete.

PMID- 18091103
TI  - Clinical utility of laser-Doppler vibrometer measurements in live normal and
      pathologic human ears.
AB  - The laser-Doppler vibrometer (LDV) is a research tool that can be used to quickly
      measure the sound-induced velocity of the tympanic membrane near the umbo (the
      inferior tip of the malleus) in live human subjects and patients. In this
      manuscript we demonstrate the LDV to be a sensitive and selective tool for the
      diagnosis and differentiation of various ossicular disorders in patients with
      intact tympanic membranes and aerated middle ears. Patients with partial or total
      ossicular interruption or malleus fixation are readily separated from normal
      hearing subjects with the LDV. The combination of LDV measurements and air-bone
      gap can distinguish patients with fixed stapes from those with normal ears. LDV
      measurements can also help differentiate air-bone gaps produced by ossicular
      pathologies from those associated with pathologies of inner-ear sound conduction
      such as a superior semicircular canal dehiscence.

PMID- 18091105
TI  - Interaural time and level difference thresholds for acoustically presented
      signals in post-lingually deafened adults fitted with bilateral cochlear implants
      using CIS+ processing.
AB  - OBJECTIVES: The main purpose of the study was to measure thresholds for
      interaural time differences (ITDs) and interaural level differences (ILDs) for
      acoustically presented noise signals in adults with bilateral cochlear implants
      (CIs). A secondary purpose was to assess the correlation between the ILD and ITD
      thresholds and error scores in a horizontal-plane localization task, to test the
      hypothesis that localization by individuals with bilateral implants is mediated
      by the processing of ILD cues. DESIGN: Eleven adults, all postlingually deafened
      and all bilaterally fitted with MED-EL COMBI 40+ CIs, were tested in ITD and ILD
      discrimination tasks in which signals were presented acoustically through
      headphones that fit over their two devices. The stimulus was a 200-msec burst of
      Gaussian noise bandpass filtered from 100 to 4000 Hz. A two-interval forced
      choice adaptive procedure was used in which the subject had to respond on each
      trial whether the lateral positions of the two sound images (with the interaural
      difference favoring the left and right sides in the two intervals) moved from
      left-to-right or right-to-left. RESULTS: In agreement with previously reported
      data, ITD thresholds for the subjects with bilateral implants were poor. The best
      threshold was approximately 400 microsec, and only five of 11 subjects tested
      achieved thresholds <1000 microsec. In contrast, ILD thresholds were relatively
      good; mean threshold was 3.8 dB with the initial compression circuit on the
      implant devices activated and 1.9 dB with the compression deactivated. The ILD
      and ITD thresholds were higher than previously reported thresholds obtained with
      direct electrical stimulation (generally, <1.0 dB and 100 to 200 microsec,
      respectively). When the data from two outlying subjects were omitted, ILD
      thresholds were highly correlated with total error score in a horizontal-plane
      localization task, computed for sources near midline (r = 0.87, p < 0.01).
      CONCLUSIONS: The higher ILD and ITD thresholds obtained in this study with
      acoustically presented signals (when compared with prior data with direct
      electrical stimulation) can be attributed-at least partially-to the signal
      processing carried out by the CI in the former case. The processing strategy
      effectively leaves only envelope information as a basis for ITD discrimination,
      which, for the acoustically presented noise stimuli, is mainly coded in the onset
      information. The operation of the compression circuit reduces the ILDs in the
      signal, leading to elevated ILD thresholds for the acoustically presented signals
      in this condition. The large magnitude of the ITD thresholds indicates that ITDs
      could not have contributed to the performance in the horizontal-plane
      localization task. Overall, the results suggest that for subjects using bilateral
      implants, localization of noise signals is mediated entirely by ILD cues, with
      little or no contribution from ITD information.

PMID- 18091104
TI  - Aging and speech-on-speech masking.
AB  - OBJECTIVES: A common complaint of many older adults is difficulty communicating
      in situations where they must focus on one talker in the presence of other people
      speaking. In listening environments containing multiple talkers, age-related
      changes may be caused by increased sensitivity to energetic masking, increased
      susceptibility to informational masking (e.g., confusion between the target voice
      and masking voices), and/or cognitive deficits. The purpose of the present study
      was to tease out these contributions to the difficulties that older adults
      experience in speech-on-speech masking situations. DESIGN: Groups of younger,
      normal-hearing individuals and older adults with varying degrees of hearing
      sensitivity (n = 12 per group) participated in a study of sentence recognition in
      the presence of four types of maskers: a two-talker masker consisting of voices
      of the same sex as the target voice, a two-talker masker of voices of the
      opposite sex as the target, a signal-envelope-modulated noise derived from the
      two-talker complex, and a speech-shaped steady noise. Subjects also completed a
      voice discrimination task to determine the extent to which they were able to
      incidentally learn to tell apart the target voice from the same-sex masking
      voices and to examine whether this ability influenced speech-on-speech masking.
      RESULTS: Results showed that older adults had significantly poorer performance in
      the presence of all four types of maskers, with the largest absolute difference
      for the same-sex masking condition. When the data were analyzed in terms of
      relative group differences (i.e., adjusting for absolute performance) the
      greatest effect was found for the opposite-sex masker. Degree of hearing loss was
      significantly related to performance in several listening conditions. Some older
      subjects demonstrated a reduced ability to discriminate between the masking and
      target voices; performance on this task was not related to speech recognition
      ability. CONCLUSIONS: The overall pattern of results suggests that although
      amount of informational masking does not seem to differ between older and younger
      listeners, older adults (particularly those with hearing loss) evidence a deficit
      in the ability to selectively attend to a target voice, even when the masking
      voices are from talkers of the opposite sex. Possible explanations for these
      findings include problems understanding speech in the presence of a masker with
      temporal and spectral fluctuations and/or age-related changes in cognitive
      function.

PMID- 18091106
TI  - Protection from noise-induced temporary threshold shift by D-methionine is
      associated with preservation of ATPase activities.
AB  - OBJECTIVE: The present study was designed to test whether noise-induced temporary
      threshold shift (TTS) could be attenuated by D-methionine and its possible
      relation to the biochemical changes of cochlear lateral walls such as ATPase
      activities and oxidative stress in guinea pigs. DESIGN: Thirty-two normal-hearing
      male guinea pigs were randomly divided into saline-treated and D-methionine
      treated (300 mg/kg) experimental groups. One hour after treatment, they were
      exposed to a continuous broadband white noise at 105 +/- 2 dB sound pressure
      level for 10 min, causing TTS. Each group was then divided into four subgroups
      based on the number of survival days after noise exposure (0, 1, 2, and 7 days).
      Each subgroup had four animals and eight ears included. By means of click-evoked
      auditory brain stem responses (ABR), auditory thresholds of guinea pigs were
      measured before noise exposure, immediately after noise exposure, and before
      killing. After animals were killed, cochlear lateral walls were immediately
      harvested and assayed for enzyme-specific activities of Na+, K+-ATPase and Ca2+
      ATPase, lipid peroxidation, and nitric oxide. RESULTS: A 15.31 +/- 3.80 dB
      threshold shift was found immediately after noise exposure in saline-pretreated
      guinea pigs. In contrast, ABR threshold shift was significantly attenuated to
      4.06 +/- 2.35 dB in D-methionine-treated animals. Furthermore, D-methionine
      enhanced the restoration of ABR threshold to baseline level by 1 day. In
      addition, noise significantly decreased Na+, K+-ATPase, and Ca2+-ATPase
      activities and increased lipid peroxidation and nitric oxide levels of the
      cochlear lateral walls. D-methionine significantly protected against all of these
      changes. CONCLUSIONS: Noise not only induced TTS but also inhibited ATPase
      activities as well as increased oxidative stress in guinea-pig cochlear lateral
      walls; all of these changes could be attenuated by d-methionine through its
      antioxidative property. These results suggest the potential usefulness of d
      methionine in protecting from noise-induced ototoxicity.

PMID- 18091107
TI  - Effect of envelope enhancement on speech perception in individuals with auditory
      neuropathy.
AB  - OBJECTIVES: To investigate the ability to identify consonant-vowel (CV) stimuli
      by individuals with auditory neuropathy (AN) when the envelope of the speech
      signal is enhanced by 15 dB for different modulation bandwidths (3 to 10 Hz; 3 to
      20 Hz; 3 to 30 Hz; 3 to 60 Hz). DESIGN: Eight individuals with auditory
      neuropathy whose pure-tone thresholds ranged from 30 to 70 dB HL participated in
      the present study. Speech material consisted of five lists of CV, one unprocessed
      and four with envelope enhancement. The magnitude of envelope enhancement was 15
      dB and the bandwidths used were 3 to 10 Hz, 3 to 20 Hz, 3 to 30 Hz, and 3 to 60
      Hz. RESULTS: Speech identification scores improved when the envelope of the
      speech was enhanced. The improvement was greater for the broader bandwidth (3 to
      30 Hz) conditions when compared with the smaller bandwidth (3 to 10 Hz and 3 to
      20 Hz) conditions. In the unprocessed condition, manner of articulation was
      transmitted better than voicing and place of articulation. In the envelope
      enhanced conditions, cues for manner and place of articulation were transmitted
      better than voicing. CONCLUSIONS: Envelope enhancement using digital techniques
      improves speech perception by individuals with auditory neuropathy, and it may be
      a viable option for the rehabilitation of these individuals. However, the
      magnitude of envelope enhancement of speech required for maximal improvement of
      speech perception is yet to be determined.

PMID- 18091108
TI  - A quick overview on measuring pressure ulcer prevalence and incidence.

PMID- 18091109
TI  - 2007 National Patient Safety Goals: pressure ulcers.

PMID- 18091113
TI  - Clinicians work to enhance diabetic foot program in Guyana.

PMID- 18091114
TI  - Measuring ankle brachial pressure index.

PMID- 18091115
TI  - 2008 Office of Inspector General's work plan: a "heads-up" for wound care
      providers.

PMID- 18091117
TI  - Best practice recommendations for the prevention, diagnosis, and treatment of
      diabetic foot ulcers: update 2006.
AB  - PURPOSE: To provide the specialist in skin and wound care with evidence-based
      guidelines for care of the person with a diabetic foot ulcer. TARGET AUDIENCE:
      This continuing education activity is intended for physicians and nurses with an
      interest in wound care and related disorders. OBJECTIVES: After reading this
      article and taking this test, the reader should be able to: 1. Describe the
      pathophysiology, assessment, and diagnostic techniques related to diabetic foot
      ulcers. 2. Identify current, evidence-based preventative and treatment options
      for the diabetic foot ulcer.

PMID- 18091120
TI  - Write now!

PMID- 18091121
TI  - Sports cream and arthritic rubs: the hidden dangers of unrecognized salicylate
      toxicity.
AB  - I am a clinical nurse specialist in a busy family practice with many elderly
      patients experiencing osteoarthritis. During an evaluation for the management of
      long-term pain, a patient stated that he would not use a sports cream since he
      had heard on the news that someone had died as a result of use. What are the
      risks and toxicity associated with the use of these pain-relieving products?

PMID- 18091122
TI  - Endurance and inspiration for the entrepreneur.

PMID- 18091123
TI  - Cognitive Appraisal of Health Scale: early instrument development in stroke.
AB  - Stroke, the leading cause of disability in the United States, results in
      significant limitations for an estimated 5.5 million American adults. The degree
      of physical limitations does not explain why some individuals with severe
      impairments adapt well, whereas others with little impairment are severely
      disabled. The concept of cognitive appraisal may partly explain this apparent
      contradiction. The purposes of this early instrument development study were to
      (1) identify appraisals made by community-dwelling stroke survivors and (2) seek
      evidence of the face and content validity for the 3 subscales of the Appraisal of
      Health Scale. A cross-sectional design was used to explore the survivors'
      appraisals. Responses to open-ended questions provided evidence of the face
      validity for all subscales. Threat and benefit subscales had acceptable evidence
      of content validity. Further instrument development is warranted and may lead to
      a more accurate measurement of how stroke survivors appraise the multiple demands
      of stroke recovery.

PMID- 18091124
TI  - Temperament and fatigue management in persons with chronic rheumatic disease.
AB  - BACKGROUND: In persons with chronic conditions, fatigue is often a disruptive
      symptom with a devastating impact on overall well-being. Descriptions of
      experiences with fatigue contribute to advancing knowledge and improving health
      outcomes. AIM: To describe the influence temperament has on fatigue
      representation, self-care strategies, and strategy success. METHOD: A secondary
      analysis of an existing database of personal characteristics and symptom
      experiences of adults with chronic rheumatic diseases was conducted. All
      participants who reported fatigue at least once during the first week of
      participation in the study were included. Relationships were examined among
      demographic variables, temperamental dispositions, and symptom representation.
      RESULTS: Significant relationships were demonstrated between perceived symptom
      seriousness, interference and helpfulness of selected strategies, and both
      demographic variables and temperamental dispositions. CONCLUSIONS: When choosing
      interventions for the individual experiencing fatigue, be aware of demographic
      data and use assessment techniques to promote positive health practices.

PMID- 18091127
TI  - Clinical nurse specialists gain title protection in Pennsylvania.
AB  - Clinical nurse specialists (CNSs) in Pennsylvania will long remember the bright,
      sunny day of July 20, 2007. That was the day Governor Edward G. Rendell signed
      House Bill 1254 into law. Clinical nurse specialists in Pennsylvania finally
      gained title protection! What does this mean? How did it all come about? What are
      the implications for practice?

PMID- 18091126
TI  - Sexual health and quality of life among male veterans with intestinal ostomies.
AB  - PURPOSE: This secondary analysis was conducted to expand our understanding of the
      challenges men with ostomies face regarding intimate relationships and sexual
      functioning. We examined quantitative and qualitative data to examine sexual
      functioning, intimate relationships, and health-related quality of life (HR-QOL)
      among military veterans who are living with an intestinal stoma. SETTING: Three
      Veterans Health Administration sites. SAMPLE: Four hundred eighty-one male
      veterans. METHODS: Case-control, mixed-methods design; cases were those who had
      ostomies for at least 2 months, and controls had a similar major intestinal
      surgical procedure that did not result in an ostomy. Quantitative and qualitative
      data on sexual functioning, relationships, and other dimensions of HR-QOL were
      collected using the modified City of Hope Quality of Life-Ostomy questionnaire.
      RESULTS: The overall response rate was 49%. Prevalence of erectile dysfunction
      was significantly higher among ostomates compared with controls (P < .001).
      Although a greater proportion of veterans with ostomies reported being sexually
      active before surgery compared with controls (P < .001), the proportion of men
      who had resumed sexual activity after surgery is significantly lower among the
      ostomy group (P = .015). Compared with veterans with ostomies who did not resume
      sexual activity after surgery, those who were sexually active reported a higher
      total HR-QOL score and higher scores on all 4 modified City of Hope Quality of
      Life-Ostomy dimensions (psychological, social, physical, and spiritual well
      being). Veterans with ostomies who had resumed sexual activity after their ostomy
      also reported that their ostomy had caused significantly less interference with
      social activities, less isolation, less interference with their personal
      relationships, and less interference with their ability to be intimate. These men
      also reported less difficulty adjusting to the ostomy. Results of qualitative
      analyses showed that problems with intimacy and sexual function are among the
      greatest challenges faced by ostomates. CONCLUSION: Presence of an ostomy was
      associated with lower rates of sexual activity and higher erectile dysfunction.
      The lower rates of sexual activity and sexual satisfaction were related to the
      social and psychological dimensions of HR-QOL among men with ostomies.
      Interventions to address sexual concerns of male ostomates and their partners may
      prevent decrements to HR-QOL for these patients. IMPLICATIONS FOR PRACTICE:
      Results of the study have implications for the clinical nurse specialist role in
      supporting and educating patients with ostomies to minimize the negative impact
      of an intestinal ostomy on sexual health and HR-QOL. Implications also relate to
      the need to educate current and future nurses about the importance of assessing
      sexual health.

PMID- 18091128
TI  - Clinical nurse specialist profile: Nancy M. Albert. Interview by Jo Ellen Rust.

PMID- 18091129
TI  - The human factor.

PMID- 18091132
TI  - Foreword.

PMID- 18091133
TI  - Population-based register of stroke: manual of operations.
AB  - Cardiovascular disease is the leading cause of death and hospitalization in both
      sexes in nearly all countries of Europe. The main forms of cardiovascular disease
      are ischaemic heart disease and stroke. Stroke by itself is the second leading
      cause of death in the European Union, and the annual number of cases of stroke is
      expected to increase within the next few decades, mainly owing to a growth in the
      proportion of older people. Stroke is an expensive disease because of the large
      number of premature deaths, ongoing disability in survivors, and the impact on
      families or caregivers and on health services (treatment and rehabilitation).
      Therefore, there is a pressing need to make stroke prevention and treatment a
      priority, to reduce the growing health burden and lessen its socioeconomic
      impact. The magnitude of the problem contrasts with the shortage, weak quality,
      and comparability of data available in most European countries. A stepwise
      surveillance procedure based on standardized data collection, appropriate record
      linkage, and validation methods was set up by the EUROCISS project (EUROpean
      Cardiovascular Indicators Surveillance Set), to build up comparable and reliable
      indicators for the surveillance of stroke at the population level.This manual of
      operations is intended for health professionals and policy makers. It provides a
      standardized and simple model for the implementation of a population-based
      register, which can provide estimates of attack rate and case fatality. The
      manual recommends starting from a minimum data set. Before implementing a
      population-based register, it is important to identify the target population
      under surveillance, which should preferably cover a well defined geographical and
      administrative area or region representative of the whole country, where
      population data and vital statistics (mortality and hospital discharge records at
      least) are routinely collected and easily available each year. All cases among
      residents should be recorded even if the case occurs outside the area. Validation
      of a sample of fatal and nonfatal events is mandatory.

PMID- 18091135
TI  - Cardiovascular surveys: manual of operations.
AB  - Cardiovascular disease (CVD) is the leading cause of death and hospitalization in
      both men and women in nearly all countries of Europe. The most frequent forms of
      CVD are those of an atherosclerotic origin, mainly ischaemic heart disease,
      stroke and heart failure. The magnitude of the problem contrasts with the usual
      paucity and poor quality of data available on incidence and prevalence of CVD,
      except for few rigorous but limited studies. The objectives of the health
      interview and health examination surveys (HIS/HES) are to evaluate the frequency
      and the distribution of the disease, to evaluate trends and treatment
      effectiveness, to estimate risk factors distribution and prevalence of high risk
      conditions and to monitor prevention programmes. According to the EUROCISS
      project (EUROpean Cardiovascular Surveillance Set) recommendations, surveys are
      aimed at describing the prevalence of the following CVD conditions: myocardial
      infarction, heart failure, angina pectoris, peripheral arterial disease, stroke,
      and ischaemic heart disease.HIS and HES were developed to supplement information
      collected from routine databases and population-based registers to implement
      consistent public health policies. HIS can be repeated periodically in a new
      sample of the population, or can follow up over time the population recruited at
      baseline. Procedures and methods to collect information from participants include
      self-administered questionnaires, direct interviewer-administered questions and
      telephone interviews. A minimum set of questions to be administered every year,
      along with a longer, more detailed module to be administered periodically are
      recommended to evaluate CVD prevalence. The addition of HES provides more
      detailed and objective information that can be used to improve estimates
      regarding prevalence of both risk factors and disease status. The selection of
      more specialized CVD-specific tests will depend on the objective the survey is
      designed to achieve, the assumed response rate and the cost and time
      considerations. For HES on CVD the minimum required is to perform the following
      measurements: height, weight, blood pressure, waist circumference, total and high
      density lipoprotein-cholesterol and glucose assay in a nonfasting blood sample.
      The next appropriate step would be to perform an electrocardiogram. High costs
      usually make HES difficult to carry out. Standardization of measurements,
      training of personnel and quality control are essential to assure reliable data.
      A high response rate is extremely important, as nonrespondents tend to have
      different health characteristics from the rest of the sample and their omission
      therefore results in bias. This manual of operations is intended for health
      professionals and policy makers and provides a standardized and simple model for
      the implementation of a CVD survey.

PMID- 18091134
TI  - Population-based register of acute myocardial infarction: manual of operations.
AB  - Cardiovascular disease is the leading cause of death and hospitalization in both
      sexes in nearly all countries of Europe. The main forms of cardiovascular disease
      are ischaemic heart disease and stroke. The magnitude of the problem contrasts
      with the shortage, weak quality and comparability of data available in most
      European countries. Innovations in medical, invasive and biological treatments
      have substantially contributed to the escalating costs of health services. It is
      therefore urgent to obtain reliable information on the magnitude and distribution
      of the disease for both adequate health planning (including preventive
      strategies) and clinical decision making with correct cost-benefit assessments.A
      stepwise surveillance procedure based on standardized data collection,
      appropriate record linkage and validation methods was set up by the EUROCISS
      Project (EUROpean Cardiovascular Indicators Surveillance Set) to build up
      comparable and reliable indicators (attack rate and case fatality) for the
      surveillance of acute myocardial infarction/acute coronary syndrome at population
      level. This manual of operations is intended for health professionals and policy
      makers and provides a standardized and simple model for the implementation of a
      population-based register. It recommends to start from a minimum data set and
      then follow a stepwise procedure. Before implementing a population-based
      register, it is important to identify the target population under surveillance
      which should preferably cover a well-defined geographical and administrative area
      or region representative of the whole country for which population data and vital
      statistics (mortality and hospital discharge records at minimum) are routinely
      collected and easily available each year. All cases among residents should be
      recorded even if the case occurs outside the area. Validation of a sample of
      fatal and nonfatal events is mandatory.

PMID- 18091137
TI  - The challenges of studying childhood sexual abuse among adolescent mothers.
AB  - Sexual abuse researchers are faced with many challenges. This article begins with
      a discussion of the theoretical underpinnings of topic sensitivity and describes
      difficulties specific to the study of childhood sexual abuse among adolescent
      mothers. In the last part of this article, suggestions for diminishing the
      difficulties and factors to consider when planning future studies are discussed.
      The aim of this article is to prepare novice researchers for the challenges that
      may occur while studying childhood sexual abuse among adolescent mothers and
      provide them with solutions to consider when they encounter such challenges.

PMID- 18091139
TI  - Advances in understanding and treating childhood sexual abuse: implications for
      research and policy.
AB  - Childhood sexual abuse is a major public health problem affecting thousands of
      children and adolescents in the United States each year. For more than 20 years,
      researchers, healthcare professionals, and policymakers have had considerable
      disagreements about various aspects of child sexual abuse. Although everyone
      agrees that sexual abuse is a harmful thing for children to experience, there is
      a lack of consensus on a definition of sexual abuse, investigation of
      allegations, long-term consequences, what constitutes appropriate psychotherapy,
      and what public health policies should be developed to prevent sexual abuse. The
      purpose of this article is to explore advances that have been made in
      understanding and treating child sexual abuse, to look at the implications for
      further research, and to address the public health policies that exist for
      preventing child sexual abuse.

PMID- 18091140
TI  - Nurturing hostile environments: the problem of school violence.
AB  - Although school violence directly affects the overall health and well-being of
      children and adolescents, clear priorities have not been identified for dealing
      with the problem. Horrific events such as the 1999 Columbine High School shooting
      in Littleton, Colo, and recent shootings at Virginia Tech have focused the nation
      on high-profile, media-worthy school violence to the detriment of addressing
      everyday forms of violence in schools. Policies that have been developed to
      reduce school violence have mixed reviews. To raise the consciousness of
      healthcare professionals, educators, legislators, and the general public, the
      most salient issues are discussed.

PMID- 18091141
TI  - Caring for and connecting with homeless adolescents.
AB  - Adolescents from a variety of backgrounds are among the growing number of
      homeless Americans. Although they lack maturity and various skills, they manage
      to survive in dangerous and stressful environments. This article asserts that
      social policy that leads to services such as housing, education, and healthcare
      should be based on a philosophy, ethic, and theory of caring and connectedness,
      which have been shown to protect adolescents as they mature. The article includes
      brief descriptions of theories of caring, pathways to homelessness for
      adolescents, survival needs of homeless youth, and characteristics of service
      programs that incorporate caring and connectedness.

PMID- 18091142
TI  - Res ipsa loquitur: "the thing speaks for itself": so why isn't evidence enough
      for enactment?
AB  - The gap between scientific evidence and its application poses profound challenges
      to adolescent healthcare researchers, educators, and advocates. These challenges
      are compounded by the alliance of political power with social and religious
      ideology, the consequence of which is the distortion and undermining of
      scientific evidence and inquiry. This article, based on a keynote presentation to
      the Center for Health Promotion Research Conference on Adolescent Health,
      describes examples of such interference and the need for effective response to
      those who deliberately seek to widen the gap between evidence-based approaches to
      adolescent health, as well as the implementation of such knowledge in programs
      and policy.

PMID- 18091143
TI  - Making drug and alcohol prevention relevant: adapting evidence-based curricula to
      unique adolescent cultures.
AB  - There is profound value in involving youth in the cultural adaptation of evidence
      based drug prevention curricula. Presently, despite the existence of evidence
      based programs, few community settings are aware of, utilizing, and following
      evidence-based curricula in practice. Therefore, to transfer such programs to
      practice, systematic adaptation procedures should be further developed, utilized,
      and evaluated. It is recommended that community settings adapt curricula to meet
      their youths' unique needs to be effective, particularly with diverse cultures.

PMID- 18091144
TI  - Promoting healthy development among survivors of adolescent cancer.
AB  - Cancer-surviving adolescents face significant health challenges including both
      physical and psychological late effects as they transition to young adulthood. A
      cancer diagnosis during adolescence, a time of social independence and increased
      personal decision making, can cause significant social and emotional struggles
      that may impair the ability of the adolescent to make health-promoting decisions
      and avoid risky behaviors such as substance use. This article reports on the
      little studied experiences of adolescents who have survived cancer with a focus
      on developing programs and policies that address their health-promotion needs in
      both community and survivorship clinics.

PMID- 18091145
TI  - Peer relations, adolescent behavior, and public health research and practice.
AB  - Peer relations are central to adolescent life and, therefore, are crucial to
      understanding adolescents' engagement in various behaviors. In recent years,
      public health research has increasingly devoted attention to the implications of
      peer relations for the kinds of adolescent behaviors that have a direct impact on
      health. This article advocates for a continuation of this trend. With this aim,
      we highlight key themes in the rich literature on the general developmental
      significance of adolescent-peer relations, provide an overview of how these
      themes have been incorporated into public health research and practice, and
      suggest future avenues for peer-focused public health research that can inform
      adolescent health promotion in the United States.

PMID- 18091146
TI  - Patterns of attachment organization, social connectedness, and substance use in a
      sample of older homeless adolescents: preliminary findings.
AB  - Social researchers continue to strive to understand the development and social
      decision-making processes of homeless adolescents. While it has been established
      that attachment is a salient factor with regard to childhood maltreatment and
      later psychosocial problems, there is a dearth of information on how homeless
      youths' thoughts and feelings about attachment may also be linked to behavioral
      risks including alcohol and substance use. This exploratory study examines older
      homeless adolescent's perspectives on attachment, trauma, and substance use via
      the semistructured Adult Attachment Interview and survey data. The findings
      illuminate the relationship between these factors and implications for future
      research and work with this population.

PMID- 18091147
TI  - Cancer risk in nuclear workers occupationally exposed to uranium-emphasis on
      internal exposure.
AB  - Workers involved in the nuclear fuel cycle have a potential for internal exposure
      to uranium. The present review of epidemiological studies of these workers aims
      to elucidate the relationship between occupational internal uranium exposure and
      cancer risk. Eighteen cohort and 5 nested case-control studies published since
      1980 are reviewed. Workers occupationally exposed to uranium appear to be at
      increased risk of mortality from neoplasms of the lung, larynx, and lymphatic and
      haematopoietic tissue. Currently available evidence for a positive association
      between internal exposure to uranium and the risk of cancer is limited. The
      common weaknesses in reviewed studies include low statistical power and
      inaccurate assessment of internal exposure to uranium. Further investigations
      should focus on precise assessment of occupational exposure and address the issue
      of potential confounders.

PMID- 18091148
TI  - Freundlich and dual Langmuir isotherm models for predicting 137Cs binding on
      Savannah River Site soils.
AB  - Distribution of 137Cs and stable cesium between aqueous solution and near-surface
      soil samples from five locations at the Savannah River Site was measured in order
      to develop a predictive model for 137Cs uptake by the soils. Sorption of 137Cs in
      these soils appears to be mostly by hydroxy-interlayered vermiculite. Batch
      sorption studies with 4 d for equilibration were conducted at three cesium
      concentrations and at two backing electrolyte (NaNO3) concentrations. The soil
      solution mixtures were pH-adjusted to evaluate the effects of pH on cesium
      sorption. Sorbed cesium was related to the equilibrium aqueous cesium
      concentrations by a Freundlich isotherm model. Model fits on logarithmic scales
      have a common slope of 0.60 +/- 0.03 for acidic mixtures and 0.69 +/- 0.04 for
      neutralized mixtures but have unique intercepts that are influenced by backing
      electrolyte concentration and pH. An ion-exchange model is proposed that pertains
      to all five soils and relates the Freundlich isotherms to the cation exchange
      capacity of soil and the aqueous concentrations of cesium, sodium, and a third
      ionic species that was hydrogen in the acidic mixtures and potassium in the
      neutralized mixtures. Model fits are consistent with Kd values in the entire
      range of 5-2,300 L kg(-1) determined for the five soil types. As an alternate
      model, dual Langmuir isotherms were fitted to the data. The results suggest
      cesium sorption by (1) relatively few interlayer-wedge sites, highly selective
      for cesium, and (2) much more abundant but less selective sites on internal and
      external planar surfaces.

PMID- 18091149
TI  - Modeling gamma radiation dose in dwellings due to building materials.
AB  - A model is presented that calculates the absorbed dose rate in air of gamma
      radiation emitted by building materials in a rectangular body construction. The
      basis for these calculations is formed by a fixed set of specific absorbed dose
      rates (the dose rate per Bq kg(-1) 238U, 232Th, and 40K), as determined for a
      standard geometry with the dimensions 4 x 5 x 2.8 m3. Using the computer codes
      Marmer and MicroShield, correction factors are assessed that quantify the
      influence of several room and material related parameters on the specific
      absorbed dose rates. The investigated parameters are the position in the
      construction; the thickness, density, and dimensions of the construction parts;
      the contribution from the outer leave; the presence of doors and windows; the
      attenuation by internal partition walls; the contribution from building materials
      present in adjacent rooms; and the effect of non-equilibrium due to 222Rn
      exhalation. To verify the precision, the proposed method is applied to three
      Dutch reference dwellings, i.e., a row house, a coupled house, and a gallery
      apartment. The averaged difference with MCNP calculations is found to be 4%.

PMID- 18091150
TI  - Determination of natural radionuclides content in some building materials in
      Nigeria by gamma-ray spectrometry.
AB  - This paper presents the findings of a study undertaken to determine the natural
      radioactivity present in some building materials in Nigeria using a gamma-ray
      spectrometer with a hyper pure germanium detector. A total of 118 samples of
      commonly used building materials were collected from manufacturers and suppliers
      of these materials. The mean radioactivity concentrations measured in the
      different building materials varied from 9.4 to 62.9, 1.3 to 88.4, and 21.5 to
      762.4 Bq kg(-1), respectively, for 226Ra, 232Th, and 40K. The average contents of
      226Ra, 232Th, and 40K for all the samples were 36.3, 46.5, and 320.9 Bq kg(-1),
      respectively, lower than the world average for building materials (50, 50, and
      500 Bq kg(-1)). The calculated mean radium equivalent activity and external and
      internal hazard indices for the entire sample were lower than United Nation
      Scientific Committee on the Effects of Atomic Radiation recommended limits and
      comparable with results of similar studies undertaken in other countries. The
      mean annual gonadal equivalent doses of some of the samples were higher than the
      world average value for soil.

PMID- 18091151
TI  - Indoor radon in Kuwait.
AB  - Indoor radon measurements were carried out in 300 dwellings in Kuwait using
      duplicate sets of charcoal detectors. Measurements were made at three different
      locations in the dwellings: living rooms, bedrooms, and basements. The results
      show that the radon concentration in the dwellings of Kuwait was found to vary in
      the range of 4.0-241.8 Bq m(-3) with a mean value of 32.8 Bq m(-3), and most
      values are confined within the range of 10-50 Bq m(-3) for all locations with few
      cases above the value of 100 Bq m(-3). Overall results show that the indoor radon
      concentration levels in Kuwait are relatively low, which is attributed to the use
      of air conditioning in summer and possible natural ventilation in winter. The
      radon concentration in basements was found to be relatively higher when compared
      to other rooms of the dwellings.

PMID- 18091152
TI  - Measurements of ELF electromagnetic exposure of the general public from Belgian
      power distribution substations.
AB  - In this paper, the exposure of the general public due to distribution substations
      of 11/0.22-0.4 kV is investigated. The substations are categorized according to
      their location (substations in buildings, detached substations, substations
      between two houses, and underground substations in the pavement), and eight
      relevant substations are selected to perform measurements of the electromagnetic
      fields. The purpose of this paper is to determine the "minimum distances" for the
      general public--defined as the distances outside which the field levels do not
      exceed a certain field value--of these substations. In total, 637 field
      measurements were performed: 358 measurements of the magnetic field and 279
      measurements of the electric field in different locations. Measured momentary
      magnetic field values are within the range of 0.025 to 47.39 microT. Electric
      fields are within the range 0.1 to 536 V m(-1). Also, magnetic field measurements
      as a function of the height above the ground were performed. The maximal magnetic
      (values over one day) and electric fields for all the investigated substations
      were below 100 microT and 5 kV m(-1), respectively. For exposure over a year, all
      substations except one delivered values below 100 microT. For the substation
      producing a magnetic field above 100 microT, a minimum distance of about 0.5 m
      was obtained. When comparing the average exposure with the value of 0.4 microT,
      minimum distances of maximally 5.4 m (average day) and 7.2 m (average year) were
      obtained.

PMID- 18091153
TI  - Safety devices for delivery of radioactive iodine.
AB  - For clinical applications, liquid 131I is more cost-effective and flexible than
      capsules for diagnostic and therapeutic dosing of the thyroid gland. However, the
      liquid is potentially a contamination hazard because of possible spilling by a
      patient or staff member. The objective of this study was to design a safety
      system for delivering therapeutic doses of liquid 131I that would not only
      minimize potential contamination spill hazards but also reduce radiation exposure
      to patients and staff during the therapeutic dosing process. A plastic vial with
      a secured top and tube to allow drinking was placed in a lead container with a
      screw-on lid. A dosing tray holds the lead-encased vial directly in front of the
      patient, further reducing the risk of spillage. The tray has a peripheral lip to
      contain any liquid that might spill. This height-adjustable tray is temporarily
      fastened to the chair's armrest. After the dose is administered, 20 mL of
      distilled water is injected into the shielded vial through a 1.5-mm orifice in
      the cap. The orifice is a vent to eliminate any vacuum created while drinking.
      The water rinses the vial so the patient receives the entire dose after the
      second drink. Our shielded spill-proof safety cup effectively seals the contents,
      reducing the risk of spillage and minimizing radiation exposure to patients and
      staff. Impact testing demonstrated only minimal leakage when the cup was dropped
      from a 1-m height. Our shielded cup and tray assembly could be implemented
      efficiently and economically into the clinical setting with minimal expense.

PMID- 18091154
TI  - A 3He counter version of the Thermo Fisher Scientific NRD neutron rem meter.
AB  - Thermo Fisher Scientific's NRD rem meter has been in production for almost 40 y
      and is the primary rem meter in use at many U.S. Department of Energy facilities.
      An upgrade project was initiated at the Los Alamos National Laboratory with the
      primary goal of increasing the NRD's neutron sensitivity through the substitution
      of pressurized 3He gas (4 atmospheres) for the stock counter tube's BF3 fill gas.
      Historically, BF3 counters were far less expensive relative to 3He and were
      usually chosen on the basis of cost. That is no longer the case, with pricing for
      both types of counters being similar. Test results have shown that the 3He
      counter version of the NRD exhibits stable operation at a reasonable bias voltage
      and good gamma rejection. Sensitivity has been increased by about a factor of
      four with no penalty in cost.

PMID- 18091155
TI  - AGHCF gaseous-effluent tritium sampling system: design considerations and
      performance testing results.
AB  - Performance testing results involving the operation of a gaseous-effluent tritium
      sampling system are provided. A system description, including design improvements
      made over the course of several years of operation, is also presented. The
      sampling technique is based on using ethylene glycol bubblers for collecting
      tritiated water entrained as vapor in a nitrogen purge gas from a hot cell
      facility. Tritiated gas is converted to water vapor using a high temperature
      copper oxide bed; newly-formed water molecules are readily collected in a second
      set of ethylene glycol bubblers. For a single bubbler containing 20 mL of
      ethylene glycol, the tritium collection efficiency was determined to be 98.3%. To
      optimize performance and to minimize the volume of mixed waste generated, tests
      were performed to evaluate variations in the collection efficiency as a function
      of sorbent volume. For purposes of comparison the performance of water-filled
      bubblers was also evaluated. With two water bubblers connected in series the
      overall collection efficiency was quite satisfactory at 95.4%, although
      appreciable water losses were evident. The bed oxidation efficiency for tritiated
      gas was evaluated over a range of temperatures; at a catalyst bed temperature of
      350 degrees C nearly all the gas was converted to water vapor. System memory
      effects were assessed by measuring the amount of residual contamination present
      in the bubblers after purging the sampling system for a week offline.
      Contamination problems arising from previous sampling periods were
      inconsequential. The overall uncertainty associated with the total quantity of
      tritium discharged to the environment based on the results of the performance
      testing was estimated to be +/-24% at the 95% confidence level.

PMID- 18091156
TI  - Comment on poisson-based detection limit and signal confidence intervals for few
      total counts.

PMID- 18091158
TI  - No excuses: continuing education.

PMID- 18091159
TI  - Implant.

PMID- 18091160
TI  - Bone block allograft impregnated with bone marrow aspirate.
AB  - PURPOSE: To evaluate the influence of bone marrow aspirate when added to bone
      block allograft to repair osseous defects. BACKGROUND: Bone-marrow aspirate has
      been combined with xenograft and allograft particulate material and has produced
      a significant quantity of new bone growth. However, the use of allograft bone
      blocks has advantages in some clinical situations. This article discusses cell
      based therapies by means of in vivo transplantation of stem cells derived from
      bone-marrow aspirate and incorporated into allograft corticocancellous bone block
      for bone regeneration. MATERIALS: A technique for combining bone-marrow aspirate
      with block allografts was developed. To evaluate its influence in repairing
      osseous defects, a maximum of 3 to 4 mL of bone marrow was aspirated from the
      anterior iliac crest of 5 patients who had severely atrophic maxillary and
      mandibular ridges. Five sites were grafted with allograft bone blocks saturated
      with bone-marrow aspirate and secured with bone screws (ACE Surgical Supply
      Company, Inc. Brockton, MA). At one of the sites a core specimen was taken 4
      months after implant placement and submitted for standard histologic and
      histomorphometric analysis. RESULTS: After 4 to 8 months of healing, all the
      grafts had integrated into the recipient bone. Implants were placed at all 5
      sites and osseointegrated successfully. Examination of the bone core showed the
      graft to be well-integrated, with 54% of the core consisting of bone and 46% of
      marrow. Eighty-nine percent of the bone was vital. CONCLUSION: Impregnation of
      bone-marrow aspirate into allograft bone block activates the body's ability to
      form new bone. The bone-marrow aspiration technique is less invasive than
      harvesting autogenous bone from a second surgical site, offers predictable
      results, and is cost effective.

PMID- 18091161
TI  - Common implant esthetic complications.
AB  - Today, osseointegration of implants is readily attainable with high long-term
      survival rates. Consequently, clinicians are now focusing on improving implant
      esthetics and are starting to incorporate this parameter into their definition of
      implant success. However, studies measuring factors that affect implant esthetics
      and implant esthetic outcomes are lacking in the literature. A satisfactory
      esthetic outcome requires the clinician to be aware of the different factors
      affecting esthetics during the preplanning, surgical, and prosthetic phases of
      implant placement. This article addresses the etiologies of esthetic
      complications during each of these 3 phases and provides preventive and
      corrective treatment suggestions for these situations.

PMID- 18091162
TI  - Implant rehabilitation of central incisor: a staged approach.
AB  - The aim of this report is to demonstrate the outcome of implant rehabilitation in
      the anterior maxilla. Aesthetics in implantology results from the correct
      execution of many rehabilitation phases: presurgical planning, surgical and
      prosthetic phases, and case management. In the presurgical phase, preexisting
      anatomical conditions and prosthetic evaluations influence the choice of
      regenerative techniques. Correct presurgical planning, in order to realize
      surgical and prosthetic procedures, is the most important phase to obtain an
      aesthetic result. Only a successful anatomical correction of hard and soft
      tissues is able to assure a satisfying therapeutic achievement involving many
      operative steps and the rigorous observance of recovery timing. A guided bone
      regeneration technique with a staged approach was used in conjunction with
      implant replacement.

PMID- 18091163
TI  - Calvarial bone grafts in severe maxillary atrophy: preprosthetic surgery with
      sedation.
AB  - PURPOSE: This is a technique report of cranial bone harvesting for severe
      maxillary atrophy without general anesthesia. MATERIALS: A patient of Class VI by
      Cawood and Howell underwent 2 extensive bilateral sinus lifts with 5 cortical
      blocks with sedation only. RESULTS: The reconstruction made possible the
      placement of 8 Branemark implants. The operation was performed as a day-hospital
      with a faster clinical and social recovery. CONCLUSIONS: This technique, by
      avoiding general anesthesia, makes calvarial bone grafting more comfortable for
      the patient and comparable to an intraoral harvest with less complications.

PMID- 18091164
TI  - Dental implants in geriatric patients: a retrospective study of 47 cases.
AB  - PURPOSE: To determine the overall success of dental implants placed in geriatric
      patients. PATIENTS: Dental implants were placed in 47 geriatric patients who were
      79 or more years of age at the time of the procedure. The study group was
      composed of 27 men and 20 women, with a median age of 89 years and a range of 79
      to 99 years of age at the time of implant surgery. A total of 73 dental implants
      were placed in the maxilla and 87 dental implants placed in the mandible. All
      implants were restored with fixed implant-supported prostheses or removable
      implant-supported prostheses. Eleven of the patients underwent maxillary sinus
      augmentation with porous hydroxyapatite and platelet-rich plasma. Seven patients
      had their implants immediately loaded. RESULTS: A total of 160 dental implants
      were placed in the 47 geriatric patients. One hundred fifty-nine integrated
      successfully. In the case of the failed implant, the site was grafted and another
      implant was placed 5 months subsequent to the initial failure. This replacement
      implant integrated and has been in function for 6 months. The survival rate for
      dental implants placed in the maxilla was 99% and in the mandible was 100% in our
      geriatric population. CONCLUSION: Treatment with dental implants can be
      predictable and safe for the rapidly growing geriatric population. Geriatric
      patients who are medically stable are suitable candidates for osseointegrated
      implant surgery, which facilitates oral function, comfort, and quality of life. A
      review of the 47 geriatric patients treated supports the conclusion that dental
      implants can be successfully placed and restored with fixed implant-supported or
      removable implant-supported prostheses.

PMID- 18091165
TI  - Report of 1633 implants in 814 augmented sinus areas in function for up to 180
      months.
AB  - PURPOSE: The long-term success of implants functioning in sinuses augmented with
      a variety of materials were evaluated in 2 private practices. MATERIALS:
      Treatment outcomes of 1814 augmented sinuses, and subsequent placement of 1633
      implants into 763 augmented sinuses, were assessed through clinical and
      radiographic examinations in 2 private practices. Statistical analysis was
      carried out utilizing the analysis of variance method and step-wise linear
      regression at P < 0.001. RESULTS: Eight hundred fourteen sinus augmentation
      procedures were performed. Eight hundred six sinus augmentation procedures were
      deemed successful (99.0%), as defined by implants functioning successfully in the
      augmented sinus areas. A variety of augmentation materials were utilized to
      effect sinus augmentation. Of the 1633 implants placed in augmented sinuses, 1613
      were functioning successfully, yielding an accumulate success rate and function
      of 98.1%. The mean implant time in function was 69.1 months. The longest
      functioning implants had been in function for 180 months. DISCUSSION: The
      results, from 2 private offices in conjunction with numerous restorative
      clinicians, utilizing a variety of augmentation materials and implants, were
      comparable to those reported by other authors. The clinical predictability of
      sinus augmentation therapy and of implants functioning in augmented sinuses were
      reinforced. CONCLUSION: Predictable sinus augmentation therapy may be obtained
      through the use of a variety of regenerative materials. Titanium implants of
      various configurations and surface topographies will function successfully in
      augmented sinuses over time.

PMID- 18091166
TI  - In vitro evaluation of thermomechanic coupling in conical implant-to-abutment
      joint.
AB  - PURPOSE: This study investigates the use of thermomechanic abutment-to-implant
      coupling. MATERIALS AND METHODS: Ten 3.5 x 1 mm commercially pure titanium
      Ankylos implants (Dentsply Friadent, Mannheim, Germany) and 10 standard abutment
      of titanium alloy Ti6Al4V were used in the present study. All fixtures were
      mounted on hold specimen provided of a 10-ohm electrical resistance to maintain
      the fixture at 37 degrees C +/- 3 degrees C during the entire test and to
      evaluate the influence of the coefficient of thermal expansion on joined conical
      abutment. The threading part of all abutments was cut off using a diamond disc.
      All abutment implants were coupled at 35 N using a universal testing machine
      (Lloyd 30K, Lloyd Instruments Ltd. Segensworth, UK). Five abutments were heated
      at 37 degrees C +/- 3 degrees C, whereas the reaming were cooled at 0 degrees C
      +/- 3 degrees C before connection. To measure the difference a pull-out test was
      performed. RESULTS: The results were statistically analyzed using unpaired t test
      at P < 0.05. The cooled specimens showed a result (mean +/- SD) of 421.6 +/-
      55.20 N, whereas for heated specimens the result was 238.4 +/- 42.27 N. The
      difference was statistically significant (P = 0.001). CONCLUSIONS: The
      thermomechanic coupling significantly increases the performance of the conical
      joint.

PMID- 18091167
TI  - Effects of surface conditioning on the retentiveness of titanium crowns over
      short implant abutments.
AB  - PURPOSE: The integrity and retention of cemented restorations over implant
      abutments is difficult to achieve when the axial wall height of the abutment is
      short. PURPOSE: : To compare the effect of different surface conditions on the
      retentiveness of titanium crowns cemented over short (3 mm) ITI solid abutments
      using 2 types of cement. Surface pretreatment included sandblasting, silicoating,
      and application of alloy primer. METHODS AND MATERIALS: Forty-eight ITI implants
      and solid abutments 5.5 mm in height were divided into six groups. The axial
      height of abutments in group I was unaltered to serve as a control. The remaining
      abutments in (groups II-VI) were reduced to a 3-mm height. Groups I and II were
      luted with ZnPO4 cement without any surface pretreatment. In groups III and IV,
      the fit surface of the castings and solid abutments were sandblasted, before
      luting, with ZnPO4 or Panavia 21, respectively. In group V castings and abutments
      were sandblasted, pretreated with Siloc Bond, and luted with Panavia 21. In group
      VI castings and abutments were sandblasted, pretreated with alloy primer, and
      luted with Panavia 21. Crown retention was measured using a universal testing
      machine after 1 week of storage in water at 37 degrees C. RESULTS: Analysis of
      variance revealed a highly significant difference among the groups. Sandblasted
      castings and abutments pretreated with alloy primer or Siloc Bond before luting
      with Paravia 21 resin cement exhibited the greatest retentive strength (P <
      0.05). Castings luted with zinc phosphate over short ITI solid abutment exhibited
      the lowest retention (P < 0.05). CONCLUSION: The retention of titanium castings
      luted over ITI solid abutments was influenced by axial height, surface texture,
      surface pretreatment, and type of cement. Phosphoric alloy primer is more
      effective and less technique sensitive than the Siloc Bond with regard to
      retention enhancement of titanium castings over short ITI solid abutment.

PMID- 18091168
TI  - Salivary pH in edentulous patients before and after wearing conventional dentures
      and implant overdentures: a clinical study.
AB  - PURPOSE: Objective of this prospective study were to point out the changes of pH
      of resting saliva before and after prosthetic treatment in implant denture
      wearers. MATERIALS AND METHODS: The study sample comprised 2 groups of edentulous
      patients, ranging in age from 50 to 80, who had not worn complete dentures in the
      past. First group was composed of 60 patients, who were planned for complete
      denture treatment. Second group consisted of 15 patients, who were planned for
      implant dentures treatment. Two measurements of pH of unstimulated saliva were
      carried out for each person. The salivary pH was measured before the construction
      of complete dentures and 15 days after the insertion. The measurements of pH of
      saliva were made using Electro pH meter-CONSORT-P903 (Scientific Instruments Co.,
      Milan, Italy). RESULTS: Data were statistically analyzed by t test for paired
      observations. The outcome of this study showed, significant statistical
      differences on the values of saliva's pH 15 days after the insertion of complete
      dentures and dentures supported by implants (P < 0.001). CONCLUSIONS: Within the
      limitations of this study, changes of salivary pH were found after the insertion
      of conventional dentures and dentures supported by implants.

PMID- 18091169
TI  - Failing factors associated with osseointegrated dental implant loss.
AB  - PURPOSE: Dental implants are currently the aesthetic and functional alternative
      for tooth replacement. Despite the high success rate shown by longitudinal
      studies, failures do occur, even in patients who present appropriate clinical
      conditions. The aim of the present study was to identify factors related to, or
      determinant of, dental implant loss in patients of the Latin-American Dental
      Research Institute, Curitiba, PR, Brazil. MATERIALS AND METHODS: Retrospective
      analysis of 3578 records of patients who had implants placed in this institute
      during the period of 1996 to 2006 was performed. Beyond records, panoramic and
      periapical radiographs were analyzed. RESULTS: Of the 3578 individuals implant
      treated, failures occurred in 126 (3.5%) patients (mean age 52.2 +/- 10.6 years).
      Men lost more implants (4.5%) than did women (3.1%) (P = 0.05). Most failure
      occurred before loading (88.2%). Failure was more frequent when the implant was
      installed in the posterior jaw (58.5%). The main detectable causes of implant
      loss were evaluated. Most implant losses (75%) did not have an apparent clinical
      cause. Identified causes were 17.5% iatrogenic conditions (surgical technique,
      contamination, and/or occlusal trauma), poor bone quality and quantity (3%), peri
      implantitis (1%), and 3.5% missing data. CONCLUSIONS: The results obtained in
      this study suggest that host factors can be contributing to the failure of
      implants.

PMID- 18091170
TI  - Autogenous bone graft associated with enamel matrix proteins in bone repair.
AB  - PURPOSE: Autogenous bone has been used with success as implants in intrabony
      defects, because of its biological advantages and osteogenic potential. The
      objective of this study was to evaluate histological and histometrically the bony
      repair in intrabony defects after dental extractions in rats with graft of a
      combination of the enamel matrix protein (EMP) (Emdogain, Strauman USA, LLC,
      Andover, MA. Headquarters in Basel, Switzerland) and autogenous bone. MATERIALS
      AND METHODS: Male rats (Rattus norvegicus, Wistar variety) weighing from 250 to
      300 g were anesthetized and submitted to the extraction of the superior incisive
      and divided in (a) group with autogenous bone (fragment of bone of the alveolar
      ridge was grafted inside the alveolus) and (b) group with autogenous bone
      associated with EMP. The animals were killed on the 7th, 21st, and 42nd day after
      the extraction. The maxillae were processed to obtain fine sections (5 microm)
      stained with hematoxylin-eosin. The percentual volume of bone tissue in
      contiguous areas of the graft was calculated through a counting point system of
      image. RESULTS: The results showed that the bone fragments grafted in the
      cervical third of the alveolus developed a progressive osseointegration without
      foreign-body reaction. The quantification of the bony repair in the areas
      adjacent to the graft showed that the autogenous bone associated with EMP
      produced a greater amount of bone (10%-15% by analysis of variance, P = 0.05) in
      all the studied periods. CONCLUSIONS: It was concluded that the autogenous bone
      associated with EMP grafted in bony defects, immediately after the dental
      extraction in rats, demonstrated biocompatibility and accelerated the repair of
      bone defect.

PMID- 18091171
TI  - The effect of different mandibular dentures on antagonistic maxillary ridge.
AB  - PURPOSE: Is to evaluate the antagonistic, maxillary ridge resorption for
      different prosthetic modalities mainly mucosa-supported mandibular complete
      overdentures, combined mucosa implant-supported mandibular complete overdenture,
      and lower conventional complete dentures. MATERIALS AND METHODS: Fifteen
      completely edentulous patients were divided into 3 groups; 5 patients each. Group
      I patients received maxillary conventional denture and mandibular overdentures
      retained by magnet attachment on 2 implants (mainly mucosa-supported
      overdenture). Group II patients received maxillary conventional denture and
      mandibular overdentures retained by bar attachment on 2 implants (combined mucosa
      implant-supported overdenture). Group III patients received upper and lower
      conventional complete denture. All patients were evaluated clinically and
      radiographically immediately after insertion and after 1 and 2 years. Panoramic
      radiographic film was used to evaluate the antagonistic maxillary ridge
      resorption. RESULTS: Indicated a more pronounced annual bone resorption of the
      antagonistic maxillary ridge after 2 years in patients with conventional complete
      denture wearers when compared with patients with combined mucosa implant
      supported mandibular complete overdenture and mainly mucosa-supported mandibular
      complete overdenture groups. CONCLUSION: Using a combined mucosa implant
      supported mandibular complete overdenture the amount of antagonistic maxillary
      alveolar bone resorption increases when compared with the mainly mucosa-supported
      complete overdenture.

PMID- 18091174
TI  - Influence of corneal structure, corneal responsiveness, and other ocular
      parameters on tonometric measurement of intraocular pressure.
AB  - PURPOSE: To estimate the relationships between ocular parameters and
      tonometrically measured intraocular pressure (IOP), to determine the influence of
      ocular parameters on different instrument measurements of IOP, and to evaluate
      the association of ocular parameters with a parameter called hysteresis. METHODS:
      Patients presenting at a glaucoma clinic were recruited for this study. Subjects
      underwent IOP measurement with the Goldmann applanation tonometer (GAT), the
      TonoPen, and the Reichert Ocular Response Analyzer (ORA), and also measurements
      of central corneal thickness (CCT), axial length, corneal curvature, corneal
      astigmatism, central visual acuity, and refractive error. Chart information was
      reviewed to determine glaucoma treatment history. The ORA instrument provided a
      measurement called corneal hysteresis. The association between measured IOP and
      the other ocular characteristics was estimated using generalized estimating
      equations. RESULTS: Among 230 patients, IOP measurements from the TonoPen read
      lowest, and ORA read highest, and GAT measurements were closest to the mean IOP
      of the 3 instruments. In a multiple regression model adjusting for age, sex,
      race, and other ocular characteristics, a 10 microm increase in CCT was
      associated with an increase of 0.79 mm Hg measured IOP in untreated eyes
      (P<0.0001). Of the 3 tonometers, GAT was the least affected by CCT (0.66 mm Hg/10
      mum, P<0.0001). Hysteresis was significantly correlated with CCT with a modest
      correlation coefficient (r=0.20, P<0.0007). CONCLUSIONS: Among parameters related
      to measured IOP, features in addition to CCT, such as hysteresis and corneal
      curvature, may also be important. Tonometric instruments seem to be affected
      differently by various physiologic characteristics.

PMID- 18091175
TI  - Case finding of angle closure glaucoma in public health examination with scanning
      peripheral anterior chamber depth analyzer.
AB  - PURPOSE: Despite the fact that the occurrence of angle closure glaucoma (ACG) or
      acute primary angle closure (PAC) can be prevented, in many cases, nonphysicians
      fail to detect them in regular health examinations before their onset. This study
      was aimed at examining the utility of a newly developed noncontact scanning
      peripheral anterior chamber depth analyzer (SPAC) in finding eyes at risk of ACG
      and acute PAC in a public health examination by nonphysicians. METHODS: A total
      of 535 local residents 40 years old or over were enrolled. In primary screening,
      nonphysicians use SPAC to determine up to 21 consecutive circumferential
      measurements of anterior chamber depth (ACD). The subjects were classified into 4
      groups on basis of the previously established criteria: group 1: all ACD values
      above the minimum value of 72% confidence interval (CI); group 2: 1 or more ACD
      values below the minimum value of 72% or less than 4 ACD values below the minimum
      value of 95% CI; group 3: 4 or more ACD values below the minimum value of 95% CI;
      and group 4: no ACD data available. All the subjects from group 3 and those from
      group 2 or group 4 who were suspected to be at risk of ACG as diagnosed by a
      glaucoma specialist were subjected to a definitive examination. RESULTS: Fifty
      seven (10.7%) subjects were recruited to the definitive examination. The final
      diagnoses were 1 subject with primary ACG (1.8%), 23 subjects with PAC (40.4%),
      15 PAC suspect subjects (26.3%), and 18 subjects (31.6%) had eyes with open
      angle. All of them were from group 3. CONCLUSIONS: SPAC detected eyes at risk of
      ACG in a public health examination.

PMID- 18091176
TI  - Daily cost of glaucoma medications in China.
AB  - PURPOSE: To determine and compare the daily cost of various glaucoma medications
      in China. MATERIALS AND METHODS: The majority of glaucoma medications
      commercially available in China were included in this research. The total number
      of drops in 1 bottle of each medication was counted drop by drop. The mean volume
      per bottle of each medication was calculated. The cost per drop, number of days
      for both eyes usage per bottle, and daily cost was calculated. RESULTS: (1) The
      volume per drop ranged from 0.03 mL (brinzolamide 1%, travoprost 0.004%,
      bimatoprost 0.03%, and latanoprost 0.005%) to 0.05 mL (timolol 0.5%-Chengrui and
      pilocarpine 0.5% and 2%-Zhenrui). (2) The cost per bottle ranged from $0.69 (US
      dollar) (timolol 0.5%-Malaisuan Saimaluo'er) to $40.78 (latanoprost 0.005%). (3)
      The number of days for both eyes usage per bottle ranged from 52 days
      (bimatoprost 0.03%) to 11 days (pilocarpine nitrate 0.5%-Zhenrui). (4) The daily
      cost for both eyes usage from expensive to cheap were latanoprost 0.005%-$0.91,
      travoprost 0.004%-$0.77, brimonidine 0.2%-$0.61, bimatoprost 0.03%-$0.46, D
      timolol 1%-$0.36, brinzolamide 1%-$0.34, pilocarpine 2%-Zhenrui-$0.28,
      levobunolol 0.5%-$0.25, betaxolol 0.25%-$0.24, pilocarpine 0.5%-Zhenrui-$0.18,
      pilocarpine 2%-Huming-$0.16, carteolol 1%-Mikelan-$0.15, carteolol 2%-Mikelan
      $0.15, pilocarpine 1%-Huming-$0.10, timolol 0.5%-Chengrui-$0.08, timolol 0.5%
      Malaisuan Saimaluo'er-$0.03. CONCLUSIONS: The daily cost of glaucoma medications
      in China ranged much more wildly than developed countries. These data may be
      useful in selecting medications for glaucoma therapy. The ophthalmic solution of
      prostaglandins is powerful in reducing intraocular pressure. However, its high
      price should be considered when selecting glaucoma medications in China.

PMID- 18091177
TI  - Attributes of female reproductive aging and their relation to primary open-angle
      glaucoma: a prospective study.
AB  - PURPOSE: We investigated the relation between age at menopause, postmenopausal
      hormone (PMH) use, and incident primary open-angle glaucoma (POAG). METHODS: We
      followed 66,417 women in the Nurses' Health Study prospectively from 1980 to
      2002. Eligible participants were > or =40 years old, free of POAG at baseline,
      provided information on menopausal status, and reported receiving eye
      examinations during follow-up. Relevant exposure data and POAG risk factors were
      updated using biennial questionnaires. We identified 447 POAG cases during follow
      up. We used proportional hazards models to calculate multivariable rate ratios
      (MVRR) of POAG and 95% confidence intervals. RESULTS: Among postmenopausal women
      overall, entering menopause before age 45 [MVRR=0.85 (0.63 to 1.14)] or at age >
      or =54 [MVRR=0.84 (0.60 to 1.18)] was not significantly associated with POAG
      compared with entering menopause at age 50 to 54. However, in secondary analysis,
      among postmenopausal women aged > or =65 years, entering menopause at age > or
      =54 years was associated with reduced risk of POAG compared with entering
      menopause at age 50 to 54 [MVRR=0.53 (0.32 to 0.89)]. Overall, compared with
      never use of PMH, past PMH use [MVRR=0.84 (0.61 to 1.18)], and current PMH use
      [MVRR=0.89 (0.70 to 1.13)] was not significantly associated with POAG. In
      secondary analysis, compared with never use of PMH, current use of estrogen with
      progestin [MVRR=0.58 (0.36 to 0.94)] was associated with a reduced risk of POAG
      characterized by intraocular pressure >21 mm Hg before visual field loss; current
      use estrogen alone [MVRR=0.93 (0.63 to 1.35)] was not significantly associated.
      CONCLUSIONS: These data suggest a possible role for declining sex hormones in
      POAG pathogenesis.

PMID- 18091178
TI  - Efficacy and safety of a systematic switch from latanoprost to travoprost in
      patients with glaucoma.
AB  - PURPOSE: To assess the efficacy and safety of systematically switching a large
      number of hospital-based glaucoma patients from latanoprost to travoprost
      therapy. MATERIALS AND METHODS: In this prospective observational study, patients
      on latanoprost were systematically switched to travoprost without washout and
      followed-up for 12 weeks. The main outcome measures were control of intraocular
      pressure (IOP), rate of switching back, and tolerability. IOP was measured at
      baseline (while on latanoprost), and at weeks 6 and 12 after switching to
      travoprost. Adverse effects were assessed and conjunctival hyperemia was graded
      using a standardized scale. RESULTS: Ninety-three consecutive patients (mean age
      63.3 +/- 12.1 y) were enrolled. Nine patients were lost to follow-up. Four
      patients (4.3%) were switched back to latanoprost after 6 weeks due to travoprost
      intolerance. There was no significant difference between mean IOP at baseline
      [16.4 +/- 3.4 mm Hg, 95% confidence interval (CI) 15.6-17.2] and that at week 6
      (15.9 +/- 4.2 mm Hg, 95% CI 14.9-16.8) (P=0.2) and week 12 (16.4 +/- 5.7 mm Hg,
      95% CI 15.1-17.7) (P=0.99). There was no significant difference in the mean
      hyperemia score at week 12 compared with baseline (P=0.09). The majority of
      patients (86.9%) felt that both medications were comparable in terms of degree of
      comfort; 5 felt that travoprost caused more redness. CONCLUSIONS: In this study,
      when glaucoma patients were systematically switched from latanoprost to
      travoprost, the efficacy and safety of the 2 medications were found to be
      comparable. A high switch rate (95.2%) was achieved with average hyperemia scores
      being comparable.

PMID- 18091179
TI  - The effect of paclitaxel on conjunctival wound healing: a pilot study.
AB  - PURPOSE: To compare the effects of mitomycin C (MMC) and paclitaxel entrapped
      within Carbopol 980 hydrogel (CH) on conjunctival wound healing. METHODS: Twenty
      rabbits were randomized into 2 groups. In group 1, limbal-based conjunctival
      flaps were created in both eyes. In this stage, eyes were randomized for 4
      different processes. In process 1, a dry cellulose sponge soaked with 0.2 mg/mL
      of MMC was applied to the scleral surface. A cellulose sponge soaked with
      balanced saline solution was applied in the same manner in process 2. In process
      3, paclitaxel 1 mg/mL entrapped within CH was placed between the conjunctiva and
      sclera. In process 4, CH without paclitaxel was applied in the same manner. The
      conjunctiva was then sutured. All procedures were applied in the same manner in
      both eyes of animals in group 2. Eyes from group 1 were sampled at the seventh
      day, and the sampling was also carried out in group 2 on day 14. The inflammatory
      response and fibrosis were evaluated with light microscopy. RESULTS: Among 4
      different processes, lower cell counts and fibrosis scores were found in eyes
      treated with MMC and paclitaxel compared with balanced saline solution and CH
      groups (P<0.05). There was no difference between eyes treated with MMC and
      paclitaxel in terms of these histopathologic parameters (P>0.05). CONCLUSIONS:
      Paclitaxel was shown to provide MMC-like antifibrotic effects during conjunctival
      wound healing, particularly when delivered with CH and might be a promising
      alternative as an adjunctive antimetabolite in glaucoma filtration surgery.

PMID- 18091180
TI  - Predictive value of early IOP in mitomycin-C augmented trabeculectomy.
AB  - PURPOSE: To determine whether early intraocular pressure (IOP) after mitomycin-C
      (MMC) augmented trabeculectomy has any predictive value for intermediate IOP
      outcome. METHODS: Retrospective case note review. All cases of trabeculectomy
      using MMC augmentation and at least 1-year follow-up during the study period were
      included. Cases where a bleb leak occurred were excluded from the analysis. Only
      first eyes operated upon during the study period were included. Patient
      demographics and postoperative course were documented and analyzed. Early IOP
      measurements at day 1, day 7, and month 1 postoperatively were correlated to IOP
      at 1 year or final follow-up. RESULTS: One hundred nineteen trabeculectomies were
      identified. Of these 27 (22.7%) had an early bleb leak and were excluded. Further
      analysis was carried out on the remaining 92 cases. Mean age of cases was 70.8
      years. Nine cases (9.8%) were repeat trabeculectomies. Mean follow-up time was
      18.5 months (range 12 to 60 mo). Patients with a final IOP of < or =16 mm Hg
      (without drops or further surgery) (unqualified successes) had a mean day 1 IOP
      of 12.5 mm Hg compared with 17.4 mm Hg in those with an IOP more than 16 mm Hg at
      final follow-up (P=0.02). Patients with a final IOP of < or =16 mm Hg (with or
      without drops) (qualified successes) had mean day 1 IOP of 13.3 mm Hg compared
      with 17.1 mm Hg in those with an IOP of >16 mm Hg at final follow-up (P=0.06). At
      1 month the mean IOPs were 10.7 mm Hg and 19.5 mm Hg, respectively (P<0.001). By
      logistic regression analysis at final recorded visit those cases in the lowest
      IOP quartile at 1 month were 14 times more likely to have an IOP < or =16 mm Hg
      without treatment than those in the highest quartile at 1 month. CONCLUSIONS: Our
      data suggests that a low early postoperative IOP measurement is a predictive
      factor for IOP value and success after intermediate length follow-up in patients
      undergoing trabeculectomy surgery augmented with MMC.

PMID- 18091181
TI  - The efficacy of a modified ACTSEB (anterior chamber tube shunt to an encircling
      band) procedure.
AB  - PURPOSE: To evaluate the efficacy of a modified anterior chamber tube shunt to an
      encircling band (ACTSEB) procedure for treating intractable glaucoma after
      scleral buckling procedure. METHODS: A retrospective review of medical records
      was performed on 7 eyes of 5 patients who underwent a modified ACTSEB procedure
      to treat intractable glaucoma after an encircling procedure. The modified ACTSEB
      procedure was performed using a silicone tube with its distal end inserted into
      the fibrous capsule around a scleral buckle and its proximal end inserted into
      the anterior chamber. Preoperative and postoperative intraocular pressure (IOP),
      number of antiglaucoma medications, visual acuity, and complications were
      recorded. Success was defined as a final IOP of >6 mm Hg and <21 mm Hg with or
      without medication. Among them qualified success was defined as a final IOP of
      <22 mm Hg with antiglaucoma medication, and complete success as the same IOP
      without medication. RESULTS: The overall success rate was 86% (6/7). Qualified
      success rate was 71% (5/7), and the complete success rate 14% (1/7). No case of
      hypotony, shallow anterior chamber, fibrous tube occlusion, tube obstruction by
      lens or iris, conjunctival wound leak, hyphema, or epithelial ingrowth occurred.
      The only complication was of inferior migration of the silicone tube into the
      anterior chamber in 2 cases. One of these led to corneal decompensation and
      subsequent tube removal due to tube migration, and the other underwent tube
      repositioning at 14 months postoperatively. CONCLUSIONS: The modified ACTSEB
      procedure provides an efficient means of treating intractable glaucoma after
      scleral buckling procedure.

PMID- 18091182
TI  - Relationship between intraocular pressure and obesity in children.
AB  - PURPOSE: To establish the relationship between intraocular pressure (IOP) and
      obesity in children. METHODS: Seventy-two obese children (body mass index in the
      95th percentile or greater) were compared with 72 age-matched and sex-matched
      controls (body mass index <95th percentile). Both groups underwent Goldmann
      applanation tonometry (3 times), blood pressure measurement (3 times), and Hertel
      exophthalmometry. Paired and unpaired t tests and the Cochran-Mantel-Haenzel
      statistics were used for statistical analysis. RESULTS: The mean IOP between the
      obese children and controls were significantly different (P<0.0001), even after
      adjusting for systolic and diastolic blood pressure (P<0.001). Diurnal variation
      of IOP was higher in obese children (P<0.001). Obese children had higher Hertel
      values (P<0.001). Sex did not significantly effect IOP in either group (P>0.05).
      CONCLUSIONS: In addition to its indirect effect on IOP via blood pressure change,
      obesity is also an independent risk factor for increased IOP.

PMID- 18091183
TI  - Trabeculectomy with mitomycin C versus Ahmed glaucoma implant with mitomycin C
      for treatment of pediatric aphakic glaucoma.
AB  - PURPOSE: To compare trabeculectomy with mitomycin C (T+MMC) and Ahmed glaucoma
      implant with MMC (AGI+MMC) in treatment of aphakic glaucoma in children below 16
      years of age. DESIGN: Randomized clinical trial. PARTICIPANTS: Subjects less than
      16 years of age who had previously undergone anterior lensectomy and vitrectomy
      for treatment of congenital cataract with unresponsive aphakic glaucoma (at least
      on 2 medications) were allocated in 2 groups: trabeculectomy with MMC (group A,
      15 eyes) and AGI (group B, 15 eyes). METHODS: Fifteen eyes in each group
      underwent T+MMC or AGI+MMC. Complete and qualified success were defined as 5< or
      =intraocular pressure< or =21 mm Hg without and with medication, respectively.
      MAIN OUTCOME MEASURES: Intraocular pressure, visual acuity, and complications.
      RESULTS: Complete and qualified success rates were 33.3% and 40% in T+MMC group
      versus 20% and 66.7% in AGI+MMC group, respectively (P=0.36). Mean follow-up was
      14.8 and 13.1 months and complication rates were 40% and 26.7% (P=0.44),
      respectively. CONCLUSIONS: T+MMC and AGI+MMC are comparable in terms of success
      rate and complications in pediatric aphakic glaucoma. PRECIS: This randomized
      clinical trial demonstrated comparable safety and efficacy for MMC trabeculectomy
      and AGI in the treatment of pediatric aphakic glaucoma.

PMID- 18091184
TI  - Tube extender for revision of glaucoma drainage implants.
AB  - PURPOSE: Our purpose was to evaluate the clinical experience with a glaucoma
      drainage implant tube extender. METHODS: This was a noncomparative retrospective
      case series of 10 patients treated with a Tube Extender (New World Medical, Inc,
      Rancho Cucamonga, CA), with average follow-up of 23 months. RESULTS: The majority
      of patients (n=7) were treated for tube retraction, 1 had kinked tube, 1 had tube
      exposure and malposition, and 1 had inadvertently cut tube. Implant types
      included the Ahmed glaucoma valve (n=7), Molteno implant (n=2), and Baerveldt
      implant (n=1). The mean intraocular pressure and number of glaucoma medications
      were significantly reduced postoperatively (P=0.007 and 0.001, respectively).
      Intraocular pressure or glaucoma medications decreased in 9 patients, and all
      patients achieved surgical success. CONCLUSIONS: The Tube Extender is a useful
      device when the tubes of glaucoma drainage implants from different manufacturers
      require lengthening.

PMID- 18091185
TI  - Changes in scanning laser polarimetry before and after laser capsulotomy for
      posterior capsular opacification.

PMID- 18091187
TI  - The prevalence of myopia in eyes with angle closure.
AB  - Primary angle closure (PAC) typically occurs in eyes, which have a short axial
      length and a shallow anterior chamber. In myopic eyes, the axial length is
      usually longer than average and the anterior chamber is usually deep; PAC is
      rarely observed in these eyes. In a retrospective chart review of 322 cases of
      PAC, 6 cases occurred in myopic eyes. All cases were diagnosed by the use of
      indentation gonioscopy. This review emphasizes the importance of gonioscopy to
      detect PAC, even in myopic eyes.

PMID- 18091188
TI  - Early intervention for psychosis and schizophrenia.

PMID- 18091189
TI  - Hopelessness in schizophrenia: the impact of symptoms and beliefs about illness.
AB  - Risk factors for the development of hopelessness in schizophrenia remain poorly
      understood. This study investigated how psychiatric symptom levels and beliefs
      about illness might be linked to hopelessness in 100 patients with DSM-IV
      schizophrenia. Participants were assessed on the Beck Hopelessness Scale (BHS),
      the Calgary Depression Scale for Schizophrenia (CDSS), the Personal Beliefs about
      Illness Questionnaire (PBIQ), the Brief Psychiatric Rating Scale (BPRS), and the
      Scale for the Assessment of Negative Symptoms (SANS). Severe levels of
      hopelessness were found in 25% of the sample. There were significant differences
      between the hopeless and nonhopeless participants on the PBIQ subscales, SANS and
      BPRS. Differences on the PBIQ subscales remained significant when depression
      scores were controlled for. The total CDSS score, the "humiliating need to be
      marginalized" PBIQ subscale, and total BPRS score contributed significantly to a
      model accounting for 60% of the variance in hopelessness scores. Processes
      potentially implicated in the emergence of hopelessness in schizophrenia are
      discussed.

PMID- 18091190
TI  - The impact of insight on functioning in patients with schizophrenia or
      schizoaffective disorder receiving risperidone long-acting injectable.
AB  - This post hoc analysis explored the role of insight as a mediator of functioning
      in a 52-week, double-blind, international trial of 323 patients with
      schizophrenia or schizoaffective disorder receiving risperidone long-acting
      injectable. Measures included the Positive and Negative Syndrome Scale (PANSS)
      insight item, PANSS factors, Clinical Global Impressions-Severity (CGI-S),
      Strauss-Carpenter Levels of Functioning (LOF), Personal and Social Performance
      (PSP) scale, and a cognitive test battery. Correlation/regression analyses
      examined associations between demographic and clinical characteristics, including
      insight, and functional measures. Insight scores correlated significantly with
      CGI-S, PANSS subscales, PSP, LOF, and several cognitive measures. Regression
      models demonstrated that changes in insight, changes in negative symptoms, and
      study duration were significantly associated with PSP and LOF total change
      scores. Findings identified important variables to consider for intervention to
      improve functioning in schizophrenia.

PMID- 18091191
TI  - Cognitive functioning in depersonalization disorder.
AB  - Depersonalization disorder (DPD) is a dissociative disorder characterized by a
      subjective sense of unreality and detachment, and has been associated with
      deficits in perception and short-term memory. In this study, 21 DPD and 17
      healthy comparison participants free of psychiatric disorders were administered a
      comprehensive neuropsychologic battery. The groups did not differ in full-scale,
      verbal, and performance IQ (Wechsler Adult Intelligence Scale), in working memory
      (Paced Auditory Serial Addition Test), or in selective attention (Digit Span with
      Distracters). The DPD group performed significantly worse on immediate visual and
      verbal recall (Wechsler Memory Scale, Revised), but not on delayed recall.
      Dissociation severity was significantly correlated with processing slowness and
      distractibility. We conclude that DPD is associated with cognitive disruptions in
      early perceptual and attentional processes.

PMID- 18091192
TI  - Depersonalization and individualism: the effect of culture on symptom profiles in
      panic disorder.
AB  - It has been proposed that highly individualistic cultures confer vulnerability to
      depersonalization. To test this idea, we carried out a comprehensive systematic
      review of published empirical studies on panic disorder, which reported the
      frequency of depersonalization/derealization during panic attacks. It was
      predicted that the frequency of depersonalization would be higher in Western
      cultures and that a significant correlation would be found between the frequency
      of depersonalization and individualism scores of the participant countries. As
      predicted, the frequency of depersonalization during panic was significantly
      lower in nonwestern countries. There was also a significant correlation between
      frequency of depersonalization and Individualism (rho = 0.68, p < 0.0001), and
      between fears of losing control (rho = 0.57, p = 0.005) and individualism. These
      findings are interpreted in light of recent studies suggesting that
      individualistic cultures are characterized by hypersensitivity to threat and by
      an external locus of control. Two features may be relevant in the genesis of
      depersonalization.

PMID- 18091193
TI  - Beliefs, mental health, and evolutionary threat assessment systems in the brain.
AB  - This article reviews aspects of the literature on neuroscience, psychiatry, and
      cognitive and evolutionary psychology to illustrate how primitive brain
      mechanisms that evolved to assess environmental threats underlie psychiatric
      disorders, and how beliefs can affect psychiatric symptoms through these brain
      systems. Psychiatric theories are discussed that (a) link psychiatric disorders
      to threat assessment and (b) explain how the normal functioning of threat
      assessment systems can become pathological. Three brain structures that are
      consistently implicated in psychiatric symptomology also are involved in threat
      assessment and self-defense: the prefrontal cortex, the basal ganglia, and parts
      of the so-called limbic system. We propose that as these structures evolved over
      time they formed what we refer to as evolutionary threat assessment systems,
      which detect and assess potential threats of harm. Drawing on various
      psychological and psychiatric theories we propose how beliefs about the world can
      moderate psychiatric symptoms through their influence on evolutionary threat
      assessment systems.

PMID- 18091194
TI  - Screening for posttraumatic stress disorder: what combination of symptoms
      predicts best?
AB  - Several symptom screening instruments have been developed to identify trauma
      survivors at risk for chronic posttraumatic stress disorder, but few of these
      have been thoroughly evaluated to date. In this study, a range of symptom
      combination scoring rules derived from the literature were applied to the
      Posttraumatic Diagnostic Scale and evaluated in 4 different samples of trauma
      survivors (total N = 522) regarding their power to identify people with
      posttraumatic stress disorder. Results were replicated in a fifth sample (N =
      253). Most scoring rules showed lower diagnostic efficiencies than in the
      original reports. The most stable results were obtained for cutoffs on the
      Posttraumatic Diagnostic Scale total scale and a new subset of 8 items. The
      results underscore the need to cross-validate findings before using screening
      instruments for clinical applications.

PMID- 18091195
TI  - Structured group psychotherapy in adults with attention deficit hyperactivity
      disorder: results of an open multicentre study.
AB  - Attention deficit hyperactivity disorder (ADHD) is a serious mental disorder that
      often persists in adulthood. In a pilot study, a structured skills training group
      program for adult ADHD led to significant symptomatic improvements. The present
      study evaluated the program's effectiveness, feasibility, and patient
      acceptability in a multicenter setting. Seventy-two adult ADHD patients were
      assigned to 13 two-hour weekly sessions at 4 different therapy sites. The therapy
      was well tolerated and led to significant improvements of ADHD, depressive
      symptoms, and personal health status (p < 0.001). The factors treatment site and
      medication did not contribute to the overall improvement. Patients regarded the
      program topics "behavioral analyses," "mindfulness," and "emotion regulation" as
      the most helpful. In this multicenter study, the therapy program showed therapist
      independent effects and seemed to be disorder-specific. This warrants the effort
      of organizing further controlled studies.

PMID- 18091196
TI  - Racial and ethnic disparities in mental illness stigma.
AB  - The present study sought to examine whether racial/ethnic differences exist in
      stigmatizing attitudes towards people with mental illness among community college
      students. Multiple regression models were used to investigate racial/ethnic
      differences in students' perceived dangerousness and desire for segregation from
      persons with mental illness both before and after participation in an antistigma
      intervention. At baseline, African Americans and Asians perceived people with
      mental illness as more dangerous and wanted more segregation than Caucasians, and
      Latinos perceived people with mental illness as less dangerous and wanted less
      segregation than Caucasians. Similar patterns emerged postintervention, except
      that Asians' perceptions changed significantly such that they tended to perceive
      people with mental illness as least dangerous of all the racial/ethnic groups.
      These findings suggest that racial/ethnic background may help to shape mental
      illness stigma, and that targeting antistigma interventions to racial/ethnic
      background of participants may be helpful.

PMID- 18091197
TI  - Interactive effects of emotional and restrained eating on responses to chocolate
      and affect.
AB  - To examine differences and interactions between emotional and restrained-eating
      healthy adults (56 women, 53 men) were classified into emotional or restrained
      eaters, and persons scoring high or low on both dimensions. Participants tasted
      different types of chocolate (with 30, 70, 85, or 99% cocoa content) and
      completed questionnaires on affect and attitudes towards chocolate. Emotional
      eaters reported increased craving for and increased consumption of chocolate,
      whereas restrained eaters experienced chocolate-related guilt. However,
      restrained eaters rated plain chocolate (70% and 85% cocoa) as more pleasant than
      other groups. Persons scoring high on both dimensions showed heightened negative
      affect and may be prone to disturbances of eating and affect.

PMID- 18091198
TI  - Morphologic alterations in the corpus callosum in abuse-related posttraumatic
      stress disorder: a preliminary study.
AB  - Magnetic resonance imaging (MRI) studies in children with maltreatment-related
      posttraumatic stress disorder (PTSD) have demonstrated smaller corpus callosum
      area, with the greatest magnitude of change in posterior portions of the corpus
      callosum. The purpose of this study was to measure corpus callosum area in adult
      female patients with childhood abuse-related PTSD and comparison subjects. MRI
      was used to measure the midsagittal area of the corpus callosum as well as
      subregions of the corpus callosum in 9 female subjects with abuse-related PTSD
      and 9 healthy female subjects. No differences were found in total area of the
      corpus callosum or in individual subregions, but the subregion/total area ratio
      was significantly smaller in posterior midbody in PTSD compared with the healthy
      subjects. These results suggest that relatively smaller areas of the posterior
      midbody of the corpus callosum are associated with childhood abuse related PTSD
      in adults; these findings are consistent with findings in children with abuse
      related PTSD.

PMID- 18091199
TI  - Role of the pediatric intensivist in the management of pediatric trauma.
AB  - There is a substantial body of evidence supporting the importance of the
      intensivist, and the importance of active involvement of the intensivist in day
      to-day management of patients, although there are much fewer data for pediatric
      trauma. Postoperative management of the pediatric trauma patient is complex and
      includes many nonsurgical areas of expertise, such as management of respiratory
      and renal failure, nutritional support, metabolic support, prevention and
      management of infection, and sepsis. Collaborative multidisciplinary care of
      these children should include the active and officially acknowledged involvement
      of pediatric intensivists side by side with their surgical colleagues.

PMID- 18091201
TI  - Measuring the cost-effectiveness of technologic change in the treatment of
      pediatric traumatic brain injury.
AB  - Substantial variation exists with respect to the management of traumatic brain
      injuries (TBI) in children. Centers that practice aggressive treatment of TBI may
      improve survival, but it is not clear that the outcomes can be justified using
      cost-effectiveness criteria. This study illustrates the use of cost-effectiveness
      analysis to assess interventions for improving outcomes in children by assessing
      the cost per quality-adjusted life year (QALY) gained from technological change
      in the treatment of TBI. Cost and survival data associated with technological
      change in the treatment of pediatric TBI was based on nationally representative
      hospital administrative data for all children <21 years with a TBI who required
      endotracheal intubation or mechanical ventilation. With QALYs of pediatric TBI
      survivors based on life expectancies ranging between 5 and 30 years and on an
      estimated preference score of approximately 0.5, the estimated incremental cost
      effectiveness ratio ranges between $19,000 and $109,000 per QALY gained. Adding
      estimated rehabilitation costs increases the cost-effectiveness ratio to between
      $57,000 and $244,000 per QALY. Sensitivity analysis indicates that estimates of
      life years gained are critical to the estimated ratio. If TBI survivors live more
      than 5 years, then the estimated cost-effectiveness ratio seems favorable.

PMID- 18091203
TI  - Measuring children's health-related quality of life after trauma.
AB  - Consideration of children's health-related quality of life (HRQOL) after injury
      is a critical aspect of outcome in assessing the effectiveness of trauma care.
      Numerous instruments are available today for measuring the HRQOL of injured
      children. HRQOL instruments reflect the subjective perspective of the impact an
      injury or disease has on a child's physical, emotional, and social well being.
      Most studies to date have examined children's HRQOL during the first year
      postinjury, relatively little is known about children's long-term HRQOL after
      trauma. Most trauma outcome studies have included children with heterogeneous
      injuries so the impact of specific injuries on HRQOL outcomes has not been well
      established. The majority of outcome studies have focused on injured children who
      have been hospitalized, however the research should be extended to the emergency
      department because a large proportion of injured children are treated and
      released from there. In addition to documenting recovery, investigators should
      use HRQOL instruments to evaluate the quality of care we offer injured children
      and their families. Rigorously conducted HRQOL assessment will provide valuable
      information that we can use to successfully optimize children's recovery after
      trauma.

PMID- 18091205
TI  - Effect of emergency department care on outcomes in pediatric trauma: what
      approaches make a difference in quality of care?
AB  - Deriving evidence-based best practice for each phase or setting of trauma care is
      necessary to maximize best outcomes. There is a paucity of studies examining the
      association of provider training on pediatric trauma outcomes. Pivotal decisions
      (whether and where to transfer, diagnostic workup, and initial resuscitation)
      occur in this setting, yet there is little evidence relating to best practices in
      those areas. Classic process-performance measures such as time intervals during
      care (e.g., time to computerized tomography scan, time to operating room, etc.)
      or utilization measures (American College of Surgeons designation) are commonly
      used in the trauma center certification process, yet process-outcome links
      relevant to children are lacking. Although great advances have been made in the
      trauma care delivered to children, scientific proof is lacking and much more
      needs to be done to establish the evidence-based need to deliver the highest
      quality of pediatric trauma care.

PMID- 18091206
TI  - Improving outcomes in pediatric trauma care: essential characteristics of the
      trauma center.
AB  - The best outcome after pediatric injury can be anticipated when the entire trauma
      team is prepared, knowledgeable, and appreciative of the unique aspects of
      pediatric trauma and pays strict attention to all aspects of the care of the
      injured child. Five aspects should be considered essential elements in the
      delivery of care by any trauma team: preparation, equipment, and training;
      prevention of secondary insults after brain injury; the ability to recognize when
      nonoperative therapy should not be attempted or when it should be abandoned;
      consideration of the psychological impact of injury on a child; and, the role of
      trauma centers in injury prevention. Each of these areas encompasses important
      unanswered questions.

PMID- 18091207
TI  - Pediatric intensive care quality factors.
AB  - Intensive care has been in the forefront of quality investigations. Outcomes
      researchers have taken advantage of reliable and robust methods to adjust for
      severity of illness and other case mix variables, and readily identifiable
      relevant outcomes (survival and death) to investigate quality factors associated
      with improved risk-adjusted outcomes. Current studies are limited by using
      databases of convenience, use of historical controls, small sample sizes, and
      inadequate case-mix adjustment. Only one study has focused on the comparative
      advantage of pediatric versus adult intensive care units for injured children; it
      demonstrated substantially improved risk-adjusted mortality rates. The effect of
      volume on quality of pediatric intensive care has been the subject of multiple
      evaluations, although each of these studies has serious limitations. Other
      studies have demonstrated that the experience of the bedside caregiver is
      important in patient outcomes.

PMID- 18091208
TI  - Ethical considerations about observational research in children.
AB  - Observational research includes a subset of the broad range of benefits and risks
      in pediatric research. The exclusive, direct benefit of observational research is
      the generation of scientific knowledge. This benefit allows for easier
      communication with families by avoiding the misunderstanding that their child
      will directly benefit. However, pediatric research that does not offer a prospect
      of direct benefit can only have limited risks in accordance with the US
      regulations. The risks of observational research relate to any adverse effects
      from the disclosure of information from: 1) personally identifiable health
      information, 2) questionnaires and interviews about health related experiences
      and 3) data from biological samples for genetic and molecular studies. Whether
      these privacy and confidentiality risks exceed a "minor increase" over minimal
      risk, depends on the likelihood that confidentiality will be breached, the
      likelihood that the breach will result in harm, and the magnitude of the harm.
      Efforts like database encryption and linked codes can minimize these risks. These
      issues become more complicated when information has sufficient clinical value to
      warrant direct disclosure to the family. It is important to communicate basic
      information to parents about such risks when obtaining parental permission.
      Further, obtaining consent from adults who have participated in pediatric
      observational research shows respect for their participation and can facilitate
      trust. However, if such adults can not be located, when the research has
      sufficient social value, continual use of the data for ongoing analysis is
      appropriate.

PMID- 18091210
TI  - Towards improving the outcomes of injured children.

PMID- 18091212
TI  - Pediatric trauma care: defining a research agenda.

PMID- 18091213
TI  - The National Study on Costs and Outcomes of Trauma.
AB  - The National Study on the Costs and Outcomes of Trauma Care (NSCOT) was designed
      to address the need for better information on the value of trauma center care. It
      is a multi-institutional, prospective study that involved the examination of
      costs and outcomes of care received by over 5,000 adult trauma patients 18 to 84
      years of age treated at 69 hospitals located in 12 states. The study had three
      major objectives: (1) to examine variations in care provided to trauma patients
      in Level I trauma centers and nontrauma center hospitals; (2) to determine the
      extent to which differences in care correlate with patient outcome, where outcome
      is defined not just in terms of mortality and morbidity, but also in terms of
      major functional outcomes at 3 months and 12 months after injury; and (3) to
      estimate acute and 1-year treatment costs for trauma center and nontrauma center
      care, and to describe the relationship between costs and effectiveness for trauma
      centers and nontrauma centers. In this article, we describe the design of the
      NSCOT study and point to some of the methodological challenges faced in its
      implementation and in the analysis of the data. We also present a description of
      the study population to serve as a basis of future reports. We conclude with
      lessons learned and some recommendations for future research.

PMID- 18091214
TI  - Traumatic injury and children: a national assessment.
AB  - Before beginning a study of trauma care for children, it is necessary to
      understand contemporary injury patterns of children, specifically the volume and
      types of injury, injury severity, and institutions where children are
      hospitalized for trauma. This article was designed to address these issues using
      the Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID)
      2003 that contains over 7 million discharge records from hospitalized children in
      the United States. Our classification of hospitals into pediatric experience and
      trauma experience are a first step in better defining what hospital
      characteristics are important to the optimal care of an injured child. In an era
      of limited resources, we would like to assure that the right child received the
      right treatment at the right place.

PMID- 18091216
TI  - Prior studies comparing outcomes from trauma care at children's hospitals versus
      adult hospitals.
AB  - Current evidence suggests that the majority of injured children are not treated
      in a pediatric trauma center. This review failed to provide a definitive answer
      to the question of whether injured children treated at children's hospitals or
      adult hospitals with a dedicated pediatric unit have better outcomes than those
      treated at adult hospitals. However, it identified areas that have been
      addressed, and more importantly, uncovered others that are largely unanswered. In
      lieu of a prospective randomized trial, the next best way to address these
      unsolved issues would be a prospective collection of data with careful attention
      to assessing injury severity, physiologic response to the injury, associated
      injuries and comorbidities, along with resuscitation techniques, hospital
      resources, and manpower training.

PMID- 18091218
TI  - Comparing processes of pediatric trauma care at children's hospitals versus adult
      hospitals.
AB  - Comparing treatment of pediatric injury by hospital type or physician expertise
      has often created more controversy than conformity. Three key components that
      help define quality of care include infrastructure, process, and outcome. This
      report highlights studies that compared processes of care by physician and
      hospital expertise with regard to injured children. During the past 15 years,
      numerous studies have compared both hospital and physician expertise in the
      processes of pediatric trauma care. From these studies, it is clear that
      evaluation of processes of care is equally important as evaluating outcome,
      especially when mortality is the outcome variable. Future studies should examine
      other aspects of care in addition to surgical processes that might impact either
      rates of complications or long-term outcomes.

PMID- 18091219
TI  - Freehand dynamic endoscopic resection of an epidermoid tumor of the
      cerebellopontine angle: technical case report.
AB  - OBJECTIVE: In the last 10 years, experience with endoscopic transsphenoidal
      surgery for the treatment of sellar and perisellar lesions has highlighted
      advantages brought about by the endoscope for less-invasive procedures. Focusing
      on these advantages, there is increasing interest in endoscope use for treatment
      of lesions located in other regions such as the cerebellopontine angle (CPA).
      Epidermoid tumors, especially those located on the CPA, resulting from their
      avascular and noninfiltrative nature, appear particularly suited to being treated
      using an endoscopic approach. CLINICAL PRESENTATION: A 37-year-old man with a 2
      year history of left trigeminal neuralgia responded poorly to medical therapy.
      Magnetic resonance imaging scans revealed a left CPA lesion compatible with an
      epidermoid tumor, and he was admitted for surgical treatment. TECHNIQUE: We
      report a patient who underwent freehand dynamic endoscopic resection of an
      epidermoid tumor of the CPA. This technique requires two surgeons to work in
      close cooperation: the "navigator," who holds the endoscope and makes fine
      position adjustments, and the "pilot," who uses both hands to perform the
      procedure itself under dynamic endoscopic view. CONCLUSION: The patient's
      postoperative course was uneventful. The trigeminal neuralgia completely
      resolved, and postoperative control magnetic resonance imaging scans demonstrated
      no residual lesion. The benefits of endoscopic treatment for CPA lesions, with
      special emphasis on the dynamic aspect of this new technique, are discussed.

PMID- 18091220
TI  - Performance of a new type of suction tip attachment during intramedullary tumor
      dissection: technical note.
AB  - OBJECTIVE: We describe an innovative 1.7-mm-diameter, latex-free aspirator tip
      attachment (Circle Medical B.V., Wijchen, The Netherlands). This tip is designed
      to be used during tumor resection to avoid surgical trauma to the spinal cord
      surrounding an intramedullary tumor and the associated blood vessels. PATIENTS
      AND METHODS: Since 2004, we have used a this device during tumor dissection for
      36 patients with intramedullary spinal cord tumors (21 ependymomas, 7
      astrocytomas, 6 hemangioblastomas, and 2 cavernomas) and 1 patient with an
      arteriovenous malformation. The innovative feature of this attachment is the
      removable and disposable, soft, thermoplastic elastomer tip that is fenestrated
      to keep air flowing and prevent a vacuum. RESULTS: During its use, this aspirator
      tip did not adhere to tissue, including swollen spinal cord tissue that
      surrounded the tumors. We found that the tip is used more as a dissector than an
      aspirator. It must be cleaned two or three times per intervention; however, it
      was never necessary to change it. CONCLUSION: This new, safe, soft-tipped suction
      tip attachment can increase surgical safety during intramedullary tumor removal
      and its use may be extended to other neurosurgical indications such as cauda
      equina tumors and any lesion that requires nerve and vessel dissection.

PMID- 18091221
TI  - Endoarterial management of dural arteriovenous malformations with isolated sinus
      using Onyx-18: technical case report.
AB  - OBJECTIVE: Anatomic and clinical cure of dural arteriovenous malformations (DAVM)
      with isolated sinus is difficult to achieve by endovascular means without
      previous surgical exposure. We propose a new management technique using a new
      liquid embolic agent (ethylene-vinyl alcohol copolymer [Onyx-18]; ev3 Inc.,
      Plymouth, MN) via an endoarterial approach that would avoid surgical craniotomy.
      BACKGROUND: Data of three consecutive patients with a DAVM with isolated sinus
      treated at our department between January 2005 and June 2005 are described.
      Procedures performed under general anesthesia consist of an arterial approach
      whereby a microcatheter is navigated via a meningeal feeder to the DAVM. Onyx-18,
      which diffuses under aqueous conditions, is then delivered, mechanically filling
      the isolated sinus and ultimately treating it. RESULTS: The patients included two
      men and one woman aged 69, 71, and 64 years, respectively. All patients were
      classified as Merland Type IV. Two patients presented with DAVMs involving the
      transverse-sigmoid sinus, and one patient presented with a DAVM involving the
      superior sagittal sinus with an isolated venous collector. All three fistulae
      were treated with transarterial embolization, using Onyx-18, through the filling
      of the pathological sinus via the anterior meningeal artery branch of the
      ophthalmic artery (DAVM at the superior sagittal sinus), and the other two
      patients were treated by means of the petrosquamous branch of the middle
      meningeal artery (DAVM at the transverse-sigmoid sinus). Postoperative digital
      subtraction angiography confirmed the elimination of the DAVMs in all three
      patients. The follow-up study ranging from 3 to 12 months (average, 7.5 mo)
      revealed no recurrence, and all of the patients had clinical improvement and
      recovered to their full activities. CONCLUSION: DAVMs with isolated sinus and
      retrograde venous drainage to the cortical system are aggressive vascular lesions
      that can be treated by transarterial embolization using Onyx-18. This procedure
      allowed us to achieve an anatomic and clinical cure in the three patients
      consecutively treated without the need for surgical exposure of the compromised
      sinus.

PMID- 18091222
TI  - The Guglielmi detachable coil "crescent" in the endovascular treatment of
      peripheral brain aneurysms: technical case report.
AB  - OBJECTIVE: Peripheral brain aneurysms arise from the distal segments of cerebral
      arteries. They can be treated by surgery or by an endovascular approach. We
      present our experience of endovascular treatment of peripheral brain aneurysms
      with a novel endovascular device, the Guglielmi detachable coil (GDC) "crescent."
      METHODS: The GDC "crescent" is a 5-mm long, curved coil steerable beyond the tip
      of a microcatheter and detachable at a distance. The GDC "crescent" was used in
      three cases of intracranial peripheral aneurysms to occlude their parent vessel.
      RESULTS: Three peripheral brain aneurysms in three patients were successfully
      treated with parent vessel occlusion using the prototype GDC "crescent" coils,
      thereby excluding the aneurysms from the brain circulation. No complications were
      encountered. CONCLUSION: From this limited experience, the GDC "crescent" seems
      particularly suitable for the controlled endovascular occlusion of the often
      narrow parent artery of distal brain aneurysms.

PMID- 18091223
TI  - De novo aneurysm formation on middle cerebral artery branches adjacent to the
      anastomotic site of superficial temporal artery-middle cerebral artery bypass
      surgery in two patients: technical case report.
AB  - OBJECTIVE: Aneurysm formation is a complication of superficial temporal artery
      middle cerebral artery bypass surgery occurring as pseudoaneurysms caused by
      technical failure, but also as true aneurysms discovered after long-term follow
      up. CLINICAL PRESENTATION: A 53-year-old woman presented with a left internal
      carotid artery cavernous aneurysm manifesting as double vision. Superficial
      temporal artery-middle cerebral artery bypass, internal trapping of the internal
      carotid artery, and embolization were performed. Three years later, angiography
      disclosed a distal middle cerebral artery aneurysm. A 70-year-old man who had
      undergone right superficial temporal artery-middle cerebral artery bypass after
      internal carotid artery occlusion died of subarachnoid hemorrhage from a ruptured
      anterior spinal artery aneurysm 21 years later. Angiography and postmortem
      examination revealed de novo aneurysm formation on a middle cerebral artery
      branch adjoining the anastomotic site. Both patients had hypertension and
      multiplicity of aneurysms. INTERPRETATION: Both cases were de novo true aneurysms
      caused by hemodynamic stress because of saccular to fusiform shape, location
      extending to the middle cerebral artery, high perfusion pressure, projection
      along the hemodynamic stress, and presence of common risk factors. CONCLUSION:
      Bypass surgery is increasingly performed in patients with complicated aneurysms
      if sacrifice or temporary occlusion of any major vessel is required. Therefore,
      de novo aneurysm formation may not be rare in patients with risk factors such as
      hypertension or multiple aneurysms. Extended follow-up examination is required in
      such patients.

PMID- 18091224
TI  - Extended transsphenoidal approach to anterior communicating artery aneurysm:
      aneurysm incidentally identified during macroadenoma resection: technical case
      report.
AB  - OBJECTIVE: Full exposure of an aneurysm and surrounding structures with minimal
      brain retraction is important to eliminate the aneurysm safely and accurately. We
      describe an extended transsphenoidal approach for clipping an anterior
      communicating artery (ACoA) aneurysm. CLINICAL PRESENTATION: A 58-year-old woman
      had a surgical history significant for subtotal removal of a macroadenoma via the
      posterior portion of the planum sphenoidale using an extended transsphenoidal
      approach. INTERVENTION: During the tumor removal, a small unruptured ACoA
      aneurysm was incidentally found. The aneurysm was eliminated through the same
      operative route under a direct and wide view. The dural window was patched with
      abdominal fascia and sutured with 5-0 nylon in a watertight fashion. CONCLUSION:
      The extended transsphenoidal approach could expose an ACoA complex and aneurysm
      without substantial brain retraction. If the major limitations of this approach
      (e.g., postoperative cerebrospinal fluid leakage and meningitis) can be overcome
      using technical advances, this technique will offer a minimally invasive approach
      to the ACoA complex.

PMID- 18091225
TI  - Minimally invasive insertion of syringosubarachnoid shunt for posttraumatic
      syringomyelia: technical case report.
AB  - OBJECTIVE: Symptomatic posttraumatic syringomyelia affects up to 10% of patients
      with spinal cord injuries and manifests in a delayed manner as progressive
      sensorimotor changes below the level of the syrinx. Syrinx shunting, and in
      particular syringosubarachnoid shunting (SSAS), provides neurological improvement
      or stabilization in at least 50% of these patients. Given the debilitated
      condition of many of these patients, a minimally invasive approach to the
      insertion of these devices is desirable. We provide the first report of an SSAS
      inserted in a minimally invasive fashion through a tubular retractor. PATIENTS
      AND METHODS: A 27-year-old woman presented 4 years after C6 to C7 fracture
      dislocation and incomplete spinal cord injury with increasing pain and spasticity
      below the midthoracic region. Magnetic resonance imaging scan revealed a
      midthoracic syrinx that had enlarged on serial imaging. SSAS was inserted using a
      minimally invasive technique via the X-Tube retractor (Medtronic Sofamor Danek,
      Memphis, TN). Through a 2.5-cm incision, hemilaminotomy was performed, and a
      midline durotomy and myelotomy were opened for SSAS insertion under microscopic
      visualization. RESULTS: Intraoperative ultrasonography revealed successful syrinx
      decompression after SSAS insertion. The operative time was 150 minutes and
      estimated blood loss was less than 100 mL. The patient was mobilized on
      postoperative Day 1 and was discharged 38.5 hours after surgery with resolution
      of her preoperative symptoms. Postoperative magnetic resonance imaging scan
      revealed excellent decompression of the syrinx, and through 1 year of follow-up,
      the patient has had no recurrence of her syrinx-related symptoms. CONCLUSION:
      This is the first report of minimal-access insertion of an SSAS. The minimally
      invasive technique appears to be a safe and effective means of implanting an
      SSAS. This approach allows for diminished blood loss and early mobilization and
      transfer to rehabilitation units for these patients.

PMID- 18091226
TI  - Deep brain stimulation for obsessive-compulsive disorder: using functional
      magnetic resonance imaging and electrophysiological techniques: technical case
      report.
AB  - OBJECTIVE AND IMPORTANCE: To demonstrate the pattern of activation associated
      with electrical stimulation through bilateral deep brain stimulation electrodes
      placed within the anterior limb of the internal capsule to the level of the
      ventral striatum for treatment of obsessive-compulsive disorder. CLINICAL
      PRESENTATION: A 44-year-old man with a 26-year history of obsessive-compulsive
      disorder underwent functional magnetic resonance imaging (fMRI) and deep brain
      stimulation-evoked cortical potential testing after bilateral implantation of
      deep brain stimulation leads. Stimulation was delivered independently through the
      distal two contacts of each percutaneously extended lead using an external pulse
      generator. On postoperative Day 2, we used a 3-Tesla magnetic resonance system to
      measure changes in the fMRI blood oxygen level-dependent signal using stimulation
      parameters that were predetermined to demonstrate behavioral effects.
      INTERVENTION: All studies were well tolerated. Trial stimulations performed
      intraoperatively as well as on postsurgical Day 1 were associated with acutely
      elevated mood and reduced anxiety. Although the benefit achieved acutely was
      relatively symmetric between the bilaterally placed leads, follow-up programming
      showed a clear advantage to right-sided stimulation. Three of the four fMRI
      trials demonstrated good activation, with the fourth being moderately corrupted
      by motion artifact. The beneficial effects observed with right-sided stimulation
      were associated with activation of the ipsilateral head of the caudate, medial
      thalamus, and anterior cingulate cortex as well as the contralateral cerebellum.
      The distribution of the cortical evoked potentials was consistent with the locus
      of cortical activation observed with fMRI. CONCLUSION: High-frequency stimulation
      via a lead placed in the anterior limb of the internal capsule induced widespread
      hemodynamic changes at both the cortical and subcortical levels including areas
      typically associated with the pathogenesis of obsessive-compulsive disorder.

PMID- 18091227
TI  - Minimally invasive echo-guided placement of the cardiac tube in a
      ventriculoatrial shunt during pregnancy: technical note.
AB  - OBJECTIVE: We describe a minimally invasive echo-guided placement of the cardiac
      tube in a ventriculoatrial shunt in a young pregnant woman, in order to avoid any
      radiological procedure. METHODS: We used a central venous catheter placement kit
      for percutaneous echo-guided right internal jugular vein puncture located by a
      7.5 mHz microlinear probe. Through the catheter, the distal portion of the shunt
      device was positioned into the internal jugular vein to the right atrium using
      ultrasound control by a 2.5 to 3.5 mHz probe in a four-chamber transthoracic
      view. RESULTS: Sonographic guidance in percutaneous placement of a vertebral
      artery shunt is a safe and fast minimally invasive technique that improves
      success rates and decreases complications such as incidental puncture of the
      carotid artery and pneumothorax. The use of a two-dimensional echocardiographic
      apparatus in a four-chamber transthoracic view is an accurate and simple method
      to verify the position of the distal tip of the shunt in the mid-right atrium
      with no risks for the patient. CONCLUSION: The use of these two techniques allows
      a minimally invasive, safe, accurate, and complete x-ray-free procedure.

PMID- 18091231
TI  - Refinement of the extradural anterior clinoidectomy: surgical anatomy of the
      orbitotemporal periosteal fold.
AB  - OBJECTIVE: Extradural removal of the anterior clinoid process is technically
      challenging because of the limited exposure. In our study of the extradural
      anterior clinoidectomy, we describe anatomic details and landmarks to facilitate
      sectioning of the orbitotemporal periosteal fold and elevation of the temporal
      fossa dura from the superior orbital fissure. We assess the morbidity associated
      with these procedures as well as compare the indications, advantages, and
      disadvantages of intra-versus extradural clinoidectomy. METHODS: Of five formalin
      fixed cadaveric heads, four were used for cadaveric dissections and one was used
      for histological examination. RESULTS: Sectioning of the orbitotemporal
      periosteal fold revealed a cleavage plane between the temporal fossa dura and a
      thin layer of connective tissue that covers the superior orbital fissure. The
      lacrimal nerve coursed immediately medial to this surgically created cleavage
      plane. The superior orbital vein crossed laterally under the cranial nerves,
      which pass through the superior orbital fissure. This vein is particularly
      vulnerable as it is composed only of endothelium and a basal membrane.
      CONCLUSION: Both intra- and extradural techniques for anterior clinoidectomy are
      important parts of the neurosurgical armamentarium. Sharp incision of the
      orbitotemporal periosteal fold to increase the extradural exposure of the
      anterior clinoid process should be made at the level of the sphenoid ridge and
      restricted to the periosteal bridge. Subsequent blunt elevation of the temporal
      fossa dura should be performed; however, peeling of the temporal fossa dura
      should be limited to avoid cranial nerve morbidity.

PMID- 18091232
TI  - The perforator-free zone of the posterior communicating artery and its relevance
      in approaches to the interpeduncular cistern, especially the transcavernous
      approach: an anatomic study.
AB  - OBJECTIVE: Because the microsurgical working space in the interpeduncular fossa
      is very narrow, using different surgical approaches such as the pterional
      approach and/or the pretemporal transcavernous approach in combination with a
      division of the posterior communicating artery (PComm) at the longest perforator
      free zone (PFZ) can help to enlarge the microscopic field of view and the working
      space in this area of the brain. METHODS: In this microanatomic study, the
      variability of several parameters of the PComm, especially the location of the
      longest PFZ of the PComm, was examined and described in 23 cadaveric heads.
      RESULTS: In most cases, the mean length of the longest PFZ was found to be
      between 2 and 6 mm. In 80% of the cases, the longest PFZ was located closer to
      the posterior cerebral artery than to the internal carotid artery. A total of
      82.5% of all the PComms measured were of the adult type. In 55% of all arteries,
      a premamillary artery was identified. When a short and adult-type PComm obscures
      the microscopic view of the operative field, dividing the PComm is mandatory. In
      other situations, dividing the PComm is facultative. Because the PComm is usually
      predominantly irrigated by the internal carotid artery, it is of hemodynamic
      advantage that the longest PFZ is typically located closest to the posterior
      cerebral artery. CONCLUSION: On the basis of this descriptive anatomic study, we
      conclude that when it is needed, division of an adult-type PComm at the longest
      PFZ is usually feasible and results in a low risk of compromising the blood flow
      to the branching perforators of the PComm.

PMID- 18091233
TI  - Anatomy of the mastoid emissary vein and venous system of the posterior neck
      region: neurosurgical implications.
AB  - OBJECTIVE: The superficial venous system of the posterior neck (suboccipital
      venous plexus) is a potential source of complications from bleeding and air
      embolism. Because there is little information available about this in the
      literature, an anatomic study of the superficial posterior neck venous system and
      a morphometric analysis of the mastoid emissary vein (MEV) complex were
      undertaken. Both surgical and endovascular implications were considered. METHODS:
      The posterior craniocervical regions of 15 silicon-injected human cadaveric
      specimens were dissected. The patterns and variances of venous anatomy were
      observed. Distances between fixed bony landmarks were measured with a caliper.
      RESULTS: The suboccipital venous plexus, which forms a complex venous network
      located between the posterior muscular layers of the neck, drains to the anterior
      vertebral vein and deep cervical vein. The MEV connects this plexus to the
      sigmoid sinus. Its average diameter was 2.15 mm, and it was located a mean of
      21.14 mm from the asterion and a mean of 33.65 mm from the mastoid tip. However,
      the size of the MEV complex varied considerably. CONCLUSION: The suboccipital
      venous plexus in the posterior neck region may be very large. The size of the
      veins in the plexus varies, but the drainage pattern remains consistent. The
      plexus is a potential source of intense bleeding and air embolism during
      posterior fossa approaches. The risks are greatest for lateral surgical
      approaches, as a result of the anatomic position of the venous system. The
      described measurements can be used to approach the MEV in endovascular procedures
      that involve the sigmoid sinus.

PMID- 18091234
TI  - Evolution of surgical approaches in the treatment of petroclival meningiomas: a
      retrospective review.
AB  - OBJECTIVE: We examined the surgical approaches used at a single institution to
      treat petroclival meningioma and evaluated changes in method utilization over
      time. METHODS: Craniotomies performed to treat petroclival meningioma between
      September of 1994 and July of 2005 were examined retrospectively. We reviewed 46
      patients (mean follow-up, 3.6 yr). Techniques included combined petrosal or
      transcochlear approaches (15% of patients), retrosigmoid craniotomies with or
      without some degree of petrosectomy (59% of patients), orbitozygomatic
      craniotomies (7% of patients), and combined orbitozygomatic-retrosigmoid
      approaches (19% of patients). In 18 patients, the tumor extended
      supratentorially. Overall, the rate of gross total resection was 43%. Seven
      patients demonstrated progression over a mean of 5.9 years. No patients died. At
      36 months, the progression-free survival rate for patients treated without
      petrosal approaches was 96%. Of 14 patients treated with stereotactic
      radiosurgery, none developed progression. CONCLUSION: Over the study period, a
      diminishing proportion of patients with petroclival meningioma were treated using
      petrosal approaches. Utilization of the orbitozygomatic and retrosigmoid
      approaches alone or in combination provided a viable alternative to petrosal
      approaches for treatment of petroclival meningioma. Regardless of approach,
      progression-free survival rates were excellent over short-term follow-up period.

PMID- 18091235
TI  - Neuronavigation using an image-guided endoscopic transnasal-sphenoethmoidal
      approach to clival chordomas.
AB  - OBJECTIVE: Surgical approaches described for resection of clival tumors have been
      complicated, extensive, traumatic, and invasive. They are also associated with
      significant mortality and morbidity rates. We describe a minimally invasive,
      endoscopic transsphenoidal surgical treatment for clival tumors. METHODS: Three
      men, aged 43, 46, and 66 years, each presented with a history of headaches,
      diplopia, and multiple cranial nerve deficits. All preoperative magnetic
      resonance imaging scans showed large clival tumors. A neuronavigational image
      guided endoscopic transnasal-sphenoethmoidal approach was performed to resect the
      clival tumors. RESULTS: All three patients had near-total removal of clival
      tumors using this method, and the histology revealed chordomas. They underwent
      postoperative adjuvant radiotherapy. No complications were encountered. All
      patients were able to resume their usual activities on the same day after
      surgery. Furthermore, this technique greatly reduced patient discomfort, hastened
      recovery, and shortened the hospital stay. CONCLUSION: The neuronavigation image
      guided transsphenoidal approach is a viable, minimally invasive alternative for
      surgical treatment of clival tumors.

PMID- 18091236
TI  - Extended endoscopic transsphenoidal approach for extrasellar craniopharyngiomas.
AB  - OBJECTIVE: Suprasellar craniopharyngiomas have been classically removed using a
      variety of transcranial approaches. Historically, the transsphenoidal route was
      reserved for intrasellar-infradiaphragmatic, and preferably cystic, lesions. With
      the advent of the endoscope in transsphenoidal surgery, its obvious advantages
      combined with neurosurgeons' increasing interest in extended transsphenoidal
      approaches made suprasellar and even intraventricular craniopharyngiomas
      accessible for removal via such a low route. PATIENTS AND METHODS: Between
      January of 2004 and April of 2006, six men and four women (mean age, 57.2 yr;
      range, 26-70 yr) underwent surgery for craniopharyngioma, including two
      intrasuprasellar, one suprasellar, six suprasellar-intraventricular, and one that
      was purely intraventricular. Three patients had undergone a previous transcranial
      surgery via the pterional approach, whereas one patient had undergone a
      transsphenoidal microsurgical approach. The surgical method consisted of an
      extended endoscopic transsphenoidal approach with removal of the upper half of
      the sella, the tuberculum sellae, and the posterior part of the planum
      sphenoidale, using a "three-four hands" technique. RESULTS: Total
      craniopharyngioma removal was achieved for seven patients, subtotal removal was
      possible for two patients, and one patient had a partial removal. Two patients
      developed a postoperative cerebrospinal fluid leak that required a successful
      endoscopic revision of the cranial base reconstruction. One patient died 5 weeks
      later because of hypothalamic dysfunction. All patients with visual field and/or
      visual acuity defect improved except one patient, in which we observed a slight
      worsening of visual acuity in one eye. Preoperative pituitary dysfunction did not
      improve in any patient. In three patients, we observed the new occurrence of
      permanent diabetes insipidus. One patient developed a sphenoid sinus mycosis,
      which was treated with antimycotic therapy. We did not observe carotid injury,
      epistaxis from the sphenopalatine artery, or airway difficulties. CONCLUSION: For
      selected patients, the extended endoscopic endonasal approach for removal of
      suprasellar craniopharyngioma seems to provide a valid alternative to
      transcranial approaches.

PMID- 18091237
TI  - Extended endoscopic transsphenoidal approach for tuberculum sellae meningiomas.
AB  - OBJECTIVE: Tuberculum sellae meningiomas are classically removed through several
      different surgical transcranial approaches, including the pterional transsylvian
      route. Recently, the indications for the transsphenoidal technique, traditionally
      proposed only for the treatment of intrasellar lesions, have been extended to
      include lesions located in the supra- and parasellar areas and, among them,
      tuberculum sellae meningiomas. We describe the surgical technique for the purely
      endoscopic endonasal variant of the extended transsphenoidal "low route" to
      tuberculum sellae meningiomas. PATIENTS AND METHODS: Over a 22-month period, six
      patients (three men and three women; mean age, 56.1 yr; age range, 44-70 yr)
      underwent an extended endoscopic transsphenoidal approach for the treatment of
      tuberculum sellae meningiomas. Two lesions were less than 2 cm and four were
      between 2 and 4 cm in size. The details of the surgical technique have been
      described. RESULTS: Gross total removal of the lesion, without the need for brain
      retraction and with minimal neurovascular manipulation, was achieved in five
      patients (83.3%), whereas in one patient, only subtotal removal was possible
      (>90%) because the mass extended into the right optic canal. Four patients with
      preoperative visual function defects had complete recovery, whereas two patients
      experienced a temporary worsening of vision. Both of these patients fully
      recovered within a few days. One patient had a postoperative cerebrospinal fluid
      leak that required three operations for cranial base defect repair. This patient
      showed rapid and unexpected worsening with respect to level of consciousness and
      anisocoria. An intraventricular hemorrhage was discovered, and the patient died 6
      days later. Another patient developed new permanent diabetes insipidus that
      required hormonal replacement therapy. CONCLUSION: In experienced hands and in
      carefully selected patients, the extended endoscopic transsphenoidal approach may
      constitute a viable alternative to transcranial approaches for tuberculum sellae
      meningioma. At present, the major limits of the approach include the lack of a
      reliable technique for the reconstruction of a cranial base defect and inadequate
      follow-up.

PMID- 18091238
TI  - Double origin of the posteroinferior cerebellar artery: angiographic anatomy and
      endovascular treatment of concurrent vertebrobasilar dissection.
AB  - OBJECTIVE: The aim of this study was to evaluate the anatomic details and
      therapeutic implications of the double origin of the posteroinferior cerebellar
      artery (DOPICA). METHODS: A total of 131 patients with intracranial posterior
      circulation aneurysms were consecutively treated using endovascular techniques
      during an 8-year period. We retrospectively searched the angiographies of these
      patients for evidence of DOPICA and evaluated its anatomic and treatment details
      and outcomes in cases of concurrent vertebral artery dissection. RESULTS: DOPICA
      was found in eight patients. Five patients had a ruptured dissecting lesion at
      one posteroinferior cerebellar artery (PICA) channel and/or the vertebral artery
      of cranial PICA origin. In the remaining three patients, DOPICA was incidentally
      found in cases of P2 or basilar aneurysm. The cranial channel arose from the V4
      segment in all eight patients, whereas the caudal channel arose at the
      atlantooccipital level in seven patients and at the C1 to C2 level in one
      patient. Internal trapping was chosen to treat the dissecting lesions, because
      the remaining channel was expected to serve as a route for the PICA-territorial
      supply. Four of the five patients fully recovered, and one comatose patient
      eventually died. CONCLUSION: The cranial and caudal channels of DOPICA mainly
      arise at the levels of the intracranial and atlantooccipital spaces,
      respectively. Treatment for a ruptured dissection involving the PICA or a
      vertebral artery of PICA origin is challenging because of the fear of PICA
      territorial infarction. In such a case, the presence of DOPICA allows internal
      trapping of a dissecting lesion with reduced risk, because the other channel
      functions as an alternative flow-maintaining route.

PMID- 18091239
TI  - Stent reconstruction of wide-necked aneurysms across the circle of Willis.
AB  - OBJECTIVE: To describe a novel technique for single stent reconstruction of wide
      necked aneurysms arising from the circle of Willis. METHODS: Neuroform stents
      (Boston Scientific/Target, Fremont, CA) were placed across the basilar apex
      (right P1 to left P1) via the posterior communicating artery in two patients,
      across the left carotid terminus (left A1 to left M1) via the anterior
      communicating artery in two patients, and across the anterior communicating
      artery (left A1 to right A1) in one patient for stent-supported coil
      embolization. RESULTS: Five women underwent successful deployment of the
      Neuroform stent across the circle of Willis to support subsequent coil
      embolization of a wide-necked cerebral aneurysm. In two patients with
      subarachnoid hemorrhage, initial dome coiling was performed for short-term
      protection, and stents were applied across the circle of Willis to support
      completion of coil embolization during a second session. None of the patients
      experienced any periprocedural or delayed neurological complications. CONCLUSION:
      Stenting across the circle of Willis represents a novel adjuvant technique to
      support the coiling of selected wide-necked intracranial aneurysms. This
      technique is particularly useful for wide-necked terminal aneurysms that
      incorporate both branches of a bifurcation in a configuration unfavorable for Y
      stent reconstruction.

PMID- 18091240
TI  - The minipterional craniotomy: technical description and anatomic assessment.
AB  - OBJECTIVE: To describe a modification of the pterional approach (PT), the
      minipterional craniotomy (MPT), and compare the anatomic exposure provided by
      these two approaches. METHODS: The anatomic exposure offered by the MPT and PT
      were compared in eight sides of cadaver heads using a computerized tracking
      system, a robotic microscope, and an image-guidance system. The area of surgical
      exposure, angular exposure, and anatomic limits of each craniotomy were
      evaluated. Three recently operated clinical cases (EGF) are also reported.
      RESULTS: There were no statistical differences in the total area of surgical
      exposure between the two craniotomies (PT, 1524.7 +/- 305 mm; MPT, 1469.7 +/-
      380.3 mm; P > 0.05) or among the ipsilateral, middle, and contralateral
      components of the area (P > 0.05). There were no differences in angular exposure
      along the longitudinal and transverse axis angles for the three selected targets,
      the bifurcations of internal carotid and middle cerebral arteries, and the
      anterior communicating artery (P > 0.05). Except for the distal portion of the
      operculoinsular compartment of the sylvian fissure, no significant differences in
      the limits of the surgical exposure through the PT and MPT were apparent on the
      image-guidance system. CONCLUSION: The MPT craniotomy provides comparable
      surgical exposure to that offered by the PT. The advantages of the MPT include
      reduction of tissue trauma and bony removal, a decrease in surgical time, and
      improved cosmetic outcomes.

PMID- 18091241
TI  - Image-guided surgery for treatment of unruptured middle cerebral artery
      aneurysms.
AB  - OBJECTIVE: Direct surgical clipping appears to be an efficient means for managing
      unruptured middle cerebral artery (MCA) aneurysms, owing to several angioanatomic
      features. Here, we present a minimally invasive technique that uses navigation
      guidance for the treatment of unruptured MCA aneurysms. METHODS: Between July of
      2003 and June of 2005, we used image-guidance navigation to operate on 24
      patients who were diagnosed with unruptured MCA aneurysm. Five men and 19 women
      were included in the study, and their ages ranged from 43 to 70 years (mean, 58
      yr). We predetermined the transsylvian trajectory toward the aneurysm and planned
      a tailored craniotomy for each patient. RESULTS: All aneurysms were readily
      identified and successfully clipped via craniotomies of less than 3 cm in
      diameter. We experienced no surgical complications, and each patient had an
      uneventful postoperative course. CONCLUSION: With the aid of navigation, we were
      able to easily locate MCA aneurysms and perform minimally invasive surgeries such
      as mini-craniotomies, tailored sylvian dissections, and successful clippings of
      unruptured MCA aneurysms. In addition, we obtained satisfactory cosmetic results.

PMID- 18091242
TI  - Microsurgical management of anterior communicating artery aneurysms.
AB  - OBJECTIVE: Aneurysms of the anterior communicating (ACOM) artery are the most
      frequently occurring type of ruptured intracranial aneurysms. The peculiar
      anatomy of the anterior communicating artery complex, its anatomic variations,
      and its multiple perforators, along with the deep location of these aneurysms and
      our difficulty accessing them, pose challenging anatomic problems in their
      surgical treatment. METHODS: We present our operative techniques for
      microsurgical treatment of ACOM artery aneurysms. Special, complex situations
      that may arise during treatment of these aneurysms and their solutions are also
      discussed. We highlight the technical aspects of microsurgical clipping of ACOM
      artery aneurysms. RESULTS: Operative videos are provided to illustrate the
      technical variations of approaching and clipping these aneurysms, the A3-A3
      bypass technique, and the complexity of managing these aneurysms. CONCLUSION:
      Attention to detail is critical for successful treatment of ACOM artery
      aneurysms. Management of each patient must be tailored, because no one technique
      is suitable for all situations. Not all ACOM artery aneurysms can be coiled;
      therefore, the surgeon's microsurgical clipping technique is an important facet
      of managing these aneurysms.

PMID- 18091243
TI  - Anatomy of the nuchal ligament and its surgical applications.
AB  - OBJECTIVE: Although considered a basic maneuver for neurosurgical procedures,
      dissection of the musculature of the posterior cervical spine can be a source of
      complications during surgery. These complications include excessive blood loss, a
      loss of the plane of dissection, and injury to important structures such as the
      vertebral artery and nerve roots. Inappropriate closing of the muscular plane
      might also contribute to leakage of spinal fluid and postoperative deformation of
      the cervical spine. We review the anatomy of the nuchal ligament and describe a
      technical nuance based on the characteristics of the ligament's components, which
      can be used to assure the midline for a bloodless and atraumatic dissection.
      METHODS: We set out to determine whether or not the nuchal ligament could be used
      as a natural plane of dissection for splitting the posterior cervical
      musculature. We studied the anatomy of the nuchal ligament in five cadavers.
      RESULTS: The nuchal ligament extends from the external occipital protuberance to
      the spinous process of the seventh cervical vertebra (C7). It is covered by
      layers of cervical fascia and the aponeurosis of the trapezius muscle. It is
      composed of two portions: 1) the lamellar portion, an anterior double-layered
      portion with fatty areolar tissue interposed between its layers that inserts into
      the medial side of the bifid spinous process of the cervical vertebra; and 2) the
      funicular portion, a posterior fibrous portion that corresponds to the fusion of
      the layers of the lamellar portion. CONCLUSION: Several steps can assure that the
      midline plane is respected, thereby decreasing risk and reducing trauma and blood
      loss during dissection: 1) dissection of the nuchal ligament within the fatty
      areolar tissue of the lamellar portion, 2) isolation and incision of the
      funicular portion from inside to outside, and 3) retrograde dissection of the
      cerviconuchal muscles attached to the occipital bone in a subperiosteal plane.

PMID- 18091244
TI  - Resorbable anterior cervical plates for single-level degenerative disc disease.
AB  - OBJECTIVE: Resorbable spinal implants have generated increasing interest. There
      are minimal data in the literature on the use of resorbable anterior cervical
      plates. The purpose of this study is twofold. First, we present clinical outcomes
      of anterior cervical decompression and fusion (ACDF) for single-level
      degenerative disease using the first commercially available resorbable cervical
      plate. Second, we compare x-ray outcomes, including pseudarthrosis rates and
      angulation of healing, between patients receiving resorbable plates and a control
      group of patients receiving titanium plates. METHODS: Twenty-four consecutive
      patients treated with single-level ACDF using a resorbable anterior cervical
      plate were prospectively evaluated with minimum 12-month follow-up (mean, 15 mo).
      As a control group, 93 consecutive patients treated with single-level ACDF using
      a titanium plate with minimum 1-year follow-up were assessed. RESULTS: Overall
      outcomes were good in the resorbable plate group at a mean 15 months follow-up.
      Neck Disability Index scores decreased from a mean of 64.0 to 20.1% at follow-up
      (P < 0.001). Numerical Rating Scale pain scores decreased from a mean of 8.0
      preoperatively to 2.9 at follow-up (P < 0.001). Three cases of pseudarthrosis
      [three of 24 (12.5%)] were identified in the resorbable plate group compared with
      two cases in the control group [two of 93 (2.2%)]. This difference was
      significant (P = 0.047). Angulation was measured on final x-rays using Cobb
      angles. Patients in the resorbable plate group healed with a mean 4.52-degree
      kyphosis, whereas patients in the titanium plate group healed with a mean 2.41
      degree lordosis (P < 0.001). CONCLUSION: This report describes, to our knowledge,
      the first series of patients to undergo ACDF with the first commercially
      available resorbable cervical plate. Healing in kyphosis and pseudarthrosis was
      significantly more likely with resorbable implants as compared with the use of
      titanium plating. Although ultimate clinical outcomes were good, x-ray outcomes
      may be better with the use of titanium plating.

PMID- 18091245
TI  - Cervical crossing laminar screws: early clinical results and complications.
AB  - OBJECTIVE: C2 crossing laminar screws are a new technique for axis fixation with
      a purported lower risk for neurological or vascular injury. However, to date, few
      clinical series on this technique have appeared in the peer-reviewed literature.
      This report describes our initial clinical experience and complications using
      this new spinal fixation technique. METHODS: Thirty patients underwent high
      cervical intralaminar fixation with crossing intralaminar screws. Indications for
      surgery included occiput to cervical fixation for basilar invagination in six
      patients, fixation for atlantoaxial subluxation or trauma in six patients,
      cervical swan neck deformity in four patients, and laminectomy and instrumented
      fusion for cervical stenosis in 14 patients. Two cases involved C3 fixation
      resulting from congenital anomalies. A total of 59 screws were placed, and the
      patients were assessed both clinically and radiographically with postoperative
      computed tomographic scans. RESULTS: There were no intraoperative complications
      and no cases of neurological worsening or vascular injury from hardware
      placement. One patient reported local neck pain resulting from hardware
      prominence. Computed tomographic scans demonstrated a partial dorsal laminar
      breach in 11 patients and violation of the spinal canal in one patient. None of
      these resulted in neurological symptoms. Early hardware fractures were observed
      in two patients. CONCLUSION: Crossing C2 laminar screws provide the surgeon with
      an expanded armamentarium for fixation in the high cervical spine. This technique
      is straightforward and easily adopted. However, the unique position of the screw
      heads may result in increased stress and strain on the intralaminar screws. Thus,
      larger diameter screws or additional fixation points at adjacent levels are
      recommended.

PMID- 18091246
TI  - Thoracoscopic vertebral body replacement with an expandable cage after ventral
      spinal canal decompression.
AB  - OBJECTIVE: Minimally invasive thoracic anterior surgery using a thoracoscopic
      approach has evolved to include spinal biopsy, debridement, discectomy,
      decompressive corpectomy, interbody fusions, and internal fixations. Minimal
      access techniques can potentially decrease surgical access morbidity and also
      reduce the time required for recovery and healing. The thoracoscopic approach for
      decompression, stabilization, and anterior vertebral reconstruction of
      thoracolumbar fractures is described. METHODS: In this article and video, we
      discuss patient selection, surgical positioning, port placement, thoracic level
      localization, exposure and removal of fractured vertebral bodies, anterior
      vertebral column reconstruction using an expandable cage, instrumentation, and
      postoperative management. RESULTS: The potential advantages of using a minimally
      invasive thoracoscopic approach include direct trajectory to anterior spine
      pathology, minimal tissue and rib retraction, and decreased postoperative pain
      and length of hospital stay. The associated disadvantages include the steep
      learning curve for the surgeon, the need to operate with two-dimensional visual
      information and long instruments, and the requirement that one have an
      experienced surgical assistant. CONCLUSION: Minimally invasive surgery using a
      thoracoscopic approach for vertebral body replacement with an expandable cage can
      be performed safely. Expandable cages facilitate the vertebral body
      reconstruction via minimal access surgery.

PMID- 18091247
TI  - Stiffness of occipital-cervical constructs: beam theory.
AB  - OBJECTIVE: The purpose of this study is to show that stiffness of an occipital
      cervical construct can be predicted based on rod geometry and material. MATERIALS
      AND METHODS: Various rod-plate implants were tested as previously reported
      biomechanical studies of occipital-cervical fixation with the exception that no
      spine was used. A testing frame that holds paired contoured rods and plates to
      the same position as in the biomechanical testing protocol for occipital-cervical
      fixation was tested in the flexion-extension direction on a servo-hydraulic
      testing machine. Stiffness was determined from the plots of applied moment versus
      angular displacement. The occipital-cervical constructs were then modeled as a
      curved beam in pure bending in the sagittal plane to calculate the moment of
      inertia and theoretical stiffness. The Pearson correlation coefficient was used
      to assess the correlation of the experimental to the theoretical calculated
      stiffness. Product of inertia and material stiffness were determined for implants
      from previously published studies and the predicted rank order of this product
      was compared with the rank order of the observed biomechanical results in each
      study. RESULTS: A strong correlation was observed between the experimental and
      theoretical stiffness (R = 0.85). A strong influence of the inertia was also
      found on the experimental construct stiffness (R = 0.77). In five of six
      previously published studies, the best experimental performance was predicted
      using simple mechanical calculations. CONCLUSION: This study shows that both the
      theoretical stiffness and the calculated area moment of inertia are strongly
      correlated with the experimental stiffness of tested occipital-cervical fixation
      constructs.

PMID- 18091248
TI  - Triceps motor nerve branches as a donor or receiver in nerve transfers.
AB  - OBJECTIVE: The pattern of triceps innervation is complex and, as yet, has not
      been fully elucidated. The purposes of this study were 1) to clarify the anatomy
      of the triceps motor branches, and 2) to evaluate their possible uses as a donor
      or receiver for nerve transfer. METHODS: The radial nerve and its motor and
      cutaneous branches were bilaterally dissected from the axilla and posterior arm
      regions of 10 embalmed cadavers. RESULTS: A single branch innervates the triceps
      long head, whereas double innervation was identified for the lateral and medial
      heads. The upper branch to the lateral head originated from the radial nerve,
      whereas the lower branch to the lateral head stemmed from the lower medial head
      motor branch, which ultimately innervated the anconeus muscle. Both the long head
      and the upper medial head motor branches originated in the axillary region in the
      vicinity of the latissimus dorsi tendon. CONCLUSION: Each of the triceps' motor
      branches might be used as a donor for transfer. The triceps long head motor
      branch should be used preferentially when the intention is to establish triceps
      reinnervation.

PMID- 18091249
TI  - Coregistration of digital photography of the human cortex and cranial magnetic
      resonance imaging for visualization of subdural electrodes in epilepsy surgery.
AB  - OBJECTIVE: To develop a method for the coregistration of digital photographs of
      the human cortex with head magnetic resonance imaging (MRI) scans for invasive
      diagnostics and resective neocortical epilepsy surgery. METHODS: Six chronically
      epileptic patients (two women, four men; mean age, 34 yr; age range, 20-43 yr)
      underwent preoperative three-dimensional (3D) T1-weighted MRI scans. Digital
      photographs of the exposed cortex were taken during implantation of subdural grid
      electrodes. Rendering software (Analyze 3.1; Biomedical Imaging Resource, Mayo
      Foundation, Rochester, MN) was used to create an MRI-based 3D model of the brain
      surface. Digital photographs were manually coregistered with the brain surface
      MRI model using the registration tool in the Analyze software. By matching the
      digital photograph and the brain surface model, the position of the subdural
      electrodes was integrated into the coordinate system of the preoperatively
      acquired 3D MRI dataset. RESULTS: In all patients, the position of the labeled
      electrode contacts in relation to the cortical anatomy could be visualized on the
      3D models of the cortical surface. At the time of resection, the resulting image
      of the coregistration process provides a realistic view of the cortex and the
      position of the subdural electrode. CONCLUSION: The coregistration of digital
      photographs of the brain cortex with the results of 3D MRI data sets is possible.
      This allows for identification of anatomic details underlying the subdural grid
      electrodes and enhances the orientation of the surgeon.

PMID- 18091250
TI  - Single electrode and multiple electrode guided electrical stimulation of the
      subthalamic nucleus in advanced Parkinson's disease.
AB  - OBJECTIVE: It is still debated to what extent intraoperative electrophysiological
      techniques contribute to the outcome of subthalamic nucleus (STN) deep brain
      stimulation (DBS). Intraoperative electrophysiological recordings for
      identification of the STN can be made with one electrode or with multiple,
      simultaneously implanted electrodes. The latter provide more detailed information
      about the electrophysiological boundaries of the STN; however, implantation of
      several electrodes at one time might increase the risk of bleeding. Here we
      report the results of a study of patients with advanced Parkinson's disease, in
      which one group of patients underwent bilateral STN DBS with electrophysiological
      recordings from a single electrode, and the other group received STN DBS with
      multiple (five or fewer) simultaneously implanted electrodes. PATIENTS AND
      METHODS: Fifty-five patients suffering from advanced Parkinson's disease who
      underwent bilateral STN stimulation were included in this study. Thirty-two
      patients underwent STN DBS guided by a single semi-microelectrode, and 23
      patients underwent STN DBS guided with simultaneously implanted multiple
      microelectrodes. All patients were examined preoperatively and 3 and 12 months
      postoperatively with regard to activities of daily living, motor functions, and
      neuropsychological functions. RESULTS: We found that the simultaneous
      implantation of multiple electrodes does not increase the risk of bleeding or any
      other major intracranial complication. The use of multiple electrodes resulted in
      better motor results when compared with patients who underwent STN DBS guided
      with a single recording electrode. There were significantly more improvements in
      patients' tremor and rigidity, and as a consequence, a better total Unified
      Parkinson Disease Rating Scale, Part III score was identified during the
      medication-off phase. Despite better motor effects, patients treated with
      multiple electrodes showed subtle deterioration in neuropsychological functions,
      particularly in memory function. CONCLUSION: STN DBS performed with multiple
      electrophysiological recording electrodes resulted in better motor outcome but
      induced specific mild declines in neuropsychological functions.

PMID- 18091251
TI  - Magnetic resonance imaging-directed method for functional neurosurgery using
      implantable guide tubes.
AB  - OBJECTIVE: We present a magnetic resonance imaging-directed stereotactic system
      using implantable guide tubes for targeting deep brain nuclei in functional
      neurosurgery. METHODS: Our method relies on visualization of the deep brain
      nuclei on high-resolution magnetic resonance images that delineate the target
      boundaries and enable direct targeting of specific regions of the nucleus. The
      delivery system comprises a modified stereoguide capable of delivering an
      implantable guide tube to the vicinity of the desired target. The guide tube (in
      house investigational device) has a hub at its proximal end that is fixed within
      a burr hole and accommodates a radioopaque stylette that is inserted such that
      its distal end is at the desired target. After perioperative radiological
      confirmation of the stylette's relationship to the desired brain target, it is
      withdrawn from the guide tube, which may then act as a port for the implantation
      of an electrode for deep brain stimulation (DBS) or radiofrequency lesioning.
      Alternatively, the guide tube can be used to insert a catheter for drug delivery,
      cell transplantation, or viral-vector delivery. Implantation and verification are
      guided by magnetic resonance imaging or computed tomography, which enable the
      entire procedure to be performed under general anesthesia. The technique of
      implantation helps ensure optimal accuracy, and we have successfully used this
      device for implanting electrodes for DBS in the treatment of Parkinson's disease,
      essential tremor, and dystonia, and for implanting catheters for continuous
      delivery of glial-derived neurotrophic factor in the treatment of Parkinson's
      disease. The device also aids in securely fixing the DBS electrode or catheter to
      the cranium with ease, limiting hardware problems. RESULTS: A total of 205 guide
      tubes have been implanted in 101 patients. Major complications in these cases
      were limited to 4% of patients. At the initial implantations, 96.3% of the guide
      tubes were within 1.5 mm of the target. Ten guide tubes required reimplantation
      secondary to target errors. With corrections, the DBS electrode was delivered to
      within 1.5 mm from the planned target in all cases. CONCLUSION: This system
      provides a safe and accurate magnetic resonance imaging-directed system for
      targeting deep brain nuclei in functional neurosurgery under general anesthesia
      and avoids the need for electrophysiological monitoring.

PMID- 18091252
TI  - Total intravenous anesthesia: advantages for intracranial surgery.
AB  - OBJECTIVE: Although volatile anesthetics have been widely accepted in anesthetic
      management for neurosurgery, they reduce vascular resistance, resulting in
      increased cerebral blood flow and increased intracranial pressure (ICP). In
      patients with elevated ICP who undergo craniotomy, the increase in ICP during
      surgery from inhaled anesthetics can make the surgery more difficult, thereby
      increasing the risk of ischemic cerebral insults. Total intravenous anesthesia
      (TIVA) using propofol and analgesic drugs (remifentanil or fentanyl) and
      excluding simultaneous administration of any inhaled drugs is being used in
      patients undergoing craniotomy because of its potential to reduce ICP and ease
      access to the operative site. METHODS: We reviewed the literature and describe
      our experience with TIVA, with emphasis on hemodynamic stability, effects on ICP,
      emergence from anesthesia, extubation times, and return of cognitive function in
      patients undergoing craniotomy for space-occupying lesions. RESULTS: TIVA with
      propofol is similar to inhaled anesthetics with regard to hemodynamic stability,
      emergence times, extubation times, early cognitive function, and adverse events.
      In several prospective, randomized clinical trials, evidence suggests that ICP is
      decreased and cerebral perfusion pressure is increased in patients receiving TIVA
      when compared with those receiving volatile anesthetics during elective
      craniotomy procedures. CONCLUSION: The impact of TIVA on ICP, brain swelling, and
      access to the operative site in patients with severely elevated ICP has yet to be
      evaluated and is the subject of a future study at our institution.

PMID- 18091253
TI  - A collaborative virtual reality environment for neurosurgical planning and
      training.
AB  - OBJECTIVE: We have developed a highly interactive virtual environment that
      enables collaborative examination of stereoscopic three-dimensional (3-D) medical
      imaging data for planning, discussing, or teaching neurosurgical approaches and
      strategies. MATERIALS AND METHODS: The system consists of an interactive console
      with which the user manipulates 3-D data using hand-held and tracked devices
      within a 3-D virtual workspace and a stereoscopic projection system. The
      projection system displays the 3-D data on a large screen while the user is
      working with it. This setup allows users to interact intuitively with complex 3-D
      data while sharing this information with a larger audience. RESULTS: We have been
      using this system on a routine clinical basis and during neurosurgical training
      courses to collaboratively plan and discuss neurosurgical procedures with 3-D
      reconstructions of patient-specific magnetic resonance and computed tomographic
      imaging data or with a virtual model of the temporal bone. Working
      collaboratively with the 3-D information of a large, interactive, stereoscopic
      projection provides an unambiguous way to analyze and understand the anatomic
      spatial relationships of different surgical corridors. In our experience, the
      system creates a unique forum for open and precise discussion of neurosurgical
      approaches. CONCLUSION: We believe the system provides a highly effective way to
      work with 3-D data in a group, and it significantly enhances teaching of
      neurosurgical anatomy and operative strategies.

PMID- 18091254
TI  - Dividing the posterior communicating artery in approaches to the interpeduncular
      fossa: technical aspects and safety.
AB  - OBJECTIVE: Cutting the posterior communicating artery (PComA) can improve the
      neurosurgeon's view and maneuverability while performing surgery within the
      interpeduncular fossa. Although mentioned in some reports, its technique and
      safety have not been studied in detail thus far. METHODS: Patients undergoing
      surgery for vascular and neoplastic lesions in the interpeduncular fossa in which
      the PComA was cut were retrospectively analyzed regarding the location where the
      PComA was divided, the size of the PComA in relation to the posterior cerebral
      artery, and the vascular risk factors. Clinical and radiological outcomes and the
      related complications were recorded and analyzed. RESULTS: The PComA was divided
      in 25 patients, and was operated on for vascular (in 23 patients) and neoplastic
      (in 2 patients) lesions. The PComA was divided at a perforator-free-zone. This
      zone was most commonly located at the junction of the PComA and the posterior
      cerebral artery (88% of patients). One patient had delayed postoperative bleeding
      from the divided PComA stump. There were no ischemic complications either in the
      territory of the PComA perforator or in the posterior cerebral artery.
      CONCLUSION: This is the largest reported experience with dividing the PComA. It
      shows that this surgical step is safe and that it constitutes an important option
      to help improve the exposure, maneuverability, and safety of surgery in the
      region of the interpeduncular fossa.

PMID- 18091255
TI  - The surgical approach to the posterior cranial fossa according to Galen.
AB  - The surgical approach to the posterior cranial fossa through a straight midline
      incision was adopted in the 1920s. This approach had its forerunner in the
      procedure that Claude Galen adopted and performed on living animals some 1700
      years earlier. Although the mortality rate of those animals cannot be assessed on
      the basis of available information, it was possibly not far off from the
      mortality rates associated with operations performed on the posterior cranial
      fossa in humans at the beginning of the modern surgical era.

PMID- 18091257
TI  - Neuropsychological effects after chronic subthalamic stimulation and the
      topography of the nucleus in Parkinson's disease.
AB  - OBJECTIVE: The neuropsychological effects of chronic subthalamic nucleus (STN)
      deep brain stimulation (DBS) as a treatment for Parkinson's disease are variable.
      Whether these side effects result from the target per se or current diffusion
      into neighboring structures is uncertain. In this study, the relationship between
      clinical outcomes and coordinates of active contact are analyzed and compared
      between patients with and without neuropsychological sequelae. METHODS: Thirty
      eight Parkinsonian patients who underwent bilateral STN-DBS were enrolled in this
      retrospective cohort study. They were followed for at least 12 months. During the
      follow-up period, they were divided into two groups for comparison; Group A
      included patients with neuropsychological side effects and Group B was composed
      of patients without neuropsychological side effects. The position of the active
      contact of the electrode was defined with postoperative magnetic resonance
      imaging scans according to the midcommissural line. Active contact coordinates
      and clinical outcomes were compared for the two groups. RESULTS: Among the 38
      Parkinsonian patients who underwent STN-DBS, eight patients who had
      neuropsychological side effects were assigned to Group A; the other 30 patients
      were assigned to Group B. In Groups A and B, the mean follow-up periods were 13.9
      and 12.1 months, respectively, the Unified Parkinson's Disease Rating Scale motor
      score was improved by 53.4 and 45.2% (P = 0.24), respectively, and the levodopa
      equivalent daily dosage was decreased by 68.4 and 46.4% (P = 0.16), respectively.
      The mean coordinates of active contact in both Groups A and B were x = 10.1 and
      10.5 mm, respectively, y = -2.8 and -3.9 mm, respectively, and z = -6.3 and -6.2
      mm, respectively, relative to the midcommissural point. A significant difference
      was observed on the y axis (P = 0.01). CONCLUSION: When taking spatial influence
      into consideration, the neuropsychological effects of chronic STN-DBS were
      related to a significant anteriorly located active contact within the ventral STN
      in this preliminary study. This might suggest the existence of topography of STN
      in patients with Parkinson's disease concerning limbic and associative circuits.

PMID- 18091258
TI  - Extracranial aneurysm of the posterior inferior cerebellar artery with an
      aberrant origination: case report.
AB  - OBJECTIVE: Aneurysms of the extracranially originating posterior inferior
      cerebellar artery are very rare. An anatomic insight of its possible course and
      variations is necessary when confronting such extraordinary lesions. CLINICAL
      PRESENTATION: A 19-year-old man presented with the sudden onset of severe
      headaches. A physical examination was positive only for neck rigidity. Computed
      tomographic scans of the brain depicted intraventricular hemorrhage. TECHNIQUE
      AND INTERVENTION: Four-vessel brain digital subtraction angiography revealed an
      extracranial posterior inferior cerebellar artery arising extradurally from the
      right vertebral artery between the C1 and C2 vertebrae, bearing a saccular
      aneurysm in an upper cervical intradural location. An anterior inferior
      cerebellar artery-posterior inferior cerebellar artery variant was also found on
      the left side. Computed tomographic angiography failed to unmask the lesion. The
      aneurysm was clipped through a suboccipital craniectomy and C1 laminectomy.
      CONCLUSION: The patient did well after surgery and was discharged from the
      hospital without neurological deficit. One can conclude that a comprehensive
      diagnostic approach oriented to the patient history and clinical data is
      mandatory to preclude such lesions evading the vigilant surgeon.

PMID- 18091259
TI  - Radiation-induced tumor after stereotactic radiosurgery for an arteriovenous
      malformation: case report.
AB  - OBJECTIVE: To present a rare case of a radiation-induced malignancy after
      stereotactic radiosurgery. CLINICAL PRESENTATION: A 34-year-old woman presented
      with headaches. Imaging studies demonstrated a 4.5-cm arteriovenous malformation
      located in the pineal region. She was treated with a two-isocenter plan to a
      total dose of 1500 cGy prescribed to the 70% isodose line. She was lost to follow
      up and presented with a change in mental status, nausea, headaches, and a
      generalized seizure 9 years later. Magnetic resonance imaging scans demonstrated
      a large, heterogeneously enhancing mass partially in the treatment volume.
      INTERVENTION: Surgical debulking demonstrated an infiltrating glial neoplasm
      consistent with a glioblastoma multiforme. There was no staining for epidermal
      growth factor receptor, whereas greater than 75% of nuclei stained positively
      with p53. CONCLUSION: The risk of radiation-induced tumors is currently unknown
      but needs to be determined to assess the risk-benefit profile for each patient.

PMID- 18091260
TI  - Vertical gaze palsy after thalamic stimulation for Tourette syndrome: case
      report.
AB  - OBJECTIVE: We describe a patient who developed a vertical gaze paralysis after
      deep brain stimulation performed for intractable Tourette syndrome due to a small
      deep bleeding in the upper mesencephalon. CLINICAL PRESENTATION: A 39-year-old
      man underwent thalamic deep brain stimulation for intractable Tourette syndrome.
      Immediately postoperatively, he had diplopia and dizziness. The neurological
      examination revealed vertical gaze palsy with preserved vertical oculocephalic
      movements. A postoperative computed tomography scan revealed a discrete high
      density lesion across the midline at the distal end of the left electrode. This
      area corresponds with the pretectal area, including the rostral interstitial
      nucleus of the medial longitudinal fasciculus, with sparing of the oculomotor and
      rubral nuclei. INTERVENTION: Six months postoperatively, maximal upward and
      downward smooth pursuit eye movements were achieved. Upward saccadic velocities
      were still reduced by 20 to 25 degrees. CONCLUSION: This case report describes a
      complication that might demand special attention during the planning of thalamic
      deep brain stimulation for the treatment of Tourette syndrome. Examination of
      both horizontal and vertical eye movements during deep brain stimulation surgery
      is recommended.

PMID- 18091261
TI  - Fluorescence of non-neoplastic, magnetic resonance imaging-enhancing tissue by 5
      aminolevulinic acid: case report.
AB  - OBJECTIVE: It has been established that fluorescence-guided resection using 5
      aminolevulinic acid is useful in glioma surgery. In this study, we describe three
      cases in which even perinecrotic tissue could be recognized as fluorescence
      positive. METHODS: Three cases of central nervous system disease, showing
      gadolinium enhancement on magnetic resonance imaging scans, were operated on with
      the aid of fluorescence derived from 5-aminolevulinic acid. Two of these were
      diagnosed as radiation necrosis and the other as a neurodegenerative
      demyelinating disease. RESULTS: In all cases, at least some parts of the
      gadolinium-enhanced area could be labeled as fluorescence positive, whereas
      centers of necrotic tissue were negative for fluorescence. Histologically, cell
      infiltration was marked in each case that showed fluorescence activity.
      CONCLUSION: Both malignant tumors and the perinecrotic area in radiation necrosis
      or neurodegenerative disease can be labeled as fluorescence positive using 5
      aminolevulinic acid.

PMID- 18091262
TI  - Regeneration of peripheral motor nerve gaps with a polyglycolic acid-collagen
      tube: technical case report.
AB  - OBJECTIVE: After previous success in regenerating canine peripheral nerves over
      80 mm gaps using a bioabsorbable nerve guide tube, we have extended this method
      to the treatment of patients experiencing various types of nerve injury. This
      report describes the treatment of two cases of motor nerve disorder. METHODS: The
      bioabsorbable nerve tube was a cylindrically woven polyglycolic acid (PGA) tube
      filled with collagen. A peripheral motor nerve defect (the frontalis branch of
      the facial nerve) was reconstructed using this PGA-collagen tube in two patients
      who experienced posttraumatic unilateral eyebrow ptosis for 3 months. RESULTS:
      Five months after surgery, both patients regained their ability to voluntarily
      lift their eyebrows symmetrically. Electrophysiological examination at 5 months
      revealed recovery of compound muscle action potential and disappearance of distal
      latency on the affected side. CONCLUSION: This is the first clinical report of
      motor nerve recovery achieved using the PGA-collagen nerve guide tube. The
      results suggest that use of a PGA-collagen tube is a promising option for the
      repair of motor nerve defects.

PMID- 18091265
TI  - The Nobel Prize 1901.

PMID- 18091264
TI  - The nobel prize: recognizing those who "conferred the greatest benefit on
      mankind".

PMID- 18091266
TI  - The brain on itself: Nobel laureates and the history of fundamental nervous
      system function.
AB  - The Nobel Prize in Physiology or Medicine has been given in recognition of work
      in the neurosciences a number of times. Laureates have been awarded for work on
      both fundamental and more complex nervous system functions. This review is
      restricted to contributions by 20th century laureates to the understanding of
      fundamental nervous system function on the cellular level. In 1906, Camillo Golgi
      and Ramon y Cajal were awarded for their work on the microscopic structure of the
      nervous system. Their achievement and those of others within this field, coupled
      with technological progress, gradually allowed more complex physiological
      studies. In 1932, the prize was awarded to Charles Sherrington and Edgar Adrian
      for their discoveries of how neurons function. They were followed in 1944 by
      Herbert Gasser and Joseph Erlanger who uncovered the highly differentiated
      functions of single nerve fibers. Alan Hodgkin and Andrew Huxley were awarded for
      the detection of the ionic mechanism of the action potential and its mathematical
      explanation in 1963. In 1991, Erwin Neher and Bernd Sakmann were awarded for
      their work on single ion channels. Although the scientists who proved the
      hypothesis (Fridjof Nansen, Wilhelm His, and August Forel) were never awarded by
      the Nobel Committee, their studies gave rise to one of the most fundamental
      questions in 20th century neuroscience: How is information carried from one
      neuron to another or to an effector cell? This was first solved in the vegetative
      nervous system, and, in 1936, Henry Dale and Otto Loewi received the prize for
      their discoveries relating to chemical transmission of nerve impulses. In 1963,
      John Eccles was awarded the prize for his work on the physiology of synapses. In
      1970, Bernhard Katz received the Nobel Prize for the discovery of quantal
      release. Katz shared the prize with Julius Axelrod and Ulf von Euler, who were
      central in finding that transmitters are stored in presynaptic vesicles and that
      the effect in many synapses is terminated by reuptake. This review does not
      include 21st century laureates, although the prize has already been given to
      neuroscientists twice this century; Arvid Carlsson, Paul Greengard, and Eric
      Kandel received the award in 2000 for their discoveries related to signal
      transduction, and Richard Axel and Linda Buck received the award in 2004 for
      their work in the field of odorant receptors and the organization of the
      olfactory system.

PMID- 18091267
TI  - Management of distal anterior cerebral artery aneurysms: a single institution
      retrospective analysis (1997-2005).
AB  - OBJECTIVE: Our goal was to assess the clinical and angiographic outcomes among
      patients undergoing treatment for distal anterior cerebral artery aneurysms at
      the Jefferson Hospital for Neuroscience (1997-2005). METHODS: Forty-one patients
      (1.5% of all aneurysms treated) with distal anterior cerebral artery aneurysms
      had undergone treatment. The clinical and angiographic outcomes of these patients
      were studied retrospectively using chart reviews, operative reports, and
      angiographic reports. The mean clinical and angiographic follow-up periods were
      16 months (range, 3-74 mo) and 16.5 months (range, 6-81 mo), respectively.
      RESULTS: Twenty-eight (68%) patients had undergone endovascular embolization (22
      women, six men; mean age, 58.2 yr), whereas 13 (32%) had undergone microsurgery
      for clip ligation (six men, seven women; mean age, 47.4 yr). Within the coiled
      group, 50% of the patients belonged in the Hunt and Hess (HH) III and IV groups,
      whereas 46.2% of the patients in the clipped group were elective patients (HH
      Grade 0). The mean aneurysmal sizes among the clipped and coiled groups were 4.9
      and 5.5 mm, respectively. Among the clipped patient population, 100% of the
      patients had successful clip ligation as evidenced by intraoperative cerebral
      angiography, there was a 0% recurrence rate among the two patients who have had
      long-term follow-up, 0% recurrent subarachnoid hemorrhage, and 92% patients
      achieved a modified Glasgow Outcome Scale score of I to II. Among the coiled
      patient population, there was an 89% rate of successful embolization, 18%
      recurrence rate, 0% recurrent subarachnoid hemorrhage, and 64% achieved a
      modified Glasgow Outcome Scale score of I to II. None of the patients had
      clinically symptomatic vasospasm. A strong correlation existed between having a
      ventriculostomy and requiring a shunt in patients with HH Grade IV compared with
      patients in HH Grades I through III. CONCLUSION: In our analysis, clinical
      outcomes were better in the clipped group; however, the differences are not
      statistically significant (P = 0.3675) and are explained by the selection bias.
      Statistically significant predictors of outcomes were age (<60 yr), size of the
      aneurysm (>5 mm), absence of ventriculostomy, and presenting HH grade.

PMID- 18091268
TI  - Anosmia after aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Anosmia has an important impact on well-being but is often neglected
      by physicians. In patients with subarachnoid hemorrhage (SAH), anosmia has mainly
      been reported after surgery for aneurysms of the anterior communicating artery.
      We studied the prevalence, predisposing factors (aneurysm site and type of
      treatment), impact, and prognosis of anosmia in patients with SAH. METHODS: Of
      the patients with SAH who resumed independent living, we included all patients
      treated by coiling between 1997 and 2003 and a sample of patients treated by
      clipping between 1985 and 2001. Patients underwent structured interviews
      regarding the presence and duration of anosmia. The impact of anosmia was scored
      using a visual analog scale ranging from 0 (no influence) to 100 (the worst thing
      that ever happened to them). Risk factors for anosmia were assessed by logistic
      regression analysis. RESULTS: Overall, 89 of the 315 interviewed patients (28%;
      95% confidence interval [CI], 23-34%) reported anosmia after SAH (mean follow-up
      period, 7.4 yr), including 10 (15%) of the 67 coiled patients and 79 (32%) of the
      248 clipped patients. The median visual analog scale impact score was 53 (range,
      0-100). In 20 of the 89 patients (23%; 95% CI, 15-33), the symptoms had improved
      over time. Risk factors for anosmia were treatment by clipping (odds ratio [OR],
      2.7; 95% CI, 1.3-5.7) and anterior communicating artery aneurysms (OR, 2.0; 95%
      CI, 1.2-3.3). CONCLUSION: Anosmia after SAH has a high prevalence, considerable
      impact, and poor prognosis. Its occurrence after coiling suggests not only damage
      to the olfactory nerve by clipping but also that the SAH itself plays a role in
      its pathogenesis.

PMID- 18091269
TI  - Risk of shunt-dependent hydrocephalus after occlusion of ruptured intracranial
      aneurysms by surgical clipping or endovascular coiling: a single-institution
      series and meta-analysis.
AB  - OBJECTIVE: To compare the risk of shunt-dependent hydrocephalus after treatment
      of ruptured intracranial aneurysms by clipping versus coiling. METHODS: We
      analyzed 596 patients prospectively added to our database from July of 1999 to
      November of 2005 concerning the risk of shunt dependency after clipping versus
      coiling. Factors analyzed included age; sex; Hunt and Hess grade; Fisher grade;
      acute hydrocephalus; intraventricular hemorrhage; angiographic vasospasm; and
      number, size, and location of aneurysms. In addition, a meta-analysis of
      available data from the literature was performed identifying four studies with
      quantitative data on the frequency of clip, coil, and shunt dependency. RESULTS:
      The institutional series revealed Hunt and Hess grade, Fisher grade, acute
      hydrocephalus, intraventricular hemorrhage, and angiographic vasospasm as
      significant (P < 0.05) risk factors for shunt dependency after a univariate
      analysis. In a multivariate logistic regression analysis, we isolated
      intraventricular hemorrhage, acute hydrocephalus, and angiographic vasospasm as
      independent, significant risk factors for shunt dependency. The meta-analysis,
      including the current data, revealed a significantly higher risk for shunt
      dependency after coiling than after clipping (P = 0.01). CONCLUSION: Clipping of
      a ruptured aneurysm may be associated with a lower risk for developing shunt
      dependency, possibly by clot removal. This might influence long-term outcome and
      surgical decision making.

PMID- 18091270
TI  - Clinical evaluation and follow-up outcome of diffusion tensor imaging-based
      functional neuronavigation: a prospective, controlled study in patients with
      gliomas involving pyramidal tracts.
AB  - OBJECTIVE: To evaluate diffusion tensor imaging (DTI)-based functional
      neuronavigation in surgery of cerebral gliomas with pyramidal tract (PT)
      involvement with respect to both perioperative assessment and follow-up outcome.
      METHODS: A prospective, randomized controlled study was conducted between 2001
      and 2005. A consecutive series of 238 eligible patients with initial imaging
      diagnosis of cerebral gliomas involving PTs were randomized into study (n = 118)
      and control (n = 120) groups. The study cases underwent DTI and three-dimensional
      magnetic resonance imaging scans. The maps of fractional anisotropy were
      calculated for PT mapping. Both three-dimensional magnetic resonance imaging data
      sets and fractional anisotropy maps were integrated by rigid registration, after
      which the tumor and adjacent PT were segmented and reconstructed for presurgical
      planning and intraoperative guidance. The control cases were operated on using
      routine neuronavigation. RESULTS: There was a trend for high-grade gliomas (HGGs)
      in the study group to be more likely to achieve gross total resection (74.4
      versus 33.3%, P < 0.001). There was no significant difference of low-grade
      gliomas resection between the two groups. Postoperative motor deterioration
      occurred in 32.8% of control cases, whereas it occurred in only 15.3% of the
      study cases (P < 0.001). The 6-month Karnofsky Performance Scale score of study
      cases was significantly higher than that of control cases (86 +/- 20 versus 74 +/
      28 overall, P < 0.001; 93 +/- 10 versus 86 +/- 17 for low-grade gliomas, P =
      0.013; and 77 +/- 27 versus 53 +/- 32 for HGGs, P = 0.001). For 81 HGGs, the
      median survival of study cases was 21.2 months (95% confidence interval, 14.1
      28.3 mo) compared with 14.0 months (95% confidence interval, 10.2-17.8 mo) of
      control cases (P = 0.048). The estimated hazard ratio for the effect of DTI-based
      functional neuronavigation was 0.570, representing a 43.0% reduction in the risk
      of death. CONCLUSION: DTI-based functional neuronavigation contributes to maximal
      safe resection of cerebral gliomas with PT involvement, thereby decreasing
      postoperative motor deficits for both HGGs and low-grade gliomas while increasing
      high-quality survival for HGGs.

PMID- 18091271
TI  - Intracranial meningioma surgery in the ninth decade of life.
AB  - OBJECTIVE: The aims of this study are to assess the surgical outcome of elderly
      patients aged 80 years or more, to analyze the factors influencing postoperative
      course, and to propose a grading system to standardize the surgical indication of
      intracranial meningioma in the elderly. METHODS: Between 1990 and 2005, we
      surgically treated 74 consecutive patients aged 80 years or more for intracranial
      meningiomas (47 women, 27 men; mean age, 82 yr; age range, 80-90 yr). The median
      follow-up period was 94 months (range, 15-147 mo). We retrospectively analyzed
      the factors influencing surgical outcome and retained the significant factors to
      form the Sex, Karnofsky Performance Scale, American Society of Anesthesiology
      Class, Location of Tumor, and Peritumoral Edema (SKALE) grading system. RESULTS:
      There was no perioperative mortality, and the 1-year mortality rate was 9.4%.
      Postoperative mortality was lower in women with a Karnofsky Performance Scale
      score of 60 or greater, an American Society of Anesthesiology Class of 1 or 2, a
      noncritical tumor location, and a moderate or absent peritumoral edema. Patients
      with a SKALE score of more than 8 had an excellent outcome, whereas those with a
      SKALE score of less than 8 had a poor outcome. The rate of postoperative
      complications was 9.4%. Large tumors, critical locations, severe peritumoral
      edema, and total surgical excision were associated with a higher risk of
      postoperative complications. CONCLUSION: Surgery of intracranial meningioma in
      elderly patients is feasible when the SKALE score is 8 or greater. Prospective
      studies are required to validate this grading system.

PMID- 18091272
TI  - Clinical relevance of precipitating factors in pituitary apoplexy.
AB  - OBJECTIVE: The pathogenesis of pituitary apoplexy and the role of precipitating
      factors in pituitary apoplexy are poorly understood. Most of the published cases
      are in the form of case reports. We assessed the presumed precipitating factors
      in a series of patients treated surgically for pituitary apoplexy and reviewed
      the contemporary published literature. METHOD: Thirty-eight consecutive patients
      with pituitary apoplexy were treated surgically by the Department of Neurosurgery
      at the University of Virginia, Charlottesville, VA, between January 1996 and
      March 2006. Their medical records were retrospectively reviewed. Contemporary
      published cases from 1990 to 2006 were also reviewed. RESULTS: Nine patients
      (24%) were identified as having precipitating factors for pituitary apoplexy. The
      factors identified were coronary artery surgery (two patients), other major
      surgery (two patients), pregnancy (two patients), gamma knife irradiation,
      anticoagulant therapy, and coagulopathy secondary to liver failure. The
      presentation, histology, and outcome were compared between those patients with a
      precipitating factor and those in whom none was identified. A review of the
      published literature showed that coronary artery surgery, pituitary stimulation,
      and coagulopathy were the most common precipitating factors. CONCLUSION: A
      minority of patients with pituitary apoplexy will have precipitating factors. The
      majority of patients with precipitating factors will have histopathology showing
      hemorrhagic infarction or hemorrhage. The most common precipitating factors are
      pituitary stimulation, surgery, particularly coronary artery surgery, and
      coagulopathy. Caution in doing endocrine investigation, surgery, or
      anticoagulation in patients with a known pituitary tumor is advised. Patients
      with no diagnosed pituitary tumor but with a known precipitating factor who have
      neuro-ophthalmological deterioration or endocrine failure should undergo prompt
      magnetic resonance image scans and endocrine investigation and endocrine
      replacement as indicated.

PMID- 18091273
TI  - Multilevel anterior cervical fusion using a collagen-hydroxyapatite matrix with
      iliac crest bone marrow aspirate: an 18-month follow-up study.
AB  - OBJECTIVE: The pseudarthrosis rate after multisegment anterior cervical fusion is
      directly related to the number of levels surgically fused. The advent of
      osteobiological adjuvants offers an opportunity to reduce both the likelihood of
      failed arthrodesis and the need for posterior instrumentation. Collagen
      hydroxyapatite matrix is osteoconductive and has been used with autogenous bone
      marrow aspirate (BMA) to promote fusion. We report our results of using collagen
      hydroxyapatite matrix with BMA for multilevel anterior cervical discectomy and
      fusion and anterior cervical corpectomy and fusion (ACCF). METHODS: Sixty-six
      consecutively treated patients underwent a multilevel anterior cervical
      discectomy and fusion and/or ACCF during a period of 16 months. In all cases, a
      Smith-Robinson decompression was performed followed by allograft fibula strut
      grafting filled with collagen-hydroxyapatite matrix and BMA, and anterior
      semiconstrained cervical plating. A vacuum chamber was used to draw the BMA
      slowly through the collagen-hydroxyapatite sponges. No patient underwent
      simultaneous posterior instrumentation. Clinical outcome was determined by an
      independent observer who evaluated patients on the basis of symptom and
      neurological examination results. Radiographic fusion was determined by dynamic x
      rays and computed tomographic scanning during an 18-month follow-up period.
      RESULTS: With the inclusion of discectomies performed in ACCF procedures,
      patients were fused between two and five disc levels (mean, 3.1 levels).
      Seventeen patients underwent one to four-level corpectomies (mean, two levels).
      Clinical improvement was observed in 49 patients. Conditions in nine patients
      remained unchanged, and two patients had radicular palsies. In all, 60 patients
      were followed and analyzed for radiographic fusion. All but two patients
      demonstrated successful radiographic fusion. CONCLUSION: Collagen-hydroxyapatite
      matrix with BMA can be a safe, effective adjuvant for promoting fusion in
      multilevel anterior cervical discectomy and fusion and ACCF. Although randomized,
      controlled studies are necessary to determine whether or not the fusion rates are
      superior to those obtained from using allograft alone, these results compare
      favorably to historical data in the literature.

PMID- 18091274
TI  - Microsurgical cervical nerve root decompression via an anterolateral approach:
      clinical outcome of patients treated for spondylotic radiculopathy.
AB  - OBJECTIVE: We previously reported our technique of selective microforaminotomy
      via an anterolateral approach for the treatment of spondylotic radiculopathy. We
      now report the clinical long-term results. METHODS: A retrospective study of 40
      patients who consecutively underwent operation via this technique was performed.
      Patients' demographic, clinical presentation, and radiological and surgical data
      were recorded by chart review. Long-term clinical outcome was assessed by a
      questionnaire, office visits, and intensive telephone interviews. The results
      were compared with the literature. RESULTS: The study was comprised of 22 women
      and 18 men with a mean age of 50.6 years (age range, 33.1-75.2 yr).
      Preoperatively, 98% (n = 39) of the patients presented radicular pain, 88% (n =
      35) of the patients presented with neck pain, 75% (n = 30) of the patients
      presented with a sensory deficit, and 45% (n = 18) of the patients presented with
      a motor deficit. Patients underwent operation at one level (n = 15), two levels
      (n = 23), or three levels (n = 2). One patient underwent operation bilaterally in
      a two-step procedure. In total, 68 cervical nerve roots were completely
      decompressed by this technique. On the basis of preoperative x-ray criteria of
      instability, two patients (5%) required graft arthrodesis, which was performed
      during the same surgery after the nerve root decompression. After a mean follow
      up period of 4.3 years (range, 2.7-7.4 yr), 85% of the patients have no residual
      radicular pain, 94% of the patients have no more neck pain, 90% of the patients
      recovered from their sensory deficits, and 83% of the patients recovered from
      their motor deficits. According to Odom's criteria, 95% achieved an excellent or
      good outcome (Odom Grades I and II). No postoperative instability occurred. The
      transient and permanent morbidity rates were 7.5% (n = 3) and 2.5% (n = 1),
      respectively; one patient has permanent Horner's syndrome. CONCLUSION: The
      technique of microsurgical cervical nerve root decompression by selective
      microforaminotomy via an anterolateral approach is safe and efficient for the
      treatment of spondylotic radiculopathy. The morbidity rate is low. Clinical
      results are good after a long-term follow-up period. This technique allows the
      preservation of cervical motion and spinal stability. The results compare
      favorably to those of the literature.

PMID- 18091275
TI  - Spinopelvic alignment of patients with degenerative spondylolisthesis.
AB  - OBJECTIVE: The main objectives of this study were to analyze and compare
      spinopelvic parameters, including the pelvis shape, in a population of 40
      patients with degenerative spondylolisthesis (DSPL) and to compare these patients
      with a control group of asymptomatic volunteers. METHODS: Forty patients with
      DSPL were included in this study. Spinopelvic parameters were analyzed on
      preoperative full spine x-rays in a standardized standing position. The following
      spinopelvic parameters were measured: pelvic incidence (PI), sacral slope, pelvic
      tilt, lumbar lordosis, thoracic kyphosis, and positioning of the C7 plumb line.
      The population of patients was compared with a control population of 154 normal
      and asymptomatic adults who were studied in a recently published study. In order
      to understand variations of spinopelvic parameters, a control group was matched
      according to the PI, which is a morphological parameter. RESULTS: The PI was
      significantly greater for patients with DSPL (60.1 +/- 10.6 degrees) compared
      with the control group (52 +/- 10.7 degrees) (P < 0.0005). After matching
      according to the pelvic incidence, the DSPL population was characterized by an
      anterior translation of the C7 plumb line (P < 0.05), a loss of lumbar lordosis
      (P < 0.0005), and a decrease of the sacral slope (P < 0.0005). Retrolisthesis
      and/or segmental intervertebral hyperextension were observed in the upper lumbar
      spine in 30% of the cases. CONCLUSION: Matching according to the PI between the
      patients in the study and the control group enabled us to understand variations
      of the spinopelvic parameters in a population of patients with DSPL. DSPL
      patients were characterized by a greater PI than the asymptomatic population;
      therefore, we suggest that a high PI may be a predisposing factor in developing
      DSPL. Finally, we observed significant variations in spinopelvic alignment, such
      as loss of lordosis and sagittal unbalance, which were partially compensated by
      pelvis back tilt and hyperextension in the upper lumbar spine.

PMID- 18091276
TI  - A clinical scoring system for neurological assessment of high cervical
      myelopathy: measurements in pediatric patients with congenital atlantoaxial
      dislocations.
AB  - OBJECTIVE: The assessment of response to treatment in pediatric patients with
      congenital atlantoaxial dislocation (AAD) is performed using a disability grading
      system but may be better determined by a score based on clinical parameters. This
      study proposes a scoring system based on a comprehensive neurological examination
      to assess surgical outcome in these patients. METHODS: Sixty-seven patients with
      congenital AAD aged 14 years or younger were included and analyzed prospectively.
      A scoring system based on six factors (motor power, gait, sensory involvement,
      sphincteric involvement, spasticity, and respiratory difficulty) was designed at
      the beginning of the study and all patients were assessed using this score as
      well as the Di Lorenzo's grade preoperatively, postoperatively, and at the time
      of each follow-up visit. RESULTS: There was a very high incidence of
      occipitalized arch of atlas and fusion of the second and third cervical vertebrae
      in the irreducible variety. Most patients were classified in poor grades
      preoperatively; however, the changes in score were seen more often when using the
      scoring system we developed compared with the Di Lorenzo's grade. Our score also
      corroborated better with the clinical improvement. CONCLUSION: The clinical
      profiles of pediatric patients with AAD are similar with a higher incidence of
      atlas arch anomalies in patients with irreducible AAD. A scoring system based on
      clinical parameters is proposed for clinical evaluation of such patients. This
      system is easy to use and interpret and is more sensitive to the changes in the
      neurological status of patients.

PMID- 18091277
TI  - Atlanto-occipital dislocation--part 2: The clinical use of (occipital) condyle-C1
      interval, comparison with other diagnostic methods, and the manifestation,
      management, and outcome of atlanto-occipital dislocation in children.
AB  - OBJECTIVE: The diagnosis of atlanto-occipital dislocation (AOD) remains
      problematic as a result of a lack of reliable radiodiagnostic criteria. In Part 1
      of the AOD series, we showed that the normal occiput-C1 joint in children has an
      extremely narrow joint gap (condyle-C1 interval [CCI]) with great left-right
      symmetry. In Part 2, we used a CCI of 4 mm or greater measured on reformatted
      computed tomographic (CT) scans as the indicator for AOD and tested the
      diagnostic sensitivity and specificity of CCI against published criteria. The
      clinical manifestation, neuroimaging findings, management, and outcome of our
      series of patients with AOD are also reported. METHOD: For diagnostic
      sensitivity, we applied the CCI criterion on 16 patients who fulfilled one or
      more accepted radiodiagnostic criteria of AOD and who showed clinical and imaging
      hallmarks of the syndrome. All 16 patients had plain cervical spine x-rays, head
      CT scans, axial cervical spine CT scans with reconstruction, and magnetic
      resonance imaging scans. The diagnostic yield and false-negative rate of CCI were
      compared with those of four published "standard" tests, namely Wholey's dens
      basion interval, Powers' ratio, Harris' basion-axis interval, and Sun's
      interspinous ratio. The diagnostic value of "nonstandard" indicators such as
      cervicomedullary deficits, tectorial membrane and other ligamentous damage,
      perimedullary subarachnoid hemorrhage, and extra-axial blood at C1-C2 were also
      assessed. For diagnostic specificity, we applied CCI and the "standard" and
      "nonstandard" tests on 10 patients from five classes of non-AOD upper cervical
      injuries. The false-positive diagnostic rates for AOD of all respective tests
      were documented. RESULTS: The CCI criterion was positive in all 16 patients with
      AOD with a diagnostic sensitivity of 100%. Fourteen patients had bilateral AOD
      with disruption and widening of both OC1 joints. Two patients had unilateral AOD
      with only one joint wider than 4 mm. The abnormal CCI varied from 5 to 34 mm.
      Eight patients showed blatant left-right joint asymmetry in either CCI or
      anatomic conformation. The diagnostic sensitivities for the "standard" tests are
      as follows: Wholey's, 50%; Powers', 37.5%; Harris', 31%; and Sun's, 25%, with
      false-negative rates of 50, 62.5, 69, and 75%, respectively. The sensitivities
      for the "nonstandard" indicators are: tectorial membrane damage, 71%;
      perimedullary blood, 63%; and C1-C2 extra-axial blood, 75%, with false-negative
      rates of 29, 37, and 25%, respectively. Fifteen patients with AOD had occiput
      cervical fusion. There were one early and two delayed deaths (19% mortality); two
      patients (12%) had complete or severe residual high quadriplegia, but 11 children
      (69%) enjoyed excellent neurological recovery. CCI was normal in all 10 patients
      with non-AOD upper cervical injuries with a diagnostic specificity of 100%. The
      false-positive rates for the four "standard" tests were: Sun's, 60%; Harris',
      50%; Wholey's, 30%; and Powers', 10%; for the "nonstandard" indicator, the rates
      were: cervicomedullary deficits, 70%; tectorial membrane damage, 40%; C1-C2 extra
      axial blood, 40%; and perimedullary blood, 30%. CONCLUSION: The CCI criterion has
      the highest diagnostic sensitivity and specificity for AOD among all other
      radiodiagnostic criteria and indicators. CCI is easily computed from
      reconstructed CT scans, has almost no logistical or technical distortions, can
      capture occiput-C1 joint dislocation in all three planes, and is unaffected by
      congenital anomalies or maturation changes of adjacent structures. Because CCI is
      the only test that directly measures the integrity of the actual joint injured in
      AOD and a widened CCI cannot be concealed by postinjury changes in the head and
      neck relationship, it surpasses others that use changeable landmarks.

PMID- 18091278
TI  - Functional outcome of brachial plexus reconstruction after trauma.
AB  - OBJECTIVE: Traumatic brachial plexopathies can be devastating injuries. In
      addition to motor and sensory deficits, pain and functional limitations can be
      equally debilitating. We sought to evaluate functional outcome and quality of
      life using statistically validated tools. METHODS: The authors identified a
      consecutive series of patients who underwent surgical repair of a brachial plexus
      injury by the same surgeon between 1997 and 2004 at the McGill University Health
      Center. Participating patients were sent a package containing the Short Form 36,
      the Disability of the Arm, Shoulder, and Hand questionnaire, a pain visual analog
      scale, and an additional question on their satisfaction with the surgery. Data
      was recorded and analyzed using statistical software (SPSS version 13.0 for
      Windows; SPSS, Inc., Chicago, IL). RESULTS: Thirty-one patients with a mean age
      of 32.7 years at the time of injury participated in this study. The mean time to
      surgery was 7.5 months, and the mean follow-up period was 42.7 months. Patients
      who underwent surgery within 6 months of injury scored consistently better on the
      Disability of the Arm, Shoulder, and Hand questionnaire (P = 0.03) and the Short
      Form 36 subscale scores. There was no difference between supra- and
      infraclavicular injuries; however, patients with root avulsion injuries were more
      likely to have pain (P = 0.04) and scored lower on the Disability of the Arm,
      Shoulder, and Hand questionnaire (P = 0.05). CONCLUSION: Statistically validated
      tools can be used to evaluate the quality of life, upper extremity function, and
      pain after brachial plexus repairs. Root avulsion injuries and delayed surgical
      repair correlated negatively with functional outcomes.

PMID- 18091279
TI  - Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR)
      followed by radiation therapy with and without temozolomide in newly diagnosed
      malignant gliomas: phase 1 study of final safety results.
AB  - OBJECTIVE: Cintredekin besudotox (CB), a recombinant cytotoxin consisting of
      interleukin-13 and truncated Pseudomonas exotoxin, binds selectively to
      interleukin-13R alpha2 receptors overexpressed by malignant gliomas. This study
      assessed the safety of CB administered by convection-enhanced delivery followed
      by standard external beam radiation therapy (EBRT) with or without temozolomide
      (Temodar; Schering-Plough, Kenilworth, NJ) in patients with newly diagnosed
      malignant gliomas. METHODS: After gross total resection of the tumor, two to four
      intraparenchymal catheters were stereotactically placed and CB (0.25 or 0.5
      microg/mL) was infused for 96 hours. This was followed, 10 to 14 days later, by
      EBRT (5940-6100 cGy, 5 d/wk for 6-7 wk) with or without temozolomide (75 mg/m/d,
      7 d/wk during EBRT). Safety was assessed during an 11-week observation period
      after catheter placement RESULTS: Twenty-two patients (12 men, 10 women; median
      age, 55 yr; 21 with glioblastoma multiforme and one with an anaplastic mixed
      oligoastrocytoma) were enrolled. None of the patients experienced dose-limiting
      toxicities in the first two cohorts (0.25 microg/mL CB + EBRT [n = 3] and 0.25
      microg/mL CB + EBRT + temozolomide [n = 3]). One patient experienced a dose
      limiting toxicity (Grade 4 seizure) in the third cohort (0.5 microg/mL CB + EBRT
      [n = 6]). Six patients in the final cohort (0.5 microg/mL CB + EBRT +
      temozolomide [n = 10]) completed treatment, and one patient experienced a dose
      limiting toxicity (Grade 3 aphasia and confusion). Four patients were not
      considered evaluable for a dose decision and were replaced. CB related adverse
      events occurring in more than one patient were fatigue, gait disturbance,
      nystagmus, and confusion. No Grade 3 to 4 hematological toxicities were observed.
      CONCLUSION: CB (0.5 microg/mL) administered via convection-enhanced delivery
      before standard radiochemotherapy seems to be well tolerated in adults with newly
      diagnosed malignant gliomas. Further clinical study assessment is warranted.

PMID- 18091280
TI  - A survey to determine the understanding of the conceptual basis and diagnostic
      tests used for brain death by neurosurgeons in Canada.
AB  - OBJECTIVE: To determine the understanding of the conceptual basis and diagnostic
      tests used for brain death (BD) by neurosurgeons in Canada. METHODS: Between
      February and June 2006, a previously developed survey was mailed to every
      neurosurgeon in Canada. RESULTS: Of 223 surveys mailed, 147 (66%) were returned;
      of these, 128 (87%) were completed and analyzed. When asked to choose a
      conceptual reason to explain why BD is equivalent to death, 50 (39%) chose a
      higher brain concept, 50 (39%) chose a prognosis concept, and 33 (26%) chose a
      loss of integration of the organism concept. More than half of respondents
      answered that BD is not compatible with electroencephalographic activity or
      brainstem evoked potential activity. More than one-third of respondents answered
      that some cerebral blood flow or a brainstem with minimal microscopic damage was
      not compatible with BD. Of the 90 respondents who answered that they were
      comfortable diagnosing BD because the conceptual basis of BD makes it equivalent
      to death of the patient, in their own words, 14 (16%) used a loss of integration
      concept, 20 (22%) used a prognosis concept, 25 (28%) used a higher brain concept,
      and 39 (43%) did not articulate a concept. When asked, "Are brain death and
      cardiac death the same state (i.e., are both death of the patient)?," 57 (45%)
      answered "No." CONCLUSION: Within the neurosurgical community, a stand-alone
      concept of BD does not exist. There is also significant variability in the
      understanding of the tests that are compatible with the criterion of BD.

PMID- 18091281
TI  - Fluorescent in situ hybridization and ex vivo 1H magnetic resonance spectroscopic
      examinations of meningioma tumor tissue: is it possible to identify a clinically
      aggressive subset of benign meningiomas?
AB  - OBJECTIVE: Although histologically benign, Grade I meningiomas can sometimes
      behave aggressively. The clinically-aggressive subset of Grade I meningiomas is
      typically indistinguishable from clinically-benign Grade I meningiomas in vivo.
      We compared molecular genetic and biochemical findings to clinical, pathological,
      and immunohistochemical information in a series of clinically-aggressive Grade I
      meningiomas with a series of clinically-benign meningiomas to identify
      characteristics that may be used to distinguish between these two groups.
      METHODS: Tumor tissue samples from 30 patients with Grade I meningiomas were
      harvested. Half of the sample was embedded in paraffin to be used for fluorescent
      in situ hybridization to examine aberrations of chromosomes 1p, 14q, and 22q; the
      other half was snap frozen and examined with proton magnetic resonance
      spectroscopy to identify concentrations of key metabolites in the tissue ex vivo.
      Clinical and pathological parameters were retrospectively reviewed as part of
      routine clinical management. These data were evaluated for potential unique
      associations with diagnostic significance. RESULTS: Molecular genetic and
      biochemical findings correlated with clinical behavior of the two Grade I
      meningioma groups. Specific chromosomal abnormalities correlated with the
      aggressive phenotype: homogeneous loss of 1p, homogeneous loss of 14q, and the
      presence of any of the examined chromosomal aberrations (P < 0.05). The presence
      of aberrations also influenced meningioma regrowth after subtotal resection. The
      ratio of choline to glutamate correlated with histopathological subtype (P <
      0.05). The ratio of glutamine to glutamate, and the ratio of glycine to total
      glutamine and glutamate, and creatine correlated with recurrence. Alanine was
      decreased in meningiomas with chromosomal aberrations in tumors that recurred.
      CONCLUSION: Distinct molecular genetic and biochemical alterations differentiated
      clinically-aggressive Grade I meningiomas from clinically-benign Grade I
      meningiomas.

PMID- 18091282
TI  - Investigation of radiofrequency-induced temperature elevation of aneurysm clips
      in a 3.0-tesla magnetic resonance environment.
AB  - OBJECTIVE: Burn injuries associated with excessive heating of medical metallic
      devices have been reported, but a definite mechanism for magnetic resonance
      imaging-induced heating remains unresolved. The aim of this study is to evaluate
      temperature elevation of metallic wires, aneurysm clips, and clips attached to
      metallic wires under 3.0-T magnetic resonance imaging. METHODS: The temperature
      of the metallic wires, the aneurysm clips, and the clips attached to the metallic
      wires was measured with a fiber optic thermometer sensor system. RESULTS:
      Although the specific absorption rate was less than that observed during standard
      use, the temperature rapidly increased in the metallic wire. Furthermore,
      temperature elevation was observed when the clips were attached to metallic
      wires. On the other hand, not all clips showed obvious temperature elevation when
      they were placed alone in a 3.0-T magnetic resonance imaging environment.
      CONCLUSION: Aneurysm clips, when placed alone in a 3.0-T magnetic resonance
      imaging environment, are confirmed to be safe during temperature elevation.

PMID- 18091283
TI  - Matrix metalloproteinase inhibition attenuates brain edema in an in vivo model of
      surgically-induced brain injury.
AB  - OBJECTIVE: Neurosurgical procedures can result in brain injury by various means,
      including direct trauma, hemorrhage, retractor stretch, and electrocautery. This
      surgically-induced brain injury (SBI) can cause postoperative complications such
      as brain edema after blood-brain barrier (BBB) disruption. The present study
      seeks to test a matrix metalloproteinase (MMP) inhibitor for preventing
      postoperative brain edema and BBB disruption in an in vivo model of surgically
      induced brain injury. METHODS: A rodent model of SBI was used which involves
      resection of a part of the right frontal lobe. A total of 89 Sprague-Dawley male
      rats (weight, 300-350 g) were randomly divided into four groups: 1) SBI with
      vehicle treatment (0.1% dimethyl sulfoxide), 2) SBI with single treatment of MMP
      inhibitor-1 (an inhibitor of MMP-9 and MMP-2), 3) SBI treated daily (total 3
      times) with MMP inhibitor-1, and 4) sham surgical group. Postoperative assessment
      at different time periods included evaluation of BBB permeability, brain water
      content (brain edema), neurological scoring, histology, immunohistochemistry, and
      zymography for MMP enzymatic activity. Temporal magnetic resonance imaging
      studies were also performed to assess postoperative edema. RESULTS: The results
      indicate that SBI caused increased brain water content (ipsilateral frontal lobe)
      and BBB permeability compared with sham animals. Treatment with MMP inhibitor-1
      attenuated MMP-9 and MMP-2 activity and decreased brain water content with
      preservation of the BBB. CONCLUSION: Inhibition of MMP-9 and MMP-2 attenuates
      brain edema and BBB disruption after SBI. The study suggests a potential role for
      MMP inhibition as preoperative therapy before neurosurgical procedures.

PMID- 18091284
TI  - The development of neurosurgery at the National Hospital for Neurology and
      Neurosurgery, Queen Square, London, England.
AB  - The National Hospital for Neurology and Neurosurgery, Queen Square, London is one
      of the oldest clinical neuroscience hospitals in the world. It was formed from
      the fusion of itself with the Maida Vale Hospital in 1948. More recently, in
      1996, it was incorporated into the University College London Hospitals group. It
      has had many distinguished neurosurgeons on its staff, whose history from Sir
      Victor Horsley to the present is described with particular reference to the
      development of the specialty of neurosurgery. The current neurosurgical staff and
      future developments of neurosurgery at the hospital are also elucidated.

PMID- 18091285
TI  - The seminal contributions of Johann-Christian Reil to anatomy, physiology, and
      psychiatry.
AB  - Johann-Christian Reil (1759-1813) was a prominent German physician, anatomist,
      physiologist and a professor at the Universities of Halle and Berlin. Anatomic
      features named after him include the island of Reil (insula), Beau-Reil cross
      furrows, Reil's finger, the fillet of Reil, and Reil's triangle. In 1795, he
      founded the first German journal of physiology, Archiv fur die Physiologie.
      Later, he would also be considered the founder of German psychiatry (the "German
      Pinel") and coined the term "psychiatry." In addition, he was a private
      confidante and physician to Johann Wolfgang von Goethe. Reil died in 1813 from
      typhus while treating soldiers wounded in the Battle of the Nations at Leipzig
      during the Napoleonic Wars.

PMID- 18091286
TI  - Knowledge from quality improvement activities?

PMID- 18091287
TI  - Essentials of a productive nurse work environment.
AB  - BACKGROUND: Staff nurse work environments must be improved. To do so, their
      quality must be measured. The Essential of Magnetism (EOM) tool measures eight
      characteristics of a productive and satisfying work environment identified by
      staff nurses in magnet hospitals as essential to quality patient care. The EOM
      items are based on grounded theory and are used to measure attributes of the work
      environment as functional processes. The EOMII is a revision of two of the
      subscales of the EOM. OBJECTIVES: To test the hypotheses that staff nurses in
      hospitals designated as having excellent work environments (Magnet) will score
      significantly higher on the EOMII and on two outcome indicators than will their
      counterparts in Comparison hospitals. Additional aims include establishing the
      psychometric properties of the EOMII; updating the National Magnet Hospital
      Profile; ascertaining relationships between nurse attribute, work, and contextual
      variables and the characteristics of a productive work environment; and
      investigating the relationship between the magnet structure, care processes and
      relationships and two single-item indicators, overall job satisfaction, and nurse
      assessed quality of patient care. METHODS: This was a secondary analysis of
      aggregated data from 10,514 staff nurses in 34 hospitals who completed the EOMII
      and the two outcome indicators. RESULTS: The EOMII is a valid and reliable
      measure of the quality of work environment from a staff nurse perspective. The
      hypotheses were confirmed. There are differences in essentials and outcome
      variables by (a) context-nurses in magnet hospitals report the most productive
      work environment; (b) education-master's prepared nurses report the most
      favorable environments; (c) experience-the most inexperienced and the most
      experienced report the most satisfying, productive environments; and (d) clinical
      unit-medical and surgical specialty and outpatient units report the healthiest
      work environments. DISCUSSION: The primacy of magnet designation as a contextual
      variable indicating a quality work environment was affirmed. A larger percentage
      of magnet hospitals meet the magnet profile now than in 2003. Item analysis of
      the EOMII subscales provides guidance on how to improve the unit work
      environment. Suggestions are made for additional study and research.

PMID- 18091288
TI  - Cluster analysis of elderly cardiac patients' prehospital symptomatology.
AB  - BACKGROUND: Chest pain routinely brings patients into the healthcare system, and
      elderly patients may present with more complex symptoms presaging ischemic heart
      changes than do younger patients. OBJECTIVE: To examine, using cluster analysis,
      how elderly patients experiencing an ischemic coronary heart disease cluster
      based on presenting symptoms in the week before hospitalization and how they vary
      in terms of their general physical and mental health, mood states, and quality of
      life. METHODS: Elderly (age >or=65 years), unpartnered patients (N = 247)
      admitted with ischemic coronary heart disease to one of five university medical
      centers were inducted into a clinical trial; only baseline data are reported.
      Interviews assessed cardiac symptoms, medical history, general physical and
      mental health, mood states, and quality of life. Patients were clustered
      (grouped) using squared Euclidean distances and weighted average linkage.
      Characteristics of patients were examined using analysis of variance and chi
      squared analyses. RESULTS: Three clusters (groups) were identified: (a) Classic
      Acute Coronary Syndrome (severe ischemic pain; 22%), (b) Weary (severe fatigue,
      sleep disturbance, and shortness of breath; 29%), and (c) Diffuse Symptoms (mild
      symptomatology; 49%). Post hoc tests revealed that the Weary group was more
      likely to have a history of heart failure; they also exhibited significantly more
      psychological distress and lower quality of life than the other subgroups.
      CONCLUSION: Cluster analysis proved useful in grouping patients based on their
      symptom experience, but further research is needed to clarify the relationships
      among identified symptoms, psychological distress, and health outcomes; develop
      interventions for Weary patients; and extend the findings of this study.

PMID- 18091289
TI  - A telephone-only motivational intervention to increase physical activity in rural
      adults: a randomized controlled trial.
AB  - BACKGROUND: Both urban and rural adults are likely to be inactive, but rural
      adults have less access to exercise classes or facilities to increase physical
      activity. OBJECTIVES: To evaluate whether a telephone-only motivational
      interviewing (MI) intervention would increase daily physical activity of rural
      adults. METHODS: This randomized controlled trial enrolled 86 physically inactive
      adults living in rural communities (mean age = 58 years, range = 30-81 years) who
      stated that they were ready to increase physical activity during the next 6
      months. Participants were assigned randomly to MI intervention (n = 43) or
      control (n = 43) groups. The MI group participants received a pedometer and
      monthly MI telephone calls over 6 months from a counselor. Control group
      participants received an equal number of telephone calls without MI content.
      Physical activity was measured by self-report using the Community Healthy
      Activities Model Program For Seniors Physical Activity Questionnaire for Older
      Adults. Data were collected by mailed surveys and analyzed using analysis of
      variance. RESULTS: Seventy-two participants completed the study (35 in the
      intervention group and 37 in the control group). The telephone-only MI
      intervention increased self-efficacy for exercise (p = .019) but did not increase
      levels of physical activity (p = .572) compared with controls. DISCUSSION: The
      intervention increased self-efficacy for exercise but did not increase physical
      activity, possibly due to seasonal effects, the control condition, or the length
      of the MI intervention. Even so, future studies are warranted because telephone
      only MI has potential as a practical, relatively inexpensive method to provide
      health counseling to rural adults in a broad geographic area. This study produced
      an effect size on physical activity that will be useful to guide future studies.

PMID- 18091290
TI  - Efficacy of nurse case-managed intervention for latent tuberculosis among
      homeless subsamples.
AB  - BACKGROUND: The efficacy of a nurse case-managed intervention was evaluated in
      subsamples of participants with one of the following characteristics: female
      gender, African American ethnicity, recruited from a homeless shelter, a history
      of military service, lifetime injection drug use, daily alcohol and drug use,
      poor physical health, and a history of poor mental health. OBJECTIVE: To
      determine whether a validated nurse case-managed intervention with incentives and
      tracking would improve adherence to latent tuberculosis infection treatment in
      subsamples of homeless persons with characteristics previously identified in the
      literature as predictive of nonadherence. METHODS: A prospective 2-group site
      randomized design was conducted with 520 homeless adults residing in 12 homeless
      shelters and residential recovery sites in the Skid Row region of Los Angeles
      from 1998 to 2003. RESULTS: Daily drug users, participants with a history of
      injection drug use, daily alcohol users, and persons who were not of African
      American race or ethnicity had particularly poor completion rates, even in the
      nurse case-managed intervention program (48%, 55%, 54%, and 50%, respectively).
      However, the intervention achieved a 91% completion rate for homeless shelter
      residents and significantly improved latent tuberculosis infection treatment
      adherence in 9 of 12 subgroups tested (odds ratios = 2.51-10.41), including daily
      alcohol and drug users, when potential confounders were controlled using logistic
      regression analysis. DISCUSSION: Nurse case management with incentives appears to
      be a good foundation for increasing adherence to 6-month isoniazid treatment in a
      variety of homeless subgroups and, in particular, for sheltered homeless
      populations. However, additional social-structural and environmental strategies
      are needed to address those at greatest risk of nonadherence.

PMID- 18091291
TI  - Construct validity of the Korean Women's Abuse Intolerance Scale.
AB  - BACKGROUND: Domestic violence against married women has persisted throughout
      Korean history. However, very little empirical research has been conducted in
      Korea about domestic violence, its causes, or women's responses. OBJECTIVE: To
      develop and test psychometrically the Korean Women's Abuse Intolerance Scale
      (KWAIS) to measure women's propensity or desire to leave abusive husbands in
      Korea. METHODS: The first phase of the investigation involved qualitative
      research to explore the themes of women's responses to domestic violence and the
      development of the instrument. The second phase was a preliminary study conducted
      to examine women's responses to domestic violence. In the third phase, construct
      validity of the scale was established, using a sample of 184 married women living
      in Korea. RESULTS: The KWAIS adequately supported the underlying theory of
      women's responses to domestic violence, demonstrating strong content validity,
      high internal consistency (Cronbach's alpha of .98), and criterion-related
      validity evidenced by significant correlations that supported hypotheses among
      abuse intolerance and abuse (r = .69), traditional family ideology (r = -.78),
      marital satisfaction (r = -.85), attitude toward power ascription (r = .63), and
      collectivism (r = -.88). Factor analysis yielded a four-factor structure,
      explaining 78.4% of the common variance. Factor loadings ranged from .65 to .93.
      DISCUSSION: The findings for the psychometric properties of the KWAIS established
      its potential as a research instrument in measuring Korean women's propensity or
      desire to leave abusive husbands. Future studies need to focus on determining the
      predictive validity of the KWAIS and evaluating cross-cultural differences in
      women's propensity or desire to leave abusive husbands.

PMID- 18091292
TI  - Cytokine comparisons between women with breast cancer and women with a negative
      breast biopsy.
AB  - BACKGROUND: Understanding the biological milieu associated with disease states
      has important implications for biobehavioral research. Cytokines, signaling
      molecules that mediate and regulate immunity, inflammation, and hematopoiesis,
      are an important component of the biological milieu associated with breast
      cancer. Cytokines have been used as biomarkers in research for prognosis and have
      been associated with symptoms and adverse outcomes in multiple conditions,
      including breast cancer. To date, however, the examination of cytokine patterns
      has been limited by traditional laboratory methods. Advances in proteomic
      technology now permit the characterization of a broader array of cytokines in a
      single specimen. Because cytokines operate in integrated networks, a more
      complete understanding will be gained as multiple cytokines can be examined for
      patterns of response that may be associated with symptoms and prognosis.
      OBJECTIVES: To use proteomic technology (a) to examine whether there was a
      difference in cytokine levels and patterns in women with breast cancer compared
      with controls, (b) to define and compare the receiver operator characteristic
      curves for standard cytokine classifications, and (c) to identify the best
      fitting empirical model of cytokines to distinguish groups of women found to have
      breast cancer from those with negative biopsies. METHODS: The cytokine levels of
      35 women who had been diagnosed recently with breast cancer were compared with 24
      women with a suspicious breast mass who were found subsequently to have a
      negative breast biopsy. Multiplex bead array assays permitted the simultaneous
      measure of multiple markers in a small volume of serum. Nonparametric procedures
      were used to determine differences in the median values and the distributions for
      each cytokine. The receiver operator characteristic curves were defined to
      identify patterns of cytokines. RESULTS: There were significantly higher systemic
      cytokine values in women with cancer in comparison with those in women without
      cancer for all cytokines measured, with the exception of granulocyte colony
      stimulating factor and interferon-gamma. The only significant associations found
      between cytokines and age or race were increased levels of interleukin-8 (r =
      .53) and macrophage inflammatory protein-1 beta (r = .45) with increased age in
      women with a negative biopsy. Three cytokines (granulocyte colony-stimulating
      factor, interleukin-6, and interleukin-17) distinguished between the breast
      cancer and no-cancer groups with an exceptionally high areas under the curve
      (0.981; SE = 0.017). DISCUSSION: Levels of cytokines and their patterns were
      markedly different in women with breast cancer as compared with those in women
      who did not have breast cancer. Results from this study highlight the need for
      further research to examine the levels and patterns of cytokines that may serve
      as biomarkers in clinical research. Innovations in proteomic technology have
      implications for expanding biobehavioral research.

PMID- 18091293
TI  - Videorecording in clinical research: mapping the ethical terrain.
AB  - BACKGROUND: Videography is used increasingly for data collection in clinical
      research; however, addressing related ethical issues and obtaining institutional
      review board approval to use videography are often significant and daunting
      challenges for investigators. Guidelines and specific strategies are extremely
      limited in the literature. To protect the interests of videorecorded patient and
      clinician research participants, several ethical issues deserve thoughtful
      consideration and planning: informed consent, confidentiality and privacy, and
      participant burden and safety. APPROACH: The Study of Patient-Nurse Effectiveness
      with Assisted Communication Strategies is used to illustrate how these ethical
      issues can be managed in a clinical trial. Excerpts from informed consent
      documents are included, and special attention is given to the critical care
      environment, vulnerable patient populations, and clinicians as participants.
      RESULTS: Ethical issues related to the use of videography for patient-oriented
      research in the acute care hospital setting are clarified, and specific examples
      of how these issues can be addressed are provided. DISCUSSION: Ethical issues
      related to using videorecording in acute care research can be adequately
      addressed through existing universal human subjects protection strategies when
      the precise nature of the ethical issues is defined clearly.

PMID- 18091294
TI  - Multidimensional scaling: a brief overview.
AB  - BACKGROUND: Multidimensional scaling (MDS) is an exploratory technique used to
      identify unrecognized dimensions affecting behavior. Using MDS reduces large
      amounts of data to relatively simple, easy-to-visualize structures that reveal
      important relationships in an economical way and provides general solutions to
      many problems in perception, emotion, and cognition, where the stimuli are too
      complex to be quantified by other means. OBJECTIVE: To provide a basic
      introduction to MDS for the nonmathematician, in particular, the spatial distance
      model, which maps objects as points in a multidimensional space. METHODS: This
      introductory article is focused on the spatial distance model, which is used to
      map objects as points in a multidimensional space. A brief overview of MDS is
      provided, the procedure is outlined with examples, and nursing implications are
      discussed. RESULTS: Individual and aggregate analyses and individual differences
      scaling results are presented. DISCUSSION: Using MDS is ideal for the study of
      such complicated issues as a patient's perception of cancer pain, breathlessness
      in individuals with chronic obstructive pulmonary disease, and the assessment of
      vulnerable populations where social desirability bias is an issue.

PMID- 18091295
TI  - Symposium in tribute to a nursing leader: Ada Sue Hinshaw.

PMID- 18091296
TI  - Nursing practice and work environment issues in the 21st century: a leadership
      challenge.
AB  - A leadership conference titled "Have Patient Safety and the Workforce Shortage
      Created the Perfect Storm?" was held in honor of Dr. Ada Sue Hinshaw, who was
      ending her tenure as dean of the University of Michigan School of Nursing. A
      morning panel on the preferred future for practice featured plenary speaker Dr.
      Linda Burnes Bolton and participating panelists Dr. Sanjay Saint, Dr. Jane
      Barnsteiner, and Dr. Joanne Disch. Each speaker presented a unique yet
      complementary perspective, with several common themes permeating the morning's
      presentations. For example, all of the speakers mentioned how important
      interprofessional collaboration is to promoting patient safety. The themes can be
      categorized broadly as nursing practice and work environment issues, with
      subthemes of interprofessional communication and collaboration, systems solutions
      to patient safety problems, and future directions in nursing education. A
      synopsis of comments made during the morning practice panel and empirical support
      for the themes and subthemes identified by panelists are provided in this
      article.

PMID- 18091297
TI  - The perfect storm: patient safety and nursing shortages within the context of
      health policy and evidence-based practice.
AB  - Dr. Ada Sue Hinshaw stepped down from her deanship at the University of Michigan
      School of Nursing, leading to a conference in honor of her legacy held in May
      2006. The topic of the conference highlighted Dr. Hinshaw's accomplishments in
      the area of health policy and patient safety. The proceedings of the afternoon
      included four presentations. The common themes of the presentations incorporated
      the importance of public policy for patient safety, the need for health systems
      reforms, and the use of appropriate evidence-based practice to advance the
      nursing sciences. These and other perspectives of the speakers are discussed
      within the context of the broad categories of system reform, contributions from
      nursing research, and health policy focus. Finally, recommendations were given
      for the preferred future.

PMID- 18091298
TI  - Charting the course for patient safety: closing comments.
AB  - Several themes related to patient safety and the nursing workforce have been
      discussed by conference presenters. These themes include the surveillance role of
      nursing, the growing impact of healthcare services on patients and families, and
      the ongoing challenges related to nursing education. The interdisciplinary nature
      of healthcare and the implications that this has for collaboration in education
      and practice are examined also. All these themes have critical implications for
      research and leadership development. Until these pressing themes are addressed,
      the issues raised in the presentations today will remain unresolved.

PMID- 18091299
TI  - Navigating the perfect storm: balancing a culture of safety with workforce
      challenges.
AB  - Balancing the development of cultures of safety with nursing workforce challenges
      is similar to navigating the perfect storm. The perfect storm is characterized as
      a tempest of extreme intensity that happens rarely, maybe once every 100 years,
      as a result of multiple factors that end in a situation worse than people have
      ever seen. Such a storm is currently evident when attempting to ensure patient
      safety while being confronted with a shortage of nurses and nursing faculty
      unlike any other shortage experienced in over a number of decades. Based on
      research, the threats to patient safety from healthcare system and health
      professional errors have become of paramount concern. The prevention of such
      errors is the focus of healthcare organizations as they create cultures of
      safety. A major aspect of cultures of safety is nurses with their many roles in
      caring for patients and families, especially the constant surveillance they
      provide, which often prevents complications and deaths secondary to failure to
      rescue. However, providing such surveillance requires adequate numbers of well
      prepared nurses in attendance. The perfect storm is created because of the
      existence of a steadily worsening shortage of nurses and nursing faculty.
      Multiple factors have converged to develop and sustain such a shortage. A
      blueprint for healthcare organizations is proposed, with examples of numerous
      innovative strategies that are being developed and studied for handling the major
      challenges posed by this perfect storm.

PMID- 18091300
TI  - Elevated intraocular pressure and myopic shift linked to topiramate use.
AB  - PURPOSE: The purpose of this report is to describe acute myopia as an ocular
      adverse reaction to topiramate (Topamax, Ortho-McNeil, Raritan, NJ) and discuss
      the importance of recognizing this syndrome. METHODS: Retrospective case report
      and brief review of the literature. RESULTS: A 27-year-old female patient
      developed decreased vision in both eyes due to acute myopia 2 weeks of after
      initiating therapy with topiramate. Emergency department evaluation revealed
      visual acuities of 20/400 right eye and 20/200 left eye. Intraocular pressures
      were 33 mm Hg right eye and 26 mm Hg left eye. The anterior chambers were
      shallow. Retinal striae were present in the maculae. The patient stated no
      previous need for optical correction. However, after initiating treatment with
      topiramate, she refracted to approximately -5.00 D bilaterally. Ultrasound
      testing revealed that the patient had suprachoroidal effusions in both eyes. The
      symptoms and clinical findings resolved completely with discontinuation of
      topiramate, administration of topical atropine 1% and prednisolone acetate 1%.
      CONCLUSIONS: An acute myopic shift may be the presenting sign of an idiosyncratic
      drug reaction that can include secondary bilateral angle closure glaucoma. This
      condition can occur in patients who do not have a history of anterior chamber
      abnormalities. Recognizing this condition and discontinuing the use of the
      causative drug may prevent angle closure and associated vision loss.

PMID- 18091301
TI  - Spectral optical coherence tomography in video-rate and 3D imaging of contact
      lens wear.
AB  - PURPOSE: To present the applicability of spectral optical coherence tomography
      (SOCT) for video-rate and three-dimensional imaging of a contact lens on the eye
      surface. METHODS: The SOCT prototype instrument constructed at Nicolaus
      Copernicus University (Torun, Poland) is based on Fourier domain detection, which
      enables high sensitivity (96 dB) and increases the speed of imaging 60 times
      compared with conventional optical coherence tomography techniques. Consequently,
      video-rate imaging and three-dimensional reconstructions can be achieved,
      preserving the high quality of the image. The instrument operates under clinical
      conditions in the Ophthalmology Department (Collegium Medicum Nicolaus Copernicus
      University, Bydgoszcz, Poland). A total of three eyes fitted with different
      contact lenses were examined with the aid of the instrument. Before SOCT
      measurements, slit lamp examinations were performed. RESULTS: Data, which are
      representative for each imaging mode, are presented. The instrument provided high
      resolution (4 microm axial x 10 microm transverse) tomograms with an acquisition
      time of 40 micros per A-scan. Video-rate imaging allowed the simultaneous
      quantitative evaluation of the movement of the contact lens and assessment of the
      fitting relationship between the lens and the ocular surface. Three-dimensional
      scanning protocols further improved lens visualization and fit evaluation.
      CONCLUSIONS: SOCT allows video-rate and three-dimensional cross-sectional imaging
      of the eye fitted with a contact lens. The analysis of both imaging modes
      suggests the future applicability of this technology to the contact lens field.

PMID- 18091305
TI  - Oxygen and glucose distribution after intracorneal lens implantation.
AB  - PURPOSE: Insertion of an implant in the cornea to achieve corneal multifocality
      has been suggested as a solution for presbyopia. However, unresolved issues
      related to nutrient transport need to be resolved. Our aim was to find the best
      lens position and influence lens transport properties in order to optimize
      nutrient supply to corneal cells. METHOD: An axisymmetric corneal model was built
      to simulate the nutrient transport in the cornea. Oxygen and glucose
      concentrations were calculated for normal cornea and intracorneal lens wearing
      conditions. The simulation considers the different tissue layers (epithelium,
      stroma, and endothelium) as well as layer and solute concentration dependent
      consumption. RESULTS: The minimum oxygen tension in the cornea was found to be
      higher when the lens was placed at 3/4 of the corneal thickness. Moreover, in
      this position, the influence of the inlay diffusivity was smaller than at more
      anterior or posterior placements. The diffusivity of the inlay affects the way
      nutrients will be transported through the cornea. The threshold where glucose may
      diffuse through or around the implant was found to be 1/100th of the stromal
      diffusivity. CONCLUSIONS: Computational methods are especially attractive to
      study nutrient transport in the cornea due to the difficulties associated with in
      vivo or in vitro measurements. The exact parameters that dictate the corneal
      metabolism are not known. However, the combined analysis of oxygen and glucose
      distribution is valuable in order to predict the complex physiological changes
      that arise under intracorneal lens implantation.

PMID- 18091306
TI  - Grading contact lens complications under time constraints.
AB  - PURPOSE: To investigate the effect of observation time on the precision of
      grading the severity of contact lens complications. METHODS: Twenty-five
      optometry students used the Efron Grading Scales for Contact Lens Complications
      to grade the severity of one image of each of the 16 forms of anterior eye
      pathology depicted in the Efron scales. This procedure was repeated for
      observation times of 0.1, 2, and 60 s. RESULTS: Overall, significantly greater
      grading precision (smaller standard deviation of mean grades) was demonstrated
      for longer observation times (p < 0.004); however, certain complications appear
      to require longer observation times for precise grading. There was a highly
      significant dependence of the mean grade on image (p < 0.0001), observation time
      (p < 0.0001), and observation time-image interaction (p < 0.0001). CONCLUSIONS:
      Overall, a brief viewing time of a few seconds is typically all that is required
      for precise grading of ocular complications of contact lens wear. Some forms of
      pathology are more complex and may require more time to grade precisely.

PMID- 18091307
TI  - Normal aging and the perception of curvature shapes.
AB  - PURPOSE: The present study assessed whether different curve geometries involve
      different perceptual processing levels and whether these perceptual requirements
      can interact with the normal aging process. METHODS: Amplitude thresholds for
      three different curve types were assessed for young and older observers using
      2AFC psychophysical methods. The stimuli were individually adjusted for
      visibility. The three stimulus types evaluated represented a bell shape, a
      quadratic, and a compressed arc function. RESULTS: As predicted, the geometry
      influenced the perception of curvature where the compressed arc was most
      difficult to perceive followed by the quadratic and bell-shaped curves. Moreover,
      older observers showed relatively higher thresholds for the quadratic and
      compressed arc shapes, while they had similar thresholds to the younger observers
      for the bell-shaped function. CONCLUSIONS: In general, the data support the
      notion that aging affects the processing of curvature requiring the integration
      of oriented receptors. This is in accordance with studies that have found reduced
      orientation selectivity of cortical neurons in senescent animals. Our findings
      suggest that older observers would have more difficulties with form
      discrimination tasks where curvature is an inherent component of the image and
      also predict age-related differences in perceiving ophthalmic lens-induced
      distortions.

PMID- 18091308
TI  - The evaluation of two new computer-based tests for measurement of Aniseikonia.
AB  - PURPOSE: To evaluate the accuracy and repeatability of size lens induced
      aniseikonia measurement with the Aniseikonia Inspector Version 1 and a newer
      customized version of the Aniseikonia Inspector, Version 2. METHODS: Aniseikonia
      was measured on 27 subjects with both versions of the Aniseikonia Inspector in
      normal room illumination. Measurements of induced aniseikonia were made using
      size lenses in a randomized order. Twenty-five subjects were further tested in
      the dark using target sizes of equal visual angle for both tests. Repeatability
      of the intrinsic aniseikonia measurement was assessed on five subjects using
      randomized testing order for instrument and light and dark measurements. RESULTS:
      In normal illumination, the mean slopes for plots of induced aniseikonia vs. size
      lens magnification for Version 1 were 0.883 and 0.838 for the vertical and
      horizontal meridians, respectively. For Version 2, the corresponding slopes were
      1.162 and 1.043. In the dark and using targets of the same size for both tests,
      the slopes for Version 1 were 1.038 in the vertical meridian and 0.866 in the
      horizontal meridian whereas for Version 2, the slopes were 1.195 in the vertical
      meridian and 1.127 in the horizontal meridian. The amount of underestimation or
      overestimation within any given testing condition showed considerable
      intersubject variation. Version 1 was more repeatable than 2, particularly in the
      vertical meridian. CONCLUSIONS: On average, the most accurate and repeatable
      measurement of aniseikonia was found with Version 1 in the vertical meridian in
      the dark. Measurement of aniseikonia in the horizontal meridian appears to be
      less reliable. Version 2 overestimates size lens-induced aniseikonia under all
      testing conditions. Intersubject variation in slopes of induced aniseikonia vs.
      size lens magnification should be further addressed.

PMID- 18091310
TI  - Abstracts from the 19th Annual Southern Region Burn Conference.

PMID- 18091309
TI  - Binocular photophobia after surgical treatment in intermittent exotropia.
AB  - PURPOSE: This study examined the rate of binocular photophobia in intermittent
      exotropia patients before surgical correction, and the factors affecting this
      rate. The study also investigated the factors affecting postsurgical
      disappearance of binocular photophobia. METHODS: The study involved 162 basic
      type intermittent exotropia patients who underwent surgical correction between
      March 2001 and January 2006. The study did not include patients with entropion,
      congenital cataract, or retinal abnormalities. Parents of the patients were
      questioned to determine which patients had monocular eye closure in bright light
      and which had disappeared after bilateral lateral rectus recession. Data was
      analyzed to determine the factors affecting monocular eye closure before surgery
      and disappearance after surgery. RESULTS: Of 162 patients, 96 patients had
      binocular photophobia (60.2%). Photophobia was found to be associated with an
      angle of exodeviation at distance >25 Prism Diopter (Delta) (p = 0.02), and
      stereoacuity worse than 60 s (p = 0.02). We defined satisfactory surgical outcome
      as a deviation of <10 Delta. Of the 81 patients with satisfactory outcomes, 46
      showed disappearance of binocular photophobia (53.5%). No factor was found to be
      associated with loss of binocular photophobia. CONCLUSION: The angle of
      strabismus and stereoacuity were found to affect the occurrence of binocular
      photophobia. Successful surgery treated binocular photophobia in 53.5% of
      patients. Regardless of the surgical result, clinicians should educate patients
      in terms of the possibility of persistence of postsurgical photophobia.

PMID- 18091311
TI  - Malignant adenomyoepithelial tumor of the breast: multi-immunolabeling technique
      and detailed immunophenotypic study.
AB  - Biphasic ductal and myoepithelial lesions of the breast are uncommon. A majority
      of these rare lesions behave in a benign fashion. Malignancy is rare, and
      preferentially involves the epithelial component. Malignancy in both epithelial
      and myoepithelial components is even rarer. We report such a case, employing the
      use of a range of cytokeratins and myoepithelial markers to delineate the extent
      of each component. In addition, we apply the relatively novel technique of multi
      immunolabeling combined with Adobe Photoshop imaging to highlight the different
      components of the neoplasm on the same tissue section. These ancillary tests can
      provide much needed information about the contribution of epithelial or
      myoepithelial components to malignant tumors, hence providing the gateway to
      further study into their histogenesis and natural history.

PMID- 18091312
TI  - Desmoplastic small round cell tumor (DSRCT) with ovarian involvement in 2 young
      women.
AB  - We report 2 cases of desmoplastic small round cell tumor (DSRCT) involving the
      ovaries in young women. The first patient presented with symptoms of acute
      appendicitis and the second patient presented with a mass in the lower abdomen
      and slightly elevated CA-125 level. In both patients, the tumor was widely
      metastatic at presentation. The ovarian involvement was unilateral in the first
      patient and bilateral in the second with tumor size ranging from 9 to 11 cm.
      Morphology, immunohistochemistry, and molecular cytogenetics were consistent with
      DSRCT. Despite tumor debulking and multiple chemotherapy regimens, the first
      patient died at 20 months after initial diagnosis and the second is still
      undergoing chemotherapy at 7 months after initial presentation. To gain
      additional insight on DSRCT with ovarian involvement, the literature was reviewed
      and summarized.

PMID- 18091313
TI  - A simplified, sensitive immunohistochemical detection system employing signal
      amplification based on fluorescyl-tyramide/antifluorescein antibody reaction: its
      application to pathologic testing and research.
AB  - The catalyzed signal amplification (CSA) technique, based on the peroxidase
      mediated deposition of haptenized tyramide and also known as tyramide signal
      amplification and catalyzed reportor deposition systems, is widely accepted as a
      signal amplification method for immunohistochemistry and in situ hybridization.
      In this study, we examined the applicability of a new simplified CSA system
      employing fluorescyl-tyramide (FT) to pathologic testing and research with
      formalin-fixed, paraffin-embedded tissues. By using the FT, instead of biotinyl
      tyramide (BT) that is commonly employed in the CSA system with chromogen,
      nonspecific staining caused by endogenous biotin was completely avoided. The FT
      CSA system loaded on the automated immunostaining equipment also allowed for more
      reproducible detection in short times. When applied to cyclin D1 immunostaining
      that is important in differentiation among small B-cell lymphomas, the system was
      useful in demonstrating its protein expression in mantle cell lymphomas
      considered negative or equivocally positive for cyclin D1 in a conventional
      immunodetection. In immunohistochemistry for phosphorylated proteins and murine
      hematologic markers that often require higher sensitivity than conventional
      methods, the FT-CSA system provided desirable staining results with intense
      signal amplification. Our results indicate that the simplified CSA system
      employing the FT can be useful in enlarging the target range for routine
      immunohistochemistry due to its high applicability.

PMID- 18091314
TI  - A microwave technique for double indirect immunostaining of human brain tissue
      cultures with mouse monoclonal antibodies.
AB  - The use of 2 monoclonal antibodies during double immunohistochemistry would
      enable the use of a greater variety of antibody combinations. Here, we
      demonstrate a simple, cost effective method of double indirect immunostaining of
      cultured cells using primary antibodies from the same species. This method uses
      microwaving of cell samples immediately after the application of the first
      secondary antibody, and significantly reduces the level of nonspecific staining.
      This technique does not elute the antibodies, nor raise the sample temperature
      above 37 degrees C.

PMID- 18091315
TI  - Immunohistochemical staining of plastic (methyl-methacrylate)-embedded bone
      marrow biopsies applying the biotin-free tyramide signal amplification system.
AB  - Immunohistochemistry of trephine bone marrow biopsies plays a prominent role in
      diagnostic assessment of a broad spectrum of non-neoplastic and neoplastic
      hematologic and metastatic diseases. We tested the quality of immunohistochemical
      stainings in sections of methyl-methacrylate-embedded core biopsies prepared
      according to the so-called Hannover-method of cold polymerization using the novel
      biotin-free tyramide signal amplification system in comparison to the alkaline
      phosphatase-conjugated "EnVision" method. Examining a large panel of
      immunohistochemical markers, the amplification system proved to be a highly
      sensitive technique substantially superior to the EnVision-AP method in reliably
      detecting the antigenic determinants of the target cells and referred to the
      intensity of immunoprecipitations.

PMID- 18091316
TI  - Cytoplasmic fine granular expression of 8-hydroxydeoxyguanosine reflects early
      mitochondrial oxidative DNA damage in nonalcoholic fatty liver disease.
AB  - To clarify the possible role of oxidative stress in hepatocytes in nonalcoholic
      fatty liver disease, the hepatic expression of 8-hydroxydeoxyguanosine (8-OHdG),
      a good marker of oxidative DNA damage, was immunohistochemically investigated in
      nonalcoholic steatohepatitis (NASH) and steatosis. In double immunostaining, the
      cytoplasmic fine granular 8-OHdG expression was considered to reflect 8-OHdG
      positive mitochondrial DNA affecting oxidation stress. In steatosis, 4 of 8 cases
      showed cytoplasmic 8-OHdG, 1 case showed nuclear 8-OHdG and 1 case showed both
      cytoplasmic and nuclear 8-OHdG. In contrast, 8-OHdG expression was more
      frequently detected in NASH (12 of 13 cases, 92%). Immunoreactivity for 8-OHdG
      was observed only in the cytoplasm with a fine granular pattern (1 of 13 cases,
      8%), only in the nucleus (6 of 13 cases, 46%), and in both the cytoplasm and the
      nucleus (5 of 13 cases, 38%). Megamitochondria also exhibited 8-OHdG intensely.
      We indicate that 8-OHdG expression in the cytoplasm with a fine granular pattern
      reflects oxidative damage to the mitochondrial DNA of hepatocytes in both NASH
      and steatosis. We propose herein that the evaluation of cytoplasmic 8-OHdG may be
      a sensitive diagnostic marker of early nonalcoholic fatty liver disease events.

PMID- 18091317
TI  - SMAC-expression in denervated human skeletal muscle as a potential inhibitor of
      coexpressed inhibitor-of-apoptosis proteins.
AB  - In multinucleated skeletal muscle fibers, apoptotic muscle fiber loss is mediated
      by a consecutive disassembly of single fiber segments. During this period of
      time, proapoptotic and antiapoptotic factors compete for promotion or inhibition
      of apoptotic fiber degradation. In 16 patients with a neurogenic muscular
      atrophy, we studied the immunohistochemical expression of the inhibitor-of
      apoptosis proteins (IAP) survivin, cIAP1, and XIAP and also of second
      mitochondria-derived activator of caspase (SMAC), which is released during
      apoptosis and binds to IAPs to prevent them from inhibiting caspases. Although
      normal control muscle fibers show no expression of SMAC and IAPs, there was a
      distinct sarcoplasmic expression of SMAC (12.0%+/-3.5%), survivin (10.2%+/-4.0%),
      cIAP1 (9.0%+/-3.1%), and XIAP (11.0%+/-4.6%) in varying numbers of muscle fibers
      in neurogenic muscular atrophy. Coexpression of SMAC and IAPs varied. Some
      denervated muscle fibers displayed up-regulation of either SMAC or IAPs. Other
      groups of atrophic muscle fibers showed coexpression of SMAC and IAPs. All
      factors were exclusively up-regulated in atrophic muscle fibers. These findings
      indicate that IAPs may inhibit apoptotic degradation of denervated muscle fibers.
      However, IAPs are finally insufficient to counterbalance and prevent muscle fiber
      apoptosis, as up-regulated expression of SMAC can antagonize this antiapoptotic
      potential and promote apoptotic muscle fiber disassembly and loss. The interplay
      between IAPs and SMAC may represent a threshold for muscle fiber-degrading
      caspase activities. If this bears a therapeutic potential in the prevention of
      loss of denervated muscle fibers, it remains highly speculative.

PMID- 18091318
TI  - MGMT immunohistochemical expression and promoter methylation in human
      glioblastoma.
AB  - O6-methylguanine-DNA methyltransferase (MGMT) expression has been recently
      proposed as a useful prognostic and/or predictive marker in glioblastoma patients
      receiving adjuvant therapy after the surgery. We studied samples from 50 patients
      with histologically confirmed GBM to evaluate MGMT expression by
      immunohistochemistry and its relation to promoter methylation status. Genomic DNA
      was extracted from scrapings of formalin-fixed, paraffin-embedded tissue
      corresponding to hematoxylin and eosin sections. Using the mouse monoclonal
      antibody MT3.1, MGMT expression was assessed and scored in tumor cells:
      (1=negative or limited to <10% positive tumor cells, 2=10% to 50%, 3=>50%).
      Methylation-specific polymerase chain reaction was performed after bisulfite
      treatment. Assessment of MGMT expression in neoplastic tissue required careful
      scrutiny because of its expression in a variety of non-neoplastic cells. MGMT
      expression was present in tumor cells with a score of 1, 2, and 3, respectively
      in 36 (72%), 13 (26%), and 1 (2%) cases. Methylation-specific polymerase chain
      reaction yielded interpretable results in 39 cases (78%). MGMT promoter
      methylation was detected in 15 cases (38.5%), whereas 24 (61.5%) were
      unmethylated. Among the methylated samples, 14 (of 15) had a score of 1, and 1
      had a score of 3 by immunohistochemistry. Of the 24 unmethylated samples, 18 had
      a score of 1, and 6 of 2. There was no significant correlation between MGMT
      expression and methylation, and no significant survival difference was observed
      between patients whose tumors were negative versus positive for MGMT protein by
      immunohistochemistry. This study underscores some of the difficulties in applying
      immunohistochemistry to assess MGMT expression.

PMID- 18091319
TI  - Her-2/neu expression in salivary duct carcinoma: an immunohistochemical and
      chromogenic in situ hybridization study.
AB  - Salivary duct carcinoma (SDC) shares significant morphologic and immunophenotypic
      overlap with ductal carcinoma of the breast, including HER-2/neu expression.
      Previous studies have detected HER-2/neu at the protein level in SDCs; however,
      no study, to date, has assayed whether this expression is related to gene
      amplification detected by chromogenic in situ hybridization (CISH). Formalin
      fixed, paraffin-embedded tissue sections from 12 previously diagnosed SDCs were
      evaluated by immunohistochemistry (IHC) and CISH for HER-2/neu status. Result
      concordance was seen in all 12 cases. A total of 4 SDCs were positive by IHC; all
      4 cases showed amplification with CISH. The remaining 8 cases were negative by
      IHC and showed no gene amplification with CISH. SDCs in this study show HER-2/neu
      overexpression on both the protein and gene levels in approximately 30% of cases.
      These findings suggest a role may exist for Herceptin (trastuzumab) based therapy
      in some SDC patients.

PMID- 18091320
TI  - Tenascin and fibronectin expression in carcinoma ex pleomorphic adenoma.
AB  - This study was conducted to analyze the participation of tenascin and
      fibronectin, components of the extracellular matrix, in different types of
      carcinoma ex pleomorphic adenoma (CXPA). Seventeen cases of CXPA, classified
      according to the presence of epithelial and myoepithelial cells and the degree of
      invasion-intracapsular, minimally, and frankly invasive carcinoma-were
      immunohistochemically labeled for tenascin and fibronectin. Normal salivary gland
      included in the specimens showed tenascin only around the excretory duct, and
      fibronectin slightly expressed all over the stroma of the gland. In reminiscent
      pleomorphic adenoma, tenascin and fibronectin were observed around tubular
      structures and in the stroma. Both tenascin and fibronectin were expressed in all
      the CXPA studied. In areas of in situ carcinoma of the intracapsular type, the
      expression of these extracellular matrix proteins was enhanced compared with
      areas of residual pleomorphic adenoma. In intracapsular and minimally invasive
      types of CXPA, some areas of the tumor border presented tenascin and no
      fibronectin, pattern that may represent the real invasive front. In frankly
      invasive CXPA type with only epithelial component, fibronectin was strongly
      observed in a fibrillar network pattern, and tenascin was only focal. In frankly
      invasive type with myoepithelial component, tenascin staining was very strong and
      diffuse. This study showed different patterns of expression of tenascin and
      fibronectin along the process of tumorigenesis and tumor progression in CXPA, a
      fact that might play a role in invasion properties of these tumors.

PMID- 18091321
TI  - Pancreatic endocrine tumors-c-erb B2 (Her-2/neu), bcl-2, and p-53
      immunohistochemical testing and their value in assessing prognosis.
AB  - INTRODUCTION: In an attempt to identify better prognostic factors, and the
      genetic basis of pancreatic endocrine tumors (PETs), we evaluated
      immunohistochemical reactivity for c-erb B2 (Her-2/neu), bcl-2, and p53. METHODS
      AND MATERIALS: Two pathologists reviewed hematoxylin and eosin slides and
      immunohistochemical stains from 28 cases, 27 tumors and 1 nesidioblastosis. Using
      WHO criteria for malignancy (presence of local or lymphovascular invasion and/or
      metastases), cases were divided into malignant (20 cases) and benign or uncertain
      (8 cases). Nuclear staining in >1% of cells was considered positive for p53 and
      bcl-2, whereas membranous staining was considered positive for c-erb B2 (Her
      2/neu). RESULTS: All cases were nonimmunoreactive with anti-c-erb B2 (Her-2/neu),
      but focal granular or diffuse cytoplasmic staining was seen in occasional
      neoplasms. One malignant PET showed reactivity with anti-p53, whereas all others
      were negative. bcl-2 reactivity was identified in 15/28 cases: 9/20 malignant
      PETs and 6/8 others were positive. CONCLUSIONS: c-erb B2 (Her-2/neu) and p53 are
      not useful prognostic factors in PET. c-erb B2 (Her-2/neu) staining must be
      carefully evaluated to avoid the misinterpretation of artifactual/background
      staining. bcl-2 is occasionally expressed in PET, but the significance of this
      finding is still to be determined.

PMID- 18091322
TI  - Immunohistochemical localization of interleukin-6 in human pancreatitis.
AB  - The aim of the study was to identify immunohistochemically the localization of
      interleukin (IL)-6 in normal pancreas and in chronic pancreatitis (CP). Samples
      of tissues of normal pancreas (n=5) and CP (n=16), were verified
      histopathologically and then IL-6 was localized by immunohistochemical staining
      using the monoclonal antihuman IL-6 antibody and test LSAB2-HRP to visualize IL
      6/Ab complexes. In slices of the pancreas, derived from patients with CP, a much
      stronger immunohistochemical reaction was noticed as compared with controls
      specimens. IL-6 was localized in exocrine, islet cells and ducts cells of the
      pancreas. Interestingly, this cytokine was detected in cytoplasm and very close
      to nucleus. Moreover, in cases of CP with inflammatory infiltration, there were a
      markedly stronger IL-6 expression, than that observed in specimens without
      infiltrate. In conclusion, the results presented herein clearly demonstrated a
      moderate and strong expression of IL-6 in exocrine and endocrine cells of
      patients with CP. These observations provide further support for the existence of
      local immune-pancreatic interactions.

PMID- 18091323
TI  - Comparison of immunohistochemical markers in the differential diagnosis of
      adrenocortical tumors: immunohistochemical analysis of adrenocortical tumors.
AB  - Most adrenocortical tumors (ACTs) can be diagnosed directly by a combination of
      morphologic features and clinical findings. However, sometimes it may be
      difficult to distinguish ACTs from other neoplasms such as pheochromocytomas and
      some metastatic tumors, particularly for small biopsy specimens because they may
      be morphologically similar. Expression of calretinin has recently been suggested
      as a valuable immunomarker for the differential diagnosis between ACTs and other
      tumors; however, its diagnostic value is still under debate. To determine the
      diagnostic value of calretinin in Chinese patients with adrenocortical and non
      ACTs, we employed both polyclonal and monoclonal anticalretinin to characterize
      the expression of calretinin in adrenal tissues and compared its expression with
      that of inhibin alpha, Melan-A, cytokeratin, or CD99 by immunohistochemistry in
      tissue microarrays and standard tissue sections of 414 specimens. Our results
      revealed that calretinin was expressed by adrenocortical cells, but not by the
      other cells tested and the percentage of calretinin-positive ACTs reached 99%
      when stained with polyclonal antibodies, which was higher than that with
      monoclonal anticalretinin (91.3%), anti-Melan-A (90.3%), antiinhibin alpha
      (81.6%). In addition, our results also revealed that ACTs were stained by
      cytokeratin (AE1/AE3) with variable degrees (58.7%). Furthermore, unlike anti
      Melan-A that stained all metastatic malignant melanoma, anticalretinin did not
      recognize other tested tumors. Therefore, immunohistologic staining with
      polyclonal anticalretinin is more sensitive than other antibodies tested for the
      diagnosis of ACTs. However, monoclonal anticalretinin appeared to be more
      specific. Importantly, our data suggested that the fried-egg-like staining
      pattern, but not the mere cytoplasmic staining, was characteristic of
      anticalretinin staining in adrenocortical tissues. Notably, a few anticalretinin
      negative-ACTs were stained by other immunomarkers that we tested. Thus, the
      combinational characterization of calretinin (either by polyclonal or monoclonal
      antibody), inhibin alpha, and Melan-A expression is of great significance in the
      differential diagnosis of ACTs.

PMID- 18091324
TI  - NQO1 expression in pancreatic cancer and its potential use as a biomarker.
AB  - Pancreatic ductal adenocarcinoma (PDA) is rarely curable due to
      regional/metastatic spread at diagnosis. Identification of molecular markers may
      enhance diagnosis and early detection of PDA. The 2-electron reductase,
      NAD(P)H:quinone oxidoreductase (NQO1) has been found to be overexpressed in many
      solid tumors including PDA, and may be a useful clinically relevant diagnostic
      marker of malignancy. For this study, we used 37 surgical resection cases: 24
      PDAs and 13 benign pancreatic tissue specimens. An additional 16 specimens from
      pancreatic endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) were
      included as a pilot series. NQO1 was detected by avidin-biotin based
      immunohistochemical and immunocytochemical methods. Both staining intensity and
      proportion of NQO1 positive tumor cells were scored. Moderate to strong (2 to 3+)
      staining for NQO1 was detected in 22/24 (92%) surgically resected PDAs, 9/9
      (100%) EUS-FNAs with malignant diagnoses, one cytologically atypical but not
      diagnostic for malignancy EUS-FNA, and 1/6 (17%) EUS-FNAs initially diagnosed as
      negative for malignancy. Subsequent histologic assessment confirmed malignancy in
      all 9 cytologically positive EUS-FNAs and in the atypical case. The NQO1 positive
      case initially diagnosed as negative for malignancy showed no evidence of
      carcinoma on subsequent tissue biopsy. NQO1 staining was also observed in some
      benign ducts/cells; however, correlation of NQO1 expression with cellular
      morphology assessment minimizes the risk of false positive diagnosis. NQO1 is
      consistently overexpressed in PDA. Although NQO1 is observed in some benign
      tissue components, this marker may be a clinically useful diagnostic adjunct for
      detection of PDA, independent of tumor grade/stage.

PMID- 18091325
TI  - Maspin and Mutant p53 expression in malignant melanoma and carcinoma: use of
      tissue microarray.
AB  - Maspin (mammary serine protease inhibitor), a member of the serpin family, has
      been shown to inhibit angiogenesis, tumor invasion, and metastasis. Previous
      studies suggest a p53-dependent regulatory pathway of maspin protein expression.
      Its loss correlates with progression of disease in both breast and prostate
      cancer. We studied the in vivo correlation of maspin expression with p53 mutation
      in malignant melanoma (MM) with and without use of tissue microarray (TMA).
      Seventy-seven MMs were immunostained on individual slides for maspin and p53
      expression. Results were validated in 1 slide for each marker on a TMA system
      (TARP-2) with 498 tissue cores (0.6-mm diameter) from MM, other tumors, and
      normal tissue. The relationship between maspin and p53 in MM and carcinomas of
      other sites (breast, ovary, colon, lung, and prostate) was delineated using
      Pearson chi analysis. The inverse relationship between maspin and p53 expression
      predicted by hypothesized p53 regulation of maspin transcription, or any other
      correlation between these 2 markers, is not demonstrated in MM cases, using
      either classic individual slide (P=0.20) or TMA (P=0.85) methods when cutoffs for
      both markers are set at 10% or greater of cells staining. Even when cutoffs are
      altered with respect to either intensity or percentage of cells staining, no
      relationship is demonstrated between these markers, with either TMA or the
      conventional slide method. TMA immunostaining also showed no such relationship in
      carcinomas of the various other sites sampled-including breast and prostate,
      where previous studies have suggested a linkage. Despite published experimental
      evidence linking these 2 markers, this study failed to demonstrate correlation
      between maspin loss and p53 expression in MM using both individual slides and
      TMA, or in TMA of other carcinomas. Use of TMA is a quick, easy, and inexpensive
      method of immunohistochemical analysis of large numbers of cases, both to
      validate results obtained from individual slides and to assess specificity in a
      variety of neoplasms. However, heterogeneity and minimal tumor may lead to
      variable results.

PMID- 18091326
TI  - Maspin and p53 protein expression in gastric adenocarcinoma and its clinical
      applications.
AB  - OBJECTIVES: To investigate the role of maspin and p53 expression in the
      progression of gastric cancer, and its value as a prognostic indicator. MATERIALS
      AND METHODS: The expression of maspin and p53 in 152 cases of gastric cancer was
      detected by immunohistochemistry and compared with the clinicopathologic tumor
      parameters. The relationship between maspin and p53 expression was also analyzed
      in the gastric cancers. RESULTS: The positive expression rates for maspin and p53
      in the cancers were 71.7% (109 of 152 cases) and 56.6% (86 of 152 cases),
      respectively. Two patterns of immunostaining for maspin were seen in the maspin
      positive gastric cancer cases: cytoplasm-only staining (67.0%, 73 of 109 cases)
      and staining of both cytoplasm and nucleus (33.0%, 36 of 109 cases). Maspin
      expression showed a negative association with histologic grade, depth of
      invasion, metastasis, and TNM stage (all P<0.05). p53 expression showed an
      association with node metastasis, and TNM stage (both P<0.05). Maspin expression
      was negatively correlated with p53 expression (P<0.001, r=-0.291). In univariate
      log-rank analysis, loss of maspin expression, histologic grade, distant
      metastasis, and TNM stage were associated with patient survival. Interestingly,
      patients with nuclear and cytoplasmic maspin expression survived longer than
      those with only cytoplasmic expression. However, in multivariate analysis TNM
      stage and regional node metastasis were the only independent prognostic factors.
      CONCLUSIONS: Maspin expression might be an important factor in tumor progression
      and patient prognosis, but is not an independent prognostic factor. Maspin
      expression is inversely correlated with mutant p53 expression in gastric cancer,
      which suggests that maspin expression is regulated by the p53 pathway.

PMID- 18091327
TI  - Androgen receptor coactivator ARA70alpha and ARA70beta isoform-specific
      antibodies: new tools for studies of expression and immunohistochemical
      localization.
AB  - ARA70 is a coactivator of androgen receptor (AR), a ligand-dependent
      transcription factor that plays an important role in prostate cancer. There are 2
      variants of ARA70, the full length 70 kd ARA70alpha isoform and the internally
      spliced 35 kd ARA70beta isoform. Recent studies have suggested different
      expression and roles of the 2 isoforms in several endocrine malignancies,
      including prostate, breast, and ovarian cancers. To study the roles of these
      isoforms in cancers, we produced isoform-specific polyclonal antibodies. The anti
      ARA70alpha antibody was raised in rabbits against 326 amino acid peptide
      corresponding to the internal deletion missing from ARA70beta (ARA70id), whereas
      the anti-ARA70beta antibody was raised against 18 amino acid polypeptide spanning
      the splice junction, with Gln-Gln motif unique to ARA70beta. The antisera were
      affinity purified on CNBr-activated sepharose 4B, and their specificity tested
      against bacterially expressed, Ni-column-purified ARA70alpha, ARA70beta, and
      ARA70id. The anti-ARA70alpha antibody recognized ARA70alpha and ARA70id, but not
      ARA70beta. The anti-ARA70beta antibody was specific to ARA70beta and did not
      cross-react with ARA70alpha or ARA70id. We then used these antibodies to detect
      ARA70 isoforms in crude extracts made of prostate cancer cell lines and performed
      immunohistochemical localization of these proteins in prostate tissues. ARA70beta
      localized to the cytosol, whereas ARA70alpha was found in the nucleus, supporting
      the notion of their dissimilar functions.

PMID- 18091328
TI  - Expression of tissue factor in prostate cancer correlates with malignant
      phenotype.
AB  - Tissue factor (TF), apart from its established role in hemostasis, has been
      implicated in promoting angiogenesis and metastasis in a wide array of tumors
      including prostate cancer. Expression of TF was evaluated in freshly-resected
      prostate specimens obtained from patients with localized (n=9) and androgen
      ablated (n=6) disease using real-time reverse transcription-polymerase chain
      reaction and Western blot analysis. TF was detected in all specimens in both
      stages of the disease. We further analyzed for correlations between TF expression
      and those of several angiogenic growth factors and their receptors. TF RNA
      expression correlated significantly with expression of vascular endothelial
      growth factor-A in these specimens (s=0.621, P=0.013). Eighty-one prostate
      specimens from patients with benign prostatic hyperplasia (n=27), localized
      prostate cancer (ES, n=32), and advanced disease (n=22) were also evaluated using
      immunohistochemistry and findings were correlated with clinical parameters. TF
      expression was detected on epithelial cells of the malignant glands. Furthermore,
      its expression levels correlated significantly with Gleason score (s=0.58,
      P=0.0001) and with the stage of the disease (s=0.441, P=0.0001) in these
      specimens. These data support the role of TF in angiogenesis and disease
      progression.

PMID- 18091329
TI  - Persistent allergic rhinitis includes different pathophysiologic types.
AB  - BACKGROUND: Allergy rhinitis is typically classified as seasonal allergy rhinitis
      (SAR) and perennial allergy rhinitis (PAR). More recently, the Allergic Rhinitis
      and its Impact on Asthma document proposed the intermittent (ITR) and persistent
      forms (PER). However, it has been previously reported that each single allergen
      may induce different clinical and pathophysiologic features. OBJECTIVE: The aim
      of the study was to test the hypothesis that the type of causal allergen might
      characterize pathophysiologic differences in a cohort of patients with PER.
      METHODS: Three hundred nineteen patients, sailors of the Italian Navy, with
      moderate-severe PER were prospectively and consecutively evaluated with clinical
      evaluation, skin prick test, rhinomanometry, and nasal decongestion test.
      RESULTS: Patients with pollen allergy showed significantly more severe symptoms,
      lower nasal airflow, and higher response to decongestion test than patients with
      allergy to perennial allergens (P < .0001). CONCLUSION: This study provides
      evidence that patients with PER may show different pathophysiologic patterns
      depending on the type of causal allergen.

PMID- 18091330
TI  - Cochleovestibular anomalies in children with cholesteatoma.
AB  - OBJECTIVE: To describe the cochleovestibular apparatus on computed tomography
      (CT) imaging in patients with cholesteatoma. We asked whether cochleovestibular
      anomalies coexist in individuals with cholesteatoma. STUDY DESIGN: Randomized,
      controlled, prospective measurement. METHODS: A database search yielded 145
      children with cholesteatoma: 31 met inclusion criteria by not having
      sensorineural hearing loss, not having an associated syndrome, and having
      digitally stored temporal bone CT imaging available. Prospective measurement of
      31 individuals (62 ears) with unilateral cholesteatoma and 32 normally hearing
      nonsyndromic controls (64 ears) was performed by a neuroradiologist blinded to
      the study objective. Twenty-six temporal bone aspects on axial imaging were
      evaluated (16 measurement, 10 calculated from measurement). RESULTS: The
      cholesteatoma group had a larger endolymphatic fossa and vestibular aqueduct, and
      there was a trend for the lateral semicircular canal vestibule to be smaller as
      compared with controls. Subgroup analysis revealed a gradient in prevalence of
      these findings being most common in the congenital cholesteatoma group,
      intermediate in the acquired cholesteatoma group, and least common in controls.
      There were no differences in measurements between ears with cholesteatoma and
      contralateral disease-free temporal bones. CONCLUSIONS: Children with
      cholesteatoma have abnormal vestibular anatomy. The gradient in prevalence of
      these findings may suggest a relationship between congenital and acquired
      cholesteatoma. These may include a generalized temporal bone anomaly that
      predisposes to cholesteatoma formation, or a third variable such as genetic
      mutation may predispose to both anomalous cochleovestibular formation and
      cholesteatoma.

PMID- 18091332
TI  - 3 Tesla delayed contrast magnetic resonance imaging evaluation of Meniere's
      disease.
AB  - OBJECTIVE: To determine whether 3 Tesla (T) magnetic resonance imaging (MRI) with
      delayed contrast imaging has sufficient anatomic resolution to image the
      intracochlear fluid spaces (i.e., the scala tympani, scala media, and scala
      vestibuli) of the inner ear and identify endolymphatic hydrops in vivo. STUDY
      DESIGN: Four normal subjects underwent 3T MRI scanning after the administration
      of gadodiamide intravenous (IV) contrast. MRI region of interest signal intensity
      was used to determine the diffusion of gadodiamide into the perilymphatic fluid
      spaces over time. Seven subjects with unilateral Meniere's disease underwent 3T
      MRI 4 hours after administration of gadodiamide IV contrast agent. RESULTS: All
      four normal subjects demonstrated perilymphatic enhancement by 4 hours
      postinjection. Loss of definition of the membranous cochlea was noted in five of
      the seven subjects with Meniere's disease. Precise definition of the scala media
      could not be achieved with this imaging protocol. CONCLUSION: Delayed contrast
      imaging of the inner ear with 3T MRI revealed in vivo changes of the membranous
      labyrinth consistent with unilateral Meniere's disease.

PMID- 18091331
TI  - Quantification of myosin heavy chain RNA in human laryngeal muscles: differential
      expression in the vertical and horizontal posterior cricoarytenoid and
      thyroarytenoid.
AB  - BACKGROUND: Human laryngeal muscles are composed of fibers that express type I,
      IIA, and IIX myosin heavy chains (MyHC), but the presence and quantity of
      atypical myosins such as perinatal, extraocular, IIB, and alpha (cardiac) remain
      in question. These characteristics have been determined by biochemical or
      immunohistologic tissue sampling but with no complementary evidence of gene
      expression at the molecular level. The distribution of myosin, the main motor
      protein, in relation to structure-function relationships in this specialized
      muscle group will be important for understanding laryngeal function in both
      health and disease. OBJECTIVES: We determined the quantity of MyHC genes
      expressed in human posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscle
      using real-time quantitative reverse-transcriptase polymerase chain reaction in a
      large number of samples taken from laryngectomy subjects. The PCA muscle was
      divided into vertical (V) and horizontal (H) portions for analysis. RESULTS AND
      CONCLUSIONS: No extraocular or IIB myosin gene message is present in PCA or TA,
      but IIB is expressed in human extraocular muscle. Low but detectable amounts of
      perinatal and alpha gene message are present in both of the intrinsic laryngeal
      muscles. In H- and V-PCA, MyHC gene amounts were beta greater than IIA greater
      than IIX, but amounts of fast myosin RNA were greater in V-PCA. In TA, the order
      was beta greater than IIX greater than IIA. The profiles of RNA determined here
      indicate that, in humans, neither PCA nor TA intrinsic laryngeal muscles express
      unique very fast-contracting MyHCs but instead may rely on differential synthesis
      and use of beta, IIA, and IIX isoforms to perform their specialized contractile
      functions.

PMID- 18091333
TI  - Outcomes studies of epiglottic and base of tongue prolapse in children.
AB  - OBJECTIVES: The purpose of this study was to compare previously reported flexible
      fiberoptic laryngoscopy (FFL) findings of a grading system for children with
      epiglottic and base of tongue (EBT) prolapse with findings at follow-up FFL.
      Surgical outcomes and tracheotomy decannulation are also reported. STUDY DESIGN:
      : Retrospective medical record review. METHODS: Fourteen children with EBT
      prolapse had transnasal FFL in the supine position on at least two occasions.
      Findings were graded for initial versus most recent FFL. The previously published
      EBT prolapse grading system was reapplied. Mean age was 8.7 years at the last
      evaluation. Mean interval between initial and most recent FFL was 1.9 years.
      RESULTS: At follow-up FFL, six (43%) children had the same grade of EBT prolapse,
      five (36%) had a milder grade, and three (21%) had a more severe grade. Five
      (36%) children were decannulated, and nine (64%) children remain tracheotomy
      dependant. Of nine children who had surgery, four (44%) were decannulated. Eight
      (89%) of nine children who were not decannulated have a history of developmental
      delay (P < .03). Twelve (86%) children had gastroesophageal reflux disease, and
      six (43%) had abnormal swallowing function. CONCLUSIONS: The grading system was
      successfully reapplied to compare initial with follow-up findings in a cohort of
      children with EBT prolapse. Gastroesophageal reflux disease and swallowing
      dysfunction are common in this population. Judicious surgery may have some
      efficacy for EBT prolapse in selected patients. Many children with EBT prolapse
      still require tracheotomy, especially those with developmental delay.

PMID- 18091334
TI  - Long-term results of a phase III randomized trial of postoperative radiotherapy
      with or without carboplatin in patients with high-risk head and neck cancer.
AB  - BACKGROUND: The role of postoperative radiotherapy and carboplatin in squamous
      cell carcinoma of the head and neck (SCCHN) has not been established. METHODS:
      Patients with macroscopically resected stage III/IV SCCHN with high-risk
      pathologic features (> or =3 lymph nodes, extracapsular extension, perineural or
      angiolymphatic invasion, or involved margins) were randomized to receive
      postoperative radiotherapy alone (arm A) or the same radiotherapy plus
      carboplatin 100 mg/m intravenously once weekly during radiation (arm B). The
      primary endpoint was 2-year disease-free survival. RESULTS: Seventy-six patients
      were randomized, of whom 72 were eligible and analyzable (36 in each arm). The
      study was prematurely closed because of slow accrual. With a median follow-up of
      5.3 years, the disease-free survival at 2 and 5 years was 71% and 53% in arm B
      versus 58% (P = .27) and 49% (P = .72) in arm A. The overall survival at 2 and 5
      years was 74% and 47% in arm B versus 51% (P = .04) and 41% (P = .61) in arm A.
      Serious toxicities were infrequent in both arms. CONCLUSIONS: We could not
      demonstrate a benefit with the addition of carboplatin to postoperative
      radiotherapy, possibly because of insufficient sample size.

PMID- 18091335
TI  - Tympanic membrane collagen fibers: a key to high-frequency sound conduction.
AB  - OBJECTIVE: To investigate the significance of tympanic membrane collagen fiber
      layers in high frequency sound transmission. STUDY DESIGN: Human cadaver temporal
      bone study. METHODS: Laser Doppler vibrometry was used to measure stapes
      footplate movement in response to acoustic stimulation. The tympanic membrane was
      altered by creating a series of slits and applying paper patches to isolate the
      effects of specifically oriented collagen fibers. Three groups of membrane
      alterations were evaluated: 1) circumferentially oriented slits involving each
      quadrant to primarily disrupt radial fibers, made sequentially within superior
      anterior, inferior-anterior, inferior-posterior, and superior-posterior
      quadrants; 2) the same slits made in the reverse order; and 3) radially oriented
      slits from the umbo to the annulus to primarily disrupt circumferential fibers.
      For each group, measurements of the middle-ear cavity pressure, ear canal
      pressure, and stapes velocity were made each time the tympanic membrane was
      altered. RESULTS: Regardless of the order in which the circumferentially oriented
      slits were made, there was a consistent decrease in stapes velocity above 4 kHz
      for the third and fourth cuts compared to the control. The mean decrease in the
      range of 4 to 12.5 kHz was 11 dB for the third patched slit and 14 dB for the
      fourth patched slit (P < .01). Radially oriented slits appear to produce smaller
      effects. CONCLUSIONS: Radial collagen fibers in the tympanic membrane play an
      important role in the conduction of sound above 4 kHz.

PMID- 18091337
TI  - Organ preserving transoral laser microsurgery for cancer of the hypopharynx.
AB  - OBJECTIVE: To assess the feasibility of transoral laser microsurgery (TLM) in the
      treatment of hypopharyngeal cancer, with a special focus on piriform sinus
      carcinomas, and to report the oncologic and functional outcomes. STUDY DESIGN:
      Prospective case-series study at a single institute, an academic tertiary
      referral center. METHODS: A total of 172 patients with previously untreated
      squamous cell carcinoma of the hypopharynx were eligible for this study (1986
      2003). The piriform sinus was the most common localization (n = 150). Patients
      with simultaneous second primaries, distant metastases, or N3 neck disease and
      cancers of the category pT4b were excluded. Fifteen percent of the patients had
      stages I and II (according to guidelines from the Union Internationale Contre le
      Cancer 2002/American Joint Commission on Cancer, 2002), and 85% had stages III
      and IVa. The median follow-up period was 45 months. All patients (n = 172) were
      treated by TLM, mainly by selective neck dissection (93%) and/or postoperative
      radiotherapy (52%). Overall survival, recurrence-free survival, organ
      preservation, and local control were analyzed as end points. Rate of
      tracheotomies, postoperative complications, and swallowing function (feeding tube
      dependency) were also analyzed. RESULTS: : Five-year Kaplan-Meier local control
      was 84% for pT1; 70% for pT2; 75% for pT3; and 57% for pT4a. Five-year Kaplan
      Meier recurrence-free survival was 73% for stages I and II, 59% for stage III,
      and 47% for stage IVa. The whole group of 172 hypopharyngeal cancer patients was
      analyzed, with an additional special focus on the homogenous group of piriform
      sinus carcinomas (n = 150). CONCLUSIONS: Our data support the conclusion that TLM
      is a valid option to standard radical surgery or standard conservation treatment.
      Oncologic and functional results compare favorably, while morbidity and
      complication rates tend to be lower.

PMID- 18091336
TI  - Cigarette smoke activates NF kappa B and induces Muc5b expression in mouse middle
      ear cells.
AB  - OBJECTIVES: Cigarette smoke exposure is a significant risk factor in the
      development of otitis media (OM). Nuclear factor kappa B (NF-kappa B) is a
      ubiquitous transcription factor known to mediate cigarette smoke effects on gene
      regulation in multiple cell types. The MUC5B mucin gene contains several putative
      NF-kappa B sites in its promoter and is the predominant mucin expressed in human
      OM. We hypothesized that in vitro stimulation of a recently developed model
      system, murine middle ear epithelial cells (MEEC), with cigarette smoke
      condensate (CSC) activates NF-kappa B and subsequently induces Muc5b gene
      expression. METHODS: Luciferase reporter assays, electromobility shift assays
      (EMSA), and quantitative microplate transcription factor assays (TFA) were
      performed to evaluate NF-kappaB activation with CSC in immortalized murine MEEC
      (mMEEC). Reverse transcriptase polymerase chain reaction (RT-PCR) assays and
      quantitative real time RT-PCR were performed to determine whether time course CSC
      stimulation upregulates Muc5b mRNA levels in differentiated mMEEC. Luciferase
      reporter assays were performed to determine whether CSC activates the Muc5b
      promoter. RESULTS: Reporter assays, EMSA, and TFA demonstrated three- to five
      fold dose-dependent activation of NF-kappa B with CSC in mMEEC. CSC stimulation
      likewise increased Muc5b mRNA abundance and induced reporter activity 1.8- to 4.8
      fold in plasmids containing -556 and -255 base pairs upstream of the Muc5b
      transcriptional start site in mMEEC. CONCLUSIONS: CSC activates NF-kappaB in
      immortalized MEEC. Furthermore, this activation correlates with CSC-induced Muc5b
      promoter activation and gene expression. Taken together, these results hint that
      much as in lung cells, the activation of mucins by cigarette smoke is mediated in
      part by NF-kappa B.

PMID- 18091338
TI  - Aerodynamic, acoustic, and vibratory comparison of arytenoid adduction and
      adduction arytenopexy.
AB  - HYPOTHESIS: Adduction arytenopexy (AP) with thyroplasty provides improved
      physiologic placement of the vocal fold and therefore provides improved acoustic,
      aerodynamic, and vibratory function as compared with arytenoid adduction (AA)
      with thyroplasty. METHODS: Five cadaveric human larynges were prepared by
      removing supraglottic tissues and fixing the nontest vocal fold medially on the
      cricoid facet with a needle in a physiologic phonating position. Each test vocal
      fold was then sequentially tested using an excised larynx phonation system, first
      with AA with silastic medialization and then converted to AP without changing the
      contralateral fold position or silastic wedge. The excised larynx setup allowed
      for simultaneous collection of data, specifically subglottic pressure (including
      measurement of phonation threshold pressure [PTP]), mean airflow, acoustic
      output, and full-frame high-speed digital video. RESULTS: Aerodynamic evaluation
      was similar for each group with similar subglottic pressure versus output curves.
      Conditions involving AP typically had PTP values that were 80% of that for
      comparable AA conditions. Acoustic evaluation revealed differences between the
      two groups. Each AA was found to be vibrating with two dominant frequencies with
      their associated harmonics. Each AP vibrated at a single dominant frequency with
      its harmonics. CONCLUSION: AP provides improved vocal outcomes by decreasing
      system noise and decreasing PTP, which may lead to a stronger glottal signal with
      decreased vocal effort.

PMID- 18091339
TI  - Caloric function after endolymphatic sac surgery.
AB  - OBJECTIVE: To evaluate the effect of endolymphatic sac surgery on vestibular
      functions using caloric testing on electronystagmography (ENG). STUDY DESIGN:
      Retrospective chart review. METHODS: The medical records of 21 adult patients
      with unilateral Meniere's disease who underwent endolymphatic sac surgery between
      1998 and 2004 were reviewed. With use of ENG, the absolute value of the caloric
      response of the operated ear (i.e., the cool + warm irrigation response) and the
      degree of reduced vestibular response (RVR) rates as indicators of caloric
      functions were compared before and after surgery. Average follow-up was 17 (6-52)
      months. RESULTS: The mean change in RVR after surgery was found to be 2.9%. In
      total, there were six (28.5%) patients who had an RVR increase more than 10%. Of
      those, there were three (14.2%) patients who demonstrated an RVR increase more
      than 20%. Only one (4.8%) patient had an RVR increase more than 30%. Total loss
      of vestibular function was not observed in any of the patients. There were three
      (14.2%) patients who exhibited a decrease of more than 10% in their RVR. In two
      (9%) patients, the contralateral ear was shown to have less vestibular function
      than the operated side on ENG postoperatively (in one case, the absolute caloric
      nystagmus response remained the same in the operated ear, and in the other case,
      the response increased on the surgical side). When we evaluated the absolute
      caloric responses of the operated ear only, we found no statistical difference
      between the pre- and postoperative values (P = .219). Early results of vertigo
      control and hearing outcomes were comparable with those in the literature.
      CONCLUSION: Endolymphatic sac surgery does not appear to be a vestibular
      destructive procedure, and it is a therapeutic alternative for patients with
      Meniere's disease who have failed medical treatment. This is important given the
      possibility of bilateral disease in some patients.

PMID- 18091340
TI  - Waist circumference and sleep disordered breathing.
AB  - OBJECTIVES/HYPOTHESIS: To explore how the different metrics of obesity,
      specifically body mass index (BMI), Mallampati, neck circumference, waist
      circumference, and waist-hip ratio, correlate with metrics of sleep disordered
      breathing (SDB), specifically the apnea/hypopnea index (AHI), and which is/are
      the most likely to predict and correlate with SDB. STUDY DESIGN AND METHODS: Four
      hundred fourteen patients presenting to the University of California San Diego
      Head and Neck Surgery Clinic for SDB had a sleep evaluation including a history
      and physical examination assessing the markers of obesity and a sleep test. Data
      comparing AHI with BMI, neck circumference, waist circumference, waist-hip ratio,
      and Mallampati were analyzed by means, standard deviations, and Pearson's
      correlations. RESULTS: The mean AHI for males was 34, and the mean AHI for
      females was 24. The mean age was 48 for both sexes. The mean waist circumference
      for males was 104 cm (41 inches) and for females 99 cm (39 inches). In males and
      females, waist measurement was most strongly correlated with SDB (males: r =
      0.366, P = .00; females: r = 0.445, P = .00). The mean neck circumference for
      males and females was 43 cm (17 inches) and 38 cm (15 inches) (males: r = 0.358,
      P = .00; females: r = 0.38, P = .00). The mean waist-hip ratio for males and
      females was 0.94 and 0.87 (males: r = 0.359, P = .00; females: r = 0.254, P =
      .03). The mean BMI for males and females was 31 kg/m2 (males: r = 0.325, P = .00;
      females: r = 0.40, P = .00), and the mean Mallampati for males and females was
      2.84 and 2.92 (males: r = 0.176, P = .012; females: r = 0.149, P = .16). A linear
      regression demonstrated that waist and neck circumference were better correlates
      of SDB than BMI. CONCLUSION: Obesity correlates with SDB severity. Waist
      circumference is a better measure than BMI or neck circumference to predict SDB.
      Men and women are anthropometrically different. Even with an AHI of 5 or more,
      only half of SDB patients in this study were clinically obese. An abnormal waist
      circumference for men and women is 102 cm (40 inches) or more.

PMID- 18091341
TI  - A critical role for fibroblast growth factor-7 during early alveolar formation in
      the neonatal rat.
AB  - Mesenchymal cell-derived FGF-7 (fibroblast growth factor-7) induces proliferation
      in both epithelial and endothelial cells. We found FGF-7 to be expressed in the
      lungs of neonatal rats from birth to d 14 of age. A role for FGF-7 in early
      postnatal lung growth and alveolar formation, by an action on type II
      pneumocytes, has been excluded by the work of others. However, a role through an
      action of FGF-7 on other cell types has not been excluded. We used
      intraperitoneal injections of neutralizing antibodies on d 3, 4, and 5 of life to
      inhibit binding of FGF-7 to its receptors, and assessed alveolar formation on d 6
      of life. This intervention inhibited DNA synthesis in, and number of, alveoli
      forming secondary crests, resulting in a significantly reduced alveolar number.
      This failure of alveolar formation was associated with a reduction in the number
      of small blood vessels in the lung periphery. We conclude that FGF-7, most likely
      through its effect on the vascular bed, is required for normal early postnatal
      alveolar formation from secondary crests.

PMID- 18091342
TI  - 3'-monoiodothyronine sulfate and Triac sulfate are thyroid hormone metabolites in
      developing sheep.
AB  - We used novel 3'-monoiodothyronine sulfate (3'-T1S) and 3,3',5-triiodothyroacetic
      acid sulfate (TriacS) RIAs to characterize sulfation pathways in fetal thyroid
      hormone metabolism. 3'-T1S and TriacS levels were measured in serum samples
      obtained from fetal (n = 21, 94-145 d gestational age), newborn (NB, n = 5), and
      adult sheep (AD, n = 5) as well as from fetuses after total thyroidectomy (Tx),
      or sham-operated twin fetuses controls, conducted at gestational age 110-113 d (n
      = 5). Peak levels (expressed as ng/dL) of both 3'-T1S and TriacS occurred at 130
      d gestation. These levels in fetuses were higher than those in NB and AD. In Tx
      fetuses, there was a significant decrease in the mean serum level of 3'-T1S, but
      not TriacS. The decrease in 3'-T1S in Tx is similar to that observed for
      thyroxine sulfate (T4S) and 3,3',5'-triiodothyronine sulfate (rT3S), whereas
      TriacS levels were not altered in the hypothyroid state, similarly to 3,3',5
      triiodothyronine sulfate (T3S). These data demonstrate that 3'-T1S and TriacS are
      normal thyroid hormone metabolites in ovine serum and that TriacS is likely
      derived from T3S or from the same precursor(s) as T3S.

PMID- 18091343
TI  - Oxidative stress in fetal lambs exposed to intra-amniotic endotoxin in a
      chorioamnionitis model.
AB  - Chorioamnionitis is a risk factor for the development of bronchopulmonary
      dysplasia. Endotoxin-induced oxidative stress to the fetus in the uniquely
      hypoxic intrauterine environment has not been reported. Using a model of
      chorioamnionitis, we measured markers of pulmonary and systemic oxidant exposures
      in fetal lambs at 124 d gestation (term = 150 d) exposed to 10 mg intra-amniotic
      endotoxin 2 d (n = 6) or 7 d (n = 6) before delivery, or saline as controls (n =
      9). The 7 d endotoxin-exposed animals had 3-fold higher protein carbonyls (0.66
      +/- 0.46 versus 0.23 +/- 0.14 nmol/mg protein) and 10-fold greater
      myeloperoxidase activity (2.38 +/- 1.87 versus 0.27 +/- 0.18 nM) in the
      bronchoalveolar lavage fluid (BALF), suggestive of neutrophil-derived oxidant
      activity. However, in the lung tissue, protein carbonyls, superoxide dismutase,
      and peroxiredoxin 1 were not different between groups. The expression of
      peroxiredoxin 1 was prominent, primarily in the peri-bronchiolar epithelium.
      Notably, evidence of oxidant exposure was minimal at 2 d when BALF inflammatory
      cells, lung IL-1beta, and IL-8 were highest. Intra-amniotic endotoxin induced
      systemic oxidative stress as plasma protein carbonyl was elevated at 7 d (0.14 +/
      0.04 nmol/mg protein; p = 0.005). Surfactant protein A and B mRNAs were highest
      at 2 d, suggesting that oxidative stress did not contribute to the lung
      maturation response. A modest lung oxidative stress in chorioamnionitis could
      contribute to bronchopulmonary dysplasia.

PMID- 18091344
TI  - Elevated fatty acid ethyl esters in meconium of sheep fetuses exposed in utero to
      ethanol--a new animal model.
AB  - Specific fatty acid ethyl esters (FAEE) in meconium of newborns have been shown
      to correlate with maternal ethanol exposure. An animal model is needed to assess
      the validity of this biomarker. We hypothesized that the pregnant/fetal sheep is
      a feasible animal model for validating FAEE as a biomarker of prenatal ethanol
      exposure. Nine pregnant ewes were treated during the third trimester with
      different i.v. ethanol doses. The control group consisted of 14 pregnant ewes
      exposed to similar volumes of saline. On gestational d 133, the fetuses were
      delivered and meconium samples removed. FAEEs were quantified by gas
      chromatography-flame ionization detection. FAEEs were found in both control and
      ethanol exposed fetuses. Ethyl oleate, ethyl linoleate, and ethyl arachidonate
      levels were significantly higher in the ethanol-exposed sheep. Ethyl oleate was
      the FAEE that correlated most strongly with alcohol ingestion during pregnancy
      and had the greatest area under the curve (0.94). Using a cut-off value of 131
      ng/g ethyl oleate dry weight, sensitivity was 89% and specificity was 100%. In
      conclusion, pregnant ewes are a feasible model for validating biomarkers of
      prenatal ethanol exposure. Ethyl oleate, ethyl linoleate, and ethyl arachidonate
      may be useful biomarkers of prenatal alcohol exposure.

PMID- 18091345
TI  - Enteral feeding reduces endothelial nitric oxide synthase in the caudal
      intestinal microvasculature of preterm piglets.
AB  - The initiation of enteral feeding represents a challenge to the neonatal
      intestinal microcirculation, especially in preterms where it predisposes to
      necrotizing enterocolitis (NEC). We hypothesized that a structural microvascular
      deficiency may occur when enteral feeding is initiated in preterm piglets
      susceptible to NEC. Stereologic volume densities of a pan-endothelial marker
      (vWF), and the main vasodilator endothelial nitric oxide synthase (eNOS), were
      determined along the small intestine of 1) unfed preterm piglets, 2) piglets
      receiving total parenteral nutrition (TPN) for 2-3 d, and 3) piglets fed 2 d
      sow's colostrum (TPN+SOW) or milk formula (TPN+FOR) following TPN. In the mucosa,
      vWF-density decreased in a cranio-caudal direction. A corresponding mucosal eNOS
      gradient appeared only after initiating enteral feeding. In TPN+SOW, eNOS
      induction may lag behind the mucosal growth of the caudal region. In TPN+FOR,
      formula-related factors (i.e. bacteria, cytokines) may suppress mucosal eNOS,
      indicated by increased stress-sensitive nuclear HIF1alpha staining. The low
      mucosal endothelial eNOS density was related to the presence of NEC lesions,
      maybe via increased hypoxia-sensitivity, especially in the caudal region as
      indicated by nuclear HIF1alpha-staining. Our results suggest an insufficient
      structural adaptation of the microvasculature to enteral feeding, especially of
      mucosal eNOS, which may lead to NEC.

PMID- 18091346
TI  - Localization and control of expression of VEGF-A and the VEGFR-2 receptor in
      fetal sheep intestines.
AB  - We studied expression of vascular endothelial growth factor A (VEGF-A) and its
      main receptor, VEGFR-2, in the small intestine from five groups of fetal sheep
      (each n = 5): 1) preterm controls, 2) term controls, 3) preterm animals where the
      fetus was infused with cortisol, or 4) saline, and 5) term animals where
      adrenalectomy had been performed preterm. The main transcript expressed in fetal
      small intestine was VEGF-A165. Comparing term with preterm animals, there were
      significantly higher levels of expression of VEGF-A protein (p = 0.005). Levels
      of VEGF-A protein expression were lower in term adrenalectomized animals (p =
      0.01) and were higher in preterm animals infused with cortisol (p = 0.01),
      compared with their respective control groups. Immunohistochemistry demonstrated
      strongest expression of VEGF-A protein in the epithelial cells and lamina propria
      of the villi. Intestinal expression of mRNA encoding the VEGFR-2 receptor did not
      significantly vary with gestational age. In situ hybridization localized VEGFR-2
      to the lamina propria of the villous core and receptor autoradiography using 125I
      VEGF-A demonstrated binding in the same site. These data show that intestinal
      VEGF-A is up-regulated with advancing gestation in a glucocorticoid-dependent
      manner--novel findings consistent with a role for VEGF-A stimulated angiogenesis
      in preparing the fetal gut for birth.

PMID- 18091347
TI  - High levels of serum prostaglandin E2 in children with osteogenesis imperfecta
      are reduced by neridronate treatment.
AB  - Prostaglandin E2 (PGE2) is an activator of bone remodeling, and increase levels
      of PGE2 are found in several disorders characterized by chronic inflammation.
      Bisphosphonates are used in the treatment of osteogenesis imperfecta (OI), an
      inherited disorder characterized by bone fragility and low bone mass. We
      evaluated the serum PGE2 (ng/mL) level in 16 children affected by OI (11 with
      mild and 5 with severe forms) at basal time and during treatment with
      neridronate. The levels of PGE2 in mild and severe forms were increased at basal
      time compared with controls (13.14 +/- 4.2 versus 0.72 +/- 0.05, p < 0.01; 15.1
      +/- 1.5 versus 0.72 +/- 0.05, p < 0.01, respectively) and showed a significant
      decrease after the second (T1) cycle of treatment (mild: 4.97 +/- 5.0 versus
      13.14 +/- 4.2, p < 0.01; severe: 5.32 +/- 4.5 versus 15.1 +/- 1.5, p < 0.01) with
      a further significant decrease after the fourth (T2) cycle. The high basal PGE2
      levels in OI, a noninflammatory disorder, could be explained by stress-induced
      release mediated by inducible cyclooxygenase-2-catalyzed pathway. The reduction
      obtained by treatment with bisphosphonates could be attributed to a direct
      pharmacological effect since these drugs has been reported to modulate the
      release of proinflammatory mediators.

PMID- 18091348
TI  - Repetitive nociceptive stimuli in newborn rats do not alter the hippocampal
      neurogenesis.
AB  - The aim of this study was to evaluate the effects of acute repetitive nociceptive
      stimuli to newborn rats over neurogenesis rate in the dentate gyrus of
      hippocampus. Newborn rats were randomly distributed in three groups, according to
      the type of stimulus received from d 1 to d 7 of life four times per day: acute
      nociceptive stimuli, tactile stimuli, and none (controls). At d 21 of life, rats
      received BrdU (5-bromo-2'-deoxyuridine, a marker of cell proliferation), and on d
      28, they were killed. After brain sectioning, the tissue was processed for
      immunohistochemical identification of proliferating cells. BrdU-positive cell
      counts were performed in the granule cell layer of the dentate gyrus. Acute
      nociceptive stimulation during the first week of life was not associated to
      alterations in the weight gain among experimental groups. On examination 1 wk
      after BrdU injection, the number of BrdU-labeled cells in the dentate gyrus of
      the hippocampus was not significantly different between stimulated (painful and
      tactile stimuli) and nonstimulated animals. These results show that both types of
      stimuli used here, when applied very early in the development, do not affect the
      neurogenesis rate in the rat dentate gyrus.

PMID- 18091349
TI  - IKBKAP mRNA in peripheral blood leukocytes: a molecular marker of gene expression
      and splicing in familial dysautonomia.
AB  - The common familial dysautonomia (FD) mutation results in tissue specific mis
      splicing with reduced amount of wild-type (WT) IkappaB kinase associated protein
      gene (IKBKAP) mRNA and ELP1. ELP1 is a subunit of Elongator, formerly called the
      IkappaB kinase associated protein (IKAP) protein. We measured IKBKAP mRNA in
      peripheral blood leukocytes to determine whether FD subjects and carriers have
      characteristic levels. Estimated mean IKBKAP mRNA levels, measured by
      quantitative PCR and expressed as amount relative to the noncarrier average, were
      significantly different for the two groups when not adjusted for age and sex (p <
      0.001): FD subjects 0.23, 95% confidence interval (CI) (0.19, 0.28); carriers
      0.58, 95% CI (0.50, 0.68); or adjusted for age and sex (p < 0.001): FD subjects
      0.21, 95% CI (0.16, 0.26); carriers 0.66, 95% CI (0.55, 0.79). Comparison of
      IKBKAP mRNA levels of the 22 FD subjects and their related carriers showed a
      strong correlation, providing evidence for genetic control of splicing
      efficiency. IKBKAP mRNA levels were not higher in those subjects using
      tocotrienols or epigallocatechin gallate. Levels of IKBKAP mRNA in peripheral
      blood leukocytes can be used to assess molecular response to therapies aimed at
      enhancing exon 20 inclusion and increasing cellular levels of ELP1/IKAP.

PMID- 18091350
TI  - Understanding the susceptibility of the premature infant to necrotizing
      enterocolitis (NEC).
AB  - Necrotizing enterocolitis (NEC) is the most common life-threatening
      gastrointestinal emergency encountered in the neonatal intensive care unit.
      Despite advances in neonatal care, NEC remains a leading cause of morbidity and
      mortality among premature infants. Epidemiologic studies have identified multiple
      factors that increase an infant's risk for the development of NEC, although
      premature birth, bacterial colonization, and enteral feeding are thought to play
      central roles in disease pathogenesis. Appreciating factors that underlie the
      susceptibility of prematurely born infants to NEC is important for the
      development of new strategies aimed at the prevention and treatment of disease.
      In this review, we discuss defense mechanisms in the intestine and discuss how
      these systems may be insufficient in the prematurely born infant and thereby
      further contribute to initiation of NEC. In addition, based on a review of the
      literature, we suggest that, although numerous bacterial and viral pathogens have
      been associated with NEC, no individual organism is known to be responsible for
      disease. Finally, we comment on the possible role for probiotics in promoting
      maturation of intestinal defense mechanisms thereby attenuating or preventing the
      sequence of events that lead to NEC.

PMID- 18091351
TI  - Nephromegaly in children with Kawasaki disease: new supporting evidence for
      diagnosis and its possible mechanism.
AB  - To measure the kidney size in children with Kawasaki disease (KD) and to
      delineate the condition of nephromegaly, 20 children with KD were enrolled in our
      study. Kidney sizes were measured during acute stage in these patients. Twenty
      healthy children and 15 febrile children served as healthy controls and fever
      controls, respectively. To delineate the possible mechanism, we also evaluated
      kidney volume (KV) in 13 other patients with KD during the acute phase and after
      the recovery phase as well as 26 healthy children. Plasma hepatocyte growth
      factor (HGF) and transforming growth factor-beta1 (TGF-beta1) levels were
      determined for all children. Kidney lengths and KV in patients with KD during the
      acute phase were significantly larger than those of healthy children. There was
      no kidney enlargement in healthy controls and after the recovery phase. The ratio
      of patient plasma HGF/TGF-beta1 during the acute phase and after the recovery
      phase correlated positively with the degree of nephromegaly in all patients.
      These results confirm the presence of large kidneys in children with KD. Our data
      also suggest that an elevated HGF/TGF-beta1 ratio may be responsible for the
      transient nephromegaly in these children.

PMID- 18091352
TI  - Sildenafil reverses hypoxic pulmonary hypertension in highland and lowland
      newborn sheep.
AB  - Perinatal exposure to chronic hypoxia induces sustained hypertension and
      structural and functional changes in the pulmonary vascular bed. We hypothesized
      that highland newborn lambs (HLNB, 3600 m) have a higher pulmonary arterial
      pressure (PAP) due in part to a higher activity/expression of phosphodiesterase 5
      (PDE5). We administered sildenafil, a PDE5 inhibitor, during basal and hypoxic
      conditions in the pulmonary hypertensive HLNB and compared them to lowland
      newborn lambs (LLNB, 580 m). Additionally, we compared the vasodilator responses
      to sildenafil in isolated small pulmonary arteries and the PDE5 mRNA expression
      and evaluated the vascular remodeling by histomorphometric analysis in these
      newborn lambs. Under basal conditions, HLNB had a higher PAP and cardiac output
      compared with LLNB. Sildenafil decreased the PAP during basal conditions and
      completely prevented the PAP increase during hypoxia in both groups. HLNB showed
      a greater contractile capacity and a higher maximal dilation to sildenafil. PDE5
      mRNA expression did not show significant differences between HLNB and LLNB. The
      distal pulmonary arteries showed an increased wall thickness in HLNB. Our results
      showed that HLNB are more sensitive to sildenafil and therefore could be useful
      for treatment of pulmonary hypertension in high-altitude neonates.

PMID- 18091353
TI  - Genetic analysis of MMP gene polymorphisms in patients with Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute febrile disorder characterized by systemic
      vasculitis primarily occurring in coronary arteries. Matrix metalloproteinases
      (MMPs) have been considered to play pathophysiologic roles in the development of
      coronary artery lesions (CALs); therefore, an evaluation of the genetic
      contributions of the MMP genes to the development of CALs in KD patients would be
      beneficial for the prediction of CAL formation. We focused on the known
      functional single nucleotide polymorphisms (SNPs) in the MMP genes (MMP-2-735C>T,
      MMP-3-1612 5A/6A, MMP-9-1562C>T, MMP-12-82A>G, and MMP-13-77A>G) and performed
      the association study between these SNPs and CAL formation in KD. The study
      population consisted of 44 KD patients with CALs and 92 without CALs and 175
      healthy controls. As a result, allele and genotype frequencies of MMP-13-77A>G
      showed significant differences between KD patients with CALs and without CALs (p
      = 0.00989 and p = 0.00551, respectively). The estimated frequencies of the G-C
      haplotype in the MMP-13 gene promoter were significantly lower in KD patients
      with CALs than in those without CALs. There was no association between other MMP
      genes and CAL formation. In conclusion, the genetic evaluation by association
      study demonstrated that the MMP-13 gene, at least in part, contributed to the
      development of CALs in KD.

PMID- 18091354
TI  - Neonatal formula feeding leads to immunological alterations in an animal model of
      type 1 diabetes.
AB  - Neonatal diet may influence the development of type 1 diabetes (T1D) in
      susceptible individuals through an intestinal mucosal inflammatory response,
      resulting in loss of self-tolerance. We tested the hypothesis that formula
      feeding during the neonatal period accelerates the development of T1D in diabetes
      prone BioBreeding (BBDP) rats through regulation of CD4+CD25+ regulatory T
      lymphocytes (T(reg)) and anti-inflammatory cytokines. BBDP rat pups fed rat milk
      substitute (RMS) via a "pup-in-the cup" system were compared with mother-fed (MF)
      rats. The spleen and thymus were analyzed for Foxp3-expressing CD4+/CD25+ T
      cells. Multiplex enzyme-linked immunosorbent assays (ELISAs) were performed to
      measure cytokine-induced neutrophil chemoattractant (CINC), tumor necrosis factor
      alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, and
      IL-18. Diabetes-free survival, time of disease onset, and T(reg)/total T
      lymphocyte ratios were not different. MF pups had higher ileal CINC (p < 0.001)
      and IL-18 (p = 0.002), but no differences in the liver. There were no differences
      in ileal cytokine concentrations of 75-d-old rats, but the formula-fed rats had
      greater liver TNF-alpha (p < 0.001), IFN-gamma, and IL-4 (p < 0.01) and lower IL
      10 (p = 0.002) compared with MF animals. Formula versus maternal milk altered the
      hepatic cytokine profile at 75 d toward an inflammatory pattern but did not
      result in altered T(reg) cell frequencies or the development of T1D.

PMID- 18091355
TI  - Mutational analysis of the pro-opiomelanocortin gene in French obese children led
      to the identification of a novel deleterious heterozygous mutation located in the
      alpha-melanocyte stimulating hormone domain.
AB  - The pro-opiomelanocotin (POMC) plays a key role in body weight regulation, where
      its derived peptides mediate leptin action via the hypothalamic melanocortin 4
      receptor (MC4R). The pathogenic effects of POMC mutations have been challenged in
      obesity. Our aim was to assess the relevance of POMC mutations in a cohort of
      French obese and nonobese children. Direct sequencing of the POMC gene was
      performed in 322 obese and 363 control unrelated children. Functional studies for
      the novel Phe144Leu mutation included the response to alpha-melanocyte
      stimulating hormone (alphaMSH) and a competitive binding assay. POMC mutations
      were identified in 3.72% of obese [95% confidence interval (CI): 1.66-5.80] and
      2.20% of control (95% CI: 0.69-3.71) subjects. The novel mutation located in the
      alphaMSH region of the POMC gene (Phe144Leu) was found in one obese child and was
      transmitted by the obese father. Functional studies showed that MC4R activation
      in response to Leu144alphaMSH was almost completely abolished due to a
      dramatically altered binding of Leu144alphaMSH to MC4R. The frequency of POMC
      mutations is not significantly different between obese and control children in
      our cohort. The novel heterozygous mutation Phe144Leu leading to the absence of
      melanocortin signaling was associated with early-onset obesity suggesting its
      pathogenic role.

PMID- 18091356
TI  - A matched case control study of orthostatic intolerance in children/adolescents
      with chronic fatigue syndrome.
AB  - This study aimed to define cardiovascular and heart rate variability (HRV)
      changes following head-up tilt (HUT) in children/adolescents with chronic fatigue
      syndrome (CFS) in comparison to age- and gender-matched controls. Twenty-six
      children/adolescents with CFS (11-19 y) and controls underwent 70-degree HUT for
      a maximum of 30 min, but returned to horizontal earlier at the participant's
      request with symptoms of orthostatic intolerance (OI) that included
      lightheadedness. Using electrocardiography and beat-beat finger blood pressure, a
      positive tilt was defined as OI with 1) neurally mediated hypotension (NMH);
      bradycardia (HR <75% of baseline), and hypotension [systolic pressure (SysP)
      drops >25 mm Hg)] or 2) postural orthostatic tachycardia syndrome (POTS); HR
      increase >30 bpm, or HR >120 bpm (with/without hypotension). Thirteen CFS and
      five controls exhibited OI generating a sensitivity and specificity for HUT of
      50.0% and 80.8%, respectively. POTS without hypotension occurred in seven CFS
      subjects but no controls. POTS with hypotension and NMH occurred in both.
      Predominant sympathetic components to HRV on HUT were measured in CFS tilt
      positive subjects. In conclusion, CFS subjects were more susceptible to OI than
      controls, the cardiovascular response predominantly manifest as POTS without
      hypotension, a response unique to CFS suggesting further investigation is
      warranted with respect to the pathophysiologic mechanisms involved.

PMID- 18091357
TI  - Probabilistic brain tissue segmentation in neonatal magnetic resonance imaging.
AB  - A fully automated method has been developed for segmentation of four different
      structures in the neonatal brain: white matter (WM), central gray matter (CEGM),
      cortical gray matter (COGM), and cerebrospinal fluid (CSF). The segmentation
      algorithm is based on information from T2-weighted (T2-w) and inversion recovery
      (IR) scans. The method uses a K nearest neighbor (KNN) classification technique
      with features derived from spatial information and voxel intensities.
      Probabilistic segmentations of each tissue type were generated. By applying
      thresholds on these probability maps, binary segmentations were obtained. These
      final segmentations were evaluated by comparison with a gold standard. The
      sensitivity, specificity, and Dice similarity index (SI) were calculated for
      quantitative validation of the results. High sensitivity and specificity with
      respect to the gold standard were reached: sensitivity >0.82 and specificity >0.9
      for all tissue types. Tissue volumes were calculated from the binary and
      probabilistic segmentations. The probabilistic segmentation volumes of all tissue
      types accurately estimated the gold standard volumes. The KNN approach offers
      valuable ways for neonatal brain segmentation. The probabilistic outcomes provide
      a useful tool for accurate volume measurements. The described method is based on
      routine diagnostic magnetic resonance imaging (MRI) and is suitable for large
      population studies.

PMID- 18091358
TI  - Developmental absence of the O2 sensitivity of L-type calcium channels in preterm
      ductus arteriosus smooth muscle cells impairs O2 constriction contributing to
      patent ductus arteriosus.
AB  - Patent ductus arteriosus (PDA) complicates the hospital course of premature
      infants. Impaired oxygen (O2)-induced vasoconstriction in preterm ductus
      arteriosus (DA) contributes to PDA and results, in part, from decreased
      function/expression of O2-sensitive, voltage-gated potassium channels (Kv) in DA
      smooth muscle cells (DASMCs). This paradigm suggests that activation of the
      voltage-sensitive L-type calcium channels (CaL), which increases cytosolic
      calcium ([Ca2+]i), is a passive consequence of membrane depolarization. However,
      effective Kv gene transfer only partially matures O2 responsiveness in preterm
      DA. Thus, we hypothesized that CaL are directly O2 sensitive and that immaturity
      of CaL function in preterm DA contributes to impaired O2 constriction. We show
      that preterm rabbit DA rings have reduced O2- and 4-aminopyridine (Kv blocker)
      induced constriction. Preterm rabbit DASMCs have reduced O2-induced whole-cell
      calcium current (ICa) and [Ca2+]i. BAY K8644, a CaL activator, increased O2
      constriction, ICa, and [Ca]i in preterm DASMCs to levels seen at term but had no
      effect on human and rabbit term DA. Preterm rabbit DAs have decreased gamma and
      increased alpha subunit protein expression. We conclude that the CaL in term
      rabbit and human DASMCs is directly O2 sensitive. Functional immaturity of CaL O2
      sensitivity contributes to impaired O2 constriction in premature DA and can be
      reversed by BAY K8644.

PMID- 18091359
TI  - Fetal onset of general movements.
AB  - Perinatal qualitative assessment of general movements (GMs) is a tool to evaluate
      the integrity of the young nervous system. The aim of this investigation was to
      study the emergence of GMs. Fetal onset of GMs was studied sonographically in 18
      fetuses during the first trimester of uncomplicated in vitro fertilization (IVF)
      pregnancies in weekly assessments. The earliest motility consisting of small and
      simple sideways bending (SB) of head and/or rump starts at 7 wk, lasting about 1
      s. Between 7 and 8.5 wk, motility differentiates further into movements in which
      also one or two arms or legs become active; movements are still slow, small, and
      in one direction, but the duration increases to a few seconds. The transition
      into GMs at 9-10 wk is characterized by variation in participating body parts and
      amplitude, speed, and direction during longer periods of time. Between 9 and 13
      wk, simple and stereotyped SBs and GMs may coexist. At 9 wk, the incidence of SBs
      decreases (p = 0.01) and that of GMs increases (p = 0.006). The data suggest that
      initial simple fetal motility is generated by spinal and brainstem circuitries,
      and the emergence of complex and variable GMs denotes the onset of supraspinal
      modulation of this spinal and brainstem activity.

PMID- 18091360
TI  - Identification of cellular processes that are rapidly modulated in response to
      tracheal occlusion within mice lungs.
AB  - Lung development progresses through a process reliant on mechanical cell stretch.
      However, this process is not well defined at the molecular level. Our goal was to
      globally analyze the transcriptome of fetal mouse lungs following short periods
      of tracheal occlusion (TO) to identify cellular processes that are rapidly
      modulated in response to intraluminal stretch increase. Serial analysis of gene
      expression (SAGE) was used to examine the global transcriptomic response of mouse
      prealveolar stage lungs to in vivo TO at 1 and 3 h. SAGE results were extended by
      histo- and immunochemical examination. Based on the 97 TO-modulated transcripts
      identified, our results further point out that continuous stretch in developing
      lungs leads directly to rapid and highly specific phenotypic modifications in a
      significant proportion of pulmonary cells. We conclude that intraluminal stretch
      increase during prealveolar stage of lung development induces a critical
      transition of pulmonary cells phenotype in which there is an increase in alpha
      smooth muscle actin (alpha-SMA)-containing cells along with a relative decrease
      in lipid-containing cells.

PMID- 18091362
TI  - Phosphoglucomutase genetic polymorphism and body mass.
AB  - BACKGROUND: We have searched for a possible association of the genetic
      polymorphism of Phosphoglucomutase locus 1 (PGM1), a key enzyme in carbohydrate
      metabolism, with body mass. METHODS: Adults (n = 257) with type 2 diabetes, 74
      children referred for "obesity," and 740 consecutive healthy newborn infants were
      studied. Body mass index, body weight, birth weight, and PGM1 phenotype were
      determined. Sexes were analyzed separately. RESULTS: In type 2 diabetes, females
      carrying the PGM1*2 allele are less represented among subjects with extreme body
      mass index deviation as compared with other classes of subjects. Among children
      referred for "obesity," females carrying the PGM1*2 allele are less represented
      among children with extreme body weight deviation. Among consecutive infants, in
      both sexes the proportion of those showing a birth weight higher than the 3rd
      quartile is lower in homozygous PGM12/2 subjects than in other PGM1 phenotypes.
      CONCLUSIONS: The data suggest that during extrauterine life, females carrying the
      PGM1*2 allele are relatively protected from extreme body mass increase. During
      intrauterine life, PGM12/2 homozygotes show a tendency to low body mass increase.
      Because PGM1 enzymatic activity depends on its phosphorylation status by the
      kinase Pak1, both structural differences of the PGM1 allelic product and
      different rates of activation by Pak between sexes might be responsible for the
      pattern observed. At present, the effect of other genes near PGM1 and in linkage
      disequilibrium with it cannot be ruled out.

PMID- 18091361
TI  - Parathyroid hormone status does not influence blood and bone lead levels in
      dialysis patients.
AB  - Elevated blood lead levels, a risk factor for cardiovascular disease, have been
      reported among patients with end-stage renal disease. We evaluated whether these
      higher levels are due to release of lead from the skeleton because of uremic bone
      disease. Fifty-one African-American patients with end-stage renal disease were
      recruited from 3 Tulane University dialysis programs between January and July
      2005. An interviewer-administered questionnaire, blood specimen collection and
      109Cd-based x-ray fluorescence measurement of tibia lead occurred during a single
      study visit. Levels of serum parathyroid hormone (PTH), calcium, phosphorus, and
      albumin were abstracted from the patients' charts. The distributions of tibia and
      blood lead were similar across levels of serum PTH. Specifically, for
      participants with serum PTH <300 pg/mL and > or =300 pg/mL, median tibia lead was
      21 microg/g and 17 microg/g, respectively, and geometric mean blood lead levels
      were 6.7 microg/dL and 6.6 microg/dL, respectively (P = 0.70 and 0.87,
      respectively). After adjustment for age, gender, education, cigarette smoking,
      and dialysis vintage, natural log transformed blood lead was 0.022 lower in
      patients with serum PTH > or =300 pg/mL (P = 0.87). There were no differences in
      tibia and blood lead across levels of serum calcium, serum phosphorus, and the
      calcium phosphorus product (all P > 0.40). The high blood lead levels observed
      among dialysis patients do not appear to be the result of increased bone
      turnover. The causes of higher blood lead levels for these patients need to be
      identified and attenuated.

PMID- 18091363
TI  - The outcome of lupus nephritis in Jamaican patients.
AB  - We investigated the outcome of a cohort of black Jamaican patients with systemic
      lupus erythematosus (SLE) with nephritis. In 66 patients, 0 (0%), 15 (23%), 4
      (6%), 32 (48%), 6 (9%), and 3 (5%) had classes 1, II, III, IV, V, and VI,
      respectively. Six (9%) had interstitial nephritis. The patients were placed in 2
      groups for comparison. Group 1 (n = 36) consisted of classes III and IV and group
      2 (n = 27), classes II and V, and interstitial nephritis. The patients in group 1
      had significantly lower hemoglobin, higher mean serum creatinine, higher
      prevalence of hypertension, and chronicity scores. The duration of follow-up was
      similar between the 2 groups. The percent events free for ESRD or death at 1 year
      was 80.1% for group 1 and 77.4% for group 2; 2 years, 69.0% for group 1 and 77.4%
      group 2; 5 years, 69.0% for group 1 and 57.4% for group 2. The percent events
      free for death at 1 year was 93.4% in group 1 and 90.9% in group 2; at 2 years,
      86.7% for group 1 and 90, 9% for group 2; and at 5 years was 86.7% for group 1
      and 67.3% (29.5 to 88.0) for group 2. Sixteen patients (25.4%) developed ESRD or
      died. Prognosis was not different between the groups for ESRD or death (P = 0.22)
      or death alone (P = 0.63).

PMID- 18091364
TI  - cAMP and cGMP in human parotid saliva: relationships to taste and smell
      dysfunction, gender, and age.
AB  - Among the chemical moieties present in human parotid saliva, some, such as gustin
      or carbonic anhydrase VI, have been useful to distinguish patients with taste and
      smell dysfunction from normal subjects. To continue these studies we compared
      levels of salivary cAMP and cGMP in patients with taste and smell dysfunction
      with those in normal subjects. We were also interested in exploring physiological
      characteristics of salivary cAMP and cGMP including changes with gender and age
      because previous studies had not clearly defined these issues. To perform these
      studies parotid saliva was collected from 61 normal volunteers and 253 patients
      with taste and smell dysfunction. cAMP and cGMP were measured by a
      spectrophotometric 96 plate ELISA technique; parotid salivary protein and flow
      rate were also measured. Both cAMP and cGMP were found in saliva of normal
      subjects and patients in the detection range of the assay used. In patients mean
      concentrations of both cAMP and cGMP were lower than in normal subjects; for cAMP
      levels were lower among both men and women patients. cAMP was 7 to 10 times
      higher than cGMP in both normal subjects and patients. Concentrations of cAMP
      were consistently higher in normal women than in normal men. cAMP levels were
      generally lower and cGMP levels were generally higher than in previously reported
      studies. There was a complex pattern of change for both cAMP and cGMP with age
      with concentrations increasing to about age 50, then decreasing, then increasing
      again at age >70 years.

PMID- 18091365
TI  - Sarcoidosis associated with an elevated serum CA 125 level: description of a case
      and a review of the literature.
AB  - BACKGROUND AND AIM: CA 125 is a glycoprotein expressed by a variety of tissues of
      mesothelial origin. It has classically been associated with ovarian carcinoma. It
      has also been reported to be elevated in certain granulomatous conditions. We
      describe a patient with sarcoidosis and an elevated serum CA 125 level and review
      the medical literature on this topic. METHODS: We describe a patient with active
      sarcoidosis and an elevated serum CA 125 level at our institution. A search of
      medical databases revealed 4 additional cases of sarcoidosis associated with
      elevated serum CA 125 levels. RESULTS: All 5 patients (our patient and the 4
      found in medical databases) were female. Four of the 5 presented with abdominal
      symptoms or weight loss. Four of the 5 patients had evidence of peritoneal
      sarcoidosis. Three patients required treatment and their serum CA 125 levels
      declined. CONCLUSIONS: Peritoneal sarcoidosis may "mimic" ovarian carcinoma in
      that it may present with peritoneal or abdominal findings and an elevated serum
      CA 125 level.

PMID- 18091366
TI  - The predictive value of CRP levels on future severe renal disease in overweight
      and obese subjects without diabetes mellitus and hypertension.
AB  - BACKGROUND: Obesity and related disorders have a high prevalence all over the
      world. Increased C-reactive protein (CRP) value in obese individuals and its
      potential adverse effects have been reported. Here we have investigated the
      relationship between CRP levels and renal functions in nondiabetic,
      nonhypertensive, overweight, and obese individuals. The aim of this study was to
      evaluate the predictive value of CRP levels on future severe renal disease.
      METHODS: One hundred sixty individuals were included in the study. They were
      grouped as normal weight, overweight, and obese. Anthropometric measurements,
      renal function tests, and serum hsCRP values were obtained. Mean values were
      compared and correlation analysis was performed. RESULTS: Significant differences
      were detected between the groups according to body mass index, waist
      circumference (WC), and body fat percentage. There was a significant difference
      with respect to creatinine clearance (CC). Difference in the mean urinary albumin
      excretion (UAE) was significant between normal-weight and overweight subjects.
      There was a linear increase in serum CRP values in parallel to the increase in
      body weight; mean values were significant between groups. A positive correlation
      was detected between CC and body mass index and WC, and there were significant
      correlations between CRP and anthropometric measurements, CC and UAE.
      CONCLUSIONS: This study showed that increased CRP levels in nondiabetic,
      nonhypertensive, overweight, and obese individuals could possibly associated with
      impaired renal functions that might be originating from endothelial dysfunction.
      Determination of cutoff levels of CRP, as in cardiovascular diseases, may be
      useful for early estimation and prevention of renal diseases.

PMID- 18091367
TI  - Repeated thoracenteses affect proinflammatory cytokines, vascular endothelial
      growth factor, and fibrinolytic activity in pleural transudates.
AB  - BACKGROUND: Repeated thoracenteses is indicated in patients with refractory,
      symptomatic transudative effusions. However, their effect on cytokines and
      fibrinolytic activity in pleural transudates remains unclear. METHODS: Twenty-one
      patients with symptomatic, large amount of free-flowing transudative effusions
      caused by heart failure were studied. Thoracentesis with drainage of 500 mL of
      pleural fluid per day was done for 3 consecutive days (days 1 to 3). Pleural
      fluid characteristics, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1
      beta, IL-8, vascular endothelial growth factor (VEGF), tissue-type plasminogen
      activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1) were measured
      during each tap. Chest ultrasonography was done on day 6 to detect the fibrin
      strands in pleural effusion and the outcome of effusion was evaluated within 7
      days after repeated thoracenteses. RESULTS: Effusion levels of lactate
      dehydrogenase, neutrophils, TNF-alpha, IL-1 beta, IL-8, VEGF, and PAI-1 increased
      significantly during repeated thoracenteses. Furthermore, the values of PAI-1 and
      PAI-1/tPA obtained on days 2 and 3 were highly correlated with those of TNF
      alpha, IL-1 beta, IL-8, and VEGF. On day 6, pleural fibrins were observed on
      chest ultrasonography in 6 patients (29%, fibrinous group) but were absent in the
      remaining 15 patients (nonfibrinous group). Compared with the nonfibrinous group,
      the effusion levels of TNF-alpha, IL-1 beta, VEGF, and PAI-1 on day 2 and day 3,
      and recurrence of symptomatic effusion after repeated thoracenteses were
      significantly higher in fibrinous group. CONCLUSIONS: Repeated thoracenteses may
      induce local release of proinflammatory cytokines, VEGF and PAI-1, which may
      result in fibrin deposition and impair resolution of pleural transudates.

PMID- 18091368
TI  - Hemodialysis vascular catheter-related bacteremia.
AB  - Bacteremia in hemodialysis patients with cuffed tunneled catheters is a
      significant cause of morbidity and mortality. Native arteriovenous fistulas or
      vascular prostheses are preferred forms of vascular access, but their creation
      may not always be possible. Catheter-related bacteremia is due primarily to Gram
      positive organisms, but Gram-negative infections are of increasing importance.
      Bacteremia in patients with catheters results from luminal or extraluminal
      contamination and may be perpetuated by infected fibrin sheaths associated with
      the catheter. Bacteremic patients require antibiotic therapy and catheter
      removal. Guide wire catheter exchange is appropriate in stable patients, but
      catheter removal and later reinsertion of a new catheter is indicated for tunnel
      infection or frank sepsis. Late diagnosis or ineffective therapy predisposes to
      vascular and extravascular infectious complications. Catheter-related bacteremia
      may be minimized with appropriate sterile technique at insertion, meticulous exit
      site care, and antibiotic lock solutions. Early recognition and treatment
      minimize morbidity and mortality, but the optimal solution remains the placement
      of permanent access.

PMID- 18091369
TI  - Metabolic risk factors, endothelial dysfunction, and erectile dysfunction in men
      with diabetes.
AB  - BACKGROUND: The prevalence of men with erectile dysfunction (ED) and concomitant
      diabetes mellitus continues to increase. ED, diabetes, hypertension, and
      dyslipidemia (components of the metabolic syndrome) are associated with
      endothelial dysfunction. ED has been reported to be a marker for cardiovascular
      arterial disease. Effective treatment of ED requires recognition of the condition
      and its associated comorbidities, including endothelial dysfunction. METHODS: An
      electronic search of the literature was conducted to review information
      concerning the prevalence of ED, diabetes, metabolic syndrome, endothelial
      dysfunction, and treatment of ED. RESULTS: Phosphodiesterase type 5 (PDE5)
      inhibitors are effective vasodilating agents with a predominant effect on penile
      vasculature and are therefore first-line treatment for men with ED. These agents
      have also been demonstrated to have a beneficial effect in other vascular beds.
      PDE5 inhibitors have not been shown to have an adverse effect on cardiovascular
      morbidity or mortality or on glycemic control in men with diabetes. In addition,
      no causal association has been established between nonarteritic ischemic optic
      neuropathy and PDE5 inhibitors. CONCLUSIONS: PDE5 inhibitors have a beneficial
      effect on endothelial dysfunction and ED in men with diabetes and metabolic risk
      factors.

PMID- 18091370
TI  - Immunization for the elderly.
AB  - The morbidity and mortality of vaccine-preventable diseases among older adults
      are high. Despite the benefits of elderly vaccination, vaccination rates remain
      low and especially among some minority groups. Specific strategies for improving
      the rate of vaccination have been developed for medical offices and clinics,
      hospitals, and other health care institutions. There are vaccines that are
      recommended routinely for the elderly while other vaccines are recommended in
      certain circumstances. Knowing the indications, contraindications, and adverse
      reactions to the recommended vaccines for the elderly is very important to the
      primary care physicians.

PMID- 18091371
TI  - Ectopic ACTH syndrome associated with large-cell neuroendocrine carcinoma of the
      lung.
AB  - Although ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a well
      known paraneoplastic phenomenon, an association with large-cell neuroendocrine
      carcinoma of the lung (LCNEC) has not been reported. We describe a 63-year-old
      man with metastatic LCNEC to the left temporomandibular joint (TMJ) who presented
      with progressive muscle weakness and bilateral lower leg edema for 2 weeks. He
      did not have a typical Cushingoid appearance nor used diuretics. His newly noted
      hypertension, hypokalemia (plasma potassium (K) concentration 1.8 mEq/L) with
      renal K wasting, and metabolic alkalosis suggested a state of mineralocorticoid
      excess. His plasma renin activity and aldosterone concentrations were low, but
      cortisol and ACTH levels were extremely elevated, consistent with ACTH-dependent
      Cushing's syndrome. Nonsuppressible plasma cortisol level and normal sella
      turcica on magnetic resonance imaging pointed to EAS. A strongly positive stain
      for ACTH from the metastatic left TMJ mass supported LCNEC-related EAS. His
      hypokalemia and hypertension were controlled with spironolactone and K
      supplementation. This is the first reported case of EAS in LCNEC and should be
      kept in mind as a cause of hypokalemia in lung cancer patients.

PMID- 18091372
TI  - Resolution of MRI findings in central pontine myelinosis associated with
      hypokalemia.
AB  - We report a case of a 20-year-old African-American female, hospitalized and
      treated for hyperemesis gravidarum and hypokalemia with a normal serum sodium
      level. Two to 3 days into her hospitalization, she developed urinary
      incontinence, weakness, and pain in her lower extremities. An MRI brain scan
      showed central pontine signal alteration, leading to a diagnosis of CPM. A 4
      month follow-up MRI brain scan showed complete resolution of the central pontine
      signal, with symptomatic improvement manifested by resolution of urinary
      incontinence and increased strength. Our case describes CPM occurring secondary
      to hypokalemia, with resolution of characteristic MRI findings at follow-up. Sole
      hypokalemia-induced CPM is very rare. What makes our patient even more unique is
      the complete resolution of the central pontine lesion on follow-up MRI. The cause
      of this cannot be completely explained and warrants further study.

PMID- 18091373
TI  - Primary Sjogren syndrome complicated by autoimmune hemolytic anemia and pure red
      cell aplasia.
AB  - Patients with primary Sjogren syndrome frequently present hematologic
      abnormalities, consisting mainly of immune cytopenias. Pure red cell aplasia is a
      very rare complication of primary Sjogren syndrome. This is the first report in
      the literature describing the development of pure red cell aplasia combined with
      autoimmune hemolytic anemia in a 74-year-old woman with primary Sjogren syndrome.
      In our patient, despite administration of diverse therapeutic schemes, such as
      corticosteroids, immunomodulating agents (intravenous immune globulin),
      immunosuppressive drugs (cyclophosphamide), and novel treatment options
      (monoclonal antibody directed against the CD20 antigen), no response was
      achieved. The present case suggests that the possibility of comorbid connective
      tissue disease should be a diagnostic consideration in patients with acquired
      pure red cell aplasia and autoimmune hemolytic anemia. Although most of the
      hematologic abnormalities that occur in primary Sjogren syndrome are not
      clinically significant, serious and difficult-to-treat hematologic complications
      may also occur.

PMID- 18091374
TI  - "Rescue" bilateral adrenalectomy in paraneoplastic Cushing's syndrome with
      invasive Aspergillus fumigatus infection.
AB  - We report the case of a patient with life-threatening Aspergillosis during
      paraneoplastic Cushing's syndrome. Anticortisolic drug ketoconazole was unable to
      lower severe hypercortisolism and despite antifungal treatment available at this
      time (liposomal amphotericine B and terbinafine), Aspergillus fumigatus infection
      was uncontrolled and extensive. "Rescue" bilateral adrenalectomy was performed to
      control hypercortisolism, leading to rapid fungal infection cure. We emphasize
      surgical management of hypercortisolism to achieve rapid blunting of cortisol
      production in a such life-threatening situation.

PMID- 18091375
TI  - Rapidly propagating descending necrotizing mediastinitis as a consequence of
      intravenous drug use.
AB  - Descending necrotizing mediastinitis (DNM) is a devastating complication of
      cervical or odontogenic infections that can spread downward to the mediastinum
      through anatomic spaces. We report the case of an intravenous drug user who
      presented with rapidly propagating acute pericarditis and DNM as the early
      presentations of pyomyositis of the sternocleidomastoid muscle and deep neck
      infection. The patient was successfully treated with antibiotics and surgical
      drainage. Clinicians should be aware that pathogens injected into the carotid
      sheath may spread to the mediastinum and/or pericardium and manifest as DNM
      and/or pericarditis prior to infectious signs and symptoms at the site of
      injection.

PMID- 18091376
TI  - Expression of OCT4 transcription factor in cutaneous neoplasia.
AB  - The OCT4 transcription factor is a marker of pluripotency and is present in
      embryonic stem cells, primordial germ cells, and several neoplasms including
      seminoma, dysgerminoma, and embryonal carcinoma. Recently, immunohistochemical
      expression of OCT4 protein has been described in the cells within the basal layer
      of normal human and canine epidermis. We have examined a series of basal cell
      carcinomas and adnexal tumors of related histogenesis, in an effort to
      corroborate the above findings and to assess for expression of OCT4 protein in
      neoplasia of the infundibulo-apocrine-sebaceous unit. We analyzed OCT4 expression
      in 115 cutaneous specimens including 26 basal cell carcinomas, 12 benign
      follicular tumors (10 trichoepitheliomas and 2 trichoblastomas), 10 benign
      apocrine tumors, 12 sebaceous hyperplasia lesions, 10 sebaceous adenomas, 4
      sebaceous carcinomas, 13 nevi sebacei of Jadassohn, 8 squamous cell carcinomas
      (including one spindle-cell squamous cell carcinoma), 8 compound melanocytic
      nevi, 5 Merkel cell carcinomas, 3 pilar cysts, 1 scar, 2 nonspecific, mild
      superficial perivascular dermatitis specimens, and 1 non-scarring alopecia. All
      115 specimens examined were negative for OCT4 expression as was adjacent or
      overlying epidermis and follicular epithelium including the bulge region. In
      contrast to previous studies, our data indicate that the OCT4 expression is not
      retained in cutaneous neoplasms derived from basal epidermis or related adnexal
      neoplasms, including lesions of the scalp.

PMID- 18091377
TI  - B7-h4 expression in a range of breast pathology: correlation with tumor T-cell
      infiltration.
AB  - B7-H4, a member of the B7 family, is involved in the regulation of antigen
      specific immune responses. Its expression in a range of breast pathology and
      correlation to the number of CD3 and CD8 tumor infiltrating T-lymphocytes in
      invasive carcinomas were explored. The proportion of B7-H4 positive cells,
      staining pattern, and intensity were evaluated within diagnostic groups (normal
      and benign lesional, potentially premalignant and in situ carcinoma, and invasive
      carcinoma) on archival tissue blocks by immunohistochemistry. The proportion and
      intensity of B7-H4 expression was progressively increased across the major
      diagnostic groups. There was a significant association between a high proportion
      of B7-H4 positive cells in invasive ductal carcinomas and decreased number of
      tumor infiltrating lymphocytes (P=0.002). The cellular distribution of B7-H4
      appears altered in the spectrum of normal to malignant breast. Its overexpression
      may help cancers avoid immune detection.

PMID- 18091378
TI  - YKL-40 expression in benign and malignant lesions of the breast: a methodologic
      study.
AB  - Elevated serum levels of the protein YKL-40 are associated with a poor prognosis
      in patients with solid and hematologic malignancies including breast cancer. The
      aim of this study was to develop a valid reproducible immunohistochemical method
      to visualize YKL-40 expression in normal breast tissue as well as in benign and
      malignant breast lesions. The presence of YKL-40 in breast tissue was verified by
      in situ hybridization and protein extraction procedures. An immunohistochemical
      method was developed and 4 different antibodies directed against YKL-40 were
      tested. Ten patients with normal breast tissue and benign breast lesions and 53
      patients with localized breast carcinomas were analyzed immunohistochemically.
      The presence of YKL-40 in normal epithelial cells as well as in malignant tumor
      cells of the breast was established; however, a difference in staining intensity
      and staining pattern was observed. In normal breast tissue, a weak YKL-40
      immunoreactivity was found in the cytoplasm of the epithelial cells with an
      additional strong dotlike staining between the nucleus and the gland lumen. In
      malignant lesions, 81% of the in situ carcinomas and 64% of the invasive
      carcinomas showed strong diffuse cytoplasmic YKL-40 immunoreactivity. No nuclear
      and membrane staining was found. A subpopulation of cells of macrophage
      morphology in normal breast tissue and in malignant lesions showed strong YKL-40
      immunoreactivity.

PMID- 18091379
TI  - A comparison of plasma versus histologic indices of angiogenic markers in breast
      cancer.
AB  - BACKGROUND: Over-expression of angiogenic growth factors and their receptors, and
      high levels of these molecules in the blood, are a common feature of cancer
      although the relationships between cell expression and plasma levels are unknown.
      We hypothesized a significant correlation between the expression and cellular
      distribution of vascular endothelial growth factor (VEGF), its receptor Flt-1,
      and the angiopoietin receptor Tie-2 with levels of these molecules in the plasma.
      METHODS: The tissue expression of VEGF, Flt-1, and Tie-2 were investigated by
      immunohistochemistry, and plasma levels assessed by enzyme-linked immunosorbent
      assay in 36 patients with breast cancer and 15 with benign breast disease.
      RESULTS: Despite expected significant differences in plasma levels of the
      molecules (P<0.03 to <0.001), no significant differences were found in Tie-2,
      VEGF, and Flt-1 tissue expression between breast cancer and benign disease
      controls. No significant correlations were observed between plasma levels of
      their tissue expression. CONCLUSIONS: Tissue expression of Tie-2, VEGF, and Flt-1
      may not be an overly sensitive tool for assessing abnormalities of coagulation,
      platelet activation, and angiogenesis in human cancer. Plasma markers may not be
      representative of tumor activity, and may not come wholly from tumor cells.
      Instead these markers may be indicative of endothelial dysfunction in cancer
      patients.

PMID- 18091380
TI  - Assessment of a new anti-HER2 monoclonal antibody, SV2-61gamma: a best
      concordance with HER2 FISH.
AB  - It is critical to evaluate the overexpression of human epidermal growth factor
      receptor 2 (HER2) adequately in breast cancer cases. The aim of the present study
      is to assess the characteristics and usefulness of a novel monoclonal antibody,
      clone SV2-61gamma. The overexpression of HER2 was studied on paraffin sections of
      50 breast cancers using a polyclonal antibody assay (HercepTest) and monoclonal
      antibodies (clones SV2-61gamma and CB11). Gene amplification of HER2 was
      determined by fluorescent in situ hybridization (FISH) using a HER2/CEP17DNA
      probe kit. Fifty tumors were scored as 0 (50.0%), 1+ (26.0%), 2+ (4.0%), or 3+
      (20.0%) by immunohistochemistry using a monoclonal antibody, clone SV2-61gamma.
      The specificities of immunohistochemistry were 72.0% for the polyclonal antibody,
      97.0% for SV2-61gamma, and 92.0% for CB11. The concordances with FISH were 78.0%
      for the polyclonal antibody, 98.0% for SV2-61gamma, and 94.0% for CB11. The
      positive predictive value of SV2-61gamma (92.0%) was higher than those of the
      polyclonal antibody (50.0%) and CB11 (79.0%). A monoclonal antibody clone SV2
      61gamma showed very specific staining, with the best concordance with FISH, and
      it is useful for the evaluation of HER2 overexpression.

PMID- 18091381
TI  - Detection of the JC virus genome in lung cancers: possible role of the T-antigen
      in lung oncogenesis.
AB  - The JC virus (JCV) infects a large proportion of the population worldwide and 80%
      to 90% of adults are seropositive and it may be activated in immunodeficient
      patients, resulting in progressive multifocal leukoencephalopathy. Recent reports
      described the possibility of its oncogenetic role in several malignancies. To
      clarify whether JCV might have a potential role in the genesis of lung cancers,
      we investigated the presence of its genome in 62 tumors, along with 23 samples of
      normal lung tissue, targeting the T-antigen, VP, and Agnoprotein by nested
      polymerase chain reaction/Southern blotting followed by direct DNA sequencing.
      Immunohistochemistry was performed to assess links between p53 and beta-catenin
      in lung cancers and the presence of T-antigen. The T-antigen was detected in 25
      of 62 lung cancers but only 4 of 23 normal lung samples (P=0.048). In total, the
      JCV genome was present in 33 of the lung cancers and 10 of the normal samples.
      Furthermore, T-antigen was found in cancer cells in metastatic lymph nodes in 3
      of 4 cases (P=0.042) and was more frequently detected in adenocarcinomas than in
      squamous cell carcinomas (P=0.038). Immunohistochemistry showed significant
      correlations between T-antigen and p53 (P=0.022) and also nuclear detection of
      beta-catenin (P=0.021). It is concluded that the JCV genome might be present in
      cancer cells in approximately half of all Japanese lung cancer cases, and that
      the T-antigen may play a role in oncogenesis of lung cancers through inactivation
      of p53 and dysregulation of the Wnt signaling pathway.

PMID- 18091382
TI  - Coexpression of c-kit and bcl-2 in small cell carcinoma and large cell
      neuroendocrine carcinoma of the lung.
AB  - It has been shown that tyrosine kinase oncoprotein c-kit and antiapoptotic
      molecule bcl-2 are overexpressed in several types of malignancy, including small
      cell carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the
      lung. Whether these 2 molecules are coexpressed in lung neuroendocrine tumors has
      not been investigated. Here, we analyzed immunohistochemical results to determine
      expression and coexpression patterns of c-kit and bcl-2 in the spectrum of lung
      neuroendocrine tumors. Using a polyclonal antibody against c-kit and a monoclonal
      antibody against bcl-2, our data demonstrated that all 7 cases (100%) of SCLC
      included in this study were positive for both c-kit and bcl-2. Among 14 LCNECs, 7
      (50%) stained positive for c-kit and 9 (64%) for bcl-2. All cases of high grade
      neuroendocrine carcinomas (SCLCs and LCNECs) that showed positive staining for c
      kit coexpressed bcl-2. In contrast, all typical and atypical carcinoids (TC and
      AC) were negative for c-kit, and only 1 of 16 (6.3%) TCs and 1 of 6 (16.7%) ACs
      stained positive for bcl-2. These results indicate a progressive increase in the
      frequency of c-kit and bcl-2 expression and coexpression, from carcinoid tumors
      (TC and AC) to LCNEC and to SCLC. High grade neuroendocrine carcinomas are more
      likely to coexpress c-kit and bcl-2 when compared with carcinoid tumors. The high
      frequency of coexpression of these 2 molecules in high grade neuroendocrine
      carcinomas of the lung suggests that they may be involved in the carcinogenic
      pathway, given their important roles in carcinogenesis. Therapeutic targeting on
      both c-kit and bcl-2 molecules might be beneficial in the management of patients
      with high grade neuroendocrine carcinomas of the lung in the future.

PMID- 18091384
TI  - The diagnostic value of TTF-1, CK 5/6, and p63 immunostaining in classification
      of lung carcinomas.
AB  - This study was aimed to evaluate the utility of a panel of antibodies, consisting
      of thyroid transcription factor-1 (TTF-1), p63, and cytokeratins (CK) 5/6 for
      distinguishing between small cell lung carcinoma (SCLC) and nonsmall cell lung
      carcinoma, as well as for identifying glandular or squamous differentiation in
      small tissues obtained by bronchoscopy. Bronchoscopic biopsies of 77 lung
      carcinoma cases with easily recognizable morphologic features were included in
      this study. All the cases were immunohistochemically stained for p63, CK5/6
      [indicators of squamous cell carcinoma (SCC)] and TTF-1 [indicator of SCLC and
      adenocarcinoma (AC)]. Although, 28 SCLC displayed TTF-1 positive, p63 negative
      immunoprofile, most of the SCC (32/39) had the opposite immunoprofile. All of the
      10 ACs were negative for p63 and most of them (8/10) were negative for CK5/6. p63
      and CK 5/6 seem to be useful for differentiating AC and SCLC from SCC with 100%
      specificity and 82% sensitivity, 89% specificity and 79% sensitivity,
      respectively. It seems that to achieve histologic typing of lung cancer as
      accurate as possible, TTF-1 in combination with p63 and CK 5/6 might be useful
      components of immunohistochemical analysis of poorly differentiated lung
      carcinomas in biopsy tissues.

PMID- 18091383
TI  - Diagnostic value of CDX-2 and TTF-1 expressions in separating metastatic
      neuroendocrine neoplasms of unknown origin.
AB  - Histomorphologic features and routine endocrine immunohistochemical (IHC) markers
      do not differentiate neuroendocrine tumors (NETs) in relation to their location,
      making it difficult to establish the site of origin of a metastatic neoplasm.
      Site-specific markers would be useful, particularly when examining small
      biopsies. CDX-2 and thyroid transcription factor-1 (TTF-1) are transcription
      factors that have been recently proposed as IHC markers of intestinal and
      pulmonary adenocarcinomas, respectively. However, their expression in NETs has
      not been widely studied. The objective of this study is to evaluate the
      expression of TTF-1 and CDX-2 in NETs and their potential usefulness in
      distinguishing gastrointestinal and pulmonary NETs from other sites. We performed
      an IHC study on formalin-fixed, paraffin-embedded sections from 155 primary NETs,
      including 60 pulmonary, 60 gastrointestinal, 30 pancreatic, and 5 NETs from other
      sites. In addition, we evaluated 13 metastatic NETs, including 11 cases of
      gastrointestinal and 2 of pulmonary origin. In this study, CDX-2 was expressed in
      28/60 (47%) of gastrointestinal NETs with the following results: 11/11 (100%)
      appendiceal, 12/14 (86%) small intestinal, 3/4 (75%) colonic, 2/11 (18%) rectal,
      and 0/20 (0%) gastric. TTF-1 was expressed in pulmonary carcinoid tumors in 13/30
      (43%) and in 27/30 (90%) pulmonary small cell carcinomas. NETs of other origins
      (pancreas, skin, ovary, and thymus) were negative for both TTF-1 and CDX-2.
      Metastatic neuroendocrine neoplasms of intestinal origin were positive for CDX-2
      and negative for TTF-1. In conclusion, CDX-2 expression is highly specific in
      identifying NETs of intestinal origin and TTF-1 expression is helpful in
      identifying NETs of pulmonary origin, which can be quite useful in the diagnosis
      of metastatic NETs of unknown origin.

PMID- 18091385
TI  - Expression of immunohistochemical markers in primary and metastatic malignant
      melanoma: a comparative study in 70 patients using a tissue microarray technique.
AB  - Melanoma can show a broad spectrum of immunoreactivity and exhibit aberrant
      expression of antigens or changes in immunophenotype, particularly at metastatic
      sites. We studied 70 primary melanomas and their metastases with a broad panel of
      immunohistochemical markers using a tissue microarray technique to determine
      possible antigenic shift between the primary lesions and their metastases.
      Representative tissue cores were taken and processed from each case, and the
      tissue microarrays were stained by standard methods using antibodies to vimentin,
      bcl-2, CD117, carcinoembryonic antigen, epithelial membrane antigen, S-100
      protein, HMB-45, cytokeratin AE1/AE3, Melan-A, TTF-1, CD99, and tyrosinase.
      Histologically, all the melanomas were of the classic epithelioid type. A slight
      increase in the expression of Melan-A was noted in metastatic lesions as opposed
      to the primary tumors (63% vs. 48.4%). Expression of other melanoma-associated
      markers, including S-100 protein and tyrosinase was only slightly decreased at
      metastatic sites as opposed to the primary tumor. Increased aberrant expression
      of epithelial-associated markers, including epithelial membrane antigen and
      cytokeratin AE1/AE3 was also noted in the metastases. bcl-2, CD117, and TTF-1
      also showed a modest increase in antigenic expression at metastatic sites over
      the primary lesions. The results of this study demonstrated minimal antigenic
      shift between primary and metastatic melanoma for some of the more conventional
      melanocytic markers, it showed increased expression of aberrant markers and
      oncogene expression at metastatic sites.

PMID- 18091386
TI  - The mucin expression profile of endometrial carcinoma and correlation with
      clinical-pathologic parameters.
AB  - Mucin expression patterns have been studied in tumors from various sites.
      Previous studies have shown an association of MUC1 with poor prognosis and MUC2
      and MUC5AC with a mucinous phenotype. The pattern of mucin expression in
      endometrial carcinomas has not been documented in a large series. We determined
      the mucin expression profile in endometrial carcinomas and evaluated the
      relationship between mucin expression and clinical-pathologic parameters. A
      tissue microarray of 310 cases of endometrial carcinoma with known clinical
      outcome was constructed from formalin-fixed, paraffin-embedded donor blocks using
      two 0.6 mm cores from each tumor. Sections were stained with monoclonal
      antibodies against MUC1, MUC2, MUC4, MUC5AC, and MUC6. Staining was considered
      positive if greater than or equal to 5% of cells stained positively in either
      core. Mucin expression was correlated with tumor type, histologic grade,
      International Federation Gynecology and Obstetrics stage, lymph node involvement,
      depth of myometrial invasion, patient age, ethnicity, and clinical outcome. MUC1
      was expressed in 267/310 (86.1%) of endometrial carcinomas, MUC2 in 2/310 (0.6%),
      MUC4 in 73/310 (23.5%), MUC5AC in 1/310 (0.3%), and MUC6 in 4/310 (1.2%).
      Endometrioid endometrial carcinoma showed a higher rate of MUC1 expression than
      nonendometrioid endometrial carcinoma (227/258, 88.0% vs. 39/52, 75.0%, P=0.01).
      No significant differences in any of the mucins were noted among the other end
      points evaluated. Mucin expression did not correlate with tumor grade, stage, or
      patient outcome.

PMID- 18091387
TI  - Low expression of FHIT and PTEN correlates with malignancy of gastric carcinomas:
      tissue-array findings.
AB  - To clarify the roles of FHIT (fragile histidine triad) and PTEN (phosphatase and
      tensin homology deleted from human chromosome 10) expression in the genesis and
      progression of gastric cancers, we examined expression of FHIT and PTEN on tissue
      microarray containing gastric normal mucosa (n=49), adenoma (n=49), noncancerous
      mucosa adjacent to carcinoma (n=84) and carcinoma (n=249) by
      immunohistochemistry. Their expression was compared with clinicopathologic
      parameters of tumors, including expression of p53 and cysteine protease protein
      32 as well as survival time of patients with carcinoma. The results showed
      expression of FHIT and PTEN were lower in gastric carcinoma than those in normal
      mucosa, noncancerous mucosa adjacent to carcinoma and adenoma of the stomach
      (P<0.05). FHIT and PTEN expression showed a significantly negative association
      with depth of invasion, lymphatic invasion, and lymph node metastasis, liver
      metastasis, and Union Internationale Contre le Cancer staging of gastric
      carcinoma (P<0.05). Intestinal-type gastric carcinomas highly expressed FHIT and
      PTEN protein, compared with diffuse-type ones (P<0.05). Expression of FHIT and
      PTEN were positively related with expression of p53 and cysteine protease protein
      32 in gastric carcinoma (P<0.05), as well as favorable prognosis of the patients
      with the tumors (P<0.05). There was positive relationship between FHIT and PTEN
      expression in gastric carcinoma (P<0.05). It was suggested that down-regulated
      expression of FHIT and PTEN contributed to gastric carcinogenesis possibly by
      involving in the imbalance between apoptosis and proliferation of cells. Their
      altered expression underlay the molecular basis of invasion, metastasis,
      differentiation of gastric carcinoma.

PMID- 18091388
TI  - Her-2 protein expression, cellular localization, and gene amplification in
      colorectal carcinoma.
AB  - This study was sought to evaluate the relationship between Her-2 protein
      expression, cellular localization, gene amplification, and other
      clinicopathologic parameters in colorectal carcinomas. Her-2 protein expression
      and gene amplification were assessed in paraffin sections from 106 primary
      colorectal adenocarcinoma cases using immunohistochemistry and fluorescence in
      situ hybridization. Both membranous and cytoplasmic immunostaining was evaluated.
      The results were correlated with each other and with tumor grade, stage, and
      overall survival. Membranous and cytoplasmic protein expression was identified in
      6 (5.6%) and 13 (12.26%) cases, respectively. Gene amplification was detected in
      4 (3.7%) cases. There was a high concordance between membranous protein
      expression and gene amplification (kappa=0.791). No apparent association with any
      of the clinicopathologic parameters was identified. Membranous Her-2 protein
      expression and gene amplification are encountered in a small subset of colorectal
      carcinomas and are highly concordant events. Cytoplasmic protein expression might
      be either artifactual or it might represent a cross-reacting protein or a
      precursor form of the mature protein.

PMID- 18091389
TI  - Diagnostic utility of CD44 standard, CD44v6, and CD44v3-10 expression in
      adenocarcinomas presenting in serous fluids.
AB  - CD44 is an 85 to 90 kd integral transmembrane protein encoded by a single 20-exon
      gene located on the short arm of chromosome 11. In the standard form (CD44s), 10
      of the 20 exons are transcribed. Multiple variant isoforms exist (CD44v1-10)
      which arise from alternate mRNA splicing of the remaining 10 exons. In contrast
      to the standard form of CD44, which is almost ubiquitously expressed, splice
      variants are highly restricted in their expression in normal or malignant
      tissues. The purpose of this study was to evaluate the extent to which metastatic
      adenocarcinomas in effusions express CD44s, CD44v6, and CD44v3-10 and to assess
      their diagnostic utility in distinguishing reactive mesothelial cells from
      adenocarcinomas. Archival paraffin-embedded cell blocks of serous fluids from 23
      cases of benign effusions containing reactive mesothelial cells and 45 cases of
      malignant effusions with metastatic adenocarcinoma (18 ovarian, 11 pulmonary, 9
      gastrointestinal, and 7 breast) were retrieved from the surgical pathology files.
      The cytopathology of all cases was reviewed to confirm the diagnosis.
      Immunohistochemistry was performed on all cases using antibodies for CD44s,
      CD44v6, and CD44v3-10 (Bender MedSystems, CA). Positive staining was defined as
      distinct linear membrane staining. Strong staining in at least 10% of the tumor
      cells was required to consider the case positive for the particular marker. In
      benign effusions mesothelial cells expressed CD44s in 22 cases (96%), CD44v6 in 1
      cases (4%) and CD44v3-10 in 0 cases (0%). In contrast neoplastic cells in
      malignant effusions expressed CD44s in 11 cases (24%), CD44v6 in 21 cases (47%),
      and CD44v3-10 in 39 cases (87%). We concluded that CD44s and CD44v3-10 are useful
      markers that can be applied to cytologic specimens. CD44s immunostaining can be
      used as a reliable marker to identify reactive mesothelial cells, meanwhile
      CD44v3-10 immunostaining can detect majority of adenocarcinomas in malignant
      effusions.

PMID- 18091390
TI  - Assessment of two automated imaging systems in evaluating estrogen receptor
      status in breast carcinoma.
AB  - Immunohistochemical staining for estrogen receptor (ER) status is widely used in
      the management of breast cancer. These stains have traditionally been scored
      manually, which results in generally good agreement among observers when the
      cases are strongly positive. However, significant interobserver and intraobserver
      differences in scoring can occur in borderline or weakly staining cases.
      Recently, automated systems have been proposed to provide a more sensitive and
      objective method of ER quantification. The ChromaVision Automated Cellular
      Imaging System and the Applied Imaging Ariol SL-50 quantify the color intensity
      of the immunoreactive product. To assess the accuracy of these 2 automated
      systems and to compare them to one another and to manual scoring, we performed
      immunostaining for ER on 64 cases of breast cancer. The percentages of positive
      cells were scored manually by 4 pathologists and by the 2 imaging systems. A
      discrepancy in scoring was defined as that which resulted in the reclassification
      of a case from negative to positive or vice versa. Our results showed significant
      agreement between the 2 automated systems. When automated scores were compared
      with the manual scores, only 5 of the 64 cases (7%) were discrepant. In 4 of
      these, the percentage of cells staining for ER was low (0% to 20%). Overall, the
      2 systems were comparable, and discrepant results were most frequently seen when
      analyzing tumors with low levels of ER positive cells.

PMID- 18091391
TI  - Computer-assisted immunohistochemical analysis of cervical cancer biomarkers
      using low-cost and simple software.
AB  - The study of biomarkers by immunohistochemistry (IHC) for cervical cancer and
      intraepithelial lesions is a promising field. However, manual interpretation of
      IHC and reproducibility of the scoring systems can be highly subjective. In this
      article, we present a novel and simple computer-assisted IHC interpretation
      method based on cyan-magenta-yellow-black (CMYK) color format, for tissues with
      diaminobenzidine cytoplasmatic staining counterstained with methyl green. This
      novel method is more easily interpreted than previous computer-assisted methods
      based on red-green-blue (RGB) color format and presents a strong correlation with
      the manual H-score. It is simple, objective, and requires only low-cost software
      and minimal computer skills. Briefly, a total of 67 microscopic images of
      cervical carcinoma, normal cervix, and negative controls were analyzed in Corel
      Photo Paint X3 software in CMYK and RGB color format, and compared with manual H
      score IHC assessments. The clearest and best positive correlation with the H
      score was obtained using the image in CMYK color format and crude values of
      magenta color (Spearman correlation coefficient=0.84; agreement of 93.33%,
      P<0.001). To obtain this value, only 3 steps were necessary: convert the image to
      CMYK format, select the area of interest for analysis, and open the color
      histogram tool to visualize the magenta value.

PMID- 18091392
TI  - Tissue fixation effects on immunohistochemical staining of caspase-3 in brain
      tissue.
AB  - Fixation methods for tissue often vary amongst clinical and research
      laboratories. To evaluate the effects of fixation method on studies of brain
      tissue, we examined immunohistochemical outcomes amongst 2 fixatives, 4 caspase-3
      antibodies, and 2 species (human infants and piglets). Fixatives were 10% neutral
      buffered formalin (NBF) or 10% NBF and glacial acetic acid (FAA). Antibodies for
      caspase-3 were commercially obtained and included 2 for active caspase-3, and 2
      for procaspase-3 (CASP3 and CPP32). Immunohistochemical staining of caspase-3
      varied with fixation method, with the greatest effect of fixation method observed
      for the active caspase-3 antibodies and this effect was present in both species.
      In NBF-fixed tissue, active caspase-3 immunoreactivity was only visible
      microscopically, and was specific to neuronal cell bodies. In FAA-fixed tissue,
      active caspase-3 immunoreactivity was visible macroscopically, and predominantly
      present in fiber tracts and fasciculi compared with neuronal bodies. Fixation and
      species differences were also identified for the procaspase-3 antibodies, CASP3
      and CPP32, where FAA-fixed pig tissue showed abundant staining of blood vessels
      that were not observed in the NBF-fixed pig tissue or in the human tissue. This
      study characterizes differences in immunohistochemical outcomes using
      commercially available antibodies for caspase-3, according to tissue fixation
      method and species.

PMID- 18091393
TI  - ZAP70 expression assessed by immunohistochemistry on peripheral blood: a simple
      prognostic assay for patients with chronic lymphocytic leukemia.
AB  - The somatic hypermutational (SHM) status of the immunoglobulin heavy-chain
      variable (IgVH) gene is a powerful prognostic factor in patients with chronic
      lymphocytic leukemia (CLL). However, IgVH SHM analysis is not well-suited to
      routine use in the clinical diagnostic laboratory. ZAP70 expression is a
      potential surrogate for the absence of SHM. Given the current problems with the
      standardization of ZAP70 assessment by flow cytometry, we sought an alternative
      approach, using immunohistochemistry (IHC). The utility of IHC is largely
      restricted to tissues, precluding its routine application to most patients with
      CLL who are typically diagnosed based upon peripheral blood (PB) findings.
      Accordingly, we developed an IHC assay that can be performed on PB. Enriched PB
      mononuclear cells from 29 patients with CLL were analyzed for ZAP70 expression by
      IHC on paraffin-embedded cell blocks, using standard techniques. IgVH SHM
      analysis was performed on all cases, and clinical features recorded. Seventeen
      specimens (59%) were negative for ZAP70 expression and 12 (41%) were positive for
      ZAP70 expression. SHM was evident in 20 specimens (69%), and absent in 9 (31%).
      Seventy-six percent of the specimens (22/29) displayed "concordant" ZAP70 and SHM
      results, in that 15 (52%) were SHM-positive/ZAP70 negative, whereas 7 (24%) were
      SHM-negative/ZAP70 positive. ZAP70 expression in this small cohort correlated
      with poor clinical outcome. Importantly, IHC analysis of ZAP70 in PB is a simple,
      reliable, robust assay that may have a valuable role in the routine clinical
      laboratory assessment of patients with CLL.

PMID- 18091394
TI  - Myxoid liposarcoma with cartilaginous differentiation: identification of the same
      type II TLS-CHOP fusion gene transcript in both lipogenic and chondroid
      components.
AB  - Heterologous differentiation in adipocytic tumors is a rare phenomenon. Only 4
      cases of myxoid liposarcoma (MLS) with cartilaginous differentiation were thus
      far reported without confirmatory molecular assays. We describe a primary MLS
      with chondroid differentiation that affected the left thigh of a 47-year-old man.
      Histologically, multiple sharply demarcated chondroid nodules were embedded among
      the classic MLS area. By reverse transcription-polymerase chain reaction, the
      identical type II TLS-CHOP fusion gene transcripts were detected in both the
      liposarcomatous and microdissected chondroid tumor cells. Our case confirms the
      actual existence of MLS with cartilaginous differentiation and the neoplastic
      nature of chondroid component.

PMID- 18091395
TI  - CD4+/CD56+ hematodermic neoplasm: presentation of 2 cases and review of the
      concept of an uncommon tumor originated in plasmacytoid dendritic cells
      expressing CD123 (IL-3 receptor alpha).
AB  - CD4/CD56 hematodermic neoplasm is a rare neoplasm presenting with cutaneous
      nodules, lymphadenopathy, bone marrow infiltration, and an aggressive clinical
      course. Recently, the plasmacytoid dendritic cell origin of this neoplasm has
      been demonstrated. Plasmacytoid dendritic cell is a hematopoietic-derived cell
      implicated in the regulation of innate and adaptive cell immunity and in the
      production of certain regulatory cytokines. Recently it has been demonstrated
      that these cells express cell surface markers such as IL-3 receptor alpha
      (CD123). In the present report, we describe the clinical, histologic, and
      immunohistochemical characteristics of 2 cases of CD4/CD56 hematodermic neoplasm.
      Both patients were male and the age at the time of diagnosis was 36 and 75 years,
      respectively. Clinical findings were limited to the skin and consisted of
      multiple cutaneous nodules located in the thorax and extremities, some of them
      ulcerated. Histologically, the tumors were characterized by a nonepidermotropic,
      dermal and subdermal infiltration of homogeneous medium-sized cells resembling
      lymphoblasts or myeloblasts. Immunohistochemical characterization of the tumors
      showed expression of CD4, CD56, CD43, and CD123, whereas CD8, CD20, and MPO were
      negative. Immunoreactivity for CD3, which has been described in rare occasions,
      was found only in one of the cases. This characteristic profile in addition to
      the expression of CD123, which was detected in both cases, can be used as
      valuable tools in the diagnosis of this rare neoplasm.

PMID- 18091396
TI  - A tribute to Edmund H. Sonnenblick, MD: 1932-2007.

PMID- 18091397
TI  - Pathophysiology, diagnosis, and treatment of orthostatic hypotension and
      vasovagal syncope.
AB  - Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17%
      of patients in acute care settings. Moreover, OH may be more prevalent in the
      elderly due to the increased use of vasoactive medications and the concomitant
      decrease in physiologic function, such as baroreceptor sensitivity. OH may result
      in the genesis of a presyncopal state or result in syncope. OH is defined as a
      reduction of systolic blood pressure (SBP) of at least 20 mm Hg or diastolic
      blood pressure (DBP) of at least 10 mm Hg within 3 minutes of standing. A review
      of symptoms, and measurement of supine and standing BP with appropriate clinical
      tests should narrow the differential diagnosis and the cause of OH. The fall in
      BP seen in OH results from the inability of the autonomic nervous system (ANS) to
      achieve adequate venous return and appropriate vasoconstriction sufficient to
      maintain BP. An evaluation of patients with OH should consider hypovolemia,
      removal of offending medications, primary autonomic disorders, secondary
      autonomic disorders, and vasovagal syncope, the most common cause of syncope.
      Although further research is necessary to rectify the disease process responsible
      for OH, patients suffering from this disorder can effectively be treated with a
      combination of nonpharmacologic treatment, pharmacologic treatment, and patient
      education. Agents such as fludrocortisone, midodrine, and selective serotonin
      reuptake inhibitors have shown promising results. Treatment for recurrent
      vasovagal syncope includes increased salt and water intake and various drug
      treatments, most of which are still under investigation.

PMID- 18091398
TI  - Women, their age, and their cholesterol values.

PMID- 18091399
TI  - Platelet inhibitors: what are the data in women?
AB  - Cardiovascular disease is the leading cause of disability and mortality among
      women in the United States. However, relative to their representation among the
      overall population of patients presenting with acute coronary syndromes, women
      have been underrepresented in clinical trials of treatment strategies for acute
      coronary syndromes. In general, subgroup analyses and meta-analyses of the data
      from the major treatment trials have demonstrated similar treatment effects among
      women and men, but questions recently have been raised regarding the role and
      effect of antiplatelet therapy in the treatment of women. This article will
      review the use of antiplatelet therapy in women from the perspective of both
      primary and secondary prevention using as a focus for discussion recent
      randomized clinical trial data and registry observations of the potential
      benefits and risks of antiplatelet therapy in women.

PMID- 18091400
TI  - Confusion in revascularization: are women different and why?
AB  - Cardiovascular disease is the leading cause of death in women in most developed
      countries of the world. Even though cardiovascular deaths of men in the United
      States have been declining, until recently the number of cardiovascular deaths in
      US women was on the rise, with 1 in 3 women dying from heart disease. Over the
      last 30 years numerous studies have reported sex differences in the epidemiology,
      prevention, diagnosis, and clinical manifestations of coronary artery disease. A
      higher morbidity and mortality were also noted in women versus men undergoing
      revascularization during this early period. This has mainly been attributed to
      the fact that women have more comorbid conditions by the time that they are
      referred for revascularization. These conditions include increased age,
      hypertension, diabetes (metabolic syndrome), heart failure, renal disease,
      peripheral vascular disease, and worse lipid profile. With improvements of both
      surgical techniques and percutaneous coronary intervention, morbidity and
      mortality rates have decreased in women undergoing revascularization. However,
      there are now questions surrounding percutaneous coronary intervention
      strategies, particularly with drug eluting stents. More recent advances in
      coronary bypass graft surgery techniques, both off- and on-pump, and analysis of
      prospective and retrospective data have shown a clearly improved survival rate in
      patients undergoing coronary bypass graft surgery and the persistence of a
      durable result.

PMID- 18091401
TI  - Cardiac rehabilitation barriers and opportunities among women with cardiovascular
      disease.
AB  - Cardiac rehabilitation is a key component of the comprehensive care of the 79.4
      million adults in the United States with one or more forms of cardiovascular
      disease. Only a fraction of eligible candidates complete cardiac rehabilitation
      and women are at a significantly higher risk for underutilizing this safe and
      effective secondary prevention intervention. This article reviews the complex
      array of barriers to cardiac rehabilitation, with a focus on those factors that
      are unique to women. The Healthcare Utilization Model is used as a theoretical
      framework to categorize these barriers into environmental, physician, and patient
      level categories. These barriers, although challenging for both patients and
      healthcare professionals, provide opportunities for change. Actionable evidence
      based recommendations for healthcare professionals include making changes in
      health policy, using proven performance improvement methodologies to increase
      referral and enrollment, using interdisciplinary models of communication, and
      enhancing cardiac rehabilitation program attributes reflective of women's
      preferences and needs.

PMID- 18091402
TI  - PFO and stroke: what are the data?
AB  - Patent foramen ovale (PFO) is a frequent finding on echocardiography and occurs
      in over 25% of the population. In young patients with cryptogenic stroke, the
      frequency is much higher suggesting paradoxical embolization may be responsible
      for the clinical events. There are conflicting data from studies examining the
      association between PFO and stroke. The combination of atrial septal aneurysm and
      PFO, and PFO size and severity of right-to-left shunt may add additional risk but
      again the data are insufficient for definite conclusions. Available information
      suggests no difference in subsequent stroke in patients with PFO treated with
      aspirin or warfarin for secondary prevention. Endovascular closure is technically
      feasible, but not without the possibility of periprocedural complications.
      Comparison of medical and endovascular closure of PFOs in patients with stroke is
      ongoing in 2 major randomized trials.

PMID- 18091403
TI  - What aspects of hospital culture influence quality?

PMID- 18091404
TI  - A novel pathway for the management of hypertension for hospitalized patients.
AB  - About 65 million Americans, one fourth of the adult population in the United
      States, and over 1 billion people worldwide have hypertension (HTN). HTN
      therefore is present in 1 of every 4 patients admitted to any US hospital.
      Surprisingly, no guidelines are available for the management of inpatient HTN.
      Based on a comprehensive search of the literature we are proposing a pathway for
      the management of HTN in nonpregnant hospitalized patients. The pathway provides
      a definition and clinical assessment of HTN for patients admitted to the
      hospital. The assessment is followed by an organ/system based therapeutic
      approach specifying timing, blood pressure goals, recommended antihypertensive
      drug therapy and the sequence of add-on drugs. The pathway specifically discusses
      assessment and management of HTN in patients with (1) acute aortic syndrome, (2)
      acute neurologic syndrome, (3) acute coronary syndrome, (4) congestive heart
      failure, (5) renal failure, and (6) secondary forms. Finally, the pathway
      provides a step by step recommendation for the management of in hospital HTN and
      of hypertensive emergencies.

PMID- 18091405
TI  - Evaluation of patients with methamphetamine- and cocaine-related chest pain in a
      chest pain observation unit.
AB  - OBJECTIVE: Risk of acute coronary events in patients with methamphetamine and
      cocaine intoxication has been described. Little is known about the need for
      additional evaluation in these patients who do not have evidence of myocardial
      infarction after the initial emergency department evaluation. We herein describe
      our experience with these patients in a chest pain unit (CPU) and the rate of
      cardiac-related chest pain in this group. METHODS: Retrospective analysis of
      patients evaluated in our CPU from January 1, 2000 to December 16, 2004 with a
      history of chest pain. Patients who had a positive urine toxicologic screen for
      methamphetamine or cocaine were included. No patients had ECG or cardiac injury
      marker evidence of myocardial infarction or ischemia during the initial emergency
      department evaluation. A diagnosis of cardiac-related chest pain was based upon
      positive diagnostic testing (exercise stress testing, nuclear perfusion imaging,
      stress echocardiography, or coronary artery stenosis >70%). RESULTS: During the
      study period, 4568 patients were evaluated in the CPU. A total of 1690 (37%) of
      patients admitted to the CPU underwent urine toxicologic testing. The result of
      urine toxicologic test was positive for cocaine or methamphetamine in 224 (5%).
      In the 2871 patients who underwent diagnostic testing for coronary artery disease
      (CAD), 401 (14%) were found to have positive results. There was no difference in
      the prevalence of CAD between those with positive result for toxicology screens
      (26/156, 17%) and those without (375/2715, 13%, RR 1.2, 95% CI 0.8-1.7).
      CONCLUSION: These findings suggest a relatively high rate of CAD in patients with
      methamphetamine and cocaine use evaluated in a CPU.

PMID- 18091406
TI  - Emergency Department greeters reduce door-to-ECG time.
AB  - INTRODUCTION: Screening for Acute Coronary Syndrome in chest pain patients can be
      initiated with a 12-lead electrocardiogram (ECG). Current American College of
      Cardiology/American Heart Association guidelines recommends getting an ECG
      performed and reviewed within 10 minutes of the time these patients present to
      the Emergency Department (ED). One innovative method to improve door-to-ECG time
      is by placing a trained greeter in the triage section of the ED. METHODS: This
      study was conducted over a 3-week period from September to October 2006, in a
      large urban academic medical center. The greeter was stationed in the triage
      area, and screened every patient entering the ED for the following
      symptoms/complaints: chest pain, shortness of breath, acute mental status changes
      in nursing home patients, dizziness, and nausea with or without vomiting in
      diabetic patients. The greeter obtained the ECG in the qualified patients, or
      alerted the triage. Data was collected on ECGs for all ED patients who presented
      with the above complaints in the absence of a greeter. RESULTS: In the 3 weeks of
      the study, data was collected on 126 cases. The greeter had obtained 40 ECGs, and
      86 ECGs were done without the greeter. The average door-to-ECG times were
      significantly different between the groups. The study found 8.8 minutes in the
      greeter group versus 29.6 minutes in the nongreeter group (P = 0.000).
      CONCLUSION: ED triage greeter can be effectively used to obtain timely ECGs in
      suspected Acute Coronary Syndrome patients.

PMID- 18091407
TI  - Evaluation of proton pump inhibitor use in patients with acute coronary syndromes
      based on risk factors for gastrointestinal bleed.
AB  - BACKGROUND: Use of proton pump inhibitor (PPI) reduces the risk of
      gastrointestinal (GI) bleeding, and is generally recommended for high GI risk
      patients taking nonsteroidal anti-inflammatory agents. Aspirin and/or
      anticoagulants have been identified as increasing the risk of GI bleeding,
      whereby use of PPI could reduce this risk. The use of PPI in routine practice is
      not well defined, especially in patients with acute coronary syndromes (ACS) who
      require one or several antithrombotic drugs. METHODS: We analyzed the Pravastatin
      or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial
      Infarction (PROVE IT-TIMI) 22 trial database, which enrolled patients who had
      been hospitalized for ACS. Patients were to be treated with aspirin, and received
      clopidogrel and/or warfarin at the discretion of the treating physician. We
      analyzed the use of PPI at baseline, which was not specified in the protocol,
      according to prior known GI risk factors. RESULTS: Of the 4162 patients enrolled,
      781 (18.8%) received PPI during the course of this study. The use ranged from 14%
      to 67% across the number of GI risk factors of 0 to > or =4 (P < 0.0001).
      Individual factors most associated with increased use of PPI were a prior GI
      event (RR = 2.3, P < 0.001) and use of anticoagulants (RR = 1.49, P < 0.001), but
      not dual antiplatelet therapy. CONCLUSION: Use of PPI following ACS is modest,
      although it did increase with an increasing number of previously identified GI
      risk factors. Further, larger studies are warranted to validate prior, or
      identify new, risk factors as predictors of long-term bleeding, and improve
      awareness of GI bleeding risk such that use of PPI could be optimized.

PMID- 18091408
TI  - Implementing cardiac risk-factor case management: lessons learned in a county
      health system.
AB  - METHODS: Case-management (CM) can positively influence chronic disease care by
      facilitating guideline-concordant interventions that improve outcomes through
      intensive, individualized, longitudinal care. Implementation of CM, however, is
      difficult. We have identified lessons learned from a cardiovascular risk
      reduction CM program that may aid future CM implementation. INTRODUCTION: Heart
      to Heart is both a clinical trial and program dissemination project implementing
      CM for persons at elevated risk of coronary heart disease (CHD) events in a
      multiethnic, low-income population in a county health system. Patients were
      randomized to CM plus usual primary care (N = 212) or primary care alone (N =
      207). CM patients received face-to-face nurse and dietitian visits (mean of 14
      hours) over 17 months. Visits emphasized behavior change, risk-factor monitoring,
      and guideline-based pharmacotherapy. A total of 341 patients (81%) were available
      for follow-up. This CM model is currently transitioning to a County-run program.
      RESULTS: Findings demonstrated statistically significant reductions in mean
      Framingham Risk for CM versus usual primary care (1.56% absolute decrease in 10
      year CHD risk, P = 0.007). Favorable changes were noted across most major CHD
      risk factors. Lessons learned are the need for the following: (1) Strategies for
      implementing CM in low-income, ethnically-diverse populations, (2) Methods for
      developing clinically more effective CM, and (3) Approaches to increase the
      efficiency of cardiovascular CM. CONCLUSIONS: CM for cardiac risk factors faces
      notable implementation barriers, particularly in County health systems. Specific
      implementation solutions recommended may help confront these barriers and improve
      diffusion of this evidence-based and patient centered model of care.

PMID- 18091409
TI  - Percutaneous coronary intervention in the elderly for myocardial infarction in
      the poststent era.
AB  - BACKGROUND: Patients of > or =70 years of age and with acute coronary syndrome
      accumulate more risk factors with poor outcomes. Surgical revascularization is
      associated with increased mortality when compared with young population. The aim
      of this study was to communicate a single, small center experience, of
      percutaneous coronary intervention in the elderly in poststent era. PATIENTS AND
      METHODS: Seventy-five consecutive patients, > or =70 years of age, with
      myocardial infarction (MI) at admission, between January, 2005 and November,
      2006. We evaluate major and minor events during hospitalization. RESULTS:
      Patients (64%) were male, 53.3% hypertension, 38.7% diabetes mellitus. Clinical
      presentation was: ST-segment elevation MI 53.3% and 5.3% with cardiogenic shock.
      Mean left ventricle ejection fraction was 48.5 +/- 18%. The procedure was
      successful in all the cases and culprit lesions received at least one stent in
      93.4%. In-hospital major events were registered in 6.6% of cases: 3 (4%) death
      and 2 (2.6%) nonfatal MI; minor complications were registered in 5.2% of cases.
      CONCLUSION: Percutaneous coronary intervention in patients >70 years of age
      during MI is feasible and safe, with low rates of complications.

PMID- 18091410
TI  - A tale of two toxicants: lessons from Minamata and Liaoning.

PMID- 18091411
TI  - Long-term exposure to methylmercury and neurologic signs in Minamata and
      neighboring communities.
AB  - BACKGROUND: It is well known that large-scale poisonings caused by methylmercury
      occurred in Japan (Minamata, in the 1950s) and Iraq. However, in contrast to
      Iraq, there have been few sound epidemiologic studies in Minamata. We evaluated
      the effect of methylmercury on neurologic signs using data from a 1971 population
      based study. METHODS: Villages in 3 areas were selected for study: the Minamata
      area (a high-exposure area), the Goshonoura area (a medium-exposure area), and
      the Ariake area (a low-exposure area). We used place of residence as the exposure
      indicator. We examined associations between methylmercury exposure and the
      following neurologic signs measured on clinical examination: paresthesia of whole
      body, paresthesia of extremities, paresthesia around the mouth, ataxia,
      dysarthria, tremors, and pathologic reflexes. RESULTS: Total population was 1120
      in the high-exposure villages, 1845 in the medium-exposure villages, and 1165 in
      the low-exposure villages. In the Minamata area, 87% (n=833) of the eligible
      population (age 10 years and older) participated in the 1971 investigations, in
      the Goshonoura area, 93% (n = 1450), and in the Ariake area, 77% (n = 755).
      Compared with subjects in the Ariake area, the subjects in the Minamata area
      manifested neurologic signs more frequently. The highest prevalence odds ratio
      was observed for paresthesia around the mouth (110; 95% confidence interval = 16
      820). Although residents in the Goshonoura area had been exposed less heavily
      than those in the Minamata area, Goshonoura residents also had increased
      prevalence of neurologic signs. CONCLUSION: Long-term exposure to methylmercury
      has a strong adverse impact on neurologic signs among residents in a local
      community.

PMID- 18091412
TI  - The delayed appearance of a mercurial warning.
AB  - The publication of a 1971 study from Japan on chronic methylmercury poisoning in
      adults provides an occasion to reexamine the history of Minamata disease and its
      social and political repercussions. Research findings were suppressed or held
      back due to controversies that were tearing the Japanese scientific community
      apart. Similar controversies occurred outside of Japan as well. Only now are the
      long-term adverse effects of environmental methylmercury exposure becoming clear.
      The delayed release of the 1971 results therefore reminds us as epidemiologists
      of our obligation, even in the presence of scientific uncertainty, to call
      attention to preventable risks.

PMID- 18091413
TI  - Cancer mortality in a Chinese population exposed to hexavalent chromium in
      drinking water.
AB  - BACKGROUND: In 1987, investigators in Liaoning Province, China, reported that
      mortality rates for all cancer, stomach cancer, and lung cancer in 1970-1978 were
      higher in villages with hexavalent chromium (Cr+6)-contaminated drinking water
      than in the general population. The investigators reported rates, but did not
      report statistical measures of association or precision. METHODS: Using reports
      and other communications from investigators at the local Jinzhou Health and Anti
      Epidemic Station, we obtained data on Cr+6 contamination of groundwater and
      cancer mortality in 9 study regions near a ferrochromium factory. We estimated:
      (1) person-years at risk in the study regions, based on census and population
      growth rate data, (2) mortality counts, based on estimated person-years at risk
      and previously reported mortality rates, and (3) rate ratios and 95% confidence
      intervals. RESULTS: The all-cancer mortality rate in the combined 5 study regions
      with Cr+6-contaminated water was negligibly elevated in comparison with the rate
      in the 4 combined study regions without contaminated water (rate ratio = 1.13;
      95% confidence interval = 0.86-1.46), but was somewhat more elevated in
      comparison with the whole province (1.23; 0.97-1.53). Stomach cancer mortality in
      the regions with contaminated water was more substantially elevated in comparison
      with the regions without contaminated water (1.82; 1.11-2.91) and the whole
      province (1.69; 1.12-2.44). Lung cancer mortality was slightly elevated in
      comparison with the unexposed study regions (1.15; 0.62-2.07), and more strongly
      elevated in comparison with the whole province (1.78; 1.03-2.87). Mortality from
      other cancers combined was not elevated in comparison with either the unexposed
      study regions (0.86; 0.53-1.36) or the whole province (0.92; 0.58-1.38).
      CONCLUSIONS: While these data are limited, they are consistent with increased
      stomach cancer risk in a population exposed to Crz=6 in drinking water.

PMID- 18091414
TI  - Hexavalent chromium, yellow water, and cancer: a convoluted saga.
AB  - In this issue, Beaumont et al report cancer mortality rates associated with
      exposure to high concentrations of hexavalent chromium in well water in Liaoning
      Province, China. Contamination of drinking water at these levels has been
      reported only once before, among a small group in Mexico. The investigation in
      China is a convoluted tale. The first report indicated an increase in cancer
      mortality, while a subsequent publication with the same lead author claimed no
      increased risks. In 2006, the journal publishing the latter paper retracted it
      because of failure to disclose financial and intellectual input to the paper by
      outside parties (linked to chromium polluting industries). Beaumont and his
      colleagues now provide a further reanalysis of these data, showing increased
      mortality in particular from stomach cancer, but with serious limitations in the
      data and methods of analysis. These limitations are counterbalanced by the
      importance of a study of perhaps the highest exposure to hexavalent chromium in
      water that will ever be experienced by a population large enough to estimate
      risks of cancer.

PMID- 18091415
TI  - Ending the cardiovascular disease epidemic: an interview with Lewis Kuller.
      Interviewed by Samuel S. Gidding.

PMID- 18091417
TI  - Hospitalizations in adolescence and early adulthood among Swedish men and women
      born preterm or small for gestational age.
AB  - BACKGROUND: Preterm birth and reduced intrauterine growth appear to be related to
      morbidity in childhood and later adulthood. We studied whether the risk of all
      cause hospitalization in adolescence and early adulthood differed between
      individuals who were born preterm or small for gestational age (SGA) compared
      with those born at term and appropriate for gestational age. METHODS: Using
      Swedish registries, we followed 304,275 men and women born in 1973-1975 for any
      hospitalizations occurring in 1987-1996. Preterm birth was defined as <37 weeks
      of gestation and SGA as babies smaller than 2 standard deviations below the mean
      weight for gestational length, according to Swedish standards. We created 3
      mutually exclusive categories: "preterm" (<37 weeks and not SGA), "SGA" (SGA and
      not preterm), and "both preterm and SGA." The comparison group was all term
      births not SGA. Childhood socioeconomic characteristics were accounted for in the
      analyses. RESULTS: The overall risk of hospitalization was higher for men and
      women born SGA (adjusted odds ratio = 1.16; 95% confidence interval = 1.12-1.21),
      for those born preterm (1.06; 1.02-1.10), and for those born both preterm and SGA
      (1.42; 1.26-1.59). In addition to higher risks for previously reported adverse
      health outcomes, such as neurodevelopment sequelae and congenital anomalies, men
      and women born SGA or preterm were more likely to be hospitalized due to
      unspecified symptoms. SGA also appeared to be associated with genitourinary
      diseases and drug use. CONCLUSIONS: Men and women born SGA or preterm were at
      higher risk for hospitalization during adolescence and early adulthood, with men
      and women born SGA more at risk than those born preterm.

PMID- 18091416
TI  - Body size and blood pressure: an analysis of Africans and the African diaspora.
AB  - BACKGROUND: Blood pressure is directly and causally associated with body mass
      index (BMI) in populations worldwide. However, the relationship may vary across
      BMI in populations of African origin. METHODS: We compared the relationship
      between blood pressure and BMI in populations of African origin, using 13 samples
      from Africa, the Caribbean, the United Kingdom and the United States. We had
      access to data from individual participants for age, height, weight, blood
      pressure, and treatment of hypertension. Analysis was restricted to 18,072
      participants (age 35-64 years; 44% men). We carried out multivariate regression
      analysis to estimate the relationship between blood pressure and BMI by country
      and by sex. The use of antihypertensive treatment was taken into account by
      exclusion and by sensitivity analysis. RESULTS: There was a positive relationship
      between both systolic and diastolic blood pressure and BMI. In men the slopes for
      systolic blood pressure varied from 0.27 mm Hg per kg/m (95% confidence interval
      = -0.01 to 0.56) in the United States to 1.72 mm Hg per kg/m (95% confidence
      interval = 0.92 to 2.53) in Ghana (Kumasi). In women, the slopes varied from 0.08
      (-0.54 to 0.72) in South Africa to 1.32 (0.98 to 1.66) in the Republic of Congo.
      Similar variation in trends was seen for diastolic blood pressure. The higher the
      BMI, the shallower the slopes [-0.10 (-0.15 to -0.06) for systolic, -0.09 (-0.12
      to -0.06) for diastolic]. No differences were seen after excluding persons who
      were being treated for hypertension. CONCLUSIONS: Blood pressure and BMI levels
      vary among populations of the African diaspora. The effect of BMI on blood
      pressure levels diminishes as BMI increases. These results suggest a complex
      relationship among excess body weight, adiposity, and energy expenditure.

PMID- 18091418
TI  - Estimating interaction between genetic and environmental risk factors: efficiency
      of sampling designs within a cohort.
AB  - Large prospective cohorts originally assembled to study environmental risk
      factors are increasingly exploited to study gene-environment interactions. Given
      the cost of genetic studies in large samples, being able to select a subsample
      for genotyping that contains most of the information from the cohort would lead
      to substantial savings. We consider nested case-control and case-cohort sampling
      designs with and without stratification and compare their efficiency relative to
      the entire cohort for estimating the effects of genetic and environmental risk
      factors and their interactions. Asymptotic calculations show that the relative
      efficiency of the case-cohort and nested case-control designs implementing the
      same sampling stratification are similar over a range of scenarios for the
      relationships among genes, environmental exposures, and disease status. Sampling
      equal numbers of exposed and unexposed subjects improves efficiency when the
      exposure is rare. The case-cohort designs had a slight advantage in simulations
      of sampling designs within the Framingham Offspring Study, using the interaction
      between apolipoprotein E and smoking on the risk of coronary heart disease as an
      example. It was possible to estimate the interaction effect with precision close
      to that of the full cohort when using case-cohort or nested case-control samples
      containing fewer than half the subjects of the cohort.

PMID- 18091419
TI  - The Breslow estimator of the nonparametric baseline survivor function in Cox's
      regression model: some heuristics.
AB  - Most survival analysis textbooks explain how the hazard ratio parameters in Cox's
      life table regression model are estimated. Fewer explain how the components of
      the nonparametric baseline survivor function are derived. Those that do often
      relegate the explanation to an "advanced" section and merely present the
      components as algebraic or iterative solutions to estimating equations. None
      comment on the structure of these estimators. This note brings out a heuristic
      representation that may help to de-mystify the structure.

PMID- 18091420
TI  - The effect of rainfall on the incidence of cholera in Bangladesh.
AB  - BACKGROUND: The incidence of cholera in Bangladesh shows clear seasonality,
      suggesting that weather factors could play a role in its epidemiology. We
      estimated the effects of rainfall on the incidence of cholera in Dhaka,
      Bangladesh. METHODS: We examined time-series patterns of the weekly number of
      hospital visits due to cholera in relation to weekly rainfall from 1996 to 2002.
      We used Poisson regression models, adjusted for seasonal variation, between-year
      variation, public holidays, and temperature. The role of river level on the
      rainfall-cholera relationship was also examined by incorporating river-level
      terms into the models. RESULTS: The weekly number of cholera cases increased by
      14% (95% confidence interval = 10.1%-18.9%) for each 10-mm increase above the
      threshold of 45 mm for the average rainfall, over lags 0 to 8 weeks. Conversely,
      the number of cholera cases increased by 24% (10.7%-38.6%) for a 10-mm decrease
      below the same threshold of average rainfall, over lags 0 to 16 weeks. River
      level partly explained the association between high rainfall and the number of
      cholera cases. CONCLUSIONS: The number of cholera cases increased with both high
      and low rainfall in the weeks preceding hospital visits. These results suggest
      that factors associated with river level are on the causal pathway between high
      rainfall and incidence of cholera.

PMID- 18091421
TI  - Traffic-related air pollution in relation to incidence and prognosis of coronary
      heart disease.
AB  - BACKGROUND: Long-term air pollution exposure is associated with increased
      mortality, but the association with incidence of fatal and nonfatal coronary
      heart disease is less certain. Moreover, it is unknown how chronic exposure to
      air pollution affects prognosis among survivors of a first coronary event. This
      study evaluated the association between long-term traffic-related air pollution
      exposure and incidence of nonfatal and fatal coronary events, as well as
      subsequent hospital readmission and mortality among myocardial infarction
      survivors. METHODS: The study population comprised all residents of Rome aged 35
      84 years during the period 1998-2000. Residential nitrogen dioxide (NO2) exposure
      as a marker of traffic pollution was assessed by a land-use regression model in
      1995-1996 (R = 0.69). A total of 11,167 incident coronary events were observed
      (4654 fatal, including 3598 out-of-hospital coronary deaths, and 6513 nonfatal).
      The cohort of 6513 survivors was followed 4.0-7.5 years for readmission or
      mortality, starting 28 days from the date of first event. Relative risks per 10
      mug/m of NO2 exposure, adjusted for age, sex, and socioeconomic status, were
      calculated by Poisson regression (population-based incidence) and Cox regression
      (cohort analysis). RESULTS: The relative risk for incidence in coronary events
      per 10 mug/m of NO2 was 1.03 (95% confidence interval = 1.00-1.07). Stronger
      associations were found for fatal cases (1.07; 1.02-1.12) and out-of-hospital
      deaths (1.08; 1.02-1.13). Using NO2 exposure at the time of the first event,
      there was no association of air pollution exposure with either subsequent
      hospital readmission or mortality among survivors of the first coronary event.
      CONCLUSIONS: Long-term air pollution exposure increases the risk of coronary
      heart disease, particularly fatal events. Hospital readmission or subsequent
      mortality among survivors was not associated with traffic air pollution.

PMID- 18091422
TI  - Characterizing temperature and mortality in nine California counties.
AB  - BACKGROUND: Elevated temperature has been associated with increased mortality.
      Few epidemiologic studies, however, have considered air pollutants as potential
      confounders or effect modifiers. None has focused on California, where the
      climate is generally mild and pollution levels tend to be high-an ideal setting
      to examine the independent effect of temperature from air pollution. METHODS: We
      examined the association between mean daily apparent temperature and
      nonaccidental mortality in 9 counties throughout California from May to September
      1999-2003. Data were obtained from the National Climatic Data Center (temperature
      and relative humidity), the California Department of Health Services (mortality),
      and the California Air Resources Board (particulate matter, ozone, carbon
      monoxide, and nitrogen dioxide). We conducted a time-stratified case-crossover
      study, with a time-series analysis as a sensitivity analysis, adjusting for day
      of the week using both methods and adjusting for time trend in the time-series
      analysis. We first obtained county-specific estimates and then combined them
      using meta-analytic methods. RESULTS: A total of 248,019 deaths were included.
      Each 10 degrees (Fahrenheit) increase in same-day mean apparent temperature
      corresponded to a 2.3% increase in mortality (95% confidence interval = 1.0%
      3.6%) in the case-crossover analysis for all 9 counties combined, with nearly
      identical results produced from the time-series analysis. No air pollutant
      examined was found to be a significant confounder or effect modifier.
      CONCLUSIONS: Even without extremes in apparent temperature, we observed an
      association between temperature and mortality in California that was independent
      of air pollution.

PMID- 18091423
TI  - Seven deadly sins of environmental epidemiology and the virtues of precaution.
AB  - The potentials for error in planning, conducting, reporting, and utilizing
      epidemiologic results can be considered in terms of the traditional 7 deadly
      sins. To counter these sins, epidemiologic virtues should be inspired by the
      precautionary principle. The remedies emphasize acknowledgment and exploration of
      the impact of uncertainties, weight-of-the-evidence assessments that consider
      what could be known given the opportunities for research, and epidemiologic
      strategies that facilitate the use of tentative, though innovative, studies in
      decision-making.

PMID- 18091424
TI  - The Johnstown flood: an unnatural disaster.

PMID- 18091426
TI  - Soy formula and breast cancer risk.

PMID- 18091427
TI  - Car air fresheners as a source of ethnic differences in exposure to 1,4
      dichlorobenzene.

PMID- 18091428
TI  - Evidence based medicine meets genomic medicine.

PMID- 18091429
TI  - Genetics of Parkinson disease.
AB  - During the past decade five genes have been identified that are important in
      autosomal dominant and autosomal recessive forms of Parkinson disease. The
      identification of these genes has increased our understanding of the likely
      pathogenic mechanisms resulting in disease. However, mutations in these genes
      likely contribute to disease in fewer than 5% of all cases of Parkinson disease.
      Thus, researchers have continued to search for genes that may influence disease
      susceptibility. Molecular diagnostic testing is currently available for four of
      the genes mutated in Parkinson disease. Evidence for reduced penetrance, possible
      effects of haploinsufficiency, and the identification of nondisease causing
      polymorphisms within several of these genes has made genetic counseling
      challenging. Current recommendations are to limit molecular testing only to those
      individuals who are symptomatic. Furthermore, because treatment is unaltered by
      the presence or absence of mutations in these genes, restraint is recommended
      when considering the value of screening for mutations in a clinical setting.

PMID- 18091430
TI  - Osteopenia: a common aspect of Fabry disease. Predictors of bone mineral density.
AB  - PURPOSE: We investigated the bone mineral status in patients with untreated Fabry
      disease (FD). METHODS: Descriptive, cross-sectional study in 53 patients with FD
      investigating bone mineral density (BMD)/content (dual energy x-ray
      absorptiometry scan), bone metabolism (parathyroid hormone, osteocalcin, and
      insulin-like growth factor I), and renal function (ethylene diamine tetraacetic
      acid clearance). RESULTS: Mean BMD z score at the lumbar spine and femoral neck
      were -0.05 +/- 1.46 SD and -0.37 +/- 1.02 SD, respectively. Approximately 50% had
      osteopenia in the hip or lumbar spine and additionally four had osteoporosis.
      Multivariate analysis including body weight, impaired renal function, and
      genotype overall explained 48% of the variance in lumbar spine BMD (P < 0.001),
      whereas body weight, impaired renal function, and menopausal status in the female
      population accounted for more than 50% of the variation in BMD of both the lumbar
      spine and femoral neck (both P < 0.001). Twenty percent of patients had
      hyperparathyroidism. Although the level of parathyroid hormone was significantly
      associated with impaired renal function, osteocalcin levels were significantly
      higher in patients with lumbar spine osteopenia or osteoporosis than in those
      with normal BMD. CONCLUSIONS: Osteopenia was present in approximately 50% of
      patients with untreated FD. Whether BMD and bone metabolism will improve after
      enzyme replacement therapy remains to be established.

PMID- 18091431
TI  - Recommendations from the EGAPP Working Group: testing for cytochrome P450
      polymorphisms in adults with nonpsychotic depression treated with selective
      serotonin reuptake inhibitors.
AB  - This statement summarizes the Evaluation of Genomic Applications in Practice and
      Prevention (EGAPP) Working Group recommendations regarding CYP450 genetic testing
      in adult patients beginning treatment with selective serotonin reuptake
      inhibitors (SSRIs), and the supporting scientific evidence. EGAPP is a project
      developed by the National Office of Public Health Genomics at the Centers for
      Disease Control and Prevention to support a rigorous, evidence-based process for
      evaluating genetic tests and other genomic applications that are in transition
      from research to clinical and public health practice in the United States. A key
      goal of the EGAPP Working Group is to develop conclusions and recommendations
      regarding clinical genomic applications and to establish clear linkage to the
      supporting scientific evidence. The Working Group members are nonfederal experts
      in genetics, laboratory medicine, and clinical epidemiology convened to establish
      methods and processes; set priorities for review topics; participate in technical
      expert panels for commissioned evidence reviews; publish recommendations; and
      provide guidance and feedback on other project activities. SUMMARY OF
      RECOMMENDATION: The EGAPP Working Group found insufficient evidence to support a
      recommendation for or against use of CYP450 testing in adults beginning SSRI
      treatment for non-psychotic depression. In the absence of supporting evidence,
      and with consideration of other contextual issues, EGAPP discourages use of
      CYP450 testing for patients beginning SSRI treatment until further clinical
      trials are completed. RATIONALE: The EGAPP Working Group found no evidence
      linking testing for CYP450 to clinical outcomes in adults treated with SSRIs.
      While some studies of a single SSRI dose in healthy patients report an
      association between genotypic CYP450 drug metabolizer status and circulating SSRI
      levels, this association was not supported by studies of patients receiving
      ongoing SSRI treatment. Further, CYP450 genotypes are not consistently associated
      with the patient outcomes of interest, including clinical response to SSRI
      treatment or adverse events as a result of treatment. No evidence was available
      showing that the results of CYP450 testing influenced SSRI choice or dose and
      improved patient outcomes, or was useful in medical, personal, or public health
      decision-making. In the absence of evidence supporting clinical utility, it is
      not known if potential benefits from CYP450 testing will outweigh potential
      harms. Potential harms may include increased cost without impact on clinical
      decision making or improvement in patient outcomes, less effective treatment with
      SSRI drugs, or inappropriate use of genotype information in the management of
      other drugs metabolized by CYP450 enzymes.

PMID- 18091432
TI  - Review of evidence for genetic testing for CYP450 polymorphisms in management of
      patients with nonpsychotic depression with selective serotonin reuptake
      inhibitors.
AB  - PURPOSE: Cytochrome P450 (CYP450) enzymes metabolize selective serotonin reuptake
      inhibitor (SSRI) drugs used in treatment of depression. Variants in these genes
      may impact treatment efficacy and tolerability. The purpose of this study was 2
      fold: to systematically review the literature for evidence supporting CYP450
      genotyping to guide SSRI treatment for major depression, and, where evidence is
      inadequate, to suggest future research. METHODS: We searched MEDLINE(R) and other
      databases for studies addressing five key questions suggested by the Evaluation
      of Genomic Applications in Practice and Prevention Working Group. Eligibility
      criteria were defined, and studies were reviewed independently by paired
      researchers. A conceptual model was developed to guide future research. RESULTS:
      Review of 1200 abstracts led to the final inclusion of 37 articles. The evidence
      indicates relatively high analytic sensitivity and specificity of tests detecting
      a subset of polymorphisms of CYP2D6, 2C19, 2C8, 2C9, and 1A1. We found marginal
      evidence regarding a clinical association between CYP450 variants and SSRI
      metabolism, efficacy, and tolerability in the treatment of depression.
      CONCLUSIONS: Current evidence does not support the use of CYP450 genotyping to
      guide SSRI treatment of patients with depression. Studies are proposed that will
      effectively guide decision-making in the area of CYP450 testing in depression,
      and genetic testing more generally.

PMID- 18091433
TI  - Heterogeneous molecular mechanisms underlie attenuated familial adenomatous
      polyposis.
AB  - PURPOSE: Familial adenomatous polyposis is a phenotypically heterogeneous disease
      predisposing to colorectal cancer. It is dominantly transmitted, when associated
      with the APC gene, and recessively inherited, when associated with MUTYH gene. We
      searched for APC and MUTYH germline alterations in Italian and Greek patients
      with attenuated polyposis, a phenotypic variant whose genetic cause remains
      unknown in many cases. METHODS: We studied 26 unrelated patients (and 16
      relatives) with multiple colorectal adenomas (3-100, by endoscopic analysis) that
      had screened APC mutation-negative by protein truncation test. We searched for
      APC rearrangements by multiplex ligation-dependent probe amplification and for
      MUTYH mutations by sequencing. We performed a screening of five MUTYH recurrent
      pathogenic mutations in 501 Italian and 144 Greek controls. RESULTS: One patient
      proved to carry an APC whole-gene deletion; 4 of 25 (16%) patients showed
      biallelic and 3 of 25 (12%) monoallelic MUTYH mutations. In the three
      heterozygous subjects no pathogenetic variants were found in OGG1, MTH1, APE1,
      MSH2, and MSH6 genes. Frequency assessment of MUTYH mutations in healthy subjects
      showed that only Y165C and G382D reach a subpolymorphic frequency. CONCLUSION:
      Attenuated polyposis patients without "conventional" APC mutations are
      genetically heterogeneous, and the phenotype is not directly related to the
      germline defect. Therefore, the families' appropriate management requires an
      accurate genetic and clinical investigation.

PMID- 18091434
TI  - Primary care physicians' concerns about offering a genetic test to tailor smoking
      cessation treatment.
AB  - PURPOSE: We assessed the importance assigned by primary care physicians to eight
      factors influencing whether they would order a genetic test to individually
      tailor smoking cessation treatment. METHODS: A random sample of United States
      primary care physicians was surveyed about how important each of eight factors
      were in the decision to order the test. Broadly, these factors included the
      ability of the test to improve treatment, the patient's reaction to test results,
      concern about misuse of test results, and the ability of the physician's office
      to manage informed consent for the test. RESULTS: Physicians indicated the most
      important factor they would consider in ordering a genetic test to tailor smoking
      cessation treatment was the ability to improve cessation outcomes. However, when
      told the genotype identified by the test was associated with stigma-inducing
      mental health conditions, physicians emphasized the importance of possible
      racial, insurance, and employment discrimination in their decisions. CONCLUSIONS:
      Primary care physicians are eager to improve smoking cessation treatment, but the
      collateral information generated by genetic testing to tailor treatment may be an
      impediment unless proper antidiscrimination measures are in place.

PMID- 18091435
TI  - Myriad and the mass media: the covering of a gene patent controversy.
AB  - PURPOSE: We explore how the print media in four jurisdictions framed the
      controversy surrounding Myriad Genetic's BRCA patents and consider the possible
      influence of media on public perceptions and policy reform. METHOD: We used a
      broad search strategy to collect newspaper articles from Factiva and Lexis/Nexis
      on Myriad Genetics and the BRCA gene and identified the main triggers for those
      articles. We then selected articles on the BRCA gene patents for coding. The
      coding frame queried the presence or absence of either positive or negative
      statements about gene patenting and a subjective assessment of the tone of the
      article. We compared the differences in tone and number of positive and negative
      statements between jurisdictions (Australia, Canada, United Kingdom, and United
      States). RESULTS: Myriad Genetic's BRCA1/2 gene patents sparked significant
      international newspaper coverage in comparison to other stories on gene patenting
      controversies. Only 55.9% of 143 articles presented a variety of perspectives.
      The majority of articles (77.6%) had a negative overall tenor; only 6.29% had a
      positive overall tenor, whereas 16.1% were neutral. There were significant
      differences in the overall tenor between jurisdictions, with Canadian coverage
      being overwhelmingly negative in comparison with the other three jurisdictions.
      The main triggers for news coverage were largely local licensing deals, actions
      at regional patent offices, and statements and publications by prominent figures.
      CONCLUSION: Myriad's patents were largely portrayed as a negative story, except
      in Utah where Myriad Genetics is located, and as an example of the problems
      associated with gene patents. The story was primarily framed as a social dilemma
      that needed to be addressed. In Canada there was a disproportionate level of
      coverage of the political response to the threat of patent infringement action
      against government testing laboratories and potential impacts on public health
      care. In Europe and elsewhere in the United States, the opposition to gene
      patenting at the European Patent Office predominated. In these contexts, our data
      provide some support that the media coverage helped to drive the policy agenda,
      although the resultant policy response received almost no media attention.

PMID- 18091437
TI  - Diagnosis, counseling, and gender assignment.

PMID- 18091439
TI  - Work-arounds in health care settings: Literature review and research agenda.
AB  - BACKGROUND: As health care professionals seek to balance technological and
      regulatory demands with the need to provide patient-centered care, all in an
      efficient and cost-effective manner, they may see a greater need to improvise or
      work around intended work practices. Health care professionals acknowledge
      widespread use of work-arounds, and the literature documents their prevalence and
      influence on performance. Despite their importance, few studies have focused
      exclusively on work-arounds. This suggests a key area of need in the research,
      particularly because work-arounds are frequently cited in the context of serious
      patient safety consequences. PURPOSE: The purpose of this article is to review
      the existing literature concerning work-arounds to elucidate the definition and
      nature of work-arounds, how work-arounds can be differentiated from similar
      constructs (e.g., errors, mistakes, and deviance), and the potential causes of
      work-arounds and to explore potential consequences of work-arounds in health care
      settings. APPROACH: We conducted a systematic review of the literature concerning
      work-arounds to develop themes concerning the nature of work-arounds and ideas
      for future research on the topic. IMPLICATIONS FOR PRACTICE: In this article, we
      develop links between work-arounds and potential outcomes, particularly safety
      outcomes. Moreover, we discuss the manner in which open discussion can allow work
      arounds to facilitate work process improvement and the role that climate and
      culture play in reducing work-arounds.

PMID- 18091440
TI  - The impact of health system membership on patient safety initiatives.
AB  - BACKGROUND: Research in configurations and strategic groups has a rich history of
      revealing performance differences for hospitals and health care systems.
      PURPOSES: To assess the relationship between hospital-led health system
      configurations and the adoption of patient safety practices. In particular, the
      adoption of computerized physician order entry (CPOE) and intensive care unit
      physician staffing (IPS) is analyzed. METHODOLOGY: Analysis of variance was used
      to detect differences in patient safety measures based on health networks and
      systems' initial configuration clustering, and regression was used to assess
      group membership, controlling for hospital-level characteristics. The 2002
      American Hospital Association survey and the first 3 years of the Leapfrog Group
      annual survey (2003-2005) are used for the analyses. RESULTS: There were
      significant differences in CPOE and IPS adoption and implementation levels based
      on health systems' configurations. Centralized physician/insurance health systems
      and moderately centralized health systems were the highest configurations in
      terms of CPOE adoption. Group membership was not positively related to the use of
      IPS relative to hospitals that are not classified using the taxonomy. In fact,
      there is a significant and negative adoption rate for both patient safety
      measures in facilities classified in the independent hospital systems category.
      CONCLUSION: There are systematic differences in the adoption of CPOE and IPS
      patient safety measures based on health system configurations. The configuration
      with an insurance company as part of its structure was more likely than other
      groups to be adopting CPOE. PRACTITIONER IMPLICATIONS: Given the durability of
      group membership, the Leapfrog Group and other patient safety initiatives could
      explicitly target configurations most likely to adopt and implement patient
      safety programs.

PMID- 18091441
TI  - Family medicine practice performance and knowledge management.
AB  - BACKGROUND: Knowledge management (KM) is the process by which people in
      organizations find, share, and develop knowledge for action. KM affects
      performance by influencing work relationships to enhance learning and decision
      making. PURPOSE: To identify how family medicine practices exhibit KM.
      METHODOLOGY: A model and a template of KM concepts were derived from a
      comprehensive organizational literature review. Two higher and two lower
      performing family medicine practices were purposefully selected from existing
      comparative case studies based on prevention delivery rates and innovation.
      Interviews, fieldnotes of operations, and clinical encounters were coded
      independently using the template. Face-to-face discussions resolved coding
      differences. FINDINGS: All practices had processes and tools for finding,
      sharing, and developing knowledge; however, KM overall was limited despite
      implementation of expensive technologies like an electronic medical record. Where
      present, KM processes and tools were used by individuals but not integrated
      throughout the organization. Loss of information was prominent, and finding
      knowledge was underdeveloped. The use of technical tools and developing knowledge
      by reconfiguration and measurement were particularly limited. Socially related
      tools, such as face-to-face-communication for sharing and developing knowledge,
      were more developed. As in other organizations, tool use was tailored for
      specific outcomes and leveraged by other organizational capacities. PRACTICE
      IMPLICATIONS: Differences in KM occur within family practices and between family
      practices and other organizations and may have implications for improving
      practice performance. Understanding interaction patterns of work relationships
      and KM may explain why costly technical or externally imposed "one size fits all"
      practice organizational interventions have had mixed results and limited
      sustainability.

PMID- 18091442
TI  - Linking physician burnout and patient outcomes: exploring the dyadic relationship
      between physicians and patients.
AB  - BACKGROUND: Although patient outcomes of hospital stays have been widely
      explored, particularly patient satisfaction, there is a dearth of research
      linking health care provider burnout and patient outcomes at a dyadic level. In
      this article, we develop and test a model to explain the relationship between
      dimensions of burnout and patient outcomes, including patient satisfaction and
      recovery time. PURPOSE: The purpose of this article is to explore the
      relationship between physician burnout and patient satisfaction and the time
      required to regain normal functioning after hospital discharge. METHODS: This
      study was based upon a survey of 178 matched pairs of patients and physicians.
      The patients were people who had been hospitalized within the previous year.
      RESULTS: We found support for the notion that the depersonalization dimension of
      physician burnout was associated with patient outcomes of lower satisfaction and
      longer post discharge recovery time (after controlling for severity of illness
      and other demographic factors). IMPLICATIONS FOR PRACTICE: The findings suggest
      that physician burnout has an impact on patient outcomes. Although this is a
      preliminary study, it suggests that organizations that take proactive steps to
      reduce burnout through system wide intervention programs will see greater
      benefits in terms of patient satisfaction and recovery.

PMID- 18091443
TI  - Career stress and female managers' health in Taiwan's hospitals: a multilevel
      model approach.
AB  - PURPOSE: This study investigates how perception-induced stress (barrier) and
      social capital (facilitator) affect the health of female managers. METHODS AND
      MEASUREMENT: On the basis of the responses of 229 valid questionnaires of middle-
      and high-level female managers in large-scale hospitals, using a multilevel data
      analysis approach, this study investigates how perception-induced stress and
      social capital influence self-reported poor health of female managers. RESULTS:
      Analysis results indicate that all 3 perception-induced stresses (i.e., promotion
      related procedural justice, promotion rate, and work-family conflict) and 2
      social capital variables (i.e., mentor-assisted promotion and higher ranking
      mentor in other departments) are significantly associated with the health of
      female mangers. Factors involving the career success of women also affect their
      health. IMPLICATIONS AND CONCLUSIONS: Health care organizations expecting to
      benefit from the long-term contribution of female elites must promote
      organizational equity and more heavily emphasize flexible work schedules, family
      friendly policies, and perception management practices. In addition, adequately
      designed mentorship practices can greatly benefit female managers.

PMID- 18091444
TI  - Hospital quality of care: does information technology matter? The relationship
      between information technology adoption and quality of care.
AB  - BACKGROUND: Hospitals have been slow to adopt information technology (IT) largely
      because of a lack of generalizable evidence of the value associated with such
      adoption. PURPOSE: To explore the relationship between IT adoption and quality of
      care in acute-care hospitals. METHODS: Primary data on hospital IT adoption were
      combined with secondary hospital discharge data. Regression analyses were used to
      examine the relationship between various measures of IT adoption and several
      quality indicators after controlling for confounders. Adoption of IT was measured
      using a previously validated method that considers clinical, administrative, and
      strategic IT capabilities of acute-care hospitals. Quality measures included the
      Inpatient Quality Indicators developed by the Agency for Healthcare Research and
      Quality. RESULTS: Data from 98 hospitals were available for analyses. Hospitals
      adopted an average of 11.3 (45.2%) clinical IT applications, 15.7 (74.8%)
      administrative IT applications, and 5 (50%) strategic IT applications. In
      multivariate regression analyses, hospitals that adopted a greater number of IT
      applications were significantly more likely to have desirable quality outcomes on
      seven Inpatient Quality Indicator measures, including risk-adjusted mortality
      from percutaneous transluminal coronary angioplasty, gastrointestinal hemorrhage,
      and acute myocardial infarction. An increase in clinical IT applications was also
      inversely correlated with utilization of incidental appendectomy, and an increase
      in the adoption of strategic IT applications was inversely correlated with risk
      adjusted mortality from craniotomy and laparoscopic cholecystectomy. PRACTICE
      IMPLICATIONS: Hospital adoption of IT is associated with desirable quality
      outcomes across hospitals in Florida. These findings will assist hospital leaders
      interested in understanding better the effect of costly IT adoption on quality of
      care in their institutions.

PMID- 18091445
TI  - The effect of information technology investment on firm-level performance in the
      health care industry.
AB  - BACKGROUND: The return on investment for information technology (IT) has been the
      subject of much debate throughout the history of management information systems
      research. Often referred to as the productivity paradox, increased IT investments
      have not been consistently associated with increased productivity. Understanding
      individual IT factors that directly contribute to business value should provide
      insight into the productivity paradox. PURPOSE: The effects of 3 different firm
      level IT characteristics on financial performance in the health care industry are
      studied. Specifically, the effects of IT budget, IT outsourcing, and the relative
      number of IT personnel on firm-level financial performance are analyzed. METHODS:
      Regression analysis of archival survey data for 914 Integrated Healthcare
      Delivery Systems is performed. RESULTS: IT budgetary expenditures and the number
      of IT services outsourced are associated with increases in the profitability of
      Integrated Healthcare Delivery Systems, whereas increases in IT personnel are not
      significantly associated with increased profitability. Each one tenth of a
      percentage increase in IT expenditures is associated with approximately $100,000
      in increased profit, and each additional IT service outsourced is associated with
      approximately $950,000 in increased profit for an average-sized Integrated
      Healthcare Delivery System. IMPLICATIONS: To increase profitability, IT
      administrators should increase IT budgetary expenditures along with IT
      outsourcing levels. IT administrators in the health care industry can use such
      findings during budgeting cycles to justify increased investments in IT personnel
      as being budget neutral while increasing organizational capacity.

PMID- 18091446
TI  - Turnover and vacancy rates for registered nurses: do local labor market factors
      matter?
AB  - BACKGROUND: Turnover of nursing staff is a significant issue affecting health
      care cost, quality, and access. In recent years, a worldwide shortage of skilled
      nurses has resulted in sharply higher vacancy rates for registered nurses in many
      health care organizations. Much research has focused on the individual, group,
      and organizational determinants of turnover. Labor market factors have also been
      suggested as important contributors to turnover and vacancy rates but have
      received limited attention by scholars. PURPOSE: This study proposes and tests a
      conceptual model showing the relationships of organization-market fit and three
      local labor market factors with organizational turnover and vacancy rates.
      METHODS: The model is tested using ordinary least squares regression with data
      collected from 713 Canadian hospitals and nursing homes. RESULTS: Results suggest
      that, although modest in their impact, labor market and the organization-market
      fit factors do make significant yet differential contributions to turnover and
      vacancy rates for registered nurses. IMPLICATIONS: Knowledge of labor market
      factors can substantially shape an effective campaign to recruit and retain
      nurses. This is particularly true for employers who are perceived to be
      "employers-of-choice."

PMID- 18091447
TI  - Special care units and their influence on nursing home occupancy characteristics.
AB  - BACKGROUND: There has been a steady increase in the number of special care units
      (SCUs) in nursing homes. In 2006, 4,370 (i.e., 29%) nursing homes reported having
      an SCU. One belief is that SCUs in nursing homes developed to provide better
      resident care. However, few studies have examined the impact of opening an SCU on
      the nursing home, rather than the impact on residents. PURPOSE: In this research,
      we use national data over a period of 15 years (1991-2006) to examine whether
      opening either an Alzheimer's SCU or subacute SCU subsequently influences the
      overall nursing home occupancy, Medicare occupancy, or private-pay occupancy.
      METHODOLOGY/APPROACH: The 1991 through 2006 On-line Survey Certification of
      Automated Records was the primary data source used in this investigation. Using
      multivariate regression, overall occupancy, Medicare occupancy, and private-pay
      occupancy variables were examined 1, 2, and 3 years prior to opening of an SCU
      and 1, 2, and 3 years postopening of an SCU. FINDINGS: Opening either an
      Alzheimer's SCU or subacute SCU had a positive impact on both the overall
      occupancy and private-pay occupancy of a facility. In addition, opening a
      subacute SCU had a positive impact on Medicare occupancy. These positive changes
      occur within a year of opening the SCU and increase each year thereafter.
      PRACTICE IMPLICATIONS: The improvements in occupancy and payer-mix identified
      could mean the difference between operating in the black as opposed to making a
      loss. Thus, the findings have substantial practice implications for nursing
      homes.

PMID- 18091448
TI  - Aqueous humor erythropoietin levels in patients with primary open-angle glaucoma.
AB  - PURPOSE: To evaluate the levels of erythropoietin (EPO) in the aqueous humor in
      eyes with primary open-angle glaucoma (POAG) and without glaucoma. METHODS:
      Levels of EPO were measured using a sandwich enzyme-linked immunosorbent assay
      kit in aqueous humor aspirates taken during anterior segment surgery from 45
      patients, of whom 20 had POAG and 25 had senile cataract only. RESULTS: The mean
      aqueous humor EPO concentration in eyes with POAG (10.91+/-4.32 mU/mL) was
      significantly higher than that from eyes with cataract (8.24+/-1.77 mU/mL,
      P=0.008). There was no significant difference between the serum EPO
      concentrations of POAG (26.46+/-10.36 mU/mL) and the control group (24.50+/-7.59
      mU/mL, P=0.468). There was no correlation (P=0.165) between the EPO aqueous humor
      concentration and the EPO serum concentration while there was no correlation
      between the EPO aqueous humor concentration and the EPO serum concentration in
      the control group (P=0.819). CONCLUSIONS: The aqueous humor EPO level is
      increased in eyes with POAG.

PMID- 18091449
TI  - Personality type of the glaucoma patient.
AB  - PURPOSE: To characterize the personality profile of glaucoma subjects. PATIENTS
      AND METHODS: One hundred eight subjects including 56 open-angle glaucoma (OAG)
      and 52 controls were given the Minnesota Multiphasic Personality Inventory-2
      (MMPI-2) test and all performed automated perimetry. Clinical and demographic
      information which could relate to personality type was collected. RESULTS: OAG
      subjects had significantly higher Hypochondriasis (Hs; P=0.0082), Hysteria (Hy;
      P=0.0056), and Health Concerns (HEA; P=0.0025) mean scores than the control
      group. OAG subjects also had a significantly greater frequency of clinically
      abnormal score for hysteria (P=0.0262), and health concerns (P=0.0018).
      Multivariate analysis of variance revealed that Hypochondriasis, Hysteria, and
      Health Concerns scores were related to number of systemic medications used and to
      diagnostic group. Other potential explanatory variables such as sex, ethnicity,
      number of medical problems, length of glaucoma diagnosis, occurrence of glaucoma
      surgery, intraocular pressure, and visual status (logMAR, visual field indices)
      were not related to these personality scores. CONCLUSIONS: Patients with a
      diagnosis of OAG had more abnormal MMPI-2 scores in areas that focus upon
      concerns of somatic complaints and poor health. The use of systemic medications,
      which may be a constant reminder of illness, is a factor that may contribute to
      higher MMPI-2 scores.

PMID- 18091450
TI  - Stratus OCT in dominant optic atrophy: features differentiating it from glaucoma.
AB  - PURPOSE: To describe the Stratus optical coherence tomography (OCT) retinal nerve
      fiber layer (RNFL) thickness profile of dominant optic atrophy (DOA), to
      differentiate it from that of glaucoma. METHODS: RNFL thickness was measured
      using Stratus OCT in 32 eyes of 16 DOA patients. RESULTS: The temporal-most clock
      hour measurement was outside the 95% normal limit in 29 of the 32 DOA eyes
      (90.6%). The pattern of RNFL damage was bilaterally symmetrical in location and
      severity in all subjects. CONCLUSION: Stratus OCT shows characteristic findings
      differentiating DOA from glaucoma.

PMID- 18091451
TI  - Preperimetric glaucoma assessment with scanning laser polarimetry (GDx VCC):
      analysis of retinal nerve fiber layer by sectors.
AB  - PURPOSE: To evaluate the capability of the GDx VCC nerve fiber analyzer to detect
      preperimetric glaucoma across 12 retinal nerve fiber layer (RNFL) peripapillary
      sectors. METHODS: Data were obtained in a cross-sectional, hospital clinic-based
      study; 699 eyes from 699 glaucoma suspects were enrolled in this protocol. All
      subjects underwent ophthalmologic examination, static automated perimetry
      [Humphrey 24-2 Swedish interactive threshold algorithm (SITA) Standard], optic
      nerve stereoscopic photographs, red-free digital RNFL photographs and GDx VCC
      examination. Group S included 283 normal eyes and 39 preperimetric glaucoma eyes
      with RNFL superior or diffuse defects in the fiber layer photographs. Group I
      included 324 normal subjects and 24 with preperimetric glaucoma eyes with RNFL
      inferior or diffuse defects in fiber layer photographs. RESULTS: Mean values of
      the area under the curve (AUC) for receiver operating characteristic analysis for
      inferior average (Inf Avg), temporal-superior-nasal-inferior temporal average
      (TSNIT Avg), superior average (Sup Avg), and the nerve fiber indicator were
      significantly less in the eyes with RNFL defects than the control group compared
      with the AUC for thickness at hour 12 and at hour 6 calculated from the RNFL
      sector density. The AUC for receiver operating characteristic analysis of the new
      parameters improved by 12% with respect to the best GDx VCC standard values.
      CONCLUSIONS: Our results confirm that the 12 sector divisions of the GDx VCC have
      better diagnostic reliability in preperimetric glaucoma, and are able to improve
      the discrimination capability between normal and early damaged RNFLs.

PMID- 18091452
TI  - Visual field quality control in the Ocular Hypertension Treatment Study (OHTS).
AB  - OBJECTIVE: To report the impact of visual field quality control (QC) procedures
      on the rates of visual field unreliability, test parameter errors, and visual
      field defects attributed to testing artifacts in the Ocular Hypertension
      Treatment Study (OHTS). METHODS: OHTS technicians were certified for perimetry
      and were required to submit 2 sets of visual fields that met study criteria
      before testing study participants. The OHTS Visual Field Reading Center (VFRC)
      evaluated 46,777 visual fields completed by 1618 OHTS participants between
      February 1994 and December 2003. Visual field QC errors, rates of unreliability,
      and defects attributed to testing artifacts were assessed. The OHTS QC system
      addressed 3 areas of clinic performance: (1) test parameter errors, (2) patient
      data errors, and (3) shipment errors. A visual field was classified as unreliable
      if any of the reliability indices exceeded the 33% limit. Clinical sites were
      immediately contacted by the VFRC via fax, e-mail, and/or phone and instructed on
      how to prevent further testing errors on fields with defects attributed to
      testing artifacts. MAIN OUTCOME MEASURES: QC errors (test parameter errors) and
      unreliability rates. RESULTS: A total of 2.4% (1136/ 46,777) of the visual fields
      were unreliable and 0.23% (107/46,777) had incorrect test parameters. Visual
      field defects attributed to testing artifacts occurred in approximately 1%
      (483/46,777) of the visual fields. CONCLUSIONS: Prompt transmission of visual
      fields to the VFRC for ongoing and intensive QC monitoring and rapid feedback to
      technicians helps to reduce the frequency of unreliable visual fields and
      incorrect testing parameters. Visual field defects attributed to testing
      artifacts were infrequent in the OHTS.

PMID- 18091453
TI  - The quality of reporting of diagnostic accuracy studies in glaucoma using
      scanning laser polarimetry.
AB  - PURPOSE: Scanning laser polarimetry (SLP) has been proposed as a useful
      diagnostic test for glaucoma. This study was conducted to evaluate the quality of
      reporting of published studies using the SLP for diagnosing glaucoma. METHODS: A
      validated Medline and hand search of English-language articles reporting on
      measures of diagnostic accuracy of the SLP for glaucoma was performed. Two
      reviewers independently selected and appraised the manuscripts. The Standards for
      Reporting of Diagnostic Accuracy (STARD) checklist was used to evaluate the
      quality of each publication. RESULTS: A total of 47 papers were identified of
      which the first 10 (from 1997 to 2000) and the last 10 articles (from 2004 to
      2005) were appraised. Interobserver rating agreement of STARD items was high
      (85.5% agreement, kappa=0.796). The number of STARD items properly reported
      ranged from 3/25 to 19/25. Only a quarter of studies (5/20) explicitly reported
      more than half of the STARD items. Important aspects of the methodology were
      often missing such as participant sampling (reported in 40% of manuscripts),
      masking of the readers of the index test and reference standard (reported in 20%
      of manuscripts), and estimation of uncertainty (eg, 95% confidence intervals,
      reported in 25% of manuscripts). There was a slight increase in the number of
      STARD items reported with time. CONCLUSIONS: The quality of reporting of
      diagnostic accuracy tests for glaucoma with SLP is suboptimal. The STARD
      initiative may be a useful tool for appraising the strengths and weaknesses of
      diagnostic accuracy studies.

PMID- 18091454
TI  - The impact of the perimetric measurement scale, sample composition, and
      statistical method on the structure-function relationship in glaucoma.
AB  - PURPOSE: To investigate the impact of perimetric measurement scales, sample
      composition, and 2 statistical methods on the structure-function relationship in
      glaucoma. METHODS: Three hundred eighty-five eyes of 385 participants, covering
      the full spectrum of the disease from healthy to advanced glaucoma, were tested
      with the Heidelberg Retina Tomograph and standard automated perimetry (Swedish
      Interactive Thresholding Algorithm) within a 6-month period. The associations (R)
      between neuroretinal rim area and perimetric data expressed in logarithmic (dB)
      and linear (1/Lambert) units were measured for linear and curvilinear (quadratic
      and logarithmic) models. The best-fit model resulting from 2 statistical analyses
      (chi coefficient and analysis of the residuals) were compared in the visual field
      areas corresponding to the 6 Heidelberg Retina Tomograph sectors and in the
      central visual field. These analyses were performed on the complete sample and on
      a subset of the study population composed only of healthy controls and patients
      with definite glaucoma. RESULTS: The R values ranged from 0.01 to 0.32 with the
      strongest associations in the supero-temporal and infero-temporal optic disc
      regions. When perimetric data were expressed in dB units, the curvilinear models
      generally explained more variance than the linear model. When perimetric data
      were expressed in 1/Lambert units, differences were observed between the 2
      statistical and subgroup analyses. CONCLUSIONS: The perimetric measurement scale
      is one of many factors influencing the structure-function relationship. It is
      also influenced by the composition of the sample and by the statistical method of
      analysis. Expressing perimetric data in linear units does not always translate
      into linear structure-function relationships.

PMID- 18091455
TI  - Incidence and risk factors in secondary glaucomas after blunt and penetrating
      ocular trauma.
AB  - PURPOSE: This retrospective study was designed to evaluate the risk factors for
      the development of posttraumatic glaucoma after ocular trauma. METHODS: Data were
      obtained from the records of 102 patients (105 eyes) that experienced blunt or
      penetrating ocular trauma and presented to our center between January 1987 and
      April 2006. Logistic regression was used to evaluate the association between the
      baseline structural and functional ocular characteristics and posttraumatic
      glaucoma. Odds ratios with 95% confidence intervals (CI) were obtained. RESULTS:
      Need for glaucoma surgery was independently associated with hyphema (odds ratio:
      0.279; 95% CI: 0.085-0.916), corneal injury (odds ratio: 12.143; 95% CI: 2.029
      72.66), presence of optic atrophy (odds ratio: 8.000; 95% CI: 1.615-39.636),
      visual acuity <20/200 (odds ratio: 50.00; 95% CI: 10.183-245.501), and a history
      of penetrating ocular trauma (odds ratio: 10.00; 95% CI: 2.819-38.635). Corneal
      (odds ratio: 1.113; 95% CI: 1.022-1.213) and vitreal injuries (odds ratio:
      10.410; 95% CI: 1.232-87.97) were found to be statistically significant factors
      for the development of early glaucoma. CONCLUSIONS: This study found several
      independent predictive factors that were significantly associated with the need
      for glaucoma surgery in cases of posttraumatic glaucoma, including hyphema,
      corneal injury, presence of optic atrophy, visual acuity <20/200, and a history
      of penetrating ocular trauma. Additionally, some factors were found to affect the
      development of early glaucoma after ocular trauma, such as corneal and vitreal
      injury.

PMID- 18091456
TI  - Choroidal drainage in the management of acute angle closure after topiramate
      toxicity.
AB  - PURPOSE: To report the role of choroidal drainage in patient with acute bilateral
      angle closure secondary to cilio-choroidal effusion with Topiramate. DESIGN:
      Interventional case report. METHODS: Two weeks after commencing tablet Topiramate
      (Sulfamate derivative) for management of epilepsy, a patient developed bilateral
      acute angle closure secondary to cilio-choroidal effusion with lenticulo-corneal
      touches for which choroidal drainage was performed in 1 eye. RESULTS: After
      choroidal drainage, anterior chamber deepened, corneal edema resolved, choroidals
      started resolving, and intraocular pressure was controlled without medication.
      CONCLUSIONS: In patients presenting with acute angle closure secondary to
      Topiramate toxicity, choroidal drainage if indicated, is a safe and effective
      interventional procedure.

PMID- 18091457
TI  - Clinical comparison of pascal dynamic contour tonometry and goldmann applanation
      tonometry in asymmetric open-angle glaucoma.
AB  - PURPOSE: To investigate and compare the relationships between glaucomatous visual
      field loss and intraocular pressure (IOP) as measured by both Pascal dynamic
      contour tonometry (DCT) and Goldmann applanation tonometry (GAT). PATIENTS AND
      METHODS: All primary open-angle glaucoma and normal tension glaucoma patients
      seen between July 2005 and June 2006 with at least 2 sets of good-quality,
      bilateral DCT and GAT measurements were retrospectively identified. Additional
      inclusion criteria required that all subjects had repeatable, asymmetric
      glaucomatous visual field loss that corresponded with asymmetric glaucomatous
      optic neuropathy. After mean IOP values were computed and visual fields were
      scored using Advanced Glaucoma Intervention Study (AGIS) criteria, paired-eye
      comparisons were conducted using right versus left eyes and higher versus lower
      AGIS-score eyes. RESULTS: Sixty-seven (42 primary open-angle glaucoma, 25 normal
      tension glaucoma) subjects met all criteria for study inclusion. Per paired t
      test, mean DCT-IOP was significantly higher in the higher AGIS-score eyes
      compared with the lower AGIS-score eyes (16.3 vs. 15.5 mm Hg, P=0.004), whereas
      GAT-IOP was not significantly different in these same eyes (14.5 vs. 14.4 mm Hg,
      P=0.56). Mean IOP difference between the 2 methods was significantly larger in
      higher versus lower AGIS-score eyes (P<0.001), and 72% of the subjects
      demonstrated larger intermethod IOP differences in their higher AGIS-score eye
      compared with their lower AGIS-score eye (P<0.001; 95% confidence interval: 0.59
      0.82). Multivariate linear regression analysis revealed that AGIS-score
      differences between eyes were independently associated with both intermethod IOP
      differences between eyes (P=0.004) and central corneal thickness (CCT)
      differences between eyes (P=0.04). CCT, however, was not associated with
      intermethod IOP differences within or between eyes. CONCLUSIONS: These findings
      suggest that DCT-IOP is correlated with glaucomatous damage, and moreover, DCT
      IOP is more closely related to extent of glaucoma damage than is GAT-IOP. The
      most likely explanation for these results is that GAT-IOP systematically
      underestimates IOP compared with DCT-IOP. Our findings also support the
      hypothesis that corneal biomechanical factors other than CCT are major
      confounders of applanation tonometry measurements.

PMID- 18091458
TI  - The clinical utility of dynamic contour tonometry and ocular pulse amplitude.
AB  - PURPOSE: To determine if ocular pulse amplitude (OPA) as measured by dynamic
      contour tonometry (DCT) is related to severity of glaucoma, and if intraocular
      pressure (IOP) as measured by DCT is related to central corneal thickness (CCT).
      METHODS: Patients were selected from the Duke Eye Center glaucoma clinic. Fifty
      five eyes of 32 patients were included; right and left eyes were analyzed
      separately. CCT, OPA, DCT IOP, Goldmann applanation tonometry (GAT), Tonopen
      applanation tonometry (TAT), and systemic blood pressure were measured. Advanced
      Glaucoma Intervention Study score and mean deviation of visual field, and
      vertical and horizontal cup-disc ratios were recorded in a masked manner.
      Descriptive statistics were obtained, and OPA, DCT IOP, GAT, and TAT underwent
      univariate analyses to assess for relationships with predictor variables.
      RESULTS: OPA, DCT IOP, GAT, and TAT were positively associated with CCT and with
      having no surgical intervention for right and left eyes, and were negatively
      associated with vertical and horizontal cup-disc ratios. CONCLUSIONS: Increased
      OPA seems to correlate with less severe glaucoma and with increased CCT. DCT IOP
      seems to be affected by CCT along with GAT and TAT.

PMID- 18091459
TI  - Exposure of Ex-PRESS Miniature Glaucoma Devices: case series and technique for
      tube shunt removal.
AB  - PURPOSE: To report a series of cases involving Ex-PRESS Miniature Glaucoma Device
      exposure and discuss the surgical techniques we used to remove the shunts.
      METHODS: A retrospective chart review was performed to identify all patients who
      were referred for Ex-PRESS Miniature Glaucoma Device exposure between January
      2004 and December 2005. Demographic information, time to exposure, surgical
      technique for device implantation and removal, and patient outcomes after device
      removal were abstracted from the identified charts. In addition, we describe a
      surgical technique used to remove the exposed Ex-PRESS Miniature Glaucoma
      Devices. RESULTS: Six patients (8 eyes) experienced Ex-PRESS Miniature Glaucoma
      Device exposure. The average time to exposure was 8.5 months. In 2 eyes, the
      shunt had been inserted under a half-thickness scleral flap; in both these eyes
      and 1 additional eye, Mitomycin-C had been used during shunt insertion. At
      presentation with tube shunt exposure, all eyes had normal or elevated
      intraocular pressure. In 5 eyes, visual acuity worsened after the device was
      removed. All 8 patients required concomitant glaucoma surgery with device
      removal. CONCLUSIONS: As an increasing number of patients undergo filtration
      surgery with Ex-PRESS Miniature Glaucoma Devices, anterior segment surgeons
      should be aware of the potential for device exposure and methods for device
      removal.

PMID- 18091460
TI  - Making the most of the "honeymoon phase" of a deanship.
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- 18091461
TI  - A creative project to teach endocrinology pathophysiology.

PMID- 18091462
TI  - Predictors of success on National Council Licensure examination for registered
      nurses for accelerated baccalaureate nursing graduates.

PMID- 18091463
TI  - Documenting dimensions of caring using narratives.

PMID- 18091464
TI  - Teaching social justice using a pedagogy of engagement.
AB  - Teaching an undergraduate level diversity course with a health focus requires
      specific teaching methods. A pedagogy of engagement provides an effective
      strategy for exploring issues of race, class, gender, and structural inequalities
      that underlie health disparities. Engagement learning enhances understanding of
      theories of oppression and liberation presented in the course and highlights
      social justice issues.

PMID- 18091465
TI  - A responsive evaluation of an Aboriginal nursing education access program.
AB  - Nursing education access programs have been introduced in a number of countries
      to address the shortage of healthcare providers of Aboriginal descent. An
      evaluation study of a nursing education access program in Labrador, Canada, was
      undertaken using a Responsive Evaluation approach. Interviews and focus groups
      with program stakeholders were conducted. Program effectiveness was influenced by
      culturally relevant curriculum, experiential and authentic learning
      opportunities, academic and social support, and the need for partnership building
      between stakeholders. The authors report key findings resulting from the
      Responsive Evaluation.

PMID- 18091466
TI  - Customized library tutorial for online BSN students: library and nursing
      partnership.
AB  - Students returning to school to earn advanced degrees frequently experience
      difficulty accessing and retrieving information necessary to complete
      assignments. The authors describe the need, the development process, and the
      outcome of the partnership between nursing faculty and librarians to provide a
      customized library tutorial for online registered nurse to bachelor of science in
      nursing students.

PMID- 18091467
TI  - A technology-driven nursing faculty resource center.
AB  - With the overwhelming need to recruit and retain more nursing faculty, providing
      faculty development is imperative. The authors discuss the design,
      implementation, and evaluation of a virtual Nursing Faculty Resource Center,
      allowing easy replication in other nursing institutions.

PMID- 18091468
TI  - Stressors and coping strategies of students in accelerated baccalaureate nursing
      programs.
AB  - Baccalaureate students enrolled in 6 accelerated programs reported their stress
      level, sources of stress, and coping strategies. They differentiated helpful from
      unhelpful coping strategies. Findings indicate that accelerated nursing students
      experienced high stress levels over prolonged periods that exceeded stress levels
      in prior life events. Implications for nurse educators in accelerated nursing
      programs are explored.

PMID- 18091469
TI  - Are we moving toward an expanded role for part-time faculty?
AB  - The 30-year trend of increased use of part-time faculty in higher education
      warrants the following questions: Are part-time faculty roles changing in light
      of the increased presence of part-time faculty in the academia? In addition, what
      is their contribution to the educational institution's mission of research,
      teaching, and service? Boyer's model of scholarship was used in this research to
      answer these questions. The author discusses the research findings and their
      implications.

PMID- 18091470
TI  - Challenges and benefits of international clinical placements in public health
      nursing.
AB  - International clinical placements offer interested nursing students unique
      opportunities for development of nursing expertise and cultural competence
      skills. The authors review the professional literature regarding nursing student
      experiences in international sites, describe the development of international
      clinical sites in a required baccalaureate public health nursing course, and
      summarize challenges and benefits of the program.

PMID- 18091471
TI  - Copyright law and distance nursing education.
AB  - The authors present essential information regarding the copyright law and online
      education. This information provides the reader specific aids to assist in
      designing and implementing distance education courses within the bounds of the
      Technology, Education, and Copyright Harmonization Act and fair use guidelines.
      From their research, the authors, who are distance education experts, offer a
      wide array of educational and legal data to inform nurse educators.

PMID- 18091472
TI  - The impact of community college transfer on entry-level baccalaureate nursing
      student retention.
AB  - Student attrition is a major issue for entry-level baccalaureate science in
      nursing (BSN) programs. Where BSN students complete the prerequisite nursing
      courses may contribute to attrition. Because many BSN students satisfy
      prerequisite courses at community colleges (CCs), a better understanding
      regarding how a CC education impacts BSN student retention is needed. The author
      reviews the literature regarding factors that potentially impact entry-level BSN
      student retention after CC transfer.

PMID- 18091473
TI  - Is there a subgroup of patients with low back pain likely to benefit from
      mechanical traction? Results of a randomized clinical trial and subgrouping
      analysis.
AB  - STUDY DESIGN: Randomized Clinical Trial. OBJECTIVE: To identify a subgroup of
      patients with low back pain who are likely to respond favorably to an
      intervention including mechanical traction. SUMMARY OF BACKGROUND DATA: Previous
      research has failed to find evidence supporting traction for patients with low
      back pain. Previous studies have used heterogeneous samples, although clinical
      experts tend to recommend traction for a more limited subgroup of patients with
      low back pain. METHODS: Sixty-four subjects (mean age 41.1 year, 56.3% female)
      with low back and leg pain and signs of nerve root compression were randomized to
      receive a 6-week extension-oriented intervention with or without mechanical
      traction during the first 2 weeks. Between-group comparisons were conducted for
      changes in pain, disability, and fear-avoidance beliefs. Baseline variables were
      explored for potential as subgrouping criteria defining a subgroup of subjects
      likely to benefit from traction. RESULTS: The group receiving traction showed
      greater improvements in disability (adjusted mean difference in Oswestry change
      7.2 points) and fear-avoidance beliefs (adjusted mean difference in FABQPA change
      2.6 points) after 2 weeks. There were no between-group differences after 6 weeks.
      Two baseline variables were associated with greater improvements with traction
      treatment; peripheralization with extension movements and a crossed straight leg
      raise. CONCLUSION: A subgroup of patients likely to benefit from mechanical
      traction may exist. The results of this study suggest this subgroup is
      characterized by the presence of leg symptoms, signs of nerve root compression,
      and either peripheralization with extension movements or a crossed straight leg
      raise. Further research is needed to validate this finding.

PMID- 18091474
TI  - The effect of chronic low back pain on trunk muscle activations in target
      reaching movements with various loads.
AB  - STUDY DESIGN: A cross-sectional study of the timing of trunk muscle activations
      between 19 participants with chronic low back pain (LBP) compared with 19 matched
      controls. OBJECTIVE: To determine the effects of target height and load on trunk
      muscle coordination in whole body reaching tasks, and whether participants with
      chronic LBP display a shift in trunk muscle coordination performing these tasks.
      SUMMARY OF BACKGROUND DATA: Changes in the precise timing of trunk muscle
      activation may cause an initial episode of back pain, or contribute to the
      development of recurrent or chronic symptoms. However, most paradigms used to
      examine timing of trunk muscle activation did not necessitate large displacements
      of the trunk. METHODS: Participants with and without chronic LBP performed a
      series of bilateral reaching tasks to 3 target heights with 3 different loads
      held in the reaching hands. During reaching, joint motions were recorded with an
      optoelectric system and surface electromyographic signals were collected
      bilaterally from 5 trunk muscles: rectus abdominis, external oblique, internal
      oblique, iliocostalis lumborum, and the multifidis, and bilaterally from the
      deltoid muscle. The onset latencies of the antagonist trunk muscles relative to
      the deltoid muscle were analyzed to determine the effects of group, target height
      and load. RESULTS: Onset of trunk extensor muscles was significantly delayed in
      participants with chronic LBP compared with control subjects. Further, the onset
      latency of the antagonist trunk muscles increased with target distance, but
      decreased with target load. CONCLUSION: These findings suggest that a well
      documented control strategy generalizes beyond single joint movements and that
      individuals with chronic LBP display a shift in this strategy.

PMID- 18091475
TI  - From chronic low back pain to disability, a multifactorial mediated pathway: the
      InCHIANTI study.
AB  - STUDY DESIGN: Clinicoepidemiologic study in the Chianti area (Tuscany, Italy).
      OBJECTIVE: To evaluate whether performance measures of lower extremity function
      confounds the association of low back pain (LBP) with self-report disability in
      specific basic and instrumental activities of daily living (IADLs). SUMMARY OF
      BACKGROUND DATA: LBP is high prevalent in older population and has a negative
      impact on functional status. Studies on the pathway leading from LBP to
      disability are limited and often the role played by important confounders is not
      considered. METHODS: A total of 956 InCHIANTI study participants aged 65 and
      older able to complete performance-based tests of lower extremity function were
      included in this analysis. LBP was defined as a self-report of back pain "quite
      often-almost every day" in the past 12 months. Lower extremity function was
      evaluated administering the Short Physical Performance Battery. In addition,
      participants were asked to walk on a 7-m course and collect an object from the
      ground. Depressive symptoms (CES-D score), trunk flexion-extension range of
      motion, and hip-knee-foot pain were also considered in the pathway from LBP to
      disability. RESULTS: Compared with participants who did not report LBP, those
      with LBP were more likely to report difficulty in performing most activities of
      daily living. LBP was also associated with disability in the activities of
      bathing, doing the laundry, performing heavy household chores, cutting toenails,
      shopping, and carrying a shopping bag. The association between LBP and disability
      in selected ADLs and IADLs was no longer statistical significant, after
      adjustment for performance in lower extremity function, with exception of the
      activity of "carrying a shopping bag". CONCLUSION: The cross-sectional
      association between LBP and self-reported disability, in specific tasks is
      modulated by performance measures. Specific performance-based tests that explore
      the functional consequences of LBP may help design specific interventions of
      disability prevention and treatment in patients with LBP.

PMID- 18091476
TI  - Stage-specific sagittal spinopelvic alignment changes in osteoarthritis of the
      hip secondary to developmental hip dysplasia.
AB  - STUDY DESIGN: A retrospective, age- and sex-matched radiographic study.
      OBJECTIVE: To compare the sagittal spinopelvic alignment in patients with hip
      osteoarthritis (OA) stratified by stage with that of age-matched control groups.
      SUMMARY OF BACKGROUND DATA: OA of the hip resulting from developmental hip
      dysplasia could be a cause of low back syndrome. OA of the hip may induce changes
      in sagittal alignment compared with healthy subjects. METHODS: We studied 53
      patients with OA of the hip secondary to developmental hip dysplasia, including
      27 at the prearthritic/early stage (age, 34.0 years) and 26 at the
      advanced/terminal stage (age, 56.3 years). Comparisons were made with healthy
      females age-matched to each patient group (n = 13 and n = 15, respectively).
      Lateral roentgenograms of the lumbar spine and the hip joint were obtained in the
      upright position to determine pelvic inclination, sacral slope angle, lumbar
      lordotic angle (L1-L5), disc angle of L5/S1, and pelvic angle (by Jackson's
      method). RESULTS: Patients with pre/early-stage OA tended to have greater
      anterior pelvic inclination than healthy volunteers, although the difference was
      not significant. No significant differences were noted for other measurements.
      Lumbar lordotic and sacral slope angles were significantly greater in patients
      with advanced/terminal-stage OA than the control. Although lumbar lordotic and
      sacral slope angles decreased with aging in the healthy subjects, patients with
      OA retained the lumbar lordotic and sacral slope angles despite progression of OA
      with age. CONCLUSION: Pelvic inclination tended to increase in pre/early-stage OA
      patients. In healthy subjects, aging is associated with reduction of lumbar
      lordotic angle and tendency for posterior inclination of the sacrum. With aging,
      patients with OA maintained the lumbar lordotic angle and did not develop a
      posterior sacral slope angle.

PMID- 18091477
TI  - Diffusion-weighted magnetic resonance imaging of sacral insufficiency fractures:
      comparison with metastases of the sacrum.
AB  - STUDY DESIGN: Retrospective analysis of magnetic resonance imaging (MRI) for
      differentiating sacral insufficiency fractures from metastases of the sacrum.
      OBJECTIVE: To determine if a steady-state free precession (SSFP) diffusion
      weighted MRI is useful for differentiating sacral insufficiency fractures from
      metastases of the sacrum. SUMMARY OF BACKGROUND DATA: Conventional spin-echo
      sequence MRI is very sensitive for the detection of pathologic lesions in the
      sacrum, but the differential findings between sacral insufficiency fracture and
      metastasis are often not obvious because of the nonspecific changes of signal
      intensity. Another MR sequences for differentiation is needed. METHODS: Fourteen
      patients with sacral insufficiency fractures and 8 patients with metastasis at
      the sacrum were examined with MRI. Both the diffusion-weighted MRI and the spin
      echo MRI were performed in all patients. Diffusion-weighted MRI sequences were
      based on a SSFP sequence. RESULTS: All the insufficiency fractures and metastasis
      at the sacrum revealed low signal intensity on T1-weighted MRI; low or high
      signal intensity was revealed on T2-weighted MRI. The contrast enhanced T1
      weighted MRI showed strong enhancement at the sacrum in all cases of
      insufficiency fracture and metastasis. Diffusion-weighted MRI of the sacrum
      showed low signal intensity in all cases with sacral insufficiency fracture, but
      these images revealed high signal intensity in all cases with metastasis.
      CONCLUSION: SSFP diffusion-weighted MRI is capable of differentiating benign
      sacral insufficiency fractures from metastatic tumors of the sacrum.

PMID- 18091478
TI  - Translation and validation study of the Iranian versions of the Neck Disability
      Index and the Neck Pain and Disability Scale.
AB  - STUDY DESIGN: Cultural translation and psychometric testing. OBJECTIVE: To
      translate and validate the Iranian versions of the Neck Disability Index (NDI-IR)
      and the Neck Pain and Disability Scale (NPDS-IR). SUMMARY OF BACKGROUND DATA: The
      widely used the NDI and the NPDS scales have not been translated and validated
      for Persian-speaking patients with neck pain. This was to provide a validated
      instrument to measure functional status in patients with neck pain in Iran.
      METHODS: The translation and cultural adaptation of the original questionnaires
      were carried out in accordance with the published guidelines. One hundred and
      eighty-five patients with neck pain were participated in the study. Patients were
      asked to complete a questionnaire booklet including the NDI-IR, the NPDS-IR, the
      Iranian SF-36, and a visual analog scale (VAS) of pain. To carry out the test
      retest reliability, 30 randomly selected patients with neck pain were asked to
      complete the questionnaire booklet 48 hours later for the second time. RESULTS:
      Cronbach alpha coefficient for the NDI-IR was 0.88 and for the 4 subscales of the
      NPDS-IR was found to be satisfactory (ranging from 0.74 to 0.94). The NDI-IR and
      the NPDS-IR subscales showed excellent test-retest reliability (intraclass
      correlation coefficient ranged from 0.90 to 0.97; P < 0.01). The correlation
      between the NDI-IR and the NPDS-IR subscales and functional scales of the SF-36
      showed desirable results, indicating a good convergent validity (Pearson
      correlation coefficients ranged from -0.31 to -0.70). The correlation between the
      NDI-IR and the VAS was 0.71 and between the NPDS-IR subscales and the VAS ranged
      from 0.63 to 0.79 (P < 0.01). CONCLUSION: The Iranian versions of the NDI and
      NPDS are reliable and valid instruments to measure functional status in Persian
      speaking patients with neck pain in Iran. They are simple and easy to use and now
      can be applied in clinical settings and future outcome studies in Iran and other
      Persian speaking communities.

PMID- 18091479
TI  - Concurrent spinal cord untethering and scoliosis correction: case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe the technique, value, and risk
      of performing concomitant untethering of the spinal cord and scoliosis
      correction. SUMMARY OF BACKGROUND DATA: The incidence of intraspinal anomalies
      such as tethered cord, syringomyelia, Chiari malformation, and diastematomyelia
      is as high as 20% in infantile or juvenile and congenital scoliosis. Intraspinal
      anomalies that require intervention are commonly treated before surgical
      correction of the scoliosis to minimize the risk of neurologic complications. To
      our knowledge, this is the first documentation of the concurrent performance of
      these 2 procedures. METHODS: A 15-year-old boy presented with progressive
      kyphoscoliosis as well as lower extremity parasthesias and intermittent urinary
      incontinence. The thoracic and lumbar curves progressed to 65 and 80 degrees,
      respectively, with little flexibility. Preoperative magnetic resonance imaging of
      the entire spine revealed a low-lying conus at L4. The patient underwent
      untethering of the filum terminale in addition to posterior spinal fusion from T2
      to the pelvis. Intraoperative neuromonitoring included somatosensory-evoked
      potentials, motor-evoked potentials, continuous electromyography, triggered
      electromyography, and specific leads to monitor urethral and anal sphincter
      function. RESULTS: The patient tolerated the procedure well without complication.
      He was able to ambulate on postoperative day 2. The patient reported complete
      resolution of the lower extremity parasthesias and improvement in urinary
      symptoms. He continues to do well at 9 months after surgery. CONCLUSION:
      Concurrent untethering of the spinal cord and scoliosis correction with adequate
      intraoperative neuromonitoring is a viable option compared with a staged
      procedure in appropriately selected patients.

PMID- 18091480
TI  - Dorsally sequestered cervical disc herniation.
AB  - STUDY DESIGN: A case report of dorsally sequestered cervical disc herniation.
      OBJECTIVE: To present an unusual case of dorsally sequestered cervical disc
      herniation and to briefly review the literature on this condition. SUMMARY OF
      BACKGROUND DATA: There have been few reports of migration of cervical disc
      herniation to the posterior surface of the spinal canal. METHODS: A 72-year-old
      man experienced a sudden episode of weakness of both lower extremities after
      playing golf, which gradually progressed, resulting in inability to walk without
      aid. Magnetic resonance imaging revealed a well-defined, oval mass lesion on the
      left dorsal aspect of the spinal canal, which compressed the dural sac at the
      level of C7. The mass lesion was isointense on T1-weighted images and
      heterogeneously hyperintense on T2-weighted images, and contrast-enhanced
      magnetic resonance imaging demonstrated peripheral enhancement of the mass
      lesion. RESULTS: The patient underwent surgery consisting of decompressive
      laminoplasty of C6 to C7, partial laminectomy of T1, and removal of the mass
      lesion. Histologically, the mass lesion was diagnosed as a dorsally sequestered
      disc herniation. After surgery, the weakness of both lower extremities gradually
      resolved, and the patient was able to walk without assistance at 2 weeks after
      surgery. CONCLUSION: It is important to appropriately differentiate dorsally
      sequestered disc herniation from other epidural mass lesions such as extradural
      tumor before operation and essential to perform early and sufficient surgical
      decompression of the spinal cord to prevent poor postoperative course in cases of
      acute onset and rapid progression of the paralysis caused by disc herniation.

PMID- 18091481
TI  - Congenital thoracic scoliosis with unilateral unsegmented bar and concave fused
      ribs: rib osteotomy and posterior fusion at 1 year old, anterior and posterior
      fusion at 5 years old with a 36-year follow-up.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To document the 36-year follow-up of a
      patient with a fusion at age 1 year for congenital scoliosis with a unilateral
      unsegmented bar, convex hemivertebrae, and fused concave ribs. SUMMARY AND
      BACKGROUND DATA: Although early spine fusion has been recommended as a life
      saving measure for this problem, very little information exists as to the long
      term effect of such treatment. METHODS: Original chart, radiographs and
      photographs were compared to the situation 36 years after surgery. Pulmonary
      function tests and blood gasses were obtained at follow-up. RESULTS: At age 37,
      the patient is free of any respiratory complaints, is an avid golfer, is married
      with 2 children, and the manager of a large factory. His pulmonary volumes are
      about half of normal, but his blood gasses are normal. CONCLUSION: The early
      fusion prevented the customary severe progression of this condition and early
      death due to cor pulmonale. He is a fully functioning member of society. Will
      more modern treatments with lengthening of the hemithorax provide a better
      outcome? Only time will tell.

PMID- 18091483
TI  - Artificial disc versus fusion: a prospective, randomized study with 2-year follow
      up on 99 patients.
AB  - STUDY DESIGN: A total of 115 patients were randomized in a 1:1 ratio to a Bryan
      artificial disc replacement (56) or an anterior cervical fusion with allograft
      and a plate (59). OBJECTIVE: The purpose of this study is to examine the
      functional outcome and radiographic results of this prospective, randomized trial
      to determine the role of the Bryan artificial cervical disc replacement for
      patients with 1-level cervical disc disease. SUMMARY OF BACKGROUND DATA:
      Artificial cervical disc replacement has become an option for cervical
      radiculopathy. Previous studies have evaluated the efficacy of this alternative
      without the scientific rigor of a concurrent control population. This study is a
      pooled data set from 3 centers involved in the U.S. FDA Investigational Device
      Exemption trial evaluating the Bryan artificial cervical disc. METHODS: The
      purpose of this study is to examine the functional outcome and radiographic
      results of this prospective, randomized trial to determine the role of the Bryan
      artificial cervical disc replacement for patients with 1-level cervical disc
      disease; 12-month follow-up is available for 110 patients and 24 month follow-up
      complete for 99 patients. There are 30 males and 26 females in the Bryan group
      and 32 males and 27 females in the fusion group. The average age was 43 years
      (Bryan) and 46 years (fusion). Disability and pain were assessed using the Neck
      Disability Index (NDI) and the Visual Analog Scale (VAS) of the neck and of the
      arm pain. SF-36 outcome measures were obtained including the physical component
      as well as the mental component scores. Range of motion was determined by
      independent radiologic assessment of flexion-extension radiographs. We report a
      prospective, randomized study comparing the functional outcome of cervical disc
      replacement to an anterior cervical fusion with results of 99 patients at 2
      years. Prospective data were collected before surgery and at 6 weeks, 3, 6, 12,
      and 24 months after surgery. RESULTS: The average operative time for the control
      group was 1.1 hours and the Bryan Group 1.7 hours. Average blood loss was 49 mL
      (control) and 64 mL (Bryan). Average hospital stay was 0.6 days (control) and 0.9
      days (Bryan). The mean NDI before surgery was not statistically different between
      groups: 47 (Bryan) and 49 (control). Twelve-month follow-up NDI is 10 (Bryan) and
      18 (control) (P = 0.013). At 2-year follow-up, NDI for the Bryan group is 11 and
      the control group is 20 (P = 0.005). The mean arm pain VAS before surgery was 70
      (Bryan) and 71 (control). At 1-year follow-up, Bryan arm pain VAS was 12 and
      control 23 (P = 0.031). At 2-year follow-up, the average arm pain VAS for the
      Bryan group was 14 and control 28 (P = 0.014). The mean neck pain VAS before
      surgery was 72 (Bryan) and 73 (control). One-year follow-up scores were 17
      (Bryan) and 28 (control) (P = 0.05). At 2 years: 16 (Bryan) and 32 (control) (P =
      0.005). SF-36 scores: Physical component--Before surgery Bryan 34 and control 32.
      At 24 months: Bryan 51 and control 46 (P = 0.009). More motion was retained after
      surgery in the disc replacement group than the plated group at the index level (P
      < 0.006 at 3, 6, 12, and 24 months). The disc replacement group retained an
      average of 7.9 degrees of flexion-extension at 24 months. In contrast, the
      average range of motion in the fusion group was 0.6 degrees at 24 months. There
      were 6 additional operations in this series: 4 in the control group and 2 in the
      investigational group. There were no intraoperative complications, no vascular or
      neurologic complications, no spontaneous fusions, and no device failures or
      explantations in the Bryan cohort. CONCLUSION: The Bryan artificial disc
      replacement compares favorably to anterior cervical discectomy and fusion for the
      treatment of patients with 1-level cervical disc disease. At the 2-year follow
      up, there are statistically significant differences between the groups with
      improvements in the NDI, the neck pain and arm pain VAS scores, and the SF-36
      physical component score in the Bryan disc population.

PMID- 18091485
TI  - The effects of lifestyle intervention for hypertension on low back pain: a
      randomized controlled trial.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To assess the effects of a
      lifestyle intervention for hypertension on low back pain. SUMMARY OF BACKGROUND
      DATA: According to prospective etiologic studies, a causal association exists
      between certain lifestyle factors and low back pain. These factors are similar to
      those that elevate the risk for hypertension. Nevertheless, no randomized
      controlled trial has assessed effectiveness of lifestyle intervention for the
      treatment of hypertension on the prevalence of low back pain. METHODS: A total of
      731 hypertensive employees from 45 worksites were assigned to multidisciplinary
      lifestyle interventions for hypertension in a rehabilitation center or to routine
      care in occupational or primary healthcare services during 12 months.
      Questionnaire data on low back pain were used to assess the effects of the
      intervention on the extent of low back pain and disability. RESULTS: The changes
      in prevalence and duration of low back pain, and related disability did not
      differ between the 2 groups, although there were favorable changes in some risk
      factors, such as body weight and physical inactivity. Subgroup analyses among
      patients with moderately heavy or heavy work showed that the prevalence of low
      back pain during the previous 12 months decreased more in the intervention than
      in the control group. CONCLUSION: Multidisciplinary lifestyle intervention aimed
      to reduce hypertension is not effective at reducing prevalence of low back pain
      or disability. However, in the subgroup of persons doing moderate or heavy work,
      the intervention seemed to reduce prevalence of low back pain during the 1-year
      follow-up.

PMID- 18091486
TI  - One-year follow-up comparison of the effectiveness of McKenzie treatment and
      strengthening training for patients with chronic low back pain: outcome and
      prognostic factors.
AB  - STUDY DESIGN: A randomized controlled trial with multivariable analyses of
      prognostic factors. OBJECTIVE: To report the long-term outcome of McKenzie
      treatment compared with strengthening training. Further, to determine patient
      related factors associated with poor outcome 14 months after completion of
      treatment. SUMMARY OF BACKGROUND DATA: Exercise therapy is widely recommended for
      patients with chronic low back pain. However, reports vary considerably
      concerning characteristics of patients who will not respond to treatment.
      Knowledge of factors associated with poor outcome may assist identification of
      patients requiring special attention. METHODS: A total of 260 patients with
      chronic low back pain were included in a previously reported randomized
      controlled trial of McKenzie therapy versus strengthening training. Outcome
      variables were: functional status, pain level, work status, and use of healthcare
      services during follow-up. Also, factors associated with withdrawal during the
      intervention were sought identified. The following factors of possible prognostic
      significance were determined: levels of pain and disability, pain-distribution,
      duration of symptoms, smoking habits, leisure activities, workload, job
      satisfaction, treatment preference, outcome expectations, treatment modality
      received, compliance with home exercises during follow-up, and demographic
      variables such as age, gender, work status, and application for pension.
      Association between variables was examined by multiple logistic regression
      analysis and odds ratios. RESULTS: No differences in outcomes were found between
      the treatment groups at 14 months of follow-up. Low level of pain intensity and
      disability, sick leave at entry, low pretreatment expectations of future work
      ability, withdrawal during treatment, and discontinuance of exercises after the
      end of the treatment period were associated with poor outcome. CONCLUSION: Poor
      long-term outcome of exercise therapy for chronic low back pain can be explained
      by a number of patient-related factors. Different prognostic factors were
      associated with different outcomes. These factors were more important in
      determining outcome than the exercise-programs studied.

PMID- 18091487
TI  - The role of extracellular factors in human metastatic chordoma cell growth in
      vitro.
AB  - STUDY DESIGN: Human metastatic chordoma cells were isolated, and initial in vitro
      characterization was performed. Biochemical and physiologic changes were observed
      in response to pH, oxygen, and glucose. OBJECTIVE: The extracellular
      microenvironment directly affects metastatic chordoma cell phenotype in vitro.
      SUMMARY OF BACKGROUND DATA: Chordomas are primary bone tumors that usually occur
      in the spine or skull. Chordomas arise from embryonic notochordal remnants along
      the axial skeleton, most commonly the sacrum, followed by the base of the skull
      and the mobile spine. Due to a high degree of resistance to radiation and
      chemotherapy, chordomas eventually cause death by direct growth or by
      metastasizing to other organs. METHODS: Extracellular pH, oxygen, and glucose
      levels in the culture medium were controlled, and cell response was assessed
      using MTT staining, SDS-PAGE, Western blotting, tandem mass spectrometry, TUNEL,
      immunofluorescence, and flow cytometry. RESULTS: In this study, we present a new
      chordoma cell line established from metastatic tissue and novel data
      characterizing some aspects of chordoma cell phenotype in different conditions in
      vitro. Chordoma biologic markers were expressed in the new cell line. Alkaline pH
      dramatically increased intracellular protein tyrosine phosphorylation, metabolic
      activity, and albumin accumulation in the cells, while acidic pH caused
      apoptosis. CONCLUSION: The level of proliferation, apoptosis, and tyrosine
      phosphorylation, as well as the overall protein expression profile, strongly
      depended on extracellular media pH and oxygen/glucose levels. Chordoma's
      preferred extracellular microenvironment in vitro was rather alkaline, with an
      optimum at pH 8.5, and apoptotic changes were induced at acidic pH. We found that
      bovine serum albumin was accumulated by chordoma cells from the incubation media,
      and this accumulation depended on extracellular pH, with the highest accumulation
      at alkaline pH.

PMID- 18091488
TI  - Effect of uncovertebral joint excision on the motion response of the cervical
      spine after total disc replacement.
AB  - STUDY DESIGN: In vitro biomechanical study. OBJECTIVE: To quantify the effects of
      uncinatectomy on cervical motion after total disc replacement (TDR). SUMMARY OF
      BACKGROUND DATA: The effect of uncinatectomy on TDR motion is unknown. Partial
      uncinatectomy may be required to decompress the foramen; however, the residual
      uncinates can potentially limit TDR motion and serve as a source of progressive
      spondylosis. Complete resection of the uncinates may decrease this risk yet
      endanger destabilizing the segment. METHODS: Seven human cervical spines (C3-C7)
      (age, 63.4 +/- 6.9 years) were tested first intact and then after implantation of
      a metal-on-polyethylene ball-and-socket semiconstrained prosthesis at C5-C6.
      Following this, gradually increased uncinatectomy was performed in the following
      order: 1) right partial-posteromedial (two thirds), 2) right complete, and 3)
      bilateral complete resection. Specimens were tested in flexion-extension, lateral
      bending, and axial rotation (+/-1.5 Nm). Flexion-extension was tested under 150 N
      follower preload. RESULTS: TDR without uncinatectomy increased C5-C6 flexion
      extension range of motion from 8.4 degrees +/- 3.5 degrees to 11.6 degrees +/-
      3.4 degrees, but statistical significance was not reached (P > 0.05). Lateral
      bending decreased from 6.2 degrees +/- 2.2 degrees to 3.1 degrees +/- 1.4
      degrees, with a trend for statistical significance (P = 0.07). Axial rotation
      decreased from 5.5 degrees +/- 2.4 degrees to 4.3 degrees +/- 1.4 degrees after
      the implantation (P > 0.05). Both right partial and right complete uncinatectomy
      resulted in nearly symmetrical restoration of lateral bending to intact values
      and significantly increased flexion-extension compared with intact (P < or =
      0.05); however, axial rotation still did not differ from intact (P > 0.05).
      Complete bilateral resection also restored lateral bending to intact values (7.3
      degrees +/- 2.7 degrees, P > 0.05); however, it resulted in significant increase
      in range of motion in flexion-extension (14.1 degrees +/- 3.0 degrees, P < or =
      0.05) and axial rotation (8.7 degrees +/- 2.4 degrees, P < or = 0.05).
      CONCLUSION: Unilateral complete or even partial uncinatectomy can normalize
      lateral bending after TDR. Bilateral complete uncinatectomy is not necessary to
      restore lateral bending and may result in significantly increased range of motion
      in flexion-extension and axial rotation compared with intact values.

PMID- 18091489
TI  - Immature sheep spines are more flexible than mature spines: an in vitro
      biomechanical study.
AB  - STUDY DESIGN: Dynamic triaxial biomechanical testing of immature and mature ovine
      spine motion segments. OBJECTIVE: To compare torque-deflection parameters of
      mature and immature spine motion segments and to investigate whether scaling
      relationships apply between mature and immature motion segment torque-deflection
      responses. SUMMARY OF BACKGROUND DATA: While previous studies have examined the
      cervical region in a limited number of loading directions, a comprehensive
      multiaxial study of the response of the pediatric spine at all 3 spinal levels
      (cervical, thoracic, and lumbar) has not been performed. METHODS: Motion segments
      from cervical, thoracic, and lumbar levels were tested under moment application
      about 3 axes for newborn and 2-year-old sheep. Range of motion, neutral zone, and
      stiffness were calculated for each motion segment and compared for immature and
      mature spine. RESULTS: Immature spine motion segments exhibited a significantly
      larger range of motion (P < 0.001) and neutral zone (P < 0.001) and significantly
      lower stiffness (P < 0.001) in comparison to mature spine segments about the 3
      moment axes, at the 3 spinal levels tested. There were statistically significant
      interactions between specimen age and the moment axis and/or spinal level for
      some torque-deflection parameters. CONCLUSION: The significantly greater neutral
      zone of immature spine suggests greater ligament laxity. Significantly higher
      range of motion and lower stiffness of the immature spine may be implicated in
      spinal cord injury mechanisms and implies a change in relative tolerance of the
      spine to damage with spinal maturity. Significant statistical interactions
      between spinal maturity and moment axis or motion segment level suggest that
      scaling torque-deflection parameters from mature to immature spine may not be
      appropriate.

PMID- 18091490
TI  - High graft resorption rates with dense cancellous allograft in anterior cervical
      discectomy and fusion.
AB  - STUDY DESIGN: Radiographic review. OBJECTIVE: To determine whether dense
      cancellous allografts (DCAs) are associated with graft resorption when used in
      anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: The
      ideal graft material for ACDF remains to be identified. Purported advantages of
      DCA include compressive strength similar to that of cervical vertebrae, which may
      lessen the likelihood of graft pistoning. Additionally, the porous structure of
      DCA is argued to promote earlier/more complete ingrowth. For the same reasons,
      however, it could be postulated that DCA may be more prone to collapse and
      resorption. METHODS: DCAs were used in 27 patients undergoing plated ACDF at 40
      levels. Sagittal CT reconstructions were evaluated over the central portion of
      the graft for areas of resorption and bridging trabeculations. Fusion was
      assessed with flexion-extension radiographs. RESULTS: At mean 15 months (range,
      12-26 months), resorption of DCA was noted in 53% of levels. It was severe in
      10%, moderate in 23%, and mild in 20%. In only 53% of the levels did bridging
      trabeculations cover > or = 50% of the anterior-posterior depth of the disc
      space. The fusion rate was 82%, but no patient required revision surgery for
      symptomatic pseudarthrosis. CONCLUSION: DCA demonstrated high rates of resorption
      when used in ACDF. Although the majority of segments fused and no patient
      required revision for symptomatic pseudarthrosis, resorption led to voids within
      the graft such that only 53% of levels had bridging trabeculations covering more
      than half of the disc space. Despite theoretical benefits, due to a propensity to
      resorb, caution should be used when considering using DCA in ACDF.

PMID- 18091491
TI  - The source of axial pain after cervical laminoplasty-C7 is more crucial than deep
      extensor muscles.
AB  - STUDY DESIGN: Prospective study to investigate the incidence of axial pain in the
      3 different procedures of laminoplasty. OBJECTIVE: To inquire which is more
      important in the development of axial pain after laminoplasty: C7 or deep
      extensor muscles. SUMMARY OF BACKGROUND DATA: The etiology of axial pain remains
      largely unknown. Some surgeons have attempted to preserve the paravertebral
      muscles with innovative procedures of laminoplasty and thereby reduce the
      incidence of axial pain. Meanwhile, we have reported that axial pain can be
      prevented by avoiding inclusion of C7 in laminoplasty. METHODS: There were 91
      patients with myelopathy who underwent our original laminoplasty, in which the
      deep extensor muscles were completely preserved exclusively on the hinged side.
      Until 2001, all candidates for laminoplasty underwent this procedure from C3-C7
      (left-opened C3-C7 group, n = 37). From 2002, the same procedure was performed
      from C3-C6 (left-opened C3-C6 group, n = 31). From 2004, the opened side was
      changed from left to right (right-opened C3-C6 group, n = 23). Axial neck pain
      was graded as severe, moderate, or mild. Early pain during the first month after
      surgery and late pain during the first year after surgery were investigated. The
      laterality of early pain in the C3-C6 groups was recorded. RESULTS: Significant
      early pain graded severe or moderate was observed in 49% in the left-opened C3-C7
      group, but 15% in the left- or right-opened C3-C6 groups (P = 0.0008).
      Significant late pain was noted in 30% in the left-opened C3-C7 group and in 5.6%
      in the C3-C6 groups (P = 0.0036). Early axial pain, which usually was mild, was
      predominantly observed on the opened side in the C3-C6 groups. CONCLUSION: To
      prevent axial pain, C7 should not be included in cervical laminoplasty, while
      detachment of the deep extensor muscles does not result in significant axial
      pain.

PMID- 18091492
TI  - Spinal cord injury in patients with ankylosing spondylitis: a 10-year review.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate the clinical and
      functional outcomes in patients with spinal cord injury (SCI) and preexisting
      ankylosing spondylitis (AS). SUMMARY OF BACKGROUND DATA: AS alters the strength
      and biomechanical properties of the spine that renders it susceptible to fracture
      with minimal trauma. Neurologic involvement is common and outcomes largely depend
      on the early recognition and appropriate management. METHODS: A 10-year review
      (1996-2005) was carried out to identify all patients admitted with SCI associated
      with AS. The cause of injury, prehospital and emergency management, definitive
      treatment of fracture, final neurology, and functional outcomes were ascertained.
      Reasons for neurologic deterioration were determined. RESULTS: Eighteen patients
      were identified. In 15 patients, the injury resulted from trauma (fall 14, road
      accident 1) and in 3 the SCI followed spinal surgical interventions. Twelve of
      the 15 patients with traumatic injuries were able to walk immediately after the
      fall but subsequently deteriorated for various reasons. Spinal epidural hematomas
      developed in 3 patients (2 traumatic, 1 spinal intervention). The fractures were
      managed surgically in 3 patients, halo jacket was used in 2, and the remainder
      were managed expectantly on traction. Four patients died before discharge, 4 were
      able to walk with an aid at discharge, and the others were wheel chair dependent.
      CONCLUSION: Neurologic deficits were often subtle on initial presentation,
      resulting in many injuries being missed because of a low index of suspicion and
      poor visualization of lower cervical fractures on conventional radiographs.
      Extension of the ankylosed kyphotic cervical spine during conventional
      immobilization or for radiologic procedures resulted in neurologic deficits.
      Patients with an ankylosed cervical spine are normally unable to see the ceiling
      lying supine because of cervicothoracic kyphosis and use pillows to support their
      head. Cervical spine alignment in a similar flexed position is essential during
      immobilization or imaging. Medical alert cards as for patients with diabetes
      would be a way forward in correctly identifying patients with AS so that
      appropriate precautions can be instituted by emergency services.

PMID- 18091493
TI  - Bone morphogenetic protein-2 (BMP-2) in the treatment of pyogenic vertebral
      osteomyelitis.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To present results of
      recombinant human bone morphogenetic protein-2 (rhBMP-2) use in medically
      nonresponsive pyogenic vertebral osteomyelitis (PVO), treated by
      anterior/posterior debridement and instrumented fusion in the cervical, thoracic,
      and lumbosacral spine. SUMMARY OF BACKGROUND DATA: Surgical options for PVO vary,
      as do their outcomes, and can be complicated by recurrence, pseudarthrosis, and
      death. Although rhBMP-2 use in spinal fusion is increasing, its utility in PVO is
      unknown. Additionally, use in areas of infection is listed as a contraindication,
      although this is not supported by laboratory (animal) studies or clinical studies
      in long bones. METHODS: Between 2003 and 2005, 14 patients who underwent
      circumferential fusion for PVO were included in this study. Average patient age
      was 54 years (range, 27-77 years). Eight (57%) patients had 3 or more vertebral
      bodies involved. Diagnostic studies included radiographs, CT, MRI, and markers of
      infection [(C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white
      blood count (WBC)]. All patients underwent anterior fusion with rhBMP-2 inserted
      in structural allograft (11 patients) or titanium cylindrical cages (3 patients),
      followed by posterior instrumented fusion with autogenous iliac crest graft (8
      occurring on the same day). Follow-up averaged 22 months (range, 11-30 months).
      All were studied with plain radiographs, including flexion-extension lateral
      films and fine cut CT scans with reconstruction. Pain ratings were recorded by
      visual analog scores (VAS). RESULTS: Clinical resolution of infections,
      normalization of lab values, and bony fusion, based on dynamic radiographs and CT
      scans, were seen in all patients at latest follow-up. Staphylococcus aureus was
      the most frequently identified organism (8 patients). Four (29%) patients had
      positive blood cultures (all MRSA). Predisposing comorbidities were present in 12
      patients. Six patients had epidural abscesses. Eight (57%) patients presented
      with neurologic deficits, ranging from paraparesis to quadriplegia. Complete
      recovery was seen in 7 (quadriplegia unchanged). At 1 year, mean VAS pain scores
      improved significantly (P < 0.05) from 7.9 (range, 3-10) to 2.8 (range, 0-6).
      Perioperative complications (non-BMP related) occurred in 2 patients. There were
      no surgically-related deaths. CONCLUSION: rhBMP-2 use, in combination with
      antibiotics and circumferential instrumented fusion, provides a safe and
      successful surgical treatment of medically nonresponsive PVO, with solid fusions
      obtained, good clinical results, and no adverse side effects from the BMP.

PMID- 18091494
TI  - Clinical outcomes of 90 isolated unilateral facet fractures, subluxations, and
      dislocations treated surgically and nonoperatively.
AB  - STUDY DESIGN: A retrospective outcomes study. OBJECTIVE: The purposes of this
      study were 1) to identify plausible patient and interventional variables that
      influence the outcome of unilateral facet injuries and 2) to determine if
      patients return to normal general health status after unilateral facet injuries.
      SUMMARY OF BACKGROUND DATA: The management of unilateral subaxial cervical facet
      fractures and dislocations lacks agreement on treatment options and the variables
      that influence outcome. METHODS: Injury data, radiographs, and outcomes (North
      American Spine Society Cervical Follow-up Questionnaire and Short Form-36) were
      collected from 9 centers and 13 surgeons, members of the Spine Trauma Study
      Group. RESULTS: Causally motor vehicle accidents (49%) and sports (31%)
      predominated. The C6-C7 level accounted for 60% of injuries and C5-C6 represented
      17%. The mean SF-36 PCS score of the operative patients with follow-up >18 months
      was 6.70 points higher than the mean of the nonoperative patients (P = 0.017).
      The SF-36 Bodily Pain mean of all patients was 67.2 (SD = 27.6), significantly
      lower (more pain) than the normative mean of 75.2 (SD = 23.7) (P = 0.014).
      Nonoperative patients also reported a mean Bodily Pain score of 63.0 (SD = 30.5)
      that was significantly worse than normative values (P = 0.031). Similarly, the
      NASS PD mean score for all patients was 84.8 (SD = 17.9), significantly lower
      than the normative mean of 89.1 (SD = 15.5) (P = 0.014). CONCLUSION: To our
      knowledge this is the largest reported series of facet injuries to date and the
      only one using health-related quality of life instruments. Unilateral facet
      injuries of the subaxial cervical spine led to reported levels of pain and
      disability that are significantly worse than those of the healthy population.
      Although further study is required, we suggest that nonoperatively treated
      patients report worse outcomes than operatively treated patients, particularly at
      longer follow-up despite having a more benign fracture pattern. The presence of
      comorbidities, associated injuries, and advanced age adversely impact clinical
      outcomes.

PMID- 18091495
TI  - Shape modification of the Boston brace using a finite-element method with
      topology optimization.
AB  - STUDY DESIGN: Using a finite-element (FE) method to reshape the Boston brace, and
      evaluating the correction effect of the modified Boston brace in terms of Cobb
      angle. OBJECTIVE: This study aimed to reduce the weight of the Boston brace using
      a FE method with topology optimization. SUMMARY OF BACKGROUND DATA: The Boston
      brace is widely used to correct an abnormal spinal curve in adolescent idiopathic
      scoliosis. However, patients wearing the brace usually complain about discomfort
      caused by its bulkiness. METHODS: An FE model of a traditional Boston brace was
      constructed using the software ANSYS 9.0. The loading condition was taken from an
      X-sensor measuring contact pressures between torso and brace. Topology
      optimization was conducted to modify the Boston brace. Three patients wearing a
      traditional brace and then the modified brace were examined in terms of Cobb
      angle. RESULTS: For the patient with King Type III scoliosis, this modified brace
      was able to offer the same correction effect as the traditional brace, but the
      modified brace was lighter by about 12.4%, with the potential to be up to 18%
      lighter. CONCLUSION: Based on the traditional Boston brace, this FE model,
      combined with topology optimization, can effectively estimate redundant material
      distribution and accordingly custom-design a lighter brace without any loss of
      its corrective effect.

PMID- 18091496
TI  - Enhanced capacity for spontaneous correction of lumbar curve in the treatment of
      major thoracic-compensatory C modifier lumbar curve pattern in idiopathic
      scoliosis.
AB  - STUDY DESIGN: Retrospective radiographic review. OBJECTIVE: To evaluate the
      outcome of maximal selective thoracic correction with controllable corrective
      forces provided by cantilevel bending technique (CBT) for idiopathic scoliosis
      (IS) in the presence of widely deviated compensatory lumbar curve. SUMMARY OF
      BACKGROUND DATA: Current intraoperative instrumentation and fusion techniques for
      selective fusion involve undercorrection of the thoracic curve while allowing for
      spontaneous lumbar curve correction and maintaining overall coronal balance.
      Since the lumbar curve is nonstructural and compensatory, procedures for
      selective thoracic fusion should approximate the best possible correction of
      thoracic curve such that resultant spontaneous lumbar curve correction and
      compensation is maximized. METHODS: Thirty-seven consecutive IS patients with
      main thoracic compensatory minor "C" modifier lumbar curves underwent maximal
      selective thoracic correction by CBT at a single institution. Radiographs were
      analyzed before surgery, immediately after surgery, and at most recent follow-up
      (range, 2-6 years). RESULTS: A mean 83% thoracic correction was closely matched
      by a 81% lumbar correction at most recent follow-up. The mean thoracic curve
      correction/flexibility ratio was 2.4. Enhanced capacity for spontaneous
      correction of lumbar curve was evidenced by the mean correction/flexibility ratio
      of 1.2. Spontaneous correction of lumbar apical translation occurred in all
      patients. Global coronal imbalance was common before surgery (mean, 11 mm), and
      remained similarly so after surgery (mean, 12 mm). CONCLUSION: Use of CBT
      facilitates 3-dimensional control of corrective forces and allows for maximum
      selective instrumentation-assisted thoracic and spontaneous lumbar curve
      correction in patients with Lenke 1C or 2C IS.

PMID- 18091497
TI  - Volumetric changes of iliac crest autografts used to reconstruct the anterior
      column in thoracolumbar fractures: a follow-up using CT scans.
AB  - STUDY DESIGN: Patients with a thoracolumbar injury had a reconstruction of the
      anterior column using an tricortical iliac crest autograft. The volume and the
      length of the autograft were measured after 9 and 21 months using computed
      tomography. OBJECTIVE: To assess the volumetric change of an iliac crest
      autograft used to perform a reconstruction of the anterior column. SUMMARY OF
      BACKGROUND DATA: Iliac crest autografts are commonly used to reconstruct the
      anterior column following spinal fractures. However, very few reports have
      actually looked into the changes within the autograft following surgery. To our
      knowledge, no study has actually measured the loss of volume and length taking
      place within the graft using a CT scan. METHODS: From January 1995 through May
      2000, 27 patients of the 155 operated patients treated with a posterior-anterior
      stabilization of a fracture within the thoracic and lumbar spine were included in
      this study. Selection criteria were a postoperative CT and the reconstruction of
      the anterior column using an iliac crest autograft. A CT scan was performed
      before instrumentation removal and 1 year after instrumentation removal. These
      scans were used to evaluate the volume and length of the graft. RESULTS: There is
      a significant loss of graft volume (about 40%), half of which was not seen until
      after instrumentation removal. There is a correlation between the volumetric loss
      and the initial volume of the graft. The loss in length (24%) results in a
      correctional loss of the superior-inferior endplate angle totalling 12 degrees.
      All grafts showed good contact to the adjoining vertebrae with no case of a
      pseudarthrosis. CONCLUSION: The results show that more than a third of the
      initial graft volume is absorbed during the consolidation process. The loss was
      greater, the larger the volume of the initial graft was. The efficiency, however,
      was not dependent on the initial graft size.

PMID- 18091498
TI  - Accuracy of intraoperative plain radiographs to detect violations of intralaminar
      screws placed into the C2 vertebrae: a reliability study.
AB  - STUDY DESIGN: Cadaveric radiographic interpretation analysis. OBJECTIVE: To
      evaluate the reliability of plain radiographs for detecting potentially serious
      C2 ventral laminar violations during insertion of intralaminar screws. SUMMARY OF
      BACKGROUND DATA: With the potential serious complications (due to aberrant course
      of the vertebral artery) associated with insertion of C1-C2 transarticular
      screws, coupled with inherent difficulties with inserting either C2 pedicle or
      pars/isthmus screws, the intralaminar technique has recently gained popularity.
      METHODS: After visually confirming that we had placed bilateral screws entirely
      in the lamina in 12 cadaveric specimens, we obtained lateral radiographs. We
      repeated the screw insertions and radiographs for each of the following
      permutations: right in/left out, left in/right out, and both screws out. Three
      experienced spine surgeons blindly/independently assessed all 48 radiographs 3
      times. A screw projecting into the lateral mass was read as having perforated the
      ventral lamina. Accuracy was defined as percent agreement between actual and read
      position for 288 screws (48 L, 48 R times 3 raters). RESULTS: Accuracy was 77.4%.
      The highest accuracy was with both screws in (86.1%); the lowest with both out
      (63.9%). Left in-right out was 77.8%. Right in-left out was 81.9%. There was
      significantly higher incorrect identification of both out (rated "both in" in all
      but one; chi2 = 11.5, P < 0.05). Interrater reliability was moderate (k = 0.42)
      and sufficient for clinical use. Intrarater reliability was excellent for all
      three (k = 0.98, 1.00, 0.93). CONCLUSION: With both screws out, the accuracy was
      only 63.9%, suggesting that in over 36% of bilateral screw perforations, plain
      radiographs cannot detect the violation. While some of these might not cause
      clinical symptoms, others might cause subtle radiculopathy, myelopathy, or
      headaches. The presence of any of these should be worked up with a postoperative
      CT scan, as plain radiographs are not dependable.

PMID- 18091499
TI  - Risk factors for false positive transcranial motor evoked potential monitoring
      alerts during surgical treatment of cervical myelopathy.
AB  - STUDY DESIGN: Retrospective consecutive series review. OBJECTIVE: To examine
      performance of transcranial motor-evoked potential (TcMEP) monitoring in patients
      undergoing surgery for cervical myelopathy and potential risk factors for false
      positive alerts. SUMMARY OF BACKGROUND DATA: Although use of TcMEP monitoring has
      been increasing and has been specifically recommended in patients with cervical
      myelopathy, rates and risk factors for false positive alerts have not been
      established. METHODS: Intraoperative neuromonitoring data for 52 consecutive
      patients undergoing surgery for cervical myelopathy were reviewed. All major
      TcMEP alerts were identified. Comprehensive demographic and clinical data,
      preoperative imaging studies, operative, and anesthesia records were reviewed.
      RESULTS: Six of 52 patients (12%) experienced a major TcMEP alert consisting of
      sustained >80% loss of amplitude. There were no somatosensory-evoked potential
      (SSEP)-related alerts. In 2 cases, an intraoperative wake-up test was negative
      and in 3 cases, surgery was completed without a wake-up test and without recovery
      of TcMEP signals. No new postoperative neurologic deficits were observed in these
      patients. One patient with new postoperative weakness was correctly predicted by
      loss of TcMEP signals. No new deficit was observed in the remaining 46 patients.
      Statistical analysis revealed significantly higher body mass index (28.8 vs.
      35.0; P = 0.032) and length of surgery (191 vs. 283 minutes; P = 0.019) in
      patients with false positive alerts. CONCLUSION: In this series of cervical
      myelopathy patients, sensitivity and specificity of TcMEP for detection of
      clinically significant intraoperative cord injury were 100% and 90%,
      respectively. Sensitivity and specificity of SSEP were 0% and 100%, respectively.
      The positive predictive value of a TcMEP alert was 17%. Possible risk factors for
      false positive TcMEP alerts include obesity and increased length of surgery. This
      study supports superior sensitivity of TcMEP compared with SSEP monitoring but
      identifies a relatively high false positive rate even in a selected high-risk
      cervical myelopathy population when this modality is applied in practice.

PMID- 18091500
TI  - Minimal clinically important change of the Neck Disability Index and the
      Numerical Rating Scale for patients with neck pain.
AB  - STUDY DESIGN: Prospective, single-cohort study. OBJECTIVE: To assess the minimal
      clinically important change (MCIC) on the Neck Disability Index (NDI) and the
      Numerical Rating Scale (NRS) for pain in patients with neck pain. SUMMARY OF
      BACKGROUND DATA: Both measurement instruments are frequently used in research and
      clinical practice, but which changes are clinically relevant is still unknown.
      METHODS: The MCIC was estimated with 2 different methods, both integrating an
      anchor-based and distribution-based approach: the minimal detectable change (MDC)
      and the optimal cutoff point of the ROC curve. The study population consisted of
      183 patients with nonspecific neck pain. RESULTS: The results show an MDC of 10.5
      points for the NDI (scale range, 0-50) and 4.3 points for the NRS (scale range, 0
      10), and optimal cutoff points of the ROC curve of 3.5 for the NDI and 2.5 for
      the NRS. CONCLUSION: The estimated MCIC should be used as an indication for
      relevant changes in clinical practice. Using the optimal cutoff point of the ROC
      curve, false positives and false negatives are equally weighted; and if there are
      no objections doing so, the optimal cutoff point of the ROC curve may be a good
      choice.

PMID- 18091501
TI  - An outcome measure for Japanese people with chronic low back pain: an
      introduction and validation study of Japan Low Back Pain Evaluation
      Questionnaire.
AB  - STUDY DESIGN: Development of a nationwide patient-based outcome measure for
      patients with chronic low back pain (CLBP). OBJECTIVE: The purpose of this study
      was to develop and introduce a new means of measuring outcomes for Japanese
      individuals with CLBP (the Japan Low Back Pain Evaluation Questionnaire [JLEQ]),
      and to examine its validity and reliability by comparison with the Roland-Morris
      Disability Questionnaire (RDQ). SUMMARY OF BACKGROUND DATA: CLBP is a serious
      problem affecting the health and welfare of workers, especially laborers. The
      severity and disability it causes vary depending on cultural background and the
      psycho-emotional aspect of the patients. METHODS: The following items were tested
      for the JLEQ and the RDQ using psychometric analyses: content validity, construct
      validity, criterion validity, internal-consistency reliability, and test and
      retest reliability. RESULTS: A total of 195 patients with CLBP participated in
      this study. There were no floor and ceiling effects in the JLEQ. Cronbach's alpha
      coefficient was 0.971 and 0.893 for the JLEQ and RDQ, respectively. The test
      retest interclass correlation coefficient in the JLEQ was 0.886, indicating good
      test-retest reliability. Categorical principal component analysis showed that the
      construct structure consisted of 3 item clusters in the JLEQ. The factor loading
      patterns indicated that the JLEQ items were separated into 3 domains, i.e., a
      moderately loaded group, a less loaded group, and psychological conditions. The
      degree of correlation between the question items in the JLEQ and RDQ was
      evaluated using Akaike Information Criteria. CONCLUSION: The JLEQ was shown to be
      a valid and reliable questionnaire scale for measurement of patient-based
      outcomes in CLBP patients.

PMID- 18091502
TI  - The influence of the grade of chronicity on the outcome of multidisciplinary
      therapy for chronic low back pain.
AB  - STUDY DESIGN: Prospective longitudinal clinical study. OBJECTIVE: The objective
      of the study was to analyze the outcome of different stages of chronicity in
      patients with chronic low back pain treated with a multidisciplinary therapy.
      SUMMARY OF BACKGROUND DATA: Results of studies comparing different grades of
      chronicity in therapy for chronic low back pain have not been published so far.
      METHODS: A total of 387 patients with chronic low back pain for 3 months or
      longer and a corresponding sick leave for longer than 6 weeks underwent a 3-week
      standardized multidisciplinary therapy. At baseline (T0), patients were assigned
      into 3 groups of chronicity grades according to the classification of von Korff
      et al (Group A, Grades I and II; Group B, Grade III; Group C, Grade IV) and were
      prospectively followed. At the the 6-month follow-up (T1), 5 different therapy
      outcomes were analyzed and compared in the 3 groups: back-to-work status, generic
      health status (SF-36), pain intensity (visual analogue scale), functional
      capacity (Hannover back capacity score), and satisfaction with the therapy.
      RESULTS: At T0, patients in Group C had a higher pain level, a longer history of
      pain, and more general and more psychosomatic comorbidities than patients with
      lower levels of chronicity. All 3 treatment groups improved significantly in all
      outcome criteria between T0 and T1. In the total group, the back-to-work rate was
      67.4%. At the final follow-up, there were significantly better results in terms
      of functional capacity and pain level in patients with lower grades of chronicity
      but mostly due also to worse initial baseline values. Back-to-work rate,
      satisfaction with therapy, and the Mental Component Summary of the SF-36 did not
      show a significant difference at T1 between the groups analyzed. CONCLUSION:
      According to the results of this study, patients with chronic low back pain also
      derive significant benefit from a multidisciplinary treatment strategy in higher
      stages of chronicity. Therefore, therapy should not be limited to the patients in
      lower stages of chronicity.

PMID- 18091503
TI  - Surgical treatment of nonrheumatoid atlantoaxial degenerative arthritis producing
      pain and myelopathy.
AB  - STUDY DESIGN: A retrospective review. OBJECTIVE: The purpose of this study was to
      evaluate the clinical and pathologic findings and surgical treatment outcomes for
      atlantoaxial osteoarthritis. SUMMARY OF BACKGROUND DATA: Nonrheumatoid
      atlantoaxial osteoarthritic degeneration can occur at either the atlantodental
      articulation or lateral mass articulations. This condition may present with neck
      pain or myelopathy in the setting of a compressive degenerative pannus. There is
      a paucity of literature on this topic with only case reports and small case
      series. METHODS: A retrospective chart review was performed to identify patients
      treated for C1-C2 osteoarthritis. Patient demographics, clinical presentation,
      neurologic examination, visual analog pain scores, radiographic findings,
      surgical treatment, outcomes, and complications were recorded for each patient.
      RESULTS: Twenty-six patients (18 with pannus at the atlantodental articulation
      and 8 primarily with lateral mass articulation arthritis; 10 men, 16 women; mean
      age 74 years) were surgically treated for atlantoaxial osteoarthritis. Eleven
      patients presented primarily with complaints related to myelopathy (all with a
      degenerative pannus) and 15 presented with cervicalgia only. All patients were
      treated with posterior atlantoaxial arthrodesis, and 13 patients with myelopathy
      or severe canal compromise from an irreducible subluxation also had transoral
      odontoidectomy. All myelopathic patients had improvement in neurologic function
      (10 of 11 improved 1 Ranawat grade). Neck pain improved in 93% of patients with
      preoperative neck pain complaints (mean visual analog score before surgery = 7.0,
      follow-up = 1.3). Fusion was demonstrated in all patients with adequate follow
      up. CONCLUSION: Atlantoaxial osteoarthritis can result in neck pain and
      myelopathy. In the setting of a degenerative pannus and myelopathy, most patients
      will improve neurologically after transoral decompression and arthrodesis.
      Patients with pannus and no myelopathy were effectively treated with posterior
      fusion alone, although 2 with irreducible subluxation required an initial
      transoral decompression to allow realignment before fusion. Posterior arthrodesis
      alone provided significant pain relief in most patients.

PMID- 18091504
TI  - Pedicled omental flaps as an adjunct in the closure of complex spinal wounds.
AB  - STUDY DESIGN: A retrospective clinical study. OBJECTIVE: To evaluate the safety
      and efficacy of using an omental flap in complex spine reconstruction in patients
      at high-risk for wound dehiscence. SUMMARY OF BACKGROUND DATA: Postoperative
      wound dehiscence represents a major cause of morbidity in patients undergoing
      instrumented spinal reconstruction. A variety of approaches for the prevention
      and treatment of this problem have been previously described in the literature;
      however, the use of omental flaps has received little attention. METHODS: In this
      retrospective analysis, 5 patients were studied both clinically and
      radiographically. The study population included 4 women and 1 man, with a mean
      age of 49 years (range, 31-67 years). All patients underwent an omental flap
      procedure at the time of spinal reconstruction because of significant soft tissue
      defects or active spinal infection. Mean clinicoradiographic follow-up was 53
      months (range, 36-115 months). RESULTS: At the time of follow-up, all patients
      had well-healed surgical wounds with an acceptable structural and esthetic
      result. One patient in the study group experienced minor supra-fascial wound
      dehiscence. In terms of spinal outcome, all patients achieved successful bony
      arthrodesis; 1 patient, however, developed symptomatic adjacent segment
      degeneration and was treated by extension of the fusion construct. CONCLUSION: In
      patients undergoing thoracolumbar surgery who are at high risk of spinal wound
      dehiscence, closure using a pedicled omental flap is a viable procedure that may
      limit the risk of dehiscence and improve outcome.

PMID- 18091505
TI  - Surgical treatment of failed back surgery syndrome due to sagittal imbalance.
AB  - STUDY DESIGN: Retrospective study of consecutive patient series. OBJECTIVE: To
      review the etiology of failed back surgery syndrome due to sagittal imbalance and
      radiographic and clinical results of surgical treatment of these patients who
      were treated with combined anterior and posterior arthrodesis. SUMMARY OF
      BACKGROUND DATA: Sagittal imbalance after spinal fusion surgery may be a major
      source of pain and disability. Preventing iatrogenic sagittal imbalance should be
      a key objective during spinal fusion surgery. METHODS: Retrospective review of
      revision spine surgery due to sagittal imbalance treated with combined anterior
      and posterior spinal arthrodesis in the 19 patients. Outcome variables included
      radiographic measures of preoperative, postoperative, and follow-up films, and a
      clinical assessment using the Verbal Analogue Scale (VAS), Oswestry Disability
      Index, Macnab criteria, Satisfactory Index Instrument, and a review of
      postoperative complications. RESULTS: Mean age was 62 years (range, 49-74 years),
      and mean follow-up was 31 months (range, 24-37 months) for clinical and
      radiographic outcome variables. The mean preoperative sagittal imbalance was 116
      (+/-65) mm, which improved to 32 mm (+/-29) after surgery. Mean lumbar lordosis
      was 15 degrees (+/-20 degrees) before surgery, and increased to 38 degrees (+/-13
      degrees) at follow-up, an increase of 23 degrees. The mean VAS improved from 7.2
      (back pain), 6.8 (leg pain) before the surgery to 3 (back pain), 3.2 (leg pain)
      after the surgery (P < 0.0001). The mean Oswestry Disability Index scores
      improved from 62 (+/-11) before the surgery to 36 (+/-12) after the surgery (P <
      0.0001). Excellent or good outcome was demonstrated in 16 patients (84.2%).
      CONCLUSION: Most common causes of revision spine surgery due to sagittal
      imbalance were failure to enhance lumbar lordosis and adjacent disc degeneration
      after lumbar fusion surgery. These patients were effectively treated with a
      combined anterior and posterior arthrodesis. Following these surgical treatment,
      sagittal balance was generally improved with fair-to-good clinical outcomes, high
      patient satisfaction, and low perioperative complication rates.

PMID- 18091506
TI  - Re: Friedly J, Chan L, Deyo R. Increases in lumbosacral injections in the
      Medicare population: 1994 to 2001. Spine 2007;32:1754-60.

PMID- 18091507
TI  - Re: Papavero L, Heese O, Klotz-Regener V, et al. The impact of esophagus
      retraction on early dysphagia after anterior cervical surgery. Spine 2007;32:1089
      93.

PMID- 18091510
TI  - Re: Friedly J, Chan L, Deyo R. Increases in lumbosacral injections in the
      Medicare population: 1994 to 2001. Spine 2007;32:1754-60.

PMID- 18091511
TI  - Does brain natriuretic peptide interact with the immune system after cardiac
      transplantation?
AB  - Brain natriuretic peptide (BNP) is a marker of diagnosis and prognosis in
      patients with chronic heart failure. Stored in ventricular myocytes, it is
      released during ventricular stretch and increased transmural pressure. However,
      BNP behaves unusually after cardiac transplantation, with a failure to return to
      normal levels. This raises a question over whether other processes are involved
      in both its production and secretion. Several studies suggest BNP levels are
      associated with allograft rejection and coronary graft vasculopathy. Both of
      these processes have a single denominator in common, the activated immune system.
      This overview considers further evidence suggesting that BNP interacts with the
      immune system after cardiac transplantation.

PMID- 18091512
TI  - Good news for donor hearts: postconditioning.

PMID- 18091513
TI  - A mathematical risk-benefit analysis of composite tissue allotransplantation.
AB  - BACKGROUND: Composite tissue allotransplantation (CTA) represents a surgical
      technology whose risks and benefits are unclear. This is problematic for
      clinicians with respect to patient selection and counseling, and for policy
      makers in evaluating its merits. Our analysis represents a mathematical approach
      to risk and benefit estimation in CTA. METHODS: A Markov model was created to
      represent clinical and immunological outcomes after CTA. Esthetic outcomes were
      incorporated into the model by creating a disfigurement-related-disability
      severity score index based on existing literature. Composite tissue
      allotransplantation in a 30-year-old male was used as a base case analysis. We
      compared CTA against autogenous reconstruction as competing strategies.
      Sensitivity analyses were performed on the effect of preoperative esthetic
      morbidity and postoperative esthetic outcome. RESULTS: Our base-case showed CTA
      to be the preferred strategy-conferring a benefit of 4.47 esthetic-outcome
      adjusted life years. Sensitivity analyses showed CTA to be the preferred strategy
      if the preoperative disability severity score was greater than 5, and if the
      severity score after autogenous reconstruction was greater than 7. CONCLUSION:
      Our model estimates a theoretical risk-benefit threshold for CTA. The model
      itself can be refined as clinical experience with CTA grows and can incorporate
      economic and quality-of-life parameters.

PMID- 18091514
TI  - C4d-positive chronic rejection: a frequent entity with a poor outcome.
AB  - BACKGROUND: Chronic rejection (CR) is an important cause of kidney graft loss.
      Some studies have suggested the role of antibodies mediating chronic graft
      dysfunction. In this context, C4d identification is an important tool to evaluate
      antibody-mediated rejection. METHOD: This is a retrospective study that analyzed
      80 patients with histological diagnosis of chronic allograft nephropathy (CAN)
      according Banff 97 and no evidence of transplant glomerulopathy. These patients
      had renal biopsies available for C4d immunoperoxidase staining at the time of
      diagnosis. Cases were reclassified by the presence of C4d in peritubular
      capillaries. RESULTS: C4d was negative in 30 cases (37.5%) and positive in 50
      (62.5%). C4d+ group had more female and highly sensitized patients (PRA) at
      transplant. All variables were similar between C4d- and C4d+ cases at diagnosis
      time, but more C4d+ patients presented proteinuria (>0.3 g/L). Patients were
      submitted to various immunosuppression regimens after the CAN diagnosis. Four
      years after the diagnosis, death-censored graft survival was 87% for C4d- and 50%
      for C4d+ (P=0.002). In the multivariate Cox regression analysis, C4d+, PRA>10%,
      and vascular intimal proliferation were the variables that present higher
      relative risk for graft loss. CONCLUSION: These data indicate that C4d positive
      chronic rejection is very common, associated with proteinuria, and has a poor
      outcome. A larger study is warranted to identify which immunosuppressive regimen
      may modify the poor course of this entity.

PMID- 18091515
TI  - Donor biopsy and kidney transplant outcomes: an analysis using the Organ
      Procurement and Transplantation Network/United Network for Organ Sharing
      (OPTN/UNOS) database.
AB  - BACKGROUND: Although the degree of glomerulosclerosis on pretransplant donor
      biopsy is one criterion used in the decision to accept a deceased donor kidney,
      its relationship with graft survival remains controversial. This study compared
      graft survival with the degree of glomerulosclerosis found on donor biopsy. We
      also examined the agreement in degree of glomerulosclerosis between paired
      kidneys. METHODS: Biopsy results from 12,129 adult deceased donor transplants
      between January 1, 2000 and December 31, 2005 were identified in the Organ
      Procurement and Transplantation Network/United Network for Organ Sharing data, as
      of September 11, 2006. Of these, 2696 donors had both kidneys biopsied and
      subsequently transplanted. RESULTS: Among the groups with greater than 5%
      glomerulosclerosis, there was no statistically significant difference in graft
      survival rates (log-rank, P=0.44). The overall graft survival rates of the 0-5%
      group were significantly superior to those of the >5% groups (1-, 3-, and 5-year
      rates: 85.9%, 72.4%, and 59.0% for 0-5% group vs. 81.6%, 68.1%, and 53.6% for >5%
      group, log-rank P<0.001). Agreement between paired kidneys from the same donor
      was highest for the 0-5% glomerulosclerosis groups (90.6% for pairs with 0-5%
      glomerulosclerosis in the left kidney vs. 42.5% for pairs with >5%
      glomerulosclerosis in the left kidney). CONCLUSION: Donor kidneys with less than
      6% glomerulosclerosis were associated with better graft outcomes and intrapair
      agreement in the degree of glomerulosclerosis. Among kidneys with greater than 5%
      glomerulosclerosis, the degree of glomerulosclerosis did not help predict graft
      outcomes. Sampling error may contribute to the lack of outcome differences seen
      among these kidneys, given the low intrapair agreement.

PMID- 18091516
TI  - Is the corrected-creatinine model for end-stage liver disease a feasible strategy
      to adjust gender difference in organ allocation for liver transplantation?
AB  - BACKGROUND: The Model for End-stage Liver Disease (MELD) scoring system is used
      for organ allocation in liver transplantation. Female cirrhotic patients have
      lower glomerular filtration rates (GFR) than males for the same creatinine (Cr)
      level. Correcting the Cr in females for the same GFR as in males shows that
      females have lower MELD scores and therefore a lower priority for liver
      transplantation; however, there has been no outcome data that justifies this
      modification. METHODS: We investigated 472 cirrhotic patients, comparing the
      mortality rate between males and females in relation to MELD and corrected-Cr
      MELD. RESULTS: Compared to females, male patients had a higher MELD (14.5+/-5.5
      vs. 13.8+/-5.7) and significantly higher GFR (61.7+/-21.4 vs. 54.7+/-25.6
      mlLmin/1.73 m, P=0.0002) because their Cr value was higher (1.4+/-0.4 vs. 1.3+/
      0.5 mg/dL, P=0.0002). The corrected-Cr MELD score in females was higher (15.7+/
      6.3) compared to the MELD in their original counterpart (P<0.0001) and the males
      (P=0.060). Female and male patients had a similar 3-month mortality rate (6.7%
      vs. 6.3%) and MELD (21.9+/-8.6 vs. 21.7+/-8.9) among deceased patients. At 6
      months, female patients tended to have a lower mortality (12.5% vs. 14.7%) and a
      lower MELD (18.9+/-7.7 vs. 19.4+/-8.5) in deceased patients. However, at 9 and 12
      months, females had a consistently higher mortality (25% vs. 21.2% and 37.5% vs.
      31.3%, respectively) but lower MELD scores than males by 0.3-1 point.
      CONCLUSIONS: Using corrected-Cr MELD, which would prioritize female patients for
      liver transplantation, may only be justified in predicting intermediate-term (9-
      and 12-month), but not short-term (3- and 6-month) mortality.

PMID- 18091517
TI  - Allosensitization of islet allograft recipients.
AB  - BACKGROUND: The immune monitoring of islet transplant recipients includes the
      assessment of panel reactive antibodies (PRA). A negative association of PRA+
      with allogeneic solid organ graft survival has been recognized, but scattered
      data is available for islet transplantation. METHODS: We performed a
      retrospective analysis of PRA status in 66 patients with type 1 diabetes mellitus
      recipient of islet allografts between 1985 and 2006. RESULTS: Pretransplant PRA+
      was observed in 10 subjects in the old trials and associated with kidney
      transplantation and/or pregnancies. Thirteen subjects displayed PRA+ at follow
      up, eight of whom were de novo. Overall, PRA+ did not correlate with islet graft
      outcome: long-term graft survival was observed in the presence of basal or
      persistent PRA+ and graft dysfunction occurred also in the absence of PRA+. Loss
      of graft function was associated with PRA+ after lowering of immunosuppression or
      after infection episodes. Loss of C-peptide did not affect kidney graft function
      even in simultaneous islet-kidney transplant recipients. Mostly, PRA remained
      negative under adequate immunosuppression. Patients whose immunosuppression was
      discontinued invariably developed PRA+. CONCLUSIONS: Monitoring of PRA under
      immunosuppression may have little clinical value under adequate immunosuppression
      in islet transplant recipients. The implications of allosensitization after
      discontinuation of immunosuppression need to be evaluated to define the real
      clinical impact in this patient population.

PMID- 18091518
TI  - Evaluation of reliability and validity of Spanish version of the end-stage renal
      disease symptom checklist-transplantation module.
AB  - BACKGROUND: Although health-related quality of life (HRQoL) of patients with a
      renal transplantation is an important variable, it has received little attention
      and only a few Spanish validated measurement instruments are available. The aim
      of this study was to assess the psychometric properties of the Spanish version of
      the End Stage Renal Disease Symptom Checklist-Transplantation Module (ESRD-SCL),
      a specific questionnaire for measuring HRQoL of kidney transplant patients.
      METHODS: This prospective study to validate the ESRD-SCL included 307 patients
      who received a first kidney transplant. Patients filled out the ESRD-SCL, the
      EuroQol-5D and the Short Form-36 Health Survey at pretransplant, after 3 months,
      6 months, and 1 year of follow-up. A complete set of sociodemographic and
      clinical data was also collected. RESULTS: Mean age of patients was 51.6 years
      (SD+/-12) and 59.2% were men. A total of 24% had suffered initial allograft
      dysfunction and 18% had acute rejection. A six-dimensional factorial structure
      could be discerned. These dimensions were different from the original
      questionnaire and explained 56.07% of the variance. Internal consistency was good
      (Cronbach alpha = 0.91 for the overall score and 0.60-0.86 for dimensions). A
      statistically significant moderate correlation was observed between the Short
      Form-36 and EuroQol-5D with the ESRD-SCL dimensions and with some of the clinical
      and sociodemographic variables. CONCLUSIONS: The Spanish version of the ESRD-SCL
      is a useful, user-friendly instrument for measuring the HRQoL related to the side
      effects on immunosuppression treatment of renal transplant patients more
      accurately.

PMID- 18091519
TI  - A lower incidence of cytomegalovirus infection in de novo heart transplant
      recipients randomized to everolimus.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection in recipients of cardiac transplants
      is associated with higher rates of morbidity. A recent phase III trial showed
      highly significantly (P<0.001) lower CMV rates with the proliferation signal
      inhibitor everolimus compared to azathioprine (AZA). To better define this
      association, data on CMV risk factors were collected retrospectively and
      analyzed. METHODS: Data on CMV risk factors from a multicenter phase III trial on
      de novo heart transplant recipients (n=634) receiving a triple immunosuppressive
      regimen randomized to everolimus 1.5 mg/day (group 1), everolimus 3 mg/day (group
      2), or AZA (group 3) were merged with prospectively collected CMV-related outcome
      data and analyzed. RESULTS: CMV-positive donors (D+) and CMV-negative recipients
      (R-) were evenly distributed across groups 1-3 at 36/209 (17.2%), 48/211 (22.7%),
      and 38/214 (17.8%), respectively. CMV prophylaxis had been given for a mean (SD)
      of 175 (127.8), 183 (137.1), and 177 (132.9) days, respectively. In the high-risk
      D+/R- subgroup with prophylaxis, the proportions of patients with CMV infection
      compared with group 3 (12/29 [41.4%]) were 3/25 (12.0%) in group 1 (P=0.031) and
      6/36 (16.7%) in group 2 (P=0.049). In D+/R+ subgroups either with or without
      prophylaxis, the everolimus groups had less CMV disease (P<0.001). The incidence
      of CMV syndrome, organ involvement, and laboratory evidence was lower with
      everolimus use compared to AZA. CONCLUSIONS: Everolimus is associated with lower
      rates of CMV infection, syndrome, or organ involvement, suggesting an additional
      advantage from the use of everolimus in cardiac transplant recipients.

PMID- 18091520
TI  - Improvement in 3-month patient-reported gastrointestinal symptoms after
      conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in
      renal transplant patients.
AB  - BACKGROUND: The benefit of conversion from mycophenolate mofetil (MMF) to enteric
      coated mycophenolate sodium (EC-MPS) in terms of gastrointestinal symptom burden
      has been evaluated previously using patient-reported outcomes. However, data are
      lacking concerning the sustained effect of conversion over time, and the
      potential impact of concomitant calcineurin inhibitor. METHODS: In this 3-month,
      prospective, multicenter, longitudinal, open-label trial, MMF-treated renal
      transplant patients with gastrointestinal symptoms receiving cyclosporine or
      tacrolimus were converted to equimolar doses of EC-MPS. Change in
      gastrointestinal symptom burden was evaluated using a validated Gastrointestinal
      Symptom Rating Scale (GSRS). RESULTS: A significant improvement in GSRS score was
      observed from baseline (2.61, 95% CI 2.54-2.68) to month 1 (1.87, 95% CI 1.81
      1.93) after conversion to EC-MPS and was sustained to month 3 (1.81, 95% CI 1.74
      188; both P<0.0001 versus baseline). The mean change in overall GSRS score from
      baseline to month 1 was -0.74 overall (cyclosporine: -0.73 and tacrolimus: -0.74;
      all P<0.0001 versus baseline), with a slight further improvement (-0.79) at month
      3 (cyclosporine: -0.82 and tacrolimus: -0.78; all P<0.0001 versus baseline). A
      significant improvement in GSRS subscale scores was also observed in the total
      population regardless of calcineurin inhibitor at month 1, sustained to month 3
      (all P<0.0001 versus baseline). The improvement in GSRS score postconversion was
      similar in African-American and non-African-American patients, and in diabetic
      and nondiabetic patients. CONCLUSIONS: This exploratory study in 728 patients
      demonstrates that following conversion from MMF to EC-MPS, regardless of
      concomitant calcineurin inhibitor, GSRS is improved and sustained over 3 months.

PMID- 18091521
TI  - Acute lung transplant rejection is associated with localized increase in T-cell
      IFNgamma and TNFalpha proinflammatory cytokines in the airways.
AB  - BACKGROUND: Allograft rejection remains a major cause of morbidity and mortality
      after lung transplantation and is associated with increased gene expression for
      proinflammatory cytokines. T cells are a major cell type involved in graft
      rejection. There have been no previous studies of cytokine production by T cells
      from blood, bronchoalveolar lavage (BAL), and intraepithelial T cells from
      bronchial brushings (BB) during rejection episodes; we hypothesized that T-cell
      proinflammatory cytokines would be increased in the airways during rejection
      episodes despite standard immunosuppression regimens. METHOD: To investigate
      changes in cytokine profiles during rejection episodes, whole blood, BAL, and BB
      from stable lung transplant patients and those with acute rejection were
      stimulated in vitro and intracellular cytokine production by CD8- (CD4+) and CD8+
      T-cell subsets determined using multiparameter flow cytometry. RESULTS:
      Transforming growth factor (TGF)-beta was significantly decreased in blood CD4+
      and CD8+ T cells while interferon (IFN)-gamma and tumor necrosis factor (TNF)
      alpha were significantly increased in BAL CD4+ and CD8+ T cells in patients with
      evidence of rejection. There was no change in CD4:CD8, interleukin (IL)-2, or IL
      4 between stable and rejecting groups. CONCLUSIONS: Acute lung transplant
      rejection is associated with decreased intracellular T-cell TGFbeta in blood and
      increased intracellular IFNgamma and TNFalpha in BAL CD4+ and CD8+ T cells. Drugs
      that effectively reduce airway T-cell IFNgamma and TNFalpha proinflammatory
      cytokine production may improve current protocols for reducing acute graft
      rejection in lung transplant patients.

PMID- 18091522
TI  - Prevention of osteoporosis and hypogonadism by allogeneic ovarian transplantation
      in conjunction with intra-bone marrow-bone marrow transplantation.
AB  - BACKGROUND: We investigated the effects of ovarian allograft in conjunction with
      intra-bone marrow-bone marrow transplantation (IBM-BMT) on estrogen deficiency in
      mice. METHODS: Female C57BL/6 mice underwent ovariectomy (OvX). After 3 months,
      the mice were irradiated at 9.5 Gy, and the bone marrow cells (BMCs) of female
      BALB/c mice (8 weeks old) were then injected into the bone cavity of the B6 mice.
      Simultaneously, allogeneic ovaries from BALB/c mice were transplanted under the
      renal capsules of the B6 mice. RESULTS: Three months after the transplantation,
      the hematolymphoid cells were found to be completely reconstituted with donor
      derived cells. The transplanted ovary tissues under the renal capsules were
      accepted without using immunosuppressants; there were a large number of growing
      follicles at different stages of development. Atrophic endometrium and its glands
      were also recovered by ovarian transplantation (OT). The transplanted allogeneic
      ovaries secreted estrogen at normal levels. Furthermore, bone loss was prevented
      to a certain extent. CONCLUSIONS: These findings suggest that IBM-BMT+OT will
      become a valuable strategy for young women with malignant tumors to prevent
      premature senescence, including hypogonadism and osteoporosis, after
      radiochemotherapy.

PMID- 18091523
TI  - Operational tolerance to class I disparate lungs can be induced despite
      pretransplant immunization with class I allopeptides.
AB  - BACKGROUND: Using a class I-disparate swine lung transplant model, we examined
      whether an intensive course of tacrolimus could induce operational tolerance and
      whether preoperative allopeptide immunization would prevent the development of
      tolerance. METHODS: Left lung grafts were performed using class I-disparate
      (class II-matched) donors. Recipients were treated with 12 days of postoperative
      tacrolimus. Three recipients were immunized prior to transplantation with class I
      allopeptides. Three other recipients were not immunized. RESULTS: The
      nonimmunized recipients maintained their grafts long term (>497, >451, and >432
      days), without developing chronic rejection. The immunized swine also maintained
      their grafts long term (>417, >402, >401 days), despite developing a variety of
      in vitro and in vivo responses to the immunizing peptides, as well as having
      strong mixed lymphocyte reactions to donor cells prior to transplantation.
      CONCLUSIONS: Using only a brief course of tacrolimus, we have been able to induce
      a state of operational tolerance in a class I-disparate preclinical lung
      transplant model. Moreover, preoperative alloimmunization did not block tolerance
      induction or induce chronic rejection. These data show that it is possible to
      create a state of operational tolerance to lung allografts even in the presence
      of donor-sensitized cells.

PMID- 18091524
TI  - After four hours of cold ischemia and cardioplegic protocol, the heart can still
      be rescued with postconditioning.
AB  - BACKGROUND: There is evidence that ischemia lasting more than 4 hours affects
      cardiac allograft survival. Ischemia and reperfusion are associated with
      additional deleterious effects. Protective effects of preconditioning are already
      being used but protocols based on postconditioning have not been evaluated. We
      tested the impact of postconditioning on hearts maintained in the cold for a long
      period of total global ischemia and we compared the results with those obtained
      with pyruvate, a cardioprotective molecule. METHODS: Isolated working rat hearts
      were subjected to a global total ischemia (4 h/4 degrees C), followed by 45 min
      of reperfusion. Postconditioning consisted of brief total global ischemia applied
      three times during the onset of reperfusion (ischemia: 30 sec, reperfusion: 30
      sec). Superoxide anion production and collagen content were evaluated on
      cryosections. RESULTS: Our results showed that postconditioning led to
      improvements in cardiac functions that were comparable to those conferred by
      pyruvate. Postconditioning reduced myocardial damage, gave better functional
      recovery, and better preserved the collagen content. It reduced the duration of
      arrhythmias at the onset of reperfusion. In the postconditioning group, this
      improvement was associated with a reduction in superoxide production.
      CONCLUSIONS: In conclusion, our study showed that postconditioning induced good
      cardioprotective effects in a long cold (4 hr/4 degrees C) ischemia protocol and
      led to lower O2 production in part mediated by the reduction in NAPDH oxidase
      activity. It is interesting to note that, in our experimental conditions, the
      beneficial effects of postconditioning were comparable to those produced by
      pyruvate.

PMID- 18091525
TI  - Apoptosis and regeneration of sinusoidal endothelial cells after extended cold
      preservation and transplantation of rat liver.
AB  - BACKGROUND: Sinusoidal endothelial cells (SECs) are particularly susceptible to
      cold ischemia-reperfusion (I/R) injury. We have examined the process of injury
      and recovery of graft after cold-preserved liver transplantation, with special
      focus on the proliferation of SECs and regulatory mechanisms involved. METHODS:
      Male SD rats were divided into two groups according to length of cold
      preservation time in University of Wisconsin [UW] solution of graft: UW1h group
      and UW12h group. Graft function, incidence of apoptosis, proliferation of SECs
      and the expression of related regulatory factors were assessed after orthotopic
      liver transplantation (OLT). RESULTS: SECs are more sensitive to apoptosis
      induced by cold I/R injury compared with hepatocytes. Using bromodeoxyuridine and
      rat endothelial cell antigen-1 double immunostaining assay, SECs exhibited a
      delayed proliferation in comparison with hepatocytes, reaching a peak at 72 hr in
      UW1h group and 96 hr in UW12h group, respectively. Vascular endothelial growth
      factor increased at 24 hr after reperfusion, and peaked at 72 hr in both groups.
      Flt-1 and flk-1 expression was found to be mainly limited to SECs, with a peak in
      expression occurring between 72 and 96 hr, which coincided with the peak in SEC
      proliferation in UW1h group. However, flt-1 was found to be reduced significantly
      at any time throughout the experiments in UW12h group compared to sham.
      CONCLUSION: The delayed recovery of rat liver after extended cold preservation
      and transplantation correlates with a retarded regeneration of SECs due to
      increased apoptosis and reduced expression of flt-1. These results suggest that
      SECs play an important role in cold-preserved liver transplantation.

PMID- 18091526
TI  - The mTOR inhibitor everolimus induces proteinuria and renal deterioration in the
      remnant kidney model in the rat.
AB  - BACKGROUND: Under certain circumstances the nonnephrotoxic, antiproliferative,
      immunosuppressive mammalian target of rapamycin (mTOR) inhibitors can cause renal
      deterioration and proteinuria after conversion from calcineurin inhibitors,
      especially in long-term renal transplant patients with low glomerular filtration
      rates. The mTOR inhibitors also show an impaired glomerular healing reaction
      during acute renal injury in experimental mesangial proliferative
      glomerulonephritis. In this study, everolimus treatment was investigated in a low
      nephron number model, the remnant kidney model in rats. METHODS: The remnant
      kidney model was induced by uninephrectomy and infarction of 2/3 of the remaining
      kidney in 31 male Sprague-Dawley rats. Three days after disease induction, rats
      were randomly treated either with everolimus or vehicle. Changes in progression
      of renal disease were investigated by immunohistochemistry on days 22 and 38
      after disease induction. RESULTS: In the remnant kidney model, everolimus
      treatment worsened chronic disease progression as assessed by increased
      proteinuria, glomerulosclerosis, interstitial fibrosis, glomerular inflammation
      as well as decreased creatinine-clearance. This result was due to a markedly
      increased fraction of glomeruli with a defective glomerular architecture in the
      everolimus group. Everolimus apparently inhibited the chronic glomerular repair
      reaction via inhibition of the proliferative but not apoptotic activity of the
      glomerular endothelial and mesangial cells, which was associated with reduced
      glomerular vascular endothelial growth factor mRNA and protein. In contrast, the
      fraction of glomeruli with an intact glomerular architecture within the
      everolimus group showed clearly less glomerular enlargement compared to vehicle
      treated nephrectomy rats. CONCLUSION: This study demonstrates potential
      mechanisms of mTOR inhibitor induced renal deterioration and proteinuria in the
      low nephron number remnant kidney model.

PMID- 18091527
TI  - Depletion of LAG-3 positive cells in cardiac allograft reveals their role in
      rejection and tolerance.
AB  - BACKGROUND: Lymphocyte-activated gene-3 (LAG-3, CD223) is upregulated during the
      early stages of T-cell activation and could be the target of cytotoxic antibodies
      for induction therapy in transplantation. METHODS: Fully vascularized heterotopic
      allogeneic heart transplantation was performed in rats across a full major
      histocompatibility complex-mismatch barrier (LEW.1W into LEW.1A). Recipients
      received two injections (day 0 and 3) of cytotoxic antibodies directed to the
      extra-loop of LAG-3 immunoglobulin (Ig)-like N-terminal domain or control
      antibodies. RESULTS: LAG-3 mRNA transcripts accumulated in cardiac allografts
      undergoing rejection, but not in peripheral lymphoid organs. Administration of
      anti-LAG-3 antibodies on the day of transplantation did not modify alloreactivity
      of T lymphocytes from the spleen and did not change the alloantibody response.
      However, it inhibited graft infiltration by effector mononuclear cells, reduced
      intragraft levels of interferon-gamma mRNA and prolonged allograft survival from
      6 days in controls to a median of 27 days. Anti-LAG-3 antibodies were also active
      in prolonging survival when administered in a delayed manner, after rejection
      onset. LAG-3 being also expressed by activated regulatory T (Treg) cells, we
      tested the effect of anti-LAG-3 antibodies on graft acceptance after donor blood
      transfusions, a Treg-dependent tolerance induction model. We found that tolerance
      induction was prevented by anti-LAG-3 antibodies. CONCLUSIONS: Targeting LAG-3
      positive cells with cytotoxic antibodies is immunosuppressive in transplantation
      by depleting effectors T cells and therefore may represent a treatment for
      rejection episodes focused only on pathogenic cells. However, it might not be
      compatible with tolerance-induction strategies.

PMID- 18091528
TI  - Disparate host response and donor survival after the transplantation of
      mesenchymal or neuroectodermal cells to the intact rodent brain.
AB  - BACKGROUND: To circumvent ethical and legal complications associated with
      embryonic cell sources, investigators have proposed the use of nonneural donor
      sources for use in neural transplantation strategies. Leading candidate sources
      include autologous marrow stromal cells (MSCs) and fibroblasts, which are
      mesodermal derivatives. However, we recently reported that MSCs transplanted to
      the adult brain are rapidly rejected by an inflammatory response. Whether
      extrinsic variables or intrinsic mesenchymal traits stimulated inflammation and
      rejection is unknown. To determine the future utility of these cells in neural
      transplantation, we have now performed a systematic analysis of MSC
      transplantation to the brain. METHODS: To examine the effects of extrinsic
      variables on transplantation, green fluorescent protein (GFP)-expressing rat
      MSCs, cultured under distinct conditions, were transplanted stereotactically to
      the normal adult rat striatum, and donor survival and the host response was
      compared. To examine whether intrinsic donor traits promoted rejection, 50,000
      GFP-expressing rat MSCs, fibroblasts, or astrocytes were transplanted
      stereotactically to the adult rat striatum and graft survival and the host
      response was compared. RESULTS: Irrespective of preoperative culture conditions,
      MSCs elicited an inflammatory response and were rejected by 14 days, indicating
      acute rejection was not mediated by culture conditions. Comparison of MSC,
      fibroblast, or astrocyte grafts revealed that mesenchymal derivatives, MSCs and
      fibroblasts, elicited an inflammatory response and were rapidly rejected, whereas
      neuroectodermal astrocytes demonstrated robust survival in the absence of
      inflammation. CONCLUSIONS: Our findings suggest that intrinsic characteristics of
      mesenchymal cells may stimulate host inflammation, and thus may not represent an
      ideal donor source for transplantation to the adult brain.

PMID- 18091530
TI  - KIR/HLA ligand incompatibility in kidney transplantation.
AB  - BACKGROUND: The polymorphic family of killer-cell immunoglobulin-like receptors
      (KIRs) consists of activating and inhibitory receptors expressed by natural
      killer (NK) cells and effector T cells that recognize human leukocyte antigen
      (HLA) class I ligands. It has been suggested that KIR/HLA incompatibility exerts
      beneficial effects in hematopoietic stem cell transplantation. METHODS: To
      elucidate whether certain receptor-ligand combinations between recipient KIR and
      donor HLA antigens lead to enhanced alloreactivity of NK cells associated with
      acute rejection (aRx) after kidney transplantation, we analyzed the entirety of
      matches/mismatches between KIR genes and known HLA ligands for aRx patients
      (n=105) compared to patients with stable renal function (n=119). RESULTS: Whereas
      HLA-C ligand incompatibility between donor and recipient has no influence on aRx,
      grafts derived from donors homozygous for HLA-C group 2 alleles seem to
      demonstrate a better outcome (P=0.052). Additionally, a higher number of
      inhibitory receptors in the recipient's genotype (P=0.042), a significant higher
      number of matches for the receptors KIR2DL2/DS2 (P=0.004), as well as a higher
      number of mismatches for KIR2DL3 (P=0.014) could be observed for patients with
      stable renal function. CONCLUSION: Our data illustrate that certain KIR/HLA class
      I ligand combinations between donor and recipient might influence graft short
      term outcome after renal transplantation.

PMID- 18091529
TI  - Triptolide, a component of Chinese herbal medicine, modulates the functional
      phenotype of dendritic cells.
AB  - BACKGROUND: Triptolide (TPT) is a component of the Chinese herb Triptergium
      wilfordii and has potent immunosuppressive and anti-inflammatory effects. Since
      dendritic cells (DCs) play a critical role in the initiation of alloimmune
      responses to foreign grafts, the aim of the present study was to evaluate the
      effects of TPT in the functional phenotype of bone marrow (BM)-derived DCs.
      METHODS: BM-derived DCs were cultured with or without TPT from days 2 to 7 and
      then stimulated with lipopolysaccharide (LPS) for a further 2 days. In some
      experiments, TPT was added to the cultures from day 7 to day 9. Heterotopic
      cardiac transplantation was performed and animals received either no treatment or
      were injected systemically with different doses of TPT posttransplantation.
      RESULTS: TPT treatment inhibited LPS-induced DC maturation. The ability of DCs to
      stimulate allogeneic T-cell responses was also impaired by TPT treatment and
      accompanied by upregulated synthesis of interleukin-10 facilitating the expansion
      of regulatory T cells. Furthermore, we observed that TPT treatment led to
      increased cell surface expression of DC-SIGN and reduced expression of TLR4 on
      DCs. CONCLUSIONS: These findings demonstrate that TPT can inhibit the maturation
      and allogenicity of DCs and promotes the expansion of regulatory T cells. These
      effects were confirmed by in vivo experiments though treatment of TPT can prolong
      mice heart allograft survival. Furthermore, modulation of the DC surface
      phenotype towards that of a tolerogenic phenotype could contribute to the ability
      of TPT to suppress productive immunity and maintain homeostasis.

PMID- 18091531
TI  - A quantitative assay for Epstein-Barr Virus-specific immunity shows interferon
      gamma producing CD8+ T cells increase during immunosuppression reduction to treat
      posttransplant lymphoproliferative disease.
AB  - Reduction of immunosuppression (RIS) to allow development or recovery of Epstein
      Barr virus (EBV) immunity can be used to treat EBV-associated posttransplant
      lymphoproliferative disease (PTLD). Quantification of EBV-specific immunity would
      help assessment of the efficacy of RIS therapy. Use of intracellular cytokine
      staining and analysis by flow cytometry to monitor functional EBV-specific T-cell
      immunity was evaluated in healthy volunteers. The technique was then used to
      monitor EBV immunity in nine renal transplant patients with PTLD during RIS. The
      number of interferon (IFN)-gamma producing CD8+ T cells specific for EBV
      increased distinctly before regression of EBV+ PTLD tumors occurred. The findings
      confirm the importance of IFN-gamma producing CD8+ T cells in controlling the
      malignant EBV-transformed B cells of PTLD. The assay effectively quantified EBV
      immunity during RIS in transplant patients with PTLD.

PMID- 18091532
TI  - Quantitation of alloantibody concentration can predict patient sensitivity to
      intravenous immunoglobulin desensitization.
AB  - Despite the success of intravenous immunoglobulin (IVIg) desensitization to
      reduce anti-human leukocyte antigen antibodies, its high failure rate and expense
      limit its usefulness. We speculated that quantitation of alloantibody
      concentration could allow early identification of IVIg resistant patients.
      Patients were described as nonresponders (n=3) or responders (n=8). Panel
      reactive antibodies (PRA) were determined using Flowbeads and concentration
      calculated as molecules of equivalent soluble fluorochrome (MESF). PRA was
      equivalent between nonresponders and responders before (97+/-3% vs. 76+/-20%,
      P=NS) and after 3 IVIg/plasmapheresis (PP) treatments but lower among responders
      at end-of-treatment (76+/-20% vs. 44+/-15%, P<0.01). In contrast, pretreatment
      MESFs were higher (333,640+/-241,352 vs. 38,741+/-5,133, P=0.006) among
      nonresponders than responders. During treatment, MESFs decreased (P<0.05) in 0 of
      3 nonresponders vs. 8 of 8 responders. Final MESFs were higher among
      nonresponders than responders. We report that quantitation of MESFs allows early
      identification of IVIg/PP resistant patients. This sensitive and inexpensive
      technique should allow more effective patient selection and reduce the costs
      associated with desensitization.

PMID- 18091533
TI  - Bacteremic sepsis disturbs alveolar perfusion distribution in the lungs of rats.
AB  - OBJECTIVE: Sepsis often leads to lung injury, although the mechanisms that
      initiate this are unclear. One preinjury phenomenon that has not been explored
      previously is the effect of bacterial (nonlipopolysaccharide) sepsis on the
      distribution of alveolar perfusion. The goals of our studies were to measure
      this. DESIGN: Randomized, controlled, prospective animal study. SETTING:
      University animal laboratory. SUBJECTS: Male Sprague-Dawley rats (450-550 g).
      INTERVENTIONS: We induced sepsis by placing gelatin capsules containing
      Escherichia coli and Bacteroides fragilis into the abdomens of rats (n = 9).
      Empty capsules (n = 6) were placed into the abdomens of controls. After 24 hrs, 4
      microm-diameter fluorescent latex particles (2 x 10(8)) were infused into the
      pulmonary circulation. Sepsis was induced in additional rats and controls to
      assess lung injury, as follows: Lung histology was performed on eight septic rats
      and on seven controls; lung lavage was performed on three septic rats and three
      controls after their plasma albumin had been labeled with Evans blue dye.
      MEASUREMENTS AND MAIN RESULTS: Confocal microscopy was used to prepare digital
      maps of latex particle trapping patterns (eight per lung). Analysis of these
      patterns revealed statistically more clustering (perfusion inhomogeneity) down to
      tissue volumes less than that of ten alveoli in septic lungs compared with
      controls (p < or = .05). Bacterial counts and neutrophil counts were
      significantly higher in the circulation of septic rats (p < or = .05). Blood
      pressures and arterial PO2s were unchanged. Cell counts in histological images
      were three-fold higher in septic lungs than in controls (p < or = .05). Lung
      lavage revealed 0.41 +/- 0.03 mL of plasma in the lungs of septic rats, and 0.06
      +/- 0.05 mL in the lungs of controls (p < or = .05). CONCLUSIONS: Bacterial
      sepsis caused significant maldistribution of interalveolar perfusion in the lungs
      of rats in the absence of significant lung injury.

PMID- 18091534
TI  - Gas exchange impairment induced by open suctioning in acute respiratory distress
      syndrome: impact of permissive hypercapnia.
AB  - OBJECTIVE: To determine whether hypercarbia occurs following the use of open
      suctioning in lung lavage injured sheep and whether the baseline PaCO2 and
      duration of suctioning affect gas exchange. DESIGN: Prospective laboratory
      evaluation. SETTING: Animal laboratory in a university hospital. SUBJECTS: Seven
      female Dorset sheep. INTERVENTIONS: Lung lavage was used to create acute
      respiratory distress syndrome (ARDS). Mechanical ventilation was provided to
      produce different baseline PaCO2 levels. MEASUREMENTS AND MAIN RESULTS: Lung
      injury was developed by isotonic saline lavage until the PaO2 decreased to 100
      150 mm Hg on an FIO2 of 1.0, positive end-expiratory pressure (PEEP) 5 cm H2O,
      and tidal volume 10 mL/kg. Then tidal volume was decreased to 6 mL/kg. Open
      suctioning was performed on each animal. Each animal experienced four
      experimental conditions in random order (PaCO2 40 and 80 mm Hg and duration of
      suctioning 10 and 30 secs). Before each of the four experimental conditions,
      animals underwent lung recruitment continuous positive airway pressure 40 cm H2O
      for 40 secs to normalize volume history followed by ventilation for 15 mins where
      FIO2 and PEEP were set based on the ARDSNet FIO2/PEEP. Mean arterial blood
      pressure, heart rate, pulmonary artery pressure, pulmonary artery occlusion
      pressure, cardiac output, and arterial blood gases were measured before, 1 min
      after, and then every 2 mins after open suctioning for 30 mins. Neither the
      duration of suctioning nor the baseline level of CO2 had an important influence
      on the magnitude of the desaturation and the recovery of PO2 following suctioning
      (p < .05). Level of PEEP did influence the recovery of PaO2 following suctioning.
      CONCLUSIONS: While neither baseline CO2 nor duration of suctioning affected the
      gas exchange alterations induced by endotracheal suction, high levels of PEEP can
      help to avoid the associated gas exchange abnormalities in ARDS.

PMID- 18091535
TI  - Characteristics and outcomes of patients receiving a medical emergency team
      review for acute change in conscious state or arrhythmias.
AB  - OBJECTIVE: To describe the characteristics and outcomes of patients receiving a
      medical emergency team (MET) review for the MET syndromes of acute change in
      conscious state or arrhythmia and to assess the effect of delayed MET activation
      on their outcomes. DESIGN: Retrospective analysis of medical records. SETTING:
      University teaching hospital. PATIENTS: Two cohorts of 100 patients for each of
      the MET syndromes of acute change in conscious state or arrhythmia.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected information on
      patient demographics, comorbidities, and presence of sepsis, hypovolemia,
      cardiogenic shock, and patient outcome. We also documented the presence and
      duration of delayed MET activation. The median age for both syndromes was >70
      yrs, and major comorbidities were present in >10% of patients. A history of
      ischemic heart disease (p < .001) and congestive cardiac failure (p = .007) was
      more common in patients with arrhythmias. Cardiogenic shock and sepsis were
      common underlying causes of the MET calls for the two groups. However,
      cardiogenic shock was more common in patients with arrhythmias (p < .001).
      Hospital mortality was 35% for patients with an acute change in conscious state,
      compared with 18% for patients with arrhythmias (p = .01). Delayed MET activation
      occurred in 35% of acute change in conscious state patients and in 24% of
      arrhythmia patients (p = .09) with a median duration of delay of 16 and 13 hrs,
      respectively. Delayed MET activation was associated with increased mortality
      (odds ratio 3.1, 95% confidence interval 1.4-6.6, p = .005). CONCLUSIONS: An
      acute change in conscious state leading to a MET call carried a greater risk of
      death than activation due to arrhythmias. Delayed activation was common for both
      syndromes and was independently associated with an increased risk of death.

PMID- 18091536
TI  - Effects of hypertonic/hyperoncotic treatment and surgical evacuation after acute
      subdural hematoma in rats.
AB  - OBJECTIVE: The treatment of acute subdural hematoma (ASDH) consists mainly of
      surgical evacuation of the hematoma. It is conceivable that early preoperative
      neuroprotection with hypertonic/hyperoncotic treatment (HHT) can improve survival
      rates. The present study investigated the benefit of treatment with
      hypertonic/hyperoncotic solution on functional and histologic outcome as
      supportive therapy accompanying surgical intervention. DESIGN: Laboratory
      experiment. SETTING: University laboratory. SUBJECTS: Male Sprague-Dawley rats
      weighing 296-350 g (n = 56). INTERVENTIONS: ASDH was induced through subdural
      infusion of 400 microL of autologous venous blood. Thirty minutes after subdural
      blood infusion, the rats received either HyperHAES (7.2% saline/6% hydroxyethyl
      starch) or vehicle (NaCl 0.9%) intravenously, followed by surgical evacuation of
      the hematoma 1 hr after ASDH induction in those rats scheduled for surgical
      treatment. The experiment was divided into two parts: an acute study, which
      explored acute effects of HHT on blood variables, ASDH-induced changes of
      intracranial pressure (ICP), and cerebral perfusion pressure (CPP), and a chronic
      study, which investigated the chronic effects of HHT, surgical blood clot
      evacuation, and the combination of both on the functional and histologic outcome
      following ASDH (12 days). MEASUREMENTS AND MAIN RESULTS: In the acute study, HHT
      expectedly raised the serum sodium concentration and lowered hematocrit. ASDH
      increased ICP and decreased CPP in all groups. HHT improved CPP by reducing ICP.
      In the chronic study, all treated groups showed a better recovery with respect to
      neurologic function and neuronal cell death compared with the vehicle-treated
      ASDH group. HHT with surgical evacuation or HHT alone improved functional and
      histologic outcome slightly more than surgical evacuation alone. CONCLUSIONS: In
      this rat model, HHT led to a decrease of ICP after ASDH. This significantly
      improved functional and histologic outcome, which was comparable to the effects
      after blood evacuation alone. The combination of evacuation of subdural blood and
      early HHT improved histologic outcome further but not significantly, which was
      due to the strong effects of single treatments and a ceiling effect of the
      combined treatment in this model.

PMID- 18091537
TI  - Pharmacologic cholinesterase inhibition improves survival in experimental sepsis.
AB  - OBJECTIVE: Lethal sepsis occurs when an excessive inflammatory response evolves
      that cannot be controlled by physiologic anti-inflammatory mechanisms, such as
      the recently described cholinergic anti-inflammatory pathway. Here we studied
      whether the cholinergic anti-inflammatory pathway can be activated by
      pharmacologic cholinesterase inhibition in vivo. DESIGN: Prospective, randomized
      laboratory investigation that used an established murine sepsis model. SETTING:
      Research laboratory in a university hospital. SUBJECTS: Female C57BL/6 mice.
      INTERVENTIONS: Sepsis in mice was induced by cecal ligation and puncture. Animals
      were treated immediately with intraperitoneal injections of nicotine (400
      microg/kg), physostigmine (80 microg/kg), neostigmine (80 microg/kg), or solvent
      three times daily for 3 days. MEASUREMENTS AND MAIN RESULTS: Treatment with
      physostigmine significantly reduced lethality (p < or = .01) as efficiently as
      direct stimulation of the cholinergic anti-inflammatory pathway with nicotine (p
      < or = .05). Administration of cholinesterase inhibitors significantly down
      regulated the binding activity of nuclear factor-kappaB (p < or = .05) and
      significantly reduced the concentration of circulating proinflammatory cytokines
      tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 (p < or =
      .001), and pulmonary neutrophil invasion (p < or = .05). Animals treated with the
      peripheral cholinesterase inhibitor neostigmine showed no difference compared
      with physostigmine-treated animals. CONCLUSIONS: Our results demonstrate that
      cholinesterase inhibitors can be used successfully in the treatment of sepsis in
      a murine model and may be of interest for clinical use.

PMID- 18091538
TI  - Validation of the Mortality in Emergency Department Sepsis (MEDS) score in
      patients with the systemic inflammatory response syndrome (SIRS).
AB  - OBJECTIVE: To prospectively and externally validate the Mortality in Emergency
      Department Sepsis (MEDS) score as a predictor of 28-day mortality in patients who
      present to the emergency department with a systemic inflammatory response
      syndrome. DESIGN: Multicentered prospective cohort study. SETTING: Emergency
      departments at the University of Colorado Hospital and Denver Health Medical
      Center in Denver, CO, and Albert Einstein Medical Center and the Hospital of the
      University of Pennsylvania in Philadelphia, PA. SUBJECTS: Adult patients who
      presented to the emergency department, who met criteria for systemic inflammatory
      response syndrome, and who were admitted to the hospital. MEASUREMENTS: The MEDS
      score was calculated by recording the presence of terminal illness, tachypnea or
      hypoxemia, septic shock, platelet count <150,000 cells/mm3, band count as a
      percentage of total white blood cell count >5%, age >65 yrs, lower respiratory
      infection, nursing home residence, and altered mental status. OUTCOME: Mortality
      within 28 days or discharged alive from the hospital. RESULTS: In all, 385
      patients were enrolled between 18 and 100 yrs of age. The overall mortality was
      9%. As in the original article, the MEDS score was categorized into five groups:
      very low, low, moderate, high, and very high for 28-day mortality. Mortality
      rates for each group were 0.6% (95% confidence interval [CI], 0%-3%), 5% (95% CI,
      1%-13%), 19% (95% CI, 11%-29%), 32% (95% CI, 15%-54%), and 40% (95% CI, 12%-74%),
      respectively. The MEDS score had an area under the receiver operating
      characteristic curve of 0.88 (95% CI, 0.83-0.92). CONCLUSIONS: The MEDS score
      accurately predicts 28-day mortality in patients who present to the emergency
      department with systemic inflammatory response syndrome and who are admitted to
      the hospital.

PMID- 18091539
TI  - How decisions are made to admit patients to medical intensive care units (MICUs):
      a survey of MICU directors at academic medical centers across the United States.
AB  - OBJECTIVE: To determine how medical intensive care unit (MICU) admission
      decisions are made at U.S. academic MICUs and to learn how these practices
      compare with the recommendations of the Society of Critical Care Medicine and the
      American Thoracic Society. DESIGN: A 22-question Web-based survey. SETTING:
      University health sciences centers. SUBJECTS: MICU directors at academic U.S.
      medical centers offering fellowship programs in pulmonary/critical care or
      critical care medicine. INTERVENTIONS: The survey was sent by E-mail to 146
      academic MICU directors. MEASUREMENTS AND MAIN RESULTS: Survey response rate was
      83% (121/146). MICU attendings were the primary decision-maker for patient
      admission to the intensive care unit (ICU) in 40% of the MICUs during daytime
      hours, in 36% on weekends, and in 27% overnight. Critical care fellows and
      resident house staff were often responsible for making MICU admission decisions,
      particularly overnight and on weekends. Of the MICUs surveyed, 88% had written
      admission guidelines, although only 25% used them on a regular basis. Written
      restriction guidelines were present in only 21% of these ICUs, although 53% of
      MICU directors believed that MICUs should have standardized criteria for
      restricting admission to the ICU. Finally, 29% of MICUs surveyed did not
      authorize MICU attendings to deny ICU admission on a case-by-case basis for
      futile or inadvisable care, thereby maintaining an open door policy for ICU
      admission. CONCLUSIONS: Significant practice variability exists across U.S.
      academic MICUs regarding how decisions are made to admit patients to the ICU. The
      majority of academic MICUs in the United States do not strictly employ ICU
      admission and restriction guidelines, as recommended by the Society of Critical
      Care Medicine and the American Thoracic Society.

PMID- 18091540
TI  - Noninvasive positive-pressure ventilation in acute respiratory failure outside
      clinical trials: experience at the Massachusetts General Hospital.
AB  - BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) has been shown to be
      effective in select patients enrolled in clinical trials. However, few data are
      available on the use of NPPV as routine standard medical care for patients with
      respiratory failure outside of controlled trials. MEASUREMENTS AND MAIN RESULTS:
      All patients receiving NPPV for a 1-yr period for acute or acute on chronic
      respiratory failure who did not select do not intubate/resuscitate status were
      evaluated. Demographic, physiological, and laboratory data were collected for as
      long as NPPV was provided. Data were recorded on 449 patients. Intubation rate
      was 18%, 24%, 38%, 40%, and 60%, respectively, for patients with cardiogenic
      pulmonary edema (n = 97), acute exacerbation of chronic obstructive pulmonary
      disease (n = 87), non-chronic obstructive pulmonary disease acute hypercapnic
      respiratory failure (n = 35), postextubation respiratory failure patients (n =
      95), and acute hypoxemic respiratory failure (n = 144). The hospital mortality
      for patients with acute hypoxemic respiratory failure who failed NPPV was 64%. A
      logistic regression showed that baseline Simplified Acute Physiology Score II
      (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.05-1.10; p <.0001),
      Glasgow Coma Scale (OR, 0.76; 95% CI, 0.66-0.87; p <.0001), PaO2/FIO2 ratio (OR,
      0.98; 95% CI, 0.93-0.99; p = .02), and serum albumin (OR, 0.30; 95% CI, 0.16
      0.57; p < .001) were the variables associated with NPPV failure. CONCLUSION: NPPV
      as routine standard medical care resulted in the intubation of a similar
      percentage of patients with respiratory failure due to cardiogenic pulmonary
      edema and chronic obstructive pulmonary disease exacerbation as shown in
      randomized controlled trials but in a higher percent of patients with hypoxemic
      respiratory failure than reported in these trials. NPPV failure was associated
      with high hospital mortality for patients with hypoxemic respiratory failure.

PMID- 18091541
TI  - Venous thrombosis in patients with short- and long-term central venous catheter
      associated Staphylococcus aureus bacteremia.
AB  - OBJECTIVE: Infection and thrombosis are important complications of intravascular
      catheters. The purpose of this study was to determine the incidence of thrombosis
      in patients with central venous catheter-associated Staphylococcus aureus
      bacteremia and the utility of physical examination for diagnosing upper extremity
      or neck venous thrombosis. DESIGN: Prospective observational cohort. SETTING:
      Tertiary care facility. PATIENTS: In all, 65 consecutive patients with catheter
      associated S. aureus bacteremia with central venous catheters of the internal
      jugular, brachial, or subclavian veins were eligible for participation.
      INTERVENTION: From July 1999 through August 2004, enrolled patients underwent
      physical examination and ultrasonography independently to identify the presence
      of catheter-associated thrombosis. Study ultrasonograms were interpreted blindly
      using defined criteria. Outcomes were defined at 12-wk follow-up. MEASUREMENTS
      AND MAIN RESULTS: A total of 48 patients were enrolled. By ultrasonography,
      definite or possible thrombosis was present in 34 of 48 patients (71%) in this
      cohort. Death or recurrent bacteremia occurred in 11/34 (32%) infected patients
      with thrombosis and two of 14 (14%) infected patients without thrombosis (p =
      .29). Sensitivity of all physical examination findings, either alone or in
      combination, was low (< or = 24%). Only engorged veins upon hand elevation and
      the presence of multiple physical examination abnormalities were specific (100%
      each). CONCLUSIONS: Thrombosis is a common complication of central venous
      catheter-associated S. aureus bacteremia. Patients with central venous catheter
      associated S. aureus bacteremia should undergo ultrasonography to detect
      thromboses even if the physical examination is normal.

PMID- 18091542
TI  - Acute phase response impairs host defense against Pseudomonas aeruginosa
      pneumonia in mice.
AB  - OBJECTIVE: Pseudomonas aeruginosa is a common pathogen in hospital-acquired
      pneumonia. Especially trauma and postsurgical patients display a profound acute
      phase protein response and are susceptible to acquiring pneumonia. The objective
      was to study the influence of the acute phase response induced by sterile tissue
      injury on pulmonary host defense. DESIGN: Laboratory investigation. SETTING:
      Academic medical center. SUBJECTS: Female C57Bl/6 wild-type mice, 8-10 wks old.
      INTERVENTIONS: Mice were injected subcutaneously with either turpentine or
      sterile saline (control) in both hind limbs 1 day before intranasal infection
      with P. aeruginosa. MEASUREMENTS AND MAIN RESULTS: The turpentine-induced acute
      phase response was associated with 100% lethality after induction of pneumonia,
      whereas control mice all survived the Pseudomonas infection. In addition,
      turpentine-injected mice demonstrated much higher bacterial loads in their lungs
      and an increased dissemination of the infection. The acute phase reaction
      attenuated lung inflammation during pneumonia, as reflected by histopathology,
      reduced pulmonary levels of proinflammatory cytokines, and a strongly diminished
      recruitment of neutrophils to the site of infection. Blood neutrophils harvested
      from turpentine injected mice displayed a reduced capacity to up-regulate their
      CD11b/CD18 expression upon stimulation with Pseudomonas ex vivo and during
      Pseudomonas pneumonia in vivo. Administration of a blocking anti-CD11b antibody
      to turpentine-injected and control mice almost completely abrogated the
      difference in bacterial outgrowth, whereas inhibition of the sympathetic nervous
      system did not affect the impaired pulmonary host defense in mice with an acute
      phase response. CONCLUSIONS: These data suggest that a systemic acute phase
      response might impair host defense against P. aeruginosa pneumonia, possibly in
      part by inhibition of CD11b/CD18-dependent neutrophil recruitment.

PMID- 18091543
TI  - Detecting ineffective triggering in the expiratory phase in mechanically
      ventilated patients based on airway flow and pressure deflection: feasibility of
      using a computer algorithm.
AB  - OBJECTIVE: Ineffective triggering (IT) is the most common manifestation of
      patient-ventilator asynchrony in mechanically ventilated patients. IT in the
      expiratory phase (ITE) accounts for the majority of IT and is associated with
      characteristic features of flow and airway pressure deflection, caused by
      ineffective effort from the patient. The purpose of this study was to quantify
      the characteristics of flow and airway pressure deflections of ITE and, using a
      computerized algorithm, to evaluate their usefulness in the detection of ITEs.
      DESIGN: Prospective, clinical study. SETTING: Medical intensive care unit in a
      1,000-bed university hospital. PATIENTS: A total of 14 mechanically ventilated
      adult patients with patient-ventilator asynchrony. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: We analyzed 5,899 breaths and found that 1,831
      were ITEs. The average values for maximum flow deflection (F(def)) and maximum
      airway pressure deflection (P(def)) in ITEs were 13.94 +/- 8.0 L/min and 1.91 +/-
      0.97 cm H2O. With a starting value of 0.1 L/min for F(def) and 0.01 cm H2O for
      P(def), the area under the receiver operating characteristics curve of F(def) and
      P(def) for the detection of ITEs was 0.98 and 0.97, respectively. Sensitivity and
      specificity for the detection of ITEs were 91.5% and 96.2% for F(def),
      respectively, for a cutoff value of 5.45 L/min, and 93.3% and 92.9% for Pdef, for
      a cutoff value of 0.45 cm H2O. CONCLUSION: We conclude that accurately detecting
      and quantifying ITEs is feasible using a computerized algorithm based on F(def)
      and P(def). Such a computerized estimation of patient-ventilator interaction
      might be helpful for adjusting ventilator settings in an intensive care unit.

PMID- 18091544
TI  - Poly(ADP-ribose) polymerase-1 inhibition increases expression of heat shock
      proteins and attenuates heat stroke-induced liver injury.
AB  - OBJECTIVE: Heat stroke is a life-threatening illness characterized by an
      increased core body temperature as a result of exposure to high ambient
      temperature. Despite advances in supportive care, heat stroke is often fatal, and
      no specific and effective therapies exist. The pathophysiological responses to
      heat stroke involve a systemic inflammatory response and a disseminated
      intravascular coagulation in the host, which lead to a multiorgan dysfunction
      syndrome. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear DNA-binding protein
      that has been shown to play a relevant role in cell necrosis and organ failure in
      various diseases associated with inflammation. Therefore, we set out to
      investigate whether inhibition of PARP activity might affect the heat stroke
      induced injury. DESIGN: Controlled animal study. SETTING: Research laboratory of
      an academic institution. SUBJECTS: PARP-1-deficient mice (Parp-1(-/-)) and wild
      type mice (C57BL/6J). INTERVENTIONS: Wild-type mice untreated or treated with
      either PJ34 or 3-AB, two generic PARP inhibitors, and Parp-1(-/-) mice were
      subjected to heat exposure as a model to study heat stroke. MEASUREMENTS AND MAIN
      RESULTS: We measured rectal temperature, serum interleukin-1beta and interleukin
      6, liver histology, and heat shock proteins expression. We found that the heat
      stroke-induced injury was attenuated in mice lacking PARP-1 and was markedly
      reduced in wild-type mice treated with PARP inhibitors. Interestingly, heat
      induced expression of heat shock proteins 27 and 70 was boosted after PARP
      inhibition. Indeed, PARP inhibition increased expression of heat shock proteins
      27 and 70 even in the absence of heat exposure. Accordingly, PARP inhibition
      increased thermal tolerance that may contribute to attenuate the clinical effects
      of heat stroke, resulting in increased survival. CONCLUSIONS: Our results find a
      new protective function of PARP inhibitors and support their potential
      therapeutic application in the treatment of heat stroke.

PMID- 18091546
TI  - Critical role of p38 mitogen-activated protein kinase signaling in septic lung
      injury.
AB  - OBJECTIVE: Leukocyte-mediated tissue damage is a key feature in septic lung
      injury, although the signaling mechanisms behind pulmonary recruitment of
      leukocytes remain elusive. The aim of the present study was to define the role of
      p38 mitogen-activated protein kinase (MAPK) signaling in septic lung injury.
      DESIGN: Prospective experimental study. SETTING: University hospital research
      unit. SUBJECTS: Male C57BL/6 mice. INTERVENTIONS: Pulmonary edema,
      bronchoalveolar infiltration of leukocytes, levels of myeloperoxidase, and CXC
      chemokines were determined 6 and 24 hrs after cecal ligation and puncture (CLP).
      The specific p38 MAPK inhibitors SB 239063 and SKF 86002 were given immediately
      before CLP induction. Phosphorylation and activity of p38 MAPK were determined by
      immunoprecipitation and Western blot. MEASUREMENTS AND MAIN RESULTS: CLP induced
      clear-cut pulmonary damage characterized by edema formation, leukocyte
      infiltration, and increased levels of CXC chemokines in the lung. Moreover, CLP
      increased phosphorylation and activity of p38 MAPK in the lung, which was
      markedly inhibited by SB 239063. Interestingly, inhibition of p38 MAPK signaling
      protected against CLP-induced lung damage and edema. Indeed, both SB 239063 and
      SKF 86002 decreased CLP-induced leukocyte recruitment in the bronchoalveolar
      space and formation of CXC chemokines in the lung. CONCLUSIONS: Our data
      demonstrate that p38 MAPK signaling constitutes a key role in regulating CXC
      chemokine production in septic lung injury and that inhibition of p38 MAPK
      activity abolishes pulmonary infiltration of leukocytes as well as lung edema.
      These novel findings suggest that targeting the p38 MAPK signaling pathway may
      pave the way for a new therapeutic strategy against lung injury in polymicrobial
      sepsis.

PMID- 18091545
TI  - Randomized trial of combination versus monotherapy for the empiric treatment of
      suspected ventilator-associated pneumonia.
AB  - OBJECTIVE: To compare a strategy of combination therapy with a strategy of
      monotherapy with broad-spectrum antibiotics for suspected late ventilator
      associated pneumonia. DESIGN: Randomized trial. SETTING: Twenty-eight intensive
      care units in Canada and the United States. PATIENTS: The study included 740
      mechanically ventilated patients who developed suspected ventilator-associated
      pneumonia after 96 hrs in the intensive care unit. Patients known to be colonized
      or infected with Pseudomonas or methicillin-resistant Staphylococcus aureus or
      who were immunocompromised were excluded from the study. INTERVENTIONS: As
      initial unblinded therapy, patients were allocated to receive meropenem (1 g
      every 8 hrs) and ciprofloxacin (400 mg every 12 hrs) or meropenem alone. Before
      starting antibiotics, patients were also randomized to bronchoalveolar lavage
      with quantitative cultures or endotracheal aspirates. When culture results were
      available, physicians were encouraged to adjust antibiotics. Adequacy of
      antibiotics was defined as the organism present in the enrollment culture having
      in vitro susceptibility to one or more of the study antibiotics. MEASUREMENTS AND
      MAIN RESULTS: Baseline characteristics and etiologies of ventilator-associated
      pneumonia were similar in the two groups. There was no difference in 28-day
      mortality between the combination and monotherapy groups (relative risk = 1.05,
      95% confidence interval 0.78-1.42, p = .74). Duration of intensive care unit and
      hospital stay, clinical and microbiological treatment response, emergence of
      antibiotic-resistant bacteria, isolation of Clostridium difficile in stool, and
      fungal colonization were also similar in the two groups. In a subgroup of
      patients who had infection due to Pseudomonas species, Acinetobacter species, and
      multidrug-resistant gram-negative bacilli at enrollment (n = 56), the adequacy of
      initial antibiotics (84.2% vs. 18.8%, p < .001) and microbiological eradication
      of infecting organisms (64.1% vs. 29.4%, p = .05) was higher in the combination
      group compared with the monotherapy group, but there were no differences in
      clinical outcomes. CONCLUSIONS: For critically ill patients who have suspected
      late ventilator-associated pneumonia and who are at low risk for difficult-to
      treat gram-negative bacteria, monotherapy is associated with similar outcomes
      compared with combination therapy. For those patients at high risk of difficult
      to-treat gram-negative bacteria, combination therapy is safe and may be
      associated with better microbiological and clinical outcomes.

PMID- 18091547
TI  - Effects of changes in vascular tone on the agreement between pulse contour and
      transpulmonary thermodilution cardiac output measurements within an up to 6-hour
      calibration-free period.
AB  - OBJECTIVES: To examine whether the agreement between pulse contour and
      transpulmonary thermodilution cardiac index (CI) measurements is altered by
      changes in vascular tone within an up to 6-hr calibration-free period. DESIGN:
      Observational study. SETTING: Medical intensive care unit of a university
      hospital. PATIENTS: Fifty-nine critically ill patients. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Data from 59 critically ill patients equipped with
      a PiCCO device were retrospectively analyzed. The database contained the
      transpulmonary thermodilution CI (CI(T)) value obtained at each time point the
      device was calibrated and the pulse contour CI (CI(PC)) value recorded
      immediately before this time point. Seven subsets of CI pairs were defined
      according to intervals of time elapsed from the previous calibration (within the
      first 30 mins, between 30 mins and 1 hr, and every hour up to 6 hrs). In the
      whole set of 400 CI pairs, CI(PC) correlated with CI(T) (r2 = .68, p < .001). The
      bias +/- SD was 0.12 +/- 0.61 L/min/m2, and the percentage error was 35%. Among
      the seven time-interval subsets, the percentage error was <30% only in the two
      first ones (27% and 26%, respectively). When changes in systemic vascular
      resistance by >15% occurred (129 times), CI(PC) correlated with CI(T) (r2 = .64),
      the bias +/- SD was 0.12 +/- 0.62 L/min/m2, and the percentage error was 36%. In
      the subset of CI pairs recorded within the 1-hr calibration-free period while
      vascular resistance changed by >15% (n = 32), the bias +/- SD was 0.04 +/- 0.47
      L/min/m and the percentage error was 29%. CONCLUSIONS: Our study in critically
      ill patients suggests that the agreement between pulse contour cardiac output and
      transpulmonary thermodilution cardiac output was not significantly influenced by
      changes in vascular tone. However, after a 1-hr calibration-free period,
      recalibration may be encouraged. Such a procedure provides helpful information
      drawn from other thermodilution-derived variables.

PMID- 18091550
TI  - Lower hospital mortality and complications after pediatric hematopoietic stem
      cell transplantation.
AB  - OBJECTIVE: To assess protective and risk factors for mortality among pediatric
      patients during initial care after hematopoietic stem cell transplantation (HSCT)
      and to evaluate changes in hospital mortality. DESIGN: Retrospective cohort using
      the 1997, 2000, and 2003 Kids Inpatient Database, a probabilistic sample of
      children hospitalized in the United States with a procedure code for HSCT.
      SETTING: Hospitalized patients in the United States submitted to the database.
      PATIENTS: Age, <19 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Hospital mortality significantly decreased from 12% in 1997 to 6% in 2003. Source
      of stem cells changed with increased use of cord blood. Rates of sepsis, graft
      versus host disease, and mechanical ventilation significantly decreased. Compared
      with autologous HSCT, patients who received an allogenic HSCT without T-cell
      depletion were more likely to die (adjusted odds ratio, 2.4; 95% confidence
      interval, 1.5, 3.9), while children who received cord blood HSCT were at the
      greatest risk of hospital death (adjusted odds ratio, 4.8; 95% confidence
      interval, 2.6, 9.1). Mechanical ventilation (adjusted odds ratio, 26.32; 95%
      confidence interval, 16.3-42.2), dialysis (adjusted odds ratio, 12.9; 95%
      confidence interval, 4.7-35.4), and sepsis (adjusted odds ratio, 3.9; 95%
      confidence interval, 2.5-6.1) were all independently associated with death, while
      care in 2003 was associated with decreased risk (adjusted odds ratio, 0.4; 95%
      confidence interval, 0.2-0.7) of death. CONCLUSIONS: Hospital mortality after
      HSCT in children decreased over time as did complications including need for
      mechanical ventilation, graft versus host disease, and sepsis. Prevention of
      complications is essential as the need for invasive support continues to be
      associated with high mortality risk.

PMID- 18091548
TI  - Immunoglobulin G treatment of postcardiac surgery patients with score-identified
      severe systemic inflammatory response syndrome--the ESSICS study.
AB  - OBJECTIVE: A minority of patients develop severe systemic inflammatory response
      syndrome (SIRS) with high mortality following cardiopulmonary bypass-assisted
      cardiac surgery. We assessed whether intravenous immunoglobulin G (ivIgG)
      improves postoperative short-term (5-day) morbidity and reduces 28-day mortality
      in these patients. DESIGN: Randomized, double-blind, placebo-controlled,
      multicenter trial. SETTING: Intensive care units of 11 cardiothoracic centers.
      PATIENTS AND INTERVENTIONS: Of 6,984 patients screened, we identified 244 with
      severe SIRS (Acute Physiology and Chronic Health Evaluation II score > or = 28 on
      the first postoperative day). INTERVENTIONS: The 244 patients with severe SIRS
      were randomly assigned to receive an intravenous infusion of either albumin 0.1%
      (placebo group, 6 mL [6 mg]/kg of body weight on day 1 and 3 mL [3 mg]/kg of body
      weight on day 2) or immunoglobulin G 10% (ivIgG group, 6 mL [600 mg]/kg of body
      weight on day 1 and 3 mL [300 mg]/kg of body weight on day 2). MEASUREMENTS AND
      MAIN RESULTS: The prospectively defined primary end points were improvement in
      morbidity on day 5 and death from any cause assessed on day 28. A total of 218
      patients received both doses of the study drug (placebo n = 108, ivIgG n = 110).
      Acute Physiology and Chronic Health Evaluation II scores in the placebo group
      decreased from 31.8 +/- 4.0 (day 1) to 25.8 +/- 9.3 (day 5) and in the ivIgG
      group from 31.8 +/- 3.4 (day 1) to 25.9 +/- 10.3 (day 5), with no significant
      difference between the groups (p = .56). The 28-day mortality rate was not
      significantly different between the groups (per protocol population, placebo
      group 31.5%, ivIgG group 39.1%; intent-to-treat population, placebo group 37.2%,
      ivIgG group: 44.7%). No effect of ivIgG on plasma levels of interleukin-6, tumor
      necrosis factor, and tumor necrosis factor receptor I/II was observed. Drug
      related adverse events were rare in both groups. CONCLUSIONS: Patients undergoing
      cardiac surgery (involving cardiopulmonary bypass) who develop severe SIRS derive
      no improvement in short-term morbidity or 28-day mortality from ivIgG.

PMID- 18091551
TI  - Effects of the TREM-1 pathway modulation during mesenteric ischemia-reperfusion
      in rats.
AB  - OBJECTIVES: The triggering receptor expressed on myeloid cells (TREM)-1, a
      receptor expressed on the surface of neutrophils and monocytes/macrophages,
      synergizes with the Toll-like receptors in amplifying the inflammatory response
      mediated by microbial components. Because the pathogenesis of ischemia
      reperfusion-induced gastrointestinal tissue injury and multiple organ failure
      implies leukocyte activation and bacterial translocation, we hypothesized that
      the TREM-1 pathway modulation would prove beneficial in this setting. DESIGN:
      Animal study. SETTING: Research laboratory. SUBJECTS: Adult male Wistar rats (250
      300 g). INTERVENTIONS: Rats were subjected to intestinal ischemia-reperfusion
      induced by occlusion of the superior mesenteric artery during 60 mins and
      reperfused for 180 mins. At the time of reperfusion, animals were administered
      with LP17 (a synthetic TREM-1 inhibitor), a control peptide, or a vehicle (normal
      saline). Plasma concentrations of tumor necrosis factor-alpha, interleukin-6, and
      soluble TREM-1 were measured by enzyme-linked immunosorbent assay. Hepatic
      activation of the transcriptional factor nuclear factor-kappaB was assessed by
      electrophoretic mobility shift assay. Hepatic oxidant-antioxidant balance was
      estimated by measurement of lipid peroxidation and catalase activity. Ileal
      mucosal permeability was estimated by fluorescein dextran-4 clearance and
      bacterial translocation by mesenteric lymph nodes culture. MEASUREMENTS AND MAIN
      RESULTS: Ischemia-reperfusion was associated with cardiovascular collapse, lactic
      acidosis, and systemic and hepatic inflammatory response that were partly
      prevented by LP17 administration. Liver lipid peroxidation and catalase depletion
      were attenuated by LP17. Ischemia-reperfusion induced a marked increase in ileal
      mucosal permeability and an associated bacterial translocation that was also
      prevented by TREM-1 modulation. LP17 delayed mortality. CONCLUSIONS: The
      modulation of the TREM-1 pathway by the means of a synthetic peptide may be
      useful during acute mesenteric ischemia.

PMID- 18091552
TI  - Community meetings for emergency research community consultation.
AB  - OBJECTIVE: To survey attendees at community meetings for an emergency research
      protocol and determine whether these meetings aid participants' understanding and
      decision to support the proposed emergency research. DESIGN: Postmeeting
      questionnaire. SETTING: Three community meetings for the PolyHeme study in San
      Antonio area. SUBJECTS: One hundred fifty community meeting attendees.
      INTERVENTIONS: PolyHeme research team representatives made a study presentation
      concerning exception to informed consent regulations. In addition, institutional
      review board (IRB) members attended these meetings and made a separate
      presentation about the IRB approval of research and the exception to informed
      consent in emergency research. The IRB members requested attendees to voluntarily
      complete an additional Community Consultation Survey assessing demographics,
      community meeting satisfaction, and impact of the community meeting on their
      attitudes toward emergency research studies. MEASUREMENTS AND MAIN RESULTS:
      Feedback to the PolyHeme investigators with their validation questions indicated
      that 35% of the respondents objected to research without prior consent, but 82%
      gave approval for the study in the local community; 137 attendees completed the
      additional Community Consultation Survey. The average score on the adequacy of
      information provided about the PolyHeme study was 0.58 on a 5-point Likert scale
      (-2 to +2). Adequacy of IRB background information on human subjects research
      received an average score of 0.56, and the overall clarity of the information on
      community consultation was 0.91. Although 80% of respondents felt there was a
      potential benefit from PolyHeme, <67% would either want to participate or enroll
      their family members with or without prior consent. CONCLUSIONS: The majority of
      community meeting attendees understand basic concepts and regulations of
      emergency research without prior consent. Despite an 82% concurrence with the
      study in their community, approximately 30% of persons would not willingly choose
      to participate in emergency research or provide consent for their family members
      despite knowledge about the process.

PMID- 18091553
TI  - Effects of ventilation with 100% oxygen during early hyperdynamic porcine fecal
      peritonitis.
AB  - OBJECTIVE: Early goal-directed therapy aims at balancing tissue oxygen delivery
      and demand. Hyperoxia (i.e., pure oxygen breathing) has not been studied in this
      context, since sepsis increases oxygen radical production, which is believed to
      be directly related to the oxygen tension. On the other hand, oxygen breathing
      improved survival in various shock models. Therefore, we hypothesized that
      hyperoxia may be beneficial during early septic shock. DESIGN: Laboratory animal
      experiments. SETTING: Animal research laboratory at university medical school.
      SUBJECTS: Twenty domestic pigs of either gender. INTERVENTIONS: After induction
      of fecal peritonitis, anesthetized and instrumented pigs were ventilated with
      either 100% oxygen or supplemental oxygen as needed to maintain arterial
      hemoglobin oxygen saturation > or = 90%. Normotensive and hyperdynamic
      hemodynamics were achieved using hydroxyethyl starch and norepinephrine infusion.
      MEASUREMENTS AND MAIN RESULTS: Before and at 12, 18, and 24 hrs of peritonitis,
      we measured lung compliance; systemic, pulmonary, and hepatosplanchnic
      hemodynamics; gas exchange; acid-base status; blood isoprostanes; nitrates; DNA
      strand breaks; and organ function. Gluconeogenesis and glucose oxidation were
      calculated from blood isotope and expiratory 13CO2 enrichments during continuous
      intravenous 1,2,3,4,5,6-(13)C6-glucose. Apoptosis in lung and liver was assessed
      postmortem (TUNEL staining). Hyperoxia did not affect lung mechanics or gas
      exchange but redistributed cardiac output to the hepatosplanchnic region,
      attenuated regional venous metabolic acidosis, increased glucose oxidation,
      improved renal function, and markedly reduced the apoptotic death rate in liver
      and lung. CONCLUSIONS: During early hyperdynamic porcine septic shock, 100%
      oxygen improved organ function and attenuated tissue apoptosis without affecting
      lung function and oxidative or nitrosative stress. Therefore, it might be
      considered as an additional measure in the first phase of early goal-directed
      therapy.

PMID- 18091554
TI  - Impact of a clinical pharmacist-enforced intensive care unit sedation protocol on
      duration of mechanical ventilation and hospital stay.
AB  - OBJECTIVE: While the use of a protocol to guide sedation and analgesia therapy in
      the intensive care unit has been shown to improve patient outcomes, compliance is
      often poor. We hypothesized that a formal, consistent intervention by pharmacists
      to promote adherence to our institution's sedation guidelines would improve
      clinical outcomes. The purpose of this study was to document the impact of daily
      pharmacist interventions on clinical outcomes of intensive care unit patients
      prescribed continuous sedative therapy. DESIGN: Before-after study. SETTING: Two
      medical intensive care units (total of 18 beds) at a university medical center.
      PATIENTS: Patients were 156 mechanically ventilated patients prescribed a
      continuous infusion of sedative medication while in the medical intensive care
      unit. INTERVENTIONS: In the retrospective group, data were collected on all
      mechanically ventilated patients receiving continuous sedative infusions over a 3
      month period. In the prospective group, a pharmacist evaluated all mechanically
      ventilated patients on continuous sedation daily and made recommendations to
      adhere to the institution's previously approved sedation guidelines. MEASUREMENTS
      AND MAIN RESULTS: Data were collected for 78 control and 78 intervention
      patients. The groups were well matched in terms of baseline demographics. The
      mean duration of mechanical ventilation was reduced from 338 +/- 348 hrs (14
      days) in the pre-intervention group to 178 +/- 178 hrs (7.4 days) in the
      postintervention group (p < .001). Durations of both intensive care unit stay
      (380 +/- 325 hrs vs. 238 +/- 206 hrs, p = .001) and hospital stay (537 +/- 350
      hrs vs. 369 +/- 274 hrs, p = .001) were also significantly reduced in the post
      intervention group. CONCLUSIONS: The institution of a daily pharmacist-enforced
      intervention directed at improving sedation guideline adherence resulted in a
      significant decrease in the duration of mechanical ventilation in patients
      receiving continuous sedation.

PMID- 18091555
TI  - Anatomical and functional intrapulmonary shunt in acute respiratory distress
      syndrome.
AB  - OBJECTIVES: The lung-protective strategy employs positive end-expiratory pressure
      to keep open otherwise collapsed lung regions (anatomical recruitment).
      Improvement in venous admixture with positive end-expiratory pressure indicates
      functional recruitment to better gas exchange, which is not necessarily related
      to anatomical recruitment, because of possible global/regional perfusion
      modifications. Therefore, we aimed to assess the value of venous admixture
      (functional shunt) in estimating the fraction of nonaerated lung tissue
      (anatomical shunt compartment) and to describe their relationship. DESIGN:
      Retrospective analysis of a previously published study. SETTING: Intensive care
      units of four university hospitals. PATIENTS: Fifty-nine patients with acute lung
      injury/acute respiratory distress syndrome. INTERVENTIONS: Positive end
      expiratory pressure trial at 5 and 15 cm H2O positive end-expiratory pressures.
      MEASUREMENTS AND MAIN RESULTS: Anatomical shunt compartment (whole-lung computed
      tomography scan) and functional shunt (blood gas analysis) were assessed at 5 and
      15 cm H2O positive end-expiratory pressures. Apparent perfusion ratio (perfusion
      per gram of nonaerated tissue/perfusion per gram of total lung tissue) was
      defined as the ratio of functional shunt to anatomical shunt compartment.
      Functional shunt was poorly correlated to the anatomical shunt compartment (r2 =
      .174). The apparent perfusion ratio at 5 cm H2O positive end-expiratory pressure
      was widely distributed and averaged 1.25 +/- 0.80. The apparent perfusion ratios
      at 5 and 15 cm H2O positive end-expiratory pressures were highly correlated, with
      a slope close to identity (y = 1.10.x -0.03, r2 = .759), suggesting unchanged
      blood flow distribution toward the nonaerated lung tissue, when increasing
      positive end-expiratory pressure. CONCLUSIONS: Functional shunt poorly estimates
      the anatomical shunt compartment, due to the large variability in apparent
      perfusion ratio. Changes in anatomical shunt compartment with increasing positive
      end-expiratory pressure, in each individual patient, may be estimated from
      changes in functional shunt, only if the anatomical-functional shunt relationship
      at 5 cm H2O positive end-expiratory pressure is known.

PMID- 18091557
TI  - Failure of neuronal maturation in Alzheimer disease dentate gyrus.
AB  - The dentate gyrus, an important anatomic structure of the hippocampal formation,
      is one of the major areas in which neurogenesis takes place in the adult
      mammalian brain. Neurogenesis in the dentate gyrus is thought to play an
      important role in hippocampus-dependent learning and memory. Neurogenesis has
      been reported to be increased in the dentate gyrus of patients with Alzheimer
      disease, but it is not known whether the newly generated neurons differentiate
      into mature neurons. In this study, the expression of the mature neuronal marker
      high molecular weight microtubule-associated protein (MAP) isoforms MAP2a and b
      was found to be dramatically decreased in Alzheimer disease dentate gyrus, as
      determined by immunohistochemistry and in situ hybridization. The total MAP2,
      including expression of the immature neuronal marker, the MAP2c isoform, was less
      affected. These findings suggest that newly generated neurons in Alzheimer
      disease dentate gyrus do not become mature neurons, although neuroproliferation
      is increased.

PMID- 18091558
TI  - TAR-DNA binding protein 43 in Pick disease.
AB  - Pick disease (PiD) is a frontotemporal dementia characterized by frontal and
      temporal atrophy, neuronal loss, gliosis, ballooned neurons that are positive for
      alpha-B crystallin and neurofilament, and the presence of tau- and ubiquitin
      positive Pick bodies. TAR-DNA binding protein 43 (TDP-43) has been found to be a
      component of ubiquitinated inclusions in other neurodegenerative diseases,
      including frontotemporal lobar degeneration with ubiquitinated inclusions and
      amyotrophic lateral sclerosis. Fifteen cases of PiD were examined using
      immunohistochemical methods, and 5 cases with both Pick bodies and smaller
      intracytoplasmic inclusions that showed staining for ubiquitin, tau, and TDP-43
      were observed. The presence of TDP-43 inclusions in PiD suggests that TDP-43
      accumulation may be an important component of many neurodegenerative diseases,
      and that its presence in only some cases of PiD may indicate different pathways
      of disease development.

PMID- 18091559
TI  - Molecular diagnostic testing in malignant gliomas: a practical update on
      predictive markers.
AB  - Advances in understanding the molecular underpinnings of cancer and in molecular
      diagnostic technologies have changed the clinical practice of oncologic
      pathology. The development of targeted therapies against specific molecular
      alterations in cancer further portends changes in the role of the pathology
      laboratory to guide such custom therapies. To reconcile the flood of scientific
      discoveries in this area, the promises of highly touted novel therapeutics, and
      the practicality of applying this knowledge to the day-to-day practice of
      clinical neuropathology, the present review highlights the operative differences
      between diagnostic, predictive, and prognostic markers, and discusses issues
      surrounding the transition of prospective biomarkers to routine laboratory
      implementation. This review focuses on 3 predictive molecular markers that are
      either in clinical use or are contemplated for use in the evaluation of malignant
      gliomas: assessment of 1p/19q loss in oligodendroglial tumors, examination of O6
      methylguanine DNA methyltransferase promoter methylation status in glioblastomas,
      and molecular dissection of the epidermal growth factor receptor
      phosphatidylinositol 3-kinase pathway in glioblastomas. Implementation of such
      predictive markers is not straightforward and requires critical review of the
      available literature and attention to practical laboratory, compliance,
      financial, and clinical management issues.

PMID- 18091560
TI  - Fetal blood-brain barrier P-glycoprotein contributes to brain protection during
      human development.
AB  - During brain development and blood-brain barrier (BBB) differentiation the
      expression of P-glycoprotein (P-gp) may complement the protective function of the
      placental barrier against xenobiotic substances. To establish an
      immunohistochemical procedure for P-gp detection, different anti-P-gp monoclonal
      antibodies were first tested on a fibrosarcoma cell line and colonic carcinoma
      tissue. The protocol was then tested on adult human brains as a BBB-P-gp tissue
      specific control and for double labeling with anti-P-gp and the astroglia marker
      glial fibrillary acidic protein (GFAP). The protocol was then used to analyze the
      expression and localization of P-gp in human fetuses during cerebral cortex
      formation. At the earliest examined stage, 12 weeks of gestation (wg), P-gp was
      detectable as diffuse cytoplasmic labeling of the endothelial cells lining the
      primary cortex microvessels. At 18 wg, a punctate P-gp staining pattern was
      detected on cortex and subcortical vessels and on their side branches. At 22 wg,
      P-gp staining was linear and concentrated on endothelial cell membranes. In all
      examined ages, GFAP-positive radial glial cells and astrocytes did not stain for
      P-gp, even at their perivascular processes, whereas faint P-gp labeling was seen
      on vimentin-reactive radial glia at the earliest examined fetal age. At
      midgestation, P-gp colocalized with caveolin-pY14 on the abluminal endothelial
      cell membrane. These results demonstrate that P-gp is expressed early during
      human cerebral cortical microvessel development, and suggest that at midgestation
      there may be efflux activity that is regulated by interactions with the caveolar
      endothelial cell compartment.

PMID- 18091561
TI  - Limited clearance of pre-existing amyloid plaques after intracerebral injection
      of Abeta antibodies in two mouse models of Alzheimer disease.
AB  - Recent studies have demonstrated the potential utility of antibodies for the
      treatment of Alzheimer disease (AD). In transgenic mouse models of AD, peripheral
      and intracerebral administration of Abeta-specific antibodies reduces amyloid
      burdens to varied extents. The mechanism may involve clearance of pre-existing
      amyloid plaques or prevention of new amyloid formation. Here, we have used two
      transgenic models, the inducible CamKII-ttAxtetAPP/swe/ind (Line 107) and the
      APPswe/PS1dE9 (Line 85), to test the ability of intracerebral injection of Abeta
      antibodies to clear amyloid. Because the production of Abeta peptides in the Line
      107 model is inducible, whereas production in Line 85 mice is constitutive, we
      could study the effects of antibody on pre-existing plaques versus continuous
      plaque formation. In Line 85, injection of antibody resulted in modest but
      statistically significant reductions in amyloid burden (average, 14%-16%).
      However, injected antibodies had no effect on amyloid burden in Line 107 under
      conditions in which the production of Abeta was suppressed, indicating that pre
      existing plaques are not rapidly cleared. These results indicate that
      intracerebral injection of Abeta antibodies produces modest reductions in amyloid
      deposition in these two models and that the mechanism may involve prevention of
      amyloid formation rather than clearance of pre-existing plaques.

PMID- 18091562
TI  - Inclusion body myositis associated with human T-lymphotropic virus-type I
      infection: eleven patients from an endemic area in Japan.
AB  - The objective of this study was to investigate the association of human T
      lymphotropic virus-type I (HTLV-I) infection with sporadic inclusion body
      myositis in 11 patients from an endemic area in Japan. The clinical features were
      consistent with sporadic inclusion body myositis, and anti-HTLV-I antibodies were
      present in the sera of all patients. Their muscle biopsies showed the diagnostic
      features of inclusion body myositis, including endomysial T-cell infiltration,
      rimmed vacuoles, deposits of phosphorylated tau, and abnormal filaments in the
      nuclei and cytoplasm of the myofibers. The fibers expressed major
      histocompatibility complex class I antigens and were invaded by CD8 and CD4
      cells. In a single human leukocyte antigen-A2-positive patient, in situ human
      leukocyte antigen-A*0201 / Tax11-19-pentamer staining showed pentamer-positive
      cells surrounding the muscle fibers. Double-immunogold silver staining and
      polymerase chain reaction in situ hybridization revealed that HTLV-I proviral DNA
      was localized on helper-inducer T cells, but not on muscle fibers. Human T
      lymphotropic virus-type I proviral loads in peripheral blood mononuclear cells
      from each patient were similar to those in HTLV-I-associated myelopathy/tropical
      spastic paraparesis. This study suggests that HTLV-I infection may be one of the
      causes of sporadic inclusion body myositis, as has been reported in human
      immunodeficiency virus type-1 infection.

PMID- 18091563
TI  - Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a
      model of human congenital neuronal ceroid-lipofuscinosis.
AB  - Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency
      of which causes early-onset and particularly aggressive forms of neuronal ceroid
      lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are
      characterized by severe neurodegeneration, but the molecular mechanisms behind
      the neuronal death remain poorly understood. In this study, we have
      systematically mapped the distribution of neuropathologic changes in CTSD
      deficient mouse brains by stereologic, immunologic, and electron microscopic
      methods. We report highly accentuated neuropathologic changes within the ventral
      posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of
      thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF),
      which receive and send information to the thalamic VPM/VPL. These changes
      included pronounced astrocytosis and microglial activation that begin in the
      VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced
      neuronal number and redistribution of presynaptic markers. In addition, loss of
      synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin
      were observed in the VPM/VPL. These synaptic alterations are accompanied by
      changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates
      formation of the SNARE complex at the synapse. Taken together, these data reveal
      the somatosensory thalamocortical circuitry as a particular focus of pathologic
      changes and provide the first evidence for synaptic alterations at the molecular
      and ultrastructural levels in CTSD deficiency.

PMID- 18091564
TI  - Type-specific HPV infection and multiple HPV types: prevalence and risk factor
      profile in nearly 12,000 younger and older Danish women.
AB  - OBJECTIVES: Human papillomavirus (HPV) is considered a necessary cause of
      cervical cancer. The aim of the current study was to determine the burden of HPV
      infection among randomly sampled Danish women before the vaccine against HPV is
      implemented. Further we assessed the risk factor profile for prevalent high risk
      (HR) HPV infection and infection with multiple HR HPV types. METHODS: In the
      present cross-sectional study, we used baseline data from a population-based
      cohort study where participants were interviewed and had a gynecological
      examination. Cervical samples were analyzed for HR HPV using Hybrid capture 2 in
      10,544 women aged 20-29 years and 1443 women aged 40-50 years. Genotyping was
      performed using LiPA. RESULTS: The prevalence of HR HPV was 17.9% and 4.4% in
      women aged 20-29 years and 40-50 years, respectively. HPV16 was the most common
      HR type overall and among women with abnormal cytology. Multiple HPV types were
      highly prevalent, notably in the younger cohort. Lifetime number of sexual
      partners was the main risk factor for HR HPV infection (adj. OR = 2.8 and OR =
      3.4 for > or =15 partners vs. < or =4 in respectively younger and older women),
      whereas number of recent sexual partners was only associated with risk in younger
      women. Number of partners, oral contraceptive use and self-reported chlamydia
      infection increased the risk of having multiple HR HPV types (compared to having
      a single HR HPV type). CONCLUSIONS: HR HPV infection was common among younger
      women, with HPV16 as the predominant type. We confirmed the importance of sexual
      activity for the risk of HR HPV infection. In addition, we found that sexual
      behavior also play an important role for the risk of having multiple HR HPV
      types.

PMID- 18091565
TI  - Lymphogranuloma venereum proctitis in men who have sex with men is associated
      with anal enema use and high-risk behavior.
AB  - OBJECTIVES: In the industrialized world, lymphogranuloma venereum proctitis
      (LGVP) has been reported only in men who have sex with men. Factors responsible
      for the outbreak remain to be elucidated. GOAL: The goal of the present work was
      to elucidate risk factors associated with LGVP. STUDY DESIGN: The study design
      comprised a cross-sectional study including 32 men with LGVP and 93 men without
      LGVP (22 with gonorrheal proctitis, 30 with a non-LGV chlamydial proctitis, and
      41 with proctitis of unknown etiology). Factors associated with LGVP were
      analyzed by (multinomial) logistic regression. RESULTS: Comparing men with LGVP
      with men without LGVP, factors significantly associated with higher risk of LGVP
      in multivariate analyses were as follows: anal enema use [odds ratio (OR): 7.8,
      95% confidence interval (CI): 2.6-23.2], having sex on sex parties (OR: 5.7, 95%
      CI: 1.5-21.8), and having sex with human immunodeficiency virus-positive partners
      (OR: 3.2, 95% CI: 1.1-9.3). Evaluating the 4 proctitis groups separately in a
      multinomial logistic regression model, similar associations between anal enema
      use and LGVP were found. Men with non-LGV chlamydial proctitis showed less risk
      behavior than men with LGVP. No substantial difference in risk behavior was
      found, except for attending sex parties, between men with LGVP, and gonorrheal
      proctitis or proctitis of unknown etiology. CONCLUSIONS: Apart from men with
      LGVP, men with gonorrheal proctitis or proctitis of unknown etiology exhibit high
      risk behavior. Enema use seems to play a key role in transmission of LGVP, and
      needs further investigation.

PMID- 18091567
TI  - Endotoxin causes pulmonary hypertension by upregulating smooth muscle endothelin
      type-B receptors: role of aldose reductase.
AB  - Endothelin-1 (ET-1), a potent vasoconstrictor and mitogen, is upregulated in
      pulmonary tissue during endotoxemia and contributes markedly to endotoxin-induced
      pulmonary hypertension. It is, however, unknown whether the ET receptors, ET(A)
      and ET(B), are differentially regulated in endotoxemic pulmonary vasculature and
      how this may impact on pulmonary vascular tone. To investigate this topic, we
      used isolated perfused lungs, pulmonary endothelial cells (ECs), and pulmonary
      vascular smooth muscle cells (SMCs) of the rat. During a 6-h endotoxin exposure,
      isolated perfused lungs developed significant pulmonary hypertension that was
      markedly attenuated by antagonizing ET(A) or ET(B) receptors using subtype
      selective or a mixed ET(A/B) receptor antagonist. Peptide levels of big ET-1 and
      ET-1 and gene expression of prepro-ET-1 were increased after endotoxin challenge
      in all tissues. In endotoxemic isolated perfused lungs and ECs, the significant
      rise of mature ET-1 seen in controls after ET(B) receptor or mixed antagonism
      disappeared completely. However, this effect was preserved in endotoxemic SMCs.
      In ECs, endotoxin markedly downregulated maximum ET(B) receptor sites and ET(B)
      mRNA levels, whereas in SMCs, it generated substantial ET(B) receptor
      upregulation and moderate ET(A) receptor downregulation. The aldose reductase
      inhibitors sorbinil and zopolrestat mitigated endotoxin-induced pulmonary
      hypertension, ET-1 stimulation, and differential ET(B) receptor regulation. We
      conclude that endotoxin-induced pulmonary hypertension in the rat results from a
      loss of endothelial and concomitant gain of vascular smooth muscle ET(B)
      receptors. These changes are at least partly mediated by aldose reductase.

PMID- 18091568
TI  - Role of host defense peptides of the innate immune response in sepsis.
AB  - Innate immune response and its effector molecules have received growing attention
      in research. Host defense peptides are known to be antimicrobially active.
      Recently, the peptides have been recognized as potent signaling molecules for
      cellular effectors of both innate and adaptive immunity. Mammalian peptides in
      particular revealed immunomodulatory functions, including endotoxin-binding and 
      neutralizing capacity, chemotactic activities, induction of cytokines and
      chemokines, promotion of wound healing, and angiogenesis. In sepsis, they present
      a family of natural substances that can be used in combination with antibiotics
      to complete a broad-spectrum antimicrobial regimen with endotoxin-neutralizing
      properties. Although there are side effects, host defense peptides have the
      potential to be significant reinforcements to the currently available therapeutic
      options in the future. In this review, we analyze the role of host defense
      peptides in infection and immune response, and discuss recent efforts to
      establish host defense peptides as potent novel therapeutic agents for the
      treatment of sepsis.

PMID- 18091569
TI  - Effect of sesame oil against acetaminophen-induced acute oxidative hepatic damage
      in rats.
AB  - Acetaminophen (APAP) overdose causes acute liver injury or even death in both
      humans and experimental animals. We investigated the effect of sesame oil on APAP
      induced acute liver injury. Male Wistar rats were given APAP (1,000 mg/kg;
      orally) to induce acute liver injury. Acetaminophen significantly increased
      aspartate transaminase, alanine transaminase, lipid peroxidation, and superoxide
      anion and hydroxyl radical generation levels; it also induced glutathione
      depletion. Sesame oil (8 mL/kg; orally) did not alter the gastric absorption of
      APAP, but it inhibited all the parameters altered by APAP and protected the rats
      against APAP-induced acute liver injury. We hypothesize that sesame oil
      maintained the intracellular glutathione levels, reduced reactive oxygen species
      levels, and inhibited lipid peroxidation in rats with APAP-induced acute liver
      injury.

PMID- 18091571
TI  - Adenosine triphosphate-sensitive potassium channels prevent extension of
      myocardial ischemia to subepicardium during hemorrhagic shock.
AB  - Cardiac dysfunction during hemorrhagic shock (HS) is associated with myocardial
      ischemia, during which adenosine triphosphate (ATP)-sensitive potassium (K(ATP))
      channels can be activated. We investigated the role of K(ATP) channels in HS
      induced myocardial ischemia. Canine HS was induced using an aortic reservoir to
      maintain the aortic pressure at a constant 40 mmHg. To visualize the myocardial
      ischemia as a nicotinamide adenine dinucleotide (NADH) - fluorescent area, the
      beating hearts were rapidly cross-sectioned (120 ms) and freeze-clamped (-190
      degrees C) using a sampling device after 10 min of HS. The effect of a K(ATP)
      channel blocker, glibenclamide (1 mg/kg, i.v.), on myocardial ischemia was also
      quantified. Regional myocardial blood flow was measured using heavy element
      loaded nonradioactive microspheres. Myocardial ischemia developed in the
      subendocardium in the HS alone group, whereas it extended through all the cardiac
      layers in the glibenclamide-treatment group. The coadministration of a K(ATP)
      channel opener, cromakalim (50 microg/kg, i.v.), with glibenclamide prevented the
      extension of myocardial ischemia to the subepicardium. Glibenclamide decreased
      the myocardial ATP concentration selectively in the subepicardium during HS. The
      HS decreased myocardial blood flow transmurally, and following the administration
      of glibenclamide, further decreased the blood flow selectively in the
      subepicardium. These results suggest that K(ATP) channels are activated during
      HS, enabling selective subepicardial coronary dilatation and protecting the
      myocardium from the extension of myocardial ischemia to the subepicardium.

PMID- 18091570
TI  - A3 and P2Y2 receptors control the recruitment of neutrophils to the lungs in a
      mouse model of sepsis.
AB  - We have recently shown that A3 adenosine receptors and P2Y2 purinergic receptors
      play an important role in neutrophil chemotaxis. Chemotaxis of neutrophils to
      sites of infections is critical for immune defense. However, excessive
      accumulation of neutrophils in the lungs can cause acute lung tissue damage. Here
      we assessed the role of A3 and P2Y2 receptors in neutrophil sequestration to the
      lungs in a mouse model of sepsis. Sepsis was induced by cecal ligation and
      puncture (CLP) using adult male C57BL/6J mice (wild type [WT]), homozygous A3
      receptor knockout (A3KO) mice, and P2Y2 receptor knockout (P2Y2KO) mice. Animals
      were killed 2, 4, 6, or 8 h after CLP, and peritoneal lavage fluid and blood were
      collected. Lungs were removed, and neutrophil infiltration was evaluated using
      elastase as a marker. Leukocyte and bacterial counts in peritoneal lavage fluid
      and blood samples were determined. Survival after sepsis was determined in a
      separate group. Leukocyte counts in the peritoneum were lower in A3KO and P2Y2KO
      mice than in WT mice. Conversely, initial leukocyte counts in the peripheral
      blood were higher in KO mice than in WT mice. Neutrophil sequestration to the
      lungs reached a maximum 2 h after CLP and remained significantly higher in WT
      mice compared with A3KO and P2Y2KO mice (P < 0.001). Survival after 24 h was
      significantly lower in WT mice (37.5%) than in A3KO or P2Y2KO mice (82.5%; P <
      0.05). These data suggest that A3 and P2Y2 receptors are involved in the influx
      of neutrophils into the lungs after sepsis. Thus, pharmaceutical approaches that
      target these receptors might be useful to control acute lung tissue injury in
      sepsis.

PMID- 18091572
TI  - Effects of intrarenal administration of the calcium antagonist nimodipine during
      porcine aortic occlusion-induced ischemia/reperfusion injury.
AB  - Ca++ antagonists have been tested to improve I/R injury in the kidney, but their
      clinical use is limited due to their hypotensive properties. Therefore, we tested
      the hypothesis on whether infusing the Ca++ blocker nimodipine directly into the
      renal artery would reduce kidney cell apoptosis and thus improve organ function
      in a porcine model of suprarenal abdominal aortic cross-clamping. In a
      prospective, randomized, controlled, blinded study, anesthetized, mechanically
      ventilated, and instrumented pigs underwent 45 min of suprarenal aortic cross
      clamping animals receiving either 0.25 microg kg(-1) min(-1) nimodipine (n = 8)
      or vehicle (n = 8). Systemic and right kidney hemodynamics, oxygen exchange, and
      metabolism were assessed before clamping, as well as before and at 75 and 195 min
      of reperfusion (i.e., at 120 and 240 min after aortic occlusion). At the end of
      the experiments, the right kidney was harvested for conventional hematoxylineosin
      staining and immunohistochemistry for the cyclin-dependent kinase inhibitor
      p21(WAF1/CIP1) gene expression and apoptosis (terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate-biotin end labeling test). Neither
      systemic nor renal hemodynamics and oxygen exchange, plasma and urine protein
      concentrations, urine osmolarity, and lactate-pyruvate ratios showed any
      intergroup difference. Nimodipine infusion resulted in a significantly higher
      creatinine clearance after 195 min of reperfusion (26 [17 - 42] vs. 17 [9 - 22]
      mL x min(-1)) and attenuated renal tubular damage, as indicated by lower urinary
      small protein (25 kd) concentrations. Improved renal function was concomitant
      with significantly less pronounced positive nuclear terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate-biotin end labeling staining. In a
      porcine model of suprarenal aortic cross-clamping, intrarenal nimodipine infusion
      improved postischemia kidney function, most likely as a result of attenuated
      glomerular apoptosis.

PMID- 18091573
TI  - Circulating angiopoietin 2 correlates with mortality in a surgical population
      with acute lung injury/adult respiratory distress syndrome.
AB  - There are few blood biomarkers predictive of mortality in adult respiratory
      distress syndrome (ARDS), and none that currently serve as therapeutic targets.
      Here, we ask whether a circulating protein angiopoietin 2 (Ang2) correlates with
      severity of lung injury and mortality in a surgical intensive care unit cohort
      with acute lung injury (ALI)/ARDS. Tie 2 is a tyrosine kinase receptor expressed
      on endothelial cells. One ligand, angiopoietin 1, phosphorylates Tie 2 and
      stabilizes adult vasculature. An alternate ligand, Ang2, serves as a context
      dependent antagonist and disrupts barrier function. Previously, our laboratory
      detected high circulating Ang2 levels in septic patients and a correlation with
      low Pa(O2)/F(IO2). In this study, daily plasma was collected in 63 surgical
      intensive care unit patients. Eighteen patients met clinical criteria for ALI or
      ARDS. The median Ang2 at admission in patients who never developed ALI/ARDS was
      3.7 ng/mL (interquartile range [IQR], 5.6; n = 45). The Ang2 on the day a patient
      met criteria for ALI/ARDS was 5.3 ng/mL (IQR, 6.7) for survivors (n = 11) and
      19.8 ng/mL (IQR, 19.2) for nonsurvivors (n = 7; P= 0.004). To explore the
      mechanism of high Ang 2 leading to increased permeability, plasma from patients
      with ALI was applied to cultured lung endothelial cells and found to disrupt
      normal junctional architecture. This effect can be rescued with the Tie 2 agonist
      angiopoietin 1. A patient's convalescent (low Ang2) plasma did not disrupt
      junctional architecture. Although further studies with larger sample sizes will
      be needed to confirm these results, high Ang2 in critically ill patients with
      ALI/ARDS is associated with a poor outcome. These data, coupled with our cell
      culture experiments, suggest that antagonism of Ang2 may provide a future novel
      therapeutic target for ARDS.

PMID- 18091574
TI  - Low-dose candesartan improves renal blood flow and kidney oxygen tension in rats
      with endotoxin-induced acute kidney dysfunction.
AB  - Sepsis is associated with an activation of the renin-angiotensin system and
      causes acute kidney injury. The aim was to examine the effects of a low,
      nondepressor dose of the selective angiotensin II type 1 receptor antagonist
      candesartan on renal hemodynamics and function in endotoxemic rats. Endotoxemia
      was induced in Sprague-Dawley rats by a dose of LPS (Escherichia coli O127:B8;
      7.5 mg kg(-1), i.p.). At 16 h after endotoxin administration, renal clearance
      experiments were performed in thiobutabarbital anesthetized rats. Study groups
      (1) sham-saline, (2) LPS-saline, and (3) LPS-candesartan received isotonic saline
      or candesartan (10 microg kg(-1), i.v.) after baseline measurements. Kidney
      function, renal blood flow (RBF), and cortical and outer medullary perfusion
      (laser-Doppler flowmetry) and oxygen tension (P(O2); Clark-type microelectrodes)
      were analyzed during 2 h after drug administration. At baseline, endotoxemic rats
      showed an approximately 50% reduction in glomerular filtration rate and RBF (P <
      0.05), a decline in cortical and outer medullary perfusion, and Po2 (P < 0.05),
      but no significant alterations in MAP compared with saline-injected controls.
      Candesartan treatment significantly improved RBF (+40% +/- 6% vs. baseline),
      cortical perfusion (+18% +/- 3% vs. baseline), and cortical (+19% +/- 7% vs.
      baseline) and outer medullary (+22% +/- 10% vs. baseline) P(O2) in endotoxemic
      rats (P < 0.05 vs. LPS-saline). Candesartan did not significantly influence MAP
      or glomerular filtration rate, whereas filtration fraction was reduced by 27% +/-
      5% vs. baseline (P < 0.05 vs. LPS-saline). In conclusion, candesartan, in a dose
      that did not significantly decrease MAP, caused renal vasodilation and markedly
      improved RBF and intrarenal P(O2) in endotoxemic rats. These findings suggest
      renoprotective effects of candesartan in sepsis.

PMID- 18091575
TI  - Roles of epoxyeicosatrienoic acids in vascular regulation and cardiac
      preconditioning.
AB  - Continuing investigations of the roles of cytochrome P450 (CYP) arachidonic acid
      epoxygenase metabolites in the regulation of cardiovascular physiology and
      pathophysiology have revealed their complex and diverse biological effects. Often
      these metabolites demonstrate protective properties that are revealed during
      cardiovascular disease. In this regard, the epoxyeicosatrienoic acids (EETs) are
      an emerging target for pharmacological manipulation aimed at enhancing their
      cardiac and vascular protective mechanisms. This review will focus on the role of
      EETs in the regulation of vascular tone, with emphasis on the coronary
      circulation, their role in limiting platelet aggregation, vascular inflammation
      and EET contribution to preconditioning of the ischemic myocardium. Production
      and metabolism of EETs as well as their specific cellular signaling mechanisms
      are discussed.

PMID- 18091576
TI  - Arachidonic Acid metabolites in the cardiovascular system: the role of
      lipoxygenase isoforms in atherogenesis with particular emphasis on vascular
      remodeling.
AB  - Vascular remodeling refers to lasting structural alterations in the vessel wall
      that are initiated in response to external and internal stimuli. These changes
      are distinct from acute functional responses of blood vessels when challenged by
      increased blood pressure, altered hemodynamics, or vasoactive mediators. In early
      atherogenesis, when lesion formation is starting to impact local hemodynamics,
      the vessel wall responds with outward vascular remodeling to maintain normal
      blood flow. However, inward remodeling may also occur during the time course of
      plaque formation, contributing to vascular stenosis. Lipoxygenases form a
      heterogeneous family of lipid-peroxidizing enzymes, which have been implicated in
      atherogenesis. Several lines of in vitro and in vivo evidence indicated their
      involvement in disease development, but the precise function of different
      lipoxygenase isoforms is still a matter of discussion. Vascular remodeling is an
      early response during plaque development; therefore, lipoxygenases may be
      involved in this process. Unfortunately, little is known about the potential role
      of lipoxygenase isoforms in vascular remodeling. This review will briefly
      summarize our knowledge of the role of lipoxygenases in vascular biology and will
      critically review the activities of the 3 most athero-relevant lipoxygenase
      isoforms in atherogenesis, with particular emphasis on vascular remodeling.

PMID- 18091577
TI  - Mechanisms of ET-1-induced endothelial dysfunction.
AB  - There is now increasing evidence that endothelial dysfunction is an early event
      in the pathophysiology of cardiovascular diseases and can be corrected with
      certain therapies such as angiotensin converting enzyme inhibitors angiotensin
      type I receptor antagonists and stains independently of blood pressure lowering
      effects. Restoring endothelial function appears to be a crucial target since
      endothelial dysfunction predicts cardiovascular events in various situations such
      as coronary artery disease peripheral artery disease, or hypertension and in
      patients undergoing vascular surgery. Preclinical and clinical data strongly
      support that endothelin receptor antagonists belong to this restricted class of
      pharmacological agents able to act on the endothelium, and offer a potential
      therapeutic approach for numerous diseases associated with endothelial
      dysfunction. The purpose of this review will be therefore, 1) to propose
      mechanisms by which ET-1 can cause endothelial dysfunction; 2) to provide an
      overview of pathological situations associated with endothelial dysfunction
      related to ET-1; and 3) to assemble evidence on efficacy of endothelin receptor
      antagonists for improvement of endothelial function.

PMID- 18091578
TI  - The impact of acute myocardial ischemia on the ventricular defibrillation
      threshold during chronic oral azimilide therapy.
AB  - The effects of chronic oral azimilide therapy on the ventricular defibrillation
      threshold (DFT) during ischemia are unknown. The effects of azimilide on
      defibrillation efficacy under ischemic condition were investigated in a closed
      chest animal model. Azimilide (20 mg/kg/d) was administered orally for 7 days to
      10 pigs (20 to 25 kg). The control group (no treatment) comprised 15 pigs. A 2
      lead defibrillation system was used. Each shock was delivered after 8 seconds of
      ventricular fibrillation. A step-up and step-down protocol was used to calculate
      mean DFT before and 10 minutes after coronary artery occlusion using an
      angioplasty balloon in the left descending artery. The basal DFT of the azimilide
      group did not differ from controls (20.8 +/- 4.8 versus 18.8 +/- 2.8; P = 0.33).
      After ischemia, the mean DFT of the azimilide-treated animals was similar to
      controls (21.8 +/- 5.2 versus 23.2 +/- 3.8 J; P = 0.54), despite significant
      lengthening of ventricular repolarisation (428.2 +/- 51.8 versus 494.1 +/- 46.6
      msec; P = 0.005) and significant prolongation of the ventricular fibrillation
      cycle length (85.1 +/- 13 versus 104.7 +/- 24 msec; P < 0.04). Chronic oral
      azimilide treatment does not affect the DFT at baseline or during acute
      myocardial ischemia.

PMID- 18091579
TI  - A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits
      neointima formation after angioplasty in an obese diabetic rodent model.
AB  - We investigated whether targeted cleavage of PAI-1 mRNA might prevent post
      angioplasty neointima formation in diabetic JCR:LA-cp/cp rats with naturally
      elevated PAI-1 levels. Catalytic DNA enzymes targeting rat PAI-1 mRNA (PAI-1 DNA
      enzyme, n = 12) or a random sequence as control (scrambled DNA enzyme, n = 12)
      were infused at the site of arterial damage. Control animals demonstrated
      prominent PAI-1 protein expression in the arterial endothelium at 48 hours, and
      robust neointimal proliferation by two weeks, with 60 +/- 10% mean occlusion of
      the artery lumen. The neointimal lesion consisted of dense fibrin deposition and
      numerous proliferating smooth muscle cells, as determined by dual alpha-smooth
      muscle actin/Ki67 expression. Treatment with PAI-1 DNA enzyme resulted in marked
      early (48 hour) reduction of endothelial PAI-1 protein expression, which
      persisted for the next two weeks as well as a two fold reduction of expression of
      PAI-1 mRNA by RT-PCR at the same time point, (P < 0.05). By two weeks, PAI-1 DNA
      enzyme treated animals demonstrated significantly reduced levels of fibrin
      deposition and 5-fold lower levels of proliferating smooth muscle cells at the
      site of arterial injury compared to controls (P < 0.01), and a 2-fold lower
      neointima/media ratio (0.67 +/- 0.11 vs 1.39 +/- 0.12) (P < 0.05). Treatment with
      a catalytic PAI-1 DNA enzyme successfully prevents neointimal proliferation after
      balloon injury in diabetic animals.

PMID- 18091580
TI  - Role of nitric oxide and prostaglandin systems in lithium modulation of
      acetylcholine vasodilation.
AB  - The mechanism of lithium action, an effective treatment for bipolar disease, is
      still unknown. The present study examined the role of nitric oxide (NO) and
      prostaglandin systems in lithium modulation of acetylcholine in mesenteric
      vascular bed of rats by cannulating superior mesenteric artery. Acetylcholine
      (ACh) or sodium nitroprusside was injected under constant controlled flow induced
      by phenylephrine; therefore, changes in perfusion pressure reflect changes in
      resistance. Although 0.5 mM or 1 mM lithium-pretreatment of vascular bed causes
      reduction in ACh-response, 1.5 mM lithium induced no changes and 2 and 2.5 mM
      lithium potentiated ACh-induced mesenteric vascular bed relaxation compared to
      control group. Pretreatment of vascular bed with L-NAME or indomethacin decreased
      ACh-induced relaxation in 2 concentrations of 0.5 and 2 mM of lithium. The
      vasorelaxation response to sodium nitroprusside, the NO donor, was not different
      among lithium groups (0.5 and 2 mM) and controls. In conclusion, there is a dual
      modulation of endothelium-dependent relaxation, including an inhibitory effect at
      lower dose and a stimulating effect at higher dose of lithium in rat mesenteric
      vascular bed. NO synthesis or cyclooxygenase inhibition decreased vasorelaxation
      in both lower and higher doses of lithium, suggesting a role for NO and
      prostaglandin in this effect.

PMID- 18091581
TI  - Acute administration of epirubicin induces myocardial depression in isolated rat
      heart and production of radical species evaluated by electron spin resonance
      spectroscopy.
AB  - The aim of our study was to evaluate the acute effect of epirubicin (EPI), an
      anthracycline anticancer drug, on the evolution of cardiac functional parameters
      and production of reactive oxygen/nitrogen species (RONS). Isolated perfused rat
      hearts were subjected to 70 minutes of EPI (10.3 microM) infusion and to 5
      minutes of isoproterenol (ISO, 0.1 microM) at the end of the protocol. Coronary
      flow (CF), left ventricular developed pressure (LVDP), and lactate dehydrogenase
      (LDH) release in the coronary effluents were evaluated throughout the protocol.
      RONS were detected in the coronary effluents by electron spin resonance
      spectroscopy with a spin probe, 1-hydroxy-3-carboxy-pyrrolidine (CP-H, 0.1 mM).
      EPI induced a reduction in CF and in LVDP (P < 0.001). ISO infusion enhanced CF
      and RPP in the control group; in the EPI group, these increases were
      significantly impaired. Release of LDH was significantly increased during EPI
      infusion (P < 0.001). RONS was 2.5 times greater in the EPI group than in the
      control group (P < 0.05). In conclusion, a significant deterioration in cardiac
      function was observed after EPI perfusion and was associated with cellular injury
      and the generation of myocardial RONS. Further investigations are now needed to
      determine whether new cardioprotective agents targeting oxidative stress may
      reduce the incidence of anthracycline-induced cardiotoxicity.

PMID- 18091582
TI  - Calcitonin gene-related Peptide-mediated depressor effect and inhibiting vascular
      hypertrophy of rutaecarpine in renovascular hypertensive rats.
AB  - Calcitonin gene-related peptide (CGRP), the predominant neurotransmitter in
      capsaicin-sensitive sensory nerves, is a potent vasodilator and inhibits
      proliferation of vascular smooth muscle cells. Previous investigations have
      demonstrated that the hypotensive effect of rutaecarpine (Rut) is associated to
      stimulation of CGRP synthesis and release via activation of the vanilloid
      receptor subtype 1 (VR1) in the phenol-induced hypertensive rat. This study
      tested whether the depressor effect and inhibiting vascular hypertrophy of Rut is
      mediated by endogenous CGRP in 2-kidney, 1-clip (2K1C) hypertensive rats.
      Systolic blood pressure (SBP) was measured by tail-cuff method in conscious.
      Mesenteric arteries were isolated for examination of morphological changes. The
      concentration of CGRP in the plasma and the expression of CGRP mRNA in dorsal
      root ganglia (DRG) were measured. Chronic administration of Rut (10, 20, or 40
      mg/kg/day, respectively) for 4 weeks caused a depressor effect and significantly
      regressed the lumen diameter and decreased the medium thickness of mesenteric
      arteries in hypertensive rats concomitantly with an increase in the plasma
      concentration of CGRP and the expression of CGRP mRNA in DRG. In conclusion,
      chronic administration of Rut can reduce blood pressure and relieve mesenteric
      artery hypertrophy in the 2K1C hypertensive rats, and the effects of Rut may be
      related to stimulation of CGRP synthesis and release.

PMID- 18091583
TI  - S1P1-selective agonist SEW2871 exacerbates reperfusion arrhythmias.
AB  - Sphingosine-1-phosphate (S1P) has been considered to play an important role in
      ischemia/reperfusion (I/R) injury. We used SEW2871 (SEW), a novel receptor
      selective agonist for S1P1, to elucidate the role of S1P1 in myocardial I/R.
      Isolated perfused rat hearts exposed to S1P (1 and 10 mM) or SEW (1 and 0.1 mM)
      were subjected to 30 minutes of global no-flow ischemia and 2 hours of
      reperfusion. S1P at 1 and 10 mM significantly reduced infarct size and CK release
      compared with vehicle-control. The effect of 0.1 microM SEW on infarct size was
      modest. After I/R, S1P at both doses and SEW at 0.1 microM improved developed
      pressure (LVDP). SEW at 1 mM significantly prolonged the duration of ventricular
      tachycardia and ventricular fibrillation, leading to irreversible reperfusion
      tachyarrhythmias in 60% of the hearts. This is the first demonstration of the
      critical role of the S1P1 receptor in I/R injury.

PMID- 18091584
TI  - Diabetes abolishes sildenafil-induced cGMP-dependent protein kinase-I expression
      and cardioprotection.
AB  - The selective phosphodiesterase type 5 inhibitor sildenafil has been demonstrated
      to produce cardioprotection; however, diabetes is known to abolish
      cardioprotective signaling. We tested the hypothesis that sildenafil-induced cGMP
      dependent protein kinase-I (PKG-I) expression and cardioprotection are attenuated
      by diabetes. Barbiturate-anesthetized dogs (n = 38) were instrumented for
      measurement of hemodynamics and subjected to 60-minute occlusion of the left
      anterior descending coronary artery and 3-hour reperfusion. Dogs were randomly
      assigned to receive 0.9% saline (control) or intravenous sildenafil (0.7 or 1.4
      mg/kg) in the absence or presence of diabetes (3 weeks after administration of
      alloxan and streptozotocin). No differences in hemodynamics or coronary
      collateral blood flow (radioactive microspheres) were observed between groups
      before and during ischemia and reperfusion, except that infusion of sildenafil
      produced transient decreases in left ventricle systolic pressure. Sildenafil
      significantly (P < 0.05) reduced infarct size (16 +/- 2% of the left ventricular
      area at risk; triphenyltetrazolium staining) as compared to control (31 +/- 39%).
      Diabetes alone did not alter infarct size (31 +/- 2%) but abolished the
      protective effect of sildenafil (0.7 mg/kg: 26 +/- 3%; 1.4 mg/kg: 26 +/- 3%).
      Sildenafil increased PKG-I expression (immunohistochemistry and Western blotting)
      in the absence but not the presence of diabetes. The results indicate that
      diabetes abolishes cardioprotection by sildenafil and implicates PKG-I in the
      signal transduction pathway activated by this drug.

PMID- 18091585
TI  - Peroxynitrite is Involved in the dysfunction of vasorelaxation in SHR/NDmcr-cp
      rats, spontaneously hypertensive obese rats.
AB  - SHR/NDmcr-cp (SHR-cp) rats display typical symptoms and features of the metabolic
      syndrome. We previously reported that endothelium-dependent relaxation decreases
      in the thoracic aortas of SHR-cp rats, despite increased nitric oxide (NO)
      production from the endothelium. In the present study, to search for the reasons
      for this contradiction, we investigated whether vascular abnormality could be
      reduced by treatment of SHR-cp rats with antihypertensive drugs; a calcium
      channel blocker (amlodipine), an alpha 2 and imidazoline receptor agonist
      (moxonidine), and an angiotensin II type 1 (AT1) receptor antagonist
      (telmisartan). Telmisartan but not amlodipine and moxonidine ameliorated the
      impairment of relaxation in response to acetylcholine and the increased protein
      expression of endothelium NO synthase in thoracic aortas. All three drugs
      significantly lowered the blood pressure. Telmisartan decreased the serum levels
      of lipid peroxide and 8-hydroxy-2'-deoxyguanosine, oxidative stress markers, and
      also the aortic levels of the protein expression of gp91, a component of NADPH
      oxidase, and 3-nitrotyrosine, a biomarker of peroxynitrite. These findings
      suggest that NADPH oxidase-derived superoxide, probably produced due to
      stimulation of AT1 receptors, reacts with NO to form peroxynitrite, and
      consequently decreases active NO, leading to attenuation of endothelium-dependent
      relaxation. Angiotensin receptor antagonists may be effective for preventing
      endothelial dysfunction in metabolic syndrome.

PMID- 18091586
TI  - Effects of prostaglandin E1 on vascular ATP-sensitive potassium channels.
AB  - BACKGROUND: Prostaglandin E1 (PGE1) has been reported to activate ATP-sensitive
      potassium (KATP) channels, which induces vasorelaxation. However, direct evidence
      of PGE1 interactions with vascular KATP channels is limited. METHODS: The present
      study investigated the effects and mechanisms of PGE1 on vascular KATP channels
      in both isometric tension and patch clamp experiments. Isometric tension
      experiments were performed in rat thoracic aortic rings without an endothelium.
      Electrophysiologic experiments were performed using patch-clamp techniques to
      monitor KATP channels in rat vascular smooth muscle cells. RESULTS: PGE1
      significantly decreased the isometric tension in a concentration-dependent
      manner, which was partially inhibited by pretreating with a KATP channel
      inhibitor, glibenclamide (1 microM), or an inhibitor of protein kinase A (PKA),
      Rp-cAMPS (100 microM). Application of PGE1 to the bath solution during cell
      attached recordings induced a significant increase in KATP channel activity,
      whereas PGE1 failed to activate KATP channels in the inside-out patches. The PGE1
      induced KATP channel currents in cell-attached patches were abolished by
      pretreating with Rp-cAMPS (100 microM). CONCLUSIONS: The results indicate that
      the activation of vascular KATP channels played an important role in the PKA
      dependent PGE1-induced vasorelaxation. Furthermore, an electrophysiological
      experiment demonstrated that PGE1 activated vascular KATP channels via PKA
      activation.

PMID- 18091587
TI  - Inducible nitric oxide synthase attenuates adrenergic signaling in alcohol fed
      rats.
AB  - Chronic, excessive alcohol consumption is associated with myocardial dysfunction
      in humans. The molecular mechanisms and cellular signaling pathways contributing
      to this cardiac dysfunction remain largely unknown. This study examined the
      effects of chronic alcohol consumption on myocardial function and cardiac myocyte
      signaling pathways. Adult male rats were fed a commercially prepared diet
      containing either ethanol (13 g/kg/d) or isocaloric control diet for 1 month. In
      vivo hemodynamics were measured in awake rats after inserting a catheter tip in
      the left ventricle under general anesthesia. Ventricular dysfunction was
      evidenced in awake, alcohol-fed rats by increased left ventricular end diastolic
      pressure, decreased systolic developed left ventricular pressure, and decreases
      in both positive and negative dp/dt compared with controls. Cardiac myocytes
      isolated from alcohol-fed rats also demonstrated an attenuated response to the
      beta-adrenergic agonist, isoproterenol, compared to controls. This response was
      significantly reversed by the nitric oxide synthase (NOS) inhibitor, N-monomethyl
      L-arginine (L-NMMA). Western analyses confirmed inducible nitric oxide synthase
      (iNOS) protein synthesis in cardiac myocytes isolated from alcohol fed rats. It
      is therefore concluded that chronic alcohol ingestion results in iNOS-mediated
      attenuation of adrenergic signaling and depression in both systolic and diastolic
      function in rats.

PMID- 18091588
TI  - Endothelin-1 and serotonin are involved in activation of RhoA/Rho kinase
      signaling in the chronically hypoxic hypertensive rat pulmonary circulation.
AB  - We have previously reported that vasoconstrictor sensitivity to KCl (a receptor
      independent and voltage-gated Ca influx-mediated vasoconstrictor) is augmented in
      the chronically hypoxic hypertensive rat pulmonary circulation probably through
      increased Rho kinase-mediated Ca sensitization. However, the upstream mechanism
      by which the RhoA/Rho kinase signaling pathway is activated is unknown. This
      study examined if endogenous endothelin-1 (ET-1) and serotonin (5-HT) play roles
      in the Rho kinase-mediated augmented vasoconstrictor response to KCl and the
      activation of RhoA in chronically hypoxic hypertensive rat pulmonary arteries.
      The augmented KCl vasoconstriction in hypertensive lungs was reduced by the ETA
      receptor antagonist BQ123, while a dual ETA/B antagonist had no further effects.
      A combination of BQ123 and a 5-HT1B/1D receptor antagonist, GR127935, was more
      effective than either agent alone. The combined antagonists also reduced
      augmented contractile sensitivity to KCl in hypertensive intrapulmonary arteries.
      Membrane-to-cytosol ratio of RhoA expression in hypertensive arteries was greater
      than that in normotensive arteries and was reduced by BQ123 and GR127935. These
      results suggest that stimulation of ETA and 5-HT1B/1D receptors by endogenous ET
      1 and 5-HT, respectively, is involved in RhoA/Rho kinase-mediated increased Ca
      sensitization in the chronically hypoxic hypertensive rat pulmonary circulation.

PMID- 18091589
TI  - Valsartan therapy in heart failure after myocardial infarction: the role of
      endothelial dependent vasorelaxation.
AB  - Angiotensin II receptor blockade (ARB) increases vasorelaxation in heart failure
      by enhancing endothelial nitric oxide (NO). To determine the effects of valsartan
      on NO-mediated peripheral vascular function after myocardial infarction (MI), we
      treated adult male Sprague-Dawley rats immediately after MI with valsartan for 3
      weeks (sham, n = 10; MI, n = 11) and 6 weeks (sham, n = 6; MI, n = 8). At both
      time points, valsartan lowered (P < 0.05) left ventricular (LV) systolic pressure
      (103 +/- 4 and 107 +/- 4 vs. 93 +/- 3 and 85 +/- 4 mm Hg, respectively) and LV
      end-diastolic pressure (25 +/- 1 and 25 +/- 2 to 13 +/- 2 and 18 +/- 3 mm Hg,
      respectively). Valsartan lowered (P < 0.05) LV dP/dt only at 6 weeks (4676 +/-
      168 and 4503 +/- 232 vs. 4539 +/- 281 and 3372 +/- 417 mm Hg/sec); valsartan
      shortened (P < 0.05) the time constant of LV relaxation or tau only at 3 weeks
      (24.2 +/- 1.8 and 26.5 +/- 2.3 vs. 20.1 +/- 0.7 and 23.8 +/- 1.4 msec). At 6
      weeks, the vasorelaxation response to acetycholine in aortic rings was decreased
      (P < 0.05) with MI and improved at acetycholine doses (10, 10, and 10; P < 0.06)
      with valsartan. Endothelial nitric oxide synthase (eNOS) protein was undetectable
      in aortic tissue from valsartan treated rats or from aortic tissue incubated with
      valsartan (2.5, 25, and 50 mg/mL). These data suggest that valsartan improves
      cardiac function after MI by modulating LV remodeling, decreasing LV end
      diastolic pressure, and enhancing both LV diastolic and endothelial function.
      These effects are mediated, in part, by NO but upregulation of eNOS may not be
      required for improved systemic endothelial function in heart failure.

PMID- 18091590
TI  - Upregulation of angiotensin II-AT1 receptors during statin withdrawal in vascular
      smooth muscle cells.
AB  - Acute discontinuation of statins induces vascular dysfunction and increases
      cardiovascular events. The mechanisms underlying these events are under
      investigation. We showed an increase in angiotensin II (AngII) signaling after
      acute statin withdrawal. We investigated whether AngII-AT1-receptor expression
      (AT1-R mRNA) and receptor protein (AT1-R) levels mediate increased AngII
      signaling. In rat aortic vascular smooth muscle cells (VSMC), simvastatin (0.3 to
      3 microM for 24 hours) resulted in concentration-dependent inhibition of AngII
      stimulated phosphorylation of extracellular-signal regulated kinase 1/2 ERK1/2 (
      67 +/- 5% with 3 microM; P < 0.001) and decreased AT1-R mRNA (-34 +/- 8% with 3
      microM; P < 0.01) and AT1-R protein (-32 +/- 6% with 3 microM; P < 0.01). Removal
      of simvastatin led to a rebound increase in mRNA-AT1-R (+39 +/- 2%, P < 0.01),
      AT1-R protein (+46 +/- 2%; P < 0.01), and AngII-mediated phosphorylation of
      ERK1/2 (+36 +/- 3%; P < 0.01). The increase in receptor expression was present at
      1 hour and lasted for 4 hours, whereas increased AT1-R protein and AngII
      signaling started at 2 hours and lasted for nearly 2 hours. In summary, increased
      AngII signaling after statin withdrawal is most likely due to increases in AT1-R
      number due to increased transcription. The increase in AngII activity may
      contribute to the vascular dysfunction associated with statin withdrawal.

PMID- 18091591
TI  - The presentation of appendicitis in preadolescent children.
AB  - PURPOSE: We describe the clinical presentation of appendicitis in preadolescent
      children and differences in symptoms among age-stratified subgroups. METHODS:
      This is a retrospective analysis of a prospectively collected de-identified data
      set of patients 3 years or older and patients younger than 12 years presenting to
      a pediatric emergency department during a 21-month period with symptoms
      suspicious for appendicitis. The rates of appendicitis, perforation, negative
      appendectomy, as well as sensitivities, specificities, and positive likelihood
      ratios for historical and clinical variables associated with appendicitis were
      calculated for the entire cohort and for 3 age-stratified subgroups. RESULTS: Of
      379 children, 121 (32%) had appendicitis, 75 (62%) were male, 24 (20%) had a
      perforated appendix, and 16 (12%) had a negative appendectomy. The perforation
      rate was highest (53%) in the youngest subset of patients (3-5.99 years).
      Patients with appendicitis presented with inability to walk (82%), maximal right
      lower quadrant tenderness (82%), nausea (79%), pain with percussion, hopping,
      coughing (79%), and anorexia (75%). Fewer patients with appendicitis presented
      with a history of vomiting (66%), fever (47%), or diarrhea (16%), and these
      findings were not associated with the diagnosis. The youngest subset of patients
      (3-5.99 years) presented to the emergency department with fever; however, within
      this age subset, there was no significant difference in temperatures between
      patients with and without appendicitis. Fever was an indicator for perforation.
      Psoas, Rovsing, and obturator signs were infrequent but very specific for
      appendicitis (0.86-0.98 depending on age). CONCLUSIONS: Nausea, right lower
      quadrant tenderness, inability to walk, and elevated white blood cell and
      neutrophil counts are sensitive indicators of appendicitis in preadolescent
      children. Although peritoneal signs are infrequently elicited, when present, they
      substantially increase the likelihood of appendicitis. Fever, vomiting, and
      diarrhea are not associated with appendicitis in preadolescent children.

PMID- 18091592
TI  - Does length-based resuscitation tape accurately place pediatric patients into
      appropriate color-coded zones?
AB  - OBJECTIVE: To determine relationship between length-based resuscitation tape
      (LBT)-based color-coded zones and actual weight-based color-coded zones. METHODS:
      Data were retrospectively abstracted from 839 patients in Rochester, Minnesota,
      at birth, 4 to 6, and 10 to 12 years. Height was plotted on LBT to determine
      estimated weight and corresponding color zone. Patient's weight-based color zone
      was obtained by plotting measured weight on LBT. Degrees of discrepancy between
      length-based and actual weight-based color zones were assessed. RESULTS: Total of
      544, 520, and 143 subjects were analyzed at birth, 4 to 6, and 10 to 12 years,
      respectively, with a subset of 103 subjects measured longitudinally at more than
      1 age strata. Among infants, all LBT color zones were the same as actual weight
      based color zones. In children aged 4 to 6 years, 70% (n = 361) of LBT-estimated
      color zones were the same as actual weight-based color zones; LBT underestimated
      19% (n = 99) by 1 color zone, 0.5% (n = 3) were underestimated by 2 color zones,
      0.5% (n = 3) exceeded weight limit on LBT, and 10% (n = 54) were overestimated by
      1 color zone. In adolescents aged 10 to 12 years, 40.6% (n = 58) of LBT-estimated
      color zones were the same as actual weight-based color zones; LBT underestimated
      3.5% (n = 5) by 1 color zone, 44.1% (n = 63) exceeded weight limit on LBT, 11.2%
      (n = 16) were overestimated by 1 color zone, and 0.6% (n = 1) were overestimated
      by 2 color zones. CONCLUSIONS: Overall, LBT reasonably estimates appropriate
      color zones for drug dosing. However, LBT tends to underestimate color zones
      among younger obese children and adolescents. Potential implications of the
      rising trend of overweight children on resuscitation practice and drug
      administration must be considered.

PMID- 18091593
TI  - A survey of emergency department management of acute urticaria in children.
AB  - OBJECTIVES: To describe emergency department management of acute urticaria in
      children and to determine factors associated with management strategies and
      adherence to practice guidelines. METHODS: Self-administered cross-sectional
      survey mailed to all Section of Emergency Medicine members of the American
      Academy of Pediatrics (n = 1190) and 1000 randomly selected members of the
      American College of Emergency Physicians. Main outcome measure was proportion of
      respondents adhering to published guidelines. Factors associated with management
      strategies were analyzed using bivariate and logistic regression analyses.
      RESULTS: Of 2190 surveys sent, 1137 (52.5%) were available for analysis.
      Respondents included 44.6% pediatric emergency physicians, 36.4% emergency
      physicians, and 15.3% pediatricians. First-generation histamine (H)1 antagonists
      alone were the most common therapy used on initial presentation of acute
      urticaria, followed by corticosteroids, H2 antagonists, and second-generation H1
      antagonists, used by only 7.8%, despite their recommendation as first-line
      therapy. Physicians working in an emergency department as opposed to an urgent or
      primary care setting were less likely to use second-generation H1 antagonists
      (odds ratio [OR], 0.3 [0.1-0.7]). General emergency physicians were 2.6 times
      more likely to use H2 antagonists and more than 3 times as likely to use
      corticosteroids. Only 14.2% of physicians overall were familiar with guideline
      recommendations. CONCLUSIONS: Minimal awareness and use of existing guidelines,
      and low concordance with published recommendations exist. Management practices
      vary and are influenced by training, practice setting, and clinical experience.

PMID- 18091594
TI  - Knowledge of procedural sedation and analgesia of emergency medicine physicians.
AB  - OBJECTIVES: Pediatric procedural sedation and analgesia (PSA) is unique. The
      goals of this study were to examine emergency medicine (EM) physicians' baseline
      knowledge of general and pediatric PSA compared with that of other
      nonanesthesiologist physicians and to test effectiveness of a seminar required
      for credentialing in PSA. METHODS: This was a retrospective, before and after
      interventional study of participants in a major university teaching hospital's
      PSA course. Analysis was conducted to determine: (1) performance of EM physicians
      on questions related to general and pediatric PSA compared with other
      participating physicians, and (2) effect of seminar on participants' knowledge of
      PSA. RESULTS: The mean +/- SE PSA pretest score for EM physicians was higher than
      that of other physicians (63.7% +/- 1.1% vs 50.2% +/- 2.2%, P < 0.001), but not
      for the pediatric PSA pretest scores (54.8% +/- 1.7% vs 51.0% +/- 1.8%, P =
      0.17). The EM practitioners performed worse on the pediatric versus the adult
      portion of the PSA pretest (55.2% +/- 1.8% vs 66.8% +/- 1.4%, P < 0.001).
      Practitioners trained in American Heart Association advanced life support classes
      performed better than the untrained (52.1 +/- 1.4 vs 41.6+/- 2.5, P < 0.001).
      Total and pediatric PSA test scores improved significantly after educational
      intervention in all practitioners. CONCLUSIONS: The EM physicians have stronger
      knowledge about general PSA than other nonanesthesiologist physician
      participants, but not for pediatric PSA, thus providing a target for future
      interventions. This course on PSA improved practitioners' knowledge of general
      and pediatric PSA and can be used as an educational model for PSA training.
      Further study is needed to determine decay rates for this knowledge and impact on
      patient care.

PMID- 18091595
TI  - Standard precautions in the pediatric emergency department: knowledge, attitudes,
      and behaviors of pediatric and emergency medicine residents.
AB  - OBJECTIVES: To determine if pediatric residents (PRs) and emergency medicine
      residents (EMRs) differ in their knowledge, attitudes, and behaviors about
      standard precautions (SPs) in the pediatric emergency department and to identify
      any differences in perceived obstacles to adherence to SPs. METHODS: A cross
      sectional survey of PRs and EMRs from 1 program was conducted. The survey
      addressed 4 domains: knowledge, attitudes, behaviors, and obstacles to adherence
      to SPs. RESULTS: Seventy-five percent of PRs (80/106) and 80% of EMRs (28/35)
      responded to the survey. There were no significant differences identified in
      knowledge or attitudes about SPs. A significantly lower proportion of PRs
      reported compliance with using face masks (28% vs 56%, P = 0.01) and eye shields
      (34% vs 56%, P = 0.05) during at least 95% of all irrigations and using face
      masks (30% vs 66%, P = 0.001) and eye shields (31% vs 60%, P = 0.01) for at least
      95% of all incision and drainage procedures. A significantly higher proportion of
      EMRs reported using gloves at least 95% of the time for venipuncture and
      intravenous catheter placement (84% vs 58%, P = 0.04). The following were
      identified as more likely to be an obstacle for PRs: interference of blood
      drawing device with technical skill (74% vs 50%, P = 0.03), unsure which
      protective barrier to use (59% vs 32%, P = 0.01), and lack of familiarity with
      newer devices (75% vs 50%, P = 0.01). CONCLUSIONS: The PRs report more unsafe
      practices than EMRs. Many of the obstacles noted by all residents are easily
      remedied.

PMID- 18091596
TI  - Ketamine-propofol combination sedation for fracture reduction in the pediatric
      emergency department.
AB  - OBJECTIVES: To evaluate the time of onset and recovery from and the efficacy and
      safety of intravenous ketamine-propofol sedation for reduction of forearm
      fractures in the pediatric emergency department setting. STUDY DESIGN:
      Prospective, observational pilot study. METHODS: Children presenting to an urban
      pediatric emergency department requiring sedation for closed reduction of forearm
      fractures received ketamine 0.5 mg/kg and propofol 1 mg/kg. We measured time
      intervals from drug administration to reduction, recovery, and attainment of
      discharge criteria, and obtained ratings of depth of sedation, pain, and ease of
      reduction. A follow-up survey elicited patient recall, parental satisfaction, and
      delayed complications. Complications were recorded during the procedure and by
      chart review. RESULTS: Reduction was successful in 19 of 20 patients with one
      requiring open reduction. Median time intervals measured from initiation of
      ketamine injection were 5 minutes to reduction completion, 10 minutes to first
      purposeful response, and 38 minutes to suitability for discharge. Three patients
      recalled reduction or casting, but in no case was reduction reported to be the
      most painful aspect of visit. Emergency physicians and orthopedic residents rated
      sedation and ease of reduction favorably. Complications included mild hypoxia,
      vomiting, and transient ataxia. No apnea, hemodynamic compromise, dysphoria, or
      injection pain occurred. CONCLUSIONS: In this pilot study, the combination of
      ketamine and propofol provided effective sedation with rapid recovery and no
      clinically significant complications for children requiring closed reduction of
      forearm fractures.

PMID- 18091597
TI  - Dancing eyes, dancing feet: opsoclonus-myoclonus in an 18-month-old child with
      neuroblastoma.
AB  - Opsoclonus-myoclonus-ataxia syndrome is a rare disorder frequently associated
      with neuroblastoma in pediatric patients. We present the case of an 18-month-old
      child with symptoms classic of the syndrome and review the current literature
      with the aim of aiding the clinician in the recognition and early management of
      this disease.

PMID- 18091598
TI  - Late onset of spontaneous pneumothorax complicating acute bronchiolitis in a 5
      month-old infant: case report and literature review.
AB  - The literature contains only a few reported cases of spontaneous pneumothorax
      complicating acute bronchiolitis in infants. We present a case of a 5-month-old
      infant with a presentation of spontaneous pneumothorax 7 days after
      hospitalization for acute bronchiolitis. The characteristics of this particular
      manifestation are discussed.

PMID- 18091599
TI  - An upper airway obstruction emergency: Ludwig angina.
AB  - Ludwig angina remains a potentially lethal disease, rapidly spreading bilateral
      cellulitis of the submental, sublingual, and submandibular spaces, which bears
      the threat for rapid airway obstruction. Since the introduction of antibiotics in
      1940s, the mortality was reduced significantly. This resulted in the rare
      occurrence of the disease, leaving many physicians with limited experience of
      Ludwig angina. Although the occurrence of Ludwig angina in adults is rare, its
      presence in the pediatric edentulous population is even more uncommon. Because
      the unfamiliarity with this disease is now increasing, unnecessary delaying
      diagnosis or inadequate management may occur and may result in serious
      complications. This presentation will consist of a historical review, discussion
      of pathophysiology, followed by clinical presentation, etiology, bacteriology,
      and management. With early diagnosis, airway observation and management,
      aggressive intravenous antibiotic therapy, and judicious surgical intervention,
      the disease should resolve without complications. In addition, the source of
      infection should be determined and eliminated if possible. A thoughtful,
      individualized management strategy seems to be the most reasonable approach to
      the disease.

PMID- 18091600
TI  - The missing "Bratz" doll: a case of vaginal foreign body.
AB  - Young female patients with gynecologic complaints, including vaginal discharge,
      commonly seek care in the emergency department. Prepubertal vaginal discharges
      have various potential etiologies including nonspecific vulvovaginitis,
      infections, inflammatory or dermatologic processes, precocious puberty,
      malignancy, anatomical anomaly, trauma, sexual abuse, and foreign body. We
      present the case of a 4-year-old girl with vaginal odor and discharge secondary
      to a foreign body. The foreign body was part of a toy, the lower half of the
      patient's missing "Bratz" (MGA Entertainment) doll. Although it is well known
      that a vaginal foreign body can cause a vaginal discharge, the unusual nature of
      the foreign body in this case and the revealing radiograph made this a case of
      particular interest.

PMID- 18091601
TI  - Pediatric emergency medicine: legal briefs.

PMID- 18091602
TI  - The new insulins.
AB  - Diabetes is a growing problem for a large proportion of children. Insulin is the
      primary medication used for most cases of pediatric diabetes, though achieving
      adequate glycemic control with current insulin products can be extremely
      challenging. New insulin forms, including novel analogues and radically changed
      delivery systems are providing new approaches to controlling diabetes. Health
      care providers caring for patients with diabetes must be informed of the new
      insulins becoming available to patients. This CME article will provide an
      introduction to some of the new insulins and delivery systems.

PMID- 18091604
TI  - A 6-year-old girl with somnolence: patching together the clues.

PMID- 18091605
TI  - ECGs in the ED.

PMID- 18091606
TI  - Oropharyngeal injuries in children.
AB  - BACKGROUND: Oral cavity and oropharyngeal injuries are common among pediatric
      patients seen in emergency rooms for head and neck trauma. The appropriate
      treatment of such injuries is often controversial. PATIENTS AND METHODS: Audit of
      6 months' admissions to the pediatric emergency room in a secondary care referral
      center. Sixty-four patients were treated for various injuries. Charts were
      reviewed for relevant data. RESULTS: Description of distribution of types and
      sites of injuries and discussion of treatment recommendations. CONCLUSIONS: Most
      of oropharyngeal injuries heal without any intervention and therefore can be left
      untreated after being diagnosed. However, in certain injuries, treatment is
      indicated for better outcome results.

PMID- 18091608
TI  - Enfuvirtide does not require dose adjustment in patients with chronic kidney
      failure: results of a pharmacokinetic study of enfuvirtide in HIV-1-infected
      patients with impaired kidney function.
AB  - OBJECTIVE: The aim of this study was to examine the influence of kidney disease
      and hemodialysis on the pharmacokinetics ofenfuvirtide. DESIGN: An open-label,
      multicenter, parallel group study of HIV-1-infected patients with varying degrees
      of kidney dysfunction. METHODS: A 90-mg dose of enfuvirtide was administered by
      subcutaneous injection to 3 groups of patients: group A, patients with normal
      kidney function; group B, patients with chronic kidney disease; and group C,
      patients with end-stage renal disease (ESRD) requiring dialysis. Patients with
      ESRD requiring dialysis received the 90-mg dose of enfuvirtide on 2 separate
      occasions; a dialysis day and a nondialysis day. After each dose, a full 48-hour
      pharmacokinetic profile was collected and pharmacokinetic parameters were
      estimated using model-independent techniques. RESULTS: Enfuvirtide area under the
      curve (AUCinfinity) and maximum observed enfuvirtide plasma concentration (Cmax)
      for patients with normal kidney function (group A) was 49.6 microg h/mL and 3.79
      microg/mL, respectively. Patients with chronic kidney disease (group B) had
      higher AUCinfinity (80.3 microg h/mL) and Cmax (5.72 microg/mL), which was
      similar to patients with ESRD (group C) on both nondialysis days (AUCinfinity
      71.1 microg h/mL; Cmax 5.34 microg/mL) and dialysis days (AUCinfinity 66.9 microg
      h/mL; Cmax 6.31 microg/mL). An average of< 13% of enfuvirtide was removed during
      the dialysis procedure. The incidence of adverse events was comparable for all
      study groups. CONCLUSION: Enfuvirtide exposure observed in patients with ESRD
      requiring dialysis or chronic kidney disease was slightly higher than in patients
      with normal kidney function and similar to historical Cmax and AUC values from
      studies in patients with normal kidney function. Thus, enfuvirtide does not
      require dosage adjustment in patients with impaired kidney function.

PMID- 18091611
TI  - Notes from the net nomad.

PMID- 18091609
TI  - Effects of depression and selective serotonin reuptake inhibitor use on adherence
      to highly active antiretroviral therapy and on clinical outcomes in HIV-infected
      patients.
AB  - OBJECTIVES: To determine the impact of depression on highly active antiretroviral
      therapy (HAART) adherence and clinical measures and investigate if selective
      serotonin reuptake inhibitors (SSRIs) improve these measures. DESIGN:
      Retrospective cohort study. METHODS: In 2 large health maintenance organizations,
      we measured the effects of depression (with and without SSRI use) on adherence
      and changes in viral and immunologic control among HIV-infected patients starting
      a new HAART regimen. HAART adherence, HIV RNA levels, and changes in CD4 T-cell
      counts through 12 months were measured. RESULTS: A total of 3359 patients were
      evaluated; 42% had a depression diagnosis, and 15% used SSRIs during HAART.
      Depression without SSRI use was associated with significantly decreased odds of
      achieving > or =90% adherence to HAART (odds ratio [OR] = 0.81, 95% confidence
      interval [CI]: 0.70 to 0.98; P = 0.03). Depression was associated with
      significantly lower odds of an HIV RNA level <500 copies/mL (OR = 0.77, 95% CI:
      0.62 to 0.95; P = 0.02). Depressed patients compliant with SSRI medication (>80%
      adherence to SSRI) had HAART adherence and viral control statistically similar to
      nondepressed HIV-infected patients taking HAART. Comparing depressed with
      nondepressed HIV-infected patients, CD4 T-cell responses were statistically
      similar; among depressed patients, those compliant with SSRI had statistically
      greater increases in CD4 cell responses. CONCLUSIONS: Depression significantly
      worsens HAART adherence and HIV viral control. Compliant SSRI use is associated
      with improved HIV adherence and laboratory parameters.

PMID- 18091612
TI  - A model for incorporating technology into student nurse clinical.

PMID- 18091613
TI  - An academic-industry partnership for advancing technology in health science
      education.

PMID- 18091614
TI  - A collaborative model to ensure graduating nurses are ready to use electronic
      health records.

PMID- 18091615
TI  - Student usage of electronic medical record.

PMID- 18091616
TI  - Including information technology project management in the nursing informatics
      curriculum.
AB  - Project management is a critical skill for nurse informaticists who are in
      prominent roles developing and implementing clinical information systems. It
      should be included in the nursing informatics curriculum, as evidenced by its
      inclusion in informatics competencies and surveys of important skills for
      informaticists. The University of Pennsylvania School of Nursing includes project
      management in two of the four courses in the master's level informatics minor.
      Course content includes the phases of the project management process; the
      iterative unified process methodology; and related systems analysis and project
      management skills. During the introductory course, students learn about the
      project plan, requirements development, project feasibility, and executive
      summary documents. In the capstone course, students apply the system development
      life cycle and project management skills during precepted informatics projects.
      During this in situ experience, students learn, the preceptors benefit, and the
      institution better prepares its students for the real world.

PMID- 18091618
TI  - One strategy to reduce medication errors: the effect of an online continuing
      education module on nurses' use of the Lexi-Comp feature of the Pyxis MedStation
      2000.
AB  - This study sought to evaluate the impact of an online self-learning module on
      nurse knowledge and use of the Lexi-Comp feature of the Pyxis MedStation Rx 2000
      system, a point-of-care medication delivery system. Data were collected among
      nurse-users at a community-based healthcare organization (N = 41). Pre- and post
      training surveys were used to evaluate training effects. After training,
      completion of the tutorial and knowledge and use of the Lexi-Comp feature
      increased by 23% and 56%, respectively. One month after training, a drop in
      medication errors on administration at the healthcare organization was observed.
      These findings suggest that use of evaluative and instructional tools would
      improve integration of technology and clinical practice and improve patient
      outcomes in medication error reduction.

PMID- 18091619
TI  - Developing a wireless speech- and touch-based intelligent comprehensive triage
      support system.
AB  - The implementation of voice recognition technology has been expected to occur in
      mobile healthcare settings, but it is the least studied solution in nursing. The
      objective of this study is to examine its value to mobile nursing. The study was
      done at a triage station in an emergency department. The system was developed
      using VB6.0, Microsoft Speech SDK 5.1 and the Simplified Chinese Language pack,
      and was installed on touchscreen PCs with wireless headsets. Thirty nurses were
      enrolled. Accuracy rate and operation time were used to measure the subjects'
      performance. A "willingness to use" score on a scale of 1 to 10 was used to
      measure subjects' preference for the system. The results showed that the average
      accuracy rate was 99%, the average operation time was 108 seconds, and the mean
      "willingness to use" rating was 8.2. This study demonstrates the value of
      multimodal voice recognition techniques to mobile nursing.

PMID- 18091620
TI  - Characteristics of midlife women recruited through internet communities/groups.
AB  - The purpose of this study was to explore demographic characteristics of a
      specific online population, midlife women recruited through Internet communities
      or groups, and to provide future direction for Internet research among midlife
      women. Using a feminist perspective, the study focused on ethnic variations in
      the characteristics of the midlife women. A total of 192 midlife women were
      recruited through Internet communities. The Internet survey included questions on
      sociodemographic characteristics and health/illness status. The data were
      analyzed using descriptive and inferential statistics. The findings indicated
      that midlife women recruited through Internet communities tended to be white,
      young, married, and affluent. The findings also indicated significant ethnic
      differences in sociodemographic characteristics. The findings suggest that
      researchers need to consider that midlife women recruited from Internet
      communities tend to be a specific group of midlife women.

PMID- 18091621
TI  - Late effects of treatment for long-term cancer survivors: qualitative analysis of
      an online support group.
AB  - Ten million cancer survivors in the United States are at increased risk for
      developing late effects of treatment. Due to a lack of consistent follow-up care,
      many long-term cancer survivors use the Internet as a source of information and
      support. Research on online support for this cohort is lacking. The purposes of
      this study were to identify major themes related to long-term cancer survivorship
      and report late effects of treatment as described by members of an online support
      group. A qualitative descriptive method was utilized. Seventy-five long-term
      cancer survivors posted 300 messages online during an 8-week period and reported
      a wide variety of late effects. Three categorical schemes were identified:
      information exchange, symptomatology, and frustration with healthcare providers.
      Cancer survivors are utilizing Internet resources to find health-related
      information and support that has not been provided by healthcare providers.
      Additional research is needed to generate knowledge about the role of online
      support for long-term cancer survivors.

PMID- 18091622
TI  - Technology informatics guiding education reform: TIGER Phase 2: Achieving the
      vision.

PMID- 18091623
TI  - The 1st World Nursing Informatics Leadership Conference.

PMID- 18091624
TI  - Transfusion-related acute lung injury: a clinical challenge.
AB  - Transfusion-related acute lung injury is a life-threatening clinical syndrome. In
      the last 3 years, it has become the leading cause of reported transfusion-related
      deaths in the United States. This syndrome is characterized by acute hypoxemia
      and noncardiogenic pulmonary edema directly linked in time to a blood
      transfusion. All types of blood products have been implicated in transfusion
      related acute lung injury, but transfusion of plasma-containing products from
      multiparous women seems to carry the highest risk. The purpose of this article is
      to raise awareness of this syndrome for the critical care nurse. This article
      discusses the widely accepted clinical features of transfusion-related acute lung
      injury, its pathogenesis, differential diagnosis, and treatment.

PMID- 18091626
TI  - Using the Synergy Model as best practice in endotracheal tube suctioning of
      critically ill patients.
AB  - Endotracheal suctioning with normal saline is a common practice in intensive care
      units. This unit reviews research concerning this practice as well as the adverse
      effects of saline instillation. In addition, the role of the critical care nurse
      as it pertains to the synergy model when caring for these patients is
      highlighted.

PMID- 18091630
TI  - The life and impact of Florence Nightingale.
AB  - All nurses learn about Florence Nightingale sometime during their academic
      studies. Miss Nightingale, even though she lived over a century ago, still
      impacts current nursing care. This article provides a brief biographical review
      of her life and her impact on present day patient care.

PMID- 18091628
TI  - Spirituality: a dimension of holistic critical care nursing.
AB  - Although many patients face significant physical needs, their mind and spirit may
      be ill as well. Three facets make up an individual: physical, mental, and
      spiritual. To provide optimal holistic care, the critical care nurse must take
      into consideration each of these three aspects. But most importantly, the
      critical care nurse must recognize that spiritual care begins with oneself.
      Spirituality is one such area of patient care that, when addressed, can reap
      positive benefits for both the client and the healthcare provider. This article
      explores all aspects of spirituality for the critical care nurse.

PMID- 18091631
TI  - Comparing tympanic temperatures in both ears to oral temperature in the
      critically ill adult.
AB  - Tympanic temperatures are often used in the critical care units to measure core
      body temperatures when pulmonary artery catheters are not available. This study
      was conducted to compare tympanic temperatures in the right and left ear with
      oral temperatures. The findings of this study show that choosing the optimal site
      for each patient and using patient-specific site consistently would result in
      better tracking of changes in temperature and, thus, timely diagnosis of fever.

PMID- 18091633
TI  - Assessment of attitudes of intensive care unit staff toward clinical practice
      guidelines.
AB  - Although studies on the implementation and adherence to specific practice
      guidelines have been proliferating, research examining the attitude of healthcare
      workers toward practice guidelines in general has been lacking. This study is a
      secondary analysis of data collected from 39 volunteer hospitals participating in
      the National Nosocomial Infection Surveillance System on attitudes of intensive
      care unit staff regarding practice guidelines in general. Age, profession, type
      of intensive care unit, and race were identified as significant predictors of
      attitude scores in this study. Understanding the differences in perceived
      barriers is important for the adherence to practice guidelines.

PMID- 18091638
TI  - A healthy work environment.

PMID- 18091639
TI  - Effect of primary coronary intervention on heart rate variability and left
      ventricular function in patients with acute myocardial infarction.
AB  - AIM: Several studies showed that primary percutaneous coronary interventions
      (PCI) have a favourable impact on left ventricular remodeling and heart rate
      variability (HRV) both at short- and long-term follow-up in patients suffering an
      acute myocardial infarction (AMI). However, no previous study investigated the
      relationship between left ventricular remodeling and changes in HRV during follow
      up in AMI patients treated by primary PCI. METHODS: We studied 28 patients with
      AMI (57+/-8 years, 27 men), treated by PCI within 12 hours of symptom onset.
      Patients underwent a 24-hour ECG Holter recording and left ventricular ejection
      fraction (LVEF) echocardiographic assessment before discharge, and at 1-month and
      6-month follow-up. HRV was measured in the time- and frequency-domain. RESULTS: A
      significant improvement of both time- and frequency-domain HRV variables was
      observed at 1-month and at 6-month follow-up with the most significant changes
      being found for standard deviation of normal-normal beat intervals (SDNN) in the
      time-domain (95.5+/-26.1 ms vs 125.5+/-29.8 ms vs 142.8+/-28.8 ms, respectively;
      P<0.001) and for very low frequency (VLF) amplitude in the frequency-domain
      (36.7+/-9.8 ms vs 44.1+/-11.1 vs 48.9+/-12.2 ms, respectively; P<0.001). In
      contrast, compared to basal values, LVEF was substantially unchanged at 1-month
      and 6-month follow-up (48.8+/-8.5% vs 50.8+/-10% vs 49.6+/-9%, respectively;
      P=0.25). At 6-month follow-up 11 patients showed an improvement of >or= 5% of
      LVEF, whereas 17 patients did not show any improvement of LVEF. HRV variables
      significantly improved in a similar way in these two subgroups both at 1-month
      and at 6-month follow-up. CONCLUSION: Our data demonstrate that, in AMI patients
      treated by primary PCI, HRV improves over time, independent of changes in LVEF.
      The clinical implications of these findings deserve to be addressed in future
      studies.

PMID- 18091640
TI  - Assessment of left ventricular systolic dysfunction by tissue Doppler imaging to
      detect subclinical cardiomyopathy early after anthracycline therapy.
AB  - AIM: Anthracycline (ANT) chemotherapy for breast cancer, while associated with
      high response rates, is fraught by risks of irreversible cardiotoxicity.
      Unfortunately means to detect such cardiotoxicity early on and at a sublinical
      stage are lacking. We evaluated the role of systolic tissue Doppler imaging (TDI)
      in appraising postchemotherapy left ventricular (LV) remodelling. METHODS:
      Patients undergoing ANT-chemotherapy for breast cancer were enrolled, and
      underwent baseline and >6-months echocardiography (standard and TDI). According
      to the pattern of LV-TDI systolic remodelling from baseline to follow-up,
      patients were stratified in: group 1 (no LV-TDI worsening), group 2 (minor LV-TDI
      worsening), and group 3 (major LV-TDI worsening). Fifty-six patients were
      included (follow-up 9+/-6 months). RESULTS: At baseline, no patient had abnormal
      LV ejection fraction (LVEF), LV-TDI systolic dysfunction or New York Heart
      Association (NYHA) >1. Follow-up overall analysis showed significant
      deterioration in LVEF, end-diastolic diameter (EDD) end-systolic diameter (ESD),
      and TDI-systolic parameters (all P<0.05). Specifically, 29 (51.8%) patients
      showed no adverse LV-TDI systolic remodelling, while 17 (30.4%) were in group 2,
      and 10 (17.9%) in group 3. All groups shared similar conditions at baseline.
      Patients with adverse LV-TDI remodelling had significant increases in EDD and
      ESD, as well as a significantly decreased LVEF (all P<0.05). No patient in group
      1 had abnormal LVEF at follow-up, while 1 patient in group 2 and 2 patients in
      group 3 had abnormal LVEF (P<0.05). CONCLUSION: Subclinical systolic dysfunction
      occurs in almost 50% of patients early after chemotherapy for breast cancer, with
      a more adverse by LV-TDI remodelling implying a more pronounced deterioration of
      standard echocardiographic parameters.

PMID- 18091642
TI  - Echocardiographic evaluation of left ventricular diastolic function: correlation
      between echocardiographic and hemodynamic parameters.
AB  - AIM: The aim of this study was to assess the correlation between non invasive
      echo-Doppler parameters of diastolic function and invasively measured end
      diastolic left ventricular (LV) filling pressures in patients with normal or
      depressed LV function. METHODS: The patient population was composed of 44
      subjects, (34 men and 10 women) 52% with normal ventricular function, who
      underwent echo-Doppler and hemodynamic evaluation within 24 hours between the two
      exams. RESULTS: LV end-diastolic pressure was statistically different (P=0.022)
      in the 4 subgroups divided on the basis of the mitral flow pattern in the overall
      population and in the patients with depressed LV function, but not in those with
      normal LV function. In the overall population LV end-diastolic pressure was
      significantly correlated with: 1) E/A ratio of mitral flow (r=0.45, P=0.002); 2)
      mitral E wave peak velocity (r=0.39, P=0.017); 3) isovolumic relaxation time (r=
      0.34, P=0.01); 4) left atrial diameter (r=0.33, P=0.037); 5) duration of
      retrograde A wave of pulmonary venous flow (r=0.33, P=0.03); 6) Pulmonary vein D
      wave peak velocity (r=0.29, P=0,05). Multivariate analysis showed that the
      correlation between the echo-Doppler variables and LV end-diastolic pressure was
      statistically significant only in patients with depressed LV function, but not in
      those with normal function. CONCLUSION: Among the echo-Doppler variables
      examined, those derived from transmitral flow and pulmonary vein flow show the
      best correlation with left ventricular end-diastolic pressure; however, the
      correlation is statistically significant only in patients with depressed LV
      function. Thus, the echo-Doppler evaluation of LV diastolic function should take
      into account this limitation and should be based on a multiparametric approach.

PMID- 18091641
TI  - Stem cells mobilization in acute myocardial infarction (stem-AMI trial):
      preliminary data of a perspective, randomized, single blind trial.
AB  - AIM: Clinical trials demonstrated that granulocyte colony-stimulating factor (G
      CSF) administration seems to be safe in patients with acute myocardial infarction
      but the results about the effectiveness are not so encouraging. The main problem
      is to distinguish the effects that early revascularization and regenerative
      therapy have on left ventricular (LV) function. The purpose of our perspective
      randomized trial is to evaluate the efficacy of G-CSF administration, assessed by
      improvement of LV ejection fraction by cardiac magnetic resonance imaging (MRI),
      in patients with acute anterior myocardial infarction undergoing primary
      percutaneous coronary intervention (PCI) and with evidence of LV dysfunction.
      METHODS: Fifty consecutive patients with first anterior ST-elevation myocardial
      infarction (STEMI), undergoing primary PCI, with symptom to balloon >2 and <12
      hours and ejection fraction (EF) =or<45%, are randomized to 150 microg/m2 G-CSF
      bis in die subcutaneously (from day 0 to day 4) in addition to standard care.
      Patients are submitted to echocardiography, Holter monitoring, gated single
      photon emission computed tomography (SPECT) and MRI at baseline and at 6 months
      of follow up. Coronary angiogram is repeated at 6 months to evaluate in-stent
      restenosis. RESULTS: From July 2006 until August 2007, 13 consecutive patients
      were enrolled and 5 of them were assigned to G-CSF administration. All patients
      underwent PCI and stenting of left anterior descending artery. Mean baseline EF
      evaluated by echocardiography, SPECT and MRI was respectively 36%, 33% and 38%.
      No adverse events were observed during G-CSF administration. The mean white blood
      cells count, in the treatment arm, was 36.1 x 10(9)/L +/- 2.90 on day 5.
      CONCLUSION: Preliminary data of our study do not support any conclusive result.
      However, the characteristics of our population could allow us to distinguish the
      effects that revascularization and regenerative therapy have on LV function in
      patients with acute myocardial infarction.

PMID- 18091643
TI  - Effectiveness of mesoglycan in patients with previous deep venous thrombosis and
      chronic venous insufficiency.
AB  - AIM: Retrospective analysis of mesoglycan therapeutic activity in venous
      disorders. The clinical data have been selected from the outpatient database of
      the Chair of Angiology of the University of Catania (from 1988 to 1997) through a
      cross survey between the prescription commercial name of mesoglycan and the key
      words varicose veins, deep venous thrombosis (DVT), chronic venous insufficiency
      (CVI), post-thrombotic syndrome (PTS), venous thrombosis, venous ulcer. METHODS:
      Patients have been selected on the basis of definite data relative to principal
      diagnosis, clinical history, clinical and instrumental objective phlebological
      picture, posology and duration of treatment, follow-up visits in the first three
      years following the first observation. Group 1: 56 patients with first episode
      DVT; Group 2: 27 patients with recurrent DVT; Group 3: 182 patients with CVI (107
      with primitive CVI and 75 with secondary CVI). The selected patients data have
      been included in new databases. DVT patients were evaluated for recurrence
      prevalence during the follow-up period (6, 12, 18, 24, 30 and 36 months). In
      Group 2 the recurrence prevalence in the normal follow-up period was evaluated
      and, in addition, the clinical chronology of the recurrence previous to
      observation was drawn, in order to find out the recurrence prevalence of the
      thrombotic episode preceding our observation. The two prevalence trends (
      mesoglycan treatment and episode preceding our observation) have been compared
      with the Student t test. CVI patients (Group 3) were classified according to CEAP
      classification criteria. The effectiveness of treatment was assessed according to
      the changes in the scores of venous dysfunction of CEAP classification
      (disability score; pain; oedema; skin color change; cutaneous ulcer). The mean
      and standard deviation of the considered scores have been evaluated with the
      Student t test comparing each series with the immediately previous series and
      with the T0 series. The mean dose of mesoglycan was 50 mg twice per day. RESULTS:
      Group 1 (1(st) episode DVT): the recurrence prevalence was 3.5% at 6 months, 9%
      at 12 months, 12.5% at 18 months, 14.28% at 24, 30 and 36 months. At the end of
      the 3 follow-up years the PTS diagnosis could be performed in 10 patients
      (17.85%). Group 2 (recurrent DVT): the recurrence prevalence was 3.7% at 6
      months, 11.11% at 12 months, 14.81% at 24 months, 18.51% at 36 months during
      mesoglycan treatment. In the preceding period the prevalence was 11.11% at 6
      months from the preceding episode, 16.66% at 12 months, 33.33% at 24 months and
      37.03% at 36 months. In the remaining 62.96% the recurrence occurred at 36 and 48
      months. The comparison between the two series showed a significant difference
      with P < 0.0004. PTS prevalence at the end of the 3 follow-up years was 17.85% in
      patients with a first episode of DVT and 81.41% in patients with recurrent DVT.
      Group 3 (CVI): all the venous dysfunction scores showed a significant improvement
      during the follow-up period, both in comparison with the beginning of treatment
      and with the immediately preceding control visit. CONCLUSION: The results
      obtained in groups 1 and 2 show that mesoglycan is effective in preventing
      thrombotic recurrence in patients with previous DVT. The recurrence prevalence in
      patients with DVT at 1(st) episode was lower than the prevalence reported by the
      literature data (17.5% within 2 years and 24.6% within 5 years). The positive
      trend was also confirmed in the recurrent DVT group, although with a major
      prevalence (18.51%) due to a higher thrombotic risk. However, the prevalence in
      the treatment period is significantly lower than the previous thrombotic episode.
      Mesoglycan was also effective in CVI patients, with a progressive and significant
      improvement of disability, pain and edema, which are the pathophysiologic
      elements responsible for the impairment of quality of life. At the various follow
      up points the mean score value significantly reduced compared to T0 and to the
      values of the preceding control. In conclusion mesoglycan is a useful and
      effective medication in the treatment of venous disorders, both in the subacute
      phase of DVT and in the long-term therapy for CVI, and is worth more extensive
      documentation, in accordance with the criteria of evidence-based medicine.

PMID- 18091644
TI  - The role of intracardiac echocardiography in interventional electrophysiology.
AB  - Visualization of the cardiac anatomy becomes more and more important as the
      complexity of interventions increases. Intracardiac echocardiography (ICE)
      provides good depiction of cardiac soft tissue structures and has become an
      important tool in today's cardiology. It has been shown to be valuable during
      many ablation procedures for supraventricular and ventricular arrhythmias. ICE
      has been used for monitoring catheter placement, observing catheter-tissue
      contact and lesion formation as well as titrating ablation energy. The rate of
      complications could be reduced, outcome of procedures improved and radiation
      exposure decreased. Even more, new therapy strategies have been evaluated based
      on ICE and it has also been used in the setting of three- dimensional imaging and
      image integration.

PMID- 18091645
TI  - Techniques for transvenous leads extraction.
AB  - The number of implanted cardiac pacing and defibrillating devices is currently
      increasing, leading to an increasing number of device-related complications, due
      to either malfunction or infection. Removal of the whole system, including the
      leads, was proven to be the most effective therapy. At present the importance of
      transvenous lead extraction is consequently increased. In order to remove pacing
      and implantable cardioverter defibrillators (ICD) leads, they have to be made
      free from any binding site from the entry in the vein to the tip. Different
      techniques, including mechanical dilation, powered dilation and intravascular
      approaches have been developed over the last years and are currently available.
      Results reported in the literature show a significant success rate (ranging
      between 90% and 98% of the leads) and a reduced incidence of serious
      complications (1% to 3% in different series) in selected centres. The extraction
      procedures are complex and life-threatening complications may always occur,
      suggesting the need of trained and experienced operators as well as the
      availability of a surgical standby. At present indications to removal are
      restricted to infection or to damage of the leads inducing serious risk for the
      patients; the availability of a more effective and safe technique will probably
      spread indications to most of abandoned leads.

PMID- 18091646
TI  - A review of factors contributing to health related quality of life achieved with
      cardiac resynchronization therapy for heart failure.
AB  - Electrical cardiac resynchronization therapy (CRT) with biventricular pacing
      improves the impaired left ventricular function in selected patients and reduces
      mortality, morbidity and the number of hospitalizations for heart failure.
      Reversed left ventricular remodelling following CRT has been documented by
      various imaging METHODS: Application of CRT involves many factors as selection,
      implantation procedure, pacing site, programming of the atrioventricular and
      interventricular pacing intervals, optimal medical and anti-arrhythmic treatment
      and counselling of the patient with congestive heart failure (CHF). The
      contribution of various components of CRT to the hemodynamic response and to the
      left and right ventricular function has been extensively documented. Large
      prospective studies also demonstrated improvement of health related quality of
      life (QoL) compared to control patients. The cost-effectiveness of CRT and
      CRT/implantable cardioverter defibrillators (ICD) in terms of quality adjusted
      life year appears satisfying provided life expectancy of the recipient is
      enlarged. However, the follow up of most studies is rather short and QoL is
      always compared with the baseline condition. Furthermore, the clinical relevance
      of the reported numerical improvement of QoL and its persistence are fully
      unknown. The individual improvement of QoL of the CRT recipient cannot be
      predicted from clinical variables. Literature shows that the contribution of the
      various CRT factors to the hemodynamic response and to the left and right
      ventricular function and clinical benefit are extensively studied but not their
      contribution to health related QoL. For this purpose the contribution to QoL of
      all factors that are related to CRT response, was stepwise reviewed. Literature
      showed for several reasons no clear association with any individual CRT component
      and QoL. It can be concluded that prospective serial QoL studies of CRT patients
      in conjunction with studies of the cardiac function are requested to identify not
      only the contribution of CRT factors to QoL but also (sub)groups that benefit
      most. In these trials the methods and relevance of regular re-examination of the
      left ventricular function and of reprogramming of the device parameters to obtain
      a sustained positive CRT responsiveness, need to be established. Finally, because
      CRT has become a multidisciplinary therapy for chronic heart failure, the
      professional influence on QoL of the CRT recipient has to be studied.

PMID- 18091647
TI  - Pacemaker and implantable cardioverter defibrillator implantation in pediatric
      patients.
AB  - Pediatric pacing presents peculiar challenges and characteristics due to the
      peculiarity of children and adolescents, above all the somatic growth, but also
      the active lifestyle, the susceptibility to infections, and the generally
      anticipated long survival. In contrast, pacemaker (PM) generator and leads are
      designed for adult patients. Studies concerning children with PM are usually
      small, disomogeneous and without control groups. Large studies are rare.
      Moreover, concerns have been raised about long-term outcome of leads, ventricular
      and valvular dysfunction, venous patency, cosmetic results and psychological
      factors. So, it is still debated which systems have to be preferred, between the
      endocardial and the epicardial with steroid-eluting leads. Pediatric PM and
      (ICDs) show good results, but complications are still frequent, generally lead
      related, and often require reinterventions. As a general rule, less leads are
      implanted in children, less complications will occur in the future, and the
      simplest pacing system (generally, single-chamber PM) has better outcome. The
      creation of an atrial loop might allow the ''elongation'' of the lead with the
      growth. Endocardial and epicardial pacing with steroid-eluting leads have
      comparable electrical performances, expecially in absence of other congenital
      heart defects and previous heart surgery, although endocardial pacing shows the
      best outcomes: it should be the first choice in children over 10-15 kg.

PMID- 18091648
TI  - Vascular occlusion as a late complication of the Angio-Seal closure device. A
      review of literature.
AB  - Although early vascular complications of the Angio-Seal closure device have been
      well described, little is known about late vascular complications due to this
      device. The aim of this paper is to discuss late femoral stenosis associated with
      the use of the Angio-Seal closure device. A literature search was performed using
      Medline', Embase' and The Cochrane Library' to identify relevant articles
      published up to the first of May 2007. Late occlusion was defined as an occlusion
      after approximately one week after Angio-Seal deployment. All together, eleven
      relevant papers were available. The reported prevalence of late vascular stenosis
      associated with Angio-Seal use varies between 1/961 and 4/175. Claudication was
      the most frequently reported complaint. In most cases, late stenosis due to the
      use of the Angio-Seal required surgery. Vascular obstruction due to the device
      has been reported up to 6 months after placement. In conclusion, vascular
      stenosis due to the use an Angio-Seal closure device is a complication that not
      only occurs in the first few days after placement, but also in the following
      months. In every patient developing complaints of arterial insufficiency after
      using an Angio-Seal, local arterial stenosis due to the device should be
      considered in the differential diagnosis. It therefore is important to register
      the use of the device in the patient chart.

PMID- 18091649
TI  - Antibodies to oxidized low density lipoprotein: epidemiological studies and
      potential clinical applications in cardiovascular disease.
AB  - The pathogenesis of atherosclerosis is mediated by genetic susceptibility along
      with a variety of cardiovascular risk factors and environment influences. As
      atherosclerotic lesions progress, they manifest several features typical of
      chronic inflammation, such as the presence of monocyte/macrophages, T-cells and
      inflammatory cytokines. This inflammatory response is fueled and enhanced by
      oxidative stress, which may be the link between lipid disorders and inflammation.
      Oxidation of lipoproteins is intimately involved in all stages of atherosclerosis
      and oxidative byproducts co-localize with inflammatory cells. When low density
      lipoprotein enters the subintimal space, it is oxidized by several mechanisms,
      including both enzymatic and non-enzymatic pathways and becomes a ligand for
      scavenger receptors on macrophages leading to generation of foam cells. Oxidized
      LDL is not only pro-inflammatory and pro-atherogenic, but several of the
      neoepitopes generated during oxidation are highly immunogenic and result in the
      generation of autoantibodies. Autoantibodies to OxLDL are found within
      atherosclerotic lesions and in apparently healthy subjects, as well as patients
      with various manifestations of cardiovascular disease. In this article, the role
      of circulating autoantibodies to OxLDL in cardiovascular disease will be
      reviewed. Although controversy still exists, the overall evidence supports the
      notion that IgG autoantibodies to OxLDL are associated with pro-atherogenic
      properties and IgM autoantibodies to OxLDL with atheroprotective properties.
      Whether such antibodies have a modulating role or are merely reflectors of
      atherogenesis has not been fully determined. Data is also emerging on the role of
      natural antibodies, which are primarily of the IgM class, that recognize
      oxidation-specific epitopes. Among other properties, these antibodies may be
      involved in housekeeping functions in binding and clearing pro-inflammatory
      oxidized lipids and therefore may be atheroprotective. Several studies have also
      recently evaluated the potential therapeutic role of antibodies to OxLDL either
      through active immunization using OxLDL or model oxidation-specific epitopes as
      immunogens or through passive immunization with human antibodies directed to
      oxidation-specific epitopes. Although these investigation are at an early stage,
      they show promise that immune modulation may lead to novel approaches to treat
      atherosclerosis and cardiovascular disease.

PMID- 18091650
TI  - Accelerated in-stent restenosis after bare-metal stenting of a myocardial bridge
      and successful treatment with drug-eluting stenting.
AB  - Stenting of symptomatic myocardial bridges is a therapeutic option with
      documented good short-term outcome. However, limited data on the long term
      outcome of myocardial bridge stenting has shown a higher restenosis rate
      comparing to stenting of de novo atherosclerotic lesions. Drug-eluting stenting
      of de novo atherosclerotic lesions has reduced the rate of restenosis comparing
      to bare metal stenting, but there is no available data on drug-eluting myocardial
      bridge stenting. We present a case of accelerated in-stent restenosis after bare
      metal myocardial bridge stenting, successfully treated with drug-eluting
      stenting.

PMID- 18091651
TI  - Pre-hospital thrombolysis in Alta Irpinia: work in progress.

PMID- 18091652
TI  - Preoperative anaemia does not affect the early postoperative outcome in patients
      with lung cancer.
AB  - AIM: Several prognostic factors like age, gender, histology, stage, type of
      operation, associated disorders and administration of induction therapy have been
      evaluated to assess the risk of postoperative complications and outcome in
      patients with resectable lung cancer. Anemia is a frequent condition in this
      subset of patients being estimated up to 50%. The aim of this retrospective study
      was to evaluate the effect of preoperative anemia on early outcome after lung
      cancer resection. METHODS: One-hundred thirty nine consecutive patients
      undergoing surgery for non small cell lung cancer were retrospectively
      considered. The mean age was 64.8+/-11.6 years. No patient received blood
      transfusions or administration of erythropoetin preoperatively. Overall, we
      performed 96 lobectomies, 14 pneumonectomies, 2 bilobectomies and 27 atypical
      resections. A subset of 27 patients (19.4%) (group I) had a preoperative value of
      Hb less than 12 g/dl (10.4+/-1.9 g/dL). Seven patients of them were stage IA
      (26%), 9 stage IB (33.3%), 2 stage IIA (7.4%), 6 stage IIB (22.2%), 2 stage IIIA
      (7.4%) and 1 stage IIIB (3.7%). Age, gender, stage, type of operation, induction
      chemotherapy, comorbidities were evaluated by univariate analysis comparing
      patients with and without preoperative anaemia. The two groups were homogenous
      regarding demographic characteristics. RESULTS: Three patients (11.1%) in group I
      and 2 (1.8%) in group II required blood transfusions after surgery (P=0.01); 4 of
      them received pneumonectomy (P<0.0001). The overall morbidity was 17.9% (25/139);
      the most frequent complication was persistent air leakage, followed by retention
      of secretions. No statistically significant difference was observed between the 2
      groups about early mortality (1 patient-3.7% in group I and 2 patients-1.8% in
      group II) and postoperative complications (5 patients-18.5% in group I and 20
      patients-17.9% in group II). CONCLUSION: Preoperative anaemia is not a risk
      factor for an increased rate of postoperative complications and should not be
      considered a contraindication to surgery.

PMID- 18091653
TI  - Management of left sided colorectal emergencies. Results of a postal
      questionnaire.
AB  - AIM: Controversy continues over management of left sided colorectal emergencies.
      Historically, management was by a three-staged procedure but more recently a two
      staged procedure (Hartmann's) was adopted. Since Dudley's description of the
      safety of peroperative antegrade colonic irrigation and primary anastomosis (PA)
      in the 1980s, some surgeons have adopted this one staged procedure. Studies have
      reported good outcomes. However, uptake of a one-staged approach is by no means
      universal. The aim of this study was to establish the operative choices of
      surgeons for emergency left sided colonic pathologies. We also compared the
      operative choices of colorectal surgeons, with non-colorectal surgeons. METHODS:
      A paper questionnaire was sent out to 300 consultant surgeons, equally to
      colorectal and non-colorectal surgeons practising in UK. They were asked to state
      their specialist surgical interest and which operation they would perform for:
      obstructed sigmoid carcinoma; obstructed sigmoid colon due to diverticular
      stricture; perforated sigmoid carcinoma; diverticulitis and purulent peritonitis;
      perforated diverticulitis with faecal peritonitis. RESULTS: Of the 300
      questionnaires sent out 145 (48%) were returned. Of these 72 (50%) were
      colorectal surgeons, 58 (40%) were non colorectal surgeons. For obstructed
      sigmoid carcinoma, obstruction due to diverticular stricture and purulent
      diverticulitis, colorectal surgeons were statistically more likely to perform PA
      than non-colorectal surgeons. CONCLUSION: Our study indicates that colorectal
      surgeons are more likely to perform a single stage operation for all scenarios
      examined. It also shows that the attitude of surgeons in UK is changing and more
      are accepting the concept of specialistic management in complex colonic
      pathologies.

PMID- 18091654
TI  - Open Veress Assisted technique. Results in 2700 cases.
AB  - AIM: The risks of specific complications of the laparoscopic technique, caused by
      pneumoperitoneum and by insertion of the first trocar, although rare, are
      frequently reported in literature. METHODS: A retrospective study of the
      complications we had in the period from October 1998 to December 2006 was made on
      2700 patients who did not need any trocars in the umbilicus or with scars due to
      previous surgery, who were treated with a particular technique of
      pneumoperitoneum induction and the insertion of the first trocar, named ''Open
      Veress Assisted'' (OVA). RESULTS: We had two visceral complications (0,07%)
      (ileal perforations). CONCLUSION: Although no surgical technique is without
      risks, we believe that the use of our technique is safer than a blind insertion
      of the first trocar, especially among the patients with scars due to previous
      surgery.

PMID- 18091655
TI  - [Conservative approach for breast cancer. The experience of the European
      Institute of Oncology].
AB  - Conservative surgery represents the standard care for patients with early breast
      cancer. The aim of this review was to discuss the extension of conservative
      surgery in controversial fields such as after primary chemotherapy for large
      tumours or the possibility to repeat conservative surgery for a local
      reappearance. The project of a conservative approach to breast cancers continues
      with sentinel node biopsy which is worldwide performed more and more frequently.
      In our institute sentinel node biopsy is the standard procedure in the axillary
      staging of breast cancer even in those clinical scenarios which were previously
      considered either controversial or a contraindication such as in multicentric
      breast cancer, during pregnancy, in intra-ductal neoplasias, after primary
      chemotherapy, and male breast cancer. This conservative approach is completed by
      the possibility to deliver a partial breast irradiation and to provide patients
      with more personalized adjuvant treatments tailored on the biological features of
      the tumour.

PMID- 18091656
TI  - [Updated treatment of peritoneal carcinomas: a review].
AB  - Peritoneal surface malignancy (PSM) is a clinical entity with an unfavourable
      prognosis, which characterizes the evolution of neoplastic diseases from the
      abdominal and/or pelvic organs and could also be the terminal stage of extra
      abdominal tumors. Examples of diseases that can spread mainly within the
      peritoneal cavity are appendiceal tumors, ovarian cancer, colorectal cancer,
      abdominal sarcomatosis, gastric cancer and peritoneal mesothelioma. The
      locoregional therapy is defined as the combination of cytoreductive surgery (CRS)
      and intraperitoneal hyperthermic perfusion (IPHP). The rationale of this combined
      therapy for PSM is based on the natural history of this clinical entity that
      remains confined in the peritoneal cavity for most of its natural history. This
      pattern of spread would seem to indicate the potential usefulness of selectively
      increasing drug concentration in the tumour-bearing area by direct
      intraperitoneal chemotherapy instillation. This approach led to these outcomes:
      the median survival of colorectal carcinoma and ovarian cancer was 32 months;
      patients with peritoneal mesothelioma showed 57% survival at 5 years, while in
      patients with appendiceal mucinous tumors and pseudomyxoma peritonei (PMP) the 10
      years overall survival was 78%. A significant improvement in survival was
      associated with hyperthermic intra-peritoneal chemotherapy (HIPEC) in patients
      with gastric cancer. Considering the constant increasing of diseases treatable
      with this procedure, more centres should be activated. The establishment of a
      clear policy and scientific guidelines is mandatory, in order to perform the
      CRS+HIPEC safely, minimizing treatment-related morbidity and mortality and
      maximizing the results in terms of survival and quality of life.

PMID- 18091657
TI  - [Laparoscopic adhesiolysis in acute small bowel obstruction].
AB  - At the beginning of the laparoscopic surgery, intestinal obstruction was
      considered an absolute contraindication for this approach, because of the high
      risk of injuring the bowel. Today laparoscopic surgery for small bowel
      obstruction is still under evaluation. Adhesions are the most common cause of
      obstruction; although an important proportion of these patients can be
      nonoperatively treated, some of these require immediate operation. The aim of
      this review was to evaluate the reliability and immediate results of laparoscopic
      management of small bowel obstruction by postoperative adhesions. Laparoscopic
      management of acute small bowel obstruction is feasible, but it is often
      difficult and may be hazardous. The patients with acute obstruction may be
      undergo laparoscopy after a careful selection. Morbidity is low if the operation
      is performed by skilled. The immediate benefit is rapid intestinal motility and
      shorter hospital stay. The long-term effect is the prevention of small bowel
      obstruction recurrences by new postoperative adhesions.

PMID- 18091658
TI  - [Laparoscopic appendectomy].
AB  - Most laparoscopic procedures are performed on an elective basis. However, as
      general surgeons have gained more experience with laparoscopy, they are employing
      this procedure also for the evaluation and treatment of acute abdominal
      conditions such acute appendicitis, acute cholecystitis, perforated
      gastroduodenal ulcer and abdominal trauma, acute pancreatitis and intestinal
      obstruction. Although its advantages are still under debate, the laparoscopic
      approach has already been adopted by many centers in the emergency setting.

PMID- 18091659
TI  - [Spontaneous pneumoperitoneum: a case secondary to thoracic trauma].
AB  - Spontaneous pneumoperitoneum is the radiographic manifestation of free air in the
      peritoneal cavity without visceral perforations and peritoneal signs, and it
      occurs in about 10% of the cases of pneumoperitoneum. The etiology can be
      postoperative, thoracic, abdominal, gynecologic, idiopathic; it generally
      introduces a benign evolution and does not require surgical treatment but just a
      conservative approach. The authors describe here a case of spontaneous
      pneumoperitoneum secondary to thoracic trauma. This case is interesting for the
      occurrence of pneumoperitoneum without clinical peritoneal signs such as fever
      and leucocytosis, after closed thoracic trauma in absence of pneumothoracic and
      pneumomediastinum. Correct clinical approach has allowed a conservative treatment
      avoiding an useless laparotomy.

PMID- 18091660
TI  - Myocardial revascularization in porcelain aorta: impact of age on conduct of
      surgery.
AB  - Myocardial revascularization among patients with porcelain aorta is a real
      dilemma regarding bypass technique, choice of conduit and site of proximal
      anastomosis. The experience reported here is about two cases of patients (aged 28
      and 73 years) with porcelain aorta. Both patients had successful myocardial
      revascularization using beating heart technique. The younger patient had much
      more complicated surgical approach.

PMID- 18091662
TI  - Heart disease in Turner syndrome.
AB  - Turner syndrome (TS) is a relatively common disorder of female development caused
      by loss of all or part of one sex chromosome. Because short stature and premature
      ovarian failure are cardinal features of the syndrome, pediatric endocrinologists
      have taken the lead in care for these girls. Congenital cardiovascular disease
      affects approximately 50% of individuals and is the major cause of premature
      mortality in adults. Unfortunately, teenage girls are often lost to follow up
      after discharge from pediatric clinic. This review describes the spectrum of
      cardiovascular defects in TS with emphasis on identifying patients at risk for
      aortic dissection/rupture. Updated consensus guidelines for cardiac screening and
      care are reviewed and genetic pathways implicated in Turner cardiovascular
      disease, including premature coronary artery disease, are discussed. This
      material is of particular importance because cardiac care for adults with TS
      appears seriously deficient at present.

PMID- 18091661
TI  - Prevalence of celiac disease in patients with autoimmune thyroiditis.
AB  - AIM: Many autoimmune disorders are associated to celiac disease (CD) but the
      association with autoimmune thyroiditis has been more frequently documented; this
      is in part explained by a shared immunogenetic make-up, and in part caused to
      time gluten-exposition, as suggested by the significant correlation observed in
      celiac patients between the increase occurrence of autoimmune diseases and the
      length of exposure to gluten. The aim of this study was to establish the
      prevalence of celiac disease in a group of subjects with autoimmune thyroiditis
      newly diagnosed on the basis of antibodies anti-peroxidase (TPO). METHODS: A
      total of 113 untreated patients with TPO >70 IU/mL were enrolled. CD was screened
      by measuring anti-endomysial antibodies (EMA) both IgA and IgG; an high
      prevalence of positive serology was resulting in this group, justified, in part,
      from EMA IgG investigation. RESULTS: In fact 31/113 patients showed IgA and/or
      IgG positivity and were diagnosed as celiacs with jejunal biopsy. CONCLUSION: On
      the basis of this paper, such as in according to current research-setting
      studies, the greater frequency of CD in association to autoimmune thyroid disease
      suggests that all subjects with TPO should be routinely screened for CD, through
      EMA IgA and IgG. However, the performance of this screening has never been
      evaluated until now, even if it could, in fact, be valid in order to increment
      diagnosis of CD, today still undiagnosed.

PMID- 18091663
TI  - Cardiovascular risk in women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that has
      received an immense amount of attention in the recent years due to the possible
      associated risk of cardiovascular disease. Women with PCOS demonstrate an adverse
      cardiovascular profile characteristic of the cardiometabolic syndrome and an
      established risk of progression to type 2 diabetes. Despite the presence of
      cardiovascular risk factors and increased surrogate markers of cardiovascular
      disease, it is unclear if they develop accelerated atherosclerosis. This article
      summarized the recent development and findings of cardiovascular risk in women
      with PCOS, and finally the therapeutic options will be discussed.

PMID- 18091664
TI  - Evidence based medicine and effective interventions of pharmacological therapy
      for the prevention of osteoporotic fractures.
AB  - Osteoporosis and fractures associated with it constitute a real and serious socio
      medical problem, which only recently has come to the forefront of social
      consciousness. The authors are carrying out a critical re-examination of the
      medical literature of osteoporosis pharmacological treatment. Particular
      attention has been paid to studies which show a clear reduction of the primary
      endpoint that, in the case of this pathology, consists of a reduction of the
      fracturing event. According to the examination of the clinical studies
      introduced, antiresorptive bone agents, such as alendronate and risenderonate,
      turn out to be molecules with higher levels of evidence implicated on the
      reduction of the main osteoporotic fractures, in particular the reduction of
      vertebral and femoral fractures. The 10 years long-term extension studies, in
      particular those that have seen the employment of alendronate, found a positive
      outcome regarding densitometry data and a favorable trend in antifracture
      effectiveness. Ibandronate is another amino-bisphosphonate which was recently
      validated as an effective drug for the treatment of osteoporosis with its
      documented ability to meaningfully reduce vertebral fractures. Also ranelate of
      strontium, a drug that seems to explain its own result in a different way from
      the other antiresorptive bone agents, constitutes another valid alternative in
      the treatment of this pathology. Both of these molecules however, need further
      studies in order to estimate their antifracture effectiveness in the long term,
      particularly those related to femoral fractures. Teriparatide and the entire
      molecule paratohormone are usually not prescribed for its high cost in treatment
      and because, typically, patients with high-risk level fractures that are already
      affected, produce more vertebral fractures from moderate to severe intensity.

PMID- 18091665
TI  - Implant supported prostheses with Bone System implant system: a retrospective
      study with follow-up period up to 13-years about 1021 fixtures.
AB  - AIM: To analyze the data collected in 13 years of clinical controls in patients
      with oral rehabilitation on Bone System dental implant systems and to evaluate
      the success, failure and complications in daily implant dentistry, without strict
      inclusion criteria, in order to define the success or survival or failure of
      dental implants. METHODS: A total of 477 patients (231 men and 246 women)
      received dental implants for oral rehabilitation in 3 different private dental
      offices in Piedmont, Italy. A total of 1 021 fixtures were implanted from 1992 to
      2004; patients were followed up for a maximum of 13 years. Surgery was performed
      by the same operator using the same dental implant system (Bone System, Italy),
      with manufacturer modifications and improvements to the system as it evolved
      during the study period. Treatment planning and oral reconstruction on the
      inserted implants were carried out by 3 different specialists in prosthesis
      dentistry and 4 dental laboratory technicians. In the follow-up period, clinical
      success was defined as the degree of patient satisfaction and as the survival of
      restorations on dental implants. RESULTS: The survival rate of the fixtures was
      95.9%; the clinical effectiveness was 92.8%; the failure rate was 4.1%.
      Complications included peri-implantitis, implant fractures and technical
      complications related to implant components and prostheses. Long-term implant
      survival and clinical success were not influenced by anatomic site (maxilla or
      mandible). CONCLUSION: Dental implant therapy is a viable option for oral
      rehabilitation; if correctly managed, it may provide predictable results.

PMID- 18091666
TI  - Use of resorbable membranes in periodontal defects treatment after extraction of
      impacted mandibular third molars.
AB  - AIM: The aim of this study was to evaluate the efficacy of guided-tissue
      regeneration therapy (GTR) in the treatment of periodontal defects on the distal
      surface of mandibular second molars following surgical extraction of impacted
      third molars. METHODS: This split-mouth design study included 11 subjects who
      required extraction of bilateral impacted mandibular third molars and were at
      high risk for developing second molar periodontal defects after third molar
      extraction, that is mesioangular impaction and pre-existing periodontal defect
      (probing depth [PD] = or >5 mm) on the distal aspect of second molars. Within
      subjects, 1 postextraction site was randomly selected to receive scaling and root
      planing (SRP) of the distal surface of the second molar and the application of a
      polyglycolic acid/polylactic acid bioresorbable membrane (test site) and the
      opposite site served as control and was treated with SRP alone. The change in PD
      and clinical attachment level (CAL) as well as bone gain were assessed on the
      distal aspect of second molars over a 12-month period. RESULTS: Although both
      treatment modalities resulted in improvements in clinical parameters, the
      application of a bioresorbable membrane was statistical significantly more
      effective than SRP alone in reducing PD and in promoting CAL gain (P<0.0001). In
      10 GTR-treated sites a complete bone fill was achieved, while 10 out of 11
      control sites had residual intrabony defect. CONCLUSION: Subjects at high risk
      for developing second molar periodontal defects after third molar removal may
      benefit from the GTR-therapy at the time of surgical extraction of mesioangular
      impacted third molars to enhance periodontal healing.

PMID- 18091667
TI  - Influence of calcium hydroxide debris on the quality of endodontic apical seal.
AB  - AIM: The aim of the study was to study investigate the influence of calcium
      hydroxide used as intermediate medication on the quality of apical seal of a
      silicon based and an experimental resin based endodontic sealer. METHODS: Eighty
      endodontic canals were prepared and divided in four groups. Calcium hydroxide was
      applied in groups 2 and 4. After 7 days, medication was removed and canals were
      filled with gutta-percha and RoekoSeal Automix (groups 1 and 2) or Scotchbond
      MP+C&B cement B (groups 3 and 4). Specimens were placed into India ink, cleared
      and analyzed under a stereomicroscope to investigate apical leakage. RESULTS:
      Specimens that received calcium hydroxide medication showed leakage means higher
      than the corresponding untreated ones (i.e. group 1< group 2 and group 3< group
      4; P<0.001). CONCLUSIONS: Calcium hydroxide interferes with the sealing ability
      of silicon based sealer, since it frequently remains entrapped within the
      endodontic space even after careful removal procedures.

PMID- 18091668
TI  - Regenerative periodontal therapy in intrabony defects: state of the art.
AB  - Many scientific data show that periodontal regeneration is an effective and
      predictable procedure for the treatment of isolated and multiple intrabony
      defects. Meta-analyses from systematic reviews show a clinical advantage in terms
      of clinical attachment level gain when demineralized freeze dried bone allograft,
      barrier membranes and amelogenins are applied in comparison with open flap
      debridement alone. On the other hand, a consistent amount of variability of the
      outcomes is evident among different studies and within the experimental
      population of the same study. This variability is explained, at least in part, by
      the different patient and defect characteristics and by a different degree of
      skill of the surgeon. Patient-related factors are smoking habit, compliance with
      home oral hygiene and residual inflammation after cause-related therapy. Defect
      associated factors include defect depth and Rx angle, number of residual bony
      walls, pocket depth, and the degree of hypermobility. Surgical skill and
      experience to manipulate the delicate papilla preservation techniques is required
      along with the knowledge of indication and limits of the different regenerative
      materials. A strategy to optimise the surgical design of the flap, the use of the
      regenerative materials according to their characteristics, and the application of
      passive sutures is presented in this review, along with the foundation of the
      scientific background.

PMID- 18091669
TI  - Bone substitutes in oral surgery.
AB  - Osseous defects pose a clinical challenge the operator can meet with the aid of
      techniques that promote bone tissue regeneration. The current gold standard is
      autologous bone harvested from intra- and extraoral donor sites; however,
      autologous bone grafting requires two surgical sites (donor and recipient),
      resulting in greater morbidity and prolonged operating times, particularly for
      extraoral sites, with greater discomfort for the patient. Such disadvantages can
      be overcome with the use of bone substitute materials. There is a notable variety
      of so-called intelligent biomaterials that can modulate bone response in
      regeneration. Based on origin, bone substitute materials are classified as
      allogenic, heterologous and alloplastic materials. The first refer to bone from
      same-species donors, the second are obtained through processing of bone from
      different species, while alloplastic materials are synthetic composites. Besides
      different resorption rates, they possess different chemical and structural
      characteristics that influence the stimulation or support of bone regeneration.
      In daily clinical practice, before selecting from the wide variety of
      biomaterials, a wise step is to analyze and compare the clinical and histological
      results obtained with these materials. This article examines the clinical
      applications and osteoconductive and/or osteoinductive properties of some
      currently available biomaterials.

PMID- 18091670
TI  - Mild cognitive impairment.
AB  - A wide spectrum of cognitive ability is seen in older persons, ranging from
      intact cognitive function to clinically manifested dementia. The term mild
      cognitive impairment (MCI) is increasingly used to refer to individuals who have
      some cognitive impairment but do not meet the criteria for dementia. Despite a
      lack of consensus about precisely how to define MCI, researchers agree that the
      condition is relatively common in older people, and data suggest that MCI may be
      associated with an increased risk of Alzheimer's disease, parkinsonian signs and
      disability. Presently, the clinical assessment of MCI should include a detailed
      evaluation of cognitive functioning and the use of structural MRI can provide
      important diagnostic and prognostic information. Although therapeutic trials in
      MCI using the Choline acetylcholinesterase's have been disappointing with short
      term affects noted, pharmacologic prevention studies for MCI, are underway and
      may provide valuable data to prevent the development of this condition.

PMID- 18091671
TI  - Pathological correlates of cognitive decline in Alzheimer's disease.
AB  - Although Alzheimer's disease (AD) has been investigated for more than 100 years,
      it was not until the 60s that quantitative measures of the disease progression
      and severity in relation to function and neuropathology were made by Blessed and
      his colleagues. With the increasing understanding of the pathological changes of
      AD that take place, there is growing interest in identifying which pathological
      marker most reliably predicts the dementia and the cognitive profile. Markers of
      pathology that have been investigated include senile plaques, neurofibrillary
      tangles, synaptic loss, and neurochemical changes. Many clinical measures have
      been evaluated as well including Clinical Dementia Rating, Mini Mental State
      Examination, and Functional Assessment Staging as ways of both predicting the
      presence of pathological changes of AD as well as correlating with the specific
      measures of pathology. Accumulation of neuropathology appears to correlate with
      functional, global, and cognitive decline as people progress through AD. This
      review will summarize evidence of which neuropathological change correlates
      robustly with cognitive decline and which cognitive index predicts pathological
      changes in AD. In general, tangles and synaptic loss are better correlates of
      cognitive decline and correlate better.

PMID- 18091672
TI  - Vascular dementia: clinical, neuroradiologic and neuropathologic aspects.
AB  - Vascular dementia (VaD) is the second most common form of dementia after
      Alzheimer's disease (AD), and some studies suggest that the frequency increases
      exponentially over the age of 65 years. This review brings attention to the
      current challenges in the clinical and pathologic diagnoses of vascular dementia,
      provides an overview of diagnostic schemes in the clinical setting, and discusses
      the post-mortem pathology associated with VaD. While memory impairment is
      essential for diagnosis of AD, the clinical syndrome in VaD is often
      characterized by executive dysfunction rather than memory impairment.
      Nevertheless, the cognitive symptoms of VaD are so pleomorphic that no single
      cognitive syndrome captures the range of symptomology. Additionally, there are no
      widely accepted neuropathologic criteria for VaD. Imaging studies provide
      information about the distribution and volume of lesions and provide supportive
      information that differentiates VaD from AD, but are complicated by the concept
      of ''silent infarcts''. The heterogeneity of cerebrovascular disease and the wide
      range of pathologic lesions suggest that classification of VaD should include
      specific subtypes. The main challenge in clinicopathologic correlative studies is
      the lack of a gold standard for pathologic diagnosis of VaD that includes
      thresholds for number, size and location of infarcts and ischemic injury to white
      matter and strategic sites such as the thalamus and hippocampus. VaD is an entity
      that provides many challenges to the clinician, neuroradiologist and
      neuropathologist in part because evidence-based studies often lack clear
      definitions of the disease.

PMID- 18091673
TI  - Infective dementias.
AB  - A wide range of infectious diseases can result in dementia, although the identity
      and nature of these diseases has changed over time. Two of the most significant
      current groups in terms of scientific complexity are HIV/AIDS and prion diseases.
      In these disorders, dementia occurs either as a consequence of targeting the
      brain and selectively damaging neurones, or by an indirect effect of
      neuroinflammation. In prion diseases, both direct neurotoxicity and
      neuroinflammation may act to result in neuronal damage. In HIV encephalitis, the
      progression of the dementia is slower, perhaps reflecting indirect damage that
      appears to result from neuroinflammation as a main cause of neuronal death. An
      ever-increasing range of model systems is now available to study the neuronal
      damage in infectious dementias, ranging from cell culture systems to animal
      models, some of which, particularly in the case of prion diseases, are very well
      characterised and amenable to controlled manipulation in terms of both host and
      agent parameters. As valuable as these experimental models are, they do not allow
      a direct approach to an understanding of dementia, the complexities of which
      cannot readily be studied in vitro or in animal models, but they do allow studies
      of interventions and therapeutic strategies. This review summarises the current
      state of knowledge regarding the major infective dementias.

PMID- 18091674
TI  - Helicobacter pylori and dementia. Which consistency for an association?
AB  - Alongside gastroduodenal diseases, Helicobacter pylori (H. pylori) infection has
      been associated with extradigestive diseases, including dementia. To identify all
      publications on the association between H. pylori and dementia, a MEDLINE search
      of all studies published in English from 1965 to 2007 was carried on. Very few
      investigations were found. Furthermore, studies with sufficient powerful design
      did not exist; dementia as well as H. pylori infection were defined with a low
      degree of homogeneity, biases were obvious in the control groups, thus giving
      room for large variation in the adjustment of potential confounding factors.
      Future research should be focused on three main issues: 1) prospective population
      based studies, aiming to evaluate the consistency of epidemiological data with
      etiological hypotheses, and to provide the basis to develop and evaluate
      preventive procedures and public health practice; 2) intervention trials; 3)
      studies of physiopathology (both in the animal model and humans) to understand
      the potential biological plausibility of the association between H.pylori and
      dementia.

PMID- 18091675
TI  - Lower extremity kinematics and kinetics of Division III collegiate baseball and
      softball players while performing a modified pro-agility task.
AB  - AIM: Females experience at least twice as many non-contact anterior cruciate
      ligament (ACL) injuries as males. The aim of this study was to investigate if
      males and females exhibited different characteristics while performing a modified
      pro-agility test. METHODS: Collegiate Division III male baseball (n=14) and
      female softball (n=13) players performed 4 trials of a modified pro-agility task,
      which consisted of running toward a force platform target for 5 steps, planting
      their right foot, and propelling themselves off of the target with their left
      foot. Kinematic and kinetic parameters were compared using a multivariate
      analysis of variance between gender with the level of significance set at P<0.05.
      RESULTS: Males and females exhibited similar knee valgus angles. Females had a
      greater maximum knee extension angle (10.14 degrees vs 17.43 degrees ), and
      greater knee range of motion (46.12 degrees vs 40.12 degrees ). Both groups
      reached maximum knee flexion at 52% of stance. Females had significantly more
      maximum hip flexion than males (28.86 degrees vs 22.75 degrees ). Females had
      significantly smaller minimum internal knee varus moments than their male
      counterparts (1.12 Nm/kg vs 1.55 Nm/kg). Vertical ground reaction forces as a
      percentage of bodyweight, and stance time, were not statistically different. The
      female group displayed an external knee rotation angle (2.49 degrees ) during the
      beginning of their stance, which was significantly different than the internal
      rotation angle (4.11 degrees ) in the male group. Early in stance knee rotation
      angle was highly correlated with the lack of internal knee varus moment (males
      R(2)=0.75, females R(2)=0.88). CONCLUSION: Females displayed knee moments and
      kinematics that may place them at greater risk for ACL injury during a stop-cut
      task. Females should be coached to perform stop cuts with more knee flexion and a
      more neutral knee rotation angle upon foot contact in an effort to reduce moments
      that may place the ACL at risk.

PMID- 18091676
TI  - The relationship between isokinetic knee extension and flexion strength with
      soccer kick kinematics: an electromyographic evaluation.
AB  - AIM: The purpose of this study was to investigate the relationship between
      isokinetic strength knee testing and soccer kick kinematics using
      electromyography (EMG). METHODS: Thirteen pubertal soccer players (age: 14.3+/
      0.4 years) performed maximum instep soccer kicks, while knee angular position of
      the swinging leg was recorded using a twin-axis electrogoniometer. Bipolar
      surface EMG activity of the vastus medialis, vastus lateralis and biceps femoris
      (BF) muscles was recorded. The subjects also performed maximum knee extension and
      flexion efforts at concentric angular velocities of 1.04, 3.14 and 5.23 rad x s(
      1) and eccentric angular velocities of 1.04 and 3.14 rad x s(-1). RESULTS: The
      correlation coefficients between isokinetic moments and knee angular velocity
      values during the kick ranged from 0.609 to 0.898 for concentric moments and from
      0.431 to 0.612 for eccentric moments. Agonist EMG values during isokinetic tests
      ranged from 63.17+/-19.9% to 128.7+/-34.9% maximum voluntary contraction (MVC).
      Antagonist EMG levels ranged from 9.76+/-6.12% to 36.91+/-22.81% MVC. The
      corresponding EMG values during the soccer kick ranged from 12.78+/-6.8% to
      122.34+/-61.5% MVC and increased as the foot approached the ball. CONCLUSION:
      Isokinetic tests at intermediate and fast angular velocities are adequate for
      monitoring strength training programs in soccer. However, muscle activation
      patterns differ between the two movements, especially those of the BF muscle.

PMID- 18091677
TI  - Oxygen cost and energy expenditure of racquetball.
AB  - AIM: Many sports are played intermittently in bursts of high, moderate, and low
      intensity activity. The pattern of exercise intensity has been assessed from
      heart rate (HR) and time motion analysis and few data are available based on
      assessment of exercise intensity by means of direct measurement of oxygen uptake.
      The aim of this study was to directly assess oxygen uptake (VO(2)) using a
      portable metabolic measuring device to describe the aerobic demand and to
      determine the associated energy expenditure (EE). METHODS: Fourteen recreational
      racquetball players (3 females and 11 males; mean age, height, and mass of 23.1+/
      2.8 years, 178.1+/-7.1 cm, and 81.1+/-19.6 kg, respectively) played for 40 min
      while wearing a portable metabolic system to assess VO(2) and a Polar watch to
      measure HR. Rating of perceived exertion (RPE) (Borg 6-20 scale) was assessed at
      5 min intervals during breaks in play. RESULTS: The mean VO(2), HR, and RPE over
      40 min of play were 27.3+/-1.8 mL/kg/min, 155.3+/-2.8 bpm, and 12.9+/-0.6,
      respectively. The associated EE was a total of 1 844 kj (440 kcal) or 465 kj/min
      (11.1 kcal/min). These data were examined across 13.3 min time periods of play,
      in order to determine if they changed during play because of fatigue. VO(2)
      decreased significantly (P<0.05), while HR increased (P<0.05). RPE rose across
      periods of play, but not significantly. CONCLUSION: Recreational racquetball
      appears to elicit a VO(2) that would allow aerobic conditioning in many persons.
      It does so with an RPE that is nearly ''somewhat hard''.

PMID- 18091678
TI  - Relationship between measured maximal oxygen uptake and aerobic endurance
      performance with running repeated sprint ability in young elite soccer players.
AB  - AIM: The aim of the study was to determine the relationships between maximal
      oxygen uptake (VO(2max)) in a maximal treadmill run and the aerobic endurance
      performance in the 20-m multistage shuttle run (MST) test, with the performance
      indices obtained in the running repeated sprint ability (rRSA) test, in elite
      youth soccer players. METHODS: Thirty-seven adolescent male outfield players
      performed on separate days and in random order the treadmill run test and the
      MST, to obtain their measured VO(2max) and aerobic endurance performance (via the
      number of completed shuttles in the MST), respectively. Players also completed
      the rRSA test of 6x20-m all-out sprints, interspersed with 20 s of active
      recovery. RESULTS: There was a significant moderate correlation between measured
      VO(2max) (in L . min(-1) and mL . kg(-1) . min(-1)) and MST results (r=0.43 and
      0.54, P<0.05, respectively). There was no significant correlation between
      measured VO(2max) and aerobic endurance performance with any of the performance
      indices in the rRSA test (all P>0.05). CONCLUSION: The moderate association
      between the measured VO(2max) and MST suggests that both tests were plausibly
      measuring different aspects of a player's aerobic fitness. The lack of
      association between measured VO(2max) and aerobic endurance performance in the
      MST with performance in the rRSA suggests that aerobic fitness per se is poorly
      associated with performance in the rRSA in elite youth soccer players.

PMID- 18091679
TI  - Body cell mass measured by bioelectrical impedance spectroscopy in professional
      football (soccer) players.
AB  - AIM: The aim of this study was to measure body cell mass (BCM) in two football
      (soccer) teams and assess if there are differences in body composition among
      players of different field positions. METHODS: Two professional Italian (male)
      football teams, representing two different divisions (A and C), have been
      recruited. There were 14 players (4 forwards, 4 defenders, 6 midfielders) in A
      and 18 players (4 forwards, 4 defenders, 8 midfielders, 2 goalkeepers) in C. Fat
      free mass (FFM), fat mass (FM), percent body fat (%BF), and BCM have been
      assessed using bioelectrical impedance spectroscopy (BIS). RESULTS: There were no
      significant differences in age, body weight, height or body mass index between
      teams. Team A's BCM was approximately 4 kg greater than C (P=0.001). FFM was
      significantly greater in midfielders and defenders in A vs C (P=0.02). FFM was
      significantly lower in forwards compared to defenders within A (P=0.02). Within
      A, FM and %BF were significantly lower for defenders compared to forwards and
      midfielders (P=0.01), and BCM was significantly greater in forwards vs defenders
      (P=0.01), with no significant differences among other field positions. BCM was
      significantly greater in forwards vs midfielders and defenders within C (P=0.02),
      with no significant differences between midfielders and defenders. CONCLUSIONS:
      BCM, measured using BIS, represents an innovative, simple approach to assess body
      composition. The present study demonstrates that it is very important to analyze
      body composition in football players, not only with the aim to evaluate the
      variation of weight in a quantitative and qualitative way, but also with the
      purpose of selecting players for specific roles. Although these results must be
      considered not yet conclusive, they could be an important information for
      coaches, especially during the selection of young football players.

PMID- 18091680
TI  - Salivary cortisol, heart rate and blood lactate during a qualifying trial and an
      official race in motorcycling competition.
AB  - AIM: The study aims to examine the physiological load on motorcycling competitors
      during a qualifying trial and an official race. METHODS: Twelve male riders
      participated in this study, in which their anthropometric data, heart rate, blood
      lactate (La) and salivary cortisol (C) concentrations were measured. Two saliva
      samples were taken on a resting day at 8 a.m. (30 min after awakening: [T(0)] and
      at 8 p.m. [T(1)] and 6 saliva samples were collected on the day of the qualifying
      trial and on the day of the official race [T(2) through T(7)]). RESULTS: During
      the race, as well as during the qualifying trial, heart rate was found to be >80
      90% of the maximum heart rate. Blood La increased more than two-fold (peak 5.6+/
      2.1 mM) as compared to resting values (2+/-0.1 mM). However, La were not
      statistically different between qualifying trial and race. C concentrations on
      the motorcycling day were found to be up to 3 times higher than those measured on
      the resting day. In fact, there was a progressive increase in the C
      concentrations on the motorcycling day, the values noted 10 min after the race
      being the highest. There was a significant decrease in C values 60 min after the
      race, but the concentration was maintained at a higher level for a longer period;
      the values reported at T(7) (8 p.m.; 4.3 h after the end of the race) were
      significantly higher than those reported at the same time on a resting day
      (T(1)). CONCLUSION: The examination of heart rate, blood La and salivary C
      concentrations in motorcycling on a circuit shows that this sport is highly
      stressful, and also that a metabolic involvement is required to control the
      motorcycle at a high speed. Thus, riders may benefit from a specific training
      program aimed at improving their cardiovascular fitness and strength.

PMID- 18091681
TI  - Competition, estimated, and test maximum heart rate.
AB  - AIM: The aim of the present study was to compare the highest heart rate (HR) of
      soccer players recorded during competition matches with the maximum HR (HR(max))
      estimated from age and the highest HR recorded in effort tests within a single
      category (intracategory) and between categories (intercategories). METHODS: The
      sample was made up of 19 under-17 athletes, 12 under-20 athletes and 14
      professional athletes of a Brazilian first division soccer team. Players' HR was
      monitored during official competition matches and maximum effort test with a set
      of HR monitors. The highest HR recorded during competitive matches (MHR1) was
      considered as the highest HR value attained by each player during matches.
      HR(max) estimated from age (MHR2) was estimated by using the equation HR(max)=
      (220-age). The highest HR recorded in effort tests (MHR3) was determined as being
      the highest HR value recorded during a maximum effort test (1 000-m run). The
      Wilcoxon test was used in intracategory statistical analysis. The Kruskal Wallis
      test was used in intercategory statistical analysis. The significance level
      adopted was P<0.05. RESULTS: In all categories, MHR3 was lower than MHR1.
      Concerning intercategory analysis, the three categories did not exhibit a
      difference in MHR1 RESULTS: Relative to MHR3, the under-17 and under-20
      categories were not different from each other. These two categories exhibited
      larger MHR3 values than the professional one did. CONCLUSION: HR(max) measured
      during field tests can be underestimated in relation to that measured during
      competition activities, maybe because the tests represent an artificial situation
      for athletes, who do not feel as motivated as during competitions.

PMID- 18091682
TI  - Do aspartate and asparagine acute supplementation influence the onset of fatigue
      in intense exercise?
AB  - AIM: Oxaloacetic acid represents a fundamental intermediary in the metabolism of
      energy substrate. Asparagine and aspartate constitute precursor compounds of this
      substance. Therefore, they could affect tricarbossilic acids cycle. Besides, it
      was suggested that supplementation with aspartate and asparagine determines a
      muscular glycogen sparing during strenuous physical exercise, even if the real
      effectiveness remain controversial. The aim of the present pilot study was to
      evaluate the hypothesis that a supplementation with oxaloacetate precursors,
      precisely aspartate and asparagine, could improve sport performance during high
      intensity endurance exercise. METHODS: We recruited 15 male trained athletes,
      aged from 20 to 30 years (mean age: 24.13+/-3.87 years), practicing triathlon. We
      administered them placebo or aspartate (7 g) and asparagine (7 g) mixture, using
      a double blind technique, before performing an exhaustion stress test on
      cycloergometer carried out to 90% of each athlete's maximum oxygen consumption,
      previously determined. RESULTS: We evaluated lactatemia through earlobe punctures
      at the end of warming up, at the maximum effort and at recovery time (3 min, 5
      min, 10 min, 15 min, 30 min). Furthermore, subjects were submitted to three blood
      samples from brachial artery in order to assess the glycemia (before the
      exercise, at the end of the exercise, and 30 min after the end of the exercise).
      CONCLUSION: The analysis of these parameters and the results of the ergometric
      tests after amino acids assumption indicate that acute supplementation with
      aspartate and asparagine do not significantly affect physical performance in
      athletes practicing high intensity exercises, and that acute administration of
      aspartate does not cause a sparing of muscle glycogen concentration.

PMID- 18091683
TI  - An analysis of resistance training based on the maintenance of mechanical power.
AB  - Resistance training techniques, that increase the global power output of an
      exercise, exercise set and continuous sets, can optimize neuromuscular adaptation
      and dynamic athletic performance. An observation that is apparent during
      traditional resistance training is the slowing of movement velocity as fatigue
      increases. To perform at maximum velocity, only repetitions that permit
      maintenance of the maximum power output are essential for increasing the global
      power output. This article reviews the available research which examines the
      pattern of velocity decrease with different load intensities. In addition, an
      analysis is performed of the possible advantages of resistance training based on
      the maintenance of the mechanical power versus traditional resistance training.
      Furthermore, a variety of fact-finding lines are proposed with the objective of
      answering the numerous open questions related to resistance training based on the
      maintenance of mechanical power.

PMID- 18091684
TI  - Bone density gain at proximal phalanges in healthy males aged 18-25 years after
      16 weeks of upper-arm muscle weight training.
AB  - AIM: The aim of this study was to determine the effect of an upper-arm muscle
      weight training (WT) protocol over 16 weeks on bone density at the proximal
      phalanges in young healthy men. METHODS: Fifty-one healthy volunteer men were
      selected, 16 for an experimental group and 35 for a control group. The
      experimental group was submitted to the prescribed WT protocol to develop the
      strength of upper arm muscles, during 16 weeks, at a frequency of 3 times per
      week for approximately 60 min per session. Anthropometric data (weight, height,
      body mass index, corrected mid upper-arm circumference [cMUAC], and percentage of
      upper-arm muscle mass [%UAMM]) and bone density by quantitative ultrasound (DBM
      Sonic BP, IGEA, Italy) at proximal phalanges (amplitude dependent speed of sound
      [AD-SoS], T-score, %T-score) were evaluated on non-dominant limb before the
      beginning of the study (T0) and after 16 weeks (T1). RESULTS: There were no
      significant differences among all variables at T0 and T1 in the control group,
      nor at T0 between both groups. In the experimental group, cMUAC, %UAMM, AD-SoS, T
      score and %T-score were significantly higher at T1 in relation to T0, as well as
      between T1 of the experimental group and T1 of the control group (all with
      P<0.0001). The gain of %T-score showed a correlation between cMUAC gain (P=0.005)
      and %UAMM gain (P=0.002). The experimental group showed 7% of bone mass gain.
      CONCLUSION: These data suggested that a WT protocol to develop strength of upper
      arm muscles over 16 weeks was effective for increasing bone density at the
      proximal phalanges in healthy young men.

PMID- 18091685
TI  - Contraindications for whole body vibration training: a case of nephrolitiasis.
AB  - The use of whole body vibration (WBV) training is becoming more widespread both
      among athletes and the general public for improving muscle performance. The
      biological and mechanical effects of WBV are not completely understood and
      numerous contraindications, that can be identified while obtaining the patient's
      clinical history, must be taken into consideration. Nephrolithiasis, which often
      remains asymptomatic for an indefinite time, is not reported in the medical
      literature as a contraindication to WBV. This paper reports a case of significant
      morbidity following one session of WBV training in a patient with asymptomatic
      nephroli-thiasis.

PMID- 18091686
TI  - Factors associated with anterior cruciate ligament injury: history in female
      athletes.
AB  - AIM: Little is known about the association of lower extremity structural
      malalignments, flexibility patterns, generalized laxity, postural control,
      previous ankle sprain history and the increased risk of anterior cruciate
      ligament (ACL) injuries in females. We hypothesized that females with a history
      of ACL injury would be more likely to have a history of prior ankle sprain and
      different structural alignments than females without a history of ACL injury.
      METHODS: It is a case control study: 33 young adult females with a history of an
      ACL injury and 33 controls with no history of knee injury provided their knee and
      ankle injury history and had 16 lower extremity measures taken. RESULTS: The
      factors most associated with ACL injury history were greater generalized laxity
      (r(2) change: 0.073), greater genu recurvatum (r(2) change: 0.069), and decreased
      iliotibial band (ITB) flexibility (r(2) change: 0.069). There was also a
      significant association between ACL injury history and previous ankle sprain
      injury history (chi squared=5.27; P=0.02). Those with a history of ACL injury
      were more likely to have had a prior ipsilateral ankle sprain. CONCLUSION:
      Increased generalized laxity, greater genu recurvatum, and decreased ITB
      flexibility discriminated between females with and without history of ACL injury.
      A relationship linking previous ankle injury and ACL injury risk was found.
      Taking a thorough medical history and screening for generalized laxity, genu
      recurvatum, and a tight ITB in those with a history of LAS, may help identify
      those at risk for an ACL injury and who may benefit most from preventive
      measures.

PMID- 18091687
TI  - Predictors of moderate and severe injuries in Italian major leagues soccer teams:
      results from a cohort study.
AB  - AIM: The possible consequences of injury in soccer players could be a relevant
      public health issue, due the large diffusion of this sport around the world. We
      have evaluated the predictive value of both personal and professional
      characteristics on the occurrence of injuries and their severity in a prospective
      cohort study. METHODS: A cohort of 1 041 professional soccer players from the two
      Italian major Leagues was assembled during the season 2003-2004: 743 out of 785
      subjects available the day of the interview (94.6%) answered an epidemiological
      questionnaire. A validation study was performed to assess if participating
      subjects were representative of the whole cohort. The risk of injuries and their
      severity according to several variables were assessed. RESULTS: A total of 157
      subjects suffered 177 injuries during the season 2002-2003. Differences exist
      between injured and non-injured players according to both the number of matches
      played during the season and the League. A trend in risk of injury with
      anthropometric measures was observed, although not significant. The type of
      tissue and the type of injury were significantly associated with the duration of
      the stop. CONCLUSION: Anthropometric measures and career history (such as type of
      League and number of played matches) could require further attention, since they
      seem to be predictive of injury occurrence in soccer players.

PMID- 18091688
TI  - Association between sleep quality and physical fitness in female young adults.
AB  - AIM: Sleep quality and physical fitness are critical for young adults' growth and
      health. However, no study has examined the association between sleep quality and
      physical fitness in young adults. METHODS: A total of 291 female college students
      (mean age: 19.3+/-0.6 years; mean height: 160.3+/-5.2 cm; mean weight: 52.2+/-9.8
      kg), in the northern part of Taiwan, volunteered as subjects. For sleep quality
      evaluation, a valid Chinese version of the Pittsburgh Sleep Quality Index (PSQI)
      was used. For physical fitness testing, a battery of field-based health-related
      fitness tests was conducted by well-trained instructors. Data was analyzed using
      independent t-tests and the Pearson product-moment correlation coefficient.
      RESULTS: Subjects with poor sleep quality (P) (PSQI score >5) were more likely to
      have lower levels of muscular endurance, flexibility, and cardiovascular fitness.
      Significant correlations were also found between the global PSQI score and
      physical fitness performances in female young adults. CONCLUSION: This study
      confirmed the high prevalence of P among young adults. Education materials should
      try to prevent young adults from developing poor sleep patterns and inactive
      lifestyles. Moreover, subjects with P should take better care of health problems
      from cardiovascular disease and musculoskeletal injury.

PMID- 18091689
TI  - Influence of a medium-impact aquaerobic program on health-related quality of life
      and fitness level in healthy adult females.
AB  - AIM: The aim of the study was to examine the influence of a medium-impact
      aquaerobic program on the health-related quality of life (HRQoL) and health
      related fitness (HRF) level of middle-aged healthy female subjects. METHODS:
      Twenty apparently healthy women (mean age: 43.1 [standard deviation: 9.7] years)
      participated in the study. Criteria for inclusion were absence of diagnosed
      illnesses, as well and signs and symptoms of disease as evaluated by the Physical
      Activity Readiness Questionnaire. Participants carried out a medium-impact
      aquaerobic exercise program consisting of 2 weekly sessions of 60 min during 8
      months. Before and after the exercise program, HRQoL was assessed by the 36-item
      short form health survey (SF-36) questionnaire, and HRF was measured using a
      simplified version of the AFISAL-INEFC HRF test battery. RESULTS: Following the
      exercise program, an increase in all domains of HRQoL, except general health and
      role-emotional, was observed. Total body mass and body fat percentage decreased,
      and estimated aerobic power increased. CONCLUSION: Completion of a medium-impact
      aquaerobic program (2 weekly sessions of 60 min during 8 months) improves HRQoL
      in most domains, particularly bodily pain and vitality, and shows to be among the
      most effective programs for improving perceived quality of life. Moreover, this
      exercise program proved to have a positive influence on the body composition and
      functional capacity of the subjects, being effective in reducing fat body mass
      and improving cardiorespiratory function.

PMID- 18091690
TI  - A prospective study of the relationships of autonomy, competence, and relatedness
      with exercise attendance, adherence, and dropout.
AB  - AIM: Given the need to investigate determinants of exercise behavior, the study
      examined the relationship of the needs for autonomy, competence, and relatedness
      with exercise attendance and adherence/dropout in organized exercise programs
      over 6 months. A secondary purpose was to further determine the predictive
      validity of the Basic Psychological Needs in Exercise Scale (BPNES) responses.
      METHODS: A prospective design was utilized where 108 male exercise participants
      (mean age: 27.38 years) and 120 females (mean age: 27.79 years) completed the
      BPNES before an exercise class. Six months later, the total number of their
      visits to the fitness center over the 6-month period was assessed, as well as
      whether they still attended. RESULTS: Latent variable structural equation
      modeling demonstrated that it was only the need for competence that significantly
      predicted exercise attendance and this was the case for both male and female
      participants, simultaneously. Further, a binary logistic regression demonstrated
      that only the need for competence predicted group membership among participants
      who were categorized either as adherers or dropouts. CONCLUSION: The need for
      competence emerged as the main predictor of levels of exercise attendance and of
      exercise adherence/dropout group membership. Moreover, the findings further
      supported and broadened the validity evidence base of the BPNES responses.

PMID- 18091691
TI  - Short duration exhaustive aerobic exercise induces oxidative stress: a novel play
      oriented volitional fatigue test.
AB  - AIM: Exercise is associated with the generation of reactive oxygen and nitrogen
      species. This study examined the oxidative stress in response to a novel
      volitional fatigue test. METHODS: Eleven male college students performed a
      volitional fatigue test consisting of shuttle runs with a tennis racquet in the
      hand towards the left and right sidelines within the tennis singles court in an
      attempt to hit tennis balls until exhaustion. A tennis ball serving machine was
      adjusted to alternate feeds to the forehand and backhand sides of the subjects,
      standing at the baseline, at a frequency of 20 balls per minute. RESULTS: Mean
      time to volitional fatigue was 5.9+/-1.3 min and mean heart rate at volitional
      fatigue was 189+/-8.1 beats x min(-1). The volitional fatigue test resulted in
      significant increases in blood thiobarbituric acid-reactive substances (22%),
      protein carbonyls (58%), catalase activity (143%), total antioxidant capacity
      (34%) and oxidized glutathione (GSSG, 81%) concentration, as well as significant
      decreases in reduced glutathione (GSH, 15%) concentration and GSH/GSSG ratio
      (56%) immediately postexercise, as compared to the pre-exercise concentration.
      CONCLUSION: The data provide evidence that acute short duration exhaustive
      aerobic exercise in the form of a novel volitional fatigue test is capable of
      inducing oxidative stress. This novel test could serve as an alternative exercise
      modality to study oxidative stress.

PMID- 18091692
TI  - Ketone production in ultra marathon runners.
AB  - AIM: The aim of this study was to determine the magnitude of ketone production in
      ultra marathon runners and what affect if any this has on performance. METHODS:
      Participants in the Cliff Young Australian Six Day Race (n=31) provided a prerace
      urine sample and, then, random urine samples throughout the duration of the
      event, ranging from 4-20 samples each. Based on urinalysis results, participants
      were divided into two groups: those who formed ketones (ketone group), and those
      who did not form ketones or formed ketones only once during a race at the lowest
      recordable value (non-ketone group). RESULTS: The average ketone level of the 22
      athletes in the ketone group (value+/-standard deviation: 5.67+/-5.59 mg/dL) was
      statistically different from 9 athletes who were in the non-ketone group (0.18+/
      0.14 mg/dL) (P<0.05). The average distances run for the two groups were 498.09+/
      153.99 and 535.6+/-181.08 km, respectively (P=0.56). When average ketone value
      was compared, excluding runners who did not complete the race, the ketone group
      (5.88+/-1.37) remained statistically different from the non-ketone group (0.2+/
      0.45) (P<0.05). The average distances for those athletes who completed the race
      were 583.9+/-116.09 and 557.8+/-85.82 km, respectively (P=0.52). CONCLUSION: We
      conclude that although two runner sub-populations were revealed, runners who
      produce ketones and runners who do not make ketones, the level of ketones
      produced did not affect overall distance run, which is the performance criterion
      of the race. The nature of this extreme event has illuminated a physiologic
      difference among ultra marathon runners, and although this difference does not
      appear to affect race performance, the long-term health consequences are unknown
      and additional rigorous research is warranted.

PMID- 18091693
TI  - The effect of an ultra-endurance running race on mucosal and humoral immune
      function.
AB  - AIM: There are reports of the effect of endurance exercise on mucosal immune
      function and of the effect of short duration exercise on humoral immune function.
      However, little is known of the effect of endurance exercise on humoral immune
      function and the related risk of infection. This study examined the effects of an
      ultra-endurance running race on salivary immunoglobulin-A (s-IgA), serum IgA,
      leukocyte subset concentrations and the incidence of upper respiratory tract
      infections (URTI). METHODS: Thirteen male and 4 female competitors provided
      saliva samples and blood before and at several times after the running race. Self
      reported symptoms of URTI were also recorded for 2 weeks before and 2 weeks after
      the race. RESULTS: Salivary IgA secretion rate (P=0.005) and ratio to osmolality
      (P=0.006) were lower immediately postrace and decreased further for at least 2
      more h. s-IgA secretion rate had not returned to normal the next morning
      (P=0.009). Serum IgA concentration was lower post- than prerace (P=0.003) and was
      even lower the next morning (P<0.001). Leukocyte concentration was elevated
      postrace (P<0.001), mainly because of an increase in neutrophils (P<0.001) and
      both remained high the morning after the race (P<0.001). Lymphocyte concentration
      decreased postrace (P<0.001) and was still depressed the next morning (P=0.032).
      The incidence of symptoms of URTI was the same in the two 2-week periods before
      and after the race. CONCLUSION: These findings support the hypotheses that an
      ultra-endurance run may adversely affect mucosal immunity and cause significant
      changes in the concentration of leukocyte subsets.

PMID- 18091694
TI  - Severe rhabdomyolysis after excessive bodybuilding.
AB  - A 46-year-old male subject performed excessive physical exertion during 4-6 h in
      a studio for body builders during 5 days. He was not practicing sport prior to
      this training and denied the use of any aiding substances. Despite muscle aching
      already after 1 day, he continued the exercises. After the last day, he
      recognized tiredness and cessation of urine production. Two days after
      discontinuation of the training, a Herpes simplex infection occurred. Because of
      acute renal failure, he required hemodialysis. There were absent tendon reflexes
      and creatine kinase (CK) values up to 208 274 U/L (normal: <170 U/L). After 2
      weeks, CK had almost normalized and, after 4 weeks, hemodialysis was
      discontinued. Excessive muscle training may result in severe, hemodialysis
      dependent rhabdomyolysis. Triggering factors may be prior low fitness level,
      viral infection, or subclinical metabolic myopathy.

PMID- 18091696
TI  - Management of deep vein thrombosis.

PMID- 18091697
TI  - The role of inflammation in venous thromboembolism and the link between arterial
      and venous thrombosis.
AB  - During the last decade, the role of inflammation in the etiopathogenesis of
      arterial thrombosis has been elucidated. However, little is known about the
      relationship between inflammation and venous thrombosis. Recently, inflammation
      has been accepted as a possible mechanism through which different risk factors
      trigger thrombus formation in veins. The data indicate that inflammation of the
      vessel wall initiates thrombus formation in an intact vein and that inflammation
      and coagulation systems are coupled by a common activation pathway. The first
      event in thrombus formation is most probably activation of endothelial cells,
      platelets and leucocytes, with initiation of inflammation and formation of
      microparticles that trigger the coagulation system through the induction of a
      tissue factor. Therefore, the key event in the initiation of venous thrombus
      formation is most probably vein wall inflammation. However, expected relationship
      between inflammatory markers as indicators of inflammatory process and clinical
      venous thromboembolism (VTE) has not yet been elucidated. C-reactive protein does
      not appear to be useful in predicting future venous thrombosis or to be useful in
      the diagnosis of VTE. Recently, it was demonstrated that probable association
      between VTE and several other markers of inflammation such as: interleukin (IL)
      6, IL-8 and tumor necrosis factor-a exists. While these markers of inflammation
      were studied during or after acute venous thrombosis, further prospective studies
      are needed to determine the predictive value of inflammatory markers for VTE. The
      identification and elucidation of inflammatory markers relevant to venous
      thrombosis could provide targets for future therapy. That inflammation is the
      basic etiopathogenetic process of VTE is also supported by the relation of some
      risk factors to both arterial and venous thrombosis: age, increased body mass
      index, hypercholesterolemia, hypertension, lupus anticoagulant and
      hyperhomocysteinemia. A relation was also found between preclinical and clinical
      atherosclerotic disease and VTE. Also in line with these arguments are the
      preventive effects of aspirin and statins in both arterial and venous disease.

PMID- 18091698
TI  - Markers of inflammation and prevalence of vascular disease in patients with
      metabolic syndrome.
AB  - AIM: The aim of this study was to determine the prevalence of carotid
      atherosclerosis and coronary heart disease and cerebrovascular disease in
      subjects with metabolic syndrome and to investigate the relationship between
      atherosclerosis and C-reactive protein (CRP) levels. METHODS: We studied 568
      ambulatory subjects, referred to our Center for the study of atherosclerosis and
      cardiovascular prevention by general practitioner, for the presence of
      traditional cardiovascular risk factors. Subjects were divided in two groups:
      those with metabolic syndrome (n=163), and those with 0-2 metabolic abnormalities
      (n=405). All subjects underwent carotid artery ultrasound and blood tests
      including high sensitivity-CRP measurement. RESULTS: Prevalence of carotid
      lesions, previous cardiac or cerebrovascular events was higher in patients with
      metabolic syndrome. CRP levels were higher in patients with metabolic syndrome
      (0.6+/-0.23 vs 0.42+/-0.2, P<0.01). An increased relative risk for carotid
      atherosclerosis, coronary heart disease and cerebrovascular disease was not
      associated with each single component of the metabolic syndrome, but it was
      significantly associated with the coexistence of three or more of these. Patients
      with the metabolic syndrome had a higher incidence of carotid and coronary
      disease, if CRP levels were above 0.3 mg/dL. CONCLUSION: Patients with metabolic
      syndrome are at increased risk for cardiovascular events. Strategy to treat these
      patients is not well clarified. Life style changes are mandatory, but in very
      high-risk subgroups secondary prevention strategies may be advisable. These may
      be identified by using CRP levels as a marker.

PMID- 18091699
TI  - Association between inflammatory markers and the interleukin-6 -174 G/C
      polymorphism is abolished in peripheral arterial occlusive disease.
AB  - AIM: The interleukin-6 (IL-6) -174 G/C polymorphism has been reported to
      determine IL-6 levels and contribute to the development of cardiovascular
      disorders. The aim of our study was to evaluate the effect of the IL-6 -174 G/C
      polymorphism on hemostatic or inflammatory markers in patients with peripheral
      arterial occlusive disease (PAOD), a common manifestation of obliterative
      atherosclerosis. METHODS: Plasma IL-6, fibrinogen, C-reactive protein (CRP),
      tissue plasminogen activator, plasminogen activator inhibitor-1 (PAI-1),
      fibrinopeptide A and intercellular adhesion molecule-1 levels were determined in
      PAOD patients (n=50) and healthy controls (n=30) genotyped for the IL-6 -174 G/C
      polymorphism. RESULTS: In the control group, IL-6, CRP and fibrinogen levels were
      significantly associated with the IL-6 -174 G/C polymorphism with a gene-dosage
      effect being the highest in the CC subjects and the lowest in those with the GG
      genotype (P<0.0001, P=0.0002 and P=0.0001, respectively). Interestingly, the CC
      homozygotes had lower PAI-1 levels than carriers of the G allele (P=0.04). In
      PAOD patients, the IL-6 -174 G/C polymorphism had no effect on all the variables
      measured. CONCLUSION: In contrast to apparently healthy subjects, the IL-6 -174
      G/C polymorphism showed no association with plasma IL-6, CRP, fibrinogen and PAI
      1 levels in PAOD patients.

PMID- 18091700
TI  - Percutaneous transluminal angioplasty of the subclavian arteries.
AB  - AIM: The aim of this study was to review the feasibility, safety and long-term
      results of subclavian artery (SA) angioplasty. METHODS: Over 14 years, 237
      patients (males: 135; mean age: 64+/-12 years) underwent percutaneous treatment
      for SA occlusive disease. Indications for treatment were upper limb ischemia
      (n=125), vertebrobasilar insufficiency (n=128), coronary steal (n=11) and
      anticipated coronary bypass surgery in asymptomatic patients (n=26). A total of
      192 arteries were stenosed and 45 occluded. Mean percentage stenosis was 81.9+/
      7.6% and mean lesion length was 23.8+/-8.8 mm. Percutaneous techniques included
      retrograde femoral (n=163), brachial artery (n=47) access or both (n=14) and in 4
      cases the ''pull through technique''. An isolated balloon angioplasty was
      performed in 59 cases. We implanted 132 balloon expandable stents and 32 self
      expandable stents. RESULTS: Technical success was obtained in 223 lesions (94%).
      Only 31 occlusions were recanalized (69%). Four periprocedural events occurred
      (1.2%), 1 major (fatal) stroke, 1 transient ischemic attack and 2 arterial
      thromboses. At follow-up (mean follow-up: 65.8+/-33.5 months), we had 27
      restenoses (12%). Thirteen occurred following angioplasty alone (18.8%) and 14
      following angioplasty and stent implantation (8.4%). Primary (PI) and secondary
      (PII) patencies on an intention to treat basis at 10-year follow-up were 78.1%
      and 84.5%, respectively. In patients without initial stent placement, the rates
      were 67.5% and 75.5%, while in those with stents the rates rose to 89.7% and
      96.9% (P<0.01). PI for all recanalized lesions were 84.6%, 79.1% without stent,
      89.7% with stent (P<0.04) and PII 91.6%, 88.5%, 96.9%, respectively (P<0.02).
      CONCLUSION: Percutaneous transluminal angioplasty is currently the treatment of
      choice for SA lesions. It is a safe and effective procedure associated with low
      risks and good long-term results. Stents seem to limit the restenosis rate and
      improve long-term results.

PMID- 18091701
TI  - The importance of ceruloplasmin oxidase activity in patients with chronic lower
      limb atherosclerotic ischemia.
AB  - AIM: Inflammatory reactions accompanying ischemia increase the cytokine synthesis
      what leads to the increase in serum ceruloplasmin (Cp) concentration and
      activity. The aim of the study was to evaluate the association between serum Cp
      oxidase concentration and activity and the grade of lower extremity ischemia.
      Moreover, the correlation of Cp concentration and activity with the levels of
      interleukin 6 (IL-6), C-reacting protein (CRP), and a-1-acid glycoprotein (AGP)
      in serum was studied. METHODS: Two groups of patients were examined: 15 patients
      with moderate (MI) and 32 patients with critical ischemia (CI) of the lower
      extremities. Cp oxidase activity was measured spectrophotometrically, after
      incubation with o-dianisidine. The concentration of IL-6 was measured with the
      ELISA method, and Cp, CRP and AGP concentration by rocket immunoelectrophoresis.
      RESULTS: Significant increase in Cp oxidase concentration and activity was
      observed in patients with critical limb ischemia (median: 164.8 U/L), especially
      in patients with necrotic changes (median: 216.6 U/L). Cp oxidase activity was
      dependent on its concentration in patients with critical limb ischemia with
      necrotic changes (r=0.56; P<0.01). In patients with critical limb ischemia, the
      increase in Cp concentration and activity correlated significantly with CRP
      concentration (r=0.46; P=0.0007) (r=0.62; P=0.0001), respectively. CONCLUSION:
      Concentration and the oxidase activity of Cp depend of the degree of lower
      extremity ischemia and correlates with the major markers of inflammation, such as
      CRP. Critical limb ischemia induces the inflammatory reaction triggering the
      increase in IL-6 and of acute phase protein production. These processes lead to
      the increase in Cp oxidase activity dependent of Cp and CRP concentration.

PMID- 18091702
TI  - Extracoronary atherosclerosis in patients with chronic ischemic heart disease:
      relationship with risk factors and the severity of coronary artery disease.
AB  - AIM: The aim of the present study was to investigate the prevalence of carotid
      and/or peripheral atherosclerotic lesions in patients with chronic ischemic heart
      disease (previous acute myocardial infarction [AMI] or stable angina). METHODS:
      We studied 248 patients (168 male and 80 female), mean age 63+/-10 years, which
      were investigated for traditional risk factors. Systolic blood pressure, body
      mass index, lipid profile, fasting glucose and plasma fibrinogen were also
      measured. We assessed the prevalence of atherosclerotic lesions in carotid and
      lower limb arteries, by ultrasound duplex scanning (UDS). RESULTS: Angina was
      present in 33% of the patients, a previous AMI in 67%, a previous transient
      ischemic attack in 4% and a previous ischemic stroke in 6% of patients. A total
      of 195 patients underwent coronary angiography: 1 vessel was involved in 48% of
      patients, 2 vessels in 33%, and 3 vessels in 19%. Detecting peripheral
      atherosclerotic lesions by UDS, increased intima-media thickness (IMT) or plaques
      in carotid arteries were found in 232 patients (94%) and carotid stenosis >70% in
      13 patients (5%). In lower limb arteries, IMT or plaques were present in 202
      patients (82%) and a stenosis >70% in 18 patients (7%). Severity of coronary
      artery disease (CAD) was correlated to extracoronary atherosclerosis: carotid and
      lower limb arterial atherosclerosis was detected in 73% of patients with 1
      vessel, in 83% of patients with 2 vessel, in 87% of those with 3 vessel CAD.
      CONCLUSION: Our study suggests that in patients with CAD, it is useful to screen
      the peripheral circulation by non-invasive tests, such as UDS. Patients with the
      diagnosis of ischemic heart disease and combined extracoronary atherosclerosis
      need a careful follow-up and a more aggressive therapy for secondary prevention.

PMID- 18091703
TI  - Carotid artery disease in octogenarians: endarterectomy or stenting?
AB  - AIM: Carotid endarterectomy (CEA) is the gold standard for the treatment of
      carotid stenosis, but carotid angioplasty and stenting (CAS) has emerged as a
      potential less invasive therapeutic alternative to patients who would otherwise
      be considered as high risk for open surgery. The aim of this review was to pool
      the most current studies of the growing body of literature in which outcomes of
      CEA or CAS are compared in octogenarians and non-octogenarians to determine the
      current safety and efficacy of these therapeutic procedures, due to a lack of
      randomized controlled trials. METHODS: An electronic search of Medline, PubMed
      and Cochrane databases was supplemented by a review of bibliographies of relevant
      articles, as well as manual searches of relevant journals. Outcomes included 30
      day stroke rate, death rate, combined stroke/death rate and myocardial infarction
      rate between octogenarians and non-octogenarians. RESULTS: Randomized clinical
      trials or studies comparing CEA and CAS in the same study population were not
      identified. CEA and CAS outcomes, in octogenarians compared to younger cohorts,
      were evaluated in 10 and 5 studies, respectively. Analysis of data indicates no
      significant difference in adverse events reported in the two groups in the
      majority of studies of CEA, as opposed to the findings of CAS studies.
      CONCLUSION: The current review supports the viewpoint that CEA remains the
      standard of care in octogenarians, towards which other procedures to prevent
      stroke should be compared. It also challenges the definition of the ''high
      risk''/age blanket classification and suggests that until the longevity, safety
      and efficacy of CAS is established, wide applicability of CAS to such ''high
      risk'' patients should be questioned and limited to ongoing controlled clinical
      trials.

PMID- 18091704
TI  - European continuing medical education in vascular surgery: 5-year results of
      congresses approved by the Union Europeenne des Medecins Specialistes Section of
      Vascular Surgery.
AB  - AIM: Continuing medical education (CME) can be defined as ''educational
      activities that serve to maintain, develop, or increase the knowledge, skills and
      professional performance of a physician to provide services for patients, the
      public, or the profession''. CME is a major professional responsibility. The
      European Board of Vascular Surgery of the Union Europeenne des Medecins
      Specialistes (UEMS) Section of Vascular Surgery has, through its European
      Vascular CME (EVCME) Committee, accredited 74 congresses during the 5-year period
      from 2000-2004. METHODS: Official evaluation forms were completed by the congress
      participants for a personal appraisal of the quality of the activities. The data
      in this manuscript focused on questions that were the most relevant and of the
      greatest interest to the participants. A statistical analysis of the results was
      performed utilizing ANOVA and Robust tests of equality of means as well as a
      posthoc analysis for further investigation, and non parametric Wilcoxon signed
      ranks test. RESULTS: The educational needs of participants regarding new
      diagnostic and therapeutic modes were stated as ''important'' and ''extremely
      important'' in the responses at over 80% in total. Over 75% of the participants
      answered ''extremely important'' and ''important'' to the question ''how
      important is evidence-based practice to your practice''. CONCLUSION: This survey
      indicates that the EVCME approved congresses had a positive impact for the
      vascular surgeon by updating overall knowledge on vascular surgery; the majority
      of comments by the participants also indicates that EVCME is fulfilling its aim
      to bring as much evidence-based practice as possible into the daily work schedule
      of the surgeon by turning knowledge acquired by CME into performance of the
      participants.

PMID- 18091705
TI  - Interstitial magnetic resonance lymphography: is it a new method for the
      diagnosis of lymphedema?
AB  - AIM: The aim of this study was to evaluate the method of interstitial magnetic
      resonance lymphography (MRL) as an examination for the depiction of the lymphatic
      system in humans in comparison with the method of direct X-ray lymphography.
      METHODS: We studied 6 persons, 2 volunteers and 4 patients with clinical
      suspicion of lymphedema in lower extremities. We administered subcutaneous
      gadobutrol for the MRL with a volume of 5 mL composed of 4.5 mL of Gadobutrol
      mixed with 0.5 mL of lidocaine hydrochloride and after 7 days lipiodol in the
      lymph vessel for the X-ray direct lymphography (in 3 patients) in order to
      compare the findings of the two METHODS: We then followed up all individuals for
      7 days for any possible side effect of the contrast agents. RESULTS: Using MRL,
      we depicted the lymphatic system (lymph vessels and inguinal lymph nodes) of
      volunteers in 60 min. Moreover, in patients we depicted several abnormalities of
      the lymphatic system including decreased number of lymph vessels, lymphocele and
      ectatic lymph vessels. X-ray direct lymphography confirmed the findings of the
      MRL in all cases. No side effects were observed. CONCLUSION: In our pilot study,
      Gadobutrol seems to be a good contrast agent for the painless depiction of the
      lymphatic system in humans through interstitial MRL. More extensive studies are
      needed in order to establish the efficacy and the dosage of Gadobutrol.

PMID- 18091706
TI  - Normalisation of ultrasonic images of atherosclerotic plaques and reproducibility
      of grey scale median using dedicated software.
AB  - AIM: Image normalization using ''Adobe Photoshop'' a commercially available
      software package designed for photography has provided the means of making
      reproducible measurements of grey scale in ultrasonic images of carotid
      bifurcation plaques. A dedicated software package ''Plaque Texture Analysis'' has
      been developed by the authors that is simple to use, provides facilities for
      measurement of other texture features in addition to grey scale median (GSM) and
      allows the operator to save the normalised images, plaques and GSM measurements
      in a database for subsequent analysis. The aim of the study was to determine (a)
      the intraobserver variability of GSM when the same plaque images were analysed
      using both Adobe Photoshop and the dedicated software and (b) the interobserver
      variability when the same plaque images were analysed using the dedicated
      software by different observers. METHODS: A sample of 33 images of carotid
      bifurcation plaques (16 symptomatic and 17 asymptomatic) producing greater than
      50% stenosis of the internal carotid artery were analysed by two observers.
      RESULTS: The intraclass correlation coefficient and correlation coefficient (r)
      for GSM were 0.992 (95% CI 0.984 to 0.996) and 0.992 respectively for the first
      observer (MG); they were 0.986 (95% CI 0.972 to 0.993) and 0.987 respectively for
      the second observer (AN). The interobserver intraclass correlation coefficient
      and correlation coefficient (r) were 0.932 (95% CI 0.863 to 0.967) and 0.933
      respectively. CONCLUSION: These findings and the automatic saving of the
      normalised images and measurements in a database for subsequent statistical
      analysis make the ''Plaque Texture Analysis'' software a powerful research tool.

PMID- 18091708
TI  - The evolution of lower limb amputation through the ages. Historical note.
AB  - The aim of this study was to highlight the important stages of the evolution of
      limb amputation through the ages through the search of the relevant international
      literature. Limb amputation is one of the most serious surgical operations, which
      is associated with high mortality and morbidity. Evidence regarding the execution
      of limb amputation can be found back in Neolithic times. The most important steps
      in the evolution of the technique of limb amputation were made in the 16th, 17th,
      and 18th centuries when A. Pare' introduced the vessel ligation and the French
      barber surgeon Morell introduced the use of a tourniquet to reduce the bleeding.
      During the same period, from the ''one-stage circular cut'' the technique evolved
      to either ''three-stage circular cut'' or to ''flap amputation'', single or
      double. Limb amputation represents one of the oldest and most serious surgical
      operations. Its evolution parallels the maturation process of surgery, with the
      major developments in the technique to have been made from the 16th to the 18th
      century. In the beginning of the 21st century, limb amputation appears to be a
      safe operation ending up with a functional stump.

PMID- 18091707
TI  - Clinical and capillaroscopic evaluation in the treatment of chronic venous
      insufficiency with Ruscus aculeatus, hesperidin methylchalcone and ascorbic acid
      in venous insufficiency treatment of ambulatory patients.
AB  - AIM: Clinical and capillaroscopic evaluation of an association of Ruscus
      aculeatus, hesperidin methylchalcone (HMC) and ascorbic acid in chronic venous
      insufficiency METHODS: A prospective, multicenter and open clinical study.
      Chronic venous insufficiency patients were studied using clinical, etiological,
      anatomical, physiological classification (CEAP) symptom scale. Symptomatology,
      CEAP scale, and baseline, 2-, 4-, 6- and 8-week skin capillaroscopy were
      assessed. Treatment consisted of two capsules per day of Ruscus aculeatus 150
      mg/HMC 150 mg/ascorbic acid 100 mg during 8 weeks. RESULTS: A total of 124
      patients were studied, 109 female (89.28%), with a mean age of 52.5 (33-80+9.8).
      Initial intense reports were 79% pain, 85% heaviness, 74% cramps, 82% edema,
      decreasing to 20%, 12%, 8% and 14%, respectively, within two weeks, and
      symptomatology being absent at the end of treatment. Capillaroscopy changes at
      treatment completion were: 98% to 20% inter-capillary fluid decrease; 80% to 20%
      efferent loop thickening; 5% to 2% peri-capillary bed, and 5% to 4% mega
      capillaries. CONCLUSION: Severe symptom decrease started from the second week
      until there were no symptoms at the end of treatment. It is the first time
      morphologic changes were observed in chronic venous insufficiency through
      capillaroscopy following a pharmacological intervention. Capillary-level effect
      was proportional to symptom decrease. Improvement was seen from the second week
      of treatment.

PMID- 18091709
TI  - On infections and ischemic heart diseases.

PMID- 18091710
TI  - On acute respiratory tract infections and acute myocardial infarction. New data
      confirm previous findings.

PMID- 18091711
TI  - Clinical aspect and survival rates in subject with oral cancer: a retrospective
      cohort study.
AB  - AIM: The aim of this study was to describe and evaluate survival in a group of
      patients with oral malignant neoplasias, observed at the Unit of Oral Pathology
      and Medicine, University of Milan, between February 1995 and September 2005.
      METHODS: This retrospective study considered the clinical histories and
      anamnestic profiles of a group of 108 patients with malignant oral neoplasms. A
      sample of 72 out of these 108 patients was identified, for whom follow-up data
      were available for at least 4 months from the date of diagnosis. Survival times
      for this group were then evaluated. RESULTS: In this group of 108 patients, 103
      were affected by squamous cell carcinoma. The ratio of male to female patients
      was 1.1:1.0 and the average age at the time of diagnosis was 64.9 years. In 44
      out of 91 cases, the site affected was the tongue and in 28 out of 45 cases, the
      lesion was at an early stage (TNM 1 and 2) at the time of diagnosis. Survival in
      the group of 72 considered was 84% at 2 years from diagnosis and 55% at 5 years.
      Diagnosis before the age of 65 favoured a positive prognosis (P=0.01), as did
      lesions diagnosed at TNM 1 stage, though this was not statistically significant
      (P=0.1). CONCLUSION: The data provided in this retrospective study were
      consistent with previous reports of survival rates at 5 years from diagnosis and
      the improved prognosis for patients diagnosed before the age of 65. The only
      finding that was different from previous studies was the gender distribution,
      which in this study was almost equal.

PMID- 18091712
TI  - Five-year follow-up of temporomandibular disorders and other musculoskeletal
      symptoms in dental students.
AB  - AIM: The aim of this epidemiologic study was to evaluate the intensity and
      variation of temporomandibular disorders and other musculoskeletal symptoms in a
      population of dental students during the five years of Dental School. METHODS: A
      0-to-3 numeric scale questionnaire (0=absence of the symptom, 1=mild intensity,
      2=moderate intensity, 3=severe intensity) was submitted to all the students
      enrolled in the first year of the Dental School at the University of Saint Joseph
      (Beirut, Lebanon). The same questionnaire was filled out by the same students
      every year until they reached the fifth (last) year. RESULTS: Temporomandibular
      disorders and musculoskeletal symptoms were generally of mild intensity and
      fluctuating in time. No significant differences were found among years in the
      intensity of earache, headache, face pain, arm symptoms, neck pain, and
      toothache. Ear stuffiness decreased from the first to the third and fifth year.
      Temporomandibular joint pain, temporomandibular joint sounds, upper back pain,
      and lower back pain showed a similar trend generally increasing from the first
      and second years to the third year, and then decreasing until the fourth and
      fifth years. CONCLUSION: A higher risk of developing such symptoms associated
      with dental work in the laboratory can be hypothesized in case of improper
      ergonomics.

PMID- 18091713
TI  - Odontoma: retrospective study and confocal laser scanning microscope analysis of
      52 cases.
AB  - AIM: The aim of this study was to perform a retrospective analysis of 52 cases of
      odontoma treated at the Department of Dentistry and Surgery, University of Bari,
      in the period 1971-2005. METHODS: The odontogenic tumors were diagnosed as
      complex or compound odontoma following histological analysis and clinical
      radiological examination, and applying the 2005 WHO classification. The data
      analysis was conducted by considering the following factors: gender, age, site of
      the lesion, association with impacted teeth, aplasia, presence of supernumerary
      teeth as well as preoperative diagnosis by panoramic and periapical radiographs.
      Biopsy tissue samples were conventionally processed for histopathologic paraffin
      embedding and then were observed by optical microscopy and subsequently by
      confocal laser scanning microscopy (CLSM) in autofluorescence. RESULTS: Thirty
      specimens (57.6%) were from females and 22 (42.3%) were from males patients. The
      patients' age ranged from 5 to 75 years. Fifty-one percent of the specimens were
      excised from the mandible. In the maxilla, the most common location for odontomas
      was the anterior region. Most odontomas were associated with impacted teeth and
      only in one case there was an odontoma instead of a permanent tooth. CONCLUSION:
      Odontomas are considered hamartomatous malformations whose diagnosis is generally
      formulated by routinary radiographic examination. The CLSM analysis could help in
      diagnosis and histopathological analysis showing well-defined follicular area
      entrapped in hard tissues and pointing out ghost cells, otherwise not
      identifiable by traditional microscopy.

PMID- 18091714
TI  - A systematic review on the outcome of surgical vs non-surgical procedure for the
      retreatment of periapical lesions.
AB  - The most common therapeutical options for the retreatment of teeth with
      periapical pathosis are orthograde treatment and periapical surgery. The aim of
      this review was to evaluate the outcomes of surgical versus non-surgical
      retreatment, in order to provide clinicians with evidence-based information for
      decision making process. Articles were retrieved by electronic search strategy
      and traditional searching. Articles were selected based on strict inclusion
      criteria. The first criterion was the success of retreatment, as determined by
      clinical and radiographic criteria. The outcomes were further dichotomized
      according to functionality criteria. Two randomized trials (RCTs) were found. One
      hundred and twenty-six teeth were followed up after one year, and 82 after 4
      years. The success rate for surgical treatment after one year was slightly better
      than non-surgical: 90.7% vs 80.6%, respectively, according to functional
      criteria. At the four-year evaluation (40 surgically treated and 42 non
      surgically treated cases from 1 RCT) the outcomes were similar. A higher early
      post-operative discomfort was reported for surgically treated cases. There is no
      apparent advantage of using a surgical or non-surgical approach for the
      retreatment of periapical lesions in terms of long-term outcome. The choice
      between the two procedures should rely upon factors other than the mere treatment
      outcome, such as patient's initial clinical situation, patient's preference,
      operator's experience and skill, complication risk, technical feasibility, and
      overall treatment cost. More well-designed RCTs should be performed with a large
      sample size and at least 4 years follow-up, using modern instrumentation and
      materials, to detect a true difference in the long term between the outcomes of
      the two alternative treatments, if any exists.

PMID- 18091715
TI  - Endodontic treatment of a fused tooth. Report of a case.
AB  - Dental fusion, a rare developmental anomaly present in 0.2% of the general
      population, consists of the union of two teeth originating from two different
      tooth germs. The irregular coronal morphology and the complex endodontic anatomy,
      characterized by the partial or total union of the pulp chambers, together with
      the peculiarity of the root canal systems, make diagnosis, therapy and
      rehabilitation difficult. The authors describe the endodontic treatment of a
      permanent lower second molar fused with a third molar and having four root
      canals.

PMID- 18091716
TI  - Submandibular cellulitis (Ludwig's angina) associated to a complex odontoma
      erupted into the oral cavity. Case report and literature review.
AB  - The clinical presentation of Ludwig's angina consists in a severe expanding
      cellulitis causing swelling of the floor of the mouth, tongue and submandibular
      region, thus resulting in a possible obstruction of the airway and in a rapid
      progress in deep neck soft tissue infection and mediastinitis with potentially
      fatal consequences. Frequently, submandibular cellulitis develops from an acute
      infection spreading from the lower molar teeth. Mandibular fractures, traumatic
      laceration of the floor of the mouth, and peritonsillar abscesses are other
      concomitant clinical features. A case of Ludwig's angina associated with a large
      erupted odontoma and with a deeply impacted third molar displaced to the border
      of the mandible is described. The patient was affected by enlargement of
      submandibular space, marked face swelling causing an evident face deformity,
      tenderness and redness of the neck and limited movement of the neck and mouth. In
      the past, Ludwig's angina was frequently fatal, however aggressive surgical and
      medical therapy have significantly reduced the mortality rate. The reported case
      can be considered as important, not only because of the rarity of the odontoma
      eruption in the oral cavity, but mainly for the extent of the clinical
      manifestation of a lesion usually described in literature as asymptomatic.

PMID- 18091717
TI  - White sponge nevus. A case report.
AB  - White sponge nevus is a rare autosomal dominant hereditary disorder manifesting
      upon physical examination as white symmetric, diffuse, thickened, corrugated or
      velvety plaques on the oral, esophageal or genital mucosa. They are also found to
      be bilateral and asymptomatic. The tissue changes can be present at birth or
      manifest during childhood or adolescence, and this disorder occurs in females
      more than in males. It is a benign condition since cases of malignancy have not
      been reported, and it does not require treatment. Therefore, it is important to
      establish a differential diagnosis to rule out other white lesions that occur on
      the oral mucosa, mainly those in which there is a risk of malignancy. A case of
      white sponge nevus is reported along with a discussion on the differential
      diagnosis and clinical management.

PMID- 18091718
TI  - Does surgically induced weight loss decrease mortality?

PMID- 18091719
TI  - Can acute administration of pamidronate help to preserve bone mass in children
      with severe burn injury?

PMID- 18091720
TI  - Amplitude-integrated EEG--useful for early outcome prediction after birth
      asphyxia?

PMID- 18091721
TI  - Association between beta-blocker use and reduced mortality after vascular surgery
      in patients with kidney disease.

PMID- 18091722
TI  - Assessing the vascular effects of early erythropoietin use in pediatric renal
      transplant recipients.

PMID- 18091723
TI  - A map of human cancer signaling.
AB  - We conducted a comprehensive analysis of a manually curated human signaling
      network containing 1634 nodes and 5089 signaling regulatory relations by
      integrating cancer-associated genetically and epigenetically altered genes. We
      find that cancer mutated genes are enriched in positive signaling regulatory
      loops, whereas the cancer-associated methylated genes are enriched in negative
      signaling regulatory loops. We further characterized an overall picture of the
      cancer-signaling architectural and functional organization. From the network, we
      extracted an oncogene-signaling map, which contains 326 nodes, 892 links and the
      interconnections of mutated and methylated genes. The map can be decomposed into
      12 topological regions or oncogene-signaling blocks, including a few 'oncogene
      signaling-dependent blocks' in which frequently used oncogene-signaling events
      are enriched. One such block, in which the genes are highly mutated and
      methylated, appears in most tumors and thus plays a central role in cancer
      signaling. Functional collaborations between two oncogene-signaling-dependent
      blocks occur in most tumors, although breast and lung tumors exhibit more complex
      collaborative patterns between multiple blocks than other cancer types.
      Benchmarking two data sets derived from systematic screening of mutations in
      tumors further reinforced our findings that, although the mutations are
      tremendously diverse and complex at the gene level, clear patterns of oncogene
      signaling collaborations emerge recurrently at the network level. Finally, the
      mutated genes in the network could be used to discover novel cancer-associated
      genes and biomarkers.

PMID- 18091724
TI  - Modeling the regulatory network of histone acetylation in Saccharomyces
      cerevisiae.
AB  - Acetylation of histones plays an important role in regulating transcription.
      Histone acetylation is mediated partly by the recruitment of specific histone
      acetyltransferases (HATs) and deacetylases (HDACs) to genomic loci by
      transcription factors, resulting in modulation of gene expression. Although
      several specific interactions between transcription factors and HATs and HDACs
      have been elaborated in Saccharomyces cerevisiae, the full regulatory network
      remains uncharacterized. We have utilized a linear regression of optimized
      sigmoidal functions to correlate transcription factor binding patterns to the
      acetylation profiles of 11 lysines in the four core histones measured at all S.
      cerevisiae promoters. The resulting associations are combined with large-scale
      protein-protein interaction data sets to generate a comprehensive model that
      relates recruitment of specific HDACs and HATs to transcription factors and their
      target genes and the resulting effects on individual lysines. This model provides
      a broad and detailed view of the regulatory network, describing which
      transcription factors are most significant in regulating acetylation of specific
      lysines at defined promoters. We validate the model, both computationally and
      experimentally, to demonstrate that it yields accurate predictions of these
      regulatory mechanisms.

PMID- 18091725
TI  - Deriving structure from evolution: metazoan segmentation.
AB  - Segmentation is a common feature of disparate clades of metazoans, and its
      evolution is a central problem of evolutionary developmental biology. We evolved
      in silico regulatory networks by a mutation/selection process that just rewards
      the number of segment boundaries. For segmentation controlled by a static
      gradient, as in long-germ band insects, a cascade of adjacent repressors
      reminiscent of gap genes evolves. For sequential segmentation controlled by a
      moving gradient, similar to vertebrate somitogenesis, we invariably observe a
      very constrained evolutionary path or funnel. The evolved state is a cell
      autonomous 'clock and wavefront' model, with the new attribute of a separate
      bistable system driven by an autonomous clock. Early stages in the evolution of
      both modes of segmentation are functionally similar, and simulations suggest a
      possible path for their interconversion. Our computation illustrates how complex
      traits can evolve by the incremental addition of new functions on top of pre
      existing traits.

PMID- 18091726
TI  - Brain expression--is it all in our SNPs?

PMID- 18091728
TI  - Do exercise and advice help to improve the symptoms of subacute low back pain?

PMID- 18091727
TI  - Synthetic biology: promises and challenges.

PMID- 18091729
TI  - Does calcium supplementation reduce the risk of osteoporotic fracture and bone
      loss?

PMID- 18091730
TI  - Is surgery more effective than nonsurgical treatment for the management of
      patients with degenerative spondylolisthesis?

PMID- 18091733
TI  - Blood pressure variability: the challenge of variation.

PMID- 18091734
TI  - Plasma renin activity for predicting antihypertensive drug efficacy.

PMID- 18091736
TI  - Ventricular repolarization in hypertension: beyond Bazett.

PMID- 18091737
TI  - Pretreatment plasma renin activity levels correlate with the blood pressure
      response to telmisartan in essential hypertension.
AB  - BACKGROUND: Although the therapeutic response to angiotensin II receptor blockers
      (ARBs) is assumed impaired in patients with low-renin hypertension, data are
      scarce about the association between levels of plasma renin activity (PRA) before
      treatment and response of ambulatory blood pressure (ABP) to ARBs in essential
      hypertension. METHODS: We prospectively studied 11 untreated Japanese patients
      with essential hypertension (3 women and 8 men, mean age: 50 +/- 9 (mean +/- SD)
      years). After a 4-week drug-free period, telmisartan 20-40 mg was administered
      orally once daily for 8 weeks. PRA levels were measured before treatment. The
      first ABP measurement was performed at the end of the drug-free period and the
      second measurement at the end of the treatment period with telmisartan. RESULTS:
      Telmisartan significantly decreased the 24-h ABP by 12 +/- 11 mm Hg systolic (P <
      0.01) and 9 +/- 8 mm Hg diastolic (P < 0.01). Reductions in the 24-h systolic and
      diastolic ABPs were significantly greater in five patients with higher renin
      levels (> or =0.65 ng/ml/h) than in six patients with lower renin levels (<0.65
      ng/ml/h) by 18 mm Hg systolic (P < 0.001) and 11 mm Hg diastolic (P < 0.05).
      Changes in the 24-h systolic and diastolic ABPs significantly correlated with log
      PRA before treatment. CONCLUSIONS: The ABP lowering effects of telmisartan were
      dependent on PRA levels before treatment in patients with essential hypertension.
      Measurement of PRA levels before treatment is thought to be useful for prediction
      of the ABP lowering effects of telmisartan.

PMID- 18091738
TI  - Carryover effects after cessation of drug treatment: trophies or dreams?
AB  - BACKGROUND: In randomized trials of primary prevention, there has been interest
      in the persistence of a beneficial effect of therapy after treatment has been
      stopped. We investigated the impact of measurement error in the outcome on
      results of the trial of preventing hypertension (TROPHY), a trial of candesartan
      vs. placebo for preventing hypertension in prehypertensive subjects. METHODS: We
      simulated the TROPHY study design, assuming that candesartan reduced blood
      pressure by 8/6 mm Hg during treatment, but had no carryover effect after
      treatment stopped. We simulated individual true blood pressures in the TROPHY
      eligible range of 130-140 mm Hg for systolic blood pressure and 80-90 mm Hg for
      diastolic blood pressure, and added individual measurement variability. As in
      TROPHY, incident hypertension was defined as any three occurrences of systolic
      blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg. RESULTS: In the
      absence of any carryover effect, typical incidence curves for time to
      hypertension were similar to those from TROPHY. A significant difference in
      cumulative incidence 2 years after stopping treatment was detected in 80%
      simulated studies, giving a Type I error rate of 80%. CONCLUSIONS: The published
      data from TROPHY are consistent with a lack of carryover effect of candesartan.

PMID- 18091739
TI  - Relationship between the metabolic syndrome and the development of hypertension
      in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2).
AB  - BACKGROUND: The metabolic syndrome is a predictor of diabetes and coronary
      events. We hypothesized that it also predicts hypertension. METHODS: A total of
      1,944 subjects (901 men and 1,043 women; age 46 +/- 12 years) from the Hong Kong
      Cardiovascular Risk Factor Prevalence Survey were recruited in 1995-1996 and
      restudied in 2000-2004. The prevalence of hypertension and factors predicting its
      development were determined. RESULTS: In 2000-2004, hypertension was found in
      23.2% of the men and 17.2% of the women. Of the 1,602 subjects who were
      normotensive at baseline, 258 subjects developed hypertension after a median
      interval of 6.4 years. According to the National Cholesterol Education Program
      (NCEP) and International Diabetes Federation (IDF) criteria, the hazard ratios
      associated with the metabolic syndrome were 1.89 (95% confidence interval (CI):
      1.41-2.54) and 1.72 (95% CI: 1.24-2.39), respectively. The positive and negative
      predictive values of the metabolic syndrome for identifying subjects who will
      develop hypertension in this population were 34.7 and 85.4% (NCEP criteria), and
      33.1 and 85.5% (IDF criteria), respectively. The development of hypertension was
      related to the number of components of the metabolic syndrome (other than raised
      blood pressure), present in men (P = 0.003) and in women (P = 0.001). Using
      multivariate analysis, age, baseline systolic blood pressure (SBP), body mass
      index (BMI), and the triglycerides/high-density lipoprotein (HDL) ratio were
      found to be significant predictors of the development of hypertension. Compared
      with optimal blood pressure, the hazards of developing hypertension associated
      with normal or high-normal blood pressure were 2.31 (95% CI: 1.68-3.17) and 3.48
      (95% CI: 2.52-4.81), respectively. CONCLUSIONS: Blood pressure, when not optimal,
      is the predominant predictor of hypertension. The metabolic syndrome contributes
      to the risk, especially when blood pressure is optimal.

PMID- 18091740
TI  - Hydroxyhydroquinone interferes with the chlorogenic acid-induced restoration of
      endothelial function in spontaneously hypertensive rats.
AB  - BACKGROUND: Coffee is a rich source of antioxidative polyphenols, but
      epidemiological studies and interventional trials have failed to demonstrate any
      clear beneficial effects of coffee consumption on hypertension. The interaction
      between hydroxyhydroquinone (HHQ) and 5-caffeoylquinic acid (CQA) was examined,
      in an attempt to understand the controversial effects of coffee on hypertension.
      METHODS: Male Wistar Kyoto (WKY) rats or spontaneously hypertensive rats (SHRs,
      14 weeks old) were divided into the following four groups; those on a control
      diet, 0.005% HHQ diet, 0.5% CQA diet, and HHQ plus CQA diet. The rats were fed
      the above diets for 8 weeks, and the tail arterial blood pressure was monitored
      in conscious rats at 2-week intervals. Urinary nitric oxide (NO) metabolites and
      hydrogen peroxide (H(2)O(2)) excretion were measured 8 weeks after the start of
      the experiment. Endothelium-dependent and -independent vasorelaxant responses and
      immunohistochemical staining for nitrotyrosine were examined in aortas. RESULTS:
      HHQ inhibited the CQA-induced improvement in hypertension, urinary NO metabolites
      or H(2)O(2) excretion, endothelial dysfunction, and nitrotyrosine deposits in
      aortas in SHR. However, the administration of HHQ alone had little effect on
      either strain. CONCLUSIONS: Based on the content ratio of HHQ and chlorogenic
      acids in coffee, HHQ interfered with the CQA-induced improvement in blood
      pressure and endothelial function in SHR. The results explain, at least in part,
      the conflicting action of coffee drinking on hypertension and vascular
      reactivity.

PMID- 18091741
TI  - Upregulation of endothelial and inducible nitric oxide synthase expression by
      reactive oxygen species.
AB  - BACKGROUND: The effect of reactive oxygen species (ROS) on nitric oxide synthase
      (NOS) expression remains uncertain. This study explored the effect of increased
      ROS activity on NOS expression in vitro in human coronary artery endothelial
      cells (HCAECs) grown in culture and in intact animals. METHODS: Endothelial NOS
      (eNOS) expression and nuclear factor kappaB (NFkappaB) activation were determined
      in HCAECs grown in culture and exposed to oxidative stress with xanthine-xanthine
      oxidase (X-XO) generated superoxide, H(2)O(2), or glutathione depletion with
      buthionine sulfoximine (BSO) for 24 h. In parallel experiments, cells were
      treated with a nitric oxide (NO) scavenger (hemoglobin), and with an NO donor S
      nitroso-N-acetyl penicillamine (SNAP)]. In addition, eNOS and inducible NOS
      (iNOS) expressions were determined in rats treated with either BSO or vehicle for
      48 h. RESULTS: Increases in ROS activity, achieved by exogenous superoxide and
      H(2)O(2) or by glutathione depletion, upregulated the expression of eNOS at both
      transcriptional and translational levels in HCAECs. Similar effects were seen
      with the non-radical NO scavenger, hemoglobin. The upregulatory action of
      hemoglobin on eNOS messenger RNA (mRNA) and protein expressions was overcome by
      the NO donor, SNAP, thereby suggesting that there is a negative feedback
      regulation of eNOS by NO. Nuclear translocation of NFkappaB (p65) was noted
      within 5 min of exposure to H(2)O(2) and at least 15 min after exposure to
      superoxide or BSO. Induction of oxidative stress by glutathione depletion led to
      upregulation of renal and aorta eNOS and iNOS in live animals. CONCLUSIONS: An
      increase in ROS activity upregulates NOS expression in vitro in HCAECs grown in
      culture, and also in vivo in animals. This effect appears to be, in part,
      mediated by limiting the availability of NO, thereby exerting a negative feedback
      influence on NOS expression through activation of NFkappaB.

PMID- 18091742
TI  - Inverse relationship between ambulatory arterial stiffness index and glomerular
      filtration rate in arterial hypertension.
AB  - BACKGROUND: Arterial stiffness and mild-to-moderate renal dysfunction are
      predictors of cardiovascular (CV) morbidity and mortality. Recently, the
      ambulatory arterial stiffness index (AASI) has been proposed as a surrogate index
      of arterial stiffness. It has been associated with an enhanced risk of stroke.
      The aim of our study was to assess the relationship between AASI and glomerular
      filtration rate (GFR) in a group of hypertensive patients with no CV
      complications. METHODS: A total of 143 untreated hypertensive subjects (mean age:
      44 +/- 12 years; men 57%), with serum creatinine <1.5 mg/dl, were enrolled. AASI
      was calculated as one minus the regression slope of diastolic on systolic blood
      pressure (BP) obtained by individual 24-h BP recordings. GFR was computed from
      the scintigraphic determination of the technetium-99m
      diethylenetriaminepentaacetic acid uptake within the kidneys, by the Gates'
      method. RESULTS: Hypertensive patients with AASI above the median value (n = 71)
      had lower GFR than those with AASI below the median (n = 72) (98.3 +/- 31 vs.
      122.4 +/- 32 ml/min/1.73 m(2); P < 0.001). This difference held even after
      adjustment for age and gender. The linear regression analysis disclosed a
      significant inverse correlation between GFR and AASI (r = -0.30; P < 0.001), that
      was replicated (beta = -0.19; P = 0.02) in a multiple regression model including,
      as independent variables (besides AASI), age, gender, high-density lipoprotein
      cholesterol, body mass index, 24-h pulse pressure (PP) and nocturnal reduction in
      BP. CONCLUSIONS: AASI is inversely related to GFR in arterial hypertension. This
      may help to explain the increased CV risk associated with mild-to-moderate renal
      dysfunction.

PMID- 18091743
TI  - Recent ventricular repolarization markers in resistant hypertension: are they
      different from the traditional QT interval?
AB  - BACKGROUND: Two electrocardiographic markers of ventricular repolarization
      abnormalities have been recently proposed: spatial T-wave axis deviation and
      T(peak)-T(end)-interval duration. The aim of this study was to evaluate these
      markers in patients with resistant hypertension, particularly their relationships
      with left ventricular mass (LVM) and geometric patterns, in comparison with the
      more traditional marker, the QTc interval. METHODS: In a cross-sectional study,
      810 resistant hypertensive patients were evaluated. Clinical, laboratory,
      electrocardiographic, 24-h blood pressures and echocardiographic variables were
      obtained. Maximum T(peak)-T(end)-interval duration (Tpe(max)) was considered
      prolonged if it was beyond the upper quartile value (120 ms), and the spatial T
      wave axis on the frontal plane was considered abnormally deviated if >105 degrees
      or < 15 degrees . Statistical analysis involved bivariate tests, multivariate
      logistic regression and analysis of covariance. RESULTS: Tpe(max)-interval
      prolongation, like QTc-interval prolongation, was found to be associated with
      body mass index, 24-h systolic blood pressure (SBP), indexed LVM, serum
      potassium, and heart rate. Abnormal T-axis deviation was associated with male
      gender, presence of coronary heart disease, serum creatinine, 24-h SBP, LVM, and
      serum potassium. All three repolarization parameters were shown to be associated
      with increased LVM, after adjustment for possible confounders. However, when
      included together into the same model, only abnormal T-axis and QTc-interval
      prolongation remained independently associated with LVM. All three parameters
      were also increased in patients with concentric hypertrophy geometric pattern.
      CONCLUSIONS: Both the recently proposed repolarization parameters are associated
      with increased LVM and hypertrophy in patients with resistant hypertension, but
      only abnormal T-wave axis deviation appears to have distinct and additive
      relationships to the more classic marker, the QTc interval. Their prognostic
      values should be addressed in prospective studies .

PMID- 18091744
TI  - Improvement of cardiac diastolic function by long-term centrally mediated
      sympathetic inhibition in one-kidney, one-clip hypertensive rabbits.
AB  - BACKGROUND: Hypertension is associated with left ventricular hypertrophy (LVH)
      and diastolic dysfunction. The sympathetic nervous system (SNS) is strongly
      implicated in these alterations. The possible beneficial effect of a centrally
      mediated sympathetic inhibition on the diastolic function in severe hypertension
      has never been studied. We have evaluated the cardiac effects (remodeling,
      diastolic and systolic functions) of a long-term treatment with a centrally
      acting drug, rilmenidine, in a model of severe renovascular hypertension.
      METHODS: One-kidney, one-clip (1K,1C) Goldblatt hypertensive rabbits were
      randomized in two groups, one receiving rilmenidine (5 mg/kg/day) for 6 weeks and
      the other treated with vehicle only. Hemodynamic effects and left ventricular
      (LV) remodeling were evaluated by serial tail cuff pressure measurements, and
      echocardiography every 15 days. These measurements were followed up with invasive
      hemodynamic measurements and histological analysis. RESULTS: Rilmenidine induced
      a decrease of 8% in blood pressure, a significant bradycardia (19% at 6 weeks
      after treatment) and an 18% reduction in LV mass, without reduction of ejection
      fraction (EF). These effects were accompanied by an improvement of the diastolic
      function, as shown by isovolumic relaxation time and decrease in Tau index, an
      E/A ratio reversion, and an Ea velocity increase. Moreover, reduction in the
      atrial (A) and atrial reverse (Ar) velocities, without any effect on LV filling
      pressures, was observed. CONCLUSIONS: In 1K,1C Goldblatt rabbits, which mimic
      most of the characteristics of human hypertensive cardiopathy, we have shown, for
      the first time, that a central inhibition of the SNS rapidly reverses cardiac
      hypertrophy and problems associated with primary LV relaxation, without negative
      inotropic action.

PMID- 18091745
TI  - Predictors of blood pressure response to the angiotensin receptor blocker
      candesartan in essential hypertension.
AB  - BACKGROUND: Response to antihypertensive drugs varies widely among individuals.
      METHODS: We studied characteristics that might be predictive of blood pressure
      (BP) response in 203 African-American and 236 non-Hispanic white subjects with
      essential hypertension treated with candesartan, 32 mg/day for 6 weeks, after a
      drug-free washout period of at least 4 weeks (baseline). Measurements at
      enrollment, baseline, and at the end of the treatment were incorporated into
      linear regression models to quantify their additive contributions to predicting
      response. RESULTS: Enrollment measurements predictive of a greater response were
      non-Hispanic white ethnicity, female gender, the interaction between ethnicity
      and gender, and lower body weight. Of baseline measurements, higher BP and higher
      plasma renin activity (PRA) made additional contributions to predicting a greater
      response. Of the measurements made at the end of the study, only a larger
      increase in PRA from baseline contributed to predicting a greater response. The
      combined effects of all the identified predictors accounted for 39 and 33% of the
      interindividual variation in systolic and diastolic BP responses, respectively (P
      < 0.001 for both). CONCLUSIONS: These results indicate that easily determined
      characteristics such as ethnicity, gender, body weight, as well as pretreatment
      levels of BP and PRA predict a substantial fraction of the BP response to
      candesartan and support the notion that characteristics associated with a poor
      response to diuretic therapy are associated with better responses to an
      angiotensin receptor blocker (ARB).

PMID- 18091746
TI  - Ascorbic acid decreases the binding affinity of the AT1 receptor for angiotensin
      II.
AB  - BACKGROUND: Ascorbic acid is an essential vitamin and a powerful antioxidant.
      Many studies have highlighted the benefits of ascorbic acid for chronic
      cardiovascular diseases such as hypertension in which angiotensin II (Ang II)
      plays an significant role. We therefore hypothesized that ascorbic acid could
      modify the pharmacological properties of the AT(1) receptor for Ang II. METHODS:
      Binding studies and Ca(2+) mobilization studies were performed with HEK293 cells
      stably expressing the AT(1) receptor for Ang II. Smooth muscle contraction
      studies were performed with rabbit aorta strips that endogenously express the
      AT(1) receptor. RESULTS: Scatchard analysis revealed that ascorbic acid decreased
      the binding affinity of the AT(1) receptor without modifying its maximal binding
      capacity. Ascorbic acid did not modify the binding affinity of the AT(2) receptor
      for Ang II or of the UT receptor for urotensin II. In single-cell Ca(2+) imaging
      assays, ascorbic acid reduced the frequency of intracellular Ca(2+) oscillations
      induced by a low dose of Ang II. In functional assays, ascorbic acid
      significantly diminished the contraction of rabbit aorta pre-contracted with Ang
      II but not those pre-contracted with urotensin II. CONCLUSIONS: Ascorbic acid
      decreases the binding affinity of the AT(1) receptor. These results offer a
      mechanistic explanation for the reported blood pressure lowering effect of
      ascorbic acid.

PMID- 18091747
TI  - Effects of an ARB on endothelial progenitor cell function and cardiovascular
      oxidation in hypertension.
AB  - BACKGROUND: Angiotensin II (Ang II) receptor blocker (ARB) has been reported to
      have protective effects on the cardiovascular system independent of blood
      pressure reduction. Endothelial progenitor cells (EPCs) play a significant role
      in neovascularization of ischemic tissue. The average lifespan of EPCs was
      recently reported to be shortened by oxidative stress and regulated by anti
      oxidative mechanisms. It has been reported that EPCs are present in peripheral
      blood and have the ability to repair cardiovascular damage. We investigated the
      effects of an ARB, candesartan, on EPC function and cardiovascular oxidation in
      salt-loaded, stroke-prone, spontaneously hypertensive rats (SHR-SP) in vivo.
      METHODS: Salt-loaded SHR-SP were treated with candesartan (1 mg/kg/day), a
      diuretic (trichlormethiazide, TCM, 1.6 mg/kg/day), or an antioxidant (tempol, 5
      mg/kg/day) for 2 weeks. Peripheral blood mononuclear cells (MNCs) were isolated
      and cultured to assay EPC colony formation and migration. Oxidative stress in
      EPCs was evaluated by thiobarbituric acid reactive substance (TBARS) assay. We
      evaluated messenger RNA (mRNA) expression of c-kit in the heart, the renin
      angiotensin system (RAS) in EPC colonies, and reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase subunit in cardiovascular organs. RESULTS:
      Candesartan and tempol, but not TCM, markedly increased EPC colony number in SHR
      SP and reduced TBARS. Candesartan also significantly decreased mRNA expression of
      NADPH oxidase subunits in cardiovascular organs and increased cardiac c-kit mRNA
      expression. EPCs expressed mRNAs of renin, cathepsin D, chymase, and Ang II type
      1 and type 2 receptors. CONCLUSIONS: Candesartan, an ARB, improves EPC
      dysfunction and increases cardiac c-kit expression through the anti-oxidative
      mechanism in hypertension. The local RAS induces oxidative stress and regulates
      the EPC functions.

PMID- 18091748
TI  - Calcium channel blockers suppress cytokine-induced activation of human
      neutrophils.
AB  - BACKGROUND: Neutrophils, in concert with proinflammatory cytokines, play an
      important role in the progression of atherosclerosis. Calcium channel blockers
      are commonly used in the treatment of hypertension, and their pleiotropic
      effects, other than the lowering of blood pressure, have been recently
      recognized. METHODS: We studied the effects of various calcium channel blockers
      (amlodipine, nicardipine, cilnidipine, benidipine, efonidipine, nifedipine,
      azelnidipine, verapamil, and diltiazem; each being used at 5 and 10 micromol/l)
      on superoxide (O(2)(-)) release, migration, and signaling pathways in human
      neutrophils stimulated by granulocyte-macrophage colony-stimulating factor (GM
      CSF) or tumor necrosis factor-alpha (TNF-alpha). RESULTS: GM-CSF-induced O(2)(-)
      release was suppressed by amlodipine, nicardipine, and cilnidipine, whereas TNF
      alpha-induced O(2)(-) release was suppressed by amlodipine, nicardipine,
      cilnidipine, benidipine, efonidipine, nifedipine, and azelnidipine. TNF-alpha
      induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt,
      but not p38 mitogen-activated protein kinase (MAPK), was attenuated by
      nicardipine, cilnidipine, benidipine, efonidipine, and azelnidipine. By contrast,
      GM-CSF-induced phosphorylation of ERK, p38, and Akt was affected by none of the
      blockers. GM-CSF-induced neutrophil migration was also suppressed by amlodipine
      and nicardipine, but not by azelnidipine, when these blockers were assessed for
      their effect on neutrophil migration. CONCLUSIONS: These findings suggest that
      (i) some calcium channel blockers can suppress cytokine-induced neutrophil
      activation, leading to possible prevention of the progression of atherosclerosis;
      and (ii) that activation of the ERK and phosphatidylinositol 3-kinase (PI3K)/Akt
      pathways, induced by TNF-alpha but not by GM-CSF, is selectively affected by some
      blockers.

PMID- 18091749
TI  - Blood pressure variability causes spurious identification of hypertension in
      clinical studies: a computer simulation study.
AB  - BACKGROUND: The blood pressure (BP) of an individual varies considerably from day
      to day. Hypertension is commonly identified based on the average of two BPs taken
      at each of two visits, a practice consistent with current guidelines. We
      hypothesized that (i) in the setting of high-normal BP ("prehypertension"), this
      practice results in frequent spurious detection of hypertension, and (ii) that
      random, spurious detection of hypertension and flawed study design together
      explain why in the Trial of Preventing Hypertension (TROPHY) study candesartan
      appeared to suppress the development of hypertension for 2 years after cessation
      of therapy. METHODS: We used Monte Carlo simulation to quantify spurious
      detection of hypertension at repeated clinic visits in one million subjects with
      unchanging usual systolic BPs (SBPs) between 130 and 139 mm Hg and normal BP
      variability. Criteria for identifying hypertension derived from Rosner and Polk,
      Seventh Report of the Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure (JNC 7), and the Trials of
      Hypertension Prevention (TOHP), TROPHY, and Framingham studies were applied to
      Canadian Heart Health Survey data. On the basis of these simulations, we created
      a three-parameter model of Kaplan-Meier curves recorded in the TROPHY study. We
      used the model to analyze the rates at which hypertension was identified in the
      TROPHY study. RESULTS: TROPHY criteria spuriously identify hypertension in 76% of
      subjects over 18 clinic visits. Higher rates of spurious detection of
      hypertension are seen with JNC 7, TOHP and Framingham study criteria. Even highly
      conservative criteria falsely identify hypertension in 27% of subjects over 18
      visits. Our three-parameter model suggests no postdiscontinuation benefit of
      candesartan. CONCLUSIONS: When applied over multiple visits, current criteria for
      detecting hypertension are intolerant of normal BP variation. The use of
      conservative criteria would reduce spurious identification of hypertension. The
      apparent long-term beneficial effect of candesartan seen in the TROPHY study can
      be explained by an inadequate method for detecting hypertension, and flawed study
      design.

PMID- 18091750
TI  - Impaired diurnal blood pressure variation and all-cause mortality.
AB  - BACKGROUND: Most healthy people exhibit a decrease in systolic blood pressure
      (SBP) at night. A drop of <10% from mean daytime values, "non-dipping," is
      associated with kidney disease and cardiovascular events. We hypothesized that
      non-dipping would predict all-cause mortality. METHODS: Consecutive patients
      referred for ambulatory blood pressure (BP) monitoring at the Cleveland Clinic
      between 1994 and 2004 were included. Mean daytime (6 AM-11 PM) and nighttime (11
      PM-6 AM) SBP values were calculated. We examined diurnal BP variation as a
      continuous variable, ((Mean daytime SBP - Mean nighttime SBP)/(Mean daytime SBP))
      x 100%, and also as a categorical variable, defining "non-dipping" as a nocturnal
      SBP drop of <10%; subjects who exhibited non-dipping were defined as "non
      dippers" and the others as "dippers." All-cause mortality was ascertained from
      the Social Security Death Index. RESULTS: Of the 621 patients included in the
      study, 261 were dippers and 360 were non-dippers. Non-dippers were older (P <
      0.0001), more likely to be non-white (P < 0.05), and had higher rates of smoking,
      diabetes, hypertension, coronary artery disease, congestive heart failure, and
      renal insufficiency (P < 0.01 for all). Over a mean follow-up of 6.3 years, 61
      patients died, including 10 dippers (3.8%) and 51 non-dippers (14.2%). The
      unadjusted hazard ratio for death based upon a decrement in the dipping
      percentage from the 75th to 25th percentile was 2.22 (95% confidence interval
      1.64-2.95; P < 0.0001). This was attenuated after adjustment for comorbid
      conditions, including mean 24-h SBP and renal function: adjusted hazard ratio
      1.62 (1.14-2.24; P < 0.005). CONCLUSIONS: Blunted diurnal BP variation is a
      strong predictor of death, but this may be accounted for, in large part, by its
      association with other cardiovascular risk factors.

PMID- 18091751
TI  - Oxidative stress contributes to renovascular hypertension.
AB  - BACKGROUND: Oxidative stress is a state in which excess reactive oxygen species
      (ROS) overwhelm endogenous antioxidant systems. It is known that this state has
      been involved in the development of hypertension. On the basis of previous data,
      we hypothesized that overactivity of NAD(P)H oxidase-derived ROS and the lowered
      activity of CuZnSOD, an endogenous antioxidant within the rostral ventrolateral
      medulla (RVLM), could contribute to 2K-1C (two-kidney one-clip) hypertension.
      Moreover, to test the functional significance of whether oxidative stress was
      involved in the maintenance of sympathetic vasomotor tone and blood pressure in
      2K-1C hypertension, we administered Ascorbic Acid (Vit C), an antioxidant, into
      the RVLM or systemically. METHODS: Experiments were performed in male Wistar rats
      (6 weeks after renal surgery--Goldblatt hypertension model--2K-1C). The mRNA
      expression of NAD(P)H oxidase subunits (p47phox and gp91phox) and CuZnSOD were
      analyzed in the RVLM using real-time PCR technique. The mean arterial blood
      pressure, heart rate, and renal sympathetic nerve activity were analyzed. Blood
      samples were collected and measured using thiobarbituric acid-reactive substances
      (TBARS). RESULTS: The mRNA expression of NAD(P)H oxidase subnits (p47phox and
      gp91pox) was greater in 2K-1C compared to the control group in the RVLM, and
      CuZnSOD expression was similar in both groups. In the RVLM, Vit C resulted in a
      fall in arterial pressure and in the sympathetic activity only in the 2K-1C rats.
      Thiobarbituric acid-reactive substances (TBARS) were significantly greater in 2K
      1C rats and the acute infusion of Vit C significantly decreased arterial pressure
      and renal sympathetic activity in 2K-1C. CONCLUSIONS: The results support the
      idea that an increase in oxidative stress within the RVLM and systemically plays
      a major role in maintaining high arterial blood pressure and sympathetic drive in
      2K-1C hypertension.

PMID- 18091752
TI  - Lowering the threshold for defining microalbuminuria: effects of a lifestyle
      metformin intervention in obese "normoalbuminuric" non-diabetic subjects.
AB  - BACKGROUND: We investigated whether levels of albuminuria (urinary albumin
      excretion (UAE)) below those conventionally accepted as microalbuminuria (<30
      mg/day) are sensitive to correction of obesity and obesity-related risk factors.
      METHODS: The effects of a 12-month lifestyle modification-metformin program were
      evaluated in otherwise healthy overweight/obese "normoalbuminuric" subjects:
      group I with UAE of <10 mg/day (n = 23) and group II with UAE of 10-29 mg/day (n
      = 18). RESULTS: The subjects of group II were older and heavier, and had higher
      blood pressure (BP) and lower high-density lipoprotein (HDL) levels, than those
      of group I. Creatinine clearances were also higher in group II (148 +/- 14
      ml/min) than in group I (108 +/- 9 ml/min). Although the intervention induced
      comparable reductions in obesity, BP, lipids and insulin levels in both groups,
      UAE was significantly reduced in group II (9.1 +/- 1.8 mg/24 h; 60% reduction; P
      < 0.001), and non-significantly in group I (0.75 +/- 0.5 mg/day; 12% reduction; P
      > 0.1). Additionally, greater reduction in creatinine clearance was observed in
      subjects with higher UAE rates. After the intervention, both groups achieved
      similar UAE rates (5.7 +/- 0.9 and 5.2 +/- 1.0 mg/day; P > 0.10). Basal UAE was
      related to the subjects' creatinine clearance (r = 0.38; P = 0.04). For both
      groups together, intervention-induced changes in UAE rates were not significantly
      related to BP, age, or body weight. However, for group II subjects, BP and UAE
      reduction were positively associated (r = 0.44; P = 0.03). CONCLUSIONS: UAE of 10
      29 mg/day (hyperalbuminuria), below the conventionally used limit to define
      microalbuminuria, is already associated with a more adverse cardiovascular risk
      profile, and is exquisitely sensitive to interventions that reduce obesity, BP,
      and insulin resistance.

PMID- 18091753
TI  - Neuronal nitric oxide synthase-deficient mice have impaired renin release but
      normal blood pressure.
AB  - BACKGROUND: Nitric oxide deficiency is involved in the development of
      hypertension, but the mechanisms are currently unclear. This study was conducted
      to further elucidate the role of neuronal nitric oxide synthase (nNOS) in blood
      pressure regulation and renin release in relation to different sodium loads.
      METHODS: Blood pressure and heart rate were measured telemetrically and assessed
      during periods of physical activity and inactivity. Urinary solute excretion was
      measured by metabolism cages and plasma renin concentration (PRC) was determined
      by radioimmunoassay; all in nNOS knockout (nNOS(-/-)) and wild-type (nNOS(+/+))
      mice after 10 days of low (0.01% NaCl) and high (4% NaCl) sodium diets. RESULTS:
      The resting heart rate was reduced in nNOS(-/-) mice, but the two genotypes had
      similar blood pressure during the low (nNOS(+/+) 104 +/- 2 mm Hg; nNOS(-/-) 103
      +/- 2 mm Hg) and high (nNOS(+/+) 107 +/- 3 mm Hg; nNOS(-/-) 108 +/- 2 mm Hg)
      sodium diets. During the high sodium diet, PRC did not differ between the
      genotypes (nNOS(+/+) 743 +/- 115 10(-5) Goldblatt units; nNOS(-/-) 822 +/- 63 10(
      5) Goldblatt units), but during the low sodium diet, nNOS(-/-) mice failed to
      increase PRC (nNOS(+/+) 2164 +/- 220 10(-5) Goldblatt units; nNOS(-/-) 907 +/-
      101 10(-5) Goldblatt units) and renal renin mRNA. On the low sodium diet, nNOS(-/
      ) mice also showed increased urine flow rate and osmolar excretion, observations
      not made during a high sodium diet. CONCLUSIONS: Our results show that nNOS is
      necessary for stimulation of renin in response to sodium restriction.
      Furthermore, nNOS(-/-) mice are normotensive, and their blood pressure responds
      normally to an increased dietary sodium intake, indicating that nNOS deficiency
      does not cause salt-sensitive hypertension.

PMID- 18091754
TI  - Regional association-based fine-mapping for sodium-lithium countertransport on
      chromosome 10.
AB  - BACKGROUND: Increased erythrocyte sodium-lithium countertransport (SLC) has been
      observed in patients with essential hypertension. Consistent evidence of genetic
      linkage was shown for SLC on chromosome 10, and a region of interest was
      localized between 26 and 56 Mb. METHODS: This study surveyed single nucleotide
      polymorphisms (SNPs) in 54 genes that reside in the region of interest, and
      investigated their association with SLC and blood pressure. These SNPs were
      genotyped in 1,133 non-Hispanic white individuals from 255 pedigrees comprising
      the second phase of the Rochester Family Heart Study. The variance-components
      based genetics software package SOLAR was used for evaluating whether an SNP
      contributed to a significant fraction of the trait heritability. RESULTS: Of the
      77 SNPs surveyed in this study across the region of interest, four SNPs were
      associated with SLC (P < 0.04), five SNPs were associated with blood pressure (P
      < 0.04), and two SNPs in mannose-binding lectin 2 (MBL2) were associated with
      both phenotypes. In general, the pairwise linkage disequilibrium among the
      genotyped SNPs was low. CONCLUSIONS: This fine-mapping survey of genetic
      variation in a linkage region of interest provides overall support for
      association-mapping for SLC on chromosome 10. Genes significantly associated with
      systolic blood pressure and/or SLC in these families will be prioritized for
      future studies.

PMID- 18091755
TI  - Overexpression of mitochondrial Hsp70/Hsp75 protects astrocytes against ischemic
      injury in vitro.
AB  - Mitochondrial heat shock protein 70 (mtHsp70/Hsp75/Grp75/mortalin/TRAP-1/PBP74)
      is an essential mitochondrial chaperone and a member of the heat shock protein 70
      (HSP70) family. Although many studies have shown the protective properties of
      overexpression of the cytosolic inducible member of the HSP70 family, Hsp72, few
      studies have investigated the protective potential of Hsp75 against ischemic
      injury. Mitochondria are one of the primary targets of ischemic injury in
      astrocytes. In this study, we analyzed the effects of Hsp75 overexpression on
      cellular levels of reactive oxygen species (ROS), mitochondrial membrane
      potential, ATP levels, and viability during the ischemia-like conditions of
      oxygen-glucose deprivation (OGD) or glucose deprivation (GD) in primary
      astrocytic cultures. We show that Hsp75 overexpression decreases ROS production
      and preserves mitochondrial membrane potential during GD, and preserves ATP
      levels and cell viability during OGD. These findings indicate that Hsp75 can
      provide protection against ischemia-like in vitro injury and suggest that it
      should be further studied as a potential candidate for protection against
      ischemic injury.

PMID- 18091756
TI  - Verification of enhancement of the CSF space, not parenchyma, in acute stroke
      patients with early blood-brain barrier disruption.
AB  - Enhancement on post-contrast fluid-attenuated inversion recovery (FLAIR) images
      after acute stroke has been attributed to early blood-brain barrier disruption.
      Using an estimate of parenchymal volume fraction and the apparent diffusion
      coefficient (ADC), we investigated the relative contributions of cerebral spinal
      fluid (CSF) and parenchyma to enhancement seen on postcontrast FLAIR. Enhancing
      regions were found to have low parenchymal volume fractions and high ADC values,
      approaching that of pure CSF. These findings suggest that contrast enhancement on
      FLAIR occurs predominately in the CSF space, not parenchyma.

PMID- 18091757
TI  - Cerebral blood flow heterogeneity in preterm sheep: lack of physiologic support
      for vascular boundary zones in fetal cerebral white matter.
AB  - Periventricular white matter (PVWM) injury is the leading cause of neurologic
      disability in survivors of prematurity. To address the role of ischemia in PVWM
      and cerebral cortical injury, we hypothesized that immaturity of spatially distal
      vascular 'end zones' or 'border zones' predisposes PVWM to greater decreases in
      cerebral blood flow (CBF) than more proximal structures. We quantified regional
      CBF with fluorescently labeled microspheres in 0.65 gestation fetal sheep in
      histopathologically defined three-dimensional regions by post hoc digital
      dissection and coregistration algorithms. Basal flow in PVWM was significantly
      lower than in gyral white matter and cortex, but was equivalent in superficial,
      middle, and deep PVWM. Absolute and relative CBF (expressed as percentage of
      basal) did not differ significantly during ischemia or reperfusion between PVWM,
      gyral white matter, or cortex. Moreover, CBF during ischemia-reperfusion was
      equivalent in three adjacent PVWM levels and was not consistent with the
      magnitude of severity of PVWM injury, defined by TUNEL (terminal
      deoxynucleotidyltransferase-mediated dUPT nick end labeling) staining. However,
      the magnitude of ischemia was predicted by the severity of discrete cortical
      lesions. Hence, unlike cerebral cortex, unique CBF disturbances did not account
      for the distribution of PVWM injury. Previously defined cellular maturational
      factors, thus, appear to have a greater influence on PVWM vulnerability to
      ischemic injury than the presence of immature vascular boundary zones.

PMID- 18091759
TI  - Innovative early development regulatory approaches: expIND, expCTA, microdosing.
AB  - The Food and Drug Administration (FDA) Critical Path Initiative as well as the
      European Medicines Agency Road Map to 2010 (ref. 2) call for opportunities for
      more efficient drug development. One of the initiatives that has emerged in this
      context is the elaboration through guidance of exploratory investigational new
      drugs (INDs)/clinical trial applications (CTAs). This article reviews the history
      of these emerging guidances as well as the experience to date in their use by the
      industry.

PMID- 18091758
TI  - Monoamine oxidase inhibition for tobacco pharmacotherapy.
AB  - Tobacco addiction is the most significant preventable cause of morbidity and
      mortality in the Western world, with >430,000 deaths annually from tobacco
      related diseases being reported in the United States. Although effective
      treatments are available for cessation of smoking (e.g., nicotine replacement
      therapies, sustained-release bupropion and varenicline), they do not work for all
      smokers. Therefore the development of more effective medications for treating
      tobacco dependence, based on novel mechanisms, is a high priority. This article
      reviews the links between smoking and monoamine oxidase (MAO) inhibition, which
      could lead to the development of novel pharmacotherapies to treat tobacco
      dependence.

PMID- 18091760
TI  - High-risk molecules or insufficient scientific data?
AB  - When I was invited to author an ethics policy piece on the "approach to high-risk
      molecules" as a contribution to the theme of "Innovation in Drug Development" of
      this Clinical Pharmacology & Therapeutics issue, I thought there was a need to
      evaluate whether questioning the transition from preclinical to clinical
      development after the TGN 1412 serious adverse event may freeze the development
      of innovating tools in drug development.

PMID- 18091761
TI  - Declining public health burden of digoxin toxicity from 1991 to 2004.
AB  - We hypothesized that digoxin toxicity has declined in recent years, and that the
      decline is accompanied by reductions in overall utilization and dose. To analyze
      trends in digoxin toxicity and utilization from 1991 to 2004, we used surveys
      from the National Center for Health Statistics and Medicaid data in the United
      States and The Health Improvement Network (THIN) database in the United Kingdom.
      There was a significant decline in digoxin toxicity hospitalizations in the
      United States and a decline in ambulatory digoxin toxicity in the United Kingdom.
      The study demonstrated a reduction in the use of digoxin in the United States,
      but found no change in digoxin use in the United Kingdom. Finally, the number of
      prescriptions written for at least 250 microg decreased in the United States and
      the United Kingdom. The public health burden of digoxin toxicity declined
      dramatically from 1991 to 2004 in the United Kingdom and the United States.

PMID- 18091762
TI  - A prototypical process for creating evidentiary standards for biomarkers and
      diagnostics.
AB  - A framework for developing evidentiary standards for qualification of biomarkers
      is a key need identified in the Food and Drug Administration's Critical Path
      Initiative. This article describes a systematic framework that was developed by
      Pharmaceutical Research and Manufacturers of America (PhRMA) committees and
      tested at a workshop in collaboration with the Food and Drug Administration and
      academia. With some necessary refinements, this could be applied to create an
      appropriately individualized evidentiary standard for any biomarker purpose.

PMID- 18091763
TI  - Advances in the treatment of breast cancer.
AB  - Breast cancer is the most commonly diagnosed cancer in American women and is the
      second leading cause of cancer-related deaths in this population. This review
      highlights how the use of a multidisciplinary approach to the management of
      diseases of the breast and the introduction of novel systemic therapies have
      improved the quality of life and survival in patients with breast cancer.

PMID- 18091765
TI  - Dietary patterns and vitamin B(12) status of migrant Indian preadolescent girls.
AB  - BACKGROUND: Inter-generational dietary patterns are implicated in the development
      of adult disease and have a critical role in cell division, growth and
      development. OBJECTIVE: The assessment of B(12) status in six meat-eating (ME)
      and six non-meat-eating (NME) 9-11 years old, Tanner stage 1, migrant Indian
      girls. DESIGN: B(12) status was assessed by haematology, fasting B(12), folate,
      methyl malonic acid (MMA) and 7-day-diet-diary analysis. RESULTS: Red cell and
      iron measurements were within reference ranges for all girls. Reported B(12)
      intake correlated with serum B(12) (r=0.74, P=0.006). Serum B(12) was lower in
      NME girls compared with ME girls (232+/-95 vs 543+/-201 pmol l(-1), P=0.01). Two
      NME girls were deficient in vitamin B(12) (B(12)<170 pmol l(-1), MMA>0.26
      micromol l(-1)). Overall serum B(12) was low (388+/-221 pmol l(-1)) and serum
      folate intake high (27+/-8 pmol l(-1); 342+/-269 microg day(-1)). CONCLUSIONS:
      Asymptomatic B(12) deficiency is present in NME migrant Indian preadolescents in
      the presence of high folate. Supplementation with B(12) in this group may be
      necessary to improve future health outcomes.

PMID- 18091766
TI  - Relationship between long-chain polyunsaturated fatty acids at birth and motor
      function at 7 years of age.
AB  - BACKGROUND/OBJECTIVES: Long-chain polyunsaturated fatty acids (LCPUFA) rapidly
      accumulate in the central nervous system (CNS) during the perinatal CNS growth
      spurt. This particularly concerns arachidonic acid (AA: 20:4n-6) and
      docosahexaenoic acid (DHA: 22:6n-3), which are thought to play important roles in
      CNS development and function. The aim of this study was to investigate the
      relation between motor function at 7 years of age and the levels of AA and DHA in
      umbilical venous plasma phospholipids, representing the prenatal availability of
      these fatty acids, and in plasma phospholipids sampled at age 7 years.
      SUBJECTS/METHODS: Motor function was assessed both quantitatively (the ability to
      perform a movement) and qualitatively (how the movement is performed) with the
      Maastricht Motor Test (MMT) in 306 children, born at term, at 7 years of age as
      part of a follow-up study. RESULTS: Backward stepwise multiple regression
      analyses revealed a significant, positive relation between umbilical plasma DHA
      concentrations (but not plasma DHA levels at 7 years) and the MMT total and
      quality score, corrected for the covariables gender, cognitive performance,
      gestational age and age at measurement (partial beta=0.13, P=0.01 and 0.14,
      P=0.01, respectively). The contributions of DHA and AA (both at birth and at 7
      years of age) to quantitative movement scores were not significant. CONCLUSIONS:
      Our results suggest that prenatal DHA availability, which can be influenced by
      maternal dietary DHA intake during pregnancy, can have an effect on quality of
      movement in later life.

PMID- 18091767
TI  - Dietary glycemic index, dietary glycemic load and mortality among men with
      established cardiovascular disease.
AB  - BACKGROUND/OBJECTIVES: In men with established cardiovascular disease, the effect
      of diets with high glycemic index (GI) and glycemic load (GL) is unknown. We
      tested the hypothesis that diets with higher GI and GL are associated with
      increased mortality in men with established cardiovascular disease.
      SUBJECTS/METHODS: We measured dietary GI and GL using food-frequency
      questionnaires in 4617 men, 45-79 years old, with a history of cardiovascular
      disease. The men were followed for cardiovascular mortality (6-year follow-up,
      608 cases) and all-cause mortality (8-year follow-up, 1303 cases) using the
      Swedish cause-of-death and death registers. We used Cox models with age as the
      timescale and adjusted for body mass index, physical activity, history of
      hypertension and diabetes, family history of myocardial infarction, aspirin use,
      cigarette smoking and dietary factors to estimate incidence rate ratios (RRs).
      RESULTS: Comparing top to bottom quartiles of dietary GI, the RR for
      cardiovascular mortality was 0.86 (95% confidence interval (CI) 0.67-1.10, P for
      linear trend=0.21), and the RR for all-cause mortality was 1.00 (95% CI 0.85
      1.19, P for linear trend=0.87). Compared to quartile 1, the RR for men with
      dietary GL in quartile 4 was 1.02 (95% CI 0.70-1.49, P for linear trend=0.81) for
      cardiovascular and 1.15 (95% CI 0.89-1.49, P for linear trend=0.20) for all-cause
      mortality. CONCLUSIONS: In this population of men with prior cardiovascular
      disease, dietary GI and GL were not associated with cardiovascular or all-cause
      mortality.

PMID- 18091769
TI  - Linkage disequilibrium analysis in the genetically isolated Norfolk Island
      population.
AB  - Norfolk Island is a human genetic isolate, possessing unique population
      characteristics that could be utilized for complex disease gene localization. Our
      intention was to evaluate the extent and strength of linkage disequilibrium (LD)
      in the Norfolk isolate by investigating markers within Xq13.3 and the NOS2A gene
      encoding the inducible nitric oxide synthase. A total of six microsatellite
      markers spanning approximately 11 Mb were assessed on chromosome Xq13.3 in a
      group of 56 men from Norfolk Island. Additionally, three single nucleotide
      polymorphisms (SNPs) localizing to the NOS2A gene were analyzed in a subset of
      the complex Norfolk pedigree. With the exception of two of the marker pairs, one
      of which is the most distantly spaced marker, all the Xq13.3 marker pairs were
      found to be in significant LD indicating that LD extends up to 9.5-11.5 Mb in the
      Norfolk Island population. Also, all SNPs studied showed significant LD in both
      Norfolk Islanders and Australian Caucasians, with two of the marker pairs in
      complete LD in the Norfolk population only. The Norfolk Island study population
      possesses a unique set of characteristics including founder effect, geographical
      isolation, exhaustive genealogical information and phenotypic data of use to
      cardiovascular disease risk traits. With LD extending up to 9.5-11 Mb, the
      Norfolk isolate should be a powerful resource for the localization of complex
      disease genes.

PMID- 18091768
TI  - Multiple micronutrient fortification of salt.
AB  - BACKGROUND/OBJECTIVE: To develop a salt fortified with multiple micronutrients,
      to test its stability during storage and cooking, and to assess its efficacy in
      improving the micronutrient status and the health of schoolchildren.
      SUBJECT/METHODS: A salt fortified with multiple micronutrients was developed
      containing chelated ferrous sulfate and microencapsulated vitamins A, B1, B2, B6,
      B12, folic acid, niacin, calcium pantothenate and iodine. Its stability during 20
      min of cooking and 6 months of storage was determined. Thereafter, the efficacy
      of the salt was assessed in 5- to 15-year-old schoolchildren in Chennai, India.
      For the experimental group (N=119), the food in the school kitchen was cooked
      with fortified salt for a period of 1 year. The control group (N=126) consisted
      of day scholars who did not eat at the school. Hemoglobin, red blood cell count,
      hematocrit, serum vitamin A and urinary iodine were measured at baseline and at
      the end of the study after 1 year. RESULTS: All micronutrients were stable during
      cooking and storage. Over the study period, there was a significant improvement
      (P<0.05) in hemoglobin, red cell count, urinary iodine and serum vitamin A in the
      experimental group, while there was a significant drop (P<0.05) in hemoglobin,
      hematocrit, red cell count and urinary iodine in the control group. In the
      experimental group, there was a mean increase of 0.55 g/dl in hemoglobin, 0.001
      l/l in hematocrit, 0.470 million/mm(3) in red cell count, 212 microg/l in urinary
      iodine and 5.6 microg/dl in serum vitamin A. CONCLUSION: The study shows that the
      salt fortified with multiple micronutrients is stable during cooking and storage
      and effective in combating multiple micronutrient deficiencies.

PMID- 18091770
TI  - Genetic variation in the invasive process of Bursaphelenchus xylophilus
      (Aphelenchida: Aphelenchoididae) and its possible spread routes in China.
AB  - Pinewood nematode (Bursaphelenchus xylophilus) is an invasive species that causes
      a destructive forest disease-pine wilt disease. This disease has been prevalent
      in some countries in Asia since the 1970s. An amplified fragment length
      polymorphism survey was used to compare the genetic variation of native and
      invasive nematode populations in China and to examine the changes in genetic
      diversity during the invasion process. The genetic diversity of Chinese
      populations was slightly higher than that of American populations. Analysis of
      groups sampled from different invasive stages in China, showed that no obvious
      change in genetic diversity. Hence, genetic drift and founder effects are not
      obvious in the invasion process. Phylogenetic analysis showed that Chinese
      pinewood nematode populations were closer to Japanese populations than to
      American populations. On the basis of the genetic relationships among samples,
      two major invasion pathways in China are suggested. One is from Guangdong to
      Anhui and Zhejiang, and the other is from Guangdong to Jiangsu and then from
      Jiangsu to Hubei, Guizhong and Congqing. The results imply that it is important
      to reinforce both domestic and international quarantine to control the spread of
      pinewood nematode.

PMID- 18091771
TI  - Differential barrier strength and allele frequencies in hybrid zones maintained
      by sex-biased hybrid incompatibilities.
AB  - In animals, hybrid sterility and inviability between closely related species
      often affect only the heterogametic sex (XY). This widespread phenomenon, known
      as Haldane's rule, is an early speciation event found across broad taxa, but the
      role of heterogametic hybrid incompatibilities, as opposed to homogametic ones,
      as a barrier in a speciation process remains obscure. It has been hypothesized
      that heterogametic incompatibility may be a more efficient mechanism in driving
      speciation. The population dynamics after (rather than before) the occurrence of
      sex-biased incompatibilities may account for Haldane's rule. In this study, a
      recursion model of hybrid zones was developed to investigate the differences
      between heterogametic and homogametic incompatibilities. The selection strengths
      and selection patterns of sex chromosome-linked, two-locus Bateson-Dobzhansky
      Muller (BDM) genetic incompatibilities were examined. It is noted that a sex
      biased hybrid incompatibility in a hybrid zone confers asymmetric and uneven
      impedance to gene flow. The clines of different loci in such a hybrid zone
      displayed diverse differentiation in their width, steepness and asymmetry.
      Alleles involved in the incompatibility face much stronger resistance to cross a
      hybrid zone. Different sex-biased BDM incompatibilities also affect the flow of
      neutral alleles differently. Compared to a homogametic one, heterogametic
      incompatibility is a weaker but more asymmetric barrier. These unique patterns of
      gene flow may explain uneven divergence among different genomic regions during
      speciation between some closely related species.

PMID- 18091773
TI  - Quasi-phase-matched second-harmonic generation by use of a total-internal
      reflection phase shift in gallium arsenide and zinc selenide plates.
AB  - We fabricated a novel quasi-phase-matched frequency converter, using a zigzag
      optical beam path in a thin, polished parallel plate. Second-harmonic generation
      experiments demonstrated angle-tuned output at 4.6 to 5.3mum in GaAs and 1.7 to
      2.0mum in ZnSe crystals when pulsed infrared laser sources were used.

PMID- 18091774
TI  - Dispersion-managed breathers with average normal dispersion.
AB  - Analytic and numerical evidence is presented that demonstrates that a dispersion
      managed breather can be supported in an optical fiber even when the average
      dispersion is in the normal regime. This nonlinear behavior, which is contrary to
      guiding-center theory, is shown to originate from the reversible dynamics
      associated with the strong quadratic chirp that is generated in both the
      anomalous and the normal dispersion regimes.

PMID- 18091772
TI  - Provision and quality assurance of preimplantation genetic diagnosis in Europe.
AB  - Preimplantation genetic diagnosis (PGD) is now well established and provided in
      many European countries. However, regulations, professional standards and
      accreditation requirements can differ notably. Furthermore, no comprehensive
      independent data exist either about practice and provision in Europe or about the
      quality assurance practices and procedures designed to optimize the quality of
      the results. Consequently, a study was launched to obtain knowledge, currently
      lacking, of the provision and quality assurance of PGD services and cross-border
      activities in Europe. An online questionnaire was developed and sent to PGD
      providers, and expert opinions were obtained through interviews with
      professionals in specific countries. Information was gathered from 53 centres
      offering PGD in 17 European countries. There is a diverse array of tests
      available, with a trend for custom-made services. Although half of the centres
      have a designated quality manager, just 33% have achieved or are preparing for
      accreditation or certification. About 66% of the centres responded that they did
      not participate in external quality assessment, a problem exacerbated by the lack
      of existing PGD-specific schemes. Approximately 19% of the centres do not keep
      data on accuracy and 9% do not even follow up until birth. PGD is an expanding
      activity with an increasing international flow that accounts for approximately
      one-third of the activity reported. The survey highlights a significant need for
      improvement in quality assurance in PGD centres. On the positive side, important
      improvements in the quality management of these services are expected with the
      European Tissue Directive entering into force.

PMID- 18091775
TI  - Electromagnetic energy transport via linear chains of silver nanoparticles.
AB  - We propose the idea of a subwavelength-sized light guide represented by a linear
      chain of spherical metal nanoparticles in which light is transmitted by
      electrodynamic interparticle coupling. The light-transport properties of this
      system are investigated by use of model calculations based on generalized Mie
      theory. Considering Ag particles of 50-nm diameter, we find optimum guiding
      conditions for an interparticle spacing of 25 nm, and a corresponding 1/e signal
      damping length of 900 nm is evaluated. The proposed principle of optical energy
      transport may be useful for subwavelength transmission lines within integrated
      optics circuits and for near-field optical microscopy.

PMID- 18091776
TI  - Induced transient gratings as a probe of the early-stage kinetics of phase
      separating liquid mixtures.
AB  - Because of the large number of nucleated domains and the polydispersity of the
      droplet distribution, the early-stage kinetics of a first-order phase transition
      remains difficult to explore. We investigate this issue by using laser-induced
      concentration variations to drive a transition locally in a liquid mixture with
      two intersecting pump beams whose interference pattern traps the nucleated
      droplets on the optical fringes. The time-resolved reflectivity of a third probe
      wave on the induced droplet grating allows us to characterize the droplet growth
      at its early stage, which illustrates the efficiency of transient grating methods
      in quantifying the kinetics of out-of-equilibrium processes.

PMID- 18091777
TI  - Pulse delay at diffractive structures under resonance conditions.
AB  - An optical pulse incident upon a diffractive structure under resonance conditions
      may undergo a temporal delay. The effect is demonstrated with a pulse of Gaussian
      profile at two geometries: a waveguide grating and a single-mode waveguide. It is
      shown that the order of magnitude of the delay can be controlled by the
      parameters of the structures.

PMID- 18091778
TI  - Spectral changes produced by static scattering on a system of particles.
AB  - A formula of considerable generality is derived for the spectrum of light
      produced by static scattering of polychromatic light on a system of particles. It
      applies to deterministic as well as to random distributions of monodispersed or
      polydispersed particles. We illustrate it by examples. It is suggested that
      spectral changes produced by scattering could be used for determining the
      structure of some scattering systems.

PMID- 18091780
TI  - Apparent superresolution in near-field optical imaging of periodic gratings.
AB  - A superresolution phenomenon in images of diffraction gratings obtained with a
      near-field optical microscope probe positioned at distances of the order of
      1>mu;m from the surface was recently reported [Appl. Opt. 33, 876 (1994)]. This
      experiment was interpreted in terms of evanescent waves observed in the far
      field. We show that the effect observed in that experiment is a very well known
      far-field optical phenomenon called the Talbot effect. The existence of self
      imaging Talbot planes for gratings with periods of the order of a few micrometers
      appears promising for many practical applications.

PMID- 18091779
TI  - Binary subwavelength diffractive-lens design.
AB  - We present a procedure for the design of binary diffractive lenses with pulse
      width-modulated subwavelength features. The procedure is based on the combination
      of two approximate theories, effective medium theory and scalar diffraction
      theory, and accounts for limitations on feature size and etch depth imposed by
      fabrication. A design example is presented.

PMID- 18091781
TI  - Compact low-threshold Q-switched intracavity optical parametric oscillator.
AB  - We report a singly resonant pulsed intracavity KTiOPO>(4) optical parametric
      oscillator that uses a semi-monolithic microchip laser design. The compact (50-mm
      long), low-threshold (1.3-W) cavity uses a novel quadrupole deflector Q switch to
      give 4-microJ pulses at 1.064 microm and 0.4-microJ signal pulses of 5.6-ns
      duration at 1.53 microm with a repetition frequency of 5 kHz when it is pumped
      with a 2-W laser diode. The signal pulses are diffraction limited and single
      frequency.

PMID- 18091782
TI  - Self-similar core and oscillatory tails of a path-averaged chirped dispersion
      managed optical pulse.
AB  - We describe the breathing dynamics of the self-similar core and the oscillating
      tails of a dispersion-managed (DM) soliton. The path-averaged propagation
      equation governing the shape of the DM soliton in an arbitrary dispersion map is
      derived. The developed theory correctly predicts the locations of the dips in the
      tails of the DM soliton. A general solution of the propagation equation is
      presented in terms of chirped Gauss-Hermite orthogonal functions.

PMID- 18091783
TI  - Soliton collisions with wavelength-division multiplexed systems with strong
      dispersion management.
AB  - We investigate collisions between solitons in a lossless two-channel wavelength
      division multiplexed system with strong dispersion management. Numerical results
      show that the net frequency shift that is due to interchannel collisions is at
      least 1 order of magnitude smaller than predicted by adiabatic theories. A
      modified theoretical analysis is presented and shown to be in good agreement with
      the numerical results.

PMID- 18091784
TI  - Electrostrictive cross-phase modulation of periodic pulse trains in optical
      fibers.
AB  - Electrostriction-induced cross-phase modulation between subsequent bits of a
      nonreturn-to-zero pulse train in optical fibers leads to nonlinear frequency
      shifts of opposite sign for the 1's and the 0's. Direct experimental measurements
      of the electrostrictive and Kerr-induced nonlinear phase shift across the bit
      profiles agree well with the theoretical modeling.

PMID- 18091786
TI  - High-power diode-bar end-pumped Nd:YLF laser at 1.053 microm.
AB  - We describe efficient cw operation of a Nd:YLF laser end pumped by two beam
      shaped 20-W diode bars on the 1.053-microm transition. Fundamental transverse
      mode operation with output power of 11.1 W for ~29.5 W of incident pump power was
      demonstrated. In Q-switched operation 8.4 W of average power at a pulse
      repetition frequency of 40 kHz and ~2.6-mJ pulse energy at a pulse repetition
      frequency of 1 kHz were achieved.

PMID- 18091785
TI  - Timing jitter of solitons compressed in dispersion-decreasing fibers.
AB  - It is shown that timing jitter owing to the Gordon-Haus (G-H) effect of solitons
      that are compressed adiabatically in dispersion-decreasing fibers (DDF's) is
      approximately determined by total dispersion and initial conditions, which are
      independent of compression dynamics. As a result the established theory for G-H
      jitter is still applicable. Timing jitter near the levels predicted by theory is
      observed in pulses from a regeneratively mode-locked fiber laser compressed in a
      DDF.

PMID- 18091787
TI  - Long-wavelength (lambda approximately 8-11.5 microm) semiconductor lasers with
      waveguides based on surface plasmons.
AB  - Laser waveguides based on surface plasmons at a metal-semiconductor interface
      have been demonstrated by use of quantum cascade (QC) lasers emitting in the 8
      11.5-microm wavelength range. The guided modes are transverse magnetic polarized
      surface waves that propagate at the metal (Pd or Ti-Au)-semiconductor interface
      between the laser top contact and the active region without the necessity for
      waveguide cladding layers. The resultant structure has the advantages of a strong
      decrease in the total layer thickness and a higher confinement factor of the
      laser-active region compared with those of a conventional layered semiconductor
      waveguide, and strong coupling to the active material, which could be used in
      devices such as distributed-feedback lasers. These advantages have to be traded
      against the disadvantage of increased absorption losses. A peak output power
      exceeding 25 mW at 90 K and a maximum operating temperature of 150 K were
      measured for a QC laser with an emission wavelength lambda approximately 8 microm
      . At lambda approximately 11.5 microm the peak power levels are several
      milliwatts and the maximum operating temperature is 110 K.

PMID- 18091788
TI  - Low-frequency fluctuation induced by injection-current modulation in
      semiconductor lasers with optical feedback.
AB  - Low-frequency fluctuations in semiconductor lasers with optical feedback are
      investigated when high-frequency modulation is applied to an injection current.
      Synchronization of the laser output power with the modulation within +/-3 MHz
      centered at the frequency corresponding to the external cavity mode was observed.
      However, for modulation of the detuned frequency from the external cavity mode,
      low-frequency fluctuations were induced in the laser output power, and these
      fluctuations were observed within a range of modulation of approximately +/-100
      MHz at the center frequency of the external cavity mode.

PMID- 18091789
TI  - Optical implementation of a constant-time multicomparand bit-parallel magnitude
      comparison algorithm using wavelength- and polarization-division multiplexing
      with application to parallel database processing.
AB  - We present a word- and bit-parallel magnitude-comparison architecture that
      permits multiple comparands to be compared with multiple relations in constant
      time. The proposed magnitude-comparison algorithm uses a novel polarization and
      wavelength-encoding scheme to achieve a fast, scalable realization. Distinctive
      features of the proposed architecture include (1) the use of a multiple
      wavelength encoding scheme to increase processing parallelism and (2) multiple
      comparand word- and bit-parallel comparison with an execution time that is
      independent of the data or word size.

PMID- 18091790
TI  - Demonstration of supercontinuum generation in a long-cavity fiber ring laser.
AB  - We demonstrate generation of supercontinuum pulses directly from a passively mode
      locked long-cavity fiber ring laser. The laser output exhibited a blueshifted
      spectrum extending from 1350 to 1550 nm with an average output power greater than
      60 mW.

PMID- 18091791
TI  - How to make femtosecond pulses overlap.
AB  - Normally, femtosecond light pulses that cross at a nonzero angle overlap over
      only a small region in space. This limitation can be overcome by the use of
      diffraction orders of a grating. We consider an arrangement in which, on
      diffraction of a femtosecond pulse by a grating, two beams that correspond to the
      first-order diffraction maxima are recombined at the image plane by a system of
      two confocal lenses. In this arrangement the beams overlap over the their full
      aperture, with the short duration of the pulses being preserved. We demonstrate
      the use of this setup as a simple autocorrelator and discuss a possible
      application to time-resolved vibrational spectroscopy.

PMID- 18091792
TI  - Time-resolved nonlinear refraction in femtosecond laser gain media.
AB  - We present time-resolved measurements of the electronic and the nuclear
      contributions to the third-order nonlinearities of Ti:sapphire and Cr:LiSGaF. The
      results suggest that nonlinear refraction in Ti:sapphire is resonantly enhanced
      relative to that of undoped sapphire. The implications of the nonlinear responses
      for short-pulse formation are discussed.

PMID- 18091793
TI  - Generation of 0.66-TW pulses at 1 kHz by a Ti:sapphire laser.
AB  - A 1-kHz, 0.66-TW Ti:sapphire laser has been developed. We obtained 21-fs, 14-mJ
      pulses with an extraction efficiency of 32% in the final amplifier. The
      dispersion through the system was successfully compensated for by insertion of a
      pair of prisms in a regenerative amplifier. The pulses were characterized by
      frequency-resolved optical gating and were in good agreement with dispersion
      calculated by three-dimensional ray tracing.

PMID- 18091794
TI  - Accuracy of optical frequency comb generators and optical frequency interval
      divider chains.
AB  - We compared two methods for measuring large optical frequency differences: an
      optical frequency comb generator, which creates a large number of sidebands from
      a single-mode laser through electro-optic modulation, and an optical frequency
      interval divider chain, which divides a frequency gap successively by two until
      it becomes accessible to a radio-frequency counter. By locking two diode lasers
      to two modulation sidebands of a comb generator, ~1 THz apart, and measuring this
      interval with a chain of four phase-locked interval dividers, we demonstrate for
      the first time to our knowledge the accuracy of both techniques within an
      experimental limit of 6.8 x 10(-15).

PMID- 18091795
TI  - Amplitude-squeezed solitons from an asymmetric fiber interferometer.
AB  - We experimentally demonstrate a new scheme for generating amplitude-squeezed
      solitons in an asymmetric fiber Sagnac loop. We measure by direct detection what
      is to our knowledge a record reduction of 5.7+/-0.1 dB (73%) and, with
      corrections for linear losses, 6.2+/-0.1 dB (76%) in the photon-number
      fluctuations below the shot-noise level. The same scheme is also shown to
      generate significant classical noise reduction and is limited by Raman effects in
      fiber.

PMID- 18091796
TI  - Investigation of the photon statistics of parametric fluorescence in a traveling
      wave parametric amplifier by means of self-homodyne tomography.
AB  - Photon-number distributions for parametric fluorescence from a nondegenerate
      optical parametric amplifier are measured with a novel self-homodyne technique.
      These distributions exhibit the thermal-state character predicted by theory.
      However, a difference between the fluorescence gain and the signal gain of the
      parametric amplifier is observed. We attribute this difference to a change in the
      signal-beam profile during the traveling-wave pulsed amplification process.

PMID- 18091797
TI  - High-resolution (Doppler-limited) spectroscopy using quantum-cascade distributed
      feedback lasers.
AB  - Lasing characteristics were evaluated for distributed-feedback quantum-cascade
      (QC) lasers operating in a continuous mode at cryogenic temperatures. These tests
      were performed to determine the QC lasers' suitability for use in high-resolution
      spectroscopic applications, including Doppler-limited molecular absorption and
      pressure-limited lidar applications. By use of a rapid-scan technique, direct
      absorbance measurements of nitric oxide (NO) and ammonia (NH>(3)) were performed
      with several QC lasers, operating at either 5.2 or 8.5 microm. Results include
      time-averaged linewidths of better than 40 MHz and long-term laser frequency
      reproducibility, even after numerous temperature cycles, of 80 MHz or better.
      Tuning rates of 2.5 cm(-1) in 0.6 ms can be easily achieved. Noise-equivalent
      absorbance of 3 x 10(-6) was also obtained without optimizing the optical
      arrangement.

PMID- 18091798
TI  - Two-photon apodization in lithium niobate.
AB  - We demonstrate a novel apodization technique for holographic data storage using
      two-photon recording in stoichiometric lithium niobate. The gating light
      intensity profile is used to achieve grating apodization inside the bulk of the
      crystal during recording in the transmission geometry. Experimental Bragg
      selectivity curves and theoretical fits indicate a >20-dB drop in multiplexing
      cross talk.

PMID- 18091799
TI  - Effects of drawing tension on the photosensitivity of Sn-Ge- and B-Ge-codoped
      core fibers.
AB  - The influence of drawing tension on the formation of Bragg gratings in B-Ge- and
      Sn-Ge-codoped core fibers is investigated by transmission and stress
      measurements. With increasing drawing tension, the axial stress is reduced in the
      B-Ge-codoped core but increased in the Sn-Ge-codoped core. A higher drawing
      tension leads to a photosensitivity enhancement and an increase of the core
      stress during the grating formation in B-Ge-codoped fibers. For Sn-Ge-codoped
      fibers, increased drawing tension results in an UV-induced stress decrease
      accompanied by a reduction of the photosensitivity. The results are discussed on
      the basis of an UV-induced compaction of the core network.

PMID- 18091800
TI  - Thermally fixed reflection gratings for infrared light in LiNbO(3):Ti:Fe channel
      waveguides.
AB  - We present a narrow-bandwidth interference filter in an optical monomode
      LiNbO>(3):Ti:Fe channel waveguide operating in the infrared wavelength region
      around lambda = 1.55 microm . The filter consists of a thermally fixed refractive
      index Bragg grating recorded with visible green light by use of a holographic
      technique. In a first approach we measure a reflectivity for the infrared light
      of 60% and a linewidth (FWHM) of 0.11 nm.

PMID- 18091801
TI  - One-step two-dimensional rainbow-holographic technique with a nonlaser light
      source: errata.
AB  - On p. 1055 of Ref. 1, just above Eq. (1), the wavelength of the argon-ion laser
      should be 458 nm, not 4.58 nm. On p. 1056, in the third-to-last paragraph, the
      spectrum of the InGa lamp should be 320450 nm, not 3.24.5 nm.

PMID- 18091802
TI  - Annealing effect on ion-beam-sputtered titanium dioxide film.
AB  - We found that the extinction coefficient of ion-beam-sputtered titanium dioxide
      films first decreased with increasing annealing temperature then increased
      drastically when annealing temperature was increased above ~200 degrees C for 24
      h of annealing time. The decreasing extinction coefficient with annealing
      temperature was attributed to a reduction in absorption owing to oxidation of the
      film by annealing. The film structure remained amorphous to 200 degrees C
      annealing temperature. The drastic increase of extinction coefficients above ~200
      degrees C was associated with the appearance of an anatase polycrystalline
      structure and was attributed to scattering by the polycrystalline structure. With
      shorter annealing time the transition temperature from amorphous to
      polycrystalline anatase was higher. Guidance for reducing the optical loss of
      laser mirrors is proposed.

PMID- 18091803
TI  - Simultaneous measurements of three-dimensional reflectivity distributions in
      scattering media based on optical frequency-domain reflectometry.
AB  - A new type of tomography system based on optical frequency-domain reflectometry
      is presented. Using an area sensor, the system can simultaneously measure three
      dimensional reflectivity distributions in scattering media without the need for
      mechanical scanning. In preliminary experiments we demonstrate that a target
      (resolution chart) placed behind biological tissue can be imaged with high depth
      resolution (47 microm) for a short measurement time.

PMID- 18091804
TI  - Importance of the (nabla) D term in frequency-resolved optical diffusion imaging.
AB  - The effects of the approximation DD=0 that is often used in frequency-resolved
      optical diffusion imaging are examined. It is shown that this approximation can
      affect the performance of integral-equation-based approaches to optical diffusion
      imaging, such as the Born iterative method and the distorted Born iterative
      method. The approximation introduces errors into the calculation of data used in
      simulations, which can lead to misleading evaluations of reconstruction
      algorithms. Numerical calculations show the magnitude of these effects and the
      appearance of artifacts in reconstructed images when conventional inversion
      algorithms are applied to more accurately calculated data.

PMID- 18091805
TI  - Chaos mirror for free-space links.
AB  - We propose a novel reflector, called a chaos mirror, designed by use of the
      principles of chaotic reflection. A feature of the reflector is that it converts
      a one-dimensional spread of incident rays into a two-dimensional spread of
      reflected rays. This can be useful for making free-space optical beam links by
      sweeping a transmission beam in only one dimension.

PMID- 18091806
TI  - Nonlinear ellipsometric method for measuring second-order cascaded phase shift.
AB  - An ellipsometric method for measuring second-order cascaded phase shift is
      experimentally demonstrated in a KNbO(3) single crystal. We analyze the
      polarization state composed of the two orthogonal polarizations of the
      transmitted fundamental wave, one of which experiences intensity-dependent
      depletion and phase shift while the other does not. This method does not require
      a well-defined beam profile or interferometric stability.

PMID- 18091807
TI  - Tunable, visible phase conjugator with a saturable-amplifier polymer laser dye.
AB  - We present the first report to the best of our knowledge of highly efficient
      phase conjugation in a laser-pumped polymer-dye saturable amplifier. Phase
      conjugate reflectivity of as much as 210% at 560 nm has been obtained. Moreover,
      efficient reflectivity has been obtained in the broad wavelength region from 556
      to 567 nm.

PMID- 18091808
TI  - Giant momentary readout produced by switching electric fields during two-wave
      mixing in sillenites.
AB  - We show theoretically and experimentally that switching an applied square-wave
      field produces strong and short pulses of the outgoing signal during two-wave
      mixing in sillenite crystals. These pulses originate from the strong effect of
      the field on the optical eigenmodes and can be used in new optical schemes based
      on time-separated recording and readout processes.

PMID- 18091809
TI  - Dynamic, electronically controlled angle steering of spatial solitons in AlGaAs
      slab waveguides.
AB  - We demonstrate experimentally that spatial solitons in AlGaAs slab waveguides can
      be deflected by an electronically induced prism. We also show that a weak signal
      beam can be guided and steered by the solitons, thus demonstrating the
      feasibility of a dynamically reconfigurable optical interconnect.

PMID- 18091810
TI  - High-efficiency blue generation by frequency doubling of femtosecond pulses in a
      thick nonlinear crystal.
AB  - We have demonstrated highly efficient frequency doubling of femtosecond pulses in
      a thick, noncritically phase-matched KNbO(3) crystal under conditions of large
      group-velocity mismatch. At low power we observed a slope efficiency of ~300% nJ
      (-1) for harmonic conversion, and at higher powers we generated 170 mW of second
      harmonic blue output for 300 mW of input light. Furthermore, we have shown that
      the focusing dependence for our conditions of large group-velocity mismatch is
      considerably different from that obtained for frequency doubling of continuous
      wave light. We have also demonstrated that one can tune the spectral width of the
      generated blue light by varying the focusing conditions.

PMID- 18091811
TI  - Observation of azimuthal modulational instability and formation of patterns of
      optical solitons in a quadratic nonlinear crystal.
AB  - We report what is believed to be the first experimental demonstration of the
      azimuthal self-breaking of intense beams containing a vortex phase dislocation
      into sets of optical spatial solitons in a quadratic nonlinear material. The
      observations were performed in a KTP crystal.

PMID- 18091812
TI  - UV-irradiation-induced structural transformation in phosphosilicate glass fiber.
AB  - The Raman spectra of phosphosilicate core (P(2)O(5)-SiO(2)) fibers were
      investigated. Significant changes in the spectra were observed after UV
      irradiation of the fibers. An interpretation of the photostructural changes
      confirmed by computer simulation of phosphorus-related centers is proposed.

PMID- 18091813
TI  - Influence of Raman effects in wavelength-division multiplexed soliton systems.
AB  - Taking into account the delayed Raman response, an expression for the collision
      induced frequency shift is derived. In a wavelength-division multiplexed soliton
      system, solitons undergo cross-frequency shifts owing to collisions, which leads
      to timing jitter for transmission systems with bit rates of more than 40 Gbits/s
      per channel.

PMID- 18091814
TI  - Effect of synchronous modulation on the soliton optical phase.
AB  - We show that soliton regeneration through synchronous modulation reduces both
      amplitude and optical phase noise in a squeezinglike fashion. However, control of
      optical phase noise is found not to be sufficient to permit error-free phase
      shift-keyed soliton transmission, as confirmed by numerical simulations.

PMID- 18091815
TI  - Influence of parametric four-wave mixing effects on stimulated Raman scattering
      in bimodal optical fibers.
AB  - We analyze stimulated Raman scattering in normally dispersive bimodal fibers
      under single-frequency pumping conditions. Experiments show that whenever the
      interacting nonlinear waves propagate in the LP(01) and LP(11) modes, a
      parametric four-wave mixing enters unavoidably into play in the wave-coupling
      behavior, which causes qualitatively different phenomena compared with the
      ordinary process of Raman scattering, such as the parametric suppression of the
      first-order Raman Stokes radiation.

PMID- 18091816
TI  - Multiwavelength picosecond frequency-shifted feedback laser with pulse control by
      a shaped-gain fiber amplifier.
AB  - Stable generation of multiwavelength picosecond pulses by a frequency-shifted
      laser is demonstrated. Pulses are reliably trapped by gain variations provided by
      a low-extinction transmission filter. Pulses with close parameters are obtained
      despite considerable difference in amplifier gain at the pulse train wavelengths
      owing to a strong gain-equalization mechanism provided by the frequency-shifted
      feedback.

PMID- 18091817
TI  - High-power diode-cladding-pumped Tm-doped silica fiber laser.
AB  - The operation of a diode-pumped Tm-doped silica fiber laser that uses the
      cladding-pumping arrangement to produce high-power cw output at wavelengths near
      2 microm is reported. We obtained a maximum output power of 5.4 W at a slope
      efficiency of 31% with respect to the launched pump power at a total optical-to
      optical efficiency of 22%. The fiber-laser output wavelength was tuned between
      1.880 and 2.033 microm by adjustment of the fiber length, with >4W of power
      obtainable from 1.94 to 2.01 microm. Self-pulsations detected in the output from
      the double-clad fiber laser may indicate the presence of ion-clustering effects.

PMID- 18091818
TI  - Broadband semiconductor saturable-absorber mirror for a self-starting mode-locked
      Cr:forsterite laser.
AB  - We report a low-loss broadband semiconductor saturable-absorber mirror (SESAM)
      that uses gold film as the reflector. A semiconductor- SiO(2) double-layer stack
      enhances the reflectivity of the gold film. This low-loss SESAM was used in a
      mode-locked Cr:forsterite laser to produce self-starting 20-fs-scale laser pulses
      at 1.3 microm . The structure can be applied to SESAM's for other wavelengths.

PMID- 18091819
TI  - 100-TW sub-20-fs Ti:sapphire laser system operating at a 10-Hz repetition rate.
AB  - We developed a compact three-stage Ti:sapphire amplifier laser system that
      produced peak power in excess of 100 TW for a pulse duration of less than 19 fs
      and an average power of 19 W at a 10-Hz repetition rate. A final 40-mm-diameter
      Ti:sapphire amplifier is pumped by a Nd:YAG master-oscillator-power-amplifier
      system that produces ~7-J output of 532-nm radiation. The spatial beam quality is
      approximately 2 times diffraction limited for the full amplified compressed
      output pulse. With f/3 optics, this system should therefore be capable of
      producing a focused intensity of ~3x10(20) W/cm(2) .

PMID- 18091820
TI  - Picosecond-resolution study of nonlinear scattering in carbon black suspensions
      in water and ethanol.
AB  - The physical origin of the nonlinear scattering of light induced by focusing of
      intense laser pulses onto carbon black suspensions (CBS's) is discussed through
      the interpretation of limitation, time-resolved pump-probe transmission, and
      angularly and time-resolved scattering experiments performed with picosecond
      resolution. Comparison of the experimental results performed on two different
      solutions of CBS's in water and in ethanol leads us to the conclusion that the
      scattering phenomenon begins most probably with growing microplasmas and that the
      influence of the solvent is significant only at longer times.

PMID- 18091821
TI  - Amplitude and phase characterization of 4.5-fs pulses by frequency-resolved
      optical gating.
AB  - The technique of second-harmonic generation frequency-resolved optical gating is
      applied to measure the intensity and the phase of 4.5-fs pulses resulting from
      the fiber-compressed output of a cavity-dumped Ti:sapphire laser.
      Characterization of even shorter optical pulses by this method should also be
      feasible.

PMID- 18091822
TI  - Information, resolution, and space-bandwidth product.
AB  - The information capacities of two-dimensional optical low-pass channels are
      discussed. Coherent and incoherent systems operating under finite optical power
      and area constraints are characterized in terms of two criteria:spacebandwidth
      product (SBP; the number of pixels required for achieving maximum information
      capacity) and resolution (G(min); the smallest spot size capable of supporting
      positive capacity gain). A coherent system operating with an initial signal-to
      noise ratio (SNR) of 5 can achieve a 48% capacity gain by operating at an optimal
      SBP that is 3.4 times that of the nominal system. The same system has a
      resolution that is 0.31 times nominal. Incoherent systems experience additional
      SNR loss, and with an initial SNR of 5 they achieve capacity gains of 29% at the
      optimal SBP of 2.8 times nominal. The incoherent system resolution is found to be
      0.4 times nominal.

PMID- 18091823
TI  - Measurement of weak transmittances by stochastic resonance.
AB  - We use stochastic resonance to measure weak transmittance amplitudes that are
      below the instrumental detection limit. Gaussian noise is added to the
      subthreshold (chopped) transmittance signal T(t) before detection by a crossing
      detector that uses a dc reference signal B>0. Without noise, no measurement is
      possible because T(t)<B. A fourfold improvement has been obtained in the
      detection limit, permitting the measurement of amplitudes that are as small as
      0.25B.

PMID- 18091824
TI  - Binary computer-generated holograms for security applications from a synthetic
      double-exposure method by electron-beam lithography.
AB  - We have developed a new multiplexing method for producing binary computer
      generated holograms (CGH's) for security applications. This method is based on
      double recording of two types of coding method upon binary CGH's. The CGH
      synthesized by the proposed method can have multiple image planes from the region
      close to the hologram (image region) to infinity (Fraunhofer region) without
      severe degradation of reconstructed images in the image region. A CGH containing
      simultaneous image- and Fourier-type holograms is fabricated by electron-beam
      lithography. Some experimental results are presented.

PMID- 18091825
TI  - Direct fabrication of microgratings in fused quartz by laser-induced plasma
      assisted ablation with a KrF excimer laser.
AB  - We report precision microfabrication of fused quartz by laser ablation with a
      conventional UV laser for what is believed to be the first time. A high-quality
      micrograting structure is fabricated in fused quartz by a novel technique of
      laser-induced plasma-assisted ablation with a single KrF excimer laser (248 nm).
      The plasma generated from a metal target by laser irradiation effectively assists
      in ablation of the fused-quartz substrate by the same laser beam, although the
      laser beam is transparent to the substrate. A grating with a period of 1.06 mum
      is achieved by use of a phase mask. We can control the grating depth to 300 nm by
      changing the pulse number. This technique permits high-quality microfabrication
      of electronic and optoelectronic devices based on fused quartz and related
      silicate materials by use of a conventional UV laser.

PMID- 18091826
TI  - Two-dimensional angular optical scattering for the characterization of airborne
      microparticles.
AB  - Two-dimensional angular optical scattering (TAOS) is recorded for several
      particle shapes and configurations. A lens is used to collect a large solid angle
      of the light and transform the angular profile into a planar distribution
      according to the Abbe sine condition. Qualitative agreement is found between
      experiment and theory for the TAOS from spheroids having the same aspect ratio
      but different sizes. A distinctive irregular island structure is observed in the
      TAOS from clusters of Bacillus subtilis spores and polystyrene latex spheres. The
      density per solid angle of these islands is found to increase with cluster
      diameter.

PMID- 18091827
TI  - Hemispherical-rod microlens as a variant fractional Fourier transformer.
AB  - It is shown that a hemispherical-rod microlens can act as a fractional Fourier
      transform device with a continuously varying degree of fractionality. It is
      believed to be the first proposed device to perform such a task; its most
      immediate applications include optical tomography.

PMID- 18091828
TI  - The diffusion coefficient depends on absorption.
AB  - The diffusion approximation is widely invoked to model the propagation of light
      in turbid media. When absorption is not weak in comparison with scattering, there
      is currently a controversy as to if, and how, the diffusion coefficient depends
      on absorption. Here it is shown that better agreement with random walk simulation
      is obtained if the photon-diffusion coefficient is taken as
      D=c/(3micro(s)(')+micro(a)) . One can reconcile this result with recent work
      advocating D=c/3micro(s)(') by noting that the diffusion equation must be
      correspondingly changed to a telegrapher's equation.

PMID- 18091829
TI  - Orientational gratings in dye-doped polymer-dispersed liquid crystals induced by
      the photorefractive effect.
AB  - We report the observation of orientational gratings induced by the
      photorefractive effect in dye-doped polymer-dispersed liquid crystals. The
      photorefractive origin of the grating-induction effect is supported by the
      results of two-beam coupling experiments and by the possibility of erasing the
      grating by uniform illumination. For all the samples a stable memory effect was
      observed.

PMID- 18091830
TI  - Cascaded second-harmonic and sum-frequency generation of a CO2 laser by use of a
      single quasi-phase-matched GaAs crystal.
AB  - Cascaded second-harmonic and sum-frequency generation were used to obtain the
      third harmonic of a CO(2) laser in a single quasi-phase-matched GaAs crystal.
      Both continuous-wave and pulsed regimes with a single-pass configuration were
      studied. The continuous case confirmed the good capability of the GaAs stack to
      bear high average power density. In the pulsed regime a 0.66% peak power
      conversion efficiency was achieved for the third harmonic when the laser was
      pumping at 8.2 MW/cm(2) , in fair agreement with theoretical predictions.

PMID- 18091831
TI  - Efficient second-harmonic generation of a CO2 laser with a quasi-phase-matched
      GaAs crystal.
AB  - We report on the fabrication and characterization of 5-mm-long quasi-phase
      matched diffusion-bonded GaAs crystals designed for frequency doubling of a CO(2)
      laser. Second-harmonic generation of a pulsed laser yielded up to 24% peak power
      efficiency at 20 MW/cm(2) . Tunability and laser damage threshold are also
      investigated.

PMID- 18091832
TI  - Excitation and bistability of self-trapped signal beams in optical parametric
      oscillators.
AB  - In a doubly resonant degenerate optical parametric oscillator below threshold the
      signal beam can be trapped in the form of stable bright temporal or spatial
      solitons. We characterize these soliton families and discuss how to excite them.

PMID- 18091833
TI  - High-resolution zero-dispersion wavelength mapping in single-mode fiber.
AB  - We present a new noninvasive technique for measuring the spatial variation of the
      zero-dispersion wavelength (lambda(0)) in single-mode fibers. This technique uses
      low-power continuous-wave lasers and is simple to implement. When applying this
      technique to dispersion-shifted fibers, we can resolve subnanometer fluctuations
      in lambda(0) with a potential spatial resolution of better than 100 m. We also
      discuss and show the limits of this and other techniques that arise from
      polarization-mode dispersion in the fibers.

PMID- 18091834
TI  - Long-distance 40-Gbit/s soliton transmission over standard fiber by use of
      dispersion management.
AB  - We demonstrate, through numerical simulations, the possibility of transmitting
      solitonlike pulses over 2000 km of standard fiber at a single-channel data rate
      of 40 Gbits/s. The system used here employs a novel dispersion map to overcome
      the large fiber dispersion. The longest transmission distance was achieved with
      pulses that did not exhibit the enhanced energy normally associated with
      dispersion management and indeed had lower energy than an equivalent average
      soliton.

PMID- 18091835
TI  - Fiber grating synthesis by use of time-frequency representations.
AB  - We propose a method to reconstruct the grating period in fiber grating structures
      from the field reflection coefficient or the related impulse response. The method
      is based on the joint time-frequency signal analysis and uses the Wigner-Ville
      and the spectrogram distributions. Results show good agreement between exact and
      reconstructed functions.

PMID- 18091836
TI  - Simple approach to coupling in textured planar waveguides.
AB  - We develop a self-consistent Green's function technique to calculate the full
      photonic band structure for guided modes in slab waveguides that have been
      textured in one dimension with a thin surface grating. The technique is
      conceptually simple and can easily be reduced to an eigenvalue problem by use of
      approximations similar to those used in conventional coupled-mode theories. We
      show that this approach yields the correct TM-TM coupling coefficient at oblique
      incidence and provides a transparent interpretation for its vanishing at a
      critical angle.

PMID- 18091837
TI  - Mechano-optical waveguide on-off intensity modulator.
AB  - High-extinction on-off modulators are essential for channel selection in
      integrated-optical sensor arrays. We report a standard SiON-technology-based
      electrostatically driven integrated mechano-optical waveguide on-off intensity
      modulator. On-off modulation is achieved by movement of an absorbing element into
      and out of the evanescent field of the guided mode. An extinction ratio of >37 dB
      at an actuation voltage of <30 V was achieved in a 6 mm x 4 mm device for a
      wavelength of 632.8 nm. Full wafer-scale fabrication is made possible by use of
      chemical mechanical polishing and aligned wafer bonding.

PMID- 18091838
TI  - Resonant sideband generation in stretched-pulse fiber lasers.
AB  - Resonant sideband production in stretched-pulse fiber lasers operating with net
      normal dispersion is investigated. A theoretical formulation is compared with
      numerical modeling and experimental results. The inherent difference from
      sideband generation in soliton lasers is discussed. We also consider the
      implications of sideband formation in related dispersion-managed soliton
      transmission systems.

PMID- 18091839
TI  - Repetition-rate scaling of a kinetically enhanced copper-vapor laser.
AB  - The output power of a kinetically enhanced Cu-vapor laser is shown to increase
      linearly with pulse repetition frequency to an experimental limit of 22 kHz.
      Output power of >150 W has been produced by a medium-scale (38-mm diameter, 1.55
      m long) device operating at 22 kHz.

PMID- 18091840
TI  - Beam steering with two ferroelectric liquid-crystal spatial light modulators.
AB  - Ferroelectric liquid-crystal spatial light modulators (FLC SLM's) are binary
      modulating devices that can be used for flexible beam steering in the microsecond
      range. Because they are binary, at least 60% of the light power is lost to
      unwanted diffraction orders, however. We suggest the use of a second FLC SLM,
      synchronously operating in amplitude-modulating mode, to block the unwanted
      orders. The proposed beam-steering method is demonstrated in a simple scanner
      experiment. The efficiency of the suggested beam steerer is independent of the
      number of steering directions.

PMID- 18091841
TI  - Beam-quality measurement of a focused high-order harmonic beam.
AB  - Using a multilayer spherical mirror, we focus the high-order harmonic radiation
      produced near 55 nm by the nonlinear interaction of an intense femtosecond laser
      pulse and a xenon gas jet. The focused XUV beam is characterized by a knife-edge
      technique in the focal region and by far-field imaging. We show that good-quality
      beams, nearly two times diffraction limited, can be generated, a conclusion that
      is at variance with recent predictions of harmonic phase-front distortion. Spot
      sizes close to 10 microm are obtained, resulting in a high XUV intensity.
      Increasing the gas density and the length of the generating medium results in a
      large increase in the divergence in and degradation of the beam quality.

PMID- 18091842
TI  - 5-GHz repetition-rate dual-wavelength pulse-train generation from an intracavity
      frequency-modulated Er-Yb:glass laser.
AB  - We report the experimental demonstration of nearly transform-limited dual
      wavelength pulse trains at a 5-GHz repetition rate that were generated by
      spectral filtering of an intracavity 2.5-GHz frequency-modulated Er-Yb bulk-glass
      laser operating at the 1533-nm wavelength. Highly stable dual-wavelength pulse
      trains with approximately 165-GHz frequency separation, approximately 48-ps pulse
      duration, and approximately 1-mW average single-mode fiber-coupled power were
      obtained.

PMID- 18091843
TI  - Multichannel liquid-crystal-based wave-front corrector with modal influence
      functions.
AB  - We report on a multichannel liquid-crystal-based wave-front corrector with smooth
      modal influence functions. The phase is controlled by application of spatially
      localized ac voltages to a distributed voltage divider formed by a liquid-crystal
      layer sandwiched between a high-conductance and a low-conductance electrode. The
      shape of the influence function depends on the control frequency and material
      parameters of the distributed voltage divider. We have experimentally realized a
      reflective modulator controlled by an array of 16 x 16 electrodes, providing
      phase control with an amplitude of approximately 16 pi at lambda =633 nm with a
      time constant of the order of tens of milliseconds. We experimentally
      demonstrated that the amplitude of each influence function can be controlled by
      change of the control voltage, whereas the width of the influence function is
      controlled by the frequency of the control voltage in a range of approximately 1
      mm to the full width of the modulator aperture.

PMID- 18091844
TI  - Anisotropic antireflection coatings: design and fabrication.
AB  - We discuss the design and fabrication of coatings that are antireflecting for p 
      polarized light at normal incidence and are purposely reflecting for s -polarized
      light. A single birefringent material, such as obliquely deposited zirconium
      oxide, forms the layers of the coating. Typical experimental results for a six
      layer zirconium oxide anisotropic antireflection coating are R(p) = 0.2% and R(s)
      = 4.9%. Potential applications of the coatings include polarization-selection
      devices for lasers.

PMID- 18091845
TI  - High-efficiency guided-mode resonance filter.
AB  - A high-efficiency guided-mode resonance reflection filter is reported. The device
      consists of a surface-relief photoresist grating and an underlying HfO (2)
      waveguide layer deposited on a fused-silica substrate. The spectral response
      measured with a dye-laser beam at normal incidence exhibited a peak reflectance
      of 98% at a wavelength of 860 nm with sideband reflectance below approximately 5%
      extending over the wavelength range provided by the dye (800-900 nm). At normal
      incidence the filter linewidth was 2.2 nm. High-efficiency double-peak resonances
      occurred at nonnormal incidence, with the spectral locations of the maxima
      vayring with the incidence angle. The filter response at various angles of
      incidence agreed well with the theoretically calculated reflectance curves.

PMID- 18091846
TI  - 4Pi confocal microscopy with alternate interference.
AB  - We introduce 4Pi confocal microscopy with destructive interference of converging
      waves. Linear lobe deconvolution as well as nonlinear restoration of 4Pi confocal
      raw data with their point-spread functions (PSF's) leads to almost-identical
      images, irrespective of whether the 4Pi confocal PSF relies on constructive or
      destructive interference. Three-dimensional imaging of microtubules of a mouse
      fibroblast cell yielded an axial resolution near 100-nm in both cases. Moreover,
      restoration of 4Pi confocal images of the same object with alternate phases is
      introduced as a powerful test for (nonlinear) image restoration.

PMID- 18091847
TI  - Second-order filtering and sensing with partially coupled traveling waves in a
      single resonator.
AB  - The counterpropagating waves in a single traveling-wave cavity can be partially
      coupled by means of a small perturbation such as a notch. When it is side coupled
      to a waveguide, this single cavity yields a general second-order (Chebyshev)
      reflection response in the waveguide, which is useful for narrow-bandwidth
      reflecting applications. In a different application, the cavity amplifies small
      reflections induced by external perturbations, thus finding use in ultrafine
      sensing. Amplification factors as great as 10(12) are predicted for the highest-Q
      microsphere resonators. The analytic theory of these devices is presented.

PMID- 18091848
TI  - Omnidirectional reflection from a one-dimensional photonic crystal.
AB  - We demonstrate that one-dimensional photonic crystal structures (such as
      multilayer films) can exhibit complete reflection of radiation in a given
      frequency range for all incident angles and polarizations. We derive a general
      criterion for this behavior that does not require materials with very large
      indices. We perform numerical studies that illustrate this effect.

PMID- 18091849
TI  - Closed-loop phase-shifting interferometry with a laser diode.
AB  - A closed-loop phase-shifting Fizeau-type interferometer at lambda=633 nm was
      constructed with the direct frequency modulation of laser diodes. The
      interferometer is servo controlled fully in the phase domain where optical phases
      are detected by a two-frequency optical heterodyne method. Stepwise phase
      shifting was accomplished with good stabilization against external disturbances
      (vibration, air flow, etc.) and laser frequency fluctuations.

PMID- 18091850
TI  - Circular solitons do not exist in photorefractive media.
AB  - The shape of two-dimensional solitary beams propagating in photorefractive media
      with an externally applied field is studied. The analytical results indicate
      that, for both focusing and defocusing nonlinearities, radially symmetric self
      channeled beams do not exist. Some recent experiments are interpreted in light of
      the present results.

PMID- 18091851
TI  - Complete pulse characterization at 1.5 mum by cross-phase modulation in optical
      fibers.
AB  - Cross-phase modulation in optical fibers has been used for complete
      characterization of ultrashort pulses by a modified frequency-resolved optical
      gating (FROG) measurement technique. This technique has been used for
      characterization of picosecond pulses at 1.5mum with energy as low as 24 pJ, and
      the results are in excellent agreement with second-harmonic generation (SHG)-FROG
      characterization. The use of an optical waveguide gives measurement sensitivity
      comparable with that of SHG-FROG but without any temporal ambiguity in the
      retrieved pulse.

PMID- 18091852
TI  - Influence of cascading phenomena on a type I second-harmonic wave generated by an
      intense femtosecond pulse: application to the measurement of the effective second
      order coefficient.
AB  - We have studied the influence of cascaded second-order effects on the spectral
      density of a second-harmonic pulse generated in thin KDP and beta-barium borate
      crystals by an intense femtosecond pulse. A noticeable evolution of spectral
      density is recorded for any value of phase mismatch. This evolution is in good
      agreement with the solution of the nonlinear propagation equation and allows a
      simple direct measurement of the effective susceptibility of the studied
      crystals.

PMID- 18091853
TI  - Wavelength-tunable high-power picosecond pulses from a fiber-pumped diode-seeded
      high-gain parametric amplifier.
AB  - We describe a high-gain optical parametric amplifier (OPA) and optical parametric
      generator (OPG) system pumped by a fiber chirped-pulse amplification source based
      on novel large-mode-area fiber components. 45-nJ OPG thresholds and 34% pump
      signal conversion efficiencies are obtained for ~4-ps pulses. OPA gains in excess
      of 75 dB and pump-signal conversion efficiencies of ~39% (external) are
      demonstrated. Furthermore, we show that injection seeding of such high-gain
      parametric devices by use of a low-power continuous-wave beam results in high
      power (>18-kW) picosecond pulses with a time-bandwidth produce of ~0.65, some ten
      times less than from a free-running OPG. Using such an approach, we obtain 2.7-ps
      50-nJ pulses at 1.310 mum .

PMID- 18091854
TI  - Increased spectral bandwidths in nonlinear conversion processes by use of
      multicrystal designs.
AB  - The fourth-harmonic generation of broadband 243-nm radiation is reported. The
      broadband radiation is achieved by implementation of a multicrystal design to
      overcome spectral bandwidth limitations, and a plane-wave analysis is developed
      that shows increased spectral bandwidths for these designs. The fourth harmonic
      of a Cr:LiSAF laser operating at 972 nm is generated in beta-barium borate (BBO).
      The results demonstrate a spectral bandwidth at 243 nm more than five times
      broader than that which is expected from a single BBO crystal of equivalent
      length.

PMID- 18091855
TI  - Vibrationally resolved sum-frequency generation with broad-bandwidth infrared
      pulses.
AB  - We present a novel procedure for vibrationally resolved sum-frequency generation
      (SFG) in which a broad-bandwidth IR pulse is mixed with a narrow-bandwidth
      visible pulse. The resultant SFG spectrum is dispersed with a spectrograph and
      detected in parallel with a scientific-grade CCD detector, permitting rapid and
      high signal-to-noise ratio data acquisition over a 400-cm(-1) spectral region
      without scanning the IR frequency. Application to the study of a self-assembled
      monolayer of octadecanethiol is discussed.

PMID- 18091856
TI  - Image restoration through aberrant media by optical phase conjugation in a type
      II three-wave mixing interaction.
AB  - Restoration of an image through an aberrant plate has been achieved by use of
      optical phase conjugation in a type II parametric interaction in which the
      amplified signal and idler waves are reflected back through the aberrant medium.
      The resolution of the restored phase-conjugate images is equal to 0.18 mm, and
      the amplification gain is ~4dB.

PMID- 18091857
TI  - Interchannel pulse collision in a wavelength-division-multiplexed system with
      strong dispersion management.
AB  - We develop a perturbation theory to analytically calculate the effects of
      complete and incomplete interchannel collisions of Gaussian pulses in a
      wavelength-division-multiplexed system with strong dispersion management. We show
      that, for complete collisions, the collision-induced frequency shift of a
      Gaussian pulse is negligible, whereas its position shift is significant and can
      be found in a simple analytical form. For strong dispersion management we find
      that incomplete collisions can be neglected, whereas for dispersion management of
      moderate strength the contribution of the incomplete collisions can be
      significant. The analytical predictions are in satisfactory agreement with
      numerical results. We also give an estimate of the limit imposed on the
      transmission distance by such collisions.

PMID- 18091858
TI  - Enhanced range for OTDR-like dispersion map measurements.
AB  - We report on enhancement of the range, reliability, and accuracy of optical-time
      domain-reflection- (OTDR-) like measurement of an optical fiber's dispersion map,
      D(z), through the combined use of Raman gain, an appropriate seed at the four
      wave mixing frequency, and a greatly improved algorithm for reduction of the
      data. In particular, in measurements made from only one end of the fiber, we have
      demonstrated a range of 75 km in dispersion-shifted fiber and of 22.5 km in high
      loss dispersion-compensating fiber.

PMID- 18091859
TI  - Experimental control of a chaotic semiconductor laser.
AB  - We have experimentally controlled the chaotic output of a single-mode
      semiconductor laser pumped near threshold and subject to optical feedback. We
      used a novel technique called dynamic targeting, which was theoretically proposed
      by Wieland et al. [Opt. Lett. 22, 469 (1997)]. Optical feedback causes the
      semiconductor laser to undergo a bifurcation cascade that exhibits regions of
      stability, periodicity, chaos, and coherence collapse. By adjusting the feedback
      phase simultaneously as the feedback strength was varied we steered the laser
      into the stable maximum gain mode, and thus we stabilized the system at maximum
      intensity.

PMID- 18091860
TI  - Intense xenon capillary discharge extreme-ultraviolet source in the 10-16-nm
      wavelength region.
AB  - We have observed intense extreme-ultraviolet emission, within the 10-16-nm
      wavelength range, emitted by a xenon capillary discharge plasma. Within a 0.3-nm
      bandwidth centered at 13.5 nm the axial emission intensity was comparable with
      that from the brightest laser-produced plasma sources, and a similar intensity
      was measured at approximately 11.3 nm. This source could thus be suitable for
      extreme-ultraviolet imaging applications, such as extreme-ultraviolet
      lithography.

PMID- 18091861
TI  - Programmable dispersion compensation and pulse shaping in a 26-fs chirped-pulse
      amplifier.
AB  - We have constructed a 26-fs chirped-pulse amplifier that incorporates a
      programmable liquid-crystal spatial light modulator in the pulse stretcher. The
      modulator serves a dual purpose. First, we apply frequency-dependent phase shifts
      to compensate for cubic, quartic, and nonlinear phase dispersion in the
      amplifier, which results in a reduction in pulse duration from 32 to 26 fs, in
      agreement with the transform limit of the amplified pulse spectrum. Second, we
      are able to produce high-fidelity compressed amplified shaped pulses by applying
      phase masks directly within the stretcher. Shaped pulse energies of greater than
      1 mJ are routinely obtained.

PMID- 18091862
TI  - Dispersion filter for spectral and spatial resolution of pure rotational Raman
      scattering.
AB  - A new filtering technique for Raman spectroscopy utilizes atomic vapor to
      suppress strong elastic and Rayleigh scattering while simultaneously resolving
      individual rotational Raman lines. Filtered images capture high-resolution
      spectral information in one dimension and spatial resolution in the other
      dimension. The filter is based on resonance enhanced dispersion, where the index
      of refraction varies dramatically. In a simple prism geometry the vapor disperses
      incident radiation according to frequency. A mercury-vapor-based dispersion
      filter has been fabricated, modeled, and demonstrated to capture pure rotational
      Raman scattering from CO(2).

PMID- 18091863
TI  - Light-induced absorption of cerium-doped lead barium niobate crystals.
AB  - Tetragonal lead barium niobate (Pb(1-x)Ba(x)Nb(2)O(6);1-x<0.63) crystals are
      promising photorefractive materials for applications such as holographic data
      storage. Measurements of light-induced absorption in Ce-doped lead barium niobate
      (Pb(0.5)Ba(0.5) Nb(2)O(6)) were performed. The induced absorption that was due to
      the presence of shallow traps was as large as 0.3cm(-1) at 633 nm and exhibited
      saturation behavior at green-pump intensity greater than 2W/cm(2) . The temporal
      profile of the dark decay was a double exponential, and the activation energies
      of the slow- and the fast-decaying components were determined to be 0.16 and 0.3
      eV, respectively.

PMID- 18091864
TI  - Grazing holographic projection of object-adapted fringes for shape measurements
      with enhanced sensitivity.
AB  - A new method of fringe projection for shape measurement is presented. We use a
      combination of object-adapted fringes and holographic grazing projection to
      determine shape deviations of a turbine blade. If the shape of a test object is
      correct, a fringe grid with constant period is detected by the camera. The object
      adapted fringes are projected coherently onto the master object, and a hologram
      is taken. If the hologram is reconstructed, grazing incidence of object-adapted
      fringes can be realized. Grazing holographic projection allows for higher
      triangulation angles and therefore increased sensitivity. Even small shape
      deviations can be detected and quantitatively evaluated with fast algorithms. The
      method can be extended to multiple exposed holograms to examine deep objects.

PMID- 18091865
TI  - Bending sensitivity of in-series long-period fiber gratings.
AB  - The interference fringes formed in a long-period fiber grating pair are sensitive
      to the loss in the cladding mode, which can be induced by bending or by coating
      on the fiber. Assuming that there is no loss and that both gratings are
      identical, the interference fringes are shown to have 100% contrast when each
      grating has 50% transmissivity. By contrast, if the cladding mode is absorbed or
      scattered the fringe contrast is shown to be degraded. The spectral behaviors of
      a long-period fiber grating pair with loss is analyzed by the coupled-mode theory
      and is compared with experimental results.

PMID- 18091866
TI  - Wave-plate polarizing beam splitter based on a form-birefringent multilayer
      grating.
AB  - We have fabricated a novel device that acts as a quarter-wave plate at normal
      incidence and as a polarizing beam splitter at an angle of incidence of ~40 deg .
      The device is made from a multilayer (SiO(2) /Si(3)N(4)) surface-relief zeroth
      order one-dimensional grating with a period of 0.3 mum . The device is designed
      for an operating wavelength of 632.8 nm. We designed the device by using rigorous
      coupled-wave analysis and fabricated it by direct-write electron-beam lithography
      and reactive ion etching. Measurements confirmed the performance of the device as
      a wave plate and as a polarizing beam splitter.

PMID- 18091868
TI  - Design of diffractive axicons for partially coherent light.
AB  - We propose a novel method of designing diffractive axicons for use in spatially
      partially coherent illumination. The design procedure is based on the results
      obtained by the stationary-phase method. The technique leads to a coherence
      dependent differential equation with appropriate boundary conditions for the
      axicon phase function. We demonstrate the method with annular-aperture axicons
      generating extended focal line segments of uniform on-axis intensity.

PMID- 18091867
TI  - Measurement and calculation of the two-dimensional backscattering Mueller matrix
      of a turbid medium: errata.
AB  - In our recent Letter,(1) several typographical errors were present. On p. 487, in
      Fig. 2, the equations for the following Mueller matrix elements should read as
      S(14) = (RO - LO), S(22) = (HH + VV) - (HV + VH), S(23) = (PH + MV) - (PV + MH),
      S(24) = (RH + LV) - (RV + LH), S(32) = (HP + VM) - (HM + VP), S(33) = (PP + MM) -
      (PM + MP), S(34) = (RP + LM) - (RM + LP), S(41) = (OR + OL), S(42) = (HR + VL) -
      (HL + VR), S(43) = (PR + ML) - (PL + MR), and S(44) = (RR + LL) - (RL + LR). Also
      on p. 487, in the left-hand column, line 10 from the top should read as follows:
      mfp? = 1/[mua + mus(1 - g)], was 0.957 cm.

PMID- 18091869
TI  - Signatures of electromagnetic surface-shape resonances in scattering of pulsed
      beams from surface defects.
AB  - We predict theoretically that electromagnetic resonances supported by surface
      defects can be detected experimentally by study of the scattering of
      electromagnetic pulses from these defects, and we formulate the optimal
      conditions for such experiments. Numerical scattering simulations confirm that
      the proposed scattering probes unambiguously identify resonance signatures. The
      approach that we suggest proves to be superior to conventional analysis of
      features in the dependence of the far-field intensity of scattered monochromatic
      light on its frequency, since these features do not necessarily point at resonant
      frequencies.

PMID- 18091870
TI  - Spatial channels for communicating with waves between volumes.
AB  - I show that there is an exact, complete method for finding the orthogonal spatial
      channels, or communications modes, between two arbitrary volumes, and the
      associated connection strengths, for the case of scalar waves. I also show that
      the sum of the squared connection strengths is given exactly by a simple volume
      integral. The method is illustrated by a calculation for a particular extreme
      pair of volumes, and the communications modes are interpreted physically as the
      modes of a double phase-conjugate resonator.

PMID- 18091871
TI  - Engineered omnidirectional external-reflectivity spectra from one-dimensional
      layered interference filters.
AB  - Owing to optical refraction, external rays that are incident upon a high
      refractive-index medium fall within a small internal cone angle. A one
      dimensionally periodic Bragg structure can reflect over an angular acceptance
      range that is greater than the small internal refraction cone, if the internal
      refractive-index contrast is sufficient. Thus Winn et al. [Opt. Lett. (to be
      published)] charted the range of refractive indices at which omnidirectional
      external reflection occurs. A wide spectral gap requires a high-index contrast.
      It is proposed that, by chirping or grading the periodicity of the structure, one
      can cover an arbitrarily wide spectral range with only a modest index contrast
      and, furthermore, that arbitrary spectral shapes can be produced. The graded
      periodicity approach requires only a modest index contrast, provided that the
      average refractive index is >2 .

PMID- 18091872
TI  - Transverse modulational instability of counterpropagating quasi-phase-matched
      beams in a quadratically nonlinear medium.
AB  - We find the threshold and the generation angle for transverse instability of
      quasi-phase-matched counter-propagating fundamental and second-harmonic beams in
      a bulk c((2)) medium. Numerical estimates indicate that the instability should be
      observable with currently available materials.

PMID- 18091873
TI  - Ultrafast addressing by use of spatial solitons in traveling-wave parametric
      amplification.
AB  - We demonstrate that single, narrow solitary beams can be locally excited in a
      large-beam pump field and that their position is adjustable within a 50-cell
      matrix by use of a 15-pJ seeding signal as an addressing control parameter.

PMID- 18091874
TI  - Photorefractive line waves.
AB  - We study self-channeling of light waves in a rotated cut of crystals of the 4mm
      and the 6mm classes, whose dominant mechanism is photorefractive diffusion
      nonlinearity. The existence of photorefractive line waves that can be guided
      along the edge of the crystal is suggested and analyzed.

PMID- 18091875
TI  - Fiber spin-profile designs for producing fibers with low polarization mode
      dispersion.
AB  - Using coupled-mode theory, we develop a theoretical model to analyze the effects
      of fiber spin profiles on polarization mode dispersion (PMD). Constant,
      sinusoidal, and frequency-modulated spin profiles are examined, and phase
      matching conditions are analyzed. Our analysis shows that PMD can be reduced
      effectively by use of frequency-modulated spin profiles.

PMID- 18091876
TI  - Group-velocity dispersion in photonic crystal fibers.
AB  - The dispersion properties of photonic crystal fibers are calculated by expression
      of the modal field as a sum of localized orthogonal functions. Even simple
      designs of these fibers can yield zero dispersion at wavelengths shorter than
      1.27 mum when the fibers are single mode, or a large normal dispersion that is
      suitable for dispersion compensation at 1.55 mum.

PMID- 18091877
TI  - Fabrication of high-rejection low-loss single-passband filters in cladding
      depressed fiber by the chirped-grating concatenation method.
AB  - High-rejection-low-loss single-passband filters have been successfully fabricated
      by the chirped-grating concatenation method in a cladding depressed fiber. The
      enhanced photosensitivity, the enlarged bandgap between the Bragg resonance and
      the cladding modes, and the effective suppression of the cladding-mode
      outcoupling of the cladding depressed fiber permitted what is to our knowledge
      the first achievement of an ~1-dB loss in the passband and 50-dB rejection for a
      50-nm-wide stop band covering the entire amplified spontaneous emission spectral
      range of an Er-doped fiber amplifier.

PMID- 18091878
TI  - Multiscale pulse dynamics in communication systems with strong dispersion
      management.
AB  - The evolution of an optical pulse in a strongly dispersion-managed fiber-optic
      communication system is studied. The pulse is decomposed into a fast phase and a
      slowly evolving amplitude. The fast phase is calculated exactly, and a nonlocal
      equation for the evolution of the amplitude is derived. In the limit of weak
      dispersion management the equation reduces to the nonlinear Schrodinger equation.
      A class of stationary solutions of this equation is obtained; they represent
      pulses with a Gaussian-like core and exponentially decaying oscillatory tails,
      and they agree with direct numerical solutions of the full system.

PMID- 18091879
TI  - Generation of multiorder Stokes and anti-Stokes lines in a Brillouin erbium-fiber
      laser with a Sagnac loop mirror.
AB  - We have demonstrated a novel multiwavelength lasing scheme in which a Brillouin
      erbium-fiber laser with a Sagnac loop mirror and a metal-coated planar mirror
      were used. The Sagnac loop permitted the simultaneous presence of a stimulated
      Brillouin scattering (SBS) pump and Stokes lines within the loop and thus
      generated high-order Stokes and anti-Stokes waves through a four-wave mixing
      (FWM) process. A total of 34 lines of Stokes and anti-Stokes waves with 0.08-nm
      line spacing was generated through the SBS and FWM processes with 1.5-mW SBS pump
      power at 1561 nm and 80-mW erbium-doped-fiber pump power.

PMID- 18091880
TI  - Dispersion-managed solitons in the normal dispersion regime: a physical
      interpretation.
AB  - We present an analytic description of dispersion-managed soliton propagation
      based on split-step and variational models. Using these models, we derive the
      threshold map strength for the existence of dispersion-managed solitons in the
      normal dispersion regime and obtain a bound on the maximum normal average
      dispersion.

PMID- 18091881
TI  - Reduced model of the evolution of the polarization states in wavelength-division
      multiplexed channels.
AB  - We have developed a reduced model of the evolution of the polarization states of
      the channels in a wavelength-division-multiplexed system that follows only the
      Stokes parameters for each channel. We apply this model to demonstrating that the
      expected repolarization of polarization-scrambled signals is small. We verify our
      results by comparing them with numerical simulations with realistic parameters.

PMID- 18091882
TI  - Formation of planar optical waveguides in the new nonlinear gadolinium calcium
      oxoborate, Ca(4)GdO(BO(3))(3), crystal by 2-MeV He(+) implantation.
AB  - A planar waveguide composed of the new nonlinear material, Ca(4)GdO(BO(3))(3)
      (GdCOB), is reported. This crystal belongs to the calcium oxoborate family. It
      has attractive nonlinear properties that can be of great interest in integrated
      optics applications. We used a method of He(+) implantation to fabricate
      waveguides in GdCOB crystals by creating a buried layer of lowered refractive
      index a few micrometers beneath the surface. Both TE and TM modes were observed.
      Therefore, according to the Y cut of the crystal, refractive-index values of n(x)
      , n(y) , and n(z) were obtained. Index profiles were reconstructed by an improved
      inverse WKB method. The profiles showed a steplike index behavior, indicating
      that the guiding region obtained was of good optical quality.

PMID- 18091883
TI  - High-energy single-transverse-mode Q-switched fiber laser based on a multimode
      large-mode-area erbium-doped fiber.
AB  - We demonstrate that appropriately designed doped multimode fibers provide robust
      single-mode output when used within a fiber laser cavity. Using a novel large
      mode-area fiber, we demonstrate what we believe to be record single-mode (M(2)
      <1.2) pulse energies of >0.5 mJ from a Q -switched fiber laser and even higher
      pulse energies (as high as 0.85 mJ) with slightly compromised spatial-mode
      quality (M(2)<2.0) . This approach offers significant scope for extending the
      range of single-mode output powers and energies that are achievable from fiber
      laser-amplifier systems.

PMID- 18091884
TI  - Correlation between amplitude and phase noise in a mode-locked Cr:LiSAF laser.
AB  - The coherence function between the amplitude and phase fluctuations of a mode
      locked Cr:LiSAF laser has been measured with a time-domain demodulation
      technique. A relatively large correlation has been found for the noise components
      that originate in the pump-power fluctuation. Through an examination of the
      modulation-induced change in the noise power spectral densities, the influences
      of pump-power and cavity-length variations on these fluctuations have been
      investigated.

PMID- 18091885
TI  - Observation of optical bistability in a GaAlAs semiconductor laser under
      intermodal injection locking.
AB  - Experimental observation of optical bistability in a semiconductor laser under
      intermodal injection locking is reported for what is believed to be the first
      time. It is seen that a change in injection power of several microwatts or master
      laser frequency detuning of a few hundred megahertz can induce a change of as
      much as several hundred gigahertz in the lasing frequency of the slave laser. The
      results are in qualitative agreement with theoretical predictions.

PMID- 18091886
TI  - Kilohertz Cr:forsterite regenerative amplifier.
AB  - We report on a tunable regenerative amplifier that is operational in the near
      infrared spectral region from 1230 to 1280 nm based on the vibronic laser
      material Cr:forsterite. Utilizing the technique of chirped-pulse amplification,
      we generated pulses as short as 150 fs at 1255 nm at a repetition rate of 1 kHz.
      Pulse amplification of more than 5 x 10(5) times was observed, with recorded
      output pulse energies of 34 muJ . Implementation of a second-harmonic generator
      yielded 110-fs-duration pulses of 7-muJ energy at 625 nm.

PMID- 18091887
TI  - Chirped-pulse-amplification circuits for fiber amplifiers, based on chirped
      period quasi-phase-matching gratings.
AB  - A new type of compact chirped-pulse-amplification circuit for high-power
      amplification of femtosecond pulses in an optical fiber is demonstrated. This
      circuit is based on a novel pulse compressor, chirped-period quasi-phase-matching
      gratings in electric-field-poled lithium niobate. The main advantages of this
      circuit are simplicity, the small number of components, compactness, and
      wavelength conversion of Er-doped fiber output to the technologically important
      780-nm wavelength region.

PMID- 18091889
TI  - Optical Bloch oscillations in waveguide arrays.
AB  - We show that optical Bloch oscillations can emerge in waveguide arrays with
      linearly varying propagation constants. The existence of localized modes (Wannier
      Stark states) with equidistant wave-number spacing (Wannier-Stark ladder) that do
      not undergo diffraction is analytically proved. The evolution of arbitrary
      initial excitations is described, and potential applications are suggested.

PMID- 18091888
TI  - Observed factorization of excess quantum noise that is due to both polarization
      and spatial mode nonorthogonality.
AB  - When the eigenmodes of a laser cavity are nonorthogonal, the quantum-limited
      linewidth of the laser is larger by an excess-noise factor than the standard
      Schawlow-Townes expression. Mode nonorthogonality can exist in the spatial
      domain, as in unstable-cavity resonators, but also in the polarization domain
      when the two polarization eigenmodes are nonorthogonal. We show experimentally
      that these two contributions are independent of each other, i.e., that the excess
      noise factor factorizes as a product of the spatial and polarization excess-noise
      factors.

PMID- 18091890
TI  - Spatial and temporal filtering of a 10-W Nd:YAG laser with a Fabry--Perot ring
      cavity premode cleaner.
AB  - We report on the use of a fixed-spacer Fabry-Perot ring cavity to filter
      spatially and temporally a 10-W laser-diode-pumped Nd:YAG master-oscillator power
      amplifier. The spatial filtering leads to a 7.6-W TEM (00) beam with 0.1% higher
      order transverse mode content. The temporal filtering reduces the relative power
      fluctuations at 10 MHz to 2.8x10(-9)/ radicalHz, which is 1 dB above the shot
      noise limit for 50 mA of detected photocurrent.

PMID- 18091891
TI  - Low-threshold lasing at the edge of a photonic stop band in cholesteric liquid
      crystals.
AB  - Low-threshold lasing is observed at the edge of the stop band of a one
      dimensional structure-a dye-doped cholesteric liquid-crystal film. The mode
      closest to the edge has the lowest lasing threshold. The rates of spontaneous and
      stimulated emission are suppressed within the stop band and enhanced at the band
      edge. The ratio of right to left circularly polarized spontaneous emission is in
      good agreement with calculated density of photon states.

PMID- 18091892
TI  - Holographic storage of multiple high-capacity digital data pages in thick
      photopolymer systems.
AB  - Multiple digital data pages (480 kbits per page) were holographically recorded
      and retrieved with low bit-error rates in thick (~250- and ~500-mum) photopolymer
      media. The photopolymer systems were fabricated with the optical quality and low
      level of scatter required for digital data storage. We believe that these results
      represent the first demonstration of holographic storage of high-capacity digital
      data pages in photopolymer media with the thickness that will be required for
      such storage densities.

PMID- 18091893
TI  - Contributions of the cornea and the lens to the aberrations of the human eye.
AB  - The relative contributions of optical aberrations of the cornea and the
      crystalline lens to the final image quality of the human eye were studied. The
      aberrations of the entire eye were obtained from pairs of double-pass retinal
      images, and the aberrations of the cornea were obtained from videokeratographic
      data. Third-order spherical aberration and coma were significantly larger for the
      cornea than for the complete eye, indicating a significant role of the lens in
      compensating for corneal aberrations. In a second experiment retinal images were
      recorded in an eye before and after we neutralized the aberrations of the cornea
      by having the subjects wear swimming goggles filled with saline water, providing
      a direct estimate of the optical performance of the crystalline lens.

PMID- 18091894
TI  - High-resolution near-infrared tomographic imaging simulations of the rat cranium
      by use of a priori magnetic resonance imaging structural information.
AB  - Near-infrared (NIR) optical image reconstruction that incorporates magnetic
      resonance image (MRI) structural data was tested in a series of simulated
      reconstructions. NIR diffuse tomography generally suffers from comparatively low
      spatial resolution. By using the fine structural detail that is available with
      MRI, combined with the functional information of NIR spectroscopy, it is possible
      to design a new image-reconstruction methodology that provides high-resolution
      images that are correlated with hemoglobin concentration and oxygen saturation.
      To test this concept a MRI spin-echo image of a rat cranium was used to obtain an
      outline of the bone, brain, and muscle tissues, and this information was
      incorporated into an iterative-based diffuse tomography reconstruction. These
      simulations represent what is believed to be the first attempt at evaluating a
      spatially constrained iterative-reconstruction MRI-NIR imaging modality for brain
      tissue.

PMID- 18091895
TI  - Nonperturbative results for the spectrum of surface-disordered waveguides.
AB  - We calculated the spectrum of normal scalar waves in a planar waveguide with
      absolutely soft randomly rough boundaries. Our approach is beyond perturbation
      theories in the roughness heights and slopes and is based instead on the exact
      boundary scattering potential. The spectrum is proved to be a nearly real
      nonanalytic function of the dispersion zeta(2) of the roughness heights (with
      square-root singularity) as zeta(2)?0 . The opposite case of large boundary
      defects is summarized.

PMID- 18091896
TI  - Photorefraction in lead tin-fluorophosphate glasses.
AB  - Permanent grating patterns have been written directly in lead-tin-fluorophosphate
      glasses by use of UV radiation. The effect of photorefraction is studied in
      different tin-fluorophosphate compositions. Recorded gratings are found to be
      volume rather than surface elements. The induced index changes are comparable
      with those seen in GeO(2)- SiO(2) glasses.

PMID- 18091897
TI  - Observation of two distinct phase states in a self-phase-locked type II phase
      matched optical parametric oscillator.
AB  - We demonstrate self-phase locking in a type II phase-matched optical parametric
      oscillator by mutual injection locking. An intracavity quarter-wave plate
      provides polarization mixing between the orthogonally polarized signal and idler
      that induces signal-idler self-phase locking when their frequency difference is
      within the capture range. We observed two distinct phase states that differ in
      their oscillator thresholds and their signal-idler phase differences, in good
      agreement with theory.

PMID- 18091898
TI  - Experimental observation of photon echoes and power-efficiency analysis in a
      cavity environment.
AB  - We present what is, to our best knowledge, the first experimental demonstration
      of echo signals generated from a sample in an optical cavity. The configuration
      allows us to use an optically thin sample and still have high effective
      absorption as well as relatively uniform excitation in the longitudinal direction
      within the sample. We observed echo signal power of up to twice that of certain
      input fields. The observed efficiency is much greater than the normally expected
      few percent. By using an input field encoded with a bit sequence, we also show
      that the cavity does not introduce significant distortion into the reproduced
      signal.

PMID- 18091899
TI  - Continuous-wave optical parametric oscillator based on periodically poled
      KTiOPO(4).
AB  - We report what is to our knowledge the first demonstration of a continuous-wave
      optical parametric oscillator (OPO) based on periodically poled KTiOPO(4) . The
      10-mm-long flux-grown crystal had a quasi-phase-matched period of 9mum . The pump
      source was a miniature frequency-doubled Nd:YAG laser, and the threshold power of
      this doubly resonant device was 51 mW. The OPO was operated near room
      temperature. The signal and the idler wavelengths could be tuned in the range
      1037-1093 nm by variation of the crystal temperature (32-38 degrees C) and the
      cavity length. Unlike in other nonlinear crystals, green-induced infrared
      absorption was not observed up to the highest pumping intensity of approximately
      4.5kW/cm(2) .

PMID- 18091900
TI  - Energy transfer coupling of two-photon absorption and reverse saturable
      absorption for enhanced optical power limiting.
AB  - We introduce a new approach to enhancing the optical power-limiting function at
      near-IR wavelength (~800 nm) by coupling effective two-photon absorption in one
      molecule with excited-state absorption in another molecule. We experimentally
      demonstrate this approach by using a strong two-photon absorbing dye, AF-380, and
      a strong reverse saturable absorber, C(60) . A nanosecond time-resolved
      experiment is used to show that energy transfer from AF-380 to C(60) generates
      triplet excitation in C(60) that further absorbs the pump beam to enhance the
      power-limiting function.

PMID- 18091901
TI  - Single-shot two-photon exposure of commercial photoresist for the production of
      three-dimensional structures.
AB  - We report the use of an amplified femtosecond laser for single-shot two-photon
      exposure of the commercial photoresist SU-8. By scanning of the focal volume
      through the interior of the resist, three-dimensional (3-D) structures are
      fabricated on a shot-by-shot basis. The 800-nm two-photon exposure and damage
      thresholds are 3.2 and 8.1TW/cm(2), respectively. The nonlinear nature of the two
      photon process allows the production of features that are smaller than the
      diffraction limit. Preliminary results suggest that Ti:sapphire oscillators can
      achieve single-shot two-photon exposure with thresholds as low as 1.6TW/cm(2) at
      700 nm, allowing 3-D structures to be constructed at megahertz repetition rates.

PMID- 18091902
TI  - Method of achieving phase delay with wide optical bandwidth in multimode
      interference devices.
AB  - A completely passive method of achieving phase delays inside multimode
      interference devices is presented. The desired relative phase is obtained by
      adjustment of the width of the waveguides in conjunction with the tapers to avoid
      interference inside the multimode section. One can generally apply the delay
      lines to avoid the use of active elements, and they are less sensitive to changes
      in wavelength than the traditional method with bends. Using this method, we have
      designed and analyzed a zero-to-one mode converter. The converter exhibits
      minimum excess loss of 0.100 and 0.102 for TE and TM polarization, respectively.
      A very large 1-dB bandwidth exceeding 350 nm is achieved.

PMID- 18091903
TI  - Photosensitivity of lead germanate glass waveguides grown by pulsed laser
      deposition.
AB  - We report very large photoinduced refractive-index changes Dn, of the order of
      ~10(2), in lead germanate glass waveguides grown by pulsed-laser deposition. The
      magnitude of Dn was derived from measurements of diffraction efficiency for
      gratings written by exposure to 244-nm light through a phase mask, whereas the
      sign of Dn was determined from ellipsometric data. Results are shown for films
      grown under oxygen pressures ranging from 1 chi 10(-2) to 6 chi 10(-2)mbars
      (1.33mbars=1 Torr).

PMID- 18091904
TI  - Two-color facility based on a broadly tunable infrared free-electron laser and a
      subpicosecond-synchronized 10-fs-Ti:sapphire laser.
AB  - Subpicosecond synchronization between a mirror-dispersion-controlled 10-fs
      Ti:sapphire laser and the Free-Electron Laser for Infrared Experiments has been
      achieved. The measured intensity cross correlation between the two lasers is
      consistent with a jitter of only 400 fs rms. The wide and continuous tunability
      of the free-electron laser (FEL; 4.2-300mum) combined with ultrashort pulse
      duration of six optical cycles and high pulse energy of several tens of
      microjoules makes a series of two-color experiments possible in a previously
      inaccessible wavelength range. We demonstrate these capabilities by performing a
      two-color pump-probe experiment to study carrier cooling in GaAs. A FEL tuned
      from 8 to 17mum is used as the pump, and a synchronized Ti:sapphire laser pulse
      serves as the probe.

PMID- 18091905
TI  - 2-W Ho:YAG laser intracavity pumped by a diode-pumped Tm:YAG laser.
AB  - Efficient room-temperature operation of a Ho:YAG laser, intracavity pumped by a
      diode-bar-pumped Tm:YAG laser, is reported. At rod mount temperatures of 10
      degrees C, for both the Tm:YAG and the Ho:YAG rods, we obtained 2.1 W of output
      at 2.097mum from the Ho:YAG laser for 9.2 W of diode power incident upon the
      Tm:YAG rod.

PMID- 18091906
TI  - All-solid-state generation of 100-kHz tunable mid-infrared 50-fs pulses in type I
      and type II AgGaS(2).
AB  - We report the operation of an all-solid-state system for the generation of
      tunable mid-infrared sub-50-fs pulses. A Ti:sapphire regenerative amplifier,
      pumped by 10 W of power from 532-nm, diode-pumped, frequency-doubled Nd:YVO(4)
      lasers, produced 4-muJ energy, sub-50-fs pulses at 800 nm with a 100-kHz
      repetition rate. This output was used to drive a beta-BaB(2)O(4) optical
      parametric amplifier followed by a difference-frequency generator based on a
      AgGaS(2) crystal. Continuous tuning of ultrafast pulses from 2.4m to longer than
      12mum was obtained. A performance comparison of difference-frequency generation
      in type I and type II phase-matched AgGaS(2) is reported.

PMID- 18091907
TI  - 30-fs, cavity-dumped optical parametric oscillator.
AB  - We demonstrate cavity dumping of a synchronously pumped optical parametric
      oscillator (OPO). The OPO delivers 30-fs pulses with energies as high as 13 nJ at
      up to 400-kHz repetition rates. The OPO's tunability ranges from 570 to 600 nm
      and is limited by the resonator mirror coatings. The time jitter between pulses
      of a Ti:sapphire laser and the cavity-dumped OPO pulses is smaller than 30 fs,
      permitting multicolor time-resolved spectroscopic experiments.

PMID- 18091908
TI  - Semiconductor-doped-silica saturable-absorber films for solid-state laser mode
      locking.
AB  - We describe a new saturable-absorber materials system for solid-state laser mode
      locking based on thin, nonepitaxially grown, semiconductor-doped films. We
      fabricated thin films of InAs semiconductor microcrystalites in silica, using rf
      sputtering. We could control the linear absorption by varying the film thickness,
      and the nonlinear absorption saturation cross section and recovery time could be
      adjusted by use of rapid thermal annealing. The use of 30-nm- thick InAs-doped
      silica films on sapphire for initiation of Kerr-lens mode locking in a
      Ti:Al(2)O(3) laser was demonstrated. Pulses as short as 25 fs were generated with
      a wavelength tuning range from 800 to 880 nm.

PMID- 18091909
TI  - Optical image correlator realized with a hybrid liquid-crystal-photoconducting
      polymer structure.
AB  - A joint Fourier-transform optical correlator for image recognition based on a
      novel hybrid photoconducting polymer-nematic liquid-crystal structure is
      described. The optically addressed active element that we have designed is
      capable of performing real-time image processing 20 times/s, at light-intensity
      levels of 10mW/cm(2) with dc operating voltage of the order of 10 V. We present
      the results of correlation of simple objects as well as complicated photographs.
      The sensitivity, durability, and reliability of the presented system open
      possibilities for many applications.

PMID- 18091910
TI  - Topometry for locally changing materials.
AB  - Three-dimensional topometry is supplemented with ellipsometric measurements on
      the same pixel raster for calculation of the phase of the reflected waves and
      correction of the height fields. Lateral resolution is <1mum . The ellipsometric
      angles are determined by phase shifting and contrast evaluation. Three
      dimensional fields of the ellipsometric angles, the real and the imaginary parts
      of the refractive index, and the corrected topography of the heights are
      presented.

PMID- 18091911
TI  - Generation of coherent optical radiation by electronic means: the electro-optical
      parametric oscillator.
AB  - We describe a novel external light control element that is capable of stabilizing
      both the amplitude and the frequency of an optical input field. A demanding
      application of this electro-optical parametric oscillator, conversion of
      incoherent inputs into coherent, phase-trackable outputs with small residual
      intensity modulation, is reported. Estimations show that commercially available
      light-emitting diodes have the potential to act as pump sources, although the
      incoherent optical input field used in these initial experiments was prepared by
      filtering of the coherent emission of a laser diode.

PMID- 18091912
TI  - Spectroscopic temperature determination of aluminum monoxide in laser ablation
      with 266-nm radiation.
AB  - We report time-resolved measurements of diatomic aluminum monoxide spectra in the
      study of laser ablation by the use of frequency-quadrupled 266 nm Nd:YAG laser
      radiation. Spectroscopic temperatures of 3432(35) K and 3329(13) K are obtained
      at a delay time of 20mu, respectively, by the use of the modified diatomic
      Boltzmann plot and by the use of the Nelder-Mead algorithm in the fitting of the
      recorded spectrum.

PMID- 18091913
TI  - Reflection-type confocal readout for multilayered optical memory.
AB  - We present a multilayered optical memory for use in reading data with a confocal
      reflection microscope system. We use a recording medium in which photosensitive
      thin films and nonphotosensitive transparent films are stacked alternately. Since
      the photosensitive films are thinner than the depth of focus of the recording
      beam, the spatial frequency distribution of the recorded bit data is extended in
      the axial direction. The extended distribution overlaps the coherent optical
      transfer function of the reflection-type confocal microscope. Urethane-urea
      copolymer film is used as a photosensitive material. The recording and reading of
      two layers are demonstrated.

PMID- 18091914
TI  - Simple method for the complete characterization of an optical pulse.
AB  - A novel and simple method to measure the amplitude and the phase of optical
      pulses is presented. The technique basically involves modulating the optical
      pulse train in a particular manner and then directly examining the resultant
      optical spectrum. This experimental measurement technique, which is extremely
      accurate and sensitive and can be implemented with an all-fiber setup, permits
      direct measurement of the phase of the optical signal in the frequency domain.
      Experimental results demonstrate the use of this measurement technique for
      characterizing optical pulses at 10 GHz from a gain-switched laser diode.

PMID- 18091915
TI  - Observation of azimuthal modulation instability and formation of patterns of
      optical solitons in a quadratic crystal: errata.

PMID- 18091916
TI  - Nonmechanical grating-generated scanning coherence microscopy.
AB  - A novel method of coherence microscopy with a grating-generated delay line is
      demonstrated to produce depth-lateral images without axial or lateral scanning. A
      new image-reconstruction approach based on random phase modulation of the
      reference beam is realized. The depth-lateral reflections of test objects are
      digitally reconstructed with a simple algorithm.

PMID- 18091917
TI  - Surface profilometry based on polarization analysis.
AB  - We report a novel algorithm for the analysis of interferometric images for
      surface profiling. The algorithm can be used with any interferometric system in
      which the two interfering beams are orthogonally polarized. The algorithm is
      based on a measurement of the polarization state and gives a unique value for the
      path difference that is not subject to the ambiguities associated with fringe
      counting or phase unwrapping. A detector array allows the polarization state and
      hence the height of every pixel in the image to be determined simultaneously. The
      concept is easily extended to enable one to obtain the profiles of moving
      surfaces from a single pulse of illumination.

PMID- 18091918
TI  - Dependence of focal shift on Fresnel number and angular aperture.
AB  - The effect of angular aperture on the focal shift in optical systems of finite
      Fresnel number is considered. It is shown that the focal shift for a given
      Fresnel number decreases with increasing angular aperture.

PMID- 18091920
TI  - Spontaneous formation of symbiotic solitary waves in a backward quasi-phase
      matched parametric oscillator.
AB  - We show analytically the existence of nondegenerate symbiotic solitary waves in
      quadratic media with absorption losses. We study these new solitary waves in the
      particular case of a backward quasi-phase-matching configuration. Our numerical
      simulations reveal that, when it is used inside a singly resonant optical
      parametric oscillator, this configuration leads to the spontaneous formation of
      new solitary waves.

PMID- 18091919
TI  - Cooperative stimulated Brillouin and Rayleigh backscattering process in optical
      fiber.
AB  - We observed an unusually narrow spectrum of Stokes field and Gaussian statistics
      of Stokes power for the stimulated Brillouin scattering (SBS) process in 300-m
      single-mode optical fiber with high Rayleigh losses. The measured characteristics
      of the Stokes radiation indicate that SBS lasing took place in the fiber. The
      effect is explained as the result of dynamic distributed feedback that is due to
      double Rayleigh scattering (RS) of the Stokes field. The results of numerical
      simulation of the cooperative SBS-RS process in fiber are in good agreement with
      experimental results.

PMID- 18091921
TI  - Electronic and nuclear contributions to the third-order nonlinear optical
      susceptibilities of new p-N, N'-dimethylaniline tetrathiafulvalene derivatives.
AB  - We report large third-order nonlinear optical susceptibilities (?3?)(ijkl) of new
      tetrathiafulvalene derivatives, using the degenerate four-wave mixing (DFWM)
      method. To understand the physical nature of the optical nonlinearities, we
      separate their electronic and nuclear contributions. The electronic contribution
      to the third-order nonlinear optical susceptibilities of the molecules turns out
      to be dominant. From DFWM measurements we also deduce the values of the second
      order hyperpolarizabilities gamma, which are ~10(5) greater than the gamma value
      of CS(2).

PMID- 18091922
TI  - Oscillating dark cavity solitons.
AB  - We show that oscillating dark solitons exist on a stable continuous plane-wave
      background in a cavity with a saturable defocusing nonlinearity. These
      oscillations can be attributed to a linear internal mode of the soliton with a
      complex eigenvalue emerging above a definite input field intensity. Using a
      simple analytical model, we find that the self-oscillations appear as a
      consequence of an interaction between the center of the soliton and the
      surrounding ring.

PMID- 18091923
TI  - Electrode geometries for periodic poling of ferroelectric materials.
AB  - We have realized novel electrode configurations for efficient periodic poling of
      ferroelectric crystals by applying a simple patterning method based on laser
      induced material ablation. The new geometries were theoretically investigated and
      compared with conventional configurations. A systematic optimization of the
      patterning according to the ablated profile led to high-quality quasi-phase
      matched structures in lithium niobate with a grating period of 20 mum . The
      periodically poled samples were characterized by use of third-order second
      harmonic generation of a Nd:YAG laser.

PMID- 18091925
TI  - Analysis of optically amplified mid-infrared parametric generation in AlGaAs
      waveguides.
AB  - Based on the recent breakthroughs in oxidized AlGaAs technology, a considerable
      improvement in IR generation through merging of optical amplification and three
      wave mixing is predicted. Amplification of one of the two input fields is shown
      to strongly relax the phase-matching condition for difference-frequency
      generation in AlGaAs waveguides. This effect is potentially crucial for the
      realization of an integrated semiconductor optical parametric oscillator.

PMID- 18091924
TI  - Nonparaxiality stabilizes three-dimensional soliton beams in Kerr media.
AB  - On the basis of simple physical arguments involving energy flows and power
      invariants, we show that nonparaxiality stabilizes (1+2D) soliton beams in Kerr
      media.

PMID- 18091926
TI  - Fabrication and characterization of single-mode electro-optic polymer optical
      fiber.
AB  - We report on what we believe is the first demonstration of single-mode polymer
      optical fiber with embedded electrodes. We show that the electrodes can be used
      to pole the dye-doped core and to electro-optically phase modulate the light in
      the waveguide.

PMID- 18091927
TI  - Buildup of terahertz vector dark-soliton trains from induced modulation
      instability in highly birefringent optical fiber.
AB  - We present the experimental observation of generation of vector dark-soliton
      pulse trains with terahertz repetition rates in the normal dispersion regime of
      an optical fiber. The polarization solitons build up from induced cross-phase
      modulation instability of two orthogonal pumps in a highly birefringent fiber.

PMID- 18091928
TI  - Photon statistics of amplified spontaneous emission noise in a 10-Gbit/s
      optically preamplified direct-detection receiver.
AB  - We verify experimentally, over a dynamic range of 55 dB in the probability
      distribution, that the amplified spontaneous emission noise of the 0's from an
      optically preamplified receiver is degenerate Bose-Einstein distributed. Using
      the noise parameters extracted from the experiment, we are able to predict the
      sensitivity of a 10-Gbit/s direct-detection receiver.

PMID- 18091929
TI  - Frustration of Bragg reflection by cooperative dual-mode interference: a new mode
      of optical propagation.
AB  - A new optical mode of propagation is described, which is the natural eigenmode
      (supermode) of a fiber (or any optical waveguide) with two cospatial periodic
      gratings. The mode frustrates the backward Bragg scattering from the grating by
      destructive interference of its two constituent submodes (which are eigenmodes of
      a uniform waveguide). It can be used in a new type of spatial mode conversion in
      optical guides.

PMID- 18091930
TI  - Dual-wavelength continuous-wave cascade oscillation at 3 and 2 mum with a holmium
      doped fluoride-glass fiber laser.
AB  - We have demonstrated dual-wavelength continuous-wave oscillation at 3 and 2 mum
      with a Ho-doped ZrF(4)- BaF(2)- LaF(3)- AlF(3)- NaF fluoride-glass fiber laser by
      use of a cascade oscillation scheme. We have shown that the fiber laser operates
      with a high slope efficiency of 52% (at 3 and 2microm) with respect to the
      absorbed pump power. With a 6.5-m-long fiber we achieved an output power of 90 mW
      at each of the wavelengths that was limited only by the pump power, and the 3
      microm output power is to our knowledge higher than any previously reported level
      with 3-mum Ho(3+) -doped fiber lasers.

PMID- 18091931
TI  - High-power 100-fs pulse generation by frequency doubling of an erbium ytterbium
      fiber master oscillator power amplifier.
AB  - Frequency doubling of an erbium-ytterbium-fiber master-oscillator-power-amplifier
      system is demonstrated. Simultaneous amplification and pulse compression in
      multimode erbium-ytterbium-doped fibers produces high-quality near-diffraction
      and near-bandwidth-limited 100-fs pulses at a wavelength of 1.62microm with an
      average power of 230 mW at a repetition rate of 52 MHz. Periodically poled
      LiNbO(3) allows for frequency doubling with a conversion efficiency of 51%,
      producing near-bandwidth-limited 105-fs pulses with an average power of 117 mW
      and a pulse energy of 2.3 nJ at a wavelength of 810 nm.

PMID- 18091932
TI  - Rapid ultrafine-tunable optical delay line at the 1.55-mum wavelength.
AB  - A fast, ultrafine-tunable delay line at 1550 nm is demonstrated by use of acousto
      optic pulse shaping. Delays of up to 30 ps can be achieved without any optical
      readjustment. The delay is linear to the rf center frequency applied to the
      acousto-optic modulator and is fully electronic. It takes only 3micros to switch
      between different time slots, irrespective of the time separation in the tuning
      range of 30 ps; for a smaller tuning range the tuning speed can be faster. The
      tuning resolution and range depend on the choice of system parameters. The pulse
      energy can be regulated by rf power.

PMID- 18091933
TI  - Record low-power all-optical semiconductor switch operation at ultrafast
      repetition rates above the carrier cutoff frequency.
AB  - The switch repetition-rate limit of all-optical semiconductor switches, for which
      the dynamic extinction ratio decreases with increasing repetition rate, is
      examined and overcome. The extinction ratio is improved by optimization of the
      interferometer phase bias, which has previously been set to pi. The extinction
      ratio increase accompanies a drastic change in the output pulse spectrum. Both
      the output pulse profiles and the spectra, before and after optimization, are
      successfully reproduced by simulation. As a result, switch repetition of 42 GHz
      (2.5 times higher than the semiconductor-carrier cutoff frequency) is achieved by
      use of 5-ps, 1548-nm pump pulses. What are believed to be record low input pump
      pulse energies of 750 aJ (peak power, 140microW) at 10 GHz and 6 fJ (1.1 mW) at
      42 GHz are used.

PMID- 18091934
TI  - Dynamic wave-front generation for the characterization and testing of optical
      systems.
AB  - We describe a simple method for generating known optical aberrations dynamically,
      using a ferroelectric liquid-crystal spatial light modulator. Aberrations
      inherent in the optical system are measured and corrected, and as an example
      Kolmogorov turbulence is simulated for aperture sizes D/r(0) from 0 to 30,
      varying at frame rates up to 2.5 kHz. A measure of wave-front generation
      efficiency is introduced and is shown to be better than 86% for Kolmogorov phase
      screens with D/r(0) in the range from 0 to 30.

PMID- 18091935
TI  - Quantum noise in a continuous-wave laser-diode-pumped Nd:YAG linear optical
      amplifier.
AB  - We present measurements of the power noise that is due to optical amplification
      in a laser-diode-pumped Nd:YAG free-space traveling-wave linear amplifier in a
      master-oscillator-power-amplifier configuration. The quantum noise behavior of
      the optical amplifier was demonstrated by use of InGaAs photodetectors in a
      balanced detection configuration, at a total photocurrent of 100 mA and in a
      frequency band from 6.25 to 15.625 MHz. The experimental results are in good
      agreement with predictions.

PMID- 18091936
TI  - Elimination of cross talk in waveguide intersections.
AB  - We present general criteria for crossing perpendicular waveguides with nearly
      100% throughput and 0% cross talk. Our design applies even when the waveguide
      width is of the order of the wavelength. The theoretical basis for this
      phenomenon is explained in terms of symmetry considerations and resonant
      tunneling and is then illustrated with numerical simulations for both a two
      dimensional photonic crystal and a conventional high-index-contrast waveguide
      crossing. Cross-talk reduction by up to 8 orders of magnitude is achieved
      relative to unmodified crossings.

PMID- 18091937
TI  - Hollow-fiber delivery of high-power pulsed Nd:YAG laser light.
AB  - We propose hollow fibers for delivery of high-peak-power pulsed Nd:YAG laser
      light. Hollow fibers with an internal polymer layer were fabricated by a liquid
      phase coating technique. We reduced the losses of the fibers in the near-infrared
      region by producing a silver film that was very smooth owing to use of an
      ultrasonic wave for mixing of the silver and the reducer solutions in the silver
      plating process. The straight losses of the 1-m-long polymer-coated fibers were
      0.3 dB for the 700-mum bore size and 0.1 dB for the 1000-mum bore fiber.

PMID- 18091938
TI  - 5-GHz repetition-rate dual-wavelength pulse-train generation from an intracavity
      frequency-modulated Er-Yb:glass laser: errata.
AB  - In our recent Letter,(1) the affiliation of the authors was incorrect and should
      read as shown above. On p. 1549, in line 19 of the left-hand column the word
      "pulse" should be replaced with "trace." Finally, in Ref. 11 the name of the
      first author was misspelled. The correct reference should read as follows:

PMID- 18091939
TI  - Interference of traveling nondiffracting beams.
AB  - We study numerically the interference resulting from the superposition of two
      Bessel beams propagating in free space. We discuss how to obtain such beams and
      show the existence of the self-imaging effect during propagation. The evolution
      of the superimposed Bessel beams is analyzed on the basis of the evolution of the
      individual beams. Our exact numerical predictions contradict previous
      approximated analytical treatments, showing that they can lead to quantitatively
      wrong results and misleading conclusions.

PMID- 18091940
TI  - Measurements of complex third-order optical susceptibility in a collinear pump
      probe experiment.
AB  - We demonstrate simultaneous measurement of the real and the imaginary parts of
      third-order susceptibilities by use of a collinear pump-probe technique. This
      technique allows for good results and simple implementation. The signal analysis
      is based on the particular oscillatory signature versus the pump-probe delay
      allowed by the collinear configuration. Results are compared with interferometric
      measurements of a SF59 (Schott) glass sample.

PMID- 18091941
TI  - Beam amplification resulting from non-Bragg wave mixing in photorefractive
      strontium barium niobate.
AB  - Two-wave mixing with a small angle between beams in a photorefractive crystal
      biased with an external electric field leads to the formation of additional non
      Bragg orders and to wave amplification. A steady-state gain of 25 cm (-1) was
      obtained for an external voltage of 3 kV/cm in strontium barium niobate. Noise
      amplification and oscillation are also demonstrated.

PMID- 18091942
TI  - Waveguide second-harmonic generation device with broadened flat quasi-phase
      matching response by use of a grating structure with located phase shifts.
AB  - We report on a theoretical analysis and experiments for bandwidth broadening in
      quasi-phase-matched (QPM) second-harmonic generation (SHG).We used phase-shifted
      segments of a periodic grating to obtain a spectrally broadened, nearly flat
      response simultaneously with high conversion efficiency. We used an x-cut
      MgO:LiNbO(3) QPM waveguide in our analysis and experiments. The spectral range of
      the 850-nm fundamental for which SHG conversion exceeded 0.95 of the maximum
      value broadened from 0.02 to 0.12 nm when a 1-cm-long grating was divided into
      three segments with optimum phase shift. SHG conversion efficiency was 300%/W for
      this waveguide. The SHG efficiency and phase-matching characteristics showed good
      agreement with theoretical results.

PMID- 18091943
TI  - Ultraviolet generation by first-order frequency doubling in periodically poled
      KTiOPO(4).
AB  - First-order quasi-phase-matched frequency doubling at 780 nm in a 1-mm-thick
      periodically poled KTiOPO(4) crystal with an inverted-domain period of 2.95
      microm has been demonstrated for the first time to the authors' knowledge. A
      normalized conversion efficiency of 1.1%W(-1) cm(-1) has been obtained in cw
      mode. Experiments show that group-velocity walk-off prevents efficient frequency
      doubling of femtosecond pulses in KTiOPO(4) in the UV spectral range. However,
      because of the large optical nonlinearity, periodically poled structures can be
      efficiently used for frequency doubling of cw and pulsed lasers with pulse
      lengths as short as ~1 ps .

PMID- 18091944
TI  - Periodically poled lithium niobate optical parametric amplifier seeded with the
      narrow-band filtered output of an optical parametric generator.
AB  - The results of a simple scheme to generate continuously tunable pulsed narrow
      bandwidth (less than 0.1 cm (-1)) light in the infrared are presented. A
      periodically poled lithium niobate (PPLN) optical parametric amplifier is seeded
      with the filtered output of a PPLN optical parametric generator. A high-finesse
      Fabry-Perot etalon is used as the filtering element, giving bandwidths as narrow
      as 0.08 cm (-1) and tunable over 18 cm (-1) without any adjustments to the PPLN
      crystals. High efficiency is obtained with a 15-ns 1-kHz Nd:YAG laser, giving
      energies of up to 180 microJ of signal at 1.6 microm and 60 microJ of idler at
      3.3 microm .

PMID- 18091945
TI  - Doubly resonant continuous-wave optical parametric oscillator pumped by a single
      mode diode laser.
AB  - The performance characteristics of a doubly (signal and idler) resonant
      continuous-wave optical parametric oscillator based on periodically poled lithium
      niobate and pumped by a 100-mW single-mode laser diode at 810 nm are reported.
      Pump power thresholds as low as 16 mW and wavelength tuning over the range 1.15
      1.25 microm at the signal and 2.31-2.66 microm at the idler were achieved through
      variation of crystal temperature, pump wavelength, and grating period. Up to 5 mW
      of signal output was obtained with the single-mode diode pump, and signal powers
      of up to 39 mW were obtained when pumping with a 400-mW injection-locked broad
      area diode laser.

PMID- 18091946
TI  - Stoichiometric Mg:LiNbO(3) as an effective material for nonlinear optics.
AB  - Photorefractive damage, optical absorption, photoconductivities, and
      photogalvanic currents of stoichiometric LiNbO(3) single crystals with different
      Mg doping levels have been investigated. Nominally pure stoichiometric LiNbO(3)
      shows lower photorefractive damage resistance than congruent crystal; however,
      stoichiometric crystals doped with MgO of more than 1.8 mol. % exhibit no
      measurable photorefractive damage at 532 nm to intensities of as much as 8
      MW/cm(2) . This remarkable damage resistance can be attributed not only to
      increased photoconductivity but also to decreased photogalvanic current.
      Stoichiometric Mg:LiNbO(3) also demonstrates the shortest absorption edge, 302
      nm, and a single-domain nature with low scattering losses.

PMID- 18091947
TI  - Low-pump-threshold continuous-wave singly resonant optical parametric oscillator.
AB  - We describe a compact all-solid-state continuous-wave singly resonant optical
      parametric oscillator (SRO) with a minimal pump-power requirement. The SRO is
      based on periodically poled LiNbO(3) as the nonlinear material and is pumped by a
      1-W diode-pumped Nd:YVO(4) minilaser at 1.064 microm . By exploiting the
      intracavity pumping technique in a 50-mm crystal, we have achieved SRO operation
      threshold at a diode pump power of only 310 mW.At 1 W of input diode power, the
      SRO delivers 70 mW of output power in the nonresonant idler at 3.66 microm , at a
      photon conversion efficiency of 55%. Multiparameter tuning of the SRO yields a
      signal wavelength range from 1.45 to 1.60 microm and an idler wavelength range
      from 3.16 to 4.02 microm in the mid infrared. The device is characterized by
      robust turnkey operation and long-term amplitude-stable performance.

PMID- 18091949
TI  - Instability of dispersion-managed solitons in a system with filtering.
AB  - Unstable behavior of dispersion-managed (DM) solitons in a system with lumped
      filtering is numerically studied. A variational analysis shows that the system
      cannot have stable fixed DM soliton solutions when the filter location is
      improperly chosen. This is because of the unique dynamics of the spectral
      behavior of DM solitons, which differs from that of standard solitons in fibers
      with constant dispersion. The instability is confirmed by numerical simulations
      with and without sliding center frequencies of the filters.

PMID- 18091948
TI  - High-temperature stable gratings in germanosilicate planar waveguides.
AB  - Negative index gratings in planar germanosilicate waveguides were found to be
      stable up to 500 degrees C. The annealing properties are similar to those of
      negative index fiber gratings.

PMID- 18091950
TI  - Are low-loss glass ceramic optical waveguides possible?
AB  - The results of a cutback measurement of a glass-ceramic optical waveguide with
      single-mode fiber geometry have demonstrated that sub decibels per kilometer
      losses can be achieved. Difference spectra show that the limit of intrinsic
      scattering in these two-phase structures ought to be tens of decibels per
      kilometer.

PMID- 18091951
TI  - Simple high-coherence rapidly tunable external-cavity diode laser.
AB  - We describe a simple electro-optically activated external-cavity diode laser
      designed to provide high-speed, high-coherence tuning over gigahertz frequency
      ranges. Tuning as fast as 23 GHz/ micros is demonstrated. Coherence measurements
      indicate transform-limited quiescent laser linewidth in observation windows as
      wide as ~100 micros and transform-limited chirps. A self-heterodyne, cross
      correlation-based coherence diagnostic is developed for characterizing phase
      coherence during high-speed chirps.

PMID- 18091952
TI  - Fractal structure of eigenmodes of unstable-cavity lasers.
AB  - We show that the eigenmodes of unstable-cavity lasers have fractal structure, in
      contrast with the well-known stable-cavity eigenmodes. As with all fractals, the
      dynamic range over which self-similarity holds is limited; in this case the range
      is set by diffraction, i.e., by the Fresnel number of the resonator. We determine
      the fractal dimension of the mode profiles and show that it is related to the
      aperture shape.

PMID- 18091953
TI  - Tunable polarization response of a planar asymmetric-spiral infrared antenna.
AB  - We present measurements at 10.6 microm that demonstrate electronic tuning of the
      polarization response of asymmetric-spiral infrared antennas connected to Ni-NiO
      Ni diodes. Continuous variation of the bias voltage applied to the diode results
      in a rotation of the principal axis of the polarization ellipse of the spiral
      antenna. A 90 degrees tuning range is measured for a bias voltage that varies
      from -160 to +160 mV .This effect is caused by a small asymmetry of the deposited
      diode contact or by a variation of the detector capacitance with the applied bias
      voltage.

PMID- 18091954
TI  - Adaptive control of pulse phase in a chirped-pulse amplifier.
AB  - Using experimental feedback, we demonstrate that a chirped-pulse amplifier can
      adaptively learn to compensate for the higher-order phase dispersion that is
      inherent in the amplification process. A genetic algorithm-based search routine
      is used to repetitively update the pulse phase in a programmable pulse stretcher
      during a plasma breakdown experiment to maximize the magnitude of spectral
      blueshift. Reductions in pulse duration from 37 to 30 fs and substantially better
      wing structure are typically obtained as a result of the optimization.

PMID- 18091955
TI  - 54-fs, 1-GW, 1-kHz pulse amplification in Cr:forsterite.
AB  - 30-fs pulses at 1.22 microm are produced by a self-mode-locked Cr:forsterite
      laser and amplified in a Cr:forsterite regenerative amplifier by a chirped-pulse
      amplification technique. 54-fs, 1-GW pulses at a 1-kHz repetition rate are
      obtained.

PMID- 18091956
TI  - Excitation localization principle for spherical microcavities.
AB  - Van de Hulst's localization principle relates the principal mode number to the
      external beam position that maximizes energy coupling to a spherical cavity mode.
      Our experiments in lasing microdroplets verify localization but only for low- Q
      modes, when the cavity may be considered to be a nearly perfect homogeneous
      sphere. The principle fails in the perturbation-dominated high- Q limit.
      Surprisingly, near-surface resonances are still efficiently excited in these
      cases but require impact parameters slightly smaller than the sphere radius.
      Numerical modeling suggests that this new input channel depends on surface
      scattering.

PMID- 18091957
TI  - Reflection confocal microscope readout system for three-dimensional photochromic
      optical data storage.
AB  - We propose to use a reflection confocal microscope (RCM) as a readout system for
      digital data stored in a three-dimensional (3D) photochromic optical memory. We
      describe the merits and the difficulties for 3D optical memory that are
      associated with the use of such a RCM.It is shown by means of 3D Fourier space
      analysis that successful reading of 3D data can be obtained by selection of the
      appropriate parameter for the RCM.The system parameters include the numerical
      aperture of the objective lens and the wavelength of the light used for analysis
      (reading). Experimental results of multilayer recording and reflection confocal
      reading in photochromic-molecule-doped poly(methyl methacrylate) are presented.
      Good-contrast images are obtained.

PMID- 18091958
TI  - Incremental holographic recording in lithium niobate with active phase locking.
AB  - Angular-multiplexed hologram recording in iron-doped lithium niobate crystals was
      carried out with near-infrared light. An incremental recording schedule with
      active phase locking of the light pattern onto the hologram was used. Continuous
      and reproducible recording of holograms of equal efficiency was achieved, and a
      hologram multiplexing number, M/#=2 , for a 5-mm-thick crystal was obtained at a
      760-nm wavelength of light.

PMID- 18091959
TI  - Highly sensitive dynamic strain measurements by locking lasers to fiber Bragg
      gratings.
AB  - A novel, sensitive, simple, and robust strain interrogation technique is analyzed
      and experimentally tested. By locking a laser wavelength to the midreflection
      wavelength of a standard fiber Bragg grating and measuring the error signal, we
      achieve high dynamic strain sensitivity of 45 picostrain/ radicalHz rms at 3 kHz,
      where the dominant noise in the experiment is the laser frequency noise.

PMID- 18091960
TI  - Beam switching with binary single-order diffractive gratings.
AB  - A new type of a micro-optomechanical dielectric switch in free-space
      configuration for visible light is proposed and experimentally demonstrated. The
      combination of scalar and rigorous diffraction analysis of Gaussian beams
      predicts high high switching efficiency with a single/noise ratio of better than
      40 dB.

PMID- 18091961
TI  - Adjustable electro-optic microlens with two concentric ring electrodes.
AB  - A theoretical model of a new variable-focal-length lens design that uses an
      electro-optic wafer with two double-sided concentric ring electrodes is proposed
      on the basis of an original technique for calculating the induced refractive
      index. It is shown that the relationship between ring radii and wafer thickness
      produces the required distribution of the refractive index to create converging
      focusing elements.

PMID- 18091963
TI  - Diffusion of photoexcited azo dye in a liquid-crystal host: errata.

PMID- 18091962
TI  - Binary-phase zone-plate arrays based on hybrid solgel glass.
AB  - An organically modified silane zirconate-based solgel material is used for the
      fabrication of binary-phase zone-plate arrays. The synthesized hybrid solgel
      material has a negative tone under UV exposure and can be patterned by a UV
      lithography process. The transmittance of the material is nearly 100%, and the
      refractive index is 1.52. Two different diffractive lens arrays with focal
      lengths of 5 and 42 cm have been fabricated. The average roughness of the zone
      surface is less than 20 nm. The diffraction efficiencies of the lens arrays are
      measured as a function of modulation depth and exposure dose. A diffraction
      efficiency of 30% is achieved.

PMID- 18091964
TI  - Parameterization of the inherent optical properties of Murchison Bay, Lake
      Victoria.
AB  - Lake Victoria, Africa's largest freshwater lake, suffers greatly from negative
      changes in biomass of species of fish and also from severe eutrophication. The
      continuing deterioration of Lake Victoria's ecological functions has great long
      term consequences for the ecosystem benefits it provides to the countries
      bordering its shores. However, knowledge about temporal and spatial variations of
      optical properties and how they relate to lake constituents is important for a
      number of reasons such as remote sensing, modeling of underwater light fields,
      and long-term monitoring of lake waters. Based on statistical analysis of data
      from optical measurements taken during half a year of weekly cruises in Murchison
      Bay, Lake Victoria, we present a three-component model for the absorption and a
      two-component model for the scattering of light in the UV and the visible regions
      of the solar spectrum along with tests of their ranges of validity. The three
      component input to the model for absorption is the chlorophyll-a (Chl-a), total
      suspended materials concentrations, and yellow substance absorption, while the
      two-component input to the model for scattering is the Chl-a concentration and
      total suspended materials.

PMID- 18091965
TI  - Effects of image restoration on automatic acquisition of moving objects in
      thermal video sequences degraded by the atmosphere.
AB  - We aim to determine the effect of image restoration (deblurring) on the ability
      to acquire moving objects detected automatically from long-distance thermal video
      signals. This is done by first restoring the videos using a blind-deconvolution
      method developed recently, and then examining its effect on the geometrical
      features of automatically detected moving objects. Results show that for modern
      (low-noise and high-resolution) thermal imaging devices, the geometrical features
      obtained from the restored videos better resemble the true properties of the
      objects. These results correspond to a previous study, which demonstrated that
      image restoration can significantly improve the ability of human observers to
      acquire moving objects from long-range thermal videos.

PMID- 18091966
TI  - Near-field scattered by a single nanoslit in a metal film.
AB  - Using a scanning near-field optical microscope, we visualize, in three
      dimensions, the electromagnetic field distribution near an isolated slit aperture
      in a thin gold film. At the metal-air interface and for a TM incident
      polarization, we confirm some recently observed results and show that the slit
      generates two kinds of surface waves: a slowly decaying surface plasmon polariton
      and a quasi-cylindrical wave that decreases more rapidly when moving away from
      the slit. These waves are not generated for a TE incident polarization. In a
      noncontact mode, we also observe how the transmitted light diverges in free
      space. At a small distance from the slit (< 2 microm), we find that the emerging
      light spreads in all directions for TM, forming an electromagnetic cloud, whereas
      it is concentrated above the slit for TE, forming a more directive light jet. The
      experimental images are in good agreement with the numerical simulations.

PMID- 18091967
TI  - Strain sensitivity control of fiber Bragg grating structures with fused tapers.
AB  - We report on the analysis and experimental validation of the strain sensitivity
      dependences of a fiber Bragg grating written in standard optical fiber when
      combined with fused tapers. By controlling the difference between the cross
      sections of the fused taper and the Bragg grating, the strain sensitivity of the
      Bragg wavelength can be changed by acting on the gauge length. The strain sensing
      characteristics of an interferometric structure formed by fabricating a fused
      taper in the middle of a fiber Bragg grating are also reported.

PMID- 18091968
TI  - Ultrashort intense-field optical vortices produced with laser-etched mirrors.
AB  - We introduce a simple and practical method to create ultrashort intense optical
      vortices for applications involving high-intensity lasers. Our method utilizes
      femtosecond laser pulses to laser etch grating lines into laser-quality gold
      mirrors. These grating lines holographically encode an optical vortex. We derive
      mathematical equations for each individual grating line to be etched, for any
      desired (integer) topological charge. We investigate the smoothness of the etched
      grooves. We show that they are smooth enough to produce optical vortices with an
      intensity that is only a few percent lower than in the ideal case. We demonstrate
      that the etched gratings can be used in a folded version of our 2f-2f setup [Opt.
      Express 19, 7599 (2005)] to compensate angular dispersion. Finally, we show that
      the etched gratings withstand intensities of up to 10(12) W/cm(2).

PMID- 18091969
TI  - Flexible depth-of-field imaging system using a spatial light modulator.
AB  - A major problem of optical microscopes is their small depth-of-field (DOF), which
      hinders automation of micro object manipulation using visual feedback. Wavefront
      coding, a well-known method for extending DOF, is not suitable for direct
      application to micro object manipulation systems based on visual feedback owing
      to its expensive computational cost and due to a trade-off between the DOF and
      the image resolution properties. To solve such inherent problems, a flexible DOF
      imaging system using a spatial light modulator in the pupil plane is proposed.
      Especially, the trade-off relationship is quantitatively analyzed by experiments.
      Experimental results show that, for low criterion resolution, the DOF increases
      as the strength of the mask increases, while such a trend was not found for high
      criterion resolution. With high criterion resolution, the DOF decreases as the
      mask strength increases when high-resolution images are required. The results
      obtained can be used effectively to find the optimum mask strength given the
      desired image resolution.

PMID- 18091970
TI  - Sizing of irregular particles using a near backscattered laser Doppler system.
AB  - A near backscattered laser Doppler system was presented to carry out velocity and
      size distribution measurements for irregular particles in two-phase flows. The
      technique uses amplitudes of particles Doppler signals to estimate the particle
      size distribution in a statistical manner. Holve's numerical inversion scheme is
      employed to unfold the dependence of the scattered signals on both particle
      trajectory and orientation through the measurement volume. The performance and
      error level of the technique were simulated, and several parameters including the
      number of particle samples, the fluctuation of irregular particle response
      function, inversion algorithms, and types of particle size distribution were
      extensively investigated. The results show that the size distributions for those
      irregular particles even with strong fluctuations in response function can be
      successfully reconstructed with an acceptable error level using a Phillips-Twomey
      non-negative least-squares algorithm instead of a non-negative least-squares one.
      The measurement system was then further experimentally verified with irregular
      quartz sands. Using inversion matrix obtained from the calibration experiment,
      the average measurement error for the mixing quartz sands with a size range of
      200-560 microm are found to be about 23.3%, which shows the reliability of the
      technique and the potential for it to be applied to industrial measurement.

PMID- 18091971
TI  - Apparatus designed for very accurate measurement of the optical reflection.
AB  - The described instrument is a new reflectometer designed to check the normal
      specular reflectance of 40,000 reflectors necessary for the Laser Megajoule
      (LMJ). This new reflectometer has a high accuracy over the 400-950 nm wavelength
      range and allows the delicate measurement of shaped parts. The measurements are
      relative and several reference mirrors, which are low loss dielectric mirrors
      [R(lambda)>99.9%], are used for the standardization. The apparatus gives an
      excellent repeatability (< 0.06% at 2sigma) thanks to its design and automatic
      focalization imaging system. After a brief review that is related to performance
      evolution of the spectrophotometers, our facility and its components are
      described. The methodology of focusing and calibration are explained. The
      capabilities of our device are illustrated through some measurements realized on
      flat or shaped samples.

PMID- 18091972
TI  - Multispectral method for skin imaging: development and validation.
AB  - A visible wide field multispectral system for comprehensive imaging of skin
      chromophores and blood vessels has been implemented, and an inhomogeneous Monte
      Carlo model of photon migration with randomly distributed blood vessels embedded
      in dermis has been developed. Predetermined nonlinear transforms have been
      obtained to address the nonlinear interdependent relationship among diffusive
      reflectance spectra, skin physiology properties, and geometry. For validation, in
      addition to real skin experiments and phantoms experiments, two alternative
      methods for blood vessel imaging have been used on the same set of subjects to
      compensate for the lack of ground truth for skin subsurface imaging.

PMID- 18091973
TI  - Determination of the particulate extinction-coefficient profile and the column
      integrated lidar ratios using the backscatter-coefficient and optical-depth
      profiles.
AB  - A new method is considered that can be used for inverting data obtained from a
      combined elastic-inelastic lidar or a high spectral resolution lidar operating in
      a one-directional mode, or an elastic lidar operating in a multiangle mode. The
      particulate extinction coefficient is retrieved from the simultaneously measured
      profiles of the particulate backscatter coefficient and the particulate optical
      depth. The stepwise profile of the column-integrated lidar ratio is found that
      provides best matching of the initial (inverted) profile of the optical depth to
      that obtained by the inversion of the backscatter-coefficient profile. The
      retrieval of the extinction coefficient is made without using numerical
      differentiation. The method reduces the level of random noise in the retrieved
      extinction coefficient to the level of noise in the inverted backscatter
      coefficient. Examples of simulated and experimental data are presented.

PMID- 18091974
TI  - OH absorption spectroscopy in a flame using spatial heterodyne spectroscopy.
AB  - We demonstrate measurements of OH absorption spectra in the post-flame zone of a
      McKenna burner using spatial heterodyne spectroscopy (SHS). SHS permits high
      resolution, high-throughput measurements. In this case the spectra span
      approximately 308-310 nm with a resolution of 0.03 nm, even though an extended
      source (extent of approximately 2x10(-7) m(2) rad(2)) was used. The high spectral
      resolution is important for interpreting spectra when multiple absorbers are
      present for inferring accurate gas temperatures from measured spectra and for
      monitoring weak absorbers. The present measurement paves the way for absorption
      spectroscopy by SHS in practical combustion devices, such as reciprocating and
      gas-turbine engines.

PMID- 18091975
TI  - Influence of binding layer on the reflective performance of a Au film in vacuum
      ultraviolet wavelength region.
AB  - We investigate the influence of the binding layer on the reflectance of a Au film
      in vacuum ultraviolet (VUV) wavelength region theoretically and experimentally.
      The reflectance of Au films on quartz glass substrates with an approximately 2 nm
      binding layer of Ti, Cr, and Ir are estimated and fabricated. Their reflectance
      in the 115-140 nm wavelength region are measured continuously by the
      reflectometer located in the National Synchroton Radiation Laboratory. The
      testing results show that the addition of the binding layer indeed greatly
      enhances the interfacial adhesion of the Au layer to the quartz glass substrate,
      but it also exerts a considerably adverse impact on the reflectance of the Au
      layer in VUV wavelength region. In near normal incidence, the reflectance of the
      Au layer with a 2 nm thick binding layer is less than 20%, approximately 5% lower
      than those without the binding layer. The material used for the binding layer has
      little impact on the reflectance if this layer is thin enough.

PMID- 18091976
TI  - Kinematic and deformation parameter measurement by spatiotemporal analysis of an
      interferogram sequence.
AB  - In recent years, optical interferometry has been applied to the whole-field,
      noncontact measurement of vibrating or continuously deforming objects. In many
      cases, a high resolution measurement of kinematic (displacement, velocity, and
      acceleration, etc.) and deformation parameters (strain, curvature, and twist,
      etc.) can give useful information on the dynamic response of the objects
      concerned. Different signal processing algorithms are applied to two types of
      interferogram sequences, which were captured by a high-speed camera using
      different interferometric setups: (1) a speckle or fringe pattern sequence with a
      temporal carrier and (2) a wrapped phase map sequence. These algorithms include
      Fourier transform, windowed Fourier transform, wavelet transform, and even a
      combination of two of these techniques. We will compare these algorithms using
      the example of a 1D temporal evaluation of interferogram sequences and extend
      these algorithms to 2D and 3D processing, so that accurate kinematic and
      deformation parameters of moving objects can be evaluated with different types of
      optical interferometry.

PMID- 18091977
TI  - Analytical extraction of leaky modes in circular slab waveguides with arbitrary
      refractive index profile.
AB  - Circular slab waveguides are conformally transformed into straight inhomogeneous
      waveguides, whereupon electromagnetic fields in the core are expanded in terms of
      Legendre polynomial basis functions. Thereafter, different analytical expression
      of electromagnetic fields in the cladding region, viz. Wentzel-Kramers-Brillouin
      solution, modified Airy function expansion, and the exact field solution for
      circular waveguides, i.e., Hankel function of complex order, are each matched to
      the polynomial expansion of the transverse electric field within the guide. This
      field matching process renders different boundary conditions to be satisfied by
      the set of orthogonal Legendre polynomial basis functions. In this fashion, the
      governing wave equation is converted into an algebraic and easy to solve
      eigenvalue problem, which is associated with a matrix whose elements are
      analytically given. Various numerical examples are presented and the accuracy of
      each of the abovementioned different boundary conditions is assessed.
      Furthermore, the computational efficiency and the convergence rate of the
      proposed method with increasing number of basis functions are briefly discussed.

PMID- 18091978
TI  - Microforging technique for rapid, low-cost fabrication of lens array molds.
AB  - Interest in micro-optical components for applications ranging from
      telecommunications to life sciences has driven the need for accessible, low-cost
      fabrication techniques. Many microlens fabrication processes are unsuitable for
      applications requiring 100% fill factor, apertures approximately 1000 microm with
      high numerical aperture, and scalability to large areas (e.g., tens of
      centimeters to meters) with millions of lenses. We report on a flexible, low-cost
      mold fabrication technique that utilizes a combination of milling and
      microforging. The technique involves first performing a rough cut with a ball-end
      mill. Final shape and sag height are then achieved by pressing a sphere of equal
      diameter into the milled divot. Using this process, we have fabricated molds for
      rectangular arrays of 1-10,000 lenses with apertures of 25-1600 microm, sag
      heights of 3-130 microm, interlens spacings of 250-2000 microm, and fill factors
      up to 100%. Mold profiles have a roughness and figure error of 68 nm and 354 nm,
      respectively, for 100% fill factor, 1000 microm aperture lenses. The required
      forging force was modeled as a modified open-die forging process and
      experimentally verified to increase nearly linearly with surface area. The
      optical performance of lens arrays injection molded from microforged molds was
      characterized by imaging the point spread function and was found to be in the
      range of theoretical values. The process can be easily adapted to lenticular
      arrays as well. Limitations include milling machine range and accuracy.

PMID- 18091980
TI  - Nuclear localization of HBD-1 in human keratinocytes.
AB  - OBJECTIVE: Human defensins and cathelicidins are a family of cationic
      antimicrobial peptides (AMPs), which play multiple roles in both innate and
      adaptive immune systems. They have direct antimicrobial activity against several
      microorganisms including burn pathogens. The majority of components of innate and
      adaptive immunity either express naturally occurring defensins or are otherwise
      chemoattracted or functionally affected by them. They also enhance adaptive
      immunity and wound healing and alter antibody production. All mechanisms to
      explain multiple functions of AMPs are not clearly understood. Prior studies to
      localize defensins in normal and burned skin using deconvolution fluorescence
      scanning microscopy indicate localization of defensins in the nucleus,
      perinuclear regions, and cytoplasm. The objective of this study is to further
      confirm the identification of HBD-1 in the nucleus by deconvolution microscopic
      studies involving image reconstruction and wire frame modeling. RESULTS: Our
      study demonstrated the presence of intranuclear HBD-1 in keratinocytes throughout
      the stratum spinosum by costaining with the nuclear probe DAPI. In addition, HBD
      1 sequence does show some homology with known cationic nuclear localization
      signal sequences. CONCLUSION: To our knowledge, this is the first report to
      localize HBD-1 in the nuclear region, suggesting a role for this peptide in gene
      expression and providing new data that may help determine mechanisms of defensin
      functions.

PMID- 18091979
TI  - Neuronal nitric oxide synthase contributes to the regulation of hematopoiesis.
AB  - Nitric oxide (NO) signaling is important for the regulation of hematopoiesis.
      However, the role of individual NO synthase (NOS) isoforms is unclear. Our
      results indicate that the neuronal NOS isoform (nNOS) regulates hematopoiesis in
      vitro and in vivo. nNOS is expressed in adult bone marrow and fetal liver and is
      enriched in stromal cells. There is a strong correlation between expression of
      nNOS in a panel of stromal cell lines established from bone marrow and fetal
      liver and the ability of these cell lines to support hematopoietic stem cells;
      furthermore, NO donor can further increase this ability. The number of colonies
      generated in vitro from the bone marrow and spleen of nNOS-null mutants is
      increased relative to wild-type or inducible- or endothelial NOS knockout mice.
      These results describe a new role for nNOS beyond its action in the brain and
      muscle and suggest a model where nNOS, expressed in stromal cells, produces NO
      which acts as a paracrine regulator of hematopoietic stem cells.

PMID- 18091981
TI  - Cement burns: the dublin national burns unit experience.
AB  - OBJECTIVE: Cement burns account for relatively few admissions to a burn unit;
      however, these burns deserve separate consideration because of special features
      of diagnosis and management. Cement burns, even though potentially disabling,
      have rarely been reported in literature. METHODS: A retrospective review was
      performed of all patients admitted with cement burns injuries to the national
      burns unit at the St James's Hospital in Dublin, Ireland, over a 10-year period
      for the years 1996-2005. RESULTS: A total of 46 patients with cement burns were
      admitted. The majority of patients were aged 16-74 years (mean age = 32 years).
      Eighty-seven percent of injuries occurred in an industrial and 13% in a domestic
      setting. The upper and lower extremities were involved in all the patients, and
      the mean total body surface area affected was 6.5%. The mean length of hospital
      stay was 21 days with a range of 1-40 days. Thirty-eight (82%) were surgically
      managed involving debridement and split-thickness skin graft (SSG) and four (9%)
      were conservatively managed. A further four did not have data available.
      CONCLUSION: Widespread inexperience in dealing with this group of cement burns
      patients and delays in referral to burns unit highlights the potential for
      greater levels of general awareness and knowledge in both prevention and
      treatment of these burns. As well, early debridement and split-thickness skin
      grafting at diagnosis constitutes the best means of reducing the high
      socioeconomic costs and allows for early return to work.

PMID- 18091982
TI  - Amnion-derived multipotent progenitor cells increase gain of incisional breaking
      strength and decrease incidence and severity of acute wound failure.
AB  - OBJECTIVE: Acute wound failure is a common complication following surgical
      procedures and trauma. Laparotomy wound failure leads to abdominal dehiscence and
      incisional hernia formation. Delayed recovery of wound-breaking strength is one
      mechanism for laparotomy wound failure. Early fascial wounds are relatively
      acellular, and there is a delay in the appearance of acute wound growth factors
      and cytokines. The objective of this study was to accelerate and improve
      laparotomy wound healing using amnion-derived multipotent cells (AMPs). AMPs'
      nonimmunogenic phenotype and relative abundance support its role as a cell
      therapy. METHODS: AMPs were injected into the load-bearing layer of rat abdominal
      walls prior to laparotomy, and cell viability was confirmed. Wound mechanical
      properties were measured over 28 days. The incidence and severity of laparotomy
      wound failure was measured in an incisional hernia model. RESULTS: AMP cells were
      viable in laparotomy wounds for at least 28 days and did not migrate to other
      tissues. Laparotomy wound-breaking strength was increased by postoperative day 7
      following AMP therapy. AMP therapy reduced the incidence of hernia formation and
      the size of hernia defects. Histology suggested stimulated wound fibroplasia and
      angiogenesis. CONCLUSIONS: AMP cell therapy reduces the incidence of laparotomy
      wound failure by accelerating the recovery of wound-breaking strength. This
      results in fewer incisional hernias and smaller hernia defects.

PMID- 18091983
TI  - Human keratinocytes cultured on collagen matrix used as an experimental burn
      model.
AB  - BACKGROUND: In experimental models in vivo, it is difficult to characterize the
      effect of thermal burns on epidermal keratinocytes. Since the response to thermal
      injury involves several systemic mechanisms, especially because of the stimulus
      to coagulation and inflammatory cascades, it becomes hard to evaluate the
      specific effect of thermal burns on keratinocytes. The aim of this study is to
      propose the use of human keratinocytes cultured on collagen matrix as an in vitro
      experimental burn model. METHODS: Human keratinocytes derived from neonatal
      foreskins were isolated and cultured following standard methods. All experiments
      used the same keratinocyte lineage and were carried out in triplicate. Initially,
      gels of collagen and Matrigel were prepared. For each gel, 2 x 10(6)
      keratinocytes were seeded and cultured to form stratified epithelia. Following,
      burn wounds were induced at 170 degrees C. RESULTS: Keratinocytes were cultured
      on collagen-coated Millicell membranes. Stratified epithelia were formed and
      burned on the seventh day after the cultures were raised to the air-liquid
      interface. The burn procedure is reproducible and can be easily executed.
      CONCLUSION: The proposed model can be used to study the effects of induced burn
      wounds on keratinocytes in a specific way.

PMID- 18091984
TI  - Sulfur mustard toxicity following dermal exposure: role of oxidative stress, and
      antioxidant therapy.
AB  - OBJECTIVE: Sulfur mustard (bis-2-(chloroethyl) sulfide) is a chemical warfare
      agent (military code: HD) causing extensive skin injury. The mechanisms
      underlying HD-induced skin damage are not fully elucidated. This review will
      critically evaluate the evidence showing that oxidative stress is an important
      factor in HD skin toxicity. Oxidative stress results when the production of
      reactive oxygen (ROS) and/or reactive nitrogen oxide species (RNOS) exceeds the
      capacity of antioxidant defense mechanisms. METHODS: This review will discuss the
      role of oxidative stress in the pathophysiology of HD skin toxicity in both in
      vivo and in vitro model systems with emphasis on the limitations of the various
      model systems. Evidence supporting the therapeutic potential of antioxidants and
      antioxidant liposomes will be evaluated. Antioxidant liposomes are effective
      vehicles for delivering both lipophilic (incorporated into the lipid bilayers)
      and water-soluble (encapsulated in the aqueous inner-spaces) antioxidants to
      skin. The molecular mechanisms interconnecting oxidative stress to HD skin
      toxicity are also detailed. RESULTS: DNA repair and inflammation, in association
      with oxidative stress, induce intracellular events leading to apoptosis or to a
      programmable form of necrosis. The free radical, nitric oxide (NO), is of
      considerable interest with respect to the mechanisms of HD toxicity. NO signaling
      pathways are important in modulating inflammation, cell death, and wound healing
      in skin cells. CONCLUSIONS: Potential future directions are summarized with
      emphasis on a systems biology approach to studying sulfur mustard toxicity to
      skin as well as the newly emerging area of redox proteomics.

PMID- 18091985
TI  - The increasing problem of wound bacterial burden and infection in acute and
      chronic soft-tissue wounds caused by methicillin-resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has become a leading cause of
      colonization and infection in both acute and chronic soft-tissue wounds.
      OBJECTIVE: Our objective is to define this current epidemic problem caused by
      both community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA),
      focusing on the similarities and differences between these 2 isolates as well as
      the impact on wound management decisions. METHODS: Methods used include a
      literature review on the growth of the current MRSA problem and its International
      scope. In addition, a current up-to-date assessment had been made of the problem
      and the current approach to management of MRSA in acute soft-tissue and chronic
      wounds. Burns are not discussed because this injury usually does not fit either
      categories and is managed quite uniquely. RESULTS: Results included the
      following: (1) There are very distinct properties of CA-MRSA and HA-MRSA, which
      must be considered for acute and chronic wound care. Management of both requires
      rigorous barrier precaution techniques to avoid cross-contamination. The presence
      of MRSA as a carrier state increases the risk of both a systemic and local wound
      infection in the carrier. There are large and increasing reservoirs of CA-MRSA
      and HA-MRSA worldwide leading to more bacteremias and wound problems. Topical
      antimicrobial therapy has not been addressed in managing MRSA in acute and
      chronic wounds. CONCLUSION: Conclusions include the fact that both HA-MRSA and CA
      MRSA wound infections are rapidly increasing, especially with CA-MRSA. This high
      incidence requires appropriate wound prediction and management decisions as well
      as attempts to avoid further cross-contamination and reservoir growth. Topical
      antimicrobial therapy would seem to be an important component in controlling this
      tremendous problem. Yet this topic has yet to be adequately addressed.

PMID- 18091986
TI  - What are you feeling? Using functional magnetic resonance imaging to assess the
      modulation of sensory and affective responses during empathy for pain.
AB  - BACKGROUND: Recent neuroscientific evidence suggests that empathy for pain
      activates similar neural representations as the first-hand experience of pain.
      However, empathy is not an all-or-none phenomenon but it is strongly malleable by
      interpersonal, intrapersonal and situational factors. This study investigated how
      two different top-down mechanisms - attention and cognitive appraisal - affect
      the perception of pain in others and its neural underpinnings.
      METHODOLOGY/PRINCIPAL FINDINGS: We performed one behavioral (N = 23) and two
      functional magnetic resonance imaging (fMRI) experiments (N = 18). In the first
      fMRI experiment, participants watched photographs displaying painful needle
      injections, and were asked to evaluate either the sensory or the affective
      consequences of these injections. The role of cognitive appraisal was examined in
      a second fMRI experiment in which participants watched injections that only
      appeared to be painful as they were performed on an anesthetized hand. Perceiving
      pain in others activated the affective-motivational and sensory-discriminative
      aspects of the pain matrix. Activity in the somatosensory areas was specifically
      enhanced when participants evaluated the sensory consequences of pain. Perceiving
      non-painful injections into the anesthetized hand also led to signal increase in
      large parts of the pain matrix, suggesting an automatic affective response to the
      putatively harmful stimulus. This automatic response was modulated by areas
      involved in self/other distinction and valence attribution - including the
      temporo-parietal junction and medial orbitofrontal cortex.
      CONCLUSIONS/SIGNIFICANCE: Our findings elucidate how top-down control mechanisms
      and automatic bottom-up processes interact to generate and modulate other
      oriented responses. They stress the role of cognitive processing in empathy, and
      shed light on how emotional and bodily awareness enable us to evaluate the
      sensory and affective states of others.

PMID- 18091987
TI  - SAVVY (C31G) gel for prevention of HIV infection in women: a Phase 3, double
      blind, randomized, placebo-controlled trial in Ghana.
AB  - OBJECTIVE: The objective of this trial was to determine the effectiveness of 1.0%
      C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection
      among women at high risk. METHODOLOGY/PRINCIPAL FINDINGS: This was a Phase 3,
      double-blind, randomized, placebo-controlled trial. Participants made up to 12
      monthly visits for HIV testing, adverse event reporting, and study product
      supply. The study was conducted between March 2004 and February 2006 in Accra and
      Kumasi, Ghana. We enrolled 2142 HIV-negative women at high risk of HIV infection,
      and randomized them to SAVVY or placebo gel. Main outcome measures were the
      incidence of HIV-1 and HIV-2 infection as determined by detection of HIV
      antibodies from oral mucosal transudate specimens and adverse events. We accrued
      790 person-years of follow-up in the SAVVY group and 772 person-years in the
      placebo group. No clinically significant differences in the overall frequency of
      adverse events, abnormal pelvic examination findings, or abnormal laboratory
      results were seen between treatment groups. However, more participants in the
      SAVVY group reported reproductive tract adverse events than in the placebo group
      (13.0% versus 9.4%). Seventeen HIV seroconversions occurred; eight in
      participants randomized to SAVVY and nine in participants receiving placebo. The
      Kaplan-Meier estimates of the cumulative probability of HIV infection through 12
      months were 0.010 in the SAVVY group and 0.011 in the placebo group (p = 0.731),
      with a hazard ratio (SAVVY versus placebo) of 0.88 (95% confidence interval 0.33,
      2.27). Because of a lower-than-expected HIV incidence, we were unable to achieve
      the required number of HIV infections (66) to obtain the desired study power.
      CONCLUSIONS/SIGNIFICANCE: SAVVY was not associated with increased adverse events
      overall, but was associated with higher reporting of reproductive adverse events.
      Our data are insufficient to conclude whether SAVVY is effective at preventing
      HIV infection relative to placebo. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00129532.

PMID- 18091988
TI  - Identification of novel high-frequency DNA methylation changes in breast cancer.
AB  - Recent data have revealed that epigenetic alterations, including DNA methylation
      and chromatin structure changes, are among the earliest molecular abnormalities
      to occur during tumorigenesis. The inherent thermodynamic stability of cytosine
      methylation and the apparent high specificity of the alterations for disease may
      accelerate the development of powerful molecular diagnostics for cancer. We
      report a genome-wide analysis of DNA methylation alterations in breast cancer.
      The approach efficiently identified a large collection of novel differentially
      DNA methylated loci (approximately 200), a subset of which was independently
      validated across a panel of over 230 clinical samples. The differential cytosine
      methylation events were independent of patient age, tumor stage, estrogen
      receptor status or family history of breast cancer. The power of the global
      approach for discovery is underscored by the identification of a single
      differentially methylated locus, associated with the GHSR gene, capable of
      distinguishing infiltrating ductal breast carcinoma from normal and benign breast
      tissues with a sensitivity and specificity of 90% and 96%, respectively. Notably,
      the frequency of these molecular abnormalities in breast tumors substantially
      exceeds the frequency of any other single genetic or epigenetic change reported
      to date. The discovery of over 50 novel DNA methylation-based biomarkers of
      breast cancer may provide new routes for development of DNA methylation-based
      diagnostics and prognostics, as well as reveal epigenetically regulated mechanism
      involved in breast tumorigenesis.

PMID- 18091989
TI  - A new in vitro strand transfer assay for monitoring bacterial class 1 integron
      recombinase IntI1 activity.
AB  - IntI1 integrase is a tyrosine recombinase involved in the mobility of antibiotic
      resistance gene cassettes within bacterial class 1 integrons. Recent data have
      shown that its recombination specifically involves the bottom strand of the attC
      site, but the exact mechanism of the reaction is still unclear. An efficient in
      vitro assay is still required to better characterize the biochemical properties
      of the enzyme. In this report we describe for the first time an in vitro system
      partially reproducing the activity of a recombinant pure IntI1. This new assay,
      which constitutes the only available in vitro model of recombination by IntI1,
      was used to determine whether this enzyme might be the sole bacterial protein
      required for the recombination process. Results show that IntI1 possesses all the
      features needed for performing recombination between attI and attC sites.
      However, differences in the in vitro intermolecular recombination efficiencies
      were found according to the target sites and were correlated with DNA affinities
      of the enzyme but not with in vivo data. The differential affinity of the enzyme
      for each site, its capacity to bind to a single-stranded structure at the attC
      site and the recombination observed with single-stranded substrates unambiguously
      confirm that it constitutes an important intermediary in the reaction. Our data
      strongly suggest that the enzyme possesses all the functions for generating
      and/or recognizing this structure even in the absence of other cellular factors.
      Furthermore, the in vitro assay reported here constitutes a powerful tool for the
      analysis of the recombination steps catalyzed by IntI1, its structure-function
      studies and the search for specific inhibitors.

PMID- 18091990
TI  - Candida albicans modulates host defense by biosynthesizing the pro-resolving
      mediator resolvin E1.
AB  - Candida albicans is an opportunistic fungal pathogen of humans that resides
      commensally on epithelial surfaces, but can cause inflammation when pathogenic.
      Resolvins are a class of anti-inflammatory lipids derived from omega-3
      polyunsaturated fatty acids (PUFA) that attenuate neutrophil migration during the
      resolution phase of inflammation. In this report we demonstrate that C. albicans
      biosynthesizes resolvins that are chemically identical to those produced by human
      cells. In contrast to the trans-cellular biosynthesis of human Resolvin E1
      (RvE1), RvE1 biosynthesis in C. albicans occurs in the absence of other cellular
      partners. C. albicans biosynthesis of RvE1 is sensitive to lipoxygenase and
      cytochrome P450 monoxygenase inhibitors. We show that 10nM RvE1 reduces
      neutrophil chemotaxis in response to IL-8; 1nM RvE1 enhanced phagocytosis of
      Candida by human neutrophils, as well as intracellular ROS generation and
      killing, while having no direct affect on neutrophil motility. In a mouse model
      of systemic candidiasis, RvE1 stimulated clearance of the fungus from circulating
      blood. These results reveal an inter-species chemical signaling system that
      modulates host immune functions and may play a role in balancing host carriage of
      commensal and pathogenic C. albicans.

PMID- 18091991
TI  - Full-exon resequencing reveals toll-like receptor variants contribute to human
      susceptibility to tuberculosis disease.
AB  - Tuberculosis (TB) is the leading cause of death worldwide due to an infectious
      agent. Data have accumulated over decades suggesting that variability in human
      susceptibility to TB disease has a genetic component. Toll-like receptors (TLRs)
      play a critical role in initiating the innate immune response to many pathogens
      in mouse models, but little is known about their role in human infections. Human
      TLRs have been reported to recognize mycobacterial antigens and initiate an
      immune response. We tested the hypothesis that amino acid-altering polymorphisms
      in five TLRs were associated with susceptibility to TB disease using a population
      based case-control study with 1,312 adult TB patients and controls. Full-coding
      region sequencing of the five TLR genes in all 1,312 subjects yielded a data set
      in excess of 16 Mb. Rare nonsynonymous polymorphisms in TLR6-TLR1-TLR10 were
      significantly overrepresented among African-American TB cases compared with
      ethnically-matched control subjects. Common nonsynonymous polymorphisms in TLR6
      TLR1-TLR10 also were significantly associated with TB disease in certain ethnic
      groups. Among African Americans, homozygotes for the common-variant haplotype
      TLR1-248S, TLR1-602I, and TLR6-249S had a significantly increased TB disease
      risk. A transmission/disequilibrium test on an independent sample found that the
      TLR1-248S variant was preferentially transmitted to diseased children, thereby
      confirming disease association. These results are consistent with recent reports
      implicating TLR1 variants, including TLR1-602, in significantly altered innate
      immune responses. Also consistent with disease association, rare TLR6 variants
      were defective in their ability to mediate NF-kappaB signal transduction in
      transfected human cells. Taken together, the data suggest that variant TLRs
      contribute to human susceptibility to TB disease. Extensive full-exon
      resequencing was critical for revealing new information about the role of TLRs in
      human-pathogen interactions and the genetic basis of innate immune function.

PMID- 18091992
TI  - A family of chemoreceptors in Tribolium castaneum (Tenebrionidae: Coleoptera).
AB  - Chemoperception in invertebrates is mediated by a family of G-protein-coupled
      receptors (GPCR). To date nothing is known about the molecular mechanisms of
      chemoperception in coleopteran species. Recently the genome of Tribolium
      castaneum was sequenced for use as a model species for the Coleoptera. Using
      blast searches analyses of the T. castaneum genome with previously predicted
      amino acid sequences of insect chemoreceptor genes, a putative chemoreceptor
      family consisting of 62 gustatory receptors (Grs) and 26 olfactory receptors
      (Ors) was identified. The receptors have seven transmembrane domains (7TMs) and
      all belong to the GPCR receptor family. The expression of the T. castaneum
      chemoreceptor genes was investigated using quantification real- time RT-PCR and
      in situ whole mount RT-PCR analysis in the antennae, mouth parts, and prolegs of
      the adults and larvae. All of the predicted TcasGrs were expressed in the labium,
      maxillae, and prolegs of the adults but TcasGr13, 19, 28, 47, 62, 98, and 61 were
      not expressed in the prolegs. The TcasOrs were localized only in the antennae and
      not in any of the beetles gustatory organs with one exception; the TcasOr16 (like
      DmelOr83b), which was localized in the antennae, labium, and prolegs of the
      beetles. A group of six TcasGrs that presents a lineage with the sugar receptors
      subfamily in Drosophila melanogaster were localized in the lacinia of the
      Tribolium larvae. TcasGr1, 3, and 39, presented an ortholog to CO(2) receptors in
      D. melanogaster and Anopheles gambiae was recorded. Low expression of almost all
      of the predicted chemoreceptor genes was observed in the head tissues that
      contain the brains and suboesophageal ganglion (SOG). These findings demonstrate
      the identification of a chemoreceptor family in Tribolium, which is
      evolutionarily related to other insect species.

PMID- 18091993
TI  - Alloxan-induced diabetes triggers the development of periodontal disease in rats.
AB  - BACKGROUND: Periodontal disease in diabetic patients presents higher severity and
      prevalence; and increased severity of ligature-induced periodontal disease has
      been verified in diabetic rats. However, in absence of aggressive stimuli such as
      ligatures, the influence of diabetes on rat periodontal tissues is incompletely
      explored. The aim of this study was to evaluate the establishment and progression
      of periodontal diseases in rats only with diabetes induction.
      METHODOLOGY/PRINCIPAL FINDINGS: Diabetes was induced in Wistar rats (n = 25) by
      intravenous administration of alloxan (42 mg/kg) and were analyzed at 1, 3, 6, 9
      and 12 months after diabetes induction. The hemimandibles were removed and
      submitted to radiographical and histopathological procedures. A significant
      reduction was observed in height of bone crest in diabetic animals at 3, 6, 9 and
      12 months, which was associated with increased numbers of osteoclasts and
      inflammatory cells. The histopathological analyses of diabetic rats also showed a
      reduction in density of collagen fibers, fibroblasts and blood vessels. Severe
      caries were also detected in the diabetic group. CONCLUSIONS/SIGNIFICANCE: The
      results demonstrate that diabetes induction triggers, or even co-induces the
      onset of alterations which are typical of periodontal diseases even in the
      absence of aggressive factors such as ligatures. Therefore, diabetes induction
      renders a previously resistant host into a susceptible phenotype, and hence
      diabetes can be considered a very important risk factor to the development of
      periodontal disease.

PMID- 18091994
TI  - Salvianolic acid B inhibits hydrogen peroxide-induced endothelial cell apoptosis
      through regulating PI3K/Akt signaling.
AB  - BACKGROUND: Salvianolic acid B (Sal B) is one of the most bioactive components of
      Salvia miltiorrhiza, a traditional Chinese herbal medicine that has been commonly
      used for prevention and treatment of cerebrovascular disorders. However, the
      mechanism responsible for such protective effects remains largely unknown. It has
      been considered that cerebral endothelium apoptosis caused by reactive oxygen
      species including hydrogen peroxide (H(2)O(2)) is implicated in the pathogenesis
      of cerebrovascular disorders. METHODOLOGY AND PRINCIPAL FINDINGS: By examining
      the effect of Sal B on H(2)O(2)-induced apoptosis in rat cerebral microvascular
      endothelial cells (rCMECs), we found that Sal B pretreatment significantly
      attenuated H(2)O(2)-induced apoptosis in rCMECs. We next examined the signaling
      cascade(s) involved in Sal B-mediated anti-apoptotic effects. We showed that
      H(2)O(2) induces rCMECs apoptosis mainly through the PI3K/ERK pathway, since a
      PI3K inhibitor (LY294002) blocked ERK activation caused by H(2)O(2 )and a
      specific inhibitor of MEK (U0126) protected cells from apoptosis. On the other
      hand, blockage of the PI3K/Akt pathway abrogated the protective effect conferred
      by Sal B and potentated H(2)O(2)-induced apoptosis, suggesting that Sal B
      prevents H(2)O(2)-induced apoptosis predominantly through the PI3K/Akt (upstream
      of ERK) pathway. SIGNIFICANCE: Our findings provide the first evidence that
      H(2)O(2) induces rCMECs apoptosis via the PI3K/MEK/ERK pathway and that Sal B
      protects rCMECs against H(2)O(2)-induced apoptosis through the
      PI3K/Akt/Raf/MEK/ERK pathway.

PMID- 18091995
TI  - Canine population structure: assessment and impact of intra-breed stratification
      on SNP-based association studies.
AB  - BACKGROUND: In canine genetics, the impact of population structure on whole
      genome association studies is typically addressed by sampling approximately equal
      numbers of cases and controls from dogs of a single breed, usually from the same
      country or geographic area. However one way to increase the power of genetic
      studies is to sample individuals of the same breed but from different geographic
      areas, with the expectation that independent meiotic events will have shortened
      the presumed ancestral haplotype around the mutation differently. Little is
      known, however, about genetic variation among dogs of the same breed collected
      from different geographic regions. METHODOLOGY/PRINCIPAL FINDINGS: In this
      report, we address the magnitude and impact of genetic diversity among common
      breeds sampled in the U.S. and Europe. The breeds selected, including the
      Rottweiler, Bernese mountain dog, flat-coated retriever, and golden retriever,
      share susceptibility to a class of soft tissue cancers typified by malignant
      histiocytosis in the Bernese mountain dog. We genotyped 722 SNPs at four unlinked
      loci (between 95 and 271 per locus) on canine chromosome 1 (CFA1). We showed that
      each population is characterized by distinct genetic diversity that can be
      correlated with breed history. When the breed studied has a reduced intra-breed
      diversity, the combination of dogs from international locations does not increase
      the rate of false positives and potentially increases the power of association
      studies. However, over-sampling cases from one geographic location is more likely
      to lead to false positive results in breeds with significant genetic diversity.
      CONCLUSIONS: These data provide new guidelines for association studies using
      purebred dogs that take into account population structure.

PMID- 18091996
TI  - Modification of hydrophilic and hydrophobic surfaces using an ionic-complementary
      peptide.
AB  - Ionic-complementary peptides are novel nano-biomaterials with a variety of
      biomedical applications including potential biosurface engineering. This study
      presents evidence that a model ionic-complementary peptide EAK16-II is capable of
      assembling/coating on hydrophilic mica as well as hydrophobic highly ordered
      pyrolytic graphite (HOPG) surfaces with different nano-patterns. EAK16-II forms
      randomly oriented nanofibers or nanofiber networks on mica, while ordered
      nanofibers parallel or oriented 60 degrees or 120 degrees to each other on HOPG,
      reflecting the crystallographic symmetry of graphite (0001). The density of
      coated nanofibers on both surfaces can be controlled by adjusting the peptide
      concentration and the contact time of the peptide solution with the surface. The
      coated EAK16-II nanofibers alter the wettability of the two surfaces differently:
      the water contact angle of bare mica surface is measured to be <10 degrees ,
      while it increases to 20.3+/-2.9 degrees upon 2 h modification of the surface
      using a 29 microM EAK16-II solution. In contrast, the water contact angle
      decreases significantly from 71.2+/-11.1 degrees to 39.4+/-4.3 degrees after the
      HOPG surface is coated with a 29 microM peptide solution for 2 h. The stability
      of the EAK16-II nanofibers on both surfaces is further evaluated by immersing the
      surface into acidic and basic solutions and analyzing the changes in the
      nanofiber surface coverage. The EAK16-II nanofibers on mica remain stable in
      acidic solution but not in alkaline solution, while they are stable on the HOPG
      surface regardless of the solution pH. This work demonstrates the possibility of
      using self-assembling peptides for surface modification applications.

PMID- 18091997
TI  - High-pass filtering of input signals by the Ih current in a non-spiking neuron,
      the retinal rod bipolar cell.
AB  - Hyperpolarization-activated cyclic nucleotide-sensitive (HCN) channels mediate
      the I(f) current in heart and I(h) throughout the nervous system. In spiking
      neurons I(h) participates primarily in different forms of rhythmic activity.
      Little is known, however, about its role in neurons operating with graded
      potentials as in the retina, where all four channel isoforms are expressed.
      Intriguing evidence for an involvement of I(h) in early visual processing are the
      side effects reported, in dim light or darkness, by cardiac patients treated with
      HCN inhibitors. Moreover, electroretinographic recordings indicate that these
      drugs affect temporal processing in the outer retina. Here we analyzed the
      functional role of HCN channels in rod bipolar cells (RBCs) of the mouse.
      Perforated-patch recordings in the dark-adapted slice found that RBCs exhibit
      I(h), and that this is sensitive to the specific blocker ZD7288. RBC input
      impedance, explored by sinusoidal frequency-modulated current stimuli (0.1-30
      Hz), displays band-pass behavior in the range of I(h) activation. Theoretical
      modeling and pharmacological blockade demonstrate that high-pass filtering of
      input signals by I(h), in combination with low-pass filtering by passive
      properties, fully accounts for this frequency-tuning. Correcting for the
      depolarization introduced by shunting through the pipette-membrane seal, leads to
      predict that in darkness I(h) is tonically active in RBCs and quickens their
      responses to dim light stimuli. Immunohistochemistry targeting candidate subunit
      isoforms HCN1-2, in combination with markers of RBCs (PKC) and rod-RBC synaptic
      contacts (bassoon, mGluR6, Kv1.3), suggests that RBCs express HCN2 on the tip of
      their dendrites. The functional properties conferred by I(h) onto RBCs may
      contribute to shape the retina's light response and explain the visual side
      effects of HCN inhibitors.

PMID- 18091998
TI  - Information and discriminability as measures of reliability of sensory coding.
AB  - Response variability is a fundamental issue in neural coding because it limits
      all information processing. The reliability of neuronal coding is quantified by
      various approaches in different studies. In most cases it is largely unclear to
      what extent the conclusions depend on the applied reliability measure, making a
      comparison across studies almost impossible. We demonstrate that different
      reliability measures can lead to very different conclusions even if applied to
      the same set of data: in particular, we applied information theoretical measures
      (Shannon information capacity and Kullback-Leibler divergence) as well as a
      discrimination measure derived from signal-detection theory to the responses of
      blowfly photoreceptors which represent a well established model system for
      sensory information processing. We stimulated the photoreceptors with white noise
      modulated light intensity fluctuations of different contrasts. Surprisingly, the
      signal-detection approach leads to a safe discrimination of the photoreceptor
      response even when the response signal-to-noise ratio (SNR) is well below unity
      whereas Shannon information capacity and also Kullback-Leibler divergence
      indicate a very low performance. Applying different measures, can, therefore,
      lead to very different interpretations concerning the system's coding
      performance. As a consequence of the lower sensitivity compared to the signal
      detection approach, the information theoretical measures overestimate internal
      noise sources and underestimate the importance of photon shot noise. We stress
      that none of the used measures and, most likely no other measure alone, allows
      for an unbiased estimation of a neuron's coding properties. Therefore the applied
      measure needs to be selected with respect to the scientific question and the
      analyzed neuron's functional context.

PMID- 18091999
TI  - Serotonin differentially regulates short- and long-term prediction of rewards in
      the ventral and dorsal striatum.
AB  - BACKGROUND: The ability to select an action by considering both delays and amount
      of reward outcome is critical for maximizing long-term benefits. Although
      previous animal experiments on impulsivity have suggested a role of serotonin in
      behaviors requiring prediction of delayed rewards, the underlying neural
      mechanism is unclear. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the role of
      serotonin in the evaluation of delayed rewards, we performed a functional brain
      imaging experiment in which subjects chose small-immediate or large-delayed
      liquid rewards under dietary regulation of tryptophan, a precursor of serotonin.
      A model-based analysis revealed that the activity of the ventral part of the
      striatum was correlated with reward prediction at shorter time scales, and this
      correlated activity was stronger at low serotonin levels. By contrast, the
      activity of the dorsal part of the striatum was correlated with reward prediction
      at longer time scales, and this correlated activity was stronger at high
      serotonin levels. CONCLUSIONS/SIGNIFICANCE: Our results suggest that serotonin
      controls the time scale of reward prediction by differentially regulating
      activities within the striatum.

PMID- 18092000
TI  - The Cebpd (C/EBPdelta) gene is induced by luteinizing hormones in ovarian theca
      and interstitial cells but is not essential for mouse ovary function.
AB  - The CCAAT/enhancer binding protein (CEBP) family of transcription factors
      includes five genes. In the ovary, both Cebpa and Cebpb are essential for
      granulosa cell function. In this study we have explored the role of the Cebpd
      gene in ovarian physiology by expression and functional studies. Here we report
      that Cebpd (C/EBPdelta) is expressed in the mouse ovary in a highly restricted
      temporal and spatial pattern. In response to luteinizing hormone (LH/hCG), CEBPD
      expression is transiently induced in interstitial cells and in theca cells of
      follicles from the primary to pre-ovulatory stage, and overlaps in part with
      expression of the alpha-smooth muscle actin protein. Efficient down-regulation of
      CEBPD was dependent on a functional Cebpb gene. Proliferating human theca cells
      in culture also express Cebpd. Cells from patients with polycystic ovarian
      syndrome (PCOS) exhibited higher Cebpd expression levels. However, deletion of
      Cebpd in mice had no overt effect on ovarian physiology and reproductive
      function. Very little is known at present about the molecular mechanisms
      underlying theca/interstitial cell functions. The expression pattern of CEBPD
      reported here identifies a novel functional unit of mouse theca cells of primary
      through tertiary follicles responding to LH/hCG together with a subset of
      interstitial cells. This acute stimulation of CEBPD expression may be exploited
      to further characterize the hormonal regulation and function of theca and
      interstitial cells.

PMID- 18092001
TI  - Rapid diagnosis of smear-negative tuberculosis using immunology and microbiology
      with induced sputum in HIV-infected and uninfected individuals.
AB  - RATIONALE AND OBJECTIVES: Blood-based studies have demonstrated the potential of
      immunological assays to detect tuberculosis. However lung fluid sampling may
      prove superior as it enables simultaneous microbiological detection of
      mycobacteria to be performed. Until now this has only been possible using the
      expensive and invasive technique of broncho-alveolar lavage. We sought to
      evaluate an immunoassay using non-invasive induced-sputum to diagnose active
      tuberculosis. METHODS AND RESULTS: Prospective cohort study of forty-two
      spontaneous sputum smear-negative or sputum non-producing adults under
      investigation for tuberculosis. CD4 lymphocytes specific to purified-protein
      derivative of Mycobacterium tuberculosis actively synthesising interferon-gamma
      were measured by flow cytometry and final diagnosis compared to immunoassay using
      a cut-off of 0.5%. Sixteen subjects (38%) were HIV-infected (median CD4 count
      [range] = 332 cells/microl [103-748]). Thirty-eight (90%) were BCG-vaccinated. In
      27 subjects diagnosed with active tuberculosis, the median [range] percentage of
      interferon-gamma synthetic CD4+ lymphocytes was 2.77% [0-23.93%] versus 0% [0
      2.10%] in 15 negative for active infection (p<0.0001). Sensitivity and
      specificity of the immunoassay versus final diagnosis of active tuberculosis were
      89% (24 of 27) and 80% (12 of 15) respectively. The 3 positive assays in the
      latter group occurred in subjects diagnosed with quiescent/latent tuberculosis.
      Assay performance was unaffected by HIV-status, BCG-vaccination or disease site.
      Combining this approach with traditional microbiological methods increased the
      diagnostic yield to 93% (25 of 27) alongside acid-fast bacilli smear and 96% (26
      of 27) alongside tuberculosis culture. CONCLUSIONS: These data demonstrate for
      the first time that a rapid immunological assay to diagnose active tuberculosis
      can be performed successfully in combination with microbiological methods on a
      single induced-sputum sample.

PMID- 18092002
TI  - Visual feedback is not necessary for the learning of novel dynamics.
AB  - BACKGROUND: When learning to perform a novel sensorimotor task, humans integrate
      multi-modal sensory feedback such as vision and proprioception in order to make
      the appropriate adjustments to successfully complete the task. Sensory feedback
      is used both during movement to control and correct the current movement, and to
      update the feed-forward motor command for subsequent movements. Previous work has
      shown that adaptation to stable dynamics is possible without visual feedback.
      However, it is not clear to what degree visual information during movement
      contributes to this learning or whether it is essential to the development of an
      internal model or impedance controller. METHODOLOGY/PRINCIPLE FINDINGS: We
      examined the effects of the removal of visual feedback during movement on the
      learning of both stable and unstable dynamics in comparison with the case when
      both vision and proprioception are available. Subjects were able to learn to make
      smooth movements in both types of novel dynamics after learning with or without
      visual feedback. By examining the endpoint stiffness and force after learning it
      could be shown that subjects adapted to both types of dynamics in the same way
      whether they were provided with visual feedback of their trajectory or not. The
      main effects of visual feedback were to increase the success rate of movements,
      slightly straighten the path, and significantly reduce variability near the end
      of the movement. CONCLUSIONS/SIGNIFICANCE: These findings suggest that visual
      feedback of the hand during movement is not necessary for the adaptation to
      either stable or unstable novel dynamics. Instead vision appears to be used to
      fine-tune corrections of hand trajectory at the end of reaching movements.

PMID- 18092003
TI  - Id1 restrains p21 expression to control endothelial progenitor cell formation.
AB  - Loss of Id1 in the bone marrow (BM) severely impairs tumor angiogenesis resulting
      in significant inhibition of tumor growth. This phenotype has been associated
      with the absence of circulating endothelial progenitor cells (EPCs) in the
      peripheral blood of Id1 mutant mice. However, the manner in which Id1 loss in the
      BM controls EPC generation or mobilization is largely unknown. Using genetically
      modified mouse models we demonstrate here that the generation of EPCs in the BM
      depends on the ability of Id1 to restrain the expression of its target gene p21.
      Through a series of cellular and functional studies we show that the increased
      myeloid commitment of BM stem cells and the absence of EPCs in Id1 knockout mice
      are associated with elevated p21 expression. Genetic ablation of p21 rescues the
      EPC population in the Id1 null animals, re-establishing functional BM-derived
      angiogenesis and restoring normal tumor growth. These results demonstrate that
      the restraint of p21 expression by Id1 is one key element of its activity in
      facilitating the generation of EPCs in the BM and highlight the critical role
      these cells play in tumor angiogenesis.

PMID- 18092004
TI  - Expression analysis of the ligands for the Natural Killer cell receptors NKp30
      and NKp44.
AB  - BACKGROUND: The natural cytotoxicity receptors (NCR) are important to stimulate
      the activity of Natural Killer (NK) cells against transformed cells.
      Identification of NCR ligands and their level of expression on normal and
      neoplastic cells has important implications for the rational design of
      immunotherapy strategies for cancer. METHODOLOGY/PRINCIPAL FINDINGS: Here we
      analyze the expression of NKp30 ligand and NKp44 ligand on 30 transformed or non
      transformed cell lines of different origin. We find intracellular and surface
      expression of these two ligands on almost all cell lines tested. Expression of
      NKp30 and NKp44 ligands was variable and did not correlate with the origin of the
      cell line. Expression of NKp30 and NKp44 ligand correlated with NKp30 and NKp44
      mediated NK cell lysis of tumor cells, respectively. The surface expression of
      NKp30 ligand and NKp44 ligand was sensitive to trypsin treatment and was reduced
      in cells arrested in G(2)/M phase. CONCLUSION/SIGNIFICANCE: These data
      demonstrate the ubiquitous expression of the ligands for NKp30 and NKp44 and give
      an important insight into the regulation of these ligands.

PMID- 18092006
TI  - Light variability illuminates niche-partitioning among marine Picocyanobacteria.
AB  - Prochlorococcus and Synechococcus picocyanobacteria are dominant contributors to
      marine primary production over large areas of the ocean. Phytoplankton cells are
      entrained in the water column and are thus often exposed to rapid changes in
      irradiance within the upper mixed layer of the ocean. An upward fluctuation in
      irradiance can result in photosystem II photoinactivation exceeding counteracting
      repair rates through protein turnover, thereby leading to net photoinhibition of
      primary productivity, and potentially cell death. Here we show that the effective
      cross-section for photosystem II photoinactivation is conserved across the
      picocyanobacteria, but that their photosystem II repair capacity and protein
      specific photosystem II light capture are negatively correlated and vary widely
      across the strains. The differences in repair rate correspond to the light and
      nutrient conditions that characterize the site of origin of the Prochlorococcus
      and Synechococcus isolates, and determine the upward fluctuation in irradiance
      they can tolerate, indicating that photoinhibition due to transient high-light
      exposure influences their distribution in the ocean.

PMID- 18092005
TI  - Role of PSIP1/LEDGF/p75 in lentiviral infectivity and integration targeting.
AB  - BACKGROUND: To replicate, lentiviruses such as HIV must integrate DNA copies of
      their RNA genomes into host cell chromosomes. Lentiviral integration is favored
      in active transcription units, which allows efficient viral gene expression after
      integration, but the mechanisms directing integration targeting are incompletely
      understood. A cellular protein, PSIP1/LEDGF/p75, binds tightly to the lentiviral
      encoded integrase protein (IN), and has been reported to be important for HIV
      infectivity and integration targeting. METHODOLOGY: Here we report studies of
      lentiviral integration targeting in 1) human cells with intensified RNAi
      knockdowns of PSIP1/LEDGF/p75, and 2) murine cells with homozygous gene trap
      mutations in the PSIP1/LEDGF/p75 locus. Infections with vectors derived from
      equine infections anemia virus (EIAV) and HIV were compared. Integration acceptor
      sites were analyzed by DNA bar coding and pyrosequencing.
      CONCLUSIONS/SIGNIFICANCE: In both PSIP1/LEDGF/p75-depleted cell lines, reductions
      were seen in lentiviral infectivity compared to controls. For the human cells,
      integration was reduced in transcription units in the knockdowns, and this
      reduction was greater than in our previous studies of human cells less completely
      depleted for PSIP1/LEDGF/p75. For the homozygous mutant mouse cells, similar
      reductions in integration in transcription units were seen, paralleling a
      previous study of a different mutant mouse line. Integration did not become
      random, however-integration in transcription units in both cell types was still
      favored, though to a reduced degree. New trends also appeared, including favored
      integration near CpG islands. In addition, we carried out a bioinformatic study
      of 15 HIV integration site data sets in different cell types, which showed that
      the frequency of integration in transcription units was correlated with the cell
      type specific levels of PSIP1/LEDGF/p75 expression.

PMID- 18092008
TI  - To be a great physician, you must understand the whole story.

PMID- 18092007
TI  - Neural induction from ES cells portrays default commitment but instructive
      maturation.
AB  - The neural induction has remained a debatable issue pertaining to whether it is a
      mere default process or it involves precise instructive cues. We have chosen the
      embryonic stem (ES) cell model to address this issue. In a devised monoculture
      strategy, the cell-cell interaction availed through optimum cell plating density
      could define the niche for the attainment of efficient in vitro neurogenesis from
      the ES cells. The medium plating density was found ideal in generating optimum
      number of progenitors and also yielded about 80% mature neurons in a serum free
      culture set up barring any exogenous inducers. We could also demarcate and
      quantify the neural stem cells/progenitors among the heterogeneous cell
      population of differentiating ES cells using nestin intron II driven EGFP
      expression as a tool. The one week post-plating was determined to be the critical
      time window for optimum neural progenitor generation from ES cells that helped us
      further in purifying these cells and in demonstrating their proliferation and
      multipotent differentiation potential. Seeding cells at varying densities, we
      could decipher an interesting paradoxical scenario that interlinked both
      commitment and maturation with the initial plating density having a vital
      influence on neuronal maturation but not specification and the secretory factors
      were apparently playing a key role during this process. Thus it was comprehended
      that, the neural specification was a default process independent of exogenous
      factors and cellular interaction. Conversely, a defined number of cells at the
      specification stage itself seemed critical to provide an auto-/paracrine means of
      signaling threshold for the maturation process to materialize.

PMID- 18092010
TI  - Tissue inhibitor of matrix metalloproteinase-2 in nasopharyngeal carcinoma.
AB  - By regulating matrix metalloproteinase (MMP) activity and controlling the
      breakdown of extracellular matrix components, tissue inhibitors of
      metalloproteinases (TIMPs) play an important role in the process of tumor
      invasion and metastasis. The present study was designed to clarify the role of
      TIMP-2 in nasopharyngeal carcinoma (NPC) patients and to evaluate its importance
      relative to clinicopathologic parameters. It was carried out in 30 patients with
      NPC and 20 controls. Tissue biopsies were studied and graded pathologically, and
      Western blot analysis was performed to assess TIMP-2 protein expression.
      Clinically, in accordance with TNM classification (T: tumor size, N: lymph node
      involvement, M: distant metastasis), 8 cases were diagnosed as stage II, 12 as
      stage III, and 10 cases as stage IV; however, pathologic typing with use of the
      World Health Organization (WHO) classification revealed the presence of 9
      specimens of squamous cell carcinoma (WHO type 1), 6 cases of nonkeratinizing
      carcinoma (WHO type 2), and 15 cases of undifferentiated carcinoma (WHO type 3).
      The difference in percentage of TIMP-2 positivity between NPC patients (76.6%)
      and normal controls (30%) was statistically highly significant (P < .01). In
      addition, there was a significant positive correlation between TIMP-2 protein
      positivity and either the clinical staging or the histopathologic typing (P <
      .01) using Chi-square test (x(2)), suggesting that TIMP-2 can be used as a marker
      of the severity of NPC.Accordingly, we can assume that TIMP-2 may play a role in
      regional lymph node and/or distant metastasis and in progression of squamous cell
      carcinoma. Further studies are needed to investigate the role of TIMP-2 as a
      marker for tumor progression and to evaluate its potential value in the follow-up
      of patients.

PMID- 18092012
TI  - A 'secret weapon' for reducing drug errors".

PMID- 18092014
TI  - I am not like your father's pharmacist.

PMID- 18092011
TI  - Acinetobacter pneumonia: a review.
AB  - Acinetobacter species are becoming a major cause of nosocomial infections,
      including hospital-acquired and ventilator-associated pneumonia. Acinetobacter
      species have become increasingly resistant to antibiotics over the past several
      years and currently present a significant challenge in treating these infections.
      Physicians now rely on older agents, such as polymyxins (colistin), for
      treatment. This paper reviews the epidemiology, treatment, and prevention of this
      emerging pathogen.

PMID- 18092015
TI  - Divergence in popular diets relative to diets consumed by Americans, and
      implications for diet selection.
AB  - CONTEXT: Given the seemingly disparate nature of popular weight-loss diets
      (WLDs), consumers may have a difficult time choosing one. We hypothesized that
      because most of these diets differ greatly from the way most Americans
      spontaneously eat, the choice of a WLD may be less critical than the decision to
      adopt any WLD. OBJECTIVE: To assess the degree of similarity among several
      popular WLDs and that between average diets of Americans and the WLDs as a whole.
      DESIGN: One-day menus were randomly selected or constructed from 16 popular diet
      books (resulting in 17 distinct diets). Usual dietary intakes of individuals were
      derived from the Continuing Survey of Food Intakes by Individuals (CSFII) 1994
      96, 1998. MAIN OUTCOME MEASURES: Euclidean distances, based on 12 dietary
      variables, were calculated among the popular WLDs, as well as between the WLDs
      and intakes from the CSFII. RESULTS: Euclidean distances among the WLDs ranged
      from 1.99 to 15.24, with a mean of 6.12 +/- 2.83. Mean distance between
      individuals' intakes from the CSFII and the closest WLD was 3.63 +/- 1.24, while
      the mean distance between individuals' intakes and the farthest WLD was 10.58 +/-
      1.10. Mean distance between individuals' intakes and the WLDs considered together
      was 6.04 +/- 1.10. CONCLUSIONS: While the mean Euclidean distances between
      individuals' intakes and popular WLDs demonstrated meaningful differences, the
      differences among the WLDs were slightly greater and, in multivariate space,
      surrounded the diets consumed by Americans. This may have implications for the
      selection of a WLD in persons seeking to lose weight.

PMID- 18092017
TI  - Base hospital 43: the Emory unit.

PMID- 18092018
TI  - The prevalence of anemia among pregnant women at booking in Enugu, South Eastern
      Nigeria.
AB  - BACKGROUND: More than half of the pregnant women in the world have hemoglobin
      levels indicative of anemia. Knowledge of the current situation of the condition
      in our environment is necessary. This knowledge will motivate antenatal
      caregivers toward early detection and prompt management of anemia in pregnancy.
      AIMS: Our aim was to determine the prevalence of anemia among pregnant women at
      registration for antenatal care at a major tertiary healthcare center in Enugu,
      southeastern Nigeria. METHODS: This was a retrospective study of 530 normal
      pregnant women registered with the antenatal unit of the University of Nigeria
      Teaching Hospital (UNTH), Enugu, between January 1, 2005 and October 30, 2005.
      Data on the age, parity, gestational age at booking, interval between last
      confinement and last menstrual period in the index pregnancy, hemoglobin
      concentration at booking, and HIV status were obtained and analyzed. RESULTS: The
      mean gestational age at booking was 21.7 +/- 7.1 weeks (range, 6-37). Two hundred
      fourteen (40.4%) of the women were anemic (hemoglobin [Hb] < 11.0 g/dL). The
      majority (90.7%) of these anemic patients were mildly anemic, whereas 9.3% were
      moderately anemic. There was no case of severe anemia (Hb < 7.0 g/dL). The
      prevalence of anemia at booking was significantly higher in those who registered
      for antenatal care in the third trimester than in those who registered in the
      second trimester, and in HIV-positive pregnant women than in HIV-negative ones (P
      = .00). The patients' age, parity, and the interval between the last confinement
      and the index pregnancy had no significant relationship with the hemoglobin
      concentration of pregnant women at booking (P > .05). CONCLUSION: The prevalence
      of anemia in pregnancy at booking is still high in Enugu. Preconception care,
      including iron and folic acid supplementation, is advocated to reduce this
      problem. Early antenatal booking and improved antenatal care are also necessary
      for early diagnosis and treatment of the condition. All would ensure safe
      motherhood.

PMID- 18092022
TI  - Case 17: sudden paralysis in a boy with headaches.

PMID- 18092023
TI  - Do medical journals provide clear and consistent guidelines on authorship?
AB  - CONTEXT: Determining the authorship of scientific papers can be difficult and
      authorship disputes are common. Less experienced authors may benefit from clear
      advice about authorship from journals while both authors and readers would
      benefit from consistent policies between journals. However, previous surveys of
      authors have suggested that there are no universally known or accepted criteria
      for determining authorship. OBJECTIVE: To review instructions to contributors
      from a broad sample of biomedical journals to discover how much guidance they
      provide about authorship and whether their advice is consistent with one another
      and with international guidelines. DESIGN: Review and analysis of published
      instructions to authors. SETTING: Biomedical journals that publish instructions
      in English on the Internet. METHODS: I examined the instructions to contributors
      from 234 biomedical journals (randomly selected from the membership list of the
      World Association of Medical Editors and from Medline). RESULTS: Of the 234
      instructions examined, 100 (41%) gave no guidance about authorship, 68 (29%) were
      based on the International Committee of Medical Journal Editors' (ICMJE)
      criteria, 33 (14%) proposed other criteria, and 33 (14%) said nothing except that
      all authors should have approved the manuscript. Of those instructions that were
      based on the ICMJE criteria, 18/51 (35%) cited an outdated version. Only 21 of
      the journals (9%) required individuals' contributions to be described.
      CONCLUSIONS: Journals do not provide consistent guidance about authorship and
      many editors are therefore missing an important opportunity to educate potential
      contributors and to improve the accuracy, fairness, and transparency of author
      listing.

PMID- 18092026
TI  - Muscular metastasis, a rare presentation of non-small-cell lung cancer.
AB  - A 71-year-old man presented with a 2-week history of pain and swelling of his
      left arm. Subsequent investigations revealed an intramuscular lesion, suggestive
      of soft tissue sarcoma. Histologic analysis was surprisingly consistent with
      metastasis from a primary squamous cell lung cancer. Skeletal muscle metastasis
      as a mode of presentation of primary lung cancer is an unusual phenomenon. A
      brief literature review accompanies this report.

PMID- 18092027
TI  - Use of depleted uranium is a form of radiologic warfare.

PMID- 18092030
TI  - Enhancing COPD management in primary care settings.
AB  - CONTEXT: Primary care physicians provide care for the majority of patients with
      mild-to-moderate chronic obstructive pulmonary disease (COPD). Although clinical
      practice guidelines have been developed for COPD, their influence on primary care
      practice is unclear. OBJECTIVE: To examine primary care decision making,
      perceptions, and educational needs relating to COPD. DESIGN: A survey centered on
      COPD case-vignettes was developed and distributed to a random sample of
      physicians in adult primary care specialties. RESULTS: From 943 respondents, 784
      practicing primary care physicians were used in analysis. On average, physicians
      estimated that 12% of their patients had COPD. Although 55% of physicians were
      aware of major COPD guidelines, only 25% used them to guide decision-making. Self
      identified guidelines showed that users were more likely to order spirometry for
      subtle respiratory symptoms (74% vs 63%, P < .01), to initiate therapy for mild
      symptoms (86% vs. 77%, P < .01), and to choose long-acting bronchodilators for
      persistent dyspnea (50% vs 32%, P < .01). CONCLUSIONS: Practice guidelines and
      CME programs are both valued resources, but have not yet adequately reached many
      physicians. Because guidelines appear to influence clinical decision-making,
      efforts to disseminate them more broadly are needed. Future education should
      present COPD assessment algorithms tailored to primary care settings, assess and
      strengthen spirometry interpretation skills, and discuss a reasoned approach to
      medication management. Patient-centered content that accurately reflects the
      nature of primary care practice may enhance physician's learning experience.
      Internet-based and distance learning formats may be essential for reaching
      physicians in many high-need areas.

PMID- 18092031
TI  - Secondary aortoenteric fistula.
AB  - Secondary aortoenteric fistula (SAF) is an uncommon but very important
      complication of abdominal aortic reconstruction. The complication often occurs
      months to years after aortic surgery. The clinical manifestation of the
      aortoenteric fistula is always upper gastrointestinal bleeding. Treatment of the
      disease is early surgical intervention. If operative treatment is not performed
      promptly, the mortality is high. A case of secondary aortoduodenal fistula found
      6 years after aortic reconstructive surgery, with the clinical presentation of
      upper gastrointestinal bleeding, is presented. On Immediate exploratory
      laparotomy, the proximal part of abdominal aorta was clamped. Duodenorrhaphy and
      aortic reconstruction with patch graft at the proximal suture line of aortic
      prosthesis was performed. Fortunately there was no pus, so tissue culture was not
      done. The intervention was concluded with an omentoplasty to protect the patch
      graft and to separate it from duodenorrhaphy. The patient did well after the
      surgical management. Because of the increasing number of elective aortic aneurysm
      repairs in the aging population, it is likely that more patients with secondary
      aortoenteric fistula will present to the clinical physicians in the future. So, a
      high index of suspicion is necessary for prompt diagnosis and treatment of this
      life-threatening event.

PMID- 18092032
TI  - Thunderclap headache associated with a nonhemorrhagic anaplastic
      oligodendroglioma.

PMID- 18092033
TI  - When medical care is financially conflicted.

PMID- 18092036
TI  - Ethics and evidence-based medicine: is there a conflict?
AB  - This article addresses the advantages, disadvantages, and traps to which evidence
      based medicine (EBM) may lead and suggests that, to be ethically valid, EBM must
      be aimed at the patient's best interests and not at the financial interests of
      others. While financial considerations are by no means trivial, it is
      hypocritical - if not dangerous - to hide them behind words like "evidence" or
      "quality."

PMID- 18092037
TI  - Functional dyspepsia and nonerosive reflux disease: clinical interactions and
      their implications.
AB  - Functional dyspepsia or nonulcer dyspepsia, and nonerosive reflux disease (NERD)
      or endoscopy-negative reflux disease, are common reasons for referral to a
      gastroenterologist. Although there is much confusion with regard to definition,
      recent research would suggest that these 2 conditions are linked and may
      represent components in the spectrum of the same disease entity, in terms of both
      symptoms and pathophysiology. Several theories have been proposed regarding the
      etiology of these disorders, including acid exposure, visceral hypersensitivity,
      impaired fundal accommodation, delayed gastric emptying, and Helicobacter pylori
      infection.

PMID- 18092038
TI  - A case of pancreatic lymphoma.

PMID- 18092039
TI  - Can psychiatric approaches help to address global warming?

PMID- 18092044
TI  - Medical student 'hazing' is unhealthy and unproductive.

PMID- 18092041
TI  - Treating the ocular component of allergic rhinoconjunctivitis and related eye
      disorders.
AB  - CONTEXT: Allergy symptoms that affect the eyes are common in adults and children
      worldwide, and are often associated with nasal allergy symptoms, prompting the
      term 'rhinoconjunctivitis' to describe the condition. However, this condition has
      not always been recognized, and earlier literature reported allergic
      conjunctivitis only within a subset of nasal allergy patients. EVIDENCE
      ACQUISITION: To assess the current state of ocular allergy epidemiology,
      pathophysiology, and currently available treatment options, we performed a
      MEDLINE search for articles regarding ocular allergy, rhinoconjunctivitis, vernal
      keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant
      papillary conjunctivitis (GPC). EVIDENCE SYNTHESIS: The more severe forms of
      ocular allergy are not only distressing, but can also threaten a patient's
      vision. Each type of ocular allergy is associated with ocular redness, itching,
      and tearing; however, AKC and VKC can threaten the cornea, and research has
      revealed that involvement of different immune cell populations (mast cells,
      eosinophils, and lymphocytes) may cause these more severe symptoms. A variety of
      treatment options exist to control ocular allergy symptoms. Nonpharmacologic
      options include allergen avoidance and lubrication with saline, and if these fail
      to be sufficiently effective, symptom relief may be provided by medicinal agents
      that are either applied topically to the eye or taken orally. Recent evidence
      suggests that nasal allergy treatments applied topically to the nose may also
      positively affect ocular allergy symptoms, which raises the interesting
      possibility that a parasympathetic nasal-ocular neural reflex pathway may be
      involved in the stimulation of allergic responses in the eye. CONCLUSIONS: Ocular
      allergy is underdiagnosed and has a significant impact on the life of the
      patient. It is vital to reach a better understanding of ocular allergic
      mechanisms and inflammation, which may lead to improved treatment.

PMID- 18092047
TI  - The Supreme Court and the Partial-birth Abortion Ban Act of 2003: a political
      procedure replaces woman-centered care.

PMID- 18092046
TI  - A systematic review of asthma and health literacy: a cultural-ethnic perspective
      in Canada.
AB  - BACKGROUND: Asthma is one of the most common inflammatory lung diseases and its
      prevalence and incidence have increased in many developed and developing
      countries. Asthma places a heavy burden on healthcare expenditures and
      productivity, which in turn diminishes the quality of life of the individuals
      involved as well as their families. The goal of improving a patient's knowledge
      about asthma management should include the enhancement of the individual's skills
      with the hopeful outcome of improving how the individual manages the condition.
      However, when health professionals prepare a training program, they are faced
      with the challenging cosmopolitan reality of individuals with different ethnic
      backgrounds. METHODS: In order to find links between asthma and health literacy
      in a cultural/ethnicity perspective, we performed a systematic review of all
      publications on the topic of asthma, health, and literacy among cultural groups
      from 1980 to 2006 using the Internet and journals: Medline (Ovid), ERIC, EMBASE,
      PsycINFO, Google, Google Scholar, Sociological Abstracts, and Anthropology Plus.
      Key words included the following: "asthma," "culture," "ethnicity," "literacy,"
      "health," "health literacy," "health beliefs," "adults," "disease management,"
      "chronic condition," "ethnocultural groups," "minority groups," and
      "newcomers/immigrants." RESULTS: More than 650 articles were initially identified
      in our review; 65 met our inclusion criteria. From these, we examined the factors
      related to asthma and literacy/health literacy with a cultural lens. All of these
      are categorized and summarized below. We chose what we considered to be the most
      relevant and important articles/documents in the research literature to date.
      Because many of the studies were qualitative, a formal meta-analytic review was
      not undertaken. We found that current asthma management techniques - including
      patient education - are not culturally sensitive, linguistically sensitive, or
      relevant, which creates further difficulties for ethnocultural communities and
      minority groups in many Western countries. In this systematic review, several
      themes were identified, including: approaches to language limitation and cultural
      barriers; the recognition of healthcare system bias (in terms of culturally
      competent care); and relationship-building to facilitate participatory decision
      making by both provider and patient. This review provides further understanding
      and considerations regarding the beliefs and perspectives of care providers and
      populations in relation to health and illness, literacy and health literacy, and
      their association with asthma among ethnocultural communities. CONCLUSIONS: There
      is an urgent need to better define the impact of cultural and ethnic issues in
      the management of asthma in Canada. Appropriately designed studies should better
      define the barriers in the optimal delivery of asthma care influenced by these
      parameters.

PMID- 18092048
TI  - "What personality type are you?".

PMID- 18092051
TI  - Expression of cyclooxygenase-2 and transforming growth factor-beta1 in HCV
      induced chronic liver disease and hepatocellular carcinoma.
AB  - Cyclooxygenase-2 (COX-2) and transforming growth factor-beta1 (TGF-beta1) were
      modulated in a variety of viral infections, but there is a paucity of data about
      their role in the pathologic process of cirrhosis and/or hepatocellular carcinoma
      (HCC) following chronic hepatitis C virus (HCV) infection. The material of the
      current study included 50 cases of chronic hepatitis C (CHC) without cirrhosis,
      30 cases of CHC with cirrhosis, and 30 cases of HCC with HCV admitted to the
      Gastroenterology and Hepatology Department of Theodor Bilharz Research Institute,
      Giza, Egypt. Fifteen wedge liver biopsies, taken during laparoscopic
      cholecystectomy, were included in the study as normal controls. Laboratory
      investigations, serologic markers for viral hepatitis, and serum alpha
      fetoprotein levels (alpha-FP) were done for all cases of the study.
      Immunohistochemistry using primary antibodies against both factors revealed weak
      to faint immunoreactivity to COX-2 and TGF-beta1 in normal hepatic tissue (< 30%
      and < 50% of the cells, respectively). COX-2 expression was upregulated in
      patients with CHC with and without cirrhosis, yet 80% of positively stained
      cirrhotic cases showed marked staining intensity. Higher COX-2 expression was
      observed in well-differentiated HCC cases (80%) with marked staining intensity
      (75%) compared with advanced HCC tumors (P < .001). TGF-beta1 was expressed in
      the hepatocytes of all cases of CHC with and without cirrhosis as well as in 67%
      of HCC cases. Extensive cytoplasmic expression was detected in 52%, 93.3%, and
      46.6% of CHC patients without cirrhosis, patients with cirrhosis, and patients
      with HCC, respectively. A positive correlation was observed between hepatic
      expression of COX-2 and TGF-beta1 (r = 0.67, P < .05); however, no correlation
      was detected between the latter and grade of HCC differentiation (r = 0.33, P >
      .05). CONCLUSION: These findings may suggest that TGF-beta1 plays a role in
      hepatic cell damage following HCV infection thus stressing the usefulness of this
      cytokine as a prognostic marker for liver cell injury. However, COX-2 is a
      predictive marker for malignant transformation and has a role in the early stages
      of hepatocarcinogenesis, but not in the advanced stages. The combined expression
      of both factors in HCV-related HCC suggests their synergistic action in the
      pathophysiology of hepatocarcinogenesis.

PMID- 18092053
TI  - The training of the "helpless" physician.

PMID- 18092054
TI  - The FDA alert on serotonin syndrome with combined use of SSRIs or SNRIs and
      Triptans: an analysis of the 29 case reports.
AB  - BACKGROUND: On July 19, 2006, the US Food and Drug Administration (FDA) issued an
      alert, "Potentially Life-Threatening Serotonin Syndrome With Combined Use of
      SSRIs or SNRIs and Triptan Medications." However, the cases that were the basis
      for the alert were not made available. The FDA recommends that patients treated
      concomitantly with a triptan and a selective serotonin reuptake inhibitor
      (SSRI)/selective norepinephrine reuptake inhibitor (SNRI) be informed of the
      possibility of serotonin syndrome. METHODS: Following a Freedom of Information
      Act request, the FDA provided the 29 cases that they evaluated as the basis for
      the alert. I summarize the cases, rate the quality of the cases on the basis of
      the information provided, and then determine whether the cases fulfill the
      Sternbach and Hunter criteria for serotonin syndrome. RESULTS: Seven cases met
      the Sternbach criteria but did not meet the Hunter criteria. No cases met both
      criteria or just the Hunter criteria. CONCLUSIONS: Triptans when administered
      with SSRIs or SNRIs might rarely precipitate serotonin syndrome. The data do not
      support prohibiting the use of triptans with SSRIs or SNRIs. With increased
      physician awareness of serotonin syndrome, it is possible that additional cases
      may be reported.

PMID- 18092055
TI  - Why don't the doctors attend the funerals of their patients who die?

PMID- 18092058
TI  - Dosing medical marijuana: rational guidelines on trial in Washington State.

PMID- 18092059
TI  - An 11-month-old boy with chronic diarrhea, failure to thrive, and hepatomegaly.

PMID- 18092063
TI  - It's hard for many people to follow a diet just from reading a book and a few
      sessions with a dietitian.

PMID- 18092060
TI  - Do bartonella infections cause agitation, panic disorder, and treatment-resistant
      depression?
AB  - INTRODUCTION: Bartonella is an emerging infection found in cities, suburbs, and
      rural locations. Routine national labs offer testing for only 2 species, but at
      least 9 have been discovered as human infections within the last 15 years. Some
      authors discuss Bartonella cases having atypical presentations, with serious
      morbidity considered uncharacteristic of more routine Bartonella infections. Some
      atypical findings include distortion of vision, abdominal pain, severe liver and
      spleen tissue abnormalities, thrombocytopenic purpura, bone infection, arthritis,
      abscesses, heart tissue and heart valve problems. While some articles discuss
      Bartonella as a cause of neurologic illnesses, psychiatric illnesses have
      received limited attention. Case reports usually do not focus on psychiatric
      symptoms and typically only as incidental comorbid findings. In this article, we
      discuss patients exhibiting new-onset agitation, panic attacks, and treatment
      resistant depression, all of which may be attributed to Bartonella. METHODS:
      Three patients receiving care in an outpatient clinical setting developed acute
      onset personality changes and agitation, depression, and panic attacks. They were
      retrospectively examined for evidence of Bartonella infections. The medical and
      psychiatric treatment progress of each patient was tracked until both were
      significantly resolved and the Bartonella was cured. RESULTS: The patients
      generally seemed to require higher dosing of antidepressants, benzodiazepines, or
      antipsychotics in order to function normally. Doses were reduced following
      antibiotic treatment and as the presumed signs of Bartonella infection remitted.
      All patients improved significantly following treatment and returned to their
      previously healthy or near-normal baseline mental health status. DISCUSSION: New
      Bartonella species are emerging as human infections. Most do not have antibody or
      polymerase chain reaction (PCR) diagnostic testing at this time. Manual
      differential examinations are of unknown utility, due to many factors such as low
      numbers of infected red blood cells, the small size of the infecting bacteria,
      uncertainty of current techniques in viewing such small bacteria, and limited
      experience. As an emerging infection, it is unknown whether Bartonella occurrence
      in humans worldwide is rare or common, without further information from
      epidemiology, microbiology, pathology, and treatment outcomes research.
      CONCLUSION: Three patients presented with acute psychiatric disorders associated
      with Bartonella-like signs and symptoms. Each had clear exposure to ticks or
      fleas and presented with physical symptoms consistent with Bartonella, eg, an
      enlarged lymph node near an Ixodes tick bite and bacillary angiomatosis found
      only in Bartonella infections. Laboratory findings and the overall general course
      of the illnesses seemed consistent with Bartonella infection. The authors are not
      reporting that these patients offer certain proof of Bartonella infection, but we
      hope to raise the possibility that patients infected with Bartonella can have a
      variety of mental health symptoms. Since Bartonella can clearly cause neurologic
      disorders, we feel the presence of psychiatric disorders is a reasonable
      expectation.

PMID- 18092064
TI  - Medication nonadherence: an unrecognized cardiovascular risk factor.
AB  - Nonadherence with prescribed drug regimens is a pervasive medical problem.
      Multiple variables affecting physicians and patients contribute to nonadherence,
      which negatively affects treatment outcomes. In patients with hypertension,
      medication nonadherence is a significant, often unrecognized, risk factor that
      contributes to poor blood pressure control, thereby contributing to the
      development of further vascular disorders such as heart failure, coronary heart
      disease, renal insufficiency, and stroke. Analysis of various patient populations
      shows that choice of drug, use of concomitant medications, tolerability of drug,
      and duration of drug treatment influence the prevalence of nonadherence.
      Intervention is required among patients and healthcare prescribers to increase
      awareness of the need for improved medication adherence. Within this process, it
      is important to identify indicators of nonadherence within patient populations.
      This review examines the prevalence of nonadherence as a risk factor in the
      management of chronic diseases, with a specific focus on antihypertensive
      medications. Factors leading to increased incidence of nonadherence and the
      strategies needed to improve adherence are discussed. Medication nonadherence,
      defined as a patient's passive failure to follow a prescribed drug regimen,
      remains a significant concern for healthcare professionals and patients. On
      average, one third to one half of patients do not comply with prescribed
      treatment regimens.[1-3] Nonadherence rates are relatively high across disease
      states, treatment regimens, and age groups, with the first several months of
      therapy characterized by the highest rate of discontinuation.[3] In fact, it has
      recently been reported that low adherence to beta-blockers or statins in patients
      who have survived a myocardial infarction results in an increased risk of
      death.[4] In addition to inadequate disease control, medication nonadherence
      results in a significant burden to healthcare utilization - the estimated yearly
      cost is $396 to $792 million.[1] Additionally, between one third and two thirds
      of all medication-related hospital admissions are attributed to
      nonadherence.[5,6]Cardiovascular disease, which accounts for approximately 1
      million deaths in the United States each year, remains a significant health
      concern.[7] Risk factors for the development of cardiovascular disease are
      associated with defined risk-taking behaviors (eg, smoking), inherited traits
      (eg, family history), or laboratory abnormalities (eg, abnormal lipid panels).[7]
      A significant but often unrecognized cardiovascular risk factor universal to all
      patient populations is medication nonadherence; if a patient does not regularly
      take the medication prescribed to attenuate cardiovascular disease, no potential
      therapeutic gain can be achieved. Barriers to medication adherence are
      multifactorial and include complex medication regimens, convenience factors (eg,
      dosing frequency), behavioral factors, and treatment of asymptomatic
      conditions.[2] This review highlights the significance of nonadherence in the
      treatment of hypertension, a silent but life-threatening disorder that affects
      approximately 72 million adults in the United States.[7] Hypertension often
      develops in a cluster with insulin resistance, obesity, and hypercholesterolemia,
      which contributes to the risk imposed by nonadherence with antihypertensive
      medications. Numerous strategies to improve medication adherence are available,
      from enhancing patient education to providing medication adherence information to
      the healthcare team and will be discussed in this article.

PMID- 18092065
TI  - ST segment elevation on electrocardiogram: the electrocardiographic pattern of
      Brugada syndrome.
AB  - A 77-year-old white diabetic woman was brought to our emergency department (ED)
      after becoming lightheaded and hypotensive at home. Her routine tests including a
      chest radiograph were normal. Her electrocardiogram (ECG) showed significant ST
      segment elevation in leads V1 to V4. Serial cardiac enzymes and troponin were
      within normal limits. Her ECG met the criteria for type 1 Brugada syndrome.
      Brugada syndrome, which is more common in young Asian males, is an arrhythmogenic
      disease caused in part by mutations in the cardiac sodium channel gene SCN5A. To
      diagnose the Brugada syndrome, 1 ECG criterion and 1 clinical criterion should
      exist. Brugada syndrome can be associated with ventricular tachycardia or
      fibrillation; the only treatment proven to prevent sudden death is placement of
      an implantable cardioverter defibrillator, which is recommended in symptomatic
      patients or in those with ventricular tachycardia induced during
      electrophysiologic studies and a type 1 ECG pattern of Brugada syndrome. It is
      important to recognize the Brugada ECG pattern and to differentiate it from other
      etiologies of ST segment elevation on ECG.

PMID- 18092068
TI  - Tuberculosis and HIV-needed: a new paradigm for the control and management of
      linked epidemics.

PMID- 18092069
TI  - Activity/participation limitation and weight loss among overweight and obese US
      adults: 1999 to 2002 NHANES.
AB  - OBJECTIVE: To examine the prevalence and association of activity/participation
      limitation with trying to lose weight and weight loss practices (eating fewer
      calories, physical activity, or both) among overweight and obese adults in the
      United States. RESEARCH METHODS AND PROCEDURES: Eligible adults were 20 years of
      age or older with a body mass index (BMI) >or= 25 kg/m(2) (n = 5608) who
      responded to standard physical functioning questions included in the 1999-2002
      National Health and Nutrition Examination Survey, a continuous survey of the
      civilian non-institutionalized US population. RESULTS: Obese (BMI >or= 30) men
      with vs. without activity/participation limitations were more likely to try to
      lose weight (OR = 1.59, 95% CI 1.05-2.41). This was not the case for overweight
      women and men (BMI 25-29.9), or obese women. Among adults trying to lose weight,
      reducing calorie consumption was common (63%-73%, men, 67%-76%, women).
      Overweight women with vs without activity/participation limitations had
      significantly reduced likelihood of attaining recommended physical activity (OR =
      0.56, 95% CI 0.36-0.89). Obese adults were more likely to try to lose weight if
      they attributed their limitation to body weight (OR = 1.78, 95% CI 1.11-2.88) or
      diabetes (OR = 1.86, 95% CI 1.01-3.43) compared to other causes. Overweight and
      obese adults who attributed activity/participation limitations to mental health,
      musculoskeletal, or cardiovascular problems were equally likely to attempt weight
      loss when respondents with each condition were compared to respondents without
      the condition. DISCUSSION: These results verify the importance of adequate
      subjective health assessment when developing individual weight loss plans, and
      may help guide weight management professionals in the development and delivery of
      more personalized care.

PMID- 18092070
TI  - A man with rheumatoid arthritis and iron-deficiency anemia.

PMID- 18092073
TI  - Asymmetrical supramolecular interactions as basis for complex responsive
      macromolecular architectures.
AB  - Intrigued by natural responsive systems based on a combination of macromolecules
      and non-covalent interactions, polymer scientists have mimicked such systems by
      the formation of supramolecular polymers based on ionic interaction, hydrogen
      bonding and metal coordination. In recent years, the focus has shifted from
      rather simple non-directional and self-complementary interactions to the use of
      asymmetrical directional supramolecular interactions that allow the formation of
      complex responsive macromolecular architectures such as block copolymers, star
      shaped polymers and graft copolymers. This feature article covers these recent
      developments on the use of asymmetrical supramolecular interactions in polymer
      science. Special attention is given to the formation of complex macromolecular
      architectures using directional supramolecular interactions. In addition, the
      responsiveness of the resulting macromolecular systems is discussed based on the
      assembly and/or disassembly that can be triggered by changes in external
      conditions.

PMID- 18092074
TI  - Vertically-aligned carbon nanotubes infiltrated with temperature-responsive
      polymers: smart nanocomposite films for self-cleaning and controlled release.
AB  - We have demonstrated that the infiltration of temperature-responsive polymers
      (e.g., PNIPAAm) into vertically-aligned carbon nanotube forests created
      synergetic effects, which provided the basis for the development of smart
      nanocomposite films with temperature-induced self-cleaning and/or controlled
      release capabilities.

PMID- 18092072
TI  - Biochemical applications of ultrathin films of enzymes, polyions and DNA.
AB  - This feature article summarizes recent applications of ultrathin films of enzymes
      and DNA assembled layer-by-layer (LbL). Using examples mainly from our own
      research, we focus on systems developed for biocatalysis and biosensors for
      toxicity screening. Enzyme-poly(L-lysine) (PLL) films, especially when stabilized
      by crosslinking, can be used for biocatalysis at unprecedented high temperatures
      or in acidic or basic solutions on electrodes or sub-micron sized beads. Such
      films have bright prospects for chiral synthesis and biofuel cells. Excellent
      bioactivity and retention of enzyme structure in these films facilitates their
      use in detailed kinetic studies. Biosensors and arrays employing DNA-enzyme films
      show great promise in predicting genotoxicity of new drug and chemical product
      candidates. These devices combine metabolic biocatalysis, reactive metabolite-DNA
      reactions, and DNA damage detection. Catalytic voltammetry or
      electrochemiluminescence (ECL) can be used for high throughput arrays utilizing
      multiple LbL "spots" of DNA, enzyme and metallopolymer. DNA-enzyme films can also
      be used to produce nucleobase adduct toxicity biomarkers for detection by LC-MS.
      These approaches provide valuable high throughput tools for drug and chemical
      product development and toxicity prediction.

PMID- 18092075
TI  - Zinc oxide nanonail based chemical sensor for hydrazine detection.
AB  - Using ZnO nanonails, a hydrazine electrochemical sensor has been fabricated, for
      the first time, which showed a high and reproducible sensitivity of 8.56 microA
      cm(-2) microM(-1) with a response time less than 5 s, a linear range from 0.1 to
      1.2 microM and a correlation coefficient of R = 0.999. The limit of detection
      (LOD), based on the S/N ratio, was estimated to be 0.2 microM.

PMID- 18092076
TI  - Chain-like assembly of gold nanoparticles on artificial DNA templates via 'click
      chemistry'.
AB  - We present a new type of azide-functionalized gold nanoparticle and their
      coupling to an alkyne-modified DNA duplex using the copper(I)-catalyzed Huisgen
      cycloaddition ('click chemistry'), resulting in a chain-like assembly of
      nanoparticles on the DNA template.

PMID- 18092077
TI  - Thiocarbonyl induced heterocumulenic Pauson-Khand type reaction: expedient
      synthetic method for thieno[2,3-b]indol-2-ones.
AB  - The first examples of C[double bond, length as m-dash]S induced Pauson-Khand type
      reactions are described; 2-alkynylphenyl isothiocyanates were converted to 3
      substituted-2H-thieno[2,3-b]indol-2-ones in the presence of a stoichiometric
      amount of Mo(CO)(6) or Co(2)(CO)(8), or a catalytic amount of Rh catalyst under
      an atmospheric pressure of carbon monoxide.

PMID- 18092078
TI  - Oxidation by CO2 of Au0 species on La2O3-supported gold clusters.
AB  - The IR spectra that characterize La(2)O(3)-supported gold clusters show that the
      original Au(0) species can be oxidized by CO(2) during the catalytic CO oxidation
      reaction, indicating that CO(2) is the actual gold oxidizing agent.

PMID- 18092079
TI  - A fast synthetic route to GDP-sugars modified at the nucleobase.
AB  - The direct structural modification of GDP-mannose via the bromination and Suzuki
      Miyaura cross-coupling of the unprotected sugar-nucleotide, to produce 8
      substituted fluorescent analogues of GDP-mannose.

PMID- 18092080
TI  - Thermodynamics of dimerization in solution as a rational tool for inducing
      nematic vs. smectic organizations in lanthanidomesogens.
AB  - The judicious tuning of simple thermodynamic parameters controlling dimerization
      processes in solution induces a rational switch between smectic and nematic
      organizations in thermotropic lanthanide-containing liquid crystals.

PMID- 18092081
TI  - A beta-diketiminato hydroxyphosphenium cation: phosphinous acid-secondary
      phosphine oxide tautomerism revisited.
AB  - The first example of a beta-diketiminato-supported hydroxyphosphenium cation has
      been prepared, structurally characterized, and modeled by DFT calculations.

PMID- 18092082
TI  - Transamination chemistry of sodium TMP-zincate: synthesis and crystal structure
      of a chiral amidozincate.
AB  - In a new type of reactivity for sodium TMP-zincate [(TMEDA)NaZn((t)Bu)(2)(TMP)]
      (1), transamination reactions with the amines diisopropylamine, DA(H),
      hexamethyldisilazane, HMDS(H) and chiral (R)-N-benzyl-alpha-methylbenzylamine
      have produced new sodium amido-di-tert-butyl zincates (all structurally
      characterised) with concomitant loss of TMP(H).

PMID- 18092083
TI  - Biodegradable microcapsules designed via 'click' chemistry.
AB  - Dextrans modified with alkyne and azide groups through hydrolysable carbonate
      esters form degradable microcapsules after Cu(I) catalysed 'click' reaction
      between azides and alkynes yielding triazole cross-links.

PMID- 18092084
TI  - Diastereoselective synthesis and spin-dependent photodecarbonylation of di(3
      phenyl-2-pyrrolidinon-3-yl)ketones: synthesis of nonadjacent and adjacent
      stereogenic quaternary centers.
AB  - A diastereoselective procedure to obtain N-para-methoxybenzyl bis-alpha,alpha'-3
      (3-phenyl-2-pyrrolidinone)yl substituted ketones with non-adjacent quaternary
      stereocenters, DL-2 and meso-3 was followed by a photoinduced, spin-dependent,
      and diastereoselective decarbonylation to give compounds DL-4 and meso-5, with
      adjacent all-carbon quaternary stereogenic centers.

PMID- 18092085
TI  - Water-soluble amphiphilic gold nanoparticles with structured ligand shells.
AB  - Highly water-soluble mixed monolayer protected "rippled" gold nanoparticles were
      synthesized through a one step reaction with sodium 11-mercaptoundecanesulfonate
      and octanethiol ligands at various ratios.

PMID- 18092086
TI  - Crabtree's catalyst revisited; ligand effects on stability and durability.
AB  - The extent of time-dependent deactivation of monophosphine monoamine iridium
      hydrogenation catalysts by trimer formation is strongly dependent on ligand
      structure; attempts to counter this process lead to the observation of an
      oligomerisation resistant catalyst.

PMID- 18092087
TI  - Direct synthesis of porous organosilicas containing chiral organic groups within
      their framework and a new analytical method for enantiomeric purity of
      organosilicas.
AB  - Organosilica porous solids containing chiral organic moieties in the framework
      with an enantiomeric purity of 95% ee, estimated by eluting organic constituent
      units from chiral organosilicas, were synthesized from a newly designed chiral
      (R)-(+)-1,2-bis(trimethoxysilyl)phenylethane precursor via a surfactant-mediated
      self-assembly approach.

PMID- 18092088
TI  - Synthesis and reactions of beta-diketiminato divanadium(I) inverted-sandwich
      complexes.
AB  - Reduction of VCl(2)(Nacnac) (Nacnac = HC(C(Me)NC(6)H(3)-iPr(2))(2)) with KC(8) in
      toluene leads to the formation of a toluene-bridged inverted-sandwich
      divanadium(I) complex, (mu-eta(6):eta(6)-C(7)H(8))[V(Nacnac)](2), which behaves
      as a source of V(Nacnac) and a multi-electron reductant in the two reactions
      studied in this report.

PMID- 18092089
TI  - Construction of N-1H,1H-perfluoroalkylated peptide bonds.
AB  - The preparation of a variety of optically pure peptides containing an N-1H,1H
      perfluoroalkyl label on a selected backbone amide bond is now possible.

PMID- 18092090
TI  - Exceptionally strong electronic coupling between [Mo2] units linked by
      substituted dianionic quinones.
AB  - Ligands derived from N-CH(3) substituted benzoquinonemonoimines are exceedingly
      good facilitators of electronic communication between two quadruply bonded
      dimolybdenum units and provide record values for comproportionation constants.

PMID- 18092091
TI  - Identification of productive inhibitor binding orientation in fatty acid amide
      hydrolase (FAAH) by QM/MM mechanistic modelling.
AB  - Modelling of the mechanism of covalent adduct formation by the inhibitor O
      arylcarbamate URB524 in FAAH shows that only one of the two possible inhibitor
      binding orientations is consistent with the experimentally observed irreversible
      carbamoylation of the nucleophile serine: this is a potentially crucial insight
      for designing new covalent inhibitors of this promising drug target.

PMID- 18092092
TI  - Solid-state highly fluorescent diphenylaminospirobifluorenylfumaronitrile red
      emitters for non-doped organic light-emitting diodes.
AB  - Bright (maximum 11,000 cd m(-2) and 500 cd m(-2) at 20 mA cm(-2)) and efficient
      (maximum external quantum efficiency of 3.1% at 1 mA cm(-2)) red (CIE, x = 0.66,
      y = 0.34) organic light-emitting diodes (OLEDs) employ arylaminospirobifluorene
      substituted fumaronitriles as the novel non-dopant red emitter.

PMID- 18092093
TI  - Chemo- and enantioselective sulfoxidation of bis(ethylenedithio)
      tetrathiafulvalene (BEDT-TTF) into chiral BEDT-TTF-sulfoxide.
AB  - Selective sulfoxidation of BEDT-TTF (bis(ethylenedithio)-tetrathiafulvalene) with
      enantiopure (camphoryl-sulfonyl)oxaziridine derivatives provided the inner
      monosulfoxide, as demonstrated using single crystal X-ray analysis, with an
      enantiomeric excess of 44% (up to 74% after recrystallization).

PMID- 18092094
TI  - Crystalline inclusion complex of a calixarene with a nitroxide.
AB  - The first capsular crystalline inclusion complex of para-hexanoyl calix[4]arene
      with stable nitroxyl radical DEPN has been isolated and showed a low mobility of
      the radical in the capsule.

PMID- 18092095
TI  - Using ionic liquids to trap unique coordination environments: polymorphic
      solvates of ErCl3(OH2)(4).2([C2mim]Cl).
AB  - Two polymorphs of ErCl(3)(OH(2))(4).2([C(2)mim]Cl) solvates were isolated from
      the same solution of 1-ethyl-3-methylimidazolium chloride when HCl(aq) was added,
      while [C(2)mim](3)[ErCl(6)] was isolated without HCl addition, illustrating how
      ionic liquids can be used to trap unusual coordination environments in the solid
      state.

PMID- 18092096
TI  - Ligand design for the improvement of stability of metal complex.protein hybrids.
AB  - We have succeeded in improving the stability of Fe(Schiff-base).heme oxygenase
      (HO) hybrids by ligand design based on the crystal structure of Fe(N,N'
      bis(salicylidene)-3.4-diaminobenzene propionic acid).HO.

PMID- 18092098
TI  - Unprecedented carbon-carbon bond formation induced by photoactivation of a
      platinum(IV)-diazido complex.
AB  - UVA-induced photodecomposition of a Pt(IV)-diazido complex involves not only
      reduction to Pt(II) and N(2) release, but also O(2) evolution and formation of
      nitrene intermediates, whose trapping with (CH(3))(2)S gives rise to an unusual
      N,N'-bis(ethyl)sulfurousdiamide ligand in an apparently unprecedented process
      involving C-C bond formation.

PMID- 18092097
TI  - Synthesis and cytotoxicity of a cobaltcarbonyl-alkyne enkephalin bioconjugate.
AB  - A solid-phase synthesized propargyl derivative of the neuropeptide leucine
      enkephalin (Enk) reacts rapidly and quantitatively with Co(2)(CO)(8) to give the
      Co(2)(CO)(6)-alkyne labeled peptide , which is the first organometallic peptide
      bioconjugate to show significant toxicity against two different tumor cell lines.

PMID- 18092099
TI  - Alkynes as masked ylides: gold-catalysed intermolecular reactions of propargylic
      carboxylates with sulfides.
AB  - The in situ-generation of sulfur ylides by the gold-catalysed rearrangement of
      propargylic carboxylates in the presence of sulfides has resulted in highly
      efficient and novel transformations.

PMID- 18092100
TI  - PAMAM dendron-stabilised palladium nanoparticles: effect of generation and
      peripheral groups on particle size and hydrogenation activity.
AB  - Dendron stabilised Pd nanoparticles were prepared using the self-assembly of
      dendrons, which could catalyze a highly selective hydrogenation of dienes and
      acetylenes to monoenes.

PMID- 18092101
TI  - Development of an anodic substitution reaction system using acoustic
      emulsification.
AB  - The anodic substitution reaction proceeded smoothly without affecting the
      oxidation of the nucleophile in a one-step electrochemical operation using
      acoustic emulsification.

PMID- 18092102
TI  - Charge transport mediated by d-orbitals in transition metal complexes.
AB  - This communication reports an asymmetric charge transport with a large
      rectification ratio and finely featured NDR (negative differential resistance) by
      d-orbitals of a neutral ruthenium(ii) complex with a C(2) axis of symmetry.

PMID- 18092103
TI  - Reactivity of a coordinatively unsaturated Cp*Ru(kappa2-P,O) complex.
AB  - Whereas a new coordinatively unsaturated Cp*Ru(kappa(2)-P,O) complex (1a) forms
      adducts with two-electron donors (including sigma-H(2) and mu-N(2) ligands),
      double Si-H bond activation is observed upon treatment with Ph(2)SiH(2) or
      PhSiH(3), leading to the clean formation of products corresponding to the net
      insertion of a Ph(2)Si: or Ph(H)Si: fragment into the Ru-O bond of 1a.

PMID- 18092104
TI  - Catalytic ring expansion, contraction, and metathesis-polymerization of
      cycloalkanes.
AB  - Tandem dehydrogenation-olefin-metathesis catalyst systems, comprising a pincer
      ligated iridium-based alkane dehydrogenation catalyst and a molybdenum-based
      olefin-metathesis catalyst, are reported to effect the metathesis
      cyclooligomerization of cyclooctane and cyclodecane to give cycloalkanes with
      various carbon numbers, predominantly multiples of the substrate carbon number,
      and polymers.

PMID- 18092105
TI  - The first crystal structure of a monomeric phenoxyl radical: 2,4,6-tri-tert
      butylphenoxyl radical.
AB  - Crystals of the 2,4,6-tri-tert-butylphenoxyl radical have been isolated and
      characterized by X-ray diffraction, and calculations have been performed that
      give the distribution of spin density in the radical.

PMID- 18092106
TI  - An NBD fluorophore-based sensitive and selective fluorescent probe for zinc ion.
AB  - A novel NBD-derived fluorescent probe for Zn(2+) is described; the probe features
      ready availability, good water solubility, high sensitivity and selectivity, and
      ability to quantify the concentration of Zn(2+).

PMID- 18092107
TI  - Beta-blockers and the treatment of hypertension: it is time to move on.

PMID- 18092108
TI  - The role of insight into and beliefs about medicines of hypertensive patients.
AB  - OBJECTIVES: One aim of this study was to determine the level of knowledge and
      understanding of selected individuals about hypertension, as well as their
      beliefs and perceptions about medicines. The other purpose was to determine the
      medicines information provision system that these participants were exposed to.
      METHODS: Participants filled in the Beliefs about Medicines questionnaire and one
      on-one interviews were conducted. Participants gave informed consent and their
      health passports were examined. A focus-group discussion was held with some of
      the nurses at one of the local clinics. RESULTS: Participants believed their
      antihypertensive therapy was necessary for them to maintain their health.
      However, there was also a high level of concern about the undesirable effects of
      the medication. Most participants did not understand what hypertension is,
      however, they were aware of the consequences of uncontrolled blood pressure.
      There was no structured patient education system at the public clinic
      investigated. CONCLUSION: A knowledge gap existed which needed to be filled.
      Participants' concerns about the undesirable effects of antihypertensive therapy
      needed to be addressed. A structured medicines information provision system is
      required at the public clinic studied, to ensure that patients receive all the
      pertinent information about their condition, namely hypertension, and the
      prescribed therapy.

PMID- 18092109
TI  - Maternal deaths due to hypertensive disorders in pregnancy: Saving Mothers report
      2002-2004.
AB  - Hypertensive disorders of pregnancy (proteinuric hypertension, eclampsia, chronic
      hypertension, HELL P syndrome) are the commonest direct causes of maternal deaths
      in South Africa. Six hundred and twenty-eight (19.1%) of the 3 406 maternal
      deaths in a three-year period (2002-2004) were associated with hypertensive
      disorders of pregnancy. Cerebral complications, mainly cerebral haemorrhage, were
      the pathological causes of death in approximately 50% of the cases and eclampsia
      (convulsions in pregnancy associated with high blood pressure) was the commonest
      clinical condition leading to death from hypertension. Avoidable factors, missed
      opportunities and substandard care in all three categories of patient-related,
      administrative, and healthcare-related components were found by the assessors of
      the National Committee on Confidential Enquiries into Maternal Deaths to be
      prevalent in the majority of the deaths. Prevention of complications by lowering
      high blood pressure fairly rapidly, early referral of high-risk cases to experts
      in the field, and the proper use of resuscitation skills should reduce maternal
      mortality associated with hypertensive disorders of pregnancy.

PMID- 18092110
TI  - The relationship between level of androgenic hormones and coronary artery disease
      in men.
AB  - BACKGROUND: Previous studies have shown controversial results on the role of
      androgens in coronary artery disease (CAD). We performed this study to assess the
      relationship between androgen levels and selective coronary angiography (SCA)
      findings. METHODS: This study was conducted on 502 consecutive men who underwent
      SCA with different indications in our centre. Medical history and blood samples
      were taken from all subjects prior to angiography. Free testosterone (FREET) was
      measured with enzyme-linked immunosorbent assay, and total testosterone (TES)
      plus dehydroepiandrosterone sulfate (DHEA) were checked with radio-immunoassay.
      Total cholesterol, high- and low-density lipoprotein cholesterol (HDL and LDL),
      triglycerides, lipoprotein (a) [Lp(a)] and C-reactive protein (CRP) were also
      tested in all patients. Angiographic results were reported by two cardiologists
      and checked for intra- and inter-observer reliability, then interpreted as
      Gensini score, and on the basis of the number of segments involved. The
      relationships were assessed with the chi-square test, independent sample t-test,
      one-way analysis of variances, Pearson's correlation, and univariate and
      multivariate logistic regression tests. RESULTS: Eighty-three (16.5%) of the
      subjects had single-vessel disease, 108 (21.5%) had two-vesssel, 197 (39.2%) had
      three-vessel disease, and 114 (22.7%) had normal angiograms or minimal lesions.
      FREET, TES and DHEA in patients with significant CAD vs normal individuals were
      6.69 +/- 3.20 pg/ml, 16.60 +/- 6.66 nm/l and 113.38 +/- 72.9 microg/dl vs 7.12 +/
      3.58 pg/ml, 15.82 +/- 7.26 nm/l and 109.03 +/- 68.19 microg/ dl, respectively (p
      > 0.1). There was no correlation between the Gensini score or the number of
      involved segments and androgen levels. Triglyceride, total cholesterol, LDL and
      HDL cholesterol levels also had no correlation with androgenic hormones. However,
      FREET showed a negative correlation with Lp(a) and CRP (p = 0.01, r = -0.12; p =
      0.03, r = -0.096, respectively). Moreover, the level of DHEA was lower in
      diabetics (94.5 +/- 59.19 microg/dl vs 117.97 +/- 74.54 microg/dl, p = 0.004).
      CONCLUSIONS: There was no significant correlation between FREET, TES, DHEA and
      the presence or severity of CAD. Also, no correlation was found between androgen
      levels and triglyceride, total cholesterol, LDL and HDL cholesterol levels.

PMID- 18092111
TI  - Erdosteine ameliorates lung injury induced by transient aortic occlusion in rats.
AB  - The aim of this experimental study was to evaluate the protective effect of
      erdosteine on lung injury induced by ischaemia-reperfusion (IR) of the lower
      extremities of rats. Wistar albino rats (n = 21) were divided into three groups.
      In the IR group (n = 7), the aorta was cross-clamped for two hours, followed by
      one hour of reperfusion. In the erdosteine group (n = 7), animals were pretreated
      with erdosteine 100 mg/kg daily via gastric lavage, starting three days before
      aortic occlusion. In the control group (n 5 7), the lungs were removed and blood
      samples were taken immediately after sternotomy. No treatment was given in the
      control and IR groups. After both lungs were removed, biochemical parameters were
      measured and broncho-alveolar lavage (BAL ) assessment was made. MDA levels and
      MPO activities in the lung tissue were significantly reduced in the erdosteine
      group compared to the IR group. BAL assessment revealed decreased neutrophil
      counts in the erdosteine-treated group. Pretreatment of animals with erdosteine
      significantly attenuated transient aortic occlusion-induced remote lung injury,
      characterised by leukocyte accumulation and lipid peroxidation. The results
      suggest that erdosteine may be beneficial in amelioration of lung injury caused
      by IR.

PMID- 18092112
TI  - Does dipyridamole-induced ischaemia affect NT-proBNP secretion?
AB  - BACKGROUND: B-type natriuretic peptide (BNP) and the inactive amino-terminal pro
      B-type natriuretic peptide (NTproBNP) have a prognostic value in heart failure
      and in myocardial infarction. There has been some evidence that BNP and NT-proBNP
      can be used in the diagnosis of myocardial ischaemia by improving the sensitivity
      of exercise- stress testing. OBJECTIVE: To observe the relationship between
      dipyridamole- induced ischaemia and the secretion of NT-proBNP. METHODS: A total
      of 52 consecutive patients, referred for dipyridamole stress 99m Tc-sestamibi
      single-photon emission computed tomography (SPECT) myocardial perfusion imaging
      (MPI) to diagnose reversible ischaemia, were enrolled. NT-proBNP was determined
      at rest and one hour after infusion of dipyridamole. RESULTS: Of the 52 patients,
      25 had normal scans, 12 had scans with fixed defects (previous myocardial
      infarction with no inducible ischaemia) and 15 had reversible perfusion defects
      (inducible ischaemia). There was no correlation between ischaemia and resting NT
      proBNP, post-stress NT-proBNP and the change in NT-proBNP. There was a
      correlation between ejection fraction, ventricular volumes and resting NT-proBNP.
      CONCLUSIONS: NT-proBNP does not add to the diagnosis of myocardial ischaemia in
      dipyridamole stress MPI.

PMID- 18092113
TI  - Peri-operative plasma disappearance rate of indocyanine green after coronary
      artery bypass surgery.
AB  - Splanchnic ischaemia and hepatic dysfunction are severe complications after
      coronary artery bypass grafting (CABG) and lead to increased morbidity and
      mortality. Non-invasive determination of the indocyanine green (ICG) plasma
      disappearance rate (PDR) offers an opportunity for the early diagnosis of hepato
      splanchnic hypoperfusion. The aim of this study was to establish the
      postoperative time course of the ICG PDR in elective uncomplicated CABG surgery.
      After ethical approval and written informed consent, the data of 40 patients were
      analysed during this prospective study. Measurements of the ICG PDR and cardiac
      index (CI) in 40 patients undergoing elective CABG surgery were performed
      immediately after induction of anaesthesia, on admission to the ICU, six hours
      after admission to the ICU, and on the first postoperative day. Prior to surgery,
      baseline ICG PDR was 17.7 %/min (13.6-20.4) and baseline CI was 2.2 l/min/m(2)
      (1.9-2.4). All measurements after surgery showed a significantly higher PDR and
      cardiac index compared to the baseline measurements. The only patient with
      prolonged ICU treatment failed to show this increase in ICG PDR, although the CI
      did increase after surgery. We established normal values of ICG PDR after
      uncomplicated CABG surgery. The elevated ICG PDR observed in our patients was
      assumed to be an effect of an increased hepato-splanchnic blood flow due to an
      increase in the CI. Patients at risk of hepato-splanchnic hypoperfusion,
      displaying a missed increase or even a decrease in their ICG PDR after surgery
      might be at risk of hepatic hypoperfusion and in these selected patients the ICG
      PDR could serve as a tool to guide therapy or to select patients who might
      benefit from more invasive devices to monitor hepatosplanchnic perfusion and
      function.

PMID- 18092114
TI  - False aneurysm of the left ventricle following myocardial infarction: an unusual
      location.
AB  - A false aneurysm of the left ventricle that is in fact a contained rupture is
      rare. False aneurysms have been reported to be mostly at the posterior-basal and
      rarely at the apical segments of the left ventricle. Early surgical intervention
      is recommended because of the risk of rupture. This report describes the
      successful surgical management of two patients with false aneurysms of the left
      ventricle, located at the lateral wall and the inferior wall following a recent
      inferior and lateral-wall myocardial infarction.

PMID- 18092115
TI  - A case of takotsubo cardiomyopathy precipitated by lumiracoxib, a selective COX-2
      inhibitor.
AB  - Considerable controversy exists regarding the cardiovascular safety of COX-2
      inhibitors, both in patients with and without established cardiovascular disease.
      Currently, the major focus is on thrombotic complications presenting as
      myocardial infarction. I n this report, we present a case of takotsubo
      cardiomyopathy, also known as the apical ballooning syndrome, precipitated by the
      use of lumiracoxib. We are concerned that this might be the first case of COX-2
      inhibitor-induced apical ballooning syndrome and that more may follow.

PMID- 18092116
TI  - Coronary slow-flow phenomenon.
AB  - Slow flow of the contrast in normal coronary arteries is a relatively common
      finding in patients undergoing routine coronary angiography. The severest form of
      this phenomenon is known as no flow or TIMI and is uncommon, with life
      threatening consequences. We describe a case of slow flow in the left anterior
      descending artery of a female patient undergoing a diagnostic coronary angiogram.

PMID- 18092118
TI  - Surgical management of Takayasu's arteritis in children and adolescents.
AB  - There is little information on the surgical management of Takayasu's arteritis in
      children and adolescents. Information on 30 patients aged between eight and 17
      years was culled from a prospectively maintained database on the Vascular Service
      of the University of KwaZulu-Natal, Durban, South Africa. Twenty-one patients had
      involvement of the descending aorta; in 19, this was confined to the aorta (type
      2 disease). One had associated arch disease (type 3) and one had associated
      cardiac disease (type 4). One patient had isolated axillary artery occlusion
      (type 5). Eight patients had disease confined to the aortic arch (type 1), 22 had
      occlusive disease and eight were aneurysmal. All patients had operative repairs
      undertaken. There were no peri-operative deaths in the group who had
      cerebrovascular reconstruction, and one death (4.5%) in those who had descending
      aortic replacement. Patients were followed up for between one month and 11 years.
      Hypertension was improved or cured in 10 of 12 patients. Two died during this
      period and another five patients (20%) required further surgery for stenosis
      (three patients) or anastomotic aneurysms (two). CONCLUSION: Bypass surgery
      yields satisfactory results in this age group in terms of peri-operative and
      medium-term mortality and morbidity.

PMID- 18092117
TI  - Striving towards the ideal cardiac functional assessment strategy: the
      contribution of tissue Doppler, strain and strain rate imaging.
AB  - In cardiac research, a major goal of prevention of catastrophic events by risk
      factor management and earlier detection has, in recent years, led to a
      proliferation of imaging modalities, moving us from old-fashioned chest X-ray
      through increasingly sophisticated approaches such as magnetic resonance imaging
      (MRI) and multi-slice fast computer-aided tomography (CT) scanning. Today, we
      have the option of using a vast array of invasive and non-invasive approaches,
      with diverse technical underpinnings, to assess various, and often overlapping
      aspects of cardiac function. Tissue Doppler imaging (TDI) and the related
      applications of strain and strain rate imaging are new technologies that are now
      being evaluated in the realm of practical patient care, and the underlying
      principles remind us that cardiac contractility is a reflection of the
      integration of muscle fibre architecture, mechanics and metabolism. TDI is the
      first technology that allowed imaging of motion within the myocardial wall rather
      than that of the blood pool, and permits analysis of velocities and accelerations
      from ultrasonic scatterers in muscle. Since its inception, it has been used to
      evaluate both new cardiac functional parameters as well as conventional function;
      for some of these, TDI has proven the superior imaging modality, while for others
      it offers only incremental information over conventional approaches.

PMID- 18092119
TI  - Warfarin: a dauntingly interactional medication.

PMID- 18092120
TI  - Reducing ocular damage in type 2 diabetes: the FIELD study shows fenofibrate
      benefits.

PMID- 18092121
TI  - CORONA study highlights challenges of treating older patients with systolic heart
      failure.

PMID- 18092122
TI  - Distribution of mercury in surficial sediments from Todos Santos Bay, Baja
      California, Mexico.
AB  - During 2004 the spatial distribution of total Hg in sediments from Todos Santos
      Bay, Baja California, Mexico was studied to evaluate the degree of environmental
      impact in this bay. The results showed low concentrations and no Hg enrichment at
      any site. These findings suggest natural levels of Hg in the water of Todos
      Santos Bay. The regional distribution of Hg/Fe shows lower values in the East and
      higher in the West of the bay. No significant correlations (p<0.05) were found
      between Hg and organic matter or particle size, suggesting that the distribution
      of Hg is not controlled by these variables.

PMID- 18092123
TI  - Methylmalonic acid values in healthy Dutch children.
AB  - BACKGROUND: Plasma methylmalonic acid (MMA) is a specific marker for functional
      cobalamin deficiency. This deficiency can give rise to non-specific but serious
      symptoms in childhood such as developmental delay, convulsions and failure to
      thrive and may even lead to irreversible neurological damage. AIM OF THE STUDY:
      To analyse plasma MMA concentrations in Dutch children and to evaluate possible
      factors influencing its concentration. METHODS: A number of 186 Dutch children
      aged 0-19 years were analysed cross-sectionally. Blood was collected to measure
      MMA, total homocysteine (tHcy), cobalamin (Cbl) and serum creatinine
      concentrations. In addition, information about medical history, age and sex was
      recorded. RESULTS: The geometric mean (GM) plasma MMA concentration was 0.17
      micromol/l (95% CI 0.07-0.42) and the GM tHcy was 6.6 micromol/l (95% CI 3.1
      13.9). There is a slight positive correlation between plasma MMA and age in
      children >1 year (r = 0.211, P < 0.05). Plasma MMA concentrations were
      significantly higher in children with low Cbl concentrations. No significant
      difference in MMA, Cbl, tHcy or creatinine concentrations between sexes could be
      observed. Regression analysis showed that Cbl was the strongest determinant of
      plasma MMA (regression coefficient -0.414, P < 0.05). The association between MMA
      and Cbl is stronger at increasing age (P for trend 0.045). CONCLUSIONS: Plasma
      Cbl is the main determinant of MMA in this group of Dutch children. The strength
      of the association increased with increasing age.

PMID- 18092124
TI  - Pathogenesis of bovine spongiform encephalopathy in sheep.
AB  - The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied
      by immunohistochemical detection of scrapie-associated prion protein (PrP(Sc)) in
      the gastrointestinal, lymphoid and neural tissues following oral inoculation with
      BSE brain homogenate. First accumulation of PrP(Sc) was detected after 6 months
      in the tonsil and the ileal Peyer's patches. At 9 months postinfection, PrP(Sc)
      accumulation involved all gut-associated lymphoid tissues and lymph nodes as well
      as the spleen. At this time point, PrP(Sc) accumulation in the peripheral neural
      tissues was first seen in the enteric nervous system of the caudal jejunum and
      ileum and in the coeliac-mesenteric ganglion. In the central nervous system,
      PrP(Sc) was first detected in the dorsal motor nucleus of the nervus Vagus in the
      medulla oblongata and in the intermediolateral column in the spinal cord segments
      T7-L1. At subsequent time points, PrP(Sc) was seen to spread within the lymphoid
      system to also involve all non-gut-associated lymphoid tissues. In the enteric
      nervous system, further spread of PrP(Sc) involved the neural plexi along the
      entire gastrointestinal tract and in the CNS the complete neuraxis. These
      findings indicate a spread of the BSE agent in sheep from the enteric nervous
      system through parasympathetic and sympathetic nerves to the medulla oblongata
      and the spinal cord.

PMID- 18092125
TI  - Identical rearrangement of NSP3 genes found in three independently isolated virus
      clones derived from mixed infection and multiple passages of Rotaviruses.
AB  - Three rotavirus variants with a rearranged RNA segment derived from the NSP3 gene
      were isolated in three independent experiments of coinfection and multiple
      passages of simian rotavirus strain SA11 and single-VP7-gene- or NSP1-gene
      substitution reassortants having genetic background of SA11. Sequence analysis
      indicated that the three rearranged NSP3 genes had almost identical sequences and
      genomic structures organized by partial duplication of the open reading frame in
      a head-to-tail orientation following the termination codon. The junction site of
      the original NSP3 gene (first copy) and the duplicated portion (second copy) was
      identical among the three rearranged genes, while a direct repeat, i.e., a
      homologous sequence between the first copy and second template for duplication,
      typically located at the junction site, was not detected. However, short similar
      sequences were present at the end of the first copy and beginning of the second
      copy. These findings suggest that rearrangement of the NSP3 gene may occur at a
      certain preferential site which is related to sequence similarity between 3'
      untranslated region and a region near the 5'-end of ORF.

PMID- 18092126
TI  - Glycogen storage disease manifested as gout and myopathy: three case reports and
      literature review.
AB  - Glycogen storage diseases (GSDs) are a group of congenital inherited metabolic
      diseases. They may present the symptoms of muscle and joint which may be
      misdiagnosed with some rheumatic diseases. We report three cases of GSDs in order
      to have a more clear recognition of the disease and to discuss the differential
      diagnosis.

PMID- 18092127
TI  - Multicentric diffuse-type giant cell tumor of the hand.
AB  - Diffuse-type giant cell tumor (D-TGCT) is relatively rare. We report a case of
      multicentric D-TGCT located in the finger and wrist. A 79-year-old man presented
      with a more than two-year history of tumors. Marginal resection was performed.
      Histological study of the specimens disclosed D-TGCT. Recurrence occurred two
      years and five months postoperatively and was again excised. Clinical
      presentation, radiological features and histopathological findings are discussed
      with reference to the literature.

PMID- 18092128
TI  - Severe airflow limitation in two patients with systemic lupus erythematosus:
      effect of inhalation of anticholinergics.
AB  - Airway involvement clinically presenting as dyspnea and an obstructive
      ventilatory defect is a rare but clinically important complication in systemic
      lupus erythematosus (SLE), since the airway manifestation is often progressive
      and resistant to systemic immunosuppressive therapy. Here we report two SLE
      patients with slowly progressive airflow limitation, which was clinically thought
      to be bronchiolitis obliterans. Both patients showed obvious improvement after
      inhalation of anticholinergics was started. Because anticholinergics are highly
      safe and never immunosuppressive, inhalation of these drugs might be useful in
      the therapeutic strategies for airflow limitation accompanying SLE or other
      collagen diseases.

PMID- 18092130
TI  - Usefulness of 67Ga SPECT and integrated low-dose CT scanning (SPECT/CT) in the
      diagnosis of cardiac sarcoidosis.
AB  - OBJECTIVE: We performed 67Gallium (Ga) single-photon emission computed tomography
      (SPECT) with integrated low-dose computed tomography (CT) for the interpretation
      of myocardial outline to investigate the value of co-registered fusion imaging
      using a hybrid system (SPECT/CT) in patients with cardiac sarcoidosis. METHODS:
      SPECT/CT of the region in question was performed with VG Hawkeye. The subjects in
      this study were 37 patients [mean (+/-SD) age 61.0+/-13.0 years; 12 men and 25
      women], 13 of whom had a clinical diagnosis of cardiac sarcoidosis and 24 a
      negative diagnosis. An intravenous injection of Ga (dosage 111 MBq) was performed
      on patients 48 h or 72 h before obtaining static planar images of the whole-body
      and the SPECT/CT scan. RESULTS: Abnormal Ga uptake in the myocardium was observed
      in 10 of the 13 subjects with true sarcoidosis, and in 11 of 24 with negative
      sarcoidosis without CT fusion. The sensitivity without CT fusion was 77%, the
      specificity 54%, and the accuracy 62%. Use of SPECT/CT changed the diagnosis only
      in a patient with true sarcoidosis, and changed the diagnosis in eight patients
      with negative sarcoidosis. The sensitivity with CT fusion was 69%, the
      specificity 79%, and the accuracy 76%. The difference in diagnostic accuracy was
      statistically significant (McNemar's test, P=0.039). CONCLUSIONS: SPECT scanning
      using Ga and integrated low-dose CT is a very useful diagnostic imaging technique
      because it improves the diagnostic specificity of Ga SPECT to allow the highly
      specific diagnosis of cardiac sarcoidosis.

PMID- 18092129
TI  - Interleukin-17 gene expression in patients with rheumatoid arthritis.
AB  - Interleukin-17 is a proinflammatory cytokine. Recent animal studies have shown
      that IL-17 plays a role in the initiation and progression of arthritis. However,
      whether IL-17 has a prominent role in human rheumatoid arthritis (RA) or not
      remains unclear. Here we investigated the role of IL-17 in patients with RA. cDNA
      was prepared from knee joint synovial tissues of RA (n = 11) and osteoarthritic
      (OA, n = 10) patients and PBMC of RA (n = 52) and healthy subjects (n = 34). IL
      17 gene expression level was measured by real-time PCR, and was compared with
      various clinical parameters. IL-17 gene expression in synovial tissues of RA was
      similar to that in OA. IL-17 gene expression level in PBMC of RA patients was
      significantly higher than in the control. The response (changes in DAS) to two
      week treatment with anti-TNF-alpha blockers (infliximab or etanercept) did not
      correlate with changes in IL-17 gene expression levels. The IL-17/TNF-alpha gene
      expression ratio at baseline (before treatment) tended to be lower in responders
      to the treatment. Expression of IL-17 gene in PBMC may be associated with the
      inflammatory process of RA. IL-17/TNF-alpha expression ratio is a potentially
      suitable marker of response to anti-TNF-alpha therapy.

PMID- 18092131
TI  - Pre-operative estimation of esophageal tumor metabolic length in FDG-PET images
      with surgical pathology confirmation.
AB  - OBJECTIVE: The aim of this study was to evaluate a 3D tumor segmentation method
      for fluorodeoxyglucose positron emission tomography (FDG-PET) in the context of
      noninvasive estimation of tumor metabolic length (Lm), as it correlates with
      surgical pathology and phantom results. METHODS: Thirty-four patients (7 women,
      27 men) with esophageal cancer were retrospectively evaluated. All patients
      underwent FDG-PET-computed tomography (CT) imaging following endoscopic
      ultrasound (EUS). Seventeen patients had esophagectomy after PET/CT, without
      prior neoadjuvant therapy. Tumor length was assessed by EUS (Le, n=31) and
      histopathology (Lp, n=17). Images were evaluated quantitatively with a 3D
      threshold-based region-growing program (Medical Image Processing Analysis and
      Visualization). Lm, total metabolic volume (Vm), maximum standardized uptake
      value (SUVmax), and average SUV (SUVa) over the entire tumor were obtained for
      several threshold values (mean activity in the liver plus 0-, 1-, 2-, 3-, and 4
      SD of the activity in the liver). RESULTS: Lm showed a good correlation with Lp
      for all thresholds (best correlation for Lm(2-SD), r=0.74, P<0.001). A positive
      nonsignificant correlation was observed between Lp and Le (r=0.30, P=0.29). Lm(2
      SD) correlated well with Le (r=0.71, P<0.001). Good correlations were also
      observed between Lm(2-SD) and Vm(2-SD) (r=0.89, P<0.001) and SUVa(2-SD) (r=0.38,
      P<0.05). Vm(2-SD) also had a significant correlation with Lp (r=0.61, P<0.05) and
      Le (r=0.57, P<0.001). CONCLUSIONS: FDG-PET-derived tumor metabolic length of
      untreated esophageal carcinomas correlates well with surgical pathology results,
      and provides preliminary evidence that noninvasive delineation of the superior
      and inferior extent of viable tumor involvement might be feasible using computer
      generated metabolic length measurements.

PMID- 18092132
TI  - Benefits of quantitative gated SPECT in evaluation of perioperative cardiac risk
      in noncardiac surgery.
AB  - OBJECTIVE: Gated single-photon emission computed tomography (G-SPECT) was used to
      evaluate cardiac risk associated with noncardiac surgery and determine the
      benefits and indications of this technique for this type of surgery. MATERIALS
      AND METHODS: Patients scheduled to undergo noncardiac surgery under the
      supervision of anesthesiologists and subjected to preoperative cardiac evaluation
      using G-SPECT during the 26-month period between June 2000 and August 2002 were
      followed for the presence/absence of cardiac events (i.e., cardiac death,
      myocardial infarction, unstable angina, congestive heart failure, or fatal
      arrhythmia) during surgery and the postoperative period until discharged.
      Relationships between the occurrence of cardiac events and preoperative G-SPECT
      findings were evaluated. RESULTS: A total of 39 patients underwent G-SPECT; 6 of
      the 39 exhibited abnormal ejection fraction (left ventricular ejection fraction,
      LVEF<or=50%) and end-systolic volume (ESV>or=50 ml). Surgery was suspended for
      three of these six patients and cardiac events developed in the remaining three
      patients. Both abnormal perfusion images (PI) and abnormal wall thickening (WT)
      were observed in all six patients. All six patients exhibited abnormal LVEF
      and/or ESV. Three patients had either abnormal PI or WT, and a cardiac event
      occurred in one of them. Of the five patients who experienced cardiac events
      during or after surgery, two exhibited a short run of ventricular tachycardia
      requiring a continuous administering of antiarrhythmic drugs, whereas the
      remaining three patients exhibited cardiac failure requiring inotropic support
      following surgery. CONCLUSIONS: The results of this study indicate that the
      occurrence of perioperative cardiac events can be predicted by considering the
      severity of expected surgical stress and preoperative G-SPECT findings for LVEF,
      PI, and WT. We conclude that G-SPECT is quite useful for cardiac risk assessment
      in patients undergoing noncardiac surgery.

PMID- 18092133
TI  - Quantitative FDG-uptake by positron emission tomography in progressive
      hypertrophy of rat hearts in vivo.
AB  - BACKGROUND: Quantitative myocardial fluorodeoxyglucose positron emission
      tomography (FDG-PET) for assessing glucose uptake in vivo is reliable in normal
      rat heart. OBJECTIVE: To assess the applicability of myocardial FDG-PET on
      multiple occasions in the longitudinal disease process of progressive hypertrophy
      of rat heart. METHODS: Six salt-sensitive Dahl rats (Dahl-S) developing
      progressive hypertrophy with subsequent dilated cardiomyopathy were compared with
      salt-resistant Dahl rats (controls). FDG-PET was applied twice at early stage
      (ES: 14-18 weeks) and at late stage (LS: 22-26 weeks) of hypertrophy.
      Standardized uptake value (SUV) was calculated for comparing between different
      animal weights and different injection dosages of FDG. For validating the
      quantitative study, radioactivity of a total of 36 tissue samples was compared
      with the corresponding PET values. RESULTS: The left ventricular mass in Dahl-S
      increased by 17% at ES and by 25% at LS. The SUV in Dahl-S was 95% of controls at
      ES and reduced to 62% at LS (P=0.023). The heart function started to deteriorate
      after LS. Linear regression analysis showed a good correlation between the
      radioactivity of tissue samples and PET values (Y=1.20X, P<0.0001, R2=0.979).
      CONCLUSIONS: Small animal PET studies on longitudinal multiple occasions in vivo
      were feasible and useful for the repeating assessment of glucose uptake. The
      reduction of glucose uptake in progressive hypertrophy of heart over time may
      precede its progression to heart failure.

PMID- 18092134
TI  - Semi-quantitation of pulmonary perfusion heterogeneity on respiratory-gated
      inspiratory and expiratory perfusion SPECT in patients with pulmonary emphysema.
AB  - OBJECTIVE: Pulmonary perfusion heterogeneity (PPH) in pulmonary emphysema (PE)
      was semi-quantified by functional lung volume rate (FLVR) curves obtained from
      respiratory-gated inspiratory and expiratory single-photon emission computed
      tomography (SPECT). METHODS: Gated and ungated SPECT were obtained in 36 PE
      patients [25 with stage IIA and 11 with stage IIB for global initiative for
      chronic obstructive lung disease (GOLD) stage classification] and 12 controls,
      using a triple-head SPECT system and a respiratory tracking device. On gated
      SPECT, the voxel numbers calculated at the 10% cutoff threshold for the maximum
      lung radioactivity were assumed to be the functional lung volume of the lung (V).
      FLVR (%) was calculated as FLV divided by V at every additional 10% thresholds,
      yielding inspiratory and expiratory FLVR curves. The dissociations between these
      curves (DeltaFLVRinsp-exsp) and the total difference (D index) of these curves
      from the normal standard curve (averaged inspiratory and expiratory curve in
      controls) were calculated. D index and the extent of low attenuation area (%LAA)
      on CT were correlated with the transfer coefficient for carbon monoxide (KCO) in
      PE patients. RESULTS: Although gated and ungated SPECT showed fairly uniform
      perfusion in controls, gated SPECT-enhanced PPH compared with ungated SPECT in PE
      patients, with significantly higher dissociation (DeltaFLVRinsp-exsp) than that
      in controls (24.9%+/-9.5% vs. 4.5%+/-1.3%; P<0.0001). DeltaFLVRinsp-exsp was
      significantly higher even in stage IIA patients (P<0.0001). Expiratory D index
      was significantly higher than the inspiratory one in PE patients (P<0.01). This
      index was significantly higher in stage IIB patients than in stage IIA patients
      (44.1%+/-19.0% vs. 29.4%+/-13.7%; P<0.05), and was significantly correlated with
      KCO (R=0.642, P<0.0001) in all PE patients, although %LAA was not correlated with
      KCO. CONCLUSIONS: FLVR curve analysis on gated SPECT appears useful for semi
      quantitation of respiratory change of PPH in PE. Expiratory D index may better
      reflect the lung pathophysiology of PE than morphologic CT.

PMID- 18092135
TI  - Nonionic intravenous contrast agent does not cause clinically significant
      artifacts to 18F-FDG PET/CT in patients with lung cancer.
AB  - OBJECTIVE: This study was performed to evaluate the effects of intravenous (i.v.)
      contrast agent on semi-quantitative values and lymph node (LN) staging of 18F
      fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG
      PET/CT) in patients with lung cancer. METHODS: Thirty-five patients with lung
      cancer were prospectively included. Whole-body PET and nonenhanced CT images were
      acquired 60 min following the i.v. injection of 370 MBq 18F-FDG and subsequently,
      enhanced-CT images were acquired with the i.v. administration of 400 mg iodinated
      contrast agent without positional change. PET images were reconstructed with both
      nonenhanced and enhanced CTs, and the maximum and average standardized uptake
      values (SUVmax and SUVave) calculated from lung masses, LNs, metastatic lesions,
      and normal structures were compared. To evaluate the effects of the i.v. contrast
      agent on LN staging, we compared the LN status on the basis of SUVs (cut-offs;
      SUVmax=3.5, SUVave=3.0). RESULTS: The mean differences of SUVmax in normal
      structures between enhanced and nonenhanced PET/CT were 15.23%+/-13.19% for
      contralateral lung, 8.53%+/-6.11% for aorta, 5.85%+/-4.99% for liver, 5.47%+/
      6.81% for muscle, and 2.81%+/-3.05% for bone marrow, and those of SUVave were
      10.17%+/-9.00%, 10.51%+/-7.89%, 4.95%+/-3.89%, 5.66%+/-9.12%, and 2.49%+/-2.50%,
      respectively. The mean differences of SUVmax between enhanced and nonenhanced
      PET/CT were 5.89%+/-3.92% for lung lesions (n=41), 6.27%+/-3.79% for LNs (n=76),
      and 3.55%+/-3.38% for metastatic lesions (n=35), and those of SUVave were 3.22%+/
      3.01%, 2.86%+/-1.71%, and 2.33%+/-3.95%, respectively. Although one LN status
      changed from benign to malignant because of contrast-related artifact, there was
      no up- or down-staging in any of the patients after contrast enhancement.
      CONCLUSIONS: An i.v. contrast agent may be used in PET/CT without producing any
      clinically significant artifact.

PMID- 18092136
TI  - FDG-PET/CT findings of autoimmune pancreatitis associated with idiopathic
      retroperitoneal fibrosis.
AB  - We report the fluorodeoxyglucose positron emission tomography (FDG-PET)/computed
      tomography (CT) findings of autoimmune pancreatitis (AIP) associated with
      idiopathic retroperitoneal fibrosis. A 69-year-old male patient was admitted to
      our hospital with obstructive jaundice. Six months prior to this admission, he
      was treated with steroid therapy for retroperitoneal fibrosis. Laboratory data
      showed that elevated T-bil, C-reactive protein, amylase and immunoglobulin 4, and
      antinuclear antibodies were positive. Clinical history, laboratory data, CT
      image, and magnetic resonance imaging led to a diagnosis of autoimmune
      pancreatitis. To investigate the inflammatory activity, FDG-PET/CT was
      undertaken. FDG-PET/CT demonstrated diffuse intense FDG uptake in the enlarged
      pancreas and diffuse mild uptake in the region of the abdominal aorta-bilateral
      iliac arteries. A dilated right renal pelvis and upper ureter, corresponding to
      hydronephrosis probably caused by retroperitoneal fibrosis, were shown. An FDG
      PET/CT was useful to evaluate inflammatory activity and morphological imaging,
      and supported our diagnosis of AIP and retroperitoneal fibrosis.

PMID- 18092137
TI  - Evaluation of portosystemic shunt caused by patent ductus venosus through
      sequential whole-body scanning using per-sigmoid colon 123I-IMP scintigraphy.
AB  - OBJECTIVE: The correct estimation of the portosystemic shunt (PSS) ratio prior to
      surgery for patent ductus venosus is important. Until now, formulas using the
      lung and liver uptake for per-rectal portal scintigraphy using 123I
      iodoamphetamine (IMP) have been mainly used for calculating the PSS ratio.
      However, these methods did not take radioactivity in the brain or changes in
      organ radioactivity over time into consideration. Here, we performed sequential
      whole-body scanning by per-sigmoid colon 123I-IMP scintigraphy, and evaluated the
      changes in radioactivity in the liver, lungs, and brain over time. METHODS: The
      patient was 7-year-old boy with a patent ductus venosus. A 10 Fr. catheter was
      inserted into the sigmoid colon under fluoroscopic guidance, through which about
      55.5 MBq of 123I-IMP was administered. Following the administration, the patient
      was placed in the supine position and sequential whole-body scanning (from head
      to thigh) was performed for up to about 80 min. Four regions of interest (ROIs)
      were placed on the whole brain, lungs, liver, and mediastinum. The PSS ratios
      were calculated using both the traditional formula (PSS index: brain uptake is
      not considered) and our original formula (new index: brain uptake is considered).
      RESULTS: Prior to surgery, the radioactivity could be seen clearly in the brain
      and lungs just following the injection. The liver uptake was faint on the first
      and second scans (15 min/scan), and increased gradually over time. In contrast,
      almost no radioactivity was detected in the brain or lungs following surgery. The
      liver uptake could be seen clearly just following the injection. The new index
      was significantly higher than the PSS index. Both the new index and the PSS index
      showed changes over time especially prior to surgery. CONCLUSIONS: Distinct brain
      radioactivity was observed early following administration in a patient with PSS.
      The calculation of the PSS fraction should be performed taking the brain
      radioactivity into consideration. The timing of the scan should be fixed, but 30
      min following administration may be too early to begin scanning.

PMID- 18092138
TI  - Simple provocative maneuvers in renal transplant scintigraphy for detecting urine
      leak.
AB  - Urine leak in the early postoperative period following renal transplantation is a
      serious complication requiring early identification and aggressive intervention,
      which significantly reduces the morbidity and mortality. Renal transplant
      scintigraphy is a noninvasive method to evaluate the perfusion and function of a
      transplanted kidney and urinary drainage including urine leak. Here, we reported
      two cases in which the standard transplant renogram failed to demonstrate urine
      leak. The cases were referred for a diethylenetriaminepentaacetic acid renogram
      following the transplantation to evaluate the cause of symptoms or elevated serum
      creatinine level. In both the cases, urine leak was successfully detected
      following simple maneuvers such as diuretic administration or Foley catheter
      irrigation. Renal transplant scintigraphy is an effective and safe technique and
      the use of these simple maneuvers can enhance the diagnostic sensitivity of the
      transplant renogram in the detection of urine leak.

PMID- 18092139
TI  - SUV correction for injection errors in FDG-PET examination.
AB  - OBJECTIVE: Many studies have documented the clinical usefulness of standardized
      uptake values (SUV) for diagnosis. However, in the event of injection error,
      accurate measurements cannot be obtained if the radioactivity of
      fluorodeoxyglucose (FDG) leakage is not subtracted from the administered dosage.
      Here, a correction formula for radioactivity estimation that takes into account
      the radioactivity of FDG leakage was derived on the basis of a phantom
      experiment. Furthermore, to determine whether SUV could be accurately calculated
      by the correction formula, we performed a volunteer study. METHODS: Images were
      displayed by altering the conversion constant from 1.0, 0.1 to 0.01, and the
      range of correctable counts was verified on the basis of image inversion. To
      estimate the radioactivity of FDG leakage by imaging, the count of the leakage
      was measured, converted into a radioactivity concentration using a cross
      calibration factor (CCF), and multiplied by volume, as measured by imaging. Three
      factors that markedly affect count, i.e., count rate performance, partial volume
      effect and crosstalk, were assessed in phantom studies in order to derive a
      correction formula. In addition, to clarify the accuracy of the correction
      formula, we attached to the right elbow. RESULTS: With a conversion constant of
      0.1, there was no image inversion at <or=1.565 MBq/ml. At concentrations below
      this, the average detection rate was 90%. This suggests that count rate
      performance can be corrected at <or=1.0 MBq/ml. Crosstalk investigations
      clarified that the effects of adjacent radioactivity concentrations on FDG
      leakage were not marked. On the basis of investigations on partial volume effect
      and count rate performance, the following formulas were derived: For leakages of
      >or=28 mm Leakage radioactivity (MBq)=positron emission tomography (PET)
      radioactivity (MBq)x0.9. For leakages of >or=15 mm but <28 mm Leakage
      radioactivity (MBq)=PET radioactivity (MBq)x0.9x(0.0517xleakage size (mm)
      0.4029). In a volunteer study with 10 MBq leakage, SUV recalculated using the
      formula achieved 99.97% correction, whereas with 100 MBq leakage, SUV achieved
      67.5% resulting in poor correction. CONCLUSIONS: The present correction technique
      can accurately calculate SUV and could be useful for the clinical diagnosis of
      malignant tumors.

PMID- 18092140
TI  - Composite fibrin scaffolds increase mechanical strength and preserve
      contractility of tissue engineered blood vessels.
AB  - OBJECTIVES: We recently demonstrated that fibrin-based tissue engineered blood
      vessels (TEV) exhibited vascular reactivity, matrix remodeling and sufficient
      strength for implantation into the veins of an ovine animal model, where they
      remained patent for 15 weeks. Here we present an approach to improve the
      mechanical properties of fibrin-based TEV and examine the relationship between
      mechanical strength and smooth muscle cell (SMC) function. MATERIALS AND METHODS:
      To this end, we prepared TEV that were composed of two layers: a cellular layer
      containing SMC embedded in fibrin hydrogel to provide contractility and matrix
      remodeling; and a second cell-free fibrin layer composed of high concentration
      fibrinogen to provide mechanical strength. RESULTS: The ultimate tensile force of
      double-layered TEV increased with FBG concentration in the cell-free layer in a
      dose-dependent manner. Double-layered TEV exhibited burst pressure that was ten
      fold higher than single-layered tissues but vascular reactivity remained high
      even though the cells were constricting an additional tissue layer. CONCLUSION:
      These results showed that mechanical strength results largely from the
      biomaterial but contractility requires active cellular machinery. Consequently,
      they may suggest novel approaches for engineering biomaterials that satisfy the
      requirement for high mechanical strength while preserving SMC function.

PMID- 18092141
TI  - Probing DNA hybridization in homogeneous solution and at interfaces via
      measurement of the intrinsic fluorescence decay time of a single label.
AB  - The hybridization of DNA oligomers including molecular beacons can be detected by
      measurement of either the decay time or the intensity of a single fluorescent
      label attached to the end of the respective oligonucleotide. The method works
      both in solution and solid phase and can distinguish between fully complementary
      and mismatch sequences as demonstrated for a 15-mer oligonucleotide and a 25-mer
      molecular beacon. The fluorescence lifetime method is advantageous in (a)
      requiring a single label (and therefore a single labeling step) only; and (b),
      being based on measurement of a self-referenced magnitude that is hardly affected
      by parameters such as fluctuations in light intensity that make measurement of
      intensity more prone to interferences.

PMID- 18092142
TI  - Tubeless percutaneous neprolithotomy: the new gold standard.
AB  - PURPOSE: We present our experience with tubeless percutaneous nephrolithotomy
      (PCNL). PATIENTS AND METHODS: Between July 2004 and December 2006, 121 patients
      (82 males and 39 females) with 18-70 mm (mean 31.19 mm) renal stones underwent
      tubeless PCNL leaving only a 6 Fr externalized ureteric catheter. Their ages
      ranged between 4 and 80 years (mean 37.27). Two patients had bilateral disease,
      so a total of 123 renal units are included. The procedure was performed under
      general anesthesia in the prone (110 units) or supine position (13 units). A
      total of 133 punctures were performed. The punctures were single (114 units),
      double (8 units), or triple (1 unit). The approach was subcostal through the
      lower calyx (n=110) or middle calyx (n=10), or supracostal through the middle
      calyx (n=8) or upper calyx (n=5). RESULTS: Mean operative time was 46.30 min
      (range 15-100). Mean reduction in hemoglobin level was 1.57 g (range 0.3-4) with
      blood transfusion rate 4.13%. Complication rate was 9.9% in the form of perirenal
      collection (five patients), urinary leakage (two patients), fever (four
      patients), and hydrothorax (one patient). The ureteric catheter was left for 7-72
      h (mean 45.67). Postoperative analgesia was required in 22 patients (18.2%) with
      mean 22.9 mg diclofenac sodium per patient. Mean hospital stay was 50.69 h (range
      12-96) with 106 units (86.18%) rendered stone free, 13 (10.57%) with
      insignificant residuals, and four units (3.25%) were left with significant
      residual stones. CONCLUSIONS: Tubeless PCNL is a good option in non-complicated
      PCNL with the advantages of reduced hospital stay, low postoperative pain, and
      little need for postoperative analgesia.

PMID- 18092143
TI  - Long-term control or possible cure? Treatment of stage D2 prostate cancer under
      chemotherapy using cisplatin and estramustine phosphate followed by maximal
      androgen blockade.
AB  - Metastatic prostate cancer (PC) is incurable by androgen deprivation therapy
      alone, due to the presence of androgen-independent/supersensitive cells in
      hormone-naive PC. A 67-year-old man was diagnosed with PC (Gleason score, 5 + 4)
      with multiple bone metastases. He was treated by chemohormonal therapy with
      cisplatin and estramustine phosphate (EMP) followed by maximal androgen blockade,
      and showed a complete response. As of the time of writing, no clinical or
      prostate-specific antigen recurrence has been observed for over 15 years, despite
      cessation of the treatment. This is the first report to indicate a possible cure
      of metastatic PC by chemohormonal therapy combined with appropriate anti-tumor
      drugs targeted to both androgen-independent and -dependent clones before the
      hormone-refractory state.

PMID- 18092144
TI  - The role of CD4+CD25+ T regulatory cells in autoimmune diseases.
AB  - Among the several mechanisms that play role in maintaining peripheral self
      tolerance is the existence of a unique CD4+CD25+ population of naturally
      occurring regulatory T (Treg) cells that actively prevent both the activation and
      the effector function of autoreactive T cells that have escaped different
      mechanisms of tolerance. Many studies have shown the benefit of targeting this
      cell population by restoring self-tolerance. Therapies that could possibly
      increase the suppressive ability of T regulatory cells were proven to improve
      that course of autoimmune diseases.

PMID- 18092146
TI  - Fine mapping of a yield-enhancing QTL cluster associated with transgressive
      variation in an Oryza sativa x O. rufipogon cross.
AB  - A high-resolution physical map targeting a cluster of yield-related QTLs on the
      long arm of rice chromosome 9 has been constructed across a 37.4 kb region
      containing seven predicted genes. Using a series of BC3F4 nearly isogenic lines
      (NILs) derived from a cross between the Korean japonica cultivar Hwaseongbyeo and
      Oryza rufipogon (IRGC 105491), a total of seven QTLs for 1,000-grain weight,
      spikelets per panicle, grains per panicle, panicle length, spikelet density,
      heading date and plant height were identified in the cluster (P<or=0.0001). All
      seven QTLs were additive, and alleles from the low-yielding O. rufipogon parent
      were beneficial in the Hwaseongbyeo background. Yield trials with BC3F4 NILs
      showed that lines containing a homozygous O. rufipogon introgression in the
      target region out-yielded sibling NILs containing Hwaseongbyeo DNA by 14.2-17.7%,
      and out-yielded the Hwaseongbyeo parent by 16.2-23.7%. While higher yielding
      plants containing the O. rufipogon introgression were also taller and later than
      controls, the fact that all seven of the QTLs were co-localized in the same 37.4
      kb interval suggests the possibility that a single, pleiotropic gene acting as a
      major regulator of plant development may control this suite of agronomically
      important plant phenotypes.

PMID- 18092145
TI  - Apoptotic induction with bifunctional E.coli cytosine deaminase-uracil
      phosphoribosyltransferase mediated suicide gene therapy is synergized by curcumin
      treatment in vitro.
AB  - Development of novel suicide gene therapy vector with potential application in
      cancer treatment has a great impact on human health. Investigation to understand
      molecular mechanism of cell death is necessary to evaluate the therapeutic
      application of suicide vectors. For example, the bifunctional E.coli cytosine
      deaminase & uracil phosphoribosyltransferase fusion (CD-UPRT) gene expression is
      known to sensitize a wide range of cells toward nontoxic prodrug 5-flurocytosine
      (5-FC) by converting it to toxic compounds, but the exact pathway of cell death
      is yet to be defined. Herein, we investigated the mechanism of cell death by 5
      FC/CD-UPRT suicide system in both cancer and non-cancer cells and found that the
      optimum 5-FC concentration led to programmed cell death in vitro. The CD-UPRT
      expression of transfected cells was measured by the RT-PCR analysis. Biochemical
      assays, such as mitochondrial activity (MTS) and lactate dehydrogenase (LDH)
      measurements exhibited cell death. Microscopic experiments showed characteristic
      onset of apoptosis which was further supported by internucleosomal DNA cleavage
      of BrdU labeled cellular DNA, appearance of characteristic laddering of
      chromosomal DNA and involvement of caspase pathway. Furthermore, the 5-FC/CD-UPRT
      mediated apoptosis was potentiated with addition of a known anticancer agent
      curcumin. Our in vitro studies confirmed synergistic induction of apoptotic
      pathway in the combination treatment. Therefore, combination of 5-FC/CD-UPRT with
      curcumin could be a potential chemosensitization strategy for cancer treatment.

PMID- 18092147
TI  - Marker-assisted selection for early-season cold tolerance in sorghum: QTL
      validation across populations and environments.
AB  - Sorghum [Sorghum bicolor (L.) Moench] landraces from China generally exhibit
      excellent emergence and seedling vigor under cool conditions, and are being used
      as sources of genes for improvement of seedling cold tolerance in other
      cultivars. Marker-assisted selection (MAS) could expedite the introgression of
      genes from landraces into elite lines, however, only a few studies have
      empirically demonstrated efficacy of MAS for quantitatively inherited agronomic
      traits. In a preceding study we identified quantitative trait loci (QTL) for
      early-season performance in a recombinant inbred (RI) population, one parent of
      which was a cold-tolerant Chinese line, 'Shan Qui Red' (SQR). In this study,
      three SSR markers (Xtxp43, Xtxp51, and Xtxp211), each representing a QTL, were
      tested in two new populations: (Tx2794 x SQR F(3)) and (Wheatland x SQR
      BC(1)F(3)). Individual families were genotyped, and early-season field
      performance was measured for two years. Statistical analyses showed that the SQR
      allele of Xtxp43 had favorable effects on seedling vigor in both populations, and
      on emergence in the Tx2794 population. A large positive effect of the SQR allele
      of Xtxp51 was observed in the Tx2794 population for vigor and emergence. Slight
      genotype by environment interaction was observed for Xtxp51 in the Wheatland
      population. Marker Xtxp211 had small but significant effects on seedling vigor
      and emergence in both populations. Various interactions between loci were also
      significant. This study validated QTL markers in various genetic backgrounds, and
      demonstrated the utility of MAS for a quantitative trait, early-season cold
      tolerance, evaluated in the field.

PMID- 18092148
TI  - Pm37, a new broadly effective powdery mildew resistance gene from Triticum
      timopheevii.
AB  - Powdery mildew is an important foliar disease in wheat, especially in areas with
      a cool or maritime climate. A dominant powdery mildew resistance gene transferred
      to the hexaploid germplasm line NC99BGTAG11 from T. timopheevii subsp. armeniacum
      was mapped distally on the long arm of chromosome 7A. Differential reactions were
      observed between the resistance gene in NC99BGTAG11 and the alleles of the Pm1
      locus that is also located on chromosome arm 7AL. Observed segregation in F2:3
      lines from the cross NC99BGTAG11xAxminster (Pm1a) demonstrate that germplasm line
      NC99BGTAG11 carries a novel powdery mildew resistance gene, which is now
      designated as Pm37. This new gene is highly effective against all powdery mildew
      isolates tested so far. Analyses of the population with molecular markers
      indicate that Pm37 is located 16 cM proximal to the Pm1 complex. Simple sequence
      repeat (SSR) markers Xgwm332 and Xwmc790 were located 0.5 cM proximal and distal,
      respectively, to Pm37. In order to identify new markers in the region, wheat
      expressed sequence tags (ESTs) located in the distal 10% of 7AL that were
      orthologous to sequences from chromosome 6 of rice were targeted. The two new EST
      derived STS markers were located distal to Pm37 and one marker was closely linked
      to the Pm1a region. These new markers can be used in marker-assisted selection
      schemes to develop wheat cultivars with pyramids of powdery mildew resistance
      genes, including combinations of Pm37 in coupling linkage with alleles of the Pm1
      locus.

PMID- 18092149
TI  - Presence of functional cannabinoid receptors in human endocrine pancreas.
AB  - AIMS/HYPOTHESIS: We examined the presence of functional cannabinoid receptors 1
      and 2 (CB1, CB2) in isolated human islets, phenotyped the cells producing
      cannabinoid receptors and analysed the actions of selective cannabinoid receptor
      agonists on insulin, glucagon and somatostatin secretion in vitro. We also
      described the localisation on islet cells of: (1) the endocannabinoid-producing
      enzymes N-acyl-phosphatidyl ethanolamine-hydrolysing phospholipase D and
      diacylglycerol lipase; and (2) the endocannabinoid-degrading enzymes fatty acid
      amidohydrolase and monoacyl glycerol lipase. METHODS: Real-time PCR, western
      blotting and immunocytochemistry were used to analyse the presence of
      endocannabinoid-related proteins and genes. Static secretion experiments were
      used to examine the effects of activating CB1 or CB2 on insulin, glucagon and
      somatostatin secretion and to measure changes in 2-arachidonoylglycerol (2-AG)
      levels within islets. Analyses were performed in isolated human islets and in
      paraffin-embedded sections of human pancreas. RESULTS: Human islets of Langerhans
      expressed CB1 and CB2 (also known as CNR1 and CNR2) mRNA and CB1 and CB2
      proteins, and also the machinery involved in synthesis and degradation of 2-AG
      (the most abundant endocannabinoid, levels of which were modulated by glucose).
      Immunofluorescence revealed that CB1 was densely located in glucagon-secreting
      alpha cells and less so in insulin-secreting beta cells. CB2 was densely present
      in somatostatin-secreting delta cells, but absent in alpha and beta cells. In
      vitro experiments revealed that CB1 stimulation enhanced insulin and glucagon
      secretion, while CB2 agonism lowered glucose-dependent insulin secretion, showing
      these cannabinoid receptors to be functional. CONCLUSIONS/INTERPRETATION:
      Together, these results suggest a role for endogenous endocannabinoid signalling
      in regulation of endocrine secretion in the human pancreas.

PMID- 18092150
TI  - Terlipressin as a rescue therapy for catecholamine-resistant septic shock in
      children.
AB  - OBJECTIVE: To evaluate the effect of terlipressin on oxygenation, PaO2/FIO2,
      heart rate, mean arterial pressure, and mortality in children with septic shock
      refractory to high doses of dopamine/dobutamine and adrenaline. DESIGN AND
      SETTING: A randomized, nonblind study in the pediatric intensive care unit of a
      university hospital. PATIENTS AND MEASUREMENTS: We studied 58 children with
      septic shock and refractory hypotension despite fluid loading and high doses of
      catecholamines, randomly enrolled to terlipressin (TP, n=30) or control (n=28).
      TP was administered as intravenous bolus doses of 20 microg/kg every 6 h for a
      maximum of 96 h. Hemodynamic changes, PaO2/FIO2 rates, length of stay, and
      mortality rate in PICU were recorded prospectively. RESULTS: Mean arterial
      pressure and PaO2/FIO2 significantly increased, and heart rate significantly
      decreased 30 min after each TP treatment, but mortality did not differ from
      control (67.3% vs. 71.4%). Mean stay in the PICU was shorter in the TP group
      (13.4+/-7.9 vs. 20.2+/-9.7 days and was longer among nonsurvivors of the TP group
      vs. control (10.4+/-6.9 vs. 6.2+/-3.4 days). Blood urea nitrogen, creatinine,
      AST, ALT, and urine output of patients in the TP group did not change after
      terlipressin. CONCLUSIONS: Although terlipressin infusion had no effect on
      mortality, it significantly increases mean arterial pressure, PaO2/FIO2, and
      survival time in nonsurvivors. Terlipressin seems to cause no adverse effect but
      warrants further evaluation as a rescue therapy in refractory septic shock.

PMID- 18092151
TI  - Duration of adrenal inhibition following a single dose of etomidate in critically
      ill patients.
AB  - OBJECTIVE: To determine the incidence and duration of adrenal inhibition induced
      by a single dose of etomidate in critically ill patients. DESIGN: Prospective,
      observational cohort study. SETTING: Three intensive care units in a university
      hospital. PATIENTS: Forty critically ill patients without sepsis who received a
      single dose of etomidate for facilitating endotracheal intubation. MEASUREMENTS
      AND MAIN RESULTS: Serial serum cortisol and 11beta-deoxycortisol samples were
      taken at baseline and 60 min after corticotropin stimulation test (250 microg 1
      24 ACTH) at 12, 24, 48, and 72 h after etomidate administration. Etomidate
      related adrenal inhibition was defined by the combination of a rise in cortisol
      less than 250 nmol/l (9 microg/dl) after ACTH stimulation and an excessive
      accumulation of serum 11beta-deoxycortisol concentrations at baseline. At 12 h
      after etomidate administration, 32/40 (80%) patients fulfilled the diagnosis
      criteria for etomidate-related adrenal insufficiency. This incidence was
      significantly lower at 48 h (9%) and 72 h (7%). The cortisol to 11beta
      deoxycortisol ratio (F/S ratio), reflecting the intensity of the 11beta
      hydroxylase enzyme blockade, improved significantly over time. CONCLUSIONS: A
      single bolus infusion of etomidate resulted in wide adrenal inhibition in
      critically ill patients. However, this alteration was reversible by 48 h
      following the drug administration. The empirical use of steroid supplementation
      for 48 h following a single dose of etomidate in ICU patients without septic
      shock should thus be considered. Concomitant serum cortisol and 11beta
      deoxycortisol dosages are needed to provide evidence for adrenal insufficiency
      induced by etomidate in critically ill patients.

PMID- 18092152
TI  - Inhibition by oxytocin of methamphetamine-induced hyperactivity related to
      dopamine turnover in the mesolimbic region in mice.
AB  - Accumulated data have shown the neuroactive properties of oxytocin (OT), a
      neurohypophyseal neuropeptide, and its capability of reducing the abuse potential
      of drugs. The present study investigated the effect of OT on methamphetamine
      (MAP)-induced hyperactivity in mice and its possible mechanism of action.
      Locomotor activity was measured after administered with MAP using an infrared
      sensor. High-performance liquid chromatography with electrochemical detection
      (HPLC-ECD) was used to detect the content of monoamines and their metabolites in
      the striatum and accumbens and prefrontal cortex in mice after the behavioral
      test. OT (0.1, 0.5, and 2.5 microg/mouse, i.c.v.) had no effect on locomotor
      activity in naive mice, but inhibited, in a dose-dependent manner, the
      hyperactivity induced by acute administration of MAP. Atosiban (Ato) (2.0
      microg/mouse, i.c.v.), the selective inhibitor of OT receptor, attenuated the
      inhibitory effect of OT on MAP. A marked reduction of the ratios of 3, 4
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) to dopamine (DA)
      was observed in the striatum and accumbens of mice after acute administration of
      MAP. OT (2.5 microg, i.c.v.) significantly inhibited the reduction of DOPAC/DA
      and HVA/DA ratios. However, Ato decreased the ratio of DOPAC/DA significantly in
      mice compared with OT (2.5 microg) in combination with MAP. There was no
      significant change in serotonin (5-HT) metabolism in mice after a single
      administration of MAP. These results suggested that OT inhibited the MAP-induced
      hyperactivity by altering the DA turnover in the mesolimbic region of mice.

PMID- 18092153
TI  - Vasodilator effects of adenosine on retinal arterioles in streptozotocin-induced
      diabetic rats.
AB  - Adenosine is a potent vasodilator of retinal blood vessels and is implicated to
      be a major regulator of retinal blood flow during metabolic stress, but little is
      known about the impact of diabetes on the role of adenosine in regulation of
      retinal hemodynamics. Therefore, we examined how diabetes affects adenosine
      induced vasodilation of retinal arterioles. Male Wistar rats were treated with
      streptozotocin (80 mg/kg, intraperitoneally), and experiments were performed 6-8
      weeks later. Rats were treated with tetrodotoxin (50 microg/kg, intravenously
      [i.v.]) to eliminate any nerve activity and prevent movement of the eye and
      infused with methoxamine continuously to maintain adequate systemic circulation.
      Fundus images were captured with a digital camera that was equipped with a
      special objective lens, and diameters of retinal arterioles were measured.
      Adenosine increased diameters of retinal arterioles and decreased systemic blood
      pressure. These responses were significantly attenuated by the nitric oxide
      synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg, i.v.) and the
      adenosine triphosphate-dependent K+ (K(ATP)) channel blocker glibenclamide (20
      mg/kg, i.v.). The depressor responses to adenosine were reduced in diabetic rats,
      whereas diabetes did not alter vasodilation of retinal arterioles to adenosine.
      In contrast, both depressor response and vasodilation of retinal arteriole to
      acetylcholine were reduced in diabetic rats. The retinal vasodilator responses to
      adenosine and acetylcholine observed in diabetic rats were diminished by N(G)
      nitro-L-arginine methyl ester. There were no differences in the responses to
      pinacidil, a K(ATP) channel opener, between the diabetic and nondiabetic rats.
      These results suggest that both the activation of nitric oxide synthase and
      opening of K(ATP) channels contribute to the vasodilator effects of adenosine in
      rats in vivo. However, diabetes has no significant impact on the vasodilation
      mediated by these mechanisms in the retinal circulation.

PMID- 18092154
TI  - Electrophysiological profile of propiverine--relationship to cardiac risk.
AB  - Drugs that prolong the QT interval by blocking human ether-a-go-go (HERG)
      channels may enhance the risk of ventricular arrhythmia. The spasmolytic drug
      propiverine is widely used for the therapy of overactive bladder (OAB). Here, we
      have investigated the effects of propiverine on cardiac ion channels and action
      potentials as well as on contractile properties of cardiac tissue, in order to
      estimate its cardiac safety profile, because other drugs used in this indication
      had to be withdrawn due to safety reasons. Whole-cell patch clamp technique was
      used to record the following cardiac ion currents: rapidly and slowly activating
      delayed rectifier K+ current (I(Kr), I(Ks)), ultra rapidly activating delayed
      rectifier K+ current (I(Kur)), inwardly rectifying K+ current I(K1), transient
      outward K+ current (I(to)), and L-type Ca2+ current (I(Ca,L)). Action potentials
      in cardiac tissue biopsies were recorded with conventional microelectrodes. The
      torsade de pointes screening assay (TDPScreen) was used for drug scoring.
      Propiverine blocked in a concentration-dependent manner HERG channels expressed
      in HEK293 cells, as well as native I(Kr) current in ventricular myocytes of
      guinea pig (IC50 values: 10 microM and 1.8 microM respectively). At high
      concentrations (100 microM), propiverine suppressed I(Ks). I(K1) and the
      transient outward current I(to) and I(Kur) were not affected. In guinea-pig
      ventricular and human atrial myocytes, propiverine also blocked I(Ca,L) (IC50
      values: 34.7 microM and 41.7 microM, respectively) and reduced force of
      contraction. Despite block of I(Kr), action potential duration was not prolonged
      in guinea-pig and human ventricular tissue, but decreased progressively until
      excitation failed altogether. Similar effects were observed in dog Purkinje
      fibers. Propiverine obtained a low score in the TDPScreen. In conclusion, in
      vitro and in vivo studies of propiverine do not provide evidence for an enhanced
      cardiovascular safety risk. We propose that lack of torsadogenic risk of
      propiverine is related to enhancement of repolarization reserve by block of
      I(Ca,L).

PMID- 18092155
TI  - Disease progression, drug action and Parkinson's disease: why time cannot be
      ignored.

PMID- 18092156
TI  - A probabilistic meta-predictor for the MHC class II binding peptides.
AB  - Several computational methods for the prediction of major histocompatibility
      complex (MHC) class II binding peptides embodying different strengths and
      weaknesses have been developed. To provide reliable prediction, it is important
      to design a system that enables the integration of outcomes from various
      predictors. The construction of a meta-predictor of this type based on a
      probabilistic approach is introduced in this paper. The design permits the easy
      incorporation of results obtained from any number of individual predictors. It is
      demonstrated that this integrated method outperforms six state-of-the-art
      individual predictors based on computational studies using MHC class II peptides
      from 13 HLA alleles and three mouse MHC alleles obtained from the Immune Epitope
      Database and Analysis Resource. It is concluded that this integrative approach
      provides a clearly enhanced reliability of prediction. Moreover, this
      computational framework can be directly extended to MHC class I binding
      predictions.

PMID- 18092158
TI  - Antimicrobial activity of an endophytic Xylaria sp.YX-28 and identification of
      its antimicrobial compound 7-amino-4-methylcoumarin.
AB  - An endophytic Xylaria sp., having broad antimicrobial activity, was isolated and
      characterized from Ginkgo biloba L. From the culture extracts of this fungus, a
      bioactive compound P3 was isolated by bioactivity-guided fractionation and
      identified as 7-amino-4-methylcoumarin by nuclear magnetic resonance, infrared,
      and mass spectrometry spectral data. The compound showed strong antibacterial and
      antifungal activities in vitro against Staphylococcus aureus [minimal inhibitory
      concentrations (MIC) 16 microg.ml(-1)], Escherichia coli (MIC, 10 microg.ml(-1)),
      Salmonella typhia (MIC, 20 microg.ml(-1)), Salmonella typhimurium (MIC, 15
      microg.ml(-1)), Salmonella enteritidis (MIC, 8.5 microg.ml(-1)), Aeromonas
      hydrophila (MIC, 4 microg.ml(-1)), Yersinia sp. (MIC, 12.5 microg.ml(-1)), Vibrio
      anguillarum (MIC, 25 microg.ml(-1)), Shigella sp. (MIC, 6.3 microg.ml(-1)),
      Vibrio parahaemolyticus (MIC, 12.5 microg.ml(-1)), Candida albicans (MIC, 15
      microg.ml(-1)), Penicillium expansum (MIC, 40 microg.ml(-1)), and Aspergillus
      niger (MIC, 25 microg.ml(-1)). This is the first report of 7-amino-4
      methylcoumarin in fungus and of the antimicrobial activity of this metabolite.
      The obtained results provide promising baseline information for the potential use
      of this unusual endophytic fungus and its components in the control of food
      spoilage and food-borne diseases.

PMID- 18092157
TI  - Immune-related genes associated with intestinal tissue in the sea cucumber
      Holothuria glaberrima.
AB  - We have analyzed 5,173 expressed sequence tags (ESTs) from three cDNA libraries
      of normal and regenerating intestinal tissue of the sea cucumber Holothuria
      glaberrima and found 22 putative immune-related genes. These sequences showed
      similarities (e-value approx 10(-8)) to genes involved in immune processes or
      expressed by immune cells. Sequences were analyzed using bioinformatic tools to
      determine a putative identity. In addition, phylogenetic analyses were performed
      to find relationships with similar proteins in other organisms. The mRNAs for ten
      sequences were detected in coelomocytes by using reverse transcription-polymerase
      chain reaction (RT-PCR). Moreover, five of them showed a significant increase in
      expression after an LPS challenge, while the other five showed no significant
      changes. These results show the variety of immune molecules that may be found in
      holothurians and support the idea that the invertebrate immune system is more
      than a collection of simple innate responses. Our study also provides new data of
      importance in deciphering the evolution and development of the immune system.

PMID- 18092159
TI  - Optimal 3-T MRI for depiction of the finger A2 pulley: comparison between T1
      weighted, fat-saturated T2-weighted and gadolinium-enhanced fat-saturated T1
      weighted sequences.
AB  - OBJECTIVE: To compare three spin-echo sequences, transverse T1-weighted (T1WI),
      transverse fat-saturated (FS) T2-weighted (T2WI), and transverse gadolinium
      enhanced (Gd) FS T1WI, for the visualisation of normal and abnormal finger A2
      pulley with magnetic resonance (MR) imaging at 3 tesla (T). MATERIALS AND
      METHODS: Sixty-three fingers from 21 patients were consecutively investigated.
      Two musculoskeletal radiologists retrospectively compared all sequences to assess
      the visibility of normal and abnormal A2 pulleys and the presence of motion or
      ghost artefacts. RESULTS: Normal and abnormal A2 pulleys were visible in 94%
      (59/63) and 95% (60/63) on T1WI sequences, in 63% (40/63) and 60% (38/63) on FS
      T2WI sequences, and in 87% (55/63) and 73% (46/63) on Gd FS T1WI sequences when
      read by the first and second observer, respectively. Motion and ghost artefacts
      were higher on FS T2WI sequences. Seven among eight abnormal A2 pulleys were
      detected, and were best depicted with Gd FS T1WI sequences in 71% (5/7) and 86%
      (6/7) by the first and the second observer, respectively. CONCLUSION: In 3-T MRI,
      the comparison between transverse T1WI, FS T2WI, and Gd FS T1WI sequences shows
      that transverse T1WI allows excellent depiction of the A2 pulley, that FS T2WI
      suffers from a higher rate of motion and ghost artefacts, and transverse Gd FS
      T1WI is the best sequence for the depiction of abnormal A2 pulley.

PMID- 18092160
TI  - Magnetic resonance imaging of surgically confirmed anterior cruciate ligament
      graft disruption.
AB  - OBJECTIVE: To evaluate previously described primary and secondary MRI signs of
      disruption to anterior cruciate ligament (ACL) grafts in surgically proven cases.
      MATERIALS AND METHODS: We retrospectively analyzed MR images of 48 patients (mean
      age 29 years) with clinically suspected ACL graft disruption. All patients had
      surgical confirmation of the MRI findings. The reviewers analyzed the cases
      blinded to the surgical results and assessed each of the primary and secondary
      MRI signs of graft disruption individually. Subsequently, a final impression of
      the graft integrity based on a comprehensive assessment of all of the primary and
      secondary findings was made. RESULTS: Utilizing a comprehensive assessment of
      previously described primary and secondary MR findings of ACL graft disruption,
      the blinded reviewers were able to identify correctly full-thickness graft tears
      with test accuracy of 85%, sensitivity of 72%, and specificity of 100%.
      Individual assessment of the primary finding of graft fiber discontinuity had
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of 72%, 100%, 100%, 77% and 85%, respectively, for full-thickness
      tears. Other individual primary and secondary findings were less reliable;
      however, the primary findings of marked segmental thinning of the graft and
      markedly abnormal graft orientation, and the secondary findings of bone
      contusions in the lateral compartment and large joint effusion, had high
      specificity and positive predictive value. Of the four missed cases, two had
      associated arthrofibrosis. CONCLUSION: The comprehensive assessment of previously
      described primary and secondary MRI findings of ACL graft disruption has high
      test specificity and moderately high test accuracy. The presence of graft fiber
      discontinuity is the most reliable primary or secondary finding when assessed
      individually. Marked segmental thinning of the graft and abnormal fiber
      orientation, and the presence of bone contusions in the lateral compartment and
      large joint effusion, are less reliable overall but are highly suggestive of full
      thickness graft tear when present.

PMID- 18092161
TI  - Lengthening of short bones by distraction osteogenesis--results and
      complications.
AB  - We performed bone lengthening surgery on 12 metacarpals and 14 metatarsals of 15
      patients. The mean age for metacarpal and metatarsal lengthening was 14.5 (10-21)
      and 17.5 (10-25) years, respectively. We used a unilateral or a circular external
      fixator. The mean healing index of the metacarpals and metatarsals was 1.6 (1.1
      2.3) and 1.6 (1.0-2.0) months/cm, respectively. The mean increase in metacarpal
      and metatarsal length was 17.6 (13-26) and 24.3 (20-30) mm, respectively. The
      functional scores of the metatarso-phalangial (MTP) joint of lengthened
      metatarsals for the lesser toe were excellent in 12 and good in two cases based
      on the American Orthopaedic Foot and Ankle Society (AOFAS) scoring system.
      Complications were seen in six of the metatarsal lengthening cases including four
      angulations, one subluxation and one non-union. We conclude that the periosteum
      must be protected with percutaneous osteotomy and lengthening should be performed
      at a rate of 0.25 mm twice a day and should not exceed 40% of the original bone
      length (or >20 mm).

PMID- 18092162
TI  - Humeral head resurfacing for fixed anterior glenohumeral dislocation.
AB  - The purpose of this prospective study was to describe cementless humeral surface
      replacement arthroplasty (CHSRA) as a bone preserving treatment option for
      patients with fixed anterior glenohumeral dislocation. Ten patients with post
      traumatic fixed anterior glenohumeral dislocation underwent CHSRA with a mean
      follow-up of 24 months. All patients were evaluated clinically using the Constant
      score and with radiographs in two planes. There were two reoperations: one
      patient developed glenoid erosion and was revised and in another case
      redislocation occurred. Clinical or radiographical signs of implant loosening
      were not found. The humeral head centred in the glenoid in nine out of ten cases
      radiographically. The Constant score increased from 20 points preoperatively to
      61 points postoperatively (p < 0.007). CHSRA is a viable treatment option for
      elderly patients with fixed anterior glenohumeral dislocation and bone defects of
      the humeral head. Good clinical results and a moderate complication rate were
      found in the short term.

PMID- 18092163
TI  - Acute renal failure due to hypercalcemia-related nephrocalcinosis in a patient of
      non-Hodgkin's lymphoma featuring swelling of bilateral kidneys.

PMID- 18092164
TI  - False positive PET scanning caused by inactivated influenza virus vaccination
      during complete remission from anaplastic T-cell lymphoma.

PMID- 18092165
TI  - Cutaneous vasculitis as an initiating paraneoplastic symptom in Hodgkin lymphoma.
AB  - Skin vasculitis may be associated with infections and autoimmune diseases.
      Furthermore, vasculitis may appear as a paraneoplastic symptom. A 19-year-old
      male patient was examined with swollen joints and papules presented on lower
      extremitis. Laboratory results showed high erythrocyte sedimentation ratio,
      positive C reactive protein, increased number of leukocytes and high circulating
      immune complex level. Histopatology of skin biopsy specimen proved vasculitis.
      ANCA was not present. No other changes could be observed besides skin
      involvement. Symptoms disappeared on 0.5-mg/bwkg methylprednisolon therapy. Few
      weeks later, enlarged cervical lymph nodes developed besides fever and weight
      loss. Biopsy indicated the presence of mixed cell type Hodgkin lymphoma.
      Appropriate examinations revealed clinical stage III/B with favorable prognosis
      (IPS=2). After eight cycles of ABVD therapy complete remission was achieved as
      confirmed by FDG-PET. As a consequence of the treatment of Hodgkin lymphoma,
      vasculitis also disappeared. The present case report calls to attention the
      importance of careful examinations to exclude other diseases, especially
      malignancies that may remain at the background of cutaneous vasculitis. Treatment
      of the primary disease also results in the improvement of secondary skin
      vasculitis.

PMID- 18092166
TI  - N-terminal pro-BNP in sclerodermic patients on bosentan therapy for PAH.
AB  - Systemic sclerosis (SSc) is characterized by vascular dysfunction that may lead
      to pulmonary artery hypertension (PAH). The N-terminal pro-B type natriuretic
      peptide (NT-proNBP), a marker of cardiac failure, is a diagnostic marker of early
      PAH in patients with SSc without heart failure. Our aim was to determine whether
      NT-proBNP levels may be a useful tool to evaluate the response to bosentan
      therapy in patients with PAH secondary to SSc. Ten patients with symptomatic,
      severe PAH secondary to SSc, received bosentan, 62.5 mg twice a day for 4 weeks
      followed by 125 mg twice a day for 7 months. Ten patients with SSc without PAH
      served as controls for basal level of NT-proBNP. Blood samples were obtained
      before the beginning of the therapy and after 3 and 7 months of treatment. SSc
      patients with PAH had significantly higher serum levels of NT-proBNP than those
      without PAH, at baseline. After 3 and 7 months of therapy, NT-proBNP
      concentration showed a progressive decrease, nearly approaching statistical
      difference at 7 months when compared to baseline levels (P=0.953 and P=0.600).
      Our results show that serum NT-proBNP levels may be a useful marker for the
      response to bosentan therapy in patients with PAH secondary to SSc.

PMID- 18092167
TI  - TREX1 polymorphisms associated with autoantibodies in patients with systemic
      lupus erythematosus.
AB  - Three-prime repair exonucleases 1 and 2 (TREX1 and TREX2) play a role in the
      metabolism and clearance of DNA. The objective of this study was to confirm
      whether polymorphisms of TREX1 and TREX2 are associated with genetic
      susceptibility to systemic lupus erythematosus (SLE), and examine associations
      with autoantibodies (auto-Abs) in SLE. We investigated the genetic variants in 24
      Korean individuals by direct sequencing. The genotype distributions of single
      nucleotide polymorphisms (SNPs) and haplotypes were analyzed with multiple
      logistic regression models while controlling for covariates. We identified 12 and
      5 SNPs of TREX1 and TREX2, of which -20260G>C, -389T>C, -381C>T, and +531C>T SNPs
      of TREX1; -23386G>C, -14703G>A, -7279C>T, and +1747C>T SNPs of TREX2; and each of
      three haplotypes were selected for larger scale genotyping (n = 1,053). No
      statistically significant association with the risk of SLE was observed in TREX1
      and TREX2. TREX1 polymorphism -20260G>C showed protective effect on the
      production of anti-Ro Ab, and +531C>T in exon 16 and ht2 [G-T-C-T] showed also
      protective effect on the production of anti-dsDNA Ab, although the effect of
      +531C>T disappeared after multiple correction.

PMID- 18092168
TI  - Chromosome 5 inversion in two siblings, one with Klinefelter syndrome and
      systemic sclerosis, the other with rheumatoid arthritis.

PMID- 18092169
TI  - Translation and validation of Moroccan Western Ontario and McMaster Universities
      (WOMAC) osteoarthritis index in knee osteoarthritis.
AB  - The aim of this study is to assess the reliability and validity of the Western
      Ontario and McMaster University Osteoarthritis Index (WOMAC) in Moroccan patients
      with knee osteoarthritis. The WOMAC was translated and back translated to and
      from dialectal Arabic, pre-tested and reviewed by a committee following the
      Guillemin criteria. The Moroccan version of the WOMAC was administered twice
      during a 24-48 h interval to 71 Moroccan patients with symptomatic knee
      osteoarthritis, fulfilling the revised criteria of the American College of
      Rheumatology. The test-retest reliability was assessed using intra-class
      correlation coefficient, and the Bland and Altman method. Internal consistency
      was assessed by Cronbach's alpha coefficient. Construct validity was tested by
      correlating the WOMAC subscales with visual analogic scale (VAS) of pain, VAS of
      handicap, maximum distance walked and clinical characteristics. The Moroccan
      version of the WOMAC showed good reliability, with ICC values of the three
      dimensions: pain, stiffness and physical function being 0.80, 0.77 and 0.89,
      respectively. Bland and Altman analysis showed that means of differences did not
      differ significantly from 0 and that no systematic trend was observed. Internal
      consistency with Cronbach's alpha for pain was found to be 0.76, and its
      equivalents for stiffness and physical function subscales were evaluated at 0.76,
      0.90, respectively. Construct validity showed statistically significant
      correlation with all WOMAC subscales and VAS of pain (rho=0.38, 0.42, 0.63
      respectively, P<0.01). Correlation between VAS handicap (rho=0.38 P<0.001) and
      maximum distance walked (rho=-0.40, P<0.01) was observed with physical function
      subscale. There was no correlation between age, duration of disease, BMI and
      severity of pain and physical function in knee OA. The Moroccan version of the
      WOMAC is a comprehensible, reliable, and valid instrument to measure outcome in
      patients with knee OA.

PMID- 18092170
TI  - Noninvasive assessment of impaired endothelial dysfunction in mucocutaneous
      Behcet's disease.
AB  - Noninvasive assessment of endothelial dysfunction (ED) and diagnosing the early
      vascular development of atherosclerosis in active mucocutaneous Behcet's disease.
      Twenty-nine active BD patients (study group) without any obstructive vascular
      involvement were compared with twenty-nine healthy controls (control group) in
      terms of ED utilizing endothelium-dependent dilation as well as endothelium
      independent dilation (FMD), which was assessed by measuring changes in brachial
      artery diameter following sublingual glyceril trinitrate (400 microg Nitrolingual
      spray). All patients underwent a complete transthoracic echocardiographic and
      tissue Doppler study. A standard form was utilized for the documentation of the
      presence or absence of the known risk factors for atherosclerotic vascular
      disease. Statistical analysis was performed by utilizing SPSS version 11. There
      was no difference between patients and controls in terms of echocardiographic and
      tissue Doppler parameters as well as baseline brachial artery diameters. Flow
      mediated dilation showed 38% impairment in study group compared with control
      (P<0.05). Endothelium-independent NTG dilatation did not differ in both groups.
      Ultrasonography is an easily applicable noninvasive method for following BD
      patients for the risk of ED, which may preclude to atherosclerosis, save time and
      cost-effective.

PMID- 18092171
TI  - Considerations on the use of diagnostic markers in management of patients with
      bladder cancer.
AB  - Although the incidence of bladder cancer lags behind that of other malignancies,
      it has the highest rate of recurrence among all US malignancies. The propensity
      to recur and the possibility of disease progression require aggressive
      surveillance, which has led to bladder cancer being the most expensive malignancy
      to treat in the United States. Current non-tailored surveillance strategies
      applied uniformly to all patients with non-muscle invasive bladder cancer may
      impose excessive diagnostic burden on patients with low-grade disease for the
      sake of adequately monitoring those with potentially aggressive disease. The
      recent identification of several bladder cancer tumor markers has led to attempts
      to determine if these markers can enhance existing surveillance strategies by
      possibly tailoring surveillance strategies to individual patients. These markers
      may result in cost savings by properly identifying which patients can safely
      delay cystoscopy and which patients require more periodic assessment.
      Furthermore, we may be able to identify those patients with "occult disease" that
      require more invasive assessments and earlier aggressive treatment. We will
      review diagnostic considerations in the use of these markers for the detection of
      recurrent bladder cancer and summarize the benefits and costs of the more
      promising bladder cancer markers.

PMID- 18092172
TI  - Rare anterior shoulder dislocation in a toddler.
AB  - Traumatic anterior shoulder dislocation in toddlers and pediatric patients is a
      very rare injury pattern. The treatment and the recurrence rate are mostly
      extrapolated from adult and adolescent data. A 2-year-old toddler is presented
      with a first-time traumatic shoulder dislocation caused by a pull on the abducted
      arm. The treatment included a gentle closed reduction performing the Milch
      maneuver and a short-sling immobilization. The 2.5-year-follow-up demonstrated a
      stable shoulder with free range of motion while still having a Hill-Sachs-lesion.
      Shoulder dislocation in toddlers maybe addressed less aggressively after closed
      reduction than in adults due to an unknown recurrence rate.

PMID- 18092173
TI  - How many sentinel nodes should be harvested in oral squamous cell carcinoma?
AB  - The number of harvested lymph nodes when performing sentinel lymph node (SLN)
      biopsy remains controversial. The aim of this study was to examine the maximum
      number of nodes to be harvested for histopathological analysis. We also wanted to
      determine if the level of radioactivity within a SLN or its size were indicators
      for the likelihood of nodal metastases. The SLNs from 34 neck dissection
      specimens from patients with T1/T2 N0 oral and oropharyngeal carcinomas were
      included. Altogether 76 SLNs were measured for radioactivity and lymph node
      dimensions and volume. Tumour was identified in 16 of 76 nodes (positive nodes),
      and the remaining 60 nodes were free from tumour (negative nodes). In 9 of 16
      cases, metastases were in the hottest node. Two patients had more than one
      positive SLN: the first and fourth hottest in one and the second and fourth
      hottest nodes in another contained tumour. However, all patients would have been
      staged accurately if only the hottest three sentinel nodes had been retrieved.
      Lymph nodes that contained tumour had a greater maximum diameter than non
      metastatic SLNs. To stage the neck accurately, only the three hottest lymph nodes
      required sampling.

PMID- 18092174
TI  - Prevalence of skin and back diseases in geriatric care nurses.
AB  - OBJECTIVES: The prevalence of hand eczema, low back disorders (LBD) and
      neck/shoulder disorders (NSD) in geriatric nurses and the association of work
      related factors with hand eczema, LBD and NSD in geriatric nurses were examined.
      METHODS: The cross-sectional study comprises 1,390 nurses and nursing aides.
      Nurses underwent clinical examinations of their hands and their back and answered
      a questionnaire. Odds ratios (ORs) and 95% confidence intervals (95% CI) for
      putative risk factors were calculated by logistic regression. RESULTS: The point
      prevalence of hand eczema was 18.0%. Disposing factors, like atopic eczema in
      childhood and dry or itching body skin, were statistically significant risk
      factors for irritant skin changes. Hand cleaning and hand care were not
      predictive for hand eczema. LBD was observed in 47.9% and NSD in 16.6% of the
      nurses. Increasing age and years in the nursing profession, prior treatment of
      back disorder and psychological stress were significant risk factors for LBD and
      NSD. CONCLUSIONS: Hand eczema and LBD or NSD are often found in geriatric nurses.
      Therefore, workplace-related health promotion should be improved for geriatric
      nurses.

PMID- 18092175
TI  - Physiological responses at five estimates of critical velocity.
AB  - The purpose of this study was to compare critical velocity (CV) estimates from
      five mathematical models, and to examine the oxygen uptake (VO(2)) and heart rate
      (HR) responses during treadmill runs at the five estimates of CV. Ten subjects
      (six males and four females) performed one incremental test to determine maximal
      oxygen consumption (VO(2max)) and four or five randomly ordered constant-velocity
      trials on a treadmill for the estimation of CV. Five mathematical models were
      used to estimate CV for each subject including two linear, two nonlinear, and an
      exponential model. Up to five randomly ordered runs to exhaustion were performed
      by each subject at treadmill velocities that corresponded to the five CV
      estimates, and VO(2) and HR responses were monitored throughout each trial. The 3
      parameter, nonlinear (Non-3) model produced CV estimates that were significantly
      (P < 0.05) less than the other four models. During runs at CV estimates, five
      subjects did not complete 60 min at the their estimate from the Non-3 model, nine
      did not complete 60 min at their estimate from the Non-2 model, and no subjects
      completed 60 min at any estimate from the other three models. The mean HR value
      (179 +/- 18 beats min(-1), HR(peak)) at the end of runs at CV using the Non-3
      model was significantly less than the maximal HR (195 +/- 7 beats min(-1),
      HR(max)) achieved during the incremental trial to exhaustion. However, mean
      HR(peak) values from runs at all other CV estimates were not significantly
      different from HR(max). Furthermore, data indicated that mean HR(peak) values
      increased during runs at CV estimates from the third minute to the end of
      exercise for all models, and that these increases in VO(2) (range = 367-458 ml
      min(-1)) were significantly greater than that typically associated with O(2)
      drift ( approximately 200 ml min(-1)) for all but the exponential model,
      indicating a VO(2) slow component associated with CV estimates from four of the
      five models. However, the mean VO(2) values at the end of exercise during the
      runs at CV estimates for all five mathematical models were significantly less
      than the mean VO(2max) value. These results suggest that, in most cases, CV
      estimated from the five models does not represent a fatigueless task. In
      addition, the mean CV estimates from the five models varied by 18%, and four of
      the five mean CV estimates were within the heavy exercise domain. Therefore, CV
      would not represent the demarcation point between heavy and severe exercise
      domains.

PMID- 18092176
TI  - Anemia and iron status in young fertile non-professional female athletes.
AB  - We evaluated the effects of regular physical exercise on anemia and iron status
      in young non-professional female athletes. A total of 191 healthy white Italian
      women (23.5 +/- 4.68 years) were analyzed; 70 were non-professional athletes
      performing 11.1 +/- 2.63 h week(-1) exercise and 121 were sedentary controls.
      Blood markers of anemia and iron status-hemoglobin (Hb), hematocrit (Hct), red
      blood cells (RBC), serum ferritin, iron, transferrin (Tf), transferrin saturation
      (TfS), soluble transferrin receptor (sTfR), and the sTfR/log ferritin ratio (sTfR
      F index)-were evaluated. Anemia threshold was Hb < 120 g l(-1). Ferritin
      concentrations < 12 microg l(-1) were considered as iron deficiency (ID).
      Frequency of anemia (15.7 versus 10.7%, P = 0.32), ID (27.1 versus 29.8%, P =
      0.70), and ID anemia (8.6 versus 5.8%, P = 0.46) was not different in athletes
      and controls. However, athletes were threefold more likely than controls (17.1
      versus 5.8%) to have serum iron < 50 microg dl(-1) [odds ratio (OR) 3.37, P =
      0.012]. Low-TfS (<15%) was found in 25.7% of athletes and in 13.2% of controls,
      OR 2.27, P = 0.030. Elevated-sTfR (>1.76 mg l(-1)) was found in 24.3% of athletes
      and in 12.4% of controls, OR 2.27, P = 0.034. Regular non-professional sport
      activity does not cause an increased rate of anemia or of iron deficiency in
      fertile women. However, physical exercise has an impact on iron status as it
      reduces serum iron and transferrin saturation, and elevates sTfR. Nearly one
      fifth of recreational athletes have anemia and a third have iron deficit, these
      conditions can decrease their physical performance.

PMID- 18092177
TI  - Periprandial changes of the sympathetic-parasympathetic balance related to
      perceived satiety in humans.
AB  - Food intake regulation involves various central and peripheral mechanisms. In
      this study the relevance of physiological responses reflecting the autonomic
      nervous system were evaluated in relation to perceived satiety. Subjects were
      exposed to a lunch-induced hunger-satiety shift, while profiling diverse sensory,
      physiological, and biochemical characteristics at 15 min intervals. Sensory
      ratings comprised questionnaires with visual analogues scales about their feeling
      of satiety, desire to eat, fullness, and hunger. Physiological characteristics
      included heart rate, heart rate variability, and blood pressure, while
      biochemical markers such as cortisol levels and alpha-amylase activity were
      monitored in saliva. The four sensory ratings correlated with heart rate and
      salivary alpha-amylase suggesting a higher sympathetic tone during satiety.
      Furthermore, heart rate variability was associated with age and waist-to-hip
      ratio and cortisol levels negatively correlated with body mass index. Finally,
      neither chewing nor swallowing contributed to a heart rate increase at food
      consumption, but orosensory stimulation, as tested with modified sham feeding,
      caused a partial increase of heart rate. In conclusion, after meal ingestion
      critical physiological alterations reveal a elevated sympathetic tone, which is a
      potential measure of satiety.

PMID- 18092178
TI  - Characterization of cysteine proteases from the carcinogenic liver fluke,
      Opisthorchis viverrini.
AB  - Protease activities in extracts of Opisthorchis viverrini were investigated using
      gelatin zymography and fluorogenic peptide substrates. Using gelatin-impregnated
      X-ray film, 2 microg of O. viverrini excretory-secretory products (Ov-ES) and
      adult somatic extract (Ov-SE) showed proteolytic activity. Zymography of both O.
      viverrini extracts revealed bands at approximately 30 kDa. Using fluorogenic
      peptide substrates, the majority of O. viverrini activity was determined to be
      cathepsin L-like cysteine protease (cleaved Z-Phe-Arg-aminomethylcoumarin (AMC))
      whereas little or no activity was ascribable to other classes of proteases. The
      O. viverrini cysteine protease activity was greatest at pH 6.0 and the activity
      was inhibited by the class-specific inhibitors, E-64 and Z-Ala-CHN2.
      Chromatographic purification of O. viverrini cysteine proteases on thiol
      sepharose enriched for protein(s) of approximately 30 kDa from Ov-ES and Ov-SE.
      The activity profile of the purified enzyme was similar to that of the cathepsin
      L-like activity characterized in Ov-SE and Ov-ES. Furthermore, determination of
      cysteine protease activity in several developmental stages of the parasite
      revealed the highest protease activity in metacercariae soluble extract, followed
      by Ov-ES, egg soluble extract, and Ov-SE. These findings demonstrated that O.
      viverrini has a cathepsin L-like cysteine protease(s) and suggested that abundant
      cysteine protease activity was present in metacercariae where the hydrolase might
      be involved in cyst excystation during mammalian infection.

PMID- 18092179
TI  - Epidemiology of fasciolosis affecting Iberian ibex (Capra pyrenaica) in southern
      Spain.
AB  - Between 1995 and 2006, we surveyed the presence of Fasciola hepatica in Iberian
      ibex (Capra pyrenaica) from Andalucia (southern Spain) by both necropsy (n =
      2,096) and coprological approaches (n = 380). Most of the samples came from the
      Sierra Nevada mountain range (n = 1,884 and 267, respectively), and all positive
      cases involved animals from this location. The prevalence reached 0.53% by
      necropsy and 1.87% by faecal examination. Taking into account both diagnostic
      methodologies and the total number of animals affected (n = 14), we obtained a
      yearly prevalence of 0.7 +/- 0.3%. The infection with F. hepatica was found not
      to be related to host sex, climatology or to co-infection with Sarcoptes scabiei
      (the most important parasite affecting Iberian ibex, with a prevalence of 49.27
      +/- 7.90% in the examined animals). The prevalence of fasciolosis decreased
      significantly during the period under study and this would be explained by an
      increase of ibex resistance to this fluke as a result of a reduction of the
      parasite abundance in the area and/or a reduction of the host infection rate.
      There was no statistical difference between the two diagnostic methods for the
      examination of fasciolosis during the period in which both methods were used.
      Therefore, examination of faecal samples as a non-invasive procedure may provide
      a useful approach for monitoring fasciolosis in wild ungulate populations. The
      results of the present study provided foundation for the effective control of F.
      hepatica infection in Iberian ibex.

PMID- 18092180
TI  - Effect of hyperprolactinaemia on Toxoplasma gondii prevalence in humans.
AB  - Recent studies have shown that hormones could induce anti-parasitic functions of
      the host immune system; thus, the aim of the present study was to estimate the
      seroprevalence of Toxoplasma gondii antibodies by an enzyme-linked immunosorbent
      assay in a Polish population of women and men with hyperprolactinaemia (n = 234)
      and hypoprolactinaemia (n = 41) and in a control group (n = 281) with the
      physiological level of prolactin (PRL). Women with hyperprolactinaemia revealed
      lower seroprevalence than those with normal PRL level (33.90% and 45.58%,
      respectively; p = 0.025). Detailed analysis of the results showed that twofold,
      threefold, fourfold and fivefold increase of the PRL concentration above the
      normal was correlated to the decrease of the T. gondii seroprevalence, but only
      in the group of women with a very high PRL level (>86 ng/ml) seroprevalence
      (12.50%) was significantly lower (p = 0.0004) than in the control subjects. These
      results confirm previously described suggestions on the relationship between
      hyperprolactinaemia and parasitic infection frequency. We postulate that a high
      level of PRL may be one of the important factors preventing T. gondii infection
      in women.

PMID- 18092181
TI  - Significant association of DRD1 with nicotine dependence.
AB  - Epidemiologic studies have strongly implicated genetics in smoking behavior.
      Genes in the dopaminergic system, which mediates the reinforcing and dependence
      producing properties of nicotine, are plausible candidates for roles in nicotine
      dependence (ND). In this study, we examined five single-nucleotide polymorphisms
      (SNPs) within or near the dopamine D(1) receptor gene (DRD1) for their
      association with ND, which was assessed by smoking quantity (SQ), the Heaviness
      of Smoking Index (HSI), and the Fagerstrom Test for ND (FTND). The samples were
      obtained from 2,037 participants representing 200 European American (EA) and 402
      African American (AA) families. Although we found significant associations of
      SNPs rs265973, rs686, and rs4532 in the AA sample; of rs4532 in the EA sample;
      and of rs265975, rs686, and rs4532 in the pooled sample with various ND measures,
      only the association of rs686 in the AA sample and of rs686 and rs4532 in the
      pooled sample remained significant after correction for multiple testing.
      Haplotype-based association analysis revealed that haplotype C-T-A, formed by
      rs265973, rs265975, and rs686, was significantly associated with all three ND
      measures in both the AA and the pooled sample. Another haplotype, T-A-T, formed
      by rs265975, rs686, and rs4532, showed a significant association with FTND in the
      pooled sample. Furthermore, in a luciferase reporter assay, rs686, located in the
      3' untranslated region, caused differential luciferase activities, indicating
      that rs686 is a functional polymorphism affecting expression of DRD1.

PMID- 18092182
TI  - In vivo correlation between c-Fos expression and corticotroph stimulation by
      adrenocorticotrophic hormone secretagogues in rat anterior pituitary gland.
AB  - In the anterior pituitary gland, c-Fos expression is evoked by various stimuli.
      However, whether c-Fos expression is directly related to the stimulation of
      anterior pituitary cells by hypothalamic secretagogues is unclear. To confirm
      whether the reception of hormone-releasing stimuli evokes c-Fos expression in
      anterior pituitary cells, we have examined c-Fos expression of anterior pituitary
      glands in rats administered with synthetic corticotrophin-releasing hormone (CRH)
      intravenously or subjected to restraint stress. Single intravenous administration
      of CRH increases the number of c-Fos-expressing cells, and this number does not
      change even if the dose is increased. Double-immunostaining has revealed that
      most of the c-Fos-expressing cells contain adrenocorticotrophic hormone (ACTH);
      corticotrophs that do not express c-Fos in response to CRH have also been found.
      However, restraint stress evokes c-Fos expression in most of the corticotrophs
      and in a partial population of lactotrophs. These results suggest that c-Fos
      expression increases in corticotrophs stimulated by ACTH secretagogues, including
      CRH. Furthermore, we have found restricted numbers of corticotrophs expressing c
      Fos in response to CRH. Although the mechanism underlying the different responses
      to CRH is not apparent, c-Fos is probably a useful immunohistochemical marker for
      corticotrophs stimulated by ACTH secretagogues.

PMID- 18092184
TI  - Nestin expression in central nervous system germ cell tumors.
AB  - Central nervous system (CNS) germ cell tumors constitute a unique class of rare
      tumors that mainly affect children and adolescents. These tumors are believed to
      originate from displaced primordial germ cells. Recently, results of treatment of
      germ cell tumors have improved with use of radiotherapy and combination
      chemotherapy. However, some tumors have proven refractory to intensive treatment
      with surgery, radiation, and combination chemotherapy. Nestin is an intermediate
      filament protein expressed in undifferentiated cells during CNS development and
      in CNS tumors and is used as a marker of immature elements of tumors, including
      brain tumor stem cells. In this study, we examined for the first time nestin
      expression in 19 CNS germ cell tumors (nine pure germinomas, five germinomas with
      syncytiotrophoblastic giant cells, one yolk sac tumor, one choriocarcinoma, one
      embryonal carcinoma, and two mature teratomas). Nestin was expressed in 14 cases
      but was not expressed in three pure germinomas and two mature teratomas.
      Clinically, nestin-negative tumors did not exhibit dissemination, while all
      tumors that exhibited dissemination also strongly expressed nestin protein. These
      findings suggest that the detection of nestin expression could be useful in the
      management of CNS germ cell tumors, as an auxiliary predictor of dissemination
      and/or progression.

PMID- 18092185
TI  - Influence of yeast population on characteristics of the wine obtained in
      spontaneous and inoculated fermentations of must from Vitis vinifera Lado.
AB  - This work describes the influence of yeast population on the chemical
      characteristics of wine obtained by spontaneous and inoculated fermentation of
      must from Vitis vinifera Lado, a minor white grapevine autochthonous to Galicia
      (NW Spain). The study was carried out for two consecutive years. The results
      showed that musts derived from Lado presented a high acidity though the potential
      alcohol level was acceptable. The genetic diversity of S. cerevisiae strains
      isolated from spontaneous fermentations was low, probably due to must
      characteristics, although these did not interfere with the implantation of the
      commercial strains used. Analyses showed that the wines subsequently produced had
      high alcoholic levels and very high acidities (pH 3.0) as was expected from must
      composition. Wines obtained from spontaneous fermentations had a lower alcohol
      content but higher total acidity than those from inoculated fermentations.
      Monovarietal wines produced from Lado were poorly evaluated in sensorial tests
      because of their unbalanced structure and sourness; however, when they were mixed
      with other autochthonous white varieties with less acidity, the resulting wines
      were well accepted.

PMID- 18092186
TI  - Imaging and the perspective of clinical electrophysiology.

PMID- 18092187
TI  - Compass cutter for periareolar incisions.

PMID- 18092188
TI  - Identification of the sex pheromone of Sesamia cretica Lederer.
AB  - By using solid phase micro-extraction and gas chromatography-mass spectrometry
      analyses, a sex pheromone blend for the stem borer, Sesamia cretica Lederer
      (Lepidoptera, Noctuidae), was identified as consisting of (Z)-9-tetradecen-1-ol
      (80%), (Z)-9-tetradecen-1-yl acetate (10%), and (Z)-11-hexadecen-1-ol (10%). The
      first two components had previously been discovered as attractants for S. cretica
      in field tests, but had not been identified in the female's sex pheromone gland.
      A field-trapping trial showed that the three-component blend gave the highest
      catches of male S. cretica. This blend, in a sticky trap, was used to monitor a
      population of S. cretica in Iran, allowing the seasonal flight activity of this
      insect to be compared with that of a sympatric population of S. nonagrioides. The
      role of pheromones in the reproductive isolation of these species is discussed.

PMID- 18092189
TI  - Real-time analysis of alarm pheromone emission by the pea aphid (acyrthosiphon
      pisum) under predation.
AB  - Upon attack by predators or parasitoids, aphids emit volatile chemical alarm
      signals that warn other aphids of a potential risk of predation. Release rate of
      the major constituent of the alarm pheromone in pea aphids (Acyrthosiphon pisum),
      (E)-b-farnesene (EBF), was measured for all nymphal and the adult stage as aphids
      were attacked individually by lacewing (Chrysoperla carnae) larvae.
      Volatilization of EBF from aphids under attack was quantified continuously for 60
      min at 2-min intervals with a rapid gas chromatography technique (zNose) to
      monitor headspace emissions. After an initial burst, EBF volatilization declined
      exponentially, and detectable amounts were still present after 30 min in most
      cases. Total emission of EBF averaged 16.33 +/- 1.54 ng and ranged from 1.18 to
      48.85 ng. Emission was higher in nymphs as compared to adults. No differences
      between pea aphid life stages were detected for their speed of alarm signal
      emission in response to lacewing larvae attack. This is the first time that alarm
      pheromone emission from single aphids has been reported.

PMID- 18092190
TI  - Interdisciplinary management of pediatric intestinal failure: a 10-year review of
      rehabilitation and transplantation.
AB  - Management of children with intestinal failure is optimized by interdisciplinary
      coordination of parenteral and enteral nutrition support, medical management of
      associated complications, surgical lengthening procedures, and intestinal
      transplantation. Three hundred eighty-nine pediatric patients have been referred
      to our center for interdisciplinary assessment of intestinal failure since 1996
      (median age=1 year; range 1 day-28.8 years). Factors predictive of weaning from
      parenteral nutrition without transplantation included increased mean bowel length
      for patients with gastroschisis (44 vs. 23 cm, p<0.05) and atresia (35 vs. 20 cm,
      p<0.01) and lower mean total bilirubin for patients with NEC (6.1 vs. 12.7 mg/dL,
      p<0.05). Others were also more likely to survive if referred with a lower mean
      total bilirubin (NEC, 7.9 vs. 12.7 mg/dL, p<0.05; pseudo-obstruction, 2.3 vs.
      16.3 mg/dL, p<0.01). Patients weaned from parenteral nutrition by 2.5 years after
      referral achieved 95% survival at 5 years vs. 52% for those not weaned. Bowel
      lengthening procedures were performed on 25 patients. Eight subsequently weaned
      from parenteral nutrition without transplantation. Aggressive medical and
      nutritional intervention along with early referral, intestinal lengthening
      procedures, and intestinal transplantation in children with intestinal failure
      dependent on parenteral nutrition can result in the achievement of enteral
      autonomy and improved survival.

PMID- 18092191
TI  - Identification of early child and family risk factors for aggressive victim
      status in first grade.
AB  - This prospective investigation sought to discriminate children who were both
      aggressive towards and victimized by peers in the first grade, from those who
      were only aggressive, only victimized, or neither (i.e., socially adjusted),
      using early child and family risk factors. Two hundred thirty-eight children,
      their mothers, and teachers participated in a longitudinal study since birth. All
      three aggressor/victim subgroups showed greater temperamental dysregulation than
      the socially adjusted children, but only aggressive victims had significantly
      poorer social perception skills. Aggressive victims were distinguished from
      aggressors by greater exposure to maternal depression and from victims by lower
      levels of early inhibition, but they shared the experiences of negative family
      emotional expressiveness with aggressors and greater mother-child negativity with
      victims. The identification of early risk factors is crucial to prevention and
      early intervention efforts that have the potential to attenuate the long term
      emotional, social, and academic problems associated with aggressive victim
      status.

PMID- 18092193
TI  - Power and public participation in a hazardous waste dispute: a community case
      study.
AB  - Qualitative case study findings are presented. We examined whether public
      participation in a hazardous waste dispute manifested in ways consistent with
      theories of social power; particularly whether participatory processes or
      participants' experiences of them were consistent with the three-dimensional view
      of power (Gaventa, Power and powerlessness: quiescence and rebellion in an
      appalacian valley, 1980; Lukes, Power: A radical view, 1974; Parenti, Power and
      the powerless, 1978). Findings from four data sources collected over 3 years
      revealed that participatory processes manifested in ways consistent with theories
      of power, and participants' experiences reflected this. Results illustrated how
      participation was limited and how citizen influence could be manipulated via
      control of resources, barriers to participation, agenda setting, and shaping
      conceptions about what participation was possible. Implications for community
      research and policy related to participation in hazardous waste disputes are
      discussed.

PMID- 18092192
TI  - Stress generation in adolescent depression: the moderating role of child abuse
      and neglect.
AB  - The present study examined the role of childhood abuse and neglect and depression
      recurrence in moderating the generation of stressful life events in adolescent
      depression. Maltreatment history and stressful life events were assessed using
      two rigorous contextual interviews and rating systems. In a sample of 59
      community depressed adolescents we found significantly higher rates of
      interpersonal events in the 3-month period immediately following depression
      episode onset versus the 3-month period immediately preceding onset in
      adolescents with a history of childhood maltreatment. By contrast, rates of
      events remained constant over a matched period in a control group of non
      maltreated adolescents. Furthermore, the generation of interpersonal events only
      held among those on a first onset of depression. These results suggest that a
      history of childhood abuse and neglect exacerbates the psychosocial dysfunction
      associated with the onset of depression, particularly in the very first episode.

PMID- 18092194
TI  - Results of a population-based screening for hereditary breast cancer in a region
      of North-Central Italy: contribution of BRCA1/2 germ-line mutations.
AB  - BRCA1/2 mutation status is of paramount importance to identify families at risk
      of Hereditary Breast and Ovarian Cancer (HBOC). Most HBOC and BRCA1/2 mutation
      studies have focused on highly selected sub-populations, and few data are
      available for large population cohorts. For this reason, as part of a regional
      cancer prevention strategy in North-Central Italy, we set up a population-based
      screening programme to identify all resident HBOC families, and to determine
      their BRCA1/2 mutation status. To date, 44 different BRCA1/2 variants have been
      identified in 55 HBOC families. Of the seven newly reported mutations, only BRCA1
      Q284X is clearly deleterious. The analysis of clinical disease characteristics in
      relation to age of disease onset and family history showed a difference between
      BRCA1/2 wild type and mutation carrier families. Interestingly, BRCA1/2 mutations
      were significantly more common in women who developed breast cancer <or=40 years
      of age than in BRCA1/2 wild type women (50% vs. 29%, respectively, P = 0.005).
      The family history selection criteria most likely to indicate the presence of
      deleterious BRCA1/2 mutations are breast cancer <or=35 years (P = 0.012), two
      first-degree relatives with breast cancer <or=50 years (P = 0.022), and male
      breast cancer (P = 0.047). The penetrance of BRCA1/2 alterations in our cohort
      seems to be aligned with other published results. However, new data
      interpretations have emerged in relation to the clinical criteria and the
      presence of deleterious mutations. This information shows that a correct and
      accurate clinical selection could avoid unnecessary molecular tests and could
      better address genetic analysis and clinical management.

PMID- 18092195
TI  - Nonalcoholic fatty liver disease and diabetes mellitus.

PMID- 18092196
TI  - Insulin therapy in type 2 diabetes.

PMID- 18092197
TI  - The evaluation of cardiac and peripheral arterial disease in patients with
      diabetes mellitus.

PMID- 18092198
TI  - Developmental changes in the expression levels of alternative first exons of
      prolactin receptor gene in rat brain.
AB  - One of the alternative first exons, E1(4), of the rat prolactin receptor (PRLR)
      gene was identified 5.4 kb downstream of exon 2 by sequence analysis of a rat
      genomic clone. In female and male rat brains, expression levels of E1(4)
      containing PRLR mRNA increased remarkably between 2 and 4 weeks of age during
      postnatal development, whereas the levels of PRLR mRNAs containing other first
      exons, E1(3) and E1(5), did not change throughout the development. The levels of
      E1(4)-containing PRLR mRNA in the female rats at 8 weeks of age decreased by
      ovariectomy, and recovered by the administration of 17beta-estradiol, whereas
      castration and following testosterone treatment showed no effect on the levels of
      E1(4)-containing PRLR mRNA in the male rats. The levels of E1(3)- and E1(5)
      containing PRLR mRNAs were not affected by gonadectomy and following sex steroid
      hormone treatments in both sexes. These results indicate that expression of PRLR
      gene in the female and male rat brains increases during postnatal development due
      to the transcriptional activation of the E1(4) first exon.

PMID- 18092199
TI  - Measurement accuracy of marginal bone level in digital radiographs with and
      without color coding.
AB  - OBJECTIVE: New radiographic techniques have made it possible to color-code intra
      oral digital radiographs. The purpose of the present study was to compare the
      accuracy and precision of marginal bone level measurements in digital radiographs
      with and without color coding. MATERIAL AND METHODS: Periapical digital
      radiographs of 21 patients were processed with and without a color-coding
      algorithm. The patients had periodontal surgery immediately after exposure of
      radiographs, and vertical distances from the cemento-enamel junction (CEJ) to the
      most apical part of the marginal bone were measured clinically. The measured
      values were considered as a reference standard and subtracted from the
      corresponding radiographic vertical distance. Seven observers contributed to the
      radiographic measurements under the same viewing conditions. RESULTS: No
      statistically significant differences were found between absolute differences of
      vertical distances obtained from radiographs and their corresponding reference
      standards in the two types of radiograph. Intra- and inter-observer variability
      was not significant. CONCLUSION: Color-coded digital radiographs did not provide
      a more favorable accuracy when assessing marginal alveolar bone levels than black
      and-white radiographs and thus did not improve measurement of such levels.

PMID- 18092200
TI  - The erosion-inhibiting effect of TiF4, SnF2, and NaF solutions on pellicle
      covered enamel in vitro.
AB  - OBJECTIVE: The aim of this study was to compare the protective effect of TiF(4),
      SnF(2), and NaF treatment on the development of erosion-like lesions in pellicle
      covered human enamel. MATERIAL AND METHODS: Twelve human molars were each divided
      into 5 specimens, 4 of which were immersed in saliva for 2 h. Three pellicle
      covered specimens from each tooth were treated with a TiF(4), SnF(2), or NaF
      solution (all 0.5 M F) for 2 min. Control specimens, one with and one without
      pellicle, were included. Immersion in acid (0.01 M HCl) was carried out stepwise
      (2+2+2+2 min). The etching depths (in microm) were measured using white light
      interferometry. RESULTS: Compared with the control with pellicle, TiF(4) reduced
      enamel loss by 100% after 2 min and by 24% after 8 min of acid exposure. The
      corresponding values for SnF(2) were 45% and 14%. NaF provided no significant
      protection of the surface. The pellicle-covered specimens showed reduced lesion
      depths after 6 and 8 min compared to the controls without pellicle. CONCLUSIONS:
      TiF(4) gave the best protection against acid attack. SnF(2) provided significant
      protection only after 2 min of acid exposure, while NaF had no significant
      protective effect.

PMID- 18092201
TI  - Giving low priority to oral health care. Voices from people with disabilities in
      a grounded theory study.
AB  - OBJECTIVE: Our knowledge of how people with disabilities look upon oral health
      and dental care is limited. The aim of this study was thus to explore how the
      people with disabilities experience the encounter with dental health care.
      MATERIAL AND METHODS: With a focus on dental care and oral health, qualitative
      interviews with 16 informants with cognitive and/or physical disabilities were
      analysed in accordance with the qualitative method of grounded theory. RESULTS: A
      core category identified and labeled "giving low priority to oral health care"
      was found to be related to four other categories: "being afraid of losing
      control", "having difficulties complying with instructions", "having a desire for
      continuity", and "wishing to be just like everyone else". The results show that
      oral health and dental care are important, but are not considered a priority by
      the people with disabilities. General health issues have much higher priority but
      do not include oral health, which consequently can affect oral health negatively.
      CONCLUSIONS: Of several factors identified that could be improved to make dental
      visits more pleasant for patients are enhancing a sense of control in the patient
      and improving continuity.

PMID- 18092202
TI  - Effect of pepsin on erosive tissue loss and the efficacy of fluoridation measures
      in dentine in vitro.
AB  - OBJECTIVES: In dentine, erosive lesion progression and efficacy of fluoridation
      measures for symptomatic therapy of dental erosion are both dependent on the
      presence of the organic matrix. In patients with eating disorders in combination
      with chronic vomiting, the demineralized organic matrix can be degraded by
      gastric enzymes. The aim of this study was to investigate the effect of pepsin on
      erosion progression and the efficacy of fluoride in dentine. MATERIAL AND
      METHODS: Human dentine specimens were prepared and randomly divided into 4 groups
      of 20 specimens each. They were subjected to a cyclic de- and remineralization
      procedure for 9 days. For demineralization (6 x 2 min per day), an HCl solution
      (pH 1.6) was used in all groups. In two groups, pepsin (1.5 mg mL(-1)) was added
      to the demineralization solution. Fluoridation was performed in two groups 6 x 1
      min per day with a mouth rinse (Olaflur/SnF(2); 250 ppm F(-)) after
      demineralization with both the HCl solution and the pepsin containing solution.
      Degradation of collagen was quantified by analyzing hydroxyproline and tissue
      loss was determined microradiographically. SEM images were taken in addition.
      RESULTS: In the pepsin group, 1.72 (0.26) microg mL(-1) (mean (SD))
      hydroxyproline per day was detected, and in the pepsin-fluoride group 1.95 (0.50)
      microg mL(-1). Tissue loss after 9 days in the control group was similar to that
      in the pepsin group (122.2 (53.4) microm and 122.2 (38.0) microm, n.s.,
      respectively). Fluoridation reduced tissue loss after demineralization (98.8
      (30.2) microm) but not after pepsin treatment (125.2 (34.2) microm; p< or =0.05).
      CONCLUSION: Under the conditions used, pepsin had no influence on tissue loss,
      but altered the efficacy of fluoridation measures.

PMID- 18092203
TI  - Bond strength between a silica glass-fiber-reinforced composite and artificial
      polymer teeth.
AB  - OBJECTIVE: A resin-bonded prosthesis is preferred when conservation of abutment
      tooth structure is required, although a problem with such systems is bonding
      between the fixed partial denture material and a polymer pontic. The aim of this
      study was to investigate the bond strength of a silica glass-fiber-reinforced
      composite to polymer teeth compared with the bond strength of a proprietary heat
      polymerized denture base polymer and also between a layer of the polymerized
      matrix polymer of the experimental base material and an additional layer of the
      same material. MATERIAL AND METHODS: Polymeric artificial maxillary incisors and
      two heat-polymerized base materials (ProBase Hot and an experimental formulation)
      were used. Three test groups (each n=6) were prepared: bonding between artificial
      tooth and an experimental composite (group-TC), bonding between tooth and ProBase
      Hot (group-TP), and bonding between experimental base material and experimental
      base material (group-BB). The content of inorganic particles of teeth was
      determined by combustion analysis. The bond strengths were measured in shear with
      a universal testing machine and the data were analyzed by one-way ANOVA and post
      hoc Scheffe test (p<0.05). After failure, the fracture surfaces were examined by
      optical microscopy. RESULTS: The content of inorganic particles in the teeth was
      low. There is no statistically significant difference in bond strength between
      the groups. CONCLUSIONS: Bond strength of the experimental composite to
      artificial polymer teeth was as good as that of a conventional heat-polymerized
      denture base polymer. The strong bonding between the experimental material and
      artificial teeth makes this combination suitable for resin-bonded prostheses.

PMID- 18092204
TI  - Race: the extinction of a paradigm.

PMID- 18092205
TI  - Are Americans shorter (partly) because they are fatter? A comparison of US and
      Dutch children's height and BMI values.
AB  - OBJECTIVE: The study compared the height and BMI values of US children and youth
      by gender in the most recent NHANES surveys (1999-2004) to those of their Dutch
      counterparts in 1997 in order to gain insights into the different growth
      patterns. RESULTS: US children and youth are both shorter and heavier than their
      Dutch counterparts. US adolescent girls tend to experience an earlier growth
      spurt than do the Dutch and the velocity of growth of US boys slows down faster
      after the adolescent growth spurt than does that of their Dutch counterparts. The
      latter end up being approximately 5.6 cm taller and their median BMI values are
      1.9-2.0 less than that of US youth between the ages of 10 and 19. This implies
      that US boys of the same height at age 19 are 8.8 kg heavier than their Dutch
      counterparts, and girls of age 13 are 7.2 kg heavier. DISCUSSION: Some studies
      link high BMI values in childhood to an earlier onset of adolescence, which in
      turn has been linked to less growth thereafter. CONCLUSION: The fast tempo of
      growth of the US children may be associated with high energy balance, which leads
      to higher BMI values and which in turn may be associated with less growth during
      adolescence.

PMID- 18092206
TI  - Consanguinity affects selection of alpha-thalassemia genotypes and the size of
      populations under selection pressure from malaria.
AB  - BACKGROUND: In populations with alpha(+)-thalassemia gene deletion, the practice
      of consanguineous marriages is common. AIM: The study explored the impact of
      consanguinity (inbreeding) on the selection of alpha(+)-thalassemia genotypes in
      a computer model. METHOD: In a population under selection pressure from malaria,
      a single protective mutation (-alpha/alphaalpha genotype) was introduced among
      normal genotypes (alphaalpha/alphaalpha), and mating allowed to proceed.
      Heterozygote (-alpha/alphaalpha) and homozygote (-alpha/-alpha) children were 1.5
      and 2.5 times more likely to survive malaria than those with normal genotypes.
      Using different coefficients of inbreeding (F, range 0-0.12), we examined the
      effect of population size, and the mean number of generations required for the
      homozygote frequency to reach 0.5. RESULTS: On average, consanguineous
      populations were larger than randomly mating populations and the size was
      directly proportional to F. In more inbred populations,-alpha/-alpha homozygotes
      reached a frequency of 0.5 faster than in less inbred populations. As the
      frequency of the alpha(+)-thalassemia allele in a population increases, however,
      the positive effect of inbreeding on the population growth decreases. CONCLUSION:
      Under selection pressure from malaria, consanguinity may increase the speed of
      selection of-alpha/-alpha homozygotes and provide an advantage regarding
      population growth over non-consanguineous populations.

PMID- 18092207
TI  - Role of individual and household level factors on stunting: a comparative study
      in three Indian states.
AB  - BACKGROUND: Status of growth especially in early childhood is not only the most
      important determinant of health of a child but also a reflection of the well
      being of the entire society. The extent of malnutrition in India is very high,
      but the exact magnitude varies considerably depending on which indicator is used.
      Child health in this paper is measured through chronic malnutrition (termed as
      stunting). Three states were selected, namely Bihar, West Bengal and Kerala.
      These three states represent the three stages of development. Bihar is one of the
      least and Kerala is one of the most developed states in India. AIM: The present
      paper aims to investigate the degree of chronic malnutrition in the context of
      socio-economic, demographic and other characteristics of the children and their
      households in the three selected states in India. SUBJECTS AND METHODS: The data
      for this study were taken from the National Family Health Survey (NFHS-2)
      conducted by the International Institute for Population Sciences (IIPS), Mumbai,
      in 1998-1999. The NFHS-2 sample covers ever-married women in the age group 15-49
      years from 26 states in India. Besides collecting information on health, the
      survey collects data on socio-economic and demographic characteristics at
      individual and household level. RESULTS: The percentage of stunting of children
      in Bihar, West Bengal and Kerala was found to be 54, 39 and 23%, respectively.
      Regression analysis showed that the major factors that significantly influenced
      the status of health in the children in all three states were women's education
      and the household condition index. Months of breastfeeding and birth interval
      also had some association with health status. The effect of the above-mentioned
      variables was most prominent in Bihar and least in Kerala in terms of statistical
      significance. CONCLUSION: There is a close positive link between the nutritional
      status of pre-school children and the stages of development of the states.
      Mothers' education and household condition are important influences on children's
      health status irrespective of the stage of development.

PMID- 18092208
TI  - Early life and current determinants of bone in South African children of mixed
      ancestral origin.
AB  - BACKGROUND: The influence of early life factors on the bone mineral density of
      children has been identified, however the contribution of these determinants may
      vary. AIM: The study investigated determinants of bone mineral content (BMC) in
      South African children of mixed ancestral origin. SUBJECTS AND METHODS: Early
      life data including birth weight, maternal alcohol consumption and smoking during
      pregnancy were collected on 9-year-old children of mixed ancestral origin (n =
      64). Grip strength was measured, and physical activity, housing density and
      dietary data were collected. Whole body BMC (WB BMC), fat-free soft tissue and
      fat tissue were measured using dual energy X-ray absorptiometry. RESULTS:
      Maternal alcohol consumption during pregnancy was associated with WB BMC, however
      after adjusting for possible confounders, this was no longer significant. When
      combined with gender, gestational age and maternal BMC in a multiple regression,
      maternal alcohol consumption during pregnancy could explain 20% of the variance
      in the WB BMC, however when current height was included in the model, the
      contribution of the other factors was insignificant. There was however a
      significant correlation between current height and birth weight (r = 0.34; p <
      0.01) and alcohol consumption during pregnancy (r = 0.34; p < 0.05). A model
      consisting of current factors such as age, weight, gender, grip strength and
      calcium intake was able to explain 81.5% of the variance. Housing density was
      negatively correlated with WB BMC (r =-0.11; p = 0.05). CONCLUSION: These data
      suggest that although early life factors may contribute indirectly to the bone
      mass of children of mixed ancestral origin, the contribution of current factors
      is greater. In addition, environmental factors such as housing density have a
      direct effect on bone mass, independent of body size.

PMID- 18092209
TI  - Why is the body mass index calculated as mass/height2, not as mass/height3?
AB  - BACKGROUND: The body mass index or BMI, mass/height(2), is used to predict
      fatness and health. It is an approximation to the Benn index, mass/height(p),
      where p (typically 1.1-2.5 for adult populations) makes the index uncorrelated
      with height. Mass/height(3) is an index of body build that is independent of
      scale and statistics. AIM: To explain why p varies and is less than three, show
      how statistical methods can distort perceptions of mass-height relationships, and
      clarify the nature of the BMI. METHODS: A hypothetical adult population is
      modelled statistically, with mass being approximately proportional to height(3)
      and with neither variable determining the other. Values of p are calculated both
      for the model and for real adults. RESULTS: In both cases p increases with the
      correlation between mass and height. Both p and that correlation are usually
      lower for women than for men. CONCLUSIONS: In adult populations mass must vary
      more nearly with height(3) than with height(2), although, for reasons explained,
      conventional statistical techniques suggest otherwise. Nevertheless the BMI is a
      valid predictor of fatness from mass and height in adults and is properly
      divisible into fat mass and fat-free mass indices. The validity of the latter
      three indices for children is questionable.

PMID- 18092210
TI  - The relationship between body composition and onset of menarche.
AB  - BACKGROUND: A late age of menarche in elite adolescent athletes is frequently
      attributed to low body fat/weight. If a critical body weight/fat is necessary for
      menarche, a reduction in the variability of these parameters would be observed at
      menarche compared to times before and after this event. AIM: The study determined
      the variability in body mass (BM), per cent body fat (%BF) and total body fat
      (TBF) of girls between -2 and +2 years from menarche. METHODS: Participants were
      part of the Saskatchewan Pediatric Bone Mineral Accrual Study (1991-1998). Body
      composition was assessed using dual X-ray absorptiometry (DXA). An individual's
      data was retained for analysis if they had at least four DXA scans between -3 and
      +3 years from menarche. Values were interpolated from the cubic spline at whole
      years between -2 and +2 years from menarche. Coefficient of variation (CV) was
      used to assess variability. RESULTS/CONCLUSION: Data on 61 girls were retained
      for analysis. The range in BM, TBF and %BF at menarche was 50.10 kg, 35050.06 g
      and 31.61%, respectively. Reductions in variability of body fat and weight were
      not apparent at menarche, which does not provide support for the hypothesis that
      a critical body weight/fat is required for menarche.

PMID- 18092213
TI  - Congenital heart disease and consanguineous marriage in South India.

PMID- 18092215
TI  - Balanus amphitrite or Amphibalanus amphitrite? A note on barnacle nomenclature.
AB  - In a recent revision of the Balanidae based on morphological systematics, the
      much studied fouling species Balanus amphitrite was renamed Amphibalanus
      amphitrite. Here, the case is made for retaining the former nomenclature.
      Taxonomists are urged to exercise caution before introducing new formal
      taxonomies, which should ideally be based on several independent lines of
      evidence.

PMID- 18092216
TI  - Extracts of North Sea macroalgae reveal specific activity patterns against
      attachment and proliferation of benthic diatoms: a laboratory study.
AB  - A variety of macroalgae (Ceramium rubrum, Corallina officinalis, Palmaria
      palmata, Mastocarpus stellatus, Fucus vesiculosus, Cladophora rupestris, Ulva
      sp.) were investigated by scanning electron microscopy to visualize epiphytic
      colonizers. The macroalgae differed in terms of their epiphytic coverage of
      bacteria, fungi and diatoms. Macroalgae, largely devoid of epiphytic diatoms,
      were hypothesized to employ effective antifouling means to reduce epiphytic
      coverage, whilst heavily fouled macroalgae were proposed to lack antifouling
      strategies. To test these hypotheses from an allelochemical perspective with
      regard to fouling diatoms, dichloromethane-methanol (1:1) crude extracts of
      macroalgae were concentrated in dimethylsulfoxide and investigated in diatom
      attachment and proliferation assays using four benthic diatoms (Nitzschia sp.,
      Navicula phyllepta, Navicula arenaria and Amphora sp.). Algal extracts exhibited
      a distinct pattern of activity against the test diatoms, suggesting a targeted
      and selective effect of macroalgal metabolites on individual fouling diatoms. The
      main outcome of this study was that visual inspection and quantitative
      categorization of epiphytic colonizers on macroalgal thalli could not be used to
      predict reliably whether macroalgae employed a chemical defense mechanism.

PMID- 18092217
TI  - Methodological variables in choral reading.
AB  - This preliminary study explored changes in prosodic variability during choral
      reading and investigated whether these changes are affected by the method of
      eliciting choral reading. Ten typical adult talkers recorded three reading
      materials (poetry, fiction and textbook) in three reading conditions: solo
      (reading aloud alone), track (reading aloud with a recording), and choral
      (reading aloud with another live talker). Measurements of fundamental frequency,
      amplitude, and vowel duration variability were performed. Compared to solo
      reading, choral reading featured decreased variability of fundamental frequency,
      amplitude, and vowel duration. In track reading, only decreased fundamental
      frequency variability was observed, while vowel duration variability increased.
      Track reading also contained significantly more errors than choral or solo
      reading. The reading material used did not significantly affect the prosodic
      features of talkers' speech, but did affect talkers' error rate. These results
      suggest that, in studies of choral reading as a fluency-evoking condition, track
      reading might not be an appropriate substitute. In addition, the text used may
      affect fluency in these conditions. These results also have theoretical
      implications for studies of how talkers manipulate and execute the prosodic
      features of speech.

PMID- 18092218
TI  - Narrative organization skills in children with attention deficit hyperactivity
      disorder and language impairment: application of the causal network model.
AB  - Studies suggest that the oral narratives of children with attention deficit
      hyperactivity disorder (ADHD) are less organized than those of typically
      developing peers. Many studies, however, do not account for children's language
      abilities. Because language impairment (LI) is a frequent comorbid condition in
      children with ADHD, this exploratory study investigated language abilities and
      narrative organization skills in children with and without ADHD. Narratives were
      elicited using the picture-sequence task and the single-picture task from the
      Test of Narrative Language (Gillam & Pearson, 2004). The causal network model
      (Trabasso, Van den Broek, & Suh, 1989) was applied to analyse the narratives.
      Specifically, narratives were examined to identify complete and incomplete
      superordinate and subordinate Goal-Attempt-Outcome (GAO) units. The results
      revealed no differences among the groups in the picture-sequence task. Children
      with ADHD+LI produced significantly fewer complete superordinate GAO units than
      typical children in the single-picture task. Theoretical and clinical
      implications are discussed.

PMID- 18092219
TI  - Lexical diversity and productivity in French preschoolers: developmental, gender
      and sociocultural factors.
AB  - In this study, we examined the influence of child gender and sociocultural (SCL)
      factors in language production. Subjects were French Parisian children in nine
      age groups (24, 27, 30, 33, 36, 39, 42, 45 and 48 months). A total of 316
      language samples were recorded during a 20-min standardized play session.
      Measures of grammatical and lexical development included Mean Length of Utterance
      (MLU) and word type and token - specifically, grammatical words such as
      determiners, prepositions and pronouns as well as verbs. ANOVAs revealed strong
      influences of SCL, with children from high SCL families showing more complex
      lexical productions and a higher rate of development. These observations suggest
      that amount of exposure to language accounts for this differential rate of
      acquisition. Analyses also revealed a general effect of gender, showing a small
      advantage in language production for girls over boys until 36 months of age.

PMID- 18092220
TI  - Judging stuttering in an unfamiliar language: the importance of closeness to the
      native language.
AB  - In order to test the hypothesis that closeness to the listener's native language
      is a determining factor when identifying stuttering in an unfamiliar language,
      three panels of different linguistic background were asked to make judgements of
      stuttering in a sample of Dutch speakers. It was found that a panel speaking
      Dutch and a panel speaking English (both West Germanic languages) performed
      better in identifying Dutch people who stutter and people who do not stutter than
      a panel speaking Brazilian Portuguese (a Romance language) thus confirming the
      existence of a closeness of language influence. Further analysis showed that when
      the native language is more remote from the unfamiliar language there is the
      possibility of a higher risk for false positive identification.

PMID- 18092221
TI  - Perception of the auditory-visual illusion in speech perception by children with
      phonological disorders.
AB  - An example of the auditory-visual illusion in speech perception, first described
      by McGurk and MacDonald, is the perception of [ta] when listeners hear [pa] in
      synchrony with the lip movements for [ka]. One account of the illusion is that
      lip-read and heard speech are combined in an articulatory code since people who
      mispronounce words respond differently from controls on lip-reading tasks. A same
      different judgment task assessing perception of the illusion showed no difference
      in performance between controls and children with speech difficulties. Another
      experiment compared children with delayed and disordered speech on perception of
      the illusion. While neither group perceived many illusions, a significant
      interaction indicated that children with disordered phonology were strongly
      biased to the auditory component while the delayed group's response was more
      evenly split between the auditory and visual components of the illusion. These
      findings suggest that phonological processing, rather than articulation, supports
      lip-reading ability.

PMID- 18092222
TI  - Editorial: in praise of cognitive neuropsychiatry.

PMID- 18092223
TI  - Deception and false belief in paranoia: modelling theory of mind stories.
AB  - BACKGROUND: This study used Item Response Theory (IRT) to model the psychometric
      properties of a Theory of Mind (ToM) stories task. The study also aimed to
      determine whether the ability to understand states of false belief in others and
      the ability to understand another's intention to deceive are separable skills,
      and to establish which is more sensitive to the presence of paranoia. METHOD: A
      large and diverse clinical and nonclinical sample differing in levels of
      depression and paranoid ideation performed a ToM stories task measuring false
      belief and deception at first and second order. RESULTS: A three-factor IRT model
      was found to best fit the data, consisting of first- and second-order deception
      factors and a single false-belief factor. The first-order deception and false
      belief factors had good measurement properties at low trait levels, appropriate
      for samples with reduced ToM ability. First-order deception and false beliefs
      were both sensitive to paranoid ideation with IQ predicting performance on false
      belief items. CONCLUSIONS: Separable abilities were found to underlie performance
      on verbal ToM tasks. However, paranoia was associated with impaired performance
      on both false belief and deception understanding with clear impairment at the
      simplest level of mental state attribution.

PMID- 18092224
TI  - Dissociating the components of inhibitory control involved in predisposition to
      hallucinations.
AB  - INTRODUCTION: We have previously linked hallucinations in schizophrenia and
      hallucination predisposition to poor intentional inhibition. However, these
      previous studies have not systematically investigated the separable dimensions of
      inhibitory control involved, namely, intentional versus unintentional, and
      inhibition versus resistance to interference. The aim of this study was to
      clarify the critical component(s) of inhibitory control specifically related to
      hallucination predisposition. METHODS: The Launay-Slade Hallucination Scale
      Revised (LSHS-R) was completed by 589 undergraduate students, from which high-
      (n=28) and low- (n=25) hallucination predisposition groups were drawn.
      Participants were administered tasks measuring unintentional inhibition (Brown
      Peterson variant task) and intentional resistance to interference (directed
      ignoring [DI] task). RESULTS: The high LSHS-R group showed significant
      difficulties relative to the low LSHS-R group on the DI task only; although these
      differences did not remain significant when controlling for anxiety or delusional
      thinking. Regression analyses showed that anxiety, but not delusional thinking,
      independently contributed to variance in DI task performance above that accounted
      for by hallucination predisposition. CONCLUSIONS: Intentional rather than
      unintentional control of intrusive cognitions appears to play an important role
      in hallucination predisposition. The results indicate that difficulties with the
      intentional resistance to interference from concurrent external distractors may
      be a common mechanism underlying positive schizophrenia symptoms and anxiety.
      However, given previous findings reported by Paulik, Badcock, and Maybery (2007),
      we propose that hallucination predisposition is also characterised by a
      difficulty with the active suppression of intrusive cognitions - that is,
      intentional inhibition - which is not shared with anxiety or delusional symptoms.

PMID- 18092225
TI  - Atypical unfamiliar face processing in Williams syndrome: what can it tell us
      about typical familiarity effects?
AB  - INTRODUCTION: Familiar and unfamiliar face perception is typically dissociated by
      the relative use of internal and external face features. The Williams syndrome
      (WS) social phenotype emphasises hypersociability, with an interest in
      interacting with people irrespective of familiarity. The aim is to explore
      whether unfamiliar face processing is characterised by the typical dissociation
      between internal and external features in WS, or whether the social stimulus
      drive towards strangers is linked to atypicalities of unfamiliar face processing.
      METHOD: The procedure replicates that previously used with typically developing
      children. Participants with WS (aged 10-18 years) and typically developing
      comparison participants determine whether two face parts are from the same person
      or different people, using the whole face, internal, and external features.
      RESULTS: Only participants with WS, and not typically developing participants,
      show greater accuracy matching unfamiliar faces from internal than external
      features. CONCLUSIONS: Evidence of atypical unfamiliar face processing in WS may
      inform models of typical face perception, revealing the origins of the relative
      advantage for internal features typically associated with familiar but not
      unfamiliar faces. The results also have implications for understanding more
      clearly the social phenotype associated with WS.

PMID- 18092226
TI  - Facial emotion space in schizophrenia.
AB  - INTRODUCTION: Previous studies show that patients with schizophrenia have a
      deficit in facial emotion recognition. In the framework of emotion categorisation
      theories, the purpose of the present study was to test if this impairment could
      result from abnormal boundaries between emotions (whether these boundaries are
      shifted along continuums or are less sharpened). METHOD: Twenty-six schizophrenic
      patients and the same number of healthy participants were required to perform a
      facial emotion recognition task and an emotion categorisation task with different
      emotion intensities obtained using morphing techniques. RESULTS: The main results
      indicate that schizophrenic patients exhibited an emotion space with less
      sharpened categories which favoured confusion between different emotions and
      intrusions of other emotions. Moreover, correlations between different indices
      showed that the less sharpened the categories, the more frequent the intrusions
      and the less discriminable the facial emotions. CONCLUSION: We conclude that
      patients with schizophrenia process facial expressions in a less categorical way
      which involves impaired recognition of facial expressions. Such a specific
      impairment may favour false perceptions and lead to the settlement of delusional
      ideas.

PMID- 18092230
TI  - Coordinate regulation of ribosome biogenesis and function by the ribosomal
      protein S6 kinase, a key mediator of mTOR function.
AB  - Current understanding of the mechanisms by which cell growth is regulated lags
      significantly behind our knowledge of the complex processes controlling cell
      cycle progression. Recent studies suggest that the mammalian target of rapamycin
      (mTOR) pathway is a key regulator of cell growth via the regulation of protein
      synthesis. The key mTOR effectors of cell growth are eukaryotic initiation factor
      4E-binding protein 1 (4EBP-1) and the ribosomal protein S6 kinase (S6K). Here we
      will review the current models for mTOR dependent regulation of ribosome function
      and biogenesis as well as its role in coordinating growth factor and nutrient
      signaling to facilitate homeostasis of cell growth and proliferation. We will
      place particular emphasis on the role of S6K1 signaling and will highlight the
      points of cross talk with other key growth control pathways. Finally, we will
      discuss the impact of S6K signaling and the consequent feedback regulation of the
      PI3K/Akt pathway on disease processes including cancer.

PMID- 18092231
TI  - Roles of transforming growth factor-alpha in mammary development and disease.
AB  - Transforming growth factor-alpha (TGFalpha) is a member of the epidermal growth
      factor (EGF) family. Expression of TGFalpha is highly regulated in response to
      exogenous cellular signals including cytokines and other growth factors. The
      growth factor has been found to be indispensable for proper development of many
      tissues and organs. TGFalpha has also been implicated in numerous disease states
      including forms of breast cancer. This minireview summarizes the basic biology of
      TGFalpha and its actions during normal and pathogenic development of the mammary
      epithelium.

PMID- 18092232
TI  - In vitro culture of testicular germ cells: regulatory factors and limitations.
AB  - Spermatogenesis is regulated mainly by endocrine factors and also by testicular
      paracrine/autocrine growth factors. These factors are produced by Sertoli cells,
      germ cells, peritubular cells and interstitial cells, mainly Leydig cells and
      macrophages. The interactions and the ratio between Sertoli and germ cells in the
      seminiferous tubules ensure successful spermatogenesis. In order to culture
      spermatogonial stem cells (SSCs) in vitro, researchers tried to overcome some of
      the obstacles -- such as the low number of stem cells in the testis, absence of
      specific markers to identify SSCs -- in addition to difficulties in keeping the
      SSCs alive in culture. Recently, some growth factors important for the
      proliferation and differentiation of SSCs were identified, such as glial cell
      line derived neurotrophic factor (GDNF), stem cell factor (SCF) and leukemia
      inhibitory factor (LIF); also, markers for SSCs at different stages were
      reported. Therefore, some groups succeeded in culturing SSCs (under limitations),
      or more differentiated cells and even were able to produce in vitro germ cells
      from embryonic stem cells. Thus, success in culturing SSCs is dependent on
      understanding the molecular mechanisms behind self-renewal and differentiation.
      Culture of SSCs should be a good tool for discovering new therapeutic avenue for
      some infertile men or for patients undergoing chemotherapy/radiotherapy (pre
      puberty or post-puberty).

PMID- 18092233
TI  - HB-EGF promotes angiogenesis in endothelial cells via PI3-kinase and MAPK
      signaling pathways.
AB  - OBJECTIVE: Heparin-binding EGF-like growth factor (HB-EGF) belongs to the
      epidermal growth factor (EGF) superfamily of ligands. It has been implicated as a
      regulator of angiogenesis. However, the mechanisms by which HB-EGF promotes
      angiogenesis are unknown. The goal of the present study was to define the
      pathways by which HB-EGF stimulates angiogenesis in endothelial cells. METHODS:
      To characterize the angiogenic activity of HB-EGF, we treated human umbilical
      vein endothelial cells (HUVEC) with HB-EGF and analyzed the effects on cell
      proliferation, migration and tube formation. Side-by-side assays with EGF were
      used for comparison. RESULTS: Both HB-EGF and EGF stimulated HUVEC migration in
      scratch assays and promoted vascular tube formation in 2D-angiogenesis assays,
      without inducing cell proliferation. HB-EGF- and EGF-induced HUVEC migration and
      capillary tube formation were dependent upon activation of PI3K, MAPK and eNOS.
      Importantly, HB-EGF-and EGF-induced tube formation was comparable to, but were
      independent of tube formation induced by VEGF. CONCLUSIONS: We have demonstrated
      that HB-EGF and EGF induce angiogenesis via activation of PI3K, MAPK and eNOS in
      a VEGF-independent fashion. Thus, the role played by HB-EGF in stimulating
      physiologic processes such as wound healing in vivo may be dependent, in part, on
      its ability to promote angiogenesis.

PMID- 18092234
TI  - Expression and localization of insulin-like growth factor-I in four parts of the
      red deer antler.
AB  - The expression and localization of insulin-like growth factor-I (IGF-I) in the
      four parts (tip, upper, mid and base) of the red deer antler has been extensively
      investigated. We used reverse transcriptase polymerase chain reaction (RT-PCR)
      and real-time reverse transcriptase polymerase chain reaction (real time RT-PCR),
      in situ hybridization, immunohistochemistry and Western blot techniques to
      localize IGF-I messenger ribonucleic acid (mRNA) and IGF-I peptide in the four
      parts of the antler. The specific sequence encoding IGF-I was detected by RT-PCR
      in all of the four specimens, and the 395 bp IGF-I sequence from the red deer
      antler was shown to have very high homology with human, goat and mouse IGF-I. In
      situ hybridization and immunohistochemistry results demonstrated that the
      expression of IGF-I occurred in chondrocytes and osteoblasts in the tip and upper
      parts of the antler. However, IGF-I was only detectable in osteoblasts around the
      bone in the mid and base parts. There were significant differences in the
      intensity of the signal obtained with the IGF-I probe in the tip, upper, mid and
      base tissues. The Western blot analysis also provided evidence that IGF-I
      expression was localized differentially in the four parts of the deer antler.
      This study indicates that antler tissue is an essential part of the IGF system,
      which is involved in the regulation of the growth of red deer antlers. The
      specific expression of IGF-I in the four parts of the deer antler suggests that
      the IGF-I molecule is present at significantly different levels throughout the
      deer antler development and regeneration processes. Localization of IGF-I in
      chondrocytes and osteoblasts suggests that IGF-I may play an important role in
      cartilage and bone formation. In addition, it may have a variety of biophysical
      effects that influence the rapid growth of deer antlers.

PMID- 18092235
TI  - Progranulin is a stress-response factor in fibroblasts subjected to hypoxia and
      acidosis.
AB  - The growth factor progranulin (granulin-epithelin precursor, PC-derived growth
      factor or acrogranin) regulates proliferation and migration and is implicated in
      cancer, development, wound repair and neurodegenerative diseases. Under most
      conditions fibroblasts do not express progranulin in vivo, however its expression
      is activated following wounding. We hypothesised that progranulin is part of a
      fibroblast stress response. Fibroblasts in culture were exposed to two
      physiologically and clinically relevant microenvironmental stresses; hypoxia (1%
      oxygen) and acidosis, both of which increase progranulin expression. The greatest
      increases occurred when hypoxia and acidosis were combined. Increased progranulin
      expression is not a direct response to apoptosis since it occurred under
      conditions of pH and hypoxia under which cell viability remained high. Low
      concentrations of progranulin (2 nM) protected fibroblasts from apoptosis induced
      by extreme acidosis (pH 5.0 and 4.0). We propose that progranulin is part of a
      fibroblast stress response and is cytoprotective to acidotic stress.

PMID- 18092236
TI  - Cardioprotective role of cardiotrophin-1 gene transfer in a murine model of
      myocardial infarction.
AB  - We observed the effect of cardiotrophin-1 (CT-1) gene transfer on cardiomyocytes
      in a murine model of myocardial infarction. Sixty male CD-1 mice weighing
      approximately 40 g were used in the study. Forty mice were subjected to left
      coronary artery ligation and randomized to receive AdCT-1 vector (treated group)
      or AdLacZ vector (control group) treatment, with 20 mice for each group. AdCT-1
      or AdLacZ vector was directly injected into the border zone of the ischemic
      myocardium at six sites, 10 min after ligation (10 microl/site, 2.5 x 10(6)
      PFU/100 microl). Twenty mice undergoing thoracotomy and injection of an equal
      volume of phosphate-buffered saline solution but not coronary ligation served as
      sham group. Hemodynamics, histopathology and cardiomyocyte apoptosis were
      detected at 2 weeks after injection. Four animals in sham, nine in control, and
      six in treated groups died during the experiment. The remaining 41 mice were
      included in the study. Mean arterial pressure, left ventricular systolic
      pressure, and the maximum rate of left ventricular pressure rise or fall were
      significantly higher in treated group than in control group (P < 0.01 for all),
      whereas left ventricular end-diastolic pressure, infarct size, the ratio of right
      ventricle or lung weight to body weight, and apoptotic index were significantly
      lower in treated group than in control group (P < 0.01 for all). The caspase-3
      activation and mitochondrial cytochrome c release were also lower in treated
      group than in control group (P < 0.01 for each). AdCT-1 injection significantly
      inhibited Fas, Bax and p53, and increased CT-1 and Bcl-2 expression in
      myocardium. Our results suggest that AdCT-1 vector can be effectively transfected
      and continued to express bioactive CT-1 protein in myocardium. CT-1 plays an
      important cardioprotective effect on myocardial damage in the murine model of
      myocardial infarction.

PMID- 18092237
TI  - Introduction to the special issue on psychiatric prevention.

PMID- 18092238
TI  - The prevention of conduct problems.
AB  - This article summarizes the current knowledge base in the prevention of childhood
      conduct problems. First, childhood conduct problems and comorbid conditions are
      described, followed by a review of risk factors that have been found to
      contribute to the development of conduct problems. Risk factors include both
      internal child characteristics such as temperament and genetic/neurobiological
      influences, and external factors such as family, peer, and neighborhood
      influences. Finally, descriptions are provided for several intervention programs
      that have demonstrated empirical support in the prevention of youth conduct
      problems.

PMID- 18092239
TI  - School-based programmes to prevent alcohol, tobacco and other drug use.
AB  - Substance use and abuse are important public health problems in the USA and
      throughout the world. In many developed countries, the initial stages of
      substance use typically include experimentation with alcohol, tobacco, or
      marijuana with one's peer group during adolescence. While there have been gradual
      decreases in the use of these substances in recent years among youth in the USA
      and other countries, increases have been observed in the use and misuse of other
      substances, such as the misuse of prescription drugs and over-the-counter cough
      medications in the USA. From a developmental perspective, data shows that rates
      of alcohol, tobacco, marijuana, and other illicit drug use typically escalate
      during adolescence and peak during young adulthood, corresponding with the
      increased freedom and independence of this time of life. Substance use decreases
      for most young people as they take on adult responsibilities, although a
      proportion will continue or increase their use and develop substance use
      problems. Given what we know about the onset and progression of substance use,
      implementing preventive interventions during early adolescence is critical. Most
      drug prevention or education programmes take place in school settings. A variety
      of theory-based school-based drug prevention programmes have been developed and
      tested. The most effective programmes are delivered interactively and teach
      skills to help young people refuse drug offers, resist pro-drug influences,
      correct misperceptions that drug use is normative, and enhance social and
      personal competence skills. A key challenge is to identify mechanisms for the
      wide dissemination of evidence-based drug preventive interventions and ways to
      train providers to implement programmes effectively and thoroughly.

PMID- 18092240
TI  - The role of randomized trials in testing interventions for the prevention of
      youth suicide.
AB  - Epidemiological considerations point to a small handful of prevention strategies
      that have the potential for dramatically reducing suicide rates. Nearly all of
      those prevention approaches involve population-based strategies to either find an
      increased number of individuals at high risk for suicide or to reduce the
      prevalence of risk factors in members of a population that, as a whole, has a
      relatively low rate of suicide. Few of these approaches have been evaluated in
      rigorous trials. We argue that there are rigorous randomized trial designs that
      are both feasible and ethical and can be used to test both programmes and
      implementation strategies for population-based suicide prevention. We review
      existing suicide prevention trials and introduce two new randomized trial designs
      that are likely to achieve sufficient statistical power. The 'dynamic wait-listed
      design' randomizes across different time periods and is now being used to test a
      gatekeeper training programme in 32 schools. It could also be used to examine
      suicide prevention programmes in rural areas. The multi-trial follow-up study
      builds on the large number of successful population-based preventive
      interventions aimed at reducing known risk factors for suicide in youths to see
      whether these also cause a reduction in rates of completed suicide.

PMID- 18092242
TI  - Prevention of anxiety disorders.
AB  - Anxiety disorders are very common and burdensome conditions with early onsets.
      Thus, there has recently been increasing interest in preventing these illnesses.
      In this article we review recent prevention studies targeting populations at
      varying levels of risk and conclude that prevention using cognitive-behavioural
      interventions is promising, though establishing longer-term effects and the cost
      effectiveness of such interventions are important next steps for the field. We
      discuss conceptual and practical issues with regard to prevention of anxiety
      disorders and note that theory-based models of prevention which are based on
      identified risk and protective factors, address the optimal timing of
      intervention delivery, and articulate specific mechanisms of action are greatly
      needed.

PMID- 18092243
TI  - Prevention of depression: the state of the science at the beginning of the 21st
      Century.
AB  - Major depression is one of the most prevalent mental disorders and the number one
      cause of disability worldwide. Once a person experiences a major depressive
      episode (MDE), the likelihood of recurrence is very high. The prevention of first
      onset, as well as the protection against recurrence after recovery, are therefore
      essential goals for the mental health field. By the end of the 20th century,
      however, most depression research efforts had focused on either acute or
      prophylactic treatment. In this article, we review USA and international studies
      that have attempted to reduce incidence of MDE, either 1) to prevent onset in
      populations of children and adults (including women during the postpartum period)
      not currently meeting diagnostic criteria for depression, or 2) to prevent a new
      episode in individuals who have recovered after treatment through protective, but
      not prophylactic interventions. We identified twelve randomized controlled trials
      focused on preventing the onset of major depression (both MDE and postpartum
      depression (PPD)), five randomized controlled trials focusing on preventing
      relapse, and no randomized controlled trials focused exclusively on preventing
      recurrent episodes through protective interventions. The review is limited in
      scope given that depression prevention trials focused on infants, young children,
      and older adults were not included in the review. The research to date suggests
      that the prevention of major depression is a feasible goal for the 21st century.
      If depression prevention interventions become a standard part of mental health
      services, unnecessary suffering due to depression will be greatly reduced. This
      review concludes with suggestions for the future direction of depression
      prevention research.

PMID- 18092241
TI  - The prevention of schizophrenia.
AB  - Preventive strategies can be divided into universal, selective and indicated
      prevention and early intervention. Universal interventions are directed to the
      general population. Selective approaches are targeted at people who have risk
      factors for an illness, but who do not show any current signs. Indicated
      approaches target high risk individuals with minimal signs or symptoms
      foreshadowing mental disorder, but who do not meet diagnostic levels at the
      current time. Early intervention involves treating those with already diagnosable
      disorder in a timely and optimal manner aiming to decrease the severity of the
      illness, and reduce secondary morbidity. Although universal and selective
      interventions are not yet viable strategies, indicated prevention and early
      intervention are now realistic possibilities in schizophrenia. Development of
      methods to identify those at risk of psychosis continues to evolve. Promising
      results in the prevention and delay of transition to psychotic disorder from high
      risk state have been found. Early intervention in schizophrenia, including
      promotion of early help-seeking, has been shown to reduce the duration of
      untreated psychosis, which is known to be associated with poor outcome in
      schizophrenia. Early intervention programmes which optimise the care of the first
      episode have been shown to produce better outcomes than routine management.

PMID- 18092244
TI  - Lead and cognitive function in adults: a questions and answers approach to a
      review of the evidence for cause, treatment, and prevention.
AB  - Lead has been extensively used worldwide in gasoline, consumer products,
      commercial applications, and industrial settings. Its use in gasoline and paint
      has been particularly hazardous to public health leading to widespread population
      exposure and substantial lifetime cumulative doses in most Americans over age 40
      years. Cumulative lead dose can be estimated by measuring the current
      concentration of lead in tibia bone by X-ray fluorescence. A growing literature
      has documented that tibia lead levels are associated with decrements in cognitive
      function and declines in cognitive function over time. Furthermore, there are
      several interesting lines of biochemical and epidemiological investigation that
      have demonstrated potential links of lead to neurodegenerative diseases. These
      studies support the inference that a proportion of what has been termed 'normal'
      age-related cognitive decline may, in fact, be due to exposure to neurotoxicants
      such as lead. Well-designed studies of cumulative lead dose and Alzheimer's
      disease risk should be conducted to follow-up on these leads. The strong and
      compelling body of literature on lead and cognitive dysfunction and decline also
      supports a need for intervention studies to prevent lead-related cognitive
      decline.

PMID- 18092245
TI  - Prevention of Alzheimer's disease.
AB  - The already considerable public health burden of Alzheimer's disease will likely
      worsen as populations around the world age. As a result, there is considerable
      motivation to develop effective strategies for preventing the disease. A wide
      variety of such strategies are under investigation and include pharmaceuticals,
      nutriceuticals, diet, physical activity and cognitive activity. We review here
      the most promising candidates and the epidemiologic evidence for their efficacy.
      Although none of these have yet to be definitively shown to prevent Alzheimer's
      disease, further research should help to clarify what role they may play in
      reducing the burden of this disease.

PMID- 18092246
TI  - Systemic type Epstein-Barr virus-related lymphoproliferative diseases in children
      and young adults: challenges for pediatric hemato-oncologists and infectious
      disease specialists.
AB  - Involvement of Epstein-Barr virus (EBV) has long been known in the development of
      various tumor-forming proliferating diseases, such as nasopharyngeal carcinoma in
      adults. However, in children and young adults more attention should be focused on
      systemic, severe type EBV-related diseases, such as fatal infectious
      mononucleosis, hemophagocytic syndrome, or chronic active EBV infection (CAEBV).
      These disorders show the typical clinical features of hemophagocytic
      lymphohistiocytosis (HLH). Although viral infectious diseases are mostly taken
      care of by infectious disease specialists, pediatric hemato-oncologists need to
      intervene in the treatment of this kind of disease because of their clonal and
      neoplastic disease characteristics and of their hematologically problematic,
      rapid, and life-threatening clinical courses.

PMID- 18092247
TI  - Hematopoietic cell transplantation: a curative option for sickle cell disease.
AB  - Sickle cell disease is associated with considerable morbidity and premature
      mortality. Hematopoietic cell transplantation offers the possibility of cure and
      is associated with excellent results in pediatric patients receiving stem cell
      transplantation from a matched sibling donor. Reduced intensity conditioning
      regimen have the potential to further reduce regimen related morbidity and
      mortality. Improved understanding of the natural history of complications such as
      stroke and pulmonary hypertension, effects of treatments, such as hydroxyurea and
      blood transfusions, as well as the impact of transplantation on organ damage are
      likely to influence the timing and indication of transplantation. Improvements in
      preparative regimen may enable the safe use of alternate source of stem cells
      such as unrelated matched donors and further improve the applicability and
      acceptability of this treatment.

PMID- 18092248
TI  - Low bone mass in children with malignant lymphoma.
AB  - The aim of this work was to study the effect of disease process on bone mass and
      calcium homeo-stasis in children with malignant lymphoma at diagnosis, 3 months
      after starting chemotherapy, and after 1 year. Evaluation of lumber vertebrae (L2
      L4) bone mineral density using dual-energy X-ray absorptiometry and calcium
      homeostasis parameters and bone turnover biochemical markers (serum osteocalcin
      and urinary deoxypyridinoline) had been assayed in twenty lymphoma patients at
      presentation and after treatment. Low bone mass for chronological age was
      observed in 4 patients (20%) at diagnosis and persisted after 3 months and 1
      year. Parathyroid hormone level demonstrated no differences between children with
      lymphoma at different stages of therapy and controls, while 25(OH) D(3) was
      significantly lower in lymphoma patients at different stages of therapy as
      compared to controls (p < .001). Osteocalcin was significantly lower in lymphoma
      patients at different stages of therapy. Deoxypyridinoline showed only
      significant higher values after 3 months of therapy compared to controls (p =
      .01). In conclusion, low bone mass was observed in children with lymphoma and is
      related to decreased osteoblastic activity and decreased mineralization of bone.

PMID- 18092249
TI  - Comparison of accelerated and rapid schedules for monovalent hepatitis B and
      combined hepatitis A/B vaccines in children with cancer.
AB  - The aim of this study was to determine the efficacy of immunization against
      hepatitis A and B infections with "rapid" or "accelerated" schedules in children
      with cancer receiving chemotherapy. Fifty-one children were recruited to receive
      either vaccination schedule, in the "rapid vaccination schedule"; hepatitis B
      (group I) or combined hepatitis A/B vaccines (group III) were administered at
      months 0, 1, 2, and 12; in the "accelerated vaccination schedule," hepatitis B
      (group II) or combined hepatitis A/B (group IV) vaccines were administered on
      days 0, 7, 21, and 365 intramuscularly. The seroconversion rates at months 1 and
      3 were 35.7 and 57.1% in group I and 25 and 18.8% in group II, respectively.
      Group I developed higher seroconversion rates at month 3. In group III the
      seroconversion rates for hepatitis B at months 1 and 3 were 54.5 and 60% and in
      group IV 50 and 70%, respectively. For hepatitis A, the seroconversion rates at
      months 1 and 3 were 81.8 and 90% in group III and 80 and 88.9% in group IV,
      respectively. The accelerated vaccination schedule seems to have no advantage in
      children receiving cancer chemotherapy except for high antibody levels at month
      1. In conclusion, the accelerated vaccination schedules are not good choices for
      cancer patients. The combined hepatitis A/B vaccine is more effective than
      monovalent vaccine in cancer patients, which probably can be explained by an
      adjuvant effect of the antigens. The seroconversion of hepatitis A by the
      combined hepatitis A/B vaccination is very good in cancer patients.

PMID- 18092250
TI  - Clinical outcome of febrile neutropenia in children with cancer using ceftazidime
      and aminoglycosides.
AB  - To determine treatment outcome using ceftazidime-aminoglycosides in febrile
      neutropenic children with cancer, the authors conducted a prospective cohort
      study in 216 episodes. Early and complete responses to antibiotics were 108/216
      (50.0%) and 133/216 (61.6%) episodes, respectively. Death, a modification of
      antibiotic(s), and resistance to ceftazidime were 2/118 (1.7%), 73/216 (33.8%),
      and 4/216 (1.9%) episodes, respectively. Primary bacteremia and emerging
      bacteremia during treatment were 20/216 (9.3%) and 5/216 (2.3%) episodes.
      Ceftazidime-aminoglycosides was found to be a reasonable initial treatment of
      febrile neutropenia in the authors' institution. Imipenem is considered in
      patients who have clinical sepsis and who fail to respond to initial treatment.

PMID- 18092251
TI  - Specific viruses were not detected in Guthrie cards from children who later
      developed leukemia.
AB  - There are hypotheses concerning infectious mechanism in the development of acute
      lymphoblastic leukemia (ALL). The first genetic event often happens in utero,
      based on studies from Guthrie cards. The authors have summarized the results from
      their studies concerning infectious mechanism. Presence of human polyomaviruses,
      parvovirus, HHV-6, EBV, and CMV were investigated by PCR from Guthrie cards from
      children who later developed ALL and healthy controls. Neither of these viruses
      were detected from patients nor from controls. The results do not support that
      these viruses have contributed to the development of a substantial part of the
      ALL cases in Swedish children.

PMID- 18092252
TI  - Veno-occlusive disease in a child with rhabdomyosarcoma after conventional
      chemotherapy: report of a case and review of the literature.
AB  - Although veno-occlusive disease of the liver is a well-known complication of high
      dose chemotherapy and bone marrow transplantation, it has rarely been observed in
      children who receive conventional chemotherapy. Most cases in the literature
      consists of children with Wilms tumor. It has been very uncommon in
      rhabdomyosarcoma patients until recently, although they commonly receive similar
      anticancer agents. Here the authors report a 2-year-old boy with rhabdomyosarcoma
      who developed veno-occlusive disease while receiving VAC (vincristine,
      actinomycin D, cyclophosphamide) chemotherapy regimen according to the IRS-IV
      protocol. The patient gradually recovered during 2 weeks with supportive
      treatment only.

PMID- 18092253
TI  - Tibial pseudotumor in a child with hemophilia.
AB  - Hemophilic pseudotumor is an uncommon complication seen in approximately 1-2% of
      patients with severe hemophilia. Hemophilic pseudotumors are distinguished into
      two subdivisions based on location, proximal or distal. Plain x-rays and CT are
      useful in diagnosis, but MR imaging is the diagnostic test of choice because of
      its sensitivity to the various blood products. The choice of therapy depends on
      many parameters, such as the size of the tumor, the age of the patient, and the
      relation with underlying organs. In most cases of asymptomatic hemophilic
      pseudotumor, conservative treatment with administration of missing factor as well
      as immobilization is recommended. The authors describe a 13-year-old boy with
      severe hemophilia A, who presented with a tibial pseudotumor a few months after
      an injury. He was conservatively treated for a long period, with daily
      administration of recombinant factor VIII. His clinical condition improved
      shortly after therapy induction, but radiological improvement has been moderate.
      Case history, imaging findings, and therapeutic options are discussed.

PMID- 18092254
TI  - Successful combination of antifungal agents and surgical resection for pulmonary
      aspergillosis in a child with Hodgkin disease: review of the literature.
AB  - The authors report on a 14-year-old adolescent boy suffering of Hodgkin disease
      in remission, who developed autoimmune anemia and thrombopenia. He was treated
      with high-dose steroids and he developed serious invasive lung aspergillosis,
      which was treated with antifungal agents and surgical intervention. Children
      suffering from cancer are prone to develop systemic fungal infections secondary
      to the severe immunosuppression caused by the disease itself and the
      antineoplastic therapy. Intravenous antifungal medications and, when feasible,
      surgery are used for treatment of pulmonary aspergillosis. Factors related to
      better outcome are early diagnosis, remission of underlying disease, aggressive
      antifungal therapy, and recovery from neutropenia.

PMID- 18092255
TI  - Rhabdomyosarcoma of the uvula.

PMID- 18092256
TI  - Treating children with chronic hepatitis C after malignancy in a single center.

PMID- 18092257
TI  - Anticoagulant system activity in splenectomized versus non-splenectomized Iranian
      patients with beta-thalassemia major.

PMID- 18092260
TI  - The number needed to treat for adalimumab, etanercept, and infliximab based on
      ACR50 response in three randomized controlled trials on established rheumatoid
      arthritis: a systematic literature review.
AB  - OBJECTIVE: To compare the efficacy of adalimumab, etanercept, and infliximab in
      patients with established rheumatoid arthritis (RA) taking concomitant
      methotrexate (MTX) by calculating the number needed to treat (NNT) using three
      different methods. METHODS: A systematic literature search of the Cochrane
      Library, MEDLINE, and EMBASE was conducted from inception to 30 June 2006. Two
      pairs of investigators, a Danish and a Swedish pair, independently conducted a
      structured literature review. The reviewers selected any published randomized,
      double-blind, MTX controlled study of adalimumab, etanercept, and infliximab,
      presenting the American College of Rheumatology 50% response (ACR50) after 12
      months in RA patients with a mean disease duration of at least 5 years. The two
      review groups independently extracted the estimates necessary to calculate the
      NNT. RESULTS: The reviewers consistently selected the same three randomized,
      controlled trials (RCTs), one for each of the drugs, and extracted equal data for
      the number of patients completing the 12-month intervention, and the
      corresponding number of ACR50 responding patients after therapy. Some baseline
      differences were noted: patients in the etanercept trial had a shorter disease
      duration and did not receive MTX prior to inclusion; patients in the adalimumab
      study had lower Health Assessment Questionnaire (HAQ) scores. The calculated NNTs
      varied slightly depending on the method used. The fully adjusted NNTs (95%
      confidence intervals) for adalimumab, etanercept, infliximab standard dosage and
      infliximab double dosage were 4 (3-6), 4 (3-6), 8 (4-66), and 4 (3-11) patients,
      respectively. CONCLUSION: This study indicates equal efficacy of the three anti
      tumour necrosis factor (TNF) therapies.

PMID- 18092261
TI  - Infliximab dosage and infusion frequency in clinical practice: experiences in the
      Stockholm biologics registry STURE.
AB  - OBJECTIVE: To characterize dosages and frequencies of infliximab in a publicly
      financed health-care system without administrative restrictions on the use of
      biologics. METHODS: Data from the Stockholm TNFalpha follow-up registry (STURE)
      were used. Dosages and frequencies of infliximab were adjusted when clinically
      indicated. Kaplan-Meier survival function was calculated for maintenance of
      initial infliximab dosage, initial frequency, and both combined; the influence of
      baseline characteristics on the adjustments and the effects of these adjustments
      on clinical outcomes were analysed. All analyses were for patients who continued
      on therapy only. RESULTS: The 1-year survival on initial infliximab frequency was
      96.3+/-1.8%, on initial infliximab dose 70.5+/-4.3%, and on the two combined
      68.7+/-4.3% (cumulative survival estimate +/- SE). At 2 years, the corresponding
      values were 88.1+/-3.4%, 53.4+/-5.1%, and 50.3+/-5.1%, and after 3 years 77.4+/
      4.9%, 45.9+/-5.4%, and 41.5+/-5.3%. A higher number of prior disease-modifying
      anti-rheumatic drugs (DMARDs), use of glucocorticoids, and lower baseline swollen
      joints counts (SJCs) predicted greater likelihood of later adjustments. Efficacy
      of dosage increases was modest, as reported previously, while frequency increases
      appeared more efficacious. CONCLUSION: Infliximab dosages and dosing frequencies
      are increased frequently in clinical practice: after 3 years, only 42% of
      patients continued on the original schedule. While frequency increases appear to
      result in better effect persistence between infusions, the gains from dosage
      increases are small and may not be better than chance. These data suggest that
      the total amounts of infliximab needed to obtain satisfactory disease control are
      greater than the amounts suggested by the original dosing recommendations, and
      may have bearing on pharmaco-economic issues pertaining to treatment with
      infliximab and other therapeutic agents.

PMID- 18092263
TI  - Accumulation of FoxP3-expressing CD4+CD25+ T cells with distinct chemokine
      receptors in synovial fluid of patients with active rheumatoid arthritis.
AB  - OBJECTIVE: To explore the presence and characteristics of FoxP3-expressing
      CD4+CD25+ regulatory T cells in synovial fluid (SF) of patients with active
      rheumatoid arthritis (RA). METHODS: The frequency and chemokine receptors
      expression profile of FoxP3-expressing CD4+CD25+ regulatory T cells in SF and
      peripheral blood (PB) from RA patients and PB from healthy controls were
      investigated by flow cytometry using three- or four-colour intracellular
      staining. RESULTS: The frequency of CD4+CD25+ FoxP3+ T cells was increased
      significantly in SF compared with paired PB from RA patients and PB from healthy
      controls (p<0.05). However, the frequency in PB from RA patients was
      significantly lower than in PB from healthy controls (p<0.05). Notably,
      CD4+CD25+FoxP3+ T cells in SF expressed increased levels of inflammation-related
      trafficking chemokine receptors, such as CCR4, CCR5, and CXCR4. CONCLUSION: There
      is an accumulation of FoxP3-expressing regulatory T cells in RA SF, and such
      recruitment may be dependent on the distinct chemokine receptors expressed on
      regulatory T cells.

PMID- 18092262
TI  - Intensifying treatment of rheumatoid arthritis with combinations of traditional
      disease-modifying anti-rheumatic drugs among patients with persistent disease did
      not reduce the need for large joint surgery.
AB  - OBJECTIVE: To analyse how treatment of patients with rheumatoid arthritis (RA)
      influenced the duration of the disease before the first large joint surgery,
      arthrodesis or arthroplasty, in two patient cohorts 10 years apart. METHODS: Data
      on patients with RA having an arthrodesis or arthroplasty of a large joint from
      1990 to 1992 and from 2000 to 2002 and the type of medication used among all
      patients with RA in 1988-2002 were extracted from the data set of Kuopio
      University Hospital. RESULTS: The median duration of the disease before the
      decision of arthrodesis was 6.0 (range 1-25) years in 1990-92 and 9.0 (1-31)
      years (p = 0.307) in 2000-02, and of arthroplasty 10.5 (0-27) and 12.5 (0-59)
      years (p = 0.820), respectively. A significant shift from only symptomatic
      treatment or one disease-modifying anti-rheumatic drug (DMARD) to the more common
      use of immunosuppressants and/or combinations of at least two DMARDs occurred
      between 1992 and 2002. CONCLUSIONS: Treatment of RA at diagnosis and during the
      first years after diagnosis was traditional. Intensifying treatment later in the
      disease course did not reduce the need for large joint surgery as it occurred in
      the same time range in both cohorts.

PMID- 18092264
TI  - The effect of endostatin evaluated in an experimental animal model of collagen
      induced arthritis.
AB  - OBJECTIVE: To investigate the arthritis-inhibiting effect of endostatin, a potent
      angiogenesis inhibitor, on type II collagen-induced arthritis (CIA). METHODS: In
      an experimental system of prophylactic administration, endostatin was
      administered once daily at 1 mg/kg/day or 10 mg/kg/day for 2 weeks from before
      the onset of arthritis. In the experimental system of therapeutic administration,
      mice with an arthritis score of 1 to 3 were administered endostatin once daily at
      10 mg/kg. In the experimental system of continuous administration, endostatin was
      administered using an osmotic pump capable of continuously administering a
      calculated dose of 1 mg/kg/day for 2 weeks. RESULTS: Arthritis scores were lower
      in a dose-dependent manner in the prophylactic administration group than in the
      control group. Arthritis scores were lower in the therapeutic administration
      group than in the control group. Compared with the once-daily dosage regimen, the
      administration of endostatin by an osmotic pump achieved a similar arthritis
      inhibiting effect at one-tenth of the dose. CONCLUSION: Both prophylactic and
      therapeutic administration of endostatin inhibited type II CIA in mice. The
      administration method using an osmotic pump is useful.

PMID- 18092265
TI  - Lymphocytotoxic antibodies in systemic lupus erythematosus are associated with
      disease activity irrespective of the presence of neuropsychiatric manifestations.
AB  - OBJECTIVES: To evaluate the association of the presence of lymphocytotoxic, anti
      beta2-glycoprotein I (anti-beta2-GPI) and anti-ribosomal P (anti-P) antibodies in
      patients with systemic lupus erythematosus (SLE), presenting or not
      neuropsychiatric (NP) manifestations, stratified according to the activity of the
      disease. METHODS: A total of 138 patients with SLE (59 with active NPSLE, 49 with
      active non-NPSLE, and 30 with inactive disease) and 57 healthy controls were
      studied. Disease activity was assessed by the SLE Disease Activity Index
      (SLEDAI). The presence of lymphocytotoxic antibodies was assessed using a
      complement-dependent lymphocytotoxicity assay. The presence of anti-beta2-GPI and
      anti-P antibodies was detected by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: Lymphocytotoxic antibodies were detected primarily in patients with
      active disease, that is in 35 out of 59 (59.3%) NPSLE and 23 out of 49 (46.9%)
      non-NPSLE patients, whereas only four out of 30 (13.3%) inactive SLE patients and
      none of the healthy controls exhibited the autoantibody. The frequency of
      lymphocytotoxic antibodies in active SLE patients, considered as a whole or
      stratified into NPSLE or non-NPSLE, was significantly increased in relation to
      inactive SLE patients (p<0.001 for each comparison). No significant difference
      was observed when comparing active NPSLE with non-NPSLE patients. No associations
      were observed between the presence of anti-beta2-GPI or anti-P antibodies and the
      activity of SLE or the presence of lymphocytotoxic antibodies. CONCLUSIONS:
      Lymphocytotoxic antibodies occurred more frequently in patients with active SLE
      than in patients with inactive disease, irrespective of the presence of NP
      manifestations, a finding that is similar to classical biomarkers of lupus
      activity (anti-dsDNA and complement). These results indicate that the assessment
      of the presence of lymphocytotoxic antibodies may be an additional useful tool
      for the evaluation of SLE activity.

PMID- 18092266
TI  - Increased titres of anti-nuclear antibodies do not predict the development of
      associated disease in the absence of initial suggestive signs and symptoms.
AB  - OBJECTIVE: To determine whether patients with elevated anti-nuclear antibodies
      (ANA), absent extractable nuclear antigen (ENA) reactivity, and no definite
      associated disease develop an ANA-associated disease (AAD). METHODS: Patients
      with ANA titres of at least 1:320 and no ENA reactivity were identified by
      searching the database of our laboratory serving a tertiary care university
      hospital between 1998 and 2002. Medical records of this index time point were
      reviewed to exclude patients with active AAD at screening. Case patients were
      contacted by questionnaire between 2004 and 2005 and invited for a clinical visit
      to ascertain the individual disease status. RESULTS: Seventy-six patients were
      evaluated after a median follow-up of 32 months. An AAD was diagnosed in eight
      patients: connective tissue disease (CTD) in three, autoimmune hepatitis in two,
      rheumatoid arthritis in one, encephalomyelitis disseminate in one, and lymphoma
      in one. The only predictive factor associated with the development of AAD was the
      suspicion of an autoimmune disease by the treating physician at the initial
      evaluation. In the absence of initial suspicion for an autoimmune disease, only
      two out of 54 patients developed AAD, whereas six out of 22 patients with initial
      disease suspicion developed a defined AAD. CONCLUSION: In the absence of a
      clinical suspicion, elevated ANA titres have a low positive predictive value of
      4% for developing AAD for the upcoming 3 years.

PMID- 18092267
TI  - Simple counting of nailfold capillary density in suspected systemic sclerosis - 9
      years' experience.
AB  - OBJECTIVES: Capillary damage is a characteristic feature of systemic sclerosis
      (SSc). This work aimed to explore the potential clinical value of simple
      microscopic counting of capillary density. METHODS: In 325 patients admitted
      because of a clinical suspicion of SSc and in 80 healthy controls, nailfold
      capillary microscopy (NCM) was performed using a stereo-zoom microscope in 20 x
      magnification and with a transparent ruler in one of the eyepieces. Capillaries
      were counted within 3 mm in the centre of the nailfold in eight fingers. RESULTS:
      Capillary density (loops/mm) was decreased in patients with diffuse cutaneous SSc
      [median 4.7 (range 2.2-7.3)], limited cutaneous SSc [4.9 (2.0-7.3)], earlySSc
      [4.7 (2.8-7.3)], and preSSc [5.9 (4.3-8.2)] compared to healthy controls [7.2
      (5.8-9.0)]. Patients with morphea and with primary Raynaud's phenomenon had
      normal numbers of capillaries [7.0 (6.2-7.2) and 7.0 (5.3-8.7), respectively]. In
      only 21/325 (6%) patients was it not possible to count the capillaries because of
      insufficient transparency of the skin. There was no discrepancy in capillary
      density based on counts of two or eight fingers. When 43 patients were reassessed
      after 1 to 4 years, there was no difference between the two assessments.
      CONCLUSION: Determination of capillary density by direct microscopy counts, a
      simple, inexpensive and rapid method, helps to identify patients with SSc, early
      in the disease course and in patients with very limited skin involvement.

PMID- 18092268
TI  - Reduced exercise capacity in systemic sclerosis patients without pulmonary
      involvement.
AB  - OBJECTIVE: To evaluate the exercise capacity of women with systemic sclerosis
      (SSc) without pulmonary involvement using a cardiopulmonary stress test. METHODS:
      Thirteen consecutive female SSc patients [mean age 40.8+/-14 years, mean body
      mass index (BMI) 25.5+/-3.7 kg/m2] without pulmonary and cardiac involvement and
      13 healthy sedentary female controls (mean age 41.6+/-9.1 years, mean BMI 23.7+/
      3.8 kg/m2) matched by age and BMI underwent a maximum cardiopulmonary stress test
      (Bruce protocol). The following parameters were analysed: peak oxygen uptake
      (VO2peak), anaerobic threshold (AT), respiratory compensation point (RCP) and
      metabolic equivalent (MET) of the VO2peak. Comparisons between groups were
      analysed using the Student t-test. RESULTS: Forced vital capacity (FVC; 92.2+/
      14.2% predicted) and carbon monoxide diffusion lung capacity (DL CO; 85.8+/-5.8%
      predicted) were within the normal range in SSc patients. VO2peak of SSc patients
      was significantly reduced in comparison to the control group (19.8+/-4.6 vs.
      23.7+/-4.5 mL/kg/min, p = 0.04). SSc patients also had a significant reduction in
      MET at peak exercise (5.6+/-1.3 vs. 6.7+/-1.3 MET, p = 0.04) and a significant
      shorter time interval between AT and RCP compared to the control group (112.6+/
      95.6 vs. 164.0+/-65.3 s, p = 0.03). CONCLUSION: SSc patients without pulmonary
      impairment have reduced exercise capacity. Abnormal vascular response to exercise
      may account for this finding, as the vascular system is one of the major target
      organs in this pathological condition.

PMID- 18092269
TI  - Relapsing polychondritis in North India: a report of 10 patients.
AB  - OBJECTIVE: Relapsing polychondritis (RP) is a rare autoimmune disorder
      characterized by recurrent episodes of inflammation and destruction of
      cartilaginous tissues. We describe the outcome of 10 patients followed up at the
      Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh,
      over the past 10 years. METHODS: All the patients fulfilling the diagnostic
      criteria suggested by McAdam et al (Medicine (Baltimore) 1976;55:193-215) and
      modified by Damiani and Levine (Laryngoscope 1979;89;929-46) were included in the
      study. Detailed clinical features, investigations, treatment given, and outcome
      were recorded on file. RESULTS: Six women and four men, mean age 48.1 years
      (range 26-65 years), met the criteria for diagnosis. The mean duration of
      symptoms, before diagnosis, was 27 months (range 1-72 months). Clinical features
      included auricular chondritis (100%), arthritis (80%), fever (50%),
      constitutional symptoms (50%), eye involvement (50%), hearing loss (40%),
      collapsed bridge of nose (30%), laryngotracheal involvement (20%), aortic
      dilatation (10%), and nephrotic syndrome (10%). Two patients had the MAGIC (mouth
      and genital ulcers with inflamed cartilage) syndrome. The number of episodes of
      cartilaginous inflammation varied from one to eight. Treatment included oral
      prednisolone (n = 9), intermittent 'pulse' cyclophosphamide (n = 2), and
      azathioprine (n = 2). One patient required tracheostomy and died later. The
      others are doing well. Mean duration of follow-up was 35.5 months (range 1-79
      months). CONCLUSIONS: The diagnosis of this potentially lethal condition is
      frequently delayed. Our series suggests that clinical manifestations of RP are
      similar in Caucasian, Oriental, and Asian populations. Laryngotracheal
      involvement was seen less frequently in our patients.

PMID- 18092270
TI  - Relative bone mineral density measured by metacarpal index (MCI) and chronic
      spinal syndromes: an epidemiological study.
AB  - OBJECTIVES: The results of previous studies on the association between bone
      mineral density (BMD) and chronic spinal syndromes have been contradictory.
      Therefore, we studied relative BMD measured by the metacarpal index (MCI) and its
      associations with chronic neck and low-back syndromes and diffuse idiopathic
      skeletal hyperostosis (DISH). METHODS: A population sample of 8000 Finns aged 30
      years and over was invited to a comprehensive health examination in 1978-1980;
      90% complied. In the clinical phase, a trained physician diagnosed chronic neck
      and low-back syndromes. Hand and chest radiographs were taken from 3568
      participants to determine the MCI and to diagnose DISH. Of these, 340 subjects
      were re-examined clinically in 2000. RESULTS: After adjusting for potential
      confounding factors, a high MCI showed a significant cross-sectional association
      with chronic neck syndrome and DISH. The odds ratio (OR) per increment of one
      standard deviation (0.1) of MCI for chronic neck syndrome was 1.33 [95%
      confidence interval (CI) 1.21-1.47] and for DISH 1.29 (95% CI 1.04-1.60). No
      association was found between MCI and chronic low-back syndrome. In the follow-up
      setting, however, baseline MCI did not predict the incidence of chronic neck or
      low-back syndromes. CONCLUSIONS: Relative BMD is directly proportional to the
      prevalence of chronic neck syndrome. Further studies are needed to clarify the
      mechanisms of the association. The close association found between high relative
      BMD and DISH suggests a joint metabolic factor, which needs to be studied further
      to determine its effects on bones and intervertebral discs.

PMID- 18092271
TI  - Urinary markers of altered collagen metabolism in fibromyalgia patients.
AB  - OBJECTIVE: To assess the metabolism of collagen in fibromyalgia (FM) patients,
      and to compare the occurrence of collagen metabolism markers to the severity of
      FM symptoms. METHODS: Morning urine was collected from 27 FM women fulfilling the
      American College of Rheumatology (ACR) criteria for FM, and from seven controls.
      FM patients completed the Fibromyalgia Impact Questionnaire (FIQ). Bone mineral
      density (BMD), isokinetic muscle strength in knee and elbow, and hand-grip
      strength were measured. Urinary concentrations of collagen type I cross-linked C
      telopeptide (CTX-I) and collagen type II cross-linked C-telopeptide (CTX-II) were
      determined by enzyme-linked immunosorbent assay (ELISA). Pyridinoline (Pyd) and
      deoxypyridinoline (Dpd) were determined by liquid chromatography, and
      hydroxyproline (Hyp) by spectrophotometry. All concentration data were normalized
      to creatinine. RESULTS: Mean values in the FM group and the control group,
      respectively, were: urinary CTX-I 246.8 and 337.5 microg/mmol (p = 0.060); CTX-II
      110.4 and 185.1 ng/mmol (p = 0.035); Pyd 56.1 and 52.3 nmol/mmol (NS); Dpd 15.1
      and 14.0 nmol/mmol (NS); Pyd : Dpd ratio 4.05 and 3.96 (NS); Hyp 26.1 and 21.1
      micromol/mmol (NS). Significant inverse correlations were seen between CTX-I and
      the intensity of fatigue, and between CTX-II and anxiety. An inverse correlation
      between CTX-I and muscle strength was apparent, but relied on extreme values from
      one patient, and no significant correlation was found between CTX-I or CTX-II and
      tender points or BMD in the FM group. CONCLUSIONS: Low urinary concentrations of
      CTX-II and CTX-I and normal levels of Pyd and Dpd were found in FM, but their
      relationship to the intensity of FM symptoms was unclear.

PMID- 18092272
TI  - Erythroleukaemia complicating ANA-negative systemic lupus erythematosus.

PMID- 18092273
TI  - Spurious thyroid function tests in systemic lupus erythematosus.

PMID- 18092274
TI  - Antiphospholipid antibodies in children with Henoch-Schonlein purpura: a
      prospective study from North India.

PMID- 18092275
TI  - Severe polymyositis and flare in autoimmunity following treatment with adalimumab
      in a patient with overlapping features of polyarthritis and scleroderma.

PMID- 18092276
TI  - A case of recurrent abdominal bleeding due to polyarteritis nodosa despite
      immunosuppressive therapy.

PMID- 18092277
TI  - Influence of acute physical activity immediately before ultrasonographic
      measurement of Achilles tendon thickness.

PMID- 18092278
TI  - [Preoperative imaging in 78 living kidney donors using CE-MRA and DSA].
AB  - PURPOSE: To evaluate contrast-enhanced 3D magnetic resonance angiography (CE-MRA)
      and digital subtraction angiography (DSA) in comparison with the intraoperative
      findings in living kidney donors. MATERIALS AND METHODS: A total of 156 kidneys
      in 78 potential kidney donors were prospectively examined using CE-MRA (0.2 mmol
      Gd/kg, voxel size 1.3 x 0.8 x 2.0) and DSA. Two experienced radiologists assessed
      the images in consensus regarding the renal vascular anatomy and variants. The
      results for the 67 candidates accepted for donation were compared to the
      intraoperative findings. In the other kidneys not accepted for donor nephrectomy,
      MRA and DSA were compared with each other. RESULTS: Nineteen arterial variants
      were identified intraoperatively, of which 11 (58%) were also detected by
      preoperative CE-MRA and 10 (53%) by preoperative DSA. Of the 10 venous variants
      found intraoperatively, CE-MRA detected 8 (80%) and DSA 3 (30%). The agreement
      (kappa test) between MRI and DSA for all 156 evaluated kidneys was 0.7 for
      arterial variants (McNemar p=0.12) and 0.3 for venous variants (McNemar p=0.01).
      The preoperative choice of kidney (right or left) made on the basis of the renal
      vascular anatomy seen on CE-MRA and DSA differed in 22% of the 78 potential
      donors (McNemar p=0.3). CONCLUSION: Our results in a large group of potential
      living kidney donors suggest that CE-MRA and DSA are comparable for detecting
      arterial renal variants while CE-MRA is superior for identifying venous variants.
      The preoperative choice of transplant kidney was not significantly influenced by
      the different results of CE-MRA and DSA.

PMID- 18092279
TI  - [Consensus meeting of course experts in breast diagnosis 5 May 2007 in Frankfurt
      am Main--topic: microcalcinosis]].

PMID- 18092280
TI  - [Attainment of generic therapy goals in a specialized group psychotherapy for
      phobic outpatients].
AB  - Individual therapy goals of psychotherapy patients either focus on symptom relief
      (disorder specific) or on improvements also in other functional areas (generic).
      The present study with 62 outpatients in a cognitive behavioral group
      psychotherapy (CBGT) investigated whether patients attain their disorder specific
      goals better than their generic therapy goals. Results indicated that patients
      reached disorder specific goals to a higher degree than the generic goals,
      although the group treatment specifically targeted the disorder specific goals.
      Implications of the results for the assessment and therapy of phobic patients are
      discussed.

PMID- 18092281
TI  - [Influence of rescue service personnel's shift work on psycho-physical
      parameters].
AB  - BACKGROUND: The aim of the investigation was to receive information about the
      interaction between psycho-physical parameters as a function of the strain by
      shift work for rescue service personnel. MATERIAL AND METHODS: We examined 26
      persons, who are active in the rescue service. The investigations always took
      place in the morning between 7.00 and 8.00 o'clock, either after 3 days off (n =
      26), after 3 night shifts (n = 14) or in the morning of the third day shift (n =
      14). The investigations included measurements of blood pressure, heart rate
      variability, and salivary cortisol. Additionally, standardized questionnaires
      (WHO-5, EBF 72/3) were used. RESULTS: A significant rise of the quotient LF/HF-
      as indicator for a sympathetic dominance--could be proven by means of a simple
      three minute arithmetic task at every investigation (after 3 days off from 0.81
      to 2.30; p < 0.001). By means of the EBF a clear impairment could be demonstrated
      after 3 night shifts. Fatigue and somatic complaints were the main outcomes. In
      our study a more impaired well-being was associated with a more pronounced
      decrease of salivary cortisol (r = 0.538; p < 0.05) as well as lower blood
      pressure values (r = 0.547; p < 0.05), and a lower LF/HF quotient (r = 0.836; p <
      0.01), indicating lower sympathetic and/or increased vagale activation, after
      three night shifts. CONCLUSIONS: After three night shifts a lower sympathetic
      activation seems to negatively affect the well-being. Due to the provable
      specific strain night- and shift-workers should be a priority target group for
      prevention and workplace health promotion.

PMID- 18092282
TI  - [Diagnostics of work motivation (DIAMO): optimization and construct validity].
AB  - SUBJECT: Faced with increasing cost pressure of the social insurance system the
      carriers of rehabilitation programs focus on the efficacy of their measures. The
      diagnostic instrument for work motivation (DIAMO) has been developed to assess
      the influence of job-related motivation on the rehabilitation outcome. METHOD:
      The inner structure of the instrument was validated and optimized in a cohort of
      medical rehabilitation patients (n = 422). Construct validity was further tested
      by using established instruments. RESULTS: Ten scales related to self-image,
      intention of action and goodness of fit show good psychometric qualities
      (Cronbachs alpha: 0.72 - 0.86). The constructs correlate moderately-to-strongly
      with personality-oriented scales while correlation with disease-related contents
      is low. CONCLUSIONS: The DIAMO is a generic and not disease oriented instrument.
      It would be expected to facilitate the development of vocational interventions to
      increase the rehabilitation outcome.

PMID- 18092283
TI  - [Evaluation of a new concept for diagnosing adjustment disorders in a
      psychosomatic setting].
AB  - OBJECTIVE: Diagnoses of adjustment disorders are frequent in clinical settings,
      although diagnostic criteria are not very reliable or valid. This has led to a
      neglection of this topic in research. This article presents and applies a new
      concept (Maercker et al., 2007) for diagnosing adjustment disorders. METHODS: 96
      patients of a psychosomatic policlinic were examined regarding their emotional
      well-being with a new questionnaire (Adjustment Disorder--New Module | ADNM).
      Furthermore, according to the new concept, adjustment disorders were assessed
      with a structured interview. Coping behaviour (CISS) as well as general self
      efficacy (SWE) in patients with scores within a normal range and patients with
      elevated scores in ADNM, respectively, were examined. The following statistical
      measures were used: cluster analysis, cross tables, non-metrical and metrical
      test procedures. RESULTS: The theory-guided evaluation of the ADNM questionnaire
      divided the whole sample into patients with elevated (49 %) and with normal (51
      %) scores. A cluster analysis of patients with elevated scores showed two groups,
      so that a total of three groups were compared: patients with scores in a normal
      range; patients with elevated scores and a low number of symptoms; patients with
      elevated scores and a high number of symptoms. Patients with elevated scores
      showed significantly more emotion-oriented coping strategies (t = - 6.338; p =
      0.000) and reported, referring to present stress, on being less able to cope with
      it (Z = - 4.445; p = 0.000). Patients with elevated scores and a high number of
      symptoms named more stress factors (Z = - 2.634; p = 0.008) and reported on being
      more impulsive and irritable (Z = - 3.406; p = 0.003). The comparison of the ADNM
      questionnaire and the clinical main diagnoses shows a separation between
      emotional and non-emotional disturbances according to ICD-10 (chi2(2, n = 96) =
      6.928; p = 0.031). DISCUSSION: The results show that the ADNM questionnaire
      according to the new diagnostic concept of adjustment disorders (Maercker et al.,
      2007) identifies patients who experience a high degree of stress caused by
      adverse life events of life conditions. The ADNM reliably differentiates non
      emotional from emotional ICD-10 diagnoses. Further studies should examine,
      whether the new concept as well as the questionnaire are able to assess
      adjustment disorders in a valid and reliable way.

PMID- 18092284
TI  - [Prevalence of mental disorders among college students at a German university].
AB  - BACKGROUND: Students are an important part of the general population of Germany,
      but only limited information exists about the prevalence of common psychological
      syndromes among them. OBJECTIVE: To provide prevalence rates for various
      psychological syndromes (affective, anxiety, somotoform, eating disorders, and
      alcohol associated problems) among German university students. METHODS: A campus
      wide survey including N = 1130 students at the University of Mannheim was
      conducted. Established assessment instruments were employed for this purpose: the
      German version of the Patient Health Questionnaire (PHQ), the German Version of
      the Whiteley-Index (WI), and the Chemical Odor Sensitivity Scale (COSS) to screen
      for idiopathic environmental intolerance (IEI). RESULTS: PHQ criteria for at
      least one psychological disorder (apart from the alcohol abuse/dependence
      syndrome) were met by 22.7% of the students, more frequently by women than men
      (OR = 1.8). The alcohol syndrome (30.2%) was most frequent and the only syndrome
      which was more frequent in men than in women. The next frequent syndrome was the
      somatoform syndrome (9.1%), followed by other depressive syndromes (8.1 %), IEI
      (7.2%), major depression (6.0%) and hypochondriasis (4.2%). The presence of
      hypochondriasis increased greatly the risk for co-morbid disorders. All syndromes
      -with the exception of the alcohol syndrome and the binge eating disorder--were
      accompanied by functional impairments. CONCLUSIONS: We consider these results
      rather alarming, as they indicate a considerable need for both preventive and
      curative interventions in German students. However, further epidemiological
      studies are needed to prove the generalizability of our findings and to examine
      functional interrelations among and the course of these psychological syndromes.

PMID- 18092285
TI  - CT and MRI examinations left behind in the radiology department.
AB  - PURPOSE: To retrospectively document the reported computerized tomography (CT)
      and magnetic resonance imaging (MRI) examinations that were left behind in our
      radiology department, to calculate their cost, and to determine possible sources
      of waste in order to draw attention to this subject. MATERIALS AND METHODS: The
      reported and billed CT and MRI examinations for 2003 that were not taken from the
      radiology department were documented, and the percentage they represented of all
      CT and MRI performed that year were determined. The total cost of the
      examinations, including contrast media, was calculated. RESULTS: In all, 200 CTs
      out of 4390 and 95 MRIs out of 7003 were left behind in the radiology department
      during 2003. Total cost of the examinations, including the contrast media, was
      31,320 YTL. CONCLUSION: The percentages of CT and MRI examinations left behind in
      the radiology department were evaluated in this preliminary report. Since we did
      not find any similar study in the literature, we could not comment on the limits
      of acceptability of the results; however, we think other radiology departments
      should determine the percentages CTs and MRIs that are left behind and take the
      necessary precautions to minimize waste and reduce expenses.

PMID- 18092286
TI  - Diffuse stylohyoid chain ossification.
AB  - Clinical symptoms of stylohyoid chain ossification vary from ear pain to
      dysphagia. It is usually diagnosed coincidentally. Localized ossification of the
      chain is common, whereas diffuse ossification is rare. Herein, a case with
      bilateral diffuse stylohyoid chain ossification diagnosed with computed
      tomography, which was performed in order to evaluate the patient's
      temporomandibular joint pain, a rare onset of this condition, is discussed.

PMID- 18092287
TI  - Lung parenchymal injury and its frequency in blunt thoracic trauma: the
      diagnostic value of chest radiography and thoracic CT.
AB  - PURPOSE: The aims of this study were to determine the value of chest radiography
      in diagnosing lung parenchymal injury in patients with thoracic trauma, and to
      evaluate the frequency of lung parenchymal injury by using thoracic computed
      tomography (CT). MATERIALS AND METHODS: Between January 2005 and June 2006, we
      retrospectively evaluated the anteroposterior chest radiographs and thoracic CTs
      of 60 patients that presented to our emergency department and were hospitalized
      due to multi-organ trauma. RESULTS: Chest radiography revealed parenchymal injury
      in 32 of the patients, while thoracic CT confirmed parenchymal injury in only 27
      of these 32 patients. Chest radiographs did not reveal any parenchymal injury in
      28 of the patients, whereas thoracic CT detected parenchymal injury in 12 of
      these 28 patients. Thoracic CT results were accepted as the gold standard in the
      evaluation of patients with chest trauma and showed that the sensitivity,
      specificity, positive predictive value, and negative predictive value of chest
      radiography in determining parenchymal injury were 69%, 76%, 84%, and 57%,
      respectively. In addition, thoracic CT revealed that 65% of the patients with
      blunt thoracic trauma suffered parenchymal injury. CONCLUSION: The sensitivity of
      anteroposterior chest radiography in identifying lung parenchymal injury was low,
      with a high false negative rate; therefore, we think that early evaluation with
      thoracic CT is extremely helpful in the diagnosis and treatment of patients with
      thoracic trauma, adding to the cooperative work that exists between radiologists
      and emergency physicians.

PMID- 18092288
TI  - Clinical outcome assessment in mammography: an audit of 7,506 screening and
      diagnostic mammography examinations.
AB  - PURPOSE: To perform an audit of our routine mammographic practice and to compare
      our results to performance benchmarks. MATERIALS AND METHODS: We analyzed the
      outcomes of 7,506 consecutive examinations performed in 1 year. Screening and
      diagnostic cases were evaluated separately and mammographic assessments were
      based on the Breast Imaging Reporting and Data System (BI-RADS) classification.
      RESULTS: In 6,858 (91%) screening and 648 (9%) diagnostic cases, outcomes varied
      substantially. The recall rate was 10.9%. Estimated sensitivity and specificity
      were similar (100% vs. 98% and 88% vs. 94%) in the screening and diagnostic
      groups. Positive predictive values (PPV1, PPV2, and PPV3) were higher in the
      diagnostic group compared to the screening group (64%, 65%, and 68% vs. 4.9%,
      33%, and 39%, respectively). Cancer outcomes in the screening and diagnostic
      groups were, respectively, as follows: cancer detection rate, 6.1 per thousand
      vs. 86.4 per thousand; mean invasive cancer size, 15.7 mm vs. 24.5 mm; minimal
      cancers, 38% vs. 19%; stage 0-1 cancers, 50% vs. 21%; and lymph node negativity,
      76% vs. 29%. CONCLUSION: The measures of our screening outcomes were concordant
      with the literature and the performance benchmarks for screening mammography;
      however, in our diagnostic group, the reasons for the higher PPV, higher cancer
      detection rate, and the diagnosis of cancer in a more advanced stage compared to
      the performance benchmarks should be investigated with more detailed periodic
      audits.

PMID- 18092289
TI  - Perforated ileal diverticulitis: CT findings.
AB  - Diverticulosis of the ileum is very uncommon. The differential diagnosis for any
      inflammatory process in the right lower quadrant of the abdomen includes
      appendicitis, Crohn's disease, and other infectious and inflammatory conditions
      of the terminal ileum and cecum. Diagnosis of small bowel diverticulitis is based
      on radiological findings, and computed tomography is the method of choice to
      demonstrate mural changes and the mesenteric extent of the inflammation.
      Preoperative knowledge of this condition may influence surgical and medical
      management.

PMID- 18092290
TI  - Solitary osteochondroma causing popliteal pseudoaneurysm that presented as a mass
      lesion.
AB  - Osteochondromas are the most frequently occurring bone tumors and can rarely lead
      to vascular complications. A 14-year-old boy with solitary exostosis of the right
      femur presented with a mass lesion at the posterior aspect of the thigh.
      Radiological studies demonstrated a popliteal artery pseudoaneurysm. In this case
      report, radiological findings of this lesion are reviewed.

PMID- 18092291
TI  - The dot-in-circle sign of mycetoma on MRI.
AB  - Mycetoma is a chronic granulomatous disease prevalent in tropical countries, but
      it also occurs in Europe and the United States. Early diagnosis is important as
      it has therapeutic implications. Although biopsy and microbiological culture
      provide the definitive diagnosis, these are difficult to achieve in many
      instances. The dot-in-circle sign is a recently proposed magnetic resonance
      imaging (MRI) sign of mycetoma, which is likely to be highly specific. We present
      a case of mycetoma of the thigh with characteristic MRI features. To the best of
      our knowledge, only 2 cases of mycetoma of the foot demonstrating this sign have
      been previously published.

PMID- 18092292
TI  - Ultrasonographic prenatal diagnosis of isolated acephaly.
AB  - First trimester obstetric ultrasonography of a 32-year old female patient
      revealed a 13-week-old (according to the length of the femur and abdominal
      circumference) intrauterine live pregnancy with the absence of the fetal head.
      Medical abortus was performed with the diagnosis of acephaly and final diagnosis
      was confirmed by pathological and radiological examinations. We present and
      discuss the possible etiopathologic mechanisms of an acephaly case, which is
      described as acardia-acephaly complex in the literature, and usually appears in
      cases of twin reversed arterial perfusion sequence, but has not been previously
      reported as an isolated finding.

PMID- 18092293
TI  - Risk factors for occurrence of local tumor progression after percutaneous
      radiofrequency ablation for lung neoplasms.
AB  - PURPOSE: To examine the characteristics of lung tumors for which radiofrequency
      (RF) ablation therapy is effective, and to determine what RF ablation parameters
      are effective for obtaining complete coagulation of the entire ablation zone with
      a single RF ablation session. MATERIALS AND METHODS: Computed tomography (CT)
      guided RF ablation of lung tumors was performed on 82 lesions in 34 patients
      between April 2003 and May 2005. Tumor characteristics and ablation parameters,
      including tumor size, location, and depth, and ablation duration, power deployed
      during ablation, and temperatures achieved were analyzed with regard to local
      tumor progression. RESULTS: In all, 103 RF ablation sessions were performed on 82
      tumors. As a procedure-related complication, pneumothorax occurred in 27
      procedures. During the mean follow-up period of 10 months (range, 6-28 months),
      local tumor progression occurred in 18 (22.0%) of the 82 ablated tumors (3 months
      after RF ablation in 10, 6 months after RF ablation in 5, 9 months after RF
      ablation in 1, and 12 months after RF ablation in 2). Mean local progression-free
      duration was 8.7 +/- 4.5 months (range, 3-28 months). The frequency of local
      tumor progression was significantly correlated with size, whereas other variables
      had no statistical association. In tumors with a diameter > or =2.5 cm, only the
      period of ablation during the initial session was significantly correlated with
      subsequent local tumor progression (P = 0.000002, chi-square test). CONCLUSION: A
      long duration of RF ablation is desirable for large lung tumors. The success of
      RF ablation is dependent upon tumor size. RF ablation treatment is most effective
      for lesions < 2.5 cm.

PMID- 18092294
TI  - Image-guided catheter drainage of infected pleural effusions.
AB  - PURPOSE: To evaluate the safety and efficacy of image-guided drainage of infected
      pleural effusions. MATERIALS AND METHODS: The clinical outcomes of 93 patients
      who underwent image-guided drainage of infected pleural effusions between 1998
      and 2003 were retrospectively analyzed. Among the 93 patients, 31 (33.3%) were
      younger than 16 years of age. In all, 129 catheters (8F-14F pigtail catheters)
      were placed under ultrasonography (US) or computed tomography guidance. In 27
      patients (29.0%) intracavitary fibrinolytic therapy with streptokinase was
      employed to improve drainage. The patients were followed up during daily rounds
      and, when drainage problems occurred, catheters were exchanged or repositioned.
      New catheters were placed for undrained loculations. RESULTS: The success,
      failure, and recurrence rates were 92.5% (86/93), 7.5% (7/93), and 6.4% (6/93),
      respectively. In the pediatric age group the success rate was significantly
      higher. Intracavitary fibrinolytic therapy significantly improved daily output,
      but did not significantly reduce drainage duration or hospital stay. There was no
      significant difference between the successful and failed treatment cases in terms
      of US findings, gross appearance, or culture positivity. The only major
      complication was anaphylactic reaction due to intracavitary instillation of
      streptokinase (n = 1, 1.1%). The 30-day mortality rate was 2%. CONCLUSION: Image
      guided catheter drainage of infected pleural collections is a safe and effective
      method. Addition of intracavitary fibrinolytic instillation improves drainage,
      but early intervention prior to collections becoming more complicated remains an
      important factor in determining prognosis. Non-loculated anechoic collections
      without septa have a high probability of favorable outcome.

PMID- 18092295
TI  - Is uterine artery embolization prior to myomectomy for giant fibroids helpful?
AB  - PURPOSE: To determine whether uterine artery embolization (UAE) prior to
      myomectomy is more effective than myomectomy alone. MATERIALS AND METHODS: The
      study included 15 consecutive infertile women with uterine fibroids > 10 cm
      (Group I) that underwent UAE with spherical particles using a microcatheter
      technique and a unilateral femoral approach between March 2005 and January 2007.
      The day after embolization all cases underwent myomectomy since the protocol for
      large fibroids in our hospital is myomectomy only. The control group was composed
      of 15 patients who underwent myomectomy only (Group II). Group II was established
      based on fibroid size (14 +/- 3 cm). Operating time, estimated blood loss and
      transfusion, complications, and hospital stay were calculated by retrospective
      chart reviews, and comparisons were made between the groups with Student's t
      test. RESULTS: Mean operating time was 138 min in Group I and 240 minutes in
      Group II (P < 0.01). Mean estimated blood loss was 250 ml in Group I and 690 ml
      in Group II (P < 0.01). There was no need for transfusion in Group I, while
      transfusion was needed in 2 cases (13%) in Group II. Mean hospital stay in Group
      I was 5 days versus 8 days in Group II. Complications, including subsequent
      hysterectomy, were seen in 2 cases and bowel-bladder injuries in 1 case in Group
      II (a total of 20%), while no complications were observed in Group I. One of the
      cases in Group I later conceived and gave birth to a healthy child. CONCLUSION:
      UAE prior to myomectomy is more effective than myomectomy alone.

PMID- 18092297
TI  - Enantioseparation of 2-aryl-1,3-dicarbonyl analogues by high performance liquid
      chromatography using polysaccharide type chiral stationary phase.
AB  - The HPLC chiral separation of 21 kinds of 2-aryl-1,3-dicarbonyl analogues was
      investigated in normal phase mode with amylose tris(3,5-dimethylphenylcarbamate),
      amylose tris((S)-1-phenylethylcarbamate), cellulose tris(3,5
      dimethylphenylcarbamate), and cellulose tris(4-methylbenzoate) chiral stationary
      phases, respectively. The whole set of 2-aryl-1,3-dicarbonyl analogues shows
      better enantioselectivity and enantioseparation on amylose tris(3,5
      dimethylphenyl carbamate) (Chiralpak AD-H). The temperature dependence of
      enantioselectivity was studied to improve the enantioseparation. In addition,
      efforts are made to relate analyte structure with the quality of the achieved
      chiral separation.

PMID- 18092296
TI  - Emergency embolization of a bleeding renal angiomyolipoma using polyvinyl alcohol
      particles.
AB  - Angiomyolipomas (AMLs) are hamartomatous lesions consisting of abnormal blood
      vessels, smooth muscle, and adipose tissue. Bilateral AMLs invariably point to a
      diagnosis of tuberous sclerosis complex (TSC). The risk of hemorrhage in AML is
      related to tumor size, growth of the tumor, hypervascularization, presence of
      aneurysms, and association with TSC. We report a case of a young male who
      presented with painless hematuria. He was diagnosed with bilateral renal AMLs on
      ultrasonography and computed tomography. The large bleeding lesions were
      identified by renal angiography and selectively embolized using polyvinyl alcohol
      particles. To the best of our knowledge, isolated use of polyvinyl alcohol
      particles has not been previously reported.

PMID- 18092298
TI  - Synthesis and characterization of novel chiral ionic liquids and investigation of
      their enantiomeric recognition properties.
AB  - We report the synthesis and characterization of amino acid ester based chiral
      ionic liquids, derived from L- and D-alanine tert butyl ester chloride. The
      synthesis was accomplished via an anion metathesis reaction between commercially
      available L- and D-alanine tert butyl ester chloride using a variety of
      counterions such as lithium bis (trifluoromethane) sulfonimide, silver nitrate,
      silver lactate, and silver tetrafluoroborate. Both enantiomeric forms were
      obtained as confirmed by bands of opposite sign in the circular dichroism
      spectra. The L- and D-alanine tert butyl ester bis (trifluoromethane) sulfonimide
      were obtained as liquids at room temperature and intriguingly exhibited the
      highest thermal stability (up to 263 degrees C). In addition, the ionic liquids
      demonstrated enantiomeric recognition ability as evidenced by splitting of
      racemic Mosher's sodium salt signal using a liquid state (19)F nuclear magnetic
      resonance (NMR) and fluorescence spectroscopy. The L- and D-alanine tert butyl
      ester chloride resulted in solid salts with nitrate, lactate, and
      tetrafluoroborate anions. This illustrates the previously observed tunability of
      ionic liquid synthesis, resulting in ionic liquids of varying properties as a
      function of varying the anion.

PMID- 18092299
TI  - The application of preparative batch HPLC, supercritical fluid chromatography,
      steady-state recycling, and simulated moving bed for the resolution of a racemic
      pharmaceutical intermediate.
AB  - This article discusses the chromatographic resolution of a racemic pharmaceutical
      intermediate. Preparative batch high performance liquid chromatography (HPLC),
      supercritical fluid chromatography (SFC), steady-state recycling (SSR), and
      simulated moving bed (SMB) were used to resolve a total of 12.2 kg of a racemic
      pharmaceutical intermediate. In this study, a first batch of 0.8 kg of racemate
      was separated on the preparative batch HPLC and SFC, and subsequently another 5.9
      kg of racemate was separated on the SSR. Lastly, a third batch of 5.5 kg was
      separated on the SMB. The separation conditions and results of these techniques
      are discussed. The productivities and solvent costs of SFC versus HPLC are
      compared. The productivities and solvent costs of SMB, SSR, and HPLC are also
      compared. The analytical method development and process optimization of these
      processes are also discussed in this article.

PMID- 18092300
TI  - Modulatory effect of chiral nonsteroidal anti-inflammatory drugs on apoptosis of
      human neutrophils.
AB  - Polymorphonuclear neutrophils (PMNs) are short-lived leukocytes that die by
      apoptosis. Although PMNs are crucial in the defense against infection, they have
      been implicated in the pathogenesis of tissue injury observed in inflammatory
      diseases. The induction or prevention of PMN apoptosis is currently discussed as
      a key event in the control of inflammation. Caspase-3 activation is the first
      step in the execution phase of apoptosis. In the study, effect of racemic
      mixtures and enantiomers of 2-arylpropionic acid derivatives: ketoprofen,
      flurbiprofen (FBP), and (+)-S-naproxen and 2-arylbutyric acid: indobufen on
      apoptosis activation via caspase-3 and phosphatidylserine (PS) translocation
      (annexin-V binding) in human neutrophils in vitro has been investigated. Caspase
      3 activation was detected by Western blotting, fluorometric assay of DEVD-AMC
      cleavage, and flow cytometry with carboxyfluorescein (FAM) labeled caspase
      inhibitor. PMNs were isolated and cultured up to 24 h. The chiral nonsteroidal
      anti-inflammatory drugs (NSAIDs) were found to modulate human PMN apoptosis in a
      dose- and time-dependent manner. The greater activation of caspase was found at
      75-150 microg/ml concentration of racemates as well enantiomers, especially for
      FBP, whereas NSAIDs at smaller quantities (15 microg/ml) were inactive. At
      concentration of 75 microg/ml, NSAIDs increased the rate of PS externalization in
      PMA-stimulated and non-stimulated neutrophils. Additionally, no cytotoxic effect
      of the NSAIDs was observed at concentration up to 75 microg/ml that induce
      apoptosis. Regulation of caspase activity by NSAIDs may represent a potent target
      to trigger apoptosis and resolve inflammatory disorders.

PMID- 18092301
TI  - Stereoselective degradation of benalaxyl in tomato, tobacco, sugar beet,
      capsicum, and soil.
AB  - The stereoselective degradation of the racemic benalaxyl in vegetables such as
      tomato, tobacco, sugar beet, capsicum, and the soil has been investigated. The
      two enantiomers of benalaxyl in the matrix were extracted by organic solvent and
      determined by validated chiral high-performance liquid chromatography with a
      cellulose-tris-(3, 5-dimethylphenylcarbamate)-based chiral column. Rac-benalaxyl
      was fortified into the soil and foliar applied to vegetables. The assay method
      was linear over a range of concentrations (0.5-50 microg ml(-1)) and the mean
      recoveries in all the samples were more than 70% for the two enantiomers. The
      limit of detection for both enantiomers was 0.05 microg g(-1). The results in
      soil showed that R-(-)-enantiomer dissipated faster than S-(+)-enantiomer and the
      stereoselectivity might be caused by microorganisms. In tomato, tobacco, sugar,
      beet, and capsicum plants, there was significantly stereoselective metabolism.
      The preferential absorption and degradation of S-(+)-enantiomer resulted an
      enrichment of the R-(-)-enantiomer residue in all the vegetables.

PMID- 18092302
TI  - Separation and aquatic toxicity of enantiomers of 1-(substituted
      phenoxyacetoxy)alkylphosphonate herbicides.
AB  - A series of organophosphorous compounds (OPs), 1-(substituted
      phenoxyacetoxy)alkylphosphonates containing a chiral carbon atom, show notable
      herbicidal activities. In this study, the enantioselective separation and
      biological toxicity of all these compounds were investigated. The
      enantioselective separation on the columns of Chiralpak AD, Chiralpak AS,
      Chiralcel OD, and Chiralcel OJ were compared under various chromatographic
      conditions. All the analytes investigated obtained baseline resolution (R(s) >
      1.5) on Chiralpak AD column, which showed best chiral separation capacity.
      Further investigation was carried out on Chiralpak AD to evaluate the influence
      of the mobile phase composition and column temperature. The effect of the
      structural features on discrimination was also examined. The resolved enantiomers
      were distinguished by their signs of circular dichroism. The acute aquatic
      toxicity of enantiomers and racemate to Daphnia magna (D. magna) were assessed.
      The in vivo assays showed that compound 3 was about 2-148.5 times more toxic than
      the other four analogues to D. magna. The racemates of compounds 3 and 5 showed
      intermediate toxicity compare to their enantiomers, while those of compounds 1,
      2, and 4 showed synergistic or antagonistic effect. These results suggest that
      the biological toxicity of chiral OPs to nontarget organisms is enantioselective
      and therefore should be evaluated with their pure enantiomers.

PMID- 18092305
TI  - Response to: Validation studies of the health improvement network (THIN) database
      for pharmacoepidemiology research by Lewis et al.

PMID- 18092306
TI  - The effect of carbonyl group in the asymmetry of 3,4JCH coupling constants in
      norbornanones.
AB  - A rationalization of the known difference between the 3,4JC4H1 and 3,4JC1H4
      couplings transmitted mainly through the 7-bridge in norbornanone is presented in
      terms of the effects of hyperconjugative interactions involving the carbonyl
      group. Theoretical and experimental studies of 3,4JCH couplings were carried out
      in 3-endo- and 3-exo-X-2-norbornanone derivatives (X = Cl, Br) and in exo- and
      endo-2-noborneol compounds. Hyperconjugative interactions were studied with the
      natural bond orbital (NBO) method. Hyperconjugative interactions involving the
      carbonyl pi*(C2=O) and sigma*(C2=O) antibonding orbitals produce a decrease of
      three-bond contribution to both 3,4JC4H1 and 3,4JC1H4 couplings. However, the
      latter antibonding orbital also undergoes a strong sigmaC3--C4 --> sigma*(C2=O)
      interaction, which defines an additional coupling pathway for 3,4JC4H1 but not
      for 3,4JC1H4. This pathway is similar to that known for homoallylic couplings,
      the only difference being the nature of the intermediate antibonding orbital;
      i.e. for 3,4JC4H1 it is of sigma*-type, while in homoallylic couplings it is of
      pi*-type.

PMID- 18092307
TI  - Controlling false discoveries in genetic studies.
AB  - A false discovery occurs when a researcher concludes that a marker is involved in
      the etiology of the disease whereas in reality it is not. In genetic studies the
      risk of false discoveries is very high because only few among the many markers
      that can be tested will have an effect on the disease. In this article, we argue
      that it may be best to use methods for controlling false discoveries that would
      introduce the same ratio of false discoveries divided by all rejected tests into
      the literature regardless of systematic differences between studies. After a
      brief discussion of traditional "multiple testing" methods, we show that methods
      that control the false discovery rate (FDR) may be more suitable to achieve this
      goal. These FDR methods are therefore discussed in more detail. Instead of merely
      testing for main effects, it may be important to search for gene
      environment/covariate interactions, gene-gene interactions or genetic variants
      affecting disease subtypes. In the second section, we point out the challenges
      involved in controlling false discoveries in such searches. The final section
      discusses the role of replication studies for eliminating false discoveries and
      the complexities associated with the definition of what constitutes a replication
      and the design of these studies.

PMID- 18092308
TI  - Cell-specific internalization study of an aptamer from whole cell selection.
AB  - Nucleic acid aptamers have been shown many unique applications as excellent
      probes in molecular recognition. However, few examples are reported which show
      that aptamers can be internalized inside living cells for aptamer functional
      studies and for targeted intracellular delivery. This is mainly due to the
      limited number of aptamers available for cell-specific recognition, and the lack
      of research on their extra- and intracellular functions. One of the major
      difficulties in aptamers' in vivo application is that most of aptamers, unlike
      small molecules, cannot be directly taken up by cells without external
      assistance. In this work, we have studied a newly developed and cell-specific DNA
      aptamer, sgc8. This aptamer has been selected through a novel cell selection
      process (cell-SELEX), in which whole intact cells are used as targets while
      another related cell line is used as a negative control. The cell-SELEX enables
      generation of multiple aptamers for molecular recognition of the target cells and
      has significant advantages in discovering cell surface binding molecules for the
      selected aptamers. We have studied the cellular internalization of one of the
      selected aptamers. Our results show that sgc8 is internalized efficiently and
      specifically to the lymphoblastic leukemia cells. The internalized sgc8 aptamers
      are located inside the endosome. Comparison studies are done with the antibody
      for the binding protein of sgc8, PTK7 (Human protein tyrosine kinase-7) on cell
      surface. We also studied the internalization kinetics of both the aptamer and the
      antibody for the same protein on the living cell surface. We have further
      evaluated the effects of sgc8 on cell viability, and no cytotoxicity is observed.
      This study indicates that sgc8 is a promising agent for cell-type specific
      intracellular delivery.

PMID- 18092309
TI  - The chemistry of fluorescent bodipy dyes: versatility unsurpassed.
AB  - The world of organic luminophores has been confined for a long time to fairly
      standard biological labeling applications and to certain analytical tests.
      Recently, however, the field has undergone a major change of direction, driven by
      the dual needs to develop novel organic electronic materials and to fuel the
      rapidly emerging nanotechnologies. Among the many diverse fluorescent molecules,
      the Bodipy family, first developed as luminescent tags and laser dyes, has become
      a cornerstone for these new applications. The near future looks extremely bright
      for "porphyrin's little sister".

PMID- 18092310
TI  - Fully reversible interconversion between locally excited fluorophore, exciplex,
      and radical ion pair demonstrated by a new magnetic field effect.

PMID- 18092311
TI  - Cellular uptake quantification of metalated peptide and peptide nucleic acid
      bioconjugates by atomic absorption spectroscopy.

PMID- 18092312
TI  - One-step synthesis and exploratory chemistry of [5]dendralene.

PMID- 18092313
TI  - Hydrogenation of carbon dioxide is promoted by a task-specific ionic liquid.

PMID- 18092314
TI  - Synthesis of alpha-ketoamides by a molecular-sieves-promoted formal oxidative
      coupling of aliphatic aldehydes with isocyanides.

PMID- 18092315
TI  - Polymeric zinc ferrocenyl sulfonate as a molecular aspirator for the removal of
      toxic metal ions.
AB  - A porous bilayered open coordination polymer [Zn(4,4'-bpy)(2)(FcphSO(3))(2)](n)
      (1; FcphSO(3)Na=m-ferrocenyl benzenesulfonate), has been assembled from
      Zn(NO(3))(2), m-ferrocenyl benzenesulfonate, and the bridging ligand 4,4'
      bipyridine (4,4'-bpy). Ion-exchange induced products [Cd(0.6)Zn(0.4)(4,4'
      bpy)(2)(FcphSO(3))(2)](n) (2), [Zn(0.75)Pb(0.25)(4,4'-bpy)(2)(FcphSO(3))(2)](n)
      (3), and [Cu(0.5)Zn(0.5)(4,4'-bpy)(2)(FcphSO(3))(2)](n) (4) could be obtained
      directly by suspending a big single crystal of 1 into concentrated solutions of
      Cd(NO(3))(2), Pb(NO(3))(2), and Cu(NO(3))(2), respectively. Most importantly, the
      big single crystal of 1 could be partly regenerated after immersion into
      concentrated aqueous solutions of Zn(NO(3))(2). On the other hand, powdered 1
      could also be used as a metal ion adsorbent because of the well-defined pore size
      and pore shape. Ion exchange takes place along with the process of ion sorption.
      The big single crystal of 1 removes harmful metal ions by means of ion exchange,
      whereas powdered 1 removes toxic metal ions mainly through ion sorption. Also,
      compound 1 could be employed as a multi-ion analysis fluorescent probe to detect
      dangerous metal ions, such as Pb(2+), Cd(2+), Ag(+), and Cu(2+). The compounds
      described in this study may have potential applications in the design of new
      molecular devices.

PMID- 18092316
TI  - Birch reduction of hexaphenyl- and pentaphenylbenzene and an X-ray
      crystallography and NMR spectroscopy study of cis- and epi-1,2,3,4,5,6
      hexaphenylcyclohexane and of 2,3,5,6-tetraphenyl-1,1'-bicyclohexylidene:
      Cannizzaro's conundrum revisited.
AB  - The Birch reduction of hexaphenylbenzene yields two isomers of 1,2,3,4,5,6
      hexaphenylcyclohexane. The X-ray crystal structure of the all-cis isomer, 1,
      reveals that the severe steric crowding among the three axial phenyls is
      alleviated by a marked splaying out of those three aryl substituents relative to
      the positioning in a conventional chair structure. A second product, 2, was
      identified crystallographically and by NMR spectroscopy as the 1,3-diaxial
      2,4,5,6-tetraequatorial (epi) isomer of hexaphenylcyclohexane, in which only five
      of the six additional hydrogen atoms are positioned on the same face of the
      C(6)Ph(6) precursor. A variable-temperature NMR study of the all-cis isomer 1
      yielded a chair-to-chair inversion barrier of approximately 19 kcal mol(-1),
      which is somewhat higher than the previously reported values for all-cis
      1,2,3,4,5,6-C(6)H(6)R(6) in which R=Me or CO(2)Me. The possible relevance to
      Cannizzaro's 1854 report of a product with the formula (C(7)H(6))(n) is
      discussed. By contrast, Birch reduction of pentaphenylbenzene led to the
      formation of 2,3,5,6-tetraphenyl-1,1'-bicyclohexylidene.

PMID- 18092317
TI  - Cystic parathyroid adenoma within a multinodular goiter: a rare cause of primary
      hyperparathyroidism.
AB  - Parathyroid cysts are uncommon lesions that do not have a specific sonographic
      appearance. We report a rare case of a functionally active cystic parathyroid
      adenoma as a cause of primary hyperparathyroidism and discuss the difficulties
      associated with the diagnosis. In this case, the association with a multinodular
      goiter made preoperative differentiation from thyroid cysts difficult.
      Demonstration of a high intact parathyroid hormone level in the aspirated cyst
      fluid was critical for the correct diagnosis.

PMID- 18092318
TI  - Comprehensive evaluation of positional candidates in the IL-18 pathway reveals
      suggestive associations with schizophrenia and herpes virus seropositivity.
AB  - Interactions between genetic variation and environmental factors have been
      invoked in schizophrenia genesis, but pathways linking them are uncertain. We
      used a pathway-oriented approach to evaluate six genes mediating IL18 function
      (IL-18, IL18BP, IL18R1, IL18RAP, IL12B, and IL12A). The first five are also
      localized to regions previously linked with schizophrenia. Fifty-four
      representative tag SNPs were selected from comprehensive sequence data and
      genotyped in 478 patients with schizophrenia/schizoaffective disorder (DSM IV
      criteria) and 501 unscreened control individuals. Exposure to three herpes
      viruses previously suggested as risk factors for schizophrenia was estimated
      simultaneously among the cases. Five SNPs in four genes were associated with
      schizophrenia, most prominently rs2272127 at IL18RAP (P = 0.0007, odds ratio for
      C allele 1.49, 95% CI: 1.18-1.87; P = 0.03 following correction for multiple
      comparisons). Exploratory analysis revealed that rs2272127 was also associated
      with herpes simplex virus 1 (HSV1) seropositivity in cases (P = 0.04, OR for G
      allele 1.58, 95% CI: 1.04-2.39). Similar patterns were observed at another
      correlated SNP (rs11465702, P = 0.005 and 0.006, respectively for associations
      with schizophrenia and HSV1 seropositivity). We suggest plausible, testable
      hypotheses linking IL-18 signaling and HSV1 in schizophrenia pathogenesis.

PMID- 18092319
TI  - Catechol-O-methyltransferase Val158Met polymorphism and clinical characteristics
      in first episode non-affective psychosis.
AB  - Catechol-O-methyltransferase (COMT) Val158Met polymorphism has been identified as
      a potential etiologic factor in schizophrenia. It has been proposed that this
      polymorphism could be associated with specific clinical markers. The aim of the
      study was to evaluate the influence of COMT Val158Met polymorphism genotype in
      the phenotypic expression of first episode psychosis at onset. Age of onset, DUP,
      SANS, and SAPS (positive, disorganized, and negative dimensions) were studied in
      169 Caucasian drug-naive patients with a first-episode of non-affective
      psychosis. The COMT Val158Met polymorphism was typed using PCR amplification of
      the relevant region followed by digestion with NlaIII and electrophoresis. A
      multivariate ANCOVA was performed with COMT and gender as independent variables.
      Patients with Val/Val genotype had significantly higher levels of SANS negative
      dimension scores (F: 3.539; P = 0.031) and had a younger age of onset (F: 4.649;
      P = 0.011) than Met carriers. Our findings suggest that the Val allele is
      associated with onset phenotypic features related to a poor prognosis of the
      illness. These data would indicate that COMT genotype may have a role in the
      etiological model for schizophrenia and other psychotic disorders.

PMID- 18092321
TI  - The twenty-second Aspen Cancer Conference: Mechanisms of Toxicity,
      Carcinogenesis, Cancer Prevention, and Cancer Therapy, 2007.

PMID- 18092320
TI  - Common and distinct mechanisms of different redox-active carcinogens involved in
      the transformation of mouse JB6P+ cells.
AB  - We transformed JB6P+ cells with prolonged intermittent low-dose UVB radiation or
      prolonged exposure to low-dose H(2)O(2) or CdCl(2). Stable transformation was
      confirmed by an anchorage-independence assay. The JB6P+ transformants formed more
      colonies (approximately six folds) in soft agar as compared to their JB6P+ parent
      cells and were associated with increased intracellular reactive oxygen species
      (ROS) levels. Activating protein-1 (AP-1) is a family of transcription factors
      that are rapidly activated by elevated intracellular ROS levels, and their
      composition is important in the process of cellular transformation and/or tumor
      progression. To investigate if carcinogenesis induced by distinct carcinogens was
      via similar molecular mechanisms in these transformants, gel mobility shift and
      immunoblot analyses were utilized to determine the distinct AP-1 compositions.
      Compared to parent JB6P+ cells, the gain of JunB and Fra-1 in AP-1 DNA binding
      complexes was markedly increased in all transformed cells, which might contribute
      to a more proliferative phenotype, while loss of Fra-2 occurred in JB6P+/H(2)O(2)
      and JB6P+/Cd cells. Differential AP-1 components in the transformants suggested
      that their transformations might be mediated by distinct transcription signalings
      with distinct AP-1 dimer compositions. However, all three transformants exhibited
      increased activation of pathways involved in cell proliferation (ERK/Fra-1/AP-1
      and JNK/c-jun/AP-1) and anti-apoptosis (Bcl-xl). The development of the JB6P+
      transformants (JB6P+/UVB; JB6P+/H(2)O(2); JB6P+/Cd) provides a unique tool to
      study the mechanisms that contribute to different redox-active carcinogens in a
      single model.

PMID- 18092323
TI  - Fruit and vegetable intake and head and neck cancer risk in a large United States
      prospective cohort study.
AB  - Squamous head and neck cancers include cancers of the oral cavity, pharynx and
      larynx are the sixth leading cause of cancer mortality worldwide, resulting in
      more than 350,000 deaths annually. Intake of fruit and vegetables may protect
      against head and neck cancer incidence, although few prospective studies have
      examined this association. We investigated this relation in 490,802 United States
      participants of the NIH-AARP Diet and Health cohort using Cox proportional hazard
      models adjusted for potential confounders. During 2,193,751 person years of
      follow-up from 1995/1996-2000, 787 participants were diagnosed with head and neck
      cancer. We found an inverse association between total fruit and vegetable intake
      and head and neck cancer risk (per serving/day/1,000 calories, Hazard Ratio, 95%
      Confidence interval: 0.94, 0.89-0.99). In models mutually adjusted for fruit and
      vegetable intake, the association was stronger for vegetables (fifth vs. first
      quintile: 0.65, 0.50-0.85) than for fruits (fifth vs. first quintile: 0.87, 0.68
      1.11). When further subclassified into botanical groups, those in the highest
      tertile of leguminosae (dried beans, string beans and peas, 0.80, 0.67-0.96),
      rosaceae (apples, peach, nectarines, plums, pears and strawberries, 0.60, 0.49
      0.73), solanaceae (peppers and tomatoes, 0.82, 0.69-0.98) and umbelliferae
      (carrots, 0.73, 0.60-0.89) had decreased risk of head and neck cancer, but no
      significant associations were seen for 9 other botanical groups. Results from
      this large prospective observational study are consistent with previous case
      control studies and support the hypothesis that total fruit and vegetable intake
      is associated with reduced risk of head and neck cancer.

PMID- 18092324
TI  - Mutant p53(R270H) gain of function phenotype in a mouse model for oncogene
      induced mammary carcinogenesis.
AB  - In human breast cancer, mutations in the p53 gene are associated with poor
      prognosis. However, analysis of patient data so far did not clarify, whether
      missense point mutations in the p53 gene, in addition to causing loss of wild
      type p53 function, also confer a gain of function phenotype to the encoded mutant
      p53. As heterogeneity of patient material and data might obscure a clear answer,
      we studied the effects of a coexpressed mutant p53(R270H) in transgenic mice in
      which SV40 early proteins initiate the development of mammary adenocarcinoma (WAP
      T mice). In such tumors the endogenous wild-type p53 is functionally compromised
      by complex formation with SV40 T-antigen, thereby constituting a loss of wild
      type p53 function situation that allowed analysis of the postulated gain of
      function effects of mutant p53(R270H). We found that mutant p53(R270H) in bi
      transgenic mice enhanced the transition from intraepithelial neoplasia to
      invasive carcinoma, resulting in a higher frequency of invasive carcinoma per
      gland and per mouse, a more severe tumor phenotype, and more frequent pulmonary
      metastasis. Surprisingly, mutant p53(R270H) in this system does not increase
      genomic instability. Therefore, other postulated gain of function activities of
      mutant p53 must be responsible for the effects described here.

PMID- 18092325
TI  - Experimental anti-angiogenesis causes upregulation of genes associated with poor
      survival in glioblastoma.
AB  - Vascular endothelial growth factor (VEGF) inhibitors are the most promising anti
      angiogenic agents used increasingly in the clinic. However, to be efficient, anti
      VEGF agents need to be associated with classic chemotherapy. Exploring gene
      regulation in tumor cells during anti-angiogenesis might help to comprehend the
      molecular basis of response to treatment. To generate a defined anti-angiogenic
      condition in vivo, we transfected human glioma cells with short-interfering RNAs
      against VEGF-A and implanted them on the chick chorio-allantoic membrane. Gene
      regulation in avascular tumors was studied using human Affymetrixtrade mark
      GeneChips. Potentially important genes were further studied in glioma patients.
      Despite strong VEGF inhibition, we observed recurrent formation of small,
      avascular tumors. CHI3L2, IL1B, PI3/elafin and CHI3L1, which encodes for YKL-40,
      a putative prognosticator for various diseases, including cancer, were strongly
      up-regulated in avascular glioma. In glioblastoma patients, these genes showed
      coregulation and their expression differed significantly from low-grade glioma.
      Importantly, high levels of CHI3L1 (p = 0.036) and PI3/elafin mRNA (p = 0.0004)
      were significantly correlated with poor survival. Cox regression analysis further
      confirmed that PI3 and CHI3L1 levels are survival markers independent from
      patient age and sex. Elafin-positive tumor cells were only found in glioblastoma,
      where they were clustered around necrotic areas. PI3/elafin is strongly induced
      by serum deprivation and hypoxia in U87 glioma cells in vitro. Our results
      indicate that anti-angiogenesis in experimental glioma drives expression of
      critical genes which relate to disease aggressiveness in glioblastoma patients.
      In particular, CHI3L1 and PI3/elafin may be useful as new prognostic markers and
      new therapeutic targets.

PMID- 18092326
TI  - Interaction of estrogen therapy with calcium and vitamin D supplementation on
      colorectal cancer risk: reanalysis of Women's Health Initiative randomized trial.
AB  - Although calcium and vitamin-D intake were consistently shown to be inversely
      associated with colorectal cancer risk in several large prospective studies and
      protective against adenoma and cancer in multiple randomized trials, the Women's
      Health Initiative (WHI) of calcium and low-dose vitamin-D supplementation trial
      found no overall effects on colorectal cancer. However, the previous report did
      not recognize an important biologic interaction with estrogen therapy. We
      investigated the treatment interaction of estrogen with calcium and vitamin-D on
      risk of colorectal cancer via a reanalysis of primary data results from the WHI
      calcium and vitamin-D supplementation trial (1,000 mg elemental calcium, 400 IU
      of vitamin-D3, or placebo), reanalyzing results from women concurrently
      randomized to estrogen interventions and placebo. Results indicate that
      concurrent estrogen therapy was a strong effect modifier of calcium and vitamin-D
      supplementation on colorectal cancer risk. While calcium plus vitamin-D
      supplementation among women concurrently assigned to estrogen therapies suggested
      increased risk (Hazard Ratio = 1.50, 95% CI: 0.96-2.33), among women concurrently
      assigned to placebos arms of the estrogen trials, calcium plus vitamin-D
      indicated suggestive benefits (HR = 0.71, 95% CI: 0.46-1.09) (p-for-estrogen
      interaction = 0.018). Consistent interaction was also found by reported estrogen
      use (p interaction = 0.037). Results indicate contrasting effects of calcium and
      vitamin-D by concurrent estrogen therapy on colorectal cancer risk. Although
      further clinical and mechanistic studies are warranted, the potential clinical
      implications of the apparent interaction of estrogen therapy with calcium and
      vitamin-D supplementation should be recognized. Important biological mechanisms
      related to the key membrane receptor megalin and estrogen-dependent protein
      calbindin are discussed.

PMID- 18092327
TI  - Plasma vitamin B12 concentrations and the risk of colorectal cancer: a nested
      case-referent study.
AB  - In this nested case-referent study, we related plasma concentrations of vitamin
      B12 to the risk of colorectal cancer, taking into consideration prediagnostic
      plasma folate and total homocysteine concentrations. Subjects were 226 cases and
      double matched referents from the population-based Northern Sweden Health and
      Disease Study. Follow-up times from recruitment to diagnosis ranged from 0.1 to
      12.7 years, with a median of 4.2 years. Plasma vitamin B12 concentrations were
      inversely associated with the risk of rectal cancer: univariate odds ratio for
      the highest versus lowest quintile 0.34 (95% confidence interval (95% CI) 0.13
      0.83), p(trend) = 0.004. Risk estimates were attenuated slightly but remained
      statistically significant after adjustment for body mass index, current smoking,
      recreational and occupational physical activity, alcohol intake and prediagnostic
      plasma folate and total homocysteine concentrations: OR 0.30 (95% CI 0.08-0.99),
      p(trend) = 0.025. The corresponding univariate and fully adjusted odds ratios for
      colon cancer were 1.25 (CI 0.66-2.36), p(trend) = 0.185 and 1.42 (CI 0.67-3.05),
      p(trend) = 0.113, respectively. The observed over-risk was attributable to left
      sided colon cancer. Interaction analyses including vitamin B12, folate and
      homocysteine were in line with the results for vitamin B12 alone. In conclusion,
      these results suggest that increasing levels of plasma vitamin B12, alone or
      together with other factors involved in one-carbon metabolism, may reduce the
      risk of rectal cancer, whereas for colon cancer, the association appears to be
      less clear.

PMID- 18092328
TI  - Narrowing of the regions of allelic losses of chromosome 1p36 in meningioma
      tissues by an improved SSCP analysis.
AB  - Mapping loss of heterozygosity (LOH) regions in the genomes of tumor tissues is a
      practical approach for identifying genes whose loss is related to tumorigenesis.
      Conventional LOH analyses using microsatellite or single nucleotide polymorphism
      (SNP) markers require the simultaneous examination of tumor- and matched normal
      DNA. Here, we improved the previously developed SNP-based LOH assay using single
      strand conformation polymorphism (SSCP) analysis, so that LOH in tumor samples
      heavily contaminated with normal DNA can now be precisely estimated, even when
      matched normal DNA is not available. We demonstrate the reliability of the
      improved SSCP-based LOH detection method, called the LOH estimation by
      quantitative SSCP analysis using averaged control (LOQUS-AC), by comparing the
      results with those of the previous "LOH estimated by quantitative SSCP assay"
      (LOQUS) method. Using the LOQUS-AC assay, LOH was detected at a high consistency
      (98.1%) with the previous LOQUS method. We then applied this new method to
      characterize LOH profiles in 130 meningiomas, using 68 SNPs (i.e., a mean inter
      SNP interval of 441 kbp) that are evenly distributed throughout chromosome 1p36.
      Benign, atypical and anaplastic meningiomas exhibited 1p36 LOH at frequencies of
      48.39, 84.62 and 100.00%, respectively, using LOQUS-AC. Subsequently, we detected
      a candidate common LOH region on 1p36.11 that might harbor tumor suppressor genes
      related to malignant progression of meningioma.

PMID- 18092330
TI  - Editorial comment Re: Surgical management of pelvic organ prolapse in women: a
      short version Cochrane review.

PMID- 18092329
TI  - Serum soluble Fas levels and prediction of response to platinum-based
      chemotherapy in epithelial ovarian cancer.
AB  - Epithelial ovarian cancer (EOC) is treated mainly by platinum-based combination
      chemotherapy. Chemotherapy induces apoptosis in which the Fas/Fas ligand pathway
      is important. Serum soluble Fas (sFas) is a biomarker of this pathway and
      functionally inhibits Fas-/FasL-mediated apoptosis. In this study, we have
      investigated the role of sFas in prediction of response to chemotherapy in EOC.
      Thirty-five patients were recruited and their serum sFas levels were estimated by
      ELISA at 4 time points-preoperative (sFas1), postoperative (sFas2),
      midchemotherapy (sFas3) and at the end of chemotherapy (sFas4). The response to
      chemotherapy was documented clinically, radiologically and by CA-125 levels,
      based on which, 2 groups were identified: primary chemosensitive (n = 24) and
      primary chemoresistant (n = 11). Based on the disease status at last follow-up, 2
      groups were identified: No Evidence of Disease (n = 15) and Evidence of Disease
      (n = 20). The primary chemoresistant tumors showed significantly higher median
      sFas2 levels (p = 0.033) with the sFas2/sFas1 ratio > or =1 (p = 0.001). A
      multivariate Cox proportional hazards regression model identified sFas2/sFas1
      ratio as a significant factor for the prediction of response to platinum-based
      chemotherapy (p = 0.011). Receiver operating characteristic (ROC) analysis showed
      that at a ratio of 1.2, sFas2/sFas1 achieved a sensitivity of 82% and specificity
      of 100% for prediction of chemotherapeutic response. sFas2/sFas1 and sFas3/sFas1
      ratio was also higher in patients with evidence of disease (p = 0.018 and p =
      0.028, respectively). Progression-free survival rates in patients with
      sFas2/sFas1 ratio <1 exceeded those with ratio > or =1 (p = 0.004). In
      conclusion, serum sFas is a useful biomarker for predicting response to platinum
      based chemotherapy in EOC.

PMID- 18092331
TI  - Mechanism of bladder dysfunction in idiopathic normal pressure hydrocephalus.
AB  - AIM: To elucidate the mechanism of bladder dysfunction in idiopathic normal
      pressure hydrocephalus (iNPH) by a urodynamic study. METHODS: Forty-two patients
      with possible iNPH, who were diagnosed by clinical symptoms/signs (gait,
      cognitive, and urinary disorders) with typical imaging features (ventricular
      enlargement) and normal cerebrospinal fluid pressure, were enrolled. The subjects
      included 36 men and 6 women; mean age, 72 years (62-83 years). All patients
      underwent a urodynamic test according to the definitions and methods proposed by
      the International Continence Society. RESULTS: Lower urinary tract symptoms were
      seen in 93% of the patients, with storage symptoms (93%) being more common than
      voiding symptoms (71%); and urinary urgency (overactive bladder) (64%)/frequency
      (64%) being more common than urinary incontinence (57%). The mean values for the
      maximum flow rate and post-void residual (PVR) volume were 11.7 ml/sec and 42.1
      ml, respectively. PVR >100 ml was noted in six patients (three men, three women;
      range, 100-228 ml). Although the majority of patients had normal bladder volume
      at the first sensation (mean 134 ml), bladder capacity was small (mean 200 ml)
      and detrusor overactivity was seen in 95% of patients. CONCLUSIONS: While
      incontinence can result secondarily from gait disturbance or dementia, detrusor
      overactivity mostly underlies urinary urgency/frequency and incontinence in iNPH.

PMID- 18092332
TI  - Comparison of sensation-related voiding patterns between continent and
      incontinent women: a study with a 3-day sensation-related bladder diary (SR-BD).
AB  - AIM: To describe and compare voiding patterns on a 3-day sensation-related
      bladder diary (SR-BD) in women with urinary incontinence (UI) and healthy
      volunteers. METHODS: A total of 251 women (224 incontinent patients and 27
      healthy volunteers) who recorded a 3-day SR-BD and underwent standard cystometry
      participated in the study. Parameters from the 3-day SR-BD were compared between
      incontinent patients and healthy volunteers. RESULTS: Compared to continent
      women, all groups of incontinent women noted a significantly higher 24 hr voiding
      frequency, a greater voiding frequency per liter diuresis, a smaller mean voided
      volume for different degrees of bladder sensation with more voids made with
      higher intensity of desire to void. The smallest mean voided volumes for
      different degrees of desire to void and the highest voiding frequency per liter
      diuresis were observed in the urge incontinence group. CONCLUSIONS: There were
      different sensation-related voiding patterns on the 3-day SR-BD from incontinent
      women and healthy volunteers. All incontinence groups had increased bladder
      sensation compared to healthy volunteers. The most severe increase of bladder
      sensation was observed in the patients with urgency incontinence.

PMID- 18092333
TI  - Surgical management of pelvic organ prolapse in women: a short version Cochrane
      review.
AB  - BACKGROUND: Pelvic organ prolapse may occur in up to 50% of parous women. A
      variety of urinary, bowel and sexual symptoms may be associated with prolapse.
      OBJECTIVES: To determine the effects of the many different surgeries in the
      management of pelvic organ prolapse. SEARCH STRATEGY: We searched the Cochrane
      Incontinence Group Specialised Trials Register (searched 3 May 2006) and
      reference lists of relevant articles. We also contacted researchers in the field.
      SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that
      included surgical operations for pelvic organ prolapse. DATA COLLECTION AND
      ANALYSIS: Trials were assessed and data extracted independently by two reviewers.
      Six investigators were contacted for additional information with five responding.
      MAIN RESULTS: Twenty two randomised controlled trials were identified evaluating
      2368 women. Abdominal sacral colpopexy was better than vaginal sacrospinous
      colpopexy in terms of a lower rate of recurrent vault prolapse (RR 0.23, 95% CI
      0.07 to 0.77) and less dyspareunia (RR 0.39, 95% CI 0.18 to 0.86), but the trend
      towards a lower re-operation rate for prolapse following abdominal sacrocolpopexy
      was not statistically significant (RR 0.46, 95% CI 0.19 to 1.11). However, the
      vaginal sacrospinous colpopexy was quicker and cheaper to perform and women had
      an earlier return to activities of daily living. The data were too few to
      evaluate other clinical outcomes and adverse events. The three trials
      contributing to this comparison were clinically heterogeneous. For the anterior
      vaginal wall prolapse, standard anterior repair was associated with more
      recurrent cystoceles than when supplemented by polyglactin mesh inlay (RR 1.39,
      95% CI 1.02 to 1.90) or porcine dermis mesh inlay (RR 2.72, 95% CI 1.20 to 6.14),
      but data on morbidity, other clinical outcomes and for other mesh or graft
      materials were too few for reliable comparisons. For posterior vaginal wall
      prolapse, the vaginal approach was associated with a lower rate of recurrent
      rectocele and/or enterocele than the transanal approach (RR 0.24, 95% CI 0.09 to
      0.64), although there was a higher blood loss and postoperative narcotic use.
      However, data on the effect of surgery on bowel symptoms and the use of
      polyglactin mesh inlay or porcine small intestine graft inlay on the risk of
      recurrent rectocele were insufficient for meta-analysis.Meta-analysis on the
      impact of pelvic organ prolapse surgery on continence issues was limited and
      inconclusive, although about 10% of women developed new urinary symptoms after
      surgery. Although the addition of tension-free vaginal tape to endopelvic fascia
      plication (RR 5.5, 95% CI 1.36 to 22.32) and Burch colposuspension to abdominal
      sacrocolpopexy (RR 2.13, 95% CI 1.39 to 3.24) were followed by a lower risk of
      women developing new postoperative stress incontinence, but other outcomes,
      particularly economic, remain to be evaluated. AUTHORS' CONCLUSIONS: Abdominal
      sacrocolpopexy is associated with a lower rate of recurrent vault prolapse and
      dyspareunia than the vaginal sacrospinous colpopexy. These benefits must be
      balanced against a longer operating time, longer time to return to activities of
      daily living and increased cost of the abdominal approach. The use of mesh or
      graft inlays at the time of anterior vaginal wall repair may reduce the risk of
      recurrent cystocele. Posterior vaginal wall repair may be better than transanal
      repair in the management of rectoceles in terms of recurrence of prolapse. The
      addition of a continence procedure to a prolapse repair operation may reduce the
      incidence of postoperative urinary incontinence but this benefit needs to be
      balanced against possible differences in costs and adverse effects. Adequately
      powered randomised controlled clinical trials are urgently needed.

PMID- 18092334
TI  - Dorsal genital nerve stimulation for the treatment of overactive bladder
      symptoms.
AB  - AIM: To evaluate percutaneous placement of electrodes adjacent to the dorsal
      genital nerve (DGN) and measure the effects of electrical stimulation on symptoms
      of urge incontinence during 1 week of home use. METHODS: Prospective, multicenter
      study. Subjects with urge incontinence underwent percutaneous placement of an
      electrode using local anesthetic. Test stimulation was applied to confirm
      electrode placement and cystometry was conducted with and without application of
      electrical stimulation. A 7-day testing period with the electrode connected to an
      external pulse generator was performed and was followed by a 3-day post-treatment
      test period. Bladder diaries, 24 hr pad tests, and adverse event queries were
      obtained. RESULTS: Twenty-one women were enrolled with an average age of 52.7
      years and average duration of incontinence of 6 years. Percutaneous electrode
      placement required 5-10 min and was well tolerated. There was no relationship
      between the acute effects of stimulation on cystometry and the results during
      home use. Pad weight was reduced by >or= 50% in 13 of 17 subjects (76%) (4 did
      not complete 24 hr pad testing) and 47% of subjects reported >or=50% reduction in
      incontinence episodes. Of the subjects who reported severe urgency at baseline,
      81% experienced a 50% or greater improvement. Seven subjects experienced nine
      adverse events ranging from skin irritation to pain and bruising around the
      electrode exit site. CONCLUSIONS: Electrodes to stimulate the DGN can be placed
      percutaneously and a home testing period showed a reduction in overactive bladder
      symptoms with DGN stimulation.

PMID- 18092335
TI  - Abnormal cellular translocation of alpha-internexin in spinal motor neurons of
      Dystonia musculorum mice.
AB  - Dystonia musculorum (dt) is a mutant mouse with hereditary neuropathy where the
      dysfunction is mainly found in the dorsal root ganglia (DRG) neurons but not in
      the spinal motor neurons. However, the accumulation of intermediate filament (IF)
      proteins in the swelling axons of spinal motor neurons could be found in dt/dt
      mice. In order to understand the pathological role of neuronal IFs in the
      swelling axons of spinal motor neurons from dt/dt mice, we extensively examined
      the distribution of neuronal IF proteins. By immunofluorescence staining, our
      results indicated that alpha-internexin was a major component in the swelling
      axon and showed abnormal translocation in the nuclei of spinal motor neurons in
      dt/dt mice. This abnormal translocation of alpha-internexin in the nuclei of
      spinal motor neurons was also confirmed by Western blotting and immunoelectron
      microscopy. Instead of the 10-nm filamentous structure, a diffuse immunopositive
      pattern of alpha-internexin was observed in the nucleus of spinal motor neurons
      in dt/dt mutants. We further examined the cell death of spinal motor neurons by
      TUNEL assay, and no TUNEL-positive cells could be identified from spinal motor
      neurons in dt/dt mice. From these observations we suggest that abnormal
      accumulation of neuronal IFs in the swelling axons and abnormal translocation of
      alpha-internexin in the nuclei of the spinal motor neurons from dt/dt mice may
      not directly cause cell death of the spinal motor neurons.

PMID- 18092336
TI  - Bladder control, urgency, and urge incontinence: evidence from functional brain
      imaging.
AB  - AIM: To review brain imaging studies of bladder control in subjects with normal
      control and urge incontinence; to define a simple model of supraspinal bladder
      control; and to propose a neural correlate of urgency and possible origins of
      urge incontinence. METHODS: Review of published reports of brain imaging relevant
      to urine storage, and secondary analyses of our own recent observations. RESULTS:
      In a simple model of normal urine storage, bladder and urethral afferents
      received in the periaqueductal gray (PAG) are mapped in the insula, forming the
      basis of sensation; the anterior cingulate gyrus (ACG) provides monitoring and
      control; the prefrontal cortex makes voiding decisions. The net result, as the
      bladder fills, is inhibition of the pontine micturition center (PMC) and of
      voiding, together with gradual increase in insular response, corresponding to
      increasing desire to void. In urge-incontinent subjects, brain responses differ.
      At large bladder volumes and strong sensation, but without detrusor overactivity
      (DO), most cortical responses become exaggerated, especially in ACG. This may be
      both a learned reaction to previous incontinence episodes and the neural
      correlate of urgency. The neural signature of DO itself seems to be prefrontal
      deactivation. Possible causes of urge incontinence include dysfunction of
      prefrontal cortex or limbic system, suggested by weak responses and/or
      deactivation, as well as abnormal afferent signals or re-emergence of infantile
      reflexes. CONCLUSIONS: Bladder control depends on an extensive network of brain
      regions. Dysfunction in various parts may contribute to urge incontinence,
      suggesting that there are different phenotypes requiring different treatments.

PMID- 18092337
TI  - Modulation of expression of LDH isoenzymes in endothelial cells by laminin:
      implications for angiogenesis.
AB  - Endothelial cell (EC) matrix interaction is critical in angiogenesis. Although
      matrix components can regulate the process of angiogenesis by acting as a
      reservoir of various cytokines, it is not clear if extracellular matrix (ECM) can
      modulate the production and activity of angiogenic cytokines. Investigations were
      therefore carried out to study the influence of the basement membrane (BM)
      protein, laminin (Ln) on the activity of vascular endothelial growth factor
      (VEGF), the major angiogenic cytokine, using isolated human umbilical vein ECs
      (HUVECs) in culture. Analysis of the biochemical markers of angiogenesis
      confirmed proangiogenic effect of Ln. The levels of VEGF protein and mRNA were
      not different in cells maintained on Ln, collagen I or polylysine substrata.
      Chorioallantoic membrane assay using VEGF isolated from cell extracts however
      revealed that Ln increased its angiogenic potency. Immunoblotting and HPLC
      analysis showed considerable reduction in poly adenosyl ribosylation of VEGF
      associated with a significant decrease in the levels of NAD+, in cells maintained
      on Ln substrata. Further, a shift in the isoenzymic pattern of LDH towards the B
      rich forms and an upregulation of LDH B gene were observed in cells maintained on
      Ln. Ln modulates expression of LDH gene through alpha(6)beta(4) integrin mediated
      downstream signaling involving p38 mitogen activated protein kinases (MAPK)
      pathway. It thus appears that Ln can affect aerobic metabolism of ECs by
      modulating the expression of LDH isoenzymes resulting in a decrease in the level
      of NAD+ that can cause a reduction in the poly adenosyl ribosylation of VEGF
      altering its angiogenic potency.

PMID- 18092338
TI  - Postmortem fetal organ volumetry using magnetic resonance imaging and comparison
      to organ weights at conventional autopsy.
AB  - OBJECTIVES: Following perinatal death, organ weights at autopsy may provide
      evidence of growth restriction and pulmonary hypoplasia. Whilst postmortem
      magnetic resonance imaging (MRI) may provide comparable information to autopsy
      about structural abnormalities, its ability to provide reproducible data about
      organ size has yet to be determined. We examined the feasibility of using
      postmortem MRI to provide estimates of organ size and weight. METHODS: Twenty
      five fetuses of gestational age from 16 to 40 weeks underwent postmortem MRI
      prior to autopsy. Fetal lung, brain and liver volume estimations were performed
      by two observers using the stereology technique on postmortem MRI slices. Fetal
      lung, brain and liver weights were recorded at autopsy. Organ volume estimates
      and autopsy organ weights were compared using regression analysis, and estimates
      of fetal organ densities made. Interobserver variability was assessed using a
      Bland-Altman plot. Receiver-operating characteristics curve (ROC) analysis
      compared MRI brain : liver volume ratios to autopsy brain : liver weight ratios.
      RESULTS: A linear relationship between organ volume estimates and organ weight
      was observed. Estimated densities for the fetal brain, liver and lung were 1.08
      g/cm(3), 1.15 g/cm(3) and 1.15 g/cm(3), respectively. Interobserver 5th and 95th
      percentile limits of agreement for fetal brain, liver and lung were - 5.4% to +
      7.9%, - 11.8% to + 8.3% and - 14.3% to + 8.7%, respectively. For MRI organ
      volumes to detect a brain weight : liver weight ratio > or = 4, ROC analysis
      demonstrated an area under the curve of 0.61, with an optimal cut-off of 4.1.
      CONCLUSION: Postmortem MRI organ volumetry can be used to estimate weights of
      major fetal organs. This may increase the information obtained from a minimally
      invasive perinatal autopsy, particularly in the context of pulmonary hypoplasia
      and intrauterine growth restriction, where differential organ growth plays a
      major part in assessment of the underlying pathology.

PMID- 18092339
TI  - Bioactive food components and cancer risk reduction.
AB  - Research over the last three decades has provided convincing evidence to support
      the premise that diets rich in fruits and vegetables may be protective against
      the risk of different types of cancers. Initial evidence for protective effect of
      fruits and vegetables against cancer risk came from population-based case-control
      studies, which prompted intense research aimed at (a) identification of bioactive
      component(s) responsible for the anticancer effects of fruits and vegetables, (b)
      elucidation of the mechanisms by which bioactive food components may prevent
      cancer, and (c) determination of their efficacy for prevention of cancer in
      animal models. The bioactive components responsible for cancer chemopreventive
      effects of various edible plants have now been identified. For instance,
      anticancer effect of Allium vegetables including garlic is attributed to
      organosulfur compounds (e.g., diallyl trisulfide). Interestingly, unlike cancer
      chemotherapy drugs, many bioactive food components selectively target cancer
      cells. Molecular basis for selectivity of anticancer bioactive food components
      towards cancer cells remains elusive, but these agents appear promiscuous and
      target multiple signal transduction pathways to inhibit cancer cell growth in
      vitro and in vivo. Despite convincing observational and experimental evidence,
      however, limited effort has been directed towards clinical investigations to
      determine efficacy of bioactive food components for prevention of human cancers.
      This article reviews current knowledge on cancer chemopreventive effects of a few
      highly promising dietary constituents, including garlic-derived organosulfides,
      berry compounds, and cruciferous vegetable-derived isothiocyanates, and serves to
      illustrate complexity of the signal transduction mechanisms in cancer
      chemoprevention by these promising bioactive food components.

PMID- 18092340
TI  - Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist nutlin
      3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B
      cells.
AB  - We have compared the cytotoxic/cytostatic responses of the SKW6.4 lymphoblastoid
      B-cells to the alkylating agent chlorambucil, the purine analog fludarabine, the
      non-genotoxic activator of the p53 pathway, Nutlin-3, used alone or in
      association with the death-inducing ligand recombinant TRAIL. Exposure to
      chlorambucil, fludarabine, and Nutlin-3 induced p53 accumulation and variably
      affected cell cycle progression in SKW6.4 lymphoblastoid cells. In particular,
      chlorambucil induced cell cycle accumulation at the G2/M checkpoint; Nutlin-3
      induced early cell cycle arrest at the G1/S checkpoint, while fludarabine showed
      an intermediate behavior. On the other hand, recombinant TRAIL alone did not
      affect cell cycle progression but induced a rapid increase of apoptosis. Analysis
      of the gene expression profile of the p53-transcriptional targets showed distinct
      features between chlorambucil, Nutlin-3 and fludarabine, which likely account for
      their differential effect on cell cycle in SKW6.4 cells. In particular,
      chlorambucil upregulated the steady-state mRNA expression of SFN/14-3-3sigma, a
      gene involved in G2/M cell cycle arrest. Of note, all agonists upregulated TRAIL
      R2 expression in SKW6.4 cells both at the mRNA and protein levels. Consistently,
      pretreatment with chlorambucil, fludarabine and Nutlin-3 enhanced SKW6.4
      sensitivity to TRAIL-mediated apoptosis.

PMID- 18092341
TI  - Local self-assembly mechanisms underlie the differential transformation of the
      proximal and distal cut axonal ends into functional and aberrant growth cones.
AB  - Following axotomy, both the proximal and distal cut axonal ends transform into
      growth cones (GCs). Whereas the GCs formed by the tip of the proximal segment
      branch to form neurites, the structure formed by the distal cut end fails to
      grow. The mechanisms underlying the formation of an aberrant GC by the distal cut
      end are not understood. Earlier we described the cascade that transforms the tip
      of the proximal cut axon into a GC. This involves microtubule (MT) polar
      reorientation, which culminates in the formation of two MT-based vesicle traps,
      one for Golgi-derived vesicles and the other that retains retrogradely
      transported vesicles. The formation of these traps is the outcome of local
      interactions between dynamically repolymerizing MTs and molecular motors. The
      concentration of Golgi-derived vesicles in the plus-end trap is essential for the
      successful generation of a functional GC. By using online confocal imaging of
      transected cultured Aplysia neurons, we analyzed here the restructuring of the
      distal cut end after axotomy. We found that initially the proximal and distal cut
      ends undergo identical alterations. Nevertheless, in contrast to the proximal
      end, the distal cut axon forms only a minus-end MT-based trap that concentrates
      endocytotic vesicles driven by minus-end oriented motors. Whereas the MTs forming
      the trap polymerize pointing their plus-ends centrifugally to form finger-like
      protrusions, the trapped vesicles cannot translocate out to fuse with the plasma
      membrane. Thus, the structure formed at the distal cut axon is incompetent to
      support growth processes.

PMID- 18092343
TI  - Paracellular entry of interleukin-10 producing Lactococcus lactis in inflamed
      intestinal mucosa in mice.
AB  - BACKGROUND: Genetically modified Lactococcus lactis secreting interleukin-10 (IL
      10) has been demonstrated to provide localized delivery of a therapeutic agent
      through active in situ synthesis in murine colitis. At present, many aspects of
      the exact mechanism by which the beneficial effect of the IL-10-producing L.
      lactis on the mucosa is mediated remain to be clarified. METHODS: Our aim was to
      determine the interaction of L. lactis with the intestinal mucosa. Therefore, we
      administered IL-10-producing L. lactis to healthy mice and in 2 mouse models of
      chronic colitis. Paraffin sections of ileum and colon samples were examined with
      confocal and transmission electron microscopy. Ileum and colon homogenates were
      prepared after flushing and after removal of mucus layer and epithelium. These
      homogenates and homogenates of mesenteric lymph nodes and spleen were plated on
      agar and immunoblotting for L. lactis and IL-10 was performed. RESULTS: Both
      confocal and electron microscopy showed the presence of lactococci in inflamed
      intestinal mucosa of mice with colitis. We recovered viable bacteria that could
      still produce IL-10 from homogenates of inflamed ileum and colon of which mucous
      and epithelial layers were removed. We did not find lactococci in mesenteric
      lymph nodes or in the spleen of mice with colitis. CONCLUSIONS: This study
      demonstrates uptake of IL-10-secreting L. lactis by the paracellular route in
      inflamed mucosal tissue. We suggest that IL-10 production by L. lactis residing
      inside the mucosa in the vicinity of responsive cells can improve the local
      action of interleukin-10 in inflamed tissue and the efficiency of the treatment.

PMID- 18092342
TI  - Griffonia simplicifolia isolectin B4 identifies a specific subpopulation of
      angiogenic blood vessels following contusive spinal cord injury in the adult
      mouse.
AB  - After traumatic spinal cord injury (SCI), disruption and plasticity of the
      microvasculature within injured spinal tissue contribute to the pathological
      cascades associated with the evolution of both primary and secondary injury.
      Conversely, preserved vascular function most likely results in tissue sparing and
      subsequent functional recovery. It has been difficult to identify subclasses of
      damaged or regenerating blood vessels at the cellular level. Here, adult mice
      received a single intravenous injection of the Griffonia simplicifolia isolectin
      B4 (IB4) at 1-28 days following a moderate thoracic (T9) contusion. Vascular
      binding of IB4 was maximally observed 7 days following injury, a time associated
      with multiple pathologic aspects of the intrinsic adaptive angiogenesis, with
      numbers of IB4 vascular profiles decreasing by 21 days postinjury. Quantitative
      assessment of IB4 binding shows that it occurs within the evolving lesion
      epicenter, with affected vessels expressing a temporally specific dysfunctional
      tight junctional phenotype as assessed by occludin, claudin-5, and ZO-1
      immunoreactivities. Taken together, these results demonstrate that intravascular
      lectin delivery following SCI is a useful approach not only for observing the
      functional status of neovascular formation but also for definitively identifying
      specific subpopulations of reactive spinal microvascular elements.

PMID- 18092344
TI  - No association of the CARD8 (TUCAN) c.30T>A (p.C10X) variant with Crohn's
      disease: a study in 3 independent European cohorts.
AB  - BACKGROUND: A recent study reported that the c.30T>A (p.Cys10Ter; rs2043211)
      variant, in the CARD8 (TUCAN) gene, is associated with Crohn's disease (CD). The
      aim of this study was to analyze the frequency of p.C10X in 3 independent
      European (IBD) cohorts from Germany, Hungary, and the Netherlands. METHODS: We
      included a European IBD cohort of 921 patients and compared the p.C10X genotype
      frequency to 832 healthy controls. The 3 study populations analyzed were: (1)
      Germany [CD, n = 317; ulcerative colitis (UC), n = 180], (2) Hungary (CD, n =
      149; UC, n = 119), and (3) the Netherlands (CD, n = 156). Subtyping analysis was
      performed in respect to NOD2 variants (p.Arg702Trp, p.Gly908Arg, c.3020insC) and
      to clinical characteristics. Ethnically matched controls were included (German, n
      = 413; Hungarian, n = 202; Dutch, n = 217). RESULTS: We observed no significant
      difference in p.C10X genotype frequency in either patients with CD or patients
      with UC compared with controls in all 3 cohorts. Conversely to the initial
      association study, we found a trend toward lower frequencies of the suggestive
      risk wild type in CD from the Netherlands compared with controls (P = 0.14). We
      found neither evidence for genetic interactions between p.C10X and NOD2 nor the
      C10X variant to be associated with a CD or UC phenotype. CONCLUSIONS: Analyzing 3
      independent European IBD cohorts, we found no evidence that the C10X variant in
      CARD8 confers susceptibility for CD.

PMID- 18092345
TI  - Mucosal NOD2 expression and NF-kappaB activation in pediatric Crohn's disease.
AB  - BACKGROUND: Recent advances in the pathogenesis of Crohn's disease (CD) have
      suggested that an aberrant innate immune response initiates the cascade of events
      leading to T-cell activation and to disease development. NOD2 protein, which is
      mainly expressed by innate immunity cells, appears to play a key role against
      bacteria by triggering a host defense response through the activation of the
      transcriptor factor NF-kappaB and a consequent proinflammatory cytokine
      production. The present study was aimed at investigating the expression and
      activity of NOD2, NF-kappaB, and of 2 proinflammatory cytokines, TNFalpha and IL
      1beta, in mucosal biopsies of CD affected children compared to healthy controls.
      METHODS: In all, 22 children with active CD and 10 matched controls were entered
      in the study. mRNA and protein expressions were detected using reverse
      transcriptase polymerase chain reaction (RT-PCR) and Western blot; NF-kappaB
      binding activity was assessed by electromobility gel shift assay (EMSA). RESULTS:
      NOD2 and IL-1beta mRNAs were upregulated in CD children. Protein levels of NOD2,
      TNFalpha, and nuclear NF-kappaB, as well as the binding activity of NF-kappaB to
      a consensus DNA sequence, were significantly increased in inflamed mucosa of
      patients as compared to controls. Moreover, NF-kappaB activity was strongly
      upregulated in patients also when bound to the NOD2 promoter site. No difference
      was seen between patients and controls when NF-kappaB binding activity was
      determined in the uninflamed tissue. CONCLUSIONS: This study suggests that
      altered mechanisms regulating NOD2 induction, NF-kappaB activation and cytokine
      production may contribute to dysregulate the innate immune response underlying
      pediatric CD.

PMID- 18092346
TI  - Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine
      models of inflammatory bowel disease.
AB  - BACKGROUND: Despite some progress in recent years, the options for treating
      inflammatory bowel disease (IBD) are still dissatisfying, and surgery rates are
      still high. The anti-inflammatory effects of melanocortin peptides such as alpha
      melanocyte-stimulating hormone (alpha-MSH) have been described recently in, for
      example, dextran sodium sulfate (DSS) colitis in mice. The aim of this study was
      to investigate the therapeutic potential of the melanocortin-derived tripeptide
      alpha-MSH(11-13) (KPV) and its mode of action in 2 models of intestinal
      inflammation. METHODS: The anti-inflammatory activity of KPV was analyzed in 2
      well-described models of IBD: DSS colitis, and CD45RB(hi) transfer colitis.
      Furthermore, animals expressing a nonfunctional melanocortin-1 receptor (MC1Re/e)
      received DSS for induction of colitis and were treated with KPV. The course of
      inflammation was monitored by weight loss and histological changes in the colon
      as well as by myeloperoxidase (MPO) activity. RESULTS: In the DSS-colitis model,
      treatment with KPV led to earlier recovery and significantly stronger regain of
      body weight. Histologically, inflammatory infiltrates were significantly reduced
      in KPV-treated mice, which was confirmed by the significant reduction of MPO
      activity in colonic tissue after KPV treatment. Supporting these findings, KPV
      treatment of transfer colitis led to recovery, regain of body weight, and reduced
      inflammatory changes histologically. In MC1Re/e mice, KPV treatment rescued all
      animals in the treatment group from death during DSS colitis. CONCLUSIONS: The
      melanocortin-derived tripeptide KPV showed significant anti-inflammatory effects
      in 2 murine models of colitis. These effects seem to be at least partially
      independent of MC1R signaling. In conclusion, our data suggest KPV as an
      interesting therapeutic option for the treatment of IBD.

PMID- 18092347
TI  - Dietary patterns and risk for Crohn's disease in children.
AB  - BACKGROUND: Some dietary foods are considered protective (vegetables and fruits),
      whereas others (fatty foods) are thought to enhance the risk for Crohn's disease
      (CD). The evidence, however, is inconsistent. METHODS: We postulated that
      specific dietary patterns may influence the risk for CD. A case-control study was
      carried out. Newly diagnosed CD cases with population and/or hospital-based
      controls < or =20 years were selected from 3 tertiary hospitals across Canada.
      Pre-disease diet was assessed using a validated food frequency questionnaire
      (FFQ) administered within 1 month of diagnosis. Factor analyses and unconditional
      logistic regression (adjusted) was used to determine gender-specific dietary
      patterns and assess associated risks for CD. Odds ratios (ORs) and corresponding
      95% confidence intervals (95% CIs) were estimated. RESULTS: A total of 149 cases
      and 251 controls were included. The mean age (range) of the cases was 13.3 (2.6
      20 years). There were more boys (61.1%). Four dietary patterns each were observed
      among both boys and girls. Pattern 1 in girls, characterized by meats, fatty
      foods, and desserts, was positively associated with CD (OR 4.7, 95% CI 1.6-14.2).
      Pattern 2, common to both boys and girls, was characterized by vegetables,
      fruits, olive oil, fish, grains, and nuts and was inversely associated with CD in
      both genders (girls: OR 0.3, 95% CI 0.1-0.9; boys: OR 0.2, 95% CI 0.1-0.5).
      CONCLUSIONS: Our results suggest that specific dietary patterns could be
      associated with higher or lower risks for CD in children. Larger prospective
      studies are required to confirm these findings.

PMID- 18092348
TI  - Recombinant human epidermal growth factor enhances wound healing of pyoderma
      gangrenosum in a patient with ulcerative colitis.

PMID- 18092349
TI  - Childhood asthma epidemiology: insights from comparative studies of rural and
      urban populations.
AB  - Asthma is one of the most common chronic respiratory disorders. Many epidemiology
      studies have suggested an increasing trend of asthma in many different regions of
      the world but the exact reasons explaining such trend remain unclear.
      Nevertheless, changing environmental factors are most likely important in
      explaining the trend of asthma. Studies in the past decade have clearly shown a
      mark difference in the prevalence between urban and rural regions. The consistent
      findings of a markedly lower prevalence of asthma in children and adults who have
      been brought up in a farming environment clearly indicate the importance of
      environmental influence of asthma development. Although the exact protective
      environmental factors in the rural region remain to be defined, there have been
      many studies suggesting that early exposure to microbes or microbial products may
      play a role in modulating the immune system so as to reduce the future risk of
      asthma and allergies. Advances in the understanding of the genetic predisposition
      and how these genetic factors may interact with specific environment factors are
      of paramount importance for the future development of primary preventive
      strategies for asthma.

PMID- 18092350
TI  - DNA demethylation and histone deacetylation inhibition co-operate to re-express
      estrogen receptor beta and induce apoptosis in prostate cancer cell-lines.
AB  - INTRODUCTION: Epigenetic silencing mechanisms are increasingly thought to play a
      major role in the development of human cancers, including prostate cancer.
      Promoter CpG island hypermethylation and histone hypoacetylation, catalyzed by
      DNA methyltransferase (DNMT) and histone deacetylase (HDAC), respectively, are
      associated with transcriptional repression in a number of cancers. Evidence is
      accumulating the two mechanisms are dynamically linked, yet few studies have
      examined a potential interaction in prostate cancer. METHODS: LNCaP, DU-145, and
      PC-3 prostate cancer cells were co-treated with a DNMT inhibitor, 5'-aza-2'
      deoxycytidine (5-AZAC), and an HDAC inhibitor, trichostatin A (TSA). Following
      treatment cells were processed for cell proliferation/apoptosis assays, or
      harvested for real-time RT-PCR. Assessed target genes were estrogen receptor beta
      (ERbeta), estrogen receptor alpha (ERalpha), androgen receptor (AR), progesterone
      receptor (PGR), and prostate specific antigen (PSA). RESULTS: In all cell-lines,
      co-treatment was associated with reduced cell proliferation compared with control
      groups (P<0.05). A reciprocal rise in caspase activation was identified,
      indicating apoptosis was the major mechanism of cell death. Most marked effects
      were seen in the androgen-dependent, AR-positive LNCaP cell-line. In all cell
      lines, an additive re-expression of ERbeta was identified in the co-treatment
      group, a finding not seen for either AR or PSA. CONCLUSION: At concentrations
      associated with gene re-expression, the DNA demethylating agent 5-AZAC and the
      HDAC inhibitor TSA co-operate to induce apoptosis in prostate cancer cell-lines.
      Increased apoptosis in the co-treatment group was associated with marked re
      expression of ERbeta, raising the possibility of further targeting of prostate
      cancer cells with ERbeta-selective agents.

PMID- 18092351
TI  - Counting alleles in single lesions of prostate tumors from ethnically diverse
      patients.
AB  - BACKGROUND: The presence of racial disparities in incidence and mortality rates
      are well-documented for prostate cancer. Nevertheless, it is unclear whether such
      disparities are due to genetic alterations that are involved in prostate cancer
      initiation. Here, we evaluated chromosome 8p allelic loss in a racially diverse
      cohort. METHODS: Laser-capture microdissection was used to isolate tumors cells
      from individual lesions in 153 prostate cancer patients, and 8p allelic status
      was determined by "counting alleles." Statistical analyses examined the
      association between pathologic predictors and biochemical recurrence. RESULTS AND
      CONCLUSIONS: Thirty percent of prostate lesions were missing an 8p allele at
      tumor initiation, while 51% of lesions lost an 8p allele during tumor
      progression. Biochemical recurrence after radical prostatectomy could be reliably
      predicted by surgical margin status only in lesions with extensive 8p allelic
      loss. There was, however, no racial disparity in 8p allelic loss at tumor
      initiation or during tumor progression, suggesting that the molecular event
      involved was similar between Caucasians and Africa Americans (CA and AA).
      Nonetheless, racial differences were present in values of prognostic factors for
      recurrence. Gleason score was the most important predictor of recurrence (HR=3.1,
      95% CI=1.1, 9.2) in AA, while among CA, pathologic stage (HR=3.3, 95% CI=1.5,
      7.6) and surgical margin (HR=4.7, 95% CI=1.8, 12.6) were the most important.
      Therefore, racial disparity in prostate cancer may be due to other factors that
      are involved in prostate cancer development.

PMID- 18092352
TI  - The toll-like receptor pathway: a novel mechanism of infection-induced
      carcinogenesis of prostate epithelial cells.
AB  - BACKGROUND: Inflammation and infection have been linked to the pathogenesis of
      many cancers including prostate cancer. Components of bacteria and viruses have
      been identified within pathological specimens of men with prostate cancer.
      METHODS: We characterized the in vitro response of benign prostate epithelial
      cells to components of infectious agents as they relate to toll-like receptors.
      RESULTS: Primary and immortalized prostate epithelial cells (RWPE) exhibited
      increased proliferation in response to exposure to lipopolysaccharide (LPS) and
      CpG DNA. These molecules are well-characterized surrogates for gram negative
      bacteria (e.g., E. coli) and DNA viruses (e.g., HPV and HSV), which are common in
      the genitourinary system. Our experiments show that RWPE cells express both TLR 4
      (LPS-specific) and TLR 9 (CpG-specific). Targeted knock down of individual TLR
      expression using siRNA abrogated the proliferative response of RWPE cells to LPS
      and CpG, respectively. In addition, compared to non-stimulated cells, LPS and CpG
      up-regulate active NF-kB expression. Increased NF-kB activation was confirmed
      using RWPE cells that were stably transfected with a NF-kB reporter construct.
      Interestingly, NF-kB activation was both concentration- and time-dependent when
      stimulated with LPS. RWPE cells were less susceptible to TNF-alpha induced
      apoptosis as measured by TUNEL staining when stimulated with CpG or LPS. High
      concentrations of LPS also prevented cell death as measured by LDH release.
      CONCLUSIONS: Our study has identified a unique mechanism that describes how
      components of pathogens common in the urinary system may contribute to the
      malignant transformation of benign prostate epithelia.

PMID- 18092353
TI  - Interactions between stainless steel, shear stress, and monocytes.
AB  - Angioplasty with stent placement is commonly used to treat coronary
      atherosclerosis. However, 20-40% of stainless steel stents restenose within 6
      months via a prolonged inflammatory response mediated by monocytic infiltration
      and cytokine secretion. In the current study, we tested a hypothesis that blood
      flow and monocytes interact to alter stent corrosion. We assessed the effects of
      THP1 monocytes on the corrosion rate of 316L stainless steel (316LSS) under shear
      stress (0.5-50 dyn/cm(2)). In addition, THP1 cytokine secretion was determined
      using cytokine arrays and ELISA analyses. Data were compared using ANOVA and
      Tukey post hoc analysis (alpha = 0.05). Monocytes significantly lowered 316LSS
      corrosion rates without limiting current density. However, shear stress alone did
      not alter the corrosion rate of 316LSS. THP1 cells adhered to the 316LSS surface
      at all flow rates. Exposure to the 316LSS/corrosion test under high fluid flow
      rates increased (>twofold) the secretion of 7 of the 42 cytokines tested
      (angeogenin, GRO, I309, interleukin 8, interleukin 6, interleukin 1beta, and
      macrophage chemoattractant protein-1). Each of these cytokines play a role in
      wound healing, macrophage differentiation, and cell proliferation, all hallmarks
      of in-stent restenosis. Furthermore, only IL8 levels were significantly higher
      than any of the system controls during the 316LSS/corrosion test conditions. The
      IL8 levels from the 316LSS/corrosion tests were not significantly different from
      the +LPS control. Together, these data suggest that monocytic cells maybe
      activated by exposure to 316LSS stents and could contribute to in-stent
      restenosis and altered corrosion of the stent.

PMID- 18092354
TI  - Morphology controllable nanostructured chitosan matrix and its cytocompatibility.
AB  - It is becoming clear that surface nanotopography of underlying substrates can
      influence cell behavior such as adhesion, proliferation, and orientation of
      mammalian cells. Nanofabrication methods such as electron beam lithography are,
      however, expensive and time consuming. In this study, a simple and cost-effective
      approach, heterogeneous seeded growth, was developed to create nanostructured
      chitosan matrix (CSM) from amorphous chitosan nanoparticles (CNPs). The
      physiochemical properties of CSM were characterized followed by an evaluation of
      CSM cytocompatibility. Shape-controllable morphology of CSM from nanoparticles to
      three-dimensional urchin-like architectures was achieved by using varying amounts
      of seeds. CSM was found to be cytocompatible with human foreskin fibroblasts
      suggesting that the nanofibrous surface morphology and crystalline structure of
      CSM could favor cell spread and growth.

PMID- 18092355
TI  - A randomized trial of delayed extubation for the reduction of reintubation in
      extremely preterm infants.
AB  - OBJECTIVE: To compare immediate extubation versus delayed extubation after 36 hr
      in extremely low-birth weight infants receiving gentle mechanical ventilation and
      perinatal lung protective interventions. Our hypothesis was that a delayed
      extubation in this setting would decrease the rate of reintubation. STUDY
      DESIGN/METHODOLOGY: A prospective, unmasked, randomized, controlled trial to
      compare immediate extubation and delayed extubation after 36 hr. Optimized
      ventilation in both groups included continuous tracheal gas insufflation (CTGI),
      prophylactic surfactant administration, low oxygen saturation target and moderate
      permissive hypercapnia. Successful extubation for at least 7 days was the primary
      criterion and ventilatory support requirements until 36 weeks gestational age the
      main secondary criteria. PATIENT SELECTION: Eighty-six infants under 28 weeks
      gestational age in a single neonatal intensive tertiary care unit. RESULTS:
      Delayed extubation (1.9 +/- 0.8 days vs. 0.5 +/- 0.7 days) did not improve the
      rate of successful extubation but had no long-term adverse effects. CTGI and the
      lung protective strategy we describe resulted in a very gentle ventilation. The
      rate of survival without bronchopulmonary dysplasia (BPD, defined as any
      respiratory support at 36 weeks gestational age) was similar in the two groups
      and remarkably high for the global population (78%) and for the subgroup of
      infants <1,000 g at birth (75%). CONCLUSIONS: Adding 36 hr of optimized
      mechanical ventilation before first extubation does not improve the rate of
      successful extubation but has no adverse effects.

PMID- 18092356
TI  - Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome
      drug candidate, decreased vulnerability of PC12 cells to human immunodeficiency
      virus tat protein through attenuating calcium overload.
AB  - Human immunodeficiency virus (HIV)-1 infection of the central nervous system
      occurs in the vast majority of HIV-infected patients. HIV-associated dementia
      (HAD) represents the most severe form of HIV-related neuropsychiatric impairment.
      The pathogenesis of HAD is mediated by disruption of neuronal cell signal
      pathways, which ultimately triggers neuronal apoptosis. Evidence indicates that a
      viral gene product, the transactivator of transcription protein (Tat), takes a
      responsive role to these events. We herein report that sulfated
      polymannuroguluronate (SPMG), a novel anti-acquired immunodeficiency syndrome
      drug candidate now in phase II clinical trial, significantly decreased
      vulnerability of PC12 cells to HIV Tat protein by protecting cells from
      apoptosis. Furthermore, SPMG potently arrested Tat-triggered PKCdelta and
      PKCtheta activation and blocked the downstream apoptosis signaling pathways
      mediated by both ERK1/2 and caspase-3. These molecular mechanisms were attributed
      to the fact that SPMG reduced Tat-evoked calcium overload. These data demonstrate
      that SPMG might serve as a valuable therapeutic intervention for Tat-induced
      neuronal cell death and the subsequent pathologic events of HAD.

PMID- 18092357
TI  - Neuroserpin regulates N-cadherin-mediated cell adhesion independently of its
      activity as an inhibitor of tissue plasminogen activator.
AB  - Neuroserpin is an inhibitor of tissue plasminogen activator (tPA) that is
      expressed in developing and adult nervous systems. Spatial and temporal analysis
      of neuroserpin expression suggests that it is involved in regulating the
      proteolytic balance associated with axonogenesis and synaptogenesis during
      development and synaptic plasticity in the adult. Here we demonstrate that
      altered expression of neuroserpin modulates the degree of cell-cell adhesion in
      pheochromocytoma PC12 cells independently of its role as an inhibitor of tPA.
      Levels of the homophilic cell-cell adhesion molecule N-cadherin are increased in
      neuroserpin-overexpressing cell lines. N-cadherin immunoreactivity was detected
      in a Triton X-100-insoluble fraction and localized to regions of cell contact,
      consistent with a role in enhancing cell surface adhesion. PC12 cell lines
      expressing neuroserpin mutants that lack tPA inhibitory activity also showed
      increased cell-cell adhesion and N-cadherin expression. Our results identify
      neuroserpin as a novel regulator of cell-cell adhesion and the synaptic adhesion
      molecule N-cadherin as a key effecter in this response. In nerve cells,
      neuroserpin may regulate the levels of N-cadherin available for construction,
      maintenance, and control of synapses and synaptic dynamics.

PMID- 18092358
TI  - Protective effects of lipopolysaccharide preconditioning against nitric oxide
      neurotoxicity.
AB  - We have characterized lipopolysaccharide (LPS) preconditioning-induced
      neuroprotective mechanisms against nitric oxide (NO) toxicity. Pretreatment of
      rat cortical cultures with LPS attenuated neurotoxicity of NO donors, including
      sodium nitroprusside (SNP) and diethylamine NONOate (NONOate). A transiently
      increased expression of endothelial nitric oxide synthase (eNOS) accompanied by
      an increase in NO production was observed during LPS preconditioning. Application
      of NOS inhibitors including L-N(5)-(1-iminoethyl)-ornithine (L-NIO) and L
      nitroarginine methylester (L-NAME) abolished LPS-dependent protection against SNP
      toxicity. The LPS effect was also blocked by KT5823, an inhibitor of cGMP
      dependent protein kinase (PKG). Consistently, application of 8-bromo-cyclic GMP
      (8-Br-cGMP), a slowly degradable cGMP analogue capable of PKG activation, was
      neuroprotective. LPS preconditioning resulted in a heightened neuronal expression
      of Bcl-2 protein that was abolished by L-NAME and KT5823, the respective
      inhibitors of NOS and PKG. Together, our results reveal the signaling cascade of
      "LPS --> eNOS --> NO --> cGMP/PKG --> Bcl-2" that might have contributed to the
      LPS protective effects in cortical neurons.

PMID- 18092359
TI  - Yin yang 1 directly regulates the transcription of RE-1 silencing transcription
      factor.
AB  - The RE-1 silencing transcription factor (REST) is a master transcription factor
      that plays a critical role in embryo development, especially during the process
      of neurogenesis and neural plasticity. However, the mechanism of REST gene
      transcription regulation is still an open question. Here, by combining
      bioinformatics analysis and experimental studies, we report that the
      transcription factor Yin Yang 1 (YY1) bound to a conserved YY1 binding site in
      the promoter of the mouse REST gene and positively regulated activity of this
      promoter in SH-SY5Y cells. Furthermore, analysis of microarray data revealed a
      significant correlation between the expression of YY1 and REST genes. Overall,
      this study suggests that YY1 directly regulates expression of the REST gene.

PMID- 18092361
TI  - Water-deprivation-induced expression of neuronal nitric oxide synthase in the
      hypothalamic paraventricular nucleus of rat.
AB  - This study was conducted to define the molecular mechanism by which dehydration
      induces expression of neuronal nitric oxide synthase (nNOS) in the hypothalamic
      paraventricular nucleus (PVN). Rats were deprived from water for 48 hr and then
      sacrificed immediately or 1 hr after ad libitum access to water. Another group of
      rats had free access to food and water and was included as euhydrate control
      group. The PVN sections fixed with 4% paraformaldehyde were processed for nNOS
      immunohistochemistry and NADPH-diaphorase (NADPH-d)/pCREB or NADPH-d/c-Fos double
      staining. nNOS-ir neurons significantly increased with water deprivation and
      decreased with rehydration, both in the posterior magnocellular (pM)- and the
      medial parvocellular (mP)-PVN. Most NADPH-d histostained neurons in the PVN
      appeared to exhibit pCREB-ir as well. Water deprivation markedly increased, and
      rehydration decreased, NADPH-d/pCREB neurons both in the pM- and in the mP-PVN.
      Gel shift assay demonstrated that dehydration may promote CREB binding to nNOS
      promoter in the PVN neurons. Significant amounts of NADPH-d-stained neurons in
      the PVN of water-deprived rats (67-68% in both the mP and the pM) exhibited c-Fos
      ir. NADPH-d/c-Fos neurons in the pM-PVN were increased by water deprivation but
      not changed by rehydration. NADPH-d/c-Fos double-stained neurons in the mP-PVN
      did not significantly change depending on different water conditions. These
      results suggest that pCREB may play a role in dehydration-induced nNOS gene
      expression in the PVN neurons, and c-Fos might not be implicated in the
      regulatory pathway.

PMID- 18092362
TI  - Applied anatomy of the superficial branch of the radial nerve.
AB  - The superficial branch of the radial nerve (SBRN) is highly vulnerable to trauma
      and iatrogenic injury. This study aimed to map the course of the SBRN in the
      context of surgical approaches and identify a safe area of incision for de
      Quervain's tenosynovitis. Twenty-five forearms were dissected. The SBRN emerged
      from under brachioradialis by a mean of 8.31 cm proximal to the radial styloid
      (RS), and remained radial to the dorsal tubercle of the radius by a mean of 1.49
      cm. The nerve divided into a median of four branches. The first branch arose a
      mean of 4.92 cm proximal to the RS, traveling 0.49 cm radial to the first
      compartment of the extensor retinaculum, while the main nerve remained ulnar to
      it by 0.64 cm. All specimens had branches underlying the traditional transverse
      incision for de Quervain's release. A 2.5-cm longitudinal incision proximal from
      the RS avoided the SBRN in 17/25 cases (68%). In 20/25 specimens (80%), the SBRN
      underlay the cephalic vein. In 18/25 (72%), the radial artery was closely
      associated with a sensory nerve branch near the level of the RS (SBRN 12/25,
      lateral cutaneous nerve of the forearm (LCNF) 6/25.) A longitudinal incision in
      de Quervain's surgery may be preferable. Cannulation of the cephalic vein in the
      distal third of the forearm is best avoided. The close association between the
      radial artery and first branch of the SBRN or the LCNF may explain the pain often
      experienced during arterial puncture. Particular care should be taken during
      radial artery harvest to avoid nerve injury.

PMID- 18092360
TI  - Modeling the neurovascular niche: murine strain differences mimic the range of
      responses to chronic hypoxia in the premature newborn.
AB  - Preterm birth results in significant cognitive and motor disabilities, but recent
      evidence suggests that there is variable recovery over time. One possibility that
      may explain this variable recovery entails variable neurogenic responses in the
      subventricular zone (SVZ) following the period of chronic hypoxia experienced by
      these neonates. In this report, we have characterized the responses to chronic
      hypoxia of two mouse strains that represent a wide range of susceptibility to
      chronic hypoxia. We determined that C57BL/6 pups and neural progenitor cells
      (NPCs) derived from them exhibit a blunted response to hypoxic insult compared
      with CD-1 pups and NPCs. Specifically, C57BL/6 pups and NPCs exhibited blunted in
      vivo and in vitro proliferative and increased apoptotic responses to hypoxic
      insult. Additionally, C57BL/6 NPCs exhibited lower baseline levels and hypoxia
      induced levels of selected transcription factors, growth factors, and receptors
      (including HIF-1alpha, PHD2, BDNF, VEGF, SDF-1, TrkB, Nrp-1, CXCR4, and NO) that
      determine, in part, the responsiveness to chronic hypoxic insult compared with CD
      1 pups and NPCs, providing insight into this important and timely problem in
      perinatology.

PMID- 18092363
TI  - Fibularis tertius: some true facts.

PMID- 18092365
TI  - Predicting first molar width using virtual models of dental arches.
AB  - In dentistry, large regions of dentition often are restored with minimal
      information about the original anatomy. The ability to predict missing anatomy
      from existing anatomy would aid such restorations. This study investigated the
      relationship between first molar mesial-distal width and arch shape using newly
      defined reference points and three-dimensional (3D) digital methods. Full-mouth
      dental stone casts from 167 dental students were scanned and rendered as 3D
      virtual models. Maxillary and mandibular arch lengths and widths and first molar
      mesial-distal widths were measured on the virtual models using new definitions
      incorporating virtual planes. A linear mixed model of the first molar width
      regressed on the other measurements was done. Intraobserver reproducibility was
      evaluated by means of intraclass correlation (ICC) and standard deviation of
      measurement error (SDME). All measured distances were averaged as a combined
      group and as gender groups. The correlation coefficients between the maxillary
      and mandibular first molar widths were over 0.70 (P < 0.01). Intraobserver error
      was small. ICCs were over 0.92 and SDMEs were from 0.11 to 0.21 mm. Arch
      dimensions and first molar widths were defined and measured. Regression equations
      were calculated for predicting first molar width. The prediction of first molar
      width using arch dimension is essential for virtual designing of missing first
      molars. This approach also provides reliable reference point definitions for the
      virtual dental model which was impossible with traditional measurement methods.
      Therefore, this study would be helpful for understanding the 3D anatomy of dental
      arch and fabrication of automatic prosthodontic restorations.

PMID- 18092366
TI  - The inguinal ligament and its lateral attachments: correcting an anatomical
      error.
AB  - The inguinal portions of the internal oblique and transversus abdominis muscles
      are generally described as arising from the inguinal ligament. Previous authors
      have shown that this description is incorrect. A new dissection study in 15
      lightly embalmed cadavers confirms that in reality the inguinal portions of these
      muscles arise from a thickened strip of ilipsoas fascia that forms the
      superolateral part of the ilio-pectineal arch. Details are given of a new
      dissection technique that fully exposes the deep aspect of the inguinal ligament,
      without disrupting its continuity. The historical background of the persistent
      textbook error is explored. It originated at a time when there was widespread
      descriptive and semantic confusion regarding the structure now known as the
      inguinal ligament.

PMID- 18092367
TI  - Assessment of female and male fertility in Sprague-Dawley rats administered
      vorinostat, a histone deacetylase inhibitor.
AB  - BACKGROUND: Histone deacetylase (HDAC) inhibitors have been shown to mediate the
      regulation of gene expression, induce cell growth, cell differentiation, and
      apoptosis of tumor cells. These compounds are now marketed or are in clinical
      development. One such HDAC inhibitor, vorinostat (suberoylanilide hydroxamic acid
      [SAHA], Zolinza), was assessed for its potential effects on fertility in Sprague
      Dawley rats. METHODS: Female rats were administered oral dose levels of 0
      (vehicle only), 15, 50, or 150 mg/kg/day of vorinostat for 14 days before
      cohabitation, during cohabitation, and through Gestation Day (GD) 7. In a
      separate study, male rats were administered oral dose levels of 0 (vehicle only),
      20, 50, or 150 mg/kg/day for 10 weeks before cohabitation, during cohabitation,
      and until the day before scheduled sacrifice (approximately 14 weeks total). In
      both studies, % peri-implantation loss and % postimplantation loss were evaluated
      on GD 15-17. Testicular weight and histomorphology, cauda epididymal sperm count,
      and sperm motility were evaluated in the male rat study at termination. RESULTS:
      There were treatment-related decreases in body weight gain at 150 mg/kg/day in
      both studies. There were no effects on mating or fertility indices in either
      study. In the female study there were increased numbers of corpora lutea in all
      drug-treated groups (only 1 or 2 affected dams in low and mid-dose groups), and a
      marked increase in percent postimplantation loss only in the high-dose group. No
      treatment-related effects were observed on litter or sperm parameters of the male
      study. CONCLUSIONS: Vorinostat had no effects on mating or fertility in rats up
      to 150 mg/kg/day. There were no indications of reproductive toxicity in drug
      treated male rats. Increases in corpora lutea or resorptions were observed in
      treated female rats.

PMID- 18092369
TI  - Abstracts of the American Society of Hematology 49th Annual Meeting, December 8
      11, 2007, Atlanta, Georgia, USA.

PMID- 18092370
TI  - Abstracts of the American Society of Hematology 49th Annual Meeting, December 8
      11, 2007, Atlanta, Georgia, USA.

PMID- 18092371
TI  - Abstracts of the 4th International Conference on Children's Bone Health, June 21
      24, 2007, Montreal, Canada.

PMID- 18092373
TI  - Abstracts of the Society of Critical Care Medicine's 37th Critical Care Congress,
      February 2-6, 2008, Honolulu, Hawaii, USA.

PMID- 18092372
TI  - Abstracts of the 17th Scientific Meeting of the International Bone and Mineral
      Society, June 2007, Montreal, Canada.

PMID- 18092374
TI  - [Epicrises from private hospitals].

PMID- 18092375
TI  - [Back and radiology].

PMID- 18092376
TI  - Plasticity of osteoprogenitor cells.
AB  - Plasticity is the ability to give rise to cell types whose phenotype is different
      from that of the source tissue. Osteoblasts originate in progenitors located in
      the bone marrow or around blood vessels. Marrow stromal cells can differentiate
      into adipocytes, in part at the expense of osteoblasts. The osteoblast-adipocyte
      balance is influenced by systemic factors, chiefly hormones, and local factors in
      the microenvironment, as well as by mechanical loads, which induce or suppress
      the activity of transcription factors crucial to the differentiation of each cell
      type. New insights into the molecular mechanisms involved in controlling the
      osteoblast-adipocyte balance are unlocking doors to a vast array of innovative
      treatment strategies.

PMID- 18092377
TI  - TNFalpha antagonists in rheumatoid arthritis patients seen in everyday practice.

PMID- 18092378
TI  - Early- versus late-onset shock in European intensive care units.
AB  - We investigated the possible differences in epidemiology, clinical course,
      management, and outcome between early and late occurrence of shock using data
      from the Sepsis Occurrence in Acutely Ill Patients Study, a large European
      multicenter study, which prospectively collected data from all adult intensive
      care unit (ICU) patients admitted to a participating center within a 2-week
      period in 2002. Shock was defined as hemodynamic compromise necessitating the
      administration of vasopressor agents. Early and late shock were defined as onset
      of shock within the first 2 days in the ICU or later, respectively. Of 3,147
      patients, 1,058 (33.6%) had shock at any time, of whom 462 (43.7%) had septic
      shock. Patients with late shock had a higher incidence of respiratory (87.4 vs.
      69.7%, P < 0.001) and hepatic (15.5 vs. 8.7%, P < 0.05) failure, and more often
      received dopamine (44.7% vs. 34.5%, P < 0.05) and albumin (31.1% vs. 20.3%, P <
      0.001) than patients who developed shock early. Intensive care unit and hospital
      mortality rates were greater in patients who developed shock late, rather than
      early (52.4% vs. 36.8% and 55.3% vs. 43%, respectively, P < 0.02). In a
      multivariable analysis, late shock was associated with an independent risk of
      higher ICU mortality in shock patients (odds ratio, 2.6; 95% confidence interval,
      1.6-4.3, P < 0.001). These observations have important implications in
      establishing individual prognosis as well as in the design and interpretation of
      clinical trials.

PMID- 18092379
TI  - Endogenous vasopressin and copeptin response in multiple trauma patients.
AB  - Endogenous arginine vasopressin (AVP) levels in multiple trauma patients are
      unknown. Arginine vasopressin is considered to play an important role in severe
      hemorrhage. In this prospective study, 87 multiple trauma patients (Injury
      Severity Score >15) and 50 healthy volunteers were enrolled. On admission to the
      emergency department (ED), demographic, clinical, and laboratory data were
      documented, and blood was sampled for determination of AVP (radioimmunosassay)
      and copeptin, a stable fragment of the AVP precursor (immunoluminometric assay).
      In patients requiring intensive care unit (ICU) therapy, blood and data sampling
      were repeated at 4, 6, and 24 h after ED admission. Linear logistic and mixed
      effects regression analyses were used for statistical analysis. On ED admission,
      AVP plasma concentrations (43.2 +/- 84.9 pM) were significantly increased when
      compared with controls (0.92 +/- 0.44 pM, P < 0.001). Plethysmographic oxygen
      saturation was the only parameter independently associated with AVP (regression
      coefficient, -0.126; 95% confidence interval, -0.237 to -0.014; P = 0.03). No
      correlation was observed between AVP and survival (P = 0.62), hemodynamic
      variables (systolic arterial pressure, P = 0.24; MAP, P = 0.59; diastolic
      arterial pressure, P = 0.74; central venous pressure, P = 0.36), or brain trauma
      (P = 0.46). In ICU patients, AVP decreased during the first 24 h (P < 0.001) and
      was independently associated with heart rate (P = 0.02) and blood glucose (P =
      0.009). Copeptin concentrations were correlated with AVP (r2 = 0.718, P < 0.001).
      In conclusion, AVP was significantly increased in multiple trauma patients and
      seems to be an integral part of the neuroendocrine response to severe injury. In
      ICU patients, AVP decreased to moderately elevated levels within 24 h after ED
      admission.

PMID- 18092381
TI  - Endotoxin impairs the human pacemaker current If.
AB  - LPSs trigger the development of sepsis by gram-negative bacteria and cause a
      variety of biological effects on host cells, including alterations on ionic
      channels. Because heart rate variability is reduced in human sepsis and
      endotoxemia, we hypothesized that LPS affects the pacemaker current I(f) in human
      heart, which might--at least in part--explain this phenomenon. Isolated human
      myocytes from right atrial appendages were incubated for 6 to 10 h with LPS (1
      and 10 microg/mL) and afterwards used to investigate the pacemaker current I(f).
      I(f) was measured with the whole-cell patch-clamp technique (at 37 degrees C).
      Incubation of atrial myocytes with 10 microg/mL LPS was found to significantly
      impair I(f) by suppressing the current at membrane potentials positive to -80 mV
      and slowing down current activation, but without effecting maximal current
      conductance. Furthermore, in incubated cells (10 microg/mL), the response of I(f)
      to [beta]-adrenergic stimulation (1 microM isoproterenol) was significantly
      larger compared with control cells (shift of half-maximal activation voltage to
      more positive potentials amounted to -10 and -14 mV in untreated and treated
      cells, respectively). Simulations using a spontaneously active sinoatrial cell
      model demonstrated that LPS-induced I(f) impairment reduced the responsiveness of
      the model cell to fluctuations of autonomic input. This study showed a direct
      impact of LPS on the cardiac pacemaker current I(f). The LPS-induced I(f)
      impairment may contribute to the clinically observed reduction in heart rate
      variability under septic conditions and in cardiac diseases such as heart
      failure, where endotoxin can be of pathophysiological relevance.

PMID- 18092380
TI  - Admission angiopoietin levels in children with septic shock.
AB  - Angiopoietin (angpt) 1 and angpt-2 are circulating proteins first ascribed
      opposing roles in embryonic angiogenesis. Both bind the tyrosine kinase with
      immunoglobulin-like loop and epidermal growth factor homology domains (Tie) 2
      receptor on endothelial cells, but angpt-1 is a Tie-2 agonist, whereas angpt-2
      antagonizes Tie-2 signaling. In the developed vasculature, angpt-1 protects
      against vascular leak, whereas angpt-2 promotes increased vascular permeability.
      Because alterations in vascular permeability are common in septic shock, we
      obtained plasma from critically ill children within 24 h of diagnosis of the
      systemic inflammatory response syndrome (SIRS, n = 20), sepsis (n = 20), or
      septic shock (n = 61), as well as 15 healthy controls. Plasma levels of angpt-1
      and angpt-2 were measured via a commercially available enzyme-linked
      immunosorbent assay. Plasma angpt-2 levels were significantly elevated in
      children with septic shock when compared with healthy children, as well as
      critically ill children with either SIRS or sepsis, and circulating angpt-2
      levels seemed to correlate with disease severity and outcome. In addition, plasma
      angpt-1 levels were significantly decreased in critically ill children with
      septic shock compared with critically ill children with either SIRS or sepsis.
      Given the contrasting effects of angpt-2 and angpt-1 on the vascular endothelium,
      these two factors may play an important role in the pathophysiology of septic
      shock in children, and further studies are warranted.

PMID- 18092382
TI  - Cortisol in severely burned patients: investigations on disturbance of the
      hypothalamic-pituitary-adrenal axis.
AB  - Thermal injuries of more than 20% of body surface area lead to conditions
      resembling a severe systemic inflammatory response syndrome, such as in septic
      shock. It has been shown that septic shock may lead to disturbances in cortisol
      metabolism and balance of the hypothalamic-pituitary-adrenal axis. To investigate
      whether such a disturbance also occurs in the very early stages of systemic
      inflammatory response syndrome in burned patients, we performed 20 corticotropin
      releasing hormone tests on day 1 after admission to our unit. In 7 of 20
      patients, a disturbance of cortisol secretion could be demonstrated. Four
      patients developed adrenal insufficiency. The correlation between the abbreviated
      burn severity index and the risk of developing adrenal insufficiency was
      significant (P = 0.008). We observed a higher mortality rate in adrenally
      insufficient patients; however, because of the small patient number, we were not
      able to prove this observation with a statistical significant correlation (P =
      0.11). Our findings indicate that temporary adrenal insufficiency occurs in the
      early stages of severe injury. Further investigations will have to be performed
      to clarify whether such patients benefit from cortisol replacement.

PMID- 18092383
TI  - Clinical and pathologic manifestations of necrobiosis lipoidica-like skin
      involvement in sarcoidosis.
AB  - Necrobiosis lipoidica dibeticum (NLD) is a granulomatous skin disease mostly
      associated with diabetes mellitus. NLD has been reported in patients with other
      systemic disease. Also, the lesions of NLD may be clinically, and sometimes even
      histologically indistinguishable from other inflammatory skin lesions. We
      described three patients with established diagnosis of sarcoidosis that developed
      skin lesions consistent with NLD. The association of NLD-like skin lesion in
      sarcoidosis is not widely appreciated. The subject of NLD and sarcoidosis is
      reviewed.

PMID- 18092385
TI  - A view from Belgium: Guy Berkenboom, MD, PhD, FESC. Interview by Barry Shurlock.

PMID- 18092384
TI  - Early versus late onset of multiple organ failure is associated with differing
      patterns of plasma cytokine biomarker expression and outcome after severe trauma.
AB  - Although multiple organ failure (MOF) remains the leading cause of death after
      trauma, the pathogenic cellular and molecular mechanisms underlying MOF are
      poorly understood. In addition to proinflammatory and anti-inflammatory mediator
      cascades, the temporal onset of MOF has generated recent interest because the
      organ systems involved into MOF seem to deteriorate in a time-dependent fashion
      after trauma. We therefore investigated the temporal course of MOF in traumatized
      human patients and evaluated and compared the distribution patterns of cytokine
      expression, including interleukin (IL) 6, IL-8, IL-10, and the soluble tumor
      necrosis factor-[alpha] receptors sTNF-R p55 and sTNF-R p75 in early-onset versus
      late-onset MOF. In addition, we analyzed the predictive value of cytokine
      biomarkers of MOF and lethal outcome. In a prospective observational cohort study
      conducted at three trauma centers, all patients (n = 352) admitted to two level 1
      trauma centers in Germany were enrolled in the study based on the following
      inclusion criteria: severe traumatic brain injury (TBI) with a Glasgow Coma Scale
      (GCS) score of 8 or lower and/or distinct changes in cranial computed tomography
      and/or multiple injuries (MT) to the body (at least two regions had Abbreviated
      Injury Scale score of 3 or higher). The incidence of MOF was evaluated using the
      modified Goris-MOF score. The temporal onset of MOF was divided into early-onset
      MOF (EMOF, developing on days 0-3), late-onset MOF (LMOF, developing on days 4
      10), combined early-onset and late-onset MOF (CMOF), and patients never showing
      signs of MOF during the observation period. In addition, the levels of the serum
      cytokine markers IL-6, IL-8, IL-10, sTNF-R p55, and sTNF-R p75 were analyzed at
      specific posttraumatic time points using established enzyme-linked immunosorbent
      assay techniques. A total of 352 patients (274 men and 78 women; TBI, 101; TBI +
      MT, 125; MT, 126) were enrolled into the study. Patients assigned to the EMOF
      group showed specific disruption of pulmonary and cardiocirculatory function,
      whereas LMOF was significantly associated with hepatic failure. The patients
      without signs of MOF and the EMOF patients had the same risk of lethal outcome
      (8.2% vs. 7.5%); LMOF and CMOF were found to be associated with a 3- to 4-fold
      increase in mortality (38.5% vs. 30.6%, respectively). Analysis of cytokine serum
      biomarkers revealed that patients with LMOF showed a biphasic elevation of IL-6
      and significantly higher sTNF-R concentrations than did all other subgroups (P <
      0.001). In addition, the initial values (days 0-1) of sTNF-R p55 and sTNF-R p75
      expression levels had a good predictive capacity for the development of LMOF
      (p55, 0.75; p75, 0.72); values greater than 0.65 were accepted to have a
      predictive capacity. These results demonstrate that mortality differs
      significantly between the development of EMOF and LMOF after traumatic injury.
      Our results also suggest that serum cytokine measurements may be important early
      biochemical markers for predicting the development of delayed MOF.

PMID- 18092386
TI  - A blow to the herbalists.

PMID- 18092387
TI  - Reflections on Loewald's "Internalization, separation, mourning, and the
      superego".

PMID- 18092388
TI  - Principles of protein and lipid targeting in secondary symbiogenesis: euglenoid,
      dinoflagellate, and sporozoan plastid origins and the eukaryote family tree.
AB  - The biggest unsolved problems in chloroplast evolution are the origins of
      dinoflagellate and euglenoid chloroplasts,which have envelopes of three membranes
      not two like plants and chromists, and of the sporozoan plastid, bounded by four
      smooth membranes. I review evidence that all three of these protozoan plastid
      types originated by secondary symbiogenesis from eukaryotic symbionts. Instead of
      separate symbiogenetic events, I argue that dinoflagellate and sporozoan plastids
      are directly related and that the common ancestor of dinoflagellates and Sporozoa
      was photosynthetic. I suggest that the last common ancestor of all Alveolata was
      photosynthetic and acquired its chlorophyll c-containing plastids in the same
      endosymbiogenetic event as those of Chromista. Chromistaand Alveolata are
      postulated to be a clade designated chrornalveolates. I propose that euglenoids
      obtained their plastids from the same(possibly ulvophycean) green alga as
      chlorarachneans and that Discicristata (Euglenozoa plus Percolozoa) and Cercozoa
      (the group including chlorarachneans) form a clade designated cabozoa (protozoa
      with chlorophyll a + b). If both theories are correct, there were only two
      secondary symbiogenetic events (witnessed by the chlorarachnean and cryptomonad
      nucleormorphs) in the history of life, not seven as commonly assumed. This
      greatly reduces the postulated number of independent origins of chloroplast
      protein-targeting machinery and of gene transfers from endosymbiont to host
      nuclei. I discuss the membrane and plastid losses and innovations in protein
      targeting implied by these theories, the comparative evidence for them, and their
      implications for eukaryote megaphylogeny. The principle of evolutionary
      conservatism leads to a novel theory for the function of periplastid vesicles in
      membrane biogenesis ofchlorarachneans and chromists and of the key steps in
      secondary symbiogenesis. Protozoan classification is also slightly revised by
      abandoning the probably polyphyletic infrakingdom Actinopoda, grouping
      Foraminifera and Radiolaria as a new infrakingdom Retaria,placing Heliozoa within
      a revised infrakingdom Sarcomastigota, establishing a new flagellate phylum
      Loukozoa for Jakobea plus Anaeromonadea within an emended subkingdom Eozoa, and
      ranking Archezoa as an infrakingdom within Eozoa.

PMID- 18092389
TI  - Additional information on melamine in pet food.

PMID- 18092390
TI  - Lady Osler Endowment.
AB  - Discusses the financing of activities and book purchases by the Osler Library of
      McGill University through an endowment from Grace Linzee, Lady Osler.

PMID- 18092391
TI  - Sir William and the Osler Library's Board of Curators.

PMID- 18092392
TI  - Mission: delivering preventive medicine.

PMID- 18092393
TI  - Community health centers tackle rising demands and expectations.
AB  - As key providers of preventive and primary care for underserved people, including
      the uninsured, community health centers (CHCs) are the backbone of the U.S.
      health care safety net. Despite significant federal funding increases, community
      health centers are struggling to meet rising demand for care, particularly for
      specialty medical, dental and mental health services, according to findings from
      the Center for Studying Health System Change's (HSC) 2007 site visits to 12
      nationally representative metropolitan communities. Health centers are responding
      to these pressures by expanding capacity and adding services but confront
      staffing, resource and other constraints. At the same time, CHCs are facing other
      demands, including increased quality reporting expectations, addressing racial
      and ethnic disparities, developing electronic medical records, and preparing for
      public health emergencies.

PMID- 18092394
TI  - The invisible farmer? Women, gender, and colonial agricultural policy in the Igbo
      region of Nigeria, c. 1913-1954.

PMID- 18092395
TI  - The use of the Patient Health Questionnaire--9 Korean Version (PHQ-9K) to screen
      for depressive disorders among Korean Americans.

PMID- 18092396
TI  - "Are you going to be Miss (or Mr) Africa?" Contesting masculinity in Drum
      magazine.
AB  - Drum magazine was first published in March 1951. Like other magazines, it both
      reflected and shaped the society from which its audience emerged. During 1951,
      its audience, mainly urban black readers, was able to push the publication away
      from its original rural focus towards an urban emphasis. Town living, however,
      meant different things to different people. Thus, while readers were successful
      in shifting the focus of the magazine, they were less successful in influencing
      the way the publication presented urban life. This paper explores the struggle
      between readers, journalists and editors over the Miss Africa beauty contest
      announced at the beginning of 1952. Although the magazine reluctantly admitted
      men to the contest, it discriminated against male entrants in a variety of ways
      over the course of the year, and subsequent competitions barred male contestants
      entirely. Despite opposition from male readers who wished to be considered
      beautiful, the men of Drum were largely successful in asserting their own deeply
      gendered cultural vision of urban life.

PMID- 18092397
TI  - The courage of Galileo: Joseph Needham and the "germ warfare" allegations in the
      Korean War.

PMID- 18092398
TI  - Dr. Casey Wood and the McGill Medical Libraries.

PMID- 18092399
TI  - The Osler catalogue.

PMID- 18092400
TI  - Paliperidone: new drug. Just a metabolite of risperidone, a neuroleptic soon off
      patent.
AB  - (1) For patients with schizophrenia, risperidone is one of many available
      neuroleptics. It has no tangible advantages over conventional neuroleptics such
      as haloperidol. (2) Paliperidone, the main active metabolite of risperidone, has
      now arrived on the European market, in the form of sustained-release osmotic
      tablets. Clinical evaluation is based on 3 placebo-controlled trials lasting 6
      weeks. As expected, paliperidone was effective in relieving symptoms of
      schizophrenia. However, it was no more effective than olanzapine and has not been
      compared with risperidone. (3) The adverse effect profile of paliperidone in
      these trials was predictable, consisting mainly of short-term neurological
      effects and dose-dependent weight gain. Paliperidone also provokes tachycardia
      and lengthens the QT interval in some patients. The rigid osmotic tablets can
      cause gastrointestinal complications. (4) Paliperidone does not represent a
      therapeutic advance. It is better to continue using a conventional neuroleptic
      such as haloperidol.

PMID- 18092401
TI  - A note from NIDA's director. Images and interventions.

PMID- 18092402
TI  - The Rosencrantz Collection of Osleriana, San Francisco.

PMID- 18092403
TI  - Clofarabine: new drug. Children with acute lymphoblastic leukaemia: a last
      resort.
AB  - (1) Standard treatments fail in about 20% of children with acute lymphoblastic
      leukaemia. About half these children die within 10 weeks. (2) Clofarabine, a
      cytotoxic drug chemically related to fludarabine, is now marketed for use in this
      setting. (3) The decision to grant marketing authorization was based mainly on
      the results of a non comparative trial including 61 patients aged from 1 year to
      20 years who had few if any other therapeutic options. The median survival time
      was 13 weeks overall, but about 70 weeks in the subgroup of children who had a
      full haematological response (20% of the study population). About half these
      latter patients were able to undergo potentially curative haematopoietic stem
      cell transplantation. (4) Preliminary results from another non comparative trial
      suggest similar efficacy. (5) Short-term adverse effects are frequent and often
      serious, and include gastrointestinal disorders, infections, tumour lysis
      syndrome, and cardiac, renal and hepatobiliary disorders. The latter effects had
      also occurred in animal studies. (6) These results warrant further studies,
      especially to identify those children most likely to benefit from clofarabine. In
      the meantime, this last-chance treatment can sometimes create the conditions for
      potentially curative therapy.

PMID- 18092404
TI  - Alglucosidase alfa: new drug. Pompe disease: a short-term benefit.
AB  - (1) Pompe disease is the early-onset form of type 2 glycogenosis, a rare enzyme
      deficiency. Onset occurs in early infancy, and most patients die from
      cardiorespiratory failure before their first birthday. (2) The missing enzyme,
      alglucosidase alfa is now produced through biotechnology and is approved as
      replacement therapy for infants with Pompe disease. (3) According to a dose
      finding study involving 19 infants, and a somewhat shaky historical comparison,
      alglucosidase alfa has a positive impact on survival at the age of 18 months. (4)
      The main known adverse effects of alglucosidase alfa are potentially severe
      infusion reactions and the development of anti-alglucosidase antibodies. (5)
      Treatment requires an intravenous infusion every two weeks. In France, it costs
      4200 euros for a child weighing 10 kg. (6) Alglucosidase alfa replacement therapy
      is the only treatment that seems to improve the short-term survival of infants
      with Pompe disease. However, it should only be used within a context of continued
      assessment.

PMID- 18092405
TI  - Intra-articular triamcinolone: new indication. Juvenile idiopathic arthritis:
      several months of relief.
AB  - Effective in more than three-quarters of children for at least 6 months after the
      injection. Caution about the risk of systemic adverse effects, especially in
      cases of repeated use.

PMID- 18092406
TI  - W. W. Francis, patron of the Osler Society.
AB  - Address delivered by E. H. Bensley of the Department of the History of Medicine
      at the Fiftieth Anniversary Commemorative Banquet of the Osler Society of McGill
      University, April 1, 1971.

PMID- 18092407
TI  - Leuprorelin, triptorelin: new indications. Locally advanced prostate cancer:
      minimally assessed me-toos.
AB  - Unlike goserelin, leuprorelin and triptorelin have not been assessed for their
      impact on survival in patients with locally advanced prostate cancer. The main
      adverse effects of these two drugs are similar, but convenience of use differs.

PMID- 18092408
TI  - The Fortsas catalogue.
AB  - Examines two items in Sir William Osler's Bibliotheca Osleriana, both relating to
      the Fortsas library sale hoax of 1840.

PMID- 18092409
TI  - Ibuprofen: new indication. Migraine attacks: don't begin with 400 mg!
AB  - Ibuprofen, initially at a dose of 200 mg, is a second-line option for treating
      migraine attacks after paracetamol fails.

PMID- 18092410
TI  - Norman Bethune and his friends.

PMID- 18092411
TI  - Sir William Osler and William Williams Keen.

PMID- 18092412
TI  - The Osler Library Reception Committee (1920-1928).

PMID- 18092413
TI  - The architect of the first Osler Library: Percy Erskine Nobbs.

PMID- 18092414
TI  - Tigecycline.
AB  - Complicated cutaneous and intra-abdominal infections: no progress.

PMID- 18092415
TI  - The age of acupuncture.

PMID- 18092416
TI  - Aluminium-containing transdermal patches: a risk of burns.
AB  - (1) The waterproof outer layer protecting some transdermal patches is composed of
      aluminium. This creates a risk of burns, especially when the patient is exposed
      to electric shocks or intense magnetic fields. (2) External electrical shocks
      delivered by a defibrillator for example can create electrical arcing between the
      electrode and the aluminium layer of the patch, potentially causing burns. (3)
      During Magnetic Resonance Imaging (MRI) the aluminium present in these patches,
      which is not ferromagnetic, creates electrical resistance (by induction), and can
      sometimes cause second-degree burns. (4) Patients undergoing MRI or
      defibrillation should first be examined for patches containing aluminium. Such
      patches can generally be identified by examining the backing, which is shiny and
      reflects light if aluminium is present. (5) If in doubt it is best to temporarily
      remove all transdermal patches before MRI or external defibrillation. (6)
      Packaging of transdermal patches that contain conductive materials should include
      more explicit warnings.

PMID- 18092417
TI  - Peripheral neuropathy and statins.
AB  - (1) Statins are cholesterol-lowering drugs extensively used in cardiovascular
      prevention. Their most well-known adverse effect is muscle damage, including
      rhabdomyolysis. (2) Several cases of peripheral polyneuropathy attributed to a
      statin have been published or reported by pharmacovigilance centres. (3) They
      included sensory or sensorimotor polyneuropathy with signs of sensory impairment,
      and a decrease or sometimes a suppression of osteotendinous reflexes. Some
      patients also had a marked reduction in muscle strength in the affected limb(s).
      Renal failure and diabetes appear to increase the risk of this adverse effect.
      (4) Epidemiological studies and clinical trials have shown that this adverse
      effect is rare, affecting only about one patient in 10 000 treated for one year.
      (5) After ruling out other possible causes of peripheral neuropathy, statin
      withdrawal often leads to clinical improvement.

PMID- 18092418
TI  - The Open Arms.
AB  - Description of The Open Arms, Sir William Osler's residence when he lived in
      Oxford beginning in 1905.

PMID- 18092419
TI  - Books for horsemen in the Bibliotheca Osleriana.

PMID- 18092420
TI  - Levonorgestrel-releasing intrauterine device and uterine perforations.
AB  - Cases of uterine perforation have been reported with levonorgestrel-releasing
      intrauterine devices, possibly linked to their large size; the incidence seems to
      be similar to that observed with non-drug intrauterine devices.

PMID- 18092421
TI  - Topical tacrolimus plus oral alcohol: skin irritation.
AB  - (1) In clinical trials of topical tacrolimus (an immunosuppressant), transient
      skin irritation, usually at the site of application, occurred in about 0.5% to
      1.3% of adult patients who had also ingested ethyl alcohol. This adverse effect
      has also been observed with topical pimecrolimus, a related drug. (2) Three
      paediatric cases have also been published. The alcohol they ingested was one of
      the excipients of an oral drug. (3) If skin irritation occurs at the application
      site for topical tacrolimus, the role of ethyl alcohol, which may have been used
      as an excipient for a co-administered oral drug, should be borne in mind.

PMID- 18092422
TI  - Rimonabant: suicide and depression. Depression and suicidal tendencies are about
      twice as frequent with rimonabant as with placebo.

PMID- 18092423
TI  - LMWH and renal failure: bleeding. Creatinine clearance should be checked before
      choosing heparin products.

PMID- 18092424
TI  - Chinese translations of Western medical textbooks.

PMID- 18092425
TI  - Multiple sclerosis: interferon beta for some serious forms.
AB  - (1) Multiple sclerosis is a neurological disorder characterised by disseminated
      inflammatory lesions of the myelin sheath, the white fatty layer that covers the
      neurons in the brain and spinal column. The clinical repercussions are highly
      variable, ranging from minor deficits to severe disability and even death. Some
      patients have exacerbations separated by remissions of varying length, while
      others experience fairly steady progression of disability. This review article,
      based on Prescrire's standard in-house methodology, examines treatments proposed
      to slow the progression of multiple sclerosis. (2) For exacerbations (4 trials, a
      total of 140 patients), an improvement was noted in 64% of patients treated with
      intravenous methylprednisolone for 5 days, versus 40% of patients on placebo. (3)
      Interferon beta is the best-assessed of the disease-modifying drugs. Various
      marketed interferon beta products have been compared with one another in trials
      involving more than 1000 patients in total. There are no major differences in
      effectiveness or adverse effects. The latter are frequent, especially a flu-like
      syndrome and depression. (4) After a first episode suggestive of multiple
      sclerosis (3 trials, a total of 1160 patients), 35% of patients treated with
      interferon beta subsequently developed the disease, versus 50% of patients in the
      placebo groups. This advantage seemed to persist for at least 8 years. (5) In
      relapsing-remitting multiple sclerosis (4 trials, a total of 1426 patients),
      interferon beta prevented about one exacerbation every 2.5 to 3 years but had no
      clear preventive impact on progression of disability. (6) In secondary
      progressive multiple sclerosis (5 trials, a total of 3082 patients), interferon
      beta's effectiveness, if present, was limited to patients who continued to have
      exacerbations. (7) Natalizumab does not appear to be more effective than
      interferon beta. It is associated with serious adverse effects, about which only
      limited information is available. (8) Glatiramer has not been shown to prevent
      exacerbations or progression of disability. Intravenous immunoglobulin is still
      being tested in multiple sclerosis. In initially aggressive forms of multiple
      sclerosis, mitoxantrone has a negative risk-benefit balance (2 trials, 236
      patients); it prevents less than one exacerbation during two years of treatment
      but causes heart failure in 1% to 2% of patients after 10 months of treatment.
      (9) Patients' anxiety as their disability worsens must not overshadow the fact
      that there are no treatments available with strong clinical effectiveness, and
      that all existing treatments carry a risk of serious adverse effects. Pending the
      arrival of something better, only interferon beta has a favourable risk-benefit
      balance, and only in selected patients.

PMID- 18092426
TI  - COPD: don't use fluticasone + salmeterol. Patients treated with inhaled
      fluticasone for chronic obstructive pulmonary disease (COPD) are more prone to
      pneumonia.

PMID- 18092427
TI  - Elderly patients with dementia: towards less neuroleptic use. Behavioural
      management can help to reduce neuroleptic use.

PMID- 18092428
TI  - LH/FSH ratio: a better marker of secondary amenorrhea in patients from eastern
      Nepal.
AB  - FSH, LH and prolactin (PRL) levels were assessed by ELISA in 50 cases with
      secondary amenorrhea and 52 age and sex-matched healthy controls from eastern
      Nepal. Cases were diagnosed by differential diagnosis, and data were analyzed
      using standard statistical tools. Early stage (3-6 months) and long standing (> 6
      months) secondary amenorrhea had no effect (p > 0.05) in hormonal parameters
      studied. Pulse, SBP, DBP, weight, height, age of menarche, cycle interval and
      duration of flows were homogenous (p > 0.05) in patients and controls. Median age
      of menarche, median cycle interval and median duration of flows in healthy
      subjects were 14 years, 30 and 4 days respectively. FSH in cases (15.38 +/- 7.24
      mU/ml) was significantly elevated (p < 0.01) as compared to controls (9.38 +/-
      6.34 mU/ml). LH in cases (35.44 +/- 24.35 mU/ml, median 36.5 mU/ml) was
      significantly (p < 0.01) elevated by almost 5 times of its mean value and 9 times
      of its median value as compared to that of controls (7.58 +/- 6.604 mU/ml, median
      4.2 mU/ml). LH/ FSH ratio in cases (2.44 +/- 1.73, median 2.00) was significantly
      higher (p < 0.01) as compared to controls (0.82 +/- 0.42, median 0.76). FSH e"12
      mU/ml, LH e"10 mU/ml and LH/FSH ratio e"1 cut offs were significantly associated
      (p = 0.000 in each) with the cases as revealed by chi-square analysis, and LH/FSH
      ratio e"1 (Sensitivity = 84.0%, specificity = 77.0%) was found to be a stronger
      marker of secondary amenorrhea. As the elevation of LH was more pronounced than
      that of FSH, this study hints towards possible LH receptor mutation, which is
      generally found in premature ovarian failure (POF). Diagnosis of cases in this
      region may need a new cut off level for POF, as the elevation of FSH itself was
      not as pronounced as reported by other workers.

PMID- 18092429
TI  - The prevalence of type 2 diabetes mellitus and impaired fasting glucose in semi
      urban population of Nepal.
AB  - The increase in life expectancy in developing countries and as a result of
      increasing obesity and other life style changes, the global incidence of type 2
      diabetes mellitus (T2DM) is increasing. The purpose of this study was to
      investigate the prevalence of T2DM and impaired fasting glucose (IFG) in semi
      urban population of Nepal and to compare the prevalence between men and women and
      among different age groups. A total 740 adults (286 men and 454 women) aged 21 to
      94 years (men +/- SD; 45.6 +/- 15.6 years) were included. The prevalence of T2DM
      and IFG was 9.5% and 19.2% in the whole population. Prevalence of T2DM was higher
      in men (11.8%) then in women (7.9%), similarly IFG was noted higher in men (25%)
      then in women (15.4%0). The prevalence of T2DM and IFG was seen to be increased
      with age in the whole population. Among women, the prevalence of T2DM and IFG was
      2.9% and 12.8% in 21 to 40 years age group, 9.7% and 13.8% in 41 to 60 years age
      group and 15.4% and 27.7% in > 60 years age group. Among men, it was 4.7% and
      22.6% in 21 to 40 years age group, 13.3% and 30.5% in 41 to 60 years age group
      and 23% and 17.3% in > 60 years age group. To conclude, the overall prevalence of
      T2DM and IFG increases with age. Prevalence of IFG is highest among middle age
      men where as the prevalence of T2DM is highest among older men.

PMID- 18092430
TI  - An evaluation of training of teachers in medical education in four medical
      schools of Nepal.
AB  - Effective teaching is a concern of all teachers. Therefore, regular teachers'
      training is emphasized globally. B. P. Koirala Institute of Health Sciences
      (BPKIHS), a health science deemed university situated in eastern region of Nepal
      has an established Medical Education unit which attempts to improve teaching
      learning skills by training faculty members through organizing regular medical
      education training programs. The aim of the present study was to assess the
      effectiveness of 3-day training workshop on "Teaching-learning methodology and
      Evaluation" held in four different medical colleges of Nepal. The workshop was
      targeted at middle and entry level of health profession teachers who had not been
      previously exposed to any teacher's training program. The various components,
      such as teaching-learning principles, writing educational objectives, organizing
      and sequencing education materials, teaching-learning methods, microteaching and
      assessment techniques, were incorporated in the workshop. A team of resource
      persons from BPKIHS were involved in all the four medical institutions. The
      collection data had two categories of responses: (1) a questionnaire survey of
      participants at the beginning and end of the workshop to determine their gain in
      knowledge and (2) a semi-structured questionnaire survey of participants at the
      end of workshop to evaluate their perception on usefulness of the workshop. The
      later category had items with three-point likert scale (very useful, useful and
      not useful) and responses to open-ended questions/ statements to document
      participants general views. The response was entered into a spreadsheet and
      analyzed using SPSS. The result showed that all participants (n = 92) improved
      their scores after attending the workshop (p < 0.001). Majority of respondents
      expressed that the teaching-learning methods, media, microteaching and evaluation
      techniques were useful in teaching-learning. The workshop was perceived as an
      acceptable way of acquiring teaching-learning skills but 39.4% participants
      expressed that the duration of the workshop was too short. The overall impression
      about trainers was very positive. Therefore, regular organization of such
      workshops with addition of new advances in medical education would be highly
      beneficial to improve teaching learning skill of medical teachers.

PMID- 18092431
TI  - HilA gene expression in SCFAs adapted and inorganic acid challenged Salmonella
      enterica serovar typhimurium.
AB  - Salmonella enterica serovar typhimurium (S. typhimurium) encounters short chain
      fatty acids (inorganic acids containing propionate, butyrate and acetate) in the
      intestine as well as in food preservatives. Short chain fatty acids (SCFAs)
      exposed organisms have been reported to offer resistance to organic acid
      resulting into enhanced virulence. However, the role of hilA (hyper invasive
      loci) gene expression has not been assessed in this context. In the present
      study, S. typhimurium was grown under SCFAs stress condition simulating the in
      vivo environment and hilA gene expression was evaluated. The gene expression was
      measured by beta-galactosidase (beta-gal) assay using a hilA-lacZY fusion strain
      and calculated as Miller units. hilA gene expression was found to be
      significantly higher in the SCFAs exposed cells than the unexposed ones, after 2
      hrs and 4 hrs of exposure. However, no significant difference was observed
      between the activities at 2 hrs and 4 hrs. It indicates that hilA gene gets
      expressed by 2 hrs and persists till 4 hrs at least. The beta-gal activity was
      also measured in the unadapted / SCFAs adapted organisms followed by acid shock
      for 1 hr. The gene expression was also found to be higher in the SCFAs adapted-
      acid (pH 3) challenged as compared to the unadapated acid challenged organisms
      suggesting that SCFAs adaptation may induce organic acid tolerance by modulating
      the hilA response. This observation indicates that hilA may be the additional
      gene contributing to acid resistance and thereby increasing virulence of the
      organism after SCFAs adaptation.

PMID- 18092432
TI  - Soil transmitted helminthiasis in Kathmandu, Nepal.
AB  - A total of 200 soil samples taken from different sites and 1,504 stool samples
      collected from school children (n = 188) and patients (n = 1,316) visiting the
      health care centres in Kathmandu Valley were included in this study. Soil samples
      were investigated for the presence of parasitic eggs using sucrose flotation
      technique. Stool samples were examined by formal-ether concentration and direct
      smear techniques. The contamination rate of soil with parasitic eggs and larvae
      was found to be 28.5% (57/ 200). The overall parasitic infection rates in school
      children and patients were 42.5% and 2.8%, respectively. Four types of parasites
      were detected from soil samples, of which Ascaris was the most common. Trichuris
      was most common among school children whereas Ascaris in patients. Females in
      both study groups had higher prevalence compared with male counterparts with
      significantly low rate in health care centre visiting patients (p < 0.05).

PMID- 18092433
TI  - Antibiotic susceptibility pattern of urinary isolates in Imphal (Manipur), India.
AB  - The present study was conducted to detect aerobic causative agents of urinary
      tract infection (UTI) and their antibiogram pattern. This study was carried out
      in the Department of Microbiology, Regional Institute of Medical Sciences (RIMS),
      Imphal, Manipur, India. A total of 1,109 clean catched midstream urine samples
      were collected, out of which 459 (40.4%) samples grew potential pathogens causing
      UTI. Escherichia coli were the predominant 334 (72.8%) bacterial pathogen
      followed by Klebsiella species 66 (14.4%), non lactose fermenters 19 (4.1%),
      Pseudomonas species 16 (3.5%) and others. Most of the strains of E. coli were
      resistance to Ciprofloxacin whereas sensitive to Aminoglycoside. Most of the
      urinary isolates showed high degree of resistance to Tetracycline, Norfloxacin
      and Cotrimoxazole. Gentamycin was the drug of choice for most of the strains.

PMID- 18092434
TI  - Comparison of endoscopic findings in patients from different ethnic groups
      undergoing endoscopy for upper gastrointestinal bleed in eastern Nepal.
AB  - Upper gastrointestinal (UGI) bleed is one of the commonest medical emergencies.
      Cultural customs and practices may influence the development of disease
      conditions that may lead to UGI bleed. The purpose of this study was to compare
      the causes of UGI bleed in different ethnic groups among patients presenting to a
      large tertiary care hospital with acute UGI bleed. A retrospective study was
      conducted examining data available in the endoscopy register at the B. P. Koirala
      Institute of Health Sciences (BPKIHS) in Nepal for patients presenting with UGI
      bleed over one calendar year. Study subjects were categorized into one of a few
      broad categories of ethnic groups: Khas, Newar, SeTaMaGuRaLi, Maithali and
      others. Demographic information and endoscopic diagnoses were abstracted. The
      relative frequencies of different causes of UGI bleed were compared across the
      ethnic groups using the chi2 test. One hundred and eighty-nine patients underwent
      endoscopy for UGI bleed in the time period studied. The mean age of the study
      cohort was 49.6 years and consisted of 71.0% males and 29.0% females. Overall the
      commonest cause of upper GI bleed was gastric ulcer. Esophageal varices was the
      commonest cause in the SeTaMaGuRaLi group, accounting for 33.3%. The relative
      frequency of esophageal varices as the cause of upper GI bleed was statistically
      significantly different among the various ethnic groups, with the SeTaMaGuRaLi
      group having the highest relative frequency (p-value 0.02). Physicians taking
      care of patients with upper GI bleed in Nepal should be aware of the high
      relative frequency of esophageal varices as a cause of upper GI bleed, and
      especially so among certain ethnic groups.

PMID- 18092435
TI  - Influence of umbilical vein oxytocin on blood loss and length of third stage of
      labour.
AB  - In this study the effect of intraumbilical vein oxytocin on duration and amount
      of blood loss in third stage of labour was studied. Pregnant women were
      randomized into two groups of fifty each. Study group was managed with 10 units
      of oxytocin diluted with 10 ml of normal saline given through umbilical vein
      while control group was managed with 10 units of oxytocin in 500 ml of normal
      saline through intravenous infusion after delivery of the baby. The mean blood
      loss in the third stage of labour was 143.30 ml for the control group and 151.43
      ml for the study group while the duration of the third stage of labour was 6.02
      and 5.42 minutes for each group. There was no significant difference in the
      duration and amount of blood loss between the two groups.

PMID- 18092436
TI  - Intranasal midazolam Vs ketamine as premedication in paediatric surgical
      procedure for child separation and induction.
AB  - In children pre-anaesthetic medications are frequently administered as
      pharmacological adjunctions to help alleviate the stress and fear of surgery as
      well as to ease child parental separation and promote a smooth induction. Oral,
      rectal, intravenous and intramuscular route has been used; however each route has
      its disadvantage. Pre-anaesthetic medication administered intranasal for
      avoidance of painful injection have made it a convenient way to pre-medication.
      To evaluate the efficacy of intranasal administered Midazolam 0.2 mg/kg and
      Ketamine 5 mg/kg respectively. Total 50 patients of ASA I and II of age group 1-
      7 years, mean age 3.88 +/- 1.26 and 4.56 +/- 1.21 were included in group I and
      group II respectively, and Scheduled for elective surgery. Mean time of
      separation was 17.12 +/- 1.21 in-group I and 15.68+11.62 in group II with P value
      < 0.001 and 0.322, shows significant difference during time of separation from
      parents and no significant difference for i.v. line insertion in both groups.

PMID- 18092437
TI  - Molecular studies of E. coli mercuric reductase gene (merA) and its impact on
      human health.
AB  - Bacterial plasmids encode resistance systems for toxic metal ions including Hg2+
      functioning by energy-dependent efflux of toxic ions. The inducible mercury
      resistance (mer) operon encodes both a mercuric ion uptake and a detoxification
      enzymes. In Gram-negative bacteria especially in E. coli, a periplasmic protein,
      MerP, an inner- membrane transport protein, MerT, and a cytoplasmic enzyme,
      mercuric reductase (the MerA protein), are responsible for the transport of
      mercuric ions into cell and their reduction to elemental mercury, Hg0.
      Phytoremediation involves the use of plants to extract, detoxify and/or sequester
      environmental pollutants from soil and water. Transgenic plants cleave mercury
      ions from methyl-mercury complexes; reduce mercury ions to the metallic form;
      take up metallic mercury through their roots; and evolve less toxic elemental
      mercury. PCR were performed to detect 1695 bp of mercuric reductase gene (merA),
      which is mainly responsible for the conversion of mercuric (Hg+2) and mercurous
      (Hg+1) ions into non-toxic elemental mercury. PCR products of putative merA genes
      from environmental E. coli strains were purified and cloned into a plant
      expression vector pRT100. The construct will be transformed in calli of Nicotiana
      plants.

PMID- 18092438
TI  - Systemic lupus erythematosus in childhood--a review of 11 patients at a single
      center in eastern Nepal.
AB  - We retrospectively evaluated the clinico-laboratory features of 11 children and
      adolescents with Systemic Lupus Erythematosus between the period of 2001 and
      2006. All of them (100.0%) had renal involvement at the first visit in the
      hospital. Female to male ratio was 10:1. Skin and or mucosal involvement (90.9%),
      periorbital puffiness and or pedal edema (81.8%), fever (72.7%), hypertension
      (72.7%), and reticuloendothelial involvement (72.7%), were the commonest
      presentations. All patients had anemia (8.6 +/- 1.5 gm/dl), raised ESR (46.7 +/-
      9.4 mm in first hour), proteinuria, and in disease activity as evident by raised
      ESR and positive anti-dsDNA antibody at the first visit. The mean duration of
      disease was 7.6 months and the average duration of disease activity was 63.18
      days. Renal biopsy was performed in 8 patients: class IV lupus nephritis in 4
      patients (50.0%), class II in 2 patients (25.0%), class III and V in patient
      (12.5%) each. Nephrotic range proteinuria and hypertension was observed in all
      patients of class IV and V of lupus nephritis. Class II and III lupus nephritis
      patients' were normotensive and had non-nephrotic range proteinuria. Three out of
      11 patients (27.2%) expired. The commonest primary determinant of mortality was
      uncontrolled disease activity in 2 patients (66.6%). The third one had infection
      and developed disseminated intravascular coagulation. The mean duration of
      disease activity in patients who died (mean 30 days) was statistically lower than
      the survival group (75.6 days) (p < 0.01). Renal involvement during first visit
      and mortality could be attributed by late referrals and diagnosis at hospital.

PMID- 18092439
TI  - Assessment of pulmonary function in local healthy Nepalese men of Dharan and it's
      anthropometric correlation.
AB  - Healthy non smoking male subjects (n = 150) aged 18-40 years were subjected to
      pulmonary function testing to establish linear multiple regression model.
      Pulmonary parameters were considered as independent variables and physical
      parameters (age, height, weight, body mass index (BMI) and body surface area
      (BSA) and anthropometric parameters (skin fold thickness (SFT), mid arm
      circumference and abdominal girth) were taken as dependent variables. This study
      was undertaken to determine correlation coefficients between dependent variables
      and different pulmonary independent variables and to derive regression equations
      or prediction formulae in order to find out the expected normal values for the
      different lung function tests in a given individual. Present study revealed that
      the upper body fat distribution, as reflected by biceps skin fold thickness and
      mid arm circumference, is a significant predicator of ventilatory function.

PMID- 18092440
TI  - Microorganisms present in discharging otitis media in a group of patients in
      Kathmandu.
AB  - Discharge from the ear is one of the commonest symptoms of infections of the ear.
      To study the major strains of bacteria encountered in ear discharges, this study
      was conducted from July 1999, to June 2001 in the microbiology laboratory of Om
      Hospital. A total of 115 patients, of 6-35 years of age clinically diagnosed as
      discharging otitis media were studied. In 60.9% single organism and in 26.08% two
      organisms were isolated. Results revealed that, Staphylococcus aureus (34.3%),
      Klebsiella pneumoniae (24.3%), Pseudomons aeruginosa (22.8%), Enterobacter sps
      (7.1%), Esch coli (4.3%), Citrobacter sps (1.4%), Proteus sps (1.4%),
      Acinetobacter sps (1.4%) and Pneumococci (1.4%) were the common organisms in the
      discharge. Candida albicans (2.8%) was the pathogen in two cases. In 27.8% of
      cases the causative agent was not demonstrated. About sixty percent (65.9%),
      64.8% and 56.0% of the isolates were sensitive to amikacin, ciprofloxacin and
      gentamycin respectively.

PMID- 18092441
TI  - Pediatric inguinal hernia: controversies and decision making.
AB  - The pediatric inguinal hernia is the commonest defect the surgeon performs
      surgery on and is usually indirect. It is believed that these hernias rarely go
      away, and therefore, virtually all should be repaired. Much has been written
      about this condition, but the controversy on different aspects of it still
      exists. This article aims to address the controversies and decision making in
      pediatric inguinal hernias.

PMID- 18092442
TI  - Metabolic syndrome: are we at risk?
AB  - The metabolic syndrome also called syndrome X, is a constellation of interrelated
      risk factors of metabolic origin--metabolic risk factors--that appear to share
      insulin resistance as a possible pathogenetic factor that directly promote the
      development of atherosclerotic cardiovascular diseases and increase the risk for
      developing type 2 diabetes mellitus. The recommended first step for treatment of
      metabolic syndrome is lifestyle modifications such as weight loss, aerobic
      exercise, smoking cessation, and improved diet which independently improve
      insulin resistance and slow progression to type 2 diabetes mellitus. Even though
      success achieved through lifestyle modification is limited, the significance of
      it cannot be overemphasized. Specific dietary changes that are appropriate for
      addressing different aspects of the syndrome include reducing saturated fat
      intake to lower insulin resistance, reducing sodium intake to lower blood
      pressure, and reducing high-glycemic-index carbohydrate intake to lower
      triglyceride levels. Furthermore, drugs able to reduce insulin resistance, such
      as metformin and thiazolidinediones, already in the therapeutic armamentarium of
      type 2 diabetes, could be used in subjects with the metabolic syndrome as a
      preventive measure.

PMID- 18092443
TI  - The significance of plasma high density lipoprotein cholesterol (hdlc).
AB  - High Density Lipoprotein (HDL) transports in plasma, phospholipids, cholesterol,
      and triacylglycerol. The cholesterol associated with HDL (HDLc) is cholesterol
      that is scavenged from peripheral tissues back to liver. The liver converts this
      cholesterol into bile acids, bile salts, and esterifies the rest and secretes
      them into bile. Low HDLc is a risk factor for atherogenesis. Higher levels of
      HDLc in plasma are therefore an index of safety from coronary heart disease and
      atherosclerosis. Regular physical exercise, and changes in life style like
      cessation of smoking, lowered alcohol consumption, modified dietary fat intake
      and certain medications can improve the level of HDLc in plasma.

PMID- 18092444
TI  - Karyotype revealed 47, xxy chromosome (Klinefelter syndrome): a case report.
AB  - The Klinefelter syndrome is most common chromosomal cause of male infertility.
      However, the many cases of the syndrome remain undiagnosed due to variations in
      clinical presentation. A patient attended to surgical OPD with complaints of loss
      of secondary sexual characteristics and infertility. Physical examination
      revealed tall stature, thin built, small testes size, and absence of beard and
      pubic hairs. Karyotype and biochemical tests were performed to detect chromosomal
      abnormality as well hormonal level to confirm the diagnosis of androgen
      deficiency syndrome. Chromosomal complement confirmed the case of Klinefelter
      syndrome (47, XXY) causing androgen deficiency. Timely detection of Klinefelter
      syndrome is important to formulate further treatment modalities for the benefit
      of the patient.

PMID- 18092445
TI  - Progressive periodontal therapeutics for the general practice.

PMID- 18092446
TI  - Advantages of the root submergence technique for pontic site development in
      esthetic implant therapy.
AB  - A single-tooth implant in the esthetic region has good potential for success, but
      it is still challenging to restore multiple-tooth defects with implant-supported
      prostheses that resemble the natural dentition. This article suggests a strategy
      to provide a more predictable protocol for esthetic implant treatment for
      multiple-tooth defects using the root submergence technique (RST). By maintaining
      the natural tooth root with the RST a much greater amount of surrounding tissue
      may be preserved than with the commonly used socket preservation technique, which
      almost always leads to crestal bone resorption and thus reduction of the height
      of the interdental papillae and width of the edentulous ridge. RST instead
      maintains the natural attachment apparatus of the tooth in the pontic site, which
      in turn allows for complete preservation of the alveolar bone frame and assists
      in the creation of an esthetic result in adjacent multiple-tooth-replacement
      cases. In situations with periodontal bone loss, orthodontic extrusion is
      required to create the underlying bone support for the papilla that is necessary
      to guarantee predictability.

PMID- 18092447
TI  - Combined surgical and orthodontic approach to reproduce the physiologic eruption
      pattern in impacted canines: report of 25 patients.
AB  - The purpose of this study was to evaluate the periodontal variables of impacted
      maxillary canines that were treated with a combined surgical and orthodontic
      approach aimed at reproducing the physiologic eruption pattern of canines. Twenty
      five patients who presented with unilateral impacted maxillary canines were
      consecutively enrolled (age range, 13.2 to 23.2 years). They were treated with a
      surgical flap and orthodontic traction directed to the center of the crest and
      were evaluated periodontally at the end of treatment and again at a follow-up
      visit (2 to 5 years posttreatment). Pocket depth, keratinized tissue width, and
      gingival recession were recorded. At the end of orthodontic treatment, all 25
      treated canines presented with normal pocket depth (2.0 +/- 0.3 mm) and a normal
      amount of keratinized tissue (5.0 +/- 1.2 mm). No sites showed gingival
      recession. At the follow-up visit, both pocket depths and keratinized tissues
      were slightly reduced. The combined technique permits traction of the impacted
      canines to the center of the crest, simulating the physiologic eruption pattern
      and resulting in correct alignment and good periodontal status.

PMID- 18092448
TI  - Bone regenerated via rhPDGF-bB and a deproteinized bovine bone matrix:
      backscattered electron microscopic element analysis.
AB  - This study used backscattered electron microscopy (BSE-SEM) to analyze specimens
      in which bone was augmented both horizontally and vertically with a xenograft
      scaffold and recombinant human platelet-derived growth factor (rhPDGF-BB), with
      or without a resorbable collagen membrane. The study objective was to compare
      percentage weight and volume calcium-phosphorus ratios of regenerated bone and
      native bone and the nature of the bony contact with two different implant
      surfaces. Examination of the nature of the mineralized tissues by BSE-SEM
      provides an understanding of the composition and element ratio of bone
      regenerated from nonautogenous grafts. The data collected demonstrated no
      statistically significant difference between regenerated bone and native bone in
      the two tested groups. Our observations suggest that bone regenerated via
      nonautogenous grafts displays composition, structure, and physical properties
      very similar to those of native bone. Similarly, no significant differences were
      observed at the bone-implant interface between bone regenerated proximal to
      oxidized versus machined implants.

PMID- 18092449
TI  - Interpositional bone grafts in the posterior mandibular region: a report on six
      patients.
AB  - The purpose of this study was to evaluate treatment of resorbed posterior
      mandibles with interpositional bone grafts (the "sandwich" technique) and implant
      supported prostheses. Six consecutive patients with resorbed posterior mandibles
      (seven sites) were 4reated by the sandwich osteotomy technique with an
      interpositional bone graft harvested from the iliac crest. Vertical bone height
      was measured before surgery and 3 to 4 months later, prior to implant placement,
      on computed tomography scans to evaluate the augmentation obtained. In all the
      treated sites it was possible to place implants. None of the 21 implants placed
      failed, and minimal bone resorption was present 14 to 16 months after the
      prosthetic loading. If confirmed by long-term follow-up studies and more cases,
      these findings suggest that interpositional bone grafting in the posterior
      mandible could be a viable alternative to other surgical techniques.

PMID- 18092450
TI  - A 10-year multicenter retrospective clinical study of 1715 implants placed with
      the edentulous ridge expansion technique.
AB  - This work evaluates the data gathered over a period of 10 years on implants
      placed with the edentulous ridge expansion (ERE) technique by a group of
      specially trained and experienced surgeons. Between January 1992 and December
      2001, 1715 consecutive implants were placed with the ERE technique by nine
      different dental surgeons using a common surgical protocol. The implants were
      followed up using a common protocol and a specific database for the collection of
      clinical information on the patient, surgery, and follow-up, including the 1986
      Albrektsson et al criteria for implant success. All data gathered at the end of
      the study period were placed in a common database. The overall success rate over
      the O-year follow-up period was 95.7%.

PMID- 18092451
TI  - Fit of all-ceramic posterior fixed partial denture frameworks in vitro.
AB  - The objective of this study was to evaluate, by scanning electron microscopy, the
      marginal and internal fit of all-ceramic three-unit fixed partial denture (FPD)
      frames fabricated by computer-assisted design/computer-aided machining (CAD/CAM)
      and CAM techniques using blocks of infiltration ceramic, high-strength yttria
      stabilized tetragonal zirconia polycrystal (Y-TZP) zirconia sinter ceramic, high
      strength dense sintered Y-TZP zirconia ceramic, and glass ceramic. Slip-cast
      infiltration ceramic was used as a traditional control. The cementation interface
      widths of the FPD frame copings on butt (A) shoulders of Cerec In-Ceram zirconia
      (A1, 53 +/- 17 microm) were smaller than those of slip-cast In-Ceram zirconia
      (A6, 113 +/- 25 microm). Cerec Y-TZP zirconia (A2, 53 +/- 9 pm) and DCS Y-TZP
      zirconia (A4, 32 +/- 6 microm) interfaces were both significantly smaller than
      those of Cercon Y-TZP zirconia (A5, 120 +/- 6 microm). Internally, A2 (103 +/-
      14) interfaces were smaller than A4 interfaces (144 +/- 15 microm). On chamfer
      shoulders (B), Cerec Y-TZP zirconia (B1, 71 +/- 5 microm) interfaces were smaller
      than Cercon interfaces (B2, 129 +/- 38 microm); internally, B1 (80 +/- 11 microm)
      interfaces were smaller than B2 interfaces (130 +/- 12 microm). CAD/CAM produced
      better marginal and internal accuracy of fit compared to slip casting and CAM
      techniques.

PMID- 18092452
TI  - Histologic evaluation of an Nd:YAG laser-assisted new attachment procedure in
      humans.
AB  - This report presents histologic results in humans following a laser-assisted new
      attachment procedure (LANAP) for the treatment of periodontal pockets. Six pairs
      of single-rooted teeth with moderate to advanced chronic periodontitis associated
      with subgingival calculus deposits were treated. A bur notch was placed within
      the pocket at the clinically and radiographically measured apical extent of
      calculus. All teeth were scaled and root planed with ultrasonic and hand scalers.
      One of each pair of teeth received treatment of the inner pocket wall with a free
      running pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to remove the
      pocket epithelium, and the test pockets were lased a second time to seal the
      pocket. After 3 months, all treated teeth were removed en bloc for histologic
      processing. LANAP-treated teeth exhibited greater probing depth reductions and
      clinical probing attachment level gains than the control teeth. All LANAP-treated
      specimens showed new cementum and new connective tissue attachment in and
      occasionally coronal to the notch, whereas five of the six control teeth had a
      long junctional epithelium with no evidence of new attachment or regeneration.
      There was no evidence of any adverse histologic changes around the LANAP
      specimens. These cases support the concept that LANAP can be associated with
      cementum-mediated new connective tissue attachment and apparent periodontal
      regeneration of diseased root surfaces in humans.

PMID- 18092453
TI  - Accuracy of computerized tomography for the evaluation of mandibular sites prior
      to implant placement.
AB  - The objective of the present study was to observe the effect of positioning of
      the mandible on the accuracy of cross-sectional images obtained by reformatting
      computerized tomographic (CT) scans. An additional aim was to evaluate the
      ability of a software program (DentalVox, Era Scientific) to reconstruct these
      measurements on the reformatted images, regardless of the positioning of the
      mandible, accurately and without distortion. The test was carried out by
      examining a partially edentulous dry human mandible with an acrylic radiologic
      template. Through the use of an acrylic glass support, the mandible was
      positioned at angles of 0, 10, 15, 20, and 30 degrees relative to the scanning
      gantry, and a series of CT scans was performed that provided five sets of axial
      images. Each set of original axial images was reformatted by the DentalVox
      software, used first in its basic function, which is typical of all software for
      axial CT measurement (control group), and again in its function of site-specific
      multiplanar reconstruction (test group). The results showed that the position of
      the mandible in relation to the CT gantry can influence the precision of the
      linear measurements. The error ranged from 2% to 51%. The DentalVox software
      allowed the reconstruction of cross-sectional images with very little distortion
      regardless of the mandibular position.

PMID- 18092454
TI  - Effects of demineralized freeze-dried bone allograft on gene expression of
      osteoblastlike MG63 cells.
AB  - Demineralized freeze-dried bone allograft (DFDBA) is widely used in periodontal
      regeneration procedures as a scaffold for new bone formation in periodontal
      defects. How this biomaterial alters osteoblast activity to promote bone
      formation is poorly understood. We therefore attempted to address this question
      by using microarray techniques to identify genes that are differently regulated
      in osteoblasts exposed to DFDBA. By using DNA microarrays containing 20,000
      genes, the authors identified in an osteoblastlike cell line (MG-63) cultured
      with DFDBA (Allogro, Dentsply/Friadent-Ceramed) several genes whose expression
      was significantly up-regulated or down-regulated. The differently expressed genes
      cover a broad range of functional activities: (1) cell cycle regulation, (2)
      immunity, (3) vesicular transport, (4) production of cytoskeletal elements, and
      (5) bone remodeling. The data reported are, to the authors' knowledge, the first
      genetic portrait of DFDBA effects. They can be relevant to a better understanding
      of the molecular mechanism of bone regeneration and as a model for comparing
      other materials with similar clinical effects.

PMID- 18092455
TI  - Use of the natural tooth for soft tissue development: a case series.
AB  - The achievement of optimal esthetics around anterior dental implants has been a
      major challenge for many clinicians. The key to an esthetically pleasing
      appearance lies in the clinician's ability to properly manage the soft tissue
      profile around dental implants. Hence, the purpose of this case report is to
      describe a new technique that uses the patient's own natural tooth for the
      provisional implant restoration to develop soft tissue architecture that is
      almost identical to the patient's original immediately after tooth extraction.
      Ten consecutively treated patients were included in this series. Clinical
      measurements included soft tissue height, papilla appearance, and probing pocket
      depths. Other parameters such as radiographic bone levels and quality-of-life
      ratings were also recorded. Results from this study showed that all patients
      achieved a normal or Class 1 papilla appearance similar to the original
      appearance of the natural tooth. All patients were very happy with the treatment
      outcome. This newly suggested approach for restoring an anterior implant can be
      valuable and esthetically pleasing.

PMID- 18092456
TI  - Acinetobacter marinus sp. nov. and Acinetobacter seohaensis sp. nov., isolated
      from sea water of the Yellow Sea in Korea.
AB  - Two Gram-negative, nonmotile, coccobacilli, SW-3T and SW-100T, were isolated from
      sea water of the Yellow Sea in Korea. Strains SW-3T and SW-100T contained
      ubiquinone-9 (Q-9) as the predominant respiratory lipoquinone and C18:1 omega9c
      and C16:0 as the major fatty acids. The DNA G+C contents of strains SW-3T and SW
      100T were 44.1 mol% and 41.9 mol%, respectively. A neighbor-joining tree based on
      16S rRNA gene sequences showed that the two isolates fell within the evolutionary
      radiation enclosed by the genus Acinetobacter. Strains SW-3T and SW-100T
      exhibited a 16S rRNA gene similarity value of 95.7% and a mean DNA-DNA
      relatedness level of 9.2%. Strain SW-3T exhibited 16S rRNA gene sequence
      similarity levels of 93.5-96.9% to the validly described Acinetobacter species
      and fifteen Acinetobacter genomic species. Strain SW-100T exhibited 16S rRNA gene
      sequence similarity levels of less than 97.0% to the other Acinetobacter species
      except Acinetobacter towneri DSM 14962T (98.0% similarity). Strains SW-3T and SW
      100T exhibited mean levels of DNA-DNA relatedness of 7.3-16.7% to the type
      strains of some phylogenetically related Acinetobacter species. On the basis of
      phenotypic, phylogenetic, and genetic data, strains SW-3T and SW-100T were
      classified in the genus Acinetobacter as two distinct novel species, for which
      the names Acinetobacter marinus sp. nov. (type strain SW-3T=KCTC 12259T=DSM
      16312T) and Acinetobacter seohaensis sp. nov. (type strain SW-100T=KCTC
      12260T=DSM 16313T) are proposed, respectively.

PMID- 18092457
TI  - Heterologous expression and optimized one-step separation of levansucrase via
      elastin-like polypeptides tagging system.
AB  - Elastin-like polypeptides (ELPs) undergo a reversible inverse phase transition
      upon a change in temperature. This thermally triggered phase transition allows
      for a simple and rapid means of purifying a fusion protein. Recovery of ELPs
      tagged fusion protein was easily achieved by aggregation, triggered either by
      raising temperature or by adding salt. In this study, levansucrase has been used
      as a model enzyme in the development of a simple one-step purification method
      using ELPs. The levansucrase gene cloned from Pseudomonas aurantiaca S-4380 was
      tagged with various sizes of ELPs to functionally express and optimize the
      purification of levansucrase. One of two ELPs, ELP[V-20] or ELP[V-40], was fused
      at the C-terminus of the levansucrase gene. A levansucrase-ELP fusion protein was
      expressed in Escherichia coli DH5alpha at 37 degrees C for 18 h. The molecular
      masses of levansucrase-ELP[V-20] and levansucrase-ELP[V-40] were determined as 56
      kDa and 65 kDa, respectively. The phase transition of levansucrase-ELP[V-20]
      occurred at 20 degrees C in 50 mM Tris-Cl (pH 8) buffer with 3 M NaCl added,
      whereas the phase transition temperature (Tt) of levansucrase-ELP[V-40] was 17
      degrees C with 2 M NaCl. Levansucrase was successfully purified using the phase
      transition characteristics of ELPs, with a recovery yield of higher than 80%, as
      verified by SDS-PAGE. The specific activity was measured spectrophotometrically
      to be 173 U/mg and 171 U/mg for levansucrase-ELP[V-20] and levansucrase-ELP[V
      40], respectively, implying that the ELP-tagging system provides an efficient one
      step separation method for protein purification.

PMID- 18092458
TI  - Synbiotic synthesis of oligosaccharides during milk fermentation by addition of
      leuconostoc starter and sugars.
AB  - Synthesis of oligosaccharides during milk fermentation was attempted by
      inoculating Leuconostoc citreum with Lactobacillus casei, Lb. delbrueckii subsp.
      bulgaricus, and Streptococcus thermophilus as starters. Dextransucrase of Ln.
      citreum worked as a catalyst for the transglycosylation reaction of sugars;
      sucrose was added as the glucose donor, and lactose or maltose acted as the
      acceptor compound for the reaction. When 4% sucrose was added in milk, glucosyl
      lactose was synthesized (about 1%, w/v) after 1-2 days of fermentation at 15 or
      25 degrees C. Alternatively, when sucrose and maltose (2% each, w/v) were added,
      panose (about 1%, w/v) and other isomaltooligosaccharides were made in a day at
      15-35 degrees C. Growth patterns of lactobacilli and streptococci starters were
      not affected by the coculture of leuconostoc starter, but the rate of acid
      synthesis was slightly slowed at every temperature. Addition of sugars in milk
      did not give any adverse effect on the lactate fermentation. Accordingly, the use
      of leuconostoc starter and addition of sugars in milk allowed the production of
      oligosaccharides-containing fermented milk, and application of this method will
      facilitate the extensive development of synbiotic lactate foods.

PMID- 18092459
TI  - PCR-based specific detection of Ralstonia solanacearum by amplification of
      cytochrome c1 signal peptide sequences.
AB  - A polymerase chain reaction (PCR)-based method was developed to detect the DNA of
      Ralstonia solanacearum, the causal agent of bacterial wilt in various crop
      plants. One pair of primers (RALSF and RALSR), designed using cytochrome c1
      signal peptide sequences specific to R. solanacearum, produced a PCR product of
      932 bp from 13 isolates of R. solanacearum from several countries. The primer
      specificity was then tested using DNA from 21 isolates of Ralstonia, Pseudomonas,
      Burkholderia, Xanthomonas, and Fusarium oxysporum f. sp. dianthi. The specificity
      of the cytochrome c1 signal peptide sequences in R. solanacearum was further
      confirmed by a DNA-dot blot analysis. Moreover, the primer pair was able to
      detect the pathogen in artificially inoculated soil and tomato plants. Therefore,
      the present results indicate that the primer pair can be effectively used for the
      detection of R. solanacearum in soil and host plants.

PMID- 18092460
TI  - Change of sludge consortium in response to sequential adaptation to benzene,
      toluene, and o-xylene.
AB  - Activated sludge was sequentially adapted to benzene, toluene, and o-xylene (BTX)
      to study the effects on the change of microbial community. Sludge adapted to BTX
      separately degraded each by various rates in the following order; toluene>o
      xylene>benzene. Degradation rates were increased after exposure to repeated
      spikes of substrates. Eleven different kinds of sludge were prepared by the
      combination of BTX sequential adaptations. Clustering analyses (Jaccard, Dice,
      Pearson, and cosine product coefficient and dimensional analysis of MDS and PCA
      for DGGE patterns) revealed that acclimated sludge had different features from
      nonacclimated sludge and could be grouped together according to their prior
      treatment. Benzene- and xylene-adapted sludge communities showed similar
      profiles. The sludge profile was affected from the point of the final adaptation
      substrate regardless of the adaptation sequence followed. In the sludge adapted
      to 50 ppm toluene, Nitrosomonas sp. and bacterium were dominant, but these bands
      were not dominant in benzene and benzene after toluene adaptations. Instead,
      Flexibacter sp. was dominant in these cultures. Dechloromonas sp. was dominant in
      the culture adapted to 50 ppm benzene. Thauera sp. was the main band in the
      sludge adapted to 50 ppm xylene, but became vaguer as the xylene concentration
      was increased. Rather, Flexibacter sp. dominated in the sludge adapted to 100 ppm
      xylene, although not in the culture adapted to 250 ppm xylene. Two bacterial
      species dominated in the sludge adapted to 250 ppm xylene, and they also existed
      in the sludge adapted to 250 ppm xylene after toluene and benzene.

PMID- 18092461
TI  - Effect of multiple copies of cohesins on cellulase and hemicellulase activities
      of Clostridium cellulovorans mini-cellulosomes.
AB  - Cellulosomes in Clostridium cellulovorans are assembled by the interaction
      between the repeated cohesin domains of a scaffolding protein (CbpA) and the
      dockerin domain of enzyme components. In this study, we determined the
      synergistic effects on cellulosic and hemicellulosic substrates by three
      different recombinant mini-cellulosomes containing either endoglucanase EngB or
      endoxylanase XynA bound to mini-CbpA with one cohesin domain (mini-CbpA1), two
      cohesins (mini-CbpA12), or four cohesins (mini-CbpA1234). The assembly of EngB or
      XynA with mini-CbpA increased the activity against carboxymethyl cellulose, acid
      swollen cellulose, Avicel, xylan, and corn fiber 1.1-1.8-fold compared with that
      for the corresponding enzyme alone. A most distinct improvement was shown with
      corn fiber, a natural substrate containing xylan, arabinan, and cellulose.
      However, there was little difference in activity between the three different mini
      cellulosomes when the cellulosomal enzyme concentration was held constant
      regardless of the copy number of cohesins in the cellulosome. A synergistic
      effect was observed when the enzyme concentration was increased to be
      proportional to the number of cohesins in the mini-cellulosome. The highest
      degree of synergy was observed with mini-CbpA1234 (1.8-fold) and then mini-CbpA12
      (1.3-fold), and the lowest synergy was observed with mini-CbpA1 (1.2-fold) when
      Avicel was used as the substrate. As the copy number of cohesin was increased,
      there was more synergy. These results indicate that the clustering effect
      (physical enzyme proximity) of the enzyme within the mini-cellulosome is one of
      the important factors for efficient degradation of plant cell walls.

PMID- 18092462
TI  - Molecular orbital theory on cellulolytic reactivity between pNP
      cellooligosccharides and beta-glucosidase from Cellulomonas uda CS1-1.
AB  - A beta-glucosidase with the molecular mass of 160,000 Da was purified to
      homogeneity from cell extract of a cellulolytic bacterium, Cellulomonas uda CS1
      1. The kinetic parameters (Km and Vmax) of the enzyme were determined with pNP
      cellooligosccharides (DP 1-5) and cellobiose. The molecular orbital theoretical
      studies on the cellulolytic reactivity between the pNP-cellooligosaccharides as
      substrate (S) molecules and the purified beta-glucosidase (E) were conducted by
      applying the frontier molecular orbital (FMO) interaction theory. The results of
      the FMO interaction between E and S molecules verified that the first stage of
      the reaction was induced by exocyclic cleavage, which occurred in an
      electrophilic reaction based on a strong charge-controlled reaction between the
      highest occupied molecular orbital (HOMO) energy of the S molecule and the lowest
      occupied molecular orbital (LUMO) energy of the hydronium ion (H3O+), more than
      endocyclic cleavage, whereas a nucleophilic substitution reaction was induced by
      an orbital-controlled reaction between the LUMO energy of the oxonium ion (SH+)
      protonated to the S molecule and the HOMO energy of the H2O2 molecule. A
      hypothetic reaction route was proposed with the experimental results in which the
      enzymatic acid-catalyst hydrolysis reaction of E and S molecules would be
      progressed via SN1 and SN2 reactions. In addition, the quantitative structure
      activity relationships (QSARs) between these kinetic parameters showed that Km
      has a significant correlation with hydrophobicity (logP), and specific activity
      has with dipole moment, respectively.

PMID- 18092463
TI  - Damage to the cytoplasmic membrane and cell death caused by lycopene in Candida
      albicans.
AB  - Lycopene, an acyclic carotenoid found in tomatoes (Lycopersicon esculentum) and a
      number of fruits, has shown various biological properties, but its antifungal
      effects remain poorly understood. The current study investigated the antifungal
      activity of lycopene and its mode of action. Lycopene showed potent antifungal
      effects toward pathogenic fungi, tested in an energy-independent manner, with low
      hemolytic effects against human erythrocytes. To confirm the antifungal effects
      of lycopene, its effects on the dimorphism of Candida albicans induced by fetal
      bovine serum (FBS), which plays a key role in the pathogenesis of a host
      invasion, were investigated. The results showed that lycopene exerted potent
      antifungal activity on the serum-induced mycelia of C. albicans. To understand
      the antifungal mode of action of lycopene, the action of lycopene against fungal
      cell membranes was examined by FACScan analysis and glucose and trehalose-release
      test. The results indicated that lycopene caused significant membrane damage and
      inhibited the normal budding process, resulting from the destruction of membrane
      integrity. The present study indicates that lycopene has considerable antifungal
      activity, deserving further investigation for clinical applications.

PMID- 18092464
TI  - Effects of application of Rhodopseudomonas sp. on seed germination and growth of
      tomato under axenic conditions.
AB  - Purple nonsulfur bacteria were isolated from river sediments and their growth
      promoting capabilities on tomato were examined. Isolated strains KL9 and BL6 were
      identified as Rhodopseudomonas spp. by 16S rDNA sequence analysis.
      Rhodopseudomonas strain KL9 maximally produced 5.56 mM/ min/mg protein and 67.2
      microM/min/mg protein of indole-3-acetic acid (IAA) and 5-aminolevulinic acid
      (ALA), respectively, which may be one of the mechanisms of plant growth
      enhancement. The germination percentage of tomato seed, total length, and dry
      mass of germinated tomato seedling increased by 30.2%, 71.1%, and 270.8%,
      respectively, compared with those of the uninoculated control 7 days after
      inoculation of strain KL9. The lengths of the root and shoot of germinated
      seedling treated with 3 mM tryptophan, a precursor of IAA, increased by 104.4%
      and 156.5%, respectively, 7 days after inoculation of strain KL9.
      Rhodopseudomonas KL9 increased 123.5% and 54% of the root and shoot lengths of
      germinated seedling, respectively, treated with 15 mM glycine and succinate,
      precursors of ALA. This plant growth promoting capability of purple nonsulfur
      bacteria may be a candidate for a biofertilizer in agriculture.

PMID- 18092465
TI  - Characterization of xylanase from Lentinus edodes M290 cultured on waste mushroom
      logs.
AB  - Extracellular enzymes from Lentinus edodes M290 on normal woods (Quercus
      mongolica) and waste logs from oak mushroom production were comparatively
      investigated. Endoglucanase, cellobiohydrolase, beta-glucosidase, and xylanase
      activities were higher on waste mushroom logs than on normal woods after L.
      edodes M290 inoculation. Xylanase activity was especially different, with a three
      times higher activity on waste mushroom logs. When the waste mushroom logs were
      used as a carbon source, a new 35 kDa protein appeared. After the purification,
      the optimal pH and temperature for xylanase activity were determined to be 4.0
      and 50 degrees C, respectively. More than 50% of the optimal xylanase activity
      was retained when the temperature was increased from 20 to 60 degrees C, after a
      240 min reaction. At 40 degrees C, the xylanase maintained 93% of the optimal
      activity, after a 240 min reaction. The purified xylanase showed a very high
      homology to the xylanase family 10 from Aspergillus terreus by LC/MS-MS analysis.
      The highest Xcorr (1.737) was obtained from the peptide KWI SQGIPIDGIG SQTHLGSGGS
      WTVK originated from Aspergillus terreus, indicating that the 35 kDa protein was
      xylanase. This protein showed low homology to a previously reported L. edodes
      xylanase sequence.

PMID- 18092466
TI  - Genetic characterization of two S-adenosylmethionine-induced ABC transporters
      reveals their roles in modulations of secondary metabolism and sporulation in
      Streptomyces coelicolor M145.
AB  - S-Adenosylmethionine (SAM) was previously documented to activate secondary
      metabolism in a variety of Streptomyces spp. and to promote actinorhodin (ACT)
      and undecylprodigiosin (RED) in Streptomyces coelicolor. The SAM-induced proteins
      in S. coelicolor include several ABC transporter components (SCO5260 and SCO5477)
      including BldKB, the component of a well-known regulatory factor for
      differentiations. In order to assess the role of these ABC transporter complexes
      in differentiation of Streptomyces, SCO5260 and SCO5476, the first genes from the
      cognate complex clusters, were individually inactivated by gene replacement.
      Inactivation of either SCO5260 or SCO5476 led to impaired sporulation on agar
      medium, with the more drastic defect in the SCO5260 null mutant (ASCO5260).
      ASCO5260 displayed growth retardation and reduced yields of ACT and RED in liquid
      cultures. In addition, SAM supplementation failed in promoting the production of
      ACT and RED in ASCO5260. Inactivation of SCO5476 gave no significant change in
      growth and production of ACT and RED, but impaired the promoting effect of SAM on
      ACT production without interfering with the effect on RED production. The present
      study suggests that SAM induces several ABC transporters to modulate secondary
      metabolism and morphological development in S. coelicolor.

PMID- 18092467
TI  - Photolithographic fabrication of poly(ethylene glycol) microstructures for
      hydrogel-based microreactors and spatially addressed microarrays.
AB  - We describe the fabrication of poly(ethylene glycol) diacrylate (PEG-DA) hydrogel
      microstructures with a high aspect ratio and the use of hydrogel microstructures
      containing the enzyme beta-galactosidase (beta-Gal) or glucose oxidase
      (GOx)/horseradish peroxidase (HRP) as biosensing components for the simultaneous
      detection of multiple analytes. The diameters of the hydrogel microstructures
      were almost the same at the top and at the bottom, indicating that no
      differential curing occurred through the thickness of the hydrogel
      microstructure. Using the hydrogel microstructures as microreactors, beta-Gal or
      GOx/HRP was trapped in the hydrogel array, and the time-dependent fluorescence
      intensities of the hydrogel array were investigated to determine the dynamic
      uptake of substrates into the PEG-DA hydrogel. The time required to reach steady
      state fluorescence by glucose diffusing into the hydrogel and its enzymatic
      reactions with GOx and HRP was half the time required for resorufin beta-D
      galactopyranoside (RGB) when used as the substrate for beta-Gal. Spatially
      addressed hydrogel microarrays containing different enzymes were micropatterned
      for the simultaneous detection of multiple analytes, and glucose and RGB
      solutions were incubated as substrates. These results indicate that there was no
      cross-talk between the beta-Gal-immobilizing hydrogel micropatches and the
      GOx/HRP-immobilizing micropatches.

PMID- 18092468
TI  - Allexivirus transmitted by eriophyid mites in garlic plants.
AB  - Viruses in garlic plants (Allium sativum L.) have accumulated and evolved over
      generations, resulting in serious consequences for the garlic trade around the
      world. These viral epidemics are also known to be caused by aphids and eriophyid
      mites (Aceria tulipae) carrying Potyviruses, Carlaviruses, and Allexiviruses.
      However, little is known about viral epidemics in garlic plants caused by
      eriophyid mites. Therefore, this study investigated the infection of garlic
      plants with Allexiviruses by eriophyid mites. When healthy garlic plants were
      cocultured with eriophyid mites, the leaves of the garlic plants developed yellow
      mosaic strips and became distorted. In extracts from the eriophyid mites,
      Allexiviruses were observed using immunosorbent electron microscopy (ISEM). From
      an immunoblot analysis, coat proteins against an Allexivirus garlic-virus
      antiserum were clearly identified in purified extracts from collected viral
      infected garlic plants, eriophyid mites, and garlic plants infected by eriophyid
      mites. A new strain of GarV-B was isolated and named GarV-B Korea isolate 1 (GarV
      B1). The ORF1 and ORF2 in GarV-B1 contained a typical viral helicase, RNA
      directed RNA polymerase (RdRp), and triple gene block protein (TGBp) for viral
      movement between cells. The newly identified GarV-B1 was phylogenetically grouped
      with GarV-C and GarV-X in the Allexivirus genus. All the results in this study
      demonstrated that eriophyid mites are a transmitter insect species for
      Allexiviruses.

PMID- 18092469
TI  - Molecular interactions of a replication initiator protein, RepA, with the
      replication origin of the enterococcal plasmid p703/5.
AB  - We previously identified the origin of replication of p703/5, a small cryptic
      plasmid from the KBL703 strain of Enterococcus faecalis. The origin of
      replication contains putative regulatory cis-elements required for replication
      and a replication initiator (RepA) gene. The replicon of p703/5 is similar in its
      structural organization to theta-type plasmids, and RepA is homologous to a
      family of Rep proteins identified in several plasmids from Gram-positive
      bacteria. Here, we report molecular interactions between RepA and the replication
      origin of p703/5. DNase I footprinting using recombinant RepA together with
      electrophoretic mobility shift assays confirmed the binding of RepA to the
      replication origin of p703/5 via iterons and an inverted repeat. We also
      demonstrated the formation of RepA dimers and the different binding of RepA to
      the iteron and the inverted repeat using gel filtration chromatographic analysis,
      a chemical crosslinking assay, and electrophoretic mobility shift assays in the
      presence of guanidine hydrochloride. Our results suggest that RepA plays a
      regulatory role in the replication of the enterococcal plasmid p703/5 via
      mechanisms similar to those of typical iteron-carrying theta-type plasmids.

PMID- 18092470
TI  - Antibacterial activity of essential oils on the growth of Staphylococcus aureus
      and measurement of their binding interaction using optical biosensor.
AB  - Antibacterial activity of essential oils (Tea tree, Chamomile, Eucalyptus) on
      Staphylococcus aureus growth was evaluated as well as the essential oil-loaded
      alginate beads. The binding interactions between the cell and the essential oils
      were measured using an optical biosensor. The antibacterial activity of the
      essential oils to the cell was evaluated with their binding interaction and
      affinity. The antibacterial activity appeared in the order of Tea Tree>
      Chamomile>Eucalyptus, in comparison of the inhibition effects of the cell growth
      to the essential oils. The association rate constant and affinity of the cell
      binding on Tea Tree essential oil were 5.0 x 10(-13) ml/(CFU-s) and 5.0 x 10(5)
      ml/CFU, respectively. The affinity of the cell binding on Tea Tree was about
      twice higher than those on the other essential oils. It might be possible that an
      effective antibacterial activity of Tea Tree essential oil was derived from its
      strong adhesive ability to the cell, more so than those of the other essential
      oils.

PMID- 18092471
TI  - Mithramycin inhibits etoposide resistance in glucose-deprived HT-29 human colon
      carcinoma cells.
AB  - Physiological cell conditions such as glucose deprivation and hypoxia play roles
      in the development of drug resistance in solid tumors. These tumor-specific
      conditions cause decreased expression of DNA topoisomerase IIalpha, rendering
      cells resistant to topo II target drugs such as etoposide. Thus, targeting tumor
      specific conditions such as a low glucose environment may be a novel strategy in
      the development of anticancer drugs. On this basis, we established a novel
      screening program for anticancer agents with preferential cytotoxic activity in
      cancer cells under glucose-deprived conditions. We recently isolated an active
      compound, AA-98, from Streptomyces sp. AA030098 that can prevent stress-induced
      etoposide resistance in vitro. Furthermore, LC-MS and various NMR spectroscopic
      methods identified AA-98 as mithramycin, which belongs to the aureolic acid group
      of antitumor compounds. We found that mithramycin prevents the etoposide
      resistance that is induced by glucose deprivation. The etoposide-chemosensitive
      action of mithramycin was just dependent on strict low glucose conditions, and
      resulted in the selective cell death of etoposide-resistant HT-29 human colon
      cancer cells.

PMID- 18092473
TI  - Optimization of expression conditions for soluble protein by using a robotic
      system of multi-culture vessels.
AB  - We have developed a robotic system for an automated parallel cell cultivation
      process that enables screening of induction parameters for the soluble expression
      of recombinant protein. The system is designed for parallelized and simultaneous
      cultivation of up to 24 different types of cells or a single type of cell at 24
      different conditions. Twenty-four culture vessels of about 200 ml are arranged in
      four columns x six rows. The system is equipped with four independent
      thermostated waterbaths, each of which accommodates six culture vessels. A two
      channel liquid handler is attached in order to distribute medium from the
      reservoir to the culture vessels, to transfer seed or other reagents, and to take
      an aliquot from the growing cells. Cells in each vessel are agitated and aerated
      by sparging filtered air. We tested the system by growing Escherichia coli
      BL21(DE3) cells harboring a plasmid for a model protein, and used it in
      optimizing protein expression conditions by varying the induction temperature and
      the inducer concentration. The results revealed the usefulness of our custom-made
      cell cultivation robot in screening optimal conditions for the expression of
      soluble proteins.

PMID- 18092472
TI  - Individual LPS responsiveness depends on the variation of toll-like receptor
      (TLR) expression level.
AB  - An individual's immune response is critical for host protection from many
      different pathogens, and the responsiveness can be assessed by the amount of
      cytokine production upon stimulating bacterial components such as
      lipopolysaccharide (LPS). The difference between individuals in their peripheral
      blood mononuclear cells (PBMC) responsiveness to LPS, a Gram-negative endotoxin,
      was investigated from 27 healthy individuals. We observed a large variation in
      IFNgamma production among different individuals. The PBMC of the consistently
      three highest and three lowest IFNgamma producers were investigated. Since
      previous studies described that a single point mutation in the coding region of
      TLR2 and TLR4 is linked to the individual responsiveness to pathogenic bacterial
      infections, we first examined the known point mutations in the coding region of
      TLR2Pro681His, TLR4Pro714His located in the cytoplasmic regions of the Toll-like
      domain as well as TLR4Asp299Gly located in the extracellular region. None of
      these mutations were associated with an individual's responsiveness to LPS,
      despite the presence of TLR4Asp299Gly mutation. Further investigation revealed
      that the variation of PBMC responsiveness to LPS among healthy individuals was
      due to constitutive expression levels of TLR4 and TLR2. This result is consistent
      with an aging-related low expression of Toll-like receptors in the mouse model of
      LPS responsiveness. The present study therefore suggests that the constitutive
      expression levels of TLR2 and TLR4 may contribute to the individual response to
      LPS.

PMID- 18092474
TI  - Arthrobacter subterraneus sp. nov., isolated from deep subsurface water of the
      South Coast of Korea.
AB  - Strain CH7T, a pale yellow-pigmented bacterium and new isolate from deep
      subsurface water of the South Coast of Korea, was subjected to a polyphasic
      taxonomic study. CH7T grew between 5 and 37 degrees C, pH 5.3-10.5, and tolerated
      up to 13% NaCl. A phylogenetic analysis based on 16S rRNA gene sequences showed
      that strain CH7T was associated with the genus Arthrobacter and phylogenetically
      closely related to the type strains Arthrobacter tumbae (99.4%) and Arthrobacter
      parietis (99.1%). However, DNA-DNA hybridization experiments revealed 2.1% and
      12% between strain CH7T and Arthrobacter tumbae and Arthrobacter parietis,
      respectively. Thus, the phenotypic and phylogenetic differences suggested that
      CH7T should be placed in the genus Arthrobacter as a novel species, for which the
      name Arthrobacter subterraneus sp. nov. is proposed. In addition, the type strain
      for the new species is CH7T (=KCTC 9997T=DSM 17585T).

PMID- 18092475
TI  - Optimization of antibacterial activity by Gold-Thread (Coptidis Rhizoma Franch)
      against Streptococcus mutans using evolutionary operation-factorial design
      technique.
AB  - This study was conducted to find the optimum extraction condition of Gold-Thread
      for antibacterial activity against Streptococcus mutans using The evolutionary
      operation-factorial design technique. Higher antibacterial activity was achieved
      in a higher extraction temperature (R2 = -0.79) and in a longer extraction time
      (R2 = -0.71). Antibacterial activity was not affected by differentiation of the
      ethanol concentration in the extraction solvent (R2 = -0.12). The maximum
      antibacterial activity of clove against S. mutans determined by the EVOP
      factorial technique was obtained at 80 degrees C extraction temperature, 26 h
      extraction time, and 50% ethanol concentration. The population of S. mutans
      decreased from 6.110 logCFU/ml in the initial set to 4.125 logCFU/ml in the third
      set.

PMID- 18092476
TI  - Improvement of antigen blotting in a tissue blot immunobinding assay for the
      detection of two chili pepper viruses.
AB  - The tissue blot immunobinding assay (TBIA) is widely used for the detection and
      localization of plant viruses in various plant tissues. The basic experimental
      procedures of TBIA sampling and blotting were simplified using commercially
      available micropipette tips. This method was termed the ring-blot immunobinding
      assay (R-BIA), as the blot on the membrane forms a ring shape. The detection
      efficacy of R-BIA was tested for two chili pepper viruses, pepper mild mottle
      tobamovirus (PMMoV) and pepper mottle potyvirus (PepMoV), following the optimized
      serological procedures of TBIA (length of the incubation period and BSA
      concentration, and primary and secondary antibodies). Sensitivity of the R-BIA
      was about 1 ng/ml of purified PMMoV in pepper leaf sap from a healthy pepper
      plant. R-BIA also showed high specificity in the detection of PMMoV and PepMoV.
      Moreover, the modified sampling and blotting procedures were simpler and more
      reliable than other TBIA methods (such as whole-leaf blotting and crushed-leaf
      blotting), suggesting that the R-BIA may be used for medium- to large-scale
      detection of plant viruses in laboratories with minimal facilities.

PMID- 18092477
TI  - Cloning and expression of a parathion hydrolase gene from a soil bacterium,
      Burkholderia sp. JBA3.
AB  - A bacterium, Burkholderia sp. JBA3, which can mineralize the pesticide parathion,
      was isolated from an agricultural soil. The strain JBA3 hydrolyzed parathion to p
      nitrophenol, which was further utilized as the carbon and energy sources. The
      parathion hydrolase was encoded by a gene on a plasmid that strain JBA3 harbored,
      and it was cloned into pUC19 as a 3.7-kbp Sau3AI fragment. The ORF2 (ophB) in the
      cloned fragment encoded the parathion hydrolase composed of 526 amino acids,
      which was expressed in E. coli DH10B. The ophB gene showed no significant
      sequence similarity to most of other reported parathion hydrolase genes.

PMID- 18092478
TI  - Changes in aurantio-obtusin and glucoaurantio-obtusin content in Cassiae Semen
      via treatment with a crude enzyme extract from Aspergillus usamii.
AB  - Cassiae Semen (seeds of Cassia tora) showed a remarkably different HPLC
      chromatogram after being treated with a crude enzyme extract from Aspergillus
      usamii. Increased and decreased compounds were identified as aurantio-obtusin and
      glucoaurantio-obtusin, respectively. The aurantio-obtusin content reached its
      maximum level (133.58 +/- 0.39 microg/mg extract) after being incubated for 50
      min at 37 degrees C, whereas the inactivated crude enzyme-treated control
      remained unchanged (54.13 +/- 1.33 microg/mg). On the other hand, the
      glucoaurantio-obtusin content decreased by less than one-third (51.09 +/- 1.63
      microg/ mg) of the untreated control (143.19 +/- 2.12 microg/mg), suggesting that
      an increase in aurantio-obtusin content originated from the enzymatic cleavage of
      its glucoside glucoaurantio-obtusin.

PMID- 18092479
TI  - Modulation of the tendency towards inclusion body formation of recombinant
      protein by the addition of glucose in the araBAD promoter system of Escherichia
      coli.
AB  - We attempted to modulate the overall protein expression rate through the addition
      of a repressor against the araBAD promoter system of Escherichia coli, in which
      glucose was used as a repressor. Therefore, 0.5% L-arabinose was initially
      contained as an inducer in culture medium, and either 2% glucose or 2% glycerol
      was used as a carbon source, and it was found that the expression of recombinant
      interferon-alpha could be observed at the beginning of the batch culture when
      glycerol was used as a carbon source. However, when glucose was used, the
      initiation of recombinant interferon-alpha expression was delayed compared with
      that when glycerol was used. Furthermore, when the addition of 0.5% glucose was
      carried out once or twice after 0.5% L-arabinose induction during DO-stat fed
      batch culture, the distributions of soluble and insoluble recombinant interferon
      alpha were modulated. When glucose was not added after the induction of L
      arabinose, all of the expressed recombinant interferon-alpha formed an inclusion
      body during the later half of culturing. However, when glucose was added after
      induction, the expressed recombinant interferon-alpha, did not all form an
      inclusion body, and about half of the total recombinant interferon-alpha was
      expressed in a soluble form. It was deduced that the addition of glucose after
      the induction of L-arabinose might lower the cAMP level, and thus, CAP
      (catabolite activator protein) might not be activated. The transcription rate of
      recombinant interferon-alpha in the araBAD promoter system might be delayed by
      the partial repression. This inhibition of the transcription rate probably
      resulted in more soluble interferon-alpha expression caused by the reduction of
      the protein synthesis rate.

PMID- 18092480
TI  - New fermentation technique for complete digestion of soybean protein.
AB  - The aim of this study was to develop a new fermentation method in order to
      improve the digestion of soybean protein, and to promote normal fermentation of
      soybean. A proximate composition, such as moisture, pH, and reducing sugar, of
      fermented soybeans by the new fermentation was similar to those of controls.
      Neutral protease activity, the most important factor for fermented soybean
      products, was the highest, having about 636 U/g at 54 h fermentation. The content
      of total free amino acid was almost 3-18 times higher than controls. The three
      step fermented soybeans can be used as a functional food ingredient for human
      consumption, with higher protein digestibility.

PMID- 18092481
TI  - The serendipitous gift of epiphany.

PMID- 18092482
TI  - Brown's involvement in the health of less developed countries.

PMID- 18092483
TI  - Brown's Fogarty International Center AIDS International Research and Training
      Program: building capacity and new collaborations.

PMID- 18092484
TI  - The dual burden of infectious and non-communicable diseases in the Asia-Pacific
      region: examples from the Philippines and the Samoan Islands.

PMID- 18092485
TI  - Perspectives from Brown medical students and a medical resident. The Warren
      Alpert medical school in the Dominican Republic.

PMID- 18092486
TI  - Going home: lessons for a Brown medical student in Cambodia.

PMID- 18092487
TI  - "Village health works" in Burundi.

PMID- 18092488
TI  - Caring for HIV-infected refugees in Rhode Island.

PMID- 18092489
TI  - Tuberculosis peritonitis.

PMID- 18092490
TI  - HEALTHpact plans for small employer: physician's role.

PMID- 18092491
TI  - Refugee health update: lead exposure in refugee children.

PMID- 18092493
TI  - Communication.

PMID- 18092492
TI  - Recent requirements under the author byline disclosing any financial interests.

PMID- 18092494
TI  - Failure to recognize and treat.

PMID- 18092495
TI  - Breaking down barriers. Language is the issue.

PMID- 18092496
TI  - Health care worker influenza vaccination reduces risk to patients: hospital
      immunizations reduce nosocomial outbreaks.

PMID- 18092497
TI  - 'CALL' system allows quicker heart attack treatment.

PMID- 18092498
TI  - Legally speaking: strategies for defending payor audits.

PMID- 18092499
TI  - An unusual case of shingles.

PMID- 18092500
TI  - Ripple effect: ethics begin with the board.
AB  - Understanding and upholding the highest ethical standards has never had higher
      stakes for boards, but it often means choosing between several "rights."

PMID- 18092501
TI  - Quality exponential: the journey from 100,000 to 5 million lives.
AB  - The tremendous success of the Institute for Healthcare Improvement's 100,000
      Lives Campaign has inspired an even more ambitious sequel. Can hospitals save 5
      million lives over the next two years?

PMID- 18092502
TI  - Trustee workbook 4. Asset stewardship and the board.

PMID- 18092503
TI  - States on stage. Trying out new coverage initiatives.
AB  - Several states are trying out their own health care coverage initiatives, finding
      both encouraging success and new, daunting challenges.

PMID- 18092504
TI  - Bonding with physicians: hospitals and IT donations.

PMID- 18092505
TI  - The case for continuous compliance.

PMID- 18092506
TI  - Fund raising: innovative fund raising brings art to a hospital.

PMID- 18092507
TI  - Effects of worn-out soles on lower limb stability, shock absorption and energy
      cost during prolonged walking.
AB  - This study investigated the effects of worn-out shoes on lower leg stability,
      shock absorption and energy cost during prolonged walking. Seven male subjects
      (23.4 +/- 0.5 yr) walked at 4.8 km/h for 60 minutes wearing three different pairs
      of shoes: two of these pairs had severely and moderately worn soles (EASC:
      Excessive Attrite Shoe Condition and MASC: Moderate Attrite Shoe Condition,
      respectively) and the other pair had no wear (NASC: No Attrite Shoe Condition).
      Impact acceleration at the subtalar at heel strike, rearfoot angles (the subtalar
      joint and the lower leg) during stance phase, and oxygen uptake (VO2) were
      measured throughout the 60-minute walk. At the 10th minute of walking, worn-out
      shoes increased the supination of the subtalar joint and extortion of the lower
      leg. In addition, VO2 was significant larger in EASC (808.3 ml x min(-1)) than in
      NASC (749.5 ml x min(-1)). During the 60-minute walk, however, there were no time
      effects of shoe condition on the rearfoot angles and on VO2. In contrast, impact
      acceleration at the subtalar joint in EASC remained almost constant until the
      30th minute of walking, and then began to elevate. In conclusion, worn-out shoes
      increased the energy cost and reduced lower leg stability during walking,
      although these changes were not influenced by walking duration within 60 minutes.
      However, prolonged walking showed the potential negative effect of worn-out shoe
      on shock absorption.

PMID- 18092508
TI  - Difference in abdominal muscularity at the umbilicus level between young and
      middle-aged men.
AB  - This study aimed to examine how the muscularity of the abdomen at the umbilicus
      level differs between sedentary middle-aged and young men. Magnetic resonance
      imaging was applied to determine the cross-sectional areas of skeletal muscle,
      subcutaneous fat, and interperitoneal tissue in 43 middle-aged (40 58yrs) and 38
      young (21-29 yrs) men. The cross-sectional area of the skeletal muscle was
      analyzed as the sum of those of the rectus abdominis, abdominal oblique, lower
      back, and iliopsoas skeletal muscle groups. The middle-aged men showed greater
      waist circumference and whole abdominal cross-sectional area than the young men.
      In addition, the cross-sectional areas of subcutaneous fat and interperitoneal
      tissue were greater in the middle-aged men than in the young men. However, the
      total cross-sectional area of the skeletal muscle was similar between the two
      groups, although its percentage to the whole abdominal cross-sectional area was
      higher in the young men compared to the middle-aged men. Among the four skeletal
      muscle groups analyzed, the percentage of the cross-sectional areas in abdominal
      oblique muscles to that of total skeletal muscle was higher in the middle-aged
      men than in the young men and that of the lower back muscles was the reverse.
      These results were similar even when cross-sectional area data were analyzed
      using a subsample (33 middle-aged and 23 young men) matched for body height and
      mass. Thus, the present study indicated that the total muscularity of the abdomen
      at the umbilicus level was similar between the middle-aged and young men, but the
      relative distributions of lower back and abdominal oblique muscles varied between
      the two generations.

PMID- 18092509
TI  - Segmental body composition assessment for obese Japanese adults by single
      frequency bioelectrical impedance analysis with 8-point contact electrodes.
AB  - This study aimed to determine the accuracy of segmental body composition
      variables estimated by single-frequency BIA with 8-point contact electrodes (SF
      BIA8), compared with dual-energy X-ray absorptiometry (DXA). Subjects were 72
      obese Japanese adults (43 males and 29 females) aged 30 to 66 years. Segmental
      body composition variables (fat free mass: FFM, fat mass: FM, and percent fat
      mass: %FAT) were measured by these techniques. The correlations between impedance
      values and FFM measured by DXA were calculated. To examine the consistency in
      predicted values (SF-BIA8) with the reference (DXA), significant mean differences
      were tested by t-test and the degree of the difference was assessed by effect
      size. Correlations between the reference and predicted values were calculated.
      Additionally, the standard error of estimation (SEE) when estimating the
      reference from the predictor and the relative value of the SEE to the mean value
      of the DXA measurement (%SEE) were calculated. Systematic error was examined by
      Bland-Altman plots. High correlations were found between impedance and FFM
      measured by SF-BIA8. FFM in the extremities showed high correlations with the
      reference values, but systematic error was found. SF-BIA8 tended to overestimate
      FFM in the trunk. The consistencies in %FAT and FM with the reference value are
      inferior to those for FFM, and SEE values in %FAT and FM were greater than those
      for FFM. The accuracy of the estimated values in the trunk (FFM, %FAT, and FM)
      are inferior to those of the total body and extremities.

PMID- 18092510
TI  - Electromyographic data do not support a progressive recruitment of muscle fibers
      during exercise exhibiting a VO2 slow component.
AB  - The origin of the slow component (SC) of oxygen uptake kinetics, presenting
      during exercise above the ventilatory threshold (VT), remains unclear. Possible
      physiologic mechanisms include a progressive recruitment of type II muscle
      fibers. The purpose of this study was to examine alterations in muscle activity
      through electromyography (EMG) and mean power frequency (MPF) analysis during
      heavy cycling exercise. Eight trained cyclists (mean +/- S.E.; age = 30 +/- 3
      years, height = 1771 +/- 4 cm, weight = 73.8 +/- 6.5 kg, VO2max = 4.33 +/- 0.28 l
      min(-1)) completed transitions from 20W to a workload equaling 50% of the
      difference between V(T) and VO2max. VO2 was monitored using a breath-by-breath
      measurement system, and EMG data were gathered from surface electrodes placed on
      the gastrocnemius lateralis and vastus lateralis oblique. Breath-by-breath data
      were time aligned, averaged, interpolated to 1-s intervals, and modeled with non
      linear regression. Mean power frequency (MPF) and RMS EMG values were calculated
      for each minute during the exercise bout. Additionally, MPF was determined using
      both isolated EMG bursts and complete pedal revolutions. All subjects exhibited a
      VO2 SC (mean amplitude = 0.98 +/- 0.16 l min(-1)), yet no significant differences
      were observed during the exercise bout in MPF or RMS EMG data (p > 0.05) using
      either analysis technique. While it is possible that the sensitivity of EMG may
      be insufficient to identify changes in muscle activity theorized to affect the
      VO2 SC, the data indicated no relationship between MPF/EMG and the SC during
      heavy cycling.

PMID- 18092511
TI  - BCG immunization age in urban and rural areas of Akita Prefecture, Japan.
AB  - BCG immunization, utilizing whole-body coordination, is a highly cost-effective
      means of health intervention for preventing miliary tuberculosis (TB) and TB
      meningitis. In this study, we investigated the appropriate age by which a child
      should have completed his or her BCG immunization and discuss the current BCG
      immunization rate in Akita Prefecture, Japan. BCG immunization rates in urban and
      rural areas were 90.1% and 80.7%, respectively. Our immunization data were lower
      than the World Health Organization's (WHO) recommended rate. Immunization
      coverage rates in urban settings were higher than those in rural areas among
      infants four months to fifteen months of age, except for those six months old. We
      recommend: (1) completing BCG immunization by the age of twelve months, (2)
      preparing and educating parents for BCG immunization by means of a health policy,
      and (3) changing BCG immunization methods from group to individual inoculation.
      Immunization coverage rates may be increased or maintained to prevent miliary TB
      and TB meningitis.

PMID- 18092512
TI  - Preliminary study of a physiological evaluation method on attentiveness
      concentration during mental arithmetic; correlation between task performance and
      physiological indices.
AB  - It is important that task performance is physiologically evaluated in
      consideration of arousal level. But there are relatively few preceding studies.
      In this study, the relationship between task performance and physiological
      indices was studied with regard to attentiveness concentration. The subjects were
      eight healthy college students. They performed calculations and a visual display
      terminal (VDT) task. Electroencephalogram (EEG) frequency component, alpha
      attenuation coefficient (AAC), skin potential level (SPL), blood flow of the
      finger tip skin (BF), and visual analog scale (VAS), were measured. In order to
      quantify task performance, correlations between the task performance and
      physiological indices during the mental task were analyzed. The results suggest
      that AAC correlates with the error rate in calculation. BF also correlates with
      the error rate in calculation, while the calculation speed correlates with SPL.
      It can be inferred that the task speed and error rate are supposed to be related
      to the different physiological background.

PMID- 18092513
TI  - Microultrasound molecular imaging of vascular endothelial growth factor receptor
      2 in a mouse model of tumor angiogenesis.
AB  - High-frequency microultrasound imaging of tumor progression in mice enables
      noninvasive anatomic and functional imaging at excellent spatial and temporal
      resolution, although microultrasonography alone does not offer molecular scale
      data. In the current study, we investigated the use of microbubble ultrasound
      contrast agents bearing targeting ligands specific for molecular markers of tumor
      angiogenesis using high-frequency microultrasound imaging. A xenograft tumor
      model in the mouse was used to image vascular endothelial growth factor receptor
      2 (VEGFR-2) expression with microbubbles conjugated to an anti-VEGFR-2 monoclonal
      antibody or an isotype control. Microultrasound imaging was accomplished at a
      center frequency of 40 MHz, which provided lateral and axial resolutions of 40
      and 90 Im, respectively. The B-mode (two-dimensional mode) acoustic signal from
      microbubbles bound to the molecular target was determined by an ultrasound-based
      destruction-subtraction scheme. Quantification of the adherent microbubble
      fraction in nine tumor-bearing mice revealed significant retention of VEGFR-2
      targeted microbubbles relative to control-targeted microbubbles. These data
      demonstrate that contrast-enhanced microultrasound imaging is a useful method for
      assessing molecular expression of tumor angiogenesis in mice at high resolution.

PMID- 18092514
TI  - In vivo bioluminescence visualization of antitumor effects by human MUC1
      vaccination.
AB  - Recently, the use of a cancer deoxyribonucleic acid (DNA) vaccine encoding tumor
      associated antigens has emerged as an immunotherapeutic strategy. In this study,
      we monitored tumor growth inhibition by pcDNA3-hMUC1 immunization in mice using
      optical imaging. To determine the anti-hMUC1-associated immune response generated
      by pcDNA3.1 or pcDNA3-hMUC1, we determined the concentration of interferon-gamma
      (IFN-gamma) protein and CD8+IFN-gamma cell numbers among lymphocytes from the
      draining lymph nodes of mice immunized with pcDNA3.1 or pcDNA3-hMUC1. After
      subcutaneously injecting CT26/hMUC1-Fluc into mice immunized with pcDNA3-hMUC1,
      we monitored in vivo tumor growth inhibition using an optical imaging method. The
      concentration of IFN-gamma protein in pcDNA3-hMUC1 was higher than that of the
      pcDNA3.1 group (2.7 < or = 0.08 ng/mL and 1.6 +/- 0.07 ng/mL, respectively, p <
      .001. The number of hMUC1-associated CD8+IFN-gamma cells in pcDNA3-hMUC1
      immunized animals was 30-fold higher than in the pcDNA3.1 group. Bioluminescent
      images showed tumor growth inhibition in pcDNA3-hMUC1 immunized animals up to 25
      days after immunization. A good correlation (r2 = .9076: pcDNA3/hMUC1 group; r2 =
      .7428: pcDNA3.1 group) was observed between bioluminescence signals and tumor
      weights in two mice in each group. We conclude that optical bioluminescent
      imaging offers a useful means of monitoring the antitumor effects of cancer DNA
      immunization in living animals.

PMID- 18092515
TI  - In vivo time domain optical imaging of renal ischemia-reperfusion injury:
      discrimination based on fluorescence lifetime.
AB  - Fluorescence lifetime is an intrinsic parameter of the fluorescent probe,
      independent of the probe concentration but sensitive to changes in the
      surrounding microenvironment. Therefore, fluorescence lifetime imaging could
      potentially be applied to in vivo diagnostic assessment of changes in the tissue
      microenvironment caused by disease, such as ischemia. The aim of this study was
      to evaluate the utility of noninvasive fluorescence lifetime imaging in
      distinguishing between normal and ischemic kidney tissue in vivo. Mice were
      subjected to 60-minute unilateral kidney ischemia followed by 6-hour reperfusion.
      Animals were then injected with the near-infrared fluorescence probe Cy5.5 or
      saline and imaged using a time-domain small-animal optical imaging system. Both
      fluorescence intensity and lifetime were acquired. The fluorescence intensity of
      Cy5.5 was clearly reduced in the ischemic compared with the contralateral kidney,
      and the fluorescence lifetime of Cy5.5 was not detected in the ischemic kidney,
      suggesting reduced kidney clearance. Interestingly, the two-component lifetime
      analysis of endogenous fluorescence at 700 nm distinguished renal ischemia in
      vivo without the need for Cy5.5 injection for contrast enhancement. The average
      fluorescence lifetime of endogenous tissue fluorophores was a sensitive indicator
      of kidney ischemia ex vivo. The study suggests that fluorescence lifetime
      analysis of endogenous tissue fluorophores could be used to discriminate ischemic
      or necrotic tissues by noninvasive in vivo or ex vivo organ imaging.

PMID- 18092516
TI  - How reproducible is bioluminescent imaging of tumor cell growth? Single time
      point versus the dynamic measurement approach.
AB  - To determine the most robust and reproducible parameters for noninvasively
      estimating tumor cell burden in a murine model, we used real-time in vivo
      bioluminescent imaging to assess the growth kinetics and dissemination of
      luciferase-transfected Raji B-cell lymphoma. Bioluminescent signals were acquired
      every minute for 40 minutes after luciferin injection every other day post-tumor
      injection. The total 40-minute area under the curve (AUC) of photon intensity
      (photons/second) was calculated and compared with simplified fixed time point
      observations (every 5 minutes from 5 to 40 minutes after substrate injection).
      There was substantial variability in the shape of the time signal intensity
      curves at different stages of tumor growth in both the intravenous and
      subcutaneous models. The coefficient of variance in the AUC was 0.27
      (intravenous) and 0.36 (subcutaneous) as values determined by fitting the curve,
      whereas the 20-minute time point measurement varied at 0.29 (intravenous) and
      0.37 (subcutaneous). In both the subcutaneous and intravenous models, single time
      point measurements at 20 minutes had the highest correlation value with AUC. This
      simplified single time point measurement appears appropriate to estimate the
      total tumor burden in this model, but the substantial variance at each
      measurement must be considered in experimental designs.

PMID- 18092517
TI  - Bioluminescent mammalian cells grown in sponge matrices to monitor immune
      rejection.
AB  - The growth and bioluminescence of cells seeded in collagen and gelatin sponge
      matrices were compared in vitro under different conditions, and immune rejection
      was quantified and visualized directly in situ based on loss of bioluminescence
      activity. Mammalian cells expressing a Renilla luciferase complementary
      deoxyribonucleic acid (cDNA) were used to seed collagen and gelatin sponge
      matrices soaked in either polylysine or gelatin to determine optimal growth
      conditions in vitro. The sponges were incubated in tissue culture plates for 3
      weeks and received 2, 9, or 15 injections of coelenterazine. Measurements of
      bioluminescence activity indicated that gelatin sponges soaked in gelatin emitted
      the highest levels of light emission, multiple injections of coelenterazine did
      not affect light emission significantly, and light emission from live cells grown
      in sponges could be measured qualitatively but not quantitatively. Histologic
      analysis of sponge matrices cultured in vitro showed that cells grew best in
      gelatin matrices. Visualization of subcutaneously implanted sponges in mice
      showed accelerated loss of light emission in immunocompetent BALB/c mice compared
      with immunodeficient BALB/c-scid mice, which was associated with increased cell
      infiltration. Our results indicate that sponge matrices carrying bioluminescent
      mammalian cells are a valid model system to study immune rejection in situ.

PMID- 18092519
TI  - Etiology and management of posttraumatic malocclusions.
AB  - AIM: To establish the etiology of complications in patients undergoing treatment
      of maxillofacial trauma and justify the treatment of choice. METHODS: Four
      patients with posttraumatic occlusal irregularities comprised the subjects.
      RESULTS: Posttraumatic malocclusion has a complex etiology. The evaluation of the
      pretraumatic occlusal relationship is useful but not always possible. Anatomic
      repositioning of the fracture should be performed as soon as possible. Patients
      whose fractures are treated via maxillomandibular fixation who do not receive
      surgical reduction of a posttraumatic fracture have a greater possibility of
      later developing more severe dental and skeletal malocclusions. In cases treated
      via maxillomandibular fixation, Ivy loops should be avoided. CONCLUSION: When
      treating patients with maxillofacial trauma, care should be taken to
      counterbalance possible obstacles. This will result in a satisfactory
      posttraumatic occlusal scheme, without the need for orthodontic treatment or a
      second surgery.

PMID- 18092518
TI  - Bioluminescence imaging of vascular endothelial growth factor promoter activity
      in murine mammary tumorigenesis.
AB  - Vascular endothelial growth factor (VEGF) is a major inducer of angiogenesis. We
      generated a transgenic reporter mouse, VEGF-GL, in which an enhanced green
      fluorescent protein-luciferase fusion protein is expressed under the control of a
      human VEGF-A promoter. The VEGF-GL mouse exhibited intense bioluminescence
      throughout the body at 1 week of age. The signals rapidly declined to a
      relatively low level as the mice grew. The adult VEGF-GL mouse showed restricted
      bioluminescence to the areas undergoing wound healing. In contrast, the VEGF-GL
      mice, which were crossed with mouse mammary tumor virus-polyoma virus middle T
      antigen transgenic mammary tumor mice, exhibited prominent bioluminescence in the
      tumors, correlating with VEGF transcription. Tumor bioluminescence was observed
      in the bigenic mice as early as 8 weeks, before tumors were palpable, and the
      signals increased with tumor growth. In conclusion, the VEGF-GL mouse permits
      longitudinal and quantitative assessment of VEGF promoter activity in vivo. The
      model should facilitate understanding of the molecular controls and pathways that
      regulate VEGF transcription in vivo.

PMID- 18092520
TI  - Long-term outcome in a patient with a dentoskeletal open-bite malocclusion
      treated without extraction.
AB  - This case report describes the treatment of a patient with a Class II
      malocclusion with an anterior open bite. The patient, a girl 16 years of age, had
      a significant anteroposterior discrepancy and a high-angle tendency. Her face was
      convex, with competent lips. Intraorally she had an anterior open bite of 3 mm,
      space in the mandibular arch, and an overjet of 2 mm. High-pull headgear,
      anterior intermaxillary elastics, and appropriate wire bending were used to close
      the bite and to correct the anteroposterior dental relationship. Modification of
      a tongue thrust habit helped to correct this significant malocclusion and
      provided stability at 11 years posttreatment.

PMID- 18092521
TI  - Face mask therapy and conventional orthodontic treatment for anterior crossbite
      with cleft lip and palate: a case report.
AB  - AIM: To demonstrate a conventional orthodontic approach to anterior crossbite
      with unilateral cleft lip and palate. METHODS: Initially, maxillary expansion and
      face mask therapy was provided to widen the maxilla and improve the sagittal
      skeletal relation. Bone grafting to the maxillary left alveolar cleft then was
      performed, prior to treatment with a multibracket appliance. A multibracket
      appliance and intermaxillary elastics were used to align the dentition and
      establish a Class I relationship. RESULTS AND CONCLUSIONS: The combined
      orthodontic treatment of maxillary expansion, face mask therapy, bone grafting,
      and tooth alignment with a multibracket appliance resulted in a stable occlusion.
      The mandibular growth appeared after face mask therapy in adolescence; however,
      positive overjet and overbite were maintained throughout the retention phase.

PMID- 18092522
TI  - Mandibular corpus ostectomy for the correction of mandibular prognathism: a case
      report.
AB  - AIM: To present the dentofacial changes produced by mandibular body ostectomy in
      a female patient, 19 years of age, and the patient's 2-year follow-up records.
      SUBJECT AND TREATMENT: An increased lower facial height and a prominent chin,
      Angle Class III molar relationship, edentulous gaps in the first premolar regions
      of the mandible, with overjet and overbite values of -1 mm were observed.
      Radiographic evaluations revealed impaction of the maxillary right canine. The
      treatment plan included leveling and coordination of the arches, extraction of
      the maxillary left first premolar and the impacted canine, and a "rectangular"
      body ostectomy of 5 mm. RESULTS: Treatment lasted for 24 months. An increase of
      ANB was observed. Normal overjet and overbite were established. The posterior
      movement of the lower lip and soft and hard tissue points B and Pg were observed.
      No major changes were observed for the dentofacial structures at the 2-year
      follow-up visit. However, slight spacing at the ostectomy sites was present.
      CONCLUSION: The rectangular mandibular body ostectomy might be considered an
      alternative effective method for the correction of mandibular prognathism,
      particularly when the posterior occlusion is to remain unchanged and when
      edentulous gaps in the anterior region of the mandible are present.

PMID- 18092523
TI  - Effects of buccal shields on mandibular dental arch parameters: a clinical and
      cephalometric study.
AB  - The lip bumper is a vestibular functional appliance designed to extend
      bilaterally between the mandibular buccal tubes and contact the inner surface of
      the lower lip and cheeks. It functions to eliminate the pressure on the incisors,
      canines, and premolars, and to transmit distally directed forces to the molars.
      The purpose of this study was to evaluate the short-term effects of the buccal
      shield modification of the lip bumper design on various mandibular dental arch
      parameters, as well as on the inclination of the mandibular incisors. Included in
      the present study were 44 consecutively treated patients, consisting of 29
      females and 15 males from a private orthodontic practice. Student and paired t
      tests were used to evaluate the changes over time for the various measurements.
      The results indicated a significant (P < .0001) increase in all arch parameters
      measured. The greatest mean expansion was observed at the first (5.0 +/- 2.2 mm)
      and second (3.4 +/- 2.2 mm) premolar width measurements. Less expansion occurred
      in the intercanine (2.4 +/- 2.0 mm) and intermolar (2.4 +/- 2.6 mm) arch widths.
      Arch length increased on average 1.6 +/- 2.1 mm. These were significantly (P
      <.0001) greater than the normal age-related changes in the corresponding
      parameters.

PMID- 18092524
TI  - Orthodontic compensation in skeletal Class III malocclusion: a case report.
AB  - AIM: To describe the dentoskeletal changes occurring during treatment of a
      patient with a skeletal Class III malocclusion treated for orthodontic
      compensation at 10 years 4 months of age. METHODS: Rapid maxillary expansion was
      performed with a Hyrax appliance, Petit orthopedic face mask, high-pull chin cap,
      and bioprogressive fixed mechanics. RESULTS: The mechanics employed yielded
      downward and backward mandibular rotation (3 degrees of opening of the facial
      axis), advancement of the maxillary incisors, and retraction of the mandibular
      incisors. The result was satisfactory from both esthetic and functional
      standpoints, providing adequate overjet and overbite, and with stability at 5
      years posttreatment. CONCLUSION: The option for compensatory treatment of the
      skeletal Class III malocclusion without extractions and without orthognathic
      surgery might be a good option for young patients with good compliance,
      convergent facial pattern (brachyfacial), and with deep bite, since such occlusal
      characteristics allow the downward and backward mandibular rotation that is
      necessary for correction of this problem.

PMID- 18092525
TI  - A vertical cephalometric analysis.
AB  - Correctly assessing open-bite malocclusions has remained problematic because
      clinicians have not had entirely reliable methods of determining the exact amount
      of skeletal and dental contributions to the problem. A new cephalometric
      technique, the vertical cephalometric analysis, offers orthodontists a system
      that precisely identifies the percentage of skeletal and dentoalveolar components
      that open-bite patients have. The vertical cephalometric analysis offers a
      discriminating diagnostic method for evaluating, diagnosing, and treatment
      planning for patients with open bite. This technique will allow clinicians to
      classify patients with accuracy, as well as to establish prognoses and select
      therapies.

PMID- 18092526
TI  - Genetics or environment? A twin-method study of malocclusions.
AB  - AIM: To assess malocclusions susceptible to orthodontic prophylaxis by using the
      twin-method of analysis. MATERIAL AND METHODS: A comparative analysis of
      malocclusion was performed in monozygotic and dizygotic twins (164 twin-pairs: 90
      monozygotic pairs composed of 50 male and 40 female twin-pairs, and 74 dizygotic
      twin-pairs, with 46 male twin-pairs and 28 female twin-pairs). The zygotic twin
      status certainty was 98%, assigned using serologic and morphologic criteria
      together with dermatoglyphs. The Allen equation was applied for calculation of
      the hereditary coefficient for a given malocclusion. Significance established at
      P < .05 was used to analyze the data. RESULTS: Different distribution of within
      pair malocclusions depended upon the gender of the individuals; nevertheless, the
      differences with statistical significance occurred only in Class II males and
      females and males with crossbites. High frequency of within-pair malocclusion
      similarity (80% to 94%) characterized all groups except the dizygotic males,
      where the magnitude was 2 times less. The differing distribution of the
      dentoalveolar discrepancies was not statistically significant (P > .05). The
      frequency of within-pair similarity equaled 100% in monozygotic patients, while
      only 57% was found in dizygotic females. The hereditary coefficient had low or
      negative values-only in males did the examined values exceed 10%. CONCLUSION:
      This investigation showed that environmental factors account for more
      malocclusions than previously believed. This result encourages early intervention
      to intercept, disrupt, and diminish the effects of malocclusions.

PMID- 18092527
TI  - Things you want to know. Proper quality orthodontics vs. the new mechanical
      "systems".

PMID- 18092528
TI  - Xenodiagnosis: use of mosquitoes for the diagnosis of arboviral infections.
AB  - The arboviruses have a worldwide distribution and, mosquitoes and ticks
      contribute principally in their transmission. In the last two decades, arboviral
      diseases have been recognised due to their resurgence and spread in newer
      geographic areas. Surveys to determine the prevalence of arboviruses in any
      region largely depend on the isolation attempts from the arthropods along with
      the serosurveys. Xenodiagnosis means use of insects for the diagnosis of
      infectious diseases affecting human being. The present communication discusses
      the application of mosquitoes for propagation and assays of arboviruses, the
      technique of mosquito inoculation and importance of xenodiagnosis.

PMID- 18092529
TI  - Anopheles gambiae s.s. breeding in polluted water bodies in urban Lagos,
      southwestern Nigeria.
AB  - BACKGROUND & OBJECTIVE: Urban malaria is on the rise in Nigeria due to rapid
      industrialisation and developmental activities. A study was undertaken in Lagos,
      Nigeria to study the Anopheles breeding in polluted water bodies. METHODS:
      Anopheles larval breeding habitats were surveyed and water samples from 24 larval
      breeding sites from four strategic areas in urban Lagos were analysed. The
      relationship between eight abiotic variables (pH, dissolved oxygen, conductivity,
      hardness, nitrate, total dissolved solids, turbidity and oil) and density of
      Anopheles larvae were investigated. The levels of heavy metals (Zn, Co, Cu, Pb,
      Mn, Fe, Hg and Ni) pollution were analysed by Atomic Absorption
      Spectrophotometry. RESULTS: Morphological and PCR analysis of 2358 anopheline
      larvae revealed only the presence of two members of the Anopheles gambiae complex
      consisting of 93.1% Anopheles gambiae s.s. and 6.9% An. arabiensis. Multiple
      regression analysis revealed a significant association between occurrence of An.
      arabiensis larvae and two independent variables: pH and turbidity but not for An.
      gambiae s.s. The levels of three heavy metals: Fe, Cu and Pb from more than half
      of the sites surveyed were three times higher than the values obtained in natural
      breeding sites of An. gambiae s.s. from a rural area of Lagos. Over 85% of An.
      gambiae s.s. larvae were found in water bodies characterised by low dissolved
      oxygen (<3 mg/L), high conductivity (>900 uS/cm), turbidity (>180 FAU), oil (>11
      mg/L) and heavy metals: Fe, Cu, and Pb (>0.4 mg/L). INTERPRETATION & CONCLUSION:
      These results indicate that An. gambiae s.s. is adapting to a wide range of water
      pollution in this urban area. The survival of the mosquito in widespread polluted
      water bodies across Lagos metropolis could be responsible for the rise in the
      incidence of malaria.

PMID- 18092530
TI  - Morphological method for sexing anopheline larvae.
AB  - BACKGROUND & OBJECTIVES: Most of autocidal control of malaria vectors relies on
      the rearing and release of large numbers of sterile male into a wild population
      and it would be crucial to separate the males from females before release. This
      could result in enormous economic benefits in the mass rearing and raise the
      efficiency of the field operations. The development of genetic sexing of
      mosquitoes, enabling the release of males only, but impairing the overall fitness
      of the released insect has been considered greatly. Here we report on a
      morphological sexing method for the preferential diagnosis and separation of
      males in late III and IV instar larvae for the mosquitoes Anopheles stephensi
      Liston and An. culicifacies s.l. (Diptera: Culicidae), the principal vectors of
      human malaria in Asia and Indian subcontinent. METHODS: Male mosquitoes are
      identified by their tube like organ at the 9th abdomen segment which originates
      from segment parallel to the spiracles. Length and width of this organ is
      measured as 66.66 +/- 9.5 and 14.3 +/- 1.5 microm respectively. The whole length
      of the organ is 201.63 +/- 23.4 microm. Two fried eggs in the anterior portion of
      the segment are apparent in males. The length of tube in female is shorter than
      the male (almost half of the length--37.95 +/- 4.0 microm), its width is slightly
      stout and wider than the male (16.72 +/- 1.4 microm). Two fried eggs in the
      anterior portion of the segment are absent. After separation of live male larvae
      by those characteristics, they were transferred into the trays and emerged adults
      were identified to ascertain correct identification of sex. RESULTS: All the
      larvae with male organs developed into male adults with hairy antennae and club
      shaped palpi, whereas all the female larvae developed into adult females.
      INTERPRETATION & CONCLUSION: The sex separation at the larval stage will provide
      a clue for embryonic origin of sex organs, insecticide selection at the larval
      stage, sex related genes, male sterility and other measures.

PMID- 18092531
TI  - Prevalence of malaria as co-infection in HIV-infected individuals in a malaria
      endemic area of southeastern Nigeria.
AB  - BACKGROUND & OBJECTIVE: The present study was conducted on the prevalence of
      malaria as co-infection amongst 'asymptomatic HIV' and 'symptomatic HIV' subjects
      to see if such prevalence deviated from that commonly reported in apparently
      health individuals in same locality. METHODS: A prospective study that involved
      196 participants grouped according to their HIV status as: 'asymptomatic HIV
      seropositive group' (n = 101); 'symptomatic HIV seropositive group' (n = 48) and
      'control HIV-seronegative group (n = 47). Blood samples collected from the
      participants were used for double HIV screening by rapid immunoassay technique
      and immunochromatographic technique, and for the diagnosis of Plasmodium
      falciparum malaria using rapid P. falciparum antigen detection method. RESULTS:
      The result showed that the prevalence of P. falciparum malaria as a co-infection
      amongst the asymptomatic HIV seropositive group was 12 (11.8%) and amongst the
      symptomatic HIV seropositive group was 16 (33.3%). However, the prevalence rate
      of P. falciparum malaria amongst the control HIV seronegative group was 5 (10.6%)
      and the combined burden of P. falciparum malaria amongst both groups of HIV
      seropositives was 28 (18.9%). INTERPRETATION & CONCLUSION: The present study
      observed different prevalence rates of P. falciparum malaria amongst the three
      groups. The prevalence was tripled in symptomatic HIV seropositive group. This
      shows a clear departure from possible obtainable prevalence of malaria infection
      alone in this malaria endemic area. Due to the mortality rates associated with
      malaria infection in an endemic area, it may be necessary that routine malaria
      screening be adopted as part of the management policy to check the co-infection.

PMID- 18092532
TI  - Change of serum transferrin receptor due to malarial infection, an experiment in
      Plasmodium gallinaceum infected chicken model.
AB  - BACKGROUND & OBJECTIVES: The serum transferrin receptor (sTfR) concentration in
      an individual reflects the extent of erythropoietic activity and is considered as
      an useful marker of iron deficiency independent of concurrent inflammation or
      infection. However, data on the impact of malaria on this parameter are
      ambiguous. METHODS: Here we performed an animal experiment to study the
      chronological change of serum transferrin receptor due to infection of Plasmodium
      gallinaceum. In this pilot study, we performed control experimental infection of
      P. gallinaceum to four newborn chicken from the same batch. We collected the
      venous blood samples from all chicken on Day 7 and 14. All samples were analysed
      for sTfR level by the immunoturbidimetric assay. RESULTS: The average level of
      sTfR level of the control chicken was 1.24 +/- 1.58 mg/L (range 0.18 to 3.52
      mg/L). The average level of sTfR level of the experimental chicken on Day 7 was
      5.42 +/- 2.19 mg/L (range 3.22 to13.94 mg/L). CONCLUSION: Although the trend of
      increase was observed but no significance was observed (p > 0.05). The results
      from this pilot study can be a good basic data for the further study in this
      area.

PMID- 18092533
TI  - Laboratory studies on the effect of inorganic fertilizers on survival and
      development of immature Culex quinquefasciatus (Diptera: Culicidae).
AB  - BACKGROUND & OBJECTIVES: Studies were conducted to determine the effect of
      ammonium sulfate (AM) and muriate of potash (MOP) fertilizers on survival and
      development of immature stages of Culex quinquefasciatus Say, a major vector of
      Bancroftian filariasis in Africa. METHODS: Twenty I instar larvae each were added
      in four doses of each fertilizer dissolved in one litre of deionised water and in
      one litre of deionised water as a control in replicates of five. The larvae were
      monitored every morning throughout their life and the numbers of each instar
      surviving were recorded. The experiments were discontinued when all the larvae
      had died or emerged into adults. RESULTS: An analysis of variance test and
      Tukey's HSD test revealed a significant impact of fertilizers on survival and
      development of aquatic stages of Cx. quinquefasciatus. Ammonium sulfate accounted
      for up to 40% mortality rate, and one week delay in development time and this
      effect was both instar and dose dependent. None of the MOP dosages had
      significant impact on survival of immatures of Cx. quinquefasciatus and only the
      higher dosages showed significant impact on development time but in significantly
      lower magnitudes compared with similar dosages of ammonium sulfate.
      INTERPRETATION & CONCLUSION: These findings demonstrate the toxic effect of
      fertilizers on immature stages of Cx. quinquefasciatus contrary to field
      observations.

PMID- 18092534
TI  - Age as a risk factor for thrombocytopenia and anaemia in children treated for
      acute uncomplicated falciparum malaria.
AB  - BACKGROUND & OBJECTIVES: Anaemia is commonly observed in children with malaria,
      but reports on leucocyte and platelet count abnormalities associated with malaria
      are inconsistent. This study examined the effect of age, gender, parasite density
      and temperature on haematological parameters in children with acute uncomplicated
      malaria. METHODS: Haematological parameters were determined in children with
      acute uncomplicated malaria, and these were correlated with age, sex, temperature
      and parasite density. Statistical analysis was done using SAS 9.1. RESULTS: Six
      hundred and ninety five children with acute uncomplicated malaria participated in
      the study. The mean age was 51.7 months +/- 33.8. At presentation, anaemia
      occurred in 43.8% of the patients and children <5 yr had a significantly lower
      haematocrit (28.4% +/- 4.8) than that of older children (32.8% +/- 4.8) (p
      <0.001), but the haematocrit was not significantly different by days 14 and 28.
      There was no difference between both sexes. Leucocytosis was more frequently seen
      than leucopenia (9.5% vs 3%). Thrombocytopenia was found in 59.3% of enrolled
      patients. More than half of the patients with thrombocytopenia had recovered by
      Day 28. Baseline platelet count was related to Day 14 (r = 0.6, p < 0.0001) and
      Day 28 (r = 0.2, p = 0.0015) and the haematocrit on Day 28 (r = 0.12, p =
      0.00197). Platelet count showed no correlation with temperature, parasite density
      and leucocyte count. Haematocrit correlated with age (r = 0.4, p < 0.0001); but
      not with parasite density or temperature. Leucocyte count showed no correlation
      with age or parasite density. CONCLUSION: While thrombocytopenia was the most
      common haematological finding and may be of diagnostic importance, anaemia and
      leucocytosis were more common in the under fives.

PMID- 18092535
TI  - ELISA as an alternative tool for epidemiological surveillance for dengue in
      mosquitoes: a report from Thailand.
AB  - BACKGROUND & OBJECTIVES: Dengue fever (DF), dengue hemorrhagic fever (DHF) and
      dengue shock syndrome (DSS) are the re-emerging infectious diseases caused by the
      four serotypes of dengue (DEN) virus, type 1 to 4, belonging to the family
      Flaviviridae and genus Flavivirus. In the absence of a safe and effective mass
      immunisation, the prevention and control of dengue outbreaks depend upon the
      surveillance of cases and mosquito vector. The aim of this work is to test enzyme
      linked immunosorbent assay (ELISA) tool for the virological surveillance of
      dengue. METHODS: Virus-infected Aedes mosquitoes were collected from the field in
      order to serve as an early warning monitoring tool for dengue outbreaks. In a
      prospective field study conducted from April to September 2000, female adult
      Aedes mosquitoes were caught from selected dengue-sensitive area in Chombung
      district, Ratchaburi province and assayed by ELISA. RESULT: Approximately 18.3%
      were found positive for dengue virus. CONCLUSION: This can imply that ELISA can
      be an alternative tool for epidemiological surveillance for dengue in mosquitoes.

PMID- 18092536
TI  - Effect of mass drug administration programme on microfilaria carriers in East
      Godavari district of Andhra Pradesh.

PMID- 18092537
TI  - Dynamics of malaria in Bikaner, Rajasthan, India (1975-2006).

PMID- 18092538
TI  - Impact of maternal Plasmodium falciparum malaria and haematological parameters on
      pregnancy and its outcome in southeastern Nigeria.

PMID- 18092540
TI  - Trends in cancer incidence by deprivation, England and Wales, 1990-2002.
AB  - This article examines trends in cancer incidence by deprivation in England and
      Wales, and at the Government Office Region (GOR) and Wales level over the period
      1990-2002. The aim is to show whether the deprivation gap in cancer incidence
      between patients living in the least deprived areas and those in the most
      deprived has widened or narrowed over time for the three main cancers, breast
      (female), prostate and lung cancer. The results show that the deprivation gap in
      lung cancer incidence has widened in the majority of GORs and Wales, particularly
      in males. For prostate cancer, where incidence was generally higher among those
      living in the least deprived areas, the deprivation gap has also widened in the
      majority of GORs and Wales.

PMID- 18092539
TI  - Social inequalities in adult male mortality by the National Statistics Socio
      Economic Classification, England and Wales, 2001-03.
AB  - This article reports social inequalities in mortality in men aged 25-64 years in
      England and Wales, in the period 2001-03 using unlinked data sources and 2001-04
      using linked data sources. It represents the first official analysis of premature
      mortality by the final version of the National Statistics Socio-economic
      Classification introduced in 2001, and updates the tradition of decennial
      reporting of mortality by socio-economic status. These results set a benchmark
      for inequalities in mortality in men of this age, providing insights into the
      impacts of different social and occupational circumstances in the early 21st
      Century and enabling future monitoring. The Office for National Statistics
      intends to extend this work to examine inequalities to mortality in females of
      the same age, in causes of death and by Government Office Region.

PMID- 18092541
TI  - Cancer survival indicators by Cancer Network: a methodological perspective.
AB  - Cancer Networks are responsible for the management of cancer services in England.
      They are, in principle, logical units for the analysis of cancer survival, since
      for most patients, the entire pathway of referral, diagnosis and treatment is
      likely to be contained within the territory of a Cancer Network. This study
      investigates the implications of using each patient's Cancer Network of residence
      as the geographic basis of cancer survival indicators for the Department of
      Health and the National Health Service. Incidence data from the National Cancer
      Registry were used to estimate survival from cancers of the breast and colon
      diagnosed in adults during 1996-98. Survival estimates varied little between
      Cancer Networks. They were generally stable over time. We conclude that Cancer
      Networks are suitable geographic units for the analysis of cancer survival as a
      NHS performance indicator.

PMID- 18092543
TI  - Life expectancy at birth and at age 65 65 by local areas in the United Kingdom
      2004-06.

PMID- 18092542
TI  - Deaths related to drug poisoning in England and Wales, 2002-06.

PMID- 18092544
TI  - Infant and perinatal mortality by social and biological factors, 2006.

PMID- 18092545
TI  - Infant and perinatal mortality 2006: health areas, England and Wales.

PMID- 18092546
TI  - Mortality statistics 2005: general.

PMID- 18092548
TI  - Weight-loss programs need health plan support.

PMID- 18092547
TI  - Deaths: leading causes for 2004.
AB  - OBJECTIVES: This report presents final 2004 data on the 10 leading causes of
      death in the United States by age, race, sex, and Hispanic origin. Leading causes
      of infant, neonatal, and postneonatal death are also presented. This report
      supplements the annual report of final mortality statistics. METHODS: Data in
      this report are based on information from all death certificates filed in the 50
      states and the District of Columbia in 2004. Causes of death classified by the
      International Classification of Diseases, Tenth Revision (ICD-10) are ranked
      according to the number of deaths assigned to rankable causes. RESULTS: In 2004,
      the 10 leading causes of death were (in rank order) Diseases of heart; Malignant
      neoplasms; Cerebrovascular diseases; Chronic lower respiratory diseases;
      Accidents (unintentional injuries); Diabetes mellitus; Alzheimer's disease;
      Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and
      Septicemia and accounted for about 78 percent of all deaths occurring in the
      United States. Differences in the ranking are evident by age, sex, race, and
      Hispanic origin. Leading causes of infant death for 2004 were (in rank order)
      Congenital malformations, deformations and chromosomal abnormalities; Disorders
      related to short gestation and low birth weight, not elsewhere classified; Sudden
      infant death syndrome; Newborn affected by maternal complications of pregnancy;
      Accidents (unintentional injuries); Newborn affected by complications of
      placenta, cord and membranes; Respiratory distress of newborn; Bacterial sepsis
      of newborn; Neonatal hemorrhage; and Diseases of the circulatory system.
      Important variation in the leading causes of infant death is noted for the
      neonatal and postneonatal periods.

PMID- 18092550
TI  - Compensation monitor. P4P--giving rewards at the practice level.

PMID- 18092549
TI  - PBMs agree to disclose what they pay for drugs.

PMID- 18092551
TI  - The evolving health plan.

PMID- 18092552
TI  - New imaging controls strict, but may be easier on doctors.

PMID- 18092553
TI  - Plans unsettled by prospect of Democrat in White House.

PMID- 18092554
TI  - Blues build on CMS program to boost hospital quality.

PMID- 18092555
TI  - Evolution of TennCare yields valuable lessons.

PMID- 18092556
TI  - Cryoablation for atrial flutter requires no anesthesia.

PMID- 18092557
TI  - Managed care outlook. 2008 cost hike should be less than 2007.

PMID- 18092560
TI  - State-of-the-science on postacute rehabilitation: setting a research agenda and
      developing an evidence base for practice and public policy. An introduction.
AB  - The Rehabilitation Research and Training Center on Measuring Rehabilitation
      Outcomes and Effectiveness, along with academic, professional, provider,
      accreditor, and other organizations, sponsored a 2-day State-of-the-Science of
      Postacute Rehabilitation Symposium in February 2007. The aim of this symposium
      was to serve as a catalyst for expanded research on postacute care (PAC)
      rehabilitation so that health policy is founded on a solid evidence base. The
      goals were to (a) describe the state of our knowledge regarding utilization,
      organization, and outcomes of postacute rehabilitation settings, (b) identify
      methodologic and measurement challenges to conducting research, (c) foster the
      exchange of ideas among researchers, policy makers, industry representatives,
      funding agency staff, consumers, and advocacy groups, and (d) identify critical
      questions related to setting, delivery, payment, and effectiveness of
      rehabilitation services. Plenary presentation and state-of-the-science summaries
      were organized around 4 themes: (a) the need for improved measurement of key
      rehabilitation variables and methods to collect and analyze this information, (b)
      factors that influence access to postacute rehabilitation care, (c) similarities
      and differences in quality and quantity of services across PAC settings, and (d)
      effectiveness of postacute rehabilitation services. The full set of symposium
      articles, including recommendations for future research, appear in Archives of
      Physical Medicine and Rehabilitation.

PMID- 18092559
TI  - Postoperative spinal wound infections and postprocedural diskitis.
AB  - BACKGROUND/OBJECTIVE: Postprocedural infections are a significant cause of
      morbidity after spinal interventions. METHODS: Literature review. An extensive
      literature review was conducted on postprocedural spinal infections. Relevant
      articles were reviewed in detail and additional case images were included.
      RESULTS: Clinical findings, laboratory markers, and imaging modalities play
      important roles in the detection of postprocedural spinal infections. Treatment
      may range from biopsy and antibiotics to multiple operations with complex
      strategies for soft tissue management. CONCLUSIONS: Early detection and
      aggressive treatment are paramount in managing postprocedural spinal infections
      and limiting their long-term sequelae.

PMID- 18092558
TI  - Pain after spinal cord injury: an evidence-based review for clinical practice and
      research. Report of the National Institute on Disability and Rehabilitation
      Research Spinal Cord Injury Measures meeting.
AB  - BACKGROUND/OBJECTIVES: To examine the reliability, validity, sensitivity, and
      practicality of various outcome measures for pain after spinal cord injury (SCI),
      and to provide recommendations for specific measures for use in clinical trials.
      DATA SOURCES: Relevant articles were obtained through a search of MEDLINE,
      EMBASE, CINAHL, and PubMed databases from inception through 2006. STUDY
      SELECTION: The authors performed literature searches to find articles containing
      data relevant to the reliability and validity of each pain outcome measure in SCI
      and selected non-SCI populations. DATA EXTRACTION: After reviewing the articles,
      an investigator extracted information utilizing a standard template. A second
      investigator reviewed the chosen articles and the extracted pertinent information
      to confirm the findings of the first investigator. DATA SYNTHESIS: Taking into
      consideration both the quantity and quality of the studies analyzed, judgments on
      reliability and validity of the measures were made by the two investigators.
      Based upon these judgments, recommendations were formulated for use of specific
      measures in future clinical trials. In addition, for a subset of measures a
      voting process by a larger group of SCI experts allowed formulation of
      recommendations including determining which measures should be incorporated into
      a minimal dataset of measures for clinical trials and which ones need revision
      and further validity and reliability testing before use. CONCLUSIONS: A 0-10
      Point Numerical Rating Scale (NRS) is recommended as the outcome measure for pain
      intensity after SCI, while the 7-Point Guy/Farrar Patient Global Impression of
      Change (PGIC) scale is recommended as the outcome measure for global improvement
      in pain. The SF-36 single pain interference question and the Multidimensional
      Pain Inventory (MPI) or Brief Pain Inventory (BPI) pain interference items are
      recommended as the outcome measures for pain interference after SCI. Brush or
      cotton wool and at least one high-threshold von Frey filament are recommended to
      test mechanical allodynia/hyperalgesia while a Peltier-type thermotester is
      recommended to test thermal allodynia/hyperalgesia. The International Association
      for the Study of Pain (IASP) or Bryce-Ragnarsson pain taxonomies are recommended
      for classification of pain after SCI, while the Neuropathic Pain Scale (NPS) is
      recommended for measuring change in neuropathic pain and the Leeds Assessment of
      Neuropathic Symptoms and Signs (LANSS) for quantitating neuropathic and
      nociceptive pain discrimination.

PMID- 18092561
TI  - Low-frequency fatigue in individuals with spinal cord injury.
AB  - BACKGROUND/OBJECTIVE: This study examined magnitude and recovery of low-frequency
      fatigue (LFF) in the quadriceps after electrically stimulated contractions in
      spinal cord-injured (SCI) and able-bodied subjects. SUBJECTS: Nine SCI (ASIA A-C,
      levels C5-T9, injured 13.6 +/- 12.2 years) and 9 sedentary able-bodied subjects
      completed this study. METHODS: Fatigue was evoked in 1 thigh, and the nonfatigued
      leg served as a control. The fatigue test for able-bodied subjects lasted 15
      minutes. For SCI, stimulation was adjusted so that the relative drop in force was
      matched to the able-bodied group. Force was assessed at 20 (P20) and 100 Hz
      (P100), and the ratio of P20/P100 was used to evaluate LFF in thighs immediately
      after, at 10, 20, and 60 minutes, and at 2, 4, 6, and 24 hours after a fatigue
      test. RESULTS: The magnitude of LFF (up to 1 hour after fatigue) was not
      different between able-bodied and patients with SCI. However, recovery of LFF
      over 24 hours was greater in able-bodied compared with patients with SCI in both
      the experimental (P < 0.001) and control legs (P < 0.001). The able-bodied group
      showed a gradual recovery of LFF over time in the experimental leg, whereas the
      SCI group did not. CONCLUSIONS: These results show that individuals with SCI are
      more susceptible to LFF than able-bodied subjects. In SCI, simply assessing LFF
      produced considerable LFF and accounted for a substantial portion of the
      response. We propose that muscle injury is causing the dramatic LFF in SCI, and
      future studies are needed to test whether "fatigue" in SCI is actually confounded
      by the effects of muscle injury.

PMID- 18092562
TI  - Provocative stimulation of growth hormone: a monozygotic twin study discordant
      for spinal cord injury.
AB  - BACKGROUND/OBJECTIVE: A blunted growth hormone (GH) response to provocative
      testing and/or low levels of plasma insulin-like growth factor-I (IGF-I) have
      been reported in persons with spinal cord injury (SCI). A reduction in activity
      of the GH-IGF-I axis may have deleterious effects on body composition and
      function. Provocative testing for GH stimulation was performed to determine the
      response in monozygotic twins that were discordant for SCI. METHODS: GH
      stimulation testing was performed by the administration of intravenous arginine.
      RESULTS: Nine SCI twins with paraplegia, a mean age of 39 +/- 9 years, and
      duration of injury of 14 +/- 9 years were studied. The twins with SCI had a
      significantly lower body mass index than non-SCI twins (22.5 +/- 4.0 vs 25.1 +/-
      4.2 kg/m2; P < 0.05); percent fat mass was greater in the twins with SCI (30 +/-
      11% vs 22 +/- 10%; P < 0.05). Baseline serum GH was correlated with percent fat
      only in the SCI twins. The response to GH provocative stimulation was less in the
      twins with SCI: peak GH response was 5.8 +/- 6.6 vs 13.0 +/- 7.3 ng/mL (P <
      0.05), and sum GH response was 15.7 +/- 15.6 vs 30.2 +/- 17.3 ng/mL (P = 0.06).
      Although baseline serum GH was correlated with stimulated response in the SCI
      twins, this relationship was not found in the non-SCI twins. Adiposity was
      positively related to the provocative serum GH response in twins with SCI rather
      than negatively related, as noted in the non-SCI twins. CONCLUSIONS: This study
      confirms and extends prior work that reported a reduction in stimulated GH
      release in persons with SCI, which was related to baseline values.

PMID- 18092563
TI  - Clinical significance of abnormal electrocardiographic findings in individuals
      aging with spinal injury and abnormal lipid profiles.
AB  - BACKGROUND: Cardiovascular risk factors are common in individuals with chronic
      spinal cord injury (SCI), and their prevalence increases with age. The actual
      prevalence of overt cardiovascular disease (CVD) in this population has not been
      well established. METHODS: Electrocardiograms (ECGs) were examined for
      abnormalities in 43 individuals with abnormal lipid profiles being followed in
      the outpatient SCI clinic of our institution. The mean age of the study
      population of predominantly men was 43 +/- 9.9 years and the mean duration of
      injury 16.6 +/- 8 years. RESULTS: ECG abnormalities were common and present in
      60.5% of participants. ST-T wave abnormalities were the most commonly observed
      (35%). Evidence of previous myocardial infarction was present in 7% of all
      individuals and in 12% of those with ECG abnormalities. The only clinical
      parameter differentiating the group with normal vs abnormal ECG was the duration
      of injury (19.5 +/- 8 y vs 12 +/- 5 y; P = 0.0026). Analysis of variance showed
      that injury duration was the sole predictor of abnormal ECG with 68% accuracy (P
      = 0.006). Among those with ECG abnormalities, although no significant differences
      were detected between those with and without evidence of previous myocardial
      infarction, mean total cholesterol and low-density lipoprotein were higher, and
      mean high-density lipoprotein was lower. Mean age and injury duration were
      greater in those with evidence of previous myocardial infarction. CONCLUSION:
      Although age is an important risk factor for CVD in the population of individuals
      without disabilities, injury duration is at least as important as age in those
      with SCI. Our findings support the recommendation that individuals with SCI and
      abnormal lipids should be screened for CVD regardless of age.

PMID- 18092564
TI  - Health care costs for patients with chronic spinal cord injury in the Veterans
      Health Administration.
AB  - BACKGROUND/OBJECTIVE: Recurring annual costs of caring for patients with chronic
      spinal cord injury (SCI) is a large economic burden on health care systems, but
      information on costs of SCI care beyond the acute and initial postacute phase is
      sparse. The objective of this study was to establish a frame of reference and
      estimate of the annual direct medical costs associated with health care for a
      sample of patients with chronic SCI (ie, > 2 years after injury). METHODS:
      Patients were recruited from 3 Veterans Health Administration (VHA) SCI
      facilities; baseline patient information was cross-referenced to the Decision
      Support System (DSS) National Data Extracts (NDE) to obtain patient-specific
      health care costs in VHA. Descriptive statistical analysis of annual DSS-NDE cost
      of patients with SCI (N = 675) for fiscal year (FY) 2005 by level and
      completeness of injury was conducted. RESULTS: Total (inpatient and outpatient)
      annual (FY 2005) direct medical costs for 675 patients with SCI exceeded $14.47
      million or $21,450 per patient. Average annual total costs varied from $28,334
      for cervical complete SCI to $16,792 for thoracic incomplete SCI. Two hundred
      thirty-three of the 675 patients with SCI who were hospitalized over the study
      period accounted for a total of 378 hospital discharges, costing in excess of
      $7.19 million. This approximated a cost of outpatient care received of $7.28
      million for our entire sample. CONCLUSIONS: The comprehensive nature of health
      care delivery and related cost capture for people with chronic SCI in the VHA
      provided us the opportunity to accurately determine health care costs for this
      population. Future SCI postacute care cost analyses should consider case-mix
      adjusting patients at high risk for rehospitalization.

PMID- 18092565
TI  - Hemodynamic parameters and timing of surgical decompression in acute cervical
      spinal cord injury.
AB  - BACKGROUND/OBJECTIVES: To evaluate the relationship between the severity of
      cervical spinal cord injury (SCI) (American Spinal Injury Association [ASIA]
      grade), presence of neurogenic shock, and timing of surgical intervention. This
      is a post-hoc analysis from the Sygen multicenter randomized controlled trial.
      METHODS: Blood pressure (BP) and heart rate (HR) data were collected when
      patients were first assessed in the emergency room (Time A) and at the time of
      randomization (Time B). Individuals were subdivided by ASIA grade and by the
      level of the systolic BP (SBP). RESULTS: Only individuals with cervical SCI from
      the Sygen trial (n = 577) were evaluated. Severe complete SCI (ASIA grade = A)
      was established in 57% of these patients. A total of 74 (13%) patients with
      neurogenic shock (SBP < 90 mmHg) at Time A were identified. The SBP increased
      significantly from Time A to Time B (P < 0.0001). The median time from SCI to
      surgical intervention, for ASIA A, was 80.9 hours for patients with initial SBP <
      90 mmHg and 58 hours for patients with initial SBP > or = 90 mmHg (P = 0.025).
      Multivariable analysis after adjusting for confounders revealed a statistically
      significant difference in the time to surgical intervention based on SBP for ASIA
      A (P = 0.026), yet not for ASIA B or C/D. CONCLUSIONS: The presence of neurogenic
      shock was associated with a delay in the timing of surgical intervention in
      patients with cervical SCI. Detailed evaluation of autonomic dysfunctions
      following SCI including cardiovascular instability could improve our
      understanding of the complexities of clinical presentations and possible
      neurological outcomes.

PMID- 18092566
TI  - Pilot evaluation of functional questionnaire for predicting ability of patients
      with tetraplegia to self-catheterize after continent diversion.
AB  - BACKGROUND/OBJECTIVES: Creation of a continent catheterizable stoma has
      dramatically improved the ability of the patient with spinal cord injury to
      perform clean intermittent catheterization (CIC). However, not all patients are
      good candidates for this procedure. To aid in patient evaluation, we propose the
      use of a functional questionnaire to predict a candidate's ability to negotiate a
      continent catheterizable stoma. METHODS: A published functional questionnaire was
      adapted to assess the self-perceived ability to perform upper extremity tasks
      similar to those involved in the manipulation of catheter. Tetraplegic patients
      who had undergone creation of a content catheterizable stoma were given the
      questionnaire and asked to describe demographics, method of catheterization,
      motivational factors, and satisfaction with the procedure. RESULTS: Subjects
      varied in age (23-36 years) and level of impairment (C4-C6). Functional scores
      correlated with level of injury. Of the 4 women and 1 man who responded, only 2
      were able to self-catheterize before diversion. Their catheterization times
      decreased significantly after creation of a continent stoma. Two patients unable
      to perform CIC preoperatively were able to perform CIC postoperatively. The
      patient with the lowest score was unable to perform CIC preoperatively or
      postoperatively. All were satisfied with outcome after diversion. CONCLUSIONS: In
      our small cohort, a low functional score was associated with inability to perform
      CIC after continent diversion. Administration of this questionnaire to a larger
      spinal cord injury population should aid in selecting appropriate candidates for
      the creation of a continent catheterizable stoma.

PMID- 18092567
TI  - Measuring tissue perfusion during pressure relief maneuvers: insights into
      preventing pressure ulcers.
AB  - BACKGROUND/OBJECTIVE: To study the effect on tissue perfusion of relieving
      interface pressure using standard wheelchair pushups compared with a mechanical
      automated dynamic pressure relief system. DESIGN: Repeated measures in 2
      protocols on 3 groups of subjects. PARTICIPANTS: Twenty individuals with motor
      complete paraplegia below T4, 20 with motor-complete tetraplegia, and 20 able
      bodied subjects. METHODS: Two 1-hour sitting protocols: dynamic protocol, sitting
      configuration alternated every 10 minutes between a normal sitting configuration
      and an off-loading configuration; wheelchair pushup protocol, normal sitting
      configuration with standard wheelchair pushup once every 20 minutes. MAIN OUTCOME
      MEASURES: Transcutaneous partial pressures of oxygen and carbon dioxide measured
      from buttock overlying the ischial tuberosity and interface pressure measured at
      the seat back and buttocks. Perfusion deterioration and recovery times were
      calculated during changes in interface pressures. RESULTS: In the off-loading
      configuration, concentrated interface pressure during the normal sitting
      configuration was significantly diminished, and tissue perfusion was
      significantly improved. Wheelchair pushups showed complete relief of interface
      pressure but incomplete recovery of tissue perfusion. CONCLUSIONS: Interface
      pressure analysis does not provide complete information about the effectiveness
      of pressure relief maneuvers. Measures of tissue perfusion may help establish
      more effective strategies. Relief achieved by standard wheelchair pushups may not
      be sufficient to recover tissue perfusion compromised during sitting; alternate
      maneuvers may be necessary. The dynamic seating system provided effective
      pressure relief with sustained reduction in interface pressure adequate for
      complete recovery of tissue perfusion. Differences in perfusion recovery times
      between subjects with spinal cord injury (SCI) and controls raise questions about
      the importance of changes in vascular responses to pressure after SCI.

PMID- 18092570
TI  - MS-DRG system offers opportunities, potential changes in the bottom line.
      Accurately documenting severity of illness is the key to success.

PMID- 18092569
TI  - Heterotopic ossification of the vocal cords after spinal cord injury.
AB  - BACKGROUND/OBJECTIVE: To report a rare complication of heterotopic ossification
      of the vocal cords after spinal cord and multiple organ injuries. STUDY DESIGN:
      Case report. SETTING: Acute rehabilitation in the Department of Neurologic
      Rehabilitation. RESULTS: A 55-year-old patient sustained spinal cord injury and
      multitrauma after falling from a height. Approximately 3 months later, after
      weaning from mechanical ventilation, plugging of the cannula resulted in severe
      stridor indicating upper airway obstruction. A computed tomography scan showed
      bilateral vocal cord fixation in a para-median position, with hyperossification
      of the vocal processes of the arytenoids. Direct laryngoscopy revealed
      interarytenoid ossification, and sawing through the ossification resulted in
      remobilization of the vocal cords enabling decannulation. CONCLUSIONS:
      Heterotopic ossification of the vocal cords was found to be an early complication
      of acute spinal cord injury and multiple trauma. This rare complication should be
      considered in the differential diagnosis of patients showing signs of upper
      airway obstruction.

PMID- 18092568
TI  - Evaluation of neurologic deficit without apparent cause: the importance of a
      multidisciplinary approach.
AB  - BACKGROUND/OBJECTIVE: A patient presenting with an acute neurologic deficit with
      no apparent etiology presents a diagnostic dilemma. A broad differential
      diagnosis must be entertained, considering both organic and psychiatric causes.
      METHODS: A case report and thorough literature review of acute paraplegia after a
      low-energy trauma without a discernible organic etiology. RESULTS: Diagnostic
      imaging excluded any bony malalignment or fracture and any abnormality on
      magnetic resonance imaging. When no organic etiology was identified, a
      multidisciplinary approach using neurology, psychiatry, and physical medicine and
      rehabilitation services was applied. Neurophysiologic testing confirmed the
      absence of an organic disorder, and at this juncture, diagnostic efforts focused
      on identifying any psychiatric disorder to facilitate appropriate treatment for
      this individual. The final diagnosis was malingering. CONCLUSIONS: The full
      psychiatric differential diagnosis should be considered in the evaluation of any
      patient with an atypical presentation of paralysis. A thorough clinical
      examination in combination with the appropriate diagnostic studies can
      confidently exclude an organic disorder. When considering a psychiatric disorder,
      the differential diagnosis should include conversion disorder and malingering,
      although each must remain a diagnosis of exclusion. Maintaining a broad
      differential diagnosis and involving multiple disciplines (neurology, psychiatry,
      social work, medical specialists) early in the evaluation of atypical paralysis
      may facilitate earlier diagnosis and initiation of treatment for the underlying
      etiology.

PMID- 18092571
TI  - Get physicians in on improving documentation. Tailor education efforts to
      facility's needs, case mix.

PMID- 18092572
TI  - Quality initiative slashes occurrences of VAP. Interdisciplinary team changed
      practices in ICU.

PMID- 18092573
TI  - Critical path network. Hospitalwide throughput initiative lowers diversion by
      71%. ED CMs, admissions nurse speed process.

PMID- 18092574
TI  - Critical path network. No increase in appeals reported with new IM rules.
      Proactive discharge planning good prevention.

PMID- 18092576
TI  - Initiative sparked by close call with DNR wristband. Effort has implications for
      access.

PMID- 18092575
TI  - Honing your role as care coordination consultant. Get your voice heard.

PMID- 18092577
TI  - Psychotherapy as a rite of passage.
AB  - Some psychotherapies may work because they resemble rites of passage. To explore
      this idea, this article describes an "individual" case of depression in which
      drug, cognitive, and narrative approaches fell short of effectiveness, and change
      occurred in a series of experiences that resemble a rite of passage. This
      resemblance is illuminated by examining two apparently quite different healing
      processes--Alcoholics Anonymous and multifamily group therapy in schizophrenia-
      to explore the elements they have in common with the case described: the
      acceptance of what Victor Turner called a liminal experience, and the importance
      of witnesses to the ritual support for that acceptance. The discussion
      contributes to a loosening of the distinctions between the processes of
      individual, family, group, and other social therapies and leads to questions
      about the expert knowledge the therapist provides.

PMID- 18092578
TI  - The role of a mentoring group for family therapy trainees and therapists of
      color.
AB  - This article discusses the development, process, and impact of a mentoring group
      for family therapists of color. A within-group process for trainees of color in a
      predominantly White institution can provide a valuable resource for support,
      validation, empowerment, and collective action. The article examines how such
      mentoring promotes the effectiveness of therapists of color, as well as the
      practices and goals of social justice and diversity within training institutions
      and the field in general. Reflections and recommendations for implementing such a
      group are offered, as well as a personal narrative of a group member's experience
      of finding her voice in the group.

PMID- 18092579
TI  - Elder abuse and neglect in Latino families: an ecological and culturally relevant
      theoretical framework for clinical practice.
AB  - There is a scarcity of theoretical frameworks capable of describing precursors
      and dynamics associated with elder abuse and neglect in Latino families. The
      present manuscript seeks to address this gap in the literature by presenting an
      integrative theoretical framework that fosters an ecological and cultural
      understanding of elder abuse and neglect among Latinos. The proposed model rests
      on the premise that Latino families caring for elder adults have the ability to
      adapt to the demands of aging only if they are supported by nurturing
      environments. The usefulness of the model is threefold. First, the proposed model
      describes elder abuse and neglect as multifactorial phenomena and identifies
      specific risk factors associated with the etiology and maintenance of elder abuse
      and neglect in Latino families. Second, the model provides clinical applications,
      including reflections about the therapists' need to extend their scope of
      practice beyond traditional family therapy interventions. A brief case study is
      presented that illustrates the clinical application of the model with a Latino
      family. Implications for future research are discussed.

PMID- 18092580
TI  - Couple communication in stepfamilies.
AB  - Effective communication is assumed to help sustain couple relationships and is a
      key focus of most relationship education programs. We assessed couple problem
      solving communication in 65 stepfamily and 52 first-time-marrying couples, with
      each group stratified into high risk and low risk for relationship problems based
      on family-of-origin experiences. Relative to partners in first-time couples,
      partners in stepfamily couples were less positive, less negative, and more likely
      to withdraw from discussion. Risk was associated with communication in first-time
      but not stepfamily couples. Stepfamily couples do not exhibit the negative
      communication evident in high-risk first-time-marrying couples, and available
      relationship education programs that focus on reducing negative communication are
      unlikely to meet the needs of stepfamilies.

PMID- 18092581
TI  - Marital satisfaction and depression: a replication of the Marital Discord Model
      in a Latino sample.
AB  - The Marital Discord Model of Depression maintains that marital discord is an
      important antecedent in the development of depression. Although empirical
      evidence supports this premise, none of this research has been done with Latinos.
      The purpose of this study was to test the longitudinal relationship between
      marital satisfaction and depression among 99 Brazilian women. Using structural
      equation modeling, results indicated that marital satisfaction was a strong
      predictor of depression 2 years later. Marital satisfaction was also related to
      cooccurring depression. These results provide evidence that the Marital Discord
      Model of Depression is an appropriate theoretical model for the conceptualization
      of marital discord and depression with Latina women and suggest the potential
      utility of using couples therapy for treating depression among this population.

PMID- 18092582
TI  - An interpersonal perspective on depression: the role of marital adjustment,
      conflict communication, attributions, and attachment within a clinical sample.
AB  - Previous studies have focused on the difficulties in psychosocial functioning in
      depressed persons, underscoring the distress experienced by both spouses. We
      selected conflict communication, attribution, and attachment as important domains
      of depression in the context of marital adjustment, and we analyzed two
      hypotheses in one single study. First, we analyzed whether a clinical sample of
      couples with a depressed patient would differ significantly from a control group
      on these variables. Second, we explored to what degree these variables
      mediate/moderate the relationship between depressive symptoms and marital
      adjustment. The perspectives of both spouses were taken into account, as well as
      gender differences. In total, 69 clinical and 69 control couples were recruited,
      and a series of multivariate analyses of variance and regression analyses were
      conducted to test both hypotheses. Results indicated that both patients and their
      partners reported less marital adjustment associated with more negative
      perceptions on conflict communication, causal attributions, and insecure
      attachment. In addition, conflict communication and causal attributions were
      significant mediators of the association between depressive symptoms and marital
      adjustment for both depressed men and women, and causal attributions also
      moderated this link. Ambivalent attachment was a significant mediator only for
      the female identified patients. Several sex differences and clinical implications
      are discussed.

PMID- 18092583
TI  - "You" and "I," "us " and them: a systemic-discursive approach to the study of
      ethnic stereotypes in the context of British-Greek heterosexual couple
      relationships.
AB  - Systemic family therapy accounts of ethnic stereotypes in the context of
      ethnically mixed couple relationships have tended to focus on the interpersonal
      psychological realm of the couple relationship. Discourse analytic research, on
      the other hand, has highlighted the role of such stereotypes in the construction
      of national identity and has stressed the importance of a historical and
      ideological approach. In this article, we will present our attempt to develop a
      systemic-discursive approach to the study of stereotypes in the particular
      context of British-Greek heterosexual couple relationships by building on both
      fields.

PMID- 18092584
TI  - Links between parental psychological violence, other family disturbances, and
      children's adjustment.
AB  - In a sample of 143 parent-child dyads from two-parent and separated families,
      this investigation documented the links between parental psychological violence
      and separation or divorce, severity of parental conflict, triangulation of the
      child in this conflict, and polarized parent-child alliances. The unique and
      combined contributions of all these variables to children's behavior problems
      were also assessed. Participants were parents, mostly mothers, and their 10-12
      year-old child. They were recruited through schools, community organizations, and
      newspapers. Questionnaires were administered at home. Findings suggest that
      separated families undergo more relational disturbances than two-parent families
      (more severe conflicts, more triangulation, stronger parent-child alliances), but
      the amount of parental psychological violence was similar in both groups.
      Psychological violence was associated with the severity of parental conflict,
      especially in two-parent families. Triangulation of the child in parental
      conflict was another correlate of psychological violence. Once all variables were
      controlled for, psychological violence remained the only significant correlate of
      children's externalized behavior problems. These findings raise the importance of
      preventing psychological violence toward children, especially in families plagued
      with severe parental conflicts.

PMID- 18092585
TI  - Anxiety within families: interrelations, consistency, and change.
AB  - In a community sample of mothers (N = 763), each with a focal child aged 4.5
      years, anxiety levels were high. Only 54% of mothers had anxiety scores within
      the "normal" Hospital Anxiety and Depression Scale (HADS) range, compared with
      85% for depression. A subsample (N = 116) was selected for two-parent families,
      one to three children, and mothers spread over low, medium, and high anxiety
      levels. Mothers' anxiety was not significantly related to age, education, or work
      status, but rather to mothers' and fathers' independent ratings of marital
      satisfaction and family functioning, and to fathers' own anxiety and depression.
      Fathers' anxiety was related not to their own views of marital satisfaction and
      family functioning, but rather to mothers' views and to maternal anxiety.
      Assessments 8 years later--of anxiety, depression, and family functioning--showed
      high consistency over time, particularly maternal anxiety (r = .70) and paternal
      depression (r = .81). Although means did not change significantly over time for
      fathers, mothers' anxiety, depression, and perceptions of family functioning all
      improved (p < .001). For parents who were later to separate (compared with the
      others), initial family functioning, dyadic adjustment, and maternal anxiety were
      significantly "worse." The strongest predictor of later break-up was fathers'
      dyadic adjustment.

PMID- 18092586
TI  - Assessment of family functioning in Caucasian and Hispanic Americans:
      reliability, validity, and factor structure of the Family Assessment Device.
AB  - The purpose of this study was to examine the factor structure, reliability, and
      validity of the Family Assessment Device (FAD) among a national sample of
      Caucasian and Hispanic American families receiving public sector mental health
      services. A confirmatory factor analysis conducted to test model fit yielded
      equivocal findings. With few exceptions, indices of model fit, reliability, and
      validity were poorer for Hispanic Americans compared with Caucasian Americans.
      Contrary to our expectation, an exploratory factor analysis did not result in a
      better fitting model of family functioning. Without stronger evidence supporting
      a reformulation of the FAD, we recommend against such a course of action.
      Findings highlight the need for additional research on the role of culture in
      measurement of family functioning.

PMID- 18092587
TI  - Exact reduced-complexity maximum likelihood reconstruction of multiple 3-D
      objects from unlabeled unoriented 2-D projections and electron microscopy of
      viruses.
AB  - In cryo-electron microscopy, the data is comprised of noisy 2-D projection images
      of the 3-D electron scattering intensity of the object where the orientation of
      the projections is unknown. Often, the images show randomly selected objects from
      a mixture of different types of objects. Objects of different type may be
      unrelated, e.g., different species of virus, or related, e.g., different
      conformations of the same species of virus. Due to the low SNR and the 2-D nature
      of the data, it is challenging to determine the type of the object shown in an
      individual image. A statistical model and maximum likelihood estimator that
      computes simultaneous 3-D reconstruction and labels using an expectation
      maximization algorithm exists but requires extensive computation due to the
      numerical evaluation of 3-D or 5-D integrations of a square matrix of dimension
      equal to the number of degrees of freedom in the 3-D reconstruction. By
      exploiting the geometry of rotations in 3-D, the estimation problem can be
      transformed so that the inner-most numerical integral has a scalar rather than a
      matrix integrand. This leads to a dramatic reduction in computation, especially
      as the number of degrees of freedom in the 3-D reconstruction increases.
      Numerical examples of the 3-D reconstructions are provided based on synthetic and
      experimental images where the objects are small spherical viruses.

PMID- 18092588
TI  - Evaluation of optimization methods for nonrigid medical image registration using
      mutual information and B-splines.
AB  - A popular technique for nonrigid registration of medical images is based on the
      maximization of their mutual information, in combination with a deformation field
      parameterized by cubic B-splines. The coordinate mapping that relates the two
      images is found using an iterative optimization procedure. This work compares the
      performance of eight optimization methods: gradient descent (with two different
      step size selection algorithms), quasi-Newton, nonlinear conjugate gradient,
      Kiefer-Wolfowitz, simultaneous perturbation, Robbins-Monro, and evolution
      strategy. Special attention is paid to computation time reduction by using fewer
      voxels to calculate the cost function and its derivatives. The optimization
      methods are tested on manually deformed CT images of the heart, on follow-up CT
      chest scans, and on MR scans of the prostate acquired using a BFFE, T1, and T2
      protocol. Registration accuracy is assessed by computing the overlap of segmented
      edges. Precision and convergence properties are studied by comparing deformation
      fields. The results show that the Robbins-Monro method is the best choice in most
      applications. With this approach, the computation time per iteration can be
      lowered approximately 500 times without affecting the rate of convergence by
      using a small subset of the image, randomly selected in every iteration, to
      compute the derivative of the mutual information. From the other methods the
      quasi-Newton and the nonlinear conjugate gradient method achieve a slightly
      higher precision, at the price of larger computation times.

PMID- 18092589
TI  - Classifying CT image data into material fractions by a scale and rotation
      invariant edge model.
AB  - A fully automated method is presented to classify 3-D CT data into material
      fractions. An analytical scale-invariant description relating the data value to
      derivatives around Gaussian blurred step edges--arch model--is applied to
      uniquely combine robustness to noise, global signal fluctuations, anisotropic
      scale, noncubic voxels, and ease of use via a straightforward segmentation of 3-D
      CT images through material fractions. Projection of noisy data value and
      derivatives onto the arch yields a robust alternative to the standard computed
      Gaussian derivatives. This results in a superior precision of the method. The
      arch-model parameters are derived from a small, but over-determined, set of
      measurements (data values and derivatives) along a path following the gradient
      uphill and downhill starting at an edge voxel. The model is first used to
      identify the expected values of the two pure materials (named L and H) and
      thereby classify the boundary. Second, the model is used to approximate the
      underlying noise-free material fractions for each noisy measurement. An iso
      surface of constant material fraction accurately delineates the material boundary
      in the presence of noise and global signal fluctuations. This approach enables
      straightforward segmentation of 3-D CT images into objects of interest for
      computer-aided diagnosis and offers an easy tool for the design of otherwise
      complicated transfer functions in high-quality visualizations. The method is
      applied to segment a tooth volume for visualization and digital cleansing for
      virtual colonoscopy.

PMID- 18092590
TI  - Self organizing motor maps for color-mapped image re-indexing.
AB  - Palette re-ordering is an effective approach for improving the compression of
      color-indexed images. If the spatial distribution of the indexes in the image is
      smooth, greater compression ratios may be obtained. As is already known,
      obtaining an optimal re-indexing scheme is not a trivial task. In this paper, we
      provide a novel algorithm for palette re-ordering problem making use of a motor
      map neural network. Experimental results show the real effectiveness of the
      proposed method both in terms of compression ratio and zero-order entropy of
      local differences. Also, its computational complexity is competitive with
      previous works in the field.

PMID- 18092591
TI  - Region-based transform coding of multispectral images.
AB  - We propose a new efficient region-based scheme for the compression of
      multispectral remote-sensing images. The region-based description of an image
      comprises a segmentation map, which singles out the relevant regions and provides
      their main features, followed by the detailed (possibly lossless) description of
      each region. The map conveys information on the image structure and could even be
      the only item of interest for the user; moreover, it enables the user to perform
      a selective download of the regions of interest, or can be used for high-level
      data mining and retrieval applications. This approach, with the multiple pieces
      of information required, may seem inherently inefficient. The goal of this
      research is to show that, by carefully selecting the appropriate segmentation and
      coding tools, region-based compression of multispectral images can be also
      effective in a rate-distortion sense, thus providing an image description that is
      both insightful and efficient. To this end, we define a generic coding scheme,
      based on Bayesian image segmentation and on transform coding, where several key
      design choices, however, are left open for optimization, from the type of
      transform, to the rate allocation procedure, and so on. Then, through an
      extensive experimental phase on real-world multispectral images, we gain insight
      on such key choices, and finally single out an efficient and robust coding
      scheme, with Bayesian segmentation, class-adaptive Karhunen-Loeve spectral
      transform, and shape-adaptive wavelet spatial transform, which outperforms state
      of-the-art and carefully tuned conventional techniques, such as JPEG-2000
      multicomponent or SPIHT-based coders.

PMID- 18092592
TI  - New temporal filtering scheme to reduce delay in wavelet-based video coding.
AB  - Scalability is an important desirable property of video codecs. Wavelet-based
      motion-compensated temporal filtering provides the most powerful scheme for
      scalable video coding and provides high-compression efficiency that competes with
      the current state of art codecs. However, the delay introduced by the temporal
      filtering schemes is sometimes very high, which makes them unsuitable for many
      real-time applications. In this paper, ue propose a new temporal filter set to
      minimize delay in 3-D wavelet-based video coding. The new filter set gives a
      performance at par with existing longer filters. The length of the filter can
      vary from two to any number of frames depending on delay requirements. If the
      frames are processed as separate groups of frames (GOFs), the proposed filter set
      will not have any boundary effects at the GOF. Experimental results are presented
      and conclusions are drawn.

PMID- 18092593
TI  - Selective error detection for error-resilient wavelet-based image coding.
AB  - This paper introduces the concept of a similarity check function for error
      resilient multimedia data transmission. The proposed similarity check function
      provides information about the effects of corrupted data on the quality of the
      reconstructed image. The degree of data corruption is measured by the similarity
      check function at the receiver, without explicit knowledge of the original source
      data. The design of a perceptual similarity check function is presented for
      wavelet-based coders such as the JPEG2000 standard, and used with a proposed
      "progressive similarity-based ARQ" (ProS-ARQ) scheme to significantly decrease
      the retransmission rate of corrupted data while maintaining very good visual
      quality of images transmitted over noisy channels. Simulation results with
      JPEG2000-coded images transmitted over the Binary Symmetric Channel, show that
      the proposed ProS-ARQ scheme significantly reduces the number of retransmissions
      as compared to conventional ARQ-based schemes. The presented results also show
      that, for the same number of retransmitted data packets, the proposed ProS-ARQ
      scheme can achieve significantly higher PSNR and better visual quality as
      compared to the selective-repeat ARQ scheme.

PMID- 18092594
TI  - Volumetric attribute filtering and interactive visualization using the Max-Tree
      representation.
AB  - The Max-Tree designed for morphological attribute filtering in image processing,
      is a data structure in which the nodes represent connected components for all
      threshold levels in a data set. Attribute filters compute some attribute
      describing the shape or size of each connected component and then decide which
      components to keep or to discard. In this paper, we augment the basic Max-Tree
      data structure such that interactive volumetric filtering and visualization
      becomes possible. We introduce extensions that allow (1) direct, splatting-based,
      volume rendering; (2) representation of the Max-Tree on graphics hardware; and
      (3) fast active cell selection for isosurface generation. In all three cases, we
      can use the Max-Tree representation for visualization directly, without needing
      to reconstruct the volumetric data explicitly. We show that both filtering and
      visualization can be performed at interactive frame rates, ranging between 2.4
      and 32 frames per seconds. In contrast, a standard texture-based volume
      visualization method manages only between 0.5 and 1.8 frames per second. For
      isovalue browsing, the experimental results show that the performance is
      comparable to the performance of an interval tree, where our method has the
      advantage that both filter threshold browsing and isolevel browsing are fast. It
      is shown that the methods using graphics hardware can be extended to other
      connected filters.

PMID- 18092595
TI  - A fast image super-resolution algorithm using an adaptive Wiener filter.
AB  - A computationally simple super-resolution algorithm using a type of adaptive
      Wiener filter is proposed. The algorithm produces an improved resolution image
      from a sequence of low-resolution (LR) video frames with overlapping field of
      view. The algorithm uses subpixel registration to position each LR pixel value on
      a common spatial grid that is referenced to the average position of the input
      frames. The positions of the LR pixels are not quantized to a finite grid as with
      some previous techniques. The output high-resolution (HR) pixels are obtained
      using a weighted sum of LR pixels in a local moving window. Using a statistical
      model, the weights for each HR pixel are designed to minimize the mean squared
      error and they depend on the relative positions of the surrounding LR pixels.
      Thus, these weights adapt spatially and temporally to changing distributions of
      LR pixels due to varying motion. Both a global and spatially varying statistical
      model are considered here. Since the weights adapt with distribution of LR
      pixels, it is quite robust and will not become unstable when an unfavorable
      distribution of LR pixels is observed. For translational motion, the algorithm
      has a low computational complexity and may be readily suitable for real-time
      and/or near real-time processing applications. With other motion models, the
      computational complexity goes up significantly. However, regardless of the motion
      model, the algorithm lends itself to parallel implementation. The efficacy of the
      proposed algorithm is demonstrated here in a number of experimental results using
      simulated and real video sequences. A computational analysis is also presented.

PMID- 18092596
TI  - Minimax optimal level-set estimation.
AB  - This paper describes a new methodology and associated theoretical analysis for
      rapid and accurate extraction of level sets of a multivariate function from noisy
      data. The identification of the boundaries of such sets is an important
      theoretical problem with applications for digital elevation maps, medical
      imaging, and pattern recognition. This problem is significantly different from
      classical segmentation because level-set boundaries may not correspond to
      singularities or edges in the underlying function; as a result, segmentation
      methods which rely upon detecting boundaries would be potentially ineffective in
      this regime. This issue is addressed in this paper through a novel error metric
      sensitive to both the error in the location of the level-set estimate and the
      deviation of the function from the critical level. Hoeffding's inequality is used
      to derive a novel regularization term that is distinctly different from
      regularization methods used in conventional image denoising settings. Building
      upon this foundation, it is possible to derive error performance bounds for the
      proposed estimator and demonstrate that it exhibits near minimax optimal error
      decay rates for large classes of level-set problems. The proposed method
      automatically adapts to the spatially varying regularity of both the boundary of
      the level set and the underlying function.

PMID- 18092597
TI  - Majorization-minimization algorithms for wavelet-based image restoration.
AB  - Standard formulations of image/signal deconvolution under wavelet-based
      priors/regularizers lead to very high-dimensional optimization problems involving
      the following difficulties: the non-Gaussian (heavy-tailed) wavelet priors lead
      to objective functions which are nonquadratic, usually nondifferentiable, and
      sometimes even nonconvex; the presence of the convolution operator destroys the
      separability which underlies the simplicity of wavelet-based denoising. This
      paper presents a unified view of several recently proposed algorithms for
      handling this class of optimization problems, placing them in a common
      majorization-minimization (MM) framework. One of the classes of algorithms
      considered (when using quadratic bounds on nondifferentiable log-priors) shares
      the infamous "singularity issue" (SI) of "iteratively reweighted least squares"
      (IRLS) algorithms: the possibility of having to handle infinite weights, which
      may cause both numerical and convergence issues. In this paper, we prove several
      new results which strongly support the claim that the SI does not compromise the
      usefulness of this class of algorithms. Exploiting the unified MM perspective, we
      introduce a new algorithm, resulting from using l1 bounds for nonconvex
      regularizers; the experiments confirm the superior performance of this method,
      when compared to the one based on quadratic majorization. Finally, an
      experimental comparison of the several algorithms, reveals their relative merits
      for different standard types of scenarios.

PMID- 18092598
TI  - A new twIst: two-step iterative shrinkage/thresholding algorithms for image
      restoration.
AB  - Iterative shrinkage/thresholding (IST) algorithms have been recently proposed to
      handle a class of convex unconstrained optimization problems arising in image
      restoration and other linear inverse problems. This class of problems results
      from combining a linear observation model with a nonquadratic regularizer (e.g.,
      total variation or wavelet-based regularization). It happens that the convergence
      rate of these IST algorithms depends heavily on the linear observation operator,
      becoming very slow when this operator is ill-conditioned or ill-posed. In this
      paper, we introduce two-step IST (TwIST) algorithms, exhibiting much faster
      convergence rate than IST for ill-conditioned problems. For a vast class of
      nonquadratic convex regularizers (l(p) norms, some Besov norms, and total
      variation), we show that TwIST converges to a minimizer of the objective
      function, for a given range of values of its parameters. For noninvertible
      observation operators, we introduce a monotonic version of TwIST (MTwIST);
      although the convergence proof does not apply to this scenario, we give
      experimental evidence that MTwIST exhibits similar speed gains over IST. The
      effectiveness of the new methods are experimentally confirmed on problems of
      image deconvolution and of restoration with missing samples.

PMID- 18092600
TI  - Weighted averaging for denoising with overcomplete dictionaries.
AB  - We consider the scenario where additive, independent, and identically distributed
      (i.i.d) noise in an image is removed using an overcomplete set of linear
      transforms and thresholding. Rather than the standard approach, where one obtains
      the denoised signal by ad hoc averaging of the denoised estimates provided by
      denoising with each of the transforms, we formulate the optimal combination as a
      conditional linear estimation problem and solve it for optimal estimates. Our
      approach is independent of the utilized transforms and the thresholding scheme,
      and as we illustrate using oracle-based denoisers, it extends established work by
      exploiting a separate degree of freedom that is, in general, not reachable using
      previous techniques. Our derivation of the optimal estimates specifically relies
      on the assumption that the utilized transforms provide sparse decompositions. At
      the same time, our work is robust as it does not require any assumptions about
      image statistics beyond sparsity. Unlike existing work, which tries to devise
      ever more sophisticated transforms and thresholding algorithms to deal with the
      myriad types of image singularities, our work uses basic tools to obtain very
      high performance on singularities by taking better advantage of the sparsity that
      surrounds them. With well-established transforms, we obtain results that are
      competitive with state-of-the-art methods.

PMID- 18092599
TI  - Blind deconvolution of medical ultrasound images: a parametric inverse filtering
      approach.
AB  - The problem of reconstruction of ultrasound images by means of blind
      deconvolution has long been recognized as one of the central problems in medical
      ultrasound imaging. In this paper, this problem is addressed via proposing a
      blind deconvolution method which is innovative in several ways. In particular,
      the method is based on parametric inverse filtering, whose parameters are
      optimized using two-stage processing. At the first stage, some partial
      information on the point spread function is recovered. Subsequently, this
      information is used to explicitly constrain the spectral shape of the inverse
      filter. From this perspective, the proposed methodology can be viewed as a
      "hybridization" of two standard strategies in blind deconvolution, which are
      based on either concurrent or successive estimation of the point spread function
      and the image of interest. Moreover, evidence is provided that the "hybrid"
      approach can outperform the standard ones in a number of important practical
      cases. Additionally, the present study introduces a different approach to
      parameterizing the inverse filter. Specifically, we propose to model the inverse
      transfer function as a member of a principal shift-invariant subspace. It is
      shown that such a parameterization results in considerably more stable
      reconstructions as compared to standard parameterization methods. Finally, it is
      shown how the inverse filters designed in this way can be used to deconvolve the
      images in a nonblind manner so as to further improve their quality. The
      usefulness and practicability of all the introduced innovations are proven in a
      series of both in silico and in vivo experiments. Finally, it is shown that the
      proposed deconvolutioh algorithms are capable of improving the resolution of
      ultrasound images by factors of 2.24 or 6.52 (as judged by the autocorrelation
      criterion) depending on the type of regularization method used.

PMID- 18092601
TI  - Selecting salient frames for spatiotemporal video modeling and segmentation.
AB  - We propose a new statistical generative model for spatiotemporal video
      segmentation. The objective is to partition a video sequence into homogeneous
      segments that can be used as "building blocks" for semantic video segmentation.
      The baseline framework is a Gaussian mixture model (GMM)-based video modeling
      approach that involves a six-dimensional spatiotemporal feature space.
      Specifically, we introduce the concept of frame saliency to quantify the
      relevancy of a video frame to the GMM-based spatiotemporal video modeling. This
      helps us use a small set of salient frames to facilitate the model training by
      reducing data redundancy and irrelevance. A modified expectation maximization
      algorithm is developed for simultaneous GMM training and frame saliency
      estimation, and the frames with the highest saliency values are extracted to
      refine the GMM estimation for video segmentation. Moreover, it is interesting to
      find that frame saliency can imply some object behaviors. This makes the proposed
      method also applicable to other frame-related video analysis tasks, such as key
      frame extraction, video skimming, etc. Experiments on real videos demonstrate the
      effectiveness and efficiency of the proposed method.

PMID- 18092602
TI  - Entropy-controlled quadratic markov measure field models for efficient image
      segmentation.
AB  - We present a new Markov random field (MRF) based model for parametric image
      segmentation. Instead of directly computing a label map, our method computes the
      probability that the observed data at each pixel is generated by a particular
      intensity model. Prior information about segmentation smoothness and low entropy
      of the probability distribution maps is codified in the form of a MRF with
      quadratic potentials so that the optimal estimator is obtained by solving a
      quadratic cost function with linear constraints. Although, for segmentation
      purposes, the mode of the probability distribution at each pixel is naturally
      used as an optimal estimator, our method permits the use of other estimators,
      such as the mean or the median, which may be more appropriate for certain
      applications. Numerical experiments and comparisons with other published schemes
      are performed, using both synthetic images and real data of brain MRI for which
      expert hand-made segmentations are available. Finally, we show that the proposed
      methodology may be easily extended to other problems, such as stereo disparity
      estimation.

PMID- 18092603
TI  - Entropy-based distortion measure and bit allocation for wavelet image
      compression.

PMID- 18092605
TI  - Cost vs. price of the American dream.

PMID- 18092606
TI  - Distance education: can it go the distance?

PMID- 18092607
TI  - Global health care in the hands of nurses.

PMID- 18092608
TI  - From Oregon to Croatia: a journey to nursing. Interview by Anne Remington.

PMID- 18092609
TI  - Geriatric nursing: preparing for the baby boomer generation.

PMID- 18092610
TI  - Retiring into nursing.

PMID- 18092611
TI  - What Brandon can teach nurses about leadership.

PMID- 18092613
TI  - Did you get an 'A'?

PMID- 18092612
TI  - A swab of coffee.

PMID- 18092614
TI  - Physician executive compensation continues climb.

PMID- 18092615
TI  - Medical tourism--health care in the global economy.

PMID- 18092616
TI  - Galileo's blunders--lessons for physician executives.

PMID- 18092617
TI  - How to navigate health care information technology and electronic medical
      records.

PMID- 18092619
TI  - Fulfilling the promise of evidence-based medicine.

PMID- 18092618
TI  - Integrating dictation into electronic documentation: is it worth the effort?

PMID- 18092620
TI  - Are you a transformational leader?

PMID- 18092621
TI  - Route to the top: deans at North America's academic medical schools.

PMID- 18092623
TI  - Practicing what I preach.

PMID- 18092622
TI  - On the mark: forecast PCP practice growth with precision.

PMID- 18092625
TI  - Self-serving altruism: not an oxymoron.

PMID- 18092624
TI  - Being bold and brave--taking a strategic approach to changing your career.

PMID- 18092626
TI  - Going solo in a group--part 3.

PMID- 18092627
TI  - Career change for physicians: are you a candidate?

PMID- 18092628
TI  - Should we prescribe heroin? A current Scottish debate.
AB  - There have been recent calls from within both Scotland and England for the wider
      prescription of heroin to heroin addicts as a way of coping with our burgeoning
      drug problem and as a route to reducing drug related criminality. But how
      feasible is heroin prescribing in this context? This paper considers some of the
      existing research evidence relating to heroin prescribing and looks also at the
      ethics and practicalities of prescribing heroin to heroin addicts in Scotland. We
      conclude that whilst the evidence on the benefits of heroin prescribing is far
      from clear cut there is a case for mounting a Scottish trial of heroin
      prescribing. Such a trial would need to be tightly controlled and rigorously
      evaluated. It would need to show that heroin prescribing was associated not only
      with a comparable level of harm reduction, as methadone prescribing, but that it
      was also an effective route towards drug users' eventual recovery and drug
      cessation.

PMID- 18092629
TI  - Variations in all cause and cardiovascular mortality by country of birth in
      Scotland, 1997-2003.
AB  - BACKGROUND AND AIMS: Country of birth provides a proxy for ethnic group for
      recent migrants. Major differences in mortality by country of birth have been
      demonstrated in England and Wales, but similar published data for Scotland are
      lacking. We aimed to examine variations in mortality by country of birth for
      Scottish residents. METHODS: We calculated standardised mortality ratios by
      country of birth for Scottish residents aged 25 years and over between January
      1997 and March 2003. RESULTS AND CONCLUSION: Comparisons with England and Wales
      showed high all-cause, coronary heart disease (CHD) and stroke mortality among
      Scottish residents born in Scotland, Northern Ireland, the Republic of Ireland,
      India and Hong Kong. However, most country of birth groups had similar or lower
      mortality than the Scottish born. These are the first data on mortality by
      country of birth in Scotland and they demonstrate major variations. Comparisons
      within the Scottish population might be interpreted as reassuring, since they do
      not show the excesses in CHD mortality by country of birth reported in England
      and Wales. However, the use of England and Wales as a comparison group shows a
      substantial excess of CHD risk among South Asians in Scotland, comparable to that
      reported in England and Wales.

PMID- 18092630
TI  - Outcome of aggressive fibromatosis treated with radiation therapy.
AB  - INTRODUCTION: The purpose of this study is to report the clinical course and
      outcome in 7 patients with aggressive fibromatosis. MATERIAL AND METHODS: Between
      the years 2000 and 2003, 7 patients who were treated with combined modalities
      were evaluated retrospectively. Patients' demographic information, including age
      and gender, tumour characteristics, surgical resection, and the use of
      radiotherapy were recorded and evaluated. RESULTS: The mean patient age was 34
      years. The median time to follow-up was 15.5 months. Resection was performed with
      positive surgical margins in three cases. Three patients were evaluated as
      inoperable and one patient was treated with debulking surgery. All patients
      received radiation therapy with a median dose of 51 Gy. At follow-up, three
      patients had no evidence of disease, three patients were alive with disease, and
      one patient died 15 days after radiotherapy. CONCLUSION: Local control is the
      primary problem in aggressive fibromatosis. There is no appropriate treatment for
      aggressive fibromatosis and the type of treatment depends on tumour
      characteristics and location as well as patient characteristics.

PMID- 18092631
TI  - A survey of current surgical treatment of acute gallstone disease in the west of
      Scotland.
AB  - BACKGROUND: National guidelines exist for the treatment of acute gallstone
      pancreatitis, but not for the management of acute cholecystitis (AC). AIMS: To
      establish the preferred management of uncomplicated AC and adherence to
      guidelines for the management of mild gallstone pancreatitis in the west of
      Scotland. METHODS: A postal survey of all 100 consultant general surgeons in the
      west of Scotland. RESULTS: 67 of 71 responses received were suitable for
      analysis. For uncomplicated AC, 24 (36%) perform urgent laparoscopic
      cholecystectomy (LC), 16 (24%) perform same admission LC after clinical
      improvement. 23 (34%) perform interval LC after discharge. Within this group, 9
      surgeons (13%) manage AC conservatively due to insufficient operating time or
      equipment when on call. In mild gallstone pancreatitis, 33 (49%) perform same
      admission LC, 13 (19%) perform sphincterotomy, 3 (4.5%) perform one of these
      depending on the patient and 6 (9.5%) refer to a colleague with an interest in
      upper gastrointestinal surgery. CONCLUSIONS: The majority of surgeons (over 60%)
      manage AC with same admission LC. Of those who do not, more than a third report
      lack of resources as being the reason. The majority of surgeons in the West of
      Scotland manage mild gallstone pancreatitis in accordance with current
      guidelines.

PMID- 18092632
TI  - The changing face of infection: a comparative review of admissions to a regional
      infection unit over three decades.
AB  - BACKGROUND AND AIMS: Our group previously published retrospective analyses of 12
      months of admissions to the Grampian Regional Infectious Diseases Unit from 1980
      81 and from 1991. This study aimed to collect data in 2001 and to compare annual
      admission numbers, diagnoses, duration of stay and outcome in 1980-81, 1991 and
      2001. METHODS: Data on all admissions was collected prospectively throughout
      2001. This was compared with the previously published data. RESULTS: Total
      admissions rose from 605 in 1980-81 to 900 in 1991 and to 1152 in 2001. Sixty one
      percent of admissions in 1980-81 were confirmed as having infection compared to
      72% in 1991 and to 83% in 2001. The most common reason for admission in 2001 was
      skin and soft tissue infection, but this was only the ninth commonest reason in
      1981. Mean length of stay fell from 9.6 days in 1980-81 to 7.4 days in 1991 and
      to 5.5 days in 2001. The mortality rate fell from 3.1% in 1981 and 1991 to 1.0%
      in 2001. CONCLUSIONS: This study demonstrates significant changes in type, number
      and outcome of admissions to a regional infection unit. We discuss possible
      reasons for these changes.

PMID- 18092633
TI  - Childhood empyema in North-East Scotland over the past 15 years.
AB  - INTRODUCTION: The incidence of paediatric empyema is rising in the United Kingdom
      and North America. The reasons for increasing admissions are unclear. Management
      in tertiary units is often required. We report our experience in North-East
      Scotland over the last 15 years. METHODS: Empyema patients <15 yrs admitted to
      the Royal Aberdeen Children's Hospital between 1 st January 1990 and 1st June
      2006 were identified using discharge coding. Data was collated from case notes.
      Patient characteristics, microbiology results, hospital stay and management are
      studied. RESULTS: Twenty eight children (M:F = 1:1) were admitted. Mean age = 6.8
      yrs. Twenty seven out of twenty eight presented with localising respiratory
      symptoms or signs. In 12/28 an organism was isolated. Streptococcus pneumoniae
      was the commonest isolate, and where polymerase chain reaction (PCR) testing was
      employed, 3/3 cases were serotype 1. Fourteen out of twenty eight required
      surgery: open (8/14) or thoracoscopic (6/14) decortication. Two thoracoscopic
      cases proceded to open decortication. No complications were observed. Mean
      hospital stay = 11.4 days. Twelve were managed in high dependency unit (HDU) with
      a mean stay of 7.1 days. DISCUSSION: We demonstrate similar trends in North-East
      Scotland to those reported elsewhere. Serotype 1 streptococcus pneumoniae is the
      most isolated. Multi-drug resistance is not seen in our population. A
      surveillance programme is now established and reasons for the increasing
      incidence should become apparent.

PMID- 18092634
TI  - The early impact of the United Kingdom Chronic Kidney Disease (CKD) guidelines on
      the number of new attendances at renal clinics.
AB  - INTRODUCTION: In April 2006 the United Kingdom (UK) Chronic Kidney Disease (CKD)
      guidelines and laboratory estimated glomerular filtration rate (eGFR) reporting
      were introduced to encourage identification and appropriate management of
      patients with CKD. The aim of this study was to assess the early impact of the
      implementation of the UK CKD guidelines on new patient attendances at nephrology
      clinics in our unit. METHODS: The number of adult new patients, sex, mean age and
      number in each CKD stage were analysed in consecutive 6 month blocks from 2000 to
      2006. RESULTS: The number of new attendances gradually rose 2000 to 2006 until an
      abrupt 48% rise from 333 to 492 patients in the 6 months before and after June
      2006. Between the second 6 months of 2005 and second 6 months of 2006 the
      proportion of females (43.4% to 56.3%; p<0.0001) and mean age (61.3 v 66.4 years;
      p<0.0001) rose abruptly. The increase was mainly in patients with stage 3B (eGFR
      30-44.9ml/min/1.73m2) and stage 4 CKD (15-29.9ml/min/1.73m2). DISCUSSION: The
      data demonstrate that substantial changes in practice can be implemented rapidly
      within both primary and secondary care. Further studies will determine if this is
      going to improve outcome in patients with CKD.

PMID- 18092635
TI  - Ankylosing spondylitis.

PMID- 18092636
TI  - Hypertension.
AB  - Hypertension is a common condition affecting one in four adults. It is a leading
      cause of cardiovascular morbidity and mortality and appropriate treatment
      strategies that are both clinically and cost effective are key to the management
      of this condition. Recent guidelines have focused on addressing total
      cardiovascular risk and recommended rational combinations of antihypertensives as
      well as highlighting the importance of lifestyle intervention. Recent advances
      have increased understanding of the pathogenesis of hypertension and have opened
      the possibility of novel interventions for treatment.

PMID- 18092637
TI  - Sir William Macewen (1848-1924): surgeon and clinical photographer.
AB  - The eminent surgeon Sir William Macewen (1848-1924), kept a series of Private
      Journals (PJs) of cases he encountered on the surgical wards of the Glasgow Royal
      Infirmary (GRI). From 1881 photographs featured in the PJs, soon afterwards
      Macewen began to duplicate images and mount them on boards, which formed the
      basis of his teaching collection. When he moved to the University of Glasgow and
      the Western Infirmary, Glasgow (WI) in 1892 Macewen continued to expand his
      collection of clinical photographs.

PMID- 18092638
TI  - Retained intra-abdominal surgical instruments: time to use nascent technology?
AB  - Retention of surgical instruments is a possible complication of surgery;
      moreover, its occurrence has typically been used to denote poor surgical care on
      the part of the individual surgeon and the healthcare system. In the literature,
      it is not surprising that instances of retained foreign bodies are underreported
      to minimize exposure to possible litigation.

PMID- 18092639
TI  - Resection of benign duodenal neoplasms.
AB  - Primary small bowel neoplasms (PSBN) are uncommon, accounting for less than 15
      per cent of all gastrointestinal tumors. Benign duodenal neoplasms (BDN) are
      rare, comprising only 10 to 20 per cent of all PSBN. The treatment is generally
      surgical resection ranging from local excision to pancreaticoduodenectomy
      depending on size, location, and number of lesions. Patients undergoing surgical
      treatment for BDN at Vanderbilt University Medical Center from July 1984 to April
      2006, were identified and reviewed retrospectively. Medical records were examined
      for demographics, operative details, results, and complications. Twenty-six
      patients were identified of which 56 per cent were male and the mean age was 56
      +/- 14 years. Lesions were found throughout the duodenum, but the majority (62%)
      were ampullary. Nearly 75 per cent were adenomas, including over half with
      dysplasia. Operative interventions and complication rates were: duodenal
      resection with primary anastomosis (n=3, 0%), local excision (n=6, 50%),
      ampullary resection (n=10, 30%), and pancreaticoduodenectomy (n=7, 86%). There
      were no reoperations or mortalities. Mean followup was 14 months. BDN are an
      increasingly common problem in an era of frequent use of upper endoscopy. The
      surgical management of these lesions must be tailored to their size, number,
      location, and malignant potential. A wide variety of surgical procedures can be
      performed with acceptable morbidity.

PMID- 18092640
TI  - Developing a new bariatric surgery program.
AB  - We initiated a new bariatric surgery program in February 2004. Before starting
      the program, we initiated a systemic planning process to design, develop, and
      implement a comprehensive, multidisciplinary program. Between May 2004 and June
      2006, 178 patients underwent Roux-en-Y gastric bypass to treat morbid obesity at
      our institution. We have had no pulmonary emboli and no deaths. Twenty-one
      patients (11.8%) developed wound infection after surgery. Thirteen patients
      (7.3%) developed stenosis at the gastrojejunostomy. Five patients (2.8%) bled
      from the gastrojejunostomy. Four patients (2.2%) developed atelectasis. Three
      patients (1.6%) developed an internal hernia after surgery. One patient (0.5%)
      developed deep venous thrombosis. Two patients (1.1%) developed small bowel
      obstruction from adhesions. One patient developed a leak (0.6%). By 6 months
      after surgery, our patients have lost an average of 85 pounds (53% excess weight
      loss). By 12 months, they have lost an average of 104 pounds (65% excess weight
      loss). A focused effort to reduce infection has dropped our wound infection rate
      to 0 per cent in the past 6 months. Our results indicate that with proper
      planning, it is possible to initiate a new program and achieve excellent
      outcomes. Proper planning, systematic implementation, and a focus on patient
      education are critical to success.

PMID- 18092641
TI  - Approach to management of intussusception in adults: a new paradigm in the
      computed tomography era.
AB  - Intussusception has been considered an operative indication in adults as a result
      of the risk of ischemia and the possibility of a malignant lead point. Computed
      tomographic (CT) scans can reveal unsuspected intussusception. All CT reports
      from July 1999 to December 2005 were scanned electronically for letter strings to
      include the keyword intussusception. Identified CT scans were analyzed to
      characterize the intussusception and associated findings. Clinical, laboratory,
      pathological, and follow-up variables were gleaned from medical records. Findings
      were analyzed by treatment and findings at operation. Review of 380,999 CT
      reports yielded 170 (0.04%) adult patients (mean age, 41 years) with
      intussusceptions described as enteroenteric in 149 (87.6%), ileocecal in eight
      (4.7%), colocolonic in 10 (5.9%), and gastroenteric in three (1.8%). Radiological
      features included mean length of 4.4 cm (range, 0.8-20.5 cm) and diameter of 3.2
      cm (range, 1.6-11.5 cm). Twenty-nine (17.1%) had a lead point, and 12 (7.1%) had
      bowel obstruction. Clinically, 88 (48.2%) patients reported abdominal pain, 52
      (30.6%) had nausea and/or vomiting, and 74 (43.5%) had objective findings on
      abdominal examination. Thirty of 170 (17.6%) patients underwent operation, but
      only 15 (8.8%) patients had pathologic findings that correlated with CT findings.
      Seven had,enteroenteric intussusceptions from benign neoplasms (two), adhesions
      (one), local inflammation (one), previous anastomosis (one), Crohn's disease
      (one), and idiopathic (one). Three had ileocolic disease, including cecal cancer
      (one), metastatic melanoma (one) and idiopathic (one; whereas five patients had
      colocolonic intussusception from colon cancer (three), tubulovillous adenoma
      (one), and local inflammation (one). Of the 15 without intussusception at
      exploration, five had pathology related to trauma, four had nonincarcerated
      internal hernia after Roux-en-Y gastric bypass, four had negative explorations,
      one had adhesions, and one had appendicitis that did not correlate with CT
      findings. No patient in the observation group required subsequent operative
      exploration for intussusception at mean 14.1 months (range, 0.25-67.5 months)
      follow up. All operative patients demonstrated gastrointestinal symptoms versus
      55.3 per cent of the observation group (P < 0.006). Analysis of CT features
      demonstrated differences among patients observed without operation, those without
      intussusception at exploration, and confirmed intussusception with regard to mean
      intussusception length 3.8 versus 3.8 versus 9.6 cm, diameter 3.0 versus 3.2
      versus 4.8 cm, lead point 12.1 per cent versus 30 per cent versus 53.3 per cent,
      and proximal obstruction 3.8 per cent versus 0 per cent versus 46.7 per cent,
      respectively. Intussusceptions in adults discovered by CT scanning do not always
      mandate exploration. Most cases can be treated expectantly despite the presence
      of gastrointestinal symptoms. Close follow up is recommended with imaging and/or
      endoscopic surveillance. Length and diameter of the intussusception, presence of
      a lead point, or bowel obstruction on CT are predictive of findings that warrant
      exploration.

PMID- 18092642
TI  - Primitive stem cells residing in the skeletal muscle of adult pigs are mobilized
      into the peripheral blood after trauma.
AB  - This study was designed to determine if trauma causes the release of adult
      derived blastomere-like stem cells (BLSCs) from skeletal muscle into the
      circulating blood of adult pigs. Experimental procedures followed the guidelines
      of Fort Valley State University's Institutional Animal Care and Utilization
      Committee. Pigs were traumatized by splenectomy followed by pancreatectomy. Blood
      samples and skeletal muscle biopsies were taken before and after trauma. Adult
      derived BLSCs were isolated from skeletal muscle and blood samples following
      established procedures. Nontraumatized skeletal muscle contained approximately
      277 million BLSCs per gram of muscle. After trauma, skeletal muscle contained
      approximately 2 million BLSCs per gram of muscle. Blood taken before trauma
      contained approximately 22 million BLSCs per milliliter, whereas approximately
      512 million BLSCs per milliliter were present within the blood after trauma.
      Blood values were statistically significant with a P < 0.05. This report is the
      first demonstration that trauma causes the release of adult-derived BLSCs from
      skeletal muscle into blood. Further studies are required to elucidate the roles
      that adult-derived BLSCs play in the response to injury and in the healing
      process. Surgeons must take a role in this evolving field.

PMID- 18092643
TI  - Endovascular repair of ruptured abdominal aortic aneurysms: experience in a
      community hospital.
AB  - The endovascular technique has been recently used as an alternative procedure for
      selected patients with ruptured abdominal aortic aneurysm (RAAA) as a result of
      the potential for decreasing morbidity, mortality, and recovery time. We examined
      our institution's results with endovascular repair of RAAA. Between July 2005 and
      April 2006, four patients underwent endovascular repair of infrarenal RAAA. We
      performed a retrospective analysis of our comorbidities, operation time, length
      of intensive care unit and hospital stay, morbidity and mortality, blood
      transfusions, and secondary interventions on these patients at our institution.
      The median age was 73.2 years (range, 66-82 years); 75 per cent were male and 25
      per cent were female. Mean operating time was 90 minutes. We had no operative or
      postoperative mortalities. Five complications occurred in three patients. These
      included acute renal failure, common femoral artery intimal dissection, graft
      thrombosis of the iliac limb, ischemic colitis, and chronic obstructive pulmonary
      disease exacerbation. Endovascular repair of RAAA by an endovascular team is
      feasible in the community hospital setting. Our limited number of patients in
      this study does not allow us to compare it directly with results from the
      standard open procedure. A larger, multicenter study may eventually show this
      method to be helpful in patients who require repair of RAAA.

PMID- 18092644
TI  - Swallowing disorders in trauma patients: impact of tracheostomy.
AB  - Tracheostomy is associated with increased aspiration rates, and swallowing
      disorders have not been well-studied in trauma patients with tracheostomy.
      Swallowing evaluations were conducted in 224 patients (102 trauma and 122
      nontrauma patients). Half of the patients in each group had tracheostomies.
      Bedside swallow studies were conducted in 40 patients, videofluoroscopy swallow
      studies in 100 patients, and both studies in 84 patients. chi2, Fisher's exact
      test, Cramer's V, and descriptive statistics were used for data analysis.
      Aspiration occurred in 35 per cent (36 of 102) of trauma patients with or without
      tracheostomy and in 36 per cent (22 of 61) of nontrauma patients with
      tracheostomy. Aspiration with and without penetration was observed in 54 per cent
      of trauma patients (55% with tracheostomy) compared with 67 per cent of all
      nontrauma patients (61% with tracheostomy). Trauma patients with head injuries
      exhibited 41 per cent (26 of 63) aspiration and 68 per cent (43 of 63) dysphagia
      compared with 26 per cent (10 of 39) and 59 per cent (23 of 39) in trauma
      patients with other injuries. There was a lower incidence of dysphagia in trauma
      patients (65% versus 81% in nontrauma) and in patients with tracheostomy (71%
      versus 77% without tracheostomy). Tracheostomy was not associated with increased
      dysphagia or aspiration.

PMID- 18092645
TI  - Morbid obesity impacts mortality in blunt trauma.
AB  - Twenty-six per cent of adults in the Unites States are obese and trauma remains a
      major cause of death. We assessed the impact of morbid obesity on mortality in
      patients with blunt trauma. We reviewed the records of patients with a body mass
      index 40 kg/m2 or greater injured by blunt trauma from 1993 to 2003 and compared
      them with a 4:1 control population with a normal body mass index and matched for
      sex and constellation of injuries. For comparison, patients were categorized by
      Injury Severity Score 9 or less or Injury Severity Score 10 or greater. Student t
      test and chi2 were used for statistical analysis. P < 0.05 was considered
      significant. One hundred seven morbidly obese patients were identified and
      compared with 458 control subjects with a normal body mass index and matched for
      sex and constellation of injuries. Although the morbidly obese patients were
      found to be significantly younger, those who incurred multiorgan injury
      experienced a significantly longer hospital length of stay and displayed a
      greater than fourfold increase in mortality when compared with the control
      subjects. Furthermore, the number of morbidly obese patients admitted over the 10
      year period significantly increased by fourfold (0.4% to 1.5%). Over the last
      decade, there has been a significant increase in morbidly obese patients cared
      for in our trauma center. Although these patients were significantly younger with
      a similar Glasgow Coma Score as that of the control population, morbid obesity
      significantly increased mortality when the injury from blunt trauma transitioned
      from a single to a multiorgan injury.

PMID- 18092646
TI  - The effect of postoperative aspirin on random pattern flaps in rats.
AB  - Our laboratory has been studying the effect of aspirin, given alone or in
      combination with other medications, on random pattern skin flaps. We have
      consistently found that preoperative aspirin in high doses (200 mg/kg) increases
      flap survival, apparently as a result of its ability to modify the inflammatory
      reaction and/or direct vasodilatation, and not as a consequence of
      antiaggregation of platelets. In an effort to further elucidate how this effect
      is modulated, we designed this experiment in which we gave aspirin after the
      operative procedure to simulate an acute clinical surgical problem such as a
      failing or ischemic flap. Our results failed to show any difference between the
      rats that received postoperative aspirin and the untreated control group. It
      would appear that aspirin given postoperatively is not able to counteract the
      noxious elements that affect flap survival. This work indicates an important
      relationship between the timing of administration and the beneficial effects of
      aspirin. By investigating fully the mechanism whereby aspirin is able to improve
      flap survival, we hope to isolate this mechanism so an alternative
      pharmacological agent, safer than aspirin, can be found for clinical use.

PMID- 18092647
TI  - Surgisis mesh repair of a postsacrectomy perineal hernia along with posterior
      proctosigmoidectomy for concomitant stricture.
AB  - Postsacrectomy hernias are uncommon and can present with different signs and
      symptoms, including constipation, fecal incontinence, bowel obstruction, pain,
      and posterior bulging. We report a 50-year-old man who underwent sacrectomy for
      malignant fibrosarcoma complicated with sacral hernia. He presented with
      obstructive symptoms resulting from a strictured segment of herniated sigmoid
      colon and underwent bowel resection along with repair of his hernia. We
      additionally present a review of the literature and treatment of this rare
      disease.

PMID- 18092648
TI  - The abdominal cocoon: a rare cause of intestinal obstruction in two patients.
AB  - The abdominal cocoon is a rare disease that is characterized by total or partial
      encasement of the small bowel by a thick and fibrotic membrane. After an
      increased number of case reports, the characteristic age group and sex
      distribution of abdominal cocoon have changed. Although the etiology is unknown,
      congenital malformation is implicated as the causative factor in the two patients
      in this report. Although preoperative diagnosis is a matter of challenge and
      usually made at laparotomy, our experience suggests that computed tomographic
      evidence of clustered small bowel loops encased by a thin membrane-like sac is a
      characteristic preoperative finding in patients with abdominal cocoon. Surgical
      removal of the membrane and adhesions is the most appropriate choice of therapy.

PMID- 18092649
TI  - Ballistic arterial trauma to the lower extremity: recent South African
      experience.
AB  - The aim of this study was to determine the current outcome of gunshots to the
      arteries of the lower extremity. The authors conducted a retrospective analysis
      of 104 patients with gunshots to the femoral (n=71) and popliteal (n=33) artery.
      One hundred four patients presented over the 60-month period. Ninety-six (92%)
      were male and eight of 104 female. Ninety-nine were gunshot injuries, five from
      shotguns. Nine patients had injury to the common femoral artery, 62 patients had
      injury to the superficial femoral artery, and 33 had popliteal artery injury. One
      patient died in the emergency room and another died in the postoperative period,
      giving an overall in-hospital mortality of two of 104 (1.9%). Forty-three of 70
      femoral reconstructions had completion angiograms compared with 20 of 32
      popliteal artery reconstructions (P=1). Nineteen of 63 (30%) of the completion
      angiograms prompted revision of the reconstruction. Of the 63 patients who had
      completion angiograms, two of 63 (3%) required amputation. Seven of 39 (18%)
      patients who did not have completion angiograms required amputation (P = 0.025).
      Including the primary amputation, there were 10 amputations in the 103 patients
      (9.7%) who survived to undergo operation. Ballistic arterial trauma of the lower
      limb leads to significant disability. Completion arteriography leads to revision
      of the reconstruction in nearly one-third of instances and significantly reduces
      amputation rate.

PMID- 18092650
TI  - Fate of retained capsule: a pathognomonic for surgery.
AB  - Since its introduction in 2001, Wireless Video Capsule enteroscopy is gaining
      acceptance due to its high diagnostic potential and minimal risk. In some
      centers, it offers an alternative approach to visualize the small intestine and
      to evaluate patients with suspected small bowel disease. We present a series of
      known complications of this procedure and call for a more proactive role in the
      management of retained capsule.

PMID- 18092651
TI  - Foreign body ingestion and management: "I swallowed a crack pipe".
AB  - There is a wide variety of objects that find their way into the human
      gastrointestinal tract, either accidentally or deliberately. In this case a crack
      pipe was ingested in its entirety. Despite the seemingly rare and random nature
      that this scenario presents, this patient's care serves to reinforce what should
      be done to successfully manage a patient with an ingested foreign body, as well
      as the important issues related to crack cocaine abuse.

PMID- 18092652
TI  - Spontaneous hepatic hemorrhage in older women.
AB  - Spontaneous liver hemorrhage in older women is not well described. We report an
      experience with five postmenopausal women who spontaneously bled from the liver.
      All five patients presented with acute bleeding. Four were treated
      nonoperatively. No tumor was identified in any patient. Four patients acutely
      were discharged alive and well, but one died after operation to control bleeding.
      Spontaneous liver hemorrhage can occur in a variety of clinical settings, but an
      association with older women taking hormone replacement and anticoagulation has
      not been reported.

PMID- 18092653
TI  - Standardized uptake values for breast carcinomas assessed by fluorodeoxyglucose
      positron emission tomography correlate with prognostic factors.
AB  - Several studies have revealed the diagnostic value of fluorodeoxyglucose-positron
      emission tomography for breast carcinomas. However, breast carcinomas display
      considerable variation in 18F-labeled 2-fluoro-2-deoxy-D-glucose uptake, and few
      papers have reported the clinical utility of the standardized uptake values
      (SUV). The purpose of this study is to investigate the relationship between SUV
      assessed by positron emission tomography (PET) and the clinicopathological
      characteristics of breast carcinoma. We reviewed 52 breast carcinomas of 45
      patients presented at our department between January 2004 and July 2005. We
      compared the histopathological findings of the breast carcinomas with the
      preoperative SUV. Of the 52 breast carcinomas, 49 (94%) were detected by
      preoperative PET. A positive correlation was found between the SUV and tumor size
      (P < 0.01), histological grade (P < 0.01), the expression of the estrogen
      receptor (P < 0.001), progesterone receptor (P < 0.01), and p53 (P < 0.01). The
      number of metastatic axillary lymph nodes (r = 0.73; P < 0.0001) and the MIB-1
      labeling rates (r = 0.5; P < 0.01) correlated with the SUV of the breast
      carcinomal. No relationship existed between the SUV and the following:
      histological tumor types (P = 0.07), human epidermal growth factor receptor-2
      status (P = 0.10), and the presence of metastatic lymph nodes (P = 0.10). The SUV
      of the breast carcinomas correlate with several histopathological and
      immunohistochemical prognostic factors. We can obtain information on the degree
      of malignancy of the carcinoma and prognostic factors by preoperative PET
      examination.

PMID- 18092654
TI  - Pancreatic resection for metastatic renal cell carcinoma to the pancreas.
AB  - Although extremely rare, for most primary malignancies, the presence of
      metastases to the pancreas is a harbinger of diffuse systemic involvement. Clear
      cell renal cell carcinoma (RCC) of the kidney differs in that respect. Metastatic
      deposits tend to be isolated and diffuse systemic involvement may be absent. An
      Institutional Review Board-approved retrospective review of three cases of
      histologically confirmed RCC metastases to the pancreas was performed. We present
      their preoperative workup, surgical treatment, histopathological findings, and
      postoperative course. Three patients, all women, underwent distal pancreatectomy
      and splenectomy. Mean time period between nephrectomy and findings of pancreatic
      metastasis was 11.6 years. One patient had a major complication with a pancreatic
      fistula. Two patients have developed extrapancreatic recurrences. Resection of
      RCC metastases to the pancreas may offer a survival advantage in a select group
      of patients. Development of metastatic deposits after a prolonged disease-free
      period may actually be a negative prognostic indicator, implying a rapid and
      uncontrollable change in tumor biology.

PMID- 18092655
TI  - Can acute appendicitis be treated by antibiotics alone?
AB  - Emergency appendectomy at presentation has been the standard of care for acute
      appendicitis. We examined the use of antibiotics as an alternative treatment.
      From September 2002 to August 2003, 170 consecutive patients diagnosed with acute
      appendicitis without abscess were reviewed retrospectively. Patients were divided
      into two groups: Group I (n=151) underwent emergency appendectomy and Group II
      (n=19) received antibiotics alone. The mode of treatment was at the attending
      surgeon's discretion. The overall complication rate was eight per cent for Group
      I and 10 per cent for Group II patients (P = 0.22). Group II patients suffered no
      complications during antibiotic treatment, and any complications that did occur
      developed after subsequent appendectomy. One Group II patient had recurrent
      appendicitis (5%). The length of stay was 2.61 +/- 0.21 days for Group I and 2.95
      +/- 0.38 days for Group II patients (P = 0.57). Patients with acute appendicitis
      may be treated safely with antibiotics alone without emergency appendectomy.

PMID- 18092656
TI  - Perioperative myocardial infarction and risk of death with and without
      preoperative beta blockers.
AB  - This study compares patients who have had a myocardial infarction in the
      perioperative period who were on perioperative beta blockers with those who had a
      myocardial infarction and were not on perioperative beta blockers. The charts of
      68 patients were reviewed retrospectively. The timing and diagnosis of the
      myocardial infarction, gender, age, type of surgery, type of anesthesia,
      diabetics, preoperative medical clearance, and deaths were recorded. A subgroup
      of patients who had significant bleeding perioperatively or postoperatively were
      compared with patients with no bleeding problems. From 1998 through 2006, there
      were 46,003 patients who had surgery and 68 perioperative infarcts. Of the 68
      patients, 25 received perioperative beta blockers and 11 died. Of the 43 patients
      who did not receive beta blockers, 22 died. There was no statistically
      significant difference when the patients were analyzed for concomitant bleeding
      or nonbleeding with regards to survival and beta blockers.

PMID- 18092657
TI  - Jules Germain Cloquet (1790-1883)--drawing master and anatomist.
AB  - Jules Germain Cloquet, the famed French anatomist, surgeon, and professor, may
      not be remembered as one of the pioneers of hernia surgery; however, his
      contributions have provided surgeons with detailed anatomical descriptions that
      have been useful in developing innovative surgical techniques. Cloquet has many
      eponyms associated with him, including: Cloquet's fascia, Cloquet's gland or
      lymph node of Cloquet, Cloquet's hernia, Cloquet's ligament, Cloquet's canal, and
      Cloquet's septum. A man blessed with artistic talents, Cloquet was the author of
      many theses, as well as anatomical volumes that were comparable to the works of
      other great anatomists of his time. His first thesis, entitled Recherches
      Anatomiques sur les Hernies de l'Abdomen, described the locations where inguinal
      and crural herniae are more likely to occur in terms of the cremaster muscle, the
      peritoneum, and the spermatic vessels. Wax sculpture training required extensive
      knowledge in the natural sciences, anatomy, physiology, and pathology, as were
      acquired by Jules Cloquet as a pupil of Achille-Cleophas Flaubert, the father of
      the famous French novelist Gustave Flaubert (author of Madame Bovary). Cloquet
      attracted many pupils with his innovative teaching style and implementation of
      anatomical preparations, drawings, and sketches on the black board with chalk.
      The legacy of this famed individual lives on today in the anatomical structures
      described by Cloquet.

PMID- 18092658
TI  - Venous thromboembolism in trauma patients.
AB  - Serial venous duplex scans (VDS) were done in 507 trauma patients with at least
      one risk factor (RF) for venous thromboembolism (VTE) during a 2-year study
      period. Deep vein thrombosis (DVT) was detected in 31 (6.1%) patients. This
      incidence was 3.1 per cent in low (1-2 RFs), 3.4 per cent in moderate (3-5 RFs),
      and 7.7 per cent in high (> or =6 RFs) VTE scores (P = 0.172). Incidence was
      statistically different (3% vs. 7.2%, P = 0.048) on reanalyzing patients in two
      risk categories, low-risk (1-4 RFs) and high-risk (> or =5 RFs). Only 4 of 16 RFs
      had statistically higher incidence of DVT in patients with or without RFs:
      previous VTE (27.3% vs. 5.6%, odds ratio (OR) 6.628, P = 0.024), spinal cord
      injury (22.6% vs. 5%, OR 5.493, P = 0.001), pelvic fractures (11.4% vs. 5.1%, OR
      2.373, P = 0.042), and head injury with a greater than two Abbreviated Injury
      Score (10.5% vs. 4.2%, OR 2.639, P = 0.014). On reanalyzing patients with > or =5
      RFs vs. <5RFs, obesity (14.3 vs. 6.1%, P = 0.007), malignancy (5.6% vs. 0.6%, P =
      0.006), coagulopathy (10.8% vs. 1.8%, P = 0.000), and previous VTE (3.2% vs. 0%,
      P = 0.019) were significant on univariate analysis. Patients with DVT had 3.70 +/
      1.75 RFs and a 9.61 +/- 4.93 VTE score, whereas, patients without DVT had 2.66
      +/- 1.50 RFs and a 6.83 +/- 3.91 VTE score (P = 0.000). DVTs had a direct
      positive relationship with higher VTE scores, length of stay, and number of VDS
      (>1 r, P < or = 0.001). Increasing age was a weak risk factor (0.03 r, P = 0.5).
      First two VDS diagnosed 77 per cent of DVTs. Patients with injury severity score
      of > or =15 and 25 had higher DVTs compared with the ones with lower injury
      severity score levels (P < or = 0.05). Pulmonary embolism was silent in 63 per
      cent and DVTs were asymptomatic in 68 per cent.

PMID- 18092659
TI  - Small bowel adenocarcinoma complicating Crohn's disease: case series and review
      of the literature.
AB  - Colonic adenocarcinoma frequently complicates inflammatory bowel disease of the
      colon, but small bowel adenocarcinoma (SBA) is a rare complication of Crohn's
      disease (CD). We present two patients with SBA in CD and review the literature
      with regards to CD-related SBA. A 45-year-old male with a 17-year history of
      ileal CD presented with obstructive symptoms but no radiographic evidence of a
      mass. After laparoscopic ileocolectomy and repair of incidental ileosigmoid
      fistula, pathology showed a T3N0 adenocarcinoma within the ileal CD. Two years
      after his resection he was without evidence of disease. A 59-year-old male with a
      15-year history of CD presented with an acute exacerbation. Small bowel follow
      through demonstrated a long ileal stricture for which he underwent an ileocolic
      resection. Postoperative pathology confirmed a T3N1 CD-related SBA. He died from
      metastatic cancer 3 months later. Review of the literature identified 154 cases
      of SBA complicating CD with several distinguishing features from de novo SBA.
      Patients with SBA and CD are, as a group, younger and more likely to be male. SBA
      is rarely diagnosed preoperatively in these patients, and has a poor prognosis
      due to its advanced stage at diagnosis.

PMID- 18092660
TI  - Timing of laparoscopic cholecystectomy for acute cholecystitis: evidence to
      support a proposal for an early interval surgery.
AB  - We evaluated the safety and feasibility of delayed urgent laparoscopic
      cholecystectomy (LC) performed beyond 72 hours to overcome the logistical
      difficulties in performing early urgent LC within 72 hours of admission with
      acute cholecystitis (AC), and to avoid earlier readmission with recurrent AC in
      patients awaiting delayed interval. Patients admitted with AC were scheduled for
      urgent LC. Patients who underwent early urgent LC were compared with those who
      had delayed urgent surgery. Fifty consecutive patients underwent urgent LC for AC
      within 2 weeks of admission. There were no conversions and no bile duct injuries.
      Delayed surgery (n=36) neither prolonged operating time (90 vs. 85 minutes), nor
      increased operative morbidity (9.7% vs. 7.7%) or mortality (2.4% vs. 7.7%)
      compared with early surgery (n=14). Although delayed surgery was associated with
      shorter postoperative hospital stay (1 vs. 2 days, P = 0.029), it prolonged total
      hospital stay (9 vs. 5 days, P < 0.0001). Delay of LC beyond 72 hours neither
      increases operative difficulty nor prolongs recovery. It might be more cost
      effective to schedule patients who could not undergo early urgent LC but are
      responding to conservative treatment for an early interval LC within 2 weeks of
      presentation with AC.

PMID- 18092661
TI  - Anatomical basis of liver hanging maneuver: a clinical and anatomical in vivo
      study.
AB  - Liver Hanging Maneuver (LHM) provides better exposure of the deeper section plane
      together with Inferior Vena Cava (IVC) protection during right hepatectomies
      without primary liver mobilization. This study assessed the feasibility and
      complication rates of LHM focusing on the anatomical distribution of the
      accessory hepatic veins in the retrohepatic portion of the IVC. From January 2002
      to December 2005, LHM was planned in 49 consecutive major hepatectomies. The IVC
      retrohepatic portion was studied during the anhepatic phase in 17 liver
      transplantations with IVC preservation. The diameter and location of the vein
      openings were recorded after IVC division into nine portions. LHM was achieved in
      47/49 patients (96%). Bleeding occurred in only one patient (2%) and did not
      entail procedure interruption. The anatomical study revealed a total of 86 veins
      present in 17 cases (5.18 +/- 4 per patient) and classified them according to
      diameter (<3, 3 to 6, and >6 mm), as small (n=40), medium (n=29), and large
      (n=17), respectively. Nine openings were found in the avascular channel for 6/17
      (35%) patients (small n=6, medium n=3, large n=0). LHM is a highly feasible
      procedure with minor bleeding risks due to the lower density and small diameter
      of short hepatic veins and caudate veins present in the avascular channel.

PMID- 18092663
TI  - Internationally educated nurses.

PMID- 18092662
TI  - Regarding prophylactic inferior vena cava filter insertion for trauma: intensive
      care unit versus operating room.

PMID- 18092664
TI  - CARNA supports revisions to restricted activities for RNs.

PMID- 18092665
TI  - Nursing in the military breaking boundaries and forging ties.

PMID- 18092666
TI  - Ethical distress and values.

PMID- 18092667
TI  - Rural and urban caregivers for older adults in Poland: perceptions of positive
      and negative impact of caregiving.
AB  - This study examines rural-urban differences in informal caregivers' perceptions
      of caregiving. The study's theoretical framework is based on the two-factor model
      of caregiving, which views caregiving as having both positive and negative
      impact. Data were collected in personal interviews with 126 rural and 127 urban
      caregivers in the Bialystok region. The COPE-Index was used to assess caregivers.
      Rural caregivers reported a greater negative impact of caregiving than their
      urban counterparts, controlling for caregiver socio-demographic characteristics
      and care-recipient disability level. There was no difference in caregivers'
      perceptions of positive aspects of caregiving. These findings are consistent with
      previous research, which suggests that rural caregivers experience greater
      caregiver burden. Better understanding of rural-urban differences in caregiving
      outcomes can be useful in designing supportive services for informal caregivers
      in Poland.

PMID- 18092668
TI  - Image theory, goal incompatibility, and retirement intent.
AB  - Identity, as a guiding concept for work and retirement decisions, is explored in
      the current study. Image theory suggests that actions that "fit" with the goals
      of the trajectory image are fundamental for maintaining a positive and consistent
      self-identity (Beach, 1998; Beach & Mitchell, 1987). Incompatibility is the
      mechanism that evaluates whether retiring or continued work provides sufficient
      "fit" with the goals one hopes to achieve. In the current study, the "fit" of the
      trajectory image with retirement and work was measured in 238 full-time
      employees. Consistent with image theory predictions, individuals' perception of
      the incompatibility between five personal goals, within the trajectory image, and
      the choices of working and retiring predicted 25% of their retirement intent.
      Further support for goal incompatibility as a decision criterion is provided by
      findings showing it yielded better prediction than an alternative model based on
      goal facilitation, and equal prediction to an alternative model based on
      cost/benefit. Overall, the results are consistent with image theory and expand on
      continuity theory's (Atchley, 1999) concept of identity as fundamental for
      predicting retirement intent.

PMID- 18092669
TI  - Intergenerational triads in skipped-generation grandfamilies.
AB  - The past decades have seen growth in numbers of children raised by grandparents
      without their parent at home, called skipped-generation grand-families. This
      mixed methods study examined statements made by 459 grandmothers about core
      family relationships between grandmother and child, grandmother and parent, and
      parent and child. Families were grouped into intergenerational triad types based
      on patterns of closeness: all close relationships (triple-bonded), two close
      relationships (double-bonded), one close relationship (single-bonded), or weak
      relationships between all three family members (not-bonded). Well-being declined
      steadily for grandmothers from highest in triple-bonded, to lowest in not-bonded
      families, reflecting their high stake in all three core relationships. For
      grandchildren, well-being was low when the child failed to bond firmly to either
      grandmother or parent. On the other hand, children did well if they were close to
      their grandmother, even when substance abusing parents were emotionally isolated
      in the family, suggesting resilient children overcome parental neglect when
      provided with good grandparent care.

PMID- 18092670
TI  - Cognitive aging: activity patterns and maintenance intentions.
AB  - This study examined relationships between cognitive functioning in older people
      and (1) levels of mental, physical and social activities, and (2) intentions
      regarding maintenance of cognitive functioning. Participants (N=145) were 70-91
      years of age, varied in health status and socio-economic backgrounds. Current
      cognitive functioning was assessed by psychometric tests and real world problem
      solving tasks. Crystallized ability was indexed by the National Adult Reading
      Test (NART). Degree of involvement in mentally demanding activities was
      positively related to a fluid cognitive factor after effects of age, prior
      functioning, gender, health, and socio-economic status were accounted for. Social
      and physical activities were not related to the cognitive measures. Age effects
      on cognitive functioning were reduced among participants who reported undertaking
      activities intentionally to maintain cognitive functioning.

PMID- 18092671
TI  - A novel noninvasive technique for pulse-wave imaging and characterization of
      clinically-significant vascular mechanical properties in vivo.
AB  - The pulse-wave velocity (PWV) has been used as an indicator of vascular
      stiffness, which can be an early predictor of cardiovascular mortality. A
      noninvasive, easily applicable method for detecting the regional pulse wave (PW)
      may contribute as a future modality for risk assessment. The purpose of this
      study was to demonstrate the feasibility and reproducibility of PW imaging (PWI)
      during propagation along the abdominal aortic wall by acquiring
      electrocardiography-gated (ECG-gated) radiofrequency (rf) signals noninvasively.
      An abdominal aortic aneurysm (AAA) was induced using a CaCl2 model in order to
      investigate the utility of this novel method for detecting disease. The abdominal
      aortas of twelve normal and five CaCl2 mice were scanned at 30 MHz and
      electrocardiography (ECG) was acquired simultaneously. The radial wall velocities
      were mapped with 8000 frames/s. Propagation of the PW was demonstrated in a color
      coded cine-loop format all cases. In the normal mice, the wave propagated in
      linear fashion from a proximal to a distal region. However, in CaCl2 mice,
      multiple waves were initiated from several regions (i.e., most likely initiated
      from various calcified regions within the aortic wall). The regional PWV in
      normal aortas was 2.70 +/- 0.54 m/s (r2 = 0.85 +/- 0.06, n = 12), which was in
      agreement with previous reports using conventional techniques. Although there was
      no statistical difference in the regional PWV between the normal and CaCl2
      treated aortas (2.95 +/- 0.90 m/s (r2 = 0.51 +/- 0.22, n = 5)), the correlation
      coefficient was found to be significantly lower in the CaCl2-treated aortas (p <
      0.01). This state-of-the-art technique allows noninvasive mapping of vascular
      disease in vivo. In future clinical applications, it may contribute to the
      detection of early stages of cardiovascular disease, which may decrease mortality
      among high-risk patients.

PMID- 18092672
TI  - A three-dimensional registration method for microUS/ microPET multimodality small
      animal imaging.
AB  - Small-animal models are used extensively in disease research, genomics research,
      drug development and developmental biology. The development of noninvasive small
      animal imaging techniques with adequate spatial resolution and sensitivity is
      therefore of prime importance. In particular, multimodality small-animal imaging
      can provide complementary information. This paper presents a method for
      registering high-frequency ultrasonic (microUS) images with small-animal positron
      emission tomography (microPET) images. Registration is performed using six
      external multimodality markers, each being a glass bead with a diameter of 0.43
      0.60 mm, with 0.1 microl of [18F]FDG placed in each marker holder. A small-animal
      holder is used to transfer mice between the microPET and microUS systems.
      Multimodality imaging was performed on C57BL/6J black mice bearing WF-3 ovary
      cancer cells in the second week after tumor implantation and rigid-body image
      registration of the six markers was also performed. The average registration
      error was 0.31 mm when all six markers were used and increased as the number of
      markers decreased. After image registration, image segmentation and fusion are
      performed on the tumor. Our multimodality small-animal imaging method allows
      structural information from microUS to be combined with functional information
      from microPET, with the preliminary results showing it to be an effective tool
      for cancer research.

PMID- 18092673
TI  - Investigation of micro-ultrasound for microvessel imaging in a model of chronic
      total occlusion.
AB  - The aim of the current study is to investigate the ability of micro-ultrasound
      (microUS) to identify microvasculature in CTOs in vivo. Results are compared with
      MRI studies. CTOs were developed in nine porcine superficial femoral arteries
      (SFA) by percutaneous insertion of a dissolvable polymer plug. This model is
      characterized by acute thrombosis that later organizes into a fibrotic CTO
      containing abundant microchannels. 3D microUS images with Power Doppler (PD)
      overlays from the arteries were acquired at two timepoints: one and eight weeks
      after placement ofthe polymerplug. Phase contrast MRI and contrast enhanced MRI
      was also performed. Imaging was performed transcutaneously. Microvessels were
      identified in vivo in six of eight CTOs using microUS, and in three of seven CTO
      vessels with MRI, compared with five of seven seen histologically. PW Doppler
      profiles showed pulsatile blood velocities of approximately 2 cm/s. Intraluminal
      microvessels within CTOs can be consistently identified by 3D microUS. This
      technique appears to be more sensitive than MRI. MicroUS may play a role in
      guiding CTO interventions.

PMID- 18092674
TI  - Real-time three-dimensional transesophageal echocardiography for guiding
      interventional electrophysiology: feasibility study.
AB  - At present, there are limited methods of acquiring three-dimensional
      visualization of cardiac structure and function in real-time during
      interventional electrophysiology procedures. Images acquired for integration of
      computerized tomography and magnetic resonance imaging with electroanatomic
      mapping systems are static and are obtained earlier in time. The purpose of this
      study was to test the feasibility of real-time three-dimensional transesophageal
      echocardiography for the guidance of interventional electrophysiological studies.
      A matrix array transducer with 504 channels operating at 5 MHz in a 1 cm diameter
      steerable esophageal probe was used in conjunction with a scanner capable of real
      time 3D scanning of pyramidal volumes from 65 degrees to 120 degrees at rates up
      to 30 volumes per second. This device has a spatial resolution of approximately 3
      mm at 5 cm depth. The authors acquired real-time three-dimensional images of
      anatomic landmarks of value for electrophysiological procedures in five closed
      chest canines. Real-time, three-dimensional ultrasound imaging was also used for
      visualization and guidance of interventional catheter devices within the canine
      heart. Real-time three-dimensional images of the atria, pulmonary veins, and
      coronary sinus were acquired. Real-time 3-D color flow Doppler was employed to
      confirm patency. Multiple image planes of image volumes and rendered views were
      used to track catheter position and orientation. Images of left veno-atrial
      junctions have been confirmed by dissection. This study has demonstrated the
      feasiblity of using real-time three-dimensional transesophageal echocardiography
      for guiding interventional electrophysiology. The technology has the potential to
      fill a niche as an adjunct modality for cost-effective real-time interventional
      guidance and assessment, providing catheter and pacing lead visualization
      simultaneously with functional volumetric cardiac imaging.

PMID- 18092675
TI  - Ultrasound probe with integrated ECG lead: feasibility study.
AB  - We integrated electrocardiogram (ECG) leads onto the face of a cardiac ultrasound
      transducer and the exterior chassis of a simulated small, portable scanner to
      minimize the number of devices needed to collect cardiac information. Since the
      ECG leads were not placed on their standard locations, a precordial ECG was
      recorded.

PMID- 18092676
TI  - [An epidemiological study of rabies virus in domestic dogs, cats and wildlife and
      the immunogenicity study for rabies vaccines derived from different cell cultured
      virus strains].
AB  - For epidemiological investigation of the rabies virus carrier rates of domestic
      dogs, cats and wild animals like rodent animals and bats,three kinds of regions
      where rabies had higher incidence (Hunan and Guizhou Provinces), lower incidence
      (Jiangsu Province, Wuhan City) and provisionally rabies-free (Shenyang City) were
      selected. Then the antigenic types, the genovariation of the isolaled viruses and
      the currently vaccine matching of the virus strains were analyzed. The results
      showed that in China the principal host of rabies is dog,the total virus carrier
      rate of the captured dogs was 2.56%, and the highest positive isolation rate was
      20.0% in some monitoring site. However,there was no evidence about the rabies
      virus carrier rate in rodent animals,bats or other wild animals. The rabies
      vaccines which prepared from aG and CTN strains have already been produced
      successfully in China. The research showed that the nucleotide sequences of the
      newly isolated viruses were more similar with the glycoprotein gene of CTN
      strain. In order to evaluate the safety and the efficacy of the vaccines
      currently used, two groups (50 people each) were injected with vaccine of aG
      strain and CTN strain respectively in five surveillance points. The neutralizing
      antibody tested were 0.49 IU/mL-0.52 IU/mL and 6.7 IU/mL-7.53 IU/mL after the 7
      and the 14 days of vaccine injection respectively. In addition, the rates of
      antibody positive seroconversion were 45.1%-47.9% and 100% respectively, and
      there was no moderate or severe adverse reactions observed. These data showed the
      vaccines have satisfactory effect on safety and protection.

PMID- 18092677
TI  - [Identification of a functional ITAM-like sequence within G1 cytoplasmic tail of
      Hantaan virus].
AB  - The G1 cytoplasmic tail of Hantaan virus (HTNV) harbors a highly conserved
      region, which is homologous to immunoreceptor tyrosine-based activation motifs
      (ITAM) and is termed the ITAM-like sequence. To demonstrate the potential signal
      transducing activity of G1 ITAM-like sequence resembling the canonical ITAM
      within immune and endothelial cells, a series of experiments were performed to
      define its interaction with cellular kinases. The synthesized G1 ITAM-like
      peptide was shown to coprecipitate with cellular phosphoprotein complexes by an
      immune-complex kinase assay. Mutational analyses showed that this ITAM-like
      sequence was a substrate for the Src family kinase Fyn, and two conserved
      tyrosine residues were required for coprecipitating Lyn, Syk, and ZAP-70 kinases.
      These findings demonstrated that HTNV envelope glycoprotein G1 contains a
      functional ITAM-like sequence in its cytoplasmic tail, which can bind critical
      cellular kinases that regulate immune and endothelial cell functions.

PMID- 18092678
TI  - [The firstly confirmed pregnant woman case of avian influenza A (H5N1) by
      etiological research in China].
AB  - To investigate the cause of death of a pregnant woman with undefined pneumonia
      reported from the People's Hospital of Tongling City in Anhui Province on
      November 8, 2005, the patient's tracheal aspirates and serum samples were
      collected and tested by RT-PCR and Real-time PCR to detect viral nucleic acids of
      HA of A/H5N1, A/H7N7, A/H9N1 and A/M. Tracheal aspirates were inoculated into
      special pathogen free (SPF) embryonated eggs for cultivation and identification
      of virus. The HA gene of the virus was sequenced and analyzed. Serum samples were
      tested by HI assay to detect antibody of H5N1. The results showed that HA gene of
      A/H5N1 virus and A/M were positive in tracheal aspirates by both PCR tests. The
      serum sample collected on Nov. 9 was A/M gene positive by Real-time PCR. The
      analysis of HA gene of A/AnHui/1/2005 sequence showed that the receptor
      specificity and the connecting peptide between HA1 and HA2 were still avian
      influenza origin. The HI antibody of H5N1 was negative at 7th, 8th, 9th d of
      disease onset. This undefined pneumonia case was confirmed as the first pregnant
      woman case of avian influenza (H5N1) virus infection by etiology in the mainland
      of China.

PMID- 18092679
TI  - [Laboratory diagnosis and molecular characterization of highly pathogenic avian
      influenza virus (H5N1) in human in Hunan Province in 2005-2006].
AB  - To determine the etiologic agents of two atypical pneumonia human cases in Hunan
      Province in 2005-2006 and to study their pathogenic potential, the patients'
      respiratory tract samples and sera were collected. The respiratory tract samples
      were tested by real-time RT-PCR and RT-PCR methods, and the sera by
      hemagglutination-inhibition assay. Virus was isolated from case 2 and its genome
      was sequenced and analyzed. Results showed the H5 nucleic acid tests of two cases
      were positive. The H5-specific antibody titer of the convalescence serum of case
      1 showed a 4-fold greater rise than that of the acute phase. And case 2's
      antibody titer of acute phase was negative. The two atypical pneumonia cases were
      confirmed as the avian influenza A (H5N1) infection cases. Viral strain
      A/Hunan/1/2006 was isolated from case 2. Phylogenetic and molecular analysis
      suggested that 8 gene segments of A/Hunan/1/2006 originated from avian viruses.
      And A/Hunan/1/2006 was similar with viruses isolated from avian in Hunan
      Province. The isolated virus did not recombine with human influenza viruses and
      no obvious variation was observed.

PMID- 18092680
TI  - [Development and application of a safe SARS-CoV neutralization assay based on
      lentiviral vectors pseudotyped with SARS-CoV spike protein].
AB  - The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike
      protein (S) is a major target for neutralizing antibody. To develop and apply a
      safe neutralization assay for SARS-CoV, lentiviral SARS-CoV S pseudotypes had
      been constructed based on a three plasmid system, which contained pVRC8304
      (harboring codon optimized full-length SARS-CoV S protein), pCMV delta 8. 2 (HIV
      1 gag/pol construct) and pHR'CMV EGFP (the green fluorescent protein reporter
      construct). The pseudo-typed lentiviral particles were used to develop an in
      vitro microneutralization assay that was both sensitive and specific for SARS-CoV
      neutralizing antibody. We used this assay to determine the titers of the
      neutralizing antibodies (Nabs) in serum samples from mice immunized with various
      rVVs expressing different S fragments of SARS-CoV. The serum antibodies derived
      from S and various segments of S1 region neutralized SARS-CoV in vitro. No cross
      neutralization occurred with the goat antiserum prepared with inactivated HCoV
      OC43 or HCoV-229E. Neutralization titers measured by this assay were highly
      parallel with those measured by the assay using live SARS-CoV. Because the
      pseudotype assay does not require handling live SARS virus, it is a useful tool
      to determine serum neutralizing titers during natural infection and the
      preclinical evaluation of candidate vaccines.

PMID- 18092681
TI  - [Genome cloning and phylogenetic analysis of human bocavirus capsid gene].
AB  - The full-length genome of one human bocavirus (HBoV) and the VP1 sequences of
      nine HBoV were amplified from patients' samples by PCR, cloned into pGEM-T vector
      separately, and sequenced. In this study, the one full length gemome and nine VP1
      sequences of HBoV were aligened with 14 sequences of Parvoviruses which were
      canonical exemplars in Parvovirinae. Phylogenetic analysis showed that HBoV
      capsid sequences positioned closely to B19 parvovirus, although they positioned
      far in phylogenetic tree based on full length genome. Many similarities were
      found between HBoV and B19 in capsid by alignment on secondary structural
      elements. Because both B19 and HBoV are the only Parvoviruses that infect
      mankind, so study on HBoV may be used for reference to B19 which had been studied
      for about 30 years. By analysis of mutational sites, HBoV capsid protein showed a
      highly conserved secondary structural elements, but highly active in VP1-U,
      leading end of VP2 and insertions between the strands of the betaG-H. This cued
      that HBoV inclined to immune evasion and infectant adaptive faculty.

PMID- 18092682
TI  - [The molecular differences between genotype 1 and genotype 4 of HEV in their
      neutralization region].
AB  - HEV is classified into H (human) group and Z (zoonosis) group according to its
      compatible host. H group contains genotype 1 and genotype 2 HEV isolates which
      infect human only; Z group contains genotype 3 and genotype 4 HEV isolates which
      infect both human and animals. After analysis of amino acid sequences between
      ORF2 aa368 and aa606, four group-conserved sites that were all located in the
      neutralization region of ORF2 were identified. They are aa483, aa492, aa497 and
      aa599. Mutation analysis and capture PCR were then performed on these sites with
      a group of monoclonal antibodies. Results showed that the difference of the aa497
      between H and Z groups was responsible for the maintenance of their group
      specific immunodominant epitopes, probably through confirmation-dependent epitope
      changes. Thus, aa497 and its related change on the surface structure of HEV may
      play important roles in host selection by H and Z groups of HEV.

PMID- 18092683
TI  - [Sequence analysis and prokaryotic expression of nucleocapsid protein genes of
      human respiratory syncytial viruses isolated from children in Beijing].
AB  - :To characterize nucleocapsid (N) protein genes of human respiratory syncytial
      viruses isolated from children in Beijing and express the N genes in E.
      coli,seven HRSV strains (three subtype A and four subtype B) were isolated from
      clinical samples of infants and children with acute respiratory infections and
      visited the Children's Hospital affiliated to Capital Institute of Pediatrics in
      Beijing during the period of Jan. 2006 to Mar. Full length of N genes from seven
      HRSV strains were amplified by reverse-transcription PCR (RT-PCR). The seven PCR
      amplicons were sequenced after cloning into pUCm-T and the sequences were
      compared with the N genes from HRSVs in GenBank. N gene was amplified from
      recombinant plasmid pUCm-N9968 by PCR and then sub-cloned into the prokaryotic
      expression vector pET30a(+) after digestion with EcoR I and Xho I . The pET30a
      N9968 was transformed into E. coli BL21 (DE3) and expressed by inducing with
      IPTG. Target protein was characterized by SDS-PAGE electrophoresis and Western
      blot. The amplified N genes were 1 176 bp in length and the deduced N proteins
      were 391 amino acids in length. The nucleotide identities of N genes among these
      seven strains were 85.4%-99.7% and the de-duced amino acid similarities were
      95.4%-100%. The recombinant plasmid pET30a-N9968 had correct open reading frame
      confirmed by dual-enzyme digestion and sequence analysis. The fusion protein 6 x
      HisN was produced after inducing by 1 mmol/L IPTG at 37 degrees C. A unique
      protein band with molecular weight 49 kD was characterized by SDS-PAGE and
      purified by Ni2+ affinity chromatography column. Most of the target protein
      existed in inclusion body. Western blot analysis showed that the target protein
      had specific binding reaction to specific monoclonal antibody and human sera,
      indicating that the expressed protein is of specific antigenicity.

PMID- 18092684
TI  - [HPV DNA vaccines expressing recombinant CRT/HPV6bE7 fusion protein inhibit tumor
      growth and angiogenic activity].
AB  - This paper was to study the angiogenic inhibitory effect and the potential
      antitumor effect of the constructed recombinant DNA vaccine CRT/HPV6bE7 in vivo.
      The C57BL/6 mice were vaccinated respectively with recombinant CRT/HPV6bE7 DNA
      plamids. The inhibitory effects on angiogenesis of generated vaccines in vivo
      were evaluated by a bFGF-induced angiogenesis assay using the Matrigel kit. To
      investigate the potential antitumor effect, the mean tumor weights, sizes and
      tumor appearing times were measured in C57BL/6 mice treated with HPV6bE7
      expressing B16 cells. The results indicated that the recombinants CRT180/HPV6bE7
      and CRT180 showed strong anti-angiogenic effects in bFGF-induced angiogenesis in
      vivo. Moreover, CRT180/HPV6bE7 and CRT180 DNA vaccines could significantly
      inhibit the tumor growth in tumor challenge experiment, and CRT180/HPV6bE7 was
      superior to other vaccines in delaying tumor formation time, limiting tumor size
      and weight in tumor protection experiment. In conclusion, recombinant
      CRT180/HPV6bE7 DNA could elicit a most efficient anti-angiogenic effect and
      inhibit tumor growth in mice inoculated with DNA vaccines. The antiangiogenic
      activity of CRT were suggested residing in a domain between CRT 120-180 aa.

PMID- 18092685
TI  - [Generation of cell culture high-yield recombinant H3N2 subtype swine influenza
      vaccine candidate by reverse genetics].
AB  - High-yield H3N2 subtype swine influenza virus for large-scale vaccine production
      in cell culture was generated by reverse genetics. The rescued H3N2 (rH3N2)
      candidate virus contained hemagglutinin (HA) and neuraminidase (NA) genes derived
      from a field isolate A/Swine/Henan/S4/01 (H3N2), PB2 gene from A/PR/8/34, and the
      other five internal genes from A/Goose/Dalian/3/01 (H9N2). The rH3N2 virus titer
      in MDCK cell culture were measured by hemagglutination assay and the maximum
      virus titre of 1:512 hemagglutination unit was obtained after infection of MDCK
      cell for 60 h. The results of the present study indicated that rH3N2 virus was
      suitable for growth in MDCK cell culture and is feasible to be used for the
      production of cell grown influenza vaccine.

PMID- 18092686
TI  - [Study on the histopathology of cats inoculated with H5N1 subtype high pathogenic
      avian influenza virus originated from tigers].
AB  - In this study, the HPAIV A/Tiger/Harbin/01/2002 (H5N1) used was originated from
      tigers and propagated in SPF embryonated hen eggs. TCID5, of the virus was 10(
      7.36)/0. 05mL on MDCK cell. The cats were inoculated through bronchus route and
      then, the cats of dead and control were collected for histopathological and
      immunohistochemistry examination. Meanwhile, the emulsion supernatant fluid of
      organs and the pharyngeal swab samples of the dead cats were collected for RT
      PCR, survived cats and the control cats were tested for the presence of HI
      antibody by standard method. The results indicated that the damage of lungs from
      the dead cats were most obvious, the wide range of red consolidation focus
      emerged on the lobus pulmonis, the fused focus of infection caused injury of
      lungs. Histology under the microscope revealed diffuse alveolar damage,
      confluence phlegmasia pathology, infiltration of lymphomonocytes, sackful of
      infiltration of macrophages and manipulus protein-like effusion in the alveolar.
      By immunohistochemistry, the positively stained virus particles were found on the
      epithelial cells of bronchus and alveolus, and also in the endochylema of
      lymphomonocytes. The specific electophoretic band of 464bp amplified by RT-PCR
      from samples of pharyngeal swabs, lungs, kidneys, hearts and brains was as same
      as the theory value. HI antibody titers of the survived cat were 1:32.

PMID- 18092687
TI  - [Construction of rabbit hemorrhagic disease virus replicons and its replication
      in RK-13 cells].
AB  - To provide an efficient and safe technology platform for studying the replication
      and pathogenesis mechanisms of RHDV, the interaction between the RHDV and its
      host cells, a replicon system of RHDV, was constructed based on the infectious
      cDNA clone of RHDV, in which VP60 gene encoding the capsid protein was deleted,
      but all the necessary protease coding regions and non-coding regions were
      retained. Results from RT-PCR, IFA and qRT-PCR confirmed that the replicon RNA
      could efficiently replicate in RK-13 cells. Besides, the results also suggested
      that the capsid protein which is the structural protein of RHDV is necessary for
      maintaining the viral infectivity.

PMID- 18092688
TI  - [The analysis of bro genes of GD isolate of Bombyx mori nucleopolyhedrovirus].
AB  - BmNPV GD isolate from China was plaque-purified and four bro genes were cloned
      termed as bro-a,b,c,d. The obtained sequences were aligned to the related
      sequences in GenBank and the BmNPV CQ1 isolate preserved in our laboratory.
      Compared with genome sequences of BmNPV T3 isolate, bro genes of GD isolate
      housed insertion and deletion, and the changes of amino acid mainly occured at
      the N terminal of corresponding protein. The phylogenetic analysis of bro genes
      indicated that GD bro-d gene belongs to subgroup A together with T3, CQ1 bro-d
      and SC7 bro- III; GD bro-a, c genes belong to subgroup B together with T3, CQ1
      bro-a, c and SC7 bro-II; GD bro-b gene belongs to subgroup C together with T3,
      CQ1 bro-b, e and SC7 bro-I. The evolutionary relationship of bro genes showed
      vague relevance to their geographical location. The distribution character of bro
      genes in four BmNPV isolates is coincidence with the KANG's theory that the bro-d
      plays an irreplaceable functional role(s) during viral replication, while bro-a
      and bro-c functionally complement each other. Meanwhile, we postulate that 3 bro
      genes in SC7 isolate is probable the most simple form of bro genes.

PMID- 18092689
TI  - [Comparison of variable region genes of shrimp White Spot Syndrome Virus (WSSV)
      in different areas in China].
AB  - According to the conservative sequence in the epitaxial variable region of
      Thailand strain of WSSV published in GenBank,a pair of primers were designed to
      amplify the variable region genes of 5 local WSSV strains (ZHSH, ZHJ, HN, QD1,
      QD2) by PCR and then cloned. In accordance with the CN, the results indicated
      that the number of nucleotide of 5 strains were deleted more than 591bp of the TW
      and TH strains. The ZHSH and HN strains that deleted 591bp at the 3' end, and 454
      bp at the 5' end of variable gene was highly homologous with CN strain about
      99.3%. 229bp of ZHJ strain at the 5' end was homologous with CN about 99.3%, and
      deleted of 816bp at the 3' end. 97bp at the 5' end and 171bp at the 3' end of QD1
      and QD2 strains were homologous with CN strain about 99.3%, and about 777bp were
      absent in the middle. The above data showed that the variable region genes of
      WSSV had mutated more in China. The variable region gene of QD2 strain was
      coincidence with that of QD1 after propagating 10 generations in crayfish. The
      results indicated that the crayfish inoculation did not result in mutation of
      variable region genes of WSSV.

PMID- 18092690
TI  - [Integrin alphavbeta3 and virus infection].

PMID- 18092691
TI  - [Acute phase response following total hip replacement and in patients with
      aseptic loosening].
AB  - INTRODUCTION: Aseptic loosening is a result of the chronic inflammatory reaction
      in periprosthetic tissues. Its intensity depends on the implants construction
      material and reactivity of the host's tissues. The aim of the study was the
      evaluation of the acute phase proteins in various periods following total hip
      replacement and comparison between acute phase response observed in patients with
      well-functioning implants and with aseptic loosening. MATERIAL: The study group
      consisted of 97 patients following THR due to the hip osteoarthritis. Patients of
      Group I were evaluated before the surgery and 6 months after primary THR. Group
      II consisted of patients 3-4 years after primary THR. Group consisted of patients
      with aseptic loosening. Patients of all groups were divided according to the
      implant type (cemente/uncemented). METHODS: Concentrations of evaluated acute
      phase proteins: C-reactive protein (CRP), transferrin (Tf) and alpha-glycoprotein
      were assessed using immunoelectrophoresis. RESULTS: In vast majority of patients
      (71-95%) following THR had present w3 variant of AGP which should be negative in
      physiological conditions. The average concentrations of AGP and AGP-RC were
      higher in patients following cemented THR. CONCLUSIONS: Implantation of the
      endoprosthesis raises a chronic inflammatory reaction expressed by changes in the
      profiles of acute phase proteins. This process is more visible in patients
      following cemented THR. The profiles of the acute phase proteins in patients with
      aseptic loosening were not different than those observed in patients with well
      functioning implants, what makes them useless as a diagnostic tool for loosening.
      This lack of differences may be caused by adaptation of the generalised response
      to long lasting process of aseptic loosening

PMID- 18092692
TI  - [First experiences with total hip resurfacing arthroplasty].
AB  - MATERIAL: From may 2005 25 surface arthroplasties were made in 10 women and 15
      men in the age from 23 to 64 years (average 43 years). The main reason for
      arthroplasty was idiopathic arthritis in 20 patients. 24 ReCap (Biomet)
      endoprosthesis were implanted. The dysplastic BHR (Smith & Nephew) acetabular
      component was implanted in one patient because of the deficit of dysplastic
      acetabulum. RESULTS: The follow up is from 10 to 20 months (average 11 months).
      Clinical results in Harris Hip Score is from 90 to 100 points (average 95.8 pts).
      The average acetabular cup's angle of inclination is 51.2 degrees (from 40 to 77
      degrees), and average femoral heads angle is 140.3 degrees (from 131 to 148
      degrees). There were not any significant intraoperative and early postoperative
      complications. CONCLUSIONS: Early clinical results and data from bibliography
      confirm the value of surface arthroplasty in the treatment of young and active
      patients. The procedure is technically demanding.

PMID- 18092693
TI  - [Total hip replacement in young patients with use of MAYO prosthesis--early
      result of treatment].
AB  - Authors presented the results of the treatment of osteoarthritis of the hip with
      MAYO endoprosthesis. The paper is focused on young adults. 34 operations in the
      2000-2006 were performed. Cementless MAYO stems were used. 32 patients (24
      females and 8 males) were evaluated. The age of patients was 20-54 years (average
      32,7 years). The main cause of the hip osteoarthritis was DDH (50%). Among others
      we identified posttraumatic deformities (14.7%), avascular necrosis of the head,
      multiepiphyseal dysplasia and the other (35.3%). Cementless press-fit Trilogy cup
      (Zimmer) was applied in 94.1% and cementless threaded acetabular cup in 5.9%
      patients. Results were analyzed according to clinical Hip Harris score and
      radiological assessment. After 7 years follow up good and very good outcomes were
      found in the majority of patients. Mayo stem causes minor damage of
      intertrochanteric region during procedure and has minimal effect on medullary
      cavity. It is an advantage in a case of the migration of endoprosthesis. It
      preserves the bone stock and allows Total Hip Replacement with cementless stem.
      Obtained results confirm the value of implantation of this kind of endoprosthesis
      in the case of young adults. Longer follow up period and bigger group of patients
      are required to confirm our observations.

PMID- 18092694
TI  - [Modern opinions on treatment of the compressive neuropathies of the radial
      nerve].
AB  - In this article authors show actual opinions on two frequent compressive
      syndromes of the radial nerve: posterior interosseus nerve syndrome and radial
      tunnel syndrome. Different views on pathomechanism, methods of diagnostics and
      actual treatment standards are shown in this paper.

PMID- 18092695
TI  - [A comparison of the results of the conservative vs operative by percutaneous
      Kirschner-wiring treatment of fractures of the distal radius].
AB  - The objective of this study was comparing the results of the conservative (close
      reduction and immobilisation in the plaster splint) vs operative (percutaneous
      Kirschner-wiring) treatment of fractures of the distal radius. Sixty patients, 49
      women (82%) and 11 men (18%), who sustained an isolated, displaced fractures were
      randomly allocated to operative (30 patients) or conservative (30 patients)
      treatment. All patients were followed up at 1.5, 3 and finally at 6 months after
      fracture. The following variables were analysed: rate of secondary displacement,
      wrist range of motion, fingers loss of flexion, total grip strength, dorsal or
      volar tilt, radial angulation and radial length on the X-ray. Function of the
      hand was assessed with DASH questionnaire, cold sensitivity with McCabe scale and
      final outcome in Gartland-Werley and Castaing complex scales. The rate of
      secondary displacement was considered a primary outcome measure. RESULTS:
      Secondary displacement was noted in 8 patients (27%) treated conservatively, of
      whom 7 required surgery and those were withdrawn from the trial. Three fractures
      (10%) treated operatively displaced secondarily, but none required additional
      operation and all completed the follow-up. The rate of secondary displacement was
      statistically significantly (chi2 test, p < 0.05) more frequent in conservatively
      treated group. With regard to other analysed parameters, the statistically
      significant differences was found in total grip strength at 3 and 6 months
      assessments, and in DASH score at 6 months assessment, both favouring operative
      method. The remaining variables did not differ significantly between the groups
      treated conservatively and operatively. CONCLUSION: Our results have
      demonstrated, that percutaneous Kirschner-wiring of fractures of the distal
      radius is superior to the conservative treatment, because statistically
      significantly reduces the risk of secondary displacement and allows to obtain a
      stronger grip and better hand function within 6 months after fracture.

PMID- 18092696
TI  - [Treatment of physeal fractures in children].
AB  - The aim of the study was to determine final clinical and radiological results of
      epiphyseal fractures treated in our hospital. Thirty-five patients were included
      in the study (6 girls and 29 boys) aged from 5 to 17 years (mean 12.1 years).
      Follow up ranged from 2 to 20 years. According to Salter and Harris
      classification system 15 patients had type I and 20 had type II fracture.
      According to the Neer-Horowitz classification system of the proximal end of
      humerus one patient had grade III and three had grade IV fracture. Physeal
      fractures included: proximal end of humerus (n = 4), distal end of radius (n =
      16) (with coexistent distal end of ulna fractures in 6 cases), distal end of
      femur (n = 4), distal end of tibia (n = 3) and distal end fibula (n = 8). Six
      patients were treated with open reduction and K-wire fixation, three with
      skeletal traction and cast, one with closed reduction and K-wire fixation and
      twenty five with closed reduction and cast. Neurovascular deficit was noted in
      any of our patients at admission and after reduction. During follow-up we did not
      notice physeal arrest, changes in limbs axis or limb shortening in any of our
      patients. All our patients had good clinical results. In 2 cases in early
      postoperative follow-up limitation of shoulder abduction after physeal fracture
      of proximal humerus was observed. Restoration of proper anatomical conditions is
      conducive to restore function of growth plate. Kirschner wire fixation did not
      increase the risk of growth arrest. Physeal injuries at the end of growth did not
      cause limb axis changes.

PMID- 18092697
TI  - [Early clinical and radiological results following cervical disc arthroplasty].
AB  - The aim of this study was to assess early results of anterior cervical
      decompression and arthroplasty for cervical disc disease. The results of
      operations of 32 patients (43 instrumented levels) were examined to assess
      clinical outcome, the restoration of disc height, postoperative lordosis,
      mobility of instrumented segment and complication rate. Clinical outcome
      evaluated with VAS score improved from 7.5 preoperatively to 2.7 post operation.
      There was improvement in disc height measured by Tureyen method of 48%, 5 degree
      restoration of lordosis per segment and average 5 degree mobility of operated
      segment. In two cases spontaneous fusion occurred. There were no loosening of
      prosthesis observed. Overall the study shows that early results of arthroplasty
      are clinically efficient and safe as fusion. Assessment of biomechanical
      advantages of arthroplasty demands further observation to compare if long-term
      results are superior to fusion.

PMID- 18092698
TI  - [Avulsion fractures of tibial tuberosity in adolescents].
AB  - In this paper data on nine tibial tuberosity fractures were presented according
      to all types in Watson-Jones classification and one fracture of type IV according
      to Curtis. Two more fractures were presented that fulfilled clinical and
      radiological standards of the knee's extensory structures injury, but were not
      tibial tuberosity fractures. In operative treatment screws were used as well as
      Kirschner wires or both these devices together. The fracture's influence on knee
      motion and activity of proximal tibial growth cartilage were examined. All
      patients got back into full activity as before the fracture and except one case,
      there was no fracture's influence on proximal tibial growth cartilage found. In
      successful treatment achieving of the fracture's healing in best anatomical
      position and early physiotherapy are essential.

PMID- 18092699
TI  - [Transfer of the distal phalange of the ring finger as a method of reconstruction
      of the partially amputated thumb--preliminary report].
AB  - Loss of a thumb accounts for 60% decrease of functional value of the hand, thus
      any attempt of it's reconstruction is a priority in the field of hand surgery.
      Optimal reconstructive solution for subtotal thumb amputations has not been
      settled. The results of partial pollicization of ring finger in 5 adult men is
      presented. Four patients sustained distal subtotal thumb amputation (MCP joint
      level), one total amputation. In three patients the distal phalange of the ring
      finger was transferred with the DIP joint, FDP tendon and a fragment of extensor
      tendon. An effective movement of a newly created thumb's IP joint was achieved in
      two patients. In one patient with a total thumb amputation the transfer was
      followed by a pollicization of the second metacarpal with remnants of proximal
      phalange. The postoperative course was uneventful in all of the patients. The
      sensitivity tested on the pulp of the transferred finger equalized to the
      preoperative value, the hand strength was not diminished. The cosmetic result was
      excellent.

PMID- 18092700
TI  - [Modified algorithm in treatment of patients with chronic low back pain with
      neuroradiological diagnostic techniques].
AB  - The most difficult in proper qualification of the patient with chronic low back
      pain for an operative treatment is determination of the chance for satisfactory
      result. The diversity of the pain eliciting structure in the spine influence the
      decision. In the paper we have analyzed patient where the operative treatment was
      considered. In 149 patients divided in two groups the (not being previously
      operated on the spine--group 1 and after spine surgery--group 2) the
      neuroradiological procedures were performed (sacral epidural block, facet
      injections, root injections of the lumbar spine). As the result of this procedure
      in 108 patients (72%) surgical intervention at that time was abandoned.
      Conclusion. In our opinion the neuroradiological diagnostic procedures should be
      mandatory in back pain management of the patient were operative treatment is
      considered. We present the modified algorithm in diagnostic procedure preceding
      the operation.

PMID- 18092701
TI  - [Dupuytren's contracture limited to the distal interphalangeal joint--a case
      report].
AB  - A case of Dupuytren's contracture involving only the distal interphalangeal joint
      of the right little finger is reported. The contracture developed gradually
      during 6 months, after a minor trauma of this finger. Distal phalanx was fixed in
      60 degrees flexion in the distal and 30 degrees flexion in the proximal
      interphalangeal joints, but it did not disturbed patient's normal daily activity.
      Proximal interphalangeal flexion was easy reducible, but distal phalanx was
      settled in fixed flexion deformity. No pathology was seen in the palmar aspect of
      the midhand. At the exploration, a thickened 1 cm long cord localised at the
      radial side of the distal interphalangeal joint and extending across this joint
      was identified, and excised. This resulted in full correction of the flexion
      deformity. Histopathological examination revealed excised cord to be a fibrous
      tissue, typical for the Dupuytren's contracture.

PMID- 18092702
TI  - Patellar height after barrel-vault high tibial osteotomy.
AB  - The purpose of the study was to assess the influence of barrel-vault high tibial
      osteotomy on patellar position and to evaluate the reliability and interobserver
      variability of three patellar height ratios. The radiographs of 24 knees that had
      undergone barrel-vault height tibial osteotomy with available preoperative as
      well as postoperative radiographs of the last follow-up were enrolled in the
      study. The patellar position was evaluated with the use of the Insall-Salvati,
      Blackbourne-Peel and Caton-Linclau methods. The indices were calculated with the
      tibial slope angle measured by the Moore-Harvey method. The average patellar
      index in the Blackburne-Peel and Caton-Linclau measurements had a statistically
      significant tendency to increase after barrel-vault tibial osteotomy. The results
      of the Insall-Salvati assessment method showed no statistically significant
      differences. Intrasession ICCs (intraclass correlation coefficient) varied
      between 0.8 and 0.99. The kappa value for the inter-observer agreement of all
      three ratios determined varied between 0.48 for the Blackburne-Peel index and 0.5
      for the Insall-Salvati and Caton-Linclau indices. The average tibial slope before
      the surgery was 11.8 degrees (+/- 3.6) and decreased to 6.6 degrees (+/- 4.3). No
      significant associations between the index change and tibial slope change were
      detected. The data suggest that since some of patellar height indices measure
      different anatomical relationships, comparable types of indices should be used in
      order to estimate the patellar height or patellar relation to the joint line.

PMID- 18092703
TI  - Case report: amelanotic melanoma located on the lower extremity.

PMID- 18092704
TI  - Clinical diagnosis and evaluation of sinusitis in adults.

PMID- 18092705
TI  - Aspirin combined with clopidogrel (Plavix) decreases cardiovascular events in
      patients with acute coronary syndrome.

PMID- 18092706
TI  - Diagnosis and treatment of otitis media.
AB  - Diagnostic criteria for acute otitis media include rapid onset of symptoms,
      middle ear effusion, and signs and symptoms of middle ear inflammation.
      Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are
      the most common bacterial isolates from the middle ear fluid of children with
      acute otitis media. Fever, otalgia, headache, irritability, cough, rhinitis,
      listlessness, anorexia, vomiting, diarrhea, and pulling at the ears are common,
      but nonspecific symptoms. Detection of middle ear effusion by pneumatic otoscopy
      is key in establishing the diagnosis. Observation is an acceptable option in
      healthy children with mild symptoms. Antibiotics are recommended in all children
      younger than six months, in those between six months and two years if the
      diagnosis is certain, and in children with severe infection. High-dosage
      amoxicillin (80 to 90 mg per kg per day) is recommended as first-line therapy.
      Macrolide antibiotics, clindamycin, and cephalosporins are alternatives in
      penicillin-sensitive children and in those with resistant infections. Patients
      who do not respond to treatment should be reassessed. Hearing and language
      testing is recommended in children with suspected hearing loss or persistent
      effusion for at least three months, and in those with developmental problems.

PMID- 18092707
TI  - Ear infections in children: what you should know.

PMID- 18092708
TI  - The physical therapy prescription.
AB  - Numerous guidelines recommend physical therapy for the management of
      musculoskeletal conditions. However, specific recommendations are lacking
      concerning which exercises and adjunct modalities to use. Physical therapists use
      various techniques to reduce pain and improve mobility and flexibility. There is
      some evidence that specific exercises performed with the instruction of physical
      therapists improve outcomes in patients with low back pain. For most modalities,
      evidence of effectiveness is variable and controlled trials are lacking. Multiple
      modalities may be used to treat one clinical condition; decisions for the
      treatment of an individual patient depend on the expertise of the therapist, the
      equipment available, and the desire of the attending physician. A physical
      therapy prescription should include the diagnosis; type, frequency, and duration
      of the prescribed therapy; goals of therapy; and safety precautions.

PMID- 18092709
TI  - Evaluation of back pain in children and adolescents.
AB  - Back pain is fairly prevalent in healthy children and adolescents. When children
      or adolescents seek medical care for back pain, it is highly likely that
      underlying pathology will be identified. Common causes of back pain include
      nonspecific pain or muscle strain, herniated disk, spondylolysis, scoliosis, and
      Scheuermann's kyphosis. Less common causes include tumor, infection, and sickle
      cell crisis. If nonspecific back pain is suspected, treatment may include home
      based exercise, physical therapy, or nonsteroidal anti-inflammatory drugs. If the
      history and physical examination suggest underlying pathology, radiography,
      complete blood count, erythrocyte sedimentation rate, and a C-reactive protein
      measurement should be performed. Follow-up magnetic resonance imaging, computed
      tomography, or bone scanning may be needed depending on the suspected cause. It
      is generally accepted that the following factors warrant immediate evaluation:
      patient age younger than four years, persistent symptoms, self-imposed activity
      limitations, systemic symptoms, increasing discomfort, persistent night-time
      pain, and neurologic symptoms.

PMID- 18092711
TI  - Chronic pancreatitis: what you should know.

PMID- 18092710
TI  - Chronic pancreatitis.
AB  - Chronic pancreatitis is the progressive and permanent destruction of the pancreas
      resulting in exocrine and endocrine insufficiency and, often, chronic disabling
      pain. The etiology is multifactorial. Alcoholism plays a significant role in
      adults, whereas genetic and structural defects predominate in children. The
      average age at diagnosis is 35 to 55 years. Morbidity and mortality are secondary
      to chronic pain and complications (e.g., diabetes, pancreatic cancer). Contrast
      enhanced computed tomography is the radiographic test of choice for diagnosis,
      with ductal calcifications being pathognomonic. Newer modalities, such as
      endoscopic ultrasonography and magnetic resonance cholangiopancreatography,
      provide diagnostic results similar to those of endoscopic retrograde
      cholangiopancreatography. Management begins with lifestyle modifications (e.g.,
      cessation of alcohol and tobacco use) and dietary changes followed by analgesics
      and pancreatic enzyme supplementation. Before proceeding with endoscopic or
      surgical interventions, physicians and patients should weigh the risks and
      benefits of each procedure. Therapeutic endoscopy is indicated for symptomatic or
      complicated pseudocyst, biliary obstruction, and decompression of pancreatic
      duct. Surgical procedures include decompression for large duct disease
      (pancreatic duct dilatation of 7 mm or more) and resection for small duct
      disease. Lateral pancreaticojejunostomy is the most commonly performed surgery in
      patients with large duct disease. Pancreatoduodenectomy is indicated for the
      treatment of chronic pancreatitis with pancreatic head enlargement. Patients with
      chronic pancreatitis are at increased risk of pancreatic neoplasm; regular
      surveillance is sometimes advocated, but formal guidelines and evidence of
      clinical benefit are lacking.

PMID- 18092712
TI  - FPIN's clinical inquiries. Group medical visits for the management of chronic
      pain.

PMID- 18092713
TI  - Erythematous annular lesions.

PMID- 18092714
TI  - [Creutzfeldt-Jakob disease: what's new?].

PMID- 18092715
TI  - [Fibrous dysplasia of bone].
AB  - Fibrous dysplasia of bone is a congenital non hereditary benign bone disease,
      where normal bone is replaced by a fibrous-like tissue with immature
      osteogenesis. Prevalence is difficult to estimate, due to frequent asymptomatic
      lesions. Bone lesions are mono- or polyostotic and may be associated with bone
      pain and fragility, leading to fractures. In some patients or bone sites, they
      are hypertrophic, responsible for neurological complications. Imaging and, when
      necessary, histology are the cornerstones of the diagnosis. A common molecular
      defect, i.e. activating mutations of the GNAS gene, encoding the a subunit of the
      Gs protein in target cells, is responsible for bone cell alterations as well as
      for the involvement of other cells/tissues bearing the same molecular defect
      (melanocytes, endocrine cells). These mutations affect only somatic cells and are
      therefore not hereditary: antenatal diagnosis is not appropriate for this disease
      and genetic counselling is not very useful, except for reassuring the patients.
      The conventional therapeutic approach is essentially symptomatic (pain killers)
      and orthopaedic (prevention and treatment of bone complications). Recent
      publications have focused attention on pamidronate, which rapidly relieves bone
      pain in most patients, and progressively increases bone mineralization in
      osteolytic areas in about half of the patients. Tubular phosphate wasting is
      common and should be treated with phosphate supplement and calcitriol. The
      prognosis should improve with therapeutic advances, but this remains to be
      properly evaluated.

PMID- 18092716
TI  - [Craniopharyngioma].

PMID- 18092717
TI  - [Acute respiratory tract infections in children. I. Upper infections].

PMID- 18092718
TI  - [Epidemiology of acute upper and lower respiratory tract infections in children].
AB  - More than 200 antigenically distinct viruses have been documented as causes of
      sporadic or epidemic respiratory infections in infants and children. The lung
      itself is rarely sampled directly, and sputum representing lower-airway
      secretions can rarely be obtained from children. In addition culture of
      secretions from upper respiratory tract is not useful since the normal flora
      includes the bacteria commonly responsible for pneumonia. Clinical and radiology
      data only suggest the diagnosis. The development of techniques to detect antigens
      of the causative agent in nasopharyngeal secretions, nucleic acid by means of the
      polymerise-chain reaction assays has significantly improved the identification of
      the responsible pathogen and the choice of appropriate treatment. Since more 30
      years rhinovirus, coronavirus, enterovirus, parainfluenza virus and respiratory
      syncytial virus were added to influenza, adenovirus and measles virus as causes
      of respiratory tract infections. This list of pathogens was extended last years
      with the discovery of human metapneumovirus, bocavirus, polyomavirus. In
      restricted patient groups, such as the immunocompromised, members of the family
      of herpesvirus have also been associated with respiratory disease.

PMID- 18092719
TI  - [Recurrent upper respiratory tract infections and otitis in children].
AB  - Recurrent upper respiratory tract infections should be considered as a normal
      process in infants who build immune defenses in an environment where they meet
      viruses. Nasal lavage with saline serum and the blowing when possible are the
      only treatment justified in all the cases. Antibiotic treatment is not justified.
      It does not shorten the course and does not prevent complications. Recurrent
      otitis media (three episodes in six months or four in one year) are the most
      common complication. Bacterial superinfections are due to bacteria who colonise
      nasopharynx. Facilitating factors for recurrent ENT infections in children are
      individual: age, sex, martial deficiency, gastro-oesophageal reflux, adenoid
      growths. Other facilitating factors are environmental: absence or short duration
      of breast-feading, pollution, passive smoking, day care center. In the great
      majority of cases, laboratory tests are unnecessary. The most important is to
      reassure because recurrent upper respiratory infections improve with time.
      Different facilitating factors previously described have to be taken into account
      and should allow to decrease the number of episodes.

PMID- 18092720
TI  - [Pharyngitis in children].
AB  - The care strategy of pharyngitis has been changed dramatically these last years.
      Because of evolution of antibiotic resistance, the attitude which prevailed of
      the systematic treatment of pharyngitis in order to prevent a hypothetical acute
      rheumatic fever, could not persist. Discrimination between pharyngitis due to
      group A streptococcus (GAS) and nonstreptococcal pharyngitis (usually of viral
      causes) cannot be made in a reliable way by the clinical signs and symptoms, even
      if clinical scores are used. The free availability to practitioners of GAS rapid
      diagnostic tests, sensitive (>90%) and specific (>95%), changes the rule by
      simplifying it: pharyngitis with positive test must be treated with antibiotics,
      those with negative test should not be received such treatment. A reduction of
      two thirds of antibiotics consumption for pharyngitis can be expected, while
      maintaining the benefit (improvement of the clinical signs, reduction of
      contagiousness and the complications) for the patients for whom it is necessary.
      Because of GAS resistance to macrolides and the absence of resistance to beta
      lactam antibiotics, a compound belonging of this last family should be prescribed
      and for a short treatment duration: amoxicillin (50 mg/kg/j, b.i.d for 6 days),
      cefpodoxime proxetil (8 mg/kg/j b.i.d for 5 days), cefuroxime axetil (30 mg/kg/j
      b.i.d for 4 days).

PMID- 18092721
TI  - [Acute rhinosinusitis in children].
AB  - Rhinosinusitis in children is mainly caused by virus. After medical examination
      and according to the evolution, two clinical situations are defined: sub acute
      and persisting rhinosinusitis or acute and severe rhinosinusitis. Due to the
      development of sinus cavities, location of rhinosinusitis varies with age,
      ethmoiditis being the first location in young child. Imaging is recommended in
      cases of severe symptomatology or extra maxillary locations or for complications.
      Antibiotherapy is recommended in severe cases or complications. The choice of
      drugs is supported by the bacterial epidemiology of these infections and the
      level of resistance in France of the different microorganisms involved. In other
      cases, management includes symptomatic treatment and obvious informations on the
      different modalities of evolution.

PMID- 18092722
TI  - [Child acute otitis media].
AB  - Most frequent complication of children upper respiratory tract infections, acute
      otitis media is the leading cause of bacterial infections and one of the leading
      causes of antibiotic prescriptions. Under the combined effect of Prevenar
      immunization and the reduction of the use of antibiotics in France, the highly
      resistant strains of pneumococci (those which posed therapeutic problems)
      decreased moreover of the three quarter. Non typable H. influenzae became the
      main bacteria responsible of AOM, and resistance to the beta-lactams by change of
      penicillin binding proteins is an emergent problem in France. The diagnosis of
      purulent OMA is based on a triad: recent onset functional (otalgia) and generals
      (fever) signs, middle ear effusion and tympanic membrane inflammation. The
      official French guidelines suggest prescribing antibiotics (amoxicillin-acid
      clavulanate-cefpodoxime proxetil) only for purulent acute otitis media diagnosed
      in an unquestionable way, systematically in the child of less than two years,
      only for the most symptomatic forms after this age, while making use of the
      history and the clinical and bacteriological correlations to choose antibiotic.

PMID- 18092723
TI  - [Acute laryngitis and epiglottitis in children].
AB  - The anatomical characteristic of the pediatric larynx allows physicians to better
      understand the incidence of symptomatic and severe presentations of acute
      laryngitis, which are frequent pediatric emergencies. Subglottis laryngitis and
      epiglottitis must be distinguished from each other. These two diseases are
      absolutely different: the first one is essentially viral and usually moderate,
      even though acute respiratory distress can occur. The other (epiglottitis) is
      bacterial, essentially caused by Haemophilus influenza B (Hi-B), and can be life
      threatening. The anti Hi-B vaccine leads to a decrease of frequency but does not
      make them disappear. Moreover, even if a child has a history of the Hi-B vaccine,
      diagnosis of epiglottitis can not to be ruled out. Lastly, in case of acute
      laryngeal dyspnea in a child, one must think about a foreign body.

PMID- 18092724
TI  - [Lavage of the nasal cavity].

PMID- 18092725
TI  - [Two senior advisors, one synthesis and one priority for students].

PMID- 18092726
TI  - [Urinary stones].

PMID- 18092727
TI  - [Vomiting in the newborn, and in the child (with treatment)].

PMID- 18092728
TI  - [Mental handicap. Administrative supervision, trusteeship, safeguard of justice].

PMID- 18092729
TI  - [Amenorrhoea].

PMID- 18092730
TI  - [Sport and health. Sport aptitude in children and adults. Nutritional needs in
      sportsmen].

PMID- 18092731
TI  - [Scientific study of "Joan of Arc relics". The jar from Chinon].

PMID- 18092732
TI  - Bayesian kernel methods for analysis of functional neuroimages.
AB  - We propose an approach to analyzing functional neuroimages in which 1) regions of
      neuronal activation are described by a superposition of spatial kernel functions,
      the parameters of which are estimated from the data and 2) the presence of
      activation is detected by means of a generalized likelihood ratio test (GLRT).
      Kernel methods have become a staple of modern machine learning. Herein, we show
      that these techniques show promise for neuroimage analysis. In an on-off design,
      we model the spatial activation pattern as a sum of an unknown number of kernel
      functions of unknown location, amplitude, and/or size. We employ two Bayesian
      methods of estimating the kernel functions. The first is a maximum a posteriori
      (MAP) estimation method based on a Reversible-Jump Markov-chain Monte-Carlo
      (RJMCMC) algorithm that searches for both the appropriate model complexity and
      parameter values. The second is a relevance vector machine (RVM), a kernel
      machine that is known to be effective in controlling model complexity (and thus
      discouraging overfitting). In each method, after estimating the activation
      pattern, we test for local activation using a GLRT. We evaluate the results using
      receiver operating characteristic (ROC) curves for simulated neuroimaging data
      and example results for real fMRI data. We find that, while RVM and RJMCMC both
      produce good results, RVM requires far less computation time, and thus appears to
      be the more promising of the two approaches.

PMID- 18092733
TI  - Sparse decomposition and modeling of anatomical shape variation.
AB  - Recent advances in statistics have spawned powerful methods for regression and
      data decomposition that promote sparsity, a property that facilitates
      interpretation of the results. Sparse models use a small subset of the available
      variables and may perform as well or better than their full counterparts if
      constructed carefully. In most medical applications, models are required to have
      both good statistical performance and a relevant clinical interpretation to be of
      value. Morphometry of the corpus callosum is one illustrative example. This paper
      presents a method for relating spatial features to clinical outcome data. A set
      of parsimonious variables is extracted using sparse principal component analysis,
      producing simple yet characteristic features. The relation of these variables
      with clinical data is then established using a regression model. The result may
      be visualized as patterns of anatomical variation related to clinical outcome. In
      the present application, landmark-based shape data of the corpus callosum is
      analyzed in relation to age, gender, and clinical tests of walking speed and
      verbal fluency. To put the data-driven sparse principal component method into
      perspective, we consider two alternative techniques, one where features are
      derived using a model-based wavelet approach, and one where the original
      variables are regressed directly on the outcome.

PMID- 18092734
TI  - A comparison framework for breathing motion estimation methods from 4-D imaging.
AB  - Motion estimation is an important issue in radiation therapy of moving organs. In
      particular, motion estimates from 4-D imaging can be used to compute the
      distribution of an absorbed dose during the therapeutic irradiation. We propose a
      strategy and criteria incorporating spatiotemporal information to evaluate the
      accuracy of model-based methods capturing breathing motion from 4-D CT images.
      This evaluation relies on the identification and tracking of landmarks on the 4-D
      CT images by medical experts. Three different experts selected more than 500
      landmarks within 4-D CT images of lungs for three patients. Landmark tracking was
      performed at four instants of the expiration phase. Two metrics are proposed to
      evaluate the tracking performance of motion-estimation models. The first metric
      cumulates over the four instants the errors on landmark location. The second
      metric integrates the error over a time interval according to an a priori
      breathing model for the landmark spatiotemporal trajectory. This latter metric
      better takes into account the dynamics of the motion. A second aim of this paper
      is to estimate the impact of considering several phases of the respiratory cycle
      as compared to using only the extreme phases (end-inspiration and end
      expiration). The accuracy of three motion estimation models (two image
      registration-based methods and a biomechanical method) is compared through the
      proposed metrics and statistical tools. This paper points out the interest of
      taking into account more frames for reliably tracking the respiratory motion.

PMID- 18092735
TI  - Polyp enhancing level set evolution of colon wall: method and pilot study.
AB  - Computer aided detection (CAD) in computed tomography colonography (CTC) aims at
      detecting colonic polyps that are the precursors of colon cancer. In this work,
      we propose a colon wall evolution algorithm polyp enhancing level sets (PELS)
      based on the level-set formulation that regularizes and enhances polyps as a
      preprocessing step to CTC CAD algorithms. The underlying idea is to evolve the
      polyps towards spherical protrusions on the colon wall while keeping other
      structures, such as haustral folds, relatively unchanged and, thereby,
      potentially improve the performance of CTC CAD algorithms, especially for smaller
      polyps. To evaluate our methods, we conducted a pilot study using an arbitrarily
      chosen CTC CAD method, the surface normal overlap (SNO) CAD algorithm, on a nine
      patient CTC data set with 47 polyps of sizes ranging from 2.0 to 17.0 mm in
      diameter. PELS increased the maximum sensitivity by 8.1% (from 21/37 to 24/37)
      for small polyps of sizes ranging from 5.0 to 9.0 mm in diameter. This is
      accompanied by a statistically significant separation between small polyps and
      false positives. PELS did not change the CTC CAD performance significantly for
      larger polyps.

PMID- 18092737
TI  - Incorporating domain knowledge into the fuzzy connectedness framework:
      application to brain lesion volume estimation in multiple sclerosis.
AB  - A method for incorporating prior knowledge into the fuzzy connectedness image
      segmentation framework is presented. This prior knowledge is in the form of
      probabilistic feature distribution and feature size maps, in a standard
      anatomical space, and "intensity hints" selected by the user that allow for a
      skewed distribution of the feature intensity characteristics. The fuzzy affinity
      between pixels is modified to encapsulate this domain knowledge. The method was
      tested by using it to segment brain lesions in patients with multiple sclerosis,
      and the results compared to an established method for lesion outlining based on
      edge detection and contour following. With the fuzzy connections (FC) method, the
      user is required to identify each lesion with a mouse click, to provide a set of
      seed pixels. The algorithm then grows the features from the seeds to define the
      lesions as a set of objects with fuzzy connectedness above a preset threshold.
      The FC method gave improved interobserver reproducibility of lesion volumes, and
      the set of pixels determined to be lesion was more consistent compared to the
      contouring method. The operator interaction time required to evaluate one subject
      was reduced from an average of 111 min with contouring to 16 min with the FC
      method.

PMID- 18092736
TI  - Surface-constrained volumetric brain registration using harmonic mappings.
AB  - In order to compare anatomical and functional brain imaging data across subjects,
      the images must first be registered to a common coordinate system in which
      anatomical features are aligned. Intensity-based volume registration methods can
      align subcortical structures well, but the variability in sulcal folding patterns
      typically results in misalignment of the cortical surface. Conversely, surface
      based registration using sulcal features can produce excellent cortical alignment
      but the mapping between brains is restricted to the cortical surface. Here we
      describe a method for volumetric registration that also produces an accurate one
      to-one point correspondence between cortical surfaces. This is achieved by first
      parameterizing and aligning the cortical surfaces using sulcal landmarks. We then
      use a constrained harmonic mapping to extend this surface correspondence to the
      entire cortical volume. Finally, this mapping is refined using an intensity-based
      warp. We demonstrate the utility of the method by applying it to T1-weighted
      magnetic resonance images (MRIs). We evaluate the performance of our proposed
      method relative to existing methods that use only intensity information; for this
      comparison we compute the intersubject alignment of expert-labeled subcortical
      structures after registration.

PMID- 18092738
TI  - A reconstruction method for gappy and noisy arterial flow data.
AB  - Proper orthogonal decomposition (POD), Kriging interpolation, and smoothing are
      applied to reconstruct gappy and noisy data of blood flow in a carotid artery.
      While we have applied these techniques to clinical data, in this paper in order
      to rigorously evaluate their effectiveness we rely on data obtained by
      computational fluid dynamics (CFD). Specifically, gappy data sets are generated
      by removing nodal values from high-resolution 3-D CFD data (at random or in a
      fixed area) while noisy data sets are formed by superimposing speckle noise on
      the CFD results. A combined POD-Kriging procedure is applied to planar data sets
      mimicking coarse resolution "ultrasound-like" blood flow images. A method for
      locating the vessel wall boundary and for calculating the wall shear stress (WSS)
      is also proposed. The results show good agreement with the original CFD data. The
      combined POD-Kriging method, enhanced by proper smoothing if needed, holds great
      potential in dealing effectively with gappy and noisy data reconstruction of in
      vivo velocity measurements based on color Doppler ultrasound (CDUS) imaging or
      magnetic resonance angiography (MRA).

PMID- 18092739
TI  - Accounting for signal loss due to dephasing in the correction of distortions in
      gradient-echo EPI via nonrigid registration.
AB  - Gradient-echo (GE) echo planar imaging (EPI) is susceptible to both geometric
      distortions and signal loss. This paper presents a retrospective correction
      approach based on nonrigid image registration. A new physics-based intensity
      correction factor derived to compensate for intravoxel dephasing in GE EPI images
      is incorporated into a previously reported nonrigid registration algorithm.
      Intravoxel dephasing causes signal loss and thus intensity attenuation in the
      images. The new rephasing factor we introduce, which changes the intensity of a
      voxel in images during the registration, is used to improve the accuracy of the
      intensity-based nonrigid registration method and mitigate the intensity
      attenuation effect. Simulation-based experiments are first used to evaluate the
      method. A magnetic resonance (MR) simulator and a real field map are used to
      generate a realistic GE EPI image. The geometric distortion computed from the
      field map is used as the ground truth to which the estimated nonrigid deformation
      is compared. We then apply the algorithm to a set of real human brain images. The
      results show that, after registration, alignment between EPI and multi-shot, spin
      echo images, which have relatively long acquisition times but negligible
      distortion, is improved and that signal loss caused by dephasing can be
      recovered.

PMID- 18092740
TI  - Point-based rigid-body registration using an unscented Kalman filter.
AB  - We present and validate a novel registration algorithm mapping two data sets,
      generated from a rigid object, in the presence of Gaussian noise. The proposed
      method is based on the Unscented Kalman Filter (UKF) algorithm that is generally
      employed for analyzing nonlinear systems corrupted by additive Gaussian noise.
      First, we employ our proposed registration algorithm to fit two randomly
      generated data sets in the presence of isotropic Gaussian noise, when the
      corresponding points between the two data sets are assumed to be known. Then, we
      extend the registration method to the case where the data (with known
      correspondences) is stimulated by anisotropic Gaussian noise. The new
      registration method not only reliably converges to the correct registration
      solution, but it also estimates the variance, as a confidence measure, for each
      of the estimated registration transformation parameters. Furthermore, we employ
      the proposed registration algorithm for rigid-body, point-based registration
      where corresponding points between two registering data sets are unknown. The
      algorithm is tested on point data sets which are garnered from a pelvic cadaver
      and a scaphoid bone phantom by means of computed tomography (CT) and tracked free
      hand ultrasound imaging. The collected 3-D points in the ultrasound frame are
      registered to the 3-D meshes in the CT frame by using the proposed and the
      standard Iterative Closest Points (ICP) registration algorithms. Experimental
      results demonstrate that our proposed method significantly outperforms the ICP
      registration algorithm in the presence of additive Gaussian noise. It is also
      shown that the proposed registration algorithm is more robust than the ICP
      registration algorithm in terms of outliers in data sets and initial misalignment
      between the two data sets.

PMID- 18092741
TI  - Detection of anatomic structures in human retinal imagery.
AB  - The widespread availability of electronic imaging devices throughout the medical
      community is leading to a growing body of research on image processing and
      analysis to diagnose retinal disease such as diabetic retinopathy (DR).
      Productive computer-based screening of large, at-risk populations at low cost
      requires robust, automated image analysis. In this paper we present results for
      the automatic detection of the optic nerve and localization of the macula using
      digital red-free fundus photography. Our method relies on the accurate
      segmentation of the vasculature of the retina followed by the determination of
      spatial features describing the density, average thickness, and average
      orientation of the vasculature in relation to the position of the optic nerve.
      Localization of the macula follows using knowledge of the optic nerve location to
      detect the horizontal raphe of the retina using a geometric model of the
      vasculature. We report 90.4% detection performance for the optic nerve and 92.5%
      localization performance for the macula for red-free fundus images representing a
      population of 345 images corresponding to 269 patients with 18 different
      pathologies associated with DR and other common retinal diseases such as age
      related macular degeneration.

PMID- 18092742
TI  - Progress in multimodality imaging: truly simultaneous ultrasound and magnetic
      resonance imaging.
AB  - Multimodality medical imaging takes advantage of the strengths of different
      imaging modalities to provide a more complete picture of the anatomy under
      investigation. Many complementary modalities have been combined to form such
      systems and some are gaining use clinically. One combination that has not been
      developed, in large part due to technical difficulties, is a combined magnetic
      resonance (MR) and ultrasound (US) imaging system. Such a system offers the
      potential to combine the strengths of these modalities in a wide range of
      diagnostic and therapeutic applications. The goal of this study was to evaluate
      the feasibility of performing simultaneous multimodality US and MR imaging. An US
      imaging system capable of operation in a clinical MR imager was developed, and
      methods to perform simultaneous imaging were investigated. Simultaneous imaging
      was feasible without any mutual interference by either filtering the transmitted
      and received US signal, or by synchronizing data acquisition between the two
      imaging systems. Spatial registration between the two modalities was achieved by
      using a reference phantom with implanted glass beads in orthogonal planes.
      Excellent agreement was observed between spatial measurements of an object made
      with both modalities, and the feasibility of using this system in vivo was
      demonstrated in a rabbit model. Simultaneous US and MR imaging is achievable, and
      can provide complementary information about an object under investigation. This
      demonstration of technical feasibility and the development of a prototype system
      open up the potential to investigate the promising clinical applications of this
      combined technology.

PMID- 18092743
TI  - Optimizing size and copy number for PEG-fMLF (N-formyl-methionyl-leucyl
      phenylalanine) nanocarrier uptake by macrophages.
AB  - Curing HIV-1 infection has remained elusive because of low and fluctuating drug
      levels arising from poor absorption, the development of viral reservoirs and
      sanctuary sites, toxicity, and patient nonadherence. The present study addresses
      the issue of insufficient drug exposure in macrophages. Viral reservoir sites
      such as macrophages are believed to be responsible for the viral rebound effect
      observed upon the discontinuation of anti-HIV drug therapy. In our proposed
      model, a drug can be covalently attached to a nanocarrier in order to facilitate
      the delivery of therapeutic agents to the site(s) of infection. As an initial
      step, we propose the covalent attachment of several copies of N-formyl-Met-Leu
      Phe (fMLF), a known chemo-attractant for macrophages. In this article, one or
      more copies of fMLF were conjugated to multifunctional commercially available or
      novel, peptide-based PEG nanocarriers in which the structure was varied by
      appending PEGs with average molecular weights of 5, 20, and 40 kDa. U937 cell
      specific binding and cellular uptake were analyzed. The results of uptake studies
      indicate that (i) uptake is energy dependent and mediated by a fMLF receptor,
      (ii) appending only 2 copies of the targeting ligand to the multifunctional
      nanocarrier appears sufficient for binding in vitro, and (iii) of the three
      configurations studied, the nanocarrier with a molecular weight of about 20 kDa,
      corresponding to a size of 20-60 nm, demonstrated the highest uptake. The results
      of the current studies demonstrate the feasibility of targeting macrophages and
      the suitability of using these synthetically versatile peptide--backbone PEG
      nanocarriers. The convenience, flexibility and possible limitations of this
      nanocarrier approach are discussed.

PMID- 18092744
TI  - Comparison of a tartaric acid derived polymeric MRI contrast agent to a small
      molecule model chelate.
AB  - Contrast agents with high relaxivity are needed to increase the sensitivity of
      magnetic resonance imaging (MRI) for novel clinical and research applications.
      For this reason, polymeric structures containing multiple Gd(III) chelates are of
      current interest. Described in this communication are the syntheses and
      characterization of a glycopolymer derived from L-tartaric acid, Gd 4(H2O), as
      well as a low molecular weight compound, Gd 10(H2O), that models the Gd(III)
      chelate structure in the repeat unit of polymer Gd 4(H2O). Luminescence lifetime
      measurements in H2O and D2O for Eu(III) analogues of Gd 4(H2O) and Gd 10(H2O)
      [named Eu 4(H2O) and Eu 10(H2O)] reveal that the lanthanide in both structures
      likely has one water ligand in the primary coordination sphere. The relaxivity of
      the model chelate Gd 10(H 2O) at 400 MHz and 310 K was determined to be 4.7 mmol
      (-1).s (-1), representing a nearly 50% increase over Magnevist (3.2 mmol (-1).s (
      1)). Relaxivity values on a per Gd basis for the polymeric structure Gd 4(H2O)
      prepared at two degrees of polymerization, n = 12 and 19, are similar, but
      slightly lower than Gd 10(H2O) (4.4 mmol (-1).s (-1) and 4.5 mmol (-1).s (-1),
      respectively). However, their molecular relaxivities of 51 mmol (-1).s (-1) and
      80 mmol (-1).s (-1), respectively, provide a substantial increase over that of
      Magnevist.

PMID- 18092745
TI  - Deriving the probabilities of water loss and ammonia loss for amino acids from
      tandem mass spectra.
AB  - In protein identification through tandem mass spectrometry, it is critical to
      accurately predict the theoretical spectrum for a peptide sequence. The widely
      used prediction models, such as SEQUEST and MASCOT, ignore the intensity of the
      ions with important neutral losses, including water loss and ammonia loss.
      However, ignoring these neutral losses results in a significant deviation between
      the predicted theoretical spectrum and its experimental counterpart. Here, based
      on the "one peak, multiple explanations" observation, we proposed an expectation
      maximization (EM) method to automatically learn the probabilities of water loss
      and ammonia loss for each amino acid. Then we employed these probabilities to
      design an improved statistical model for theoretical spectrum prediction. We
      implemented these methods and tested them on practical data. On a training set
      containing 1803 spectra, the experimental results show a good agreement with some
      known knowledge about neutral losses, such as the tendency of water loss from
      Asp, Glu, Ser, and Thr. Furthermore, on a testing set containing 941 spectra, the
      improved similarity between the experimental and predicted spectra demonstrates
      that this method can generate more reasonable predictions relative to the model
      that ignores neutral losses. As an application of the derived probabilities, we
      implemented a database searching method adopting the improved theoretical
      spectrum model with neutral loss ions estimated. Experimental results on Keller's
      data set demonstrate that this method can identify peptides more accurately than
      SEQUEST. In another application to validate SEQUEST's results, the reported
      peptide-spectrum pairs are reranked with respect to the similarity between
      experimental and predicted spectra. Experimental results on both LTQ and QSTAR
      data sets suggest that this reranking strategy can effectively distinguish the
      false negative predictions reported by SEQUEST.

PMID- 18092747
TI  - Metabolic conversion of dietary quercetin from its conjugate to active aglycone
      following the induction of hepatocarcinogenesis in fisher 344 rats.
AB  - Quercetin exhibits a potent anticarcinogenic activity. However, ingested
      quercetin circulates as the glucuronide/sulfate conjugates, which are less active
      compared to the aglycone in healthy individuals. This study aimed to develop
      further understandings of the cancer-preventing mechanism with dietary quercetin.
      According to a two-stage hepatocarcinogenesis model with N-diethylnitrosamine
      (DEN) and phenobarbital (PB), preneoplasms were induced specifically in the liver
      of Fisher 344 rats. In the liver, glutathione S-transferase placental form (GST
      P) positive foci were produced 14 weeks later. beta-Glucuronidase activity
      increased significantly in the liver by 1.2-fold in the DEN/PB group compared to
      the activity in a saline group. In the kidney, thymus, lung, heart, and plasma,
      the activities were similar between both groups. When quercetin was dosed
      intragastrically 15 min before sacrifice, the aglycone level of quercetin in
      liver was significantly 1.9-fold higher in the DEN/PB group than in the saline
      group. On the other hand, quercetin was dosed to rats 3 times a week for 14
      weeks. The treatment kept the aglycone level of quercetin at a significantly
      higher level and tended to suppress the formation of GST-P positive foci. The
      increase in beta-glucuronidase activity with carcinogenesis induction became
      insignificant following the frequent doses of quercetin. It was considered that
      quercetin aglycone played a preventative role and, thus, the conjugates were
      converted to the active aglycone by beta-glucuronidase that was induced by the
      generation of preneoplasms.

PMID- 18092746
TI  - Application of proteomics in the discovery of candidate protein biomarkers in a
      diabetes autoantibody standardization program sample subset.
AB  - Novel biomarkers of type 1 diabetes must be identified and validated in initial,
      exploratory studies before they can be assessed in proficiency evaluations.
      Currently, untargeted "-omics" approaches are underutilized in profiling studies
      of clinical samples. This report describes the evaluation of capillary liquid
      chromatography (LC) coupled with mass spectrometry (MS) in a pilot proteomic
      analysis of human plasma and serum from a subset of control and type 1 diabetic
      individuals enrolled in the Diabetes Autoantibody Standardization Program, with
      the goal of identifying candidate biomarkers of type 1 diabetes. Initial high
      resolution capillary LC-MS/MS experiments were performed to augment an existing
      plasma peptide database, while subsequent LC-FTICR studies identified
      quantitative differences in the abundance of plasma proteins. Analysis of LC
      FTICR proteomic data identified five candidate protein biomarkers of type 1
      diabetes. alpha-2-Glycoprotein 1 (zinc), corticosteroid-binding globulin, and
      lumican were 2-fold up-regulated in type 1 diabetic samples relative to control
      samples, whereas clusterin and serotransferrin were 2-fold up-regulated in
      control samples relative to type 1 diabetic samples. Observed perturbations in
      the levels of all five proteins are consistent with the metabolic aberrations
      found in type 1 diabetes. While the discovery of these candidate protein
      biomarkers of type 1 diabetes is encouraging, follow up studies are required for
      validation in a larger population of individuals and for determination of
      laboratory-defined sensitivity and specificity values using blinded samples.

PMID- 18092748
TI  - Solvent-free enzymatic preparation of feruloylated monoacylglycerols optimized by
      response surface methodology.
AB  - The ability of immobilized lipase B from Candida antarctica (Novozym 435) to
      catalyze the direct esterification of glyceryl ferulate (FG) and oleic acid for
      feruloylated monoacylglycerols (FMAG) preparation in a solvent-free system was
      investigated. Enzyme screening and the effect of glycerol on the initial reaction
      rate of esterification were also investigated. Response surface methodology (RSM)
      was used to optimize the effects of the reaction temperature (55-65 degrees C),
      the enzyme load (8-14%; relative to the weight of total substrates), oleic
      acid/(FG + glycerol) (6:1-9:1; w/w), and the reaction time (1-2 h) on the
      conversion of FG and yield of FMAG. Validation of the RSM model was verified by
      the good agreement between the experimental and the predicted values of FG
      conversion and FMAG yield. The optimum preparation conditions were as follows:
      temperature, 60 degrees C; enzyme load, 8.2%; substrate ratio, 8.65:1 (oleic
      acid/(FG + glycerol), w/w); and reaction time, 1.8 h. Under these conditions, the
      conversion of FG and yield of FMAG are 96.7 +/- 1.0% and 87.6 +/- 1.2%,
      respectively.

PMID- 18092750
TI  - Characterization of a thermostable extracellular beta-glucosidase with activities
      of exoglucanase and transglycosylation from Paecilomyces thermophila.
AB  - The purification and characterization of a novel extracellular beta-glucosidase
      from Paecilomyces thermophila J18 was studied. The beta-glucosidase was purified
      to 105-fold apparent homogeneity with a recovery yield of 21.7% by DEAE 52 and
      Sephacryl S-200 chromatographies. Its molecular masses were 116 and 197 kDa when
      detected by SDS-PAGE and gel filtration, respectively. It was a homodimeric
      glycoprotein with a carbohydrate content of 82.3%. The purified enzyme exhibited
      an optimal activity at 75 degrees C and pH 6.2. It was stable up to 65 degrees C
      and in the pH range of 5.0-8.5. The enzyme exhibited a broad substrate
      specificity and significantly hydrolyzed p-nitrophenyl-beta- d-glucopyranoside (
      pNPG), cellobiose, gentiobiose, sophorose, amygdalin, salicin, daidzin, and
      genistin. Moreover, it displayed substantial activity on beta-glucans such as
      laminarin and lichenan, indicating that the enzyme has some exoglucanase
      activity. The rate of glucose released by the purified enzyme from
      cellooligosaccharides with a degree of polymerization (DP) ranging between 2 and
      5 decreased with increasing chain length. Glucose and glucono-delta-lactone
      inhibited the beta-glucosidase competitively with Ki values of 73 and 0.49 mM,
      respectively. The beta-glucosidase hydrolyzed pNPG, cellobiose, gentiobiose,
      sophorose, salicin, and amygdalin, exhibiting apparent Km values of 0.26, 0.65,
      0.77, 1.06, 1.39, and 1.45 mM, respectively. Besides, the enzyme showed
      transglycosylation activity, producing oligosaccharides with higher DP than the
      substrates when cellooligosaccharides were hydrolyzed. These properties make this
      beta-glucosidase useful for various biotechnological applications.

PMID- 18092749
TI  - Effect of alcohols on the stability of iprodione in solution.
AB  - Both primary and secondary alcohols degrade iprodione, 3-(3,5-dichlorophenyl)-N
      (1-methylethyl)-2,4-dioxo-1-imidazolidine carboxamide. Steric hindrance has been
      found to have an inverse effect on the rate of its decomposition, and a fully
      substituted alcohol, such as tert-butanol, does not degrade iprodione due to
      extreme steric hindrance. The instability of iprodione in alcohol was found to be
      a function of the structure of the alcohol. The product, N-(3,5-dichlorophenyl)-3
      (1-methylethyl)-2,4-dioxo-1-imidazolidine carboxamide, is obtained from all of
      the reacting alcohols. Confirmation of this structure came from the consideration
      of its NMR, mass spectral, and elemental analysis data.

PMID- 18092751
TI  - Simultaneous determination of oxidized and reduced glutathione in eel's
      (Monopterus albus) plasma by transient pseudoisotachophoresis coupled with
      capillary zone electrophoresis.
AB  - Both the reduced form of glutathione (GSH) and the oxidized form of glutathione
      (GSSG) in eel's ( Monopterus albus) plasma were for the first time determined by
      transient pseudoisotachophoresis coupled with capillary zone electrophoresis. The
      method of transient pseudoisotachophoresis coupled with capillary zone
      electrophoresis has been thoroughly optimized and adequately evaluated for the
      simultaneous determination of GSH and GSSG in eel's plasma. The detection limits
      (S/N = 3) of the method developed were 0.2 and 0.05 micromol/L for GSH and GSSG,
      respectively. The linearity of the calibration curves was valid in the range of 0
      10 micromol/L GSH and 0-0.70 micromol/L GSSG. The method was simple, fast, and
      reproducible. It was found that the respective concentrations of GSH and GSSG
      were in the range of 9.1-14.5 and 0.31-0.58 micromol/L in the adult eel's plasma,
      and 10.8-17.9 and 0.49 - 0.68 micromol/L in the juvenile eel's plasma of the
      three populations determined. Each blood sample was a composite of five eels. For
      each of the three populations, the concentrations of GSH and GSSG in the adult
      eel's plasma were lower than those in the juvenile eel's plasma, and the
      concentrations of GSH and GSSG in the plasma of population 1 (deep yellow finless
      eels) were higher than those in populations 2 (light yellow finless eels) and 3
      (green finless eels) for either the adult or the juvenile eels.

PMID- 18092752
TI  - Development and application of SINE multilocus and quantitative genetic markers
      to study oilseed rape (Brassica napus L.) crops.
AB  - A genetic marker system based on the S1 Short Interspersed Elements (SINEs) in
      the important commercial crop, oilseed rape ( Brassica napus L.) has been
      developed. SINEs provided a successful multilocus, dominant marker system that
      was capable of clearly delineating winter- and spring-type crop varieties.
      Sixteen of 20 varieties tested showed unique profiles from the 17 polymorphic
      SINE markers generated. The 3' or 5' flank region of nine SINE markers were
      cloned, and DNA was sequenced. In addition, one putative pre-transposition SINE
      allele was cloned and sequenced. Two SINE flanking sequences were used to design
      real-time PCR assays. These quantitative SINE assays were applied to study the
      genetic structure of eight fields of oilseed rape crops. Studied fields were more
      genetically diverse than expected for the chosen loci (mean H T = 0.23). The
      spatial distribution of SINE marker frequencies was highly structured in some
      fields, suggesting locations of volunteer impurities within the crop. In one
      case, the assay identified a mislabeling of the crop variety. SINE markers were a
      useful tool for crop genetics, phylogenetics, variety identification, and purity
      analysis. The use and further application of quantitative, real-time PCR markers
      are discussed.

PMID- 18092753
TI  - Determination of antioxidant activity and characterization of antioxidant
      phenolics in the plum vinegar extract of cherry blossom (Prunus lannesiana).
AB  - Sakura-cha (salted cherry blossom tea) is a Japanese tea that is traditionally
      served at celebrations such as wedding ceremonies. The production of Sakura-cha
      includes the immersion of cherry blossom flowers in Japanese plum vinegar, and
      through this process, the byproduct (plum vinegar extract of cherry blossom) is
      obtained. In this study, the antioxidant activity of the plum vinegar extract of
      cherry blossom was examined. The plum vinegar extract of cherry blossom had a
      greater superoxide anion scavenging activity compared with red wine, which is a
      well-known strong antioxidant. Liquid chromatography-mass spectrometry analysis
      showed that cyanidin-3-glucoside, cyanidin-3-rutinoside, and caffeic acid were
      the major components in the phenolic extract prepared from plum vinegar extract
      of cherry blossom, and they possessed superoxide anion scavenging activity.
      Caffeic acid is mainly responsible for the scavenging activity of phenolic
      extract; the contributions of cyanidin-3-glucoside and cyanidin-3-rutinoside were
      minor.

PMID- 18092754
TI  - Dose formulation and analysis of diapocynin.
AB  - Procedures based on high-performance liquid chromatography (HPLC) with
      ultraviolet (UV) detection and liquid chromatography-mass spectrometry (LC-MS)
      are described for analyzing diapocynin. Diapocynin was synthesized by oxidative
      coupling of two apocynin monomers, through the in situ generation of sulfate
      radicals. It was purified by washing 3 times each with boiling water, followed by
      boiling methanol. HPLC was used to determine the concentration of unreacted
      apocynin and other impurities and the purity of the diapocynin that had been
      synthesized. Negative-ion, atmospheric pressure chemical ionization (APCI) LC-MS
      was used to determine the molecular weights of impurities. The method using HPLC
      with UV detection provided a calibration curve that was linear from 0.16 to 24
      microg/mL. The LC-MS method was linear from 0.005 to 2 microg/mL. It was found
      that diapocynin has low solubility in deionized water and corn oil but is soluble
      in dimethylsulfoxide (DMSO) and alkaline aqueous solutions. Also, diapocynin is
      13 times more lipophilic than apocynin, even though both compounds have the same
      p K a of 7.4. The log of the octanol/water partition coefficient (log P) was 1.01
      for apocynin and 1.82 for diapocynin. A solution of 5.5 mg/mL (16.7 mM)
      diapocynin in DMSO was found to be stable for at least 30 days when stored at
      room temperature.

PMID- 18092755
TI  - Creatinine measurements in 24 h urine by liquid chromatography--tandem Mass
      Spectrometry.
AB  - A simple, sensitive, and specific liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method for determining urinary creatinine was developed and used to
      evaluate 24 h urine samples collected during an exposure study. Urine (1 microL)
      was diluted with methanol and then directly applied to LC-MS/MS. Under
      electrospray ionization (ESI) conditions, the transition molecules of creatinine
      and creatinine- d3 were observed at m/ z 114 > 44 and m/ z 117 > 47,
      respectively. The retention time of creatinine was 0.59 min. The linear range was
      1-2000 ng/mL, with a detection limit in urine of 1 ng/mL. LC-MS/MS and
      colorimetric end-point methods were significantly associated ( R2 = 0.8785, p <
      0.0001). The LC-MS/MS method to determine creatinine in 24 h urine samples had
      shorter retention times, was more sensitive, reliable, reproducible, simple,
      selective, and used a smaller sample size than other LC-MS/MS or commercial
      methods.

PMID- 18092756
TI  - Optimizing sampling of tomato fruit for carotenoid content with application to
      assessing the impact of ripening disorders.
AB  - Color defines one aspect of quality for tomato and tomato products. Carotenoid
      pigments are responsible for the red and orange colors of tomato fruit, and thus
      color is also of dietary interest. The aims of this study were (1) to determine
      the relative importance of field sampling and analytical replication when
      measuring lycopene and beta-carotene in tomato fruit and (2) to determine the
      effect of yellow shoulder disorder (YSD) on the content of lycopene and beta
      carotene in tomato juice and tissue. Our results show that increasing biological
      replications is an efficient strategy for reducing the experimental error
      associated with measurements of lycopene and beta-carotene. Analytical
      replications did not contribute significantly to observed variation, and
      therefore experimental efficiency will be gained by reducing analytical
      replications while increasing field replication. We found that YSD significantly
      reduces lycopene in affected tissue and in juice made from affected fruit. In
      contrast, beta-carotene concentrations were only reduced in affected tissue but
      were not significantly reduced in juice. With increasing interest in biofortified
      crops, modulating the carotenoid profile in tomato by minimizing YSD symptoms
      represents a strategy for improving tomato fruit quality that is currently
      supported by grower contract structure and processor grades.

PMID- 18092757
TI  - Protective effects of bilberry (Vaccinium myrtillus L.) extract on KBrO3-induced
      kidney damage in mice.
AB  - Potassium bromate (KBrO3) is an oxidizing agent used as a food additive which
      causes kidney damage as a potent nephrotoxic agent, and the mechanism may be
      explained by the generation of oxygen free radicals. Our experiments showed that
      single intraperitoneal administration of 200 mg/kg KBrO3 could induce serious
      kidney damage, with an increase in serum blood urea nitrogen (BUN) and creatinine
      levels. Five-day oral administration of bilberry ( Vaccinium myrtillus L.)
      extract at 50, 100, and 200 mg/kg resulted in a reversal in serum BUN and
      creatinine to normal levels and decreased kidney malondialdehyde (MDA), nitric
      oxide (NO), and xanthine oxidase (XOD) levels. Also, bilberry extract improved
      oxygen radical absorbance capacity (ORAC) levels in kidney tissue, which showed
      that bilberry extract reduced the degree of oxidative stress and kidney damage
      induced by KBrO3. These findings demonstrate that the protective effect of
      bilberry extract is attributed to its free radical scavenging activity and lipid
      peroxidation inhibitory effect.

PMID- 18092758
TI  - Xylanase inhibitors bind to nonstarch polysaccharides.
AB  - This study is an in-depth investigation of the interaction between
      polysaccharides and the proteinaceous xylanase inhibitors, Triticum aestivum
      xylanase inhibitor (TAXI), xylanase inhibitor protein (XIP), and thaumatin-like
      xylanase inhibitor (TLXI). The binding affinities of all three known types of
      xylanase inhibitors from wheat are studied by measuring the residual xylanase
      inhibition activity after incubation of the inhibitors in the presence of
      different polysaccharides, such as beta-glucans and (arabino)xylans. The binding
      affinities of all three xylanase inhibitors for (arabino)xylans increased with a
      decreasing arabinose/xylose ratio (A/X ratio). This phenomenon was observed both
      with water-extractable and water-unextractable (arabino)xylans. The inhibitors
      also interacted with different soluble and insoluble beta-glucans. None of the
      inhibitors tested had the ability to hydrolyze the polysaccharides investigated.
      The present findings contribute to the unraveling of the function of xylanase
      inhibitors in nature and to the prediction of the effect of added xylanases in
      cereal-based biotechnological processes, such as bread making and gluten-starch
      separation.

PMID- 18092759
TI  - Bioconjugated phospholipid polymer biointerface for enzyme-linked immunosorbent
      assay.
AB  - This study aimed to develop a sensitive and reliable immunoassay by applying a
      highly functional phospholipid polymer biointerface. We synthesized a
      phospholipid polymer--poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n
      butyl methacrylate (BMA)-co-p-nitrophenyloxycarbonyl poly(ethylene glycol)
      methacrylate (MEONP)] (PMBN). MEONP contains active ester groups on the side
      chains for immobilization of antibodies via oxyethylene. PMBN with different
      compositions and oxyethylene chain lengths were synthesized; their effects on
      nonspecific and specific values in the immunoassay were evaluated. MPC units
      reduce the background by preventing nonspecific protein adsorption. MEONP units
      could conjugate antibodies and enhance the specific signal. The specific signal
      was independent of the oxyethylene chain length, but long oxyethylene chains
      increased the background. Specific signals corresponding to the antigen were
      observed with the PMBN coating, and a liner standard curve was obtained. The PMBN
      coated surface maintained residual activity after long-term storage. This surface
      affords a low background without requiring blocking treatment and is suitable for
      immobilized antibodies.

PMID- 18092761
TI  - Photophysics of a xanthenic derivative dye useful as an "on/off" fluorescence
      probe.
AB  - The photophysical behavior of a new fluorescein derivative has been explored by
      using absorption and steady-state and time-resolved fluorescence measurements.
      The influence of ionic strength, as well as total buffer concentration, on both
      the absorbance and fluorescence has been investigated. The apparent acidity
      constant of the dye determined by absorbance is almost independent of the added
      buffer and salt concentrations. A semiempirical model is proposed to rationalize
      the variations in the apparent pKa values. The excited-state proton-exchange
      reaction around the physiological pH becomes reversible upon addition of
      phosphate buffer, inducing a pH-dependent change of the steady-state fluorescence
      and decay times. Fluorescence decay traces, collected as a function of total
      buffer concentration and pH, were analyzed by global compartmental analysis,
      yielding the following values of the rate constants describing excited-state
      dynamics: k01 = 1.29 x 10(10) s(-1), k02 = 4.21 x 10(8) s(-1), k21 approximately
      3 x 10(6) M(-1) s(-1), k12B= 6.40 x 10(8) M(-1) s(-1), and k21B = 2.61 x 10(7) M(
      1) s(-1). The decay rate constant values of k01, k21, k21B, along with the low
      molar absorption coefficient of the neutral form, mean that coupled decays are
      practically monoexponential at buffer concentrations higher than 0.02 M and any
      pH. Thus, the pH and buffer concentration can modulate the main lifetime of the
      dye.

PMID- 18092760
TI  - Morphology of artificial silica matrices formed via autosilification of a
      silaffin/protein polymer chimera.
AB  - Protein polymers (long-chain proteins in which a specific amino acid sequence
      "monomer" is repeated through the molecule) are found widely in nature, and these
      materials exhibit a diverse array of physical properties. One class of self
      assembling proteins is hydrophobic-polar (HP) protein polymers capable of self
      assembly under the appropriate solution conditions. We generated a chimeric
      protein consisting of an HP protein polymer monomer unit, EAK 1 (sequence n
      AEAEAKAKAEAEAKAK-c), and a silaffin peptide, R5 (sequence: n-SSKKSGSYSGSKGSKRRIL
      c). First identified in diatoms, silaffins represent a class of proteins and
      peptides capable of directing silica precipitation in vitro at neutral pH and
      ambient temperatures. The EAK 1-R5 chimera demonstrated self-assembly into
      hydrogels and the ability to direct silica precipitation in vitro. This chimera
      is capable of generating silica morphologies and feature sizes significantly
      different from those achievable with the R5 peptide alone, indicating that
      fusions of silaffins with self-assembling proteins may be a route to controlling
      the morphology of artificially produced silica matrices.

PMID- 18092762
TI  - Experimental and computational studies of nuclear substituted 1,1'-dimethyl-2,2'
      bipyridinium tetrafluoroborates.
AB  - The synthesis and spectral properties of a new 2,2'-bipyridinium ion, 1,1'
      dimethyl-4,4'-(dimethylamino)-2,2'-bipyridinium bis(tetrafluoroborate) are
      reported. Rotation of the dimethylamino group is slow at room temperature on the
      400 MHz 1H and 100 MHz 13C NMR time scales. Complete line shape fit of the
      dynamically broadened NMR spectra was used to determine the activation barriers
      for this process. The first complete set of UV-vis spectra for a 2,2'
      bipyridinium dication and its one- and two-electron reduced products was
      reported. TD-DFT calculations were used to help assign the origin of the long
      wavelength absorptions in these species. The effect of substituents on the
      energies and conformational potential energy surfaces of all three species were
      also examined using the B3LYP/6-31G(d) computational method.

PMID- 18092763
TI  - Freezing of fluids confined between mica surfaces.
AB  - Using grand ensemble simulations, we show that octamethyl-cyclo-tetra-siloxane
      (OMCTS) confined between two mica surfaces can form a variety of frozen phases
      which undergo solid-solid transitions as a function of the separation between the
      surfaces. For atomically smooth mica surfaces, the following sequence of
      transitions 1[triangle up] --> 1[triangle up]b --> 2B --> 2 square --> 2[triangle
      up] are observed in the one- and two-layered regimes, where n[triangle up],
      n[square], and nB denote triangular, square, and buckled phases, respectively,
      with the prefix n denoting the number of confined layers. The presence of
      potassium on mica is seen to have a strong influence on the degree of order
      induced in the fluid. The sequence of solid-solid transitions that occurs with
      the smooth mica surface is no longer observed. When equilibrated with a state
      point near the liquid-solid transition, a counterintuitive freezing scenario is
      observed in the presence of potassium. Potassium disrupts in-plane ordering in
      the fluid in contact with the mica surface, and freezing is observed only in the
      inner confined layers. The largest mica separations at which frozen phases were
      observed ranged from separations that could accommodate six to seven fluid
      layers. The extent of freezing and the square-to-triangular lattice transition
      was found to be sensitive to the presence of potassium as well as the
      thermodynamic conditions of the bulk fluid. The implications of our results on
      interpretation of surface force experiments as well as the generic phase behavior
      of confined soft spheres is discussed.

PMID- 18092764
TI  - Kinetic calibration using dominant pre-equilibrium desorption for on-site and in
      vivo sampling by solid-phase microextraction.
AB  - A new kinetic calibration was developed using dominant pre-equilibrium desorption
      by solid-phase microextracton. The calibration was based on isotropism between
      absorption and desorption, which was proved theoretically and experimentally in
      an aqueous solution and semisolid matrix. This approach allows for the
      calibration of absorption using desorption to compensate for matrix effects.
      Moreover, concentration profiles are initially proposed to verify isotropism
      between the absorption and desorption, while providing a linear approach to
      obtain time constants for the purpose of quantitative analysis. This linear
      approach is more convenient, robust, and accurate than the nonlinear version with
      the previously used time profiles. Furthermore, the target analytes are used as
      the internal standards; thus, radioactive or deuterated internal standards are
      not necessary. In addition, dominant pre-equilibrium desorption utilizes the pre
      equilibrium approach and offers a shorter sample preparation time, which is
      typically suitable for in vivo sampling. This kinetic calibration method was
      successfully applied to prepare samples of polycyclic aromatic hydrocarbons in a
      flow-through system and in vivo pesticide sampling in a jade plant (Crassula
      ovata).

PMID- 18092765
TI  - Competitive immunoassays for simultaneous detection of metabolites and proteins
      using micromosaic patterning.
AB  - New high-throughput immunoassay methods for rapid point-of-care diagnostic
      applications represent an unmet need and current focus of numerous innovative
      methods. We report a new micromosaic competitive immunoassay developed for the
      analysis of the thyroid hormone thyroxine (T4), inflammation biomarker C-reactive
      protein (CRP), and the oxidative damage marker 3-nitrotyrosine (BSA-3NT) on a
      silicon nitride substrate. To demonstrate the versatility of the method, both
      direct and indirect format competitive immunoassays were developed and could be
      applied simultaneously for single samples. Signals from standard solutions were
      fit to a logistic equation, allowing simultaneous detection of T4 (7.7-257.2 nM),
      CRP (0.3-4.2 microg/mL), and BSA-3NT (0.03-22.3 microg/mL). Total assay time
      including sample introduction, washing, and fluorescence measurement was less
      than 45 min. Dissociation constants for affinity pairs in the system have been
      estimated using regression. This proof-of-concept experiment shows that both
      small and macromolecular biomarkers can be quantified from a single sample using
      the method and suggests that groups of clinically related analytes may be
      analyzed by competitive micromosaic immunoassay techniques.

PMID- 18092766
TI  - Photoreactions of Tyr8- and Gln50-mutated BLUF domains of the PixD protein of
      Thermosynechococcus elongatus BP-1: photoconversion at low temperature without
      Tyr8.
AB  - We studied the photoreaction of a blue-light sensor PixD protein of
      Thermosynechococcus elongatus that has the blue-light-using flavin (BLUF) domain.
      The Tyr8 and Gln50 residues of the protein were modified to phenylalanine,
      alanine, or asparagine (Y8F, Y8A, Q50N, and Q50A) by site-directed mutagenesis.
      The following results were obtained. (1) At room temperature, blue-light
      illumination induced the red shift of the absorption bands of flavin in the wild
      type (WT) protein but not in the Y8F, Y8A, Q50A, and Q50N mutant proteins, as
      reported [Okajima, K., et al. (2006) J. Mol. Biol. 363, 10-18]. (2) At 80 K,
      neither the Q50N nor the Q50A mutant protein accumulated the red-shifted form.
      (3) At 80 K, the Y8F protein photoaccumulated the red-shifted forms to an extent
      that was half that in the WT protein at a 43-fold slower rate, and the Y8A
      protein to the one-fourth the extent at a 137-fold slower rate. (4) The red
      shifted form in the Y8F protein was stable below 240 K and became unstable above
      240 K in the dark. (5) The illumination of the Y8F protein at 150 K accumulated
      the red-shifted form at the beginning, and the prolonged illumination accumulated
      the flavin anions by the secondary photoreaction. (6) The results indicate that
      Tyr8 is not indispensable for the accumulation of the red-shifted form at least
      at 80 K. (7) Photoconversion mechanisms in the WT and Tyr8-mutated proteins are
      discussed in relation to the schemes with and without the electron transfer
      between Tyr8 and flavin in the first step of the photoconversion.

PMID- 18092767
TI  - Structure, spectroscopy, and reactivity properties of porphyrin pincers: a
      conceptual density functional theory and time-dependent density functional theory
      study.
AB  - Porphyrin and pincer complexes are both important categories of compounds in
      biological and catalytic systems. The idea to combine them is computationally
      investigated in this work. By employment of density functional theory (DFT),
      conceptual DFT, and time-dependent DFT approaches, structure, spectroscopy, and
      reactivity properties of porphyrin pincers are systematically studied for a
      selection of divalent metal ions. We found that the porphyrin pincers are
      structurally and spectroscopically different from their precursors and are more
      reactive in electrophilic and nucleophilic reactions. A few quantitative
      linear/exponential relationships have been discovered between bonding
      interactions, charge distributions, and DFT chemical reactivity indices. These
      results are implicative in chemical modification of hemoproteins and
      understanding chemical reactivity in heme-containing and other biologically
      important complexes and cofactors.

PMID- 18092768
TI  - QSAR models for the human H(+)/peptide symporter, hPEPT1: affinity prediction
      using alignment-independent descriptors.
AB  - A data set comprising the major known chemical classes of hPEPT1 ligands was
      compiled from the literature. For these compounds, alignment-independent
      descriptors (VolSurf, GRIND/Almond, and MOE) were computed. Using hierarchical
      partial least-squares projection to latent structures (H-PLS), a one-component
      model with r2 = 0.77 and q2 = 0.75 was obtained. The model satisfied a set of
      rigorous validation criteria and performed well in the prediction of an external
      test set. Mechanistic interpretation of the model reveals polarity properties to
      be the dominant factors in determining hPEPT1 affinity, with hydrophobic
      interactions contributing to a lesser extent. The model is superior to previously
      reported models due to its combination of quality and speed. Accordingly, it is
      suitable for ligand-based virtual screening, such as QSAR-based database mining.

PMID- 18092769
TI  - Dynamics of Water in NaxCoO2.yH2O.
AB  - Incoherent inelastic neutron scattering experiments were performed on Na0.7CoO2
      and Na0.28CoO2.1.3H2O in order to understand how the dynamics of the hydrogen
      bond network of water is modified in the triangular crystalline lattice
      NaxCoO2.yH2O. Using quasi-elastic neutron scattering (QENS), we were able to
      differentiate between two types of proton dynamics: a fast process (due to water
      strongly bound into the sodium cobalt oxyhydrate structure during the hydration
      process) and a slow process (likely attributable to a collective motion). High
      resolution QENS experiments, carried out on Na0.28CoO2.1.3H2O, show that, at
      temperatures above 310 K, the water dynamics can be well-described by a random
      jump diffusion model characterized by a diffusion constant equal to 0.9 x 10(
      9)m2/s, which is significantly lower than the rate of diffusion for bulk water.
      Furthermore, our results indicate that, at room temperature, the sodium ions have
      no influence on the rotational dynamics of the "fast" water molecules.

PMID- 18092770
TI  - Ab initio comprehensive conformational analysis of 2'-deoxyuridine, the
      biologically significant DNA minor nucleoside, and reconstruction of its low
      temperature matrix infrared spectrum.
AB  - A comprehensive conformational analysis of isolated 2'-deoxyuridine (dU), a minor
      DNA nucleoside, has been performed by means of ab initio calculations at the
      MP2/6-311++G (d,p)//DFT B3LYP/6-31G (d,p) level of theory. At 298.15 and 420 K,
      all 94 allowed conformers of dU are within 8.96 and 7.91 kcal/mol Gibbs energy
      ranges, respectively. Syn orientation for the base and South (S) conformers for
      the sugar dominate at 298.15 K: syn/anti=62.3%:37.7% and S/N=77.2%:22.8%. At 420
      K in the majority of conformers, the base is anti oriented and the population of
      North (N) sugars increases: syn/anti=39.3%:60.7% and S/N=63.0%:37.0%. Values of
      all conformational parameters and correlations between them, as well as their
      correlations with valence bonds, and also correlations between valence bonds and
      angles were estimated. In general, 14 types of intramolecular H-bonds were
      detected (1-3 H-bonds per conformer, the total number 175), namely, C1'H...O2 (16
      H-bonds), C2'H1...O5' (9), C2'H2...O2 (21), C3'H...O2 (21), C5'H1...O2 (14),
      C5'H2...O2 (11), C6H...O4' (37), C6H...O5' (22), C3'H...HC6 (4), O5'H...HC6 (2),
      O3'H...O5' (5), O5'H...O4' (1), O5'H...O3' (4), and O5'H...O2 (8). Geometric,
      vibrational, structural-topological, and energetic features of the OH...O
      intramolecular H-bonds in dU conformers were determined. The close similarity
      between energetic and geometric characteristics of dU and thymidine DNA-like
      conformers in anti and relevant syn conformations and their transition states of
      the anti-->syn interconversion implies that mismatch DNA glycosylase
      discriminates between the two nucleosides, mainly because of the difference in
      the shapes of their bases. Convolution of calculated IR spectra of all the dU
      conformers within the limits 3400-3700 cm(-1) appears to be consistent with its
      low-temperature matrix IR spectrum (Ivanov et al. Spectrochim. Acta, Part A 2003,
      59, 1959), wavenumber discrepancy not exceeding 1%. It was concluded that, for a
      reliable reproduction of the experimental spectrum, the whole set of conformers
      should be taken into consideration. The suggested method makes reconstruction of
      the isolated nucleoside IR spectrum at a physiological interval of temperature
      reasonably possible.

PMID- 18092771
TI  - Outer-sphere oxidation of the superoxide radical anion.
AB  - Efforts to use the Marcus model to describe oxidations of the superoxide radical
      anion (O(2-)) by transition-metal complexes have failed dramatically, with
      discrepancies between theory and experiment spanning 13 orders of magnitude. As a
      result, the prevailing view is that these reactions involve some complex
      interactions that are not yet understood. We now show that once the familiar form
      of the Marcus cross relation (MCR) is modified to allow for the relatively small
      size of O(2-), excellent agreement is obtained between theory and experiment.
      This simple finding dispels the decades of uncertainty surrounding these
      reactions and provides a reliable method for determining whether oxidations of
      (O2)- occur via inner- or outer-sphere pathways. More generally, the modified MCR
      is applicable to any homogeneous electron-transfer process characterized by
      significant differences in size between electron donors and acceptors.

PMID- 18092772
TI  - Generation and suppression of 3-/4-functionalized benzynes using zinc ate base
      (TMP-Zn-ate): new approaches to multisubstituted benzenes.
AB  - We present full details of our new methods for preparing functionalized benzynes
      with lithium di-alkyl(2,2,6,6-tetramethylpiperidino)zincate (R2Zn(TMP)Li) through
      deprotonative zincation as a key reaction. In this system, by choosing
      appropriate ligands for the zincate, either regioselective zincation of
      functionalized haloaromatics or the generation of substituted benzynes can be
      controlled in good yields with excellent chemoselectivity, using the same
      substrate. Zincation with (t)Bu2Zn(TMP)Li followed by electrophilic trapping or
      zincation with Me2Zn(TMP)Li followed by nucleophilic or diene trapping is shown
      to be a powerful tool for the chemoselective preparation of 1,2,3-/1,2,4
      trisubstituted benzene derivatives. These methods offer far greater generality
      than previous methods for the synthesis of multifunctionalized benzenes.
      Computational/theoretical studies of the reaction mechanism of this unique
      benzyne formation indicated that preferential coordination of the dialkylzinc
      moiety of zincate to halogen is the reason for the reduced activation energy of
      the elimination, that is, for the formation of the benzyne. The role of the
      ligands on Zn in accelerating/decelerating the elimination is also discussed.

PMID- 18092773
TI  - Sequence-specific, dynamic covalent crosslinking in aqueous media.
AB  - This article describes an associating system that integrates the specificity of
      multiple hydrogen bonding and the strength of dynamic covalent interactions.
      Linear oligoamides that sequence-specifically pair into H-bonded duplexes in
      nonpolar solvents were modified with S-trityl groups, allowing the reversible
      formation of disulfide bonds. The disulfide-crosslinking reactions of oligoamides
      capable of pairing via two, four, and six intermolecular H-bonds, along with
      several control strands, were examined using ESI, MALDI-TOF, reverse phase HPLC,
      and two-dimensional NMR. Results from these studies demonstrate that this system
      possesses both the high fidelity of multiply H-bonded assemblies and the high
      stability of covalent interaction, leading to the sequence-specific crosslinking
      of complementary oligoamides in not only nonpolar (methylene chloride) solutions
      but also highly competitive (aqueous) media. Experiments were designed to
      systematically probe the mechanism behind the specific formation of the sequence
      matched products, which revealed a thermodymically controlled process. Multiple
      pairs in the same solution were crosslinked in a sequence-specific fashion. In
      addition, a length-dependent selectivity was also observed. Thus, oligoamides
      with different lengths or sequences did not crosslink into mismatched products.
      As few as two H-bonds is sufficient to bias the specific formation of the
      crosslinked product in aqueous media, suggesting that associating units with
      tunable sizes, high stability, and high specificity can be conveniently designed.
      The combination of H-bonding and dynamic covalent interactions represents a new,
      generalizable strategy for developing highly specific molecular associating units
      that are stable in a wide variety of media. These associating units will greatly
      facilitate the construction of various structures with many applications.

PMID- 18092774
TI  - ENDOR characterization of a synthetic diiron hydrazido complex as a model for
      nitrogenase intermediates.
AB  - Molybdenum-dependent nitrogenase binds and reduces N2 at the [Fe7, Mo, S9, X,
      homocitrate] iron-molybdenum cofactor (FeMo-co). Kinetic and spectroscopic
      studies of nitrogenase variants indicate that a single Fe-S face is the most
      likely binding site. Recently, substantial progress has been made in determining
      the structures of nitrogenase intermediates formed during alkyne and N2 reduction
      through use of ENDOR spectroscopy. However, constraints derived from ENDOR
      studies of biomimetic complexes with known structure would powerfully contribute
      in turning experimentally derived ENDOR parameters into structures for species
      bound to FeMo-co during N2 reduction. The first report of a paramagnetic Fe-S
      compound that binds reduced forms of N2 involved Fe complexes stabilized by a
      bulky beta-diketiminate ligand (Vela, J.; Stoian, S.; Flaschenriem, C. J.; Munck,
      E.; Holland, P. L. J. Am. Chem. Soc. 2004, 126, 4522-4523). Treatment of a
      sulfidodiiron(II) complex with phenylhydrazine gave an isolable mixed-valence
      FeII-Fe(III) complex with a bridging phenylhydrazido (PhNNH2) ligand, and this
      species now has been characterized by ENDOR spectroscopy. Using both 15N, 2H
      labeled and unlabeled forms of the hydrazido ligand, the hyperfine and quadrupole
      parameters of the -N-NH2 moiety have been derived by a procedure that
      incorporates the (near-) mirror symmetry of the complex and involves a strategy
      which combines experiment with semiempirical and DFT computations. The results
      support the use of DFT computations in identifying nitrogenous species bound to
      FeMo-co of nitrogenase turnover intermediates and indicate that 14N quadrupole
      parameters from nitrogenase intermediates will provide a strong indication of the
      nature of the bound nitrogenous species. Comparison of the large 14N hyperfine
      couplings measured here with that of a hydrazine-derived species bound to FeMo-co
      of a trapped nitrogenase intermediate suggests that the ion(s) are not high spin
      and/or that the spin coupling coefficients of the coordinating cofactor iron
      ion(s) in the intermediate are exceptionally small.

PMID- 18092776
TI  - OFF-OFF-ON switching of fluorescence and electron transfer depending on stepwise
      complex formation of a host ligand with guest metal ions.
AB  - Stepwise complex formation is observed between 2,3,5,6-tetrakis(2
      pyridyl)pyrazine (TPPZ) and a series of metal ions (M(n+) = Sc3+, Y3+, Ho3+,
      Eu3+, Lu3+, Nd3+, Zn2+, Mg2+, Ca2+, Ba2+, Sr2+, Li+), where TPPZ forms a 2:1
      complex [(TPPZ)2-M(n+)] and a 1:1 complex [TPPZ-M(n+)] with Mn+ at low and high
      concentrations of metal ions, respectively. The fluorescence intensity of TPPZ
      begins to increase at high concentrations of metal ions, when the 2:1 (TPPZ)2
      M(n+) complex is converted to the fluorescent 1:1 TPPZ-M(n+) complex. This is
      regarded as an "OFF-OFF-ON" fluorescence sensor for metal ions depending on the
      stepwise complex formation between TPPZ and metal ions. The fluorescence quantum
      yields of the TPPZ-M(n+) complex vary depending on the metal valence state, in
      which the fluorescence quantum yields of the divalent metal complexes (TPPZ-M2+)
      are much larger than those of the trivalent metal complexes (TPPZ-M3+). On the
      other hand, the binding constants of (TPPZ)2-M(n+) (K1) and TPPZ-M(n+) (K2) vary
      depending on the Lewis acidity of metal ions (i.e., both K1 and K2 values
      increase with increasing Lewis acidity of metal ions). Sc3+, which acts as the
      strongest Lewis acid, forms the (TPPZ)2-Sc3+ and TPPZ-Sc3+ complexes
      stoichiometrically with TPPZ. In such a case, "OFF-OFF-ON" switching of electron
      transfer from cobalt(II) tetraphenylporphyrin (CoTPP) to O2 is observed in the
      presence of Sc3+ and TPPZ depending on the ratio of Sc3+ to TPPZ. Electron
      transfer from CoTPP to O2 occurs at Sc3+ concentrations above the 1:2 ratio
      ([Sc3+]/[TPPZ]0 > 0.5), when the (TPPZ)2-Sc3+ complex is converted to the TPPZ
      Sc3+ complex and TPPZ-(Sc3+)2, which act as promoters of electron transfer (ON)
      by the strong binding of O2*- with Sc3+. In sharp contrast, no electron transfer
      occurs without metal ion (OFF) or in the presence at Sc3+ concentrations below
      the 1:2 ratio (OFF), when the (TPPZ)2-Sc3+ complex has no binding site available
      for O2*-.

PMID- 18092775
TI  - Structure and magnetism of dinuclear copper(II) metallacyclophanes with
      oligoacenebis(oxamate) bridging ligands: theoretical predictions on wirelike
      magnetic coupling.
AB  - Self-assembly of the ligands N,N'-1,5-naphthalenebis(oxamate) (1,5-naba) and N,N'
      2,6'-anthracenebis(oxamate) (2,6-anba) by Cu(II) ions affords the two new
      dicopper(II) metallacyclophanes 2a and 3b, whereby the metal centers are
      connected by double naphthalene- and anthracenediamidate bridges with
      alpha,alpha' and beta,beta' substitution patterns, respectively. Despite the
      largely different intermetallic distances of 8.3 A (2a) and 12.3 A (3b), magnetic
      susceptibility measurements show a moderately strong antiferromagnetic coupling
      with rather similar J values in the range from -20.5 to -20.7 (2a) and from -21.2
      to -23.0 (3b) cm(-1) (H = -J S1 x S2; S1 = S2 = 1/2). Density functional theory
      calculations on the two series of dicopper(II) metallacyclophanes 1a-10a and 1b
      10b with linear alpha,alpha'- and beta,beta'-disubstituted oligoacenediamidate
      bridges, respectively, confirm the better efficiency of the latter substitution
      pattern on long-range magnetic coupling. More importantly, they predict a
      unprecedented wirelike magnetic behavior for the longest members of the series
      with octacene through decacene spacers (J values up to +3.0 cm(-1) for
      intermetallic distances reaching 28.8 A).

PMID- 18092777
TI  - Comparison of electrical properties of viruses studied by AC capacitance scanning
      probe microscopy.
AB  - Capacitances of five types of viruses, adenovirus type 5 (AV5), herpes simplex
      virus type 1 (HSV1), simian virus 40 (SV40), vaccinia (MVA), and cowpea mosaic
      virus (CPMV), were compared by AC capacitance scanning probe microscopy. This
      technique, using a Pt-coated AFM tip as an electrode to probe capacitance of
      materials between the tip and a bottom electrode, has been applied to study
      surface structures of semiconductors and polymers with nanometer spatial
      resolution; however, biological samples at the nanoscale have not been explored
      by this technique yet. Because most biological cells are poor conductors, this
      approach to probe electric properties of cells by capacitance is logical. This
      scanning probe technique showed that each virus has distinguishable and
      characteristic capacitance. A series of control experiments were carried out
      using mutant viruses to validate the origin of the characteristic capacitance
      responses for different viruses. A mutation on the capsid in HSV1 with green
      fluorescence proteins increased capacitance from 9 x 10(-6) to 1 x 10(-5) F/cm2
      at the frequency of 10(4) Hz. Herpes simplex virus type 2 (HSV2) decreased
      capacitance when its envelope and glycoproteins were chemically extracted. These
      control experiments indicate that dielectric properties of capsid proteins and
      envelope glycoproteins significantly influence overall dielectric constants of
      viruses. Because those capsid proteins and glycoproteins are characteristic of
      the virus strain, this technique could be applied to detect and identify viruses
      at the single viron level using their distinct capacitance spectra as
      fingerprints without labeling.

PMID- 18092778
TI  - Reactivity of hydrogen with solid-state films of alkylamine- and
      tetraoctylammonium bromide-stabilized Pd, PdAg, and PdAu nanoparticles for
      sensing and catalysis applications.
AB  - Hydrogen gas spontaneously adsorbs to Pd metal as atomic hydrogen and diffuses
      into the lattice to form PdHx. We previously showed that films of hexanethiolate
      coated Pd monolayer-protected clusters (MPCs) do not readily react with H2 due to
      the strong chemical bonding of the thiolate to the Pd, which inhibits the
      reaction. Consequently, these films require ozone or heat treatment for
      reactivity to occur, which is inconvenient for sensing or catalysis applications.
      In this report, we describe the reactivity between H2 and solid-state films of
      alkylamine-coated Pd, PdAg (10:1), and PdAu (10:1) MPCs and films of
      tetraoctylammonium bromide (TOABr)-stabilized Pd and PdAg (10:1) nanoparticles as
      determined by changes in film conductivity. Our data show that Pd nanoparticles
      coated with these more weakly coordinated amine or ammonium groups readily react
      with H2 without any need for ozone or heat treatment. The conductivity of films
      of octylamine (C8NH2)- or dodecylamine (C12NH2)-coated Pd, PdAg, and PdAu MPCs
      increases irreversibly upon initial exposure to 100% H2 to varying degrees and
      with different reaction kinetics and then exhibits stable, reversible changes in
      the presence of H2 concentrations ranging from 9.6 to 0.08%. The behavior upon
      initial exposure to H2 (conditioning) and the direction and magnitude of the
      reversible conductivity changes depend on the alkyl chainlength and alloy
      composition. Films of TOABr-coated Pd and PdAg nanoparticles show stable,
      reversible increases in conductivity in the presence of H2 concentrations from
      9.6 down to 0.11% without conditioning. Surface FTIR spectroscopy and atomic
      force microscopy (AFM) provide information about the organic monolayer and film
      morphology, respectively, following reactivity with H2. This work demonstrates a
      simple approach toward preparing films of chemically synthesized Pd-containing
      nanoparticles with controlled reactivity to H2 for sensing and catalysis
      applications.

PMID- 18092779
TI  - Microwave-assisted palladium(0)-catalyzed alkylative cyclization of allenyl
      aldehydes leading to 3-substituted 3-cycloalken-1-ols.

PMID- 18092780
TI  - Discovery and mechanistic study of Al(III)-catalyzed transamidation of tertiary
      amides.
AB  - Cleavage of the C-N bond of carboxamides generally requires harsh conditions.
      This study reveals that tris(amido)Al(III) catalysts, such as Al2(NMe2)6, promote
      facile equilibrium-controlled transamidation of tertiary carboxamides with
      secondary amines. The mechanism of these reactions was investigated by kinetic,
      spectroscopic, and density functional theory (DFT) computational methods. The
      catalyst resting state consists of an equilibrium mixture of a tris(amido)Al(III)
      dimer and a monomeric tris(amido)Al(III)-carboxamide adduct, and the turnover
      limiting step involves intramolecular nucleophilic attack of an amido ligand on
      the coordinated carboxamide or subsequent rearrangement (intramolecular ligand
      substitution) of the tetrahedral intermediate. Fundamental mechanistic
      differences between these tertiary transamidation reactions and previously
      characterized transamidations involving secondary amides and primary amines
      suggest that tertiary amide/secondary amine systems are particularly promising
      for future development of metal-catalyzed amide metathesis reactions that proceed
      via transamidation.

PMID- 18092781
TI  - Unexpected fractionation in site-specific 13C isotopic distribution detected by
      quantitative 13C NMR at natural abundance.

PMID- 18092782
TI  - Budding and asymmetric protein microcompartmentation in giant vesicles containing
      two aqueous phases.
AB  - We report the effect of external osmolarity on giant lipid vesicles containing an
      aqueous two-phase system (ATPS GVs). The ATPS, which is comprised of
      poly(ethyleneglycol) [PEG], dextran, and water, serves as a primitive model of
      the macromolecularly crowded environment of the cytoplasm. Coexisting PEG-rich
      and dextran-rich aqueous phases provide chemically dissimilar microenvironments,
      enabling local differences in protein concentration to be maintained within
      single ATPS GVs. The degree of biomolecule microcompartmentation can be increased
      by exposing the ATPS GVs to a hypertonic external solution, which draws water out
      of the vesicles, concentrating the polymers. Enrichment of a protein, soybean
      agglutinin, in the dextran-rich phase improves from 2.3-fold to 10-fold with an
      increase in external osmolarity from 100 to 200 mmol/kg. In some cases, budding
      occurs, with the bud(s) formed by partial expulsion of one of the two polymer
      rich aqueous phases. Budding results in asymmetry in the internal polymer and
      biomolecule composition, giving rise to polarity in these primitive model cells.
      Budding is observed with increasing frequency as external ionic strength
      increases, when membrane elasticity permits, and can be reversed by decreasing
      external osmolarity. We note that the random symmetry-breaking induced by simple
      osmotic shrinkage resulted in polarity in both the structure and internal protein
      distribution in these primitive model cells. Budding in ATPS-containing GVs thus
      offers an experimental model system for investigating the effects of biochemical
      asymmetry on the length scale of single cells.

PMID- 18092783
TI  - Potentiometric detection of DNA hybridization.

PMID- 18092784
TI  - [2,3-(13)C]-labeling of aromatic residues--getting a head start in the magic
      angle-spinning NMR assignment of membrane proteins.

PMID- 18092785
TI  - Enantioselective, NHC-catalyzed bicyclo-beta-lactam formation via direct
      annulations of enals and unsaturated N-sulfonyl ketimines.

PMID- 18092786
TI  - A strategy to discover inhibitors of O-linked glycosylation.

PMID- 18092787
TI  - Enzyme-catalyzed synthesis of furanosyl nucleotides.
AB  - A bacterial alpha-d-glucopyranosyl-1-phosphate thymidylyltransferase was found to
      couple four hexofuranosyl-1-phosphates, as well as a pentofuranosyl-1-phosphate,
      with deoxythymidine 5'-triphosphate, providing access to furanosyl nucleotides.
      The enzymatic reaction mixtures were analyzed by electrospray ionization mass
      spectrometry and NMR spectroscopy to determine the anomeric stereochemistry of
      furanosyl nucleotide products. This is the first demonstration of a
      nucleotidylyltransferase discriminating between diastereomeric mixtures of sugar
      1-phosphates to produce stereopure, biologically relevant furanosyl nucleotides.

PMID- 18092788
TI  - Total synthesis of (+/-)-stemonamide and (+/-)-isostemonamide using a radical
      cascade.
AB  - Total synthesis of stemonamide and isostemonamide is described. The concise
      construction of the tricyclic core of these alkaloids was achieved by radical
      cascade involving 7-endo and 5-endo cyclizations.

PMID- 18092789
TI  - Asymmetric synthesis of C2-symmetric vicinal diamines via reductive dimerization
      of N-acylpyridinium and related salts.
AB  - A new route to C2-symmetric diamines via an asymmetric reductive dimerization of
      1-acylpyridinium salts and their benzo derivatives is described. This method is
      practical as the starting heterocycles and chiral auxiliaries are readily
      available. The titanium reducing agent is inexpensive and easy to prepare.
      Several novel enantiopure C2-symmetric diamine derivatives were synthesized using
      this method.

PMID- 18092791
TI  - A computational study of the formation and dimerization of benzothiet-2-one.
AB  - A computational B3LYP/6-31G(d,p) study of the formation of benzothiet-2-one (4)
      from benzothiophenedione (2) and its subsequent dimerization to 5 was performed.
      The proposed intermediate ketene 3 has no gas-phase barrier to ring closure to 4.
      Three transition structures for dimerization were located. The geometry of the
      lowest energy one (TS8a) has a geometry corresponding to a two atom + two atom,
      face-to-face addition of the two thiolactone moieties. The orbital interactions
      suggest that the reaction is pseudopericyclic.

PMID- 18092790
TI  - Electron-deficient dienes. 5. An inverse-electron-demand Diels-Alder approach to
      2-substituted 4-methoxyxanthones and 3,4-dimethoxyxanthones.
AB  - Several 4-methoxyxanthones and 3,4-dimethoxyxanthones were synthesized in good
      yield via inverse-electron-demand Diels-Alder (IEDDA) driven domino reactions
      between a series of electron-deficient chromone-fused dienes with 1-(2,2
      dimethoxyvinyl)pyrrolidine or tetramethoxyethene, respectively.

PMID- 18092792
TI  - Carbazole-based donor-acceptor compounds: highly fluorescent organic
      nanoparticles.
AB  - Carbazole-based donor-acceptor compounds 1,2-dicyano-trans-1,2-bis-4
      (carbazolyl)phenylethylene (1) and 1,2-dicyano-trans-1,2-bis-4-(3,6-di-tert
      butylcarbazolyl)phenylethylene (2) were synthesized. 1 and 2 show negative
      solvatochromic absorption behavior, but show both positive and negative
      solvatochromic behavior in the fluorescence spectra. In a water/THF mixture, 1 as
      well as 2 aggregate into 50-150 nm nanoparticles. The emission of nanoparticles
      of the new types of fluorescent organic nanoparticles (FONs) 1 and 2 is much
      higher than that of either 1 or 2 in solution.

PMID- 18092793
TI  - (BDP)CuH: a "hot" Stryker's reagent for use in achiral conjugate reductions.
AB  - A ligand-modified, economical version of Stryker's reagent (SR) has been
      developed based on a bidentate, achiral bis-phosphine. Generated in situ,
      "(BDP)CuH" smoothly effects conjugate reductions of a variety of unsaturated
      substrates, including those that are normally unreactive toward SR. Substrate-to
      ligand ratios typically on the order of 1000-10000:1 can be used leading to
      products in high yields.

PMID- 18092794
TI  - A terphenyl scaffold for pi-stacked guanidinium recognition elements.
AB  - A new synthetic model of arginine-carboxylate-aromatic triads-common motifs at
      sites of protein-protein interactions-is reported. Binding studies in mixed
      methanol/water solvent systems suggest that the carboxylate-binding ability of pi
      stacked guanidinium ions is improved relative to a non-stacked control.

PMID- 18092795
TI  - Mild amidation of aldehydes with amines mediated by lanthanide catalysts.
AB  - Catalytic amidation of aldehydes with amines is efficiently mediated by
      homoleptic lanthanide amido complexes, Ln[N(SiMe3)2]3 (Ln = La, Sm, and Y).
      Amidation reactivity follows the trend: La > Sm approximately Y. These reactions
      proceed in high yield without added oxidants, bases, and/or heat or light, which
      are usually required in other catalytic amidation processes. The reaction is
      demonstrated with a variety of amines, with yields as high as 98% based on amine.

PMID- 18092796
TI  - Rhodium-catalyzed one-pot synthesis of substituted pyridine derivatives from
      alpha,beta-unsaturated ketoximes and alkynes.
AB  - A rhodium-catalyzed chelation-assisted C-H activation of alpha,beta-unsaturated
      ketoximes and the reaction with alkynes to afford highly substituted pyridine
      derivatives is described.

PMID- 18092797
TI  - Enantiomerically pure alpha-amino aldehydes from silylated alpha-amino acids.
AB  - The disilylation of alpha-amino acids 1 to provide 2 (72-87%) was achieved
      without racemization. An unprecedented borane-mediated semi-reduction strategy
      was devised to convert 2 to stable, isolable oxazaborolidines 3 (100%) which were
      hydrolyzed to provide 5 (49-60%) as pure, stable compounds. Analysis of the
      Mosher amides (8) of the gamma-amino esters 7 reveals that < or =2% racemization
      occurs in the 1 --> 8 conversions.

PMID- 18092798
TI  - Acyclic 1,4-stereocontrol via reductive 1,3-transpositions.
AB  - One-pot reduction/allylic diazene rearrangement of lactic acid- and mandelic acid
      derived alpha,beta-unsaturated tosyl hydrazones leads to 1,4-syn- or 1,4-anti-E-2
      alkenyl arrays in high yield and diastereoselectivity. Either the syn or the anti
      diastereomer can be prepared by choosing the appropriate alkene stereoisomer of
      the hydrazone. The E-alkenes led to the 1,4-syn isomers, while the Z-alkenes led
      to the 1,4-anti isomers, both with > or =20:1 diastereoselectivity.

PMID- 18092799
TI  - Limited use of Centritech Lab II Centrifuge in perfusion culture of rCHO cells
      for the production of recombinant antibody.
AB  - Perfusion cultures of recombinant Chinese hamster ovary cells, producing
      recombinant antibody against the S surface antigen of Hepatitis B virus, were
      carried out in continuous and intermittent mode using a Centritech Lab II
      Centrifuge. In the continuous perfusion process, despite the absence of shear
      stress from the pump head, long-term operation was not possible because of
      continuously repeated exposure to oxygen limitation and low temperature, as well
      as shear stress from centrifugal force. In the intermittent perfusion processes,
      the frequency of cell-passage through the centrifuge was substantially reduced,
      compared with the continuous perfusion mode; however, the degree of reduction
      could not guarantee stable long-term operation. Although various operating
      parameters were applied in the intermittent perfusion cultures, high cell
      densities could not be maintained stably. In a single bioreactor culture system,
      a specific cell that is returned from the centrifuge to the bioreactor could be
      transferred from the bioreactor to the centrifuge again in the next cycle. These
      repetitive damages, caused by shear stress from the pump head and centrifugal
      force, as well as exposure to suboptimal conditions such as oxygen limitation and
      low temperature below 37 degrees C, were more serious at higher perfusion rates.
      Subsequently, damaged cells and dead cells were continuously accumulated in the
      bioreactor. Culture temperature shift from 37 to 33 degrees C increased antibody
      concentrations but showed inhibitory effects on cell growth. The negative effects
      of lowering culture temperature on cell growth overwhelmed the positive effects
      on antibody production. To protect cells from shear stress, Pluronic F-68 was 2
      fold concentrated in the culture medium; nevertheless, a significantly higher
      concentration of Pluronic F-68 (2 g/L) may have inhibitory effects on cell
      growth.

PMID- 18092800
TI  - Production of the apoptotic cellular mediator 4-Methylthio-2-oxobutyric acid by
      using an enzymatic stirred tank reactor with in situ product removal.
AB  - d-Amino acid oxidase (DAAO) was used to study the oxidative deamination of
      racemic mixtures of d,l-methionine in its soluble and immobilized forms and thus
      obtain the corresponding alpha-keto acid. The soluble enzyme form was obtained
      from a Trigonopsis variabilis CBS 4095 extract, free of l-amino acid oxidase, and
      was co-immobilized with a 200-fold excess of catalase to avoid the undesirable
      side reaction of H2O2 with the alpha-keto acid, which would otherwise render its
      corresponding decarboxylated acid, the 3-methylthiopropionic acid (MTPA). With
      this biocatalyst, quantitative conversion (>98%) of d-methionine into the alpha
      keto acid 4-methylthio-2-oxobutyric acid (MTOB) and into MTPA was achieved using
      5 mg.mL(-1) of biocatalyst at pH 8.0, 25 degrees C, and pure oxygen at 3 vvm. A
      stirred tank reactor with in situ product removal (STR-ISPR) was developed to
      avoid conversion of MTOB into MTPA. The reaction medium was re-circulated through
      a strong anion exchange column (Amberlite IRA-400). This resulted in the complete
      removal of MTOB from the reaction medium. After the reaction, the reaction
      products were eluted sequentially with water (l-methionine), 10 mM HCl (MTPA),
      and 0.5 M HCl (MTOB). After elution, MTOB was crystallized to its sodium salt.

PMID- 18092801
TI  - Syntheses of (S,S)-reboxetine via a catalytic stereospecific rearrangement of
      beta-amino alcohols.
AB  - The formal total synthesis of (S,S)-reboxetine has been realized by two different
      approaches using a stereospecific rearrangement of beta-amino alcohols catalyzed
      by (CF3CO)2O.

PMID- 18092802
TI  - Synthesis of epi-oxetin via a serine-derived 2-methyleneoxetane.
AB  - The unique reactivity of 2-methyleneoxetanes and 1,5-dioxaspiro[3.2]hexanes has
      been exploited for the synthesis of epi-oxetin (26), an oxetane-containing beta
      amino acid. While the preparation of the natural product oxetin (1) was the
      original goal, the unexpected diastereoselectivity of an precedented reduction
      provided the epi-oxetin framework. The methodology described herein should be
      amenable for the preparation of oxetin with a change in nitrogen protection.

PMID- 18092803
TI  - Reaction mechanism and stereoselectivity of ruthenium--porphyrin-catalyzed
      intramolecular amidation of sulfamate ester: a DFT computational study.
AB  - The reaction mechanism of the ruthenium--porhyrin complex [Ru(por)(CO)]-catalyzed
      intramolecular C-H bond amidation was examined using density functional theory
      (DFT) calculations. The metal-nitrene reactive intermediate, Ru(por)(CO)-NSO3R1
      (R1 = 1-methylclohexl-methyl) was found to be highly favorable to generate in
      terms of the free energy profile from the reaction of the starting materials.
      Ru(por)(CO)-NSO3R1 may exist in both singlet and triplet states since they are
      close in energy. In each state, six C-H bond amidation reaction pathways were
      characterized structurally and energetically. The predicted most probable
      diastereomeric product out of the four possible diasteromeric products examined
      in the calculations for the amidation reactions agree well with previously
      reported experimental results.

PMID- 18092804
TI  - Chiral N-acyloxazolidines: synthesis, structure, and mechanistic insights.
AB  - A series of chiral imines derived from 1-amino-1-deoxyalditols such as d
      glucamine, a rather unexplored raw material from the chiral pool, have been
      serendipitiously transformed into a novel family of N-acetyl-1,3-oxazolidines by
      means of an unexpected acetylation. The structure of these substances is
      supported by spectroscopic and crystallographic data. The acetylates also trigger
      a complex dynamic transformation, in which an initially configured trans
      oxazolidine converts into a more stable cis-configured derivative. Both isomers
      can also exist as rotational conformers (E,Z) as a consequence of the restricted
      rotation around the N-acetyl bond. The barriers to rotation have been determined
      by variable-temperature experiments. Overall, this transformation most likely
      involves the intermediacy of a chiral iminium ion, which has been documented in
      the synthesis of nitrogen heterocycles, thus explaining the experimental facts.

PMID- 18092805
TI  - Synthesis of caprazamycin analogues and their structure--activity relationship
      for antibacterial activity.
AB  - Synthesis of palmitoyl caprazol 7, which possesses a simple fatty acyl side chain
      at the 3' ''-position of the diazepanone moiety, was carried out and their
      antibacterial activity was evaluated. The key elements of our approach include
      the improved synthesis of the key 5'-beta-O-aminoribosyl-glycyluridine
      derivative, installation of the palmitoyl side chain to the cyclization
      precursor, and the construction of the diazepanone by an intramolecular reductive
      amination. The second generation synthesis of (+)-caprazol was also established.
      Palmitoyl caprazol 7 exhibited antibacterial activity against Mycobacterium
      smegmatis ATCC607 (MIC = 6.25 microg/mL) with potency similar to that of the
      caprazamycins (CPZs). Palmitoyl caprazol 7 and N6'-desmethyl palmitoyl caprazol
      28 also exhibited antibacterial activity against drug-resistant bacteria
      including methyciline-resistant Staphylococcus aureus (MRSA) and vancomycin
      resistant Enterococcus (VRE) strains (MIC = 3.13-12.5 microg/mL).

PMID- 18092806
TI  - Nile Red is a fluorescent allosteric substrate of cytochrome P450 3A4.
AB  - Cytochrome P450 3A4 (CYP3A4) plays a critical role in the metabolism of many
      drugs. CYP3A4 exhibits extraordinary substrate promiscuity and unusual allosteric
      kinetics. In addition, many CYPs catalyze sequential oxidations on a single
      substrate, but in most cases, mechanistic details of these processes are not well
      established. As a result, in vivo clearance of many drugs and their metabolites
      is difficult to predict on the basis of the complex in vitro kinetics, and new in
      vitro probes are required to understand these behaviors. The near-IR fluorescent
      probe Nile Red, which has strong solvatochromic behavior, was investigated as a
      probe of allostery and sequential metabolism with CYP3A4. Nile Red binds with
      apparent Kd values of 0.05 and 2.3 muM, based on a sigmoidal dependence of heme
      spin state on Nile Red concentration, where the first equivalent of Nile Red
      increased the high-spin fraction by only 13% of the total change at saturation.
      Mass spectrometry analysis indicates that Nile Red is metabolized sequentially by
      CYP3A4 to the N-monoethyl and N-desethyl products, confirming that the immediate
      vicinity of the heme iron is one binding site. In the presence of CYP3A4, steady
      state fluorescence emission and excitation spectra, as well as excited-state
      lifetimes at varying Nile Red concentrations, indicate a high-affinity site that
      modulates the fluorescent properties of Nile Red. The Nile Red binding site is
      competitively eliminated by itraconazole, which is a high-affinity ligand known
      to coordinate to the heme iron. Together, the data suggest that Nile Red binds to
      the active site with high affinity ( approximately 50 nM), where it is desolvated
      in a low-dielectric environment. In addition, Nile Red is sequentially oxidized
      at rates comparable to or faster than those of other in vitro probes, which
      emphasizes its utility in the further examination of this important kinetic
      phenomenon in vitro.

PMID- 18092807
TI  - Dual function of RNase E for control of M1 RNA biosynthesis in Escherichia coli.
AB  - M1 RNA, the gene product of rnpB, is the catalytic subunit of RNase P in
      Escherichia coli. M1 RNA is transcribed from a proximal promoter as pM1 RNA, a
      precursor M1 RNA, and then is processed at its 3' end by RNase E. In addition to
      pM1 RNA, large rnpB-containing transcripts are produced from unknown upstream
      promoters. However, it is not known yet how these large transcripts contribute to
      M1 RNA biosynthesis. To examine their biological relevance to M1 RNA
      biosynthesis, we constructed a model upstream transcript, upRNA, and analyzed its
      cellular metabolism. We found that upRNA was primarily degraded rather than
      processed to M1 RNA in the cell and that this degradation occurred in RNase E
      dependent manner. The in vitro cleavage assay with the N-terminal catalytic
      fraction of RNase E showed that the M1 RNA structural sequence in upRNA was much
      more vulnerable to the enzyme than the sequence in pM1 RNA. Considering that
      RNase E is a processing enzyme involved in 3' end formation of M1 RNA, our
      results imply that this enzyme plays a dual role in processing and degradation to
      achieve tight control of M1 RNA biosynthesis.

PMID- 18092808
TI  - Mutational analysis of the active site flap (20s loop) of mandelate racemase.
AB  - Mandelate racemase from Pseudomonas putida catalyzes the Mg2+-dependent 1,1
      proton transfer that interconverts the enantiomers of mandelate. Residues of the
      20s and 50s loops determine, in part, the topology and polarity of the active
      site and hence the substrate specificity. Previously, we proposed that, during
      racemization, the phenyl ring of mandelate moves between an S-pocket comprised of
      residues from the 50s loop and an R-pocket comprised of residues from the 20s
      loop [Siddiqi, F., Bourque, J. R., Jiang, H., Gardner, M., St. Maurice, M.,
      Blouin, C., and Bearne, S. L. (2005) Biochemistry 44, 9013-9021]. The 20s loop
      constitutes a mobile beta-meander flap that covers the active site cavity
      shielding it from solvent and controlling entry and egress of ligands. To
      understand the role of the 20s loop in catalysis and substrate specificity, we
      constructed a series of mutants (V22A, V22I, V22F, T24S, A25V, V26A, V26L, V26F,
      V29A, V29L, V29F, V26A/V29L, and V22I/V29L) in which the sizes of hydrophobic
      side chains of the loop residues were varied. Catalytic efficiencies (kcat/Km)
      for all mutants were reduced between 6- and 40-fold with the exception of those
      of V22I, V26A, V29L, and V22I/V29L which had near wild-type efficiencies with
      mandelate. Thr 24 and Ala 25, located at the tip of the 20s loop, were
      particularly sensitive to minor alterations in the size of their hydrophobic side
      chains; however, most mutations were tolerated quite well, suggesting that flap
      mobility could compensate for increases in the steric bulk of hydrophobic side
      chains. With the exception of V29L, with mandelate as the substrate, and V22F and
      V26A/V29L, with 2-naphthylglycolate (2-NG) as the substrate, the values of kcat
      and Km were not altered in a manner consistent with steric obstruction of the R
      pocket, perhaps due to flap mobility compensating for the increased size of the
      hydrophobic side chains. Surprisingly, V22I and V29L catalyzed the racemization
      of the bulkier substrate 2-NG with kcat/Km values approximately 2-fold greater
      than those observed for wild-type mandelate racemase. Although minor changes in
      substrate specificity were achieved through alterations of the active site flap
      of mandelate racemase, our results suggest that hydrophobic residues that reside
      on a flexible flap and define the topology of an active site through their van
      der Waals contacts with the substrate are quite tolerant of a variety of steric
      substitutions.

PMID- 18092809
TI  - AAV-2 Rep78 and HPV-16 E1 interact in vitro, modulating their ATPase activity.
AB  - Adeno-associated virus (AAV) is a nonpathogenic single-stranded human parvovirus
      which usually requires the presence of a "helper" virus for strong DNA
      replication. In addition to adeno- and herpes viruses, human papillomavirus (HPV)
      can serve as an AAV helper. We recently published that HPV type 16 (HPV-16) E1
      protein contributes significantly as an individual helper gene for AAV-2 DNA
      replication and transcription. As Rep78 and E1 are the corresponding DNA
      helicase/replication proteins of AAV and HPV, respectively, and Rep78 and E1 have
      a degree of homology, we assayed whether these two proteins interact physically.
      The full length proteins were purified from bacteria as GST-E1 and MBP-Rep78 and
      used in five assays to observe Rep78-E1 interactions. All five assays (pull-down,
      coimmunoprecipitation, enzyme-linked immunosorbent assay (ELISA), chemical cross
      linking, and ATPase activity) provided evidence consistent with Rep78-E1
      interaction. Most intriguing, an overall decrease in ATPase activity was observed
      when both proteins were present together. These data strongly suggest that E1 and
      Rep78 interact and that this interaction modulates at least some of their
      individual biochemical functions. This study adds to our understanding of AAV-HPV
      interaction biology, E1's modulation of Rep78 biochemistry, Rep78's modulation of
      E1 biochemistry and provides initial clues which may lead to the underlying
      mechanism of HPV E1 helper function for AAV DNA replication.

PMID- 18092810
TI  - C-Terminal mutations in the chloroplast ATP synthase gamma subunit impair ATP
      synthesis and stimulate ATP hydrolysis.
AB  - Two highly conserved amino acid residues, an arginine and a glutamine, located
      near the C-terminal end of the gamma subunit, form a "catch" by hydrogen bonding
      with residues in an anionic loop on one of the three catalytic beta subunits of
      the bovine mitochondrial F1-ATPase [Abrahams, J. P., Leslie, A. G., Lutter, R.,
      and Walker, J. E. (1994) Nature 370, 621-628]. The catch is considered to play a
      critical role in the binding change mechanism whereby binding of ATP to one
      catalytic site releases the catch and induces a partial rotation of the gamma
      subunit. This role is supported by the observation that mutation of the
      equivalent arginine and glutamine residues in the Escherichia coli F1 gamma
      subunit drastically reduced all ATP-dependent catalytic activities of the enzyme
      [Greene, M. D., and Frasch, W. D. (2003) J. Biol. Chem. 278, 5194-5198]. In this
      study, we show that simultaneous substitution of the equivalent residues in the
      chloroplast F1 gamma subunit, arginine 304 and glutamine 305, with alanine
      decreased the level of proton-coupled ATP synthesis by more than 80%. Both the
      Mg2+-dependent and Ca2+-dependent ATP hydrolysis activities increased by more
      than 3-fold as a result of these mutations; however, the sulfite-stimulated
      activity decreased by more than 60%. The Mg2+-dependent, but not the Ca2+
      dependent, ATPase activity of the double mutant was insensitive to inhibition by
      the phytotoxic inhibitor tentoxin, indicating selective loss of catalytic
      cooperativity in the presence of Mg2+ ions. The results indicate that the catch
      residues are required for efficient proton coupling and for activation of
      multisite catalysis when MgATP is the substrate. The catch is not, however,
      required for CaATP-driven multisite catalysis or, therefore, for rotation of the
      gamma subunit.

PMID- 18092811
TI  - Solutes alter the conformation of the ligand binding loops in outer membrane
      transporters.
AB  - The binding and recognition of ligands by bacterial outer membrane transport
      proteins is mediated in part by interactions made through their extracellular
      loops. Here, site-directed spin labeling (SDSL) and electron paramagnetic
      resonance (EPR) spectroscopy were used to examine the effect of stabilizing
      solutes on the extracellular loops in BtuB, the vitamin B12 transporter, and
      FecA, the ferric citrate transporter. EPR spectra from the extracellular loops of
      FecA and BtuB arise from dynamic backbone segments, and distance measurements
      made by double electron-electron resonance indicate that the second extracellular
      loop in BtuB samples a wide range of conformations. These conformations are
      dramatically restricted upon substrate binding. In addition, the EPR spectra from
      nitroxide labels attached to the extracellular loops in BtuB and FecA are highly
      sensitive to solutes, and at every site examined the motion of the label is
      significantly reduced in the presence of stabilizing osmolytes, such as
      polyethylene glycols. For the second extracellular loop in BtuB, the solute
      induced structural changes are small, but they are sufficient to bring spin
      labeled side chains into tertiary contact with other portions of the protein. The
      spectroscopic changes seen by SDSL suggest that high concentrations of
      stabilizing solutes, such as those used to generate membrane protein crystals,
      result in a more compact and ordered state of the protein than is seen under more
      physiological conditions.

PMID- 18092812
TI  - Crystal structure of a molybdopterin synthase-precursor Z complex: insight into
      its sulfur transfer mechanism and its role in molybdenum cofactor deficiency.
AB  - In almost all biological life forms, molybdenum and tungsten are coordinated by
      molybdopterin (MPT), a tricyclic pyranopterin containing a cis-dithiolene group.
      Together, the metal and the pterin moiety form the redox reactive molybdenum
      cofactor (Moco). Mutations in patients with deficiencies in Moco biosynthesis
      usually occur in the enzymes catalyzing the first and second steps of
      biosynthesis, leading to the formation of precursor Z and MPT, respectively. The
      second step is catalyzed by the heterotetrameric MPT synthase protein consisting
      of two large (MoaE) and two small (MoaD) subunits with the MoaD subunits located
      at opposite ends of a central MoaE dimer. Previous studies have determined that
      the conversion of the sulfur- and metal-free precursor Z to MPT by MPT synthase
      involves the transfer of sulfur atoms from a C-terminal MoaD thiocarboxylate to
      the C-1' and C-2' positions of precursor Z. Here, we present the crystal
      structures of non-thiocarboxylated MPT synthase from Staphylococcus aureus in its
      apo form and in complex with precursor Z. A comparison of the two structures
      reveals conformational changes in a loop that participates in interactions with
      precursor Z. In the complex, precursor Z is bound by strictly conserved residues
      in a pocket at the MoaE dimer interface in close proximity of the C-terminal
      glycine of MoaD. Biochemical evidence indicates that the first dithiolene sulfur
      is added at the C-2' position.

PMID- 18092813
TI  - Recombinant expression and initial characterization of the putative human enteric
      ferric reductase Dcytb.
AB  - Recent studies of mutant mice with compromised ability to absorb dietary iron
      have identified involvement of two integral membrane proteins in the intestinal
      epithelial lining in iron uptake, a divalent metal ion transporter and a ferric
      reductase. The current study concerns the recombinant expression, purification,
      and initial spectroscopic characterization of a recombinant form of the human
      ferric reductase that was expressed and purified as the apoprotein from
      Escherichia coli. Reconstitution of the recombinant protein with
      ferriprotoporphyrin IX produced a red product with Soret (Fe3+, lambdamax 413.5
      nm; Fe2+, lambdamax = 426 nm) and visible absorption maxima indicative of
      bisimidazole axial coordination. This observation was confirmed by electron
      paramagnetic resonance and magnetic circular dichroism spectroscopy. Titration of
      apo-Dcytb with ferriprotoporphyrin IX was consistent with the binding of two heme
      groups to the protein as predicted by the phylogenetic relationship of this
      protein to the cytochrome b561 family. Similar titrations and spectroscopic
      studies of two double variants of Dcytb, each lacking a pair of histidyl residues
      (H50 and H120 or H86 and H159) proposed on the basis of sequence alignment with
      other members of the cytochrome b561 family to provide axial ligands to bound
      heme, indicated that these variants were able to bind just one heme group each.

PMID- 18092814
TI  - Secreted 3-isopropylmalate methyl ester signals invasive growth during amino acid
      starvation in Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae methyltransferase encoded by TMT1 catalyzes the
      AdoMet-dependent monomethylation of 3-isopropylmalate, an intermediate of the
      leucine biosynthetic pathway. The biological significance of methylating 3
      isopropylmalate and the relationship between Tmt1 and the leucine biosynthetic
      pathway is not yet established. We present evidence here showing that methylation
      of 3-isopropylmalate functions to extracellularly signal yeast to grow
      invasively. We show that methyl esterification generates 3-isopropylmalate-1
      methyl ester. We find that the Tmt1 methyltransferase functions independently of
      the biosynthetic pathway but is induced when cells are starved for amino acids;
      the largest induction is observed with the removal of leucine from the media.
      This amino acid starvation stress response is controlled by the transcriptional
      activator Gcn4. After methylation, 3-isopropylmalate methyl ester is secreted
      into the media within 3 h. Thin layer chromatography and gas chromatography mass
      spectroscopy confirm that the intact molecule is secreted. Finally, we show that
      purified 3-isopropylmalate methyl ester can enhance the ability of the haploid
      yeast strain 10560-23C to grow invasively. Our data identifies 3-isopropylmalate
      methyl ester as an autoinductive molecule that provides a signal to yeast to
      switch from vegetative to invasive growth in response to amino acid starvation.

PMID- 18092815
TI  - The contribution of naturally occurring polymorphisms in altering the biochemical
      and structural characteristics of HIV-1 subtype C protease.
AB  - Fourteen subtype B and C protease variants have been engineered in an effort to
      study whether the preexistent baseline polymorphisms, by themselves or in
      combination with drug resistance mutations, differentially alter the biochemical
      and structural features of the subtype C protease when compared with those of
      subtype B protease. The kinetic studies performed in this work showed that the
      preexistent polymorphisms in subtype C protease, by themselves, do not provide
      for a greater level of resistance. Inhibition analysis with eight clinically used
      protease inhibitors revealed that the natural polymorphisms found in subtype C
      protease, in combination with drug resistance mutations, can influence enzymatic
      catalytic efficiency and inhibitor resistance. Structural analyses of the subtype
      C protease bound to nelfinavir and indinavir showed that these inhibitors form
      similar interactions with the residues in the active site of subtype B and C
      proteases. It also revealed that the naturally occurring polymorphisms could
      alter the position of the outer loops of the subtype C protease, especially the
      60's loop.

PMID- 18092816
TI  - A sequence-independent study of the influence of short loop lengths on the
      stability and topology of intramolecular DNA G-quadruplexes.
AB  - G-Rich sequences found within biologically important regions of the genome have
      been shown to form intramolecular G-quadruplexes with varied loop lengths and
      sequences. Many of these quadruplexes will be distinguishable from each other on
      the basis of their thermodynamic stabilities and folded conformations. It has
      been proposed that loop lengths can strongly influence the topology and stability
      of intramolecular G-quadruplexes. Previous studies have been limited to the
      analysis of quadruplex sequences with particular loop sequences, making it
      difficult to make generalizations. Here, we describe an original study that aimed
      to elucidate the effect of loop length on the biophysical properties of G
      quadruplexes in a sequence-independent context. We employed UV melting and
      circular dichroism spectroscopy to examine and compare the properties of 21 DNA
      quadruplex libraries, each comprising partially randomized loop sequences with
      lengths ranging from one to three nucleotides. Our work supports a number of
      general predictions that can be made solely on the basis of loop lengths. In
      particular, the results emphasize the strong influence of single-nucleotide loops
      on quadruplex properties. This study provides a predictive framework that may
      help identify or classify biologically relevant G-quadruplex-forming sequences.

PMID- 18092817
TI  - Equilibrium unfolding of the dimeric SAM domain of MAPKKK Ste11 from the budding
      yeast: role of the interfacial residues in structural stability and binding.
AB  - The sterile alpha motifs or SAM domains are small ( approximately 70 amino acids)
      protein-protein interaction modules that are involved in diverse functions
      ranging from cell signaling, transcription regulation, and scaffolding. The Ste11
      protein kinase in the mitogen-activated protein kinase (MAPK) signaling cascades
      of the budding yeast is regulated by a SAM domain located at the N-terminus of
      the full-length protein. The Ste11 SAM domain forms a symmetrical dimeric
      structure with an interface stabilized presumably by hydrophobic and ionic
      interactions. Here, we investigated urea-induced unfolding, using NMR and other
      optical spectroscopic methods, of the dimeric Ste11 SAM domain and two of the
      variants, namely, L57R and L60R, each containing a point mutation at the
      interfacial region. Our results demonstrate that the residue-specific or global
      unfolding of the Ste11 SAM is highly cooperative without any evidence for folded
      monomeric or partially folded species. However, replacement of hydrophobic
      residues with basic residues in the interface caused considerable changes in the
      stability and folding of the Ste11 SAM domain. The native dimeric structure of
      the L60R mutant protein is severely affected as indicated by a high propensity
      toward aggregation. On the other hand, the L57R mutant, although retaining the
      native structure, shows a dramatic decrease in the conformational stability as
      revealed by urea-induced denaturation and amide proton exchange studies.
      Furthermore, isothermal titration calorimetry and intrinsic tryptophan
      fluorescence experiments demonstrate that the L57R interacts with the cognate SAM
      domain from Ste50 with reduced affinity, while the L60R protein is devoid of any
      detectable binding activity. These results demonstrate that the interfacial
      residues of the dimeric SAM domain of Ste11 are critically involved in its
      structural stability and binding to the Ste50 SAM domain.

PMID- 18092818
TI  - Comparison of the structural properties of the active site cavities of human and
      rat monoamine oxidase A and B in their soluble and membrane-bound forms.
AB  - Structural properties of the active site cavities in human and rat monoamine
      oxidases (MAOA and MAOB) have been studied in their detergent-purified and outer
      mitochondrial membrane (OMM) bound forms using a spin-labeled irreversible
      inhibitor (ParSL) as an active specific spin probe. ParSL has been found to be 5
      10-fold more specific for human MAOB (hMAOB) with a Ki of ca. 20 muM, compared to
      Ki's in the range of 100-200 muM observed for other human and rat MAOs. Solvent
      accessibilities of the active-site-bound spin probes have been determined by
      studying the power saturation properties of the spin probe EPR signals in the
      presence and absence of a polar paramagnetic reagent NiEDDA and by measuring the
      extent of spin probe reductions on treatment with excess ascorbic acid. Results
      presented here show that the spin probe bound to the hMAOA active site is ca. 7-8
      fold more accessible than in hMAOB. In contrast, the spin probes covalently
      attached to the two rat enzyme active sites show comparable accessibilities to
      each other. On comparison of human versus rat enzymes, the active-site-bound spin
      probes in the two rat MAOs show ca. 40% less accessibilities compared to the same
      in hMAOA but ca. 4-5-fold higher accessibilities than in hMAOB active site. The
      present data thus suggests that the structural properties of the active site
      cavities in rat MAOs are significantly different compared to those in the two
      human enzymes, which correlates with the differences reported earlier in the
      inhibitor specificities between human and rat MAOs.

PMID- 18092819
TI  - Identification of a novel antiapoptotic human protein kinase C delta isoform,
      PKCdeltaVIII in NT2 cells.
AB  - Protein kinase C (PKC) delta plays an important role in cellular proliferation
      and apoptosis where it is involved in the caspase-3 mediated apoptotic pathway.
      Cleavage of PKCdeltaI by caspase-3 releases a catalytically active C-terminal
      fragment that is sufficient to induce apoptosis. In this paper, we identified a
      novel human PKCdelta isozyme, PKCdeltaVIII (Genbank accession number DQ516383) in
      human teratocarcinoma (NT2) cells that differentiate into hNT neurons upon
      retinoic acid (RA) treatment. Expression of PKCdeltaVIII was confirmed by real
      time RT-PCR analysis, and we observed that after an initial peak at 24 h
      following RA treatment, its expression gradually declined with prolonged RA
      treatment. PKCdeltaVIII is generated via the utilization of an alternative 5'
      splice site, and this results in an insertion of 31 amino acids in the caspase-3
      recognition sequence DMQD. The function of PKCdeltaVIII was examined by
      subcloning it into an expression vector and raising an antibody specific to
      PKCdeltaVIII. Using in vivo and in vitro assays, we demonstrated that
      PKCdeltaVIII is resistant to caspase-3 cleavage. Next, we sought to determine the
      role of PKCdeltaVIII in apoptosis in NT2 cells. Overexpression of PKCdeltaVIII
      and knockdown using PKCdeltaVIII siRNA suggest an antiapoptotic function for the
      PKCdeltaVIII isozyme. We demonstrate that antisense oligonucleotides (ASO)
      directed toward the 5' splice site I promote the expression of the PKCdeltaVIII
      isozyme. Our results indicated that ASO mediated PKCdeltaVIII expression rescued
      NT2 cells from etoposide-induced apoptosis. We conclude that the novel human
      PKCdeltaVIII splice variant functions as an antiapoptotic protein in NT2 cells.

PMID- 18092820
TI  - Dynein light chain LC8 is a dimerization hub essential in diverse protein
      networks.
AB  - The operations within a living cell depend on the collective activity of networks
      of proteins, sometimes termed "interactomes". Within these networks, most
      proteins interact with few partners, while a small proportion of proteins, called
      hubs, participate in a large number of interactions and play a central role in
      organizing these interactomes. LC8 was first discovered as an essential component
      of the microtubule-based molecular motor dynein and as such is involved in
      fundamental processes, including retrograde vesicular trafficking,
      ciliary/flagellar motility, and cell division. More recently, evidence has
      accumulated that LC8 also interacts with proteins that are not clearly connected
      with dynein or microtubule-based transport, including some with roles in
      apoptosis, viral pathogenesis, enzyme regulation, and kidney development. Here,
      we introduce the idea that LC8 is a hub protein essential in diverse protein
      networks, and its function as a dynein light chain is but one of many. We further
      propose that the crucial regulatory roles of LC8 in various systems are due to
      its ability to promote dimerization of partially disordered proteins.

PMID- 18092821
TI  - Recognition of heptoses and the inner core of bacterial lipopolysaccharides by
      surfactant protein d.
AB  - Lipopolysaccharides (LPS) of Gram-negative bacteria are important mediators of
      bacterial virulence that can elicit potent endotoxic effects. Surfactant protein
      D (SP-D) shows specific interactions with LPS, both in vitro and in vivo. These
      interactions involve binding of the carbohydrate recognition domain (CRD) to LPS
      oligosaccharides (OS); however, little is known about the mechanisms of LPS
      recognition. Recombinant neck+CRDs (NCRDs) provide an opportunity to directly
      correlate binding interactions with a crystallographic analysis of the binding
      mechanism. In these studies, we examined the interactions of wild-type and mutant
      trimeric NCRDs with rough LPS (R-LPS). Although rat NCRDs bound more efficiently
      than human NCRDs to Escherichia coli J-5 LPS, both proteins exhibited efficient
      binding to solid-phase Rd2-LPS and to Rd2-LPS aggregates presented in the
      solution phase. Involvement of residues flanking calcium at the sugar binding
      site was demonstrated by reciprocal exchange of lysine and arginine at position
      343 of rat and human CRDs. The lectin activity of hNCRDs was inhibited by
      specific heptoses, including l-glycero-alpha-d-manno-heptose (l,d-heptose), but
      not by 3-deoxy-alpha-d-manno-oct-2-ulosonic acid (Kdo). Crystallographic analysis
      of the hNCRD demonstrated a novel binding orientation for l,d-heptose, involving
      the hydroxyl groups of the side chain. Similar binding was observed for a
      synthetic alpha1-->3-linked heptose disaccharide corresponding to heptoses I and
      II of the inner core region in many LPS. 7-O-Carbamoyl-l,d-heptose and d-glycero
      alpha-d-manno-heptose were bound via ring hydroxyl groups. Interactions with the
      side chain of inner core heptoses provide a potential mechanism for the
      recognition of diverse types of LPS by SP-D.

PMID- 18092822
TI  - Tryptophan mutants of cardiac troponin C: 3D structure, troponin I affinity, and
      in situ activity.
AB  - In situ fluorescence/NMR spectroscopic approaches have been used to elucidate the
      structure, mobility, and domain orientations of troponin C in striated muscle.
      This led us to consider complementary approaches such as solid-state NMR
      spectroscopy. The biophysical properties of tryptophan and Trp-analogues, such as
      fluorotryptophan or hydroxytryptophan, are often exploited to probe protein
      structure and dynamics using solid-state NMR or fluorescence spectroscopy. We
      have characterized Phe-to-Trp mutants in the 'structural' C-domain of cardiac
      troponin C, designed to immobilize the indole ring in the hydrophobic core of the
      domain. The mutations and their fluorinated analogues (F104W, F104(5fW), F153W,
      and F153(5fW)) were shown not to perturb the structural properties of the
      protein. In this paper, we characterize the mutations F77W and F77W-V82A in the
      'regulatory' N-domain of cardiac troponin C. We used NMR to determine the
      structure and dynamics of the mutant F77W-V82A-cNTnC, which shows a unique
      orientation of the indole ring. We observed a decrease in calcium binding
      affinity and a weaker affinity for the switch region of TnI for both mutants. We
      present force recovery measurements for all of the N- and C-domain mutants
      reconstituted into skeletal muscle fibers. The F77W mutation leads to a reduction
      of the in situ force recovery, whereas the C-domain mutants have the same
      activity as the wild type. These results suggest that the perturbations of the N
      domain caused by the Trp mutation disturb the interaction between TnC and TnI,
      which in turn diminishes the activity in fibers, providing a clear example of the
      correlation between in vitro protein structures, their interactions, and the
      resulting in situ physiological activity.

PMID- 18092825
TI  - Photopatterned surfaces for site-specific and functional immobilization of
      proteins.
AB  - Photosensitive silanes containing nitroveratryl (Nvoc)-caged amine groups and
      protein repellent tetraethylene glycol units were synthesized and used for
      modification of silica surfaces. Functional surface layers containing different
      densities of caged amine groups were prepared and activated by UV-irradiation of
      the surface. The performance of these layers for functional and site-selective
      immobilization of proteins was tested. For this purpose, biotin and tris
      nitrilotriacetic acid (tris-NTA) were fist coupled to the activated surface, and
      the interaction of streptavidin and His-tagged proteins with the functionalized
      surfaces was monitored by real-time label-free detection. After optimizing the
      coupling protocols, highly selective functionalization of the deprotected amine
      groups was possible. Furthermore, the degree of functionalization (and therefore
      the amount of immobilized protein) was controlled by diluting the surface
      concentration of the amine-functionalized silane with a nonreactive (OMe
      terminated) tetraethylene glycol silane. Immobilized proteins were highly
      functional on these surfaces, as demonstrated by protein-protein interaction
      assays with the type I interferon receptor. Protein micropatterns were
      successfully generated after masked irradiation and functionalization of the
      caged surface following the optimized coupling protocols.

PMID- 18092823
TI  - Phosphorylation of paxillin LD4 destabilizes helix formation and inhibits binding
      to focal adhesion kinase.
AB  - Cell migration is a dynamic process that requires the coordinated formation and
      disassembly of focal adhesions (FAs). Several proteins such as paxillin, focal
      adhesion kinase (FAK), and G protein-coupled receptor kinase-interacting protein
      1 (GIT1) are known to play a regulatory role in FA disassembly and turnover.
      However, the mechanisms by which this occurs remain to be elucidated. Paxillin
      has been shown to bind the C-terminal domain of FAK in FAs, and an increasing
      number of studies have linked paxillin association with GIT1 during focal
      adhesion disassembly. It has been reported recently that phosphorylation of
      serine 273 in the LD4 motif of paxillin leads to an increased association with
      Git1 and focal adhesion turnover. In the present study, we examined the effects
      of phosphorylation of the LD4 peptide on its binding affinity to the C-terminal
      domain of FAK. We show that phosphorylation of LD4 results in a reduction of
      binding affinity to FAK. This reduction in binding affinity is not due to the
      introduction of electrostatic repulsion or steric effects but rather by a
      destabilization of the helical propensity of the LD4 motif. These results further
      our understanding of the focal adhesion turnover mechanism as well as identify a
      novel process by which phosphorylation can modulate intracellular signaling.

PMID- 18092826
TI  - Growth of straight, atomically perfect, highly metallic silicon nanowires with
      chiral asymmetry.
AB  - In the quest of nano-objects for future electronics, silicon nanowires could
      possibly take over carbon nanotubes. Here we show the growth by self-organization
      of straight, massively parallel silicon nanowires having a width of 1.6 nm, which
      are atomically perfect and highly metallic conductors. Surprisingly, these
      silicon nanowires display a strong symmetry breaking across their widths with two
      chiral species that self-assemble in large left-handed and right-handed magnetic
      like domains.

PMID- 18092827
TI  - Biological implications of isochore boundaries in the human genome.
AB  - The human genome is composed of large sequence segments with fairly homogeneous
      GC content, namely isochores, which have been linked to many important functions;
      biological implications of most isochore boundaries, however, remain elusive,
      partly due to the difficulty in determining these boundaries at high resolution.
      Using the segmentation algorithm based on the quadratic divergence, we re
      determined all 79 boundaries of previously identified human isochores at single
      nucleotide resolution, and then compared the boundary coordinates with other
      genome features. We found that 55.7% of isochore boundaries coincide with termini
      of repeat elements; 45.6% of isochore boundaries coincide with termini of highly
      conserved sequences based on alignment of 17 vertebrate genomes, i.e., the highly
      conserved genome sequence switches to a less or non-conserved one at the isochore
      boundary; some isochore boundaries coincide with abrupt change of CpG island
      distribution (note that one boundary can associate with more than one genome
      feature). In addition, sequences around isochore boundaries are highly conserved.
      It seems reasonable to deduce that the boundaries of all the isochores studied
      here would be replication timing sites in the human genome. These results suggest
      possible key roles of the isochore boundaries and may further our understanding
      of the human genome organization.

PMID- 18092828
TI  - The longest (A+T) and (G+C) blocks in the human and other genomes.
AB  - We analysed complete or almost complete nucleotide sequences of the human, chimp,
      mouse, rat, chicken, dog, and other genomes to find that they contain extremely
      long (A+T) a (G+C) blocks that do not occur at all in the corresponding
      randomized sequences. The longest is an (A+T) block containing 1040 consecutive
      AT pairs that occurs in the 16th human chromosome. The longest human (G+C) block
      has 261 bp in length. About a half of the longest blocks occur in introns. The
      (A+T) blocks are discrete units whereas the (G+C) blocks are diffuse. They are
      imbedded in the genome through connectors longer than 1 kilobase where the (G+C)
      content gradually decreases to the value of 50%. Remarkably, the (A+T) as well as
      (G+C) blocks are substantially shorter in the chimp genome. Chicken is
      characteristic by very long (G+C) blocks that are even longer than in the human
      genome. Though much shorter, long (G+C) and especially (A+T) blocks occur in
      lower organisms as well, which means that AT and GC pair clustering is an ancient
      property that has evolved into large scales in higher eukaryote genomes and the
      human genome in particular. Very long (A+T) and (G+C) blocks confer specific
      biophysical properties on DNA that are likely to influence genome folding in cell
      nuclei and its functional properties.

PMID- 18092829
TI  - Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and
      molecular interaction field studies to design novel potential MAO-B inhibitors.
AB  - Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of
      the cells, which is responsible for the oxidative deamination of neurotransmitter
      and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO
      B, each displaying different substrate and inhibitor specificities. They are the
      well-known targets for antidepressant, Parkinson's disease, and neuroprotective
      drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened
      the way for the molecular modeling studies. In this work we have used molecular
      modeling, density functional theory with correlation, virtual screening, flexible
      docking, molecular dynamics, ADMET predictions, and molecular interaction field
      studies in order to design new molecules with potential higher selectivity and
      enzymatic inhibitory activity over MAO-B.

PMID- 18092830
TI  - Three-dimensional models of NB-ARC domains of disease resistance proteins in
      tomato, Arabidopsis, and flax.
AB  - Three dimensional models of NB-ARC domains in five different proteins were
      constructed based on the recently published crystal structure of the apoptotic
      protease activating factor 1, of which two are for tomato species, one each for
      flax, Arabidopsis, and nematode. Standard multiple sequence alignment was
      performed for chosen members of the NB-ARC domains, very divergent from each
      other in protein sequence, followed by homology model building and structure
      refinement. In this alignment, amino acid insertions and deletions between
      members generally fall in loop regions or at ends of alpha helices. Despite the
      presence of sequence divergence between the species, it is argued that the NB-ARC
      domains carry out the similar biological functions in the various species,
      highlighting the ATP binding and ATPase activity. By our comparative study of
      these models, it is predicted that NB-ARC domains should bind ADP/ATP rather than
      GDP/GTP. Both natural and induced mutants of Arabidopsis within the RPS2 locus
      and their phenotypes for disease reaction against Pseudomonas syringae are
      rationalized from the protein model. Apaf-1 Thr263 and Arg265 positions conserved
      totally within the NB-ARC domains are predicted to take active part in the
      catalytic activity of kinase-3 motif, the arginine known as the sensor I motif in
      AAA+ proteins. This was later verified for the Ced-4 crystal structure in complex
      with Ced-9. Our model of Ced-4 based on Apaf-1 was also compared with its crystal
      structure in the Ced-4-Ced-9 complex; the 3 layered alpha/beta domain superposes
      quite well, helical domain I is shifted by about 5 A but the winged helix domain
      is rotated away to a new position. Since Apaf-1 was crystallized with ADP and Ced
      4-Ced9 with magnesium-ATP, this rotation signifies a change in structure of these
      NB-ARC domains between the two forms. Further, we hypothesize that certain
      mutants in the plant R proteins called 'constitutive gain-of-function' or
      'autocatalytic' dispose their winged helix domains permanently like the magnesium
      ATP form as observed for Ced-4, avoiding the closed ADP conformation. The models
      are also validated with mutagenesis data for a related tomato protein I-2, tomato
      prf and flax, including loss of function, wild type and autocatalytic phenotypes,
      and compared with similar data for potato and tobacco proteins, for which models
      were not built. These three dimensional models would help us to understand the
      spatial arrangement, function of R proteins and their conserved motifs.

PMID- 18092831
TI  - Homology modeling of wild-type, D516V, and H526L Mycobacterium tuberculosis RNA
      polymerase and their molecular docking study with inhibitors.
AB  - Rifamicyns (Rifs) are antibiotic widely used for the treatment of tuberculosis
      (TB); nevertheless, their efficacy has been limited by a high percentage of
      mutations, principally in the rpoB gene. In this work, the first three
      dimensional molecular model of the hypothetical structures for the wild-type and
      D516V and H526L mutants of Mycobacterium tuberculosis (mtRNAP) were elucidated by
      a homology modeling method. In addition, the orientations and binding affinities
      of some Rifs with those new structures were investigated. Our findings could be
      helpful for the design of new more potent rifamycin analogs.

PMID- 18092832
TI  - Binding mode analysis of 2,4-diamino-5-methyl-5-deaza-6-substituted pteridines
      with Mycobacterium tuberculosis and human dihydrofolate reductases.
AB  - There are major differences between the structures of human dihydrofolate
      reductase (hDHFR) and Mycobacterium tuberculosis dihydrofolate reductase
      (mtDHFR). These differences may allow the design of more selective mtDHFR
      inhibitors. In this paper, we have used docking approaches to study the binding
      orientations and predict binding affinities of 2,4-diamino-5-methyl-5
      deazapteridines derivatives in both hDHFR and mtDHFR. Our results of molecular
      docking combined with experimental data for inhibition of the human and
      mycobacterial dihydrofolate reductases suggest the presence of empty spaces
      around the 2,4-diaminodeazapteridine and N10-phenyl rings in the mtDHFR active
      site that are not found in the hDHFR-bound structures. Preparation of new analogs
      with substituents attached to C7 of the pteridine nucleus and positions 3 and 4
      of the N10-phenyl group should increase the affinity and selectivity for mtDHFR.

PMID- 18092833
TI  - Protein unfolding in drug-RNase complexes.
AB  - Bovine pancreatic ribonuclease A (RNase A) catalyzes the cleavage of P-O5' bonds
      in RNA on the 3' side of pyrimidine to form cyclic 2', 5'-phosphates. It has
      several high affinity binding sites that make it possible target for many organic
      and inorganic molecules. Ligand binding to RNase A can alter protein secondary
      structure and its catalytic activity. In this review, the effects of several
      drugs such as AZT (anti-AIDS), cis-Pt (antitumor), aspirin (anti-inflammatory),
      and vitamin C (antioxidant) on the stability and conformation of RNase A in vitro
      are compared. The results of UV-visible, FTIR, and CD spectroscopic analysis of
      RNase complexes with aspirin, AZT, cis-Pt, and vitamin C at physiological
      conditions are discussed here. Spectroscopic results showed one major binding for
      each drug-RNase adduct with KAZT=5.29 (+/-1.6)x10(4) M(-1), Kaspirin=3.57 (+/
      1.4)x10(4) M(-1), Kcis-Pt=5.66 (+/-1.9)x10(3) M(-1), and Kascorbate=3.50 (+/
      1.5)x10(3) M(-1). Major protein unfolding occurred with reduction of alpha-helix
      from 29% (free protein) to 20% and increase of beta-sheet from 39% (free protein)
      to 45% in the aspirin-, ascorbate-, and cis-Pt-RNase complexes, while minor
      increase of alpha-helix was observed for AZT-RNase adduct.

PMID- 18092834
TI  - Structural characterization of neurokinin-3 receptor selective peptide agonist
      scyliorhinin II bound to DPC micelles.
AB  - Scyliorhinin II, a cyclic Tachykinin peptide, is a potent NK3 receptor agonist.
      The pharmacology of NK3 receptor is least characterized out of the three
      tachykinin receptor subtypes cloned and characterized for Tachykinins. To
      understand the structural basis of peptide-receptor interaction, the three
      dimensional structure of the Scyliorhinin II in aqueous and micellar environments
      has been studied by two-dimensional proton nuclear magnetic resonance (2D 1H-NMR
      spectroscopy) and distance geometry calculations. Proton NMR assignments have
      been carried out with the aid of correlation spectroscopy (gradient-COSY and
      TOCSY) and nuclear Overhauser effect spectroscopy (NOESY and ROESY) experiments.
      The inter proton distances and dihedral angle constraints obtained from the NMR
      data have been used in torsion angle dynamics algorithm for NMR applications
      (DYANA) to generate a family of structures, which have been refined using
      restrained energy minimization and dynamics. The results show that in an aqueous
      environment, Scyliorhinin II lacks a definite secondary structure. The structure
      is well-defined in presence of dodecyl phosphocholine micelles. The global fold
      of Scyliorhinin II bound to DPC micelles consists of a well-defined helix in the
      C-terminal region from residue 12-18 and a series of turns towards N-terminus.
      The structure is further stabilized by disulfide bond between Cys7 and Cys13. The
      conformational range of the peptide revealed by NMR and CD studies has been
      analyzed in terms of characteristic secondary features. Observed conformational
      features have been compared with those of Substance P, Neurokinin A and
      Neurokinin B, potent NK1, NK2, and NK3 agonists, respectively.

PMID- 18092835
TI  - Compensation of DNA stabilization and destabilization effects caused by cisplatin
      is partially disturbed in alkaline medium.
AB  - Binding of the antitumor compound cisplatin to DNA locally distorts the double
      helix. These distortions correlate with a decrease in DNA melting temperature
      (Tm). However, the influence of cisplatin on DNA stability is more complex
      because it decreases the DNA charge density. In this way, cisplatin increases the
      melting temperature and partially compensates for the destabilizing influence of
      structural distortions. The stabilization is stronger at low Na+ ion
      concentration. Due to this compensation, the total decrease in the DNA melting
      temperature after cisplatin binding is much lower than the decrease caused by the
      distortions themselves, especially at low [Na+]. It is shown in this study that,
      besides Na+ concentration, pH also strongly influences the value of a change in
      the melting temperature caused by cisplatin. In alkaline medium (pH=10.5-10.8), a
      fall in the melting temperature caused by platination is enhanced several times
      with respect to neutral medium. Such a stronger drop in Tm is explained by a
      decrease in pK values of base pairs caused by lowering the charge density under
      platination that facilitates proton release. At neutral pH, the proton release is
      low for both control and platinated DNA and does not influence the melting
      behavior. Therefore, lowering in the charge density under platination, besides
      stabilization, gives additional destabilization just in alkaline medium.
      Destabilization caused by structural distortions due to this pH induced
      compensation of stabilizing effect is more pronounced. In the presence of
      carbonate ion, destabilization caused by high pH value is strengthened. As a
      decrease in DNA charge density, interstrand crosslinking caused by cisplatin also
      increases the DNA stability due to loss in the entropy of the melted state.
      However, computer modeling of DNA stability demonstrates that interstrand
      crosslinks formed by cisplatin do not stabilize long DNA. It is shown that the
      increase in Tm caused by interstrand crosslinking itself is compensated for by a
      local destabilization of the double helix at the sites of location of interstrand
      crosslinks formed by cisplatin.

PMID- 18092836
TI  - Microcalorimetric investigation of DNA, poly(dA)poly(dT) and poly[d(A-C)]poly[d(G
      T)] melting in the presence of water soluble (meso tetra (4 N oxyethylpyridyl)
      porphyrin) and its Zn complex.
AB  - Thermodynamic parameters of melting process (DeltaHm, Tm, DeltaTm) of calf thymus
      DNA, poly(dA)poly(dT) and poly(d(A-C)).poly(d(G-T)) were determined in the
      presence of various concentrations of TOEPyP(4) and its Zn complex. The
      investigated porphyrins caused serious stabilization of calf thymus DNA and poly
      poly(dA)poly(dT), but not poly(d(A-C))poly(d(G-T)). It was shown that TOEpyp(4)
      revealed GC specificity, it increased Tm of satellite fraction by 24 degrees C,
      but ZnTOEpyp(4), on the contrary, predominantly bound with AT-rich sites and
      increased DNA main stage Tm by 18 degrees C, and Tm of poly(dA)poly(dT) increased
      by 40 degrees C, in comparison with the same polymers without porphyrin.
      ZnTOEpyp(4) binds with DNA and poly(dA)poly(dT) in two modes--strong and weak
      ones. In the range of r from 0.005 to 0.08 both modes were fulfilled, and in the
      range of r from 0.165 to 0.25 only one mode--strong binding--took place. The weak
      binding is characterized with shifting of Tm by some grades, and for the strong
      binding Tm shifts by approximately 30-40 degrees C. Invariability of DeltaHm of
      DNA and poly(dA)poly(dT), and sharp increase of Tm in the range of r from 0.08 to
      0.25 for thymus DNA and 0.01-0.2 for poly(dA)poly(dT) we interpret as entropic
      character of these complexes melting. It was suggested that this entropic
      character of melting is connected with forcing out of H2O molecules from AT sites
      by ZnTOEpyp(4) and with formation of outside stacking at the sites of binding.
      Four-fold decrease of calf thymus DNA melting range width DeltaTm caused by
      increase of added ZnTOEpyp(4) concentration is explained by rapprochement of AT
      and GC pairs thermal stability, and it is in agreement with a well-known
      dependence, according to which DeltaT approximately TGC-TAT for DNA obtained from
      higher organisms (L. V. Berestetskaya, M. D. Frank-Kamenetskii, and Yu. S.
      Lazurkin. Biopolymers 13, 193-205 (1974)). Poly (d(A-C))poly(d(G-T)) in the
      presence of ZnTOEpyp(4) gives only one mode of weak binding. The conclusion is
      that binding of ZnTOEpyp(4) with DNA depends on its nucleotide sequence.

PMID- 18092837
TI  - Chemoprotective action of resveratrol and genistein from apoptosis induced in
      human peripheral blood lymphocytes.
AB  - Extensive research is being carried out to analyse the importance of plant
      products such as resveratrol and genistein, which are known to exert a variety of
      pharmacological effects. This study aims at evaluating the protective role of
      these compounds against the apoptosis induced in normal cells by cytotoxic
      anticancer agents such as cisplatin and mytomycin C during therapy. Despite the
      broad antineoplastic action of cisplatin and mitomycin C, their genotoxicity in
      normal cell might lead to the induction of secondary malignancies. Therefore, the
      problem of identifying plant compounds, which might exert protective action in
      normal cells, gains lot of significance. We have analyzed the chemoprotective
      effect of plant compounds on peripheral blood human lymphocytes when exposed to
      cisplatin and mitomycin C by pre-treating and post-treating them with resveratrol
      and genistein at 100 microM concentration Biochemical alterations occurring in
      many cells during apoptosis include loss of plasma membrane phospholipid
      asymmetry, DNA fragmentation, and activation of caspase-3, et cetera, and have
      been assessed. Fluorescence microscopy, flow cytometric techniques have clearly
      demonstrated that resveratrol and genistein are efficient in protecting
      lymphocytes undergoing DNA damage when exposed to cisplatin and mitomycin C and
      exerted their activity by reducing the caspase 3 expression. An interesting
      observation is that, these compounds offered their protective effect by reducing
      their apoptotic potential on membrane and nucleic acids against cytotoxic agents,
      cisplatin, and mitomycin C. These results suggest that resveratrol and genistein
      might be useful for risk assessments in advance of clinical trials and could be
      considered as a strong candidate in pharmacogenomics or nutriprotective arena.

PMID- 18092838
TI  - A model for separation and melting of deoxyribonucleic acid in replication and
      transcription processes.
AB  - In order to explain the denaturation and melting in replication and transcription
      of deoxyribonucleic acid (DNA) at physiological temperature, we propose a
      dynamical model on the basis of structure and motion of DNA under the actions of
      energy released in hydrolysis of adenosine triphosphate (ATP) and enzymes. The
      model admits three degrees of freedom per base pair: two displacement variables
      associated with the vibrations of hydrogen atom in the hydrogen bonds and base
      (nucleotide), respectively, and an angular variable describing the rotation of
      base. The important role of hydrogen atom in the hydrogen bonds is stressed in
      this model. The Hamiltonian of the intact double helix system is given first,
      subsequently the equations of motion and solutions of a melting system are
      developed. The solutions represent the excited states formed by the displacements
      of hydrogen atoms and bases and the rotations of bases, arising from the energy
      absorbed by DNA, respectively. The results obtained show that the displacements
      of hydrogen atoms increase with time and along the helix. Once the displacements
      of hydrogen atoms and rotations of bases reach to certain limits, the hydrogen
      bonds are disrupted, and the two double helical strands of DNA are separated, a
      melting state in the replication or transcription process occurs. The properties
      of thermal motion of hydrogen atoms in this state at physiological temperature is
      further studied by using a transfer integral method and the thermodynamic
      properties such as free energy and entropy of the thermally excited state are
      obtained in the process. Values of characteristic parameters and critical
      temperature of melting in transcription process are derived. Finally the validity
      of the theory was demonstrated through comparison between experimental and
      theoretical data of specific heat and force of phase transition. This
      investigation is helpful to understand mechanism and essence of the replication
      or transcription process and promote quantitative description of these processes.

PMID- 18092839
TI  - Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform
      exanthemata: first 120 cases from the literature including a series of six new
      patients.
AB  - Tumor necrosis factor-alpha (TNFalpha) inhibition is effective in the treatment
      of moderate-to-severe psoriasis. We report on 120 patients from the literature
      including six new patients (three women and three men) who developed pustular
      lesions during treatment with TNFalpha inhibitors. We identified 72 women and 36
      men (several papers did not specify the gender of patients) with an age range of
      13-78 years (mean 42.3 years). The primary diagnoses were rheumatoid arthritis (n
      = 61), ankylosing spondylitis (n = 21), psoriasis (n = 10), Crohn disease (n =
      8), SAPHO (synovitis acne pustulosis hyperostosis osteitis) syndrome (n = 3),
      psoriatic arthritis (n = 2), and other diagnoses (n = 15). Psoriasis (except
      palmoplantar pustular type) was the most common adverse effect during anti
      TNFalpha treatment (n = 73), followed by palmoplantar pustular psoriasis (n = 37)
      and psoriasis of the nail (n = 6), sometimes combined in the same patient.
      Palmoplantar pustulosis and psoriasiform exanthema was the diagnosis in ten
      patients each. A positive personal history of psoriasis was recorded in 25
      patients. A positive family history was noted in eight patients. No data about
      personal (n = 7) or family history (n = 46) were available in a number of
      patients. Newly induced psoriasis was diagnosed in 74 patients whereas an
      exacerbation or aggravation of a pre-existing psoriasis was noted in another 25
      patients. All three TNFalpha inhibitors available on the market were involved:
      infliximab (63 patients), etanercept (37 patients), and adalimumab (26 patients).
      Several patients were treated with more than a single TFNalpha inhibitor. The
      timing of cutaneous adverse effects (psoriasis and psoriasiform rash) varied
      considerably among patients, ranging from after a single application to a delayed
      response of up to 63 months after initiation of treatment. The mean time to
      appearance of the cutaneous adverse effect for all TNFalpha inhibitors was 9.5
      months. Cessation of the responsible TNFalpha inhibitor was carried out in 47
      patients either alone or in association with adjuvant anti-psoriatic therapy
      (mostly topical). This resulted in complete remission in 21 patients, partial
      remission in 20 patients, and stable disease in another three patients; in the
      other three patients, the outcome was not reported. TNFalpha inhibition was
      continued in 47 patients but anti-psoriatic adjuvant therapy was introduced. The
      outcome in this group was complete remission in 22 patients, partial remission in
      25 patients, and stable disease in 2 patients. The response rate (complete
      remission plus partial remission) was 93.2% and 95.9%, respectively, in each
      group. In six patients, switching from one TNFalpha inhibitor to another one
      immediately after cutaneous adverse effects occurred resulted in an improvement
      in five patients. In nine patients, a second TNFalpha inhibitor was initiated
      after a break in TNFalpha inhibition. The response to a second or third drug in
      these patients was mixed. The underlying pathomechanisms of induction of
      psoriasis or psoriasiform exanthemata by TNFalpha inhibitors remain elusive but
      there is reason to assume that induction of such adverse events has more than one
      pathophysiology.

PMID- 18092840
TI  - Peroxisome proliferator-activated receptors (PPARs) and the human skin:
      importance of PPARs in skin physiology and dermatologic diseases.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      receptor superfamily that regulate lipid, glucose, and amino acid metabolism.
      More recently, PPARs and corresponding ligands have been shown in skin and other
      organs to regulate important cellular functions, including cell proliferation and
      differentiation, as well as inflammatory responses. These new functions identify
      PPARs and corresponding ligands as potential targets for the treatment of various
      skin diseases and other disorders. It has been shown that in inflammatory skin
      disorders, including hyperproliferative psoriatic epidermis and the skin of
      patients with atopic dermatitis, the expression of both PPARalpha and PPARgamma
      is decreased. This observation suggests the possibility that PPARalpha and
      PPARgamma activators, or compounds that positively regulate PPAR gene expression,
      may represent novel NSAIDs for the topical or systemic treatment of common
      inflammatory skin diseases such as atopic dermatitis, psoriasis, and allergic
      contact dermatitis. Moreover, recent findings indicate that PPAR-signaling
      pathways may act as a promising therapeutic target for the treatment of
      hyperproliferative skin diseases including skin malignancies. Studies in non
      diabetic patients suggest that oral thiazolidinediones, which are synthetic
      ligands of PPARgamma, not only exert an antidiabetic effect but also may be
      beneficial for moderate chronic plaque psoriasis by suppressing proliferation and
      inducing differentiation of keratinocytes; furthermore, they may even induce cell
      growth arrest, apoptosis, and terminal differentiation in various human malignant
      tumors. It has been reported that PPARalpha immunoreactivity is reduced in human
      keratinocytes of squamous cell carcinoma (SCC) and actinic keratosis (AK), while
      PPARdelta appears to be upregulated. Additionally, the microvessel density is
      significantly higher in AK and SCC that express high levels of PPARdelta.
      PPARdelta has been demonstrated to have an anti-apoptotic role and to maintain
      survival and differentiation of epithelial cells, whereas PPARalpha and PPARgamma
      activators induce differentiation and inhibit proliferation and regulate
      apoptosis. In melanoma, the growth inhibitory effect of PPARgamma activation is
      independent of apoptosis and seems to occur primarily through induction of cell
      cycle arrest in the G1 phase of the cell cycle or induction of re
      differentiation. PPARalpha activation causes inhibition of migration of melanoma
      cells and anchorage-independent growth, whereas primary tumor growth remains
      unaltered. In clinical trials of gemfibrozil, a PPARalpha ligand, significantly
      fewer patients treated with this lipid-lowering drug were diagnosed with melanoma
      as compared to those in the control group. In conclusion, an increasing body of
      evidence indicates that PPAR signaling pathways may represent interesting
      therapeutic targets for a broad variety of skin disorders, including inflammatory
      skin diseases such as psoriasis and atopic dermatitis, and skin malignancies.

PMID- 18092841
TI  - Fractional photothermolysis for the treatment of striae distensae in Asian skin.
AB  - BACKGROUND: Striae distensae (SD) are dermal scars characterized by linear
      atrophic depressions. Fractional photothermolysis (FP) is an effective modality
      for the treatment of cutaneous scars. OBJECTIVE: To evaluate the safety and
      efficacy of FP for the treatment of SD in Asian skin. METHODS: Six female
      volunteers aged between 20 and 35 years with chronic striae albae phase SD on
      both buttocks were enrolled. SD lesions on the right buttock were irradiated with
      a 1550-nm FP laser and patients were followed every 4 weeks for a total of 8
      weeks. Outcome assessments included serial photographs, erythema index and
      melanin index tracking, skin elasticity, histologic examination, and the
      patients' subjective satisfaction scores. RESULTS: FP treatment was associated
      with a substantial improvement in the appearance of SD at 8 weeks post-treatment.
      The erythema index and melanin index of the treated SD lesions tended to converge
      with those of the control skin at 4-week follow-up. Skin elasticity was found to
      be partially normalized after FP. In addition, there was a significant increase
      in epidermal thickness, collagen, and elastic fiber deposition after FP as
      demonstrated by histologic examination. Adverse effects of FP included mild and
      transient pain and hyperpigmentation. CONCLUSION: FP can reduce SD by stimulating
      new collagen and elastic fiber synthesis. In addition, repetitive treatments
      might constitute an effective approach to improving the treatment of SD.

PMID- 18092842
TI  - Generalized pruritus: a prospective study concerning etiology.
AB  - BACKGROUND: Generalized pruritus can often be the primary manifestation of
      systemic disease. OBJECTIVE: To determine how frequently generalized pruritus had
      a systemic etiology in an outpatient population seen in a dermatology department
      and whether any identifiable patient characteristics meant a systemic explanation
      of generalized pruritus was more likely. METHODS: A prospective controlled study
      of 55 patients with generalized pruritus and 41 healthy age- and sex-matched
      control subjects. Clinical data were collected from patients and laboratory
      parameters investigated in both patients and healthy control subjects to
      determine the frequency of systemic disease in each group. RESULTS: Of 55
      patients, 12 had a systemic cause of pruritus. Pruritus was the initial symptom
      of systemic disease in eight of these patients. The underlying diseases included
      hypothyroidism, chronic lymphocytic leukemia, hepatitis C, hepatitis B, diabetes
      mellitus, lung cancer, uremia, and iron deficiency anemia. Of these, iron
      deficiency anemia was the most common cause. Compared with the control group,
      mean serum hemoglobin, iron, and cyanocobalamin (vitamin B(12)) levels in
      patients with generalized pruritus were lower. No other patient characteristics
      were statistically associated with systemic causes of pruritus. CONCLUSION:
      Generalized pruritus was the initial symptom of a systemic disease in 8 of 55
      patients presenting to a dermatology outpatient clinic with this complaint. A
      number of underlying diseases were identified, of which the most common was iron
      deficiency anemia.

PMID- 18092843
TI  - Comparison of skin hydration evaluation sites and correlations among skin
      hydration, transepidermal water loss, SCORAD index, Nottingham Eczema Severity
      Score, and quality of life in patients with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is characterized by dryness of the skin,
      pruritus and involvement of the skin flexures. Skin hydration (SH) and integrity,
      as measured by transepidermal water loss (TEWL), are important parameters for
      objectively quantifying AD research. OBJECTIVES: To evaluate if sites in the
      forearm are equivalent to the antecubital fossa for standard SH and TEWL
      measurements; and to determine the correlations among these measurements and
      scores of disease severity and quality of life. METHODS: We evaluated SH and TEWL
      under standardized conditions at three common measurement sites in the forearm
      (antecubital flexure, 2 cm below the antecubital flexure, mid-forearm), and
      determined the SCORing Atopic Dermatitis (SCORAD) score, Nottingham Eczema
      Severity Score (NESS), and Children's Dermatology Life Quality Index (CDLQI).
      RESULTS: Significant correlations between clinical scores, SH, and TEWL were
      obtained at a site 2 cm below the antecubital fossa (r = -0.553, p < 0.001 for SH
      and SCORAD; r = 0.596, p < 0.001 for TEWL and SCORAD). SH and TEWL were also
      correlated with long-term severity of AD as measured by NESS (r = -0.494, p =
      0.001 for SH; r = 0.430, p = 0.004 for TEWL), while TEWL was significantly
      correlated with CDLQI (r = 0.323, p = 0.035). Overall, similar significant
      correlations were obtained at the mid-forearm, but less so at the antecubital
      fossa. CONCLUSION: In AD research, three sites on the forearm appear to be
      convenient for determination of SH and TEWL. This is the first report to
      demonstrate that significant correlations are obtained among acute and chronic
      scores of AD disease severity, quality of life, and the bioengineering
      parameters.

PMID- 18092844
TI  - Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) with absence of
      desmoglein 1 and 3 antibodies: case report and literature review.
AB  - Subcorneal pustular dermatosis (SPD) [Sneddon-Wilkinson disease] is a benign and
      uncommon disorder characterized by a chronic, relapsing vesiculopustular eruption
      of unknown etiology. We present a case of SPD in a young Black woman in whom
      ELISA was performed to test for desmoglein 1 and 3 antigens (the first reported
      case of evaluation for these antigens in a patient with SPD). The test revealed
      the absence of both antibodies. The patient was successfully treated with topical
      corticosteroids and narrow-band UVB phototherapy. In this report, we review both
      the pathophysiology of SPD, which has yet to be clarified, and its treatment.
      Data obtained from our case report add further support to the hypothesis that a
      non-antibody-mediated mechanism is operative in SPD. The treatment of choice for
      SPD is dapsone. However, the combination of corticosteroids and UVB phototherapy
      should be considered a valid therapeutic option in patients who are not
      appropriate candidates for dapsone therapy.

PMID- 18092845
TI  - Coexistence of Mayer-Rokitansky-Kuster-Hauser syndrome and neurofibromatosis type
      I.
AB  - Neurofibromatosis type 1 (NF-1) is the most frequently seen form of
      neurofibromatosis. The characteristic features of this disorder are cafe au lait
      macules, neurofibromas, axillary and inguinal freckling, Lisch nodules, bone
      lesions such as sphenoid dysplasia, and optic glioma. Mayer-Rokitansky-Kuster
      Hauser (MRKH) syndrome is a rarely seen disease characterized by complete vaginal
      agenesis and uterine aplasia/hypoplasia. We report a case of an 18-year-old
      female patient who presented with complaints of brown marks, freckling, and
      primary amenorrhea. NF-1 and MRKH syndrome were diagnosed by physical examination
      and radiologic imaging. To our knowledge, this is the first report of coexistence
      of these rare genetic diseases in the literature.

PMID- 18092846
TI  - Recurrent chondrosarcoma of the right skull base in a patient with Maffucci
      syndrome.
AB  - Maffucci syndrome is a rare, sporadic disease characterized by the development of
      multiple enchondromas and subcutaneous hemangiomas. Patients with Maffucci
      syndrome have a 23-37% risk of malignancy, with chondrosarcomas being the most
      common. Although the development of a chondrosarcoma in a patient with Maffucci
      syndrome may be expected, intracranial chondrosarcomas are rare. We present a
      patient with Maffucci syndrome who was diagnosed with an intracranial
      chondrosarcoma after presenting with hearing loss and vomiting. After three
      craniotomies and two recurrences of chondrosarcoma of the right skull base, the
      patient demonstrated a positive outcome to treatment with external radiation
      therapy.

PMID- 18092847
TI  - Unilateral thoracic erythema with induration.

PMID- 18092848
TI  - Arsenic bioavailability in the soil amended with leaves of arsenic
      hyperaccumulator, Chinese brake fern (Pteris vittata L).
AB  - An incubation experiment was carried out to better understand the fate of As
      during the decomposition of As-rich Chinese brake fern (Pteris vittata L.) leaves
      and to assess As bioavailability in soil. Dried fern leaves with an As
      concentration of 1,150 +/- 14 microg/g were amended with unpolluted soil at 1 and
      3%. After aging for one, three, and six months, germinated wheat was planted in
      the soil. After two months, wheat plants were harvested. Results showed that As
      concentration in shoots and roots significantly increased with increasing amounts
      of As-rich leaf additions in soil samples and decreased over the incubation time
      (p < 0.001). For treatments with 3% fern leaf incubation, the average of As
      concentration in shoots was 1.59 microg/g dry weight after one month of
      incubation, nearly 20-fold higher than that of the nonamended treatment; after
      six months of incubation, As concentration in shoots was 0.48 microg/g, almost 10
      fold higher than the corresponding nonamended treatment. Based on a sequential
      extraction method, As showed a shift from weakly adsorbed fractions to more
      strongly adsorbed fractions during the incubation, hence resulting in less As
      bioavailability. Arsenic concentrations in shoots and roots could be well
      described with linear functions of As concentrations distributed in different
      fractions. In conclusion, aging effect should be considered during risk
      assessment of As in soil-plant systems where As is recycled by the plant.

PMID- 18092849
TI  - Effect of sediment particle size on polycyclic aromatic hydrocarbon
      biodegradation: importance of the sediment-water interface.
AB  - Mechanisms for the effects of sediment on the biodegradation of organic compounds
      in the aquatic environment are not clear. In this research, effects of sediment
      characteristics on biodegradation kinetics of chrysene and benzo[a]pyrene were
      studied by inoculating polycyclic aromatic hydrocarbon (PAH)-degrading bacteria.
      Because water and PAHs can pass a polytetrafluoroethylene membrane yet bacteria
      and sediment cannot, a membrane experiment was performed to compare the
      biodegradation rates of PAHs in water and at the sediment-water interface,
      providing direct evidence that the PAH biodegradation rate is enhanced by the
      presence of sediment. Biodegradation of PAHs in water-sediment systems was fitted
      to zero-order kinetics; the order of biodegradation rate in water-sediment
      systems with different sediment was fine silt > clay > coarse silt.
      Biodegradation of PAHs in water-sediment systems occurred mainly at the sediment
      water interface. According to membrane experiment results, when the
      biodegradation kinetics was fit to a zero-order equation, the maximum specific
      growth rates of bacteria (1/d) at the sediment-water interface were approximately
      three- to fourfold those in the water phase. Furthermore, the associated
      mechanisms regarding the effect of sediment characteristics were analyzed by
      investigating the process of bacterial growth and the distribution of bacteria
      and PAHs between water and sediment phases.

PMID- 18092850
TI  - Multiresidue determination of fluoroquinolone, sulfonamide, trimethoprim, and
      chloramphenicol antibiotics in urban waters in China.
AB  - A feasible method has been optimized to simultaneously determine multiclass
      antibiotic residues, including sulfonamides, fluoroquinolones, trimethoprim, and
      chloramphenicol in urban riverine water and wastewater by off-line solid phase
      extraction and high-performance liquid chromatography coupled with a diode-array
      ultraviolet detector and a fluorescence detector. Internal standard and standard
      addition methods were used in combination to identify and quantify these
      antibiotics to compensate for the matrix interference. The method quantification
      limits (MQLs) were determined to be 0.035 to 0.100 microg/L and 0.100 to 0.300
      microg/L for the riverine water and wastewater, respectively. Recoveries of the
      investigated antibiotics ranged from 63 to 126%. Sulfamethoxazole was the most
      frequently detected antibiotic residue in Guangzhou section of the Major Pearl
      River, South China, with a maximum level of 0.510 microg/L. Fluoroquinolone
      antibiotics were relatively less detected with a maximum level of 0.459 microg/L.
      The maximum concentration of sulfamethoxazole reached 5.597 microg/L in the raw
      wastewater from a large-scale sewage treatment plant in Guangzhou city. Around
      30% of sulfamethoxazole might survive the primary clarification and biotreatment
      processes in the sewage treatment plant. None of the investigated antibiotics
      have been found above MQLs in the final effluent after chlorine disinfection.

PMID- 18092851
TI  - Interaction between carbamazepine and humic substances: a fluorescence
      spectroscopy study.
AB  - Carbamazepine is a popular drug that has been detected in natural environments,
      but little is known about its biogeochemical cycling, influencing factors, and
      eco-environmental effects in aquatic ecosystems. Interaction between
      carbamazepine and humic substances, including fulvic and humic acids, was studied
      using three-dimensional excitation-emission matrix fluorescence spectroscopy and
      synchronous-scan fluorescence spectroscopy. The intrinsic fluorescence of humic
      substances was quenched on the addition of carbamazepine, and static quenching
      was the primary mechanism. The binding parameters on their interaction, including
      the conditional binding constants (log K) and binding capacities (C(L)), were
      estimated by the Ryan-Weber nonlinear theory equation. Log K ranged from 3.41 to
      5.04 L/mol at 25 degrees C and pH 7.0. The influence of pH on the complexation
      and the competition between carbamazepine and Cu(II) for fluorescence-binding
      sites also were discussed. The present results would be helpful in understanding
      the fate and biogeochemical cycling of other pharmaceuticals and personal care
      products in aquatic ecosystems.

PMID- 18092852
TI  - Response of the freshwater Alga chlorella vulgaris to trichloroisocyanuric acid
      and ciprofloxacin.
AB  - The effects of trichloroisocyanuric acid (TCCA) and ciprofloxacin (CPFX) on the
      freshwater alga Chlorella vulgaris were assessed by toxicity bioassays and by the
      values of biomarkers in phase I and phase II. The biomarkers included growth
      rate, concentration of chlorophyll a, activities of 7-ethoxyresorufin-O
      dealkylases (EROD), glutathione S-transferase (GST), catalase (CAT), and total
      glutathione (GSH). Ciprofloxacin was a weaker growth inhibitor than TCCA but, at
      a concentration of greater than 12.5 mg/L, decreased the growth of C. vulgaris.
      Concentration of chlorophyll a showed a similar trend. The 96-h median effective
      concentration (EC50; i.e., 50% reduction in growth relative to the control) of
      CPFX was 20.6 mg/L. Trichloroisocyanuric acid was a strong growth inhibitor and,
      at concentrations of greater than 0.80 mg/L, caused 100% inhibition on 24-h
      exposure. The 96-h EC50 of TCCA was 0.313 mg/L. Ciprofloxacin and TCCA affected
      the phase I and phase II enzyme activities differently. On exposure to CPFX, both
      EROD and GSH decreased at low CPFX concentrations (<5.0 mg/L) and increased at
      high CPFX concentrations (>12.5 mg/L), and CAT and GST exhibited induction at low
      concentrations and inhibition at high concentrations. In TCCA exposure, GST
      activity was significantly stimulated, and GSH concentration was increased.
      Catalase activity increased only at TCCA concentrations of greater than 0.12
      mg/L, and no change in EROD activity was observed.

PMID- 18092853
TI  - Characterization and loading estimation of polycyclic aromatic hydrocarbons in
      road runoff from urban regions of Beijing, China.
AB  - This paper reports an initial study regarding our quantitative understanding of
      the characteristics of polycyclic aromatic hydrocarbon (PAH) contamination and
      loading estimation from road runoff in Beijing (China). The concentrations of 16
      PAHs were measured in road runoff and rainwater in a composite commercial and
      residential catchment of Beijing in 2006. In road runoff samples, geometric mean
      concentrations of Sigma16 PAHs (the sum of 16 PAH concentrations) in the
      dissolved and particle phases were 548.2 and 3,872.2 ng/L, respectively, and in
      rainwater samples, the concentrations in the dissolved and particle phases were
      172.9 and 274.6 ng/L, respectively. An analysis on spatial variation among the
      sampling sites showed that PAH concentrations at the branch road (with low
      traffic volume) were higher than those at the trunk road (with high traffic
      volume) and that PAH contamination at the bicycle lane was comparable to that at
      the vehicle lane. Dimensionless cumulative analyses indicated that first flush
      effect did not occur in all cases, but rather depended on storm event
      characteristics. According to the annual unit loading rate and the planned road
      area, the relative magnitude of PAH loading in road runoff was in the following
      order: Vehicle lane of trunk road > branch road > bicycle lane of trunk road.

PMID- 18092854
TI  - Fate of estrogens and xenoestrogens in four sewage treatment plants with
      different technologies.
AB  - The fate and removal of the estrogens 17beta-estradiol (E(2)), estrone (E(1)),
      and 17alpha-ethynylestradiol (EE(2)) and of the xenoestrogens bisphenol A (BPA),
      4-tert-octylphenol (4-t-OP), 4-nonylphenol (4-NP), and nonylphenol mono- and
      diethoxylate (NPEO1 and NPEO2, respectively) were investigated in four South
      Australian sewage treatment plants (STPs; plants A-D) with different treatment
      technologies. The concentrations in the effluent from the two-year survey were
      similar to those reported in other studies. In the effluent, 4-NP, NPEO1, and
      NPEO2 had total concentrations up to 8 microg/L, which were much higher than
      those of BPA and 4-t-OP. Estrone had the highest concentrations among the three
      estrogens, ranging between 13.3 and 39.3 ng/L, whereas the concentrations for
      E(2) and EE(2) varied between 1.0 and 4.2 ng/L and between 0.1 and 1.3 ng/L,
      respectively. The removal rates for the estrogens and xenoestrogens were variable
      but consistent with the plant performance parameters (biochemical oxygen demand,
      suspended solids, and ammonia). Considering all the estrogenic compounds analyzed
      in the present study, plant D, with a series of anaerobic and aerobic lagoons,
      was the least efficient of the four STPs in the removal of these compounds. The
      removal rates for 4-NP, NPEO1, and NPEO2 within the plants were 92% for plant A,
      with conventional activated sludge treatment; 80% for plant B, with two oxidation
      ditches; 70% for plant C, with three bioreactors; and 64% for plant D, with 10
      lagoons in series. Comparatively, the removal of estrogens was lower, with rates
      ranging between 47 and 68% for E(2) at the four plants. Both E(1) and EE(2) were
      more persistent during treatment, especially in plants C and D.

PMID- 18092855
TI  - Influences of metal-ligand complexes on the cadmium and zinc biokinetics in the
      marine bacterium, Bacillus firmus.
AB  - Uptake kinetics of cadmium and zinc in gram-positive bacteria, Bacillus firmus,
      isolated from Hong Kong sediments were examined in the present study. The metal
      uptake by the bacteria was measured at different ambient free metal ion
      concentrations (10(-12)-10(-6) M Cd(2+) and 10(-10)-10(-6) M Zn(2+)) by adding
      different concentrations of total dissolved Cd and Zn and hydrophilic organic
      ligands (ethylenedinitrilotetraacetic acid, nitrilotriacetic acid, and citrate).
      Our data suggest that Cd and Zn uptake by B. firmus is best predicted by Cd(2+)
      and Zn(2+) activities. Free metal ions were complexed with the active sites on
      the bacterial surface, and an equilibrium between the free metal ion and surface
      metal complex was reached quickly. After binding, the metal ions were then
      biologically transported into the bacteria. In addition, with the presence of
      lipophilic organic ligands (diethyldithiocarbamate and oxine), the lipophilic
      metal complex was internalized rapidly into B. firmus by passive diffusion
      through the bacterial plasma membrane. The uptake of the lipophilic metal complex
      could not be predicted by the free ion activity model because the mass transport
      through plasma membrane was the most important metal uptake pathway. Furthermore,
      the efflux of Cd and Zn by B. firmus was determined in the present study. The
      calculated efflux rate constants of Cd and Zn were (5.55 +/- 1.96) x 10(-4)/min
      and (3.75 +/- 1.04) x 10(-4)/min, respectively. The present study helps us to
      understand the process of bioaccumulation of metals in marine bacteria, which
      remains a poorly studied area.

PMID- 18092856
TI  - Methylmercury extraction from artificial sediments by the gut juice of the
      sipunculan, Sipunculus nudus.
AB  - Artificially prepared sediments were used to investigate their binding with
      methylmercury (MeHg). The bioavailability of sediment-bound MeHg then was
      quantified by measuring the extraction by gut juice of the sipunculan Sipunculus
      nudus, as well as by different free amino acids and bovine serum albumin (BSA).
      Methylmercury distribution in different molecular weight- size fractions of gut
      juice also was determined using an ultrafiltration methodology. Organic and clay
      content were the two most important sediment components in MeHg partitioning, but
      most of the sediment-bound MeHg was complexed by organic matter (fulvic acid >
      humic acid) in sediments. Treatment with humic or fulvic acid generally increased
      the amount of bioavailable MeHg. Cysteine was more important than other amino
      acids in MeHg extraction. Proteins (especially >100 kDa fraction) in gut juice
      rather than free amino acids were the main agents in gut juice that extracted
      MeHg from sediments. Most extracted MeHg from artificial sediments was associated
      with the >100 kDa fraction (probably proteins) of gut juice but not with organic
      matter from sediments (humic acid and fulvic acid). Our results suggested that
      competition among different agents in gut juice (especially the large molecular
      weight proteins) and the organic content of the sediments controlled the
      bioavailability of sediment-bound MeHg.

PMID- 18092857
TI  - A two-hybrid yeast assay to quantify the effects of xenobiotics on thyroid
      hormone-mediated gene expression.
AB  - Over the last few years, increasing evidence has become available that some
      chemicals may have thyroid hormone- disrupting potencies. The effects exerted via
      thyroid hormone receptors (TR) have not been studied thoroughly. The present
      study investigates chemical thyroid hormone disruption at the level of TR
      functioning. To this end the (ant)agonistic action of a series of xenobiotics was
      tested in the newly developed yeast two-hybrid assay. This assay makes use of
      recombined TRbeta gene and reporter gene yeast, which specifically expresses beta
      galactosidase when incubated with exogenous 3,3',5-triiodo-l-thyronine (T(3)).
      Agonistic and antagonistic actions were studied in the absence and presence of 5
      x 10(-6) mol/L T(3), which induced maximal beta-galactosidase activity. The
      compounds tested included the specific TR-antagonist amiodarone, as well as a
      series of phenols, phthalate, organochlorine pesticides (OCPs), polyhalogenated
      aromatic hydrocarbons (PHAHs) with structural similarity to T(3), and 3,3',5,5'
      tetraiodo-l-thyronine (T(4)). The results obtained reveal that only 2-t
      butylphenol and 2-isopropylphenol are specific agonists. Interestingly, some
      compounds showed potentiated antagonistic effects when tested in combination with
      T(3), which suggests that TR-mediated transcription may be disrupted in vivo. The
      20% relative inhibitory concentration (RIC20) values of phenols, ester and OCPs
      were more than 10(-7) mol/L, but the values for PHAHs with metabolization were
      lower than 5 x 10(-7) g/L. These results suggest that PHAHs pose a serious threat
      to the human thyroid system. Altogether the results of the present study show
      that the newly developed, yeast two-hybrid assay can be used as a valuable tool
      for identification and quantification of compounds active in disturbing thyroid
      hormone homeostasis at the level of TR. The results are further evidence of
      thyroid-related effects of environmentally relevant PHAHs.

PMID- 18092858
TI  - Organochlorine pesticides in the surface water and sediments of the Pearl River
      Estuary, South China.
AB  - Samples of surface water, suspended particulate matter (SPM), and surface
      sediment, collected from the Pear River Estuary, Guangdong Province, China in
      July of 2002 and April of 2003, were analyzed for hexachlorocyclohexanes (HCHs)
      and dichlorodiphenyltrichloroethanes (DDTs) using gas chromatography with
      electron capture detection. The levels of total HCHs in water varied from 213 to
      3,116 pg/L, although in sediments they ranged from 181 to 1,388 pg/g dry weight.
      The levels of DDTs were in the range of 228 to 3,284 pg/L in water and 57 to
      2,244 pg/g dry weight in sediments, respectively. The observed spatial and
      temporal variability of concentrations of the target compounds in water body
      could be attributed to the differences of SPM contents in water body and organic
      carbon contents in SPM between the two sampling periods. Seven of the 10 water
      samples collected in July of 2002 had the ratio of
      dichlorodiphenyltrichloroethane/(dichlorobischlorophenylethane +
      dichlorodiphenyldichloroethylene) (DDT/[DDD + DDE]) higher than one, indicating
      that there were likely fresh inputs of DDT to the Pearl River Estuary. The
      significant positive correlations between the organochlorine pesticide
      concentrations and organic carbon contents in SPM and sediments indicated that
      organic matter played an important role in controlling the distributions of these
      pollutants in the marine environment. Varied correlations between the partition
      coefficients of pollutants and total organic carbon, salinity, and total SPM
      contents have been observed, which indicated the influences of these factors on
      controlling the transport and fate of pollutants in the marine environment.

PMID- 18092859
TI  - Toxicological safety assessment of genetically modified Bacillus thuringiensis
      with additional N-acyl homoserine lactonase gene.
AB  - The aim of the present study is to evaluate the toxicology safety to mammals of a
      genetically modified (GM) Bacillus thuringiensis with an additional N-acyl
      homoserine lactones gene (aiiA), which possesses insecticidal activity together
      with restraint of bacterial pathogenicity and is intended for use as a
      multifunctional biopesticide. Safety assessments included an acute oral toxicity
      test and 28-d animal feeding study in Wistar rats, primary eye and dermal
      irritation in Zealand White rabbits, and delayed contact hypersensitivity in
      guinea pigs. Tests were conducted using spray-dried powder preparation. This GM
      product showed toxicity neither in oral acute toxicity test nor in 28-d animal
      feeding test at a dose of 5,000 mg/kg body weight. During the animal feeding
      test, there were no significant differences in growth, food and water
      consumption, hematology, blood biochemical indices, organ weights, and
      histopathology finding between rats in controls and tested groups. Tested animals
      in primary eye and dermal irritation and delayed contact hypersensitivity test
      were also devoid of any toxicity compared to controls. All the above results
      demonstrated that the GM based multifunctional B. thuringiensis has low toxicity
      and low eye and dermal irritation and would not cause hypersensitivity to
      laboratory mammals and therefore could be regarded as safe for use as a
      pesticide.

PMID- 18092860
TI  - Influences of 4-nonylphenol on doublesex- and mab-3-related transcription factor
      1 gene expression and vitellogenin mRNA induction of adult rare minnow
      (Gobiocypris rarus).
AB  - The mab-3 of Caenorhabditis elegans and doublesex of Drosophila are two sex
      determining genes that are found to have only a common DNA binding motif called a
      doublesex and mab-3 (DM) domain among phyla. The DM domain regulates some aspects
      of sexual development such as yolk protein synthesis. In the present study, by
      using DM degenerate primers' 13 sequences of doublesex and mab-3-related
      transcription factor (dmrt), genes were cloned from genomic DNA of rare minnow
      (Gobiocypris rarus) and expression of dmrt1 was detected only in testis of adult
      males. In addition, partial sequences of vitellogenin (vtg) and beta-actin genes
      as comparative expression of genes were cloned from the female liver by
      degenerate primers based on conserved regions. The vtg mRNA in male liver was
      induced significantly in concentrations higher than 2 microg/L treatments,
      although adult rare minnow were exposed to nominal concentrations of 2, 10, 50,
      250, and 1,250 microg/L 4-nonylphenol (4-NP) for 21 d. The dmrt1 mRNA level was
      significantly downregulated in a dose-dependent manner in all exposure groups of
      males. Moreover, other toxic endpoints, including growth, gonadosomatic index,
      hepatosomatic index, and histopathology, were determined. However, significant
      effects were observed only at higher exposure concentrations. Therefore, sex
      specific genes such as dmrt1 can be used as a more sensitive biomarker for 4-NP
      and for discovering molecular mechanisms underlying toxic response.

PMID- 18092861
TI  - Seasonal variations of estrogenic compounds and their estrogenicities in influent
      and effluent from a municipal sewage treatment plant in China.
AB  - The seasonal variations of estrogenic compounds and the estrogenicities of
      influent and effluent were investigated by chemical analysis and in vitro assay
      in a municipal sewage treatment plant in Wuhan (China). The levels of eight
      estrogenic compounds, including 17beta-estradiol (E(2)), estrone (E(1)), estriol
      (E(3)), diethylstilbestrol (DES), 17alpha-ethinylestradiol, nonylphenol (NP), 4
      tert-octylphenol (OP), and bisphenol A (BPA), were measured by gas chromatography
      mass spectrometry. Total estrogenic activity of sewage was quantitatively
      assessed using primary cultured hepatocytes of male Megalobrama amblycephala Yih
      using vitellogenin as a biomarker. The E(2) equivalents (EEQs) obtained from the
      chemical analysis were consistent with those measured by bioassay. The natural
      (E(1), E(2), and E(3)) and synthetic (DES) estrogens, as well as NP, were the
      main contributors of the total EEQs of influent and effluent in the present
      study. The levels of natural estrogens E(1) and E(3) in the influent and effluent
      were higher in winter than in summer, whereas the situation for NP and OP was the
      reverse. The levels of E(2), DES, and BPA varied little among different seasons.
      17alpha-Ethinylestradiol was not detected in the influent and effluent. The
      estrogenicities of the influent and of the primary and secondary effluents were
      all higher in summer than in winter. Estrogenic activities in winter mainly
      originated from natural (E(1), E(2), and E(3)) and synthetic (DES) estrogens,
      whereas the increase of EEQs in summer was contributed by NP. The results from
      chemical analysis and bioassay demonstrate that estrogenic compounds cannot be
      entirely removed by the existing sewage treatment process, which should be
      further improved to protect aquatic ecosystems and human health.

PMID- 18092862
TI  - Oxidative damage in unfertilized eggs of Chinese rare minnow (Gobiocypris rarus)
      exposed to nonylphenol.
AB  - In the present study, female Chinese rare minnows (Gobiocypris rarus) were used
      as in vivo models and exposed to nonylphenol (NP) at concentrations of 1 to 200
      microg/L for 21 d under semistatic conditions. Molecular biomarkers of oxidative
      stress were measured in unfertilized eggs and included reactive oxygen species
      (ROS), lipid peroxidation products (thiobarbituric acid- reactive substances
      [TBARS] and protein carbonyl), superoxide dismutase activity, and glutathione.
      Cathepsin D activity as an indicator of egg viability also was assayed.
      Nonylphenol induced ROS formation in unfertilized eggs in all exposed groups
      compared to the controls. The levels of protein carbonyl and TBARS in
      unfertilized eggs were significantly increased (p < 0.05) at 10 to 200 and 100 to
      200 microg/L, respectively. Good positive correlations were shown between ROS
      induction and levels of TBARS and protein carbonyl in eggs (R = 0.918, p < 0.05
      and R = 0.784, p < 0.05, respectively). Superoxide dismutase activity in eggs was
      significantly inhibited (p < 0.05) in the 50 to 200 microg/L exposure groups.
      Glutathione levels in eggs were significantly depleted (p < 0.05) at 100 to 200
      microg/L concentrations. In addition, ROS induction resulted in oxidative damage
      to lipid and protein in chorions. Significant reductions (p < 0.05) of the
      protein and lipid contents in chorions were both found in the 50 to 200 microg/L
      exposure groups. A previous study found that NP exposure could lead to chorion
      thinning in zebra fish. Thus, the reductions in protein and lipid contents in
      chorion could be the reason for chorion thinning by NP exposure. Meanwhile,
      cathepsin D activity was significantly inhibited (p < 0.05) in all exposure
      groups. The results demonstrated that NP-induced oxidative stress could damage
      the chorion of unfertilized eggs and lead to a decline in gamete quality in
      female Chinese rare minnow.

PMID- 18092863
TI  - Deriving site-specific sediment quality guidelines for Hong Kong marine
      environments using field-based species sensitivity distributions.
AB  - Field data of benthic communities and contaminant loadings in marine sediments
      measured in parallel can be used to derive sediment quality guidelines (SQGs)
      using a field-based species sensitivity distribution (f-SSD) approach. Recently,
      SQGs have been successfully derived from f-SSDs for the Norwegian continental
      shelf with an extensive survey (>1 million km(2)) and a large data set (1,902
      sampling stations with 1,944 species). The present study examined the
      practicality of this approach in deriving SQGs for a much smaller geographical
      area, namely, the marine environment of Hong Kong (sea area: 1,651 km(2)), making
      use of databases of the government of Hong Kong special administrative region. As
      the construction of f-SSDs requires the use of a collection of responses from
      individual species to a chemical gradient in sediment, data screening criteria on
      the minimum abundance of the species were evaluated and optimized to ensure
      sufficient statistical power for estimating these responses. Sediment quality
      guidelines were derived for nine trace metals, total polycyclic aromatic
      hydrocarbons, and total polychlorinated biphenyls and compared with current SQGs
      in developed countries. The community-adjusted hazardous concentrations of 5% and
      10% of the f-SSDs were adopted to represent the threshold effects level (TEL) and
      predicted effects level (PEL), respectively. The TELs derived from this f-SSD
      approach compares favorably with current SQGs, while the derived PELs were
      generally lower than the current SQGs, indicating that they are more protective.
      The f-SSDs can be directly utilized for probabilistic risk assessment, while the
      field-based SQGs can be used as site-specific guidelines or integrated into
      current SQGs. Our results suggest that the f-SSD approach can also be applicable
      to small areas such as Hong Kong.

PMID- 18092864
TI  - Determination and fate of oxytetracycline and related compounds in
      oxytetracycline production wastewater and the receiving river.
AB  - This study investigated the occurrence and fate of oxytetracycline (OTC) and its
      related substances, 4-epi-oxytetracycline (EOTC), alpha-apo-oxytetracycline
      (alpha-apo-OTC), and beta-apo-oxytetracycline (beta-apo-OTC), in a wastewater
      treatment plant (WWTP) treating OTC production wastewater and a river receiving
      the effluent from the WWTP using liquid chromatography electrospray ionization
      mass spectrometry (LC-ESI-MS). The percent removal of OTC in the WWTP was 38.0 +/
      10.5%, and the concentration of OTC was still up to 19.5 +/- 2.9 mg/L in the
      treated outflow. The concentration slightly decreased along the river, from 641
      +/- 118 microg/L at site R2 (discharging point) to 377 +/- 142 microg/L at site
      R4 ( approximately 20 km from site R2), which was still higher than the minimal
      inhibition concentration of OTC reported ( approximately 250 microg/L). On the
      other hand, the total amount of its related substances in the treated effluent
      was less than 5% of OTC. Concentrations of alpha-apo-OTC and beta-apo-OTC
      increased along the river, from 5.76 +/- 0.63 and 2.08 +/- 0.30 microg/L at site
      R2 to 11.9 +/- 4.9 and 12.0 +/- 4.6 microg/L at R4, respectively, although EOTC
      decreased from 31.5 +/- 3.8 to 12.9 +/- 1.1 microg/L, respectively. The mean
      concentration of beta-apo-OTC in river sediments was 20.8 +/- 7.8 mg/kg, and its
      ratio to OTC was approximately 0.11, nearly twice the ratio of alpha-apo-OTC and
      EOTC to OTC (0.058 +/- 0.014 and 0.061 +/- 0.015, respectively).

PMID- 18092865
TI  - Resistant desorption of hydrophobic organic contaminants in typical chinese
      soils: implications for long-term fate and soil quality standards.
AB  - Soil contamination is an enormous problem in China and severely threatens
      environmental quality and food safety. Establishing realistic soil quality
      standards is important to the management and remediation of contaminated sites
      and must be based on thorough understanding of contaminant desorption from soil.
      In the present study, we evaluated sorption and desorption behaviors of
      naphthalene, phenanthrene, atrazine, and lindane (four common soil contaminants
      in China) in two of the most common Chinese soils. The desorption of these
      compounds exhibited clear biphasic pattern-a fraction of contaminants in soil was
      much less available to desorption and persisted much longer than what was
      predicted with the conventional desorption models. The unique thermodynamic
      characteristics associated with the resistant-desorption fraction likely have
      important implications for the mechanism(s) controlling resistant desorption.
      Experimental observations in the present study are consistent with our previous
      work with chlorinated compounds and different adsorbents and could be well
      modeled with a biphasic desorption isotherm. We therefore suggest that more
      accurate biphasic desorption models should be used to replace the conventional
      linear sorption/desorption model that is still widely adopted worldwide in
      contaminant fate prediction and soil quality standard calculations.

PMID- 18092866
TI  - Heavy metals in wetland plants and soil of Lake Taihu, China.
AB  - Properties of vertical distribution of soil near water bodies are vary
      considerably from those of land and may greatly affect the transportation of
      heavy metals in wetlands. Vertical distributions of heavy metals (Cr, Cd, Cu, Pb,
      and Zn) in the soil of aquatic-terrestrial ecotone (ATE) of Lake Taihu, China,
      and in wetland plant tissues were studied. Generally, concentrations of heavy
      metals decreased with increasing depth in the top 40-cm cores and then increased
      slightly with increasing depth. This investigation indicated that concentrations
      of Cd, Cr, Pb, and Zn exceeded the geochemical background values in the Taihu
      Lake area. Concentrations of Cd at all depth soil columns exceeded the
      Environment Quality Standard for Soils of China. Correlation analysis showed that
      concentrations of Zn, Cr, Cd, and Pb correlated significantly with one another,
      suggesting that they had the same origin. The concentration of Cu was negatively
      correlated with root biomass, which may explain the lower concentration of copper
      in the soil cores. The dominant plants of the wetland were Phragmites australis
      and Ludwigia prostrata, and heavy metal accumulated primarily in the root tissue.
      The general order was root > rhizome > stem > leaf, whereas in L. prostrata, leaf
      was the main tissue for Cr accumulation. Both P. australis and L. prostrata had
      the highest concentration factor (CF) to Cu, and CF was 20.3 and 15.8,
      respectively. Aquatic-terrestrial ecotone plants are more effective in
      controlling Cu pollution than other heavy metals. This will be very significant
      for ATE reestablishment near Cu-polluted sites.

PMID- 18092867
TI  - Genotoxicity of total and fractionated extractable organic matter in fine air
      particulate matter from urban Guangzhou: comparison between haze and nonhaze
      episodes.
AB  - To investigate the genotoxic potencies of extractable organic matter (EOM) in
      aerosols, fine air particulate matter (PM(2.5)) was collected simultaneously at a
      roadside (1.2 m above ground) and at a rooftop location (50 m above ground) in
      urban Guangzhou (China) during a nonhaze period in September 2006 and a haze
      period in October 2006. Particle-bound organics were extracted and separated into
      aliphatic, aromatic, and polar fractions. The genotoxicity of total and
      fractionated extracts were tested by single-cell electrophoresis (comet assay)
      with human blood lymphocytes. The PM(2.5) concentrations usually exceeded the
      U.S. National Ambient Air-Quality Standard level (65 microg/m(3)) at both the
      roadside and the rooftop. During nonhaze days, the roadside samples showed
      substantially higher PM(2.5) levels (108-130 microg/m(3)) and significantly
      higher genotoxic effects of total and fractionated EOM (p < 0.05 for >10 m(3) air
      equivalent/ml) than the rooftop samples. During haze days, however, PM(2.5)
      levels and genotoxic potencies of rooftop samples were drastically elevated and
      comparable to those of roadside samples, implying that during haze episodes, most
      people in the urban area are exposed to PM(2.5) pollution as serious as in the
      heavily polluted roadside microenvironment. All total EOM samples showed
      significant (p < 0.05) dose-response effects, and their effects as olive tail
      moment were less than the sums of the three fractions. Aromatic fractions of EOM
      exhibited the greatest genotoxic potencies, but polar fractions also contributed
      substantially to DNA-damaging effects. Polycyclic aromatic hydrocarbons and
      nitrated derivatives likely are the most important species responsible for the
      genotoxicity of EOM in PM(2.5).

PMID- 18092868
TI  - Evaluation of estrogenicity of sewage effluent and reclaimed water using
      vitellogenin as a biomarker.
AB  - To evaluate the quality of reclaimed water, the estrogenicity of effluent from a
      sewage treatment plant and of reclaimed water treated with coagulation
      sedimentation-filtration using the effluent as raw water was assessed using
      vitellogenin (VTG) as a biomarker. After a three-week exposure, significant (p <
      0.05) induction of VTG occurred in female crucian carp (Carassius carassius)
      exposed continuously to the secondary effluent and reclaimed water with different
      dilutions (12.5, 25, 50, and 100% for secondary effluent; 50 and 100% for
      reclaimed water); no induction of VTG was detected when exposed to 12.5 and 25%
      reclaimed water. For male fish, however, only 100% secondary effluent induced the
      production of VTG (mean +/- standard deviation, 38.6 +/- 9.8 microg/ml). When the
      exposure time was prolonged to three months, VTG was induced significantly in
      both females and males at all gradient concentrations of secondary effluent and
      at 50 and 100% reclaimed water. The results indicated that no obvious VTG was
      detected in fish exposed to reclaimed water diluted more than fourfold. Ozonation
      of the secondary effluent under an ozone consumption dose of 8.5 mg/L resulted in
      a VTG level equal to that of 12.5% secondary effluent or 50% reclaimed water.
      Furthermore, VTG induction reflects the cumulative effects of estrogenic activity
      in the secondary effluent and reclaimed water compared with the in vitro assays,
      in which estrogenic activities in effluent changed markedly during the
      experiment.

PMID- 18092869
TI  - Tissue-dependent distribution and bioaccumulation of polychlorinated dibenzo-p
      dioxins and dibenzofurans in vegetation samples collected from Dongting Lake,
      China.
AB  - The concentration of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) were determined in soils and different species of vegetation collected
      from the Dongting Lake region, China. Use of sodium pentachlorophenate (Na-PCP)
      was the main contamination source of PCDD/Fs for soil/sediment and vegetation in
      the Dongting Lake region. Reed (Phragmitas communis Trin), Polygonum orientale
      L., and Artemisia selengensis Turcz ex Bess were selected as model plants to
      explore the pathway of PCDD/Fs transfer from contaminated soil to vegetation. In
      the vegetation tissue samples, the total international toxic equivalency values
      ranged from 0.14 to 1.64 pg international toxic equivalency/g dry weight with a
      mean value of 0.67 pg international toxic equivalency/g dry weight.
      Polychlorinated dibenzo-p-dioxins and dibenzofurans congener distribution and
      bioaccumulation varied among vegetation species. Polychlorinated dibenzo-p
      dioxins and dibenzofuran levels in the leaves were found to be higher than those
      in the root and stem, which were affected considerably by volatilization from
      contaminated soil. Volatilization from polluted soil and subsequent sorption to
      leaves may be a significant pathway for contamination of vegetation in Dongting
      Lake region.

PMID- 18092870
TI  - Distribution of polycyclic musks in surface sediments from the Pearl River Delta
      and Macao Coastal Region, South china.
AB  - Polycyclic musks were measured in surface sediments collected from the Pearl
      River Delta and Macao coastal region, South China, to investigate contamination
      from domestic sewage. Three polycyclic musk compounds-4-acetyl-1,1-dimethyl-6
      tert-butylindan, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2
      benzopyran (HHCB), and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4
      tetrahydronaphthalene (AHTN)-were detected in sediment samples. Two polycyclic
      musks, HHCB and AHTN, were dominant components in sediment, consistent with the
      use pattern of polycyclic musks by perfume industries in the Pearl River Delta
      region. The concentrations of total polycyclic musks ranged from 5.76 to 167
      microg/kg. Because of the large amount of domestic sewage and industrial
      wastewater discharged from the city of Guangzhou, the highest concentration of
      polycyclic musks was found in sediments from the Zhujiang River. The significant
      positive correlation between the HHCB to AHTN ratios and the concentrations of
      polycyclic musks suggested that the HHCB to AHTN ratio could be used as a tracer
      for source discrimination and for the degree of degradation in the environment.

PMID- 18092871
TI  - Induction of hepatic cytochrome P4501A1/2B activity and disruption of
      thyroglobulin synthesis/secretion by mono-ortho polychlorinated biphenyl and its
      hydroxylated metabolites in rat cell lines.
AB  - As the active metabolites of polychlorinated biphenyl (PCBs), hydroxylated
      polychlorinated biphenyls (OH-PCBs) are found in wildlife and human tissues. They
      have been proposed as main contributors for endocrine disruption of PCBs in
      living organisms. In this study, mono-ortho PCB 156 and its hydroxylated
      metabolites 4'-OH-PCB 159, 4'-OH-PCB 121, and 4'-OH-PCB 72 were selected to
      investigate the toxic effects on rat hepatoma H4IIE cell line and rat thyroid
      follicle FRTL-5 cell line at concentrations of 1, 10(2), 10(4) nM. 7
      Ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD)
      activities were determined with micro-EROD/PROD to indicate cytochrome P4501A1
      (CYP1A1) and cytochrome P4502B (CYP2B) induction in the H4IIE cell after exposure
      for 72 h. To assess thyroid disruption of these compounds, thyroglobulin
      concentrations also were detected inside FRTL-5 cell with immunocellularchemistry
      and in its medium with radioimmunoassay after exposure for 24 h. Significant
      inductions of EROD activity by PCB156 at 10(2) and 10(4) nM (p < 0.05) were
      observed, but no effects by the three OH-PCBs in H4IIE cell line. 7
      Pentoxyresorufin-O-dealkylase activities were induced only by 10(4) nM of PCB156
      and the three OH-PCBs (p < 0.05). Meanwhile, significant increases of
      thyroglobulin concentrations were observed in the medium of FRTL-5 cell exposed
      to 4'-OH-PCB 121 and 4'-OH-PCB 72 at all of the test concentrations (p < 0.05),
      but not to the other compounds. The results demonstrated that mono-ortho PCBs
      mainly could be metabolized to hydroxylated metabolites through CYP1A1 instead of
      CYP2B. Moreover, after being metabolized, OH-PCBs still sustained the ability to
      induce PROD activity and did exhibit the disruption on thyroglobulin
      synthesis/excretion in rat cells.

PMID- 18092872
TI  - Modeling polycyclic aromatic hydrocarbon composition profiles of sources and
      receptors in the Pear River Delta, China.
AB  - Changes in concentration profiles of polycyclic aromatic hydrocarbons (PAHs) from
      emission sources to various environmental media in the Pearl River Delta, China
      were investigated using fugacity modeling under steady state assumption. Both
      assumed evenly and observed unevenly distributed PAH moles emission profiles were
      applied. Applicability of the fugacity model was validated against the observed
      media PAH concentrations and profiles. At equal emission rates, the differences
      of media concentrations among various PAHs were as high as three (air) to seven
      (soil and sediment) orders of magnitude. Dramatic changes of PAH profiles from
      emission sources to various bulk environmental media also were demonstrated by
      using the actual emission rates. In general, the fractions of higher molecular
      weight PAHs in air and water were much lower than those at the emission sources,
      although the PAH profiles in soil and sediment were characterized by a
      significant reduction of lower molecular weight PAHs. It is likely that the field
      measured median concentration profiles cannot be adopted directly for source
      apportionment without rectification. The most influential parameters affecting
      PAH profiles in the study area were emission rates, degradation rates, adsorption
      coefficient, Henry's law constant, PAH concentrations in upstream surface water,
      fugacity ratio, vapor pressure, and diffusion coefficient in air.

PMID- 18092873
TI  - Distribution of persistent toxic substances in benthic bivalves from the inshore
      areas of the Yellow Sea.
AB  - A baseline survey of trace metals and organic pollutants in bivalves from the
      coastal areas of the Yellow Sea (China) showed the the concentrations of Cd and
      Pb in the bivalves from more than 85 and 73%, respectively, of the total sites
      (30 sites in all) exceeded the low limits of the national quality standards for
      marine organisms. At three sites, the contents of Cd in three species were even
      higher than the median limit, and a similar case with Pb occurred at another
      site. The tissue concentrations of As at four sites and of Hg at one site were
      above the low and the median limits, respectively, of the quality standards. At
      43% of all sites, the levels of petroleum hydrocarbons were higher than the low
      limit of the quality standards, and the tissue concentrations at two sites even
      went beyond the median limit at one site and the high limit at the other. The
      concentrations of phthalate esters and polycyclic aromatic hydrocarbons (PAHs) in
      the collected bivalves were not high, as shown by peak values of 305 and 302
      ng/g, respectively. The contents of polychlorinated biphenyls for all the species
      were much lower than the low limit of the quality standards. The compositional
      properties and isomeric ratios of PAHs indicated various pyrolytic procedures as
      the dominant origins. The sites with higher tissue contents of DDT and its
      metabolites (DDTs) over the low or the median quality limit were located mainly
      in the South Yellow Sea. The fractions and specific ratios of DDTs suggested that
      new inputs of DDT existed at two sites in the North Yellow Sea, and the potential
      sources involved technical DDT, technical dicofol, and their mixture.

PMID- 18092874
TI  - Semipermeable membrane device-assisted desorption of pyrene from soils and its
      relationship to bioavailability.
AB  - Desorption of pyrene from three different soils was studied using a semipermeable
      membrane device (SPMD)-assisted method to develop a new approach to predict
      bioavailability of hydrophobic organic compounds (HOCs) in soils. The results
      showed that pyrene desorption increased with reduction of soil organic matter
      content and elevation of pyrene concentration in unaged soils, and the 50-d
      desorption percentage was 52.2 +/- 3.6%, 76.3 +/- 1.5%, and 99.4 +/- 3.3% for
      soils 1, 2, and 3, respectively, at an initial pyrene concentration of 10 mg/kg
      and 73.6 +/- 4.9%, 94.1 +/- 4.1%, and 98.3 +/- 4.9%, respectively, at an initial
      pyrene concentration of 100 mg/kg. Aging led to a reduction in SPMD-assisted
      desorption because of movement of pyrene molecules from easy-desorbing to
      difficult-desorbing sites. The pyrene 50-d desorption percentage from 180-d-aged
      soils reduced to 5.8 +/- 0.6%, 18.8 +/- 0.9%, and 34.2 +/- 3.1% in soils 1, 2,
      and 3, respectively, at an initial pyrene concentration of 10 mg/kg and 43.9 +/-
      2.9%, 54.3 +/- 4.7%, and 86.3 +/- 3.5%, respectively, at an initial pyrene
      concentration of 100 mg/kg. Dry and wet conditions during aging had different
      effects on aging-derived reduction of pyrene desorption, which was found, to our
      knowledge for the first time, to depend on pollutant concentration. The water to
      soil ratio during desorption had a significant effect on SPMD-assisted desorption
      dynamics. When this ratio changed from 10:1 to 1:1, desorption dynamics became
      more linear and slower, because when the ratio was low, the SPMD could not
      contact with soil particles well and the diffusion of pyrene from pore water into
      the SPMD might become the limiting step for SPMD accumulation of pyrene from
      soils. Good correlations were found between SPMD-assisted desorption and the
      biota-soil accumulation factor for both unaged and aged soils. The SPMD-assisted
      desorption is considered to be a reliable approach to predict the bioavailability
      of HOCs in soils.

PMID- 18092875
TI  - Separation and aquatic toxicity of enantiomers of the pyrethroid insecticide
      lambda-cyhalothrin.
AB  - Chiral pollutants are receiving growing environmental concern due to differential
      biological activities of their enantiomers. In the present study, enantiomeric
      separation of the pyrethroid insecticide lambda-cyhalothrin (LCT) was
      investigated by high-performance liquid chromatography (HPLC) using the columns
      of Chiralpak AD (amylase tris[3,5-dimethyl-phenyl carbamate]), Chiralpak AS
      (amylase tris[(S)-1-phenyl carbamate]), Chiralcel OD (cellulose tris[3,5
      dimethylphenyl carbamate]), and Chiralcel OJ (cellulose tris[4-methyl benzoate])
      with different chiral stationary phases. The differential toxicities of the
      enantiomers in aquatic systems were evaluated using the acute zebrafish (Danio
      rerio) toxicity test and the zebrafish embryo test. The enantiomers of LCT were
      separated completely on all the columns tested and detected by circular dichroism
      at 236 nm. Better separations were achieved at lower temperatures (e.g., 20
      degrees C) and lower levels of polar modifiers (</=5%) in mobile phase. Ethanol
      was found to be a good modifier of the mobile phase for all the columns, although
      isopropanol acted better for the Chiralcel OD column. The (-)-enantiomer was >162
      times more toxic than its antipode to zebrafish in the acute test. The embryo
      test indicated that the exposure to LCT enantioselectively induced crooked body,
      yolk sac edema, and pericardial edema and that the (-)-enantiomer was 7.2 times
      stronger than the (+)-enantiomer in 96-h mortality. The malformations were
      induced by the racemate and its (-)-enantiomer at lower concentrations tested
      (e.g., 50 microg L(-1)), whereas the (+)-enantiomer induced malformations at
      relatively higher concentrations (>/=100 microg L(-1)). These results suggest
      that the toxicological effects of chiral pesticides must be evaluated using their
      individual enantiomers.

PMID- 18092876
TI  - Congener-specific distribution of polybrominated diphenyl ethers in fish of
      China: implication for input sources.
AB  - A total of 390 individual fish, including seven species of freshwater-farmed
      fish, three species of seawater-farmed fish, and three species of wild marine
      fish, from China were analyzed to determine the concentrations and congener
      distribution of polybrominated diphenyl ethers (PBDEs). The levels of
      Sigma(10)PBDEs (sum of BDEs 28, 47, 66, 100, 99, 85, 154, 153, 138, and 183) in
      seawater-farmed fish (median, 13.6 ng/g) were significantly higher than those in
      freshwater-farmed fish (median, 10.1 ng/g) and in wild marine fish (median, 4.5
      ng/g) on a lipid-weight basis. Lipid contents positively correlated with
      Sigma(10)PBDEs concentration (wet wt) in all fish species except for tilapia,
      bighead carp, bluntsnout bream, and common mullet; however, no significant
      relationship was found between fish length or weight and Sigma(10)PBDEs
      concentration except for one fish species. In general, BDE 47 was the dominant
      congener, with a mean contribution of 53.2%. Brominated diphenyl ether 209 was
      only detected in 14 samples, reflecting its low bioavailability or high degree of
      debromination. In addition, the ratios of BDE 47 to BDE 99 and of BDE 100 to BDE
      99 in freshwater-farmed fish were significantly higher than those in seawater
      farmed and wild marine fish. Freshwater-farmed fish had a relatively higher
      proportion of BDE 28, whereas seawater-farmed and wild marine fish contained more
      abundant BDE 66, BDE 100, and BDE 99. The difference in congener distribution
      might be indicative of different exposure pathways for PBDEs in three types of
      fish.

PMID- 18092877
TI  - Distribution of dissolved metals in seawater of Jinzhou Bay, China.
AB  - Based on the datum line survey in August 2005 and June and August of 2006, water
      samples were collected in 30 sites to examine the trend of spatial distribution
      and temporal change of dissolved metals in seawater of Jinzhou Bay, China. The
      results showed that copper (Cu), lead (Pb), zinc (Zn), and cadmium (Cd)
      concentrations ranged from 1.71 to 3.49, 0.38 to 1.19, 21.77 to 39.16, and 1.65
      to 2.01 microg/L, respectively. Except for Zn, the dissolved metal concentrations
      in August 2006 were much higher than those in August 2005. The concentrations in
      June 2006 were also higher than those in August 2006. The highest concentrations
      of dissolved metal were determined in samples collected from southwest of the Bay
      near sewage outfalls of Huludao Zinc Plant and Bohai Shipyard and the mouths of
      Wuli and Cishan rivers. The concentrations of dissolved metals increased inshore
      as compared with offshore. The principal contaminated factors were Zn, Cd, and Pb
      in the Jinzhou Bay. Significant positive correlations existed between the
      concentrations of Cu and Cd (0.016), as well as Zn and Cd (0.000). The overall
      results revealed that the Bohai Sea was one of the most contaminated areas by
      dissolved metals compared to other coastal areas in China.

PMID- 18092878
TI  - Residues of DDTs and their spatial distribution characteristics in soils from the
      Yangtze River Delta, China.
AB  - Organochlorine pesticides were used extensively in the Yangtze River Delta,
      China. However, knowledge about their residual levels and environmental fates in
      soils of this area is limited. This paper presents the residue isomers and
      spatial pattern of dichlorodiphenyltrichloroethane (DDT) in soils across 17 main
      cities in the Yangtze River Delta. Forty-three soil surface (0-15 cm) samples
      were collected during a field campaign conducted in October 2003 in the Delta.
      Six DDT isomers (1-[2-chlorophenyl]-1-[4-chlorophenyl]-2,2-dichloroethane [o,p'
      DDD], 1-[2-chlorophenyl]-1-[4-chlorophenyl]-2,2-dichloroethylene [o,p-'DDE],
      1,1,1-trichloro-2-[p-chlorophenyl]-2-[o-chlorophenyl]ethane [o,p'-DDT], p,p'
      dichlorodiphenyldichloroethane [p,p'-DDD], p,p'-dichlorodiphenyldichloroethylene
      [p,p'-DDE], p,p'-dichlorodiphenyltrichloroethane [p,p'-DDT]) were detected using
      gas chromatography. The results show that p,p'-DDE was the dominant isomer in the
      soil samples. The levels of DDT are generally low in soils of this area and are
      comparable to DDT levels in other cities in China and in soils from developed
      countries such as the United States and Germany. The isomer ratios of o,p'-DDT to
      p,p'-DDT and DDT to (DDD + DDE) were employed to identify the source of DDT. The
      computed ratios implied that the source of DDT might be related to the
      application of dicofol, an acaricide manufactured from technical DDTs and mainly
      used on cotton fields to treat mites.

PMID- 18092879
TI  - Inhibitory effects of atrazine on Chlorella vulgaris as assessed by real-time
      polymerase chain reaction.
AB  - Atrazine, a highly toxic herbicide, is frequently detected in surface water
      because of its heavy application. Algae are among the aquatic organisms most
      susceptible to atrazine pollution in water. In the present study, the aquatic
      alga Chlorella vulgaris Beijerinck was chosen to assess the acute toxicity of
      atrazine (48-96 h) in terms of gene transcription and physiological changes. A
      real-time polymerase chain reaction (PCR) assay was used to quantify transcript
      levels of three photosystem genes in C. vulgaris. The diel patterns for
      regulation of the psaB (photosystem I reaction center protein subunit B), psbC
      (an integral membrane protein component of photosystem II), and rbcL (large
      subunit of ribulose-1,5-bisphosphate carboxylase oxygenase) gene transcripts were
      successfully quantified. Results showed that atrazine reduced the transcript
      abundances of three target genes and that the abundances decreased with
      increasing atrazine concentration. The determined smallest transcript levels of
      psaB, psbC, and rbcL, which occurred at the highest atrazine concentration tested
      (400 mug/L), were only 34.6, 34.6, and 8.1%, respectively, of the control sample
      value. Exposure to atrazine increased the level of malondialdehyde by 1.74-fold
      (the highest value) in C. vulgaris, suggesting potential oxidative damage to the
      alga. The activities of antioxidation enzymes (e.g., superoxide dismutase,
      peroxidase, and catalase) also increased markedly in the presence of atrazine,
      with maximum increases of 1.82-, 1.59-, and 2.31-fold, respectively. These
      elevated activities may help to alleviate the oxidative damage. Our results
      demonstrate that atrazine is highly toxic to this alga and that real-time PCR is
      an efficient technique for assessing the toxicity of xenobiotic compounds in
      algae.

PMID- 18092880
TI  - Release of adsorbed polycyclic aromatic hydrocarbons under cosolvent treatment:
      implications for availability and fate.
AB  - During laboratory and field studies, a fraction of contaminants in soils or
      sediments often is observed to be highly resistant to desorption. This desorption
      resistant fraction may have significant effects on long-term fate and exposure of
      soil/ sediment-bound contaminants in particular, causing much reduced
      availability and contaminant persistence. Previous work by many research groups
      has indicated that this nonideal desorption behavior could be better predicted
      with biphasic desorption models. The present study further investigated the
      release of naphthalene and phenanthrene from sediments during and after cosolvent
      treatment. Experimental results indicate that release of these two compounds
      under cosolvent conditions can be accurately predicted with a previously
      developed, biphasic desorption model when the solubility enhancement effect of
      cosolvent is accounted for using standard activity coefficient ratios. In
      addition, desorption of the residual contaminants after cosolvent treatment
      follows the original biphasic desorption model very well, suggesting that
      cosolvent treatment increases only the aqueous solubility and has little effect
      on the nature of the desorption-resistant fraction and that cosolvent desorption
      is a valuable analytical tool for quickly measuring the magnitude of the
      desorption-resistant fraction. The present findings might have important
      implications for the mechanisms controlling resistant desorption of hydrophobic
      organic compounds and for predicting the availability and long-term fate of
      contaminants in soils and sediments.

PMID- 18092881
TI  - Environmental science and research in China: a snapshot of the current state.

PMID- 18092884
TI  - Detection of intracellular bacterial communities in human urinary tract
      infection.
AB  - BACKGROUND: Urinary tract infections (UTIs) are one of the most common bacterial
      infections and are predominantly caused by uropathogenic Escherichia coli (UPEC).
      While UTIs are typically considered extracellular infections, it has been
      recently demonstrated that UPEC bind to, invade, and replicate within the murine
      bladder urothelium to form intracellular bacterial communities (IBCs). These IBCs
      dissociate and bacteria flux out of bladder facet cells, some with filamentous
      morphology, and ultimately establish quiescent intracellular reservoirs that can
      seed recurrent infection. This IBC pathogenic cycle has not yet been investigated
      in humans. In this study we sought to determine whether evidence of an IBC
      pathway could be found in urine specimens from women with acute UTI. METHODS AND
      FINDINGS: We collected midstream, clean-catch urine specimens from 80 young
      healthy women with acute uncomplicated cystitis and 20 asymptomatic women with a
      history of UTI. Investigators were blinded to culture results and clinical
      history. Samples were analyzed by light microscopy, immunofluorescence, and
      electron microscopy for evidence of exfoliated IBCs and filamentous bacteria.
      Evidence of IBCs was found in 14 of 80 (18%) urines from women with UTI.
      Filamentous bacteria were found in 33 of 80 (41%) urines from women with UTI.
      None of the 20 urines from the asymptomatic comparative group showed evidence of
      IBCs or filaments. Filamentous bacteria were present in all 14 of the urines with
      IBCs compared to 19 (29%) of 66 samples with no evidence of IBCs (p < 0.001). Of
      65 urines from patients with E. coli infections, 14 (22%) had evidence of IBCs
      and 29 (45%) had filamentous bacteria, while none of the gram-positive infections
      had IBCs or filamentous bacteria. CONCLUSIONS: The presence of exfoliated IBCs
      and filamentous bacteria in the urines of women with acute cystitis suggests that
      the IBC pathogenic pathway characterized in the murine model may occur in humans.
      The findings support the occurrence of an intracellular bacterial niche in some
      women with cystitis that may have important implications for UTI recurrence and
      treatment.

PMID- 18092885
TI  - Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed
      against the Duffy binding protein.
AB  - BACKGROUND: Plasmodium vivax invasion requires interaction between the human
      Duffy antigen on the surface of erythrocytes and the P. vivax Duffy binding
      protein (PvDBP) expressed by the parasite. Given that Duffy-negative individuals
      are resistant and that Duffy-negative heterozygotes show reduced susceptibility
      to blood-stage infection, we hypothesized that antibodies directed against region
      two of P. vivax Duffy binding protein (PvDBPII) would inhibit P. vivax invasion
      of human erythrocytes. METHODS AND FINDINGS: Using a recombinant region two of
      the P. vivax Duffy binding protein (rPvDBPII), polyclonal antibodies were
      generated from immunized rabbits and affinity purified from the pooled sera of 14
      P. vivax-exposed Papua New Guineans. It was determined by ELISA and by flow
      cytometry, respectively, that both rabbit and human antibodies inhibited binding
      of rPvDBPII to the Duffy antigen N-terminal region and to Duffy-positive human
      erythrocytes. Additionally, using immunofluorescent microscopy, the antibodies
      were shown to attach to native PvDBP on the apical end of the P. vivax merozoite.
      In vitro invasion assays, using blood isolates from individuals in the Mae Sot
      district of Thailand, showed that addition of rabbit anti-PvDBPII Ab or serum
      (antibodies against, or serum containing antibodies against, region two of the
      Plasmodium vivax Duffy binding protein) (1:100) reduced the number of parasite
      invasions by up to 64%, while pooled PvDBPII antisera from P. vivax-exposed
      people reduced P. vivax invasion by up to 54%. CONCLUSIONS: These results show,
      for what we believe to be the first time, that both rabbit and human antibodies
      directed against PvDBPII reduce invasion efficiency of wild P. vivax isolated
      from infected patients, and suggest that a PvDBP-based vaccine may reduce human
      blood-stage P. vivax infection.

PMID- 18092887
TI  - Communal living by bacteria and the pathogenesis of urinary tract infections.

PMID- 18092886
TI  - Daily dosing of rifapentine cures tuberculosis in three months or less in the
      murine model.
AB  - BACKGROUND: Availability of an ultra-short-course drug regimen capable of curing
      patients with tuberculosis in 2 to 3 mo would significantly improve global
      control efforts. Because immediate prospects for novel treatment-shortening drugs
      remain uncertain, we examined whether better use of existing drugs could shorten
      the duration of treatment. Rifapentine is a long-lived rifamycin derivative
      currently recommended only in once-weekly continuation-phase regimens.
      Moxifloxacin is an 8-methoxyfluoroquinolone currently used in second-line
      regimens. METHODS AND FINDINGS: Using a well-established mouse model with a high
      bacterial burden and human-equivalent drug dosing, we compared the efficacy of
      rifapentine- and moxifloxacin-containing regimens with that of the standard daily
      short-course regimen based on rifampin, isoniazid, and pyrazinamide. Bactericidal
      activity was assessed by lung colony-forming unit counts, and sterilizing
      activity was assessed by the proportion of mice with culture-positive relapse
      after 2, 3, 4, and 6 mo of treatment. Here, we demonstrate that replacing
      rifampin with rifapentine and isoniazid with moxifloxacin dramatically increased
      the activity of the standard daily regimen. After just 2 mo of treatment, mice
      receiving rifapentine- and moxifloxacin-containing regimens were found to have
      negative lung cultures, while those given the standard regimen still harbored
      3.17 log10 colony-forming units in the lungs (p < 0.01). No relapse was observed
      after just 3 mo of treatment with daily and thrice-weekly administered
      rifapentine- and moxifloxacin-containing regimens, whereas the standard daily
      regimen required 6 mo to prevent relapse in all mice. CONCLUSIONS: Rifapentine
      should no longer be viewed solely as a rifamycin for once-weekly administration.
      Our results suggest that treatment regimens based on daily and thrice-weekly
      administration of rifapentine and moxifloxacin may permit shortening the current
      6 mo duration of treatment to 3 mo or less. Such regimens warrant urgent clinical
      investigation.

PMID- 18092888
TI  - Towards a vaccine against Plasmodium vivax malaria.

PMID- 18092889
TI  - Transglutaminase 2 undergoes a large conformational change upon activation.
AB  - Human transglutaminase 2 (TG2), a member of a large family of enzymes that
      catalyze protein crosslinking, plays an important role in the extracellular
      matrix biology of many tissues and is implicated in the gluten-induced
      pathogenesis of celiac sprue. Although vertebrate transglutaminases have been
      studied extensively, thus far all structurally characterized members of this
      family have been crystallized in conformations with inaccessible active sites. We
      have trapped human TG2 in complex with an inhibitor that mimics inflammatory
      gluten peptide substrates and have solved, at 2-A resolution, its x-ray crystal
      structure. The inhibitor stabilizes TG2 in an extended conformation that is
      dramatically different from earlier transglutaminase structures. The active site
      is exposed, revealing that catalysis takes place in a tunnel, bridged by two
      tryptophan residues that separate acyl-donor from acyl-acceptor and stabilize the
      tetrahedral reaction intermediates. Site-directed mutagenesis was used to
      investigate the acyl-acceptor side of the tunnel, yielding mutants with a marked
      increase in preference for hydrolysis over transamidation. By providing the
      ability to visualize this activated conformer, our results create a foundation
      for understanding the catalytic as well as the non-catalytic roles of TG2 in
      biology, and for dissecting the process by which the autoantibody response to TG2
      is induced in celiac sprue patients.

PMID- 18092890
TI  - Basic math in monkeys and college students.
AB  - Adult humans possess a sophisticated repertoire of mathematical faculties. Many
      of these capacities are rooted in symbolic language and are therefore unlikely to
      be shared with nonhuman animals. However, a subset of these skills is shared with
      other animals, and this set is considered a cognitive vestige of our common
      evolutionary history. Current evidence indicates that humans and nonhuman animals
      share a core set of abilities for representing and comparing approximate
      numerosities nonverbally; however, it remains unclear whether nonhuman animals
      can perform approximate mental arithmetic. Here we show that monkeys can mentally
      add the numerical values of two sets of objects and choose a visual array that
      roughly corresponds to the arithmetic sum of these two sets. Furthermore,
      monkeys' performance during these calculations adheres to the same pattern as
      humans tested on the same nonverbal addition task. Our data demonstrate that
      nonverbal arithmetic is not unique to humans but is instead part of an
      evolutionarily primitive system for mathematical thinking shared by monkeys.

PMID- 18092891
TI  - Molecular cartography: mapping the landscape of meiotic recombination.

PMID- 18092892
TI  - Out FOXing Parkinson disease: where development meets neurodegeneration.

PMID- 18092894
TI  - Viewpoint: a conversation with Mark Dignan, by M Christine Nagy, and Jeffrey S
      Hallam.

PMID- 18092895
TI  - Family factors as correlates of diet in relatives of colon cancer patients.
AB  - OBJECTIVES: To examine family social support and closeness to the patient for
      their association with diet in first-degree relatives (FDRs) of colon cancer
      patients. METHODS: Participants (N=98) were interviewed by telephone to assess
      study constructs. Multiple hierarchical regressions examined relationships among
      family factors and diet. RESULTS: Family social support was associated with
      healthier diets, particularly fruits and vegetables. However, FDRs closest to the
      cancer patient had less healthy diets. CONCLUSIONS: FDRs with close relationships
      to their family member with cancer may be in greatest need of dietary
      intervention. Diet is understudied in this high-risk population and warrants more
      investigation.

PMID- 18092896
TI  - The transtheoretical model and exercise among individuals living with HIV.
AB  - OBJECTIVE: To examine the distribution of the stages of change for exercise among
      individuals living with HIV as well as to identify the differences between the
      transtheoretical model (TTM) constructs. METHODS: Cross-sectional self-report
      data were collected from 208 individuals accessing HIV-related care services.
      RESULTS: More than half of the sample was in the action and maintenance stages,
      indicating a higher level of physical activity in this sample than the general
      population. Furthermore, the patterns of the TTM constructs across stages were
      consistent with past research. CONCLUSIONS: Stage-matched TTM interventions can
      be developed for individuals living with HIV.

PMID- 18092897
TI  - Effectiveness evaluation of the N-O-T smoking cessation program for adolescents.
AB  - OBJECTIVE: To evaluate the effectiveness of the Not-On-Tobacco Program. METHODS:
      Forty-four high schools implemented the program (n=241 students), with 27
      comparison schools (n=251 students). Students reported smoking in the last 7 and
      30 days at baseline and follow-up. RESULTS: Those in the program had an increased
      likelihood of reporting 30-day abstinence at end of program (OR = 4.2) but not at
      6 or 12 months. For 7-day abstinence there was no significant difference for any
      time point. CONCLUSIONS: In this effectiveness evaluation the N-O-T Program
      increased quitting during the program, but the effects were not present at 6 or
      12 months.

PMID- 18092898
TI  - An instrument to assess the obesogenic environment of child care centers.
AB  - OBJECTIVES: To describe protocol and interobserver agreements of an instrument to
      evaluate nutrition and physical activity environments at child care. METHODS:
      Interobserver data were collected from 9 child care centers, through direct
      observation and document review (17 observer pairs). RESULTS: Mean agreement
      between observer pairs was 87.26% and 79.29% for the observation and document
      review, respectively. Items with lower agreement were primarily staff behavior,
      counting across the day/week, and policy classifications. CONCLUSIONS: Although
      some revisions are required, the interobserver agreement for the environment and
      policy assessment and observation (EPAO instrument) appears to be quite good for
      assessing the nutrition and physical activity environment of child care centers.

PMID- 18092899
TI  - How to improve adolescents' sun protection behavior? Age and gender issues.
AB  - OBJECTIVE: To explore adolescents' self-reported reasons for sun protection, as
      adolescents as a group continue to have poor sun protection practices. METHODS:
      Seventeen age- and gender-segregated focus groups were conducted in Australian
      high schools. RESULTS: Reasons for using sun protection included personal
      comfort, appearance, policies, fear of skin cancer, expectations of authority
      figures, peer actions, and habit. Reasons for not using sun protection included
      desire for a tan, inconvenience, low perceived risk, and fashion. Age and gender
      effects were found. CONCLUSIONS: Avenues for intervention with adolescents
      include authority figures, peer advocacy, the fashion industry, and improved sun
      protection products.

PMID- 18092900
TI  - Middle school students' perceived access to cigarettes in Virginia.
AB  - OBJECTIVE: To examine correlates of perceived access to cigarettes at home,
      school, and the store among youth. METHODS: Virginia middle school youth were
      surveyed before beginning tobacco prevention programs. Multivariate analyses
      examined household smoking, peer smoking, and perceived community tobacco use for
      their relationship to perceived access at home, school, and the store. RESULTS:
      Perceived access at home was associated with parent, sibling, and friend smoking.
      Perceived access at school and stores was associated with perceived peer and
      community smoking. CONCLUSIONS: Youth tobacco prevention programs should target
      the commercial and social sources of tobacco access to reduce experimentation,
      adoption, and addiction among youth.

PMID- 18092901
TI  - Drink specials and the intoxication levels of patrons exiting college bars.
AB  - OBJECTIVES: To determine whether drink specials independently increase patrons'
      risk of achieving a high level of intoxication upon exiting drinking
      establishments. METHODS: In a campus community, data were collected from exiting
      patrons (N=291) via sidewalk interviews and breath tests on 6 nights of 2
      consecutive semesters. RESULTS: A multivariate model revealed that taking
      advantage of a drink special was associated with a fourfold increase in risk of
      achieving a BAC >or= 80 mg/dl. CONCLUSIONS: These findings are the first to
      document that the drink discounting practices of college bars can be linked to
      higher intoxication levels among exiting patrons.

PMID- 18092902
TI  - Social context of drinking and alcohol problems among college students.
AB  - OBJECTIVE: To examine how social contexts of drinking are related to alcohol use
      disorders, other alcohol-related problems, and depression among college students.
      METHODS: Logistic regression models controlling for drinking frequency measured
      the association between social context and problems, among 728 current drinkers.
      RESULTS: Drinking for social facilitation was associated with drinking and
      driving and housing violations. Drinking in the context of motor vehicles was
      associated with alcohol abuse/ dependence. Drinking in a context of emotional
      pain was associated with clinical depression. CONCLUSIONS: Alcohol-free
      programming that fulfills needs for conviviality and addresses early signs of
      depression might reduce alcohol problems among college students.

PMID- 18092903
TI  - Consumer awareness and attitudes related to new potential reduced-exposure
      tobacco products.
AB  - OBJECTIVE: To assess US consumers' awareness of potential reduced-exposure
      tobacco products (PREPs) and correlates of interest in these products. METHODS: A
      representative sample of 9,736 US consumers who had responded to a previous
      marketing survey were queried in 2005. RESULTS: Among current smokers, interest
      in PREPs was high (77.3%) and was associated with concern about personal health
      as well as favorable attitudes towards technology and a willingness to experiment
      with new products and trends. CONCLUSIONS: These results suggest that interest in
      PREPs may reflect a range of consumer preferences beyond expectations of health
      benefit.

PMID- 18092904
TI  - Prevalence of tobacco use among students aged 13-15 years in the South-Eastern
      Europe health network.
AB  - OBJECTIVE: To examine adolescent tobacco use among members of the South-Eastern
      Europe (SEE) Health Network using data from the Global Youth Tobacco Survey
      (GYTS). METHODS: Nationally representative samples were drawn from students in
      grades associated with youth aged 13 to 15 in Albania, Bosnia and Herzegovina,
      Bulgaria, Croatia, the Former Yugoslavian Republic of Macedonia, Montenegro,
      Republic of Moldova, Romania, and Serbia. RESULTS: Current cigarette smoking
      rates among students ranged from 5.6% to 33.1%. Current use of tobacco products
      other than cigarettes ranged from 3.6% to 10.2%. CONCLUSIONS: If effective
      programs are not developed, implemented, and enforced, morbidity and mortality
      attributed to tobacco use will surely increase.

PMID- 18092905
TI  - HLA homozygous stem cell lines derived from human parthenogenetic blastocysts.
AB  - Individual HLA homozygous parthenogenetic human stem cell (hpSC-Hhom) lines have
      the potential for cell-based therapy in a significant number of individuals,
      provided the HLA haplotype is prevalent. We report the successful derivation of
      four stable hpSC-Hhom lines from both HLA homozygous and HLA heterozygous donors.
      Of these, the hpSC-Hhom-4 line carries the HLA haplotype found most commonly
      within the U.S. population, and is shared by different racial groups. These hpSC
      Hhom lines demonstrate typical human embryonic stem cell morphology, expressing
      appropriate stem cell markers and possessing high levels of alkaline phosphatase
      and telomerase activity. Additionally, injection of these cell lines into
      immunodeficient animals leads to teratoma formation. G-banded karyotyping
      demonstrates a normal 46,XX karyotype in lines hpSC-Hhom-1 and hpSC-Hhom-4, and
      chromosomal anomalies in lines hpSC-Hhom-2 and hpSC-Hhom-3, both derived from the
      same donor. HLA genotyping of all four hpSC-Hhom lines demonstrates that they are
      HLA homozygous. Furthermore, in the case of HLA heterozygous donors, the hpSC
      Hhom lines inherit the haplotype from only one of the donor's parents. Single
      nucleotide polymorphism (SNP) data analysis suggests that hpSC-Hhom lines derived
      from HLA heterozygous oocyte donors are homozygous throughout the genome as
      assessed by SNP analysis. The protocol used for deriving these HLA homozygous
      stem cell lines minimizes the use of animal-derived components, which makes them
      more appealing for potential clinical application.

PMID- 18092907
TI  - Fine mapping of mouse QTLs for fatness using SNP data.
AB  - Quantitative trait loci (QTLs), as determined in crossbred studies, are a
      valuable resource to identify genes responsible for the corresponding phenotypic
      variances. Due to their broad chromosomal extension of some dozens of megabases,
      further steps are necessary to bring the number of candidate genes that underlie
      the detected effects to a reasonable order of magnitude. We use a set of 13,370
      SNPs to identify informative haplotype blocks in 22 mouse QTLs for fatness. About
      half of the genes in a typical QTL overlap with haplotype blocks, which are
      different for the two base mouse lines, and which, thus, qualify for further
      analysis. For these genes we collect four more pieces of evidence for association
      with fat accumulation, namely (1) homology to genes identified in a
      Caenorhabditis elegans knock-out experiment as fat decreasing or fat increasing,
      (2) the overexpression of the genes in mouse fat, liver, muscle, or hypothalamus
      tissues, (3) the occurrence of a gene in several independently found QTLs, and
      (4) the information provided by gene ontology, to achieve a ranked list of 131
      candidate genes. Ten genes fulfill three or four of the above sketched criteria
      and are discussed briefly, 121 further genes fulfilling two criteria are provided
      as on-line material. Viewing the genomic region of fatness-related QTLs under
      several different aspects is appropriate to assess the many thousands of genes
      that reside in such QTLs and to produce lists of more robust candidate genes.

PMID- 18092906
TI  - Implementation of microarrays for Methylobacterium extorquens AM1.
AB  - Microarrays are an important tool for understanding global gene expression
      changes, and the resulting data sets can be used to direct physiologic and
      metabolic studies. To take advantage of this technology, 60-mer oligonucleotide
      microarrays were designed for Methylobacterium extorquens AM1 to study gene
      expression changes that occur under differing physiological conditions. The
      carbon utilization pathways for methanol and succinate have been well
      characterized, and growth with these substrates was chosen as the condition used
      to validate the microarray data. The data were analyzed using two different
      methods and compared to previously obtained experimental data. The array data
      processed using the Significance Analysis of Microarrays followed by p-value
      assessment, correlated best to the experimental data. In addition to validating
      the microarrays, these studies uncovered possible connections between
      methylotrophy, iron, and sulfur homeostasis, bacteriochlorophyll production and
      polyketide synthesis, and will likely aid in uncovering further metabolic
      networks and genes required for methylotrophy.

PMID- 18092908
TI  - Experiment-specific estimation of peptide identification probabilities using a
      randomized database.
AB  - Determining the error rate for peptide and protein identification accurately and
      reliably is necessary to enable evaluation and crosscomparisons of high
      throughput proteomics experiments. Currently, peptide identification is based
      either on preset scoring thresholds or on probabilistic models trained on
      datasets that are often dissimilar to experimental results. The false discovery
      rates (FDR) and peptide identification probabilities for these preset thresholds
      or models often vary greatly across different experimental treatments, organisms,
      or instruments used in specific experiments. To overcome these difficulties,
      randomized databases have been used to estimate the FDR. However, the cumulative
      FDR may include low probability identifications when there are a large number of
      peptide identifications and exclude high probability identifications when there
      are few. To overcome this logical inconsistency, this study expands the use of
      randomized databases to generate experiment-specific estimates of peptide
      identification probabilities. These experiment-specific probabilities are
      generated by logistic and Loess regression models of the peptide scores obtained
      from original and reshuffled database matches. These experiment-specific
      probabilities are shown to very well approximate "true" probabilities based on
      known standard protein mixtures across different experiments. Probabilities
      generated by the earlier Peptide_Prophet and more recent LIPS models are shown to
      differ significantly from this study's experiment-specific probabilities,
      especially for unknown samples. The experiment-specific probabilities reliably
      estimate the accuracy of peptide identifications and overcome potential logical
      inconsistencies of the cumulative FDR. This estimation method is demonstrated
      using a Sequest database search, LIPS model, and a reshuffled database. However,
      this approach is generally applicable to any search algorithm, peptide scoring,
      and statistical model when using a randomized database.

PMID- 18092909
TI  - Proteasome activity deregulation in LEC rat hepatitis: following the insights of
      transcriptomic analysis.
AB  - LEC rats show spontaneous hepatitis and hepatocarcinoma development related to
      oxidative stress due to abnormal copper accumulation in the liver. We used DNA
      microarrays bearing 22,012 genes to investigate at the transcriptomic level the
      progression of the hepatitis in LEC rats in comparison to a control obtained from
      LEC rats treated with D-penicillamine, a copper chelating agent known to block
      hepatitis development. Multivariate statistical analyses as partial least square
      (PLS) regression between transcriptomic data and hepatitis markers in plasma led
      us to select 483 genes related to hepatitis development in these rats. After a
      complementary discriminant analysis (PLS-DA), 239 important genes for the
      separation between the different rat groups were selected. Gene ontology
      classification revealed an overrepresentation of genes involved in protein
      metabolism-related functions. More importantly, some genes implicated in
      proteasome pathway were upregulated. However, analysis of 20S proteasome activity
      showed that trypsin-like and peptidylglutamyl peptide hydrolase activities were
      diminished during hepatitis. Because oxidative stress is known to promote the
      inactivation of the proteasome complex, we propose the deregulation of the
      proteasome genes expression as a result of oxidative inactivation of proteasome
      activity during hepatitis in LEC rats. These results bring new insights in the
      hepatitis and the hepatocarcinogenesis development.

PMID- 18092910
TI  - A subset of skin-expressed microRNAs with possible roles in goat and sheep hair
      growth based on expression profiling of mammalian microRNAs.
AB  - The microRNAs (miRNAs) are an extensive class of small noncoding RNAs (18-25
      nucleotides) with probable roles in the regulation of gene expression. Due to the
      fact that miRNAs are conserved in closely related eukaryotes and some are also
      conserved across a larger evolutionary distance, their potential functions in
      mammalian development are under active study. In order to identify mammalian
      miRNAs that might function in hair growth, we characterized the expression of 159
      miRNAs in adult body side skin and ear skin from goat and sheep using microarray
      analysis. Of these, 19 miRNAs were specifically expressed or greatly enriched in
      body side skin in goats and sheep. This suggests hair growth-specific functions
      for miRNAs. Of the coexpressed 105 miRNAs, the degree of correlation within
      species is higher than interspecies. Nine of the expressed miRNAs were detected
      exclusively in the goat body side skin area where more cashmere was grown than
      coat hair; mmu-miR-720 and mmu-miR-199b were expressed primarily in goat skin.
      The identification of 105 of skin-expressed miRNAs whose expression behavior is
      conserved in goats and sheep differentiating hair follicles implicates these
      miRNAs have functions in mammalian hair follicles growth and development. We
      demonstrate that miRNAs previously associated with hair follicles in the mouse
      are also expressed in the adult skin of goats and sheep. In addition, 69 more
      conserved miRNAs cross-species were discerned in the study. Of them, the let-7,
      mir-17, mir-30, mir-15, and mir-8 gene families were expressed in high frequency.
      These results reveal critical roles of them in skin and hair follicle development
      and function.

PMID- 18092911
TI  - Constructing human transcriptional regulatory subnets from crossgenome comparison
      and gene expression profile analysis.
AB  - With the completion of Human Genome Project (HGP), understanding the complex
      interaction between trans- and cis-regulatory elements comprehensively and
      identifying these potential functional elements are fundamental problems in
      functional genomics. Although many computational approaches have been developed
      for lower eukaryotes and prokaryotes, most of them often do not generalize to
      vertebrates. Here, we use a decay function to characterize transcriptional
      behavior, and analyze correlations on gene expression profiles of human and mouse
      to construct coregulated gene groups. Using these two closely related species, we
      perform comparative genome analysis and identify target genes and conserved
      functional cis-regulatory elements by motif overrepresentation. Moreover, we
      presented experimental evidences (ChIP-Chip) for E2F to assert our findings.

PMID- 18092912
TI  - Comparative approaches to the investigation of responses to stress and viral
      infection in cattle.
AB  - Fatal bovine respiratory disease (BRD) is a major cause of financial losses in
      the cattle industry. A variety of stressors have been implicated as contributing
      to disease severity. However, it has proven difficult to determine the role these
      individual factors may play in the final outcome of this disease complex. The
      objective of the present investigation was to obtain proteomic, metabonomic, and
      elemental profiles of bovine serum samples from stressed and control animals
      before and after a primary viral infection to determine if these profiles could
      distinguish between responses to stressors and viral infection. Multivariate
      analysis revealed distinct differential trends in the distribution profile of
      proteins, metabolites, and elements following a stress response both before and
      after primary viral infection. A group of acute phase proteins, metabolites, and
      elements could be specifically linked to either a stress response (decreased
      serum amyloid A and Cu, increased apolipoprotein CIII, amino acids, LDL, P, and
      Mo) or a primary viral respiratory infection (increased apolipoprotein A1,
      haptoglobin, glucose, amino acids, LDL and Cu, decreased Lipid, and P). Thus,
      combined OMICS analysis of serum samples revealed that multimethod analysis could
      be used to discriminate between the complex biological responses to stress and
      viral infection.

PMID- 18092914
TI  - An innovative model for conducting a participatory community health assessment.
AB  - Understanding a community's perceived health care needs is essential to the
      promotion of community health. The purpose of this article is to review various
      methodologies used to assess community health care needs, and then provide a case
      example of a transcultural exploration of perceived health care needs of the
      residents of Utila, Honduras. This study presents a template for using unique
      assessment tools to empower communities to identify their health care needs.
      Implications for future transcultural community nursing studies are discussed.

PMID- 18092915
TI  - The experience of having become sexually active for teen mothers.
AB  - The purpose of this phenomenological study was to describe teen mothers'
      experience of having become sexually active. Most scholars who have studied teen
      sexual behavior have used quantitative methods and measured constructs such as
      self-esteem. Prior to data-gathering, literature about teen sexual behavior was
      reviewed and set aside to enable a more direct focus on data. Parental consent
      for participation was obtained for participants under 18. Of the 10 participants
      (aged 16 to 19 years), all had at least one living child. Each participant took
      part in 3 audiotaped interviews. Data about perceptions, actions, and intentions
      were compared across each participant's interviews and interviews of all
      participants. Four phenomena were discerned as ways in which participants had
      structured their experiences: (a) making a safe place, (b) redefining myself, (c)
      creating my own life story, and (c) engaging with the unknown. Compared to prior
      literature, the phenomena offer a richer and deeper perspective on teen sexual
      behavior. Findings suggest that efforts to increase perceptions of safety, to
      support personal identity, to bolster creativity, and to offer exploratory
      opportunities beyond sexual encounters could enhance effectiveness of programs
      designed to prevent early-onset sexual activity.

PMID- 18092916
TI  - Development, implementation and evaluation of a new adult asthma self-management
      program.
AB  - The purpose of the research was to develop, implement, and evaluate a new adult
      asthma self-management program with a multidisciplinary perspective. Small groups
      of adults met for 2 hr for 7 consecutive weekly meetings. Participants were asked
      to practice asthma specific behaviors (including peak expiratory flow monitoring,
      avoidance/removal of asthma triggers, and controller medication adherence) and
      general lifestyle behaviors (including drinking water, practicing relaxation,
      washing hands, and exercising). Learner-centered teaching techniques such as
      interactive communication and social support were utilized to help participants
      practice self-management behaviors including problem-solving and goal-setting.
      Paired sample t-tests included statistically significant improvements in asthma
      knowledge, asthma specific quality of life (QOL), asthma specific behaviors such
      as peak flow monitoring and general life style behaviors such as frequency of
      daily exercise. These results provide evidence that this new adult asthma self
      management program can lead to both knowledge acquisition and behavioral changes.

PMID- 18092917
TI  - Health-related quality of life in low-income older African Americans.
AB  - This study examined the relationships among comorbid conditions, symptom stress,
      depression, functional status and health-related quality of life (HRQOL) in low
      income older African Americans with chronic diseases. A convenience sample of 83
      older African American adults living in subsidized housing for elders
      participated in the study. Data were collected in face-to-face interviews.
      Participants reported lower scores on HRQOL than the SF-36 norms for age 60 or
      older in the general U.S. population. Comorbid conditions, symptom distress,
      depression, and functional status significantly predicted both the physical (F =
      38.92, p < .001) and mental (F = 23.21, p < .001) health components of HRQOL,
      accounting for 63% of variance in the SF-36 physical health score and 55% of the
      variance in the SF-36 mental health score. The findings suggested that developing
      interventions to assist older African Americans to better manage their symptoms
      and depression are of prime importance for improving HRQOL.

PMID- 18092920
TI  - Induction of transgene-specific cytotoxic T lymphocyte responses after
      transplantation of gene-modified CD34+ cells despite nonablative
      immunosuppressive conditioning.
AB  - In previous studies we showed that low-dose irradiation and immunosuppression
      with cyclosporine and mycophenolate mofetil prolonged in vivo persistence of gene
      modified T cells but was unable to induce tolerance. We hypothesized that the
      lack of sustained antigen presentation because of the limited life span of the
      infused T cells might be responsible for the lack of tolerance induction. Thus,
      we examined whether tolerance could be induced by infusion of long-lived stem
      cells. Two baboons were transplanted with YFP/neo-transduced CD34+ cells. The
      transgene-marked cells disappeared completely within 5 weeks and CD8+ transgene
      specific cytotoxic T lymphocytes were detected in both animals. Thus, this
      nonablative conditioning regimen did not provide sufficient immunosuppression for
      the induction of tolerance after infusion of gene-modified CD34+ cells.

PMID- 18092921
TI  - Impact of retroviral vector components stoichiometry on packaging cell lines:
      effects on productivity and vector quality.
AB  - The productivity of retroviral vector producer cell lines is currently low; this
      can be attributed partly to disruption of the viral components stoichiometry
      originated by the dissociation of gag-pol, env, and viral genome. This paper
      addresses the impact of viral components stoichiometry on cell productivity and
      vector quality (vector stability and transduction efficiency). A strategy is
      proposed for the development of packaging cell lines allowing for stoichiometric
      optimization of viral components. This strategy is based on the introduction of a
      transgene in the first step of cell line development, thus making it possible to
      eliminate transgene limitations and therefore exploring maximal infectious
      productivity based on the levels of expression of Gag-Pol and envelope. The
      transgene can subsequently be exchanged for a gene of interest, using site
      specific flipase/flipase recombination target (Flp/FRT) cassette replacement. It
      was observed that Gag-Pol controlled the order of magnitude of infectious titer:
      a small, 2-fold variation in its expression could result in a 10- to 100-fold
      improvement in infectious titer; the RNA transgene and envelope expression
      limitations had a lower impact. The ratios of retroviral components strongly
      affected cell productivity but did not affect vector stability; however,
      transduction efficiencies were affected by an imbalanced ratio of the components,
      resulting in the production of higher amounts of defective virus. Thus,
      stoichiometric optimization of viral components not only improves cell
      productivity but also increases vector quality.

PMID- 18092919
TI  - Advances in microRNAs: implications for gene therapists.
AB  - MicroRNAs (miRNAs) are a class of small regulatory RNAs that are thought to
      regulate the expression of as many as one-third of all human messenger RNAs
      (mRNAs). miRNAs are thought to be involved in diverse biological processes,
      including tumorigenesis. Analysis of miRNA levels may have diagnostic
      implications. Evidence shows that numerous viruses interact with the miRNA
      machinery, and that a number of viruses encode their own miRNAs. It seems likely
      that miRNAs will be implicated in many human diseases. Manipulation of miRNA
      levels by gene therapy provides an attractive new approach for therapeutic
      development. This review focuses on approaches to manipulate miRNA levels in
      cells and in vivo, and the implications for gene therapy. Furthermore, we discuss
      the use of endogenous miRNAs as scaffolds for the expression of RNA interference
      (RNAi) as well as competition between exogenous RNAi triggers and endogenous
      miRNAs. Because short interfering RNAs can also act as miRNAs, seed matches with
      the 3' untranslated regions of genes should be avoided to prevent off-target
      effects. Last, we discuss the use of miRNAs to avoid immune responses to viral
      vectors.

PMID- 18092922
TI  - Pioneers in telemedicine. Interview.

PMID- 18092923
TI  - The relationship of a diabetes telehealth eye care program to standard eye care
      and change in diabetes health outcomes.
AB  - Several studies suggest that telehealth eye care programs that combine retinal
      imaging, education, and some care management can improve patient adherence to
      annual, comprehensive eye examinations and follow-up treatments. Little is known,
      however, about whether such programs relate to other, more distal outcomes that
      affect diabetic eye disease, such as blood glucose control. This paper assesses
      the relationship of participation in a diabetes telehealth eye care program with
      standard, face-to-face eye care as well as improvements in other diabetes-related
      health outcomes. We conducted a retrospective study using data from electronic
      medical records of Joslin Diabetes Center (n=13,752). The data span 2 years:
      baseline and follow-up. Subjects' eye care groups were no eye care, eye care
      outside of the clinic, standard eye care at the clinic, or participation in the
      Joslin Vision Network telehealth eye care program. We analyzed the relationship
      of participation in the telehealth eye care program at baseline to follow-up eye
      care groups and changes in hemoglobin A1c, low density lipoprotein levels, and
      systolic blood pressure. The results show that participation in the telehealth
      eye care program was significantly correlated with whether subjects later
      obtained standard eye care, improvement in hemoglobin A1c, and improvement in low
      density lipoprotein. Thus, telehealth eye care programs that incorporate
      evaluation, education, and care planning are related to use of recommended eye
      care and improvements in certain diabetes-related health outcomes. Such programs
      can address the many aspects of care necessary to reduce risk of vision loss due
      to diabetic retinopathy and other diabetes-related complications. Future research
      might test hypotheses suggested by sociological and psychological theories
      regarding causation between participation in a telehealth eye care program and
      other diabetes care.

PMID- 18092924
TI  - Innovative programs in telemedicine.

PMID- 18092926
TI  - The slow pace of interactive video telemedicine adoption: the perspective of
      telemedicine program administrators on physician participation.
AB  - We conducted semistructured interviews with telemedicine program administrators
      as part of a national survey of physicians and managers regarding attitudes
      toward, and knowledge of, telemedicine. Telemedicine administrators were
      interviewed regarding factors affecting physician adoption of interactive video
      (IAV) telemedicine. The seven networks with which these managers were affiliated
      represented "traditional" telemedicine programs, primarily providing specialty
      teleconsultation via IAV. These programs were located in different geographic
      regions, and included both consulting and referring sites. We include data only
      for well-established networks for which multiple administrators responded. Data
      were analyzed using standard qualitative research methods. We conclude that
      reimbursement issues are important determinants of the rate of adoption, but that
      by themselves they do not fully account for the slow diffusion of IAV
      telemedicine. Likewise, appeals to physicians as rational decision-makers are
      necessary but insufficient means of increasing the volume of telemedicine within
      a network. Telemedicine networks and administrators that have been effective in
      persuading physicians to practice telemedicine or to refer patients demonstrate
      an emphasis on aggressive recruitment of physicians who will be involved actively
      in one or the other role. Most efforts to encourage physicians to adopt
      telemedicine, however, have focused on the supply of specialists, rather than
      stimulating demand among primary care providers who have patients to refer. Habit
      was identified as an important, albeit overlooked, factor explaining physician
      adoption of telemedicine.

PMID- 18092927
TI  - Distribution of telemedicine in Japan.
AB  - This paper reports the situation of telemedicine in Japan. A comprehensive
      database search showed that a total of 1,006 telemedicine projects had been
      implemented from 1997 to 2004. Teleradiology accounted for the largest proportion
      (37%) of these projects and home-care telemedicine (home telecare) accounted for
      one third of the total number of projects. The subsequent questionnaire-based
      survey revealed that 348 projects were active in 2004, indicating a more than
      twofold increase in the number of ongoing projects from the 151 projects reported
      in 1997. In particular, the use of home telecare and telepathology has exhibited
      an approximately fourfold increase since 1997. Telemedicine was most common in
      remote areas, although approximately 30% of the projects were implemented within
      urban areas. The number of telemedicine projects peaked twice: in municipalities
      with populations ranging from 10,000 to 30,000 and in municipalities with
      populations ranging from 100,000 to 300,000. However, with regard to the
      population density, there was no characteristic distribution of implementation.
      The present data suggest that in Japan, there are various population sizes and
      densities for which telemedicine may be valuable.

PMID- 18092929
TI  - User-based motion sensing and fuzzy logic for automated fall detection in older
      adults.
AB  - More than one third of community-dwelling older adults and up to 60% of nursing
      home residents fall each year, with 10-15% of fallers sustaining a serious
      injury. Reliable automated fall detection can increase confidence in people with
      fear of falling, promote active safe living for older adults, and reduce
      complications from falls. The performance of a 2-stage fall detection algorithm
      using impact magnitudes and changes in trunk angles derived from user-based
      motion sensors was evaluated under laboratory conditions. Ten healthy
      participants were instrumented on the front and side of the trunk with 3D
      accelerometers. Participants simulated 9 fall conditions and 6 common activities
      of daily living. Fall conditions were simulated on a protective mattress. The
      experimental data set comprised 750 events (45 fall events and 30 nonfall events
      per participant) that were classified by the fall detection algorithm as either a
      fall or a nonfall using inputs from 3D accelerometers. Significant differences
      for impacts recorded, trunk angle changes (p<0.01), and detection performances
      (p<0.05) were found between fall and nonfall conditions. The proposed algorithm
      detected fall events during simulated fall conditions with a success rate of 93%
      and a false-positive rate of 29% during nonfall conditions. Despite a slightly
      superior identification performance for the accelerometer located on the front of
      the trunk, no significant differences were found between the two motion sensor
      locations. Automated detection of fall events based on user-based motion sensing
      and fuzzy logic shows promising results. Additional rules and optimization of the
      algorithm will be needed to decrease the false-positive rate.

PMID- 18092935
TI  - Embryological origins of the human individual.
AB  - The human fertilized egg is not an embryo, but, more accurately, a conceptus,
      which contains all the information required to establish both the embryo and
      extraembryonic supporting tissues. The fertilized eggs of placental mammals,
      including humans, are entirely dependent upon the female's uterine environment
      for development to birth. At least half, possibly more, fertilized eggs, or
      potential lives, do not survive to birth, the greatest loss thought to occur
      during preimplantation and implantation. Which conceptuses will be lost and which
      will progress to birth cannot be predicted. The. preimplantation conceptus
      exhibits extreme developmental lability. Importantly, twinning can occur
      throughout the preimplantation and implantation phases, and thus, a single human
      individual has not emerged from the conceptus during this time period. Once the
      primitive streak is complete during early postimplantation development, identical
      twinning no longer occurs and the individual emerges. Thus, emergence of the
      human individual is a process. No single event thus far known is more important
      than any other prior to formation of the primitive streak. Formation of the
      streak is a defining moment in the origin of the individual. All further
      organization of the fetus occurs around this midline. Thus, by 14 days in the
      human, the body plan for life is established.

PMID- 18092936
TI  - Molecular mechanisms and potential clinical significance of S-glutathionylation.
AB  - Protein S-glutathionylation, the reversible binding of glutathione to protein
      thiols (PSH), is involved in protein redox regulation, storage of glutathione,
      and protection of PSH from irreversible oxidation. S-Glutathionylated protein
      (PSSG) can result from thiol/disulfide exchange between PSH and GSSG or PSSG;
      direct interaction between partially oxidized PSH and GSH; reactions between PSH
      and S-nitrosothiols, oxidized forms of GSH, or glutathione thiyl radical. Indeed,
      thiol/disulfide exchange is an unlikely intracellular mechanism for S
      glutathionylation, because of the redox potential of most Cys residues and the
      GSSG export by most cells as a protective mechanism against oxidative stress. S
      Glutathionylation can be reversed, following restoration of a reducing GSH/GSSG
      ratio, in an enzyme-dependent or -independent manner. Currently, definite
      evidence of protein S-glutathionylation has been clearly demonstrated in few
      human diseases. In aging human lenses, protein S-glutathionylation increases;
      during cataractogenesis, some of lens proteins, including alpha- and beta
      crystallins, form both mixed disulfides and disulfide-cross-linked aggregates,
      which increase with cataract severity. The correlation of lens nuclear color and
      opalescence intensity with protein S-glutathionylation indicates that protein
      thiol mixed disulfides may play an important role in cataractogenesis and
      development of brunescence in human lenses. Recently, specific PSSG have been
      identified in the inferior parietal lobule in Alzheimer's disease. However, much
      investigation is needed to clarify the actual involvement of protein S
      glutathionylation in many human diseases.

PMID- 18092937
TI  - Regulation of proliferation of skeletal muscle precursor cells by NADPH oxidase.
AB  - Skeletal muscle precursor cells are adult stem cells located among muscle fibers.
      Proliferation, migration, and subsequent differentiation of these cells are
      critical steps in the repair of muscle injury. We document in this study the
      roles and mechanisms through which the NAPDH oxidase complex regulates muscle
      precursor cell proliferation. The NADPH oxidase subunits Nox2, Nox4, p22(phox),
      p47(phox), and p67(phox) were detected in primary human and murine skeletal
      muscle precursor cells. In human muscle precursor cells, NADPH oxidase-fusion
      proteins were localized in the cytosolic and membrane compartments of the cell,
      except for p47(phox), which was detected in the nucleus. In proliferating
      subconfluent precursor cells, both Nox2 and Nox4 contributed to O(2)(-)
      production. However, Nox4 expression was significantly attenuated in
      differentiated myotubes. Proliferation of precursor cells was significantly
      reduced by antioxidants (N-acetylcysteine and apocynin), inhibition of p22(phox)
      expression by using siRNA oligonucleotides, and reduction of Nox4 and p47(phox)
      activities with dominant-negative vectors and siRNA oligonucleotides resulted in
      attenuation of activities of the Erk1/2, PI-3 kinase/AKT and NFkappaB pathways
      and significant reduction in cyclin D1 levels. We conclude that NADPH oxidase is
      expressed in skeletal muscle precursor cells and that its activity plays an
      important role in promoting proliferation of these cells.

PMID- 18092938
TI  - Mitochondria-directed therapeutics.
AB  - Mitochondria are key regulators of cell life and death and play an important role
      in a wide range of diseases, including 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 forum discusses (a) potential new mitochondrial targets for therapeutic
      intervention, including components of the electron transport chain, the
      permeability transition, and the membrane dynamics protein mitofusin-2; (b) the
      role of mitochondria-targeted antioxidants including MitoQ and SS peptides in
      modulating reactive oxygen and chlorine species induced mitochondrial
      permeabilization and cell death; and (c) the potential use of SS peptides in
      ischemia and reperfusion tissue injury. In the future, mitochondrial drug
      targeting strategies will be expected to 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- 18092939
TI  - Analgesic resveratrol?
AB  - Resveratrol, a red wine and grape-derived phytoalexin, possesses diverse
      biochemical and physiological functions that are relevant to human health and
      disease. The emergent properties of resveratrol have forced us to rethink the
      biomedical significance of the wine culture. Novel observations point to the
      hypothesis that intracerebral resveratrol treatment diminishes the sensitivity of
      rats to pain, and that the said analgesic action of resveratrol is a central
      mechanism mediated by the inhibition of cycloxygenases I and II. This novel
      implication of resveratrol and perhaps red wine drinking warrants further
      studies.

PMID- 18092940
TI  - Expression pattern of human glutaredoxin 2 isoforms: identification and
      characterization of two testis/cancer cell-specific isoforms.
AB  - The cellular redox state is associated with major cellular processes including
      differentiation, transformation, and apoptosis. Glutaredoxin 2 (Grx2) is a
      mitochondrial oxidoreductase suggested to play a critical role in protection
      against apoptotic stimuli. An alternative Grx2 transcript variant encoding a
      nonmitochondrial protein (Grx2b) was proposed before, but no data was available
      on the expression of this isoform. We have systematically investigated the
      expression of Grx2 transcript variants in human tissues and transformed cell
      lines. The transcript variant encoding mitochondrial Grx2 (Grx2a) was found to be
      ubiquitously expressed, emphasizing the general importance of the protein for
      mitochondrial redox homeostasis. In addition, we confirmed the previously
      suggested isoform Grx2b and identified a new third isoform (Grx2c) derived from
      alternative splicing of the Grx2b-encoding transcript. In normal tissue
      expression of both Grx2b and Grx2c was restricted to testes, but additionally we
      were able to demonstrate transcripts in various cancer cell lines. Both Grx2b and
      Grx2c are enzymatically active, but only Grx2c can complex the regulatory iron
      sulfur cluster described for Grx2a. Expression of GFP fusion proteins suggested a
      cytosolic and nuclear localization of both Grx2b and Grx2c. Our findings provide
      the first evidence for functions of Grx2 outside mitochondria.

PMID- 18092941
TI  - Mitofusin 2: a mitochondria-shaping protein with signaling roles beyond fusion.
AB  - Mitochondria are central organelles in metabolism, signal transduction, and
      programmed cell death. To meet their diverse functional demands, their shape is
      strictly regulated by a growing family of proteins that impinge on fission and
      fusion of the organelle. Mitochondrial fusion depends on Mitofusin (Mfn) 1 and 2,
      two integral outer-membrane proteins. Although MFN1 seems primarily involved in
      the regulation of the docking and fusion of the organelle, mounting evidence is
      implicating MFN2 in multiple signaling pathways not restricted to the regulation
      of mitochondrial shape. Here we review data supporting a role for this
      mitochondria-shaping protein beyond fusion, in regulating mitochondrial
      metabolism, apoptosis, shape of other organelles, and even progression through
      cell cycle. In conclusion, MFN2 appears a multifunctional protein whose biologic
      function is not restricted to the regulation of mitochondrial shape.

PMID- 18092942
TI  - Water in nonpolar confinement: from nanotubes to proteins and beyond.
AB  - Water molecules confined to nonpolar pores and cavities of nanoscopic dimensions
      exhibit highly unusual properties. Water filling is strongly cooperative, with
      the possible coexistence of filled and empty states and sensitivity to small
      perturbations of the pore polarity and solvent conditions. Confined water
      molecules form tightly hydrogen-bonded wires or clusters. The weak attractions to
      the confining wall, combined with strong interactions between water molecules,
      permit exceptionally rapid water flow, exceeding expectations from macroscopic
      hydrodynamics by several orders of magnitude. The proton mobility along 1D water
      wires also substantially exceeds that in the bulk. Proteins appear to exploit
      these unusual properties of confined water in their biological function (e.g., to
      ensure rapid water flow in aquaporins or to gate proton flow in proton pumps and
      enzymes). The unusual properties of water in nonpolar confinement are also
      relevant to the design of novel nanofluidic and molecular separation devices or
      fuel cells.

PMID- 18092943
TI  - Hypertension increases middle cerebral artery resting tone in spontaneously
      hypertensive rats: role of tonic vasoactive factor availability.
AB  - The present study explores the contribution of alterations in resting tone to
      cerebral artery narrowing in SHRs (spontaneously hypertensive rats) and the role
      of hypertension development. Young pre-hypertensive and adult fully hypertensive
      SHRs and age-matched Wistar-Kyoto rat controls were used. The contribution of
      basal vasoactive factors to resting tone was studied in middle cerebral arteries
      with pressure myography. Basal NO and O(2)(-) (superoxide anion) availability
      were determined with fluorescent indicators using confocal microscopy and
      lucigenin-enhanced chemiluminescence. Basal O(2)(-) was also assessed in
      mesenteric resistance arteries. Middle cerebral arteries from adult rats, but not
      young pre-hypertensive rats, had augmented myogenic responses and resting tone
      and decreased relaxation to sodium nitroprusside compared with their normotensive
      counterparts. Cerebral arteries from adult SHRs also had an increase in tonic NO
      associated with a decrease in basal O(2)(-) availability. Basal O(2)(-) was
      instead increased in mesenteric arteries from SHRs. The present results indicate
      that large cerebral arteries from SHRs have an increase in their resting tone as
      a consequence of sustained hypertension and that this is related to a decrease in
      NO responsiveness. We suggest that this increase in resting tone and myogenic
      responses could act as a protective mechanism against the development of stroke
      in SHRs. The present study also demonstrates some unusual findings regarding the
      current understanding of the NO/O(2)(-) balance in hypertension with important
      differences between vascular beds and draws attention to the complexity of this
      balance in cardiovascular health and disease.

PMID- 18092944
TI  - Expression and function of ephrin-B1 and its cognate receptor EphB2 in human
      atherosclerosis: from an aspect of chemotaxis.
AB  - Although several cytokines and chemokines have been demonstrated to play pivotal
      roles in the pathophysiological conditions of atherosclerosis, few findings exist
      regarding the expression and function of cytokine-modulating molecules such as
      ephrin-Bs and their cognate receptors, EphBs, in human atherosclerosis.
      Therefore, in the present study, we screened novel genes modulating atherogenesis
      by cDNA array and quantitatively determined them by real-time RT (reverse
      transcription)-PCR in human carotid atherosclerotic plaques. Ephrin-B1 and EphB2,
      key regulators of embryogenesis, were significantly up-regulated in plaques
      compared with those in adjacent control tissues [ephrin-B1, 0.638+/-0.106
      compared with 0.831+/-0.152, or 130% (P<0.05); EphB2, 1.296+/-0.281 compared with
      2.233+/-0.506, or 172% (P<0.05)]. Immunohistological analysis demonstrated that
      both ephrin-B1 and EphB2 were expressed in macrophages and T-lymphocytes in
      plaques as well as in monocytes, T-lymphocytes and arterial endothelial cells
      isolated from healthy adults. Interestingly, the extracellular domains of ephrin
      B1 and EphB2, the expression of which were both enhanced in stimulated THP-1
      cells, significantly inhibited spontaneous (22.5 and 27.6% respectively; P<0.01)
      and MCP-1 (monocyte chemoattractant protein-1)-dependent (29.7 and 22.6%
      respectively; P<0.01) migration of monocytes. In conclusion, these results
      demonstrate that ephrin-B1 and EphB2 are overexpressed in atherosclerotic tissue
      and might locally regulate cell migration, possibly through modulating cytokine
      related chemotaxic activity; however, the functional role of these molecules in
      atherogenesis should be investigated further.

PMID- 18092945
TI  - SPAK and OSR1: STE20 kinases involved in the regulation of ion homoeostasis and
      volume control in mammalian cells.
AB  - Since the discovery of an interaction between membrane transport proteins and the
      mammalian STE20 (sterile 20)-like kinases SPAK (STE20/SPS1-related
      proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase-1), a
      significant body of work has been performed probing the molecular physiology of
      these two kinases. To date, the function of SPAK and OSR1 is probably the best
      known of all mammalian kinases of the STE20 family. As they regulate by direct
      phosphorylation key ion transport mechanisms involved in fluid and ion
      homoeostasis, SPAK and OSR1 constitute key end-of-pathway effectors. Their
      significance in such fundamental functions as ion homoeostasis and cell volume
      control is evidenced by the evolutionary pressure that resulted in the
      duplication of the OSR1 gene in higher vertebrates. This review examines the
      distribution of these two kinases in the animal kingdom and tissue expression
      within a single organism. It also describes the main molecular features of these
      two kinases with emphasis on the interacting domain located at their extreme C
      terminus. A large portion of the present review is devoted to the extensive
      biochemical and physiological studies that have resulted in our current
      understanding of SPAK/OSR1 function. Finally, as our understanding is a work in
      progress, we also identify unresolved questions and controversies that warrant
      further investigation.

PMID- 18092946
TI  - The histidine phosphatase superfamily: structure and function.
AB  - The histidine phosphatase superfamily is a large functionally diverse group of
      proteins. They share a conserved catalytic core centred on a histidine which
      becomes phosphorylated during the course of the reaction. Although the
      superfamily is overwhelmingly composed of phosphatases, the earliest known and
      arguably best-studied member is dPGM (cofactor-dependent phosphoglycerate
      mutase). The superfamily contains two branches sharing very limited sequence
      similarity: the first containing dPGM, fructose-2,6-bisphosphatase, PhoE, SixA,
      TIGAR [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator], Sts
      1 and many other activities, and the second, smaller, branch composed mainly of
      acid phosphatases and phytases. Human representatives of both branches are of
      considerable medical interest, and various parasites contain superfamily members
      whose inhibition might have therapeutic value. Additionally, several
      phosphatases, notably the phytases, have current or potential applications in
      agriculture. The present review aims to draw together what is known about
      structure and function in the superfamily. With the benefit of an expanding set
      of histidine phosphatase superfamily structures, a clearer picture of the
      conserved elements is obtained, along with, conversely, a view of the sometimes
      surprising variation in substrate-binding and proton donor residues across the
      superfamily. This analysis should contribute to correcting a history of over- and
      mis-annotation in the superfamily, but also suggests that structural knowledge,
      from models or experimental structures, in conjunction with experimental assays,
      will prove vital for the future description of function in the superfamily.

PMID- 18092947
TI  - The lectin-like oxidized low-density-lipoprotein receptor: a pro-inflammatory
      factor in vascular disease.
AB  - Scavenger receptors are membrane glycoproteins that bind diverse ligands
      including lipid particles, phospholipids, apoptotic cells and pathogens. LOX-1
      (lectin-like oxidized low-density lipoprotein receptor-1) is increasingly linked
      to atherosclerotic plaque formation. Transgenic mouse models for LOX-1
      overexpression or gene knockout suggests that LOX-1 contributes to
      atherosclerotic plaque formation and progression. LOX-1 activation by oxidized
      LDL (low-density lipoprotein) binding stimulates intracellular signalling, gene
      expression and production of superoxide radicals. A key question is the role of
      leucocyte LOX-1 in pro-atherogenic lipid particle trafficking, accumulation and
      signalling leading to differentiation into foam cells, necrosis and plaque
      development. LOX-1 expression is elevated within vascular lesions and a serum
      soluble LOX-1 fragment appears diagnostic of patients with acute coronary
      syndromes. LOX-1 is increasingly viewed as a vascular disease biomarker and a
      potential therapeutic target in heart attack and stroke prevention.

PMID- 18092948
TI  - Relationship between age and measures of balance, strength and gait: linear and
      non-linear analyses.
AB  - An age-related decline in balance, gait and lower-extremity muscle strength
      measures may lead to increased risk of falls and fractures. Previous studies have
      reported a possible non-linear age-related decline in these measures, but the
      choice of methodological approach has limited its interpretation. Healthy
      community-dwelling women (n=212) 21-82 years of age were evaluated for strength
      [Nicholas MMT (manual muscle tester)], gait [CSA (clinical stride analyser)],
      activity [HAP (human activity profile)] and static and dynamic balance [CBS
      (Chattecx balance system), LBT (Lord's balance test) and the ST (step test)]. A
      GAM (generalized additive model) was developed for each outcome variable to
      estimate the functional relationship, with age as a continuous variable.
      Performance was maintained until 45-55 years of age, depending on the outcome
      measure. Thereafter a decline in performance was evident with increasing age in
      all measures. Overall, a significant non-linear relationship with age was
      demonstrated for lower-extremity strength measures (MMT), velocity and double
      support duration of gait (CSA) and some clinical and laboratory balance tests
      [ST, LBT (eyes open) and the CBS]. Linear relationships were demonstrated by the
      LBT with eyes closed and activity measures. Balance, lower-extremity muscle
      strength and gait may decline non-linearly with age. Our study suggests possible
      threshold effects between age and balance, muscle strength and gait measures in
      women. Further research into these threshold effects may have implications for
      the optimal timing of exercise and other interventions to reduce the risk of
      falls and fractures.

PMID- 18092949
TI  - Endoplasmic reticulum Ca2+ measurements reveal that the cardiac ryanodine
      receptor mutations linked to cardiac arrhythmia and sudden death alter the
      threshold for store-overload-induced Ca2+ release.
AB  - A number of RyR2 (cardiac ryanodine receptor) mutations linked to ventricular
      arrhythmia and sudden death are located within the last C-terminal approximately
      500 amino acid residues, which is believed to constitute the ion-conducting pore
      and gating domain of the channel. We have previously shown that mutations located
      near the C-terminal end of the predicted TM (transmembrane) segment 10, the inner
      pore helix, can either increase or decrease the propensity for SOICR (store
      overload-induced Ca2+ release), also known as spontaneous Ca2+ release. In the
      present study, we have characterized an RyR2 mutation, V4653F, located in the
      loop between the predicted TM 6 and TM 7a, using an ER (endoplasmic reticulum)
      targeted Ca2+-indicator protein (D1ER). We directly demonstrated that SOICR
      occurs at a reduced luminal Ca2+ threshold in HEK-293 cells (human embryonic
      kidney cells) expressing the V4653F mutant as compared with cells expressing the
      RyR2 wild-type. Single-channel analyses revealed that the V4653F mutation
      increased the sensitivity of RyR2 to activation by luminal Ca2+. In contrast with
      previous reports, the V4653 mutation did not alter FKBP12.6 (FK506-binding
      protein 12.6 kDa; F506 is an immunosuppressant macrolide)-RyR2 interaction.
      Luminal Ca2+ measurements also showed that the mutations R176Q/T2504M, S2246L and
      Q4201R, located in different regions of the channel, reduced the threshold for
      SOICR, whereas the A4860G mutation, located within the inner pore helix,
      increased the SOICR threshold. We conclude that the cytosolic loop between TM 6
      and TM 7a plays an important role in determining the SOICR threshold and that the
      alteration of the threshold for SOICR is a common mechanism for RyR2-associated
      ventricular arrhythmia.

PMID- 18092950
TI  - Virus-based immunotherapy of cancer: what do we know and where are we going?
AB  - Raising an efficient and sustained immune response to a growing tumour is
      extremely challenging, as tumours not only lack the capacity to induce an
      environment optimal for induction of the relevant immune response, but also tend
      to promote the development of very efficient immunosuppressive mechanisms. This
      review aims to evaluate selected cancer vaccination approaches using virus-based
      cancer vaccines. These seem promising based on their capacity to mimic natural
      infection and hence to efficiently trigger the innate immune system and in turn a
      potent cellular immune response towards the tumours. However, even when a potent
      immune response has been induced, this is often not sufficient to eliminate the
      tumour completely before the cancer cells have had time to evolve new escape
      mechanisms as a result of the selection pressure from the initial immune response
      directed towards them. Therefore, it is very likely that it is necessary to
      combine a therapeutic tumour vaccine with immunomodulating strategies in order to
      accomplish effective tumour degradation or at least to hinder metastasis. Some of
      the immunosuppressive mechanisms worth trying to manipulate will be discussed in
      this review.

PMID- 18092951
TI  - Expression of CD44s and CD44v6 in transitional cell carcinomas of the urinary
      bladder: comparison with tumour grade, proliferative activity and p53
      immunoreactivity of tumour cells.
AB  - Alterations of CD44 glycoproteins have been shown to play an important role in
      progression of various malignancies, including urothelial cancer. We investigated
      expression patterns of CD44s and CD44v6 in transitional cell carcinoma (TCC) of
      the urinary bladder in relation to tumour grade, proliferative activity, and
      immunoreactivity for p53. The selected markers were detected
      immunohistochemically in 122 samples of TCC. We found a close relationship
      between CD44s and CD44v6 expression and tumour grade. The extension of positive
      staining for CD44s and CD44v6 towards the luminal surface was a predominant
      feature of differentiated carcinomas (grades 1 and 2), suggesting deranged
      maturation of cancer cells related to their neoplastic transformation.
      Heterogeneous expression of CD44s and CD44v6 predominated in poorly
      differentiated tumours (G3-4). However, areas of squamous differentiation within
      the high-grade tumours displayed strong immunoreactivity for both CD44s and
      CD44v6. The proliferative activity and p53 overexpression increased with the
      dedifferentiation of the tumour. The results of this study are discussed in
      relation to the significance of CD44 expression in TCC and to the explanation for
      controversial results reported in previous studies on the relationship between
      CD44 expression and the biological behaviour of urothelial cells.

PMID- 18092952
TI  - CD10 expression in tumour and stromal cells of bladder carcinoma: an association
      with bilharziasis.
AB  - CD10 is a cell surface zinc metalloprotease expressed in a variety of normal cell
      types, including lymphoid precursor cells, germinal centre B lymphocytes and some
      epithelial cells. The aim of this study was to assess the prognostic value of
      CD10 in bladder carcinoma. The expression of CD10 was immunohistochemically
      assessed in 49 cases of primary bladder carcinoma in comparison with 10 non
      neoplastic normal bladder mucosa specimens. 27 cases (55%) were tumour CD10(+)
      and tumour CD10 positivity was significantly correlated with advanced stage,
      larger tumor size, and shorter mean survival time. Extensive tumoral staining
      assessed by H score further documented the positive correlation of CD10 with
      worse prognostic factors in the whole group and its subdivisions (SCC and TCC),
      in addition to its significant association with bilharziasis in SCC. Only CD10
      tumour positivity in the whole group proved to be an independent prognostic
      factor for overall survival by multivariate analysis. No significant value of
      stromal CD10 expression in the investigated bladder carcinoma cases was found.
      This study points to the prognostic value of neoplastic CD10 expression in
      bladder carcinoma and its possible importance in facilitating tumour invasion and
      metastasis. Bilharziasis could have a role in upregulation of CD10 expression in
      SCC.

PMID- 18092953
TI  - Altered expression of CK7 and CK20 in preneoplastic and neoplastic lesions in
      ulcerative colitis.
AB  - This study is based on all patients with ulcerative colitis from a defined
      catchment area in Northern Sweden in a still ongoing colonoscopy surveillance
      programme, which started in 1977. From this material we selected tissue from
      eight groups of patients consisting of normal control biopsies (5), inactive
      colitis (10), active colitis (10), findings of low-grade dysplasia (10), high
      grade dysplasia (6), aneuploidy (without dysplasia and with subsequent dysplasia)
      (10), and ulcerative colitis-associated cancers (5). The samples were evaluated
      according to immunohistochemical expression of CK7 and CK20. Colonic mucosa from
      normal controls and inactive colitis was found to be completely negative for CK7.
      In 9 out of 10 patients with active colitis, CK7 was sparsely expressed in a
      patchy manner and connected with active epithelial inflammatory areas. 7 out of
      10 patients with low-grade dysplasia and 3 out of 6 with high-grade dysplasia
      were positive for CK7. Samples with aneuploidy without dysplasia were completely
      negative, while 2 out of 6 showing subsequent dysplasia were positive. Of the
      five cancers, two were positive for CK7. CK20 was expressed in nearly all samples
      but relatively more in the lower part of the crypts in neoplasia-associated
      lesions. Our results indicate a possible relationship between expression of CK7
      and CK20 and neoplastic development of colorectal mucosa in patients with
      ulcerative colitis. Further studies are needed to elucidate whether these
      findings have clinical significance.

PMID- 18092954
TI  - Atrial natriuretic peptide and CD34 overexpression in human idiopathic dilated
      cardiomyopathies.
AB  - Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of
      unknown cause characterized by ventricular chamber enlargement with impaired
      contractile function. In familial forms of IDCM, mutations of genes coding for
      cytoskeletal proteins related to force transmission, such as dystrophin, cardiac
      actin, desmin, and delta-sarcoglycan, have been identified. Here, we report the
      data of a retrospective investigation carried out to evaluate the expression of
      atrial natriuretic peptide (ANP), CD34, troponin T and nestin in the myocardium
      of patients affected with IDCM. Formalin-fixed and paraffin-embedded consecutive
      tissue sections from the ventricular wall of 10 human normal hearts (NH)
      following forensic autopsy and 22 IDCM (living explanted hearts) were studied
      using primary monoclonal antibodies against ANP, CD34, troponin T and nestin by
      immunohistochemistry. Myocardial fibers were counted independently by three
      pathologists. Statistics included analysis of variance, log-rank test for Kaplan
      Meier analysis, and kappa assessment for intra- and inter-observer variability.
      ANP and CD34 were significantly overexpressed in IDCM compared to NH (p<0.05).
      Conversely, troponin T and nestin expression levels did not show significant
      variation. Inter-observer kappa statistics showed a value of 0.87 and intra
      observer kappa statistics a value of 0.98. Evaluation of the marker distribution
      in the myocardium of patients with IDCM CD34 expression curve was similar to that
      of troponin T (p<0.0001), although two groups could be identified. Patients with
      a difference of more than 20 myocardial fibers in expression of CD34 and troponin
      T had a somewhat less favorable survival although the difference was not
      significant. The analysis of cells positive for troponin T resulted in a similar
      number of cardiac fibers between NH and IDCM. This is in agreement with cardiac
      enlargement present in IDCM, which is due to ventricular dilatation rather than
      increased number of myocytes. Moreover, the expression of nestin, a marker of
      activation of myocardial precursors, did not change either, and this may confirm
      that there are no hyperplastic phenomena in the IDCM pathogenesis. The increase
      in ANP-positive cells in IDCM could be a consequence of neurohormonal activation
      due to a decline in the impaired myocyte contractility. Furthermore, since it was
      already shown that ANP could be important in the control of vascular remodeling,
      we postulated that the increase in CD34-positive cells might be functionally
      correlated with the increase in ANP production. Differential expression of CD34
      and troponin T might be used in future studies to evaluate their prognostic
      value.

PMID- 18092955
TI  - Prichard's structures of the fossa ovalis are age-related phenomena composed of
      nonreplicating endothelial cells: the cardiac equivalent of cutaneous senile
      angioma.
AB  - Prichard's structures or minute endocardial deformities with lacunas of capillary
      size lined by plump endothelial cells located in the fossa ovalis are an age
      related alteration of unknown origin. In this report the histogenesis, the
      proliferative potential and the incidence in the aged of these structures are
      investigated. We have undertaken a prospective histological study of the fossa
      ovalis in a series of 111 consecutive hearts of patients aged >/=70 years
      obtained at autopsy. Included in this study was immunohistochemical staining for
      vimentin, CD31, CD34, thrombomodulin, c-kit (CD117), Ki67 (MIB1) and vascular
      endothelial growth factor receptor 2 in six cases showing these structures.
      Prichard's structures were observed in 50 hearts (45%), and were more frequent in
      males. We confirmed that these structures are age-related phenomena.
      Subendothelial structures were more common than intracavitary structures. Most
      individuals had Prichard's structures located on the right side; however, the
      structures were more numerous on the left side of the fossa ovalis. The
      immunohistochemical study revealed that Prichard's structures consisted of adult,
      fully differentiated, postmitotic-type endothelial cells. We suggest that
      Prichard's structures are formed by infolding of the endothelial lining of the
      endocardium of the fossa ovalis as an irritational response to altered blood
      flow, eddies or turbulence. A parallel can be established between Prichard's
      structures and senile angiomas as both structures increase with age; they are not
      genuine neoplasms; and they are overgrowths made up of endothelial cells with
      terminal differentiation. We propose that Prichard's structures are the cardiac
      equivalent of cutaneous senile angioma.

PMID- 18092956
TI  - Dietary sugars, serum and the biocide chlorhexidine digluconate modify the
      population and structural dynamics of mixed Candida albicans and Escherichia coli
      biofilms.
AB  - Despite the increasing recognition of the role played by mixed species biofilms
      in health and disease, the behavior and factors modulating these biofilms remain
      elusive. We therefore compared the effect of serum, two dietary sugars (sucrose
      and galactose) and a biocide, chlorhexidine digluconate, on a dual species
      biofilm (DSB) of Candida albicans and Escherichia coli and, their single species
      biofilm (SSB) counterparts. Both modes of biofilm growth on polystyrene plastic
      surfaces were quantified using a viable cell count method and visualized using
      confocal scanning laser microscopy (CSLM). Present data indicate that co-culture
      of C. albicans with varying initial concentrations of E. coli leads to a
      significant inhibition of yeast growth (r=-0.964; p<0.001). Parallel
      ultrastructural studies using CSLM and a Live/Dead stain confirmed that E. coli
      growth rendered blastospores and hyphal yeasts non-viable in DSB. SSB of C.
      albicans showed pronounced growth when its growth surface was pretreated with
      serum and by sugar supplements in the incubating medium (p<0.05). Intriguingly,
      C. albicans in DSB was more resistant to the antiseptic effect of chlorhexidine
      digluconate. Taken together, the current data elucidate some features of the
      colonization resistance offered by bacteria in mixed bacterial/fungal habitats
      and how such phenomena may contribute to the development of fungal superinfection
      during antimicrobial therapy.

PMID- 18092957
TI  - Pyrosequencing of a short hypervariable 16S rDNA fragment for the identification
      of nontuberculous mycobacteria--a comparison with conventional 16S rDNA
      sequencing and phenotyping.
AB  - Conventional methods for identification of nontuberculous mycobacteria (NTM) are
      often inexact and time consuming. Sequencing of bacterial 16S rDNA is accurate,
      rapid and effective. We have retrospectively evaluated the discriminative power
      of pyrosequencing of a short hypervariable 16S rDNA fragment as a simple and
      rapid tool for NTM characterization. A series of 312 clinical NTM isolates,
      excluding the M. avium/intracellulare complex, was investigated. When species
      could not be resolved by sequencing alone, growth rate and pigment production
      were also examined. 54% (170/312) of the isolates were unambiguously identified
      by both methods. An additional 14% (45/312) were directly identified to species
      by conventional 16S rDNA sequencing but needed complementary phenotypic analysis
      when examined by pyrosequencing. The remaining 31% (97/312) needed additional
      phenotypic analysis for both sequencing methods. We consider the pyrosequencing
      procedure to be a useful alternative for the identification of several NTM
      species, and a versatile tool for the characterization of clinical NTM isolates.
      At times it requires additional tests for definite species diagnosis and correct
      identification.

PMID- 18092958
TI  - CD34-positive interstitial cells of the human detrusor.
AB  - Interstitial cells of Cajal (ICC) are well described in the bowel wall. They are
      c-kit positive and play a role as pacemaker cells. Similar c-kit-positive cells
      have recently been described in the human bladder. The aim of this study was to
      characterize interstitial cells of the bladder detrusor using a panel of
      antibodies directed against CD117/c-kit, CD34, CD31, S100, tryptase,
      neurofilament, NSE, Factor-VIII and GFAP. A striking finding was an interstitial
      type of cell which is CD34 immunoreactive (CD34-ir) but CD117/c-kit negative. The
      cells have a tentacular morphology, enveloping and intermingling with individual
      muscle fasicles. Morphologically and immunohistochemically, they show no
      neurogenic, endothelial or mast cell differentiation. Transmission electron
      microscopy (TEM) showed the presence of interstitial cells with a round-to-oval
      nucleus, sparse perinuclear cytoplasm and long flattened processes, ramifying
      primarily in a bipolar fashion. Using immunoelectron microscopy (I-TEM) it was
      possible to view CD34 gold labelling of cells corresponding to interstitial
      cells. Although similar CD34-positive cells have been demonstrated in the bowel
      wall, they have never been described in the detrusor. The ontogeny and function
      of CD34-ir, a kit-negative cell, is unknown, but it may be involved in smooth
      muscle contraction.

PMID- 18092959
TI  - Bone marrow histomorphology and JAK2 mutation status in essential
      thrombocythemia.
AB  - A retrospective study of 38 essential thrombocythemia (ET) patients was
      conducted, reviewing bone marrow biopsies according to WHO criteria using a
      semiquantitative scoring system. Four patients did not fulfil the WHO criteria
      for a myeloproliferative disorder and one biopsy was insufficient for evaluation.
      14 patients were reclassified as having prefibrotic idiopathic myelofibrosis
      (IMF), whilst the ET diagnosis was sustained in 19 patients. The individual bone
      marrow parameters of the reviewed diagnosis showed no correlation with JAK2 V617F
      mutation status, which was determined by a highly sensitive quantitative real
      time PCR (qPCR) method. However, we could confirm previous findings of higher
      haemoglobin and lower platelet levels in the JAK2 V617F positive patients. Thus,
      the well-established phenotypic relationship of JAK2-positive ET and PV at the
      biochemical and molecular level was not recorded as regards bone marrow
      morphology according to the WHO criteria. Accordingly, the WHO concept of two
      distinct entities, ET and prefibrotic IMF, does not seem to fit the model of JAK2
      positive ET as part of a biological continuum of JAK2 V617F-positive chronic
      myeloproliferative disorders.

PMID- 18092960
TI  - Mutational and expressional analysis of BNIP3, a pro-apoptotic Bcl-2 member, in
      gastric carcinomas.
AB  - Cell death deregulation is a hallmark of human cancers. BNIP3 was initially
      identified as a pro-apoptotic member of the Bcl-2 family and plays an important
      role in apoptosis, necrosis and autophagy. The aim of this study was to see
      whether alterations of BNIP3 protein expression and somatic mutation of the BNIP3
      gene are characteristics of human cancers. We analyzed the expression of BNIP3
      protein in 60 gastric adenocarcinomas by immunohistochemistry. In addition, we
      analyzed BNIP3 mutation in the DNA sequences encoding BH3 (Bcl-2 homology3) and
      TM (transmembrane) domains that are important in the cell death function of BNIP3
      by single-strand conformation polymorphism (SSCP) in 48 colorectal, 48 gastric,
      and 48 breast carcinomas, and 48 acute leukemias. By immunohistochemistry, BNIP3
      protein was detected in 40 of the 60 carcinomas (67%). Both early and advanced
      gastric carcinomas expressed BNIP3. There was no significant association between
      BNIP3 expression and clinicopathologic characteristics, including invasion,
      metastasis and stage. In contrast to the cancer cells, epithelial cells in normal
      gastric mucosa showed no or weak expression of BNIP3. Mutational analysis
      revealed BNIP3 mutation in neither the BH3 nor the TM domain, suggesting that
      BNIP3 mutation in these domains is not a direct target of inactivation in
      gastric, colorectal and breast carcinomas, and acute leukemias. Increased
      expression of BNIP3 in the malignant gastric epithelial cells compared to the
      normal mucosal epithelial cells suggests that BNIP3 expression might play a role
      in gastric carcinoma development.

PMID- 18092961
TI  - Performance of commercial latex agglutination tests for the differentiation of
      Candida dubliniensis and Candida albicans in routine diagnostics.
AB  - Candida dubliniensis is phenotypically similar to Candida albicans and may
      therefore be underdiagnosed in the clinical microbiology laboratory. The
      performance of Bichro-Dubli latex agglutination test for rapid species
      identification of C. dubliniensis was prospectively evaluated on 111 vaginal and
      118 respiratory isolates. These had presumptively been identified as C.
      albicans/C. dubliniensis by their green colonies on CHROMagar Candida plates.
      Bichro-Dubli test identifed 2 (1.8%) vaginal and 6 (5.1%) respiratory isolates as
      C. dubliniensis. The test was also positive for 37 C. dubliniensis control
      strains characterised by 18S-28S DNA-sequencing. Bichro-Dubli test is thus a
      sensitive and accurate tool for rapid diagnostics in routine laboratories.

PMID- 18092962
TI  - Helicobacter pylori: longer survival in deep ground water and sea water than in a
      nutrient-rich environment.
AB  - Helicobacter pylori can infect the human stomach through the ingestion of water.
      Only a few studies on the morphological changes and viability of this bacteria in
      DGW (deep ground water) have been reported and none in natural seawater (SW).
      Morphological changes and the culturability of H. pylori after storage in DGW or
      SW for a week were examined to see if they could be a factor associated with the
      high infection rate in Japan. An H. pylori strain, ATCC 43504, stored in DGW and
      in SW at 4 degrees C for 7 days, was examined daily for any ultrastructural
      changes and culturability. The same H. pylori strain was also cultured in
      conventional Brucella broth culture liquid medium as control and was similarly
      observed. Bacteria kept in DGW and SW were found not only to retain their spiral
      form but also to show better culturability than those kept in the control
      nutrient-rich medium (p<0.01). Thus, natural waters were found to be more
      conducive to H. pylori survival than a nutrient-rich medium.

PMID- 18092963
TI  - Mixed testicular germ cell tumor in an adult with cryptorchidism and Down's
      syndrome.
AB  - We here present a case of mixed testicular germ cell tumor in an adult with
      cryptorchidism and Down's syndrome. A 20-year-old Japanese man with a mass in the
      left inguinal region underwent orchidectomy as a left testicular tumor was
      suspected. Histology showed a mixed germ-cell tumor with embryonal carcinoma and
      yolk sac tumor with syncytiotrophoblastic giant cells occurring in a cryptorchid
      testis. Chromosomal analysis of peripheral lymphocytes disclosed a karyotype of
      47,XY,+21[20]. Our case provides further evidence that these three conditions
      Down's syndrome, cryptorchidism and testicular germ cell tumor-may be closely
      associated. To our knowledge this is the first case of mixed germ cell tumor
      arising in a patient with Down's syndrome and cryptorchidism.

PMID- 18092964
TI  - A case of primary testicular germ cell tumor with rhabdomyosarcoma metastases as
      an example of applying the FISH method to diagnostic pathology.
AB  - We present the interesting case of a 38-year-old man with a primary malignant
      tumor of the right testis that metachronously metastasized to the urinary bladder
      and the stomach. Histologically, the testicular tumor was a mixed germ cell tumor
      composed of teratoma and embryonal carcinoma, but it also contained a sarcoma
      component of somatic type malignancy. Metastases showed rhabdomyoblastic
      differentiation histologically identical to the sarcoma component of the
      testicular tumor that was diagnosed as rhabdomyosarcoma. By applying fluorescence
      in situ hybridization (FISH) to the cytogenetic examination of cells taken from
      the periventricular lymph node metastases, we demonstrated a structural
      chromosomal aberration characteristic of testicular neoplasms, i.e. the presence
      of isochromosome 12p (i(12p)). Additionally, the diagnosis was supported by
      immunohistochemistry.

PMID- 18092965
TI  - Endometrial stromal nodule embedded into term placenta.
AB  - A 28-year-old patient presented with a 5 cm endometrial stromal tumor situated at
      the uteroplacental interface, which was diagnosed ultrasonographically at the
      28th week of pregnancy. The tumor was asymptomatic and closely attached to the
      decidua; after a normal term delivery, it was revealed to be embedded within the
      placenta. Microscopically, the neoplasm had a high mitotic rate and
      characteristic features of endometrial stromal tumor, such as CD10, progesterone
      receptor positivity, and an expansile linear, non-infiltrative pushing border.
      There were also pregnancy-related changes such as decidualization and myxoid
      change. In conclusion, the lesion was considered a benign endometrial stromal
      nodule with an unusual morphology and increased proliferation rate due to the
      hormonal stimuli of pregnancy.

PMID- 18092966
TI  - Rapid tumour-like growth of giant filiform polyposis in a patient without a
      history of chronic bowel inflammation.
AB  - Long-term inflammation of the colonic mucosa during chronic inflammatory bowel
      disease with alternating periods of ulceration and healing may lead to the
      formation of finger-like projections, so-called filiform polyps. In rare cases,
      several filiform polyps form large tumour masses, termed giant filiform
      polyposis. We present a case of giant obstructing filiform polyposis in a patient
      without previous evidence of chronic bowel inflammation. The resected ascending
      colon from a 37-year-old woman was evaluated macroscopically and microscopically,
      and the presence of gene polymorphisms was studied by means of multiplex
      capillary electrophoresis single-strand conformation polymorphism assay, DNA
      sequencing, TaqMan analysis, and restriction enzyme cleavage. The giant filiform
      polyposis was restricted to a 15 cm segment of the ascending colon, and the
      remaining colonic mucosa was entirely without inflammatory changes. During the
      post-operative follow-up period, the patient developed symptoms and signs of
      distal bowel inflammation. Gene polymorphism studies were inconclusive as to
      Crohn's disease. In conclusion, we present an unusual pathological entity of
      giant filiform polyposis, which developed relatively rapidly in a colon without
      any history or macroscopic changes suggestive of chronic inflammatory bowel
      disease. Although the patient subsequently developed symptoms in keeping with
      Crohn's disease, studies of genetic polymorphism were unable to confirm this
      notion, and colorectal tissue has not been sampled postoperatively for
      histological evaluation.

PMID- 18092968
TI  - Is there safety in numbers? The effect of cattle herding on biting risk from
      tsetse flies.
AB  - In sub-Saharan Africa, tsetse (Glossina spp.) transmit species of Trypanosoma
      which threaten 45-50 million cattle with trypanosomiasis. These livestock are
      subject to various herding practices which may affect biting rates on individual
      cattle and hence the probability of infection. In Zimbabwe, studies were made of
      the effect of herd size and composition on individual biting rates by capturing
      tsetse as they approached and departed from groups of one to 12 cattle. Flies
      were captured using a ring of electrocuting nets and bloodmeals were analysed
      using DNA markers to identify which individual cattle were bitten. Increasing the
      size of a herd from one to 12 adults increased the mean number of tsetse visiting
      the herd four-fold and the mean feeding probability from 54% to 71%; the
      increased probability with larger herds was probably a result of fewer flies per
      host, which, in turn, reduced the hosts' defensive behaviour. For adults and
      juveniles in groups of four to eight cattle, > 89% of bloodmeals were from the
      adults, even when these comprised just 13% of the herd. For groups comprising two
      oxen, four cows/heifers and two calves, a grouping that reflects the typical
      composition of communal herds in Zimbabwe, approximately 80% of bloodmeals were
      from the oxen. Simple models of entomological inoculation rates suggest that
      cattle herding practices may reduce individual trypanosomiasis risk by up to 90%.
      These results have several epidemiological and practical implications. First, the
      gregarious nature of hosts needs to be considered in estimating entomological
      inoculation rates. Secondly, heterogeneities in biting rates on different cattle
      may help to explain why disease prevalence is frequently lower in younger/smaller
      cattle. Thirdly, the cost and effectiveness of tsetse control using insecticide
      treated cattle may be improved by treating older/larger hosts within a herd. In
      general, the patterns observed with tsetse appear to apply to other genera of
      cattle-feeding Diptera (Stomoxys, Anopheles, Tabanidae) and thus may be important
      for the development of strategies for controlling other diseases affecting
      livestock.

PMID- 18092969
TI  - Endectocide residues affect insect attraction to dung from treated cattle:
      implications for toxicity tests.
AB  - A 3-year study was performed in southern Alberta, Canada to assess the effect of
      endectocide residues on the attractiveness of cattle dung to colonizing insects.
      In 2003 and 2004, insect captures were compared between pitfall traps baited with
      dung of untreated cattle and paired traps baited with dung of cattle that had
      been treated 7 days previously with topically applied doramectin, eprinomectin,
      ivermectin or moxidectin. Faecal residues associated with each compound affected
      insect captures in both spring and autumn of each year. Effects were detected (P
      < 0.05) for a total of 94 cases representing 27 insect taxa from 13 families in
      three orders (Coleoptera, Diptera, Hymenoptera). Two-fold differences in captures
      were common. Up to six-fold differences were observed. Eleven cases of attraction
      and 11 cases of repellency were associated with residues of doramectin.
      Eprinomectin tended to repel insects, with decreased captures for 19 of 29 cases
      of effect. Ivermectin showed a strong attractive effect, with increased captures
      for 17 of 25 cases. Moxidectin also showed a strong attractive effect, with
      increased captures for 17 of 18 cases. Comparisons between compounds suggested
      that results for doramectin best predicted results for eprinomectin and vice
      versa. In 2005, insect captures were compared between pitfall traps baited with
      dung of untreated cattle and traps baited with dung from cattle treated 3, 7 or
      14 days previously with topically applied doramectin. Effects were detected in 14
      cases plus one case of near significance (P= 0.053). Significant differences
      between control vs. days 3, 7 and/or 14 dung were detected in nine cases.
      Residues enhanced captures in seven of these cases. Day 14 dung affected captures
      in six of these cases. This study shows that endectocide residues can affect the
      number of insects attracted to colonize and oviposit in dung. Hence, the
      emergence of their offspring from field-colonized dung of untreated vs.
      endectocide-treated cattle should not be used as a measure of residue toxicity
      per se, but rather as a measure of 'insect activity'. Insect activity is a
      composite measure of residue toxicity, the number and species composition of
      insect colonists, and the mortality factors (e.g. predation, parasitism,
      competition) associated with the co-occurrence of these species in the dung pat.

PMID- 18092970
TI  - Evaluation of the enantiomers of 1-octen-3-ol and 1-octyn-3-ol as attractants for
      mosquitoes associated with a freshwater swamp in Florida, U.S.A.
AB  - Field studies were conducted at wooded wetlands in Gainesville, FL, U.S.A., to
      assess responses of natural populations of adult mosquitoes (Diptera: Culicidae)
      to American Biophysics MM-X and Coleman MD-2500 traps baited with enantiomers of
      1-octen-3-ol, a naturally occurring compound, and 1-octyn-3-ol, a closely related
      synthetic compound. Overall, the same species of mosquitoes were attracted by all
      enantiomers, although the (R)-(+) isomer of octenol generally attracted more
      species, and it is the isomer produced in greatest proportion in nature. Traps
      baited with the R-enantiomer caught greater numbers of mosquitoes than those
      baited with the S-enantiomer of each compound, whereas traps baited with S
      enantiomers were equally or slightly less attractive than those baited with
      carbon dioxide only.

PMID- 18092971
TI  - Courtship behaviour in the sandfly Lutzomyia longipalpis, the New World vector of
      visceral leishmaniasis.
AB  - Courtship behaviour in Lutzomyia longipalpis Lutz and Neiva (Diptera:
      Psychodidae) was examined to determine the sequence of behaviours that occur
      prior to copulation. Courtship consisted of a series of male and female touching
      and wing-flapping behaviours, with males performing a greater variety of wing
      flapping behaviours than previously described. Occurrence of male approach
      flapping, semi-circling and female stationary-flapping were all predictors of
      eventual copulation, and may coincide with the dispersal of pheromones or the
      production of auditory signals important to courtship. Touching occurred in the
      majority of observations, with contact most often made with the tips of the legs
      and antennae. This behaviour, not previously described in sandflies, was
      initiated by males and females, and may indicate the use of contact pheromones, a
      form of communication previously overlooked in L. longipalpis. Future studies are
      required to separate the auditory and chemical signals associated with wing
      flapping, and to confirm whether L. longipalpis possesses cuticular hydrocarbons
      capable of inducing behavioural responses. The identification of signals that
      inhibit sexual behaviour during courtship may be particularly relevant to
      developing mating disruption techniques against L. longipalpis.

PMID- 18092972
TI  - Abundance, biting behaviour and parous rate of anopheline mosquito species in
      relation to malaria incidence in gold-mining areas of southern Venezuela.
AB  - A longitudinal entomological and epidemiological study was conducted in five
      localities of southern Venezuela between January 1999 and April 2000 to determine
      the abundance, biting behaviour and parity of anopheline mosquitoes (Diptera:
      Culicidae) in relation to climate variables and malaria incidence. A total of
      3685 female anopheline mosquitoes, representing six species, were collected. The
      most abundant species were Anopheles marajoara Galvao & Damasceno (60.7%) and
      Anopheles darlingi Root (35.1%), which together represented 95.8% of the total
      anophelines collected. Abundance and species distribution varied by locality.
      Malaria prevalence varied from 12.5 to 21.4 cases per 1000 population.
      Transmission occurred throughout the year; the annual parasite index (API) for
      the study period was 813.0 cases per 1000 population, with a range of 71.6-2492
      per 1000 population, depending on locality. Plasmodium vivax (Grassi & Feletti)
      (Coccidia: Plasmodiidae) accounted for 78.6% of cases, Plasmodium falciparum
      (Welch) for 21.4% and mixed infections (Pv+Pf) for < 0.1%. Anopheles marajoara
      and An. darlingi were more abundant during the rainy season (April-September).
      There was no significant correlation (P > 0.05) between mosquito abundance and
      rainfall. Correlations between malaria incidence by parasite species and mosquito
      abundance were not significant (P > 0.05). Monthly parous rates were similar for
      An. marajoara and An. darlingi throughout the year, with two peaks that coincided
      with the dry-rainy transition period and the period of less rain. Peaks in the
      incidence of malaria cases were observed 1 month after major peaks in biting
      rates of parous anophelines. Anopheles darlingi engages in biting activity
      throughout the night, with two minor peaks at 23.00-00.00 hours and 03.00-04.00
      hours. Anopheles marajoara has a different pattern, with a biting peak at 19.00
      21.00 hours and 76.6% of biting occurring before midnight. Although both vectors
      bite indoors and outdoors, they showed a highly significant (P < 0.01) degree of
      exophagic behaviour. The present study constitutes the first effort to
      characterize the bionomics of anophelines in malaria endemic foci in different
      ecological situations in relation to malaria transmission in southern Venezuela
      and to provide relevant information to be considered when planning and
      implementing vector control programmes.

PMID- 18092973
TI  - Population dynamics of pest mosquitoes and potential malaria and West Nile virus
      vectors in relation to climatic factors and human activities in the Camargue,
      France.
AB  - The Camargue is an extensive wetland in the southeast of France, which is highly
      influenced by human activities. Large ponds, marshes and irrigated fields provide
      abundant potential breeding sites for mosquitoes. mosquitoes, which are important
      in terms of the nuisance they cause to people and animals, the limitations they
      impose on tourism and their potential threat to human health. Several of the
      mosquito species present are potential vectors of malaria and West Nile virus.
      Therefore, the population dynamics of these species were monitored over an entire
      breeding season during March-October 2005. Mosquito populations were sampled in
      two study areas once every 2 weeks, using CDC light traps baited with CO(2).
      Sixteen species were collected. The majority (98.7%) of the catch were Aedes
      caspius (Pallas) (Diptera: Culicidae), Culex modestus (Ficalbi), Culex pipiens L.
      and Anopheles hyrcanus (Pallas). The population dynamics of these species varied
      considerably in relation to the species' biology, climatic conditions (rainfall,
      temperature and season), water management, implementation of mosquito control
      campaigns and landscape use.

PMID- 18092974
TI  - Evidence for late Pleistocene population expansion of the malarial mosquitoes,
      Anopheles arabiensis and Anopheles gambiae in Nigeria.
AB  - Anopheles gambiae Giles s.s. and Anopheles arabiensis Patton (Diptera: Culicidae)
      are major vectors of malaria in Nigeria. We used 1115 bp of the mitochondrial COI
      gene to assess their population genetic structures based on samples from across
      Nigeria (n = 199). The mtDNA neighbour-joining tree, based on F(ST) estimates,
      separated An. gambiae M and S forms, except that samples of An. gambiae M from
      Calabar clustered with all the An. gambiae S form. Anopheles arabiensis and An.
      gambiae could be combined into a single star-shaped, parsimonious haplotype
      network, and shared three haplotypes. Haplotype diversity values were high in An.
      arabiensis and An. gambiae S, and intermediate in An. gambiae M; all nucleotide
      diversities were relatively low. Taken together, patterns of haplotype diversity,
      the star-like genealogy of haplotypes, five of seven significant neutrality
      tests, and the violation of the isolation-by-distance model indicate population
      expansion in An. arabiensis and An. gambiae S, but the signal was weak in An.
      gambiae M. Selection is supported as an important factor shaping genetic
      structure in An. gambiae in Nigeria. There were two geographical subdivisions in
      An. arabiensis: one included all southern localities and all but two central
      localities; the other included all northern and two central localities. Re
      analysing an earlier microsatellite dataset of An. arabiensis using a Bayesian
      method determined that there were two distinctive clusters, northern and
      southern, that were fairly congruent with the mtDNA subdivisions. There was a
      trend towards decreasing genetic diversity in An. arabiensis from the northern
      savannah to the southern rainforest that corroborated previous data from
      microsatellites and polytene chromosomes.

PMID- 18092975
TI  - Investigations of dengue-2 susceptibility and body size among Aedes aegypti
      populations.
AB  - The mosquito Aedes aegypti (L.) (Diptera: Culicidae) is the primary global vector
      for dengue virus (DENV), yet considerable genetic variation exists among
      populations in terms of its competence to vector DENV. Variability in adult body
      size has also been observed among various mosquito populations and several
      studies have reported a relationship between body size and arbovirus
      dissemination, although most of these relied on artificially derived variation in
      body size. Here we examine the relationship between body size and disseminated
      DENV infection among 10 Ae. aegypti populations reared under optimum laboratory
      conditions. Body size variability was inferred from wing length measurements and
      DENV competence was evaluated as the proportion of individuals with disseminated
      infections following exposure to the dengue-2 JAM1409 strain. There were
      significant differences in mean wing lengths among populations (anova, F(9,22)=
      7.10, P < 0.0001), ranging from 2.16 mm (Bangkok population) to 2.79 mm (MOYO-S
      [susceptible] population). We also observed significant differences among some
      populations in mean DENV infection rates (Waller-Duncan K-ratio t-test), ranging
      from 19.54% (MOYO-R [refractory] population) to 56.60% (MOYO-S population).
      However, we did not observe evidence for significant interactions between body
      size and DENV dissemination. We suggest that either the two traits are
      genetically independent or that our ability to detect interactions between them
      was limited by their respective inheritances as quantitative traits.

PMID- 18092976
TI  - Virus recovery rates for wild-type and live-attenuated vaccine strains of African
      horse sickness virus serotype 7 in orally infected South African Culicoides
      species.
AB  - Previously reported virus recovery rates from Culicoides (Avaritia) imicola
      Kieffer and Culicoides (Avaritia) bolitinos Meiswinkel (Diptera, Ceratopogonidae)
      orally infected with vaccine strain of African horse sickness virus serotype 7
      (AHSV-7) were compared with results obtained from concurrently conducted oral
      infections with five recent AHSV-7 isolates from naturally infected horses from
      various localities in South Africa. Culicoides were fed sheep bloods spiked with
      10(7.6) TCID(50)/mL of a live-attenuated vaccine strain AHSV-7, and with five
      field isolates in which virus titre in the bloodmeals ranged from 10(7.1) to
      10(8.2) TCID(50)/mL). After an extrinsic incubation of 10 days at 23.5 degrees C,
      virus recovery rates were significantly higher in C. imicola (13.3%) and C.
      bolitinos (4.2%) infected with the live-attenuated virus than in midges infected
      with any of the field isolates. The virus recovery rates for the latter groups
      ranged from 0% to 9.5% for C. imicola and from 0% to 1.5% for C. bolitinos. The
      C. imicola population at Onderstepoort was significantly more susceptible to
      infection with AHSV-7 isolated at Onderstepoort than to the virus strains
      isolated from other localities. Results of this study suggest that tissue culture
      attenuation of AHSV-7 does not reduce its ability to orally infect competent
      Culicoides species and may even lead to enhanced replication in the vector.
      Furthermore, oral susceptibility in a midge population appears to vary for
      geographically distinct isolates of AHSV-7.

PMID- 18092977
TI  - Effects of horsefly (Tabanidae) salivary gland extracts on isolated perfused rat
      heart.
AB  - The speed with which horseflies (Diptera: Tabanidae) obtain a bloodmeal suggests
      they have potent vasodilators. We used isolated perfused rat heart to examine the
      vasoactivity of salivary gland extracts (SGEs) of three horsefly species,
      Hybomitra bimaculata Macquart, Tabanus bromius Linnaeus and Tabanus glaucopis
      Meigen. Administration of horsefly SGEs to the heart produced biphasic coronary
      responses: a decrease and subsequent increase in coronary flow (CF),
      characterized by initial vasoconstriction followed by prolonged vasodilation of
      coronary vessels. However, although SGEs of H. bimaculata induced a significant
      decrease in left ventricular pressure (LVP), the effect on changes in CF was not
      significant except at the highest dose tested. The ability to reduce LVP without
      significantly lowering CF, or affecting heart rate and rhythm, represents a
      unique set of properties that have considerable therapeutic potential if they can
      be reproduced by a single molecule.

PMID- 18092978
TI  - 'No one agrees except for those of us who have it': endometriosis patients as an
      epistemological community.
AB  - This paper contributes to the literature on patients' claims-making work by
      analysing the epistemological strategies and standards used by members of an
      endometriosis patient community. It draws upon focus group research with members
      of a support group for endometriosis sufferers, and an open-ended survey of an e
      mail list for women with the disease. Lynn Hankinson Nelson's (1993) concept of
      epistemological community is used to examine standards and practices for
      developing and evaluating knowledge used by women with endometriosis. Particular
      attention is paid to the use and centrality of the notion of experience within
      this community.

PMID- 18092979
TI  - Explaining non-help-seeking amongst young adults with mental distress: a dynamic
      interpretive model of illness behaviour.
AB  - Mental disorder is common amongst young adults and is associated with many
      adverse outcomes. Data, however, indicate that young adults are particularly
      unlikely to seek help for such distress. This paper describes a qualitative study
      of 23 young adults (aged 16 to 24 years) with mental distress. Interviewing was
      used to obtain detailed narratives of illness behaviour and to explore reasons
      for non-help-seeking. Help-seekers and non-help-seekers were interviewed. The
      findings allowed development of an explanatory model - the cycle of avoidance
      (COA) - which contributes towards attempts to provide a dynamic understanding of
      help-seeking behaviour. Dominant approaches tend to be deterministic and static
      and to account for non-help-seeking in terms of 'barriers' to care, which
      although easily translated into targets for policy intervention, are superficial
      representations of complex issues. The COA conceptualises help-seeking as a
      circular process and offers a model of 'non-help-seeking' in which lay
      conceptions of mental distress, the social meanings attached to 'help-seeking'
      and treatment, and the purposeful action of individuals, assume central
      importance. Although derived in the context of young adulthood and mental
      distress, this model may have wider applicability as a theoretical template for
      explaining non-help-seeking in other age groups and conditions, and other illness
      behaviours.

PMID- 18092980
TI  - The loss of possibility: scientisation of death and the special case of early
      miscarriage.
AB  - This paper explores the special nature of bereavement in the case of first
      trimester miscarriage. It is theoretically informed by the sociological
      literature concerning death and bereavement and is empirically grounded in
      interviews with 79 women. We argue that the 'scientisation of death' in modern
      societies contributes to the uncertainty and isolation which distinguish early
      miscarriage as a unique form of loss. In the absence of clear cultural scripts to
      draw upon, many women interviewed gave meaning to their loss as 'what might have
      been' or what we call 'the loss of possibility'. Some women juxtaposed the
      failure of their pregnancy with that of modern medicine either to prevent the
      loss or provide a credible explanation for their miscarriage. Little research has
      been conducted in this area, since the pioneering work of Lovell (1983) and Cecil
      (1984). Our research draws on one of the largest and most systematic bodies of
      data ever collected on early miscarriage, and provides continued evidence of the
      traumas of miscarriage. The strategies employed by women to make sense of, and
      come to terms with, their experience of miscarriage are explored, employing a
      typology of pre-modern, modern and postmodern responses.

PMID- 18092981
TI  - Consent and nothing but consent? The organ retention scandal.
AB  - The organ retention scandal arose in the UK in the autumn of 1999 when knowledge
      of the practice of organ and tissue retention after post-mortem for subsequent
      diagnostic, teaching, audit and research purposes fully entered the public
      domain. Many families were shocked and distressed to realise that by allowing a
      post-mortem on their relative or child they were also deemed to have agreed to
      the long-term retention of organs and tissues and thus had buried or cremated, as
      they perceived it, not a 'whole' body but an 'empty shell'. Subsequently,
      informed consent was placed at the centre of recommendations for reform, now
      given expression in the Human Tissue Act (2004). Through a discourse analysis of
      the documentary evidence produced in the wake of the organ retention scandal, I
      argue that the emphasis on informed consent masks concerns about body wholeness.
      In addition, whilst informed consent is posited as key in 'balancing' the rights
      of the individual over the needs of medical science, this position is tempered by
      the concurrent presence of notions of the gift relationship and post-mortem
      citizenship. Incorporating these notions alongside the discourse of consent also
      renders concerns about the commodification of the body less acute.

PMID- 18092982
TI  - Internet social support groups as moral agents: the ethical dynamics of HIV+
      status disclosure.
AB  - This paper examines how, on Internet HIV/AIDS support groups, participants
      discuss the ethics of disclosing HIV seropositivity to partners. The data consist
      of all mentions of disclosure culled from over 16,000 pages overall of posts from
      16 different groups, hosted on seven separate sites. The paper focuses on two
      main questions. First, apart from providing support and information, did the
      groups also debate moral dilemmas (and, despite groups' common perception as
      'safe spaces' for non-judgmental exchanges, did these discussions include moral
      judgments and conflicts)? Secondly, did use of this new medium generate a new,
      alternative ethical discourse, or merely replicate existing discourses? The data
      demonstrate that online support groups did engage in debating, and trying
      verbally to enforce, certain views of the ethics of seropositivity disclosure.
      The most common view advocated full disclosure, though a range of positions
      existed. Unlike with most online support groups described elsewhere, these
      discussions often included harshly-expressed moral judgments. The groups did not
      generate a truly new, alternative discourse, but served as clearinghouses for and
      transmitters of existing 'off-line' discourses, both mainstream and alternative.
      Implications and limitations of the present study, and areas for further
      research, are discussed.

PMID- 18092983
TI  - 'It puts things out of your control': fear of consequences as a barrier to
      patient disclosure of mental health issues to general practitioners.
AB  - Research indicates that there is a high level of trust in health professionals
      but also a high level of non-disclosure of mental health issues to general
      practitioners (GPs). This paper explores the issue of patients' willingness to
      disclose mental health problems to GPs through interviews with 33 patients from
      the lower half of the North Island of New Zealand. Patients' willingness to
      disclose related to a range of factors but this paper focuses on fear and sense
      of control as these issues have received little attention in the extant
      literature and provide important discussion points for the conduct of
      consultations. Fear of the consequences of consultation warrants attention if
      general practice is to be promoted as the preferred point of contact for mental
      health consultations. The research reported here suggests that trust in a range
      of institutions and agencies, not just in the individual practitioner, would need
      to be achieved for the GP to be the preferred point of contact.

PMID- 18092984
TI  - Health, morality, and infant feeding: British mothers' experiences of formula
      milk use in the early weeks.
AB  - The way mothers feed their babies is, internationally, the subject of research,
      health policy initiatives, and popular discussion, which commonly affirm the
      mantra 'breast is best'. On one level, this mantra reflects scientific evidence
      about nutrition and maternal and infant health. From a socio-cultural
      perspective, the pro-breastfeeding message has, however, been considered an
      aspect of morality, which influences maternal identity in important ways. This
      article explores this idea. It does so primarily by reporting and discussing some
      findings from a study about British mothers' experiences of using formula milk
      for infant feeding. The paper begins by contextualising this discussion by
      briefly outlining some aspects of the construction of infant feeding as a social
      problem in Britain, focusing in particular on the influence of 'the new paradigm
      of health'.

PMID- 18092985
TI  - Choosing embryos: ethical complexity and relational autonomy in staff accounts of
      PGD.
AB  - The technique of preimplantation genetic diagnosis (PGD) is commonly explained as
      a way of checking the genes of embryos produced by IVF for serious genetic
      diseases. However, complex accounts of this technique emerged during ethics
      discussion groups held for PGD staff. These form part of a study exploring the
      social processes, meanings and institutions that frame and produce 'ethical
      problems' for practitioners, scientists and others working in the specialty of
      PGD in the UK. Two 'grey areas' raised by staff are discussed in terms of how far
      staff are, or in the future may be, able to support autonomous choices of
      women/couples: accepting 'carrier' embryos within the goal of creating a
      'healthy' child; and sex selection of embryos for social reasons. These grey
      areas challenged the staff's resolve to offer individual informed choice, in the
      face of their awareness of possible collective social effects that might ensue
      from individual choices. We therefore argue that these new forms of choice pose a
      challenge to conventional models of individual autonomy used in UK genetic and
      reproductive counselling, and that 'relational autonomy' may be a more suitable
      ethical model to describe the ethical principles being drawn on by staff working
      in this area.

PMID- 18092990
TI  - Ever deeper phylogeographies: trees retain the genetic imprint of Tertiary plate
      tectonics.
AB  - Changes in species distributions after the last glacial maximum (c. 18 000 years
      bp) are beginning to be understood, but information diminishes quickly as one
      moves further back in time. In this issue of Molecular Ecology, Magri et al.
      (2007) present the fascinating case of a Mediterranean tree species whose
      populations preserve the genetic imprints of plate tectonic events that took
      place between 25 million years and 15 million years ago. The study provides a
      unique insight into the pace of evolution of trees, which, despite interspecific
      gene flow, can retain a cohesive species identity over timescales long enough to
      allow the diversification of entire plant and animal genera.

PMID- 18092991
TI  - Male parentage in dependent-lineage populations of the harvester ant Pogonomyrmex
      barbatus.
AB  - We investigated the extent to which workers reproduce in a dependent-lineage
      population of the monogynous harvester ant Pogonomyrmex barbatus. Dependent
      lineage populations contain two interbreeding, yet genetically distinct
      mitochondrial lineages, each associated with specific alleles at nuclear loci.
      Workers develop from matings between lineages, and queens develop from matings
      within lineages, so queens must mate with males of both lineages to produce
      daughter queens and workers. Males develop from unfertilized eggs and are
      haploid. Worker production of males could lead to male-mediated gene flow between
      the lineages if worker-produced males were reproductively capable. This could
      result in the loss of the dependent-lineage system, because its persistence
      depends on the maintenance of allelic differences between the lineages. To
      investigate the extent of worker reproduction in P. barbatus, we genotyped 19-20
      males and workers from seven colonies, at seven microsatellite loci, and 1239
      additional males at two microsatellite loci. Our methods were powerful enough to
      detect worker reproduction if workers produced more than 0.39% of males in the
      population. We detected no worker-produced males; all males appeared to be
      produced by queens. Thus, worker reproduction is sufficiently infrequent to have
      little impact on the dependent-lineage system. These results are consistent with
      predictions based on inclusive fitness theory because the effective queen mating
      frequency calculated from worker genotypes was 4.26, which is sufficiently high
      for workers to police those that attempt to reproduce.

PMID- 18092992
TI  - Population genetic structure of Earth's largest fish, the whale shark (Rhincodon
      typus).
AB  - Large pelagic vertebrates pose special conservation challenges because their
      movements generally exceed the boundaries of any single jurisdiction. To assess
      the population structure of whale sharks (Rhincodon typus), we sequenced complete
      mitochondrial DNA control regions from individuals collected across a global
      distribution. We observed 51 single site polymorphisms and 8 regions with indels
      comprising 44 haplotypes in 70 individuals, with high haplotype (h = 0.974 +/-
      0.008) and nucleotide diversity (pi = 0.011 +/- 0.006). The control region has
      the largest length variation yet reported for an elasmobranch (1143-1332 bp).
      Phylogenetic analyses reveal no geographical clustering of lineages and the most
      common haplotype was distributed globally. The absence of population structure
      across the Indian and Pacific basins indicates that oceanic expanses and land
      barriers in Southeast Asia are not impediments to whale shark dispersal. We did,
      however, find significant haplotype frequency differences (AMOVA, Phi(ST) =
      0.107, P < 0.001) principally between the Atlantic and Indo-Pacific populations.
      In contrast to other recent surveys of globally distributed sharks, we find much
      less population subdivision and no evidence for cryptic evolutionary partitions.
      Discovery of the mating and pupping areas of whale sharks is key to further
      population genetic studies. The global pattern of shared haplotypes in whale
      sharks provides a compelling argument for development of broad international
      approaches for management and conservation of Earth's largest fish.

PMID- 18092993
TI  - Selective sweeps in the homoploid hybrid species Helianthus deserticola:
      evolution in concert across populations and across origins.
AB  - The evolution of different populations within a species in response to selective
      pressures can potentially happen in three different ways. It can occur in
      parallel, where similar changes occur independently in each population in
      response to selection; in concert, where the spread of an adaptive mutation
      across a species' range results in a single allele fixing in each population; or
      populations can diverge in response to local selective pressures. We explored
      these possibilities in populations of the homoploid hybrid species Helianthus
      deserticola relative to its parental species Helianthus annuus and Helianthus
      petiolaris using an analysis of variation in 96 expressed sequence tag-based
      microsatellites. A total of nine loci showed evidence consistent with recent
      selection at either the species or population level, although two of these genes
      were discarded because the apparent sweep did not occur relative to the parent
      from which the locus was derived. Between one and five loci showed a putative
      sweep across the entire species range with the same microsatellite allele fixed
      in each population. This pattern is consistent with evolution in concert despite
      geographical isolation and potential independent origins of the populations. Only
      one population of H. deserticola showed candidate sweeps that were unique
      compared to the rest of the species, and this population has also potentially
      experienced recent admixture with the parental species.

PMID- 18092994
TI  - Mating system variation and morph fluctuations in a polymorphic lizard.
AB  - In polymorphic male painted dragon lizards (Ctenophorus pictus), red males win
      staged contests for females over yellow males, and yellow males have greater
      success in staged sperm competition trials than red males. This predicts
      different reproductive strategies in the wild with red males being more coercive
      or better mate guarders than yellow males. Yellow males would be expected to sire
      more offspring per copulation and have a greater proportion of offspring from
      clutches with mixed paternity. However, here we show using microsatellites that
      the frequency of mixed paternity in the wild is low (< 20% on average across
      years), that all morphs on average have the same number of offspring sired per
      year, and that mating system variation (polyandry vs. monandry) is strongly
      correlated with perch density on male territories. Furthermore, a logistic
      regression on male successful vs. unsuccessful mate acquisition showed that red
      males were under negative selection when they dominated the population, which
      suggests ongoing frequency dependent selection on male colouration.

PMID- 18092995
TI  - Trypanosoma brucei brucei induces alteration in the head proteome of the tsetse
      fly vector Glossina palpalis gambiensis.
AB  - Parasitic manipulations of host behaviour are known from a wide range of host
      parasite associations. However, the understanding of these phenomena is far from
      complete and detailed investigation of their proximate causes is needed. Many
      studies report behavioural modifications, such as altered feeding rates in tsetse
      fly (Glossina) infected with the mature transmissible stage (i.e. metacyclic) of
      the trypanosomes. Here, bidimensional (2D) gel electrophoresis and mass
      spectrometry were employed to analyse and compare the head proteome between four
      Glossina palpalis gambiensis categories (uninfected, refractory, mature
      infection, immature infection). Twenty-four protein spots specifically present or
      absent in the head of metacyclic-infected flies were observed. These protein
      spots were subsequently identified and functionally classified as glycolitic,
      neurotransmiter synthesis, signalling, molecular chaperone and transcriptional
      regulation proteins. Our results indicate altered energy metabolism in the head
      of metacyclic-infected tsetse flies. Some of the proteins identified, such as
      casein kinase 2 and jun kinase have previously been shown to play critical roles
      in apoptosis in insect neurones. In addition, we found two pyridoxal-dependent
      decarboxylases (dopa decarboxylase and alpha methyldopa hypersensitive protein),
      suggesting a modification of serotonin and/or dopamine in the brain of metacyclic
      infected tsetse flies. Our data pave the way for future investigation of the
      alteration of the glossina central nervous system during infection by
      trypanosomes.

PMID- 18092997
TI  - Expressed sequence tags from the midgut of Epiphyas postvittana (Walker)
      (Lepidoptera: Tortricidae).
AB  - The midgut is a key tissue in insect science. Physiological roles include
      digestion and peritrophic membrane function, as well as being an important target
      for insecticides. We used an expressed sequence tag (EST) approach to identify
      candidate genes and gene families involved in these processes in the light brown
      apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae). Two cDNA
      libraries were constructed from dissected midgut of third to fifth instar larvae.
      Clustering analysis of 6416 expressed sequence tags produced 1178 tentative
      unique genes comprising 725 tentative contigs and 453 singletons. The sequences
      show similar codon usage to sequences from other lepidopterans, a Kozak consensus
      sequence similar to Drosophila and single nucleotide polymorphisms (SNPs) were
      detected at a frequency of 1.35/kb. The identity of the most common Interpro
      families correlates well with major known functions of the midgut. Phylogenetic
      analysis was conducted on representative sequences from selected multigene
      families. Gene families include a broad range of digestive proteases, lipases and
      carbohydrases that appear to have degradative capacity against the major food
      components found in leaves, the diet of these larvae; and carboxylesterases,
      glutathione-S-transferases and cytochrome P450 monooxygenases, potentially
      involved in xenobiotic degradation. Two of the larger multigene families, serine
      proteases and lipases, expressed a high proportion of genes that are likely to be
      catalytically inactive.

PMID- 18092998
TI  - The nicotinic acetylcholine receptor subunits Mdalpha5 and Mdbeta3 on autosome 1
      of Musca domestica are not involved in spinosad resistance.
AB  - Spinosad is a relatively new insecticide that exerts its toxic action via
      nicotinic acetylcholine receptors (nAChRs). Spinosad resistance in house flies
      appears to be due to an altered target site. To evaluate the molecular basis of
      spinosad resistance, two nAChR subunit genes, Mdalpha5 and Mdbeta3 were cloned
      and characterized from an insecticide-susceptible (aabys) and spinosad resistant
      (rspin) strain of the house fly, Musca domestica. The Mdalpha5 and Mdbeta3 cDNAs
      encode proteins of 781 and 432 amino acid residues, respectively. Phylogenetic
      analysis with insect nAChR subunits suggested that Mdalpha5 and Mdbeta3 are most
      closely related to Dalpha5 and Dbeta3 of Drosophila melanogaster, respectively.
      Mdbeta3 is intronless, which is unique among all previously described nAChR
      genes. A-to-I RNA editing was found at 13 sites in Mdalpha5, eleven of which
      resulted in amino acid substitutions. No evidence for A-to-I RNA editing was
      found in Mdbeta3. Mdalpha5 expression, quantified by real time PCR, was 340- and
      23-fold higher in the head and thorax than in the abdomen. Mdbeta3 expression was
      more uniform, being only 2.4-fold higher in the head and 1.4-fold lower in the
      thorax, compared to the abdomen. There was no difference in the expression of
      Mdalpha5 and Mdbeta3 between the aabys and rspin strains. Although Mdalpha5 and
      Mdbeta3 both map to the same chromosome as spinosad resistance, there were no
      unique features of either gene in rspin, relative to the aabys strain. This
      suggests neither Mdalpha5 nor Mdbeta3 is responsible for spinosad resistance in
      house flies.

PMID- 18092996
TI  - Hepatopancreatic multi-transcript expression patterns in the crayfish Cherax
      quadricarinatus during the moult cycle.
AB  - Alterations of hepatopancreatic multi-transcript expression patterns, related to
      induced moult cycle, were identified in male Cherax quadricarinatus through cDNA
      microarray hybridizations of hepatopancreatic transcript populations. Moult was
      induced by X-organ sinus gland extirpation or by repeated injections of 20
      hydroxyecdysone. Manipulated males were sacrificed at premoult or early
      postmoult, and a reference population was sacrificed at intermoult.
      Differentially expressed genes among the four combinations of two induction
      methods and two moult stages were identified. Biologically interesting clusters
      revealing concurrently changing transcript expressions across treatments were
      selected, characterized by a general shift of expression throughout premoult and
      early postmoult vs. intermoult, or by different premoult vs. postmoult
      expressions. A number of genes were differentially expressed in 20
      hydroxyecdysone-injected crayfish vs. X-organ sinus gland extirpated males.

PMID- 18092999
TI  - Genetic exchange in 2La inversion heterokaryotypes of Anopheles gambiae.
AB  - In the malaria vector Anopheles gambiae, alternative arrangements of chromosome 2
      (2La and 2L+(a)) vary in relative frequency along clines of aridity, suggesting
      the action of natural selection on targets within the inversion. Our long term
      goal of detecting such targets depends in part on the level of genetic exchange
      between arrangements. Accordingly, we estimated recombination rates on 2L from
      the backcross progeny of 2La/+(a) heterokaryotypes and as a control, from 2L+(a)
      homokaryotypes. In homokaryotypes, the recombination rate was uniform at ~2.0
      centimorgans per megabase (cM/Mb). In heterokaryotypes, recombination within the
      rearranged region was reduced to < 0.5 cM/Mb, with slightly higher but
      nevertheless reduced levels (< 1.0 cM/Mb) flanking the rearrangement. Yet, gene
      exchange was recorded between nearly all markers, including those very near the
      distal inversion breakpoint. These results suggest that reduced recombination is
      a necessary but not sufficient mechanism for genetic isolation between
      alternative arrangements, and that the targets of natural selection can be
      identified against the different chromosomal backgrounds.

PMID- 18093000
TI  - Identification and molecular characterization of a novel protein Saglin as a
      target of monoclonal antibodies affecting salivary gland infectivity of
      Plasmodium sporozoites.
AB  - Molecular mechanisms underlying the interaction between malarial sporozoites and
      putative receptor(s) on the salivary glands of Anopheles gambiae remain largely
      unknown. In previous studies, a salivary gland protein of ~100 kDa was identified
      as a putative target based on recognition of the protein by a monoclonal antibody
      (mAb) 2A3 that caused a >/= 70% reduction in the average number of sporozoites
      per infected salivary gland when fed to mosquitoes. Using affinity purification
      we purified the target of this mAb from extracts of female A. gambiae salivary
      glands and it was found to be a novel protein by tandem mass spectrometric
      analysis. Biochemical and molecular characterization of the 100 kDa protein
      showed that this molecule, designated Saglin, exists as a disulphide-bonded
      homodimer of 50 kDa subunits. The ability to form homodimers was retained even in
      the recombinant Saglin expressed in mammalian cells (HEK293). The amino acid
      sequence of Saglin contains a signal peptide suggesting that Saglin is a secreted
      protein. If Saglin is indeed involved in the process of invasion of A. gambiae
      salivary glands by sporozoites of Plasmodium, it could provide a novel target for
      future investigations aimed at interruption of malaria transmission.

PMID- 18093001
TI  - Molecular cloning of a GABA receptor subunit from Laodelphax striatella (Fallen)
      and patch clamp analysis of the homo-oligomeric receptors expressed in a
      Drosophila cell line.
AB  - A cDNA encoding a gamma-aminobutyric acid (GABA) receptor subunit was cloned from
      the small brown planthopper Laodelphax striatella. The L. striatella GABA
      receptor subunit was found to have high amino acid sequence similarity to the bd
      type splice variant of the Drosophila GABA receptor Rdl subunit and several other
      GABA receptor subunits, with identities of over 70%. The cDNA was inserted into
      the expression vector pAc5.1-lac-Hygro. Clonal cell lines stably expressing homo
      oligomeric L. striatella GABA receptors were generated by transfecting the vector
      into D.mel-2 cells. Expression of functional GABA receptors in the cell lines was
      demonstrated by whole-cell patch clamp recordings. GABA induced inward currents
      with an EC(50) value of 29 microM and a Hill coefficient of 1.7. The GABA-evoked
      responses reversed close to the Nernst equilibrium potential for chloride ions.
      The amplitudes of agonist-induced currents were found to be in the order muscimol
      (100 microM) >/= GABA (100 microM) > isoguvacine (100 microM) > cis-4
      aminocrotonic acid (CACA) (100 microM) > 5-(4-piperidyl)-3-isoxazolol (4-PIOL) (1
      mM). Antagonists such as fipronil (100 nM), 4'-ethynyl-4-n
      propylbicycloorthobenzoate (EBOB) (100 nM), dieldrin (100 nM) and SR95531
      (gabazine) (1 microM) suppressed GABA-induced currents. The functional expression
      of a GABA receptor from an agricultural pest presents a unique opportunity to
      discover new molecules active at this important target site.

PMID- 18093002
TI  - X and Y chromosome inheritance and mixtures of rDNA intergenic spacer regions in
      Anopheles gambiae.
AB  - We observed Anopheles gambiae sensu stricto stocks that contained both Mopti (M)
      and Savanna (S) rDNA intergenic spacers (IGS). ASEMBO1 male IGS sequences
      consistently had a mixture. A diagnostic M and S Hha I restriction enzyme site in
      these fragments was concordant with two SNPs associated with M and S. Standard M
      and S stocks demonstrated X-chromosome-only inheritance of the rDNA form, but the
      ASEMBO1 males showed X and Y chromosome linkage of mixed rDNA. The metaphase Y
      chromosomes of ASEMBO1 contained a significantly larger amount of DNA relative to
      the X than a standard S stock. Analysis of wild A. gambiae males from the
      putative location of origin of the ASEMBO1 stock did not detect the same pattern
      of polymorphism observed in the laboratory stock but did detect heterogeneous
      arrays including some missing a diagnostic Hha I restriction site. These results
      demonstrate that M and S IGS types can occur within the rDNA arrays of a
      chromatid in laboratory A. gambiae stocks, and some A. gambiae s.s. have rDNA on
      the Y chromosome.

PMID- 18093003
TI  - Diverse Mariner-like elements in fig wasps.
AB  - Mariner transposable elements are widespread and diverse in insects. We screened
      10 species of fig wasps (Hymenoptera: Agaonidae) for mariner elements. All 10
      species harbour a large diversity of mariner elements, most of which have
      interrupted reading frames in the transposase gene region, suggesting that they
      are inactive and ancient. We sequenced two full-length mariner elements and found
      evidence to suggest that they are inserted in the genome at a conserved region
      shared by other hymenopteran taxa. The association between mariner elements and
      fig wasps is old and dominated by vertical transmission, suggesting that these
      'selfish genetic elements' have evolved to impart only very low costs to their
      hosts.

PMID- 18093004
TI  - Relish regulates expression of antimicrobial peptide genes in the honeybee, Apis
      mellifera, shown by RNA interference.
AB  - Relationships of immune genes in adult honeybees (Apis mellifera) were
      investigated using RNA interference (RNAi). Quantitative RT-PCR was applied to
      estimate gene expression and the extent of gene silencing. Relish is a
      transcription factor and forms an important part of the IMD signalling pathway.
      The expression of the immune gene Relish was significantly reduced by RNAi (ca.
      70%). The proposed regulation of antimicrobial peptide genes by Relish could be
      established for abaecin and hymenoptaecin. These two genes showed a reduction in
      gene expression to the same extent as Relish. However, the antimicrobial peptide
      gene defensin-1 was not affected which suggests defensin-1 is regulated by a
      different signalling pathway.

PMID- 18093005
TI  - Profiling infection responses in the haemocytes of the mosquito, Aedes aegypti.
AB  - Pathogens that infect and/or are transmitted by mosquitoes typically are exposed
      to the body cavity, and to haemocytes circulating therein, during development or
      dissemination. Aedes aegypti haemocytes produce a range of immune response
      related gene products, and an endpoint response of phagocytosis and/or
      melanization that is temporally and structurally distinct for the invading
      pathogen. Expressed sequence tags were generated from haemocyte libraries and
      then used to design oligonucleotide microarrays. Arrays were screened with
      haemocyte material collected 1-, 8- and 24-h post-inoculation with Escherichia
      coli or Micrococcus luteus bacteria. Data from these studies support the
      discovery of novel immune response-activated genes, provide an expanded
      understanding of antimicrobial peptide biology and highlight the coordination of
      immune factors that leads to an endpoint response.

PMID- 18093006
TI  - Nuclear mitochondrial-like sequences in ants: evidence from Atta cephalotes
      (Formicidae: Attini).
AB  - Nuclear mitochondrial-like sequences (numts) are copies of mitochondrial DNA that
      have migrated to the genomic DNA. We present the first characterization of numts
      in ants, these numts being homologues to a mitochondrial DNA fragment containing
      loci the 3' portion of the cytochrome oxidase I gene, an intergenic spacer, the
      tRNA leucine gene and the 5' portion of the cytochrome oxidase II gene. All 67
      specimens of Atta cephalotes (Hymenoptera: Formicidae: Attini) investigated had
      these homologues, which are within two monophyletic groups that we called numt1
      and numt2. Numt1 and numt2 sequences are less variable than mitochondrial
      sequences and released from the severe purifying selection constraining the
      evolution of mitochondrial genes. Their formation probably involved bottlenecks
      related to two distinct transfer events of ancient and fast evolving
      mitochondrial DNA fragments to comparative slowly evolving nuclear DNA regions.

PMID- 18093007
TI  - A mutation in the voltage-gated sodium channel gene associated with pyrethroid
      resistance in Latin American Aedes aegypti.
AB  - Pyrethroids are commonly used as mosquito adulticides and evolution of resistance
      to these compounds is a major threat to public health. 'Knockdown resistance' to
      pyrethroids (kdr) is frequently caused by nonsynonymous mutations in the voltage
      gated sodium channel transmembrane protein (para) that reduce pyrethroid binding.
      Early detection of kdr is critical to the development of resistance management
      strategies in mosquitoes including Aedes aegypti, the most prevalent vector of
      dengue and yellow fever viruses. Brengues et al. described seven novel mutations
      in hydrophobic segment 6 of domain II of para in Ae. aegypti. Assays on larvae
      from strains bearing these mutations indicated reduced nerve sensitivity to
      permethrin inhibition. Two of these occurred in codons Iso1011 and Val1016 in
      exons 20 and 21 respectively. A transition in the third position of Iso1011
      encoded a Met1011 replacement and a transversion in the second position of
      Val1016 encoded a Gly1016 replacement. We have screened this same region in 1318
      mosquitoes in 32 additional strains; 30 from throughout Latin America. While the
      Gly1016 allele was never detected in Latin America, we found two new mutations in
      these same codons. A transition in the first position of codon 1011 encodes a Val
      replacement while a transition in the first position of codon 1016 encodes an Iso
      replacement. We developed PCR assays for these four mutations that can be read
      either on an agarose gel or as a melting curve. Selection experiments, one with
      deltamethrin on a field strain from Santiago de Cuba and another with permethrin
      on a strain from Isla Mujeres, Mexico rapidly increased the frequency of the
      Iso1016 allele. Bioassays of F(3) offspring arising from permethrin susceptible
      Val1016 homozygous parents and permethrin resistant Iso1016 homozygous parents
      show that Iso1016 segregates as a recessive allele in conferring kdr. Analysis of
      segregation between alleles at the 1011 and 1016 codons in the F(3) showed a high
      rate of recombination even though the two codons are only separated by a ~250 bp
      intron. The tools and information presented provide a means for early detection
      and characterization of kdr that is critical to the development of strategies for
      resistance management.

PMID- 18093008
TI  - Tetracycline treatment influences mitochondrial metabolism and mtDNA density two
      generations after treatment in Drosophila.
AB  - Tetracycline is commonly used to clear Wolbachia from infected insects. Studies
      then compare specific biochemical and/or life-history traits between infected and
      uninfected individuals with the same genetic background. We investigated the
      potential for tetracycline to influence mitochondrial efficiency and
      mitochondrial (mt)DNA density two generations after treatment in Drosophila
      simulans. We observed that antibiotic treatment resulted in a decline in
      inorganic phosphate incorporated into ATP per mole of oxygen consumed (ADP:O
      ratio). Further, tetracycline treatment caused a significant increase in mtDNA
      density in naturally Wolbachia-uninfected but not in naturally Wolbachia-infected
      lines suggesting a dosage effect. These data suggest that the current practice of
      comparing Wolbachia-infected and Wolbachia-uninfected insects two generations
      after tetracycline treatment needs to be re-evaluated.

PMID- 18093010
TI  - Esthetic treatment modalities in men: psychologic aspects of male cosmetic
      patients.
AB  - Male cosmetic patients represent a growing population of individuals who can
      substantially benefit from well-chosen esthetic interventions. Understanding some
      of the unique aspects of the male psyche can result in more effective recruitment
      of male cosmetic patients and aid the clinician in helping these patients to
      choose appropriate interventions. Specific recommendations for the physician,
      staff, and office environment are provided. Illustrations of emotional and
      functional benefits are provided that can be shared with patients to enhance
      expectations and satisfaction with outcomes.

PMID- 18093011
TI  - Hand augmentation with Radiesse (Calcium hydroxylapatite).
AB  - The hand has remained a considerable treatment challenge, as new soft tissue
      fillers have arrived in the esthetic marketplace. The challenge has been the
      result of both the multiple visits required for treatment in, for example,
      autologous fat grafting and the simple management of pain in the innervated areas
      of the hand between the bones. This paper introduces a novel, noticeably less
      painful approach to treatment of the hand with calcium hydroxylapatite (CaHA;
      Radiesse, BioForm Medical, San Mateo, CA). Anesthetic is added to the compound
      prior to injection, resulting in a homogenous admixture of CaHA and anesthetic. A
      bolus of the mixture is injected into the skin, using tenting, and then spread
      throughout the hand. The result of this approach - mixing anesthetic with CaHA -
      is treatment that is easier to massage and disseminate, less painful to the
      patient than conventional hand injection, and characterized by less swelling and
      bruising, with minimal post-treatment downtime.

PMID- 18093012
TI  - New fillers for the new man.
AB  - Two new collagen-based lidocaine-containing dermal fillers, ArteSense/ArteFill
      (Artes Medical, San Diego, CA) and Evolence (Colbar LifeScience Ltd., Herzliya,
      Israel), have proved to be of particular interest to men, many of whom seek a
      long-lasting or permanent correction. ArteFill has been available in the United
      States since 2006, and it is expected that Evolence will reach the American
      market in 2008. The properties of the two products will be described, and
      experience based on the administration of many hundreds of syringes of both
      products by a Canadian dermatologist will be detailed here, with tips and
      precautions to optimize patient outcomes.

PMID- 18093013
TI  - Hyaluronic acid fillers for the male patient.
AB  - The male cosmetic population has been more timid over the years for procedures
      for facial rejuvenation. Only with the advent of minimally invasive procedures
      such as Botox and fillers have men begun to participate in cosmetic treatments.
      Men come with esthetic needs and areas of treatment different from women and
      require a different array of injectable fillers for each of these problems.
      Wrinkle ablation, volumization, and sculpting facial contours are procedures with
      the various agents available.

PMID- 18093015
TI  - Nonablative laser rejuvenation in men.
AB  - As our culture increasingly emphasizes youth and virility in the workplace, men
      have become interested in enhancing their appearance. Once confined to a small
      number of "progressive" urban patients, the ever-enlarging buffet of minimally
      invasive procedures has broadened the appeal for laser rejuvenation. Although
      most procedures are gender neutral, there are sex-specific characteristics that
      should be considered in designing logical laser strategies for men. In this
      review, the major categories of rejuvenation are examined in a modality- and
      application-specific manner. When possible, settings are discussed for particular
      devices. The reader should be aware, however, that "go-by" recipes, although
      enticing for the novice, should only be applied within the context of
      identifiable tissue endpoints and with properly functioning equipment. The best
      settings are those that achieve desired results for a specific device, and
      ultimately, experience is the best guide for optimal parameter selection.

PMID- 18093014
TI  - Botox in men.
AB  - Men have a growing interest in cosmetic dermatologic treatments. Botulinum toxin
      type A (BTX-A) treatment offers a minimally invasive approach to improving facial
      lines and is often the first cosmetic procedure chosen by male patients. In
      general, men can be treated with the same techniques as women, but often require
      more units of BTX-A. Glabellar lines in the male have been the most well-studied
      with a recommended starting dose of 40 U. Some men may require up to 80 U in the
      glabellar complex. The most common cause of an inadequate result in male patients
      is under-dosing. Forehead lines require care, as many men with horizontal lines
      have low-positioned eyebrows, and excessive relaxation of the lower frontalis
      muscle can drop their brows further. Special consideration should be given to the
      male brow when treating men. Lateral orbital lines can be treated with a starting
      dose of 15 U per crow's foot. Men may need additional injections to the
      orbicularis oculi muscle as many men have a broad circumferential orbicularis.
      The lower face is amenable to BTX-A treatment in men. BTX-A can be used to reduce
      axillary sweating and improve armpit odor. BTX-A shows promise in treating benign
      prostatic hyperplasia, and may in the future become a first-line treatment.

PMID- 18093016
TI  - Nonablative fractional resurfacing in the male patient.
AB  - Skin resurfacing can be divided into nonablative, nonablative fractional,
      ablative fractional, and traditional ablative categories. Nonablative
      technologies have yielded inconsistent and unimpressive results, whereas ablative
      technologies, although generally clinically effective, are losing momentum as a
      result of prolonged recovery times, risks for hypopigmentation, limitation in
      lighter skin types, and the production of unnatural sheen and texture to the
      skin. Fractional resurfacing can produce the safety of nonablative technologies
      and the efficacy of traditional ablative resurfacing. Nonablative fractional
      resurfacing is the most widely studied of fractional technologies allowing for
      nonablative tissue coagulation, creation of microthermal zones, and resurfacing
      with extrusion and replacement of damaged tissue with rapid re-epithelialization.
      This article will review nonablative fractional resurfacing with 1550-nm laser in
      the male patient.

PMID- 18093017
TI  - Basic hair transplantation: 2007.
AB  - The most common form of hair loss is androgenic alopecia that affects at least
      half of the male population by age 50 is speculated to be caused by a change in
      the balance of androgen hormones. Male hair loss occurs in a characteristic
      pattern of decreased hair growth where hair becomes progressively finer, less
      pigmented, ceasing growth completely, and then becoming dislodged from the scalp.
      Hair loss to some patients is a serious issue that can impart a social and
      psychologic impact on their life. Hair restoration and transplantation have the
      potential to provide a solution for this problem; however, it is not effective
      for every patient. This review article looks at past hair transplantation
      techniques and studies that have provided the basis for current procedures and
      new research at how to target successful results.

PMID- 18093018
TI  - The new laser liposuction for men.
AB  - Laser-assisted lipolysis with a medium-pulsed 1064-nanometer neodymium-doped
      yttrium aluminum garnet (Nd:YAG) system is a new FDA-approved method of removing
      localized areas of fat with the added benefit of skin tightening. This new method
      is particularly useful in treating the lower abdomen and submental areas where
      skin laxity may occur after the removal of adipose tissue. In addition, decreased
      bruising and scrotal edema after treating men is possible with use of the
      tumescent technique and the added benefit of coagulation produced by the laser.
      Experience in treating men with this modality is reviewed.

PMID- 18093019
TI  - Skin care for men and its marketing.
AB  - Male patients may be the forgotten consumer when it comes to cosmetics. There are
      many procedures that are marketed to men and can be successful, including laser
      hair removal, liposuction, Botox and fillers. With appropriate marketing efforts,
      the introduction and integration of a male-oriented cosmetic product branch
      within a practice can be effectively established. Methods of marketing include in
      house efforts as well as media placements that allow male and female ads to be
      essentially co-promoted and potentially solitary ads aimed toward cosmetic sales.
      Various product types and problem-related cosmetic information is given in this
      article.

PMID- 18093020
TI  - Editorial: Answering questions in developmental science: separating the wheat
      from the chaff.

PMID- 18093021
TI  - Research Review: genetic vulnerability or differential susceptibility in child
      development: the case of attachment.
AB  - Gene-environment interactions interpreted in terms of differential susceptibility
      may play a large part in the explanation of individual differences in human
      development. Reviewing studies on the behavioral and molecular genetics of
      attachment, we present evidence for interactions between genetic and
      environmental factors explaining individual differences in attachment security
      and disorganization. In particular, the DRD4 7-repeat polymorphism seems
      associated with an increased risk for disorganized attachment, but only when
      combined with environmental risk. Gene-environment (G x E) interactions may be
      interpreted as genetic vulnerability or differential susceptibility. We found
      support for the differential susceptibility hypothesis predicting not only more
      negative outcomes for susceptible children in unfavorable environments, but also
      positive outcomes for susceptible children in favorable environments.

PMID- 18093024
TI  - Reading exposure: a (largely) environmental risk factor with environmentally
      mediated effects on reading performance in the primary school years.
AB  - BACKGROUND: It is widely believed that there are reciprocal links between reading
      achievement and reading exposure: children who read more do better at reading,
      and reading achievement itself promotes reading. We tested the hypotheses that
      these links arise because children's genetically influenced reading performance
      is correlated with their leisure-time reading exposure, and reading exposure, in
      turn, may have an environmentally mediated effect on later reading performance.
      METHOD: The sample consisted of 3039 twin pairs from the UK Twins Early
      Development Study (TEDS). Reading exposure was assessed at age 10 using the
      Author Recognition Test (ART). Reading performance was assessed at ages 7 and 12
      using the Test of Word Reading Efficiency (TOWRE). RESULTS: ART scores were
      moderately correlated with TOWRE scores at ages 7 and 12. Shared environmental
      variance in 7-year TOWRE performance accounted for most of the contribution made
      by 7-year TOWRE scores to the prediction of 10-year ART scores. Genetic
      influences on ART scores were modest, but this genetic variance almost completely
      reflected genetic variance in 7-year TOWRE scores. After controlling for genetic
      and environmental influences that overlapped between 7-year TOWRE and 10-year ART
      scores, there was evidence for a separate link between 10-year ART and 12-year
      TOWRE that was due to shared environmental influences. CONCLUSIONS: Genetic
      influences on early reading achievement contribute to later propensities to seek
      out reading experiences that might, in turn, reciprocally influence reading
      achievement through shared environmental paths.

PMID- 18093022
TI  - What do childhood anxiety disorders predict?
AB  - BACKGROUND: Few longitudinal studies of child and adolescent psychopathology have
      examined the links between specific childhood anxiety disorders and adolescent
      psychiatric disorder. In this paper we test the predictive specificity of
      separation anxiety disorder (SAD), overanxious disorder (OAD), generalized
      anxiety disorder (GAD), and social phobia. METHODS: Data come from the Great
      Smoky Mountains Study (GSMS). A representative population sample of children-
      ages 9, 11, and 13 years at intake--was followed to age 19. Diagnoses of both
      childhood (before age 13 years) and adolescent psychiatric disorders (age 13 to
      19 years) were available from 906 participants. RESULTS: Childhood SAD predicted
      adolescent SAD, whereas OAD was associated with later OAD, panic attacks,
      depression and conduct disorder (CD). GAD was related only to CD. Social phobia
      in childhood was associated with adolescent OAD, social phobia, and attention
      deficit/hyperactivity disorder (ADHD). CONCLUSIONS: Anxiety disorders in
      childhood are predictors of a range of psychiatric disorders in adolescence. It
      appears that children meriting a well-defined diagnosis are missed by the current
      rules for the diagnosis of GAD. Future studies should examine whether OAD
      deserves reconsideration as a nosological entity.

PMID- 18093023
TI  - Feeling anxious: a twin study of panic/somatic ratings, anxiety sensitivity and
      heartbeat perception in children.
AB  - BACKGROUND: Little is known about mechanisms of genetic influence on panic,
      particularly in childhood. Cognitive theories of panic disorder highlight
      threatening interpretations of physical sensations, and increased awareness of
      such sensations. Specifically, anxiety sensitivity (AS) and heartbeat perception
      (HBP) have been associated with panic in adults and children. We examined genetic
      and environmental influences on childhood AS, HBP, panic/somatic ratings, and
      their associations. METHODS: Self-ratings of AS and DSM-based anxiety (including
      panic/somatic items) were obtained from 300 eight-year-old twin pairs (600
      individuals), selected for mother-rated child anxiety at age 7. HBP was also
      assessed. RESULTS: Panic/somatic ratings were significantly correlated with both
      AS (r = .55) and continuous HBP error scores (r = -.13). AS and HBP scores showed
      significantly greater correlations with panic/somatic ratings than with all other
      anxiety scales, except for HBP and school anxiety. Genetic influences on
      panic/somatic ratings were modest (15%), and moderate for both AS (37%), and HBP
      (30%). Non-shared environmental influences were substantial. The genetic
      correlations between panic/somatic ratings and both AS and HBP error scores were
      .98 (95% CI: .74-1.00) and -.46 (95% CI: -1.00-1.00) respectively. CONCLUSIONS:
      Self-ratings of panic and AS overlap genetically. Future research should consider
      whether AS mediates genetic risk for panic disorder.

PMID- 18093025
TI  - Early adolescent outcomes of institutionally deprived and non-deprived adoptees.
      III. Quasi-autism.
AB  - BACKGROUND: Some young children reared in profoundly depriving institutions have
      been found to show autistic-like patterns, but the developmental significance of
      these features is unknown. METHODS: A randomly selected, age-stratified, sample
      of 144 children who had experienced an institutional upbringing in Romania and
      who were adopted by UK families was studied at 4, 6, and 11 years, and compared
      with a non-institutionalised sample of 52 domestic adoptees. Twenty-eight
      children, all from Romanian institutions, for whom the possibility of quasi
      autism had been raised, were assessed using the Autism Diagnostic Interview
      Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) at the age
      of 12 years. RESULTS: Sixteen children were found to have a quasi-autistic
      pattern; a rate of 9.2% in the Romanian institution-reared adoptees with an IQ of
      at least 50 as compared with 0% in the domestic adoptees. There were a further 12
      children with some autistic-like features, but for whom the quasi-autism
      designation was not confirmed. The follow-up of the children showed that a
      quarter of the children lost their autistic-like features by 11. Disinhibited
      attachment and poor peer relationships were also present in over half of the
      children with quasi-autism. CONCLUSIONS: The findings at age 11/12 years
      confirmed the reality and clinical significance of the quasi-autistic patterns
      seen in over 1 in 10 of the children who experienced profound institutional
      deprivation. Although there were important similarities with 'ordinary' autism,
      the dissimilarities suggest a different meaning.

PMID- 18093026
TI  - Children's perceptions of neighbourhood trustworthiness and safety and their
      mental health.
AB  - BACKGROUND: Many studies have described associations between adult psychiatric
      disorder among adults and their biographic, socio-demographic and social capital
      characteristics. Fewer studies have focused on children, and most of these have
      looked at structural indicators of the neighbourhood. Our objective was to
      examine one aspect of social capital--perceived neighbourhood trust and safety in
      relation to childhood psychopathology. METHODS: Data on childhood psychopathology
      and perceived neighbourhood trust and safety were obtained on 3,340 11 to 16-year
      olds included in a large survey of the mental health carried out in 426 postal
      sectors in Great Britain. Data were collected on biographic and socio-demographic
      characteristics of the child and the family, measures of social capital and
      neighbourhood prosperity. We entered all these variables into a logistic
      regression analysis to establish the strength of association between perceived
      neighbourhood trust and safety separately for emotional and conduct disorders.
      RESULTS: Children's perception of their neighbourhoods in terms of the
      trustworthiness or honesty of the people who live there or feeling safe walking
      alone had a strong association with childhood psychopathology, particularly
      emotional disorders, rather than the nature of the neighbourhood itself.
      Children's behaviour, however, such as going to the park or shops alone, did not
      vary by measures of childhood psychopathology. CONCLUSIONS: Regeneration of less
      prosperous neighbourhoods is likely to increase children's positive perceptions
      of trust, honesty and safety which in turn can have a positive effect on their
      mental health.

PMID- 18093027
TI  - The effect of social disadvantage on motor development in young children: a
      comparative study.
AB  - BACKGROUND: Empirical research suggests that social disadvantage has a negative
      effect on the development of language, and related cognitive skills such as
      reading. There is, however, no corresponding body of research on the impact of
      social disadvantage on motor development. The primary purpose of this study was
      to investigate the impact of social disadvantage on motor development in young
      children. In addition, we explored a possible link between an early neuromotor
      indicator and attainments in language, and reading. METHODS: The Northern Ireland
      Multiple Deprivation Measure was used to identify two contrasting districts based
      on a composite measure of social disadvantage. We investigated the effect of
      social disadvantage on the motor attainments of a sample of 239 children aged 4-5
      years, and 276 children aged 7-8 years attending mainstream schools in each
      district using a standardised motor assessment battery, and a motor
      neurodevelopmental measure. We used standardised receptive language and reading
      assessments to evaluate possible associations between motor and language/reading
      attainments. RESULTS: There was a significant negative effect of social
      disadvantage on motor skills, for both age groups, and for both males and
      females. A similar negative effect of social disadvantage on attainments in
      language, and reading was also found. Children from areas of social disadvantage
      had significant deficits in motor and receptive language attainments relative to
      their more advantaged peers. In addition, we revealed a significant predictive
      relationship between a neurodevelopmental measure of early motor development and
      reading attainment. CONCLUSIONS: Children growing up in socially disadvantaged
      areas may be at particular risk of motor, including neurodevelopmental, delay, as
      well as language and reading difficulties. The determinants of motor and
      neuromotor deficits in children from disadvantaged backgrounds should be
      explored, and the relationship between early neuromotor development and
      language/reading development requires further investigation.

PMID- 18093028
TI  - Inter-parental conflict and children's academic attainment: a longitudinal
      analysis.
AB  - BACKGROUND: Previous research suggests a link between inter-parental conflict and
      children's psychological development. Most studies, however, have tended to focus
      on two broad indices of children's psychological adaptation (internalizing
      symptoms and externalizing problems) in considering the effects of inter-parental
      conflict on children's development. The present longitudinal study extends this
      body of research by considering the impact of inter-parental conflict on
      children's low academic attainment among a sample of 230 schoolchildren (age 11
      13 years) living in the United Kingdom. METHOD: Controlling for teacher reports
      of children's initial levels of aggression (Time 1), the proposed theoretical
      model linked parent and child reports of inter-parental conflict at Time 1 (1999)
      to children's perceptions of negative parent-child relations, appraisals of self
      blame for marital conflict and teacher reports of children's aggressive behavior
      at Time 2 (2000), which in turn were linked to children's performance on
      standardized academic tests (English, Math, Science) at Time 3 (2001). Structural
      equation modeling was used to test all hypothesized relations in the proposed
      theoretical model. RESULTS: Support was found for the role of children's self
      blaming attributions for parents' marital arguments, not negative parenting
      behavior, as a mechanism through which variation in their academic attainment is
      explained. CONCLUSIONS: Contrary to the focus emphasized in most current family
      and school-based intervention programs, findings suggest that the attributional
      processes engendered in children who live in households marked by high levels of
      inter-parental conflict and hostility have important implications for their long
      term academic success.

PMID- 18093029
TI  - Parenting, attention and externalizing problems: testing mediation
      longitudinally, repeatedly and reciprocally.
AB  - BACKGROUND: Building on prior work, this paper tests, longitudinally and
      repeatedly, the proposition that attentional control processes mediate the effect
      of earlier parenting on later externalizing problems. METHODS: Repeated
      independent measurements of all three constructs--observed parenting, computer
      tested attentional control and adult-reported externalizing problems--were
      subjected to structural equation modeling using data from the large-scale
      American study of child care and youth development. RESULTS: Structural equation
      modeling indicated (a) that greater maternal sensitivity at two different ages
      (54 months, approximately 6 years) predicted better attentional control on the
      Continuous Performance Test (CPT) of attention regulation two later ages (
      approximately 6/9 years); (2) that better attentional control at three different
      ages (54 months, approximately 6/9 years) predicted less teacher-reported
      externalizing problems at three later ages ( approximately 6/8/10 years); and (3)
      that attentional control partially mediated the effect of parenting on
      externalizing problems at two different lags (i.e., 54 months--> approximately 6
      years--> approximately 8 years; approximately 6 years--> approximately 9 years-->
      approximately 10 years), though somewhat more strongly for the first.
      Additionally, (4) some evidence of reciprocal effects of attentional processes on
      parenting emerged (54 months--> approximately 6 years; approximately 6 years-->
      approximately 8 years), but not of problem behavior on attention. CONCLUSIONS:
      Because attention control partially mediates the effects of parenting on
      externalizing problems, intervention efforts could target both parenting and
      attentional processes.

PMID- 18093030
TI  - Social maturity and theory of mind in typically developing children and those on
      the autism spectrum.
AB  - BACKGROUND: Results of several studies using the Vineland scale to explore links
      between social behavior and theory of mind (ToM) have produced mixed results,
      especially for children on the autism spectrum. The present pair of studies
      developed a psychometrically sound, age-referenced measure of social maturity to
      explore these issues further. METHOD: In Study 1, 37 typically developing
      preschoolers took a battery of standard false belief tests of ToM and were rated
      by their teachers on a newly developed age-referenced social maturity scale with
      7 items. In Study 2, a further group of 43 children aged 4 to 12 years (13 with
      autism, 14 with Asperger's disorder and 16 with typical development) took part in
      the same procedure. RESULTS: In Study 1, ToM was found to predict typical
      preschoolers' social maturity independently of age and verbal maturity. In Study
      2, children with autism scored below age-matched and younger typical developers
      in both ToM and social maturity. Those with Asperger's disorder did well on ToM
      but poorly on social maturity. Study 2 replicated Study 1's finding (for typical
      children and for the full sample) that ToM was linked with social maturity
      independently of age and verbal ability, although the link was not independent of
      autism diagnosis. CONCLUSIONS: Teachers are capable of rating children's social
      behavior with peers as advanced, on-time or delayed for their age. Suggestive
      links between these ratings and ToM require further investigation, especially
      among children on the autism spectrum.

PMID- 18093031
TI  - Structural brain abnormalities in adolescents with autism spectrum disorder and
      patients with attention deficit/hyperactivity disorder.
AB  - BACKGROUND: Although autism spectrum disorder (ASD) and attention
      deficit/hyperactivity disorder (ADHD) are two distinct neurodevelopmental
      diseases, they share behavioural, neuropsychological and neurobiological
      characteristics. For the identification of endophenotypes across diagnostic
      categories, further investigations of phenotypic overlap between ADHD and autism
      at the behavioural, neurocognitive, and brain levels are needed. METHODS: We
      examined regional grey matter differences and similarities in children and
      adolescents with ASD and ADHD in comparison to healthy controls using structural
      magnetic resonance imaging (MRI) and voxel-based morphometry. RESULTS: With
      regard to clinical criteria, the clinical groups did not differ with respect to
      ADHD symptoms; however, only patients with ASD showed deficits in social
      communication and interaction, according to parental rating. Structural
      abnormalities across both clinical groups compared to controls became evident as
      grey matter reductions in the left medial temporal lobe and as higher grey matter
      volumes in the left inferior parietal cortex. In addition, autism-specific brain
      abnormalities were found as increased grey matter volume in the right
      supramarginal gyrus. CONCLUSIONS: While the shared structural deviations in the
      medial temporal lobe might be attributed to an unspecific delay in brain
      development and might be associated with memory deficits, the structural
      abnormalities in the inferior parietal lobe may correspond to attentional
      deficits observed in both ASD and ADHD. By contrast, the autism-specific grey
      matter abnormalities near the right temporo-parietal junction may be associated
      with impaired 'theory of mind' abilities. These findings shed some light on both
      similarities and differences in the neurocognitive profiles of ADHD and ASD
      patients.

PMID- 18093032
TI  - Inpatient treatment in child and adolescent psychiatry--a prospective study of
      health gain and costs.
AB  - BACKGROUND: Inpatient treatment is a complex intervention for the most serious
      mental health disorders in child and adolescent psychiatry. This is the first
      large-scale study into its effectiveness and costs. Previous studies have been
      criticised for methodological weaknesses. METHODS: A prospective cohort study,
      including economic evaluation, conducted in 8 UK units (total n = 150) with one
      year follow-up after discharge. Patients acted as their own controls. Outcome
      measurement was the clinician-rated Childhood Global Assessment Scale (CGAS);
      researcher-rated health needs assessment; parent- and teacher-rated
      symptomatology. RESULTS: We found a significant (p < .001) and clinically
      meaningful 12-point improvement in CGAS following mean 16.6 week admission
      (effect size .92); this improvement was sustained at 1 year follow-up.
      Comparatively, during the mean 16.4 week pre-admission period there was a 3.7
      point improvement (effect size .27). Health needs assessment showed similar gain
      (p < .001, effect size 1.25), as did teacher- and parent-rated symptoms.
      Improvement was found across all diagnoses. Longer stays, positive therapeutic
      alliance and better premorbid family functioning independently predicted better
      outcome. Mean cost of admission was pound 24,100; pre-admission and post
      discharge support costs were similar. CONCLUSIONS: Inpatient treatment is
      associated with substantive sustained health gain across a range of diagnoses.
      Lack of intensive outpatient-treatment alternatives limits any unqualified
      inference about causal effects, but the rigour of measurement here gives the
      strongest indication to date of the positive impact of admission for complex
      mental health problems in young people.

PMID- 18093033
TI  - Use of anti-inflammatory medication in healthy athletes - no pain, no gain?

PMID- 18093034
TI  - Pharmaceutical treatment of asthma symptoms in elite athletes - doping or
      therapy?
AB  - Asthma, exercise-induced bronchoconstriction, and airway hyper-responsiveness are
      often found in elite athletes, perhaps as a consequence of their sport or maybe
      because asthma is a common disorder in young adults. Inhaled beta2-agonists (IBA)
      are frequently used in elite athletes, but due to regulations introduced by the
      International Olympic Committee, the use of anti-asthmatic therapy might change.
      Drugs that make ergogenic effect persist are prohibited in all athletes, whether
      or not they take part in competitions and systemic steroids and beta2-agonists
      are among such drugs. On the other hand, opinion is more divided about the use of
      inhaled corticosteroids (ICS) and IBA. In humans, no effect has been found on the
      oxygen uptake, performance or distance run with therapeutic doses of IBA, either
      in asthmatics or non-asthmatics, whereas others report an ergogenic effect and
      better lung function of high doses of a beta2-agonist in non-asthmatics. Anti
      asthmatic treatment is necessary for asthmatics, but should not be used by non
      asthmatic elite athletes due to both possible systemic effects and furthermore,
      side effects of both ICS and IBA.

PMID- 18093036
TI  - Pregnancy intentions and happiness among pregnant black women at high risk for
      adverse infant health outcomes.
AB  - CONTEXT: Unintended pregnancy is associated with risk behaviors and increased
      morbidity or mortality for mothers and infants, but a woman's feelings about
      pregnancy may be more predictive of risk and health outcomes than her intentions.
      METHODS: A sample of 1,044 black women who were at increased risk were enrolled
      at prenatal care clinics in the District of Columbia in 2001-2003. Bivariate and
      multivariate analyses assessed associations between pregnancy intentions or level
      of happiness about being pregnant and multiple psychosocial and behavioral risk
      factors, and identified correlates of happiness to be pregnant. RESULTS:
      Pregnancy intentions and happiness were strongly associated, but happiness was
      the better predictor of risk. Unhappy women had higher odds than happy women of
      smoking, being depressed, experiencing intimate partner violence, drinking and
      using illicit drugs (odds ratios, 1.7-2.6). The odds of being happy were reduced
      among women who had other children or a child younger than two, who were single
      or did not have a current partner, who had had more than one sexual partner in
      the past year and who reported that the baby's father did not want the pregnancy
      (0.3-0.6). In contrast, the odds of being happy were elevated among women who had
      better coping strategies (1.03), who had not used birth control at conception
      (1.6) and who had 1-2 household members, rather than five or more (2.1).
      CONCLUSIONS: Additional psychosocial screening for happiness about being pregnant
      and for partner characteristics, particularly the father's desire to have this
      child, may help improve prenatal care services and prevent adverse health
      outcomes.

PMID- 18093037
TI  - The quality of family planning services in the United States: findings from a
      literature review.
AB  - CONTEXT: Family planning services are frequently used and important services for
      American women, yet little is known about their quality. Service quality has
      important implications for women's reproductive health. If women do not receive
      adequate information and tools, and learn appropriate skills, from their
      providers, they may be hampered in their efforts to control their fertility.
      METHODS: A variety of strategies, including database, journal and Internet
      searches, were used to identify published and unpublished U.S. studies on family
      planning service quality that came out between 1985 and 2005. Studies were
      categorized by their focus, and key points of their methodologies and findings
      were assessed. RESULTS: Twenty-nine studies were identified, most of which were
      based on client surveys. Most conceptualized quality as a multidimensional
      construct, but a uniform definition of quality is lacking, and the domains
      studied have not been consistent. The available studies focus on four areas:
      assessments of quality, its correlates, its consequences for client behavior and
      attitudes, and clients' values and preferences regarding services. Relations
      between clients and service facility staff have typically been rated favorably,
      but communication, patient-centeredness and efficiency have been rated more
      poorly. Service quality varies by characteristics of the facility, provider,
      client and visit. Research on the consequences of service quality for clients'
      contraceptive behavior or risk of unintended pregnancy has been very limited and
      yielded mixed results. CONCLUSIONS: Studies that assess service quality need
      stronger designs and greater consistency in measures used so that results are
      comparable.

PMID- 18093038
TI  - Legal abortion worldwide: incidence and recent trends.
AB  - CONTEXT: Information on abortion levels and trends can inform research and
      policies affecting maternal and reproductive health, but the incidence of legal
      abortion has not been assessed in nearly a decade. METHODS: Statistics on legal
      abortions in 2003 were compiled for 60 countries in which the procedure is
      broadly legal, and trends were assessed where possible. Data sources included
      published and unpublished reports from official national reporting systems,
      questionnaires sent to government agencies and nationally representative
      population surveys. The completeness of country estimates was assessed by
      officials involved in data collection and by in-country and regional experts.
      RESULTS: In recent years, more countries experienced a decline in legal abortion
      rates than an increase, among those for which statistics are complete and trend
      data are available. The most dramatic declines were in Eastern Europe and Central
      Asia, where rates remained among the highest in the world. The highest estimated
      levels were in Armenia, Azerbaijan and Georgia, where surveys indicate that women
      will have close to three abortions each, on average, in their lifetimes. The U.S.
      abortion rate dropped by 8% between 1996 and 2003, but remained higher than rates
      in many Northern and Western European countries. Rates increased in the
      Netherlands and New Zealand. The official abortion rate declined by 21% over
      seven years in China, which accounted for a third of the world's legal abortions
      in 1996. Trends in the abortion rate differed across age-groups in some
      countries. CONCLUSIONS: The abortion rate varies widely across the countries in
      which legal abortion is generally available and has declined in many countries
      since the mid-1990s.

PMID- 18093039
TI  - The association of health insurance with use of prescription contraceptives.
AB  - CONTEXT: Given that substantial proportions of women of reproductive age lack
      health insurance coverage, it is important to assess whether lack of insurance is
      associated with the use of prescription contraceptives, which are the most
      expensive but also the most effective methods for preventing pregnancy. METHODS:
      Data from 26,674 females aged 18-44 who participated in the 2002 Behavioral Risk
      Factor Surveillance System survey (representing more than 25 million women in the
      U.S. population) were used to assess risk of unintended pregnancy, prescription
      contraceptive use and health insurance status. Logistic regression models tested
      the likelihood of prescription contraceptive use among insured versus uninsured
      respondents after controlling for socioeconomic characteristics and self-reported
      overall health. RESULTS: A significantly higher proportion of insured women than
      of uninsured women reported use of prescription contraceptives (54% vs. 45%). In
      multiple regression analysis, women lacking health insurance were 30% less likely
      to report using prescription contraceptive methods than were women with private
      or public health insurance. Results were similar across racial, age and income
      subgroups. CONCLUSIONS: Lack of health insurance is associated with reduced use
      of prescription contraceptives. Universal insurance coverage is needed to ensure
      access to the most effective contraceptive methods for all women in need.

PMID- 18093040
TI  - Predictors of STDs among Asian and Pacific Islander young adults.
AB  - CONTEXT: Limited information is available on factors associated with STDs among
      Asian and Pacific Islander young adults. Such information is vital to developing
      effective interventions to reduce STDs within this group. METHODS: Data were
      derived from the National Longitudinal Study of Adolescent Health, Wave 3; the
      sample consisted of 605 female and 578 male Asian and Pacific Islander young
      adults. Logistic regression analysis was used to assess factors associated with
      ever having had an STD. RESULTS: Thirteen percent of females and 4% of males had
      ever had an STD. Among those who had had an STD, 75% were female, 9% had ever
      been paid for sex, 31% had had sex before age 15 and 55% had had multiple sex
      partners in the previous 12 months. Being female (odds ratio, 4.1), being Indian
      (compared with being Filipino; 4.8), having ever been paid money for sex (4.7)
      and having had more than one sex partner in the past 12 months (2.5) were
      associated with increased odds of having had an STD diagnosis. The more
      respondents believed that STDs were responsive to treatment, the greater their
      odds of having had an STD (2.3); the more they believed that STDs had negative
      consequences for a relationship, the lower their odds of having had an STD (0.7).
      CONCLUSIONS: Asian and Pacific Islander women and Indians are priority groups for
      both research and clinical attention; prevention efforts to reduce STDs should be
      tailored to these groups. Clinicians working with Asians and Pacific Islanders
      need to focus on clients' number of sexual partners and health-related beliefs.

PMID- 18093041
TI  - The pleasure deficit: revisiting the "sexuality connection" in reproductive
      health.

PMID- 18093042
TI  - Probabilistic fault tree analysis of a radiation treatment system.
AB  - Inappropriate administration of radiation for cancer treatment can result in
      severe consequences such as premature death or appreciably impaired quality of
      life. There has been little study of vulnerable treatment process components and
      their contribution to the risk of radiation treatment (RT). In this article, we
      describe the application of probabilistic fault tree methods to assess the
      probability of radiation misadministration to patients at a large cancer
      treatment center. We conducted a systematic analysis of the RT process that
      identified four process domains: Assessment, Preparation, Treatment, and Follow
      up. For the Preparation domain, we analyzed possible incident scenarios via fault
      trees. For each task, we also identified existing quality control measures. To
      populate the fault trees we used subjective probabilities from experts and
      compared results with incident report data. Both the fault tree and the incident
      report analysis revealed simulation tasks to be most prone to incidents, and the
      treatment prescription task to be least prone to incidents. The probability of a
      Preparation domain incident was estimated to be in the range of 0.1-0.7% based on
      incident reports, which is comparable to the mean value of 0.4% from the fault
      tree analysis using probabilities from the expert elicitation exercise. In
      conclusion, an analysis of part of the RT system using a fault tree populated
      with subjective probabilities from experts was useful in identifying vulnerable
      components of the system, and provided quantitative data for risk management.

PMID- 18093043
TI  - Benchmark analysis for quantifying urban vulnerability to terrorist incidents.
AB  - We describe a quantitative methodology to characterize the vulnerability of U.S.
      urban centers to terrorist attack, using a place-based vulnerability index and a
      database of terrorist incidents and related human casualties. Via generalized
      linear statistical models, we study the relationships between vulnerability and
      terrorist events, and find that our place-based vulnerability metric
      significantly describes both terrorist incidence and occurrence of human
      casualties from terrorist events in these urban centers. We also introduce
      benchmark analytic technologies from applications in toxicological risk
      assessment to this social risk/vulnerability paradigm, and use these to
      distinguish levels of high and low urban vulnerability to terrorism. It is seen
      that the benchmark approach translates quite flexibly from its biological roots
      to this social scientific archetype.

PMID- 18093044
TI  - What risks do people perceive in everyday life? A perspective gained from the
      experience sampling method (ESM).
AB  - The experience sampling method (ESM) was used to collect data from 74 part-time
      students who described and assessed the risks involved in their current
      activities when interrupted at random moments by text messages. The major
      categories of perceived risk were short term in nature and involved "loss of time
      or materials" related to work and "physical damage" (e.g., from transportation).
      Using techniques of multilevel analysis, we demonstrate effects of gender,
      emotional state, and types of risk on assessments of risk. Specifically, females
      do not differ from males in assessing the potential severity of risks but they
      see these as more likely to occur. Also, participants assessed risks to be lower
      when in more positive self-reported emotional states. We further demonstrate the
      potential of ESM by showing that risk assessments associated with current actions
      exceed those made retrospectively. We conclude by noting advantages and
      disadvantages of ESM for collecting data about risk perceptions.

PMID- 18093045
TI  - Symmetry, identifiability, and prediction uncertainties in multistage clonal
      expansion (MSCE) models of carcinogenesis.
AB  - Many models of exposure-related carcinogenesis, including traditional linearized
      multistage models and more recent two-stage clonal expansion (TSCE) models,
      belong to a family of models in which cells progress between successive stages
      possibly undergoing proliferation at some stages-at rates that may depend
      (usually linearly) on biologically effective doses. Biologically effective doses,
      in turn, may depend nonlinearly on administered doses, due to PBPK
      nonlinearities. This article provides an exact mathematical analysis of the
      expected number of cells in the last ("malignant") stage of such a "multistage
      clonal expansion" (MSCE) model as a function of dose rate and age. The solution
      displays symmetries such that several distinct sets of parameter values provide
      identical fits to all epidemiological data, make identical predictions about the
      effects on risk of changes in exposure levels or timing, and yet make
      significantly different predictions about the effects on risk of changes in the
      composition of exposure that affect the pharmacodynamic dose-response relation.
      Several different predictions for the effects of such an intervention (such as
      reducing carcinogenic constituents of an exposure) that acts on only one or a few
      stages of the carcinogenic process may be equally consistent with all
      preintervention epidemiological data. This is an example of nonunique
      identifiability of model parameters and predictions from data. The new results on
      nonunique model identifiability presented here show that the effects of an
      intervention on changing age-specific cancer risks in an MSCE model can be either
      large or small, but that which is the case cannot be predicted from
      preintervention epidemiological data and knowledge of biological effects of the
      intervention alone. Rather, biological data that identify which rate parameters
      hold for which specific stages are required to obtain unambiguous predictions.
      From epidemiological data alone, only a set of equally likely alternative
      predictions can be made for the effects on risk of such interventions.

PMID- 18093046
TI  - Analysis of the treatment, by the U.S. Department of Energy, of the FEP
      hydrothermal activity in the Yucca Mountain Performance Assessment.
AB  - The U.S. Code of Federal Regulations, 10 CFR Part 63, stipulates that the
      expected performance of the geological high-level nuclear waste repository must
      be demonstrated through a total system performance assessment (TSPA). The TSPA
      represents an analysis that identifies all features, events, and processes (FEPs)
      that might affect the disposal system and examines the effects of the identified
      FEPs upon the performance of the system. Secondary minerals from the thick
      unsaturated zone of Yucca Mountain were deposited from waters with temperatures
      up to 70-90 degrees C. U-Pb dating constrained the ages of the elevated
      temperatures to the period between 10 and 5-6 million years ago. Relatively
      youthful circulation of thermal waters (hydrothermal activity) would be of
      concern for the safety of the disposal facility. A phenomenological model was
      advanced by the U.S. Department of Energy (DOE), which proposed that the minerals
      were deposited by infiltrating meteoric waters that were heated upon contact with
      the bedrock; it was hypothesized that the latter was conductively heated by a
      shallow silicic magma body. The model rendered processes responsible for elevated
      water temperatures inconsequential for the safety of the proposed nuclear waste
      facility. However, attempts by DOE at validating the model by means of numeric
      thermal simulations and analogue system observations were unsuccessful.
      Regulations specify two criteria for exclusion of a FEP from consideration in the
      TSPA: low probability and low consequence. The lack of a plausible
      phenomenological model makes it impossible to apply either of these two criteria
      to the FEP Hydrothermal Activity. Despite the lack of a valid criterion for
      exclusion, it was excluded from the TSPA. Both the development of DOE's thermal
      model and the formal FEP analysis were associated with deviations from DOE's
      quality assurance regulations.

PMID- 18093047
TI  - Cryptosporidium and dairy cattle in the Catskill/Delaware watershed: a
      quantitative risk assessment.
AB  - We carried out a study to estimate the public health risk posed by dairy cattle
      located in New York City's Catskill/Delaware watershed, as measured by daily C.
      parvum-like oocyst loading. A Monte Carlo simulation model that takes into
      account the nature of the dairy cattle population within the target area, age
      specific incidence/prevalence rates, as well as differential fecal production and
      oocyst-shedding intensity rates was used to address the objectives. Additionally,
      the model was designed to distinguish between zoonotic and nonzoonotic
      species/genotypes of Cryptosporidium. Total estimated daily C. parvum-like oocyst
      shedding across all age/production categories was estimated at 4.15 x 10(10). The
      zoonotic C. parvum comprised 93.5% of this load. It was estimated that preweaned
      calves produce 99.5% of the total daily C. parvum ocyst burden. The recently
      described nonzoonotic C. bovis was estimated to have a daily load of 2.2 x 10(9)
      oocysts across all age/production strata. C. parvum deer-like genotype was
      estimated to have a total daily load of 1.3 x 10(9) oocysts. The results of this
      study support earlier assertions that strategies aimed at reducing the
      cryptosporidial risk posed by dairy cattle to public health will be most
      efficacious if aimed at preweaned calves.

PMID- 18093048
TI  - Estimation of benchmark dose as the threshold amount of alcohol consumption for
      blood pressure in Japanese workers.
AB  - In order to determine the threshold amount of alcohol consumption for blood
      pressure, we calculated the benchmark dose (BMD) of alcohol consumption and its
      95% lower confidence interval (BMDL) in Japanese workers. The subjects consisted
      of 4,383 males and 387 females in a Japanese steel company. The target variables
      were systolic, diastolic, and mean arterial pressures. The effects of other
      potential covariates such as age and body mass index were adjusted by including
      these covariates in the multiple linear regression models. In male workers,
      BMD/BMDL for alcohol consumption (g/week) at which the probability of an adverse
      response was estimated to increase by 5% relative to no alcohol consumption, were
      396/315 (systolic blood pressure), 321/265 (diastolic blood pressure), and
      326/269 (mean arterial pressures). These values were based on significant
      regression coefficients of alcohol consumption. In female workers, BMD/BMDL for
      alcohol consumption based on insignificant regression coefficients were 693/134
      (systolic blood pressure), 199/90 (diastolic blood pressure), and 267/77 (mean
      arterial pressure). Therefore, BMDs/BMDLs in males were more informative than
      those in females as there was no significant relationship between alcohol and
      blood pressure in females. The threshold amount of alcohol consumption determined
      in this study provides valuable information for preventing alcohol-induced
      hypertension.

PMID- 18093049
TI  - Hurricane destructive power predictions based on historical storm and sea surface
      temperature data.
AB  - Forecasting destructive hurricane potential is complicated by substantial,
      unexplained intraannual variation in storm-specific power dissipation index (PDI,
      or integrated third power of wind speed), and interannual variation in annual
      accumulated PDI (APDI). A growing controversy concerns the recent hypothesis that
      the clearly positive trend in North Atlantic Ocean (NAO) sea surface temperature
      (SST) since 1970 explains increased hurricane intensities over this period, and
      so implies ominous PDI and APDI growth as global warming continues. To test this
      "SST hypothesis" and examine its quantitative implications, a combination of
      statistical and probabilistic methods were applied to National Hurricane Center
      HURDAT best-track data on NAO hurricanes during 1880-2002, and corresponding
      National Oceanographic and Atmospheric Administration Extended Reconstruction SST
      estimates. Notably, hurricane behavior was compared to corresponding hurricane
      specific (i.e., spatiotemporally linked) SST; previous similar comparisons
      considered only SST averaged over large NAO regions. Contrary to the SST
      hypothesis, SST was found to vary in a monthly pattern inconsistent with that of
      corresponding PDI, and to be at best weakly associated with PDI or APDI despite
      strong correlation with corresponding mean latitude (R(2)= 0.55) or with combined
      mean location and a approximately 90-year periodic trend (R(2)= 0.70). Over the
      last century, the lower 75% of APDIs appear randomly sampled from a nearly
      uniform distribution, and the upper 25% of APDIs from a nearly lognormal
      distribution. From the latter distribution, a baseline (SST-independent)
      stochastic model was derived predicting that over the next half century, APDI
      will not likely exceed its maximum value over the last half century by more than
      a factor of 1.5. This factor increased to 2 using a baseline model modified to
      assume SST-dependence conditioned on an upper bound of the increasing NAO SST
      trend observed since 1970. An additional model was developed that predicts PDI
      statistics conditional on APDI. These PDI and APDI models can be used to estimate
      upper bounds on indices of hurricane power likely to be realized over the next
      century, under divergent assumptions regarding SST influence.

PMID- 18093050
TI  - CSP deposition to the alveolar region of the lung: implications of cigarette
      design.
AB  - Ventilated cigarettes were designed to reduce the levels of smoke under machine
      testing conditions; however, smokers alter their smoking pattern to compensate
      for the reduction in yields. A relative shift in incidence of lung cancer from
      the more central lung airways to the alveolar region has also been associated
      with ventilated cigarette use. Validated mathematical models indicate that
      particle deposition patterns in the lung depend on particle size and inhalation
      behavior, including inhalation volume, flow rate, and breath-hold time. This
      article finds that most mathematical models underpredict total cigarette smoke
      particulate (CSP) deposition in the lung, likely because they do not account for
      coagulation, hygroscopicity, and cloud dynamics, which may increase the effective
      particle diameter of CSP reaching the lung tissue. The models that include these
      processes indicate that puff volume would be unlikely to affect particle
      deposition in the lung, but puff time, inhalation depth, breath-hold time, and
      exhalation time may affect total deposition. Most compensation appears to occur
      through a combination of increased puff volume and puff flow, with possible
      increases in inhalation depth and breath-hold time. The complex interaction
      between the extent of cigarette ventilation, which can affect puffing/inhalation
      behavior, CSP concentration, and CSP size with CSP dose to the alveolar versus
      more central lung airways is described. Deposition efficiency in the alveoli
      could plausibly be increased through compensation, but it is still unclear
      whether compensation could sufficiently alter patterns of CSP deposition in the
      lung to elicit a shift in lung cancer sites.

PMID- 18093052
TI  - Intervening effects of knowledge, morality, trust, and benefits on support for
      animal and plant biotechnology applications.
AB  - Data from a regional Southwest telephone survey in the United States (N= 432)
      were used to examine the intervening effects of knowledge, morality, trust, and
      benefits on support for animal and plant biotechnology applications. Results
      showed that perceptions of agricultural biotechnologies varied by the two
      applications-animals and plants. Respondents reported higher opposition to the
      genetic modification of animals, which is consistent with prior research. Results
      also indicated that morality and perceived benefits directly affected support for
      both animal and plant applications, but trust and knowledge only had indirect
      effects. Morality and perceived benefits accounted for most of the variance
      explained among the intervening variables. The effects of trust were mediated
      through perceived benefits. The effects of knowledge on support were mediated
      primarily through trust. The influence of sociodemographic and consumer behavior
      variables varied by application. Results lend support to several theoretical
      notions. First, the significance of perceived benefits supports that there is an
      inverse relationship between benefits and risks. Second, moral objections may
      outweigh perceived benefits for specific applications, and the genetic
      modification of animals is deemed to be more morally unacceptable than the
      genetic modification of plants. These findings demonstrate the need to understand
      more thoroughly the moral and ethical issues surrounding novel technologies.
      Third, this research supports the claim that trust is not a powerful predictor of
      perceptions of technological products, which is contrary to most risk perception
      research.

PMID- 18093054
TI  - A quantitative microbial risk assessment model for Legionnaires' disease: animal
      model selection and dose-response modeling.
AB  - Legionnaires' disease (LD), first reported in 1976, is an atypical pneumonia
      caused by bacteria of the genus Legionella, and most frequently by L. pneumophila
      (Lp). Subsequent research on exposure to the organism employed various animal
      models, and with quantitative microbial risk assessment (QMRA) techniques, the
      animal model data may provide insights on human dose-response for LD. This
      article focuses on the rationale for selection of the guinea pig model,
      comparison of the dose-response model results, comparison of projected low-dose
      responses for guinea pigs, and risk estimates for humans. Based on both in vivo
      and in vitro comparisons, the guinea pig (Cavia porcellus) dose-response data
      were selected for modeling human risk. We completed dose-response modeling for
      the beta-Poisson (approximate and exact), exponential, probit, logistic, and
      Weibull models for Lp inhalation, mortality, and infection (end point elevated
      body temperature) in guinea pigs. For mechanistic reasons, including low-dose
      exposure probability, further work on human risk estimates for LD employed the
      exponential and beta-Poisson models. With an exposure of 10 colony-forming units
      (CFU) (retained dose), the QMRA model predicted a mild infection risk of 0.4 (as
      evaluated by seroprevalence) and a clinical severity LD case (e.g.,
      hospitalization and supportive care) risk of 0.0009. The calculated rates based
      on estimated human exposures for outbreaks used for the QMRA model validation are
      within an order of magnitude of the reported LD rates. These validation results
      suggest the LD QMRA animal model selection, dose-response modeling, and extension
      to human risk projections were appropriate.

PMID- 18093053
TI  - Consumer evaluations of food risk management quality in Europe.
AB  - In developing and implementing appropriate food risk management strategies, it is
      important to understand how consumers evaluate the quality of food risk
      management practices. The aim of this study is to model the underlying
      psychological factors influencing consumer evaluations of food risk management
      quality using structural equation modeling techniques (SEM), and to examine the
      extent to which the influence of these factors is country-specific (comparing
      respondents from Denmark, Germany, Greece, Slovenia, and the United Kingdom). A
      survey was developed to model the factors that drive consumer evaluations of food
      risk management practices and their relative importance (n= 2,533 total
      respondents). The measurement scales included in the structural model were
      configurally and metrically invariant across countries. Results show that some
      factors appear to drive perceptions of effective food risk management in all the
      countries studied, such as proactive consumer protection, which was positively
      related to consumers' evaluation of food risk management quality, while opaque
      and reactive risk management was negatively related to perceived food risk
      management quality. Other factors appeared to apply only in certain countries.
      For example, skepticism in risk assessment and communication practices was
      negatively related to food risk management quality, particularly so in the UK.
      Expertise of food risk managers appeared to be a key factor in consumers'
      evaluation of food risk management quality in some countries. However, trust in
      the honesty of food risk managers did not have a significant effect on food risk
      management quality. From the results, policy implications for food risk
      management are discussed and important directions for future research are
      identified.

PMID- 18093051
TI  - Bayesian estimation of pharmacokinetic and pharmacodynamic parameters in a mode
      of-action-based cancer risk assessment for chloroform.
AB  - Chloroform is a carcinogen in rodents and its carcinogenicity is secondary to
      events associated with cytotoxicity and regenerative cell proliferation. In this
      study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model
      that links the processes of chloroform metabolism, reparable cell damage, cell
      death, and regenerative cellular proliferation was developed to support a new
      cancer dose-response assessment for chloroform. Model parameters were estimated
      using Markov Chain Monte Carlo (MCMC) analysis in a two-step approach: (1)
      metabolism parameters for male and female mice and rats were estimated against
      available closed chamber gas uptake data; and (2) PD parameters for each of the
      four rodent groups were estimated from hepatic and renal labeling index data
      following inhalation exposures. Subsequently, the resulting rodent PD parameters
      together with literature values for human age-dependent physiological and
      metabolism parameters were used to scale up the rodent model to a human model.
      The human model was used to predict exposure conditions under which chloroform
      mediated cytolethality is expected to occur in liver and kidney of adults and
      children. Using the human model, inhalation Reference Concentrations (RfCs) and
      oral Reference Doses (RfDs) were derived using an uncertainty factor of 10. Based
      on liver and kidney dose metrics, the respective RfCs were 0.9 and 0.09 ppm; and
      the respective RfDs were 0.4 and 3 mg/kg/day.

PMID- 18093055
TI  - Changing forest disturbance regimes and risk perceptions in Homer, Alaska.
AB  - Forest disturbances caused by insects can lead to other disturbances, risks, and
      changes across landscapes. Evaluating the human dimensions of such disturbances
      furthers understanding of integrated changes in natural and social systems. This
      article examines the effects of changing forest disturbance regimes on local risk
      perceptions and attitudes in Homer, Alaska. Homer experienced a spruce bark
      beetle (Dendroctonus rufipennis) outbreak with large-scale tree mortality and a
      5,000-acre fire in 2005. Qualitative interviews and quantitative analysis of mail
      surveys are used to examine community risk perception and relationships with land
      managers pre- and post-fire. Results show a decrease in the saliency of the
      spruce bark beetle as a community issue, a coalescence of community risk
      perceptions about fire, and conflicting findings about satisfaction with land
      managers and its relationship with risk perception.

PMID- 18093056
TI  - Engaging expert peers in the development of risk assessments.
AB  - The participation of external technical experts in the development of risk
      assessment documents and methodologies has expanded and evolved in recent years.
      Many government agencies and authoritative organizations have experts peer review
      important works to evaluate the scientific and technical defensibility and judge
      the strength of the assumptions and conclusions (OMB, 2004; IPCS, 2005; IARC,
      2006; Health Canada, 2007; U.S. EPA, 2006). Expert advice has been solicited in
      other forms of peer involvement, including peer consultation in, for example, the
      U.S. EPA's Voluntary Children's Chemical Evaluation Program (VCCEP). This article
      discusses how the principles and practices of peer review can be extended to
      other types of peer involvement activities (i.e., peer input and peer
      consultation) to develop high-quality risk assessment work products. A
      comprehensive process for incorporating peer input, peer consultation, and peer
      review into risk assessment science is outlined. Four key principles for peer
      involvement-independence, inclusion of appropriate experts, transparency, and a
      robust scientific process-are discussed. Recent examples of peer involvement in
      the development of Health Canada's Priority Substances and Domestic Substance
      List (DSL) programs under the Canadian Environmental Protection Act (CEPA) serve
      to highlight the concepts.

PMID- 18093057
TI  - The risk screening for indoor air pollution chemicals in Japan.
AB  - In recent years, public health problems caused by indoor air pollution have been
      drawing strong public concern in Japan. After conducting extensive exposure
      assessment, governmental agencies have taken effective measures to solve the
      problem; for instance, "Guidelines for indoor air quality (IAQ)" of 13 chemicals,
      for example, formaldehyde, toluene, and xylene, has been established. Thousands
      of chemicals have been identified in the indoor environment. Priority rating of
      those chemicals, however, was not based on the health risk level. We developed a
      risk-screening scheme for indoor air pollution chemicals and analyzed the current
      status of the risk levels of those chemicals in Japan. We researched scientific
      knowledge of health hazards and exposure surveys of indoor air pollution
      chemicals in Japan, and classified those chemicals based on the health risk level
      estimated from the scheme. The risk levels of 93 chemicals were characterized and
      six chemicals (formaldehyde, acrolein, 1,4-dichlorobenzene, benzene,
      tetrachloroethylene, and benzo(a)pyrene) were classified in the highest risk
      category.

PMID- 18093060
TI  - Assessment of histomorphological features of the sternal end of the fourth rib
      for age estimation in Koreans.
AB  - The aim of this study was to assess the histomorphological features of the fourth
      rib and to develop age-predicting equations for Koreans. Sixty-four rib samples
      (36 males and 28 females) obtained from forensic cases were used for developing
      equations. Two thin sections (<100-microm thick) per sample were prepared by
      manual grinding. Multivariate analysis of covariance revealed statistically
      significant differences in age-adjusted histomorphological variables between
      sexes. Using stepwise regression analysis, osteon population density and average
      osteon area were correlated with unknown sex (r2 = 0.826), and sex plus two
      histomorphological variables provided the best results for an age-predicting
      equation given the assumption of knowing the sex of a specimen (r2 = 0.839).
      Average Haversian canal area had little influence on age estimation for male or
      female samples, and relative cortical area was not significantly related to age
      for any specimen.

PMID- 18093061
TI  - Developmental validation of reduced-size STR Miniplex primer sets.
AB  - This paper describes a developmental validation study of three Miniplex sets
      covering 12 of the 13 CODIS loci. As these new sets will be used for the analysis
      of degraded and low level DNA, the validation studies were performed using 100
      125 pg of DNA, the lowest input level at which peak balance, peak intensity, and
      allele consistency were stable. To demonstrate the applicability of the Miniplex
      sets to forensic casework, these validation studies were completed in accordance
      with the Scientific Working Group on DNA Analysis Methods (SWGDAM). A range of
      tests were performed including studies of concordance with standard multiplex
      kits, sensitivity and reproducibility, and PCR amplification conditions.
      Additionally, studies of mixtures, nonhuman and environmentally degraded DNA, and
      simulated forensic samples were performed. Our results demonstrate that Miniplex
      STR amplification procedures are a robust and sensitive tool for the analysis of
      degraded DNA.

PMID- 18093062
TI  - The fate of the chemical warfare agent during DNA extraction.
AB  - Forensic laboratories do not have the infrastructure to process or store
      contaminated DNA samples that have been recovered from a crime scene contaminated
      with chemical or biological warfare agents. Previous research has shown that DNA
      profiles can be recovered from blood exposed to several chemical warfare agents
      after the agent has been removed. The fate of four toxic agents, sulfur mustard,
      sodium 2-fluoroacetate, sarin, and diazinon, in a lysis buffer used in Promega
      DNA IQ extraction protocol was studied to determine if extraction would render
      the samples safe. Two independent analytical methods were used per agent,
      selected from GC-MS, 1H NMR, 19F NMR, (31)P NMR, or LC-ES MS. The methods were
      validated before use. Determinations were carried out in a semi-quantitative way,
      by direct comparison to standards. Agent levels in the elution buffer were found
      to be below the detectable limits for mustard, sarin, sodium 2-fluoroacetate or
      low (<0.02 mg/mL) for diazinon. Therefore, once extracted these DNA samples could
      be safely processed in a forensic laboratory.

PMID- 18093063
TI  - Accumulation of explosives in hair--part II: factors affecting sorption.
AB  - This study examines the sorption of eight explosives (2,4,6-trinitrotoluene
      [TNT]; pentaerythritol tetranitrate [PETN]; hexahydro-1,3,5-trinitro-s-triazine
      [RDX]; diacetone diperoxide [DADP]; triacetone triperoxide [TATP]; ethylene
      glycol [EGDN], nitroglycerin [NG]; and 2,4-dinitrotoluene [DNT]) to human hair.
      The study uses only cut hair, which is exposed to explosive vapor. The vapor
      transfer studies reported herein indicated that hair did not reach saturation
      even after 2.5 years of exposure to TNT. While previous studies showed black hair
      sorbed more explosive than blond or brown, this study reports that red hair
      sorption is similar to black, while grey hairs, exposed along with black hair
      from the same individual, sorbed significantly less explosive than the same
      individual's black hairs. In a study using only black hair, a slight racial bias
      was observed with sorption greater for Mongoloid hair as compared to Caucasian or
      Negroid. Only for Mongoloid hairs were enough samples studied to examine for a
      gender bias, but one was not observed. There was much variability in results in
      all categories (hair color, race, and gender) that trends were established only
      in general terms. Hair at different ages was tested for a few individuals.
      Detailed studies focused on the sorption of TATP and TNT as these appear to be
      sorbed most differently-TATP mainly on the hair surface and TNT both on the
      surface and in the cortex. The uptake of high vapor pressure explosives (e.g.,
      TATP) and moderate vapor pressure explosives (e.g., TNT) by hair was rapid and
      could be detected within about 1 h of exposure. Both explosives were readily
      sorbed by pure melanin.

PMID- 18093064
TI  - Denture marking--patient preference of various methods.
AB  - Dental forensic organizations world wide have recommended that dental prostheses
      should be labeled with at least the patient's (wearer's) name and preferably with
      further unique identifiers such as social security number. A range of methods are
      available and the purpose of this study was to determine, via the means of a
      visual questionnaire, which are the most preferable to those patients who wear
      complete dentures. One hundred edentulous patients attending the Manchester
      Dental Hospital were shown a range of denture labeling methods and asked to rank
      these according to their preference. The most preferred method was that of an
      embedded radio frequency identification microchip (38% rated this as first) and
      the second was an inclusion technique using onion paper (24% rated this as
      first). The least preferred method was the use of a groove cut into the denture
      flange with 71% of patients rating this as the poorest in terms of esthetics. The
      study demonstrates that the method of denture labeling is important to patients
      and to ensure that denture labeling is performed routinely esthetic preferences
      must be considered.

PMID- 18093065
TI  - Aging blow fly eggs using gene expression: a feasibility study.
AB  - Forensic entomology can aid death investigations by using predictable
      developmental changes to estimate the ages of flies associated with a body. In
      developmental stages that do not increase in size however, including the egg and
      pupa, it can be difficult to objectively refine an age estimate beyond the limits
      of the stage duration. Gene transcript levels, changing throughout development,
      represent a potential data source useful for objectively identify smaller units
      of developmental time. The expression of three genes (bcd, sll, cs) was profiled
      throughout the maturation of blow fly eggs to determine the feasibility of
      predicting age, identifying significant linear trends in expression during their
      development. Models estimating egg age made predictions within 2 h of true age
      when all expression data were available, while the presence/absence of cs
      transcripts identified two age classes, together indicating that gene expression
      can be used to more precisely predict blow fly age.

PMID- 18093066
TI  - Collembola of the grave: a cold case history involving arthropods 28 years after
      death.
AB  - This report describes a cold case in which a cadaver of a 28-year-old female was
      exhumed in February 2005 from a cemetery in Battle Creek, Michigan. She had
      sustained a gunshot wound to the head and was found dead in her home on November
      15, 1977. The body of the victim was subsequently embalmed and then buried at a
      depth of 1.8 m in an unsealed casket that was placed inside an unsealed cement
      vault. The exhumation yielded thousands of live specimens of a single species of
      the order Collembola or spring tails, Sinella (Coecobrya) tenebricosa
      (Entomobryidae). This species is considered to be a "tramp" species, cosmopolitan
      in the United States and Canada. Due to the ideal environmental conditions at the
      site, the population of this species underwent growth and development inside the
      casket for a number of years. Collected with the Collembola were large numbers of
      Acarina (mites) of the Family Glycyphagidae, and fly puparia, Conicera tibialis
      Schmitz (Order: Diptera, Family: Phoridae), also known as coffin flies. These
      invertebrates are sometimes mentioned by forensic investigators as occurring on
      corpses in graves, but aspects of their life history are rarely described. The
      species of Collembola that was found surviving and reproducing on this corpse in
      a casket exhumed after 28 years was the oldest reported grave site occurrence for
      any collembolan species based on a survey of the literature back to 1898.

PMID- 18093067
TI  - A comparison of criminal sexual conduct defendants based on victim age.
AB  - This study compared defendants charged with Criminal Sexual Conduct whose victims
      were <6 years of age with defendants whose victims were 12 or more years of age.
      The study included 163 men referred to the evaluation unit of a state center for
      forensic psychiatry. Thirty-eight men had younger victims (YVs) and 125 men had
      older victims (OVs). The variables of comparison were defendant demographic and
      psychiatric variables frequently identified in the sex offender literature.
      Controlling for other demographic and psychiatric variables by use of logistic
      regression modeling, elderly defendants (60 years or greater), and incest
      offenders were three times more likely to have YVs (Odds Ratio [OR] 3.08 and
      3.11, respectively). Unlike previous studies defendants with serious psychiatric
      pathology (psychosis or mania) were no more likely to have YVs (OR 0.66) than
      were defendants without psychosis.

PMID- 18093068
TI  - Methadone toxicity fatalities: a review of medical examiner cases in a large
      metropolitan area.
AB  - Over the past several years, Medical Examiners in Kentucky and around the nation
      have observed a dramatic rise in drug intoxication deaths involving the
      prescription medication methadone. This documented rise in methadone-related
      deaths requires a better understanding of methadone's pathophysiology and the
      ways it contributes to significantly increase morbidity and mortality. This study
      reviews 176 fatalities ascribed to methadone toxicity by the Office of the Chief
      Medical Examiner in Kentucky between 2000 and 2004. Postmortem toxicological
      analysis recorded a more than 10-fold increase in methadone toxicity fatalities,
      rising from 6 cases in 2000 to 68 cases in 2003. Of the 176 methadone-related
      fatalities, methadone was the only drug detected in postmortem blood and urine
      toxicological analyses in 11 (6.25%) cases. The mean methadone blood
      concentration of all 176 cases was 0.535 mg / L (0.02-4.0). The following
      psychoactive medications were detected: antidepressants (39.8%), benzodiazepines
      (32.4%), and other opioids in addition to methadone (27.8%). Cannabinoids were
      detected in 44 (28.4%) cases and cocaine or metabolite in 34 (21.9%) cases. Of
      the 95 cases with a known history of methadone use, 46 (48.4%) involved
      prescription by private physician. The interpretation of blood methadone
      concentrations alone or combined with other psychoactive drugs requires
      consideration of the subject's potential chronic use of and tolerance to the
      drug. A thorough investigation into the practices of procurement and use/abuse of
      methadone is essential to arrive at the proper designation of the cause of death.

PMID- 18093069
TI  - An estimate of the proportion of drug-facilitation of sexual assault in four U.S.
      localities.
AB  - In recent years, drugs including flunitrazepam, gamma-hydroxybutyrate, ketamine,
      and ethanol, have become popularly associated with drug-facilitated sexual
      assault. Other drugs are also candidates as factors in "drug facilitated sexual
      assault" (DFSA). The true extent of DFSA is not known, and is difficult to
      estimate. We recruited sexual assault complainants at four clinics in different
      parts of the U.S. to anonymously provide urine and hair specimens, and to answer
      questions about suspected drugging, drug use, and the sexual assault incident.
      Urine and hair specimens were tested for 45 drugs, including ethanol, and those
      pharmacologically capable of inducing sedation, amnesia, or impairment of
      judgment. Analytical test results were used to estimate the proportion of
      subjects, and the proportion of all complainants to the clinic in the same time
      period, who were victims of DFSA. Overall, cases of 43% of 144 subjects, and 7%
      of 859 complainants, were characterized as DFSA. Subjects underreported their use
      of drugs. The role of toxicological results and history in characterizing DFSA
      cases is discussed.

PMID- 18093070
TI  - Blood cyanide determination in two cases of fatal intoxication: comparison
      between headspace gas chromatography and a spectrophotometric method.
AB  - Blood samples of two cases were analyzed preliminarily by a classical
      spectrophotometric method (VIS) and by an automated headspace gas chromatographic
      method with nitrogen-phosphorus detector (HS-GC/NPD). In the former, hydrogen
      cyanide (HCN) was quantitatively determined by measuring the absorbance of
      chromophores forming as a result of interaction with chloramine T. In the
      automated HS-GC/NPD method, blood was placed in a headspace vial, internal
      standard (acetonitrile) and acetic acid were then added. This resulted in cyanide
      being liberated as HCN. The spectrophotometric (VIS) and HS-GC/NPD methods were
      validated on postmortem blood samples fortified with potassium cyanide in the
      ranges 0.5-10 and 0.05-5 mug/mL, respectively. Detection limits were 0.2 mug/mL
      for VIS and 0.05 mug/mL for HS-GC/NPD. This work shows that results obtained by
      means of the two procedures were insignificantly different and that they compared
      favorably. They are suitable for rapid diagnosis of cyanide in postmortem cases.

PMID- 18093072
TI  - Nature and occurrences of pesticidal deaths in India (1960-2005) for analytical
      consideration.

PMID- 18093073
TI  - Commentary on: Nichols RG. Defending the scientific foundations of the firearms
      and tool mark identification discipline: responding to recent challenges. J
      Forensic Sci 2007; May;52(3):586-94.

PMID- 18093075
TI  - Commentary on: Keiser JA, Bernal V, Wadell JN, Raju S. The uniqueness of the
      human anterior dentition: a geometric and morphometric analysis. J Forensic Sci
      2007;52:3.

PMID- 18093081
TI  - Allele frequencies of DYS19, DYS385, DYS388, DYS389 (I and II), DYS390, DYS391,
      DYS392, and DYS393 STR loci in a Korean population.

PMID- 18093082
TI  - Serbian population data at the CODIS core STR loci.

PMID- 18093083
TI  - Overweight and obesity in preadolescent children and their parents in Cyprus:
      prevalence and associated socio-demographic factors - the CYKIDS study.
AB  - Obesity status differs by socio-demographic factors, but data for Cyprus are
      scarce. An in-depth understanding of this relationship may be useful in designing
      public health programmes. The objective of the present study is to estimate
      overweight and obesity (OW/OB) prevalence among children and adults in Cyprus and
      identify related socio-demographic variables. National cross-sectional study of
      1140 children (mean age 11 +/- 0.98 years) and their parents (mean age 42.5 +/-
      5.8 years, total n = 1954). Obesity was defined according to the World Health
      Organization classification for adults and according to IOTF (International
      Obesity Task Force) criteria for children. Overweight and obesity prevalence
      among girls was 18.3% and 2.9%, respectively, while in boys, 19.0% and 6.0%.
      Among parents, OW/OB prevalence was, respectively, women, 22.6% and 5.8%; men,
      47.1% and 14.1%. Logistic regression analysis in both children and adults
      revealed that the most important socio-demographic predictors of obesity status
      are factors of built environment. Higher prevalence of OW/OB was observed in
      adults living in a house as opposed to an apartment, in older adults, in younger
      children, and in men, irrespective of age. There is a severe obesity problem in
      the Cypriot population; almost one in two adults and at least one in four
      preadolescent children are overweight or obese. Prevalence of OW/OB was related
      to socio-demographic factors, especially among adults and women.

PMID- 18093084
TI  - Severe combined immunodeficiency: a cohort of 40 patients.
AB  - Severe Combined Immunodeficiency (SCID) consists of a heterogeneous group of
      genetic disorders characterized by an arrest in T lymphocyte development which is
      variably associated with an abnormal differentiation of B and NK cells. In order
      to depict the clinical state of Iranian patients with SCID, records of forty
      patients were reviewed. Patients were classified based on the flow cytometry data
      in two groups of B- and B+. In thirty two families (80%) parents were consanguine
      and in 17 families (50%) there were affected members other than proband. We
      showed that autosomal forms of SCID might be more frequent due to higher rate of
      consanguineous marriages. Alongside several infective complications, complicated
      Bacillus Calmette-Guerin (BCG) vaccination was documented in 18 cases (45%)
      following the routine vaccination at birth. BCG immunization is still a part of
      standard vaccination for newborns in developing countries; whereas in communities
      with a better health condition it could be held for a few months and performed
      for kids whose immune system sounds intact. We discuss where consanguine mating
      is common, a test of screening should be run timely. A complete blood count of
      cord blood could reveal lymphocytopenia at birth; this helps early diagnosis.
      Genetic consultation would help the families with affected members preventing new
      SCID offspring.

PMID- 18093085
TI  - Neutrophil but not eosinophil inflammation is related to the severity of a first
      acute epidemic bronchiolitis in young infants.
AB  - Acute bronchiolitis is the main cause of emergency visits and hospitalizations in
      infants. Recent data suggest that neutrophil- and eosinophil-mediated
      inflammations were part of bronchiolitis pathophysiology. Apart from the defined
      risk factors, few was known on the underlying pathophysiology, which might point
      out the differences observed in the severity of the disease. The aim of this
      study was to assess whether the clinical severity of acute epidemic bronchiolitis
      in young infants might be related to a specific underlying inflammatory process.
      Total and differential cell counts, IL-8, eotaxin, eosinophil cationic protein
      (ECP) and albumin levels were assessed at the time of admission in bronchial
      secretions from 37 infants (median age 17 wk) with acute bronchiolitis. Outcome
      severity variables were: hypoxemia, Silverman score, tachypnea, feeding
      alteration, and duration of hospitalization. Neutrophils predominated, and
      eosinophils were present in 54% of the infants. IL-8 levels strongly correlated
      with ECP and albumin levels. Albumin levels were correlated with ECP and eotaxin
      levels. IL-8 levels were higher in infants with hypoxemia and inversely related
      with SaO(2) levels. IL-8 and albumin levels significantly rose with respiratory
      rate, and Silverman score. IL-8, albumin and ECP levels were significantly higher
      in infants hospitalized >/=7 days. Furthermore, IL-8 levels were correlated with
      the duration of hospitalization. Neither cell counts nor eotaxin levels were
      related to the severity criteria studied. This study suggests that IL-8
      associated airway inflammation significantly contributed to the severity of acute
      epidemic bronchiolitis.

PMID- 18093086
TI  - The profile of renal function over time in a cohort of pediatric heart transplant
      recipients.
AB  - To assess the burden over time of renal dysfunction in pediatric heart transplant
      patients using an objective measure on an annual basis for serial comparison. GFR
      was measured at regular interval by nuclear medicine scintigraphy. Results were
      analyzed in relation to age, time post-transplantation, gender, and average
      calcineurin-inhibitor dose for the first two months post-transplantation. Results
      were compared with cGFR using the Schwartz equation. A total of 91 patients (56
      males) transplanted between 1990 and 2004 underwent 373 GFR measurements. Median
      age at transplantation was 3.3 yr (birth - 17.8). Median first GFR at 0.7 yr (0.1
      4.1) post-transplant was normal (94 mL/kg/1.73 m(2)). Freedom from at least mild
      renal insufficiency was 84% and 33% at one and five years post-transplant.
      Females had better renal function early post-transplant (GFR 105 mL/min/1.73
      m(2)) but an increased probability of an abnormal GFR over time. Higher
      calcineurin inhibitor dose in the first two months post-transplantation was
      associated with an increasing probability of an abnormal GFR over time. The cGFR
      overestimated the measured GFR by 33 +/- 26 mL/kg/1.73 m(2). Renal insufficiency
      is an important morbidity after pediatric transplantation with the majority of
      patients experiencing at least mild renal dysfunction. Calculated GFR
      significantly underestimates the burden of renal insufficiency in this patient
      population.

PMID- 18093087
TI  - The technical pitfalls of duct-to-duct biliary reconstruction in pediatric living
      donor left-lobe liver transplantation: the impact of stent placement.
AB  - The feasibility of D-D biliary reconstruction in pediatric LDLT using a left-lobe
      graft is still controversial. The medical records of 19 pediatric patients (age:
      four months to 16 yr) were reviewed. The biliary reconstruction was performed in
      an end-to-end fashion using absorbable sutures. An external biliary tube was
      placed into the bile duct through the anastomotic site (n = 10) and not through
      the anastomotic site (n = 4). An external tube was not used in five patients. The
      median follow-up was 4.7 yr. Nine patients had 11 biliary complications (leakage,
      n = 2; stricture, n = 7; stricture with leakage, n = 2). Due to biliary
      complications, conversion to an R-Y was required in five patients, and four
      patients required radiological or endoscopic management. The patients younger
      than one yr of age required conversion to R-Y within one wk after LDLT. The
      analysis of factors related to biliary complications revealed that the use of a
      trans-anastomotic biliary tube was the only significant factor to avoid biliary
      complications. In conclusion, D-D biliary reconstruction in LDLT using a left
      lobe graft is feasible in selected cases, though it remains challenging. The use
      of a trans-anastomotic biliary tube is important to avoid biliary complications.

PMID- 18093088
TI  - Post-transplant diabetes mellitus in children following renal transplantation.
AB  - PTDM plays a role in chronic allograft nephropathy and decreases graft and
      patient survival. Considering the serious outcome of chronic hyperglycemia, the
      importance of early recognition and the few data in children, in this
      retrospective analysis we studied the characteristics and risk factors of PTDM in
      45 pediatric renal transplant recipients receiving Tac or CyA-based
      immunosuppression. Fasting blood sampling and OGTT were performed. PTDM has been
      developed in six patients (13%), while seven children (16%) had IGT, with the
      overall incidence of a glucose metabolic disorder of 29% in pediatric renal
      transplants. Patients in the PTDM + IGT group were younger and had higher
      systolic blood pressure and serum triglyceride level than children with normal
      glucose tolerance. Multivariate analysis identified Tac treatment, Tac trough
      level, steroid pulse therapy and family history of diabetes to be associated with
      the onset of PTDM. In pediatric renal transplants, OGTT and frequent assessment
      of blood glucose levels might be essential not only in the post-transplant
      management, but also prior to transplantation, particularly with family history
      of diabetes. Careful monitoring and modified protocols help to minimize the side
      effects of Tac and corticosteroids.

PMID- 18093089
TI  - Transferred NOE and saturation transfer difference NMR studies of novobiocin
      binding to EnvZ suggest binding mode similar to DNA gyrase.
AB  - Histidine protein kinases (HPKs) are a class of receptor proteins found in
      bacterial two-component signal transduction systems, which allow bacteria to
      respond to changes in their external environment. To date, there are few potent
      inhibitors of histidine kinases, despite their potential ability to weaken
      bacteria against antibiotic treatment. EnvZ is a histidine protein kinase with
      osmoregulatory function in bacteria with sequence and topological similarity to
      DNA Gyrase B. DNA Gyrase B has several well-characterized potent inhibitors,
      including novobiocin and clorobiocin which have detailed structures in complex.
      With fluorescence competition experiments, we have determined that novobiocin
      binds to EnvZ with a (novo)K(D) 120 +/- 20 microm. NMR transferred NOE (trNOE)
      experiments, and saturation transfer difference (STD) experiments suggest that
      novobiocin binds to EnvZ in a conformation and orientation similar to its binding
      with DNA Gyrase B. These experiments suggest some similarity in the pocket
      despite weaker affinity for EnvZ by novobiocin.

PMID- 18093091
TI  - The Scl1 protein of M6-type group A Streptococcus binds the human complement
      regulatory protein, factor H, and inhibits the alternative pathway of complement.
AB  - Non-specific activation of the complement system is regulated by the plasma
      glycoprotein factor H (FH). Bacteria can avoid complement-mediated opsonization
      and phagocytosis through acquiring FH to the cell surface. Here, we characterize
      an interaction between the streptococcal collagen-like protein Scl1.6 of M6-type
      group A Streptococcus (GAS) and FH. Using affinity chromatography with
      immobilized recombinant Scl1.6 protein, we co-eluted human plasma proteins with
      molecular weight of 155 kDa, 43 kDa and 38 kDa. Mass spectrometry identified the
      155 kDa band as FH and two other bands as isoforms of the FH-related protein-1.
      The identities of all three bands were confirmed by Western immunoblotting with
      specific antibodies. Structure-function relation studies determined that the
      globular domain of the Scl1.6 variant specifically binds FH while fused to
      collagenous tails of various lengths. This binding is not restricted to Scl1.6 as
      the phylogenetically linked Scl1.55 variant also binds FH. Functional analyses
      demonstrated the cofactor activity of the rScl1.6-bound FH for factor I-mediated
      cleavage of C3b. Finally, purified FH bound to the Scl1.6 protein present in the
      cell wall material obtained from M6-type GAS. In conclusion, we have identified a
      functional interaction between Scl1 and plasma FH, which may contribute to GAS
      evasion of complement-mediated opsonization and phagocytosis.

PMID- 18093090
TI  - An atypical orthologue of 6-pyruvoyltetrahydropterin synthase can provide the
      missing link in the folate biosynthesis pathway of malaria parasites.
AB  - Folate metabolism in malaria parasites is a long-standing, clinical target for
      chemotherapy and prophylaxis. However, despite determination of the complete
      genome sequence of the lethal species Plasmodium falciparum, the pathway of de
      novo folate biosynthesis remains incomplete, as no candidate gene for
      dihydroneopterin aldolase (DHNA) could be identified. This enzyme catalyses the
      third step in the well-characterized pathway of plants, bacteria, and those
      eukaryotic microorganisms capable of synthesizing their own folate. Utilizing
      bioinformatics searches based on both primary and higher protein structures,
      together with biochemical assays, we demonstrate that P. falciparum cell extracts
      lack detectable DHNA activity, but that the parasite possesses an unusual
      orthologue of 6-pyruvoyltetrahydropterin synthase (PTPS), which simultaneously
      gives rise to two products in comparable amounts, the predominant of which is 6
      hydroxymethyl-7,8-dihydropterin, the substrate for the fourth step in folate
      biosynthesis (catalysed by 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase;
      PPPK). This can provide a bypass for the missing DHNA activity and thus a means
      of completing the biosynthetic pathway from GTP to dihydrofolate. Supported by
      site-directed mutagenesis experiments, we ascribe the novel catalytic activity of
      the malarial PTPS to a Cys to Glu change at its active site relative to all
      previously characterized PTPS molecules, including that of the human host.

PMID- 18093092
TI  - The antibacterial activity of peptides derived from human beta-2 glycoprotein I
      is inhibited by protein H and M1 protein from Streptococcus pyogenes.
AB  - During the last years, the importance of antibacterial peptides has attracted
      considerable attention. We report here that peptides derived from the fifth
      domain of beta-2 glycoprotein I (beta(2)GPI), a human heparin binding plasma
      protein, have antibacterial activities against Gram-positive and Gram-negative
      bacteria. Streptococcus pyogenes, an important human pathogen that can survive
      and grow in human blood, has developed mechanisms to escape the attack by these
      peptides. Thus, protein H and M1 protein, two surface proteins of the highly
      pathogenic S. pyogenes AP1 strain, bind full-length beta(2)GPI and thereby
      prevent the processing of beta(2)GPI by proteases from polymorphonuclear
      neutrophils (PMNs) into antibacterial peptides. In addition, protein H and M1
      protein, released from the bacterial cell wall by PMN-derived proteases, bind to,
      and inhibit the activity of, beta(2)GPI-derived antibacterial peptides. Taken
      together, the data suggest that the interaction between the streptococcal
      proteins and beta(2)GPI or beta(2)GPI-derived peptides presents a novel mechanism
      to resist an antibacterial attack by beta(2)GPI-cleavage products.

PMID- 18093093
TI  - Single amino acid substitutions in either YhjD or MsbA confer viability to 3
      deoxy-d-manno-oct-2-ulosonic acid-depleted Escherichia coli.
AB  - The Escherichia coli K-12 strain KPM22, defective in synthesis of 3-deoxy-d-manno
      oct-2-ulosonic acid (Kdo), is viable with an outer membrane (OM) composed
      predominantly of lipid IV(A), a precursor of lipopolysaccharide (LPS)
      biosynthesis that lacks any glycosylation. To sustain viability, the presence of
      a second-site suppressor was proposed for transport of lipid IV(A) from the inner
      membrane (IM), thus relieving toxic side-effects of lipid IV(A) accumulation and
      providing sufficient amounts of LPS precursors to support OM biogenesis. We now
      report the identification of an arginine to cysteine substitution at position 134
      of the conserved IM protein YhjD in KPM22 that acts as a compensatory suppressor
      mutation of the lethal DeltaKdo phenotype. Further, the yhjD400 suppressor allele
      renders the LPS transporter MsbA dispensable for lipid IV(A) transmembrane
      trafficking. The independent derivation of a series of non-conditional KPM22-like
      mutants from the Kdo-dependent parent strain TCM15 revealed a second class of
      suppressor mutations localized to MsbA. Proline to serine substitutions at either
      residue 18 or 50 of MsbA relieved the Kdo growth dependence observed in the
      isogenic wild-type strain. The possible impact of these suppressor mutations on
      structure and function are discussed by means of a computationally derived
      threading model of MsbA.

PMID- 18093094
TI  - Sexual dysfunction in men who abuse illicit drugs: a preliminary report.
AB  - INTRODUCTION: Despite being seen as aphrodisiacs, illicit drugs are reported to
      have detrimental effects on male sexual function but most studies have been based
      on small case numbers with ambiguous results. AIMS: To assess the impact of
      illicit drugs abuse on male sexual function. MAIN OUTCOME MEASURES: International
      Index of Erectile Function (IIEF) and global assessment questions. METHODS:
      Illicit drug abusers in a Drug Abstention and Treatment Center were recruited to
      complete the questionnaires and their data were compared with an age-matched
      control. RESULTS: The abusers (N = 701, mean age 33.8 years) had a lower mean
      IIEF score in each domain than that of the controls (N = 196, mean age 35.4
      years). Heroin, amphetamine, and MDMA ("Ecstasy") were the leading drugs used.
      Erectile dysfunction (ED) was reported in 36.4% of the abusers and the odds ratio
      of having ED (compared with the controls) in mono-users of heroin, amphetamine,
      and MDMA was 4.8 (P < 0.05), 3.2 (P < 0.05), and 1.4 (P > 0.05), respectively. Of
      the abusers, 38.6% reported to have decreased sexual desire with illicit drug
      use, more often seen in the heroin mono-users (46.7%), and 18.4% reported to have
      enhanced sexual desire, more often seen in the amphetamine mono-users (22.6%).
      Mean IIEF sexual desire domain score of the abusers was lower than that of the
      control, even for those who reported to have enhanced sexual desire. Increased
      and decreased ejaculation latency affected by illicit drugs was reported in 49.9
      and 14.3%, respectively, of the abusers, showing no significant difference among
      the mono-users of three different drugs. CONCLUSIONS: Illicit drug male abusers
      were prone to have ED, decreased sexual desire, and increased ejaculation
      latency. ED and decreased sexual desire were most commonly seen in heroin,
      followed by amphetamine and MDMA mono-users, while increased ejaculation latency
      occurred commonly in all of the abusers.

PMID- 18093095
TI  - Premenopausal women with sexual dysfunction: the need for a bladder function
      history.
AB  - INTRODUCTION: Despite the high prevalence of both female sexual problems and
      bladder dysfunction in the premenopausal population, sexual history forms used in
      primary care offices rarely include questions about the impact of bladder
      dysfunction on sexual health. AIM: To provide a review of the literature that
      illustrates the relationship between bladder problems and sexual performance of
      premenopausal women. MAIN OUTCOME MEASURES: To objectively support by a review of
      the literature the need for a complete bladder history in when evaluating
      premenopausal women with female sexual dysfunction. METHODS: Pubmed was searched
      for all articles (from November 1980 to June 2007) that reported on the effect
      bladder dysfunction has on premenopausal female sexual function. RESULTS: The
      scant literature available strongly suggested that bladder dysfunction is a
      contributor to sexual dysfunction and that this medical concern should be
      considered in all women, regardless of age who present with sexual complaints.
      CONCLUSION: Further studies need to be conducted in order to solidify a direct
      causal relationship between bladder dysfunction and premenopausal female
      sexuality. These studies should include a larger sample size, clearly defined
      types of sexual dysfunction and bladder dysfunction, and appropriate follow-up of
      patient responses using validated objective and subjective outcome modalities to
      confirm that the patient responses are factual.

PMID- 18093096
TI  - Erectile dysfunction in men receiving methadone and buprenorphine maintenance
      treatment.
AB  - INTRODUCTION: Use of opiates/opioids is associated with hypoactive sexual desire,
      erectile and orgasmic dysfunction. AIM: To determine prevalence and investigate
      etiology of sexual dysfunction in men on methadone or buprenorphine maintenance
      treatment (MMT, BMT). MAIN OUTCOME MEASURES: International Index of Erectile
      Function (IIEF), hormone assays, Beck Depression Inventory. METHODS: A total of
      103 men (mean age 37.6 +/- 7.9) on MMT (N = 84) or BMT (N = 19) were evaluated
      using the IIEF, hormone assays, Beck Depression Inventory, body mass index (BMI),
      demographic, and other substance use measures. RESULTS: Mean total IIEF scores
      for partnered men were lower for MMT (50.4 +/- 18.2; N = 53) than reference
      groups (61.4 +/- 16.8; N = 415; P < 0.0001) or BMT (61.4 +/- 7.0; N = 14; P =
      0.048). Among partnered men on MMT, 53% had erectile dysfunction (ED) compared
      with 24% of reference groups; 26% had moderate to severe ED, 12.1% in under 40s
      and 40.0% among those 40+ years. On multiple regression, depression, older age,
      and lower total testosterone were associated with lower IIEF and EF domain; on
      multivariate analysis, there were no significant associations between IIEF or EF
      and free testosterone, opioid dose, cannabis or other substance use, viral
      hepatitis, or BMI. Total testosterone accounted for 16% of IIEF and 15% of EF
      variance. Men without sexual partners had lower Desire and Erection Confidence
      scores and less recent sexual activity, suggesting potentially higher prevalence
      of sexual dysfunction in this group. CONCLUSION: Men on MMT, but not BMT, have
      high prevalence of ED, related to hypogonadism and depression. Practitioners
      should screen for sexual dysfunction in men receiving opioid replacement
      treatment. Future studies of sexual dysfunction in opioid-treated men should
      examine the potential benefits of dose reduction, androgen replacement, treatment
      of depression, and choice of opioid.

PMID- 18093097
TI  - Profile of serum testosterone levels after application of testosterone ointment
      (glowmin) and its clinical efficacy in late-onset hypogonadism patients.
AB  - INTRODUCTION: Testosterone replacement therapy has been applied to alleviate the
      various symptoms of late-onset hypogonadism (LOH) patients. Several routes are
      available for the administration of testosterone to LOH patients, and transdermal
      delivery is an attractive method above all. AIM: The aim of this article was to
      clarify the profile of serum total testosterone (TT) and free testosterone (FT)
      levels after application of testosterone ointment (Glowmin [GL], Daito
      Pharmaceutical Co. Ltd., Tokyo, Japan) and its clinical efficacy in LOH patients.
      METHODS: Serum TT and FT levels were examined in healthy male volunteers and LOH
      patients after application of 3 mg of GL. Then, 50 LOH patients received 3 mg of
      GL twice daily on scrotal skin (6 mg/day) for 12 weeks. Subsequently, TT and FT
      levels immediately prior to GL application were compared with those at 1 hour
      after GL treatment. Furthermore, the clinical effects of GL in the aforementioned
      50 LOH patients were estimated after 12 weeks of GL treatment. MAIN OUTCOME
      MEASURES: Hormonal effects of GL were evaluated by serum TT and FT levels. Aging
      males symptoms (AMS), international index of erectile function (IIEF-5), and MOS
      36-item short form Healthy Survey (SF-36) questionnaire were used to assess the
      clinical efficacy of GL for LOH patients. RESULTS: Maximum TT and FT values,
      which were detected 1-2 hours after application of a 2-cm line of GL (3 mg of
      testosterone) to scrotal skin, were not elevated beyond physiological levels;
      subsequently, these levels returned to circadian rhythm after 4 hours in four
      healthy male volunteers. The highest TT and FT levels were also obtained after 1
      2 hours in four LOH patients involving identical administration methods;
      moreover, these levels were maintained within a normal range for 6 hours. After
      12 weeks of GL treatment in 50 LOH patients, TT and FT levels demonstrated the
      same satisfactory response as that of the initial GL administration without GL
      accumulation effects. GL accumulation after 1 week in healthy men and after 12
      weeks in LOH patients was not observed. Furthermore, AMS score decreased
      markedly; IIEF-5 and four domains of the SF-36 score were elevated significantly
      following GL application. Severe adverse reactions were not observed.
      CONCLUSIONS: Accordingly, GL, which is a short-acting testosterone ointment
      eliciting physiological elevation of TT and FT, appears to be suitable for LOH
      treatment.

PMID- 18093098
TI  - Dilatation and stenting of the fontan pathway: impact of the stenosis treatment
      on chronic ascites.
AB  - OBJECTIVE: Low pulmonary artery pressure (PAP) and unobstructed flow in the
      pulmonary arteries (PA) and the systemic veins are the most important factors for
      optimal long-term Fontan hemodynamics. We retrospectively analyzed the impact of
      transcatheter interventions for treatment of stenoses in the Fontan pathway to
      optimize the circulation, with special attention to chronic ascites. PATIENTS AND
      DESIGN: Sixty-three of a total of 112 patients underwent heart catheterization
      4.6 (1.0-11.4) years after Fontan operation. The median age of the patients at
      the end of follow-up was 11 (3.1-45) years. Patients were divided into two
      groups, one with chronic ascites and one without. The impact of elevated PAP and
      of morphologic stenoses in the Fontan pathway for the development of chronic
      ascites was analyzed. RESULTS: Ascites was observed in 11 patients; 5 of them had
      stenosis in the Fontan pathway (P = 0.010). High PAP of 15 mmHg or more (n = 13)
      was correlated positively with the development of ascites (5 of 13, P = 0.040).
      Twenty interventions for removal of stenosis in the Fontan pathway were performed
      in 14 patients. We observed temporary relief of ascites in all and complete
      resolution of ascites after alleviation of the stenosis in 2 patients with PAP
      <12 mmHg. CONCLUSION: Transcatheter treatment of stenosis can effectively improve
      the hemodynamics in Fontan circulation, even in patients without measurable
      pressure gradient. In those with low PAP, it may lead to the disappearance of
      chronic ascites.

PMID- 18093099
TI  - Migraine headache relief after percutaneous transcatheter closure of interatrial
      communications.
AB  - BACKGROUND: Migraine headache (MHA) is present in 12% of adults, but has been
      reported to have a higher prevalence in patients with presumed paradoxical
      embolism and patent foramen ovale. PFO closure in these patients has been
      reported to improve migraine, but follow-up periods in previous studies have been
      relatively short and concomitant medical therapy as well as placebo effects might
      have influenced the results. This study investigated the long term course of MHA
      in a large cohort of patients after closure of PFO well beyond the initial phase
      of concomitant antiplatelet medication. METHODS: 191 consecutive patients with
      presumed paradoxical embolism underwent percutaneous transcatheter closure of
      patent interatrial communications for prevention of recurrent thromboembolism. We
      report the course of MHA before and after closure. RESULTS: Before the procedure,
      MHA was present in 24% of patients. At a mean follow-up of 38 months (range 6 to
      82) after the procedure MHA had disappeared completely in 24% of patients, and in
      another 63% symptoms had improved. At a mean duration of follow-up of 38 months a
      significant reduction (p < 0.000) of number, intensity, duration of episodes, and
      in the number of accompanying symptoms during an MHA episode was found.
      CONCLUSIONS: Percutaneous transcatheter closure of patent interatrial
      communications results in significant amelioration of MHA in 87% of patients
      (complete resolution in 24% and significant improvement in symptoms in 63%).
      Ongoing randomized trials and larger epidemiologic surveys need to further
      elucidate the role of device therapy for MHA.

PMID- 18093100
TI  - A randomized trial of 5 versus 7 French guiding catheters for transfemoral
      percutaneous coronary stent implantation.
AB  - Comparative studies between 5 French guiding catheter and others of larger size
      using the transfemoral approach to coronary stenting have not been described.
      Coronary stent implantation was performed in 90 patients in a randomized trial.
      The primary end-point was to compare the incidence of successful uncomplicated
      stent implantation per lesion with the 5F and 7F guiding catheters. Patients were
      excluded for excessive vessel tortuosity or anticipated need for equipment not
      fitting through a 5 catheter. Baseline characteristics and the use of direct
      stenting did not differ between the two groups. The primary success rate was
      97.8% per patient in both groups and 98% per lesion in the 5 French and 97.9% in
      the 7 French. Guiding catheter change was necessary in 1 patient in each group to
      successfully complete the procedure in both groups. The amount of contrast used
      was 63 +/- 27.3 mL in the 5 French and 76 +/- 25 mL in the 7 French groups (P <
      0.05). Vascular complications and blood transfusions occurred somewhat more
      frequently in the 7 French group (P = 0.058). The manual compression time after
      sheath removal was 5.1 +/- 2.0 min and 8.0 +/- 4.3 min, respectively, in the 5
      and 7 French groups (P < 0.01). In conclusion, the 5 French guiding catheters
      showed a similar success rate with coronary stenting when compared to the 7
      French, but the amount of contrast used and manual compression time after sheath
      removal, as well as the rate of vascular and bleeding complications, were reduced
      in the 5 French group.

PMID- 18093102
TI  - Once a week is not enough: evaluating current measures of teamworking in stroke.
AB  - RATIONALE, AIMS AND OBJECTIVES: Stroke care has been at the forefront of the
      drive to deliver health care by teamworking in the UK. Teamworking is the subject
      of ongoing audit of stroke provision with measures such as a weekly team meeting
      being used to evaluate services. A qualitative study was recently undertaken to
      explore these evaluations and to gain further understanding of the processes
      underlying teamworking practice. METHODS: Three case study sites across the
      stroke care pathway were investigated using data collection methods of fieldwork
      observation, interviews and visual imagery. The data were coded and analysed in
      an inductive process in parallel to the data gathering. RESULTS: It was found
      that teamworking practice was affected by organizational conditions, such as
      location of staff, time constraints, management structures and team contact.
      Other important aspects of teamworking related to the formation of subteams,
      decision-making processes, leadership, identification of goals, and training in
      teamworking. CONCLUSIONS: It is suggested that additional measures of team
      functioning are required. This paper highlights the importance of the
      organizational background with the need to consider team size, accountability and
      changing group membership. It discusses the decision-making systems and the need
      to more fully consider the role and purpose of team meetings.

PMID- 18093103
TI  - Response and non-response to postal questionnaire follow-up in a clinical trial-
      a qualitative study of the patient's perspective.
AB  - RATIONALE, AIMS AND OBJECTIVES: Many studies have investigated response issues to
      postal questionnaires in educational and market research surveys. Behavioural
      theories have been applied to survey research to understand response decisions.
      Little attention has focussed specifically on response issues to postal
      questionnaires used to collect data in clinical trials. This qualitative study,
      nested within an acute injury RCT, examines factors affecting response and non
      response from the clinical trial participant's perspective. METHODS: Qualitative
      study comprising of 22 semi-structured interviews with a purposeful sample of
      clinical trial participants. The sample consisted of 14 'responders' and 8 'non
      responders' to postal questionnaire follow-up. Data were analysed using the
      Framework Method. RESULTS: Prevalent reasons for responding to the questionnaires
      were the perceived personal benefit, commitment to the trial and perceived
      obligation to respond. Altruism was also a strong motivator. There was an
      association between the participant's understanding of the trial and their
      likelihood of responding. Most non-responders were happy with the trial and gave
      reasons for non-response such as being 'lazy' and 'forgetful'. Participants who
      considered themselves to be fully recovered were less likely to respond. There
      also emerged a relationship between response and treatment preference.
      CONCLUSIONS: Saliency of the questionnaire topic is one of the most prevalent
      influences on response in clinical trials. This is not evident in the survey
      literature. Improvements in response rates may be gained by ensuring participants
      fully understand the trial procedures and stressing the importance of responding
      even if a full recovery has been made.

PMID- 18093101
TI  - Phenotypic variability and craniofacial dysmorphology: increased shape variance
      in a mouse model for cleft lip.
AB  - Cleft lip and palate (CL/P), as is true of many craniofacial malformations in
      humans, is etiologically complex and highly variable in expression. A/WySn mice
      are an intriguing model for human CL/P because they develop this dysmorphology
      with a variable expression pattern, incomplete penetrance and frequent unilateral
      expression on a homogeneous genetic background. The developmental basis for this
      variation in expression is unknown, but of great significance for understanding
      such expression patterns in humans. As a step towards this goal, this study used
      three-dimensional geometric morphometric and novel high throughput morphometric
      techniques based on three-dimensional computed microtomography of mouse embryos
      to analyze craniofacial shape variation during primary palate formation. Our
      analysis confirmed previous findings based on two-dimensional analyses that the
      midface in A/WySn embryos, and the maxillary prominence in particular, is
      relatively reduced in size and appears to be developmentally delayed. In
      addition, we find that shape variance is increased in A/WySn embryos during
      primary palate formation compared to both C57BL/6J mice and the F1 crosses
      between these strains. If the reduction in midfacial growth caused by the Wnt9b
      hypomorphic mutation pushes A/WySn mice closer on average to the threshold for
      cleft lip formation, the elevated shape variance may explain why some, but not
      all, embryos develop the dysmorphology in a genetically homogeneous inbred line
      of mice.

PMID- 18093104
TI  - The relationships between need profiles, clinical symptoms, functioning and the
      well-being of inpatients with severe mental disorders.
AB  - BACKGROUND: This study aimed to examine the subjective needs and their
      relationship with clinical symptoms, functioning and well-being of hospitalized
      patients with severe mental disorders. METHODS: Using the Camberwell Assessment
      of Need, we surveyed 52 consecutive voluntarily readmitted inpatients aged 18-65
      years fulfilling the ICD-10 criteria for schizophrenia and schizoaffective
      disorders. Current levels of clinical symptoms, functioning and well-being were
      assessed using the Positive and Negative Syndrome Scale, Global Life Functioning
      inventory and the General Health Questionnaire, respectively. Spearman's
      correlation coefficients and t-test comparisons were performed to examine the
      relationships between the parameters of interest. RESULTS: The basic needs of
      inpatients in food and accommodation were met in a greater extent than social
      needs ('sexual expression' and 'intimate relationships') and informational needs
      ('information on condition and treatment'). Patients' unmet needs were associated
      with current symptomatology severity rather than with the course of disorder.
      CONCLUSION: In any course of illness, services must help patients in solution of
      their problem (met their needs) immediately after clinical improvement or
      alleviation of psychiatric symptoms.

PMID- 18093105
TI  - Marital status, feeling depressed and self-rated health in rural female primary
      care patients.
AB  - OBJECTIVE: To determine whether marital status and self-assessed mental health
      are independent risk factors for poor self-rated overall health among female
      primary care patients. DESIGN: We conducted a cross-sectional survey of family
      medicine patients treated in a clinic in rural Minnesota. Complete responses were
      obtained from 723 women. Self-ratings of mental health, demographics and symptoms
      were used to predict self-rated overall health. RESULTS: Women who were single,
      divorced or otherwise not married, or widowed had lower odds of good self-rated
      overall health (OR = 0.39, P = 0.004) compared with married women. Women who were
      65 years of age and over (OR = 0.31, P = 0.017), women who rated themselves as
      depressed (OR = 0.54, P = 0.029), and women who reported more physical symptoms
      (OR = 0.78, P = 0.000) also were less likely to have good health, compared with
      younger women, women who did not feel depressed, and women with fewer physical
      symptoms, respectively. Education was not independently related to health in this
      sample. Worry was related to health in the univariate analysis but not after
      controlling for self-assessed depression. CONCLUSIONS: In order to improve
      overall health among rural women seen in primary care settings, special attention
      may need to be directed at women who are single, are older, report more physical
      symptoms, and feel depressed. Programmes should include self-help materials,
      support groups and counselling services addressing social isolation, employment
      and financial hardship.

PMID- 18093106
TI  - The validity and reliability of the Turkish version of the MacNew Heart Disease
      Questionnaire in patients with angina.
AB  - AIMS AND OBJECTIVES: Health-related quality of life (HRQL) is an important
      patient-reported outcome when identifying the effects of the angina and
      evaluating the efficacy of treatment. The aim of this study was to determine the
      reliability and validity of the Turkish version of the MacNew Heart Disease HRQL
      Questionnaire (MacNew) in patients with angina. METHOD: The Short Form SF-36, the
      MacNew, and the Hospital Anxiety and Depression Scale were completed by the 125
      patients in first 2-3 days after admission to the coronary care unit. Internal
      consistency reliability (Cronbach's alpha) and reproducibility (intraclass
      correlation coefficients, ICC) of the MacNew were assessed, and test-retest
      reproducibility was evaluated over a 2-month period in 25 clinically stable
      patients. RESULTS: The original three-factor structure for the Turkish MacNew was
      confirmed, with construct validity only partially confirmed; reliability
      statistics show that Cronbach's alpha exceeded 0.80 and the ICC exceeded 0.60 for
      all MacNew scales. Discriminative validity of the MacNew was confirmed.
      CONCLUSION: The MacNew appears to be reliable and valid in Turkish patients with
      angina.

PMID- 18093107
TI  - Estimating waste in frontline health care worker activities.

PMID- 18093108
TI  - Impact of quality circles for improvement of asthma care: results of a randomized
      controlled trial.
AB  - RATIONALE AND AIMS: Quality circles (QCs) are well established as a means of
      aiding doctors. New quality improvement strategies include benchmarking
      activities. The aim of this paper was to evaluate the efficacy of QCs for asthma
      care working either with general feedback or with an open benchmark. METHODS:
      Twelve QCs, involving 96 general practitioners, were organized in a randomized
      controlled trial. Six worked with traditional anonymous feedback and six with an
      open benchmark; both had guided discussion from a trained moderator. Forty-three
      primary care practices agreed to give out questionnaires to patients to evaluate
      the efficacy of QCs. RESULTS: A total of 256 patients participated in the survey,
      of whom 185 (72.3%) responded to the follow-up 1 year later. Use of inhaled
      steroids at baseline was high (69%) and self-management low (asthma education
      27%, individual emergency plan 8%, and peak flow meter at home 21%). Guideline
      adherence in drug treatment increased (P = 0.19), and asthma steps improved (P =
      0.02). Delivery of individual emergency plans increased (P = 0.008), and
      unscheduled emergency visits decreased (P = 0.064). There was no change in asthma
      education and peak flow meter usage. High medication guideline adherence was
      associated with reduced emergency visits (OR 0.24; 95% CI 0.07-0.89). Use of
      theophylline was associated with hospitalization (OR 7.1; 95% CI 1.5-34.3) and
      emergency visits (OR 4.9; 95% CI 1.6-14.7). There was no difference between
      traditional and benchmarking QCs. CONCLUSIONS: Quality circles working with
      individualized feedback are effective at improving asthma care. The trial may
      have been underpowered to detect specific benchmarking effects. Further research
      is necessary to evaluate strategies for improving the self-management of asthma
      patients.

PMID- 18093109
TI  - What do you think of your dentist? A dental practice assessment questionnaire.
AB  - Background In order to comply with clinical governance requirements and receive
      payments under the Qualities and Outcomes Framework, GPs are required to
      undertake an annual survey of patient experience using a validated assessment
      tool. Dentists, in contrast, have embryonic clinical governance structures. The
      provision of quality dental services was identified in NHS Dentistry: Options for
      Change as a priority for the future. In anticipation of the PCT role in
      commissioning quality NHS dental care, Croydon PCT has developed an instrument to
      examine various aspects of the patient experience. Methods A review of existing
      literature identified five generic dimensions of patient satisfaction with dental
      care: technical competence, interpersonal factors, convenience, costs and
      facilities. The dental practice assessment questionnaire was developed to cover
      all of these dimensions using a number of validated measures and modified
      questions. A small scale pilot was undertaken before the questionnaire was sent
      to a 10% random stratified sample of the PCT population. Results Validation
      analyses were undertaken in conjunction with the GKT Dental Institute. Cronbach's
      alpha demonstrated very high levels of internal consistency, and factor analysis
      and correlation coefficients demonstrated high levels of factorial and concurrent
      validity respectively. Subgroup analysis revealed differences in reported
      satisfaction by age and ethnic group, and that those who attend because of pain
      or a dental emergency are generally less satisfied with the care they receive.
      These results are consistent with previous research findings. Conclusion The
      dental practice assessment questionnaire is a valid and consistent measurement
      tool. Its use could be extended across the NHS without difficulty.

PMID- 18093110
TI  - A rare tumour of the nail apparatus: onychomatricoma.

PMID- 18093111
TI  - The efficacy of topical 0.2% hyaluronic acid gel on recurrent oral ulcers:
      comparison between recurrent aphthous ulcers and the oral ulcers of Behcet's
      disease.
AB  - BACKGROUND: Hyaluronic acid (HA) is a primary component of the extracellular
      matrix, and the efficacy of HA on oral ulcers is rarely reported. OBJECTIVE: To
      observe the efficacy and safety of the topical application of 0.2% HA gel on
      recurrent oral ulcers and to compare its effects in patients with recurrent
      aphthous ulcers (RAU) and the oral ulcers of Behcet's disease (BD). MATERIALS AND
      METHODS: Thirty-three outpatients with recurrent oral ulcers were included in the
      study (17 patients: BD, 16 patients: RAU). The patients used topical 0.2% HA gel
      twice daily for 2 weeks. The subjective parameters of patients [number of ulcers,
      healing period, visual analogue scale (VAS) for pain] were investigated and
      objective assessments (number of ulcers, maximal area of ulcer and inflammatory
      signs) were inspected by a physician. RESULTS: A subjective reduction in the
      number of ulcers was observed in 72.7% of the patients. A decrease in the ulcer
      healing period was observed in 72.7% of the patients; 75.8% experienced
      improvement in VAS for pain. Objective inspection of the ulcers showed a
      reduction of numbers in 57.6% of the patients, and 78.8% of the ulcers showed a
      decrease in area. Among the inflammatory signs, swelling and local heat were
      significantly improved after treatment. No significant differences were found
      between the BD group and RAU group in subjective and objective parameters, except
      for inflammatory signs. No side-effects were observed. CONCLUSIONS: The topical
      application of 0.2% HA gel seems to be an effective and safe therapy in patients
      with recurrent oral ulcers; the study supports the use of HA in BD with oral
      ulcers.

PMID- 18093112
TI  - Promoting child and adolescent mental health in low and middle income countries.
AB  - Children and adolescents in low and middle income countries (LAMIC) constitute 35
      50% of the population. Although the population in many such countries is
      predominantly rural, rapid urbanisation and social change is under way, with an
      increase in urban poverty and unemployment, which are risk factors for poor child
      and adolescent mental health (CAMH). There is a vast gap between CAMH needs (as
      measured through burden of disease estimates) and the availability of CAMH
      resources. The role of CAMH promotion and prevention can thus not be
      overestimated. However, the evidence base for affordable and effective
      interventions for promotion and prevention in LAMIC is limited. In this review,
      we briefly review the public health importance of CAM disorders in LAMIC and the
      specific issues related to risk and protective factors for these disorders. We
      describe a number of potential strategies for CAMH promotion which focus on
      building capacity in children and adolescents, in parents and families, in the
      school and health systems, and in the wider community, including structural
      interventions. Building capacity in CAMH must also focus on the detection and
      treatment of disorders for which the evidence base is somewhat stronger, and on
      wider public health strategies for prevention and promotion. In particular,
      capacity needs to be built across the health system, with particular foci on low
      cost, universally available and accessible resources, and on empowerment of
      families and children. We also consider the role of formal teaching and training
      programmes, and the role for specialists in CAMH promotion.

PMID- 18093113
TI  - Impact of familiarity upon children's developing facial expression recognition.
AB  - BACKGROUND: The impact of personal familiarity upon children's developing emotion
      processing has been largely ignored in previous research, yet may prove
      particularly important given the emotional salience of such stimuli and
      children's greater exposure to familiar others compared to strangers. We examined
      the impact of personal familiarity upon developing facial expression recognition
      (FER). METHODS: Participants included 153 children, 4-15 years old. We employed
      dynamic expressions of five emotions (happy, sad, anger, fear, disgust), posed by
      familiar (parents, teachers) and unfamiliar identities. RESULTS: Accuracy
      improved with age for recognising sad and fear expressions, but not anger.
      Children tended to correctly recognise happiness and fear at lower intensities.
      The impact of familiarity on FER depended on emotion-category. Familiarity did
      not affect recognition of sad expressions, but children were less accurate at
      recognising anger, fear, and disgust in familiar individuals compared to
      strangers. CONCLUSION: Personal familiarity may exert a distracting effect on
      children's performance. Findings highlight the importance of incorporating
      different emotion-categories and familiarity when examining the development of
      FER. Clinical implications are discussed.

PMID- 18093114
TI  - Early motherhood and subsequent life outcomes.
AB  - BACKGROUND: Early motherhood has been linked with a number of adverse outcomes,
      including mental health difficulties and barriers to completing educational
      qualifications and workforce participation. The present study examined the extent
      to which these linkages could be explained by the influence of social, family,
      and background factors that were associated with early motherhood. METHODS: Data
      were gathered as part of the Christchurch Health and Development Study, a 25-year
      longitudinal study of a birth cohort of New Zealand children. Information was
      obtained on: (a) the history of pregnancy and parenthood for female participants
      over the period 15-21 years; (b) measures of DSM-IV mental disorders and suicidal
      behaviour over the interval 21-25 years; (c) measures of educational achievement
      over the interval 21-25 years; (d) measures of welfare dependence, workforce
      participation, and income over the interval 21-25 years; and (e) childhood,
      family and related confounding factors. RESULTS: Early motherhood was associated
      with higher levels of mental health disorders, lower levels of educational
      achievement, higher levels of welfare dependence, lower levels of workforce
      participation, and lower income. Control for confounding factors reduced the
      associations between early motherhood and later mental health disorders to
      statistical non-significance. However, the associations between early motherhood
      and later educational achievement and economic circumstances persisted after
      control for potentially confounding factors. CONCLUSIONS: The findings suggest
      that early motherhood puts young women at risk for educational underachievement
      and poorer economic circumstances. The linkages between early motherhood and
      later mental health difficulties can largely be accounted for by childhood,
      family, and related circumstances that occurred prior to parenthood.

PMID- 18093115
TI  - Personality subtypes in adolescents with eating disorders: validation of a
      classification approach.
AB  - BACKGROUND: Research has identified three personality subtypes in adults with
      eating disorders (EDs): a high-functioning, an undercontrolled, and an
      overcontrolled group. The current study investigated whether similar personality
      prototypes exist in adolescents with EDs, and whether these personality
      prototypes show relationships to external correlates indicative of diagnostic
      validity. METHODS: Experienced clinicians from an adolescent practice-research
      network provided data on ED symptoms, DSM-IV comorbidity, personality pathology,
      and family and developmental history for 120 adolescent patients with EDs.
      RESULTS: Consistent with the findings from the adult literature, three types of
      personality pathology emerged in adolescents: High-functioning/Perfectionistic,
      Emotionally Dysregulated, and Avoidant/Depressed. The High-functioning prototype
      showed negative associations with comorbidity and positive associations with
      treatment response. The Emotionally Dysregulated prototype was specifically
      associated with externalizing Axis I and Cluster B Axis II disorders, poor school
      functioning, and adverse events in childhood. The Avoidant/Depressed prototype
      showed specific associations with internalizing Axis I and Clusters A Axis II
      disorders, poor peer relationships, poor maternal relationships, and
      internalizing disorders in first-degree relatives. CONCLUSIONS: These data
      support the presence of at least three diagnostically meaningful personality
      prototypes in adolescents with EDs, similar to those found previously in adults.
      Diagnosis of adolescents with EDs may be usefully supplemented by the assessment
      of personality style.

PMID- 18093116
TI  - Review: evaluating information systems in nursing.
AB  - AIMS: To review existing nursing research on inpatient hospitals' information
      technology (IT) systems in order to explore new approaches for evaluation
      research on nursing informatics to guide further design and implementation of
      effective IT systems. BACKGROUND: There has been an increase in the use of IT and
      information systems in nursing in recent years. However, there has been little
      evaluation of these systems and little guidance on how they might be evaluated.
      METHODS: A literature review was conducted between 1995 and 2005 inclusive using
      CINAHL and Medline and the search terms 'nursing information systems', 'clinical
      information systems', 'hospital information systems', 'documentation', 'nursing
      records', 'charting'. RESULTS: Research in nursing information systems was
      analysed and some deficiencies and contradictory results were identified which
      impede a comprehensive understanding of effective implementation. There is a need
      for IT systems to be understood from a wider perspective that includes aspects
      related to the context where they are implemented. CONCLUSIONS: Social and
      organizational aspects need to be considered in evaluation studies and realistic
      evaluation can provide a framework for the evaluation of information systems in
      nursing. RELEVANCE TO CLINICAL PRACTICE: The rapid introduction of IT systems for
      clinical practice urges evaluation of already implemented systems examining how
      and in what circumstances they work to guide effective further development and
      implementation of IT systems to enhance clinical practice. Evaluation involves
      more factors than just involving technologies such as changing attitudes,
      cultures and healthcare practices. Realistic evaluation could provide
      configurations of context-mechanism-outcomes that explain the underlying
      relationships to understand why and how a programme or intervention works.

PMID- 18093117
TI  - A study to evaluate nurse-led on-treatment review for patients undergoing
      radiotherapy for head and neck cancer.
AB  - AIMS AND OBJECTIVES: To evaluate a nurse-led clinic for patients undergoing
      radiotherapy to the head and neck. BACKGROUND: The side effects of radiotherapy
      to the head and neck are superimposed on already significant physical and
      psychological morbidity. Medical review clinics tend to focus on treatment
      complications and there is evidence that specialist nurses can provide more
      holistic care for patients. However, doubts have been raised about the
      appropriateness of nurse-led review in this highly symptomatic and complex group.
      DESIGN: This evaluation compared medical on-treatment review (Phase 1) with a
      nurse-led clinic (Phase 2) for patients having radiotherapy to the head and neck,
      using an historical control group. METHODS: Twenty patients were reviewed by
      their consultant and 23 by a nurse specialist, using a clinic protocol. A mixed
      method approach to data collection was taken. Patients completed weekly quality
      of life questionnaires and were asked about their experiences of support and
      care. General practitioners completed a questionnaire about the communication
      received from the clinic. Checklists assessed the content of clinic
      consultations. RESULTS: Patients valued the relationship developed with the nurse
      specialist, had longer, more frequent consultations and were more often referred
      to the multidisciplinary team. The nurse specialist managed 83% of consultations
      without referral to the consultant. Few significant differences in quality of
      life were found between the groups. There were indications that oral and
      nutritional problems were managed more effectively in the nurse-led clinic,
      although emotional functioning was higher in the medical group. GPs were positive
      about the timing and content of information received. CONCLUSIONS: On-treatment
      review for patients with head and neck cancer can be effectively managed by a
      nurse specialist. Relevance to Practice. Radiotherapy nurse specialists make an
      important contribution to the supportive care of patients with head and neck
      cancer. More investment is required to maximize their contribution.

PMID- 18093118
TI  - Nursing work in Jordan: an example of nursing work in the Middle East.
AB  - AIM: The study aimed to investigate Jordanian nurses' perceptions of their role
      in clinical practice. BACKGROUND: The lack of regulation of nursing practice by
      the profession across the Middle East until now has led to each institution
      setting its own policies regarding the role of the nurse and the practice of
      nursing. No study to date has examined the role of the nurse working in the acute
      hospital environment nor explored the practice of nursing in this region. DESIGN
      AND METHODS: A cross-sectional questionnaire survey was conducted using a quota
      sample. A total of 348 medical-surgical staff nurses and practical nurses from
      the three healthcare sectors in Jordan participated in the study with a response
      rate of 77%. The results were analysed by constructing multiple response tables,
      chi-square test, anova and log-linear analysis. RESULTS: Staff nurses in Jordan
      were expected to carry out the majority of nursing care activities. The role of
      the practical nurse was limited to the physical and professional domains of
      nursing care. Activities requiring higher levels of emotional or intellectual
      labour and interdisciplinary communication were attributed only to the staff
      nurse. The majority of the respondents reported nursing had not been their first
      choice of career. Male nurses had a higher intention to leave the nursing
      profession. The predominant method of care delivery used by nurses was task
      oriented. CONCLUSION: There was a general consensus regarding what constituted
      the nurse's work in the clinical area across the three healthcare sectors in
      Jordan. Role delineation between the two levels of nurses was also clear. There
      is a need to move from task-oriented to patient-centred care to promote quality
      patient care. Relevance to clinical practice. This study explores the role of the
      nurse working in the acute hospital environment in Jordan.

PMID- 18093119
TI  - The effect of preoperative uncertainty and anxiety on short-term recovery after
      elective arthroplasty.
AB  - AIMS AND OBJECTIVES: This study examined the effect of preoperative anxiety and
      uncertainty on short-term physical and mental recovery after elective
      arthroplasty. BACKGROUND: Uncertainty and anxiety accompany all medical
      procedures. Although preoperative uncertainty plays a central role in the
      development of stress, only a few studies explicitly examine this issue in terms
      of its impact on postoperative recovery. DESIGN: Quazi-experimental study.
      METHODS: Two self-administered questionnaires were used to collect data, before
      and five to six days after surgery. Participants (n = 87) admitted for elective
      arthroplasty completed the study. RESULTS: Preoperative anxiety negatively
      affected postoperative recovery variables and preoperative uncertainty negatively
      affected mental and physical recovery after surgery. Furthermore, postoperative
      symptoms were related to the patients' subjective readiness to be discharged.
      CONCLUSIONS: Separately, reduction of preoperative anxiety and uncertainty could
      have a positive impact on postoperative recovery and on perceived readiness to be
      discharged. RELEVANCE TO CLINICAL PRACTICE: The unique contribution of each
      preoperative variable (uncertainty and anxiety) to postoperative recovery
      emphasizes the need for clinical and educational interventions that separately
      relieve uncertainty and anxiety.

PMID- 18093120
TI  - Diabetes self-management experience: a focus group study of Taiwanese patients
      with type 2 diabetes.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to understand and document the
      perspectives of Taiwanese patients with type 2 diabetes regarding the processes
      and strategies used to self-manage their chronic condition. BACKGROUND: The
      importance of patients learning self-management through self-regulation has been
      recognized in the literature, but little of this research has focused on skills
      to manage symptoms. Besides, studies about how patients self-manage their
      diabetes in term of patients' perspectives have been scant. Sociocultural context
      is also an influencing factor in disease management. METHODS: Focus groups were
      used to collect data from 41 adult participants with type 2 diabetes at three
      teaching hospitals located in southern Taiwan. The five focus groups ranged in
      size from six to ten people. The focus groups were recorded, transcribed and
      analysed. RESULTS: Three themes and ten subthemes were revealed. The first theme
      'the impact of the illness' includes three subthemes: facing the predicament of
      stigmatization, concern about inheritance of diabetes and seeking alternative
      therapy for hope. The second theme 'self-regulation process' includes four
      subthemes: struggling for diet control, adjusting to psychological barriers,
      identifying body response and developing strategies for dealing with diabetes.
      The third theme 'transformation process' includes three subthemes: resuming
      conventional illness, support from families and fellow patients and learning to
      live with the disease. CONCLUSIONS: Findings obtained from the themes of the
      study illustrated that self-management of patients with diabetes is highly
      related to their own sociocultural environment and experiences. Understanding the
      cultural features and the meaning of illness can help in the development of
      interventions tailored to the needs of this cultural group. RELEVANCE TO CLINICAL
      PRACTICE: The findings have important implications for healthcare providers to
      consider individuals' sociocultural backgrounds in which they make choices about
      their treatment and manage their illness. This recognition will enhance patients
      with diabetes to transform being active in self-management through the skills of
      self-regulation.

PMID- 18093121
TI  - Role perceptions and reported actual role content of hospital nurses in Mainland
      China.
AB  - AIM: The study aimed to explore nurses' views and experiences regarding their
      working roles in Mainland China. BACKGROUND: Ministry of Health guidance relating
      to the hospital nurse's role has been widely used in Mainland China since 1982
      but it does not adequately cover the development of new roles arising from recent
      health care system reforms. This has led to increasing concerns about the
      potential of role conflict and role ambiguity for nurses especially where role
      expectations are not reflected in actual role content leading to job
      dissatisfaction and higher turnover. METHODS: A cross-sectional survey design
      using postal questionnaires comprising demographic questions and four scales
      measuring role perception and actual role content, job satisfaction, occupational
      stress, role conflict and role ambiguity was used. Five hundred and twelve
      hospital nurses in Beijing participated representing a response rate of 81%.
      RESULTS: Most respondents reported that staff nurses should undertake most of the
      roles described in the domain of patients' physical care, psychosocial and
      communication and professional aspects of patient care and patient care
      management and there was overall consensus regarding the roles of other health
      care personnel. Further, they reported that nurses always or sometimes carried
      out these roles. Different role perceptions were reported across educational
      groups. Additionally, nurses' ratings of role perception and actual role content
      were related to their ratings of job satisfaction, occupational stress, role
      conflict and role ambiguity (p < 0.05). CONCLUSIONS: There was relative consensus
      regarding role perceptions but the role boundary between nursing and non-nursing
      work lacked clarity. The importance of role expectations is highlighted regarding
      job satisfaction and other components of working lives. Relevance to clinical
      practice. Acknowledgement of a potential gap between expectations and actual role
      of nurses provides the basis for developing strategies to reduce resulting
      occupational stress, role conflict and role ambiguity and increase job
      satisfaction. Additionally the findings provide a basis for international
      comparison of actual nurse role content and the potential support needs of nurses
      from Mainland China who move to work in other health care systems.

PMID- 18093122
TI  - Pathology of peripheral intrahepatic cholangiocarcinoma with reference to
      tumorigenesis.
AB  - Cholangiocarcinomas (CCs) are neoplasms with cholangiocyte differentiation, and
      may arise from cholangiocytes of the biliary tree and possibly cholangiocyte
      progenitor cells. Intrahepatic CCs can be divided into the perihilar and
      peripheral types. Peripheral CCs present grossly as a mass forming tumor, and
      histologically as an adenocarcinoma of varying shapes and phenotypes. Some
      peripheral CCs (ductular type) are characterized by: (i) a histological
      resemblance to reactive bile ductules; (ii) the expression of neural cell
      adhesion molecule (NCAM) and vimentin. This type shows: (i) grossly, a blurred
      border; and (ii) histologically, carcinoma cells replacing the adjoining
      hepatocytes at the border of the tumor. It is frequently associated with
      neutrophilic infiltration and also with granulocyte and granulocyte macrophage
      colony-stimulating factors. We propose to call this type "ductular CC." The other
      peripheral CC (duct type) includes ordinary adenocarcinoma with well to
      moderately differentiated tubular and micropapillary patterns and is negative for
      NCAM but positive for mucin. This type can be called "duct CC," and shows a
      rather compressive growth. Interestingly, CC components of combined
      hepatocellular CC share the features of ductular CC, suggesting that hepatic
      progenitor cells may be involved in the tumorigenesis of ductular CC. The
      biological behavior of ductular CC and duct CC remains obscure, and follow-up and
      molecular studies on these tumors are required in order for these two CCs to be
      recognized as disease entities, and so as to evaluate their carcinogenesis.

PMID- 18093123
TI  - Disseminated intravascular coagulation associated with cytomegalovirus infection
      in a patient with hepatitis C virus cirrhosis.

PMID- 18093124
TI  - Collection of biological and non-biological particles by new and used filters
      made from glass and electrostatically charged synthetic fibers.
AB  - Synthetic filters made from fibers carrying electrostatic charges and fiberglass
      filters that do not carry electrostatic charges are both utilized commonly in
      heating, ventilating, and air-conditioning (HVAC) systems. The pressure drop and
      efficiency of a bank of fiberglass filters and a bank of electrostatically
      charged synthetic filters were measured repeatedly for 13 weeks in operating HVAC
      systems at a hospital. Additionally, the efficiency with which new and used
      fiberglass and synthetic filters collected culturable biological particles was
      measured in a test apparatus. Pressure drop measurements adjusted to equivalent
      flows indicated that the synthetic filters operated with a pressure drop less
      than half that of the fiberglass filters throughout the test. When measured using
      total ambient particles, synthetic filter efficiency decreased during the test
      period for all particle diameters. For particles 0.7-1.0 mum in diameter,
      efficiency decreased from 92% to 44%. It is hypothesized that this reduction in
      collection efficiency may be due to charge shielding. Efficiency did not change
      significantly for the fiberglass filters during the test period. However, when
      measured using culturable biological particles in the ambient air, efficiency was
      essentially the same for new filters and filters used for 13 weeks in the
      hospital for both the synthetic and fiberglass filters. It is hypothesized that
      the lack of efficiency reduction for culturable particles may be due to their
      having higher charge than non-biological particles, allowing them to overcome the
      effects of charge shielding. The type of particles requiring capture may be an
      important consideration when comparing the relative performance of
      electrostatically charged synthetic and fiberglass filters. PRACTICAL
      IMPLICATIONS: Electrostatically charged synthetic filters with high initial
      efficiency can frequently replace traditional fiberglass filters with lower
      efficiency in HVAC systems because properly designed synthetic filters offer less
      resistance to air flow. Although the efficiency of charged synthetic filters at
      collecting non-biological particles declined substantially with use, the
      efficiency of these filters at collecting biological particles remained steady.
      These findings suggest that the merits of electrostatically charged synthetic
      HVAC filters relative to fiberglass filters may be more pronounced if collection
      of biological particles is of primary concern.

PMID- 18093125
TI  - On-site quantification of re-entry ratio of ventilation exhausts in multi-family
      residential buildings and implications.
AB  - In the worldwide spread of Severe Acute Respiratory Syndrome (SARS) in 2003,
      cluster of cases occurred in a number of large high-rise residential building
      blocks, especially in Hong Kong. In this study, we examined one of the most
      likely virus-spread mechanisms, which is related to the inter-flat or inter-zonal
      airflow through open-windows caused by buoyancy effects. Dual tracer gases of CO2
      and SF6 are employed simultaneously to quantify the amount of the exhaust air
      coming out of the upper part of the window of a floor that re-enters the lower
      part of the open-window at the immediate upper floor. It was found that the room
      air could contain up to 7% of the exhaust air from the lower floor, and this
      occurs at low wind conditions with a combination of indoor-outdoor temperature
      difference. The results can well explain the earlier governmental finding that
      DNA strings of SARS Corono-Virus were detected within the sampled deposits on the
      window sills of the upper floors of the two index patients' flats. The
      preliminary and yet alarming conclusion may be that, in high-rise buildings,
      windows flush with a flat facade can be a major route for the vertical spread of
      pathogen-containing aerosols. PRACTICAL IMPLICATIONS: The confirmation of the
      transmission route can have a number of implications to both building design and
      infectious disease control. With respect to the former, considerations should be
      given to minimize the inter-flat airflow via windows flush with facade for high
      rise buildings with natural ventilation; and with respect to the latter, more
      targeted and earlier intervention can be implemented in case of any highly
      infectious disease outbreaks.

PMID- 18093126
TI  - P-dichlorobenzene emission rates from moth repellents and leakage rates from
      cloth storage cases.
AB  - Emission rates of p-dichlorobenzene (pDCB) from five kinds of commercially
      available moth repellents and leakage rates from six kinds of commercially
      available cloth storage cases were measured. The emission rates from moth
      repellents immediately after purchase (E(max)), which were obtained as the slope
      of the total emission amount vs. time elapsed, were 0.0033 to 0.035 g/h at 25
      degrees C. Moth repellents from different manufacturers differed greatly in
      emission rates at 0.0033, 0.0060, and 0.011 g/h, even if the moth repellent
      pieces were of similar shape and initial weight. This is thought to be because
      emission rates depended on the diffusion resistance of the repellent packing
      material used by each manufacturer. Therefore, the manufacturer-specific apparent
      mass transfer coefficients (K) were calculated for each moth repellent from the
      measured emission rates and a calculated saturated concentration. The apparent
      mass transfer coefficient K and the concentration gradient between the in-case
      (inside a cloth storage case) bulk air and the air at the surface of a moth
      repellent (pDCB tablet) were used for the calculation of the general emission
      rates. The leakage rates, defined as the air-exchange rate for a cloth storage
      case, from six cloth storage cases ranged from 0.41 to 78/h. Despite the large
      difference (more than 100 times) in the leakage rates of the cloth storage cases,
      the differences in emission rates of pDCB from these cloth storage cases to the
      indoor environment were small (<30%). This is because the concentration gradients
      between the in-case bulk air and the air at the surface of a repellent piece were
      almost the same among the storage cases. This suggests that pDCB emissions from
      cloth storage cases into the indoor environment should be reduced by making the
      storage cases more tightly sealable so that the leakage rate is <0.01/h. The
      results of adsorption tests of pDCB onto woollen clothes showed that the
      adsorption of pDCB on the clothes was assumed to be very strong and the transfer
      between the gas phase and the cloth phase in the cloth storage case was assumed
      to be small. PRACTICAL IMPLICATIONS: The use of pDCB provides benefits such as
      moth control and deodorizing, but on the other hand, poses potential risks to
      human health. There is a risk-benefit tradeoff, i.e. a tradeoff between risks of
      pDCB to human health and benefit of moth control effects. The pDCB concentration
      in the cloth storage case and in the indoor air can be estimated by using
      emission rates and the leakage rates obtained in this study. By comparing the
      concentration to the deterrent efficiency of pDCB, the risk for the use of pDCB
      moth repellents can be managed.

PMID- 18093127
TI  - Lab-scale test of a ventilation system including a dielectric barrier discharger
      and UV-photocatalyst filters for simultaneous removal of gaseous and particulate
      contaminants.
AB  - A ventilation system including a dielectric barrier discharger (DBD) and UV
      photocatalyst (UVP) filters was designed and tested for simultaneous removal of
      gaseous and particulate contaminants in a test chamber. The DBD was used in the
      first stage of electrostatic precipitator (ESP) for particle charging and gas
      decomposition. An applied DC electric field was used in the second stage of ESP
      to collect the charged particles. UVP filters were then used to decompose gaseous
      species, such as formaldehyde (HCHO) and benzene, toluene, and xylene (BTX)
      including O3, which was inherently produced by the DBD. %Reductions in mass
      concentration of PM2.5 and number concentration of submicron particles were
      approximately 79.5% and 76.3%, respectively, after the ventilation with air
      cleaning system was operated for 5 h. Both HCHO and BTX were completely removed
      when the initial concentration of each gas was 1 ppm. PRACTICAL IMPLICATIONS:
      Indoor air quality (IAQ) problems, such as sick building syndrome (SBS), are
      caused by limited ventilation in high-rise buildings. To overcome these problems,
      DBD and UVP filters were applied into a lab-scale ventilation system for
      simultaneous removal of pollutant particles and gases. The data supplied in this
      study will be useful for designing any actual ventilation system after further
      research, including scale-up experiments.

PMID- 18093128
TI  - Theoretical study of simultaneous water and VOCs adsorption and desorption in a
      silica gel rotor.
AB  - One-dimensional partial differential equations were used to model the
      simultaneous water and VOC (Volatile Organic Compound) adsorption and desorption
      in a silica gel rotor which was recommended for indoor air cleaning. The
      interaction among VOCs and moisture in the adsorption and desorption process was
      neglected in the model as the concentrations of VOC pollutants in typical indoor
      environment were much lower than that of moisture and the adsorbed VOCs occupied
      only a minor portion of adsorption capacity of the rotor. Consequently VOC
      transfer was coupled with heat and moisture transfer only by the temperatures of
      the rotor and the air stream. The VOC transfer equations were solved by
      discretizing them into explicit up-wind finite differential equations. The model
      was validated with experimental data. The calculated results suggested that the
      regeneration time designed for dehumidification may be prolonged to allow
      complete removal of the VOC pollutants from the rotor. The regeneration
      temperature designed for dehumidification provides considerable efficiency for
      indoor air cleaning. The application of the model in estimating the cleaning
      capacity of the rotor for VOC pollutants was demonstrated. PRACTICAL
      IMPLICATIONS: Silica gel rotors, usually used to dehumidify air, were found to be
      effective to remove VOCs by experiments recently. But the removal characteristics
      of VOCs are different from that of moisture. Therefore, the rotor structure and
      operating parameters for dehumidification needs to be optimized for the use of
      removing moisture and VOCs. This paper gives a way for the optimization.

PMID- 18093129
TI  - Sensory pollution from bag filters, carbon filters and combinations.
AB  - Used ventilation filters are a major source of sensory pollutants in air handling
      systems. The objective of the present study was to evaluate the net effect that
      different combinations of filters had on perceived air quality after 5 months of
      continuous filtration of outdoor suburban air. A panel of 32 subjects assessed
      different sets of used filters and identical sets consisting of new filters.
      Additionally, filter weights and pressure drops were measured at the beginning
      and end of the operation period. The filter sets included single EU5 and EU7
      fiberglass filters, an EU7 filter protected by an upstream pre-filter (changed
      monthly), an EU7 filter protected by an upstream activated carbon (AC) filter,
      and EU7 filters with an AC filter either downstream or both upstream and
      downstream. In addition, two types of stand-alone combination filters were
      evaluated: a bag-type fiberglass filter that contained AC and a synthetic fiber
      cartridge filter that contained AC. Air that had passed through used filters was
      most acceptable for those sets in which an AC filter was used downstream of the
      particle filter. Comparable air quality was achieved with the stand-alone bag
      filter that contained AC. Furthermore, its pressure drop changed very little
      during the 5 months of service, and it had the added benefit of removing a large
      fraction of ozone from the airstream. If similar results are obtained over a
      wider variety of soiling conditions, such filters may be a viable solution to a
      long recognized problem. PRACTICAL IMPLICATIONS: The present study was designed
      to address the emission of sensory offending pollutants from loaded ventilation
      filters. The goal was to find a low-polluting solution from commercially
      available products. The results indicate that the use of activated carbon (AC)
      filters downstream of fiberglass bag filters can reduce the degradation of air
      quality that occurs with increasing particle loading. A more practical solution,
      yet comparably effective, is a stand-alone particle filter that incorporates AC.
      In either case, further testing under a variety of conditions is recommended
      before making design decisions regarding the type of filters best suited to
      efficient building operation.

PMID- 18093130
TI  - Evolution of bone mineral density in AIDS patients on treatment with
      zidovudine/lamivudine plus abacavir or lopinavir/ritonavir.
AB  - OBJECTIVES: The aim of the study was to determine the factors that may contribute
      to decreases in bone mineral density (BMD) in patients with AIDS. METHODS: This
      was a prospective, non-randomized study. Dual X-ray absorptiometry (DXA) was used
      to determine the BMD of the lumbar spine, femoral neck and distal radius in
      treatment-naive HIV-infected male patients with AIDS before and after 1 year of
      treatment with zidovudine (ZDV)/lamivudine (3TC) plus abacavir (ABC) or
      lopinavir/ritonavir (LPV/r). RESULTS: Basal DXA was performed in 50 patients with
      CD4 counts <200 cells/microL and/or any AIDS-defining condition. Thirty-two
      patients completed 1 year with full adherence (17 on ABC and 15 on LPV/r) and a
      second DXA was then performed. At baseline, 19% had osteopenia at the lumbar
      spine and 19% at the femoral neck. Low body weight was related to low BMD. After
      48 weeks, BMD loss was significant at the three locations. The percentage of BMD
      loss at the femoral neck tended to be greater in the lopinavir group (5.3 vs.
      3.2%, P=0.058). The differences became significant at the lumbar spine (5.7 vs.
      2.7%, P=0.044). In the multivariate analysis, the treatment with LPV/r remained
      associated with bone loss at the lumbar spine. CONCLUSIONS: Osteopenia is
      frequent in treatment-naive HIV-infected men with AIDS. Bone loss is higher with
      LPV/r-based regimens compared with triple nucleoside reverse transcriptase
      inhibitors.

PMID- 18093131
TI  - Post-exercise heart rate recovery in HIV-positive individuals on highly active
      antiretroviral therapy. Early indicator of cardiovascular disease?
AB  - BACKGROUND: HIV infection and its treatment, specifically protease inhibitor (PI)
      therapy, have been associated with an increased risk for cardiovascular disease.
      Heart rate recovery (HRR) following peak exercise is predictive of future
      cardiovascular events and mortality in the general population. Nothing is known
      regarding HRR in individuals infected with HIV on highly active antiretroviral
      therapy (HAART). SUBJECTS AND METHODS: HIV-positive subjects on HAART that
      included a PI (HIV+PI, n=19), HIV-positive subjects on HAART that did not include
      a PI (HIV+noPI, n=19) and HIV-seronegative age, gender and body mass index (BMI)
      matched controls (Cntl, n=15) underwent a graded maximal exercise test on a cycle
      ergometer to volitional exhaustion. A continuous electrocardiogram was recorded
      and HRR was monitored every 30 s for 2 min post exercise. RESULTS: HRR at 1.5 and
      2 min was significantly delayed in HIV-positive subjects both on and not on PI
      based HAART compared with controls (P<0.01). CONCLUSION: HRR is impaired in HIV
      positive individuals on HAART, whether or not the HAART includes a PI, compared
      with age, gender, BMI, and activity level matched HIV-seronegative controls.
      Abnormal HRR may reflect cardio-autonomic dysfunction and may be an independent
      risk factor for future cardiac events in HIV-positive individuals that receive
      HAART.

PMID- 18093132
TI  - The SSK2 MAPKKK of Candida albicans is required for oxidant adaptation in vitro.
AB  - The Ssk2p (MAPKKK) of Candida albicans was deleted and functions assigned based
      on phenotyping studies. SSK2 deletion was first attempted using the UAU1
      disruption method. All transformants lacking one copy of SSK2 appeared to be
      triploids, suggesting that the SSK2 is essential for the organism. To verify this
      observation, a strain was constructed in which one allele was deleted using the
      SAT1 flipper disruption method. The second allele was then placed under control
      of the on/off tetracycline-regulatable (TetR) promoter. The transcription of SSK2
      was measured by reverse transcriptase-PCR and although the promoter was somewhat
      leaky, transcript was significantly reduced in an ssk2/TetR-SSK2 transformant
      (AT2) in the presence of doxycycline. Strains AT1 and AT2 constructed using the
      SAT1 flipper and TetR promoter method, respectively, were studied phenotypically
      in different growth media to determine the role of Ssk2p in morphogenesis. The
      mutants were also compared under on/off conditions in the presence of 1.5 M NaCl
      and various types of oxidants. Strain AT2 demonstrated resistance to 1.5 M NaCl
      in the absence of doxycycline but was inhibited by 8 mM hydrogen peroxide.

PMID- 18093133
TI  - Molecular basis of resistance to cytochrome bc1 inhibitors.
AB  - Inhibitors of the mitochondrial respiratory chain enzyme cytochrome bc1
      (respiratory complex III) have been developed as antimicrobial agents. They are
      used in agriculture to control plant pathogenic fungi and in medicine against
      human pathogens, such as the malaria parasite Plasmodium falciparum, or
      Pneumocystis jiroveci (an opportunistic pathogenic fungus life-threatening in
      immuno-compromised patients). These respiratory inhibitors are thus effective
      against a broad range of important pathogens. Unfortunately, the problem of
      acquired resistance has rapidly emerged. A growing number of pathogen isolates
      resistant to inhibitor treatment have been reported, and this resistance is often
      linked to mutation within cytochrome b, one of the essential catalytic subunits
      of the complex. Saccharomyces cerevisiae is an invaluable model in order to
      assess the impact of the mutations on the sensitivity to the drugs, on the
      respiratory capacity and the fitness of cells. In this minireview, the
      inhibitors, their mode of action, and the mutations implicated in resistance and
      studied in yeast are briefly reviewed. Four mutations that are of particular
      importance in medicine and in agriculture are briefly reviewed and described in
      more detail and the molecular basis of resistance and of evolution of the
      mutations is discussed succinctly.

PMID- 18093134
TI  - Senescence in fungi: the view from Neurospora.
AB  - Some naturally occurring strains of fungi cease growing through successive
      subculturing, i.e., they senesce. In Neurospora, senescing strains usually
      contain intramitochondrial linear or circular plasmids. An entire plasmid or its
      part(s) integrates into the mtDNA, causing insertional mutagenesis. The
      functionally defective mitochondria replicate faster than the wild-type
      mitochondria and spread through interconnected hyphal cells. Senescence could
      also be due to spontaneous lethal nuclear gene mutations arising in the
      multinucleated mycelium. However, their phenotypic effects remain masked until
      the nuclei segregate into a homokaryotic spore, and the spore germinates to form
      a mycelium that is incapable of extended culturing. Ultimately the growth of a
      fungal colony ceases due to dysfunctional oxidative phosphorylation. Results with
      senescing nuclear mutants or growth-impaired cytoplasmic mutants suggest that
      mtDNA is inherently unstable, requiring protection by as yet unidentified nuclear
      gene-encoded factors for normal functioning. Interestingly, these results are in
      accord with the endosymbiotic theory of origin of eukaryotic cells.

PMID- 18093135
TI  - Chromosomally encoded small antisense RNA in Corynebacterium glutamicum.
AB  - The first observation of chromosomally encoded small antisense RNA in
      Corynebacterium glutamicum is reported. Transcription oriented in the reverse
      direction to the transcription of the genes cg1934 and cg1935 was demonstrated
      within the chromosomal cg1934-cg1935 intergenic region. The transcription was
      found to be increased after heat shock. The transcriptional start point of this
      RNA designated ArnA was localized 21 bp upstream of the cg1935 translational
      start point by primer extension analysis, when the total RNA was isolated from
      cells grown at 30 degrees C. After heat shock, the transcriptional start point of
      an additional species of ArnA RNA was detected 19 bp upstream of the cg1935
      translational start point. The stress-response sigma factor SigH was found to be
      involved in the synthesis of ArnA RNAs. The 3' end of the ArnA RNAs was
      identified using the 3'-rapid amplification of cDNA ends technique. The length of
      the two ArnA RNA species was thus determined to be 129 and 131 nt, respectively.
      The ArnA RNAs were found to overlap the 5'-untranslated region of the transcript
      of the cg1935 gene coding for a transcriptional regulator of the GntR family.
      These results suggest that the noncoding ArnA RNAs have a regulatory function.

PMID- 18093136
TI  - Catalase as a source of both X- and V-factor for Haemophilus influenzae.
AB  - Haemophilus influenzae requires two growth factors, designated factor X
      (porphyrin) and factor V (NAD). Mammalian catalases contain both bound heme and
      NADPH. This study shows that catalase can supply both factors X and V to H.
      influenzae in vitro, thus representing a potential in vivo source of these
      essential growth factors.

PMID- 18093137
TI  - Phenotypic and molecular characterization of TEM-116 extended-spectrum beta
      lactamase produced by a Shigella flexneri clinical isolate from chickens.
AB  - Extended-spectrum beta-lactamases (ESBLs) produced by a clinical isolate of
      Shigella flexneri from chickens were detected with confirmatory phenotypic tests
      of the Clinical and Laboratory Standards Institute, and minimum inhibitory
      concentrations of several antibacterial drugs against the isolate were determined
      by the twofold dilution method. The genotype and subtype of the ESBL-producing S.
      flexneri isolate were identified by PCR amplifying of ESBL genes and DNA
      sequencing analysis. The results revealed that the isolate was able to produce
      ESBLs. They were resistant to third-generation cephalosporins such as ceftiofur
      and ceftriaxone and showed characteristics of multidrug resistance. The ESBL gene
      from the S. flexneri isolate was of the TEM type. Sequence analysis indicated
      that the TEM-type gene had 99.1% and 99.2% identity to TEM-1D ESBL and TEM-1 beta
      lactamase, respectively, at the nucleotide level. The amino acid sequence
      inferred from the TEM-type gene revealed three substitutions compared with the
      TEM-1 and TEM-1D enzymes: Ser51Gly, Val82Ila and Ala182Val. When it was compared
      with TEM-116 (99.8% identity), there were only two mutations (A(151)G and
      T(403)C) in the TEM-type gene, resulting in the substitution of Ser to Gly at
      position 51 in the amino acid sequence. The TEM type was a TEM-116 derivative.

PMID- 18093138
TI  - The isolation, purification and biological activity of a novel antibacterial
      compound produced by Pseudomonas stutzeri.
AB  - A novel compound designated zafrin [4beta-methyl-5, 6, 7, 8 tetrahydro-1 (4beta
      H)-phenanthrenone] was isolated from a crude extract of a marine bacterium
      identified as Pseudomonas stutzeri. Zafrin showed strong antibacterial activity
      against both Gram-positive and Gram-negative bacteria. The compound was purified
      and its structure was elucidated by spectroscopic methods including 1H-nuclear
      magnetic resonance (NMR), 13C-NMR, 1D-NMR and 2D-NMR spectroscopy. It could be
      demonstrated that a purified solution of zafrin was active against several human
      pathogens, including Staphylococcus aureus, and Salmonella typhi. By contrast,
      zafrin did not inhibit the growth of eukaryotic organisms Candida albicans and
      Schizosaccharomyces pombe. The minimal inhibitory concentration for Gram-positive
      bacteria ranged from 50 to 75 microg mL(-1) and varied between 75 and 125 microg
      mL(-1) for Gram-negative bacteria. Zafrin lysed Bacillus subtilis cells grown in
      an osmotically protected medium, suggesting that it does not act upon the cell
      wall. Further investigation using B. subtilis indicated that the compound is
      bactericidal and is likely to target the cell membrane.

PMID- 18093139
TI  - Persistence of Legionella in hospital water supplies and nosocomial Legionnaires'
      disease.
AB  - The molecular epidemiology of clinical and environmental Legionella species
      isolates was studied in seven hospitals from 1989 to 2006. The number of
      environmental pulsed field gel electrophoresis (PFGE) patterns ranged from one to
      nine according to the hospital. Genomic PFGE pattern persistence was observed in
      71% of the hospitals, even after 17 years in some hospitals, and the relationship
      between environmental and clinical isolates was established. The isolates
      associated with hospital-acquired Legionnaires' disease corresponded to the
      persistent environmental PFGE patterns of Legionella pneumophila in potable water
      supplies.

PMID- 18093140
TI  - An epidemic of plasmids? Dissemination of extended-spectrum cephalosporinases
      among Salmonella and other Enterobacteriaceae.
AB  - CTX-M- and AmpC-type beta-lactamases comprise the two most rapidly growing
      populations among the extended-spectrum cephalosporinases. The evolution and
      dissemination of resistance genes encoding these enzymes occur mostly through the
      transmission of plasmids. The high prevalence of clinical isolates of
      Enterobacteriaceae producing the plasmid-mediated extended-spectrum
      cephalosporinases resembles an epidemic of plasmids, and has generated serious
      therapeutic problems. This review describes the emergence and worldwide spread of
      various classes of plasmid-mediated extended-spectrum cephalosporinases in
      Salmonella and other Enterobacteriaceae, the transfer mechanism of the plasmids,
      detection methods, and therapeutic choices.

PMID- 18093141
TI  - Active immunization of hamsters against Clostridium difficile infection using
      surface-layer protein.
AB  - Clostridium difficile is the leading cause of infectious antibiotic-associated
      diarrhoea, particularly among the elderly. Its surface-layer protein (SLP) was
      tested as a vaccine component in a series of immunization and challenge
      experiments with Golden Syrian hamsters, combined with different systemic and
      mucosal adjuvants. Some regimens were also tested in a nonchallenge BALB/c mouse
      model, enabling closer monitoring of the immune response. None of the regimens
      conferred complete protection in the hamster model, and antibody stimulation was
      variable within regimens, and generally modest or poor. Mice displayed stronger
      antibody responses to SLP compared with hamsters. Two hamsters of five given SLP
      with Ribi (monophosphoryl lipid A and synthetic trehalose dicorynomycolate)
      survived the challenge, as did two of three given SLP with Ribi and cholera
      toxin. This modest trend to protection is interpreted with caution, because the
      survivors had low anti-SLP serum antibody titres. The hamsters were an outbred
      line, and subject to more genetic variability than inbred animals; however,
      BALB/c mice also showed strongly variable antibody responses. There is a clear
      need for better adjuvants for single-component vaccines, particularly for mucosal
      delivery. The hamster challenge model may need to be modified to be useful in
      active immunization experiments with SLP.

PMID- 18093142
TI  - Identification of dominant bacterial phylotypes in a cadmium-treated forest soil.
AB  - The presence of heavy metals in soils can lead to changes in microbial community
      structure, characterized by the dominance of groups that are able to tolerate
      contamination. Such groups may provide good microbial indicators of heavy-metal
      pollution in soil. Through terminal restriction fragment length polymorphism (T
      RFLP) profiling, changes in the bacterial community structure of an acidic forest
      soil that had been incubated with cadmium (Cd) for 30 days were investigated. T
      RFLP revealed, in particular, three operational taxonomic units (OTUs) strongly
      dominating in relative abundance in the contaminated soil. By cloning of the
      amplified 16S rRNA genes and partial sequencing of 25 clones, these three
      dominant OTUs were phylogenetically characterized. One dominant OTU in the
      cadmium-contaminated soil was derived from Betaproteobacteria, genus
      Burkholderia, and the other two were from uncultured members of the class
      Actinobacteria, closely related to the genus Streptomyces. To confirm T-RFLP
      data, four primers were designed on the basis of this study's dominant sequences,
      targeting the OTUs corresponding to Burkholderia or Actinobacteria. Real-time PCR
      showed that Burkholderia target sequences were more abundant in cadmium-treated
      soil (7.8 x 10(7)+/- 3.0 x 10(7) targets g(-1) soil) than in untreated soil (4.0
      x 10(6)+/- 8.9 x 10(5) targets g(-1) soil). It was concluded that the genus
      Burkholderia includes species that may be particularly dominant under cadmium
      contamination.

PMID- 18093143
TI  - Covariation between zooplankton community composition and cyanobacterial
      community dynamics in Lake Blaarmeersen (Belgium).
AB  - The cyanobacterial community composition in the mesotrophic Lake Blaarmeersen was
      determined by denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S
      rRNA gene fragments during two consecutive years to assess the importance of
      different classes of explanatory variables (bottom-up and top-down factors,
      physical variables and phytoplankton) in cyanobacterial community dynamics. The
      most dominant cyanobacteria in Lake Blaarmeersen were Synechococcus (three
      genotypes), Limnothrix redekei and Anabaena/Aphanizomenon. Analyses of Similarity
      revealed that the cyanobacterial community in Lake Blaarmeersen differed
      significantly between the growing season and the winter season as well as between
      the epilimnion and hypolimnion during the stratified periods. Mantel tests
      revealed significant correlations between the DGGE data and bottom-up factors,
      physical variables, the phytoplankton community composition and, interestingly,
      the zooplankton community composition. In general, the zooplankton community
      composition (especially the cladoceran community) was more important in
      structuring the cyanobacterial community than the total zooplankton biomass. This
      study shows that grazing zooplankton communities can have a relatively strong
      impact on the cyanobacterial community dynamics and that this impact can be
      equally important as bottom-up processes regulated by nutrient concentrations
      and/or physical variables.

PMID- 18093144
TI  - Use of a novel nonantibiotic triple marker gene cassette to monitor high survival
      of Pseudomonas fluorescens SBW25 on winter wheat in the field.
AB  - Pseudomonas fluorescens SBW25 was tagged with a triple marker gene cassette
      containing gfp, encoding green fluorescent protein; luxAB, encoding luciferase;
      and telABkilA, encoding tellurite resistance, and the tagged strain was monitored
      in the first Swedish field release of a genetically modified microorganism (GMM).
      The cells were inoculated onto winter wheat seeds and the GMM cells (SBW25:tgl)
      were monitored in the field from September 2005 to May 2006 using plating,
      luminometry and microscopic analyses. Cell numbers were high on all sampling
      occasions and metabolically active cells were detected on all plant parts. Field
      results were similar to those obtained in a parallel phytotron study, although
      the amount of SBW25:tgl detected on shoots was significantly higher in the
      phytotron than in the field. After winter, cell counts were 100-fold higher on
      the roots and root-associated soil compared with prewinter measurements, although
      the cells had a lower relative metabolic activity. The wheat seeds were naturally
      infested with Microdochium nivale, but no treatment resulted in reduction of
      disease symptoms. No SWB25:tgl cells were ever found in bulk soil or uninoculated
      plants. The Swedish field trial results complement and contrast with prior field
      studies performed with the same parent organism in the United Kingdom under
      different soil, plant and climatic conditions.

PMID- 18093145
TI  - Nitrosomonas Nm143-like ammonia oxidizers and Nitrospira marina-like nitrite
      oxidizers dominate the nitrifier community in a marine aquaculture biofilm.
AB  - Zero-discharge marine aquaculture systems are an environmentally friendly
      alternative to conventional aquaculture. In these systems, water is purified and
      recycled via microbial biofilters. Here, quantitative data on nitrifier community
      structure of a trickling filter biofilm associated with a recirculating marine
      aquaculture system are presented. Repeated rounds of the full-cycle rRNA approach
      were necessary to optimize DNA extraction and the probe set for FISH to obtain a
      reliable and comprehensive picture of the ammonia-oxidizing community. Analysis
      of the ammonia monooxygenase gene (amoA) confirmed the results. The most abundant
      ammonia-oxidizing bacteria (AOB) were members of the Nitrosomonas sp. Nm143
      lineage (6.7% of the bacterial biovolume), followed by Nitrosomonas marina-like
      AOB (2.2% of the bacterial biovolume). Both were outnumbered by nitrite-oxidizing
      bacteria of the Nitrospira marina-lineage (15.7% of the bacterial biovolume).
      Although more than eight other nitrifying populations were detected, including
      Crenarchaeota closely related to the ammonia-oxidizer 'Nitrosopumilus maritimus',
      their collective abundance was below 1% of the total biofilm volume; their
      contribution to nitrification in the biofilter is therefore likely to be
      negligible.

PMID- 18093146
TI  - Pertussis vaccination and epilepsy--an erratic history, new research and the
      mismatch between science and social policy.
AB  - For over 50 years, concerns have been raised about the risk of pertussis vaccine
      induced childhood encephalopathy and epilepsy. This article reviews the
      scientific literature, and the social and historical context in which the
      scientific, public health and societal views have not always been aligned. Large
      scale studies of this issue have produced conflicting results, although the
      recent consensus is that the risk of vaccine-induced encephalopathy and/or
      epilepsy, if it exists at all, is extremely low. Risk estimates in the literature
      have included: risk of a febrile seizure 1 per 19,496 vaccinations; risk of an
      afebrile seizure 1 per 76,133 vaccinations; risk of encephalopathy after
      pertussis infection nil-3 cases per million vaccinations. A recent study showed
      that encephalopathy in 11 out of the 14 children studied, although previously
      attributed to vaccination, was in fact due an inherited genetic defect of the
      SCNIA gene that codes for the voltage gated neuronal sodium channel. This study
      is important because it provides a solid alternative explanation for the
      perceived pertussis vaccine-encephalopathy association. The interesting
      possibility is raised that the encephalopathy apparently due to pertussis itself
      may, in some cases, be due to an SCNIA mutation. It may also, by analogy, shed
      some light on the continuing debate about other serious long-term adverse effects
      of vaccination in general.

PMID- 18093147
TI  - Absence status epilepsy: delineation of a distinct idiopathic generalized
      epilepsy syndrome.
AB  - PURPOSE: Absence status epilepticus (AS) is a prolonged, generalized, and
      nonconvulsive seizure that may occur in various circumstances. We report a series
      of patients in whom recurrent, unprovoked, typical AS was the main clinical
      feature. METHOD: We retrospectively reviewed consecutive patients referred to our
      epileptic centers, on the following criteria: (1) recurrent, unprovoked episodes
      of typical AS representing the unique or the predominant seizure type, (2) at
      least one episode of AS recorded by video-EEG or by EEG only, and (3) clinical
      and EEG features fulfilling the criteria of idiopathic epilepsy. We excluded
      patients with situation-related AS. RESULTS: We found 11 such cases (5F, 6M). The
      onset of AS was after puberty or in early adulthood in most; no clear triggering
      factor could account for the recurrence of AS episodes; infrequent generalized
      tonic-clonic seizures, and, rarely, absences, could also occur. These patients
      had no family history of epilepsy, normal neurological evaluation, normal
      neuroimaging, interictal EEG showing generalized spike- and polyspike-wave
      discharges on a normal background, no photoparoxysmal response, variable response
      of AS to intravenous benzodiazepines, and usually good seizure control with
      valproate. This peculiar condition was misdiagnosed in most because of the
      unusual clinical presentation and of some atypical interictal EEG findings, often
      leading to the use of inappropriate drugs. CONCLUSION: Although there is some
      overlap with previously described epilepsy syndromes, specific and shared
      features point to the existence of a distinct epilepsy entity that we propose to
      name "absence status epilepsy." This syndrome expands the spectrum of idiopathic
      generalized epilepsies.

PMID- 18093148
TI  - Aborted and refractory status epilepticus in children: a comparative analysis.
AB  - PURPOSE: The aims of this retrospective study were: (1) to compare the
      demographics, clinical characteristics, etiology, and EEG findings of status
      epilepticus aborted with medication (ASE) and refractory status epilepticus
      (RSE), (2) to describe the treatment response of status epilepticus (SE), and (3)
      to determine predictors of long-term outcome in children with SE. METHODS:
      Medical records and EEG lab logs with ICD-9 diagnostic codes related to SE were
      reviewed. Patients younger than 18 years of age, hospitalized in 1994-2004 at the
      Mayo Clinic, Rochester, were included. RESULTS: One hundred fifty-four children
      had SE; 94 (61%) had ASE, and 60 (39.0%) had RSE. Family history of seizures,
      higher seizure frequency score, higher number of maintenance antiepileptic drugs
      (AEDs), nonconvulsive SE, and focal or electrographic seizures on initial EEG
      were associated with RSE by univariate analysis. In-hospital mortality was
      significantly higher in RSE (13.3%) than in ASE (2.1%). In the long term,
      survivors with RSE developed more new neurological deficits (p < 0.001) and more
      epilepsy (p < 0.004) than children with ASE. Children treated in a more
      aggressive fashion appeared to have better treatment responses (p < 0.001) and
      outcomes (p = 0.03). Predictors of poor outcome were long seizure duration (p <
      0.001), acute symptomatic etiology (p = 0.04), nonconvulsive SE (NCSE) (p =
      0.01), and age at admission <5 years (p = 0.05). DISCUSSION: Several patient and
      clinical characteristics are associated with development of RSE and poor outcome.
      Prospective, randomized trials that assess different treatment protocols in
      children with SE are needed to determine the optimal sequence and timing of
      medications.

PMID- 18093149
TI  - Clinical and psychopathological definition of the interictal dysphoric disorder
      of epilepsy.
AB  - PURPOSE: Different authors suggested the occurrence of a pleomorphic affective
      syndrome in patients with epilepsy named interictal dysphoric disorder (IDD). We
      sought to investigate whether IDD occurs only in patients with epilepsy and to
      validate IDD features against DSM-IV criteria. METHODS: Consecutive patients with
      a diagnosis of epilepsy (E) or migraine (M) have been assessed using the BDI,
      MDQ, and the Interictal Dysphoric Disorder Inventory (IDDI), a questionnaire
      specifically created to evaluate IDD symptoms. Diagnosis of current and lifetime
      DSM-IV Axis I disorders was established using the MINI Plus version 5.0.0.
      RESULTS: A total of 229 patients (E = 117; M = 112) were evaluated. Females were
      significantly more represented in the migraine group (E = 46.5% vs. M = 73.3% p =
      0.009), but there was no difference in age, duration of the disease, or education
      level. Patients with epilepsy were more likely to screen positively at MDQ (E =
      17% vs. M = 5.3% p = 0.006) and to have a diagnosis of bipolar disorder (E =
      14.5% vs. M = 4.5% p = 0.013) as compared to migraine patients. There was no
      between-groups difference in IDD prevalence (E = 17%; M = 18.7%) and IDDI total
      scores (E = 4.1 +/- 2.0 vs. M = 3.8 +/- 2.0). Validation of IDD against DSM-IV
      categories showed current major depression being the foremost diagnostic category
      correlated with IDD in both epilepsy (OR = 0.32-0.12-0.88, p = 0.028) and
      migraine (OR = 0.10, 95% CI = 0.02-0.49, p = 0.004) samples. Current anxiety
      disorder correlated with IDD only in migraine patients (OR = 0.19, 95% CI = 0.05
      0.77, p = 0.02). CONCLUSION: IDD represents a homogenous construct that can be
      diagnosed in a relevant proportion of patients but it is not typical only of
      epilepsy, occurring in other central nervous system disorders such as migraine.

PMID- 18093150
TI  - Idiopathic hypertrophic pachymeningitis causing seizures.

PMID- 18093151
TI  - Side-to-side differences in pressure pain thresholds and pericranial muscle
      tenderness in strictly unilateral migraine.
AB  - Previous studies dealing with pressure pain sensitivity or muscle tenderness in
      migraine have shown conflicting results. Our aim was to explore the differences
      in mechanical pain sensitivity and pericranial muscle tenderness between patients
      with unilateral migraine and healthy controls, and to analyse side-to-side
      differences in both study groups. Pressure pain thresholds (PPT) at cephalic and
      neck points, plus local and total tenderness scores were blindly assessed in 25
      patients with strictly unilateral migraine and 25 healthy subjects. For PPT in
      the neck there were significant differences between groups (F = 47.029; P <
      0.001) and sides (F = 6.363; P < 0.01), and a significant interaction between
      group and side (F = 5.201; P = 0.02), while PPT in the cephalic point showed
      differences between groups (F = 11.774; P < 0.001), but not sides (F = 2.838; P =
      0.1). The total tenderness score showed significant differences between groups (F
      = 6.800; P < 0.01) and sides (F = 17.699; P < 0.001), along with a significant
      interaction between group and side (F = 14.420; P < 0.001). Patients had lower
      PPT and increased pericranial tenderness on the symptomatic side as compared with
      the non-symptomatic side and to either side in controls (P < 0.001), whereas no
      significant differences were identified between the non-symptomatic side and
      controls (P > 0.9). In migraine patients, PPT levels and muscle tenderness scores
      were negatively correlated (P < 0.001). The enhancement of local tenderness
      scores was related to hyperesthesia of specific muscles (sternocleidomastoid,
      suboccipital, and temporalis) rather than a generalized pericranial tenderness.
      Future studies should investigate the neuro-physiological basis for the
      laterality of allodynic and hyperalgesic responses in unilateral migraine.

PMID- 18093152
TI  - Progressive dementia and mesiotemporal atrophy on brain MRI: neurosyphilis
      mimicking pre-senile Alzheimer's disease?

PMID- 18093153
TI  - The tau S305S mutation causes frontotemporal dementia with parkinsonism.
AB  - Members of families with mutations in the tau gene are known to be heterogeneous
      in their clinical presentation, ranging from frontotemporal dementia to a
      clinical picture more resembling corticobasal degeneration or progressive
      supranuclear palsy. In this report, we describe a new phenotype for the tau S305S
      mutation, previously described as progressive supranuclear palsy. Clinically, the
      three affected family members showed alterations in personality and behaviour as
      well as cognitive decline and late levodopa-resistant parkinsonian symptoms,
      consistent with the diagnosis of frontotemporal dementia with parkinsonism linked
      to chromosome 17. One autopsied case displayed degeneration of the frontal and
      temporal lobes together with extensive tau pathology in both neurones and glial
      cells. Sarkosyl-soluble and -insoluble tau extracted from frontal cortex revealed
      a ratio shift with decreased levels of tau with three microtubule-binding repeats
      and increased levels of tau with four microtubule-binding repeats (4R tau). These
      findings provide further evidence for the clinical and pathological variation
      both within and between families with mutations in the tau gene. In addition,
      they support previous studies which demonstrate that the S305S mutation
      influences the splicing of tau exon 10 and results in an overproduction of 4R
      tau.

PMID- 18093154
TI  - Sodium lactate differently alters relative EEG power and functional connectivity
      in Alzheimer's disease patients' brain regions.
AB  - Bilateral temporo-parietal hypoperfusion and decreased glucose metabolism are
      characteristic in vivo findings in Alzheimer's disease (AD). Lactate is a
      metabolic vasodilator and is known to induce increased cerebral blood flow in
      healthy adults. The present study addresses the issue whether sodium lactate
      infusion affects functional state and resulting electroencephalographic patterns
      of AD patients. Twelve late-onset sporadic AD probands participated in this self
      control study. The relative power and synchronization likelihood (SL) values of
      the electroencephalographic samples were calculated and compared off-line before
      and after sodium lactate infusion (0.5 M, 5 ml/kg body weight). Based on the
      reactivity to sodium lactate the scalp could be divided into three parts; no
      significant changes were seen in the seriously damaged (P3-P4) areas. The
      moderately affected regions in the close neighborhood showed a paradoxic
      inactivation with electroencephalographic slowing, a likely consequence of the
      metabolic-like steal effect of the near-normal areas outside. These results
      indicate a diminished vascular and/or metabolic reserve capacity to sodium
      lactate challenge in AD and confirm the formerly described
      electroencephalographic abnormalities.

PMID- 18093155
TI  - Recombinant human erythropoietin administration protects cortical neurons from
      traumatic brain injury in rats.
AB  - We explored the regulation of erythropoietin and erythropoietin receptor on
      traumatic brain injury (TBI), as well as the antiapoptotic effects of recombinant
      human erythropoietin (rhEPO) treatment. Female Wistar rats were randomly divided
      into three groups: rhEPO-treated TBI, vehicle-treated TBI, and sham-operated. TBI
      was induced by the Feeney free falling model. Rats were killed 5, 12, 24, 72,
      120, or 168 h after TBI. Regulation of EPO, EPOR and Bcl-2 was detected by
      reverse transcription-polymerase chain reaction (RT-PCR), western blotting and
      immunofluorescence. Terminal deoxynucleotidyl transferase-mediated biotin-dUTP
      nick-end labeling (TUNEL) was used to assess DNA fragmentation after TBI.
      Induction of EPOR expression persisted for 168 h after TBI, whereas EPO was only
      slightly elevated for 72 h. In the rhEPO-treated TBI, Bcl-2 mRNA and protein
      levels were greater than in the vehicle-treated TBI. Bcl-2 mRNA peaked at 24 h
      and remained stable for 72-120 h. The number of TUNEL-positive cells in the rhEPO
      treated TBI was far fewer than in the vehicle-treated TBI. EPOR regulation is
      enhanced for almost a week after TBI. Administration of rhEPO protects neurons by
      enhancing Bcl-2 expression, thereby inhibiting TBI-induced neuronal apoptosis.

PMID- 18093156
TI  - Lack of evidence for an association between UCHL1 S18Y and Parkinson's disease.
AB  - UCHL1 has been proposed as a candidate gene for Parkinson's disease (PD). A meta
      analysis of white and Asian subjects reported an inverse association between the
      non-synonymous UCHL1 S18Y polymorphism and PD risk. However, this finding was not
      replicated in a large case-control study and updated meta-analysis restricted to
      white subjects. We performed a case-control study of 1757 PD patients recruited
      from movement disorder clinics and 2016 unrelated controls from four regions of
      the United States. All subjects self-reported as white. We did not observe
      evidence for an association between S18Y genotypes and PD (overall P-value for
      association: P = 0.42). After adjustment for age, sex, and recruitment region,
      the odds ratio for Y/S versus S/S was 0.91 (95% CI: 0.78-1.06) and for Y/Y versus
      S/S was 0.87 (95% CI: 0.58-1.29). We also did not observe a significant
      association for recessive or dominant models of inheritance, or after
      stratification by age at onset, age at blood draw, sex, family history of PD, or
      recruitment region. Our results suggest that UCHL1 S18Y is not a major
      susceptibility factor for PD in white populations although we cannot exclude the
      possibility that the S18Y variant exerts weak effects on risk, particularly in
      early-onset disease.

PMID- 18093157
TI  - Presence of vancomycin and ampicillin-resistant Enterococcus faecium of epidemic
      clonal complex-17 in wastewaters from the south coast of England.
AB  - The occurrence and diversity of vancomycin-resistant enterococci (VRE) in
      wastewaters from the Brighton and Hove area of south-east England were
      investigated. VRE were recovered from 71% of raw urban wastewater samples, 22% of
      treated urban wastewater samples, 15% of hospital wastewater sample and 33% of
      farm wastewater samples. Two hundred and eighty-eight isolates were typed and
      identified and the minimum inhibitory concentrations (MICs) to six antibiotics
      were determined for selected VRE. Vancomycin-resistant Enterococcus faecium
      (VREF) strains with a vancomycin MIC of more than 32 mug ml(-1) were examined by
      polymerase chain reaction for the vanA, vanB and esp genes. Twenty-three VREF
      with the vanA or vanB gene were further analysed by multilocus sequence typing
      which revealed that a cluster of VREF from both hospital and urban wastewaters
      belonged to the high-risk, epidemic, clonal complex-17 (CC17). Vancomycin
      resistant Enterococcus faecium belonging to the CC17 group contained the purK-1
      allele, were resistant to ampicillin and frequently ciprofloxacin, and usually
      contained the esp gene. To the authors' knowledge, this is the first report of
      CC17 strains isolated from urban wastewaters in the UK, and indicates that
      certain clones carrying antibiotic resistance or virulence traits indicative of
      the hospital environment can be detected in the urban wastewater system.

PMID- 18093158
TI  - Diversity of the active methanotrophic community in acidic peatlands as assessed
      by mRNA and SIP-PLFA analyses.
AB  - The active methanotroph community was investigated for the first time in heather
      (Calluna)-covered moorlands and Sphagnum/Eriophorum-covered UK peatlands. Direct
      extraction of mRNA from these soils facilitated detection of expression of
      methane monooxygenase genes, which revealed that particulate methane
      monooxygenase and not soluble methane monooxygenase was probably responsible for
      CH(4) oxidation in situ, because only pmoA transcripts (encoding a subunit of
      particulate methane monooxygenase) were readily detectable. Differences in
      methanotroph community structures were observed between the Calluna-covered
      moorland and Sphagnum/Eriophorum-covered gully habitats. As with many other
      Sphagnum-covered peatlands, the Sphagnum/Eriophorum-covered gullies were
      dominated by Methylocystis. Methylocella and Methylocapsa-related species were
      also present. Methylobacter-related species were found as demonstrated by the use
      of a pmoA-based diagnostic microarray. In Calluna-covered moorlands, in addition
      to Methylocella and Methylocystis, a unique group of peat-associated type I
      methanotrophs (Gammaproteobacteria) and a group of uncultivated type II
      methanotrophs (Alphaproteobacteria) were also found. The pmoA sequences of the
      latter were only distantly related to Methylocapsa and also to the RA-14 group of
      methanotrophs, which are believed to be involved in oxidation of atmospheric
      concentrations of CH(4). Soil samples were also labelled with (13)CH(4), and
      subsequent analysis of the (13)C-labelled phospholipid fatty acids (PLFAs) showed
      that 16:1 omega 7, 18:1 omega 7 and 18:1 omega 9 were the major labelled PLFAs.
      The presence of (13)C-labelled 18:1 omega 9, which was not a major PLFA of any
      extant methanotrophs, indicated the presence of novel methanotrophs in this
      peatland.

PMID- 18093159
TI  - Unexpected co-occurrence of six bacterial symbionts in the gills of the cold seep
      mussel Idas sp. (Bivalvia: Mytilidae).
AB  - Bathymodioline mussels occur in chemosynthesis-based ecosystems such as cold
      seeps, hydrothermal vents and organic debris worldwide. Their key adaptation to
      these environments is their association with bacterial endosymbionts which ensure
      a chemosynthetic primary production based on the oxidation of reduced compounds
      such as methane and sulfide. We herein report a multiple symbiosis involving six
      distinct bacterial 16S rRNA phylotypes, including two belonging to groups not yet
      reported as symbionts in mytilids, in a small Idas mussel found on carbonate
      crusts in a cold seep area located north to the Nile deep-sea fan (Eastern
      Mediterranean). Symbionts co-occur within hosts bacteriocytes based on
      fluorescence in situ hybridizations, and sequencing of functional genes suggests
      they have the potential to perform autotrophy, and sulfide and methane oxidation.
      Previous studies indicated the presence of only one or two symbiont 16S rRNA
      phylotypes in bathymodioline mussels. Together with the recent discovery of four
      bacterial symbionts in the large seep species Bathymodiolus heckerae, this study
      shows that symbiont diversity has probably been underestimated, and questions
      whether the common ancestor of bathymodioline mussels was associated with
      multiple bacteria.

PMID- 18093160
TI  - An AbrB-like protein might be involved in the regulation of cylindrospermopsin
      production by Aphanizomenon ovalisporum.
AB  - Certain filamentous cyanobacteria, including Aphanizomenon ovalisporum, are
      potentially toxic owing to the formation of the hepatotoxin cylindrospermopsin.
      We previously identified a gene cluster in A. ovalisporum likely to be involved
      in cylindrospermopsin biosynthesis, including amidinotransferase (aoaA) and
      polyketide-synthase (aoaC), transcribed on the reverse strands. Analysis of the
      genomic region between aoaA and aoaC identified two transcription start points
      for each of these genes, differentially expressed under nitrogen and light stress
      conditions. The transcript abundances of these genes and the cylindrospermopsin
      level were both affected by nitrogen availability and light intensity. Gel shift
      assays and DNA affinity columns isolated a protein that specifically binds to a
      150 bp DNA fragment from the region between aoaA and aoaC, and MS/MS analyses
      identified similarity to AbrB in other cyanobacteria and in Bacillus sp.
      Comparison of the native AbrB isolated from A. ovalisporum with that obtained
      after cloning and overexpression of abrB in Escherichia coli identified specific
      post-translational modifications in the native cyanobacterial protein. These
      modifications, which are missing in the protein expressed in E. coli, include N
      acetylation and methylation of specific residues. We discuss the possible role of
      these modifications in the regulation of cylindrospermopsin production in
      Aphanizomenon.

PMID- 18093161
TI  - Retrieval of entire genes from environmental DNA by inverse PCR with pre
      amplification of target genes using primers containing locked nucleic acids.
AB  - We had been unsuccessful to amplify desired nucleotide sequences from various
      environmental DNA samples by using the inverse polymerase chain reaction (IPCR)
      technique, most probably because the copy numbers of target DNA sequences had
      been quite low. To enrich the target DNA sequences prior to IPCR, a rolling
      circle amplification was used with a site-specific primer containing locked
      nucleic acids (LNAs). This pre-amplified IPCR (PAI-PCR) method increased the
      sensitivity of PCR almost 10,000 times compared with the standard IPCR in model
      experiments using Escherichia coli. We then applied the PAI-PCR method to isolate
      glycosyl hydrolase genes from DNAs extracted from vermiform appendixes of horses
      and termite guts. The flanking sequences of the target genes were amplified and
      cloned successfully using PAI-PCR, whereas standard IPCR resulted in no
      amplification.

PMID- 18093162
TI  - Growth phase-dependent switch in osmolyte strategy in a moderate halophile:
      ectoine is a minor osmolyte but major stationary phase solute in Halobacillus
      halophilus.
AB  - The moderately halophilic, chloride-dependent bacterium Halobacillus halophilus
      switches its osmolyte strategy with the salinity in its environment by the
      production of different compatible solutes. Ectoine is produced predominantly at
      very high salinities, along with proline. Interestingly, ectoine production is
      growth phase dependent which led to a more than 1000-fold change in the ectoine :
      proline ratio from 0.04 in exponential to 27.4 in late stationary phase cultures.
      The genes encoding the ectoine biosynthesis pathway were identified on the
      chromosome in the order ectABC. They form an operon that is expressed in a
      salinity-dependent manner with low-level expression below 1.5 M NaCl but 10-fold
      and 23-fold increased expression at 2.5 and 3.0 M NaCl respectively. The temporal
      expression of genes involved in osmoresponse is different with gdh/gln and pro
      genes being first, followed by ect genes. Chloride had no effect on expression of
      ect genes, but stimulated cellular EctC synthesis as well as ectoine production.
      These data demonstrate, for the first time, a growth-phase dependent switch in
      osmolyte strategy in a moderate halophile and, additionally, represent another
      piece of the chloride regulon of H. halophilus.

PMID- 18093163
TI  - Fluorescent properties of c-type cytochromes reveal their potential role as an
      extracytoplasmic electron sink in Geobacter sulfurreducens.
AB  - A novel fluorescence technique for monitoring the redox status of c-type
      cytochromes in Geobacter sulfurreducens was developed in order to evaluate the
      capacity of these extracytoplasmic cytochromes to store electrons during periods
      in which an external electron acceptor is not available. When intact cells in
      which the cytochromes were in a reduced state were excited at a wavelength of 350
      nm, they fluoresced with maxima at 402 and 437 nm. Oxidation of the cytochromes
      resulted in a loss of fluorescence. This method was much more sensitive than the
      traditional approach of detecting c-type cytochromes via visible light
      absorbance. Furthermore, fluorescence of reduced cytochromes in individual cells
      could be detected via fluorescence microscopy, and the cytochromes in a G.
      sulfurreducens biofilm, remotely excited with an optical fibre, could be detected
      at distances as far as 5 cm. Fluorescence analysis of cytochrome oxidation and
      reduction of the external electron acceptor, anthraquinone-2,6-disulfonate,
      suggested that the extracytoplasmic cytochromes of G. sulfurreducens could store
      approximately 10(7) electrons per cell. Independent analysis of the haem content
      of the cells determined from analysis of incorporation of (55)Fe into cytochromes
      provided a similar estimate of cytochrome electron-storage capacity. This
      electron-storage capacity could, in the absence of an external electron acceptor,
      permit continued electron transfer across the inner membrane sufficient to supply
      the maintenance energy requirements for G. sulfurreducens for up to 8 min or
      enough proton motive force to power flagella motors for G. sulfurreducens
      motility. The fluorescence approach described here provides a sensitive method
      for evaluating the redox status of Geobacter species in culture and/or its
      environments. Furthermore, these results suggest that the periplasmic and outer
      membrane cytochromes of Geobacter species act as capacitors, allowing continued
      electron transport, and thus viability and motility, for Geobacter species as
      they move between heterogeneously dispersed Fe(III) oxides during growth in the
      subsurface.

PMID- 18093164
TI  - Characterization of true-branching cyanobacteria from geothermal sites and hot
      springs of Costa Rica.
AB  - Costa Rica is at the centre of the Mesoamerican biodiversity hotspot. Little is
      known about cyanobacteria from this region so far. Here, four isolates of the
      order Stigonematales (section V) were characterized in a polyphasic approach. All
      strains were isolated from geothermal sites and hot springs of Costa Rica.
      However, one of them, identified as Westiellopsis sp. Ar73, did not grow at more
      than 40 degrees C. Based on its identical 16S rRNA to several previously isolated
      Westiellopsis sp. and Fischerella muscicola strains, a ubiquitous distribution
      throughout tropical and subtropical regions can be implied. In contrast, the
      isolates MV9, MV11 and RV14 grew well up to 50-55 degrees C. Based on
      morphologic, ultrastructural, molecular and physiologic data, MV9, MV11 and RV14
      were identified to belong to the genus Fischerella. Two distinct intergenic
      transcribed spacer (ITS) types, with or without tRNA genes, were detected for all
      Stigonematales analysed here, indicating ITS polymorphism as a characteristic
      feature of heterocystous cyanobacteria. In phylogenetic trees, these Fischerella
      spp. formed a new and distinct clade within the wider lineage of thermophilic
      Fischerella (Mastigocladus cf. laminosus), which might represent a geographic
      lineage. Thus, geographic isolation may be an underestimated aspect of microbial
      evolution. The strains presented here are suitable as new models to study this
      group of cyanobacteria.

PMID- 18093165
TI  - Polysaccharide hydrolysis in aggregates and free enzyme activity in aggregate
      free seawater from the north-eastern Gulf of Mexico.
AB  - Marine snow aggregates represent hotspots of carbon remineralization in the
      ocean. Various aspects of bacterial dynamics have been investigated on marine
      snow. To date, extracellular enzymatic activities in aggregates have been
      measured using small substrate proxies that do not adequately reflect the
      complexity of biomacromolecules such as polysaccharides, proteins and lipids. To
      address this issue, we used six structurally distinct, fluorescently labelled
      polysaccharides to measure enzymatic hydrolysis on aggregates formed with a
      roller table and in aggregate-free (ambient) seawater from two near-coast sites,
      north-eastern Gulf of Mexico. A single polysaccharide was incubated in aggregates
      and ambient seawater. Changes in polysaccharide molecular weight were monitored
      over time to measure the course of enzymatic hydrolysis. All six polysaccharides
      were hydrolysed in aggregates, indicating a broad range of enzyme activities in
      aggregate-associated bacteria. Four substrates were also hydrolysed in ambient
      waters. Epifluorescence microscopy revealed that nearly all of the bacteria
      present in original waters were incorporated into aggregates. Therefore
      hydrolytic activities in ambient waters were presumably due to enzymes spatially
      disconnected from cells and aggregates. Our results show substantial enzymatic
      activity in cell/aggregate-free seawater, suggesting a significant role of free
      enzymes in hydrolytic activity in waters from the north-eastern Gulf of Mexico.

PMID- 18093166
TI  - Overlapping representations of the neck and whiskers in the rat motor cortex
      revealed by mapping at different anaesthetic depths.
AB  - The primary motor cortex of mammals has an orderly representation of different
      body parts. Within the representation of each body part the organization is more
      complex, with groups of neurons representing movements of a muscle or a group of
      muscles. In rats, uncertainties continue to exist regarding organization of the
      primary motor cortex in the whisker and the neck region. Using intracortical
      microstimulation (ICMS) we show that movements evoked in the whisker and the neck
      region of the rat motor cortex are highly sensitive to the depth of anaesthesia.
      At light anaesthetic depth, whisker movements are readily evoked from a large
      medial region of the motor cortex. Lateral to this is a small region where
      movements of the neck are evoked. However, in animals under deep anaesthesia
      whisker movements cannot be evoked. Instead, neck movements are evoked from this
      region. The neck movement region thus becomes greatly expanded. An analysis of
      the threshold currents required to evoke movements at different anaesthetic
      depths reveals that the caudal portion of the whisker region has dual
      representation, of both the whisker and the neck movements. The results also
      underline the importance of carefully controlling the depth of anaesthesia during
      ICMS experiments.

PMID- 18093167
TI  - Spatiotemporal loss of K+ transport proteins in the developing cochlear lateral
      wall of guinea pigs with hereditary deafness.
AB  - Genetic deafness is one of the most common human genetic birth defects. To
      understand the molecular mechanisms underlying human hereditary deafness, deaf
      animal strains have proved to be invaluable models. The German waltzing guinea
      pig is a new strain of animals with unidentified gene mutation(s), displaying
      recessively inherited cochleovestibular impairment. Histological investigations
      of the homozygous animals (gw/gw) revealed a collapse of the endolymphatic
      compartment and malformation of stria vascularis. RT-PCR showed a significant
      reduction in expression of the strial intermediate cell-specific gene Dct and the
      tight-junction gene Cldn11 in the embryonic day (E)40 and adult gw/gw cochlear
      lateral wall. Immunohistochemical analysis of the gw/gw cochlea showed loss of
      the tight junction protein CLDN11 in strial basal cells from E40, loss of the
      potassium channel subunit KCNJ10 in strial intermediate cells from E50, and loss
      of the Na-K-Cl cotransporter SLC12A2 in strial marginal cells from E50. In
      addition, a temporary loss of the gap junction protein GJB2 (connexin 26) between
      fibrocytes in the spiral ligament of the E50 gw/gw cochlea was observed. The
      barrier composed of tight junctions between strial basal cells was disrupted in
      the gw/gw cochlea as indicated by a biotin tracer permeability assay. In
      conclusion, spatiotemporal loss of K+ transport proteins in the cochlear lateral
      wall is caused by malformation of the stria vascularis in the developing German
      waltzing guinea pig inner ear. This new animal strain may serve as a good model
      for studying human genetic deafness due to disruption of inner ear ion
      homeostasis.

PMID- 18093168
TI  - Motor cortical control of internal pallidal activity through glutamatergic and
      GABAergic inputs in awake monkeys.
AB  - The internal segment of the globus pallidus (GPi) receives motor-related cortical
      signals mainly through the striatum, the external segment of the globus pallidus
      (GPe) and the subthalamic nucleus (STN). The GPi sends its outputs outside the
      basal ganglia and plays a key role in motor control. Extracellular unit
      recordings were performed in awake monkeys to explore how glutamatergic STN
      inputs and GABAergic striatal and GPe inputs control spontaneous activity and how
      these inputs contribute to motor cortex stimulation-induced responses of GPi
      neurons. The typical responses of GPi neurons to cortical stimulation consisted
      of an early excitation, an inhibition and a late excitation. Local applications
      of the NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic
      acid and/or the AMPA/kainate receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3
      dioxo-benzo[f]quinoxaline-7-sulphonamide in the vicinity of recorded GPi neurons
      reduced the firing rate, and abolished or attenuated both early and late
      excitations following cortical stimulation. Local application of the GABA(A)
      receptor antagonist gabazine increased the firing rate, induced oscillatory
      firings and diminished the cortically induced inhibition. Muscimol or gabazine
      injection into the STN or GPe also altered the firing rate, and attenuated the
      late excitation of GPi neurons. The gabazine injection into the STN occasionally
      induced dyskinesia with significantly decreased GPi activity. These data suggest
      that the early and late excitations are glutamatergic and induced by the cortico
      STN-GPi and cortico-striato-GPe-STN-GPi pathways, respectively. The inhibition is
      GABAergic and induced by the cortico-striato-GPi pathway. In addition, these
      inputs are the main factors governing the spontaneous activity of GPi neurons.

PMID- 18093169
TI  - Alcohol-induced stress in painful alcoholic neuropathy.
AB  - Chronic alcohol consumption induces a painful small-fiber peripheral neuropathy,
      the severity of which increases during alcohol withdrawal. Chronic alcohol
      consumption also produces a sustained increase in stress hormones, epinephrine
      and corticosterone, that is exacerbated during alcohol withdrawal. We report that
      adrenal medullectomy and administration of a glucocorticoid receptor antagonist,
      mifepristone (RU 38486), both prevented and reversed a model of painful
      peripheral neuropathy in alcohol binge-drinking rats. Chronic administration of
      stress levels of epinephrine to rats that had undergone adrenal medullectomy and
      were being fed the alcohol diet reconstituted this phenotype. Intrathecal
      administration of oligodeoxynucleotides antisense to the beta(2)-adrenergic- or
      glucocorticoid-receptor also prevented and reversed the pro-nociceptive effects
      of ethanol. Our results suggest a convergence of the effects of mediators of the
      hypothalamic-pituitary- and sympathoadrenal-stress axes on sensory neurons in the
      induction and maintenance of alcohol-induced painful peripheral neuropathy.

PMID- 18093170
TI  - Context-specific sensitization of cocaine-induced locomotor activity and
      associated neuronal ensembles in rat nucleus accumbens.
AB  - Repeated cocaine administration to rats outside their home cage induces
      behavioral sensitization that is strongly modulated by the drug administration
      environment. We hypothesized that stimuli in the drug administration environment
      activate specific sets of striatal neurons, called neuronal ensembles, for
      further cocaine-enhanced activation, and that repeated activation of these
      neuronal ensembles underlies context-specific sensitization. In the present
      study, we repeatedly administered cocaine or saline to rats on alternate days in
      two distinct environments outside the home cage, one paired with cocaine and the
      other with saline. On test day, cocaine challenge injections in the cocaine
      paired environment produced strongly enhanced levels of locomotor activity, while
      cocaine challenge injections in the saline-paired environment did not. The
      corresponding record of past neuronal activation in nucleus accumbens and caudate
      putamen during repeated drug administration was assessed using FosB
      immunohistochemistry, while acute neuronal activation on test day was assessed
      using c-fos in situ hybridization. Although only 2% of striatal neurons were FosB
      labeled, 87% of these FosB-labeled neurons were co-labeled with c-fos when
      cocaine was injected in the cocaine-paired environment. The degree of co-labeling
      was significantly less following cocaine or saline challenge injections in the
      saline-paired environment. Furthermore, the total number of c-fos-labeled neurons
      was greater with either cocaine or saline challenge injections in the cocaine
      paired environment than in the saline-paired environment. These findings
      demonstrate that the drug administration environment partly determines which
      striatal neuronal ensembles are activated, and to what extent, following context
      specific sensitization to cocaine.

PMID- 18093171
TI  - Oxidative stress on EAAC1 is involved in MPTP-induced glutathione depletion and
      motor dysfunction.
AB  - Excitatory amino acid carrier 1 (EAAC1) is a glutamate transporter expressed on
      mature neurons in the CNS, and is the primary route for uptake of the neuronal
      cysteine needed to produce glutathione (GSH). Parkinson's disease (PD) is a
      neurodegenerative disorder pathogenically related to oxidative stress and shows
      GSH depletion in the substantia nigra (SN). Herein, we report that 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, an experimental model of
      PD, showed reduced motor activity, reduced GSH contents, EAAC1 translocation to
      the membrane and increased levels of nitrated EAAC1. These changes were reversed
      by pre-administration of n-acetylcysteine (NAC), a membrane-permeable cysteine
      precursor. Pretreatment with 7-nitroindazole, a specific neuronal nitric oxide
      synthase inhibitor, also prevented both GSH depletion and nitrotyrosine formation
      induced by MPTP. Pretreatment with hydrogen peroxide, L-aspartic acid beta
      hydroxamate or 1-methyl-4-phenylpyridinium reduced the subsequent cysteine
      increase in midbrain slice cultures. Studies with chloromethylfluorescein
      diacetate, a GSH marker, demonstrated dopaminergic neurons in the SN to have
      increased GSH levels after NAC treatment. These findings suggest that oxidative
      stress induced by MPTP may reduce neuronal cysteine uptake, via EAAC1
      dysfunction, leading to impaired GSH synthesis, and that NAC would exert a
      protective effect against MPTP neurotoxicity by maintaining GSH levels in
      dopaminergic neurons.

PMID- 18093172
TI  - Impaired nerve regeneration in reeler mice after peripheral nerve injury.
AB  - Reelin, an extracellular matrix protein, plays an important role in the
      regulation of neuronal migration and cortical lamination in the developing brain.
      Little is known, however, about the role of this protein in axonal regeneration.
      We have previously shown that Reelin is secreted by Schwann cells in the
      peripheral nerve compartment during postnatal development and that it is up
      regulated following nerve injury in adult mice. In this work, we generated mice
      deficient in Reelin (reeler) that express yellow fluorescent protein (YFP) in a
      subset of neurons and examined the axonal regeneration following nerve crush. We
      found that axonal regeneration was significantly altered compared with wild-type
      mice. By contrast, retrograde tracing with Fluorogold dye after sciatic nerve
      crush was unaffected in these mutants, being comparable with normal axonal
      transport observed in wild-type. These results indicate that the absence of
      Reelin impairs axonal regeneration following injury and support a role for this
      protein in the process of peripheral nerve regeneration.

PMID- 18093173
TI  - Conditioning of interictal behaviours, but not ictal behaviours, seizures or
      afterdischarge threshold, by kindling of the amygdala in rats.
AB  - Rats received 45 pairings of kindling or sham stimulation in distinctive contexts
      before a conditioned place preference/aversion test, to determine whether the
      stimulation and seizures were rewarding or punishing. After more pairings, rats
      received kindling stimulation in each context (switch test). Ictal measures in
      this test included afterdischarge duration, clonus duration, latency to clonus,
      class of convulsion and falls. After more pairings, afterdischarge threshold was
      measured in each context. On every fourth day of pairings, the rats' behaviour in
      the prestimulation interval was recorded, to measure conditioned anticipatory
      defensive behaviour. We partially replicated the finding of Barnes et al. (2001,
      Behav. Neurosci., 115, 1065-1072) that conditioned anticipatory responses and
      conditioned place aversion are associated with the kindling environment. However,
      there were no conditioned effects on any ictal measures, including afterdischarge
      threshold. Our results fail to support the hypothesis that conditioning is a
      universal mechanism for kindling.

PMID- 18093174
TI  - Computational significance of transient dynamics in cortical networks.
AB  - Neural responses are most often characterized in terms of the sets of
      environmental or internal conditions or stimuli with which their firing rate
      [corrected]increases or decreases are correlated [corrected] Their transient
      (nonstationary) temporal profiles of activity have received comparatively less
      attention. Similarly, the computational framework of attractor neural networks
      puts most emphasis on the representational or computational properties of the
      stable states of a neural system. Here we review a couple of neurophysiological
      observations and computational ideas that shift the focus to the transient
      dynamics of neural systems. We argue that there are many situations in which the
      transient neural behaviour, while hopping between different attractor states or
      moving along 'attractor ruins', carries most of the computational and/or
      behavioural significance, rather than the attractor states eventually reached.
      Such transients may be related to the computation of temporally precise
      predictions or the probabilistic transitions among choice options, accounting for
      Weber's law in decision-making tasks. Finally, we conclude with a more general
      perspective on the role of transient dynamics in the brain, promoting the view
      that brain activity is characterized by a high-dimensional chaotic ground state
      from which transient spatiotemporal patterns (metastable states) briefly emerge.
      Neural computation has to exploit the itinerant dynamics between these states.

PMID- 18093176
TI  - Adjunctive use of the non-ionic surfactant Poloxamer 188 improves fetal
      dopaminergic cell survival and reinnervation in a neural transplantation strategy
      for Parkinson's disease.
AB  - Although neural transplantation of fetal dopaminergic cells is a promising
      therapy for Parkinson's disease, poor transplanted cell survival limits its
      efficacy. In the present study it was hypothesized that the use of Poloxamer 188
      (P188), a non-ionic surfactant, during cell preparation and transplantation may
      protect cells from associated mechanical injury and thus improve transplanted
      cell survival in a rat model of Parkinson's disease. Fetal rat dopaminergic
      tissue was dissociated in media with or without P188 and then cultured for 1 week
      or transplanted into the striatum of rats with unilateral 6-hydroxydopamine
      lesions of the nigrostriatal dopaminergic pathway. Fetal dopaminergic cell
      survival and reinnervation of the host brain were examined using tyrosine
      hydroxylase immunohistochemistry and stereological quantification. The number of
      surviving tyrosine hydroxylase-immunoreactive cells in vitro and in vivo was
      significantly increased by 2.2-fold by incubating fetal dopaminergic cells with
      P188 during tissue dissociation. Furthermore, the striatal reinnervation in
      parkinsonian rats that received intrastriatal transplants of P188-exposed
      dopaminergic cells was significantly enhanced (1.8-fold increase) compared with
      rats that received non-P188-treated cells. In conclusion, P188 protects fetal
      dopaminergic cells from mechanical injury by increasing cell survival and
      enhances dopaminergic fibre outgrowth into the transplanted striatum. Use of P188
      may thus be an important adjunct to improve the clinical efficacy of neural
      transplantation for Parkinson's disease.

PMID- 18093175
TI  - The leaner P/Q-type calcium channel mutation renders cerebellar Purkinje neurons
      hyper-excitable and eliminates Ca2+-Na+ spike bursts.
AB  - The leaner mouse mutation of the Cacna1a gene leads to a reduction in P-type Ca2+
      current, the dominant Ca2+ current in Purkinje cells (PCs). Here, we compare the
      electro-responsiveness and structure of PCs from age-matched leaner and wild-type
      (WT) mice in pharmacological isolation from synaptic inputs in cerebellar slices.
      We report that compared with WT, leaner PCs exhibit lower current threshold for
      Na+ spike firing, larger subthreshold membrane depolarization, rapid adaptation
      followed by complete block of Na+ spikes upon strong depolarization, and fail to
      generate Ca2+-Na+ spike bursts. The Na+ spike waveforms in leaner PCs have slower
      kinetics, reduced spike amplitude and afterhyperpolarization. We show that a
      deficit in the P-type Ca2+ current caused by the leaner mutation accounts for
      most but not all of the changes in mutant PC electro-responsiveness. The
      selective P-type Ca2+ channel blocker, omega-agatoxin-IVA, eliminated differences
      in subthreshold membrane depolarization, adaptation of Na+ spikes upon strong
      current-pulse stimuli, Na+ spike waveforms and Ca2+-Na+ burst activity. In
      contrast, a lower current threshold for eliciting repetitive Na+ spikes in leaner
      PCs was still observed after blockade of the P-type Ca2+ current, suggesting
      secondary effects of the mutation that render PCs hyper-excitable. Higher input
      resistance, reduced whole-cell capacitance and smaller dendritic size accompanied
      the enhanced excitability in leaner PCs, indicative of developmental retardation
      in these cells caused by P/Q-type Ca2+ channel malfunction. Our data indicate
      that a deficit in P-type Ca2+ current leads to complex functional and structural
      changes in PCs, impairing their intrinsic and integrative properties.

PMID- 18093177
TI  - Developmental exposure to polychlorinated biphenyls PCB153 or PCB126 impairs
      learning ability in young but not in adult rats.
AB  - Polychlorinated biphenyls (PCBs) are persistent organic pollutants present in the
      food chain and in human blood and milk. Exposure to PCBs during pregnancy and
      lactation leads to cognitive impairment in children. The underlying mechanisms
      remain unclear. Some PCBs are endocrine disrupters. The aim of this work was to
      assess whether exposure of rats to PCB126 (dioxin-like) or PCB153 (non-dioxin
      like) during pregnancy and lactation affects the ability of the pups to learn a Y
      maze conditional discrimination task and/or the function of the glutamate-nitric
      oxide (NO)-cGMP pathway in brain in vivo when the rats are young (3 months) or
      adult (7-8 months). After finishing the learning experiments, the function of the
      pathway was analysed in the same rats by in vivo brain microdialysis. The results
      obtained show that perinatal exposure to PCB153 or PCB126: (1) impairs learning
      ability in young but not in adult rats, (2) impairs the glutamate-NO-cGMP pathway
      function in cerebellum in vivo in young but not in adult rats and (3) affect
      these parameters in males and females similarly. PCB126 is around 10 000-fold
      more potent than PCB153. In control rats the function of the glutamate-NO-cGMP
      pathway and learning ability are lower in adult than in young rats. These age
      related differences are not present in rats exposed to PCBs. The impairment of
      the glutamate-NO-cGMP pathway function induced at young age by developmental
      exposure to the PCBs could be one of the mechanisms contributing to the cognitive
      impairment found in children whose mothers ingested PCB-contaminated food during
      pregnancy and lactation.

PMID- 18093178
TI  - Exercise normalizes levels of MAG and Nogo-A growth inhibitors after brain
      trauma.
AB  - Myelin is a major obstacle for axonal growth after CNS injury, to the extent that
      it is crucial to develop interventions to counteract postinjury growth inhibition
      and foster neural repair. We have studied the effects of the fluid percussion
      injury (FPI) model of traumatic brain injury (TBI) on protein levels of two
      myelin-associated molecules, myelin-associated glycoprotein (MAG) and Nogo-A, in
      the adult rat. We found that FPI elevated hippocampal levels of MAG and Nogo-A.
      Given the beneficial effects of exercise on CNS function, we evaluated the
      capacity of exercise to reduce these myelin-derived proteins after FPI. One week
      of voluntary running wheel exercise overcame the injury-related increase in MAG
      and Nogo-A. The action of brain-derived neurotrophic factor (BDNF) has been
      associated with exercise as well as with the modulation of growth inhibition in
      vitro. We found that the selective blockade of BDNF using the immunoadhesive
      chimera TrkB-IgG abolished the effects of exercise on MAG and Nogo-A. FPI reduced
      levels of growth-associated protein 43 (GAP-43), a marker of axonal growth, and
      synaptophysin (SYP), an indicator of synaptic growth. Exercise counteracted the
      effects of FPI on GAP-43 and SYP, while BDNF blockade abolished these effects of
      exercise. 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 prevented by BDNF blockade. These results indicate
      that exercise promotes a permissive cellular environment for repair after TBI, in
      a process in which BDNF plays a central role.

PMID- 18093179
TI  - Insulin and IGF-1 enhance the expression of the neuronal monocarboxylate
      transporter MCT2 by translational activation via stimulation of the
      phosphoinositide 3-kinase-Akt-mammalian target of rapamycin pathway.
AB  - MCT2 is the main neuronal monocarboxylate transporter essential for facilitating
      lactate and ketone body utilization as energy substrates. Our study reveals that
      treatment of cultured cortical neurons with insulin and IGF-1 led to a striking
      enhancement of MCT2 immunoreactivity in a time- and concentration-dependent
      manner. Surprisingly, neither insulin nor IGF-1 affected MCT2 mRNA expression,
      suggesting that regulation of MCT2 protein expression occurs at the translational
      rather than the transcriptional level. Investigation of the putative signalling
      pathways leading to translation activation revealed that insulin and IGF-1
      induced p44- and p42 MAPK, Akt and mTOR phosphorylation. S6 ribosomal protein, a
      component of the translational machinery, was also strongly activated by insulin
      and IGF-1. Phosphorylation of p44- and p42 MAPK was blocked by the MEK inhibitor
      PD98058, while Akt phosphorylation was abolished by the PI3K inhibitor LY294002.
      Phosphorylation of mTOR and S6 was blocked by the mTOR inhibitor rapamycin. In
      parallel, it was observed that LY294002 and rapamycin almost completely blocked
      the effects of insulin and IGF-1 on MCT2 protein expression, whereas PD98059 and
      SB202190 (a p38K inhibitor) had no effect on insulin-induced MCT2 expression and
      only a slight effect on IGF-1-induced MCT2 expression. At the subcellular level,
      a significant increase in MCT2 protein expression within an intracellular pool
      was observed while no change at the cell surface was apparent. As insulin and IGF
      1 are involved in synaptic plasticity, their effect on MCT2 protein expression
      via an activation of the PI3K-Akt-mTOR-S6K pathway might contribute to the
      preparation of neurons for enhanced use of nonglucose energy substrates following
      altered synaptic efficacy.

PMID- 18093180
TI  - Killer cell immunoglobulin-like receptors on NK cells: the how, where and why.
AB  - Natural killer (NK) cells have killer cell immunoglobulin-like receptors (KIR)
      that recognize and interact with HLA class I antigen. The KIRs are a multigene
      family and its members are often highly polymorphic. Evidence is emerging from
      disease-association studies that KIR receptors can play beneficial roles in viral
      infections, such as HIV, HCV, but may also predispose to certain autoimmune
      diseases. Knowledge regarding expression and function of KIR on human NK cells is
      lagging behind the rapid expansion of sequencing and genetic data already
      generated. This review focuses on recent discoveries that have been made, which
      help bridge this gap. We now appreciate the importance of phenotypic diversity of
      KIR receptor expression in NK cells and are starting to unravel some of the
      mysteries surrounding control of their complex expression patterns. In
      particular, the role that HLA ligand contributes to KIR receptor expression will
      be discussed. It is also becoming increasingly clear that genetic factors, such
      as promoters and epi-genetic mechanisms such as methylation, are hugely important
      in controlling NK cell receptor expression and function. The relevance of
      phenotypic diversity of NK cell receptors will be discussed in light of these
      recent findings.

PMID- 18093181
TI  - Promoter polymorphism of the IL-18 gene is associated with atopic asthma in
      Tunisian children.
AB  - Several lines of evidence point to a relevant role of IL-18 in the process of
      asthma. Some studies suggest that the polymorphism in the gene of IL-18 can be
      involved in many inflammatory and atopic diseases such as asthma. The aim of our
      study is to estimate the frequency of the IL-18-607 C/A (rs 1946518) promoter
      polymorphism in Tunisian children with asthma. We investigated whether the
      presence of this polymorphism -607 C/A was associated with asthma or atopy and
      whether this polymorphism influenced the severity of asthma in affected children.
      We examined also the relationship between the IL-18 gene polymorphism and the
      serum total IgE level. The IL-18/-607 C/A polymorphism was analysed by polymerase
      chain reaction and restriction fragment-length polymorphism (PCR-RFLP) analysis.
      A total of 105 asthma patients and 112 controls as part of the whole children
      population were studied in a case-control study. Among the 105 children with
      asthma, 40 were also studied for linkage analyses with their respective parents.
      We noted that the A allele was associated with statistically significant
      increases in the risk of asthma in the case-control study (odd ratio (OR) = 1.55,
      95% confidence interval (CI) 1.03-2.33. Moreover, the A allele was also
      associated with atopic asthma (P = 0.008), but not with asthma severity. The
      transmission disequilibrium test (TDT) analysis in this family study did not
      suggest a preferential transmission of the IL-18/ -607 C/A polymorphism to
      affected children. There is no correlation between the IgE level and the IL-18 
      607 C/A promoter polymorphism. Our data indicate that IL-18 -607 C/A promoter
      polymorphism is associated with susceptibility to developing asthma in Tunisian
      population.

PMID- 18093182
TI  - Distribution of the CTLA-4 single nucleotide polymorphisms CT60G>A and +49A>G in
      psoriasis vulgaris patients and control individuals from a Polish Caucasian
      population.
AB  - Psoriasis vulgaris is a multifactorial disease with an autoimmune component, and
      T lymphocytes seem to be involved in its aetiology. CTLA-4 molecule is an
      important down-regulator of T-lymphocyte activation, and several polymorphisms of
      the CTLA-4 gene were found to be associated with some autoimmune diseases. We
      examined whether single nucleotide polymorphisms (SNPs) in the CTLA-4 gene,
      CT60A>G and +49A>G, are associated with psoriasis vulgaris. Alleles of these two
      SNPs were determined by the polymerase chain reaction-restriction fragment length
      polymorphism method. Both the CT60G>A and the +49A>G alleles and genotypes were
      distributed similarly in patients and controls. Although the two SNPs studied
      here in Poles were in linkage disequilibrium, all four possible two-locus
      haplotypes were found, one of them rare; of the remaining three, the haplotype
      +49G, CT60G was significantly (P = 0.019, OR = 0.58, 95%CI = 0.37-0.91) less
      frequent in the patient group with disease onset between the ages of 21 and 40
      years than in controls and the other patient groups, whereas the frequencies of
      the other haplotypes were similar in patients and controls. To the authors'
      knowledge, this is the first study on CTLA-4 CT60 allele frequencies in
      psoriasis.

PMID- 18093183
TI  - A functional promoter polymorphism in monocyte chemoattractant protein-1 is
      associated with psoriasis.
AB  - Psoriasis is one of the most common inflammatory diseases of skin. MCP-1 is an
      important CC-type chemokine responsible for monocytes and T lymphocytes
      recruitment in inflammatory conditions. A single nucleotide polymorphism of the
      MCP-1 gene in the gene regulatory region was found to be related to the
      expression of MCP-1, and the associations of this polymorphism with many
      inflammatory diseases were conformed. However, the significance of this
      polymorphism in psoriasis remains unclear. Therefore, we examined this
      polymorphism in 507 patients with plaque-type psoriasis and 530 healthy controls
      using the polymerase chain reaction-restriction fragment length polymorphism
      method. We also tested the serum MCP-1 in 320 patients and 160 controls and
      compared the serum MCP-1 level in patients of different genotypes. Our results
      showed that the frequency distribution of the AA, AG and GG genotypes between the
      patients and the controls was statistically different (P = 0.031); significantly
      increased risk for psoriasis was associated with the AG, GG and AG + GG genotype.
      The frequency distribution of the AA, AG and GG genotypes was also different
      between female psoriasis patients and controls (P = 0.025), between type I
      psoriasis patients and controls (P = 0.025), between psoriasis patients without
      positive familial history and controls (P = 0.048), and between patients with
      psoriasis area and severity index of > or = 10 and controls (P = 0.041). MCP-1
      serum level was significantly higher in patients than controls (P < 0.0001).
      There were significant differences of serum MCP-1 level between patients of the
      GG genotype and the AA genotype (P = 0.028), between patients of the AG genotype
      and the AA genotype (P = 0.049), and between patients of the AG + GG genotype and
      the AA genotype (P = 0.027). These results showed the -2518 MCP-1 polymorphism is
      related to the susceptibility of plaque type psoriasis. Individuals containing
      the GG or AG genotype were at higher risk of psoriasis than subjects with the AA
      genotype.

PMID- 18093184
TI  - Activated Rac1, but not the tumorigenic variant Rac1b, is ubiquitinated on Lys
      147 through a JNK-regulated process.
AB  - Ubiquitination and proteasomal degradation have recently emerged as an additional
      level of regulation of activated forms of Rho GTPases. To characterize this novel
      regulatory pathway and to gain insight into its biological significance, we
      studied the ubiquitination of two constitutively activated forms of Rac1, i.e.
      the mutationally activated Rac1L61, and the tumorigenic splice variant Rac1b,
      which is defective for several downstream signaling pathways, including JNK
      activation. Whereas Rac1L61 undergoes polyubiquitination and subsequent
      proteasomal degradation in HEK293 cells, Rac1b is poorly ubiquitinated and
      appears to be much more resistant to proteasomal degradation than Rac1L61.
      Mutational analysis of all lysine residues in Rac1 revealed that the major target
      site for Rac1 ubiquitination is Lys147, a solvent-accessible residue that has a
      similar conformation in Rac1b. Like Rac1L61, Rac1b was found to be largely
      associated with plasma membrane, a known prerequisite for Rac1 ubiquitination.
      Interestingly, Rac1b ubiquitination could be stimulated by coexpression of
      Rac1L61, suggesting positive regulation of Rac1 ubiquitination by Rac1 downstream
      signaling. Indeed, ubiquitination of Rac1L61 is critically dependent on JNK
      activation. IN CONCLUSION: (a) Rac1b appears to be more stable than Rac1L61 with
      regard to the ubiquitin-proteasome system, and this may be of importance for the
      expression and tumorigenic capacity of Rac1b; and (b) ubiquitination of activated
      Rac1 occurs through a JNK-activated process, which may explain the defective
      ubiquitination of Rac1b. The JNK-dependent activation of Rac1 ubiquitination
      would create a regulatory loop allowing the cell to counteract excessive
      activation of Rac1 GTPase.

PMID- 18093185
TI  - Lumican expression is positively correlated with the differentiation and
      negatively with the growth of human osteosarcoma cells.
AB  - Osteosarcoma is the most common primary bone tumour associated with childhood and
      adolescence. The possible role of the small leucine-rich proteoglycan, lumican,
      in the growth and metastasis of various cancer types has recently been
      investigated. In this study, the expression of lumican was examined in moderately
      differentiated (MG-63) and well-differentiated (Saos 2) human osteosarcoma cell
      lines of high and low metastatic capability, respectively. Real-time PCR, western
      blotting with antibodies against the protein core and keratan sulfate, and
      specific enzymatic digestions were the methods employed. The two human
      osteosarcoma cell lines were found to express and secrete lumican partly
      substituted with keratan sulfate glycosaminoglycans. Importantly, the non
      metastatic, well-differentiated Saos 2 cells produced lumican at rates that were
      up to sevenfold higher than those of highly metastatic MG-63 cells. The
      utilization of short interfering RNA specific for the lumican gene resulted in
      efficient down-regulation of its mRNA levels in both cell lines. The growth of
      Saos 2 cells was inhibited by lumican, whereas their migration and chemotactic
      response to fibronectin were found to be promoted. Lumican expression was
      negatively correlated with the basal level of Smad 2 activation in these cells,
      suggesting that lumican may affect the bioavailability of Smad 2 activators. By
      contrast, these cellular functions of highly aggressive MG-63 cells were
      demonstrated not to be sensitive to a decrease in their low endogenous lumican
      levels. These results suggest that lumican expression may be positively
      correlated with the differentiation and negatively correlated with the
      progression of osteosarcoma.

PMID- 18093186
TI  - Transient buccal nerve paresis.

PMID- 18093187
TI  - Extraocular sebaceous carcinoma treated with Mohs micrographic surgery: report of
      a case and review of literature.

PMID- 18093188
TI  - Hemorrhagic foreign body granuloma after cutaneous surgery occurring in the
      setting of aspirin therapy or thrombocytopenia: a presentation of six cases.

PMID- 18093189
TI  - Surgical glue to secure small split-thickness skin grafts: a cost-effective and
      time-saving technique.

PMID- 18093190
TI  - Modification of the purse-string closure for large defects of the extremities.

PMID- 18093191
TI  - How to avoid eyebrow pull-up in forehead reconstruction.

PMID- 18093192
TI  - Repair of a large, exposed-cartilage nasal tip defect using nasalis-based
      subcutaneous pedicle flaps and full-thickness skin grafting.

PMID- 18093195
TI  - The Peng flap: reviewed and refined.
AB  - BACKGROUND: The Peng flap was first described in 1987 and there has been only one
      subsequent article published about its use. The Peng flap is very versatile and
      has a greater range of application than previously described. It can be used for
      central and eccentric defects of the nasal tip and it is also an excellent choice
      for defects that bridge the proximal nasal tip with the distal dorsum. OBJECTIVE:
      In this series, we present several new modifications to the Peng flap. METHODS:
      We describe conceptual changes in the movement dynamics of the flap based on
      these design refinements. Additional detail regarding flap execution is provided.
      RESULTS: Presented here is retrospective data on the last 30 patients from our
      tumor registry who received Peng flap repairs between 2001 and 2006. The average
      defect size was 1.8 x 1.5 cm. CONCLUSIONS: Described herein is a refined flap
      design that: (1) hides incisions in cosmetic junctions, (2) achieves a wider
      pedicle, and (3) utilizes a larger component of cheek advancement than previously
      described.

PMID- 18093196
TI  - Hidradenitis suppurativa: importance of early treatment; efficient treatment with
      electrosurgery.
AB  - BACKGROUND: Hidradenitis suppurativa is a challenging condition, both for the
      physicians and for the patients. Many surgical and medical approaches with
      different success rates have been undertaken. Early and appropriate intervention
      is a factor that significantly increases the success rate of the treatment of the
      disease. OBJECTIVE: This study was conducted to evaluate the efficiency of
      electrosurgery treatment in early hidradenitis suppurativa. MATERIALS AND
      METHODS: This study comprised 12 patients aged between 29 and 38 years (mean, 34
      years) with a diagnosis of hidradenitis suppurativa Grade I (n=9) or Grade II
      (n=3). A surgical method consisted of excision of the areas with nodules and
      sinuses, up to the level of subcutaneous fat tissue, and leaving the surgical
      defect for secondary healing. RESULTS: All patients completed the study. In 10 of
      12 (83%) patients, 26 of 30 (86%) lesions, cure was observed in a mean of 16 days
      (range 15 to 21 days). Four lesions in 2 patients with Grade II became infected
      and required a short course of antibiotic therapy. CONCLUSION: Electrosurgery
      will decrease the need for other systemic treatments, owing to its high cure
      rates. Our results showed that electrosurgery should be considered a top
      alternative in the treatment algorithm of hidradenitis suppurativa.

PMID- 18093197
TI  - Surgical treatment of hidradenitis suppurativa with gentamicin sulfate: a
      prospective randomized study.
AB  - BACKGROUND AND METHOD: This article describes and discusses a prospective
      randomized study with gentamicin sulfate in the surgical treatment of
      hidradenitis suppurativa. The purpose of the study was to investigate whether
      enclosure of antibiotics after primary excision and closure reduces the number of
      postoperative infections. Therefore, the hidradenitis lesions were excised and
      closed with or without enclosure of a gentamicin-collagen sponge (GC). RESULTS: A
      total of 200 patients were included in the study. Seventy-six patients underwent
      surgical excision with primary closure (PC), and 124 PCs over a GC. After 1 week
      there were significantly fewer complications (infection, dehiscence, etc.) in the
      GC group, 35% versus 52%; after 3 months the complications in both groups were
      comparable, 12% versus 19% (Table 2). The mean period of wound healing was 21
      days in the first group and 24 days in the second group. The recurrence rate
      after 3 months was comparable in both groups, 40% versus 42%. CONCLUSION: This
      study shows that enclosure of gentamicin after primary excision of hidradenitis
      suppurativa reduces the number of complications 1 week postoperatively.
      Furthermore, in 65% of the patients treated with gentamicin, the wound was
      completely healed within 2 months. There is no effect on the long term recurrence
      rate, as expected.

PMID- 18093198
TI  - The effects of sirolimus on wound healing in dermatologic surgery.
AB  - BACKGROUND: Sirolimus, a TOR (target of rapamycin)-binding immunosuppressant, has
      been associated with wound healing complications; however, its effects have not
      been documented in dermatologic surgery. OBJECTIVE: The objective was to
      determine the effect of sirolimus on wound healing in dermatologic surgery.
      METHODS AND MATERIALS: Databases at Mayo Clinic were queried for organ transplant
      recipients undergoing dermatologic surgery. Medical records were reviewed
      retrospectively, and telephone interviews were conducted. Patients receiving
      sirolimus were compared with patients not receiving sirolimus. RESULTS:
      Postoperative infections occurred in 19.2% of the sirolimus group (n=26) and 5.4%
      of the controls (n=37; p=.11; odds ratio [OR], 4.2; 95% confidence interval [CI],
      0.7-23.4). The incidence of wound dehiscence was greater in the sirolimus group
      (7.7% vs. 0%; p=.17; OR, 7.7; 95% CI, 0.4-166.3). CONCLUSION: No significantly
      increased risk of wound complications was found in organ transplant recipients
      receiving sirolimus while undergoing dermatologic surgery. However, this study
      was retrospective and had a small sample size. A larger study is necessary for
      corroboration.

PMID- 18093199
TI  - Calcium hydroxylapatite versus nonanimal stabilized hyaluronic acid for the
      correction of nasolabial folds: a 12-month, multicenter, prospective, randomized,
      controlled, split-face trial.
AB  - BACKGROUND: Fillers continue to proliferate in dermatology. Rigorous clinical
      trials can help determine the advantages and disadvantages of these products as
      they come to market. OBJECTIVE: This randomized, split-face, controlled study
      compared the efficacy, safety, durability, and volumes of calcium hydroxylapatite
      (CaHA) versus nonanimal-stabilized hyaluronic acid (NASHA) in nasolabial folds.
      METHODS AND MATERIALS: Sixty patients were enrolled at two medical clinics in
      Europe (Summer 2005). Patients received two injections 3 months apart. Patients
      returned at 6, 9, and 12 months for a blinded evaluation, using accepted
      aesthetic rating scales. Adverse events were recorded throughout the study.
      RESULTS: At all time points, CaHA was found to be more effective than NASHA. At
      12 months, 79% of CaHA folds were still improved or better versus 43% of NASHA
      folds (p<.0001). In addition, 30% less total CaHA volume was required compared to
      NASHA. Evaluators assessed CaHA as superior in 47% of patients and inferior in
      only 5% (p<.0001). Blinded evaluators and patients preferred CaHA two to one
      (p<.05). Both products were safe and well tolerated. CONCLUSION: CaHA was found
      to be significantly more effective than NASHA. At all time points, CaHA
      demonstrated longer lasting results and greater improvement than NASHA.

PMID- 18093200
TI  - Clinical, laboratory, and MRI analysis of cellulite treatment with a unipolar
      radiofrequency device.
AB  - BACKGROUND: Cellulite is seen in more than 85% of postpubertal women. Recent
      studies show that bipolar radiofrequency and low-level laser devices can produce
      mild skin tightening of cellulite. OBJECTIVE: The primary objective was to
      determine if a novel unipolar, more deeply penetrating, radiofrequency device can
      promote better skin tightening with fewer treatments than is seen with previously
      described devices. The secondary objective was to determine if such a deeply
      penetrating device produced undesired effects on lipid metabolism. METHODS:
      Thirty subjects, with Nurnberger-Muller Scale III-IV upper thigh cellulite, were
      entered into the study. All were treated, every other week, with a unipolar
      radiofrequency device for a total of six treatments. Subjects were evaluated
      before and 6 months after treatment with clinical photographs, clinical
      measurements, biopsies, MRIs, and blood lipid evaluations. RESULTS: Twenty-seven
      subjects showed evidence of clinical improvement. The mean decrease in leg
      circumference was 2.45 cm. Histologic changes showed dermal fibrosis of the upper
      dermis. No MRI or lipid abnormalities were noted. CONCLUSION: Upper thigh skin
      cellulite can be improved with a new unipolar radiofrequency device. Histologic
      changes suggest skin tightening as the method of improvement. No undesired
      complications of the skin or lipid metabolism were noted.

PMID- 18093201
TI  - Review of 1,000 consecutive short-scar rhytidectomies.
AB  - BACKGROUND: Short-scar rhytidectomies offer patients with mild to moderate facial
      aging an alternative to traditional face-lift surgery. Advantages of decreased
      recovery time, diminished risk, and decreased cost make this an attractive
      procedure to add to a cosmetic surgery practice. METHODS: This study is a review
      of 1,000 consecutive short-scar rhytidectomies performed over 36 months with at
      least 6 months of follow-up. All patients underwent short-scar rhytidectomy with
      SMAS suspension. Outcome parameters examined included complications or adverse
      events and any interventions necessary. RESULTS: The most common complication was
      suture extrusion, observed in 148 patients (14.8%). Ten patients had hematomas
      (1%), while postauricular nodules were observed in 8 patients (0.8%). Eight
      patients (0.8%) required liposuction under local anesthesia to address asymmetry
      due to under removal of fat in the submental region. Revision rhytidectomy was
      required in 5 patients (0.5%). Five patients (0.5%) had hypertrophic scarring,
      while 1 patient (0.1%) developed hyperpigmentation. There were no cases of nerve
      injury, infection, skin flap necrosis, skin puckering or depression, hair loss,
      or parotid injury. CONCLUSION: Short-scar rhytidectomy is an excellent procedure
      for good candidates with mild to moderate aging of the face. It has a very low
      complication rate and can be done safely in an office environment.

PMID- 18093202
TI  - Cutaneous compression for the laser treatment of epidermal pigmented lesions with
      the 595-nm pulsed dye laser.
AB  - BACKGROUND: The 595-nm pulsed dye laser has been the standard of care for many
      vascular lesions and has rarely been used in the treatment of epidermal pigmented
      lesions. OBJECTIVE: The objective was to investigate the effectiveness and safety
      of a compression technique for the treatment of epidermal pigmented lesion using
      a modified 595-nm pulsed dye laser with no epidermal cooling. METHODS: Twelve
      subjects (mean age 58 years) underwent treatments using a modified 595-nm dye
      laser with a compression handpiece and no epidermal cooling. Treatments were
      performed with radiant exposures of 7 to 12 J/cm(2), 7-mm spot size, and 1.5-ms
      pulse duration. Each subject received one to four treatments, 4 to 6 weeks apart.
      Follow-up evaluations were held before each treatment and 4 months after last
      treatment. RESULTS: Clearance of 75% to 100% was obtained in 43, 59, 76, and 79%
      of the lesions treated after one, two, three, and four treatments respectively.
      The fourth treatment was evaluated 4 months posttreatment. Side effects included
      immediate erythema and edema and rare cases of transient hyperpigmentation and
      atrophy. No purpura and long-lasting side effects were observed. CONCLUSION: The
      compression technique with a modified 595-nm pulsed dye laser system is effective
      and safe for the treatment of epidermal pigmented lesions.

PMID- 18093203
TI  - Punch grafting versus suction blister epidermal grafting in the treatment of
      stable lip vitiligo.
AB  - BACKGROUND: Among surgical methods, punch skin grafting (PSG) and suction blister
      epidermal grafting (SBEG) are simple, inexpensive, and effective treatment
      methods for resistant lip vitiligo cases, but there is a lack of comparison
      between these procedures for lip vitiligo. OBJECTIVE: The objective was to
      compare the outcome following PSG and SBEG in stable lip vitiligo. METHODS:
      Eighteen patients with stable lip vitiligo were randomly selected. Eight patients
      were included in PSG group and 10 patients in SBEG. All patients were kept on
      PUVA-SOL (psoralen+ultraviolet A therapy of solar origin) treatment after
      grafting. The results were evaluated after a follow-up period of 6 months.
      RESULTS: At the end of 6 months of grafting in PSG group, two patients had a
      repigmentation of 50% to 75%, one had 75% to 90%, and three had 90% to 100% in
      the recipient site in lip. In SBEG group, one patient had repigmentation of 50%
      to 75%, three had 75% to 90%, and two had 90% to 100%. The color match was
      statistically significant in PSG when compared to SBEG. In the recipient site,
      cobblestone appearance was the predominant complication in PSG whereas
      hyperpigmentation and thickening of grafts were common in SBEG. In the donor
      site, superficial scarring and hypopigmentation were the common findings in PSG
      group whereas hyperpigmentation was the main problem in SBEG group. CONCLUSIONS:
      Although both the procedures are effective in lip vitiligo, PSG gives a better
      color match than SBEG.

PMID- 18093204
TI  - A meta-analysis of complications attributed to anticoagulation among patients
      following cutaneous surgery.
AB  - BACKGROUND: The frequency of postoperative bleeding and other complications in
      anticoagulated patients undergoing cutaneous surgery has not been firmly
      established and consensus on perioperative continuation of treatment is lacking.
      OBJECTIVE: The objective was to ascertain the risk of postoperative complications
      through meta-analysis of data pooled from previously published studies. METHODS:
      A PubMed search (1966-2005) was performed to identify controlled studies
      reporting bleeding and other complications among patients undergoing cutaneous
      surgery who were taking anticoagulant medications. Emphasis was placed on
      prescription anticoagulant medications (aspirin, NSAIDs, warfarin, clopidogrel)
      and over-the-counter herbal agents with anticoagulant properties. RESULTS: A
      total of six studies representing 1,373 patients met criteria for inclusion.
      Among patients taking aspirin or warfarin, 1.3 and 5.7% experienced a severe
      postoperative complication, respectively. Patients taking warfarin were nearly
      seven times as likely to have a moderate-to-severe complication compared to
      controls (OR, 6.69; 95% CI, 3.03-14.7), a statistically significant difference
      (p<.001). Patients taking aspirin or NSAIDs were more than twice as likely to
      have a moderate-to-severe complication compared to controls (OR, 2.0; 95% CI,
      0.97-4.13), a strong trend toward statistical significance (p=.06). There were no
      studies in the literature that examined the effects of combination anticoagulant
      therapy or the effect of herbal agents on postoperative risk of bleeding.
      CONCLUSION: The results of this meta-analysis suggest that while low, the risk of
      bleeding among anticoagulated patients may be higher than baseline. Adequately
      powered prospective studies are required to more carefully delineate the risk of
      postoperative bleeding and other complications attributable to anticoagulation
      therapy. Particular emphasis should be placed on examining the effect of
      combination anticoagulant therapy as well as herbal agents with anticoagulant
      properties on risk of bleeding after cutaneous surgery.

PMID- 18093205
TI  - Trends in pediatric melanoma mortality in the United States, 1968 through 2004.
AB  - BACKGROUND AND OBJECTIVE: Mortality from melanoma in children is a poorly
      understood and controversial problem in dermatology. There is paucity of research
      into this important public health dilemma. The purpose of this study was to
      characterize pediatric melanoma mortality in the United States and to evaluate
      trends over time. METHODS AND MATERIALS: Deaths were derived from a database of
      more than 75 million records of the U.S. Center for National Health Statistics
      based on routine death certification. Information on age, race, gender, and
      geographic location was available for years 1968 through 2004. RESULTS: During
      the 37-year period, there were 643 deaths attributed to melanoma in children
      under 20 years of age in the United States, an average of 18 per year. The
      overall age-adjusted mortality rate for melanoma in children was 2.25 deaths per
      year (per 10 million at-risk individuals). Mortality rates were strongly
      associated with age. In the oldest age group (age 15-19 years) the mortality rate
      was approximately an order of magnitude 8-18 times higher compared to younger age
      groups. Mortality among males was 25% higher than females. Mortality rates for
      white children were more than twice as high as black children. Overall mortality
      from melanoma in children declined steadily from 1968 to 2004. The highest
      mortality rates were observed in Idaho, Nevada, Arizona, and New Mexico.
      CONCLUSIONS: Although mortality from melanoma among children in the United State
      is low, the magnitude of the public health burden from this preventable cause of
      death is substantial. In contrast to results of studies suggesting that the
      incidence of melanoma may be rising in children and adolescents, the data suggest
      that mortality in these groups may be falling. Additional study is warranted to
      further characterize and ultimately reduce mortality from childhood melanoma.

PMID- 18093206
TI  - Treatment of lentigo maligna with imiquimod before staged excision.
AB  - BACKGROUND: Imiquimod 5% cream has demonstrated effectiveness in the treatment of
      lentigo maligna (LM) in several small studies. None of the studies to date have
      included posttreatment surgical removal to confirm negative histologic margins.
      OBJECTIVE: The aim of this retrospective analysis was to assess the efficacy of
      topical imiquimod in LM by circumferentially examining vertically oriented
      sections from a geometrically designed "picture frame" margin as well as bread
      loafed sections of the central portion after staged excisions of imiquimod
      treated lesions of LM. METHODS: Forty patients with biopsy-confirmed LM were
      treated five times a week for 3 months with 5% imiquimod cream before staged
      excision. Tazarotene 0.1% gel was added when no clinical signs of erythema
      developed with imiquimod alone after 1 month (10 patients). After the course of
      topical therapy, patients were assessed for clinical and complete histologic
      clearance after staged excision. RESULTS: A total of 33 of 40 patients had a
      complete clinical response as determined by the absence of remaining clinical
      lesion on physical examination. Upon histologic review, 30 of 40 patients had no
      evidence of LM whereas 10 of 40 harbored residual disease. One patient was found
      to have histologic evidence of invasion after completing the topical protocol.
      After a mean follow-up of 18 months (range, 12-34 months) and after complete
      surgical excision of the treatment site, none of the imiquimod-treated patients
      had evidence of recurrence. CONCLUSIONS: Imiquimod appears to be an effective
      adjunctive treatment for LM but does not qualify as a replacement therapy for
      surgery.

PMID- 18093207
TI  - Robust improvements in fasting and prandial measures of beta-cell function with
      vildagliptin in drug-naive patients: analysis of pooled vildagliptin monotherapy
      database.
AB  - AIM: To assess the effects of 24-week treatment with vildagliptin on measures of
      beta-cell function in a broad spectrum of drug-naive patients with type 2
      diabetes (T2DM). METHODS: Data from all double-blind, multicentre, randomized,
      placebo- or active-controlled trials conducted in drug-naive patients with T2DM
      were pooled from all patients receiving monotherapy with vildagliptin (100 mg
      daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347).
      Fasting measures of beta-cell function [homeostasis model assessment of beta-cell
      function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall
      pooled monotherapy population. Standard meal tests were performed at baseline and
      week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n =
      227) on dynamic (meal test-derived) measures of beta-cell function [insulin
      secretion rate relative to glucose (ISR/G) and insulinogenic indices] were
      assessed relative to baseline and vs. placebo (n = 29). RESULTS: In the overall
      population, vildagliptin significantly increased HOMA-B both relative to baseline
      [adjusted mean change (AMDelta) = 10.3 +/- 1.5] and vs. placebo (between
      treatment difference in AMDelta = 11.5 +/- 4.5, p = 0.01) and significantly
      decreased the proinsulin : insulin ratio relative to baseline (AMDelta = -0.05 +/
      0.01) and vs. placebo (between-treatment difference in AMDelta = -0.09 +/- 0.02,
      p < 0.001). Relative to baseline, vildagliptin monotherapy significantly
      increased all meal test-derived parameters, and ISR/G (between-treatment
      difference in AMDelta = 9.8 +/- 2.8 pmol/min/m(2)/mM, p < 0.001) and the
      insulinogenic index(0-peak glucose) (between-treatment difference in AMDelta =
      0.24 +/- 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo.
      CONCLUSIONS: Vildagliptin monotherapy consistently produced robust improvements
      in both fasting and meal test-derived measures of beta-cell function across a
      broad spectrum of drug-naive patients with T2DM. All Phase III trials described
      (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT
      00120536) are registered with ClinicalTrials.gov.

PMID- 18093208
TI  - No differences in mortality between users of pancreatic-specific and non
      pancreatic-specific sulphonylureas: a cohort analysis.
AB  - To assess whether users of pancreatic-specific sulphonylureas are at reduced risk
      of mortality and cardiovascular mortality compared with users of non-specific
      sulphonylureas, we conducted a cohort study in the population of Tayside,
      Scotland. We identified 3331 patients with type 2 diabetes who were newly treated
      with sulphonylureas between 1994 and 2001 and categorized them into those treated
      with only pancreatic-specific sulphonylureas and those treated with only non
      specific sulphonylureas. The risks of mortality and cardiovascular mortality were
      compared in a survival analysis. There were 2914 patients treated with pancreatic
      specific sulphonylureas only, of which 683 (23.4%) died. Of 186 patients treated
      with non-specific drugs only, 40 (21.5%) died. After adjusting for confounding
      factors, the adjusted risk ratios (with 95% CI) for mortality and cardiovascular
      mortality were 0.84 (0.61 to 1.17) and 0.81 (0.59 to 1.11) among the non-specific
      users compared with the pancreatic-specific users. This provides no evidence that
      there are differences between the two sulphonylureas types.

PMID- 18093209
TI  - Exenatide prevents fat-induced insulin resistance and raises adiponectin
      expression and plasma levels.
AB  - BACKGROUND: Exenatide (exendin-4) can reduce blood glucose levels, increase
      insulin secretion and improve insulin sensitivity through mechanisms that are not
      completely understood. METHODS: In the present study, we examined the effects of
      exenatide treatment on glucose tolerance (intravenous glucose tolerance test),
      insulin sensitivity (euglycaemic-hyperinsulinaemic clamps), insulin signalling
      (insulin receptor substrate 1 tyrosine phosphorylation) and adipocytokine levels
      (visfatin and adiponectin) in high fat-fed rats. RESULTS: Administration of
      exenatide (0.5 or 2.0 mug/kg twice daily x 6 weeks) prevented high-fat diet (HFD)
      induced increases in body weight, plasma free fatty acids, triglycerides and
      total cholesterol. Exenatide also prevented HFD-induced deterioration in
      peripheral and hepatic insulin sensitivity, insulin clearance, glucose tolerance
      and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in
      fat and skeletal muscles. Interestingly, plasma visfatin levels decreased in
      exenatide-treated rats, whereas expression and plasma levels of adiponectin
      increased. CONCLUSIONS: These results indicate that chronic exenatide treatment
      enhances insulin sensitivity and protects against high fat-induced insulin
      resistance.

PMID- 18093210
TI  - Anaemia in diabetic renal failure: is there a role for early erythropoietin
      treatment in preventing cardiovascular mortality?
AB  - The mortality rate in diabetics with chronic kidney disease (CKD) is seven times
      higher than end-stage renal disease mainly because of cardiac causes. Anaemia may
      have a relevant role in the pathogenesis of cardiovascular (CV) disease in CKD.
      Anaemia occurs at an earlier stage of CKD in diabetic individuals than in those
      with other causes of CKD. Observational findings support the unfavourable
      influence of anaemia on mortality in CKD patients, and the combination of anaemia
      and CKD in diabetics identifies a group with a particularly high mortality risk.
      While the effect of erythropoietin on these patients' quality of life is known,
      its impact on mortality and CV risk is uncertain. The recent Anaemia Correction
      in Diabetes (ACORD) trial in diabetic CKD patients, which targeted haemoglobin
      levels of 13-15 mg/dl, disclosed no statistically significant favourable or
      adverse effects on mortality or morbidity over the 2-year follow-up, while other
      studies endeavouring to nearly normalize haemoglobin have reportedly proved
      risky. Even if anaemia is causally involved, the pathogenesis of CV disease in
      diabetics with CKD is so complex that addressing just one factor (anaemia) may
      not suffice to prevent CV risk, and normalizing haemoglobin levels may even be
      harmful.

PMID- 18093211
TI  - Gender and neurogenin3 influence the pathogenesis of ketosis-prone diabetes.
AB  - Ketosis-prone diabetes (KPD) is a phenotypically defined form of diabetes
      characterized by male predominance and severe insulin deficiency. Neurogenin3
      (NGN3) is a proendocrine gene, which is essential for the fate of pancreatic beta
      cells. Mice lacking ngn3 develop early insulin-deficient diabetes. Thus, we
      hypothesized that gender and variants in NGN3 could predispose to KPD. We have
      studied clinical and metabolic parameters according to gender in patients with
      KPD (n = 152) and common type 2 diabetes (T2DM) (n = 167). We have sequenced NGN3
      in KPD patients and screened gene variants in T2DM and controls (n = 232). In
      KPD, male gender was associated with a more pronounced decrease in beta-cell
      insulin secretory reserve, assessed by fasting C-peptide [mean (ng/ml) +/- s.d.,
      M: 1.1 +/- 0.6, F: 1.5 +/- 0.9; p = 0.02] and glucagon-stimulated C-peptide [mean
      (ng/ml) +/- s.d., M: 2.2 +/- 1.1, F: 3.1 +/- 1.7; p = 0.03]. The rare affected
      females were in an anovulatory state. We found two new variants in the promoter [
      3812T/C (af: 2%) and -3642T/C (af: 1%)], two new coding variants [S171T (af: 1%)
      and A185S (af: 1%)] and the variant already described [S199F (af: 69%)]. These
      variants were not associated with diabetes. Clinical investigation revealed an
      association between 199F and hyperglycaemia assessed by glycated haemoglobin
      [HbA1c (%, +/-s.d.) S199: 12.6 +/- 1.6, S199F: 12.4 +/- 1.4 and 199F: 14.1 +/-
      2.2; p = 0.01]. In vitro, the P171T, A185S and S199F variants did not reveal
      major functional alteration in the activation of NGN3 target genes. In
      conclusion, male gender, anovulatory state in females and NGN3 variations may
      influence the pathogenesis of KPD in West Africans. This has therapeutic
      implications for potential tailored pharmacological intervention in this
      population.

PMID- 18093212
TI  - The effectiveness of glibenclamide in women with gestational diabetes.
AB  - BACKGROUND: Several studies have suggested that glibenclamide may be used safely
      and effectively in women with gestational diabetes mellitus (GDM). The aim of our
      study was to assess effectiveness and safety of glibenclamide for GDM in UK
      clinical practice. METHODS: Women with GDM requiring pharmacological therapy were
      offered a choice of insulin or glibenclamide. Maternal and foetal outcomes were
      assessed in women treated with insulin (45) or glibenclamide (44) and also
      compared with women treated with diet alone (55). RESULTS: Thirty-four (77%)
      achieved adequate glycaemic control with glibenclamide. Women choosing
      glibenclamide were more likely to be Asian and had higher fasting and 2-h glucose
      at diagnosis than those choosing insulin. There was no difference in maternal age
      or parity. Ten women treated with glibenclamide switched to insulin [inadequate
      control (7), unpredictable hypoglycaemia (1) and other reason (2)]. There was no
      difference in mode of birth, birth weight or birth weight centile between groups.
      One stillbirth occurred with glibenclamide. Glibenclamide treatment was
      associated with lower Apgar scores and increased neonatal jaundice. Neonatal
      hypoglycaemia occurred more frequently in babies of women treated with either
      glibenclamide or insulin. CONCLUSION: The use of glibenclamide in pregnancy is
      associated with adequate glycaemic control in 77% of women and achieved similar
      foetal outcomes to women treated with insulin.

PMID- 18093213
TI  - Preglomerular and postglomerular basal diameter changes and reactivity to
      angiotensin II in obese rats.
AB  - AIM AND METHODS: Obesity in humans is associated with proteinuria and an
      increased glomerular filtration, possibly related to an increase in glomerular
      capillary pressure. We investigated in obese and lean Zucker rats (10-12 weeks
      old) whether this might be related to alterations in the diameter of
      preglomerular and postglomerular microvessels and their reactivity to the
      resistance regulator angiotensin II (AngII), using the hydronephrotic kidney
      model. RESULTS: The obese rats exhibited a hyperinsulinaemic, euglycaemic state
      and hypertension. Urinary protein concentration and fluid intake were both
      increased threefold. Basal diameters of distal interlobular arteries (ILAs) and
      afferent arterioles (AAs) were larger in the obese rat than in the lean rat (ILA:
      25.7 +/- 0.3 vs. 23.0 +/- 0.4 microm and AA: 18.8 +/- 0.3 vs. 16.7 +/- 0.5
      microm, respectively; p </= 0.01), while diameters of efferent arterioles (EAs)
      were smaller in obese animals (14.2 +/- 1.1 vs. 18.2 +/- 1.2 microm; p </= 0.05).
      AngII induced a concentration-dependent constriction in ILA, AA and EA with an
      augmented response in the obese compared with the lean rats. Thus, at higher
      concentrations, AngII abolished the diameter difference between obese and lean
      animals in preglomerular microvessels while exaggerating that in postglomerular
      arterioles. CONCLUSIONS: Our data indicate that in obese rats, a vasodilated
      state in small preglomerular microvessels and a vasoconstricted state in the
      postglomerular arterioles exist. Although AngII cancelled the former, the latter
      remained. Therefore, these data reveal periglomerular vascular changes that may
      play a role in glomerular dysfunction and renal pathology associated with
      obesity.

PMID- 18093214
TI  - Renoprotective action of L-carnitine in fructose-induced metabolic syndrome.
AB  - AIM: Rats fed high dosage of fructose that form a well-known experimental model
      of the metabolic syndrome also display progressive renal disturbances. The
      present study evaluates the influence of l-carnitine (CA) administration on
      oxidant-antioxidant balance, protein damage and lipid levels in kidney of rats
      administered high dose of fructose. METHODS: Adult male Wistar rats were divided
      into four groups of 10 rats each. Groups I and IV animals received starch-based
      control diet, while groups II and III rats were fed a high-fructose diet (60
      g/100 g). Groups III and IV animals additionally received CA (300 mg/kg/day) for
      60 days. The extent of lipid peroxidation, enzymatic and non-enzymatic
      antioxidants and lipid levels were measured after 60 days. The accumulation of
      nitrated and oxidatively modified proteins in kidney was also measured by
      immunohistochemical study with specific antibodies. RESULTS: Fructose-fed rats
      exhibited increased levels of peroxidation end products, diminished antioxidant
      status, increased staining for the presence of 4-hydroxy-2-nonenal, 2,4
      dinitrophenol and 3-nitrotyrosine protein adducts and lipid accumulation in
      kidney. CA administration attenuated these pathological renal alterations.
      CONCLUSIONS: The benefits of CA in this model suggest the therapeutic use of CA
      to counter the kidney changes associated with metabolic syndrome.

PMID- 18093215
TI  - Medical compression stocking (MCS).

PMID- 18093216
TI  - Sentinel lymph node status is the most important prognostic factor for thick (>
      or = 4 mm) melanomas.
AB  - BACKGROUND: The value of the status of the sentinel lymph node (SLN) in patients
      with thick melanomas (Breslow thickness > or = 4 mm) is controversial. PATIENTS
      AND METHODS: Using Kaplan-Meier estimates and Cox regression models, we studied
      152 patients with primary melanomas > or = 4 mm thickness who underwent sentinel
      lymph node excision (SLNE) at the university hospitals of Hannover and Gottingen,
      Germany, between 1998 and 2006. RESULTS: The median tumor thickness was 5.2 (4
      18) mm; 58.5% of primary melanomas were ulcerated. Micrometastasis to a SLN was
      found in 48.7%. The patients with positive SLNs were significantly younger than
      those with negative SLN (p = 0.01). Of the complete lymph node dissections, 32%
      contained positive non-SLN. The estimated 5 year recurrence-free survival was
      42.5 +/- 5% (+/- standard error) (26.3 +/- 6.6% after positive SLNE, 58.7 +/-
      7.1% after negative SLNE). The 5 year overall survival rate was 53.2 +/- 5.4%
      (37.5 +/- 8.1% after positive SLNE, 67.6 +/- 6.7% after negative SLNE). By
      multivariate analysis, the SLN was a highly significant predictor for overall
      survival (p = 0.007, relative risk 2.3, 95%, confidence interval 1.2-4.2). The
      overall survival was significantly associated with penetration of nodal
      metastases into the SLN > 0.3 mm (p = 0.001). Other parameters such as tumor
      thickness, ulceration, age and sex were not significant. In the subgroup of
      patients with negative SLN, neither tumor thickness nor ulceration was
      significant. CONCLUSIONS: The status of the SLN represents the most important
      prognostic parameter in patients with thick melanomas, whereas other parameters
      such as tumor thickness and ulceration loose their prognostic value.

PMID- 18093217
TI  - Urticaria associated with Norovirus infection: report of two cases.
AB  - Acute and chronic urticaria may be triggered by infection. Streptococci and
      Helicobacter pylori are the most frequent acute infectious causes. We present two
      cases in which we cultured Norovirus in the stool of patients with both acute and
      chronic urticaria. Noroviruses (genus Norovirus, family Caliciviridae) are a
      group of single stranded RNA, nonenveloped viruses which cause acute
      gastroenteritis in humans. Norovirus was recently approved as the official genus
      name for the group of viruses provisionally described as Norwalk-like viruses
      (NLV). Therapy is symptomatic. Noroviruses should be regarded as possible
      infectious trigger for dermatologic diseases. In seeking a focus of viral or
      bacterial infection for skin diseases with unknown origin, stool cultures should
      be part of the routine evaluation.

PMID- 18093218
TI  - Acne inversa.
AB  - Acne inversa is a chronic inflammatory skin disease featuring cutaneous and
      subcutaneous nodular inflammation, fistula formation and discharge of foul
      smelling secretions. The disease can lead to functional impairment and
      psychological problems. There is inflammation of the terminal hair follicles in
      intertriginous regions, especially perianal, axillary and inguinal areas. Less
      often there is submammary, periumbilical, retroauricular or nuchal involvement.
      Without treatment the disease is chronic and progressive. The causes of acne
      inversa are multifactorial and pathogenesis is still not well understood. Besides
      a positive family history, obesity and cigarette smoking are trigger factors.
      Early diagnosis and therapy of acne inversa saves the patient years of suffering.
      The most effective treatment is undoubtedly the radical wide excision of the
      affected areas. Local measures such as radiotherapy, photodynamic therapy and
      cryotherapy have provided little benefit; the same is true for systemic
      antibiotic treatment or hormonal therapy with anti-androgens. TNF-alpha
      antagonists seem to have a promising influence on the disease. Further studies
      investigating the effect of these substances on acne inversa are warranted.

PMID- 18093219
TI  - Intraoperative smear cytology of meningeal melanocytoma of the posterior fossa.

PMID- 18093220
TI  - Chlamydia trachomatis detection in cervical PreservCyt specimens from an Irish
      urban female population.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of cervical
      Chlamydia trachomatis infection by polymerase chain reaction (PCR) in urban women
      undergoing routine cervical cytological screening and to investigate the
      relationship with age, cytology, smoking status and concurrent human
      papillomavirus (HPV) infection. METHODS: A total of 996 women (age range 16-69
      years) attending general practitioners for routine liquid-based cervical smear
      screening in the Dublin area were recruited in the study of prevalence of C.
      trachomatis. Informed consent was obtained and liquid-based cytology (LBC)
      specimens were sent for cytological screening. DNA was extracted from residual
      LBC and tested for C. trachomatis by PCR using the highly sensitive C.
      trachomatis plasmid (CTP) primers and for HPV infection using the MY09/11 primers
      directed to the HPV L1 gene in a multiplex format. RESULTS: The overall
      prevalence of C. trachomatis was 5.4%. Prevalence was highest in the <25 years
      age group (10%). Coinfection with HPV and C. trachomatis occurred in 1% of the
      screening population. A higher rate of smoking was observed in women positive for
      C. trachomatis, HPV infections or those with abnormal cervical cytology.
      Chlamydia trachomatis infection was not associated with abnormal cytology.
      CONCLUSIONS: Women (5.4%) presenting for routine cervical screening are infected
      with C. trachomatis. Opportunistic screening for C. trachomatis from PreservCyt
      sample taken at the time of cervical cytological screening may be a possible
      strategy to screen for C. trachomatis in the Irish female population.

PMID- 18093221
TI  - Effect of gold nanoparticle on the microscopic morphology of white blood cell.
AB  - BACKGROUND: In medicine, there is limited knowledge on the toxicity of
      nanoparticles. In medicine, there has been limited knowledge on the effect of
      nanoparticles on the white blood cell. OBJECTIVE: To evaluate the effect of gold
      nanoparticle on the microscopic morphology of white blood cell. SETTING:
      Chulalongkorn Univesity, Bangkok, Thailand. METHOD: This study was performed as
      an experimental study. Mixture of gold nanoparticle solution and blood sample was
      prepared and analysed. RESULT: This work revealed that after mixing the blood
      sample with gold nanoparticle solution, accumulation of gold nanoparticle in the
      white blood cell was observed. CONCLUSION: The effect of gold nanoparticle on the
      white blood cell can be detected and this knowledge can be used in cytotoxic drug
      treatment.

PMID- 18093222
TI  - The effect of lubricant contamination on ThinPrep (Cytyc) cervical cytology
      liquid-based preparations.
AB  - OBJECTIVES: To assess the extent of lubricant use by smear-takers and the effect
      of lubricant contamination of ThinPrep processed cervical cytology samples.
      METHODS: All primary care smear-takers were sent a questionnaire on lubricant
      type and frequency of use. Fifty cervical cytology samples were then contaminated
      with incremental amounts of K-Y jelly, 50 samples contaminated with incremental
      amounts of Aquagel and ten non-contaminated vials were processed using the
      ThinPrep T2000 processor followed by Papanicolaou staining. The morphological
      appearances of lubricant contamination were described microscopically and formal
      cell counts performed on all slides. RESULTS: Seventy of 94 (74.5%) primary care
      smear-takers indicated lubricant use of whom 9/70 (12.8%) used Aquagel and 61/70
      (87.2%) used K-Y jelly. K-Y jelly appeared as mucoid blue deposits in the slide
      background whereas Aquagel appeared as pink stringy background material. Cell
      counting showed a significant difference between Aquagel and K-Y jelly
      contaminated slides compared to the original non-contaminated preparations for
      all fields and the average fields (P < 0.001) with a significantly higher count
      for the original non-contaminated slides than the lubricant contaminated groups.
      CONCLUSION: Lubricant contamination of ThinPrep cervical cytology samples may
      result in reduced cellularity of the subsequent slide. This study provides
      evidence-based data to support British Society for Clinical Cytology
      recommendations for no lubricant use when taking cervical samples.

PMID- 18093223
TI  - Peritoneal dissemination of a malignant glioma.

PMID- 18093224
TI  - Heparin-binding epidermal growth factor-like growth factor inhibits adipocyte
      differentiation at commitment and early induction stages.
AB  - Adipocytokines, bioactive molecules secreted from adipose tissues, play important
      roles in physiology, development, and disease. Recently, heparin-binding
      epidermal growth factor-like growth factor (HB-EGF) was identified as an
      adipocytokine whose expression correlates with obesity. However, the biological
      role of fat-secreted HB-EGF is still unclear. In this study, we investigated the
      effects of HB-EGF on the adipocyte differentiation of C3H10T1/2 pluripotent
      mesenchymal cells. Upon adipogenic conversion of C3H10T1/2 cells, HB-EGF
      displayed dynamic changes in expression where an initial decrease was followed by
      increased levels of expression at later stages. HB-EGF treatment during
      adipogenic induction inhibited lipid accumulation and decreased the expression of
      adipocyte molecular markers (fatty acid-binding protein, peroxisome proliferator
      activated receptor gamma, and CAAT enhancer-binding protein alpha) and lipogenic
      genes (glucose transporter, fatty acid synthetase, and lipoprotein lipase).
      Therefore, HB-EGF has an inhibitory effect on adipocyte differentiation.
      Administration of HB-EGF at various intervals during adipocyte differentiation
      revealed that HB-EGF acts during the early stages of adipocyte differentiation,
      but not at the later stages of differentiation. Furthermore, HB-EGF was able to
      block the commitment of pluripotent mesenchymal cells to the adipocyte lineage
      triggered by bone morphogenic protein 4 treatment. These data suggest that HB-EGF
      acts as a negative regulator of adipogenesis by inhibiting the commitment and
      early differentiation of the adipose lineage. The inhibitory role of HB-EGF on
      adipocyte differentiation of pluripotent mesenchymal cells sheds light on
      potential mechanisms that control adipose tissue homeostasis.

PMID- 18093225
TI  - Interdependent fibroblast growth factor and activin A signaling promotes the
      expression of endodermal genes in differentiating mouse embryonic stem cells
      expressing Src Homology 2-domain inactive Shb.
AB  - The mechanisms controlling endodermal development during stem cell
      differentiation have been only partly elucidated, although previous studies have
      suggested the participation of fibroblast growth factor (FGF) and activin A in
      these processes. Shb is a Src homology 2 (SH2) domain-containing adapter protein
      that has been implicated in FGF receptor 1 (FGFR1) signaling. To study the
      putative crosstalk between activin A and Shb-dependent FGF signaling in the
      differentiation of endoderm from embryonic stem (ES) cells, embryoid bodies (EBs)
      derived from mouse ES cells overexpressing wild-type Shb or Shb with a mutated
      SH2 domain (R522K-Shb) were cultured in the presence of activin A. We show that
      expression of R522K-Shb results in up-regulation of FGFR1 and FGF2 in EBs.
      Addition of activin A to the cultures enhances the expression of endodermal genes
      primarily in EBs expressing mutant Shb. Inhibition of FGF signaling by the
      addition of the FGFR1 inhibitor SU5402 completely counteracts the synergistic
      effects of R522K-Shb and activin A. In conclusion, the present results suggest
      that expression of R522K-Shb enhances certain signaling pathways downstream of
      FGF and that an interplay between FGF and activin A participates in ES cell
      differentiation to endoderm.

PMID- 18093226
TI  - Chromatin in early mammalian embryos: achieving the pluripotent state.
AB  - Gametes of both sexes (sperm and oocyte) are highly specialized and
      differentiated but within a very short time period post-fertilization the
      embryonic genome, produced by the combination of the two highly specialized
      parental genomes, is completely converted into a totipotent state. As a result,
      the one-cell-stage embryo can give rise to all cell types of all three embryonic
      layers, including the gametes. Thus, it is evident that extensive and efficient
      reprogramming steps occur soon after fertilization and also probably during early
      embryogenesis to reverse completely the differentiated state of the gamete and to
      achieve toti- or later on pluripotency of embryonic cells. However, after the
      embryo reaches the blastocyst stage, the first two distinct cell lineages can be
      clearly distinguished--the trophectoderm and the inner cells mass. The de
      differentiation of gametes after fertilization, as well as the differentiation
      that is associated with the formation of blastocysts, are accompanied by changes
      in the state and properties of chromatin in individual embryonic nuclei at both
      the whole genome level as well as at the level of individual genes. In this
      contribution, we focus mainly on those events that take place soon after
      fertilization and during early embryogenesis in mammals. We will discuss the
      changes in DNA methylation and covalent histone modifications that were shown to
      be highly dynamic during this period; moreover, it has also been documented that
      abnormalities in these processes have a devastating impact on the developmental
      ability of embryos. Special attention will be paid to somatic cell nuclear
      transfer as it has been shown that the aberrant and inefficient reprogramming may
      be responsible for compromised development of cloned embryos.

PMID- 18093227
TI  - Multipotent cells from the human third molar: feasibility of cell-based therapy
      for liver disease.
AB  - Adult stem cells have been reported to exist in various tissues. The isolation of
      high-quality human stem cells that can be used for regeneration of fatal deseases
      from accessible resources is an important advance in stem cell research. In the
      present study, we identified a novel stem cell, which we named tooth germ
      progenitor cells (TGPCs), from discarded third molar, commonly called as wisdom
      teeth. We demonstrated the characterization and distinctiveness of the TGPCs, and
      found that TGPCs showed high proliferation activity and capability to
      differentiate in vitro into cells of three germ layers including osteoblasts,
      neural cells, and hepatocytes. TGPCs were examined by the transplantation into a
      carbon tetrachloride (CCl4)-treated liver injured rat to determine whether this
      novel cell source might be useful for cell-based therapy to treat liver diseases.
      The successful engraftment of the TGPCs was demonstrated by PKH26 fluorescence in
      the recipient's rat as to liver at 4 weeks after transplantation. The TGPCs
      prevented the progression of liver fibrosis in the liver of CCl4-treated rats and
      contributed to the restoration of liver function, as assessed by the measurement
      of hepatic serum markers aspartate aminotransferase and alanine aminotransferase.
      Furthermore, the liver functions, observed by the levels of serum bilirubin and
      albumin, appeared to be improved following transplantation of TGPCs. These
      findings suggest that multipotent TGPCs are one of the candidates for cell-based
      therapy to treat liver diseases and offer unprecedented opportunities for
      developing therapies in treating tissue repair and regeneration.

PMID- 18093228
TI  - Identification of genes differentially expressed by prematurely fused human
      sutures using a novel in vivo - in vitro approach.
AB  - Craniosynostosis is the premature fusion of calvarial sutures. It results from
      abnormal differentiation or proliferation of cells within the osteogenic fronts
      of growing calvarial bones. To date, research has focused on animal models and in
      vitro organ and tissue culture to determine the molecular mechanisms controlling
      calvarial suture morphogenesis. Here, we test a new, in vivo-in vitro approach
      based on the hypothesis that calvarial suture cells passaged in minimal medium
      exhibit a stable gene expression profile similar to undifferentiated osteoblastic
      cells that can provide a benchmark for comparison with in vivo expression of
      differentiated tissue. We show that tissue-specific expression is lost after the
      first passage and, using cDNA microarrays, compare expression between fused
      suture tissue from craniosynostosis patients and in vitro de-differentiated
      explant cells. A large number of differentially expressed genes were identified,
      including novel genes WIF1, LEF1, SATB2, RARRES1, DEFA1, DMP1, PTPRZ1, and PTPRC,
      as well as those commonly associated with human suture morphogenesis, e.g., FGF2,
      MSX2, and BMP2. Two differentially expressed genes, WIF1 and FGF2, were further
      examined in an in vivo-in vivo comparison between unfused and prematurely fused
      tissue. The same pattern of differential expression was observed in each case,
      further validating the ability of our in vivo-in vitro approach to identify genes
      involved in in vivo human calvarial tissue differentiation.

PMID- 18093229
TI  - Association between rural residency, group D streptococcal endocarditis and colon
      cancer?

PMID- 18093230
TI  - Assessment by electron-microscopy of recombinant Vibrio cholerae and Salmonella
      vaccine strains expressing enterotoxigenic Escherichia coli-specific surface
      antigens.
AB  - Diarrhoea caused by enterotoxigenic Escherichia coli (ETEC) requires adhesion of
      microorganisms to enterocytes. Hence, a promising approach to immunoprophylaxis
      is to elicit antibodies against colonisation factor antigens (CFAs). Genes
      encoding the most prevalent ETEC-specific surface antigens were cloned into
      Vibrio cholerae and Salmonella vaccine strains. Expression of surface antigens
      was assessed by electron-microscopy. Whereas negative staining was effective in
      revealing CFA/I and CS3, but not CS6, immunolabelling allowed identification of
      all surface antigens examined. The V. cholerae vaccine strain CVD103 did not
      express ETEC-specific colonisation factors, whereas CVD103-HgR expressed CS3
      only. However, expression of both CFA/I and CS3 was demonstrated in Salmonella
      Ty21a.

PMID- 18093231
TI  - Subtle changes in ADMA and l-arginine concentrations in normal pregnancies are
      unlikely to account for pregnancy-related increased flow-mediated dilatation.
AB  - BACKGROUND: Our objective was to investigate whether serum concentrations of
      asymmetric dimethylarginine (ADMA) or l-arginine correlate to hyperlipidemia or
      endothelial function in normal pregnancy compared with the non-pregnant subjects.
      METHODS AND RESULTS: As a part of population-based, prospective cohort
      Cardiovascular Risk in Young Finns study conducted in Finland we examined 57
      pregnant Finnish women throughout gestation and 62 control women matched for age
      and smoking. Serum glucose, triglycerides (TG), total cholesterol (TC), low
      density cholesterol (LDL-C), high-density cholesterol (HDL-C) and ADMA, symmetric
      dimethylarginine (SDMA) and l-arginine were determined concomitantly with
      endothelium-dependent brachial artery flow-mediated dilation (FMD), measured by
      ultrasound. All serum lipid concentrations were significantly higher in pregnant
      women than in non-pregnant women (P < 0.001 for each). The mean serum ADMA
      concentration in pregnant women was significantly lower compared with the non
      pregnant controls (0.513 micromol l(-1) +/- 0.0593 versus 0.577 micromol l(-1) +/
      0.0710, P < 0.001). Lowered ADMA concentrations did not correlate statistically
      to FMD in these healthy pregnant women but FMD was enhanced towards the end of
      pregnancy. CONCLUSIONS: ADMA and l-arginine concentrations fall in normal
      pregnancy despite marked hypercholesterolemia. Endothelium-dependent vasodilation
      is enhanced in normal pregnancy but is not statistically correlated to maternal
      serum ADMA or l-arginine concentrations.

PMID- 18093232
TI  - IGF-1, IGFBP-3, VEGF and MMP-9 levels and their potential relationship with renal
      functions in patients with compensatory renal growth.
AB  - BACKGROUND: Mechanisms of compensatory renal growth (CRG) still remain a mystery.
      Various growth factors, including growth hormone, insulin-like growth factor-1
      (IGF-1) have been implicated in different forms of CRG. AIMS: To investigate the
      serum levels of IGF-1, vascular endothelial growth factor (VEGF - role in
      vascular remodelling), matrix metalloproteinase-9 (MMP-9 - essential for normal
      nephrogenesis) and correlation of renal function in patients with unilateral
      nephrectomized, agenesis and hypoplasic kidney. METHODS: Thirty patients were
      included in this study. In group I, there were 10 patients with unilateral
      nephrectomy, while in group II, there were 10 patients with unilateral agenesis.
      As for group III, there were 10 patients with unilateral hypoplastic kidney. The
      serum levels of IGF-1, IGF-binding protein-3 (IGFBP-3), VEGF and MMP-9 were
      studied in all the cases. Clearance of creatinin (Ccr) and protein excretion were
      examined in the 24 h urine. CRG was determined with ultrasonography and
      scintigraphy. Twenty-six control subjects were also studied. RESULTS: The levels
      of IGF-1, IGFBP-3, VEGF and MMP-9 were significantly higher in patients than in
      the control subjects (P < 0.001). Ccr and protein excretion levels were different
      in study groups than in those of the control group (P < 0.01). There were
      positive correlations between the serum levels of IGF-1 with IGFBP-3; IGF-1 with
      MMP-9; IGFBP-3 with MMP-9 (r = 0.825, P = 0.0001; P < 0.001 r = 0.611; P < 0.001
      r = 0.585, respectively). There were negative correlations between GFR and the
      serum levels of IGF-1, IGFBP-3 and MMP-9 (P < 0.01 r = -0.708; P = 0.002 r = 
      0.803; P < 0.05 r = -0.442, respectively). Furthermore, there were positive
      correlations between proteinuria and the serum levels of IGF-1, IGFBP-3 and MMP-9
      (P = 0.039 r = 0.600; P < 0.05 r = 0.456; P < 0.05 r = 0.424). CONCLUSIONS:
      Increased IGF-1, IGFBP-3, VEGF and MMP-9 were observed in CRG in the follow-up
      period. IGF-1 and MMP-9 seemed to have increased in patients with CRG in defiance
      of the development of fibrosis. Moreover, IGF-1 and MMP-9 seem to be associated
      with reduced renal function and proteinuria.

PMID- 18093233
TI  - Are green islands red herrings? Significance of green islands in plant
      interactions with pathogens and pests.
AB  - The term green island was first used to describe an area of living, green tissue
      surrounding a site of infection by an obligately biotrophic fungal pathogen,
      differentiated from neighbouring yellowing, senescent tissue. However, it has now
      been used to describe symptoms formed in response to necrotrophic fungal
      pathogens, virus infection and infestation by certain insects. In leaves infected
      by obligate biotrophs such as rust and powdery mildew pathogens, green islands
      are areas where senescence is retarded, photosynthetic activity is maintained and
      polyamines accumulate. We propose such areas, in which both host and pathogen
      cells are alive, be termed green bionissia. By contrast, we propose that green
      areas associated with leaf damage caused by toxins produced by necrotrophic
      fungal pathogens be termed green necronissia. A range of
      biotrophic/hemibiotrophic fungi and leaf-mining insects produce cytokinins and it
      has been suggested that this cytokinin secretion may be responsible for the green
      island formation. Indeed, localised cytokinin accumulation may be a common
      mechanism responsible for green island formation in interactions of plants with
      biotrophic fungi, viruses and insects. Models have been developed to study if
      green island formation is pathogen-mediated or host-mediated. They suggest that
      green bionissia on leaves infected by biotrophic fungal pathogens represent zones
      of host tissue, altered physiologically to allow the pathogen maximum access to
      nutrients early in the interaction, thus supporting early sporulation and
      increasing pathogen fitness. They lead to the suggestion that green islands are
      'red herrings', representing no more than the consequence of the infection
      process and discrete changes in leaf senescence.

PMID- 18093234
TI  - The behaviour and ecology of the zebrafish, Danio rerio.
AB  - The zebrafish Danio rerio, is an important model organism in developmental
      genetics, neurophysiology and biomedicine, but little is known about its natural
      ecology and behaviour. It is a small, shoaling cyprinid, native to the flood
      plains of the Indian subcontinent, where it is found in shallow, slow-flowing
      waters. Zebrafish are group spawners and egg scatterers, although females are
      choosy with respect to sites for oviposition and males defend territories around
      such sites. Laboratory studies of zebrafish behaviour have encompassed shoaling,
      foraging, reproduction, sensory perception and learning. These studies are
      reviewed in relation to the suitability of the zebrafish as a model for studies
      on cognition and learning, development, behavioural and evolutionary ecology, and
      behavioural genetics.

PMID- 18093235
TI  - Heteroresistance: a concern of increasing clinical significance?
AB  - Recent studies have focused on issues related to heteroresistance, including its
      definition, methods of detection and frequency. Most such studies have reported
      data concerning infections caused by Staphylococcus aureus, but the clinical
      significance of heteroresistance is unclear. Six studies have described
      infections caused by S. aureus strains that were heteroresistant to vancomycin,
      with two suggesting an association between the emergence of heteroresistance and
      treatment failure or mortality, and four suggesting no such association. Further
      studies are required to evaluate the clinical implications of heteroresistance in
      an era in which rates of antimicrobial resistance are increasing alarmingly
      worldwide.

PMID- 18093236
TI  - Genetic diversity of carbapenem-resistant isolates of Acinetobacter baumannii in
      Europe.
AB  - In total, 96 carbapenem-resistant isolates of Acinetobacter baumannii were
      obtained from 25 hospitals in 17 European countries. Imipenem MICs ranged from <4
      to 128 mg/L on retesting by Etest, with MICs > or =16 mg/L being associated with
      the carriage of genes encoding at least one other class D carbapenemase in
      addition to the intrinsic OXA-51-like enzyme. Molecular typing results obtained
      by random amplified polymorphic DNA analysis, followed by pulsed-field gel
      electrophoresis (PFGE) of ApaI-digested chromosomal DNA, were highly congruent,
      with 17 different PFGE types being delineated at a cut-off similarity level of
      85%. With few exceptions, multiple isolates from a single hospital belonged to
      the same PFGE type. Seven sequence groups were identified among the 96 A.
      baumannii isolates, with the majority of isolates (n = 81) belonging to the
      previously defined sequence groups 1 and 2, which each included eight PFGE types.
      These two multinational lineages included the previously defined European clones
      II and I, respectively, but the problem of resistant A. baumannii in Europe
      appeared not to be confined solely to these two European clones. Rather, two
      broader lineages of carbapenem-resistant A. baumannii now seem to be spreading
      throughout Europe.

PMID- 18093237
TI  - Reducing antibiotic use in influenza: challenges and rewards.
AB  - Respiratory tract infections are a frequent cause of medical consultations.
      Although the majority of such infections are viral in aetiology, they account for
      three-quarters of all antibiotic consumption, since bacterial infections of the
      upper and lower respiratory tract, notably bronchitis, sinusitis and pneumonia,
      are the most frequent complications resulting from virus infections, especially
      influenza in adults and children. The resulting widespread use of antibiotics is
      a primary factor that drives the emergence of antibiotic resistance at both the
      local and regional levels. Recent surveys suggest that the proportion of patients
      with influenza-like illness who receive antibiotics is at least double the actual
      incidence of the infections for which the treatment is intended. Inappropriate
      prescribing needs to be tackled by encouraging more rigorous diagnosis,
      prevention and treatment of viral infections, specifically influenza. Although
      accurate diagnosis of influenza is challenging, rapid tests to identify the
      causative pathogen, e.g., RT-PCR tests for influenza viruses, are becoming more
      reliable and affordable. The use of antiviral drugs, particularly neuraminidase
      inhibitors, is a specific and effective way of preventing and treating influenza,
      and has been shown to reduce the incidence of complications and associated
      antibiotic use. In contrast to bacterial resistance to antibiotics, viral
      resistance to neuraminidase inhibitors is low, and their high specificity means
      that they cannot exert selection pressure on any other species. The widespread
      adoption of these principles may have a significant effect on antimicrobial use
      and resistance.

PMID- 18093238
TI  - Molecular diagnosis of vascular access device-associated infection in children
      being treated for cancer or leukaemia.
AB  - Blood samples were collected for quantitative 16S rDNA analysis from the vascular
      access device (VAD) of patients presenting with fever at participating centres of
      the UK Children's Cancer and Leukaemia Group. In total, 260 of 301 episodes of
      fever were evaluable and were classified as probable, possible, unlikely or
      unclassifiable VAD-associated infection. The sensitivity of the 16S rDNA assay
      declined concomitantly with delays from time of presentation to sampling. The
      sensitivity with >0.125 pg of bacterial DNA/microL of whole blood was 80% for the
      20 probable VAD-associated infections diagnosed with samples collected on the day
      of or day following presentation. The specificity rose with increasing amounts of
      bacterial DNA, from 93% with >0.125 pg, to 98% with 0.25-0.5 pg, and to 100% with
      >0.5 pg/microL blood. The positive predictive value (for probable or possible)
      was 88% (95% CI 70-98%) with 0.25 pg/microL, and 100% (95% CI 83-100%) with >0.5
      pg/microL. All 18 (6.8%) episodes with >0.5 pg of bacterial DNA/microL blood were
      associated with positive blood cultures. Identifications derived from the DNA
      sequence were consistent with the blood culture identifications for 15 of the 17
      episodes with a DNA sequence identification. The VAD was removed because of
      suspected infection in six (2.8%) of 216 episodes with <0.125 pg of bacterial
      DNA/microL, in one (5%) of 20 episodes with 0.125-0.25 pg/microL, in one (16.7%)
      of six episodes with 0.25-0.5 pg/microL, and in nine (50%) of 18 episodes with
      >0.5 pg/microL. A bacterial DNA concentration of >0.5 pg/microL in blood drawn
      through a central venous catheter at the time of fever presentation had a high
      positive predictive value for VAD-associated infection and predicted an increased
      risk of VAD removal because of suspected infection.

PMID- 18093239
TI  - Assessing the validity of a statistical distribution: some illustrative examples
      from dermatological research.
AB  - BACKGROUND: Assuming a statistical distribution is one of the key points before
      conducting a statistical analysis. Goodness-of-fit tests are used to assess the
      validity of an assumed statistical distribution. In dermatological research, the
      goodness-of-fit tests used are less powerful. AIM: We recommend the use of some
      specific goodness-of-fit tests for various distributions. A graphical technique
      called quantile-quantile plotting is introduced as an additional tool to assess
      the validity of an assumed distribution. We show why one should be careful in
      selecting a goodness-of-fit method by giving some relevant examples. METHODS:
      Goodness-of-fit tests for testing normal and non-normal distributions are
      introduced. Quantile-quantile plots were constructed, and we conducted a
      simulation study for testing normality. RESULTS: We found that the Shapiro-Wilk
      statistic is the most powerful test overall to test for normal distribution.
      Quantile-quantile plotting is a very effective graphical technique to identify a
      distribution for a dataset. CONCLUSION: The use of the Shapiro-Wilk test and
      quantile-quantile plotting is recommended for testing normality.

PMID- 18093240
TI  - Association of the interleukin-10 distal promoter (-2763A/C) polymorphism with
      late-onset psoriasis.
AB  - Polymorphisms of the IL-10 promoter have been implicated in the genetic
      susceptibility to many autoimmune diseases, including psoriasis. Four putative
      functional single-nucleotide polymorphisms (SNPs) within the interleukin-10
      promoter region (-3575T/A, -2763A/C, -1082G/A and -592C/A) were analysed in 139
      patients with chronic plaque psoriasis and in 155 unrelated healthy controls from
      Thailand. There were no significant differences in the allele frequencies of any
      of the four SNPs between patients with psoriasis and controls. However, the
      frequency of the -2763A allele was increased in patients with late-onset
      psoriasis compared with controls and patients with early-onset psoriasis
      [OR=2.94, 95% CI 1.16-7.39, corrected P value (Pc)=0.04 and OR=3.26, 95% CI 1.13
      9.51, Pc=0.048, respectively]. The AAGC (-3575/-2763/-1082/-592) haplotype
      frequency was higher in late-onset compared with early onset psoriasis (OR=4.37,
      95% CI 1.24-15.97, Pc=0.027). This study suggests that the -2763A allele and the
      extended AAGC haplotype can be used as a genetic marker for susceptibility to
      late-onset psoriasis in a Thai population.

PMID- 18093241
TI  - Efficacy of local psoralen ultraviolet A treatments in psoriasis, vitiligo and
      eczema.

PMID- 18093242
TI  - Detection of anti-BP180NC16a and anti-BP230 autoantibodies in blister fluid of
      patients with bullous pemphigoid: the first survey in Greece.
AB  - Bullous pemphigoid (BP) is an acquired bullous disease with an increasing
      prevalence among elderly people worldwide, including in Greece. Blister formation
      in most patients with BP is caused by autoantibodies against structural
      components of the basement membrane zone of the skin, predominantly BP180NC16a
      and BP230 antigens on the hemidesmosome adhesion complex. Routine diagnostic
      methods such as histological examination and direct and indirect
      immunofluorescence are combined to determine diagnosis. In this study, an ELISA
      was used to measure levels of both anti-BP180NC16A and anti-BP230 autoantibodies
      in the blister fluid of 13 patients with newly diagnosed BP, before starting
      treatment. The aim of the study was to evaluate this method as a diagnostic tool
      in BP. Our results indicate that blister-fluid examination by ELISA can be a
      useful tool to diagnose bullous pemphigoid, especially in elderly patients who
      refuse biopsy or have poor venous access.

PMID- 18093243
TI  - 'Spreading bumps' on hands of a Native American.

PMID- 18093244
TI  - Management of external ear keloids using form-pressure therapy.
AB  - Keloids are a frequent finding after physical trauma. Keloids of the pinna (helix
      and antihelix) as a complication of ear-piercing are the most difficult cases.
      Clinicians have tended to avoid the surgical approach, preferring local
      conservative treatment with corticosteroids or other treatments. We report use of
      intrakeloid resection and a form-pressure device to treat pinna keloids and avoid
      recurrence. The purpose is to maintain the form of the folds of the pinna. The
      recommendation for this therapy is to maintain the pressure at 24-30 mmHg, and
      the duration of the form-pressure therapy in our patients was about 25 weeks.

PMID- 18093245
TI  - Leukaemic dissemination of Merkel cell carcinoma in a patient with systemic lupus
      erythematosus.
AB  - We describe an unusual bone-marrow metastasis of Merkel cell carcinoma (MCC)
      arising in the right cheek of a 73-year-old woman with systemic lupus
      erythematosus (SLE) and Sjogren's syndrome, who had been treated with oral
      prednisolone and methotrexate for 10 years. Seven months after wide local
      excision followed by local irradiation, the patient presented with
      thrombocytopaenia. Her bone marrow had been completely replaced by metastatic MCC
      cells, and metastatic cytokeratin 20-positive cells were also identified in the
      peripheral blood. To our knowledge, in the English literature, only six cases
      have been described previously of MCC bone-marrow involvement. Of these six
      cases, four were immunosuppressed, similar to our case. The high incidence of MCC
      in immunosuppressed patients such as those with SLE has been discussed
      previously. We consider that immunosuppression might be associated with bone
      marrow metastasis, which is a rare form of MCC.

PMID- 18093246
TI  - The efficacy of aloe vera gel in the treatment of oral lichen planus: a
      randomized controlled trial.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease that can
      be painful especially in the atrophic and erosive forms. Several therapies have
      been tried, with varying results. There is one case report in which aloe vera
      (AV) was used successfully in the treatment of lichen planus. OBJECTIVES: To
      compare the efficacy of AV and placebo in the topical management of OLP. METHODS:
      A randomized, double-blind, placebo-controlled trial was designed. Fifty-four
      patients were randomized into two groups to receive AV gel or placebo for 8
      weeks. RESULTS: Fifty-four consecutive patients (34 women and 20 men)
      participated in the study. We found erosive and ulcerative lesions in 83% and
      17%, respectively. The most common site of OLP was the lower lip. Twenty-two of
      27 patients treated with AV (81%) had a good response after 8 weeks of treatment,
      while one of 27 placebo-treated patients (4%) had a similar response (P<0.001).
      Furthermore, two patients treated with AV (7%) had a complete clinical remission.
      Burning pain completely disappeared in nine patients treated with AV (33%) and in
      one treated with placebo (4%) (P=0.005). Symptomatology improved by at least 50%
      (good response) in 17 patients treated with AV (63%) and in two treated with
      placebo (7%) (P<0.001). No serious side-effects were found in both groups.
      CONCLUSIONS: AV gel is statistically significantly more effective than placebo in
      inducing clinical and symptomatological improvement of OLP. Therefore, AV gel can
      be considered a safe alternative treatment for patients with OLP.

PMID- 18093247
TI  - Levels of organization in biology: on the nature and nomenclature of ecology's
      fourth level.
AB  - Viewing the universe as being composed of hierarchically arranged systems is
      widely accepted as a useful model of reality. In ecology, three levels of
      organization are generally recognized: organisms, populations, and communities
      (biocoenoses). For half a century increasing numbers of ecologists have concluded
      that recognition of a fourth level would facilitate increased understanding of
      ecological phenomena. Sometimes the word "ecosystem" is used for this level, but
      this is arguably inappropriate. Since 1986, I and others have argued that the
      term "landscape" would be a suitable term for a level of organization defined as
      an ecological system containing more than one community type. However,
      "landscape" and "landscape level" continue to be used extensively by ecologists
      in the popular sense of a large expanse of space. I therefore now propose that
      the term "ecoscape" be used instead for this fourth level of organization. A
      clearly defined fourth level for ecology would focus attention on the emergent
      properties of this level, and maintain the spatial and temporal scale-free nature
      inherent in this hierarchy of organizational levels for living entities.

PMID- 18093248
TI  - Neurogenesis impairment and increased cell death reduce total neuron number in
      the hippocampal region of fetuses with Down syndrome.
AB  - We previously obtained evidence for reduced cell proliferation in the dentate
      gyrus (DG) of fetuses with Down syndrome (DS), suggesting that the hippocampal
      hypoplasia seen in adulthood may be caused by defective early neuron production.
      The goal of this study was to establish whether DS fetuses (17-21 weeks of
      gestation) exhibit reduction in total cell number in the DG, hippocampus and
      parahippocampal gyrus (PHG). Volumes of the cellular layers and cell number were
      estimated with Cavalieri's principle and the optical fractionator method,
      respectively. We found that in DS fetuses all investigated structures had a
      reduced volume and cell number. Analysis of cell phenotype showed that DS fetuses
      had a higher percentage of cells with astrocytic phenotype but a smaller
      percentage of cells with neuronal phenotype. Immunohistochemistry for Ki-67, a
      marker of cycling cells, showed that DS fetuses had less proliferating cells in
      the germinal zones of the hippocampus and PHG. We additionally found that in the
      hippocampal region of DS fetuses there was a higher incidence of apoptotic cell
      death. Results show reduced neuron number in the DS hippocampal region and
      suggest that this defect is caused by disruption of neurogenesis and apoptosis,
      two fundamental processes underlying brain building.

PMID- 18093249
TI  - Systematic assessment of BDNF and its receptor levels in human cortices affected
      by Huntington's disease.
AB  - One cardinal feature of Huntington's disease (HD) is the degeneration of striatal
      neurons, whose survival greatly depends on the binding of cortical brain-derived
      neurotrophic factor (BDNF) with high-affinity (TrkB) and low-affinity
      neurotrophin receptors [p75 pan-neurotrophin receptor (p75(NTR))]. With a few
      exceptions, results obtained in HD mouse models demonstrate a reduction in
      cortical BDNF mRNA and protein, although autopsy data from a limited number of
      human HD cortices are conflicting. These studies indicate the presence of defects
      in cortical BDNF gene transcription and transport to striatum. We provide new
      evidence indicating a significant reduction in BDNF mRNA and protein in the
      cortex of 20 HD subjects in comparison with 17 controls, which supports the
      hypothesis of impaired BDNF production in human HD cortex. Analyses of the BDNF
      isoforms show that transcription from BDNF promoter II and IV is down-regulated
      in human HD cortex from an early symptomatic stage. We also found that TrkB mRNA
      levels are reduced in caudate tissue but not in the cortex, whereas the mRNA
      levels of T-Shc (a truncated TrkB isoform) and p75(NTR) are increased in the
      caudate. This indicates that, in addition to the reduction in BDNF mRNA, there is
      also unbalanced neurotrophic receptor signaling in HD.

PMID- 18093250
TI  - An orthotopic skull base model of malignant meningioma.
AB  - Meningioma tumor growth involves the subarachnoid space that contains the
      cerebrospinal fluid. Modeling tumor growth in this microenvironment has been
      associated with widespread leptomeningeal dissemination, which is
      uncharacteristic of human meningiomas. Consequently, survival times and tumor
      properties are varied, limiting their utility in testing experimental therapies.
      We report the development and characterization of a reproducible orthotopic skull
      base meningioma model in athymic mice using the IOMM-Lee cell line. Localized
      tumor growth was obtained by using optimal cell densities and matrigel as the
      implantation medium. Survival times were within a narrow range of 17-21 days. The
      xenografts grew locally compressing surrounding brain tissue. These tumors had
      histopathologic characteristics of anaplastic meningiomas including high
      cellularity, nuclear pleomorphism, cellular pattern loss, necrosis and
      conspicuous mitosis. Similar to human meningiomas, considerable invasion of the
      dura and skull and some invasion of adjacent brain along perivascular tracts were
      observed. The pattern of hypoxia was also similar to human malignant meningiomas.
      We use bioluminescent imaging to non-invasively monitor the growth of the
      xenografts and determine the survival benefit from temozolomide treatment. Thus,
      we describe a malignant meningioma model system that will be useful for
      investigating the biology of meningiomas and for preclinical assessment of
      therapeutic agents.

PMID- 18093251
TI  - Intravascular thrombosis in central nervous system malignancies: a potential role
      in astrocytoma progression to glioblastoma.
AB  - The presence of necrosis within a diffuse glioma is a powerful predictor of poor
      prognosis, yet little is known of its origins. Intravascular thrombosis is a
      frequent finding in glioblastoma [GBM; World Health Organization (WHO) grade IV]
      specimens and could potentially be involved in astrocytoma progression to GBM or
      represent a surrogate marker of GBM histology. We investigated whether
      intravascular thrombosis was more frequent or prominent in GBM than other central
      nervous system (CNS) malignancies and considered its prognostic significance in
      anaplastic astrocytoma (AA; WHO grade III), which lacks necrosis. Histologic
      sections were examined for thrombosis, necrosis and microvascular hyperplasia
      from each of 297 CNS tumors, including 103 GBMs, 46 AAs, 20 diffuse astrocytoma
      (DAs; WHO grade II), eight anaplastic oligodendrogliomas (AOs; WHO grade III), 20
      oligodendrogliomas (ODs; WHO grade II), 49 metastatic carcinomas (METs), 31
      primary central nervous system lymphomas (PCNSLs) and 20 medulloblastomas (MBs).
      Among newly diagnosed tumors, thrombosis was present in 92% of GBM resections,
      significantly greater than other types of CNS malignancies. Of tumors with
      thrombosis, GBMs had a higher frequency of affected vessels than AAs, DAs, AOs,
      ODs and MBs, but had a frequency similar to METs and PCNSLs. The sensitivity of
      thrombosis for the diagnosis of GBM in this set of tumors was 92% and the
      specificity was 91%. Intravascular thrombosis was uncommon in AAs and was only
      noted in stereotactic biopsies. This subset of patients had shorter survivals
      than those AAs without thrombosis. Thus, intravascular thrombosis is more
      frequent in GBM than other CNS malignancies. When present in AAs, it appears to
      indicate aggressive clinical behavior.

PMID- 18093252
TI  - Formulation of long-acting nifedipine tablets influences the heart rate and
      sympathetic nervous system response in hypertensive patients.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Pharmacokinetic and pharmacodynamics
      studies are usually carried out separately with theoretical linking or
      interpretations. The pharmacokinetics of short- vs. long-acting formulations of
      nifedipine is well known, but the pharmacokinetics of different once-a-day
      formulations of nifedipine is generally not well known by the practising
      physician. WHAT THIS STUDY ADDS: This study provides practical patient-based
      information linking pharmacokinetics to pharmacodynamics in one of the target
      populations of patients, those with hypertension, who might receive the two
      different drugs. AIMS The haemodynamic responses to nifedipine vary between short
      and long-acting formulations. However, the latter have not been compared despite
      marked differences in their constitution. Our 1-month randomized, crossover study
      was designed to compare the 30-mg osmotic, constant-release nifedipine
      gastrointestinal therapeutic system (N-GITS) with an encapsulated mini-tablet
      Coracten XL. METHODS: Forty-four hypertensive patients aged 63 +/- 7 years were
      studied. The formulation was changed on day 15 and (for a single dose) day 30. At
      days 0, 14, 15, 29 and 30, patients were monitored for 6 h after dosing, during
      which blood pressure (BP), heart rate (HR) and plasma levels of norepinephrine
      (NE) and nifedipine were measured. The primary outcome was the difference in
      plasma NE between formulations at the time of peak nifedipine level. RESULTS:
      Systolic BP decreased rapidly after the first dose of Coracten, achieving nadir
      at 5 h. HR rose by 1.2 +/- 8.8 beats min(-1). After N-GITS HR fell by 2.4 +/- 7.7
      beats min(-1) (P = 0.159). Plasma NE was higher in the Coracten- (480 +/- 38.3 pg
      ml(-1)) than N-GITS-treated patients (343 +/- 75.0 pg ml(-1)) at the time of peak
      nifedipine concentrations (4 and 5 h, respectively) and their change from
      baseline was significantly (P = 0.0046) different. A similar difference between
      the drugs was seen again at days 15 and 30, at 5 h after switching formulations.
      CONCLUSIONS: This study suggests that two different formulations of once-daily
      nifedipine result in different BP and plasma NE responses, and that switching
      between formulations causes opposite effects upon the sympathetic nervous
      response to falling BP.

PMID- 18093253
TI  - Does pharmacist-led medication review help to reduce hospital admissions and
      deaths in older people? A systematic review and meta-analysis.
AB  - We set out to determine the effects of pharmacist-led medication review in older
      people by means of a systematic review and meta-analysis covering 11 electronic
      databases. Randomized controlled trials in any setting, concerning older people
      (mean age > 60 years), were considered, aimed at optimizing drug regimens and
      improving patient outcomes. Our primary outcome was emergency hospital admission
      (all cause). Secondary outcomes were mortality and numbers of drugs prescribed.
      We also recorded data on drug knowledge, adherence and adverse drug reactions. We
      retrieved 32 studies which fitted the inclusion criteria. Meta-analysis of 17
      trials revealed no significant effect on all-cause admission, relative risk (RR)
      of 0.99 [95% confidence interval (CI) 0.87, 1.14, P = 0.92], with moderate
      heterogeneity (I(2) = 49.5, P = 0.01). Meta-analysis of mortality data from 22
      trials found no significant benefit, with a RR of mortality of 0.96 (95% CI 0.82,
      1.13, P = 0.62), with no heterogeneity (I(2) = 0%). Pharmacist-led medication
      review may slightly decrease numbers of drugs prescribed (weighted mean
      difference = -0.48, 95% CI -0.89, -0.07), but significant heterogeneity was found
      (I(2) = 85.9%, P < 0.001). Results for additional outcomes could not be pooled,
      but suggested that interventions could improve knowledge and adherence.
      Pharmacist-led medication review interventions do not have any effect on reducing
      mortality or hospital admission in older people, and can not be assumed to
      provide substantial clinical benefit. Such interventions may improve drug
      knowledge and adherence, but there are insufficient data to know whether quality
      of life is improved.

PMID- 18093254
TI  - Pyrazinamide blood concentrations in children suffering from tuberculosis: a
      comparative study at two doses.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Pyrazinamide is recommended in doses
      varying from 15 to 40 mg kg(-1). The most commonly used average daily dose is 25
      mg kg(-1). Its use is associated with dose dependent hepatotoxicity. Lower doses
      are not used because of lack of pharmacokinetic data especially in children.
      There is only one detailed study of pyrazinamide in children at a dose of 35 mg
      kg(-1). WHAT THIS STUDY ADDS: This is the first study evaluating serum
      concentrations of pyrazinamide in children at a dose of 15 mg kg(-1) which is on
      the lower side of the recommended dose. The study also compared the serum
      concentrations and pharmacokinetics achieved with this dose with the widely used
      dose of 25 mg kg(-1) in children suffering from tuberculosis. The
      pharmacokinetics and pharmacodynamic indices of pyrazinamide were comparable with
      the 25 and 15 mg kg(-1) doses. AIMS: To evaluate the pharmacokinetics and
      pharmacodynamic indices of pyrazinamide at doses of 15 and 25 mg kg(-1) in
      children suffering from tuberculosis. METHODS: Twenty children with tuberculosis
      received pyrazinamide at a single dose of 25 mg kg(-1) (group I) and 15 mg kg(-1)
      (group II). Serial blood samples were collected and the drug concentrations were
      analyzed spectrophotometrically. The pharmacokinetic parameters were calculated
      and the duration of time for which pyrazinamide concentrations in serum remained
      above the pyrazinamide inhibitory concentrations of 20 microg ml(-1) and 25
      microg ml(-1) was studied. RESULTS: The mean peak serum concentration was 42.4 +/
      3.3 microg ml(-1) (95% CI +/- 6.5) and 38.6 +/- 3.9 microg ml(-1) (95% CI +/-
      7.7) in groups I and II, respectively. The elimination half-life was 9.3 +/- 1.3
      h and 10.5 +/- 2.3 h (P = 0.6) and clearance was 0.06 +/- 0.01 l h(-1) kg(-1) and
      0.04 +/- 0.01 l h(-1) kg(-1) (P = 0.08) in groups I and II, respectively.
      Pharmacokinetic parameters and PKPD indices were comparable with both the doses.
      CONCLUSIONS: The study indicates that comparable serum concentrations of
      pyrazinamide are attained with 25 mg kg(-1) and 15 mg kg(-1) doses in children.
      The elimination half-life was longer and volume of distribution greater in
      children than in the adult population.

PMID- 18093255
TI  - Inhibition of placental P-glycoprotein: impact on indinavir transfer to the
      foetus.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: We have shown previously using the
      dually perfused isolated human placenta model that the maternal to foetal
      transfer of the antiviral protease inhibitor drug indinavir is substantially
      lower than the transfer in the opposite direction. This finding is not consistent
      with passive diffusion and indicates that a carrier-mediated mechanism is
      involved in retarding the movement in the maternal to foetal direction. The
      efflux transporter P-gp located in the apical membrane domain of the placental
      trophoblast cells has been implicated as the likely cause of the differential bi
      directional transport. WHAT THIS STUDY ADDS: The present study also utilizes the
      human perfused human isolated placenta to investigate the possible inhibitory
      effects of the P-gp inhibitor PSC833 and the P-gp substrate/inhibitor ritonavir
      on the maternal to foetal transfer clearance of indinavir. The studies, which
      were conducted such that each placenta served as its own control, demonstrated a
      statistically significant increase in the maternal to foetal transfer of
      indinavir in the presence of PSC833 but not in the presence of ritonavir, a
      protease inhibitor that is often used in combination with other protease
      inhibitors in dual therapy. The lack of effect of ritonavir is most likely
      related to the relatively low inhibitory activity at the clinically relevant
      concentration used in this study. AIMS: To investigate the effect of P-gp
      inhibition on the maternal to foetal transfer of indinavir. METHODS: Term human
      placentae (n = 12) were from non-HIV infected women. Maternal to foetal transfer
      of indinavir was examined in the absence and presence of P-gp inhibitors PSC833
      (n = 7) or ritonavir (n = 5), in the perfused human placenta. Antipyrine and
      [(3)H]-vinblastine were included as markers of passive diffusion and P-gp
      transport, respectively. These markers and indinavir were added to maternal
      perfusate at 0 min; PSC833 or ritonavir was added at 25 min. Steady-state
      maternal to foetal transfer clearance was calculated during control and inhibitor
      phases. Indinavir and vinblastine clearances were normalized to antipyrine
      clearance (clearance index). RESULTS: Indinavir clearance index increased between
      the control (0.25 +/- 0.03) and PSC833 phases (0.37 +/- 0.14) (95% CI of the
      difference -0.23, -0.002). Vinblastine clearance index increased from (0.25 +/-
      0.08) to (0.34 +/- 0.06) in the control and PSC833 phases, respectively (95% CI
      of difference -0.14, -0.05). Indinavir clearance index was unchanged between
      control (0.34 +/- 0.14) and ritonavir phases (0.39 +/- 0.13) (95% CI of the
      difference -0.19, 0.08). Vinblastine clearance index increased from (0.24 +/-
      0.12) to (0.32 +/- 0.12) in the control and ritonavir phases, respectively (95%
      CI of the difference -0.15, -0.009). CONCLUSIONS: Maternal to foetal transfer
      clearance of indinavir and vinblastine increased following P-gp inhibition. The
      potential role for co-administration of P-gp inhibitors with PIs to reduce
      perinatal HIV transmission warrants further investigation.

PMID- 18093256
TI  - Similarity of biotechnology-derived medicinal products: specific problems and new
      regulatory framework.

PMID- 18093257
TI  - Transfer of isoniazid from circulation to breast milk in lactating women on
      chronic therapy for tuberculosis.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Isoniazid is the most widely used first
      line antituberculosis drug. It is considered safe during lactation, but limited
      data are available on the transfer of isoniazid from circulation to milk in
      lactating women, which can provide an assessment of extent of exposure to the
      nursling. WHAT THIS STUDY ADDS: The study documents the transfer pattern and milk
      to plasma (M : P) ratio of isoniazid at a steady state. Peak plasma and milk
      concentrations of isoniazid were reached within 1 h and the projected exposure of
      the drug to the infant is much lower than the prophylactic dose, supporting its
      safety during breast feeding. AIM: To determine milk to plasma (M : P) ratios and
      infant dose (absolute and relative) for isoniazid in lactating women on
      antituberculosis therapy. METHODS: Concentrations of isoniazid in plasma and milk
      were measured in exclusively breast feeding women taking 300 mg day(-1) as
      treatment for tuberculosis. RESULTS: Peak plasma and milk concentrations of
      isoniazid were observed at 1 h. A mean M : P(AUC) value of 0.89 (95% CI 0.7, 1.1)
      was calculated for isoniazid from seven women over 24 h. The mean absolute infant
      dose was estimated to be 89.9 mug kg day(-1) (95% CI 65.6, 114) and the relative
      infant dose was 1.2% of the weight adjusted maternal dose. CONCLUSIONS: The mean
      relative dose of isoniazid (1.2%) transmitted to the infant via breast milk is
      below the 10% notional level of concern. These data suggest that isoniazid
      therapy is safe during breastfeeding.

PMID- 18093258
TI  - Determinants of chronic benzodiazepine use in the elderly: a longitudinal study.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * The risk of adverse events due to
      chronic benzodiazepine use is high in the elderly. * Cross-sectional studies have
      shown that increasing age, female gender and poor physical and mental health are
      associated with benzodiazepine use. * When users were re-examined some years
      later, chronic somatic disease, pain and stress seemed to contribute to the
      continuation of benzodiazepine use. WHAT THIS STUDY ADDS: * This is the first
      longitudinal study that analyzed the determinants of new-onset chronic
      benzodiazepine use in community-dwelling elderly. * Symptoms of depression,
      hypertension, pain related joint complaints and the perception of poor physical
      health predicted new-onset chronic use. Living alone was found to decrease the
      risk of chronic use. AIMS: The risk of adverse events due to chronic
      benzodiazepine use is high in the elderly. Clinicians need to be able to identify
      those persons who are at risk of chronic benzodiazepine use, but little is known
      about the determinants. This study determined social and health related factors
      that predict new-onset chronic benzodiazepine use in community-dwelling elderly.
      METHODS: This study was embedded in an ongoing cohort study among 5364 persons
      aged >or=57 years. Drug-dispensing medication records were available for the
      period between 1991 and 2003. We defined chronic benzodiazepine use as use during
      at least 180 days in a period of 365 consecutive days. The association of various
      social, psychiatric and somatic variables with new-onset chronic benzodiazepine
      use was studied with a Cox proportional hazards analysis. RESULTS: Symptoms of
      depression, hypertension, pain related joint complaints and the perception of
      poor physical health predicted new-onset chronic use. In the subsample of
      participants who had filled at least one prescription in the follow-up period, of
      these variables only pain related joint complaints increased the risk of new
      onset chronic use. Living alone protected against chronic benzodiazepine use.
      CONCLUSIONS: The elderly with poor mental and physical health are at an increased
      risk of chronic benzodiazepine use. Living alone was found to decrease the risk
      of chronic use, which suggests that social factors may determine drug usage
      patterns. Very few characteristics predicted chronic benzodiazepine use once
      patients had received their first prescription. For clinicians, identification of
      patients at high risk is therefore not straightforward.

PMID- 18093259
TI  - Dry-eye syndrome after allogeneic stem-cell transplantation in children.
AB  - PURPOSE: To report the prevalence of dry-eye syndrome (DES) in children and young
      adults treated with allogeneic stem-cell transplantation (SCT) during childhood;
      to relate DES to conditioning regimes, including total body irradiation (TBI) and
      chemotherapy, and to immunosuppressive drugs and graft-versus-host disease
      (GVHD). METHODS: This cross-sectional study included 60 children/young adults
      transplanted because of leukaemia, various haematological disorders and inborn
      errors of metabolism between 1986 and 2004, with a follow-up time of 7.0 years
      (median, range 2-18). Clinical assessments, performed at a median age of 15.6
      years (range 5.5-23.5), included an inquiry form on dry-eye symptoms, corneal
      status including fluorescein staining, 'break-up time' (BUT) and Schirmer test.
      RESULTS: A total of 37 of 60 patients had DES defined as presence of corneal
      epithelial lesions with a pathological BUT and/or Schirmer test. Twenty-nine had
      had staining <1-10% of the corneal surface while eight patients had staining > or
      =10-25% of the corneal surface. All 37 patients with objective signs of DES,
      graded and not graded, had significant associations to subjective symptoms of dry
      eyes including dry eyes, red eyes, ocular irritation, secretion and sensitivity
      to light. Frequent occasions (above median; n = 7) of high cyclosporine A trough
      levels above 250 ng/ml were associated significantly with DES (P = 0.002).
      However, there was no association between DES and conditioning with single-dose
      (s-TBI) or fractionated TBI (f-TBI), busulfan or other chemotherapy. There were
      no associations between prolonged corticosteroid treatment or chronic GVHD and
      DES in the present study. DES was more common in patients with malignant diseases
      (P = 0.02). Malignant disease increased the risk of DES in girls but not in boys.
      Increased age at SCT increased the risk for DES in boys but not in girls (P =
      0.02). Although severe keratitis occurred in three patients, nobody suffered
      corneal perforation. CONCLUSION: DES with epithelial punctata keratopathy was
      common in children/young adults treated with SCT and more common if the patients
      were exposed to repeated high trough levels of cyclosporine A; however, DES was
      not associated with irradiation, corticosteroids or GVHD in the present study.
      Patients with objective DES also had subjective symptoms of dry eyes, which
      facilitate diagnosis. Girls with malignant diseases and boys who underwent SCT at
      later ages seem to demand higher attention and more frequent check-ups regarding
      DES. Patients with diagnosed severe DES needed frequent and continuous
      ophthalmological care to maintain treatment motivation.

PMID- 18093261
TI  - Pascal, ICare and Goldmann applanation tonometry--a comparative study.
AB  - PURPOSE: To compare intraocular pressure (IOP) measurements by Pascal, ICare and
      Goldmann applanation tonometry (GAT), to evaluate the effects of central corneal
      thickness (CCT) and curvature on IOP measurement and to estimate the intra
      observer variability. METHODS: A prospective, single-centre study of 150 eyes
      with a wide range of pressures. Six masked IOP measurements/method; corneal
      thickness and curvature were studied for each eye. GAT was the reference.
      RESULTS: IOPPascal and IOPICare correlated with IOPGAT (r = 0.91, 0.89). Mean
      ICare measurement exceeded GAT by 2 mmHg. Pascal measured higher than GAT at low
      IOPs and lower at high IOPs. For every 10 mmHg increase in IOP above 31 mmHg,
      Pascal measured 2 mmHg lower than GAT and vice versa. CCT was correlated
      significantly with IOPGAT (r = 0.23) and IOPICare (r = 0.43) but not with
      IOPPascal (P = 0.12). CCT was correlated with age. In a subgroup (>50 years),
      ICare and the difference between IOPGAT and IOPPascal were affected significantly
      by the CCT, whereas IOPGAT and IOPPascal were not. Corneal curvature was
      correlated significantly with IOPGAT (r = -0.27) and IOPPascal (r = -0.26) but
      not with IOPICare (P = 0.60). Intra-observer variability within each set of six
      measurements was approximately 2 mmHg, irrespective of method. CONCLUSION: This
      study showed a reasonable overall correlation and concordance between the IOP
      obtained with the three instruments. None of the methods were completely
      independent of the biomechanical properties of the cornea. ICare showed a
      significant dependency upon CCT, whereas GAT and Pascal showed a significant
      dependency on corneal curvature. All methods showed intra-observer variability,
      which leaves room for further improvement of methods.

PMID- 18093260
TI  - The Pyhajarvi Cataract Study. I. Study design, baseline characteristics and the
      demand for cataract surgery.
AB  - PURPOSE: The Pyhajarvi Cataract Study aims to study demand for cataract surgery
      in the population of a rural town in Finland. METHODS: A random, population-based
      sample of 881 persons aged > or = 60 years were interviewed by telephone to
      obtain a Visual Function-14 (VF-14) score. A total of 294 persons were invited
      for an ophthalmic examination based on three categories of VF-14 score. Of these,
      230 (78%) responded, 10 of whom were excluded as a result of prior bilateral
      surgery. The New Zealand Priority Criteria (NZPC) and the 15-Dimension Quality of
      Life (15-D) instruments were administered. In addition, another group of 96
      patients waiting for cataract surgery were examined and scored using the VF-14,
      NZPC and 15-D instruments. A modified Lens Opacities Classification System (LOCS)
      III classification was used for grading the cataract. RESULTS: Only one (0.5%) of
      the 220 examined subjects was referred for cataract surgery. Many patients with
      relatively good visual acuity (VA), including six people with a 100-point VF-14
      score suggesting no visual symptoms, were waiting for surgery. Demographic
      factors were not associated with access to cataract surgery. The patients
      examined from the waiting list for cataract surgery had more cataractous changes
      in the lens(es), poorer VA, were older, and scored higher on the NZPC instrument
      than the population sample examined. CONCLUSIONS: Practically no hidden demand
      for cataract surgery was found in the study population as defined by the national
      criteria for cataract surgery in Finland. This reflects the fact that the current
      Finnish health care system appears to recognize and treat cataract patients very
      well, even in rural areas. Although VA tests may not be sufficient for evaluating
      need for cataract surgery, the role of questionnaires is not clear either.

PMID- 18093262
TI  - Multiple retinal haemorrhages in diabetic retinopathy after adjunctive
      intravitreal bevacizumab (Avastin) with pars plana vitrectomy.

PMID- 18093263
TI  - Usefulness of inflammatory and haemostatic markers to predict short-term risk for
      death in middle-aged ischaemic stroke patients.
AB  - OBJECTIVES: There is increasing evidence that inflammation and hypercoagulability
      play an important role in the pathophysiology of acute ischaemic stroke. We
      examined the in-hospital prognostic value on mortality of C-reactive protein
      (CRP), tumour necrosis factor-alpha (TNF-alpha), fibrinogen and D-dimer in middle
      aged ischaemic stroke patients. MATERIALS AND METHODS: We recruited 231
      consecutive patients <66 years with acute ischaemic stroke. CRP, TNF-alpha,
      fibrinogen and D-dimer levels were determined within 12 h from admission.
      RESULTS: Fifteen (6.5%) patients died during hospitalization. CRP, fibrinogen and
      D-dimer levels were significantly higher in patients who died compared with those
      who survived but only CRP and fibrinogen were independently associated with
      death, after adjusting for various confounding factors. For 1 mg/l increase in
      CRP there was a 20% higher risk of dying while for 10 mg/dl increase in
      fibrinogen the additive risk was 18%. CRP levels >18 mg/l and fibrinogen levels
      >490 mg/dl were the optimal points that discriminated those who died from the
      rest. CONCLUSIONS: CRP and fibrinogen levels can predict independently the risk
      of early death in middle-aged ischaemic stroke patients emphasizing the role of
      inflammation and coagulation in the evolution of ischaemic stroke.

PMID- 18093264
TI  - Qualification of biomarkers for drug development in organ transplantation.
AB  - The drug development process is dependent upon having established end points for
      measuring drug efficacy and adverse effects. New drug development in organ
      transplantation suffers from having end points which are either outdated or which
      do not serve the purpose of addressing the current critical drug therapy
      problems. Numerous biomarkers have been examined in organ transplantation, but
      almost all would be classified as exploratory for drug development purposes. Some
      of the possible pathways out of this dilemma include investigator- or consortium
      initiated research that would qualify the biomarkers as either probable or known
      valid biomarkers, help in identification of new end points in transplantation and
      their associated biomarkers, co-development of a new biomarker and drug for
      transplantation and the use of new clinical trial design methods which facilitate
      enriched or stratified transplant patient populations. With new biomarkers and
      new study design methodologies for drug development, improvement in the drug
      development process for transplantation is a real possibility that the transplant
      clinical and research community can help to bring about.

PMID- 18093265
TI  - The role of angiogenic and wound repair factors during CMV-accelerated transplant
      vascular sclerosis in rat cardiac transplants.
AB  - Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a
      consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be
      localized to TVS lesions, the low number of infected cells suggests a global
      effect on target tissues. We used microarray analysis followed by real-time
      polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac
      transplant model to determine whether CMV activates host WR and AG factors.
      Dysregulated cellular genes in allografts from RCMV-infected recipients were
      compared to those from uninfected recipients and native hearts. We demonstrated
      that RCMV upregulates the genes involved in WR and AG, which was highest during
      the critical time of TVS acceleration (21-28 days). Using a standard in vitro AG
      assay, virus and serum-free supernatants collected at 48 h postinfection
      significantly induced endothelial cell (EC) migration, branching and tubule
      formation compared to supernatants from mock-infected cells. Supernatants from
      ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating
      that virus replication is required. Upregulation of WR and AG genes occurs during
      the critical period of CMV-accelerated TVS. Targeting these genes may prevent
      this process and improve allograft survival.

PMID- 18093266
TI  - HIV-infected liver and kidney transplant recipients: 1- and 3-year outcomes.
AB  - Improvements in human immunodeficiency virus (HIV)-associated mortality make it
      difficult to deny transplantation based upon futility. Outcomes in the current
      management era are unknown. This is a prospective series of liver or kidney
      transplant recipients with stable HIV disease. Eleven liver and 18 kidney
      transplant recipients were followed for a median of 3.4 years (IQR [interquartile
      range] 2.9-4.9). One- and 3-year liver recipients' survival was 91% and 64%,
      respectively; kidney recipients' survival was 94%. One- and 3-year liver graft
      survival was 82% and 64%, respectively; kidney graft survival was 83%. Kidney
      patient and graft survival were similar to the general transplant population,
      while liver survival was similar to the older population, based on 1999-2004
      transplants in the national database. CD4+ T-cell counts and HIV RNA levels were
      stable; and there were two opportunistic infections (OI). The 1- and 3-year
      cumulative incidence (95% confidence intervals [CI]) of rejection episodes for
      kidney recipients was 52% (28-75%) and 70% (48-92%), respectively. Two-thirds of
      hepatitis C virus (HCV)-infected patients, but no patient with hepatitis B virus
      (HBV) infection, recurred. Good transplant and HIV-related outcomes among kidney
      transplant recipients, and reasonable outcomes among liver recipients suggest
      that transplantation is an option for selected HIV-infected patients cared for at
      centers with adequate expertise.

PMID- 18093267
TI  - Intramuscular autotransplantation of pancreatic islets in a 7-year-old child: a 2
      year follow-up.
AB  - A 7-year-old girl with severe hereditary pancreatitis underwent total
      pancreatectomy. A total of 160,000 islet equivalents (6400 islet/kg) were
      transplanted to the brachioradialis muscle of the right forearm. Her plasma C
      peptide level was undetectable after pancreatectomy but increased to 1.37 ng/mL
      after 17 days; at this time point, her insulin requirement was 0.75 units of
      insulin/kg/day. At 5- and 27-months, her hemoglobin A1c (HbA1c) and insulin
      requirements were 4.5 and 5.3% and 0.3 and 0.18 units/kg/day, respectively. Basal
      and stimulated C-peptide levels were 0.67 +/- 0.07 and 3.36 +/- 1.37 ng/mL,
      respectively. Stimulated insulin levels were 30% higher in the islet-bearing arm
      compared to the contralateral arm after glucagon stimulation. After surgery and
      islet transplantation, the quality of life improved dramatically and she gained 8
      kg of weight. In summary, a normal HbA1c, a low insulin requirement and the
      absence of recurrent hypoglycemia and the gradient of insulin between the arms
      indicate that the intramuscularly transplanted islets contribute to a long-term
      clinically significant metabolic control.

PMID- 18093268
TI  - Sticky platelet syndrome: a manageable risk factor for posttransplant
      thromboembolic events.

PMID- 18093269
TI  - Alemtuzumab (Campath-1H) in kidney transplantation.
AB  - Kidney transplantation has become the treatment of choice for both the quality of
      life and survival in patients with end-stage renal disease (ESRD). However, the
      immunosuppressive regimen which allows optimal kidney transplant outcome remains
      elusive. One of the more promising induction agents, Alemtuzumab, was introduced
      to kidney transplantation by Calne in the late 1990s with low dose cyclosporine A
      monotherapy, with the hope of establishing 'prope' or near tolerance. Subsequent
      pilot studies with Alemtuzumab alone or monotherapy (DSG, Rapa) demonstrated high
      rates of acute rejection (AR) along with occasional humoral components that lead
      to abandoning the concept of Alemtuzumab as a 'magic bullet' to achieve
      tolerance, prope or otherwise. A number of programs (including our own) has since
      modified maintenance immunosuppression using low dose tacrolimus, and shown
      acceptable rates of AR, with relatively low incidence of viral infection and
      lymphoproliferative disorders along with cost benefit. However, there are only
      three prospective, randomized studies which are small with one year or less
      follow-up, and most published series utilize historical control groups with
      relatively short follow-up. As extrapolation from short-term data is far from
      secure, long-term, prospective, randomized studies with Alemtuzumab will be
      necessary to determine the optimal immunosuppressive regimen.

PMID- 18093270
TI  - Kidney paired donation with compatible pairs.

PMID- 18093271
TI  - Update on immunizations in solid organ transplant recipients: what clinicians
      need to know.
AB  - Vaccine-preventable diseases remain a major source of morbidity and mortality in
      transplant recipients. Since the publication of the American Society of
      Transplantation's guidelines for vaccination of solid organ transplant recipients
      in 2004 (1), several new vaccines have been licensed. Transplant clinicians have
      been inundated by questions from patients and colleagues regarding the utility
      and safety of these vaccines in transplant candidates and recipients. In
      addition, new data has appeared regarding utility of some established vaccines,
      lack of rejection after vaccination and newer adjuvant strategies. Literature
      published between 2004 and 2007 was reviewed in a Medline search. Guidelines from
      the Centers for Disease Control and Prevention's Advisory Committee on
      Immunization Practices are reviewed and summarized, with particular attention to
      vaccines for human papillomavirus, varicella and varicella-zoster, tetanus
      reduced diphtheria-acellular pertussis (Tdap) and hepatitis B, as well as
      conjugated meningococcal and conjugated pneumococcal vaccines. Although
      randomized controlled trials in transplant recipients have not been performed for
      most new licensed vaccines, preliminary recommendations can be formulated based
      on current data and guidelines. Further studies will be important to determine
      the indications and optimal timing of newer immunizations and immunization
      strategies.

PMID- 18093272
TI  - Hashimoto's encephalopathy after intensive lymphocyte depletion with rabbit anti
      thymocyte globulin in a renal transplant patient.
AB  - There has been no reported case of Hashimoto's encephalopathy (HE) ('steroid
      responsive encephalopathy associated with autoimmune thyroiditis', 'SREAT'), in
      the renal transplant recipient population. We describe the case of a 55-year-old
      female with Type-1 diabetes who presented 2 years posttransplantation in a
      comatose state that had developed over the preceding 24 h. The patient had
      received a short, intensive course of rATG induction at the time of
      transplantation and early steroid withdrawal. After 6 months she had been
      withdrawn from calcineurin inhibitors and was maintained on mycophenolate mofetil
      and sirolimus. Systematic workup determined the cause of her coma to be HE. High
      dose steroid therapy resulted in complete resolution of the patient's symptoms.
      The literature regarding the diagnosis, course and treatment of HE is reviewed
      and the possibility that increased use of steroid-free immunosuppression and
      intensive lymphocyte depletion regimens may increase the prevalence of de novo
      autoimmune disease is discussed.

PMID- 18093273
TI  - The utility of 1- and 3-month protocol biopsies on renal allograft function: a
      randomized controlled study.
AB  - Identification of pathological events in the renal allograft using protocol
      biopsies at predetermined time intervals may yield useful information and improve
      outcomes. We examined the influence of decisions taken on the basis of 1- and 3
      month protocol biopsies findings on 1-year renal allograft function in a
      prospective randomized study. Out of 102 living-donor allograft recipients, 52
      were randomized to undergo protocol biopsies and 50 controls had only indicated
      biopsies. All acute rejection (AR) episodes (clinical and subclinical) were
      treated. Calcineurin inhibitor (CNI) dose adjustments were made on clinical
      judgment. Baseline recipient and donor characteristics, immunosuppressive drug
      usage, HLA matches and 2-h cyclosporine levels were similar in both groups. At 1
      and 3 months, protocol biopsies revealed borderline (BL) changes in 11.5% and 14%
      patients, AR in 17.3% and 12% and chronic allograft nephropathy (CAN) in 3.8% and
      10%. The incidence of clinically evident AR episodes was similar in the two
      groups, but biopsy group had lower serum creatinine at 6 months (p = 0.0003) and
      1 year (p < 0.0001). The renal functions were similar in those with normal
      histology and BL changes. Protocol biopsies are helpful in detecting subclinical
      histological changes in the graft and improving short-term renal allograft
      function.

PMID- 18093274
TI  - Heme oxygenase-1 genotype of the donor is associated with graft survival after
      liver transplantation.
AB  - Heme oxygenase-1 (HO-1) has been suggested as a cytoprotective gene during liver
      transplantation. Inducibility of HO-1 is modulated by a (GT)(n) polymorphism and
      a single nucleotide polymorphism (SNP) A(-413)T in the promoter. Both a short
      (GT)(n) allele and the A-allele have been associated with increased HO-1 promoter
      activity. In 308 liver transplantations, we assessed donor HO-1 genotype and
      correlated this with outcome variables. For (GT)(n) genotype, livers were divided
      into two classes: short alleles (<25 repeats; class S) and long alleles (> or =25
      repeats; class L). In a subset, hepatic messenger ribonucleic acid (mRNA)
      expression was correlated with genotypes. Graft survival at 1 year was
      significantly better for A-allele genotype compared to TT-genotype (84% vs. 63%,
      p = 0.004). Graft loss due to primary dysfunction (PDF) occurred more frequently
      in TT-genotype compared to A-receivers (p = 0.03). Recipients of a liver with TT
      genotype had significantly higher serum transaminases after transplantation and
      hepatic HO-1 mRNA levels were significantly lower compared to the A-allele livers
      (p = 0.03). No differences were found for any outcome variable between class S
      and LL-variant of the (GT)(n) polymorphism. Haplotype analysis confirmed
      dominance of the A(-413)T SNP over the (GT)(n) polymorphism. In conclusion, HO-1
      genotype is associated with outcome after liver transplantation. These findings
      suggest that HO-1 mediates graft survival after liver transplantation.

PMID- 18093275
TI  - Waiting before birth: outcomes after fetal listing for heart transplantation.
AB  - Following fetal diagnosis of a profound heart defect, transplantation (HTx) is an
      alternative to pregnancy termination or neonatal surgical palliation.
      Retrospective review of the cardiac and transplant databases of fetal listings
      for HTx between 1990 and July 2006 was undertaken to describe outcomes after
      listing. We identified 26 fetal listings (of 269 total listings). Diagnoses
      included congenital heart disease (n = 24) and cardiomyopathy (n = 2). Seven
      patients were delisted after birth: in five cases parents opted for surgical
      palliation, two clinically improved. One patient died wait-listed (stillborn).
      Time wait-listed as a fetus ranged from 1-41 days (median 19 days). Eighteen
      patients underwent HTx (median weight 2.8 kg, range 2.1-10.9 kg); median days
      wait-listed after birth was 22 (4 h-123 days). Two fetuses were surgically
      delivered at 36 weeks gestation when a donor organ became available; 11 were
      transplanted as neonates (<30 days). The median age at HTx was 1 month (4 h-2.6
      months). Fetal listing for HTx increases the potential window of opportunity for
      a donor organ to become available; patients had low wait-list mortality and a
      fair intermediate-term outcome. Well-defined criteria for eligibility for fetal
      listing and priority allocation to infants over fetuses seem rational approaches
      for centers that offer fetal listing.

PMID- 18093276
TI  - Ascites in hepatitis C liver transplant recipients frequently occurs in the
      absence of advanced fibrosis.
AB  - Ascites after liver transplantation is uncommon (3-7%) but causes morbidity and
      mortality. Although hepatitis C (HCV), pretransplant ascites, encephalopathy and
      cold ischemia time have been identified as predictors, neither posttransplant
      renal function nor the severity of recurrent HCV (inflammatory grade; fibrosis
      stage) has been systematically assessed. Among 173 HCV transplants (1 January
      1998 to 31 December 2002), 18 patients (10%) developed posttransplant ascites.
      Cox proportional hazards models identified recipient female gender (hazard ratio
      [HR]= 12.18; p = 0.0001), cold ischemia time (HR = 1.17 per incremental hour; p =
      0.021) and posttransplant creatinine (Cr) (HR = 1.56 per incremental 1.0 mg/dL; p
      = 0.0052) as independent predictors. Ludwig-Batts inflammation grade (HR = 1.32;
      p = 0.36) and fibrosis stage (HR = 1.63; p = 0.12) were not significant
      predictors. The 18 recipients had 19 ascites episodes; 12/19 had fibrosis stage
      0, 1 or 2 (10/12 with stage 0 or 1). All 12 lacked diagnostic parenchymal or
      vascular histopathology. Renal function at ascites diagnosis were similar for
      transplants with fibrosis stage 0, 1 or 2 versus 3 or 4 (1.8 +/- 1.6 vs. 1.6 +/-
      0.6 mg/dL; Cr clearance 39.6 +/- 15.6 vs. 39.3 +/- 13.4 mL/min/1.73 m(2)). In
      conclusion, recipient female gender, cold ischemia time and poor posttransplant
      renal function were independent predictors of ascites after HCV liver
      transplantation. Two thirds of ascites episodes, however, occurred without
      significant fibrosis or histopathology.

PMID- 18093277
TI  - Does the permanent portacaval shunt for a small-for-size graft in a living donor
      liver transplantation do more harm than good?
AB  - In order to obviate a small-for-size graft syndrome (SFSGS), a portacaval (PC)
      shunt had been considered in a case of adult-to-adult living donor liver
      transplantation (AA-LDLT). In a recent AA-LDLT case, we adopted the PC shunt to
      resolve SFSGS; however, graft atrophy was observed in the late period of LDLT,
      thereby resulting in liver dysfunction. Due to the surgical closure of the PC
      shunt at 11 months post-LDLT, the graft regenerated gradually and resulted in the
      recovery of the liver function. This experience indicates that the portacaval
      shunt would overcome SFSGS in the early period of LDLT, while it would cause the
      graft atrophy and the graft dysfunction in the late period of LDLT.

PMID- 18093278
TI  - Immunodominance hierarchies and gender bias in direct T(CD8)-cell alloreactivity.
AB  - Allogeneic solid organ transplantation often occurs across multiple donor
      recipient HLA mismatches with consequent risk of allograft rejection. However,
      there is growing evidence that not all HLA mismatches are equivalent in their
      stimulation of allogeneic T cells making it important to determine which of these
      might be more significant as predictors of allograft rejection. To this end, we
      used defined antigen-presenting cell (APC) transfectants expressing single MHC-I
      allotypes as target cells that could discriminate the relative contribution of
      individual mismatched MHC-I allotypes to direct T-cell alloreactivity. We
      demonstrate remarkably reproducible patterns of immunodominance in reactivity
      across mismatched MHC-I allotypes. These patterns are HLA context-dependent,
      partly reflecting alloantigenic competition in responder cell responses. In
      strong alloresponses, we also observed an increased percentage of alloreactive
      T(CD8) cells in female responders, regardless of the stimulator gender,
      highlighting HLA-independent factors in the potency of the alloresponse. This
      approach provides a potential measure of specific alloreactive T cells that could
      be used in clinical practice for selection of donors, assessment of
      posttransplant outcomes, modulation of immunosuppression and detection of
      rejection episodes.

PMID- 18093279
TI  - HLA class II-like antiidiotypic antibodies from highly sensitized patients
      inhibit T-cell alloresponses.
AB  - The purpose of this study is to identify factors in the sera of highly sensitized
      (HS) patients (pts) that inhibit T-cell alloresponses. An in vitro assay was used
      to measure HLA class I and class II-like antiidiotypic antibodies (anti-ids). The
      stimulation index (SI) was used to measure PBL and T-cell responses to
      alloantigens. All HS sera (32 pts) and the IgG fraction inhibited PBL and CD4(+)
      T-cell responses to alloantigens. The SI with HS IgG was 7.9 +/- 1.7 as compared
      to 31.5 +/- 5.9 with normal IgG (p = 0.0003). In a subset of pts who were
      transiently sensitized, the SI was 6.6 +/- 1.0 with a high panel reactive
      antibody (PRA), but when their PRA was zero, the SI was 17.8 +/- 1.3 (p =
      0.0000001). Anti-ids were found in 100% of 17 pts with a high PRA. The T-cell
      inhibitory factors reduced CD4(+) T-cell responses of HS pts to alloantigens in
      the presence of autologous anti-ids, were MHC restricted and were inactivated by
      in vitro generated antibodies to HLA class II-like anti-ids. The HLA class II
      like anti-id IgG molecules bind to the TCR of CD4(+) T cells and may impair their
      ability to help in the downregulating antibody response to anti-ids.

PMID- 18093280
TI  - Role of minor histocompatibility antigens in renal transplantation.
AB  - In hematopoietic stem cell transplantation (HSCT), disparities between recipients
      and donors for minor histocompatibility antigens (mHags) have been shown to be
      related to graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL)
      effects. We investigated the effect of mHag mismatches on kidney allograft
      survival. Out of 33 785 kidney transplants on which DNA and clinical data were
      available to the Collaborative Transplant Study (CTS), 702 recipient/donor pairs
      could be identified as HLA-A, -B and -DRB1 matched first transplants of Caucasian
      origin. These pairs were typed for genetic polymorphisms of the mHags HA-1, HA-2,
      HA-3, HA-8, HB-1, ACC-1 and UGT2B17. Because mHags are presented in an HLA
      restricted manner, only HLA-A*02 positive pairs were included in the analysis of
      HA-1, HA-2 and HA-8. Similarly, only HLA-A*01, HLA-B*44 and HLA-A*24 positive
      pairs were considered for the evaluation of HA-3, HB-1 and ACC-1, respectively,
      whereas UGT2B17 compatible transplants were assessed in HLA-A*29 and HLA-B*44
      positive pairs. None of the mHag disparities showed a statistically significant
      effect on death-censored 5-year graft survival. This report represents the first
      large-scale study on the relevance of mHags in kidney transplantation.

PMID- 18093281
TI  - Association of polymorphic sites in the OCA2 gene with eye colour using the tree
      scanning method.
AB  - A number of genes are considered to affect normal variation in human
      pigmentation. Recent studies have indicated that OCA2 is the crucial gene
      involved in the high variation of iris colour present among populations of
      European descent. In this study, eleven polymorphisms of the OCA2 gene were
      examined in search of their association with different pigment traits. The
      evolutionary tree scanning method indicated that the strongest phenotypic eye
      colour variation is associated with the branch defined by nonsynonymous change
      rs1800407, which refers to amino acid causing change Arg419Gln located in exon
      13. Single SNP analysis indicated that allele 419Gln is associated with
      green/hazel iris colour (p < 0.001). According to tree scanning analysis, the
      proportion of eye colour variation explained by this nucleotide position is
      merely 4%. Thus, additional variation present in the OCA2 gene and perhaps some
      other pigment related genes must be taken into account in order to explain the
      high phenotypic variation in iris colour.

PMID- 18093282
TI  - Shared genomic segment analysis. Mapping disease predisposition genes in extended
      pedigrees using SNP genotype assays.
AB  - We examine the utility of high density genotype assays for predisposition gene
      localization using extended pedigrees. Results for the distribution of the number
      and length of genomic segments shared identical by descent among relatives
      previously derived in the context of genomic mismatch scanning are reviewed in
      the context of dense single nucleotide polymorphism maps. We use long runs of
      loci at which cases share a common allele identically by state to localize
      hypothesized predisposition genes. The distribution of such runs under the
      hypothesis of no genetic effect is evaluated by simulation. Methods are
      illustrated by analysis of an extended prostate cancer pedigree previously
      reported to show significant linkage to chromosome 1p23. Our analysis establishes
      that runs of simple single locus statistics can be powerful, tractable and robust
      for finding DNA shared between relatives, and that extended pedigrees offer
      powerful designs for gene detection based on these statistics.

PMID- 18093283
TI  - Spatial analysis and surname analysis: complementary tools for shedding light on
      human longevity patterns.
AB  - Starting from the observation that human longevity patterns show regional
      variations, we applied Spatial Analysis (using the Geographic Information System)
      and Surname Analysis to highlight the effect of the population genetic structure
      on such patterns. The study was carried out in Calabria, a southern Italian
      region which is characterized by a wide variability of geographic features (high
      mountains and deep valleys which created geographic isolates in the past). We
      identified three zones of high longevity: a male and a female longevity zone were
      located near the town of Cosenza (northern Calabria), while a male longevity zone
      was located in a mountainous and quite isolated part of the province of Reggio
      Calabria (southern Calabria). The latter zone was characterized by the lowest
      Female/Male ratio in nonagenarians observed to date. By applying surname analysis
      (Fisher's alpha) we found a significant negative correlation between surname
      abundance and index of longevity, showing that this isolated zone of male
      longevity presents a high level of inbreeding. On the whole, the results showed
      the effectiveness of spatial analysis in revealing geographical longevity
      patterns, and highlighted the importance of the population genetic structure in
      shaping such patterns.

PMID- 18093284
TI  - Testing for equality of standardized composite measures of linkage
      disequilibrium.
AB  - We described the approximate variance for a composite measure of linkage
      disequilibrium (LD), which depends only on genotype frequencies and allows for
      departure from Hardy-Weinberg disequilibrium (Hamilton et al. 2006). Here we
      extend this work to allow for inferences about differences in composite LD
      coefficients, as we illustrate with two examples. Simulations demonstrate
      consistency of type I error rates under most conditions. Calculations for power
      and sample size are also given.

PMID- 18093285
TI  - Prenatal stress and subsequent exposure to chronic mild stress influence
      dendritic spine density and morphology in the rat medial prefrontal cortex.
AB  - BACKGROUND: Both prenatal stress (PS) and postnatal chronic mild stress (CMS) are
      associated with behavioral and mood disturbances in humans and rodents. The aim
      of this study was to reveal putative PS- and/or CMS-related changes in basal
      spine morphology and density of pyramidal neurons in the rat medial prefrontal
      cortex (mPFC). RESULTS: We show that rats exposed to PS and/or CMS display
      changes in the morphology and number of basal spines on pyramidal neurons in the
      mPFC. CMS had a negative effect on spine densities, particularly on spines of the
      mushroom type, which are considered to form stronger and more stable synapses
      than other spine types. PS alone did not affect spine densities, but had a
      negative effect on the ratio of mushroom spines. In addition, PS seemed to make
      rats less responsive to some of the negative effects of CMS, which supports the
      notion that PS represents a predictive adaptive response. CONCLUSION: The
      observed changes may represent a morphological basis of PS- and CMS-related
      disturbances, and future studies in the field should not only consider total
      spine densities, but also separate between different spine types.

PMID- 18093286
TI  - Acute phase protein response in an experimental model of ovine caseous
      lymphadenitis.
AB  - BACKGROUND: Caseous lymphadenitis (CLA) is a disease of small ruminants caused by
      Corynebacterium pseudotuberculosis. The pathogenesis of CLA is a slow process,
      and produces a chronic rather than an acute disease state. Acute phase proteins
      (APP) such as haptoglobin (Hp) serum amyloid A (SAA) and alpha1 acid glycoprotein
      (AGP) are produced by the liver and released into the circulation in response to
      pro-inflammatory cytokines. The concentration of Hp in serum increases in
      experimental CLA but it is not known if SAA and AGP respond in parallel or have
      differing response profiles. RESULTS: The concentration in serum of Hp, SAA and
      AGP in 6 sheep challenged with 2 x 105 cells of C. pseudotuberculosis showed
      significant increases (P < 0.05) compared to 3 unchallenged control sheep. By day
      7 post infection. (p.i.) the Hp and SAA concentrations reached mean (+/- SEM)
      values of 1.65 +/- 0.21 g/L and 18.1 +/- 5.2 mg/L respectively. Thereafter, their
      concentrations fell with no significant difference to those of the control sheep
      by day 18 p.i.. In contrast, the serum AGP concentration in infected sheep
      continued to rise to a peak of 0.38 +/- 0.05 g/L on day 13 p.i., after which a
      slow decline occurred, although the mean concentration remained significantly
      higher (P < 0.05) than the control group up to 29 days p.i.. Specific IgG to
      phospholidase D of C. pseudotuberculosis became detectable at 11 days p.i. and
      continued to rise throughout the experiment. CONCLUSION: The serum concentrations
      of Hp, SAA and AGP were raised in sheep in an experimental model of CLA. An
      extended response was found for AGP which occurred at a point when the infection
      was likely to have been transforming from an acute to a chronic phase. The
      results suggest that AGP could have a role as a marker for chronic conditions in
      sheep.

PMID- 18093287
TI  - Serial Analysis of Gene Expression in Plasmodium berghei salivary gland
      sporozoites.
AB  - BACKGROUND: The invasion of Anopheles salivary glands by Plasmodium sporozoites
      is an essential step for transmission of the parasite to the vertebrate host.
      Salivary gland sporozoites undergo a developmental programme to express genes
      required for their journey from the site of the mosquito bite to the liver and
      subsequent invasion of, and development within, hepatocytes. A Serial Analysis of
      Gene Expression was performed on Anopheles gambiae salivary glands infected or
      not with Plasmodium berghei and we report here the analysis of the Plasmodium
      sporozoite transcriptome. RESULTS: Annotation of 530 tag sequences homologous to
      Plasmodium berghei genomic sequences identified 123 genes expressed in salivary
      gland sporozoites and these genes were classified according to their transcript
      abundance. A subset of these genes was further studied by quantitative PCR to
      determine their expression profiles. This revealed that sporozoites modulate
      their RNA amounts not only between the midgut and salivary glands, but also
      during their storage within the latter. Among the 123 genes, the expression of 66
      is described for the first time in sporozoites of rodent Plasmodium species.
      CONCLUSION: These novel sporozoite expressed genes, especially those expressed at
      high levels in salivary gland sporozoites, are likely to play a role in
      Plasmodium infectivity in the mammalian host.

PMID- 18093288
TI  - The effect of environmental change on vascular plant and cryptogam communities
      from the Falkland Islands and the Maritime Antarctic.
AB  - BACKGROUND: Antarctic terrestrial vegetation is subject to one of the most
      extreme climates on Earth. Currently, parts of Antarctica are one of the fastest
      warming regions on the planet. During 3 growing seasons, we investigated the
      effect of experimental warming on the diversity and abundance of coastal plant
      communities in the Maritime Antarctic region (cryptogams only) and the Falkland
      Islands (vascular plants only). We compared communities from the Falkland Islands
      (51 degrees S, mean annual temperature 7.9 degrees C), with those of Signy Island
      (60 degrees S, -2.1 degrees C) and Anchorage Island (67 degrees S, -2.6 degrees
      C), and experimental temperature manipulations at each of the three islands using
      Open Top Chambers (OTCs). RESULTS: Despite the strong difference in plant growth
      form dominance between the Falkland Islands and the Maritime Antarctic,
      communities across the gradient did not differ in total diversity and species
      number. During the summer months, the experimental temperature increase at 5 cm
      height in the vegetation was similar between the locations (0.7 degrees C across
      the study). In general, the response to this experimental warming was low. Total
      lichen cover showed a non-significant decreasing trend at Signy Island (p <
      0.06). In the grass community at the Falkland Islands total vegetation cover
      decreased more in the OTCs than in adjacent control plots, and two species
      disappeared within the OTCs after only two years. This was most likely a combined
      consequence of a previous dry summer and the increase in temperature caused by
      the OTCs. CONCLUSION: These results suggest that small temperature increases may
      rapidly lead to decreased soil moisture, resulting in more stressful conditions
      for plants. The more open plant communities (grass and lichen) appeared more
      negatively affected by such changes than dense communities (dwarf shrub and
      moss).

PMID- 18093289
TI  - The Internet for weight control in an obese sample: results of a randomised
      controlled trial.
AB  - BACKGROUND: Rising levels of obesity coupled with the limited success of
      currently available weight control methods highlight the need for investigation
      of novel approaches to obesity treatment. This study aims to determine the
      effectiveness and cost-effectiveness of an Internet-based resource for obesity
      management. METHODS: A randomised controlled trial conducted in a community
      setting, where obese volunteers (n = 221) were randomly assigned to Internet
      group (n = 111) or usual care group (n = 110). Objective measures of weight and
      height were obtained. Questionnaires were used to collect dietary, lifestyle,
      physical activity and quality of life data. Data were collected at baseline, six
      months and 12 months. RESULTS: Data were collected on 54 (49%) participants in
      the Internet group and 77 (70%) participants in the usual care group at 12
      months. Based on analysis conducted on all available data, the Internet group
      lost 1.3 kg, compared with 1.9 kg weight loss in the usual care group at 12
      months, a non-significant difference (difference = 0.6 kg; 95% CI: -1.4 to 2.5, p
      = 0.56). No significant differences in change in secondary outcome measures
      between the two groups at six or 12 months were revealed. Total costs per person
      per year were higher in the Internet group than the usual care group (
      pound992.40 compared to pound276.12), primarily due to the fixed costs associated
      with setting up the website, and QALYs were similar (0.78 and 0.77) for both
      groups. CONCLUSION: This trial failed to show any additional benefit of this
      website in terms of weight loss or secondary outcome measures compared with usual
      care. High attrition and low compliance limits the results of this research. The
      results suggest that the Internet-based weight control resource was not a cost
      effective tool for weight loss in the obese sample studied. TRIAL REGISTRATION:
      ISRCTN 58621669.

PMID- 18093290
TI  - Complex phylogeographic history of central African forest elephants and its
      implications for taxonomy.
AB  - BACKGROUND: Previous phylogenetic analyses of African elephants have included
      limited numbers of forest elephant samples. A large-scale assessment of
      mitochondrial DNA diversity in forest elephant populations here reveals a more
      complex evolutionary history in African elephants as a whole than two-taxon
      models assume. RESULTS: We analysed hypervariable region 1 of the mitochondrial
      control region for 71 new central African forest elephants and the mitochondrial
      cytochrome b gene from 28 new samples and compare these sequences to other
      African elephant data. We find that central African forest elephant populations
      fall into at least two lineages and that west African elephants (both forest and
      savannah) share their mitochondrial history almost exclusively with central
      African forest elephants. We also find that central African forest populations
      show lower genetic diversity than those in savannahs, and infer a recent
      population expansion. CONCLUSION: Our data do not support the separation of
      African elephants into two evolutionary lineages. The demographic history of
      African elephants seems more complex, with a combination of multiple refugial
      mitochondrial lineages and recurrent hybridization among them rendering a simple
      forest/savannah elephant split inapplicable to modern African elephant
      populations.

PMID- 18093291
TI  - A genome-wide scan for type 1 diabetes susceptibility genes in nuclear families
      with multiple affected siblings in Finland.
AB  - BACKGROUND: A genome-wide search for genes that predispose to type 1 diabetes
      using linkage analysis was performed using 900 microsatellite markers in 70
      nuclear families with affected siblings from Finland, a population expected to be
      more genetically homogeneous than others, and having the highest incidence of
      type 1 diabetes in the world and, yet, the highest proportion in Europe of cases
      (10%) carrying neither of the highest risk HLA haplotypes that include DR3 or DR4
      alleles. RESULTS: In addition to the evidence of linkage to the HLA region on
      6p21 (nominal p = 4.0 x 10-6), significant evidence of linkage in other
      chromosome regions was not detected with a single-locus analysis. The two-locus
      analysis conditional on the HLA gave a maximum lod score (MLS) of 3.1 (nominal p
      = 2 x 10-4) on chromosome 9p13 under an additive model; MLS of 2.1 (nominal p =
      6.1 x 10-3) on chromosome 17p12 and MLS of 2.5 (nominal p = 2.9 x 10-3) on
      chromosome 18p11 under a general model. CONCLUSION: Our genome scan data
      confirmed the primary contribution of the HLA genes also in the high-risk Finnish
      population, and suggest that non-HLA genes also contribute to the familial
      clustering of type 1 diabetes in Finland.

PMID- 18093292
TI  - Duffy blood group gene polymorphisms among malaria vivax patients in four areas
      of the Brazilian Amazon region.
AB  - BACKGROUND: Duffy blood group polymorphisms are important in areas where
      Plasmodium vivax predominates, because this molecule acts as a receptor for this
      protozoan. In the present study, Duffy blood group genotyping in P. vivax malaria
      patients from four different Brazilian endemic areas is reported, exploring
      significant associations between blood group variants and susceptibility or
      resistance to malaria. METHODS: The P. vivax identification was determined by non
      genotypic and genotypic screening tests. The Duffy blood group was genotyped by
      PCR/RFLP in 330 blood donors and 312 malaria patients from four Brazilian Amazon
      areas. In order to assess the variables significance and to obtain independence
      among the proportions, the Fisher's exact test was used. RESULTS: The data show a
      high frequency of the FYA/FYB genotype, followed by FYB/FYB, FYA/FYA, FYA/FYB-33
      and FYB/FYB-33. Low frequencies were detected for the FYA/FYX, FYB/FYX, FYX/FYX
      and FYB-33/FYB-33 genotypes. Negative Duffy genotype (FYB-33/FYB-33) was found in
      both groups: individuals infected and non-infected (blood donors). No individual
      carried the FYX/FYB-33 genotype. Some of the Duffy genotypes frequencies showed
      significant differences between donors and malaria patients. CONCLUSION: The
      obtained data suggest that individuals with the FYA/FYB genotype have higher
      susceptibility to malaria. The presence of the FYB-33 allele may be a selective
      advantage in the population, reducing the rate of infection by P. vivax in this
      region. Additional efforts may contribute to better elucidate the
      physiopathologic differences in this parasite/host relationship in regions
      endemic for P. vivax malaria, in particular the Brazilian Amazon region.

PMID- 18093293
TI  - TABASCO: A single molecule, base-pair resolved gene expression simulator.
AB  - BACKGROUND: Experimental studies of gene expression have identified some of the
      individual molecular components and elementary reactions that comprise and
      control cellular behavior. Given our current understanding of gene expression,
      and the goals of biotechnology research, both scientists and engineers would
      benefit from detailed simulators that can explicitly compute genome-wide
      expression levels as a function of individual molecular events, including the
      activities and interactions of molecules on DNA at single base pair resolution.
      However, for practical reasons including computational tractability, available
      simulators have not been able to represent genome-scale models of gene expression
      at this level of detail. RESULTS: Here we develop a simulator, TABASCO
      http://openwetware.org/wiki/TABASCO, which enables the precise representation of
      individual molecules and events in gene expression for genome-scale systems. We
      use a single molecule computational engine to track individual molecules
      interacting with and along nucleic acid polymers at single base resolution.
      Tabasco uses logical rules to automatically update and delimit the set of species
      and reactions that comprise a system during simulation, thereby avoiding the need
      for a priori specification of all possible combinations of molecules and reaction
      events. We confirm that single molecule, base-pair resolved simulation using
      TABASCO (Tabasco) can accurately compute gene expression dynamics and, moving
      beyond previous simulators, provide for the direct representation of
      intermolecular events such as polymerase collisions and promoter occlusion. We
      demonstrate the computational capacity of Tabasco by simulating the entirety of
      gene expression during bacteriophage T7 infection; for reference, the 39,937 base
      pair T7 genome encodes 56 genes that are transcribed by two types of RNA
      polymerases active across 22 promoters. CONCLUSION: Tabasco enables genome-scale
      simulation of transcription and translation at individual molecule and single
      base-pair resolution. By directly representing the position and activity of
      individual molecules on DNA, Tabasco can directly test the effects of detailed
      molecular processes on system-wide gene expression. Tabasco would also be useful
      for studying the complex regulatory mechanisms controlling eukaryotic gene
      expression. The computational engine underlying Tabasco could also be adapted to
      represent other types of processive systems in which individual reaction events
      are organized across a single spatial dimension (e.g., polysaccharide synthesis).

PMID- 18093294
TI  - Doloplus-2, a valid tool for behavioural pain assessment?
AB  - BACKGROUND: The Doloplus-2 is used for behavioural pain assessment in cognitively
      impaired patients. Little data exists on the psychometric properties of the
      Doloplus-2. Our objectives were to test the criterion validity and inter-rater
      reliability of the Doloplus-2, and to explore a design for validations of
      behavioural pain assessment tools. METHODS: Fifty-one nursing home patients and
      22 patients admitted to a geriatric hospital ward were included. All were
      cognitively impaired and unable to self-report pain. Each patient was examined by
      an expert in pain evaluation and treatment, who rated the pain on a numerical
      rating scale. The ratings were based on information from the medical record,
      reports from nurses and patients (if possible) about pain during the past 24
      hours, and a clinical examination. These ratings were used as pain criterion. The
      Doloplus-2 was administered by the attending nurse. Regression analyses were used
      to estimate the ability of the Doloplus-2 to explain the expert's ratings. The
      inter-rater reliability of the Doloplus-2 was evaluated in 16 patients by
      comparing the ratings of two nurses administrating the Doloplus-2. RESULTS: There
      was no association between the Doloplus-2 and the expert's pain ratings (R2 =
      0.02). There was an association (R2 = 0.54) between the expert's ratings and the
      Doloplus-2 scores in a subgroup of 16 patients assessed by a geriatric expert
      nurse (the most experienced Doloplus-2 administrator). The inter-rater
      reliability between the Doloplus-2 administrators assessed by the intra-class
      coefficient was 0.77. The pain expert's ratings were compared with ratings of two
      independent geriatricians in a sub sample of 15, and were found satisfactory
      (intra-class correlation 0.74). CONCLUSION: It was challenging to conduct such a
      study in patients with cognitive impairment and the study has several
      limitations. The results do not support the validity of the Doloplus-2 in its
      present version and they indicate that it demands specific administration skills.

PMID- 18093295
TI  - Detection of non-ST-elevation myocardial infarction and unstable angina in the
      acute setting: meta-analysis of diagnostic performance of multi-detector computed
      tomographic angiography.
AB  - BACKGROUND: Multi-detector computed tomography angiography (MDCTA) has been
      increasingly used in the evaluation of the coronary arteries. The purpose of this
      study was to review the literature on the diagnostic performance of MDCTA in the
      acute setting, for the detection of non-ST-elevation myocardial infarction
      (NSTEMI) and unstable angina pectoris (UAP). METHODS: A Pubmed and manual search
      of the literature published between January 2000 and June 2007 was performed.
      Studies were included that compared MDCTA with clinical outcome and/or CA in
      patients with acute chest pain, presenting at the emergency department. More
      specifically, studies that only included patients with initially negative cardiac
      enzymes suspected of having NSTEMI or UAP were included. Summary estimates of
      diagnostic odds ratio (DOR), sensitivity and specificity, negative (NLR) and
      positive likelihood ratio (PLR) were calculated on a patient basis. Random
      effects models and summary receiver operating curve (SROC) analysis were used to
      assess the diagnostic performance of MDCTA with 4 detectors or more. The
      proportion of non assessable scans (NAP) on MDCTA was also evaluated. In
      addition, the influence of study characteristics of each study on diagnostic
      performance and NAP was investigated with multivariable logistic regression.
      RESULTS: Nine studies totalling 566 patients, were included in the meta-analysis:
      one randomised trial and eight prospective cohort studies. Five studies on 64
      detector MDCTA and 4 studies on MDCTA with less than 64 detectors were included
      (32 detectors n = 1, 16 detectors n = 2, 16 and 4 detectors n = 1). Pooled DOR
      was 131.81 (95%CI, 50.90-341.31). The pooled sensitivity and specificity were
      0.95 (95%CI, 0.90-0.98) and 0.90 (95%CI, 0.87-0.93). The pooled NLR and PLR were
      0.12 (95%CI, 0.06-0.21) and 8,60 (95%CI, 5.03-14,69).The results of the logistic
      regressions showed that none of the investigated variables had influence on the
      diagnostic performance or NAP CONCLUSION: MDCTA of the coronary arteries performs
      good to excellent in the diagnosis of coronary artery disease in the acute
      setting and it can be used for early exclusion of NSTEMI or UAP in patients in
      the emergency department.

PMID- 18093297
TI  - The effects of Rhizoma Curculiginis and Rhizoma Drynariae extracts on bones.
AB  - BACKGROUND: Rhizoma Curculiginis (Xianmao) and Rhizoma Drynariae (Gusuibu) are
      'Yang-tonifying' traditional Chinese herbal medicines used to strengthen bones.
      This investigation aims to assess the systemic effect of extracts of Rhizoma
      Curculiginis and Rhizoma Drynariae on bone histomorphology and formation, and
      their local effect on bone healing. METHODS: For the investigation of the
      systemic effect, thirty 8-week-old male BALB/c mice were divided into three
      groups: (1) control group, ten mice fed daily with distilled water; (2) Rhizoma
      Curculiginis group, ten mice fed daily with distilled water mixed with Rhizoma
      Curculiginis extract; (3) Rhizoma Drynarie group, ten mice fed daily with
      distilled water mixed with Rhizoma Drynarie extract. The mice were fed for five
      weeks before sacrifice. Twenty micro-tomographic slices with an increment of 0.25
      mm were prepared to cover the proximal end of the left tibia of each mouse.
      Quantitative morphometry of the bone structure was performed. For the
      investigation of the local effect on bone healing, two bone defects (5 x 10 mm)
      were created in the parietal bone of each of the three New Zealand white rabbits.
      Two defects in the first animal were grafted with collagen matrix with Rhizoma
      Curculiginis extract; two defects in the second animal were grafted with collagen
      matrix with Rhizoma Drynarie extract; two defects in the third (control) animal
      were grafted with collagen matrix alone. The animals were sacrificed on day 14
      and the defects were dissected and prepared for histological and ultrastructural
      assessment. RESULTS: Rhizoma Curculiginis and Rhizoma Drynariae extracts altered
      the bone histomorphology, both increasing the trabecular number by 10% (P =
      0.002). Rhizoma Curculiginis extract increased bone density by 3.13% (P = 0.122)
      and Rhizoma Drynariae extract increased bone density by 6.45% (P = 0.005). Both
      Rhizoma Curculiginis and Rhizoma Drynariae extracts induced new bone formation on
      the margins of the defects. CONCLUSION: Two 'Yang-tonifying' herbs, Rhizoma
      Curculiginis and Rhizoma Drynariae, were demonstrated to have systemic effects on
      bone histomorphology and formation as well as local bone healing.

PMID- 18093296
TI  - Inducible nitric oxide synthase, Nos2, does not mediate optic neuropathy and
      retinopathy in the DBA/2J glaucoma model.
AB  - BACKGROUND: Nitric oxide synthase 2 (NOS2) contributes to neural death in some
      settings, but its role in glaucoma remains controversial. NOS2 is implicated in
      retinal ganglion cell degeneration in a rat glaucoma model in which intraocular
      pressure (IOP) is experimentally elevated by blood vessel cauterization, but not
      in a rat glaucoma model where IOP was elevated by injection of hypertonic saline.
      To test the importance of NOS2 for an inherited glaucoma, in this study we both
      genetically and pharmacologically decreased NOS2 activity in the DBA/2J mouse
      glaucoma model. METHODS: The expression of Nos2 in the optic nerve head was
      analyzed at both the RNA and protein levels at different stages of disease
      pathogenesis. To test the involvement of Nos2 in glaucomatous neurodegeneration,
      a null allele of Nos2 was backcrossed into DBA/2J mice and the incidence and
      severity of glaucoma was assessed in mice of each Nos2 genotype. Additionally,
      DBA/2J mice were treated with the NOS2 inhibitor aminoguanidine and the disease
      compared to untreated mice. RESULTS: Optic nerve head Nos2 RNA levels varied and
      increased during moderate but decreased at early and severe stages of disease.
      Despite the presence of a few NOS2 positive cells in the optic nerve head, NOS2
      protein was not substantially increased during the glaucoma. Genetic deficiency
      of Nos2 or aminoguanidine treatment did not alter the IOP profile of DBA/2J mice.
      Additionally, neither Nos2 deficiency nor aminoguanidine had any detectable
      affect on the glaucomatous optic nerve damage. CONCLUSION: Glaucomatous
      neurodegeneration in DBA/2J mice does not require NOS2 activity. Further
      experiments involving various models are needed to assess the general importance
      of Nos2 in glaucoma.

PMID- 18093298
TI  - Passive movement therapy in patients with moderate to severe paratonia; study
      protocol of a randomised clinical trial (ISRCTN43069940).
AB  - BACKGROUND: Paratonia, a form of hypertonia, is associated with loss of mobility
      and with the development of contractures especially in the late stages of the
      dementia. Passive movement therapy (PMT) currently is the main physiotherapeutic
      intervention. General doubt about the beneficial effects of this widely used
      therapy necessitates a randomised clinical trial (RCT) to study the efficacy of
      PMT on the severity of paratonia and on the improvement of daily care.
      METHODS/DESIGN: A RCT with a 4-week follow-up period. Patients with dementia
      (according to the DSM-IV-TR Criteria) and moderate to severe paratonia are
      included in the study after proxy consent. By means of computerised and concealed
      block randomisation (block-size of 4) patients are included in one of two groups.
      The first group receives PMT, the second group receives usual care without PMT.
      PMT is given according to a protocol by physical therapist three times a week for
      four weeks in a row. The severity of paratonia (Modified Ashworth scale), the
      severity of the dementia (Global Deterioration Scale), the clinical improvement
      (Clinical Global Impressions), the difficulty in daily care (Patient Specific
      Complaints) and the experienced pain in daily care of the participant (PACSLAC-D)
      is assessed by assessors blind to treatment allocation at baseline, after 6 and
      12 treatments. Success of the intervention is defined as a significant increase
      of decline on the modified Ashworth scale. The 'proportion of change' in two and
      four weeks time on this scale will be analysed. Also a multiple logistic
      regression analysis using declined/not declined criteria as dependent variable
      with correction for relevant confounders (e.g. stage of dementia, medication, co
      morbidity) will be used. DISCUSSION: This study is the first RCT of this size to
      gain further insight on the effect of passive movement therapy on the severity of
      paratonia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43069940.

PMID- 18093299
TI  - The PRICE study (Protection Rest Ice Compression Elevation): design of a
      randomised controlled trial comparing standard versus cryokinetic ice
      applications in the management of acute ankle sprain [ISRCTN13903946].
AB  - BACKGROUND: Cryotherapy (the application of ice for therapeutic purposes) is one
      of the most common treatment modalities employed in the immediate management of
      acute soft tissue injury. Despite its widespread clinical use, the precise
      physiological responses to therapeutic cooling have not been fully elucidated,
      and effective evidence-based treatment protocols are yet to be established.
      Intermittent ice applications are thought to exert a significant analgesic
      effect. This could facilitate earlier therapeutic exercise after injury,
      potentially allowing for a quicker return to activity. The primary aim of the
      forthcoming study is therefore to examine the safety and effectiveness of
      combining intermittent ice applications with periods of therapeutic exercise in
      the first week after an acute ankle sprain. METHODS/DESIGN: The study is a
      randomised controlled trial. 120 subjects with an acute grade I or grade II ankle
      sprain will be recruited from Accident & Emergency and a University based Sports
      Injury Clinic. Subjects will be randomised under strict double-blind conditions
      to either a standard cryotherapy (intermittent ice applications with compression)
      or cryokinetic treatment group (intermittent ice applications with compression
      and therapeutic exercise). After the first week, treatment will be standardised
      across groups. Assessor blinding will be maintained throughout the trial. Primary
      outcome will be function, assessed using the Lower Extremity Functional Scale
      (LEFS). Additional outcomes will include pain (10 cm Visual Analogue Scale),
      swelling (modified figure-of-eight method) and activity levels (activPALtrade
      mark physical activity monitor, PAL Technologies, Glasgow, UK). Diagnostic
      Ultrasound (Episcan-1-200 high frequency ultrasound scanning system, Longport
      International Ltd, PA) will also be used to assess the degree of soft tissue
      injury. After baseline assessment subjects will be followed up at 1, 2, 3 & 4
      weeks post injury. All data will be analysed using repeated measures analysis of
      co-variance (ANCOVA). DISCUSSION: This paper describes the rationale and design
      of a randomised controlled trial which will examine the effectiveness of two
      different cryotherapy protocols in the early management of acute ankle sprain.
      TRIAL REGISTRATION: ISRCTN13903946.

PMID- 18093300
TI  - Assessment of the alveolar volume when sampling exhaled gas at different expired
      volumes in the single breath diffusion test.
AB  - BACKGROUND: Alveolar volume measured according to the American Thoracic Society
      European Respiratory Society (ATS-ERS) guidelines during the single breath
      diffusion test can be underestimated when there is maldistribution of
      ventilation. Therefore, the alveolar volume calculated by taking into account the
      ATS-ERS guidelines was compared to the alveolar volume measured from
      sequentiallly collected samples of the expired volume in two groups of
      individuals: COPD patients and healthy individuals. The aim of this study was to
      investigate the effects of the maldistribution of ventilation on the real
      estimate of alveolar volume and to evaluate some indicators suggestive of the
      presence of maldistribution of ventilation. METHODS: Thirty healthy individuals
      and fifty patients with moderate-severe COPD were studied. The alveolar volume
      was measured either according to the ATS-ERS guidelines or considering the whole
      expired volume subdivided into five quintiles. An index reflecting the non
      uniformity of the distribution of ventilation was then derived (DeltaVA/VE).
      RESULTS: Significant differences were found when comparing the two measurements
      and the alveolar volume by quintiles appeared to have increased progressively
      towards residual volume in healthy individuals and much more in COPD patients.
      Therefore, DeltaVA/VE resulted in an abnormal increase in COPD. CONCLUSION: The
      results of our study suggest that the alveolar volume during the single breath
      diffusion test should be measured through the collection of a sample of expired
      volume which could be more representative of the overall gas composition,
      especially in the presence of uneven distribution of ventilation. Further studies
      aimed at clarifying the final effects of this way of calculating the alveolar
      volume on the measure of DLCO are needed. DeltaVA/VE is an index that can help
      assess the severity of inhomogeneity in COPD patients.

PMID- 18093301
TI  - The first trimester human trophoblast cell line ACH-3P: a novel tool to study
      autocrine/paracrine regulatory loops of human trophoblast subpopulations--TNF
      alpha stimulates MMP15 expression.
AB  - BACKGROUND: The trophoblast compartment of the placenta comprises various
      subpopulations with distinct functions. They interact among each other by
      secreted signals thus forming autocrine or paracrine regulatory loops. We
      established a first trimester trophoblast cell line (ACH-3P) by fusion of primary
      human first trimester trophoblasts (week 12 of gestation) with a human
      choriocarcinoma cell line (AC1-1). RESULTS: Expression of trophoblast markers
      (cytokeratin-7, integrins, matrix metalloproteinases), invasion abilities and
      transcriptome of ACH-3P closely resembled primary trophoblasts. Morphology,
      cytogenetics and doubling time was similar to the parental AC1-1 cells. The
      different subpopulations of trophoblasts e.g., villous and extravillous
      trophoblasts also exist in ACH-3P cells and can be immuno-separated by HLA-G
      surface expression. HLA-G positive ACH-3P display pseudopodia and a stronger
      expression of extravillous trophoblast markers. Higher expression of insulin-like
      growth factor II receptor and human chorionic gonadotropin represents the basis
      for the known autocrine stimulation of extravillous trophoblasts. CONCLUSION: We
      conclude that ACH-3P represent a tool to investigate interaction of syngeneic
      trophoblast subpopulations. These cells are particularly suited for studies into
      autocrine and paracrine regulation of various aspects of trophoblast function. As
      an example a novel effect of TNF-alpha on matrix metalloproteinase 15 in HLA-G
      positive ACH-3P and explants was found.

PMID- 18093303
TI  - Adaptive dynamic resource allocation in annual eusocial insects: environmental
      variation will not necessarily promote graded control.
AB  - BACKGROUND: According to the classical model of Macevicz and Oster, annual
      eusocial insects should show a clear dichotomous "bang-bang" strategy of resource
      allocation; colony fitness is maximised when a period of pure colony growth
      (exclusive production of workers) is followed by a single reproductive period
      characterised by the exclusive production of sexuals. However, in several species
      graded investment strategies with a simultaneous production of workers and
      sexuals have been observed. Such deviations from the "bang-bang" strategy are
      usually interpreted as an adaptive (bet-hedging) response to environmental
      fluctuations such as variation in season length or food availability. To generate
      predictions about the optimal investment pattern of insect colonies in
      fluctuating environments, we slightly modified Macevicz and Oster's classical
      model of annual colony dynamics and used a dynamic programming approach nested
      into a recurrence procedure for the solution of the stochastic optimal control
      problem. RESULTS: 1) The optimal switching time between pure colony growth and
      the exclusive production of sexuals decreases with increasing environmental
      variance. 2) Yet, for reasonable levels of environmental fluctuations no
      deviation from the typical bang-bang strategy is predicted. 3) Model calculations
      for the halictid bee Lasioglossum malachurum reveal that bet-hedging is not
      likely to be the reason for the graded allocation into sexuals versus workers
      observed in this species. 4) When environmental variance reaches a critical level
      our model predicts an abrupt change from dichotomous behaviour to graded
      allocation strategies, but the transition between colony growth and production of
      sexuals is not necessarily monotonic. Both, the critical level of environmental
      variance as well as the characteristic pattern of resource allocation strongly
      depend on the type of function used to describe environmental fluctuations.
      CONCLUSION: Up to now bet-hedging as an evolutionary response to variation in
      season length has been the main argument to explain field observations of graded
      resource allocation in annual eusocial insect species. However, our model shows
      that the effect of moderate fluctuations of environmental conditions does not
      select for deviation from the classical bang-bang strategy and that the evolution
      of graded allocation strategies can be triggered only by extreme fluctuations.
      Detailed quantitative observations on resource allocation in eusocial insects are
      needed to analyse the relevance of alternative explanations, e.g. logistic colony
      growth or reproductive conflict between queen and workers, for the evolution of
      graded allocation strategies.

PMID- 18093302
TI  - Effective transcription factor binding site prediction using a combination of
      optimization, a genetic algorithm and discriminant analysis to capture distant
      interactions.
AB  - BACKGROUND: Reliable transcription factor binding site (TFBS) prediction methods
      are essential for computer annotation of large amount of genome sequence data.
      However, current methods to predict TFBSs are hampered by the high false-positive
      rates that occur when only sequence conservation at the core binding-sites is
      considered. RESULTS: To improve this situation, we have quantified the
      performance of several Position Weight Matrix (PWM) algorithms, using exhaustive
      approaches to find their optimal length and position. We applied these approaches
      to bio-medically important TFBSs involved in the regulation of cell growth and
      proliferation as well as in inflammatory, immune, and antiviral responses (NF
      kappaB, ISGF3, IRF1, STAT1), obesity and lipid metabolism (PPAR, SREBP, HNF4),
      regulation of the steroidogenic (SF-1) and cell cycle (E2F) genes expression. We
      have also gained extra specificity using a method, entitled SiteGA, which takes
      into account structural interactions within TFBS core and flanking regions, using
      a genetic algorithm (GA) with a discriminant function of locally positioned
      dinucleotide (LPD) frequencies. To ensure a higher confidence in our approach, we
      applied resampling-jackknife and bootstrap tests for the comparison, it appears
      that, optimized PWM and SiteGA have shown similar recognition performances. Then
      we applied SiteGA and optimized PWMs (both separately and together) to sequences
      in the Eukaryotic Promoter Database (EPD). The resulting SiteGA recognition
      models can now be used to search sequences for BSs using the web tool, SiteGA.
      Analysis of dependencies between close and distant LPDs revealed by SiteGA models
      has shown that the most significant correlations are between close LPDs, and are
      generally located in the core (footprint) region. A greater number of less
      significant correlations are mainly between distant LPDs, which spanned both core
      and flanking regions. When SiteGA and optimized PWM models were applied together,
      this substantially reduced false positives at least at higher stringencies.
      CONCLUSION: Based on this analysis, SiteGA adds substantial specificity even to
      optimized PWMs and may be considered for large-scale genome analysis. It adds to
      the range of techniques available for TFBS prediction, and EPD analysis has led
      to a list of genes which appear to be regulated by the above TFs.

PMID- 18093304
TI  - Measuring the effect of intimate partner violence on health-related quality of
      life: a qualitative focus group study.
AB  - BACKGROUND: Health related quality of life (HRQOL) can be measured by a wide
      range of instruments, many of which have been designed for specific conditions or
      uses. "Preference-based" measures assess the value individuals place on health,
      and are included in economic evaluations of treatments and interventions (such as
      cost effectiveness analysis). As economic evaluation becomes more common, it is
      important to assess the applicability of preference-based health related quality
      of life (HRQOL) measures to public health issues. This study investigated the
      usefulness of such instruments in the context of intimate partner violence (IPV),
      a public health concern that that can seriously affect quality of life. METHODS:
      The study consisted of focus groups with abused women to determine the aspects of
      life affected by IPV, and an analysis of existing HRQOL measures. Eight focus
      groups (n = 40) were conducted in which participants discussed the domains of
      health affected by IPV. Results were content analyzed and compared with the
      domains of health included in four commonly-used, preference-based HRQOL
      measures. RESULTS: The average focus group participant was 43 years old,
      unemployed, African American, with 3 children. Domains of health reported to be
      affected by IPV included physical functioning, emotional and psychological
      functioning, social functioning and children's functioning. Psychological health
      was the most severely affected domain. The Short Form 36, the Health Utilities
      Index, the EuroQol 5D, and the Quality of Well-being Scale were found to vary in
      the degree to which they include domains of health important in IPV.
      Psychological health is included to a limited extent, and the spill-over effect
      of a condition on other family members, including children, is not included at
      all. CONCLUSION: Emotional and psychological health plays an important role in
      the overall HRQOL of abused women but is relatively underemphasized in preference
      based HRQOL measures. This may lead to an underestimation of the impact of
      partner violence on HRQOL when using these measures and in economic evaluations
      that rely thereon. Holistic measurement approaches or expanded measures that
      capture the far-reaching effects of IPV on HRQOL may be needed to accurately
      measure the effect of this condition on women's health.

PMID- 18093305
TI  - Retinoic acid is a potential dorsalising signal in the late embryonic chick
      hindbrain.
AB  - BACKGROUND: Human retinoic acid teratogenesis results in malformations of
      dorsally derived hindbrain structures such as the cerebellum, noradrenergic
      hindbrain neurons and the precerebellar system. These structures originate from
      the rhombic lip and adjacent dorsal precursor pools that border the fourth
      ventricle roofplate. While retinoic acid synthesis is known to occur in the
      meninges that blanket the hindbrain, the particular sensitivity of only dorsal
      structures to disruptions in retinoid signalling is puzzling. We therefore looked
      for evidence within the neural tube for more spatiotemporally specific signalling
      pathways using an in situ hybridisation screen of known retinoic acid pathway
      transcripts. RESULTS: We find that there are highly restricted domains of
      retinoic acid synthesis and breakdown within specific hindbrain nuclei as well as
      the ventricular layer and roofplate. Intriguingly, transcripts of cellular
      retinoic acid binding protein 1 are always found at the interface between
      dividing and post-mitotic cells. By contrast to earlier stages of development,
      domains of synthesis and breakdown in post-mitotic neurons are co-localised. At
      the rhombic lip, expression of the mRNA for retinoic acid synthesising and
      catabolising enzymes is spatially highly organised with respect to the Cath1
      positive precursors of migratory precerebellar neurons. CONCLUSION: The late
      developing hindbrain shows patterns of retinoic acid synthesis and use that are
      distinct from the well characterised phase of rostrocaudal patterning. Selected
      post-mitotic populations, such as the locus coeruleus, appear to both make and
      break down retinoic acid suggesting that a requirement for an autocrine, or at
      least a highly localised paracrine signalling network, might explain its acute
      sensitivity to retinoic acid disruption. At the rhombic lip, retinoic acid is
      likely to act as a dorsalising factor in parallel with other roofplate signalling
      pathways. While its precise role is unclear, retinoic acid is potentially well
      placed to regulate temporally determined cell fate decisions within the rhombic
      lip precursor pool.

PMID- 18093306
TI  - Identifying protein complexes directly from high-throughput TAP data with Markov
      random fields.
AB  - BACKGROUND: Predicting protein complexes from experimental data remains a
      challenge due to limited resolution and stochastic errors of high-throughput
      methods. Current algorithms to reconstruct the complexes typically rely on a two
      step process. First, they construct an interaction graph from the data,
      predominantly using heuristics, and subsequently cluster its vertices to identify
      protein complexes. RESULTS: We propose a model-based identification of protein
      complexes directly from the experimental observations. Our model of protein
      complexes based on Markov random fields explicitly incorporates false negative
      and false positive errors and exhibits a high robustness to noise. A model-based
      quality score for the resulting clusters allows us to identify reliable
      predictions in the complete data set. Comparisons with prior work on reference
      data sets shows favorable results, particularly for larger unfiltered data sets.
      Additional information on predictions, including the source code under the GNU
      Public License can be found at
      http://algorithmics.molgen.mpg.de/Static/Supplements/ProteinComplexes.
      CONCLUSION: We can identify complexes in the data obtained from high-throughput
      experiments without prior elimination of proteins or weak interactions. The few
      parameters of our model, which does not rely on heuristics, can be estimated
      using maximum likelihood without a reference data set. This is particularly
      important for protein complex studies in organisms that do not have an
      established reference frame of known protein complexes.

PMID- 18093307
TI  - Wellness through a comprehensive yogic breathing program - a controlled pilot
      trial.
AB  - BACKGROUND: Increasing rates of psychosocial disturbances give rise to increased
      risks and vulnerability for a wide variety of stress-related chronic pain and
      other illnesses. Relaxation exercises aim at reducing stress and thereby help
      prevent these unwanted outcomes. One of the widely used relaxation practices is
      yoga and yogic breathing exercises. One specific form of these exercises is
      Sudarshan Kriya and related practices (SK&P) which are understood to have
      favourable effects on the mind-body system. The goal of this pilot study was to
      design a protocol that can investigate whether SK&P can lead to increased feeling
      of wellness in healthy volunteers. METHODS: Participants were recruited in a
      small university city in Sweden and were instructed in a 6-day intensive program
      of SK&P which they practiced daily for six weeks. The control group was
      instructed to relax in an armchair each day during the same period. Subjects
      included a total of 103 adults, 55 in the intervention (SK&P) group and 48 in the
      control group. Various instruments were administered before and after the
      intervention. Hospital Anxiety Depression Scale measured the degree of anxiety
      and depression, Life Orientation Test measured dispositional optimism, Stress and
      Energy Test measured individual's energy and stress experiences. Experienced
      Deviation from Normal State measured the experience of altered state of
      consciousness. RESULTS: There were no safety issues. Compliance was high (only 1
      dropout in the SK&P group, and 5 in the control group). Outcome measures appeared
      to be appropriate for assessing the differences between the groups. Subjective
      reports generally correlated with the findings from the instruments. The data
      suggest that participants in the SK&P group, but not the control group, lowered
      their degree of anxiety, depression and stress, and also increased their degree
      of optimism (ANOVA; p < 0.001). The participants in the yoga group experienced
      the practices as a positive event that induced beneficial effects. CONCLUSION:
      These data indicate that the experimental protocol that is developed here is
      safe, compliance level is good, and a full scale trial is feasible. The data
      obtained suggest that adult participants may improve their wellness by learning
      and applying a program based on yoga and yogic breathing exercises; this can be
      conclusively assessed in a large-scale trial. TRIAL REGISTRATION: Australian
      Clinical Trial Registry ACTRN012607000175471.

PMID- 18093308
TI  - Crystallographic characterization of two novel crystal forms of human insulin
      induced by chaotropic agents and a shift in pH.
AB  - BACKGROUND: Insulin is a therapeutic protein that is widely used for the
      treatment of diabetes. Its biological function was discovered more than 80 years
      ago and it has since then been characterized extensively. Crystallization of the
      insulin molecule has always been a key activity since the protein is often
      administered by subcutaneous injections of crystalline insulin formulations. Over
      the years, insulin has been crystallized and characterized in a number of crystal
      systems. RESULTS: Interestingly, we have now discovered two new crystal forms of
      human insulin. The crystals were obtained when the two chaotropic agents, urea
      and thiocyanate were present in the crystallization experiments, and their
      structures were determined by X-ray crystallography. The crystals belong to the
      orthorhombic and monoclinic crystal systems, with space groups C2221 and C2
      respectively. The orthorhombic crystals were obtained at pH 6.5 and contained
      three insulin hexamers in R6 conformation in the asymmetric unit whilst the
      monoclinic C2 crystals were obtained at pH 7.0 and contained one R6 hexamer in
      the asymmetric unit. Common for the two new crystals is a hexamer-hexamer
      interaction that has not been found in any of the previous crystal forms of
      insulin. The contacts involve a tight glutamate-glutamate interaction with a
      distance of 2.3 A between groups. The short distance suggests a low barrier
      hydrogen bond. In addition, two tyrosine-tyrosine interactions occupying a known
      phenol binding pocket contribute to the stabilization of the contacts. Within the
      crystals, distinct binding sites for urea were found, adding further to the
      discussion on the role of urea in protein denaturation. CONCLUSION: The change in
      space group from C2221 to C2 was primarily caused by an increase in pH. The fewer
      number of hexamer-hexamer interactions comprising the short hydrogen bond in the
      C2 space group suggest that pH is the driving force. In addition, the distance
      between the two glutamates increases from 2.32 A in the C2221 crystals to 2.4 A
      in the C2 crystals. However, in both cases the low barrier hydrogen bond and the
      tyrosine-tyrosine interaction should contribute to the stability of the crystals
      which is crucial when used in pharmaceutical formulations.

PMID- 18093309
TI  - Post-traumatic upper cervical subluxation visualized by MRI: a case report.
AB  - BACKGROUND: This paper describes MRI findings of upper cervical subluxation due
      to alar ligament disruption following a vehicular collision. Incidental findings
      included the presence of a myodural bridge and a spinal cord syrinx. Chiropractic
      management of the patient is discussed. CASE PRESENTATION: A 21-year old female
      presented with complaints of acute, debilitating upper neck pain with unremitting
      sub-occipital headache and dizziness following a vehicular collision. Initial
      emergency department and neurologic investigations included x-ray and CT
      evaluation of the head and neck. Due to persistent pain, the patient sought
      chiropractic care. MRI of the upper cervical spine revealed previously
      unrecognized clinical entities. CONCLUSION: This case highlights the
      identification of upper cervical ligamentous injury that produced vertebral
      subluxation following a traumatic incident. MRI evaluation provided visualization
      of previously undetected injury. The patient experienced improvement through
      chiropractic care.

PMID- 18093310
TI  - Physical activity as a mediator of the impact of chronic conditions on quality of
      life in older adults.
AB  - BACKGROUND: Chronic conditions could negatively affect the quality of life of
      older adults. This may be partially due to a relative lack of physical activity.
      We examined whether physical activity mediates the relationship between different
      chronic conditions and several health outcomes that are important to the quality
      of life of older adults. METHODS: The data were taken from the Canadian Community
      Health Survey (cycle 1.1), a cross-section survey completed in 2001. Only
      respondents who were 65 years or older were included in our study (N = 22,432).
      The Health Utilities Index Mark 3 (HUI3) was used to measure overall quality of
      life, and to measure selected health outcomes (dexterity, mobility, pain,
      cognition, and emotional wellbeing) that are considered to be of importance to
      the quality of life of older adults. Leisure-time physical activity was assessed
      by determining weekly energy expenditure (Kcal per week) based on the metabolic
      equivalents of self-reported leisure activities. Linear and logistic regression
      models were used to determine the mediating effect of leisure-time physical
      activity while controlling for demographic variables (age and sex), substance use
      (tobacco use and alcohol consumption), and obesity. RESULTS: Having a chronic
      condition was associated with a relative decrease in health utility scores and a
      relative increase in mobility limitations, dexterity problems, pain, emotional
      problems (i.e., decreased happiness), and cognitive limitations. These negative
      consequences could be partially attributed to a relative lack of physical
      activity in older adults with a chronic condition (14% mediation for the HUI3
      score). The corresponding degree of mediation was 18% for mobility limitations,
      5% for pain, and 13% for emotional wellbeing (statistically significant mediation
      was not observed for the other health attributes). These values varied with
      respect to the different chronic conditions examined in our study. CONCLUSION:
      Older adults with chronic conditions are less likely to engage in leisure-time
      physical activities of at least 1,000 Kcal per week, and this association
      partially accounts for some negative consequences of chronic conditions,
      including mobility limitations, pain, and emotional problems. These findings
      provide support for health promotion programs that facilitate or encourage
      increased leisure-time physical activity in older people with chronic conditions.

PMID- 18093311
TI  - Quantitative determination by real-time PCR of four vaginal Lactobacillus
      species, Gardnerella vaginalis and Atopobium vaginae indicates an inverse
      relationship between L. gasseri and L. iners.
AB  - BACKGROUND: Most studies of the vaginal microflora have been based on culture or
      on qualitative molecular techniques. Here we applied existing real-time PCR
      formats for Lactobacillus crispatus, L. gasseri and Gardnerella vaginalis and
      developed new formats for Atopobium vaginae, L. iners and L. jensenii to obtain a
      quantitative non culture-based determination of these species in 71 vaginal
      samples from 32 pregnant and 28 non-pregnant women aged between 18 and 45 years.
      RESULTS: The 71 vaginal microflora samples of these women were categorized, using
      the Ison and Hay criteria, as refined by Verhelst et al. (2005), as follows:
      grade Ia: 8 samples, grade Iab: 10, grade Ib: 13, grade I-like: 10, grade II: 11,
      grade III: 12 and grade IV: 7.L. crispatus was found in all but 5 samples and was
      the most frequent Lactobacillus species detected. A significantly lower
      concentration of L. crispatus was found in grades II (p < 0.0001) and III (p =
      0.002) compared to grade I. L. jensenii was found in all grades but showed higher
      concentration in grade Iab than in grade Ia (p = 0.024). A. vaginae and G.
      vaginalis were present in high concentrations in grade III, with log10 median
      concentrations (log10 MC), respectively of 9.0 and 9.2 cells/ml. Twenty (38.5%)
      of the 52 G. vaginalis positive samples were also positive for A. vaginae. In
      grade II we found almost no L. iners (log10 MC: 0/ml) but a high concentration of
      L. gasseri (log10 MC: 8.7/ml). By contrast, in grade III we found a high
      concentration of L. iners (log10 MC: 8.3/ml) and a low concentration of L.
      gasseri (log10 MC: 0/ml). These results show a negative association between L.
      gasseri and L. iners (r = -0.397, p = 0.001) and between L. gasseri and A.
      vaginae (r = -0.408, p < 0.0001). CONCLUSION: In our study we found a clear
      negative association between L. iners and L. gasseri and between A. vaginae and
      L. gasseri. Our results do not provide support for the generally held proposition
      that grade II is an intermediate stage between grades I and III, because L.
      gasseri, abundant in grade II is not predominant in grade III, whereas L. iners,
      abundant in grade III is present only in low numbers in grade II samples.

PMID- 18093312
TI  - The development of a theory-based intervention to promote appropriate disclosure
      of a diagnosis of dementia.
AB  - BACKGROUND: The development and description of interventions to change
      professional practice are often limited by the lack of an explicit theoretical
      and empirical basis. We set out to develop an intervention to promote appropriate
      disclosure of a diagnosis of dementia based on theoretical and empirical work.
      METHODS: We identified three key disclosure behaviours: finding out what the
      patient already knows or suspects about their diagnosis; using the actual words
      'dementia' or 'Alzheimer's disease' when talking to the patient; and exploring
      what the diagnosis means to the patient. We conducted a questionnaire survey of
      older peoples' mental health teams (MHTs) based upon theoretical constructs from
      the Theory of Planned Behaviour (TPB) and Social Cognitive Theory (SCT) and used
      the findings to identify factors that predicted mental health professionals'
      intentions to perform each behaviour. We selected behaviour change techniques
      likely to alter these factors. RESULTS: The change techniques selected were:
      persuasive communication to target subjective norm; behavioural modelling and
      graded tasks to target self-efficacy; persuasive communication to target attitude
      towards the use of explicit terminology when talking to the patient; and
      behavioural modelling by MHTs to target perceived behavioural control for finding
      out what the patient already knows or suspects and exploring what the diagnosis
      means to the patient. We operationalised these behaviour change techniques using
      an interactive 'pen and paper' intervention designed to increase intentions to
      perform the three target behaviours. CONCLUSION: It is feasible to develop an
      intervention to change professional behaviour based upon theoretical models,
      empirical data and evidence based behaviour change techniques. The next step is
      to evaluate the effect of such an intervention on behavioural intention. We argue
      that this approach to development and reporting of interventions will contribute
      to the science of implementation by providing replicable interventions that
      illuminate the principles and processes underlying change.

PMID- 18093313
TI  - Adjuvant whole abdominal intensity modulated radiotherapy (IMRT) for high risk
      stage FIGO III patients with ovarian cancer (OVAR-IMRT-01) - Pilot trial of a
      phase I/II study: study protocol.
AB  - BACKGROUND: The prognosis for patients with advanced epithelial ovarian cancer
      remains poor despite aggressive surgical resection and platinum-based
      chemotherapy. More than 60% of patients will develop recurrent disease,
      principally intraperitoneal, and die within 5 years. The use of whole abdominal
      irradiation (WAI) as consolidation therapy would appear to be a logical strategy
      given its ability to sterilize small tumour volumes. Despite the clinically
      proven efficacy of whole abdominal irradiation, the use of radiotherapy in
      ovarian cancer has profoundly decreased mainly due to high treatment-related
      toxicity. Modern intensity-modulated radiation therapy (IMRT) could allow to
      spare kidneys, liver, and bone marrow while still adequately covering the
      peritoneal cavity with a homogenous dose. METHODS/DESIGN: The OVAR-IMRT-01 study
      is a single center pilot trial of a phase I/II study. Patients with advanced
      ovarian cancer stage FIGO III (R1 or R2< 1 cm) after surgical resection and
      platinum-based chemotherapy will be treated with whole abdomen irradiation as
      consolidation therapy using intensity modulated radiation therapy (IMRT) to a
      total dose of 30 Gy in 1.5 Gy fractions. A total of 8 patients will be included
      in this trial. For treatment planning bone marrow, kidneys, liver, spinal cord,
      vertebral bodies and pelvic bones are defined as organs at risk. The planning
      target volume includes the entire peritoneal cavity plus pelvic and para-aortic
      node regions. DISCUSSION: The primary endpoint of the study is the evaluation of
      the feasibility of intensity-modulated WAI and the evaluation of the study
      protocol. Secondary endpoint is evaluation of the toxicity of intensity modulated
      WAI before continuing with the phase I/II study. The aim is to explore the
      potential of IMRT as a new method for WAI to decrease the dose to kidneys, liver,
      bone marrow while covering the peritoneal cavity with a homogenous dose, and to
      implement whole abdominal intensity-modulated radiotherapy into the adjuvant
      multimodal treatment concept of advanced ovarian cancer FIGO stage III.

PMID- 18093314
TI  - Downregulation of COP9 signalosome subunits differentially affects the CSN
      complex and target protein stability.
AB  - BACKGROUND: The COP9 signalosome (CSN) is a conserved protein complex in
      eukaryotic cells consisting of eight subunits (CSN1 to CSN8). Recent data
      demonstrate that the CSN is a regulator of the ubiquitin (Ub) proteasome system
      (UPS). It controls substrate ubiquitination by cullin-RING Ub ligases (CRLs), a
      process that determines substrate specificity of the UPS. The intrinsic
      deneddylating activity localized to CSN5 as well as the associated kinases and
      deubiquitinating activity are involved in the regulatory function of CSN. The
      exact mechanisms are unclear. In this study we knocked down CSN1 (siCSN1), CSN3
      (siCSN3) and CSN5 (siCSN5) by specific siRNA oligos permanently expressed in HeLa
      cells. The analysis and comparison of siRNA cells revealed differential impact of
      individual subunits on CSN structure and function. RESULTS: Permanent knockdowns
      of CSN1 and CSN3 led to a reduction of the subunits to approximately 40%, which
      is accompanied by a proportional decrease of the CSN holocomplex. In contrast,
      downregulation of CSN5 in HeLa cells reduced the CSN5 protein below 20% without
      significant effects on the remaining complex. The CRL component Rbx1 was
      characterized by accelerated proteolysis in siCSN1 and siCSN3 and also in siCSN5
      cells, however, with lesser extent. Immunoprecipitated CSN complex from siCSN5
      cells was less effective in phosphorylating c-Jun and p27. Accelerated
      degradation of c-Jun in siCSN5 cells was rescued by overexpression of CSN5 as
      well as of the deneddylation mutant CSN5D151N. Overexpression of CSN5 cannot
      rescue c-Jun destabilization in siCSN1. CONCLUSION: There exists a coordinated
      downregulation of CSN subunits in the CSN1 and CSN3 knockdowns. The underlying
      regulatory mechanisms are obscure. CSN5 seems to possess a specific status in
      HeLa cells. Its reduction is not connected with coordinated downregulation of
      other subunits. CSN knockdowns confirm that the stabilization of the CRL
      component Rbx1 is a major CSN function. In addition, downregulation of CSN
      subunits influences the stability of important cellular regulators such as c-Jun
      and p27.

PMID- 18093315
TI  - Identification of a novel conserved mixed-isoform B56 regulatory subunit and
      spatiotemporal regulation of protein phosphatase 2A during Xenopus laevis
      development.
AB  - BACKGROUND: Wnt signaling is a key regulator of development and tumorigenesis.
      Protein phosphatase 2A (PP2A), which consists of a catalytic C, a structural A,
      and a regulatory B subunit, plays diverse roles in Wnt signaling through its B56
      subunits. B56 is a multigene family encoding for proteins with a conserved core
      domain and divergent amino- and carboxy-termini. Ectopic B56alpha and B56gamma
      reduce beta-catenin abundance and B56alpha reduces Wnt-dependent transcription,
      suggesting that B56alpha and B56gamma inhibit Wnt signaling. In contrast,
      B56epsilon is required for Wnt signaling. Knowledge of where and when B56
      subunits are expressed during Xenopus development will aid in our understanding
      of their roles in Wnt signaling. RESULTS: We have undertaken expression analyses
      of B56alpha and B56gamma in Xenopus laevis. We cloned Xenopus B56alpha; it is 88%
      identical to human B56alpha. Xenopus B56gamma is 94% identical with human
      B56gamma, however, a novel evolutionarily conserved mixed-isoform transcript was
      identified that contains a B56delta-like amino-terminal domain and a B56gamma
      core domain. The B56delta-like variable domain exon is located upstream of the
      B56gamma variable domain exon at the human B56gamma locus, suggesting that the
      mixed-isoform transcript is due to alternative splicing. B56gamma transcripts
      with different 3' ends were identified that lack or possess a 35 base pair
      sequence, resulting in either a transcript similar to human B56gamma1, or an
      uncharacterized evolutionarily conserved sequence. Real time RT-PCR analyses
      revealed that B56alpha is expressed at moderate levels before the midblastula
      transition (MBT), at reduced levels during gastrulation and neurulation, and at
      high levels during organogenesis, while B56gamma is expressed at low levels until
      organogenesis. B56alpha is enriched in the ventral hemisphere pre-MBT, while
      B56gamma is ventrally enriched post-MBT. Aalpha, Abeta, Calpha and Cbeta are
      expressed in early Xenopus development, suggesting the presence of a functional
      heterotrimer. CONCLUSION: Our data suggest that B56 functional diversity is
      achieved in part through the synthesis of a novel mixed-isoform B56delta/gamma
      transcript. Our data also suggest that B56alpha functions pre-MBT, inhibiting Wnt
      signaling on the ventral side of the embryo, and again during organogenesis,
      while B56gamma functions primarily post-MBT.

PMID- 18093316
TI  - Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas
      and adenomas.
AB  - BACKGROUND: The risk of sporadic colorectal cancer (CRC) is mainly associated
      with lifestyle factors, particularly dietary factors. Diets high in red meat and
      fat and low in fruit and vegetables are associated with an increased risk of CRC.
      The dietary effects may be modulated by genetic polymorphisms in
      biotransformation genes. In this study we aimed to evaluate the role of dietary
      factors in combination with genetic factors in the different stages of colorectal
      carcinogenesis in a Norwegian population. METHODS: We used a case-control study
      design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400
      controls) to test the association between dietary factors (meat versus fruit,
      berries and vegetables) genetic polymorphisms in biotransformation genes (GSTM1,
      GSTT1, GSTP1 Ile105Val, EPHX1 Tyr113His and EPHX1 His139Arg), and risk of
      colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval
      (95% CI) were estimated by binary logistic regression. RESULTS: A higher ratio of
      total meat to total fruit, berry and vegetable intake was positively associated
      with both high and low-risk adenomas, with approximately twice the higher risk in
      the 2nd quartile compared to the lowest quartile. For the high-risk adenomas this
      positive association was more obvious for the common allele (Tyr allele) of the
      EPHX1 codon 113 polymorphism. An association was also observed for the EPHX1
      codon 113 polymorphism in the low-risk adenomas, although not as obvious.
      CONCLUSION: Although, the majority of the comparison groups are not significant,
      our results suggest an increased risk of colorectal adenomas in individuals for
      some of the higher ratios of total meat to total fruit, berry and vegetable
      intake. In addition the study supports the notion that the biotransformation
      enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the
      risk of developing colorectal carcinoma and adenoma.

PMID- 18093318
TI  - Human resources requirements for highly active antiretroviral therapy scale-up in
      Malawi.
AB  - BACKGROUND: Twelve percent of the adult population in Malawi is estimated to be
      HIV infected. About 15% to 20% of these are in need of life saving antiretroviral
      therapy. The country has a public sector-led antiretroviral treatment program
      both in the private and public health sectors. Estimation of the clinical human
      resources needs is required to inform the planning and distribution of health
      professionals. METHODS: We obtained data on the total number of patients on
      highly active antiretroviral treatment program from the Malawi National AIDS
      Commission and Ministry of Health, HIV Unit, and the number of registered health
      professionals from the relevant regulatory bodies. We also estimated number of
      health professionals required to deliver highly active antiretroviral therapy
      (HAART) using estimates of human resources from the literature. We also obtained
      data from the Ministry of Health on the actual number of nurses, clinical
      officers and medical doctors providing services in HAART clinics. We then made
      comparisons between the human resources situation on the ground and the
      theoretical estimates based on explicit assumptions. RESULTS: There were 610
      clinicians (396 clinical officers and 214 physicians), 44 pharmacists and 98
      pharmacy technicians and 7264 nurses registered in Malawi. At the end of March
      2007 there were 85 clinical officer and physician full-time equivalents (FTEs)
      and 91 nurse FTEs providing HAART to 95,674 patients. The human resources used
      for the delivery of HAART comprised 13.9% of all clinical officers and physicians
      and 1.1% of all nurses. Using the estimated numbers of health professionals from
      the literature required 15.7-31.4% of all physicians and clinical officers, 66.5
      199.3% of all pharmacists and pharmacy technicians and 2.6 to 9.2% of all the
      available nurses. To provide HAART to all the 170,000 HIV infected persons
      estimated as clinically eligible would require 4.7% to 16.4% of the total number
      of nurses, 118.1% to 354.2% of all the available pharmacists and pharmacy
      technicians and 27.9% to 55.7% of all clinical officers and physicians. The
      actual number of health professionals working in the delivery of HAART in the
      clinics represented 44% to 88.8% (for clinical officers and medical doctors) and
      13.6% and 47.6% (for nurses), of what would have been needed based on the
      literature estimation. CONCLUSION: HAART provision is a labour intensive
      exercise. Although these data are insufficient to determine whether HAART scale
      up has resulted in the weakening or strengthening of the health systems in
      Malawi, the human resources requirements for HAART scale-up are significant.
      Malawi is using far less human resources than would be estimated based on the
      literature from other settings. The impact of HAART scale-up on the overall
      delivery of health services should be assessed.

PMID- 18093317
TI  - Identification of two novel activities of the Wnt signaling regulator Dickkopf 3
      and characterization of its expression in the mouse retina.
AB  - BACKGROUND: The Wnt signaling pathway is a cellular communication pathway that
      plays critical roles in development and disease. A major class of Wnt signaling
      regulators is the Dickkopf (Dkk) family of secreted glycoproteins. Although the
      biological properties of Dickkopf 1 (Dkk1) and Dickkopf 2 (Dkk2) are well
      characterized, little is known about the function of the related Dickkopf 3
      (Dkk3) protein in vivo or in cell lines. We recently demonstrated that Dkk3
      transcripts are upregulated during photoreceptor death in a mouse model of
      retinal degeneration. In this study, we characterized the activity of Dkk3 in Wnt
      signaling and cell death. RESULTS: Dkk3 was localized to Muller glia and retinal
      ganglion cells in developing and adult mouse retina. Western blotting confirmed
      that Dkk3 is secreted from Muller glia cells in culture. We demonstrated that
      Dkk3 potentiated Wnt signaling in Muller glia and HEK293 cells but not in COS7
      cells, indicating that it is a cell-type specific regulator of Wnt signaling.
      This unique Dkk3 activity was blocked by co-expression of Dkk1. Additionally,
      Dkk3 displayed pro-survival properties by decreasing caspase activation and
      increasing viability in HEK293 cells exposed to staurosporine and H2O2. In
      contrast, Dkk3 did not protect COS7 cells from apoptosis. CONCLUSION: These data
      demonstrate that Dkk3 is a positive regulator of Wnt signaling, in contrast to
      its family member Dkk1. Furthermore, Dkk3 protects against apoptosis by reducing
      caspase activity, suggesting that Dkk3 may play a cytoprotective role in the
      retina.

PMID- 18093319
TI  - Estimated financial and human resources requirements for the treatment of malaria
      in Malawi.
AB  - BACKGROUND: Malaria fever is a common medical presentation and diagnosis in
      Malawi. The national malaria policy supports self-diagnosis and self-medication
      for uncomplicated malaria with first line anti-malaria drugs. While a qualitative
      appreciation of the burden of malaria on the health system is recognized, there
      is limited quantitative estimation of the burden malaria exacts on the health
      system, especially with regard to human resources and financial burden on Malawi.
      METHODS: The burden of malaria was assessed based on estimated incidence rates
      for a high endemic country of which Malawi is one. Data on the available human
      resources and financial resources committed towards malaria from official Malawi
      government documents and programme reports were obtained. The amount of human and
      financial resources that would be required to treat 65% or 85% of symptomatic
      malaria cases as per the Roll Back Malaria partnership and the US President's
      Malaria Initiative targets. RESULTS: Based on a malaria incidence rate of 1.4
      episodes per year per person it was estimated that there would be 3.71 million
      symptomatic episodes of malaria among children <5 years of age based on mid-2007
      census projections. At 0.59 episodes each year per person there would be 2.13
      million episodes in the 5 to 14 year age group and 1.02 million episodes in.
      There would be 761,848 malaria cases when HIV is not factored in among those 15
      years of age or above; this figure rose to 2.2 million when the impact of HIV in
      increasing malaria incidence was considered. The prevalence of HIV has resulted
      in 42.3% increase in symptomatic malaria cases. Treating 65% to 85% of cases
      would result in using 8.9% to 12.2% of the national health budget or 22.2% to
      33.2% of the national drug budget. Furthermore, having 65% to 85% of cases
      treated at a health facility would consume 55.5% to 61.1% of full-time
      equivalents of all the clinicians registered in the country. While this study's
      estimated time of 5 and 10 minutes per consultation may differ in actual
      practice, due to time constraints patients may not be seen for longer
      consultation in resources limited settings. CONCLUSION: Malaria exacts a heavy
      toll on the health system in Malawi. The national recommendation of self
      medication with first-line drug for uncomplicated malaria is justified as there
      are not enough clinicians to provide clinical care for all cases. The Malawi
      Ministry of Health's promotion of malaria drug prescription including other lower
      cadre health workers may be justified.

PMID- 18093321
TI  - An HIV/AIDS Prophylactic vaccine is possible.
AB  - One needs to think outside of the box, as one of us (Ronald B Luftig) learned
      from many years as a mathematician, and a biophysicist.In this short Review, the
      need to focus on producing high levels of neutralizing antibodies (NAbs) to
      incoming and conformationally altered virus after it has bound to CD4+ cells is
      essential.Increasing the number of gp120 molecules on the surface of L-2
      particles, could allow for an enhanced number of NAbs.The attempt at increasing
      CD8+ T cell responses in recent vaccine trials has not worked perhaps because it
      may have allowed HIV to enter into remote sanctuaries. Our approach focuses on
      increasing NAbs, before high levels of CD8+ T cells are produced.

PMID- 18093322
TI  - An estimate of carbon emissions from 2004 wildfires across Alaskan Yukon River
      Basin.
AB  - BACKGROUND: Wildfires are an increasingly important component of the forces that
      drive the global carbon (C) cycle and climate change as progressive warming is
      expected in boreal areas. This study estimated C emissions from the wildfires
      across the Alaskan Yukon River Basin in 2004. We spatially related the firescars
      to land cover types and defined the C fractions of aboveground biomass and the
      ground layer (referring to the top 15 cm organic soil layer only in this paper)
      consumed in association with land cover types, soil drainage classes, and the C
      stocks in the ground layer. RESULTS: The fires led to a burned area of 26,500 km2
      and resulted in the total C emission of 81.1 +/- 13.6 Tg (Tg, Teragram; 1 Tg =
      1012 g) or 3.1 +/- 0.7 kg C m-2 burned. Of the total C emission, about 73% and
      27% could be attributed to the consumption of the ground layer and aboveground
      biomass, respectively. CONCLUSION: The predominant contribution of the ground
      layer to the total C emission implies the importance of ground fuel management to
      the control of wildfires and mitigation of C emissions. The magnitude of the
      total C emission depends on fire extent, while the C loss in kg C m-2 burned is
      affected strongly by the ground layer and soil drainage condition. The
      significant reduction in the ground layer by large fires may result in profound
      impacts on boreal ecosystem services with an increase in feedbacks between
      wildfires and climate change.

PMID- 18093320
TI  - Identification of chromosomal alpha-proteobacterial small RNAs by comparative
      genome analysis and detection in Sinorhizobium meliloti strain 1021.
AB  - BACKGROUND: Small untranslated RNAs (sRNAs) seem to be far more abundant than
      previously believed. The number of sRNAs confirmed in E. coli through various
      approaches is above 70, with several hundred more sRNA candidate genes under
      biological validation. Although the total number of sRNAs in any one species is
      still unclear, their importance in cellular processes has been established.
      However, unlike protein genes, no simple feature enables the prediction of the
      location of the corresponding sequences in genomes. Several approaches, of
      variable usefulness, to identify genomic sequences encoding sRNA have been
      described in recent years. RESULTS: We used a combination of in silico
      comparative genomics and microarray-based transcriptional profiling. This
      approach to screening identified ~60 intergenic regions conserved between
      Sinorhizobium meliloti and related members of the alpha-proteobacteria sub-group
      2. Of these, 14 appear to correspond to novel non-coding sRNAs and three are
      putative peptide-coding or 5' UTR RNAs (ORF smaller than 100 aa). The expression
      of each of these new small RNA genes was confirmed by Northern blot
      hybridization. CONCLUSION: Small non coding RNA (sra) genes can be found in the
      intergenic regions of alpha-proteobacteria genomes. Some of these sra genes are
      only present in S. meliloti, sometimes in genomic islands; homologues of others
      are present in related genomes including those of the pathogens Brucella and
      Agrobacterium.

PMID- 18093323
TI  - The role of neighborhood level socioeconomic characteristics in Salmonella
      infections in Michigan (1997-2007): assessment using geographic information
      system.
AB  - BACKGROUND: The majority of U.S. disease surveillance systems contain incomplete
      information regarding socioeconomic status (SES) indicators like household or
      family income and educational attainment in case reports, which reduces the
      usefulness of surveillance data for these parameters. We investigated the
      association between select SES attributes at the neighborhood level and
      Salmonella infections in the three most populated counties in Michigan using a
      geographic information system. METHODS: We obtained data on income, education,
      and race from the 2000 U.S. Census, and the aggregate number of laboratory
      confirmed cases of salmonellosis (1997-2006) at the block group level from the
      Michigan Department of Community Health. We used ArcGIS to visualize the
      distribution, and Poisson regression analysis to study associations between
      potential predictor variables and Salmonella infections. RESULTS: Based on data
      from 3,419 block groups, our final multivariate model revealed that block groups
      with lower educational attainment were less commonly represented among cases than
      their counterparts with higher education levels (< high school degree vs. > or =
      college degree: rate ratio (RR) = 0.79, 95% confidence interval (CI):0.63, 0.99;
      > or = and high school degree, but no college degree vs. > or = college degree:
      RR = 0.84, 95% CI: 0.76, 0.92). Levels of education also showed a dose-response
      relation with the outcome variable, i.e., decreasing years of education was
      associated with a decrease in Salmonella infections incidence at the block group
      level. CONCLUSION: Education plays a significant role in health-seeking behavior
      at the population level. It is conceivable that a reporting bias may exist due to
      a greater detection of Salmonella infections among high education block groups
      compared to low education block groups resulting from differential access to
      healthcare. In addition, individuals of higher education block groups who also
      have greater discretionary income may eat outside the home frequently and be more
      likely to own pets considered reservoirs of Salmonella, which increase the
      likelihood of contracting Salmonella infections compared to their counterparts
      with lower levels of education. Public health authorities should focus on
      improving the level of disease detection and reporting among communities with
      lower income and education and further evaluate the role of higher educational
      attainment in the predisposition for salmonellosis.

PMID- 18093324
TI  - Carbachol-mediated pigment granule dispersion in retinal pigment epithelium
      requires Ca2+ and calcineurin.
AB  - BACKGROUND: Inside bluegill (Lepomis macrochirus) retinal pigment epithelial
      cells, pigment granules move in response to extracellular signals. During the
      process of aggregation, pigment motility is directed toward the cell nucleus; in
      dispersion, pigment is directed away from the nucleus and into long apical
      processes. A number of different chemicals have been found to initiate
      dispersion, and carbachol (an acetylcholine analog) is one example. Previous
      research indicates that the carbachol-receptor interaction activates a Gq
      mediated pathway which is commonly linked to Ca2+ mobilization. The purpose of
      the present study was to test for involvement of calcium and to probe calcium
      dependent mediators to reveal their role in carbachol-mediated dispersion.
      RESULTS: Carbachol-induced pigment granule dispersion was blocked by the calcium
      chelator BAPTA. In contrast, the calcium channel antagonist verapamil, and
      incubation in Ca2+-free medium failed to block carbachol-induced dispersion. The
      calcineurin inhibitor cypermethrin blocked carbachol-induced dispersion; whereas,
      two protein kinase C inhibitors (staurosporine and bisindolylmaleimide II) failed
      to block carbachol-induced dispersion, and the protein kinase C activator phorbol
      12-myristate 13-acetate failed to elicit dispersion. CONCLUSION: A rise in
      intracellular calcium is necessary for carbachol-induced dispersion; however, the
      Ca2+ requirement is not dependent on extracellular sources, implying that
      intracellular stores are sufficient to enable pigment granule dispersion to
      occur. Calcineurin is a likely Ca2+-dependent mediator involved in the signal
      cascade. Although the pathway leads to the generation of diacylglycerol and
      calcium (both required for the activation of certain PKC isoforms), our evidence
      does not support a significant role for PKC.

PMID- 18093325
TI  - Structural analysis of inhibition of E. coli methionine aminopeptidase:
      implication of loop adaptability in selective inhibition of bacterial enzymes.
AB  - BACKGROUND: Methionine aminopeptidase is a potential target of future
      antibacterial and anticancer drugs. Structural analysis of complexes of the
      enzyme with its inhibitors provides valuable information for structure-based drug
      design efforts. RESULTS: Five new X-ray structures of such enzyme-inhibitor
      complexes were obtained. Analysis of these and other three similar structures
      reveals the adaptability of a surface-exposed loop bearing Y62, H63, G64 and Y65
      (the YHGY loop) that is an integral part of the substrate and inhibitor binding
      pocket. This adaptability is important for accommodating inhibitors with
      variations in size. When compared with the human isozymes, this loop either
      becomes buried in the human type I enzyme due to an N-terminal extension that
      covers its position or is replaced by a unique insert in the human type II
      enzyme. CONCLUSION: The adaptability of the YHGY loop in E. coli methionine
      aminopeptidase, and likely in other bacterial methionine aminopeptidases, enables
      the enzyme active pocket to accommodate inhibitors of differing size. The
      differences in this adaptable loop between the bacterial and human methionine
      aminopeptidases is a structural feature that can be exploited to design
      inhibitors of bacterial methionine aminopeptidases as therapeutic agents with
      minimal inhibition of the corresponding human enzymes.

PMID- 18093326
TI  - Monomorphic post-transplant lymphoproliferative disorder of the tongue: case
      report and review of literature.
AB  - BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of
      hematological diseases arising in context of immunosuppression after organ
      transplantation. PTLD can involve any organ; however, it is extremely rare in
      oral cavity. METHODS: Using morphologic and immunophenotypic approaches we have
      studied a case of monomorphic PTLD of the tongue that developed in a patient
      following unilateral kidney and pancreas transplantation on immunosuppressive
      therapy. Additionally, cases of PTLD in the oral cavity were reviewed in the
      English literature. RESULTS: The neoplasm showed large cell morphology and B-cell
      phenotype. In situ hybridization for Epstein-Barr virus was positive. Complete
      remission was obtained after decreasing immunosuppressive therapy. The patient
      remained in remission at 790 days' follow up. CONCLUSION: This rare case
      increased our awareness of PTLD in the oral cavity of patients following solid
      organ transplantation and immunosuppressive therapy.

PMID- 18093327
TI  - Characteristics associated with US Walk to School programs.
AB  - Participation in Walk to School (WTS) programs has grown substantially in the US
      since its inception; however, no attempt has been made to systematically describe
      program use or factors associated with implementation of environment/policy
      changes. OBJECTIVE: Describe the characteristics of schools' WTS programs by
      level of implementation. METHODS: Representatives from 450 schools from 42 states
      completed a survey about their WTS program's infrastructure and activities, and
      perceived impact on walking to school. Level of implementation was determined
      from a single question to which respondents reported participation in WTS Day
      only (low), WTS Day and additional programs (medium), or making
      policy/environmental change (high). RESULTS: The final model showed number of
      community groups involved was positively associated with higher level of
      implementation (OR = 1.78, 95%CI = 1.44, 2.18), as was funding (OR = 1.56, 95%CI
      = 1.26, 1.92), years of participation (OR = 1.44, 95% CI = 1.23, 1.70), and use
      of a walkability assessment (OR = 3.22, 95%CI = 1.84, 5.64). Implementation level
      was modestly associated with increased walking (r = 0.18). CONCLUSION: Strong
      community involvement, some funding, repeat participation, and environmental
      audits are associated with progms that adopt environmental/policy change, and
      seem to facilitate walking to school.

PMID- 18093328
TI  - PARPs database: a LIMS systems for protein-protein interaction data mining or
      laboratory information management system.
AB  - BACKGROUND: In the "post-genome" era, mass spectrometry (MS) has become an
      important method for the analysis of proteins and the rapid advancement of this
      technique, in combination with other proteomics methods, results in an increasing
      amount of proteome data. This data must be archived and analysed using
      specialized bioinformatics tools. DESCRIPTION: We herein describe "PARPs
      database," a data analysis and management pipeline for liquid chromatography
      tandem mass spectrometry (LC-MS/MS) proteomics. PARPs database is a web-based
      tool whose features include experiment annotation, protein database searching,
      protein sequence management, as well as data-mining of the peptides and proteins
      identified. CONCLUSION: Using this pipeline, we have successfully identified
      several interactions of biological significance between PARP-1 and other
      proteins, namely RFC-1, 2, 3, 4 and 5.

PMID- 18093329
TI  - Mucocele of the appendix - a diagnostic dilemma: a case report.
AB  - INTRODUCTION: Mucocele of the appendix secondary to mucinous cystadenoma is a
      rare clinical finding. Clinical presentation is varied with more than half being
      asymptomatic. CASE PRESENTATION: We report such a case presenting to the surgeons
      where initial clinical findings and investigations suggested an ovarian cyst. The
      patient was subsequently referred to the Gynaecologists for further management.
      In spite of extensive preoperative investigations, the diagnosis was only made at
      the time of surgery. CONCLUSION: In women presenting with a right iliac fossa
      mass and clinical features not indicative of gynaecological pathology, an
      appendiceal origin should be considered in the differential diagnosis.

PMID- 18093331
TI  - Internet-based treatment for adults with depressive symptoms: the protocol of a
      randomized controlled trial.
AB  - BACKGROUND: Depression is a highly prevalent condition, affecting more than 15%
      of the adult population at least once in their lives. Guided self-help is
      effective in the treatment of depression. The purpose of this study is to
      investigate the effectiveness of two Internet-based guided self-help treatments
      with adults reporting elevated depressive symptoms. Other research questions
      concern the identification of potential mediators and the search for subgroups
      who respond differently to the interventions. METHODS: This study is a randomized
      controlled trial with three conditions: two treatment conditions and one waiting
      list control group. The two treatment conditions are Internet-based cognitive
      behavior therapy and Internet-based problem-solving therapy. They consist of 8
      and 5 weekly lessons respectively. Both interventions are combined with support
      by e-mail. Participants in the waiting list control group receive the
      intervention three months later. The study population consists of adults from the
      general population. They are recruited through advertisements in local and
      national newspapers and through banners on the Internet. Subjects with symptoms
      of depression (> or = 16 on the Center for Epidemiological Studies Depression
      scale) are included. Other inclusion criteria are having sufficient knowledge of
      the Dutch language, access to the Internet and an e-mail address. Primary outcome
      is depressive symptoms. Secondary outcomes are anxiety, quality of life,
      dysfunctional cognitions, worrying, problem solving skills, mastery, absence at
      work and use of healthcare. We will examine the following variables as potential
      mediators: dysfunctional cognitions, problem solving skills, worrying, anxiety
      and mastery. Potential moderating variables are: socio-demographic
      characteristics and symptom severity. Data are collected at baseline and at 5
      weeks, 8 weeks, 12 weeks and 9 months after baseline. Analyses will be conducted
      on the intention-to-treat sample. DISCUSSION: This study evaluates two Internet
      based treatments for depression, namely cognitive behavioral therapy and problem
      solving therapy. The effectiveness of Internet-based problem-solving therapy
      suggest that this may be a worthwhile alternative to other more intensive
      treatment options. Strengths and limitations of this study are discussed. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN16823487.

PMID- 18093332
TI  - A phase III trial comparing an anionic phospholipid-based cream and aloe vera
      based gel in the prevention of radiation dermatitis in pediatric patients.
AB  - PURPOSE: Radiation dermatitis is a common side effect of radiation therapy (RT).
      In severe cases, RT must be interrupted until the skin heals, which can
      compromise treatment. The purpose of the study was to compare an anionic polar
      phospholipid (APP)-based cream and an aloe vera-based gel to determine their
      effectiveness in preventing and treating radiation dermatitis. PATIENTS AND
      METHODS: Forty-five pediatric patients (median age, 11 years) with various
      diagnoses who received at least 23.4 Gy participated. APP cream and aloe vera gel
      were symmetrically applied within the irradiated field after each treatment.
      Three measures were collected before, during and after completion of treatment:
      subject's skin comfort, dermatologic assessment, and common toxicity criteria
      (CTC). RESULTS: Significant differences in specific variables favoring APP cream
      use were noted in some patients including skin comfort variables, dry (p =
      0.002), soft (p = 0.057), feels good (p = 0.002), rough (p = 0.065), smooth (p =
      0.012) and dermatologic variables, dryness (p = 0.013), erythema (p = 0.002) and
      peely (p = 0.008). Grouped CTC scores were supportive of APP cream (p = 0.004).
      In comparing the first and last assessments, two dermatologic variables, dryness
      (p = 0.035) and peely (p = 0.016), favored APP cream. CONCLUSION: APP cream is
      more effective than aloe vera-based gel for prevention and treatment of radiation
      dermatitis.

PMID- 18093330
TI  - Checkpoint independence of most DNA replication origins in fission yeast.
AB  - BACKGROUND: In budding yeast, the replication checkpoint slows progress through S
      phase by inhibiting replication origin firing. In mammals, the replication
      checkpoint inhibits both origin firing and replication fork movement. To find out
      which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we
      used microarrays to investigate the use of origins by wild-type and checkpoint
      mutant strains in the presence of hydroxyurea (HU), which limits the pool of
      deoxyribonucleoside triphosphates (dNTPs) and activates the replication
      checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which
      encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission
      yeast homologue of Chk2). RESULTS: Our microarray results proved to be largely
      consistent with those independently obtained and recently published by three
      other laboratories. However, we were able to reconcile differences between the
      previous studies regarding the extent to which fission yeast replication origins
      are affected by the replication checkpoint. We found (consistent with the three
      previous studies after appropriate interpretation) that, in surprising contrast
      to budding yeast, most fission yeast origins, including both early- and late
      firing origins, are not significantly affected by checkpoint mutations during
      replication in the presence of HU. A few origins (approximately 3%) behaved like
      those in budding yeast: they replicated earlier in the checkpoint mutants than in
      wild type. These were located primarily in the heterochromatic subtelomeric
      regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the
      strongest checkpoint restraint correspond precisely to previously mapped
      subtelomeric heterochromatin. This observation implies that subtelomeric
      heterochromatin in fission yeast differs from heterochromatin at centromeres, in
      the mating type region, and in ribosomal DNA, since these regions replicated at
      least as efficiently in wild-type cells as in checkpoint-mutant cells.
      CONCLUSION: The fact that approximately 97% of fission yeast replication origins 
      both early and late - are not significantly affected by replication checkpoint
      mutations in HU-treated cells suggests that (i) most late-firing origins are
      restrained from firing in HU-treated cells by at least one checkpoint-independent
      mechanism, and (ii) checkpoint-dependent slowing of S phase in fission yeast when
      DNA is damaged may be accomplished primarily by the slowing of replication forks.

PMID- 18093333
TI  - Specific elements of the glyoxylate pathway play a significant role in the
      functional transition of the soybean cotyledon during seedling development.
AB  - BACKGROUND: The soybean (Glycine max) cotyledon is a specialized tissue whose
      main function is to serve as a nutrient reserve that supplies the needs of the
      young plant throughout seedling development. During this process the cotyledons
      experience a functional transition to a mainly photosynthetic tissue. To identify
      at the genetic level the specific active elements that participate in the natural
      transition of the cotyledon from storage to photosynthetic activity, we studied
      the transcript abundance profile at different time points using a new soybean
      oligonucleotide chip containing 19,200 probes (70-mer long). RESULTS: After
      normalization and statistical analysis we determined that 3,594 genes presented a
      statistically significant altered expression in relation to the imbibed seed in
      at least one of the time points defined for the study. Detailed analysis of this
      data identified individual, specific elements of the glyoxylate pathway that play
      a fundamental role during the functional transition of the cotyledon from
      nutrient storage to photosynthesis. The dynamics between glyoxysomes and
      peroxisomes is evident during these series of events. We also identified several
      other genes whose products could participate co-ordinately throughout the
      functional transition and the associated mechanisms of control and regulation and
      we described multiple unknown genetic elements that by association have the
      potential to make a major contribution to this biological process. CONCLUSION: We
      demonstrate that the global transcript profile of the soybean cotyledon during
      seedling development is extremely active, highly regulated and dynamic. We
      defined the expression profiles of individual gene family members, enzymatic
      isoforms and protein subunits and classified them accordingly to their
      involvement in different functional activities relevant to seedling development
      and the cotyledonary functional transition in soybean, especially the ones
      associated with the glyoxylate cycle. Our data suggests that in the soybean
      cotyledon a very complex and synchronized system of control and regulation of
      several metabolic pathways is essential to carry out the necessary functions
      during this developmental process.

PMID- 18093334
TI  - The enhanced expression of the matrix metalloproteinase 9 in nasal NK/T-cell
      lymphoma.
AB  - BACKGROUND: Nasal NK/T cell lymphoma is an aggressive disease and has a poor
      prognosis. Nasal NK/T cell lymphoma is refractory to conventional chemotherapy
      and has strong tendency of widespread relapse or dissemination into distant
      sites. METHODS: We immunohistochemically studied nasal NK/T-cell lymphoma to
      elucidate the unique characteristics of nasal NK/T-cell lymphoma, such as its
      higher metastatic tendency and its vast necrosis which leads to destruction of
      the involved tissues. The expression of P-glycoprotein and MMP-9 was evaluated in
      the 20 patients with nasal NK/T-cell lymphoma and 25 with nasal non-NK/T-cell
      lymphoma and the relationship between expression of these proteins and clinical
      results were analyzed in this report. RESULTS: Overall 5-year survival rates for
      patients with nasal NK/T cell lymphoma, and nasal non-NK/T cell lymphoma were
      51%, and 84%. Distant involvement free 5-year survival rates for patients with
      nasal NK/T cell lymphoma, and nasal non-NK/T cell lymphoma were 53%, and 79%.
      Overall positivity for P-glycoprotein was observed in 10 of 19 patients with NTL
      and in 13 of 23 patients with non-NTL. When the overall survival rate was
      compared between patients with P-glycoprotein positive and negative, there was no
      difference between them. Sixteen of the 19 patients with nasal NK/T cell lymphoma
      expressed MMP-9. In contrast, only 8 of the 22 patients with nasal non-NK/T cell
      lymphoma expressed MMP-9. Distant involvement free 5-year survival rates for
      patients with MMP-9 negative, and MMP-9 positive were 92%, and 61%, respectively.
      The difference was statistically significant (p = 0.027). CONCLUSION: Positive
      immunoreactivity for P-glycoprotein was not an independent prognostic factor in
      nasal NK/T-cell lymphomas, which stresses the importance of exploring other
      mechanisms of drug resistance. The strong expression of MMP-9 is uniquely
      characteristic of nasal NK/T cell lymphoma and may contribute to its strong
      tendency to disseminatate and the extensive necrosis which is always seen.
      However, our results are based on univariate comparisons, and as such, should be
      viewed with some caution.

PMID- 18093335
TI  - Autologous glioma cell vaccine admixed with interleukin-4 gene transfected
      fibroblasts in the treatment of patients with malignant gliomas.
AB  - BACKGROUND: The prognosis for malignant gliomas remains dismal. We addressed the
      safety, feasibility and preliminary clinical activity of the vaccinations using
      autologous glioma cells and interleukin (IL)-4 gene transfected fibroblasts.
      METHODS: In University of Pittsburgh Cancer Institute (UPCI) protocol 95-033,
      adult participants with recurrent glioblastoma multiforme (GBM) or anaplastic
      astrocytoma (AA) received gross total resection (GTR) of the recurrent tumors,
      followed by two vaccinations with autologous fibroblasts retrovirally transfected
      with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In
      UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and
      radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK
      transfected fibroblasts admixed with type-1 dendritic cells (DC) loaded with
      autologous tumor lysate. The participants were evaluated for occurrence of
      adverse events, immune response, and clinical response by radiological imaging.
      RESULTS AND DISCUSSION: In UPCI 95-033, only 2 of 6 participants received the
      vaccinations. Four other participants were withdrawn from the trial because of
      tumor progression prior to production of the cellular vaccine. However, both
      participants who received two vaccinations demonstrated encouraging immunological
      and clinical responses. Biopsies from the local vaccine sites from one
      participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T
      cells. Interferon (IFN)-gamma Enzyme-Linked Immuno-SPOT (ELISPOT) assay in
      another human leukocyte antigen (HLA)-A2+ participant demonstrated systemic T
      cell responses against an HLA-A2-restricted glioma-associated antigen (GAA)
      epitope EphA2883-891. Moreover, both participants demonstrated clinical and
      radiological improvement with no evidence of allergic encephalitis, although both
      participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6
      enrolled participants received scheduled vaccinations with no incidence of major
      adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment
      was well tolerated; however, we were unable to observe detectable IFN-gamma post
      vaccine responses or prolonged progression-free survival in these participants.
      CONCLUSION: Feasibility challenges inherent in the generation of a patient
      specific gene transfection-based vaccine strongly suggests the need for more
      practical formulations that would allow for the timely administration of
      vaccines. Nevertheless, successful generation of type-1 DCs and preliminary
      safety in the current study provide a strong rationale for further efforts to
      develop novel glioma vaccines.

PMID- 18093336
TI  - Spontaneous immune responses against glioma-associated antigens in a long term
      survivor with malignant glioma.
AB  - BACKGROUND: In patients with high grade glioma, little is known regarding
      existence of naturally occurring adaptive T cell reactivity against glioma
      associated antigens (GAAs). In this report, we characterized GAA-specific CD8+ T
      cells and innate immune cells in a patient who has survived with anaplastic
      astrocytoma (AA) for over 12 years without recurrence. METHODS: Peripheral blood
      mononuclear cells (PBMCs) derived from the long term survivor with AA were
      evaluated for the frequency, cytotoxic T lymphocyte (CTL) activity and
      differentiation status of CD8+ cells recognizing GAA-derived epitopes as well as
      relative numbers of other immune cell subsets. This patient's AA tissue was
      evaluated for expression of two GAAs EphA2 and interleukin-13 receptor alpha2
      subunit (IL-13Ralpha2) by immunohistochemistry. RESULTS: The patient's tumor
      expressed both EphA2 and IL-13Ralpha2, and in vitro stimulated PBMC demonstrated
      superior EphA2883-891 and IL-13Ralpha2345-353-specific CTL reactivity compared to
      PBMC samples from two other patients with progressing malignant glioma.
      Unstimulated EphA2883-891-reactive CD8+ T cells contained high numbers of CD45RA
      /CCR7- late effector and CD45RA-/CCR7+ central memory cells. Among other
      leukocyte subsets, elevated numbers of NK-T cells were found. CONCLUSION: To our
      knowledge, the current study is one of the first demonstrating the presence of
      antigen-experienced, GAA-reactive CD8+ T cells in a patient who has survived with
      AA for over 12 years without recurrence. Further studies are warranted to
      determine whether the status of GAA-reactive CD8+ T cells dictates survival of
      patients and/or response to therapeutic vaccines.

PMID- 18093337
TI  - Can pill placebo augment cognitive-behavior therapy for panic disorder?
AB  - BACKGROUND: In a number of drug and psychotherapy comparative trials,
      psychotherapy-placebo combination has been assumed to represent psychotherapy.
      Whether psychotherapy plus pill placebo is the same as psychotherapy alone is an
      empirical question which however has to date never been examined systematically.
      METHODS: We conducted a systematic review and meta-analysis of randomised
      controlled trials (RCTs) that directly compared cognitive-behavior therapy (CBT)
      alone against CBT plus pill placebo in the treatment of panic disorder. RESULTS:
      Extensive literature search was able to identify three relevant RCTs. At the end
      of the acute phase treatment, patients who received CBT plus placebo had 26%
      (95%CI: 2 to 55%) increased chances of responding than those who received CBT
      alone. At follow-up the difference was no longer statistically significant (22%,
      95%CI: -10% to 64%). CONCLUSION: The act of taking a pill placebo may enhance the
      placebo effect already contained in the effective psychotherapeutic intervention
      during the acute phase treatment. Theoretically this is an argument against the
      recently claimed null hypothesis of placebo effect in general and clinically it
      may point to some further room for enhancing the psychotherapeutic approach for
      panic disorder.

PMID- 18093338
TI  - Rice transposable elements are characterized by various methylation environments
      in the genome.
AB  - BACKGROUND: Recent studies using high-throughput methods have revealed that
      transposable elements (TEs) are a comprehensive target for DNA methylation.
      However, the relationship between TEs and their genomic environment regarding
      methylation still remains unclear. The rice genome contains representatives of
      all known TE families with different characteristics of chromosomal distribution,
      structure, transposition, size, and copy number. Here we studied the DNA
      methylation state around 12 TEs in nine genomic DNAs from cultivated rice strains
      and their closely related wild strains. RESULTS: We employed a transposon display
      (TD) method to analyze the methylation environments in the genomes. The 12 TE
      families, consisting of four class I elements, seven class II elements, and one
      element of a different class, were differentially distributed in the rice
      chromosomes: some elements were concentrated in the centromeric or
      pericentromeric regions, but others were located in euchromatic regions. The TD
      analyses revealed that the TE families were embedded in flanking sequences with
      different methylation degrees. Each TE had flanking sequences with similar
      degrees of methylation among the nine rice strains. The class I elements tended
      to be present in highly methylated regions, while those of the class II elements
      showed widely varying degrees of methylation. In some TE families, the degrees of
      methylation were markedly lower than the average methylation state of the genome.
      In two families, dramatic changes of the methylation state occurred depending on
      the distance from the TE. CONCLUSION: Our results demonstrate that the TE
      families in the rice genomes can be characterized by the methylation states of
      their surroundings. The copy number and degree of conservation of the TE family
      are not likely to be correlated with the degree of methylation. We discuss
      possible relationships between the methylation state of TEs and their
      surroundings. This is the first report demonstrating that TEs in the genome are
      associated with a particular methylation environment that is a feature of a given
      TE.

PMID- 18093339
TI  - Maintenance of transposon-free regions throughout vertebrate evolution.
AB  - BACKGROUND: We recently reported the existence of large numbers of regions up to
      80 kb long that lack transposon insertions in the human, mouse and opossum
      genomes. These regions are significantly associated with loci involved in
      developmental and transcriptional regulation. RESULTS: Here we report that
      transposon-free regions (TFRs) are prominent genomic features of amphibian and
      fish lineages, and that many have been maintained throughout vertebrate
      evolution, although most transposon-derived sequences have entered these lineages
      after their divergence. The zebrafish genome contains 470 TFRs over 10 kb and a
      further 3,951 TFRs over 5 kb, which is comparable to the number identified in
      mammals. Two thirds of zebrafish TFRs over 10 kb are orthologous to TFRs in at
      least one mammal, and many have orthologous TFRs in all three mammalian genomes
      as well as in the genome of Xenopus tropicalis. This indicates that the mechanism
      responsible for the maintenance of TFRs has been active at these loci for over
      450 million years. However, the majority of TFR bases cannot be aligned between
      distantly related species, demonstrating that TFRs are not the by-product of
      strong primary sequence conservation. Syntenically conserved TFRs are also more
      enriched for regulatory genes compared to lineage-specific TFRs. CONCLUSION: We
      suggest that TFRs contain extended regulatory sequences that contribute to the
      precise expression of genes central to early vertebrate development, and can be
      used as predictors of important regulatory regions.

PMID- 18093340
TI  - Osteopetrotic (op/op) mice have reduced microglia, no Abeta deposition, and no
      changes in dopaminergic neurons.
AB  - BACKGROUND: Activation of microglia is a part of the inflammatory response in
      neurodegenerative diseases but its role in the pathophysiology of these diseases
      is still unclear. The osteopetrotic (op/op) mouse lacks colony-stimulating factor
      1 (CSF-1) and thus has a deficiency in microglia and macrophages. Prior reports
      have demonstrated that op/op mice deposit amyloid beta (Abeta) plaques, similar
      to those found in Alzheimer's disease. The purpose of these studies was to
      confirm this and to determine if the lack of CSF-1 affects the development of
      dopaminergic neurons and the expression of CD200, a known microglial inhibitory
      protein. METHOD: We examined the central nervous system of op/op mice at 30 days,
      60 days and 7 months of age and wildtype littermates at 30 days using
      immunohistochemistry and histochemistry. RESULTS: We found a decrease in the
      number of microglia in 1 month-old op/op mice compared to wildtype (WT)
      littermates as measured by CD11b, CD45, CD32/16, CD68, CD204 and F4/80
      immunoreactivity. Abeta plaques were not detected, while the number of
      dopaminergic neurons appeared normal. The expression of CD200 appeared to be
      normal, but there appeared to be a lower expression in the substantia nigra.
      CONCLUSION: In contrast to a prior report we did not detect Abeta deposition in
      the central nervous system of op/op mice at 30 days, 60 days or 7 months of age
      and there was a normal number of dopaminergic neurons. This indicates that op/op
      mice may be useful to examine the effects of microglia on neurodegenerative
      disease progression by breeding them to different transgenic mouse models. In
      addition, the lack of CSF-1 does not appear to affect CD200 expression by neurons
      but we did note a decrease in the substantia nigra of op/op and WT mice,
      suggesting that this may be a mechanism by which microglia control may be
      attenuated in this specific area during Parkinson's disease.

PMID- 18093341
TI  - Sequential solvent extraction for the modes of occurrence of selenium in coals of
      different ranks from the Huaibei Coalfield, China.
AB  - Forms of selenium in bituminous coal, anthracite, and cokeite (natural coke) from
      Huaibei Coalfield, Anhui, China, have been determined by sequential solvent
      extraction. The selenium content in bulk samples is 4.0, 2.4, and 2.0 microg/g in
      bituminous coal, anthracite, and cokeite, respectively. The six forms of selenium
      determined by six-step solvent extraction are water-leachable, ion-exchangeable,
      organic matter-associated, carbonate-associated, silicate-associated, and sulfide
      associated. The predominant forms of selenium in bituminous coal are organic
      matter-associated (39.0%), sulfide-associated (21.1%), and silicate bound
      (31.8%); these three forms account for 92% of the total. The organic matter bound
      selenium decrease dramatically from bituminous coal (39.0%) to anthracite (11.6%)
      and to cokeite (0%), indicating that organic matter bound selenium is converted
      to other forms during metamorphism of the coal, most likely sulfide-form. The
      sulfide-associated form increased remarkably from bituminous coal (21.1%) to
      anthracite (50.4%) and cokeite (54.5%), indicating the formation of selenium
      sulfide, possibly in pyrite during the transformation of bituminous coal to
      anthracite and cokeite. The silicate-associated selenium in bituminous coal
      (31.8%) is much higher than that in anthracite (16.4%) and cokeite (15.8%),
      indicating that silicate-associated selenium is partly converted to sulfide
      during metamorphism.

PMID- 18093342
TI  - Effective selection of informative SNPs and classification on the HapMap genotype
      data.
AB  - BACKGROUND: Since the single nucleotide polymorphisms (SNPs) are genetic
      variations which determine the difference between any two unrelated individuals,
      the SNPs can be used to identify the correct source population of an individual.
      For efficient population identification with the HapMap genotype data, as few
      informative SNPs as possible are required from the original 4 million SNPs.
      Recently, Park et al. (2006) adopted the nearest shrunken centroid method to
      classify the three populations, i.e., Utah residents with ancestry from Northern
      and Western Europe (CEU), Yoruba in Ibadan, Nigeria in West Africa (YRI), and Han
      Chinese in Beijing together with Japanese in Tokyo (CHB+JPT), from which 100,736
      SNPs were obtained and the top 82 SNPs could completely classify the three
      populations. RESULTS: In this paper, we propose to first rank each feature (SNP)
      using a ranking measure, i.e., a modified t-test or F-statistics. Then from the
      ranking list, we form different feature subsets by sequentially choosing
      different numbers of features (e.g., 1, 2, 3, ..., 100.) with top ranking values,
      train and test them by a classifier, e.g., the support vector machine (SVM),
      thereby finding one subset which has the highest classification accuracy.
      Compared to the classification method of Park et al., we obtain a better result,
      i.e., good classification of the 3 populations using on average 64 SNPs.
      CONCLUSION: Experimental results show that the both of the modified t-test and F
      statistics method are very effective in ranking SNPs about their classification
      capabilities. Combined with the SVM classifier, a desirable feature subset (with
      the minimum size and most informativeness) can be quickly found in the greedy
      manner after ranking all SNPs. Our method is able to identify a very small number
      of important SNPs that can determine the populations of individuals.

PMID- 18093343
TI  - Effect of apple cider vinegar on delayed gastric emptying in patients with type 1
      diabetes mellitus: a pilot study.
AB  - BACKGROUND: Previous studies on healthy people show that vinegar delays gastric
      emptying and lowers postprandial blood glucose and insulin levels. The aim of
      this study was to investigate the effect of apple cider vinegar on delayed
      gastric emptying rate on diabetes mellitus patients. METHODS: Ten patients with
      type 1 diabetes and diabetic gastroparesis, including one patient who had
      undergone vagotomy, were included and completed the investigator blinded
      crossover trial. The gastric emptying rate (GER) was measured using standardized
      real-time ultrasonography. The GER was calculated as the percentage change in the
      antral cross-sectional area 15 and 90 minutes after ingestion of 300 g rice
      pudding and 200 ml water (GER1), or 300 g rice pudding and 200 ml water with 30
      ml apple cider vinegar (GER2). The subjects drank 200 ml water daily before
      breakfast one week before the measurement of GER1. The same subjects drank 200 ml
      water with 30 ml vinegar daily before breakfast for two weeks before the
      measurement of GER2. RESULTS: The median values of GER1 and GER2 were 27% and
      17%, respectively. The effect of vinegar on the rate of gastric emptying was
      statistically significant (p < 0.05). CONCLUSION: This study shows that vinegar
      affects insulin-dependent diabetes mellitus patients with diabetic gastroparesis
      by reducing the gastric emptying rate even further, and this might be a
      disadvantage regarding to their glycaemic control. TRIAL REGISTRATION NUMBER:
      ISRCTN33841495.

PMID- 18093344
TI  - Relative quantification of mRNA: comparison of methods currently used for real
      time PCR data analysis.
AB  - BACKGROUND: Fluorescent data obtained from real-time PCR must be processed by
      some method of data analysis to obtain the relative quantity of target mRNA. The
      method chosen for data analysis can strongly influence results of the
      quantification. RESULTS: To compare the performance of six techniques which are
      currently used for analysing fluorescent data in real-time PCR relative
      quantification, we quantified four cytokine transcripts (IL-1beta, IL-6 TNF
      alpha, and GM-CSF) in an in vivo model of colonic inflammation. Accuracy of the
      methods was tested by quantification on samples with known relative amounts of
      target mRNAs. Reproducibility of the methods was estimated by the determination
      of the intra-assay and inter-assay variability. Cytokine expression normalized to
      the expression of three reference genes (ACTB, HPRT, SDHA) was then determined
      using the six methods for data analysis. The best results were obtained with the
      relative standard curve method, comparative Ct method and with DART-PCR,
      LinRegPCR and Liu & Saint exponential methods when average amplification
      efficiency was used. The use of individual amplification efficiencies in DART
      PCR, LinRegPCR and Liu & Saint exponential methods significantly impaired the
      results. The sigmoid curve-fitting (SCF) method produced medium performance; the
      results indicate that the use of appropriate type of fluorescence data and in
      some instances manual selection of the number of amplification cycles included in
      the analysis is necessary when the SCF method is applied. We also compared
      amplification efficiencies (E) and found that although the E values determined by
      different methods of analysis were not identical, all the methods were capable to
      identify two genes whose E values significantly differed from other genes.
      CONCLUSION: Our results show that all the tested methods can provide quantitative
      values reflecting the amounts of measured mRNA in samples, but they differ in
      their accuracy and reproducibility. Selection of the appropriate method can also
      depend on the design of a particular experiment. The advantages and disadvantages
      of the methods in different applications are discussed.

PMID- 18093345
TI  - Proliferating and differentiating effects of three different growth factors on
      pluripotent mesenchymal cells and osteoblast like cells.
AB  - Growth factors are in clinical use to stimulate bone growth and regeneration. BMP
      2 is used in long bone and spinal surgery, PDGFbb for the treatment of
      periodontal defects and children with growth hormone receptor deficiency are
      treated with IGF-I.Aim of the present study was the comparative analysis of the
      effect of these growth factors released from a local drug delivery system on
      cells of the osteogenic lineage at differing differentiation stages.The
      experiments with the mesenchymal cell line C2C12 revealed a proliferating effect
      of all three growth factors and a differentiating effect of BMP-2 with a dramatic
      increase in alkaline phosphatase activity. None of the growth factors stimulated
      cell migration.Human osteoblast like cells showed similar results with an
      increase in proliferation after stimulation with IGF-I or PDGFbb. The enzymatic
      activity of alkaline phosphatase was enhanced only in the cells stimulated with
      BMP-2. This group showed also more mineralized matrix compared to the other
      groups.In conclusion, the growth factors IGF-I and PDGFbb delivered with a local
      drug delivery system stimulated cell proliferation, whereas BMP-2 showed a
      dramatic effect on differentiation on osteoblast precursor cells and osteoblast
      like cells.

PMID- 18093346
TI  - Neonatal mortality in the empowered action group states of India: trends and
      determinants.
AB  - In India, the eight socioeconomically backward states of Bihar, Chhattisgarh,
      Jharkhand, Madhya Pradesh, Orissa, Rajasthan, Uttaranchal and Uttar Pradesh,
      referred to as the Empowered Action Group (EAG) states, lag behind in the
      demographic transition and have the highest infant mortality rates in the
      country. Neonatal mortality constitutes about 60% of the total infant mortality
      in India and is highest in the EAG states. This study assesses the levels and
      trends in neonatal mortality in the EAG states and examines the impact of bio
      demographic compared with health care determinants on neonatal mortality. Data
      from India's Sample Registration System (SRS) and National Family and Health
      Survey (NFHS-2, 1998-99) are used. Cox proportional hazard models are applied to
      estimate adjusted neonatal mortality rates by health care, bio-demographic and
      socioeconomic determinants. Variations in neonatal mortality by these
      determinants suggest that universal coverage of all pregnant women with full
      antenatal care, providing assistance at delivery and postnatal care including
      emergency care are critical inputs for achieving a reduction in neonatal
      mortality. Health interventions are also required that focus on curtailing the
      high risk of neonatal deaths arising from the mothers' younger age at childbirth,
      low birth weight of children and higher order births with short birth intervals.

PMID- 18093347
TI  - Inter-generation social mobility modifies framingham risk score in Polish middle
      aged men, but not in women.
AB  - In modern societies, there are regular social gradients in most health
      parameters, and also in the structure of morbidity and mortality. However, the
      significance of inter-generation social mobility for general health status still
      remains equivocal. This study was therefore performed in order to compare the
      effect of social mobility on coronary heart disease (CHD) risk between middle
      aged Polish men and women. A total of 342 men and 458 women, aged 40 and 50 and
      inhabitants of Wroclaw, were examined. Risk of CHD was estimated using the
      Framingham Risk Score (FRS), calculated for each individual. Social mobility was
      defined as an inter-generation change in social status expressed as educational
      level between the examined individual and his/her father. Using two-variable
      regression models, it was demonstrated that FRS in men was determined by both
      their father's education level (beta=0.33, p<0.0001) and inter-generation change
      in educational status (beta=0.18, p=0.008). In contrast, FRS in women was related
      only to their father's education level (beta=0.35, p<0.0001), but not to inter
      generation social mobility (beta=0.35, p=0.25). In particular, an incremental
      change in educational level among those men whose father had finished primary
      school at the very most or among those whose father had finished basic trade
      school was accompanied by a significant decrease in FRS (F=4.12, p=0.009 and
      F=3.25, p=0.04, respectively). It is concluded that inter-generation social
      mobility modifies CHD risk (as estimated using FRS) in middle-aged Polish men,
      but not in women. The precise mechanisms responsible for the observed sex
      difference in this phenomenon need to be established in further studies.

PMID- 18093348
TI  - Childlessness predicts helping of nieces and nephews in United States, 1910.
AB  - The 'helpers at the nest' hypothesis suggests that individuals who are not
      currently reproducing often help kin by caretaking and thereby increase their
      inclusive fitness. Using a large scale historical dataset (Integrated Public Use
      Microdata Series sample of 1910; n=13,935), the hypothesis is tested that
      childless couples are more likely to fulfil such a role by taking care of a niece
      or nephew, but not a parent, than couples with children. Childless couples were
      significantly more likely to take care of a niece or nephew than couples with
      children. In contrast, couples with children and childless couples did not differ
      in caretaking of parents. Childless couples were also more likely to have more
      and younger nieces/nephews in their home than couples with children.

PMID- 18093349
TI  - Pathways into childlessness: evidence of gendered life course dynamics.
AB  - Using data from the first wave of the Netherlands Kinship Panel Study (NKPS) for
      2867 women and 2195 men aged 40 to 79, this study examines to what extent
      educational, employment and marital pathways shape the likelihood of remaining
      childless, and whether these pathways are gendered. The findings indicate that
      women and men have distinctive pathways into childlessness. Educational
      attainment increases the likelihood of remaining childless among women only. A
      stable career increases the likelihood of remaining childless among women, but it
      increases the likelihood of entering fatherhood. Years without a partner is
      positively associated with childlessness among both women and men. Not having had
      a partnership and having had multiple partnerships are strong determinants of
      childlessness, especially among men.

PMID- 18093350
TI  - A novel member of the ligand-gated chloride channel gene family from Haemonchus
      contortus.
AB  - Ligand-gated chloride channels (LGCCs) are key components of the nervous system
      of parasitic nematodes and important targets for anthelmintics. Here, we describe
      the isolation and characterization of a novel member of the LGCC gene family
      (HcLGCC1) from the parasitic nematode Haemonchus contortus. Sequence analysis
      revealed that the channel subunit encoded by HcLGCC1 is anion selective and a
      member of a group of channels characterized as having two Cys-loops in the N
      terminal ligand-binding domain. Although the overall function of HcLGCC1 is
      presently unknown, the gene may play a key role in the early developmental stages
      of the parasite. Further investigations into the function of LGCCs, such as
      HcLGCC1, in parasitic nematodes should have implications for the discovery of new
      anthelmintic targets.

PMID- 18093351
TI  - A pilot survey of socio-economic differences in child-feeding behaviours among
      parents of primary-school children.
AB  - OBJECTIVE: Parents food choices and weight, but little is known about the social
      class distribution of parent self-reported child-feeding behaviours in two socio
      economically contrasting areas. DESIGN: A cross-sectional survey using the
      Parental Feeding Style Questionnaire. Mean scores were calculated for five child
      feeding behaviours: control over eating, emotional feeding,
      encouragement/prompting, instrumental feeding and restriction. Parents behaviours
      that might be used to directly influence children's food intake and weight.
      CONCLUSIONS: Child-feeding behaviours differ between areas within a single city
      and within a largely white population, and this distribution is related to socio
      economic and educational factors. Experimental and longitudinal studies are
      needed to further investigate the potential role of child-feeding behaviours in
      childhood overweight and obesity.

PMID- 18093352
TI  - The association between consumption of breakfast cereals and BMI in
      schoolchildren aged 12-17 years: the VYRONAS study.
AB  - OBJECTIVE: To evaluate whether consumption of breakfast cereals is associated
      with BMI in a sample of Greek adolescents. DESIGN: A cross-sectional health and
      nutrition survey. SETTING AND SUBJECTS: During 2004-5, 2008 schoolchildren aged
      12-17 years were selected from twelve schools located in Vyronas region (Athens
      metropolitan area). Height and weight were measured and BMI was calculated. A
      semiquantitative FFQ was applied and multiple logistic regression analysis was
      used. RESULTS: Overall, 4.7% of boys and 1.7% of girls were obese, whereas 19.4%
      of boys and 13.2% of girls were overweight. Only 20.7% of boys and 15.5% of girls
      reported that they consume cereals as a first choice for breakfast. Consumption
      of breakfast cereals was associated with lower BMI in boys (P=0.08) and
      girls(P=0.019), irrespective of age and physical activity status. More prominent
      results were observed for daily cereal consumption or for more than two daily
      servings of cereals consumed for breakfast. Consumption of pre-sweetened
      breakfast cereals was associated with lower BMI compared with non-pre-sweetened
      or no intake of cereals, in both genders (P<0.001). Consumption of breakfast
      cereals was associated with 33% (95% CI 14%, 48%) lower likelihood of
      overweight/obesity, irrespective of age, sex and physical activity status.
      CONCLUSIONS: Consumption of breakfast cereals was associated with lower BMI
      levels and a lower likelihood of overweight/obesity in both genders; thus a solid
      basis for public health professionals could be built when issuing advice on
      weight management.

PMID- 18093353
TI  - Calcium, nutrient and food intake of Greek Orthodox Christian monks during a
      fasting and non-fasting week.
AB  - OBJECTIVE: To assess the Ca, nutrient and food intake of Greek Orthodox Christian
      monks during a vegetarian-type fasting week, compared with their normal diet.
      DESIGN: Dietary data collection (using 7 d weighed food records), anthropometric
      and blood pressure measurements, as well as serum glucose and lipid analyses,
      were performed during Palm Sunday week (fasting) and the week following Pentecost
      Sunday (non-fasting). Mean daily nutrient and food (g/d) intakes were calculated
      from the food records. SETTING: The study took place in two monasteries in the
      Municipality of Heraklion, Crete. SUBJECTS: The study involved ten healthy monks
      aged 25-65 years, with BMI > 30 kg/m2, who had been performing fasts for the last
      24.4 (SD 10.4) years and lived in monasteries in Crete during April-June 2005.
      RESULTS: Nutrient and food intake profiles were more favourable during the
      fasting week, when participants had lower intakes of total and saturated fat and
      trans-fatty acids, and higher intakes of dietary fibre, Fe, folate, legumes and
      fish/seafood. Ca intake was lower when participants fasted, whereas consumption
      of dairy products, meat and eggs increased significantly in the non-fasting week.
      Systolic blood pressure was significantly higher, whereas blood lipid levels were
      more favourable during the fasting week. CONCLUSIONS: The periodic vegetarianism
      recommended by the Greek Orthodox Church contributes to the favourable profiles
      of several biomarkers of health among this sample of monks. The fasting rituals
      described are an important component of the traditional diet of Crete and should
      be emphasised in nutrition education programmes promoting this Mediterranean
      eating pattern.

PMID- 18093354
TI  - Detection of cardio-metabolic risk by BMI and waist circumference among a
      population of Guatemalan adults.
AB  - BACKGROUND: BMI and waist circumference (WC) are used to screen for cardio
      metabolic risk; however it is unclear how well these indices perform in
      populations subject to childhood stunting. OBJECTIVES: To evaluate BMI and WC as
      indicators of cardio-metabolic risk and to determine optimal cut-off points among
      1,325 Guatemalan adults (44 % stunted: 162 cm men). METHODS: Cardio-metabolic
      risk factors were systolic/diastolic blood pressure 85 mmHg, glucose 5 mmol/l,
      TAG 7 mmol/l, ratio of total cholesterol to HDL-cholesterol 0, and the presence
      of two or more and three or more of the preceding risk factors. Receiver
      operating characteristic (ROC) curve analysis was used. RESULTS: Areas under the
      ROC curve were in the range of 005978 for WC among men and 006472 among women,
      respectively. Optimal cut-off points for BMI were 242651 kg/m2 stunted; 242656
      kg/m2 among women (262769 kg/m2 non-stunted). Optimal cut-off points for WC were
      879134 cm stunted; 889333 cm among women (909486 cm non-stunted). CONCLUSION:
      Optimal cut-off points for BMI were slightly higher among women than men with no
      meaningful differences by stature. Optimal cut-off points for WC were several
      centimetres lower for stunted compared with non-stunted men, and both were
      substantially lower than the current recommendations among Western populations.
      Cut-off points derived from Western populations may not be appropriate for
      developing countries with a high prevalence of stunting.

PMID- 18093355
TI  - Atresia of the aortic arch, with a collateral artery from the right subclavian
      artery supplying the descending aorta.
AB  - An infant of 2 months presented with absence of the femoral pulses, albeit with
      no signs of cardiac failure. The mother was known to have ingested Valproate
      during pregnancy. Echocardiography showed the aortic arch to be interrupted
      between the left common carotid and left subclavian arteries, so-called type B
      interruption, in the setting of an intact ventricular septum. Angiography, and
      multislice computed tomography, revealed the descending aorta to be supplied by a
      collateral artery originating from the right subclavian artery. Corrective
      surgery was successfully performed, but revealed an atretic segment of the arch
      at the site of interruption of flow.

PMID- 18093356
TI  - Can analysis of the bispectral index prove helpful when monitoring titration of
      doses of midazolam and ketamine for sedation during paediatric cardiac
      catheterization.
AB  - OBJECTIVE: We investigated the use of the bispectral index for monitoring
      sedation during cardiac catheterization. The scores for the bispectral index may
      not reflect correct values in children, but may be helpful during titration of
      sedatives such as midazolam and ketamine. METHODS: We conducted a prospective
      randomized clinical trial in 126 patients scheduled for cardiac catheterization
      in a teaching hospital. They ranged in age from 4 months to 15 years. In 66
      patients, sedation was performed without use of the bispectral index, while the
      index was used in the other 60 patients. The data collected included heart rate,
      mean arterial pressure, respiratory rate, saturation of oxygen, amount of
      sedatives, awakening time and adverse effects. We subdivided the patients into
      age-related groups for each parameter. RESULTS: The demographic data were not
      statistically different. Monitoring with the bispectral index in those aged from
      1 to 3 years revealed use of lower doses of midazolam, at 2.09 mg per kg per hr,
      with standard deviation of 0.36, and similarly lowers doses of ketamine, at 2.07
      mg per kg per hr, with standard deviation of 0.22, the values in those not
      monitored being 2.93, with standard deviation of 0.45, and 2.96 with standard
      deviation of 0.51 respectively, these difference being statistically significant
      (p = 0.001 and p = 0.04, respectively). In those aged from 3 to 6 years of age,
      dosage of midazolam was 2.09, with deviation of 0.36, and of ketamine 1.78, with
      deviation of 0.27, following use of the bispectral index, compared to 2.89 with
      deviation of 0.28, and 2.62 with deviation of 0.69 respectively, when the
      bispectral index was not used, these again being significant differences (p =
      0.033 and p = 0.04). The requirements for respiratory support and adverse effects
      were also significantly lower when using the bispectral index (p less than 0.05).
      No significant difference was found regarding dosages at the ages of 4 months to
      1 year, and 6 to 15 years. The awakening time, however, was shorter with use of
      the index in those aged from 1 to 6 years. CONCLUSIONS: When using the bispectral
      index for monitoring sedation during catheterization in children, we noted
      decreased need for doses of midazolam and ketamine, a lower need for respiratory
      support and less adverse effects.

PMID- 18093357
TI  - Electrocardiographic and echocardiographic findings in street children known to
      be substance abusers.
AB  - Substance abuse is prevalent in adolescent street children, and death is reported
      as secondary to aspiration, accidental trauma, asphyxia, cardiac arrhythmia,
      anoxia, vagal inhibition and respiratory depression. In this study, we examined
      electrocardiographic and echocardiographic findings from 53 street male
      adolescents, comparing our findings to those obtained from 61 controls in the
      same age group. The street children smoked cigarettes (98.1%) and had used, or
      were using, thinner (73.6%), glue (75.5%), hashish (79.2%), morphine or its
      products (24.5%), ecstasy (37.7%), anti-emetics (13.2%) and alcohol (60.4%). On
      examination, their blood pressures were lower than the control group.
      Electrocardiographically, PR, QRS, QT were found to be longer (p less than 0.05)
      than the values for healthy controls. Although it was not statistically
      significant, QTc duration was also longer than the control group.
      Echocardiography revealed increased diameters of the left ventricle and atrium,
      the aorta, and the coronary arteries as compared to the healthy children (p less
      than 0.05).

PMID- 18093358
TI  - Altered endothelial function following the Fontan procedure.
AB  - OBJECTIVE: Thrombosis has been widely described after the Fontan procedure. The
      vascular endothelium plays a central role in the control of coagulation and
      fibrinolysis. The aim of this study was to investigate if patients undergoing a
      modified Fontan procedure have impaired endothelial function and fibrinolysis in
      the late postoperative course. PATIENTS AND METHODS: We compared 23 patients aged
      from 7 to 26 years with age-matched healthy volunteers, collecting blood samples
      prior to and following standardized venous occlusion testing. Plasma levels of
      von Willebrand factor antigen, tissue-type plasminogen activator antigen,
      plasminogen activator inhibitor-1, and D-dimer were measured with enzyme-linked
      immunosorbent assay. RESULTS: We found increased plasma levels of von Willebrand
      factor antigen in patients when compared to controls (p = 0.003). At the basal
      condition, concentrations of tissue-type plasminogen activator antigen and
      plasminogen activator inhibitor-1 antigen in the plasma, as well as their
      activity, were not significantly different between patients and controls.
      Following venous occlusion, concentrations of tissue-type plasminogen activator
      antigen in the plasma were significantly increased both in patients and controls,
      compared to pre-occlusion values. D-dimer was within the reference range.
      Multivariate discriminant analysis differentiated patients and their controls on
      the basis of differences for plasminogen activator inhibitor-1 and von Willebrand
      factor antigen (p = 0.0016). CONCLUSIONS: Our data suggest that patients with the
      Fontan circulation may have endothelial dysfunction, as indicated by raised
      levels of von Willebrand factor. Fibrinolysis seems to be relatively preserved,
      as suggested by appropriate response to venous occlusion.

PMID- 18093359
TI  - The effect of age and gender on the electrocardiogram in children.
AB  - Our aim was to determine, using a computer program for measurement and analysis,
      the effects, if any, of age and gender on the electrocardiographic measurements
      in a large cohort of Turkish children. We analyzed standard simultaneous 12-lead
      electrocardiograms from 2241 healthy Turkish children, aged from 1 day to 16
      years, to calculate limits of normality of a variety of electrocardiographic
      measurements for 12 age groups. Clinically significant differences were shown to
      exist, and the results compared with previously established normal limits.
      Differences were demonstrated for gender in measurements of both amplitude and
      duration, particularly in the adolescent period. We have provided tables and
      figures showing age and gender-dependent means and upper limits of normal
      electrocardiographic parameters for the important leads.

PMID- 18093360
TI  - Factors prolonging length of stay in the cardiac intensive care unit following
      the arterial switch operation.
AB  - The arterial switch operation has become the preferred procedure for surgical
      management of transposition, defined on the basis of concordant atrioventricular
      and discordant ventriculo-arterial connections. We conducted a retrospective
      evaluation of our experience in 61 infants with this segmental combination, seen
      from January, 1997, to July, 2003, in order to determine the factors that are
      associated with a prolonged postoperative course. Factors independently
      associated with a prolonged postoperative stay in the cardiac intensive care unit
      included prematurity, difficulty in feeding, capillary leak, need for
      preoperative inotropic support, and postoperative infectious complications.
      Future research is warranted designed to minimize the impact of capillary leak
      and postoperative infectious complications. In addition, based on these results,
      our practice has evolved to initiate enteral feedings in the preoperative period
      if feasible, with such enteral feedings resumed as soon as possible following
      surgery.

PMID- 18093361
TI  - What is the preferred therapy for patients with aortic coarctation--the standard
      gamble and decision analysis versus real results?

PMID- 18093362
TI  - Are children with congenital cardiac malformations at increased risk of deficits
      in social cognition?
AB  - In this review, I summarize observations suggesting that social cognition
      deficits are an important element of the neurodevelopmental morbidities of
      children with congenital cardiac malformations. Referred to as "theory of mind"
      deficits, they pertain to the ability to "read" other people, that is, to infer
      their internal states and thus to interpret their actions appropriately. I also
      hypothesize that children with such congenital cardiac malformations have
      difficulty identifying and describing their own internal states, which is
      referred to as alexithymia. These hypotheses are based on data collected as part
      of a prospective study of the neurologic outcomes of children with concordant
      atrioventricular and discordant ventriculo-arterial connections, or
      transposition. On a variety of tasks that assess pragmatic language and discourse
      skills, such as elicited personal narratives, free play with a parent, and
      written narratives, the children consistently performed below age-expected levels
      and in ways that suggested the presence of "theory of mind" deficits. Their
      narratives lacked coherence, failed to include critical information required by a
      listener, and made infrequent reference to internal states. In ongoing
      evaluations of the children as adolescents, we are testing these hypotheses more
      systematically by administering several instruments specifically developed to
      assess "theory of mind" and alexithymia.

PMID- 18093363
TI  - The high burden of rheumatic heart disease found on autopsy in Fiji.
AB  - Rheumatic heart disease causes more than 200,000 deaths worldwide annually, with
      the vast majority of these deaths occurring in developing countries, yet there
      are few autopsy studies of rheumatic heart disease in these countries. We
      performed a retrospective review of 6218 autopsies performed during the period
      from 1990 through 2006, searching for cases of rheumatic heart disease based upon
      the macroscopic pathologic examination of the heart. We found 147 cases (2.4%) of
      rheumatic heart disease. There was an apparent increase in the number of cases in
      the past 5 years. There were 95 deaths that were directly attributable to
      rheumatic heart disease, with congestive cardiac failure being the most common
      cause of death in 75 cases. The mean age at death due to rheumatic heart disease
      was 38 years. There were more cases of rheumatic heart disease in Indigenous
      Fijians than Indo-Fijians, with an adjusted relative risk of 1.26 (95% confidence
      intervals from 0.87 to 1.86). Our findings reflect the high burden and early age
      of death due to rheumatic heart disease in Fiji and the Pacific region generally,
      and underline the need for early detection and adequate secondary penicillin
      prophylaxis in this region.

PMID- 18093364
TI  - 5th EuroNeuro 2008. Maastricht, The Netherlands. January 16-19, 2008. Abstracts.

PMID- 18093365
TI  - Retinal bipolar cells: temporal filtering of signals from cone photoreceptors.
AB  - The temporal dynamics of the response of neurons in the outer retina were
      investigated by intracellular recording from cones, bipolar, and horizontal cells
      in the intact, light-adapted retina of the tiger salamander (Ambystoma tigrinum),
      with special emphasis on comparing the two major classes of bipolars cells, the
      ON depolarizing bipolars (Bd) and the OFF hyperpolarizing bipolars (Bh). Transfer
      functions were computed from impulse responses evoked by a brief light flash on a
      steady background of 20 cd/m(2). Phase delays ranged from about 89 ms for cones
      to 170 ms for Bd cells, yielding delays relative to that of cones of about 49 ms
      for Bh cells and 81 ms for Bd cells. The difference between Bd and Bh cells,
      which may be due to a delay introduced by the second messenger G-protein pathway
      unique to Bd cells, was further quantified by latency measurements and responses
      to white noise. The amplitude transfer functions of the outer retinal neurons
      varied with light adaptation in qualitative agreement with results for other
      vertebrates and human vision. The transfer functions at 20 cd/m(2) were
      predominantly low pass with 10-fold attenuation at about 13, 14, 9.1, and 7.7 Hz
      for cones, horizontal, Bh, and Bd cells, respectively. The transfer function from
      the cone voltage to the bipolar voltage response, as computed from the above
      measurements, was low pass and approximated by a cascade of three low pass RC
      filters ("leaky integrators"). These results for cone-->bipolar transmission are
      surprisingly similar to recent results for rod-->bipolar transmission in
      salamander slice preparations. These and other findings suggest that the rate of
      vesicle replenishment rather than the rate of release may be a common factor
      shaping synaptic signal transmission from rods and cones to bipolar cells.

PMID- 18093366
TI  - Temporal resolution and temporal transfer properties: gabaergic and cholinergic
      mechanisms.
AB  - Temporal resolution is a basic property of the visual system and critically
      depends upon retinal temporal coding properties which are also of importance for
      directional coding. Whether the temporal coding properties for directional coding
      derive form inherent properties or critically depend upon the temporal coding
      mechanisms is unclear. Here, the influence of acetylcholine and GABA upon
      photopic temporal coding was investigated in goldfish, using flicker stimuli, in
      a behavioral and an electrophysiological (ERG) approach. The goldfish temporal
      resolution ability decreased from more than 90% correct choices at 20 Hz flicker
      frequency to about 65% at 45 Hz flicker frequency with a flicker fusion frequency
      of approximately 39 Hz. Blockade of GABAa-receptors reduced the flicker fusion
      frequency to about 23 Hz, not affecting temporal resolution below 20 Hz flicker
      frequency. Partial blockade of nicotinic acetylcholine receptors reduced the
      flicker fusion frequency slightly and lowered the temporal resolution ability in
      the 25-30 Hz range. Blockade of muscarinic acetylcholine receptors had a smaller
      effect than the partial blockade of nicotinic acetylcholine receptors. In ERG
      recordings, blocking GABAa-receptors increased the a- and b-wave amplitude,
      induced a delay, an increase and a slow fall-off of the d-wave. Blocking GABAc
      receptors had little effect. Blocking GABAa- or GABAa/c-receptors changed the
      temporal resolution, when expressed as a linear filter, from a 3rd degree filter
      with resonance to a low order low-pass filter with a low upper limit frequency.
      The temporal transfer properties were barely changed by blocking either nicotinic
      or muscarinic acetylcholine receptors, although ERG-components increased in
      amplitude to varying degrees. The behavioral and electrophysiological data
      indicate the important role of GABA for temporal processing but little
      involvement of the cholinergic system. It is proposed that the interaction of the
      GABAergic amacrine cell network and bipolar cells determines the gain of the
      retinal temporal coding in the upper frequency range.

PMID- 18093367
TI  - No age-related cell loss in three retinal nuclear layers of the Long-Evans rat.
AB  - The retina mainly contains ganglion, bipolar and photoreceptor cells which are
      distributed in the ganglion cell layer (GCL), inner nuclear layer (INL) and outer
      nuclear layer (ONL), respectively. Whether there is an age-related loss of these
      retinal cells remains not well understood. Cell density and the total number of
      cells were two commonly used measures to evaluate such age-related changes in
      most previous studies and provided controversial conclusions. The use of density
      measures as decisive data is problematic because the total area of the retina was
      expanded in aging, whereas the application of the total number of cells was
      limited for assessing ganglion cells. In this study, thus, we wanted to test
      whether there is an age-related cell loss in the GCL, INL and ONL and if so,
      whether such a loss is correlated to the convergence ratio of these cells. We
      used stereological procedures to quantify the total number of cells in the three
      retinal nuclear layers in six young and six aged Long-Evans rats. We found that
      during aging, the total volume of the retina remained unchanged, but the retina
      became thinner. There was no cell loss in each individual nuclear layer, and the
      ratio of the ONL to INL to GCL was preserved.

PMID- 18093368
TI  - The multifocal pattern electroretinogram (mfPERG) and cone-isolating stimuli.
AB  - The number of L cones in the retina normally exceeds that of the M cones. Because
      normal color vision does not depend on the ratio of L- and M-photoreceptors,
      their signals must undergo an alteration in gain before being analyzed in the
      cortex. Previous studies have shown that this gain must take place before the
      cortex, but after the bipolar/amacrine cell layer of the retina. The aim of this
      study was to obtain topographical information about L- and M-cone activity at the
      ganglion cell layer using multifocal pattern electroretinography (mfPERG). A
      standard (black and white) stimulus was used, as well as stimuli modulating only
      the long wavelength-sensitive (L) or only the middle wavelength-sensitive (M)
      cones. The L:M ratio was calculated from the amplitude of the L-cone isolating
      mfPERG to that of the M-cone isolating mfPERG of 10 trichromats. Both the
      positive and negative components of the waveform were analyzed. Additional
      recordings of single cone modulated mfERGs were obtained from nine of the 10
      subjects. We also recorded from one protanope and one deuteranope. The L:M cone
      amplitude ratios for both deflections of the mfPERG in the trichromats were
      around unity (medians 1.18 and 1.16, respectively) for the central 8 degrees of
      retina. In the peripheral retina between 12.8 degrees and 26 degrees , this ratio
      increased to 1.42 for the positive component, and 1.37 for the negative
      component. The median L:M cone amplitude ratios for the mfPERG were higher and
      ranged between 1.00-2.78 in the central 8 degrees and 1.29-2.78 in the periphery.
      The results indicate that a major gain adjustment of the retinal signals takes
      place at the ganglion cell level, and that the ratio is higher at eccentric
      locations than in the central retinal area.

PMID- 18093369
TI  - Split of attentional resources in human visual cortex.
AB  - Visual spatial attention has been described as a process that favors the
      processing of sensory information that falls into the "spotlight of attention."
      Recent studies have provided support for an ability to split this attentional
      focus to selectively process spatially separate locations. Using functional
      magnetic resonance imaging, the signature for the presence of multiple spotlights
      is the presence of multiple retinotopically specific foci of activation in
      striate and extrastriate visual areas. We used this approach to investigate the
      presence of such separable activations as a function of the eccentricity of the
      spatial foci of attention. Visual stimuli consisted of letters and digits
      displayed in rapid serial visual presentation (RSVP). Five RSVP streams were
      presented simultaneously, one in the center of the visual field and one in each
      visual field quadrant. Subjects had to deploy their attention either to a single
      peripheral location or two non-contiguous regions performing a match-mismatch
      judgment. The results show that dividing attention leads to multiple spotlights
      of attention for central as well as more peripheral locations of the visual
      field. However, depending on the exact location and width of the attentional
      spotlights, resulting activation maps might reveal merged activation patterns
      even in the presence of distinct attentional spotlights.

PMID- 18093370
TI  - Properties of stimulus-dependent synchrony in retinal ganglion cells.
AB  - Neighboring retinal ganglion cells often spike synchronously, but the possible
      function and mechanism of this synchrony is unclear. Recently, the strength of
      the fast correlation between ON-OFF directionally selective cells of the rabbit
      retina was shown to be stimulus dependent. Here, we extend that study,
      investigating stimulus-dependent correlation among multiple ganglion-cell
      classes, using multi-electrode recordings. Our results generalized those for
      directionally selective cells. All cell pairs exhibiting significant spike
      synchrony did it for an extended edge but rarely for full-field stimuli. The
      strength of this synchrony did not depend on the amplitude of the response and
      correlations could be present even when the cells' receptive fields did not
      overlap. In addition, correlations tended to be orientation selective in a manner
      predictable by the relative positions of the receptive fields. Finally, extended
      edges and full-field stimuli produced significantly greater and smaller
      correlations than predicted by chance respectively. We propose an amacrine
      network model for the enhancement and depression of correlation. Such an
      apparently purposeful control of correlation adds evidence for retinal synchrony
      playing a functional role in vision.

PMID- 18093371
TI  - Development of cortical responses to optic flow.
AB  - Humans discriminate approaching objects from receding ones shortly after birth,
      and optic flow associated with self-motion may activate distinctive brain
      networks, including the human MT+ complex. We sought evidence for evoked brain
      activity that distinguished radial motion from other optic flow patterns, such as
      translation or rotation by recording steady-state visual evoked potentials
      (ssVEPs), in both adults and 4-6 month-old infants to direction-reversing optic
      flow patterns. In adults, radial flow evoked distinctive brain responses in both
      the time and frequency domains. Differences between expansion/contraction and
      both translation and rotation were especially strong in lateral channels (PO7 and
      PO8), and there was an asymmetry between responses to expansion and contraction.
      In contrast, infants' evoked response waveforms to all flow types were
      equivalent, and showed no evidence of the expansion/contraction asymmetry.
      Infants' responses were largest and most reliable for the translation patterns in
      which all dots moved in the same direction. This pattern of response is
      consistent with an account in which motion processing systems detecting locally
      uniform motion develop earlier than do systems specializing in complex, globally
      non-uniform patterns of motion, and with evidence suggesting that motion
      processing undergoes prolonged postnatal development.

PMID- 18093372
TI  - First order connections of the visual sector of the thalamic reticular nucleus in
      marmoset monkeys (Callithrix jacchus).
AB  - The thalamic reticular nucleus (TRN) supplies an important inhibitory input to
      the dorsal thalamus. Previous studies in non-primate mammals have suggested that
      the visual sector of the TRN has a lateral division, which has connections with
      first-order (primary) sensory thalamic and cortical areas, and a medial division,
      which has connections with higher-order (association) thalamic and cortical
      areas. However, the question whether the primate TRN is segregated in the same
      manner is controversial. Here, we investigated the connections of the TRN in a
      New World primate, the marmoset (Callithrix jacchus). The topography of labeled
      cells and terminals was analyzed following iontophoretic injections of tracers
      into the primary visual cortex (V1) or the dorsal lateral geniculate nucleus
      (LGNd). The results show that rostroventral TRN, adjacent to the LGNd, is
      primarily connected with primary visual areas, while the most caudal parts of the
      TRN are associated with higher order visual thalamic areas. A small region of the
      TRN near the caudal pole of the LGNd (foveal representation) contains connections
      where first (lateral TRN) and higher order visual areas (medial TRN) overlap.
      Reciprocal connections between LGNd and TRN are topographically organized, so
      that a series of rostrocaudal injections within the LGNd labeled cells and
      terminals in the TRN in a pattern shaped like rostrocaudal overlapping "fish
      scales." We propose that the dorsal areas of the TRN, adjacent to the top of the
      LGNd, represent the lower visual field (connected with medial LGNd), and the more
      ventral parts of the TRN contain a map representing the upper visual field
      (connected with lateral LGNd).

PMID- 18093407
TI  - Introduction: The pharmacological profile of eprosartan--implications for
      cerebrovascular and cardiovascular risk reduction.
AB  - Moderate elevations in blood pressure translate to significant increases in
      cardiovascular and cerebro vascular risk. Beneficially, this relationship allows
      small decreases in blood pressure to be associated with risk reduction. Both the
      renin-angiotensin system and the sympathetic nervous system are involved in
      hypertension, hence targeting these systems is likely to be of benefit in the
      treatment of hypertension. Angiotensin II type 1 receptor blockers (ARBs) are
      used for controlling blood pressure and treating heart failure in a broad range
      of patients, including those with diabetes and the elderly. Not only have ARBs
      shown good efficacy and tolerability, they also appear to have a protective
      effect that goes beyond that expected from the reduction of blood pressure. The
      ARB eprosartan is a nonbiphenyl nontetrazole angiotensin II type 1 receptor (AT1)
      antagonist, which acts to decrease total peripheral resistance. Eprosartan acts
      at vascular AT1 receptors (postsynaptically) and at presynaptic AT1 receptors,
      where it inhibits noradrenaline release. In clinical studies, eprosartan has been
      shown to significantly reduce cardiovascular and cerebrovascular events, whilst
      avoiding the persistent cough that commonly occurs with the use of angiotensin
      converting enzyme inhibitors. Eprosartan can also be differentiated from other
      ARBs due to its noradrenergic effects, which other ARBs used at therapeutic doses
      do not possess. Eprosartan, therefore, represents a useful therapeutic option in
      the management of patients with hypertension, including those with a history of
      stroke or with co-morbid type 2 diabetes mellitus.

PMID- 18093408
TI  - Angiotensin blockade with eprosartan: vascular and functional implications.
AB  - It is clear that the renin-angiotensin system (RAS) and the sympathetic nervous
      system (SNS) play key roles in sustaining elevated blood pressure, subsequently
      resulting in increased risks of cardiovascular (CV), cerebrovascular and kidney
      disease. Modifying these systems with antihypertensive agents has led to the
      discovery that their effects may indeed extend beyond controlling blood pressure.
      Within blood vessels, angiotensin II type 1 receptor blockers (ARBs) inhibit
      postsynaptic angiotensin II type 1 receptors (AT1). The ARB eprosartan, in
      contrast to other ARBs, also inhibits prejunctional AT1 receptors, which regulate
      noradrenaline release. The positive effects of eprosartan on blood pressure have
      been studied extensively, and are due to modulation of both the RAS and the SNS
      (through stimulation of the angiotensin II type 2 [AT2] receptor). Of importance
      to isolated systolic hypertension, trough sitting systolic blood pressure (SBP)
      is also significantly reduced with eprosartan. In addition, many studies have
      shown how the benefits of eprosartan go beyond that of blood pressure control
      alone. Eprosartan has shown positive effects on vascular inflammation and
      resistance to oxidation and/or modification of low-density lipoprotein. A wealth
      of other positive actions are associated with eprosartan treatment, including
      effects on platelet aggregation, kidney function and structure, progressive left
      ventricular dysfunction and central SBP. Clinical studies have clearly
      demonstrated the benefits of RAS blockade alongside the additional effects beyond
      blood pressure control with eprosartan treatment. These data place eprosartan as
      an effective agent to prevent CV, cerebrovascular and renal complications
      associated with high blood pressure.

PMID- 18093409
TI  - Observational Study on Cognitive function And systolic blood pressure Reduction
      (OSCAR): preliminary analysis of 6-month data from > 10,000 patients and review
      of the literature.
AB  - Given the ageing population, dementia is an ever-increasing health burden. A
      positive correlation between cognitive decline or dementia and blood pressure
      levels has been indicated. There is, however, conflicting evidence over the
      definitive link between the use of antihypertensives and the subsequent reduction
      of cognitive decline. The specific use of angiotensin II receptor blockers (ARBs)
      in preventing vascular dementia has been investigated with eprosartan treatment.
      In animal studies utilising stroke-prone rats, eprosartan has been shown to
      reduce end-organ damage of the heart and kidneys in a study assessing
      cardiomyopathy and renal failure. The Morbidity and mortality after Stroke,
      Eprosartan compared with nitrendipine for Secondary prevention (MOSES) study,
      assessing 1405 patients, has shown the cerebroprotective effects of eprosartan
      compared with the calcium channel blocker nitrendipine. In this study, however,
      no change in cognitive function, as assessed by the mini-mental status
      examination (MMSE) score, was seen between the treatment groups. The
      Observational Study on Cognitive function And systolic blood pressure Reduction
      (OSCAR) trial, including more than 60,000 hypertensive patients, also assessed
      the ability of eprosartan to alter the MMSE score. In contrast to the MOSES
      trial, preliminary data from 10,000 patients after 6 months of treatment
      identified a decrease in blood pressure alongside a significant increase in MMSE
      score. Specific subpopulations within this study, including the elderly, patients
      with higher initial systolic blood pressure and patients with a body mass index
      (BMI) of 25-30 kg/m2 showed the greatest change in MMSE score. These data
      indicate an association with blood pressure reduction and improvement of
      cognitive function with eprosartan treatment.

PMID- 18093410
TI  - The SCORE model in the POWER study: an attempt to focus the limited resources for
      prevention on patients with greatest need.
AB  - As the emergence of cardiovascular disease (CVD) is linked to modifiable
      lifestyle and physiological factors, it is increasingly important to concentrate
      on preventative strategies. For preventative measures to be beneficial it is
      necessary to clearly identify patients at risk--given that multiple risk factors
      often cluster this requires the assessment of total cardiovascular (CV) risk.
      Total CV risk can be estimated in different ways; in the guidelines on the
      management of arterial hypertension by a Joint Task Force of the European Society
      of Hypertension and the European Society of Cardiology a categorical approach was
      recommended. A model based on results from the US Framingham study has been
      available for many years. Systemic COronary Risk Evaluation (SCORE) is a recently
      developed total CV risk assessment model, based on approximately 3 million person
      years of observation, which estimates fatal CVD events over a 10-year period,
      incorporating both coronary heart disease and cerebrovascular disease. The SCORE
      model aids clinicians in their decision on how to engage in preventative measures
      and how to adjust the intensity of their preventative efforts in accordance with
      the total CV risk of the patient. The SCORE model has been incorporated into the
      Physicians Observational Work on Patient Education According to their Vascular
      Risk (POWER) study. This study, with an estimated sample size of 60,000 patients,
      will determine if SCORE can act as a suitable tool to aid the lowering of CV
      risk.

PMID- 18093411
TI  - Risk reduction by preventing stroke: need for blockade of angiotensin II and
      catecholamines?
AB  - Angiotensin (AT) II and noradrenaline play major roles in hypertension, stroke
      and coronary heart disease, which are themselves interlinked. Harmful effects of
      AT II are not blocked solely by angiotensin-converting enzyme inhibitors, as it
      is now evident that AT II is generated by other enzymes such as chymase.
      Angiotensin II also stimulates noradrenaline release modulated by presynaptic
      receptors on sympathetic nerves. Numerous studies have defined the action of the
      AT II type 1 receptor blocker (ARB) eprosartan as controlling noradrenergic and
      adrenergic effects, resulting from actions on the renin-angiotensin-aldosterone
      system and the sympathetic nervous system. Clinical studies have been carried out
      to assess the effects of ARBs on morbidity and mortality. The Valsartan
      Antihypertensive Long-term Use Evaluation (VALUE) trial compared the effects of
      valsartan and the calcium channel blocker (CCB) amlodipine in over 15,000
      patients at high risk of a cardiac event. Results showed that blood pressure was
      reduced by both treatments and cardiac mortality/morbidity was similar in both
      groups. By contrast, the Morbidity and mortality after Stroke, Eprosartan
      compared with nitrendipine for Secondary prevention (MOSES) study (n = 1405)
      generated results which differed from the VALUE study, in that blood pressure was
      reduced by both eprosartan and nitrendipine, but eprosartan reduced all
      cardiovascular and cerebrovascular events to a greater extent than nitrendipine.
      It is also possible that any delayed clinical benefit of eprosartan could be due
      to reverse cardiac remodelling. Eprosartan, by blocking AT II receptors, reducing
      noradrenaline release and blocking catecholamine actions, may, therefore, provide
      greater protection against vascular events than CCBs or other ARBs.

PMID- 18093412
TI  - Results of stability studies with doping agents in urine.
AB  - For a correct interpretation of analytical results in doping control, knowledge
      on the stability of prohibited substances in the urinary matrix is a
      prerequisite. So far, limited data is available on the stability of prohibited
      substances in unaltered urine because most of the studies investigating the
      stability of drugs have used stabilized, sterilized, or filtered urine. In this
      work, the long-term stability of ephedrine, methylephedrine, cathine, 19
      norandrosterone glucuronide, and a wide range of diuretics was determined over a
      period of 9 months at -20 degrees C, 4 degrees C, 22 degrees C, and 37 degrees C.
      Short-term stability, including the influence of 6 freeze-thaw cycles and 15 h
      storage at 60 degrees C, was also investigated. Often, a tolerance limit of 15%,
      similar to what is commonly used in the evaluation of precision data during
      method validation, is used to evaluate stability. This paper describes an
      alternative approach, using measurement uncertainty data to evaluate long-term
      stability with a probability of 95%, and proposes a simple alternative for
      investigating the stability for non-threshold substances. The results indicate
      that all the investigated substances are stable (alpha=0.05) when stored at -20
      degrees C and 4 degrees C, but that at higher temperatures significant
      degradation effects can occur. The study also shows that degradation can be
      dependent on the urinary matrix and that the results from stability studies using
      stabilized, filtered, or sterilized urine can underestimate degradation effects.

PMID- 18093413
TI  - Intensity of the internal standard response as the basis for reporting a test
      specimen as negative or inconclusive.
AB  - Under normal circumstances, a test specimen is reported as "negative" when the
      response of the analyte is absent. However, if the intensity of the internal
      standard (IS) is low, indicating interference factors, the test could be
      considered "inconclusive." A quantitative hypothesis, A=(R x I x S)/L, serves as
      the "cutoff" for the acceptable signal-to-noise (S/N) ratio for the IS in making
      "negative/inconclusive" decisions, where A is the acceptable S/N ratio for
      internal standard; R is the relative response of the IS and the analyte (same
      concentration); I is the concentration of the IS; S is the (minimal S/N ratio);
      and L is the limit of detection. The hypothesis was empirically tested using the
      9-carboxy-11-nor-Delta(9)-tetrahydrocannabinol (THC-COOH) analyte, THC-COOH-d(3)
      IS, with ibuprofen and hydrogen peroxide (H2O2) as interference factors. Urine
      specimens containing 0-5 ng/mL of THC-COOH were spiked with various quantities of
      ibuprofen or H(2)O(2), followed by liquid-liquid extraction, derivatization, and
      gas chromatography-mass spectrometry (GC-MS) analysis under selected-ion
      monitoring mode. Among the "adulterated" test specimens evaluated (those with an
      S/N for the internal standard below the acceptable IS S/N "A") the quantitative
      criterion was indeed found to provide a useful guide for making
      negative/inconclusive decisions. This equation could be programmed into the
      instrument software to flag results as being inconclusive when they do not meet
      the criteria described in this paper.

PMID- 18093415
TI  - Gamma-hydroxybutyrate concentrations in the blood of impaired drivers, users of
      illicit drugs, and medical examiner cases.
AB  - Gamma-hydroxybutyrate (GHB) was determined in blood samples from impaired
      drivers, people arrested for petty drug offenses (non-traffic cases), and GHB
      related deaths. The method of analysis involved conversion of GHB into gamma
      butyrolactone and determination of the latter by gas chromatography with a flame
      ionization detector, and with gamma-valerolactone as the internal standard. The
      mean and median concentrations of GHB in blood from impaired drivers (N=473) were
      90 and 84 mg/L, respectively, and offenders were predominantly men (96%) with an
      average age of 26 year (range 15-50 year). In 185 cases, GHB was the only drug
      present in blood at mean and median concentrations of 92 and 86 mg/L,
      respectively. People arrested for petty drug offenses (N=1061) had slightly
      higher GHB concentrations in their blood: median 118 mg/L for men and 111 mg/L
      for women. In GHB-related deaths (N=33), the mean and median concentrations were
      considerably higher: 307 mg/L and 190 mg/L, respectively, and the highest was
      2200 mg/L. The typical signs of drug influence noted by the arresting police
      officers included sedation, agitation, slurred speech, irrational behaviour,
      jerky movements, and spitting. The short elimination half-life of GHB means that
      the concentrations in blood decrease rapidly and are probably a lot lower than at
      the time of driving, which was 30-90 min earlier.

PMID- 18093414
TI  - Gabapentin in horses: validation of an analytical method for gabapentin
      quantitation.
AB  - Gabapentin [1-(aminomethyl)cyclohexaneacetic acid, Neurontin], is a new
      anticonvulsant used as adjunctive therapy in the treatment of partial seizures in
      humans not controlled with standard antiseizure drugs, and it has also been used
      in veterinary medicine. In performance horses, gabapentin is listed as a class 3
      performance-enhancing substance by the Association of Racing Commissioners
      International, and thus is considered to have the potential to influence the
      outcome of races. Therefore, we developed and validated a sensitive gas
      chromatographic-mass spectrometric (GC-MS) method for gabapentin detection. Gamma
      aminobutyric acid-d(2) (GABA-d(2)) was used as an internal standard during solid
      phase extraction; lacking the cyclohexyl ring of gabapentin, GABA-d(2) formed a
      lactam structure to only a minor extent. Gabapentin, on the other hand, readily
      formed a lactam on thermal exposure during trimethylsilyl-derivatization and/or
      GC analysis; electrospray-ionization MS was employed to verify that the original
      compound was present as the expected 171 m.w. compound. Extraction efficiency for
      the assay was about 60%, and a curvilinear standard curve ranging from 50 ng/mL
      to 3000 ng/mL provided excellent within-run and between-run coefficients of
      variation and accuracies over a range of low, medium, and high values. The limit
      of detection, defined as the concentration calculated from the mean response at
      zero concentration plus two times the standard deviation, was calculated at 7.6
      ng/mL; the limit of quantitation, defined as the concentration calculated from
      the mean of the zero responses plus five times the standard deviation, was
      calculated at 17 ng/mL. This method will enable accurate quantification of
      gabapentin in equine biological fluids for use in both pharmacokinetic and
      forensic studies.

PMID- 18093416
TI  - Determination of illicit drugs and their metabolites in human urine by liquid
      chromatography tandem mass spectrometry including relative ion intensity
      criterion.
AB  - A method, using 0.5 mL of urine, was developed for the simultaneous determination
      of ecgonine methyl ester, benzoylecgonine, morphine, codeine, 6-acetylmorphine,
      amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4
      methylenedioxymethamphetamine (MDMA), methadone, 2-ethylidene-1,5-dimethyl-3,3
      diphenylpyrrolidine (EDDP), and d-lysergic acid diethylamide (LSD). The analysis
      was performed by liquid chromatography with tandem mass spectrometry, after solid
      phase extraction in the presence of their deuterated analogues. Reversed-phase
      separation on an Atlantis dC18 column was achieved in 12.5 min, under gradient
      conditions. The method was fully validated, including linearity (1-2000 microg/L
      for ecgonine methyl ester, benzoylecgonine, 6-acetylmorphine, methamphetamine,
      MDMA, and EDDP; 2-2000 microg/L for morphine, codeine, MDA, and methadone; 2-1000
      microg/L for amphetamine, and 0.2-100 microg/L for LSD; r(2)>0.99); recovery
      (>65%), within-day and between-day precision, and accuracy (CV and MRE<15%);
      limit of detection (0.1 microg/L for LSD, 0.5 microg/L for ecgonine methyl ester,
      benzoylecgonine, methamphetamine, MDMA, 6-monoacetylmorphine, and EDDP, and 1
      microg/L for amphetamine, MDA, morphine, and methadone); quantitation (lowest
      level of the calibration curve); relative ion intensities, freeze-and-thaw
      stability, and matrix effect. The procedure showed to be sensitive and specific,
      and was applied to real cases and quality control samples from a quality control
      program.

PMID- 18093417
TI  - Comparison of drug concentrations in postmortem cerebrospinal fluid and blood
      specimens.
AB  - The concentration of drugs and metabolites in cerebrospinal fluid (CSF) and blood
      were determined in 282 autopsied cases using liquid-liquid extraction techniques
      and gas chromatographic analyses. All drugs were confirmed in one matrix by gas
      chromatography-mass spectrometry. CSF/blood ratios were used to compare the two
      biological fluids. Classes of drugs evaluated in this study included:
      benzodiazepines, anticonvulsants, sedatives, opioids, antidepressants,
      anesthetics, and antihistamines. The majority of the drugs tested were readily
      detected in CSF specimens. The average CSF/blood ratio for most drugs was in the
      range of 0.05-0.50. Interpretation of these results is difficult because protein
      binding, half-life, hydrophobic properties, and pKa of a drug, in addition to
      survival time after drug use, influence the CSF/blood ratio. While CSF specimens
      do provide a viable alternative testing matrix when blood specimens are not
      available, they should not be used to estimate blood drug concentrations.

PMID- 18093418
TI  - Detection of methylphenidate in the hair of children treated with Ritalin.
AB  - Hair samples were collected from 17 children (7-16 years of age) who had received
      methylphenidate therapy on a long-term basis. The dose was 10-60 mg per day. To
      20 mg of pulverized hair, phosphate buffer and internal standard (norpethidine)
      were added. Extraction was performed by ultrasonic treatment, followed by
      isolation by alkaline extraction with isohexane. Derivatization with N-Methyl
      bisheptafluorobutyric amide enabled gas chromatography-mass spectrometry analysis
      of the perfluorobutyryl derivatives in selected ion monitoring mode. The
      methylphenidate concentrations lay between 0.073 and 1.1 ng/mg hair. It was noted
      that at higher daily doses there was a tendency toward increased concentrations
      in the hair, but for testing of compliance, the incorporation into hair did not
      occur with the required high correlation between daily dose and concentration in
      the hair.

PMID- 18093419
TI  - Clarification of ethanol-positive case using urine serotonin metabolite ratio.
AB  - This paper intends to provide investigators with information useful in
      determining the presence of postmortem ethanol in fatal accidents and a case
      history of an accident that involved postmortem alcohol formation is presented.
      An ethanol-positive fatal case initially reported as being from ingestion was
      ultimately determined to be from postmortem ethanol production using the ratio of
      two serotonin metabolites found in urine. This case involved a transportation
      accident that could have resulted in additional hardships for the victim's family
      through loss of compensation and reputation.

PMID- 18093420
TI  - Determination of benzodiazepines in oral fluid using LC-MS-MS.
AB  - A rapid, simple, highly sensitive procedure for the simultaneous analysis of
      bromazepam, alprazolam, clonazepam, lorazepam, oxazepam, diazepam, midazolam,
      flurazepam, flunitrazepam, nordiazepam, triazolam, temazepam, nitrazepam, and
      chlordiazepoxide in oral fluid is described, using liquid chromatography coupled
      to a triple quadrupole mass spectrometer in positive electrospray mode.
      Benzodiazepines in oral fluid samples (1 mL) were analyzed using the Quantisal
      collection device, quantified using solid-phase extraction, and detected using
      liquid chromatography with tandem mass spectrometric detection. For confirmation,
      two transitions were monitored and one ion ratio determined, which was within 20%
      of the ratio for known calibration standards. The limits of quantitation ranged
      from 0.5-5 ng/mL of neat oral fluid; the intraday precision of the assays (n=5)
      ranged from 2.8-7.29%; and the interday precision ranged from 1.42-6.8% (n=5).
      The percentage recovery of the drugs from the collection pads ranged from a low
      of 81.4% for midazolam to the highest of 90.17% for nitrazepam. The procedure can
      be applied to authentic oral fluid specimens.

PMID- 18093421
TI  - Detection of bumetanide in an over-the-counter dietary supplement.
AB  - Bumetanide is a loop diuretic used clinically to treat heart failure, acute renal
      failure, high blood pressure, and edema. However, diuretics may also be used by
      athletes as masking agents and to decrease weight. Taken as masking agents,
      diuretics increase urine production and decrease urinary concentrations of banned
      performance-enhancing agents, such as anabolic steroids. StarCaps is an over-the
      counter dietary supplement marketed as a diet aid. The manufacturer claims that
      the product contains only natural cleansing agents and emphasizes that it is free
      from traditional appetite suppressants such as sympathomimetic amines. However,
      no such disclaimer is made concerning diuretic agents. A single StarCaps capsule
      was administered to two male and two female volunteers, and their urine specimens
      were collected at discrete intervals (2, 4, 8, and 12 h) post administration. The
      specimens were analyzed by a high-performance liquid chromatography-mass
      spectrometry quadrupole (HPLC-MS) method, and bumetanide was detected in all
      specimens (4.6 to 351.3 ng/mL). Adjusting the bumetanide concentrations for
      creatinine content did little to normalize the excretion profiles. Bumetanide was
      also detected in the StarCaps capsules at concentrations approaching therapeutic
      doses. HPLC-quadrupole-time-of-flight mass spectrometry was used to confirm the
      presence of bumetanide in the urine samples and StarCaps capsules. The results
      showed that unregulated dietary supplements may put consumers at risk for
      unwitting consumption of prescription medications, and that it is possible for
      athletes to inadvertently test positive for bumetanide and face disciplinary
      actions.

PMID- 18093422
TI  - [Effects of endothelial lipase on mRNA expression of adhesion molecule of human
      umbilical vascular endothelial cells].
AB  - OBJECTIVE: To explore the relationship between human umbilical vascular
      endothelial cells (HUVECs) and endothelial lipase (EL), and the effect of EL on
      expression of endothelial cell adhesion molecule (ICAM). METHODS: HUVECs was
      treated with tumor necrosis factor-alpha(TNF-alpha) 10 microg/L and the mRNA of
      adhesion molecules [intercellular adhesion molecule-1 (ICAM-1), vascular cellular
      adhesion molecule-1 (VCAM-1) and E-selectin] were detected by reverse
      transcription-polymerase chain reaction (RT-PCR). Then the effect of 50 microg/L
      anti-endothelial lipase (anti-EL) antibody on the influence of TNF-alpha on these
      adhesion molecules was observed. RESULTS: After being treated with TNF-alpha, the
      mRNA of adhesion molecules expressed by HUVECs were significant up-regulated,
      there was significant difference compared with control group (all P<0.01). These
      effects of TNF-alpha were significantly abolished by 50 microg/L anti-EL antibody
      (P<0.05 or P<0.01). CONCLUSION: EL can affect the expression of adhesion
      molecules on endothelial cell adhesion molecule. This effect of EL may play a
      role in the pathophysiologic process in the pathogenesis progress of
      atherosclerosis.

PMID- 18093423
TI  - [Screening for cellular signal transduction pathway involved in C-reactive
      protein induced endothelial cell inflammation].
AB  - OBJECTIVE: To investigate the cellular signal transduction pathway involved in
      participation of C-reactive protein (CRP) in inflammation process in endothelial
      cell. METHODS: Human umbilical vascular endothelial cells were cultured and
      characterized by anti-Factor VIII-related antigen. The cells were divided into
      CRP group and control group, and they were respectively treated with CRP (20
      mg/L) or serum-free medium for 24 hours. RNAs of two groups were extracted and
      analyzed by human signal transduction pathway gene array. RESULTS: Expressions of
      13 genes were increased, whereas expressions of 25 genes were decreased in CRP
      group compared with control group. Especially, WNT1 inducible signaling pathway
      protein 2 (WISP2) was increased by 37.63 folds, which was believed to involve in
      inflammation process as a growth factor, p53 was increased by 30.50 folds, which
      was a key factor to modulate apoptosis, whereas, Bcl-x and Bcl-2 were decreased
      by 9.61% and 49.95% which were characterized as an important factor to prevent
      apoptosis. Vascular cell adhesion molecule-1 (VCAM-1) was increased by 2.75 folds
      after treated with CRP, while intercellular adhesion molecular (ICAM) between two
      groups didn't show statistically significant difference. CONCLUSION: CRP may be
      involved in inflammatory process of endothelial cell, and the mechanism may be to
      induce apoptosis and activate cellular signal transduction pathway of cell
      adhesion proteins.

PMID- 18093424
TI  - [Expression of angiotensin converting enzyme and angiotensin II receptor in
      rabbits with hyperthyroid cardiomyopathy].
AB  - OBJECTIVE: To explore the pathogenesis of hyperthyroid cardiomyopathy. METHODS: A
      rabbit model of hyperthyroid cardiomyopathy was reproduced by daily
      intraperitoneal injection of L-thyroxine (L-Thy, 45 microg x kg(-1)xd(-1)) for 28
      consecutive days. Forty New Zealand rabbits were randomly divided into four
      groups: control group, L-Thy group, imidapril group, and valsartan group.
      Ventricular tissues were harvested after 4 weeks. Cardiac hypertrophy index and
      cardiomyocyte diameter were assessed. Cardiac fibrosis was shown by Masson's
      stain and collagen volume fraction (CVF) was measured using pathological image
      analytic system. Plasma and cardiac angiotensin II (AngII) concentration were
      measured with radioimmunoassay (RIAs). mRNA expression of angiotensin converting
      enzyme(ACE), one tape angiotensin recipient-II(AT1R) and AT2R were semi
      quantified with reverse transcription-polymerase chain reaction (RT-PCR).
      Expression of ACE, AT1R and AT2R protein were evaluated with Western blotting
      analysis. RESULTS: Compared with control group, rabbits treated with L-Thy only
      were found to have remarkable myocardial hypertrophy and extracellular matrix
      fibrosis. Increased plasma and tissue AngII were detected in L-Thy group. RT-PCR
      and Western blotting analysis revealed enhanced mRNA and protein expression of
      ACE, AT1R and AT2R. It was also demonstrated that both imidapril and valsartan
      alleviated cardiac hypertrophy and extracellular matrix fibrosis induced by L
      Thy. Compared with L-Thy and valsartan group, imidapril group showed
      significantly lower plasma /tissue AngII concentration and more effective
      inhibition of extracellular matrix fibrosis. Imidapril did not alter the
      expression of ACE, AT1R or AT2R. Plasma concentration of AngII was markedly
      higher in valsartan group compared with L-Thy group, whereas tissue AngII
      concentration showed no significant difference between two groups. In valsartan
      group, AT1R and AT2R mRNA expressions were significantly upregulated, whereas
      valsartan did not change mRNA and protein expression of ACE. CONCLUSION: Renin
      angiotensin system (RAS) may play an important role in hyperthyroid
      cardiomyopathy. Imidapril and valsartan may exert beneficial effects on
      hyperthyroid cardiomyopathy via retarding myocardial remodeling.

PMID- 18093425
TI  - [B mode blood flow imaging in the diagnosis of diseases of lower extremities in
      diabetic patients].

PMID- 18093426
TI  - [Effects of propofol on the changes in cytoskeleton and cellular permeability of
      human umbilical vascular endothelial cells monolayer induced by
      lipopolysaccharide].
AB  - OBJECTIVE: To investigate the effects of propofol on the changes in actin
      cytoskeleton and permeability of cultured human umbilical vascular endothelial
      cells (HUVECs) monolayer induced by lipopolysaccharide (LPS). METHODS: HUVECs
      were randomly assigned to one of the following seven groups: no additives
      (negative control), LPS alone (1 mg/L and 10 mg/L), propofol alone (4 mg/L),
      introlipid alone, LPS (10 mg/L ) combination with propofol (4 mg/L) and LPS (10
      mg/L ) together with introlipid (4 mg/L). Changes in filtration coefficients (Kf)
      and osmotic reflection coefficients (sigma) were measured, and changes in
      filamentous actin (F-actin) measured by F-actin fluorometry, and expression of
      nitrotyrosine analyzed by immunocytochemistry were observed in cultured HUVECs.
      RESULTS: Compared with the control group, the LPS alone group Kf values were
      significantly increased and the sigma values decreased,the F-actin content was
      decreased and the expression of nitrotyrosine was increased (all P<0.01),
      especially in the high dose LPS alone group. The co-treatment of propofol and LPS
      significantly reduced levels of LPS-enhanced nitrotyrosine protein, and
      significantly attenuated the changes in Kf and sigma values (all P<0.01), while
      introlipid group had no such beneficial effects. CONCLUSION: Propofol rather than
      introlipid, significantly inhibit LPS-induced increase in permeability of HUVECs
      and alterations in F-actin organization. The scavenging actions of propofol on
      peroxynitrite may be helpful to attenuate endothelial barrier dysfunction as
      shown in our current study.

PMID- 18093427
TI  - [Protective effect of melatonin against renal dysfunction following severe burn
      in rats].
AB  - OBJECTIVE: To explore the protective effect of melatonin (MLT) against renal
      dysfunction in the early stage of burn in rats. METHODS: Seventy SD rats were
      randomly assigned to three groups: sham control (n=10), burn control (n=30) and
      MLT group (n=30). The 30% total body surface area (TBSA) full-thickness burn was
      induced by immersing the dorsal skin into boiling water for 30 seconds, while MLT
      (10 mg/kg, i.p.) was given immediately postburn, and the same dose was repeated
      once after 12 hours. The contents of malondialdehyde (MDA) and reduced
      glutathione (GSH) in renal tissue, as well as plasma creatinine (BCr) and urea
      nitrogen (BUN) levels were measured at 6, 24 and 72 hours postburn, while the
      activities of glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO) of renal
      tissue were measured only at 6 hours postburn. RESULTS: MDA content was
      significantly increased and GSH content was decreased in renal tissue after a 30
      % TBSA full-thickness burn at all time points. Plasma BCr and BUN levels were
      elevated within 24 hours postburn. All these changes peaked at 6 hours postburn
      (all P<0.01). Single injection of MLT decreased MDA by 27.8% (P<0.01) but
      increased GSH by 44.4% (P<0.05). It also inhibited the rise in plasma BCr and BUN
      levels (P<0.05 and P<0.01). However, repeated MLT injection did not show
      additional effect on these parameters as single injection of MLT. In addition,
      single dose of MLT also lowered the MPO level by 30.2% (P<0.05), but did not
      improve the GSH-Px activity at 6 hours postburn. CONCLUSION: Severe burn may
      result in obvious oxidative stress (within 72 hours postburn) in the kidney with
      acute renal dysfunction (within 24 hours postburn). Single injection of MLT
      partially counteracted these changes, due to its high free radical scavenging
      capacity as well as its inhibitory effect on neutrophil-mediated tissue injury.

PMID- 18093428
TI  - [Effects of mesenteric lymph duct ligation on apoptosis of renal tubule
      epithelial cells in rats after two-hits].
AB  - OBJECTIVE: To explore the effect of mesenteric lymph duct ligation in preventing
      apoptosis of renal tubule epithelial cells in rats by two-hits including
      hemorrhage and lipopolysaccharide (LPS) challenge. METHODS: Forty-five Wistar
      rats were randomly divided into three groups: the ligation group, the non
      ligation group and sham operation group. The two-hits model was established by
      withdrawing the blood via the right side carotid artery of rats and intragastric
      administration 4 mg/kg LPS 6 hours after hemorrhage, and mesenteric lymph flow
      was blocked by ligating mesenteric lymph duct in ligation group. Twenty-four
      hours after operation, kidney was harvested for pathological examination, and the
      apoptosis cells rate of renal tubule epithelial cells were determined by method
      of terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL),
      the expression of apoptosis-correlating gene bcl-2 and bax protein were
      determined by streptavidin-biotin complex (SABC) immunohistochemical method.
      RESULTS: After two-hits, the apoptosis rate and expression of bax protein of
      renal tubule epithelial cells in non-ligation group were significantly increased,
      and expression of bcl-2 protein was significantly lower as compared with those of
      sham operation group (all P<0.01). But the apoptosis rate and expression of bax
      protein of renal tubule epithelial cells in ligation group were significantly
      lower, and expression of bcl-2 protein was significantly increased as compared
      with non-ligation group (all P<0.01). CONCLUSION: The results demonstrate that
      the ligation of mesenteric lymph duct could ameliorate the apoptosis of renal
      tubule epithelial cells in rats as produced by hemorrhage and LPS, and its
      mechanism might relate to the reduction of the down regulation of gene expression
      of bax protein and enhancement of the expression of bcl-2 protein after ligation
      of mesenteric lymph duct.

PMID- 18093429
TI  - [Comparative study of mannitol-induced acute kidney impairments in patients of
      different ages suffering from subarachnoid hemorrhage].
AB  - OBJECTIVE: To analyze and compare the clinical characteristics of mannitol
      induced acute renal function impairment in treatment of patients of different
      ages suffering from subarachnoid hemorrhage (SAH) for the first time. METHODS:
      This study was a review of 1 361 patients with available hospital records
      admitted to the division of neurology due to SAH from February 1989 to December
      2005. Among them, 94 patients had acute renal function impairment as a result of
      mannitol administration. Of these patients, 35 patients were middle-aged (<60
      years old) and 59 patients of old age (>60 years old). The study included the
      time of appearance of renal function impairment after mannitol medication, its
      prognosis, the administration of nephrotoxic drugs, and the dose and duration of
      mannitol therapy. RESULTS: In old age group, abnormal renal function and urine
      routine appeared in 5 days (median), and 4 days (median) respectively, and acute
      renal failure (ARF) was diagnosed in 5 days, and the incidence rate of ARF was
      20.3% after treatment with mannitol. The respective event appeared 7 days, 11
      days, 9 days and 2.8% (P<0.05 or P<0.01) respectively, in middle-aged group. The
      data indicated the elderly patients had poorer tolerance to mannitol, with
      earlier occurrence of mannitol nephrosis, poorer outcome of kidney impairment and
      worse prognosis. Forty-three patients (72.9%) were treated with katlex (with a
      median of total dosage of 400 mg) in old-aged group, 35 patients (100.0%) were
      treated with katlex (with a median of total dosage of 800 mg) in middle-aged
      group, and there was a significant difference between two groups (P<0.01). The
      data indicated the incidence of mannitol nephrosis was lower in patients treated
      with large dosage of mannitol and katlex. The mortality was 3.4% (2/59 cases) and
      0% (0/35 cases) in old-aged and middle-aged groups respectively (P=0.528).
      CONCLUSION: The elderly patients have higher rate of mannitol-induced impairment
      of renal function after SAH than middle-aged patients. The data emphasize that
      proper combination therapy of mannitol with katlex is an effective measure in
      preventing renal failure.

PMID- 18093430
TI  - [Study on the expressions and roles of renal heat shock protein 72 and Toll-like
      receptor 4 in hepatorenal syndrome in rat].
AB  - OBJECTIVE: To explore the expressions and roles of renal heat shock protein
      72(HSP72) and Toll-like receptor 4(TLR4) during development of hepatorenal
      syndrome in rat. METHODS: Following bile duct ligation (BDL), a biliary cirrhosis
      and hepatorenal syndrome rat model was reproduced. The blood, the renal and
      hepatic tissues of the rats were examined at 1, 2, 4 and 6 weeks (6 rats were
      used in each week) after BDL. Blood was withdrawn from the femoral vein and
      centrifuged. The plasma concentrations of alanine aminotransferase (ALT), total
      bilirubin (TBil), blood urea nitrogen (BUN) and creatinine (Cr) were measured,
      and those of the HSP72 and tumor necrosis factor-alpha (TNF-alpha) were assessed
      with enzyme linked immunosorbent assay (ELISA). After weighing liver and kidney
      and expressions of HSP72 and TLR4 in renal tissue were determined by reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blotting. All data
      were compared with control group (C group). RESULTS: The plasma levels of ALT,
      TBil at each week and of BUN, Cr at 4 and 6 weeks were increased significantly
      (all P<0.05). The concentration of plasma HSP72 and the expressions of renal
      HSP72 mRNA and protein were lower (especially at 4 and 6 weeks, both P<0.01) in
      BDL rats compared with sham operation rats. But the plasma TNF-alpha levels and
      renal TLR4 (mRNA and protein) expressions were significantly higher than those of
      sham operation rats (all P<0.01). CONCLUSION: Decreased expression of renal HSP72
      may contribute to activate the TLR4- initiating inflammatory signal pathway,
      attributing partly to the pathogenesis of hepatorenal syndrome in biliary
      cirrhosis.

PMID- 18093431
TI  - [Effects of reduced glutathione on contents of hydroxyproline and oxidation
      stress reaction in kidney of unilateral ureteral obstruction in rat].
AB  - OBJECTIVE: To explore therapeutic effect of glutathione (GSH) on unilateral
      ureteral obstruction (UUO) induced renal interstitial fibrosis and its mechanism
      in rat. METHODS: Thirty-six adult healthy Wistar rats were randomly divided into
      3 groups (each n=12): sham operation group, UUO group and GSH group. Rats in UUO
      group and GSH group underwent left unilateral ureteral ligation as described
      previously. Rats in sham group had their ureters manipulated but not ligated. In
      GSH group, GSH was injected intraperitoneally (100 mg.kg(-1).d(-1)) in different
      doses based on the animal's body weight, one day before UUO and then for
      consecutive 10 days after UUO. Meantime, same volume of physiological saline was
      given in sham operation and UUO groups as GSH group. Animals were sacrificed at
      10 days after surgery. The pathological changes in obstructed kidney tissue were
      observed with hematoxylin and eosin (HE) and Masson stains. The contents of
      hydroxyproline (Hyp) and total anti-oxygen capability (T-AOC) were measured by
      chemical colorimetry method, the activity of total superoxide dismutase (T-SOD)
      was assayed by a modified xanthine/xanthine oxidase method, and the content of
      malondialdehyde (MDA) was determined by thiobarbituric acid method. RESULTS: Ten
      days after UUO, swelling and atrophy in renal parenchyma of obstructed kidneys
      were clearly observed. Fibrous material and monocyte infiltration were increased
      in the interstitial space. Furthermore, thickening of interstitial space of the
      tubular basement membrane and widening of the interstitial space of the renal
      cortex were noted. Hypertrophy or atrophy of juxtaglomerular tubules were also
      observed. There were cellular or albumin casts in a part of tubules. Interstitial
      fibrosis was observed in obstructed kidneys 10 days after UUO. The data indicated
      that ureteral obstruction significantly increased the contents of Hyp and MDA,
      but decreased the content of T-AOC and T-SOD activity, as compared with sham
      operation group [Hyp: (0.524+/-0.132) microg/mg, T-AOC: (1.48+/-0.21) U/mg, T
      SOD: (12.77+/-0.76) U/mg, MDA: (2.65+/-0.32) nmol/mg, all P<0.01]. Compared with
      UUO group, pathological changes were milder and the contents of Hyp [(1.598+/-
      0.252) microg/mg vs. (1.027+/-0.196) microg/mg, P<0.05] and MDA [(4.58+/-0.59)
      nmol/mg vs. (3.26+/- 0.34) nmol/mg, P<0.05] were significantly decreased in
      kidney of GSH group, meanwhile the content of T-AOC was increased [(0.67+/-0.19)
      U/mg vs. (0.94+/-0.17) U/mg, P<0.05], but the content of T-SOD did not show any
      change [(9.39+/-0.87) U/mg vs. (9.41+/-0.93) U/mg, P>0.05]. CONCLUSION: Reduced
      glutathione treatment attenuates UUO-induced renal interstitial fibrosis via
      decreasing content of Hyp in UUO kidney and preventing oxidation stress injury.

PMID- 18093432
TI  - [The opportune time and implication of determining serum choline esterase in
      acute organophosphorous poisoning].

PMID- 18093433
TI  - [Effects of atorvastatin on expression of peroxisome proliferation activated
      receptor gamma in unilateral ureteral obstruction in rats].
AB  - OBJECTIVE: To observe the expression of peroxisome proliferation activated
      receptor gamma (PPAR gamma) at different periods in renal interstitium and to
      study the effect of atorvastatin on the protein expression of PPAR gamma in
      unilateral ureteral obstruction (UUO) in a rat model. METHODS: Forty-five female
      Sprague-Dawley (SD) rats were divided into three groups: the sham operation
      group, the model group and the atorvastatin group. The latter two groups
      underwent UUO and then received vehicle only or atorvastatin (10 mg.kg(-1).d(-1))
      by daily gastric gavage, from three days before the UUO operation to the day of
      sacrifice . The sham operation rats received vehicle. Five rats of each group
      were sacrificed respectively at 5, 10 and 15 days after surgery. Histological
      changes in renal tissue were observed by hematoxylin and eosin (HE) and Masson
      stain. Immunohistochemistry for PPAR gamma was performed in renal interstitium at
      each time point. RESULTS: Interstitial expansion and fibrosis in ureter
      obstructed kidney was prominent in the model group. Atorvastatin seemed to have
      ameliorated interstitial expansion and fibrosis in atorvastatin group. Detectable
      basic PPAR gamma expression was observed in renal inner medulla of rats in sham
      operation group, and it was mainly concentrated in collecting tubules. In UUO
      rats, PPAR gamma expression was found increased and extended to renal tubular
      epithelial cells. Increased PPAR gamma expression was found on the 5th day after
      UUO, and significant PPAR gamma expression was found on the 10 th day after UUO.
      The increased PPAR gamma expression was found to be downregulated on the 15 th
      day after UUO, but still significantly increased compared with that of the model
      group at the same time point (all P<0.01). Atorvastatin could significantly
      increase the expression of PPAR gamma as compared with the model group at each
      time point (all P<0.01). CONCLUSION: PPAR gamma expression was found increased,
      and it appeared in renal tubular epithelial cells in UUO rats, Atorvastatin may
      play a protective role in the kidney by activating PPAR gamma, thus alleviating
      renal interstitial fibrosis following UUO in rats.

PMID- 18093434
TI  - [Risk stratification and prognostic evaluation of patients with pulmonary
      thromboembolism].
AB  - OBJECTIVE: To explore the risk stratification and prognostic evaluation of
      pulmonary thromboembolism (PTE). METHODS: The clinical data of 46 patients
      suffering from PTE diagnosed by ventilation perfusion scan or spiral CT pulmonary
      angiography admitted to our hospital from January 2002 to December 2006 were
      analyzed retrospectively. RESULTS: The total mortality was 33% (15/46 cases). The
      mortality in the group whose cardiac troponin I was positive (n=11) was 82% (9/11
      cases), 17% (6/35 cases)when troponin I was negative (n=35). The mortality in
      normal electrocardiogram (ECG) group (n=14) and abnormal group (n=32) was 7%
      (1/14 cases) and 44% (14/32 cases) respectively. The mortality in the group with
      right ventricular dilatation (right ventricular diastolic dimension/left
      ventricular diastolic dimension > or =0.6) as shown by echocardiography (n=20)
      and without right ventricular dilatation (n=26) right ventricular diastolic
      dimension/left ventricular diastolic dimension<0.6) was 55% (11/20 cases) and 15%
      (4/26 cases) respectively. The mortality in the group whose pulmonary arterial
      obstruction index shown by spiral CT pulmonary angiography <0.6 (n=19) and > or
      =0.6 (n=11) was 5% (1/19 cases) and 91% (10/11 cases) respectively. The mortality
      between above groups showed statically significant difference (all P<0.05).
      CONCLUSION: Cardiac troponin I, ECG, right ventricular dilatation by
      echocardiography and pulmonary arterial obstruction index by spiral CT pulmonary
      angiography may be taken as indices for risk stratification and prognostic
      evaluation of patients with PTE, and they may be helpful in optimizing treatment
      strategies.

PMID- 18093435
TI  - [Molecular biologic study on heme oxygenase in experiment pulmonary
      thromboembolism].
AB  - OBJECTIVE: To investigate the changes in heme oxygenase (HO) system expression in
      pulmonary thromboembolism (PTE), and the influence to the pulmonary artery blood
      pressure as a result of the changes. METHODS: In 23 healthy adult male dogs,
      autologous thrombus was injected through the jugular vein to reproduce the PTE
      model. They were divided randomly into 4 groups: A (pulmonary embolism 3 hours
      group), B (pulmonary embolism 8 hours group), C (pulmonary embolism 24 hours
      group) and D (control group). Swan-Ganz catheter was placed via the femoral vein
      to observe the changes in hemodynamics. Pulmonary artery was obtained to detect
      the expression of HO-1 using semi-quantity reverse transcription-polymerase chain
      reaction (RT-PCR) and immunohistochemical method. RESULTS: The pulmonary artery
      mean pressure (PAMP), pulmonary artery systolic pressure (PASP) and pulmonary
      artery diastolic pressure (PADP) of the experimental groups were increased
      obviously after the pulmonary embolism as compared with those of before the
      embolism (all P<0.05), and were decreased obviously 1 hour after the embolism
      (all P<0.05). The decrease was gradual and stopped after 4-5 hours, but the
      pressure 8 hours after embolism was still higher than that of before embolism. HO
      1 was not expressed in pulmonary artery in control group, but expressed after
      embolism in each experimental group. The expression was increased gradually after
      pulmonary embolism, and it was remarkable 24 hours after embolism (all P<0.05).
      CONCLUSION: The expression of HO-1 increased in PTE, and the increased pulmonary
      artery blood pressure decreased at the same time. The results suggest that HO-1
      is related with dilatation of pulmonary artery after PTE.

PMID- 18093436
TI  - [Retrospective analysis of treatment of organic phosphorus pesticide poisoning, a
      report of 615 cases].

PMID- 18093437
TI  - [Role of neuron specific enolase and S100 protein in evaluation of brain damage
      in patients resuscitated from cardiac arrest].
AB  - OBJECTIVE: To investigate the prognostic value of serum neuron specific enolase
      (NSE) and S100 protein in evaluation of brain damage in patients resuscitated
      from cardiac arrest (CA). METHODS: According to whether the patients regained
      consciousness after 6 months or not, 25 patients after cardiopulmonary
      resuscitation (CPR) were divided into 2 groups, and blood samples were obtained
      for determination of NSE and S100 protein at 2, 12, 24, 48 and 72 hours after
      recovery of spontaneous circulation (ROSC), then the values at each time point
      were compared between 2 groups and also with that of 7 healthy volunteers.
      Receiver operator characteristic (ROC) curves of serum NSE and S100 protein were
      depicted and used area under curve (AUS) to scale the ability in evaluating the
      state of consciousness in patients after CPR. RESULTS: (1)The levels of serum NSE
      at 12, 48 and 72 hours and S100 protein at 2, 12, 48 and 72 hours were
      significantly higher in patients who did not regain consciousness compared with
      patients who regained consciousness (all P<0.01). (2)Compared with healthy
      volunteers, the levels of NSE at 12 and 24 hours and S100 protein at 12 hours
      were higher in patients who regained consciousness (all P<0.05), the levels of
      NSE at all time points and S100 protein at 12, 48 and 72 hours were significantly
      higher in patients who did not regain consciousness (P<0.05 or P<0.01). (3)Area
      under curve AUC(NSE) =0.848 (P=0.000), AUC(S100) =0.896 (P=0.000), therefore both
      serum NSE and S100 protein had diagnostic value for predicting whether patients
      resuscitated from CA could regain consciousness or not. Serum S100 protein cut
      off was 0.165 microg/L, with a sensitivity of 94.4%, a specificity of 100%, a
      positive predictive value of 100%, a negative predictive value of 80% and an
      accuracy of 95.5% at 2 hours after ROSC. Serum NSE cut-off was 45.6 microg/L, all
      values reached 100% 48 hours after ROSC. CONCLUSION: Measurement of serum NSE and
      S100 protein concentrations can help judge the degree of brain damage and whether
      patients can regain consciousness after CPR. It will be more valuable to
      prognosticate a serious and continuous brain damage with dynamic observation of
      the serum NSE together with S100 protein.

PMID- 18093438
TI  - [Experimental study on early pulmonary injury induced by severe acute
      pancreatitis in rats].
AB  - OBJECTIVE: To investigate the injury to pulmonary tissue induced by severe acute
      pancreatitis (SAP) during its early period. METHODS: Forty adult male Sprague
      Dawley (SD) rats weighing 300-400 g were randomly divided into 4 groups with 8
      animals in each group: sham operation group and 30, 60, 120 and 360 minutes after
      SAP groups. The model of SAP was reproduced by retrograde injection of 5% sodium
      taurocholate into the pancreatic duct of rats. Rats were sacrificed at different
      time points, and blood gas analysis, pulmonary pathological changes and wet dry
      weight ratio (W/D) of the lung were conducted. RESULTS: A large amount of
      polymorphonuclear neutrophils were observed in pulmonary tissue within 360
      minutes after reproduction of SAP with obvious changes, and water content of
      pulmonary tissue was increased significantly, while base excess (BE) decreased
      significantly in rats with SAP (P<0.05 or P<0.01 ). But no obvious change was
      observed in arterial partial pressure of oxygen (PaO(2)) and partial pressure of
      carbon dioxide (PaCO(2), both P>0.05). CONCLUSION: SAP causes significant
      inflammation in rat lung with injury to pulmonary tissue in its early period.

PMID- 18093439
TI  - [The application of the bedside blood purification technique in rescuing
      critically ill patients in sudden public health events: a report of 22 cases].

PMID- 18093440
TI  - [Discussion of diagnosis and treatment of 186 cases with abdominal trauma].

PMID- 18093441
TI  - [Clinical result of bedside artificial liver system in the treatment of liver
      failure patients].

PMID- 18093442
TI  - [The use of HA330-II microporous resin plasma adsorption in the treatment of
      chronic severe hepatitis].

PMID- 18093443
TI  - [Effects of benazepril and valsartan alone or in combination on proteinuria in
      chronic glomerular disease].

PMID- 18093444
TI  - [Experiences of craniectomy in the treatment of 36 cases of hypertensive
      cerebellar hemorrhages].

PMID- 18093445
TI  - [Clinical analysis of cause of terminal renal failure in senile patients and
      common complication of hemo-dialysis].

PMID- 18093446
TI  - [A study of the efficacy and medical costs of the use of hemoperfusion for the
      treatment of acute serious organic phosphorus poisoning].

PMID- 18093448
TI  - 'Cut down to quit' with nicotine replacement therapies in smoking cessation: a
      systematic review of effectiveness and economic analysis.
AB  - OBJECTIVES: To examine the effectiveness and cost-effectiveness of nicotine
      replacement therapy (NRT) for 'cut down to quit' (CDTQ) smoking. DATA SOURCES:
      Major electronic databases were searched up to July 2006. REVIEW METHODS: Data
      from studies meeting the criteria were reviewed and analysed. A decision
      analytical model was constructed to estimate the cost-effectiveness of CDTQ from
      the NHS perspective. RESULTS: No systematic reviews of the effectiveness of CDTQ
      and no randomised controlled trials (RCTs) specifically addressing CDTQ were
      identified. Seven randomised placebo-controlled trials satisfied the inclusion
      criteria; six of these were industry sponsored. However, sustained smoking
      cessation was only reported as a secondary outcome in these trials and required
      commencement of cessation within the first 6 weeks of treatment. Meta-analyses of
      the study level results demonstrated statistically significant superiority of NRT
      compared with placebo. Individual patient data from unpublished reports of five
      RCTs were used to calculate sustained abstinence of at least 6 months starting at
      any time during the treatment period (generally 12 months). From this the meta
      analysis indicated statistically significant superiority of NRT versus placebo
      [relative risk 2.06, 95% confidence interval (CI) 1.34 to 3.15]. The proportions
      achieving this outcome across all five RCTs were 6.75% of participants in receipt
      of NRT and 3.29% of those receiving placebo. The number-needed-to-treat was 29.
      This measure of sustained abstinence was used for economic modelling. No existing
      economic analyses of CDTQ were identified. A de novo decision analytic model was
      constructed to estimate the cost-effectiveness of making CDTQ with NRT available
      for smokers unwilling or unable to attempt an abrupt quit. The outcome measure
      was expected quality-adjusted life-years (QALYs). The model results suggest that
      CDTQ with NRT delivers incremental cost-effectiveness ratios (ICERs) ranging from
      around 1500 pounds/QALY to 7700 pounds/QALY depending on the age at which smoking
      cessation was achieved and the modes of CDTQ delivery. Assuming applicability to
      a single population, CDTQ was not cost-effective compared with abrupt quitting.
      If CDTQ with NRT were to be offered on the NHS as a matter of policy, the base
      case results suggest that it would only be effective and cost-effective if a
      substantial majority of the people attempting CDTQ with NRT were those who would
      otherwise make no attempt to quit. This result is robust to considerable
      variation in the forms of CDTQ with NRT offered, and to the assumptions about
      QALY gained per quit success. CONCLUSIONS: Meta-analysis of RCT evidence of quit
      rates in NRT-supported smoking reduction studies indicates that NRT is an
      effective intervention in achieving sustained smoking abstinence for smokers who
      declare unwillingness or inability to attempt an abrupt quit. The 12-month
      sustained abstinence success rate in this population (approximately 5.3% with NRT
      versus approximately 2.6% with placebo) is considerably less than that documented
      for an abrupt quit NRT regime in smokers willing to attempt an abrupt quit with
      NRT (which according to other systematic reviews is around 16% with NRT versus
      10% with placebo). Most of the evidence of effectiveness of CDTQ came from trials
      that required considerable patient-investigator contact. Therefore, for CDTQ with
      NRT to generate similar abstinence rates for this recalcitrant population in a
      real-world setting would probably require a similar mode of delivery. The
      modelling undertaken, which was based on reasonable assumptions about costs,
      benefits and success rates, suggests that CDTQ is highly cost-effective compared
      with no quit attempt. CDTQ remains cost-effective if dilution from abrupt
      quitting forms a small proportion of CDTQ attempts. In an alternative analysis in
      which smokers who switch from an abrupt quit to CDTQ retain the success rate of
      abrupt quitters, all forms of CDTQ appear cost-effective. Randomised trials in
      recalcitrant smokers allowing head-to-head comparison of CDTQ delivered with
      various modalities would be informative.

PMID- 18093447
TI  - A systematic review and economic model of switching from non-glycopeptide to
      glycopeptide antibiotic prophylaxis for surgery.
AB  - OBJECTIVES: To determine whether there is a level of methicillin-resistant
      Staphylococcus aureus (MRSA) prevalence at which a switch from non-glycopeptide
      to glycopeptide antibiotics for routine prophylaxis is indicated in surgical
      environments with a high risk of MRSA infection. DATA SOURCES: Major electronic
      databases were searched up to September 2005. REVIEW METHODS: The effectiveness
      review included controlled clinical trials comparing a glycopeptide with an
      alternative antibiotic regimen that reported effectiveness and/or adverse events.
      Controlled observational studies were also included for adverse events. The cost
      effectiveness review included economic evaluations comparing glycopeptide
      prophylaxis with any alternative comparator. Study validity was assessed using
      standard checklists. The supplementary economic reviews assessed evaluations of
      non-glycopeptide antibiotic prophylaxis; evaluations where antibiotic resistance
      is a problem; methods of modelling resistance in infectious diseases; and
      developing a conceptual framework. An indicative decision analytic model was
      developed to compare vancomycin with a cephalosporin and with a combination of
      vancomycin and cephalosporin, using hip arthroplasty as an exemplar. Available
      data on, for example, surgical site infection (SSI) rates, MRSA rates,
      effectiveness of the antibiotics, were incorporated into the model. Costs were
      estimated from the perspective of the NHS. RESULTS: The effectiveness review
      included 16 randomised controlled trials, with a further three studies included
      for adverse events only. There was no evidence that glycopeptides were more
      effective than non-glycopeptides in preventing SSIs. Most of the trials did not
      report either the baseline prevalence of MRSA at the participating surgical units
      or MRSA infections as an outcome. The cost-effectiveness review included five
      economic evaluations of glycopeptide prophylaxis. Only one study incorporated
      health-related quality of life and undertook a cost-utility analysis. None of the
      studies was undertaken in the UK and none explicitly modelled antibiotic
      resistance. The supplementary reviews provided few insights into how to assess
      cost-effectiveness in the context of resistance. No studies modelled cost
      effectiveness alongside epidemiological models of resistance. There was little
      information regarding the impact of surgical infections on costs post-discharge
      and patient quality of life. The lack of available clinical evidence limited the
      development of the cost-effectiveness model and meant that the modelling could
      only be indicative in nature. The model can be used to show the threshold
      baseline risk at which the use of vancomycin as prophylaxis might be cost
      effective (the model did not include teicoplanin). The indicative model suggests
      that the baseline risk of MRSA can be fairly modest at below the national average
      and it would still appear cost-effective to use glycopeptide prophylaxis. The
      model indicates that the use of glycopeptides as a form of prophylaxis in
      addition to a treatment for MRSA infections is unlikely to decrease the total
      usage and hence reduce the risk of future problems with glycopeptide-resistant
      bacteria. CONCLUSIONS: There is insufficient evidence to determine whether there
      is a threshold prevalence of MRSA at which switching from non-glycopeptide to
      glycopeptide antibiotic prophylaxis might be clinically effective and cost
      effective. Future research needs to address the complexities of decision-making
      relating to the prevention of MRSA and infection control in general. Research
      including evidence synthesis and decision modelling comparing a full range of
      interventions for infection control, which extends to other infections, not just
      MRSA, is needed. A long-term research programme to predict the pattern of drug
      resistance and its implications for future costs and health is also needed.

PMID- 18093449
TI  - Retrospective study of specific immunotherapy - what should be done in the
      future.
AB  - In this retrospective study, data on 241 atopic patients treated with specific
      cutaneous immunotherapy during the 1985-2006 period at Allergy Clinic, University
      Department of Dermatology and Venereology, were reviewed. The following diagnoses
      were recorded: atopic dermatitis, pure or in combination with allergic rhinitis
      or allergic bronchitis, or allergic bronchitis and asthma, allergic rhinitis,
      allergic conjunctivitis, urticaria, and Quincke's edema. The aim was to
      retrospectively analyze clinical efficacy and laboratory findings in atopic
      patients undergoing specific immunotherapy. Before specific immunotherapy
      administration, eosinophil count, immunoglobulins, skin prick test, total IgE
      (RIST) and specific IgE (IgE UniCAP) were determined. The following allergens
      were included in specific immunotherapy: Dermatophagoides pteronyssinus, house
      dust mite (mixed or separately), mixed and single pollens (grass, tree, weed),
      feather, and animal dander. The most frequent allergens in 241 atopic patients
      were grass pollen mixture, Dermatophagoides pteronyssinus, ragweed, tree pollen
      mixture, cocksfoot, birch, animal dander, and feather. Treatment efficacy was
      demonstrated after 3 years of continuous therapy by clinical evaluation and with
      the same diagnostic procedure. After several months of therapy, initial clinical
      improvement was noticed in atopic dermatitis patients as well as in patients with
      respiratory diseases that were sensitive to airborne allergens. According to
      literature, specific immunotherapy was used as a treatment option, which may
      affect the natural course of allergic diseases. It reduces development of asthma
      in patients with allergic rhinitis and prevents the onset of new sensitizations.

PMID- 18093450
TI  - A global look at sexually transmitted infections.
AB  - This paper will give a resume of many of the important factors, which form the
      immense problems in sexually transmitted infections in the world in 2007. STI is
      the term used to include sexually transmitted diseases and HIV/AIDS. It aims to
      enlighten both the specialist dermato-venereologist as well as all interested
      readers.

PMID- 18093451
TI  - Epidemiology of sexually transmitted diseases and infections.
AB  - Sexually transmitted diseases and infections (STDIs) are known to have a major
      socioeconomic and biologic impact, par notticularly on women (e.g., sterility,
      ectopic pregnancies, neo notplasms, etc.) and fetus (intrauterine and perinatal
      mortality, infection, malformations). Sex work noters do not use health services
      appropriately and are a high-risk category. Despite this evidence, data on
      prostitution and STDIs in some countries are limited. Sexual health medicine is
      involved in the community by identifying and minimizing the STDI problems through
      laboratory screening, diagnostic testing, education, and research.

PMID- 18093452
TI  - An unusual case of superficial lymphangioma of the right foot.
AB  - Superficial lymphangioma is a microcytic lymphatic malformation that is usually
      present already at birth. Women are more commonly affected than men are. It
      occurs because of the deep lymphatic circulation obstruction. Superficial
      lymphangioma is most commonly found in the mouth, especially the tongue, on the
      shoulders, neck, limbs, armpits and groin. It appears as a cluster of small firm
      blisters filled with clear or hemorrhagic lymph fluid, resembling frogspawn. We
      are presenting an unusual case of superficial lymphangioma of the right foot in
      an adult female patient.

PMID- 18093453
TI  - Unrecognized cicatricial pemphigoid with oral manifestations and ocular
      complications. A case report.
AB  - Cicatricial pemphigoid is an autoimmune bullous disease characterized by mucous
      membrane fibrosis with resulting scarring, predominantly in the conjunctival and
      oral mucosa, which rarely involves skin changes. The majority of patients present
      with painful erosions or desquamative scarring gingivitis, resulting in eating
      and drinking disorders. Typical ocular lesions include chronic scarring
      conjunctivitis with progressive subconjunctival fibrosis, fornix foreshortening
      and synechia formation between the bulbar and palpebral conjunctiva, occasionally
      resulting in blindness. A 69-year-old woman was admitted to our Department for
      intense pain and severe burning sensation in the oral cavity, induced by several
      erosions and solitary blisters, lasting for 3 years. She was also diagnosed with
      the right eye symblepharon, lid entropion, trichiasis, leukoma and blindness of
      the right eye. The diagnosis of cicatricial pemphigoid was based on clinical
      picture and histopathology combined with immunofluorescence methods, with therapy
      initiated thereupon. Systemic corticosteroid (methylprednisolone) therapy in
      combination with azathioprine proved successful in the treatment of oral lesions
      as well as for stabilization of ocular lesions. Unfortunately, the patient was
      diagnosed in the advanced stage when scarring had already occurred. Prompt
      recognition of cicatricial pemphigoid and close patient monitoring are an
      imperative for the future prognosis of the disease.

PMID- 18093454
TI  - Acneiform eruption induced by cetuximab.
AB  - Cetuximab is a recombinant human/mouse chimeric monoclonal antibody that targets
      the extracellular domain of the epidermal growth factor receptor (EGFR).
      Cetuximab is approved by the US Food and Drug Administration for the treatment of
      EGFR-expressing metastatic colorectal cancer as monotherapy in patients who are
      intolerant to irinotecan-based chemotherapy, or in combination with irinotecan in
      patients who are refractory to irinotecan-based chemotherapy. Due to the
      important role of the EGFR in skin homeostasis, cutaneous reactions are a common
      adverse effect of cetuximab, mainly as acneiform follicular eruption seen in
      almost 85% of patients. We report on a 46-year-old female Caucasian patient with
      metastatic colorectal cancer, referred to our department for acneiform eruption
      induced by cetuximab in combination with irinotecan. Four days after the first
      infusion the patient developed intense acneiform eruption consisting of
      erythematous follicular papules and pustules spread to the face, neck and upper
      part of the trunk, accompanied by intense pruritus and fever (38.0 degrees C).
      There were no comedones. Biopsy specimen revealed superficial and florid
      neutrophilic suppurative folliculitis. She was treated with erythromycin tablet
      600 mg, three times a day for 1 month, and topical clindamycin solution 3%. After
      1 month of treatment, the lesions consistently faded, and the patient continued
      receiving immunochemotherapy.

PMID- 18093455
TI  - Lofgren's syndrome presenting with erythema nodosum-like eruption.
AB  - Lofgren's syndrome is an acute form of sarcoidosis that mostly presents with
      erythema nodosum, periarticular ankle inflammation, arthritis, conjunctivitis,
      and unilateral or bilateral hilar or right paratracheal lymphadenopathy. Erythema
      nodosum is the most common cutaneous lesion in acute sarcoidosis, but it is
      histologically nonspecific, as it does not reveal sarcoidal granulomas upon
      microscopic examination. We present a case of a 57-year-old woman with acute
      onset of tender erythematous nodules on the calves, which were clinically
      erythema nodosum-like lesions. Histologic analysis revealed sarcoidal granulomas
      located in the dermis and subcutaneous tissue. Upon further work-up, the patient
      was found to have both pulmonary and ocular sarcoidosis. Based on this case, we
      recommend that all patients with erythema nodosum-like lesions undergo biopsy and
      further work-up for sarcoidosis is recommended in case of biopsy proven sarcoidal
      granulomas.

PMID- 18093456
TI  - Porphyria cutanea tarda as the most common porphyria.
AB  - Porphyrias are an uncommon, heterogeneous group of metabolic diseases caused by
      inherited or acquired deficiency of specific enzymes in the heme biosynthetic
      pathway resulting in an excess of porphyrins (red-brown pigments) and their
      precursors. Accumulation of heme precursors, such as porphyrinogens that are
      spontaneously oxidized to porphyrins, is responsible for various clinical
      features. Porphyrias are classified into three groups: erythropoietic, hepatic
      and hepatoerythropoietic, depending on the primary organ affected. Porphyria
      cutanea tarda (PCT) is the most common porphyria, characterized by defective
      uroporphyrinogen III decarboxylase enzyme. There are three types of PCT with
      typical skin manifestations. Patients with PCT present with skin fragility,
      erosions, vesicles, bullae, and milia in sun-exposed areas of the skin, sometimes
      periorbital mottled hyperpigmentation and hypertrichosis, sclerodermoid changes
      and ulceration. We present the most common pathogenetic, clinical, diagnostic,
      and therapeutic features of PCT and other types of porphyria.

PMID- 18093457
TI  - Azathioprine in dermatology.
AB  - Azathioprine is a synthetic purine analog derived from 6-mercaptopurine. It is a
      purine antagonist and its active metabolites act by disrupting the function of
      endogenous purines. It has a cytotoxic and immunosuppressive mechanism of action.
      It is used in dermatology for treatment of immunobullous diseases, generalized
      eczematous disorders and photodermatoses. There is an enzyme in the metabolism of
      azathioprine called thiopurine s-methyltransferase (TPMT). It is very important
      to measure the TPMT activity before initiating therapy so that proper dosing of
      azathioprine can be achieved.

PMID- 18093458
TI  - What should we know about hypersensitivity to peanuts in topical preparations.

PMID- 18093460
TI  - Desmoglein story from Masayuki Amagai teach us how to discover the beauty of
      nature.

PMID- 18093461
TI  - Seeing obesity as a systems problem.
AB  - Obesity has reached epidemic proportions in many countries and persists despite
      continuing efforts to find solutions. Such 'stubborn problems' often signal the
      influence of 'feedback systems'. In the case of the obesity epidemic, this
      possibility can be investigated using available system analysis tools. The
      investigation must begin with a study of the interplay between the full range of
      human and environmental factors. This paper outlines the nature of feedback and
      briefly discusses some of its management implications. A practical way to
      initiate a 'systems approach' to the obesity problem is suggested and four
      principles to guide the management of complex human- environment systems are
      presented.

PMID- 18093462
TI  - Too busy: why time is a health and environmental problem.
AB  - Time pressure is emerging as a modern malaise. It is linked to changes in working
      life, with longer work hours and faster work pace, and it is compounded in
      families; nowadays both parents must combine working with caring. Time pressure
      also challenges urban, health and environmental policy because many interventions
      have an unacknowledged time dimension. People need time to keep healthy, to
      exercise and to maintain strong social and family bonds. If urban designs or
      environmental solutions can reduce time demands they may directly improve health
      and social outcomes. However, where they increase time demands they may have
      unanticipated health costs, create disincentives for the uptake of interventions
      and disadvantage those who are most time poor.

PMID- 18093463
TI  - 'Crowded suburbs' and 'killer cities': a brief review of the relationship between
      urban environments and mental health.
AB  - Most of the world's population now lives in cities, with 90% of Australians
      living in urban settlements of more than 10 000 people. Urban environments help
      shape population health, particularly among disadvantaged people, where poor
      health is concentrated. A growing body of research has focussed on the
      association between cities and mental health. Three hypotheses have been proposed
      to explain this association: psychosocial stressors; concentrated disadvantage;
      and social drift. It remains unclear, however, how the characteristics of urban
      environments are related to each other and to mental health, and what might be
      the pathways underpinning the experience of different individuals. With one in
      five Australian adults meeting the diagnostic criteria for a mental disorder each
      year, investigation of the relationship between urban environments and mental
      health is urgently needed. This paper briefly reviews recent studies linking
      disadvantaged urban environments with mental health and proposes a hypothetical
      model to help guide future research.

PMID- 18093464
TI  - Healthy by Design: an innovative planning tool for the development of safe,
      accessible and attractive environments.
AB  - The Healthy by Design guidelines were developed by the National Heart Foundation
      of Australia in 2004 to assist planners to deliver plans for residential
      developments that support active living. This article provides an overview of the
      contents of this resource. It also provides examples of its application and
      influence in the planning sector.

PMID- 18093465
TI  - Public health and the potential benefits of Crime Prevention Through
      Environmental Design.
AB  - Studies have consistently found that safety and security are major public
      concerns; however, crime is rarely considered as an outcome in public health. The
      recent shift by planning policy towards promoting compact, 'walkable' communities
      close to public transport aims to redress many of the problems associated with
      urban sprawl. However, communities that do not feel safe are less likely to be
      active citizens. This paper argues that Crime Prevention Through Environmental
      Design has potential benefits for public health in the provision of local crime
      risk assessments and in delivering safer environments, which can support active
      living, walkable communities and public health.

PMID- 18093467
TI  - New hope for diabetics: adult blood stem cells can make insulin.
AB  - Human blood stem cell-derived insulin-producing cells can be easily isolated from
      autologous blood based on their unique phenotype. They act as pancreatic islet
      beta-cell progenitors, as demonstrated by authentic insulin production and homing
      to diabetic pancreatic islets. Clinical application of these autologous blood
      derived insulin-producing cells holds great promise for diabetic treatment.

PMID- 18093466
TI  - Can the impact on health of a government policy designed to create more liveable
      neighbourhoods be evaluated? An overview of the RESIDential Environment Project.
AB  - There is growing interest in the impact of community design on the health of
      residents. In 1998, the Western Australian Government began a trial of new
      subdivision design codes (i.e. Liveable Neighbourhoods Community Design Code)
      aimed at creating pedestrian-friendly neighbourhoods to increase walking, cycling
      and public transport use. The trial provided a unique opportunity for a natural
      experiment to evaluate the impact of a government planning policy on residents.
      Nevertheless, evaluations of this kind present a number of methodological
      challenges in obtaining the highest quality evidence possible. This paper
      describes the RESIDential Environment Project's study design and discusses how
      various methodological challenges were overcome.

PMID- 18093468
TI  - Magnetic nanoparticles: prospects in cancer imaging and therapy.
AB  - Nanotechnology based on the use of submicronic particles of inorganic and/or
      organic origin has the potential to revolutionalize the clinical management of
      cancer; the possibility of real time monitoring of disease progression and
      effects of therapy is now real. Especially, iron oxide super paramagnetic
      nanoparticles have shown clinical utility in cancer imaging and drug delivery and
      some formulations are now FDA-approved for use in the clinic. The prospects of
      magnetic nanoparticles in cancer imaging and treatment are reviewed.

PMID- 18093469
TI  - Molecular and genetic profiling in human gliomas.
AB  - Glioblastoma multiforme is the most aggressive fatal brain tumor with a median
      survival of about a year after diagnosis. The current available treatment options
      only marginally improve patient outcome. The complexity and heterogeneity of the
      disease pose an extensive challenge to the development of novel therapeutic
      agents. Through molecular and genetic profiling, it has been possible to both
      identify mechanisms of disease progression and its therapeutic resistance. This
      paper highlights the significance of these advances.

PMID- 18093471
TI  - Universal tumor antigens for cancer vaccination: targeting telomerase for
      immunoprevention.
AB  - Despite their much-heralded clinical potential, therapeutic cancer vaccines have
      thus far failed to achieve the necessary clinical benchmarks to allow their
      regulatory approval. In contrast, vaccination against infectious pathogens
      represents one of the biggest achievements of modern medicine, and in certain
      cases such as vaccines against the human papilloma virus or hepatitis B virus,
      vaccination may impact the development of cancer. To the extent that these two
      approaches differ as immunotherapy vs. immunoprevention, the challenge is to
      rethink the types of non-viral antigens that are currently being targeted in
      cancer vaccines. Immunological analysis suggests that the telomerase reverse
      transcriptase hTERT is a widely applicable target recognized by T lymphocytes and
      a prototype for a novel class of universal tumor antigens. Findings from initial
      clinical trials demonstrate that hTERT-specific immune responses can be safely
      induced in cancer patients. If the amplitude and duration of cellular immunity
      against hTERT can be optimized without toxicity in humans, then an opportunity
      exists to test hTERT vaccination as a way to reduce the risk of cancer recurrence
      in patients or even the risk of developing cancer in otherwise healthy
      individuals.

PMID- 18093470
TI  - Bioterror, agroterror, and new diseases.
AB  - As research techniques and biotechnology advance, the risk for potential
      bioterrorism increases due to the ease of creating or modifying virulent
      pathogenic microorganisms. In addition, the destruction of natural habitats to a
      range of animals and microbial species that are normally sequestered in these
      areas may bring forth new diseases to humans.

PMID- 18093472
TI  - In search of novel treatments for peripheral neuropathies and nerve regeneration.
AB  - Currently, we do not have effective therapies aimed at preventing or reversing
      axonal degeneration seen in peripheral neuropathies. Drug development programs
      should be aimed at understanding mechanisms of distal axonal degeneration and
      take into account the critical role Schwann cells play in axonal maintenance and
      nerve regeneration.

PMID- 18093473
TI  - Therapeutic targeting of the alpha-secretase pathway to treat Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a progressive and degenerative disorder
      pathophysiologically characterized by the accumulation of beta-amyloid peptides
      (A-beta) in the brain. A-beta is indicated to be the primary agent in the
      pathogenesis of AD. A-beta is generated from the amyloid precursor protein (APP)
      via two proteolytic enzymes, beta- and gamma-secretases. Alpha-secretase conducts
      an alternative proteolytic cleavage that prevents A-beta production and
      accumulation. Elevating levels of alpha-secretase cleavage, therefore, is a
      potential therapeutic strategy to treat AD.

PMID- 18093474
TI  - Pharmacotherapy for prostate cancer: the role of hormonal treatment.
AB  - The role of hormonal therapy in the management of prostate cancer has been known
      for almost half a century. However, many controversies exist regarding the place
      and timing of androgen deprivation therapy. An increasing spectrum for the use of
      androgen deprivation therapy has been assessed, including multimodal treatment
      with radiation therapy. New approaches to androgen deprivation have been
      explored, including LHRH (luteinizing hormone-releasing hormone) antagonists and
      improved depot formulations. Recent evidence about the chemo-sensitivity of
      prostate cancer has opened avenues for treatment of hormone refractory disease
      and the combination of hormonal and chemotherapy is being studied at various
      stages of the disease. We explore the evidence, controversies and future of
      androgen deprivation therapy and critically reexamine the dogmas surrounding
      hormone therapy for prostate cancer.

PMID- 18093475
TI  - [Diagnostic value of E-cadherin, MMP-9, activated MMP-13 and anti-p53 antibodies
      in squamous cell carcinomas of head and neck].
AB  - BACKGROUND AND OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is a
      malignant tumor of epithelial origin, which currently represents a major socio
      sanitary problem since about 500,000 new cases are reported worldwide every year.
      In Spain, the HNSCC incidence exceeds 40 cases out of 100.000 individuals/year.
      HNSCC mortality is closely related to both local relapse and regional or distant
      lymphatic metastasis. Any reliable tumor-specific biomarker to predict
      preoperatively HNSCC relapse or lymphatic spread is not currently available. To
      date, several diagnostic procedures (imaging technologies, biochemical markers)
      have not shown enough potential to predict the presence of lymph node metastasis.
      There are new tumor markers related to the metastatic spread that have not been
      yet evaluated in HNSCC. The main goals of the present study was to determine an
      specific and reliable serum biomarkers pattern for HNSCC diagnosis, and to
      predict the HNSCC evolution before surgical therapy by developing appropriate
      biomarkers related to local relapse and lymphatic metastasis. MATERIAL AND
      METHOD: Thirty nine serum samples of HNSCC patients were collected during every
      neoplasm resection. Another 10 serum samples were collected from healthy
      individuals as a control group. Selected serum biomarkers were: soluble E
      cadherine, metalloproteinases (MMP) 2, MMP-9, active MMP-13; and Ac anti-p53.
      RESULTS: High serum levels of soluble E-cadherine, MMP-9, active MMP-13, and
      presence Ac anti-p53 were found to be significantly different from those in the
      control group. There was a statistic association with MMP-2 levels below 290
      ng/ml and poor survival. We also found significant differences between active MMP
      13 (levels > 685 pg/ml) and the presence of anti-p53 antibodies with the presence
      of lymph node metastasis. The multimarker analysis using both tumor markers
      provided the better sensibility (76%) and specifity (100%) values. CONCLUSIONS:
      The combined determination and valuation of tumor markers could improve the
      potential diagnosis of lymph node metastasis in HNSCC.

PMID- 18093476
TI  - [Metabolic syndrome prevalence and its association with the body mass index in
      university students].
AB  - BACKGROUND AND OBJECTIVE: Few studies exist about metabolic syndrome (MS) in
      young Mexican adult populations. The prevalences of overweight, obesity, and MS
      were evaluated in a sample of university students from Veracruz, Mexico. SUBJECTS
      AND METHOD: Transversal analytical study performed in 402 student of new
      admission, aged 20-29 years belonging to Veracruzana University. Waist
      circumference, systolic and diastolic blood pressures, and serum glucose,
      triglycerides, and high-density lipoproteins (HDL)-cholesterol were determined.
      The MS was diagnosed applying the current National Cholesterol Education Program
      Adult Treatment Panel III (NCEP-ATP-III) criteria. RESULTS: Male subjects showed
      higher values of waist circumference, weight, stature, body mass index (BMI),
      triglycerides, and systolic and diastolic blood pressures (p < 0.005, in all
      cases). The prevalence of central obesity was 9.5%; hypertriglyceridemia, 13.2;
      low HDL-cholesterol, 28.9%; high systolic and diastolic blood pressures, 9.2%;
      and hyperglucemia, 6.0%. 48% showed 1-4 NCEP-ATPIII criteria for MS. Global
      prevalence of MS was 3.7%. The BMI inclusion increased the MS prevalence in
      overweight and obese student (8.2 vs 0.8%) (x2 = 14.6; p < 0.001; odds ratio =
      10.8; 95% confidence interval, 2.4-48.8). CONCLUSIONS: The BMI inclusion improved
      the MS diagnostic in young adults. Because almost half of the subjects presented
      at least one MS factor, the need of preventive implementations in young
      populations and to develop longitudinal studies to ascertain the effect of MS
      later in life is suggested.

PMID- 18093477
TI  - [Bacteremia in outpatients: a 10-year period follow-up].
AB  - BACKGROUND AND OBJECTIVE: To know the incidence of bacteremia in outpatients
      (BO), their clinical and epidemiological characteristics and evolution. PATIENTS
      AND METHOD: We have analyzed the percentage of positive blood cultures and BO in
      a 10 year period. We have collected year, month, age, gender, first diagnosis,
      risk factors for bacteremia, microrganism, final diagnosis and diagnosis
      concordance. The bacteremia was classified by origin in: urinary tract infection,
      respiratory, abdominal, venous catheter (IVC), skin, endocarditis, bacteremia
      without an apparent focus (BWAF) and miscellaneous. We have compared the
      characteristics of the patients with and without diagnosis concordance. RESULTS:
      We have collected 283 episodes. The percentage of positive blood culture remained
      wi-thout changes and the percentage of BO tended to decrease. The most prevalent
      bacteria was Escherichia coli (56.5%) and the most frequent origin was urinary
      (59.7%) and BWAF (19.7%). There was no concordance between diagnoses in 37.1%.
      30.3% of patients were admitted. Urinary tract infection was detected in 93.5% of
      the cases, IVC in 6.2% and BWAF in 0%. With regard to the risk factors of
      bacteremia, human immunodeficiency infection tended to decrease and neoplasm to
      increase during the study period. CONCLUSIONS: In our experience, BO tends to
      decrease. The management of urinary infection seems adequate, and IVC could be
      improved. The main challenge is the cases of BWAF.

PMID- 18093478
TI  - [Therapeutics issues in osteoporosis].

PMID- 18093479
TI  - [Clinical value of head and neck tumor markers].

PMID- 18093480
TI  - [Evaluation of the clinical competence of Catalonian medicine schools 1994-2006.
      Evolution of examination formats until the objective and structured clinical
      evaluation (ECOE)].

PMID- 18093481
TI  - [Multifactorial treatment of atherosclerosis].
AB  - Cardiovascular diseases, the clinical paradigm of atherosclerosis, are the
      primary cause of mortality in developed countries. The origin of the atheromatous
      lesion is multifactorial, as it is the therapeutic approach to its prevention and
      clinical complications. The initial symptoms of ischemia in a vascular bed are
      usually evident when the atherosclerotic process is very advanced, being
      indicative of a diffuse disease and of an elevated future risk for ischemic
      events in other vascular territories. We perform this review in this clinical
      scenario, highlighting the preventive and therapeutic aspects of demonstrated
      clinical efficacy, with no detail of those treatments with benefit insufficiently
      proven.

PMID- 18093483
TI  - [Analysis of predictive value of Framingham-REGICOR and SCORE functions in
      primary health care].

PMID- 18093482
TI  - [Rituximab as treatment for thrombocytopenic thrombotic purpura associated with
      systemic lupus erythematosus].

PMID- 18093484
TI  - [Spondylodiscitis in SAPHO syndrome].

PMID- 18093485
TI  - [Anti-citrulline antibodies and treatment with anti-tumor-necrosis-factor-alpha
      and rituximab].

PMID- 18093486
TI  - [Fulminant meningococcemia].

PMID- 18093488
TI  - [Pulmonary hypertension: new insights from techniques imaging].
AB  - Pulmonary hypertension is a very serious condition, with 10-year survival rates
      under 10%. Despite this, knowledge of the pathophysiological mechanisms
      underlying its development and progression has been seriously limited by a lack
      of appropriate tools for studying the condition. The introduction of new
      noninvasive high-resolution imaging techniques, such as magnetic resonance
      imaging, could provide a promising new approach to the investigation of not only
      the anatomical, but also the functional and molecular, features of pulmonary
      hypertension. As has happened with atherosclerotic disease in recent years, high
      resolution imaging, combined with other imaging techniques such as computed
      tomography (CT) and positron-emission tomography, could provide useful data on
      morphological and physiological factors of fundamental importance to
      understanding unresolved issues concerning the etiology, diagnosis, and treatment
      of patients with pulmonary arterial hypertension. Moreover, the application of
      molecular techniques is leading to the development of a new discipline, molecular
      imaging, that will enable patients to be studied from a biological perspective
      and which could uncover mechanisms of great clinical relevance in experimental
      models. The key to the treatment of pulmonary arterial disease could be
      discovered by studying these mechanisms. For example, knowledge of the pathways
      involved in the development of endothelial dysfunction or in endothelial repair
      associated with bone marrow-derived cells--a common feature of a number of
      cardiovascular conditions--could lead to treatments that are able to stimulate
      endothelial replacement with circulating progenitor cells in patients with
      pulmonary arterial hypertension of whatever etiology.

PMID- 18093489
TI  - [Inappropriate sinus tachycardia: an update].
AB  - Inappropriate sinus tachycardia (IST) is an uncommon form of arrhythmia which is
      characterized by an exaggerated increase in heart rate that is out of proportion
      to normal physiologic demands. Usually, IST is triggered by orthostasis, minimal
      exertion, and psychological stress. The etiology of IST remains ill-defined.
      However, proposed mechanisms include: enhanced sinus node automaticity,
      alterations in autonomic function associated with increased sympathetic activity
      or reduced parasympathetic activity, and impaired baroreflex control. Recently,
      increased levels of autoantibodies to beta-adrenergic receptors have been
      observed in patients with IST. The clinical presentation of IST is highly varied
      and ranges from short episodes of palpitations associated with dyspnea, atypical
      precordial pain, cephalalgia, fatigue, and occasional syncope and presyncope to
      incapacitating incessant tachycardia. In general, IST is a diagnosis of
      exclusion. It is important that other causes of sinus tachycardia are excluded
      before making a diagnosis. Evaluation of autonomic function is essential for a
      diagnosis of IST. Treatment of IST is based on autonomic function findings and
      involves multidisciplinary management, including cardiac rehabilitation. Control
      and restitution of normal autonomic function is essential. The prognosis is
      benign though regular follow-up is required to optimize therapy.

PMID- 18093490
TI  - [Disease management programs in heart failure. Findings of the DIAL study].
AB  - Despite significant advances in the treatment of heart failure, patients' quality
      of life and prognosis are still poor. Hospitalization for decompensated heart
      failure or due to other causes is frequent in these patients and places a heavy
      financial burden on the healthcare system. The shortcomings of ambulatory
      treatment have led to the implementation of disease management programs whose aim
      is to optimize quality of care and treatment adherence, thereby improving
      clinical outcome and prognosis, and reducing healthcare costs. The multicenter
      randomized DIAL study compared treatment administered by means of a centralized
      telephone intervention by trained nurses with usual care in 1518 ambulatory
      patients with stable chronic heart failure who were receiving appropriate medical
      treatment and were being followed up by a cardiologist. This intervention proved
      effective in increasing treatment adherence, in reducing hospitalization due to
      heart failure or any cause, in improving quality of life, and in reducing costs.
      The findings of the DIAL study add to existing evidence that disease management
      programs have clinical benefits in patients with chronic heart failure and
      support their use as part of the strategy for ambulatory care in this population.

PMID- 18093491
TI  - [Risk stratification in acute coronary syndromes: an unresolved issue].
AB  - Risk stratification in patients with acute coronary syndrome has several
      objectives: to inform and provide advice to patients and their families; to
      identify patients at a high risk of death or myocardial infarction whose
      prognosis can be improved by appropriate treatment; to identify those with a very
      low risk who do not need invasive studies, thereby avoiding unnecessary cost and
      the risk associated with these procedures; and to formulate cardiac
      rehabilitation and secondary prevention measures following an acute event. During
      the last decade, a number of predictive models, or algorithms, have been
      developed in an attempt to predict death or myocardial infarction in patients
      admitted for acute coronary syndrome, with or without ST-segment elevation. The
      aim was to enable treatment to be adapted to the individual's risk. The best
      known models are: GRACE, PREDICT, TIMI, In-TIME, CPP, GUSTO and PURSUIT. Most of
      these models suffer from limitations that derive from the particular population
      group from which they were extrapolated or from the limited number of clinical
      variables used. Consequently, their application to the general unselected
      population with a high rate of comorbid conditions is not helpful for predicting
      risk in individual patients. Moreover, these algorithms have not taken into
      account other important factors that could influence prognosis, such as
      atherosclerotic disease burden or the degree of vascular inflammation. By taking
      all these factors into consideration and by employing the most up-to-date
      statistical techniques, more comprehensive and more clinically applicable models
      could be devised in the future.

PMID- 18093492
TI  - [Optimizing antithrombotic therapy in non-ST-elevation acute coronary syndrome].
AB  - The acute coronary syndromes (i.e., ST-segment elevation myocardial infarction,
      non-ST-segment elevation myocardial infarction, and unstable angina) share a
      common pathophysiology: the rupture or breakdown of atheromatous plaque
      superimposed on intracoronary thrombosis (i.e., atherothrombosis). The aim of
      this review article was to summarize developments occurring during the last year
      in antithrombotic therapy for non-ST-segment elevation acute coronary syndromes.
      Four specific issues are considered: pretreatment with clopidogrel before
      percutaneous coronary intervention, antiplatelet resistance, indications for
      glycoprotein IIb/IIIa inhibitors in patients pretreated with clopidogrel, and the
      role of bivalirudine and fondaparinux in the treatment of these patients.

PMID- 18093493
TI  - [Introduction to cutaneous bacterial infections].
AB  - Cutaneous bacterial infections are a very common disease seen in the dermatology
      consultation. The dermatologist cannot be unknowledgeable about primary skin
      infections due to Staphylococcus and Streptococcus, about the mechanisms by which
      the infection is produced and the host response. Molecular microbiology has made
      it possible for us to determine the true extent of the skin flora. Knowledge of
      this almost makes it possible to determine the limits of the secondary bacterial
      infections. Septic vasculitis is another field of special interest due to its
      repercussion in morbidity and mortality. Finally, together with the classical
      antimicrobials, there is a new generation of antibacterial drugs, both topic
      (retapamulin) and systemic (linezolid, daptomycin) ones, that augur a promising
      future in the management of the patients who have cutaneous bacterial infections.

PMID- 18093494
TI  - [Primary cutaneous infections due to Staphylococcus and Streptococcus].
AB  - Pyodermitis constitutes a very important chapter in dermatological practice. Its
      pathogenesis, in special the one caused by S. aureus, has improved due to the
      knowledge of the role developed by the host defensins, quorum-sensing signaling
      and the Panton-Valentine leucocidin gene among others. As well, exfoliative
      toxins and enterotoxins responsible for the staphylococal scalded skin syndrome
      (SSSS) and toxic shock syndrome, respectively, have been cloned. Also, it has
      been seen that bullous impetigo, SSSS and pemphigus foliaceus share a common
      target: desmoglein-1. The Panton-Valentine leucocidin gene has been related to
      the appearance of abscesses, necrotic cutaneous lesions and furuncles in young
      persons caused by meticillin resistant S. aureus, with its epidemiological
      implications. Finally, some atypical forms of erysipelas suppose a diagnostic
      challenge for the dermatologist.

PMID- 18093495
TI  - [Normal cutaneous flora and secondary bacterial infection].
AB  - Normal skin microflora consists of those micro-organisms which are usually
      present on the skin, without causing infection. The infant's skin colonization
      starts during birth and after the first months of life the skin microbiota is
      composed of the same micro-organisms as in the adult. The skin microflora is
      composed of bacteria, mostly gram-positives Staphylococcus species, yeasts which
      the most prevalent is Malassezia, viruses and arthropods like Demodex
      folliculorum. In the last years, the development of molecular microbiology and
      specially techniques like amplification and comparison of 16S rRNA, have
      demonstrated that cutaneous microbiota is composed of a higher diversity of
      bacteria than the traditionally observed in culture methods. We also review the
      main secondary bacterial skin infections.

PMID- 18093496
TI  - [Septic vasculopathy].
AB  - Sepsis is one of the commonest causes of death around the world. The real
      frequency of cutaneous lesions in the setting of sepsis is unknown, but when they
      appear, they are usually one of the earliest signs of sepsis, thus allowing a
      rapid diagnosis of this potentially life-threatening condition. Four are the main
      physiopathologic mechanisms that can induce cutaneous lesions in sepsis: a)
      disseminated intravascular coagulation; b) direct vessel wall invasion by the
      microorganism; c) immune-mediated vasculitis, and d) septic embolism. We know
      that more than one of these mechanisms can appear in one single patient. In this
      review, we analyse these four mechanisms, their clinical presentation, and the
      histological findings that can be found in the cutaneous biopsy.

PMID- 18093497
TI  - [Topical antimicrobial agents in dermatology].
AB  - Topical antimicrobial agents are chemical substances that, directly applied to
      the skin, inhibit the growth or destroy any microorganism, either fungi, viruses
      or bacteria. Within this term, we generally refer to those that are active
      against the latter. They are divided into antiseptics and antibiotics.
      Antiseptics are directly applied to a living organism to eradicate the existing
      microorganism on the mucocutaneous surfaces, preventing their proliferation.
      Topical antibiotics are either produced by living organisms or manufactured
      through synthesis and are mainly used to fight infections. Topical antimicrobials
      represent an important option in the prophylaxis and treatment of primary and
      secondary superficial bacterial infections. Antibiotics for topical use have a
      lower incidence of systemic toxicity, secondary effects and development of
      resistance than parenteral antibiotics. The ideal topical antimicrobial must have
      a broad spectrum of activity, fast and prolonged antibacterial effect,
      bactericidal activity, easy diffusion through tissues and detritus, with minimal
      toxicity, very low or null incidence of irritation or allergy and sparse activity
      against normal skin flora. The approach of this article is the description of the
      classical and new antimicrobials that are, more important due to their wide use
      and proven efficacy. We review their pharmacological characteristics, spectrum of
      activity, possible secondary effects and interactions, as well as the
      combinations that improve their antimicrobial activity, main indications and
      possible development of resistance, all this properly documented.

PMID- 18093498
TI  - [Systemic treatment of bacterial infections].
AB  - In the last years, there has been a great increase of bacterial resistance to the
      most frequently used antibiotics. Several factors should be considered when
      deciding to treat a cutaneous infection with a systemic treatment:
      characteristics of the patient, infection severity, prevalence and local
      resistance patterns of pathogens, and properties of available drugs.

PMID- 18093499
TI  - [The network of research info preventive activities and health promotion: a
      challenge for primary care].

PMID- 18093500
TI  - [Alcohol, wine, and health: myths and realities].

PMID- 18093501
TI  - [Identification of new and emerging technologies].
AB  - OBJECTIVE: Analyze the correspondence between health technologies (HT) to develop
      --doctor's opinion-- and the ones assessed by Spanish Agencies for Health
      Technologies Assessment. DESIGN: Response analysis of HT obtained from
      participant doctors. Comparison with assessment reports of agencies. SETTING:
      Andalusian Public Health System; 2003. Spanish Agencies for Health Tecnologies
      Assessment. PARTICIPANTS: One hundred and forty-seven specialised doctors of 46
      MIR specialties. METHOD: Non-random sample. Andalusian experts and leaders
      professional selected. Exhaustive searching in Internet or assessment reports of
      HT. A "score of effort" (SE) was calculated for each Agency. RESULTS: Seven HT
      groups agree with agency assessment reports: systems and communication network
      (SE, 0.78%-6.25%); mollecular biology for diagnosis and treatment (SE, 3.12%
      42.73%); functional image technologies, monitorization, quick diagnosis, and non
      invasive methods (SE, 3.93%-31.25%); lasertherapy, microsurgery, endoscopic
      surgery, minimally invasive, virtual and remote-controlled surgery (SE, 3.22%
      31.25%); stem cells, artificial organs, and xenotransplantation (SE, 0.78%
      12.34%); psychosocial interventions (SE, 0.78%-7.69%); management, planification
      and record systems (SE, 9.67%-76.92%). Two additional cathegories not cited by
      doctors but evaluated by agencies were identified: Effectiveness of therapeutic
      and disgnostic implanted strategies and sterilization methods of surgical
      material (SE, 3.86%-43.18%); Matural drugs, alternative therapies (SE, 1.78%
      6.25%). CONCLUSIONS: Greater concordance between doctors and agencies in:
      mollecular biology, functional image technology, new surgical techniques and
      management, planification and record systems.

PMID- 18093503
TI  - [Follow-up and monitoring of hypertension. Is this performed the same in the
      autochthonous and immigrant populations?].
AB  - OBJECTIVES: To evaluate the degree of control of blood pressure (BP) in the
      autochthonous and immigrant populations and to find the variables linked to good
      control. DESIGN: Cross-sectional, observational study. SETTING: Urban primary
      care team, Spain. PARTICIPANTS: All patients with hypertension seen between
      1/1/2000 and 1/7/2005 and whose origin was known: 1.063 patients in all, 931
      autochthonous and 132 immigrant ones. MAIN MEASUREMENTS: The main variable was
      hypertension control the last time BP was taken (BP </=140/90 mm Hg and </=130/80
      mm Hg in diabetics). In addition, data on country of origin, age, gender, body
      mass index, cardiovascular risk factors (diabetes, lipaemia, tobacco dependency),
      further examinations (annual blood analysis and ECG every 2 years) and prescribed
      medication were recorded. Logistic regression was used to calculate the effect of
      origin on blood pressure monitoring. RESULTS: Good BP control was achieved in
      39.2% of autochthonous patients and 25% of immigrants (odds ratio [OR], 1.6; 95%
      confidence interval [CI], 95% CI, 1.2-2.1). Nevertheless, multivariate analysis
      indicated age (OR, 1.029; 95% CI, 1.017-1.040) as the sole factor determining
      good or bad BP control. CONCLUSIONS: The origin of the patient does not affect BP
      control.

PMID- 18093504
TI  - [Predictive value of ultra-sound densitometry as a method of selective screening
      for osteoporosis in primary care].
AB  - OBJECTIVE: To determine the cut-off point of calcaneous quantitative ultrasound
      densitometry (QUS) as a selection method in primary care for referral of
      postmenopausal women for dual energy x-ray absorptiometry (DXA). DESIGN:
      Diagnostic techniques trial. SETTING: Four general practices in the Basque
      Country Autonomous Region, Spain. PARTICIPANTS: Randomly selected Caucasian women
      older than 45, chosen at random. A sample size of 146 women was used.
      INTERVENTIONS: Calcaneous ultrasound bone mineral density (BMD) measurement,
      using Achilles Express(R) and DXA. PRINCIPAL MEASUREMENTS: T-score BMD
      measurement on both devices. The sensitivity, specificity and positive predictive
      values of QUS and finally the ideal cut-off value were calculated. RESULTS: The
      mean age of the sample was 58.2 (17.7) (range, 48-83 years old). The prevalence
      of women with osteoporosis, osteopaenia and normal DXA was 14.1%, 50.4% and
      35.5%, respectively. The estimated sensitivity of QUS was 78.9% (56.7-91.5) and
      the specificity was 64.7% (55.6-72.8). The negative predictive value (NPV) was
      94.9% (87.7-98.0) and the positive predictive value (PPV) was 26.8% (17.0-39.6).
      After the COR curve analysis, the ideal cut-off for QUS was determined as a T
      score </= -2.0. CONCLUSIONS: Given its high NPV, QUS can be considered a useful
      device for screening before DXA. Its low PPV means it has to be combined with
      other complementary or substitutive selective screening methods, such as
      predictive rules, which should be evaluated in each specific use.

PMID- 18093505
TI  - [Therapy compliance in cases of hyperlipaemia, as measured through electronic
      monitors. Is a reminder calendar to avoid forgetfulness effective?].
AB  - OBJECTIVE: To analyse the efficacy of the intervention with a calendar reminder
      of the medication taking in the treatment of the hyperlipidemias. DESIGN:
      Controlled, randomised clinical trial. SETTING: Twelve clinics at 5 primary care
      centres, Spain. PARTICIPANTS: Two hundred and twenty people diagnosed with
      hypercholesterolaemia according to Spanish Consensus criteria were chosen.
      INTERVENTION: Two groups were formed. The control group (CG) of 110 patients, who
      received the doctor's normal treatment; and the Intervention group (IG) of 110
      patients, who received in addition a calendar remider of medication taking. MAIN
      MEASUREMENTS: Meausured of compliance was performed by moniotrs electronic (MEMS)
      and cholesterol, triglycerides, HDL-C, and LDL-C determined at the start, and at
      the third and sixth months. Percentages of patients complying (80%-110%), the
      mean compliance percentage and the degree of control were compared. The reduction
      of absolute and relative risk (RAR and RRR) and the mean number of people that
      required an intervention in order to avoid non-compliance (NI) were calculated.
      RESULTS: One hundred and eighty eight people (85.45%) completed the survey, 96 in
      the IG and 92 in the CG; 26.55% were non compliers with the therapy (CI, +/-6.3%)
      (IG, 10.5%, CI, +/-4.6%; CG, 42.6%, CI, +/-10.1% [P<.0001]). Mean compliance ran
      at 88,1% (IC, +/-4.6%) overall, at 92% (CI, +/-5.4%) in the IG and at 84% (CI, +/
      7.4%) in the IG (P<.05). The RAR was 32.1%, the RRR 75.35%, and the NI was 3.1
      patients. The patients with cholesterol controlled ran at 66.7% (CI, +/-9.4%) in
      the IG and 41.2% in the CG (P<.001). CONCLUSIONS: The calendar reminder
      intervention is an efficacious way of improving the percentage of patients
      complying with lipaemia treatment.

PMID- 18093506
TI  - [Health workers, their migration and its consequences].

PMID- 18093507
TI  - [Treatment of attention deficit disorder].

PMID- 18093508
TI  - [Are we monitoring, in primary care, dyslipaemia in patients with ischaemic
      cardiopathy?].

PMID- 18093509
TI  - [Immigration-Hypertension SOS?].

PMID- 18093510
TI  - [Spanish primary care doctors and their knowledge of immigration].

PMID- 18093511
TI  - [Is anxiolytic, soporific, and antidepressant medication used properly? A study
      performed in community pharmacies].

PMID- 18093512
TI  - [Educational techniques in the use of bronchial asthma inhalers].

PMID- 18093513
TI  - [Assessment of the approach and training of professionals to improve health-care
      delivery].

PMID- 18093514
TI  - A crystal-clear interaction: relating neuroligin/neurexin complex structure to
      function at the synapse.
AB  - Neuronal circuits are maintained by homeostatic mechanisms controlling synapse
      maturation and signaling. Neuroligins (NLs) and neurexins (Nrxs) may regulate the
      fine balance between excitation and inhibition. In this issue of Neuron, Arac et
      al. and Fabrichny et al. define crystal structures of NLs bound to beta-Nrx,
      providing insights into their synaptic actions and clarifying structural defects
      associated with autism-linked mutations.

PMID- 18093515
TI  - A doubleheader in endocytosis.
AB  - Synaptojanin1 degrades the signaling lipid phosphatidylinositol-4,5-bisphosphate
      and facilitates compensatory endocytosis, clathrin-coat disassembly, and vesicle
      reavailability at active synapses. In this issue of Neuron, Mani et al. provide
      new information about the separate roles of synaptojanin's two phosphatase
      domains and its interactions with endophilin in regulating these important
      aspects of the vesicle cycle.

PMID- 18093516
TI  - Pumping up the synapse.
AB  - Synchronized control of excitatory and inhibitory synapse maturation is crucial
      for normal brain wiring, while its dysfunction leads to neurodevelopmental
      disorders, including autism. A paper in this issue of Neuron identified a novel
      role for the KCC2 pump, also responsible for the GABAergic synapse developmental
      switch, in regulating spiny excitatory synapse maturation, implicating it in the
      coordinated maturation of inhibitory and excitatory synapses.

PMID- 18093517
TI  - Endocannabinoids mediate synaptic plasticity at mixed synapses.
AB  - Endocannabinoids are generally known to suppress excitatory or inhibitory
      synaptic transmission. Now, in an elegant series of experiments, Cachope et al.
      reveal a novel signaling pathway whereby endocannabinoids indirectly potentiate
      mixed chemical and electrical synapses. Gap junction-mediated transmission can
      thus be potentiated via distinct frequency-dependent mechanisms.

PMID- 18093518
TI  - The back and forth of dendritic plasticity.
AB  - Synapses are located throughout the often-elaborate dendritic tree of central
      neurons. Hebbian models of plasticity require temporal association between
      synaptic input and neuronal output to produce long-term potentiation of
      excitatory transmission. Recent studies have highlighted how active dendritic
      spiking mechanisms control this association. Here, we review new work showing
      that associative synaptic plasticity can be generated without neuronal output and
      that the interplay between neuronal architecture and the active electrical
      properties of the dendritic tree regulates synaptic plasticity.

PMID- 18093519
TI  - Correction of fragile X syndrome in mice.
AB  - Fragile X syndrome (FXS) is the most common form of heritable mental retardation
      and the leading identified cause of autism. FXS is caused by transcriptional
      silencing of the FMR1 gene that encodes the fragile X mental retardation protein
      (FMRP), but the pathogenesis of the disease is unknown. According to one
      proposal, many psychiatric and neurological symptoms of FXS result from unchecked
      activation of mGluR5, a metabotropic glutamate receptor. To test this idea we
      generated Fmr1 mutant mice with a 50% reduction in mGluR5 expression and studied
      a range of phenotypes with relevance to the human disorder. Our results
      demonstrate that mGluR5 contributes significantly to the pathogenesis of the
      disease, a finding that has significant therapeutic implications for fragile X
      and related developmental disorders.

PMID- 18093520
TI  - Knot/Collier and cut control different aspects of dendrite cytoskeleton and
      synergize to define final arbor shape.
AB  - In a complex nervous system, neuronal functional diversity is reflected in the
      wide variety of dendritic arbor shapes. Different neuronal classes are defined by
      class-specific transcription factor combinatorial codes. We show that the
      combination of the transcription factors Knot and Cut is particular to Drosophila
      class IV dendritic arborization (da) neurons. Knot and Cut control different
      aspects of the dendrite cytoskeleton, promoting microtubule- and actin-based
      dendritic arbors, respectively. Knot delineates class IV arbor morphology by
      simultaneously synergizing with Cut to promote complexity and repressing Cut
      mediated promotion of dendritic filopodia/spikes. Knot increases dendritic arbor
      outgrowth through promoting the expression of Spastin, a microtubule-severing
      protein disrupted in autosomal dominant hereditary spastic paraplegia (AD-HSP).
      Knot and Cut may modulate cellular mechanisms that are conserved between
      Drosophila and vertebrates. Hence, this study gives significant general insight
      into how multiple transcription factors combine to control class-specific
      dendritic arbor morphology through controlling different aspects of the
      cytoskeleton.

PMID- 18093521
TI  - Structural analysis of the synaptic protein neuroligin and its beta-neurexin
      complex: determinants for folding and cell adhesion.
AB  - The neuroligins are postsynaptic cell adhesion proteins whose associations with
      presynaptic neurexins participate in synaptogenesis. Mutations in the neuroligin
      and neurexin genes appear to be associated with autism and mental retardation.
      The crystal structure of a neuroligin reveals features not found in its
      catalytically active relatives, such as the fully hydrophobic interface forming
      the functional neuroligin dimer; the conformations of surface loops surrounding
      the vestigial active center; the location of determinants that are critical for
      folding and processing; and the absence of a macromolecular dipole and presence
      of an electronegative, hydrophilic surface for neurexin binding. The structure of
      a beta-neurexin-neuroligin complex reveals the precise orientation of the bound
      neurexin and, despite a limited resolution, provides substantial information on
      the Ca2+-dependent interactions network involved in trans-synaptic neurexin
      neuroligin association. These structures exemplify how an alpha/beta-hydrolase
      fold varies in surface topography to confer adhesion properties and provide
      templates for analyzing abnormal processing or recognition events associated with
      autism.

PMID- 18093522
TI  - Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal
      specific protein-protein and protein-Ca2+ interactions.
AB  - Neurexins and neuroligins provide trans-synaptic connectivity by the Ca2+
      dependent interaction of their alternatively spliced extracellular domains.
      Neuroligins specify synapses in an activity-dependent manner, presumably by
      binding to neurexins. Here, we present the crystal structures of neuroligin-1 in
      isolation and in complex with neurexin-1 beta. Neuroligin-1 forms a constitutive
      dimer, and two neurexin-1 beta monomers bind to two identical surfaces on the
      opposite faces of the neuroligin-1 dimer to form a heterotetramer. The neuroligin
      1/neurexin-1 beta complex exhibits a nanomolar affinity and includes a large
      binding interface that contains bound Ca2+. Alternatively spliced sites in
      neurexin-1 beta and in neuroligin-1 are positioned nearby the binding interface,
      explaining how they regulate the interaction. Structure-based mutations of
      neuroligin-1 at the interface disrupt binding to neurexin-1 beta, but not the
      folding of neuroligin-1 and confirm the validity of the binding interface of the
      neuroligin-1/neurexin-1 beta complex. Our results provide molecular insights for
      understanding the role of cell-adhesion proteins in synapse function.

PMID- 18093523
TI  - The dual phosphatase activity of synaptojanin1 is required for both efficient
      synaptic vesicle endocytosis and reavailability at nerve terminals.
AB  - Phosphoinositides have been implicated in synaptic vesicle recycling largely
      based on studies of enzymes that regulate phosphoinositide synthesis and
      hydrolysis. One such enzyme is synaptojanin1, a multifunctional protein conserved
      from yeast to humans, which contains two phosphoinositol phosphatase domains and
      a proline-rich domain. Genetic ablation of synaptojanin1 leads to pleiotropic
      defects in presynaptic function, including accumulation of free clathrin-coated
      vesicles and delayed vesicle reavailability, implicating this enzyme in
      postendocytic uncoating of vesicles. To further elucidate the role of
      synaptojanin1 at nerve terminals, we performed quantitative synaptic vesicle
      recycling assays in synj1(-/-) neurons. Our studies show that synaptojanin1 is
      also required for normal vesicle endocytosis. Defects in both endocytosis and
      postendocytic vesicle reavailability can be fully restored upon reintroduction of
      synaptojanin1. However, expression of synaptojanin1 with mutations abolishing
      catalytic activity of each phosphatase domain reveals that the dual action of
      both domains is required for normal synaptic vesicle internalization and
      reavailability.

PMID- 18093524
TI  - KCC2 interacts with the dendritic cytoskeleton to promote spine development.
AB  - The neuron-specific K-Cl cotransporter, KCC2, induces a developmental shift to
      render GABAergic transmission from depolarizing to hyperpolarizing. Now we
      demonstrate that KCC2, independently of its Cl(-) transport function, is a key
      factor in the maturation of dendritic spines. This morphogenic role of KCC2 in
      the development of excitatory synapses is mediated by structural interactions
      between KCC2 and the spine cytoskeleton. Here, the binding of KCC2 C-terminal
      domain to the cytoskeleton-associated protein 4.1N may play an important role. A
      more general conclusion based on our data is that KCC2 acts as a synchronizing
      factor in the functional development of glutamatergic and GABAergic synapses in
      cortical neurons and networks.

PMID- 18093526
TI  - Release-dependent variations in synaptic latency: a putative code for short- and
      long-term synaptic dynamics.
AB  - In the cortex, synaptic latencies display small variations ( approximately 1-2
      ms) that are generally considered to be negligible. We show here that the
      synaptic latency at monosynaptically connected pairs of L5 and CA3 pyramidal
      neurons is determined by the presynaptic release probability (Pr): synaptic
      latency being inversely correlated with the amplitude of the postsynaptic current
      and sensitive to manipulations of Pr. Changes in synaptic latency were also
      observed when Pr was physiologically regulated in short- and long-term synaptic
      plasticity. Paired-pulse depression and facilitation were respectively associated
      with increased and decreased synaptic latencies. Similarly, latencies were
      prolonged following induction of presynaptic LTD and reduced after LTP induction.
      We show using the dynamic-clamp technique that the observed covariation in
      latency and synaptic strength is a synergistic combination that significantly
      affects postsynaptic spiking. In conclusion, amplitude-related variation in
      latency represents a putative code for short- and long-term synaptic dynamics in
      cortical networks.

PMID- 18093525
TI  - Potentiation of electrical and chemical synaptic transmission mediated by
      endocannabinoids.
AB  - Endocannabinoids are well established as inhibitors of chemical synaptic
      transmission via presynaptic activation of the cannabinoid type 1 receptor
      (CB1R). Contrasting this notion, we show that dendritic release of
      endocannabinoids mediates potentiation of synaptic transmission at mixed
      (electrical and chemical) synaptic contacts on the goldfish Mauthner cell.
      Remarkably, the observed enhancement was not restricted to the glutamatergic
      component of the synaptic response but also included a parallel increase in
      electrical transmission. This effect involved the activation of CB1 receptors and
      was indirectly mediated via the release of dopamine from nearby varicosities,
      which in turn led to potentiation of the synaptic response via a cAMP-dependent
      protein kinase-mediated postsynaptic mechanism. Thus, endocannabinoid release can
      potentiate synaptic transmission, and its functional roles include the regulation
      of gap junction-mediated electrical synapses. Similar interactions between
      endocannabinoid and dopaminergic systems may be widespread and potentially
      relevant for the motor and rewarding effects of cannabis derivatives.

PMID- 18093527
TI  - Long-term potentiation in rat hippocampal neurons is accompanied by spatially
      widespread changes in intrinsic oscillatory dynamics and excitability.
AB  - Oscillations in neural activity are a prominent feature of many brain states.
      Individual hippocampal neurons exhibit intrinsic membrane potential oscillations
      and intrinsic resonance in the theta frequency range. We found that the
      subthreshold resonance frequency of CA1 pyramidal neurons was location dependent,
      varying more than 3-fold between the soma and the distal dendrites. Furthermore,
      activity- and NMDA-receptor-dependent long-term plasticity increased this
      resonance frequency through changes in h channel properties. The increase in
      resonance frequency and an associated reduction in excitability were nearly
      identical in the soma and the first 300 mum of the apical dendrites. These
      spatially widespread changes accompanying long-term synaptic potentiation also
      reduced the neuron's ability to elicit spikes evoked through a nonpotentiated
      synaptic pathway. Our results suggest that the frequency response of these
      neurons depends on the dendritic location of their inputs and that activity can
      regulate their response dynamics within an oscillating neural network.

PMID- 18093528
TI  - HCN1 channels constrain synaptically evoked Ca2+ spikes in distal dendrites of
      CA1 pyramidal neurons.
AB  - HCN1 hyperpolarization-activated cation channels act as an inhibitory constraint
      of both spatial learning and synaptic integration and long-term plasticity in the
      distal dendrites of hippocampal CA1 pyramidal neurons. However, as HCN1 channels
      provide an excitatory current, the mechanism of their inhibitory action remains
      unclear. Here we report that HCN1 channels also constrain CA1 distal dendritic
      Ca2+ spikes, which have been implicated in the induction of LTP at distal
      excitatory synapses. Our experimental and computational results indicate that
      HCN1 channels provide both an active shunt conductance that decreases the
      temporal integration of distal EPSPs and a tonic depolarizing current that
      increases resting inactivation of T-type and N-type voltage-gated Ca2+ channels,
      which contribute to the Ca2+ spikes. This dual mechanism may provide a general
      means by which HCN channels regulate dendritic excitability.

PMID- 18093529
TI  - GABAA receptor RDL inhibits Drosophila olfactory associative learning.
AB  - In both mammals and insects, neurons involved in learning are strongly modulated
      by the inhibitory neurotransmitter GABA. The GABAA receptor, resistance to
      dieldrin (Rdl), is highly expressed in the Drosophila mushroom bodies (MBs), a
      group of neurons playing essential roles in insect olfactory learning. Flies with
      increased or decreased expression of Rdl in the MBs were generated. Olfactory
      associative learning tests showed that Rdl overexpression impaired memory
      acquisition but not memory stability. This learning defect was due to disrupting
      the physiological state of the adult MB neurons rather than causing developmental
      abnormalities. Remarkably, Rdl knockdown enhanced memory acquisition but not
      memory stability. Functional cellular imaging experiments showed that Rdl
      overexpression abolished the normal calcium responses of the MBs to odors while
      Rdl knockdown increased these responses. Together, these data suggest that RDL
      negatively modulates olfactory associative learning, possibly by gating the input
      of olfactory information into the MBs.

PMID- 18093530
TI  - Developmental switch in neuropeptide Y and melanocortin effects in the
      paraventricular nucleus of the hypothalamus.
AB  - Homeostatic regulation of energy balance in rodents changes dramatically during
      the first 3 postnatal weeks. Neuropeptide Y (NPY) and melanocortin neurons in the
      arcuate nucleus, a primary energy homeostatic center in adults, do not fully
      innervate the paraventricular nucleus (PVN) until the third postnatal week. We
      have identified two classes of PVN neurons responsive to these neuropeptides,
      tonically firing neurosecretory (NS) and burst-firing preautonomic (PA) cells. In
      neonates, NPY could inhibit GABAergic inputs to nearly all NS and PA neurons,
      while melanocortin regulation was minimal. However, there was a dramatic, age
      dependent decrease in NPY responses specifically in the PA neurons, and a 3-fold
      increase in melanocortin responses in NS cells. These age-dependent changes were
      accompanied by changes in spontaneous GABAergic currents onto these neurons. This
      primarily NPYergic regulation in the neonates likely promotes the positive energy
      balance necessary for growth, while the developmental switch correlates with
      maturation of homeostatic regulation of energy balance.

PMID- 18093532
TI  - Endogenous cortical rhythms determine cerebral specialization for speech
      perception and production.
AB  - Across multiple timescales, acoustic regularities of speech match rhythmic
      properties of both the auditory and motor systems. Syllabic rate corresponds to
      natural jaw-associated oscillatory rhythms, and phonemic length could reflect
      endogenous oscillatory auditory cortical properties. Hemispheric lateralization
      for speech could result from an asymmetry of cortical tuning, with left and right
      auditory areas differentially sensitive to spectro-temporal features of speech.
      Using simultaneous electroencephalographic (EEG) and functional magnetic
      resonance imaging (fMRI) recordings from humans, we show that spontaneous EEG
      power variations within the gamma range (phonemic rate) correlate best with left
      auditory cortical synaptic activity, while fluctuations within the theta range
      correlate best with that in the right. Power fluctuations in both ranges
      correlate with activity in the mouth premotor region, indicating coupling between
      temporal properties of speech perception and production. These data show that
      endogenous cortical rhythms provide temporal and spatial constraints on the
      neuronal mechanisms underlying speech perception and production.

PMID- 18093531
TI  - Abstract coding of audiovisual speech: beyond sensory representation.
AB  - Is there a neural representation of speech that transcends its sensory
      properties? Using fMRI, we investigated whether there are brain areas where
      neural activity during observation of sublexical audiovisual input corresponds to
      a listener's speech percept (what is "heard") independent of the sensory
      properties of the input. A target audiovisual stimulus was preceded by stimuli
      that (1) shared the target's auditory features (auditory overlap), (2) shared the
      target's visual features (visual overlap), or (3) shared neither the target's
      auditory or visual features but were perceived as the target (perceptual
      overlap). In two left-hemisphere regions (pars opercularis, planum polare), the
      target invoked less activity when it was preceded by the perceptually overlapping
      stimulus than when preceded by stimuli that shared one of its sensory components.
      This pattern of neural facilitation indicates that these regions code sublexical
      speech at an abstract level corresponding to that of the speech percept.

PMID- 18093533
TI  - MicroRNA-155 function in B Cells.
AB  - Vigorito et al. (2007) report (in this issue of Immunity) that B cells require
      microRNA (miR)-155 for normal production of isotype-switched, high-affinity
      antibodies and for a memory response. They identify transcriptional regulator
      Pu.1 as a functionally important target of miR-155 in B cells.

PMID- 18093534
TI  - E proteins enforce security checkpoints in the thymus.
AB  - In this issue of Immunity, two studies define new roles for E proteins in
      thymocyte development. Agata et al. (2007) show a new role in beta selection;
      Jones and Zhuang (2007) demonstrate a role in positive selection.

PMID- 18093535
TI  - Apoptotic PS to phagocyte TIM-4: eat me.
AB  - Although cells dying by apoptosis expose the classical "eat me" signal
      phosphatidylserine (PS), a phagocytic transmembrane receptor for PS has proved
      elusive. Now cell and structural studies (Kobayashi et al. [2007] and Santiago et
      al. [2007] in this issue of Immunity) implicate the type I molecule TIM-4.

PMID- 18093536
TI  - Protection one cell thick.
AB  - Specific immunity is a layer of defense exquisitely broad, terrifyingly thin, and
      yet remarkably durable on challenge. In this issue of Immunity, Stemberger et al.
      (2007) now take this concept to its logical extreme by offering evidence that
      expenditure of a single lymphocyte yields its own replenishment.

PMID- 18093537
TI  - Human primary immunodeficiency diseases.
AB  - Primary immunodeficiency diseases (PID) provide invaluable insight into immune
      system, notably in vivo immune responses to microorganisms as based on the
      variable vulnerability to pathogens and opportunistic agents. PID are also very
      informative in defining key checkpoints controlling immunity to self. Despite a
      Mendelian inheritance of most PID, mutations of a given gene can lead to a vast
      array of phenotypes as a function of the type of mutations, environmental
      factors, the occurrence of additional somatic mutations, or regulatory factors,
      which add considerable but hitherto underestimated complexity. Understanding the
      molecular pathophysiology of PID is not only contributing to a better knowledge
      of the immune system but may also favor new therapeutic approaches.

PMID- 18093538
TI  - Acquisition of a functional T cell receptor during T lymphocyte development is
      enforced by HEB and E2A transcription factors.
AB  - The T cell receptor (TCR) is required for positive selection and the subsequent
      transition from the CD4(+)CD8(+) double-positive (DP) to the CD4(+) or CD8(+)
      single-positive (SP) stage of alphabeta T cell development. The molecular
      mechanism that maintains DP fate prior to the acquisition of a functional TCR is
      not clear. We have shown here that the structurally and functionally related
      transcription factors HEB and E2A work together to maintain DP fate and to
      control the DP to SP transition. Simultaneous deletion of HEB and E2A in DP
      thymocytes was sufficient for DP to SP transition independent of TCR. Loss of HEB
      and E2A allowed DP cells to bypass the requirement for TCR-mediated positive
      selection, downregulate DP-associated genes, and upregulate SP-specific genes.
      These results identify HEB and E2A as the gatekeepers that maintain cells at the
      DP stage of development until a functional alphabetaTCR is produced.

PMID- 18093539
TI  - Regulation of T cell receptor beta gene rearrangements and allelic exclusion by
      the helix-loop-helix protein, E47.
AB  - Allelic exclusion of antigen-receptor genes is ensured primarily by monoallelic
      locus activation upon rearrangement and subsequently by feedback inhibition of
      continued rearrangement. Here, we demonstrated that the basic helix-loop-helix
      protein, E47, promoted T cell receptor beta (TCRbeta) gene rearrangement by
      directly binding to target gene segments to increase chromatin accessibility in a
      dosage-sensitive manner. Feedback signaling abrogated E47 binding, leading to a
      decline in accessibility. Conversely, enforced expression of E47 induced TCRbeta
      gene rearrangement by antagonizing feedback inhibition. Thus, the abundance of
      E47 is rate limiting in locus activation, and feedback signaling downregulates
      E47 activity to ensure allelic exclusion.

PMID- 18093540
TI  - Opposing functions of the T cell receptor kinase ZAP-70 in immunity and tolerance
      differentially titrate in response to nucleotide substitutions.
AB  - Null mutations that cripple T cell receptor (TCR) signaling explain rare primary
      immunodeficiencies, but it is not understood why more common polymorphisms that
      lead to subtle TCR signaling defects are paradoxically associated with
      autoimmunity. Here we analyzed how a series of Zap70 variants with step-wise
      decreases in TCR signaling impacted upon opposing TCR functions of immunity and
      tolerance. One Zap70 variant, murdock, moderately decreased TCR signaling and
      thymic selection without compromising immunological tolerance, whereas a more
      severe Zap70 defect, mrtless, abolished thymic-positive selection and led to
      immunodeficiency. Signaling capacities between these two thresholds
      disproportionately compromised negative selection and Foxp3(+) regulatory T cell
      formation, creating a cellular imbalance between immunogenic and tolerogenic
      functions that resulted in the excessive production of autoantibodies and
      immunoglobulin E (IgE). The pleiotropic functions of ZAP-70 and their
      differential response to graded variation provide a paradigm for understanding
      the complex outcomes of human genetic variation.

PMID- 18093541
TI  - Interleukin-10 expression in macrophages during phagocytosis of apoptotic cells
      is mediated by homeodomain proteins Pbx1 and Prep-1.
AB  - Production of interleukin (IL)-10, a major immunoregulatory cytokine, by
      phagocytes during clearance of apoptotic cells is critical to ensuring cellular
      homeostasis and suppression of autoimmunity. Little is known about the regulatory
      mechanisms in this fundamental process. We report that IL-10 production
      stimulated by apoptotic cells was regulated at the point of transcription in a
      manner dependent on p38 mitogen-activated protein kinase, partially on the
      scavenger receptor CD36, and required cell-cell contact but not phagocytosis. By
      using a reporter assay, we mapped the apoptotic-cell-response element (ACRE) in
      the human IL10 promoter and provide biochemical and physiological evidence that
      ACRE mediates the transcriptional activation of IL10 by pre-B cell leukemia
      transcription factor-1b and another Hox cofactor Pbx-regulating protein 1 in
      response to apoptotic cells. This study establishes a role of two developmentally
      critical factors (Pbx1 and Prep-1) in the regulation of homeostasis in the immune
      system.

PMID- 18093542
TI  - Cryoglobulins as indicators of upregulated immune response in schizophrenia.
AB  - OBJECTIVE: In the present work the concentration of abnormal immune complexes,
      cryoglobulins (Cgs), in the blood of schizophrenic patients was determined, and
      immunochemical composition of these complexes was studied. PATIENTS AND METHODS:
      Eighty multiple-episode schizophrenia-affected subjects (55 medicated, 25 drug
      free) and 40 healthy controls were involved in the study. Cgs were isolated by
      exposure of blood serum samples to precipitation at low temperature followed by
      extensive washings of Cg-enriched pellets. The immunochemical composition of Cgs
      was analyzed using different electrophoretic and immunoblotting systems. RESULTS:
      Significantly increased blood serum levels of type III Cgs were detected in all
      schizophrenia-affected subjects, as compared to controls. We also revealed the
      presence of C1q and C3 complement proteins and their activation products in Cgs
      isolated from the blood of schizophrenic patients. CONCLUSIONS: The results of
      the present study suggest that Cgs are involved in schizophrenia-associated
      upregulated immune response by binding the complement proteins, activating the
      complement cascade and triggering aberrant apoptosis.

PMID- 18093543
TI  - The human PDI family: versatility packed into a single fold.
AB  - The enzymes of the protein disulfide isomerase (PDI) family are thiol-disulfide
      oxidoreductases of the endoplasmic reticulum (ER). They contain a CXXC active
      site sequence where the two cysteines catalyze the exchange of a disulfide bond
      with or within substrates. The primary function of the PDIs in promoting
      oxidative protein folding in the ER has been extended in recent years to include
      roles in other processes such as ER-associated degradation (ERAD), trafficking,
      calcium homeostasis, antigen presentation and virus entry. Some of these
      functions are performed by non-catalytic members of the family that lack the
      active-site cysteines. Regardless of their function, all human PDIs contain at
      least one domain of approximately 100 amino acid residues with structural
      homology to thioredoxin. As we learn more about the individual proteins of the
      family, a complex picture is emerging that emphasizes as much their differences
      as their similarities, and underlines the versatility of the thioredoxin fold.
      Here, we primarily explore the diversity of cellular functions described for the
      human PDIs.

PMID- 18093544
TI  - Grand Challenges to reduce stroke.

PMID- 18093545
TI  - Alzheimer's disease: advances in trafficking.

PMID- 18093546
TI  - MS: prevention of neural damage by early intervention.

PMID- 18093547
TI  - Stroke: encouragement and disappointment in clinical trials.

PMID- 18093548
TI  - Epilepsy: randomised trials and genetic tribulations.

PMID- 18093549
TI  - Parkinson's disease and movement disorders: moving forward.

PMID- 18093550
TI  - Headache: new concepts, models, and treatments.

PMID- 18093551
TI  - Neuromuscular diseases: therapeutic advances.

PMID- 18093552
TI  - Neuro-oncology: new insights and advances in treatment.

PMID- 18093553
TI  - Paediatric neurology: traditional opinions revisited.

PMID- 18093554
TI  - CNS infections: progress in therapy, diagnosis, and prevention.

PMID- 18093555
TI  - Brain screening and incidental findings: flocking to folly?

PMID- 18093557
TI  - Lyme neuroborreliosis in Great Britain.

PMID- 18093559
TI  - Alzheimer's disease funding and the French health system.

PMID- 18093560
TI  - Massimo Filippi: imaging in Italy.

PMID- 18093563
TI  - The medical management of the epilepsies in children: conceptual and practical
      considerations.
AB  - Epilepsy in children encompasses several syndromes. The cardinal feature of these
      syndromes is a predisposition to epileptic seizures but each is associated with
      different prognoses. The goals of treatment will clearly differ between children
      who become seizure-free on antiepileptic drug (AED) treatment and those children
      with refractory epilepsy. Treatment should be tailored to the needs of the
      patient, with a comprehensive approach that addresses the common additional
      morbidities in children with epilepsy. In this Review, we present an overview of
      the medical management of epilepsy in children and discuss the dilemmas of
      everyday practice, such as selection of AED, assessment of outcome, monitoring of
      treatment, and the decision to withdraw medication when the child is free from
      seizures. Furthermore, we emphasise the need to establish rational goals for
      treatment, such as aiming for the best possible quality of life rather than
      freedom from seizures at all costs.

PMID- 18093564
TI  - Tension-type headache: current research and clinical management.
AB  - Tension-type headache (TTH) is the most common form of headache, and chronic
      tension-type headache (CTTH) is one of the most neglected and difficult types of
      headache to treat. The pathogenesis of TTH is multifactorial and varies between
      forms and individuals. Peripheral mechanisms (myofascial nociception) and central
      mechanisms (sensitisation and inadequate endogenous pain control) are
      intermingled: the former predominate in infrequent and frequent TTH, whereas the
      latter predominate in CTTH. Acute therapy is effective for episodes of TTH,
      whereas preventive treatment--which is indicated for frequent and chronic TTH-
      is, on average, not effective. For most patients with CTTH, the combination of
      drug therapies and non-drug therapies (such as relaxation and stress management
      techniques or physical therapies) is recommended. There is clearly an urgent need
      to improve the management of patients who are disabled by headache. This Review
      summarises the present knowledge on TTH and discusses some of its more
      problematic features.

PMID- 18093565
TI  - Strategies to advance translational research into brain barriers.
AB  - There is a paucity of therapies for most neurological disorders--from rare
      lysosomal storage diseases to major public health concerns such as stroke and
      Alzheimer's disease. Advances in the targeting of drugs to the CNS are essential
      for the future success of neurotherapeutics; however, the delivery of many
      potentially therapeutic and diagnostic compounds to specific areas of the brain
      is restricted by the blood-brain barrier, the blood-CSF barrier, or other
      specialised CNS barriers. These brain barriers are now recognised as a major
      obstacle to the treatment of most brain disorders. The challenge to deliver
      therapies to the CNS is formidable, and the solution will require concerted
      international efforts among academia, government, and industry. At a recent
      meeting of expert panels, essential and high-priority recommendations to propel
      brain barrier research forward in six topical areas were developed and these
      recommendations are presented here.

PMID- 18093566
TI  - Mitochondria in the aetiology and pathogenesis of Parkinson's disease.
AB  - Several biochemical abnormalities have been described in the brains of patients
      with Parkinson's disease (PD), including oxidative stress and mitochondrial
      dysfunction. The identification of specific gene mutations that cause PD has
      reinforced the relevance of oxidative stress and mitochondrial dysfunction in the
      familial and the sporadic forms of the disease. The proteins that are associated
      with familial PD--PTEN-induced putative kinase 1 (PINK1), DJ-1, alpha-synuclein,
      leucine-rich repeat kinase 2, and, possibly, parkin--are either mitochondrial
      proteins or are associated with mitochondria, and all interface with the pathways
      of oxidative stress and free radical damage. Insights into the aetiology and
      pathogenesis of PD provide hope that drugs or cocktails of drugs that might
      successfully intervene in the pathogenesis and slow the progression of the
      disease can be derived from the study of the converging rather than diverging
      pathways to cell dysfunction and death.

PMID- 18093567
TI  - Recurrent reversible coma in an adolescent.

PMID- 18093568
TI  - Rattus norvegicus as a model for persistent renal colonization by pathogenic
      Leptospira interrogans.
AB  - Leptospirosis continues to be a disease with a poorly understood pathogenesis.
      The experimental rat model is amenable for the investigation of leptospiral
      dissemination, tropism, persistence of renal colonization and factors related to
      disease resistance. In this study, Wistar rats were infected intraperitoneally
      with virulent Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130.
      The detection of leptospires in tissue samples was based on culture, silver
      staining and immunofluorescence techniques. An inoculum of 10,000 leptospires
      induced colonization in 50% of rats and colonization persisted for the 4-month
      period of the study. Dissemination kinetics revealed that renal colonization took
      place 7-9 days after infection, with no underlying histopathology. The peak
      leptospiral load occurred on day 5 post-infection, followed by rapid clearance in
      all tissues except the kidneys, where dense leptospiral aggregates persisted in
      the renal tubules. We conclude that the experimental rat model is suitable for
      studies contributing towards the understanding of the mechanisms of colonization
      and resistance to severe disease in leptospirosis.

PMID- 18093569
TI  - Experimental toxocariosis in BALB/c mice: effect of the inoculation dose on brain
      and eye involvement.
AB  - Ocular toxocarosis (OT) is a well-established disease. However, our understanding
      of the migratory route, time and circumstances that produce ocular invasion are
      not clear. To improve our knowledge of factors related to ocular invasion, BALB/c
      mice were inoculated with simple doses (SD) of 6, 12, 50, 100, 200 and 1000
      embryonated eggs (EE) and multiple doses (MD) of 200 and 1000 EE. Brains and eyes
      were studied for the presence of larvae in animals sacrificed on days 3, 5, 7, 9,
      11, 13, 15, 17, 19, 40, 80 and 120 in SD and on days 28, 30, 32, 34, 36, 38, 40,
      42, 46, 87 and 127 in MD. The humoral immune responses were studied by ELISA
      using excretory-secretory antigen. Due to the considerable number of days tested,
      results showed are based on one set of experiments. However, each point studied
      represents the result obtained from a group of five mice. We have shown that the
      eye involvement with Toxocara canis larvae is a phenomenon mainly produced once
      larvae have reached the brain. There is a direct relationship between the
      parasitic load and the number of ocular larvae. Moreover, the arrival of larvae
      to the eye is an independent event, unrelated to the kind of administered dose
      (SD, MD), although the number of the brain larvae was higher in the cases of MD.
      High levels of specific antibodies were observed but they did not prevent the
      arrival of the larvae to the brain and the eye.

PMID- 18093570
TI  - Tissue reactions to collagen scaffolds in the oral mucosa and skin of rats:
      environmental and mechanical factors.
AB  - OBJECTIVE: To compare the tissue reactions to implanted collagen scaffolds in the
      palate and the skin of rats. DESIGN: Crosslinked collagen scaffolds were
      implanted submucoperiosteally in the palate, and subcutaneously on the skull and
      on the back of 25 rats and evaluated after up to 16 weeks. On H&E-stained
      sections, the cell density and the number of giant cells within the scaffolds
      were determined. Blood vessels, inflammatory cells, and myofibroblasts were
      detected by immunohistochemistry. RESULTS: A faster ingrowth of myofibroblasts
      and blood vessels in the palate was found during the first week compared with the
      skin. A more severe inflammatory response was initially found in the back skin.
      Furthermore, about twice as much giant cells were present in these scaffolds.
      CONCLUSION: The oral environment seems to promote the ingrowth of myofibroblasts
      and blood vessels into the scaffolds. Mechanical stimuli seem to enhance the
      initial inflammatory response. Overall, the scaffolds were gradually integrated
      within the host tissue, eliciting only a transient inflammatory response. The
      scaffolds were biocompatible and are promising for future applications in oral
      surgery.

PMID- 18093571
TI  - Effects of bolus size and hardness on within-subject variability of chewing cycle
      kinematics.
AB  - This study analysed how bolus hardness and size affect within-subject variability
      of chewing cycle kinematics. Two independent prospective studies were performed;
      both tracked chin movements using an optoelectronic recording system. Computer
      programs identified each subject's ten most representative cycles, and multilevel
      modelling procedures were used to estimate variances. One study evaluated 38
      subjects who chewed 1, 2, 4 or 8 g of gum presented in random order. The second
      study evaluated 26 subjects who chewed approximately 2.5 g of harder (670 g) or
      softer (440 g) gum, also presented in random order. In terms of bolus size, the
      2g and 1g boluses produced the least and greatest relative within-subject
      variability, respectively; the largest differences were found for cycle duration
      and excursions. Within-subject variability when chewing the harder gum was
      consistently greater than when chewing the softer gum, except for lateral
      movement towards the balancing side. Because bolus hardness and bolus size
      influence within-subject variability differently, they must be taken into
      consideration when designing experiments to study masticatory kinematics. We
      conclude that a 2g bolus of soft gum should be used in studies of chewing cycle
      kinematics in order to reduce within-subject variability and increase statistical
      power.

PMID- 18093572
TI  - Appraisals of obsessional thoughts in normal samples.
AB  - Cognitive theories of obsessive-compulsive disorder (OCD) posit that appraisals
      about the significance of thoughts are critical in the development and
      persistence of obsessions. Rachman [(1997). A cognitive theory of obsessions.
      Behaviour Research and Therapy, 35, 793-802.] proposes that appraisals of
      unwanted thoughts distinguish clinical obsessions from normal intrusive thoughts;
      thoughts appraised as important and personally significant are expected to be
      upsetting and recur. Appraisals are also expected to be related to symptoms of
      OCD. To explore the features of normal appraisals of obsession-like thoughts,
      nonclinical participants in two studies rated the personal significance of
      intrusive thoughts portrayed in vignettes containing prototypical themes
      associated with primary obsessions: aggressive, sexual, and blasphemous thoughts.
      Unwanted intrusive thoughts that were described as occurring more frequently were
      appraised as more personally significant, but participants appraised these
      socially unacceptable thoughts similarly whether they imagined having personally
      experienced them or a friend confiding about having experienced them. Appraisals
      in both studies were related to subclinical OC symptoms and OC beliefs.

PMID- 18093573
TI  - The influence of animal fear on attentional capture by fear-relevant animal
      stimuli in children.
AB  - The present study demonstrated that pictures of fear-relevant animals, snakes and
      spiders, presented among backgrounds of other animal stimuli captured attention
      and interfered in the detection of a neutral target to the same extent in a large
      sample of unselected children (N=81). Moreover, detection of a neutral target
      animal was slowed more in the presence of a feared fear-relevant distracter,
      e.g., a snake for snake fearful children, than in the presence of a not feared
      fear-relevant distracter, e.g., a spider for snake fearful children. These
      results indicate attentional capture by phylogenetically fear-relevant animal
      stimuli in children and the selective enhancement of this effect by fear of these
      animals. These findings are consistent with current models of preferential
      processing of phylogenetically prepared threat stimuli and with cognitive models
      of anxiety that propose an enhancing effect of fear in the processing of fear
      related stimuli.

PMID- 18093574
TI  - Potassium channels in hippocampal neurones are absent in a transgenic but not in
      a chemical model of Alzheimer's disease.
AB  - We have investigated using single channel patch-clamp methods potassium channel
      prevalence in hippocampal neurones from two animal models of AD. Experiments have
      been carried out on transgenic mice (Tg2576) carrying the Swedish mutation
      (K670N/M671L) and rats receiving ventricular infusions of okadaic acid. In cell
      attached patches from hippocampal neurones from the Tg2576 and control littermate
      mice there were three principal unitary conductance - 22 pS, 111 pS and 178 pS.
      The two channels of intermediate and large conductance were voltage-dependent,
      highly active in cell-attached patches, activity decreasing markedly on
      hyperpolarisation. The large conductance channel was sensitive to TEA,
      iberiotoxin, was activated in excised inside-out patches by Ca 2+(i) and is the
      type I maxi-K+ channel. Significantly, there was a reduction in the prevalence of
      a TEA-sensitive 113 pS channel in neurones from TG2576 mice with a corresponding
      increase in prevalence of the maxi-K+ channel. There was no difference in the
      characteristics of maxi-K+ between patches in neurones from the transgenic and
      littermate controls. In the rat model single channel analysis was performed on
      hippocampal neurons from three groups of animals i.e. non-operated, and these
      receiving an infusion of vehicle or vehicle with okadaic acid. Three principal
      unitary conductances of around 18 pS, 118 pS and 185 pS were also observed in
      cell-attached recordings from these three groups. The intermediate and high
      conductance channels were blocked by TEA or 4-AP or 140 mM RbCl. There were no
      statistically significant differences in the channel prevalence or channel
      density between the control and test groups.

PMID- 18093575
TI  - Splenectomy does not interfere with immune response to Leishmania major infection
      in mice.
AB  - Spleen is one of the largest lymphoid organs in the body; it harbors immune cells
      including antigen presenting cells, B and T lymphocytes. It has an important role
      in humoral and cellular immune responses. Herein we investigated the role of
      spleen in the immune response to experimental Leishmania major infection. It is
      known that C57BL/6 mice are resistant to L. major infection whereas BALB/c mice
      are susceptible. Although splenectomy was associated with reduced serum levels of
      IFN-gamma, absence of the spleen did not change the profile of L. major infection
      in the resistant C57BL/6 and BALB/c susceptible mice. Both strains of mice
      maintained the same profile of cytokine production in regional lymph nodes after
      splenectomy and responded in the same way against the infection. Only
      splenectomized BALB/c mice had a reduction in IL-4 and IL-10 production by lymph
      node cells early in infection. Our data suggest that, in localized infections,
      regional lymph nodes may replace efficiently the immunological role of spleen in
      the cellular and humoral immune responses.

PMID- 18093576
TI  - Inhibition of benzopyrene diol epoxide-induced apoptosis by cadmium(II) is AP-1
      independent: role of extracelluler signal related kinase.
AB  - Cadmium, a major metal constituent of tobacco smoke, elicits synergistic
      enhancement of cell transformation when combined with benzo[a]pyrene (BP) or
      other PAHs. The mechanism underlying this synergism is not clearly understood. We
      observed that (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), an ultimate
      carcinogen of BP, induces apoptosis in promotion sensitive mouse epidermal JB6
      Cl41 cells at non-cytotoxic concentrations. BPDE also activates AP-1 several
      folds in AP-1 reporter JB6 cells. Cadmium at non-cytotoxic concentrations
      inhibits both AP-1 activation and apoptosis in response to BPDE. Since AP-1 is
      known to be involved in stress-induced apoptosis we investigated whether
      inhibition of AP-1 by cadmium has any role in the inhibition of BPDE-induced
      apoptosis. MAP kinases (particularly ERKs, p38 and JNKs) are known to have
      important role in DNA damage-induced AP-1 activation. We observed that ERK and
      JNK, but not p38 MAP kinase, are involved in BPDE-induced AP-1 activation. Effect
      of cadmium on MAP kinases and the effect of inhibition of above three MAP kinases
      on BPDE-induced AP-1 activation and apoptosis indicate that AP-1 is probably not
      involved in BPDE-induced apoptosis. Cadmium up-regulates BPDE-activated ERKs and
      ERK inhibition by U0126 relieves cadmium-mediated inhibition of BPDE-induced
      apoptosis. We suggest that cadmium inhibits BPDE-induced apoptosis not involving
      AP-1 but probably through a different mechanism by up-regulating ERK which is
      known to promote cell survival.

PMID- 18093577
TI  - Inhibition of high glucose-induced erythrocyte phosphatidylserine exposure by
      leupeptin and disaccharides.
AB  - High glucose can lead to serious phosphatidylserine exposure of erythrocytes
      which may influence the protective effect of glucose on lyophilization of
      erythrocytes. In this study, caspase activation has not occurred during
      phosphatidylserine exposure of erythrocytes. However, leupeptin can efficiently
      inhibit phosphatidylserine exposure of erythrocytes induced by high glucose. With
      increase of the leupeptin concentrations, the percentages of cells with exposed
      phosphatidylserine were decreased steadily. In addition, trehalose and sucrose
      can significantly inhibit phosphatidylserine exposure and cell shrinkage of
      erythrocytes induced by high glucose through increasing tolerance to osmotic
      shock. When the disaccharide concentrations were more than 100 mM, the
      percentages of cells with exposed phosphatidylserine were similar to those of
      control cells. Moreover, addition of disaccharides in the glucose buffer can
      result in high osmotic pressure which may facilitate uptake of glucose and
      disaccharides into erythrocytes and higher cellular glucose and disaccharide
      concentrations can provide more protection for lyophilized erythrocytes. Although
      disaccharides can increase the osmotolerance and decrease the phosphatidylserine
      exposure of erythrocytes exposed to high glucose, whether disaccharides can
      prevent phosphatidylserine exposure of lyophilized erythrocytes still needs
      further researches.

PMID- 18093578
TI  - Vitrification of rabbit tissues with propylene glycol and trehalose.
AB  - A previous study had suggested the use of a mixture of propanediol and trehalose
      for the preservation of tissues by vitrification. In this paper, we describe
      experiments in which stepwise procedures were developed for adding these
      cryoprotectants to high final concentrations in two rabbit tissues-carotid artery
      and cornea. The tissue concentration of the additives was measured at the end of
      each step so that the temperature of the next step could be chosen to reduce
      toxicity but avoid freezing. This process was arrested when a concentration had
      been reached that should permit vitrification if the tissues were cooled rapidly
      to -175 degrees C. They were stored at that temperature; warmed rapidly by
      conduction; the cryoprotectants removed by stepwise dilution; and appropriate
      active functions measured. These were contraction and relaxation for arteries and
      endothelial integrity and ability to control stromal swelling for the corneas. In
      control experiments the exposure and functional assays were carried out without
      vitrification. It was shown that the tissue concentration of propanediol was
      33%w/w in artery and 30% in cornea. These permitted cooling to -175 degrees C
      without freezing but devitrification occurred during the warming of the arteries,
      though not of the corneas, despite the lower tissue concentration reached in the
      cornea. The function of the vitrified arteries was severely reduced but the
      endothelium of the corneas was substantially intact although we were unable to
      demonstrate any ability to control stromal swelling during normothermic
      perfusion. It appears that concentrations of cryoprotectants sufficient to
      prevent freezing in these tissues during cooling were well tolerated so long as
      appropriate stepwise means of addition and removal were used. Devitrification
      during warming remained a major problem with arteries, but not with corneas. We
      suggest that the composition of the aqueous phase in the tissue with respect to
      components other than the vitrifying agents may be crucial here and that the
      search for agents that will suppress devitrification is an important avenue for
      further study.

PMID- 18093579
TI  - The detached locus encodes Drosophila Dystrophin, which acts with other
      components of the Dystrophin Associated Protein Complex to influence
      intercellular signalling in developing wing veins.
AB  - Dystrophin and Dystroglycan are the two central components of the multimeric
      Dystrophin Associated Protein Complex, or DAPC, that is thought to provide a
      mechanical link between the extracellular matrix and the actin cytoskeleton,
      disruption of which leads to muscular dystrophy in humans. We present the
      characterization of the Drosophila 'crossveinless' mutation detached (det), and
      show that the gene encodes the fly ortholog of Dystrophin. Our genetic analysis
      shows that, in flies, Dystrophin is a non-essential gene, and the sole overt
      morphological defect associated with null mutations in the locus is the variable
      loss of the posterior crossvein that has been described for alleles of det. Null
      mutations in Drosophila Dystroglycan (Dg) are similarly viable and exhibit this
      crossvein defect, indicating that both of the central DAPC components have been
      co-opted for this atypical function of the complex. In the developing wing, the
      Drosophila DAPC affects the intercellular signalling pathways involved in vein
      specification. In det and Dg mutant wings, the early BMP signalling that
      initiates crossvein specification is not maintained, particularly in the pro-vein
      territories adjacent to the longitudinal veins, and this results in the
      production of a crossvein fragment in the intervein between the two longitudinal
      veins. Genetic interaction studies suggest that the DAPC may exert this effect
      indirectly by down-regulating Notch signalling in pro-vein territories, leading
      to enhanced BMP signalling in the intervein by diffusion of BMP ligands from the
      longitudinal veins.

PMID- 18093580
TI  - Associations between grass and weed pollen and emergency department visits for
      asthma among children in Montreal.
AB  - CONTEXT AND OBJECTIVE: Asthma among children is a major public health problem
      worldwide. There are increasing number of studies suggesting a possible
      association between allergenic pollen and exacerbations of asthma. In the context
      of global climate change, a number of future climate and air pollution scenarios
      predict increases in concentrations of pollen, an extension of the pollen season,
      and an increase in the allergenicity of pollen. The goal of the present study is
      to evaluate the short-term effects of exposure to grass and weed pollen on
      emergency department visits and readmissions for asthma among children aged 0-9
      years living in Montreal between April and October, 1994-2004. METHODOLOGY AND
      RESULTS: Time-series analyses were carried out using parametric log-linear
      overdispersed Poisson models that were adjusted for temporal variations, daily
      weather conditions (temperature, atmospheric pressure), and gaseous air
      pollutants (ozone and nitrogen dioxide). We have found positive associations
      between emergency department visits and concentrations of grass pollen 3 days
      after exposure. The effect of grass pollen was higher on emergency department
      readmissions as compared to initial visits. Weak negative associations were found
      between weed pollen (including ragweed pollen) and emergency department visits 2
      days after exposure. CONCLUSION: The data indicate that among children, emergency
      department visits increased with increasing concentrations of grass pollen.

PMID- 18093581
TI  - Actinonin, a meprin inhibitor, protects ischemic acute kidney injury in male but
      not in female rats.
AB  - We investigated the effects of actinonin, an inhibitor of a matrix-degrading
      enzyme meprin, on ischemic acute kidney injury in male and female rats, and these
      were compared with the effects of verapamil, a Ca(2+) channel blocker. Ischemic
      acute kidney injury was induced by occlusion of the left renal artery and vein
      for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. At
      24 h after reperfusion, renal function and histology of both males and females
      showed significant deterioration. The degrees of renal dysfunction and
      histological damage were much more severe in males than in females. Pre-ischemic
      treatment with actinonin (10 or 30 mg/kg, i.v.) dose-dependently attenuated the
      ischemia/reperfusion-induced renal injury in male rats, but failed to improve the
      renal injury in female rats. On the other hand, verapamil (1 mg/kg, i.v.) could
      efficiently prevent the ischemic acute kidney injury in female rats, as well as
      male rats. These results indicate that the renoprotective effect of actinonin is
      male-specific, thereby suggesting that meprin is involved in exacerbation of
      ischemia/reperfusion-induced renal injury in male rats. The possibility that
      meprin is a key factor involved in the sex difference in the pathogenesis of
      ischemic acute kidney injury, warrants further attention.

PMID- 18093582
TI  - Antioxidant and prooxidant properties of ascorbic acid on hepatic dysfunction
      induced by cold ischemia/reperfusion.
AB  - Oxidative stress, which has been generated during reperfusion after a liver
      transplant, has been implicated in the higher rates of postoperative organ
      dysfunction. The aim of this study was to examine the effect of ascorbic acid on
      reperfusion injury after hepatic cold preservation. Isolated perfused rat livers
      were preserved in a University of Wisconsin solution for 30 h at 4 degrees C. The
      bile output was significantly lower after cold ischemia/reperfusion. In contrast,
      the portal pressure, lactate dehydrogenase and purine nucleoside phosphorylase
      activities were elevated by cold ischemia/reperfusion. These changes were
      attenuated at ascorbic acid concentrations of 0.25 and 0.5 mM. However, they were
      augmented at a concentration of 2 mM. Cold ischemia/reperfusion decreased the
      reduced to oxidized glutathione ratio, whereas it increased the level of lipid
      peroxidation and mitochondrial swelling. These changes were prevented exposing
      the liver to 0.5 mM ascorbic acid but were augmented at 2 mM ascorbic acid. These
      results suggest that cold ischemia/reperfusion injury is associated with a higher
      level of oxidative stress and ascorbic acid may act not only as an antioxidant
      but also as a prooxidant during cold ischemia/reperfusion.

PMID- 18093583
TI  - Ozone oxidative preconditioning inhibits inflammation and apoptosis in a rat
      model of renal ischemia/reperfusion injury.
AB  - Ischemia/reperfusion injury, which is commonly seen in the field of renal surgery
      or transplantation, is a major cause of acute renal failure. Previous studies
      showed that ozone oxidative preconditioning (OzoneOP) attenuated renal
      ischemia/reperfusion injury. The objective of this study was to examine the role
      of the OzoneOP in modulating inflammation and apoptosis after renal
      ischemia/reperfusion injury. Rats were subjected to 45 min of renal ischemia,
      with or without treatment with OzoneOP (1 mg/kg). Renal function, inflammation
      and apoptosis were compared at 24 h after renal injury. OzoneOP improved the
      renal dysfunction and reduced inflammation and apoptosis after
      ischemia/reperfusion injury. In conclusion, OzoneOP has potent anti-apoptotic and
      anti-inflammatory properties. These findings may have major implications in the
      treatment of human ischemic acute renal failure.

PMID- 18093584
TI  - Drugs affecting prelamin A processing: effects on heterochromatin organization.
AB  - Increasing interest in drugs acting on prelamin A has derived from the finding of
      prelamin A involvement in severe laminopathies. Amelioration of the nuclear
      morphology by inhibitors of prelamin A farnesylation has been widely reported in
      progeroid laminopathies. We investigated the effects on chromatin organization of
      two drugs inhibiting prelamin A processing by an ultrastructural and biochemical
      approach. The farnesyltransferase inhibitor FTI-277 and the non-peptidomimetic
      drug N-acetyl-S-farnesyl-l-cysteine methylester (AFCMe) were administered to
      cultured control human fibroblasts for 6 or 18 h. FTI-277 interferes with protein
      farnesylation causing accumulation of non-farnesylated prelamin A, while AFCMe
      impairs the last cleavage of the lamin A precursor and is expected to accumulate
      farnesylated prelamin A. FTI-277 caused redistribution of heterochromatin domains
      at the nuclear interior, while AFCMe caused loss of heterochromatin domains,
      increase of nuclear size and nuclear lamina thickening. At the biochemical level,
      heterochromatin-associated proteins and LAP2 alpha were clustered at the nuclear
      interior following FTI-277 treatment, while they were unevenly distributed or
      absent in AFCMe-treated nuclei. The reported effects show that chromatin is an
      immediate target of FTI-277 and AFCMe and that dramatic remodeling of chromatin
      domains occurs following treatment with the drugs. These effects appear to
      depend, at least in part, on the accumulation of prelamin A forms, since
      impairment of prelamin A accumulation, here obtained by 5-azadeoxycytidine
      treatment, abolishes the chromatin effects. These results may be used to evaluate
      downstream effects of FTIs or other prelamin A inhibitors potentially useful for
      the therapy of laminopathies.

PMID- 18093585
TI  - Expression of brain-derived neurotrophic factor in cholinergic and dopaminergic
      amacrine cells in the rat retina and the effects of constant light rearing.
AB  - Brain-derived neurotrophic factor (BDNF) regulates many aspects of neuronal
      development, including survival, axonal and dendritic growth and synapse
      formation. Despite recent advances in our understanding of the functional
      significance of BDNF in retinal development, the retinal cell types expressing
      BDNF remains poorly defined. The goal of the present study was to determine the
      localization of BDNF in the mammalian retina, with special focus on the subtypes
      of amacrine cells, and to characterize, at the cellular level, the effects of
      constant light exposure during early postnatal period on retinal expression of
      BDNF. Retinas from 3-week-old rats reared in a normal light cycle or constant
      light were subjected to double immunofluorescence staining using antibodies to
      BDNF and retinal cell markers. BDNF immunoreactivity was localized to ganglion
      cells, cholinergic amacrine cells and dopaminergic amacrine cells, but not to AII
      amacrine cells regardless of rearing conditions. Approximately 75% of BDNF
      positive cells in the inner nuclear layer were cholinergic amacrine cells in
      animals reared in a normal lighting condition. While BDNF immunoreactivity in
      ganglion cells and cholinergic amacrine cells was significantly increased by
      constant light rearing, which in dopaminergic amacrine cells was apparently
      unaltered. The overall structure of the retina and the density of ganglion cells,
      cholinergic amacrine cells and AII amacrine cells were unaffected by rearing
      conditions, whereas the density of dopaminergic amacrine cells was significantly
      increased by constant light rearing. The present results indicate that
      cholinergic amacrine cells are the primary source of BDNF in the inner nuclear
      layer of the rat retina and provide the first evidence that cholinergic amacrine
      cells may be involved in the visual activity-dependent regulation of retinal
      development through the production of BDNF. The present data also suggest that
      the production or survival of dopaminergic amacrine cells is regulated by early
      visual experience.

PMID- 18093586
TI  - Leishmania infantum: prime boost vaccination with C-terminal extension of
      cysteine proteinase type I displays both type 1 and 2 immune signatures in BALB/c
      mice.
AB  - The aims of current study are to describe the immunogenicity and protective
      efficacy of prime boost vaccine using C-terminal extension (CTE) of cysteine
      proteinase type I of Leishmania infantum in BALB/c mice. Group I as vaccinated
      group primed with 100 microg of pcDNA-CTE and 3 weeks later boosted with
      combination of 30 microg rCTE, 50 microg of CpG and Montanide 720. Groups II and
      III were served as control groups. Although, this vaccination regimen did not
      protect mice against the infectious challenge but it was highly immunogenic.
      IgG2a has been raised strongly against rCTE in contrast to IgG1 and remains high
      at every time point under study. By analysis of CTE synthetic peptides (CTE100)
      before challenge, both IgG1 and IgG2a were produced and for all overlapping
      synthetic peptides (CTE 1-8) IgG1 raised significantly. This statue is changed at
      7 weeks after challenge and only CTE2 and CTE3 have shown to induce considerable
      amount of IgG1. In all groups, the level of IL-5 started to increase with high
      concentration shortly passing only 3 weeks after infectious challenge. In compare
      with two control groups, the vaccinated group produced significantly higher level
      of IL-5 at 7 weeks post-infection. The parasite burden of all groups is similar
      at 4 weeks post-challenge in both liver and spleen. In contrast, at 8 weeks post
      challenge, the spleen of the vaccinated group showed significantly higher level
      of parasite load in compare with two control groups. This study demonstrated that
      immunization with CTE display both type 1 and 2 immune signatures in experimental
      murine model of L. infantum infection.

PMID- 18093587
TI  - Hypothyroidism impairs antioxidant defence system and testicular physiology
      during development and maturation.
AB  - In the present study, effects of transient hypothyroidism (from birth to 30 days)
      and persistent hypothyroidism (from birth to 90 days) on testicular antioxidant
      defence system of mature rats were compared in order to know the role of
      hypothyroidism induced oxidative stress in testicular development and maturation.
      Rats were made hypothyroid by feeding lactating mothers and adult rats with 0.05%
      6-n-propyl thiouracil (PTU) in drinking water. PTU treatment for 30 days or for
      90 days to rats from birth resulted in a decrease in body weight at the age of 90
      days in comparison to the controls. The testicular germ cell counts were
      significantly decreased in persistent hypothyroid rats whereas they were
      increased in the transient hypothyroid rats. However, a significant reduction in
      the number of live sperms in epididymis of both 30 day and 90-day PTU treated
      rats was noticed on 90 days of age. Mitochondrial lipid peroxidation (LPx) levels
      were decreased in transient hypothyroidism whereas LPx and protein carbonylation
      were elevated during persistent hypothyroidism in the testis. Reduced testicular
      superoxide dismutase (SOD), catalase and glutathione reductase (GR) and
      glutathione peroxidase (GPx) activities were marked during transient
      hypothyroidism. In contrast, an elevation in SOD (PMF) and catalase activities
      with a significant decline in GPx and GR activities was found following
      persistent hypothyroidism. Marked histological changes were observed in the
      testis of both experimental groups. These results suggest a direct regulatory
      role of thyroid hormone on testicular physiology and antioxidant defence system
      during development and maturation.

PMID- 18093588
TI  - Studies of a receptor guanylyl cyclase cloned from Y-organs of the blue crab
      (Callinectes sapidus), and its possible functional link to ecdysteroidogenesis.
AB  - Crustacean Y-organs synthesize ecdysteroid molting hormones. Synthesis of
      ecdysteroids by Y-organs is negatively regulated by a polypeptide neurohormone,
      molt-inhibiting hormone (MIH). Our laboratory has recently cloned from Y-organs
      of the blue crab (Callinectes sapidus) a cDNA (CsGC-YO1) encoding a putative
      receptor guanylyl cyclase (CsGC-YO1). We hypothesize that CsGC-YO1 is an MIH
      receptor. In studies reported here, antipeptide antibodies (anti-CsGC-YO1) were
      raised against a fragment of the extracellular domain of CsGC-YO1. Western blots
      showed affinity purified anti-CsGC-YO1 bound to the heterologously expressed
      extracellular domain, and to a protein in Y-organs that corresponded in size to
      the theoretical molecular mass of CsGC-YO1. Immunocytochemical studies with anti
      CsGC-YO1 as primary antibody, showed CsGC-YO1 immunoreactivity was restricted to
      the peripheral margins of cells, and was not present in cytoplasm or nuclei. The
      results strongly suggest that CsGC-YO1 is a membrane-associated protein.
      Preincubation of Y-organs with anti-CsCG-YO1 blunted MIH-induced suppression of
      ecdysteroidogenesis. This finding represents the first demonstration of a link
      between CsGC-YO1 and MIH action. A real-time PCR assay for quantifying CsCG-YO1
      was developed and validated. The assay was used to determine the abundance of the
      CsCG-YO1 transcript in Y-organs during a molt cycle: the level of CsGC-YO1 in Y
      organs was elevated during intermolt (C(4)) and lower during premolt stages D(1)
      D(3). The data suggest that the biological action of CsGC-YO1 in Y-organs is
      likely to be most pronounced during intermolt. The combined results are
      consistent with the hypothesis that CsGC-YO1 is an MIH receptor.

PMID- 18093589
TI  - Genetic based sensorless hybrid intelligent controller for strip loop formation
      control between inter-stands in hot steel rolling mills.
AB  - Safe operating environment is essential for all complex industrial processes. The
      safety issues in steel rolling mill when the hot strip passes through consecutive
      mill stands have been considered in this paper. Formation of sag in strip is a
      common problem in the rolling process. The excessive sag can lead to scrap runs
      and damage to machinery. Conventional controllers for mill actuation system are
      based on a rolling model. The factors like rise in temperature, aging, wear and
      tear are not taken into account while designing a conventional controller.
      Therefore, the conventional controller cannot yield a requisite controlled
      output. In this paper, a new Genetic-neuro-fuzzy hybrid controller without
      tension sensor has been proposed to optimize the quantum of excessive sag and
      reduce it. The performance of the proposed controller has been compared with the
      performance of fuzzy logic controller, Neuro-fuzzy controller and conventional
      controller with the help of data collected from the plant. The simulation results
      depict that the proposed controller has superior performance than the other
      controllers.

PMID- 18093590
TI  - Pattern of orthopaedic injuries in bear attacks: report from a tertiary care
      centre in Kashmir.
AB  - Interaction between humans and wild animals has increased in recent times,
      because of overlap of habitats. A proportion of this interaction is violent. Most
      of the literature describing the injuries sustained by humans in such contact
      pertains to the involvement of soft tissues. Trauma to bones and joints is only
      witnessed when larger animals attack humans. We studied the pattern of
      orthopaedic injuries over a period of 2 years in a series of 32 cases presenting
      to our hospital with a history of being attacked by the Asian black bear (Ursus
      thibetanus). This paper also documents the complications and challenges involved
      in managing these injuries. We suggest that orthopaedic traumatologists need to
      be prepared to deal with such cases in areas where interaction between humans and
      large wild animals is manifest.

PMID- 18093591
TI  - Bryant traction in paediatric femoral shaft fractures, home traction versus
      hospitalisation.
AB  - AIM: To evaluate Bryant traction at home in terms of feasibility, morbidity,
      effect on length of hospital stay, outcome and costs. PATIENTS AND METHODS:
      Retrospective analysis of 54 children treated for femoral shaft fracture (1991
      2004). Results of 'home traction' (A, n=38) and 'hospital traction' (B, n=16)
      were compared. Data were collected regarding demographics, length of hospital
      stay, traction period, various aspects of the fractures, co-morbidity, morbidity,
      and follow-up. The parents' experience was evaluated by telephone questionnaire.
      RESULTS: Two early treatment failures occurred. One patient stopped home traction
      at 8 days due to skin problems and had a spica cast applied at another hospital,
      with subsequent development of a compartment syndrome. The other patient was
      placed in a hip spica after 2 weeks of hospital traction because of difficulty in
      getting satisfactory X-rays. At follow-up, one unacceptable shortening of 3 cm
      had occurred in the home traction group. There was only a significant difference
      in hospital stay (A 7.0 days versus B 22.5 days), total traction period (A 28.0
      days versus B 22.5 days) and costs (group B 3x versus group A). The parents were
      overall pleased with traction at home. Complications occurred as much in the home
      traction group as in the control group and fracture position at union was equal
      in both groups. CONCLUSIONS: Treatment with home traction is feasible, simple and
      effective; it reduces hospital stay to 1 week, and costs to one-third. Good
      patient selection and instructions of the parents are mandatory.

PMID- 18093592
TI  - Effects of sainfoin (Onobrychis viciifolia) extract and monomers of condensed
      tannins on the association of abomasal nematode larvae with fundic explants.
AB  - Tannin-rich forages offer an alternative to anthelmintic chemicals to control
      gastrointestinal nematodes. However, the mode of action of such bioactive plants
      still needs to be assessed. Previous studies have shown that extracts of tannin
      rich plants interfere with the first phase of host invasion, i.e., the
      exsheathment of infective larvae (L3s). In the current study, we examined the
      hypothesis that exposure to tannins could also affect the second phase of larval
      establishment, i.e., the tissue association/penetration of the exsheathed L3s
      into the digestive mucosae. An in vitro direct challenge technique using fundic
      explants was applied in this study. The main parasite model was Haemonchus
      contortus. The objectives were to verify: (i) whether a modification of the
      association/penetration of L3s with the mucosae occurred after contact with
      sainfoin extract; (ii) whether this is a dose-dependent phenomenon; (iii) whether
      tannins were responsible for these effects; (iv) whether these effects were
      dependent on the parasite species; and (v) how the biochemical structure of
      tannins might influence these effects. Following 3h contact with sainfoin extract
      at 1,200 microg/ml, the penetration of exsheathed L3s of H. contortus and
      Teladorsagia circumcincta into fundic explants was significantly reduced.
      Moreover, a dose-response relationship was found for H. contortus. For both
      nematodes, the changes were totally alleviated after addition of polyvinyl
      polypyrrolidone, an inhibitor of tannins, to the sainfoin extract, suggesting
      that tannins play a major role in the observed effects. Comparison of results
      obtained with different monomers of condensed tannins confirms a relationship
      between structure and activity, the prodelphinidin monomers and galloyl
      derivatives being more effective than the procyanidin monomers. Combined with the
      delay or the inhibition of larval exsheathment previously shown, these effects
      could explain how tanniniferous plants reduce the establishment of infective
      larvae in small ruminants.

PMID- 18093593
TI  - Anti-atherosclerotic properties of telmisartan in advanced atherosclerotic
      lesions in apolipoprotein E deficient mice.
AB  - Clinical studies have demonstrated that the inhibition of the renin-angiotensin
      system (RAS) by either an angiotensin-converting enzyme (ACE)-inhibitor or an
      angiotensin II receptor type 1 (AT(1))-antagonist reduces cardiovascular disease.
      The objective of this study was to evaluate underlying mechanisms of the AT(1)
      antagonist telmisartan in comparison to the ACE-inhibitor ramipril on advanced
      atherosclerotic lesions. Thirty-two-week-old apolipoprotein E deficient mice
      (n=60) exhibiting advanced atherosclerotic lesions were fed a chow diet
      supplemented with ramipril or telmisartan for 16 weeks. Twenty mice received a
      standard diet. Mice receiving telmisartan had a 38% and mice receiving ramipril
      had a 18% reduction in progression of atherosclerotic lesion size within the
      innominate artery. Signs of plaque instability such as frequency of intra-plaque
      hemorrhage and size of the necrotic cores were reduced in mice receiving
      telmisartan. Furthermore, telmisartan-treated mice had fewer macrophages and
      reduced expression of early growth response gene-1 (Egr-1) within the lesions.
      Electrophoretic mobility shift assays revealed reduced DNA-binding activity of
      nuclear factor kappaB (NFkappaB) in the aorta of telmisartan-treated mice. In
      vitro studies in mouse macrophages demonstrated enhanced promoter activation of
      the nuclear transcription factor peroxisome proliferators-activated receptor
      gamma (PPARgamma). Target genes of PPARgamma, such as inducible nitric oxide
      synthase, NFkappaB and Egr-1, showed reduced activity after telmisartan
      pretreatment. These data suggest that chronic inhibition of the RAS by
      telmisartan prevails in reducing advanced atherosclerosis and promoting plaque
      stability over ramipril, possibly through the reduced activity of the pro
      inflammatory transcription factors NFkappaB and Egr-1 and through the activation
      of PPARgamma.

PMID- 18093594
TI  - The clinical reality of guidelines for primary prevention of cardiovascular
      disease in type 2 diabetes in Italy.
AB  - INTRODUCTION AND AIM: Guidelines for cardiovascular prevention in diabetes have
      been issued by the national and international scientific societies. No audit as
      ever been performed to evaluate the implementation of these documents in clinical
      practice in Italy. The study evaluates the prevalence, treatment, and control of
      major cardiovascular risk factors in type 2 diabetic patients, to assess the
      clinical practice of primary cardiovascular prevention in type 2 diabetes.
      PATIENTS AND METHODS: Two thousand four hundred and sixty-five men and women with
      type 2 diabetes, aged 50-75 and free of cardiovascular events were recruited on a
      consecutive basis at 10 hospital based outpatients diabetes clinics. Clinical
      variables were measured by standard protocol. Biochemical parameters were
      evaluated at each centre. The laboratories were monitored by an external quality
      control assessment in order to reach and maintain a standard of quality and
      traceability among the participating centres. RESULTS: A minority of patients
      (5%) met the recommended targets for LDL cholesterol, blood pressure, glycated
      haemoglobin and smoking habits, whereas the vast majority (66%) had
      unsatisfactory control of three or more of the above. Achievement of desirable
      control of risk factors differed according to gender and known diabetes duration.
      Lipid lowering and, to a lesser extent, antihypertensive medications were under
      used and their titration insufficiently target-driven. Prophylactic use of
      antiplatelet agents was scarce, only one out of five patients was treated
      independent of absolute cardiovascular risk. CONCLUSION: In clinical practice
      there is poor adherence to national and international guidelines for primary
      cardiovascular prevention in type 2 diabetes in Italy. The study underlines the
      great potential for prevention, particularly in women and in high-risk patients.

PMID- 18093595
TI  - Phosphorus levels are associated with subclinical atherosclerosis in the general
      population.
AB  - BACKGROUND: Elevated serum phosphorus has been linked to mortality among patients
      with renal failure and in one study in the general population. The aim of our
      study was to examine the association of serum phosphorus level with carotid
      atherosclerosis in the general population. METHODS: We determined the association
      of serum phosphorus levels with carotid intima-media thickness (cIMT) in 13,340
      subjects 45-64 years old without known coronary heart disease, stroke, or renal
      disease from the Atherosclerosis Risk in Communities (ARIC) study. RESULTS:
      Phosphorus levels were significantly associated with age, female gender, diabetes
      mellitus, hypertension, hypercholesterolemia and fibrinogen levels (p < 0.0001
      for each), but not with estimated glomerular filtration rate (eGFR). Age- and sex
      adjusted mean cIMT ranged from 0.718 to 0.736 mm for the lowest to the highest
      quintile of serum phosphorus (p-value for trend < 0.0001). This relationship was
      attenuated but remained statistically significant after adjustment for
      atherosclerotic risk factors and eGFR (trend p < 0.0001) in men but not in women.
      In a multivariable model, a one standard deviation increase in baseline serum
      phosphorus (0.48 mg/dL) was associated with a 0.012 mm increase in mean cIMT (p <
      0.007) in men. CONCLUSION: In a population-based cohort of subjects free of overt
      cardiovascular and renal disease serum phosphorus was positively associated with
      cIMT independent of traditional risk factors for atherosclerosis and eGFR in men
      but not in women.

PMID- 18093596
TI  - Reduced plaque formation induced by rosiglitazone in an STZ-diabetes mouse model
      of atherosclerosis is associated with downregulation of adhesion molecules.
AB  - Adhesion molecules have been implicated in the development and progression of
      cardiovascular disease, which is highly prevalent in people with diabetes.
      Adhesion molecules can mediate adhesion of leukocytes to the endothelium.
      Furthermore, P-selectin expressed on platelets is able to mediate the adhesion of
      leukocytes to platelets. In this study, we examine the in-vivo and in-vitro
      effects of rosiglitazone with particular emphasis on three important adhesion
      molecules (VCAM-1, ICAM-1 and P-selectin). In the aorta of STZ-diabetic
      apolipoprotein E-deficient (apoE KO) mice, rosiglitazone significantly reduced
      both total and arch plaque area. The mechanism for this appeared to be reduced
      macrophage infiltration into the atherosclerotic plaque which was also associated
      with reduced mRNA levels for VCAM-1, ICAM-1, MCP-1 and P-selectin in the aorta.
      In-vitro studies revealed reduced cell adhesion of monocytic cells (THP-1) to
      fibrinogen and endothelial cells (HUVEC) after incubation with rosiglitazone.
      Furthermore, the reduction in leukocyte adhesion also correlated with significant
      reductions in mRNA levels for VCAM-1, ICAM-1 and P-selectin indicating that
      reduced macrophage infiltration in atherosclerotic plaques may occur as a result
      of a direct effect of rosiglitazone on adhesion molecules in both monocytes and
      endothelial cells. Thus, we have shown that rosiglitazone appears to have direct
      anti-atherosclerotic effects in an animal model of diabetes-associated
      atherosclerosis which are at least partly due to effects on VCAM-1, ICAM-1, MCP-1
      and P-selectin expression which leads to decreased leukocyte adhesion and
      macrophage infiltration.

PMID- 18093597
TI  - Effect of rosuvastatin on insulin sensitivity in an animal model of insulin
      resistance: evidence for statin-induced hepatic insulin sensitization.
AB  - Statin-treatment of fructose-fed/insulin resistant hamsters was recently shown to
      ameliorate metabolic dyslipidemia and hepatic VLDL overproduction. Here, we
      provide evidence that rosuvastatin treatment of insulin resistant hamsters can
      induce improvements in hepatic and whole body insulin sensitivity. Treatment with
      10 mg/kg/day rosuvastatin for 10 days significantly reduced fasting insulin (
      59%) and triglyceride (-50%) levels in fructose-fed hamsters (p<0.05). Following
      an intraperitoneal (IP) glucose challenge, rosuvastatin-treated hamsters
      exhibited enhanced glucose clearance compared to untreated hamsters maintained on
      the high-fructose diet (area under curve (AUC)=1772+/-223 mM min vs. 2413+/-253
      mM min, respectively; p<0.002) with a significant reduction in 2h post-challenge
      glucose (n=5, p<0.02). Rosuvastatin-treatment also significantly improved
      sensitivity to an IP insulin challenge (AUC=314+/-39 mM min vs. 195+/-22 mM min
      for rosuvastatin-treated and fructose-fed hamsters, respectively; p<0.04, n=3).
      At the molecular level, significant increases in tyrosine-phosphorylation of the
      hepatic insulin receptor and IRS-1 were observed for rosuvastatin-treated
      hamsters (+37% and +58%, respectively) compared to fructose-fed controls
      following an intravenous (IV) bolus of insulin (p<0.05). Increases in insulin
      receptor and IRS-1 phosphorylation were also observed in muscle and adipose
      tissue. Analysis of hepatic Akt phosphorylation and mass revealed a small (25%)
      increase in serine phosphorylation of Akt with no significant change in Akt mass,
      although serine-phosphorylation and mass of Akt2 were significantly increased
      (+32%, p=0.03, and +42%, p=0.01, respectively). Interestingly, expression of PTP
      1B, a key negative regulator of insulin signaling, showed a non-significant trend
      toward reduction in liver and was significantly reduced in adipose tissue (-20%
      and -37%, respectively). Taken together, these data suggest that statin-treatment
      increases whole body and peripheral tissue insulin sensitivity via improved
      cellular insulin signal transduction.

PMID- 18093598
TI  - Using the method of homogenization to calculate the effective diffusivity of the
      stratum corneum with permeable corneocytes.
AB  - The stratum corneum is the outermost layer of the skin, which acts as a barrier
      membrane against the penetration of molecules into and out of the body. It has a
      biphasic structure consisting of keratinized cells (corneocytes) that are
      embedded in a lipid matrix. The macroscopic transport properties of the stratum
      corneum are functions of its microstructure and the transport properties of the
      corneocytes and the lipid matrix, and are of considerable interest in the context
      of transdermal drug delivery and quantifying exposure to toxins, as well as for
      determining the relation of skin disorders to disruption of the stratum corneum
      barrier. Due to the complexity of the tissue and the difference in length scales
      involved in its microstructure, a direct analysis of the mass transport
      properties of the stratum corneum is not feasible. In this study, we undertake an
      approach where the macroscopic diffusion tensor of the stratum corneum is
      obtained through homogenization using the method of asymptotic expansions. The
      biphasic structure of the stratum corneum is fully accounted for by allowing the
      corneocytes to be permeable and considering the partitioning between the
      corneocytes and the lipid phases. By systematically exploring the effect of
      permeable corneocytes on the macroscopic transport properties of the stratum
      corneum, we show that solute properties such as lipophilicity and relative
      permeabilities in the two phases have large effects on its transdermal diffusion
      behavior.

PMID- 18093599
TI  - A comparison of passive flexion-extension to normal gait in the ovine stifle
      joint.
AB  - Obtaining accurate values of joint tissue loads in human subjects and animals in
      vivo requires exact 3D-reproduction of joint kinematics and comparisons of in
      vivo motions between subjects and animals, and also necessitates an accurate
      reference position. For the knee, passive flexion-extension of isolated joints by
      hand has been assumed to produce bony motions similar to those of normal gait. We
      hypothesized that passive flexion-extension kinematics would not accurately
      reproduce in vivo gait, and, further, that such kinematics would vary
      significantly between testers. In vivo gait motions of four ovine stifle joints
      were measured in six degrees of freedom, as were passive flexion-extension
      motions after sacrifice. Passive flexion-extension motions were performed by
      three testers on the same stifle joints used in vitro. Results showed
      statistically significant differences in all degrees of freedom, with the largest
      differences in the proximal-distal and internal-external directions. Differences
      induced by muscle loads and kinetic factors in vivo were most evident during
      stance and hoof-off phases of gait. The in vitro passive paths generated by hand
      created motions with large variability both between and within individual
      testers. The user dependence and "area" of motion of passive flexion-extension
      indicates that passive flexion-extension is contained in a volume of motion,
      rather than constrained to a unique path. The assumption that the passive path
      has relevance to precise bone positions during normal in vivo gait is not
      supported by these results. Thus, using passive flexion-extension as a reference
      between joints may introduce large motion variability in the observed outcome,
      and large potential errors in determining joint tissue loads.

PMID- 18093600
TI  - Acquisition of full-field strain distributions on ovine fracture callus cross
      sections with electronic speckle pattern interferometry.
AB  - This study evaluated the feasibility of assessing continuous strain distributions
      on fracture callus cross-sections with an electronic speckle pattern
      interferometry (ESPI) system. Mid-sagittal callus cross-sections were harvested
      from ovine tibiae. One low stiffness (LS) specimen and one high stiffness (HS)
      specimen were selected to evaluate the feasibility for strain acquisition over a
      range of callus properties. The HS specimen was 147 times stiffer in compression
      than the LS specimen. ESPI captured continuous strain distributions on both
      specimens. Peak strain was located adjacent to cortical boundaries in the
      osteotomy gap. In response to 5N compression, peak compressive strain of 5.8% in
      the LS specimen was over two orders of magnitude higher than peak compressive
      strain of 0.013% in the HS specimen. In conclusion, ESPI-based strain acquisition
      enables reproducible quantification of strain distributions on callus cross
      sections. Such measurements may support validation of computational models and
      evaluation of experimental results in fracture healing research.

PMID- 18093601
TI  - Determination of aflatoxins in hazelnuts by various sample preparation methods
      and liquid chromatography-tandem mass spectrometry.
AB  - A sensitive and reliable liquid chromatography-tandem mass spectrometric with
      electrospray ionization method for determining aflatoxins in hazelnuts has been
      developed. Three different extraction techniques, such as homogenization,
      ultrasonic extraction, and matrix solid phase dispersion have been tested and
      compared in terms of recovery, matrix effect, accuracy and precision. Ultrasound
      extraction was the most performing sample preparation method. Absolute recoveries
      for analytes and I.S. ranged from 93 to 101%. Accuracy and precision were
      calculated using matrix matched calibration, and ranged 91-102% and 2-11%,
      respectively. CC alpha and CC beta for aflatoxin B1 (EU limit=2 microg/kg) were
      2.15 and 2.33 microg/kg, respectively. A ruggedness test performed on three other
      matrices demonstrated that sonication time was critical and a matrix matched
      calibration must be constructed for every sort of matrix.

PMID- 18093602
TI  - Method to determine enantiomeric excess of glucose by nonchiral high-performance
      liquid chromatography using circular dichroism detection.
AB  - Using nonchiral high-performance liquid chromatography (HPLC) coupled with a
      circular dichroism (CD) detector, we developed a new method to determine the
      enantiomeric excess (e.e.) of glucose derivatized with chromophores (p
      bromobenzoate). This method is suitable for microscale analysis of glycoside and
      saccharide. As an application of this method, the enantiomeric excess of the
      component glucose of a glucan was assayed.

PMID- 18093603
TI  - Solving matrix-effects exploiting the second order advantage in the resolution
      and determination of eight tetracycline antibiotics in effluent wastewater by
      modelling liquid chromatography data with multivariate curve resolution
      alternating least squares and unfolded-partial least squares followed by residual
      bilinearization algorithms I. Effect of signal pre-treatment.
AB  - The effect of piecewise direct standardization (PDS) and baseline correction
      approaches was evaluated in the performance of multivariate curve resolution (MCR
      ALS) algorithm for the resolution of three-way data sets from liquid
      chromatography with diode-array detection (LC-DAD). First, eight tetracyclines
      (tetracycline, oxytetracycline, chlorotetracycline, demeclocycline, methacycline,
      doxycycline, meclocycline and minocycline) were isolated from 250 mL effluent
      wastewater samples by solid-phase extraction (SPE) with Oasis MAX 500 mg/6 mL
      cartridges and then separated on an Aquasil C18 150 mm x 4.6mm (5 microm particle
      size) column by LC and detected by DAD. Previous experiments, carried out with
      Milli-Q water samples, showed a considerable loss of the most polar analytes
      (minocycline, oxitetracycline and tetracycline) due to breakthrough. PDS was
      applied to overcome this important drawback. Conversion of chromatograms obtained
      from standards prepared in solvent was performed obtaining a high correlation
      with those corresponding to the real situation (r2 = 0.98). Although the
      enrichment and clean-up steps were carefully optimized, the sample matrix caused
      a large baseline drift, and also additive interferences were present at the
      retention times of the analytes. These problems were solved with the baseline
      correction method proposed by Eilers. MCR-ALS was applied to the corrected and
      uncorrected three-way data sets to obtain spectral and chromatographic profiles
      of each tetracycline, as well as those corresponding to the co-eluting
      interferences. The complexity of the calibration model built from uncorrected
      data sets was higher, as expected, and the quality of the spectral and
      chromatographic profiles was worse.

PMID- 18093604
TI  - Novel precursor-derived Si-C-N ceramic material for purification application.
AB  - Metagenomic DNA (gDNA) is an important research topic because uncultivated
      microorganisms represent an interesting reservoir of genes with potential
      biotechnological applications. Here we describe a novel Si-C-N chromatography
      approach of gDNA extraction from environmental samples. Amorphous Si-C-N ceramic
      was obtained by the pyrolysis of a polymer precursor (polycarbosilazane) at 1350
      degrees C in Ar. The purified gDNA fragments were at least 12 kilo base pairs in
      size and were sufficiently free of contaminants, thus were applicable to both
      restriction enzyme digestion using five different enzymes and polymerase chain
      reaction amplification for detecting phylogenetic groups of native microorganisms
      in environmental samples. This Si-C-N material produces pure gDNA that can be
      utilized in some of the most common molecular biological procedures applied in
      the purification step.

PMID- 18093605
TI  - High-performance liquid chromatography analysis of ten dyes for control of safety
      of commercial articles.
AB  - Two high-performance liquid chromatographic methods, with ultraviolet-visible
      spectrophotometry detection (HPLC-UV/Vis) and with tandem mass spectrometry
      triple quadrupole interfaced with positive ion mode electrospray ionization
      detection (HPLC-ESI+-QqQ-MS/MS), for determination and quantification of ten
      commercial dyes are proposed for control in commercial products. Multiple peaks
      observed for some of the studied dyes in HPLC-UV/Vis chromatograms forced to
      obtain structural information by HPLC-ESI-MS/MS method with scan mode. The
      quality parameters of the two proposed chromatographic methods were evaluated for
      different requirements of normative, showing detection (LODs) and quantification
      (LOQs) limits around 60-890 and 200-2990 microg L(-1) for HPLC-UV/Vis, and 4.54
      14.3 and 15.0-47.6 microg L(-1) for HPLC-ESI+-QqQ-MS/MS.

PMID- 18093606
TI  - Novel monolithic poly(p-methylstyrene-co-bis(p-vinylbenzyl)dimethylsilane)
      capillary columns for biopolymer separation.
AB  - Hydrophobic organo-silane based monolithic capillary columns were prepared by
      thermally initiated free radical polymerisation within the confines of 200 microm
      i.d. fused silica capillaries. A novel crosslinker, namely bis(p
      vinylbenzyl)dimethylsilane (BVBDMS), was copolymerised with p-methylstyrene (MS)
      in the presence of 2-propanol and toluene, using alpha,alpha'-azoisobutyronitrile
      (AIBN) as initiator. Monolithic capillary columns, differing in the total
      monomer, microporogen content and microporogen nature were fabricated and the
      chromatographic efficiency of each monolith, regarding the separation of
      proteins, peptides and oligonucleotides, was evaluated and compared. Changes in
      monolith morphology were monitored by scanning electron microscopy (SEM).
      Porosity and specific surface areas of the supports were studied by means of
      mercury intrusion porosimetry and BET measurements, respectively. Pressure drop
      vs. flow rate measurements proved the prepared poly(p-methylstyrene-co-bis(p
      vinylbenzyl)dimethylsilane) (MS/BVBDMS) monoliths to be mechanically stable and
      swelling propensity (SP) factors of 0.78-1.10 indicate high crosslinking
      homogeneity.

PMID- 18093607
TI  - Comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry
      peak sorting algorithm.
AB  - We report a novel peak sorting method for the two-dimensional gas
      chromatography/time-of-flight mass spectrometry (GC x GC/TOF-MS) system. The
      objective of peak sorting is to recognize peaks from the same metabolite
      occurring in different samples from thousands of peaks detected in the analytical
      procedure. The developed algorithm is based on the fact that the chromatographic
      peaks for a given analyte have similar retention times in all of the
      chromatograms. Raw instrument data are first processed by ChromaTOF (Leco)
      software to provide the peak tables. Our algorithm achieves peak sorting by
      utilizing the first- and second-dimension retention times in the peak tables and
      the mass spectra generated during the process of electron impact ionization. The
      algorithm searches the peak tables for the peaks generated by the same type of
      metabolite using several search criteria. Our software also includes options to
      eliminate non-target peaks from the sorting results, e.g., peaks of contaminants.
      The developed software package has been tested using a mixture of standard
      metabolites and another mixture of standard metabolites spiked into human serum.
      Manual validation demonstrates high accuracy of peak sorting with this algorithm.

PMID- 18093608
TI  - Characterisation by liquid chromatography coupled to electrospray ionisation ion
      trap mass spectrometry of phloroglucinol and 4-methylcatechol oxidation products
      to study the reactivity of epicatechin in an apple juice model system.
AB  - The reactivity of the (-)-epicatechin structure towards caffeoylquinic acid o
      quinones was studied in an apple juice model solution. The approach consisted in
      considering separately the reactivities of the two phenolic moieties of an (-)
      epicatechin molecule: phloroglucinol and 4-methylcatechol were chosen to
      represent A- and B-rings, respectively. The oxidation products were characterised
      by RP-HPLC coupled with electrospray ionisation Mass spectrometry (MS). The
      reactivities of the A- and B-rings were clearly different on the basis of the
      oxidation products formed. Both A- and B-rings could be involved in covalent bond
      formation, but electron transfers only occurred with the B-ring. Most of the (-)
      epicatechin oxidation products were linked by A/B-ring linkage ("head-to-tail"
      intermolecular coupling). After this first dimerisation step, intramolecular
      reactions seemed to be favoured. Therefore, the complexity of oxidation products
      in apple juice does not only result from an extensive polymerisation of native
      phenolic compounds, but also from a multiplicity of small molecules in different
      oxidation states and isomeric forms.

PMID- 18093609
TI  - On-line coupling of extraction with gas chromatography.
AB  - A recent trend in the development of analytical methodologies is the integration
      of the sample preparation step directly with the chromatographic system. In
      integrated on-line systems, extraction, clean-up, separation and detection are
      connected with each other and the whole analytical procedure takes place in a
      closed, usually automated system. In this review, a critical overview of the
      principles and benefits of on-line coupling of extraction with gas chromatography
      is presented. Techniques suitable for the extraction and analysis of various
      types of compounds in both solid and liquid samples are presented. The potential
      of on-line techniques is discussed and illustrated with selected examples.

PMID- 18093610
TI  - Using phospholipid Langmuir and Langmuir-Blodgett films as matrix for urease
      immobilization.
AB  - The immobilization of enzymes in organized two-dimensional matrices is a key
      requirement for many biotechnological applications. In this paper, we used the
      Langmuir-Blodgett (LB) technique to obtain controlled architectures of urease
      immobilized in solid supports, whose physicochemical properties were investigated
      in detail. Urease molecules were adsorbed at the air-water interface and
      incorporated into Langmuir monolayers of the phospholipid dipalmitoyl
      phosphatidyl glycerol (DPPG). Incorporation of urease made DPPG monolayers more
      flexible and caused the reduction of the equilibrium and dynamic elasticity of
      the film. Urease and DPPG-urease mixed monolayers could be transferred onto solid
      substrates, forming LB films. A close packing arrangement of urease was obtained,
      especially in the mixed LB films, which was inferred with nanogravimetry and
      electrochemistry measurements. From the blocking effect of the LB films deposited
      onto indium tin oxide (ITO) substrates, the electrochemical properties of the LB
      films pointed to a charge transport controlled by the lipid architecture.

PMID- 18093611
TI  - Effect of polycrystalline structure of TiO2 particles on the light scattering
      efficiency.
AB  - The opacifying power of synthesized polycrystalline TiO2 particles in a cellulose
      matrix was found experimentally and theoretically to be superior to that of a
      commercial rutile pigment, depending on crystal structure of the synthesized
      particles. The crystal structure of the particles was varied by calcination of
      amorphous titania nanoparticles at different temperatures and was characterized
      using SEM, TEM, and XRD. Polycrystalline anatase pigments had less opacifying
      power than commercial rutile, while polycrystalline pigments containing a one-to
      one mixture of anatase and rutile had similar opacifying power as the commercial
      pigment if they have a similar overall particle size. The polycrystalline rutile
      pigments composed of a linear linkage of several individual rutile crystals gave
      6% more opacity than the commercial rutile pigment. Theoretical light scattering
      calculations using the T-matrix method showed the light scattering efficiency of
      linearly arranged polycrystalline rutile particles to depend on number and size
      of crystals composing the particle. It is suggested that the efficiency of rutile
      pigments can be increased dramatically by controlling both the primary crystal
      size and the overall particle size. It is believed that the greater than expected
      light scattering efficiency of the biphasic pigment results from reflection and
      refraction of light at the grain boundaries between crystals of different phase,
      which have different refractive indices.

PMID- 18093612
TI  - A sensitive sandwich enzyme immunoassay for free or complexed Clostridium
      botulinum neurotoxin type A.
AB  - Fourteen monoclonal antibodies (mAbs) against Clostridium botulinum type A
      neurotoxin were raised in mice using a carboxy terminal fragment of the toxin for
      immunization. A two-site immunometric assay was developed which allowed detection
      of 8 LD(50)/ml (40 pg/ml) botulinum neurotoxin A and an accurate quantification
      close to 25 LD(50)/ml (150 pg/ml). No cross-reactivity was observed with other
      toxinotypes. During the development of this assay, interference induced by
      associated protein was observed. By comparing the effect of different buffers, a
      buffer composed with Tris-HCl and NaCl salts was demonstrated to dissociate
      protein complexed with the neurotoxin A. Applied to the measurement of the toxin
      in different matrices, this dissociating buffer ensures the correct
      quantification.

PMID- 18093613
TI  - Juvenile hormone analogs do not affect directly the activity of the ecdysteroid
      receptor complex in insect culture cell lines.
AB  - During insect development, ecdysteroids and juvenile hormones (JHs) interact to
      regulate larval growth, metamorphosis and reproduction but the molecular
      mechanisms by which both hormones influence each other's activity remain unknown.
      Because of their ease of use and straightforward genetic manipulation, insect
      cell lines often have been used to clarify the actions and interactions of
      hormones at the molecular level. Here we report on the use of two insect culture
      cell lines, Drosophila melanogaster S2 and Bombyx mori Bm5 cells, to investigate
      two molecular processes in which ecdysteroids and JH have been shown to interact:
      (1) direct modulation of the activity of the ecdysteroid receptor transcription
      complex and (2) interference at the level of induction of the primary gene E75.
      Our data do not support JH analogs (JHAs) acting through the above processes:
      'antagonism' of ecdysteroid receptor activity by JHAs correlated with
      cytotoxicity and induction of E75 expression by JHAs was not demonstrated.
      However, we confirm previous studies in which it was observed that methoprene can
      partially reverse the growth inhibition by 20E in S2 cells (but not Bm5 cells).
      Therefore, the molecular mechanism by which both hormones influence each other's
      activity to regulate cell growth in S2 cells remains unknown.

PMID- 18093614
TI  - Identification of Vibrio spp. in vibriosis Penaeus vannamei using developed
      monoclonal antibodies.
AB  - Immunohistochemical study using monoclonal antibodies specific to various shrimp
      viruses and Vibrio spp. was performed in shrimp samples died from unknown cause
      with symptoms of black stripes on lateral sides of cephalothorax or smoky body
      coloration. The positive results in muscular tissue were obtained with MAb VAL57
      (specific to Vibrio spp.) and in hepatopancreas tissues with MAbs VVB158
      (specific to V. vulnificus) and VPC701 (specific to V. parahaemolyticus). Twelve
      isolates of Vibrio spp. isolated from shrimp tissues were identified with various
      MAbs by dot blotting, biochemical tests and 16S rRNA gene. The results revealed
      three groups of V. vulnificus and one group of V. shilonii. All four groups of
      isolated Vibrio spp. were immunologically and biochemically different. None of
      the V. parahaemolyticus-like bacterium was isolated. The results demonstrated
      that the mortality in shrimp is accompanied by the presence of Vibrio spp.

PMID- 18093615
TI  - Pain perception in schizophrenia: no changes in diffuse noxious inhibitory
      controls (DNIC) but a lack of pain sensitization.
AB  - BACKGROUND: Pain is a dynamic phenomenon resulting from the activity of both
      excitatory (e.g. sensitization) and inhibitory endogenous modulation systems.
      Preliminary experimental studies have shown diminished pain sensitivity in
      schizophrenia patients. The objective of the study was to investigate the role of
      excitatory and inhibitory systems on pain perception in schizophrenia. METHODS:
      Participants were 23 patients with a schizophrenia-spectrum disorder (DSM-IV
      criteria) and 29 healthy volunteers, who did not differ in age, sex or ethnicity.
      Excitatory and inhibitory systems were elicited using a temporal summation test
      (Peltier thermode) administered before and after activation of the diffuse
      noxious inhibitory control (DNIC) by means of a cold-pressor test. RESULTS: Time
      was a significant predictor of pain scores in controls, but not in patients. That
      is, pain ratings increased during the tonic thermal stimulation among controls
      but not in schizophrenia patients. When correlation coefficients (between time
      and pain ratings) for patients and controls were compared, the correlation
      coefficient emerged as significantly weaker in the schizophrenia group (Z=12.04;
      p=0.0001), suggesting a lack of sensitization in schizophrenia. DNIC was similar
      in magnitude in both patients and controls. CONCLUSIONS: Diminished pain
      sensitivity in schizophrenia may be related to abnormal excitatory mechanisms,
      but not to DNIC. More studies are needed to better characterize the
      neurophysiological and neurochemical mechanisms involved in the lack of
      sensitization in schizophrenia.

PMID- 18093616
TI  - The evolution of hermaphroditism.

PMID- 18093617
TI  - Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung
      fibroblasts.
AB  - Pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone) is a novel anti-fibrotic and anti
      inflammatory agent that inhibits the progression of fibrosis in animal models and
      patients with idiopathic pulmonary fibrosis (IPF). Heat shock protein (HSP) 47, a
      collagen-specific molecular chaperone, is involved in the processing and/or
      secretion of procollagen and plays an important role in the pathogenesis of IPF.
      The present study evaluated the in vitro effects of pirfenidone on expression of
      HSP47 and collagen type I in cultured normal human lung fibroblasts (NHLF).
      Expression levels of HSP47 and collagen type I in NHLF stimulated by transforming
      growth factor (TGF)-beta1 were evaluated genetically, immunologically and
      immunocytochemically. Treatment with TGF-beta1 stimulated both mRNA and protein
      expressions of both HSP47 and collagen type I in NHLF, and pirfenidone
      significantly inhibited this TGF-beta1-enhanced expression in a dose-dependent
      manner. We concluded that the anti-fibrotic effect of pirfenidone may be mediated
      not only through direct inhibition of collagen type I expression but also at
      least partly through inhibition of HSP47 expression in lung fibroblasts, with a
      resultant reduction of collagen synthesis in lung fibrosis.

PMID- 18093618
TI  - Curcumin treatment enhances islet recovery by induction of heat shock response
      proteins, Hsp70 and heme oxygenase-1, during cryopreservation.
AB  - Limited recovery of islets post-cryopreservation influences graft survival and
      transplantation efficiency during diabetes treatment. As curcumin, a potent
      antioxidant/radical scavenging compound, protects islets against beta cell
      toxins, we hypothesized that inclusion of curcumin during cryopreservation or
      during post-thaw culture or both may rescue islets from cryoinjury. To test the
      effect of curcumin inclusion on islet recovery murine islets were isolated by the
      collagenase digestion, cultured for 48 h, cryopreserved using dimethylsulphoxide
      as cryoprotectant -- with or without curcumin (10 microM) -- and then slow cooled
      to -40 degrees C before immersing them in liquid nitrogen for 7 days. Following
      rapid thawing with sucrose gradient and 24 h post-thaw culture -- in presence or
      absence of curcumin (10 microM) -- islet viability and functionality were
      determined. Islet recovery in curcumin treated groups was significantly higher
      than in groups where islets were cryopreserved without curcumin. Islets
      cryopreserved with curcumin also showed more intact islets as well as better
      morphology as compared to islets cryopreserved without curcumin. Curcumin treated
      islets also showed significant inhibition of ROS generation as compared to islets
      cryopreserved without curcumin. Glucose responsiveness and insulin secretion in
      islets cryopreserved with curcumin was equal to that of the freshly isolated
      islets as against islets cryopreserved without curcumin. Elevated level of Hsp 70
      and HO-1 were observed in islets cryopreserved with curcumin and may contribute
      to curcumin-induced islet rescue. Hence, we conclude that inclusion of curcumin
      into cryopreservation medium inhibits ROS generation and corresponding islet
      damage and dysfunction.

PMID- 18093619
TI  - Sediment features, macrozoobenthic assemblages and trophic relationships
      (delta13C and delta15N analysis) following a dystrophic event with anoxia and
      sulphide development in the Santa Giusta lagoon (western Sardinia, Italy).
AB  - Macrozoobenthic assemblages and stable carbon (delta(13)C) and nitrogen
      (delta(15)N) isotope values of various primary producers (macroalgae and
      angiosperms) and consumers (macroinvertebrate filter/suspension feeders, deposit
      feeders, detritivores/omnivores and carnivores and fishes) were studied in the
      Santa Giusta lagoon (Sardinia, Italy) before (spring) and after (autumn) a
      dystrophic event which occurred in the summer of 2004. A few days after the
      dystrophy, the physico-chemical characteristics of sediments and macrozoobenthic
      assemblages were also investigated. In the latter occasion, high total organic
      carbon (3.9%) and organic matter (15.9%) contents of surface sediments went
      together with peaks in acid-volatile sulphide concentrations. Certain immediate
      effects were quite extreme, such as the drastic reduction in macrozoobenthos and
      the massive fish kill in August 2004. Among the macrozoobenthos, there were few
      individuals of chironomid larvae and Capitella cf. capitata left. However, by
      October, chironomid larvae were numerous, indicating a lack of predators (e.g.
      fish) and competitors. In addition, some bivalve species and polychaetes which
      were absent, or present in small numbers before the event, became relatively
      numerous. The results are discussed based on a knowledge of the sulphide
      tolerance of these species. Stable isotope analysis clearly showed that the basal
      level of the food web for most consumers consisted mainly of macroalgae and
      sedimentary organic matter, and that the values before and after the dystrophic
      event were not significantly different from one another. This indicates that the
      relations among different trophic levels were quickly restored following the
      dystrophic event.

PMID- 18093620
TI  - A tribute to John Stuart Gray (1941-2007).

PMID- 18093621
TI  - AM404, an anandamide transport inhibitor, reduces plasma extravasation in a model
      of neuropathic pain in rat: role for cannabinoid receptors.
AB  - Neuropathic pain consequent to peripheral nerve injury has been associated with
      local inflammation. Following noxious stimulation afferent fibres release
      substance P (SP) and calcitonin-gene related peptide (CGRP), which are closely
      related to oedema formation and plasma leakage. The effect of the anandamide
      transport blocker AM404 has been studied on plasma extravasation after chronic
      constriction injury (CCI) which consists in a unilateral loose ligation of the
      rat sciatic nerve (Bennett and Xie, 1988). AM404 (1-3-10 mg kg(-1)) reduced
      plasma extravasation in the legated paw, measured as mug of Evans Blue per gram
      of fresh tissue. A strong effect on vascular permeability was also produced by
      the synthetic cannabinoid agonist WIN 55,212-2 (0.1-0.3-1 mg kg(-1)). Using
      specific antagonists or enzyme inhibitors, we demonstrate that cannabinoids act
      at several levels: data on the 3rd day suggest a strong involvement of substance
      P (SP) and calcitonin gene-related peptide (CGRP) in the control of vascular
      tone, whereas at the 7th and 14th days the major role seems to be played by
      prostaglandins (PGs) and nitric oxide (NO). Capsaicin injection in ligated paws
      of AM404- or WIN 55,212-2-treated rats resulted in an increase of Evans Blue
      extravasation, suggesting the involvement of the cannabinergic system in the
      protective effect of C fibres of ligated paws. Taken together, these data
      demonstrate the efficacy of cannabinoids in controlling pain behaviour through
      the modulation of several pain mediators and markers of vascular reactivity, such
      as SP, CGRP, PGs and NO.

PMID- 18093622
TI  - The anatomo-functional connectivity of language revisited. New insights provided
      by electrostimulation and tractography.
AB  - In addition to the seminal lesion studies of aphasiology, the development of
      functional neuroimaging has allowed a better understanding of the neural
      foundations of language. However, despite a substantial improvement in the
      knowledge of the cortical networks organization, the underlying subcortical
      association circuits have received less attention. Recent advances in fiber
      tracking using diffusion tensor imaging, combined with personal studies using
      intraoperative electrostimulation, which temporarily inactivates restricted
      regions during brain surgery, have enabled to map language pathways in humans
      with spatiotemporal resolution unmatched by other techniques. On the basis of
      these new insights, my purpose is to revisit the anatomo-functional connectivity
      of language. First, I discuss the role of the white bundles thought to be
      essential for language, with special emphasis regarding the structure-function
      relationships pertaining to the distinct subcomponents of language. Second, I
      propose an integrative view of connectivity, that considers language as the final
      product of the well-synchronized functioning of parallel distributed cortico
      subcortical networks.

PMID- 18093624
TI  - Comparison of Fick and thermodilution cardiac output determinations in standing
      horses.
AB  - The Fick and thermodilution (TD) methods are two currently popular techniques for
      determination of cardiac output (CO) in adult horses. To our knowledge, a
      comparison of these two techniques has not been reported. Six healthy, resting,
      fit, adult horses of either sex and weighing 516.5+/-33.2 kg (mean+/-SD) were
      instrumented to enable measurement of cardiac output. Resting CO was determined
      by the Fick method and by thermodilution while the horses stood quietly in the
      stocks. Fick and thermodilution CO measurements were repeated under conditions of
      increased cardiac output achieved with the use of a dobutamine infusion (5 microg
      kg(-1) min(-1), IV), and again under conditions of decreased CO induced by
      administration of xylazine (0.5 mg/kg, IV). Fick and thermodilution cardiac
      outputs were compared using Bland-Altman analysis for repeated measures. The mean
      of the differences+/-1.96SD (bias and precision) between the two techniques was
      1.88+/-24.17 L/min. Variability between measurements with the two techniques was
      decreased to 3.41+/-46.78 mL kg(-1) min(-1) when CO was normalized for body size
      by calculation of cardiac index.

PMID- 18093623
TI  - Discriminant validity and neuroanatomical correlates of rule monitoring in
      frontotemporal dementia and Alzheimer's disease.
AB  - Despite the predominant frontal neuropathology of frontotemporal dementia (FTD),
      traditional measures of executive functioning do not reliably distinguish FTD
      from Alzheimer's disease (AD). Performance monitoring is an executive function
      that is associated with frontal lobe integrity and may be disrupted in FTD. The
      current study adopted a component process approach to evaluate the discriminant
      validity and neuroanatomical correlates of performance monitoring (i.e., rule
      monitoring) during an executive spatial planning task. Forty-four participants
      with FTD, 30 with AD, and 27 healthy comparison (HC) subjects completed the Delis
      Kaplan Executive Function System (D-KEFS) Tower task. A subset of patients
      underwent structural magnetic resonance imaging to obtain regional measures of
      cortical volumes. FTD and AD groups demonstrated significantly poorer overall
      achievement scores on the Tower test relative to the HC sample, but did not
      differ from one another. In contrast, the FTD group committed significantly more
      rule violation errors than both HC and AD groups, indicating poorer performance
      monitoring. In addition, poorer overall achievement correlated with smaller brain
      volumes in several regions, including bilateral frontal and parietal regions,
      whereas an increased number of rule violations correlated specifically with
      decreased bilateral frontal volume. Both left and right frontal volumes remained
      significant predictors of rule violation errors after controlling for the
      contribution of overall achievement on the task and all other brain regions.
      Findings are consistent with literature implicating the frontal lobes in
      performance monitoring and highlight the importance of characterizing the
      component processes of performance failures in the cognitive assessment of FTD
      and AD.

PMID- 18093625
TI  - Scrapie resistance and production traits in Rambouillet rams: ram performance
      test 2002-2006.
AB  - Sheep possessing alleles for the prion protein with glutamine (Q) or histidine,
      both reported as Q, at codon 171 are highly susceptible to scrapie. Incidence of
      scrapie infection is rare when animals possess at least one allele for arginine
      (R) at codon 171. The current USDA APHIS scrapie eradication program utilizes
      genotyping for alleles that confer resistance to scrapie. Although it has not
      been a criterion of registration, genotyping has been utilized in the University
      of Wyoming Ram Performance test since 2002. Performance test records from 2002 to
      2006 (n=518) were analyzed to determine if any production loss or benefit was
      associated with scrapie resistance in rams. Performance of rams with scrapie
      resistant genotypes was equal to or better than scrapie susceptible rams. Based
      on test performance as an acceptable indicator of sire superiority, selection for
      rams with scrapie resistant genotypes should not negatively impact flock
      performance.

PMID- 18093626
TI  - [Osirix: free and open-source software for medical imagery].
AB  - Osirix is a tool for diagnostic imagery, teaching and research tasks, which
      presents many possible applications in maxillofacial and oral surgery. It is a
      free and open-source software developed on Mac OS X (Apple) by Dr Antoine Rosset
      and Dr Osman Ratib, in the department of radiology and medical computing of
      Geneva (Switzerland).

PMID- 18093627
TI  - Real-time multiplex PCR assay for detection and differentiation of rickettsiae
      and orientiae.
AB  - The high incidence of rickettsial diseases in Southeast Asia necessitates rapid
      and accurate diagnostic tools for a broad range of rickettsial agents, including
      Orientia tsutsugamushi (scrub typhus) and Rickettsia typhi (murine typhus), but
      also spotted fever group infections, which are increasingly reported. We present
      an SYBR-Green-based, real-time multiplex PCR assay for rapid identification and
      differentiation of scrub typhus group, typhus group and spotted fever group
      rickettsiae using 47kDa, gltA and ompB gene targets. Detection limits for
      amplification of these genes in reference strains ranged from 24 copies/microl, 5
      copies/microl and 1 copy/microl in multiplex and 2 copies/microl, 1 copy/microl
      and 1 copy/microl in single template format, respectively. Differentiation by
      melt-curve analysis led to distinct melt temperatures for each group-specific
      amplicon. The assay was subjected to 54 samples, of which all cell-culture and
      75% of characterised clinical buffy coat samples were correctly identified. Real
      time PCR has the advantage of reliably detecting and differentiating rickettsial
      and orientia cell-culture isolates in a single-template assay, compared with the
      more time-consuming and laborious immunofluorescence assay. However, further
      optimisation and validation on samples taken directly from patients to assess its
      clinical diagnostic utility is required.

PMID- 18093628
TI  - The north Indian dengue outbreak 2006: a retrospective analysis of intensive care
      unit admissions in a tertiary care hospital.
AB  - Dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome
      (DSS) have emerged as public health problems of international concern. During a
      dengue outbreak in north India in October 2006, more than 10000 patients
      presented to hospital with fever. We retrospectively analysed the presenting
      features, treatment given and the outcome of patients admitted to the Intensive
      Care Unit (ICU), All India Institute of Medical Sciences (AIIMS): a tertiary care
      hospital in New Delhi. A total of 72 critically ill patients were referred for
      admission to the ICU. The common symptoms were fever (100%), myalgia (40%) and
      gastrointestinal bleed. Menorrhagia and haematuria were seen as the sole
      presenting features in many females. Treatment consisted of bed rest, oxygen
      therapy, intensive monitoring, antipyretics, platelet transfusions, hydration and
      electrolyte correction. On average, six units of platelets were required per
      patient. The average duration of stay in the ICU was 3 d. There were eight
      deaths. Adequate hydration and platelet replacement with transfusions, especially
      apheresis platelets to a target level above 60000 platelets/mm3, were effective
      means of combating the disease.

PMID- 18093630
TI  - Unique effect of the pregnancy hormone estriol on antigen-induced production of
      specific antibodies in female BALB/c mice.
AB  - We investigated the modulatory effect of estriol (E(3)), an estrogen
      predominantly produced during human pregnancy, on the antigen-induced production
      of specific antibodies in female BALB/c mice, and its effect was compared with
      17beta-estradiol (E(2)). Estriol (E(3)) had a very different effect than E(2) on
      the antigen-induced production of specific antibodies in animals immunized with
      two different antigens, i.e., the bovine serum albumin (BSA) and pneumococcal
      polysaccharide serotype-14 (PPS-14). While E(2) strongly stimulated the
      production of BSA-specific antibodies (mostly IgG1), E(3) had little or no effect
      on their production. In comparison, when the bacterial PPS-14 was the immunogen,
      E(3) and E(2) both strongly increased the production of PPS-14-specific
      antibodies (mostly IgM). E(3) and E(2) also had a similar effect on the thymus
      weight reduction and on the spontaneous antibody production in these animals. Our
      results provided an example demonstrating that the pregnancy hormone E(3) has a
      distinctly different profile of modulatory actions in the immune system compared
      to E(2), while the former strongly enhanced the body's ability to produce
      bacteria-specific IgM antibodies, it had no effect on the production of specific
      antibodies against a soluble protein. This differential effect of E(3) may be
      beneficial for reducing the risk of developing antibody-mediated immune attack
      against the maternal and fetal elements during pregnancy.

PMID- 18093631
TI  - Oxygenation and gender effects on photopic frequency-doubled contrast
      sensitivity.
AB  - Thresholds to a temporally modulated contrast stimulus were examined across the
      central visual field, at photopic luminance (100 cd m(-2)), under aviation
      related respiratory disturbances. These were mild hypoxia (14.1% oxygen),
      hyperoxia (100% oxygen), and hypocapnia (voluntary hyperventilation), with
      control exposures breathing air at rest. Thresholds were analysed by retinal
      eccentricity and by visual field quadrant. Hypoxia compromised sensitivity away
      from fixation (p<.001). Gender differences in sensitivity were apparent over the
      nasal hemifield and in response to 100% oxygen. An unexpected and highly
      statistically significant effect of oxygen tension (PO2) exposure order (p<.001)
      implies the existence of short-term retinal 'memory' for recent PO2.

PMID- 18093629
TI  - The role of estrogens and estrogen receptors in normal prostate growth and
      disease.
AB  - Estrogens have significant direct and indirect effects on prostate gland
      development and homeostasis and have been long suspected in playing a role in the
      etiology of prostatic diseases. Direct effects are mediated through prostatic
      estrogen receptors alpha (ERalpha) and beta (ERbeta) with expression levels
      changing over time and with disease progression. The present review examines the
      evidence for a role of estrogens and specific estrogen receptors in prostate
      growth, differentiation and disease states including prostatitis, benign
      prostatic hyperplasia (BPH) and cancer and discusses potential therapeutic
      strategies for growth regulation via these pathways.

PMID- 18093632
TI  - Contour integration by 6-month-old infants: discrimination of distinct contour
      shapes.
AB  - Previous research has indicated that the ability to integrate individual elements
      in the presence of noise is immature in 3-month-old infants. The present study
      extended the developmental timeline by investigating 6-month-olds' ability to
      integrate individual elements into whole contours through an assessment of their
      capability to discriminate circle and square contours constructed from oriented
      Gabor patches via a newly designed cueing paradigm for infants. If infants
      discriminate the centrally-presented contour cues, then their eye movements would
      correctly anticipate subsequent target presentation at a rate greater than
      chance. The results indicated that infants integrated the contours and
      discriminated the different shapes, but, consistent with past research, this
      ability is still fairly immature at this age, tolerating limited amount of noise.

PMID- 18093633
TI  - Reaction of chlorine dioxide with emergent water pollutants: product study of the
      reaction of three beta-lactam antibiotics with ClO(2).
AB  - This work deals with the chlorine dioxide (ClO(2)) reactivity with three
      representative beta-lactam antibiotics (penicillin, amoxicillin and cefadroxil)
      that can be present in natural aquatic resources. Due to the wide use of ClO(2)
      as disinfection agent our work is of interest to determine the fate of these
      antibiotics during the water treatment process. Our study shows that antibiotics
      react stoichiometrically with ClO(2) because increasing amounts of ClO(2) lead to
      increasing antibiotic disappearance. Concerning the influence of antibiotic
      structure, penicillin reacts sluggishly with ClO(2), whereas amoxicillin and
      cefadroxil are highly reactive at either neutral or basic pH. For both reactive
      antibiotics, hydroquinone together with a wide range of 4-substituted phenols
      were detected as products. Pretreatment with ClO(2) before chlorination of
      aqueous solutions of antibiotics reduces the trihalomethane formation as compared
      with analogous chlorination without ClO(2) pretreatment.

PMID- 18093634
TI  - Fungicidal values of bio-oils and their lignin-rich fractions obtained from
      wood/bark fast pyrolysis.
AB  - Pine wood, pine bark, oak wood and oak bark were pyrolyzed in an auger reactor. A
      total of 16 bio-oils or pyrolytic oils were generated at different temperatures
      and residence times. Two additional pine bio-oils were produced at the National
      Renewable Energy Laboratory in a fluidized-bed reactor at different temperatures.
      All these bio-oils were fractionated to obtain lignin-rich fractions which
      consist mainly of phenols and neutrals. The pyrolytic lignin-rich fractions were
      obtained by liquid-liquid extraction. Whole bio-oils and their lignin-rich
      fractions were studied as potential environmentally benign wood preservatives to
      replace metal-based CCA and copper systems that have raised environmental
      concerns. Each bio-oil and several lignin-rich fractions were tested for
      antifungal properties. Soil block tests were conducted using one brown-rot fungus
      (Gloeophyllum trabeum) and one white-rot fungus (Trametes versicolor). The lignin
      rich fractions showed greater fungal inhibition than whole bio-oils for a
      impregnation solution 10% concentration level. Water repellence tests were also
      performed to study wood wafer swelling behavior before and after bio-oil and
      lignin-rich fraction treatments. In this case, bio-oil fractions did not exhibit
      higher water repellency than whole bio-oils. Comparison of raw bio-oils in soil
      block tests, with unleached wafers, at 10% and 25% bio-oil impregnation solution
      concentration levels showed excellent wood preservation properties at the 25%
      level. The good performance of raw bio-oils at higher loading levels suggests
      that fractionation to generate lignin-rich fractions is unnecessary. At this more
      effective 25% loading level in general, the raw bio-oils performed similarly.
      Prevention of leaching is critically important for both raw bio-oils and their
      fractions to provide decay resistance. Initial tests of a polymerization chemical
      to prevent leaching showed some success.

PMID- 18093635
TI  - Photocatalytic degradation of lignin using Pt/TiO2 as the catalyst.
AB  - Photocatalytic degradation of lignin was studied with the use of catalysts TiO(2)
      and Pt/TiO(2). The influence of several experimental parameters, i.e. pH,
      catalyst dosage and illumination on lignin degradation was investigated. The
      results showed that application of UV irradiation alone has almost no effect on
      the reduction of dissolved organic carbon (DOC) and American Dye Manufacture
      Institute value (ADMI). However, the addition of TiO(2) and Pt/TiO(2) reduced the
      original DOC (251 mg l(-1)) by more than 40% within 30 min of treatment and the
      reaction can be simulated with pseudo-first order kinetics. Rapid degradation of
      lignin was observed in acidic solution using either TiO(2) or Pt/TiO(2) as the
      catalyst compared to high pH cases. The content of Pt in the Pt/TiO(2) catalyst
      is 1%. In addition, too much catalyst addition has not increased the DOC and ADMI
      reduction proportionally. The investigation also indicated that the
      photocatalytic degradation rates could be enhanced 1-6 times faster after doping
      TiO(2) with Pt in different pH cases. A modified Nernst type model was adopted to
      simulate the decoloring process using TiO(2) and Pt/TiO(2) based on the profiles
      of oxidation reduction potential during the photocatalytic reaction. The
      developed equation can be used to predict the color removal efficiency of lignin
      wastewater by the photocatalytic process.

PMID- 18093636
TI  - On the thermally induced isomerisation of hexabromocyclododecane stereoisomers.
AB  - The interconversion of the stereoisomers contained in technical 1,2,5,6,9,10
      hexabromocyclododecane, a major brominated flame retardant increasingly found in
      the environment and in biota, was investigated at elevated temperatures. The
      application of pure enantiomers of the three constituents alpha-, beta-, and
      gamma-HBCD enabled the unambiguous elucidation of the individual isomerisation
      reactions as well as the quantification of all respective rate constants. At 160
      degrees C the rate constants range over two orders of magnitude from 1.50x10(-3)
      to 1.88x10(-5)mol(%)s(-1). A preliminary mechanistic explanation for the
      differences of the rate constants which govern the composition of HBCD
      diastereomers at equilibrium is given.

PMID- 18093637
TI  - Two strategies of clopidogrel loading dose to decrease the frequency of
      clopidogrel resistance in patients undergoing percutaneous coronary intervention.

PMID- 18093639
TI  - Effective practices for school-based tobacco use prevention.
AB  - BACKGROUND: Research evidence addressing effectiveness of tobacco use prevention
      interventions has accumulated since the 1970s. Systematic reviews 1985-2006 were
      considered, building on previous syntheses and spanning tobacco control and
      prevention efforts to date. Practitioners' experience was drawn upon to
      supplement research evidence. METHODS: A systematic, comprehensive approach was
      used to synthesize published literature evaluating the effectiveness of school
      based tobacco use prevention interventions. Systematic reviews conducted on all
      populations published in English, peer-reviewed journals were included. Reviews
      were screened for relevance and assessed for methodological quality using pre
      tested, standardized tools. The best available evidence was extracted and
      integrated with experiential evidence from individual interview and focus group
      results from practitioners involved in tobacco use prevention programming.
      RESULTS: Considerable consensus among the three evidence sources indicates that
      school-based tobacco use prevention interventions are effective in reducing
      smoking prevalence, reducing smoking initiation and intended smoking intentions
      in the short term. There is adequate evidence from over three decades of research
      and years of experience to recommend ongoing implementation of school-based
      tobacco use prevention interventions. CONCLUSION: There is strong evidence that
      school-based tobacco use prevention programs are largely effective for most
      tobacco use related outcomes, at least in the short term.

PMID- 18093640
TI  - Existence of an electrically insulating layer in amalgam-containing galvanic
      couples.
AB  - OBJECTIVE: Avoiding the placement of amalgam and noble metal restorations in
      interproximal contact is recommended due to anticipated galvanic corrosion of the
      amalgam. There is a similar concern for amalgam/amalgam galvanic couples. It was
      the objective of this study to determine if an electrically insulating layer
      forms in the contact area of these galvanic couples. The existence of an
      electrically insulating layer, which could reduce the galvanic corrosion rate,
      would be indicated by different corrosion potentials for the two restorations of
      the couple. METHODS: Using a convenience sample of 158 human subjects, corrosion
      potentials were measured on each restoration of three types of galvanic couples:
      amalgam/noble metal (n=8), amalgam/amalgam (n=93) and noble metal/noble metal
      (n=7). Measurements were made with a Ag/AgCl micro-reference electrode and a high
      impedance voltmeter. All restorations were at least 6 months old. RESULTS:
      Statistical analysis showed that the mean absolute corrosion potential
      differences and the simultaneous confidence intervals of the couples were,
      respectively, amalgam/noble metal: 62 (31)mV and (27, 99)mV, amalgam/amalgam: 11
      (14)mV and (7, 15)mV and noble metal/noble metal: 7 (10)mV and (0, 19)mV.
      SIGNIFICANCE: The amalgam/noble metal couples had consistent and mostly large
      corrosion potential differences between their restorations, which indicated the
      presence of an electrically insulating layer. An electrically insulating layer
      was also indicated for the amalgam/amalgam and noble metal/noble metal couples.
      The layer is probably composed of non-metallic corrosion products, biofilms, and
      possibly, dental calculus, which could reduce galvanic corrosion rates to small
      or negligible values.

PMID- 18093638
TI  - Non-genomic actions of androgens.
AB  - Previous work in the endocrine and neuroendocrine fields has viewed the androgen
      receptor (AR) as a transcription factor activated by testosterone or one of its
      many metabolites. The bound AR acts as transcription regulatory element by
      binding to specific DNA response elements in target gene promoters, causing
      activation or repression of transcription and subsequently protein synthesis.
      Over the past two decades evidence at the cellular and organismal level has
      accumulated to implicate rapid responses to androgens, dependent or independent
      of the AR. Androgen's rapid time course of action; its effects in the absence or
      inhibition of the cellular machinery necessary for transcription/translation; and
      in the absence of translocation to the nucleus suggest a method of androgen
      action not initially dependent on genomic mechanisms (i.e. non-genomic in
      nature). In the present paper, the non-genomic effects of androgens are reviewed,
      along with a discussion of the possible role non-genomic androgen actions have on
      animal physiology and behavior.

PMID- 18093641
TI  - Correlation between ceramics translucency and polymerization efficiency through
      ceramics.
AB  - OBJECTIVES: The aim of this study was to analyse the effects of curing with a
      high intensity curing unit for different exposure times, for different ceramic
      types, thicknesses and corresponding different ceramic translucencies. The
      relationship between ceramic translucency and hardness, as well as the critical
      translucency value for sufficient curing were also determined. METHODS: All these
      effects were expressed in terms of Vickers hardness measured with an automatic
      micro hardness indenter on thin luting composite films (Variolink II), stored for
      24h in distilled water at 37 degrees C. Two preliminary studies determined the
      time necessary to achieve maximum hardness in the luting composite, with and
      without an additional chemical catalyst. The main study aimed to estimate the
      effect on luting composite hardness, without an additional chemical catalyst, of
      the following parameters: curing time (5, 10 and 15s), ceramic thickness (0.5, 1,
      2 and 3mm), ceramic type (two leucite-reinforced and two lithium disilicate glass
      ceramics) and ceramic translucency (TP), measured using a reflection
      spectrophotometer as a function of wavelength. RESULTS: The minimum curing time
      necessary to achieve maximum hardness in the luting composite was 15s for both
      groups, with and without an additional chemical catalyst. However, dual curing
      caused a hardness enhancement of ca. 50%. The two leucite-reinforced glass
      ceramics did not reduced the hardness of the luting composite up to a ceramic
      thickness of 2mm, whereas the more dense lithium disilicate glass-ceramics had
      already caused this effect at a thickness of 1mm. ANOVA analyses revealed that
      the greatest effect on the luting composite hardness resulted from the curing
      time (eta square=0.62) followed by translucency (eta square=0.32 TP650 nm and
      0.28 for TP470 nm), ceramic type (eta square=0.17) and ceramic thickness (eta
      square=0.03). SIGNIFICANCE: High-power curing units are not able to consistently
      reduce the exposure time. In both systems, at least 15s were necessary to
      properly cure the luting composite. Furthermore, the effect of light activation
      on the dual curing luting composite cannot be neglected.

PMID- 18093642
TI  - Patterns of interaction in adolescent romantic relationships: Distinct features
      and links to other close relationships.
AB  - This study examined the similarities and differences between adolescents'
      interactions with romantic partners and those with friends and mothers. Thirty
      two adolescents were observed interacting with a romantic partner, a close
      friend, and their mother. Adolescents and romantic partners engaged in more
      conflict than adolescents and friends. Adolescents' affective responsiveness was
      less positive with romantic partners than with their friends. Additionally, the
      dyadic positivity was lower in romantic relationships than in friendships. More
      off-task behavior occurred in romantic relationships than in mother-adolescent
      relationships. Romantic partners were also less skillful communicators and had
      lower levels of affective responsiveness than mothers. Adolescents perceived more
      support and fewer negative interactions in romantic relationships than in
      relationships with mothers. Consistent with expectations, adolescents'
      interactions with romantic partners were associated with those with friends and
      mothers. Thus, romantic relationships are characterized by distinct patterns of
      interaction, yet also are associated with other close relationships.

PMID- 18093643
TI  - Latitudinal distribution of mesozooplankton in the off-equatorial northeastern
      Pacific before and after the 1998/99 La Nina event.
AB  - Factors affecting mesozooplankton distributions in the northeastern tropical
      Pacific Ocean were investigated using data obtained along a meridian line (5
      degrees -12 degrees N, 131.5 degrees W) in the summers of 1998, 1999, and 2003.
      The survey periods corresponded to a sharp transition between the 1997-1998 El
      Nino and 1998-1999 La Nina events, the 1999 La Nina event, and near-normal
      conditions after the moderate 2002-2003 El Nino in the equatorial Pacific. A
      strong upwelling in the divergence zone from 10.5 degrees to 11 degrees N caused
      a shoaling of the thermocline depth (approximately 30 m), resulting in increases
      in nitrate and phytoplankton chlorophyll a (chl-a) concentrations, and, in turn,
      mesozooplankton abundance during the La Nina in 1999. In contrast, in 1998,
      remnants of El Nino characteristics, deeper thermocline depth (60-150 m) and warm
      surface water (>28 degrees C), led to low concentrations of nitrate, chl-a and
      low mesozooplankton abundance, except in the convergence zone around 7 degrees N.
      The thermocline depth and nitrate concentration obtained during the near-normal
      period in 2003 corresponded to intermediate values as compared to those obtained
      during El Nino and La Nina conditions. Interannual changes in the position and
      strength of ecotones, such as divergence and convergence zones, affected
      mesozooplankton community structure and cyclopoid-to-calanoid ratios along the
      131.5 degrees W meridian line. The clustering pattern of the mesozooplankton
      community was mostly characterized by calanoid (mainly Clausocalanus sp.) and
      cyclopoid (mainly Oncaea sp.) copepods, accounting for most of the observed
      differences among groups during the study period. Cyclopoids and calanoids were
      more abundant in 1999 than in 1998 or 2003, with a sharp increase to the north,
      while they were less abundant to the north in 1998 and 2003. The cyclopoid-to
      calanoid ratio peaked in the convergence zone in 1998 and the divergence zones in
      1999 and 2003, apparently due to the strength and location of the ecotones.
      Principal component analysis (PCA) with environmental factors and dominant
      mesozooplankton groups showed that dominant groups were affected by nitrate and
      chl-a concentrations in 1998, by sigma-t (water density), nitrate and chl-a
      concentrations in 1999, and by sigma-t, salinity and chl-a concentration (except
      siphonophores) in 2003. Latitudinal distribution of thermocline depth before and
      after the 1998/99 La Nina event showed a distinct interannual difference. The
      abundance of mesozooplankton in the divergence zone in 1999 was distinctively
      higher than abundances found in the convergence and divergence zones in 1998 and
      2003, which resulted from the shallow thermocline depth due to an intensified
      upwelling during the strong 1998-1999 La Nina event.

PMID- 18093644
TI  - Experimental and theoretical characterization of implantable neural
      microelectrodes modified with conducting polymer nanotubes.
AB  - Neural prostheses transduce bioelectric signals to electronic signals at the
      interface between neural tissue and neural microelectrodes. A low impedance
      electrode-tissue interface is important for the quality of signal during
      recording as well as quantity of applied charge density during stimulation.
      However, neural microelectrode sites exhibit high impedance because of their
      small geometric surface area. Here we analyze nanostructured-conducting polymers
      that can be used to significantly decrease the impedance of microelectrode
      typically by about two orders of magnitude and increase the charge transfer
      capacity of microelectrodes by three orders of magnitude. In this study
      poly(pyrrole) (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT) nanotubes were
      electrochemically polymerized on the surface of neural microelectrode sites (1250
      microm(2)). An equivalent circuit model comprising a coating capacitance in
      parallel with a pore resistance and interface impedance in series was developed
      and fitted to experimental results to characterize the physical and electrical
      properties of the interface. To confirm that the fitting parameters correlate
      with physical quantities of interface, theoretical equations were used to
      calculate the parameter values thereby validating the proposed model. Finally, an
      apparent diffusion coefficient was calculated for PPy film (29.2+/-1.1 x 10(-6)
      cm(2)/s), PPy nanotubes (PPy NTs) (72.4+/-3.3 x 10(-6) cm(2)/s), PEDOT film
      (7.4+/-2.1 x 10(-6) cm(2)/s), and PEDOT nanotubes (PEDOT NTs) (13.0+/-1.8 x 10(
      6) cm(2)/s). The apparent diffusion coefficient of conducting polymer nanotubes
      was larger than the corresponding conducting polymer films.

PMID- 18093645
TI  - Osteogenicity of biphasic calcium phosphate ceramics and bone autograft in a goat
      model.
AB  - The aim of this work was to compare the osteogenicity of calcium phosphate
      ceramic granules with autologous bone graft in ectopic and orthotopic sites.
      Biphasic calcium phosphate (BCP) granules composed of hydroxyapatite (HA) and
      beta-tricalcium phosphate (beta-TCP) in a 60/40 ratio were sintered at 1050, 1125
      and 1200 degrees C, producing different microporosities. Either BCP ceramic
      granules or autologous bone chips (n=7) were implanted into paraspinal muscles.
      Osteoinduction was not observed in either the BCP implants or autologous bone
      chips after 6 or 12 weeks in the ectopic sites. Hollow and bored
      polytetrafluoroethylene (PTFE) cylinders were filled with autologous bone, BCP
      granules or left empty, then implanted into critical-sized defects in femoral
      epiphyses. The PTFE cylinders left empty contained marrow and blood vessels but
      not mineralized bone, indicating that this model prevented bone ingrowth (0.56+/
      0.43% at 12 weeks). Bone formation was observed in contact with the BCP1050 and
      BCP1125 granules in the femoral sites after 6 weeks. The amount of bone after 12
      weeks was 5.6+/-7.3 and 9.6+/-6.6% for BCP1050 and BCP1125, respectively. Very
      little bone formation was observed with the BCP1200 implants (1.5+/-1.3% at 12
      weeks). In both the ectopic and orthotopic sites, autologous bone chips were
      drastically resorbed (from 19.4+/-3.7% initially to 1.7+/-1.2% at 12 weeks). This
      study shows that synthetic bone substitutes may have superior stability and
      osteogenic properties than autologous bone grafts in critical-sized bone defects.

PMID- 18093646
TI  - Pharmacokinetics, biodistribution, efficacy and safety of N-octyl-O-sulfate
      chitosan micelles loaded with paclitaxel.
AB  - Paclitaxel (Taxol), PTX) is a promising anti-cancer drug and has been
      successfully used to treat a wide variety of cancers. Unfortunately, serious
      clinical side effects are associated with it, which are caused by PTX itself and
      non-aqueous vehicle containing Cremophor EL. Development of new formulation of
      PTX with better efficacy and fewer side effects is extremely urgent. In the
      present study, a N-octyl-O-sulfate chitosan (NOSC) micelle was developed and used
      as the delivery system for PTX. The pharmacokinetics, biodistribution, efficacy
      and safety of PTX-loaded NOSC micelles (PTX-M) were evaluated. The results showed
      that NOSC micelles had high drug loading capacity (69.9%) and entrapment
      efficiency (97.26%). The plasma AUC of PTX-M was 3.6-fold lower than that of
      Taxol; but the V(d) and CL of PTX-M were increased by 5.7 and 3.5-fold,
      respectively. Biodistribution study indicated that most of the PTX were
      distributed in liver, kidney, spleen, and lung and the longest retention effect
      was observed in the lung. Drug safety assessment studies including acute
      toxicity, hemolysis test, intravenous stimulation and injection anaphylaxis
      revealed that the PTX-M was safe for intravenous injection. Furthermore, the
      comparable antitumor efficacy of PTX-M and Taxol was observed at the same dose of
      10 mg/kg in in vivo antitumor mice models inoculated with sarcoma180, enrich
      solid carcinoma (EC), hepatoma solidity (Heps), Lewis lung cancer cells and A-549
      human lung cancer cells. These results clearly showed that PTX-M had the similar
      antitumor efficacy as Taxol, but significantly reduced the toxicity and improved
      the bioavailability of PTX.

PMID- 18093647
TI  - Placenta: platform for life. Proceedings of the International Federation of
      Placenta Associations Meeting 2007. August 17-21, 2007. Kingston, Ontario,
      Canada.

PMID- 18093649
TI  - Small peptides mimicking substance P (1-7) and encompassing a C-terminal amide
      functionality.
AB  - Some of the biological effects demonstrated after administration of substance P
      (SP) in vivo can indirectly be attributed to the fragmentation of the
      undecapeptide to its N-terminal bioactive fragment SP(1-7). This heptapeptide (H
      Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH) is a major bioactive metabolite from SP that
      frequently exerts similar biological effects as the parent peptide but also, in
      several cases, completely opposite actions. Specific binding sites for the
      heptapeptide SP(1-7) that are separate from the SP preferred NK receptors have
      been identified. In this study we demonstrate that (a) the C-terminal part of the
      SP metabolite SP(1-7) is most important for binding as deduced from an Ala scan
      and that a replacement of Phe(7) for Ala is deleterious, (b) truncation of the N
      terminal amino acid residues of SP(1-7) delivers peptides with retained binding
      activity, although with somewhat lower binding affinities than SP(1-7) and (c) a
      C-terminal amide group as a replacement for the terminal carboxy group of SP(1-7)
      and for all of the truncated ligands synthesized affords approximately 5-10-fold
      improvements of the binding affinities.

PMID- 18093648
TI  - Uric acid as a pathogenic factor in preeclampsia.
AB  - Hyperuricemia is a common finding in preeclamptic pregnancies evident from early
      pregnancy. Despite the fact that elevated uric acid often pre-dates the onset of
      clinical manifestations of preeclampsia, hyperuricemia is usually considered
      secondary to altered kidney function. Increased serum uric acid is associated
      with hypertension, renal disease and adverse cardiovascular events in the non
      pregnant population and with adverse fetal outcomes in hypertensive pregnancies.
      We hypothesize that an elevated concentration of uric acid in preeclamptic women
      is not simply a marker of disease severity but rather contributes directly to the
      pathogenesis of the disorder. Using epidemiological and experimental evidence,
      gained largely outside of pregnancy, we will propose pathogenic roles for uric
      acid in preeclamptic pregnancies. Uric acid's ability to promote inflammation,
      oxidative stress and endothelial dysfunction will be highlighted with discussions
      of the potential impact on placental development and function and maternal
      vascular health.

PMID- 18093650
TI  - Two cases of acute lymphoblastic leukaemia following acute myeloid leukaemia.

PMID- 18093651
TI  - Therapy-related myelodysplastic syndrome and acute myeloid leukemia following
      treatment of acute myeloid leukemia: possible role of cytarabine.
AB  - Therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/t-AML)
      have been reported only rarely following treatment of AML. We report five
      patients treated for de novo AML who developed t-MDS/t-AML, all with chromosome 7
      abnormalities, including -7, del(7)(q22q36) and del(7)(p11.22p22). All had been
      treated with cytarabine, topoisomerase 2 inhibitors and granulocyte or
      granulocyte-monocyte colony-stimulating factor and three with alkylating agents
      as part of autologous transplant regimens. These cases further document t-MDS/t
      AML as a complication of therapy for AML. Presence of chromosome 7 abnormalities
      in patients with and without prior alkylating agent therapy suggests possible
      association with the antimetabolite cytarabine.

PMID- 18093652
TI  - Female sexual abuse and criminal justice intervention: a comparison of child
      protective service and criminal justice samples.
AB  - OBJECTIVE: The current study compared a sample of female perpetrators reported to
      Child Protective Services (CPS) to a sample of women from the criminal justice
      system. Instead of examining a clinical or criminal justice sample in isolation,
      this comparison allows a more accurate description of female sexual offending.
      METHODS: Cases were drawn from a Midwestern state's child abuse registry, law
      enforcement records, and sex offender registry. The CPS sample consisted of 179
      women, and the criminal justice system sample consisted of 57 women. All cases
      were reported to the agencies between 1994 and 2004. RESULTS: Victims ranged in
      age from 1 to 18 years old (M=9.98, SD=4.37). As hypothesized, there were
      statistically significant differences between the CPS and criminal justice
      samples. Specifically, the CPS sample had a majority of victims under age 12
      (74.9%), while the criminal justice sample had a majority of victims between ages
      13 and 19 (73.8%). The CPS sample had predominantly intrafamilial victims
      (97.8%), while the criminal justice sample had a majority of extrafamilial
      victims (63.3%). The CPS sample also showed significantly more female victims
      (63.7%), while the criminal justice sample had mostly male victims (62.1%).
      CONCLUSIONS: There were significant differences in the victim's age, the victim's
      gender and the perpetrator-victim relationship between cases managed in the CPS
      and the criminal justice system. The results highlight the need for further
      research into child welfare and law enforcement collaboration.

PMID- 18093653
TI  - In vitro leukocyte-encapsulation model in rainbow trout (Oncorhynchus mykiss).
AB  - We developed an in vitro model to study the cellular and molecular mechanisms of
      granulomatous inflammation in response to invading pathogens. Ichthyophonus
      hoferi was used as a target for encapsulation by cultivated leukocytes from the
      kidney of the rainbow trout (Oncorhynchus mykiss). The encapsulation process was
      observed over 1 week. The leukocytes were identified as either macrophages in the
      inner layer, or neutrophils and lymphocytes in the outer layer. The encapsulation
      response was inhibited by treatment with heat, but not formalin or methanol. The
      recognition of heat-unstable molecules on the pathogen surface could induce
      encapsulation. Increased expression of pro-inflammatory cytokines, such as
      interleukin (IL)-1beta, IL-8 and tumor necrosis factor-alpha2, was observed
      during encapsulation. These cytokines might play crucial roles in the
      encapsulation process. In particular, IL-8, which was expressed at a late phase,
      might recruit specific cell populations, such as the lymphocytes comprising the
      outer cellular layer around the target.

PMID- 18093654
TI  - Tandem affinity purification vectors for use in gram positive bacteria.
AB  - Tandem affinity purification has become a valuable tool for the isolation of
      protein complexes. Here we describe the construction and use of a series of
      plasmid vectors for Gram positive bacteria. The vectors utilize the SPA tag as
      well as variants containing a 3C rather than the TEV protease site as 3C protease
      has been shown to work efficiently at the low temperatures (4 degrees C) used to
      isolate protein complexes. In addition, a further vector incorporates a GST
      moiety in place of the 3xFLAG of the SPA tag which provides an additional tagging
      option for situations where SPA binding may be inefficient. The vectors are all
      compatible with previously constructed fluorescent protein fusion vectors
      enabling construction of a suite of affinity and fluorescently tagged genes using
      a single PCR product.

PMID- 18093655
TI  - Sediment microbes and biofilms increase the bioavailability of chlorpyrifos in
      Chironomus riparius (Chironomidae, Diptera).
AB  - In a microcosm study, the importance of different sources of organic matter
      (humic acids, sterile sediment, sediment, and a microbial extract) for the
      bioavailability of the hydrophobic pesticide chlorpyrifos to Chironomus riparius
      larvae was quantified. In the last two treatments biofilms were allowed to grow
      before (14)C-chlorpyrifos addition. Chlorpyrifos accumulation was quantified
      after 25 h of exposure and after 21 h of depuration. Larval accumulation was
      twice as high in the microbial extract treatment (447+/-79 microg/kg ww larvae)
      and 1.7 times higher in the sediment treatment (371+/-33 microg/kg). After
      depuration, chlorpyrifos accumulation in larval tissue showed even higher
      differences; 3.1 times higher tissue concentrations in the microbial extract
      treatment (218+/-21 microg/kg) and 2.2 times higher in the sediment treatment
      (156+/-35 microg/kg). In contrast, chlorpyrifos accumulation in the humic acid
      and sterile sediment did not differ from that in controls. These results show
      that living microbes and biofilms, by creating a microenvironment and providing
      food for larvae, markedly increase the bioavailability of chlorpyrifos to
      Chironomus riparius.

PMID- 18093656
TI  - Primary hydatid cyst of the neck.

PMID- 18093657
TI  - [What is your diagnosis? Diagnosis: Adrenomyeloneuropathy].

PMID- 18093658
TI  - Endogenous dopamine enhances the neurotoxicity of 3-nitropropionic acid in the
      striatum through the increase of mitochondrial respiratory inhibition and free
      radicals production.
AB  - 3-Nitropropionic acid (3-NP), an inhibitor of the mitochondrial enzyme succinate
      dehydrogenase, induces neuronal degeneration in the striatum. It is known that
      dopamine (DA) enhances this toxic effect. In this work, we study how the increase
      of DA influences the toxic effect of 3-NP on DAergic terminals, GABAergic
      neurons, astroglia and microglia in the striatum. We increased the content of DA
      through the inhibition of its uptake by nomifensine or the inhibition of its
      catabolism by deprenyl. We found that although nomifensine and deprenyl enhanced
      the DA overflow produced by 3-NP perfusion, they protected against the damage
      induced by 3-NP in the DAergic terminals and the GABAergic neurons in the
      striatum. Moreover, there was a decrease of apoptotic cells, astrogliosis and
      activation of microglia as index of damage. We also found that depletion of DA by
      reserpine and alpha-methyl-p-tyrosine produced a significant reduction of the
      inhibition of the respiratory rate and of the production of superoxide radical
      induced by 3-NP in synaptosomes from the striatum. All these results suggest that
      endogenous dopamine within the dopaminergic terminals of the striatum enhances
      the mitochondrial production of radical oxygen species along with the respiratory
      inhibition produced by 3-NP and thus increases the toxicity produced by 3-NP in
      the striatum.

PMID- 18093659
TI  - Sleep-stage scoring in the rat using a support vector machine.
AB  - Analysis and classification of sleep stages is a fundamental part of basic sleep
      research. Rat sleep stages are scored based on electrocorticographic (ECoG)
      signals recorded from electrodes implanted epidurally and electromyographic (EMG)
      signals from the temporalis or nuchal muscle. An automated sleep scoring system
      was developed using a support vector machine (SVM) to discriminate among waking,
      nonrapid eye movement sleep, and paradoxical sleep. Two experts scored
      retrospective data obtained from six Sprague-Dawley rodents to provide the
      training sets and subsequent comparison data used to assess the effectiveness of
      the SVM. Numerous time-domain and frequency-domain features were extracted for
      each epoch and selectively reduced using statistical analyses. The SVM kernel
      function was chosen to be a Gaussian radial basis function and kernel parameters
      were varied to examine the effectiveness of optimization methods. Tests indicated
      that a common set of features could be chosen resulted in an overall agreement
      between the automated scores and the expert consensus of greater than 96%.

PMID- 18093660
TI  - Responses of neurons in the inferior colliculus to binaural disparities: insights
      from the use of Fisher information and mutual information.
AB  - The minimal change in a stimulus property that is detectable by neurons has been
      often quantified using the receiver operating characteristic (ROC) curve, but
      recent studies introduced the use of the related Fisher information (FI). Whereas
      ROC analysis and FI quantify the information available for discriminating between
      two stimuli, global aspects of the information carried by a neuron are quantified
      by the mutual information (MI) between stimuli and responses. FI and MI have been
      shown to be related to each other when FI is large. Here the responses of neurons
      recorded in the inferior colliculus of anesthetized guinea pigs in response to
      ensembles of sounds differing in their interaural time differences (ITDs) or
      binaural correlation (BC) were analyzed. Although the FI is not uniformly large,
      there are strong relationships between MI and FI. Information-theoretic measures
      are used to demonstrate the importance of the non-Poisson statistics of these
      responses. These neurons may reflect the maximization of the MI between stimuli
      and responses under constraints on the coded stimulus range and the range of
      firing rates. Remarkably, whereas the maximization of MI, in conjunction with the
      non-Poisson statistics of the spike trains, is enough to create neurons whose ITD
      discrimination capabilities are close to the behavioral limits, the same rule
      does not achieve single-neuron BC discrimination that is as close to behavioral
      performance.

PMID- 18093661
TI  - An automatic procedure for the analysis of electric and magnetic mismatch
      negativity based on anatomical brain mapping.
AB  - Data processing techniques in electroencephalography (EEG) and
      magnetoencephalography (MEG) need user interactions. However, particularly in
      clinical applications, fast and objective data processing is important. Here we
      present an observer-independent method for EEG and MEG analysis of mismatch
      negativity (MMN) that allows reliable estimation of source activity based on
      objective anatomical references. The procedure integrates several steps including
      artifact rejection, source estimation and statistical analysis. It enables the
      evaluation of source activity in a fully automatic and unsupervised manner. To
      test its feasibility we obtained EEG and MEG responses in an auditory oddball
      paradigm in 12 healthy volunteers. The automatized method of EEG and MEG data
      analysis estimated source activity. The automatically detected MMN was closely
      comparable with the results obtained by a user-controlled method based on the
      dipole fitting. The presented workflow can be performed easily, rapidly, and
      reliably. This development may open new fields in research and clinical
      applications of source-based EEG and MEG.

PMID- 18093662
TI  - The effectiveness of carbamazepine in unipolar depression: a double-blind,
      randomized, placebo-controlled study.
AB  - Our previous studies have shown the effectiveness of carbamazepine (CBZ) in the
      treatment of bipolar depression. This double-blind, randomized, placebo
      controlled study was designed to further evaluate the efficacy of CBZ in unipolar
      depressed subjects who never received antidepressant and other psychotherapeutic
      treatment. A total of 89 patients who had at least two major depressive episodes,
      but never experienced mania or hypomania, were randomly assigned to treatment
      with immediate-release CBZ 300-800 mg/daily (n=51) or placebo (n=38) for 12
      weeks. The primary efficacy was measured using the Hamilton Rating Scale for
      Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS), and
      Clinical Global Impression-Severity (CGI-S). The mean final CBZ dose of CBZ
      treated patients was 461.6 mg/day. CBZ treatment yielded significantly greater
      improvements on the three efficacy measures at week 8 through endpoint compared
      to placebo. Patients assigned to CBZ treatment also had a significantly higher
      clinical response rate than placebo (74% vs. 42%, p<0.001), as defined for > or =
      50% reduction in HAMD score. Based on the results of our present and previous
      studies, we suggest that CBZ might be considered an alternative in the management
      of certain conditions in major depressive disorder.

PMID- 18093663
TI  - Therapeutic activity of soluble CD83: comments on Pashine et al.

PMID- 18093664
TI  - Antibodies against fetal brain in sera of mothers with autistic children.
AB  - Serum antibodies in 100 mothers of children with autistic disorder (MCAD) were
      compared to 100 age-matched mothers with unaffected children (MUC) using as
      antigenic substrates human and rodent fetal and adult brain tissues, GFAP, and
      MBP. MCAD had significantly more individuals with Western immunoblot bands at 36
      kDa in human fetal and rodent embryonic brain tissue. The density of bands was
      greater in fetal brain at 61 kDa. MCAD plus developmental regression had greater
      reactivity against human fetal brain at 36 and 39 kDa. Data support a possible
      complex association between genetic/metabolic/environmental factors and the
      placental transfer of maternal antibodies in autism.

PMID- 18093665
TI  - Nasal ganglioglioma--difficulties in radiological imaging.
AB  - Ganglioglioma is a tumour containing both astrocytic and neuronal components.
      Most gangliogliomas are observed in the brain, but may also manifest as a nasal
      glioma. Approximately 250 cases of nasal gliomas have been described in the
      literature. Gliomas are classified as heterotopias of glia tissue. In the paper
      we describe the case of nasal ganglioglioma and the diagnostic difficulties. The
      differences between ganglioglioma, nasal glioma and other congenital midline
      nasal masses are discussed.

PMID- 18093666
TI  - Ear tuberculosis: clinical and surgical treatment.
AB  - Two main points are discussed in this paper: First, the changing picture of the
      clinical process of tuberculosis, and second, various diagnostic problems caused
      by extra-pulmonary forms. We have analysed a case of ear tuberculosis in a child,
      and drawn the following conclusions: Directed chemotherapy is the primary method
      of treatment, and surgical methods should be used to provide tissue for
      bacteriological and histopathological analysis, to enable an early diagnosis
      during the first stage of the disease, and in other atypical cases.

PMID- 18093667
TI  - Development of a real-time PCR for the detection and quantitation of caprine
      herpesvirus 1 in goats.
AB  - Caprine herpesvirus 1 (CpHV-1) is an alphaherpesvirus interfering with goat
      reproductive performances. The virus is associated with neonatal mortality in
      kids and reproductive failure in adults. A real-time PCR assay based on TaqMan
      technology and targeting the gene encoding for glycoprotein C (gC) was developed
      for detection and quantitation of CpHV-1 in samples collected from infected
      goats. The detection limit of the assay was 1 x 10(2) standard DNA copies, with a
      sensitivity of 1-2 logs higher than the conventional gel-based PCR assay
      targeting the same gene. The real-time PCR was reproducible, as shown by
      satisfactory low intra-assay and interassay coefficients of variation. The
      quantitative assay was validated on clinical samples, including genital swabs and
      various tissue samples collected from goats either infected naturally or
      experimentally with CpHV-1. The high sensitivity, simplicity and reproducibility
      of the CpHV-1 fluorogenic PCR assay, combined with its wide dynamic range and
      high throughput, make this method especially suitable for studies on the
      pathogenesis and for trials with experimental vaccines and antiviral drugs.

PMID- 18093668
TI  - Treatment of hantavirus pulmonary syndrome.
AB  - Viruses in the genus Hantavirus can cause one of two serious illnesses when
      transmitted from rodents to humans: hemorrhagic fever with renal syndrome (HFRS)
      or hantavirus pulmonary syndrome (HPS). Of the two diseases, HPS is more severe
      with an approximate 40% mortality across the Americas. The high rate of mortality
      could be reduced if effective therapeutics could be discovered for treatment of
      this illness. Herein we review approaches being explored for the discovery of
      therapeutics for HPS and how they could be employed in treatment and prevention
      of disease.

PMID- 18093669
TI  - Effect of perinatal iron deficiency on myelination and associated behaviors in
      rat pups.
AB  - Iron deficiency in early development has been associated with irreversible
      alterations in brain myelination, but whether these neural changes are mirrored
      in altered behaviors in rats is not known. The goals were to determine if dietary
      induced gestational and lactational iron deficiency alters brain myelination and
      behaviors dependent on that system. Pregnant rats were randomly assigned to
      control (CN) or iron-deficient (ID) groups by providing iron-sufficient (40 ppm
      Fe) or iron-deficient (2-6 ppm Fe) diets from gestational day 5 through to
      weaning of pups. Thereafter, all offspring were fed the iron-sufficient diet. The
      myelination of subcortical white matter and the fimbria of hippocampus was
      measured by 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase, marker of
      oligodendrocyte) density at 25 days of age. Specific behavioral assessments were
      performed at multiple time points after birth. By contrast, ID rats had
      significantly lower density of CNPase in the subcortical white matter but the
      density of CNPase in fimbria of hippocampus was comparable to CN rats. Moreover,
      ID rats showed significant behavioral impairments in surface righting reflex,
      negative geotaxis reflex, vibrissae-evoked forelimb placing test and novel object
      recognition task. In conclusion, perinatal iron deficiency can significantly
      alter behavioral outcomes which may be due to delayed myelination in specific
      brain regions.

PMID- 18093670
TI  - Differential effect of three polyunsaturated aldehydes on marine bacterial
      isolates.
AB  - Bioactive polyunsaturated aldehydes (PUAs) are produced by several marine
      phytoplankton (mainly diatoms) and have been shown to have a detrimental effect
      on a wide variety of organisms, including phytoplankton and invertebrates.
      However, their potential impact on marine bacteria has been largely neglected. We
      assess here the effect of three PUAs produced by marine diatoms: 2E,4E
      decadienal, 2E,4E-octadienal and 2E,4E-heptadienal, on the growth of 33 marine
      bacterial strains, including 16 strains isolated during a bloom of the PUA
      producing diatom Skeletonema marinoi in the Northern Adriatic Sea. A
      concentration-dependent growth reduction was observed for 19 bacterial strains at
      concentrations ranging from 3 to 145 micromolL(-1). Surprisingly, Eudora
      adriatica strain MOLA358 (Flavobacteriaceae) and Alteromonas hispanica strain
      MOLA151 (Alteromonadaceae) showed growth stimulation upon exposure to PUAs at
      concentrations between 13 and 18 micromolL(-1). The remaining 12 strains were
      unaffected by even very high PUA concentrations. Strains isolated during the
      diatom bloom showed remarkable resistance to PUA exposures, with only two out of
      16 strains showing growth inhibition at PUA concentrations below 106, 130, and
      145 micromolL(-1) for 2E,4E-decadienal, 2E,4E-octadienal and 2E,4E-heptadienal,
      respectively. No correlation between taxonomical position and sensitivity to PUA
      was observed. Considering that many bacteria thrive in close vicinity of diatom
      cells, it is likely that these compounds may shape the structure of associated
      bacterial communities by representing a selection force. This is even more
      relevant during the final stages of blooms, when senescence and nutrient
      limitation increase the potential production and release of aldehydes.

PMID- 18093671
TI  - Functional status and calcaneal quantitative ultrasound measurements among the
      oldest old people living in rural areas of Korea.
AB  - The number of very elderly people is increasing worldwide, so that the prevention
      of fractures and disability in this frail population has become a growing
      concern. This study evaluated the association between functional status and bone
      health in the oldest old. The study participants were of a very elderly
      population comprising 170 rural community dwellers, aged 80-107 years.
      Quantitative ultrasound (QUS) measurements were performed on both heels.
      Functional status was assessed by evaluating activities of daily living (ADL) and
      instrumental activities of daily living (IADL). Data on sociodemographic
      characteristics and potential risk factors, including medical history, smoking,
      alcohol intake, exercise, and physical activities were collected by trained
      interviewers. Generalized multiple linear regression suggested that disability
      was significantly associated with calcaneal QUS in the oldest old. After
      adjusting for the effect of potential covariates, such as age, gender, education
      level, weight, smoking, and physical activity level, the lowest tertile score
      groups of ADL and IADL were associated with a decrease in stiffness index (SI) T
      score of calcaneal QUS. A complete ADL deficit was associated with a low QUS
      (adjusted beta vs. independent group=-1.17, 95% confidence interval=-2.01 to 
      0.33). Evidence of disability as an associated factor on bone health provides
      important insight to devise strategies for preventing or delaying further
      disablement among the elderly.

PMID- 18093672
TI  - Cerebrovascular events in left ventricular hypertrabeculation/noncompaction with
      and without myopathy.
AB  - Little is known about frequency, morphology, and causes of stroke in patients
      with left-ventricular hypertrabeculation/noncompaction (LVHT). Aim of this study
      was to find out how many LVHT-patients suffer from stroke, which abnormalities
      are found on cerebral imaging, and if stroke LVHT-patients differ from non-stroke
      LVHT-patients with regard to cardiac and neuromuscular abnormalities. METHOD AND
      MATERIALS: Records of all included patients were reviewed for stroke diagnosed
      upon history, clinical examination, or cerebral CT/MRI (CCT, cMRI). RESULTS:
      Among 104 LVHT-patients included, stroke was diagnosed in 16 (15%). Of these two
      had a transitory ischemic attack and one a prolonged ischemic deficit. Among 36
      patients undergoing a CCT (n=32), cMRI (n=9), or both (n=5) territorial stroke
      was found in 7, lacunar stroke in 2, and intracerebral bleeding in 1. Other
      imaging findings were atrophy (n=7), microangiopathy (n=4), leucencephalopathy
      (n=3), basal-ganglia-calcification (n=2), or non-specific hypodensities (n=2).
      Imaging studies without vascular lesions were found in 2 patients. At least one
      classical risk factor for stroke was found in 15 patients. Stroke-patients did
      not differ from non-stroke-patients regarding cardiac or neuromuscular findings.
      CONCLUSIONS: If systematically looked for, stroke is a frequent feature of LVHT.
      A causal relation between LVHT and stroke, however, is rather the exception than
      the rule.

PMID- 18093673
TI  - HITT and stent thrombosis: a "clinical" diagnosis not to be missed.
AB  - Heparin induced thrombocytopenia and thrombosis (HITT) syndrome is a rare but
      potentially life threatening disorder, which is increasingly recognized with the
      widespread use of heparin. We report a rare case of early stent thrombosis
      secondary to HITT in a patient initially presenting with cardiogenic shock, which
      occurred 9 days after primary bare metal stent implantation due to subcutaneous
      heparin exposure. The most important factor in detection of HITT remains a high
      index of clinical suspicion and close monitoring of the temporal trend of
      thrombocytopenia, particularly when trying to distinguish HITT from other sources
      of thrombocytopenia seen in critically ill patients.

PMID- 18093674
TI  - Short-course preoperative radiotherapy with delayed surgery in rectal cancer - a
      retrospective study.
AB  - PURPOSE: In the most advanced, non-resectable primary rectal cancers,
      conventional long-course radiotherapy (RT) (1.8-2Gyx25-28), frequently combined
      with chemotherapy, has been used since tumour regression is needed in order to
      allow a radical (R0) resection. In Uppsala, short-course 5x5Gy with planned
      delayed surgery has been used in patients with contraindications to long-course
      RT (+/-chemotherapy). The aim is to describe our experience of using this
      approach in patients not eligible for standard treatment. PATIENTS AND METHODS:
      During 2002 and 2005, 46 patients with non-resectable rectal cancer (+/
      synchronous distant metastases) were treated with 5x5Gy and delayed surgery if
      possible. The clinical records were retrospectively evaluated. The first group
      (A) had no metastases (T4NXM0), whereas the other two groups (B+C) had metastases
      (T4NXM1). In group (B), the patients had predominantly loco-regional disease and
      were not candidates for combination chemotherapy (high age, co-morbidities), and
      in group (C) up-front combination chemotherapy was given, with the intention to
      have surgery of both the primary and the secondaries if sufficient regression at
      both sites were seen. RESULTS: The patients in the first two groups (A+B) were
      old (median 79 and 76 years, respectively), and had several co-morbidities. In
      group (C), median age was 63 years. The 5x5Gy RT was well tolerated by most
      patients, but grade IV diarrhoea was recorded in three elderly patients. One
      patient in the group (C) died from neutropenic fever. Many patients were reported
      to have less local symptoms after the treatment given. Delayed surgery was
      performed in all but nine patients. Radical surgery (R0+R1) was performed in 22
      (92%) (group A), 4 (44%) (group B), and 6 (46%) (group C) patients, respectively.
      A pCR was seen in four patients (two in group A and two in group C). No
      postoperative deaths occurred. CONCLUSIONS: Considering the very high age and
      presence of co-morbidity, the 5x5Gy schedule is well tolerated. Further,
      considering the very advanced local stage, the schedule has considerable anti
      tumour activity and can result in radical surgery in a high proportion of
      patients.

PMID- 18093675
TI  - Quantitative EEG in early Alzheimer's disease patients - power spectrum and
      complexity features.
AB  - The goal of this study was to investigate the EEG signs of early stage
      Alzheimer's disease (AD) by conventional analyses and by methods quantifying
      linear and nonlinear EEG-complexity. The EEG was recorded in 12 mild AD patients
      and in an age-matched healthy control group (24 subjects) in both eyes open and
      eyes closed conditions. Frequency spectra, Omega-complexity and Synchronization
      likelihood were calculated on the data. In the patients a significant decrease of
      the relative alpha and increase of the theta power were found. Remarkably
      increased Omega-complexity and lower Synchronization likelihood were observed in
      AD in the 0.5-25 Hz frequency ranges. It is concluded that both spectral- and EEG
      complexity changes can be found already in the early stage of AD in a wide
      frequency range. Application of conventional EEG analysis methods in combination
      with quantification of EEG-complexity may improve the chances of early diagnosis
      of AD.

PMID- 18093676
TI  - Thalamic neural activation in the cyclophosphamide-induced visceral pain model in
      mice.
AB  - The afferent nociceptive information from the lower urinary tract terminates in
      the dorsal horn of the spinal cord, and then projects to the thalamus. In the
      present study, we examined the effects of visceral nociception from the lower
      urinary tract on the neural activity of thalamic neurons using cyclophosphamide
      (CP)-induced cystitis, a model of visceral nociception. The levels of c-fos mRNA
      as well as protein, a marker of neural activation, were investigated in the
      thalamus using in situ hybridization histochemistry and immunohistochemistry. The
      effects of pretreatment with capsaicin were also examined. In the CP-treated
      group, the c-fos mRNA as well as protein was significantly induced predominantly
      in the paraventricular area of the thalamus. The induction of c-fos mRNA
      exhibited a dose-dependency. The induction of c-fos mRNA of CP-treated mice was
      significantly inhibited by capsaicin pretreatment to deplete C-fibers. Our
      results indicate that visceral nociception from the lower urinary tract activates
      thalamic neurons and this activation is mediated in part through the activation
      of the capsaicin-sensitive C-fiber afferents. The present findings suggest that
      the levels of c-fos in the paraventricular area of the thalamus may be a useful
      marker for evaluating the afferent nerve activity from the lower urinary tract.

PMID- 18093677
TI  - Functional modification of Sendai virus by siRNA.
AB  - Sendai virus (hemagglutinating virus of Japan; HVJ) is a negative-strand RNA
      virus with robust fusion activity, and has been utilized for gene transfer and
      drug delivery. Hemagglutinin-neuraminidase (HN) protein on the viral membrane is
      important for cell fusion, but causes agglutination of red blood cells. HN
      depleted HVJ has been desired for in vivo transfection in order to improve
      safety. Here, we succeeded in producing HN-depleted HVJ using HN-specific short
      interfering RNA (siRNA). Viral production was not affected by the siRNA. HN
      protein was markedly decreased in the new HVJ, while other viral proteins were
      retained. Consequently, the hemagglutinating activity was substantially reduced
      and infection activity was suppressed. When the HN-depleted HVJ was mixed with
      cultured cells and the mixture was centrifuged for 10min at 2000xg, the modified
      HVJ recovered its infectivity to approximately 80% of wild HVJ. However,
      infectivity was abolished in the presence of anti-F antibody. Moreover,
      transfection of FITC-labeled oligodeoxynucleotides using the modified HVJ was
      also recovered by centrifugation. Thus, the HN-depleted HVJ produced using siRNA
      technology will be applicable to a delivery vector.

PMID- 18093679
TI  - Determination of the influence of the Cheneau brace on quality of life for
      adolescent with idiopathic scoliosis.
AB  - OBJECTIVE: The main objective is to determine the influence of treatment by
      Cheneau brace on the quality of life (QoL) of adolescents with idiopathic
      scoliosis. MATERIAL AND METHOD: We used the QoL scale of Climent et al. "the
      Quality of Life Profile for Spine Deformities" (QLPSD, in which a higher score
      means a worse QoL) and visual analogue scales (VAS) for pain and for QoL ranging
      from 0 to 100mm. The study includes 108 subjects divided in three groups, a
      control group of 32 patients without brace, a full-time treated group (wearing a
      Cheneau brace 23/24 hours) of 41 patients, and a part-time treated group (wearing
      the brace during the night only) of 35 patients. RESULTS: The QoL is
      significantly worse in the full-time treated group than in the group with night
      treatment and in the group without brace for the psychosocial functioning, the
      sleep disturbances, the back flexibility (P<0.001), the body image (P<0.01), as
      well as the overall score (P<0.001). On the other hand, there was no difference
      for the back pain. Among patients wearing the brace, the girls had an average
      QLPSD score higher than the boys for the psychosocial functioning, the body
      image, the overall score (P<0.05) and the back flexibility (P<0.01). Whereas
      there was no significant difference between the sexes for the sleep disturbances
      and the back pain. The QoL of patients who wear the brace was significantly
      correlated with degrees corrected wearing the brace and the patient's
      satisfaction on his or her health status. However, this correlation was very
      weak. On the other hand, there was no correlation between the quality of life and
      the age, the duration of brace treatment or the skeletal maturity (Risser sign).
      On VAS, the patients without brace have the highest score of QoL, followed the
      part-time treated patients while the full-time treated patients have the lowest
      score. CONCLUSION: The wearing of the Cheneau brace involves a significant
      reduction in the QoL whatever instruments of evaluations of QoL, QLPSD or VAS.
      The QoL of the full-time treated patients was the lowest followed part-time
      treated patients while the QoL of the patients without brace was the highest.
      However, the brace does not influence the back pain in idiopathic scoliosis at
      teenage.

PMID- 18093678
TI  - Interferon beta1-a and selective anti-5HT(2a) receptor antagonists inhibit
      infection of human glial cells by JC virus.
AB  - JC virus (JCV) is the causative agent of progressive multifocal
      leukoenchaphalopathy (PML). The disease develops when JCV gains access to the
      central nervous system, infects and destroys oligodendrocytes. The disease is
      rapidly progressing, typically fatal and no effective therapies exist to treat or
      prevent PML. The recent occurrence of PML in multiple sclerosis patients being
      treated with Avonex (IFNbeta1-a) and Tysabri (Natalizumab) and the recent reports
      linking JCV infection to the 5HT(2a) serotonin receptor led us to evaluate the
      effects of IFNbeta1-a and a panel of 5HT(2a) receptor antagonists for their
      ability to modulate virus infection. IFNbeta1-a was found to be a potent
      inhibitor of both virus infection and viral early and late gene expression. In
      addition, several 5HT(2a) receptor antagonists inhibited initial infection of
      cells by JCV but were less effective at reducing viral loads in an already
      established infection.

PMID- 18093680
TI  - The assessment and management of albuminuria in primary care.
AB  - BACKGROUND: While CKD is a common finding in patients with type 2 diabetes, the
      clinical response to its identification is often problematic. This study aims to
      determine the frequency of albuminuria in patients with type 2 diabetes in the
      primary care setting and examine the factors which influence its management.
      METHODS: Expressions of interest were invited from all registered GPs across
      Australia, from whom 500 investigators were randomly selected. Investigators were
      requested to document the clinical characteristics of 10-15 consecutively
      presenting patients with type 2 diabetes. Results from the most recent urinalysis
      were classified according to guidelines, then systematically compared to
      classifications provided by GPs themselves and their management strategies.
      RESULTS: One in three patients had an elevated urinary albumin excretion (UAE,
      34.6%, 95% CI, 33.3-35.9%) on their most recent urinalysis. The presence of
      microalbuminuria or proteinuria, as identified by the GP, was not associated with
      a perceived increase in cardiovascular risk. In addition, the use of aspirin and
      the prescribing of agents to block the RAS were not significantly linked to UAE.
      Similarly, the perceived adequacy of blood pressure control was not significantly
      different whether or not microalbuminuria or proteinuria was identified to be
      present. CONCLUSION: An elevated UAE is a common finding in general practice.
      However, it fails to significantly influence their clinical care. Additional
      education to ensure appropriate case recognition and management of kidney disease
      is needed, focusing on the significance of albuminuria to the care of patients
      with type 2 diabetes.

PMID- 18093681
TI  - High glucose increases phosphocofilin via phosphorylation of LIM kinase due to
      Rho/Rho kinase activation in cultured pig proximal tubular epithelial cells.
AB  - In proximal tubular epithelial cells (PTECs), depolymerization of actin by
      cofilin plays a crucial role in maintaining polarity and function. Cofilin is
      inactivated when phosphorylated by p-Lin-11/Isl-1/Mec-3 kinase (LIMK) to give p
      cofilin. LIMK is phosphorylated by phosphorylated p21-activated kinase (PAK), a
      downstream signal of phosphoinositide 3-kinase (PI3K), or by Rho kinase (ROCK),
      and is dephosphorylated by slingshot (SSH). However, in PTECs the signaling
      pathways regulating phosphorylation and dephosphorylation of cofilin, and the
      influence of high glucose (HG) on these pathways remain to be elucidated. Here,
      we show that HG in cultured porcine PTECs (LLC-PK1) increases p-cofilin and p
      LIMK1 beyond 6h and that the simultaneous presence of phlorizin reverses the
      increase. HG did not influence the levels of PI3K-p85, downstream signals to SSH1
      and p-PAK1, and mRNA of cofilin, LIMK1 and SSH1. On the other hand, wortmannin
      and LY294002 markedly increased p-cofilin and p-LIMK1 without influencing on the
      level of SSH1 protein. HG-activated RhoA and ROCK2 beyond 3h, and phlorizin
      attenuated this activation. GF109203X inhibited HG-induced increase in membranous
      RhoA and ROCK2, and phorbol ester increased these proteins. Y27632 (a ROCK
      inhibitor) reversed HG-induced increases of p-cofilin and p-LIMK1. We conclude
      that HG increases p-cofilin by phosphorylating LIMK1 through activation of
      Rho/Rho kinase, probably due to diacylglycerol-sensitive PKC activation resulting
      from increased glucose influx. HG did not alter PI3K or its downstream signals,
      even though PI3K has a physiological role in maintaining the cofilin level by
      activating SSH1.

PMID- 18093682
TI  - Endogenous heparinoids contribute to coagulopathy in patients with liver disease.

PMID- 18093683
TI  - TIPS in hereditary hemorrhagic telangiectasia: never say never.

PMID- 18093684
TI  - Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with
      NASH.
AB  - BACKGROUND/AIMS: Replacing long-chain triacylglycerols (LCT) with medium-chain
      triacylglycerols (MCT) reduces alcohol-induced liver injury. Because of the
      similarity of the pathogenesis of alcohol-induced liver damage and non-alcoholic
      steatohepatitis (NASH), our aim was to assess whether MCT is also beneficial in
      NASH. METHODS: We used a rat NASH model in which corn oil (35% of total calories)
      was isocalorically replaced with MCT. RESULTS: Partial replacement of LCT did not
      ameliorate hepatic fat accumulation, 4-hydroxynonenal, collagen type I and its
      mRNA but it increased TNF-alpha and its mRNA (p<0.001). However, in rats given
      the high-fat diet restricted to 2/3 of the amount they were consuming, these
      adverse effects decreased, with and without MCT including less liver steatosis
      and lower triacylglycerols, but without beneficial effects of MCT. When 70% of
      the fat calories were replaced with MCT with no LCT remaining in the diet, no
      steatosis developed and hepatic TNF-alpha was low. When all MCT were given with
      carbohydrates (instead of LCT) hepatic TNF-alpha also decreased (p<0.001).
      CONCLUSIONS: MCT are not hepatotoxic, provided the diet contains no significant
      amount of LCT. Total replacement of dietary LCT with MCT fed ad libitum is
      beneficial whereas partial replacement becomes hepatotoxic, unless the dietary
      intake is restricted.

PMID- 18093685
TI  - Hepatic stress in hereditary tyrosinemia type 1 (HT1) activates the AKT survival
      pathway in the fah-/- knockout mice model.
AB  - BACKGROUND/AIMS: The AKT survival pathway is involved in a wide variety of human
      cancers. We investigated the implication of this pathway in hereditary
      tyrosinemia type 1 (HT1), a metabolic disease exhibiting hepatocellular carcinoma
      (HCC), despite treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3
      cyclohexadione (NTBC) which prevents liver damage. HT1 is an autosomal recessive
      disorder caused by accumulation of toxic metabolites due to a deficiency in
      fumarylacetoacetate hydrolase (FAH), the last enzyme in the catabolism of
      tyrosine. METHODS: NTBC withdrawal in the murine fah(-/-) knockout model was used
      to analyze in vivo the correlation between pathophysiological, biochemical and
      histological features consistent with hepatocarcinogenesis and activation of the
      AKT survival pathway. RESULTS: The HT1 stress initiated by NTBC discontinuation
      causes a progressive increase of liver and kidney pathophysiology. A stable
      activation of the AKT survival pathway is observed in the liver but not in
      kidneys of fah(-/-) mice. Hepatic survival is reinforced by inhibition of
      mitochondrial-mediated apoptosis through inactivation of Bad and induction of BCl
      X(L) and BCl-2. CONCLUSIONS: The chronic stress induced by liver disease in HT1
      activates the AKT survival signal and inhibits intrinsic apoptosis to confer cell
      death resistance in vivo and favor hepatocarcinogenesis.

PMID- 18093686
TI  - Hepatic venous pressure gradient and prognosis in patients with acute variceal
      bleeding treated with pharmacologic and endoscopic therapy.
AB  - BACKGROUND/AIMS: In acute variceal bleeding (AVB) hepatic venous pressure
      gradient (HVPG) is associated with prognosis. However, this has not been studied
      in patients receiving the currently recommended therapy. We evaluate here the
      performance of early HVPG measurement as a predictor of treatment failure in
      patients with acute variceal bleeding managed with the current standard treatment
      and whether clinical variables might be of similar predictive accuracy. METHODS:
      We included 117 patients with AVB in whom HVPG was measured within 48 h of
      admission. The main endpoint was 5-day failure, a composite of uncontrolled
      bleeding, early rebleeding or death within 5 days. RESULTS: Eighteen patients
      (15%) had 5-day failure. Multivariate analysis identified three variables
      independently associated with 5-day failure: HVPG 20, systolic blood pressure at
      admission <100 mmHg and non-alcoholic cause of cirrhosis. The discriminative
      capacity of this model was good (c statistic: 0.79). When only clinical variables
      were included in the analysis, Child-Pugh class, systolic blood pressure at
      admission and etiology were the independent predictors. This model had also a
      good discriminative ability (c statistic: 0.80). CONCLUSIONS: HVPG independently
      predicts short-term prognosis in patients with acute variceal bleeding treated
      with pharmacologic and endoscopic therapy, but similar predictive accuracy can be
      achieved using only simple clinical variables that have universal applicability.

PMID- 18093687
TI  - Evaluation of a new immortalized human fetal liver cell line (cBAL111) for
      application in bioartificial liver.
AB  - BACKGROUND/AIMS: Clinical use of bioartificial livers (BAL) relies heavily on the
      development of human liver cell lines. The aim of this study was to assess the
      potential of the recently developed human fetal liver cell line cBAL111 for
      application in the AMC-BAL. METHODS: Laboratory-scale AMC-BAL bioreactors were
      loaded with 20 or 200 million cBAL111 cells and were cultured for 3 days.
      Parameters for hepatocyte-specific function and general metabolism were
      determined daily using tests with culture medium or 100% human serum. The
      bioreactors were also analyzed for mRNA levels of liver-specific genes and
      histology. RESULTS: cBAL111 eliminated ammonia at a rate up to 49% of that in
      primary porcine hepatocytes (PPH), despite a low (1.1%) urea production.
      Transcript levels of glutamine synthetase (GS) were 570% of that in human liver,
      whereas genes of the urea cycle showed low expression. GS expression was
      confirmed immunohistochemically, and glutamine was produced by the cells. cBAL111
      eliminated galactose (90.1% of PPH) and lidocaine (0.1% of PPH) and produced
      albumin (6% of PPH). Human serum did not increase function of cBAL111.
      CONCLUSIONS: cBAL111 showed liver-specific functionality when cultured inside the
      AMC-BAL and eliminated ammonia mainly by the activity of GS, and not through the
      urea cycle.

PMID- 18093689
TI  - Inflammation, HCC and sex: IL-6 in the centre of the triangle.
AB  - Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6
      production. Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M.
      Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in
      men. Similar gender disparity is seen in mice given a chemical carcinogen,
      diethylnitrosamine (DEN). DEN administration caused greater increases in serum
      interleukin-6 (IL-6) concentration in males than it did in females. Furthermore,
      ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in
      mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner
      dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also
      protected male mice from DEN-induced hepatocarcinogenesis. Estrogen inhibited
      secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced
      circulating concentrations of IL-6 in DEN-treated male mice. We propose that
      estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk
      in females, and these findings may be used to prevent HCC in males. [Abstract
      reproduced by permission of Science 2007;317:121-124].

PMID- 18093688
TI  - Origin of small hepatocyte-like progenitor in retrorsine-treated rats.

PMID- 18093690
TI  - Cross-border health activities in the Euregios: good practice for better health.
AB  - BACKGROUND: Health-related cooperation between neighbouring countries has a long
      tradition in the European Union, especially in the transfrontier structures well
      known under the label of Euregio or Euroregion. OBJECTIVE: Overview and analysis
      of cross-border health-related activities in the Euregios. METHODS: The EU-funded
      project "EUREGIO" carried out a systematic inventory analysis of cross-border
      health projects. It is based on written surveys among 53 Interreg IIIA
      secretariats, 67 Euregios and 328 project bodies. The responses of 122 health
      projects were considered. RESULTS: 37 Euregios or similar cross-border structures
      established health-relevant working groups, working circles, forums or projects.
      The cross-border health projects cover a wide spectrum of issues, e.g., education
      and training, patient care, prevention, and disaster control. Target groups were
      in most cases medical personnel, patients or decision-making bodies. Four
      official criteria for cooperation (joint project development, implementation,
      staffing and financing) are met by the great majority of projects. However, the
      survey shows a lack of information, publication and evaluation. CONCLUSIONS:
      Cross-border cooperation in health is underrepresented in many regions. The
      project results point to great potentials which should be further developed both
      in terms of quantitative and qualitative aspects. Recommendations are given for
      project actors and stakeholders.

PMID- 18093691
TI  - The soaring mechanic ventilator utilization under a universal health insurance in
      Taiwan.
AB  - OBJECTIVES: The use of mechanic ventilators (MVs) is increasing in many
      countries. Taiwan's Bureau of National Health Insurance (NHI) launched a new
      payment program in 2000 to encourage integrated care for mechanically ventilated
      patients and to reduce the heavy utilization of high-cost intensive care unit.
      This study examines the trend in MV usage in Taiwan. METHODS: This study used
      nationally representative NHI claim data from 1997 to 2004 to examine the MV
      usage. Total inpatient days and MV usage days were analyzed by piece-wise
      regression model. We also analyzed the major diagnoses related to MV dependence.
      RESULTS: While the total hospital inpatient days increased only 49.41%, MV usage
      rose 181.75% over the 8-year study period. The increase in number of MV patient
      days in ICUs has not been curbed, besides there was an increase in respiratory
      care center/wards. Acute respiratory failure (ARF), pneumonia and diabetes
      mellitus were the leading diagnoses for mechanically ventilated patients.
      CONCLUSIONS: The new NHI insurance payment program may have helped spark the
      increased trend in MV usage in Taiwan. The significant impact of insurance
      incentive on healthcare utilization is a critical issue for policymakers in
      developing healthcare programs.

PMID- 18093692
TI  - Analysis of existing methods for 3D modelling of femurs starting from two
      orthogonal images and development of a script for a commercial software package.
AB  - BACKGROUND: At present the interest in medical field about the generation of
      three-dimensional digital models of anatomical structures increases due to the
      widespread diffusion of CAS--computer assisted surgery--systems. Most of them are
      based on CT--computer tomography--or MR--magnetic resonance--data volumes but
      sometimes this information is not available; there are only few X-ray, ultrasound
      or fluoroscopic images. METHODS: This paper describes the study and the
      development of a script for a commercial software package (3ds Max) able to
      reconfigure the template model of a femur starting from two orthogonal images
      representing the specific patient's anatomy. RESULTS: The script was used in
      several tests as summarized in this paper and the results appear to be
      interesting and acceptable, even for the medical experts that evaluated them.
      CONCLUSIONS: The script developed in this work allows the generation of the 3D
      model of a femur in a very simple way (the user interface has been developed
      obeying to the main usability guidelines) and using a widespread commercial
      package. The quality of the results can be compared to the quality of more
      expensive and specialized systems.

PMID- 18093693
TI  - PTD-mediated delivery of anti-cell death proteins/peptides and therapeutic
      enzymes.
AB  - Millions of unnecessary cells are removed from our body everyday by apoptosis to
      ensure our survivals. Apoptosis is a highly coordinated process. Failure in
      apoptotic regulation results in disease. A large number of studies have
      demonstrated that accelerated apoptosis is involved in degenerative diseases,
      ischemic injuries, immunodeficiency and infertility. These studies have also
      revealed the molecular mechanisms of apoptosis signal transduction to provide
      therapeutic targets. On the other hand, protein transduction technology has been
      developed to deliver full-length proteins to various tissues including the brain.
      So far, many studies have shown that in vivo delivery of therapeutic
      proteins/peptides, including anti-apoptotic proteins, an anti-oxidant enzyme, a
      neuroprotectant, enzymes involved in purine or tyrosine metabolism, caspase
      inhibitors, c-Jun N-terminal kinase inhibitors and an NF-kappaB inhibitor, by
      protein transduction technology mitigates various diseases in animal models.

PMID- 18093694
TI  - TRAIL-induced survival and proliferation of SCLC cells is mediated by ERK and
      dependent on TRAIL-R2/DR5 expression in the absence of caspase-8.
AB  - Small cell lung cancer (SCLC) is characterized by an aggressive phenotype and
      acquired resistance to a broad spectrum of anticancer agents. TNF-related
      apoptosis-inducing ligand (TRAIL) has been considered as a promising candidate
      for safe and selective induction of tumor cell apoptosis without toxicity to
      normal tissues. Here we report that TRAIL failed to induce apoptosis in SCLC
      cells and instead resulted in an up to 40% increase in proliferation. TRAIL
      induced SCLC cell proliferation was mediated by extracellular signal-regulated
      kinase 1 and 2, and dependent on the expression of surface TRAIL-receptor 2
      (TRAIL-R2) and lack of caspase-8, which is frequent in SCLC. Treatment of SCLC
      cells with interferon-gamma (IFN-gamma) restored caspase-8 expression and
      facilitated TRAIL-induced apoptosis. The overall loss of cell
      proliferation/viability upon treatment with the IFN-gamma-TRAIL combination was
      70% compared to TRAIL-only treated cells and more than 30% compared to untreated
      cells. Similar results were obtained by transfection of cells with a caspase-8
      gene construct. Altogether, our data suggest that TRAIL-R2 expression in the
      absence of caspase-8 is a negative determinant for the outcome of TRAIL-based
      cancer therapy, and provides the rationale for using IFN-gamma or other
      strategies able to restore caspase-8 expression to convert TRAIL from a pro
      survival into a death ligand.

PMID- 18093696
TI  - Seizures in the developing brain: cellular and molecular mechanisms of neuronal
      damage, neurogenesis and cellular reorganization.
AB  - Epilepsy is a common neurological disorder that occurs more frequently in
      children than in adults. The extent that prolonged seizure activity, i.e. status
      epilepticus (SE), and repeated, brief seizures affect neuronal structure and
      function in both the immature and mature brain has been the subject of increasing
      clinical and experimental research. Earlier studies suggest that seizure-induced
      effects in the immature brain compared with the adult brain are different. This
      is manifested as differences in neuronal vulnerability, cellular and synaptic
      reorganization and regenerative processes. The focus of this review is first to
      give a short overview of currently used experimental models of epilepsy in
      immature rats, and then discuss more thoroughly seizure-induced acute and sub
      acute cellular and molecular alterations, highlight the contribution of
      inflammatory-like reactions and intracellular cytoskeleton to the insult, and
      reveal changes in the structure and function of inhibitory GABA(A) and excitatory
      glutamate receptors. The role of seizure-activated reparative, plastic processes,
      synaptic remodelling, neurogenesis as well as the long-term consequences of
      seizures are briefly outlined. The main emphasis is put on studies carried out in
      experimental animals, and the focus of interest is the hippocampus, the brain
      area of great vulnerability in epilepsy. In vitro studies are discussed only to
      limited extent. Collectively, recent studies suggest that the deleterious effects
      of seizures may not solely be a consequence of neuronal damage and loss per se,
      but could be due to the fact that seizures interfere with the highly regulated
      developmental processes in the immature brain.

PMID- 18093695
TI  - The dopaminergic neurotransmitter system is associated with aggression and
      agitation in frontotemporal dementia.
AB  - To identify neurochemical correlates of behavioral and psychological signs and
      symptoms of dementia (BPSD), we set up a prospective study. Patients with
      probable Alzheimer's disease (AD) (n=181), mixed dementia (MXD) (n=28),
      frontotemporal dementia (FTD) (n=25) and dementia with Lewy bodies (DLB) (n=24)
      were included. At inclusion, all patients underwent lumbar puncture,
      neuropsychological examination and behavioral assessment (battery of behavioral
      assessment scales). Cerebrospinal fluid (CSF) levels of norepinephrine and of
      (nor)epinephrine (MHPG), serotonin (5HIAA) and dopamine (DOPAC, HVA) metabolites
      were determined by HPLC and electrochemical detection. Spearman Rank-Order
      followed by Bonferroni correction was used for calculating correlations. In FTD
      patients, CSF norepinephrine levels were positively correlated with dementia
      severity (r=0.539; p=0.021). CSF DOPAC levels were correlated with BPSD in
      general (r=0.537; p=0.007), associated caregiver burden (r=0.567; p=0.004) and
      agitated and aggressive behavior (r=0.568; p=0.004). In a subgroup of FTD
      patients who did not receive psychotropic pharmacological treatment, a strong
      correlation between CSF HVA/5HIAA ratios (reflecting serotonergic modulation of
      dopaminergic neurotransmission) and aggressive behavior (r=0.758; p=0.009) was
      found. In MXD patients, (verbally) agitated behavior was positively associated
      with the turnover of norepinephrine (r=0.633; p=0.002). No significant
      correlations were found in AD and DLB groups. In FTD, increased activity of
      dopaminergic neurotransmission and altered serotonergic modulation of
      dopaminergic neurotransmission is associated with agitated and aggressive
      behavior respectively. This study demonstrated that neurochemical mechanisms
      underlying the pathophysiology of BPSD are both BPSD-specific and disease
      specific which might have implications for future development of new and more
      selective pharmacological treatments of BPSD.

PMID- 18093697
TI  - Effects of 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid and its
      ester derivatives on biofilm formation by two oral pathogens, Porphyromonas
      gingivalis and Streptococcus mutans.
AB  - The aim of this study was to investigate the effect of 3-(4'-geranyloxy-3'
      methoxyphenyl)-2-trans propenoic acid, active principle isolated from Acronychia
      baueri Schott, and its ester derivatives on biofilm formation by two important
      oral pathogens, Porphyromonas gingivalis and Streptococcus mutans. The parent
      acid and conjugates with vanillic acid, 2-hydroxynaphthoquinone and guaiacol
      caused a significant and reproducible inhibition of P. gingivalis biofilm
      formation. This effect could be related to the ability of the compounds to
      inhibit bacterial growth. These compounds also efficiently caused a reduction of
      biofilm formation by S. mutans, a phenomenon not related to growth inhibition.
      These data suggest that 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid
      and some of its ester derivatives may have a therapeutic/preventive potential for
      oral infections.

PMID- 18093698
TI  - A combination in-ovo vaccine for avian influenza virus and Newcastle disease
      virus.
AB  - The protection of poultry from H5N1 highly pathogenic avian influenza A (HPAI)
      and Newcastle disease virus (NDV) can be achieved through vaccination, as part of
      a broader disease control strategy. We have previously generated a recombinant
      influenza virus expressing, (i) an H5 hemagglutinin protein, modified by the
      removal of the polybasic cleavage peptide and (ii) the ectodomain of the NDV
      hemagglutinin-neuraminidase (HN) protein in the place of the ectodomain of
      influenza neuraminidase (Park MS, et al. Proc Natl Acad Sci USA 2006;103(21):8203
      8). Here we show this virus is attenuated in primary normal human bronchial
      epithelial (NHBE) cell culture, and demonstrate protection of C57BL/6 mice from
      lethal challenge with an H5 HA-containing influenza virus through immunisation
      with the recombinant virus. In addition, in-ovo vaccination of 18-day-old
      embryonated chicken eggs provided 90% and 80% protection against highly stringent
      lethal challenge by NDV and H5N1 virus, respectively. We propose that this virus
      has potential as a safe in-ovo live, attenuated, bivalent avian influenza and
      Newcastle disease virus vaccine.

PMID- 18093699
TI  - Abortive reaction and time of scar formation after BCG vaccination.
AB  - We describe two practical issues regarding BCG vaccination that merit attention.
      These are time of scar formation after BCG vaccination and abortive reaction.
      Scar formation after vaccination may take 6 months or more. Babies showing
      abortive reaction after BCG reaction should be considered different from non
      reactors. All health care providers and vaccinologists should be sensitized that
      abortive reaction is one of the local reactions after BCG vaccination.

PMID- 18093700
TI  - European citizens' opinions on immunisation.
AB  - As part of a larger study exploring how European citizens' balance issues of
      public and private interest and the extent to which they are prepared to accept
      State intervention on a range of public health issues, focus group participants
      were asked whether childhood immunisation should be a matter of parental choice
      or State compulsion. The question was debated in 66 (of 96) focus groups held
      across 16 European countries in 2003. Discussions focused on the concept of risk,
      trust in health professionals and the State, upholding the status quo, fears over
      vaccine safety and perceptions of infectious disease as a 'foreign threat'.

PMID- 18093701
TI  - Inactivated influenza vaccine (IIV) in children <2 years of age: examination of
      selected adverse events reported to the Vaccine Adverse Event Reporting System
      (VAERS) after thimerosal-free or thimerosal-containing vaccine.
AB  - Thimerosal as a preservative (in all but trace amounts) was removed from vaccines
      used in infants starting in the late 1990s, though the preservative-including
      inactivated influenza vaccine is still available for use in individuals >or=6
      months of age. We compared the proportion of injection site reactions, rash, and
      infections reported to the Vaccine Adverse Event Reporting System (VAERS) after
      preservative-free (PFV), preservative-including (PIV), and preservative unknown
      (PUV) vaccines in reports from 7/1/2004 to 1/4/2006. There were 145, 175, and 216
      reports after vaccination with PFV, PIV, and PUV, respectively. The most
      frequently reported coding terms (fever, rash, and urticaria) were seen in
      similar proportions in the PFV, PIV, and PUV groups. No difference was detected
      in the proportion of injection site reactions (ISR), rash, or infections in the
      PIV, PFV, and PUV reports. Keeping in mind the inherent limitations of VAERS,
      including underreporting and potential reporting biases, we conclude that there
      were no substantial differences in the proportion of rash, ISR, and infection
      reports in the PIV, PFV and PUV reports in infants.

PMID- 18093702
TI  - Low prevalence of recently discovered pneumococcal serotype 6C isolates among
      healthy Dutch children in the pre-vaccination era.

PMID- 18093703
TI  - Improved protection against simian immunodeficiency virus mucosal challenge in
      macaques primed with a DNA vaccine and boosted with the recombinant modified
      vaccinia virus Ankara and recombinant Semliki Forest virus.
AB  - Using the experimental infection of cynomolgus macaques with simian
      immunodeficiency virus (SIV) as a model of human immunodeficiency virus infection
      in humans, we studied the immunogenicity and protective efficacy of a vaccine
      strategy combining DNA, the modified recombinant vaccinia virus strain Ankara
      (MVA) and Semliki Forest virus (SFV) expressing gag, pol, env, tat, rev and nef
      from SIV. Although this immunization strategy induced moderate immune responses,
      the control of pathogenic SIVmac251 infection following mucosal challenge was
      clearly improved by vaccination. The viral load in vaccinated animals was reduced
      by 2 logs during the acute phase of infection and, in five of the six macaques,
      viral load fell below the detection limit at set point. No correlates of immune
      protection were identified, but SIV-specific T-cell responses were detected
      earlier in vaccinated animals than in controls. These results highlight the power
      of live attenuated virus vectors for vaccination strategies.

PMID- 18093704
TI  - Protection of mice from Shiga toxin-2 toxemia by mucosal vaccine of Shiga toxin
      2B-His with Escherichia coli enterotoxin.
AB  - Escherichia coli O157:H7 produces Stx1 and Stx2 causing severe diseases. Their B
      subunits (StxBs) are useful for a vaccine but exhibit low immunogenicity,
      especially Stx2B. Nasal vaccination with StxBs plus cholera toxin induces only
      serum anti-Stx1B antibodies in mice. However, nasal administration of a mutant of
      E. coli enterotoxin and His-tagged Stx2B induced serum antibodies neutralizing
      Stx2 in vitro or in vivo and mucosal IgA antibodies in lungs. As His-tagged Stx2B
      showed five or three polymers in gel filtration chromatography, His-tagged Stx2B
      forms smaller tertiary structure than the native one and is effective for
      preventing Stx2 toxemia as a nasal vaccine.

PMID- 18093705
TI  - Heterologous prime-boost vaccination with a non-replicative vaccinia recombinant
      vector expressing LACK confers protection against canine visceral leishmaniasis
      with a predominant Th1-specific immune response.
AB  - Leishmaniasis caused by Leishmania infantum is a severe endemic disease in the
      Mediterranean basin, being domestic dogs the main reservoir of the disease that
      plays a key role in the transmission to humans. Studies on vaccines against
      canine leishmaniasis, aimed to modify the T cell repertoire, have advanced in
      recent years. LACK vaccination assays, using protein or DNA vectors, show
      protection against cutaneous L. major infections by redirecting the early IL-4
      responses to a protective Th1 response. The aim of this study was to define the
      effectiveness and type of immune response in a canine visceral leishmaniasis
      model of two poxvirus vectors (Western reserve strain, WR and modified vaccinia
      virus Ankara, MVA) expressing the LACK protein of L. infantum in prime/boost
      vaccination protocols. The results obtained showed that dog vaccination priming
      with DNA-LACK followed by a booster with MVA-LACK or rVV-LACK triggered a Th1
      type of immune response, leading to protection against canine visceral
      leishmaniasis. This protection correlated with absence of visceral leishmaniasis
      symptoms, lower Leishmania-specific antibodies, higher degree of T cell
      activation in Leishmania-target organs and higher synthesis of Th1 cytokines. In
      addition, we found that dogs boosted with the non-replicative virus show less VL
      symptoms and higher degree of T cell activation, providing evidences for a clear
      advantage of MVA-LACK as a vaccination vector against canine visceral
      leishmaniasis.

PMID- 18093706
TI  - The effect of oral administration of a homologous hilA mutant strain on the long
      term colonization and transmission of Salmonella Enteritidis in broiler chickens.
AB  - The effect of pre-treatment with a homologous live Salmonella hilA mutant strain
      on the long-term colonization and transmission of Salmonella Enteritidis in
      broilers was evaluated. For this purpose, three treatment groups of newly hatched
      broilers were created. Each group consisted of 4 pens with 25 birds per pen. The
      first and second groups were orally inoculated with a Salmonella Enteritidis hilA
      mutant strain (Nal r) whereas the third group was not. In the second and third
      group, 20% of the birds were challenged 1 day later with a Salmonella Enteritidis
      wild type strain (Strep r). The Salmonella Enteritidis hilA mutant strain showed
      no residual virulence in the chicken host and was largely cleared from the
      chickens at 6 weeks of age. A significant long-term inhibition of faecal shedding
      and caecal and internal organ colonization of the wild type Salmonella
      Enteritidis strain was observed in the birds pre-treated with the hilA mutant
      strain. Although pre-treatment with a hilA mutant strain could not fully prevent
      the spread of Salmonella Enteritidis amongst the broilers, a significant
      reduction of transmission was observed in comparison to the non-pre-treated
      groups. The observed colonization-inhibition (CI) indicates that administration
      of live attenuated hilA mutant Salmonella strains to newly hatched chicks might,
      in combination with other protective control measures, contribute to the control
      of Salmonella infections in broilers.

PMID- 18093707
TI  - Expression of Glut-1 in primary and recurrent head and neck squamous cell
      carcinomas, and compared with 2-[18F]fluoro-2-deoxy-D-glucose accumulation in
      positron emission tomography.
AB  - The aim of the study was to investigate the pattern of glucose transporter-1
      (Glut-1) expression in primary and recurrent head and neck squamous cell
      carcinomas (HNSCCAs) and the relation between Glut-1 expression and 2-[18F]fluoro
      2-deoxy-D-glucose - positron emission tomography (FDG-PET). Standardised uptake
      values (SUVs) were used to evaluate FDG uptake by the tumour. Sections were
      stained immunohistochemically for Glut-1, which showed that high SUVs were seen
      in all HNSCCAs, and patients with higher T stage tumours or less well
      differentiated tumours showed significantly higher SUVs than those with lower
      stage tumours or better-differentiated tumours (P=0.001 and 0.04, respectively).
      Glut-1 immunostaining was present in all cases. The Glut-1 staining index in
      primary HNSCCAs was significantly lower than that in recurrent HNSCCAs (P=0.03),
      and the index of better-differentiated tumours lower than that of poorly
      differentiated tumours (P=0.02). However, there was no significant correlation
      between SUV(mean) and the Glut-1 staining index. In conclusion, our data suggest
      that high FDG uptakes were seen with overexpression of Glut-1 in primary and
      recurrent HNSCCAs. SUV(mean) was related to tumour T stage and grade of
      differentiation, which indicated that SUV was helpful in evaluating tumours. The
      expression of Glut-1 in recurrent HNSCCAs was higher than that in primary
      HNSCCAs, and in poorly-differentiated HNSCCAs higher than in better
      differentiated HNSCCAs, which indicated that Glut-1 may have a useful role as a
      predictor for poor prognosis in HNSCCAs. However, there was no significant
      correlation between FDG accumulation and Glut-1 expression.

PMID- 18093708
TI  - Effects of seated whole-body vibration on postural control of the trunk during
      unstable seated balance.
AB  - BACKGROUND: Low back disorders and their prevention is of great importance for
      companies and their employees. Whole-body vibration is thought to be a risk
      factor for low back disorders, but the neuromuscular, biomechanical, and/or
      physiological mechanisms responsible for this increased risk are unclear. The
      purpose of this study was to measure the acute effect of seated whole-body
      vibration on the postural control of the trunk during unstable seated balance.
      METHODS: Twenty-one healthy subjects (age: 23 years (SD 4 years)) were tested on
      a wobble chair designed to measure trunk postural control. Measurements of
      kinematic variance and non-linear stability control were based on seat angle
      before and after 30 min of seated whole-body vibration (bandwidth=2-20 Hz, root
      mean-squared amplitude=1.15m/s(2)). FINDINGS: All measures of kinematic variance
      of unstable seated balance increased (P<0.05) after vibration including: ellipse
      area (35.5%), root-mean-squared radial lean angle (17.9%), and path length
      (12.2%). Measures of non-linear stability control also increased (P<0.05)
      including Lyapunov exponent (8.78%), stability diffusion analysis (1.95%), and
      Hurst rescaled range analysis (5.2%). INTERPRETATION: Whole-body vibration
      impaired postural control of the trunk as evidenced by the increase in kinematic
      variance and non-linear stability control measures during unstable sitting. These
      findings imply an impairment in spinal stability and a mechanism by which
      vibration may increase low back injury risk. Future work should investigate the
      effects of whole-body vibration on the anatomical and neuromuscular components
      that contribute to spinal stability.

PMID- 18093709
TI  - The effect of on-body lift assistive device on the lumbar 3D dynamic moments and
      EMG during asymmetric freestyle lifting.
AB  - BACKGROUND: A new on-body personal lift assistive device was developed to reduce
      force requirements of back muscles during lifting and static holding tasks.
      METHODS: Nine male subjects participated in the study. Twelve Fastrak sensors
      were used to record positions and rotations of the segments. Trunk muscles were
      normalized to maximum and integrated electromyographic amplitudes of the left and
      right thoracic erector spinae, lumbar erector spinae, external obliques, and
      rectus abdominalis were compared in asymmetrical lifting for three different
      loads (5 kg, 15 kg, 25 kg) using free style under two conditions: with and
      without a lift assistive device. FINDINGS: The assistive device significantly
      reduced the required muscular effort of the lumbar and thoracic erector spinae
      (P=0.001) with no significant differences in the level of abdominal muscular
      activity. Average integrated electromyography amplitudes were reduced across all
      subjects by 23.9% for lumbar erector spinae, 24.4% for thoracic erector spinae,
      and 34.9% for the contralateral external oblique muscles. The assistive device
      had its greatest impact on smaller moments with 30% reduction in lateral bending,
      and 24% reduction in rotational moments, with only 19.5% a reduction in larger
      flexion-extension moments. To investigate whether the lift assistive device
      affected lifting kinematics, the device tensions were zeroed mathematically. No
      kinematic differences in lifting technique would explain this magnitude of moment
      reduction. INTERPRETATION: The on-body assistive device reduced the required
      muscular effort of the lumbar and thoracic erector spinae without adversely
      affecting the level of abdominal muscle activity. These reductions were mirrored
      by similar 3D moment reductions.

PMID- 18093710
TI  - Comparison of benthic macroinvertebrate indices for the assessment of the impact
      of acid mine drainage on an Irish river below an abandoned Cu-S mine.
AB  - A range of macroinvertebrate indices were compared to assess the most appropriate
      metric for the assessment of acid mine drainage (AMD) in a low alkalinity, highly
      erosional river in south-east Ireland. Differences were found in the ability of
      indices to discriminate AMD impact with the Brillouin, BMWP score, Margalef and
      Shannon Indices the most precise. Taxon richness was also strongly correlated
      with AMD indicator parameters (e.g. pH alkalinity, sulphate, Zn and Fe) at
      impacted sites being an equally reliable metric. The response of the community
      structure to AMD in this river does not fulfil the optimum criteria for either
      diversity or biological indices, which may explain the variation in the success
      of different indices seen in this and other studies. The development of indices
      that model the expected community response to AMD more accurately or are based on
      the response of indicator species to AMD pollutants are required.

PMID- 18093711
TI  - Release of polycyclic aromatic hydrocarbons from Yangtze River sediment cores
      during periods of simulated resuspension.
AB  - The role of resuspension duration on release of 16 PAHs was measured
      experimentally using a particle entrainment simulator (PES). Three sediment cores
      were resuspended for 12h at 0.2 and 0.5 N m(-2). PAHs in water column and total
      suspended solids (TSS) were monitored at intervals. After 0.25 h of resuspension,
      PAH release was on average 42% of their concentrations after 12h of resuspension,
      indicating fast release of PAHs from sediments in an initial short time.
      Moreover, PAHs released faster at 0.5 N m(-2) than at 0.2N m(-2); low molecular
      weight PAHs (2-3-ring) released faster than median molecular weight (4-ring)
      PAHs. PAH concentrations in TSS showed generally increase with time and
      differences in magnitudes based on sediment type and energy. Overall, the
      composition of sediments is the major factor in determining the amount of
      released PAHs, more so than the level of resuspension energy applied.

PMID- 18093712
TI  - Antidepressant-like effects of the mixture of honokiol and magnolol from the
      barks of Magnolia officinalis in stressed rodents.
AB  - Honokiol and magnolol are the main constituents simultaneously identified in the
      barks of Magnolia officinalis, which have been used in traditional Chinese
      medicine to treat a variety of mental disorders including depression. In the
      present study, we reported on the antidepressant-like effects of oral
      administration of the mixture of honokiol and magnolol in well-validated models
      of depression in rodents: forced swimming test (FST), tail suspension test (TST)
      and chronic mild stress (CMS) model. The mixture of honokiol and magnolol
      significantly decreased immobility time in the mouse FST and TST, and reversed
      CMS-induced reduction in sucrose consumption to prevent anhedonia in rats.
      However, this mixture was unable to affect ambulatory or rearing behavior in the
      mouse open-field test. CMS induced alterations in 5-hydroxytryptamine (5-HT) and
      its metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels in various brain
      regions of rats. An increase in serum corticosterone concentrations and a
      reduction in platelet adenylyl cyclase (AC) activity were simultaneously found in
      the CMS rats. The mixture of honokiol and magnolol at 20 and 40 mg/kg
      significantly attenuated CMS-induced decreases of 5-HT levels in frontal cortex,
      hippocampus, striatum, hypothalamus and nucleus accumbens. And it markedly
      increased 5-HIAA levels in frontal cortex, striatum and nucleus accumbens at 40
      mg/kg and in frontal cortex at 20 mg/kg in the CMS rats. A subsequent reduction
      in 5-HIAA/5-HT ratio was found in hippocampus and nucleus accumbens in the CMS
      rats receiving this mixture. Furthermore, the mixture of honokiol and magnolol
      reduced elevated corticosterone concentrations in serum to normalize the
      hypothalamic-pituitary-adrenal (HPA) hyperactivity in the CMS rats. It also
      reversed CMS-induced reduction in platelet AC activity, via upregulating the
      cyclic adenosine monophosphate (cAMP) pathway. These results suggested that the
      mixture of honokiol and magnolol possessed potent antidepressant-like properties
      in behaviors involved in normalization of biochemical abnormalities in brain 5-HT
      and 5-HIAA, serum corticosterone levels and platelet AC activity in the CMS rats.
      Our findings could provide a basis for examining directly the interaction of the
      serotonergic system, the HPA axis and AC-cAMP pathway underlying the link between
      depression and treatment with the mixture of honokiol and magnolol.

PMID- 18093713
TI  - Heavy drinking as a differential predictor of physical aggression in clinical and
      general populations.
AB  - OBJECTIVE: Whereas the association between heavy alcohol use and physical
      aggression (PA) is documented in alcohol dependent patients and the general
      population, comparison studies between populations treated for alcohol dependence
      and general population are lacking. In this study the nature of association
      between heavy drinking and PA was explored both in alcohol dependent inpatients
      and the general population. METHOD: Three hundred thirty inpatients with alcohol
      dependence and 1199 adult subjects representing the general population were
      examined with PA score of Buss-Perry Aggression Questionnaire and the AUDIT
      scores. Relationship between PA and AUDIT total score was investigated with
      ANCOVA analysis. RESULTS: Significant association was found between alcohol use
      and PA in the ANCOVA analyses in both the inpatient and the control (general
      population) samples. At lower severity of alcohol use (total AUDIT score<8) the
      clinical sample showed a substantially higher severity of PA than the control
      sample, but at higher severity of alcohol use the control sample displayed a
      higher score of PA compared to the clinical sample. CONCLUSIONS: Clinical and
      general populations may need different risk management strategies in order to
      address their needs in rationalistic way.

PMID- 18093714
TI  - Effects of nonylphenol on the calcium signal and catecholamine secretion coupled
      with nicotinic acetylcholine receptors in bovine adrenal chromaffin cells.
AB  - Nonylphenol (NP) is the most critical metabolite of alkylphenol polyethoxylate
      detergents. NP is known as an endocrine disruptor with estrogenic activities and
      as an inhibitor of endoplasmic reticulum Ca(2+)-ATPase. Estrogen has modulatory
      roles on ligand-gated ion channels, such as nicotinic acetylcholine receptors
      (nAChRs). Ca(2+)-ATPase inhibitors can modulate the cytosolic calcium
      concentration ([Ca(2+)](c)]) and thus can affect the calcium signaling coupled
      with nAChRs. Therefore, NP is predicted to have complex effects on the Ca(2+)
      signaling and secretion coupled with nAChRs. This study investigated these
      effects using bovine adrenal chromaffin cells. The results show that NP
      suppressed the Ca(2+) signaling coupled with nAChRs and voltage-operated Ca(2+)
      channels in a dose-dependent manner, with IC(50)s of 1 and 5.9 microM,
      respectively. Estradiol exhibits similar suppression but much lower inhibitory
      potencies. NP alone induced a transient rise in [Ca(2+)](c) in the presence or
      absence of extracellular calcium. Thapsigargin, an endoplasmic reticulum Ca(2+)
      ATPase inhibitor, partially suppressed the [Ca(2+)](c) rise induced by NP, but NP
      totally blocked the [Ca(2+)](c) rise induced by thapsigargin. This illustrates
      that NP can cause Ca(2+) release from thapsigargin-insensitive pools.
      Thapsigargin suppressed the Ca(2+) signaling coupled with nAChRs but increased
      that coupled with voltage-operated Ca(2+) channels. We propose that three routes
      are responsible for the effects of NP on nAChRs: named receptor channels, voltage
      gated Ca(2+) channels, and Ca(2+)-induced Ca(2+) release. Three routes are
      related to the characteristics of NP as steroid-like compounds and Ca(2+)-ATPase
      inhibitor.

PMID- 18093715
TI  - Bonding of brackets using a caries-protective adhesive patch.
AB  - OBJECTIVES: The purpose of this study was to assess the shear bond strength (SBS)
      of metal brackets when placed with a caries protective adhesive patch. METHODS:
      Forty stainless steel brackets (Ormco) were bonded to 40 bovine enamel samples
      according to the following conditioning/bonding procedures using a resin-based
      orthodontic luting material (Heliosit Orthodontic, N=10 per group): (A) 35%
      phosphoric acid (30s), rinse and dry; (B) as in A but additional placement of a
      prototype adhesive patch (Ivoclar Vivadent) using a bonding agent (Heliobond);
      (C) application of a two-step self-etch adhesive (AdheSE); (D) as in C but
      additional patch placement. Samples were stored at 37 degrees C for 24h. SBS was
      measured with a universal testing machine with a crosshead speed of 0.5mm/min and
      the adhesive remnant index (ARI) was determined under a stereomicroscope (16x).
      RESULTS: Mean SBS (standard deviation) values were as follows: (A) 16.6 (6.4)MPa;
      (B) 12.2 (5.8); (C) 12.9 (5.0); and (D) 10.5 (4.7). Analysis of variance followed
      by Bonferroni correction revealed no statistically significant differences. In 2
      (B) and 4 (D) specimens, complete retention of the adhesive patch was observed.
      CONCLUSIONS: All treatment groups showed adequate bond strength values. The
      adhesive patch could therefore be applied in combination with orthodontic
      brackets and seal the enamel adjacent to the bracket.

PMID- 18093716
TI  - Timing of caffeine's impact on autonomic and central nervous system measures:
      clarification of arousal effects.
AB  - The timing of caffeine effects on arousal levels was examined. From previous work
      in our laboratory, an increase in skin conductance level (SCL) was used as the
      marker of arousal increase, and we sought to identify the timing of this and
      related effects following caffeine ingestion. A single oral dose of caffeine (250
      mg) was used in a randomised double-blind placebo-controlled repeated-measures
      cross-over study. Eyes-closed resting electroencephalogram (EEG) and autonomic
      data (SCL, heart rate, respiration rate, and systolic and diastolic blood
      pressure) during 2 min epochs that commenced every 4 min after ingestion, were
      analysed. The SCL placebo data were used to identify potential arousal measures
      prior to examining caffeine effects. Caffeine was associated with increased SCL,
      increased respiratory rate and a global reduction in alpha power. There were no
      significant cardiovascular effects of caffeine-induced arousal. These caffeine
      results are consistent with our recent electrodermal and EEG studies of arousal,
      and confirm the potential use of caffeine as a simple means of experimentally
      modifying arousal levels without task-related confounds.

PMID- 18093718
TI  - Covert respiration measures for the detection of concealed information.
AB  - A mock-theft experiment was designed to assess the efficiency of two covert
      respiration measures in detection of concealed information. The covert measures
      were further compared with three standard measures typically used for the
      detection of concealed knowledge (electrodermal, respiration and finger pulse
      measures). Results revealed that the covert respiration measures produced good
      discrimination between "guilty" (participants possessing concealed knowledge) and
      "innocent" participants. One of the covert measures produced detection efficiency
      that was similar to that of the standard respiration and finger pulse measures,
      but less than the electrodermal measure.

PMID- 18093717
TI  - Workload assessment of computer gaming using a single-stimulus event-related
      potential paradigm.
AB  - Behavioral and event-related potential (ERP) measures were used to assess
      cognitive workload from expert computer gamers playing a "first-person shooter"
      video game. Game difficulty level was manipulated in separate conditions by
      adjusting the number of enemies (view, easy, medium, and hard). Infrequently
      presented single-stimulus tones were either ignored or counted across difficulty
      conditions. Game performance and tone-counting accuracy declined as game
      difficulty increased. ERP component amplitudes diminished for both the tone
      ignore and counting conditions as game difficulty increased. The findings suggest
      that cognitive workload induced by video gaming can be reliably assessed through
      behavioral and neuroelectric means, and that the single-stimulus paradigm can be
      a useful tool for evaluating workload in an immersive stimulus environment with
      less distraction than conventional tools.

PMID- 18093719
TI  - A study to establish gestation-specific reference intervals for thyroid function
      tests in normal singleton pregnancy.
AB  - OBJECTIVE: To establish gestation-specific reference intervals for thyroid
      function tests in normal singleton pregnancy. STUDY DESIGN: Cross-sectional
      observational study performed in the Obstetric and Gynaecology department, West
      Middlesex University Hospital. A single blood sample from 335 pregnant women at
      various gestations of pregnancy was analysed for thyroid function. FT4, fT3, TSH
      values at each gestation of pregnancy were calculated. RESULTS: From the fT3, fT4
      and TSH results, a 95% reference interval was calculated for each hormone for
      each week of pregnancy. CONCLUSION: We calculated gestation-specific reference
      intervals for thyroid function tests throughout pregnancy to facilitate clinical
      management of thyroid disease in pregnancy.

PMID- 18093720
TI  - Differences in screening history, tumour characteristics and survival between
      women with screen-detected versus not screen-detected cervical cancer in the east
      of The Netherlands, 1992-2001.
AB  - OBJECTIVE: In The Netherlands, despite a national screening programme since 1996,
      invasive cervical cancers have been detected in screened and non-screened women.
      The aim of this study was to determine differences between Pap-smear history,
      tumour characteristics and survival of patients with a tumour detected by the
      screening programme (SP) or outside the screening programme (OSP) in the region
      of the Comprehensive Cancer Centre Stedendriehoek Twente in the period 1992-2001.
      STUDY DESIGN: In this period, 263 cervical cancer cases in women aged 30-60 were
      selected from the regional cancer registry. Patient and tumour characteristics,
      treatment and follow-up data were extracted. Also, detection modality of the
      tumour and Pap score of the smear which led to the diagnosis ('diagnostic smear')
      and the 'previous smear' were registered. RESULTS: Thirty-five percent were SP
      tumours and 65% were OSP tumours. SP tumours had a lower stage (FIGO I) than OSP
      tumours: 84% versus 57%. The OSP group exhibited a twofold increase in risk of
      death (p<0.05) compared to the SP group. Subsequently 61 women (23%) and 46 (17%)
      women had an abnormal Pap smear (Pap II or higher) 5 and 3 years before the
      'diagnostic smear', respectively. Furthermore, 37 women (14%) and 23 women (9%)
      had a normal smear 5 and 3 years before diagnosis, respectively. CONCLUSION: SP
      tumours have a lower stage and a better prognosis, probably due to the fact that
      the screening programme detects the slow growing tumours which in general have a
      better prognosis. Furthermore, detection and treatment of patients with
      suspicious smears have been suboptimal and attention should therefore be paid to
      prompt follow-up of suspicious smears.

PMID- 18093721
TI  - Painful hydronephrosis of pregnancy.

PMID- 18093722
TI  - The search for better prognostic factors for men treated for localized prostate
      cancer continues.

PMID- 18093723
TI  - Nomograms are difficult to beat.

PMID- 18093724
TI  - Re: Wayne J.G. Hellstrom, Marc Gittelman, Jonathan Jarow, et al. an evaluation of
      semen characteristics in men 45 years of age or older after daily dosing with
      tadalafil 20 mg: results of a multicenter, randomized, double-blind, placebo
      controlled, 9-month study. Eur Urol 2008;53:1058-65.

PMID- 18093725
TI  - Clinical, magnetic resonance imaging, cerebrospinal fluid and
      electrophysiological characteristics of the earliest multiple sclerosis.
AB  - OBJECTIVES: The vast majority of clinically isolated syndrome (CIS) patients with
      at least two silent brain MRI lesions progress to multiple sclerosis (MS) as
      early as after 2 years meaning that they actually have MS, the earliest MS.
      Effective therapy with interferon beta preparations in patients with the earliest
      MS demands early and accurate diagnosis of the disease. PATIENTS AND METHODS: In
      order to find the differentiating clinical and paraclinical characteristics of
      patients with the earliest MS we compared clinical, MRI, CSF and evoked potential
      findings in patients with the earliest MS and patients with relapsing-remitting
      (RR) MS. Retrospective analysis included 149 patients (103 women), among them 40
      patients with the earliest MS and 95 patients with RR MS. RESULTS: Patients with
      the earliest MS had more often predominant afferent symptoms (p=0.023) but less
      often predominant cerebellar (p=0.033) and efferent symptoms (p=0.012) than
      patients with RR MS. They were less likely to fulfill the Barkhof brain MRI
      criteria (p=0.050) and had less often prolonged latencies of visual evoked
      potentials (VEP) (p=0.006) than patients with RR MS. On the other hand they were
      more likely to have elevated CSF cells (p=0.010) than patients with RR MS and had
      as often present CSF oligoclonal bands (p=0.112). CONCLUSION: The differentiating
      characteristics of patients with the earliest MS are predominance of afferent
      symptoms, less brain MRI dissemination and more frequently normal VEP, but on the
      other hand abnormal CSF findings with elevated CSF cells and positive oligoclonal
      bands.

PMID- 18093726
TI  - Increased levels of elastin-derived peptides in cerebrospinal fluid of patients
      with lacunar stroke.
AB  - OBJECTIVE: To investigate whether elastin-derived peptides (EDP) are detectable
      in the cerebrospinal fluid (CSF) of healthy controls and of patients with acute
      brain ischemia and if so to assess possible trends in EDP levels in different
      groups of ischemic stroke patients (small-vessel disease vs. other ischemic
      strokes; first-ever vs. recurrent stroke). PATIENTS AND METHODS: Levels of EDP
      were determined by ELISA in blood sera and CSF of 80 patients with acute ischemic
      stroke (mean age 61.5+/-10.8; age range 47-70; 22 women) and in 15 healthy age-
      and sex-matched controls (mean age 57.3+/-13.4; age range 50-65). The patients
      were divided into a group with first ever lacunar stroke (27); first ever non
      lacunar ischemic stroke (27) and recurrent stroke (26). EDP were measured early
      (mean 7 days, range 1-15) after stroke onset. RESULTS: Serum EDP levels were
      mildly higher in recurrent strokes as compared to first ever lacunar lesion and
      controls. However, in the CSF the concentrations of EDP in stroke patients were
      strongly elevated (from 2 up to 30 times depending on subgroup) as compared with
      healthy subjects. The highest level of EDP in CSF and in the serum was found in
      recurrent strokes. Subgroup analysis revealed a trend for significantly higher
      EDP concentrations in CSF in lacunar and recurrent stroke as compared with non
      lacunar. CONCLUSIONS: This study is the first application of elastin peptide
      measurement to human CSF and stroke patients. The increased levels of EDP were
      detected in CSF of patients with lacunar and recurrent strokes.

PMID- 18093727
TI  - Platycodin D induces apoptosis and decreases telomerase activity in human
      leukemia cells.
AB  - Platycodin D (PD) is a major constituent of triterpene saponins found in the root
      of Platycodon grandiflorum. Recent studies have demonstrated that PD is a
      potentially interesting candidate for use in cancer chemotherapy. However, the
      molecular mechanisms responsible for PD-induced telomerase inhibition remain to
      be poorly known. In this study, we examined the effects of PD treatment on
      telomerase activity in different human leukemia cell lines. At concentrations
      between 10 and 20 microM, PD exerted a dose-dependent direct cytotoxic effect and
      inhibition of telomerase activity via downregulation of hTERT expression. Because
      c-Myc and Sp1 are known to directly regulate transcription of hTERT, we also
      evaluated the expression and DNA binding activity of these proteins. PD treatment
      reduced c-Myc and Sp1 protein levels and DNA binding activities in a dose
      dependent manner. We also observed that PD treatment downregulates the activation
      of Akt, thereby reducing the phosphorylation and nuclear translocation of hTERT.
      We conclude that PD has direct cytotoxic effect on human leukemia cells and
      suppresses telomerase activity through transcriptional and posttranslational
      suppression of hTERT.

PMID- 18093728
TI  - Removal of mercury(II) from wastewater using camel bone charcoal.
AB  - Camel bone charcoal is used as an adsorbent for the removal of Hg(II) from
      wastewater effluents. The equilibrium data are fitted to Langmiur isotherm rather
      than linear and Freundlich isotherms. The adsorption capacity Qo is 28.24 mg of
      Hg(II)/g of the adsorbent. The optimum removal conditions are pH 2, contact time
      30 min and temperature 25 degrees C. A comparison of the adsorption capacity (Qo)
      of camel bone charcoal with different adsorbents previously used for Hg(II)
      removal from wastewater effluents reveals its remarkable efficiency over many
      other treated and untreated natural and synthetic adsorbents. X-ray fluorescence
      and infrared spectrometry of camel bone charcoal after contact with mercury
      solutions confirm surface adsorption of Hg(II) ions. Electron microscopy reveals
      the formation of a spongy like structure on the adsorbent surface due to Hg(II)
      adsorption. Quantitative removal of mercury from hazardous effluents is
      demonstrated.

PMID- 18093729
TI  - Investigation of sewage sludge stabilization potential by the addition of fly ash
      and lime.
AB  - The aim of this work was the examination of stabilization potential of sewage
      sludge by the addition of fly ash and/or lime and the investigation of the effect
      of stabilization time on the properties of produced mixtures. Five samples were
      prepared by mixing fly ash, sewage sludge and lime in various ratios and the
      mixtures were stabilized for a period of 35 d. The addition of alkaline agents
      resulted in the increase of sample pH up to 12, the increase of total solids
      content to about 50% and the reduction of the organic fraction of the solids. The
      produced samples presented inhibition effects to seed germination and root length
      growth of three higher plants (one monocotyl and two dicotyls); however, samples
      with high sludge content resulted in negligible seed germination inhibition at
      prolonged stabilization times. The standard TCLP leaching procedure was applied
      in all the produced samples in order to evaluate the extraction potential of
      certain metallic elements; the content of metals in the eluates was varied,
      depending upon their speciation and form. Eluates presented significant
      inhibition to the marine photobacterium Vibrio fischeri bioluminescence, while
      the lowest inhibition was detected for the samples containing higher sludge
      content. These samples potentially could be applied as soil amendment, offering
      an efficient method for the combined utilization of two different solid wastes;
      however, low dosages of fly ash should be used for the production of a stabilized
      material presenting negligible effects with respect to its phytotoxic and
      ecotoxic properties.

PMID- 18093730
TI  - Prediction of mutagenic activity of nitronaphthalene isomers by infrared and
      Raman spectroscopy.
AB  - IR and Raman spectra of 1- and 2-nitronaphthalene isomers (1-NN and 2-NN) have
      been investigated to obtain more insight into the effect of the structure on
      mutagenic properties. To this purpose we have performed density functional theory
      calculations using B3LYP functional with cc-pVDZ basis set. The results have
      shown that IR and Raman spectra of nitronaphthalene isomers are somewhat similar
      to each other. A notable exception regards the symmetrical NO bonds stretching
      +CN bond stretching vibration (nusNO2+nuCN), which appears as very intense peak
      near 1350 cm(-1) in IR and Raman spectra of both isomers. Present calculations
      predict that for 2-NN isomer IR and Raman absorptions of this vibration are more
      intense by ca. 50 and 60%, respectively, than those of 1-NN isomer. The
      noticeably higher IR and Raman intensity values of the nusNO2+nuCN mode for 2-NN
      originate, respectively, from large dipole moment and polarizability changes with
      respect to the normal mode, suggesting that intermolecular interactions are
      especially favoured along this coordinate. These results are consistent with
      higher mutagenic activities of 2-NN in comparison to 1-NN isomer, supporting the
      binding to enzyme mechanism as a determining step in mutagenic pathways for this
      series of nitroaromatic compounds.

PMID- 18093731
TI  - SWOT analysis for safer carriage of bulk liquid chemicals in tankers.
AB  - The application of strengths, weaknesses, opportunities and threats (SWOT)
      analysis to formulation of strategy concerned with the safe carriage of bulk
      liquid chemicals in maritime tankers was examined in this study. A qualitative
      investigation using SWOT analysis has been implemented successfully for ships
      that are designed to carry liquid chemicals in bulk. The originality of this
      study lies in the use of SWOT analysis as a management tool to formulate
      strategic action plans for ship management companies, ship masters and officers
      for the carriage of dangerous goods in bulk. With this transportation-based SWOT
      analysis, efforts were made to explore the ways and means of converting possible
      threats into opportunities, and changing weaknesses into strengths; and strategic
      plans of action were developed for safer tanker operation.

PMID- 18093732
TI  - Effects of calcination temperatures on photocatalytic activity of SnO2/TiO2
      composite films prepared by an EPD method.
AB  - SnO2/TiO2 composite films were fabricated on transparent electro-conductive glass
      substrates (F-doped SnO2-coated glass:FTO glass) via an electrophoretic
      deposition (EPD) method using Degussa P25 as raw materials, and were further
      characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS),
      field emission scanning electron microscope (FESEM), UV-vis diffuse reflectance
      spectra and Photoluminescence spectra (PL). XRD and XPS results confirmed that
      the films were composed of TiO2 and SnO2. FESEM images indicated that the as
      prepared TiO2 films had roughness surfaces, which consisted of nano-sized
      particles. The effects of calcination temperatures on the surface morphology,
      microstructures and photocatalytic activity of SnO2/TiO2 composite films were
      further investigated. All the prepared SnO2/TiO2 composite films exhibited high
      photocatalytic activities for photocatalytic decolorization of Rhodamine-B
      aqueous solution. At 400 degrees C, the SnO2/TiO2 composite films showed the
      highest photocatalytic activity due to synergetic effects of low sodium content,
      good crystallization, appropriate phase composition and slower recombination rate
      of photogenerated charge carriers.

PMID- 18093733
TI  - Adsorptive removal of As(V) and As(III) from water by a Zr(IV)-loaded orange
      waste gel.
AB  - Orange waste, produced during juicing has been loaded with zirconium(IV) so as to
      examine its adsorption behavior for both As(V) and As(III) from an aquatic
      environment. Immobilization of zirconium onto the orange waste creates a very
      good adsorbent for arsenic. Adsorption kinetics of As(V) at different
      concentrations are well described in terms of pseudo-second-order rate equation
      with respect to adsorption capacity and correlation coefficients. Arsenate was
      strongly adsorbed in the pH range from 2 to 6, while arsenite was strongly
      adsorbed between pH 9 and 10. Moreover, equimolar (0.27 mM) addition of other
      anionic species such as chloride, carbonate, and sulfate had no influence on the
      adsorption of arsenate and arsenite. The maximum adsorption capacity of the
      Zr(IV)-loaded SOW gel was evaluated as 88 mg/g and 130 mg/g for As(V) and
      As(III), respectively. Column adsorption tests suggested that complete removal of
      arsenic was achievable at up to 120 Bed Volumes (BV) for As(V) and 8 0BV for
      As(III). Elution of both arsenate and arsenite was accomplished using 1 M NaOH
      without any leakage of the loaded zirconium. Thus this efficient and abundant bio
      waste could be successfully employed for the remediation of an aquatic
      environment polluted with arsenic.

PMID- 18093734
TI  - Enhanced sulfate reduction with acidogenic sulfate-reducing bacteria.
AB  - Sulfate reduction in a continuous flow, acidogenic reactor using molasses
      wastewater as the carbon source was studied at varying chemical oxygen
      demand/sulfate (COD/SO4(2-)) ratios. At a critical COD/SO4(2-) ratio of 2.7,
      neither COD nor sulfate were in excess for extra production of ethanol or acetate
      in the reactor. An acetic-type microbial metabolism was established with sulfate
      reducing bacteria (SRB) significantly consuming hydrogen and volatile fatty acids
      produced by acidogenic bacteria and hydrogen producing acetogens in degrading
      COD, thereby yielding sulfate removal rate>94.6%. A low critical COD/SO(4)2-
      ratio of 1.6 was also observed with the enriched ASRB population in reactor which
      overcomes the barrier to the treatment capability of sulfate-laden wastewater
      treatment with limited COD supply.

PMID- 18093735
TI  - The oxidative degradation of 2-mercaptobenzothiazole at the interface of beta
      MnO2 and water.
AB  - To investigate the oxidative degradation of organic pollutants at the interface
      of manganese oxides and water, beta-MnO2 was prepared and its crystal structure
      and the specific surface area were examined by X-ray diffraction (XRD) and
      Brunauer-Emmett-Teller (BET) methods, respectively. 2-Mercaptobenzothiazole (MBT)
      as a model chemical was used to study its oxidative degradation reaction in beta
      MnO2 suspension. The experimental results showed that MBT was effectively
      degraded and mineralized into SO4(2-) and NO3- by beta-MnO2. In the meantime, it
      was found that beta-MnO2 could be reductively dissolved, and aqueous and adsorbed
      Mn2+ was generated. The kinetics of MBT degradation by beta-MnO2 is a function of
      initial MBT concentration, beta-MnO2 dosage and pH value. At pH 4.6, apparent
      reaction orders with respect to initial MBT concentration and beta-MnO2 dosage
      were determined to be 0.88 and 0.27, respectively. The initial reaction rate
      (rinit) is of pH dependence with a reaction order of -0.36. The thermodynamics of
      MBT degradation by beta-MnO2 was also investigated, and the apparent activation
      energy was calculated to be 5.62 kJ/mol. The inhibited effect of carboxylic acids
      (oxalic, citric, tartaric, and malic acids) or metal ions (Ni2+, Ca2+, Mn2+ and
      Cr3+) on the oxidative degradation of MBT by beta-MnO2 was also investigated.
      This investigation will give some new insights for understanding the interaction
      of organic pollutants with manganese oxides in natural soils and sediments.

PMID- 18093736
TI  - Auditory task presentation reveals predominantly right hemispheric fMRI
      activation patterns during mental calculation.
AB  - Neuroimaging and lesion studies suggest that a network of different brain areas
      are involved in mental calculation processes. Indeed, little is known about the
      comparability of brain activation across studies because of the variety of
      different design parameters. The experiment reported in the present study
      examined response times and fMRI-BOLD activity patterns in normal volunteers for
      calculation tasks entailing addition, subtraction, multiplication and division
      tasks of different complexities from auditory stimulation. FMRI data showed
      activation patterns in bilateral superior frontal, adjacent to medial frontal
      regions, and in right precuneus as revealed by conjunction analysis. All other
      regional activations appeared to be operation-specific and distributed in
      predominantly right hemispheric frontal, parietal and central regions. It is
      concluded that both operation and task presentation modalities can have
      significant influence on the mobilization of regional neuronal networks required
      for mental calculation processes. Therefore, it is suggested that results from
      different studies should only be compared directly when analogous presentation
      modalities and operators were used in the applied experimental designs.

PMID- 18093737
TI  - The frequency, trajectories and predictors of adolescent recurrent pain: a
      population-based approach.
AB  - Recurrent pains are a complex set of conditions that cause great discomfort and
      impairment in children and adults. The objectives of this study were to (a)
      describe the frequency of headache, stomachache, and backache in a representative
      Canadian adolescent sample and (b) determine whether a set of psychosocial
      factors, including background factors (i.e., sex, pubertal status, parent chronic
      pain), external events (i.e., injury, illness/hospitalization, stressful-life
      events), and emotional factors (i.e., anxiety/depression, self-esteem) were
      predictive of these types of recurrent pain. Statistics Canada's National
      Longitudinal Survey of Children and Youth was used to assess a cohort of 2488 10-
      to 11-year-old adolescents up to five times, every 2 years. Results showed that,
      across 12-19 years of age, weekly or more frequent rates ranged from 26.1%-31.8%
      for headache, 13.5-22.2% for stomachache, and 17.6-25.8% for backache. Chi-square
      tests indicated that girls had higher rates of pain than boys for all types of
      pain, at all time points. Structural equation modeling using latent growth curves
      showed that sex and anxiety/depression at age 10-11 years was predictive of the
      start- and end-point intercepts (i.e., trajectories that indicated high levels of
      pain across time) and/or slopes (i.e., trajectories of pain that increased over
      time) for all three types of pain. Although there were also other factors that
      predicted only certain pain types or certain trajectory types, overall the
      results of this study suggest that adolescent recurrent pain is very common and
      that psychosocial factors can predict trajectories of recurrent pain over time
      across adolescence.

PMID- 18093739
TI  - Population dynamics of horn fly, Haematobia irritans irritans (L.) (Diptera:
      Muscidae), on Hereford cattle in Uruguay.
AB  - Abundance of adult horn flies, Haematobia irritans irritans (L.), was monitored
      on 25 untreated Hereford cows in Tacuarembo Department, Uruguay, during three
      consecutive grazing seasons, from October 1999 to May 2002. The population showed
      a variable pattern of abundance during three years, with peaks in late summer
      early fall of each year. Adult flies were continuously present, although in very
      low numbers in intervening winters. Numbers of flies per cow rarely exceeded a
      reference level of 200 flies per animal during the grazing season. Degree-day
      calculations indicated that approximately 12 generations were possible each year.
      Time series analysis of mean densities among consecutive generations indicated
      that population growth was governed by simple, direct density-dependence, with
      additional effects of seasonally varying weather. Response surface regressions
      confirmed that intergenerational growth was inversely related to mean density,
      and directly related to temperature. Stochastic simulations with the response
      surface model suggested that within the range of temperatures observed in our
      study, horn fly populations on Hereford cattle will tend toward densities of
      approximately 150 flies per animal in summer, and exceed a nominal level of 200
      flies per cow one or more times in about 65 of every 100 grazing seasons.

PMID- 18093738
TI  - Patient training in cancer pain management using integrated print and video
      materials: a multisite randomized controlled trial.
AB  - Standard guidelines for cancer pain treatment routinely recommend training
      patients to reduce barriers to pain relief, use medications appropriately, and
      communicate their pain-related needs. Methods are needed to reduce professional
      time required while achieving sustained intervention effectiveness. In a
      multisite, randomized controlled trial, this study tested a pain training method
      versus a nutrition control. At six oncology clinics, physicians (N=22) and nurses
      (N=23) enrolled patients (N=93) who were over 18 years of age, with cancer
      diagnoses, pain, and a life expectancy of at least 6 months. Pain training and
      control interventions were matched for materials and method. Patients watched a
      video followed by about 20 min of manual-standardized training with an oncology
      nurse focused on reviewing the printed material and adapted to individual
      concerns of patients. A follow-up phone call after 72 h addressed individualized
      treatment content and pain communication. Assessments at baseline, one, three,
      and 6 months included barriers, the Brief Pain Inventory, opioid use, and
      physician and nurse ratings of their patients' pain. Trained versus control
      patients reported reduced barriers to pain relief (P<.001), lower usual pain
      (P=.03), and greater opioid use (P<.001). No pain training patients reported
      severe pain (>6 on a 0-10 scale) at 1-month outcomes (P=.03). Physician and nurse
      ratings were closer to patients' ratings of pain for trained versus nutrition
      groups (P=.04 and <.001, respectively). Training efficacy was not modified by
      patient characteristics. Using video and print materials, with brief
      individualized training, effectively improved pain management over time for
      cancer patients of varying diagnostic and demographic groups.

PMID- 18093740
TI  - Gene expression profile analysis of epilepsy-associated gangliogliomas.
AB  - Gangliogliomas (GG) constitute the most frequent tumor entity in young patients
      undergoing surgery for intractable epilepsy. The histological composition of GG,
      with the presence of dysplastic neurons, corroborates their maldevelopmental
      origin. However, their histogenesis, the pathogenetic relationship with other
      developmental lesions, and the molecular alterations underlying the
      epileptogenicity of these tumors remain largely unknown. We performed gene
      expression analysis using the Affymetrix Gene Chip System (U133 plus 2.0 array).
      We used GENMAPP and the Gene Ontology database to identify global trends in gene
      expression data. Our analysis has identified various interesting genes and
      processes that are differentially expressed in GG when compared with normal
      tissue. The immune and inflammatory responses were the most prominent processes
      expressed in GG. Several genes involved in the complement pathway displayed a
      high level of expression compared with control expression levels. Higher
      expression was also observed for genes involved in cell adhesion, extracellular
      matrix and proliferation processes. We observed differential expression of genes
      as cyclin D1 and cyclin-dependent kinases, essential for neuronal cell cycle
      regulation and differentiation. Synaptic transmission, including GABA receptor
      signaling was an under-expressed process compared with control tissue. These data
      provide some suggestions for the molecular pathogenesis of GG. Furthermore, they
      indicate possible targets that may be investigated in order to dissect the
      mechanisms of epileptogenesis and possibly counteract the epileptogenic process
      in these developmental lesions.

PMID- 18093742
TI  - Pertussis toxin B-oligomer suppresses human immunodeficiency virus-1 Tat-induced
      neuronal apoptosis through feedback inhibition of phospholipase C-beta by protein
      kinase C.
AB  - Human immunodeficiency virus (HIV)-1 Tat is a multifunctional protein involved in
      viral replication, inflammation and apoptosis. Tat activates phospholipase C-beta
      (PLC-beta), presumably via a pertussis toxin (PTX) sensitive G(i) protein, which
      is critical for neuronal apoptosis. In this study, we show that Tat-mediated
      intracellular Ca(2+) release in rat pheochromocytoma (PC-12) cells and rat
      primary cortical neuronal cultures was abrogated by pretreatment with either
      pertussis toxin and/or its B-oligomer subunit (PTX-B), devoid of ADP
      ribosyltransferase activity. PTX-B pretreatment also inhibited intracellular
      Ca(2+) release by bradykinin and 2,4,6-trimethyl-N-(m-3-trifluoromethylphenyl)
      benzenesulfonamide (m-3M3FBS), a director activator of phospholipase C.
      Activation of protein kinase C (PKC) by phorbol 12,13-dibutyrate (PdBu) mimicked
      the PTX-B-mediated inhibition of m-3M3FBS-stimulated intracellular Ca(2+)
      increase, while inhibition of PKC by bisindolylmaleimide I hydrochloride (BIM)
      reversed the inhibitory action of PTX-B. Functionally, PTX-B reduced Tat-induced
      Bax and caspase-3 proteins and reduced cell apoptosis. We conclude that PTX
      inhibition of Tat-mediated intracellular Ca(2+) release is independent of ADP
      ribosylation of the G(i) protein via the A protomer, but mediated by the B
      oligomer. Furthermore, PTX-B suppresses HIV-1 Tat-mediated apoptosis by reducing
      its activation of PLC-beta through a PKC activation pathway.

PMID- 18093741
TI  - Platelet-derived growth factor-AA mediates oligodendrocyte lineage
      differentiation through activation of extracellular signal-regulated kinase
      signaling pathway.
AB  - Platelet-derived growth factor-AA (PDGF-AA) has been used as a potent mitogen for
      the proliferation of oligodendrocyte progenitor cells (OPCs). Whether it plays a
      role in oligodendrocyte lineage differentiation of neural stem cells (NSCs) is
      unclear. Here we report that PDGF-AA is an instructional signal required for the
      differentiation of embryonic forebrain NSCs into O4-positive oligodendrocytes.
      Moreover, such PDGF-AA-induced oligodendrocyte differentiation appears to be
      mediated by the extracellular signal-regulated kinases 1 and 2 (Erk1/2) but not
      phosphatidylinositol-3 kinase (PI3K) pathway. Finally, PDGF-AA treatment resulted
      in a significant increase in the expression of the oligodendrocyte-specific
      transcriptional factor Olig2 in an Erk1/2-dependent mechanism at early stages of
      oligodendrogliogenesis. Together, our studies provide cellular and molecular
      evidence to suggest that PDGF-AA is a key molecule that regulates the
      differentiation of embryonic NSCs into oligodendrocytes. The action of PDGF-AA is
      mediated by the activation of Erk pathway which involves the downstream
      upregulation of transcriptional factor Olig2.

PMID- 18093743
TI  - Regional adaptations in PSD-95, NGFI-A and secretogranin gene transcripts related
      to vulnerability to behavioral sensitization to amphetamine in the Roman rat
      strains.
AB  - Genetically selected for high or low two-way active avoidance, Roman high
      avoidance (RHA) and Roman low-avoidance (RLA) rats differ in their central
      dopaminergic activity, sensation/novelty- and substance-seeking profiles. These
      animals are, therefore, well suited to identify anatomical and neurochemical
      concomitants of behavioral sensitization, a phenomenon linked to addictive
      liability. We submitted inbred RHA (RHA-I), inbred RLA (RLA-I) and Sprague-Dawley
      OFA (SD-OFA) rats to a sensitization regimen with amphetamine and studied the
      behavioral response to an amphetamine challenge after a 2-week withdrawal period.
      The expression patterns of nerve growth factor inducible clone A (NGFI-A),
      secretogranin, post-synaptic density protein of 95 Kd (PSD-95), prodynorphin and
      proenkephalin mRNA were also analyzed using in situ hybridization, after the
      challenge with amphetamine. RHA-I rats showed stronger sensitization than SD-OFA
      rats. RLA-I rats did not show sensitization but were hyper-reactive to
      amphetamine. Expression of behavioral sensitization in RHA-I rats activated
      secretogranin and PSD-95 mRNA in the nucleus accumbens core. On the other hand,
      high induction of NGFI-A mRNA in the central amygdala was observed in RLA-I rats
      when they experienced amphetamine for the first time in the challenge. Our
      results reveal that 1) the acute locomotor response to amphetamine does not
      predict vulnerability to behavioral sensitization and 2) differences in
      vulnerability to sensitization may involve distinctive cellular adaptations at
      particular brain locations which may be related to addictive vulnerability.

PMID- 18093744
TI  - The olfactory conditioning in the early postnatal period stimulated neural
      stem/progenitor cells in the subventricular zone and increased neurogenesis in
      the olfactory bulb of rats.
AB  - The olfactory memory acquired during the early postnatal period is known to be
      maintained for a long period, however, its neural mechanism remains to be
      clarified. In the present study, we examined the effect of olfactory conditioning
      during the early postnatal period on neurogenesis in the olfactory bulb of rats.
      Using the bromodeoxyuridine-pulse chase method, we found that the olfactory
      conditioning, which was a paired presentation of citral odor (conditioned
      stimulus) and foot shock (unconditioned stimulus) in rat pups on postnatal day
      11, stimulated the proliferation of neural stem/progenitor cells in the anterior
      subventricular zone (aSVZ), but not in the olfactory bulb, at 24 h after the
      conditioning. However, the number of newborn cells in the olfactory bulb was
      increased at 2 weeks, but not 8 weeks, after such conditioning. Neither the
      exposure of a citral odor alone nor foot shock alone affected the proliferation
      of neural stem/progenitor cells in the aSVZ at 24 h after and the number of
      newborn cells in the olfactory bulb at 2 weeks after. The majority of newborn
      cells in the olfactory bulb of either the conditioned rats or the unconditioned
      rats expressed the neural marker NeuN, thus indicating that the olfactory
      conditioning stimulated neurogenesis in the olfactory bulb. These results suggest
      that olfactory conditioning during the early postnatal period temporally
      stimulates neurogenesis in the olfactory bulb of rats.

PMID- 18093746
TI  - The relation of IgM deposition to clinical parameters and histomorphometry in
      childhood mesangial proliferative glomerulonephritis.
AB  - We investigated the question of whether IgM deposition causes any difference in
      the histomorphometry of children with mesangial proliferative glomerulonephritis
      (MePGN). We retrospectively compared the urinalysis, blood pressure measurements,
      and serum creatinine levels of children with IgM (+) and IgM (-) MePGN. For
      histopathological evaluation, the outlines of Bowman's capsules and glomerular
      tufts of 10 glomeruli were rimmed manually, and the surrounded areas were
      calculated as pixels. The cells at each tuft of the largest four glomeruli were
      counted. Bowman's capsular areas, glomerular tuft areas, glomerular
      cellularities, and the number of cells per tuft area were determined for each
      patient. There were 24 (M/F: 14/10) patients with MePGN. Twelve of them were IgM
      (+). Mean age at biopsy was 6.8+/-4.1 years. IgM (+) patients mostly presented
      with nephrotic syndrome (NS) (n=9) and IgM (-) patients mostly with macroscopic
      hematuria (n=7). None of the clinical or laboratory findings was statistically
      different between the groups (p>0.05) except increased NS frequency in IgM (+)
      patients (p: 0.038). The histomorphometric parameters were similar in both groups
      (p>0.05). IgM (+) patients with MePGN mostly presented with NS in our study, but
      their histomorphometric parameters demonstrated no significant difference.

PMID- 18093745
TI  - Young adult non-daily smokers: patterns of alcohol and cigarette use.
AB  - Binge drinking and non-daily cigarette smoking are behaviors that are both
      problematic and prevalent in young adults. Although the relationship between
      drinking and daily smoking has been well categorized, the intersection between
      drinking and smoking in non-daily smokers has not been heavily researched. Past
      30-day and within-episode patterns of alcohol and cigarette use were collected in
      young adult non-daily smokers (N=40). Results demonstrated that 79% of smoking
      occurred on drinking days. Alcohol use was significantly greater on smoking days
      with the result that drinking to risky binge levels was more likely to occur on a
      smoking day. Smoking typically occurred after a certain level of alcohol pre-load
      (2.87 drinks). Together these results confirm that young adult non-daily smokers
      often concurrently use alcohol and cigarettes. Research is needed to identify
      possible mechanisms underlying the association between binge drinking and
      cigarette use in this vulnerable population.

PMID- 18093747
TI  - [Instrumental extractions using Thierry's spatulas: evaluation of the risk of
      perineal laceration according to occiput position in operative deliveries].
AB  - OBJECTIVE: Risk factors for severe perineal lacerations are nowadays well-known
      and they include operative vaginal deliveries and extractions in occiput
      posterior (OP) positions. The aim of this study was to assess whether OP position
      increases the risk for anal sphincter injury when compared with occiput anterior
      (OA) positions in operative deliveries using Thierry's spatulas. METHODS:
      Retrospective study of 163 extractions with Thierry's spatulas over a five-year
      period (January 2000 to December 2005) performed in a general hospital. Singleton
      cephalic pregnancies at term were studied and the incidence of severe perineal
      lacerations was noted in deliveries in OP and OA positions. RESULTS: In these 163
      cases, the varieties of presentation obtained by vaginal examination were 129 in
      anterior and 34 in posterior positions. Eleven posterior positions rotated
      anteriorly on delivery and 23 remained in a posterior position. The OA group
      (n=140) and the OP group (n=23) were constituted. Anal sphincter injury occurred
      significantly more often in the OP group compared with the OA group (17.4% versus
      2.9%, p=0.014) with an odds ratio of 7.1 (95% CI 1.6-31). Only one fourth-degree
      laceration was noted. Within the OP group, the incidence of vaginal lacerations
      was increased compared to the OA group, but without any significant difference
      (43.5% versus 27.9%, p=0.20). In a logistic regression model, the OP position was
      6.4 times (95% CI 1.3-31.5) more likely to be associated with anal sphincter
      injury than OA position. The incidence of OP position was 14.1% within the whole
      population studied and Thierry's spatulas permit anterior rotations of occipito
      posterior presentation in only 32.4% of cases. CONCLUSION: The efficiency of
      Thierry's spatulas is proven. As with forceps and vacuum extractors, extraction
      with Thierry's spatulas is a risk factor for perineal laceration compared to a
      spontaneous delivery. In deliveries with spatulas, OP head positions further
      increase this perineal risk against OA positions. OP positions before fetal
      extractions do not seem to be an ideal situation for using spatulas, even if an
      anterior rotation is achieved in one-third of cases.

PMID- 18093748
TI  - Pitch-related cues in the songs of sympatric mountain and black-capped
      chickadees.
AB  - Acoustic frequency (pitch) cues are known to be important in the recognition of
      conspecific song in a number of songbird species. Mountain chickadees (Poecile
      gambeli) and black-capped chickadees (Poecile atricapillus) are sympatric over
      parts of their ranges and their species-typical songs share many features. I
      examined the acoustic characteristics of song of these two congeners in a region
      of sympatry in southern Alberta, Canada. As reported for other populations in
      allopatry, black-capped chickadees emphasized relative frequency cues in song
      production. In particular, variation in the ratios between note frequencies was
      significantly less than variation in the note frequencies themselves. In
      contrast, songs of mountain chickadees did not have constant frequency ratios and
      contained an introductory acoustic element absent in black-capped chickadee song.
      Both species may rely on song note frequency or the presence of this introductory
      acoustic element when differentiating between conspecific song and heterospecific
      song. Song measures for chickadees in sympatry were similar to measures in
      allopatry, providing little evidence for character displacement in song
      production.

PMID- 18093749
TI  - Factor structure and diagnostic efficiency of the BDI-II in treatment-seeking
      substance users.
AB  - Screening instruments are needed to rapidly and efficiently identify depression
      in drug and alcohol users. The Beck Depression Inventory-Second Edition (BDI-II)
      has excellent validity in psychiatric, normative and primary care samples, but
      its diagnostic efficiency has not been examined in substance users. Using a large
      sample of treatment-seeking substance users and the Structured Clinical Interview
      for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV)
      to establish diagnosis, we examined the factor structure of the BDI-II and its
      ability to detect clinical depression, defined as the presence of a Major
      Depressive Disorder (MDD) or substance-induced depression. A three-factor
      structure provided the best fit, and the diagnostic efficiency of the BDI-II was
      moderate, and independent of gender and substance of abuse. Subscores had lower
      diagnostic efficiency than the BDI-II total score. A range of possible cutoff
      scores with corresponding sensitivity, specificity, positive predictive power and
      negative predictive power is provided to aid clinicians and researchers in
      choosing the optimal parameters for their screening needs.

PMID- 18093750
TI  - Smoking predicts posttraumatic stress symptoms among rescue workers: a
      prospective study of ambulance personnel involved in the Enschede Fireworks
      Disaster.
AB  - BACKGROUND: Examining whether smoking is a risk factor for posttraumatic stress
      disorder (PTSD) symptoms among rescue workers affected by a disaster. METHODS:
      Ambulance personnel (N=66) participated in surveys 2-3 weeks (T1) and 18 months
      after a fireworks disaster (T2). Hierarchical multiple regression analyses were
      conducted with cigarette consumption at T1 as a predictor of PTSD symptoms at T2.
      Demographic characteristics, disaster experiences, peritraumatic dissociation,
      intrusions and avoidance, psychological distress and alcohol consumption assessed
      at T1 were included as covariates. RESULTS: Regression analyses showed that
      smoking at T1 independently predicted intrusions, avoidance, hostility, and
      depression symptoms at T2. Results were not affected by controlling for post
      disaster critical incidents at work. CONCLUSIONS: This is the first prospective
      study among rescue workers demonstrating that smoking soon after a disaster
      predicts PTSD symptoms in the intermediate term. Findings substantiate results of
      previous studies indicating that smoking is a relevant risk factor. Future
      research on how changes in cigarettes consumption post-trauma affect risk of PTSD
      is required.

PMID- 18093751
TI  - College student use of Salvia divinorum.
AB  - OBJECTIVE: Salvia divinorum (salvia) is a plant that appears to be enjoying
      increased popularity as a legal hallucinogen in many U.S. jurisdictions. While
      the popular press has claimed that its use has become widespread, there have been
      no epidemiological studies published documenting this within the U.S. METHOD: A
      sample of college students was randomly drawn from a large public university in
      the southwestern U.S. and invited to participate in an online survey that
      included salvia use among a set of other drug use items. RESULTS: From the sample
      of 1516 college student respondents, a pattern of use emerged that indicates that
      salvia is indeed becoming a significant member of the list of drugs used, with
      4.4% of students reporting using salvia at least once within the past 12 months.
      Subpopulations that are typically most at risk for drug use within college
      students (Whites, males, fraternity members, heavy episodic drinkers) also were
      most likely to use salvia. CONCLUSIONS: The results indicate that more research
      is needed to determine the generalizability of these findings, and identify
      whether there are any negative consequences experienced either by the user or the
      community associated with this drug.

PMID- 18093752
TI  - Molecular cloning and sequence analysis of a novel zinc-metalloprotease gene from
      the Salinivibrio sp. strain AF-2004 and its extracellular expression in E. coli.
AB  - In this work the first protease gene encoding a novel zinc-metalloprotease from
      the moderately halophilic bacterium Salinivibrio sp. strain AF-2004 has been
      cloned, sequenced and reported to the GenBank. We have generated a library
      containing about 10,000 transformants whose screening yielded one clone harboring
      plasmid pBluescript with 3.6 kb inserted fragment (pBlueSVP2) with positive
      caseinolytic activity. Nucleotide sequence analysis of the selected clone
      revealed a single open reading frame (ORF) of 1833 bp encoding 611 amino acids.
      The deduced amino acid sequence includes a zinc-metalloprotease HEXXH-E consensus
      motif which is highly conserved in the M4 family of proteases. The primary amino
      acid sequence alignment search in the database revealed a moderate homology
      between the deduced amino acid sequence and the known zinc-metalloproteases
      including vibriolysin from Vibrio vulnificus and Pseudomonas aeruginosa elastase.
      The full length of SVP2 gene was subcloned into pQE-80L (pQEVP1) and transformed
      into Escherichia coli BL21 (DE3) for recombinant overexpression of the protease.
      Following induction by IPTG, active enzyme was found within cells and in the
      extracellular medium, where it slowly accumulated to high levels. Mass
      spectrometric fingerprinting of trypsin digested rSVP2 analysis identified the
      processed mature protease which starts at Ala-200 of a SVP2 full length protein.
      Although this result suggested a mature protein of 412 amino acids (44.8 kDa),
      electrospray-ionisation mass spectrometry revealed that the molecular mass of
      purified rSVP2 was only 34.2 kDa, which indicates a further cleavage site at the
      C-terminal.

PMID- 18093753
TI  - Evaluation of antibody-ELISA and real-time RT-PCR for the diagnosis and profiling
      of bluetongue virus serotype 8 during the epidemic in Belgium in 2006.
AB  - In 2006 bluetongue (BT) emerged for the first time in North-Western Europe.
      Reliable diagnostic tools are essential in controlling BT but data on the
      diagnostic sensitivity (Se) and specificity (Sp) are often missing. This paper
      aims to describe and analyse the results obtained with the diagnostics used in
      Belgium during the 2006 BT crisis. The diagnosis was based on a combination of
      antibody detection (competitive ELISA, cELISA) and viral RNA detection by real
      time RT-PCR (RT-qPCR). The performance of the cELISA as a diagnostic tool was
      assessed on field results obtained during the epidemic and previous surveillance
      campaigns. As the infectious status of the animals is unknown during an epidemic,
      a Bayesian analysis was performed. Both assays were found to be equally specific
      (RT-qPCR: 98.5%; cELISA: 98.2%) while the diagnostic sensitivity of the RT-qPCR
      (99.5%) was superior to that of the cELISA (87.8%). The assumption of RT-qPCR as
      standard of comparison during the bluetongue virus (BTV) epidemic proved valid
      based on the results of the Bayesian analysis. A ROC analysis of the cELISA,
      using RT-qPCR as standard of comparison, showed that the cut-off point with the
      highest accuracy occurred at a percentage negativity of 66, which is markedly
      higher than the cut-off proposed by the manufacturer. The analysis of the results
      was further extended to serological and molecular profiling and the possible use
      of profiling as a rapid epidemiological marker of the BTV in-field situation was
      assessed. A comparison of the serological profiles obtained before, during and at
      the end of the Belgian epidemic clearly showed the existence of an intermediate
      zone which appears soon after BTV (re)enters the population. The appearance or
      disappearance of this intermediate zone is correlated with virus circulation and
      provides valuable information, which would be entirely overlooked if only
      positive and negative results were considered.

PMID- 18093754
TI  - High prevalence of bovine papillomaviral DNA in the normal skin of equine sarcoid
      affected and healthy horses.
AB  - Bovine papillomavirus (BPV), the causative agent of papillomas in cattle, has
      been shown to play a major role in the pathogenesis of equine sarcoids in horses.
      BPV has also been detected occasionally in normal equine skin. In this study,
      presence and activity of BPV in normal skin and peripheral blood of 4 groups of
      horses were evaluated: sarcoid-affected horses, horses living in contact with
      sarcoid-affected horses, horses living in contact with papilloma-affected cattle
      and control horses. From each horse, 3 samples on 4 locations were collected: a
      swab of the intact skin surface and both a swab and a biopsy after
      decontamination. BPV DNA was found in the normal skin of 24 of 42 horses (57%).
      Mainly sarcoid-affected horses and horses living in contact with cattle were
      carriers (73%), but BPV DNA was also detected in 50% of the horses living in
      contact with sarcoid-affected horses and in 30% of the control population. BPV
      mRNA was detected in 58% of the samples positive for BPV DNA, although in a much
      lower quantity compared to sarcoids. In most of the BPV DNA positive samples mild
      acanthosis, slight basophilic cytoplasmic swelling of the epidermal layers and/or
      thickening of the basal membrane were noticed, but these observations were also
      present in several BPV DNA negative normal skin samples. BPV DNA could not be
      detected in peripheral blood. These findings suggest latent infection and a wide
      spread occurrence of BPV in the horse population.

PMID- 18093755
TI  - Bluetongue virus: European Community inter-laboratory comparison tests to
      evaluate ELISA and RT-PCR detection methods.
AB  - European Community national reference laboratories participated in two inter
      laboratory comparison tests in 2006 to evaluate the sensitivity and specificity
      of their 'in-house' ELISA and RT-PCR assays for the detection of bluetongue virus
      (BTV) antibodies and RNA. The first ring trial determined the ability of
      laboratories to detect antibodies to all 24 serotypes of BTV. The second ring
      trial, which included both antisera and EDTA blood samples from animals
      experimentally infected with the northern European strain of BTV-8, determined
      the ability of laboratories to detect BTV-8 antibodies and RNA, as well as the
      diagnostic sensitivity of the assays. A total of six C-ELISAs, six real-time RT
      PCR and three conventional RT-PCR assays were used. All C-ELISAs were capable of
      detecting the BTV serotypes currently circulating in Europe (BTV-1, 2, 4, 8, 9
      and 16), however some assays displayed inconsistencies in the detection of other
      serotypes, particularly BTV-19. All C-ELISAs detected BTV-8 antibodies in cattle
      and sheep by 21 dpi, while the majority of assays detected antibodies by 9 dpi in
      cattle and 8 dpi in sheep. All the RT-PCR assays were able to detect BTV-8,
      although the real-time assays were more sensitive compared to the conventional
      assays. The majority of real-time RT-PCR assays detected BTV RNA as early as 2
      dpi in cattle and 3 dpi in sheep. These two ring trails provide evidence that
      national reference laboratories within the EC are capable of detecting BTV
      antibodies and RNA and provide specificity and sensitivity information on the
      detection methods currently available.

PMID- 18093756
TI  - Influence of environmental conditions on biofilm formation by Hafnia alvei
      strains.
AB  - Hafnia alvei is considered an opportunistic pathogen of animal and humans,
      affecting a wide range of homeothermic and poikilothermic hosts with different
      body temperatures. In this work, H. alvei strains isolated from different sources
      were studied with regard to their capacity to form biofilms under different
      environmental conditions. Strain, growth phase, temperature and culture media
      dependent changes of biofilm formation were semiquantitatively monitored using a
      microtiter plate method. Our study shows that all strains used could form
      biofilms in vitro, and that biofilm formation increases dramatically during
      growth at 25 degrees C but not at 37 degrees C, and decreases at both
      temperatures in presence of glucose. At 16 degrees C only one strain isolated
      from a lizard was able to form a dense biofilm showing that the ability to form
      biofilms in this species is regulated by environmental factors and is also strain
      specific.

PMID- 18093757
TI  - Gross morphological changes of placentas associated with intrauterine growth
      restriction of fetuses: a case control study.
AB  - The present study aimed to throw light to any gross morphological changes of
      placenta that might contribute to the development of idiopathic IUGR. Gross
      examination of placentas from full-term uncomplicated pregnancies delivering
      singleton live IUGR babies, and live normal-weight babies (controls) were
      performed; then the results were compared. Fifty full-term freshly delivered
      placentas were collected both from normal deliveries and C.S. Twenty-eight (28)
      placentas were associated with IUGR and twenty-two (22) were from controls. The
      positions of insertion of the umbilical cords, placental weights, volumes and
      diameters were noted. These gross examinations revealed that the control
      placentas were bigger in diameters, had usual positions of insertion of umbilical
      cords, mean placental weight was 416.77 gm and mean placental volume was 343.86
      ml. In cases of IUGR placentas, there were some abnormal positions of insertion
      of umbilical cords in 11% placentas (marginal in 7.14% and velamentous in 3.57%),
      and placental weight and volume was significantly lower (p value<0.001). The
      placentas associated with IUGR were smaller in diameters than those of control
      group of placentas. The mean placental co-efficient of IUGR group in the present
      study was 0.156 (range 0.11-0.22) and that of the control group was 0.138 (range
      0.12-0.18). The greater placental co-efficient in IUGR indicates that although
      both placentas and babies in IUGR had less weight, placental sizes were not
      relatively less. In fact, these placentas were functional, and even tried to
      compensate the abnormal morphology. Therefore, though IUGR fetuses were more
      frequently associated with morphologically abnormal placentas, it could not be
      conclusively decided whether this abnormal gross morphology actually contributed
      to the intrauterine growth restriction.

PMID- 18093759
TI  - Validation of a menopause quality of life scale: the MENCAV scale.
AB  - OBJECTIVE: To assess the criterion validity, construct validity and test-retest
      reliability of the MENCAV menopause quality of life scale. METHODS:
      Observational, cross-sectional study covering a random sample of 470 women aged
      40-60 years. Two questionnaires were administered, namely, the MENCAV, made up of
      37 items in 5 dimensions, and the SF-36. A confirmatory factorial analysis was
      performed, leaving a final scale with 35 items. To evaluate criterion validity,
      the relationship between the physical and mental health dimensions of both
      instruments was estimated. Two experts assessed 40 menopausal women and recorded
      the correlations with the MENCAV. Construct validity was evaluated by comparing
      the mean scores of menopausal and non-menopausal women for each of the MENCAV
      dimensions. To assess test-retest reliability, we estimated the correlation
      between MENCAV scores when the questionnaire was administered on two separate
      occasions, 2 weeks apart. RESULTS: The final questionnaire comprised 35 items
      divided into 5 dimensions. All dimensions displayed high levels of reliability,
      with Cronbach's alpha values ranging from 0.71 to 0.91, and Cronbach's alpha for
      the total scale being 0.89. The intraclass correlation was 0.77 (95% CI: 0.61
      0.87). Correlations between the questionnaire and the SF-36 were significant; and
      those with the experts were significant for the physical, mental and sexual
      dimensions. CONCLUSIONS: The MENCAV is a valid and reliable questionnaire for
      assessing quality of life in menopausal women.

PMID- 18093760
TI  - Key functions in polymer carriers for intestinal absorption of insulin.
AB  - This work aimed to clarify the relationship between polymer function and insulin
      absorption, and to evaluate the optimized preparative formulation predicted from
      this relationship. Insulin-loaded polymer (ILP) carrier systems were prepared
      following a two-factor composite second-order spherical experimental design. To
      investigate the polymer function, we evaluated its insulin release,
      bioadhesiveness, and protective effect. Each ILP was administered intestinally,
      and glucose reduction was monitored as the pharmacological effect. Based on these
      data, an optimized formulation was predicted and how the polymer function affects
      insulin absorption was clarified by multivariate spline (MVS) interpolation. A
      greater pharmacological effect was apparent in ILPs with a smaller particle size
      and loaded with more insulin. The pharmacological effect predicted by MVS after
      the administration of ILP made under optimized preparative conditions was almost
      identical to the observed effect. Moreover, MVS clarified the relationship
      between the polymer function and the pharmacological effect. These results
      supported that MVS can be an effective tool with which to approximate the
      relationship between the function of a dosage form and its absorption, and to
      explore the optimized preparative conditions.

PMID- 18093761
TI  - UVA is the major contributor to the photodegradation of tretinoin and
      isotretinoin: Implications for development of improved pharmaceutical
      formulations.
AB  - The chemical stability of tretinoin (RA) and isotretinoin (13RA) in ethanol and
      dermatological cream preparations exposed to solar simulated light (SSL), UVA,
      and visible light has been studied. Photostability was monitored by an HPLC
      method that allowed simultaneous analysis of RA and 13RA, thus allowing
      photodegradation due to isomerization to other retinoids and photolysis to non
      retinoid products to be monitored. Both retinoids undergo both isomerization and
      photolysis following SSL, UVA and visible light exposure but RA is more sensitive
      to photodegradation than 13RA. Degradation of both retinoids by photolysis is
      considerably greater in cream formulations than in ethanol and the
      photodegradation follows second order kinetics. Rate constants and half-lives for
      degradation of RA and 13RA in ethanol solution and cream preparations subjected
      to different light sources are reported. The UVA component of SSL is the major
      contributor to photodegradation. Since UVA penetrates deeply into skin, our
      results suggest that photodegradation of RA may contribute to the
      photosensitivity associated with RA therapy. Our studies suggest that development
      of improved formulations and the use of effective UVA sunscreens may reduce the
      side effects of RA therapy.

PMID- 18093762
TI  - Preparation of amorphous indomethacin from aqueous 2,6-di-O-methyl-beta
      cyclodextrin solution.
AB  - Indomethacin precipitated exclusively in an amorphous form from aqueous 2,6-di-O
      methyl-beta-cyclodextrin solutions, whereas it precipitated in Form V polymorph
      from the solutions of the drug alone, parent cyclodextrins and 2-hydroxypropyl
      cyclodextrins. The polymorphic transition of the amorphous form to Form V
      crystals in aqueous solution was markedly inhibited by the addition of 2,6-di-O
      methyl-beta-cyclodextrin, keeping the amorphous state for at least 5 days at 4
      degrees C, whereas it quickly transformed to Form V crystals in the absence of
      2,6-di-O-methyl-beta-cyclodextrin. 2,6-Di-O-methyl-beta-cyclodextrin suppressed
      the solution-mediated polymorphic transition of amorphous form of indomethacin to
      Form V crystals in aqueous solution. The current results suggested that 2,6-di-O
      methyl-beta-cyclodextrin is useful for isolation of amorphous indomethacin that
      occurs at an early stage of crystallization according to "Ostwald's Rule of
      Stages".

PMID- 18093763
TI  - Understanding a relaxation behavior in a nanoparticle suspension for drug
      delivery applications.
AB  - Nanoparticle dispersion has demonstrated its effectiveness in improving the
      dissolution rate and oral bioavailability of poorly water-soluble compounds. When
      we studied the interactions of drug and polymeric stabilizers and milling
      parameters of a poorly water-soluble compound, Compound A, the relaxation
      behavior that occurred repeatedly in our nanoparticle dispersion formulation was
      observed. Nanomill was used to generate the nanoparticle dispersion, and milling
      parameters such as time, speed, and stabilizer loading were altered to
      investigate their effects on relaxation. The particle size and morphology of
      milled products were studied using a light-scattering particle analyzer and a
      scanning electron microscope (SEM). X-ray powder diffraction (XRD) was employed
      to characterize particle crystallinity and the crystallite size. The results
      indicated that, after milling, nanoparticles agglomerated constantly to form
      clusters and reached maximum apparent size within the first 24h. Thereafter, the
      clusters relaxed spontaneously and, within a few days, dissociated into
      individual primary particles and the suspension were stable at sub 100-nm levels
      near equilibrium. Milling crystalline drug substance resulted in an XRD pattern
      in which the peaks were observed to broaden, suggesting formation of disordered
      nanocrystalline. Altering milling conditions and stabilizer ratios influences the
      relaxation behavior and certainly led to optimization of the process and
      performance of nanoparticle suspension formulations.

PMID- 18093764
TI  - Skin permeation and metabolism of a new antipsoriatic vitamin D(3) analogue of
      structure 16-en-22-oxa-24-carboalkoxide with low calcemic effect.
AB  - A new vitamin D(3) analogue, SMD-429, is an antipsoriatic candidate of structure
      16-en-22-oxa-24-carboalkoxide exhibiting fewer side effects than known vitamin
      D(3) analogues. In this study, the permeation of SMD-429 through excised rat skin
      and three-dimensional cultured human skin model (LSE-high) was evaluated. The
      cumulative amount of SMD-429 permeated through the skin membranes was lower than
      that of either maxacalcitol or calcipotriol, whereas the amount of SMD-429 in the
      skin was the same. It was found from in vitro rat skin permeation experiment
      using [(3)H]SMD-429 that SMD-429 was permeated through skin mainly in its
      metabolized form. The skin permeation profiles of vitamin D(3) analogues obtained
      were analyzed based on a one-layer diffusion model to estimate permeation
      parameters. The apparent diffusion coefficient of SMD-429 was 1.30 x 10(-5)
      cm(2)/h, which was 10-fold lower than that of maxacalcitol. The apparent
      metabolic rate constant of SMD-429 in skin was 1.01 x 10(-1) h(-1), the same as
      maxacalcitol. Low apparent diffusivity of SMD-429 in skin might cause an increase
      in the probability of bioconversion. The same amount of SMD-429 in skin as known
      vitamin D(3) analogues would achieve sufficient therapeutic efficacy in skin.
      Such low skin permeability and high metabolic conversion in skin of SMD-429 would
      contribute to a reduction in the systemic side effects.

PMID- 18093765
TI  - A biodegradable drug delivery system for the treatment of postoperative
      inflammation.
AB  - Cataract surgery is often performed in patients suffering from associated
      pathologies. Our goal is to develop a biodegradable drug delivery system (DDS)
      combined with the artificial intraocular lens (IOL). DDS were manufactured using
      poly(D,L-lactide-co-glycolide), or PLGA, and were loaded with triamcinolone
      acetonide (TA). The loading capacity was approximately 1050 microg of TA per DDS.
      The higher the molecular weight of PLGA (34,000, 48,000 and 80,000Da), the slower
      was the release of TA in vitro. Cataract surgery was performed on the right eye
      of rabbits. IOL was inserted with (i) no DDS, (ii) unloaded DDS PLGA48000, (iii)
      one loaded DDS PLGA48000, (iv) two loaded DDS. The number of inflammatory cells
      and the protein concentration were measured in the aqueous humor (AH). Unloaded
      DDS showed good ocular biocompatibility. One DDS PLGA48000 loaded with TA
      significantly reduced postoperative ocular inflammation. Two loaded DDS PLGA48000
      was even more effective in inhibiting such inflammation. On long-term observation
      (days 63 and 84), reduction of inflammation could be obtained by insertion of one
      DDS PLGA48000 and a second DDS PLGA80000. Therefore, our "all in one" system is
      very promising since it could replace oral treatment and reduce the number of
      intraocular injections.

PMID- 18093766
TI  - Processing F0 with cochlear implants: Modulation frequency discrimination and
      speech intonation recognition.
AB  - Fundamental frequency (F0) processing by cochlear implant (CI) listeners was
      measured using a psychophysical task and a speech intonation recognition task.
      Listeners' Weber fractions for modulation frequency discrimination were measured
      using an adaptive, 3-interval, forced-choice paradigm: stimuli were presented
      through a custom research interface. In the speech intonation recognition task,
      listeners were asked to indicate whether resynthesized bisyllabic words, when
      presented in the free field through the listeners' everyday speech processor,
      were question-like or statement-like. The resynthesized tokens were
      systematically manipulated to have different initial-F0s to represent male vs.
      female voices, and different F0 contours (i.e. falling, flat, and rising)
      Although the CI listeners showed considerable variation in performance on both
      tasks, significant correlations were observed between the CI listeners'
      sensitivity to modulation frequency in the psychophysical task and their
      performance in intonation recognition. Consistent with their greater reliance on
      temporal cues, the CI listeners' performance in the intonation recognition task
      was significantly poorer with the higher initial-F0 stimuli than with the lower
      initial-F0 stimuli. Similar results were obtained with normal hearing listeners
      attending to noiseband-vocoded CI simulations with reduced spectral resolution.

PMID- 18093768
TI  - Relationship between loudness growth function and auditory steady-state response
      in normal-hearing subjects.
AB  - The present study investigates the relationship between auditory steady-state
      responses (ASSRs) and loudness growth function. ASSR amplitudes were compared to
      the perceived loudness level at frequencies of 500 and 2000Hz in 11 normal
      hearing subjects. As a first step, loudness growth function was estimated for the
      two test frequencies. Then ASSR amplitude was recorded for each of the two
      frequencies at different stimulus intensities, each corresponding to a loudness
      level as given by the first part of the study. Normalized results show that the
      ASSR amplitude correlates well with the loudness function (R(2)=0.81). A stepwise
      multiple linear regression confirmed these results with loudness explaining
      almost all the ASSR amplitude (loudness R(2)=0.81, p<0.001, f=562 and for
      intensity f=1.1, p=0.29). The non-linearity of the ASSR amplitude for low
      loudness levels can be explained by both the active amplification in the cochlea
      and the noise in the recording. The results suggest that ASSRs can be used for
      "objective" loudness measurement.

PMID- 18093767
TI  - Behavioral sensitivity to interaural time differences in the rabbit.
AB  - An important cue for sound localization and separation of signals from noise is
      the interaural time difference (ITD). Humans are able to localize sounds within 1
      2 degrees and can detect very small changes in the ITD (10-20micros). In
      contrast, many animals localize sounds with less precision than humans. Rabbits,
      for example, have sound localization thresholds of approximately 22 degrees .
      There is only limited information about behavioral ITD discrimination in animals
      with poor sound localization acuity that are typically used for the neural
      recordings. For this study, we measured behavioral discrimination of ITDs in the
      rabbit for a range of reference ITDs from 0 to +/-300micros. The behavioral task
      was conditioned avoidance and the stimulus was band-limited noise (500-1500Hz).
      Across animals, the average discrimination threshold was 50-60micros for
      reference ITDs of 0 to +/-200micros. There was no trend in the thresholds across
      this range of reference ITDs. For a reference ITD of +/-300micros, which is near
      the limit of the physiological window defined by the head width in this species,
      the discrimination threshold increased to approximately 100micros. The ITD
      discrimination in rabbits less acute than in cats, which have a similar head
      size. This result supports the suggestion that ITD discrimination, like sound
      localization [see Heffner, 1997. Acta Otolaryngol. 532 (Suppl.), 46-53] is
      determined by factors other than head size.

PMID- 18093769
TI  - Antimalarial activity of crude extracts from nine African medicinal plants.
AB  - An ethnobotanical study was conducted in Comores (Ngazidja) about plant species
      used traditionally for the treatment of various diseases, including malaria.
      Antimalarial activity of 76 vegetal extracts obtained from 17 species
      traditionally used to treat malaria symptoms, was evaluated in vitro using
      Plasmodium falciparum chloroquine-resistant strain (W2). Antiproliferative
      activity was evaluated on human monocytic THP1 cells and the selectivity index of
      the plant extracts was calculated. The results showed that 10 plant extracts had
      a moderate activity (5<IC(50)< or =10 microg/ml), and 6 a good in vitro activity
      with IC(50) value < or =5 microg/ml. The highest antiplasmodial activity was
      found for the MeOH/H(2)O leaves extract of Flueggea virosa (Roxb. Ex Willd.)
      Voigt subsp. virosa (Euphorbiaceae) (IC(50)=2 microg/ml), for roots decoction of
      Flueggea virosa (IC(50)=3 microg/ml) and for chloromethylenic roots extract of
      Vernonia colorata (Willd.) Drake subsp. grandis (DC.) C. Jeffrey (Asteraceae)
      (IC(50)=3 microg/ml). Three other extracts showed moderate antiplasmodial
      activity (IC(50)<5 microg/ml): Vernonia colorata (aerial part), Piper capense
      L.f. (Piperaceae), and Leptadenia madagascariensis Decne (Asclepiadaceae)
      chloromethylenic extracts (IC(50)=6 microg/ml; 7 microg/ml and 9 microg/ml,
      respectively). All the plants tested displayed a low cytotoxicity on THP1 cells.

PMID- 18093770
TI  - Pharmacological study of antispasmodic activity of Mirabilis jalapa Linn flowers.
AB  - INTRODUCTION: Mirabilis jalapa Linn is a well-studied plant. The indigenous
      people of Mexico use Mirabilis jalapa to cure many infirmities including
      dysentery, diarrhea, muscular pain and abdominal colic. In the present
      investigation, we have further characterized some pharmacological properties of
      an extract of Mirabilis jalapa flowers; therefore, we intend to contribute to
      understand the pharmacological effects and clarify the complex use of this
      medicinal plant. RESULTS: The extract of Mirabilis jalapa (1-1000 mug/mL)
      exhibits an inhibitory effect (IC(50)=18+/-0.7 micorg/mL) on gut smooth muscle
      contractility whereas it stimulates the contraction of rabbit aortic muscle
      (EC(50)=11.60+/-0.26 micorg/mL) in a concentration-dependent manner. CONCLUSIONS:
      These effects were not due to either ACh or HIS receptors blockage, IP(3), cAMP,
      cGMP, Ca(2+) release from intracellular storage, or protein kinase mediated
      contraction-relaxation mechanisms. The effects inducted by the Mirabilis jalapa
      extract may involve a serotoninergic mechanism, which, in turn, interacts with
      other adrenergic systems. Further studies are necessary to identify the active
      compounds within the extract and to elucidate the mechanism of action.

PMID- 18093771
TI  - Measuring knife stab penetration into skin simulant using a novel biaxial tension
      device.
AB  - This paper describes the development and use of a biaxial measurement device to
      analyse the mechanics of knife stabbings. In medicolegal situations it is typical
      to describe the consequences of a stabbing incident in relative terms that are
      qualitative and descriptive without being numerically quantitative. Here, the
      mechanical variables involved in the possible range of knife-tissue penetration
      events are considered so as to determine the necessary parameters that would need
      to be controlled in a measurement device. These include knife geometry, in-plane
      mechanical stress state of skin, angle and speed of knife penetration, and
      underlying fascia such as muscle or cartilage. Four commonly available household
      knives with different geometries were used: the blade tips in all cases were
      single-edged, double-sided and without serrations. Appropriate synthetic
      materials were used to simulate the response of skin, fat and cartilage, namely
      polyurethane, compliant foam and ballistic soap, respectively. The force and
      energy applied by the blade of the knife and the out of plane displacement of the
      skin were all used successfully to identify the occurrence of skin penetration.
      The skin tension is shown to have a direct effect on both the force and energy
      for knife penetration and the depth of out of plane displacement of the skin
      simulant prior to penetration: larger levels of in-plane tension in the skin are
      associated with lower penetration forces, energies and displacements. Less force
      and energy are also required to puncture the skin when the plane of the blade is
      parallel to a direction of greater skin tension than when perpendicular. This is
      consistent with the observed behaviour when cutting biological skin: less force
      is required to cut parallel to the Langer lines than perpendicularly and less
      force is required to cut when the skin is under a greater level of tension.
      Finally, and perhaps somewhat surprisingly, evidence is shown to suggest that the
      quality control processes used to manufacture knives fail to produce consistently
      uniform blade points in knives that are nominally identical. The consequences of
      this are that the penetration forces associated with nominally identical knives
      can vary by as much as 100%.

PMID- 18093772
TI  - Study of injuries combining computer simulation in motorcycle-car collision
      accidents.
AB  - This paper presents the approach of computer simulation to clarify the questions
      faced by forensic experts about what causes the various injuries characteristic
      of two motorcycle victims, including the motorcycle driver and the back seat
      occupant on the motorcycle, and how to exactly confirm which one of them is the
      motorcycle driver. Two typical motorcycle-car accident cases were reconstructed
      to analyze the movement and the load of both the motorcycle driver and the back
      seat occupant in the collision course. In case one, the back seat occupant
      suffered fatal head injuries when he fell on the ground after being thrown higher
      than the motorcycle driver over the top of the car. In case two, the compressive
      force loaded by the right tibia of the back seat occupant was larger and more
      durative compared with the motorcycle driver; the back seat occupant suffered a
      bursting fracture injury of his right tibia. These results might be useful for
      forensic experts in dealing with similar motorcycle-car collision accidents in
      the future.

PMID- 18093773
TI  - [Nontyphoidal Salmonella bacteremia cases in AIDS patients in a Dakar University
      Hospital (Senegal)].
AB  - OBJECTIVES: This study had for aim to describe epidemiological, clinical and
      bacteriological aspects of nontyphoidal Salmonella bacteremia in patients with
      AIDS in the Dakar University Hospital Infectious Diseases Clinic. METHOD: This
      study was made on data recorded between 1January1996 and 31December2005. The
      strains were identified according to biochemical (API 20E, BioMerieux) and
      antigenic features. Their susceptibility to antibiotic drugs was tested by
      antibiogram. Screening for strains secreting of an extended-spectrum
      betalactamase was performed. RESULTS: Sixty-two cases of nontyphoidal Salmonella
      bacteremia were recorded in AIDS patients as follows: Salmonellaenteritidis
      bacteremia (32 cases), Salmonellatyphimurium bacteremia (11 cases), and
      Salmonella spp bacteremia (11 cases). The strains were susceptible to
      ciprofloxacin, ceftriaxone, aztreonam, amoxicillin plus clavulanic acid in at
      least 92% of the cases. Only 79% of them were susceptible to cotrimoxazole. The
      lethality rate was 55%. DISCUSSION: This lethality rate of nontyphoidal
      Salmonella bacteremia is high in AIDS patients. Therefore, the priority should be
      put on prevention and, in patients with AIDS, on food hygiene measures,
      antiretroviral treatment and efficient chemoprophylaxis. This should prove
      efficient to reduce incidence of nontyphoidal Salmonella bacteremia.

PMID- 18093774
TI  - Health technology assessment of magnetic resonance imaging. Introduction.

PMID- 18093775
TI  - Health technology assessment of magnetic resonance imaging of the spine and bone
      marrow.
AB  - The high spatial resolution and the lack of ionizing radiation, makes magnetic
      resonance imaging the method of choice for imaging most spinal pathology,
      especially if associated with neurological symptoms. However, due to the high
      sensitivity of MR imaging, careful correlation between imaging findings and
      clinical findings is important to ensure appropriate treatment. Substituting
      radiographic evaluations for rapid MRI in the primary care setting may offer
      little additional benefit to patients. It may even increase the costs of care but
      the decisions about the use of imaging depend on judgments concerning whether the
      small observed improvement in outcome justifies additional cost. Because the
      presence of an abscess is a major factor in deciding between conservative and
      surgical treatment, MRI plays an essential role in the decision-making process
      concerning the treatment of spondylodiscitis. MR is also the method of choice for
      quantitative evaluation of bone marrow in lymphoma patients when a crucial
      therapeutic decision has to be made or for the qualitative evaluation of the
      spinal cord if compression is suspected in primary spinal malignancy or
      metastatic disease.

PMID- 18093776
TI  - CT and MR images of pleomorphic adenoma in major and minor salivary glands.
AB  - PURPOSE: To investigate the CT and MR imaging features of pleomorphic adenoma in
      the head and neck area. MATERIALS AND METHODS: Our materials of this study
      consisted of 50 pleomorphic adenomas from 50 patients which were all
      histopathologically diagnosed. The CT and MR images were retrospectively
      evaluated. The following features were evaluated: the detectability of the
      lesion, the tumor margin, the border of the lesion, the aspect of the lesion, the
      contrast between the lesion and surrounding tissue, the signal intensity of the
      lesion, the enhancement of contrast medium, the aspect of the lesion after the
      injection of contrast medium, the detectability of the capsule, and the
      detectability of bone resorption of the lesion. RESULTS: The tumor
      detectabilities were 77% on axial plain CT images and 90% on axial CE CT images,
      respectively. On CT images, pleomorphic adenoma tended to show a well-defined
      margin, a smooth border, an inhomogeneous aspect, a low or high contrast, and
      intermediate or high signal intensity. After contrast medium administration,
      pleomorphic adenoma tended to show a slightly high enhancement and either an
      inhomogeneous or a periphery enhancement on the CE CT images. The capsule could
      be hardly detected on CT images. The tumor detectabilities were 86% on axial T1
      weighted MR images, 88% on axial T2-weighted MR images, and 85% on axial CE T1
      weighted MR images, respectively. On MR images, pleomorphic adenomas tended to
      show well-defined margin, a lobulate border, an inhomogeneous aspect, a high
      contrast, and intermediate or high signal intensity. After contrast medium
      administration, pleomorphic adenoma tended to show a high enhancement and either
      an inhomogeneous or a periphery enhancement on MR images. The capsule could be
      detected in many cases on MR images. CONCLUSIONS: It was possible to detect the
      capsule in pleomorphic adenoma using MR images. The pleomorphic adenomas in head
      and neck area should be evaluated with MR images.

PMID- 18093777
TI  - Who wants cancer screening with PET? A contingent valuation survey in Japan.
AB  - OBJECTIVES: Cancer screening using whole-body fluorodeoxyglucose-positron
      emission tomography (FDG-PET) has gradually become popular in Japan. Although
      some studies have reported high cancer detection rates with PET screening, the
      justification for such an approach is still unclear, and no evidence has been
      provided to indicate that PET screening reduces cancer mortality. We measured the
      general public's willingness to pay (WTP) for this service using a contingent
      valuation method, after providing them with sufficient information regarding the
      efficacy and limitations of the service. METHODS: A computer-assisted
      questionnaire survey was conducted on males and females in Japan aged between 40
      and 59 years. The study participants (n=390) were provided with sufficient
      information about the PET procedure, the high cancer detection rate, false
      negatives/false-positives and the fact that the mortality-reducing effect of PET
      screening has not yet been demonstrated. The participants' WTP was ascertained by
      a double-bound dichotomous choice approach. RESULTS: The average WTP among all
      the participants was $68.0 (95% confidence interval: $56.9-79.2). A Weibull
      regression analysis showed that income, degree of concern about health, and
      family history of cancer were significant factors affecting WTP. CONCLUSIONS: The
      actual charge for PET screening in Japan is approximately $1000 on average, which
      is significantly higher than the participants' WTP for the actual benefit
      obtained from the service. If the Japanese healthcare consumers are well
      informed, most of them would avoid purchasing such a costly service.

PMID- 18093778
TI  - Simultaneous magnetic resonance imaging of diffusion anisotropy and diffusion
      gradient.
AB  - The theory of diffusion gradient-weighted MRI (DGWI) is presented in this paper.
      The Bloch-Torrey equation was modified to include the effect of intravoxel
      spatial-location variation of water diffusion (diffusion gradient) on MRI signal,
      in addition to the effect of intravoxel spatial-direction variation of water
      diffusion (diffusion anisotropy). An analytical solution for a diffusion-encoding
      spin-echo pulse sequence was derived. Unlike water diffusion which attenuates the
      image signal intensity, this newly derived solution relates the spatial gradient
      of the water diffusion with the phase of the image signal. This novel MRI
      technique directly measures both the water diffusion and its spatial gradient,
      and thus offers a noninvasive imaging tool to simultaneously investigate the
      intravoxel inhomogeneity and anisotropy of tissue structures. In addition, as
      demonstrated with our preliminary data, this new method may be utilized to
      delineate the interfaces of tissues with different diffusion. This method is an
      extension of the successful diffusion tensor MRI (DTI), but requires no
      additional data acquisition. In addition to the measured diffusion tensor, this
      new method provides measurements of the spatial derivatives of the three
      principal diffusivities of the tensor, thereby providing additional information
      for improving white matter fiber tractography.

PMID- 18093779
TI  - The optimal MR acquisition strategy for exponential decay constants estimation.
AB  - Estimating the relaxation constant of an exponentially decaying signal from
      experimental MR data is fundamental in diffusion tensor imaging, fractional
      anisotropy mapping, measurements of transverse relaxation rates and contrast
      agent uptake. The precision of such measurements depends on the choice of
      acquisition parameters made at the design stage of the experiments. In this
      report, chi(2) fitting of multipoint data is used to demonstrate that the most
      efficient acquisition strategy is a two-point scheme. We also conjecture that the
      smallest coefficient of variation of the decay constant achievable in any N-point
      experiment is 3.6 times larger than that in the image intensity obtained by
      averaging N acquisitions with minimal exponential weighting.

PMID- 18093780
TI  - Area of paradoxical signal drop after the administration of superparamagnetic
      iron oxide on the T2-weighted image of a patient with lymphangitic metastasis of
      the liver.
AB  - We report a geographic area of prominent hypointensity in T2-weighted images vs.
      normal adjacent liver parenchyma in a patient with cholangiocarcinoma and
      lymphangitic metastasis of the liver after superparamagnetic iron oxide (SPIO)
      administration. The area showing this prominent signal drop showed Kupffer cell
      proliferation and lymphangitic metastasis during a pathologic examination.

PMID- 18093781
TI  - Relaxation effects in the quantification of fat using gradient echo imaging.
AB  - Quantification of fat has been investigated using images acquired from multiple
      gradient echoes. The evolution of the signal with echo time and flip angle was
      measured in phantoms of known fat and water composition and in 21 research
      subjects with fatty liver. Data were compared to different models of the signal
      equation, in which each model makes different assumptions about the T1 and/or T2*
      relaxation effects. A range of T1, T2*, fat fraction and number of echoes was
      investigated to cover situations of relevance to clinical imaging. Results
      indicate that quantification is most accurate at low flip angles (to minimize T1
      effects) with a small number of echoes (to minimize spectral broadening effects).
      At short echo times, the spectral broadening effects manifest as a short apparent
      T2 for the fat component.

PMID- 18093782
TI  - Identification of low-molecular-weight protein (SCP1) from shark cartilage with
      anti-angiogenesis activity and sequence similarity to parvalbumin.
AB  - Cartilage was considered as a possible natural source of anti-angiogenesis
      compounds due to its known avascular nature. In this study, a low-molecular
      weight protein with an anti-angiogenesis activity was isolated from shark
      cartilage using a mild extraction procedure. The protein was purified to
      homogeneity by gel filtration and electroelution techniques and its N-terminal
      amino acid sequence was determined. The purified protein, designated as SCP1,
      represented a molecular weight of 13.7 kDa, pI of 6.9-7 and its N-terminal
      sequence revealed sequence similarity to alpha parvalbumin family. The protein
      inhibited angiogenesis when subjected to microvessel sprouting of collagen
      embedded rat aortic ring assay. It is suggested that SCP1 could be considered as
      a new angiogenesis inhibitor derived from shark cartilage.

PMID- 18093783
TI  - Spectroscopic and chromatographic characterization of triflusal delivery systems
      prepared by using supercritical impregnation technologies.
AB  - This study describes the development and evaluation of an analytical method for
      the characterization of triflusal (2-acetoxy-4-(trifluoromethyl) benzoic acid)
      dispersed in sustained delivery systems prepared using supercritical fluid
      impregnation technology. Characterization assays comprised the determination of
      the percentage of triflusal and its degradation product impregnated in polymeric
      supports and further monitoring of the releases of the two drug components over
      time in physiological conditions. Preliminary delivery profiles were monitored
      spectrophotometrically using a continuous-flow system. In this case, no selective
      wavelength for discriminating between triflusal and metabolite was found so that
      measurements at 225 nm provided overall profiles corresponding to the two
      compounds. For a more accurate study, a chromatographic method was developed for
      monitoring the evolution of the concentration of the two components
      independently. Triflusal and metabolite were separated in a C(18) column and 25
      mM acetic acid/acetate (pH 5.0)+methanol (40/60v/v) mobile phase. Several
      triflusal-polymer samples were prepared under different experimental conditions
      and release features were evaluated. Excellent delivery systems were obtained
      with poly(methyl)methacrylate beads treated at 40 degrees C and 190 bar for 48 h
      using supercritical carbon dioxide as a solvent. These samples showed a constant
      sustained release of drug for several weeks.

PMID- 18093784
TI  - Simultaneous determination and pharmacokinetics of five bufadienolides in rat
      plasma after oral administration of Chansu extract by SPE-HPLC method.
AB  - A sensitive and rapid solid-phase extraction-high performance liquid
      chromatography (SPE-HPLC) method has been developed for the determination of five
      bufadienolides, arenobufagin, teliocinobufagin, cinobufotalin, cinobufagin and
      resibufogenin in rat plasma and applied to a pharmacokinetic study in rats after
      oral administration of Chansu extract (Venenum Bufonis). Plasma samples were
      pretreated with solid-phase extraction using Extract-Clean cartridges, and the
      extracts were analyzed by a reversed-phase C(18) column on a HPLC system with
      photodiode array detection (DAD). The calibration curves were linear over the
      range of 0.10-1.66 microg/ml for arenobufagin, 0.03-1.20 microg/ml for
      telocinobufagin, 0.01-0.62 microg/ml for cinobufotalin, 0.03-0.70 microg/ml for
      cinobufagin and 0.02-2.57 microg/ml for resibufogenin, respectively. The limit of
      quantification was 1.1 ng/ml for arenobufagin, 0.3 ng/ml for telocinobufagin, 9.7
      ng/ml for cinobufotalin, 8.8 ng/ml for cinobufagin, 7.7 ng/ml for resibufogenin,
      respectively. The established method could be easily applied to the determination
      and pharmacokinetic studies of five bufadienolides in rat plasma after oral
      administration of Chansu extract.

PMID- 18093785
TI  - Evaluation of 5'-MGB hybridization probes for detection of Bordetella pertussis
      and Bordetella parapertussis using different real-time PCR instruments.
AB  - Rapid and accurate tests capable of distinguishing Bordetella pertussis from
      milder Bordetella parapertussis infection can aid in treating patients. We
      evaluated a novel real-time polymerase chain reaction (PCR) method that allows
      rapid and accurate diagnosis and distinction between B. pertussis and B.
      parapertussis infections. The method is based on a fluorescent 5'-minor groove
      binding molecule hybridization probe that can clearly distinguish between B.
      pertussis and B. parapertussis by post-PCR melt curve analysis. The reagents
      worked equally well in several different real-time PCR instruments. The
      Bordetella detection reagents are combined with internal control components to
      account for PCR inhibition without compromising assay sensitivity.

PMID- 18093786
TI  - NFAT signaling in neural development and axon growth.
AB  - The NFAT (nuclear factor of activated T-cells) family of transcription factors
      functions as integrators of multiple signaling pathways by binding to chromatin
      in combination with other transcription factors and coactivators to regulate
      genes central for many developmental systems. Recent experimental evidence has
      shown that the calcineurin/NFAT signaling pathway is important in axonal growth
      and guidance during vertebrate development. In fact, studies with triple
      NFATc2/c3/c4 mutant mice demonstrate that the extension and organization of
      sensory axon projection and commissural axon growth are both dependent upon NFAT
      activity. Neurotrophin and L-type calcium channel signaling modulate
      intracellular calcium levels to regulate the nuclear import and transcriptional
      activity of NFAT by activating the phosphatase calcineurin. The rephosphorylation
      and subsequent export of NFAT from the nucleus is mediated by several kinases,
      including GSK-3beta, which contribute to the fine tuning of NFAT transcriptional
      activity in neurons. However, currently, no direct transcriptional targets for
      NFAT have been identified in a chromatin environment in the nervous system.
      Undiscovered are also the binding partners of NFAT that might combinatorially
      regulate specific genes important for neuronal development. This review will
      discuss the current knowledge related to NFAT signaling in the nervous system
      development and the potential for future research directions.

PMID- 18093788
TI  - Interactive and evaluative correlates of dialogue sequence: a simulation study
      applying the RIAS to turn taking structures.
AB  - OBJECTIVE: This study explores novel characterizations of turn taking structure
      and its interaction and evaluative correlates. METHODS: The Roter Interaction
      Analysis System (RIAS) was applied to videotapes of 51 physicians with a
      simulated patient (SP) to create a variety of novel turn taking measures
      including turn frequency, rate of interactivity, density, duration, and statement
      pacing. RESULTS: Visits averaged 52 speaker turns with an interactivity rate of
      3.9 turns per visit minute. For physicians, turn duration averaged 13.7 s with a
      turn density of 4.2 statements paced at one statement every 3 s. For the SP, turn
      duration was 3 s with a turn density of 1.4 statements paced at one statement
      every 2 s. More turns, briefer turn duration and faster physician pacing were
      significantly related to positive ratings of affective demeanor, interpersonal
      satisfaction and collaborative decision-making. These measures, and
      interactivity, were also associated with a RIAS-based patient-centeredness score
      and more overall patient talk. CONCLUSION: Turn taking structures can be
      characterized in novel ways lending depth and richness to our understanding of
      dialogue, relationships to the patient-centeredness of a visit, and evaluative
      judgments of physician performance. PRACTICE IMPLICATIONS: The study findings
      suggest specificity to the interviewing admonishment "talk less and listen more"
      by enhancing the interactivity of the dialogue and guarding against doctors
      tendency toward long monologues.

PMID- 18093789
TI  - A single candle.

PMID- 18093787
TI  - Cognitive control in autism spectrum disorders.
AB  - Cognitive control refers to the ability to flexibly allocate mental resources to
      guide thoughts and actions in light of internal goals. Given the behavioral
      inflexibility exhibited by individuals with autism spectrum disorders (ASDs), it
      would appear they experience cognitive control deficits. Cognitive correlates of
      this behavioral inflexibility have been elusive in previous investigations. Study
      goals were to investigate deficits in cognitive control in ASDs; to explore its
      developmental trajectory; and to test whether control deficits are related to
      symptoms of inflexible thoughts and/or behaviors, and attention symptoms. Thirty
      one children and adolescents aged 8-17 with ASDs and 32 age, IQ, and gender
      matched control subjects completed cognitive, diagnostic, and behavorial
      assessments, as well as a measure of cognitive control involving overcoming a
      prepotent response tendency. Compared with typically developing control subjects,
      individuals with ASDs exhibited deficits in cognitive control. Younger children
      with ASDs did not demonstrate age-related improvements in cognitive control.
      Modest relationships between cognitive control, IQ, and attention problems were
      found for the sample. Only the relationship between cognitive control and full
      scale IQ survived correction for multiple comparisons.

PMID- 18093790
TI  - A game for smokers: a preliminary naturalistic trial in a psychiatric hospital.
AB  - OBJECTIVE: "Pick-Klop" is a game based on cognitive behavioral therapy. It aims
      to change smokers' attitudes towards tobacco addiction. This study tests the
      feasibility and the impact of one brief session of the intervention in a
      naturalistic setting within a psychiatric hospital. METHOD: Fifty-one smokers
      were recruited during their stay in a psychiatric hospital with a prohibitive
      smoking policy. They were assessed pre- and post-treatment with visual analogue
      scales designed to evaluate their intention to stop smoking. RESULTS: All
      patients completed the intervention. The outcome shows that the intention to stop
      smoking becomes significantly stronger after the intervention. CONCLUSION: This
      pilot study supports the feasibility and the effectiveness of the "Pick-Klop"
      game in a psychiatric hospital setting. The game seems to improve the intention
      to quit smoking. The data, however, should be confirmed by a controlled trial.
      Moreover, follow-up studies are needed to examine the potential impact of the
      game on smoking cessation attempts. PRACTICAL IMPLICATIONS: The game seems to be
      a useful and simple tool for education about smoking in a psychiatric hospital
      setting.

PMID- 18093791
TI  - Feedback in patient counselling training--pharmacy students' opinions.
AB  - OBJECTIVE: The aims were to analyse Finnish pharmacy students' opinions of
      feedback given to them in patient counselling training during their internship
      period, and to evaluate the guidelines used. METHODS: The study was based on
      reports written by 136 students, analysed qualitatively. To examine the
      significance of the guidelines and the perceived quality of the feedback,
      students were categorised into groups. Correlations were assessed by frequencies
      and cross-tabulations. RESULTS: A statistically significant correlation was found
      (p<0.001) between the perceived quality of the feedback and the use of the
      guidelines. The relations between the perceived usefulness of the guidelines and
      the use of the guidelines in patient counselling exercises were also
      statistically significant (p=0.034). CONCLUSIONS: The results indicate that the
      perceived quality of the feedback was indeed associated with the use of the
      guidelines. They not only offer a training method focusing on essential
      communication skills in patient counselling, but are also a useful tool for
      developing counselling practices in general. PRACTICAL IMPLICATIONS: Since
      mentors are probably unfamiliar with the guidelines, students should be trained
      to explain their use. To ensure that mentors are competent in analysing
      communication skills, further training for them is essential.

PMID- 18093792
TI  - Plasma homocysteine is a determinant of tissue necrosis factor-alpha in
      hypertensive patients.
AB  - Chronic sub-clinical inflammation observed in hypertension plays a prominent role
      in the progression of atherosclerosis. Accumulating evidence suggests that
      homocysteine (Hcy) can cause inflammation. The aim of this study was to compare
      the predictive utility of Hcy and lipid measures as determinants of inflammation
      in hypertensive patients. We studied a group of 100 patients (45.0+/-12.2 years
      old) with essential hypertension and a control group of 40 healthy volunteers
      (44.0+/-8.7 years old). We found that plasma total Hcy (tHcy), tumor necrosis
      factor alpha (TNF-alpha), interleukin 6 (IL-6), and C-reactive protein (CRP) were
      significantly higher in hypertensive patients compared with the control group.
      The subgroup of hypertensive patients with obesity had higher levels of TNF-alpha
      (p<0.001), IL-6 (p<0.01), and tHcy (p=0.063), compared with the subgroup of
      hypertensive patients without obesity. The subgroup of patients with a history of
      myocardial infarction or stroke had significantly higher levels of tHcy, TNF
      alpha, IL-6, and CRP compared to patients with a negative history of vascular
      events. In the group of hypertensive patients, a strong positive correlation
      between tHcy and TNF-alpha was observed (r=0.48; p<0.001). In contrast, no
      correlation was observed between TNF-alpha and any of the lipid measures. In
      multivariate regression analysis tHcy, but not lipids, was an independent
      predictor of TNF-alpha. In conclusion, our findings show that plasma tHcy is a
      determinant of TNF-alpha in hypertension and that obesity or a history of
      vascular events aggravates inflammation in patients with hypertension. A positive
      correlation between Hcy and TNF-alpha suggests a mechanism underlying the pro
      atherogenic properties of Hcy.

PMID- 18093793
TI  - SPG/IND-induced septic shock in a LPS-low responder strain, C3H/HeJ mice.
AB  - The administration of beta-glucan (sonifilan; SPG) in combination with a non
      steroidal anti-inflammatory drug, indomethacin (IND), induced lethal septic shock
      in mice. To demonstrate the influence of bacterial lipopolysaccharide (LPS) in
      this lethal toxicity, LPS non-responder C3H/HeJ mice were used to compare
      features of sepsis and physicochemical parameters in the present study. The
      administration of SPG and IND induced the death of C3H/HeJ mice, lowering rectal
      temperature, reducing body weight, increasing serum tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-6 (IL-6) levels, shortening the gastrointestinal
      tract, and increasing the GOT/GPT level. Microbial translocation to various
      organs was also significantly increased. These results strongly suggested that
      LPS-non-responding strain also induced septic shock in this experimental model,
      and other pathogen-associated molecular patterns (PAMPs) may significantly
      contribute to the septic shock.

PMID- 18093794
TI  - Microencapsulation decreases the skin absorption of N,N-diethyl-m-toluamide
      (DEET).
AB  - The insect repellent N,N-diethyl-3-methylbenzamide (DEET) is widely used and is
      generally regarded as safe when used according to label instructions. Yet many
      studies have shown it to be absorbed through the skin. The objective of this
      study was to determine whether the skin absorption rate of DEET could be
      decreased while maintaining an evaporation rate consistent with effective
      repellency. To this end, an aqueous suspension containing 14C-DEET (15%w/w)
      entrapped in walled polysaccharide microcapsules was prepared and tested for skin
      absorption in vitro using modified Franz cells maintained in a fume hood. The
      control formulation was 15%w/w DEET in ethanol. Two doses (3 microL and 5 microL
      per 0.79 cm2 cell) of each formulation were applied to split-thickness human
      cadaver skin (n=8/dose), and permeation was monitored for 24h. The
      microencapsulated DEET formulation lead to a 25-35% reduction of radiolabel
      permeation compared to the ethanolic DEET formulation. Skin levels of
      radioactivity at 24h were comparable, indicating that DEET evaporation from the
      microencapsulated formulation was comparable to or greater than that from
      ethanol. Hence microencapsulation increased the ratio of DEET evaporation rate to
      skin penetration rate relative to unencapsulated control in this in vitro study.

PMID- 18093795
TI  - Antioxidant and antimutagenic properties of the monoterpene indole alkaloid
      psychollatine and the crude foliar extract of Psychotria umbellata Vell.
AB  - Psychollatine is a monoterpene indole alkaloid produced and accumulated by
      Psychotria umbellata Vell. (Rubiaceae) leaves in relatively high amounts
      (approximately 3% of the dry weight). The alkaloid has been shown to display
      opioid-like analgesic, anxiolytic, antidepressive and antipsychotic activities in
      rodents. In vitro assays suggested a protective role for this molecule in plant
      oxidative stress responses. This work reports antioxidant properties of
      psychollatine and the crude foliar extract from P. umbellata in strains of
      Saccharomyces cerevisiae proficient and deficient in antioxidant defenses exposed
      to H2O2 and paraquat. The antimutagenic activity of P. umbellata and its main
      alkaloid were assayed in S. cerevisiae N123 strain in presence of H2O2. Moreover,
      the antioxidant capacity of these substances on the hydroxyl radical (OH.) was
      investigated, using the hypoxanthine/xanthine oxidase assay. Psychollatine and
      the crude foliar extract of P. umbellata showed protective effect against
      oxidative stress in yeast, acting both as antioxidant and antimutagenic agents.

PMID- 18093796
TI  - Alterations in episodic memory in patients with systemic lupus erythematosus.
AB  - The purpose of this paper was to examine memory performance in patients with SLE
      by studying the overall deterioration in memory, analyzing the differences and
      frequency of impairment in the variables from the visual and verbal memory tests,
      and studying the alterations in the memory. This study included 59 patients with
      a diagnosis of systemic lupus erythematosus (SLE) and 18 with a diagnosis of
      chronic discoid lupus (CDL), who were administered the Spanish complutense verbal
      learning test (TAVEC) and the Rey complex figure test (RCFT). Statistically
      significant differences were detected between the two groups on the immediate
      visual recall and delayed visual recall variables, with the mean of the SLE group
      being lower than that of the CDL group. The difference between the frequency of
      verbal and visual impairment could be explained by various factors, one of which
      would be a lateralization of memory impairment.

PMID- 18093797
TI  - An updated version of the Weigl discriminates adults with dementia from those
      with mild impairment and healthy controls.
AB  - Dementia screening batteries often fall short on measures of executive
      functioning. The Weigl Color Form Sorting Test (WCFST) is a candidate for
      inclusion in such batteries, but can be insensitive to mild disturbance. The
      WCFST consists of 12 colored geometric shapes and requires the patient to sort
      the pieces by color or form, and then shift to the other sorting principle
      unassisted. We created a modified version of the WCFST (the Weigl-R) with
      increased conceptual complexity by adding two stimulus dimensions (texture and
      central shapes). The range of scores was also increased by adding the extent of
      examiner assistance required to achieve a correct sort, ability to verbalize
      conceptual strategy, and number of perseverations. We administered the Weigl-R to
      a group of 30 patients with mixed dementias, 34 adults with cognitive impairment
      without dementia, and 21 healthy controls. The new measure discriminated well
      between healthy controls and older adults with either cognitive impairment
      without dementia, or dementia. The Weigl-R may be a useful adjunct to brief
      dementia batteries but requires further validation.

PMID- 18093798
TI  - Media exposure and dimensions of anxiety sensitivity: differential associations
      with PTSD symptom clusters.
AB  - The present investigation examined the impact of anxiety sensitivity (AS) and
      media exposure on posttraumatic stress disorder (PTSD) symptoms. Reactions from
      143 undergraduate students in Hamilton, Ontario were assessed in the Fall of 2003
      to gather information on anxiety, media coverage, and PTSD symptoms related to
      exposure to a remote traumatic event (September 11th). Regression analyses
      revealed that the Anxiety Sensitivity Index (ASI; [Peterson, R. A., & Reiss, S.
      (1992). Anxiety Sensitivity Index manual, 2nd ed. Worthington, Ohio:
      International Diagnostic Systems]) and State-Trait Anxiety Inventory trait form
      (STAI-T; [Spielberger, C. D., Gorsuch, R. L., & Lushene, R. E. (1970). State
      trait anxiety inventory. Palo Alto, California: Consulting Psychologists Press])
      total scores were significant predictors of PTSD symptoms in general. The ASI
      total score was also a significant predictor of hyperarousal and avoidance
      symptoms. Subsequent analyses further demonstrated differential relationships
      based on subscales and symptom clusters. Specifically, media exposure and trait
      anxiety predicted hyperarousal and re-experiencing symptoms, whereas the ASI fear
      of somatic sensations subscale significantly predicted avoidance and overall PTSD
      symptoms. Implications and directions for future research are discussed.

PMID- 18093799
TI  - Toxicity testing in the 21st century: a vision and a strategy.
AB  - Advances in molecular biology, biotechnology, and other fields are paving the way
      for major improvements in how scientists evaluate the health risks posed by
      potentially toxic chemicals found at low levels in the environment. These
      advances would make toxicity testing quicker, less expensive, and more directly
      relevant to human exposures. This National Research Council report creates a far
      reaching vision for the future of toxicity testing.

PMID- 18093800
TI  - Occupational and environmental exposures to heavy metals: risk factors for male
      infertility in Lebanon?
AB  - A case-control study was conducted to examine whether occupational or
      environmental exposures, particularly to heavy metals, are associated with male
      infertility in Lebanon, a war-torn country with a history of environmental
      degradation. Seventy-four infertile cases and 76 fertile controls were selected
      from 2 major fertility clinics in Beirut. Data collection involved risk-factor
      interviews, semen analysis, and blood collection for heavy metal analysis.
      Multiple regression analysis showed that men with reported occupational exposures
      were twice as likely to be infertile as unexposed men. However, none of the
      subcategories of infertile men (based on semen analysis results) had
      significantly higher whole blood concentrations of heavy metals when compared to
      fertile controls. Blood concentrations were well within the range for referent
      populations of healthy individuals. Thus, despite Lebanon's poor record of
      occupational and environmental stewardship, exposure to metal pollutants does not
      appear to represent an important risk factor for male infertility.

PMID- 18093801
TI  - The unimodal model for the classification of ordinal data.
AB  - Many real life problems require the classification of items into naturally
      ordered classes. These problems are traditionally handled by conventional methods
      intended for the classification of nominal classes where the order relation is
      ignored. This paper introduces a new machine learning paradigm intended for multi
      class classification problems where the classes are ordered. The theoretical
      development of this paradigm is carried out under the key idea that the random
      variable class associated with a given query should follow a unimodal
      distribution. In this context, two approaches are considered: a parametric, where
      the random variable class is assumed to follow a specific discrete distribution;
      a nonparametric, where the random variable class is assumed to be distribution
      free. In either case, the unimodal model can be implemented in practice by means
      of feedforward neural networks and support vector machines, for instance.
      Nevertheless, our main focus is on feedforward neural networks. We also introduce
      a new coefficient, r(int), to measure the performance of ordinal data
      classifiers. An experimental study with artificial and real datasets is presented
      in order to illustrate the performances of both parametric and nonparametric
      approaches and compare them with the performances of other methods. The
      superiority of the parametric approach is suggested, namely when flexible
      discrete distributions, a new concept introduced here, are considered.

PMID- 18093802
TI  - Differential mediation of the Wnt canonical pathway by mammalian Dishevelleds-1, 
      2, and -3.
AB  - In the Drosophila, a single copy of the phosphoprotein Dishevelled (Dsh) is
      found. In the genomes of higher organism (including mammals), three genes
      encoding isoforms of Dishevelled (Dvl1, Dvl2, and Dvl3) are present. In the fly,
      Dsh functions in the Wnt-sensitive stabilization of intracellular beta-catenin
      and activation of the Lef/Tcf-sensitive transcriptional response known as the Wnt
      "canonical" pathway. In the current work we explore the expression of
      Dishevelleds in mammalian cells and provide an estimate of the relative cellular
      abundance of each Dvl. In mouse F9 cells, all three Dvls are expressed. Dvl2
      constitutes more than 95% of the total pool, the sum of Dvl1 and Dvl3
      constituting the remainder. Similarly, Dvl2 constitutes more than 80% of the Dvl1
      3 pool in mouse P19 and human HEK 293 cells. siRNA-induced knock-down of
      individual Dvls was performed using Wnt3a-sensitive canonical pathway in F9 cells
      as the read-out. Activation of the canonical signaling pathway by Wnt3a was
      dependent upon the presence of Dvl1, Dvl2, and Dvl3, but to a variable extent.
      Wnt3a-sensitive canonical transcription was suppressible, by knock-down of Dvl1,
      Dvl2, or Dvl3. Conversely, the overexpression of any one of the three Dvls
      individually was found to be capable of promoting Lef/Tcf-sensitive
      transcriptional activation, in the absence of Wnt3a, i.e., overexpression of
      Dvl1, Dvl2, or Dvl3 is Wnt3a-mimetic. Graded suppression of individual Dvl
      isoforms by siRNA was employed to test if the three Dvls could be distinguished
      from one another with regard to mediation of the canonical pathway. Canonical
      signaling was most sensitive to changes in the abundance of either Dvl3 or Dvl1.
      Changes in expression of Dvl2, the most abundant of the three isoforms, resulted
      in the least effect on canonical signaling. Dvl-based complexes were isolated by
      pull-downs from whole-cell extracts with isoform-specific antibodies and found to
      include all three Dvl isoforms. Rescue experiments were conducted in which
      depletion of either Dvl3 or Dvl1 suppresses Wnt3a activation of the canonical
      pathway and the ability of a Dvl isoform to rescue the response evaluated. Rescue
      of Wnt3a-stimulated transcriptional activation in these siRNA-treated cells
      occurred only by the expression of the very same Dvl isoform depleted by the
      siRNA. Thus, Dvls appear to function cooperatively as well as uniquely with
      respect to mediation of Wnt3a-stimulated canonical signaling. The least abundant
      (Dvl1, 3) plays the most obvious role, whereas the most abundant (Dvl2) plays the
      least obvious role, suggesting that individual Dvl isoforms in mammals may
      operate as a network with some features in common and others rather unique.

PMID- 18093804
TI  - Putative progenitor/stem cells isolated from human oral mucosa are resistant to
      ionizing radiation.

PMID- 18093803
TI  - Assessment of single and bound features in a working memory task in
      schizophrenia.
AB  - If disturbance of binding in long term memory is well established in
      schizophrenia, data concerning working memory maintenance are less clear. Feature
      binding in working memory was investigated in 19 patients with schizophrenia and
      19 healthy controls. Binding was assessed by comparing two conditions in which
      participants had to retain four letters and four spatial locations. These
      features were presented either bound or separate. Results showed that both groups
      had better performances for bound than separate features, despite the fact that
      patients performed significantly worse than controls. When maintenance for
      isolated features was assessed, patients were severely disturbed for spatial
      locations but not for letters. Such a result suggests that reduced working memory
      performance in patients with schizophrenia for bound features is probably a
      consequence of a spatial deficit rather than a specific deficit of the binding
      process. Thus, not all form of binding are disturbed in schizophrenia.

PMID- 18093805
TI  - The IVth International Symposium on Epidermolysis Bullosa, Santiago, Chile, 27-29
      September 2007.

PMID- 18093806
TI  - Cloning and expression of genes involved in conidiation and surface properties of
      Penicillium camemberti grown in liquid and solid cultures.
AB  - Based on bioinformatic data on model fungi, the rodA and wetA genes encoding,
      respectively, a RodA hydrophobin protein and the WetA protein involved in
      conidiation mechanisms, were PCR-cloned and characterized for the first time in
      Penicillium camemberti. These results, completed by a sequence of the brlA gene
      (available in GenBank), which encodes a major transcriptional regulator also
      involved in the conidiation mechanism, were used to compare, by qRT-PCR, the
      expression of the three genes in liquid and solid cultures in a synthetic medium.
      While expression of the brlA and wetA genes increased dramatically in both
      culture conditions after 4 days of growth, expression of the rodA gene increased
      only with conidiation and in the solid culture, and this expression was
      correlated with production and secretion of a RodA protein outside the hyphae,
      which became very hydrophobic. In liquid cultures, no production of RodA occurred
      in mycelia, which remained hydrophilic, and no conidiation was detected despite
      formation of swellings at the tips of hyphae. The absence of conidiation in
      liquid culture correlated with the lack of rodA gene expression, which could be
      regulated by the medium composition independently of brlA and wetA genes
      expression.

PMID- 18093807
TI  - Preliminary evidence of nitazoxanide activity on Toxocara canis in a mouse model.

PMID- 18093808
TI  - A role of D domain-related proteins in differentiation and migration of embryonic
      cells in Xenopus laevis.
AB  - We have characterized a cDNA clone, rdd (repeated D domain-like), that encodes
      for a secretory protein consisting of repeated domains of cysteine-rich sequence.
      Whole-mount in situ hybridization analysis revealed that rdd2, rdd3 and rdd4 are
      transiently expressed in the ventral and lateral mesoderm and the overlying
      ectoderm at the late gastrula and tailbud stages. Morpholino oligonucleotide (MO)
      was used to inhibit the translation of endogenous rdd3 and rdd4, and we found
      that the circulation of red blood cells completely disappears in the MO-injected
      tadpoles. Histological analysis showed that formation of the ventral aorta,
      dorsal aorta and posterior cardinal vein in the trunk region was severely
      disorganized in these animals. Injection of MO affected the expression of alpha
      globin, a terminal differentiation marker of red blood cells, but did not affect
      the expression of scl, flk-1 or tie-2, suggesting that angiopoietic and
      hematopoietic precursor cells differentiate normally in the rdd-depleted embryo.
      The transplantation of labeled tissues followed by tracing of the donor cells
      revealed a role of rdds in migration of the embryonic angioblasts and myeloid
      cells. These observations first demonstrate the role of the novel cysteine-rich
      proteins in migration of the embryonic cells.

PMID- 18093810
TI  - Regulation of silica morphology by proteins serving as a template for
      mineralization.
AB  - The fabrication of inorganic materials under the control of biopolymers is a
      research field of tremendous interest because in diatoms and sponges the specific
      proteins direct the formation of silica at ambient conditions that have highly
      organized structure at multiple length scales and properties that the material
      scientists can only aspire to achieve. Here it is demonstrated by using a novel
      biocompatible precursor that common proteins - albumin, caseins and gelatin - can
      mediate formation of hybrid nanocomposite materials through catalyzing the sol
      gel processes and templating silica generated in situ. Serving as the template,
      the proteins provide a unique opportunity to regulate the silica morphology and
      properties by means of a change of their secondary and tertiary structure through
      pH and temperature.

PMID- 18093809
TI  - Neural systems for executive and emotional processing are modulated by symptoms
      of posttraumatic stress disorder in Iraq War veterans.
AB  - The symptom-provocation paradigms generally used in neuroimaging studies of
      posttraumatic stress disorder (PTSD) have placed high demands on emotion
      processing but lacked cognitive processing, thereby limiting the ability to
      assess alterations in neural systems that subserve executive functions and their
      interactions with emotion processing. Thirty-nine veterans from Iraq and
      Afghanistan underwent functional magnetic resonance imaging while exposed to
      emotional combat-related and neutral civilian scenes interleaved with an
      executive processing task. Contrast activation maps were regressed against PTSD
      symptoms as measured by the Davidson Trauma Scale. Activation for emotional
      compared with neutral stimuli was highly positively correlated with level of PTSD
      symptoms in ventral frontolimbic regions, notably the ventromedial prefrontal
      cortex, inferior frontal gyrus, and ventral anterior cingulate gyrus. Conversely,
      activation for the executive task was negatively correlated with PTSD symptoms in
      the dorsal executive network, notably the middle frontal gyrus, dorsal anterior
      cingulate gyrus, and inferior parietal lobule. Thus, there is a strong link
      between the subjectively assessed behavioral phenomenology of PTSD and objective
      neurobiological markers. These findings extend the largely symptom provocation
      based functional neuroanatomy to provide evidence that interrelated executive and
      emotional processing systems of the brain are differentially affected by PTSD
      symptomatology in recently deployed war veterans.

PMID- 18093811
TI  - Mechanical properties of hexadecane-water interfaces with adsorbed hydrophobic
      bacteria.
AB  - This study focuses on how intact, hydrophobic bacteria in their stationary (i.e.,
      non-dividing) phase could adsorb onto the hexadecane-water interface and alter
      its mechanical properties. The two strains of bacteria used in forming the
      interfacial films were Acinetobacter venetianus RAG-1 and Rhodococcus
      erythropolis 20S-E1-c. Using the dynamic pendant drop technique, the film
      interfacial tension was monitored as the surface area was made to undergo
      transient changes. Under static conditions, both types of bacteria had no effect
      on the interfacial tension. When subjected to transient excitations, however, the
      two bacterial films exhibited clear and qualitatively similar rheological
      properties: they responded as two-dimensional Maxwellian materials when the
      interfacial areas were dilated suddenly, but appeared to be purely elastic upon
      rapid area compression. Such rheological behaviours are "non-linear" in that the
      responses of the tension to area dilation and contraction are not mirror images
      of one another. Despite their qualitative similarities, the two types of film had
      very distinct film elasticities and relaxation times. The most striking
      difference between the two bacterial films was revealed under continuous
      reduction of area, when the A. venetianus RAG-1 system displayed a "paper-like"
      interface, whereas the interface of the R. erythropolis 20S-E1-c system was "soap
      film-like". These macroscopic observations could be explained by the surface
      ultrastructures of the two cell strains determined using transmission electron
      microscopy.

PMID- 18093812
TI  - Simultaneous electrochemical determination of three sunscreens using
      cetyltrimethylammonium bromide.
AB  - This paper proposes a methodology based on electrochemical reduction for the
      simultaneous determination of three sunscreen agents, namely 4-methylbenzylidene
      camphor (MBC), benzophenone-3 (BENZO) and 2-ethylhexyl-4-methoxycinnamate (EHMC)
      by differential-pulse polarography (DPP). The highest peak currents and optimal
      separation of reduction peaks were obtained by using a supporting electrolyte
      consisted of Britton-Robinson buffer-methanol (8:2) solution at pH 4.0 and
      cationic surfactant 3.0 x 10(-4)mol L(-1) cetyltrimethylammonium bromide (CTAB).
      The methodology was validated using four commercial sunscreen preparation as a
      sample and the results showed high recovery rates. The efficiency of the proposed
      methodology was demonstrated by comparing the results obtained by DPP with those
      obtained by the high-performance liquid chromatography (HPLC) method.

PMID- 18093813
TI  - Time and chemotherapy treatment trends in the treatment of elderly patients
      (age>or=70 years) with non-small cell lung cancer.
AB  - AIMS: Palliative chemotherapy in non-small cell lung cancer (NSCLC) has been
      established since 1995 and little chemotherapy treatment was given to these
      patients before 1990. This retrospective study investigates the treatment outcome
      of elderly patients (age>or=70 years) with NSCLC over the past 13 years in a
      large UK cancer centre. MATERIALS AND METHODS: A comparison of all-cause survival
      between the time periods 1990-1994, 1995-1999 and 2000-2004 was adjusted for age,
      gender, stage and performance status. A comparison of survival was also made
      between three age groups: 70-74, 75-79 and 80+ years. RESULTS: Between 1990 and
      2004, 302 patients>or=70 years had NSCLC. There were differences in age and
      performance status between the time periods. There was no improvement in median
      survival between the three time periods (P=0.6). There was little difference in
      outcome between the three age cohorts. CONCLUSIONS: The analysis shows that there
      has been no significant improvement in survival for elderly patients with
      advanced lung cancer treated with chemotherapy in the past 13 years.

PMID- 18093814
TI  - Histological outcome of delayed orchidectomy after primary chemotherapy for
      metastatic germ cell tumour of the testis.
AB  - AIMS: To identify the incidence of viable local tumour in the testis of patients
      undergoing delayed orchidectomy after initial presentation with advanced germ
      cell tumour (GCT) treated by primary chemotherapy. PATIENTS AND METHODS: Thirty
      three patients presenting with advanced metastatic GCT were reviewed. The median
      age at presentation was 34 years. All received chemotherapy without previous
      orchidectomy. The decision to initiate chemotherapy without orchidectomy was
      based on a heavy tumour load and the patient's condition at initial presentation.
      A histological diagnosis was available from a biopsy of metastases in 23
      patients; treatment in the remaining 10 patients was initiated after diagnosis
      based on a combination of elevated serum tumour markers, testicular findings and
      the presence of a retroperitoneal mass. RESULTS: Seminomatous GCT (SGCT) was
      diagnosed in 13 patients, non-seminomatous GCT (NSGCT) in 17 patients and mixed
      GCT (MGCT) in the remaining three patients. Bleomycin/etoposide/cisplatin-based
      chemotherapy was the principle regimen. After initial chemotherapy, all patients
      with pure SGCT had only scar tissue in the orchidectomy specimen, with no
      residual tumour. Nine of 17 patients (52.9%) with NSGCT had viable tumour
      remaining in the orchidectomy specimen. All three cases of MGCT had persistent
      viable invasive seminoma. Twenty-seven patients (81.8%) were recurrence free and
      alive after a median of 49 months of follow-up. CONCLUSIONS: Thirty-six per cent
      of patients had residual tumour locally in the testis after primary chemotherapy
      for metastatic GCT of the testis. However, in the cases with pure seminomatous
      disease, there was no residual tumour present. It may not be necessary to
      undertake delayed orchidectomy in these patients.

PMID- 18093815
TI  - Differentially expressed pro- and anti-apoptogenic genes in response to benzene
      exposure: Immunohistochemical localization of p53, Bag, Bad, Bax, Bcl-2, and Bcl
      w in lung epithelia.
AB  - Benzene, a well-known human carcinogen, is a commonly used industrial chemical
      that evokes further toxicological concern because of its potential genotoxic
      risks as a constituent of petrol and the byproduct of combustion and cigarette
      smoke. The present study investigated the effects of benzene inhalation on the
      expression of pro- and antiapoptogenic genes in lung epithelia.
      Immunohistochemical expression was assessed for antiapoptotic Bcl-2 family
      proteins, including Bcl-2, Bcl-w, and Bag-1 as well as proapoptotic subfamily
      members with Bcl-2 homology (BH)1 1-3, namely Bax, those that consist of only the
      BH3 region, represented by Bad, and proapoptotic gene expression for p53. Rats
      exposed to benzene via inhalation (300 ppm) for 7 days showed a significant
      upregulation of proapoptotic gene expression for p53, Bax, and Bad as assessed by
      a semiquantitative segmental analysis of the lung epithelia, including
      bronchioles, terminal bronchioles, respiratory bronchioles, and alveoli. Bag-1,
      an antiapoptogenic gene, was also found to have significant upregulated
      expression in lung epithelia. Since the underlying mechanisms by which Bag-1
      exerts its antiapoptogenic effects are not known, benzene may target the protein
      chaperones hsc70/hsp70, or RING finger protein associated with Bag-1 activity.
      Alternatively, the significant downregulation of Bcl-2 may have diminished the
      antiapoptotic synergism necessary for the effectiveness of Bag-1. Both Bcl-2 and
      Bcl-w were found to be significantly downregulated compared to the proapoptotic
      counterparts. These data support the role of benzene in activating proapoptogenic
      events that lead to the upregulation of gene expression that may provide a
      crucial defense mechanism within lung parenchyma to reduce mutation hazard and
      potential carcinogenic effects of benzene-initiated pathogenesis.

PMID- 18093816
TI  - COX-2 and CCR2 induced by CD40 ligand and MCP-1 are linked to VEGF production in
      endothelial cells.
AB  - Recent studies have reported that expression of MCP-1 and its receptor, CCR2; and
      CD40-CD40 ligand (CD40L) interaction on mesenchymal cells play important roles in
      tumor development. Studies have also connected MCP-1, CCR2, and CD40L to COX-2
      expression. The aim of this study was to examine the effect of MCP-1/CCR2 and
      CD40-CD40L interaction on COX-2 and VEGF expression in endothelial cells. We also
      investigated the localization of these proteins in gastric cancer tissue. COX-2
      and CCR2 levels were evaluated in CD40L-stimulated HUVECs by Western blot and
      real-time PCR. VEGF secreted in the culture media was quantified by ELISA.
      Localizations of MCP-1, CD40L, CD34, CD40 and CCR2 in 34 gastric cancer tissue
      specimens were evaluated by immunohistochemistry. CD40-CD40L interaction-induced
      COX-2 production and subsequently, upregulated COX-2 production contributed to
      elevated VEGF and CCR2 levels in CD40L-stimulated HUVECs. CD40L-stimulated VEGF
      production was COX-2 but not COX-1 dependent. RS-102895, a CCR2-specific
      antagonist, significantly reduced VEGF production in CD40L- and MCP-1-stimulated
      HUVECs. MCP-1 had a synergistic effect on COX-2, CCR2 and VEGF levels in CD40L
      stimulated HUVECs. In gastric cancer tissue, there was significant correlation
      between microvessel density and scores for CD40L, MCP-1 and CCR2 protein
      expression. Thus, MCP-1 had a synergistic effect on COX-2 and CCR2 protein
      expression in CD40L-stimulated HUVECs and thereby stimulated VEGF production in
      these cells.

PMID- 18093817
TI  - Sex, but not maternal protein or folic acid intake, determines the fatty acid
      composition of hepatic phospholipids, but not of triacylglycerol, in adult rats.
AB  - The aim of the study was to investigate whether the protein and folic acid
      content of the maternal diet and the sex of the offspring alter the
      polyunsaturated fatty acid content of hepatic phospholipids and triacylglycerol
      (TAG). Pregnant rats were fed diets containing 18% or 9% protein with either 1 or
      5mg/kg folic acid. Maternal diet did not alter hepatic lipid composition in the
      adult offspring. Data from each maternal dietary group were combined and
      reanalysed. The proportion of 18:0, 20:4n-6 and 22:6n-3 in liver phospholipids
      was higher in females than in males, while hepatic TAG composition did not differ
      between sexes. Delta5 Desaturase expression was higher in females than in males.
      Neither Delta5 nor Delta6 desaturase expression was related to polyunsaturated
      fatty acid concentrations. These results suggest that sex differences in liver
      phospholipid fatty acid composition may reflect primary differences in the
      specificity of phospholipid biosynthesis.

PMID- 18093818
TI  - Sorbents for CO2 capture from high carbon fly ashes.
AB  - Fly ashes with high-unburned-carbon content, referred to as fly ash carbons, are
      an increasing problem for the utility industry, since they cannot be marketed as
      a cement extender and, therefore, have to be disposed. Previous work has explored
      the potential development of amine-enriched fly ash carbons for CO2 capture.
      However, their performance was lower than that of commercially available
      sorbents, probably because the samples investigated were not activated prior to
      impregnation and, therefore, had a very low surface area. Accordingly, the work
      described here focuses on the development of activated fly ash derived sorbents
      for CO2 capture. The samples were steam activated at 850 degrees C, resulting in
      a significant increase of the surface area (1075 m2/g). The activated samples
      were impregnated with different amine compounds, and the resultant samples were
      tested for CO2 capture at different temperatures. The CO2 adsorption of the
      parent and activated samples is typical of a physical adsorption process. The
      impregnation process results in a decrease of the surface areas, indicating a
      blocking of the porosity. The highest adsorption capacity at 30 and 70 degrees C
      for the amine impregnated activated carbons was probably due to a combination of
      physical adsorption inherent from the parent sample and chemical adsorption of
      the loaded amine groups. The CO2 adsorption capacities for the activated amine
      impregnated samples are higher than those previously published for fly ash
      carbons without activation (68.6 vs. 45 mg CO2/g sorbent).

PMID- 18093819
TI  - Blends of HDPE wastes: study of the properties.
AB  - In this work we have analysed the properties of blends of recycled high-density
      polyethylene (HDPE) filled with talc. We have used two kinds of polymer matrices.
      The first one came entirely from ground injection moulded parts whereas the
      second was bimodal, incorporating 80% of the previous HDPE and 20% of recycled
      HDPE coming from bottles. We have also used two kinds of commercial talc
      characterized by a medium particle size of 2 microm and 10 microm, respectively.
      The amount of talc added to both matrices weighed of 10% and 20%. With regards to
      the mechanical properties of the analysed composites, greater values of Young's
      modulus and break stresses were found using a smaller particle size and higher
      talc content. On the other hand, the combination of the two HDPEs with very
      different viscosities produced a notable increase in the strain at break and in
      the absorbed energy; both measured at high and low strain rates. Despite the
      differences in viscosities between the two HDPEs, we did not observe separation
      of phases during either the processing or testing. Under impact loading, the
      higher energy absorption in the composites was observed when the finest talc
      grade with a 10% content weight was added to the bimodal matrix.

PMID- 18093820
TI  - Air pollution control residues from waste incineration: current UK situation and
      assessment of alternative technologies.
AB  - Current disposal options for APC residues in the UK and alternative treatment
      technologies developed world-wide have been reviewed. APC residues are currently
      landfilled in the UK where they undergo in situ solidification, although the
      future acceptability of this option is uncertain because the EU waste acceptance
      criteria (WAC) introduce strict limits on leaching that are difficult to achieve.
      Other APC residue treatment processes have been developed which are reported to
      reduce leaching to below relevant regulatory limits. The Ferrox process, the VKI
      process, the WES-PHix process, stabilisation/solidification using cementitious
      binders and a range of thermal treatment processes are reviewed. Thermal
      treatment technologies convert APC residues combined with other wastes into inert
      glass or glass-ceramics that encapsulate heavy metals. The waste management
      industry will inevitably use the cheapest available option for treating APC
      residues and strict interpretation and enforcement of waste legislation is
      required if new, potentially more sustainable technologies are to become
      commercially viable.

PMID- 18093821
TI  - A super highly sensitive glucose biosensor based on Au nanoparticles
      AgCl@polyaniline hybrid material.
AB  - Gold nanoparticles (AuNPs) with an average diameter of 5nm were assembled on the
      surface of silver chloride@polyaniline (PANI) core-shell nanocomposites
      (AgCl@PANI). Attenuated total reflection Fourier transform infrared spectroscopy
      (ATR-FTIR) suggested that AuNPs were incorporated on AgCl@PANI through
      coordination bonds instead of electrostatic interaction. The resulting AuNPs
      AgCl@PANI hybrid material exhibited good electroactivity at a neutral pH
      environment. An amperometric glucose biosensor was developed by adsorption of
      glucose oxidase (GOx) on an AuNPs-AgCl@PANI modified glassy carbon (GC)
      electrode. AuNPs-AgCl@PANI could provide a biocompatible surface for high enzyme
      loading. Due to size effect, the AuNPs in the hybrid material could act as a good
      catalyst for both oxidation and reduction of H(2)O(2). As the measurement of
      glucose was based on the electrochemical detection of H(2)O(2) generated by
      enzyme-catalyzed-oxidation of glucose, the biosensor exhibited a super highly
      sensitive response to the analyte with a detection limit of 4 pM. Moreover, the
      biosensor showed good reproducibility and operation stability. The effects of
      some factors, such as temperature and pH value, were also studied.

PMID- 18093822
TI  - Integration of light-controlled neuronal firing and fast circuit imaging.
AB  - For understanding normal and pathological circuit function, capitalizing on the
      full potential of recent advances in fast optical neural circuit control will
      depend crucially on fast, intact-circuit readout technology. First, millisecond
      scale optical control will be best leveraged with simultaneous millisecond-scale
      optical imaging. Second, both fast circuit control and imaging should be
      adaptable to intact-circuit preparations from normal and diseased subjects. Here
      we illustrate integration of fast optical circuit control and fast circuit
      imaging, review recent work demonstrating utility of applying fast imaging to
      quantifying activity flow in disease models, and discuss integration of diverse
      optogenetic and chemical genetic tools that have been developed to precisely
      control the activity of genetically specified neural populations. Together these
      neuroengineering advances raise the exciting prospect of determining the role
      specific cell types play in modulating neural activity flow in neuropsychiatric
      disease.

PMID- 18093823
TI  - Neuronal and glial cell biology.

PMID- 18093825
TI  - New technologies for neuroscience.

PMID- 18093824
TI  - MRI contrast agents for functional molecular imaging of brain activity.
AB  - Functional imaging with MRI contrast agents is an emerging experimental approach
      that can combine the specificity of cellular neural recording techniques with
      noninvasive whole-brain coverage. A variety of contrast agents sensitive to
      aspects of brain activity have recently been introduced. These include new probes
      for calcium and other metal ions that offer high sensitivity and membrane
      permeability, as well as imaging agents for high-resolution pH and metabolic
      mapping in living animals. Genetically encoded MRI contrast agents have also been
      described. Several of the new probes have been validated in the brain; in vivo
      use of other agents remains a challenge. This review outlines advantages and
      disadvantages of specific molecular imaging approaches and discusses current or
      potential applications in neurobiology.

PMID- 18093827
TI  - Expert opinion on management of gastric and gastro-oesophageal junction
      adenocarcinoma on behalf of the European Organisation for Research and Treatment
      of Cancer (EORTC)-gastrointestinal cancer group.
AB  - A multidisciplinary approach is mandatory for patients with gastric cancer.
      Patients should be managed by an experienced team of physicians. The outcome of
      patients is related to the experience of the multidisciplinary team. Surgery is
      the cornerstone of the management of patients with resectable gastric cancer. The
      standard recommendations for resectable gastric adenocarcinoma are free-margin
      surgery with at least D1 resection combined to removal of a minimum of 15 lymph
      nodes. It has been shown that the outcome of patients with resectable gastric
      cancer can be improved by a strategy of perioperative (pre- and postoperative)
      chemotherapy or by postoperative chemoradiotherapy. The evidence comes from large
      randomised phase 3 studies. In the treatment of unresectable, locally advanced or
      metastatic gastric or gastro-oesophageal junction adenocarcinoma, no chemotherapy
      combination was accepted as the gold standard. Cisplatin/5-FU (CF) and ECF
      (epirubicin plus CF) regimens have been investigated widely in clinical studies
      and were until recently presented as the reference regimens. Despite a relative
      chemosensitivity of gastric cancer, a low rate of complete response was obtained,
      the response duration was short and patients' outcomes remained poor. Recently,
      new options have been introduced in the management of advanced gastric cancer. It
      has been shown that capecitabine is at least as good as 5-FU and that oxaliplatin
      at least as good as cisplatin in these combinations. It has also been
      demonstrated that the addition of docetaxel to CF resulted in statistically
      significant improved efficacy endpoints (including patient's quality of life),
      but also in an increased toxicity. The DCF regimen (docetaxel, cisplatin and 5
      FU) has become, therefore, a new active option in advanced gastric cancer in
      selected patients in good condition. Further randomised trials are therefore to
      be designed to further improve chemotherapy by modifying and optimising the
      chemotherapy regimens, and investigating novel treatment combinations. The
      addition of biological agents to the optimal chemotherapy regimen may achieve
      further improvements in efficacy.

PMID- 18093828
TI  - Oncological safety and patient satisfaction with skin-sparing mastectomy and
      immediate breast reconstruction.
AB  - INTRODUCTION: The management of early breast cancer with skin-sparing mastectomy
      (SSM) and immediate breast reconstruction (IBR) is not based on evidence from
      randomised controlled trials. The purpose of this study is to evaluate the
      oncological safety, post-operative morbidity and patients' satisfaction with SSM
      and IBR using the latissimus dorsi (LD) myocutaneous flap and/or breast
      prosthesis. METHODS: Eighty-three consecutive women underwent 93 SSMs with IBR
      (10 bilateral), using the LD flap plus implant (n=55) or implant alone (n=38),
      indications included early breast cancer and prophylaxis due to BRCA-1 gene
      mutation. Nipple reconstruction was performed in 38 patients, using the trefoil
      local flap technique, nipple sharing or Monocryl mesh. Twenty-three underwent
      contra-lateral surgery in order to optimise symmetry, including 15 augmentations
      and eight mastopexy/reduction mammoplasties. Patient satisfaction with the
      outcome of surgery was assessed on a linear visual analogue scale ranging from 0
      (not satisfied) to 10 (most satisfied). RESULTS: There was no local recurrence
      (LR) after a median follow-up of 34 months (range=3-79 months). Overall survival
      was 98.8%, three patients developed distant disease and one patient died of
      metastatic breast cancer. No case of partial or total LD flap loss was observed.
      Morbidities included infection, requiring implant removal in two patients and one
      patient developed marginal ischaemia of the skin envelope. Significant capsule
      formation, requiring capsulotomy, was observed in 87% of patients who had either
      PMR or prior RT compared with 13% for those who did not have RT. Sixty-one
      (73.5%) of 83 patients completed the questionnaire with a median and mean
      satisfaction scores of 10.0 and 9.3, respectively (range=6-10). CONCLUSION: SSM
      with IBR is associated with low morbidity, high levels of patient satisfaction
      and is oncologically adequate for T(is), T1 and T2 tumours without extensive skin
      involvement.

PMID- 18093826
TI  - Techniques for extracting single-trial activity patterns from large-scale neural
      recordings.
AB  - Large, chronically implanted arrays of microelectrodes are an increasingly common
      tool for recording from primate cortex and can provide extracellular recordings
      from many (order of 100) neurons. While the desire for cortically based motor
      prostheses has helped drive their development, such arrays also offer great
      potential to advance basic neuroscience research. Here we discuss the utility of
      array recording for the study of neural dynamics. Neural activity often has
      dynamics beyond that driven directly by the stimulus. While governed by those
      dynamics, neural responses may nevertheless unfold differently for nominally
      identical trials, rendering many traditional analysis methods ineffective. We
      review recent studies - some employing simultaneous recording, some not -
      indicating that such variability is indeed present both during movement
      generation and during the preceding premotor computations. In such cases, large
      scale simultaneous recordings have the potential to provide an unprecedented view
      of neural dynamics at the level of single trials. However, this enterprise will
      depend not only on techniques for simultaneous recording but also on the use and
      further development of analysis techniques that can appropriately reduce the
      dimensionality of the data, and allow visualization of single-trial neural
      behavior.

PMID- 18093829
TI  - Adsorption kinetics of a basic dye from aqueous solutions onto apricot stone
      activated carbon.
AB  - The preparation of activated carbon from apricot stone with H(2)SO(4) activation
      and its ability to remove a basic dye, astrazon yellow 7 GL, from aqueous
      solutions were reported in this study. The adsorbent was characterized by FTIR,
      BET and SEM, respectively. The effects of various experimental parameters, such
      as initial dye concentration, pH, adsorbent dosage and temperature were
      investigated in a batch-adsorption technique. The optimum conditions for removal
      of the basic dye were found to be pH 10, 6g/l of adsorbent dosage and equilibrium
      time of 35 min, respectively. A comparison of three kinetic models, the pseudo
      first-order, second-order and diffusion controlled kinetic models, on the basic
      dye-adsorbent system showed that the removal rate was heavily dependent on
      diffusion controlled kinetic models. The adsorption isotherm data were fitted
      well to Langmuir and Freundlich isotherms. The adsorption capacity was calculated
      as 221.23 mg/g at 50 degrees C. Thermodynamics parameters were also evaluated.
      The values of enthalpy and entropy were 49.87 kJ/mol and 31.93 J/mol K,
      respectively, indicating that this process was spontaneous and endothermic. The
      experimental studies were indicated that ASC had the potential to act as an
      alternative adsorbent to remove the basic dye from aqueous solutions.

PMID- 18093830
TI  - Effect of temperatures and pH on methyl violet biosorption by Mansonia wood
      sawdust.
AB  - In this study, the effect of temperature on the equilibrium biosorption of methyl
      violet dye from aqueous solution using Mansonia wood sawdust was studied. The
      equilibrium biosorption data were analyzed using three widely applied isotherm
      models; Langmuir, Freundlich and Redlich-Peterson isotherm. The fit of three
      linear Langmuir isotherm forms, the Freundlich isotherm, and the Redlich-Peterson
      isotherm were determined using linear and the non-linear methods. Langmuir
      isotherm parameters obtained from the three Langmuir linear equations by using
      linear method were dissimilar, except, when the non-linear method was used. Best
      fits were yielded with Langmuir and Redlich-Peterson isotherms. The methyl violet
      biosorption was strongly dependent solution pH and percentage dye removal became
      significant above pH 7, which was slightly higher than the pH(PZC) of the sawdust
      material. In addition, various thermodynamic parameters, such as DeltaG degrees ,
      DeltaH degrees , and DeltaS degrees were calculated. Results suggested that the
      biosorption was a spontaneous and endothermic process.

PMID- 18093831
TI  - Pediocin SA-1, an antimicrobial peptide from Pediococcus acidilactici NRRL B5627:
      production conditions, purification and characterization.
AB  - Fermentation broths of Pediococcus acidilactici NRRL B5627 exhibited a certain
      antimicrobial activity due to a bacteriocin produced during early growth and
      until the stationary phase of growth was reached (at optimum of 60% dissolved
      oxygen saturation). Its size was determined by electrospray ionization mass
      spectrometric analysis as 3.660 kDa. N-terminal sequencing showed that the
      bacteriocin had 19 amino acid residues in the order KYYGXNGVXTXGKHSXVDX. The
      purified bacteriocin is similar to pediocins isolated by various Pediococci and
      therefore, it belongs to the class IIa of bacteriocins and is thus designated
      pediocin SA-1. Sensitivity of the purified pediocin to various storage
      temperatures and enzyme treatments was examined. Purified pediocin SA-1 is heat
      stable for up to 60 min at 121 degrees C. Pediocin SA-1 is inhibitory to several
      food-borne pathogens and food spoilage bacteria. It appears to be significantly
      more effective against Listeria spp. compared to pediocin PD-1 produced by P.
      damnosus. The mode of action of the purified bacteriocin appears to be
      bactericidal.

PMID- 18093832
TI  - Design and synthesis of macrocyclic peptidyl hydroxamates as peptide deformylase
      inhibitors.
AB  - Macrocyclic peptidyl hydroxamates were designed, synthesized, and evaluated as
      peptide deformylase (PDF) inhibitors. The most potent compound exhibited tight,
      slow-binding inhibition of Escherichia coli PDF (K(I)(*)=4.4 nM) and had potent
      antibacterial activity against Gram-positive bacterium Bacillus subtilis (MIC=2-4
      microg/mL).

PMID- 18093833
TI  - Toe clearance variability during walking in young and elderly men.
AB  - Falls during walking are a major cause of injury and death in the elderly. From a
      falls perspective, a critical gait event is minimum toe clearance (MTC), as
      failure to achieve foot-ground clearance results in a trip and potentially a
      fall. MTC exhibits stride-to-stride variability, which must be minimised to avoid
      the occurrence of toe-ground contact events. Gait kinematics were acquired from
      10 young and nine elderly men for 1000 sequential strides during treadmill
      walking. The swing toe was modelled as the endpoint of a 21 degree-of-freedom
      kinematic chain. Central tendency and dispersion of MTC, stance foot angles and
      stance and swing leg joint angles at the time of MTC (time(MTC)) were compared
      between the young and elderly. The relationship between joint angle variability
      and MTC variability was also examined in both age groups. No age-related
      differences in median MTC were identified, however within-subject variability of
      MTC was greater for the elderly than the young. The elderly also displayed less
      stance hip extension, greater swing hip flexion and less stance hip adduction at
      time(MTC) than the young. No age-related differences in stance foot or joint
      angle variability were identified. MTC variability was most strongly correlated
      with swing ankle plantar-dorsiflexion variability for the young group and stance
      ankle adduction-abduction variability for the elderly. In conclusion, elderly men
      exhibit greater MTC variability than young men, which in the absence of an age
      related increase in median MTC, may increase the risk of tripping in the elderly.

PMID- 18093834
TI  - Predicting lower limb joint kinematics using wearable motion sensors.
AB  - The aim of this study was to estimate sagittal plane ankle, knee and hip gait
      kinematics using 3D angular velocity and linear acceleration data from motion
      sensors on the foot and shank. We explored the accuracy of intra-subject
      predictions (i.e., where training and testing uses trials from the same subject)
      and inter-subject (where testing uses subjects different from the ones used for
      training) predictions, and the effect of loss of sensor data on prediction
      accuracy. Hip, knee and ankle kinematic data were collected using reflective
      markers. Simultaneously, foot and shank angular velocity and linear acceleration
      data were collected using small integrated accelerometers/gyroscope units. A
      generalised regression networks algorithm was used to predict the former from the
      latter. The best results were from intra-subject predictions, with very high
      correlations (0.93-0.99) and low mean absolute deviation (< or =2.3 degrees )
      between measured kinematic joint angles and predicted angles. The inter-subject
      case produced poorer correlations (0.70-0.89) and larger absolute differences
      between measured and predicted angles, ranging from 4.91 degrees (left ankle) to
      9.06 degrees (right hip). The angular velocity data added little to the accuracy
      of predictions and there was also minimal benefit to using sensor data from the
      shank. Thus, a wearable system based only on footwear mounted sensors and a
      simpler sensor set providing only acceleration data shows potential. Whilst
      predictions were generally stable when sensor data was lost, it remains to be
      seen whether the generalised regression networks algorithm is robust for other
      activities such as stair climbing.

PMID- 18093835
TI  - Synthesis and antiproliferative activity of benzyl and phenethyl analogs of
      makaluvamines.
AB  - Analogs of marine alkaloid, makaluvamine, bearing substituted benzyl and
      substituted phenethyl side chains have been synthesized and their
      antiproliferative activities have been evaluated. 4-Methyl, 4-chloro, and 4
      fluoro substituted benzyl analogs possessed pronounced antiproliferative effects
      on the breast cancer cell line, MCF-7 at IC(50) values of 2.3 microM, 1.8 microM,
      and 2.8 microM, respectively. 4-Methyl, 4-chloro, and 3,4-methylenedioxy
      derivatives showed the best activity against MCF-7 among the phenethyl analogs
      with IC(50) values of 2.3 microM, 2.8 microM, and 2.4muM, respectively. In
      general, methoxy substitutions resulted in slight loss in activity in both benzyl
      and phenethyl series. Benzyl, 4-fluorobenzyl, 3,4-dimethoxyphenethyl, and 3,4
      methylenedioxyphenethyl analogs were tested by NCI in their 60 cell lines in
      vitro human cancer cell screen. All four compounds showed excellent inhibition
      against several tested cancer cell lines. Benzyl and 4-fluorobenzyl analogs were
      relatively more active than 3,4-dimethoxy phenethyl and 3,4-methylenedioxy
      phenethyl analogs. In NCI assays, the best LogGI(50) values were shown by the
      fluorobenzyl analog against the renal cancer cell line RXF-393 (<-8.0M) and
      dimethoxy phenethyl analog against the CNS cancer cell line, SF-268 (<-8.0M). The
      best LogLC(50) value was shown by the fluorobenzyl analog against the breast
      cancer cell line MCF-7 (-6.01 M).

PMID- 18093836
TI  - Intracardiac lipid accumulation, lipoatrophy of muscle cells and expansion of
      myocardial infarction in type 2 diabetic patients.
AB  - The overall mortality of diabetic patients after myocardial infarction is 3-4
      times higher than non-diabetics. The cellular mechanisms underlying such a poor
      clinical prognosis remain incompletely understood. Recent reports suggest that
      lipotoxicity associated with impaired liporegulation is among the leading factors
      in the pathogenesis of type 2 diabetes. The goal of this study was to investigate
      whether excess lipid accumulation specifically in heart muscle cells contributes
      to the expansion of myocardial infarction in type 2 diabetic patients.
      Comparative structural analysis of cardiac tissue was performed on autopsy
      samples from the infracted hearts of diabetic and non-diabetic individuals with
      special reference to the expansion of the infarction, degenerative changes,
      lipoatrophy, cell death, and replacement fibrosis. We found that progressive
      accumulation of lipids in cardiac myocytes was accompanied by considerable loss
      of myofibrils and was frequently observed in the heart tissue of type 2 diabetic
      patients. This indicates that disassembly of the contractile apparatus in the
      cells infiltrated with lipids weakens their capability for functional activity.
      Analysis of degenerative changes in the diabetic tissue has shown that lipid
      laden cardiac myocytes were more susceptible to necrotic and apoptotic cells
      death leading to expansion of the infarction and the development of progressive
      focal replacement fibrosis both in the perinecrotic zone and in the areas located
      far from the site of injury. Our data show that lipoatrophy and loss of muscle
      cells during the post-infarction period aggravate the functional impairment in
      the diabetic heart and limits its adaptive capacity for compensatory remodeling.
      This suggests that lipotoxic myocardial injury associated with defects of lipid
      metabolism in type 2 diabetes predisposes its evolution toward congestive heart
      failure and is an important factor contributing to a high mortality following
      infarction.

PMID- 18093837
TI  - Radiolabeling procedure, quality control and stability of 99mTc-labeled
      chondroitin sulfate: a new approach of targeting osteoarthritis.
AB  - Chondroitin sulfate (CS) is an endogenous component of cartilage which could
      determine osteoarthritis after radiolabeling. Radiolabeling was performed by
      (99m)TcO(4)(-)/tin method. We found that pH is a limiting factor. At pH 6.2 in
      0.05 M Na acetate buffer 32.8% colloid was formed, at pH 5.0 in 0.5M Na acetate,
      in our methodology only 4.7% colloid. The tracer was highly stable. We conclude
      that (99m)TcCS could be a promising imaging agent of osteoarthritis due to simple
      radiolabeling and high stability.

PMID- 18093838
TI  - Pseudo-myxoma: massive pulmonary vein metastasis from a primary breast carcinoma.

PMID- 18093839
TI  - Bactericidal effect of photodynamic inactivation against methicillin-resistant
      and methicillin-susceptible Staphylococcus aureus is strain-dependent.
AB  - Staphylococcus aureus is one of the most important etiological factors
      responsible for nosocomial infections. Some of them may be life-threatening,
      especially in the case of immuno-compromised patients, causing bacteremia,
      endocarditis, sepsis or toxic-shock syndrome. Their multiresistance to
      antibiotics produces many therapeutic problems, and for this reason the
      development of a method alternative to antibiotic therapy is needed. It seems
      that photodynamic inactivation (PDI) may be an effective and alternative
      therapeutic option against both methicillin resistant (MRSA) and methicillin
      sensitive (MSSA) S. aureus strains. The aim of this study was to analyze the
      bactericidal effect of the PDI against 40 clinical MRSA and 40 MSSA clinical
      strains that were isolated from patients hospitalized in the Provincial Hospital
      in Gdansk. The ATCC strain 25904 has been used as a reference. Photodynamic
      inactivation by means of protoporphyrin diarginate as a photosensitizer was
      examined. It was observed that the bactericidal effect of the PDI was strain
      dependent and ranged from 0 to 3 log(10)-unit reduction in viable counts. The
      mechanism underlying such a phenomenon is still not understood. Nevertheless, the
      correlation between the biofilm production ability and different strains response
      to PDI has been observed.

PMID- 18093840
TI  - TPO-independent megakaryocytopoiesis.
AB  - Megakaryocytopoiesis is a continuous developmental process of platelet
      production. In this process, a complex network of hemopoietic growth factors are
      involved, among which TPO (thrombopoietin) is the most thoroughly investigated
      regulator of MKs (megakaryocytes). In addition to TPO, other regulators also have
      non-negligible effects on megakaryocytopoiesis. The majority of their effects are
      independent of TPO signaling. To date, TPO-independent megakaryocytopoiesis forms
      a regulatory system that includes four signals and (an) unknown signaling
      pathway(s). These four pathways are the gp 130 (glycoprotein 130)-dependent
      signaling pathway, the Notch pathway, NMDA (N-methyl-d-aspartate) receptor
      mediated signaling, and the SDF-1 (stromal cell-derived factor-1)/FGF-4
      (fibroblast growth factor-4) paradigm. Understanding of the TPO-independent
      regulatory system is important because the system may offer additional
      opportunities to understand the developmental process and the mechanisms of
      disorders characterized by abnormal MK and platelet production, such as
      thrombocytopenia and thrombocythemia, and to advance the development of
      therapeutics.

PMID- 18093842
TI  - Electromyographic analysis of pedaling: a review.
AB  - Although pedaling is constrained by the circular trajectory of the pedals, it is
      not a simple movement. This review attempts to provide an overview of the
      pedaling technique using an electromyographic (EMG) approach. Literature
      concerning the electromyographic analysis of pedaling is reviewed in an effort to
      make a synthesis of the available information, and to point out its relevance for
      researchers, clinicians and/or cycling/triathlon trainers. The first part of the
      review depicts methodological aspects of the EMG signal recording and processing.
      We show how the pattern of muscle activation during pedaling can be analyzed in
      terms of muscle activity level and muscle activation timing. Muscle activity
      level is generally quantified with root mean square or integrated EMG values.
      Muscle activation timing is studied by defining EMG signal onset and offset times
      that identify the duration of EMG bursts and, more recently, by the determination
      of a lag time maximizing the cross-correlation coefficient. In the second part of
      the review, we describe whether the patterns of the lower limb muscles activity
      are influenced by numerous factors affecting pedaling such as power output,
      pedaling rate, body position, shoe-pedal interface, training status and fatigue.
      Some research perspectives linked to pedaling performance are discussed
      throughout the manuscript and in the conclusion.

PMID- 18093841
TI  - Total stenosis triggers compensatory responsiveness of carotid and basilar
      arteries to endothelin-1 and phenylephrine.
AB  - The aim of this study was to investigate whether total stenosis of the common
      carotid artery (ipsilateral) would affect the vascular responsiveness of the
      contralateral carotid as well as the basilar artery from guinea pigs. With this
      purpose, the carotid artery was occluded with a silk thread at a position close
      to its origin. Vascular reactivity experiments using standard muscle bath were
      performed 7, 15, 30, and 90 days after carotid occlusion. Stenosis induced a
      progressive reduction in the contraction induced by endothelin-1, phenylephrine
      and KCl in the ipsilateral carotid, when compared to their respective age-matched
      SHAM groups. Endothelial removal or incubation of endothelium-intact ipsilateral
      carotids with L-NAME, a nitric oxide synthase inhibitor, did not alter the
      response to endothelin-1 or phenylephrine, when compared to the endothelium
      intact ipsilateral carotid in the absence of the inhibitor. Interestingly, an
      increased contractile response to endothelin-1, phenylephrine and KCl was
      observed in the contralateral carotid. Indomethacin, a non-selective
      cyclooxygenase inhibitor, prevented the increased contraction to endothelin-1 in
      the contralateral carotid. Stenosis also induced an increase in the contractile
      response to endothelin-1 in the basilar artery while the contractile response to
      phenylephrine and KCl were reduced. Indomethacin, but not L-NAME, prevented the
      increased contraction to endothelin-1 in the basilar artery. Morphometric
      analysis showed no differences in the medial area (wall thickness) of carotid or
      basilar arteries from the stenosis group when compared to their respective age
      matched SHAM groups. The present study confirms the importance of adaptation to
      stenosis on the vascular reactivity of the stenosed artery to different
      vasoconstrictor agents. Moreover, our results show that stenosis induces
      alterations of the vascular reactivity on arteries distant from the site of
      injury. The increased response to endothelin-1 in the contralateral carotid
      artery and basilar artery seems to involve the release of vasoconstrictor
      prostanoids from endothelial origin.

PMID- 18093843
TI  - Agonist muscle activity and antagonist muscle co-activity levels during
      standardized isotonic and isokinetic knee extensions.
AB  - This study aimed to analyze the effects of the contraction mode (isotonic vs.
      isokinetic concentric conditions), the joint angle and the investigated muscle on
      agonist muscle activity and antagonist muscle co-activity during standardized
      knee extensions. Twelve healthy adult subjects performed three sets of isotonic
      knee extensions at 40% of their maximal voluntary isometric torque followed by
      three sets of maximal isokinetic knee extensions on an isokinetic dynamometer.
      For each set, the mean angular velocity and the total external amount of work
      performed were standardized during the two contraction modes. Surface
      electromyographic activity of vastus lateralis (VL), vastus medialis (VM), rectus
      femoris (RF), semitendinosus (ST) and biceps femoris (BF) muscles was recorded.
      Root mean square values were then calculated for each 10 degrees between 85
      degrees and 45 degrees of knee extension (0 degrees =horizontal position).
      Results show that agonist muscle activity and antagonist muscle co-activity
      levels are significantly greater in isotonic mode compared to isokinetic mode.
      Quadriceps activity and hamstrings co-activity are significantly lower at knee
      extended position in both contraction modes. Considering agonist muscles, VL
      reveals a specific pattern of activity compared to VM and RF; whereas considering
      hamstring muscles, BF shows a significantly higher co-activity than ST in both
      contraction modes. Results of this study confirmed our hypothesis that higher
      quadriceps activity is required during isotonic movements compared to isokinetic
      movements leading to a higher hamstrings co-activity.

PMID- 18093845
TI  - Neural correlates of the processing of co-speech gestures.
AB  - In communicative situations, speech is often accompanied by gestures. For
      example, speakers tend to illustrate certain contents of speech by means of
      iconic gestures which are hand movements that bear a formal relationship to the
      contents of speech. The meaning of an iconic gesture is determined both by its
      form as well as the speech context in which it is performed. Thus, gesture and
      speech interact in comprehension. Using fMRI, the present study investigated what
      brain areas are involved in this interaction process. Participants watched videos
      in which sentences containing an ambiguous word (e.g. She touched the mouse) were
      accompanied by either a meaningless grooming movement, a gesture supporting the
      more frequent dominant meaning (e.g. animal) or a gesture supporting the less
      frequent subordinate meaning (e.g. computer device). We hypothesized that brain
      areas involved in the interaction of gesture and speech would show greater
      activation to gesture-supported sentences as compared to sentences accompanied by
      a meaningless grooming movement. The main results are that when contrasted with
      grooming, both types of gestures (dominant and subordinate) activated an array of
      brain regions consisting of the left posterior superior temporal sulcus (STS),
      the inferior parietal lobule bilaterally and the ventral precentral sulcus
      bilaterally. Given the crucial role of the STS in audiovisual integration
      processes, this activation might reflect the interaction between the meaning of
      gesture and the ambiguous sentence. The activations in inferior frontal and
      inferior parietal regions may reflect a mechanism of determining the goal of co
      speech hand movements through an observation-execution matching process.

PMID- 18093844
TI  - Kinetic analysis in healthy humans of a novel positron emission tomography
      radioligand to image the peripheral benzodiazepine receptor, a potential
      biomarker for inflammation.
AB  - The peripheral benzodiazepine receptor (PBR) is upregulated on activated
      microglia and macrophages and thereby is a useful biomarker of inflammation. We
      developed a novel PET radioligand, [(11)C]PBR28, that was able to image and
      quantify PBRs in healthy monkeys and in a rat model of stroke. The objective of
      this study was to evaluate the ability of [(11)C]PBR28 to quantify PBRs in brain
      of healthy human subjects. Twelve subjects had PET scans of 120 to 180 min
      duration as well as serial sampling of arterial plasma to measure the
      concentration of unchanged parent radioligand. One- and two-tissue compartmental
      analyses were performed. To obtain stable estimates of distribution volume, which
      is a summation of B(max)/K(D) and nondisplaceable activity, 90 min of brain
      imaging was required. Distribution volumes in human were only approximately 5% of
      those in monkey. This comparatively low amount of receptor binding required a two
      rather than a one-compartment model, suggesting that nonspecific binding was a
      sizeable percentage compared to specific binding. The time-activity curves in two
      of the twelve subjects appeared as if they had no PBR binding-i.e., rapid peak of
      uptake and fast washout from brain. The cause(s) of these unusual findings are
      unknown, but both subjects were also found to lack binding to PBRs in peripheral
      organs such as lung and kidney. In conclusion, with the exception of those
      subjects who appeared to have no PBR binding, [(11)C]PBR28 is a promising ligand
      to quantify PBRs and localize inflammation associated with increased densities of
      PBRs.

PMID- 18093846
TI  - Phylogeography across a continent: the evolutionary and demographic history of
      the North American racer (Serpentes: Colubridae: Coluber constrictor).
AB  - Most phylogeographic studies examine organisms that do not have transcontinental
      distributions and therefore the genetic and temporal effects of barriers across
      an entire continent cannot be assessed with respect to a single species. We
      examined the phylogeographic structure, lineage age, and historical demography
      using sequences from the mtDNA cytochrome b gene of the widespread North American
      racer (Coluber constrictor), one of the few abundant transcontinental snakes that
      occurs throughout many diverse biomes. Our results indicate that this complex is
      comprised of six lineages differing greatly in geographic extent, with the
      largest (a central US clade) being approximately 26 times greater than the
      smallest (a lineage restricted to the Florida Panhandle and nearby portions of
      adjacent States). Most of the six lineages appear to be separated at previously
      identified genetic barriers for several vertebrates with similar ranges. Lineage
      diversification in this species began in the late Miocene, separating populations
      in the Florida Peninsula from the remainder of the US. Diversification of
      lineages continued throughout the Pliocene and early Pleistocene. Four of the six
      lineages occur east of the Mississippi River, with only two distinctly young (
      approximately 1.5 mya) lineages found west of the Mississippi River (one occurs
      west of Continental Divide). All methods of demographic inference, including the
      mismatch distribution, Fu and Li's D and Tajima's D , and Bayesian skyline plots
      revealed population expansion occurring in the mid-to-late Pleistocene for every
      lineage, regardless of size or proximity to formerly glaciated areas. Population
      expansion for lineages found east of the Mississippi River occurred earlier and
      was much greater than those found west of the River.

PMID- 18093847
TI  - Meniscal tear and increased tibial plateau bone area in healthy post-menopausal
      women.
AB  - OBJECTIVE: Meniscal tears detected using magnetic resonance imaging (MRI) have
      been identified as a risk factor for the development and progression of
      Osteoarthritis, however the prevalence and significance of meniscal tears in
      healthy, asymptomatic adults remains to be studied. We investigated the
      prevalence of meniscal tears in a healthy pain free population of post-menopausal
      women and whether meniscal tears in this population are associated with changes
      in cartilage volume and defects and tibial plateau bone area over 2 years.
      METHODS: Fifty-seven post-menopausal women underwent MRI of their dominant knee
      at baseline line and approximately 2 years later to assess meniscal tears,
      cartilage volume, cartilage defects and tibial plateau bone area. RESULTS: Forty
      six percent of women had a meniscal tear in either the medial and/or lateral
      compartment. Women who had a tear were older (P=0.01) and had more lateral
      cartilage defects (P=0.02). Medial meniscal tear was associated with 103 mm(2)
      greater tibial plateau bone area within the medial [95% confidence of interval
      (CI) 6.2, 200.3; P=0.04] and a lateral meniscal tear with a 120 mm(2) greater
      area within the lateral compartment (95% CI 45.5, 195.2; P=0.002). CONCLUSION:
      This study demonstrates that meniscal tears are common in asymptomatic post
      menopausal women and that they become more common with age. Meniscal tears were
      also associated with greater tibial plateau bone area but not cartilage volume,
      providing support to the hypothesis that tibial plateau bone changes occur before
      significant pathological changes in cartilage. Whether increased tibial plateau
      bone area predisposes to an increased risk of degenerative meniscal tears or
      whether it is a consequence of altered biomechanical forces in relation to
      meniscal tear will need to be determined.

PMID- 18093849
TI  - Oligomycin A and the IPLB-LdFB insect cell line: actin and mitochondrial
      responses.
AB  - Oligomycin A, an inhibitor of mitochondrial ATP synthase, provokes simultaneous
      and different responses in IPLB-LdFB insect cell line. The oligomycin A treatment
      causes mitochondrial loss, increase in reactive oxygen species (ROS),
      destabilization/reorganization of the actin microfilaments and, finally,
      autophagic cell death. We speculate that oligomycin A affects the mitochondria
      and that the impairment of these organelles leads to the generation of ROS in
      quantities that exceed the antioxidant capacity of the cell. This in turn would
      lead to a feedback loop of increased mitochondrial impairment, amplification of
      ROS production and the removal of damaged organelles through autophagy.

PMID- 18093848
TI  - Aqueous extract of the Chinese medicine, Danggui-Shaoyao-San, inhibits apoptosis
      in hydrogen peroxide-induced PC12 cells by preventing cytochrome c release and
      inactivating of caspase cascade.
AB  - Danggui-Shaoyao-San (DSS), a traditional Chinese medicine used for centuries for
      the enhancement of women's health, has been shown to display therapeutic efficacy
      on senile dementia. In the present study, using a rat pheochromocytoma (PC12)
      cell line, the effect of DSS on hydrogen peroxide (H2O2) induced apoptosis was
      studied. The apoptosis in H2O2-induced PC12 cells was accompanied by
      downregulation of Bcl-2, upregulation of Bax, the release of mitochondrial
      cytochrome c into cytosol, and sequential activation of caspase-9 and -3. DSS was
      able to suppress all these changes and eventually protected against H2O2-induced
      apoptosis. Taken together, these results suggest that treatment of PC12 cells
      with DSS can block H2O2-induced apoptosis by the regulation of Bcl-2 family
      members, as well as suppression of cytochrome c release and caspase cascade
      activation.

PMID- 18093850
TI  - Adenovirus-mediated RNA interference against collagen-specific molecular
      chaperone 47-KDa heat shock protein suppresses scar formation on mouse wounds.
AB  - It has been shown in many investigations that the abnormally increasing
      production and deposition of collagen is one of the important mechanisms of
      pathological scars and other fibrotic diseases [Wang Z, Inokuchi T, Nemoto TK,
      Uehara M, Baba TT. Antisense oligonucleotide against collagen-specific molecular
      chaperone 47-kDa heat shock protein suppresses scar formation in rat wounds.
      Plast Reconstr Surg 2003 May; 111(6):1980-7; Obayashi K, Akamatsu H, Okano Y,
      Matsunage K, Masaki H. Exogenous nitric oxide enhances the synthesis of type I
      collagen and heat shock protein 47 by normal human dermal fibroblasts. J Dermatol
      Sci 2006 Feb; 41(2): 121-6 [e pub. 2005 Sep 19]; Kakugawa T, Mukae H, Hayashi T,
      Ishii H, Nakayama S, Sakamoto N, et-al. Expression of HSP47 in usual interstitial
      pneumonia and nonspecific interstitial pneumonia. Respir Res 2005 Jun;14(6): 57;
      Razzaque MS, Taguchi T. The possible role of colligin/HSP47, a collagen-binding
      protein, in the pathogenesis of human and experimental fibrotic diseases. Histol
      Histopathol 1999 Oct; 14(4): 1199-1212; Sharp PA. RNA interference - 2001. Genes
      Dev 2001 Mar 1; 15(5): 485-90; Ohashi S, Abe H, Takahashi T, Yamamoto Y, Takeuchi
      M, Arai H, et-al. Advanced glycation end products increase collagen-specific
      chaperone protein in mouse diabetic nephropathy. J Biol Chem 2004 May 7; 279(19):
      19816-23 [epub 2004 Mar 5]]. RNA interference is the process that double-stranded
      RNA induces the homology-dependent degradation of cognate mRNA mediated by 21-23
      nucleotide short interfering RNA (siRNA). In this study, we investigated the
      effect of HSP47-specific siRNA on the fibroblast cells, and then constructed
      adenovirus containing siRNA against HSP47 to inhibit the formation of scar in
      animal model. In this pilot study, HSP47 was targeted by this vector. Our results
      showed that the HSP47-specific siRNA could inhibit the expression of HSP47 at the
      level of mRNA and protein. Furthermore, adenovirus-mediated transfer of siRNA
      against HSP47 could inhibit the expression of type I collagen and the formation
      of scar tissue in animal model. It is likely that the inhibition of HSP47 by RNA
      interference (RNAi) could be developed as a powerful approach to prevent the scar
      formation.

PMID- 18093851
TI  - Role of p38 in regulation of hematopoiesis: effect of p38 inhibition on cytokine
      production and transcription factor activity in human bone marrow stromal cells.
AB  - This study was designed to evaluate effects of specific p38 MAP kinase inhibition
      on gene and protein expression of essential hematopoietic cytokines in primary
      human bone marrow stromal cells (HBMSC) and to identify downstream transcription
      factors (TF) regulated by the p38 MAP kinase signalling pathway. In vitro effects
      of p38 inhibitors (p38i) on cytokine regulation were compared to inhibitors of
      other major signalling pathways including PI3 kinase, JNK, MEK-1, NF-kappaB or
      protein kinase C (PKC). HBMSC were pre-treated with p38i (SB-203580) for 1 h and
      then stimulated with 200 ng/ml lipopolysaccharide (LPS). Supernatants and RNA
      were collected 6 h post LPS treatment for quantitative protein and mRNA analyses
      by ELISA and real-time RT-PCR, respectively, for interleukin-6 (IL-6),
      interleukin-11 (IL-11), granulocyte-monocyte colony-stimulating factor (GM-CSF),
      granulocyte colony-stimulating factor (G-CSF) and Activin A. Effects of the
      inhibitors of PI3 kinase (LY294002), JNK (synthetic inhibitory peptide), MEK-1
      (PD90859), NF-kappaB (pyrrolidinedithiocarbamate (PDTC)) and protein kinase C
      (calphostin C) on HBMSC expression hematopoietic cytokines were evaluated and
      compared. SB-203580 caused dose-dependent decreases in cytokine protein
      expression and decreased IL-6 and IL-11 mRNA expression. Of the pathway
      inhibitors examined, only NF-kappaB elicited similar effects on cytokine protein
      and mRNA expression. p38-regulated transcription factor activity was assessed
      using a DNA/Protein array. Several TFs linked to cytokine regulation were
      modulated by SB-203580, with 10 of 21 p38-regulated TFs identified have not been
      previously linked to downstream p38 signalling. These observations in cultured
      HBMSC have illustrated the involvement of cytokine proteins, mRNA and TF
      activities and may improve the current understanding of the in vivo p38i
      suppression of erythropoiesis. In addition, these results suggest that IL-6, IL
      11, GM-CSF, G-CSF and Activin A are similarly regulated by p38 and NF-kappaB and
      that the MEK1, JNK and PKC pathways appear to play a more limited role in
      modulating cytokine expression in HBMSC.

PMID- 18093852
TI  - Hydrophobins Sc3 and Sc4 gene expression in mounds, fruiting bodies and
      vegetative hyphae of Schizophyllum commune.
AB  - An abnormal growth form called mound has been hypothesized to be a neoplasm in
      the filamentous fungus Schizophyllum commune. An alternative hypothesis is that
      mounds represent some unusual developmental form in the fruiting body
      morphogenetic pathway. Hydrophobin proteins have been found in fruiting bodies
      where they line the surface of gas exchange pores and function to keep the pores
      hydrophobic. To further determine possible relationships between mounds and
      fruiting bodies, mound tissue was examined for gas exchange pores and the
      presence of hydrophobins. Cryoscanning electron microscopic images revealed the
      presence of channels in mound tissue and presumptive hydrophobin rodlets similar
      to the air channels in fruiting bodies. Hydrophobin gene expression was also
      measured in mound tissue using quantitative real-time PCR and showed both
      monokaryotic and dikaryotic mound tissue exhibited high expression of the
      dikaryotic specific Sc4 hydrophobin gene. In contrast, Sc4 hydrophobin expression
      was barely detectable in monokaryotic fruiting bodies. The expression of Sc4
      hydrophobin genes in mounds suggests mound development uses this aspect of the
      dikaryotic fruiting developmental pathway.

PMID- 18093853
TI  - Whole-bone mechanics: 'the best is the enemy of the good'.

PMID- 18093854
TI  - ENDOR evidence for the quantum exchange of the methylene protons.
AB  - ENDOR spectroscopy was used for studying methylene proton couplings in the 6-yl
      (or H-addition) radical in a single crystal of 1-methyluracil at 4.2K. The two
      methylene protons were magnetically equivalent in all crystal (radical)
      orientations in the magnetic field, indicating proton quantum exchange. The two
      protons compose magnetically single entity with spin I=1. The observed small
      ENDOR line splittings of about 0.60MHz agree well with the theoretical
      expectations for such a system.

PMID- 18093855
TI  - Continuity conditions and torsion angles from ssNMR orientational restraints.
AB  - The backbone torsion angle pair (varphi,psi) at each amino acid of a polypeptide
      is a descriptor of its conformation. One can use chemical shift and dipolar
      coupling data from solid-state NMR PISEMA experiments to directly calculate the
      torsion angles for the membrane-spanning portion of a protein. However,
      degeneracies inherent in the data give rise to multiple potential torsion angles
      between two adjacent peptide planes (a diplane). The molecular backbone structure
      can be determined by gluing together the consecutive diplanes, as in the PIPATH
      algorithm [T. Asbury, J.R. Quine, S. Achuthan, J. Hu, M.S. Chapman, T.A. Cross,
      R. Bertram, PIPATH: an optimized alogrithm for generating alpha-helical
      structures from PISEMA data, J. Magn. Reson. 183 (2006) 87-95.]. The
      multiplicities in torsion angles translate to multiplicities in diplane
      orientations. In this paper, we show that adjacent diplanes can be glued together
      to form a permissible structure only if they satisfy continuity conditions,
      described quantitatively here. These restrict the number of potential torsion
      angle pairs. We rewrite the torsion angle formulas from [J.R. Quine, M.T.
      Brenneman, T.A. Cross, Protein structural analysis from solid-state NMR-drived
      orientational constraints, Biophys. J. 72 (1997) 2342-2348.] so that they
      automatically satisfy the continuity conditions. The reformulated torsion angle
      formulas have been applied recently in the PIPATH algorithm [T. Asbury, J.R.
      Quine, S. Achuthan, J. Hu, M.S. Chapman, T.A. Cross, R. Bertram, PIPATH: an
      optimized alogrithm for generating alpha-helical structures from PISEMA data, J.
      Magn. Reson. 183 (2006) 87-95.] and will be helpful in other applications in
      which diplane gluing is used to construct a protein backbone model.

PMID- 18093856
TI  - Genome-scale analysis of anti-metabolite directed strain engineering.
AB  - Classic strain engineering methods have previously been limited by the low
      throughput of conventional sequencing technology. Here, we applied a new genomics
      technology, scalar analysis of library enrichments (SCALEs), to measure >3
      million Escherichia coli genomic library clone enrichment patterns resulting from
      growth selections employing three aspartic-acid anti-metabolites. Our objective
      was to assess the extent to which access to genome-scale enrichment patterns
      would provide strain-engineering insights not reasonably accessible through the
      use of conventional sequencing. We determined that the SCALEs method identified a
      surprisingly large range of anti-metabolite tolerance regions (423, 865, or 909
      regions for each of the three anti-metabolites) when compared to the number of
      regions (1-3 regions) indicated by conventional sequencing. Genome-scale methods
      uniquely enable the calculation of clone fitness values by providing
      concentration data for all clones within a genomic library before and after a
      period of selection. We observed that clone fitness values differ substantially
      from clone concentration values and that this is due to differences in overall
      clone fitness distributions for each selection. Finally, we show that many of the
      clones of highest fitness overlapped across all selections, suggesting that
      inhibition of aspartate metabolism, as opposed to specific inhibited enzymes,
      dominated each selection. Our follow up studies confirmed our observed growth
      phenotypes and showed that intracellular amino-acid levels were also altered in
      several of the identified clones. These results demonstrate that genome-scale
      methods, such as SCALEs, can be used to dramatically improve understanding of
      classic strain engineering approaches.

PMID- 18093857
TI  - Risk assessment of acute vascular events in congenital disorder of glycosylation
      type Ia.
AB  - The congenital disorder of glycosylation type Ia (CDG-Ia) presents a broad
      clinical spectrum. Some patients suffer from acute vascular events (thrombosis
      and bleeding) and stroke-like events. No correlations have been made between the
      marked hemostasis abnormalities of CDG-Ia and the occurrence of acute vascular
      events. We report on 6 patients with CDG-Ia presenting vascular events, then we
      analyze the clinical and hemostasis data of 39 CDG-Ia patients described in the
      literature, 17 with vascular events (E) and 21 unscathed from any event (EF), to
      determine the risk factors for acute vascular events in CDG-Ia. Acute vascular
      events occurred in patients younger than 15 years, especially with fever and
      prolonged immobilization. Hemostasis and liver cytolysis were statistically
      abnormal in patients younger than 5 years whatever the occurrence of vascular
      events and they normalized with time. Higher factors VIII and IX activities were
      statistically observed in the E cluster (p=0.03) compared to the EF cluster. The
      activity/antigenicity ratio for protein C (p=0.02) was also higher in the E
      group. CDG-Ia patients younger than 15 years old are at risk of acute vascular
      events. The paradoxical results-abnormal VIII and IX factors in EF patients and
      normal results in E patients, while XI, antithrombin, protein C, ASAT and ALAT
      are abnormal in both groups, could suggest a disequilibrium between prothrombotic
      and antithrombotic factors in the E group. Vascular events may also occur in
      patients where glycoproteins are proportionally more hypoglycosylated,
      particularly protein C.

PMID- 18093858
TI  - Increase in congenital hypothyroidism due to inadequate iodine nutrition?

PMID- 18093859
TI  - Recent trends in chlamydial and gonococcal conjunctivitis among neonates and
      adults in an Irish hospital.
AB  - BACKGROUND: Chlamydia trachomatis and Neisseria gonorrhoeae are two important and
      frequently overlooked causes of neonatal and adult conjunctivitis. OBJECTIVES AND
      METHODS: In order to improve primary treatment, prevention, and control of
      infection caused by these organisms, an analysis of all cases presenting from
      July 2002 to December 2006 at a major Irish regional teaching hospital was
      performed. RESULTS: There were 51 cases of conjunctivitis in total. Among
      neonates and adults, C. trachomatis was the most common cause of conjunctivitis.
      Of the adult patients, 75% were men. The annual incidence of adult chlamydial
      conjunctivitis increased yearly from 2002 and correlated with an overall increase
      in genital chlamydia infection in the region. Neonatal chlamydial conjunctivitis
      has an overall incidence of 0.65/1000 live births and is continuing to rise
      annually. In 2006, gonococcal conjunctivitis accounted for 20% of all cases of
      conjunctivitis caused by sexually transmitted bacteria presenting to our
      hospital. CONCLUSIONS: The recent increase in the incidence of gonococcal
      keratitis serves to remind us that this important infection should be borne in
      mind when treating cases of purulent conjunctivitis. The diagnosis of chlamydial
      and gonococcal conjunctivitis requires a high index of suspicion and prompt
      treatment with systemic antibiotics.

PMID- 18093861
TI  - Adipokines: the missing link between insulin resistance and obesity.
AB  - White adipose tissue was believed to be just an energy-storage organ, but it is
      now recognized to be an active participant in energy homoeostasis and
      physiological functions such as immunity and inflammation. Macrophages are
      components of adipose tissue and actively participate in its activities. Adipose
      tissue is known to express and secrete a variety of products known as
      'adipokines', including leptin, adiponectin, resistin and visfatin, as well as
      cytokines and chemokines such as tumor necrosis factor-alpha, interleukin-6 and
      monocyte chemoattractant protein-1. The release of adipokines by either
      adipocytes or adipose tissue-infiltrated macrophages leads to a chronic
      subinflammatory state that could play a central role in the development of
      insulin resistance and type 2 diabetes, and the increased risk of cardiovascular
      disease associated with obesity.

PMID- 18093862
TI  - Antibody profiling in plague patients by protein microarray.
AB  - A protein microarray containing 144 known or putative virulence-related proteins
      of Yersinia pestis was used to evaluate the antibody responses of plague
      patients. Forty-two proteins were found to be expressed in vivo and antibodies
      against 14 of them were detected in all patients analyzed, providing potential
      candidates for novel protective antigens and novel serodiagnostic markers in Y.
      pestis. Moreover, the lack of antibody to LcrV in the five patients in Focus F
      might be a challenge to our understanding of the pathogenesis of Y. pestis.

PMID- 18093863
TI  - A particular form of septic arthritis: septic arthritis of facet joint.
AB  - Only about 40 cases of septic arthritis of the facet joints have been reported to
      date. We report 6 new cases including 2 at the cervical spine, which is rarely
      involved. Mean age was 61.5 years; there were 5 men and 1 woman. Spinal pain and
      stiffness, fever, and asthenia were the presenting manifestations. Laboratory
      tests consistently showed inflammation. Among classical risk factors for
      infection, only noninsulin-dependent diabetes was noted, in a single patient.
      Mean time to the diagnosis was 42 days. Discitis, a far more common condition,
      was considered initially, and early radiographs were of limited diagnostic
      assistance. Radionuclide bone scans identified the site of the infection and
      served to look for other foci. Magnetic resonance imaging was effective in
      confirming the diagnosis at an early stage and in looking for local spread
      (muscles, epidural space, and disk). L3-L4 was involved in 3 patients, C4-C5 in
      2, and L4-L5 in 1. Direct inoculation during mesotherapy sessions was the cause
      in 1 patient. Cultures of blood and needle biopsy samples were positive in all 6
      cases; Staphylococcus aureus was the causative agent in 3 patients. The risk of
      local and systemic complications governs the prognosis of facet joint infection.
      Of our 6 patients, 4 experienced complications: there was 1 case each of
      discitis, epidural infection, endocarditis, and septic arthritis of the
      acromioclavicular joint. Fatal multiple organ dysfunction occurred in 1 patient.
      In the other 5 patients, antimicrobial therapy and protection from weight-bearing
      for 3 months ensured a favorable outcome.

PMID- 18093864
TI  - Improved extraction of vegetable oils under high-intensity ultrasound and/or
      microwaves.
AB  - Ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE)
      techniques have been employed as complementary techniques to extract oils from
      vegetable sources, viz, soybean germ and a cultivated marine microalga rich in
      docosahexaenoic acid (DHA). Ultrasound (US) devices developed by ourselves,
      working at several frequencies (19, 25, 40 and 300 kHz), were used for US-based
      protocols, while a multimode microwave (MW) oven (operating with both open and
      closed vessels) was used for MAE. Combined treatments were also studied, such as
      simultaneous double sonication (at 19 and 25 kHz) and simultaneous US/MW
      irradiation, achieved by inserting a non-metallic horn in a MW oven. Extraction
      times and yields were compared with those resulting from conventional procedures.
      With soybean germ the best yield was obtained with a 'cavitating tube' prototype
      (19 kHz, 80 W), featuring a thin titanium cylinder instead of a conventional
      horn. Double sonication, carried out by inserting an immersion horn (25 kHz) in
      the same tube, improved the yield only slightly but halved the extraction time.
      Almost comparable yields were achieved by closed-vessel MAE and simultaneous
      US/MW irradiation. Compared with conventional methods, extraction times were
      reduced by up to 10-fold and yields increased by 50-500%. In the case of marine
      microalgae, UAE worked best, as the disruption by US of the tough algal cell wall
      considerably improved the extraction yield from 4.8% in soxhlet to 25.9%. Our
      results indicate that US and MW, either alone or combined, can greatly improve
      the extraction of bioactive substances, achieving higher efficiency and shorter
      reaction times at low or moderate costs, with minimal added toxicity.

PMID- 18093865
TI  - Lung cysteine cathepsins: intruders or unorthodox contributors to the kallikrein
      kinin system?
AB  - The protease/antiprotease balance is tipped in favor of enhanced proteolysis in
      inflammatory lung disorders, promoting the spread and severity of inflammation.
      Cysteine cathepsins participate in the remodeling and/or degradation of the
      pulmonary extra cellular matrix and in lung homeostasis. There is now good
      evidence that cathepsins are involved in fibrosis, emphysema, asthma, and in
      bronchopulmonary dysplasia. Kinins are inflammatory mediators that induce edema,
      pain and vasodilatation, and participate in vascular homeostasis. Kinins may also
      contribute to the immune system by acting as danger signals, and activating
      bradykinin receptors. Kinins are believed to play a role in inflammatory
      obstructive airway diseases, asthma, and allergic rhinitis. Their release by
      plasma and tissue kallikreins is severely reduced at inflammatory sites, although
      local kinin production seems to remain intact. Such conflicting observations
      suggest that there are alternative mechanisms of kinin metabolism besides the
      classical pathways. This article reviews the biological and pathophysiological
      roles of lung cysteine cathepsins, kinins and their receptors, and summarizes the
      indications that cysteine cathepsins may contribute to kinin liberation and/or
      degradation.

PMID- 18093866
TI  - The lens epithelium: focus on the expression and function of the alpha-crystallin
      chaperones.
AB  - Lens epithelial cells are the parental cells responsible for growth and
      development of the transparent ocular lens. Many elegant investigations into
      their biology have focused on the factors that initiate and regulate lens
      epithelial cell differentiation. Because they serve key transport and cell
      maintenance functions throughout life, and are the primary source of metabolic
      activity in the lens, mechanisms to maintain lens epithelial cell integrity and
      survival are critical for lens transparency. The molecular chaperones alpha
      crystallins are abundant proteins synthesized in the differentiated lens fiber
      cell cytoplasm. However, their expression in lens epithelial cells has only been
      appreciated very recently. Besides their important roles in the refractive and
      light focusing properties of the lens, alpha-crystallins have been implicated in
      a number of non-refractive pathways including those involving stress response,
      apoptosis and cell survival. The most convincing evidence for their importance in
      the lens epithelium has been shown by studies on the properties of lens
      epithelial cells from alphaA and alphaB-crystallin gene knockout mice. Novel
      combination of genetics, cell and molecular biology should lead to a greater
      understanding of how lens epithelial cells proliferate, differentiate and
      survive.

PMID- 18093867
TI  - Continuous exposure to bisphenol A during in vitro follicular development induces
      meiotic abnormalities.
AB  - Bisphenol A (BPA), a widely used environmental contaminant, may exert weak
      estrogenic, anti-androgenic and anti-thyroidic activities. BPA is suspected to
      possess aneugenic properties that may affect somatic cells and mammalian oocytes.
      Oocyte growth and maturation depend upon a complex bi-directional signaling
      between the oocyte and its companion somatic cells. Consequently, disturbances in
      oocyte maturation may originate either from direct effects of BPA at the level of
      the oocyte or from indirect influences at the follicular level, such as
      alterations in hormonal homeostasis. This study aimed to analyze the effects of
      chronic BPA exposure (3 nM to 30 microM) on follicle-enclosed growth and
      maturation of mouse oocytes in vitro. Oocytes were cultured and their spindle and
      chromosomes were stained by alpha-tubulin immunofluorescence and ethidium
      homodimer-2, respectively. Confocal microscopy was utilized for subsequent
      analysis. Only follicles that were exposed to 30 microM BPA during follicular
      development showed a slightly reduced granulosa cell proliferation and a lower
      total estrogen production, but they still developed and formed antral-like
      cavities. However, 18% of oocytes were unable to resume meiosis after stimulation
      of oocyte maturation, and 37% arrested after germinal vesicle breakdown,
      significantly different from controls (p<0.05). Only 45% of the oocytes extruded
      a first polar body (p < 0.05). 30 microM BPA led also to a significant increase
      in meiosis I-arrested oocytes with unaligned chromosomes and spindle aberrations.
      Oocytes that were able to progress beyond meiosis I, frequently arrested at an
      abnormal telophase I. Additionally, in many oocytes exposed to low chronic BPA
      that matured to meiosis II chromosomes failed to congress at the spindle equator.
      In conclusion, mouse follicle culture reveals non-linear dose-dependent effects
      of BPA on the meiotic spindle in mouse oocytes when exposure was chronic
      throughout oocyte growth and maturation.

PMID- 18093868
TI  - Aneuploidy in upper gastro-intestinal tract cancers--a potential prognostic
      marker?
AB  - Chromosomal instability manifesting as aneuploidy is the most frequently observed
      abnormality in solid tumours. However, the role of aneuploidy as a cause or
      consequence of cancer remains a controversial topic. In this review, we focus on
      the karyotypic imbalances recorded for cancers of the upper gastro-intestinal
      (GI) tract, together with their associated pre-malignant lesions and the
      potential of aneuploidy as a clinical tool for patient management. Numeric
      chromosomal aberrations are common throughout gastro-oesophageal cancers and
      their precursor lesions. Additionally, specific chromosomal aneusomies have been
      identified as early changes in pre-dysplastic tissues suggesting they may be
      actively involved in driving tumourigenesis. As a progressive increase in the
      severity of aneuploidy with neoplastic progression has also been observed, it has
      thus been shown to be a useful prognostic indicator for patient classification as
      low or high-risk cases for cancer development. However, the biological basis for
      the aneuploidy in cancers of the upper GI tract needs to be established to
      understand its consequences and role during carcinogenesis, which is necessary
      for improving diagnostics and establishing novel targeted therapies.

PMID- 18093869
TI  - The Duisburg birth cohort study: influence of the prenatal exposure to PCDD/Fs
      and dioxin-like PCBs on thyroid hormone status in newborns and neurodevelopment
      of infants until the age of 24 months.
AB  - Prenatal exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzo
      p-dioxins and dibenzofurans (PCDD/Fs) can affect neurobehavioral development of
      infants and children. This effect may be mediated through disruption of thyroid
      hormone homeostasis. However, epidemiological studies reveal no consistent
      influence of PCDD/Fs and PCBs on thyroid status and neurodevelopment at
      environmental background levels. The effects may resolve with time of further
      decreasing exposure to these compounds. The aim of this study was to find out if
      there are still effects related to prenatal PCDD/F and PCB observable at the
      meanwhile decreased levels of exposure by using the same methods which have been
      applied in similar studies during the last 10 years in Europe. The birth cohort
      study was initiated in the year 2000 in the industrialized city of Duisburg,
      Germany. 232 healthy mother-infant pairs were recruited between 2000 and 2002.
      Dioxins, dioxin-like PCBs and six indicator PCBs were analyzed in maternal blood
      during pregnancy and in maternal milk following extraction and sample clean-up by
      HRGC/HRMS. Thyroid stimulating hormone (TSH), total thyroxine (T4), total
      triiodothyronine (T3), free thyroxine (FT4) and free triiodothyronine (FT3) were
      measured in serum samples of the pregnant women and in cord serum samples by
      chemiluminescent immunometric assay. Neurological examinations were performed at
      ages 2 weeks and 18 months using the neurological optimality score (NOS), mental
      and motor development were assessed using the Bayley Scales of Infant Development
      (BSID) at ages 12 and 24 months. Multiple linear regression analysis was used to
      describe the association of PCDD/F and PCB in maternal blood or milk with the
      outcome measurements after adjustment for confounding. Blood levels (n=182) of
      WHO 2005 toxic equivalents (TEQ) (PCDD/F+PCB) were in the range of 3.8-58.4
      pg/glipid base (median: 19.3 pg/glipid base). The corresponding data for human
      milk (n=149) were 2.6-52.4 pg/glipid base (median: 19.7 pg/glipid base). Multiple
      regression analysis showed no decrease of thyroid hormones related to WHO 2005
      TEQ in blood and milk of mothers and their newborns. Furthermore, no associations
      between exposure and neurological and developmental measures were observed. This
      study supports the view that the current decreased exposure to PCDD/Fs and PCBs
      does not impair thyroid function of newborns and neurodevelopment of infants
      until the age of 24 months.

PMID- 18093870
TI  - A new hybrid double divisor ratio spectra method for the analysis of ternary
      mixtures.
AB  - A new spectrophotometric method was developed for the simultaneous determination
      of ternary mixtures, without prior separation steps. This method is based on
      convolution of the double divisor ratio spectra, obtained by dividing the
      absorption spectrum of the ternary mixture by a standard spectrum of two of the
      three compounds in the mixture, using combined trigonometric Fourier functions.
      The magnitude of the Fourier function coefficients, at either maximum or minimum
      points, is related to the concentration of each drug in the mixture. The
      mathematical explanation of the procedure is illustrated. The method was applied
      for the assay of a model mixture consisting of isoniazid (ISN), rifampicin (RIF)
      and pyrazinamide (PYZ) in synthetic mixtures, commercial tablets and human urine
      samples. The developed method was compared with the double divisor ratio spectra
      derivative method (DDRD) and derivative ratio spectra-zero-crossing method
      (DRSZ). Linearity, validation, accuracy, precision, limits of detection, limits
      of quantitation, and other aspects of analytical validation are included in the
      text.

PMID- 18093871
TI  - Multiplex real-time PCR for detection of respiratory tract infections.
AB  - BACKGROUND: Broad diagnostics of respiratory infection by molecular assays has
      not yet won acceptance due to technical difficulties and high costs. OBJECTIVES:
      To evaluate clinical applicability of multiplex real-time PCR. STUDY DESIGN: An
      assay targeting influenza virus A (IfA) and B (IfB), parainfluenza 1-3 (PIV),
      human metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RV),
      enterovirus (EV), adenovirus (AdV), human coronaviruses (229E, OC43, NL63), M.
      pneumoniae and Ch. pneumoniae was developed and run daily on consecutive clinical
      nasopharyngeal swab samples. RESULTS: An etiology was identified in 48% of the
      954 samples, with IfA in 25%, RV in 20%, MPV in 10% and M. pneumoniae in 10% of
      the positive. By a rational procedure costs could be reduced and the customer
      price set relatively low (euro33 per sample). CONCLUSION: Streamlined testing and
      cost limitation is achievable and probably critical for implementation of a broad
      molecular diagnostics of respiratory infections.

PMID- 18093872
TI  - Spontaneous HCV clearance in HCV/HIV-1 coinfection associated with normalized CD4
      counts, low level of chronic immune activation and high level of T cell function.
AB  - BACKGROUND/OBJECTIVE: Spontaneous HCV clearance in HCV/HIV-1 coinfected patients
      is likely to be very rare given the damage to the immune system caused by HIV-1
      infection. The search for immune correlates of spontaneous clearance is important
      for the understanding of pathogenesis as well as for the development of possible
      new treatment strategies. STUDY DESIGN/RESULTS: A cohort of HCV/HIV-1 coinfected
      patients was followed. Plasma HCV viral load was measured and T cell immunity in
      peripheral blood samples was assessed using multi-color flow cytometry. One
      HCV/HIV-1 coinfected patient spontaneously became HCV-RNA negative after being
      positive for several years. This patient displayed a normalized CD4 counts on
      successful HAART, low level of T cell activation and a high level of T cell
      function as compared to HCV/HIV-1 coinfected control subjects. CONCLUSIONS: A
      beneficial immune status including a low level of chronic T cell activation and a
      high level of T cell function may be one factor that contributes to improved
      chances of clearance of chronic HCV infection in HIV-1 infected patients.

PMID- 18093873
TI  - Sleep duration and body mass index.

PMID- 18093874
TI  - Sleep-disordered breathing and reductions in renal function: are they associated
      in the elderly?

PMID- 18093876
TI  - Effects of rest duration between sets of resistance training on acute hormonal
      responses in trained women.
AB  - This study investigated the acute hormonal response to three different rest
      periods between sets of a traditional lower body resistance training session in
      young women. Twelve healthy trained females (26.83+/-3.93 years) participated in
      the study. On three separate sessions of a lower body resistance exercise
      protocol, subjects were assigned in a random order a rest interval of 30s (P30),
      60s (P60) or 120s (P120) between sets. The resistance exercise session consisted
      of four lower body exercises with three sets performed until contractile failure
      using 10-repetition maximum (RM) load. Blood samples were drawn for determination
      of serum growth hormone (GH) and cortisol concentrations before exercise (T0),
      immediately after each training session (T1), and after 5min (T5), 15min (T15),
      and 30min (T30) of recovery. Statistical evaluation of the area under the time
      concentration relationship for GH (GHauc) and for cortisol (Cauc) were analyzed
      using a one-way ANOVA There were no differences among protocols (P30, P60 and
      P120) in the serum GH and cortisol concentrations at baseline (T0). However, as
      compared to T0, all protocols led to acute increases (p<0.05) in serum GH
      concentrations after each training session. The GHauc was greater for P30 than
      for both P60 and P120, however, there were no differences between P60 and P120.
      The Cauc were not different among protocols. Thus, the magnitude of acute GH
      responses in previously strength-trained women appears greater with a 30-s rest
      interval between sets compared to longer rest periods of 60- or 120-s.

PMID- 18093877
TI  - Hybrid particle swarm optimization and tabu search approach for selecting genes
      for tumor classification using gene expression data.
AB  - Gene expression data are characterized by thousands even tens of thousands of
      measured genes on only a few tissue samples. This can lead either to possible
      overfitting and dimensional curse or even to a complete failure in analysis of
      microarray data. Gene selection is an important component for gene expression
      based tumor classification systems. In this paper, we develop a hybrid particle
      swarm optimization (PSO) and tabu search (HPSOTS) approach for gene selection for
      tumor classification. The incorporation of tabu search (TS) as a local
      improvement procedure enables the algorithm HPSOTS to overleap local optima and
      show satisfactory performance. The proposed approach is applied to three
      different microarray data sets. Moreover, we compare the performance of HPSOTS on
      these datasets to that of stepwise selection, the pure TS and PSO algorithm. It
      has been demonstrated that the HPSOTS is a useful tool for gene selection and
      mining high dimension data.

PMID- 18093878
TI  - Lamotrigine in clinical practice: long-term experience in patients with
      refractory epilepsy referred to a tertiary epilepsy center.
AB  - Lamotrigine (LTG, Lamictal), one of the newer antiepileptic drugs, was admitted
      to the Dutch market in 1996. It was first used as adjunctive therapy and later as
      a monotherapy in partial and generalized epilepsy. All patients who started on
      LTG in 1996 or 1997 in the Epilepsy Centre Kempenhaeghe (n=314) were enrolled in
      this study and followed for 48 months. The data indicate that the retention rates
      for LTG after 1, 2, 3, and 4 years are respectively 74.4, 69.3, 63.1, and 55.6%.
      Patients with normal cognitive function were more likely to continue than
      patients with mental retardation. The main reason for discontinuing LTG therapy
      was lack of efficacy (19.1%). Four patients (1.4%) were seizure-free for the
      total follow-up period of 48 months. The most frequently reported negative side
      effects were dizziness and headache, both in patients who continued and in those
      who discontinued therapy. A large percentage of patients also reported positive
      side effects like "feeling/being more active" and "feeling more clear/more
      responsive." For the whole patient group, the plasma level of LTG was measured
      277 times. Plasma levels of LTG were influenced by the patients' comedications.
      Plasma levels of LTG in groups taking LTG in monotherapy, LTG plus an inducer,
      and LTG plus valproate were 8.7, 4.8, and 8.7 mg/L, respectively. The correlation
      between measured plasma level and dose confirm the manufacturer's dose
      recommendations. The manufacturer recommends half the dosage of lamotrigine
      monotherapy when the patient also uses valproate. When the patient uses an
      inducer, the dosage of LTG must be two times the dose used in monotherapy.

PMID- 18093879
TI  - Low nanomolar concentration of mercury chloride increases vascular reactivity to
      phenylephrine and local angiotensin production in rats.
AB  - Exposure to mercury at nanomolar level affects cardiac function but its effects
      on vascular reactivity have yet to be investigated. Pressor responses to
      phenylephrine (PHE) were investigated in perfused rat tail arteries before and
      after treatment with 6 nM HgCl2 during 1 h, in the presence (E+) and absence (E-)
      of endothelium, after L-NAME (10(-4) M), indomethacin (10(-5 )M), enalaprilate (1
      microM), tempol (1 microM) and deferoxamine (300 microM) treatments. HgCl2
      increased sensitivity (pD2) without modifying the maximum response (Emax) to PHE,
      but the pD2 increase was abolished after endothelial damage. L-NAME treatment
      increased pD2 and Emax. However, in the presence of HgCl2, this increase was
      smaller, and it did not modify Emax. After indomethacin treatment, the increase
      of pD2 induced by HgCl2 was maintained. Enalaprilate, tempol and deferoxamine
      reversed the increase of pD2 evoked by HgCl2. HgCl2 increased the angiotensin
      converting enzyme (ACE) activity explaining the result obtained with
      enalaprilate. Results suggest that at nanomolar concentrations HgCl2 increase the
      vascular reactivity to PHE. This response is endothelium mediated and involves
      the reduction of NO bioavailability and the action of reactive oxygen species.
      The local ACE participates in mercury actions and depends on the angiotensin II
      generation.

PMID- 18093880
TI  - BioLattice: a framework for the biological interpretation of microarray gene
      expression data using concept lattice analysis.
AB  - MOTIVATION: A challenge in microarray data analysis is to interpret observed
      changes in terms of biological properties and relationships. One powerful
      approach is to make associations of gene expression clusters with biomedical
      ontologies and/or biological pathways. However, this approach evaluates only one
      cluster at a time, returning long unordered lists of annotations for clusters
      without considering the overall context of the experiment under investigation.
      RESULTS: BioLattice is a mathematical framework based on concept lattice analysis
      for the biological interpretation of gene expression data. By considering gene
      expression clusters as objects and associated annotations as attributes and by
      using set inclusion relationships BioLattice orders them to create a lattice of
      concepts, providing an 'executive' summary of the experimental context. External
      knowledge resources such as Gene Ontology trees and pathway graphs can be added
      incrementally. We propose two quantitative structural analysis methods,
      'prominent sub-lattice' and 'core-periphery' analyses, enabling systematic
      comparison of experimental concepts and contexts. BioLattice is implemented as a
      web-based utility using Scalable Vector Graphics for interactive visualization.
      We applied it to real microarray datasets with improved biological
      interpretations of the experimental contexts.

PMID- 18093881
TI  - The in-flow capture of superparamagnetic nanoparticles for targeting
      therapeutics.
AB  - Superparamagnetic nanoparticles have been synthesized that could potentially be
      used to magnetically target therapeutics within the body. The magnetic targeting
      and successful in-flow capture of 330-nm and 580-nm agglomerates of these
      magnetite nanoparticles was performed using a 0.5-T magnet. Optical observation
      of magnetic nanoparticle capture in microcapillary flow provides a useful
      preliminary way of establishing conditions for the magnetic capture of
      nanoparticles with direct relevance to blood vessels for magnetically directed
      therapy. A stable nanoparticle layer of 580-nm agglomerates could be formed at
      mean capillary flow velocities of up to 2.5 cm s(-1) and for the 330-nm
      agglomerates at velocities up to 4.4 cm s(-1). These data show that smaller
      nanoparticle agglomerates form a layer that is impervious to erosion by fluid
      shear. Capillary blocking by nanoparticles, analogous to an embolism, was not
      detected in these experiments.

PMID- 18093883
TI  - The phylogenetic information profile of HIV-1 and the degradation effect of
      recombination.
AB  - HIV-1, while known to recombine frequently and evolve rapidly, is one of the most
      sequenced organisms. The availability of many and long sequences (almost full
      length) renders HIV-1 as a good model for studying theoretical predictions linked
      to evolution and phylogenetic inferences. Here we study the effects of rapid and
      through-recombination evolution on phylogenetic information in order to confirm
      theoretical predictions of the characteristics of phylogenetic information on a
      real dataset. Firstly we study the fluctuation of the phylogenetic information
      along the HIV-1 genome showing that genomic regions such as the first part and
      the last part of the pol gene contain less phylogenetic information, while the
      vpr, vpu and the first exon of the tat gene contain more phylogenetic information
      compared to the rest of the genome. Moreover, we provide evidence that
      phylogenetic information is correlated to the sequence similarity of the dataset
      used and is degraded by the effect of recombination.

PMID- 18093882
TI  - Nucleotide sequence polymorphism in circoviruses.
AB  - Analysis of nucleotide diversity within six species of circovirus showed
      consistently stronger purifying selection at nonsynonymous sites in the rep gene
      than on those in the cap gene. In addition, synonymous nucleotide diversity in
      the rep gene was significantly lower than that in the cap gene, suggesting
      functional constraint even at synonymous sites in rep, which was associated in
      all six species with strongly negative AT-skew. Of the six virus species
      examined, four species showed evidence of ongoing purifying selection at
      nonsynonymous polymorphic sites in the rep gene, indicating the presence of
      slightly deterious nonsynonymous variants in these populations. The rep gene of
      porcine circovirus 2 (PCV2) was unique, however, in showing a strong excess of
      rare nonsynonymous polymorphisms. The excess of rare nonsynonymous polymorphisms
      suggests a prolonged population bottleneck in PCV2, allowing slightly deleterious
      mutations to accumulate, followed by a population expansion during which
      selection to remove these variants has increased in effectiveness. Such a
      population history is consistent with the epidemiological evidence of a recent
      worldwide spread of PCV2.

PMID- 18093884
TI  - Association of interleukin-10 gene haplotypes with Pseudomonas aeruginosa airway
      colonization in cystic fibrosis.
AB  - We genotyped three polymorphisms of the promoter region of the interleukin-10 (IL
      10) gene in 220 CF patients from the CF Center of Bari, and tested for an
      association between genetic variants of the cytokine and chronic airway
      colonization with Pseudomonas aeruginosa. We found that carriers of the high-IL
      10-producing-GCC haplotype had significantly higher risk of chronic pulmonary
      infection with the pathogen.

PMID- 18093885
TI  - Simultaneous determination of microcystin-LR and its glutathione conjugate in
      fish tissues by liquid chromatography-tandem mass spectrometry.
AB  - A sensitive and selective liquid chromatography-tandem mass spectrometry method
      was developed and validated for the simultaneous quantitative determination of
      microcystin-LR (MC-LR) and its glutathione conjugate (MC-LR-GSH) in fish tissues.
      The analytes were extracted from fish liver and kidney using 0.01M EDTA-Na(2)-5%
      acetic acid, followed by a solid-phase extraction (SPE) on Oasis HLB and silica
      cartridges. High-performance liquid chromatography (HPLC) with electrospray
      ionization mass spectrometry, operating in selected reaction monitoring (SRM)
      mode, was used to quantify MC-LR and its glutathione conjugate in fish liver and
      kidney. Recoveries of analytes were assessed at three concentrations (0.2, 1.0,
      and 5microg g(-1) dry weight [DW]) and ranged from 91 to 103% for MC-LR, and from
      65.0 to 75.7% for MC-LR-GSH. The assay was linear within the range from 0.02 to
      5.0microg g(-1) DW, with a limit of quantification (LOQ) of 0.02microg g(-1) DW.
      The limit of detection (LOD) of the method was 0.007microg g(-1) DW in both fish
      liver and kidney. The overall precision was determined on three different days.
      The values for within- and between-day precision in liver and kidney were within
      15%. This method was applied to the identification and quantification of MC-LR
      and its glutathione conjugate in liver and kidney of fish with acute exposure of
      MC-LR.

PMID- 18093886
TI  - ER-beta expression in large bowel adenomas: implications in colon carcinogenesis.
AB  - BACKGROUND: A pivotal role of oestrogen receptor-beta has been suggested in colon
      carcinogenesis in humans. However, few data are available on oestrogen receptor
      beta in colorectal pre-cancerous lesions. AIM: In the present study, we evaluated
      oestrogen receptor-beta expression and its possible correlation with
      proliferative activity and apoptosis in colorectal adenomas and normal colon
      tissue. PATIENTS/METHODS: Adenomatous tissue from 25 patients with colonic
      polyps, and normal tissue from 25 controls were used. Oestrogen receptor-beta
      expression, colonocyte proliferation (expressed as PCNA positivity) and apoptosis
      were evaluated. RESULTS: In adenomatous tissue, a significant reduction of
      oestrogen receptor-beta was observed compared to normal mucosa (10.1+/-5.5% vs.
      44.2+/-13.7; p<0.03), while the expression of oestrogen receptor-alpha remained
      unvaried. Cell proliferative activity significantly increased in adenomatous
      tissue compared to normal mucosa (59.3+/-7.1 vs. 18.5+/-8.8; p<0.0001), doubling
      the PCNA/apoptosis ratio. An inverse correlation was found between oestrogen
      receptor-beta and PCNA expression in adenomas (r=-0.81), a datum confirmed by
      confocal microscopy evaluation. CONCLUSIONS: Our data demonstrate, for the first
      time, a significant reduction of oestrogen receptor-beta expression already in
      the pre-cancerous phase of colon carcinogenesis. This suggests a role of
      selective oestrogen receptor-beta agonists in the prevention of colorectal
      cancer.

PMID- 18093887
TI  - [Living-donor kidney transplantation in children].
AB  - Living-donor transplantation has several obvious advantages for children: better
      graft-survival than cadaveric-transplantation, the possibility to be pre-emptive
      and avoid dialysis and its burden to the child, to be programmed during school
      holidays. However, its negative aspects must not be ignored. They are mainly
      psychological and concern the adolescent. The affective burden of both living
      donation and transplantation is so strong that a psychological check-up is
      mandatory for the donor but also for the recipient and even the non-donor parent.
      In the medical evaluation of the donor, specific explorations, such as the search
      of a genetic mutation, could be necessary in the case of hereditary renal
      disease.

PMID- 18093888
TI  - [Transplantation from a living related donor: Results].
AB  - The results of transplantation from a living donor (LDT) are constantly better
      than those of cadaveric transplantation (2004 Report of the French Agency of
      Biomedicine: graft survival 80 versus 63% at 10 years). Transplantation from an
      HLA-identical sibling is in any case the best combination, but there is no
      significant difference in graft survival when the donor is a parent, a child, a
      non HLA-identical sibling, a spouse or an unrelated person. The reasons for these
      better results are several: the quality of the kidney transplant, the absence of
      brain death, the advantage of a programmed surgery and of preemptive
      transplantation. It is admitted now that HLA compatibility plays a minor role. As
      in cadaveric transplantation, acute rejection, delayed graft function,
      pretransplant HLA immunisation, age of the donor and the recipient and possibly
      the discrepancy between the weight of the donor and the recipient are
      determinants of transplant outcome.

PMID- 18093889
TI  - P2Y receptors activated by diadenosine polyphosphates reestablish Ca(2+)
      transients in achondroplasic chondrocytes.
AB  - Achondroplasia is the most common type of dwarfism, characterised by a mutation
      in the gene that encodes the fibroblast growth factor receptor 3 (FGFR3).
      Achondroplasia mainly affects the chondrocytes and therefore bones do not grow
      properly since intracellular pathways are altered. In this sense, defective
      calcium signaling by mutant FGFR3 has been previously described. The purpose of
      this study was to investigate the presence of purinergic P2Y receptors and how
      the activation of these receptors can have influence on defective calcium
      signaling observed in achondroplasic chondrocytes. The presence of P2Y receptors
      was determined by immunocytochemical and western blot techniques. Calcium
      mobilization after stimulation with nucleotides, dinucleotides, or, FGF9
      application, was measured using the ratiometric dye fura-2/AM and fluorescence
      imaging. Our results demonstrate the expression of P2Y(1), P2Y(2), P2Y(6) and
      P2Y(11) receptors in achondroplasic chondrocytes, as well as the activation of
      these receptors after nucleotides and dinucleotides exposure. The altered calcium
      signaling of achondroplasic chondrocytes was confirmed, since FGF9 treatment
      fails to induce calcium mobilization. However, achondroplasic chondrocytes pre
      treated with Ap(4)A are able to respond with increases in intracellular calcium
      after FGF9 stimulation. These findings show the rescue effect of diadenosine
      tetraphosphate (Ap(4)A), acting by means of P2Y receptors, on defective calcium
      response triggered by achondroplasic FGFR3.

PMID- 18093890
TI  - The influence of exercise during growth on ultrasonographic parameters of the
      superficial digital flexor tendon of young Thoroughbred horses.
AB  - REASON FOR PERFORMING STUDY: Conditioning by early training may influence the
      composition of certain musculoskeletal tissues, but very few data exist on its
      effect during growth on tendon structure and function. OBJECTIVES: To investigate
      whether conditioning exercise in young foals would lead to any
      ultrasonographically detectable damage to the superficial digital flexor tendon
      or an increase in cross-sectional area (CSA). METHODS: Thirty-three Thoroughbred
      foals reared at pasture were allocated to 2 groups: control (PASTEX) allowed
      exercise freely at pasture; and CONDEX, also at pasture, began conditioning
      exercise from mean age 21 days over 1030 m on a purpose-built oval grass track,
      for 5 days/week until mean age 18 months. Foals were observed daily, and
      underwent orthopaedic examination monthly. Ultrasonographic images of the
      superficial digital flexor tendon (SDFT) at the mid-metacarpal level of both
      forelimbs were obtained in all foals at ages 5, 8, 12, 15 and 18 months. CSA was
      validated (r(2) = 0.89) by determining CSA from digital photographs of the
      transected SDFT surface from 12 of the horses necropsied at age 17.1 months.
      RESULTS: here was no clinical or ultrasonographic evidence of tendonopathy in
      either group and the greatest increase in mean CSA in both groups occurred
      between age 5 and 8 months. Across all age categories, there was no significant
      difference in mean CSA between the left and right limbs, or colts and fillies;
      there was a trend towards a larger CSA in the CONDEX group (P = 0.058).
      CONCLUSIONS: There was no conclusive evidence for a structural adaptive
      hypertrophy of the SDFT, probably because the regimen was insufficiently rigorous
      or because spontaneous pasture exercise may induce maximal development of energy
      storing tendons. POTENTIAL RELEVANCE: A moderate amount of early conditioning
      exercise against a background of constant exercise at pasture is not harmful to
      the development of the flexor tendons.

PMID- 18093891
TI  - Effects of exercise on tenocyte cellularity and tenocyte nuclear morphology in
      immature and mature equine digital tendons.
AB  - REASON FOR PERFORMING STUDY: The injury-prone, energy-storing equine superficial
      digital flexor tendon (SDFT) of the mature performance horse has a limited
      ability to respond to exercise in contrast with the noninjury-prone, anatomically
      opposing common digital extensor tendon (CDET). Previous studies have indicated
      low levels of cellular activity in the mature SDFT, but in foal tendons the
      tenocytes may still have the ability to adapt positively to increased exercise.
      OBJECTIVES: To measure tenocyte densities and types in histological sections from
      the SDFT and CDET of horses from controlled long-term, short-term and foal
      exercise studies. METHODS: Specimens were collected from mid-metacarpal segments
      of the CDET and SDFT for each horse and processed for histology; central and
      peripheral regions of the SDFT cross-section were analysed separately (SDFTc,
      SDFTp). Tenocyte nuclei were counted in a total area of 1.59 mm(2) for each
      tendon region in each horse. Each nucleus was classified as type 1 (elongate and
      thin), type 2 (ovoid and plump) or type 3 (chondrocyte-like); type 1 cells are
      proposed to be less synthetically active than type 2 cells. RESULTS: No
      significant differences were noted between exercise and control groups in any of
      the studies, with the exception of an exercise-related reduction in the
      proportion of type 1 tenocytes for all tendons combined in the long-term study.
      There were tendon- and site-specific differences in tenocyte densities and
      proportions of type 1 and 2 cells in all 3 studies. CONCLUSIONS AND POTENTIAL
      RELEVANCE: There was no indication that exercise increased tenocyte density or
      proportions of the (theoretically) more active type 2 cells in immature horses
      (short-term and foal studies), perhaps because the training regimens did not
      achieve certain threshold strain levels. In the foal study these findings can
      still be interpreted positively as evidence that the training regimen did not
      induce subclinical damage.

PMID- 18093892
TI  - Early exercise advances the maturation of glycosaminoglycans and collagen in the
      extracellular matrix of articular cartilage in the horse.
AB  - REASON FOR PERFORMING STUDY: Training at a very young age may influence the
      characteristics of the collagen network of articular cartilage extracellular
      matrix (ECM) in horses. OBJECTIVES: To investigate whether increasing workload of
      foals results in significant changes in the biochemical composition of articular
      cartilage ECM. METHODS: Thoroughbred foals (n = 33) were divided into 2 different
      exercise groups from age 10 days-18 months. One group (PASTEX; n = 15) was reared
      at pasture; the other (CONDEX; n = 18) underwent a specific additional training
      programme that increased workload by 30%. At mean age 18 months, 6 animals from
      each group were subjected to euthanasia. The proximal articular surface of the
      proximal phalanx of the right hindlimb was examined for the presence of damage
      using the cartilage degeneration index (CDI). Samples were taken from 2 sites
      with known different loading patterns. Slices were analysed for DNA,
      glycosaminoglycans (GAG), collagen and post translational modifications of
      collagen (formation of hydroxylysylpyridinoline [HP] and pentosidine crosslinks,
      and hydroxylysine [Hyl]), and exercise groups and different sites compared.
      RESULTS: There were no differences in CDI between PASTEX and CONDEX animals,
      indicating the absence of extra joint damage due to the exercise regimen. There
      were site-related differences for most biochemical variables, corroborating
      earlier reports. All biochemical variables showed differences between PASTEX and
      CONDEX groups at one of the sites, and some at both. GAG and collagen levels were
      lower in the CONDEX group whereas Hyl, HP crosslinks and pentosidine crosslinks
      were higher. CONCLUSIONS AND POTENTIAL RELEVANCE: A measurable effect of the
      conditioning exercise was demonstrated. The margin between too much and too
      little work when training foals may be narrower than intuitively presumed.

PMID- 18093893
TI  - Evaluation of a new strategy to modulate skeletal development in racehorses by
      imposing track-based exercise during growth: the effects on 2- and 3-year-old
      racing careers.
AB  - REASON FOR PERFORMING STUDY: No data exist on the effects of conditioning
      exercise at foal age on workload and subsequent clinical injury rate during their
      2- and 3-year-old racing careers. OBJECTIVES: To investigate the effects of
      subjecting TB foals to conditioning exercise prior to the start of race training
      on: the workload required to reach a level of fitness sufficient to compete; and
      the prevalence of orthopaedic injury during the first 2 seasons of their racing
      careers. METHODS: Twenty 18-month-old TBs, 12 subjected to conditioning exercise
      at foal age (CONDEX) and 8 exercised spontaneously at pasture only (PASTEX) were
      trained and entered in competitive events. Workload was quantified using the
      cumulative workload index (the product of average velocity and distance at a
      specific gait) and the animals were monitored clinically and radiographically for
      signs of musculoskeletal disorders. RESULTS: Workload to reach the desired
      fitness level was similar for CONDEX and PASTEX. CONDEX performed more prerace
      training sessions as 2-year-olds (P<0.05). The incidence of orthopaedic injuries
      was low in both groups and there were no differences in the occurrence of
      orthopaedic ailments. PASTEX animals tended to show signs of musculoskeletal
      disorders earlier than CONDEX animals. This time difference was significant for
      metacarpophalangeal joint pain on flexion, reduced carpal flexion and hindlimb
      lameness (P<0.05). CONCLUSIONS: Subjecting TB foals to conditioning exercise
      early in life does not have adverse effects on racing careers at ages 2 and 3
      years, and does not influence the workload needed to reach a fitness level that
      is sufficient for racing. POTENTIAL RELEVANCE: The lack of negative effects and
      the indications of some positive effects of early conditioning exercise in the
      Thoroughbred encourage further large-scale comparative studies.

PMID- 18093894
TI  - Evaluation of a new strategy to modulate skeletal development in Thoroughbred
      performance horses by imposing track-based exercise during growth.
AB  - REASON FOR PERFORMING STUDY: No data exist on the intensity of exercise required
      or on possible harmful effects of increasing exercise in foals over the natural
      level when free at pasture. OBJECTIVES: To investigate whether an increase in
      workload over free pasture exercise in the period from directly after birth to
      the start of training is tolerated by Thoroughbred (TB) foals without increasing
      injury rate or producing other undesired side effects. METHODS: Thirty-three TB
      foals were allocated to one of 2 exercise groups directly after birth. One group
      (PASTEX) was raised on pasture and the other (CONDEX) kept under identical
      circumstances, but was additionally subjected to an exercise protocol of
      gradually increasing intensity. Foals were monitored periodically and scored for
      the presence of clinical signs related to the musculoskeletal system (joint
      effusion, pain at flexion, occurrence of physeal swelling), and radiographs taken
      at the end of the conditioning phase. Also, behavioural studies were performed to
      detect any changes in behaviour related to the exercise programme. Cortisol
      levels were measured in both groups, to assess the level of stress. RESULTS:
      Workload in the CONDEX group was significantly higher than in the PASTEX group
      (approximately 30%). Conditioning increased the likelihood for joint effusion in
      the antebrachiocarpal joint, but reduced tarsocrural effusion and physeal
      swelling at the lateral distal radius, the third metacarpal bone (medial aspect)
      and lateral and medial aspects of the third metatarsal bone. CONCLUSIONS: The 30%
      increase in workload did not affect the animals' welfare, effects of conditioning
      exercise on clinical musculoskeletal health were few and there were no adverse
      effects. POTENTIAL RELEVANCE: This study supports the feasibility of imposing
      early conditioning exercise in horses and is a benchmark for its effects on the
      development of equine musculoskeletal tissues.

PMID- 18093895
TI  - [Methods for the assessment of adolescent obesity in epidemiological studies].
AB  - INTRODUCTION: The incidence of obesity is increasing dramatically not only among
      adults, but also in the child population. OBJECTIVE: Comparison of different
      anthropological methods. METHODS: The authors evaluated the data of 654 boys and
      584 girls (age 15-19 years). Body height and waist circumference were measured,
      body composition was determined using InBody3.0 bioimpedance instrument. Body
      mass index and body fat percentage were calculated by the instrument. RESULTS: On
      the basis of age and gender specific diagnostic criteria for body mass index,
      incidence of leanness, overweight and obesity in the boys' group were 6.7, 15.9
      and 4.1%, respectively. In the girls' group the respective figures were 7.2, 7.9
      and 1.9%. On the basis of body fat percentage, 5.1% of boys and 16.2% of girls
      were obese, whereas on the basis of data for waist circumference, visceral
      obesity occurred in 10.5% of boys and 7.9% of girls. In the overweight groups
      10.5% of boys and 77.0% of girls were obese on the basis of body fat percentage,
      whereas taking into consideration the values of waist circumference, 38% of boys
      and 55% of girls could be regarded as obese. CONCLUSIONS: The determination of
      body composition is of utmost importance in obesity screening and in the follow
      up slimming diets. In addition to this, simple and inexpensive waist
      circumference measurements should be performed in each instance.

PMID- 18093896
TI  - [Analysis of microalbuminuria with immunonephelometry and high performance liquid
      chromatography. Evaluation of new criteria].
AB  - INTRODUCTION: Hypertension as well as type 2 diabetes mellitus is a major factor
      in population mortality. Both diseases damage the endothelium, the early sign of
      which is microalbuminuria, which can be screened by dipstick and can be diagnosed
      by using immuno-based and high performance liquid chromatography methods. Using
      high performance liquid chromatography, the non-immunoreactive albumin can be
      detected as well. AIMS: The authors aimed at the examination of albuminuria in
      the case of immunonephelometrically negative patients with high performance
      liquid chromatography, in diabetic and hypertensive and non-diabetic hypertensive
      populations. The authors also wanted to compare the present (albumin-creatinine
      ratio: male: > or =2.5 mg/mmol, female: > or =3.5 mg/mmol) and a new criteria of
      the Heart Outcomes Prevention Evaluation study (patients without diabetes:
      immunological method, > or =0.7 mg/mmol; high performance liquid chromatography,
      > or =3.1 mg/mmol; individuals with diabetes: immunological method, > or =1.4
      mg/mmol; high performance liquid chromatography, > or =5.2 mg/mmol) of
      microalbuminuria. METHODS: Examination of fresh urines of 469 microalbuminuria
      negative patients by dipstick were performed by immunonephelometry. Patients, who
      were microalbuminuria negative by immunonephelometry as well, were further
      analyzed by high performance liquid chromatography using the Accumintrade mark
      Kit, based on size-exclusion chromatography. RESULTS: Three times higher
      albuminuria were found with high performance liquid chromatography than with
      immunonephelometry. The intraindividual coefficient of variation did not differ
      in the two methods (37 +/- 31% vs. 40 +/- 31%, p = 0.869; immunonephelometry vs.
      high performance liquid chromatography; mean +/- standard deviation). Using the
      present criteria for microalbuminuria, 43% of immunonephelometrically negative
      patients proved to be microalbuminuric by high performance liquid chromatography.
      Using the new criteria of the Heart Outcomes Prevention Evaluation study, the
      rate of microalbuminuria positivity among the immunonephelometrically negative
      patients decreased to 14.5% by high performance liquid chromatography and the
      decrease in the number of microalbuminuria positive cases by high performance
      liquid chromatography could be observed mainly in the diabetic and hypertensive
      group (49% vs. 7.5%), while slighter decrease could be observed in the non
      diabetic hypertensive group (37% vs. 26.5%). Applying the traditional criteria,
      the strongest predictor was the male gender by the logistic regression analysis.
      In 28% of microalbuminuria negative patients by immunonephelometry the diagnosis
      of microalbuminuria can be established using high performance liquid
      chromatography. CONCLUSIONS: Almost in one-third of microalbuminuria negative
      patients by immunonephelometry the diagnosis of microalbuminuria can be
      established by high performance liquid chromatography for which diagnosis three
      constitutive urine examinations are still needed. New criteria determined by the
      Heart Outcomes Prevention Evaluation study can be used neither in case of
      diabetic and hypertensive patients, nor in the case of non-diabetic hypertensive
      patients. The gender as the most important predictor of microalbuminuria cannot
      be ignored.

PMID- 18093897
TI  - [Imaging techniques for the pre- and postoperative evaluation of recipients with
      living-donor liver transplantation].
AB  - Whole-liver transplantation is a worldwide-accepted method for treatment of end
      stage liver disease. As a result of the shortage of cadaveric livers, split-liver
      transplantation and living-donor liver transplantation are becoming more common.
      Preoperative imaging of the donors and recipients are indispensable for surgery
      planning, while postoperative imaging highly contributes to the success of
      transplantation by follow-up the transplanted organ and early diagnosis of
      possible sequelae. The authors delineate both pre- and postoperative imaging of
      recipients of living-donor transplantation, including the role of conventional x
      ray, ultrasound, CT and MRI techniques, and also the different possibilities in
      the field of interventional radiology.

PMID- 18093898
TI  - [The epidemic of chronic kidney disease requires the estimation of glomerular
      filtration rate].
AB  - Nowadays chronic kidney disease has become a major public health problem due to
      the great increase in atherogenic nephropathies. In the absence of classic renal
      symptoms, chronic kidney disease is mostly diagnosed when renal failure is
      already advanced, although it can be revealed by laboratory tests in the earlier
      stages. When diagnosis is late, the progression to end-stage renal failure is
      unavoidable and renal replacement therapy is needed. Even early-moderate renal
      failure significantly increases the risks for atherosclerosis, thereby leading to
      the deaths of patients from cardiovascular disease before initiation of dialysis.
      Therefore screening for asymptomatic chronic kidney disease is urgently needed.
      Estimated glomerular filtration rate has the greatest importance in the screening
      and in the timely intervention to slow down the progression of renal failure and
      cardiovascular disease. In 2005, the Hungarian Society of Nephrologists and the
      Hungarian Society of Laboratory Medicine suggested the automatic estimation and
      reporting of glomerular filtration rate, each time serum creatinine measurements
      were made. This practice is used more frequently by laboratories in Hungary. This
      article aims to help facilitate the utilization and evaluation of estimated
      glomerular filtration rate.

PMID- 18093899
TI  - [Introduction of percutaneous kidney operation in Hungary in 1984].

PMID- 18093900
TI  - [Sudden death caused by rupture of the coronary artery in 1737, verified by
      autopsy--a case report by Daniel Fischer from Kesmark (Hungary)].

PMID- 18093902
TI  - [Interview with Dr. Laszlo Csiba].

PMID- 18093903
TI  - Exploring social contextual correlates of computer ownership and frequency of use
      among urban, low-income, public housing adult residents.
AB  - BACKGROUND: As advances in computer access continue to be made, there is a need
      to better understand the challenges of increasing access for racial/ethnic
      minorities, particularly among those with lower incomes. Larger social contextual
      factors, such as social networks and neighborhood factors, may influence computer
      ownership and the number of places where individuals have access to computers.
      OBJECTIVES: We examined the associations of sociodemographic and social
      contextual factors with computer ownership and frequency of use among 1554 adults
      living in urban public housing. METHODS: Bivariate associations between dependent
      variables (computer ownership and regular computer use) and independent variables
      were used to build multivariable logistic models adjusted for age and site
      clusters. RESULTS: Participants (N = total weighted size of 2270) were on average
      51.0 (+/- 21.4) years old, primarily African American or Hispanic, and earned
      less than US $20000 per year. More than half owned a computer, and 42% were
      regular computer users. Reporting computer ownership was more likely if
      participants lived above the poverty level (OR = 1.78, 95% CI = 1.39-2.29),
      completed high school (OR = 2.46, 95% CI = 1.70-3.55), were in financial hardship
      (OR = 1.38, 95% CI = 1.06-1.81), were employed and supervised others (OR = 1.94,
      95% CI = 1.08-3.46), and had multiple role responsibilities (OR = 2.18, 95% CI =
      1.31-3.61). Regular computer use was more likely if participants were non
      Hispanic (OR = 1.94, 95% CI = 1.30-2.91), lived above the poverty level (OR =
      2.84, 95% CI = 1.90-4.24), completed high school (OR = 4.43, 95% CI = 3.04-6.46),
      were employed and supervised others (OR = 2.41, 95% CI = 1.37-4.22), felt safe in
      their neighborhood (OR = 1.57, 95% CI = 1.08-2.30), and had greater social
      network ties (OR = 3.09, 95% CI = 1.26-7.59). CONCLUSIONS: Disparities in
      computer ownership and use are narrowing, even among those with very low incomes;
      however, identifying factors that contribute to disparities in access for these
      groups will be necessary to ensure the efficacy of future technology-based
      interventions. A unique finding of our study is that it may be equally as
      important to consider specific social contextual factors when trying to increase
      access and use among low-income minorities, such as social network ties,
      household responsibilities, and neighborhood safety.

PMID- 18093904
TI  - The contribution of teleconsultation and videoconferencing to diabetes care: a
      systematic literature review.
AB  - BACKGROUND: A systematic literature review was carried out to study the benefits
      of teleconsultation and videoconferencing on the multifaceted process of diabetes
      care. Previous reviews focused primarily on usability of technology and
      considered mainly one-sided interventions. OBJECTIVE: The objective was to
      determine the benefits and deficiencies of teleconsultation and videoconferencing
      regarding clinical, behavioral, and care coordination outcomes of diabetes care.
      METHODS: Electronic databases (Medline, PiCarta, PsycINFO, ScienceDirect,
      Telemedicine Information Exchange, ISI Web of Science, Google Scholar) were
      searched for relevant publications. The contribution to diabetes care was
      examined for clinical outcomes (eg, HbA(1c), blood pressure, quality of life),
      behavioral outcomes (patient-caregiver interaction, self-care), and care
      coordination outcomes (usability of technology, cost-effectiveness, transparency
      of guidelines, equity of care access). Randomized controlled trials (RCTs) with
      HbA(1c) as an outcome were pooled using standard meta-analytical methods.
      RESULTS: Of 852 publications identified, 39 met the inclusion criteria for
      electronic communication between (groups of) caregivers and patients with type 1,
      type 2, or gestational diabetes. Studies that evaluated teleconsultation or
      videoconferencing not particularly aimed at diabetes were excluded, as were those
      that described interventions aimed solely at clinical improvements (eg, HbA(1c)).
      There were 22 interventions related to teleconsultation, 13 to videoconferencing,
      and 4 to combined teleconsultation and videoconferencing. The heterogeneous
      nature of the identified videoconferencing studies did not permit a formal meta
      analysis. Pooled results from the six RCTs of the identified teleconsultation
      studies did not show a significant reduction in HbA(1c) (0.03%, 95% CI = - 0.31%
      to 0.24%) compared to usual care. There was no significant statistical
      heterogeneity among the pooled RCTs (chi(2) (7)= 7.99, P = .33). It can be
      concluded that in the period under review (1994-2006) 39 studies had a scope
      broader than clinical outcomes and involved interventions allowing patient
      caregiver interaction. Most of the reported improvements concerned satisfaction
      with technology (26/39 studies), improved metabolic control (21/39), and cost
      reductions (16/39). Improvements in quality of life (6/39 studies), transparency
      (5/39), and better access to care (4/39) were hardly observed. Teleconsultation
      programs involving daily monitoring of clinical data, education, and personal
      feedback proved to be most successful in realizing behavioral change and reducing
      costs. The benefits of videoconferencing were mainly related to its effects on
      socioeconomic factors such as education and cost reduction, but also on
      monitoring disease. Additionally, videoconferencing seemed to maintain quality of
      care while producing cost savings. CONCLUSIONS: The selected studies suggest that
      both teleconsultation and videoconferencing are practical, cost-effective, and
      reliable ways of delivering a worthwhile health care service to diabetics.
      However, the diversity in study design and reported findings makes a strong
      conclusion premature. To further the contribution of technology to diabetes care,
      interactive systems should be developed that integrate monitoring and
      personalized feedback functions.

PMID- 18093905
TI  - Spontaneous fluctuations in posterior alpha-band EEG activity reflect variability
      in excitability of human visual areas.
AB  - Neural activity fluctuates dynamically with time, and these changes have been
      reported to be of behavioral significance, despite occurring spontaneously.
      Through electroencephalography (EEG), fluctuations in alpha-band (8-14 Hz)
      activity have been identified over posterior sites that covary on a trial-by
      trial basis with whether an upcoming visual stimulus will be detected or not.
      These fluctuations are thought to index the momentary state of visual cortex
      excitability. Here, we tested this hypothesis by directly exciting human visual
      cortex via transcranial magnetic stimulation (TMS) to induce illusory visual
      percepts (phosphenes) in blindfolded participants, while simultaneously recording
      EEG. We found that identical TMS-stimuli evoked a percept (P-yes) or not (P-no)
      depending on prestimulus alpha-activity. Low prestimulus alpha-band power
      resulted in TMS reliably inducing phosphenes (P-yes trials), whereas high
      prestimulus alpha-values led the same TMS-stimuli failing to evoke a visual
      percept (P-no trials). Additional analyses indicated that the perceptually
      relevant fluctuations in alpha-activity/visual cortex excitability were spatially
      specific and occurred on a subsecond time scale in a recurrent pattern. Our data
      directly link momentary levels of posterior alpha-band activity to distinct
      states of visual cortex excitability, and suggest that their spontaneous
      fluctuation constitutes a visual operation mode that is activated automatically
      even without retinal input.

PMID- 18093907
TI  - Launching a ubiquitination cascade at DNA breaks.

PMID- 18093908
TI  - Controlling water transport through artificial polymer/protein hybrid membranes.

PMID- 18093909
TI  - Profile of Christopher Miller.

PMID- 18093910
TI  - New ideas on root hair growth appear from the flanks.

PMID- 18093911
TI  - An intragenic MEF2-dependent enhancer directs muscle-specific expression of
      microRNAs 1 and 133.
AB  - The muscle-specific microRNAs, miR-1 and miR-133, play important roles in muscle
      growth and differentiation. Here, we show that the MEF2 transcription factor, an
      essential regulator of muscle development, directly activates transcription of a
      bicistronic primary transcript encoding miR-1-2 and 133a-1 via an intragenic
      muscle-specific enhancer located between the miR-1-2 and 133a-1 coding regions.
      This MEF2-dependent enhancer is activated in the linear heart tube during mouse
      embryogenesis and thereafter controls transcription throughout the atrial and
      ventricular chambers of the heart. MEF2 together with MyoD also regulates the miR
      1-2/-133a-1 intragenic enhancer in the somite myotomes and in all skeletal muscle
      fibers during embryogenesis and adulthood. A similar muscle-specific intragenic
      enhancer controls transcription of the miR-1-1/-133a-2 locus. These findings
      reveal a common architecture of regulatory elements associated with the miR-1/
      133 genes and underscore the central role of MEF2 as a regulator of the
      transcriptional and posttranscriptional pathways that control cardiac and
      skeletal muscle development.

PMID- 18093912
TI  - Mutation of an A-kinase-anchoring protein causes long-QT syndrome.
AB  - A-kinase anchoring proteins (AKAPs) recruit signaling molecules and present them
      to downstream targets to achieve efficient spatial and temporal control of their
      phosphorylation state. In the heart, sympathetic nervous system (SNS) regulation
      of cardiac action potential duration (APD), mediated by beta-adrenergic receptor
      (betaAR) activation, requires assembly of AKAP9 (Yotiao) with the I(Ks) potassium
      channel alpha subunit (KCNQ1). KCNQ1 mutations that disrupt this complex cause
      type 1 long-QT syndrome (LQT1), one of the potentially lethal heritable
      arrhythmia syndromes. Here, we report identification of (i) regions on Yotiao
      critical to its binding to KCNQ1 and (ii) a single putative LQTS-causing mutation
      (S1570L) in AKAP9 (Yotiao) localized to the KCNQ1 binding domain in 1/50 (2%)
      subjects with a clinically robust phenotype for LQTS but absent in 1,320
      reference alleles. The inherited S1570L mutation reduces the interaction between
      KCNQ1 and Yotiao, reduces the cAMP-induced phosphorylation of the channel,
      eliminates the functional response of the I(Ks) channel to cAMP, and prolongs the
      action potential in a computational model of the ventricular cardiocyte. These
      reconstituted cellular consequences of the inherited S1570L-Yotiao mutation are
      consistent with delayed repolarization of the ventricular action potential
      observed in the affected siblings. Thus, we have demonstrated a link between
      genetic perturbations in AKAP and human disease in general and AKAP9 and LQTS in
      particular.

PMID- 18093913
TI  - Three-dimensional structure of cytoplasmic dynein bound to microtubules.
AB  - Cytoplasmic dynein is a large, microtubule-dependent molecular motor (1.2 MDa).
      Although the structure of dynein by itself has been characterized, its
      conformation in complex with microtubules is still unknown. Here, we used
      cryoelectron microscopy (cryo-EM) to visualize the interaction between dynein and
      microtubules. Most dynein molecules in the nucleotide-free state are bound to the
      microtubule in a defined conformation and orientation. A 3D image reconstruction
      revealed that dynein's head domain, formed by a ring-like arrangement of AAA+
      domains, is located approximately 280 A away from the center of the microtubule.
      The order of the AAA+ domains in the ring was determined by using recombinant
      markers. Furthermore, a 3D helical image reconstruction of microtubules with a
      dynein's microtubule binding domain [dynein stalk (DS)] revealed that the stalk
      extends perpendicular to the microtubule. By combining the 3D maps of the dynein
      microtubule and DS-microtubule complexes, we present a model for how dynein in
      the nucleotide-free state binds to microtubules and discuss models for dynein's
      power stroke.

PMID- 18093914
TI  - The subunit composition of hinokiresinol synthase controls geometrical
      selectivity in norlignan formation.
AB  - The selective formation of E- or Z-isomers is an important process in natural
      product metabolism. We show that the subunit composition of an enzyme can alter
      the geometrical composition of the enzymatic products. Hinokiresinol synthase,
      purified from Asparagus officinalis cell cultures, is responsible for the
      conversion of (7E,7'E)-4-coumaryl 4-coumarate to (Z)-hinokiresinol, the first
      step in norlignan formation. The protein is most likely a heterodimer composed of
      two distinct subunits, which share identity with members of the phloem protein 2
      gene superfamily. Interestingly, each recombinant subunit of hinokiresinol
      synthase expressed in Escherichia coli solely converted (7E,7'E)-4-coumaryl 4
      coumarate to the unnatural (E)-hinokiresinol, the E-isomer of (Z)-hinokiresinol.
      By contrast, a mixture of recombinant subunits catalyzed the formation of (Z)
      hinokiresinol from the same substrate.

PMID- 18093915
TI  - Durable effects of concentrated disadvantage on verbal ability among African
      American children.
AB  - Disparities in verbal ability, a major predictor of later life outcomes, have
      generated widespread debate, but few studies have been able to isolate
      neighborhood-level causes in a developmentally and ecologically appropriate way.
      This study presents longitudinal evidence from a large-scale study of >2,000
      children ages 6-12 living in Chicago, along with their caretakers, who were
      followed wherever they moved in the U.S. for up to 7 years. African-American
      children are exposed in such disproportionate numbers to concentrated
      disadvantage that white and Latino children cannot be reliably compared, calling
      into question traditional research strategies assuming common points of overlap
      in ecological risk. We therefore focus on trajectories of verbal ability among
      African-American children, extending recently developed counterfactual methods
      for time-varying causes and outcomes to adjust for a wide range of predictors of
      selection into and out of neighborhoods. The results indicate that living in a
      severely disadvantaged neighborhood reduces the later verbal ability of black
      children on average by approximately 4 points, a magnitude that rivals missing a
      year or more of schooling.

PMID- 18093916
TI  - Folding trajectories of human dihydrofolate reductase inside the GroEL GroES
      chaperonin cavity and free in solution.
AB  - The chaperonin GroEL binds non-native polypeptides in an open ring via
      hydrophobic contacts and then, after ATP and GroES binding to the same ring as
      polypeptide, mediates productive folding in the now hydrophilic, encapsulated cis
      chamber. The nature of the folding reaction in the cis cavity remains poorly
      understood. In particular, it is unclear whether polypeptides take the same route
      to the native state in this cavity as they do when folding spontaneously free in
      solution. Here, we have addressed this question by using NMR measurements of the
      time course of acquisition of amide proton exchange protection of human
      dihydrofolate reductase (DHFR) during folding in the presence of methotrexate and
      ATP either free in solution or inside the stable cavity formed between a single
      ring variant of GroEL, SR1, and GroES. Recovery of DHFR refolded by the SR1/GroES
      mediated reaction is 2-fold higher than in the spontaneous reaction.
      Nevertheless, DHFR folding was found to proceed by the same trajectories inside
      the cis folding chamber and free in solution. These observations are consistent
      with the description of the chaperonin chamber as an "Anfinsen cage" where
      polypeptide folding is determined solely by the amino acid sequence, as it is in
      solution. However, if misfolding occurs in the confinement of the chaperonin
      cavity, the polypeptide chain cannot undergo aggregation but rather finds its way
      back to a productive pathway in a manner that cannot be accomplished in solution,
      resulting in the observed high overall recovery.

PMID- 18093917
TI  - Endogenous circadian rhythm in human motor activity uncoupled from circadian
      influences on cardiac dynamics.
AB  - The endogenous circadian pacemaker influences key physiologic functions, such as
      body temperature and heart rate, and is normally synchronized with the sleep/wake
      cycle. Epidemiological studies demonstrate a 24-h pattern in adverse
      cardiovascular events with a peak at approximately 10 a.m. It is unknown whether
      this pattern in cardiac risk is caused by a day/night pattern of behaviors,
      including activity level and/or influences from the internal circadian pacemaker.
      We recently found that a scaling index of cardiac vulnerability has an endogenous
      circadian peak at the circadian phase corresponding to approximately 10 a.m.,
      which conceivably could contribute to the morning peak in cardiac risk. Here, we
      test whether this endogenous circadian influence on cardiac dynamics is caused by
      circadian-mediated changes in motor activity or whether activity and heart rate
      dynamics are decoupled across the circadian cycle. We analyze high-frequency
      recordings of motion from young healthy subjects during two complementary
      protocols that decouple the sleep/wake cycle from the circadian cycle while
      controlling scheduled behaviors. We find that static activity properties (mean
      and standard deviation) exhibit significant circadian rhythms with a peak at the
      circadian phase corresponding to 5-9 p.m. ( approximately 9 h later than the peak
      in the scale-invariant index of heartbeat fluctuations). In contrast, dynamic
      characteristics of the temporal scale-invariant organization of activity
      fluctuations (long-range correlations) do not exhibit a circadian rhythm. These
      findings suggest that endogenous circadian-mediated activity variations are not
      responsible for the endogenous circadian rhythm in the scale-invariant structure
      of heartbeat fluctuations and likely do not contribute to the increase in cardiac
      risk at approximately 10 a.m.

PMID- 18093918
TI  - An extended dynamical hydration shell around proteins.
AB  - The focus in protein folding has been very much on the protein backbone and
      sidechains. However, hydration waters make comparable contributions to the
      structure and energy of proteins. The coupling between fast hydration dynamics
      and protein dynamics is considered to play an important role in protein folding.
      Fundamental questions of protein hydration include, how far out into the solvent
      does the influence of the biomolecule reach, how is the water affected, and how
      are the properties of the hydration water influenced by the separation between
      protein molecules in solution? We show here that Terahertz spectroscopy directly
      probes such solvation dynamics around proteins, and determines the width of the
      dynamical hydration layer. We also investigate the dependence of solvation
      dynamics on protein concentration. We observe an unexpected nonmonotonic trend in
      the measured terahertz absorbance of the five helix bundle protein lambda(6-85)*
      as a function of the protein: water molar ratio. The trend can be explained by
      overlapping solvation layers around the proteins. Molecular dynamics simulations
      indicate water dynamics in the solvation layer around one protein to be distinct
      from bulk water out to approximately 10 A. At higher protein concentrations such
      that solvation layers overlap, the calculated absorption spectrum varies
      nonmonotonically, qualitatively consistent with the experimental observations.
      The experimental data suggest an influence on the correlated water network motion
      beyond 20 A, greater than the pure structural correlation length usually
      observed.

PMID- 18093919
TI  - Therapeutic B cell depletion impairs adaptive and autoreactive CD4+ T cell
      activation in mice.
AB  - CD20 antibody depletion of B lymphocytes effectively ameliorates multiple T cell
      mediated autoimmune diseases through mechanisms that remain unclear. To address
      this, a mouse CD20 antibody that depletes >95% of mature B cells in mice with
      otherwise intact immune systems was used to assess the role of B cells in CD4(+)
      and CD8(+) T cell activation and expansion in vivo. B cell depletion had no
      direct effect on T cell subsets or the activation status of CD4(+) and CD8(+) T
      cells in naive mice. However, B cell depletion impaired CD4(+) T cell activation
      and clonal expansion in response to protein antigens and pathogen challenge,
      whereas CD8(+) T cell activation was not affected. In vivo dendritic cell
      ablation, along with CD20 immunotherapy, revealed that optimal antigen-specific
      CD4(+) T cell priming required both B cells and dendritic cells. Most
      importantly, B cell depletion inhibited antigen-specific CD4(+) T cell expansion
      in both collagen-induced arthritis and autoimmune diabetes mouse models. These
      results provide direct evidence that B cells contribute to T cell activation and
      expansion in vivo and offer insights into the mechanism of action for B cell
      depletion therapy in the treatment of autoimmunity.

PMID- 18093920
TI  - Transmembrane domains of the syndecan family of growth factor coreceptors display
      a hierarchy of homotypic and heterotypic interactions.
AB  - The single-pass transmembrane domains (TMDs) of the syndecan family of cell
      surface adhesion molecules have been implicated in functional protein-protein
      interactions. Although each paralog contains a conserved GxxxG dimerization
      motif, we show here that the syndecan-1 TMD dimerizes weakly, the syndecan-3 and
      syndecan-4 TMDs each dimerize strongly, and the syndecan-2 TMD dimerizes very
      strongly. These markedly different levels of self-association suggest that
      paralog TMDs play different roles in directing functional interactions of each
      full-length syndecan family member. We further show that each syndecan TMD forms
      detergent-resistant heteromeric complexes with other paralogs, and that these
      interactions exhibit selectivity. Although heteromeric interactions among full
      length syndecan paralogs have not been reported, we argue that the distinct
      hierarchy of protein-protein interactions mediated by the syndecan TMDs may give
      rise to considerable complexity in syndecan function. The demonstration that TMD
      homodimerization and heterodimerization can be mediated by GxxxG motifs and
      modulated by sequence context has implications for the signaling mechanisms of
      other cell surface receptors, including the integrins and the erbB family.

PMID- 18093921
TI  - Selection of mammalian cells based on their cell-cycle phase using
      dielectrophoresis.
AB  - An effective, noninvasive means of selecting cells based on their phase within
      the cell cycle is an important capability for biological research. Current
      methods of producing synchronous cell populations, however, tend to disrupt the
      natural physiology of the cell or suffer from low synchronization yields. In this
      work, we report a microfluidic device that utilizes the dielectrophoresis
      phenomenon to synchronize cells by exploiting the relationship between the cell's
      volume and its phase in the cell cycle. The dielectrophoresis activated cell
      synchronizer (DACSync) device accepts an asynchronous mixture of cells at the
      inlet, fractionates the cell populations according to the cell-cycle phase
      (G(1)/S and G(2)/M), and elutes them through different outlets. The device is
      gentle and efficient; it utilizes electric fields that are 1-2 orders of
      magnitude below those used in electroporation and enriches asynchronous tumor
      cells in the G(1) phase to 96% in one round of sorting, in a continuous flow
      manner at a throughput of 2 x 10(5) cells per hour per microchannel. This work
      illustrates the feasibility of using laminar flow and electrokinetic forces for
      the efficient, noninvasive separation of living cells.

PMID- 18093922
TI  - A synthetic precedent for the [FeIV2(mu-O)2] diamond core proposed for methane
      monooxygenase intermediate Q.
AB  - Intermediate Q, the methane-oxidizing species of soluble methane monooxygenase,
      is proposed to have an [Fe(IV)(2)(mu-O)(2)] diamond core. In an effort to obtain
      a synthetic precedent for such a core, bulk electrolysis at 900 mV (versus
      Fc(+/0)) has been performed in MeCN at -40 degrees C on a valence-delocalized
      [Fe(III)Fe(IV)(mu-O)(2)(L(b))(2)](3+) complex (1b) (E(1/2) = 760 mV versus
      Fc(+/0)). Oxidation of 1b results in the near-quantitative formation of a deep
      red complex, designated 2b, that exhibits a visible spectrum with lambda(max) at
      485 nm (9,800 M(-1).cm(-1)) and 875 nm (2,200 M(-1).cm(-1)). The 4.2 K Mossbauer
      spectrum of 2b exhibits a quadrupole doublet with delta = -0.04(1) mm.s(-1) and
      DeltaE(Q) = 2.09(2) mm.s(-1), parameters typical of an iron(IV) center. The
      Mossbauer patterns observed in strong applied fields show that 2b is an
      antiferromagnetically coupled diiron(IV) center. Resonance Raman studies reveal
      the diagnostic vibration mode of the [Fe(2)(mu-O)(2)] core at 674 cm(-1),
      downshifting 30 cm(-1) upon (18)O labeling. Extended x-ray absorption fine
      structure (EXAFS) analysis shows two O/N scatterers at 1.78 A and an Fe scatterer
      at 2.73 A. Based on the accumulated spectroscopic evidence, 2b thus can be
      formulated as [Fe(IV)(2)(mu-O)(2)(L(b))(2)](4+), the first synthetic complex with
      an [Fe(IV)(2)(mu-O)(2)] core. A comparison of 2b and its mononuclear analog
      [Fe(IV)(O)(L(b))(NCMe)](2+) (4b) reveals that 4b is 100-fold more reactive than
      2b in oxidizing weak C H bonds. This surprising observation may shed further
      light on how intermediate Q carries out the hydroxylation of methane.

PMID- 18093923
TI  - A potent cytotoxic photoactivated platinum complex.
AB  - We show by x-ray crystallography that the complex trans, trans, trans
      [Pt(N(3))(2)(OH)(2)(NH(3))(py)] (1) contains an octahedral Pt(IV) center with
      almost linear azido ligands. Complex 1 is remarkably stable in the dark, even in
      the presence of cellular reducing agents such as glutathione, but readily
      undergoes photoinduced ligand substitution and photoreduction reactions. When 1
      is photoactivated in cells, it is highly toxic: 13-80 x more cytotoxic than the
      Pt(II) anticancer drug cisplatin, and ca. 15 x more cytotoxic toward cisplatin
      resistant human ovarian cancer cells. Cisplatin targets DNA, and DNA platination
      levels induced in HaCaT skin cells by 1 were similar to those of cisplatin.
      However, cisplatin forms mainly intrastrand cis diguanine cross-links on DNA
      between neighboring nucleotides, whereas photoactivated complex 1 rapidly forms
      unusual trans azido/guanine, and then trans diguanine Pt(II) adducts, which are
      probably mainly intrastrand cross-links between two guanines separated by a third
      base. DNA interstrand and DNA-protein cross-links were also detected.
      Importantly, DNA repair synthesis on plasmid DNA platinated by photoactivated 1
      was markedly lower than for cisplatin or its isomer transplatin (an inactive
      complex). Single-cell electrophoresis experiments also demonstrated that the DNA
      damage is different from that induced by cisplatin or transplatin. Cell death is
      not solely dependent on activation of the caspase 3 pathway, and, in contrast to
      cisplatin, p53 protein did not accumulate in cells after photosensitization of 1.
      The trans diazido Pt(IV) complex 1 therefore has remarkable properties and is a
      candidate for use in photoactivated cancer chemotherapy.

PMID- 18093924
TI  - Evidence for a vascular contribution to diffusion FMRI at high b value.
AB  - Recent work has suggested that diffusion-weighted functional magnetic resonance
      imaging (FMRI) with strong diffusion weighting (high b value) detects neuronal
      swelling that is directly related to neuronal firing. This would constitute a
      much more direct measure of brain activity than current methods and represent a
      major advance in neuroimaging. However, it has not been firmly established that
      the observed signal changes do not reflect residual vascular effects, which are
      known to exist at low b value. This study measures the vascular component of
      diffusion FMRI directly by using hypercapnia, which induces blood flow changes in
      the absence of a change in neuronal firing. Hypercapnia elicits a similar
      diffusion FMRI response to a visual stimulus including a rise in percent signal
      change with increasing b value, which was reported for visual activation.
      Analysis of the response timing found no evidence for an early response at high b
      value, which has been reported as evidence for a nonhemodynamic response. These
      results suggest that a large component of the diffusion FMRI signal at high b
      value is vascular rather than neuronal.

PMID- 18093925
TI  - Trophic ecology of invasive Argentine ants in their native and introduced ranges.
AB  - Although the ecological effects of invasions often become obvious soon after
      introduced species become established, more gradual effects may take years to
      manifest and can thus require long-term data for quantification. We analyzed an 8
      year record of stable isotope data on Argentine ants (Linepithema humile) from
      southern California to infer how the trophic position of this widespread invasive
      species changes over time as native ant species are displaced. We couple this
      longitudinal analysis with a biregional comparison of stable isotope data
      (delta(15)N) on ants from Argentina (native range) and California (introduced
      range) to quantify (i) how the trophic position of L. humile differs between
      native and introduced populations, and (ii) how relative trophic position as
      estimated by delta(15)N values of Argentine ants compare with those of other ants
      at the same site. Both long-term and biregional comparisons indicate that the
      Argentine ant's relative trophic position is reduced at sites with a longer
      history of occupation. Over the course of 8 years, the relative trophic position
      of L. humile remained high at the leading edge of an invasion front but declined,
      on average, behind the front as native ants disappeared. Relative to native
      populations, where L. humile is among the most carnivorous of ants, Argentine
      ants from California occupied lower trophic positions. These results support the
      hypothesis that Argentine ants shift their diet after establishment as a result
      of resource depletion and increasing reliance on plant-based resources,
      especially honeydew-producing Hemiptera. Our results demonstrate the value of
      long-term and biregional data in uncovering ecological effects of invasions.

PMID- 18093927
TI  - Combinatorics of feedback in cellular uptake and metabolism of small molecules.
AB  - We analyze the connection between structure and function for regulatory motifs
      associated with cellular uptake and usage of small molecules. Based on the
      boolean logic of the feedback we suggest four classes: the socialist, consumer,
      fashion, and collector motifs. We find that the socialist motif is good for
      homeostasis of a useful but potentially poisonous molecule, whereas the consumer
      motif is optimal for nutrition molecules. Accordingly, examples of these motifs
      are found in, respectively, the iron homeostasis system in various organisms and
      in the uptake of sugar molecules in bacteria. The remaining two motifs have no
      obvious analogs in small molecule regulation, but we illustrate their behavior
      using analogies to fashion and obesity. These extreme motifs could inspire
      construction of synthetic systems that exhibit bistable, history-dependent
      states, and homeostasis of flux (rather than concentration).

PMID- 18093926
TI  - A synthetic host-guest system achieves avidin-biotin affinity by overcoming
      enthalpy-entropy compensation.
AB  - The molecular host cucurbit[7]uril forms an extremely stable inclusion complex
      with the dicationic ferrocene derivative bis(trimethylammoniomethyl)ferrocene in
      aqueous solution. The equilibrium association constant for this host-guest pair
      is 3 x 10(15) M(-1) (K(d) = 3 x 10(-16) M), equivalent to that exhibited by the
      avidin-biotin pair. Although purely synthetic systems with larger association
      constants have been reported, the present one is unique because it does not rely
      on polyvalency. Instead, it achieves its extreme affinity by overcoming the
      compensatory enthalpy-entropy relationship usually observed in supramolecular
      complexes. Its disproportionately low entropic cost is traced to extensive host
      desolvation and to the rigidity of both the host and the guest.

PMID- 18093928
TI  - Agent-based modeling of deforestation in southern Yucatan, Mexico, and
      reforestation in the Midwest United States.
AB  - We combine mixed-methods research with integrated agent-based modeling to
      understand land change and economic decision making in the United States and
      Mexico. This work demonstrates how sustainability science benefits from combining
      integrated agent-based modeling (which blends methods from the social,
      ecological, and information sciences) and mixed-methods research (which
      interleaves multiple approaches ranging from qualitative field research to
      quantitative laboratory experiments and interpretation of remotely sensed
      imagery). We test assumptions of utility-maximizing behavior in household-level
      landscape management in south-central Indiana, linking parcel data, land cover
      derived from aerial photography, and findings from laboratory experiments. We
      examine the role of uncertainty and limited information, preferences,
      differential demographic attributes, and past experience and future time
      horizons. We also use evolutionary programming to represent bounded rationality
      in agriculturalist households in the southern Yucatan of Mexico. This approach
      captures realistic rule of thumb strategies while identifying social and
      environmental factors in a manner similar to econometric models. These case
      studies highlight the role of computational models of decision making in land
      change contexts and advance our understanding of decision making in general.

PMID- 18093929
TI  - Arabidopsis CBF1 and CBF3 have a different function than CBF2 in cold acclimation
      and define different gene classes in the CBF regulon.
AB  - The C-repeat-binding factor (CBF)/dehydration-responsive element-binding factor
      (DREB1) proteins constitute a small family of Arabidopsis transcriptional
      activators (CBF1/DREB1B, CBF2/DREB1C, and CBF3/DREB1A) that play a prominent role
      in cold acclimation. A fundamental question about these factors that remains to
      be answered is whether they are functionally equivalent. Recently, we reported
      that CBF2 negatively regulates CBF1 and CBF3 expression, and that CBFs are
      subjected to different temporal regulation during cold acclimation, which
      suggested this might not be the case. In this study, we have analyzed the
      expression of CBF genes in different tissues of Arabidopsis, during development
      and in response to low temperature, and characterized RNA interference (RNAi) and
      antisense lines that fail to accumulate CBF1 or/and CBF3 mRNAs under cold
      conditions. We found that CBF1 and CBF3 are regulated in a different way than
      CBF2. Moreover, in contrast to CBF2, CBF1 and CBF3 are not involved in regulating
      other CBF genes and positively regulate cold acclimation by activating the same
      subset of CBF-target genes. All these results demonstrate that CBF1 and CBF3 have
      different functions than CBF2. We also found that the CBF regulon is composed of
      at least two different kind of genes, one of them requiring the simultaneous
      expression of both CBF1 and CBF3 to be properly induced. This indicates that CBF1
      and CBF3 have a concerted additive effect to induce the whole CBF regulon and the
      complete development of cold acclimation.

PMID- 18093930
TI  - The evolution of urban sprawl: evidence of spatial heterogeneity and increasing
      land fragmentation.
AB  - We investigate the dynamics and spatial distribution of land use fragmentation in
      a rapidly urbanizing region of the United States to test key propositions
      regarding the evolution of sprawl. Using selected pattern metrics and data from
      1973 and 2000 for the state of Maryland, we find significant increases in
      developed and undeveloped land fragmentation but substantial spatial
      heterogeneity as well. Estimated fragmentation gradients that describe mean
      fragmentation as a function of distance from urban centers confirm the hypotheses
      that fragmentation rises and falls with distance and that the point of maximum
      fragmentation shifted outward over time. However, rather than outward increases
      in sprawl balanced by development infill, we find substantial and significant
      increases in mean fragmentation values along the entire urban-rural gradient.
      These findings are in contrast to the results of Burchfield et al. [Burchfield M,
      Overman HG, Puga D, Turner MA (2006) Q J Econ 121:587-633], who conclude that the
      extent of sprawl remained roughly unchanged in the Unites States between 1976 and
      1992. As demonstrated here, both the data and pattern measure used in their study
      are systematically biased against recording low-density residential development,
      the very land use that we find is most strongly associated with fragmentation.
      Other results demonstrate the association between exurban growth and increasing
      fragmentation and the systematic variation of fragmentation with nonurban
      factors. In particular, proximity to the Chesapeake Bay is negatively associated
      with fragmentation, suggesting that an attraction effect associated with this
      natural amenity has concentrated development.

PMID- 18093931
TI  - Ecological feedbacks following deforestation create the potential for a
      catastrophic ecosystem shift in tropical dry forest.
AB  - The long-term ecological response to recurrent deforestation associated with
      shifting cultivation remains poorly investigated, especially in the dry tropics.
      We present a study of phosphorus (P) dynamics in the southern Yucatan,
      highlighting the possibility of abrupt shifts in biogeochemical cycling resulting
      from positive feedbacks between vegetation and its limiting resources. After
      three cultivation-fallow cycles, available soil P declines by 44%, and one-time P
      inputs from biomass burning decline by 76% from mature forest levels.
      Interception of dust-borne P ("canopy trapping") declines with lower plant
      biomass and leaf area, limiting deposition in secondary forest. Potential
      leaching losses are greater in secondary than in mature forest, but the
      difference is very small compared with the difference in P inputs. The decline in
      new P from atmospheric deposition creates a long-term negative ecosystem balance
      for phosphorus. The reduction in soil P availability will feed back to further
      limit biomass recovery and may induce a shift to sparser vegetation. Degradation
      induced by hydrological and biogeochemical feedbacks on P cycling under shifting
      cultivation will affect farmers in the near future. Without financial support to
      encourage the use of fertilizer, farmers could increase the fallow period, clear
      new land, or abandon agriculture for off-farm employment. Their response will
      determine the regional balance between forest loss and forest regrowth, as well
      as the frequency of use and rate of recovery at a local scale, further feeding
      back on ecological processes at multiple scales.

PMID- 18093932
TI  - Learning from episodes of degradation and recovery in variable Australian
      rangelands.
AB  - Land-change science emphasizes the intimate linkages between the human and
      environmental components of land management systems. Recent theoretical
      developments in drylands identify a small set of key principles that can guide
      the understanding of these linkages. Using these principles, a detailed study of
      seven major degradation episodes over the past century in Australian grazed
      rangelands was reanalyzed to show a common set of events: (i) good climatic and
      economic conditions for a period, leading to local and regional social responses
      of increasing stocking rates, setting the preconditions for rapid environmental
      collapse, followed by (ii) a major drought coupled with a fall in the market
      making destocking financially unattractive, further exacerbating the pressure on
      the environment; then (iii) permanent or temporary declines in grazing
      productivity, depending on follow-up seasons coupled again with market and social
      conditions. The analysis supports recent theoretical developments but shows that
      the establishment of environmental knowledge that is strictly local may be
      insufficient on its own for sustainable management. Learning systems based in a
      wider community are needed that combine local knowledge, formal research, and
      institutional support. It also illustrates how natural variability in the state
      of both ecological and social systems can interact to precipitate nonequilibrial
      change in each other, so that planning cannot be based only on average
      conditions. Indeed, it is this variability in both environment and social
      subsystems that hinders the local learning required to prevent collapse.

PMID- 18093933
TI  - Incorporating plant functional diversity effects in ecosystem service
      assessments.
AB  - Global environmental change affects the sustained provision of a wide set of
      ecosystem services. Although the delivery of ecosystem services is strongly
      affected by abiotic drivers and direct land use effects, it is also modulated by
      the functional diversity of biological communities (the value, range, and
      relative abundance of functional traits in a given ecosystem). The focus of this
      article is on integrating the different possible mechanisms by which functional
      diversity affects ecosystem properties that are directly relevant to ecosystem
      services. We propose a systematic way for progressing in understanding how land
      cover change affects these ecosystem properties through functional diversity
      modifications. Models on links between ecosystem properties and the local mean,
      range, and distribution of plant trait values are numerous, but they have been
      scattered in the literature, with varying degrees of empirical support and
      varying functional diversity components analyzed. Here we articulate these
      different components in a single conceptual and methodological framework that
      allows testing them in combination. We illustrate our approach with examples from
      the literature and apply the proposed framework to a grassland system in the
      central French Alps in which functional diversity, by responding to land use
      change, alters the provision of ecosystem services important to local
      stakeholders. We claim that our framework contributes to opening a new area of
      research at the interface of land change science and fundamental ecology.

PMID- 18093934
TI  - The emergence of land change science for global environmental change and
      sustainability.
AB  - Land change science has emerged as a fundamental component of global
      environmental change and sustainability research. This interdisciplinary field
      seeks to understand the dynamics of land cover and land use as a coupled human
      environment system to address theory, concepts, models, and applications relevant
      to environmental and societal problems, including the intersection of the two.
      The major components and advances in land change are addressed: observation and
      monitoring; understanding the coupled system-causes, impacts, and consequences;
      modeling; and synthesis issues. The six articles of the special feature are
      introduced and situated within these components of study.

PMID- 18093935
TI  - Axis-dependent anisotropy in protein unfolding from integrated nonequilibrium
      single-molecule experiments, analysis, and simulation.
AB  - We present a comprehensive study that integrates experimental and theoretical
      nonequilibrium techniques to map energy landscapes along well defined pull-axis
      specific coordinates to elucidate mechanisms of protein unfolding. Single
      molecule force-extension experiments along two different axes of photoactive
      yellow protein combined with nonequilibrium statistical mechanical analysis and
      atomistic simulation reveal energetic and mechanistic anisotropy. Steered
      molecular dynamics simulations and free-energy curves constructed from the
      experimental results reveal that unfolding along one axis exhibits a transition
      state-like feature where six hydrogen bonds break simultaneously with weak
      interactions observed during further unfolding. The other axis exhibits a
      constant (unpeaked) force profile indicative of a noncooperative transition, with
      enthalpic (e.g., H-bond) interactions being broken throughout the unfolding
      process. Striking qualitative agreement was found between the force-extension
      curves derived from steered molecular dynamics calculations and the equilibrium
      free-energy curves obtained by Jarzynski-Hummer-Szabo analysis of the
      nonequilibrium work data. The anisotropy persists beyond pulling distances of
      more than twice the initial dimensions of the folded protein, indicating a rich
      energy landscape to the mechanically fully unfolded state. Our findings challenge
      the notion that cooperative unfolding is a universal feature in protein
      stability.

PMID- 18093936
TI  - Synthetic iron-oxo "diamond core" mimics structure of key intermediate in methane
      monooxygenase catalytic cycle.

PMID- 18093937
TI  - The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet
      junctions and is important for droplet morphology.
AB  - Lipodystrophy is a disorder characterized by a loss of adipose tissue often
      accompanied by severe hypertriglyceridemia, insulin resistance, diabetes, and
      fatty liver. It can be inherited or acquired. The most severe inherited form is
      Berardinelli-Seip Congenital Lipodystrophy Type 2, associated with mutations in
      the BSCL2 gene. BSCL2 encodes seipin, the function of which has been entirely
      unknown. We now report the identification of yeast BSCL2/seipin through a screen
      to detect genes important for lipid droplet morphology. The absence of yeast
      seipin results in irregular lipid droplets often clustered alongside proliferated
      endoplasmic reticulum (ER); giant lipid droplets are also seen. Many small
      irregular lipid droplets are also apparent in fibroblasts from a BSCL2 patient.
      Human seipin can functionally replace yeast seipin, but a missense mutation in
      human seipin that causes lipodystrophy, or corresponding mutations in the yeast
      gene, render them unable to complement. Yeast seipin is localized in the ER,
      where it forms puncta. Almost all lipid droplets appear to be on the ER, and
      seipin is found at these junctions. Therefore, we hypothesize that seipin is
      important for droplet maintenance and perhaps assembly. In addition to detecting
      seipin, the screen identified 58 other genes whose deletions cause aberrant lipid
      droplets, including 2 genes encoding proteins known to activate lipin, a
      lipodystrophy locus in mice, and 16 other genes that are involved in endosomal
      lysosomal trafficking. The genes identified in our screen should be of value in
      understanding the pathway of lipid droplet biogenesis and maintenance and the
      cause of some lipodystrophies.

PMID- 18093938
TI  - Resolving the problem of persistence in the switch from acute to chronic
      inflammation.

PMID- 18093939
TI  - Site-directed, virus-free, and inducible RNAi in embryonic stem cells.
AB  - RNAi is a powerful tool for interrogating gene function in ES cells. Combining
      the high penetrance of a microRNA-embedded shRNA (shRNA-mir) cassette with a
      locus-defined, inducible expression strategy, we developed a system for RNAi in
      mouse ES cells. An shRNA-mir cassette is targeted near the constitutively active
      HPRT locus under a tetracycline (tet)-regulatable promoter through Cre-mediated
      site-specific recombination. The major advantage of this system is that the shRNA
      mir cassette can be targeted to a precise locus, allowing for control of shRNA
      mir expression in an inducible fashion. Induction of an shRNA-mir directed
      against the pluripotency factor, Nanog, resulted in the loss of self-renewal and
      differentiation to parietal endoderm-like cells, which can be rescued by the
      introduction of an RNAi-immune version of Nanog cDNA. Knockdown efficiency can be
      enhanced by using multiple shRNA-mir hairpins against the target gene, which was
      further validated by knocking down two additional ES cell factors. This site
      directed, virus-free, and tet-inducible RNAi system, designated as SDVFi RNAi in
      our study, presents an efficient option for controlled gene silencing in ES
      cells.

PMID- 18093940
TI  - Circulating tumor antigen-specific regulatory T cells in patients with metastatic
      melanoma.
AB  - Although it is accepted that regulatory T cells (T regs) contribute to cancer
      progression, most studies in the field consider nonantigen-specific suppression.
      Here, we show the presence of tumor antigen-specific CD4(+) T regs in the blood
      of patients with metastatic melanoma. These CD4(+) T regs recognize a broad range
      of tumor antigens, including gp100 and TRP1 (melanoma tissue differentiation
      antigens), NY-ESO-1 (cancer/testis antigen) and survivin (inhibitor of apoptosis
      protein (IAP) family antigen). These tumor antigen-specific T regs proliferate in
      peripheral blood mononuclear cells (PBMC) cultures in response to specific 15-mer
      peptides, produce preferentially IL-10 and express high levels of FoxP3. They
      suppress autologous CD4(+)CD25(-) T cell responses in a cell contact-dependent
      manner and thus share properties of both naturally occurring regulatory T cells
      and type 1 regulatory T cells. Such tumor antigen-specific T regs were not
      detected in healthy individuals. These tumor antigen-specific T regs might thus
      represent another target for immunotherapy of metastatic melanoma.

PMID- 18093941
TI  - EPLIN mediates linkage of the cadherin catenin complex to F-actin and stabilizes
      the circumferential actin belt.
AB  - The cadherin-catenin complex is the major machinery for cell-cell adhesion in
      many animal species. This complex in general associates with actin fibers at its
      cytoplasmic side, organizing the adherens junction (AJ). In epithelial cells, the
      AJ encircles the cells near their apical surface and forms the "zonula adherens"
      or "adhesion belt." The mechanism as to how the cadherin-catenin complex and F
      actin cooperate to generate these junctional structures, however, remains
      unknown. Here, we show that EPLIN (epithelial protein lost in neoplasm; also
      known as Lima-1), an actin-binding protein, couples with alpha-catenin and, in
      turn, links the cadherin-catenin complex to F-actin. Without EPLIN, this linkage
      was unable to form. When EPLIN had been depleted in epithelial cells, the
      adhesion belt was disorganized and converted into zipper-like junctions in which
      actin fibers were radially arranged. However, nonjunctional actin fibers were not
      particularly affected by EPLIN depletion. As EPLIN is known to have the ability
      to suppress actin depolymerization, our results suggest that EPLIN functions to
      link the cadherin-catenin complex to F-actin and simultaneously stabilizes this
      population of actin fibers, resulting in the establishment of the adhesion belt.

PMID- 18093942
TI  - Profile of George Schatz.

PMID- 18093943
TI  - MET amplification occurs with or without T790M mutations in EGFR mutant lung
      tumors with acquired resistance to gefitinib or erlotinib.
AB  - In human lung adenocarcinomas harboring EGFR mutations, a second-site point
      mutation that substitutes methionine for threonine at position 790 (T790M) is
      associated with approximately half of cases of acquired resistance to the EGFR
      kinase inhibitors, gefitinib and erlotinib. To identify other potential
      mechanisms that contribute to disease progression, we used array-based
      comparative genomic hybridization (aCGH) to compare genomic profiles of EGFR
      mutant tumors from untreated patients with those from patients with acquired
      resistance. Among three loci demonstrating recurrent copy number alterations
      (CNAs) specific to the acquired resistance set, one contained the MET proto
      oncogene. Collectively, analysis of tumor samples from multiple independent
      patient cohorts revealed that MET was amplified in tumors from 9 of 43 (21%)
      patients with acquired resistance but in only two tumors from 62 untreated
      patients (3%) (P = 0.007, Fisher's Exact test). Among 10 resistant tumors from
      the nine patients with MET amplification, 4 also harbored the EGFR(T790M)
      mutation. We also found that an existing EGFR mutant lung adenocarcinoma cell
      line, NCI-H820, harbors MET amplification in addition to a drug-sensitive EGFR
      mutation and the T790M change. Growth inhibition studies demonstrate that these
      cells are resistant to both erlotinib and an irreversible EGFR inhibitor (CL
      387,785) but sensitive to a multikinase inhibitor (XL880) with potent activity
      against MET. Taken together, these data suggest that MET amplification occurs
      independently of EGFR(T790M) mutations and that MET may be a clinically relevant
      therapeutic target for some patients with acquired resistance to gefitinib or
      erlotinib.

PMID- 18093944
TI  - Nck adaptor proteins control the organization of neuronal circuits important for
      walking.
AB  - The intracellular signaling targets used by mammalian axon guidance receptors to
      organize the nervous system in vivo are unclear. The Nck1 and Nck2 SH2/SH3
      adaptors (collectively Nck) can couple phosphotyrosine (pTyr) signals to
      reorganization of the actin cytoskeleton and are therefore candidates for linking
      guidance cues to the regulatory machinery of the cytoskeleton. We find that
      selective inactivation of Nck in the murine nervous system causes a hopping gait
      and a defect in the spinal central pattern generator, which is characterized by
      synchronous firing of bilateral ventral motor neurons. Nck-deficient mice also
      show abnormal projections of corticospinal tract axons and defective development
      of the posterior tract of the anterior commissure. These phenotypes are
      consistent with a role for Nck in signaling initiated by different classes of
      guidance receptors, including the EphA4 receptor tyrosine kinase. Our data
      indicate that Nck adaptors couple pTyr guidance signals to cytoskeletal events
      required for the ipsilateral projections of spinal cord neurons and thus for
      normal limb movement.

PMID- 18093946
TI  - Embryonic stem cell-derived tissues are immunogenic but their inherent immune
      privilege promotes the induction of tolerance.
AB  - Although human embryonic stem (ES) cells may one day provide a renewable source
      of tissues for cell replacement therapy (CRT), histoincompatibility remains a
      significant barrier to their clinical application. Current estimates suggest that
      surprisingly few cell lines may be required to facilitate rudimentary tissue
      matching. Nevertheless, the degree of disparity between donor and recipient that
      may prove acceptable, and the extent of matching that is therefore required,
      remain unknown. To address this issue using a mouse model of CRT, we have derived
      a panel of ES cell lines that differ from CBA/Ca recipients at defined genetic
      loci. Here, we show that even expression of minor histocompatibility (mH)
      antigens is sufficient to provoke acute rejection of tissues differentiated from
      ES cells. Nevertheless, despite their immunogenicity in vivo, transplantation
      tolerance may be readily established by using minimal host conditioning with
      nondepleting monoclonal antibodies specific for the T cell coreceptors, CD4 and
      CD8. This propensity for tolerance could be attributed to the paucity of
      professional antigen-presenting cells and the expression of transforming growth
      factor (TGF)-beta(2). Together, these factors contribute to a state of acquired
      immune privilege that favors the polarization of infiltrating T cells toward a
      regulatory phenotype. Although the natural privileged status of ES cell-derived
      tissues is, therefore, insufficient to overcome even mH barriers, our findings
      suggest it may be harnessed effectively for the induction of dominant tolerance
      with minimal therapeutic intervention.

PMID- 18093945
TI  - Identification of H2N3 influenza A viruses from swine in the United States.
AB  - Although viruses of each of the 16 influenza A HA subtypes are potential human
      pathogens, only viruses of the H1, H2, and H3 subtype are known to have been
      successfully established in humans. H2 influenza viruses have been absent from
      human circulation since 1968, and as such they pose a substantial human pandemic
      risk. In this report, we isolate and characterize genetically similar avian/swine
      virus reassortant H2N3 influenza A viruses isolated from diseased swine from two
      farms in the United States. These viruses contained leucine at position 226 of
      the H2 protein, which has been associated with increased binding affinity to the
      mammalian alpha2,6Gal-linked sialic acid virus receptor. Correspondingly, the
      H2N3 viruses were able to cause disease in experimentally infected swine and mice
      without prior adaptation. In addition, the swine H2N3 virus was infectious and
      highly transmissible in swine and ferrets. Taken together, these findings suggest
      that the H2N3 virus has undergone some adaptation to the mammalian host and that
      their spread should be very closely monitored.

PMID- 18093947
TI  - Could genetic diversity in eastern North Pacific gray whales reflect global
      historic abundance?

PMID- 18093948
TI  - Universal scaling law of electrical turbulence in the mammalian heart.
AB  - Many biological processes, such as metabolic rate and life span, scale with body
      mass (BM) according to the universal law of allometric scaling: Y = aBM(b) (Y,
      biological process; b, scaling exponent). We investigated whether the temporal
      properties of ventricular fibrillation (VF), the major cause of sudden and
      unexpected cardiac death, scale with BM. By using high-resolution optical
      mapping, numerical simulations and metaanalysis of VF data in 11 mammalian
      species, we demonstrate that the interbeat interval of VF scales as VF(cycle)
      (length) = 53 x BM(1/4), spanning more than four orders of magnitude in BM from
      mouse to horse.

PMID- 18093949
TI  - Global topological dominance in the left hemisphere.
AB  - A series of experiments with right-handers demonstrated that the left hemisphere
      (LH) is reliably and consistently superior to the right hemisphere (RH) for
      global topological perception. These experiments generalized the topological
      account of lateralization to different kinds of topological properties (including
      holes, inside/outside relation, and "presence vs. absence") in comparison with a
      broad spectrum of geometric properties, including orientation, distance, size,
      mirror-symmetry, parallelism, collinearity, etc. The stimuli and paradigms used
      were also designed to prevent subjects from using various nontopological
      properties in performing the tasks of topological discrimination. Furthermore,
      task factors commonly considered in the study of hemispheric asymmetry, such as
      response latency vs. accuracy, vertical vs. horizontal presentation, detection
      vs. recognition, and simultaneous vs. sequential judgment, were manipulated to
      not be confounding factors. Moreover, left-handed subjects were tested and showed
      the right lateralization of topological perception, in the opposite direction of
      lateralization compared with right-handers. In addition, the functional magnetic
      resonance imaging measure revealed that only a region in the left temporal gyrus
      was consistently more activated across subjects in the task of topological
      discrimination, consistent with the behavioral results. In summary, the global
      topological dominance in the LH is well supported by the converging evidence from
      the variety of paradigms and techniques, and it suggests a unified solution to
      the current major controversies on visual lateralization.

PMID- 18093950
TI  - Chemical mimicry of viral capsid self-assembly.
AB  - Stable structures of icosahedral symmetry can serve numerous functional roles,
      including chemical microencapsulation and delivery of drugs and biomolecules,
      epitope presentation to allow for an efficient immunization process, synthesis of
      nanoparticles of uniform size, observation of encapsulated reactive
      intermediates, formation of structural elements for supramolecular constructs,
      and molecular computing. By examining physical models of spherical virus assembly
      we have arrived at a general synthetic strategy for producing chemical capsids at
      size scales between fullerenes and spherical viruses. Such capsids can be formed
      by self-assembly from a class of molecules developed from a symmetric pentagonal
      core. By designing chemical complementarity into the five interface edges of the
      molecule, we can produce self-assembling stable structures of icosahedral
      symmetry. We considered three different binding mechanisms: hydrogen bonding,
      metal binding, and formation of disulfide bonds. These structures can be designed
      to assemble and disassemble under controlled environmental conditions. We have
      conducted molecular dynamics simulation on a class of corannulene-based molecules
      to demonstrate the characteristics of self-assembly and to aid in the design of
      the molecular subunits. The edge complementarities can be of diverse structure,
      and they need not reflect the fivefold symmetry of the molecular core. Thus, self
      assembling capsids formed from coded subunits can serve as addressable
      nanocontainers or custom-made structural elements.

PMID- 18093951
TI  - Differential Apaf-1 levels allow cytochrome c to induce apoptosis in brain tumors
      but not in normal neural tissues.
AB  - Brain tumors are typically resistant to conventional chemotherapeutics, most of
      which initiate apoptosis upstream of mitochondrial cytochrome c release. In this
      study, we demonstrate that directly activating apoptosis downstream of the
      mitochondria, with cytosolic cytochrome c, kills brain tumor cells but not normal
      brain tissue. Specifically, cytosolic cytochrome c is sufficient to induce
      apoptosis in glioblastoma and medulloblastoma cell lines. In contrast, primary
      neurons from the cerebellum and cortex are remarkably resistant to cytosolic
      cytochrome c. Importantly, tumor tissue from mouse models of both high-grade
      astrocytoma and medulloblastoma display hypersensitivity to cytochrome c when
      compared with surrounding brain tissue. This differential sensitivity to
      cytochrome c is attributed to high Apaf-1 levels in the tumor tissue compared
      with low Apaf-1 levels in the adjacent brain tissue. These differences in Apaf-1
      abundance correlate with differences in the levels of E2F1, a previously
      identified activator of Apaf-1 transcription. ChIP assays reveal that E2F1 binds
      the Apaf-1 promoter specifically in tumor tissue, suggesting that E2F1
      contributes to the expression of Apaf-1 in brain tumors. Together, these results
      demonstrate an unexpected sensitivity of brain tumors to postmitochondrial
      induction of apoptosis. Moreover, they raise the possibility that this phenomenon
      could be exploited therapeutically to selectively kill brain cancer cells while
      sparing the surrounding brain parenchyma.

PMID- 18093952
TI  - CLC Cl /H+ transporters constrained by covalent cross-linking.
AB  - CLC Cl(-)/H(+) exchangers are homodimers with Cl(-)-binding and H(+)-coupling
      residues contained within each subunit. It is not known whether the transport
      mechanism requires conformational rearrangement between subunits or whether each
      subunit operates as a separate exchanger. We designed various cysteine
      substitution mutants on a cysteine-less background of CLC-ec1, a bacterial CLC
      exchanger of known structure, with the aim of covalently linking the subunits.
      The constructs were cross-linked in air or with exogenous oxidant, and the cross
      linked proteins were reconstituted to assess their function. In addition to
      conventional disulfides, a cysteine-lysine cross-bridge was formed with I(2) as
      an oxidant. The constructs, all of which contained one, two, or four cross
      bridges, were functionally active and kinetically competent with respect to Cl(-)
      turnover rate, Cl(-)/H(+) exchange stoichiometry, and H(+) pumping driven by a
      Cl(-) gradient. These results imply that large quaternary rearrangements, such as
      those known to occur for "common gating" in CLC channels, are not necessary for
      the ion transport cycle and that it is therefore likely that the transport
      mechanism is carried out by the subunits working individually, as with "fast
      gating" of the CLC channels.

PMID- 18093953
TI  - Defects in XRCC4 and KU80 differentially affect the joining of distal
      nonhomologous ends.
AB  - XRCC4-null mice have a more severe phenotype than KU80-null mice. Here, we
      address whether this difference in phenotype is connected to nonhomologous end
      joining (NHEJ). We used intrachromosomal substrates to monitor NHEJ of two distal
      double-strand breaks (DSBs) targeted by I-SceI, in living cells. In xrcc4
      defective XR-1 cells, a residual but significant end-joining process exists,
      which primarily uses microhomologies distal from the DSB. However, NHEJ
      efficiency was strongly reduced in xrcc4-defective XR-1 cells versus complemented
      cells, contrasting with KU-deficient xrs6 cells, which showed levels of end
      joining similar to those of complemented cells. Nevertheless, sequence analysis
      of the repair junctions indicated that the accuracy of end-joining was strongly
      affected in both xrcc4-deficient and KU-deficient cells. More specifically, these
      data showed that the KU80/XRCC4 pathway is conservative and not intrinsically
      error-prone but can accommodate non-fully complementary ends at the cost of
      limited mutagenesis.

PMID- 18093954
TI  - Cold- and exercise-induced peak metabolic rates in tropical birds.
AB  - Compared with temperate birds, tropical birds have low reproductive rates, slow
      development as nestlings, and long lifespans. These "slow" life history traits
      are thought to be associated with reduced energy expenditure, or a slow "pace of
      life." To test predictions from this hypothesis, we measured exercise-induced
      peak metabolic rates (PMR(E)) in 45 species of tropical lowland forest birds and
      compared these data with PMR(E) for three temperate species. We also compared
      cold-induced PMR (PMR(C)) with PMR(E) in the same individuals of 19 tropical
      species. Tropical birds had a 39% lower PMR(E) than did the temperate species. In
      tropical birds, PMR(C) and PMR(E) scaled similarly with body mass (M(b)), but
      PMR(E) was 47% higher than PMR(C). PMR(E) averaged 6.44 x basal metabolic rate
      (BMR) and PMR(C) averaged 4.52 x BMR. The slope of the equation relating PMR(E)
      to M(b) exceeded the slope for the equation for BMR vs. M(b), whereas slopes for
      the equations of PMR(C) and BMR vs. M(b) did not differ. M(b)-adjusted residuals
      of PMR(E) were positively correlated with residual BMR, whereas residual PMR(C)
      and residual BMR were not correlated. PMR(E) and PMR(C) were not correlated after
      we corrected for M(b). Temperate birds maintained their body temperature at an
      8.6 degrees C lower average air temperature than did tropical species. The lower
      PMR(E) values in tropical species suggest that their suite of life history traits
      on the slow end of the life history continuum are associated with reduced
      metabolic rates.

PMID- 18093955
TI  - Dynamical magnetostructural properties of Anabaena ferredoxin.
AB  - A mixed quantum/classical investigation of the dynamical magnetostructural
      properties, that is, "magnetodynamics," of oxidized Anabaena PCC7119 ferredoxin
      is carried out at room temperature in two distinct conformational states. This
      protein hosts a [2Fe-2S] cluster in which two iron centers are
      antiferromagnetically coupled to an overall low-spin electronic ground state that
      has a genuine multireference character. To study the magnetodynamics of this
      prosthetic group, an approximate spin projection method is formulated in the
      framework of density functional theory that allows for multideterminant ab initio
      molecular dynamics simulations to be carried out efficiently. By using this
      scheme, the influence of both thermal fluctuations and conformational motion on
      the structure of the [2Fe-2S] cluster and on the dynamics of the
      antiferromagnetic coupling constant, J(t), has been investigated. In addition to
      demonstrating how sensitively the shape of the [2Fe-2S] core itself is affected
      by hydrogen bonding, the analyses reveal a complex dynamical coupling of J to
      both local vibrations and large-amplitude motion. It is shown that this interplay
      can be understood in terms of specific vibrational modes and distinct hydrogen
      bonding patterns between the iron-sulfur cluster and the protein backbone,
      respectively. This implies going beyond the Goodenough-Kanamori rules for angular
      magnetostructural correlations of oxidized iron-sulfur prosthetic groups.

PMID- 18093956
TI  - Molecular dynamics simulations suggest a mechanism for translocation of the HIV-1
      TAT peptide across lipid membranes.
AB  - The recombinant HIV-1 Tat protein contains a small region corresponding to
      residues (47)YGRKKRRQRR(57)R, which is capable of translocating cargoes of
      different molecular sizes, such as proteins, DNA, RNA, or drugs, across the cell
      membrane in an apparently energy-independent manner. The pathway that these
      peptides follow for entry into the cell has been the subject of strong
      controversy for the last decade. This peptide is highly basic and hydrophilic.
      Therefore, a central question that any candidate mechanism has to answer is how
      this highly hydrophilic peptide is able to cross the hydrophobic barrier imposed
      by the cell membrane. We propose a mechanism for the spontaneous translocation of
      the Tat peptides across a lipid membrane. This mechanism involves strong
      interactions between the Tat peptides and the phosphate groups on both sides of
      the lipid bilayer, the insertion of charged side chains that nucleate the
      formation of a transient pore, followed by the translocation of the Tat peptides
      by diffusing on the pore surface. This mechanism explains how key ingredients,
      such as the cooperativity among the peptides, the large positive charge, and
      specifically the arginine amino acids, contribute to the uptake. The proposed
      mechanism also illustrates the importance of membrane fluctuations. Indeed,
      mechanisms that involve large fluctuations of the membrane structure, such as
      transient pores and the insertion of charged amino acid side chains, may be
      common and perhaps central to the functions of many membrane protein functions.

PMID- 18093958
TI  - Profile of Mark E. Davis.

PMID- 18093957
TI  - Thiamine biosynthesis in algae is regulated by riboswitches.
AB  - In bacteria, many genes involved in the biosynthesis of cofactors such as
      thiamine pyrophosphate (TPP) are regulated by ribo switches, regions in the 5'
      end of mRNAs to which the cofactor binds, thereby affecting translation and/or
      transcription. TPP riboswitches have now been identified in fungi, in which they
      alter mRNA splicing. Here, we show that addition of thiamine to cultures of the
      model green alga Chlamydomonas reinhardtii alters splicing of transcripts for the
      THI4 and THIC genes, encoding the first enzymes of the thiazole and pyrimidine
      branches of thiamine biosynthesis, respectively, concomitant with an increase in
      intracellular thiamine and TPP levels. Comparison with Volvox carteri, a related
      alga, revealed highly conserved regions within introns of these genes. Inspection
      of the sequences identified TPP riboswitch motifs, and RNA transcribed from the
      regions binds TPP in vitro. The THI4 riboswitch, but not the promoter region, was
      found to be necessary and sufficient for thiamine to repress expression of a
      luciferase-encoding reporter construct in vivo. The pyr1 mutant of C.
      reinhardtii, which is resistant to the thiamine analogue pyrithiamine, has a
      mutation in the THI4 riboswitch that prevents the THI4 gene from being repressed
      by TPP. By the use of these ribo switches, thiamine biosynthesis in C.
      reinhardtii can be effectively regulated at physiological concentrations of the
      vitamin.

PMID- 18093959
TI  - The drifting human genome.

PMID- 18093960
TI  - Li-decorated metal-organic framework 5: a route to achieving a suitable hydrogen
      storage medium.
AB  - A significant improvement in molecular hydrogen uptake properties is revealed by
      our ab initio calculations for Li-decorated metal-organic framework 5. We have
      found that two Li atoms are strongly adsorbed on the surfaces of the six-carbon
      rings, one on each side, carrying a charge of +0.9e per Li atom. Each Li can
      cluster three H(2) molecules around itself with a binding energy of 12 kJ (mol
      H(2))(-1). Furthermore, we show from ab initio molecular dynamics simulations
      with a hydrogen loading of 18 H(2) per formula unit that a hydrogen uptake of 2.9
      wt % at 200 K and 2.0 wt % at 300 K is achievable. To our knowledge, this is the
      highest hydrogen storage capacity reported for metal-organic framework 5 under
      such thermodynamic conditions.

PMID- 18093961
TI  - BMP signaling mediates stem/progenitor cell-induced retina regeneration.
AB  - We identified a mechanism whereby retina regeneration in the embryonic chick can
      be induced by the contribution of stem/progenitor cells. We show that bone
      morphogenetic protein (BMP) signaling is sufficient and necessary to induce
      retina regeneration and that its action can be divided into two phases. By 3 days
      after postretinectomy (d PR), the BMP pathway directs proliferation and
      regeneration through the activation of Smad (canonical BMP pathway) and the up
      regulation of FGF signaling by the MAPK pathway. By 7d PR, it induces apoptosis
      by activating p38 (a noncanonical BMP pathway) and down-regulating FGF signaling
      (by both MAPK and AKT pathways). Apoptosis at this later stage can be prevented,
      and BMP-induced regeneration can be further induced by inhibition of p38. These
      results unravel a mechanism for stem/progenitor cell-mediated retina
      regeneration, where BMP activation establishes a cross-talk with the FGF pathway
      and selectively activates the canonical and noncanonical BMP pathways. Retina
      stem/progenitor cells exist in other species, including humans. Thus, our
      findings provide insights on how retinal stem cells can be activated for possible
      regenerative therapies.

PMID- 18093963
TI  - Is prognosis in the individual, the environment, the disease, or what?

PMID- 18093962
TI  - Use of depot antipsychotic medications for medication nonadherence in
      schizophrenia.
AB  - OBJECTIVES: To describe factors associated with initiation of depot antipsychotic
      medications in psychiatric outpatients with schizophrenia and recent medication
      nonadherence. METHODS: A national sample of psychiatrists reported on adult
      outpatients with schizophrenia who were nonadherent with oral antipsychotic
      medications in the last year. RESULTS: In total, 17.6% of psychiatrists initiated
      depot antipsychotic injections. Initiation was significantly and positively
      associated with public insurance, prior inpatient admission, proportion of time
      nonadherent, average or above average intellectual functioning, and living in a
      mental health residence. Use was inversely associated with using second
      generation antipsychotics and other oral psychotropic medications prior to
      medication nonadherence. Psychiatrists who were male, nonwhite, and more
      optimistic about managing nonadherence were more likely to initiate depot
      injections. CONCLUSIONS: Initiation of depot injections is a joint function of
      patient, physician, treatment, and setting factors. Use of long-acting
      preparations in this population is uncommon despite clinical recommendations
      urging their use.

PMID- 18093964
TI  - Amino acids and nitrate as signals for the regulation of nitrogen acquisition.
AB  - The uptake of nitrogen (N) by roots is known to change with supply in a manner
      that suggests that the N status of plants is somehow sensed and can feedback to
      regulate this process. The most abundant source of N in soils for crops is
      nitrate. Uptake systems for nitrate, ammonium, and amino acids are present in the
      roots of most plants including crops. As nitrate is assimilated via conversion to
      nitrite, then ammonium into amino acids, it has been suggested that the internal
      pools of amino acids within plants may indicate nitrogen status by providing a
      signal that can regulate nitrate uptake by the plant. In support of this idea,
      both nitrate and ammonium influx and transporter transcript were shown to
      decrease in root tissue treated with exogenously applied amino acids. Several
      different amino acids have been tested for their effects on influx and
      transcription and glutamine was most effective. The feedback regulation occurs by
      changing the expression of transporters, but may also involve the post
      translational modification of proteins. For example, some of the cytoplasmic
      enzymes responsible for nitrate assimilation are regulated by phosphorylation and
      binding of a 14-3-3 protein. The effects of treating plants with glutamine have
      been examined, first to identify the uptake of the amino acid and then to measure
      tissue nitrate reductase activity and cellular pools of nitrate. These results
      are reviewed in terms of feedback regulation and the putative cell sensing
      systems for N status including a possible specific role for cytosolic nitrate.

PMID- 18093965
TI  - Complementary hierarchical clustering.
AB  - When applying hierarchical clustering algorithms to cluster patient samples from
      microarray data, the clustering patterns generated by most algorithms tend to be
      dominated by groups of highly differentially expressed genes that have closely
      related expression patterns. Sometimes, these genes may not be relevant to the
      biological process under study or their functions may already be known. The
      problem is that these genes can potentially drown out the effects of other genes
      that are relevant or have novel functions. We propose a procedure called
      complementary hierarchical clustering that is designed to uncover the structures
      arising from these novel genes that are not as highly expressed. Simulation
      studies show that the procedure is effective when applied to a variety of
      examples. We also define a concept called relative gene importance that can be
      used to identify the influential genes in a given clustering. Finally, we analyze
      a microarray data set from 295 breast cancer patients, using clustering with the
      correlation-based distance measure. The complementary clustering reveals a
      grouping of the patients which is uncorrelated with a number of known prognostic
      signatures and significantly differing distant metastasis-free probabilities.

PMID- 18093966
TI  - Return-to-work policies in Finnish occupational health services.
AB  - AIM: To describe return-to-work services for employees on sick leave offered by
      Finnish occupational health services (OHS). METHODS: Finnish OHS are surveyed
      every 3 years. Respondents are asked if they offer services to facilitate return
      to work (RTW), and if so, to describe them. The description was qualitatively
      analysed using the Atlas-ti programme to find the themes that best describe the
      services. We also studied characteristics of OHS predicting a return-to-work
      policy. RESULTS: Of the total sample of 969 occupational health units, 95%
      responded to the survey. Forty-one per cent reported offering services for
      facilitating RTW after sick leave. The service usually consisted of occupational
      physician examination of employees on sick leave for approximately 6 weeks. This
      was followed by a joint discussion between employee, physician and supervisor,
      which could result in work accommodation or a work trial period. There was a
      substantial variation, with only 10% mentioning a joint meeting and 13%
      mentioning a work trial period or work accommodation. Return-to-work policies
      were more frequently found in the OHS that served only a few employers, provided
      more group activities and collaborated more with employers and research
      institutes. CONCLUSION: Less than half of Finnish OHS offer return-to-work
      services of which the contents show wide variation that is not in line with
      current scientific evidence. A guideline project for return-to-work practices is
      needed to fill the gap. More research is needed to best define monitoring and
      screening practices for workers on sick leave.

PMID- 18093967
TI  - Learning how to be a scientist.

PMID- 18093968
TI  - Structure and catalytic mechanism of eukaryotic selenocysteine synthase.
AB  - In eukaryotes and Archaea, selenocysteine synthase (SecS) converts O-phospho-L
      seryl-tRNA [Ser]Sec into selenocysteyl-tRNA [Ser]Sec using selenophosphate as the
      selenium donor compound. The molecular mechanisms underlying SecS activity are
      presently unknown. We have delineated a 450-residue core of mouse SecS, which
      retained full selenocysteyl-tRNA [Ser]Sec synthesis activity, and determined its
      crystal structure at 1.65 A resolution. SecS exhibits three domains that place it
      in the fold type I family of pyridoxal phosphate (PLP)-dependent enzymes. Two
      SecS monomers interact intimately and together build up two identical active
      sites around PLP in a Schiff-base linkage with lysine 284. Two SecS dimers
      further associate to form a homotetramer. The N terminus, which mediates tetramer
      formation, and a large insertion that remodels the active site set SecS aside
      from other members of the family. The active site insertion contributes to PLP
      binding and positions a glutamate next to the PLP, where it could repel
      substrates with a free alpha-carboxyl group, suggesting why SecS does not act on
      free O-phospho-l-serine. Upon soaking crystals in phosphate buffer, a previously
      disordered loop within the active site insertion contracted to form a phosphate
      binding site. Residues that are strictly conserved in SecS orthologs but variant
      in related enzymes coordinate the phosphate and upon mutation corrupt SecS
      activity. Modeling suggested that the phosphate loop accommodates the gamma
      phosphate moiety of O-phospho-l-seryl-tRNA [Ser]Sec and, after phosphate
      elimination, binds selenophosphate to initiate attack on the proposed
      aminoacrylyl-tRNA [Ser]Sec intermediate. Based on these results and on the
      activity profiles of mechanism-based inhibitors, we offer a detailed reaction
      mechanism for the enzyme.

PMID- 18093969
TI  - Crystal structure of the major periplasmic domain of the bacterial membrane
      protein assembly facilitator YidC.
AB  - The essential bacterial membrane protein YidC facilitates insertion and assembly
      of proteins destined for integration into the inner membrane. It has homologues
      in both mitochondria and chloroplasts. Here we report the crystal structure of
      the Escherichia coli YidC major periplasmic domain (YidCECP1) at 2.5A resolution.
      This domain is present in YidC from Gram-negative bacteria and is more than half
      the size of the full-length protein. The structure reveals that YidCECP1 is made
      up of a large twisted beta-sandwich protein fold with a C-terminal alpha-helix
      that packs against one face of the beta-sandwich. Our structure and sequence
      analysis reveals that the C-terminal alpha-helix and the beta-sheet that it lays
      against are the most conserved regions of the domain. The region corresponding to
      the C-terminal alpha-helix was previously shown to be important for the protein
      insertase function of YidC and is conserved in other YidC-like proteins. The
      structure reveals that a region of YidC that was previously shown to be involved
      in binding to SecF maps to one edge of the beta-sandwich. Electrostatic analysis
      of the molecular surface for this region of YidC reveals a predominantly charged
      surface and suggests that the SecF-YidC interaction may be electrostatic in
      nature. Interestingly, YidCECP1 has significant structural similarity to
      galactose mutarotase from Lactococcus lactis, suggesting that this domain may
      have another function besides its role in membrane protein assembly.

PMID- 18093970
TI  - Retinyl ester formation by lecithin: retinol acyltransferase is a key regulator
      of retinoid homeostasis in mouse embryogenesis.
AB  - The developing mammalian embryo is entirely dependent on the maternal circulation
      for its supply of retinoids (vitamin A and its metabolites). The mechanisms
      through which mammalian developing tissues maintain adequate retinoid levels in
      the face of suboptimal or excessive maternal dietary vitamin A intake have not
      been established. We investigated the role of retinyl ester formation catalyzed
      by lecithin:retinol acyltransferase (LRAT) in regulating retinoid homeostasis
      during embryogenesis. Dams lacking both LRAT and retinol-binding protein (RBP),
      the sole specific carrier for retinol in serum, were maintained on diets
      containing different amounts of vitamin A during pregnancy. We hypothesized that
      the lack of both proteins would make the embryo more vulnerable to changes in
      maternal dietary vitamin A intake. Our data demonstrate that maternal dietary
      vitamin A deprivation during pregnancy generates a severe retinoid-deficient
      phenotype of the embryo due to the severe retinoid-deficient status of the double
      mutant dams rather than to the lack of LRAT in the developing tissues. Moreover,
      in the case of excessive maternal dietary vitamin A intake, LRAT acts together
      with Cyp26A1, one of the enzymes that catalyze the degradation of retinoic acid,
      and possibly with STRA6, the recently identified cell surface receptor for
      retinol-RBP, in maintaining adequate levels of retinoids in embryonic and
      extraembryonic tissues. In contrast, the pathway of retinoic acid synthesis does
      not contribute significantly to regulating retinoid homeostasis during mammalian
      development except under conditions of severe maternal retinoid deficiency.

PMID- 18093971
TI  - Molecular perspective of antigen-mediated mast cell signaling.
AB  - Antigen-mediated cross-linking of the high affinity receptor for IgE (Fc epsilon
      RI), in the plasma membrane of mast cells, is the first step in the allergic
      immune response. This event triggers the phosphorylation of specific tyrosines in
      the cytoplasmic segments of the beta and gamma subunits of Fc epsilon RI by the
      Src tyrosine kinase Lyn, which is anchored to the inner leaflet of the plasma
      membrane. Lyn-induced phosphorylation of Fc epsilon RI occurs in a cholesterol
      dependent manner, leading to the hypothesis that cholesterol-rich domains, or
      "lipid rafts," may act as functional platforms for IgE receptor signaling.
      Testing this hypothesis under physiological conditions remains challenging
      because of the notion that these functional domains are likely transient and much
      smaller than the diffraction limit of optical microscopy. Here we use ultrafast
      fluorescence dynamics to investigate the correlation between nanostructural
      changes in the plasma membrane (labeled with 1,1'-dioctadecyl-3,3,3',3'
      tetramethyl-indocarbocyanine (diI-C18)) and IgE-Fc epsilon RI cross-linking in
      adherent RBL mast cells stimulated with multivalent antigen. Time-dependent two
      photon fluorescence lifetime imaging microscopy of diI-C18 shows changes in
      lifetime that agree with the kinetics of stimulated tyrosine phosphorylation of
      Fc epsilon RI, the first identifiable biochemical step of the allergic response,
      under the same conditions. In addition, two-photon fluorescence lifetime imaging
      microscopy of Alexa Fluor 488-labeled IgE indicates that Forster resonance energy
      transfer occurs with diI-C18 in the plasma membrane. Our live cell studies
      provide direct evidence for the association of IgE-Fc epsilon RI with specialized
      cholesterol-rich domains within approximately 4-nm proximity and with an energy
      transfer efficiency of 0.22 +/- 0.01 at maximal association during IgE receptor
      signaling.

PMID- 18093972
TI  - Ubiquitination and degradation of homeodomain-interacting protein kinase 2 by
      WD40 repeat/SOCS box protein WSB-1.
AB  - Homeodomain-interacting protein kinase 2 (HIPK2) is a member of the nuclear
      protein kinase family, which induces both p53- and CtBP-mediated apoptosis.
      Levels of HIPK2 were increased by UV irradiation and cisplatin treatment, thereby
      implying the degradation of HIPK2 in cells under normal conditions. Here, we
      indicate that HIPK2 is ubiquitinated and degraded by the WD40-repeat/SOCS box
      protein WSB-1, a process that is blocked under DNA damage conditions. Yeast two
      hybrid screening was conducted to identify the proteins that interact with HIPK2.
      WSB-1, an E3 ubiquitin ligase, was characterized as an HIPK2-interacting protein.
      The coexpression of WSB-1 resulted in the degradation of HIPK2 via its C-terminal
      region. Domain analysis of WSB-1 showed that WD40-repeats and the SOCS box were
      required for its interaction with and degradation of HIPK2, respectively. In
      support of the degradation of HIPK2 by WSB-1, HIPK2 was polyubiquitinated by WSB
      1 in vitro and in vivo. The knockdown of endogenous WSB-1 with the expression of
      short hairpin RNA against WSB-1 increases the stability of endogenous HIPK2 and
      resulted in the accumulation of HIPK2. The ubiquitination and degradation of
      HIPK2 by WSB-1 was inhibited completely via the administration of DNA damage
      reagents, including Adriamycin and cisplatin. These findings effectively
      illustrate the regulatory mechanisms by which HIPK2 is maintained at a low level,
      by WSB-1 in cells under normal conditions, and stabilized by genotoxic stresses.

PMID- 18093973
TI  - Protein-tyrosine phosphatase epsilon regulates Shc signaling in a kinase-specific
      manner: increasing coherence in tyrosine phosphatase signaling.
AB  - Individual protein tyrosine kinases and phosphatases target multiple substrates;
      this may generate conflicting signals, possibly within a single pathway. Protein
      tyrosine phosphatase epsilon (PTPepsilon) performs two potentially opposing
      roles: in Neu-induced mammary tumors, PTPepsilon activates Src downstream of Neu,
      whereas in other systems PTPepsilon can indirectly down-regulate MAP kinase
      signaling. We now show that the latter effect is mediated at least in part via
      the adaptor protein Shc. PTPepsilon binds and dephosphorylates Shc in vivo,
      reducing the association of Shc with Grb2 and inhibiting downstream ERK
      activation. PTPepsilon binds Shc in a phosphotyrosine-independent manner mediated
      by the Shc PTB domain and aided by a sequence of 10 N-terminal residues in
      PTPepsilon. Surprisingly, PTPepsilon dephosphorylates Shc in a kinase-dependent
      manner; PTPepsilon targets Shc in the presence of Src but not in the presence of
      Neu. Using a series of point mutants of Shc and Neu, we show that Neu protects
      Shc from dephosphorylation by binding the PTB domain of Shc, most likely
      competing against PTPepsilon for binding the same domain. In agreement,
      PTPepsilon dephosphorylates Shc in mouse embryo fibroblasts but not in Neu
      induced mammary tumor cells. We conclude that in the context of Neu-induced
      mammary tumor cells, Neu prevents PTPepsilon from targeting Shc and from reducing
      its promitogenic signal while phosphorylating PTPepsilon and directing it to
      activate Src in support of mitogenesis. In so doing, Neu contributes to the
      coherence of the promitogenic role of PTPepsilon in this system.

PMID- 18093974
TI  - Mediator requirement downstream of chromatin remodeling during transcriptional
      activation of CHA1 in yeast.
AB  - Mediator complex is essential for transcription by RNA polymerase II in
      eukaryotes. Although chromatin remodeling is an integral part of transcriptional
      activation at many promoters, whether Mediator is required for this function has
      not been determined. Here we have used the yeast CHA1 gene to study the role of
      Mediator in chromatin remodeling and recruitment of the transcription machinery.
      We show by chromatin immunoprecipitation that Mediator subunits are recruited to
      the induced CHA1 promoter. Inactivation of Mediator at 37 degrees C in yeast
      harboring the srb4-138 (med17) ts mutation severely reduces CHA1 activation and
      prevents recruitment to the induced CHA1 promoter of Med18/Srb5, from the head
      module of Mediator, and Med14/Rgr1, which bridges the middle and tail modules. In
      contrast, recruitment of Med15/Gal11 from the tail module is unaffected in med17
      ts yeast at 37 degrees C. Recruitment of TATA-binding protein (TBP) is severely
      compromised in the absence of functional Mediator, whereas Kin28 and polymerase
      II recruitment are reduced but to a lesser extent. Induced levels of histone
      H3K4me3 at the CHA1 promoter are not diminished by inactivation of Mediator,
      whereas recruitment of Paf1 and of Ser2- and Ser5-phosphorylated forms of Rbp1
      are reduced but not eliminated. Loss of histone H3 from the induced CHA1 promoter
      is seen in wild type yeast but is greatly reduced by loss of intact Mediator. In
      contrast, Swi/Snf recruitment and nucleosome remodeling are unaffected by loss of
      Mediator function. Thus, Mediator is required for recruitment of the
      transcription machinery subsequent to chromatin remodeling during CHA1 induction.

PMID- 18093975
TI  - Isx participates in the maintenance of vitamin A metabolism by regulation of beta
      carotene 15,15'-monooxygenase (Bcmo1) expression.
AB  - Isx (intestine specific homeobox) is an intestine-specific transcription factor.
      To elucidate its physiological function, we generated Isx-deficient mice by
      knocking in the beta-galactosidase gene (LacZ) in the Isx locus (IsxLacZ/LacZ
      mice). LacZ staining of heterozygous (IsxLacZ/+) mice revealed that Isx was
      expressed abundantly in intestinal epithelial cells from duodenum to proximal
      colon. Quantitative mRNA expression profiling of duodenum and jejunum showed that
      beta-carotene 15,15'-monooxygenase (EC1.14.99.36 Bcmo1) and the class B type I
      scavenger receptor, which are involved in vitamin A synthesis and carotenoid
      uptake, respectively, were drastically increased in IsxLacZ/LacZ mice. Although
      mild vitamin A deficiency decreased Isx expression in duodenum of wild-type
      (Isx+/+) mice, severe vitamin A deficiency decreased Isx mRNA expression in both
      duodenum and jejunum of Isx+/+ mice. On the other hand, vitamin A deficiency
      increased Bcmo1 expression in both duodenum and jejunum of Isx+/+ mice. However,
      Bcmo1 expression was not increased in duodenum of IsxLacZ/LacZ mice by mild
      vitamin A deficiency. These data suggest that Isx participates in the maintenance
      of vitamin A metabolism by regulating Bcmo1 expression in the intestine.

PMID- 18093976
TI  - In vitro and in cellulo evidences for association of the survival of motor neuron
      complex with the fragile X mental retardation protein.
AB  - Spinal muscular atrophy (SMA) is caused by reduced levels of the survival of
      motor neuron (SMN) protein. Although the SMN complex is essential for assembly of
      spliceosomal U small nuclear RNPs, it is still not understood why reduced levels
      of the SMN protein specifically cause motor neuron degeneration. SMN was recently
      proposed to have specific functions in mRNA transport and translation regulation
      in neuronal processes. The defective protein in Fragile X mental retardation
      syndrome (FMRP) also plays a role in transport of mRNPs and in their translation.
      Therefore, we examined possible relationships of SMN with FMRP. We observed
      granules containing both transiently expressed red fluorescent protein(RFP)
      tagged SMN and green fluorescent protein(GFP)-tagged FMRP in cell bodies and
      processes of rat primary neurons of hypothalamus in culture. By
      immunoprecipitation experiments, we detected an association of FMRP with the SMN
      complex in human neuroblastoma SH-SY5Y cells and in murine motor neuron MN-1
      cells. Then, by in vitro experiments, we demonstrated that the SMN protein is
      essential for this association. We showed that the COOH-terminal region of FMRP,
      as well as the conserved YG box and the region encoded by exon 7 of SMN, are
      required for the interaction. Our findings suggest a link between the SMN complex
      and FMRP in neuronal cells.

PMID- 18093977
TI  - Nucleotide-induced structural changes in P-glycoprotein observed by electron
      microscopy.
AB  - P-glycoprotein (Pgp) is an ATP hydrolysis driven multidrug efflux pump, which,
      when overexpressed in the plasma membrane of certain cancers, can lead to the
      failure of chemotherapy. Previously, we have presented a projection structure of
      nucleotide-free mouse Pgp from electron microscopic images of lipid monolayer
      generated two-dimensional crystals ( Lee, J. Y., Urbatsch, I. L., Senior, A. E.,
      and Wilkens, S. (2002) J. Biol. Chem. 277, 40125-40131 ). Here we have analyzed
      the structure of cysteine-free human Pgp from two-dimensional crystals that were
      generated with the same lipid-monolayer technique in the absence and presence of
      various nucleotides. The images show that human Pgp has a similar structure to
      the mouse protein. Furthermore, the analysis of projection structures obtained
      under different nucleotide conditions suggests that Pgp can exist in at least two
      major conformations, one of which shows a central cavity between the N- and C
      terminal halves of the molecule and another in which the two halves have moved
      sideways, thereby closing the central cavity. Intermediate conformations were
      observed for some nucleotide/vanadate combinations. A low-resolution, three
      dimensional model of human Pgp was calculated from tilted specimen crystallized
      in the presence of the non-hydrolyzable nucleotide analog, adenosine 5'-O
      (thiotriphosphate). The structural analysis presented here adds to the emerging
      picture that multidrug ABC transporters function by switching between two major
      conformations in a nucleotide-dependent manner.

PMID- 18093978
TI  - Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells
      negatively regulates c-Myb-mediated transactivation through small ubiquitin
      related modifier-1 modification.
AB  - Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an adaptor/scaffold
      protein that mediates several important signaling pathways, including the tumor
      necrosis factor-R:NF-kappaB pathway, involved in immune surveillance,
      inflammation, etc. Because most studies of TRAF6 function have focused primarily
      on its role as an adaptor molecule in signaling pathways in the cytoplasm, the
      potential functions of TRAF6 in other cellular compartments has not been
      previously investigated. Here, we demonstrate that TRAF6 resides not only in the
      cellular cytoplasm but is also found in the nuclei of both normal and malignant B
      lymphocytes. TRAF6 does not possess a nuclear localization signal but enters the
      nucleus through the nuclear pore complex containing RanGap1. Chromatin
      immunoprecipitation cloning experiments demonstrated that nuclear TRAF6
      associates with c-Myb within the 5'-end of the c-Myb promoter. Further analysis
      showed that nuclear TRAF6 is modified by small ubiquitin-related modifier-1,
      interacts with histone deacetylase 1, and represses c-Myb-mediated
      transactivation. Thus, TRAF6 negatively regulates c-Myb through a novel repressor
      function in the nuclei of both normal and malignant B-lymphocytes that could
      represent a novel control mechanism that maintains cell homeostasis and immune
      surveillance.

PMID- 18093979
TI  - Identification of novel toxicity-associated metabolites by metabolomics and mass
      isotopomer analysis of acetaminophen metabolism in wild-type and Cyp2e1-null
      mice.
AB  - CYP2E1 is recognized as the most important enzyme for initiation of acetaminophen
      (APAP)-induced toxicity. In this study, the resistance of Cyp2e1-null mice to
      APAP treatment was confirmed by comparing serum aminotransferase activities and
      blood urea nitrogen levels in wild-type and Cyp2e1-null mice. However,
      unexpectedly, profiling of major known APAP metabolites in urine and serum
      revealed that the contribution of CYP2E1 to APAP metabolism decreased with
      increasing APAP doses administered. Measurement of hepatic glutathione and
      hydrogen peroxide levels exposed the importance of oxidative stress in
      determining the consequence of APAP overdose. Subsequent metabolomic analysis was
      capable of constructing a principal components analysis (PCA) model that
      delineated a relationship between urinary metabolomes and the responses to APAP
      treatment. Urinary ions high in wild-type mice treated with 400 mg/kg APAP were
      elucidated as 3-methoxy-APAP glucuronide (VII) and three novel APAP metabolites,
      including S-(5-acetylamino-2-hydroxyphenyl)mercaptopyruvic acid (VI, formed by a
      Cys-APAP transamination reaction in kidney), 3,3'-biacetaminophen (VIII, an APAP
      dimer), and a benzothiazine compound (IX, originated from deacetylated APAP),
      through mass isotopomer analysis, accurate mass measurement, tandem mass
      spectrometry fragmentation, in vitro reactions, and chemical treatments. Dose-,
      time-, and genotype-dependent appearance of these minor APAP metabolites implied
      their association with the APAP-induced toxicity and potential biomarker
      application. Overall, the oxidative stress elicited by CYP2E1-mediated APAP
      metabolism might significantly contribute to APAP-induced toxicity. The
      combination of genetically modified animal models, mass isotopomer analysis, and
      metabolomics provides a powerful and efficient technical platform to characterize
      APAP-induced toxicity through identifying novel biomarkers and unraveling novel
      mechanisms.

PMID- 18093980
TI  - Subunit-specific protein footprinting reveals significant structural
      rearrangements and a role for N-terminal Lys-14 of HIV-1 Integrase during viral
      DNA binding.
AB  - To identify functional contacts between HIV-1 integrase (IN) and its viral DNA
      substrate, we devised a new experimental strategy combining the following two
      methodologies. First, disulfide-mediated cross-linking was used to site
      specifically link select core and C-terminal domain amino acids to respective
      positions in viral DNA. Next, surface topologies of free IN and IN-DNA complexes
      were compared using Lys- and Arg-selective small chemical modifiers and mass
      spectrometric analysis. This approach enabled us to dissect specific contacts
      made by different monomers within the multimeric complex. The foot-printing
      studies for the first time revealed the importance of a specific N-terminal
      domain residue, Lys-14, in viral DNA binding. In addition, a DNA-induced
      conformational change involving the connection between the core and C-terminal
      domains was observed. Site-directed mutagenesis experiments confirmed the
      importance of the identified contacts for recombinant IN activities and virus
      infection. These new findings provided major constraints, enabling us to identify
      the viral DNA binding channel in the active full-length IN multimer. The
      experimental approach described here has general application to mapping
      interactions within functional nucleoprotein complexes.

PMID- 18093981
TI  - A sensitive flow cytometry-based nucleotide excision repair assay unexpectedly
      reveals that mitogen-activated protein kinase signaling does not regulate the
      removal of UV-induced DNA damage in human cells.
AB  - In response to diverse genotoxic stimuli (e.g. UV and cisplatin), the mitogen
      activated protein kinases ERK1/2, JNK1/2, and p38alpha/beta become rapidly
      phosphorylated and in turn activate multiple downstream effectors that modulate
      apoptosis and/or growth arrest. Furthermore, previous lines of evidence have
      strongly suggested that ERK1/2 and JNK1/2 participate in global-genomic
      nucleotide excision repair, a critical antineoplastic pathway that removes helix
      distorting DNA adducts induced by a variety of mutagenic agents, including UV. To
      rigorously evaluate the potential role of mitogen-activated protein kinases in
      global-genomic nucleotide excision repair, various human cell strains (primary
      skin fibroblasts, primary lung fibroblasts, and HCT116 colon carcinoma cells)
      were treated with highly specific chemical inhibitors, which, following UV
      exposure, (i) abrogated the capacities of ERK1/2, JNK1/2, or p38alpha/beta to
      phosphorylate specific downstream effectors and (ii) characteristically modulated
      cellular proliferation, clonogenic survival, and/or apoptosis. A highly sensitive
      flow cytometry-based nucleotide excision repair assay recently optimized and
      validated in our laboratory was then employed to directly demonstrate that the
      kinetics of UV DNA photoadduct repair are highly similar in mock-treated versus
      mitogen-activated protein kinase inhibitor-treated cells. These data on primary
      and tumor cells treated with pharmacological inhibitors were fully corroborated
      by repair studies using (i) short hairpin RNA-mediated knockdown of ERK1/2 or
      JNK1/2 in human U2OS osteosarcoma cells and (ii) expression of a dominant
      negative p38alpha mutant in human primary lung fibroblasts. Our results provide
      solid evidence for the first time, in disaccord with a burgeoning perception,
      that mitogen-activated protein kinase signaling does not influence the efficiency
      of human global-genomic nucleotide excision repair.

PMID- 18093982
TI  - A structural-dynamical characterization of human Cox17.
AB  - Human Cox17 is a key mitochondrial copper chaperone responsible for supplying
      copper ions, through the assistance of Sco1, Sco2, and Cox11, to cytochrome c
      oxidase, the terminal enzyme of the mitochondrial energy transducing respiratory
      chain. A structural and dynamical characterization of human Cox17 in its various
      functional metallated and redox states is presented here. The NMR solution
      structure of the partially oxidized Cox17 (Cox17(2S-S)) consists of a coiled coil
      helix-coiled coil-helix domain stabilized by two disulfide bonds involving
      Cys(25)-Cys(54) and Cys(35)-Cys(44), preceded by a flexible and completely
      unstructured N-terminal tail. In human Cu(I)Cox17(2S-S) the copper(I) ion is
      coordinated by the sulfurs of Cys(22) and Cys(23), and this is the first example
      of a Cys-Cys binding motif in copper proteins. Copper(I) binding as well as the
      formation of a third disulfide involving Cys(22) and Cys(23) cause structural and
      dynamical changes only restricted to the metal-binding region. Redox properties
      of the disulfides of human Cox17, here investigated, strongly support the current
      hypothesis that the unstructured fully reduced Cox17 protein is present in the
      cytoplasm and enters the intermembrane space (IMS) where is then oxidized by
      Mia40 to Cox17(2S-S), thus becoming partially structured and trapped into the
      IMS. Cox17(2S-S) is the functional species in the IMS, it can bind only one
      copper(I) ion and is then ready to enter the pathway of copper delivery to
      cytochrome c oxidase. The copper(I) form of Cox17(2S-S) has features specific for
      copper chaperones.

PMID- 18093983
TI  - The surfactant peptide KL4 in lipid monolayers: phase behavior, topography, and
      chemical distribution.
AB  - Studies of different fragments and mutants of SP-B suggest that the function
      related structural and compositional characteristics in SP-B are its positive
      charges with intermittent hydrophobic domains. KL4 ([lysine-(leucine)4]4-lysine)
      is a synthetic peptide based on SP-B structure and is the major constituent of
      Surfaxin, a potential therapeutic agent for respiratory distress syndrome in
      premature infants. There is, however, no clear understanding about the possible
      lipid-KL4 interactions behind its function, which is an inevitable knowledge to
      design improved therapeutic agents. To examine the phase behavior, topography,
      and lipid specificity of KL4/lipid systems, we aimed to study different
      surfactant model systems containing KL4, neutral dipalmitoylphosphatidylcholine
      (DPPC) and/or negatively charged dipalmitoylphosphatidylglycerol (DPPG) in the
      presence of Ca2+ ions. Surface pressure-area isotherms, fluorescence microscopic
      images, scanning force microscopy as well as time-of-flight secondary ion mass
      spectrometry suggest (i) that KL4 is not miscible with DPPC and therefore forms
      peptide aggregates in DPPC/KL4 mixtures; (ii) that KL4 specifically interacts
      with DPPG via electrostatic interactions and induces percolation of DPPG-rich
      phases; (iii) that existing DPPG-Ca2+ interactions are too strong to be overcome
      by KL4, the reason why the peptide remains excluded from condensed DPPG domains
      and passively colocalizes with DPPC in a demixed fluid phase; and (iv) that the
      presence of negatively charged lipid is necessary for the formation of bilayer
      protrusions. These results indicate that the capability of the peptide to induce
      the formation of a defined surface-confined reservoir depends on the lipid
      environment, especially on the presence of anionic lipids.

PMID- 18093984
TI  - Structural basis for catalytic and inhibitory mechanisms of beta-hydroxyacyl-acyl
      carrier protein dehydratase (FabZ).
AB  - beta-Hydroxyacyl-acyl carrier protein dehydratase (FabZ) is an important enzyme
      for the elongation cycles of both saturated and unsaturated fatty acids
      biosyntheses in the type II fatty acid biosynthesis system (FAS II) pathway. FabZ
      has been an essential target for the discovery of compounds effective against
      pathogenic microbes. In this work, to characterize the catalytic and inhibitory
      mechanisms of FabZ, the crystal structures of the FabZ of Helicobacter pylori
      (HpFabZ) and its complexes with two newly discovered inhibitors have been solved.
      Different from the structures of other bacterial FabZs, HpFabZ contains an extra
      short two-turn alpha-helix (alpha4) between alpha3 and beta3, which plays an
      important role in shaping the substrate-binding tunnel. Residue Tyr-100 at the
      entrance of the tunnel adopts either an open or closed conformation in the
      crystal structure. The crystal structural characterization, the binding affinity
      determination, and the enzymatic activity assay of the HpFabZ mutant (Y100A)
      confirm the importance of Tyr-100 in catalytic activity and substrate binding.
      Residue Phe-83 at the exit tunnel was also refined in two alternative
      conformations, leading the tunnel to form an L-shape and U-shape. All these data
      thus contributed much to understanding the catalytic mechanism of HpFabZ. In
      addition, the co-crystal structures of HpFabZ with its inhibitors have suggested
      that the enzymatic activity of HpFabZ could be inhibited either by occupying the
      entrance of the tunnel or plugging the tunnel to prevent the substrate from
      accessing the active site. Our study has provided some insights into the
      catalytic and inhibitory mechanisms of FabZ, thus facilitating antibacterial
      agent development.

PMID- 18093985
TI  - The role of prostaglandin E and thromboxane-prostanoid receptors in the response
      to prostaglandin E2 in the aorta of Wistar Kyoto rats and spontaneously
      hypertensive rats.
AB  - AIMS: The present study examined the hypothesis that prostaglandin E2 (PGE2)
      through activation of prostaglandin E (EP) receptor contributes to endothelium
      dependent contractions. METHODS AND RESULTS: Western blotting revealed that the
      protein expression of EP1 receptor was significantly down-regulated in the aorta
      of the spontaneously hypertensive rat (SHR), but there was no significant
      difference in the expression of EP2, EP4, and total EP3 receptors between
      preparations of Wistar Kyoto rats (WKY) and SHR. Isometric tension studies showed
      that low concentrations of PGE2 caused endothelium-dependent relaxations in WKY
      but not in aortas of the SHR. High concentrations of PGE2 evoked contractions
      predominately through the activation of thromboxane-prostanoid (TP) receptors in
      the WKY, but involves the dual activation EP and TP receptors in the SHR.
      SQ29,548, BAYu3405 and Terutroban (TP receptor antagonists), and AH6809 (non
      selective EP receptor antagonist) abolished, while SC19220 (preferential EP1
      receptor antagonist) did not inhibit endothelium-dependent contractions. Both
      SC19220 and AH6809 significantly inhibited contractions to U46619 (TP receptor
      agonist). CONCLUSION: The present study demonstrates that the contraction caused
      by PGE2 in the SHR aorta is dependent on the activation of EP1 and TP receptors,
      but that endothelium-dependent contractions do not require the former. Thus, PGE2
      is unlikely to be an endothelium-derived contracting factor in this artery. The
      ability of AH6809 to inhibit endothelium-dependent contractions can be attributed
      to its partial antagonism at TP receptors. Nevertheless, the impairment of PGE2
      mediated relaxation may contribute to endothelial dysfunction in the aorta of the
      SHR.

PMID- 18093986
TI  - Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and
      PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis.
AB  - AIMS: Visfatin is a novel adipokine whose plasma concentrations are altered in
      obesity and obesity-related disorders; these states are associated with an
      increased incidence of cardiovascular disease. We therefore investigated the
      effect of visfatin on vascular endothelial growth factor (VEGF) and matrix
      metalloproteinases (MMP-2, MMP-9) production and the potential signalling
      cascades. METHODS AND RESULTS: In human umbilical vein endothelial cells
      (HUVECs), visfatin significantly and dose-dependently up-regulated gene
      expression and protein production of VEGF and MMPs and down-regulated expression
      of tissue inhibitors of MMPs (TIMP-1 and TIMP-2). The gelatinolytic activity of
      MMPs (analysed by zymography) correlated with mRNA and western blot findings.
      Interestingly, visfatin significantly up-regulated VEGF receptor 2 expression.
      Inhibition of VEGFR2 and VEGF [by soluble FMS-like tyrosine kinase-1 (sFlt1)]
      down-regulated visfatin-induced MMP induction. Visfatin induced dose- and time
      dependent proliferation and capillary-like tube formation. Importantly, visfatin
      was noted to have anti-apoptotic effects. In HUVECs, visfatin dose-dependently
      activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt) and ERK(1/2)
      (extracellular signal-regulated kinase) pathways. The functional effects and
      MMP/VEGF induction were shown to be dependent on the MAPK/PI3K-Akt/VEGF
      signalling pathways. Inhibition of PI3K/Akt and ERK(1/2) pathways led to
      significant decrease of visfatin-induced MMP and VEGF production and activation,
      along with significant reduction in endothelial proliferation and capillary tube
      formation. CONCLUSION: Our data provide the first evidence of visfatin-induced
      endothelial VEGF and MMP production and activity. Further, we show for the first
      time the involvement of the MAPK and PI3K/Akt signalling pathways in mediating
      these actions, as well as endothelial cell proliferation. Collectively, our
      findings provide novel insights into visfatin-induced endothelial angiogenesis.

PMID- 18093987
TI  - PARP1 is required for adhesion molecule expression in atherogenesis.
AB  - AIMS: Atherosclerosis is the leading cause of death in Western societies and a
      chronic inflammatory disease. However, the key mediators linking recruitment of
      inflammatory cells to atherogenesis remain poorly defined. Poly(ADP-ribose)
      polymerase 1 (PARP1) is a nuclear enzyme, which plays a role in acute
      inflammatory diseases. METHODS AND RESULTS: In order to test the role of PARP in
      atherogenesis, we applied chronic pharmacological PARP inhibition or genetic
      PARP1 deletion in atherosclerosis-prone apolipoprotein E-deficient mice and
      measured plaque formation, adhesion molecules, and features of plaque
      vulnerability. After 12 weeks of high-cholesterol diet, plaque formation in male
      apolipoprotein E-deficient mice was decreased by chronic inhibition of enzymatic
      PARP activity or genetic deletion of PARP1 by 46 or 51%, respectively (P < 0.05,
      n >or= 9). PARP inhibition or PARP1 deletion reduced PARP activity and diminished
      expression of inducible nitric oxide synthase, vascular cell adhesion molecule-1,
      and P- and E-selectin. Furthermore, chronic PARP inhibition reduced plaque
      macrophage (CD68) and T-cell infiltration (CD3), increased fibrous cap thickness,
      and decreased necrotic core size and cell death (P < 0.05, n >or= 6). CONCLUSION:
      Our data provide pharmacological and genetic evidence that endogenous PARP1 is
      required for atherogenesis in vivo by increasing adhesion molecules with
      endothelial activation, enhancing inflammation, and inducing features of plaque
      vulnerability. Thus, inhibition of PARP1 may represent a promising therapeutic
      target in atherosclerosis.

PMID- 18093988
TI  - Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling
      in the post-ischaemic failing rat heart.
AB  - AIMS: We investigated whether exercise training could promote angiogenesis and
      improve blood perfusion and left ventricular (LV) remodelling of the post
      myocardial infarction (MI) failing heart. We also explored the contribution of
      ameliorated beta-adrenergic receptor signalling and function on the overall
      improvement of cardiac contractility reserve induced by exercise. METHODS AND
      RESULTS: Adult Wistar male rats were randomly assigned to one of four
      experimental groups. Sham-operated and post-MI heart failure (HF) rats were
      housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise
      protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy,
      marked increase of LV diameters associated with severely impaired fractional
      shortening (14 +/- 5%), increased LV end diastolic pressure (20.9 +/- 2.6 mmHg),
      and pulmonary congestion. In addition, cardiac contractile responses to
      adrenergic stimulation were significantly blunted. In trained HF rats, exercise
      was able to (i) reactivate the cardiac vascular endothelial growth factor pathway
      with a concurrent enhancement of myocardial angiogenesis, (ii) significantly
      increase myocardial perfusion and coronary reserve, (iii) reduce cardiac
      diameters, and (iv) improve LV contractility in response to adrenergic
      stimulation. This latter finding was also associated with a significant
      improvement of cardiac beta-adrenergic receptor downregulation and
      desensitization. CONCLUSIONS: Our data indicate that exercise favourably affects
      angiogenesis and improves LV remodelling and contractility reserve in a rat model
      of severe chronic HF.

PMID- 18093989
TI  - Developmental coronary maturation is disturbed by aberrant cardiac vascular
      endothelial growth factor expression and Notch signalling.
AB  - AIMS: Currently, many potential cardiac revascularization therapies target the
      vascular endothelial growth factor (VEGF) pathway, with variable success.
      Knowledge regarding the role of the VEGF/Notch/ephrinB2 cascade in (ab)normal
      coronary development will provide information on the subtle balance of VEGF
      signalling in coronary maturation and might enhance our therapeutic
      possibilities. METHODS AND RESULTS: The effect of VEGF isoforms on coronary
      development was explored in vivo using immunohistochemistry and RT-qPCR on
      Vegf120/120 mouse embryos solely expressing VEGF120. In vitro, human arterial
      coronary endothelial cells were treated with VEGF121 or VEGF165 upon which RT
      qPCR was performed. In vivo, mutant coronary arterial endothelium showed a
      decrease in protein expression of arterial markers such as cleaved Notch1, Delta
      like4, and ephrinB2 concomitant with an increase of venous markers such as
      chicken ovalbumin upstream promoter transcription factor II. The venous
      endothelium showed the opposite effect, which was confirmed on the mRNA level. In
      vitro, mRNA expression of arterial markers highly depended on the VEGF isoform
      used, with VEGF165 having the strongest effect. Also, coronary arteriogenesis was
      anomalous in the mouse embryos with decreased arterial and increased venous
      medial development as shown by staining for smooth muscle alpha-actin, Delta
      like1, and Notch3. CONCLUSION: We demonstrate that VEGF isoform-related
      spatiotemporal cardiac alterations in the VEGF/Notch/ephrinB2 cascade lead to
      disturbed coronary development. This knowledge can contribute to optimizing
      therapies targeting VEGF signalling by enabling balancing between angiogenesis
      and vascular maturation.

PMID- 18093990
TI  - Haeme oxygenase promotes progenitor cell mobilization, neovascularization, and
      functional recovery after critical hindlimb ischaemia in mice.
AB  - AIMS: Neovascularization is an important element of long-term functional recovery
      during chronic ischaemia. We postulated that haeme oxygenase (HO) is required for
      progenitor cell recruitment, neovascularization, and blood flow recovery after
      critical hindlimb ischaemia (HLI). METHODS AND RESULTS: The femoral artery was
      ligated in FVB/N mice proximal to its superficial and deep branches. Blood flow
      in the ischaemic hindlimb was determined by laser Doppler perfusion imaging.
      Capillary density was measured by isolectin staining, and mobilization of Sca
      1(+)/Kdr(+) progenitor cells by FACS analysis. Progenitor cell recruitment to the
      ischaemic hindlimb was assessed after Tie2-lacZ transgenic bone marrow
      transplantation. Blood flow recovery after femoral artery ligation was
      significantly blunted in mice treated with the HO inhibitor tin protoporphyrin-IX
      (25 mg/kg i.p., every other day). HO-inhibited mice developed more pronounced
      limb necrosis, associated with impaired hindlimb motor function. Capillary
      density in the ischaemic hindlimb and mobilization of Sca-1(+)/Kdr(+) progenitor
      cells were significantly reduced after HO inhibition. After transplantation of
      Tie2-lacZ transgenic bone marrow cells into lethally irradiated wild-type mice,
      fewer LacZ(+) cells were detected in the ischaemic hindlimb muscle of HO
      inhibited mice. Mechanistically, HO inhibition prevented the establishment of a
      stromal cell-derived factor-1 gradient for progenitor cell mobilization between
      the ischaemic hindlimb and bone marrow. CONCLUSION: HOs are required for
      progenitor cell recruitment, neovascularization, and functional recovery after
      HLI.

PMID- 18093991
TI  - Laboratory evolution of P450 BM3 for mediated electron transfer yielding an
      activity-improved and reductase-independent variant.
AB  - One of the main obstacles in employing P450 monooxygenases for preparative
      chemical syntheses in cell-free systems is their requirement for cofactors such
      as NAD(P)H. In order to engineer P450 BM3 from Bacillus megaterium for cost
      effective process conditions in vitro, a validated medium throughput screening
      system based on cheap Zn dust as an electron source and Cobalt(III)sepulchrate
      (Co(III)sep) as a mediator was reported. In the current study, the alternative
      cofactor system Zn/Co(III)sep was used in a directed evolution experiment to
      improve the Co(III)sep-mediated electron transfer to P450 BM3. A variant,
      carrying five mutations (R47F F87A V281G M354S D363H, Table I), P450 BM3 M5 was
      identified and characterized with respect to its kinetic parameters. P450 BM3 M5
      achieved for mediated electron transfer a 2-fold higher k(cat) value and a 3-fold
      higher catalytic efficiency compared with the starting point mutant P450 BM3 F87A
      (k(cat): 62 min(-1) compared with 28 min(-1); k(cat)/K(m): 62 microM(-1)min(-1)
      compared to 19 microM(-1)min(-1)). For obtaining first insights on electron
      transfer contributions, three reductase-deficient variants were generated. The
      reductase-deficient mutant of P450 BMP M5 exhibited a catalytic efficiency of 69%
      and a k(cat) value of 89% of the values obtained for P450 BM3 M5.

PMID- 18093992
TI  - A new expression system for protein crystallization using trimeric coiled-coil
      adaptors.
AB  - We repeatedly experienced difficulties in obtaining pure protein of a defined
      oligomeric state when expressing domains that consist partially or entirely of
      coiled coils. We therefore modified an established expression vector, pASK-IBA,
      to generate N- and C-terminal fusions of the cloned domain in heptad register
      with the GCN4 leucine zipper. GCN4 is a well-characterized coiled coil, for which
      stable dimeric, trimeric and tetrameric forms exist. To test this expression
      system, we produced a series of constructs derived from the trimeric
      autotransporter adhesin STM3691 of Salmonella (SadA), which has a highly
      repetitive structure punctuated by coiled-coil regions. The constructs begin and
      end with predicted coiled-coil segments of SadA, each fused in the correct heptad
      register to the trimeric form of GCN4, GCN4pII. All constructs were expressed at
      high levels, trimerized either natively or after refolding from inclusion bodies,
      and yielded crystals that diffracted to high resolution. Thus, fusion to GCN4pII
      allows for the efficient expression and crystallization of proteins containing
      trimeric coiled coils. The structure of short constructs can be solved
      conveniently by molecular replacement using the known GCN4 structure as a search
      model. The system can be adapted for constructs with dimeric or tetrameric coiled
      coils, using the corresponding GCN4 variants.

PMID- 18093993
TI  - An adaptive mutation in adenylate kinase that increases organismal fitness is
      linked to stability-activity trade-offs.
AB  - Protein function is a balance between activity and stability. However, the
      relevance of stability-activity trade-offs for protein evolution and their impact
      on organismal fitness have been difficult to determine. Previously, we have
      linked organismal survival at increasing temperatures to adaptive changes to a
      single protein sequence through allelic replacement of an essential gene,
      adenylate kinase (adk), in a thermophile. In vivo continuous evolution of the
      temperature-sensitive thermophile has shown that the first step toward increased
      organismal fitness is mutation of glutamine-199 to arginine in the mesophilic
      enzyme (AKsub Q199R). Here, we show that although substitution of Arg-199 did
      confer a modest increase in stability (0.6 kcal mol(-1)at 20 degrees C; DeltaT(m)
      = 3.0 degrees C), it is a large change in the activity profile of the enzyme that
      is responsible for its exceptional robustness during the earlier experimental
      evolution study. Kinetic studies of AKsub Q199R show that it has a strong loss of
      enzymatic activity (>50%) at lower temperatures (20-45 degrees C) and a
      subsequent increase at elevated temperatures. The stability-activity trade-off
      observed for AKsub Q199R was linked to the rigidification of the overall
      structure through stabilization of a polypeptide loop containing Arg-199 that is
      part of the ATP-binding site of the enzyme. Structural analysis revealed the
      formation of new ionic interactions facilitated by Arg-199. Our results suggest
      that stability-activity trade-offs are employed readily as an evolutionary
      strategy during natural selection to increase organismal fitness.

PMID- 18093994
TI  - Metabolic symbiosis and the birth of the plant kingdom.
AB  - Eukaryotic cells are composed of a variety of membrane-bound organelles that are
      thought to derive from symbiotic associations involving bacteria, archaea, or
      other eukaryotes. In addition to acquiring the plastid, all Archaeplastida and
      some of their endosymbiotic derivatives can be distinguished from other organisms
      by the fact that they accumulate starch, a semicrystalline-storage polysaccharide
      distantly related to glycogen and never found elsewhere. We now provide the first
      evidence for the existence of starch in a particular species of single-cell
      diazotrophic cyanobacterium. We provide evidence for the existence in the
      eukaryotic host cell at the time of primary endosymbiosis of an uridine
      diphosphoglucose (UDP-glucose)-based pathway similar to that characterized in
      amoebas. Because of the monophyletic origin of plants, we can define the genetic
      makeup of the Archaeplastida ancestor with respect to storage polysaccharide
      metabolism. The most likely enzyme-partitioning scenario between the plastid's
      ancestor and its eukaryotic host immediately suggests the precise nature of the
      ancient metabolic symbiotic relationship. The latter consisted in the export of
      adenosine diphosphoglucose (ADP-glucose) from the cyanobiont in exchange for the
      import of reduced nitrogen from the host. We further speculate that the
      monophyletic origin of plastids may lie in an organism with close relatedness to
      present-day group V cyanobacteria.

PMID- 18093995
TI  - Contrasting signatures of population growth for mitochondrial DNA and Y
      chromosomes among human populations in Africa.
AB  - A history of Pleistocene population expansion has been inferred from the
      frequency spectrum of polymorphism in the mitochondrial DNA (mtDNA) of many human
      populations. Similar patterns are not typically observed for autosomal and X
      linked loci. One explanation for this discrepancy is a recent population
      bottleneck, with different rates of recovery for haploid and autosomal loci as a
      result of their different effective population sizes. This hypothesis predicts
      that mitochondrial and Y chromosomal DNA will show a similar skew in the
      frequency spectrum in populations that have experienced a recent increase in
      effective population size. We test this hypothesis by resequencing 6.6 kb of
      noncoding Y chromosomal DNA and 780 basepairs of the mtDNA cytochrome c oxidase
      subunit III (COIII) gene in 172 males from 5 African populations. Four tests of
      population expansion are employed for each locus in each population: Fu's Fs
      statistic, the R(2) statistic, coalescent simulations, and the mismatch
      distribution. Consistent with previous results, patterns of mtDNA polymorphism
      better fit a model of constant population size for food-gathering populations and
      a model of population expansion for food-producing populations. In contrast, none
      of the tests reveal evidence of Y chromosome growth for either food-gatherers or
      food-producers. The distinct mtDNA and Y chromosome polymorphism patterns most
      likely reflect sex-biased demographic processes in the recent history of African
      populations. We hypothesize that males experienced smaller effective population
      sizes and/or lower rates of migration during the Bantu expansion, which occurred
      over the last 5,000 years.

PMID- 18093996
TI  - mtDNA variation predicts population size in humans and reveals a major Southern
      Asian chapter in human prehistory.
AB  - The relative timing and size of regional human population growth following our
      expansion from Africa remain unknown. Human mitochondrial DNA (mtDNA) diversity
      carries a legacy of our population history. Given a set of sequences, we can use
      coalescent theory to estimate past population size through time and draw
      inferences about human population history. However, recent work has challenged
      the validity of using mtDNA diversity to infer species population sizes. Here we
      use Bayesian coalescent inference methods, together with a global data set of 357
      human mtDNA coding-region sequences, to infer human population sizes through time
      across 8 major geographic regions. Our estimates of relative population sizes
      show remarkable concordance with the contemporary regional distribution of humans
      across Africa, Eurasia, and the Americas, indicating that mtDNA diversity is a
      good predictor of population size in humans. Plots of population size through
      time show slow growth in sub-Saharan Africa beginning 143-193 kya, followed by a
      rapid expansion into Eurasia after the emergence of the first non-African mtDNA
      lineages 50-70 kya. Outside Africa, the earliest and fastest growth is inferred
      in Southern Asia approximately 52 kya, followed by a succession of growth phases
      in Northern and Central Asia (approximately 49 kya), Australia (approximately 48
      kya), Europe (approximately 42 kya), the Middle East and North Africa
      (approximately 40 kya), New Guinea (approximately 39 kya), the Americas
      (approximately 18 kya), and a second expansion in Europe (approximately 10-15
      kya). Comparisons of relative regional population sizes through time suggest that
      between approximately 45 and 20 kya most of humanity lived in Southern Asia.
      These findings not only support the use of mtDNA data for estimating human
      population size but also provide a unique picture of human prehistory and
      demonstrate the importance of Southern Asia to our recent evolutionary past.

PMID- 18094000
TI  - Clinical identification and treatment of a rapidly progressing disease state in
      patients with rheumatoid arthritis.
AB  - Inflammation is the major factor driving the progression of structural damage in
      rheumatoid arthritis (RA); therefore, it is critical to achieve rapid suppression
      of inflammation to maximize disease control. The severity of inflammation and
      progression of joint damage varies from patient to patient. Some patients have
      the propensity to change slowly over time and then progress in a more rapid and
      dynamic fashion. In those where inflammation is more severe, extensive damage can
      occur within only a few years of disease onset. The progress of joint
      destruction, as assessed radiographically, results in a decline in functional
      capacity and quality of life. Consequently, the challenge for clinicians is to
      identify and treat those patients who develop rapid, progressive disease. Several
      biological markers and clinical indicators have been identified to help predict
      or establish which of the patients have rapidly progressing disease or who are at
      most risk for rapid progression. Early diagnosis of patients with rapidly
      progressing RA enables immediate and intensive intervention (e.g. with biologic
      therapy) and a greater opportunity to change the course of disease.

PMID- 18094001
TI  - Effects of immunosuppressive treatment on microsomal prostaglandin E synthase 1
      and cyclooxygenases expression in muscle tissue of patients with polymyositis or
      dermatomyositis.
AB  - OBJECTIVES: To investigate the expression of microsomal prostaglandin E (PGE)
      synthase 1 (mPGES-1) and cyclooxygenase (COX) in muscle biopsies from patients
      with polymyositis or dermatomyositis before and after conventional
      immunosuppressive treatment. METHODS: mPGES-1 and COX expression was evaluated by
      immunohistochemistry in muscle tissue from healthy individuals and from patients
      with polymyositis or dermatomyositis before and after conventional
      immunosuppressive treatment. The number of inflammatory cell infiltrates, T
      lymphocytes and macrophages was estimated before and after treatment. To localise
      the mPGES-1 expression double immunofluorescence was performed with antibodies
      against mPGES-1, CD3, CD68, CD163 and a fibroblast marker. A functional index was
      used to assess muscle function. RESULTS: In patients with myositis, mPGES-1, COX
      2 and COX-1 expression was significantly higher compared to healthy individuals
      and associated with inflammatory cells. Double immunofluorescence demonstrated a
      predominant expression of mPGES-1 in macrophages. Conventional immunosuppressive
      treatment resulted in improved but still lower muscle function than normal. A
      decreased number of CD68-positive macrophages and reduced COX-2 expression in
      muscle tissue was also seen. By contrast, following the same treatment no
      significant changes were observed in muscle tissue regarding number of
      infiltrates, T lymphocytes, CD163-positive macrophages or mPGES-1 protein levels.
      CONCLUSIONS: Increased expression of mPGES-1, COX-1 and COX-2 at protein level
      was observed in muscle tissue from patients with myositis compared to healthy
      individuals. Conventional immunosuppressive treatment led to a significant
      downregulation of COX-2 in myositis muscle tissue. However, the expression of
      mPGES-1 and COX-1 remained unchanged indicating a role of these enzymes in the
      chronicity of these diseases.

PMID- 18094003
TI  - Australian pension funds and tobacco investments: promoting ill health and out-of
      step with their members.
AB  - There has been no systematic examination of issues surrounding pension funds and
      their tobacco shareholdings. This paper describes two studies designed to
      document the tobacco investment policies and practices of pension funds, and to
      assess community and fund member attitudes to pension fund shareholdings in the
      tobacco industry. Chief executives (n = 282) of Australian pension funds were
      mailed questionnaires. Of 241 eligible funds, 107 (44.4%) returned
      questionnaires, representing about 61% of total Australian primary superannuation
      accounts. Twelve percent indicated that they did not currently hold tobacco
      investments, 30% held tobacco shares and 58% did not know or failed to answer.
      Overall, 6% of respondents said that they held no tobacco investments and would
      not consider future investments; 2% had formal policies precluding tobacco
      investments. Funds with 10,000 or more members were more likely (p = 0.0006) to
      report tobacco investments. External fund manager advice was the most important
      factor influencing the funds' position. In the second study, a one-third random
      sub-sample of consenting subjects from 12,000 households randomly selected from
      the New South Wales Electronic White Pages completed phone interviews. From 7141
      eligible households, 3503 (49.1%) subjects consented. One-third (n = 1158) were
      asked the pension fund questions. Over three-quarters (77.4%) of all respondents
      disagreed that pension fund investments in tobacco were ethical. Approximately
      two-thirds (63.6%) of fund members (n = 852) agreed that their funds should not
      make tobacco investments. There were three statistically significant predictors
      of opposition to such investments: being female, more highly educated and non
      smoking status. Nearly all pension funds treat tobacco investments like any other
      investment. In contrast, most of the public including fund members are strongly
      opposed to such investments. Suggestions for public health advocacy strategies to
      reduce the negative health promotion effects of pension funds in this area are
      outlined.

PMID- 18094002
TI  - Amelioration of human lupus-like phenotypes in MRL/lpr mice by overexpression of
      interleukin 27 receptor alpha (WSX-1).
AB  - OBJECTIVE: In the present work, we investigate the role of interleukin
      (IL)27/IL27 receptor alpha (Ralpha) (WSX-1) in the development of autoimmune
      disorders in the MRL/lpr mouse, which is considered as an experimental model of
      systemic lupus erythaematosus (SLE) in humans. METHODS: We generated two strains
      of WSX-1 transgenic mice in the MRL/lpr background with different expression
      levels of WSX-1, and investigated the effect of WSX-1 overexpression on survival,
      glomerulonephritis and immunological properties. RESULTS: In comparison with wild
      type (WT) MRL/lpr and transgenic (Tg) low (TgL) mice, Tg high (TgH) mice
      exhibited a prolonged lifespan and no apparent development of autoimmune
      nephritis. Production of anti-dsDNA antibody and total IgG and IgG2a were
      significantly lower in TgH mice than those of TgL and WT mice. The expressed
      amounts of interferon (IFN)gamma and IL4 mRNA by CD4+ T cells from Tg mice
      decreased in a dose-dependent fashion. CD4+ splenic lymphocytes in TgH mice were
      more subject to the IL27-mediated suppression of cytokine production. In vitro
      stimulation of CD4+ T cells by IL27 resulted in over phosphorylation of STAT3 in
      TgH cells than in WT cells. CONCLUSION: WSX-1 overexpression in the MRL/lpr
      background rendered the autoimmune prone mice protected from the development of
      autoimmune diseases. Our results suggest that IL27 signalling may be a
      therapeutic target against autoimmune diseases, including human SLE.

PMID- 18094004
TI  - Mast cell-derived tumour necrosis factor is essential for allergic airway
      disease.
AB  - Mast cells are thought to contribute to allergic airway disease. However, the
      role of mast cell-produced mediators, such as tumour necrosis factor (TNF), for
      the development of allergic airway disease is unclear. In order to define the
      role of mast cells in acute allergic airway disease two strains of mast cell
      deficient mice (Kit(W/Wv) and Kit(W-sh/W-sh)) were studied. Compared with their
      wild-type littermates, Kit(W/Wv) and Kit(W-sh/W-sh) mice developed significantly
      lower airway responsiveness to methacholine and less airway inflammation and
      goblet cell metaplasia, following sensitisation in the absence of adjuvant and
      airway challenge. Transfer of bone marrow-derived mast cells (BMMCs) from wild
      type mice to Kit(W-sh/W-sh) mice reconstituted both airway responsiveness and
      inflammation to levels similar to those in sensitised and challenged wild-type
      mice. In contrast, sensitised Kit(W-sh/W-sh) mice reconstituted with BMMCs from
      TNF-deficient mice were still severely impaired in their ability to develop
      airway hyperresponsiveness, inflammation or goblet cell metaplasia following
      allergen challenge. The present results demonstrate the significance of mast
      cells in the development of airway disease and highlight the importance of mast
      cell-derived tumour necrosis factor in these responses.

PMID- 18094005
TI  - Lung carcinomas with a basaloid pattern: a study of 90 cases focusing on their
      poor prognosis.
AB  - Lung carcinoma with a basaloid pattern (BC) is classified as either a basaloid
      variant of squamous cell carcinoma (SCC) or as variant of large cell carcinoma
      (LCC) depending on the presence of a squamous component. In a previous study of
      37 cases, the present authors showed that BC presented with a shorter median and
      overall survival. In order to confirm its clinical significance in a larger
      series, 90 BC, including 46 basaloid variants of LCC and 44 basaloid variants of
      SCC, were compared with 1,328 other nonsmall cell lung carcinoma (NSCLC) with
      regard to clinical features and survival. The survival of basaloid variants of
      LCC and SCC was comparable. Median and overall survival were significantly lower
      for BC than for NSCLC in stage I-II patients, with a median survival of 29 and 49
      months, respectively, and 5-yr survival rates of 27 and 44% for BC and NSCLC.
      When disease-specific survival was considered, BC had a shorter survival than
      both NSCLC and SCC. Basaloid pattern confers a poor prognosis in nonsmall cell
      lung carcinoma, especially in stage I-II patients, suggesting that lung carcinoma
      with a basaloid pattern is not only a variant of squamous cell carcinoma or large
      cell carcinoma, but is a unique entity with a significantly poor prognosis.

PMID- 18094006
TI  - Standardised PCR-based molecular epidemiology of tuberculosis.
AB  - A population-based molecular epidemiology investigation has been undertaken to
      evaluate tuberculosis transmission and control in the Brussels-Capital Region
      (Belgium). All tuberculosis cases reported from January 2003 to December 2004
      were investigated. In total, 536 Mycobacterium tuberculosis isolates (89% of
      culture-positive samples) were genotyped by the newly standardised 24 loci-based
      mycobacterial interspersed repetitive unit-variable number tandem-repeat typing,
      spoligotyping and IS6110 fingerprinting. Of all the patients, 30% were grouped
      based on strain clusters, suggesting a transmission index of 20%. An unsuspected
      outbreak entailing > or = 23 patients was evidenced by molecular typing analysis
      and confirmed by contact tracing. Foreign-born status accounted for 79% of the
      studied patients, including 37.9% illegal immigrants and asylum seekers. Among
      foreign-born patients, asylum seekers and illegal immigrants were significantly
      less abundant in strain clusters than settled residents. Tuberculosis in the
      Brussels-Capital Region is a bi-faceted problem, comprising both persisting
      recent transmission and "imported diseases". Molecular epidemiology based on real
      time genotyping techniques has proven invaluable in better understanding
      tuberculosis transmission. However, it will most efficiently contribute to
      tuberculosis control when implemented in an integrated public health system.

PMID- 18094007
TI  - The plasma ammonia response to cycle exercise in COPD.
AB  - The plasma ammonia response to exercise in chronic obstructive pulmonary disease
      (COPD) was examined and the relationship between plasma ammonia concentration and
      muscle adenine nucleotide metabolism was explored. In total, 25 stable COPD
      patients and 13 similar-aged controls underwent incremental and constant-work
      rate cycle exercise tests. Arterialised venous blood was sampled at rest, at 1
      min intervals during exercise and <or=5 min after exercise for ammonia and
      lactate concentration. Peak incremental work rate was significantly less in COPD
      subjects (67+/-21 W) than similar-aged controls (156+/-46 W). In COPD and control
      subjects, plasma ammonia concentration increased during incremental exercise
      until 2 min post-exercise and then declined by 5 min post-exercise. However, two
      distinct patterns were seen in COPD subjects. In one group (n = 16), ammonia
      increased (42.8+/-3.3 micromol x L(-1)) by a similar magnitude as the controls
      (55.5+/-7.0 micromol x L(-1)). In the second COPD group (n = 9), no ammonia
      increase was observed despite a similar lactate increase. Ammonia change with
      incremental and constant-work rate exercise strongly correlated in COPD subjects.
      Plasma ammonia increase correlated with muscle inosine-5'-monophosphate formation
      after constant-work rate exercise. Plasma ammonia concentration increases during
      incremental and constant-work rate cycle exercise in chronic obstructive
      pulmonary disease subjects at lower absolute work rates compared with similar
      aged controls. The plasma ammonia response may provide useful information about
      adenine nucleotide metabolism and, therefore, muscle fatigue during exercise in
      patients with chronic obstructive pulmonary disease.

PMID- 18094008
TI  - Enhancement of neutrophil function by the bronchial epithelium stimulated by
      epidermal growth factor.
AB  - The bronchial epithelium is an important physical barrier that regulates
      physiological processes including leukocyte trafficking. The aim of the present
      study was to elucidate the mechanisms whereby the bronchial epithelium,
      stimulated by epidermal growth factor (EGF) as part of a response to acute or
      chronic injury, could activate and chemoattract human neutrophils. Subconfluent
      human bronchial epithelial (16HBE) cells were stimulated with EGF to mimic the in
      vivo events after injury. The effect of the resulting EGF-conditioned media (CM)
      was compared with that of basal-CM with respect to neutrophil activation and
      chemotaxis. Such findings were then confirmed using primary bronchial epithelial
      cells (PBECs) from healthy volunteers. EGF-CM from 16HBE cells caused increased
      expression of CD11b/CD66b and CD62L loss on neutrophils when compared with basal
      CM. EGF-CM contained significant neutrophil chemotactic activity involving
      granulocyte-macrophage colony-stimulating factor and interleukin-8 that was
      potentiated by leukotriene B(4). This was dependent on neutrophil
      phosphatidylinositol-3-kinase activation and Akt phosphorylation, with partial
      regulation by phospholipase D, but not mammalian target of rapamycin. Consistent
      with these observations, EGF-CM derived from PBECs displayed increased
      chemotactic activity. The present results suggest that the enhanced chemotactic
      activity of the epidermal growth factor-conditioned epithelium can enhance
      neutrophil-mediated immunity during acute injury, while during continued injury
      and repair, as in chronic asthma, this could contribute to persistent
      neutrophilic inflammation.

PMID- 18094009
TI  - Sildenafil treatment in COPD does not affect stroke volume or exercise capacity.
AB  - In chronic obstructive pulmonary disease (COPD) patients, stroke volume response
      to exercise is impaired. The aim of the present study was to investigate whether
      3 months of sildenafil treatment improves stroke volume and, if so, whether this
      improvement is related to the pulmonary artery pressure and translated into an
      improved exercise capacity. A total of 15 stable COPD patients (Global Initiative
      for Chronic Obstructive Lung Disease stage II-IV) underwent right heart
      catheterisation at rest and during exercise. Stroke volume was assessed by
      magnetic resonance imaging (MRI) at rest and during submaximal exercise in the
      supine position and compared with eight age-matched controls. Additionally, a
      cardiopulmonary exercise test and a 6-min walking distance test were performed.
      Exercise tests and MRI were repeated after 12 weeks of oral therapy with 50 mg
      sildenafil three times daily. Stroke volume in COPD patients was significantly
      lower than in healthy controls (62+/-12 versus 81+/-22 mL at rest and 70+/-15
      versus 101+/-28 mL during exercise). Pulmonary hypertension (PH) was diagnosed in
      nine patients and was absent in six. Treatment with sildenafil had no effect on
      stroke volume or exercise capacity. Although the stroke volume was lower in COPD
      patients with associated PH in comparison with non-PH patients, there was no
      difference in treatment response between both groups. In the present group of 15
      chronic obstructive pulmonary disease patients, a reduced stroke volume was found
      at rest and during exercise. Neither stroke volume nor exercise capacity were
      improved by 3 months of sildenafil therapy.

PMID- 18094010
TI  - Troponin I and risk stratification of patients with acute nonmassive pulmonary
      embolism.
AB  - The assessment of risk and appropriate treatment of patients with acute pulmonary
      embolism (PE) remains a challenge. The prognostic performance of cardiac troponin
      I (cTnI) in predicting 30-day all-cause mortality was prospectively assessed in
      consecutive haemodynamically stable patients with PE. The present study included
      318 haemodynamically stable patients with PE. During the 30-day study period, 23
      (7%) patients died. cTnI was elevated (>or=0.1 ng x mL(-1)) in 102 (32%)
      patients. An age >65 yrs, systolic blood pressure <120 mmHg and severity of
      illness assessed using the PE severity index (PESI) were significantly associated
      with an increased risk for mortality, but no significant association was found
      between elevation of cTnI and 30-day mortality in a logistic regression analysis.
      When only fatal PE was considered, multivariate analysis showed that severity of
      illness using the PESI and an elevated cTnI (odds ratio 3.7, 95% confidence
      interval (CI) 1.1-12.8) were associated with a significant increase in the risk
      for death. The negative predictive value (95% CI) of a negative cTnI for
      mortality was 93 (90-97)%. In conclusion, in haemodynamically stable patients
      with acute pulmonary embolism, cardiac troponin I was not an independent
      predictor of 30-day all-cause mortality, although it did predict fatal pulmonary
      embolism.

PMID- 18094011
TI  - Effectiveness of pharmacist intervention for asthma control improvement.
AB  - Education on optimal medication use is an essential strategy to improve asthma
      control. The current authors investigated whether pharmacist interventions,
      focused on appropriate use of asthma medication and tailor-made to the patient's
      current asthma control, would improve asthma control in adult patients. A 6-month
      randomised, controlled, parallel-group trial was conducted in 66 community
      pharmacies in Belgium. Patients were randomly assigned to receive usual
      pharmacist care (n = 94) or a pre-defined pharmacist intervention (n = 107). This
      intervention mainly focused on improving inhalation technique and medication
      adherence. Primary outcome was the level of asthma control, as assessed by the
      Asthma Control Test (ACT). Mean ACT scores did not change from baseline for both
      study groups. However, a pre-defined subgroup analysis of patients having
      insufficiently controlled asthma at baseline showed that the intervention had
      significantly increased the ACT score after 6 months compared with usual care.
      The intervention also reduced, for the complete study group, reliever medication
      use and the frequency of night-time awakenings due to asthma. Inhalation
      technique and adherence to controller medication were significantly better in the
      intervention group. In conclusion, pragmatic community pharmacy-based programmes
      can significantly improve therapeutic outcomes in adult asthma patients.

PMID- 18094012
TI  - A small-molecule compound targeting CCR5 and CXCR3 prevents airway
      hyperresponsiveness and inflammation.
AB  - Asthma is associated with increased numbers of T-cells in the lung. CC chemokine
      receptor (CCR)5 and CXC chemokine receptor (CXCR)3 have been reported to play
      important roles in the lung T-cell homing pathway, and may be potential targets
      for asthma therapy. The aim of the present study was to investigate the role of
      CCR5 and CXCR3 in allergen-induced acute asthma and to determine whether a novel
      small-molecule compound, TAK-779, targeting CCR5 and CXCR3 can attenuate allergic
      airway responses. Mice were sensitised with ovalbumin (OVA). mRNA expression of
      chemokine receptors in the lung were measured after the challenge with either
      aerosolised phosphate-buffered saline or OVA. OVA-sensitised mice were also
      treated with TAK-779. Respiratory function was measured, bronchoalveolar lavage
      was performed, and blood and lung samples were obtained. OVA challenge increased
      CCR3, CCR5 and CXCR3 expression in the lung. Treatment with TAK-779 significantly
      attenuated altered respiratory function and pulmonary allergic inflammation. The
      beneficial effect was associated with reduced expression of CCR5 and CXCR3 in the
      lung. These data demonstrate that blockade of CC chemokine receptor 5 and CXC
      chemokine receptor 3 using TAK-779, a synthetic nonpeptide compound, can prevent
      the development of asthma features in a mouse model. Thus, CC chemokine receptor
      5 and CXC chemokine receptor 3 may be potential targets for asthma therapy.

PMID- 18094013
TI  - Effect of growth hormone therapy on nitric oxide formation in cystic fibrosis
      patients.
AB  - Airway nitric oxide production is decreased in cystic fibrosis. As growth hormone
      therapy has been shown to increase nitric oxide production in growth hormone
      deficient patients, it may also affect nitric oxide production in patients with
      cystic fibrosis. The objective of the present study was to investigate the effect
      of growth hormone therapy on systemic and airway nitric oxide formation in
      patients with cystic fibrosis. Nitric oxide metabolites in serum and urine, amino
      acid concentrations in serum and sputum, as well as exhaled nitric oxide, were
      measured in children with cystic fibrosis before, during and after 1 yr of
      treatment with human growth hormone. Nitric oxide metabolite concentrations
      increased significantly in serum and urine during the treatment period. Serum
      amino acid concentrations (including l-arginine, the substrate for nitric oxide
      synthases) also increased during treatment. The systemic bioavailability of l
      arginine for nitric oxide synthases, expressed as ratio of l-arginine/l
      ornithine+lysine, remained unchanged. In contrast, l-arginine concentrations in
      sputum decreased significantly during growth hormone treatment, as did exhaled
      nitric oxide levels. Treatment with growth hormone in children with cystic
      fibrosis decreases exhaled nitric oxide by reducing the concentration of l
      arginine in the airways.

PMID- 18094014
TI  - Pseudomonas aeruginosa in the home environment of newly infected cystic fibrosis
      patients.
AB  - The source of acquisition of Pseudomonas aeruginosa in cystic fibrosis (CF)
      patients remains unknown. Patient-to-patient transmission has been well
      documented but the role of the environment as a source of initial infection is as
      yet unclear. In the present study, the origin of the first P. aeruginosa isolate
      in CF patients was investigated by comparing the P. aeruginosa genotype(s) from
      newly infected patients with genotypes of P. aeruginosa isolates from the home
      environment and from other patients from the same CF centre. A total of 50 newly
      infected patients were studied. P. aeruginosa could be cultured from 5.9% of the
      environmental samples, corresponding to 18 patients. For nine of these, the
      genotype of the environmental P. aeruginosa isolate was identical to the
      patient's isolate. In total, 72% of the environmental P. aeruginosa isolates were
      encountered in the bathroom. Patient-to-patient transmission within the CF centre
      could not be ruled out for three patients. In summary, a low prevalence of
      Pseudomonas aeruginosa was found in the home environment of the newly infected
      cystic fibrosis patients. The bathroom should be targeted in any preventive
      cleaning procedures. An environmental source of the new infection could not be
      ruled out in nine patients.

PMID- 18094015
TI  - Phosphodiesterase-4 inhibition attenuates pulmonary inflammation in neonatal lung
      injury.
AB  - Phosphodiesterase-4 (PDE4) inhibitors may offer novel therapeutic strategies in
      respiratory diseases, including asthma and chronic obstructive pulmonary disease.
      Therefore, selective PDE4 inhibitors may also provide a therapeutic option for
      very pre-term infants with bronchopulmonary dysplasia (BPD). The anti
      inflammatory effect of two PDE4 inhibitors was investigated in a pre-term rat
      model of hyperoxia-induced lung injury. Pre-term rat pups were exposed to room
      air, hyperoxia, or hyperoxia and one of two PDE4 inhibitors: rolipram and
      piclamilast. The anti-inflammatory effects of prolonged PDE4 inhibitor therapy
      were investigated by studying survival, histopathology, fibrin deposition,
      alveolar vascular leakage and differential mRNA expression (real-time RT-PCR) of
      key genes involved in inflammation, alveolar enlargement, coagulation and
      fibrinolysis. PDE4 inhibitor therapy prolonged median survival by up to 7 days
      and reduced alveolar fibrin deposition, lung inflammation and vascular leakage by
      decreasing the influx of monocytes and macrophages and protein efflux in
      bronchoalveolar lavage fluid. Analysis of mRNA expression of key genes involved
      in experimental BPD revealed a significant PDE4 inhibitor-induced improvement of
      genes involved in inflammation, fibrin deposition and alveolarisation. In
      conclusion, phosphodiesterase-4 inhibition prolongs survival by inhibiting
      inflammation and reducing alveolar fibrin deposition in pre-term rat pups with
      neonatal hyperoxic lung injury, whereby piclamilast outperformed rolipram.

PMID- 18094016
TI  - Cancer incidence rates among South Asians in four geographic regions: India,
      Singapore, UK and US.
AB  - BACKGROUND: Data are limited regarding cancer incidence among Indians residing in
      different geographic regions around the world. Examining such rates may provide
      us with insights into future aetiological research possibilities as well as
      screening and prevention. METHODS: Incidence rates for all cancers combined and
      19 specific cancers were obtained for India from Globocan 2002, for Indians in
      Singapore from Cancer Incidence in Five Continents (VIII), and from national data
      sources for South Asians (SA) in the United Kingdom (UK) and for Asian
      Indians/Pakistanis (AIP) and whites in the United States (US). RESULTS: We
      observed the lowest total cancer incidence rates in India (111 and 116 per
      100,000 among males and females, respectively, age-standardized to the 1960 world
      population) and the highest among US whites (362 and 296). Cancer incidence rates
      among Indians residing outside of India were: intermediate Singapore (102 and
      132), UK (173 and 179) and US ranges 152-176 and 142-164. A similar pattern was
      observed for cancers of the colorectum, prostate, thyroid, pancreas, lung, breast
      and non-Hodgkin lymphoma. In contrast, rates for cancers of the oral cavity,
      oesophagus, larynx and cervix uteri were highest in India. Although little
      geographic variability was apparent for stomach cancer incidence, Indians in
      Singapore had the highest rates compared with any other region. The UK SA and the
      US AIP appear with adopt the cancer patterns of their host country. CONCLUSION:
      Variations in environmental exposures such as tobacco use, diet and infection, as
      well as better health care access and knowledge may explain some of the observed
      incidence differences.

PMID- 18094017
TI  - Feasibility of high activity rhenium-188-microsphere in hepatic
      radioembolization.
AB  - BACKGROUND: This paper describes the feasibility of intra-arterial high-activity
      administration of (188)Re-microspheres. METHODS: Patients with unresectable
      colorectal liver metastases or hepatocellular cancer (HCC) received single
      treatments with (188)Re-microspheres. The administered activity was calculated to
      give a liver dose of 100 Gy. From post-therapeutic scans and urine sampling, the
      dose to the liver, metastases and bladder was calculated. Toxicity was assessed
      up to 3 months after administration by means of the Common Terminology Criteria
      for Adverse Events v3.0 (Trotti et al. CTCAE v3.0: development of a comprehensive
      grading system for the adverse effects of cancer treatment. Semin Radiat Oncol
      2003;13(3):176-81). Response was evaluated on CT. RESULTS: 13.6 +/- 4.7 GBq
      (188)Re-microspheres was administered selective in the feeding artery of the
      tumour to 10 patients (3 x HCC and 7 x colorectal liver metastases). There was a
      low urinary excretion rate of 8.9 +/- 3.8% of administered activity within 96 h.
      The absorbed dose to the tumour, normal liver (excluding the tumour) and bladder
      was 10.24 +/- 5.02 Gy/GBq (128 +/- 47 Gy), 3.94 +/- 2.52 Gy/GBq (50 +/- 33 Gy)
      and 0.27 +/- 0.20 Gy/GBq (2.4 +/- 1.9 Gy), respectively. There was an acceptable
      rate of toxicity in 30% of grades I and II, respectively, and 10% with grade III.
      There was reversible in the most patients within 14 days after treatment. The
      response was assessed on CT: two patients had a partial response (PR), five
      patients had stable disease and three patients had disease progression.
      CONCLUSION: Treatment of colorectal liver metastases or HCC using high activities
      of (188)Re-microspheres was well tolerated and a PR was seen in 2 of 10 patients.
      The treatment represents a therapeutic option in these patients.

PMID- 18094018
TI  - Electrocardiographic evidence of ventricular repolarization remodelling during
      atrial fibrillation.
AB  - AIMS: Some atrial fibrillation (AF) patients develop excessive QTc prolongation
      and torsade de pointes when they take QTc-prolonging antiarrhythmic drugs (class
      IA/III) immediately after termination of AF. We hypothesized that this is caused
      by changes in ventricular repolarization during AF. We aimed to establish whether
      such 'ventricular repolarization remodelling' occurs. METHODS AND RESULTS: We
      studied all patients who visited our cardiac emergency room with AF and converted
      to sinus rhythm (SR) in a 30 months' period. We defined four groups: (i) no
      antiarrhythmic drugs, electrical cardioversion (n = 30), (ii) no antiarrhythmic
      drugs, spontaneous AF termination (n = 19), (iii) antiarrhythmic drugs,
      electrical cardioversion (n = 29), and (iv) antiarrhythmic drugs, spontaneous AF
      termination (n = 9). We studied QTc duration at SR before AF (SR(baseline)),
      immediately after termination of AF (SR(postAF)), and at follow-up (SR(followup):
      > or =7 days after SR(postAF)). Moreover, we studied determinants of QTc
      prolongation at SR(postAF). We found that, in all groups, QTc at SR(postAF) was
      significantly and transiently prolonged compared with SR(baseline). Although of
      limited magnitude on average (approximately 5%), the increase was substantial
      (approximately 15%) in some individuals. The only independent predictor of the
      magnitude of QTc prolongation was QTc duration at SR(baseline); this relation had
      a negative correlation. CONCLUSION: AF causes ventricular repolarization
      remodelling, resulting in QTc prolongation. QTc prolongation is substantial in
      some patients and may render these patients vulnerable to pro-arrhythmia from
      class IA/III antiarrhythmic drugs immediately after termination of AF.

PMID- 18094019
TI  - Demographic, structural and genetic predictors of late cognitive decline after
      penetrating head injury.
AB  - We examined the relationship of pre-injury intelligence, demographic variables,
      lesion location, brain tissue volume loss and a number of genetic markers to long
      term cognitive decline in a group of Vietnam veterans with predominantly
      penetrating head injury (PHI) suffered more than 30 years ago. Using linear and
      stepwise regression procedures, we found that those with PHI demonstrated a
      greater degree of cognitive decline overall during the years following recovery
      from injury compared with a control group of uninjured Vietnam veterans. This
      became increasingly significant later in life. We also found that pre-injury
      intelligence was the most consistent predictor of cognitive outcome across all
      phases of potential recovery and decline after such injuries. While laterality of
      lesion was not a factor, we did find some associations between atrophy and
      specific regions of tissue loss and long-term cognitive functioning. Finally, we
      found evidence for an association between level of cognitive decline following
      PHI and the possession of certain genetic markers that have been linked with
      brain injury and neurodegeneration. Thus exacerbated decline does occur in
      Vietnam veterans with PHI and it is apparently unrelated to dementia and is
      determined by multiple factors (most notably pre-injury intelligence).

PMID- 18094020
TI  - Abnormal activity in hypothalamus and amygdala during humour processing in human
      narcolepsy with cataplexy.
AB  - Narcolepsy with cataplexy (NC) is a complex sleep-wake disorder, which was
      recently found to be associated with a reduction or loss of hypocretin (HCRT,
      also called orexin). HCRT is a hypothalamic peptide implicated in the regulation
      of sleep/wake, motor and feeding functions. Cataplexy refers to episodes of
      sudden and transient loss of muscle tone triggered by strong, mostly positive
      emotions, such as hearing or telling jokes. Cataplexy is thought to reflect the
      recruitment of ponto-medullary mechanisms that normally underlie muscle atonia
      during REM-sleep. In contrast, the suprapontine brain mechanisms associated with
      the cataplectic effects of emotions in human narcolepsy with cataplexy remain
      essentially unknown. Here, we used event-related functional MRI to assess brain
      activity in 12 NC patients and 12 controls while they watched sequences of
      humourous pictures. Patients and controls were similar in humour appreciation and
      activated regions known to contribute to humour processing, including limbic and
      striatal regions. A direct statistical comparison between patients and controls
      revealed that humourous pictures elicited reduced hypothalamic response together
      with enhanced amygdala response in the patients. These results suggest (i) that
      hypothalamic HCRT activity physiologically modulates the processing of emotional
      inputs within the amygdala, and (ii) that suprapontine mechanisms of cataplexy
      involve a dysfunction of hypothalamic-amygdala interactions triggered by positive
      emotions.

PMID- 18094021
TI  - Lgl and its phosphorylation by aPKC regulate oocyte polarity formation in
      Drosophila.
AB  - Specification of the anteroposterior (AP) axis in Drosophila oocytes requires
      proper organization of the microtubule and actin cytoskeleton. The establishment
      and regulation of cytoskeletal polarity remain poorly understood, however. Here,
      we show important roles for the tumor suppressor Lethal (2) giant larvae (Lgl)
      and atypical protein kinase C (aPKC) in regulating microtubule polarity and
      setting up the AP axis of the oocyte. Lgl in the germline cells regulates the
      localization of axis-specifying morphogens. aPKC phosphorylation of Lgl restricts
      Lgl activity to the oocyte posterior, thereby dividing the cortex into different
      domains along the AP axis. Active Lgl promotes the formation of actin-rich
      projections at the oocyte cortex and the posterior enrichment of the
      serine/threonine kinase Par-1, a key step for oocyte polarization. Our studies
      suggest that Lgl and its phosphorylation by aPKC may form a conserved regulatory
      circuitry in polarization of various cell types.

PMID- 18094022
TI  - Free-radical crosslinking of specific proteins alters the function of the egg
      extracellular matrix at fertilization.
AB  - All animal embryos begin development by modifying the egg extracellular matrix.
      This protein-rich matrix protects against polyspermy, microbes and mechanical
      stress via enzyme-dependent transformations that alter the organization of its
      constituents. Using the sea urchin fertilization envelope, a well-defined
      extracellular structure formed within minutes of fertilization, we examine the
      mechanisms whereby limited permeability is established within this matrix. We
      find that the fertilization envelope acquires a barrier filtration of 40,000
      daltons within minutes of insemination via a peroxidase-dependent mechanism, with
      dynamics that parallel requisite production of hydrogen peroxide by the zygote.
      To identify the molecular targets of this free-radical modification, we developed
      an in vivo technique to label and isolate the modified matrix components for mass
      spectrometry. This method revealed that four of the six major extracellular
      matrix components are selectively crosslinked, discriminating even sibling
      proteins from the same gene. Thus, specific free-radical chemistry is essential
      for establishing the embryonic microenvironment of early development.

PMID- 18094023
TI  - Constitutive PtdIns(3,4,5)P3 synthesis promotes the development and survival of
      early mammalian embryos.
AB  - Mammalian preimplantation embryos develop in the oviduct as individual entities,
      and can develop and survive in vitro, in defined culture media lacking exogenous
      growth factors or serum. Therefore, early embryos must generate intrinsic signals
      that promote their development and survival. In other cells, activation of class
      I phosphoinositide 3-kinase (PI3K) is a universal mechanism to promote cell
      proliferation and survival. Here, we examined whether PI3K is intrinsically
      activated during preimplantation development. Using GFP-tagged pleckstrin
      homology domains to monitor PtdIns(3,4,5)P(3) synthesis, we show that PI3K is
      constitutively activated in mouse preimplantation embryos. E-cadherin ligation
      promotes PtdIns(3,4,5)P(3) synthesis at sites of blastomere adhesion at all
      cleavage stages. In addition, in culture conditions that promote autocrine
      signalling, a second pool of PtdIns(3,4,5)P(3) is generated in the apical
      membrane of early stage blastomeres. We show that constitutive PtdIns(3,4,5)P(3)
      synthesis is necessary for optimal development to blastocyst and to prevent large
      scale apoptosis at the time of cavitation.

PMID- 18094024
TI  - FGF signaling regulates mesenchymal differentiation and skeletal patterning along
      the limb bud proximodistal axis.
AB  - Fibroblast growth factors (FGFs) are signals from the apical ectodermal ridge
      (AER) that are essential for limb pattern formation along the proximodistal (PD)
      axis. However, how patterning along the PD axis is regulated by AER-FGF signals
      remains controversial. To further explore the molecular mechanism of FGF
      functions during limb development, we conditionally inactivated fgf receptor 2
      (Fgfr2) in the mouse AER to terminate all AER functions; for comparison, we
      inactivated both Fgfr1 and Fgfr2 in limb mesenchyme to block mesenchymal AER-FGF
      signaling. We also re-examined published data in which Fgf4 and Fgf8 were
      inactivated in the AER. We conclude that limb skeletal phenotypes resulting from
      loss of AER-FGF signals cannot simply be a consequence of excessive mesenchymal
      cell death, as suggested by previous studies, but also must be a consequence of
      reduced mesenchymal proliferation and a failure of mesenchymal differentiation,
      which occur following loss of both Fgf4 and Fgf8. We further conclude that
      chondrogenic primordia formation, marked by initial Sox9 expression in limb
      mesenchyme, is an essential component of the PD patterning process and that a key
      role for AER-FGF signaling is to facilitate SOX9 function and to ensure
      progressive establishment of chondrogenic primordia along the PD axis.

PMID- 18094025
TI  - Insm1 (IA-1) is a crucial component of the transcriptional network that controls
      differentiation of the sympatho-adrenal lineage.
AB  - Insm1 (IA-1) encodes a Zn-finger factor that is expressed in the developing
      nervous system. We demonstrate here that the development of the sympatho-adrenal
      lineage is severely impaired in Insm1 mutant mice. Differentiation of sympatho
      adrenal precursors, as assessed by the expression of neuronal subtype-specific
      genes such as Th and Dbh, is delayed in a pronounced manner, which is accompanied
      by a reduced proliferation. Sympathetic neurons eventually overcome the
      differentiation blockade and mature correctly, but sympathetic ganglia remain
      small. By contrast, terminal differentiation of adrenal chromaffin cells does not
      occur. The transcription factors Mash1 (Ascl1), Phox2a, Gata3 and Hand2
      (previously dHand) control the differentiation of sympatho-adrenal precursor
      cells, and their deregulated expression in Insm1 mutant mice demonstrates that
      Insm1 acts in the transcriptional network that controls differentiation of this
      lineage. Pronounced similarities between Mash1 and Insm1 phenotypes are apparent,
      which suggests that Insm1 might mediate aspects of Mash1 function in the subtype
      specific differentiation of sympatho-adrenal precursors. Noradrenaline is the
      major catecholamine produced by developing sympatho-adrenal cells and is required
      for fetal survival. We demonstrate that the fetal lethality of Insm1 mutant mice
      is caused by catecholamine deficiency, which highlights the importance of Insm1
      in the development of the sympatho-adrenal lineage.

PMID- 18094026
TI  - The chromatin-remodeling enzyme BRG1 plays an essential role in primitive
      erythropoiesis and vascular development.
AB  - ATP-dependent chromatin-remodeling complexes contribute to the proper temporal
      and spatial patterns of gene expression in mammalian embryos and therefore play
      important roles in a number of developmental processes. SWI/SNF-like chromatin
      remodeling complexes use one of two different ATPases as their catalytic subunit:
      brahma (BRM, also known as SMARCA2) and brahma-related gene 1 (BRG1, also known
      as SMARCA4). We have conditionally deleted a floxed Brg1 allele with a Tie2-Cre
      transgene, which is expressed in developing hematopoietic and endothelial cells.
      Brg1(fl/fl):Tie2-Cre(+) embryos die at midgestation from anemia, as mutant
      primitive erythrocytes fail to transcribe embryonic alpha- and beta-globins, and
      subsequently undergo apoptosis. Additionally, vascular remodeling of the
      extraembryonic yolk sac is abnormal in Brg1(fl/fl):Tie2-Cre(+) embryos.
      Importantly, Brm deficiency does not exacerbate the erythropoietic or vascular
      abnormalities found in Brg1(fl/fl):Tie2-Cre(+) embryos, implying that Brg1
      containing SWI/SNF-like complexes, rather than Brm-containing complexes, play a
      crucial role in primitive erythropoiesis and in early vascular development.

PMID- 18094027
TI  - Six3 inactivation causes progressive caudalization and aberrant patterning of the
      mammalian diencephalon.
AB  - The homeobox gene Six3 represses Wnt1 transcription. It is also required in the
      anterior neural plate for the development of the mammalian rostral forebrain. We
      have now determined that at the 15- to 17-somite stage, the prospective
      diencephalon is the most-anterior structure in the Six3-null brain, and Wnt1
      expression is anteriorly expanded. Consequently, the brain caudalizes, and at the
      22- to 24-somite stage, the prospective thalamic territory is the most-anterior
      structure. At around E11.0, the pretectum replaces this structure. Analysis of
      Six3;Wnt1 double-null mice revealed that Six3-mediated repression of Wnt1 is
      necessary for the formation of the rostral diencephalon and that Six3 activity is
      required for the formation of the telencephalon. These results provide insight
      into the mechanisms that establish anteroposterior identity in the developing
      mammalian brain.

PMID- 18094028
TI  - The Gata5 target, TGIF2, defines the pancreatic region by modulating BMP signals
      within the endoderm.
AB  - Mechanisms underlying regional specification of distinct organ precursors within
      the endoderm, including the liver and pancreas, are still poorly understood. This
      is particularly true for stages between endoderm formation and the initiation of
      organogenesis. In this report, we have investigated these intermediate steps
      downstream of the early endodermal factor Gata5, which progressively lead to the
      induction of pancreatic fate. We have identified TGIF2 as a novel Gata5 target
      and demonstrate its function in the establishment of the pancreatic region within
      dorsal endoderm in Xenopus. TGIF2 acts primarily by restricting BMP signaling in
      the endoderm to allow pancreatic formation. Consistently, we found that blocking
      BMP signaling by independent means also perturbs the establishment of pancreatic
      identity in the endoderm. Previous findings demonstrated a crucial role for BMP
      signaling in determining dorsal/ventral fates in ectoderm and mesoderm. Our
      results now extend this trend to the endoderm and identify TGIF2 as the molecular
      link between dorsoventral patterning of the endoderm and pancreatic
      specification.

PMID- 18094029
TI  - Eplerenone potentiates the antiproteinuric effects of enalapril in experimental
      nephrotic syndrome.
AB  - Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria
      and edema. It is believed that nephrin and podocin are involved in the
      development of proteinuria. The proteinuria and effects of eplerenone alone or
      combined with enalapril on nephrin/podocin abundance in rats with NS have not yet
      been studied. Therefore, the present study was designed to examine the early
      (beginning 2 days before NS induction) and late (beginning 2 wk after NS
      induction) effects of eplerenone and enalapril, alone or combined, on proteinuria
      and nephrin/podocin abundance in rats with adriamycin-induced NS. Adriamycin
      caused a significant increase in daily protein excretion (U(pr)V; from 26.96 +/-
      3.43 to 958.57 +/- 56.7 mg/day, P < 0.001) and cumulative proteinuria [from
      900.33 +/- 135.5 to 22,490.62 +/- 931.26 mg (P < 0.001)] during 6 wk. Early
      treatment with enalapril significantly decreased U(pr)V from 958.6 +/- 56.7 to
      600.31 +/- 65.13 mg/day (P < 0.001) and cumulative proteinuria to 12,842.37 +/-
      1,798.17 mg/6 wk (P < 0.001). Similarly, early treatment with eplerenone produced
      a profound antiproteinuric effect: U(pr)V decreased from 958.57 +/- 56.7 to
      593.38 +/- 21.83 mg/day, P < 0.001, and cumulative proteinuria to 16,601.84 +/-
      1,334.31 mg/6 wk; P < 0.001. An additive effect was obtained when enalapril and
      eplerenone were combined: U(pr)V decreased from 958.57 +/- 56.69 to 424.17 +/-
      38.54 mg/day, P < 0.001, and cumulative protein excretion declined to 10,252.88
      +/- 1,011.3 mg/6 wk, P < 0.001. These antiproteinuric effects were associated
      with substantial preservation of glomerular nephrin and podocin. In contrast,
      late treatment with either enalapril or eplerenone alone or combined mildly
      decreased U(pr)V and cumulative proteinuria. Thus pretreatment with eplerenone or
      enalapril is effective in reducing daily and cumulative protein excretion and
      preservation of nephrin/podocin. More profound antiproteinuric effects were
      obtained when enalapril and eplerenone were combined.

PMID- 18094030
TI  - Restoration of CREB function ameliorates cisplatin cytotoxicity in renal tubular
      cells.
AB  - We have shown that mouse proximal tubule cells (TKPTS) survive H(2)O(2) stress by
      activating the cAMP-responsive element binding protein (CREB)-mediated
      transcription via the canonical EGFR-Ras/ERK pathway. By contrast, cisplatin
      activates EGFR/Ras/ERK signaling in TKPTS cells yet promotes cell death rather
      than survival. We now demonstrate that the cisplatin-induced activated
      EGFR/Ras/ERK signaling cascade fails to activate CREB-mediated transcription even
      in the presence of phosphorylated CREB. CREB-mediated transcription as well as
      survival was restored by the histone deacetylase (HDAC) inhibitor trichostatine A
      (TSA), an effective chemotherapeutic agent. Similar to severe oxidant stress, TSA
      mediated survival could be abrogated by inhibition of CREB-mediated
      transcription. These studies confirm the importance of CREB-mediated
      transcription in the survival of renal cells subjected to either oxidant- or
      cisplatin-induced stress. The use of cisplatin and TSA in combined chemotherapy
      protocols may be an effective strategy to enhance cancer cell death and limit
      nephrotoxicity.

PMID- 18094031
TI  - Role of AQP2 in activation of calcium entry by hypotonicity: implications in cell
      volume regulation.
AB  - We previously reported in a rat cortical collecting duct cell line (RCCD(1)) that
      the presence of aquaporin 2 (AQP2) in the cell membrane is critical for the rapid
      activation of regulatory volume decrease mechanisms (RVD) (Ford et al. Biol Cell
      97: 687-697, 2005). The aim of our present work was to investigate the signaling
      pathway that links AQP2 to this rapid RVD activation. Since it has been
      previously described that hypotonic conditions induce intracellular calcium
      ([Ca(2+)](i)) increases in different cell types, we tested the hypothesis that
      AQP2 could have a role in activation of calcium entry by hypotonicity and its
      implication in cell volume regulation. Using a fluorescent probe technique, we
      studied [Ca(2+)](i) and cell volume changes in response to a hypotonic shock in
      WT-RCCD(1) (not expressing aquaporins) and in AQP2-RCCD(1) (transfected with
      AQP2) cells. We found that after a hypotonic shock only AQP2-RCCD(1) cells
      exhibit a substantial increase in [Ca(2+)](i). This [Ca(2+)](i) increase is
      strongly dependent on extracellular Ca(2+) and is partially inhibited by
      thapsigargin (1 muM) indicating that the rise in [Ca(2+)](i) reflects both influx
      from the extracellular medium and release from intracellular stores. Exposure of
      AQP2-RCCD(1) cells to 100 muM gadolinium reduced the increase in [Ca(2+)](i)
      suggesting the involvement of a mechanosensitive calcium channel. Furthermore,
      exposure of cells to all of the above described conditions impaired rapid RVD. We
      conclude that the expression of AQP2 in the cell membrane is critical to produce
      the increase in [Ca(2+)](i) which is necessary to activate RVD in RCCD(1) cells.

PMID- 18094032
TI  - Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced
      chronic glomerulosclerosis of the rat.
AB  - Treatment options in human mesangioproliferative glomerulonephritis/sclerosis,
      mostly IgA nephropathy, are limited. Progressive mesangioproliferative
      nephropathy represents a major cause of end-stage kidney disease. The present
      study explores the efficacy of low-dose mTOR inhibition by rapamycin in a chronic
      progressive model of mesangioproliferative glomerulosclerosis (cGS). cGS was
      induced by high-dose anti-thy1 antibody injection into uninephrectomized rats.
      Rapamycin administration (2.5 mg.kg(-1).body wt(-1)) was started 10 days after
      antibody injection and continued until week 20. cGS was characterized by
      advancing proteinuria, increased blood pressure, marked tubulointerstitial and
      glomerular fibrosis, cell proliferation and round cell infiltration, and impaired
      renal function. Kruskal-Wallis and Mann-Whitney U-tests were used for statistical
      analysis. The course of chronic anti-thy1-induced glomerulosclerosis was
      significantly attenuated by low-dose rapamycin treatment. In week 20, this was
      demonstrated by improvements in proteinuria (-38%), systolic blood pressure (-16
      mmHg), tubulointerstitial and glomerular histological matrix accumulation (-61
      and -24%), transforming growth factor-beta1 overexpression (-41 and -47%),
      collagen I deposition (-53 and -65%), cell proliferation (-90 and -76%), and
      leukocyte number (macrophages -52 and -53%; lymphocytes -58 and 51%),
      respectively. Rapamycin improved renal function as well (blood creatinine -0.68
      mg/dl, urea -66.7 mg/day, and creatinine clearance +0.13 ml.min(-1).100 g body
      wt(-1)). In conclusion, low-dose mTOR inhibition by rapamycin limits the
      progressive course of anti-thy1-induced renal disease toward chronic
      glomerulosclerosis, tubulointerstitial fibrosis, and renal insufficiency.
      Renoprotection by rapamycin involved significant beneficial effects on multiple
      key pathways in the progression of chronic renal disease, i.e., proteinuria,
      extracellular matrix accumulation, renal cell proliferation, and inflammatory
      cell infiltration.

PMID- 18094033
TI  - Upregulation of cortical COX-2 in salt-sensitive hypertension: role of
      angiotensin II and reactive oxygen species.
AB  - Salt-sensitive (SS) hypertension is a vascular diathesis characterized by reduced
      cardiovascular and renal nitric oxide bioavailability and local upregulation of
      ANG II. We have demonstrated that rats infused with ANG II manifest increased
      cortical cyclooxygenase (COX)-2 expression and activity via NADPH oxidase-derived
      reactive oxygen species (ROS). In the present studies we used Dahl salt-sensitive
      (DS) rats to test the hypothesis that hypertensive SS rats have increased
      cortical COX-2 upregulation, which is mediated by ANG II and ROS. DS rats were
      placed on either a normal-salt diet (0.5% NaCl) or a high-salt diet (4% NaCl) for
      6 wk and treated with either the ANG II type 1 (AT1) receptor blocker candesartan
      (Can, 10 mg.kg(-1).day(-1)) or the SOD mimetic tempol (1 mmol/l). Hypertensive SS
      rats had a twofold increase in the cortical expression of COX-2 as assessed by
      Western blot. These changes in COX-2 expression were accompanied by a 10-fold
      increase in COX-2 mRNA expression and a 2-fold increase in the urinary excretion
      of PGE2. Treatment with either the AT1 receptor blocker Can or the SOD mimetic
      tempol did not reduce blood pressure but resulted in significant reductions in
      the cortical expression of COX-2 and the urinary excretion of PGE2. In
      conclusion, we have demonstrated that local activation of the renin-angiotensin
      system, via increased ROS generation, mediates COX-2 upregulation in hypertensive
      SS rats. These studies unveil novel mechanistic pathways that may play a role in
      the pathogenesis of hypertensive renal injury.

PMID- 18094034
TI  - Isoform specificity of Na-K-ATPase-mediated ouabain signaling.
AB  - The ion transporter Na-K-ATPase functions as a cell signal transducer that
      mediates ouabain-induced activation of protein kinases, such as ERK. While Na-K
      ATPase composed of the alpha(1)-polypeptide is involved in cell signaling, the
      role of other alpha-isoforms (alpha(2), alpha(3), and alpha(4)) in transmitting
      ouabain effects is unknown. We have explored this using baculovirus-directed
      expression of Na-K-ATPase polypeptides in insect cells and ERK phosphorylation as
      an indicator of ouabain-induced signaling. Ouabain addition to Sf-9 cells
      coexpressing Na-K-ATPase alpha(1)- and beta(1)-isoforms stimulated ERK
      phosphorylation. In contrast, expression of the alpha(1)- and beta(1)
      polypeptides alone resulted in no effect, indicating that the alphabeta-complex
      is necessary for Na-K-ATPase signaling. Moreover, the ouabain effect was
      sensitive to genistein, suggesting that Na-K-ATPase-mediated tyrosine kinase
      activation is a critical event in the intracellular cascade leading to ERK
      phosphorylation. In addition, the Na-K-ATPases alpha(3)beta(1)- and
      alpha(4)beta(1)-isozymes, but not alpha(2)beta(1), responded to ouabain
      treatment. In agreement with the differences in ouabain affinity of the alpha
      polypeptides, alpha(1)beta(1) required 100- to 1,000-fold more ouabain to signal
      than did alpha(4)beta(1) and alpha(3)beta(1), respectively. These results confirm
      the role of the Na-K-ATPase in ouabain signal transduction, show that there are
      important isoform-specific differences in Na-K-ATPase signaling, and demonstrate
      the suitability of the baculovirus expression system for studying Na-K-ATPase
      mediated ouabain effects.

PMID- 18094037
TI  - Induction of metabolism and transport in human intestine: validation of precision
      cut slices as a tool to study induction of drug metabolism in human intestine in
      vitro.
AB  - Induction of drug enzyme activity in the intestine can strongly determine plasma
      levels of drugs. It is therefore important to predict drug-drug interactions in
      human intestine in vitro. We evaluated the applicability of human intestinal
      precision-cut slices for induction studies in vitro. Morphological examination
      and intracellular ATP levels indicated tissue integrity up to 24 h of incubation,
      whereas in proximal jejunum slices, the metabolic rate toward most substrates
      remained at 40 to 50% of initial values. In colon slices, the cytochrome P450
      conversions were below the detection limit, but conjugation rates remained
      relatively constant during incubation. The inducibility of drug-metabolizing
      enzymes and P-glycoprotein was evaluated using prototypical inducers for five
      induction pathways. beta-Naphthoflavone (aryl hydrocarbon receptor ligand)
      induced CYP1A1 (132-fold in colon and 362-fold in proximal jejunum) and UDP
      glucuronosyltransferase (UGT) 1A6 mRNA (9.8-fold in colon and 3.2-fold in
      proximal jejunum). In proximal jejunum, rifampicin (RIF) [pregnane X receptor
      (PXR) ligand] induced CYP3A4 (5.2-fold), CYP2B6 (2-fold), UGT1A6 (2.2-fold), and
      multidrug resistance-1 (MDR1)/ABCB1 mRNA (2.7-fold), whereas 6beta
      hydroxytestosterone formation (CYP3A4) increased 2-fold. In colon, RIF induced
      UGT1A6 32-fold and MDR1 2.2-fold. Dexamethasone (glucocorticoid receptor and PXR
      ligand) induced CYP3A4 mRNA (3.5-fold) and activity (5-fold) in proximal jejunum.
      Phenobarbital (constitutive androstane receptor activator) induced CYP3A4 (4.1
      fold, only in jejunum), CYP2B6 (4.9-fold in colon and 2.3-fold in proximal
      jejunum), and MDR1/ABCB1 mRNA and CYP3A4 activity (2-fold only proximal jejunum).
      Quercetin (nuclear factor-E2-related factor 2 activator) induced UGT1A6 mRNA (6.7
      fold in colon and 2.2-fold in proximal jejunum). In conclusion, this study shows
      that human intestinal precision-cut slices are useful to study induction of drug
      metabolizing enzymes and transporters in the human intestine.

PMID- 18094035
TI  - Protective effects of low-dose carbon monoxide against renal fibrosis induced by
      unilateral ureteral obstruction.
AB  - Tubulointerstitial fibrosis is a hallmark of chronic progressive kidney disease
      leading to end-stage renal failure. An endogenous product of heme oxygenase
      activity, carbon monoxide (CO), has been shown to exert cytoprotection against
      tissue injury. Here, we explored the effects of exogenous administration of low
      dose CO in an in vivo model of renal fibrosis induced by unilateral ureteral
      obstruction (UUO) and examined whether CO can protect against kidney injury. UUO
      in mice leads to increased extracellular matrix (ECM) deposition and
      tubulointerstitial fibrosis within 4 to 7 days. Kidneys of mice exposed to low
      dose CO, however, had markedly reduced ECM deposition after UUO. Moreover, low
      dose CO treatment inhibited the induction of alpha-smooth muscle actin (alpha
      SMA) and major ECM proteins, type 1 collagen and fibronectin, in kidneys after
      UUO. In contrast, these anti-fibrotic effects of CO treatment were abrogated in
      mice carrying null mutation of Mkk3, suggesting involvement of the MKK3 signaling
      pathway in mediating the CO effects. Additionally, in vitro CO exposure markedly
      inhibited TGF-beta(1)-induced expression of alpha-SMA, collagen, and fibronectin
      in renal proximal tubular epithelial cells. Our findings suggest that low-dose CO
      exerts protective effects, via the MKK3 pathway, to inhibit development of renal
      fibrosis in obstructive nephropathy.

PMID- 18094038
TI  - High-affinity binding of [3H]cimetidine to a heme-containing protein in rat
      brain.
AB  - [(3)H]Cimetidine (3HCIM) specifically binds to an unidentified site in the rat
      brain. Because recently described ligands for this site have pharmacological
      activity, 3HCIM binding was characterized. 3HCIM binding was saturable, heat
      labile, and distinct from the histamine H(2) receptor. To test the hypothesis
      that 3HCIM binds to a cytochrome P450 (P450), the effects of nonselective and
      isoform-selective P450 inhibitors were studied. The heme inhibitor KCN and the
      nonselective P450 inhibitor metyrapone both produced complete, concentration
      dependent inhibition of 3HCIM binding (K(i) = 1.3 mM and 11.9 muM, respectively).
      Binding was largely unaffected by inhibitors of CYP1A2, 2B6, 2C8, 2C9, 2D6, 2E1,
      and 19A1 but was eliminated by inhibitors of CYP2C19 (tranylcypromine) and CYP3A4
      (ketoconazole). Synthesis and testing of CC11 [4(5)-(benzylthiomethyl)-1H
      imidazole] and CC12 [4(5)-((4-iodobenzyl)-thiomethyl)-1H-imidazole] confirmed
      both drugs to be high-affinity inhibitors of 3HCIM binding. On recombinant human
      P450s, CC12 was a potent inhibitor of CYP2B6 (IC(50) = 11.7 nM), CYP2C19 (51.4
      nM), and CYP19A1 (140.7 nM) and had a range of activities (100-494 nM) on nine
      other isoforms. Although the 3HCIM binding site pharmacologically resembles some
      P450s, eight recombinant human P450s and three recombinant rat P450s did not
      exhibit 3HCIM binding. Inhibition by KCN and metyrapone suggests that 3HCIM binds
      to a heme-containing brain protein (possibly a P450). However, results with
      selective P450 inhibitors, recombinant P450 isoforms, and a P450 antibody did not
      identify a 3HCIM-binding P450 isoform. Finally, CC12 is a new, potent inhibitor
      of CYP2B6 and CYP2C19 that may be a valuable tool for P450 research.

PMID- 18094039
TI  - Induction of autophagy during extracellular matrix detachment promotes cell
      survival.
AB  - Autophagy has been proposed to promote cell death during lumen formation in three
      dimensional mammary epithelial acini because numerous autophagic vacuoles are
      observed in the dying central cells during morphogenesis. Because these central
      cells die due to extracellular matrix (ECM) deprivation (anoikis), we have
      directly interrogated how matrix detachment regulates autophagy. Detachment
      induces autophagy in both nontumorigenic epithelial lines and in primary
      epithelial cells. RNA interference-mediated depletion of autophagy regulators
      (ATGs) inhibits detachment-induced autophagy, enhances apoptosis, and reduces
      clonogenic recovery after anoikis. Remarkably, matrix-detached cells still
      exhibit autophagy when apoptosis is blocked by Bcl-2 overexpression, and ATG
      depletion reduces the clonogenic survival of Bcl-2-expressing cells after
      detachment. Finally, stable reduction of ATG5 or ATG7 in MCF-10A acini enhances
      luminal apoptosis during morphogenesis and fails to elicit long-term luminal
      filling, even when combined with apoptotic inhibition mediated by Bcl-2
      overexpression. Thus, autophagy promotes epithelial cell survival during anoikis,
      including detached cells harboring antiapoptotic lesions.

PMID- 18094040
TI  - Dysferlin domain-containing proteins, Pex30p and Pex31p, localized to two
      compartments, control the number and size of oleate-induced peroxisomes in Pichia
      pastoris.
AB  - Yarrowia lipolytica Pex23p and Saccharomyces cerevisiae Pex30p, Pex31p, and
      Pex32p comprise a family of dysferlin domain-containing peroxins. We show that
      the deletion of their Pichia pastoris homologues, PEX30 and PEX31, does not
      affect the function or division of methanol-induced peroxisomes but results in
      fewer and enlarged, functional, oleate-induced peroxisomes. Synthesis of Pex30p
      is constitutive, whereas that of Pex31p is oleate-induced but at a much lower
      level relative to Pex30p. Pex30p interacts with Pex31p and is required for its
      stability. At steady state, both Pex30p and Pex31p exhibit a dual localization to
      the endoplasmic reticulum (ER) and peroxisomes. However, Pex30p is localized
      mostly to the ER, whereas Pex31p is predominantly on peroxisomes. Consistent with
      ER-to-peroxisome trafficking of these proteins, Pex30p accumulates on peroxisomes
      upon overexpression of Pex31p. Additionally, Pex31p colocalizes with Pex30p at
      the ER in pex19Delta cells and can be chased from the ER to peroxisomes in a
      Pex19p-dependent manner. The dysferlin domains of Pex30p and Pex31p, which are
      dispensable for their interaction, stability, and subcellular localization, are
      essential for normal peroxisome number and size. The growth environment-specific
      role of these peroxins, their dual localization, and the function of their
      dysferlin domains provide novel insights into peroxisome morphogenesis.

PMID- 18094041
TI  - Transforming growth factor beta controls the directional migration of hepatocyte
      cohorts by modulating their adhesion to fibronectin.
AB  - Transforming growth factor beta (TGF-beta) has a strong impact on liver
      development and physiopathology, exercised through its pleiotropic effects on
      growth, differentiation, survival, and migration. When exposed to TGF-beta, the
      mhAT3F cells, immortalized, highly differentiated hepatocytes, maintained their
      epithelial morphology and underwent dramatic alterations of adhesion, leading to
      partial or complete detachment from a culture plate, followed by readhesion and
      spreading. These alterations of adhesive behavior were caused by sequential
      changes in expression of the alpha5beta1 integrin and of its ligand, the
      fibronectin. The altered specificity of anchorage to the extracellular matrix
      gave rise to changes in cells' collective motility: cohorts adhering to
      fibronectin maintained a persistent, directional motility, with ezrin-rich
      pathfinder cells protruding from the tips of the cohorts. The absence of adhesion
      to fibronectin prevented the appearance of polarized pathfinders and lead to
      random, oscillatory motility. Our data suggest a novel role for TGF-beta in the
      control of collective migration of epithelial cohorts.

PMID- 18094042
TI  - Caenorhabditis elegans mboa-7, a member of the MBOAT family, is required for
      selective incorporation of polyunsaturated fatty acids into phosphatidylinositol.
AB  - Phosphatidylinositol (PI) is a component of membrane phospholipids, and it
      functions both as a signaling molecule and as a compartment-specific localization
      signal in the form of polyphosphoinositides. Arachidonic acid (AA) is the
      predominant fatty acid in the sn-2 position of PI in mammals. LysoPI
      acyltransferase (LPIAT) is thought to catalyze formation of AA-containing PI;
      however, the gene that encodes this enzyme has not yet been identified. In this
      study, we established a screening system to identify genes required for use of
      exogenous polyunsaturated fatty acids (PUFAs) in Caenorhabditis elegans. In C.
      elegans, eicosapentaenoic acid (EPA) instead of AA is the predominant fatty acid
      in PI. We showed that an uncharacterized gene, which we named mboa-7, is required
      for incorporation of PUFAs into PI. Incorporation of exogenous PUFA into PI of
      the living worms and LPIAT activity in the microsomes were greatly reduced in
      mboa-7 mutants. Furthermore, the membrane fractions of transgenic worms
      expressing recombinant MBOA-7 and its human homologue exhibited remarkably
      increased LPIAT activity. mboa-7 encodes a member of the membrane-bound O
      acyltransferase family, suggesting that mboa-7 is LPIAT. Finally, mboa-7 mutants
      had significantly lower EPA levels in PI, and they exhibited larval arrest and
      egg-laying defects.

PMID- 18094043
TI  - Coordinated vascular endothelial growth factor expression and signaling during
      skeletal myogenic differentiation.
AB  - Angiogenesis is largely controlled by hypoxia-driven transcriptional up
      regulation and secretion of vascular endothelial growth factor (VEGF) and its
      binding to the endothelial cell tyrosine receptor kinases, VEGFR1 and VEGFR2.
      Recent expression analysis suggests that VEGF is expressed in a cell-specific
      manner in normoxic adult tissue; however, the transcriptional regulation and role
      of VEGF in these tissues remains fundamentally unknown. In this report we
      demonstrate that VEGF is coordinately up-regulated during terminal skeletal
      muscle differentiation. We reveal that this regulation is mediated in part by
      MyoD homo- and hetero-dimeric transcriptional mechanisms. Serial deletions of the
      VEGF promoter elucidated a region containing three tandem CANNTG consensus MyoD
      sites serving as essential sites of direct interaction for MyoD-mediated up
      regulation of VEGF transcription. VEGF-null embryonic stem (ES) cells exhibited
      reduced myogenic differentiation compared with wild-type ES cells, suggesting
      that VEGF may serve a role in skeletal muscle differentiation. We demonstrate
      that VEGFR1 and VEGFR2 are expressed at low levels in myogenic precursor cells
      and are robustly activated upon VEGF stimulation and that their expression is
      coordinately regulated during skeletal muscle differentiation. VEGF stimulation
      of differentiating C2C12 cells promoted myotube hypertrophy and increased
      myogenic differentiation, whereas addition of sFlt1, a VEGF inhibitor, resulted
      in myotube hypotrophy and inhibited myogenic differentiation. We further provide
      evidence indicating VEGF-mediated myogenic marker expression, mitogenic activity,
      migration, and prosurvival functions may contribute to increased myogenesis.
      These data suggest a novel mechanism whereby VEGF is coordinately regulated as
      part of the myogenic differentiation program and serves an autocrine function
      regulating skeletal myogenesis.

PMID- 18094044
TI  - A unique platform for H-Ras signaling involving clathrin-independent endocytosis.
AB  - Trafficking of H-Ras was examined to determine whether it can enter cells through
      clathrin-independent endocytosis (CIE). H-Ras colocalized with the CIE cargo
      protein, class I major histocompatibility complex, and it was sequestered in
      vacuoles that formed upon expression of an active mutant of Arf6, Q67L.
      Activation of Ras, either through epidermal growth factor stimulation or the
      expression of an active mutant of Ras, G12V, induced plasma membrane ruffling and
      macropinocytosis, a stimulated form of CIE. Live imaging of cells expressing H
      RasG12V and fluorescent protein chimeras with pleckstrin homology domains that
      recognize specific phosphoinositides showed that incoming macropinosomes
      contained phosphatidylinositol 4,5-bisphosphate (PIP(2)) and phosphatiylinositol
      3,4,5-trisphosphate (PIP(3)). PIP(2) loss from the macropinosome was followed by
      the recruitment of Rab5, a downstream target of Ras, and then PIP(3) loss. Our
      studies support a model whereby Ras can signal on macropinosomes that pass
      through three distinct stages: PIP(2)/PIP(3), PIP(3)/Rab5, and Rab5. Vacuoles
      that form in cells expressing Arf6Q67L trap Ras signaling in the first stage,
      recruiting the active form of the Ras effectors extracellular signal-regulated
      kinase and protein kinase B (Akt) but not Rab5. Arf6 stimulation of
      macropinocytosis also involves passage through the distinct lipid phases, but
      recruitment of Akt is not observed.

PMID- 18094045
TI  - Fbx8 makes Arf6 refractory to function via ubiquitination.
AB  - The small GTP-binding protein Arf6 regulates membrane remodeling at cell
      peripheries and plays crucial roles in higher orders of cellular functions
      including tumor invasion. Here we show that Fbx8, an F-box protein bearing the
      Sec7 domain, mediates ubiquitination of Arf6. This ubiquitination did not appear
      to be linked to immediate proteasomal degradation of Arf6, whereas Fbx8 knockdown
      caused hyperactivation of Arf6. Expression of Fbx8 protein was substantially lost
      in several breast tumor cell lines, in which Arf6 activity is pivotal for their
      invasion. Forced expression of Fbx8 in these cells suppressed their Arf6
      activities and invasive activities, in which the F-box and Sec7 domains of Fbx8
      are required. Together with the possible mechanism as to how Fbx8-mediated
      ubiquitination interferes with the functions of Arf6, we propose that Fbx8
      provides a novel suppressive control of Arf6 activity through noncanonical
      ubiquitination. Our results indicate that dysfunction of Fbx8 expression may
      contribute to the invasiveness of some breast cancer cells.

PMID- 18094046
TI  - Derlin-1 facilitates the retro-translocation of cholera toxin.
AB  - Cholera toxin (CT) intoxicates cells by using its receptor-binding B subunit
      (CTB) to traffic from the plasma membrane to the endoplasmic reticulum (ER). In
      this compartment, the catalytic A1 subunit (CTA1) is unfolded by protein
      disulfide isomerase (PDI) and retro-translocated to the cytosol where it triggers
      a signaling cascade, leading to secretory diarrhea. How CT is targeted to the
      site of retro-translocation in the ER membrane to initiate translocation is
      unclear. Using a semipermeabilized-cell retro-translocation assay, we demonstrate
      that a dominant-negative Derlin-1-YFP fusion protein attenuates the ER-to-cytosol
      transport of CTA1. Derlin-1 interacts with CTB and the ER chaperone PDI as
      assessed by coimmunoprecipitation experiments. An in vitro membrane-binding assay
      showed that CTB stimulated the unfolded CTA1 chain to bind to the ER membrane.
      Moreover, intoxication of intact cells with CTB stabilized the degradation of a
      Derlin-1-dependent substrate, suggesting that CT uses the Derlin-1 pathway. These
      findings indicate that Derlin-1 facilitates the retro-translocation of CT. CTB
      may play a role in this process by targeting the holotoxin to Derlin-1, enabling
      the Derlin-1-bound PDI to unfold the A1 subunit and prepare it for transport.

PMID- 18094047
TI  - Intraflagellar transport and functional analysis of genes required for flagellum
      formation in trypanosomes.
AB  - Intraflagellar transport (IFT) is the bidirectional movement of protein complexes
      required for cilia and flagella formation. We investigated IFT by analyzing nine
      conventional IFT genes and five novel putative IFT genes (PIFT) in Trypanosoma
      brucei that maintain its existing flagellum while assembling a new flagellum.
      Immunostaining against IFT172 or expression of tagged IFT20 or green fluorescent
      protein GFP::IFT52 revealed the presence of IFT proteins along the axoneme and at
      the basal body and probasal body regions of both old and new flagella. IFT
      particles were detected by electron microscopy and exhibited a strict
      localization to axonemal microtubules 3-4 and 7-8, suggesting the existence of
      specific IFT tracks. Rapid (>3 microm/s) bidirectional intraflagellar movement of
      GFP::IFT52 was observed in old and new flagella. RNA interference silencing
      demonstrated that all individual IFT and PIFT genes are essential for new
      flagellum construction but the old flagellum remained present. Inhibition of IFTB
      proteins completely blocked axoneme construction. Absence of IFTA proteins
      (IFT122 and IFT140) led to formation of short flagella filled with IFT172,
      indicative of defects in retrograde transport. Two PIFT proteins turned out to be
      required for retrograde transport and three for anterograde transport. Finally,
      flagellum membrane elongation continues despite the absence of axonemal
      microtubules in all IFT/PIFT mutant.

PMID- 18094048
TI  - Polyunsaturated fatty acids influence synaptojanin localization to regulate
      synaptic vesicle recycling.
AB  - The lipid polyunsaturated fatty acids are highly enriched in synaptic membranes,
      including synaptic vesicles, but their precise function there is unknown.
      Caenorhabditis elegans fat-3 mutants lack long-chain polyunsaturated fatty acids
      (LC-PUFAs); they release abnormally low levels of serotonin and acetylcholine and
      are depleted of synaptic vesicles, but the mechanistic basis of these defects is
      unclear. Here we demonstrate that synaptic vesicle endocytosis is impaired in the
      mutants: the synaptic vesicle protein synaptobrevin is not efficiently retrieved
      after synaptic vesicles fuse with the presynaptic membrane, and the presynaptic
      terminals contain abnormally large endosomal-like compartments and synaptic
      vesicles. Moreover, the mutants have abnormally low levels of the
      phosphoinositide phosphatase synaptojanin at release sites and accumulate the
      main synaptojanin substrate phosphatidylinositol 4,5-bisphosphate at these sites.
      Both synaptobrevin and synaptojanin mislocalization can be rescued by providing
      exogenous arachidonic acid, an LC-PUFA, suggesting that the endocytosis defect is
      caused by LC-PUFA depletion. By showing that the genes fat-3 and synaptojanin act
      in the same endocytic pathway at synapses, our findings suggest that LC-PUFAs are
      required for efficient synaptic vesicle recycling, probably by modulating
      synaptojanin localization at synapses.

PMID- 18094049
TI  - A novel regulatory mechanism of myosin light chain phosphorylation via binding of
      14-3-3 to myosin phosphatase.
AB  - Myosin II phosphorylation-dependent cell motile events are regulated by myosin
      light-chain (MLC) kinase and MLC phosphatase (MLCP). Recent studies have revealed
      myosin phosphatase targeting subunit (MYPT1), a myosin-binding subunit of MLCP,
      plays a critical role in MLCP regulation. Here we report the new regulatory
      mechanism of MLCP via the interaction between 14-3-3 and MYPT1. The binding of 14
      3-3beta to MYPT1 diminished the direct binding between MYPT1 and myosin II, and
      14-3-3beta overexpression abolished MYPT1 localization at stress fiber.
      Furthermore, 14-3-3beta inhibited MLCP holoenzyme activity via the interaction
      with MYPT1. Consistently, 14-3-3beta overexpression increased myosin II
      phosphorylation in cells. We found that MYPT1 phosphorylation at Ser472 was
      critical for the binding to 14-3-3. Epidermal growth factor (EGF) stimulation
      increased both Ser472 phosphorylation and the binding of MYPT1-14-3-3. Rho-kinase
      inhibitor inhibited the EGF-induced Ser472 phosphorylation and the binding of
      MYPT1-14-3-3. Rho-kinase specific siRNA also decreased EGF-induced Ser472
      phosphorylation correlated with the decrease in MLC phosphorylation. The present
      study revealed a new RhoA/Rho-kinase-dependent regulatory mechanism of myosin II
      phosphorylation by 14-3-3 that dissociates MLCP from myosin II and attenuates
      MLCP activity.

PMID- 18094050
TI  - MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via
      CHIP-mediated ubiquitination.
AB  - McKusick-Kaufman syndrome (MKKS) is a recessively inherited human genetic disease
      characterized by several developmental anomalies. Mutations in the MKKS gene also
      cause Bardet-Biedl syndrome (BBS), a genetically heterogeneous disorder with
      pleiotropic symptoms. However, little is known about how MKKS mutations lead to
      disease. Here, we show that disease-causing mutants of MKKS are rapidly degraded
      via the ubiquitin-proteasome pathway in a manner dependent on HSC70 interacting
      protein (CHIP), a chaperone-dependent ubiquitin ligase. Although wild-type MKKS
      quickly shuttles between the centrosome and cytosol in living cells, the rapidly
      degraded mutants often fail to localize to the centrosome. Inhibition of
      proteasome functions causes MKKS mutants to form insoluble structures at the
      centrosome. CHIP and partner chaperones, including heat-shock protein
      (HSP)70/heat-shock cognate 70 and HSP90, strongly recognize MKKS mutants. Modest
      knockdown of CHIP by RNA interference moderately inhibited the degradation of
      MKKS mutants. These results indicate that the MKKS mutants have an abnormal
      conformation and that chaperone-dependent degradation mediated by CHIP is a key
      feature of MKKS/BBS diseases.

PMID- 18094051
TI  - Tumor necrosis factor alpha regulates responses to nerve growth factor, promoting
      neural cell survival but suppressing differentiation of neuroblastoma cells.
AB  - Although nerve growth factor (NGF) promotes survival of neurons, tumor necrosis
      factor alpha (TNF-alpha) contributes to cell death triggered by NGF depletion,
      through TNF-alpha receptor (TNFR) 1. In contrast to this effect, TNF-alpha can
      promote neural cell survival via TNF-alpha receptor TNFR2. Although these
      findings demonstrate pivotal roles of TNF-alpha and NGF in cell fate decisions,
      cross-talk between these signaling pathways has not been clarified. We find that
      NGF can induce TNF-alpha synthesis through the nuclear factor-kappaB
      transcription factor. This provides a new basis for examining the cross-talk
      between NGF and TNF-alpha. Inhibition of TNFR2 shows opposite effects on two
      downstream kinases of NGF, extracellular signal-regulated kinase (Erk) and Akt.
      It increases Erk activation by NGF, and this increased activation induces
      differentiation of neuroblastoma cell lines. Reciprocally, inhibition of TNFR2
      decreases Akt activation by NGF. Consistent with an essential role of Akt in
      survival signaling, inhibition of TNF-alpha signaling decreases NGF-dependent
      survival of neurons from rat dorsal root ganglia. Thus, NGF and NGF-induced TNF
      alpha cooperate to activate Akt, promoting survival of normal neural cells.
      However, the NGF-induced TNF-alpha suppresses Erk activation by NGF, blocking NGF
      induced differentiation of neuroblastoma cells. TNFR2 signaling could be a novel
      target to modulate cell responses to NGF.

PMID- 18094052
TI  - A lipid-mediated quality control process in the Golgi apparatus in yeast.
AB  - When heme biosynthesis is disrupted, the yeast Saccharomyces cerevisiae becomes
      unable to synthesize its major sterol, ergosterol, and desaturate fatty acids. We
      took advantage of this physiological peculiarity to evaluate the consequences of
      ergosterol and/or unsaturated fatty acid (UFA) depletions on the biogenesis of a
      model polytopic plasma membrane protein, the uracil permease Fur4p. We show that
      under UFA shortage, which results in low amounts of diunsaturated phospholipid
      species, and under ergosterol depletion, Fur4p is prematurely routed from the
      Golgi apparatus to the vacuolar lumen in a process that requires the ubiquitin
      ligase Rsp5p. Interestingly, this diversion is not correlated to Fur4p exclusion
      from detergent-resistant membranes. In an independent set of experiments, we show
      that Fur4p targeting to the plasma membrane depends on phosphatidylethanolamine
      amounts and more specifically on the propensity of this phospholipid to form a
      hexagonal phase. In light of recent literature, we propose a model in which
      ergosterol and diunsaturated phospholipid species maintain optimal membrane
      curvature for Fur4p to evade the Golgi quality control process and to be properly
      delivered to its normal destination.

PMID- 18094053
TI  - Shugoshin promotes sister kinetochore biorientation in Saccharomyces cerevisiae.
AB  - Chromosome segregation must be executed accurately during both mitotic and
      meiotic cell divisions. Sgo1 plays a key role in ensuring faithful chromosome
      segregation in at least two ways. During meiosis this protein regulates the
      removal of cohesins, the proteins that hold sister chromatids together, from
      chromosomes. During mitosis, Sgo1 is required for sensing the absence of tension
      caused by sister kinetochores not being attached to microtubules emanating from
      opposite poles. Here we describe a differential requirement for Sgo1 in the
      segregation of homologous chromosomes and sister chromatids. Sgo1 plays only a
      minor role in segregating homologous chromosomes at meiosis I. In contrast, Sgo1
      is important to bias sister kinetochores toward biorientation. We suggest that
      Sgo1 acts at sister kinetochores to promote their biorientation.

PMID- 18094054
TI  - CENP-O class proteins form a stable complex and are required for proper
      kinetochore function.
AB  - We previously identified a multisubunit complex (CENP-H/I complex) in
      kinetochores from human and chicken cells. We showed that the CENP-H/I complex is
      divided into three functional classes. In the present study, we investigated CENP
      O class proteins, which include CENP-O, -P, -Q, -R, and -50 (U). We created
      chicken DT40 cell knockouts of each of these proteins, and we found that all
      knockout lines were viable, but that they showed slow proliferation and mitotic
      defects. Kinetochore localization of CENP-O, -P, -Q, and -50 was interdependent,
      but kinetochore localization of these proteins was observed in CENP-R-deficient
      cells. A coexpression assay in bacteria showed that CENP-O, -P, -Q, and -50
      proteins form a stable complex that can associate with CENP-R. Phenotype analysis
      of knockout cells showed that all proteins except for CENP-R were required for
      recovery from spindle damage, and phosphorylation of CENP-50 was essential for
      recovery from spindle damage. We also found that treatment with the proteasome
      inhibitor MG132 partially rescued the severe mitotic phenotype observed in
      response to release from nocodazole block in CENP-50-deficient cells. This
      suggests that CENP-O class proteins are involved in the prevention of premature
      sister chromatid separation during recovery from spindle damage.

PMID- 18094055
TI  - The interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of
      tight junctions and adherens junctions.
AB  - The assembly of tight junctions (TJs) and adherens junctions (AJs) is regulated
      by the transport of integral TJ and AJ proteins to and/or from the plasma
      membrane (PM) and it is tightly coordinated in epithelial cells. We previously
      reported that Rab13 and a junctional Rab13-binding protein (JRAB)/molecule
      interacting with CasL-like 2 (MICAL-L2) mediated the endocytic recycling of an
      integral TJ protein occludin and the formation of functional TJs. Here, we
      investigated the role of Rab13 and JRAB/MICAL-L2 in the transport of other
      integral TJ and AJ proteins claudin-1 and E-cadherin to the PM by using a Ca(2+)
      switch model. Although knockdown of Rab13 specifically suppressed claudin-1 and
      occludin but not E-cadherin transport, knockdown of JRAB/MICAL-L2 and expression
      of its Rab13-binding domain (JRAB/MICAL-L2-C) inhibited claudin-1, occludin, and
      E-cadherin transport. We then identified Rab8 as another JRAB/MICAL-L2-C-binding
      protein. Knockdown of Rab8 inhibited the Rab13-independent transport of E
      cadherin to the PM. Rab8 and Rab13 competed with each other for the binding to
      JRAB/MICAL-L2 and functionally associated with JRAB/MICAL-L2 at the perinuclear
      recycling/storage compartments and PM, respectively. These results suggest that
      the interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of
      AJs and TJs.

PMID- 18094056
TI  - A novel site of action for alpha-SNAP in the SNARE conformational cycle
      controlling membrane fusion.
AB  - Regulated exocytosis in neurons and neuroendocrine cells requires the formation
      of a stable soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) complex consisting of synaptobrevin-2/vesicle-associated membrane protein
      2, synaptosome-associated protein of 25 kDa (SNAP-25), and syntaxin 1. This
      complex is subsequently disassembled by the concerted action of alpha-SNAP and
      the ATPases associated with different cellular activities-ATPase N-ethylmaleimide
      sensitive factor (NSF). We report that NSF inhibition causes accumulation of
      alpha-SNAP in clusters on plasma membranes. Clustering is mediated by the binding
      of alpha-SNAP to uncomplexed syntaxin, because cleavage of syntaxin with
      botulinum neurotoxin C1 or competition by using antibodies against syntaxin SNARE
      motif abolishes clustering. Binding of alpha-SNAP potently inhibits Ca(2+)
      dependent exocytosis of secretory granules and SNARE-mediated liposome fusion.
      Membrane clustering and inhibition of both exocytosis and liposome fusion are
      counteracted by NSF but not when an alpha-SNAP mutant defective in NSF activation
      is used. We conclude that alpha-SNAP inhibits exocytosis by binding to the
      syntaxin SNARE motif and in turn prevents SNARE assembly, revealing an unexpected
      site of action for alpha-SNAP in the SNARE cycle that drives exocytotic membrane
      fusion.

PMID- 18094057
TI  - DYC-1, a protein functionally linked to dystrophin in Caenorhabditis elegans is
      associated with the dense body, where it interacts with the muscle LIM domain
      protein ZYX-1.
AB  - In Caenorhabditis elegans, mutations of the dystrophin homologue, dys-1, produce
      a peculiar behavioral phenotype (hyperactivity and a tendency to hypercontract).
      In a sensitized genetic background, dys-1 mutations also lead to muscle necrosis.
      The dyc-1 gene was previously identified in a genetic screen because its mutation
      leads to the same phenotype as dys-1, suggesting that the two genes are
      functionally linked. Here, we report the detailed characterization of the dyc-1
      gene. dyc-1 encodes two isoforms, which are expressed in neurons and muscles.
      Isoform-specific RNAi experiments show that the absence of the muscle isoform,
      and not that of the neuronal isoform, is responsible for the dyc-1 mutant
      phenotype. In the sarcomere, the DYC-1 protein is localized at the edges of the
      dense body, the nematode muscle adhesion structure where actin filaments are
      anchored and linked to the sarcolemma. In yeast two-hybrid assays, DYC-1
      interacts with ZYX-1, the homologue of the vertebrate focal adhesion LIM domain
      protein zyxin. ZYX-1 localizes at dense bodies and M-lines as well as in the
      nucleus of C. elegans striated muscles. The DYC-1 protein possesses a highly
      conserved 19 amino acid sequence, which is involved in the interaction with ZYX-1
      and which is sufficient for addressing DYC-1 to the dense body. Altogether our
      findings indicate that DYC-1 may be involved in dense body function and
      stability. This, taken together with the functional link between the C. elegans
      DYC-1 and DYS-1 proteins, furthermore suggests a requirement of dystrophin
      function at this structure. As the dense body shares functional similarity with
      both the vertebrate Z-disk and the costamere, we therefore postulate that
      disruption of muscle cell adhesion structures might be the primary event of
      muscle degeneration occurring in the absence of dystrophin, in C. elegans as well
      as vertebrates.

PMID- 18094059
TI  - Rewired to be thin? When exercise hits the brain.

PMID- 18094058
TI  - Inhibition of proteasome activity impairs centrosome-dependent microtubule
      nucleation and organization.
AB  - Centrosomes are dynamic organelles that consist of a pair of cylindrical
      centrioles, surrounded by pericentriolar material. The pericentriolar material
      contains factors that are involved in microtubule nucleation and organization,
      and its recruitment varies during the cell cycle. We report here that proteasome
      inhibition in HeLa cells induces the accumulation of several proteins at the
      pericentriolar material, including gamma-tubulin, GCP4, NEDD1, ninein,
      pericentrin, dynactin, and PCM-1. The effect of proteasome inhibition on
      centrosome proteins does not require intact microtubules and is reversed after
      removal of proteasome inhibitors. This accrual of centrosome proteins is
      paralleled by accumulation of ubiquitin in the same area and increased
      polyubiquitylation of nonsoluble gamma-tubulin. Cells that have accumulated
      centrosome proteins in response to proteasome inhibition are impaired in
      microtubule aster formation. Our data point toward a role of the proteasome in
      the turnover of centrosome proteins, to maintain proper centrosome function.

PMID- 18094060
TI  - Seasonal glucocorticoid responses to capture in wild free-living mammals.
AB  - We determined baseline and capture-induced glucocorticoid concentrations during
      two different seasons in three species of wild free-living rodents: brown
      lemmings (Lemmus trimucronatus), golden-mantled ground squirrels (Spermophilus
      saturatus), and yellow-pine chipmunks (Tamias amoenus). Initial blood samples
      were obtained within 3 min of capture, so that initial glucocorticoid levels
      reflect baseline titers of undisturbed animals. Animals were held for an
      additional 30 min, when a second blood sample was taken to measure stress-induced
      glucocorticoid titers. The primary glucocorticoid differed in each species.
      Lemmings secreted extremely large amounts of corticosterone (as high as 8,000
      ng/ml). These high concentrations were accompanied by high corticosterone-binding
      globulin capacity and resistance to negative feedback. Squirrels and chipmunks
      secreted a mixture of cortisol and corticosterone (10-400 ng/ml). In males of all
      three species and female squirrels and chipmunks, glucocorticoid levels were
      significantly elevated 30 min after capture. Baseline and 30-min glucocorticoid
      levels differed seasonally in each species. Levels were higher during summer
      (with no snow cover) than in spring (with approximately 60% snow cover) in female
      lemmings, higher during breeding than before hibernation in squirrels, and higher
      postreproductively than during breeding in chipmunks. Together, these data
      indicate that glucocorticoid responses to stress in these free-living species are
      similar to those in laboratory species, but the magnitude of the response appears
      to depend on life-history features specific to each species.

PMID- 18094061
TI  - Molecular detection and immunological localization of gill Na+/H+ exchanger in
      the dogfish (Squalus acanthias).
AB  - The dogfish (Squalus acanthias) can make rapid adjustments to gill acid-base
      transfers to compensate for internal acidosis/alkalosis. Branchial Na+/H+
      exchange (NHE) has been postulated as one mechanism driving the excretion of H+
      following acidosis. We have cloned gill cDNA that includes an open reading frame
      coding for a 770-residue protein most homologous (approximately 71%) to mammalian
      NHE2. RT-PCR revealed NHE2 transcripts predominantly in gill, stomach, rectal
      gland, intestine, and kidney. In situ hybridization with an antisense probe
      against NHE2 in gill sections revealed a strong mRNA signal from a subset of
      interlamellar and lamellae cells. We developed dogfish-specific polyclonal
      antibodies against NHE2 that detected a approximately 70-kDa protein in Western
      blots and immunologically recognized branchial cells having two patterns of
      protein expression. Cytoplasmic and apical NHE2 immunoreactivity were observed in
      cells coexpressing basolateral Na+-K+-ATPase. Other large ovoid cells more
      generally staining for NHE2 also were strongly positive for basolateral H+
      ATPase. Gill mRNA levels for NHE2 and H+-ATPase did not change following systemic
      acidosis (as measured by quantitative PCR 2 h after a 1- or 2-meq/kg acid
      infusion). These data indicate that posttranslational adjustments of NHE2 and
      other transport systems (e.g., NHE3) following acidosis may be of importance in
      the short-term pH adjustment and net branchial H+ efflux observed in vivo. NHE2
      may play multiple roles in the gills, involved with H+ efflux from acid-secreting
      cells, basolateral H+ reabsorption for pHi regulation, and in parallel with H+
      ATPase for the generation of HCO3(-) in base-secreting cells.

PMID- 18094062
TI  - Passive leg movement enhances interstitial VEGF protein, endothelial cell
      proliferation, and eNOS mRNA content in human skeletal muscle.
AB  - The present study used passive limb movement as an experimental model to study
      the effect of increased blood flow and passive stretch, without enhanced
      metabolic demand, in young healthy male subjects. The model used was 90 min of
      passive movement of the leg leading to a 2.8-fold increase (P < 0.05) in blood
      flow without a significant enhancement in oxygen uptake. Muscle interstitial
      fluid was sampled with microdialysis technique and analyzed for vascular
      endothelial growth factor (VEGF) protein and for the effect on endothelial cell
      proliferation. Biopsies obtained from the musculus vastus lateralis were analyzed
      for mRNA content of VEGF, endothelial nitric oxide synthase (eNOS), and matrix
      metalloproteinase-2 (MMP-2). The passive leg movement caused an increase (P <
      0.05) in interstitial VEGF protein concentration above rest (73 +/- 21 vs. 344 +/
      83 pg/ml). Addition of muscle dialysate to cultured endothelial cells revealed
      that dialysate obtained during leg movement induced a 3.2-fold higher
      proliferation rate (P < 0.05) than dialysate obtained at rest. Passive movement
      also enhanced (P < 0.05) the eNOS mRNA level fourfold above resting levels. VEGF
      mRNA and MMP-2 mRNA levels were unaffected. The results show that a session of
      passive leg movement, elevating blood flow and causing passive stretch, augments
      the interstitial concentrations of VEGF, the proliferative effect of interstitial
      fluid, and eNOS mRNA content in muscle tissue. We propose that enhanced blood
      flow and passive stretch are positive physiological stimulators of factors
      associated with capillary growth in human muscle.

PMID- 18094063
TI  - Reduced volume but increased training intensity elevates muscle Na+-K+ pump
      alpha1-subunit and NHE1 expression as well as short-term work capacity in humans.
AB  - The present study examined muscle adaptations and alterations in work capacity in
      endurance-trained runners after a change from endurance to sprint training.
      Fifteen runners were assigned to either a sprint training (ST, n = 8) or a
      control (CON, n = 7) group. ST replaced their normal training by 30-s sprint runs
      three to four times a week, whereas CON continued the endurance training
      (approximately 45 km/wk). After the 4-wk sprint period, the expression of the
      muscle Na+-K+ pump alpha1-subunit and Na+/H+-exchanger isoform 1 was 29 and 30%
      higher (P < 0.05), respectively. Furthermore, plasma K+ concentration was reduced
      (P < 0.05) during repeated intense running. In ST, performance in a 30-s sprint
      test, Yo-Yo intermittent recovery test, and two supramaximal exhaustive runs was
      improved (P < 0.05) by 7, 19, 27, and 19%, respectively, after the sprint
      training period, whereas pulmonary maximum oxygen uptake and 10-k time were
      unchanged. No changes in CON were observed. The present data suggest a role of
      the Na+-K+ pump in the control of K+ homeostasis and in the development of
      fatigue during repeated high-intensity exercise. Furthermore, performance during
      intense exercise can be improved and endurance performance maintained even with a
      reduction in training volume if the intensity of training is very high.

PMID- 18094064
TI  - Activation of 5-HT1A receptors in medullary raphe disrupts sleep and decreases
      shivering during cooling in the conscious piglet.
AB  - Activation of 5-HT1A receptors in the medullary raphe decreases sympathetically
      mediated brown adipose tissue (BAT) thermogenesis and peripheral vasoconstriction
      when previously activated with leptin, LPS, prostaglandins, or cooling. It is not
      known whether shivering is also modulated by medullary raphe 5-HT1A receptors. We
      previously showed in conscious piglets that activation of 5-HT1A receptors with
      (+/-)-8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT) in the
      paragigantocellularis lateralis (PGCL), a medullary region lateral to the raphe
      that contains substantial numbers of 5-HT neurons, eliminates rapid eye movement
      (REM) sleep and decreases shivering in a cold environment, but does not attenuate
      peripheral vasoconstriction. Hoffman JM, Brown JW, Sirlin EA, Benoit AM, Gill WH,
      Harris MB, Darnall RA. Am J Physiol Regul Integr Comp Physiol 293: R518-R527,
      2007. We hypothesized that, during cooling, activation of 5-HT1A receptors in the
      medullary raphe would also eliminate REM sleep and, in contrast to activation of
      5-HT1A receptors in the PGCL, would attenuate both shivering and peripheral
      vasoconstriction. In a continuously cool environment, dialysis of 8-OH-DPAT into
      the medullary raphe resulted in alternating brief periods of non-REM sleep and
      wakefulness and eliminated REM sleep, as observed when 8-OH-DPAT is dialyzed into
      the PGCL. Moreover, both shivering and peripheral vasoconstriction were
      significantly attenuated after 8-OH-DPAT dialysis into the medullary raphe. The
      effects of 8-OH-DPAT were prevented after dialysis of the selective 5-HT1A
      receptor antagonist WAY-100635. We conclude that, during cooling, exogenous
      activation of 5-HT1A receptors in the medullary raphe decreases both shivering
      and peripheral vasoconstriction. Our data are consistent with the hypothesis that
      neurons expressing 5-HT1A receptors in the medullary raphe facilitate spinal
      motor circuits involved in shivering, as well as sympathetic stimulation of other
      thermoregulatory effector mechanisms.

PMID- 18094065
TI  - Prior hypoglycemia enhances glucose responsiveness in some ventromedial
      hypothalamic glucosensing neurons.
AB  - Antecedent insulin-induced hypoglycemia (IIH) reduces adrenomedullary responses
      (AMR) to subsequent bouts of hypoglycemia. The ventromedial hypothalamus [VMH:
      arcuate (ARC) + ventromedial nuclei] contains glucosensing neurons, which are
      thought to be mediators of these AMR. Since type 1 diabetes mellitus often begins
      in childhood, we used juvenile (4- to 5-wk-old) rats to demonstrate that a single
      bout of IIH (5 U/kg sc) reduced plasma glucose by 24% and peak epinephrine by 59%
      1 day later. This dampened AMR was associated with 46% higher mRNA for VMH
      glucokinase, a key mediator of neuronal glucosensing. Compared with neurons from
      saline-injected rats, ventromedial nucleus glucose-excited neurons from insulin
      injected rats demonstrated a leftward shift in their glucose responsiveness (EC50
      = 0.45 and 0.10 mmol/l for saline and insulin, respectively, P = 0.05) and a 31%
      higher maximal activation by glucose (P = 0.05), although this maximum occurred
      at a higher glucose concentration (saline, 0.7 vs. insulin, 1.5 mmol/l). Although
      EC50 values did not differ, ARC glucose-excited neurons had 19% higher maximal
      activation, which occurred at a lower glucose concentration in insulin- than
      saline-injected rats (saline, 2.5 vs. insulin, 1.5 mmol/l). In addition, ARC
      glucose-inhibited neurons from insulin-injected rats were maximally inhibited at
      a fivefold lower glucose concentration (saline, 2.5 vs. insulin, 0.5 mmol/l),
      although this inhibition declined at >0.5 mmol/l glucose. These data suggest that
      the increased VMH glucokinase after IIH may contribute to the increased
      responsiveness of VMH glucosensing neurons to glucose and the associated blunting
      of the AMR.

PMID- 18094066
TI  - Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive
      oxygen species.
AB  - The cardiometabolic syndrome (CMS), with its increased risk for cardiovascular
      disease (CVD), nonalcoholic fatty liver disease (NAFLD), and chronic kidney
      disease (CKD), has become a growing worldwide health problem. Insulin resistance
      is a key factor for the development of the CMS and is strongly related to
      obesity, hyperlipidemia, hypertension, type 2 diabetes mellitus (T2DM), CKD, and
      NAFLD. Insulin resistance in skeletal muscle is particularly important since it
      is normally responsible for more than 75% of all insulin-mediated glucose
      disposal. However, the molecular mechanisms responsible for skeletal muscle
      insulin resistance remain poorly defined. Accumulating evidence indicates that
      low-grade chronic inflammation and oxidative stress play fundamental roles in the
      development of insulin resistance, and inflammatory cytokines likely contribute
      to the link between inflammation, oxidative stress, and skeletal muscle insulin
      resistance. Understanding the mechanisms by which skeletal muscle tissue develops
      resistance to insulin will provide attractive targets for interventions, which
      may ultimately curb this serious problem. This review is focused on the effects
      of inflammatory cytokines and oxidative stress on insulin signaling in skeletal
      muscle and consequent development of insulin resistance.

PMID- 18094067
TI  - Long-term modulation of tyrosine hydroxylase activity and expression by
      endothelin-1 and -3 in the rat anterior and posterior hypothalamus.
AB  - Brain catecholamines are involved in the regulation of biological functions,
      including cardiovascular activity. The hypothalamus presents areas with high
      density of catecholaminergic neurons and the endothelin system. Two hypothalamic
      regions intimately related with the cardiovascular control are distinguished: the
      anterior (AHR) and posterior (PHR) hypothalamus, considered to be
      sympathoinhibitory and sympathoexcitatory regions, respectively. We previously
      reported that endothelins (ETs) are involved in the short-term tyrosine
      hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for
      catecholaminergic transmission and is tightly regulated by well-characterized
      mechanisms. In the present study, we sought to establish the effects and
      underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed
      that in the AHR, ETs decreased TH activity through ET(B) receptor activation
      coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also
      reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely,
      in the PHR, ETs increased TH activity through a G protein-coupled receptor,
      likely an atypical ET receptor or the ET(C) receptor, which stimulated the
      phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also
      increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the
      enzyme. These findings support that ETs are involved in the long-term regulation
      of TH activity, leading to reduced sympathoinhibition in the AHR and increased
      sympathoexcitation in the PHR. Present and previous studies may partially explain
      the cardiovascular effects produced by ETs when applied to the brain.

PMID- 18094068
TI  - Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization
      through manipulation of the CD26 system.
AB  - Cyclosporin A (CsA) improves the success rate of transplantation. The
      CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing
      endothelial progenitor cells (EPCs) from bone marrow. This study investigated
      whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization.
      C57BL/6 mice were divided into control and CsA-treated groups. Before and after
      hindlimb ischemia was induced, circulating EPC number and serum levels of
      different cytokines were measured. Compared with the controls, CsA treatment
      significantly increased the blood levels of stroma-derived factor-1alpha and stem
      cell factor after ischemic stress (P < 0.001). The CsA group displayed a
      significant increase in the number of circulating EPCs (sca-1+KDR+ and c
      kit+CD31+ EPCs, both P < 0.05). In vivo, CsA caused a significant increase in the
      numbers of EPCs incorporated into the Matrigel and ischemic limbs (P < 0.05). In
      the peripheral blood, CsA significantly decreased CD26+ cell numbers and
      attenuated the plasma CD26/DPP IV activity (P < 0.001). Furthermore, short-term
      CsA treatment significantly improved the perfusion of ischemic limbs and
      decreased the spontaneous digital amputation rate. In summary, CsA manipulates
      the mobilization of EPCs into the circulation via the CD26/DPP IV system. Short
      term CsA treatment has beneficial effects on angiogenesis of ischemic tissues.

PMID- 18094069
TI  - Maternal protein restriction leads to early life alterations in the expression of
      key molecules involved in the aging process in rat offspring.
AB  - Recent findings demonstrate that nutrition during the fetal and neonatal periods
      can affect the life span of an organism. Our previous studies in rodents using a
      maternal low protein diet have shown that limiting protein and growth during
      lactation [postnatal low protein (PLP group)] increases longevity, while in utero
      growth restriction (IUGR) followed by "catch up growth" (recuperated group)
      shortens life span. The aim of this study was to investigate mechanisms in early
      postnatal life that could underlie these substantial differences in longevity. At
      weaning, PLP animals had improved insulin sensitivity as suggested by lower
      concentrations of insulin required to maintain concentrations of glucose similar
      to those of the control group and significant upregulation of insulin receptor
      beta, IGF-1 receptor, Akt1, Akt2, and Akt phosphorylated at Ser 473 in the
      kidney. These animals also had significantly increased SIRT1 (mammalian sirtuin)
      expression. Expression of the antioxidant enzymes catalase, CuZnSOD, and
      glutathione peroxidase-1 was elevated in these animals. In contrast, recuperated
      animals had a significantly increased fasting glucose concentration, while
      insulin levels remained comparable to those of the control group suggesting
      relative insulin resistance. MnSOD expression was increased in these animals.
      These data suggest that early nutrition can lead to alterations in insulin
      sensitivity and antioxidant capacity very early in life, which may influence life
      span.

PMID- 18094070
TI  - Food deprivation-induced changes in body fat mobilization after neonatal
      monosodium glutamate treatment.
AB  - The reversal of obesity is a difficult feat at best and is a growing problem as
      the obesity epidemic increases worldwide. Considerable focus has been made on the
      arcuate nucleus (Arc) in the control of body and lipid mass and food intake. To
      test the role of the Arc in body fat mobilization, we compared the effects of
      food deprivation on white adipose tissue (WAT) mass in adult Siberian hamsters by
      making exocytotic lesions of the Arc via neonatal subcutaneous injections of
      monosodium glutamate (MSG). MSG-treated hamsters had significantly increased body
      mass, total and individual WAT pad masses, and serum leptin concentrations
      compared with their vehicle-injected counterparts. MSG produced marked reductions
      in Arc Nissl staining, tyrosine hydroxylase-immunoreactive (ir) neurons, and
      neuropeptide Y (NPY)- and agouti-related protein (AgRP)-ir fibers compared with
      controls. MSG significantly decreased hypothalamic paraventricular nucleus (PVN)
      NPY- and AgRP fiber-ir compared with controls, likely because of Arc projections
      to this nucleus. MSG treatment also reduced area postrema (AP) tyrosine
      hydroxylase (TH)-ir fibers compared with controls. MSG treatment did not,
      however, block food deprivation-induced decreases in WAT pad mass compared with
      controls. Thus, despite considerable damage to the Arc and some of its
      projections to the PVN, as well as the AP, body fat was mobilized apparently
      normally, bringing into question the necessity of these structures for food
      deprivation-induced lipid mobilization. These data support recent evidence that
      chronically decerebrate rats, in which the forebrain is surgically isolated from
      the caudal brainstem, show normal food deprivation responses, including lipid
      mobilization.

PMID- 18094071
TI  - Human soleus single muscle fiber function with exercise or nutrition
      countermeasures during 60 days of bed rest.
AB  - The soleus muscle has been consistently shown to atrophy more than other leg
      muscles during unloading and is difficult to protect using various exercise
      countermeasure paradigms. However, the efficacy of aerobic exercise, a known
      stimulus for oxidative adaptations, has not been tested in combination with
      resistance exercise (RE), a known hypertrophic stimulus. We hypothesized that a
      concurrent exercise program (AE + RE) would preserve soleus fiber myosin heavy
      chain (MHC) I size and function during 60 days of bed rest. A secondary objective
      was to test the hypothesis that a leucine-enriched high protein diet would
      partially protect soleus single fiber characteristics. Soleus muscle biopsies
      were obtained before and after bed rest from a control (BR; n = 7), nutrition
      (BRN; n = 8), and exercise (BRE; n = 6) group. Single muscle fiber diameter
      (Dia), peak force (Po), contractile velocity, and power were studied. BR
      decreased (P < 0.05) MHC I Dia (-14%), Po (-38%), and power (-39%) with no change
      in contractile velocity. Changes in MHC I size (-13%) and contractile function
      (approximately 30%) from BRN were similar to BR. BRE decreased (P < 0.05) MHC I
      Dia (-13%) and Po (-23%), while contractile velocity increased (P < 0.05) 26% and
      maintained power. These soleus muscle data show 1) the AE + RE exercise program
      maintained MHC I power but not size and strength, and 2) the nutrition
      countermeasure did not benefit single fiber size and contractile function. The
      divergent response in size and functional MHC I soleus properties with the
      concurrent exercise program was a unique finding further highlighting the
      challenges of protecting the unloaded soleus.

PMID- 18094072
TI  - Seizure-induced up-regulation of P-glycoprotein at the blood-brain barrier
      through glutamate and cyclooxygenase-2 signaling.
AB  - Increased expression of drug efflux transporters at the blood-brain barrier
      accompanies epileptic seizures and complicates therapy with antiepileptic drugs.
      This study is concerned with identifying mechanistic links that connect seizure
      activity to increased P-glycoprotein expression at the blood-brain barrier. In
      this regard, we tested the hypothesis that seizures increase brain extracellular
      glutamate, which signals through an N-methyl-d-aspartate (NMDA) receptor and
      cyclooxygenase-2 (COX-2) in brain capillaries to increase blood-brain barrier P
      glycoprotein expression. Consistent with this hypothesis, exposing isolated rat
      or mouse brain capillaries to glutamate for 15 to 30 min increased P-glycoprotein
      expression and transport activity hours later. These increases were blocked by 5H
      dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate) (MK-801), an NMDA
      receptor antagonist, and by celecoxib, a selective COX-2 inhibitor; no such
      glutamate-induced increases were seen in brain capillaries from COX-2-null mice.
      In rats, intracerebral microinjection of glutamate caused locally increased P
      glycoprotein expression in brain capillaries. Moreover, using a pilocarpine
      status epilepticus rat model, we observed seizure-induced increases in capillary
      P-glycoprotein expression that were attenuated by administration of indomethacin,
      a COX inhibitor. Our findings suggest that brain uptake of some antiepileptic
      drugs can be enhanced through COX-2 inhibition. Moreover, they provide insight
      into one mechanism that underlies drug resistance in epilepsy and possibly other
      central nervous system disorders.

PMID- 18094074
TI  - A functional steroid-binding element in an ATP-binding cassette multidrug
      transporter.
AB  - The human breast cancer resistance protein is an ATP-binding cassette (ABC)
      multidrug transporter that affects the bioavailability of chemotherapeutic drugs
      and can confer drug resistance on cancer cells. It is the second member of the
      ABCG subfamily, other members of which are associated with human steroid
      disorders such as hypercholesterolemia, sitosterolemia, and atherosclerosis. The
      molecular bases of protein-steroid interactions in ABC transporters are unknown.
      Here, we identify a steroid-binding element in the membrane domain of ABCG2 with
      a similarity to steroid hormone/nuclear receptors. The element facilitates
      steroid hormone binding and mediates modulation of ABCG2 activity. The
      identification of this element might provide an opportunity for the development
      of new therapeutic ligands for ABCG2.

PMID- 18094073
TI  - Interferon beta augments tuberous sclerosis complex 2 (TSC2)-dependent inhibition
      of TSC2-null ELT3 and human lymphangioleiomyomatosis-derived cell proliferation.
AB  - Lymphangioleiomyomatosis (LAM), a rare pulmonary disorder, manifests as an
      abnormal neoplastic growth of smooth muscle-like cells within the lungs.
      Mutational inactivation of tumor suppressor tuberous sclerosis complex 2 (TSC2)
      in LAM constitutively activates the mammalian target of rapamycin (mTOR)/p70 S6
      kinase 1 (S6K1) signaling pathway and promotes neoplastic growth of LAM cells. In
      many cell types, type I interferon beta (IFNbeta) inhibits proliferation and
      induces apoptosis through signal transducers and activators of transcription
      (STAT)-dependent and STAT-independent signaling pathways, one of which is the
      mTOR/S6K1 signaling pathway. Our study shows that IFNbeta is expressed in LAM
      tissues and LAM-derived cell cultures; however, IFNbeta attenuates LAM-derived
      cell proliferation only at high concentrations, 100 and 1000 U/ml (IC(50) value
      for IFNbeta is 20 U/ml compared with 1 U/ml for normal human mesenchymal cells,
      human bronchus fibroblasts and human airway smooth muscle cells). Likewise,
      IFNbeta only attenuates proliferation of smooth muscle TSC2-null ELT3 cells.
      Analysis of IFNbeta signaling in LAM cells showed expression of IFNbeta receptor
      alpha (IFNbetaRalpha) and IFNbetaRbeta, activation and nuclear translocation of
      STAT1, and phosphorylation of STAT3 and p38 mitogen-activated protein kinase
      (MAPK), but IFNbeta had little effect on S6K1 activity. However, the re
      expression of TSC2 or inhibition of mTOR/S6K1 with rapamycin (sirolimus)
      augmented antiproliferative effects of IFNbeta in LAM and TSC2-null ELT3 cells.
      Our study demonstrates that IFNbeta-dependent activation of STATs and p38 MAPK is
      not sufficient to fully inhibit proliferation of cells with TSC2 dysfunction and
      that TSC2-dependent inhibition of mTOR/S6K1 cooperates with IFNbeta in inhibiting
      human LAM and TSC2-null ELT3 cell proliferation.

PMID- 18094075
TI  - Stretch induction of cyclooxygenase-2 expression in human urothelial cells is
      calcium- and protein kinase C zeta-dependent.
AB  - Prostanoid synthesis via cyclooxygenase (COX)-2 induction during urothelial
      stretch is central to nociception, inflammation, contractility, and proliferation
      caused by urinary tract obstruction. We used our primary human urothelial cell
      stretch model published previously to evaluate the signaling mechanisms
      responsible for stretch-induced COX-2 expression in urothelial cells. To
      determine intracytosolic calcium concentrations ([Ca(2+)](i)), primary human
      urothelial cells were grown on flexible membranes and loaded with Fura-2
      acetoxymethyl ester (AM). We determined [Ca(2+)](i) using a fluorescent scope
      during stretch. Additional cells were treated with 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA)-AM, stretched, and COX-2 mRNA and protein were
      evaluated by real-time polymerase chain reaction and immunoblotting. To evaluate
      protein kinase C (PKC) in this system, cells were stretched and fractionated into
      membrane, cytosol, and nucleus. Fractions were immunoblotted for PKCalpha, beta1,
      and zeta, the predominant isoforms in urothelial cells. We treated additional
      cells with increasing concentrations of either bisindolylmaleimide-I or a peptide
      PKC pseudosubstrate inhibitor, and COX-2 mRNA and protein were evaluated after
      stretching. Furthermore, we transfected urothelial cells with siRNA against each
      of the inducible PKC isoforms in these cells and evaluated the stretch-induced
      COX-2 response. Stretch of urothelial cells activated calcium flux and PKC
      translocation to membrane and nucleus. Pharmacological inhibition indicated that
      stretch-induced COX-2 expression is dependent on calcium and PKC, and biochemical
      knockdown experiments indicated that PKCzeta is the predominant isoform mediating
      stretch-induced COX-2 expression. Elucidating the signaling mechanism of stretch
      induced COX-2 expression may identify therapeutic targets.

PMID- 18094076
TI  - Induction of apoptosis by vinblastine via c-Jun autoamplification and p53
      independent down-regulation of p21WAF1/CIP1.
AB  - Vinblastine treatment in all cell lines examined causes a robust increase in c
      Jun protein expression and phosphorylation and a corresponding increase in
      activator protein-1 (AP-1) transcriptional activity. We show in KB-3 carcinoma
      cells that this is due to a strong autoamplification loop involving the proximal
      AP-1 site in the c-Jun promoter, resulting in highly increased c-Jun mRNA and c
      Jun protein. Inhibitors of RNA transcription and protein translation blocked both
      vinblastine-induced c-Jun expression and apoptotic cell death, suggesting that
      apoptosis is dependent, at least in part, on transcription/translation. Small
      interfering RNA (siRNA) to c-Jun was used to interrupt the amplification cycle
      and was found to be highly effective, reducing vinblastine-induced c-Jun
      expression at both the mRNA and protein levels by 90%. Apoptosis and caspase-3
      activation were significantly inhibited in c-Jun siRNA-treated cells. To uncover
      potential mechanisms of c-Jun-mediated cell death and protection by c-Jun siRNA,
      candidate target genes were examined. Chromatin immunoprecipitation revealed
      preferential association of c-Jun with the p21 (cyclin-dependent kinase
      inhibitor) gene promoter after vinblastine treatment. In KB-3 cells, which have
      compromised p53 function, and in p53-null cells but not in p53 wild-type cells,
      vinblastine caused down-regulation of p21 expression concomitant with increased c
      Jun expression, suggesting a role for c-Jun in negative regulation of the p21
      promoter independent of p53. These results provide strong evidence that c-Jun
      induction in response to vinblastine plays a proapoptotic role in part via down
      regulation of p21, promoting cycling and subsequent cell death of mitotically
      impaired cells.

PMID- 18094079
TI  - Stem cells in airway smooth muscle: state of the art.
AB  - Very little is known regarding the function, origin, and turnover of airway
      smooth muscle (ASM). In this article, we discuss the embryological development of
      ASM, and provide information regarding candidate mesenchymal ASM progenitor cell
      populations specifically in relation to airway remodeling. This review also
      highlights the current limitations in studying ASM biology, and underscores the
      need for novel molecular tools and markers that will refine our understanding of
      this cell type in lung homeostasis and disease.

PMID- 18094078
TI  - Embryological origin of airway smooth muscle.
AB  - Airway smooth muscle (SM) develops from local mesenchymal cells located around
      the tips of growing epithelial buds. These cells gradually displace from distal
      to proximal position alongside the bronchial tree, elongate, and begin to
      synthesize SM-specific proteins. Mechanical tension (either generated by cell
      spreading/elongation or stretch), as well as epithelial paracrine factors,
      regulates the process of bronchial myogenesis. The specific roles of many of
      these paracrine factors during normal lung development are currently unknown. It
      is also unknown how and if mechanical and paracrine signals integrate into a
      common myogenic pathway. Furthermore, as with vascular SM and other types of
      visceral SM, we are just beginning to elucidate the intracellular signaling
      pathways and the genetic program that controls lung myogenesis. Here we present
      what we have learned so far about the embryogenesis of bronchial muscle.

PMID- 18094081
TI  - Regulation of airway smooth muscle cell contractility by Ca2+ signaling and
      sensitivity.
AB  - Airway smooth muscle cell contraction is regulated by changes in intracellular
      Ca2+ concentration ([Ca2+]i) and the responsiveness of the airway smooth muscle
      cell to this Ca2+. The mechanism controlling [Ca2+]i primarily involves agonist
      induced release of Ca2+ from internal stores to generate Ca2+ oscillations. The
      extent of contraction correlates with the persistence and frequency of these Ca2+
      oscillations. The maintenance of the Ca2+ oscillations requires Ca2+ influx, but
      membrane depolarization appears to have a minor role in initiating or sustaining
      contraction. Contraction also requires agonist-induced Ca2+ sensitization, which
      is mediated mainly by decreases in myosin light-chain phosphatase activity.
      Although it is not clear if airway hyperresponsiveness associated with asthma
      results from the specific modulation of these Ca2+-based regulatory mechanisms,
      bronchodilators relax airways by both attenuating the Ca2+ oscillations and by
      decreasing the Ca2+ sensitivity.

PMID- 18094080
TI  - Calcium signaling in airway smooth muscle.
AB  - Contractility of airway smooth muscle requires elevation of intracellular calcium
      concentration. Under resting conditions, airway smooth muscle cells maintain a
      relatively low intracellular calcium concentration, and activation of the surface
      receptors by contractile agonists results in an elevation of intracellular
      calcium, culminating in contraction of the cell. The pattern of elevation of
      intracellular calcium brought about by agonists is a dynamic process and involves
      the coordinated activities of ion channels located in the plasma membrane and the
      sarcoplasmic reticulum. Among the signaling molecules involved in this dynamic
      calcium regulation in airway smooth muscle cells are inositol 1,4,5-trisphosphate
      and cyclic ADP-ribose, which mobilize calcium from the sarcoplasmic reticulum by
      acting via the inositol 1,4,5-trisphosphate and ryanodine receptors,
      respectively. In addition, calcium influx from the extracellular space is
      critical for the repletion of the intracellular calcium stores during activation
      of the cells by agonists. Calcium influx can occur via voltage- and receptor
      gated channels in the plasma membrane, as well as by influx that is triggered by
      depletion of the intracellular stores (i.e., store-operated calcium entry
      mechanism). Transient receptor potential proteins appear to mediate the calcium
      influx via receptor- and store-operated channels. Recent studies have shown that
      proinflammatory cytokines regulate the expression and activity of the pathways
      involved in intracellular calcium regulation, thereby contributing to airway
      smooth muscle cell hyperresponsiveness. In this review, we will discuss the
      specific roles of cyclic ADP-ribose/ryanodine receptor channels and transient
      receptor potential channels in the regulation of intracellular calcium in airway
      smooth muscle cells.

PMID- 18094083
TI  - Molecular mechanics of smooth muscle contractile proteins in airway
      hyperresponsiveness and asthma.
AB  - Airway hyperresponsiveness (AH) is a hallmark of asthma. The dynamics of the
      airway smooth muscle (SM) contraction, rather than its force-generating capacity,
      have been postulated to be key features of AH. Two mechanisms were proposed
      whereby an increased velocity of shortening (Vmax) of the airway SM leads to
      excessive bronchoconstriction. The first mechanism involves a greater Vmax during
      the initial portion of contraction, whereas the second mechanism implicates a
      greater Vmax after muscle stretches, such as after each tidal breath. This review
      focuses on the components of the contractile apparatus that have so far been
      reported to enhance the mechanics of the myosin molecular motor, thus leading to
      a greater Vmax. A greater activation of myosin, via increased phosphorylation of
      its regulatory light chain (LC20) by myosin light chain kinase, correlates with
      an increased Vmax in models of AH and in human asthmatic bronchial SM cells.
      However, poor correlations between these two parameters have also been reported
      in other models. A greater expression of the fast SM myosin heavy chain isoform
      [(+)insert or SM-B] also correlates with the greater Vmax measured in models of
      AH and in human asthmatic bronchial SM cells. However, the (+)insert isoform can
      only explain a twofold increase in Vmax, as extrapolated from its velocity of
      actin filament propulsion in the in vitro motility assay. Further considerations
      are given to the combination of these two factors with other components of the
      contractile machinery, thereby leading to the enhancement of airway SM function.

PMID- 18094082
TI  - Interactions of airway smooth muscle cells with their tissue matrix: implications
      for contraction.
AB  - The ability of airway smooth muscle to alter its stiffness and contractility in
      response to mechanical oscillation and stretch is critically important for the
      regulation of normal airway responsiveness during breathing. The properties of
      mechanical adaptation in airway smooth muscle are proposed to result from dynamic
      cytoskeletal processes outside of the actomyosin interaction. The actomyosin
      interaction and crossbridge cycling are viewed as components of a complex and
      integrated array of cytoskeletal events that occur during cell contraction. These
      events are orchestrated by macromolecular protein complexes that associate with
      the cytoplasmic domains of integrin proteins at the adhesion junctions between
      muscle cells and the extracellular matrix. According to this paradigm, these
      concerted cytoskeletal events are essential components of the process of active
      tension generation in airway smooth muscle, and also serve to adapt the shape and
      stiffness of the smooth muscle cell to its environment. Contractile stimuli
      initiate actin polymerization within the submembranous cortex of the airway
      smooth muscle cell that may serve to determine the cells shape and strengthen the
      membrane. The recruitment of structural proteins such as alpha-actinin to
      adhesion junctions fortifies the strength of the connections between membrane
      adhesion junctions and actin filaments. These processes create a strong and rigid
      cytoskeletal framework for the transmission of force generated by the interaction
      of myosin and actin filaments. This model for the regulation of airway smooth
      muscle function can provide novel perspectives to explain the normal physiologic
      behavior of the airways and pathophysiologic properties of the airways in asthma.

PMID- 18094085
TI  - Strange dynamics of a dynamic cytoskeleton.
AB  - A novel physical perspective of molecular interactions within the cytoskeleton of
      the airway smooth muscle cell may help to explain why the most efficacious of all
      known bronchodilatory agencies-a simple deep inspiration-becomes abrogated during
      the spontaneous asthma attack and leads thereby to excessive airway narrowing.
      This perspective invites us to think of airway smooth muscle not only
      biochemically as a nidus of traditional cell signaling and immune modulation or
      mechanically as a motor for generation of active forces but also physically as a
      phase of soft condensed matter that can restrict airway stretch and dilation.
      This is perhaps a risky path and is surely an unconventional one, but it is where
      the trail of evidence leads. This line of investigation is unlikely by itself to
      provide an asthma cure but will lead to a new conceptual framework without which
      novel pathways, unsuspected phase transitions, and unanticipated mechanisms of
      action of target molecules would almost surely remain hidden. Glassy dynamics of
      the cytoskeleton are likely to be important in a wide range of biological
      functions and disease processes, but had it not been for their preeminent role in
      bronchospasm, they might never have been discovered.

PMID- 18094084
TI  - Regulation of heterotrimeric G protein signaling in airway smooth muscle.
AB  - Heterotrimeric G proteins transduce signals from G protein-coupled receptors to
      regulate numerous signaling events and functions in airway smooth muscle (ASM).
      In this article, we detail the function and regulation of heterotrimeric G
      protein signaling in ASM. We further discuss recent advances in the development
      of experimental tools in the study of G protein signaling, and speculate how
      these tools might be used in therapeutic strategies that seek to mitigate
      bronchospasm and airway remodeling that occur in obstructive airway disease.

PMID- 18094086
TI  - Length adaptation of airway smooth muscle.
AB  - Many types of smooth muscle, including airway smooth muscle (ASM), are capable of
      generating maximal force over a large length range due to length adaptation,
      which is a relatively rapid process in which smooth muscle regains contractility
      after experiencing a force decrease induced by length fluctuation. Although the
      underlying mechanism is unclear, it is believed that structural malleability of
      smooth muscle cells is essential for the adaptation to occur. The process is
      triggered by strain on the cell cytoskeleton that results in a series of yet
      undefined biochemical and biophysical events leading to restructuring of the
      cytoskeleton and contractile apparatus and consequently optimization of the
      overlap between the myosin and actin filaments. Although length adaptability is
      an intrinsic property of smooth muscle, maladaptation of ASM could result in
      excessive constriction of the airways and the inability of deep inspirations to
      dilate them. In this article, we describe the phenomenon of length adaptation in
      ASM and some possible underlying mechanisms that involve the myosin filament
      assembly and disassembly. We discuss a possible role of maladaptation of ASM in
      the pathogenesis of asthma. We believe that length adaptation in ASM is mediated
      by specific proteins and their posttranslational regulations involving covalent
      modifications, such as phosphorylation. The discovery of these molecules and the
      processes that regulate their activity will greatly enhance our understanding of
      the basic mechanisms of ASM contraction and will suggest molecular targets to
      alleviate asthma exacerbation related to excessive constriction of the airways.

PMID- 18094087
TI  - Force fluctuation-induced relengthening of acetylcholine-contracted airway smooth
      muscle.
AB  - Superimposition of force fluctuations on contracted tracheal smooth muscle (TSM)
      has been used to simulate normal breathing. Breathing has been shown to reverse
      lung resistance of individuals without asthma and animals given methacholine to
      contract their airways; computed tomography scans also demonstrated bronchial
      dilation after a deep inhalation in normal volunteers. This reversal of airway
      resistance and bronchial constriction are absent (or much diminished) in
      individuals with asthma. Many studies have demonstrated that superimposition of
      force oscillations on contracted airway smooth muscle results in substantial
      smooth muscle lengthening. Subsequent studies have shown that this force
      fluctuation-induced relengthening (FFIR) is a physiologically regulated
      phenomenon. We hypothesized that actin filament length in the smooth muscle of
      the airways regulates FFIR of contracted tissues. We based this hypothesis on the
      observations that bovine TSM strips contracted using acetylcholine (ACh)
      demonstrated amplitude-dependent FFIR that was sensitive to mitogen-activated
      protein kinase (p38 MAPK) inhibition- an upstream regulator of actin filament
      assembly. We demonstrated latrunculin B (sequesters actin monomers thus
      preventing their assimilation into filaments resulting in shorter filaments)
      greatly increases FFIR and jasplakinolide (an actin filament stabilizer) prevents
      the effects of latrunculin B incubation on strips of contracted canine TSM. We
      suspect that p38 MAPK inhibition and latrunculin B predispose to shorter actin
      filaments. These studies suggest that actin filament length may be a key
      determinant of airway smooth muscle relengthening and perhaps breathing-induced
      reversal of agonist-induced airway constriction.

PMID- 18094088
TI  - Genetic differences in airway smooth muscle function.
AB  - The genetic basis for airway smooth muscle properties is poorly explored.
      Contraction and relaxation are altered in asthmatic airway smooth muscle, but the
      basis for the alterations and the role that muscle-specific susceptibility genes
      may play is largely unexplored. Alterations in the beta-adrenergic receptor,
      signaling pathways affecting inositol phosphate metabolism, adenylyl and guanylyl
      cyclase activity, and contractile proteins such as the myosin heavy chain are all
      suggested by experimental model systems. Significant changes in proliferative and
      secretory capacities of asthmatic smooth muscle are also demonstrated, but their
      genetic basis also requires elucidation. Certain asthma-related genes such as
      ADAM33, although potentially important for smooth muscle function, have been
      incompletely explored.

PMID- 18094089
TI  - Phenotype and functional plasticity of airway smooth muscle: role of caveolae and
      caveolins.
AB  - Airway smooth muscle (ASM) cells exhibit phenotype plasticity that is under
      control of external stimuli such as growth factors and the extracellular matrix,
      and is regulated by a network of intracellular signaling cascades that control
      transcription and protein translation of phenotype-specific genes. Phenotype
      plasticity underpins the ability of airway myocytes to contribute both to acute
      bronchospasm, and to the features of airway remodeling in chronic asthma. A
      feature of mature, contractile ASM cells is the presence of abundant caveolae,
      omega-shaped plasma membrane invaginations that develop from the association of
      lipid rafts with caveolin-1, a unique protein with structural and functional
      properties. Caveolae and caveolin-1 modulate signaling from receptors for growth
      factors and contractile agonists, and thus may modulate functional diversity of
      myocytes. Caveolin-1 appears to play a suppressive role in ASM cell
      proliferation, and orchestrates receptor-mediated signal transduction that
      regulates phenotype expression of ASM cells. Interestingly, in contractile
      myocytes caveolae are organized in close proximity to intracellular Ca2+-handling
      organelles, and are partitioned into discrete linear domains aligned with beta
      dystroglycan, a subunit of the actin-tethered dystrophin glycoprotein complex
      (DGC). Despite development of transgenic models to investigate caveolin biology,
      only superficial understanding of the role of these proteins in ASM phenotype
      expression and modulation of the functional responses of myocytes of a particular
      phenotype is available. This review summarizes mechanisms regulating ASM cell
      phenotype plasticity, and the role of caveolae as determinants of the functional
      diversity of ASM cells of a particular phenotypic state.

PMID- 18094090
TI  - Airway smooth muscle growth in asthma: proliferation, hypertrophy, and migration.
AB  - Increased airway smooth muscle mass is present in fatal and non-fatal asthma.
      However, little information is available regarding the cellular mechanism (i.e.,
      hyperplasia vs. hypertrophy). Even less information exists regarding the
      functional consequences of airway smooth muscle remodeling. It would appear that
      increased airway smooth muscle mass would tend to increase airway narrowing and
      airflow obstruction. However, the precise effects of increased airway smooth
      muscle mass on airway narrowing are not known. This review will consider the
      evidence for airway smooth muscle cell proliferation and hypertrophy in asthma,
      potential functional effects, and biochemical mechanisms.

PMID- 18094091
TI  - Migration of airway smooth muscle cells.
AB  - Migration of smooth muscle cells is a process fundamental to development of
      hollow organs, including blood vessels and the airways. Migration is also thought
      to be part of the response to tissue injury. It has also been suggested to
      contribute to airways remodeling triggered by chronic inflammation. In both
      nonmuscle and smooth muscle cells numerous external signaling molecules and
      internal signal transduction pathways contribute to cell migration. The review
      includes evidence for the functional significance of airway smooth muscle
      migration, a summary of promigratory and antimigratory agents, and summaries of
      important signaling pathways mediating migration. Important signaling pathways
      and effector proteins described include small G proteins, phosphatidylinositol 3
      kinases (PI3-K), Rho activated protein kinase (ROCK), p21-activated protein
      kinases (PAK), Src family tyrosine kinases, and mitogen-activated protein kinases
      (MAPK). These signaling modules control multiple critical effector proteins
      including actin nucleating, capping and severing proteins, myosin motors, and
      proteins that remodel microtubules. Actin filament remodeling, focal contact
      remodeling and propulsive force of molecular motors are all coordinated to move
      cells along gradients of chemical cues, matrix adhesiveness, or matrix stiffness.
      Airway smooth muscle cell migration can be modulated in vitro by drugs commonly
      used in pulmonary medicine including beta-adrenergic agonists and
      corticosteroids. Future studies of airway smooth muscle cell migration may
      uncover novel targets for drugs aimed at modifying airway remodeling.

PMID- 18094092
TI  - Airway smooth muscle cell as an inflammatory cell: lessons learned from
      interferon signaling pathways.
AB  - The present article will describe the potential role of airway smooth muscle
      (ASM) in mediating both deleterious/beneficial effects of interferons (IFNs) in
      asthma. First described as beneficial in treating the main features of asthma,
      the interplay between IFNs and ASM could explain their deleterious actions
      recently described in a number of different studies. Through multiple mechanisms,
      including the suppression of steroid action, the synergistic pro-inflammatory
      actions when combined with other cytokines, and the modulation of calcium
      metabolism, IFNs are now seen as critical mediators in the pathogenesis of
      asthma.

PMID- 18094093
TI  - Gene expression in asthmatic airway smooth muscle.
AB  - Airway smooth muscle abnormalities are central to the pathophysiology of asthma.
      These airway smooth muscle cell abnormalities may include changes in cell number,
      size, phenotype, or function. Gene expression studies performed using asthmatic
      airway smooth muscle cells represent one approach to identifying the
      abnormalities of airway smooth muscle that occur in asthma in vivo. However, due
      to the technical challenges involved, only two studies have been performed to
      date using freshly obtained tissue from subjects with asthma. The first of these
      studies suggested increased expression of myosin light-chain kinase in airway
      smooth muscle from patients with asthma, whereas the second study found no
      difference in myosin light-chain kinase expression, nor any difference in other
      markers of smooth muscle phenotype in asthma. Studies performed in cell culture
      through the application of gene expression microarrays to profile airway smooth
      muscle cells exposed to potential mediators of asthma yield more consistent
      results, including induction by IL-13 of tenascin, the H1 histamine receptor, and
      IL-13 receptor subunits. However, the significance of these microarray findings
      for smooth muscle function is uncertain. Furthermore, gene expression studies
      have a fundamental limitation in that many functional properties of airway smooth
      muscle are regulated at other levels (e.g., protein phosphorylation). Thus, gene
      expression studies ultimately must be integrated with other methodological
      approaches to adequately study airway smooth muscle in asthma in vivo.

PMID- 18094095
TI  - Airway myofibroblasts and their relationship with airway myocytes and
      fibroblasts.
AB  - Myofibroblasts are mesenchyme-derived cells responsible for tissue repair after
      injury. Resident populations of myofibroblasts are present throughout the lung.
      In addition, it is likely that myofibroblast progenitors (fibrocytes) can migrate
      to the lung from the circulation during injury. The relationship and
      interdependencies among myofibroblasts, fibroblasts, and myocytes within the
      airway wall remain poorly understood. Myofibroblasts are likely to be present in
      primary culture systems derived from airway wall tissue. The phenotyping of cells
      in such cultures is complicated by the lack of specific markers for these cell
      types. Important responses including migration, synthetic function, and the
      regulation of matrix, in the normal and asthmatic airway previously considered to
      be driven by airway myocytes may in fact at least in part be due to responses of
      myofibroblast populations.

PMID- 18094097
TI  - Barriers to and facilitators of walking and bicycling to school: formative
      results from the non-motorized travel study.
AB  - Barriers to and facilitators of walking and bicycling to school were explored
      through 12 focus groups made up of fourth- and fifth-grade students and their
      parents who lived near their respective schools. The barriers and facilitators
      reported by parents and children generally fell into one of three categories:
      intrapersonal and interpersonal characteristics of parents and children,
      environmental characteristics of the neighborhood, and environmental and policy
      characteristics of the school. Findings indicate that a supportive environment is
      a necessary but insufficient condition to increase walking and biking to school.
      Initiatives to increase active school travel may need to include multiple levels
      of intervention to be effective.

PMID- 18094094
TI  - Smooth muscle-like cells in pulmonary lymphangioleiomyomatosis.
AB  - Proliferation, migration, and differentiation of smooth muscle (SM)-like
      lymphangioleiomyomatosis (LAM) cells in the lungs are pathologic manifestations
      of pulmonary LAM, a rare lung disease predominantly afflicting women and
      exacerbated by pregnancy. LAM cells form nodules throughout the lung without any
      predominant localization, but can also form small cell clusters dispersed within
      lung parenchyma. LAM cells have the appearance of "immature" SM-like cells,
      irregularly distributed within the nodule in contrast to organized SM cell layers
      in airways and vasculature. Progressive growth of LAM cells leads to the cystic
      destruction of the lung parenchyma, obstruction of airways and lymphatics, and
      loss of pulmonary function. Pathogenetically, LAM occurs from somatic or genetic
      mutations of tumor suppressor genes tuberous sclerosis complex 1 (TSC1) or TSC2.
      The TSC1/TSC2 protein complex is an integrator of signaling networks regulated by
      growth factors, insulin, nutrients, and energy. The observation that the
      TSC1/TSC2 functions as a negative regulator of the mammalian target of rapamycin
      (mTOR)/p70 S6 kinase (S6K1) signaling pathway yielded the first rapamycin
      clinical trial for LAM. Although LAM is a rare lung disease, the elucidation of
      disease-relevant mechanisms of LAM will provide a better understanding of not
      only SM-like cell growth, migration, and differentiation in LAM but may also
      offer insights into other metabolic diseases such as cardiovascular diseases,
      diabetes, and cancer. In this article, we will summarize the progress made in our
      understanding of LAM, and we will focus on how dysregulation of TSC1/TSC2
      signaling results in abnormal proliferation and migration of SM-like LAM cells.

PMID- 18094098
TI  - Shared computational mechanism for tilt compensation accounts for biased
      verticality percepts in motion and pattern vision.
AB  - To determine the direction of object motion in external space, the brain must
      combine retinal motion signals and information about the orientation of the eyes
      in space. We assessed the accuracy of this process in eight laterally tilted
      subjects who aligned the motion direction of a random-dot pattern (30% coherence,
      moving at 6 degrees /s) with their perceived direction of gravity (motion
      vertical) in otherwise complete darkness. For comparison, we also tested the
      ability to align an adjustable visual line (12 degrees diameter) to the direction
      of gravity (line vertical). For small head tilts (<40 degrees ), systematic
      errors in either task were almost negligible. In contrast, tilts >60 degrees
      revealed a pattern of large systematic errors (often >30 degrees ) that was
      virtually identical in both tasks. Regression analysis confirmed that mean errors
      in the two tasks were closely related, with slopes close to 1.0 and correlations
      >0.89. Control experiments ruled out that motion settings were based on
      processing of individual single-dot paths. We conclude that the conversion of
      both motion direction and line orientation on the retina into a spatial frame of
      reference involves a shared computational strategy. Simulations with two spatial
      orientation models suggest that the pattern of systematic errors may be the
      downside of an optimal strategy for dealing with imperfections in the tilt signal
      that is implemented before the reference-frame transformation.

PMID- 18094099
TI  - Olfactory representations by Drosophila mushroom body neurons.
AB  - Learning and memory has been studied extensively in Drosophila using behavioral,
      molecular, and genetic approaches. These studies have identified the mushroom
      body as essential for the formation and retrieval of olfactory memories. We
      investigated odor responses of the principal neurons of the mushroom body, the
      Kenyon cells (KCs), in Drosophila using whole cell recordings in vivo. KC
      responses to odors were highly selective and, thus sparse, compared with those of
      their direct inputs, the antennal lobe projection neurons (PNs). We examined the
      mechanisms that might underlie this transformation and identified at least three
      contributing factors: excitatory synaptic potentials (from PNs) decay rapidly,
      curtailing temporal integration, PN convergence onto individual KCs is low (
      approximately 10 PNs per KC on average), and KC firing thresholds are high.
      Sparse activity is thought to be useful in structures involved in memory in part
      because sparseness tends to reduce representation overlaps. By comparing activity
      patterns evoked by the same odors across olfactory receptor neurons and across
      KCs, we show that representations of different odors do indeed become less
      correlated as they progress through the olfactory system.

PMID- 18094100
TI  - Short-latency crossed inhibitory responses in extensor muscles during locomotion
      in the cat.
AB  - During locomotion, contacting an obstacle generates a coordinated response
      involving flexion of the stimulated leg and activation of extensors
      contralaterally to ensure adequate support and forward progression. Activation of
      motoneurons innervating contralateral muscles (i.e., crossed extensor reflex) has
      always been described as an excitation, but the present paper shows that
      excitatory responses during locomotion are almost always preceded by a short
      period of inhibition. Data from seven cats chronically implanted with bipolar
      electrodes to record electromyography (EMG) of several hindlimb muscles
      bilaterally were used. A stimulating cuff electrode placed around the left tibial
      and left superficial peroneal nerves at the level of the ankle in five and two
      cats, respectively, evoked cutaneous reflexes during locomotion. During
      locomotion, short-latency ( approximately 13 ms) inhibitory responses were
      frequently observed in extensors of the right leg (i.e., contralateral to the
      stimulation), such as gluteus medius and triceps surae muscles, which were
      followed by excitatory responses ( approximately 25 ms). Burst durations of the
      left sartorius (Srt), a hip flexor, and ankle extensors of the right leg
      increased concomitantly in the mid- to late-flexion phases of locomotion with
      nerve stimulation. Moreover, the onset and offset of Srt and ankle extensor
      bursts bilaterally were altered in specific phases of the step cycle. Short
      latency crossed inhibition in ankle extensors appears to be an integral component
      of cutaneous reflex pathways in intact cats during locomotion, which could be
      important in synchronizing EMG bursts in muscles of both legs.

PMID- 18094101
TI  - Do we have a common mechanism for measuring time in the hundreds of millisecond
      range? Evidence from multiple-interval timing tasks.
AB  - In the present study we examined the performance variability of a group of 13
      subjects in eight different tasks that involved the processing of temporal
      intervals in the subsecond range. These tasks differed in their sensorimotor
      processing (S; perception vs. production), the modality of the stimuli used to
      define the intervals (M; auditory vs. visual), and the number of intervals (N;
      one or four). Different analytical techniques were used to determine the
      existence of a central or distributed timing mechanism across tasks. The results
      showed a linear increase in performance variability as a function of the interval
      duration in all tasks. However, this compliance of the scalar property of
      interval timing was accompanied by a strong effect of S, N, and M and the
      interaction between these variables on the subjects' temporal accuracy. Thus the
      performance variability was larger not only in perceptual tasks than that in
      motor-timing tasks, but also using visual rather than auditory stimuli, and
      decreased as a function of the number of intervals. These results suggest the
      existence of a partially overlapping distributed mechanism underlying the ability
      to quantify time in different contexts.

PMID- 18094102
TI  - A feedback model reproduces muscle activity during human postural responses to
      support-surface translations.
AB  - Although feedback models have been used to simulate body motions in human
      postural control, it is not known whether muscle activation patterns generated by
      the nervous system during postural responses can also be explained by a feedback
      control process. We investigated whether a simple feedback law could explain
      temporal patterns of muscle activation in response to support-surface
      translations in human subjects. Previously, we used a single-link inverted
      pendulum model with a delayed feedback controller to reproduce temporal patterns
      of muscle activity during postural responses in cats. We scaled this model to
      human dimensions and determined whether it could reproduce human muscle activity
      during forward and backward support-surface perturbations. Through optimization,
      we found three feedback gains (on pendulum acceleration, velocity, and
      displacement) and a common time delay that allowed the model to best match
      measured electromyographic (EMG) signals. For each muscle and each subject, the
      entire time courses of EMG signals during postural responses were well
      reconstructed in muscles throughout the lower body and resembled the solution
      derived from an optimal control model. In ankle muscles, >75% of the EMG
      variability was accounted for by model reconstructions. Surprisingly, >67% of the
      EMG variability was also accounted for in knee, hip, and pelvis muscles, even
      though motion at these joints was minimal. Although not explicitly required by
      our optimization, pendulum kinematics were well matched to subject center-of-mass
      (CoM) kinematics. Together, these results suggest that a common set of feedback
      signals related to task-level control of CoM motion is used in the temporal
      formation of muscle activity during postural control.

PMID- 18094103
TI  - Zinc potentiates neuronal nicotinic receptors by increasing burst duration.
AB  - Micromolar zinc potentiates neuronal nicotinic acetylcholine receptors (nAChRs)
      in a subtype-dependent manner. Zinc potentiates receptor function even at
      saturating agonist concentrations, without altering the receptor desensitization
      rate. Potentiation could occur through an increase in the number of available
      receptors, an increase in single-channel current amplitude, or an increase in
      single-channel open probability. To distinguish among these possibilities, we
      examined rat neuronal nAChRs expressed in Xenopus oocytes. Blockade of a large
      fraction of ACh activated alpha4beta4 or alpha4beta2 receptors by the open
      channel blocker hexamethonium failed to change the extent of potentiation by
      zinc, suggesting that zinc does not change the number of available receptors. The
      single-channel amplitudes of ACh (1 microM) activated alpha4beta4 receptors in
      outside-out patches were similar in the absence and the presence of 100 microM
      zinc (3.0 +/- 0.1 and 2.9 +/- 0.1 pA, respectively). To determine the effect of
      zinc on single-channel open probability, we examined alpha4beta4 receptors in
      cell-attached patches. The open probability at 100 nM ACh (0.011 +/- 0.002) was
      increased 4.5-fold by 100 microM zinc (0.050 +/- 0.008), accounting for most of
      the potentiation observed at the whole cell level. The increase in open
      probability was due to an increase in burst duration, which increased from 207 +/
      38 ms in the absence of zinc to 830 +/- 189 ms in the presence of zinc. Our
      results suggest that potentiation of neuronal nAChRs by zinc is due to a
      stabilization of the bursting states of the receptor.

PMID- 18094104
TI  - Effects of motor training on the recovery of manual dexterity after primary motor
      cortex lesion in macaque monkeys.
AB  - To investigate the effects of postlesion training on motor recovery, we compared
      the motor recovery of macaque monkeys that had received intensive motor training
      with those that received no training after a lesion of the primary motor cortex
      (M1). An ibotenic acid lesion in the M1 digit area resulted in impairment of hand
      function, with complete loss of digit movement. In the monkeys that had undergone
      intensive daily training (1 h/day, 5 days/wk) after the lesion, behavioral
      indexes used to evaluate manual dexterity recovered to the same level as in the
      prelesion period after 1 or 2 mo of postlesion training period. Relatively
      independent digit movements, including precision grip (prehension of a small
      object with finger-to-thumb opposition), were restored in the trained monkeys.
      Although the behavioral indexes of manual dexterity recovered to some extent in
      the monkeys without the postlesion training, they remained lower than those in
      the prelesion period until several months after M1 lesion. The untrained monkeys
      frequently used alternate grip strategies to grasp a small object with the
      affected hand, holding food pellets between the tip of the index finger and the
      dorsum of the thumb. These results suggest that the recovery after M1 lesion
      includes both use-dependent and use-independent processes and that the recovery
      of precision grip can be promoted by intensive use of the affected hand in
      postlesion training.

PMID- 18094105
TI  - D2-like dopamine receptors modulate SKCa channel function in subthalamic nucleus
      neurons through inhibition of Cav2.2 channels.
AB  - The activity patterns of subthalamic nucleus (STN) neurons are intimately related
      to motor function/dysfunction and modulated directly by dopaminergic neurons that
      degenerate in Parkinson's disease (PD). To understand how dopamine and dopamine
      depletion influence the activity of the STN, the functions/signaling
      pathways/substrates of D2-like dopamine receptors were studied using patch-clamp
      recording. In rat brain slices, D2-like dopamine receptor activation depolarized
      STN neurons, increased the frequency/irregularity of their autonomous activity,
      and linearized/enhanced their firing in response to current injection. Activation
      of D2-like receptors in acutely isolated neurons reduced transient outward
      currents evoked by suprathreshold voltage steps. Modulation was inhibited by a D2
      like receptor antagonist and occluded by voltage-dependent Ca2+ (Cav) channel or
      small-conductance Ca2+-dependent K+ (SKCa) channel blockers or Ca2+-free media.
      Because Cav channels are targets of G(i/o)-linked receptors, actions on step- and
      action potential waveform-evoked Cav channel currents were studied. D2-like
      receptor activation reduced the conductance of Cav2.2 but not Cav1 channels.
      Modulation was mediated, in part, by direct binding of Gbetagamma subunits
      because it was attenuated by brief depolarization. D2 and/or D3 dopamine
      receptors may mediate modulation because a D4-selective agonist was ineffective
      and mRNA encoding D2 and D3 but not D4 dopamine receptors was detectable. Brain
      slice recordings confirmed that SKCa channel-mediated action potential
      afterhyperpolarization was attenuated by D2-like dopamine receptor activation.
      Together, these data suggest that D2-like dopamine receptors potently modulate
      the negative feedback control of firing that is mediated by the functional
      coupling of Cav2.2 and SKCa channels in STN neurons.

PMID- 18094106
TI  - Presynaptic release probability is increased in hippocampal neurons from ASIC1
      knockout mice.
AB  - Acid-sensing ion channels (ASICs) are H(+)-gated channels that produce transient
      cation currents in response to extracellular acid. ASICs are expressed in neurons
      throughout the brain, and ASIC1 knockout mice show behavioral impairments in
      learning and memory. The role of ASICs in synaptic transmission, however, is not
      thoroughly understood. We analyzed the involvement of ASICs in synaptic
      transmission using microisland cultures of hippocampal neurons from wild-type and
      ASIC knockout mice. There was no significant difference in single action
      potential (AP)-evoked excitatory postsynaptic currents (EPSCs) between wild-type
      and ASIC knockout neurons. However, paired-pulse ratios (PPRs) were reduced and
      spontaneous miniature EPSCs (mEPSCs) occurred at a higher frequency in ASIC1
      knockout neurons compared with wild-type neurons. The progressive block of NMDA
      receptors by an open channel blocker, MK-801, was also faster in ASIC1 knockout
      neurons. The amplitude and decay time constant of mEPSCs, as well as the size and
      refilling of the readily releasable pool, were similar in ASIC1 knockout and wild
      type neurons. Finally, the release probability, which was estimated directly as
      the ratio of AP-evoked to hypertonic sucrose-induced charge transfer, was
      increased in ASIC1 knockout neurons. Transfection of ASIC1a into ASIC1 knockout
      neurons increased the PPRs, suggesting that alterations in release probability
      were not the result of developmental compensation within the ASIC1 knockout mice.
      Together, these findings demonstrate that neurons from ASIC1 knockout mice have
      an increased probability of neurotransmitter release and indicate that ASIC1a can
      affect presynaptic mechanisms of synaptic transmission.

PMID- 18094107
TI  - Ginsenoside Rg1 and aluminum hydroxide synergistically promote immune responses
      to ovalbumin in BALB/c mice.
AB  - The combined adjuvant effect of ginsenoside Rg1 and aluminum hydroxide (alum) on
      immune responses to ovalbumin (OVA) in mice was investigated. BALB/c mice were
      subcutaneously (s.c.) inoculated twice with OVA alone or in combination with Rg1,
      alum, or Rg1 plus alum. Samples were collected 2 weeks after the boosting for the
      measurement of anti-OVA immunoglobulin G (IgG) isotypes in sera and gamma
      interferon (IFN-gamma) and interleukin-5 (IL-5) produced in singular splenocyte
      cultures. Delayed-type hypersensitivity (DTH) responses were measured in mice
      immunized as described above. After 10 days, the mice were injected s.c. with OVA
      at the footpads. Thereafter, the thickness of the footpads was measured once
      daily for 5 days. The results indicated that alum enhanced mainly Th2 (IgG1 and
      IL-5) responses (P < 0.05), while Rg1 enhanced both Th1 (IgG1 and IL-5) and Th2
      (IgG2a, IFN-gamma, and DTH) responses (P < 0.05). The highest immune responses
      were found in the mice injected with OVA solution containing both alum and Rg1.
      In addition, the hemolytic activity of Rg1 was much lower than that of Quil A.
      Therefore, Rg1 deserves further studies in order to tailor desired immune
      responses when a mixed Th1/Th2 immune response is needed.

PMID- 18094108
TI  - Optimization of a type III secretion system-based Pseudomonas aeruginosa live
      vector for antigen delivery.
AB  - During the last few years, the use of type III secretion system-based bacterial
      vectors for immunotherapy purposes has been assessed in various applications. We
      showed that a type III secretion-based Pseudomonas aeruginosa vector delivering
      the ovalbumin (OVA) antigen induced an efficient specific CD8+ T-lymphocyte
      immune response against OVA-expressing cells. Because of the intrinsic toxicity
      of the vector, further virulence attenuation was needed. Therefore, we explored
      the effects of the deletion of quorum-sensing genes and the aroA gene toward
      toxicity and efficiency of the vector strain. The aroA mutation in our strain
      (making the strain auxotrophic for aromatic amino acids) conferred a strikingly
      reduced toxicity, with the bacterial lethal dose being more than 100 times higher
      than that of the parental strain. The quorum-sensing gene mutation alone was
      associated with a slightly reduced toxicity. In a prophylactic OVA-expressing
      melanoma mouse model, an OVA-delivering aroA-deficient mutant was the most
      efficient at a low dose (10(5)), but dose enhancement was not associated with a
      greater immune response. The quorum-sensing-deficient strain was the most
      efficient at a mild dose (10(6)), but this dose was close to the toxic dose.
      Combination of both mutations conferred the highest efficiency at an elevated
      dose (10(7)), in agreement with the known negative effects of quorum-sensing
      molecules upon T-cell activation. In conclusion, we have obtained a promising
      immunotherapy vector regarding toxicity and efficiency for further developments
      in both antitumor and anti-infectious strategies.

PMID- 18094109
TI  - Influence of maternal antibodies on efficacy of porcine circovirus type 2 (PCV2)
      vaccination to protect pigs from experimental infection with PCV2.
AB  - Due to the ubiquitous nature of porcine circovirus type 2 (PCV2) in the pig
      population and the increasing use of PCV2 vaccines in breeding herds, the
      majority of dams have been exposed to field PCV2 or PCV2 vaccines, resulting in
      piglets with varied levels of passively acquired PCV2 maternal antibodies. The
      objective of the current research was to investigate the influence of passively
      acquired anti-PCV2 antibodies on PCV2 vaccine efficacy. Sixty 26-day-old pigs
      were divided into four groups: vaccinated pigs with no maternal PCV2 antibodies
      at the time of vaccination (VAC-NEG; n = 9), vaccinated pigs with maternal PCV2
      antibodies at the time of vaccination (VAC-POS; n = 21), nonvaccinated pigs with
      no maternal antibodies at the time of challenge (NVAC-CNEG; n = 15), and
      nonvaccinated pigs with maternal antibodies at the time of challenge (NVAC-CPOS;
      n = 15). Vaccinations and challenges were performed on trial days 0 and 28,
      respectively, according to group designation. The pigs were monitored for
      clinical signs of disease daily and weighed weekly, and blood was collected
      weekly. All pigs were necropsied on trial day 49, and tissues were evaluated for
      macroscopic and microscopic lesions. Serum was evaluated using PCV2
      immunoglobulin G (IgG) and PCV2 IgM enzyme-linked immunosorbent assays,
      quantitative PCV2 PCR, and a serum PCV2 neutralizing antibody test. In comparison
      to NVAC-CPOS pigs, VAC-POS animals had significantly (P < 0.01) less severe
      microscopic PCV2-associated lymphoid lesions and significantly (P < 0.04) reduced
      PCV2 genomic copies in serum following PCV2 challenge. These results indicate
      that vaccination with Suvaxyn PCV2 One Dose reduces viremia and prevents
      microscopic lesions associated with PCV2 in the presence of maternal antibodies.

PMID- 18094110
TI  - Sequential analysis of Anaplasma phagocytophilum msp2 transcription in murine and
      equine models of human granulocytic anaplasmosis.
AB  - Anaplasma phagocytophilum causes human granulocytic anaplasmosis by inducing
      immunopathologic responses. Its immunodominant Msp2 protein is encoded by a
      family of >100 paralogs. Msp2 (msp2) expression modulates in the absence of
      immune pressure, and prolonged in vitro passage modulates in vivo virulence.
      Because programmed MSP2 expression occurs in Anaplasma marginale, we hypothesized
      a similar event in A. phagocytophilum in vivo, with specific Msp2 expression
      triggering immunopathologic injury or clinical manifestations of disease. We
      examined msp2 transcripts in 11 B6 mice and 6 horses inoculated with low- or high
      passage A. phagocytophilum Webster strain. Blood was sequentially obtained
      through 3 weeks postinfection for msp2 reverse transcription-PCR. Horses were
      additionally assessed for clinical manifestations, seroconversion, complete blood
      count, blood chemistry, and cytokine gene transcription. In both species, there
      was no consistent emergence of msp2 transcripts, and all 22 msp2 variants were
      detected in both passage groups. Clinical severity was much higher for high
      passage-infected than for low-passage-infected horses, preceded by higher levels
      of blood gamma interferon transcription on day 7. Antibody was first detected on
      day 7, and all horses seroconverted by day 22, with a trend toward lower antibody
      titers in low-passage-infected animals. Leukocyte and platelet counts were
      similar between experimental groups except on day 13, when low-passage-infected
      animals had more profound thrombocytopenia. These findings corroborate studies
      with mice, where msp2 diversity did not explain differences in hepatic
      histopathology, but differ from the paradigm of low-passage A. phagocytophilum
      causing more significant clinical illness. Alteration in transcription of msp2
      has no bearing on clinical disease in horses, suggesting the existence of a
      separate proinflammatory component differentially expressed with changing in
      vitro passage.

PMID- 18094111
TI  - Immunity to a self-derived, channel-forming peptide in the respiratory tract.
AB  - The channel-forming peptide NC-1130 was generated based on the amino acid
      sequence of the M2 segment of the spinal cord alpha-subunit of the glycine
      receptor and has been proposed as a therapeutic agent for anion channelopathies
      such as cystic fibrosis. Lysine adduction and amino acid substitutions at
      positions T19R and S22W of the peptide improved its performance as an ion
      channel. However, these modifications generated an altered self, potentially
      making this NC-1130 peptide immunogenic, which could preclude the repeated use of
      NC-1130 as a therapeutic agent. To measure the ability of NC-1130 to induce an
      immune response, it was administered nasally with or without cholera toxin (CT).
      The NC-1130 peptide, when given alone without adjuvant, induced very little
      peptide-specific immunity based on analyses of peptide-specific antibodies by
      enzyme-linked immunosorbent assay and enzyme-linked immunospot assay, induction
      of cytokine production, and delayed-type hypersensitivity (DTH) responses. The
      administration of NC-1130 with the mucosal adjuvant CT induced peptide-specific
      immunoglobulin G (IgG) antibodies and DTH responses and a Th2-dominant cytokine
      response. The coadministration of the strong mucosal adjuvant CT induced a
      systemic NC-1130-specific IgG response but not a mucosal peptide-specific
      antibody response. The lack of peptide-specific immunity and specifically mucosal
      immunity should allow repeated NC-1130 peptide applications to epithelial
      surfaces to correct anion channelopathies.

PMID- 18094112
TI  - Primary and secondary infections of Macaca fascicularis monkeys with Asian and
      American genotypes of dengue virus 2.
AB  - The goal of this study was to compare the immune response and the protection
      capacity induced by the dengue virus 2 (DENV-2) American and Asian genotypes in
      Macaca fascicularis monkeys. Animals were infected with American or Asian DENV-2
      strains and challenged 1 year later with a DENV-2 Asian genotype strain. The
      viremia and monkey antibody levels were similar for the different strains after
      primary and secondary infection; however, the functionality of the antibody
      response was different. A limited viral replication was demonstrated after the
      secondary infection in all the monkeys. No virus was isolated in tissue culture,
      while reverse transcription-PCR showed a late positive reaction in four of five
      challenged monkeys. The immunoglobulin M response pattern and the detection of
      antibodies to specific proteins by Western blotting supported the protection
      data. Despite the demonstration of the protective effect after homologous
      challenge, a strong anamnestic antibody response was observed.

PMID- 18094113
TI  - Vaccination against Pseudomonas aeruginosa pneumonia in immunocompromised mice.
AB  - Immunocompromised patients are highly susceptible to infection with Pseudomonas
      aeruginosa. Our laboratory previously showed that intranasal administration of an
      attenuated Salmonella strain expressing the P. aeruginosa lipopolysaccharide O
      antigen was effective in clearing bacteria and preventing mortality in wild-type
      mice after intranasal challenge. We were interested in investigating the efficacy
      of this vaccine strategy in immunocompromised mice. Mice rendered leukopenic or
      neutropenic by intraperitoneal treatment with cyclophosphamide (Cy) or RB6-8C5
      antibody, respectively, were more susceptible to P. aeruginosa pneumonia than
      their nontreated counterparts, demonstrating 50% lethal doses several logs lower
      than that in wild-type mice. This hypersusceptiblity was also associated with
      bacterial dissemination to the liver and spleen and increased lung permeability
      in Cy mice. Vaccination of the mice prior to treatment resulted in better
      survival and lower bacterial loads compared to vector-immunized mice. Although
      the treatments had no effect on antibody titers, this level of protection was
      still lower than that seen in untreated vaccinated mice. Administration of
      antibodies directly to the site of infection at the time of bacterial delivery
      prolonged survival and lowered bacterial loads in the immunocompromised mice.
      These results demonstrate the importance of white blood cells while still
      suggesting a critical role for antibodies in protection against P. aeruginosa
      infection.

PMID- 18094114
TI  - Production of recombinant antigens of Ureaplasma parvum serotypes 3 and 6 for
      development of a serological assay.
AB  - Recombinant antigens of Ureaplasma parvum serotypes 3 and 6 were produced in
      order to develop a serological assay for Ureaplasma antibody detection. The genes
      of the multiple banded antigen (MBA) were amplified by PCR and cloned in a
      pTrcHis TOPO plasmid. Purified recombinant proteins were evaluated in Western
      blotting and enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies
      and human sera. Our approach was successful in the production of the recombinant
      MBAs (rMBAs) for serotypes 3 and 6. The antigens tested positive with serotype
      specific monoclonal antibodies in Western blotting and in ELISA. Prominent
      reactions were detected with the rMBAs and their homologous monoclonal
      antibodies. Strong cross-reactions were visible in ELISA between rMBA 3 and the
      monoclonal antibodies from the other U. parvum serotypes. A weak cross-reaction
      was seen with rMBA 3 and the monoclonal antibody from serotype 4. rMBA 6 showed
      cross-reaction only with the monoclonal antibody from U. parvum serotype 1. Fifty
      one percent of the sera obtained from culture-positive women reacted with one or
      both rMBAs. Only three (15%) of the sera from culture-negative women reacted with
      the rMBA. The positive reactions were observed only with rMBA 6. These
      preliminary tests showed the potential usefulness of the rMBAs produced for
      detecting an antibody response against Ureaplasma antigens.

PMID- 18094115
TI  - Differentiation of C2D macrophage cells after adoptive transfer.
AB  - C2D macrophage cells protect immunocompromised mice from experimentally induced
      pneumonias after intraperitoneal (i.p.) adoptive transfer. These macrophage cells
      are immature and display minimal activity in vitro. Therefore, we wanted to
      understand how adoptive transfer affected these cells. We believe that the in
      vivo environment affects the phenotypic and functional characteristics of
      macrophages that help maintain the physiological integrity of the host. To test
      this hypothesis, we characterized the trafficking patterns and cellular changes
      of the established macrophage C2D cell line after adoptive transfer. We examined
      phenotypic changes of the C2D macrophage cells in vivo with and without
      stimulation with gamma interferon (IFN-gamma). After in vivo i.p. adoptive
      transfer, C2D macrophage cells trafficked to the lungs, spleen, lymph nodes, and
      bone marrow of recipient mice. The cells were detected for as long as 2 months,
      and the cells expressed increased levels of CD11b, c-fms, and F4/80 on their
      surface, becoming more differentiated macrophages compared to cells maintained in
      vitro. Upon in vivo stimulation with IFN-gamma, c-fms levels decreased while Gr-1
      levels increased compared to in vivo, unstimulated, phosphate-buffered saline
      injected controls. These responses were independent of the genetic backgrounds of
      the recipient mice. These data support the hypothesis and indicate that C2D
      macrophage cells respond to in vivo signals that are absent during in vitro
      culture.

PMID- 18094116
TI  - Identification of 19 polymorphic major outer membrane protein genes and their
      immunogenic peptides in Ehrlichia ewingii for use in a serodiagnostic assay.
AB  - Ehrlichia ewingii, a tick-transmitted rickettsia previously known only as a
      canine pathogen, was recently recognized as a human pathogen. E. ewingii has yet
      to be cultivated, and there is no serologic test available to diagnose E. ewingii
      infection. Previously, a fragment (505 bp) of a single E. ewingii gene homologous
      to 1 of 22 genes encoding Ehrlichia chaffeensis immunodominant major outer
      membrane proteins 1 (OMP-1s)/P28s was identified. The purposes of the present
      study were to (i) determine the E. ewingii omp-1 gene family, (ii) determine each
      OMP-1-specific peptide, and (iii) analyze all OMP-1 synthesized peptides for
      antigenicity. Using nested touchdown PCR and a primer walking strategy, we found
      19 omp-1 paralogs in E. ewingii. These genes are arranged in tandem downstream of
      tr1 and upstream of secA in a 24-kb genomic region. Predicted molecular masses of
      the 19 mature E. ewingii OMP-1s range from 25.1 to 31.3 kDa, with isoelectric
      points of 5.03 to 9.80. Based on comparative sequence analyses among OMP-1s from
      E. ewingii and three other Ehrlichia spp., each E. ewingii OMP-1 oligopeptide
      that was predicted to be antigenic, bacterial surface exposed, unique in
      comparison to the other E. ewingii OMP-1s, and distinct from those of other
      Ehrlichia spp. was synthesized for use in an enzyme-linked immunosorbent assay.
      Plasmas from experimentally E. ewingii-infected dogs reacted significantly with
      most of the OMP-1-specific peptides, indicating that multiple OMP-1s were
      expressed and immunogenic in infected dogs. The results support the utility of
      the tailored OMP-1 peptides as E. ewingii serologic test antigens.

PMID- 18094117
TI  - An intact unfolded protein response in Trpt1 knockout mice reveals phylogenic
      divergence in pathways for RNA ligation.
AB  - Unconventional mRNA splicing by an endoplasmic reticulum stress-inducible
      endoribonuclease, IRE1, is conserved in all known eukaryotes. It controls the
      expression of a transcription factor, Hac1p/XBP-1, that regulates gene expression
      in the unfolded protein response. In yeast, the RNA fragments generated by Ire1p
      are ligated by tRNA ligase (Trl1p) in a process that leaves a 2'-PO4(2-) at the
      splice junction, which is subsequently removed by an essential 2'
      phosphotransferase, Tpt1p. However, animals, unlike yeast, have two RNA
      ligation/repair pathways that could potentially rejoin the cleaved Xbp-1 mRNA
      fragments. We report that inactivation of the Trpt1 gene, encoding the only known
      mammalian homolog of Tpt1p, eliminates all detectable 2'-phosphotransferase
      activity from cultured mouse cells but has no measurable effect on spliced Xbp-1
      translation. Furthermore, the relative translation rates of tyrosine-rich
      proteins is unaffected by the Trpt1 genotype, suggesting that the pool of
      (normally spliced) tRNA(Tyr) is fully functional in the Trpt1-/- mouse cells.
      These observations argue against the presence of a 2'-PO4(2-) at the splice
      junction of ligated RNA molecules in Trpt1-/- cells, and suggest that Xbp-1 and
      tRNA ligation proceed by distinct pathways in yeast and mammals.

PMID- 18094118
TI  - Mammalian 2',3' cyclic nucleotide phosphodiesterase (CNP) can function as a tRNA
      splicing enzyme in vivo.
AB  - Yeast and plant tRNA splicing entails discrete healing and sealing steps
      catalyzed by a tRNA ligase that converts the 2',3' cyclic phosphate and 5'-OH
      termini of the broken tRNA exons to 3'-OH/2'-PO4 and 5'-PO4 ends, respectively,
      then joins the ends to yield a 2'-PO4, 3'-5' phosphodiester splice junction. The
      junction 2'-PO4 is removed by a tRNA phosphotransferase, Tpt1. Animal cells have
      two potential tRNA repair pathways: a yeast-like system plus a distinctive
      mechanism, also present in archaea, in which the 2',3' cyclic phosphate and 5'-OH
      termini are ligated directly. Here we report that a mammalian 2',3' cyclic
      nucleotide phosphodiesterase (CNP) can perform the essential 3' end-healing steps
      of tRNA splicing in yeast and thereby complement growth of strains bearing lethal
      or temperature-sensitive mutations in the tRNA ligase 3' end-healing domain.
      Although this is the first evidence of an RNA processing function in vivo for the
      mammalian CNP protein, it seems unlikely that the yeast-like pathway is
      responsible for animal tRNA splicing, insofar as neither CNP nor Tpt1 is
      essential in mice.

PMID- 18094119
TI  - Puf1p acts in combination with other yeast Puf proteins to control mRNA
      stability.
AB  - The eukaryotic Puf proteins bind 3' untranslated region (UTR) sequence elements
      to regulate the stability and translation of their target transcripts, and such
      regulatory events are critical for cell growth and development. Several global
      genome analyses have identified hundreds of potential mRNA targets of the
      Saccharomyces cerevisiae Puf proteins; however, only three mRNA targets for these
      proteins have been characterized thus far. After direct testing of nearly 40
      candidate mRNAs, we established two of these as true mRNA targets of Puf-mediated
      decay in yeast, HXK1 and TIF1. In a novel finding, multiple Puf proteins,
      including Puf1p, regulate both of these mRNAs in combination. TIF1 mRNA decay can
      be stimulated individually by Puf1p and Puf5p, but the combination of both
      proteins is required for full regulation. This Puf-mediated decay requires the
      presence of two UGUA binding sites within the TIF1 3' UTR, with one site
      regulated by Puf5p and the other by both Puf1p and Puf5p. Alteration of the UGUA
      site in the tif1 3' UTR to more closely resemble the Puf3p binding site broadens
      the specificity to include regulation by Puf3p. The stability of the endogenously
      transcribed HXK1 mRNA, cellular levels of Hxk1 protein activity, and HXK1 3' UTR
      directed decay are affected by Puf1p and Puf5p as well as Puf4p. Together these
      results identify the first mRNA targets of Puf1p-mediated decay, describe similar
      yet distinct combinatorial control of two new target mRNAs by the yeast Puf
      proteins, and suggest the importance of direct testing to evaluate RNA-regulatory
      mechanisms.

PMID- 18094120
TI  - A-to-I editing sites are a genomically encoded G: implications for the
      evolutionary significance and identification of novel editing sites.
AB  - Ribonucleic acid (RNA) editing can extend transcriptomic and proteomic diversity
      by changing the identity of a particular codon. Genetic recoding as a result of
      adenosine-to-inosine (A-to-I) RNA editing can alter highly conserved or invariant
      coding positions in proteins. Interestingly, examples exist in which A-to-I
      editing sites in one species are fixed genomically as a G in a closely related
      species. Phylogenetic analysis indicates that G-to-A mutations at the DNA level
      may be corrected by post-transcriptional A-to-I RNA editing, while in turn, the
      edited I (G) may be hardwired into the genome, resulting in an A-to-G mutation.
      We propose a model in which nuclear A-to-I RNA editing acts as an evolutionary
      intermediate of genetic variation. We not only provide information on the
      mechanism behind the evolutionary acquisition of an A-to-I RNA editing site but
      also demonstrate how to predict nuclear A-to-I editing sites by identifying
      positions where an RNA editing event would maintain the conservation of a protein
      relative to its homologs in other species. We identified a novel edited site in
      the fourth exon of the cacophony transcript coding calcium channel alpha1 and
      verified it experimentally.

PMID- 18094121
TI  - Strand-specific 5'-O-methylation of siRNA duplexes controls guide strand
      selection and targeting specificity.
AB  - Small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide catalytic sequence
      specific cleavage of fully or nearly fully complementary target mRNAs or control
      translation and/or stability of many mRNAs that share 6-8 nucleotides (nt) of
      complementarity to the siRNA and miRNA 5' end. siRNA- and miRNA-containing
      ribonucleoprotein silencing complexes are assembled from double-stranded 21- to
      23-nt RNase III processing intermediates that carry 5' phosphates and 2-nt
      overhangs with free 3' hydroxyl groups. Despite the structural symmetry of a
      duplex siRNA, the nucleotide sequence asymmetry can generate a bias for preferred
      loading of one of the two duplex-forming strands into the RNA-induced silencing
      complex (RISC). Here we show that the 5'-phosphorylation status of the siRNA
      strands also acts as an important determinant for strand selection. 5'-O
      methylated siRNA duplexes refractory to 5' phosphorylation were examined for
      their biases in siRNA strand selection. Asymmetric, single methylation of siRNA
      duplexes reduced the occupancy of the silencing complex by the methylated strand
      with concomitant elimination of its off-targeting signature and enhanced off
      targeting signature of the phosphorylated strand. Methylation of both siRNA
      strands reduced but did not completely abolish RNA silencing, without affecting
      strand selection relative to that of the unmodified siRNA. We conclude that
      asymmetric 5' modification of siRNA duplexes can be useful for controlling
      targeting specificity.

PMID- 18094122
TI  - A genome-wide approach identifies distinct but overlapping subsets of cellular
      mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein
      complexes.
AB  - Messenger RNAs are associated with multiple RNA-binding proteins to form
      ribonucleoprotein (mRNP) complexes. These proteins are important regulators of
      the fate of their target mRNAs. In human cells, Staufen1 and Staufen2 proteins,
      coded by two different genes, are double-stranded RNA-binding proteins involved
      in several cellular functions including mRNA localization, translation, and
      decay. Although 51% identical, these proteins are nevertheless found in different
      RNA particles. In addition, differential splicing events generate Staufen2
      isoforms that only differ at their N-terminal extremities. In this paper, we used
      a genome-wide approach to identify and compare the mRNA targets of mammalian
      Staufen proteins. The mRNA content of Staufen mRNPs was identified by probing DNA
      microarrays with probes derived from mRNAs isolated from immunopurified Staufen
      containing complexes following transfection of HEK293T cells with Stau1(55)-HA,
      Stau2(59)-HA, or Stau2(62)-HA expressors. Our results indicate that 7% and 11% of
      the cellular RNAs expressed in HEK293T cells are found in Stau1- and in Stau2
      containing mRNPs, respectively. A comparison of Stau1- and Stau2-containing mRNAs
      identifies a relatively low percentage of common mRNAs; the percentage of common
      mRNAs highly increases when mRNAs in Stau2(59)-HA- and Stau2(62)-containing mRNPs
      are compared. There is a predominance of mRNAs involved in cell metabolism,
      transport, transcription, regulation of cell processes, and catalytic activity.
      All these subsets of mRNAs are mostly distinct from those associated with FMRP or
      IMP, although some mRNAs overlap. Consistent with a model of post-transcriptional
      gene regulation, our results show that Stau1- and Stau2-mRNPs associate with
      distinct but overlapping sets of cellular mRNAs.

PMID- 18094123
TI  - Factor requirements for translation initiation on the Simian picornavirus
      internal ribosomal entry site.
AB  - The Simian picornavirus type 9 (SPV9) 5'-untranslated region (5' UTR) has been
      predicted to contain an internal ribosomal entry site (IRES) with structural
      elements that resemble domains of hepacivirus/pestivirus (HP) IRESs. In vitro
      reconstitution of initiation confirmed that this 5' UTR contains an IRES and
      revealed that it has both functional similarities and differences compared to HP
      IRESs. Like HP IRESs, the SPV9 IRES bound directly to 40S subunits and eukaryotic
      initiation factor (eIF) 3, depended on the conserved domain IIId for ribosomal
      binding and consequently for function, and additionally required eIF2/initiator
      tRNA to yield 48S complexes that formed elongation-competent 80S ribosomes in the
      presence of eIF5, eIF5B, and 60S subunits. Toeprinting analysis revealed that
      eIF1A stabilized 48S complexes, whereas eIF1 induced conformational changes in
      the 40S subunit, likely corresponding to partial opening of the entry latch of
      the mRNA-binding channel, that were exacerbated by eIF3 and suppressed by eIF1A.
      The SPV9 IRES differed from HP IRESs in that its function was enhanced by
      eIF4A/eIF4F when the IRES was adjacent to the wild-type coding sequence, but was
      less affected by these factors or by a dominant negative eIF4A mutant when
      potentially less structured coding sequences were present. Exceptionally, this
      IRES promoted binding of initiator tRNA to the initiation codon in the P site of
      40S subunits independently of eIF2. Although these 40S/IRES/tRNA complexes could
      not form active 80S ribosomes, this constitutes a second difference between the
      SPV9 and HP IRESs. eIF1 destabilized the eIF2-independent ribosomal binding of
      initiator tRNA.

PMID- 18094124
TI  - eap Gene as novel target for specific identification of Staphylococcus aureus.
AB  - The cell surface-associated extracellular adherence protein (Eap) mediates
      adherence of Staphylococcus aureus to host extracellular matrix components and
      inhibits inflammation, wound healing, and angiogenesis. A well-characterized
      collection of S. aureus and non-S. aureus staphylococcal isolates (n = 813) was
      tested for the presence of the Eap-encoding gene (eap) by PCR to investigate the
      use of the eap gene as a specific diagnostic tool for identification of S.
      aureus. Whereas all 597 S. aureus isolates were eap positive, this gene was not
      detectable in 216 non-S. aureus staphylococcal isolates comprising 47 different
      species and subspecies of coagulase-negative staphylococci and non-S. aureus
      coagulase-positive or coagulase-variable staphylococci. Furthermore, non-S.
      aureus isolates did not express Eap homologs, as verified on the transcriptional
      and protein levels. Based on these data, the sensitivity and specificity of the
      newly developed PCR targeting the eap gene were both 100%. Thus, the unique
      occurrence of Eap in S. aureus offers a promising tool particularly suitable for
      molecular diagnostics of this pathogen.

PMID- 18094125
TI  - Simultaneous detection of Chlamydophila pneumoniae and Mycoplasma pneumoniae by
      use of molecular beacons in a duplex real-time PCR.
AB  - A real-time PCR was designed for detection of Chlamydophila pneumoniae and
      Mycoplasma pneumoniae such that each pathogen could be detected in a single tube
      and differentiated using molecular beacons marked with different fluorochromes.
      This duplex PCR, targeting the P1 adhesion gene for M. pneumoniae and the ompA
      gene for C. pneumoniae, was compared with two conventional PCR assays targeting
      the 16S rRNA gene and the ompA gene. A total of 120 clinical throat and
      nasopharyngeal swab samples were tested. DNA extraction was performed using an
      alkali denaturation/neutralization method, and real-time amplification,
      detection, and data analysis were performed using a Rotor-Gene 2000 real-time
      rotary analyzer (Corbett Life Science, Sydney, Australia). Using conventional PCR
      as a reference in an analysis of 120 samples, 13 of 14 samples positive for C.
      pneumoniae were detected by the novel real-time PCR. In an analysis of M.
      pneumoniae, 22 samples were positive in the conventional PCR and the novel assay
      detected 24 positive samples. When using the conventional PCR as a reference,
      sensitivity and specificity were 93% and 100%, respectively, for C. pneumoniae
      and 100% and 98%, respectively, for M. pneumoniae. With an overall agreement of
      98.8%, this suggests that performance of the new duplex real-time PCR is
      comparable to that of conventional PCR.

PMID- 18094126
TI  - Distribution of conjugative-plasmid-mediated 16S rRNA methylase genes among
      amikacin-resistant Enterobacteriaceae isolates collected in 1995 to 1998 and 2001
      to 2006 at a university hospital in South Korea and identification of conjugative
      plasmids mediating dissemination of 16S rRNA methylase.
AB  - The distribution of conjugative-plasmid-mediated 16S rRNA methylase genes among
      amikacin-resistant Enterobacteriaceae collected between 1995 and 1998 and between
      2001 and 2006 at a university hospital in South Korea was examined, and
      conjugative plasmids carrying the 16S rRNA methylase genes were characterized by
      PCR-based replicon typing and by determination of their antimicrobial resistance
      pattern. Among the 7,127 isolates, 463 isolates showed a high level of resistance
      to amikacin, and 218 of the 463 isolates transferred amikacin resistance by
      conjugation. Among the 218 isolates, armA was detected in 153 isolates (88
      Klebsiella pneumoniae, 28 Escherichia coli, 19 Enterobacter cloacae, and 6
      Serratia marcescens isolates and 12 isolates of other organisms), and rmtB was
      detected in 51 isolates (32 K. pneumoniae isolates, 18 E. coli isolates, and 1
      Citrobacter freundii isolate). The first appearance of armA was in 1997. The armA
      gene was carried by conjugative plasmids of replicon groups IncL/M, IncFIIAs,
      IncF, IncA/C, IncHI2, and Inc(unidentified) in 38, 20, 7, 9, 4, and 75 strains,
      respectively. The rmtB gene was carried by conjugative plasmids of groups IncA/C,
      IncF, and IncI1-Igamma in 43 strains, 7 strains, and 1 strain, respectively.
      Transconjugants that received the IncL/M plasmid carrying armA or the IncA/C
      plasmid carrying rmtB showed an additional resistance to cefotaxime.
      Transconjugants that received the IncFIIA plasmid or Inc(unidentified) plasmid
      carrying the armA gene showed an additional resistance to cefoxitin and a high
      MIC(50) (0.25 mg/liter) of ciprofloxacin. In conclusion, this study demonstrated
      that the dissemination of 16S rRNA methylase genes among the Enterobacteriaceae
      is mediated by conjugative plasmids of various incompatibility groups that confer
      resistance to multiple drugs, including aminoglycosides, extended-spectrum beta
      lactams, and/or quinolones.

PMID- 18094127
TI  - Development of PCR assays with nested primers specific for differential detection
      of three human anelloviruses and early acquisition of dual or triple infection
      during infancy.
AB  - We recently identified a novel human virus classifiable into a third group in the
      genus Anellovirus, tentatively designated torque teno midi virus (TTMDV), with a
      circular DNA genome of 3.2 kb and genomic organization resembling those of torque
      teno virus (TTV) (3.8 to 3.9 kb) and torque teno mini virus (TTMV) (2.8 to 2.9
      kb). TTMDV was characterized by extreme genetic diversity similar to the TTV and
      TTMV genomes. Taking advantage of universal and virus species-specific primers
      derived from a highly conserved area located just downstream of the TATA box of
      the TTV, TTMDV, and TTMV genomes, a PCR method with simultaneous amplification of
      the genomic DNAs of these three anelloviruses in the first round and subsequent
      differential amplifications of these viruses in the second round was developed.
      High prevalence of TTMDV viremia was seen in adults (75/100 [75%]), comparable
      with the prevalences of TTV viremia (100%) and TTMV viremia (82%). Although none
      of 10 cord blood samples had detectable TTV, TTMDV, and TTMV DNAs, the
      prevalences of these three anelloviruses increased with the number of months
      after birth of the individual and reached 100% for individuals at one year of
      age. Dual or triple infection of TTV, TTMDV, and/or TTMV was seen in 10 (47.6%)
      of 21 infants 9 to 180 days of age and more frequently among infants 181 to 364
      days of age (20/23 [86.9%]), comparable with the 93.1% (243/261) prevalence among
      subjects 1 to 81 years of age, indicating early acquisition of dual or triple
      anellovirus infection during infancy.

PMID- 18094128
TI  - Brain abscess caused by Streptomyces infection following penetration trauma: case
      report and results of susceptibility analysis of 92 isolates of Streptomyces
      species submitted to the CDC from 2000 to 2004.
AB  - The case of a patient who presented with a brain abscess caused by Streptomyces
      infection following penetrating cerebral trauma with a soil-contaminated object
      generated an interest in optimizing antimicrobial therapy. Collaboration with the
      Centers for Disease Control and Prevention led to the analysis of susceptibility
      data for Streptomyces isolates that suggested that amikacin (100% susceptibility
      for 92 isolates tested) and linezolid, an oxazolidinone (100% susceptibility for
      41 isolates tested), offer reliable activity against all isolates.

PMID- 18094129
TI  - Selection of a surrogate agent (fluconazole or voriconazole) for initial
      susceptibility testing of posaconazole against Candida spp.: results from a
      global antifungal surveillance program.
AB  - There are currently no FDA-approved broth microdilution antifungal susceptibility
      testing products or interpretive breakpoints for susceptibility testing of the
      new triazole posaconazole. Fluconazole and voriconazole are in the same triazole
      class as posaconazole, have CLSI-approved interpretive MIC breakpoints, and are
      available on some commercially available MIC panels. We investigated whether one
      or both of these agents may be useful as a surrogate marker for posaconazole
      susceptibility. Fluconazole, voriconazole, and posaconazole MIC results for
      10,807 isolates of Candida spp. were analyzed to validate a potential surrogate
      marker for posaconazole activity against indicated species. For illustrative
      purposes, we applied the voriconazole MIC breakpoints to posaconazole
      (susceptible, < or =1 microg/ml; susceptible dose dependent, 2 microg/ml;
      resistant, > or =4 microg/ml) and compared these MIC results and categorical
      interpretations with those of fluconazole and voriconazole by using regression
      statistics and categorical agreement. For all 10,807 isolates, the absolute
      categorical agreement was 91.1% (0.1% very major errors [VME], 1.2% major errors
      [ME], and 7.6% minor errors [M]) using fluconazole as the surrogate marker and
      97.7% (0.3% VME 0.1% ME, and 1.9% M) using voriconazole as the surrogate. The
      results with fluconazole improved to a categorical agreement of 93.7% (0.1% VME,
      0.2% ME, and 6.0% M) when results for Candida krusei (not indicated for
      fluconazole testing) were omitted. Either fluconazole or voriconazole MIC results
      may serve as surrogate markers to predict the susceptibility of Candida spp. to
      posaconazole.

PMID- 18094130
TI  - Evaluation of commercial antisera for Salmonella serotyping.
AB  - We compared a set of commercial Salmonella somatic and flagellar serotyping
      antisera to in-house-prepared antisera from the Microbial Diseases Laboratory,
      California Department of Public Health, using 327 Salmonella enterica strains
      belonging to subgroups I, II, IIIa, IIIb, and IV. The sensitivities of Denka
      Seiken (Tokyo, Japan) somatic and flagellar antisera (using a tube agglutination
      assay) were 94.0% and 99.2%, respectively, and the specificity was 100% for both
      sets of sera. Polyvalent O and O1 antiserum sensitivity and specificity were
      >90%, with the exception of polyvalent O1 antiserum, for which sensitivity was
      88.9%. When Denka Seiken flagellar antisera were used in a slide agglutination
      assay, the sensitivity and accuracy dropped to 88.9% and the specificity fell to
      91%. Overall, Denka Seiken commercial antisera performed very well and, together
      with the comprehensive range of factors available, offer laboratories quality
      reagents suitable for serotyping strains of salmonellae.

PMID- 18094131
TI  - Isolation and characterization of Bartonella bacilliformis from an expatriate
      Ecuadorian.
AB  - Carrion's disease is typically biphasic with acute febrile illness characterized
      by bacteremia and severe hemolytic anemia (Oroya fever), followed by benign,
      chronic cutaneous lesions (verruga peruana). The causative agent, Bartonella
      bacilliformis, is endemic in specific regions of Peru and Ecuador. We describe
      atypical infection in an expatriate patient who presented with acute splenomegaly
      and anemia 3 years after visiting Ecuador. Initial serology and PCR of the
      patient's blood and serum were negative for Bartonella henselae, Bartonella
      quintana, and B. bacilliformis. Histology of splenic biopsy was suggestive of
      bacillary angiomatosis, but immunohistochemistry ruled out B. henselae and B.
      quintana. Bacilli (isolate EC-01) were subsequently cultured from the patient's
      blood and analyzed using multilocus sequence typing, protein gel electrophoresis
      with Western blotting, and an immunofluorescence assay (IFA) against a panel of
      sera from patients with Oroya fever in Peru. The EC-01 nucleotide sequences (gltA
      and internal transcribed spacer) and protein band banding pattern were most
      similar to a subset of B. bacilliformis isolates from the region of Caraz,
      Ancash, in Peru, where B. bacilliformis is endemic. By IFA, the patient's serum
      reacted strongly to two out of the three Peruvian B. bacilliformis isolates
      tested, and EC-01 antigen reacted with 13/20 Oroya fever sera. Bacilliary
      angiomatosis-like lesions were also detected in the spleen of the patient, who
      was inapparently infected with B. bacilliformis and who presumably acquired
      infection in a region of Ecuador where B. bacilliformis was not thought to be
      endemic. This study suggests that the range of B. bacilliformis may be expanding
      from areas of endemicity in Ecuador and that infection may present as atypical
      clinical disease.

PMID- 18094132
TI  - Single-nucleotide polymorphism in two representative multidrug-resistant
      Mycobacterium bovis isolates collected from patients in a Spanish hospital
      harboring a human infection outbreak.

PMID- 18094133
TI  - Colorimetric detection of multidrug-resistant or extensively drug-resistant
      tuberculosis by use of malachite green indicator dye.
AB  - The malachite green microtube (MGMT) susceptibility assay was performed directly
      on sputum specimens (n = 80) and indirectly on Mycobacterium tuberculosis
      clinical isolates (n = 60). The technique is based on the malachite green dye,
      which changes color in response to M. tuberculosis growth. The MGMT assay is
      simple and rapid and does not require expensive instruments.

PMID- 18094134
TI  - Molecular method for Bartonella species identification in clinical and
      environmental samples.
AB  - A new, efficient molecular method for detection of Bartonella, based on the 16S
      23S rRNA intergenic spacer and 16S rRNA amplification by multiplex PCR combined
      with reverse line blotting, was designed. This assay could simultaneously detect
      20 different known species and other Bartonella species not described previously.

PMID- 18094135
TI  - Dual-reporter phenotypic assay for human immunodeficiency viruses.
AB  - We have established a novel human immunodeficiency virus (HIV) tandem-reporter
      assay using HIV receptor-transduced NP-2 cells with long terminal repeat
      controlled beta-galactosidase, inserted internal ribosome entry site, and
      secretary alkaline phosphatase genes. This assay allows users to detect
      replication of clinical isolates, indicating its useful application as an HIV
      phenotypic assay.

PMID- 18094136
TI  - Utility of real-time PCR for diagnosis of Legionnaires' disease in routine
      clinical practice.
AB  - The main aim of our study was to determine the added value of PCR for the
      diagnosis of Legionnaires' disease (LD) in routine clinical practice. The
      specimens were samples submitted for routine diagnosis of pneumonia from December
      2002 to November 2005. Patients were evaluated if, in addition to PCR, the
      results of at least one of the following diagnostic tests were available: (i)
      culture for Legionella spp. on buffered charcoal yeast extract agar or (ii)
      detection of Legionella pneumophila antigen in urine specimens. Of the 151
      evaluated patients, 37 (25%) fulfilled the European Working Group on Legionella
      Infections criteria for a confirmed case of LD (the "gold standard"). An
      estimated sensitivity, specificity, and overall percent agreement of 86% (32 of
      37; 95% confidence interval [CI] = 72 to 95%), 95% (107 of 112; 95% CI = 90 to
      98%), and 93% (139 of 149), respectively, were found for 16S rRNA-based PCR, and
      corresponding values of 92% (34 of 37; 95% CI = 78 to 98%), 98% (110 of 112; 95%
      CI = 93 to 100%), and 97% (144 of 149), respectively, were found for the mip gene
      based PCR. A total of 35 patients were diagnosed by using the urinary antigen
      test, and 34 were diagnosed by the 16S rRNA-based PCR. With the mip gene PCR one
      more case of LD (n = 36; not significant) was detected. By combining urinary
      antigen test and the mip gene PCR, LD was diagnosed in an additional 4 (11%)
      patients versus the use of the urinary antigen test alone. The addition of a L.
      pneumophila-specific mip gene PCR to a urinary antigen test is useful in patients
      with suspected LD who produce sputum and might allow the early detection of a
      significant number of additional patients.

PMID- 18094137
TI  - Multiplex PCR that can distinguish between immunologically cross- reactive
      serovar 3, 6, and 8 Actinobacillus pleuropneumoniae strains.
AB  - We describe a highly sensitive and specific multiplex PCR, based on capsular loci
      and the species specific apxIV gene, that unequivocally differentiates serovar 3,
      6, and 8 Actinobacillus pleuropneumoniae strains that are cross-reactive in
      conventional immunological tests.

PMID- 18094138
TI  - Rapid detection and molecular serotyping of adenovirus by use of PCR followed by
      electrospray ionization mass spectrometry.
AB  - We have developed a PCR/electrospray ionization mass spectrometry (PCR/ESI-MS)
      assay for the rapid detection, identification, and serotyping of human
      adenoviruses. The assay employs a high-performance mass spectrometer to "weigh"
      the amplicons obtained from PCR using primers designed to amplify known human
      adenoviruses. Masses are converted to base compositions and, by comparison
      against a database of the genetic sequences, the serotype present in a sample is
      determined. The performance of the assay was demonstrated with quantified viral
      standards and environmental and human clinical samples collected from a military
      training facility. Over 500 samples per day can be analyzed with sensitivities
      greater than 100 genomes per reaction. This approach can be applied to many other
      families of infectious agents for rapid and sensitive analysis.

PMID- 18094139
TI  - Molecular epidemiology of extended-spectrum beta-lactamases among Escherichia
      coli isolates collected in a Swedish hospital and its associated health care
      facilities from 2001 to 2006.
AB  - The genetic characteristics and molecular epidemiology of extended-spectrum beta
      lactamases (ESBLs) among Escherichia coli isolates were investigated at a general
      hospital and its associated health care facilities in Stockholm, Sweden, during
      the period from 2001 to 2006. Of 87 consecutive nonduplicate ESBL-positive
      isolates, 80 isolates encoded CTX-M-type ESBLs, 64 of which were group 1 enzymes.
      TEM-type and OXA-type beta-lactamases were encoded in 63 and 59% of the ESBL
      isolates, respectively. Pulsed-field gel electrophoresis (PFGE) analysis revealed
      40 different pulsotypes, consisting of 11 clones accounting for 66% of all
      isolates, and 29 unique patterns. Moreover, of the 11 clones, clones 1 and 4
      comprised half of the clonally related isolates (28 of 57). Clone 1 was a
      persistent endemic clone in the area throughout the years, and clone 4 emerged in
      2003. However, in recent years, clone 1 isolates were no longer predominant and
      were gradually replaced by new emerging strains. Concerning beta-lactamase gene
      profiles in relation to PFGE pulsotypes, clone-related bla profiles were observed
      in certain clones, while in most cases different bla profiles could be observed
      in the same clone, and the same bla profile could be present in different clones.
      The molecular epidemiology of ESBL-positive E. coli in the area shows shifts in
      predominant strains and increased clonal diversity over time. The study also
      indicated that both clonal spread of epidemic strains and transfer of
      transposable genetic elements might contribute to the proliferation of ESBLs.

PMID- 18094140
TI  - Early impairment of gut function and gut flora supporting a role for alteration
      of gastrointestinal mucosa in human immunodeficiency virus pathogenesis.
AB  - Our results show that impairment of the gastrointestinal tracts in human
      immunodeficiency virus (HIV)-positive patients is present in the early phases of
      HIV disease. This impairment is associated with alterations in gut microbiota and
      intestinal inflammatory parameters. These findings support the hypothesis that
      alterations at the gastrointestinal-tract level are a key factor in HIV
      pathogenesis.

PMID- 18094141
TI  - Multiplex detection of human herpesviruses from archival specimens by using
      matrix-assisted laser desorption ionization-time of flight mass spectrometry.
AB  - The human herpesviruses are involved in a variety of diseases. Large-scale
      evaluation of the clinical and epidemiological importance of different
      herpesviruses requires high-throughput methods. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a method
      that has a multiplex capacity enabling simultaneous detection of several viruses
      in a single sample. PCR-based methods for the multiplex detection of all known
      human herpesviruses were developed on the MALDI-TOF MS system. A variety of 882
      archival samples, including bronchoalveolar lavage, conjunctival fluid, sore
      secretion, blister material, plasma, serum, and urine, analyzed for herpesviruses
      using PCR-based reference methods, were used to evaluate the MALDI-TOF MS method.
      The overall concordance rate between the MALDI-TOF MS method and the reference
      methods was 95.6% (kappa = 0.90). In summary, the MALDI-TOF MS method is well
      suited for large-scale detection of all known human herpesviruses in a wide
      variety of archival biological specimens.

PMID- 18094142
TI  - Defective trafficking and localization of mutated transferrin receptor 2:
      implications for type 3 hereditary hemochromatosis.
AB  - Transferrin receptor 2 (TfR2), a homologue of transferrin receptor 1 (TfR1), is a
      key molecule involved in the regulation of iron homeostasis. Mutations in TfR2
      result in iron overload with similar features to HFE-associated hereditary
      hemochromatosis. The precise role of TfR2 in iron metabolism and the functional
      consequences of disease-causing mutations have not been fully determined. We have
      expressed wild-type and various mutant forms of TfR2 that are associated with
      human disease in a mouse liver cell line. Intracellular and surface analysis
      shows that all the TfR2 mutations analyzed cause the intracellular retention of
      the protein in the endoplasmic reticulum, whereas the wild-type protein is
      expressed in endocytic structures and at the cell surface. Our results indicate
      that the majority of mutations that cause type 3 hereditary hemochromatosis are a
      consequence of the defective localization of the protein.

PMID- 18094143
TI  - Transport model of the human Na+-coupled L-ascorbic acid (vitamin C) transporter
      SVCT1.
AB  - Vitamin C (L-ascorbic acid) is an essential micronutrient that serves as an
      antioxidant and as a cofactor in many enzymatic reactions. Intestinal absorption
      and renal reabsorption of the vitamin is mediated by the epithelial apical L
      ascorbic acid cotransporter SVCT1 (SLC23A1). We explored the molecular mechanisms
      of SVCT1-mediated L-ascorbic acid transport using radiotracer and voltage-clamp
      techniques in RNA-injected Xenopus oocytes. L-ascorbic acid transport was
      saturable (K(0.5) approximately 70 microM), temperature dependent (Q(10)
      approximately 5), and energized by the Na(+) electrochemical potential gradient.
      We obtained a Na(+)-L-ascorbic acid coupling ratio of 2:1 from simultaneous
      measurement of currents and fluxes. L-ascorbic acid and Na(+) saturation kinetics
      as a function of cosubstrate concentrations revealed a simultaneous transport
      mechanism in which binding is ordered Na(+), L-ascorbic acid, Na(+). In the
      absence of L-ascorbic acid, SVCT1 mediated pre-steady-state currents that decayed
      with time constants 3-15 ms. Transients were described by single Boltzmann
      distributions. At 100 mM Na(+), maximal charge translocation (Q(max)) was
      approximately 25 nC, around a midpoint (V(0.5)) at -9 mV, and with apparent
      valence approximately -1. Q(max) was conserved upon progressive removal of Na(+),
      whereas V(0.5) shifted to more hyperpolarized potentials. Model simulation
      predicted that the pre-steady-state current predominantly results from an ion
      well effect on binding of the first Na(+) partway within the membrane electric
      field. We present a transport model for SVCT1 that will provide a framework for
      investigating the impact of specific mutations and polymorphisms in SLC23A1 and
      help us better understand the contribution of SVCT1 to vitamin C metabolism in
      health and disease.

PMID- 18094144
TI  - Ontogeny of Ca2+-induced Ca2+ release in rabbit ventricular myocytes.
AB  - It is commonly accepted that L-type Ca(2+) channel-mediated Ca(2+)-induced Ca(2+)
      release (CICR) is the dominant mode of excitation-contraction (E-C) coupling in
      the adult mammalian heart and that there is no appreciable CICR in neonates.
      However, we have observed that cell contraction in the neonatal heart was
      significantly decreased after sarcoplasmic reticulum (SR) Ca(2+) depletion with
      caffeine. Therefore, the present study investigated the developmental changes of
      CICR in rabbit ventricular myocytes at 3, 10, 20, and 56 days of age. We found
      that the inhibitory effect of the L-type Ca(2+) current (I(Ca)) inhibitor
      nifedipine (Nif; 15 microM) caused an increasingly larger reduction of Ca(2+)
      transients on depolarization in older age groups [from approximately 15% in 3-day
      old (3d) myocytes to approximately 90% in 56-day-old (56d) myocytes]. The
      remaining Ca(2+) transient in the presence of Nif in younger age groups was
      eliminated by the inhibition of Na(+)/Ca(2+) exchanger (NCX) with the subsequent
      addition of 10 microM KB-R7943 (KB-R). Furthermore, Ca(2+) transients were
      significantly reduced in magnitude after the depletion of SR Ca(2+) with caffeine
      in all age groups, although the effect was significantly greater in the older age
      groups (from approximately 40% in 3d myocytes up to approximately 70% in 56d
      myocytes). This SR Ca(2+)-sensitive Ca(2+) transient in the earliest
      developmental stage was insensitive to Nif but was sensitive to the subsequent
      addition of KB-R, indicating the presence of NCX-mediated CICR that decreased
      significantly with age (from approximately 37% in 3d myocytes to approximately
      0.5% in 56d myocytes). In contrast, the I(Ca)-mediated CICR increased
      significantly with age (from approximately 10% in 3d myocytes to approximately
      70% in 56d myocytes). The CICR gain as estimated by the integral of the CICR
      Ca(2+) transient divided by the integral of its Ca(2+) transient trigger was
      smaller when mediated by NCX ( approximately 1.0 for 3d myocytes) than when
      mediated by I(Ca) ( approximately 3.0 for 56d myocytes). We conclude that the
      lower-efficiency NCX-mediated CICR is a predominant mode of CICR in the earliest
      developmental stages that gradually decreases as the more efficient L-type Ca(2+)
      channel-mediated CICR increases in prominence with ontogeny.

PMID- 18094145
TI  - Targeting of the molecular chaperone oxygen-regulated protein 150 (ORP150) to
      mitochondria and its induction by cellular stress.
AB  - Oxygen-regulated protein 150 (ORP150) is an inducible endoplasmic reticulum (ER)
      chaperone molecule that is upregulated after numerous cellular insults and has a
      cytoprotective role in renal, neural, and cardiac models of ischemia-reperfusion
      injury. ORP150 also has been shown to play a role in cellular Ca(2+) homeostasis,
      and in turn, regulating calpain activity. In this study, we identified ORP150 in
      whole rat renal cortical mitochondria and matrix fractions, demonstrated the
      targeting of an ORP150-GFP construct to the mitochondria of NIH-3T3 cells, and
      showed that the NH(2)-terminal 13 amino acids of ORP150 are sufficient for this
      translocation. ORP150 expression was found to be regulated by the anti-C/enhancer
      binding protein homologous protein (CHOP)/GADD153 transcription factor and ORP150
      levels increased in the mitochondria and ER of COS-7 cells after diverse
      stresses, including hypoxia, serum starvation, prolyl hydroxylase inhibition with
      dimethyloxaloylglycine, and exposure to tunicamycin, ethidium, bromide, and 2
      deoxyglucose. Induction of the mitochondrial specific stress response in COS-7
      cells through expression of an ornithine transcarbamylase mutant (Delta OTC)
      increased mitochondrial ORP150 levels and mitochondrial calpain activity. To
      determine whether mitochondrial ORP150 and mitochondrial calpain 10 interact, rat
      cortical mitochondria exposed to Ca(2+) resulted in ORP150 cleavage in a calpain
      inhibitor-dependent manner, revealing that ORP150 is a substrate and may be
      regulated by calpain 10. These data reveal a novel cellular localization for
      ORP150 and that mitochondrial ORP150 is upregulated by CHOP/GADD153 in response
      to mitochondrial and ER stress. Our data also reveal that ORP150 is a substrate
      for mitochondrial calpain 10.

PMID- 18094146
TI  - Modulation of the Kir7.1 potassium channel by extracellular and intracellular pH.
AB  - Inwardly rectifying K(+) (K(ir)) channels in the apical membrane of the retinal
      pigment epithelium (RPE) contribute to extracellular K(+) homeostasis in the
      distal retina by mediating K(+) secretion. Multiple lines of evidence suggest
      that these channels are composed of Kir7.1. Previously, we showed that native
      K(ir) channels in bovine RPE are modulated by changes in intracellular pH in the
      physiological range. In the present study, we used the Xenopus laevis oocyte
      expression system to investigate the pH dependence of cloned human Kir7.1
      channels and several point mutants involving histidine residues in the NH(2) and
      COOH termini. Kir7.1 channels were inhibited by strong extracellular
      acidification and modulated by intracellular pH in a biphasic manner, with
      maximal activity at about intracellular pH (pH(i)) 7.0 and inhibition by
      acidification or alkalinization. Replacement of histidine 26 (H26) in the NH(2)
      terminus with alanine eliminated the requirement of protons for channel activity
      and increased sensitivity to proton-induced inhibition, resulting in maximal
      channel activity at alkaline pH(i) and smaller whole cell currents at resting
      pH(i) compared with wild-type Kir7.1. When H26 was replaced with arginine, the
      pH(i) sensitivity profile was similar to that of the H26A mutant but with the
      pK(a) shifted to a more acidic value, giving rise to whole cell current amplitude
      at resting pH(i) that was comparable to that of wild-type Kir7.1. These results
      indicate that Kir7.1 channels are modulated by intracellular protons by diverse
      mechanisms and suggest that H26 is important for channel activation at
      physiological pH(i) and that it influences an unidentified proton-induced
      inhibitory mechanism.

PMID- 18094147
TI  - Spontaneous myogenic differentiation of Flk-1-positive cells from adult pancreas
      and other nonmuscle tissues.
AB  - At the embryonic or fetal stages, autonomously myogenic cells (AMCs), i.e., cells
      able to spontaneously differentiate into skeletal myotubes, have been identified
      from several different sites other than skeletal muscle, including the vascular
      compartment. However, in the adult animal, AMCs from skeletal muscle-devoid
      tissues have been described in only two cases. One is represented by thymic myoid
      cells, a restricted population of committed myogenic progenitors of unknown
      derivation present in the thymic medulla; the other is represented by a small
      subset of adipose tissue-associated cells, which we recently identified. In the
      present study we report, for the first time, the presence of spontaneously
      differentiating myogenic precursors in the pancreas and in other skeletal muscle
      devoid organs such as spleen and stomach, as well as in the periaortic tissue of
      adult mice. Immunomagnetic selection procedures indicate that AMCs derive from
      Flk-1(+) progenitors. Individual clones of myogenic cells from nonmuscle organs
      are morphologically and functionally indistinguishable from skeletal muscle
      derived primary myoblasts. Moreover, they can be induced to proliferate in vitro
      and are able to participate in muscle regeneration in vivo. Thus, we provide
      evidence that fully competent myogenic progenitors can be derived from the Flk
      1(+) compartment of several adult tissues that are embryologically unrelated to
      skeletal muscle.

PMID- 18094148
TI  - Uterine artery myosin phosphatase isoform switching and increased sensitivity to
      SNP in a rat L-NAME model of hypertension of pregnancy.
AB  - Dramatic and vascular bed-specific hemodynamic changes occur in pregnancy and
      hypertension of pregnancy (HtP). Because myosin phosphatase (MP) is the primary
      effector of smooth muscle relaxation and a key target of signaling pathways that
      regulate vascular tone, we hypothesized that MP expression would be altered in
      these conditions. The abundance of the targeting/regulatory subunit of MP (MYPT1)
      mRNA and protein was increased 1.7- to 2.0-fold specifically in the uterine
      arteries (UAs) of late-pregnant rats without isoform switching. In a model of HtP
      in which nitric oxide (NO) synthesis is blocked by the chronic administration of
      N(omega)-nitro-L-arginine methyl ester, MYPT1 was downregulated and switched to
      the splice variant isoform that codes for the COOH-terminal leucine zipper motif.
      This was associated with increased sensitivity of the main UA and its subbranches
      to the vasorelaxant effects of the NO donor drug sodium nitroprusside. This
      difference was abolished by pretreatment with the phosphatase inhibitor
      tautomycetin. The sensitivity of relaxation to the NO second messenger cGMP was
      also increased under calcium-clamp conditions in permeabilized UAs, indicating
      heightened activation of MP. The changes in MP expression in HtP were largely
      prevented by treatment with the antihypertensive medicine hydralazine. We propose
      that MYPT1 isoform switching is an adaptive response to reduce vascular
      resistance and maintain uterine blood flow in the setting of hypertension
      triggered inward remodeling of the UAs in hypertension of pregnancy.

PMID- 18094149
TI  - Na+/H+ exchange and pH regulation in the control of neutrophil chemokinesis and
      chemotaxis.
AB  - Large proton fluxes accompany cell migration, but their precise role remains
      unclear. We studied pH regulation during the course of chemokinesis and
      chemotaxis in human neutrophils stimulated by attractant peptides. Activation of
      cell motility by chemoattractants was accompanied by a marked increase in
      metabolic acid generation, attributable to energy consumption by the contractile
      machinery and to stimulation of the NADPH oxidase and the ancillary hexose
      monophosphate shunt. Despite the increase in acid production, the cytosol
      underwent a sizable alkalinization, caused by acceleration of Na(+)/H(+)
      exchange. The development of the alkalinization mirrored the increase in the rate
      of cell migration, suggesting a causal relationship. However, elimination of
      Na(+)/H(+) exchange by omission of external Na(+) or by addition of potent
      inhibitors was without effect on either chemokinesis or chemotaxis, provided the
      cytosolic pH remained near neutrality. At more acidic levels, cell motility was
      progressively inhibited. These observations suggest that Na(+)/H(+) exchange
      plays a permissive role in cell motility but is not required for the initiation
      or development of the migratory response. Chemokinesis also was found to be
      exquisitely sensitive to extracellular acidification. This property may account
      for the inability of neutrophils to access abscesses and solid tumors that have
      been reported to have inordinately low pH.

PMID- 18094150
TI  - The DNase of gammaherpesviruses impairs recognition by virus-specific CD8+ T
      cells through an additional host shutoff function.
AB  - The DNase/alkaline exonuclease (AE) genes are well conserved in all herpesvirus
      families, but recent studies have shown that the AE proteins of
      gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma
      associated herpesvirus (KSHV) exhibit an additional function which shuts down
      host protein synthesis. One correlate of this additional shutoff function is that
      levels of cell surface HLA molecules are downregulated, raising the possibility
      that shutoff/AE genes of gammaherpesviruses might contribute to viral immune
      evasion. In this study, we show that both BGLF5 (EBV) and SOX (KSHV) shutoff/AE
      proteins do indeed impair the ability of virus-specific CD8+ T-cell clones to
      recognize endogenous antigen via HLA class I. Random mutagenesis of the BGLF5
      gene enabled us to genetically separate the shutoff and AE functions and to
      demonstrate that the shutoff function was the critical factor determining whether
      BGLF5 mutants can impair T-cell recognition. These data provide further evidence
      that EBV has multiple mechanisms to modulate HLA class I-restricted T-cell
      responses, thus enabling the virus to replicate and persist in the immune
      competent host.

PMID- 18094151
TI  - Structures of two coronavirus main proteases: implications for substrate binding
      and antiviral drug design.
AB  - Coronaviruses (CoVs) can infect humans and multiple species of animals, causing a
      wide spectrum of diseases. The coronavirus main protease (M(pro)), which plays a
      pivotal role in viral gene expression and replication through the proteolytic
      processing of replicase polyproteins, is an attractive target for anti-CoV drug
      design. In this study, the crystal structures of infectious bronchitis virus
      (IBV) M(pro) and a severe acute respiratory syndrome CoV (SARS-CoV) M(pro) mutant
      (H41A), in complex with an N-terminal autocleavage substrate, were individually
      determined to elucidate the structural flexibility and substrate binding of
      M(pro). A monomeric form of IBV M(pro) was identified for the first time in CoV
      M(pro) structures. A comparison of these two structures to other available M(pro)
      structures provides new insights for the design of substrate-based inhibitors
      targeting CoV M(pro)s. Furthermore, a Michael acceptor inhibitor (named N3) was
      cocrystallized with IBV M(pro) and was found to demonstrate in vitro inactivation
      of IBV M(pro) and potent antiviral activity against IBV in chicken embryos. This
      provides a feasible animal model for designing wide-spectrum inhibitors against
      CoV-associated diseases. The structure-based optimization of N3 has yielded two
      more efficacious lead compounds, N27 and H16, with potent inhibition against SARS
      CoV M(pro).

PMID- 18094152
TI  - Definition of the minimal cis-acting sequences necessary for genome maturation of
      the herpesvirus murine cytomegalovirus.
AB  - Herpesvirus DNA replication proceeds via concatemeric replicative intermediates
      that are comprised of head-to-tail-linked genomes. Genome maturation is carried
      out by the terminase, a protein complex that mediates both insertion of
      concatemer DNA into capsids and its subsequent cleavage to release genomes within
      these capsids. This cleavage is sequence specific, but the governing cis-acting
      DNA sequences are only partially characterized. Two highly conserved motifs
      called pac1 and pac2 lie near the ends of herpesvirus genomes and are known to be
      critical for genome maturation. However, the potential importance of other
      sequences has not been fully investigated. We have undertaken to define all of
      the sequences necessary for efficient genome maturation for a herpesvirus by
      inserting ectopic cleavage sites into the murine cytomegalovirus genome and
      assessing their ability to mediate genome maturation. A combination of deletion
      and substitution mutations revealed that the minimal cleavage site is large (
      approximately 180 bp) and complex. Sequences distal of pac1 (relative to the
      point of cleavage) were dispensable, suggesting that pac1 may be the sole cis
      acting element on this side of the cleavage site. In contrast, a region distal to
      pac2 up to 150 bp from the point of cleavage was essential. Scanning
      substitutions revealed that the pac2 side of the cleavage site is complex and may
      contain multiple cis-acting sequence elements in addition to pac2. These results
      should facilitate the identification of trans-acting factors that bind to these
      elements and the elucidation of their functions. Such information will be
      critical for understanding the molecular basis of this complex process.

PMID- 18094153
TI  - The spike protein of infectious bronchitis virus is retained intracellularly by a
      tyrosine motif.
AB  - We have analyzed the intracellular transport of the spike (S) protein of
      infectious bronchitis virus (IBV), an avian coronavirus. Surface expression was
      analyzed by immunofluorescence microscopy, by surface biotinylation, and by
      syncytium formation by S-expressing cells. By applying these methods, the S
      protein was found to be retained intracellularly. Tyr1143 in the cytoplasmic tail
      was shown to be a crucial component of the retention signal. Deletion of a
      dilysine motif that has previously been suggested to function as a retrieval
      signal did not abolish intracellular retention. Treatment of the S proteins with
      endoglycosidases did not reveal any differences between the parental and the
      mutant proteins. Furthermore, all S proteins analyzed were posttranslationally
      cleaved into the subunits S1 and S2. In coexpression experiments, the S protein
      was found to colocalize with a Golgi marker. Taken together, these results
      indicate that the S protein of IBV is retained at a late Golgi compartment.
      Therefore, this viral surface protein differs from the S proteins of
      transmissible gastroenteritis virus and severe acute respiratory syndrome
      coronavirus, which are retained at a pre-Golgi compartment or transported to the
      cell surface, respectively. The implications of these differences are discussed.

PMID- 18094154
TI  - Visualization of double-stranded RNA in cells supporting hepatitis C virus RNA
      replication.
AB  - The mechanisms involved in hepatitis C virus (HCV) RNA replication are unknown,
      and this aspect of the virus life cycle is not understood. It is thought that
      virus-encoded nonstructural proteins and RNA genomes interact on rearranged
      endoplasmic reticulum (ER) membranes to form replication complexes, which are
      believed to be sites of RNA synthesis. We report that, through the use of an
      antibody specific for double-stranded RNA (dsRNA), dsRNA is readily detectable in
      Huh-7 cells that contain replicating HCV JFH-1 genomes but is absent in control
      cells. Therefore, as that of other RNA virus genomes, the replication of the HCV
      genome may involve the generation of a dsRNA replicative intermediate. In Huh-7
      cells supporting HCV RNA replication, dsRNA was observed as discrete foci,
      associated with virus-encoded NS5A and core proteins and identical in morphology
      and distribution to structures containing HCV RNA visualized by fluorescence
      based hybridization methods. Three-dimensional reconstruction of deconvolved z
      stack images of virus-infected cells provided detailed insight into the
      relationship among dsRNA foci, NS5A, the ER, and lipid droplets (LDs). This
      analysis revealed that dsRNA foci were located on the surface of the ER and often
      surrounded, partially or wholly, by a network of ER-bound NS5A protein.
      Additionally, virus-induced dsRNA foci were juxtaposed to LDs, attached to the
      ER. Thus, we report the visualization of HCV-induced dsRNA foci, the likely sites
      of virus RNA replication, and propose that HCV genome synthesis occurs at LD
      associated sites attached to the ER in virus-infected cells.

PMID- 18094155
TI  - 4E10-resistant variants in a human immunodeficiency virus type 1 subtype C
      infected individual with an anti-membrane-proximal external region-neutralizing
      antibody response.
AB  - The broadly neutralizing monoclonal antibody (MAb) 4E10 recognizes a linear
      epitope in the C terminus of the membrane-proximal external region (MPER) of
      gp41. This epitope is particularly attractive for vaccine design because it is
      highly conserved among human immunodeficiency virus type 1 (HIV-1) strains and
      neutralization escape in vivo has not been observed. Multiple env genes were
      cloned from an HIV-1 subtype C virus isolated from a 7-year-old perinatally
      infected child who had anti-MPER neutralizing antibodies. One clone (TM20.13) was
      resistant to 4E10 neutralization as a result of an F673L substitution in the
      MPER. Frequency analysis showed that F673L was present in 33% of the viral
      variants and in all cases was linked to the presence of an intact 2F5 epitope.
      Two other envelope clones were sensitive to 4E10 neutralization, but TM20.5 was
      10-fold less sensitive than TM20.6. Substitutions at positions 674 and 677 within
      the MPER rendered TM20.5 more sensitive to 4E10 but had no effect on TM20.6.
      Using chimeric and mutant constructs of these two variants, we further
      demonstrated that the lentivirus lytic peptide-2 domain in the cytoplasmic tail
      affected the accessibility of the 4E10 epitope, as well as virus infectivity.
      Collectively, these genetic changes in the face of a neutralizing antibody
      response to the MPER strongly suggested immune escape from antibody responses
      targeting this region.

PMID- 18094156
TI  - Conserved leucines in N-terminal heptad repeat HR1 of envelope fusion protein F
      of group II nucleopolyhedroviruses are important for correct processing and
      essential for fusogenicity.
AB  - The heptad repeat (HR), a conserved structural motif of class I viral fusion
      proteins, is responsible for the formation of a six-helix bundle structure during
      the envelope fusion process. The insect baculovirus F protein is a newly found
      budded virus envelope fusion protein which possesses common features to class I
      fusion proteins, such as proteolytic cleavage and the presence of an N-terminal
      open fusion peptide and multiple HR domains on the transmembrane subunit F(1).
      Similar to many vertebrate viral fusion proteins, a conserved leucine zipper
      motif is predicted in this HR region proximal to the fusion peptide in
      baculovirus F proteins. To facilitate our understanding of the functional role of
      this leucine zipper-like HR1 domain in baculovirus F protein synthesis,
      processing, and viral infectivity, key leucine residues (Leu209, Leu216, and
      Leu223) were replaced by alanine (A) or arginine (R), respectively. By using
      Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) as a pseudotype
      expression system, we demonstrated that all mutant F proteins incorporated into
      budded virus, indicating that leucine substitutions did not affect intercellular
      trafficking of F. Furin-like protease cleavage was not affected by any of the
      leucine substitutions; however, the disulfide bridging and N-linked glycosylation
      patterns were partly altered. Single substitutions in HR1 showed that the three
      leucine residues were critical for F fusogenicity and the rescue of AcMNPV
      infectivity. Our results support the view that the leucine zipper-like HR1 domain
      is important to safeguard the proper folding, glycosylation, and fusogenicity of
      baculovirus F proteins.

PMID- 18094157
TI  - Evidence for differential roles for NKG2D receptor signaling in innate host
      defense against coronavirus-induced neurological and liver disease.
AB  - Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis
      virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10
      (CXCL10) resulted in increased survival and reduced viral burden within the brain
      and liver compared to those of mice infected with an isogenic control virus
      (MHV), supporting an important role for CXCL10 in innate immune responses
      following viral infection. Enhanced protection in MHV-CXCL10-infected mice
      correlated with increased gamma interferon (IFN-gamma) production by infiltrating
      natural killer (NK) cells within the brain and reduced liver pathology. To
      explore the underlying mechanisms associated with protection from disease in MHV
      CXCL10-infected mice, the functional contributions of the NK cell-activating
      receptor NKG2D in host defense were examined. The administration of an NKG2D
      blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN
      gamma production in the brain, or affect liver pathology. However, NKG2D
      neutralization increased viral titers within the liver, suggesting a protective
      role for NKG2D signaling in this organ. These data indicate that (i) CXCL10
      enhances innate immune responses, resulting in protection from MHV-induced
      neurological and liver disease; (ii) elevated NK cell IFN-gamma expression in the
      brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D
      signaling promotes antiviral activity within the livers of MHV-infected mice that
      is not dependent on IFN-gamma and tumor necrosis factor alpha secretion.

PMID- 18094158
TI  - Interaction between the human immunodeficiency virus type 1 Gag matrix domain and
      phosphatidylinositol-(4,5)-bisphosphate is essential for efficient gag membrane
      binding.
AB  - Human immunodeficiency virus type 1 (HIV-1) particle assembly mediated by the
      viral structural protein Gag occurs predominantly on the plasma membrane (PM).
      Although it is known that the matrix (MA) domain of Gag plays a major role in PM
      localization, molecular mechanisms that determine the location of assembly remain
      to be elucidated. We observed previously that overexpression of
      polyphosphoinositide 5-phosphatase IV (5ptaseIV) that depletes PM
      phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)] impairs virus particle
      production and redirects processed Gag to intracellular compartments. In this
      study, we examined the impact of PI(4,5)P(2) depletion on the subcellular
      localization of the entire Gag population using Gag-fluorescent protein chimeras.
      Upon 5ptaseIV overexpression, in addition to perinuclear localization, Gag also
      showed a hazy cytosolic signal, suggesting that PI(4,5)P(2) depletion impairs Gag
      membrane binding. Indeed, Gag was less membrane bound in PI(4,5)P(2)-depleted
      cells, as assessed by biochemical analysis. These observations are consistent
      with the hypothesis that Gag interacts with PI(4,5)P(2). To examine a putative
      Gag interaction with PI(4,5)P(2), we developed an in vitro binding assay using
      full-length myristoylated Gag and liposome-associated PI(4,5)P(2). Using this
      assay, we observed that PI(4,5)P(2) significantly enhances liposome binding of
      wild-type Gag. In contrast, a Gag derivative lacking MA did not require
      PI(4,5)P(2) for efficient liposome binding. To analyze the involvement of MA in
      PI(4,5)P(2) binding further, we examined MA basic amino acid substitution
      mutants. These mutants, previously shown to localize in perinuclear compartments,
      bound PI(4,5)P(2)-containing liposomes weakly. Altogether, these results indicate
      that HIV-1 Gag binds PI(4,5)P(2) on the membrane and that the MA basic domain
      mediates this interaction.

PMID- 18094159
TI  - Vaccination of macaques with adjuvanted formalin-inactivated influenza A virus
      (H5N1) vaccines: protection against H5N1 challenge without disease enhancement.
AB  - We investigated the ability of adjuvanted, inactivated split-virion influenza A
      virus (H5N1) vaccines to protect against infection and demonstrated that the
      disease exacerbation phenomenon seen with adjuvanted formaldehyde-inactivated
      respiratory syncytial virus and measles virus investigational vaccines did not
      occur with these H5N1 vaccines. Macaques were vaccinated twice with or without an
      aluminum hydroxide or oil-in-water emulsion adjuvanted vaccine. Three months
      later, animals were challenged with homologous wild-type H5N1. No signs of
      vaccine-induced disease exacerbation were seen. With either adjuvant, vaccination
      induced functional and cross-reactive antibodies and protected the lungs and
      upper respiratory tract. Without an adjuvant, the vaccine provided partial
      protection. Best results were obtained with the emulsion adjuvant.

PMID- 18094160
TI  - Human immunodeficiency virus type 1 Vpr inhibits axonal outgrowth through
      induction of mitochondrial dysfunction.
AB  - Human immunodeficiency virus type 1 (HIV-1)-infected macrophages damage mature
      neurons in the brain, although their effect on neuronal development has not been
      clarified. In this study, we show that HIV-1-infected macrophages produce factors
      that impair the development of neuronal precursor cells and that soluble viral
      protein R (Vpr) is one of the factors that has the ability to suppress axonal
      growth. Cell biological analysis revealed that extracellularly administered
      recombinant Vpr (rVpr) clearly accumulated in mitochondria where a Vpr-binding
      protein adenine nucleotide translocator localizes and also decreased the
      mitochondrial membrane potential, which led to ATP synthesis. The depletion of
      ATP synthesis reduced the transportation of mitochondria within neurites. This
      mitochondrial dysfunction inhibited axonal growth even when the frequency of
      apoptosis was not significant. We also found that point mutations of arginine (R)
      residues to alanine (A) residues at positions 73, 77, and 80 rendered rVpr
      incapable of causing mitochondrial membrane depolarization and axonal growth
      inhibition. Moreover, the Vpr-induced inhibition was suppressed after treatment
      with a ubiquinone analogue (ubiquinone-10). Our results suggest that soluble Vpr
      is a major viral factor that causes a disturbance in neuronal development through
      the induction of mitochondrial dysfunction. Since ubiquinone-10 protects the
      neuronal plasticity in vitro, it may be a therapeutic agent that can offer
      defense against HIV-1-associated neurological disease.

PMID- 18094161
TI  - CCR5Delta32 59537-G/A promoter polymorphism is associated with low translational
      efficiency and the loss of CCR5Delta32 protective effects.
AB  - We have recently demonstrated that the CCR5Delta32 protein interacts with CCR5
      and CXCR4 and down-modulates their cell surface expression. We have also reported
      the absence of detectable expression of the truncated CCR5Delta32 protein in four
      out of six human immunodeficiency virus-infected (HIV(+)) CCR5(-/-) individuals.
      To explain the defect in protein expression in these samples, we cloned and
      sequenced the promoter regions of the six HIV(+) individuals. We have identified
      several polymorphisms in the CCR5Delta32 promoter region, but these polymorphisms
      were not associated with significant differences in mRNA levels. Coupled in vitro
      transcription/translation and polyribosome analysis demonstrated a strong
      association between a variant genotype designated CCR5Delta32 59537-A/A and a low
      translation efficiency. Protein analysis indicated that the peripheral blood
      mononuclear cells from two of the HIV(+) CCR5(-/-) individuals carrying the
      CCR5Delta32 59537-A/A variant expressed trace amounts of CCR5Delta32 protein
      compared to the individuals carrying the CCR5Delta32 59537-G/G genotype. The
      results imply that the absence of CCR5Delta32 protein in two HIV(+) individuals
      is due to a genetic defect in the translation of the protein. Together, these
      results highlight the importance of the CCR5Delta32 protein as an HIV suppressive
      factor and provide further insight into the mechanism of the protective effect of
      the CCR5Delta32 mutation.

PMID- 18094163
TI  - Probing the structural states of human immunodeficiency virus type 1 pr55gag by
      using monoclonal antibodies.
AB  - Gag-FP (fluorescent protein) fusion constructs are commonly used to study human
      immunodeficiency virus type 1 assembly, yielding diffuse signals throughout the
      cytoplasm along with punctate signals routinely described as virus-like particles
      (VLPs) representing assembled but unprocessed Gag. However, these particles
      cannot be accurately described as VLPs, since fluorescence microscopy cannot
      provide structural resolution. We demonstrate here that the inability of a
      monoclonal p24 antibody to bind its cognate epitope when unprocessed Gag is
      assembled distinguishes VLPs from unassembled, monomeric Gag. Furthermore, we
      show that assembled and unassembled Gag punctate signals travel along
      microtubules. These monoclonal antibody studies provide a new tool for examining
      retroviral assembly.

PMID- 18094162
TI  - Binding of ICP4, TATA-binding protein, and RNA polymerase II to herpes simplex
      virus type 1 immediate-early, early, and late promoters in virus-infected cells.
AB  - The binding of herpes simplex virus type 1 ICP4, TATA-binding protein (TBP), and
      RNA polymerase II (polII) to the promoter regions of representative immediate
      early (IE) (ICP0), early (E) (thymidine kinase [tk]), and late (L) (glycoprotein
      C [gC]) genes on the viral genome was examined as a function of time
      postinfection, viral DNA replication, cis-acting sites for TFIID in the tk and gC
      promoters, and genetic background of ICP4. The binding of TBP and polII to the IE
      ICP0 promoter was independent of the presence of ICP4, whereas the binding of TBP
      and polII to the tk and gC promoters occurred only when ICP4 also bound to the
      promoters, suggesting that the presence of ICP4 at the promoters of E and L genes
      in virus-infected cells is crucial for the formation of transcription complexes
      on these promoters. When the TATA box of the tk promoter or the initiator element
      (INR) of the gC promoter was mutated, a reduction in the amount of TBP and polII
      binding was observed. However, a reduction in the amount of ICP4 binding to the
      promoters was also observed, suggesting that the binding of TBP-containing
      complexes and ICP4 is cooperative. The binding of ICP4, TBP, and polII was also
      observed on the gC promoter at early times postinfection or when DNA synthesis
      was inhibited, suggesting that transcription complexes may be formed early on L
      promoters and that additional events or proteins are required for expression. The
      ability to form these early complexes on the gC promoter required the DNA-binding
      domain but in addition required the carboxyl-terminal 524 amino acids of ICP4,
      which is missing the virus n208. This region was not required to form TBP- and
      polII-containing complexes on the tk promoter. n208 activates E but not L genes
      during viral infection. These data suggest that a region of ICP4 may
      differentiate between forming TBP- and polII-containing complexes on E and L
      promoters.

PMID- 18094164
TI  - Jaagsiekte sheep retrovirus utilizes a pH-dependent endocytosis pathway for
      entry.
AB  - Using Moloney murine leukemia virus pseudovirions bearing the envelope protein of
      Jaagsiekte sheep retrovirus (JSRV), we report here that entry was weakly
      inhibited by lysosomotropic agents but was profoundly blocked by bafilomycin A1
      (BafA1). Kinetics studies revealed that JSRV entry is a slow process and was
      substantially blocked by a dominant-negative mutant of dynamin. Interestingly, a
      low-pH pulse overcame the BafA1 block to JSRV infection, although this occurred
      only if virus-bound cells were preincubated at 37 degrees C, consistent with a
      very early entry event such as endocytosis being required before the low-pH
      dependent step occurs. Moreover, JSRV pseudovirions were resistant to low-pH
      inactivation. Altogether, this study reveals that JSRV utilizes a pH-dependent,
      dynamin-associated endocytosis pathway for entry that differs from the classical
      pH-dependent entry pathway of vesicular stomatitis virus.

PMID- 18094165
TI  - Fusogenicity of Jaagsiekte sheep retrovirus envelope protein is dependent on low
      pH and is enhanced by cytoplasmic tail truncations.
AB  - Jaagsiekte sheep retrovirus (JSRV) envelope (Env) is an active oncogene
      responsible for neoplastic transformation in animals and cultured cells. In this
      study, we used syncytium induction and fluorescence-based cell fusion assays to
      investigate JSRV Env fusion and its modulation by the cytoplasmic tail (CT). We
      found that JSRV Env induced syncytia in cells overexpressing the receptor for
      JSRV and that a low pH was required for this process to occur. Fusion kinetics
      studies revealed that cell-cell fusion by JSRV Env at neutral pH was poor, taking
      up to a day, in sharp contrast to fusion at low pH, which peaked within 2 min
      following a low-pH trigger. Deletion of the C-terminal 7 or 16 amino acids of the
      JSRV Env CT had no or little effect on fusion, yet additional truncation toward
      the membrane-spanning domain, resulting in mutants retaining as little as 1 amino
      acid of the CT, led to progressively increased syncytium formation at neutral pH
      that was further enhanced by low-pH treatment. Notably, the severely truncated
      mutants showed elevated levels of surface subunits in culture medium, suggesting
      that the CT truncations resulted in conformational changes in the ectodomain of
      Env that impaired surface subunit associations. Taken together, this study
      reveals for the first time that the fusion activity of the JSRV Env protein is
      dependent on a low pH and is modulated by the CT, whose truncation overcomes, at
      least partially, the low-pH requirement for fusion and enhances Env fusion
      activity and kinetics.

PMID- 18094166
TI  - Molecular characterization of feline immunodeficiency virus budding.
AB  - Infection of domestic cats with feline immunodeficiency virus (FIV) is an
      important model system for studying human immunodeficiency virus type 1 (HIV-1)
      infection due to numerous similarities in pathogenesis induced by these two
      lentiviruses. However, many molecular aspects of FIV replication remain poorly
      understood. It is well established that retroviruses use short peptide motifs in
      Gag, known as late domains, to usurp cellular endosomal sorting machinery and
      promote virus release from infected cells. For example, the Pro-Thr/Ser-Ala-Pro
      [P(T/S)AP] motif of HIV-1 Gag interacts directly with Tsg101, a component of the
      endosomal sorting complex required for transport I (ESCRT-I). A Tyr-Pro-Asp-Leu
      (YPDL) motif in equine infectious anemia virus (EIAV), and a related sequence in
      HIV-1, bind the endosomal sorting factor Alix. In this study we sought to
      identify and characterize FIV late domain(s) and elucidate cellular machinery
      involved in FIV release. We determined that mutagenesis of a PSAP motif in FIV
      Gag, small interfering RNA-mediated knockdown of Tsg101 expression, and
      overexpression of a P(T/S)AP-binding fragment of Tsg101 (TSG-5') each inhibited
      FIV release. We also observed direct binding of FIV Gag peptides to Tsg101. In
      contrast, mutagenesis of a potential Alix-binding motif in FIV Gag did not affect
      FIV release. Similarly, expression of the HIV-1/EIAV Gag-binding domain of Alix
      (Alix-V) did not disrupt FIV budding, and FIV Gag peptides showed no affinity for
      Alix-V. Our data demonstrate that FIV relies predominantly on a Tsg101-binding
      PSAP motif in the C terminus of Gag to promote virus release in HeLa cells, and
      this budding mechanism is highly conserved in feline cells.

PMID- 18094167
TI  - Human immunodeficiency virus type 1 Nef recruits the guanine exchange factor Vav1
      via an unexpected interface into plasma membrane microdomains for association
      with p21-activated kinase 2 activity.
AB  - Alterations of T-cell receptor signaling by human immunodeficiency virus type 1
      (HIV-1) Nef involve its association with a highly active subpopulation of p21
      activated kinase 2 (PAK2) within a dynamic signalosome assembled in detergent
      insoluble membrane microdomains. Nef-PAK2 complexes contain the GTPases Rac and
      Cdc42 as well as a factor providing guanine nucleotide exchange factor (GEF)
      activity for Rac/Cdc42. However, the identity of this GEF has remained
      controversial. Previous studies suggested the association of Nef with at least
      three independent GEFs, Vav, DOCK2/ELMO1, and betaPix. Here we used a broad panel
      of approaches to address which of these GEFs is involved in the functional
      interaction of Nef with PAK2 activity. Biochemical fractionation and confocal
      microscopy revealed that Nef recruits Vav1, but not DOCK2/ELMO1 or betaPix, to
      membrane microdomains. Transient RNAi knockdown, analysis of cell lines defective
      for expression of Vav1 or DOCK2 as well as use of a betaPix binding-deficient
      PAK2 variant confirmed a role for Vav1 but not DOCK2 or betaPix in Nef's
      association with PAK2 activity. Nef-mediated microdomain recruitment of Vav1
      occurred independently of the Src homology 3 domain binding PxxP motif, which is
      known to connect Nef to many cellular signaling processes. Instead, a recently
      described protein interaction surface surrounding Nef residue F195 was identified
      as critical for Nef-mediated raft recruitment of Vav1. These results identify
      Vav1 as a relevant component of the Nef-PAK2 signalosome and provide a molecular
      basis for the role of F195 in formation of a catalytically active Nef-PAK2
      complex.

PMID- 18094168
TI  - Dominant-negative FADD rescues the in vivo fitness of a cytomegalovirus lacking
      an antiapoptotic viral gene.
AB  - Genes that inhibit apoptosis have been described for many DNA viruses.
      Herpesviruses often contain even more than one gene to control cell death.
      Apoptosis inhibition by viral genes is postulated to contribute to viral fitness,
      although a formal proof is pending. To address this question, we studied the
      mouse cytomegalovirus (MCMV) protein M36, which binds to caspase-8 and blocks
      death receptor-induced apoptosis. The growth of MCMV recombinants lacking M36
      (DeltaM36) was attenuated in vitro and in vivo. In vitro, caspase inhibition by
      zVAD-fmk blocked apoptosis in DeltaM36-infected macrophages and rescued the
      growth of the mutant. In vivo, DeltaM36 infection foci in liver tissue contained
      significantly more apoptotic hepatocytes and Kupffer cells than did revertant
      virus foci, and apoptosis occurred during the early phase of virus replication
      prior to virion assembly. To further delineate the mode of M36 function, we
      replaced the M36 gene with a dominant-negative FADD (FADD(DN)) in an MCMV
      recombinant. FADD(DN) was expressed in cells infected with the recombinant and
      blocked the death-receptor pathway, replacing the antiapoptotic function of M36.
      Most importantly, FADD(DN) rescued DeltaM36 virus replication, both in vitro and
      in vivo. These findings have identified the biological role of M36 and define
      apoptosis inhibition as a key determinant of viral fitness.

PMID- 18094169
TI  - Stabilization of TM trimer interactions during activation of moloney murine
      leukemia virus Env.
AB  - The transmembrane subunit (TM) of the trimeric retrovirus Env complex is thought
      to direct virus-cell membrane fusion by refolding into a cell membrane
      interacting, extended form that subsequently folds back on itself into a very
      stable trimer of hairpin-like TM polypeptides. However, so far there is only
      limited evidence for the formation of a stable TM trimer during Env activation.
      Here we have studied the oligomer composition and stability of an intermediate
      and the fully activated form of Moloney murine leukemia virus (Mo-MLV) Env.
      Activation of Mo-MLV Env is controlled by isomerization of its intersubunit
      disulfide. This results in surface subunit (SU) dissociation and TM refolding. If
      activation is done in the presence of an alkylator, this will modify the
      isomerization-active thiol in the SU of Env and arrest Env at an intermediate
      stage, the isomerization-arrested state (IAS) of its activation pathway. We
      generated IAS and fully activated Envs in vitro and in vivo and studied their
      states of oligomerization by two-dimensional blue native polyacrylamide gel
      electrophoresis (PAGE) and nonreducing sodium dodecyl sulfate (SDS)-PAGE. The IAS
      Env was composed of trimers of SU-TM complexes, whereas the activated Env
      consisted of SU monomers and TM trimers. When the oligomers were subjected to
      mild SDS treatment the TM trimer was found to be 3.5 times more resistant than
      the IAS oligomer. Thus, this demonstrates that a structural conversion of TM
      takes place during activation, which results in the formation of a stable TM
      trimer.

PMID- 18094170
TI  - R-Peptide cleavage potentiates fusion-controlling isomerization of the
      intersubunit disulfide in Moloney murine leukemia virus Env.
AB  - Fusion of the membrane of the Moloney murine leukemia virus (Mo-MLV) Env protein
      is facilitated by cleavage of the R peptide from the cytoplasmic tail of its TM
      subunit, but the mechanism for this effect has remained obscure. The fusion is
      also controlled by the isomerization of the intersubunit disulfide of the Env SU
      TM complex. In the present study, we used several R-peptide-cleavage-inhibited
      virus mutants to show that the R peptide suppresses the isomerization reaction in
      both in vitro and in vivo assays. Thus, the R peptide affects early steps in the
      activation pathway of murine leukemia virus Env.

PMID- 18094171
TI  - CD4 T cells contribute to virus control and pathology following central nervous
      system infection with neurotropic mouse hepatitis virus.
AB  - Replication of the neurotropic mouse hepatitis virus strain JHM (JHMV) is
      controlled primarily by CD8(+) T-cell effectors utilizing gamma interferon (IFN
      gamma) and perforin-mediated cytotoxicity. CD4(+) T cells provide an auxiliary
      function(s) for CD8(+) T-cell survival; however, their direct contribution to
      control of virus replication and pathology is unclear. To examine a direct role
      of CD4(+) T cells in viral clearance and pathology, pathogenesis was compared in
      mice deficient in both perforin and IFN-gamma that were selectively reconstituted
      for these functions via transfer of virus-specific memory CD4(+) T cells. CD4(+)
      T cells from immunized wild-type, perforin-deficient, and IFN-gamma-deficient
      donors all initially reduced virus replication. However, prolonged viral control
      by IFN-gamma-competent donors suggested that IFN-gamma is important for sustained
      virus control. Local release of IFN-gamma was evident by up-regulation of class
      II molecules on microglia in recipients of IFN-gamma producing CD4(+) T cells.
      CD4(+) T-cell-mediated antiviral activity correlated with diminished clinical
      symptoms, pathology, and demyelination. Both wild-type donor CD90.1 and recipient
      CD90.2 CD4(+) T cells trafficked into the central nervous system (CNS) parenchyma
      and localized to infected white matter, correlating with decreased numbers of
      virus-infected oligodendrocytes in the CNS. These data support a direct, if
      limited, antiviral role for CD4(+) T cells early during acute JHMV
      encephalomyelitis. Although the antiviral effector mechanism is initially
      independent of IFN-gamma secretion, sustained control of CNS virus replication by
      CD4(+) T cells requires IFN-gamma.

PMID- 18094172
TI  - Pseudodiploid genome organization AIDS full-length human immunodeficiency virus
      type 1 DNA synthesis.
AB  - Template switching between copackaged human immunodeficiency virus type 1 (HIV-1)
      genomic RNAs is genetically silent when identical RNAs are copackaged but yields
      recombinants when virions contain two distinct RNAs. Sequencing has revealed that
      errors at retroviral recombination junctions are infrequent, suggesting that
      template switching is not intrinsically mutagenic. Here, we tested the hypothesis
      that template switching may instead contribute to replication fidelity. This
      hypothesis predicts that reverse transcription of a single-copy gene will be more
      error prone than replication in the presence of a second copy. To test this, HIV
      1-based vectors containing both lacZ and the puromycin resistance marker were
      expressed either alone or with an excess of an "empty" vector lacking lacZ and
      puro. This resulted in virions with either RNA homodimers or haploid genomes with
      only a single lacZ-puro RNA. In untreated cells, lacZ inactivation rates
      suggested that haploid vector reverse transcription was slightly more error prone
      than that of homodimerized pseudodiploid vectors. Haploid reverse transcription
      was at least threefold more error prone than pseudodiploid-templated synthesis
      when slowed by hydroxyurea treatment or stopped prematurely with zidovudine.
      Individual products of one- and two-copy genes revealed both nucleotide
      substitutions and deletions, with deletions more frequent than point mutations
      among haploid genome products. Similar spectra of defective products were
      observed at early reverse transcription time points and among products of haploid
      virions. These results indicate that faithful, full-length reverse transcription
      products were underrepresented in the absence of a reserve of genetic information
      and suggest that template switching contributes to HIV-1 genomic integrity.

PMID- 18094174
TI  - Relative influence of the adeno-associated virus (AAV) type 2 p5 element for
      recombinant AAV vector site-specific integration.
AB  - The p5 promoter region of the adeno-associated virus type 2 (AAV-2) rep gene has
      been described as essential for Rep-mediated site-specific integration (RMSSI) of
      plasmid sequences in human chromosome 19. We report here that insertion of a full
      length or minimal p5 element between the viral inverted terminal repeats does not
      significantly increase RMSSI of a recombinant AAV (rAAV) vector after infection
      of growth-arrested or proliferating human cells. This result suggests that the p5
      element may not improve RMSSI of rAAV vectors in vivo.

PMID- 18094173
TI  - The glycoprotein and the matrix protein of rabies virus affect pathogenicity by
      regulating viral replication and facilitating cell-to-cell spread.
AB  - While the glycoprotein (G) of rabies virus (RV) is known to play a predominant
      role in the pathogenesis of rabies, the function of the RV matrix protein (M) in
      RV pathogenicity is not completely clear. To further investigate the roles of
      these proteins in viral pathogenicity, we constructed chimeric recombinant
      viruses by exchanging the G and M genes of the attenuated SN strain with those of
      the highly pathogenic SB strain. Infection of mice with these chimeric viruses
      revealed a significant increase in the pathogenicity of the SN strain bearing the
      RV G from the pathogenic SB strain. Moreover, the pathogenicity was further
      increased when both G and M from SB were introduced into SN. Interestingly, the
      replacement of the G or M gene or both in SN by the corresponding genes of SB was
      associated with a significant decrease in the rate of viral replication and viral
      RNA synthesis. In addition, a chimeric SN virus bearing both the M and G genes
      from SB exhibited more efficient cell-to-cell spread than a chimeric SN virus in
      which only the G gene was replaced. Together, these data indicate that both G and
      M play an important role in RV pathogenesis by regulating virus replication and
      facilitating cell-to-cell spread.

PMID- 18094175
TI  - The programmed death-1 and interleukin-10 pathways play a down-modulatory role in
      LP-BM5 retrovirus-induced murine immunodeficiency syndrome.
AB  - Pathology due to the immune system's response to viral infections often
      represents a delicate balance between inhibition of viral pathogenesis and
      regulation of protective immunity. In susceptible C57BL/6 (B6) mice, the murine
      retroviral isolate LP-BM5 induces splenomegaly, hypergammaglobulinemia, profound
      B- and T-cell immunodeficiency, and increased susceptibility to opportunistic
      pathogens and terminal B-cell lymphomas. Here, we report that B6.PD-1 (programmed
      death-1) and B6.IL-10 knockout mice are substantially more susceptible to LP-BM5
      induced disease than wild-type B6 mice. LP-BM5-infected B6.PD-1(-/-) mice
      developed more severe splenomegaly, hypergammaglobulinemia, and immunodeficiency
      than infected B6 mice: PD-1(-/-) mice are more susceptible to lower doses of LP
      BM5 and show more exaggerated disease early postinfection. LP-BM5-infected B6.IL
      10(-/-) mice also develop exaggerated LP-BM5-induced disease, compared to B6
      mice, without a significant change in the retroviral load. By reciprocal
      reconstitution experiments, comparing wild-type versus PD-1(-/-) sources of the
      requisite cells for LP-BM5 pathogenesis-CD4 T and B cells, PD-1(+) B cells appear
      to be crucial in the normal limitation of LP-BM5-induced disease in B6 mice.
      Also, infected B6 mice have increased CD11b(+) spleen cells that express
      interleukin-10 (IL-10). However, PD-1(-/-) mice, though showing an even greater
      expansion of CD11b(+) cells after LP-BM5 inoculation, did not show an equivalent
      increase in IL-10-producing cells. Thus, it appears that PD-1/PD-L interactions
      and IL-10 are primarily important in moderating the effects of LP-BM5-induced
      disease in B6 mice.

PMID- 18094176
TI  - Direct correlation between sialic acid binding and infection of cells by two
      human polyomaviruses (JC virus and BK virus).
AB  - For the human polyomaviruses JC virus (JCV) and BK virus (BKV), the first step to
      a successful infection involves binding to sialic acid moieties located on the
      surfaces of host cells. By stripping and then reconstituting specific sialic acid
      linkages on host cells, we show that JCV uses both alpha(2,3)-linked and
      alpha(2,6)-linked sialic acids on N-linked glycoproteins to infect cells. For
      both JCV and BKV, the sialic acid linkages required for cell surface binding
      directly correlate with the linkages required for infection. In addition to
      sialic acid linkage data, these data suggest that the third sugar from the
      carbohydrate chain terminus is important for virus binding and infection.

PMID- 18094178
TI  - Functional genetic analysis of rhesus cytomegalovirus: Rh01 is an epithelial cell
      tropism factor.
AB  - Rhesus cytomegalovirus (RhCMV) is an emerging model for human cytomegalovirus
      (HCMV) pathogenesis that facilitates experimental CMV infection of a natural
      primate host closely related to humans. We have generated a library of RhCMV
      mutants with lesions in genes whose HCMV orthologues have been characterized as
      nonessential for replication in human fibroblasts, and we characterized their
      replication in rhesus fibroblasts and epithelial cells. The RhCMV mutants grew
      well in fibroblasts, as predicted by earlier studies with HCMV. However,
      mutations in four genes caused replication defects in rhesus retinal pigment
      epithelial cells: Rh01 (an HCMV TRL1 orthologue), Rh159 (HCMV UL148), Rh160 (HCMV
      UL132), and Rh203 (HCMV US22). Growth of the Rh01-deficient mutant was examined
      in detail. After entry into epithelial cells, the mutant expressed representative
      viral proteins, accumulated viral DNA, and generated infectious virus, but it
      failed to spread efficiently. We conclude that Rh01 is a cell tropism determinant
      that has the potential to dramatically affect virus spread and pathogenesis.

PMID- 18094177
TI  - Ty3 nucleocapsid controls localization of particle assembly.
AB  - Expression of the budding yeast retrotransposon Ty3 results in production of
      viruslike particles (VLPs) and retrotransposition. The Ty3 major structural
      protein, Gag3, similar to retrovirus Gag, is processed into capsid, spacer, and
      nucleocapsid (NC) during VLP maturation. The 57-amino-acid Ty3 NC protein has 17
      basic amino acids and contains one copy of the CX(2)CX(4)HX(4)C zinc-binding
      motif found in retrovirus NC proteins. Ty3 RNA, protein, and VLPs accumulate in
      clusters associated with RNA processing bodies (P bodies). This study
      investigated the role of the NC domain in Ty3-P body clustering and VLP assembly.
      Fifteen Ty3 NC Ala substitution and deletion mutants were examined using
      transposition, immunoblot, RNA protection, cDNA synthesis, and multimerization
      assays. Localization of Ty3 proteins and VLPs was characterized microscopically.
      Substitutions of each of the conserved residues of the zinc-binding motif
      resulted in the loss of Ty3 RNA packaging. Substitution of the first two of four
      conserved residues in this motif caused the loss of Ty3 RNA and protein
      clustering with P bodies and disrupted particle formation. NC was shown to be a
      mediator of formation of Ty3 RNA foci and association of Ty3 RNA and protein with
      P bodies. Mutations that disrupted these NC functions resulted in various degrees
      of Gag3 nuclear localization and a spectrum of different particle states. Our
      findings are consistent with the model that Ty3 assembly is associated with P
      body components. We hypothesize that the NC domain acts as a molecular switch to
      control Gag3 conformational states that affect both assembly and localization.

PMID- 18094179
TI  - Hepatitis B surface antigen levels and sequences of natural hepatitis B virus
      variants influence the assembly and secretion of hepatitis d virus.
AB  - Various domains of hepatitis B surface antigen (HBsAg) are essential for the
      assembly and secretion of hepatitis D virus (HDV). This study investigated the
      influences of the levels and sequences of HBsAg of naturally occurring HBV
      variants on the assembly and secretion of HDV. Six hepatitis B virus (HBV)
      producing plasmids (three genotype B and three genotype C) and six HBsAg
      expression plasmids that expressed various HBsAg levels were constructed from the
      sera of HDV-infected patients. These plasmids were cotransfected with six
      expression plasmids of HDV of genotype 1, 2, or 4 into the Huh-7 hepatoma cell
      line. Serum HBsAg and HBV DNA levels were correlated with HDV RNA levels and
      outcomes of chronic hepatitis D (CHD) patients. The secretion of genotype 1, 2,
      or 4 HDV generally correlated with HBsAg levels but not with HBV genotypes or HBV
      DNA levels. Swapping and residue mutagenesis experiments of HBsAg-coding
      sequences revealed that the residue Pro-62 in the cytosolic domain-I affects the
      assembly and secretion of genotype 2 and 4 HDV and not those of genotype 1. The
      pre-S2 N-terminal deletion HBV mutant adversely affects secretion of the three
      HDV genotypes. In patients, serum HDV RNA levels correlated with HBsAg levels but
      not with HBV DNA levels. Viremia of HDV or HBV correlated with poor outcomes. In
      conclusion, the assembly and secretion of HDV were influenced by the amounts and
      sequences of HBsAg. For an effective treatment of CHD, reduction of HBsAg
      production in addition to the suppression of HBV and HDV replication might be
      crucial.

PMID- 18094180
TI  - Antibody-dependent enhancement of hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) often causes a persistent infection associated with
      hypergammaglobulinemia, high levels of antiviral antibody and circulating immune
      complexes, and immune complex disease. We previously reported that only a limited
      neutralizing activity to vesicular stomatitis virus or HCV pseudotype is
      generated in animals immunized with recombinant HCV envelope proteins and
      chronically infected HCV patient sera. Interestingly, when some of these
      neutralizing sera were diluted into a range of concentrations below those that
      reduced virus plaque number, an increase in pseudotype plaque formation was
      observed. Purified HCV E2-specific human monoclonal antibodies were used to
      further verify the specificity of this enhancement, and one- to twofold increases
      were apparent on permissive Huh-7 cells. The enhancement of HCV pseudotype titer
      could be inhibited by the addition of a Fc-specific anti-human immunoglobulin G
      Fab fragment to the virus-antibody mixture prior to infection. Treatment of cells
      with antibody to Fc receptor I (FcRI) or FcRII, but not FcRIII, also led to an
      inhibition of pseudotype titer enhancement in an additive manner. Human
      lymphoblastoid cell line (Raji), a poor host for HCV pseudotype infection,
      exhibited a four- to sixfold enhancement of pseudotype-mediated cell death upon
      incubation with antibody at nonneutralizing concentrations. A similar enhancement
      of cell culture-grown HCV infectivity by a human monoclonal antibody was also
      observed. Taken together, antibodies to viral epitopes enhancing HCV infection
      need to be taken into consideration for pathogenesis and in the development of an
      effective vaccine.

PMID- 18094181
TI  - Virus-specific T-cell immunity correlates with control of GB virus B infection in
      marmosets.
AB  - GB virus B (GBV-B) is a hepatotropic virus that is closely related to hepatitis C
      virus (HCV). GBV-B causes acute hepatitis in infected marmosets and tamarins and
      is therefore a useful small-animal model for the study of HCV. We investigated
      virus-specific T-cell responses in marmosets infected with GBV-B. Gamma
      interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay responses in the
      peripheral blood of two marmosets were assessed throughout the course of GBV-B
      infection. These T-cell responses were directed against the GBV-B nonstructural
      proteins 3 (NS3), 4A (NS4A), and 5B (NS5B), and their appearance was temporally
      associated with clearance of viremia. These marmosets were then rechallenged with
      GBV-B at least 3 months after clearance of the primary infection to determine if
      the animals were protected from reinfection. There was no detectable viremia
      following reinfection, although a sharp increase in T-cell responses against GBV
      B proteins was observed. Epitope mapping of T-cell responses to GBV-B was
      performed with liver and blood samples from both marmosets after rechallenge with
      GBV-B. Three shared, immunodominant T-cell epitopes within NS3 were identified in
      animals with multiple common major histocompatibility complex class I alleles.
      IFN-gamma ELISPOT responses were also detected in the livers of two marmosets
      that had resolved a primary GBV-B infection. These responses were high in
      frequency and were directed against epitopes within GBV-B NS3, NS4A, and NS5B
      proteins. These results indicate that virus-specific T-cell responses are
      detectable in the liver and blood of GBV-B-infected marmosets and that the
      clearance of GBV-B is associated with the appearance of these responses.

PMID- 18094182
TI  - Highly conserved regions of influenza a virus polymerase gene segments are
      critical for efficient viral RNA packaging.
AB  - The genome of the influenza A virus is composed of eight different segments of
      negative-sense RNA. These eight segments are incorporated into budding virions in
      an equimolar ratio through a mechanism that is not fully understood. Two
      different models have been proposed for packaging the viral ribonucleoproteins
      into newly assembling virus particles: the random-incorporation model and the
      selective-incorporation model. In the last few years, increasing evidence from
      many different laboratories that supports the selective-incorporation model has
      been accumulated. In particular, different groups have shown that some large
      viral RNA regions within the coding sequences at both the 5' and 3' ends of
      almost every segment are sufficient for packaging foreign RNA sequences. If the
      packaging regions are crucial for the viability of the virus, we would expect
      them to be conserved. Using large-scale analysis of influenza A virus sequences,
      we developed a method of identifying conserved RNA regions whose conservation
      cannot be explained by population structure or amino acid conservation.
      Interestingly, the conserved sequences are located within the regions identified
      as important for efficient packaging. By utilizing influenza virus reverse
      genetics, we have rescued mutant viruses containing synonymous mutations within
      these highly conserved regions. Packaging of viral RNAs in these viruses was
      analyzed by reverse transcription using a universal primer and quantitative PCR
      for individual segments. Employing this approach, we have identified regions in
      the polymerase gene segments that, if mutated, result in reductions of more than
      90% in the packaging of that particular polymerase viral RNA. Reductions in the
      level of packaging of a polymerase viral RNA frequently resulted in reductions of
      other viral RNAs as well, and the results form a pattern of hierarchy of segment
      interactions. This work provides further evidence for a selective packaging
      mechanism for influenza A viruses, demonstrating that these highly conserved
      regions are important for efficient packaging.

PMID- 18094183
TI  - The vaccinia virus B5 protein requires A34 for efficient intracellular
      trafficking from the endoplasmic reticulum to the site of wrapping and
      incorporation into progeny virions.
AB  - The glycoproteins encoded by the vaccinia virus A34R and B5R genes are involved
      in intracellular envelope virus formation and are highly conserved among
      orthopoxviruses. A recombinant virus that has the A34R gene deleted and the B5R
      gene replaced with a B5R gene fused to the enhanced green fluorescent protein
      (B5R-GFP) gene was created (vB5R-GFP/DeltaA34R) to investigate the role of A34
      during virion morphogenesis. Cells infected with vB5R-GFP/DeltaA34R displayed GFP
      fluorescence throughout the cytoplasm, which differed markedly from that seen in
      cells infected with a normal B5R-GFP-expressing virus (vB5R-GFP).
      Immunofluorescence and subcellular fractionation demonstrated that B5-GFP
      localizes with the endoplasmic reticulum in the absence of A34. Expression of
      either full-length A34 or a construct consisting of the lumenal and transmembrane
      domains restored normal trafficking of B5-GFP to the site of wrapping in the
      juxtanuclear region. Coimmunoprecipitation studies confirmed that B5 and A34
      interact through their luminal domains, and further analysis revealed that in the
      absence of A34, B5 is not efficiently incorporated into virions released from the
      cell.

PMID- 18094184
TI  - Structure of antibody-neutralized murine norovirus and unexpected differences
      from viruslike particles.
AB  - Noroviruses (family Caliciviridae) are the major cause of epidemic nonbacterial
      gastroenteritis in humans, but the mechanism of antibody neutralization is
      unknown and no structure of an infectious virion has been reported. Murine
      norovirus (MNV) is the only norovirus that can be grown in tissue culture,
      studied in an animal model, and reverse engineered via an infectious clone and to
      which neutralizing antibodies have been isolated. Presented here are the
      cryoelectron microscopy structures of an MNV virion and the virion in complex
      with neutralizing Fab fragments. The most striking differences between MNV and
      previous calicivirus structures are that the protruding domain is lifted off the
      shell domain by approximately 16A and rotated approximately 40 degrees in a
      clockwise fashion and forms new interactions at the P1 base that create a
      cagelike structure engulfing the shell domains. Neutralizing Fab fragments cover
      the outer surface of each copy of the capsid protein P2 domains without causing
      any apparent conformational changes. These unique features of MNV suggest that at
      least some caliciviruses undergo a capsid maturation process akin to that
      observed with other plant and bacterial viruses.

PMID- 18094185
TI  - Single intranasal immunization with recombinant adenovirus-based vaccine induces
      protective immunity against respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory
      tract disease in infancy and early childhood. Despite its importance as a
      pathogen, there is no licensed vaccine against RSV. The G glycoprotein of RSV, a
      major attachment protein, is a potentially important target for protective
      antiviral immune responses. Here, a recombinant replication-deficient adenovirus
      based vaccine, rAd/3xG, expressing the soluble core domain of G glycoprotein
      (amino acids 130 to 230) engineered by codon optimization and tandem repetition
      for higher-level expression, was constructed and evaluated for its potential as
      an RSV vaccine in a murine model. A single intranasal immunization with rAd/3xG
      provided potent protection against RSV challenge which lasted for more than 10
      weeks. Strong mucosal immunoglobulin A responses were also induced by a single
      intranasal immunization but not by intramuscular or oral administration of
      rAd/3xG. Interestingly, neither gamma interferon- nor interleukin-4-producing CD4
      T cells directed to I-E(d)-restricted epitope were detected in the lungs of
      rAd/3xG-immune mice upon challenge, whereas priming with vaccinia virus
      expressing RSV G (vvG) elicited strong Th1/Th2 mixed CD4 T-cell responses. Lung
      eosinophilia and vaccine-induced weight loss were significantly lower in the
      rAd/3xG-immune group than in the vvG-primed group. Together, our data demonstrate
      that a single intranasal administration of rAd/3xG elicits beneficial protective
      immunity and represents a promising vaccine regimen against RSV infection.

PMID- 18094186
TI  - Vaccinia virus A34 glycoprotein determines the protein composition of the
      extracellular virus envelope.
AB  - The outer envelope of the extracellular form of vaccinia virus contains five
      virus-encoded proteins, F13, A33, A34, A56, and B5, that, with the exception of
      A56, are implicated in virus egress or infectivity. A34, a type II transmembrane
      glycoprotein, is involved in the induction of actin tails, the release of
      enveloped virus from the surfaces of infected cells, and the disruption of the
      virus envelope after ligand binding prior to virus entry. To investigate
      interactions between A34 and other envelope proteins, a recombinant vaccinia
      virus (vA34R(HA)) expressing an epitope-tagged version of A34 (A34(HA)) was
      constructed by appending an epitope from influenza virus hemagglutinin to the C
      terminus of A34. Complexes of A34(HA) with B5 and A36, but not with A33 or F13,
      were detected in vA34R(HA)-infected cells. A series of vaccinia viruses
      expressing mutated versions of the B5 protein was used to investigate the
      domain(s) of B5 required for interaction with A34. Both the cytoplasmic and the
      transmembrane domains of B5 were dispensable for binding to A34. Most of the
      extracellular domain of B5, which contains four short consensus repeats
      homologous to complement control proteins, was sufficient for A34 interaction,
      indicating that both proteins interact through their ectodomains.
      Immunofluorescence experiments on cells infected with A34-deficient virus
      indicated that A34 is required for efficient targeting of B5, A36, and A33 into
      wrapped virions. Consistent with this observation, the envelope of A34-deficient
      virus contained normal amounts of F13 but decreased amounts of A33 and B5 with
      respect to the parental WR virus. These results point to A34 as a major
      determinant in the protein composition of the vaccinia virus envelope.

PMID- 18094187
TI  - Tobacco mosaic virus replicase-auxin/indole acetic acid protein interactions:
      reprogramming the auxin response pathway to enhance virus infection.
AB  - The replicase protein of Tobacco mosaic virus (TMV) disrupts the localization and
      stability of interacting auxin/indole acetic acid (Aux/IAA) proteins in
      Arabidopsis, altering auxin-mediated gene regulation and promoting disease
      development (M. S. Padmanabhan, S. P. Goregaoker, S. Golem, H. Shiferaw, and J.
      N. Culver, J. Virol. 79:2549-2558, 2005). In this study, a similar replicase
      Aux/IAA interaction affecting disease development was identified in tomato. The
      ability of the TMV replicase to interact with Aux/IAA proteins from diverse hosts
      suggests that these interactions contribute to the infection process. To examine
      the role of this interaction in virus pathogenicity, the replication and spread
      of a TMV mutant with a reduced ability to interact with specific Aux/IAA proteins
      were examined. Within young (4- to 6-week-old) leaf tissue, there were no
      significant differences in the abilities of Aux/IAA-interacting or 
      noninteracting viruses to replicate and spread. In contrast, in mature (10- to 12
      week-old) leaf tissue, the inability to interact with specific Aux/IAA proteins
      correlated with a significant reduction in virus accumulation. Correspondingly,
      interacting Aux/IAA levels are significantly higher in older tissue and the
      overaccumulation of a degradation-resistant Aux/IAA protein reduced virus
      accumulation in young leaf tissue. Combined, these findings suggest that TMV
      replicase-Aux/IAA interactions selectively enhance virus pathogenicity in tissues
      where Aux/IAA proteins accumulate. We speculate that the virus disrupts Aux/IAA
      functions as a means to reprogram the cellular environment of older cells to one
      that is more compatible for virus replication and spread.

PMID- 18094188
TI  - Mechanisms of zoonotic severe acute respiratory syndrome coronavirus host range
      expansion in human airway epithelium.
AB  - In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) emerged and
      caused over 8,000 human cases of infection and more than 700 deaths worldwide.
      Zoonotic SARS-CoV likely evolved to infect humans by a series of transmission
      events between humans and animals for sale in China. Using synthetic biology, we
      engineered the spike protein (S) from a civet strain, SZ16, into our epidemic
      strain infectious clone, creating the chimeric virus icSZ16-S, which was
      infectious but yielded progeny viruses incapable of propagating in vitro. After
      introducing a K479N mutation within the S receptor binding domain (RBD) of SZ16,
      the recombinant virus (icSZ16-S K479N) replicated in Vero cells but was severely
      debilitated in growth. The in vitro evolution of icSZ16-S K479N on human airway
      epithelial (HAE) cells produced two viruses (icSZ16-S K479N D8 and D22) with
      enhanced growth on HAE cells and on delayed brain tumor cells expressing the SARS
      CoV receptor, human angiotensin I converting enzyme 2 (hACE2). The icSZ16-S K479N
      D8 and D22 virus RBDs contained mutations in ACE2 contact residues, Y442F and
      L472F, that remodeled S interactions with hACE2. Further, these viruses were
      neutralized by a human monoclonal antibody (MAb), S230.15, but the parent icSZ16
      S K479N strain was eight times more resistant than the mutants. These data
      suggest that the human adaptation of zoonotic SARS-CoV strains may select for
      some variants that are highly susceptible to select MAbs that bind to RBDs. The
      epidemic, icSZ16-S K479N, and icSZ16-S K479N D22 viruses replicate similarly in
      the BALB/c mouse lung, highlighting the potential use of these zoonotic spike
      SARS-CoVs to assess vaccine or serotherapy efficacy in vivo.

PMID- 18094189
TI  - Transdominant inhibition of bovine viral diarrhea virus entry.
AB  - Bovine viral diarrhea virus (BVDV) is a positive-strand RNA virus and a member of
      the genus Pestivirus in the family Flaviviridae. To identify and characterize
      essential factors required for BVDV replication, a library expressing random
      fragments of the BVDV genome was screened for sequences that act as transdominant
      inhibitors of viral replication by conferring resistance to cytopathic BVDV
      induced cell death. We isolated a BVDV-nonpermissive MDBK cell clone that
      harbored a 1.2-kb insertion spanning the carboxy terminus of the envelope
      glycoprotein 1 (E1), the envelope glycoprotein E2, and the amino terminus of p7.
      Confirming the resistance phenotype conferred by this library clone, naive MDBK
      cells expressing this fragment were found to be 100- to 1,000-fold less
      permissive to both cytopathic and noncytopathic BVDV infection compared to
      parental MDBK cells, although these cells remained fully permissive to vesicular
      stomatitis virus. This restriction could be overcome by electroporation of BVDV
      RNA, indicating a block at one or more steps in viral entry prior to translation
      of the viral RNA. We determined that the E2 ectodomain was responsible for the
      inhibition to BVDV entry and that this block occurred downstream from BVDV
      interaction with the cellular receptor CD46 and virus binding, suggesting
      interference with a yet-unidentified BVDV entry factor.

PMID- 18094190
TI  - A single-amino-acid substitution in the TvbS1 receptor results in decreased
      susceptibility to infection by avian sarcoma and leukosis virus subgroups B and D
      and resistance to infection by subgroup E in vitro and in vivo.
AB  - The avian sarcoma and leukosis virus (ASLV) family of retroviruses contains five
      highly related envelope subgroups (A to E) thought to have evolved from a common
      viral ancestor in the chicken population. Three genetic loci in chickens
      determine the susceptibility or resistance of cells to infection by the subgroup
      A to E ASLVs. Some inbred lines of chickens display phenotypes that are somewhere
      in between either efficiently susceptible or resistant to infection by specific
      subgroups of ASLV. The tvb gene encodes the receptor for subgroups B, D, and E
      ASLVs. The wild-type Tvb(S1) receptor confers susceptibility to subgroups B, D,
      and E ASLVs. In this study, the genetic defect that accounts for the altered
      susceptibility of an inbred chicken line, line M, to infection by ASLV(B),
      ASLV(D), and ASLV(E) was identified. The tvb gene in line M, tvb(r2), encodes a
      mutant Tvb(S1) receptor protein with a substitution of a serine for a cysteine at
      position 125 (C125S). Here, we show that the C125S substitution in Tvb(S1)
      significantly reduces the susceptibility of line M cells to infection by ASLV(B)
      and ASLV(D) and virtually eliminates susceptibility to ASLV(E) infection both in
      cultured cells and in the incidence and growth of avian sarcoma virus-induced
      sarcomas in chickens. The C125S substitution significantly reduces the binding
      affinity of the Tvb(S1) receptor for the subgroup B, D, and E ASLV envelope
      glycoproteins. These are the first results that demonstrate a possible role of
      the cysteine-rich domain 3 in the function of the Tvb receptors.

PMID- 18094191
TI  - Inhibition of hepadnavirus reverse transcriptase-epsilon RNA interaction by
      porphyrin compounds.
AB  - The hepatitis B virus (HBV) reverse transcriptase (RT) plays a multitude of
      fundamental roles in the viral life cycle and is the key target in the
      development of anti-HBV chemotherapy. We report here that the endogenous small
      molecule iron protoporphyrin IX (hemin) and several related porphyrin compounds
      potently blocked a critical RT interaction with the viral RNA packaging
      signal/origin of replication, called epsilon. As RT-epsilon interaction is
      essential for the initiation of viral reverse transcription, which is primed by
      RT itself (protein priming), the porphyrin compounds dramatically suppressed the
      protein-priming reaction. Further studies demonstrated that these compounds could
      target the unique N-terminal domain of the RT protein, the so-called terminal
      protein. Hemin and related porphyrin compounds thus represent a novel class of
      agents that can block HBV RT functions through a mechanism and target that are
      completely distinct from those of existing anti-HBV drugs.

PMID- 18094192
TI  - Identification of cellular proteins that maintain retroviral epigenetic
      silencing: evidence for an antiviral response.
AB  - Integrated retroviral DNA is subject to epigenetic gene silencing, resulting in
      loss of expression of viral genes as well as reporter or therapeutic genes
      transduced by retroviral vectors. Possible mediators of such silencing include
      the histone deacetylase (HDAC) family of cellular proteins. We previously
      isolated HeLa cell populations that harbored silent avian sarcoma virus-based
      green fluorescent protein (GFP) vectors that could be reactivated by treatment
      with HDAC inhibitors. Here, we developed a small interfering RNA (siRNA)-based
      approach to identify specific host factors that participate in the maintenance of
      silencing. Knockdown of HDAC1, the transcriptional repressor Daxx (a binding
      partner of HDAC1), or heterochromatin protein 1 gamma resulted in robust and
      specific GFP reporter gene reactivation. Analyses of cell clones and diverse GFP
      vector constructs revealed that the roles of HDAC1 and Daxx in retroviral
      silencing are largely independent of the integration site or the promoter
      controlling the silent GFP reporter gene. Previous findings from our laboratory
      and those of others have suggested that Daxx and HDAC proteins may act broadly as
      part of an antiviral response to repress viral gene transcription. Expression of
      presumptive viral "countermeasure" proteins that are known to inhibit Daxx or
      HDACs (pp71, IE2, and Gam1) resulted in the reactivation of GFP reporter gene
      expression. This study has identified individual host factors that maintain
      retroviral silencing and supports the proposal that these factors participate in
      an antiviral response. Furthermore, our results indicate that siRNAs can be used
      as specific reagents to interrupt the maintenance of epigenetic silencing.

PMID- 18094193
TI  - Differential role of gamma interferon in inhibiting pulmonary eosinophilia and
      exacerbating systemic disease in fusion protein-immunized mice undergoing
      challenge infection with respiratory syncytial virus.
AB  - Secondary exposure to respiratory syncytial virus (RSV) can lead to
      immunopathology and enhanced disease in vaccinated individuals. Vaccination with
      individual RSV proteins influences the type of secondary RSV-specific immune
      response that develops upon challenge RSV infection, as well as the extent of
      immunopathology. RSV-specific memory CD4 T cells can directly contribute to
      immunopathology through their cytokine production. Immunization of BALB/c mice
      with a recombinant vaccinia virus (vv) expressing the attachment (G) protein of
      RSV results in pulmonary eosinophilia upon RSV challenge, whereas immunization of
      mice with a vv expressing the fusion (F) protein does not. We analyzed the CD4 T
      cell response to an I-E(d)-restricted CD4 T-cell epitope within the F protein of
      RSV corresponding to amino acids 51 to 66 in an effort to better understand the
      similarities and differences in the immune response elicited by the G versus the
      F protein. Vaccination with the G protein induces a mixture of RSV G-specific Th1
      and Th2 cells with a restricted T-cell receptor repertoire. In contrast, we
      demonstrate here that immunization with the F protein elicits a broad repertoire
      of RSV F-specific CD4 T cells that predominantly exhibit a Th1 phenotype.
      However, in the absence of gamma interferon (IFN-gamma), RSV F(51-66)-specific
      CD4 T cells secreted interleukin-5, and mice developed pulmonary eosinophilia
      after RSV challenge. IFN-gamma-deficient mice exhibited decreased weight loss
      compared to wild-type controls, suggesting that IFN-gamma exacerbates systemic
      disease. These data demonstrate that IFN-gamma can have both beneficial and
      detrimental effects during a secondary RSV infection.

PMID- 18094195
TI  - The forgotten role of lymphangitis in Crohn's disease.
AB  - Research into Crohn's disease has recently been focused on the genetics of the
      patient, the gastrointestinal flora, the gut epithelium and mucosal immune
      responses. For over 60 years pathologists have reported that the fundamental
      alteration in Crohn's disease occurs in regional lymphatics of the intestine--the
      disease is a lymphocytic and granulomatous lymphangitis. At an earlier time,
      experimental sclerosis of regional intestinal lymphatics of the pig produced a
      chronic segmental enteritis with many features of Crohn's disease, including
      lymphocytic and granulomatous lymphangitis of the bowel wall and enteroenteric
      and enterocutaneous fistulas. In Crohn's disease, differences in the anatomic
      distribution of vasa recta appear to explain long-segment disease of the ileum
      and short-segment disease of the more proximal intestine. A variety of bacteria
      and viruses cause lymphangitis, suggesting that microorganisms may be at the
      centre of the basic changes in Crohn's disease. Dietary antigens and lipids are
      worthy of consideration as well. Now that antibodies to label lymphatics are
      available, attention should be directed at defining the initial damage to
      lymphatic endothelium and agents that might be responsible.

PMID- 18094194
TI  - New mRNAs are preferentially translated during vesicular stomatitis virus
      infection.
AB  - During vesicular stomatitis virus (VSV) infection, host protein synthesis is
      inhibited, while synthesis of viral proteins increases. VSV infection causes
      inhibition of host transcription and RNA transport. Therefore, most host mRNAs in
      the cytoplasm of infected cells were synthesized before infection. However, viral
      mRNAs are synthesized throughout infection and are newer than preexisting host
      mRNAs. To determine if the timing of appearance of mRNAs in the cytoplasm
      affected their translation during VSV infection, we transfected reporter mRNAs
      into cells at various times relative to the time of infection and measured their
      rate of translation in mock- and VSV-infected cells. We found that translation of
      mRNAs transfected during infection was not inhibited but that translation of
      mRNAs transfected prior to infection was inhibited during VSV infection. Based on
      these data, we conclude that the timing of viral mRNA appearance in the cytoplasm
      is responsible, at least in part, for the preferential translation of VSV mRNAs.
      A time course measuring translation efficiencies of viral and host mRNAs showed
      that the translation efficiencies of viral mRNAs increased between 4 and 8 h
      postinfection, while translation efficiencies of host mRNAs decreased. The
      increased translation efficiency of viral mRNAs occurred in cells infected with
      an M protein mutant virus that is defective in host shutoff, demonstrating that
      the enhanced translation of viral mRNA is genetically separable from inhibition
      of translation of host mRNA.

PMID- 18094196
TI  - A peculiar gallbladder content.

PMID- 18094197
TI  - Evidence for mast cell involvement in human postoperative ileus: a novel link.

PMID- 18094198
TI  - Significance of increased human colonic permeability in response to
      corticotrophin-releasing hormone (CRH).

PMID- 18094199
TI  - Somatic mosaicism: a cause for unexplained cases of FAP?

PMID- 18094200
TI  - Predicting the development of hepatocellular cancer in hepatitis B carriers.

PMID- 18094201
TI  - Fulminant Clostridium difficile colitis.

PMID- 18094202
TI  - Massive haematemesis in an African male.

PMID- 18094203
TI  - Liver failure during pregnancy.

PMID- 18094204
TI  - A child with upper abdominal pain and pancreatitis.

PMID- 18094205
TI  - Guidelines on small bowel enteroscopy and capsule endoscopy in adults.

PMID- 18094206
TI  - Genetic testing is ready to change the diagnostic scenario of lactose
      malabsorption.

PMID- 18094207
TI  - Retinoids, bile acids and PPARs in Barrett's oesophagus.

PMID- 18094208
TI  - Avoiding the V-word: is volume therapy in hepatorenal syndrome killed by
      definition?

PMID- 18094212
TI  - Small bowel cancer: should relatives be screened for Lynch syndrome?

PMID- 18094213
TI  - Noninvasive quantitation of drug concentration in prostate and seminal vesicles:
      improvement and validation with desipramine and aspirin.
AB  - The accessory glands of the male genital tract are the sites of several major
      health problems, including benign prostatic hyperplasia, prostate cancer, and
      human immunodeficiency virus (HIV) transmission. We aimed to validate and improve
      our noninvasive method for the quantitation of drug concentrations in these
      physiological subcompartments. Twenty-seven men were dosed with 100 mg
      desipramine (a weak base) and 975 mg aspirin (a weak acid) and ejaculated their
      semen in 1 pass across 5 compartments of a collection device 2.5 hours later. A
      Bayesian latent-variable model previously developed by our group was further
      advanced for the estimation of drug concentrations in prostate and seminal
      vesicles based on drug and biomarker concentrations in the split ejaculate. Under
      normality assumptions, desipramine concentration (with 95% credible intervals) in
      prostate and seminal vesicles were 27 (8.3-52) ng/mL and 7.6 (4.0-11) ng/mL,
      respectively; salicylate concentration in prostate and seminal vesicles were 2.0
      (0.093-6.5) microg/mL, and 9.9 (8.2-12) microg/mL, respectively. The prostate-to
      seminal vesicles concentration ratio was 0.20 (0.0087-0.75) for salicylate and
      3.6 (0.91-9.9) for desipramine. We conclude that our quantitative analysis along
      with the split ejaculate method is sensitive, reproducible, and applicable for
      the assessment of pharmacokinetics of the accessory glands of the male genital
      tract.

PMID- 18094214
TI  - Commentary on the clinical relevance of concentration/QTc relationships for new
      drug candidates.

PMID- 18094215
TI  - A perspective on the use of concentration-QT modeling in drug development.

PMID- 18094216
TI  - Concentration-QT relationships play a key role in the evaluation of proarrhythmic
      risk during regulatory review.
AB  - The criterion for assessing whether a drug prolongs QT as described in the
      International Conference on Harmonization topic E14 guideline does not explicitly
      account for individual drug concentrations. The authors' experience with
      reviewing QT studies indicates that understanding the relationship, if any,
      between individual drug concentration and QT change provides important additional
      information to support regulatory decision making. Therefore, regulatory reviews
      of "thorough QT" studies routinely include a characterization of the
      concentration-QT relationship. The authors provide examples to illustrate how the
      concentration-QT relationship has been used to plan and interpret the thorough QT
      study, to evaluate QT risk for drugs that have no thorough QT studies, to assess
      QT risk in subpopulations, to make dose adjustments, and to write informative
      drug labels.

PMID- 18094218
TI  - Population pharmacokinetic investigation of actinomycin-D in children and young
      adults.
AB  - Actinomycin-D is an antineoplastic agent that inhibits RNA synthesis by binding
      to guanine residues and inhibiting DNA-dependent RNA polymerase. Although
      actinomycin-D has been used to treat rhabdomyosarcoma and Wilms tumor for more
      than 40 years, the dose/exposure relationship is not well characterized. The
      objective of this study was to develop an initial population pharmacokinetic
      model to describe actinomycin-D disposition in children and young adults from
      which a prospective study could be designed. A total of 165 actinomycin-D plasma
      concentration measurements from 33 patients, aged 1.6 to 20.3 years, were used
      for the analysis. The data were analyzed using nonlinear mixed-effects modeling
      with the NONMEM software system. Age, weight, and gender were examined as
      covariates for the ability to explain interindividual variability in actinomycin
      D pharmacokinetics. The final model was qualified via predictive check and
      nonparametric bootstrap procedures. A 3-compartment model with first-order
      elimination was chosen as the structural model. Allometric expressions
      incorporating weight were used to describe the effects of body size on
      actinomycin-D pharmacokinetics. Age and gender had no discernible effects on
      actinomycin-D pharmacokinetics in the population studied. The predictive check
      showed that the developed model was able to simulate data in close agreement with
      the actual study observations. The availability of an initial population
      pharmacokinetic model to describe actinomycin-D pharmacokinetics will facilitate
      the development of a large-scale clinical trial to study the actinomycin-D
      dose/exposure relationship in pediatric patients with rhabdomyosarcoma and Wilms
      tumor. The covariate analysis described by the current data set suggests that
      indices of body size captured via allometric expressions improve the partition of
      variation in actinomycin-D pharmacokinetics from this pilot data set.
      Relationships between pharmacokinetics and toxicity will be examined in future
      prospective studies in which children less than 1 year old will be enrolled.

PMID- 18094217
TI  - Dose proportionality of treprostinil sodium administered by continuous
      subcutaneous and intravenous infusion.
AB  - This study assessed the relationship between dose and plasma concentration
      following administration of treprostinil sodium infusion therapy in pulmonary
      arterial hypertension patients. This was a multicenter, open-label, multiple
      cohort, steady-state, pharmacokinetic study in subjects with pulmonary arterial
      hypertension receiving treprostinil by continuous intravenous or subcutaneous
      infusion at doses between 10 and 125 ng/kg/min. A blood sample was obtained from
      each patient at steady state and analyzed via a liquid chromatography/tandem mass
      spectrometry method. Forty-nine subjects receiving treprostinil were enrolled.
      Treprostinil doses ranged from 12.1 to 125 ng/kg/min; treprostinil plasma
      concentrations ranged from 14.9 to 18 248 pg/mL. Linear regression analysis
      revealed a correlation between treprostinil dose and treprostinil plasma
      concentration with an R2 value of 0.561. Using a power model to assess dose
      proportionality, the estimated nonproportionality parameter was 0.641 (95%
      confidence interval: 0.083-1.199), reflecting consistency with dose
      proportionality. Subset linear regression analysis, which excluded 2 subjects
      with anomalous treprostinil plasma concentrations, increased the R2 value to
      0.796. Using a power model to assess dose proportionality of this subset, the
      estimated nonproportionality parameter was 0.941 (95% confidence interval: 0.809
      1.073). This study supports previous findings of linearity at lower doses up to
      15 ng/kg/min and demonstrates linearity at treprostinil doses up to 125
      ng/kg/min.

PMID- 18094219
TI  - Prasugrel, a new thienopyridine antiplatelet drug, weakly inhibits cytochrome
      P450 2B6 in humans.
AB  - Prasugrel, a thienopyridine prodrug, is hydrolyzed in vivo by esterases to a
      thiolactone followed by a single cytochrome P450 (CYP)-dependent step to an
      active metabolite that is a potent inhibitor of adenosine diphosphate-induced
      platelet aggregation. This open-label, multiple-dose, 2-period, fixed-sequence
      study assessed CYP2B6 inhibition by prasugrel using bupropion as a probe
      substrate, where its active metabolite, hydroxybupropion, is almost exclusively
      formed by CYP2B6. Thirty healthy subjects received a single 150-mg oral dose of
      sustained-release bupropion. After a 7-day washout, a 60-mg prasugrel loading
      dose, followed by a 10-mg daily maintenance dose for 10 days, was administered.
      Bupropion (150 mg) was given with prasugrel on day 7 of this phase. Prasugrel
      weakly inhibited CYP2B6 activity as it increased bupropion Cmax and AUC0-infinity
      by 14% and 18%, respectively, and decreased hydroxybupropion Cmax and AUC0
      infinity by 32% and 23%. These results are consistent with patients receiving
      prasugrel not requiring dose adjustments when treated with drugs primarily
      metabolized by CYP2B6.

PMID- 18094220
TI  - Darunavir/ritonavir pharmacokinetics following coadministration with
      clarithromycin in healthy volunteers.
AB  - This study investigated the steady-state pharmacokinetic interaction between the
      HIV protease inhibitor, darunavir (TMC114), administered with low-dose ritonavir
      (darunavir/ritonavir), and clarithromycin in HIV-negative healthy volunteers. In
      a 3-way crossover study, 18 individuals received darunavir/ritonavir 400/100 mg
      bid, clarithromycin 500 mg bid, and darunavir/ritonavir 400/100 mg bid plus
      clarithromycin 500 mg bid in 3 separate sessions for 7 days, with a washout
      period of at least 7 days between treatments. Pharmacokinetic assessment was
      performed on day 7. Safety and tolerability of the study medication were
      monitored throughout. Coadministration of darunavir/ritonavir with clarithromycin
      resulted in a reduction in darunavir maximum plasma concentration (Cmax) and area
      under the curve from administration until 12 hours postdose (AUC12 h) of 17% and
      13%, respectively. Ritonavir Cmax and AUC12 h were unchanged. During
      coadministration with darunavir/ritonavir, clarithromycin Cmax and AUC12 h
      increased by 26% and 57%, respectively; 14-hydroxy-clarithromycin plasma
      concentrations were reduced to below the lower limit of quantification (<50
      ng/mL). The study medication was generally well tolerated. Based on these
      pharmacokinetic findings, neither clarithromycin nor darunavir/ritonavir dose
      adjustments are necessary when clarithromycin is coadministered with
      darunavir/ritonavir.

PMID- 18094221
TI  - Effect of rifampin, an inducer of CYP3A and P-glycoprotein, on the
      pharmacokinetics of risperidone.
AB  - The authors studied the effect of rifampin, a dual inducer of CYP3A and P
      glycoprotein, on the pharmacokinetics and pharmacodynamics of risperidone in
      humans. Ten healthy male subjects were treated daily for 7 days with 600 mg
      rifampin or with placebo. On day 6, a single dose of 1 mg risperidone was
      administered. Plasma risperidone and 9-hydroxyrisperidone concentrations were
      measured. Rifampin significantly decreased the mean area under the plasma
      concentration-time curve by 51% for risperidone, by 43% for 9-hydroxyrisperidone,
      and by 45% for the active moieties (risperidone + 9-hydroxyrisperidone). Rifampin
      also decreased the peak plasma concentration of risperidone by 38%, 9
      hydroxyrisperidone by 46%, and the active moieties by 41%. The apparent oral
      clearance of risperidone approximately doubled after rifampin treatment. Thus,
      rifampin reduced the exposure to risperidone, probably because of a decrease in
      its bioavailability through the induction of CYP3A and probably P-glycoprotein.

PMID- 18094222
TI  - Pharmacokinetics and metabolism of all-trans- and 13-cis-retinoic acid in
      pulmonary emphysema patients.
AB  - Retinoids promote lung alveolarization in animal models and were administered to
      patients as part of the Feasibility of Retinoid Therapy for Emphysema (FORTE)
      study. This FORTE substudy investigated the pharmacokinetic profiles of 2
      retinoic acid isomers-all-trans-retinoic acid (ATRA) and 13-cis-retinoic acid (13
      cRA)-in subjects with emphysema, evaluated strategies to overcome self-induced
      ATRA catabolism, and identified pharmacodynamic relationships. Comprehensive and
      limited pharmacokinetics were obtained at multiple visits in emphysema subjects
      treated with placebo (n = 30), intermittent dosing (4 days/week) with low-dose
      ATRA (1 mg/kg/day, n = 21), or high-dose ATRA (2 mg/kg/day, n = 25) or daily
      administration of 13-cRA (1 mg/kg/day, n = 40). High-dose ATRA produced the
      highest peak plasma ATRA Cmax. However, at follow-up, plasma ATRA C(max) was
      significantly decreased from baseline in subjects whose day 1 levels exceeded 100
      ng/mL (P < .0001). In contrast, administration of 13-cRA produced lower plasma
      ATRA C(max) (<100 ng/mL), but the levels were significantly higher at follow-up
      than those on day 1 (P < .001). Plasma ATRA levels as determined on day 1
      correlated with changes in pulmonary diffusing capacity at 6 months, consistent
      with concentration-dependent biologic effects (r2 = -0.25). The authors conclude
      that intermittent therapy with high-dose ATRA produced the greatest ATRA
      exposure, but alternative approaches for limiting self-induced ATRA catabolism
      should be sought.

PMID- 18094223
TI  - Systemic exposure and urinary cortisol effects of fluticasone propionate
      formulated with hydrofluoroalkane in 4- to 11-year-olds with asthma.
AB  - The systemic exposure of fluticasone propionate with hydrofluoroalkane propellant
      compared with chlorofluoro-carbon propellant and the effect of fluticasone
      propionate hydrofluoroalkane on 24-hour urinary cortisol in children aged 4 to 11
      years with asthma were evaluated. Study 1 was an open-label, 2-way crossover
      study in which 16 subjects were randomized to 7.5 days each of fluticasone
      propionate hydrofluoroalkane 88 mug twice a day or fluticasone propionate
      chlorofluorocarbon 88 mug twice a day. In study 2, 63 subjects received 13.5 days
      of placebo followed by 27.5 days of fluticasone propionate hydrofluoroalkane 88
      mug twice a day. The main outcome measure for study 1 was the difference between
      fluticasone propionate hydrofluoroalkane and fluticasone propionate
      chlorofluorocarbon in fluticasone propionate AUC(last) (area under the plasma
      fluticasone propionate concentration-time curve from zero up to the last
      quantifiable plasma concentration), and for study 2, 24-hour overnight urinary
      cortisol excretion. In study 1, fluticasone propionate systemic exposure was
      significantly lower (55%) with hydrofluoroalkane metered dose inhaler compared
      with chlorofluorocarbon metered dose inhaler. Study 2 showed no statistically
      significant changes in 24-hour overnight urinary cortisol excretion and no
      relationship to fluticasone propionate systemic exposure at this dose. The
      results of these 2 studies showed that in children aged 4 to 11 years with
      asthma, fluticasone propionate hydrofluoroalkane has lower systemic exposure
      compared with chlorofluorocarbon and no hypothalamic-pituitary-adrenal axis
      effects as measured by 24-hour urinary cortisol excretion.

PMID- 18094224
TI  - Effects of ibuprofen on the magnitude and duration of aspirin's inhibition of
      platelet aggregation: clinical consequences in stroke prophylaxis.
AB  - This study was designed to measure the magnitude and duration of inhibition of
      platelet aggregation following doses of aspirin or ibuprofen alone or taken in
      combination in a group of healthy volunteers. Ten normal volunteer subjects
      underwent 3 randomized treatment sessions: aspirin 325 mg alone, ibuprofen 400 mg
      alone, and ibuprofen 400 mg, followed by dosing with aspirin 325 mg 2 hours
      thereafter. In addition, a confirmatory study was performed in patients. Over 27
      months, a cohort of patients treated with aspirin for secondary stroke
      prophylaxis while concomitantly taking a nonsteroidal anti-inflammatory drug
      (NSAID) was identified. A significant reduction was found in both the magnitude
      and duration of aspirin's inhibitory effect on platelet aggregation when
      ibuprofen was given prior to aspirin administration in normal volunteer subjects.
      During a 27-month period, a cohort of 28 patients took regular daily doses of
      ibuprofen or naproxen. Of these 28 patients, 18 returned for follow-up testing in
      the absence of this pharmacodynamic interaction. None of these 18 patients
      demonstrated inhibition of platelet aggregation while on both NSAID and aspirin;
      however, all showed inhibition of aggregation following discontinuation of the
      NSAID. Notably, 13 of these 18 patients (72%) had experienced a recurrent
      ischemic episode while taking aspirin and NSAIDs concomitantly. These data
      suggest that ibuprofen prevents the irreversible inhibition of platelet
      aggregation produced by aspirin needed for secondary stroke prophylaxis, and this
      interaction can have clinical consequences for patients taking aspirin.

PMID- 18094225
TI  - Results of a study comparing the stability, efficacy, and adverse effect profile
      of innovator formulation, latanoprost (Xalatan) ophthalmic solution 0.005%, with
      that of a new formulation of a latanoprost ophthalmic solution containing
      cyclodextrins.

PMID- 18094227
TI  - Depression vulnerable and nonvulnerable smokers after a failure experience:
      examining cognitive self-regulation and motivation.
AB  - The present study extended previous tests of cognitive priming theories of
      depression by examining cognitive self-regulatory, motivational, and affective
      functioning of depression-vulnerable and nonvulnerable individuals after a
      failure experience. Participants were enrolled in a clinic-based smoking
      cessation program that consisted of seven group meetings. Major findings show
      that compared to the nonvulnerable group, depression-vulnerable individuals were
      less motivated to quit and experienced more negative affect, but only after a
      failure to quit smoking. However, after controlling for actual smoking rate,
      depression-vulnerable individuals did not evaluate their success any more
      negatively, nor did they indicate lower self-efficacy for quitting. Results are
      discussed in terms of cognitive self-regulatory and affect temperament models of
      motivation and depression.

PMID- 18094228
TI  - Endogenous inhibition and the neural basis of "free won't".

PMID- 18094229
TI  - Nature versus nurture in ventral visual cortex: a functional magnetic resonance
      imaging study of twins.
AB  - Using functional magnetic resonance imaging, we estimated neural activity in
      twins to study genetic influences on the cortical response to categories of
      visual stimuli (faces, places, and pseudowords) that are known to elicit distinct
      patterns of activity in ventral visual cortex. The neural activity patterns in
      monozygotic twins were significantly more similar than in dizygotic twins for the
      face and place stimuli, but there was no effect of zygosity for pseudowords (or
      chairs, a control category). These results demonstrate that genetics play a
      significant role in determining the cortical response to faces and places, but
      play a significantly smaller role (if any) in the response to orthographic
      stimuli.

PMID- 18094230
TI  - Plasticity of intrinsic excitability during long-term depression is mediated
      through mGluR-dependent changes in I(h) in hippocampal CA1 pyramidal neurons.
AB  - Bidirectional changes in synaptic strength are the proposed cellular correlate
      for information storage in the brain. Plasticity of intrinsic excitability,
      however, may also be critical for regulating the firing of neurons during
      mnemonic tasks. We demonstrated previously that the induction long-term
      potentiation was accompanied by a persistent decrease in CA1 pyramidal neuron
      excitability (Fan et al., 2005). We show here that induction of long-term
      depression (LTD) by 3 Hz pairing of back-propagating action potentials with
      Schaffer collateral EPSPs was accompanied by an overall increase in CA1 neuronal
      excitability. This increase was observed as an increase in the number of action
      potentials elicited by somatic current injection and was caused by an increase in
      neuronal input resistance. After LTD, voltage sag during hyperpolarizing current
      injections and subthreshold resonance frequency were decreased. All changes were
      blocked by ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium
      chloride), suggesting that a physiological loss of dendritic h-channels was
      responsible for the increase in excitability. Furthermore, block of group 1
      metabotropic glutamate receptors (mGluRs) or protein kinase C prevented the
      increase in excitability, whereas the group 1 mGluR agonist DHPG [(RS)-3,5
      dihydroxyphenylglycine] mimicked the effects. We conclude that 3 Hz synaptic
      stimulation downregulates I(h) via activation of group 1 mGluRs and subsequent
      stimulation of protein kinase C. We propose these changes as part of a
      homeostatic and bidirectional control mechanism for intrinsic excitability during
      learning.

PMID- 18094231
TI  - Topographic specificity within membranes of a single muscle detected in vitro.
AB  - Spinal motor pools project to target muscles forming distinct rostrocaudal
      topographic maps during development and regeneration. To define the mechanisms
      underlying these neuromuscular maps we studied the preferential outgrowth of
      embryonic spinal cord neurites on muscle membranes from different axial positions
      and explored the role of ephrin A ligands. We found all five ephrin As (EphAs)
      expressed in serratus anterior, gluteus maximus and diaphragm muscles. In the
      diaphragm, four of the five ephrin As are expressed as a caudal to rostral
      gradient. When ephrin A function is disrupted in muscle membranes by deletion of
      glycosyl-phosphatidylinositol anchored ephrin A ligands with phosphatidylinositol
      specific phospholipase C enzyme treatment or by blocking of ephrin A ligands with
      EphA fusion proteins, or by genetic manipulation leading to ephrin A2/A5 mutant
      mice, the spinal cord neurites loose their preference for the membranes of
      corresponding axial position; suggesting a significant role for ephrins in
      topographic choices made by growing motor neurons. To closely approximate
      topographic choices presented to embryonic neurites in vivo, neurites within the
      phrenic motor pool were challenged to make outgrowth choices on membranes of
      their normal target, the diaphragm muscle. We observed that neurites from rostral
      cervical segments (C1 and C2) prefer to grow on rostral diaphragm membranes;
      caudal cervical neurites (C6-C8) choose caudal diaphragm membranes; a transition
      of positional preference occurs at C4 and this ability is lost in ephrin A2/A5
      mutant mice. These results demonstrate for the first time topographical outgrowth
      of axons from within a motor pool onto a single target muscle in vitro.

PMID- 18094232
TI  - Two distinct heterotypic channels mediate gap junction coupling between astrocyte
      and oligodendrocyte connexins.
AB  - Genetic diseases demonstrate that the normal function of CNS myelin depends on
      connexin32 (Cx32) and Cx47, gap junction (GJ) proteins expressed by
      oligodendrocytes. GJs couple oligodendrocytes and astrocytes (O/A channels) as
      well as astrocytes themselves (A/A channels). Because astrocytes express
      different connexins (Cx30 and Cx43), O/A channels must be heterotypic, whereas
      A/A channels may be homotypic or heterotypic. Using electrophysiological and
      immunocytochemical approaches, we found that Cx47/Cx43 and Cx32/Cx30 efficiently
      formed functional channels, but other potential heterotypic O/A and A/A pairs did
      not. These results suggest that Cx30/Cx30 and Cx43/Cx43 channels mediate A/A
      coupling, and Cx47/Cx43 and Cx32/Cx30 channels mediate O/A coupling. Furthermore,
      Cx47/Cx43 and Cx32/Cx30 channels have distinct macroscopic and single-channel
      properties and different dye permeabilities. Finally, Cx47 mutants that cause
      Pelizaeus-Merzbacher-like disease do not efficiently form functional channels
      with Cx43, indicating that disrupted Cx47/Cx43 channels cause this disease.

PMID- 18094233
TI  - Decreased nociceptive sensitization in mice lacking the fragile X mental
      retardation protein: role of mGluR1/5 and mTOR.
AB  - Fragile X mental retardation is caused by silencing of the gene (FMR1) that
      encodes the RNA-binding protein (FMRP) that influences translation in neurons. A
      prominent feature of the human disorder is self-injurious behavior, suggesting an
      abnormality in pain processing. Moreover, FMRP regulates group I metabotropic
      glutamate receptor (mGluR1/5)-dependent plasticity, which is known to contribute
      to nociceptive sensitization. We demonstrate here, using the Fmr1 knock-out (KO)
      mouse, that FMRP plays an important role in pain processing because Fmr1 KO mice
      showed (1) decreased (approximately 50%) responses to ongoing nociception (phase
      2, formalin test), (2) a 3 week delay in the development of peripheral nerve
      injury-induced allodynia, and (3) a near absence of wind-up responses in
      ascending sensory fibers after repetitive C-fiber stimulation. We provide
      evidence that the behavioral deficits are related to a mGluR1/5- and mammalian
      target of rapamycin (mTOR)-mediated mechanism because (1) spinal mGluR5
      antagonism failed to inhibit the second phase of the formalin test, and we
      observed a marked reduction in nociceptive response to an intrathecal injection
      of an mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) in Fmr1 KO mice;
      (2) peripheral DHPG injection had no effect in KO mice yet evoked thermal
      hyperalgesia in wild types; and (3) the mTOR inhibitor rapamycin inhibited
      formalin- and DHPG-induced nociception in wild-type but not Fmr1 KO mice. These
      experiments show that translation regulation via FMRP and mTOR is an important
      feature of nociceptive plasticity. These observations also support the hypothesis
      that the persistence of self-injurious behavior observed in fragile X mental
      retardation patients could be related to deficits in nociceptive sensitization.

PMID- 18094235
TI  - Inactivation of the lateral but not medial dorsal striatum eliminates the
      excitatory impact of Pavlovian stimuli on instrumental responding.
AB  - Conditioned stimuli are important guides for behavioral actions. This experiment
      determined the role of the dorsal striatum in conditioned-stimulus modulation of
      instrumental responding using the pavlovian-instrumental transfer (PIT) paradigm.
      Rats received pavlovian training wherein two different auditory stimuli predicted
      the delivery of two food rewards. Next, rats were trained to perform two
      instrumental actions earning the same two rewards. Finally, the impact of
      pavlovian stimuli on instrumental performance was assessed in extinction: the
      stimuli were periodically presented while rats were free to perform the lever
      press response. Before testing, medial or lateral dorsal striatum was infused
      with saline or baclofen/muscimol, to temporarily inactivate the region. Under
      saline, outcome-selective PIT was observed: presentation of a stimulus paired
      with the same outcome as the instrumental action elevated responding, whereas
      presentation of a stimulus paired with a different outcome did not. Inactivation
      of the dorsolateral striatum dramatically reduced this effect. Inactivation of
      the dorsomedial striatum left intact the ability of reward-related stimuli to
      invigorate responding; however, the selectivity of the stimulus effect was lost
      (i.e., both stimuli excited responding). These results indicate that subregions
      of the dorsal striatum play distinct roles in stimulus modulation of instrumental
      performance with the lateral region being vital for reward-related stimuli to
      excite responding and the medial region being involved in the integration of
      stimulus-reward associations with specific response-outcome associations to
      produce selective responding. These findings identify new roles for the dorsal
      striatum in mediating the incentive effects of reward-predictive stimuli on
      behavioral actions made to obtain reward.

PMID- 18094234
TI  - Repeated N-acetylcysteine administration alters plasticity-dependent effects of
      cocaine.
AB  - Cocaine produces a persistent reduction in cystine-glutamate exchange via system
      x(c)- in the nucleus accumbens that may contribute to pathological glutamate
      signaling linked to addiction. System x(c)- influences glutamate
      neurotransmission by maintaining basal, extracellular glutamate in the nucleus
      accumbens, which, in turn, shapes synaptic activity by stimulating group II
      metabotropic glutamate autoreceptors. In the present study, we tested the
      hypothesis that a long-term reduction in system x(c)- activity is part of the
      plasticity produced by repeated cocaine that results in the establishment of
      compulsive drug seeking. To test this, the cysteine prodrug N-acetylcysteine was
      administered before daily cocaine to determine the impact of increased cystine
      glutamate exchange on the development of plasticity-dependent cocaine seeking.
      Although N-acetylcysteine administered before cocaine did not alter the acute
      effects of cocaine on self-administration or locomotor activity, it prevented
      behaviors produced by repeated cocaine including escalation of drug intake,
      behavioral sensitization, and cocaine-primed reinstatement. Because sensitization
      or reinstatement was not evident even 2-3 weeks after the last injection of N
      acetylcysteine, we examined whether N-acetylcysteine administered before daily
      cocaine also prevented the persistent reduction in system x(c)- activity produced
      by repeated cocaine. Interestingly, N-acetylcysteine pretreatment prevented
      cocaine-induced changes in [35S]cystine transport via system x(c)-, basal
      glutamate, and cocaine-evoked glutamate in the nucleus accumbens when assessed at
      least 3 weeks after the last N-acetylcysteine pretreatment. These findings
      indicate that N-acetylcysteine selectively alters plasticity-dependent behaviors
      and that normal system x(c)- activity prevents pathological changes in
      extracellular glutamate that may be necessary for compulsive drug seeking.

PMID- 18094236
TI  - The G59S mutation in p150(glued) causes dysfunction of dynactin in mice.
AB  - The G59S missense mutation at the conserved microtubule-binding domain of
      p150(glued), a major component of dynein/dynactin complex, has been linked to an
      autosomal dominant form of motor neuron disease (MND). To study how this mutation
      affects the function of the dynein/dynactin complex and contributes to motor
      neuron degeneration, we generated p150(glued) G59S knock-in mice. We found that
      the G59S mutation destabilizes p150(glued) and disrupts the function of
      dynein/dynactin complex, resulting in early embryonic lethality of homozygous
      knock-in mice. Heterozygous knock-in mice, which developed normally, displayed
      MND-like phenotypes after 10 months of age, including excessive accumulation of
      cytoskeletal and synaptic vesicle proteins at neuromuscular junctions, loss of
      spinal motor neurons, increase of reactive astrogliosis, and shortening of gait
      compared with wild-type littermates and age-matched p150(glued) heterozygous
      knock-out mice. Our findings indicate that the G59S mutation in p150(glued)
      abrogates the normal function of p150(glued) and accelerates motor neuron
      degeneration.

PMID- 18094237
TI  - The adult mouse subependymal zone regenerates efficiently in the absence of
      tenascin-C.
AB  - The subependymal zone (SEZ) of the lateral ventricles of the adult mouse brain
      hosts neurogenesis from a neural stem cell population with the morphology of
      astrocytes (termed type-B cells). Tenascin-C is a large extracellular matrix
      glycoprotein present in the SEZ that has been shown to regulate the development
      of embryonic neural stem cells and the proliferation and migration of early
      postnatal neural precursors. Here we show that tenascin-C is produced by type-B
      cells and forms a layer between SEZ and the adjacent striatum. Tenascin-C
      deficiency resulted in minor structural differences in and around the SEZ.
      However, the numbers of neural stem cells and their progeny remained unaffected,
      as did their regeneration after depletion of mitotic cells using the antimitotic
      drug cytosine-beta-D-arabinofuranoside. Our results reveal a remarkable ability
      of the adult neural stem cell niche to retain proper function even after the
      removal of major extracellular matrix molecules.

PMID- 18094238
TI  - Inducible alterations of glutathione levels in adult dopaminergic midbrain
      neurons result in nigrostriatal degeneration.
AB  - Parkinson's disease is a neurodegenerative disorder characterized by the
      preferential loss of midbrain dopaminergic neurons in the substantia nigra (SN).
      One of the earliest detectable biochemical alterations that occurs in the
      Parkinsonian brain is a marked reduction in SN levels of total glutathione
      (glutathione plus glutathione disulfide), occurring before losses in
      mitochondrial complex I (CI) activity, striatal dopamine levels, or midbrain
      dopaminergic neurodegeneration associated with the disease. Previous in vitro
      data from our laboratory has suggested that prolonged depletion of dopaminergic
      glutathione results in selective impairment of mitochondrial complex I activity
      through a reversible thiol oxidation event. To address the effects of depletion
      in dopaminergic glutathione levels in vivo on the nigrostriatal system, we
      created genetically engineered transgenic mouse lines in which expression of
      gamma-glutamyl cysteine ligase, the rate-limiting enzyme in de novo glutathione
      synthesis, can be inducibly downregulated in catecholaminergic neurons, including
      those of the SN. A novel method for isolation of purified dopaminergic striatal
      synaptosomes was used to study the impact of dopaminergic glutathione depletion
      on mitochondrial events demonstrated previously to occur in vitro as a
      consequence of this alteration. Dopaminergic glutathione depletion was found to
      result in a selective reversible thiol-oxidation-dependent mitochondrial complex
      I inhibition, followed by an age-related nigrostriatal neurodegeneration. This
      suggests that depletion in glutathione within dopaminergic SN neurons has a
      direct impact on mitochondrial complex I activity via increased nitric oxide
      related thiol oxidation and age-related dopaminergic SN cell loss.

PMID- 18094239
TI  - Synaptic strength of individual spines correlates with bound Ca2+-calmodulin
      dependent kinase II.
AB  - Both synaptic strength and spine size vary from spine to spine, but are strongly
      correlated. This gradation is regulated by activity and may underlie information
      storage. Ca2+-calmodulin-dependent kinase II (CaMKII) is critically involved in
      the regulation of synaptic strength and spine size. The high amount of the kinase
      in the postsynaptic density has suggested that the kinase has a structural role
      at synapses. We demonstrated previously that the bound amount of CaMKIIalpha in
      spines persistently increases after induction of long-term potentiation,
      prompting the hypothesis that this amount may correlate with synaptic strength.
      To test this hypothesis we combined two recently developed methods, two-photon
      uncaging of glutamate for determining the EPSC of individual spines (uEPSC) and
      quantitative microscopy for measuring bound CaMKIIalpha in the same spines. We
      found that under basal conditions the relative bound amount of CaMKIIalpha varied
      over a 10-fold range and positively correlated with the uEPSC. Both the bound
      amount of CaMKIIalpha in spines and uEPSC also positively correlated with spine
      size. Interestingly, the bound CaMKIIalpha fraction (bound/total CaMKIIalpha in
      spines) remained remarkably constant across all spines. The results are
      consistent with the hypothesis that bound CaMKII serves as a structural organizer
      of postsynaptic molecules and thereby may be involved in maintaining spine size
      and synaptic strength.

PMID- 18094240
TI  - Disrupted dentate granule cell chloride regulation enhances synaptic excitability
      during development of temporal lobe epilepsy.
AB  - GABA(A) receptor-mediated inhibition depends on the maintenance of intracellular
      Cl- concentration ([Cl-]in) at low levels. In neurons in the developing CNS, [Cl
      ]in is elevated, E(GABA) is depolarizing, and GABA consequently is excitatory.
      Depolarizing GABAergic synaptic responses may be recapitulated in various
      neuropathological conditions, including epilepsy. In the present study, rat
      hippocampal dentate granule cells were recorded using gramicidin perforated patch
      techniques at varying times (1-60 d) after an epileptogenic injury, pilocarpine
      induced status epilepticus (STEP). In normal, non-epileptic animals, these
      strongly inhibited dentate granule cells act as a gate, regulating hippocampal
      excitation, controlling seizure initiation and/or propagation. For 2 weeks after
      STEP, we found that E(GABA) was positively shifted in granule cells. This shift
      in E(GABA) altered synaptic integration, increased granule cell excitability, and
      resulted in compromised "gate" function of the dentate gyrus. E(GABA) recovered
      to control values at longer latencies post-STEP (2-8 weeks), when animals had
      developed epilepsy. During this period of shifted E(GABA), expression of the Cl-
      extruding K+/Cl- cotransporter, KCC2 was decreased. Application of the KCC2
      blocker, furosemide, to control neurons mimicked E(GABA) shifts evident in
      granule cells post-STEP. Furthermore, post-STEP and furosemide effects interacted
      occlusively, both on E(GABA) in granule cells, and on gatekeeper function of the
      dentate gyrus. This suggests a shared mechanism, reduced KCC2 function. These
      findings demonstrate that decreased expression of KCC2 persists for weeks after
      an epileptogenic injury, reducing inhibitory efficacy and enhancing dentate
      granule cell excitability. This pathophysiological process may constitute a
      significant mechanism linking injury to the subsequent development of epilepsy.

PMID- 18094241
TI  - Reciprocal regulation of presynaptic and postsynaptic proteins in bipolar spiral
      ganglion neurons by neurotrophins.
AB  - A unifying principle of sensory system organization is feature extraction by
      modality-specific neuronal maps in which arrays of neurons show systematically
      varied response properties and receptive fields. Only beginning to be understood,
      however, are the mechanisms by which these graded systems are established. In the
      peripheral auditory system, we have shown previously that the intrinsic firing
      features of spiral ganglion neurons are influenced by brain-derived neurotrophic
      factor (BDNF) and neurotrophin-3 (NT-3). We now show that is but a part of a
      coordinated package of neurotrophin actions that also includes effects on
      presynaptic and postsynaptic proteins, thus encompassing the input, transmission,
      and output functions of the spiral ganglion neurons. Using immunocytochemical
      methods, we determined that proteins targeted to opposite ends of the neuron were
      organized and regulated in a reciprocal manner. AMPA receptor subunits GluR2 and
      GluR3 were enriched in base neurons compared with their apex counterparts. This
      distribution pattern was enhanced by exposure to BDNF but reduced by NT-3. SNAP
      25 and synaptophysin were distributed and regulated in the mirror image: enriched
      in the apex, enhanced by NT-3 and reduced by BDNF. Moreover, we used a novel
      coculture to identify potential endogenous sources of neurotrophins by showing
      that sensory receptors from different cochlear regions were capable of altering
      presynaptic and postsynaptic protein levels in these neurons. From these studies,
      we suggest that BDNF and NT-3, which are systematically distributed in
      complementary gradients, are responsible for orchestrating a comprehensive set of
      electrophysiological specializations along the frequency contour of the cochlea.

PMID- 18094242
TI  - Neural substrates of abstinence-induced cigarette cravings in chronic smokers.
AB  - Craving is a hallmark of drug dependence, including dependence on nicotine. Many
      studies have examined the neural substrates of cravings elicited by smoking
      related cues. Less is known about the neural basis of unprovoked, abstinence
      induced cravings, despite the contributions of such cravings to smoking relapse.
      To fill this gap, we used arterial spin labeled (ASL) perfusion magnetic
      resonance imaging to characterize the neural substrates of abstinence-induced
      cravings to smoke. Fifteen chronic smokers were scanned during a resting state on
      two separate occasions: (1) smoking satiety and (2) abstinence (after > or = 12 h
      of smoking deprivation), in counterbalanced order. Smoking abstinence state (vs
      satiety) was associated with increased cerebral blood flow (CBF) in anterior
      cingulate cortex (ACC)/medial orbitofrontal cortex (OFC) and left OFC. Abstinence
      induced cravings to smoke were predicted by CBF increases (abstinence minus
      satiety) in the right OFC, right dorsolateral prefrontal cortex, occipital
      cortex, ACC, ventral striatum/nucleus accumbens, thalamus, amygdala, bilateral
      hippocampus, left caudate, and right insula. These data suggest that increased
      activation in the brain's visuospatial and reward circuitry underlies abstinence
      induced cravings to smoke, and thereby, may be important in relapse.

PMID- 18094243
TI  - Effects of saporin-induced lesions of three arousal populations on daily levels
      of sleep and wake.
AB  - The hypocretin (HCRT) neurons are located only in the perifornical area of the
      lateral hypothalamus and heavily innervate the cholinergic neurons in the basal
      forebrain (BF), histamine neurons in the tuberomammillary nucleus (TMN), and the
      noradrenergic locus ceruleus (LC) neurons, three neuronal populations that have
      traditionally been implicated in regulating arousal. Based on the innervation,
      HCRT neurons may regulate arousal by driving these downstream arousal neurons.
      Here, we directly test this hypothesis by a simultaneous triple lesion of these
      neurons using three saporin-conjugated neurotoxins. Three weeks after lesion, the
      daily levels of wake were not changed in rats with double or triple lesions,
      although rats with triple lesions were asleep more during the light-to-dark
      transition period. The double- and triple-lesioned rats also had more stable
      sleep architecture compared with nonlesioned saline rats. These results suggest
      that the cholinergic BF, TMN, and LC neurons jointly modulate arousal at a
      specific circadian time, but they are not essential links in the circuitry
      responsible for daily levels of wake, as traditionally hypothesized.

PMID- 18094244
TI  - TASK channels determine pH sensitivity in select respiratory neurons but do not
      contribute to central respiratory chemosensitivity.
AB  - Central respiratory chemoreception is the mechanism by which the CNS maintains
      physiologically appropriate pH and PCO2 via control of breathing. A prominent
      hypothesis holds that neural substrates for this process are distributed widely
      in the respiratory network, especially because many neurons that make up this
      network are chemosensitive in vitro. We and others have proposed that TASK
      channels (TASK-1, K(2P)3.1 and/or TASK-3, K(2P)9.1) may serve as molecular
      sensors for central chemoreception because they are highly expressed in multiple
      neuronal populations in the respiratory pathway and contribute to their pH
      sensitivity in vitro. To test this hypothesis, we examined the chemosensitivity
      of two prime candidate chemoreceptor neurons in vitro and tested ventilatory
      responses to CO2 using TASK channel knock-out mice. The pH sensitivity of
      serotonergic raphe neurons was abolished in TASK channel knock-outs. In contrast,
      pH sensitivity of neurons in the mouse retrotrapezoid nucleus (RTN) was fully
      maintained in a TASK null background, and pharmacological evidence indicated that
      a K+ channel with properties distinct from TASK channels contributes to the pH
      sensitivity of rat RTN neurons. Furthermore, the ventilatory response to CO2 was
      completely retained in single or double TASK knock-out mice. These data rule out
      a strict requirement for TASK channels or raphe neurons in central respiratory
      chemosensation. Furthermore, they indicate that a non-TASK K+ current contributes
      to chemosensitivity of RTN neurons, which are profoundly pH-sensitive and capable
      of driving respiratory output in response to local pH changes in vivo.

PMID- 18094245
TI  - Multiple sites for generation of ectopic spontaneous activity in neurons of the
      chronically compressed dorsal root ganglion.
AB  - In a chronically compressed dorsal root ganglion (CCD) in the rat, a model of
      foraminal stenosis and radicular pain in human, a subpopulation of neurons with
      functional axons exhibits spontaneous activity (SA) that originates within the
      ganglion. Intracellular electrophysiological recordings were obtained from the
      somata of neurons of the compressed ganglion both in vitro and in vivo. The SA
      was classified into two types according to the presence (type I) or absence (type
      II) of subthreshold membrane potential oscillation. Neurons with type I SA had
      significantly higher somal excitability than those with type II SA. In most
      cases, depolarization of the membrane potential by current injection increased
      the discharge rates of type I--but not type II SA. Both types occasionally
      coexisted in the same neuron. Several lines of evidence suggested that the origin
      of SA in the DRG was most likely the soma for type I SA and the axon for type II.
      Therefore CCD neurons have multiple sites for generation of action potentials
      other than the terminal endings. In vivo recordings revealed the same two types
      of SA in a subpopulation of neurons with functionally characterized peripheral
      receptive fields. Thus, SA might not only produce spurious sensory input to the
      afferent pathways but also add to or block impulse transmission generated by
      natural stimulation of peripheral receptors. SA originating in the compressed
      ganglion is likely to interfere with sensory transmission in nociceptive and non
      nociceptive neurons, thereby contributing to radicular pain, paresthesias,
      hyperalgesia and allodynia.

PMID- 18094246
TI  - Estradiol in vivo regulation of brain mitochondrial proteome.
AB  - We used a combined proteomic and functional biochemical approach to determine the
      overall impact of 17beta-estradiol (E2) on mitochondrial protein expression and
      function. To elucidate mitochondrial pathways activated by E2 in brain, two
      dimensional (2D) gel electrophoresis was conducted to screen the mitoproteome.
      Ovariectomized adult female rats were treated with a single injection of E2.
      After 24 h of E2 exposure, mitochondria were purified from brain and 2D analysis
      and liquid chromatography-tandem mass spectrometry protein identification were
      conducted. Results of proteomic analyses indicated that of the 499 protein spots
      detected by image analysis, a total of 66 protein spots had a twofold or greater
      change in expression. Of these, 28 proteins were increased in expression after E2
      treatment whereas 38 proteins were decreased in expression relative to control.
      E2 regulated key metabolic enzymes including pyruvate dehydrogenase, aconitase,
      and ATP-synthase. To confirm that E2-inducible changes in protein expression
      translated into functional consequences, we determined the impact of E2 on the
      enzymatic activity of the mitochondrial electron transport chain. In vivo, E2
      treatment enhanced brain mitochondrial efficiency as evidenced by increased
      respiratory control ratio, elevated cytochrome-c oxidase activity and expression
      while simultaneously reducing free radical generation in brain. Results of these
      analyses provide insights into E2 mechanisms of regulating brain mitochondria,
      which have the potential for sustaining neurological health and prevention of
      neurodegenerative diseases associated with mitochondrial dysfunction such as
      Alzheimer's disease.

PMID- 18094247
TI  - Auditory neurons make stereotyped wiring decisions before maturation of their
      targets.
AB  - Cochlear ganglion neurons communicate sound information from cochlear hair cells
      to auditory brainstem neurons through precisely wired circuits. Understanding
      auditory circuit assembly is a significant challenge because of the small size of
      the otic vesicle and difficulties labeling and imaging embryonic neurons. We used
      genetic fate mapping in the mouse to visualize the morphologies of individual
      cochlear ganglion neurons throughout development, from their origin in the
      Neurogenin1-positive neurogenic domain in the otic vesicle to the formation of
      connections with targets in the cochlea and in the cochlear nucleus. We found
      that auditory neurons with different patterns of connectivity arise from discrete
      populations of Neurogenin1-positive precursors that make stereotyped wiring
      decisions depending on when and where they are born. Auditory precursors are
      segregated from vestibular precursors early in neurogenesis. Within this
      population, cochlear ganglion neurons with type I and type II morphologies are
      apparent before birth and develop within common pools of precursors. The
      peripheral projections are initially complex and branched and then become simple
      and straight after reaching the edge of the sensory epithelium. Subsequently, a
      small number of projections attain obvious type II morphologies, beginning at
      embryonic day 16.5 (E16.5), when hair cells begin to differentiate. Centrally,
      cochlear ganglion axons are topographically organized in the auditory brainstem
      as early as E15.5, when the cochlear nucleus is still immature. These findings
      suggest that Neurogenin1 precursors possess intrinsic programs of differentiation
      that direct early auditory circuit assembly events before the maturation of
      presynaptic and postsynaptic target cells.

PMID- 18094248
TI  - Nanoscale organization of the MEC-4 DEG/ENaC sensory mechanotransduction channel
      in Caenorhabditis elegans touch receptor neurons.
AB  - Hearing, touch and proprioception are thought to involve direct activation of
      mechano-electrical transduction (MeT) channels. In Caenorhabditis elegans touch
      receptor neurons (TRNs), such channels contain two pore-forming subunits (MEC-4
      and MEC-10) and two auxiliary subunits (MEC-2 and MEC-6). MEC-4 and MEC-10 belong
      to a large superfamily of ion channel proteins (DEG/ENaCs) that form nonvoltage
      gated, amiloride-sensitive Na+ channels. In TRNs, unique 15-protofilament
      microtubules and an electron-dense extracellular matrix have been proposed to
      serve as gating tethers critical for MeT channel activation. We combined high
      pressure freezing and serial-section immunoelectron microscopy to determine the
      position of MeT channels relative to putative gating tethers. MeT channels were
      visualized using antibodies against MEC-4 and MEC-2. This nanometer-resolution
      view of a sensory MeT channel establishes structural constraints on the mechanics
      of channel gating. We show here that MEC-2 and MEC-5 collagen, a putative
      extracellular tether, occupy overlapping but distinct domains in TRN neurites.
      Although channels decorate all sides of TRN neurites; they are not associated
      with the distal endpoints of 15-protofilament microtubules hypothesized to be
      gating tethers. These specialized microtubules, which are unique to TRNs,
      assemble into a cross-linked bundle connected by a network of kinked filaments to
      the neurite membrane. We speculate that the microtubule bundle converts external
      point loads into membrane stretch which, in turn, facilitates MeT channel
      activation.

PMID- 18094249
TI  - Lim1 is essential for the correct laminar positioning of retinal horizontal
      cells.
AB  - Although much is known about the transcriptional regulation that coordinates
      retinal cell fate determination, very little is known about the developmental
      processes that establish the characteristic laminar architecture of the retina,
      in particular, the specification of neuronal positioning. The LIM class
      homeodomain transcription factor Lim1 (Lhx1) is expressed in postmitotic,
      differentiating, and mature retinal horizontal cells. We show that conditional
      ablation of Lim1 results in the ectopic localization of horizontal cells to inner
      aspects of the inner nuclear layer, among the retinal amacrine cells. The ectopic
      cells maintain a molecular phenotype consistent with horizontal cell identity;
      however, these neurons adopt a unique morphology more reminiscent of amacrine
      cells, including a dendritic arbor positioned within the inner plexiform layer.
      All other retinal cell populations appear unaltered. Our data suggest a model
      whereby Lim1 lies downstream of horizontal cell fate determination factors and
      functions cell autonomously to instruct differentiating horizontal cells to the
      appropriate laminar position in the developing retina. This study is the first to
      describe a cell type-specific genetic program that is essential for targeting a
      discrete retinal neuron population to the proper lamina.

PMID- 18094250
TI  - GABA(A) receptor gamma 2 subunit mutations linked to human epileptic syndromes
      differentially affect phasic and tonic inhibition.
AB  - GABA acts on GABA(A) receptors to evoke both phasic inhibitory synaptic events
      and persistent, tonic currents. The gamma2 subunit of the GABA(A) receptor is
      involved in both phasic and tonic signaling in the hippocampus. Several mutations
      of this subunit are linked to human epileptic syndromes with febrile seizures,
      yet it is not clear how they perturb neuronal activity. Here, we examined the
      expression and functional impact of recombinant gamma2 in hippocampal neurons. We
      show that the K289M mutation has no effect on membrane trafficking and synaptic
      aggregation of recombinant gamma2, but accelerates the decay of synaptic
      currents. In contrast, the R43Q mutation primarily reduces surface expression of
      recombinant gamma2. However, it has no dominant effect on synaptic currents but
      instead reduces tonic GABA currents, at least in part by reducing surface
      expression of the alpha5 subunit. Our data suggests that the phenotypic
      specificity of mutations affecting the GABA(A) receptor gamma2 gene may result
      from different actions specific to distinct modes of GABAergic signaling.

PMID- 18094251
TI  - Expression and localization of RGS9-2/G 5/R7BP complex in vivo is set by dynamic
      control of its constitutive degradation by cellular cysteine proteases.
AB  - A member of regulator of G-protein signaling family, RGS9-2, is an essential
      modulator of signaling through neuronal dopamine and opioid G-protein-coupled
      receptors. Recent findings indicate that the abundance of RGS9-2 determines
      sensitivity of signaling in the locomotor and reward systems in the striatum. In
      this study we report the mechanism that sets the concentration of RGS9-2 in vivo,
      thus controlling G-protein signaling sensitivity in the region. We found that
      RGS9-2 possesses specific degradation determinants which target it for
      constitutive destruction by lysosomal cysteine proteases. Shielding of these
      determinants by the binding partner R7 binding-protein (R7BP) controls RGS9-2
      expression at the posttranslational level. In addition, binding to R7BP in
      neurons targets RGS9-2 to the specific intracellular compartment, the
      postsynaptic density. Implementation of this mechanism throughout ontogenetic
      development ensures expression of RGS9-2/type 5 G-protein beta subunit/R7BP
      complexes at postsynaptic sites in unison with increased signaling demands at
      mature synapses.

PMID- 18094252
TI  - Serotonergic neurons activate chemosensitive retrotrapezoid nucleus neurons by a
      pH-independent mechanism.
AB  - Serotonin activates respiration and enhances the stimulatory effect of CO2 on
      breathing. The present study tests whether the mechanism involves the
      retrotrapezoid nucleus (RTN), a group of medullary glutamatergic neurons
      activated by extracellular brain pH and presumed to regulate breathing. We show
      that the RTN is innervated by both medullary and pontine raphe and receives
      inputs from thyrotropin-releasing hormone (TRH) and substance P-expressing
      neurons. Coexistence of serotonin and substance P in terminals within RTN
      confirmed that lower medullary serotonergic neurons innervate RTN. In vivo,
      unilateral injection of serotonin into RTN stimulated inspiratory motor activity,
      and pH-sensitive RTN neurons were activated by iontophoretic application of
      serotonin or substance P. In brain slices, pH-sensitive RTN neurons were
      activated by serotonin, substance P, and TRH. The effect of serotonin in slices
      was ketanserin sensitive and persisted in the presence of glutamate, GABA,
      glycine, and purinergic ionotropic receptor antagonists. Serotonin and pH had
      approximately additive effects on the discharge rate of RTN neurons, both in
      slices and in vivo. In slices, serotonin produced an inward current with little
      effect on conductance and had no effect on the pH-induced current. We conclude
      that (1) RTN receives input from multiple raphe nuclei, (2) serotonin, substance
      P, and TRH activate RTN chemoreceptors, and (3) excitatory effects of serotonin
      and pH are mediated by distinct ionic conductances. Thus, RTN neurons presumably
      contribute to the respiratory stimulation caused by serotonergic neurons, but
      serotonin seems without effect on the cellular mechanism by which RTN neurons
      detect pH.

PMID- 18094253
TI  - Differential effects of recombinant adeno-associated virus-mediated neuropeptide
      Y overexpression in the hypothalamic paraventricular nucleus and lateral
      hypothalamus on feeding behavior.
AB  - It is well known that neuropeptide Y (NPY) increases food intake. The
      hypothalamic paraventricular nucleus (PVN) and the lateral hypothalamus (LH) are
      both involved in the acute, hyperphagic effects of NPY. Although it is obvious
      that increased energy intake may lead to obesity, it is less understood which
      aspects of feeding behavior are affected and whether one or multiple neural sites
      mediate the effects of long-term increased NPY signaling. By long-term
      overexpressing NPY in either the PVN or the LH, we uncovered brain site-specific
      effects of NPY on meal frequency, meal size, and diurnal feeding patterns. In
      rats injected with adeno-associated virus-NPY in the PVN, increased food intake
      resulted from an increase in the amount of meals consumed, whereas in rats
      injected in the LH, increased food intake was attributable to increased meal
      size. Interestingly, food intake and body weight gain were only temporarily
      increased in PVN-injected rats, whereas in LH-injected rats hyperphagia and body
      weight gain remained for the entire 50 d. Moreover, in LH-NPY rats, but not in
      PVN-NPY rats, diurnal rhythmicity with regard to food intake and body core
      temperature was lost. These data clearly show that the NPY system differentially
      regulates energy intake and energy expenditure in the PVN and LH, which together
      adjust energy balance.

PMID- 18094255
TI  - The axon-dendrite targeting of Kv3 (Shaw) channels is determined by a targeting
      motif that associates with the T1 domain and ankyrin G.
AB  - Kv3 (Shaw) channels regulate rapid spiking, transmitter release and dendritic
      integration of many central neurons. Crucial to functional diversity are the
      complex targeting patterns of channel proteins. However, the targeting mechanisms
      are not known. Here we report that the axon-dendrite targeting of Kv3.1 is
      controlled by a conditional interaction of a C-terminal axonal targeting motif
      (ATM) with the N-terminal T1 domain and adaptor protein ankyrin G. In cultured
      hippocampal neurons, although the two splice variants of Kv3.1, Kv3.1a and
      Kv3.1b, are differentially targeted to the somatodendritic and axonal membrane,
      respectively, the lysine-rich ATM is surprisingly common for both splice
      variants. The ATM not only directly binds to the T1 domain in a Zn2+-dependent
      manner, but also associates with the ankyrin-repeat domain of ankyrin G. However,
      the full-length channel proteins of Kv3.1b display stronger association to
      ankyrin G than those of Kv3.1a, suggesting that the unique splice domain at
      Kv3.1b C terminus influences ATM binding to T1 and ankyrin G. Because ankyrin G
      mainly resides at the axon initial segment, we propose that it may function as a
      barrier for axon-dendrite targeting of Kv3.1 channels. In support of this idea,
      disrupting ankyrin G function either by over-expressing a dominant-negative
      mutant or by siRNA knockdown decreases polarized axon-dendrite targeting of both
      Kv3.1a and Kv3.1b. We conclude that the conditional ATM masked by the T1 domain
      in Kv3.1a is exposed by the splice domain in Kv3.1b, and is subsequently
      recognized by ankyrin G to target Kv3.1b into the axon.

PMID- 18094254
TI  - Diversity in the neural circuitry of cold sensing revealed by genetic axonal
      labeling of transient receptor potential melastatin 8 neurons.
AB  - Sensory nerves detect an extensive array of somatosensory stimuli, including
      environmental temperatures. Despite activating only a small cohort of sensory
      neurons, cold temperatures generate a variety of distinct sensations that range
      from pleasantly cool to painfully aching, prickling, and burning. Psychophysical
      and functional data show that cold responses are mediated by both C- and A delta
      fibers with separate peripheral receptive zones, each of which likely provides
      one or more of these distinct cold sensations. With this diversity in the neural
      basis for cold, it is remarkable that the majority of cold responses in vivo are
      dependent on the cold and menthol receptor transient receptor potential
      melastatin 8 (TRPM8). TRPM8-null mice are deficient in temperature
      discrimination, detection of noxious cold temperatures, injury-evoked
      hypersensitivity to cold, and nocifensive responses to cooling compounds. To
      determine how TRPM8 plays such a critical yet diverse role in cold signaling, we
      generated mice expressing a genetically encoded axonal tracer in TRPM8 neurons.
      Based on tracer expression, we show that TRPM8 neurons bear the neurochemical
      hallmarks of both C- and A delta-fibers, and presumptive nociceptors and non
      nociceptors. More strikingly, TRPM8 axons diffusely innervate the skin and oral
      cavity, terminating in peripheral zones that contain nerve endings mediating
      distinct perceptions of innocuous cool, noxious cold, and first- and second-cold
      pain. These results further demonstrate that the peripheral neural circuitry of
      cold sensing is cellularly and anatomically complex, yet suggests that cold
      fibers, caused by the diverse neuronal context of TRPM8 expression, use a single
      molecular sensor to convey a wide range of cold sensations.

PMID- 18094256
TI  - Differential trafficking of AMPA and NMDA receptors during long-term potentiation
      in awake adult animals.
AB  - Despite a wealth of evidence in vitro that AMPA receptors are inserted into the
      postsynaptic membrane during long-term potentiation (LTP), it remains unclear
      whether this occurs in vivo at physiological concentrations of receptors. To
      address the issue of whether native AMPA or NMDA receptors undergo such
      trafficking during LTP in the adult brain, we examined the synaptic and surface
      expression of glutamate receptor subunits during the early induction phase of LTP
      in the dentate gyrus of awake adult rats. Induction of LTP was accompanied by a
      rapid NMDA receptor-dependent increase in surface expression of glutamate
      receptor 1-3 (GluR1-3) subunits. However, in the postsynaptic density fraction
      only GluR1 accumulated. GluR2/3-containing AMPA receptors, in contrast, were
      targeted exclusively to extrasynaptic sites in a protein synthesis-dependent
      manner. NMDA receptor subunits exhibited a delayed accumulation, both at the
      membrane surface and in postsynaptic densities, that was dependent on protein
      synthesis. These data suggest that trafficking of native GluR1-containing AMPA
      receptors to synapses is important for early-phase LTP in awake adult animals,
      and that this increase is followed homeostatically by a protein synthesis
      dependent trafficking of NMDA receptors.

PMID- 18094257
TI  - Repeated electrical stimulation of reward-related brain regions affects cocaine
      but not "natural" reinforcement.
AB  - Drug addiction is associated with long-lasting neuronal adaptations including
      alterations in dopamine and glutamate receptors in the brain reward system.
      Treatment strategies for cocaine addiction and especially the prevention of
      craving and relapse are limited, and their effectiveness is still questionable.
      We hypothesized that repeated stimulation of the brain reward system can induce
      localized neuronal adaptations that may either potentiate or reduce addictive
      behaviors. The present study was designed to test how repeated interference with
      the brain reward system using localized electrical stimulation of the medial
      forebrain bundle at the lateral hypothalamus (LH) or the prefrontal cortex (PFC)
      affects cocaine addiction-associated behaviors and some of the neuronal
      adaptations induced by repeated exposure to cocaine. Repeated high-frequency
      stimulation in either site influenced cocaine, but not sucrose reward-related
      behaviors. Stimulation of the LH reduced cue-induced seeking behavior, whereas
      stimulation of the PFC reduced both cocaine-seeking behavior and the motivation
      for its consumption. The behavioral findings were accompanied by glutamate
      receptor subtype alterations in the nucleus accumbens and the ventral tegmental
      area, both key structures of the reward system. It is therefore suggested that
      repeated electrical stimulation of the PFC can become a novel strategy for
      treating addiction.

PMID- 18094258
TI  - The impact of catechol-O-methyltransferase and dopamine D4 receptor genotypes on
      neurophysiological markers of performance monitoring.
AB  - Dynamic adaptations of one's behavior by means of performance monitoring are a
      central function of the human executive system, that underlies considerable
      interindividual variation. Converging evidence from electrophysiological and
      neuroimaging studies in both animals and humans hints at the importance of the
      dopaminergic system for the regulation of performance monitoring. Here, we
      studied the impact of two polymorphisms affecting dopaminergic functioning in the
      prefrontal cortex [catechol-O-methyltransferase (COMT) Val108/158Met and dopamine
      D4 receptor (DRD4) single-nucleotide polymorphism (SNP)-521] on
      neurophysiological correlates of performance monitoring. We applied a modified
      version of a standard flanker task with an embedded stop-signal task to tap into
      the different functions involved, particularly error monitoring, conflict
      detection and inhibitory processes. Participants homozygous for the DRD4 T allele
      produced an increased error-related negativity after both choice errors and
      failed inhibitions compared with C-homozygotes. This was associated with
      pronounced compensatory behavior reflected in higher post-error slowing. No group
      differences were seen in the incompatibility N2, suggesting distinct effects of
      the DRD4 polymorphism on error monitoring processes. Additionally, participants
      homozygous for the COMT Val allele, with a thereby diminished prefrontal
      dopaminergic level, revealed increased prefrontal processing related to
      inhibitory functions, reflected in the enhanced stop-signal-related components N2
      and P3a. The results extend previous findings from mainly behavioral and
      neuroimaging data on the relationship between dopaminergic genes and executive
      functions and present possible underlying mechanisms for the previously suggested
      association between these dopaminergic polymorphisms and psychiatric disorders as
      schizophrenia or attention deficit hyperactivity disorder.

PMID- 18094259
TI  - Gbeta5 is required for normal light responses and morphology of retinal ON
      bipolar cells.
AB  - Gbeta5 exists as two splice variants, Gbeta5-S and Gbeta5-L, which interact with
      and stabilize the R7 members of the regulators of G-protein signaling (RGSs):
      RGS6, RGS7, RGS9, and RGS11. Although the role of Gbeta5-L and RGS9-1 is
      established in photoreceptors, the physiological functions of Gbeta5-S and other
      R7 RGS proteins remain unclear. We found that the electroretinogram of Gbeta5-/-
      mice lacks the b-wave component and that Gbeta5-S and RGS11 colocalize with Go
      alpha at the tips of the ON-bipolar cell dendrites. Unexpectedly, we found a
      significant reduction in the number of synaptic triads in the outer plexiform
      layer (OPL) of the Gbeta5-/- mice, which is evident at postnatal day 14.
      Transgenic expression of Gbeta5-L in rods failed to rescue the b-wave or the OPL
      defects. These results indicate that Gbeta5-S is indispensable for OPL integrity
      and normal light responses of the retina.

PMID- 18094260
TI  - The EphA4 receptor regulates neuronal morphology through SPAR-mediated
      inactivation of Rap GTPases.
AB  - Eph receptors play critical roles in the establishment and remodeling of neuronal
      connections, but the signaling pathways involved are not fully understood. We
      have identified a novel interaction between the C terminus of the EphA4 receptor
      and the PDZ domain of the GTPase-activating protein spine-associated RapGAP
      (SPAR). In neuronal cells, this binding mediates EphA4-dependent inactivation of
      the closely related GTPases Rap1 and Rap2, which have recently been implicated in
      the regulation of dendritic spine morphology and synaptic plasticity. We show
      that SPAR-mediated inactivation of Rap1, but not Rap2, is critical for ephrin-A
      dependent growth cone collapse in hippocampal neurons and decreased integrin
      mediated adhesion in neuronal cells. Distinctive effects of constitutively active
      Rap1 and Rap2 on the morphology of growth cones and dendritic spines support the
      idea that these two GTPases have different functions in neurons. Together, our
      data implicate SPAR as an important signaling intermediate that links the EphA4
      receptor with Rap GTPase function in the regulation of neuronal morphology.

PMID- 18094262
TI  - Do anticholinergic agents suppress uterine peristalsis and sporadic myometrial
      contractions at cine MR imaging?
AB  - PURPOSE: To prospectively evaluate anticholinergic drug effects on uterine
      peristalsis and sporadic myometrial contractions, as well as on intestinal
      motion, with cine magnetic resonance (MR) imaging. MATERIALS AND METHODS: This
      prospective study was approved by the institutional review board; informed
      consent was obtained from all participants. Twenty-one women (mean age, 29.3
      years +/- 4.0 [standard deviation]) underwent MR imaging during the follicular
      through periovulatory phases (cycle days 5-26). Before and after injection of an
      anticholinergic agent, 60 serial half-Fourier rapid acquisition with relaxation
      enhancement MR images were obtained within 2 minutes in the midsagittal uterine
      plane. Evaluations were performed independently and separately in random order by
      two radiologists who were blinded to whether an anticholingeric agent had been
      administered. Uterine peristalsis was evaluated for frequency (paired t test),
      predominant direction (McNemar test), degree of endometrial movement, wave
      conduction in the junctional zone (JZ), and wave conduction toward the outer
      myometrium (Wilcoxon signed rank test). Degree of sporadic contractions in the
      outer myometrium and intestinal motion were also evaluated (Wilcoxon signed rank
      test). RESULTS: On postinjection images, uterine peristalsis decreased in
      frequency from 4.57 waves per 2 minutes +/- 1.62 to 3.52 waves per 2 minutes +/-
      1.59, which is a 23% (95% confidence interval: 8.7%, 37.2%) average reduction (P
      = .003). There was no significant difference in actual predominant uterine
      peristalsis direction between pre- and postinjection images (P > .99). Although
      there were trends toward reduction of the degree of endometrial movement and of
      wave conduction in the JZ and toward the outer myometrium, these were not
      significant. The degree of sporadic myometrial contractions (P = .001) and
      intestinal motion (P < .001) decreased on postinjection images. CONCLUSION:
      Anticholinergic agents significantly suppress sporadic myometrial contractions
      and uterine peristalsis, in addition to intestinal motion, all of which may
      contribute to improved quality of conventional uterine MR images.

PMID- 18094261
TI  - Vigorous motor activity in Caenorhabditis elegans requires efficient clearance of
      dopamine mediated by synaptic localization of the dopamine transporter DAT-1.
AB  - The catecholamine dopamine (DA) functions as a powerful modulatory
      neurotransmitter in both invertebrates and vertebrates. As in man, DA neurons in
      the nematode Caenorhabditis elegans express a cocaine-sensitive transporter (DAT
      1), presumably to regulate synaptic DA signaling and limit DA spillover to
      extrasynaptic sites, although evidence supporting this is currently lacking. In
      this report, we describe and validate a novel and readily quantifiable phenotype,
      swimming-induced paralysis (SWIP) that emerges in DAT-1-deficient nematodes when
      animals exert maximal physical activity in water. We verify the dependence of
      SWIP on DA biosynthesis, vesicular packaging, synaptic release, and on the DA
      receptor DOP-3. Using DAT-1 specific antibodies and GFP::DAT-1 fusions, we
      demonstrate a synaptic enrichment of DAT-1 that is achieved independently of
      synaptic targeting of the vesicular monoamine transporter (VMAT). Importantly,
      dat-1 deletions and point mutations that disrupt DA uptake in cultured C. elegans
      neurons and/or impact DAT-1 synaptic localization in vivo generate SWIP. SWIP
      assays, along with in vivo imaging of wild-type and mutant GFP::DAT-1 fusions
      identify a distal COOH terminal segment of the transporter as essential for
      efficient somatic export, synaptic localization and in vivo DA clearance. Our
      studies provide the first description of behavioral perturbations arising from
      altered trafficking of DATs in vivo in any organism and support a model whereby
      endogenous DA actions in C. elegans are tightly regulated by synaptic DAT-1.

PMID- 18094263
TI  - CT colonography: investigation of the optimum reader paradigm by using computer
      aided detection software.
AB  - PURPOSE: To prospectively compare the diagnostic performance and time efficiency
      of both second and concurrent computer-aided detection (CAD) reading paradigms
      for retrospectively obtained computed tomographic (CT) colonography data sets by
      using consensus reading (three radiologists) of colonoscopic findings as a
      reference standard. MATERIALS AND METHODS: Ethical permission, HIPAA compliance
      (for U.S. institutions), and patient consent were obtained from all institutions
      for use of CT colonography data sets in this study. Ten radiologists each read 25
      CT colonography data sets (12 men, 13 women; mean age, 61 years) containing 69
      polyps (28 were 1-5 mm, 41 were >or=6 mm) by using workstations integrated with
      CAD software. Reading was randomized to either "second read" CAD (applied only
      after initial unassisted assessment) or "concurrent read" CAD (applied at the
      start of assessment). Data sets were reread 6 weeks later by using the opposing
      paradigm. Polyp sensitivity and reading times were compared by using multilevel
      logistic and linear regression, respectively. Receiver operating characteristic
      (ROC) curves were generated. RESULTS: Compared with the unassisted read, odds of
      improved polyp (>or=6 mm) detection were 1.5 (95% confidence interval [CI]: 1.0,
      2.2) and 1.3 (95% CI: 0.9, 1.9) by using CAD as second and concurrent reader,
      respectively. Detection odds by using CAD concurrently were 0.87 (95% CI: 0.59,
      1.3) and 0.76 (95% CI: 0.57, 1.01) those of second read CAD, excluding and
      including polyps 1-5 mm, respectively. The concurrent read took 2.9 minutes (95%
      CI: -3.8, -1.9) less than did second read. The mean areas under the ROC curve
      (95% CI) for the unassisted read, second read CAD, and concurrent read CAD were
      0.83 (95% CI: 0.78, 0.87), 0.86 (95% CI: 0.82, 0.90), and 0.88 (95% CI: 0.83,
      0.92), respectively. CONCLUSION: CAD is more time efficient when used
      concurrently than when used as a second reader, with similar sensitivity for
      polyps 6 mm or larger. However, use of second read CAD maximizes sensitivity,
      particularly for smaller lesions.

PMID- 18094265
TI  - Colorectal carcinoma: in vitro evaluation with high-spatial-resolution 3D
      constructive interference in steady-state MR imaging.
AB  - PURPOSE: To retrospectively assess the accuracy of high-spatial-resolution three
      dimensional (3D) constructive interference in steady-state (CISS) magnetic
      resonance (MR) imaging in the evaluation of mural invasion of colorectal
      carcinoma by using prospectively obtained in vitro images, with histopathologic
      analysis as the reference standard. MATERIALS AND METHODS: Institutional review
      board approval was obtained for the prospective and retrospective components of
      this study, with informed consent for the former and waiver of informed consent
      for the latter. Surgical specimens were obtained in 92 patients (61 men, 31
      women; mean age, 65 years) and contained 96 colorectal carcinomas. Specimens were
      examined with a 1.5-T MR system and a 4-cm-diameter loop coil. High-spatial
      resolution 3D CISS MR images were obtained with 80 x 80-mm field of view, 512 x
      512 matrix, and 0.7-mm section thickness, which resulted in a 0.017-mm(3) voxel
      size. The 3D data sets were postprocessed with surface-rendering software to
      generate virtual MR endoscopic images. The 3D CISS MR images were compared with
      histopathologic findings, and virtual MR endoscopic images were compared with
      macroscopic findings at surgery. Statistical analysis was performed with Spearman
      rank correlation. RESULTS: In 92 (96%) colorectal carcinomas, the depth of mural
      invasion depicted by 3D CISS MR imaging correlated well with the histopathologic
      stage, although the stage assigned with 3D CISS MR imaging was higher than that
      assigned with histopathologic analysis in four (4%) carcinomas (r = 0.976, P <
      .001). Sensitivity, specificity, and accuracy were 100%, 94%-96%, and 98%-100%,
      respectively. In 91 (95%) carcinomas, virtual MR endoscopy clearly depicted the
      macroscopic type of carcinoma, including gross configuration and tumor ulceration
      (r = 0.916, P < .001). CONCLUSION: High-spatial-resolution 3D CISS MR imaging has
      high diagnostic accuracy in the in vitro evaluation of mural invasion and
      macroscopic features of colorectal carcinomas.

PMID- 18094264
TI  - CT histogram analysis: differentiation of angiomyolipoma without visible fat from
      renal cell carcinoma at CT imaging.
AB  - PURPOSE: To retrospectively evaluate the diagnostic performance of computed
      tomographic (CT) histogram analysis for differentiating angiomyolipoma (AML)
      without visible fat from renal cell carcinoma (RCC) at CT, by using pathologic
      analysis and clinical diagnosis as the reference standard. MATERIALS AND METHODS:
      This retrospective study was approved by the institutional review board; informed
      consent was waived. The authors reviewed the medical records of 144 patients with
      pathologic confirmation of RCC or AML (105 men, 39 women; mean age, 52 years).
      Analysis of unenhanced CT histograms was performed on 34 AMLs without visible fat
      at CT and 110 size-matched RCCs. The percentages of voxels and pixels were
      compared in the two groups according to the CT number categories. The diagnostic
      performance of CT histogram analysis in differentiating AML from RCC was
      determined by using receiver operating characteristic (ROC) analysis. RESULTS:
      The percentages of voxels and pixels with a CT number less than -30 HU (2.7% and
      3.4% vs 0.1% and 0.0%), less than -20 HU (4.3% and 5.1% vs 0.2% and 0.1%), less
      than -10 HU (7.0% and 8.1% vs 0.6% and 0.4%), and less than 0 HU (12.0% and 13.9%
      vs 2.0% and 2.0%) were significantly greater in the AML group than in the RCC
      group (P < .01), respectively. The area under the ROC curve was as high as 0.706
      when a pixel percentage with a CT number less than -10 HU was used as a
      differentiating parameter. Corresponding to the specificity of 100% for
      differentiating AML from RCC, the sensitivity was as high as 20% when a pixel
      percentage of 6% with a CT number less than -10 HU was used as a criterion.
      CONCLUSION: CT histogram analysis may be useful for differentiating AML without
      visible fat from RCC at CT.

PMID- 18094266
TI  - MRI of acute bone bruises: timing of the appearance of findings in a swine model.
AB  - OBJECTIVE: We developed an animal model of bone injury to determine the timing of
      the MR appearance of bone bruises and to follow these changes over time.
      MATERIALS AND METHODS: We performed serial MRI of 16 knees of eight swine with
      one nontraumatized knee as a control and 15 knees traumatized by direct patellar
      impact injuries using a force-calibrated device. All knees were imaged on a 1.5-T
      scanner using an 8-channel phased-array coil with T1-weighted, fat-saturated T2
      weighted and STIR sequences. Scanning was performed at 1, 6, 12, and 30 hours
      after impact injury. Two radiologists independently reviewed each MR examination
      to identify MR signal intensity changes in the patellae and adjacent femoral
      condyles. RESULTS: In the 15 traumatized knees, bone bruises were noted in 93% of
      the patellae on T1-weighted images and in 87% of the patellae on fluid-sensitive
      MR images at 1 hour after injury and in 100% of the patellae at 6 hours. T1
      weighted images were insensitive for detection of bone bruises in the femoral
      condyles. Bone bruises in the femoral condyles were seen on fluid-sensitive MR
      sequences as early as 1 hour after injury, with an increasing frequency over the
      30-hour period. CONCLUSION: Bone bruises can be seen as soon as 1 hour after
      trauma but may not be seen until 30 hours after trauma. Fluid-sensitive (fat
      saturated, T2-weighted, and STIR) MR sequences are more sensitive than T1
      weighted images in the detection of bone bruises.

PMID- 18094267
TI  - Detection of early enhancement of hypervascular hepatocellular carcinoma using
      single breath-hold 3D pixel shift dynamic subtraction MDCT.
AB  - OBJECTIVE: The objective of our study was to evaluate the effect of single breath
      hold dynamic subtraction MDCT of the liver on the performance of radiologists in
      detecting focal enhancement during the hepatic arterial phase. SUBJECTS AND
      METHODS: This prospective study included 40 patients: 22 had hypervascular
      hepatocellular carcinoma (HCC), and 18 were without liver tumors. We obtained
      four-phase contrast-enhanced scans using a 16-MDCT unit. The section thickness
      and interval were 2 and 0.5 mm, respectively. Scanning for the first through
      fourth scans was started 10, 35, 70, and 180 seconds after the inception of
      contrast injection, respectively. Scanning for the first and second phase was
      within a single breath-hold. We subtracted the first-phase images from the second
      phase images using software developed in-house. We used receiver operating
      characteristic (ROC) analysis with a continuous rating scale from 1 to 100 to
      compare observer performance in the detection of focal enhancement on second
      phase images. Eight radiologists participated in the observer performance test,
      and their performances with unenhanced and contrast-enhanced original images were
      compared with their performances using contrast-enhanced subtracted images.
      RESULTS: For the eight observers, the mean area under the best-fit ROC curve
      (A(z)) values without and with the subtracted images were 0.86 +/- 0.05 (SD) and
      0.91 +/- 0.03, respectively. The difference was significant (p < 0.01, two-tailed
      paired Student's t test). CONCLUSION: The display of subtracted images
      significantly improved the diagnostic performance of radiologists in the
      detection of focal enhancement during the hepatic arterial phase (p < 0.01).

PMID- 18094268
TI  - Comparison of three free-breathing T2-weighted MRI sequences in the evaluation of
      focal liver lesions.
AB  - OBJECTIVE: The purpose of this study was to compare three free-breathing T2
      weighted MRI sequences in the evaluation of focal liver lesions. MATERIALS AND
      METHODS: Forty-nine patients with 86 focal liver lesions (56 malignant, 30
      benign) underwent liver MRI with free-breathing sequences: turbo spin-echo (TSE)
      with navigator-triggered prospective acquisition correction (PACE), respiration
      triggered TSE, and HASTE with navigator-triggered PACE. The images were
      retrospectively reviewed by two independent observers. Diagnostic performance was
      evaluated with receiver operating characteristics and sensitivity. The images
      were assessed quantitatively by measurement of the liver signal-to-noise ratio
      (SNR) and the lesion-to-liver contrast-to-noise ratio (CNR). RESULTS: The PACE
      TSE sequence had better receiver operating characteristic curves for lesion
      detection and characterization than did the respiration-triggered TSE sequence,
      but the difference was not statistically significant (p > 0.05). The PACE TSE
      sequence had a significantly greater area under the curve for lesion detection (p
      < 0.01) and lesion characterization (p < 0.001) than did the PACE HASTE sequence.
      The composite sensitivity of the PACE TSE sequence for lesion detection was
      significantly higher than that of respiration-triggered TSE (p < 0.05) and PACE
      HASTE (p < 0.01). The mean signal-to-noise ratio for liver and the contrast-to
      noise ratio for hepatic lesions were higher with the PACE HASTE than with the
      other sequences. CONCLUSION: The navigator-triggered PACE technique is a valid
      method for T2-weighted MRI of the liver and may replace conventional respiration
      triggered techniques.

PMID- 18094269
TI  - Arterial blood supply of hepatocellular carcinoma and histologic grading:
      radiologic-pathologic correlation.
AB  - OBJECTIVE: The objective of our study was to clarify the sequential changes of
      arterial blood supply during the development of hepatocellular carcinoma (HCC)
      with an emphasis on its late stage. MATERIALS AND METHODS: Sixty HCC nodules were
      confirmed at pathology in 59 patients who had undergone CT hepatic arteriography
      and CT during arterioportography (CTAP). Lesions were classified into one of the
      four groups: group 1, nodules that appeared to show preserved portal perfusion on
      CTAP and showed hypo- or isoattenuation on CT hepatic arteriography; group 2,
      very hyperattenuating on CT hepatic arteriography; group 3, hyperattenuating on
      CT hepatic arteriography; and group 4, hypo- or isoattenuating on CT hepatic
      arteriography. Groups 2, 3, and 4 showed the portal perfusion defect on CTAP.
      These hemodynamic patterns were compared among different histologic grades. We
      also examined the number of unpaired arteries and the Ki-67 labeling index of the
      tumor pathologically. RESULTS: The numbers of lesions in each group were as
      follows for groups 1, 2, 3, and 4, respectively: 17, one, two, and 0 well
      differentiated HCCs; 0, 10, nine, and one moderately differentiated HCC; and 0,
      three, 12, and five poorly differentiated HCCs. The lesions showed significantly
      different hemodynamic patterns among different histologic grades (Cramer's V =
      0.6919, p < 0.0001). The number of unpaired arteries showed a strong correlation
      with Ki-67 labeling index in well-differentiated HCC and moderately
      differentiated HCC (rho = 0.673, p < 0.0001) and a moderate inverse correlation
      with Ki-67 labeling index in poorly differentiated HCC (rho = -0.540, p =
      0.0185). CONCLUSION: In the late stage of HCC development, the arterial blood
      supply significantly decreases as the histologic grade progresses.

PMID- 18094270
TI  - Arteriovenous fistulas of the facial artery after mandibular surgery: treatment
      by embolization.
AB  - OBJECTIVE: We describe three cases of arteriovenous fistula (AVF) that developed
      between the facial artery and facial vein after mandibular surgery, two after
      sagittal split osteotomy of the mandible and one after the removal of an infected
      dental bridge, and discuss the embolization techniques that were used for their
      successful treatment. CONCLUSION: AVF between the facial artery and vein can be
      successfully treated by embolization and is usually best achieved by occluding
      the facial artery on both sides of the arterial injury.

PMID- 18094271
TI  - MDCTA of carotid plaque degree of stenosis: evaluation of interobserver
      agreement.
AB  - OBJECTIVE: Atherosclerotic disease of the carotid arteries is one of the most
      important causes of stroke. Our objective was to evaluate the interobserver
      agreement in the measurement of the degree of carotid plaque stenosis by using
      MDCT angiography (MDCTA) and the effects produced using different window
      parameters and by the different types of plaque. MATERIALS AND METHODS: From June
      2005 to June 2006, we retrospectively evaluated 215 patients (151 men, 64 women)
      who underwent MDCTA for the study of carotid arteries. In all patients we
      measured degree of stenosis, applying the criteria of the North American
      Symptomatic Carotid Endarterectomy Trial (NASCET). Each patient was studied
      independently by two observers. We used three window settings for the
      measurements. We grouped the measurements according to the type of plaque.
      Obtained data were then analyzed to calculate the interobserver agreement and the
      kappa value. RESULTS: Kappa values for the degree of stenosis evaluation were
      0.696, 0.79, and 0.775 for window settings 1, 2, and 3, respectively. The best
      agreement was observed in the assessment of fatty plaque, whereas the presence of
      calcification produced disagreement. CONCLUSION: We observed a very good
      interobserver agreement in the evaluation of degree of stenosis using MDCTA with
      the application of specific visualization parameters. Our data suggested that
      MDCTA can provide reproducible values.

PMID- 18094272
TI  - Contrast enhancement in cardiac MDCT: comparison of iodixanol 320 versus iohexol
      350.
AB  - OBJECTIVE: The objective of our study was to evaluate whether iodixanol 320 mg
      I/mL (iodixanol 320), with the highest iodine concentration of dimeric nonionic
      contrast agents on the market, results in decreased vascular or myocardial
      enhancement compared with iohexol 350 mg I/mL (iohexol 350). SUBJECTS AND
      METHODS: During a 4-month period, 72 patients referred for cardiac MDCT were
      consecutively enrolled and randomized into two groups: iohexol 350 and iodixanol
      320. The injection and scanning protocols were the same for both groups.
      Enhancement of the right heart, left heart, coronary arteries, and left
      ventricular (LV) myocardium in both the arterial and delayed phases was compared
      using two-tailed independent Student's t test. RESULTS: Enhancement in the right
      heart, left heart, coronary arteries, and LV myocardium in the arterial phase
      showed no statistical difference (p > 0.05) between the two groups, although the
      iohexol group showed slightly higher enhancement (average, 11.2 H) in all of the
      areas. Surprisingly, in the delayed phase, the iodixanol group displayed
      significantly higher (7.7 H) persistent enhancement (p < 0.05) in the LV
      myocardium. CONCLUSION: Iodixanol 320 can provide vascular enhancement in cardiac
      MDCT that is similar to iohexol 350. In the delayed phase, iodixanol 320 shows
      significantly higher delayed enhancement (7.7 H) in the LV myocardium than
      iohexol 350.

PMID- 18094273
TI  - Pediatric chest MDCT using tube current modulation: effect on radiation dose with
      breast shielding.
AB  - OBJECTIVE: The purpose of our study was to assess the effect on radiation dose
      and image noise during pediatric chest 16-MDCT using automatic tube current
      modulation and bismuth breast shields. MATERIALS AND METHODS: Age-based chest 16
      MDCT was performed on an anthropomorphic phantom representing a 5-year-old child.
      Two scans were obtained in each of four sequences: first, without a shield;
      second, with a 2-ply bismuth shield; third, using automatic tube current
      modulation with a scout image obtained after placement of the shield; and fourth,
      using automatic tube current modulation with a scout image obtained before
      placement of the shield. Metal oxide semiconductor field effect transistor
      technology was used to measure the radiation dose in 20 organ locations.
      Effective dose was estimated using the console dose-length product. Noise was
      measured by recording the SD of Hounsfield units in identical regions of
      interest. RESULTS: The bismuth breast shield reduced the dose to the breast by
      26%. Shielding and automatic tube current modulation reduced the breast dose by
      52%. Multiple organ doses were lowest when the shield was placed after the scout
      radiograph had been obtained. When the shield was placed after the scout image
      was obtained, the mean noise in the range of shielding increased from 11.4 to
      13.1 H (superior mediastinum) and from 10.0 to 12.8 H (heart) (p < 0.01).
      Increased noise, however, was near the target noise index (measured in SD of
      Hounsfield units) of 12.0 H (SD). Using automatic tube current modulation, the
      effective dose was reduced by 35% when the shield was placed after the scout and
      by 20% when the shield was present in the scout. CONCLUSION: The greatest dose
      reduction is achieved by placing the shield after obtaining the scout image to
      avoid Auto mA compensation due to density of shield. With this technique, image
      noise increased but remained close to the target noise index.

PMID- 18094274
TI  - A diagnostic pitfall for intracranial aneurysms in time-of-flight MR angiography:
      small intracranial lipomas.
AB  - OBJECTIVE: The sensitivity of MR angiography (MRA) for aneurysms smaller than 3
      mm in diameter is limited. Diagnostic pitfalls may arise from primary T1
      hyperintense lesions on time-of-flight (TOF) imaging adjacent to a vessel.
      Independently, three patients were referred from outside facilities for
      diagnostic workup of suspected aneurysms of the vertebrobasilar system on TOF
      images. The lesions were identified as small lipomas, which prompted us to
      systematically analyze characteristics of intracranial lipomas on TOF images.
      MATERIALS AND METHODS: From our local database, 38,000 cranial MRI scans were
      searched for intracranial lipomas. If available, TOF images of identified lipomas
      were analyzed. In addition, in vitro MRI of excised cadaveric lipomas and other
      fatty specimens were examined for characteristics on TOF images and the presence
      of chemical shift artifacts. RESULTS: Seventeen intracranial lipomas (0.045%)
      were identified. Out-of-phase TOF source images available in 12 identified
      lipomas showed a continuous dark peripheral fringe and a hyperintense center. In
      vitro out-of-phase chemical shift images of excised cadaveric lipomas revealed
      the same consistent fringe artifact, known as "india ink," independent of size,
      shape, surrounding fibrous capsule, or texture of the fatty specimen. In
      contrast, in-phase chemical shift artifact was variable. CONCLUSION: Small
      intracranial lipomas close to a cerebral artery are hyperintense on TOF MR images
      and could be mistaken for partially thrombosed aneurysms and associated flow
      related artifact. A defining characteristic of lipomas on TOF source images
      results from the out-of-phase india ink artifact. This dark fringe in the
      periphery of the lesions is characteristic and helps avoid potential diagnostic
      pitfalls.

PMID- 18094275
TI  - Freeware program for converting image sequences to Flash movie loops.
AB  - OBJECTIVE: This article provides a freeware program created for converting image
      sequences to Flash movie loops. CONCLUSION: Although Flash is a useful format for
      presenting dynamic data sets in PowerPoint compared with other movie clip formats
      (e.g., AVI), the associated cost of the required Flash application ($699) is a
      common concern for many academic radiologists. To address this issue, a freeware
      program for creating simple Flash movie loops from image sequences has been
      developed for this article.

PMID- 18094276
TI  - Fibrosing colonopathy in adults with cystic fibrosis.

PMID- 18094277
TI  - Sonographic appearance of the epididymis in pediatric testicular torsion.

PMID- 18094278
TI  - MRI and the detection of bone marrow tumor.

PMID- 18094279
TI  - Citing web articles.

PMID- 18094280
TI  - Pituitary duplication or suprasellar encephalocele?

PMID- 18094281
TI  - An old memory.

PMID- 18094282
TI  - Three-point technique of fat quantification of muscle tissue as a marker of
      disease progression in Duchenne muscular dystrophy: preliminary study.
AB  - OBJECTIVE: Clinical trials involving patients with Duchenne muscular dystrophy
      are hindered by the lack of suitable objective end points. The purpose of this
      study was to examine whether muscle lipid infiltration measured with the three
      point Dixon MRI technique has value as a marker of disease severity. SUBJECTS AND
      METHODS: Disease severity in nine boys (mean age, 8.6 +/- 2.7 years) with
      Duchenne muscular dystrophy was determined with the functional ability scale of
      Brooke and associates. Functional scores were compared with strength measurements
      obtained by manual testing of muscles of the lower extremities, knee extensor
      strength measured with an isokinetic dynamometer, and muscle fat percentage in
      the quadriceps and hamstrings determined with the three-point Dixon MRI
      technique. RESULTS: MRI measurements of fat infiltration had stronger correlation
      (p < 0.05) with functional grade than did measurements obtained with manual
      muscle testing (p = 0.07) or quantitative strength measured with the isokinetic
      dynamometer (p = 0.54). Muscle fat percentage did not correlate with strength
      measurements from manual or dynamometer muscle testing but increased with age in
      subjects with Duchenne muscular dystrophy. CONCLUSION: Muscle adiposity values
      obtained with three-point Dixon MRI are accurate in assessment of disease
      severity in patients with Duchenne muscular dystrophy. Because they are not
      influenced by patient effort or examiner variability, these measurements are more
      objective and reproducible than measurements of muscle strength.

PMID- 18094283
TI  - Case reports: a premature demise.

PMID- 18094284
TI  - Role of the radiologist in the preoperative evaluation of primary
      hyperparathyroidism.

PMID- 18094285
TI  - New program requirements for diagnostic radiology: update and discussion of the
      more complex requirements.

PMID- 18094286
TI  - Musculoskeletal sonography technique: focused versus comprehensive evaluation.
AB  - OBJECTIVE: This article evaluates the utility of performing a focused
      musculoskeletal sonography examination on the basis of patients' presenting
      complaints. MATERIALS AND METHODS: Six hundred two patients evaluated over 6
      months were scanned using a routine protocol. At the completion of the routine
      examination, each patient was asked to indicate a focal point of discomfort and,
      if present, was rescanned over the area of discomfort. Patients were classified
      in one of five categories depending on whether there was a focal point of
      discomfort and the presence or absence of an underlying sonographic abnormality.
      RESULTS: Eighty-three percent of the 602 patients had a sonographically
      detectable abnormality, 2.2% of whom had an abnormality not detectable by routine
      protocol-based scanning. The more peripheral the body part, the more likely that
      abnormalities detected by sonography correlated with focal symptoms: 81% in the
      wrist and hand and 73% in the ankle and foot, compared with the more central body
      parts of 15% in the shoulder and 31% in the hip. Chi-square analysis showed a
      significant association between the body part scanned and a detectable
      abnormality (p < 0.0001). CONCLUSION: Although a focused examination of the
      distal extremities correlated with an abnormality in most cases, a protocol-based
      approach ensured identifying 97.4% of the symptomatic abnormalities. The addition
      of a focused examination to an examination by protocol further increased the
      identification of abnormalities.

PMID- 18094287
TI  - MDCT and radiography of wrist fractures: radiographic sensitivity and fracture
      patterns.
AB  - OBJECTIVE: The purpose of our study was to determine which wrist fractures are
      not prospectively diagnosed at radiography using CT as a gold standard and to
      identify specific fracture patterns. MATERIALS AND METHODS: Through a search of
      radiology records from January 1 to December 31, 2005, 103 consecutive patients
      were identified as having radiographic and CT examinations of the wrist. After
      excluding incomplete or nondiagnostic examinations and those with a greater than
      6-week interval between imaging studies, the final study group consisted of 61
      wrist examinations in 60 patients. Two musculoskeletal radiologists and one
      emergency radiologist blindly reviewed CT examinations, and each bone (scaphoid,
      lunate, triquetrum, pisiform, trapezium, trapezoid, capitate, hamate,
      metacarpals, distal radius, distal ulna) was categorized as normal or fractured,
      with agreement reached by consensus. Each prospective radiographic report was
      categorized as either normal or fracture/equivocal for each osseous structure.
      Results were compared using the chi-square and Fisher's exact tests. RESULTS: In
      the proximal carpal row, lunate and triquetrum fractures were often
      radiographically occult (0% and 20%, respectively, detected at radiography);
      whereas in the distal carpal row, trapezoid, capitate, and hamate fractures were
      often occult (0%, 0%, and 40% detected at radiography, respectively). Hamate
      fractures were significantly associated with metacarpal fractures, and distal
      radius fractures were associated with scaphoid and ulna fractures. CONCLUSION:
      Thirty percent of wrist fractures were not prospectively diagnosed on
      radiography, suggesting that CT should be considered after a negative
      radiographic finding if clinically warranted. The location of a dorsal scaphoid
      avulsion fracture emphasizes the need for specific radiographic views or cross
      sectional imaging for diagnosis.

PMID- 18094288
TI  - Prevalence and MRI-anatomic correlation of bone cysts in osteoarthritic knees.
AB  - OBJECTIVE: The objectives of this study were to determine the prevalence of cysts
      in the weight-bearing areas and interspinous bone cysts in tibial plateau
      specimens derived from knees with advanced osteoarthritis, to perform MRI
      anatomic correlation of these cysts, and to define their histologic
      characteristics. MATERIALS AND METHODS: Forty-two tibial plateau specimens were
      recovered from patients undergoing total knee replacement surgery for severe
      osteoarthritis (14 men and 28 women; mean age, 74 years; age range, 58-87 years).
      The tibial specimens underwent MRI with T1- and T2-weighted MR sequences. No
      radiographic data were available before MRI. Tibial specimens were sectioned
      using a high-speed rotating diamond disk into 3-mm-thick slices. MR images and
      anatomic specimens were analyzed for the presence of cysts in the interspinous
      and weight-bearing areas. Histologic staining methods included routine Harris
      hematoxylin stain, trichrome stain, and Alcian blue-PAS stain. RESULTS: Twenty
      three (54%) of 42 specimens contained one or more cystic areas, with a total of
      30 cystic areas. The cysts were distributed in the weight-bearing area (14/30)
      and interspinous area (16/30). All cysts seen on the anatomic slices could also
      be depicted on both MRI sequences. Histologic findings were identical for all
      noncommunicating cysts and revealed necrotic bone fragments with dead
      denuclearized cells. The cavities were surrounded by a layer of fibrous
      connective tissue containing adipocytes and osteoblasts. No evidence of
      epithelial components was found in the lining of the cavities. CONCLUSION:
      Interspinous and weight-bearing tibial cysts are common in severe knee
      osteoarthritis. The cysts contain necrotic bone fragments and are lined by a
      nonepithelial fibrous wall. Our findings support the hypothesis that interspinous
      cysts could result from repetitive bone stresses through the cruciate ligaments.
      Our findings do not support the use of the term "herniation cyst."

PMID- 18094289
TI  - Clinical, MRI, and arthroscopic findings associated with failure to diagnose a
      lateral meniscal tear on knee MRI.
AB  - OBJECTIVE: We performed this study to determine whether clinical, MRI, or
      arthroscopic findings are associated with missed lateral meniscal tears to help
      understand why these tears are missed on MRI. MATERIALS AND METHODS: We reviewed
      the medical records of 483 patients who had undergone knee MRI and arthroscopy.
      We assessed patient age; spontaneous or traumatic onset of knee pain; interval
      between pain onset and MRI; interval between MRI and arthroscopy; and
      arthroscopic type, size, and location of lateral meniscal tear for their
      association with a missed lateral meniscal tear. Each MR examination with a
      missed lateral meniscal tear was reviewed to determine whether the tear could be
      seen in retrospect. RESULTS: Thirty-six of the 189 lateral meniscal tears found
      at arthroscopy were not diagnosed on the original MR interpretations. There was a
      significant association between a missed lateral tear and a posterior horn tear
      or a tear involving only one third of the meniscus. There was no association
      between a missed lateral meniscal tear and the other variables. Review of the 36
      missed tears revealed that 10 tears were visible retrospectively, six of which
      were longitudinal peripheral tears in the posterior horn. CONCLUSION: Lateral
      meniscal tears are more likely to be missed if the tear involves only one third
      of the meniscus or is in the posterior horn. Longitudinal peripheral tears of the
      posterior horn were the most commonly missed tears that could be seen in
      retrospect.

PMID- 18094290
TI  - Does extended-field-of-view sonography improve interrater reliability for the
      detection of rotator cuff muscle atrophy?
AB  - OBJECTIVE: Assessment of rotator cuff muscle atrophy is an important component of
      the shoulder sonogram. We hypothesized that extended-field-of-view (EFOV)
      sonography would allow greater interrater reliability than conventional
      sonography for the evaluation of rotator cuff muscle atrophy. MATERIALS AND
      METHODS: This retrospective study involved 50 consecutive patients who presented
      for shoulder sonography. All patients underwent EFOV imaging of the supraspinatus
      and infraspinatus muscles in addition to conventional imaging of each muscle.
      Five musculoskeletal radiologists first assessed 50 EFOV images of the
      supraspinatus and infraspinatus muscles and scored both muscles using a scale of
      1-5. The reliability of each method was determined by calculating intraclass
      correlation coefficients (ICCs) according to a method developed by Shrout and
      Fleiss. The significance of the difference between reliabilities for conventional
      images and EFOV images was tested with a z-test. RESULTS: For the EFOV images,
      the ICC for the supraspinatus muscle was 0.77 and for the infraspinatus, 0.75.
      For the conventional images, the ICC for the supraspinatus muscle was 0.52 and
      for the infraspinatus, 0.57. The degree of interrater reliability for the five
      readers in our study was significantly higher for the EFOV images than for the
      conventional images (p < 0.0001). CONCLUSION: EFOV sonography results in greater
      interrater reliability than conventional sonography for the detection of rotator
      cuff muscle atrophy. EFOV images of the rotator cuff muscles should be obtained
      as part of routine shoulder sonography.

PMID- 18094291
TI  - MRI findings in deep and generalized morphea (localized scleroderma).
AB  - OBJECTIVE: Our objective was to describe the spectrum of MRI features in patients
      with deep and generalized morphea. CONCLUSION: Imaging features of morphea are
      not specific and usually overlap with those of other disorders involving the
      skin, fascia, and musculature, such as some types of fasciitis, myositis, and so
      forth. Nevertheless, the imaging features of morphea reflect pathomorphologic
      changes of this rare disorder and enable a complete assessment of the disease
      extent, including depth of infiltration and disease activity.

PMID- 18094292
TI  - Enchondroma protuberans of the hand.
AB  - OBJECTIVE: Enchondroma protuberans is a rare tumor that arises from an
      intramedullary enchondroma with an exophytic growth pattern. The purpose of this
      study was to describe imaging findings of this disease that were obtained using
      both radiography and MRI. CONCLUSION: It is necessary to understand the
      characteristic imaging findings of enchondroma protuberans to avoid misdiagnosis.
      When radiography does not allow a clear diagnosis of enchondroma protuberans, MRI
      may be helpful for diagnosis.

PMID- 18094293
TI  - Double-contrast MRI for accurate staging of hepatocellular carcinoma in patients
      with cirrhosis.
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of a double
      contrast MRI protocol in staging of hepatocellular carcinoma (HCC) in patients
      with cirrhosis. MATERIALS AND METHODS: This cross-sectional study was performed
      at a tertiary liver care center. Forty-eight patients with cirrhosis underwent
      double-contrast MRI for clinical care and liver transplantation. For each MRI
      examination, superparamagnetic iron oxide was infused, and 2D T2*-weighted
      spoiled gradient-recalled echo and T2-weighted echo-train spin-echo MR images
      were obtained for assessment of phagocytic function. Immediately afterward, a low
      molecular-weight gadolinium compound was injected, and 3D T1-weighted spoiled
      gradient-recalled echo images were acquired dynamically for assessment of
      vascularity. Two blinded radiologists independently reviewed all MR images and
      assigned per-lesion and per-patient cancer confidence scores to determine the
      American Liver Tumor Study Group tumor stage. The imaging-based cancer scores and
      tumor stages were correlated with pathology reports. Performance parameters were
      computed for imaging-based measurements. RESULTS: Of the 48 study subjects, 25
      had HCC (three, T1; 18, T2; one, T3; one, T4a; two, T4b). In total, there were 37
      HCC nodules. The accuracy of MRI in prediction of pathologic tumor stage was 81
      85% depending on the radiologist. Per-patient and per-lesion sensitivity in the
      diagnosis of HCC were 96% and 81% for one radiologist and 96% and 89% for the
      other. CONCLUSION: A double-contrast MRI protocol has high accuracy in staging of
      HCC in patients with cirrhosis.

PMID- 18094294
TI  - Focal nodular hyperplasia and hepatic adenoma: differentiation with low
      mechanical-index contrast-enhanced sonography.
AB  - OBJECTIVE: The purpose of our study was to determine the differentiating features
      of focal nodular hyperplasia (FNH) and hepatic adenoma on contrast-enhanced
      sonography. MATERIALS AND METHODS: Sixty-two patients who underwent contrast
      enhanced sonography and were confirmed to have FNH (n = 43) or hepatic adenoma (n
      = 19) were assessed retrospectively for arterial phase enhancement, filling
      direction, stellate arteries, and portal phase enhancement. An algorithm was
      applied to these interpreted features to determine the contrast-enhanced
      sonography diagnosis. RESULTS: All lesions were hypervascular in the arterial
      phase. Centrifugal filling was more common in FNH (39 and 32 of 43, 91% and 74%
      [reader 1 and reader 2]) than in adenoma (3 and 3 of 19, 16%). Centripetal or
      mixed filling was more common in adenoma (16 and 16 of 19, 84%) than in FNH (4
      and 11 of 43, 9% and 26%) (p < 0.001, kappa = 0.61). Stellate arteries
      characterized FNH (29 and 26 of 43, 67% and 60%) but not adenoma (3 and 2 of 19,
      16% and 11%) (p < 0.001, kappa = 0.36). Sustained portal phase enhancement was
      more common in FNH (37 and 39 of 43, 86% and 91%) than in adenoma (9 and 12 of
      19, 47% and 63%) (p < 0.02, kappa = 0.79). The sensitivity, specificity, positive
      predictive value, and negative predictive value of sonography for diagnosing FNH
      were 95% and 86%, 74% and 79%, 89% and 90%, and 88% and 71%, (reader 1 and reader
      2, respectively). CONCLUSION: FNH is predicted on the basis of arterial phase
      centrifugal filling and stellate vascularity on contrast-enhanced sonography.
      Adenoma is less reliably predicted on the basis of centripetal or mixed filling
      without stellate vascularity. Sustained portal phase enhancement is more common
      in FNH than in adenoma but contributes less to the differentiation of these
      lesions.

PMID- 18094295
TI  - Functional MRI evaluation of tumor response in patients with neuroendocrine
      hepatic metastasis treated with transcatheter arterial chemoembolization.
AB  - OBJECTIVE: The purpose of this study was to evaluate contrast-enhanced and
      diffusion-weighted MRI changes in neuroendocrine tumors treated with
      transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Sixty-six
      targeted lesions in 26 patients (18 men, eight women; mean age, 57 years) with
      hepatic metastasis of neuroendocrine tumors treated with TACE were
      retrospectively analyzed. MRI studies were performed before and after TACE.
      Imaging features included tumor size, percentage of enhancement in the arterial
      and portal venous phases, and diffusion-weighted imaging apparent diffusion
      coefficients (ADCs) of the tumor, liver, and spleen. Tumor response to treatment
      was recorded according to World Health Organization criteria and Response
      Evaluation Criteria in Solid Tumors. Liver function tests were performed, and
      clinical performance was assessed before and after treatment. Statistical
      analysis included paired Student's t tests and Kaplan-Meier survival curves.
      RESULTS: Mean tumor size and percentage enhancement in the arterial and portal
      venous phases decreased significantly after treatment (p < 0.0001). The tumor ADC
      increased from 1.51 x 10(-3) mm2/s before treatment to 1.79 x 10(-3) mm2/s after
      treatment (p < 0.0001), but the ADCs for the liver and spleen remained unchanged.
      Despite the change in tumor size, no patient in this cohort achieved complete
      response according to World Health Organization criteria and Response Evaluation
      Criteria in Solid Tumors. Partial response was achieved in only 27% and 23% of
      the patients according to the respective criteria. Results of liver function
      tests and performance status also remained unchanged. The mean survival period
      for all patients was 78 months. CONCLUSION: Contrast-enhanced and diffusion
      weighted imaging showed significant changes after TACE of neuroendocrine tumors
      and can be used to assess response of targeted tumors.

PMID- 18094296
TI  - Accuracy of preoperative T-staging of gallbladder carcinoma using MDCT.
AB  - OBJECTIVE: The objective of our study was to evaluate the performance of MDCT in
      the preoperative T-staging of gallbladder cancer and to determine whether adding
      multiplanar reconstruction (MPR) images to axial images can improve the accuracy
      of MDCT for the T-staging of gallbladder cancer. MATERIALS AND METHODS: Two
      abdominal radiologists retrospectively reviewed by consensus axial images of
      portal phase MDCT scans of 118 patients who had pathologically confirmed
      gallbladder cancers; they then reviewed the axial and MPR images from 53 of the
      118 patients who had undergone MPR imaging. Local disease spread was evaluated
      according to the TNM system, and the results were compared with the pathologic
      findings using the McNemar test. The MDCT performance to differentiate each T
      stage was evaluated using Fisher's exact test. RESULTS: The sensitivities of the
      ability to differentiate the < or = T1 versus > or = T2 lesions, < or = T2 versus
      > or = T3 lesions, and < or = T3 versus T4 lesions were 79.3%, 92.7%, and 100%,
      respectively; the specificities were 98.8%, 86%, and 100%, respectively (p <
      0.0001). The overall accuracy for the T-stage was 83.9%. In the 53 patients with
      MPR images, the combined reading of the axial and MPR images increased the
      diagnostic accuracy compared with axial image reading only from 71.7% to 84.9%, a
      statistically significant degree (p = 0.0233). CONCLUSION: MDCT provided 83.9%
      accuracy in the diagnosis of the local extent of gallbladder carcinomas, thereby
      showing acceptable sensitivity and specificity. The addition of MPR images to the
      axial CT data increased the accuracy.

PMID- 18094297
TI  - Radiologic detectability of minute portal venous invasion in hepatocellular
      carcinoma.
AB  - OBJECTIVE: The objective of this study was to evaluate whether minute portal
      venous invasion in hepatocellular carcinoma (HCC) can be diagnosed
      radiologically. MATERIALS AND METHODS: CT hepatic arteriography and CT with
      arterioportography (CTAP) of 15 patients with minute portal venous invasion
      (group 1) and 30 patients without it (group 0) were evaluated. An area showing
      low attenuation on CTAP and high attenuation on CT hepatic arteriography around
      the tumor was defined as an area of peritumoral hemodynamic change. The shape and
      size of the area were compared between the two groups. The ratio of the area of
      peritumoral hemodynamic change volume to tumor volume (area volume-tumor volume
      ratio) was used as an indicator of the size of the area of peritumoral
      hemodynamic change and was categorized as one of three grades: grade I, 10% or
      less; grade II, between 10% and 30%; and grade III, 30% or more. The
      detectability of minute portal invasion was assessed when grade III was
      considered as an indicator. Each comparison was also made independently when the
      tumor diameter either was limited to less than 3 cm or was 3 cm or more. RESULTS:
      Three types of area of peritumoral hemodynamic change were identified: wedge
      shaped, belt-shaped or irregular, and linear. No significant difference in the
      frequency of each type of area of peritumoral hemodynamic change was observed
      between the two groups. The area volume-tumor volume ratio in group 1 was larger
      than that in group 0, with statistical significance when the tumor diameter was
      less than 3 cm (p = 0.046). Positive and negative predictive values were 71.4%
      and 75.0%, respectively, when the tumor diameter was less than 3 cm. CONCLUSION:
      The area of peritumoral hemodynamic change in HCC patients with minute portal
      invasion (group 1) may be larger than in those without it (group 0), especially
      when tumors are small.

PMID- 18094298
TI  - Percutaneous radiofrequency ablation with artificial ascites for hepatocellular
      carcinoma in the hepatic dome: initial experience.
AB  - OBJECTIVE: Our objective was to assess the feasibility, safety, and efficacy of
      percutaneous radiofrequency ablation with artificial ascites for hepatocellular
      carcinoma (HCC) in the hepatic dome. MATERIALS AND METHODS: Sonographically
      guided percutaneous radiofrequency ablation with artificial ascites was performed
      in 25 patients with 34 HCCs using an internally cooled electrode radiofrequency
      system. At least one hepatic dome tumor in each patient was considered difficult
      to treat percutaneously because of partially visible tumor (n = 16) or poor
      electrode path (n = 9) on planning sonography. We artificially induced ascites
      before radiofrequency ablation by dripping 5% dextrose in water (D/W) solution to
      improve tumor visibility or electrode path and to separate the radiofrequency
      ablation zone from the diaphragm. We assessed the technical feasibility, safety,
      and efficacy of this technique with clinical and CT follow-up for at least 4
      months (mean, 281.4 days) RESULTS: Artificial ascites was successfully achieved
      in 22 (88%) of 25 patients with the administration of a mean of 348 mL of D/W
      solution for an additional mean time of 9.3 minutes. There was substantial
      improvement in the visibility in 93.4% (15/16) of the partially visible tumors
      and in achieving a better path in 77.8% (7/9) of the tumors with a poor electrode
      path. The primary technique effectiveness rate for hepatic dome tumors was 96%
      (24/25) at 1-month follow-up CT. There was no diaphragmatic thermal injury in all
      but one case. No complication related to artificial ascites occurred during the
      follow-up period. CONCLUSION: Percutaneous radiofrequency ablation with
      artificial ascites appears a feasible, safe, and effective technique for treating
      HCC of the hepatic dome.

PMID- 18094299
TI  - Hepatic arterial chemoembolization for management of metastatic melanoma.
AB  - OBJECTIVE: Hepatic arterial chemoembolization is an accepted therapy for stage 4
      melanoma with liver-dominant metastasis. However, the reports of outcomes are
      limited. We present our outcomes with hepatic arterial chemoembolization for
      metastasis of stage 4 melanoma. MATERIALS AND METHODS: Twenty patients with liver
      dominant metastasis of ocular or cutaneous melanoma were treated with hepatic
      arterial chemoembolization. Overall survival and progression-free survival rates
      were calculated from the first treatment. Patients with intrahepatic tumor
      progression were treated with additional hepatic arterial chemoembolization. Both
      overall survival and progression-free survival were analyzed with the Kaplan
      Meier method. Tumor pattern on angiography was characterized as either nodular or
      infiltrative on the basis of angiographic appearance. RESULTS: The 20 patients
      underwent 46 hepatic arterial chemoembolization sessions (mean, 2.4 sessions;
      range, 1-5). The mean and median overall survival times were 334 +/- 71 and 271
      days, respectively. There were no deaths within 30 days of treatment. Thirteen of
      the 20 patients had progression of disease. The mean and median progression-free
      survival times for these patients were 231 +/- 42 and 185 days, respectively.
      Patients with lesions that had a nodular angiographic appearance had longer
      progression-free survival than patients with lesions that had an infiltrative
      appearance (mean progression-free survival time, 249 vs 63 days). Patients with
      lesions that had a nodular angiographic appearance also survived significantly
      longer than those with lesions that had an infiltrative angiographic pattern
      (mean overall survival time, 621 vs 114 days; p = 0.0002). CONCLUSION: Hepatic
      arterial chemoembolization for liver-dominant metastasis of stage 4 melanoma is a
      safe treatment that results in longer survival than has occurred among historical
      controls. Patients with lesions that have a nodular tumor appearance on
      angiography survive significantly longer than patients with lesions that have an
      infiltrative appearance on angiography.

PMID- 18094300
TI  - CT-guided percutaneous chemical ablation of adrenal neoplasms.
AB  - OBJECTIVE: The objective of our study was to evaluate the feasibility and
      effectiveness of percutaneous chemical ablation of primary and metastatic adrenal
      neoplasms under CT guidance. MATERIALS AND METHODS: Thirty-seven patients with 46
      adrenal tumors underwent CT-guided percutaneous chemical ablation. The average
      (+/- SD) tumor diameter was 4.2 +/- 2.0 cm. Acetic acid was injected in lesions
      with a diameter of more than 3 cm, and ethanol was injected in lesions with a
      diameter of less than 3 cm. Eleven adrenal lesions were nonfunctional adenomas,
      six lesions were corticosteroid adenomas (bilateral lesions in one patient), nine
      lesions were aldosteronomas (bilateral lesions in two patients), and 20 were
      metastases (bilateral metastases in six patients). RESULTS: Tumor volume
      decreased gradually during the first 2 years after the procedure. For primary
      tumors, a complete response (CR) rate of 92.3% (24/26) and a partial response
      (PR) rate of 7.7% (2/26) were obtained, but for metastasis, a CR rate of 30%
      (6/20) and PR rate of 70% (14/20) were obtained 24 months after therapy. The
      level of corticosteroid in five patients (six tumors) with Cushing's syndrome was
      in the normal range 3 months after the procedure. Seven patients (nine tumors)
      with Conn's syndrome began receiving oral antihypertensive medications during the
      first month after the procedure to maintain normal blood pressure and the dose
      was gradually decreased after 1 month. No severe complications were encountered.
      CONCLUSION: CT-guided percutaneous chemical ablation of adrenal tumors is an
      effective, minimally invasive, and easily performed procedure.

PMID- 18094301
TI  - Side-hole catheter placement for hepatic arterial infusion chemotherapy in
      patients with liver metastases from colorectal cancer: long-term treatment and
      survival benefit.
AB  - OBJECTIVE: The objective of this study was to evaluate retrospectively
      correlations between catheter placement methods and treatment outcomes of
      patients treated with hepatic arterial infusion chemotherapy for unresectable
      liver metastases from colorectal cancer. MATERIALS AND METHODS: This study
      involved 135 patients with liver metastases from colorectal cancer who underwent
      intrahepatic chemotherapy using catheter-port systems. Complications, treatment
      discontinuation, hepatic progression, and survival of patients treated with each
      method were evaluated retrospectively using the Kaplan-Meier method. Conventional
      5-French end-hole catheter placement (n = 10) was compared with three side-hole
      catheter placement methods: 5-French side-hole catheter placement with a fixed
      catheter tip (original fixed catheter tip method, n = 77); long tapered side-hole
      catheter placement using a fixed catheter tip method (modified fixed catheter tip
      method, n = 24); and long tapered side-hole catheter inserted distally in the
      hepatic artery (long tapered catheter placement method, n = 24). RESULTS: The
      following treatment outcomes were significantly better for patients treated using
      the original or modified fixed catheter tip or long tapered catheter placement
      method than for those treated using the conventional method, respectively:
      hepatic arterial patency (1 year: 76.3%, 95.0%, and 94.4% vs 38.9%; p = 0.0014,
      0.0007, and 0.0006), catheter stability (1 year: 96.7%, 95.5%, and 95.2% vs
      42.9%; p < 0.0001, p = 0.0003, and p = 0.0009), time to treatment discontinuation
      (medians: 11.7, 14.4, and 12.4 vs 3.2 months; p < 0.0001, 0.0002, and 0.0019),
      time to hepatic progression (medians: 14.7, 15.7, and 15.8 vs 5.5 months; p =
      0.0049, 0.0141, and 0.0004), and overall survival (medians: 21.1, 22.5, and 23.1
      vs 13.1 months; p = 0.0146, 0.0036, and 0.0017). CONCLUSION: Compared with the
      conventional method, side-hole catheter placement methods allowed long-term
      intrahepatic chemotherapy and resulted in improved survival.

PMID- 18094302
TI  - Imaging in bariatric surgery: a guide to postsurgical anatomy and common
      complications.
AB  - OBJECTIVE: This article reviews the various bariatric surgical techniques and the
      associated imaging findings of normal postoperative anatomy and of common
      complications. CONCLUSION: Bariatric surgery is increasingly performed to control
      morbid obesity secondary to failed medical approaches. As a result, imaging plays
      an important role in postoperative evaluation and management. Practical knowledge
      of postsurgical anatomy allows accurate interpretation of imaging findings
      related to normal postsurgical anatomy and common postsurgical complications.

PMID- 18094303
TI  - Small and diminutive polyps detected at screening CT colonography: a decision
      analysis for referral to colonoscopy.
AB  - OBJECTIVE: The objective of this study was to assess the clinical and economic
      impact of colonoscopic referral for small and diminutive polyps detected at CT
      colonography (CTC) screening. MATERIALS AND METHODS: A decision analysis model
      was constructed incorporating the expected polyp distribution, advanced adenoma
      prevalence, colorectal cancer (CRC) risk, CTC performance, and costs related to
      CRC screening and treatment. The model conservatively assumed that CRC risk was
      independent of advanced adenoma size. The number of diminutive (< or = 5 mm),
      small (6-9 mm), and large (> or = 10 mm) CTC-detected polyps needed to be removed
      to detect one advanced adenoma or prevent one CRC over a 10-year time horizon was
      calculated. The cost-effectiveness of polypectomy was also assessed. RESULTS: The
      estimated 10-year CRC risk for unresected diminutive, small, and large polyps was
      0.08%, 0.7%, and 15.7%, respectively. The number of diminutive, small, and large
      polyps needed to be removed to avoid leaving behind one advanced adenoma was 562,
      71, and 2.5, respectively; similarly, 2,352, 297, and 10.7 polypectomies would be
      needed, respectively, to prevent one CRC over 10 years. The incremental cost
      effectiveness ratio of removing all diminutive and small CTC-detected polyps was
      $464,407 and $59,015 per life-year gained, respectively. Polypectomy for large
      CTC-detected polyps yielded a cost-saving of $151 per person screened.
      CONCLUSION: For diminutive polyps detected at CTC screening, the very low
      likelihood of advanced neoplasia and the high costs associated with polypectomy
      argue against colonoscopic referral, whereas removal of large CTC-detected polyps
      is highly effective. The yield of colonoscopic referral for small polyps is
      relatively low, suggesting that CTC surveillance may be a reasonable management
      option.

PMID- 18094304
TI  - CT colonography for incomplete or contraindicated optical colonoscopy in older
      patients.
AB  - OBJECTIVE: Our purpose was to assess the performance of CT colonography (CTC) in
      patients older than 60 years who were referred because colonoscopy was
      contraindicated or incomplete. MATERIALS AND METHODS: Over a 2-year period, 61
      patients underwent CTC at our institution, 42 of whom (26 women, 16 men) were 60
      years old or older (range, 60-87 years; mean age, 71 years). After 24-48 hours of
      ingesting only clear liquids and after colonic cleansing, fecal tagging, and
      automated CO2 insufflation, patients were scanned using a 16-MDCT scanner. Images
      were obtained with the patient in the supine and prone positions and as needed in
      the right or left decubitus position. Axial 2D and 3D endoluminal views were
      evaluated on a dedicated workstation. RESULTS: Contraindications to colonoscopy
      in 12 (29%) of the 42 patients were as follows: anticoagulation (n = 8),
      increased anesthesia risk (n = 3), and poor tolerance for colonoscopy preparation
      (n = 1). Incomplete colonoscopy in the other 30 patients (71%) was due to
      diverticular disease (n = 10), colonic redundancy (n = 10), adhesions (n = 3),
      residual colonic content (n = 3), sigmoid stricture (n = 1), ventral hernia (n =
      1), and unknown cause (n =2). No complications were observed. Optimal distention
      of the entire colon was achieved in 38 patients (90%). Thirty-nine (93%) of the
      42 patients had abnormal findings: diverticular disease (n = 25), one or more
      polyps (n = 22), a mass lesion (n = 1), a lipoma (n = 1), and inflammatory
      stricture (n = 1). Extracolonic findings potentially requiring further evaluation
      or treatment were observed in 26 patients (62%). CONCLUSION: CTC using CO2
      insufflation was well tolerated and successful in imaging the entire colon in
      most of the 42 patients, despite the presence of sigmoid diverticular disease or
      colonic redundancy.

PMID- 18094305
TI  - Conventional and reduced radiation dose of 16-MDCT for detection of
      nephrolithiasis and ureterolithiasis.
AB  - OBJECTIVE: Our purpose was to prospectively compare the reader compatibility and
      acceptability of a range of reduced-dose 16-MDCT images with standard-dose 16
      MDCT images for the detection of nephroureterolithiasis using a dose reduction
      simulation technique. SUBJECTS AND METHODS: The study was HIPAA compliant and
      institutional review board approved. Fifty consecutive patients with suspected
      nephrolithiasis were recruited to undergo conventional renal stone unenhanced 16
      MDCT with at least 160 mA. Noise was then artificially introduced to simulate
      levels of 70, 100, and 130 mA. Three blinded independent readers interpreted the
      original and simulated-dose scans for the location and number of renal and
      ureteral calculi and secondary signs of obstruction using a 5-point confidence
      scale. RESULTS: Reader acceptability of scans was inversely related to noise.
      There was no significant reduction in readers' confidence in detection or
      exclusion of renal collecting system calculi with simulated reduction of mA of
      70, 100, and 130 compared with the standard-dose study. However, for ureteral
      calcifications, there was a decrease in confidence for the detection or exclusion
      of ureterolithiasis at an mA of 70 (35 mAs). CONCLUSION: An mA as low as 70 (35
      mAs) is acceptable for evaluation of nephrolithiasis. However, the evaluation of
      ureterolithiasis is compromised with an mA of 70.

PMID- 18094306
TI  - Benign renal neoplasms in adults: cross-sectional imaging findings.
AB  - OBJECTIVE: A broad spectrum of benign renal neoplasms in adults shows
      characteristic ontogeny, histology, and tumor biology. Benign renal tumors are
      classified into renal cell tumors, metanephric tumors, mesenchymal tumors, and
      mixed epithelial and mesenchymal tumors. Select benign tumors show characteristic
      anatomic distribution and imaging features. However, because of overlapping of
      findings between benign and malignant renal tumors, histologic evaluation may be
      required to establish a definitive diagnosis. Accurate preoperative
      characterization facilitates optimal patient management. CONCLUSION: We attempt
      to provide a comprehensive, contemporary review of benign renal neoplasms that
      occur in adults, focusing on cross-sectional imaging characteristics.

PMID- 18094307
TI  - Pre- and postoperative evaluation of urethral diverticulum.
AB  - OBJECTIVE: The purpose of this article is to review the diagnostic imaging
      findings, differential diagnosis, complications, and postoperative imaging
      appearance of urethral diverticulum. CONCLUSION: With increased clinical
      awareness and advanced imaging techniques, diagnoses of urethral diverticula are
      more frequent, and radiologists need to be aware of the pre- and postoperative
      imaging appearances of this disorder.

PMID- 18094308
TI  - MR angiography of the renal arteries: intraindividual comparison of double-dose
      contrast enhancement at 1.5 T with standard dose at 3 T.
AB  - OBJECTIVE: The purpose of this study was to compare prospectively and within
      subjects use of 0.1 mmol/kg of gadodiamide at 3 T with use of 0.2 mmol/kg of
      gadodiamide at 1.5 T for MR angiography of the renal arteries. SUBJECTS AND
      METHODS: Twenty-two patients (14 men, eight women; mean age, 66.5 years)
      underwent two MR angiographic examinations of the renal arteries separated by at
      least 24 hours on whole-body 1.5- and 3-T MRI systems with a phase-encoded 3D
      spoiled breath-hold pulse sequence. Two radiologists blinded to the dose of
      contrast material assessed all image data in consensus for renal arterial disease
      and for image quality on a five-point Likert-type scale. Quantitative evaluation
      (vessel signal-to-noise ratio and vessel-muscle contrast-to-noise ratio) was
      performed by a third radiologist. RESULTS: Five renal arterial stenoses were
      detected with both techniques. The difference in mean image quality for the two
      doses and field strengths was not statistically significant. Overall vessel
      length and intraparenchymal branches, however, were better visualized with the
      double dose at 1.5 T. Signal-to-noise and contrast-to-noise ratios were
      significantly higher (both, p < 0.05) with the double dose at 1.5 T (125.7 and
      64.2, respectively) compared with the standard dose at 3 T (112.3 and 59.7).
      CONCLUSION: MR angiography can be performed with high diagnostic image quality at
      3 T with 0.1 mmol/kg of gadodiamide. Signal-to-noise and contrast-to-noise ratios
      are higher with a double dose at 1.5 T.

PMID- 18094309
TI  - Safety and efficacy of gadofosveset-enhanced MR angiography for evaluation of
      pedal arterial disease: multicenter comparative phase 3 study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of
      gadofosveset, a gadolinium-based albumin-binding MRI contrast agent, in patients
      with pedal arterial disease. SUBJECTS AND METHODS: A total of 185 adult patients
      with known or suspected pedal arterial disease were randomized in a group
      receiving 0.03 mmol/kg and a group receiving 0.05 mmol/kg of gadofosveset for MR
      angiography of the pedal arteries. Gadofosveset-enhanced and unenhanced time-of
      flight MR angiograms were compared with conventional angiograms, the standard of
      reference, for the presence of vascular stenosis. All patients underwent drug
      safety analysis. RESULTS: For each of three blinded readers, the specificity (21
      35%) of gadofosveset-enhanced MR angiography was a statistically significant (p <
      0.010) improvement over that of unenhanced MR angiography in the detection of
      clinically significant (> 50%) stenosis. The sensitivities of the two techniques
      were similar. For all blinded readers of MR angiograms, sensitivity, specificity,
      and accuracy were higher with use of the 0.03-mmol/kg dose of gadofosveset than
      with the 0.05-mmol/kg dose. In the 0.03-mmol/kg group, 28% of patients reported a
      total of 50 adverse events, 96% of which were reported as mild or moderate. In
      the 0.05-mmol/kg group, 28% of patients reported a total of 55 adverse events,
      98% of which were reported as mild or moderate. No patients died; one patient
      left the study because of myocardial infarction considered unrelated to the study
      drug. CONCLUSION: Because of markedly better efficacy than no contrast agent and
      a minimal and transient side-effect profile, 0.03 mmol/kg of gadofosveset was
      found safe and effective for MR angiography of patients with pedal arterial
      disease.

PMID- 18094310
TI  - Allergic-like breakthrough reactions to gadolinium contrast agents after
      corticosteroid and antihistamine premedication.
AB  - OBJECTIVE: The objective of our study was to determine the number and severity of
      allergic-like breakthrough reactions to i.v. gadolinium-containing contrast
      agents in children and adults after premedication with corticosteroids and
      antihistamines. MATERIALS AND METHODS: Contrast material reaction forms from the
      department of radiology for pediatric (under 19 years old) and adult patients
      were reviewed for the time period from January 1, 2001, through December 31,
      2006. All documented allergic-like reactions to i.v. gadolinium-containing
      contrast media after premedication with corticosteroids and antihistamines were
      identified. Forms were evaluated for reaction manifestations, management, and
      patient outcome. Our institutional electronic medical record system was accessed
      for each individual patient to identify pertinent medical history, including
      demographic information, history of allergic-like reaction to contrast media
      (gadolinium- or iodine-containing), and additional factors that led to
      prophylactic premedication. RESULTS: Eight patients experienced nine allergic
      like reactions after the i.v. administration of gadolinium-containing contrast
      media despite premedication. A single patient had two breakthrough reactions. Six
      breakthrough reactions were mild, and three were moderate. No severe or fatal
      breakthrough reaction occurred. Eight of nine breakthrough reactions occurred in
      adults. All patients who experienced breakthrough reactions had a history of
      allergic-like reaction to either gadolinium- or iodine-containing contrast media.
      CONCLUSION: Allergic-like reactions to gadolinium-containing contrast media can
      occur despite premedication with corticosteroids and antihistamines.

PMID- 18094311
TI  - High-intensity focused ultrasound: current potential and oncologic applications.
AB  - OBJECTIVE: The objective of this article is to introduce the reader to the
      principles and applications of high-intensity focused ultrasound (HIFU).
      CONCLUSION: Although a great deal about HIFU physics is understood, its clinical
      applications are currently limited, and multiple trials are underway worldwide to
      determine its efficacy.

PMID- 18094312
TI  - Sonographically guided 14-gauge core needle biopsy of breast masses: a review of
      2,420 cases with long-term follow-up.
AB  - OBJECTIVE: The objective of our study was to determine the diagnostic accuracy of
      sonographically guided core needle biopsy for breast masses by evaluating the
      outcomes of benign biopsies that had at least a 2-year follow-up. MATERIALS AND
      METHODS: In this retrospective study, we included a total of 2,420 lesions from
      2,198 women who had undergone sonographically guided 14-gauge core needle biopsy.
      For evaluating the diagnostic accuracy of this procedure, the pathologic results
      were reviewed and correlated with rebiopsy or long-term imaging follow-up.
      Agreement rate, high-risk underestimate rate, ductal carcinoma in situ (DCIS)
      underestimate rate, and false-negative rate were assessed. The false-negative
      diagnoses of core needle biopsy were reviewed in detail. RESULTS: The pathologic
      results for the core needle biopsies were malignant in 52%, high-risk in 4%, and
      benign in 44%. The agreement rate was 96% (2,328 of 2,420). The underestimate
      rate was 29% (36 of 126) for DCIS and 27% (25 of 93) for high-risk (52% for 27
      atypical ductal hyperplasia (ADH), 17% for 66 non-ADH). Of 1,071 benign lesions,
      malignancy was found at rebiopsy in 31 lesions (25 immediate and six delayed
      false-negative diagnoses), and the false-negative rate was 2.4% (31 of 1,312).
      The frequency of malignancy in lesions that had rebiopsy because of suspicious
      imaging findings (19.1%, 26 of 136) was significantly higher than that because of
      suspicious physical findings or request by patient or physician (0.9%, five of
      584). CONCLUSION: Sonographically guided 14-gauge core needle biopsy is an
      accurate method for evaluating breast masses. Imaging-pathologic correlation and
      follow-up of benign biopsy are essential for a successful breast biopsy program.

PMID- 18094313
TI  - Bilateral synchronous breast cancer in an Asian population: mammographic and
      sonographic characteristics, detection methods, and staging.
AB  - OBJECTIVE: This study was performed to compare the clinical and radiologic
      findings and pathologic staging between index cancer and contralateral
      synchronous breast cancers and to determine the roles of mammography and
      sonography in their detection. CONCLUSION: Additional contralateral breast
      cancers in bilateral synchronous breast cancers are apt to be small and less
      palpable and to have less suspicious imaging findings and less advanced cancer
      staging than the index cancer. Bilateral whole-breast sonography with mammography
      is useful in the early detection of contralateral synchronous breast cancer.

PMID- 18094314
TI  - Incidence and management of complex fibroadenomas.
AB  - OBJECTIVE: Complex fibroadenomas are a fibroadenoma subtype harboring one or more
      complex features. We sought to evaluate the incidence of complex fibroadenoma on
      biopsy and to propose decision criteria for managing patients with these breast
      lesions. MATERIALS AND METHODS: Complex fibroadenomas were diagnosed in 63 of 401
      fibroadenomas (15.7%) found at consecutive percutaneous needle or excisional
      surgical biopsy. We evaluated the clinical and imaging presentations of complex
      fibroadenomas; compared pathology at core and excisional biopsy; and contrasted
      age, pathology, and size of complex and simple fibroadenomas using the Student's
      t test. RESULTS: Patients with complex lesions were 18.5 years older (median age,
      47 years; range, 21-69 years) than patients with noncomplex fibroadenomas (median
      age, 28.5 years; range, 12-86 years) (p < 0.001). Complex fibroadenomas were half
      the size (average, 1.3 cm; range, 0.5-2.6 cm) of noncomplex fibroadenomas
      (average, 2.5 cm; range, 0.5-7.5 cm) (p < 0.001). Only one malignancy, an
      invasive lobular carcinoma, was found in 63 complex fibroadenomas (1.6%). This
      patient had atypical lobular hyperplasia at core needle biopsy. CONCLUSION:
      Approximately 16% of fibroadenomas are complex. Complex fibroadenomas are smaller
      and appear at an older age. At a mean follow-up of 2 years, we found a low
      incidence of malignancy in complex fibroadenomas. Women with complex
      fibroadenomas may therefore be managed with a conservative approach, similar to
      the approach now recommended for women with simple fibroadenomas.

PMID- 18094315
TI  - Effects of sublingual nitroglycerin on coronary lumen diameter and number of
      visualized septal branches on 64-MDCT angiography.
AB  - OBJECTIVE: This article describes the influence of sublingual nitroglycerin spray
      on the lumen diameter, number of side branches visualized, contrast-to-noise
      ratio (CNR), and signal-to-noise ratio (SNR) of the coronary arteries with MDCT
      angiography. SUBJECTS AND METHODS: Forty-two patients were prospectively included
      in this study: 21 were examined without sublingual nitroglycerin (group A), and
      21 were examined after the administration of sublingual nitroglycerin (group B).
      CT angiography was performed using a 64-MDCT scanner. Two blinded observers
      quantitatively assessed lumen diameter and volume in the left anterior descending
      artery (LAD) and the right coronary artery (RCA). The number of septal branches
      was counted. The SNR and CNR in the LAD and RCA were calculated in both groups.
      The number of clinical side effects was evaluated. RESULTS: The lumen diameters
      and the average volumes were significantly larger in group B than in group A. The
      number of septal branches visualized in group B was significantly higher than in
      group A. No statistically significant difference in SNR and CNR between the
      groups was shown. The number of side effects in the two groups was not
      significantly different. CONCLUSION: Sublingual nitroglycerin spray significantly
      dilates the coronary arteries and allows more septal branches to be visualized at
      coronary CT angiography without diminishing image quality or increasing the
      number of side effects.

PMID- 18094316
TI  - Cardiac hydatid disease: CT and MRI findings.
AB  - OBJECTIVE: The purpose of this article is to review the CT and MRI findings of
      cardiac hydatid disease. CONCLUSIONS: CT and MRI are helpful for localizing and
      defining the morphologic features of hydatid cysts. Specific signs include
      calcification of the cyst wall, presence of daughter cysts, and membrane
      detachment. CT best shows wall calcification, whereas MRI depicts the exact
      anatomic location and nature of the internal and external structures.

PMID- 18094317
TI  - Diagnostic accuracy of CT-guided core biopsy of ground-glass opacity pulmonary
      lesions.
AB  - OBJECTIVE: The purpose of our study was to evaluate the accuracy of CT-guided
      percutaneous core biopsy of ground-glass opacity (GGO) pulmonary lesions.
      MATERIALS AND METHODS: The study included 50 patients (24 men, 26 women; age
      range, 43-78 years) who had a GGO pulmonary lesion and underwent CT-guided core
      biopsy. Diagnostic accuracy was compared between two groups according to lesion
      size (< 2 cm vs > or = 2 cm) and GGO component (> 90% vs 50-90%). Each case was
      reviewed for complications, including pneumothorax, thoracostomy tube insertion,
      and hemoptysis. RESULTS: Malignancy was finally diagnosed in 33 patients,
      including three who underwent repeated biopsies, with 33 true-positive and three
      false-negative findings for an overall sensitivity of 92% (33/36). A benign
      lesion was finally diagnosed in 10 patients with one false-positive result, for a
      specificity of 90%. Two benign lesions without confirmative diagnosis because of
      loss of follow-up and five nondiagnostic samples were excluded from the
      calculations of sensitivity, specificity, and diagnostic accuracy. The overall
      diagnostic accuracy was 91%, with a positive predictive value of 97% and a
      negative predictive value of 75%. Sensitivity and accuracy were not significantly
      different between the two groups of lesion size and GGO components (p = 0.0491).
      Ten (18%) patients had pneumothorax, with one (2%) requiring placement of a
      thoracostomy tube. Mild hemoptysis occurred in seven (13%) patients. CONCLUSION:
      CT-guided core biopsy of GGO lesions can yield high diagnostic accuracy and
      acceptable complication rates approaching those of solid lesions.

PMID- 18094318
TI  - Increased echogenicity of renal cortex: a transient feature in acutely ill
      children.
AB  - OBJECTIVE: The purpose of our study was to determine the frequency of
      hyperechogenicity of renal parenchyma in children with acute abdominal illness
      and to evaluate the assumed transient feature of this hyperechogenicity.
      MATERIALS AND METHODS: Between January 2005 and February 2006, 189 consecutive
      patients (112 boys and 77 girls; mean age, 10 years) presenting with acute
      abdominal pain were examined with sonography. Patients with a known history of
      renal disease and those with acute urinary tract infection were excluded from the
      study. Echogenicity of the renal cortex in comparison with adjacent liver was
      recorded. Renal cortex echogenicity was divided into three groups; group 1, renal
      cortex echogenicity less than liver parenchyma echogenicity; group 2, renal
      cortex echogenicity similar to that of liver parenchyma; and group 3, renal
      cortex echogenicity greater than that of liver parenchyma. Patients with
      hyperechogenicity were reexamined with sonography after 2 weeks or more. The
      final sonographic diagnosis and clinical outcome were noted. RESULTS: Renal
      cortex echogenicity was equal to or greater than that of the liver parenchyma in
      18% (n = 34) of 189 patients. Increased echogenicity of the renal cortex returned
      to normal in 2 or more weeks in all patients. Three patients had no follow-up.
      Clinical diagnoses were idiopathic acute abdominal pain (n = 74), appendicitis (n
      = 83), mesenteric lymphadenitis (n = 15), ileocecitis (n = 7), gastroenteritis (n
      = 7), Crohn's disease (n = 1), intussusception (n = 1), and pneumonia (n = 1). No
      concurrent renal disease was diagnosed. CONCLUSION: Increased echogenicity of
      renal parenchyma in children with acute illness is a transient feature and does
      not necessarily indicate renal disease.

PMID- 18094319
TI  - Nonpalpable supraclavicular lymph nodes in lung cancer patients: preoperative
      characterization with 18F-FDG PET/CT.
AB  - OBJECTIVE: Our purpose was to evaluate the usefulness of integrated 18F-FDG
      PET/CT in the detection and characterization of nonpalpable supraclavicular lymph
      node metastasis in patients with the initial diagnosis of lung cancer. SUBJECTS
      AND METHODS: This study was conducted from May 2005 to May 2006 and included 32
      consecutively registered lung cancer patients in whom supraclavicular lymph nodes
      were not palpable but were identified on contrast-enhanced CT or exhibited
      increased FDG uptake on integrated PET/CT. Three patients had bilateral nodes,
      for a total of 35 nodes in the 32 patients. Results of cytologic analysis of a
      specimen obtained with sonographically guided fine-needle aspiration (n = 27),
      normal initial and follow-up sonographic findings (n = 3), and no change in the
      size of supraclavicular lymph nodes on follow-up sonography (n = 2) were the
      reference standards. The presence of supraclavicular lymph node metastasis was
      determined with integrated PET/CT (uptake greater than that of surrounding
      tissue) and contrast-enhanced CT (node short-axis diameter of 5 mm or more). The
      diagnostic efficacies of these methods in the detection of supraclavicular lymph
      node metastasis were compared. RESULTS: Supraclavicular lymph node metastasis was
      diagnosed cytologically in 12 (34%) of 35 lesions. The diagnostic accuracies of
      integrated PET/CT and contrast-enhanced CT in the detection of supraclavicular
      lymph node metastasis were 71% and 66%, respectively; the difference was not
      statistically significant. Although the difference was not statistically
      significant, the sensitivity (92%) and negative predictive value (93%) of
      integrated PET/CT were higher than those of contrast-enhanced CT. CONCLUSION:
      Because of its high sensitivity and negative predictive value, integrated PET/CT
      is useful in the detection and characterization of nonpalpable supraclavicular
      lymph nodes in lung cancer patients.

PMID- 18094320
TI  - Isoflurane is a potent modulator of extrasynaptic GABA(A) receptors in the
      thalamus.
AB  - Volatile anesthetics are used clinically to produce analgesia, amnesia,
      unconsciousness, blunted autonomic responsiveness, and immobility. Previous work
      has shown that the volatile anesthetic isoflurane, at concentrations that produce
      unconsciousness (250-500 microM), enhances fast synaptic inhibition in the brain
      mediated by GABA(A) receptors (GABA(A)-Rs). In addition, isoflurane causes
      sedation at concentrations lower than those required to produce unconsciousness
      or analgesia. In this study, we found that isoflurane, at low concentrations (25
      85 microM) associated with its sedative actions, elicits a sustained current
      associated with a conductance increase in thalamocortical neurons in the mouse
      ventrobasal (VB) nucleus. These isoflurane-evoked currents reversed polarity
      close to the Cl(-) equilibrium potential and were totally blocked by the GABA(A)
      R antagonist gabazine. Isoflurane (25-250 microM) produced no sustained current
      in VB neurons from GABA(A)-R alpha(4)-subunit knockout (Gabra4(-/-)) mice,
      although 250 microM isoflurane enhanced synaptic inhibition in VB neurons from
      both wild-type and Gabra4(-/-) mice. These data indicate an obligatory
      requirement for alpha(4)-subunit expression in the generation of the isoflurane
      activated current. In addition, isoflurane directly activated
      alpha(4)beta(2)delta GABA(A)-Rs expressed in human embryonic kidney 293 cells,
      and it was more potent at alpha(4)beta(2)delta than at alpha(1)beta(2)gamma(2)
      receptors (the presumptive extrasynaptic and synaptic GABA(A)-R subtypes in VB
      neurons). We conclude that the extrasynaptic GABA(A)-Rs of thalamocortical
      neurons are sensitive to low concentrations of isoflurane. In view of the crucial
      role of the thalamus in sensory processing, sleep, and cognition, the modulation
      of these extrasynaptic GABA(A)-Rs by isoflurane may contribute to the sedation
      and hypnosis associated with low doses of this anesthetic agent.

PMID- 18094321
TI  - Arginine 246 of the pretransmembrane domain 1 region alters 2,2,2
      trichloroethanol action in the 5-hydroxytryptamine3A receptor.
AB  - Ligand-gated ion channels participate in synaptic transmission, and they are
      involved in neurotransmitter release. The functions of the channels are regulated
      by a variety of modulators. The interaction of 2,2,2-trichloroethanol, the active
      hypnotic metabolite of chloral hydrate, with the 5-hydroxytryptamine (5-HT)
      (serotonin) type 3 receptor results in a positive allosteric modulation. We have
      demonstrated previously that arginine 246 (R246) located in the pretransmembrane
      domain 1 is critical for coupling agonist binding to gating. In this study, we
      examined the role of R246 in the action of trichloroethanol with a combination of
      mutagenesis and whole-cell patch-clamp techniques. The R246A mutation converted
      the partial agonist dopamine into a full agonist at the 5-HT(3A) receptor, and it
      facilitated activation of the mutant receptor by dopamine, suggesting an enhanced
      gating process due to the mutation. The positive modulation of the 5-HT(3A)
      receptor by trichloroethanol was dramatically reduced by the R246A mutation.
      Trichloroethanol had little agonist activity in the wild-type receptor (<1% of
      maximal 5-HT response). However, the R246A mutation significantly increased the
      direct activation of the receptor by trichloroethanol in the absence of agonist (
      approximately 10% of maximal 5-HT response). The current activated by
      trichloroethanol could be blocked by the competitive 5-HT(3) receptor antagonist
      tropanyl 3,5-dichlorobenzoate (MDL 72222), and it had a similar reversal
      potential to those of current activated by 5-HT. In addition, predesensitization
      of the mutant receptor by trichloroethanol prevented 5-HT from activating the
      receptor. These data suggest that R246 is a crucial site for mediating the
      actions of both agonists and modulators.

PMID- 18094322
TI  - Comments on "Ethanol sensitivity of GABAergic currents in cerebellar granule
      neurons is not increased by a single amino acid change (R100Q) in the alpha6
      GABA(A) receptor subunit".

PMID- 18094323
TI  - Comments on "Blockade of angiogenesis by small molecule antagonists to protease
      activated receptor-1: association with endothelial cell growth suppression and
      induction of apoptosis".

PMID- 18094324
TI  - ADHD in adults: a review of the literature.
AB  - OBJECTIVE: ADHD presents significant challenges to adults. The current review's
      goals are (a) to critically examine the current state of knowledge regarding ADHD
      in adults and (b) to provide clinicians with practice-friendly information
      regarding assessment, diagnosis, and treatment. METHOD: Searches of PsycINFO and
      Medline were conducted, and reference lists from articles and books were searched
      for additional relevant references. RESULTS/CONCLUSION: A valid and reliable
      assessment should be comprehensive and include the use of symptom rating scales,
      a clinical interview, neuropsychological testing, and the corroboration of
      patient reports. Specific diagnostic criteria that are more sensitive and
      specific to adult functioning are needed. In treatment, pharmacological
      interventions have the most empirical support, with the stimulants
      methylphenidate and amphetamine and the antidepressants desipramine and
      atomoxetine having the highest efficacy rates. Scientific research on
      psychosocial treatments is lacking, with preliminary evidence supporting the
      combination of cognitive behavioral therapy and medication.

PMID- 18094325
TI  - Anxiety, methylphenidate response, and working memory in children with ADHD.
AB  - OBJECTIVE: To investigate the effects of methylphenidate (MPH) on components of
      working memory (WM) in children with ADHD and determine whether MPH produces
      differential effects on WM in children with comorbid anxiety (ANX). METHOD:
      Participants were a clinical sample of 130 children with ADHD, aged 6 to 12 years
      old (32% comorbid ANX). Each child participated in an acute randomized, double
      blind, placebo-controlled, crossover trial with single challenges of three MPH
      doses. Four WM measures were used that varied in processing demands (storage
      versus manipulation of information) and modality (auditory-verbal; visual
      spatial). RESULTS: MPH improved auditory-verbal manipulation but only in the non
      ANX children with ADHD. It had no effect on auditory-verbal storage of
      information. Also, MPH improved the ability to manipulate visual-spatial
      information in both ADHD groups, but beneficial effects on visual-spatial storage
      were evident only in children without comorbid ANX. CONCLUSIONS: Findings provide
      insight into potential mechanisms underlying individual differences in treatment
      response in ADHD, which may facilitate more targeted treatments.

PMID- 18094326
TI  - High frequency of CD4+FoxP3+ cells in HTLV-1 infection: inverse correlation with
      HTLV-1-specific CTL response.
AB  - Evidence from population genetics, gene expression microarrays, and assays of ex
      vivo T-cell function indicates that the cytotoxic T lymphocyte (CTL) response to
      human T-lymphotropic virus type 1 (HTLV-1) controls the level of HTLV-1
      expression and the proviral load. The rate at which CTLs kill autologous HTLV-1
      infected lymphocytes differs significantly among infected people, but the reasons
      for such variation are unknown. Here, we demonstrate a strong negative cor
      relation between the frequency of CD4(+)FoxP3(+) Tax(-) regulatory T cells
      (T(regs)) in the circulation and the rate of CTL-mediated lysis of autologous
      HTLV-1-infected cells ex vivo. We propose that the frequency of CD4(+)FoxP3(+)
      Tax(-) T(regs) is one of the chief determinants of the efficiency of T cell
      mediated immune control of HTLV-1.

PMID- 18094327
TI  - Serglycin proteoglycan deletion induces defects in platelet aggregation and
      thrombus formation in mice.
AB  - Serglycin (SG), the hematopoietic cell secretory granule proteoglycan, is crucial
      for storage of specific secretory proteins in mast cells, neutrophils, and
      cytotoxic T lymphocytes. We addressed the role of SG in platelets using SG-/-
      mice. Wild-type (WT) but not SG-/- platelets contained chondroitin sulfate
      proteoglycans. Electron microscopy revealed normal alpha-granule structure in SG
      /- platelets. However, SG-/- platelets and megakaryocytes contained unusual
      scroll-like membranous inclusions, and SG-/- megakaryocytes showed extensive
      emperipolesis of neutrophils. SG-/- platelets had reduced ability to aggregate in
      response to low concentrations of collagen or PAR4 thrombin receptor agonist
      AYPGKF, and reduced fibrinogen binding after AYPGKF, but aggregated normally to
      ADP. 3H-serotonin and ATP secretion were greatly reduced in SG-/- platelets. The
      alpha-granule proteins platelet factor 4, beta-thromboglobulin, and platelet
      derived growth factor were profoundly reduced in SG-/- platelets. Exposure of P
      selectin and alphaIIb after thrombin treatment was similar in WT and SG-/-
      platelets. SG-/- mice exhibited reduced carotid artery thrombus formation after
      exposure to FeCl3. This study demonstrates that SG is crucial for platelet
      function and thrombus formation. We propose that SG-/- platelet function
      deficiencies are related to inadequate packaging and secretion of selected alpha
      granule proteins and reduced secretion of dense granule contents critical for
      platelet activation.

PMID- 18094328
TI  - The inhibitory receptor LILRB1 modulates the differentiation and regulatory
      potential of human dendritic cells.
AB  - Dendritic cells (DCs) link innate and adaptive immunity, initiating and
      regulating effector cell responses. They ubiquitously express members of the LILR
      (ILT, LIR, CD85) family of molecules, some of which recognize self-HLA molecules,
      but little is known of their possible functions in DC biology. We demonstrate
      that the inhibitory receptor LILRB1 (ILT2, LIR1, CD85j) is selectively up
      regulated during DC differentiation from monocyte precursors in culture.
      Continuous ligation of LILRB1 modulated cellular differentiation, conferred a
      unique phenotype upon the resultant cells, induced a profound resistance to CD95
      mediated cell death, and inhibited secretion of cytokines IL-10, IL-12p70, and
      TGF-beta. These features remained stable even after exposure of the cells to
      bacterial LPS. Ligated DCs exhibited poor stimulatory activity for primary and
      memory T-cell proliferative responses, but this was substantially reversed by
      blockade of CD80 or its preferred ligand CTLA-4, or by depleting CD4(+) CD25(+)
      CD127(lo) regulatory T cells. Our findings suggest that ligation of LILRB1 on DCs
      by self-HLA molecules may play a key role in controlling the balance between the
      induction and suppression of adaptive immune responses.

PMID- 18094329
TI  - The specificity of JAK3 kinase inhibitors.
AB  - PF-956980 is a selective inhibitor of JAK3, related in structure to CP-690550, a
      compound being evaluated in clinical trials for rheumatoid arthritis and
      prevention of allograft rejection. PF-956980 has been evaluated against a panel
      of 30 kinases, and found to have nanomolar potency against only JAK3. Cellular
      and whole blood activity of this compound parallels its potency and selectivity
      in enzyme assays. It was effective in vivo at inhibiting the delayed type
      hypersensivity reaction in mice. We compared 2 commercially available JAK3
      inhibitors (WHI-P131 and WHI-P154) in the same panel of biochemical and cellular
      assays and found them to be neither potent nor selective for JAK3. Both were
      found to be nanomolar inhibitors of the EGF receptor family of kinases. As these
      compounds have been used in numerous publications in the transplant and
      autoimmune disease literature, their specificity should be considered when
      interpreting these results.

PMID- 18094330
TI  - Leukotriene B4 activates T cells that inhibit B-cell proliferation in EBV
      infected cord blood-derived mononuclear cell cultures.
AB  - Epstein-Barr virus (EBV)-specific cellular memory is not transferred from mother
      to child. Therefore, EBV-induced B-cell proliferation in in vitro-infected cord
      blood mononuclear cell cultures is not inhibited. However, by addition of
      immunomodulators, polysaccharide K (PSK) or truncated thioredoxin (Trx80) that
      activate monocytes, EBV-specific T-cell response could be generated in such
      cultures. Presently, we demonstrate that leukotriene B(4) (LTB(4)) is involved in
      the effect of the immunomodulators. LTB(4) was detected in the medium, and T-cell
      activation was compromised by addition of leukotriene biosynthesis inhibitors.
      Moreover, we found that LTB(4) added to infected cultures, which did not receive
      the immunomodulators, induced functional activation of the T cells. LTB(4)
      activated the monocytes and acted directly on the T cells. In consequence,
      addition of LTB(4) inhibited the EBV-induced proliferation of B lymphocytes.
      Specific cytotoxicity could be generated by restimulation of the T cells. The
      experiments showed successive stages of T-cell activation in acquisition of their
      immunologic effector function. This is orchestrated by complex cellular
      interactions, and autocrine loops mediated by soluble factors-here interferon
      (IFN)-gamma, interleukin (IL)-15, IL-12, and LTB(4). Importantly, the results
      indicate that endogenous LTB(4) can induce T-cell activation that inhibits the
      EBV-induced proliferation of B lymphocytes.

PMID- 18094331
TI  - SWAP-70 deficiency causes high-affinity plasma cell generation despite impaired
      germinal center formation.
AB  - Germinal centers (GCs) are lymphoid tissue structures central to the generation
      of long-lived, high-affinity, antibody-forming B cells. However, induction,
      maintenance, and regulation of GCs are not sufficiently understood. The F-actin
      binding, Rac-interacting protein SWAP-70 is strongly expressed in activated B
      cells like those in B follicles. Recent work suggests that SWAP-70 is involved in
      B-cell activation, migration, and homing. Therefore, we investigated the role of
      SWAP-70 in the T-dependent immune response, in GC formation, and in
      differentiation into plasma and memory B cells. Compared with wt, sheep red blood
      cell (SRBC)-, or NP-KLH-immunized SWAP-70(-/-) mice have strongly reduced numbers
      of GCs and GC-specific B cells. However, SWAP-70(-/-) NP-specific B cells
      accumulate outside of the B follicles, and SWAP-70(-/-) mice show more plasma
      cells in the red pulp and in the bone marrow, and increased NP-specific Ig and
      antibody-forming B cells. Yet the memory response is impaired. Thus, SWAP-70
      deficiency uncouples GC formation from T-dependent antibody and long-lived plasma
      cell production and causes extrafollicular generation of high-affinity plasma
      cells, but does not adequately support the memory response.

PMID- 18094332
TI  - Sox18 and Sox7 play redundant roles in vascular development.
AB  - Mutations in SOX18 cause the human hypotrichosis-lymphedema-telangiectasia (HLT)
      syndrome. Their murine counterparts are the spontaneous ragged mutants, showing
      combined defects in hair follicle, blood vessel, and lymphatic vessel
      development. Mice null for Sox18 display only mild coat defects, suggesting a
      dominant-negative effect of Sox18/ragged mutations and functional redundancy
      between Sox18 and other Sox-F proteins. We addressed this point in zebrafish. The
      zebrafish homologs of Sox18 and of Sox7 are expressed in angioblasts and in the
      endothelial component of nascent blood vessels in embryos. Knockdown of either
      gene, using moderate doses of specific morpholinos, had minimal effects on
      vessels. In contrast, simultaneous knockdown of both genes resulted in multiple
      fusions between the major axial vessels. With combined use of transgenic lines
      and molecular markers, we could show that endothelial cells are specified, but
      fail to acquire a correct arteriovenous identity. Venous endothelial cell
      differentiation was more severely affected than arterial. Thus, sox7 and sox18
      play redundant but collectively essential roles in the establishment of proper
      arteriovenous identity in zebrafish. Our data suggest that a defect in
      arteriovenous identity could be responsible for the formation of telangiectases
      in patients with HLT.

PMID- 18094333
TI  - Increasing Wnt signaling in the bone marrow microenvironment inhibits the
      development of myeloma bone disease and reduces tumor burden in bone in vivo.
AB  - There is increasing evidence to suggest that the Wnt signaling pathway plays a
      critical role in the pathogenesis of myeloma bone disease. In the present study,
      we determined whether increasing Wnt signaling within the bone marrow
      microenvironment in myeloma counteracts development of osteolytic bone disease.
      C57BL/KaLwRij mice were inoculated intravenously with murine 5TGM1 myeloma cells,
      resulting in tumor growth in bone and development of myeloma bone disease.
      Lithium chloride (LiCl) treatment activated Wnt signaling in osteoblasts,
      inhibited myeloma bone disease, and decreased tumor burden in bone, but increased
      tumor growth when 5TGM1 cells were inoculated subcutaneously. Abrogation of beta
      catenin activity and disruption of Wnt signaling in 5TGM1 cells by stable
      overexpression of a dominant-negative TCF4 prevented the LiCl-induced increase in
      subcutaneous growth but had no effect on LiCl-induced reduction in tumor burden
      within bone or on osteolysis in myeloma-bearing mice. Together, these data
      highlight the importance of the local microenvironment in the effect of Wnt
      signaling on the development of myeloma bone disease and demonstrate that,
      despite a direct effect to increase tumor growth at extraosseous sites,
      increasing Wnt signaling in the bone marrow microenvironment can prevent the
      development of myeloma bone disease and inhibit myeloma growth within bone in
      vivo.

PMID- 18094334
TI  - Neuromyelitis optica-IgG in childhood inflammatory demyelinating CNS disorders.
AB  - OBJECTIVE: To determine seroprevalence of neuromyelitis optica (NMO)-IgG in
      childhood CNS inflammatory demyelinating disorders. METHODS: We analyzed
      demographic, clinical, and radiologic data in a blinded fashion and assessed
      serum NMO-IgG status for 87 children: 41 with relapsing-remitting multiple
      sclerosis (RRMS), 17 with NMO, 13 with monophasic/recurrent optic neuritis (ON),
      13 with transverse myelitis, of whom 10 were longitudinally extensive on MRI
      spine (LETM), and another 3 with LETM in the context of acute disseminated
      encephalomyelitis (ADEM). RESULTS: Ten of the 87 children (11%) were
      seropositive. Eight of 17 with NMO (47%) were seropositive (7 of 9 with relapsing
      NMO [78%], 1 of 8 with monophasic NMO [12.5%]). Two other children were
      seropositive: 1 of 5 with recurrent ON and one child with recurrent LETM. No
      seropositive case was identified among 41 with RRMS (14% of whom had LETM at some
      point in their clinical course), 8 with monophasic ON, 9 with monophasic LETM, or
      3 with LETM in the context of ADEM. CONCLUSIONS: The similar frequency of
      neuromyelitis optica (NMO)-IgG in both childhood and adult cases of NMO, and its
      rarity in relapsing-remitting multiple sclerosis, supports the concept that these
      diseases have a similar pathogenesis in childhood and adulthood. It is noteworthy
      that none of nine children with monophasic longitudinally extensive transverse
      myelitis (LETM) was NMO-IgG-seropositive. Furthermore, LETM does not appear to be
      as predictive of an NMO spectrum disorder in children as it is in adults.
      Longitudinal studies of larger pediatric LETM cohorts are required to ascertain
      whether the absence of NMO-IgG is a negative predictor for relapse in this
      childhood entity.

PMID- 18094335
TI  - Physical activity and dementia risk in the elderly: findings from a prospective
      Italian study.
AB  - OBJECTIVE: To examine the effect of physical activity on risk of developing
      Alzheimer disease (AD) and vascular dementia (VaD) in the elderly. METHODS: Data
      are from a prospective population-based cohort of 749 Italian subjects aged 65
      and older who, in 1999/2000, were cognitively normal at an extensive assessment
      for clinically overt and preclinical dementia and, in 2003/2004, underwent follow
      up for incident dementia. Baseline physical activity was measured as energy
      expenditure on activities of different intensity (walking, stair climbing,
      moderate activities, vigorous activities, and total physical activity). RESULTS:
      Over 3.9 +/- 0.7 years of follow-up there were 86 incident dementia cases (54 AD,
      27 VaD). After adjustment for sociodemographic and genetic confounders, VaD risk
      was significantly lower for the upper tertiles of walking (hazard ratio [HR]
      0.27, 95% CI 0.12 to 0.63), moderate (HR 0.29, 95% CI 0.12 to 0.66), and total
      physical activity (HR 0.24, 95% 0.11 to 0.56) compared to the corresponding
      lowest tertile. The association persisted after accounting for vascular risk
      factors and overall health status. After adjustment for sociodemographic and
      genetic confounders, AD risk was not associated with measures of physical
      activity and results did not change after further adjustment for vascular risk
      factors and overall health and functional status. CONCLUSIONS: In this cohort,
      physical activity is associated with a lower risk of vascular dementia but not of
      Alzheimer disease. Further research is needed about the biologic mechanisms
      operating between physical activity and cognition.

PMID- 18094336
TI  - GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease.
AB  - BACKGROUND: Pelizaeus-Merzbacher-like disease (PMLD) is a genetically
      heterogeneous disorder within the group of hypomyelinating leukoencephalopathies.
      Mutations of the gap junction protein alpha 12 (GJA12) gene are known to cause
      one autosomal recessive PMLD form. Few patients with GJA12 mutated PMLD have been
      reported, and to date, the frequency as well as the genotypic and phenotypic
      spectrum of GJA12 related PMLD is unclear. METHODS: We report mutation analysis
      of the GJA12 gene in a clinical and radiologic well-characterized multiethnic
      cohort of 193 patients with PMLD from 182 families. RESULTS AND CONCLUSIONS: Only
      16 patients (8.3%) from 14 families (7.7%) carry GJA12 mutations including five
      families where we detected only one mutated allele. Among those, we identified 11
      novel alterations. Thus, GJA12 mutations are a rather rare cause for Pelizaeus
      Merzbacher-like disease. The clinical phenotype of patients with a GJA12 mutation
      was evaluated and is overall comparable to the clinical features seen in mild
      forms of proteolipid protein 1 (PLP1) related disorder but with better cognition
      and earlier signs of axonal degeneration.

PMID- 18094337
TI  - Comment: Limited efficacy of gastrointestinal decontamination in severe slow
      release carbamazepine overdose.

PMID- 18094339
TI  - Francke's legacy--40 years of clinical pharmacy.

PMID- 18094340
TI  - Use of renin-angiotensin-aldosterone system inhibitors within the first eight to
      twelve weeks after renal transplantation.
AB  - OBJECTIVE: To evaluate the safety and efficacy of early initiation of inhibitors
      of the renin-angiotensin-aldosterone system (RAAS) in renal transplant patients.
      DATA SOURCES: A literature search was conducted using MEDLINE (1950-September
      2007), PubMed (1966-September 2007), and International Pharmaceutical Abstracts
      (1970-September 2007) with combinations of the following terms: angiotensin
      converting enzyme (ACE) inhibitors, angiotensin II type 1 receptor blockers
      (ARBs), and kidney transplant. Articles obtained from this search were cross
      referenced and bibliographies were checked for all relevant information. STUDY
      SELECTION AND DATA EXTRACTION: All articles that examined the early (within 12
      wk) initiation of either an ACE inhibitor or an ARB in renal transplant patients
      were included. DATA SYNTHESIS: A search of the literature revealed 7 studies that
      had examined the safety or efficacy of early use of ACE inhibitors and ARBs in
      posttransplant patients. One study examined only plasma levels of a common marker
      for tissue fibrosis and one included only patients who had early graft
      dysfunction. Of the other 5 studies, 3 primarily reported safety endpoints and 2
      reported clinical efficacy endpoints. Safety data in patients with functioning
      grafts (serum creatinine ranged from <2.5 to 3.0 mg/dL) show that early therapy
      with inhibitors of the RAAS did not result in appreciable increases in serum
      creatinine or potassium levels after up to 9 months of therapy. Results from the
      efficacy trials indicate that early initiation of an ACE inhibitor may be more
      effective than a beta-blocker in reducing left ventricular hypertrophy and
      proteinuria after 24 months of treatment. CONCLUSIONS: It appears that the early
      initiation of RAAS inhibitors is safe in posttransplant patients with functioning
      grafts. It is reasonable to consider these agents as first-line pharmacotherapy
      in patients with hypertension and compelling indications (ie, diabetes or heart
      failure) in the first 12 weeks following transplant. Data are insufficient to
      recommend these drugs in patients with early graft dysfunction.

PMID- 18094341
TI  - Faropenem medoxomil.
AB  - OBJECTIVE: To review the literature concerning the in vitro activity,
      pharmacokinetic properties, in vivo efficacy, and adverse events associated with
      a new penem antibiotic, faropenem medoxomil. DATA SOURCES: We conducted a search
      of MEDLINE/PubMed and International Pharmaceutical Abstracts databases for
      articles or abstracts using the terms faropenem, faropenem daloxate, faropenem
      medoxomil, SUN5555, SY5555, WY49605, RU67655, ALP201, BLA 857, and YM 044 and
      published through July 2007. Information on poster presentations was obtained
      from the drug's manufacturer. Additional articles were identified from citations
      in the bibliographies of review articles. Articles written in languages other
      than English were excluded. STUDY SELECTION AND DATA EXTRACTION: All published
      reports that evaluated faropenem (or its chemical synonyms) and faropenem
      medoxomil were used in this review. Abstracts subsequently published as full
      reports were excluded, and only the resulting reports were included. Abstracts
      without subsequently published reports were included. DATA SYNTHESIS: The in
      vitro activity of faropenem has been evaluated extensively against respiratory
      pathogens and less extensively against aerobic gram-positive, gram-negative, and
      anaerobic organisms. Prospective, randomized, multicenter clinical trials have
      demonstrated noninferiority of faropenem to comparators for the treatment of
      acute bacterial sinusitis, community-acquired pneumonia, acute exacerbation of
      chronic bronchitis, and uncomplicated skin and skin structure infections. Adverse
      events associated with faropenem appear to be minimal and include nausea,
      vomiting, and diarrhea. CONCLUSIONS: Faropenem has demonstrated excellent in
      vitro activity against common respiratory pathogens, many aerobic gram-positive
      organisms, and anaerobes. Activity against gram-negative organisms is more
      reserved. In vivo data suggest that faropenem is efficacious in treating
      community-acquired infections including uncomplicated skin and skin structure
      infections; however, more data may help to characterize faropenem's place in
      antimicrobial therapy. Replidyne, Inc., the manufacturer of faropenem, is
      conducting studies to address the Food and Drug Administration's concerns that
      resulted in a nonapprovable letter in October 2006.

PMID- 18094342
TI  - Characteristics and reasons associated with nonacceptance of selective serotonin
      reuptake inhibitor treatment.
AB  - BACKGROUND: Studies have shown that up to 38% of patients who start treatment
      with antidepressants fill only a single prescription at the pharmacy, apparently
      not accepting treatment. OBJECTIVE: To determine characteristics and reasons
      associated with nonacceptance of selective serotonin-reuptake inhibitor (SSRI)
      treatment. METHODS: A retrospective study was conducted in 37 community
      pharmacies in the Netherlands; patients who presented a prescription from a
      general practitioner (GP) for a newly started SSRI treatment were selected.
      Nonaccepters were defined as patients who filled only one SSRI prescription;
      patients who received at least 3 fills of an SSRI prescription were defined as
      accepters. Patient characteristics were obtained from automated dispensing
      records and from questionnaires. Areas of evaluation included sociodemographics,
      disease, and treatment. Nonaccepters were asked their reasons for not filling
      second prescriptions. RESULTS: Of the patients who started SSRI treatment, 22.0%
      were nonaccepters, filling only a single prescription. Fifty-seven nonaccepters
      and 128 accepters were included in our analysis. Nonacceptance was more common
      among patients with a low level of education (OR 2.6; 95% CI 1.1 to 5.9) and in
      patients who reported nonspecific symptoms like fatigue, stress, and restlessness
      as the reason for SSRI use (OR 2.7; 95% CI 1.4 to 5.5). Of the nonaccepters,
      29.8% (n = 17) did not start SSRI use, and 70.2% (n = 40) discontinued SSRI use
      within 2 weeks. Fear of adverse effects and the actual occurrence of adverse
      effects were main reasons for not accepting SSRI treatment. Of the nonaccepters,
      55.0% discontinued treatment without informing their GPs. CONCLUSIONS: Acceptance
      of SSRI treatment is a decisive moment in a patient's adherence to treatment
      initiated by his or her GP and deserves more attention; GPs and pharmacists
      should address treatment issues, especially in groups at risk for nonacceptance.

PMID- 18094343
TI  - Sipuleucel-T: a vaccine for metastatic, asymptomatic, androgen-independent
      prostate cancer.
AB  - OBJECTIVE: To review the design, efficacy, safety, dosing, therapeutic, and
      pharmacoeconomic considerations of sipuleucel-T, an investigational, autologous,
      dendritic, cell-based prostate cancer vaccine. DATA SOURCES: English-language
      literature searches of MEDLINE (1966-September 2007) and the Cochrane Database
      (2007, Issue 3) were performed using the terms sipuleucel-T, APC8015, and
      prostate cancer vaccine. Other data sources were identified from bibliographies
      of selected articles and from press releases. STUDY SELECTION AND DATA
      EXTRACTION: All published articles or abstracts on human studies of sipuleucel-T
      for androgen-independent prostate cancer (AIPC) were reviewed for inclusion.
      Manufacturer Web sites, Food and Drug Administration (FDA) documents, and the
      clinical trials registry were used to obtain information regarding ongoing
      clinical trials. DATA SYNTHESIS: AIPC is an incurable disease with a median
      survival rate of 18-20 months. Docetaxel-based chemotherapy is currently the only
      FDA-approved treatment for AIPC with a survival benefit (2.4 mo). Sipuleucel-T is
      a novel active cellular immunotherapy under investigation for the treatment of
      metastatic, asymptomatic AIPC. In clinical trials, the primary endpoint of time
      to disease progression was not met; however, an underpowered analysis of data
      suggests that sipuleucel-T prolongs survival by a median of 4.5 months compared
      with placebo. Sipuleucel-T has been relatively well tolerated, although a
      possible increased risk of cerebrovascular events may exist. In May 2007, the FDA
      did not approve the biologics license application for sipuleucel-T since the
      primary endpoint of the Phase 3 trials was not met. However, its approval will be
      reconsidered by the FDA once interim survival results from an ongoing Phase 3
      trial, IMPACT, are determined. These data are anticipated to be released in the
      fourth quarter of 2008. CONCLUSIONS: Metastatic AIPC is an incurable disease that
      currently has limited treatment options. Approval of sipuleucel-T hinges on
      results from the IMPACT trial. If improved survival is shown, sipuleucel-T may
      become the first approved active cellular immunotherapy for treating metastatic,
      asymptomatic AIPC.

PMID- 18094344
TI  - Phosphodiesterase-5 inhibitors for lower urinary tract symptoms in men.
AB  - OBJECTIVE: To review the efficacy of phosphodiesterase-5 (PDE-5) inhibitors for
      the treatment of lower urinary tract symptoms in men. DATA SOURCES: MEDLINE and
      International Pharmaceutical Abstracts were searched (1970-August 2007) using the
      terms phosphodiesterase inhibitor, sildenafil, vardenafil, tadalafil, lower
      urinary tract symptoms, and benign prostatic hypertrophy. STUDY SELECTION AND
      DATA EXTRACTION: English-language clinical trials, case reports, and background
      material were evaluated for safety and efficacy data. References of reviewed
      articles were examined and used to identify additional sources. DATA SYNTHESIS:
      Erectile dysfunction (ED) and lower urinary tract symptoms have numerous shared
      risk factors and are common in aging men. PDE-5 inhibitors may relax urinary
      tract smooth muscle tissue, which has led to interest in their utility for lower
      urinary tract symptoms. Six 12 week clinical trials were identified. Three
      uncontrolled trials (N = 168) examined the effects of on-demand sildenafil ED
      dosing on lower urinary tract symptoms. The 2 largest trials found that, the
      greater the ED response, the larger the reduction in lower urinary tract
      symptoms. A single prospective placebo-controlled trial (N = 369) studied
      sildenafil 100 mg daily in men with ED and lower urinary tract symptoms. Lower
      urinary tract symptoms improved significantly in the sildenafil group; patients
      with the worst lower urinary tract symptoms experienced the greatest benefits. An
      open-label trial (N = 62) compared daily sildenafil 25 mg, alfuzosin 10 mg, or
      sildenafil 25 mg plus alfuzosin 10 mg on ED and lower urinary tract symptoms.
      Combination therapy resulted in greater improvements in ED and lower urinary
      tract symptoms and urinary flow than did either drug alone. The effects of daily
      tadalafil 20 mg were studied in 281 men with lower urinary tract symptoms
      independent of ED. Tadalafil produced statistically significant but clinically
      modest improvements in lower urinary tract symptoms when compared with placebo.
      CONCLUSIONS: PDE-5 inhibitors consistently produced modest reductions in lower
      urinary tract symptoms. Further studies are needed to fully elucidate the
      efficacy, cost effectiveness, safety, and appropriate place in therapy of PDE-5
      inhibitors. At this time, data are insufficient to routinely recommend chronic
      use of PDE-5 inhibitors for lower urinary tract symptoms in men.

PMID- 18094345
TI  - Monitoring of anthracycline-induced cardiotoxicity.
AB  - OBJECTIVE: To review the literature regarding the appropriate monitoring for
      anthracycline-induced cardiotoxicity. DATA SOURCES: A MEDLINE search of the
      literature was performed (1966-August 2007). Search terms included anthracycline,
      cardiotoxicity, and monitoring. Additional references were identified through
      bibliographic reviews. DATA SYNTHESIS: Anthracycline medications are effective in
      the treatment of many malignancies but their use is limited by their associated
      cardiotoxicity. The focus of anthracycline-induced cardiotoxicity prevention has
      been on monitoring cardiac function during treatment; however, a consensus on the
      most appropriate way to monitor patients is not available. Most guidelines lack
      specific details on the appropriate methods of cardiac evaluation and schedule.
      One guideline that does provide specific recommendations on both the method of
      evaluation and schedule has been criticized for being too restrictive, costly,
      and lacking in evidentiary support. The literature is insufficient in evaluation
      of the predictive value of cardiac function monitoring by echocardiography or
      radionuclide angiography during anthracycline therapy and the future development
      of cardiotoxicity, the necessity of baseline cardiac function monitoring, the
      optimal follow-up cardiac evaluation schedule, and the addition of risk
      stratification to monitoring schemes. CONCLUSIONS: Although guidelines are
      inadequate to predict and prevent anthracycline-induced cardiotoxicity, until
      further research is available, following one of the existing guidelines to
      monitor for this adverse effect is a practical solution.

PMID- 18094346
TI  - Timing of blood pressure measurement related to caffeine consumption.
AB  - OBJECTIVE: To determine whether patients should wait 30 minutes after caffeine
      consumption to have their blood pressure measured. DATA SOURCES: Literature was
      obtained by searching MEDLINE (1980-September 2007), International Pharmaceutical
      Abstracts (1980-September 2007), and the Cochrane Database of Systematic Reviews
      (1994-September 2007). Search terms included caffeine and blood pressure.
      Literature was also obtained from citations in relevant articles. STUDY SELECTION
      AND DATA EXTRACTION: Articles that examined caffeine's acute effect on blood
      pressure were reviewed, with additional focus on caffeine tolerance and
      hypertensive status. DATA SYNTHESIS: Caffeine appears to affect blood pressure
      through adenosine receptor inhibition and an increased release of select
      neurotransmitters. Caffeine levels peak 30-120 minutes after oral intake and
      caffeine's half-life is 3-6 hours. The effect of caffeine on blood pressure has
      been examined for decades, with variable results depending on factors such as
      population examined (eg, hypertensive status, physical stressors, age) and study
      design (eg, acute effects, chronic ingestion, retrospective epidemiologic
      review). Caffeine tolerance diminishes the acute effect of caffeine on blood
      pressure, and hypertensive individuals are more susceptible to blood pressure
      changes. Reviews of caffeine's acute effect on blood pressure indicate changes of
      3-15 mm Hg systolic and 4-13 mm Hg diastolic. Typically, blood pressure changes
      occur within 30 minutes, peak in 1-2 hours, and may persist for more than 4
      hours. CONCLUSIONS: Having a patient abstain from caffeine for 30 minutes prior
      to blood pressure monitoring is not adequate to avoid caffeine's potential
      effects. An alternative approach to blood pressure monitoring would be to ask the
      patient about recent caffeine consumption and interpret the blood pressure
      reading based on this information. In addition, healthcare practitioners should
      provide education regarding caffeine's effects.

PMID- 18094347
TI  - Methotrexate-induced papular eruption following treatment of psoriasis.
AB  - OBJECTIVE: To report a case of a diffuse papular eruption following treatment of
      psoriasis with methotrexate injections. CASE REPORT: A 52-year-old woman
      presented with an extensive flare of psoriasis associated with joint pain,
      especially in her knees and elbows. She was treated with intramuscular injections
      of methotrexate 20 mg/wk. Ten hours after the second methotrexate injection, the
      patient experienced a diffuse pruritic papular eruption located mainly on the
      limbs. Histology showed foci of dyskeratosis in the mucosal layer and a
      polymorphic perivascular inflammatory infiltrate of the papillary dermis,
      suggesting a drug-induced skin reaction. According to the Naranjo probability
      scale, the papular eruption was probably caused by methotrexate. The drug was
      discontinued and papular lesions gradually disappeared. DISCUSSION: Methotrexate
      induced papular eruption is rarely reported shortly after beginning methotrexate
      therapy in patients with acute exacerbation of collagen vascular diseases.
      Methotrexate-induced papular eruption following treatment of psoriasis has not
      been previously reported. CONCLUSIONS: The pathogenesis of methotrexate-induced
      papular eruption in collagen vascular diseases may suggest cutaneous small-vessel
      vasculitis. In our patient, histology showed aspects of drug-induced skin
      reaction without vasculitis. Pathogenesis of methotrexate-induced papular
      eruption in psoriasis may involve immune mechanisms other than those of
      methotrexate-induced cutaneous vasculitis in collagen vascular disease.

PMID- 18094348
TI  - Quality of anticoagulation monitoring in nonvalvular atrial fibrillation
      patients: comparison of anticoagulation clinic versus usual care.
AB  - BACKGROUND: Prior research suggests that receiving specialized anticoagulation
      services enables patients to achieve better clinical outcomes. OBJECTIVE: To
      assess the quality of anticoagulation therapy in patients with atrial
      fibrillation who were enrolled in an anticoagulation clinic (ACC) versus usual
      care (UC). METHODS: Using Sharp Rees-Stealy physician group claims data, we
      estimated time spent in therapeutic range and time to first major bleeding
      episode or stroke for ACC and UC patients. t-Tests were used to compare time in
      therapeutic range proportions, and Kaplan-Meier survival analysis was performed
      to compare rates of bleeding and stroke between groups. RESULTS: We identified
      1107 patients (351 ACC, 756 UC) treated with anticoagulation therapy for atrial
      fibrillation with more than one international normalized ratio (INR) reported
      between March 2001 and March 2004. ACC patients spent a greater proportion
      (68.14%) of time in therapeutic range compared with UC patients (42.07%; p <
      0.001). There was a significant difference between groups in average time between
      INR tests (ACC = 14.31 days, UC = 18.39 days; p < 0.001). ACC patients were 59%
      less likely to experience a bleed following the index date than were UC patients
      (HR = 0.41; 95% CI 0.2444 to 0.6999; p = 0.001), but type of care was not a
      significant predictor for stroke (HR = 0.95; 95% CI 0.5125 to 1.7777; p value
      NS). CONCLUSIONS: Results from this observational study reinforce the positive
      impact that anticoagulation services have on anticoagulation therapy outcomes,
      emphasizing the importance of providing such services for patients undergoing
      treatment with warfarin.

PMID- 18094349
TI  - Accuracy of medication histories: the first step of medication reconciliation.

PMID- 18094350
TI  - Differences between ceftriaxone and cefotaxime: microbiological inconsistencies.
AB  - OBJECTIVE: To review data to determine why pneumococcal isolates appear to be
      increasingly resistant to cefotaxime, historically regarded as having the same in
      vitro susceptibility to ceftriaxone, and what this observation might imply
      clinically. DATA SOURCES: Literature was accessed through MEDLINE (1966-October
      2007) using the MeSH terms cefotaxime, ceftriaxone, susceptibility, microbial
      sensitivity tests, antibiotics, pneumococcal infections, Streptococcus
      pneumoniae, resistance, and cephalosporin resistance. Abstracts and surveillance
      databases were reviewed and unpublished data were provided by state departments
      of health and institutions. STUDY SELECTION AND DATA EXTRACTION: All articles
      published in the English language that were identified from the data sources were
      evaluated. DATA SYNTHESIS: An experimental model of pneumococcal infection in
      mice conducted 2 decades ago predicted that the delta T minimum inhibitory
      concentration (MIC) varied less for ceftriaxone than for cefotaxime. Studies of
      plasma and serum concentrations show that ceftriaxone remains at a concentration
      above the S. pneumoniae MIC for 100% of the dosing interval at 12 hours. Types of
      MIC susceptibility test methods for ceftriaxone and cefotaxime used against S.
      pneumoniae respiratory isolates were found to be similar. Data from state and
      county health departments found microbiological discrepancies between ceftriaxone
      and cefotaxime. In areas with high rates of penicillin-resistant S. pneumoniae
      (PRSP), isolates were twice as susceptible to ceftriaxone versus cefotaxime.
      Surveillance databases consistently show differences between susceptibility of S.
      pneumoniae to cefotaxime versus ceftriaxone over time. MIC and pulsed-field gel
      electrophoresis studies suggest that phenotypic discrepancies may account for
      penicillin resistance. Ongoing studies are examining S. pneumoniae isolates at
      the molecular level to determine the basis of difference in resistance to
      cefotaxime and ceftriaxone. CONCLUSIONS: An increase in rates of PRSP and
      differences in S. pneumoniae isolate susceptibility between ceftriaxone and
      cefotaxime emphasize the necessity for hospital laboratories to detect these
      changes as they occur. Clinicians should select the most appropriate agent for
      patients with S. pneumoniae.

PMID- 18094351
TI  - A mutation in the inner mitochondrial membrane peptidase 2-like gene (Immp2l)
      affects mitochondrial function and impairs fertility in mice.
AB  - The mitochondrion is involved in energy generation, apoptosis regulation, and
      calcium homeostasis. Mutations in genes involved in mitochondrial processes often
      result in a severe phenotype or embryonic lethality, making the study of
      mitochondrial involvement in aging, neurodegeneration, or reproduction
      challenging. Using a transgenic insertional mutagenesis strategy, we generated a
      mouse mutant, Immp2lTg(Tyr)979Ove, with a mutation in the inner mitochondrial
      membrane peptidase 2-like (Immp2l) gene. The mutation affected the signal peptide
      sequence processing of mitochondrial proteins cytochrome c1 and glycerol
      phosphate dehydrogenase 2. The inefficient processing of mitochondrial membrane
      proteins perturbed mitochondrial function so that mitochondria from mutant mice
      manifested hyperpolarization, higher than normal superoxide ion generation, and
      higher levels of ATP. Homozygous Immp2lTg(Tyr)979Ove females were infertile due
      to defects in folliculogenesis and ovulation, whereas mutant males were severely
      subfertile due to erectile dysfunction. The data suggest that the high superoxide
      ion levels lead to a decrease in the bioavailability of nitric oxide and an
      increase in reactive oxygen species stress, which underlies these reproductive
      defects. The results provide a novel link between mitochondrial dysfunction and
      infertility and suggest that superoxide ion targeting agents may prove useful for
      treating infertility in a subpopulation of infertile patients.

PMID- 18094352
TI  - Expression and regulation of functional oxytocin receptors in bovine T
      lymphocytes.
AB  - The corpus luteum (CL) produces oxytocin (OXT), which has been proposed to
      regulate the pulsatile release of prostaglandin F2alpha during luteolysis in
      ruminants. This action of OXT is mediated via oxytocin receptors (OXTRs) present
      on uterine epithelial cells. It is hypothesized that luteal OXT acts as a
      paracrine regulator of resident immune cells. In the present study, OXTR mRNA
      expression in bovine lymphocytes was analyzed, as well as its regulation during
      the estrous cycle. OXTR transcripts were observed in freshly purified bovine
      peripheral blood mononuclear cells and T lymphocytes. OXTR mRNA in bovine
      lymphocytes on Day 3 was numerically greater than but not significantly different
      from that of Day 19 of the estrous cycle (P=0.091). In cultured T cells,
      estradiol (E2) treatment significantly increased the steady-state concentrations
      of OXTR mRNA, but the stimulatory effect of E2 was inhibited by the addition of
      progesterone (P4). Each of the major T cell subsets (CD4+, CD8+, and gamma
      delta+) expressed OXTR mRNA, with no significant difference in expression among
      them. Western blot analyses demonstrated the presence of the bovine OXTR protein
      at about 45 kDa in lymphocytes, as well as expression of the 14-kDa precursor of
      OXT. When lymphocytes were treated with OXT, intracellular concentrations of
      calcium ([Ca2+]i) were rapidly and dramatically increased. This study
      demonstrated that bovine lymphocytes express OXTRs and that this expression can
      be regulated in a steroid-dependent manner. Furthermore, OXT elicited a
      functional [Ca2+]i response in T lymphocytes, supporting the possibility that OXT
      within the CL could act as a paracrine or autocrine regulator of resident T
      lymphocytes.

PMID- 18094353
TI  - Follicle-stimulating hormone affects spermatogonial survival by regulating the
      intrinsic apoptotic pathway in adult rats.
AB  - Follicle-stimulating hormone plays a key role in spermatogonial development in
      adult rats via poorly understood mechanisms. We aimed to identify the role of
      this hormone in the regulation of germ cell apoptosis and proliferation in adult
      rats by suppression of FSH action following passive immunoneutralization with a
      rat FSH antibody for 4 and 7 days. Apoptosis and proliferation were identified by
      TUNEL and proliferating cell nuclear antigen labeling methods, respectively.
      Intrinsic and extrinsic apoptotic pathways were identified by
      immunohistochemistry, stereological techniques, and RT-PCR by assessing pathway
      specific proteins and genes. Following FSH suppression for 4 and 7 days, we have
      previously reported a 30% decrease in spermatogonial number, with increased
      apoptosis in a stage-specific manner. The present study also shows stage-specific
      increases in apoptosis with no changes in proliferation. This increase in
      apoptosis was attributable to an increase in spermatogonial apoptosis via the
      intrinsic rather than extrinsic pathway, as shown by increased activated caspase
      9-positive spermatogonia. The concomitant suppression of FSH and LH/testosterone
      showed that testosterone alone or together with FSH was more important in
      spermatocyte and spermatid survival by regulating both apoptotic pathways. A
      reduction in the level of the intrinsic pathway transcript Bcl2l2 (apoptosis
      suppressor gene) following FSH suppression for 4 days shows that FSH regulates
      some components of the intrinsic pathway. This study reveals that FSH
      predominantly acts as a survival factor for spermatogonia by regulating the
      intrinsic pathway while having no affect on germ cell proliferation in rats in
      vivo.

PMID- 18094354
TI  - Developmental programming: deficits in reproductive hormone dynamics and
      ovulatory outcomes in prenatal, testosterone-treated sheep.
AB  - Prenatal testosterone excess leads to neuroendocrine, ovarian, and metabolic
      disruptions, culminating in reproductive phenotypes mimicking that of women with
      polycystic ovary syndrome (PCOS). The objective of this study was to determine
      the consequences of prenatal testosterone treatment on periovulatory hormonal
      dynamics and ovulatory outcomes. To generate prenatal testosterone-treated
      females, pregnant sheep were injected intramuscularly (days 30-90 of gestation,
      term=147 days) with 100 mg of testosterone-propionate in cottonseed oil semi
      weekly. Female offspring born to untreated control females and prenatal
      testosterone-treated females were then studied during their first two breeding
      seasons. Sheep were given two injections of prostaglandin F2alpha 11 days apart,
      and blood samples were collected at 2-h intervals for 120 h, 10-min intervals for
      8 h during the luteal phase (first breeding season only), and daily for an
      additional 15 days to characterize changes in reproductive hormonal dynamics.
      During the first breeding season, prenatal testosterone-treated females
      manifested disruptions in the timing and magnitude of primary gonadotropin
      surges, luteal defects, and reduced responsiveness to progesterone negative
      feedback. Disruptions in the periovulatory sequence of events during the second
      breeding season included: 1) delayed but increased preovulatory estradiol rise,
      2) delayed and severely reduced primary gonadotropin surge in prenatal
      testosterone-treated females having an LH surge, 3) tendency for an amplified
      secondary FSH surge and a shift in the relative balance of FSH regulatory
      proteins, and 4) luteal responses that ranged from normal to anovulatory. These
      outcomes are likely to be of relevance to developmental origin of infertility
      disorders and suggest that differences in fetal exposure or fetal susceptibility
      to testosterone may account for the variability in reproductive phenotypes.

PMID- 18094355
TI  - Long-term culture of male germline stem cells from hamster testes.
AB  - Spermatogonial stem cells provide the foundation for spermatogenesis in male
      animals. We recently succeeded in culturing and genetically engineering mouse
      spermatogonial stem cells, but little is known regarding the culture and growth
      requirements of spermatogonial stem cells in other animal species. In this study,
      we report the successful long-term culture of spermatogonial stem cells from
      hamster testes. Spermatogonial stem cells were purified using an anti-ITGA6
      antibody and cultured in the presence of glial cell line-derived neurotrophic
      factor. The cells continued to proliferate for at least 1 year. During this
      period, they were genetically modified using a lentivirus and underwent
      spermatogenesis after transplantation into the testes of immunodeficient nude
      mice. However, germ cells generated in the surrogate xenogeneic recipients did
      not differentiate beyond the spermatid stage, and these round spermatids could
      not produce offspring through in vitro microinsemination. These results suggest
      that the germ cells may not have acquired characteristics necessary for fertility
      in the xenogeneic microenvironment. Nevertheless, the successful establishment of
      culture conditions conducive for hamster spermatogonial stem cell growth and
      maintenance indicates that this technique can be extended to other animal species
      in which current genetic modification techniques are impossible or inefficient.

PMID- 18094356
TI  - Regulation of maternal and fetal hemodynamics by heme oxygenase in mice.
AB  - Heme oxygenase (HMOX) regulates vascular tone and blood pressure through the
      production of carbon monoxide (CO), a vasodilator derived from the heme
      degradation pathway. During pregnancy, the maternal circulation undergoes
      significant adaptations to accommodate the hemodynamic demands of the developing
      fetus. Our objective was to investigate the role of HMOX on maternal and fetal
      hemodynamics during pregnancy in a mouse model. We measured and compared maternal
      tissue and placental HMOX activity and endogenous CO production, represented by
      excreted CO and carboxyhemoglobin levels, during pregnancy (Embryonic Days 12.5
      15.5) to nonpregnant controls. Micro-ultrasound was used to monitor maternal
      abdominal aorta diameters as well as blood flow velocities and diameters of fetal
      umbilical arteries. Tin mesoporphyrin, a potent HMOX inhibitor, was used to
      inhibit HMOX activity. Changes in maternal vascular tone were monitored by tail
      cuff blood pressure measurements. Effects of HMOX inhibition on placental
      structures were assessed by histology. We showed that maternal tissue and
      placental HMOX activity and CO production were significantly elevated during
      pregnancy. When HMOX in the placenta was inhibited, maternal and fetal
      hemodynamics underwent significant changes, with maternal blood pressures
      increasing. We concluded that increases in maternal tissue and placental HMOX
      activity contribute to the regulation of peripheral vascular resistance and
      therefore are important for the maintenance of normal maternal vascular tone and
      fetal hemodynamic functions during pregnancy.

PMID- 18094357
TI  - Successful artificial insemination in the koala (Phascolarctos cinereus) using
      extended and extended-chilled semen collected by electroejaculation.
AB  - Artificial insemination in the koala using chilled, electroejaculated semen
      provides for a marked improvement in the reproductive and genetic management of
      captive koala colonies in Australia and internationally, and makes available the
      option of using semen collected from wild populations to expand restricted gene
      pools. Dilution of koala semen for artificial insemination is complicated because
      koalas are induced ovulators, and it is thought that ovulating factors are
      present in the semen, so that semen extension for preservation purposes might be
      anticipated to result in a failure to induce ovulation. The first two experiments
      of this study were designed to determine whether artificial insemination using
      undiluted, extended, and extended-chilled semen collected by electroejaculation
      was capable of inducing a luteal phase and/or the production of pouch young. In
      Experiment 1, 1 ml undiluted electroejaculated semen, 2 ml diluted (1:1) semen,
      and 1 ml diluted (1:1) semen resulted in seven of nine, six of nine, and six of
      nine koalas showing a luteal phase, respectively; four pouch young were produced
      in each treatment. A second artificial insemination experiment was conducted in
      which 2 ml diluted (1:1) semen was administered in three groups of nine koalas.
      The first group received semen that had been collected and diluted immediately
      without chilling, the second group was deposited with semen stored chilled for 24
      h, and the final group received semen that had been chilled for 72 h. In the
      first group, five females had a luteal phase, but none became pregnant. In group
      2, two of the five females that had a luteal phase gave birth, whereas in group
      3, four of the six females that had a luteal phase produced pouch young. In
      addition, experiment 3 was conducted to determine whether it was possible to
      produce pouch young by naturally mating koalas that were in the latter stages of
      their behavioral estrus; this information is important to the logistics of
      transporting koala semen for artificial insemination by establishing the maximum
      time frame in which females might be expected to shed a fertile oocyte. Of the 12
      females mated on Day 8 of estrus, 6 gave birth, whereas only 3 of the 10 females
      naturally mated on Day 10 of estrus produced pouch young. The majority of females
      (21 of 22) in experiment 3 showed evidence of a luteal phase. Together, these
      experiments have shown that it is possible to use undiluted, extended, or
      extended-chilled semen to produce koala offspring up to Day 8 of estrus at
      conception rates similar to those achieved following natural mating. These
      findings represent a significant advancement in the use of reproductive
      technology in marsupials and provide the basis for the shipment of koala semen
      over long distances. The pouch young produced in this study represent the first
      marsupials born following artificial insemination of extended-chilled semen and
      bring the total number of koalas produced by artificial insemination to 31.

PMID- 18094358
TI  - Gonadotropin-releasing hormone stimulates prolactin release from lactotrophs in
      photoperiodic species through a gonadotropin-independent mechanism.
AB  - Previous studies have provided evidence for a paracrine interaction between
      pituitary gonadotrophs and lactotrophs. Here, we show that GnRH is able to
      stimulate prolactin (PRL) release in ovine primary pituitary cultures. This
      effect was observed during the breeding season (BS), but not during the
      nonbreeding season (NBS), and was abolished by the application of bromocriptine,
      a specific dopamine agonist. Interestingly, GnRH gained the ability to stimulate
      PRL release in NBS cultures following treatment with bromocriptine. In contrast,
      thyrotropin-releasing hormone, a potent secretagogue of PRL, stimulated PRL
      release during both the BS and NBS and significantly enhanced the PRL response to
      GnRH during the BS. These results provide evidence for a photoperiodically
      modulated functional interaction between the GnRH/gonadotropic and prolactin axes
      in the pituitary gland of a short day breeder. Moreover, the stimulation of PRL
      release by GnRH was shown not to be mediated by the gonadotropins, since
      immunocytochemical, Western blotting, and PCR studies failed to detect pituitary
      LH or FSH receptor protein and mRNA expressions. Similarly, no gonadotropin
      receptor expression was observed in the pituitary gland of the horse, a long day
      breeder. In contrast, S100 protein, a marker of folliculostellate cells, which
      are known to participate in paracrine mechanisms within this tissue, was detected
      throughout the pituitaries of both these seasonal breeders. Therefore, an
      alternative gonadotroph secretory product, a direct effect of GnRH on the
      lactotroph, or another cell type, such as the folliculostellate cell, may be
      involved in the PRL response to GnRH in these species.

PMID- 18094359
TI  - Fbxw15/Fbxo12J is an F-box protein-encoding gene selectively expressed in oocytes
      of the mouse ovary.
AB  - In recent years, several factors required for follicular assembly and/or early
      growth of newly formed primordial follicles have been characterized, but
      additional factors likely remain to be identified. We have used cDNA arrays to
      compare gene expression in the neonatal mouse ovary at 48 h (when primordial
      follicles are being assembled) and at 96 h (when early follicular growth is
      taking place) after birth to that of ovaries collected <24 h after birth (when
      follicles have not yet been formed). Segregating genes according to their pattern
      of expression revealed the presence of one cluster of 24 genes for which
      expression consistently increased at 48 and 96 h. The top increaser in this
      cluster encodes a approximately 1.5-kb mRNA containing an open reading frame of
      1401 bp that encodes a protein of 466 amino acids. The predicted 52.3-kDa protein
      is a member of the F-box-only (FBXO) protein family, termed FBXW15 or FBXO12J. It
      has a cytoplasmic localization that includes the endoplasmic reticulum.
      Expression of Fbxw15/Fbxp12J mRNA is oocyte-specific; the mRNA is first detected
      on Gestational Day 18, decreasing thereafter to minimal levels on the day of
      birth. The prevalence of Fbxw15/Fbxp12J mRNA increases again at 48 and 96 h after
      birth, coinciding with the time of follicular assembly and the initiation of
      early follicular growth, respectively. The specific expression of Fbxw15/Fbxp12J
      in oocytes and its developmental pattern of expression suggest a role for this
      gene in the regulation of oocyte physiology.

PMID- 18094360
TI  - Ca2+ homeostasis regulates Xenopus oocyte maturation.
AB  - In contrast to the well-defined role of Ca2+ signals during mitosis, the
      contribution of Ca2+ signaling to meiosis progression is controversial, despite
      several decades of investigating the role of Ca2+ and its effectors in vertebrate
      oocyte maturation. We have previously shown that during Xenopus oocyte
      maturation, Ca2+ signals are dispensable for entry into meiosis and for germinal
      vesicle breakdown. However, normal Ca2+ homeostasis is essential for completion
      of meiosis I and extrusion of the first polar body. In this study, we test the
      contribution of several downstream effectors in mediating the Ca2+ effects during
      oocyte maturation. We show that calmodulin and calcium-calmodulin-dependent
      protein kinase II (CAMK2) are not critical downstream Ca2+ effectors during
      meiotic maturation. In contrast, accumulation of Aurora kinase A (AURKA) protein
      is disrupted in cells deprived of Ca2+ signals. Since AURKA is required for
      bipolar spindle formation, failure to accumulate AURKA may contribute to the
      defective spindle phenotype following Ca2+ deprivation. These findings argue that
      Ca2+ homeostasis is important in establishing the oocyte's competence to undergo
      maturation in preparation for fertilization and embryonic development.

PMID- 18094361
TI  - Developmental programming: impact of prenatal testosterone excess on pre- and
      postnatal gonadotropin regulation in sheep.
AB  - The goal of this study was to explore mechanisms that mediate hypersecretion of
      LH and progressive loss of cyclicity in female sheep exposed during fetal life to
      excess testosterone. Our working hypothesis was that prenatal testosterone
      excess, by its androgenic action, amplifies GnRH-induced LH (but not FSH)
      secretion and, thus, hypersecretion of LH in adulthood, and that this results
      from altered developmental gene expression of GnRH and estradiol (E2) receptors,
      gonadotropin subunits, and paracrine factors that differentially regulate LH and
      FSH synthesis. We observed that, relative to controls, females exposed during
      fetal life to excess testosterone, as well as the nor-aromatizable androgen
      dihydrotestosterone, exhibited enhanced LH but not FSH responses to intermittent
      delivery of GnRH boluses under conditions in which endogenous LH (GnRH) pulses
      were suppressed. Luteinizing hormone hypersecretion was more evident in adults
      than in prepubertal females, and it was associated with development of
      acyclicity. Measurement of pituitary mRNA concentrations revealed that prenatal
      testosterone excess induced developmental changes in gene expression of pituitary
      GnRH and E2 receptors and paracrine modulators of LH and FSH synthesis in a
      manner consistent with subsequent amplification of LH release. Together, this
      series of studies suggests that prenatal testosterone excess, by its androgenic
      action, amplifies GnRH-induced LH response, leading to LH hypersecretion and
      acyclicity in adulthood, and that this programming involves developmental changes
      in expression of pituitary genes involved in LH and FSH release.

PMID- 18094362
TI  - Dimeric transferrin inhibits phagocytosis of residual bodies by testicular rat
      Sertoli cells.
AB  - Transferrin is well known as an iron transport glycoprotein. Dimeric or
      tetrameric transferrin forms have recently been reported to modulate phagocytosis
      by human leukocytes. It is mainly synthesized by the liver, and also by other
      sources, such as Sertoli cells of the testis. Sertoli cells show a strong
      phagocytic activity toward apoptotic germ cells and residual bodies. Here, we
      provide evidence that purified human dimeric transferrin from commercial sources
      decreased residual body phagocytosis, unlike monomeric transferrin. The presence
      of iron appeared essential for dimeric transferrin inhibitory activity.
      Importantly, dimeric transferrin could be visualized by immunoblotting in Sertoli
      cell lysates as well as in culture media, indicating that dimeric transferrin
      could be physiologically secreted by Sertoli cells. By siRNA-mediated knockdown,
      we show that endogenous transferrin significantly inhibited residual body
      ingestion by Sertoli cells. These results are the first to identify dimeric
      transferrin in Sertoli cells and to demonstrate its implication as a
      physiological modulator of residual body phagocytosis by Sertoli cells.

PMID- 18094363
TI  - Adrenomedullin in the rat testis. I: Its production, actions on testosterone
      secretion, regulation by human chorionic gonadotropin, and its interaction with
      endothelin 1 in the leydig cell.
AB  - Based on the finding of gene expression of adrenomedullin (Adm) and its receptor
      components in the rat testis, a paracrine effect of ADM on testicular
      steroidogenesis has been suggested by our group. The present study demonstrates
      the gene expression of Adm and the effect of ADM on testosterone production in
      the Leydig cell. The regulation of ADM by hCG and its interaction with endothelin
      1 (EDN1) in the rat Leydig cells are also observed. Primary culture of Leydig
      cells produced Adm mRNA and secreted 275+/-19 pg immunoreactive ADM per 10(6)
      cells in 24 h. In addition, the Leydig cell was shown to coexpress mRNAs encoding
      for the calcitonin receptor-like receptor (CALCRL) and receptor activity
      modifying protein (RAMP1, RAMP2, and RAMP3). These may account for the specific
      binding of ADM to the Leydig cells. Administration of ADM to Leydig cells
      resulted in an inhibition of hCG- and EDN1-stimulated testosterone production.
      Correlated with this, ADM reduced EDN1 production, whereas its production was
      increased by EDN1. Furthermore, the production of ADM and the mRNA levels of
      Calcrl and Ramp2 were suppressed by hCG. Our results suggest that ADM has an
      autocrine effect on Leydig cell steroidogenesis, possibly by interacting with
      EDN1 and under the control of gonadotropin. We propose that there is an ADM/EDN1
      local regulatory mechanism that may be important in modulating the control of
      testicular functions by gonadotropins.

PMID- 18094364
TI  - Adrenomedullin in the rat testis. II: Its production, actions on inhibin
      secretion, regulation by follicle-stimulating hormone, and its interaction with
      endothelin 1 in the Sertoli cell.
AB  - The present study demonstrates the expression of adrenomedullin (ADM) in the rat
      Sertoli cells and its effect on inhibin production. The regulation of ADM by FSH
      and its interaction with endothelin 1 (EDN1) in the rat Sertoli cells have also
      been established. Primary culture of Sertoli cells secreted 414+/-27 pg
      immunoreactive ADM per 10(6) cells in 24 h and expressed Adm mRNA. In addition,
      the Sertoli cell was shown to co-express mRNAs encoding for the calcitonin
      receptor-like receptor (CALCRL) and receptor activity-modifying proteins (RAMPs)
      1-3. These may account for the specific binding of ADM to the Sertoli cells.
      Administration of ADM to Sertoli cells resulted in an enhancement of basal and
      FSH-stimulated inhibin B production. On the other hand, the production of ADM and
      the mRNA levels of Calcrl and Ramp2 in the Sertoli cells were suppressed by FSH.
      The results suggest that ADM, via its control in the secretion of inhibin B, may
      play a role in regulating spermatogenesis as well as the hypothalamus-pituitary
      gonad feedback system. In addition, like in the Leydig cell, ADM and EDN1 were
      found to regulate the production of each other in opposite directions in the
      Sertoli cells, suggesting the presence of yet another local regulatory mechanism
      in the rat testis that may be important in modulating testicular functions
      regulated by gonadotropins.

PMID- 18094365
TI  - Mechanisms of vascular calcification in chronic kidney disease.
AB  - Vascular calcification is common in chronic kidney disease and associated with
      increased morbidity and mortality. Its mechanism is multifactorial and
      incompletely understood. Patients with chronic kidney disease are at risk for
      vascular calcification because of multiple risk factors that induce vascular
      smooth muscle cells to change into a chondrocyte or osteoblast-like cell; high
      total body burden of calcium and phosphorus due to abnormal bone metabolism; low
      levels of circulating and locally produced inhibitors; impaired renal excretion;
      and current therapies. Together these factors increase risk and complicate the
      management of vascular calcification.

PMID- 18094366
TI  - Obesity impacts access to kidney transplantation.
AB  - Current billing practices and mandates to report surgical outcomes are
      disincentives to surgical treatment of obese patients, who are at increased risk
      for longer hospital stays and higher complication rates. The objective of this
      study was to quantify the independent association between body mass index (BMI)
      and waiting time for kidney transplantation to identify potential provider bias
      against surgical treatment of the obese. A secondary data analysis was performed
      of a prospective cohort of 132,353 patients who were registered for kidney
      transplantation in the United States between 1995 and 2006. Among all patients
      awaiting kidney transplantation, the likelihood of receiving a transplant
      decreased with increasing degree of obesity, categorized by ranges of BMI
      (adjusted hazard ratios 0.96 for overweight, 0.93 for obese, 0.72 for severely
      obese, and 0.56 for morbidly obese, compared with a reference group of patients
      with normal BMI). Similarly, the likelihood of being bypassed when an organ
      became available increased in a graded manner with category of obesity (adjusted
      incidence rate ratio 1.02 for overweight, 1.05 for obese, 1.11 for severely
      obese, and 1.22 for morbidly obese). Although matching an available organ with an
      appropriate recipient requires clinical judgment, which could not be fully
      captured in this study, the observed differences are dramatic and warrant further
      studies to understand this effect better and to design a system that is less
      susceptible to unintended bias.

PMID- 18094367
TI  - Roles of ERK and cPLA2 in the angiotensin II-mediated biphasic regulation of Na+
      HCO3(-) transport.
AB  - Regulation of renal proximal transport by angiotensin II (Ang II) is biphasic:
      low concentrations (picomolar to nanomolar) stimulate reabsorption, but higher
      concentrations (nanomolar to micromolar) inhibit reabsorption. Traditionally, the
      stimulatory effect has been attributed to activation of protein kinase C and/or a
      decrease in intracellular cAMP, whereas the inhibitory action has been attributed
      to the activation of phospholipase A2 (PLA2) and the subsequent release of
      arachidonic acid. The Ang II receptor subtype responsible for these effects and
      the intracellular signaling pathways involved are not completely understood. We
      isolated proximal tubules from wild-type, Ang II type 1A receptor (AT1A)
      deficient, and group IVA cytosolic phospholipase A2 (cPLA2alpha)-deficient mice,
      and compared their responses to Ang II. In wild-type mice, we found that the
      stimulatory and inhibitory effects of Ang II on Na+-HCO3(-) cotransporter
      activity are both AT1-mediated but that ERK activation only plays a role in the
      former. The stimulatory effect of Ang II was also observed in AT1A-deficient
      mice, suggesting that this occurs through AT1B. In contrast, the inhibitory
      effects of Ang II appeared to be mediated by cPLA2alpha activation because high
      concentration Ang II stimulated Na+-HCO3(-) cotransporter activity when
      cPLA2alpha activity was abrogated by pharmacological means or genetic knockout.
      Consistent with this observation, we found that activation of the cPLA2alpha/P450
      pathway suppressed ERK activation. We conclude that Ang II activates ERK and
      cPLA2alpha in a concentration-dependent manner via AT1, and that the balance
      between ERK and cPLA2alpha activities determines the ultimate response to Ang II
      in intact proximal tubules.

PMID- 18094368
TI  - Peritubular ischemia contributes more to tubular damage than proteinuria in
      immune-mediated glomerulonephritis.

PMID- 18094370
TI  - Images in clinical medicine. Chronic budd-Chiari syndrome and abdominal varices.

PMID- 18094369
TI  - Evaluation of 1p36 markers and clinical outcome in a skull base chordoma study.
AB  - Chordomas are rare embryogenetic tumors, arising from remnants of the notochord,
      characterized by local invasiveness and variable tendency for recurrence. No
      molecular markers are currently used in a clinical setting to distinguish
      chordomas with an indolent or an aggressive pattern. Among the genetic lesions
      observed in this tumor, one of the most commonly detected is 1p loss. In a
      previous study we observed 1p36 loss of heterozygosity (LOH) in 85% of the
      analyzed chordomas. We studied a group of 16 homogeneously treated skull base
      chordomas (SBCs), reporting 1p36 LOH in 75% of them and determining the
      expression pattern of eight apoptotic genes mapped at 1p36. No tumors shared a
      common expression profile with nucleus pulposus, which is considered the only
      adult normal tissue deriving from notochord. In particular, tumor necrosis factor
      receptor superfamily genes TNFRSF8, TNFRSF9, and TNFRSF14 were differently
      expressed compared with control in a higher percentage of tumors (40%-53%) than
      were the remaining analyzed genes, suggesting that the deregulation of these
      three genes might have a role in chordoma tumorigenesis. The presence/absence of
      LOH and the expression/nonexpression of each apoptotic gene were studied in a
      survival analysis. Our results suggest that the lack of 1p36 LOH or the presence
      of TNFRSF8 expression might be associated with a better prognosis in patients
      with SBCs.

PMID- 18094371
TI  - The view from the other side--patients, doctors, and the power of a camera.

PMID- 18094372
TI  - The good patient.

PMID- 18094373
TI  - Stromal effects in breast cancer.

PMID- 18094374
TI  - p53--master and commander.

PMID- 18094375
TI  - Breast-cancer stromal cells with TP53 mutations and nodal metastases.
AB  - BACKGROUND: The importance of cross-talk between a cancer and its
      microenvironment has been increasingly recognized. We hypothesized that
      mutational inactivation of the tumor-suppressor gene TP53 and genomic alterations
      in stromal cells of a tumor's microenvironment contribute to the clinical
      outcome. METHODS: We performed TP53 mutation analysis and genomewide analysis of
      loss of heterozygosity and allelic imbalance on DNA from isolated neoplastic
      epithelial and stromal cells from 43 patients with hereditary breast cancer and
      175 patients with sporadic breast cancer. Compartment-specific patterns and TP53
      mutations were analyzed. Associations between compartment-specific TP53 status,
      loss of heterozygosity or allelic imbalance, and clinical and pathological
      characteristics were computed. RESULTS: TP53 mutations were associated with an
      increased loss of heterozygosity and allelic imbalance in both hereditary and
      sporadic breast cancers, but samples from patients with hereditary disease had
      more frequent mutations than did those from patients with sporadic tumors (74.4%
      vs. 42.3%, P=0.001). Only 1 microsatellite locus (2p25.1) in stromal cells from
      hereditary breast cancers was associated with mutated TP53, whereas there were 66
      such loci in cells from sporadic breast cancers. Somatic TP53 mutations in
      stroma, but not epithelium, of sporadic breast cancers were associated with
      regional nodal metastases (P=0.003). A specific set of five loci linked to an
      increased loss of heterozygosity and allelic imbalance in the stroma of sporadic
      tumors was associated with nodal metastases in the absence of TP53 mutations. No
      associations were found between any of the clinical or pathological features of
      hereditary breast cancer with somatic TP53 mutations. CONCLUSIONS: Stroma
      specific loss of heterozygosity or allelic imbalance is associated with somatic
      TP53 mutations and regional lymph-node metastases in sporadic breast cancer but
      not in hereditary breast cancer.

PMID- 18094376
TI  - TP53 mutations and survival in squamous-cell carcinoma of the head and neck.
AB  - BACKGROUND: The abrogation of function of the tumor-suppressor protein p53 as a
      result of mutation of its gene, TP53, is one of the most common genetic
      alterations in cancer cells. We evaluated TP53 mutations and survival in patients
      with squamous-cell carcinoma of the head and neck. METHODS: A total of 560
      patients with squamous-cell carcinoma of the head and neck who were treated
      surgically with curative intent were enrolled in our prospective multicenter, 7
      year study. TP53 mutations were analyzed in DNA from the tumor specimens with the
      use of the Affymetrix p53 chip and the Surveyor DNA endonuclease and denaturing
      high-performance liquid chromatography. Mutations were classified into two
      groups, disruptive and nondisruptive, according to the degree of disturbance of
      protein structure predicted from the crystal structure of the p53-DNA complexes.
      TP53 mutational status was compared with clinical outcome. RESULTS: TP53
      mutations were found in tumors from 224 of 420 patients (53.3%). As compared with
      wild-type TP53, the presence of any TP53 mutation was associated with decreased
      overall survival (hazard ratio for death, 1.4; 95% confidence interval [CI], 1.1
      to 1.8; P=0.009), with an even stronger association with disruptive mutations
      (hazard ratio, 1.7; 95% CI, 1.3 to 2.4; P<0.001) and no significant association
      with nondisruptive mutations (hazard ratio, 1.2; 95% CI, 0.9 to 1.7; P=0.16). In
      multivariate analyses a disruptive TP53 alteration, as compared with the absence
      of a TP53 mutation, had an independent, significant association with decreased
      survival (hazard ratio, 1.7; 95% CI, 1.2 to 2.4; P=0.003). CONCLUSIONS:
      Disruptive TP53 mutations in tumor DNA are associated with reduced survival after
      surgical treatment of squamous-cell carcinoma of the head and neck.

PMID- 18094377
TI  - Reduced exposure to calcineurin inhibitors in renal transplantation.
AB  - BACKGROUND: Immunosuppressive regimens with the fewest possible toxic effects are
      desirable for transplant recipients. This study evaluated the efficacy and
      relative toxic effects of four immunosuppressive regimens. METHODS: We randomly
      assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine,
      mycophenolate mofetil, and corticosteroids, or daclizumab induction,
      mycophenolate mofetil, and corticosteroids in combination with low-dose
      cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point
      was the estimated glomerular filtration rate (GFR), as calculated by the
      Cockcroft-Gault formula, 12 months after transplantation. Secondary end points
      included acute rejection and allograft survival. RESULTS: The mean calculated GFR
      was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in
      the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy
      proven acute rejection was lower in patients receiving low-dose tacrolimus
      (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose
      cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed
      significantly among the four groups (P=0.02) and was highest in the low-dose
      tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%),
      the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group
      (89.3%). Serious adverse events were more common in the low-dose sirolimus group
      than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar
      proportion of patients in each group had at least one adverse event during
      treatment (86.3 to 90.5%). CONCLUSIONS: A regimen of daclizumab, mycophenolate
      mofetil, and corticosteroids in combination with low-dose tacrolimus may be
      advantageous for renal function, allograft survival, and acute rejection rates,
      as compared with regimens containing daclizumab induction plus either low-dose
      cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without
      induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].).

PMID- 18094378
TI  - Telbivudine versus lamivudine in patients with chronic hepatitis B.
AB  - BACKGROUND: Reducing hepatitis B virus (HBV) replication to minimal levels is
      emerging as a key therapeutic goal for chronic hepatitis B. METHODS: In this
      double-blind, phase 3 trial, 1370 patients with chronic hepatitis B were randomly
      assigned to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. The
      primary efficacy end point was noninferiority of telbivudine to lamivudine for
      therapeutic response (i.e., a reduction in serum HBV DNA levels to fewer than 5
      log10 copies per milliliter, along with loss of hepatitis B e antigen [HBeAg] or
      normalization of alanine aminotransferase levels). Secondary efficacy measures
      included histologic response, changes in serum HBV DNA levels, and HBeAg
      responses. RESULTS: At week 52, a significantly higher proportion of HBeAg
      positive patients receiving telbivudine than of those receiving lamivudine had a
      therapeutic response (75.3% vs. 67.0%, P=0.005) or a histologic response (64.7%
      vs. 56.3%, P=0.01); telbivudine also was not inferior to lamivudine for these end
      points in HBeAg-negative patients. In HBeAg-positive and HBeAg-negative patients,
      telbivudine was superior to lamivudine with respect to the mean reduction in the
      number of copies of HBV DNA from baseline, the proportion of patients with a
      reduction in HBV DNA to levels undetectable by polymerase-chain-reaction assay,
      and development of resistance to the drug. Elevated creatine kinase levels were
      more common in patients who received telbivudine, whereas elevated alanine
      aminotransferase and aspartate aminotransferase levels were more common in those
      who received lamivudine. CONCLUSIONS: Among patients with HBeAg-positive chronic
      hepatitis B, the rates of therapeutic and histologic response at 1 year were
      significantly higher in patients treated with telbivudine than in patients
      treated with lamivudine. In both the HBeAg-negative and the HBeAg-positive
      groups, telbivudine demonstrated greater HBV DNA suppression with less resistance
      than did lamivudine. (ClinicalTrials.gov number, NCT00057265
      [ClinicalTrials.gov].).

PMID- 18094379
TI  - Outcomes of care by hospitalists, general internists, and family physicians.
AB  - BACKGROUND: The hospitalist model is rapidly altering the landscape for inpatient
      care in the United States, yet evidence about the clinical and economic outcomes
      of care by hospitalists is derived from a small number of single-hospital studies
      examining the practices of a few physicians. METHODS: We conducted a
      retrospective cohort study of 76,926 patients 18 years of age or older who were
      hospitalized between September 2002 and June 2005 for pneumonia, heart failure,
      chest pain, ischemic stroke, urinary tract infection, acute exacerbation of
      chronic obstructive pulmonary disease, or acute myocardial infarction at 45
      hospitals throughout the United States. We used multivariable models to compare
      the outcomes of care by 284 hospitalists, 993 general internists, and 971 family
      physicians. RESULTS: As compared with patients cared for by general internists,
      patients cared for by hospitalists had a modestly shorter hospital stay (adjusted
      difference, 0.4 day; P<0.001) and lower costs (adjusted difference, $268; P=0.02)
      but a similar inpatient rate of death (odds ratio, 0.95; 95% confidence interval
      [CI], 0.85 to 1.05) and 14-day readmission rate (odds ratio, 0.98; 95% CI, 0.91
      to 1.05). As compared with patients cared for by family physicians, patients
      cared for by hospitalists had a shorter length of stay (adjusted difference, 0.4
      day; P<0.001), and the costs (adjusted difference, $125; P=0.33), rate of death
      (odds ratio, 0.95; 95% CI, 0.83 to 1.07), and 14-day readmission rate (odds
      ratio, 0.95; 95% CI, 0.87 to 1.04) were similar. CONCLUSIONS: For common
      inpatient diagnoses, the hospitalist model is associated with a small reduction
      in the length of stay without an adverse effect on rates of death or readmission.
      Hospitalist care appears to be modestly less expensive than that provided by
      general internists, but it offers no significant savings as compared with the
      care provided by family physicians.

PMID- 18094380
TI  - Infection in solid-organ transplant recipients.

PMID- 18094381
TI  - Images in clinical medicine. Calcinosis associated with renal failure.

PMID- 18094382
TI  - Case records of the Massachusetts General Hospital. Case 39-2007. A 5-month-old
      girl with skin lesions.

PMID- 18094383
TI  - Balancing efficacy and toxicity in kidney-transplant immunosuppression.

PMID- 18094384
TI  - The hospitalist movement--time to move on.

PMID- 18094385
TI  - Small RNAs and large DNA viruses.

PMID- 18094386
TI  - Bariatric surgery and mortality.

PMID- 18094387
TI  - Saline or albumin for fluid resuscitation in traumatic brain injury.

PMID- 18094388
TI  - Gynecomastia.

PMID- 18094389
TI  - Reversal of pacing-induced heart failure by left ventricular apical pacing.

PMID- 18094390
TI  - A lifetime pacemaker revisited.

PMID- 18094391
TI  - The balance between PGD synthase and PGE synthase is a major determinant of
      atherosclerotic plaque instability in humans.

PMID- 18094392
TI  - Choice of anticoagulant critically affects measurement of circulating platelet
      leukocyte complexes.

PMID- 18094393
TI  - Protective signaling pathways of activated protein C in endothelial cells.

PMID- 18094394
TI  - Angiotensin II and new vessel formation: aiming for the right oxidative window.

PMID- 18094395
TI  - Phagocytes of the transected feline optic nerve: an ultrastructural study.
AB  - Following eye enucleation, there is a spatio-temporal pattern of degeneration
      along the length of the feline optic nerve, and this depends on the proximity of
      the segment or zone to the transected end. Thus, the rate of axonal degeneration
      depends on how close it is to the point of excision of the eye. In the proximal
      and medial segments, degeneration is rapid and the phagocytes originate from
      extrinsic haematogenous cells, which have invaded the optic nerve from
      surrounding meningeal blood vessels and capillaries. These phagocytes appear
      initially around blood vessels and then progressively spread to the parenchyma.
      In the distal segments, where Wallerian degeneration has occurred, the
      corresponding process is relatively slow and the phagocytes originate
      intrinsically. In contrast, these phagocytes are first seen in the parenchyma and
      then later spread to the blood vessels. Ultrastructurally, these phagocytes share
      fine features specifically identified with neuroglial cells such as microglia,
      oligodendrocytes but not astrocytes. For example, these phagocytes are rich in
      organelles such as mitochondria, ribosomes, microtubules, and rough and smooth
      endoplasmic reticulum including the Golgi apparatus. Cytoplasmic inclusions such
      as dense laminar bodies, lipid droplets, lysosomes and lipofuscin granules are
      also present. Intermediate filaments, seen only in astrocytes, are not found in
      these phagocytes. Although the study has established that the phagocytes are
      intrinsic and neuroglial in origin, their true identity is still unresolved.
      Secondarily, the study has shown that oligodendrocytes continue to survive and
      remain viable in an axon-free environment. The question about their new role in
      Wallerian degeneration remains.

PMID- 18094396
TI  - Temporal occurrence of immature skeletal muscle fibers in the sciatic nerve
      matrix regenerating within the silicone chamber after nerve transection in the
      normal rat.
AB  - We examined by light and electron microscopy the immature skeletal muscle fibers
      in the rat sciatic nerve regenerating within the silicone chamber 14 days after
      nerve transection. Small myelinated and nonmyelinated nerve fibers associated
      with Schwann cells from the proximal stump began to approach the midportion of
      the interstump zone. In the middle segment, fibroblasts or fibroblast-like
      mesenchymal cells and macrophages were observed everywhere in the newly formed
      matrix filled with exuded erythrocytes and fibrin clots. In addition to some
      fibroblast-like mesenchymal cells were closely apposed to each other. However,
      the proximal and distal segments contained immature muscle fibers with various
      amount of myofilaments and one or plural centrally located nuclei, thus
      indicating various phases of the early differentiation of skeletal muscle fibers
      similar to those observed during an early stage of developing muscle fibers.
      However, the precise origin of these skeletal muscle fibers remains to be
      determined.

PMID- 18094397
TI  - Quantitative evaluation of sebum lipid components with nuclear magnetic
      resonance.
AB  - A NMR spectroscopic method is described that enables the quantitation of specific
      lipid classes and components, independent of fatty acid composition. We
      demonstrate this method for measuring cholesterol, squalene, and pools of sterol
      esters, wax esters (WEs), and triglyceride (TG) components in sebum and meibum.
      When 600 MHz NMR equipment is used in conjunction with highly sensitive
      cryogenically cooled probes, this method has adequate sensitivity, and for some
      applications, advantages over commonly used HPLC-evaporative light-scattering
      detection and mass spectrometry-based approaches. This method is shown to be
      useful for preclinical and clinical monitoring of the efficacy of sebum-reducing
      agents in animals and humans. In Syrian hamsters, 3% topical flutamide and 20
      mg/kg oral isotretinoin reduced sterol esters by 18.7% and 30.0%, respectively,
      and reduced WEs by 32.9% and 31.8%, respectively, as measured in a punch biopsy
      of the ear. In a 72 patient clinical methodology study, the assay delivered
      reproducible and noninvasive measurements of WEs, cholesteryl esters, TGs, and
      squalene from Sebutape skin blots. The quantitative results of sebum analysis
      obtained by the NMR method correlate well with those obtained with HPLC-based
      approaches. This approach may be broadly applicable to cases in which fatty acid
      independent quantification of lipid classes is desired.

PMID- 18094398
TI  - BRCA-1 in sporadic epithelial ovarian cancer: lessons learned from the genetics
      of hereditary disease.

PMID- 18094399
TI  - The requirements for CTL-mediated rejection of cancer in humans: NKG2D and its
      role in the immune responsiveness of melanoma.

PMID- 18094400
TI  - Src continues aging: current and future clinical directions.
AB  - Aberrant activation of members of the Src family of nonreceptor protein tyrosine
      kinases is common in solid tumor malignancies and may contribute to the
      development and/or progression of these tumors. As a result, four Src inhibitors
      are now in more than 50 clinical trials for at least 14 different types of solid
      tumors. In this review, we briefly discuss the preclinical rationale for Src
      inhibitors, the development strategies most likely to be successful in the
      clinic, and the rationale for Src inhibitors in combination with other agents as
      part of a more comprehensive therapeutic strategy. As the use of Src family
      inhibitors in clinical trials on solid tumors is in its infancy, further studies
      on the roles of Src family kinases in tumor progression, chemoresistance,
      epidermal-to-mesenchymal transition, and other properties of tumor progression
      will be important in designing the most effective clinical trials using these
      inhibitors.

PMID- 18094401
TI  - Mechanisms of resistance to histone deacetylase inhibitors and their therapeutic
      implications.
AB  - Histone deacetylase inhibitors (HDI) are a promising new approach to the
      treatment of cancer. HDIs have been shown to induce differentiation, cell cycle
      arrest, and apoptosis in a variety of transformed cell lines; inhibit tumor
      growth in animal models; and show antitumor activity in clinical trials.
      Vorinostat, which has shown clinical responses in approximately 30% of patients
      with advanced cutaneous T-cell lymphoma, is the first HDI approved for the
      treatment of cancer, and it is currently being evaluated in other indications. A
      better understanding of the molecular determinants of resistance to HDIs may
      provide the basis for therapeutic combinations with improved clinical efficacy.
      Poor response to treatment could be linked to systemic factors like
      pharmacokinetics or to tumor-specific factors both at the level of the malignant
      cells (tumor intrinsic) or the tumor microenvironment. This review focuses on the
      tumor intrinsic mechanisms of drug resistance (excluding mechanism of acquired
      resistance due to chronic exposure). In particular, attention is given to
      selected mechanisms that are relevant across chemical classes of HDIs and that
      can aid in the design of rational combination strategies.

PMID- 18094402
TI  - Delta-like 4/Notch signaling and its therapeutic implications.
AB  - Intense research efforts have been focused toward the identification of
      regulators of angiogenesis and the development of antiangiogenesis-based cancer
      therapies. The approval of anti-vascular endothelial growth factor (VEGF)
      monoclonal antibody (bevacizumab) for use in colorectal and lung cancer provides
      clinical validation for targeting angiogenesis for the treatment of cancer. Delta
      like 4 (Dll4)-mediated Notch signaling represents another key pathway essential
      for vascular development. Recent studies yield substantial insights into the role
      of Dll4 in angiogenesis. Dll4 is downstream of VEGF signaling and its activation
      triggers a negative feedback that restrains the effects of VEGF. Attenuation of
      Dll4/Notch signaling results in chaotic vascular network with excessive branching
      and sprouting. In preclinical studies, blocking of Dll4/Notch signaling is
      associated with a paradoxical increase in tumor vessel density, yet causes marked
      growth inhibition due to functionally defective vasculature. Dll4 blockade holds
      promise as an additional strategy for angiogenesis-based cancer therapy,
      especially when resistance to and/or escape from existing therapies evolve.

PMID- 18094404
TI  - Targeting the cell death-survival equation.

PMID- 18094405
TI  - BCL-2 family proteins: critical checkpoints of apoptotic cell death.
AB  - Apoptosis is a morphologically distinct form of programmed cell death essential
      for normal development and tissue homeostasis. Aberrant regulation of this
      pathway is linked to multiple human diseases, including cancer, autoimmunity,
      neurodegenerative disorders, and diabetes. The BCL-2 family of proteins
      constitutes a critical control point in apoptosis residing immediately upstream
      of irreversible cellular damage, where family members control the release of
      apoptogenic factors from mitochondria. The cardinal member of this family, BCL-2,
      was originally discovered as the defining oncogene in follicular lymphomas,
      located at one reciprocal breakpoint of the t(14;18) (q32;q21) chromosomal
      translocation. Since this original discovery, remarkable efforts marshaled by
      many investigators around the world have advanced our knowledge of the basic
      biology, molecular mechanisms, and therapeutic targets in the apoptotic pathway.
      This review highlights findings from many laboratories that have helped uncover
      some of the critical control points in apoptosis. The emerging picture is that of
      an intricate cellular machinery orchestrated by tightly regulated molecular
      interactions and conformational changes within BCL-2 family proteins that
      ultimately govern the cellular commitment to apoptotic death.

PMID- 18094406
TI  - The challenge of drugging undruggable targets in cancer: lessons learned from
      targeting BCL-2 family members.
AB  - The genomic and proteomic revolutions have provided us with an ever-increasing
      number of mechanistic insights into cancer pathogenesis. Mutated genes and
      pathologic protein products have emerged as the basis for modern anticancer drug
      development. With the increasing realization of the importance of disrupting
      oncogenic protein-protein interaction, new challenges have emerged for classical
      small molecule and protein-based drug modalities, i.e., the critical need to
      target flat and extended protein surfaces. Here, we highlight two distinct
      technologies that are being used to bridge the pharmacologic gap between small
      molecules and protein therapeutics. With the BCL-2 family of survival proteins as
      their substrate for intracellular targeting, we conclude that peptide stapling
      and fragment-based drug discovery show promise to traverse the critical surface
      features of proteins that drive human cancer.

PMID- 18094407
TI  - The roles of therapy-induced autophagy and necrosis in cancer treatment.
AB  - Metabolic and therapeutic stresses activate several signal transduction pathways
      that regulate cell death and cell survival in cancer cells. Although decades of
      research unraveled the pathways that regulate apoptosis and allowed the
      development of novel diagnostic and therapeutic modalities in cancer treatment,
      only recently has the regulation and significance of tumor cell autophagy and
      necrosis become the focus of investigations. Necrosis is an irreversible
      inflammatory form of cell death. In contrast, autophagy is a reversible process
      that can contribute both to tumor cell death and survival. This review describes
      recent advances in understanding the regulation of autophagy and necrosis and
      their implications for cancer therapy. Currently available methods to measure
      autophagy and necrosis are highlighted. The effect of tumor cell autophagy and
      necrosis on host immunity is explored. Finally, therapeutic approaches that
      target autophagy and necrosis in cancer are described.

PMID- 18094408
TI  - Is cell death a critical end point for anticancer therapies or is cytostasis
      sufficient?
AB  - Since the discovery of conventional chemotherapy and the development of new
      target-based agents, the importance of cytostasis in anticancer activity has been
      debated. This review examines the relative importance of both cytostasis and
      cytotoxicity based on both preclinical data and clinical reports. Several
      limitations of our basic and clinical methods to evaluate cytostasis and
      cytotoxicity will be highlighted. Molecular mechanisms of cytostasis will be
      analyzed, including interference with the cell cycle as well as putative links
      with necrosis and autophagy. Finally, we will cite evidence that most older and
      newer compounds are both cytostatic and cytotoxic. The relative role of
      cytostasis and cytotoxicity on future drug screening and clinical development
      will be explored.

PMID- 18094409
TI  - Input of DNA microarrays to identify novel mechanisms in multiple myeloma biology
      and therapeutic applications.
AB  - Multiple myeloma is a B-cell neoplasia characterized by the proliferation of a
      clone of malignant plasma cells in the bone marrow. We review here the input of
      gene expression profiling of myeloma cells and of their tumor microenvironment to
      develop new tumor classifiers, to better understand the biology of myeloma cells,
      to identify some mechanisms of drug sensitivity and resistance, to identify new
      myeloma growth factors, and to depict the complex interactions between tumor
      cells and their microenvironment. We discuss how these findings may improve the
      clinical outcome of this still incurable disease.

PMID- 18094410
TI  - A novel set of DNA methylation markers in urine sediments for sensitive/specific
      detection of bladder cancer.
AB  - PURPOSE: This study aims to provide a better set of DNA methylation markers in
      urine sediments for sensitive and specific detection of bladder cancer.
      EXPERIMENTAL DESIGN: Fifty-nine tumor-associated genes were profiled in three
      bladder cancer cell lines, a small cohort of cancer biopsies and urine sediments
      by methylation-specific PCR. Twenty-one candidate genes were then profiled in
      urine sediments from 132 bladder cancer patients (8 cases for stage 0a; 68 cases
      for stage I; 50 cases for stage II; 4 cases for stages III; and 2 cases for stage
      IV), 23 age-matched patients with noncancerous urinary lesions, 6 neurologic
      diseases, and 7 healthy volunteers. RESULTS: Despite six incidences of four genes
      reported in 3 of 23 noncancerous urinary lesion patients analyzed, cancer
      specific hypermethylation in urine sediments were reported for 15 genes (P <
      0.05). Methylation assessment of an 11-gene set (SALL3, CFTR, ABCC6, HPR1,
      RASSF1A, MT1A, RUNX3, ITGA4, BCL2, ALX4, MYOD1, DRM, CDH13, BMP3B, CCNA1, RPRM,
      MINT1, and BRCA1) confirmed the existing diagnosis of 121 among 132 bladder
      cancer cases (sensitivity, 91.7%) with 87% accuracy. Significantly, more than 75%
      of stage 0a and 88% of stage I disease were detected, indicating its value in the
      early diagnosis of bladder cancer. Interestingly, the cluster of reported
      methylation markers used in the U.S. bladder cancers is distinctly different from
      that identified in this study, suggesting a possible epigenetic disparity between
      the American and Chinese cases. CONCLUSIONS: Methylation profiling of an 11-gene
      set in urine sediments provides a sensitive and specific detection of bladder
      cancer.

PMID- 18094411
TI  - Estrogen receptor status could modulate the genomic pattern in familial and
      sporadic breast cancer.
AB  - PURPOSE: Familial breast cancer represents 5% to 10% of all breast tumors.
      Mutations in the two known major breast cancer susceptibility genes, BRCA1 and
      BRCA2, account for a minority of familial breast cancer, whereas families without
      mutations in these genes (BRCAX group) account for 70% of familial breast cancer
      cases. EXPERIMENTAL DESIGN: To better characterize and define the genomic
      differences between the three classes of familial tumors and sporadic
      malignancies, we have analyzed 19 BRCA1, 24 BRCA2, and 31 BRCAX samples from
      familial breast cancer patients and 19 sporadic breast tumors using a 1-Mb
      resolution bacterial artificial chromosome array-based comparative genomic
      hybridization. RESULTS: We found that BRCA1/2 tumors showed a higher genomic
      instability than BRCAX and sporadic cancers. There were common genomic
      alterations present in all breast cancer groups, such as gains of 1q and 16p or
      losses of 8ptel-p12 and 16q. We found that the presence/absence of the estrogen
      receptor (ER) may play a crucial role in driving tumor development through
      distinct genomic pathways independently of the tumor type (sporadic or familial)
      and mutation status (BRCA1 or BRCA2). ER(-) tumors presented higher genomic
      instability and different altered regions than ER+ ones. CONCLUSIONS: According
      to our results, the BRCA gene mutation status (mainly BRCA1) would contribute to
      the genomic profile of abnormalities by increasing or modulating the genome
      instability.

PMID- 18094412
TI  - Angiogenesis-promoting gene patterns in alveolar soft part sarcoma.
AB  - PURPOSE: We examined a cohort of patients with alveolar soft part sarcoma (ASPS)
      treated at our institution and showed the characteristic ASPSCR1-TFE3 fusion
      transcript in their tumors. Investigation of potential angiogenesis-modulating
      molecular determinants provided mechanistic and potentially therapeutically
      relevant insight into the enhanced vascularity characteristic of this unusual
      tumor. EXPERIMENTAL DESIGN: Medical records of 71 patients with ASPS presenting
      at the University of Texas M.D. Anderson Cancer Center (1986-2005) were reviewed
      to isolate 33 patients with formalin-fixed paraffin-embedded material available
      for study. RNA extracted from available fresh-frozen and formalin-fixed paraffin
      embedded human ASPS tumors were analyzed for ASPSCR1-TFE3 fusion transcript
      expression using reverse transcription-PCR and by angiogenesis oligomicroarrays
      with immunohistochemical confirmation. RESULTS: Similar to previous studies,
      actuarial 5- and 10-year survival rates were 74% and 51%, respectively, despite
      frequent metastasis. ASPSCR1-TFE3 fusion transcripts were identified in 16 of 18
      ASPS samples. In the three frozen samples subjected to an angiogenesis
      oligoarray, 18 angiogenesis-related genes were up-regulated in tumor over
      adjacent normal tissue. Immunohistochemistry for jag-1, midkine, and angiogenin
      in 33 human ASPS samples confirmed these results. Comparison with other sarcomas
      indicates that the ASPS angiogenic signature is unique. CONCLUSION: ASPS is a
      highly vascular and metastatic tumor with a surprisingly favorable outcome;
      therapeutically resistant metastases drive mortality. Future molecular therapies
      targeting overexpressed angiogenesis-promoting proteins (such as those identified
      here) could benefit patients with ASPS.

PMID- 18094413
TI  - EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma.
AB  - PURPOSE: Angiomatoid fibrous histiocytoma (AFH) is a low-grade mesenchymal
      neoplasm which usually occurs in children and adolescents. Either FUS-ATF1 or
      EWSR1-ATF1 have been detected in the few cases published, pointing to the
      interchangeable role of FUS and EWSR1 in this entity. EWSR1-ATF1 also represents
      the most frequent genetic alteration in clear cell sarcoma, suggesting the
      existence of a molecular homology between these two histotypes. We investigated
      the presence of EWSR1-CREB1, recently found in gastrointestinal clear cell
      sarcoma, and FUS-CREB1, as well as the already reported FUS-ATF1 and EWSR1-ATF1
      in a series of AFH. EXPERIMENTAL DESIGN: Fourteen cases were analyzed by
      fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections,
      using a commercial EWSR1 probe and custom-designed probes for FUS, ATF1, and
      CREB1. In two cases, four-color FISH was also done. Reverse transcription-PCR for
      the four hypothetical fusion genes was done in one case, for which frozen
      material was available. RESULTS: Thirteen cases showed rearrangements of both
      EWSR1 and CREB1, whereas one case showed the rearrangement of both EWSR1 and
      ATF1. Four-color FISH confirmed the results in two selected cases. Reverse
      transcription-PCR showed EWSR1-CREB1 transcript in the case analyzed. CONCLUSION:
      We identified the presence of either EWSR1-CREB1 or EWSR1-ATF1 in all the cases,
      strengthening the concept of chromosomal promiscuity between AFH and clear cell
      sarcoma. Either the occurrence of a second unknown tumor-specific molecular event
      or, perhaps more likely, divergent differentiation programs of the putatively
      distinct precursor cells of AFH and clear cell sarcoma might be invoked in order
      to explain the two different phenotypes.

PMID- 18094414
TI  - HLA Tetramer Based Artificial Antigen-Presenting Cells Efficiently Stimulate CTLs
      Specific for Malignant Glioma.
AB  - PURPOSE: The interleukin-13 receptor alpha 2 (IL-13R alpha 2) is a glioma
      restricted cell-surface epitope not otherwise detected within the central nervous
      system. Here, we report a novel approach for targeting malignant glioma with IL
      13R alpha 2-specific CTLs. EXPERIMENTAL DESIGN: Artificial antigen-presenting
      cells (aAPC) were made by coating human leukocyte antigen (HLA)-A2/pIL-13R alpha
      2(345-354) tetrameric complexes, anti-CD28 antibody, and CD83 molecules to cell
      sized latex beads, and used to stimulate IL-13R alpha 2-specific CTLs from the
      peripheral blood mononuclear cells of HLA-A2+ healthy donors. After multiple
      stimulations, the induced CTLs were analyzed for tetramer staining, IFN-gamma
      production, and CTL reactivity. RESULTS: Tetramer staining assay showed that the
      induced CTLs specifically bound HLA-A2/pIL-13R alpha 2(345-354) tetramers. The
      CTLs specifically produced IFN-gamma in response to the HLA-A2/pIL-13R alpha
      2(345-354)-aAPCs and exhibited specific lysis against T2 cells pulsed with the
      peptide pIL-13R alpha 2(345-354) and HLA-A2+ glioma cells expressing IL-13R alpha
      2(345-354), whereas HLA-A2(-) glioma cell lines that express IL-13R alpha 2(345
      354) could not be recognized by the CTLs. The peptide-specific activity was
      inhibited by anti-HLA class I monoclonal antibody. CONCLUSION: The induced CTLs
      specific for IL-13R alpha 2(345-354) peptide could be a potential target of
      specific immunotherapy for HLA-A2+ patients with malignant glioma.

PMID- 18094415
TI  - Mitochondrial resequencing arrays detect tumor-specific mutations in salivary
      rinses of patients with head and neck cancer.
AB  - PURPOSE: Alterations of the mitochondrial genome have been identified in multiple
      solid tumors and in many head and neck squamous cell carcinomas (HNSCC).
      Identification of mitochondrial mutations in the salivary rinses of patients with
      HNSCC has potential application in disease detection. In this study, we used the
      MitoChip v2.0 mitochondrial genome resequencing array to detect minor populations
      of mitochondrial DNA in salivary rinses of patients with HNSCC. EXPERIMENTAL
      DESIGN: Salivary rinses from 13 patients with HNSCC, whose tumors carried
      mitochondrial mutations, were collected before surgical resection. DNA isolated
      from salivary rinses and serial dilutions of DNA derived from HNSCC-derived cell
      lines with known mitochondrial mutations were sequenced using the MitoChip, and
      analyzed using a quantitative algorithm which we developed to detect minor
      populations of mitochondrial DNA from MitoChip probe intensity data. RESULTS: We
      detected heteroplasmic populations of mitochondrial DNA up to a 1:200 dilution
      using MitoChip v2.0 and our analysis algorithm. A logarithmic relationship
      between the magnitude of assay intensity and concentration of minor mitochondrial
      populations was shown. This technique was able to identify tumor-specific
      mitochondrial mutations in salivary rinses from 10 of 13 (76.9%) patients with
      head and neck cancer. CONCLUSIONS: Minor populations of mitochondrial DNA and
      disease-specific mitochondrial mutations in salivary rinses of patients with
      HNSCC can be successfully identified using the MitoChip resequencing array and
      the algorithm which we have developed. This technique has potential application
      in the surveillance of patients after resection and may have applicability in the
      surveillance of body fluids in other tumor types.

PMID- 18094416
TI  - Gene expression-based molecular diagnostic system for malignant gliomas is
      superior to histological diagnosis.
AB  - PURPOSE: Current morphology-based glioma classification methods do not adequately
      reflect the complex biology of gliomas, thus limiting their prognostic ability.
      In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which
      typically follow distinct clinical courses. Our goal was to construct a
      clinically useful molecular diagnostic system based on gene expression profiling.
      EXPERIMENTAL DESIGN: The expression of 3,456 genes in 32 patients, 12 and 20 of
      whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma,
      respectively, was measured by PCR array. Next to unsupervised methods, we did
      supervised analysis using a weighted voting algorithm to construct a diagnostic
      system discriminating anaplastic oligodendroglioma from glioblastoma. The
      diagnostic accuracy of this system was evaluated by leave-one-out cross
      validation. The clinical utility was tested on a microarray-based data set of 50
      malignant gliomas from a previous study. RESULTS: Unsupervised analysis showed
      divergent global gene expression patterns between the two tumor classes. A
      supervised binary classification model showed 100% (95% confidence interval, 89.4
      100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic
      genes. Applied to a gene expression data set from a previous study, our model
      correlated better with outcome than histologic diagnosis, and also displayed
      96.6% (28 of 29) consistency with the molecular classification scheme used for
      these histologically controversial gliomas in the original article. Furthermore,
      we observed that histologically diagnosed glioblastoma samples that shared
      anaplastic oligodendroglioma molecular characteristics tended to be associated
      with longer survival. CONCLUSIONS: Our molecular diagnostic system showed
      reproducible clinical utility and prognostic ability superior to traditional
      histopathologic diagnosis for malignant glioma.

PMID- 18094417
TI  - BRCA1 mutation and young age predict fast breast cancer growth in the Dutch,
      United Kingdom, and Canadian magnetic resonance imaging screening trials.
AB  - PURPOSE: Magnetic resonance imaging (MRI) screening enables early detection of
      breast cancers in women with an inherited predisposition. Interval cancers
      occurred in women with a BRCA1 mutation, possibly due to fast tumor growth. We
      investigated the effect of a BRCA1 or BRCA2 mutation and age on the growth rate
      of breast cancers, as this may influence the optimal screening frequency.
      EXPERIMENTAL DESIGN: We reviewed the invasive cancers from the United Kingdom,
      Dutch, and Canadian MRI screening trials for women at hereditary risk, measuring
      tumor size at diagnosis and on preceding MRI and/or mammography. We could assess
      tumor volume doubling time (DT) in 100 cancers. RESULTS: Tumor DT was estimated
      for 43 women with a BRCA1 mutation, 16 women with a BRCA2 mutation, and 41 women
      at high risk without an identified mutation. Growth rate slowed continuously with
      increasing age (P = 0.004). Growth was twice as fast in BRCA1 (P = 0.003) or
      BRCA2 (P = 0.03) patients as in high-risk patients of the same age. The mean DT
      for women with BRCA1/2 mutations diagnosed at ages < or =40, 41 to 50, and >50
      years was 28, 68, and 81 days, respectively, and 83, 121, and 173 days,
      respectively, in the high-risk group. Pathologic tumor size decreased with
      increasing age (P = 0.001). Median size was 15 mm for patients ages < or =40
      years compared with 9 mm in older patients (P = 0.003); tumors were largest in
      young women with BRCA1 mutations. CONCLUSION: Tumors grow quickly in women with
      BRCA1 mutations and in young women. Age and risk group should be taken into
      account in screening protocols.

PMID- 18094418
TI  - Loss of heterozygosity at D8S298 is a predictor for long-term survival of
      patients with tumor-node-metastasis stage I of hepatocellular carcinoma.
AB  - PURPOSE: Our previous studies have shown that chromosome 8p deletion correlates
      with metastasis of hepatocellular carcinoma (HCC). This study was to determine
      whether 8p deletion could be used in predicting the prognosis of patients with
      HCC, particularly in those with early stage of HCC. EXPERIMENTAL DESIGN: A total
      of 131 patients with tumor-node-metastasis (TNM) stage I of HCC who underwent
      curative liver resection were enrolled. Loss of heterozygosity (LOH) was examined
      using 10 microsatellite markers at chromosome 8p, as well as 14 microsatellites
      at chromosome 1p, 17p, 4q, 13q, and 16q, and their association with 5-year
      overall survival (OS) and disease-free survival (DFS) of patients was analyzed.
      RESULTS: In the entire cohort of patients, the mean LOH frequency at these 24
      loci was 43.2%; LOH frequencies at D8S298 and D1S199 were 31.5% and 33.7%,
      respectively. LOH at D8S298 was associated with a worse 5-year OS (P = 0.008) and
      DFS (P = 0.038) in patients with TNM stage I of HCC. Likewise, the patients with
      LOH at D1S199 had a worse 5-year OS (P < 0.001) and DFS (P = 0.014) compared with
      those without LOH at D1S199. In multivariate analyses, LOH at D8S298 was an
      independent predictor of decreased DFS (hazard ratio, 0.372; 95% 95% confidence
      interval, 0.146-0.948; P = 0.038), whereas LOH at D1S199 was an independent
      predictor of decreased OS (hazard ratio, 0.281; 95% confidence interval, 0.123
      0.643; P = 0.003). CONCLUSIONS: LOH at D8S298 and D1S199 is independently
      associated with a worse survival in patients with TNM stage I of HCC after
      curative resection and could serve as novel prognostic predictors for this
      subgroup of patients.

PMID- 18094419
TI  - Proteomic profiling identifies afamin as a potential biomarker for ovarian
      cancer.
AB  - PURPOSE: To discover and validate serum glycoprotein biomarkers in ovarian cancer
      using proteomic-based approaches. EXPERIMENTAL DESIGN: Serum samples from a
      "discovery set" of 20 patients with ovarian cancer or benign ovarian cysts or
      healthy volunteers were compared by fluorescence two-dimensional differential in
      gel electrophoresis and parallel lectin-based two-dimensional profiling.
      Validation of a candidate biomarker was carried out with Western blotting and
      immunoassay (n = 424). RESULTS: Twenty-six proteins that changed significantly
      were identified by mass spectrometric sequencing. One of these, confirmed by
      Western blotting, was afamin, a vitamin E binding protein, with two isoforms
      decreasing in patients with ovarian cancer. Validation using cross-sectional
      samples from 303 individuals (healthy controls and patients with benign,
      borderline, or malignant ovarian conditions and other cancers) assayed by ELISA
      showed significantly decreased total afamin concentrations in patients with
      ovarian cancer compared with healthy controls (P = 0.002) and patients with
      benign disease (P = 0.046). However, the receiver operating characteristic areas
      for total afamin for the comparison of ovarian cancer with healthy controls or
      benign controls were only 0.67 and 0.60, respectively, with comparable figures
      for CA-125 being 0.92 and 0.88 although corresponding figures for a subgroup of
      samples analyzed by isoelectric focusing for afamin isoform 2 were 0.85 and 0.79.
      Analysis of a further 121 samples collected prospectively from 9 patients
      pretreatment through to relapse indicated complementarity of afamin with CA-125,
      including two cases in whom CA-125 was noninformative. CONCLUSIONS: Afamin shows
      potential complementarity with CA-125 in longitudinal monitoring of patients with
      ovarian cancer, justifying prospective larger-scale investigation. Changes in
      specific isoforms may provide further information.

PMID- 18094420
TI  - PAM4-reactive MUC1 is a biomarker for early pancreatic adenocarcinoma.
AB  - PURPOSE: The anti-MUC1 monoclonal antibody (MAb), PAM4, has a high specificity
      for pancreatic adenocarcinoma compared with other cancers, normal tissues, or
      pancreatitis. In order to assess its role in early pancreatic cancer development,
      we examined the expression of the PAM4-reactive MUC1 in the noninvasive precursor
      lesions, pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary
      mucinous neoplasia (IPMN). EXPERIMENTAL DESIGN: Tissue microarrays prepared from
      formalin-fixed, paraffin-embedded specimens were assessed by immunohistology for
      expression of the PAM4-reactive, non-variable number of tandem repeats (VNTR),
      MUC1 epitope, and the VNTR epitope bound by the MA5 MAb. RESULTS: The PAM4
      reactive MUC1 epitope was not detected in normal pancreas but was expressed in
      87% (48 of 55) of invasive pancreatic adenocarcinomas, including early stage 1
      disease: PAM4 labeled 94% (44 of 47) of the earliest PanIN lesions, PanIN-1A and
      1B, along with 91% (10 of 11) of PanIN-2, 40% (2 of 5) of PanIN-3, and 86% (31 of
      36) of intraductal papillary mucinous neoplasia lesions. A mostly diffuse pattern
      of labeling was observed. A second, unrelated, anti-MUC1 MAb, MA5, showed
      considerably less sensitivity with early PanIN-1 lesions; only 61% (25 of 41)
      were positive and the labeling did not differentiate normal pancreas from PanINs.
      CONCLUSIONS: The results suggest that expression of the PAM4-reactive antigen may
      represent an early event in the development of invasive pancreatic
      adenocarcinoma, and is unrelated to the VNTR peptide core epitopes of MUC1.
      Detection of this biomarker using immunohistology, in vitro immunoassays, and in
      vivo antibody-based imaging may provide new opportunities for the early detection
      and improved diagnosis of pancreatic cancer.

PMID- 18094421
TI  - Hypoxia-inducible factor 1 alpha in clear cell renal cell carcinoma.
AB  - PURPOSE: Hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays an important role
      in tumoral adaptation to hypoxic conditions by serving as a transcription factor
      for several crucial proteins, including vascular endothelial growth factor and
      carbonic anhydrase IX (CAIX). Here, we evaluated the significance of HIF-1 alpha
      in renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: Immunohistochemical analysis
      was done on a tissue microarray constructed from paraffin-embedded primary tumor
      specimens from 357 patients treated by nephrectomy for RCC. Nuclear expression
      was evaluated by a single pathologist who was blinded to outcome. The expression
      levels were associated with pathologic variables and survival. RESULTS: HIF-1
      alpha expression was greater in RCC than in benign tissue. Clear cell RCC showed
      the highest expression levels. In clear cell RCC, HIF-1 alpha was significantly
      correlated with markers of apoptosis (p21, p53), the mammalian target of
      rapamycin pathway (pAkt, p27), CXCR3, and proteins of the vascular endothelial
      growth factor family. HIF-1 alpha was correlated with CAIX and CAXII in
      localized, but not in metastatic RCC. HIF-1 alpha expression predicted outcome in
      metastatic patients: patients with high HIF-1 alpha expression (>35%) had
      significantly worse survival than patients with low expression (< or =35%);
      median survival, 13.5 versus 24.4 months, respectively (P = 0.005). Multivariate
      analysis retained HIF-1 alpha and CAIX expression as the strongest independent
      prognostic factors for patients with metastatic clear cell RCC. CONCLUSIONS: HIF
      1 alpha is an important independent prognostic factor for patients with
      metastatic clear cell RCC. Because HIF-1 alpha and CAIX are independently and
      differentially regulated in metastatic clear cell RCC, both tumor markers can be
      complementary in predicting prognosis.

PMID- 18094422
TI  - Influence of CYP3A4 inhibition on the steady-state pharmacokinetics of imatinib.
AB  - PURPOSE: To evaluate the effects of ritonavir, a potent inhibitor of CYP3A4, on
      the steady-state pharmacokinetics of imatinib. EXPERIMENTAL DESIGN: Imatinib
      pharmacokinetics were evaluated in cancer patients receiving the drug for at
      least 2 months, after which ritonavir (600 mg) was administered daily for 3 days.
      Samples were obtained on the day before ritonavir (day 1) and on the third day
      (day 4). The in vitro metabolism of imatinib with or without ritonavir and the
      effect of imatinib on 1-OH-midazolam formation rate, a probe for CYP3A4 activity,
      were evaluated with human CYP3A4 and pooled liver microsomes. RESULTS: In 11
      evaluable patients, the geometric mean (95% confidence interval) area under the
      curve of imatinib on days 1 and 4 were 42.6 (33.0-54.9) microg.h/mL and 41.2
      (32.1-53.1) microg.h/mL, respectively (P = 0.65). A population analysis done in
      NONMEM with a time-dependent covariate confirmed that ritonavir did not influence
      the clearance or bioavailability of imatinib. In vitro, imatinib was metabolized
      to the active metabolite CGP74588 by CYP3A4 and CYP3A5 and, to a lesser extent,
      by CYP2D6. Ritonavir (1 micromol/L) completely inhibited CYP3A4-mediated
      metabolism of imatinib to CGP74588 but inhibited metabolism in microsomes by only
      50%. Imatinib significantly inhibited CYP3A4 activity in vitro. CONCLUSION: At
      steady state, imatinib is insensitive to potent CYP3A4 inhibition and relies on
      alternate elimination pathways. For agents with complex elimination pathways that
      involve autoinhibition, interaction studies that are done after a single dose may
      not be applicable when drugs are administered chronically.

PMID- 18094423
TI  - Pharmacokinetic and tumor distribution characteristics of temsirolimus in
      patients with recurrent malignant glioma.
AB  - PURPOSE: To characterize the pharmacokinetics of temsirolimus and its major
      metabolite, sirolimus, in patients receiving enzyme-inducing antiepileptic drugs
      (EIAED) compared with patients receiving non-EIAEDs. An additional objective was
      to determine whether concentrations of temsirolimus or sirolimus were achieved in
      brain tumor tissue. EXPERIMENTAL DESIGN: Patients with recurrent malignant
      gliomas not receiving EIAEDs initially received temsirolimus weekly at a dose of
      250 mg i.v. The dose was subsequently reduced to 170 mg due to intolerable side
      effects. For patients taking EIAEDs, the starting dose of temsirolimus was 250 mg
      with standard dose escalation until the maximal tolerated dose was established.
      Ten whole blood samples were obtained over a period of 24 h after administration
      of temsirolimus for pharmacokinetic assessments. Patients eligible for
      cytoreductive surgery received temsirolimus before tumor resection. Whole blood
      and tumor tissue were obtained for analysis. RESULTS: Significant differences in
      the pharmacokinetic variables for temsirolimus and sirolimus were observed
      between the two patient groups at a comparable dose level of 250 mg. For patients
      receiving EIAEDs, the systemic exposure to temsirolimus was lower by 1.5-fold.
      Likewise, peak concentrations and exposure to sirolimus were lower by 2-fold.
      Measurable concentrations of temsirolimus and sirolimus were observed in brain
      tumor specimens. The average tissue to whole blood ratio for temsirolimus was
      1.43 and 0.84 for sirolimus. CONCLUSIONS: Drugs that induce cytochrome P450 3A4,
      such as EIAEDs, significantly affect the pharmacokinetics of temsirolimus and its
      active metabolite, sirolimus. Total exposure to temsirolimus and sirolimus was
      lower in the EIAED group at the maximum tolerated dose of 250 mg compared with
      the non-EIAED group at the maximum tolerated dose of 170 mg. However, brain tumor
      tissue concentrations of temsirolimus and sirolimus were relatively comparable in
      both groups of patients at their respective dose levels. Correlative analyses of
      the tissue for the inhibition of the key regulators (p70S6 kinase and 4E-binding
      protein 1) of mammalian target of rapamycin are necessary to define the
      therapeutic significance of the altered exposure to temsirolimus.

PMID- 18094424
TI  - L-arginine reduces cell proliferation and ornithine decarboxylase activity in
      patients with colorectal adenoma and adenocarcinoma.
AB  - PURPOSE: Evidence suggests that the majority of colorectal carcinomas arise from
      adenomas, and L-arginine suppresses colorectal tumorigenesis. We suppose that L
      arginine may inhibit the process of carcinogenesis from colorectal adenoma to
      adenocarcinoma. The aim of this study was to investigate the effects of L
      arginine on the formation and development of colorectal tumors. EXPERIMENTAL
      DESIGN: We selected 60 patients with colorectal cancer and 60 patients with
      colorectal adenoma (CRA) and divided them into four groups of 30 patients each.
      We gave 30 g (120 mL) of L-arginine everyday for 3 days to the test groups,
      whereas L-arginine was substituted by 5% glucose in the control groups. The
      expression of the proliferating cell nuclear antigen, survivin, and nitric oxide
      synthase was examined immunohistochemically, and ornithine decarboxylase (ODC)
      activity was examined spectrophotometrically. Serum nitric oxide (NO) was
      detected by the Griess assay. RESULTS: In patients with CRA, the proliferating
      cell nuclear antigen and survivin labeling indexes and ODC activity of the tumor
      and paratumor mucosa in the L-arginine-treated group after L-arginine treatment
      were significantly lower as compared with the corresponding pretreatment values
      (P < 0.01). Moreover, inducible nitric oxide synthase expression in the tumor
      markedly increased after L-arginine treatment (P < 0.05). Serum NO levels in the
      patients with colorectal cancer were markedly higher than those in the patients
      with CRA, and L-arginine treatment was responsible for this increase (P < 0.05).
      CONCLUSIONS: Our results show that L-arginine can restrain crypt cell
      hyperproliferation and the expression of survivin, an inhibitor of apoptosis
      protein. This suggests that L-arginine can block the formation and development of
      colorectal tumors, and this effect might be related to the increased serum NO
      concentration and decreased ODC activity.

PMID- 18094425
TI  - BRCA1 mRNA expression levels predict for overall survival in ovarian cancer after
      chemotherapy.
AB  - PURPOSE: We investigated whether BRCA1 mRNA expression levels may represent a
      biomarker of survival in sporadic epithelial ovarian cancer following
      chemotherapy treatment. EXPERIMENTAL DESIGN: The effect of loss of BRCA1
      expression on chemotherapy response in ovarian cancer was measured in vitro using
      dose inhibition assays and Annexin V flow cytometry. Univariate and multivariate
      analyses were done to evaluate the relationship between BRCA1 mRNA expression
      levels and survival after chemotherapy treatment in 70 fresh frozen ovarian
      tumors. RESULTS: We show that inhibition of endogenous BRCA1 expression in
      ovarian cancer cell lines results in increased sensitivity to platinum therapy
      and decreased sensitivity to antimicrotubule agents. In addition, we show that
      patients with low/intermediate levels of BRCA1 mRNA have a significantly improved
      overall survival following treatment with platinum-based chemotherapy in
      comparison with patients with high levels of BRCA1 mRNA (57.2 versus 18.2 months;
      P = 0.0017; hazard ratio, 2.9). Furthermore, overall median survival for higher
      BRCA1-expressing patients was found to increase following taxane-containing
      chemotherapy (23.0 versus 18.2 months; P = 0.12; hazard ratio, 0.53).
      CONCLUSIONS: We provide evidence to support a role for BRCA1 mRNA expression as a
      predictive marker of survival in sporadic epithelial ovarian cancer.

PMID- 18094426
TI  - Pharmacodynamic markers of perifosine efficacy.
AB  - PURPOSE: It is critical to develop methods to quantify the early pharmacodynamic
      effects of targeted therapeutics in vivo to make drug development more efficient
      and ensure biologically relevant dosing. Furthermore, an ability to identify
      patients likely to respond to targeted therapeutics would decrease the size,
      duration, and cost of clinical trials, resulting in more efficient translation to
      improved patient outcomes. Recent studies suggest that perifosine inhibits the
      phosphatidylinositol-3'-kinase (PI3K) pathway by preventing cell membrane
      recruitment of the AKT pleckstrin homology domain. EXPERIMENTAL DESIGN: A novel
      functional proteomics technology, reverse phase protein array, was used to
      establish and quantify pharmacodynamic markers of perifosine efficacy. RESULTS:
      Perifosine selectively prevents AKT recruitment to the membrane and blocks
      activation of downstream effectors. Perifosine inhibited breast, ovarian, and
      prostate cancer models. Growth inhibition was associated with apoptosis.
      Activation of AKT as a consequence of genomic aberrations predicted perifosine
      efficacy. In cell lines and xenografts, there was a highly statistically
      significant correlation between the degree of antitumor efficacy of different
      perifosine doses and quantified down-regulation of phosphorylation of AKT and of
      its downstream targets, particularly S6. CONCLUSIONS: Because of a strong
      correlation between proportional modulation of PI3K pathway biomarkers and
      quantified perifosine efficacy, it is likely that early measurement of such
      pharmacodynamic biomarkers with reverse phase protein array will optimize
      selection of responding patients and guide perifosine dosing. Furthermore, PI3K
      pathway activation status may allow baseline selection of patients most likely to
      respond to perifosine alone or in combination with other therapies.

PMID- 18094427
TI  - Tumors established with cell lines selected for oxaliplatin resistance respond to
      oxaliplatin if combined with cetuximab.
AB  - PURPOSE: To establish whether cetuximab, a chimeric IgG1 antibody targeting
      epidermal growth factor receptor, has the potential to restore responsiveness to
      oxaliplatin in preclinical cancer models, as has been shown with irinotecan in
      irinotecan refractory metastatic colorectal cancer patients. EXPERIMENTAL DESIGN:
      The effects of cetuximab and oxaliplatin, alone or in combination, were tested in
      vitro and in vivo using human colorectal cancer cell lines selected for
      oxaliplatin resistance, as well as parental control cell lines. Evaluations were
      made of subcutaneous xenograft tumor growth in nu/nu athymic mice, as well as
      activation of mitogen-activated protein kinase (extracellular signal-regulated
      kinase 1/2) and AKT, expression of DNA repair genes, density of
      apurinic/apyrimidinic DNA damage, and accumulation of platinum-DNA adducts in
      vitro. RESULTS: Oxaliplatin + cetuximab efficacy in murine subcutaneous xenograft
      models was greater than that of monotherapies and independent of the
      responsiveness to oxaliplatin monotherapy. In vitro, cetuximab reduced expression
      of excision repair cross-complementation group 1 and XPF, which are key
      components of the nucleotide excision repair pathway involved in the excision of
      platinum-DNA adducts. In addition, cetuximab reduced expression of XRCC1, a
      component of the base excision repair pathway responsible for the repair of
      apurinic/apyrimidinic sites. Effects of cetuximab on DNA repair protein levels
      were downstream to effects on mitogen-activated protein kinase and AKT pathway
      activation. In line with effects on DNA repair protein expression, cetuximab
      increased the accumulation of platinum and apurinic/apyrimidinic sites on DNA
      during oxaliplatin treatment. CONCLUSIONS: Cetuximab has the potential to salvage
      the benefits of oxaliplatin in oxaliplatin-resistant colorectal cancer patients
      by reducing DNA repair capacity.

PMID- 18094428
TI  - Modulation of reactive oxygen species in pancreatic cancer.
AB  - PURPOSE: The aim of the present study was to compare the effects of the three
      different forms of the antioxidant enzyme superoxide dismutase [i.e., manganese
      superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and
      extracellular superoxide dismutase (EcSOD)] on the malignant phenotype of human
      pancreatic cancer. EXPERIMENTAL DESIGN: Human pancreatic cancer cell lines were
      infected with adenoviral vectors containing the cDNAs for three different forms
      of the antioxidant enzyme SOD. Intratumoral injections of the adenoviral vectors
      were used in nude mice with human tumor xenografts. RESULTS: Increases in
      immunoreactive protein and enzymatic activity were seen after infections with the
      AdMnSOD, AdCuZnSOD, or AdEcSOD constructs. Increased SOD activity decreased
      superoxide levels and increased hydrogen peroxide levels. Increasing SOD levels
      correlated with increased doubling time. Cell growth and plating efficiency
      decreased with increasing amounts of the adenoviral constructs, with the
      AdCuZnSOD vector having the greatest effect in decreasing in vitro tumor growth.
      In contrast, inhibiting endogenous SOD with small interfering RNA increased
      superoxide levels and promoted tumor growth. Of the three SODs, tumors grew the
      slowest and survival was increased the greatest in nude mice injected with the
      AdEcSOD construct. CONCLUSIONS: Scavenging plasma membrane-generated superoxide
      may prove beneficial for suppression of pancreatic cancer growth.

PMID- 18094429
TI  - Differential effects of combined Ad5- delta 24RGD and radiation therapy in in
      vitro versus in vivo models of malignant glioma.
AB  - PURPOSE: The integrin-targeted conditionally replicating adenovirus Ad5-delta
      24RGD has been shown to possess strong oncolytic activity in experimental tumors
      and is currently being developed toward phase I clinical evaluation for ovarian
      cancer and malignant glioma. Previously, we reported that combination therapy of
      Ad5-delta 24RGD with irradiation led to synergistic antitumor activity in s.c.
      glioma xenografts. In the current study, the underlying mechanism of action to
      this synergy was studied and the effects of combined therapy were assessed in an
      orthotopic glioma model. EXPERIMENTAL DESIGN AND RESULTS: Sequencing studies in U
      87 monolayers showed that delivery of irradiation before Ad5-delta 24RGD
      infection led to a greater oncolytic effect than simultaneous delivery or
      infection before irradiation. This effect was not due to enhanced virus
      production or release. Experiments using a luciferase-encoding vector revealed a
      small increase in transgene expression in irradiated cells. In tumor spheroids,
      combination therapy was more effective than Ad5-delta 24RGD or irradiation alone.
      Staining of spheroid sections showed improved penetration of virus to the core of
      irradiated spheroids. Mice bearing intracranial tumors received a combination of
      Ad5-delta 24RGD with 1 x 5 Gy total body irradiation or with 2 x 6 Gy whole brain
      irradiation. In contrast to the in vitro data and reported results in s.c.
      tumors, addition of radiotherapy did not significantly enhance the antitumor
      effect of Ad5-delta 24RGD. CONCLUSIONS: Combined treatment with Ad5-delta 24RGD
      and irradiation shows enhanced antitumor activity in vitro and in s.c. tumors,
      but not in an orthotopic glioma model. These differential results underscore the
      significance of the selected tumor model in assessing the effects of combination
      therapies with oncolytic adenoviruses.

PMID- 18094430
TI  - NKG2D-mediated antitumor activity by tumor-infiltrating lymphocytes and antigen
      specific T-cell clones isolated from melanoma patients.
AB  - PURPOSE: The role of NKG2D receptor in antitumor immunosurveillance has not been
      completely clarified. We addressed this issue by investigating the involvement of
      this receptor in tumor-specific immunologic response in melanoma patients.
      EXPERIMENTAL DESIGN: We determined the presence of NKG2D+ T cells among tumor
      infiltrating lymphocytes (TIL) of 10 (one primary and 9 metastatic) melanoma
      samples and the expression of NKG2D ligands (NKG2DL) by these tumor cells.
      Moreover, the expression of NKG2D was assessed in a panel of antigen-specific T
      lymphocytes isolated from melanoma patients and the engagement of NKG2D in
      antitumor activity mediated by these T cells was determined. RESULTS: TILs
      located either in the periphery or within the tumor mass of melanoma samples
      expressed NKG2D and the expression of this receptor by T cells was retained after
      in vitro culture. However, NKG2DLs were weakly expressed, or not expressed, by
      most metastatic lesions with only the primary tumor being positive for all these
      molecules. In contrast, these ligands were expressed, although heterogeneously,
      by all in vitro established melanoma lines. Moreover, the engagement of NKG2D
      occurred in antitumor activity by both freshly isolated and in vitro cultured
      TILs. However, this receptor was involved to a different extent in the antitumor
      activity of antigen-specific T-cell clones. CONCLUSIONS: These findings indicate
      that NKG2D+ T cells have a role in the immunologic response against tumor. Thus,
      new immunotherapeutic treatments for melanoma patients should be designed aimed
      at augmenting the NKG2D+ T lymphocyte-mediated immune response.

PMID- 18094431
TI  - Allogeneic MHC gene transfer enhances an effective antitumor immunity in the
      early period of autologous hematopoietic stem cell transplantation.
AB  - PURPOSE: In autologous hematopoietic stem cell transplantation (HSCT),
      lymphopenia-induced homeostatic proliferation of T cells is driven by the
      recognition of self-antigens, and there is an opportunity to skew the T-cell
      repertoire during the T-cell recovery by engaging tumor-associated antigens,
      leading to a break of tolerance against tumors. However, the homeostatic
      proliferation-driven antitumor responses seem to decline rapidly in association
      with tumor growth. We hypothesized that a tumor-specific immune response induced
      by an immune gene therapy could enhance and sustain homeostatic proliferation
      induced antitumor immunity. EXPERIMENTAL DESIGN: The antitumor effect of
      allogeneic MHC (alloMHC) gene transfer was examined at the early phase of the
      immune reconstitution after syngeneic HSCT. RESULTS: Syngeneic HSCT showed
      significant tumor growth inhibition of syngeneic colon cancer cells within a
      period of 30 days; however, the tumor then resumed rapid growth and the survival
      of the mice was not prolonged. In contrast, when the alloMHC plasmid was
      intratumorally injected at the early phase after syngeneic HSCT, the established
      tumors were markedly regressed and the survival of recipient mice was prolonged
      without significant toxicities, whereas no survival advantage was recognized in
      recipient mice injected with a control plasmid. This tumor suppression was
      evident even in the other tumors that were not injected with the alloMHC plasmid.
      The antitumor response was characterized by the development of tumor-specific T
      cell- and natural killer cell-mediated cytotoxicities. CONCLUSION: The results
      suggest the efficacy and safety of integrating intratumoral alloMHC gene transfer
      with an autologous HSCT for the treatment of solid cancers.

PMID- 18094432
TI  - Evidence for microtubule target engagement in tumors of patients receiving
      ixabepilone.
AB  - PURPOSE: Microtubule-stabilizing agents, such as taxanes, have been shown to be
      effective anticancer drugs. alpha-Tubulin, a basic unit of microtubules, can
      undergo several posttranslational modifications after assembly into stabilized
      microtubules, including acetylation and detyrosination. These modifications have
      been observed in cell cultures after exposure to microtubule stabilizers. Our
      objective was to develop a straightforward and dependable assay to show tubulin
      target engagement in tumor tissue after treatment of patients with
      ixabepilone(BMS-247550; Ixempra). EXPERIMENTAL DESIGN: Levels of
      posttranslationally modified alpha-tubulin were assessed in lysates of cultured
      malignant cell lines, as well as in both tumor tissue and peripheral blood
      mononuclear cells derived from patients before and after treatment with
      ixabepilone. Modification-specific antibodies permitted quantitative Western blot
      analysis. RESULTS: In cultured cell lines, the levels of detyrosinated (glu
      terminated) and acetylated alpha-tubulin increased after microtubule
      stabilization induced by ixabepilone. ixabepilone treatment also induced a 2-fold
      to 25-fold increase in detyrosinated alpha-tubulin levels in 11 of 13 serial
      biopsies and a 2-fold to 100-fold increase in acetylated alpha-tubulin in 11 of
      12 serial biopsies obtained from patients receiving ixabepilone. Overall, little
      or no difference in tubulin modifications were observed between the before and
      after ixabepilone treatment in lysates from their peripheral blood mononuclear
      cells at the time point examined. CONCLUSION: Assessing the levels of
      detyrosinated and/or acetylated alpha-tubulin seems to provide a simple and
      reliable assay to show target engagement by the microtubule-stabilizing agent
      ixabepilone. Such analyses may provide further understanding of therapeutic
      success or failure of microtubule-stabilizing agents in cancer therapy.

PMID- 18094434
TI  - Fractionated versus standard continuous light delivery in interstitial
      photodynamic therapy of dunning prostate carcinomas.
AB  - PURPOSE: The study aims to compare the standard/continuous light delivery with
      fractionated light delivery for interstitial photodynamic therapy (PDT) of
      prostate cancer. EXPERIMENTAL DESIGN: Dunning R3327 prostate tumor models were
      established in male syngeneic rats. When tumors reached approximately 3,000 mm3,
      animals were randomized to various treatment groups. Three hours after QLT0074
      injection, tumors were illuminated by 690-nm light delivered by a computer
      controlled switch, which sequentially directed light to one of the seven optical
      fibers in cycles. For comparison, tumors were treated with continuous
      illumination. Tumors treated with light-only served as control. Dynamic contrast
      enhanced magnetic resonance imaging was used to monitor tumor perfusion changes
      before and after PDT. RESULTS: Tumor response (animal survival) to PDT with
      fractionated light delivery was PDT dose dependent in both tumor models. Rats
      bearing anaplastic tumor treated by fractionated light (PDT dose: 1.5 mg/kg
      QLT0074, 900 J light) had a median survival of 51 days with 25% tumor cures
      compared with that of 26 days with no tumor cure by continuous illumination (P =
      0.015) and 14 days by light-only (P = 0.0001). Rats bearing well-differentiated
      tumor treated by fractionated light had a median survival of 82 days compared
      with 65 days by continuous illumination (P = 0.001) and 37 days by light-only.
      PDT with fractionated light generated a perfusion reduction of 80% compared with
      52% for continuous illumination in well-differentiated tumors. CONCLUSIONS:
      Fractionated light delivery is more effective than continuous light delivery in
      PDT of prostate cancer (solid tumors). These results warrant further
      investigation in clinical trials.

PMID- 18094433
TI  - Clinical and biological significance of vascular endothelial growth factor in
      endometrial cancer.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is critical for angiogenesis
      and tumor progression; however, its role in endometrial cancer is not fully
      known. Therefore, we examined the clinical and therapeutic significance of VEGF
      in endometrial carcinoma using patient samples and an endometrioid orthotopic
      mouse model. EXPERIMENTAL DESIGN: Following Institutional Review Board approval,
      VEGF expression and microvessel density (MVD) counts were evaluated using
      immunohistochemistry in 111 invasive endometrioid endometrial cancers by two
      independent investigators. Results were correlated with clinicopathologic
      characteristics. For the animal model, Ishikawa or Hec-1A cancer cell lines were
      injected directly into the uterine horn. Therapy experiments with bevacizumab
      alone or in combination with docetaxel were done and samples were analyzed for
      markers of angiogenesis and proliferation. RESULTS: Of 111 endometrial cancers,
      high expression of VEGF was seen in 56% of tumors. There was a strong correlation
      between VEGF expression and MVD (P < 0.001). On multivariate analysis, stage (P =
      0.04), grade (P = 0.003), VEGF levels (P = 0.03), and MVD (P = 0.037) were
      independent predictors of shorter disease-specific survival. In the murine model,
      whereas docetaxel and bevacizumab alone resulted in 61% to 77% tumor growth
      inhibition over controls, combination therapy had the greatest efficacy (85-97%
      inhibition over controls; P < 0.01) in both models. In treated tumors,
      combination therapy significantly reduced MVD counts (50-70% reduction over
      controls; P < 0.01) and percent proliferation (39% reduction over controls; P <
      0.001). CONCLUSIONS: Increased levels of VEGF and angiogenic markers are
      associated with poor outcome in endometrioid endometrial cancer patients. Using a
      novel orthotopic model of endometrioid endometrial cancer, we showed that
      combination of antivascular therapy with docetaxel is highly efficacious and
      should be considered for future clinical trials.

PMID- 18094435
TI  - A novel polymorphism in the promoter region of ERBB4 is associated with breast
      and colorectal cancer risk.
AB  - PURPOSE: The receptor tyrosine kinase ERBB4/HER4 plays a role in cell division,
      migration, differentiation, as well as apoptosis, and is frequently overexpressed
      in breast and colorectal tumors. To understand the role of genetic variations in
      the regulation of ERBB4 expression, we identified new polymorphisms and
      investigated their functional implication and risk association with breast and
      colorectal cancer. EXPERIMENTAL DESIGN: We screened colorectal tumors from 92
      patients for genetic variants at the ERBB4 ATG -1000 bp 5'-regulatory region by
      denaturing high-performance liquid chromatography and sequencing. Variants were
      subjected to DNA-protein interaction analyses (electrophoretic mobility shift
      assay), reporter gene assays in breast cancer cell lines MDA134 and MDA157, and
      immunohistochemical analyses of breast tumors. We established genotype
      frequencies within a breast cancer case-control collection (1,021 cases, 1,015
      population-based controls) and a colorectal cancer case-control collection (459
      cases, 569 blood donors) using matrix-assisted laser desorption ionization/time
      of flight mass spectrometry. Adjusted odds ratios (OR) and 95% confidence
      intervals (CI) were assessed by multivariate logistic regression. RESULTS: We
      identified five new germ line variants -815 A>T, -782 G>T, -638 insTC, -267 C>G,
      and -219 del10bp. Two variants showed in vitro functional effects. The -782T
      allele showed lower protein binding affinity and lower promoter activity compared
      with the -782G allele, however, the -815T allele showed higher protein binding
      affinity and higher promoter activity. The -782T variant was identified as a risk
      allele for breast and colorectal cancer (OR, 1.59; 95% CI, 1.06-2.34 and OR,
      2.21; 95% CI, 1.22-3.99, respectively). CONCLUSION: The ERBB4 -782 G>T
      polymorphism, by virtue of its in vitro functional implication and incidence, is
      a risk factor for breast and colorectal cancer.

PMID- 18094436
TI  - Analysis of hMLH1 missense mutations in East Asian patients with suspected
      hereditary nonpolyposis colorectal cancer.
AB  - PURPOSE: Germ line mutations in the DNA mismatch repair gene hMLH1 are a frequent
      cause of hereditary nonpolyposis colorectal cancer and about one-third of these
      are missense mutations. Several missense mutations in hMLH1 have frequently been
      detected in East Asian patients with suspected hereditary nonpolyposis colorectal
      cancer, but their pathogenic role has not been extensively assessed. The aim of
      this study was to perform functional analyses of these variants and their
      association with gastrointestinal cancer in East Asians. EXPERIMENTAL DESIGN:
      Altogether, 10 hMLH1 variants were analyzed by yeast two-hybrid and
      coimmunoprecipitation assays. RESULTS: The carboxyl-terminal replacements Q542L,
      L549P, L574P, and P581L in hMLH1 resulted in complete loss of activity in both
      yeast two-hybrid and coimmunoprecipitation tests and thus might be considered as
      pathogenic. The amino-terminal variants S46I, G65D, G67R, and R217C did not
      affect complex formation with hPMS2 in coimmunoprecipitation, but partly or fully
      lost their activity in yeast two-hybrid assay, and we suggested that these
      variants might reduce the efficiency of the heterodimer to go into the nucleus
      and thus the mismatch repair function might be blocked or reduced. The V384D and
      the Q701K variant resulted in the interaction of hMLH1 with hPMS2 at reduced
      efficiency and might raise the gastrointestinal cancer risk of the mutation
      carriers. CONCLUSIONS: This work availably evaluated the functional consequences
      of some missense mutations not previously determined in the hMLH1 gene and might
      be useful for the clinical diagnosis of hereditary gastrointestinal cancer,
      especially in East Asians.

PMID- 18094438
TI  - [11C]docetaxel and positron emission tomography for noninvasive measurements of
      docetaxel kinetics.

PMID- 18094439
TI  - The immunoregulatory function of indoleamine 2, 3 dioxygenase and its application
      in allotransplantation.
AB  - Indolemine 2, 3-dioxygenase (IDO) is a cytosolic monomeric hemoprotein enzyme
      that catalyses tryptophan, the least available essential amino acid in the human
      body, to N-formylkynurenine, which in turn rapidly degrades to give kynurenine.
      IDO is expressed in different tissues, especially and prominently in some subsets
      of antigen presenting cells (APCs) of lymphoid organs and also in the placenta of
      human and other mammals. Expression of IDO by certain dendritic cells, monocytes
      and macrophages has a regulatory effect on T cells probably by providing a
      tryptophan-deficient microenvironment and/or accumulation of toxic metabolites of
      tryptophan. This immunomodulatory function of IDO plays an essential role in
      different physiological and pathological states. IDO was shown to prevent
      rejection of the fetus during pregnancy, possibly by inhibiting alloreactive T
      cells. Moreover, IDO expression in APCs was suggested to control autoreactive
      immune responses. In this review we discuss the molecular and biological
      characteristics of IDO and its function in immune system as well as the potential
      application of this enzyme in improving the outcome of allogeneic transplantation
      as a local immunosuppressive factor.

PMID- 18094440
TI  - Alteration of peripheral blood T-reg cells and cytokines production in
      angiography personnel exposed to scattered X-rays.
AB  - Angiocardiography is an X-ray examination of the blood vessels or chambers of the
      heart. Cardiologists and staff members applying this procedure are exposed to
      high levels of scattered radiation. In our previous study the incidence of
      unstable chromosomal aberrations and cytokinesis-blocked micronuclei were found
      to be significantly higher in exposed individuals than the age and sex matched
      controls. In the present study we assessed cytokine production by peripheral
      blood mononuclear cells of the above cases and the percentage of Treg cells.
      According to film dosimeter analysis, personnels received 0.25-15 mSv during the
      previous year (average of 3 mSv/y). Isolated PBMCs from the test and control
      groups were stimulated with Phorbol Myristate Acetate/ Ionomycin (PMA/I).
      Cytokine production was measured in the supernatants of cultured lymphocytes. The
      percentage of Treg cells was studied by flow cytometry. The production of IL-10
      and IL-5 was significantly down-regulated in the test group compared to the
      control group. In contrast, IL-12 was up-regulated. Yet, no statistically
      significant difference was found for IFN- gamma between two groups. In addition,
      we found higher percentage of CD4+CD25+(bright) Treg cells in the study group
      compared to the controls. Taken together, it was shown that low doses of
      scattered X-rays could skew cytokine profile of peripheral blood mononuclear
      cells in favour of inflammatory response causing the increase of Treg cells.

PMID- 18094441
TI  - Specific IgG antibodies (total and subclasses) against Saffron pollen: a study of
      their correlation with specific IgE and immediate skin reactions.
AB  - Saffron (Zaaferan), botanical name Crocus sativus, is the most expensive spice in
      the world. It is derived from the dried stigma and pistil of the purple saffron
      crocus flowers. Iran is the largest saffron producer accounting for more than 80%
      of the world's production. Saffron contains an aeroallergen that causes reactive
      respiratory allergic reactions in atopic subjects. IgG antibody to allergens in
      the serum of allergic patients is not routinely measured. In this study in order
      to find out more about mechanism of allergy against saffron pollen, specific
      antibodies (IgE and IgG, total and subclasses) in atopic subjects were assayed.
      We used an ELISA assay for measuring specific IgE and IgG against saffron pollen
      extract in the sera of 38 atopic subjects (test group) and 20 non allergic
      subjects (control group). The optical densities were compared between allergic
      subjects and non-allergic individuals. The prick test with saffron pollen extract
      was used to evaluate the cutaneous and specific antibody responses in the
      allergic subjects. The correlation was determined by statistical analysis.
      Specific saffron pollen IgE and IgG subclasses were found significantly higher in
      the allergic subjects than the control group. The immediate skin reaction was
      found positive in 70% of the test group. We report here, the existence of a
      positive correlation between specific IgE and skin reaction by prick test in
      atopic subjects (R= 0.433). A negative correlation between specific IgE and IgG4
      subclass was also found (R= -0.576). These data may be useful to understand the
      mechanism of allergy to saffron and may help in clarifying clinical
      manifestations and to prevent IgE production as well as therapeutic application.

PMID- 18094442
TI  - Relationship of IgG avidity index and IgM levels for the differential diagnosis
      of primary from recurrent cytomegalovirus infections.
AB  - Since the incidence of symptomatic congenital cytomegalovirus infection is low
      (~0.05%) and risk factors are not well defined, it is difficult to develop
      strategies for prevention. The aim of this study was to recognise the utility of
      specific Immunoglobulin G avidity analysis for distinguishing primary infection
      from past/recurrent infection. Sera from 50 women with cytomegalovirus specific
      Immunoglobulin M antibodies without proven seroconversion and infants born to
      these women were tested for presence of Immunoglobulin M antibodies by commercial
      enzyme immunoassay. For cytomegalovirus specific immunoglobulin G avidity, sera
      were measured by commercial kit according to manufacturer's recommendations.
      Among 50 sera form mothers, 26 showed the presence of Immunoglobulin M antibodies
      out of which 15 had low avidity antibodies. Out of 50 sera from children, 18
      showed the presence of Immunoglobulin M antibodies. Out of these 18 sera from
      children, 12 were symptomatic, which all showed the presence of low avidity
      antibodies. The results showed that an avidity index <40% and presence of
      Immunoglobulin M antibodies is highly suggestive of a recent primary infection.

PMID- 18094443
TI  - Systemic and local reactions of bee venom immunotherapy in Iran.
AB  - Severe allergic reactions during specific immunotherapy may occur in the
      treatment of hymenoptera sting allergy. The objective of the present study was to
      examine the characteristics of allergic reactions during specific immunotherapy
      in patients with allergy towards hymenoptera venom in the Iranian population. A
      prospective study was performed using the clinical reports of 27 patients with
      anaphylaxis to bee venom (Apis melifera, Geupes vespula and Geupes Polites). Ten
      patients treated with Cluster protocol during 2002 and 2006 After diagnosis of
      hymenoptera sting allergy according to history and intradermal tests, the patient
      were treated with Cluster protocol immunotherapy. The protocol lasted 6 weeks
      with an increase in the concentration of venom from 0.01 microg/ml to 100
      microg/ml. None of the patient received premedication. All patients with
      hymenoptera venom allergy received 120 injections. Anaphylactic reactions were
      classified according to the Mueller-classification. The frequencies of systemic
      reactions during Cluster protocol were 8.33% and 5% for yellow jacket and honey
      bee venom respectively. No patient experienced severe systemic reaction. Cluster
      protocol for hymenoptera immunotherapy is a reliable method for the treatment of
      anaphylactic reactions to bee venom. It is safe with low cost and do not need
      hospitalization.

PMID- 18094444
TI  - Clinical differentiation between resistant asthma and chronic bronchiolitis:
      testing a practical approach.
AB  - Intractable asthma is a challenging clinical problem. This study was conducted to
      determine whether a subset of patients with Intractable asthma may be
      misdiagnosed and have a form of bronchiolitis instead and also to determine the
      effectiveness of macrolide therapy in these patients. Seventy six patients with
      Intractable asthma were re-treated with recommended maximal doses of oral
      prednisolone for 5 days, beclomethasone, cromolyn sodium, salbutamol and
      ipratropium bromide for 30 days. Thirty five patients were considered as
      unresponsive and constituted the study group. They underwent high-resolution CT
      (HRCT) scan following which they were offered with video-assisted thoracoscopic
      surgical biopsy. Group 1 (n= 27) refused biopsy and each was treated with
      macrolide therapy, while Group 2 (n=8) underwent biopsy, and then received
      macrolide therapy. The patients were treated and followed for three months. The
      study group consisted of 27 patients, with a mean age of 46.9 +/- 11.1 years. The
      mean duration of time between the onset of symptoms and the start of this study
      was 8.1 years. In group 2, no patient had pathologic findings of asthma, and 7/8
      had a form of bronchiolitis. There was significant improvement in dyspnea, cough
      and pulmonary function indices at the end of the 3-month in both groups (p<
      0.001). Our results suggest that patients with Intractable asthma could be
      misdiagnosed and some of them have some forms of chronic bronchiolitis. We
      believe that any patient who does not respond to standard treatments for
      Intractable asthma should be evaluated with expiratory HRCT; those with
      significant air trapping should be considered for a course of macrolide therapy
      or biopsy for better identification of the underlying disease.

PMID- 18094445
TI  - Prevalence of asthma and rhinitis in bakery workers in the city of Sanandaj,
      Iran.
AB  - Baker's asthma is one of the most common forms of occupational asthma. This study
      was conducted to determine prevalence of asthma and rhinitis among bakery workers
      in the city of Sanandaj, the provincial center of Kurdistan province in the west
      of Iran in the in Summer 2006. In this study 776 bread bakery workers were
      included. These subjects were selected randomly among 1620 bakery workers. The
      diagnosis of asthma was based on a medical history of episodic symptoms of cough,
      chest tightness, and dyspnea and spirometry. Airflow obstruction was determined
      with spirometry, the definition of airflow obstruction which was used in this
      study was an FEV1/FVC ratio < 0.8, and FEV1 or FVC increases of > or = 12 percent
      and at least 200 mL after using a short-acting inhaled beta2-agonist. Rhinitis
      was diagnosed by typical history of work related symptoms. Analyses were
      performed on 776 subjects (all were men) without missing data for asthma and
      rhinitis. All of subjects were male with mean age of 33.69+/-11.09 years. Mean
      duration of bakery working for these subjects was 13.91+/-9.37 years. Prevalence
      of asthma at the time of study was 11.9%. 93 subjects were diagnosed as asthma
      with history, physical and spirometry findings. 31 (33.3%) of asthmatic workers
      were diagnosed as asthma previously and 62 (66.6%) workers were known as new
      asthmatic patients which were diagnosed in this study program. The prevalence of
      rhinitis was (9.9%). Subjects with asthma had longer history of working at bakery
      than others (P=0.001). Asthma prevalence among these bakery workers that were
      included in our study was similar and in some instances the prevalence was lower
      than other studies.

PMID- 18094446
TI  - Lymphocytic bronchiolitis as presenting disorder in an undiagnosed adult patient
      with chronic granulomatous disease.
AB  - Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency disease.
      Although the most affected patients are diagnosed in childhood, there are several
      reports of the disease presenting in adult patients. Here we present a 40 years
      old man who was admitted in hospital due to respiratory symptoms and ground glass
      pattern in high resolution computed tomography of lung. Open lung biopsy revealed
      lymphocytic bronchiolitis. Because of past medical history of granulomatous
      lesion in lung and recurrent abscesses of skin and soft tissue, NBT test was
      conducted which its result revealed that the disorder was compatible with CGD and
      then it was confirmed by fluorescent cytometry.

PMID- 18094447
TI  - Human leukocyte antigen profile of two ethnic groups in Southeast of Iran.
AB  - This study was performed to determine the genetic diversity of HLA class I and II
      alleles among two ethnic groups in Southeastern Iran. HLA profiles were
      determined in 71 Iranian populations (41 Zaboli and 30 Baloch). The frequencies
      of HLA-A02 (p=0.017), -Cw4 (p=0.003), and -DR8 (p=0.025) in the Zaboli
      populations were significantly higher than that in Baloch ethnic group. In
      contrast, the frequency of HLA-A23 allele was more frequent in Baloch than Zaboli
      (p=0.020). This report represents an important resource for investigators in the
      fields of transplantation immunology and population genetics from widely
      dispersed areas of Iran.

PMID- 18094448
TI  - Mechanotransduction in leukocyte activation: a review.
AB  - We review recent evidence which suggests that leukocytes in the circulation and
      in the tissue may readily respond to physiological levels of fluid shear stress
      in the range between about 1 and 10 dyn/cm 2, a range that is below the level to
      achieve a significant passive, viscoelastic response. The response of activated
      neutrophilic leukocytes to fluid shear consists of a rapid retraction of
      lamellipodia with membrane detachment from integrin binding sites. In contrast, a
      subgroup of non-activated neutrophils may project pseudopods after exposure to
      fluid shear stress. The evidence suggests that G-protein coupled receptor
      downregulation by fluid shear with concomitant downregulation of Rac-related
      small GTPases and depolymerization of F-actin serves to retract the lamellipodia
      in conjunction with proteolytic cleavage of beta 2 integrin to facilitate
      membrane detachment. Furthermore, there exists a mechanism to up- and down
      regulate the fluid shear-response, which involves nitric oxide and the second
      messenger cyclic guanosine monophosphate (cGMP). Many physiological activities of
      circulating leukocytes are under the influence of fluid shear stress, including
      transendothelial migration of lymphocytes. We describe a disease model with
      chronic hypertension that suffers from an attenuated fluid shear-response with
      far reaching implications for microvascular blood flow.

PMID- 18094449
TI  - A fractional derivative model to describe arterial viscoelasticity.
AB  - Arterial viscoelasticity can be described with a complex modulus (E*) in the
      frequency domain. In arteries, E* presents a power-law response with a plateau
      for higher frequencies. Constitutive models based on a combination of purely
      elastic and viscous elements can be represented with integer order differential
      equations but show several limitations. Recently, fractional derivative models
      with fewer parameters have proven to be efficient in describing rheological
      tissues. A new element, called "spring-pot", that interpolates between springs
      and dashpots is incorporated. Starting with a Voigt model, we proposed two
      fractional alternative models with one and two spring-pots. The three models were
      tested in an anesthetized sheep in a control state and during smooth muscle
      activation. A least squares method was used to fit E*. Local activation induced a
      vascular constriction with no pressure changes. The E* results confirmed the
      steep increase from static to dynamic values and a plateau in the range 2-30 Hz,
      coherent with fractional model predictions. Activation increased E*, affecting
      its real and imaginary parts separately. Only the model with two spring-pots
      correctly followed this behavior with the best performance in terms of least
      squares errors. In a context where activation separately modifies E*, this
      alternative model should be considered in describing arterial viscoelasticity in
      vivo.

PMID- 18094450
TI  - Flow behaviour of a POSS biopolymer solution.
AB  - A non-biodegradable polyhedral oligomeric silsesquioxane (POSS) nanocomposite
      biopolymer has been developed for fabrication of medical devices and for tissue
      engineering human organs. The polymer in solution, containing 2 wt% of POSS, has
      been synthesized, characterized and investigated to determine its key rheological
      properties. Thus, the variation of shear stress and viscosity as a function of
      shear rate has been determined at ambient temperature to estimate yield stress
      and the index of pseudoplasticity, respectively. The temperature dependence of
      viscosity and the effect of ageing on the viscosity of the polymer have also been
      investigated. Results are compared with those of a conventional polycarbonate
      urethane (PCU) polymer solution. The POSS-PCU polymer solution shows near
      Newtonian behaviour in the shear rate range to 1000 s(-1), having an apparent
      viscosity of approximately 3000 mPa s and a pseudoplasticity index of 0.90,
      decreasing slightly as the polymer solution is aged over 9 months. The
      temperature dependence of viscosity of the POSS polymer is extremely low and does
      not change with ageing but the yield strength increases from 2.7 Pa to 8.3 Pa.

PMID- 18094451
TI  - Development of a flow-through system to create occluding thrombus.
AB  - Occlusive thrombosis accounts for many heart attacks and strokes. These acute
      events are difficult to catch in patients and animal test methods may be
      misleading because anti-thrombotic therapeutics often do not cross-react with
      different species. This paper presents a new flow-through system that leads to
      rapid occlusive thrombosis in arterial flow conditions. Whole porcine blood is
      perfused through a tubular test section. The growing thrombus is visualized in
      real time from early platelet attachment, through accumulation, to occlusion. The
      progression of flow rate reduction provides a clear distinguishing parameter
      between thrombus formation and embolization. Thrombus growth rate is a linear
      function of very high shear rate beyond 40,000 s(-1). The histology of the
      thrombus reveals predominantly platelet accumulation and growth as a rough
      surface with tendrils. This flow-through system may be useful for the economic
      testing of new anti-thrombosis therapies.

PMID- 18094452
TI  - Optical analysis of red blood cell sediment formation.
AB  - The red blood cell (RBC) sediment formation was studied using an optical method.
      The intensity of light transmitted through the blood sample was measured as a
      function of time and distance from the bottom of the sample. Blood was obtained
      from healthy donors and measurements were performed at initial hematocrits
      ranging from 30 to 50%. Sedimentation curves and time dependence of the intensity
      averaged along the height of the RBC suspension were determined to give a
      cumulative description of the process. Detailed analysis of the transmitted light
      intensity revealed a moving interface between sedimenting RBC aggregates and the
      forming of a deposit of the cells. It was shown that although there is no
      discontinuity in the intensity an averaged interface can be found. A novel curve
      describing the sedimentation process called the deposit formation curve was
      found. Below this curve a formation of the RBC deposit occurs. Firstly, this
      curve represents the position of the interface between sedimenting RBC aggregates
      and a forming deposit, secondly this curve coincides with the last part of the
      sedimentation curve.

PMID- 18094453
TI  - The effect of radiographic contrast media on the morphology of human
      erythrocytes.
AB  - Echinocyte formation is associated with a rigidification of the cells that
      possibly affects capillary diffusion and, consequently, the tissue's oxygen
      supply. This study examines how many echinocytes appeared after the addition of
      various concentrations of radiographic contrast media (RCM) (Iodixanol 320,
      Iohexol 350, Iopromide 370, Iomeprol 350 and Iomeprol 400 mg Iodine/ml) compared
      to red blood cells in isotonic saline solution as well as in autologous plasma.
      Isotonic saline solution, Iodixanol, Iohexol, Iomeprol 350, Iomeprol 400 and
      Iopromide in concentrations of 10%, 20% or 40% were added to the plasma of six
      healthy subjects. Subsequently, the erythrocytes were resuspended in these
      RCM/plasma mixtures, incubated for 5 minutes at 37 degrees C and then examined
      under the microscope.The various mixtures and concentrations of the RCM in the
      mixture all had a significant effect on the number of discocytes (p<0.0001). The
      percentage of discocytes for all concentrations significantly depended on the
      RCM/plasma mixture (p=0.0097). Of all the RCM/plasma mixtures used as well as of
      the NaCl/plasma mixtures, the Iodixanol/plasma mixture showed the most similar
      discocyte fraction compared to red blood cells in the autologous plasma. At the
      same time, while Iodixanol in this respect differed from all other RCMs, the
      other RCMs only differed little from one another with respect to the discocyte
      fraction.

PMID- 18094454
TI  - Effects of strenuous exercise on blood coagulation activity in sickle cell trait
      carriers.
AB  - We compared routine coagulation markers in six sickle cell trait carriers ((SCT,
      or AS hemoglobinopathy)--the heterozygous form of sickle cell anemia) and six
      subjects with normal hemoglobin before and after a prolonged and intense
      exercise. Blood was sampled at rest and at the end of the entire exercise test to
      measure coagulation markers (prothrombin time, activated partial thromboplastin
      time, plasma fibrinogen and antithrombin III activity), hematocrit (Hct) and
      yield stress (tau(y)). Results obtained at the end of exercise were corrected by
      the percent change in plasma volume. Blood coagulation markers, Hct and tau(y)
      were not different between the two groups at rest. Exercise did not change
      prothrombin time, antithrombin III activity and plasma fibrinogen, decreased
      activated partial thromboplastin time and increased Hct and tau(y) in the two
      groups. These parameters were not significantly different between the two groups
      at the end of exercise, except for plasma fibrinogen which was slightly higher in
      SCT carriers but in the normal range values. The results have been discussed in
      relation with some cases of exercise-related sudden death in SCT carriers,
      reported in several studies. Therefore our results show that the increased risk
      for clinical complications in certain SCT carriers during exercise seems to be
      unrelated to higher blood coagulation activity.

PMID- 18094455
TI  - Haemorheological changes in patients with systemic lupus erythematosus do not
      seem to be related to thrombotic events.
AB  - Atherothrombotic events are significant factors of mortality and morbidity in
      patients with systemic lupus erythematosus (SLE). The extent that rheological
      factors may be involved in these events in these patients has not been
      established. We measured the following rheological parameters in 86 patients with
      SLE, of whom 16 had suffered venous and/or arterial thrombotic events, and in 86
      healthy controls: fibrinogen (Fbg), plasma viscosity (PV), blood viscosity at 230
      s(-1) both at native haematocrit (BVn 230 s(-1) and corrected to 45% (BVc 230 s(
      1), erythrocyte aggregation at stasis (AE0) and at 3 s(-1) (AE1), aggregation
      time (Ta), aggregation index at 10 s (AI10), disaggregation threshold (gammaD),
      and erythrocyte deformability (ED). In addition glucose, total cholesterol (T
      Chol), triglycerides (TG), haematocrit (Hct) and Body Mass Index (BMI) were
      determined. SLE Disease Activity Index (SLEDAI) was also assessed. The patients
      showed a significant increase in BMI (P=0.030), TG (P<0.001), PV (P=0.007), AE0
      (P=0.005), AE1 (P=0.006), AI10 (P=0.024), gammaD (P=0.001), Fbg (P=0.050); and a
      significant decrease in Ta (P<0.001), Hct (P<0.001) and BVn 230 s(-1) (P=0.003).
      When patients with SLEDAI<or>10 were compared, the latter had lower Hct (P=0.041)
      and lower BVn 230 s(-1) (P=0.017) than those with less SLEDAI. No significant
      differences were found in any of the parameters analysed on comparing patients
      who had suffered a thrombotic event with those who had not. Our results suggest
      that, although patients with SLE have moderate rheological changes, these do not
      seem to be responsible for the increase in the thrombotic tendency in these
      patients.

PMID- 18094456
TI  - Contrast harmonic ultrasound and indocyanine-green fluorescence video angiography
      for evaluation of dermal and subdermal microcirculation in free parascapular
      flaps.
AB  - PURPOSE: Contrast harmonic ultrasound (CHI) with a linear transducer is a new
      diagnostic approach that allows dynamic and quantitative flow detection of tissue
      perfusion in microsurgery. The aim of the study was the evaluation of perfusion
      of the dermal and subdermal layers of microvascular tissue transplants with CHI
      in comparison to ICG-fluorescence angiography. MATERIAL AND METHOD: In a
      prospective clinical study indocyanine-green fluorescence video angiography and
      contrast enhanced high resolution ultrasound (5-10 MHz; linear transducer; Logiq
      9; GE) were used for evaluation of the microcirculation in 10 transplanted free
      parascapular flaps. Two regions were analysed, the centre of the flap and the
      region of the anastomosis. The perfusion patterns of both methods were compared.
      RESULTS: The perfusion indexes measured by ICG-fluorescence angiography
      correlated very precisely in all patients with the quantitative perfusion curves
      of contrast-enhanced US with CHI. Two flaps with slow filling and low dye
      intensity showed low contrast enhancement in CHI with modified perfusion curves
      with slow increase. In two cases a reduced perfusion and filling were found.
      There were no statistical differences between the two diagnostic methods
      (p>0.01). CONCLUSION: CHI improves US detections of dermal and subdermal
      microcirculation in comparison to ICG fluorescence angiography. CHI is a new
      diagnostic method for postoperative monitoring of free flaps.

PMID- 18094457
TI  - Platelet aggregation under high shear conditions during and after a 28-day
      administration of 100 mg acetylsalicylic acid in healthy volunteers.
AB  - Platelet primary hemostatic function occurs under high shear conditions.
      Cyclooxygenase inhibitors such as ibuprofen inhibit this platelet aggregation
      under high shear rates only to a limited extent. This prompted the present study
      on 10 healthy volunteers treated with 100 mg aspirin for 4 weeks. The platelet
      function analyser (PFA-100) was used to measure the closure time (CT) of a
      membrane pore coated with collagen and epinephrine by aggregating platelets under
      shear rates of 5000-6000 s(-1). A first dose of 100 mg aspirin prolonged the CT
      above the normal range in 4 of 10 individuals, but the CT for the whole group
      (153+/-42 s) was not different from baseline (112+/-18 s). After 7 and 28 days of
      treatment, CTs were >300 s in 8 individuals and the mean values for the group
      were significantly higher than baseline. However, one subject had an intermediate
      response and one had an aspirin non-responsiveness, which was not overcome by 300
      mg aspirin daily. The CT was normalized in 4 individuals 48 h after the last
      aspirin dose and in 7 individuals after 72 h, when the mean value for the group
      became not different from baseline. We conclude that the platelet function
      measured with the PFA-100 is not inhibited significantly after a single dose of
      100 mg aspirin, is thereafter inhibited consistently in the majority, but not all
      individuals during a 4 week treatment, and returns to normal in 48-72 h. Since
      large interindividual differences exist, monitoring of platelet inhibition at the
      beginning of an aspirin treatment should be considered and validated in a
      prospective study.

PMID- 18094458
TI  - Low hematocrit per blood viscosity ratio as a mortality risk factor in coronary
      heart disease.
AB  - Increased blood viscosity has not been associated with mortality risk in coronary
      heart disease (CHD). We aimed to investigate the predictive power of hematocrit
      per blood viscosity (Hct/BV) ratio as a marker of rheological oxygen carrying
      capacity of the blood to assess mortality risk of CHD. Elective coronary
      angiography was performed and CHD was proved in 109 patients in 1996 and 1997. In
      78 cases (72%) complete follow up information was obtained in February 2006.
      During the follow up time (mean 8.9 years) 10 patients died due to cardiac cause
      (group C). Two patients died due to non-cardiac cause and 66 were still alive at
      the end of the follow up period (group NC, n=68). Mean hematocrit per blood
      viscosity (Hct/BV) ratio was significantly lower in group C comparing to NC (87+/
      5; 93+/-9 Pa(-1)s(-1), SD, respectively, p=0.022). Other factors (body mass
      index, serum cholesterol, fibrinogen, hematocrit, plasma and blood viscosity,
      cardiac index, left ventricular ejection fraction) provided no statistical
      differences. Kaplan-Meier survival analysis showed only the impact of fibrinogen
      and Hct/BV ratio on cardiac mortality (p=0.029 and 0.009, respectively). Receiver
      operating characteristic curves proved only Hct/BV ratio to be able to
      differentiate between groups (area under curve: 0.716, p=0.028). Hct/BV ratio
      showed significant negative correlation with the frequency of hospital admissions
      (r=-0.377, p=0.03). Low Hct/BV ratio can be regarded as a risk factor of cardiac
      death in CHD.

PMID- 18094460
TI  - Increased hematocrit and reduced blood pressure following control of glycemia in
      diabetes.
AB  - In this study we determine the effects of reducing blood glucose on mean arterial
      blood pressure (MAP) and hematocrit (Hct) in patients with type 2 diabetes who
      are not responding to conventional treatment in an intensive treatment program 1
      year after initiation of treatment. Data on MAP, glucose and Hct was obtained
      from 21 diabetic type 2 individuals subjected to personalized treatment and
      compared (paired statistics) to pretreatment conditions. Exclusion criteria were
      severe retinopathy, diabetic nephropathy, amputation of diabetic foot and
      increased glucose>50 mg/dl. Treatment was the combined administration of
      glibenclamide and metformin dosed to obtain a reduction of glucose levels.
      Exercise and strict adherence to a prescribed diet were prescribed in all cases.
      One year after initiation of therapy, glucose decreased from 219 +/- 87 to 158+/
      51 mg/dl (p<0.002), Hct increased from 41.6 +/- 3.2 to 44.7+/-2.9% (p<0.001) and
      MAP decreased from 100.6 +/- 11.0 to 94.3+/-7.2 mmHg (p<0.001). There were no
      statically significant changes in cholesterol and triglyceride concentrations.
      The patients lost weight (72.5+/-12.6 to 70.3+/-13.0 kg, p<0.001) and lowered
      blood creatinine concentration from 1.04+/-0.24 to 0.95+/-0.25 mg/dl, p<0.05. The
      increase in Hct should correspond to an increase in blood viscosity of about 12%,
      however blood pressure, and presumably vascular resistance, decreased by 6%. It
      is proposed that these effects are in part related to improved kidney function
      resulting in increased Hct and blood viscosity which increases vascular wall
      shear stress and NO bioavailability leading to a vasodilator effect.

PMID- 18094461
TI  - An introduction to molecular replacement.
AB  - Molecular replacement is fundamentally a simple trial-and-error method of solving
      crystal structures when a suitable related model is available. The underlying
      simplicity of the method is often obscured by the mathematical trickery required
      to make the searches computationally tractable. This introduction sketches the
      essential issues in molecular replacement without going into technical details.
      General search strategies are discussed and the alternative Patterson and
      likelihood approaches are outlined.

PMID- 18094462
TI  - AMoRe: classical and modern.
AB  - An account is given of the latest developments of the AMoRe package: new
      rotational search algorithms, exploitation of noncrystallographic symmetry,
      generation and use of ensemble models and interactive graphical molecular
      replacement.

PMID- 18094463
TI  - The befores and afters of molecular replacement.
AB  - This review addresses the essential questions to consider when attempting to
      phase a new crystal structure using molecular replacement. Sequence matching can
      suggest whether there is a suitable three-dimensional model available, but it is
      also important to analyse the model in order to find its likely oligomeric state
      and to establish whether there are likely to be domain movements. Once a solution
      has been found it must be refined, which can be challenging for low-homology
      models. There is a detailed discussion of structures used as examples for CCP4
      tutorials.

PMID- 18094464
TI  - Sequence alignment for molecular replacement.
AB  - This article focuses on the key step of obtaining the best possible sequence
      alignment of the Query (the protein you are interested in) to the Target (a
      protein of known three-dimensional structure) in order to build a molecular model
      for molecular replacement. Common sequence-alignment methods are discussed,
      starting from structural alignment and then moving to pairwise, multiple and
      profile-profile methods. The limitations of sequence-alignment methods and
      guidelines on how to judge the likely accuracy of alignment are considered. This
      is not a detailed tutorial on how to use specific programs; rather, the reader is
      directed to current tools and techniques that are likely to yield good results.

PMID- 18094465
TI  - Model preparation in MOLREP and examples of model improvement using X-ray data.
AB  - The success of molecular replacement is critically dependent on the quality of
      the search model. Several model-preparation procedures are integrated in the
      molecular-replacement program MOLREP. These include model modification on the
      basis of amino-acid sequence alignment and model correction based on analysis of
      the solvent-accessibility of the atoms. The packing function used in MOLREP for
      the translational search is explained in the context of model preparation. In
      difficult cases, bioinformatics-based modifications are not sufficient for
      successful molecular replacement. An approach implemented in MOLREP for solving
      cases with translational noncrystallographic symmetry is an example of model
      preparation in which analysis of X-ray data plays an essential role. In addition,
      two examples are presented in which the X-ray data were used to refine partial
      models for subsequent use in molecular replacement.

PMID- 18094466
TI  - Dealing with structural variability in molecular replacement and crystallographic
      refinement through normal-mode analysis.
AB  - Normal-mode analysis (NMA) can be used to generate multiple structural variants
      of a given template model, thereby increasing the chance of finding the molecular
      replacement solution. Here, it is shown that it is also possible to directly
      refine the amplitudes of the normal modes against experimental data (X-ray or
      cryo-EM), generalizing rigid-body refinement methods by adding just a few
      additional degrees of freedom that sample collective and large-amplitude
      movements. It is also argued that the situation where several (conformations of)
      models are present simultaneously in the crystal can be studied with adjustable
      occupancies using techniques derived from statistical thermodynamics and already
      used in molecular modelling.

PMID- 18094467
TI  - ARP/wARP and molecular replacement: the next generation.
AB  - Automatic iterative model (re-)building, as implemented in ARP/wARP and its new
      control system flex-wARP, is particularly well suited to follow structure
      solution by molecular replacement. More than 100 molecular-replacement solutions
      automatically solved by the BALBES software were submitted to three standard
      protocols in flex-wARP and the results were compared with final models from the
      PDB. Standard metrics were gathered in a systematic way and enabled the drawing
      of statistical conclusions on the advantages of each protocol. Based on this
      analysis, an empirical estimator was proposed that predicts how good the final
      model produced by flex-wARP is likely to be based on the experimental data and
      the quality of the molecular-replacement solution. To introduce the differences
      between the three flex-wARP protocols (keeping the complete search model,
      converting it to atomic coordinates but ignoring atom identities or using the
      electron-density map calculated from the molecular-replacement solution), two
      examples are also discussed in detail, focusing on the evolution of the models
      during iterative rebuilding. This highlights the diversity of paths that the flex
      wARP control system can employ to reach a nearly complete and accurate model
      while actually starting from the same initial information.

PMID- 18094468
TI  - Iterative model building, structure refinement and density modification with the
      PHENIX AutoBuild wizard.
AB  - The PHENIX AutoBuild wizard is a highly automated tool for iterative model
      building, structure refinement and density modification using RESOLVE model
      building, RESOLVE statistical density modification and phenix.refine structure
      refinement. Recent advances in the AutoBuild wizard and phenix.refine include
      automated detection and application of NCS from models as they are built,
      extensive model-completion algorithms and automated solvent-molecule picking.
      Model-completion algorithms in the AutoBuild wizard include loop building,
      crossovers between chains in different models of a structure and side-chain
      optimization. The AutoBuild wizard has been applied to a set of 48 structures at
      resolutions ranging from 1.1 to 3.2 A, resulting in a mean R factor of 0.24 and a
      mean free R factor of 0.29. The R factor of the final model is dependent on the
      quality of the starting electron density and is relatively independent of
      resolution.

PMID- 18094469
TI  - Combining X-ray and electron-microscopy data to solve crystal structures.
AB  - Low-resolution electron-microscopy reconstructions can be used as search models
      in molecular replacement or may be combined with existing monomeric structures in
      order to produce multimeric models suitable for molecular replacement. The
      technique is described in the case of viral and subviral particles as well as in
      the case of oligomeric proteins.

PMID- 18094470
TI  - From electron microscopy to X-ray crystallography: molecular-replacement case
      studies.
AB  - Multi-component molecular complexes are increasingly being tackled by structural
      biology, bringing X-ray crystallography into the purview of electron-microscopy
      (EM) studies. X-ray crystallography can utilize a low-resolution EM map for
      structure determination followed by phase extension to high resolution. Test
      studies have been conducted on five crystal structures of large molecular
      assemblies, in which EM maps are used as models for structure solution by
      molecular replacement (MR) using various standard MR packages such as AMoRe,
      MOLREP and Phaser. The results demonstrate that EM maps are viable models for
      molecular replacement. Possible difficulties in data analysis, such as the
      effects of the EM magnification error, and the effect of MR positional/rotational
      errors on phase extension are discussed.

PMID- 18094471
TI  - Fitting molecular fragments into electron density.
AB  - Molecular replacement is a powerful tool for the location of large models using
      structure-factor magnitudes alone. When phase information is available, it
      becomes possible to locate smaller fragments of the structure ranging in size
      from a few atoms to a single domain. The calculation is demanding, requiring a
      six-dimensional rotation and translation search. A number of approaches have been
      developed to this problem and a selection of these are reviewed in this paper.
      The application of one of these techniques to the problem of automated model
      building is explored in more detail, with particular reference to the problem of
      sequencing a protein main-chain trace.

PMID- 18094472
TI  - NCS-constrained exhaustive search using oligomeric models.
AB  - The efficiency of the cross-rotation function step of molecular replacement (MR)
      is intrinsically limited as it uses only a fraction of the Patterson vectors.
      Along with general techniques extending the boundaries of the method, there are
      approaches that utilize specific features of a given structure. In special cases,
      where the directions of noncrystallographic symmetry axes can be unambiguously
      derived from the self-rotation function and the structure of the homologue
      protein is available in a related oligomeric state, the cross-rotation function
      step of MR can be omitted. In such cases, a small number of yet unknown
      parameters defining the orientation of the oligomer and/or its internal
      organization can be optimized using an exhaustive search. Three difficult MR
      cases are reported in which these parameters were determined and the oligomer was
      positioned according to the maximal value of the correlation coefficient in a
      series of translation searches.

PMID- 18094473
TI  - Surprises and pitfalls arising from (pseudo)symmetry.
AB  - It is not uncommon for protein crystals to crystallize with more than a single
      molecule per asymmetric unit. When more than a single molecule is present in the
      asymmetric unit, various pathological situations such as twinning, modulated
      crystals and pseudo translational or rotational symmetry can arise. The presence
      of pseudosymmetry can lead to uncertainties about the correct space group,
      especially in the presence of twinning. The background to certain common
      pathologies is presented and a new notation for space groups in unusual settings
      is introduced. The main concepts are illustrated with several examples from the
      literature and the Protein Data Bank.

PMID- 18094474
TI  - Type II dehydroquinase: molecular replacement with many copies.
AB  - Type II dehydroquinase is a small (150-amino-acid) protein which in solution
      packs together to form a dodecamer with 23 cubic symmetry. In crystals of this
      protein the symmetry of the biological unit can be coincident with the
      crystallographic symmetry, giving rise to cubic crystal forms with a single
      monomer in the asymmetric unit. In crystals where this is not the case, multiple
      copies of the monomer are present, giving rise to significant and often confusing
      noncrystallographic symmetry in low-symmetry crystal systems. These different
      crystal forms pose a variety of challenges for solution by molecular replacement.
      Three examples of structure solutions, including a highly unusual triclinic
      crystal form with 16 dodecamers (192 monomers) in the unit cell, are described.
      Four commonly used molecular-replacement packages are assessed against two of
      these examples, one of high symmetry and the other of low symmetry; this study
      highlights how program performance can vary significantly depending on the given
      problem. In addition, the final refined structure of the 16-dodecamer triclinic
      crystal form is analysed and shown not to be a superlattice structure, but rather
      an F-centred cubic crystal with frustrated crystallographic symmetry.

PMID- 18094475
TI  - MrBUMP: an automated pipeline for molecular replacement.
AB  - A novel automation pipeline for macromolecular structure solution by molecular
      replacement is described. There is a special emphasis on the discovery and
      preparation of a large number of search models, all of which can be passed to the
      core molecular-replacement programs. For routine molecular-replacement problems,
      the pipeline automates what a crystallographer might do and its value is simply
      one of convenience. For more difficult cases, the pipeline aims to discover the
      particular template structure and model edits required to produce a viable search
      model and may succeed in finding an efficacious combination that would be missed
      otherwise. An overview of MrBUMP is given and some recent additions to its
      functionality are highlighted.

PMID- 18094476
TI  - BALBES: a molecular-replacement pipeline.
AB  - The number of macromolecular structures solved and deposited in the Protein Data
      Bank (PDB) is higher than 40 000. Using this information in macromolecular
      crystallography (MX) should in principle increase the efficiency of MX structure
      solution. This paper describes a molecular-replacement pipeline, BALBES, that
      makes extensive use of this repository. It uses a reorganized database taken from
      the PDB with multimeric as well as domain organization. A system manager written
      in Python controls the workflow of the process. Testing the current version of
      the pipeline using entries from the PDB has shown that this approach has huge
      potential and that around 75% of structures can be solved automatically without
      user intervention.

PMID- 18094477
TI  - The JCSG MR pipeline: optimized alignments, multiple models and parallel
      searches.
AB  - The success rate of molecular replacement (MR) falls considerably when search
      models share less than 35% sequence identity with their templates, but can be
      improved significantly by using fold-recognition methods combined with exhaustive
      MR searches. Models based on alignments calculated with fold-recognition
      algorithms are more accurate than models based on conventional alignment methods
      such as FASTA or BLAST, which are still widely used for MR. In addition, by
      designing MR pipelines that integrate phasing and automated refinement and allow
      parallel processing of such calculations, one can effectively increase the
      success rate of MR. Here, updated results from the JCSG MR pipeline are
      presented, which to date has solved 33 MR structures with less than 35% sequence
      identity to the closest homologue of known structure. By using difficult MR
      problems as examples, it is demonstrated that successful MR phasing is possible
      even in cases where the similarity between the model and the template can only be
      detected with fold-recognition algorithms. In the first step, several search
      models are built based on all homologues found in the PDB by fold-recognition
      algorithms. The models resulting from this process are used in parallel MR
      searches with different combinations of input parameters of the MR phasing
      algorithm. The putative solutions are subjected to rigid-body and restrained
      crystallographic refinement and ranked based on the final values of free R
      factor, figure of merit and deviations from ideal geometry. Finally, crystal
      packing and electron-density maps are checked to identify the correct solution.
      If this procedure does not yield a solution with interpretable electron-density
      maps, then even more alternative models are prepared. The structurally variable
      regions of a protein family are identified based on alignments of sequences and
      known structures from that family and appropriate trimmings of the models are
      proposed. All combinations of these trimmings are applied to the search models
      and the resulting set of models is used in the MR pipeline. It is estimated that
      with the improvements in model building and exhaustive parallel searches with
      existing phasing algorithms, MR can be successful for more than 50% of
      recognizable homologues of known structures below the threshold of 35% sequence
      identity. This implies that about one-third of the proteins in a typical
      bacterial proteome are potential MR targets.

PMID- 18094478
TI  - The 37th International Sun Valley Workshop on Skeletal Tissue Biology. Foreward.

PMID- 18094479
TI  - Primary cilia.

PMID- 18094480
TI  - The primary cilium: what once did nothing, now does everything.

PMID- 18094481
TI  - Shaping up and shipping out: the role of cilia in growth and patterning.

PMID- 18094482
TI  - Primary cilia in bone.

PMID- 18094483
TI  - Intraflagellar transport in skeletal development.

PMID- 18094484
TI  - The role of IGF system in the rise and fall in bone density with age.

PMID- 18094485
TI  - Dentin matrix protein 1 (DMP1).

PMID- 18094486
TI  - DMP1--a key regulator in mineralized matrix formation.

PMID- 18094487
TI  - Use of the transgenic approach to determine the role of DMP1 in phosphate
      regulation.

PMID- 18094488
TI  - The role of DMP1 in autosomal recessive hypophosphatemic rickets.

PMID- 18094489
TI  - DMP1 and MEPE expression are elevated in osteocytes after mechanical loading in
      vivo: theoretical role in controlling mineral quality in the perilacunar matrix.

PMID- 18094490
TI  - Heritability of lumbar trabecular bone mechanical properties in baboons.

PMID- 18094491
TI  - A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis.

PMID- 18094492
TI  - Pericyte/myofibroblast phenotype of osteoprogenitor cell.

PMID- 18094493
TI  - Ror2, a novel modulator of osteogenesis.

PMID- 18094494
TI  - A chemical and engineering approach towards "smart" synthetic bone grafts.

PMID- 18094495
TI  - ATF4 is a key molecule linking food intake and skeletal development.

PMID- 18094496
TI  - Bone tissue engineering.

PMID- 18094497
TI  - Gene therapy strategies for craniofacial tissue engineering.

PMID- 18094498
TI  - Biointerfaces promoting tissue healing.

PMID- 18094499
TI  - Biologic augmentation of polymer scaffolds for bone repair.

PMID- 18094500
TI  - Extracellular matrix elasticity directs stem cell differentiation.

PMID- 18094501
TI  - Designer biomaterials: too much information?

PMID- 18094502
TI  - Aging.

PMID- 18094503
TI  - The biology of aging.

PMID- 18094504
TI  - Aging and fragility of bone.

PMID- 18094505
TI  - Aging and sarcopenia.

PMID- 18094506
TI  - Vascular calcification.

PMID- 18094507
TI  - Aging and falls: causes and prevention.

PMID- 18094508
TI  - Osteonecrosis and osteonecrosis of the jaw (ONJ).

PMID- 18094509
TI  - Introduction to osteonecrosis of the femoral head (OFH) and osteonecrosis of the
      jaw (ONJ).

PMID- 18094510
TI  - Summary of ASBMR Task Force on ONJ.

PMID- 18094511
TI  - Distinguishing features of the oral cavity and its predisposition to
      osteonecrosis.

PMID- 18094512
TI  - Animal models of osteonecrosis of the jaw.

PMID- 18094513
TI  - Proceedings of the 37th Meeting of the International Sun Valley Workshop on
      Skeletal Tissue Biology. August 5-8, 2007. Sun Valley, Idaho, USA.

PMID- 18094515
TI  - Continuous infusion of PGE2 is catabolic with a negative bone balance on both
      cancellous and cortical bone in rats.
AB  - It is well documented that intermittent PGE(2) treatment increases both
      trabecular and cortical bone mass. However, the effects of continuous PGE(2)
      administration remain undocumented. The aim of the study was to investigate the
      effects of continuous prostaglandin E(2) (PGE(2)) on different bone sites in
      skeletally mature rats. Six-month-old Sprague Dawley rats were treated with
      PGE(2) at 1 or 3 mg/kg/d continuously via infusion pump for 21 days. Two other
      groups of rats received PGE(2) at the same doses by intermittent (daily)
      subcutaneous injections and served as positive controls. Histomorphometry was
      performed on cancellous bone of the proximal tibial metaphysis and cortical bone
      of the tibial shaft. As expected, intermittent PGE(2) treatment increased both
      cancellous and cortical bone mass by stimulating bone formation at the
      cancellous, periosteal and endocortical bone surfaces. In contrast, continuous
      PGE(2) treatment decreased cancellous bone mass with bone resorption exceeding
      bone formation. In addition, continuous PGE(2) treatment increased endocortical
      and intracortical bone remodeling, inducing bone loss which was partially offset
      by stimulating periosteal expansion. We conclude that continuous PGE(2) treatment
      induces overall catabolic effects on both cancellous and cortical bone envelopes,
      which differs from intermittent PGE(2) treatment that is anabolic. Lastly, we
      speculate that superior bone mass may be achieved by co-treatment of continuous
      PGE(2) in combination with an anti-catabolic agent.

PMID- 18094516
TI  - Association of lipoprotein-associated phospholipase A2 with coronary
      calcification among American and Japanese men.
AB  - BACKGROUND: We have previously reported that the prevalence of coronary artery
      calcification (CAC) was substantially lower among Japanese than American men
      despite a less favorable profile of many traditional risk factors in Japanese
      men. To determine whether lipoprotein-associated phospholipase A2 (Lp-PLA2)
      levels are related to the difference in the prevalence of CAC between the two
      populations. METHODS: A total of 200 men aged 40-49 years were examined: 100
      residents in Allegheny County, Pennsylvania, United States, and 100 residents in
      Kusatsu City, Shiga, Japan. Coronary calcium score (CCS) was evaluated by
      electron-beam tomography, Lp-PLA2 levels, nuclear magnetic resonance (NMR)
      lipoprotein subclasses, and other factors were assessed in 2001-2002. RESULTS: Lp
      PLA2 levels were higher among American than Japanese men (Mean +/- standard
      deviation 301.7 +/- 82.6 versus 275.9 +/- 104.7 ng/mL, respectively, p=0.06).
      Among all Japanese men and those with low density lipoprotein (LDL) cholesterol >
      or =130 mg/dL, there was an inverse association of the prevalence of CCS>0 with
      the tertile groups of Lp-PLA2 levels (p=0.08 and p=0.03, respectively). American
      men did not have any association between CCS>0 with the tertile groups of Lp-PLA2
      (p=0.62). Although Lp-PLA2 among both populations correlated positively with LDL
      and total cholesterol, American and Japanese men had different correlations with
      NMR lipoprotein subclasses. Reported high odds ratio for CCS>0 among American
      compared to Japanese men was not reduced after adjusting for Lp-PLA2 levels.
      CONCLUSION: Lp-PLA2 may have different mechanisms of action among American and
      Japanese men. Lp-PLA2 levels can not explain the observed CAC differences between
      the two populations.

PMID- 18094517
TI  - A community-based study of the willingness to pay associated with screening for
      diabetic retinopathy among type 2 diabetes in Kinmen, Taiwan.
AB  - BACKGROUND: In Taiwan, there were few population-based studies of WTP values
      related to DR screening among persons with type 2 diabetes. This community-based
      study was to explore the willingness- to-pay (WTP) values for screening for
      diabetic retinopathy (DR) associated with varying degrees of DR among persons
      with type 2 diabetes in Kinmen, Taiwan. METHODS: A total of 725 eligible
      community-dwelling adults diagnosed with type 2 diabetes received DR screening
      during 1999-2002 and then evaluated WTP values in 2003. Diagnosis of DR was
      performed by a panel of ophthalmologists using ophthalmoscopy and a 45-degree
      color retinal photographs to examine fundus after dilating pupils. WTP values
      were measured by discrete-choice method. RESULTS: The 406 adults with type 2
      diabetes participating in the WTP survey had a 56% response rate. Of 406
      subjects, 265 (65.3%) said they would be willing to pay for DR screening to
      reduce blindness. The overall mean WTP value was New Taiwan Dollars 468.9 +/-
      327.7 (US dollars 14.3 +/- 10.0). Age was borderline significant (p=0.07) related
      to WTP values. Those with severe stage DR had higher WTP values for screening
      than subjects with mild stage. CONCLUSIONS: Degree of DR was the independent
      factor affecting WTP values in DR screening among community-dwelling adults with
      type 2 diabetes.

PMID- 18094518
TI  - Risk and protective factors related to mortality from pneumonia among middleaged
      and elderly community residents: the JACC Study.
AB  - BACKGROUND: There have been few systematic investigations into risk and
      protective factors for pneumonia related mortality for community residents. This
      study investigated these factors utilizing a large cohort study on Japanese
      community residents. METHODS: Subjects, 110,792 individuals (aged 40-79 years)
      enrolled in 1988-1990, were followed until death, or when they moved away from
      the surveyed communities, or the end of 2003. Pneumonia death was defined
      following 480-486 (International Classification of Diseases, 9th Revision) or J12
      J18 (10th Revision). Age-adjusted and multivariate hazard ratios were calculated
      along with 95% confidence intervals using the Cox proportional hazards model.
      RESULTS: With 1,112,747 person-years of the study, a total of 1,246 persons died
      of pneumonia. We found history of blood transfusion (multivariate hazard
      ratio=2.0 [95% confidence interval: 1.7-2.4]) was a potent novel risk factor.
      Walking 0.5-1 hour/day (0.8 [0.6-1.0]), 1+ hour/day (0.7 [0.6-0.8]), and/or a
      history of pregnancy (0.6 [0.4-0.9]) were found to reduce pneumonia mortality. A
      large body mass index (BMI) (25+kg/m(2)) was a protective factor (0.7 [0.5-0.8]),
      while low BMI (<18) was confirmed as a risk one (2.1 [1.7-2.6]). Smoking was an
      important preventable risk factor (1.6 [1.3-1.9], population attributable risk
      proportion=14%), and its cessation reduced risk (0.7 [0.5-1.0]) to levels
      comparable to neversmokers (0.7 [0.5-1.0]). CONCLUSIONS: The risk and protective
      factors ascertained here for pneumonia mortality among community residents,
      history of blood transfusion, large BMI, and walking habits, warrant further
      study. Smoking cessation may effectively reduce pneumonia mortality.

PMID- 18094519
TI  - Metabolic syndrome mortality in a population-based cohort study: Jichi Medical
      School (JMS) Cohort Study.
AB  - BACKGROUND: Metabolic syndrome is known to increase morbidity and mortality of
      cardiovascular disease. The National Cholesterol Education Program Adult
      Treatment Expert Panel III in 2001 (revised in 2005) and the Japanese definition
      of metabolic syndrome were launched in 2005. No study regarding the association
      between metabolic syndrome by Japanese definition and mortality has been
      performed. The aim of this study was to clarify the prevalence of metabolic
      syndrome and its effects to mortality in a population-based cohort study.
      METHODS: A total of 2,176 subjects who satisfied the necessary criteria for
      metabolic syndrome were examined between 1992 and 1995 as a part of Jichi Medical
      School Cohort Study by Japanese definition. Cox's proportional hazard models were
      used to analyze the association of metabolic syndrome with mortality. RESULTS:
      The prevalence of metabolic syndrome was 9.0% in males and 1.7% in females. There
      were 17 deaths (14 males), including 6 cardiovascular deaths (5 males), during a
      12.5-year follow-up period among metabolic syndrome subjects. After adjusting for
      age, smoking status, and alcohol drinking status, the hazard ratio (95%
      confidence interval) for all-cause mortality was 1.13 (0.64-1.98) in males and
      1.31 (0.41-4.18) in females, and HR for cardiovascular mortality was 1.84 (0.68
      4.96) in males, and 1.31 (0.17-9.96) in females. CONCLUSION: No statistical
      significant relationship between metabolic syndrome by Japanese definition and
      all-cause mortality was observed in a population-based cohort study.

PMID- 18094520
TI  - Comparison of the clinical features of Japanese patients with primary biliary
      cirrhosis in 1999 and 2004: utilization of clinical data when patients applied to
      receive public financial aid.
AB  - BACKGROUND: In Asia there are few reports considering time intervals in the
      examination of clinical features of primary biliary cirrhosis (PBC). Therefore,
      we tried to compare the characteristics of patients with PBC in two different
      years. METHODS: In two fiscal years (1999 and 2004), 9,761 and 13,142 patients
      with symptomatic PBC were registered to receive public financial aid from the
      Ministry of Health, Labour and Welfare of Japan, respectively. For the present
      study, clinical data from 2,127 patients in 1999 and 6,423 ones in 2004 were
      available. We compared the data in the two different years, including sex, age,
      major symptoms, and laboratory data. RESULTS: Male/female ratios were the same
      figure (0.13 for 1999 and 2004). The median age was significantly older in 2004
      than in 1999 (59 years for 1999, 63 years for 2004, respectively, p<0.01).
      Jaundice and esophageal varices were found significantly less frequent in 2004
      than in 1999 (p<0.01 for each item). Levels of total bilirubin,gamma-glutamyl
      transpeptidase (gamma-GTP), total cholesterol, and immunoglobulin M were
      significantly lower in 2004 than in 1999 (p< 0.02 for total bilirubin, and p<0.01
      for other each item). The positive rate of antimitochondrial antibodies was
      significantly higher in 1999 than in 2004 (87.0% for 1999, 83.5% for 2004,
      respectively, p<0.01)). Complicated autoimmune diseases such as Sjogren's
      syndrome, rheumatoid arthritis, and chronic thyroiditis were found significantly
      more frequent in 2004 than in 1999 (p<0.01 for each item). CONCLUSIONS: Among the
      patients with PBC in 2004, an increase in median age, and lower levels of
      laboratory data such as gamma-GTP have been found compared to 1999. These results
      may show an accumulation of patients with better prognosis and the recent medical
      progress in controlling patients with PBC.J Epidemiol 2007; 17: 210-214.

PMID- 18094522
TI  - Prediction of T-cell epitope.
AB  - The prevailing methods to predict T-cell epitopes are reviewed. Motif matching,
      matrix, support vector machine (SVM), and empirical scoring function methods are
      mainly reviewed; and the thermodynamic integration (TI) method using all-atom
      molecular dynamics (MD) simulation is mentioned briefly. The motif matching
      method appeared first and developed with the increased understanding of the
      characteristic structure of MHC-peptide complexes, that is, pockets aligned in
      the groove and corresponding residues fitting on them. This method is now
      becoming outdated due to the insufficiency and inaccuracy of information. The
      matrix method, the generalization of interaction between pockets of MHC and
      residues of bound peptide to all the positions in the groove, is the most
      prevalent one. Efficiency of calculation makes this method appropriate to scan
      for candidates of T-cell epitopes within whole expressed proteins in an organ or
      even in a body. A large amount of experimental binding data is necessary to
      determine a matrix. SVM is a relative of the artificial neural network,
      especially direct generalization of a linear Perceptron. By incorporating non
      binder data and adopting encoding that reflects the physical properties of amino
      acids, its performance becomes quite high. Empirical scoring functions apparently
      seem to be founded on a physical basis. However, the estimates directly derived
      from the method using only structural data are far from practical use. Through
      regression with binding data of a series of ligands and receptors, this method
      predicts binding affinity with appropriate accuracy. The TI method using MD
      requires only structural data and a general atomic parameter, that is, force
      field, and hence theoretically most consistent; however, the extent of
      perturbation, inaccuracy of the force field, the necessity of an immense amount
      of calculations, and continued difficulty of sampling an adequate structure
      hamper the application of this method in practical use.

PMID- 18094523
TI  - Oridonin induced autophagy in human cervical carcinoma HeLa cells through Ras,
      JNK, and P38 regulation.
AB  - In this study, we investigated autophagy induced by oridonin in HeLa cells. HeLa
      cells were exposed to oridonin, and the fluorescent changes, autophagic levels,
      and protein expressions were evaluated. Oridonin induced autophagy in HeLa cells
      in vitro in a dose- and time-dependent manner. Oridonin-treated HeLa cells, which
      had been prelabeled with the autophagosome-specific dye monodansylcadervarine
      (MDC), recruited more MDC-positive particles and had a significantly higher
      fluorescent density; and simultaneously, expressions of autophagy-related
      proteins, MAP-LC3 and Beclin 1, were increased by oridonin. In oridonin-induced
      Hela cells, pretreatment with 3-methyladenine (3-MA, the specific inhibitor of
      autophagy) dose-dependently decreased the autophagic ratio accompanied with
      downregulation of the protein expressions of MAP-LC3 and Beclin 1. Furthermore,
      when a Ras inhibitor was applied, the autophagic levels were augmented, whereas
      P38 and JNK inhibitors decreased the autophagic ratio significantly, indicating
      that this oridonin-induced autophagic process was negatively regulated by Ras,
      but positively regulated by P38 and JNK MAPKs. Raf-1 and ERK1/2 had no obvious
      correlation to these signaling pathways.

PMID- 18094524
TI  - Exposure to extremely low frequency magnetic fields enhances locomotor activity
      via activation of dopamine D1-like receptors in mice.
AB  - We demonstrated that exposure to extremely low frequency magnetic fields (ELF-MF)
      enhanced dopamine levels in the rat striatum. To extend our understanding, we
      examined the role of dopaminergic receptors in ELF-MF-induced behavioral changes.
      Exposure to ELF-MF (2.4 mT, 1 h/day, for one or seven days) enhanced locomotor
      activity in a time-dependent manner. This hyperlocomotor activity paralleled an
      increase in c-Fos-like immunoreactivity (c-Fos-IR). Pretreatment with SCH23390, a
      dopaminergic D(1)-like receptor antagonist, but not with sulpiride, a
      dopaminergic D(2)-like receptor antagonist, inhibited ELF-MF-induced increased
      locomotor activity and c-Fos-IR. Thus, our results suggest that ELF-MF-induced
      behavioral responses are, at least in part, mediated by activation of dopamine
      D(1)-like receptors.

PMID- 18094525
TI  - The OLETF rat as a model of central sensitization: possible relevance to the
      study of fibromyalgia and related diseases.

PMID- 18094526
TI  - Is the OLETF rat a good model of central sensitization?

PMID- 18094527
TI  - Effect of volume of non-surgical embryo transfer medium on ability of porcine
      embryos to survive to term.
AB  - Non-surgical embryo transfer is a promising method for improving efficiency in
      the pork industry and also for biotechnology applications, such as in vitro
      embryo production, transgenesis and cloning. Several groups have reported
      successful piglet production using an artificial insemination catheter or
      flexible catheter designed for this procedure; however, the efficiency of the
      technique is still low. The critical points that need to be addressed in order to
      improve this procedure are (1) the embryo deposition site and (2) volume of
      transfer medium associated with the embryos; however, the latter has not yet been
      examined systematically. In the present study, we evaluated the effect of the
      volume of non-surgical embryo transfer medium on the ability of porcine embryos
      to survive to term by using a recently produced flexible catheter. The catheter
      consists of a guide and an injector. Blastocysts 200-230 mum in diameter were
      collected from donor gilts and transferred to recipient gilts. The time required
      for the completion of embryo transfer using this catheter was 14.6 +/- 3.9 min.
      The tip of the injector was determined by laparotomy to be located in a uterine
      horn 20-30 cm anterior from the branching point of the uterus body. We
      transferred 17.0-17.3 embryos with different volumes of medium (1.6, 3.2 and 10
      ml) into each of 5, 4 and 4 recipients, respectively, and pregnancy was confirmed
      in 4, 3 and 1 of these recipients, respectively. Three recipients in the 1.6 ml
      group farrowed a total of 19 piglets (4, 5 and 10 piglets, respectively). These
      results suggest that successful non-surgical embryo transfer is affected by the
      volume of transfer medium.

PMID- 18094528
TI  - Survival and fertility rate of cooled dromedary camel spermatozoa supplemented
      with catalase enzyme.
AB  - The present study was planned to study the effects of addition of different
      concentrations of catalase enzyme (0, 250, 500 and 1,000 IU/ml) to cooled
      dromedary camel semen extended with tris-yolk-fructose extender on semen quality
      during storage at 5 C for up to 5 days. Conception rates of she-camels
      artificially inseminated with whole fresh or extended cooled dromedary camel
      semen with or without 500 IU/ml catalase enzyme were also estimated. The results
      showed that addition of catalase enzyme at concentrations of 250 or 500 IU/ml to
      extended cooled dromedary camel semen significantly increased (P<0.01) the
      percentage of sperm motility and significantly decreased (P<0.01) the percentages
      of dead spermatozoa, sperm abnormalities and acrosomal damage. The highest
      (P<0.01) percentage of sperm motility was recorded with extended cooled dromedary
      camel semen supplemented with catalase enzyme at a concentration of 500 IU/ml,
      and the lowest (P<0.01) value was recorded with catalase enzyme at a
      concentration of 1000 IU/ml. On the other hand, the lowest (P<0.01) percentages
      of dead spermatozoa, sperm abnormalities and acrosomal damage of spermatozoa were
      recorded with extended cooled dromedary camel semen supplemented with 500 IU/ml,
      and the highest (P<0.01) values were recorded with catalase enzyme at a
      concentration of 1,000 IU/ml. Advancement of the storage time at 5 C
      significantly decreased (P<0.01) the percentage of sperm motility and
      significantly increased (P<0.01) the percentages of dead spermatozoa, sperm
      abnormalities and acrosomal damage of spermatozoa. Moreover, the conception rates
      of she-camels artificially inseminated with whole fresh, extended cooled
      dromedary camel semen free-catalase enzyme and extended cooled dromedary camel
      semen supplemented with catalase enzyme at a concentration of 500 IU/ml were
      46.15, 22.22 and 37.50%, respectively. In conclusion, the results show that
      addition of catalase enzyme at a concentration of 500 IU/ml to semen extender can
      be used as an agent for prolongation of dromedary camel sperm cell survival
      during storage at 5 C.

PMID- 18094529
TI  - Cytochrome c upregulation during capacitation and spontaneous acrosome reaction
      determines the fate of pig sperm cells: linking proteome analysis.
AB  - To identify the mechanisms underlying capacitation, we undertook a high
      resolution differential proteomic analysis of pig sperm cells. Two-dimensional
      gel electrophoresis and subsequent MALDI-TOF mass spectrometry analyses led to
      identification of 56 differentially expressed proteins. After induction of
      capacitation in vitro, the well-established markers of the capacitation
      (lactadherin P47, acrosomal protein SP-10 precursor, prohibitin, proteasomes, DJ
      1 protein and arylsulfatase-A) and TCA cycle proteins (isocitrate dehydrogenase,
      malate dehydrogenase and pyruvate dehydrogenase) were identified. During
      induction, cytochrome c expression via the p53 pathway increased, however
      apoptotic executors, such as caspase-3, decreased significantly. Therefore, we
      tested the hypothesis that cytochrome c upregulation in spermatozoa is capable of
      activating tyrosine phosphorylation for capacitation, rather than apoptosis.
      Exposure of sperm cells to soluble Na2CrO4 [Cr (VI)], which induces cytochrome c
      upregulation, caused a dose- and time-dependent increase in tyrosine
      phosphorylation of sperm proteins in non-capacitating medium. In contrast,
      supplementation of cyclosporin A, which blocks cytochrome c upregulation,
      inhibited tyrosine phosphorylation of sperm proteins. Furthermore, spermatozoa in
      capacitation medium or non-capacitation media supplemented with soluble Cr (VI)
      showed similar levels of capacitation. These findings indicate that differential
      expression of many of these proteins has previously been unrecognized in sperm
      cells incubated in capacitation medium also suggest that a gradual increase of
      cytochrome c during incubation to induce capacitation determines sperm cell fate,
      i.e., apoptosis or further development for fertilization.

PMID- 18094530
TI  - Effects of recloning on the efficiency of production of alpha 1,3
      galactosyltransferase knockout pigs.
AB  - Obtaining sufficient transgenic cells via selective cultivation of genetically
      manipulated somatic cells is difficult due to the limited number of cell
      divisions. Additionally, if irreversible mutations in a cell's chromosomes occur
      during selective cultivation and the cell is used as the nuclear donor, somatic
      cell nuclear transfer (SCNT) embryos often exhibit abnormal development. On the
      other hand, a SCNT method in which fetal cells derived from SCNT embryos are used
      as the nuclear donor (recloning method) is an effective technique for obtaining
      large quantities of transgenic cells. In this study, we compared the in vivo
      development rate of SCNT embryos produced from porcine alpha1-3
      galactosyltransferase gene knockout (GTKO) cells by a recloning method with that
      of SCNT embryos produced without recloning from porcine GTKO cells (direct
      method). In the direct method, 557 and 462 cloned embryos were produced using two
      types of activation methods, the two-step activation (TA) method and the delayed
      activation (DA) method, and then transferred into 6 and 4 recipients,
      respectively, but no piglets were born from these recipients. In the recloning
      method, 956 and 1038 cloned embryos were produced using the TA and DA methods,
      respectively, and then transferred to 8 and 7 recipients, respectively. Two
      piglets were born from one recipient in the TA group and 6 piglets were born from
      3 recipients in the DA group. This report indicates that the recloning method
      improved the developmental capacity of SCNT embryos reconstructed with gene
      targeted somatic cells.

PMID- 18094531
TI  - Allopurinol gel mitigates radiation-induced mucositis and dermatitis.
AB  - It has not been verified whether allopurinol application is beneficial in
      decreasing the severity of radiation-induced oral mucositis and dermatitis. Rats
      were divided into 4 groups and received 15 Gy irradiation on the left whisker
      pad. Group 1 received only irradiation. Group 2 was maintained by applying
      allopurinol/carrageenan-mixed gel (allopurinol gel) continuously from 2 days
      before to 20 days after irradiation. Group 3 had allopurinol gel applied for 20
      days after radiation. Group 4 was maintained by applying carrageenan gel
      continuously from 2 days before to 20 days after irradiation. The intra oral
      mucosal and acute skin reactions were assessed daily using mucositis and skin
      score systems. The escape thresholds for mechanical stimulation to the left
      whisker pad were measured daily. In addition, the irradiated tissues at the
      endpoint of this study were compared with naive tissue. Escape threshold in group
      2 was significantly higher than that in group 1, and mucositis and skin scores
      were much improved compared with those of group 1. Concerning escape threshold,
      mucositis and skin scores in group 3 began to improve 10 days after irradiation.
      Group 4 showed severe symptoms of mucositis and dermatitis to the same extent as
      that observed in group 1. In the histophathological study, the tissues of group 1
      showed severe inflammatory reactions, compared with those of group 2. These
      results suggest that allopurinol gel application can mitigate inflammation
      reactions associated with radiation-induced oral mucositis and dermatitis.

PMID- 18094532
TI  - Interleukin-17 as an effector molecule of innate and acquired immunity against
      infections.
AB  - Interleukin (IL)-17 is a proinflammatory cytokine which induces differentiation
      and migration of neutrophils through induction of cytokines and chemokines
      including granulocyte-colony stimulating factor and CXCL8/IL-8. IL-17-producing
      CD4(+) T cells (Th17) have pivotal role in pathogenesis of autoimmune diseases.
      IL-17 is also involved in protective immunity against various infections. IL-17
      has important role in induction of neutrophil-mediated protective immune response
      against extracellular bacterial or fungal pathogens such as Klebsiella pneumoniae
      and Candida albicans. Importance of IL-17 in protection against intracellular
      pathogens including Mycobacterium has also been reported. Interestingly, not only
      CD4(+) T cells but atypical CD4(-)CD8(-) T cells expressing T cell receptor (TCR)
      gammadelta produce IL-17, and IL-17 producing cells participate in both innate
      and acquired immune response to infections. Furthermore, neutrophil induction may
      not be the only mechanism of IL-17-mediated protective immunity. IL-17 seems to
      participate in host defense through regulation of cell-mediated immunity or
      induction of antimicrobial peptides such as beta-defensins. In this review, we
      summarize recent progress on the role of IL-17 in immune response against
      infections, and discuss possible application of IL-17 in prevention and treatment
      of infectious diseases.

PMID- 18094533
TI  - Reliable enzyme-linked immunosorbent assay systems for pathogenic factors of
      Pseudomonas aeruginosa alkaline proteinase, elastase, and exotoxin A: a
      comparison of methods for labeling detection antibodies with horseradish
      peroxidase.
AB  - Sensitive sandwich enzyme-linked immunosorbent assay (ELISA) systems for the
      quantification of 3 pathogenic factors of Pseudomonas aeruginosa-alkaline
      proteinase (aeruginolysin), elastase (pseudolysin ), and exotoxin A-were
      developed. The maleimide-pyridyl disulfide method was applied for the labeling of
      rabbit anti-each antigen IgG with horseradish peroxidase (HRP) and the conjugates
      were used as secondary antibodies (detection antibodies) in the ELISA systems.
      The EDTA, a chelating agent, was added to the buffers for sample and detection
      antibody, which inhibited the degradation of IgG by elastase derived from P.
      aeruginosa for improving the assay precision. The ELISA systems using the HRP
      labeled detection antibodies produced by the maleimide-pyridyl disulfide method
      exhibited higher sensitivity than previously reported methods. The detection
      limits for alkaline proteinase, elastase, and exotoxin A were 18 pg/ml, 34 pg/ml,
      and 22 pg/ml, respectively. The intra-assay coefficients of variation for
      alkaline proteinase, elastase, and exotoxin A were 3.4%-5.0%, 1.9%-3.5%, and 1.3%
      5.4%, respectively. These ELISA systems exhibited good inter-assay precision, non
      cross-reactivity, dilution linearity, and recovery . Employing these ELISA
      systems, we revealed that pathogenic factor concentrations were different among
      the P. aeruginosa strains tested, which may relate to the different pathogenicity
      of each strain.

PMID- 18094534
TI  - Evasion of Legionella pneumophila from the bactericidal system by reactive oxygen
      species (ROS) in macrophages.
AB  - We demonstrated that the production of reactive oxygen species (ROS) by U937
      macrophage-like cells was suppressed upon infection with a wild type Legionella
      pneumophila strain, whereas such suppression was not observed in the case of
      infection with intracellular growth-deficient mutants. This was supported not
      only by measuring ROS released into the supernatants of cell cultures by
      chemiluminescence assaying but also by detecting intracellular ROS with a
      fluorescent probe, 2-[6-(4'-amino)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid
      (APF), under a confocal laser scanning microscope. Furthermore, more than 60% of
      the phagosomes containing intracellular growth-deficient mutants were colocalized
      with p47(phox), which is the cytosolic subunit of NADPH oxidase, consistently
      throughout the observation period in an early stage of bacterial infection. In
      contrast, the colocalization of p47(phox) was suppressed after infection with the
      wild type strain. These results suggest that the interference with ROS production
      by U937 cells infected with wild type L. pneumophila is due to a failure of NADPH
      oxidase activation through inhibition of p47(phox) recruitment to phagosomes
      harboring bacteria. The results also highlighted the difference in the nature of
      phagosomes between ones harboring the wild type and ones the intracellular growth
      deficient strains.

PMID- 18094535
TI  - Comparative proteome analysis of the outer membrane proteins of in vitro-induced
      multi-drug resistant Neisseria gonorrhoeae.
AB  - Antimicrobial-resistant gonococcus has been a major problem in sexually
      transmitted disease control . Outer membrane proteins (OMPs) of Neisseria
      gonorrhoeae were suggested to have influence on its resistance to antibiotics.
      So, in this work, we provide a proteomic analysis tool for examining the OMPs of
      N. gonorrhoeae and also provide a comparative analysis of the OMPs between the
      susceptible parent strain (92WT) and the resistance-induced isogenic mutant
      (92mu13) to determine the OMPs responsible for resistance. The 2-D gel spots of
      92mu13 differed from 92WT particularly in porin, pilus secretion protein (PilQ)
      and enzymes. PilQ expression in 92mu13 was considerably reduced by abrupt
      termination at nucleotide 2,112. This made it difficult to form a high molecular
      mass (HMM) pore at the outer membrane; it is suspected that reduction of PilQ
      serves a role in antibiotic resistance in N. gonorrhoeae. The amount of porin was
      not changed but its isoelectric point (pI) shifted to a basic region, which is
      caused by the alteration of an amino acid of porin and it is suggested to relate
      to the development of antimicrobial resistance . Differential regulation of the
      enzymes involved in metabolism was found in 92mu13, believed to represent an
      adaptation of N. gonorrhoeae to the antibiotic environment.

PMID- 18094536
TI  - Comparison of epitope structures of H3HAs through protein modeling of influenza A
      virus hemagglutinin: mechanism for selection of antigenic variants in the
      presence of a monoclonal antibody.
AB  - Starting with nine plaques of influenza A/Kamata/14/91(H3N2) virus, we selected
      mutants in the presence of monoclonal antibody 203 (mAb203). In total, amino acid
      substitutions were found at nine positions (77, 80, 131, 135, 141, 142, 143, 144
      and 146), which localized in the antigenic site A of the hemagglutinin (HA). The
      escape mutants differed in the extent to which they had lost binding to mAb203.
      HA protein with substitutions of some amino acid residues created by site
      directed mutagenesis in the escape mutants retained the ability to bind to
      mAb203. Changes in the amino acid character affecting charge or hydrophobicity
      accounted for the binding capacity to the antibody of the HA with most of the
      substitutions in the escape mutants and binding-positive mutants. However, the
      effect of some amino acid substitutions remained unexplained. A three-dimensional
      model of the 1991 HA was constructed and used to analyze substituted amino acids
      in these mutants for the accessible surface hydrophobic and hydrophilic
      characters. One amino acid substitution in an escape mutant and another amino
      acid substitution in a binding-positive mutant seemed to be explained by the
      changes noted on this model.

PMID- 18094537
TI  - Decrease in CD93 (C1qRp) expression in a human monocyte-like cell line (U937)
      treated with various apoptosis-inducing chemical substances.
AB  - Human CD93, a receptor for complement component 1, subcomponent q phagocytosis
      (C1qRp), has been shown to be selectively expressed by cells of a myeloid lineage
      and was originally reported to be involved in the C1q-mediated enhancement of
      phagocytosis in innate and adaptive immune responses. The modulation of CD93
      expression has been investigated in various cells, particularly in granulocytes
      and monocytes . We previously reported that a protein kinase C activator (PKC),
      phorbol myristate acetate (PMA), effectively up-regulated CD93 expression on
      several cultured cell lines and that its regulation was mainly controlled by a
      PKC delta-isoenzyme. However, the expression pattern of CD93 in myeloid cells
      with apoptotic properties remains poorly understood. In this study, we examined
      the modulation of CD93 expression on a human monocyte-like cell line (U937)
      treated with various apoptosis-inducing chemical substances : an RNA-synthesis
      inhibitor, actinomycin D (ActD); a DNA topoisomerase I inhibitor, camptothecin
      (CPT); a protein-synthesis inhibitor, cycloheximide (CHX); a DNA topoisomerase II
      inhibitor, etoposide (EPS); and a DNA-synthesis inhibitor, mitomycin C (MMC).
      Apoptosis was monitored using two-color flow cytometry with Annexin V and 7-amino
      actinomycin D (7AAD). The above-mentioned substances sufficiently induced the
      early and late stages of apoptosis, identified as Annexin V positive (+)/7AAD
      negative (-) cells and Annexin V positive (+)/7AAD positive (+) cells,
      respectively, in U937 cells after 6 hr of treatment. The modulation of CD93
      expression on U937 cells during the early stage of apoptosis, gated as Annexin V
      positive (+)/7AAD negative (-) cells, was then investigated using a CD93 mAb (mNI
      11), originally established in our laboratories, and flow cytometry using a
      fluorescence-activated cell sorter (FACS). The mean fluorescence intensity (MFI)
      of the cells that stained positive for CD93 mAb (mNI-11) among the treated U937
      cells showed a dramatic decrease in expression. In addition, the expressions of
      HLA-class I (HLA-A, B, C), HLA-class II (HLA-DR), CD18 (lymphocyte function
      associated antigen-1 beta; LFA-1beta) and CD54 (intercellular adhesion molecule
      1; ICAM-1) were also markedly decreased on the treated U937 cells identified as
      Annexin V positive (+)/7AAD negative (-) cells (early stage of apoptosis).
      Interestingly, the expression patterns of CD93 on the U937 cells treated with the
      above-mentioned chemical substances closely resembled those of HLA-class I (HLA
      A, B, C). An immunoblotting analysis showed that the expression of a surface
      antigen (molecular size, about 97 kDa) targeted by the CD93 mAb (mNI-11) on the
      U937 cells treated with various apoptosis-inducing chemical substances had
      clearly decreased. On the other hand, an enzyme-linked immunoassay (EIA) showed
      that although PMA-treated U937 cells had strongly secreted soluble CD93 (sCD93)
      into the culture supernatant, the secretion of sCD93 in the culture supernatant
      of the U937 cells treated with the above-mentioned chemical substances was not
      enhanced, compared with that of untreated U937 cells. Importantly, however , the
      U937 cells with apoptotic properties induced by various apoptosis-inducing
      chemical substances also rapidly (in 30 min) and strongly secreted sCD93 into the
      culture supernatant in the presence of PMA. Taken together, these findings
      indicate that the expression of the CD93 molecule identified by CD93 mAb (mNI-11)
      is dramatically decreased on U937 cells with apoptotic properties, and that the
      decrease in CD93 expression on U937 cells treated with apoptosis-inducing
      chemical substances may be a good model for analyzing the regulation of CD93
      expression on apoptotic myeloid cells.

PMID- 18094538
TI  - First molecular detection of Borrelia afzelii in clinical samples in Korea.
AB  - Borrelia afzelii nucleic acids were detected in the sera of febrile disease
      patients by a nested PCR that targeted the rrf (5S)-rrl (23S) spacer of B.
      burgdorferi sensu lato. The B. afzelii-specific DNA fragment was detected in 8
      out of 283 sera which were proven to have immunoglobulin G or M antibodies
      against B. burgdorferi antigens through IFA. The results were further confirmed
      through restriction fragment length polymorphism and sequencing analysis of the
      DNA fragments. The results indicated for the first time that Lyme borreliosis is
      prevalent in Korea.

PMID- 18094539
TI  - Comparative role of antibiotic and proton pump inhibitor in experimental
      Clostridium difficile infection in mice.
AB  - Clostridium difficile inoculated BALB/c mice were investigated to assess the
      comparative role of antibiotic and proton pump inhibitor. They were examined for
      colonization and toxin production by C. difficile as well as myeloperoxidase
      activity and histopathological changes in the intestinal tract. The C. difficile
      count, toxin A and B titres and myeloperoxidase activity were significantly
      higher (P>0.05) in ampicillin and lansoprazole receiving groups as compared to
      the control and the C. difficile receiving groups. Similarly they showed
      significant difference (P >0.05) for epithelial damage, oedema and neutrophilic
      infiltrate in colons. In addition to antibiotic, PPI also acts as an independent
      risk factor for C. difficile infection in experimental studies.

PMID- 18094540
TI  - Analysis of risk epitopes of anti-neutrophil antibody MPO-ANCA in vasculitis in
      Japanese population.
AB  - Autoantibodies to myeloperoxidase (MPO) are a subset of anti-neutrophil
      cytoplasmic antibody (ANCA, MPO-ANCA) detected in the sera of some patients with
      primary systemic vasculitis. The titer of MPO-ANCA does not always reflect
      disease activity and this inconsistency may be attributable to differences in
      epitopic specificity by MPO-ANCA among various patients with vasculitis. Epitope
      analysis may also explain the occurrence of MPO-ANCA in different vasculitic
      syndromes. We screened the sera of 148 MPO-ANCA positive patients from six
      vasculitic syndromes: rapidly progressive gromerulonephritis (RPGN), microscopic
      polyangiitis (MPA), idiopathic crescentic glomerulonephritis (I-CrGN), classic
      polyangiitis nodosa (cPAN), Churg-Strauss syndrome (CSS), Kawasaki disease (KD);
      and from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus
      (SLE). The sera were collected by the Intractable Vasculitis Research Project
      Group in Japan. No serum showed epitopes La and Lb of light chain of MPO, and
      sera with 68.6% of patients showed a positive reaction to one or more epitopes in
      heavy chain of MPO. Analysis of binding level showed that RPGN, I-CrGN and MPA
      sera mainly reacted to the Ha epitope at the N-termimus of the MPO heavy chain,
      CSS sera reacted to Ha and the Hf epitope close to the C-terminus of the MPO
      heavy chain, KD reacted mainly to Hf, while SLE and RA sera reacted to all
      epitopes. These results suggest that MPO-ANCA recognizing specific regions of the
      N-terminus of the MPO H-chain confer an increased risk of vasculitis RPGN, I
      CrGN, MPA and CSS. Furthermore, the epitopic specificity of MPO-ANCA
      differentiates vasculitic from non-vasculitic syndromes associated with MPO-ANCA
      positivity and differentiates in the cirtain type of vasculitis from various
      vasculitic syndromes. In particular, vasculitic syndromes associated with kidney
      involvement had similar epitopic reactivity which suggests that this pattern
      confers an increased risk of vasculitis.

PMID- 18094541
TI  - A potential blood test for transmissible spongiform encephalopathies by detecting
      carbohydrate-dependent aggregates of PrPres-like proteins in scrapie-Infected
      hamster plasma.
AB  - PrPres has rarely been detected in blood (except in leukocytes) even in diseased
      animal models that are known to contain a large amount of PrPres in infected
      tissues. It seems likely that PrPres detection in blood is difficult because of
      the low titer of infectious material within the blood. Here, we demonstrate the
      detection of proteinase K-resistant 3F4-reactive protein in the plasma of scrapie
      infected hamsters but not in the plasma of mock-infected hamsters by partial
      purification using a novel method termed "acidic SDS precipitation," in
      conjunction with a highly sensitive chemiluminescence detection system used to
      show the presence of PrP at a concentration equivalent to 1.4x10(-9) g of brain
      homogenate or 1.5x10(-12) g (6.5x10(-17) mol) of rPrP by conventional Western
      blotting. The 3F4-reactive proteins in scrapie-infected hamster plasma often
      resulted in multiple Mw protein bands occurring at higher Mw positions than the
      position of the di-glycosyl PrP molecule. Mixing scrapie-infected hamster brain
      homogenate with mock-infected hamster plasma resulted in the formation of similar
      Mw positions for multiple 3F4-reactive proteins. Predigestion of carbohydrate
      side chains from the proteins in the plasma or brain homogenate before mixing
      resulted in failure to obtain these multiple 3F4-reactive proteins. These
      observations indicate that PrPres aggregated with other proteins in the plasma
      through carbohydrate side chains and was successfully detected in the plasma of
      scrapie-infected hamsters. Counterparts in these aggregates with PrPres-like
      proteins in scHaPl are not known but any that exist should resist the PK
      digestion.

PMID- 18094542
TI  - [Clinical usefulness of the simple technique to diagnose thrombocytopenia using
      immature platelet fraction].
AB  - BACKGROUND: Immature platelet fraction (IPF) is the percentage of reticulated
      platelet (RP) of total platelet count. We measured an IPF reference range using
      XE-2100 blood cell counter with upgraded software (Sysmex, Japan) and evaluated
      the clinical utility of this parameter for the laboratory diagnosis of
      thrombocytopenia due to an increase in peripheral platelet destruction. METHODS:
      Peripheral blood samples collected into K2EDTA (Beckton Dickinson, USA) were
      analyzed at Chonbuk National University Hospital. One hundred forty-two samples
      from apparently healthy adults (all routine full blood count parameters including
      platelets within the healthy reference range) were used to establish a normal
      reference range for IPF. The patients were classified into 3 groups including
      hypoplastic (consisted of 22 patients undergoing chemotherapy with falling
      platelet counts and 14 with aplastic anemia), cirrhotic (40 with cirrhosis of
      liver), and idiopathic thrombocytopenic purpura (ITP) (14 with ITP) groups.
      RESULTS: An IPF reference range in healthy individuals was established as 0.4
      5.4%, with a mean of 1.7%. A significant increase in IPF values was found in the
      ITP patient group. The cut-off value of IPF was 6.1% and its sensitivity and
      specificity were 92.9%, and 82.9% respectively. Reproducibility was good.
      CONCLUSIONS: A rapid, inexpensive automated method for measuring IPF is feasible
      and should become a standard parameter in evaluating thrombocytopenic patients.

PMID- 18094543
TI  - [Comparison of an immature platelet fraction and reticulated platelet in liver
      cirrhosis].
AB  - BACKGROUND: The main causes of thrombocytopenia in cirrhosis are thought to be
      platelet destruction and the reduction of thrombopoietin (TPO) expression in the
      liver. Immature platelet fraction (IPF) has been measured by a fully automated
      analyzer (Sysmex XE-2100, Japan) as reticulated platelet (RP), which is reflected
      with thrombopoiesis in bone marrow. In this study, we tried to compare the
      percentage of IPF (IPF) with that of RP (RP) in patients with liver cirrhosis
      (LC) and controls. METHODS: We compared IPF to RP in 72 liver cirrhosis patients
      and 30 healthy normal controls. RP was stained with acridine orange, followed by
      FC500 (Beckman Coulter, USA) analysis and the IPF was identified by flow
      cytometry with the use of a nucleic acid specific dye in the reticulocyte channel
      on the Sysmex XE-2100 (TOA Medical Electronics Co., Ltd., Japan). RESULTS: IPF
      value in the healthy control was 2.2% (1.7-5.2). RP and IPF were significantly
      higher in the patients with liver cirrhosis (P<0.05). IPF appeared to be
      correlated with RP (y=0.19x+3.35, r=0.34, P<0.05). In ROC for diagnosis of LC,
      IPF was significantly more useful than RP. CONCLUSIONS: This results show that a
      rapid, inexpensive automated method for measuring the IPF is feasible and should
      become a standard parameter in evaluating reticulated platelets.

PMID- 18094544
TI  - [Clinical significance of reticulocyte maturation parameters in the differential
      diagnosis of macrocytic anemias].
AB  - BACKGROUND: Macrocytic anemias are commonly seen in clinical practice, and
      precise etiologic diagnosis is essential for proper management. We evaluated the
      clinical utility of reticulocyte maturation parameters in macrocytic anemias to
      discriminate among myelodysplastic syndrome (MDS), megaloblastic anemia (MA), and
      non-megaloblastic macrocytic anemia associated with chronic liver disease (MA
      CLD). METHODS: Using an automated reticulocyte counter, we retrospectively
      analyzed and compared reticulocyte maturation parameters including immature
      reticulocyte fraction (IRF), mean reticulocyte volume (MRV), mean sphered cell
      volume (MSCV) of normal control (N=34), and patients diagnosed with MDS (N=31),
      MA (N=52), and MA-CLD (N=196). RESULTS: Macrocytic anemias from MA, MDS and MA
      CLD showed higher values of reticulocyte maturation parameters including IRF, MRV
      and MSCV than normal control (P<0.01). MDS showed higher values of reticulocyte
      maturation parameters including IRF, MRV and MSCV than MA-CLD (P<0.01). IRF and
      MRV were significantly lower in MA-CLD than in both MA and MDS (P<0.01). MSCV was
      significantly higher in MDS than in MA (P<0.01). CONCLUSIONS: This study
      indicates that the measurement of reticulocyte maturation parameters may be a
      useful tool in the differential diagnosis of macrocytic anemia. The presence of
      high values of IRF (> or = 0.39), MRV (> or = 129.5 fL), and MSCV (> or = 102.3
      fL) makes the diagnosis of MA-CLD unlikely and underlying MDS should be
      considered.

PMID- 18094545
TI  - [A case of therapy-related acute myeloid leukemia associated with inv(16)].
AB  - The inv(16)(p13q22) is found in de novo AML and is closely associated with the
      FAB subtype M4eo. The inv(16) is rarely reported in therapy-related AML (t-AML)
      patients. Herein, we report a case of t-AML with inv(16) after combination
      chemotherapy using antimitotic agent and alkylating agent (cis-platin-paclitaxel)
      for ovarian serous cystadenocarcinoma.

PMID- 18094546
TI  - [Usefulness of NMP22 BladderChek for the diagnosis and monitoring of bladder
      cancer].
AB  - BACKGROUND: As bladder cancer is a superficial tumor with frequent recurrences,
      early detection and confirmation of recurrence are important. We evaluated the
      usefulness of NMP22 BladderChek (NMP22BC) for the diagnosis and monitoring of
      bladder cancer. METHODS: From July to December 2004, we enrolled in the study 670
      patients who visited the urology clinic in Ewha Womans University, Dongdaemun
      Hospital with hematuria or dysuria and were tested with NMP22BC. We also
      performed the NMP22BC and BTA stat tests simultaneously in 21 patients and
      interference test in 10 patients. RESULTS: NMP22BC tests were negative in 97% of
      the patients who had been cured of bladder cancer and were positive in 95% of the
      patients with recurred bladder cancer. The diagnostic sensitivity, specificity,
      positive and negative predictive value, and efficiency were 95.0%, 91.5%, 25.7%,
      99.8%, and 91.6%, respectively, with 8.5% false positive and 5% false negative
      rates. Fifty-five patients showed false positive in the NMP22BC test, the main
      cause of which was the presence of WBCs in urine. There was a good agreement
      between the NMP22BC and BTA stat tests (kappa agreement value, 0.5; P=0.008).
      According to the interference test, two patients with more than 3+ in leukocyte
      esterase results showed false positive in the NMP22BC test. CONCLUSIONS: NMP22BC
      test was simple to perform, rapid to produce the results, and useful in
      diagnosing a bladder cancer recurrence; the test shows a high efficiency with a
      high sensitivity, specificity, negative predictive value, and low false negative
      rate.

PMID- 18094547
TI  - [Prenatal serum marker screening in Korea: survey results].
AB  - BACKGROUND: Maternal serum triple marker screening has been covered by the
      medical insurance system in Korea since December 2004. The number of tests is on
      the increase, but an external quality control program and a basic survey have not
      been established yet. The aim of this study was to port the survey of prenatal
      screening tests. METHODS: Three different quality control specimens were prepared
      using the sera obtained from 100 women who were in the 15th to 20th week of
      pregnancy and visited Asan Medical Center during May 2005. We assumed that the
      three specimens belonged to the first day of 15 weeks, third day of 16 weeks, and
      second day of 19 weeks, respectively, and sent them to 10 laboratories. Nine
      laboratories replied to the survey. We analyzed concentrations, multiples of
      medians (MoMs), and risk estimates. RESULTS: The coefficients of variance of MoM
      were 32.1-32.6% for alpha-fetoprotein, 15.3-19.8% for unconjugated estriol, 6.3
      12.5% for human chorionic gonadotropin, and 12.9-18.2% for inhibin-A. In Down
      syndrome risk estimation for specimen-2, six of the eight laboratories that used
      the triple test reported the screen positive, but two laboratories reported
      negative. Three of five laboratories using the quadruple test reported the screen
      positive, and two laboratories reported negative. In case of neural tube defect,
      all laboratories except one reported all specimens the screen negative. In case
      of Edward syndrome, all laboratories reported all specimens the screen negative.
      CONCLUSIONS: Since MoMs and risk estimates showed a wide variation among the
      participating laboratories in this survey, an external quality control and the
      standardization of the variables seemed warranted.

PMID- 18094548
TI  - [Assessment of the accuracy and precision of cystatin C-based GFR estimates and
      Cr-based GFR estimates in comparison with Cr51-EDTA GFR].
AB  - BACKGROUND: Cystatin C (cysC) is said to be an ideal marker for glomerular
      filtration rate (GFR), independent of external factors such as age, nutrition and
      inflammation. The authors compared the accuracy and precision of cysC-based and
      creatinine (Cr)-based GFR estimates using Cr51-EDTA GFR method as a reference.
      METHODS: Serum concentrations of cysC and Cr were measured in adults over 17 yr
      (n=170) and children below 17 yr (n=79) who had had GFR estimated by Cr51-EDTA
      method. CysC-based GFR was estimated by the formula of Thierry [CysC-based GFR
      estimates (mL/min/1.73 m2)=78 x (1/cysC, in mg/L)+4] and Cr-based GFR by the
      formula of modified Modification of Diet in Renal Disease [MDRD II, Cr-based GFR
      estimates (mL/min/1.73 m2)=186 x (Scr)(-1.154) x (Age)(-0.203) x 0.742 (for a
      female patient) x 1.212 (for a black patient). RESULTS: In comparison with Cr51
      EDTA GFR, in children below 17 yr, the bias +/- standard deviation (SD) of cysC
      based and Cr-based GFR estimates were 7.5 +/- 6.1 and 106.5 +/- 98.2,
      respectively, in the range of below 90 of Cr51-EDTA GFR (mL/min/1.73 m2), and
      33.7 +/- 33.0 and 174.4 +/- 18.8 in the range of over 90. In adults over 17 yr,
      the respective figures were 13.1 +/- 11.0 and 17.4 +/- 29.8 in below 90, and 21.2
      +/- 20.1 and 83.6 +/- 108.8 in over 90 of Cr51-EDTA GFR. CONCLUSIONS: CysC-based
      GFR estimates show acceptable ranges of biases over the whole age and GFR ranges.
      CysC-based GFR estimates is considered to be the marker for GFR, which could be
      used without limitation of age and GFR ranges.

PMID- 18094549
TI  - [Usefulness of multiplex real-time PCR and melting curve analysis in
      identification of nontuberculous mycobacteria].
AB  - BACKGROUND: Nontuberculous mycobacteria (NTM) should be correctly identified to
      the species level, because of different treatment plans among NTM species. This
      study was performed to assess the usefulness of real-time PCR and melting curve
      analysis in the identification of NTM. METHODS: One hundred fifty-two clinical
      NTM isolates were identified to the species level by PCR-restriction fragment
      length polymorphism analysis (PRA). Those strains were then identified by
      multiplex real-time PCR and melting curve analysis on the 16S rRNA gene and hsp65
      gene. RESULTS: In the 16S rRNA gene fragment analysis, M. abscessus-M. chelonae
      group showed melting point at temperatures above 65 degrees C and M. avium
      complex (MAC; M. avium and M. intracelluare) below 48 degrees C, which
      differentiated M. abscessus-M. chelonae group and MAC from other NTM. In the
      hsp65 gene fragment analysis, M. abscessus-M. chelonae group was clearly divided
      into M. abscessus type I, M. abscessus type II, and M. chelonae according to the
      melting points at 61.25 degrees C, 66.06 degrees C, and 57.58 degrees C,
      respectively. CONCLUSIONS: With the multiplex real-time PCR and melting curve
      analysis of 16S rRNA and hsp65 genes, M. abscessus and M. chelonae were readily
      identified and MAC were differentiated from other NTM. Especially, M. abscessus
      and M. chelonae, which were not differentiated from each other with the 16S rRNA
      gene fragment analysis, were identified with hsp65 gene fragment analysis.

PMID- 18094550
TI  - [A case of erythromycin-resistant Ureaplasma urealyticum meningitis in a
      premature infant].
AB  - Ureaplasma urealyticum causes infection or colonization of female genital tracts
      associated with preterm delivery and infertility and the infection of the
      bloodstream, respiratory tract, and central nervous system in infants, especially
      in prematures. We report the first case of U. urealyticum meningitis in a
      premature infant in Korea. She was born with a birth weight of 1,481 gram at 32+3
      weeks' gestation and hospitalized for a respiratory care in the NICU in November
      2005. Endotracheal aspirates and urine cultures grew U. urealyticum at <10(4)
      CFU/mL of the specimens at 2-day-old, and cerebrospinal fluid (CSF) cultures grew
      U. urealyticum at > or = 10(4) CFU/mL of CSF. The patient had a marked CSF
      pleocytosis, low glucose and high protein content on the 13th hospital day. CSF
      cultures for ordinary bacteria, mycobacteria and fungi remained negative. U.
      urealyticum was resistant to erythromycin, tetracycline, ciprofloxacin and
      pristinamycin, but susceptible to doxycycline. Although she was treated with
      erythromycin for 30 days, the organism was still isolated four times from the CSF
      with fluctuation of C-reactive protein (CRP). After the addition of
      chloramphenicol, CSF cultures became negative in 3 days. However, CRP rose again
      with increased BUN at the 99th hospital day, and she died on the 103rd hospital
      day under the diagnosis of a clinical sepsis of unknown origin. In acute
      meningitis of prematures already colonized with U. urealyticum, ureaplasmal
      cultures and susceptibility test are warranted in Korea.

PMID- 18094551
TI  - [Comparison of the urine ThinPrep test and melanoma antigen gene RT-PCR for the
      detection of bladder cancer according to three urine collection methods].
AB  - BACKGROUND: For the detection of transitional cell carcinoma (TCC) of the
      bladder, we compared the sensitivities and specificities between the ThinPrep
      test and Melanoma Antigen Gene (MAGE) test with voided urine (V), drained urine
      (D), and irrigated urine (I). METHODS: We randomly selected 10 patients of a non
      cancer group and 20 patients of a cancer group. V, D, and I were obtained
      preoperatively, and equally divided into two parts for the ThinPrep test and MAGE
      reverse transcriptase polymerase chain reaction (RT-PCR). The cystoscopic finding
      was used as the reference standard for detection of bladder cancer. The results
      of ThinPrep test and MAGE RT-PCR were compared according to cancer grade and
      stage. RESULTS: The overall sensitivities of ThinPrep test were 45%, 85% and 85%
      for V, D, and I, respec-tively, while those of MAGE test were 50%, 85%, and 65%.
      Detection rate from drainage urine was considerably higher than that of voided
      urine in both methods (P<0.05). The specificities were 100% for all types of
      urine specimens with ThinPrep test and 100%, 90%, and 90% for V, D, and I,
      respectively, using MAGE test, without any statistically significant differences.
      CONCLUSIONS: For the detection of bladder cancer, MAGE RT-PCR and ThinPrep test
      showed a comparable sensitivity and specificity, and drained urine revealed the
      best detection rate. MAGE RT-PCR might be utilized as another marker of bladder
      cancer using urine specimens.

PMID- 18094552
TI  - [Incidence and clinical significance of sex chromosome losses in bone marrow of
      patients with hematologic diseases].
AB  - BACKGROUND: Loss of sex chromosomes in bone marrow is observed both in elderly
      persons as an aging phenomenon and in patients with hematologic malignancies. The
      purpose of this study was to evaluate the incidence and clinical significance of
      sex chromosome losses in patients with hematologic diseases, comparing the
      characteristics between patients with sole and secondary sex chromosome losses in
      conjunction with other chromosomal abnormalities. METHODS: Study group included
      868 patients with hematologic diseases between June 1998 and May 2006. The cells
      of bone marrow aspirates were processed using unstimulated culture methods such
      as direct, 24-hr and/or 48-hr culture. Sex chromosome losses were included in the
      karyotype, when X or Y chromosome loss is observed in more than 2 metaphase
      cells. RESULTS: The sex chromosome losses in bone marrow were found in 5.1% of
      the patients and 1.8% showed sex chromosome losses as a sole chromosomal
      abnormality. According to the disease categories, the incidences of sex
      chromosome losses were as follows: acute myelogenous leukemia (AML), 9.5%; acute
      lymphoblastic leukemia, 0%; myelodysplastic syndrome, 6.0%; chronic myelogenous
      leukemia 3.6%; myeloproliferative disorders, 1.3%; multiple myeloma (MM), 13.0%;
      chronic lymphocytic leukemia, 0%; malignant lymphoma, 3.8%; and benign
      hematologic diseases 2.2%. The patients with sex chromosome losses as a sole
      chromosomal abnormality were all male and median age was higher than that of
      patients with sex chromosome losses as a secondary abnormality (64 vs. 58 yr,
      P=0.02). The proportion of metaphase cells with sex chromosome losses was
      significantly lower in patients with sex chromosome losses as a sole chromosomal
      abnormality (40% vs. 100%, P<0.0001). The changes of sex chromosome loss were
      correlated with the disease status of AML and MM. CONCLUSIONS: These results
      suggest that secondary sex chromosome losses in conjunction with other
      chromosomal abnormalities seem to be one of the clonal abnormalities, whereas sex
      chromosome losses as a sole change seem to be an aging phenomenon, but further
      studies are needed.

PMID- 18094553
TI  - [Human papilloma virus genotyping assay using restriction fragment mass
      polymorphism analysis, and its comparison with sequencing and hybrid capture
      assays].
AB  - BACKGROUND: Infection with human papilloma virus (HPV) is the main cause of
      cervical cancer, and HPV genotyping is of increasing importance for determining
      clinical course and management of the disease based on the HPV genotypes. Here,
      we established a novel matrix-assisted laser desorption/ ionization time of
      flight mass spectrometry (MALDI-TOF MS) assay, termed restriction fragment mass
      polymorphism (RFMP) that is suitable for genotyping multiple HPV in an accurate
      and high-throughput manner. We evaluated the performance of the RFMP assay in HPV
      genotyping by comparing the results with those of direct or clonal sequencing and
      hybrid capture (HC) assays. METHODS: The study population consisted of 50
      patients with histologically confirmed cervical lesions and a positive test for
      HPV DNA. HPV genotyping was performed with RFMP, sequencing, and HC assays. The
      assigned genotypes and risk groups were compared among the methods. RESULTS:
      Concordance rates in the genotype level between RFMP vs sequencing, sequencing vs
      HC, and HC vs RFMP were 98% (49/50), 88% (44/50), and 88% (44/50), respectivley.
      Especially, RFMP and sequencing were 100% concordant when assigned high-risk
      group was considered identical in 1 case of mixed genotypes identified only in
      RFMP. The observed discrepancy between HC and the other two methods is due to the
      assignment of six cases of low, intermediate, or unassigned risk genotypes as
      high-risk group in HC method. CONCLUSIONS: RFMP, sequencing, and HC assays were
      highly concordant with each other in HPV genotyping. Compared to sequencing
      assay, RFMP assay is found to be advantageous in detecting mixed genotype
      infections. The accuracy and amenability to high-throughput analysis should make
      the RFMP assay suitable for reliable screening of HPV genotypes in clinical
      laboratories.

PMID- 18094554
TI  - [Comparison of two new plastic tubes (Sekisui INSEPACK and Green Cross Green Vac
      Tube) with BD Vacutainer tubes for 49 analytes].
AB  - BACKGROUND: Becton Dickinson (BD) Vacutainer tubes are the most widely used
      vacuum system for collection of blood in clinical laboratories. We compared the
      performance of two new tubes, Sekisui INSEPACK tube and Green Cross Green Vac
      Tube, with the existing BD Vacutainer tubes for 49 common analytes. METHODS: A
      total of 20 apparently healthy volunteers were recruited for this study. For
      rountine chemistry and thyroid function tests, we compared the results of two new
      vacutainer tubes and BD Vacutainer tubes with those of BD glass tubes at t=0 hr
      by student paired t test. Hematology and coagulation test results of the two new
      vacutainer tubes were compared with those of BD Vacutainer tubes at t=0 hr. To
      study the stability of each analyte, results at t=24 +/- 2 hr, t=72 +/- 2 hr, and
      t=168 +/- 2 hr were compared with those at t=0 hr for each tube. RESULTS:
      Although paired t test analysis revealed statistically significant differences
      between two tested tubes and existing BD Vacutainer tube in several tests (total
      protein, total bilirubin, alkaline phosphatase, glucose, uric acid, calcium,
      inorganic phosphorus, direct bilirubin, triglyceride, HDL-cholesterol, LDL
      cholesterol, lactate dehydrogenase, triiodothyronine, and thyroxine), these
      differences were not considered clinically significant. Stability of two new
      vacuum tubes for each analyte was similar to that of the BD Vacutainer tube.
      CONCLUSIONS: Sekisui INSEPACK tube and Green Cross Green-Vac Tube showed a
      satisfactory analytical performance compared with existing BD Vacutainer tubes.
      We conclude that these two new plastic vacutainer tubes are acceptable for the
      commonly ordered laboratory tests.

PMID- 18094555
TI  - [JAK2(V617F) mutation in Korean patients with essential thrombocythemia].
AB  - BACKGROUND: Essential thrombocythemia (ET) is thought to reflect transformation
      of a multipotent hematopoietic stem cell, but its molecular pathogenesis remains
      obscure. But tyrosine kinase, especially Janus kinase 2 (JAK2), has been
      implicated in myeloproliferative disorders other than chronic myeloid leukemia.
      We investigated the frequency of JAK2 mutation and its correlation with other
      clinicopathologic variables in Korean patients with ET and reactive
      thrombocytosis (RT). METHODS: JAK2 mutation analysis was performed on genomic DNA
      from bone marrow aspirates of 24 patients with ET and peripheral blood in 36
      patients with RT using allele-specific PCR. RESULTS: JAK2 mutation was detected
      in 11 patients (46%) among the 24 patients with ET and was not found in 36
      patients with RT. In patients with ET, older age and leukocytosis were related
      with JAK2 mutation without statistical significance (P=0.172 and 0.094,
      respectively). But this mutation was not correlated with sex, hemoglobin,
      platelet count, splenomegaly, increased cellularity of bone marrow, bone marrow
      fibrosis and vascular complications. CONCLUSIONS: The current observation
      strengthens the specific association between JAK2 mutation and ET. At the
      diagnosis of ET in Korean patients, identification of JAK2 mutation should be
      incorporated in the basis for new approaches.

PMID- 18094556
TI  - [Clinical usefulness of plasma interleukin-6 and interleukin-10 in disseminated
      intravascular coagulation].
AB  - BACKGROUND: Disseminated intravascular coagulation (DIC) is a syndrome
      characterized by a systemic activation of coagulation leading to the
      intravascular deposition of fibrin and the simultaneous consumption of
      coagulation factors and platelets. Inflammatory cytokines can activate the
      coagulation system. This study investigated the diagnostic and prognostic
      usefulness of the plasma level of interleukin-6 (IL-6) and interleukin-10 (IL-10)
      for predicting DIC. METHODS: The study populations were 15 healthy controls and
      81 patients who were clinically suspected of having DIC and were requested to
      perform DIC battery tests. The presence of overt DIC was defined by the
      International Society on Thrombosis and Haemostasis Subcommittee cumulative score
      of 5 or above. The 28 day mortality was used to assess the prognostic outcome.
      The plasma levels of the cytokines were measured by ELISA. RESULTS: The plasma
      levels of IL-6 and IL-10 in patients (N=81) were higher than those of control
      (N=15). IL-6 and IL-10 levels of overt DIC group (N=31) were 3 times and 1.5
      times higher than those, respectively, of non-overt DIC group (N=50). In
      infection group (N=48), IL-6 and IL-10 levels of overt DIC group (N=18) were 5
      times and 3 times higher than those, respectively, of non-overt DIC group (N=30).
      The diagnostic efficiency of IL-6 (optimal cut off >40.4 pg/mL) and IL-10 (>9.7
      pg/mL) for the diagnosis of overt DIC were 67% and 69%, respectively, which were
      similar to that of D-dimer. Plasma levels of IL-6 and IL-10 were also higher in
      non-survivors than in survivors. The patients with higher levels of IL-6 and IL
      10 showed a poorer prognosis. CONCLUSIONS: The proinflammatory cytokine, IL-6 and
      anti-inflammatory cytokine, IL-10 were useful for the diagnosis of overt DIC and
      the prediction of its prognosis. These results also showed the evidence of a
      close interaction between coagulation and inflammation.

PMID- 18094557
TI  - Relationship between in vitro chemosensitivity assessed with MTT assay and
      clinical outcomes in 103 patients with acute leukemia.
AB  - BACKGROUND: Cellular drug resistance is supposed to play a major role in
      chemotherapy failure or relapse. The purpose of this study was to analyze the
      relationship between in vitro chemosensitivity test results using a 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and clinical
      response on chemotherapy, and to find the possibility of optimizing the treatment
      protocol for individual patients according to their actual drug resistance.
      METHODS: For MTT assay, we obtained bone marrow aspirates from 103 patients with
      acute leukemia at the time of initial diagnosis or relapse. The following drugs
      were tested: cytarabine, vincristine, methotrexate, daunorubicin, dexamethasone,
      L-asparaginase, and mitoxantrone. To evaluate clinical responses after induction
      chemotherapy, we followed up on their bone marrow study. RESULTS: In our study,
      in vitro chemosensitivity test with the MTT assay significantly predicted whether
      patients with AML remained continuous complete remission or went into relapse. It
      also predicted whether or not child patients with ALL would acquire complete
      remission after induction chemotherapy. CONCLUSIONS: Although it does not provide
      the insight into the mechanisms that cause drug resistance, the MTT assay may be
      a useful tool in individually optimizing the chemotherapy of patients with acute
      leukemia.

PMID- 18094558
TI  - [Laboratory evaluation of bone marrow metastasis: single institute study].
AB  - BACKGROUND: The incidence of bone marrow (BM) metastasis might be related with
      the occurrence of malignant tumors in ethnic groups. So, we investigated the type
      and the frequency of metastatic tumors of BM and analyzed the clinicopathologic
      variables of BM metastasis. METHODS: This study included 932 cases of primary
      malignant tumor which were requested for BM study from January 1995 to June 2006
      in Chonnam National University Hospital and Chonnam National University Hwasun
      Hospital. Peripheral blood smears (PBS); aspirates, touch prints, and trephine
      biopsies of BM; and medical records including other laboratory test results were
      reviewed. RESULTS: Overall frequency of BM metastasis was 11.9% (111/932).
      Primary tumors with BM involvement in children comprised neuroblastoma (74.1%),
      rhabdomyosarcoma (7.4%), and malignant lymphoma (7.4%). For adult patients, they
      consisted of malignant lymphoma (56.0%), gastrointestinal cancer (20.2%), and
      lung cancer (6.0%). In the case of malignant lymphoma, diffuse large cell
      lymphoma was the most frequent one. Laboratory findings of patients with BM
      metastasis commonly showed anemia and thrombocytopenia; in addition, serum LD,
      ALP, AST and ALT were elevated in 81.5% (75/92), 63.4% (59/93), 63.5% (61/96) and
      33.3% (32/96), respectively. Leukoerythroblastosis was observed only in 19.8%
      (22/111) on PBS examination. CONCLUSIONS: The most common non-hematopoietic
      metastatic tumor was neuroblastoma in children and gastrointestinal tumors in
      adults. Leukoerythroblastosis, anemia, and the elevation of serum LD, ALP, and
      AST were useful markers for the prediction of BM metastasis.

PMID- 18094559
TI  - A case of lineage switch from acute lymphoblastic leukemia to acute myeloid
      leukemia.
AB  - Lineage switch from acute lymphoblastic leukemia (ALL) to acute myeloid leukemia
      (AML) is very rare. We report a case of a 9 yr-old ALL patient relapsed as acute
      myelomonocytic leukemia. At the initial diagnosis, the blast cell morphology and
      immunophenotype were consistent with the diagnosis of typical ALL (L1 subtype
      according to FAB classification). The BCR-ABL fusion gene was not found by
      reverse transcription-PCR. Complete remission (CR) was achieved after induction
      and consolidation chemotherapy (Children's Cancer Study Group 1891 protocol,
      CCG1891). Nine months, which is a very short time compared with other cases in
      the literatures, after the diagnosis of ALL, she relapsed with completely
      different blasts (typical AML, M4 according to FAB classification) in morphology,
      cytochemistry, and immunophenotyping. The karyotype has changed from
      56,XY,+X,+Y,+Y,+4,+8,+10, +14,+17,-20,+21,+21,+21[6]/57,idem,+Y[19] to
      46,XY,t(8;16)(p11.2;p13.1)[19]/46,XY[1], showing unrelated chromosomal
      abnormality to the karyotype at the initial diagnosis. Moreover, both findings
      were quite specific for each common cell ALL and acute myelomonocytic leukemia.
      These findings support that this case is completely different leukemic clones
      occurred at each leukemic expression. The treatment with AML 2000 protocol
      chemotherapy failed, and he underwent the chemotherapy with the combination of
      high dose cytarabine and mitoxantrone and has been in CR state for 21 months,
      until now.

PMID- 18094560
TI  - [Evaluation of urine NMP22 point-of-care test for the screening of bladder
      cancer].
AB  - BACKGROUND: Screening of high-risk patients using bladder tumor markers can offer
      an advantage of early detection and saving medical costs. For these purpose many
      tumor markers have been developed to supplement invasive cystoscopy. Our study
      evaluated the NMP22 point-of-care test (NMP22 POCT), which is one of the tumor
      makers, comparing with the standard urine cytology for the diagnosis of bladder
      cancer. METHODS: From January to September 2005, 232 patients who had undergone a
      cystoscopy due to bladder cancer associated symptoms including hematuria and
      dysuria were enrolled in this study. Urine specimens were collected for NMP22
      POCT and cytology. NMP22 POCT and urine cytology were compared for sensitivity
      and specificity. In addition, we evaluated urine stick test and microscopy to
      explain some false-positive results in NMP22 POCT. RESULTS: Superficial
      transitional cell carcinoma was diagnosed in 10 patients. The sensitivity of
      NMP22 test was 60% (95% confidence interval [CI], 26.2-87.8%), whereas that of
      cytology was 33.3% (95% CI, 7.5-70.1%); however, the difference was not
      significant. The specificity of NMP22 test was 69.8% (95% CI, 63.3-75.8%),
      compared with 99.0% (95% CI, 96.5-99.9%) for cytology (P<0.001). The presence of
      microscopic RBCs in urine specimen was significantly associated with the lower
      specificity of NMP22 POCT (P=0.02). CONCLUSIONS: NMP22 POCT was significantly
      less specific than urine cytology. To be useful as a bladder cancer screening
      test, the NMP22 test should have a higher specificity.

PMID- 18094561
TI  - [In vitro antimicrobial synergy against imipenem-resistant Acinetobacter
      baumannii].
AB  - BACKGROUND: Most imipenem-resistant Acinetobacter baumannii (IRAB) isolates are
      multiresistant, leaving few options for an effective antimicrobial therapy. We
      purposed to select possible candidates for the combinations of antimicrobials
      that are synergistic in vitro for inhibitory or bactericidal activities against
      IRAB and evaluate the usefulness of double disk synergy test (DDS) in predicting
      synergistic bactericidal activity. METHODS: Fifty-five IRAB isolates recovered
      from patients during the period from August 1999 to November 2000 were tested for
      susceptibilities to amikacin, gentamicin, tobramycin, piperacillin,
      piperacillin/tazobactam, cefotaxime, cefepime, cefoperazone/sulbactam (C/S),
      imipenem, meropenem, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole,
      chloramphenicol, minocycline, and colistin by the Clinical and Laboratory
      Standard Institute agar dilution method. Three isolates showing different
      susceptibility profiles were tested for antimicrobial synergy by DDS and then by
      timekill study (TKS) using DDS-positive combinations. RESULTS: Colistin, C/S, and
      minocycline were active in 50 (90.9%), 50, and 44 (80.0%) isolates, respectively,
      and all the other drugs were active in less than 20% of isolates. Minocycline
      imipenem, minocycline-C/S, minocycline-amikacin, imipenem-tobramycin, C/S
      amikacin, and C/S-tobramycin combinations showed synergistic inhibitory or
      bactericidal activity by TKS when the same combinations were synergistic in DDS;
      however, C/S-imipenem was found synergistic on DDS, but not by TKS. CONCLUSIONS:
      Colistin, C/S, and minocycline were relatively active against IRAB. DDS might
      help predict the synergistic antimicrobial effect of TKS if one of the
      combinations was susceptible.

PMID- 18094562
TI  - [Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolates
      with toxic shock syndrome toxin and staphylococcal enterotoxin C genes].
AB  - BACKGROUND: Many methicillin-resistant Staphylococcus aureus (MRSA) isolates in
      Korea possess a specific profile of staphylococcal enterotoxins in that the toxic
      shock syndrome toxin gene (tst) coexists with the staphylococcal enterotoxin C
      gene (sec). Because the analysis of staphylococcal cassette chromosome mec
      (SCCmec), a mobile genetic element mecA gene encoding methicillin resistance,
      showed that majority of these are SCCmec type II, these MRSA isolates with tst
      and sec may be genetically related with each other. This study was performed to
      investigate the genetic relatedness of tstand sec-harboring MRSA strains isolated
      in Korea by using pulsed-field gel electrophoresis (PFGE). METHODS: A total of 59
      strains of MRSA isolates of SCCmec type II possessing tst and sec were selected
      for PFGE and phylogenetic analyses. These isolates were collected from 13 health
      care facilities during nationwide surveillance of antimicrobial resistance in
      2002. RESULTS: The 59 MRSA isolates were clustered into 11 PFGE types, including
      one major group of 26 strains (44.1%) isolated from 7 healthcare facilities.
      Seven PFGE types contained 2 or more isolates each, comprising 55 isolates in
      total. CONCLUSIONS: Most of SCCmec type II MRSA isolates containing tst and sec
      showed closely related PFGE patterns. Moreover, MRSA isolates collected from
      different healthcare facilities showed identical PFGE patterns. These findings
      suggested a clonal spread of MRSA strains possessing tst and sec in Korean
      hospitals.

PMID- 18094563
TI  - Isolation of Mycobacterium lentiflavum from a patient with a lung destroyed by
      tuberculosis.
AB  - Mycobacterium lentiflavum has recently been described as an emerging human
      pathogen without regard to the immune status of the host. We herein report on M.
      lentiflavum isolated from a respiratory specimen of a patient. Although the
      organism described in this case seems to be a colonizer of a lung destroyed by
      tuberculosis, the current methods for species identification of nontuberculous
      mycobacteria have to be re-evaluated so as not to underestimate these organisms.

PMID- 18094564
TI  - [Clinical significance of serum interleukin-18 concentration in the patients with
      atopic dermatitis].
AB  - BACKGROUND: Interleukin (IL)-18, a potent inducer of interferon gamma (IFN
      gamma), is known to have a role in diseases involving type-2 T helper cell
      responses including atopic dermatitis. In this study, we aimed to determine the
      clinical significance of serum IL-18 level in the patients with atopic
      dermatitis. METHODS: Serum concentration of IL-18, IFN-gamma, IgE, and blood
      eosinophil were measured in the patients with atopic dermatitis and healthy
      control subjects, and their association with the clinical score of the disease
      was analysed. RESULTS: Serum concentrations of IL-18 were significantly elevated
      in patients with atopic dermatitis compared to the healthy controls (332 pg/mL vs
      151 pg/mL, P<0.05). Serum levels of IL-18 (r=0.41, P=0.001), eosinophil (r=0.36,
      P=0.003), and IgE (r=0.32, P=0.009) correlated with clinical scores in the
      patients. Also, multiple regression analysis indicated that serum IL-18 and IgE
      levels were independent predictors for the clinical score of atopic dermatitis
      (r2=0.25, beta=0.39, P=0.001 and beta=0.32, P=0.009). CONCLUSIONS: Our results
      confirmed a significant correlation between the concentration of serum IL-18 and
      the severity of atopic dermatitis. Although serum IL-18 concentration reflects
      the disease severity, its usefulness as a clinical test needs to be further
      investigated, because its additive benefit over those of conventional blood tests
      is not evident so far.

PMID- 18094565
TI  - [Hematologic and clinical features of 3q21q26 syndrome: extremely poor prognosis
      and association with central diabetes insipidus].
AB  - BACKGROUND: 3q21q26 syndrome includes chromosomal abnormalities of
      inv(3)(q21q26), t(3;3) (q21;q26), and ins(3;3)(q26;q21q26). It causes
      hematological diseases by the leukemogenic mechanism that the enhancer of
      ribophorin I gene in 3q21 induces the transcription of ecotropic viral
      integration site-1 gene in 3q26. Recently, it has been proposed that the 3q21q26
      syndrome may be preceded by diabetes insipidus (DI), particularly when combined
      with monosomy 7, and is a unique disease entity. METHODS: From May 2001 to June
      2006, a total of 5 patients with hematologic malignancy were found to have
      3q21q26 syndrome and monosomy 7. Laboratory findings, clinical data, and
      association with DI were investigated. RESULTS: The rearrangement type of 3q21q26
      was inv(3)(q21q26) in four patients and t(3;3)(q21; q26) in one. These patients'
      French American British types were AML M1, M2, M4 and M7, showing evident
      dysmegakaryopoiesis. Aberrant antigenic expressions of CD7 and CD56 were
      observed. The platelet count was relatively high as AML. All the five patients
      were refractory or in early relapse. Patient 5 was diagnosed with AML M7 20 days
      after being diagnosed with DI. While DI was well controlled with oral
      desmopressin, leukemia was refractory to chemotherapy. CONCLUSIONS: This study
      supports the recent opinion that 3q21q26 syndrome with monosomy 7 combined with
      DI is a disease of unique characteristics. In the relation between DI and
      monosomy 7 or 3q21q26 syndrome, there has been no explanation about how acquired
      abnormality of hematopoietic cells affects production of DDAVP by neurohormonal
      cells in hypothalamus. The mechanism needs further study, and this research
      should contribute to the understanding of genetic roles in leukemia appearing in
      different forms.

PMID- 18094566
TI  - [A case of male infertility with a reciprocal translocation t(X;14)(p11.4;p12)].
AB  - A chromosomal abnormality was found in about 3.6-7.6% of males presenting with
      azoospermia or oligospermia. Translocations between X chromosome and autosomes
      are rarely seen genetic disorders that cause male infertility. We described here
      a 26-year-old infertile male with t(X;14)(p11.4; p12). He showed a normal
      phenotype without any familial history of congenital abnormalities. The
      cytogenetic analysis of the proband revealed an X-autosomal translocation,
      46,Y,t(X;14)(p11.4;p12), which was inherited from his mother. The testis biopsies
      indicated the arrest of spermatogenesis. There were no microdeletions of the
      azoospermia factor a (AZFa), AZFb and AZFc regions in the Y chromosome shown by
      PCR with 11 sequence-tagged site (STS) markers. According to the literature, male
      carriers of an X-autosome translocation are invariably sterile, regardless of the
      position of the break-point in the X chromosome. To our knowledge, this is the
      first case report of azoospermia with t(X;14)(p11.4;p12) in Korea.

PMID- 18094567
TI  - [Survey results of medical insurance reimbursement system for independent medical
      laboratories in Korea].
AB  - BACKGROUND: A questionnaire survey was performed to perceive the problem of the
      current medical insurance reimbursement system for laboratory tests referred to
      independent medical laboratories; then, we intended to find a way to improve the
      reimbursement system. METHODS: Questionnaires were distributed to 220 independent
      medical laboratories and 700 laboratory physicians from July through October
      2005. Frequency analysis was used to analyse the replies from 109 respondents to
      25 questionnaire items regarding the current medical insurance reimbursement
      system for referral tests, problems with the system, and suggestions for the
      improvement of the system. RESULTS: Among the 109 respondents to this survey, 49
      (45.8%) considered the current reimbursement system to be unsatisfactory, while
      only 16 (15.0%) answered satisfactory. The problem was that the referral clinics
      not the laboratories that performed the tests--would first receive their
      reimbursement for the laboratory tests from Health Insurance Review Agency (HIRA)
      and then give a portion of the laboratory test fees to the independent medical
      laboratories after the deduction of administrative fees. They (62.5% of the
      respondents) would prefer a separated reimbursement system by which the referral
      clinic-as well as the independent medical laboratory-would receive their
      reimbursement directly from HIRA through an Electronic Data Interchange (EDI)
      system. In this new system, 34% of the respondents expected the quality of the
      laboratory tests to be improved; however, 41.6% answered that the income of the
      referral clinic is expected to decrease. CONCLUSIONS: For the improvement of the
      medical insurance reimbursement system, the administrative fee for the referral
      clinic and the test fee for the independent medical laboratory should be
      reimbursed directly to the respective organizations. These changes could be made
      possible with the proper analysis of medical costs and the development of an
      effective EDI reimbursement system.

PMID- 18094568
TI  - [Standardization of terminology in laboratory medicine I].
AB  - BACKGROUND: Standardization of medical terminology is essential for data
      transmission between health-care institutions or clinical laboratories and for
      maximizing the benefits of information technology. Purpose of our study was to
      standardize the medical terms used in the clinical laboratory, such as test
      names, units, terms used in result descriptions, etc. During the first year of
      the study, we developed a standard database of concept names for laboratory
      terms, which covered the terms used in government health care centers, their
      branch offices, and primary health care units. METHODS: Laboratory terms were
      collected from the electronic data interchange (EDI) codes from National Health
      Insurance Corporation (NHIC), Logical Observation Identifier Names and Codes
      (LOINC) database, community health centers and their branch offices, and clinical
      laboratories of representative university medical centers. For standard
      expression, we referred to the English-Korean/ Korean-English medical dictionary
      of Korean Medical Association and the rules for foreign language translation.
      Programs for mapping between LOINC DB and EDI code and for translating English to
      Korean were developed. RESULTS: A Korean standard laboratory terminology database
      containing six axial concept names such as components, property, time aspect,
      system (specimen), scale type, and method type was established for 7,508 test
      observations. Short names and a mapping table for EDI codes and Unified Medical
      Language System (UMLS) were added. Synonym tables for concept names, words used
      in the database, and six axial terms were prepared to make it easier to find the
      standard terminology with common terms used in the field of laboratory medicine.
      CONCLUSIONS: Here we report for the first time a Korean standard laboratory
      terminology database for test names, result description terms, result units
      covering most laboratory tests in primary healthcare centers.

PMID- 18094569
TI  - [Investigation of hemostatic changes in patients with sepsis].
AB  - BACKGROUND: It is known that severe infection and inflammation lead to hemostatic
      abnormalities. Recently, much attention is focused on the mechanisms of infection
      or inflammation and on how it plays a central role in effecting the coagulation
      system. Disseminated intravascular coagulation in particular, is a common
      phenomenon in patients with sepsis, but the clinical implications of this
      condition are not clear. Therefore we attempted to evaluate the changes of the
      coagulation system in patients with sepsis and studied the factors that lead to
      such changes. METHODS: One hundred one patients diagnosed with sepsis were
      enrolled in this study. The patients were clinically evaluated for underlying
      disease and data for inflammatory status and coagulative changes were evaluated
      retrospectively. RESULTS: The WBC count increased in 76% and decreased in 6% of
      sepsis patients in comparison to the reference interval. The platelet count
      decreased in 65.3%. Changes in coagulative tests such as prothrombin time,
      activated partial thromboplastin time, antithrombin III, and D-dimer were
      observed in 70.4%, 52.7%, 87.2% and 100% of the patients, respectively.
      Correlation between ESR and fibrinogen was the highest in relation to the other
      coagulation factors. CRP also showed the highest correlation with fibrinogen in
      contrast to the other coagulation factors. CONCLUSIONS: This study confirmed the
      clear activation of coagulation in patients with sepsis. Of the evaluated factors
      involved in coagulation and fibrinolysis, fibrinogen showed the highest
      correlation to indices representing the inflammatory state. However further
      studies on the anticoagulant pathway are necessary in elucidating this matter.

PMID- 18094570
TI  - [Evaluation of the Abbott Cell-Dyn Sapphire hematology analyzer].
AB  - BACKGROUND: The performance of Cell-Dyn Sapphire (Abbott Diagnostic, USA) was
      compared to the Bayer Advia 2120 (Bayer Diagnostics, USA), Sysmex XE-2100 (Sysmex
      Corporation, Japan), and reference microscopy. METHODS: Three hundred samples for
      routine CBC and WBC differentials were randomly chosen for a comparison analysis.
      The Cell-Dyn Sapphire system was evaluated according to the linearity,
      imprecision, inter-instrument correlations, and white blood cell differential.
      RESULTS: The CBC parameters (WBC, RBC, hemoglobin and platelet) showed a
      significant linearity with correlation coefficients greater than 0.99 (P<0.0001).
      Coefficients of variation (CV) for within-run and differential count of WBC were
      less than 5% except for Total CV for monocytes, eosinophils, and basophils and
      within-run CV for low valued eosinophils. The correlation coefficients with
      manual count were lower in monocytes, eosinophils, and basophils than in
      neutrophils and lymphocytes. The correlation with other hematology anlayzers was
      significant exclusive of basophils. CONCLUSIONS: These results demonstrate that
      the Cell-Dyn Sapphire has a good linearity, an acceptable reproducibility, a
      minimal carryover, and a comparable performance with the sysmex XE-2100 and Advia
      2120.

PMID- 18094571
TI  - Investigation of von Willebrand factor gene mutations in Korean von Willebrand
      disease patients.
AB  - BACKGROUND: We intended to find the mutations of von Willebrand factor (VWF) gene
      as the most important contributing factor of von Willebrand disease (VWD) in
      Korean patients. METHODS: In 40 known vWD patients mutations of vWF gene were
      sought by direct sequencing of PCR products targeting exons 18, 19, 20, 26, 28
      and 52 frequently implicated as the locations of mutation. For factors other than
      VWF gene contributing to VWD phenotype, we tested ABO blood group and measured
      ADAMTS13 activity in VWD patients. RESULTS: Twenty-seven cases (67.5%) were type
      1 vWD, 3 cases (7.5%) type 3, and 5 cases (12.5%) type 2A. Three cases were type
      2A or 2B (7.5%) and 2 cases were suspected to be type 2N (5.0%). Among them six
      candidate missense mutations were found: V1279I, R1306W, R1308C, and V1316M were
      previously reported in type 2B and type 1 vWD, and C858W and T1477I were novel
      findings. All patients were heterozygotes. Blood group O was overly represented
      in VWD patients, while ADAMTS13 activity of the patients was not significantly
      different from that of normal control. CONCLUSIONS: Mutation of VWF gene detected
      by genetic studies can significantly improve the diagnostic accuracy, especially
      in subtype assignment of VWD. Two novel mutations, C858W and T1477I associated
      with VWD were found and expected to contribute to the elucidation of its
      pathophysiology.

PMID- 18094572
TI  - [Evaluation of CoaguChek XS for measuring prothrombin time in patients receiving
      long-term oral anticoagulant therapy].
AB  - BACKGROUND: Oral anticoagulation with warfarin requires routine monitoring of
      prothrombin time to maintain the international normalized ratio (INR) within the
      appropriate therapeutic range. Coagu- Chek XS (Roche Diagnositic, Germany) is a
      portable coagulometer that measures the INR. We evaluated the precision and
      accuracy of CoaguCheck XS by comparing it with CA-1500 (Sysmex, Japan). METHODS:
      We analyzed the CV and the correlation of all INR results measured in 68 samples
      obtained from patients treated with warfarin and 10 samples from control subjects
      with no history of anticoagulant therapy with CoaguChek XS and CA-1500. We
      compared the turn-around time between two instruments and evaluated the
      differences between the results obtained with venous and capillary blood samples
      and those obtained with different lots of the test strip. We also evaluated the
      precision of the two instruments in 5 repeated tests with samples of normal and
      increased INR. RESULTS: Mean INR values of 5 repeated tests with the same samples
      were similar. The correlation of INR values between two instruments was excellent
      (r2=0.97, P=0.001), and the difference in the values between the two instruments
      was mostly within the 95% limit of agreement, but was shown to increase in direct
      proportion to INR values. The turn-around time of CoaguChek XS was shorter than
      that of CA-1500. The differences between venous and capillary blood and between
      different lots of the test trip were not significant (P>0.05). CONCLUSIONS:
      CoaguChek XS showed a good precision and correlation with CA-1500 with a very
      short turn-around time. This instrument should be clinically useful in monitoring
      INR of patients with oral anticoagulation.

PMID- 18094573
TI  - [Bone marrow fibrin-ring granuloma: review of 24 cases].
AB  - BACKGROUND: Fibrin-ring granuloma (FRG), which can be found in bone marrow or the
      liver, is a subtype of epithelioid granuloma characterized by a central fat
      vacuole and annular peripheral fibrinoid materials. FRG has been proven to be
      associated with many etiologies such as several infectious organisms (Coxiella
      burnett; Epstein-Barr Virus, EBV; cytomegalovirus, CMV; and hepatitis A virus),
      allopurinol induced hepatitis, Hodgkin's lymphoma, and peripheral T-cell
      lymphoma. METHODS: We retrospectively reviewed 24 patients diagnosed with FRG by
      bone marrow biopsy at a single institute between 1995 and 2004. We reviewed
      clinical symptoms and laboratory findings of the patients, classified them by
      etiology, and compared prognosis of each group. RESULTS: The most common cause of
      FRG was acute or chronic EBV infection. Chronic or acute EBV infection was
      associated with 41.4% of patients (10/24). Of the remaining patients, 33.3%
      (8/24) were leukemia or lymphoma patients after chemotherapy, 4.2% (1/24) was a
      patient with hepatic failure, and 20.8% (5/24) were diagnosed as fever of unknown
      origin. The most common symptom and clinical finding were fever and cytopenia.
      EBV-associated group comprised chronic active EBV infection, EBV-associated
      hemophagocytic histiocytosis, acute EBV infection, EBV-associated
      lymphoproliferative disease, and Langerhans' cell histiocytosis. The EBV
      associated group showed a lower survival probability compared with the non-EBV
      group (P<0.05). CONCLUSIONS: Patients with bone marrow fibrin ring granuloma
      accompanied by fever require an active workup to find out the cause of infectious
      agents including EBV infection particularly due to their poor prognosis.

PMID- 18094574
TI  - [Acute hemolysis and renal failure caused by hepatitis A infection with
      underlying glucose-6-phosphate dehydrogenase deficiency].
AB  - Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common
      enzyme disorder worldwide, it has rarely been reported among Korean. The patient
      was previously healthy 39 yr old male who showed severe hemolytic anemia and
      acute renal failure accompanied by hyperbilirubinemia after hepatitis A
      infection. The additional studies for differential diagnosis of hemolytic anemia
      showed a moderate deficiency of G6PD enzyme. Because hepatitis A infection in
      patient with G6PD deficiency present much more severe clinical symptoms, G6PD
      enzyme should be examined in patients with triggering factors of hemolysis such
      as hepatitis A infection.

PMID- 18094575
TI  - [Evaluation of SD BIOLINE tetanus kit].
AB  - BACKGROUND: Point-of-care-testing (POCT) kits for tetanus toxoid antibody are
      used in emergency departments to evaluate the immunization status of patients
      with tetanus. The objective of this study was to evaluate the analytical
      performance and the utility of SD BIOLINE tetanus kit (Standard Diagnostic Inc.,
      Yongin, Korea), as a POCT. METHODS: A total of 326 peripheral blood specimens
      (whole blood, 319; serum, 326) from healthy subjects and patients were used. SD
      BIOLINE tetanus kit was evaluated for precision, accuracy, effect of specimens,
      operator variance, and the total processing time. The results from SD BIOLINE
      tetanus kit were compared with those from 2 quantitative ELISA kits. RESULTS:
      Compared with ELISA kits, SD BIOLINE tetanus kit revealed a sensitivity of 88
      97%, specificity of 87-92%, positive predictive value of 81-89%, negative
      predictive value of 90-98%, and kappa agreement of 0.78-0.82. SD BIOLINE tetanus
      kit also showed an excellent precision and a high accuracy. It showed a high
      concordance rate between whole blood and serum specimens. The total processing
      time of SD BIOLINE tetanus kit was 30-40 min. CONCLUSIONS: SD BIOLINE tetanus kit
      showed an excellent analytical performance. With its rapid turnaround time and
      the ease of handling and interpretation, SD BIOLINE tetanus kit seems appropriate
      for the evaluation of tetanus immunization status as a POCT device. However,
      education for operators and standardized guidelines for result interpretation
      should be emphasized.

PMID- 18094576
TI  - Inflammatory marker expression and its implication in Korean ischemic stroke
      patients.
AB  - BACKGROUND: Ischemic stroke is a complex condition influenced by many factors.
      Previous studies have demonstrated that inflammatory markers might play a role in
      such vascular diseases. Therefore the purpose of this study was to compare the
      expression of inflammatory markers in Korean ischemic stroke patients and to
      investigate their relationship to APOE polymorphism. METHODS: The patient group
      consisted of 275 patients with large artery atherosclerosis (LAA, n=169) and
      small artery occlusion (SAO, n=106). One hundred and nineteen age matched healthy
      subjects were recruited as the control group. Serum levels of three inflammatory
      markers (matrix metalloproteinase, MMP-9; tissue inhibitor of metalloproteinase
      1, TIMP-1; and high-sensitivity C-reactive protein, hs-CRP) were measured in each
      patient by using commercially available kits. Comparison of clinical risk
      factors, inflammatory marker levels, and APOE genotypes between the stroke
      patient group and control group and between the two patient subgroups was
      assessed. RESULTS: Comparison of the stroke group to control group showed
      significantly elevated levels of circulating MMP-9 (P<0.01) and hs-CRP (P=0.01).
      Comparison between the individual subgroups revealed a significantly higher level
      of only TIMP-1 in the LAA subgroup compared to the SAO subgroup (P<0.01). There
      was no significant difference in inflammatory marker levels among each allele
      carrier. CONCLUSIONS: The present study revealed the obvious tendency of
      increased circulating inflammatory markers in the patients with acute ischemic
      attack, especially MMP-9 and hs-CRP. Our observations suggest that measurement of
      serum MMP-9, TIMP-1, and hs-CRP levels may be useful in the diagnosis of ischemic
      stroke patients.

PMID- 18094577
TI  - [Pseudo-outbreak of Stenotrophomonas maltophilia due to contamination of
      bronchoscope].
AB  - BACKGROUND: We noticed an abrupt increase in the isolation of Stenotrophomonas
      maltophilia from bronchoalveolar lavage (BAL) specimens collected at Chosun
      University Hospital. We performed surveillance cultures in order to identify the
      source of what appeared to be a pseudo-outbreak. METHODS: To investigate a
      possible nosocomial outbreak of S. maltophilia, we performed culture of 11
      environmental specimens obtained from a bronchoscopy room and two bronchoscopes.
      Pulsed-field gel electrophoresis (PFGE) was used to examine the genetic
      relatedness among the strains of S. maltophilia recovered from BAL specimens of 3
      patients and 1 environmental sample, as well as 9 unrelated strains of S.
      maltophilia as a control. RESULTS: During a 7 day-period in March 2006, S.
      maltophilia was isolated from the BAL specimens of 7 of 13 (54%) patients,
      compared to only 5 of 188 (2.6%) patients during the 6-month period prior to that
      period. S. maltophilia was isolated from 1 of the 11 environmental samples, which
      was obtained from a fiberoptic bronchoscope suction channel. All 7 patient
      isolates and one environmental isolate exhibited similar antibiotic
      susceptibility patterns. PFGE analysis of the genomic DNA from epidemic strains
      demonstrated an identical banding pattern, whereas each of epidemiologically
      unrelated strains showed a unique electrophoretic pattern. CONCLUSIONS:
      Apparently one of the hospital bronchoscopes became contaminated with S.
      maltophilia during a bronchoscopic procedure. It is likely that subsequent
      specimen contamination occurred because the bronchoscope had been inadequately
      cleaned and disinfected. The pseudo-outbreak was controlled successfully by
      removing the source of infection.

PMID- 18094578
TI  - [Evaluation of the OC-SENSOR neo system for testing fecal occult blood].
AB  - BACKGROUND: Fecal occult blood tests (FOBTs) have been widely used as a means of
      colorectal cancer screening. Automated FOBTs using immunologic principles have
      the advantages such as quantitation, high specificity, and high throughput. We
      evaluated a newly-introduced automated FOBT analyzer, OC-SENSOR neo (OC neo)
      (Eiken Chemical Co., Japan). METHODS: The precision, linearity, and carry-over
      rate of OC neo were assessed with specimens prepared in accordance with the
      guidelines of CLSI. We performed a parallel test between OC neo and OC-SENSOR I
      (OC I) (Eiken Chemical Co.) using 300 consecutive stool specimens and 60 OC I
      positive specimens. The results were analyzed with SPSS version 13.0 (SPSS Inc.,
      USA). RESULTS: The coefficients of variation (CV) of within-run, between-run, and
      between-day using OCControl L (Eiken Chemical Co.) of ca. 150 ng/mL were 3.5
      7.8%, 4.5-8.8% and 4.9-5.0%, respectively. The linear regression coefficient and
      carry-over rate with the range of 67.8-939.4 ng/mL were 0.9998 (P<0.001), and
      0.1%, respectively. Correlation coefficient between OC neo and OC I was R2=0.954
      (P<0.001) for 60 OC I-positive specimens. The positive and negative
      interpretations of 300 consecutive specimens by OC neo were completely consistent
      with those of OC I. CONCLUSIONS: Because OC neo showed an excellent performance
      and a good correlation with OC I, OC neo warrants to be a reliable quantitative
      FOBT system for high volume laboratories.

PMID- 18094579
TI  - [Emergence of beta-lactam-dependent Bacillus cereus associated with prolonged
      treatment with cefepime in a neutropenic patient].
AB  - Antibiotic dependence in clinical isolates has been reported, albeit rarely, such
      as vancomycin-dependent enterococcus and beta-lactam-dependent Staphylococcus
      saprophyticus. We report herein a clinical isolate of beta-lactam-dependent
      Bacillus cereus. A 16-yr-old female was admitted on 8 September 2005 with
      neutropenic fever during chemotherapy following surgical removal of peripheral
      neuroectodermal tumor. She had had an indwelling chemoport since August 2004 and
      experienced B. cereus bacteremia three times during the recent 3-month period
      prior to the admission; the bacteremias were treated with cefepime-based
      chemotherapy. On hospital days 1 and 3, B. cereus was isolated from blood drawn
      through the chemoport. The isolates were resistant to penicillin, ceftriaxone,
      and erythromycin, and susceptible to vancomycin and ciprofloxacin. The isolate of
      hospital day 3 grew only nearby the beta-lactam disks including penicillin and
      ceftriaxone on disk diffusion testing. The beta-lactam-dependent isolate required
      a minimum of 0.064 microg/mL of penicillin or 0.023 microgram/mL of cefotaxime
      for growth, which was demonstrated by E test (AB Biodisk, Sweden). Light
      microscopy and transmission electron microscopy revealed a marked elongation of
      the dependent strain compared with the non-dependent strain. Prolonged therapy
      with beta-lactams in the patient with an indwelling intravenous catheter seemed
      to be a risk factor for the emergence of beta-lactam-dependence in B. cereus.

PMID- 18094580
TI  - [Comparative analysis of bronchoalveolar lavages in interstitial lung diseases].
AB  - BACKGROUND: This study was purposed to find out the differences in the lymphocyte
      subsets and differential cell counts of the bronchoalveolar lavage (BAL) fluid in
      patients with interstitial lung disease (ILD) and to analyze the differences
      according to their ages, gender and smoking habits. METHODS: BAL fluid samples of
      141 ILD patients were examined for lymphocyte subsets and differential cell
      counts, and the differences among the patients were analyzed according to their
      diseases. Then, within the three most common disease groups, the differences were
      further analyzed by the age, gender and smoking habit of the patients. RESULTS:
      There were no statistically significant differences in total cell counts (per
      millimeters of BAL fluid) among the patient groups with each ILD. However,
      significant differences were observed in the percentages of neutrophils,
      lymphocytes, eosinophils, and macrophages of BAL fluid. Also, in lymphocyte
      subset analyses, the percentages of total T cells, B cells, CD4+ T cells, CD8+ T
      cells, CD4/CD8 T cell ratios, and NK cells were significantly different among the
      patients with each ILD. However, within the same disease group, there were no
      differences in differential cell counts and lymphocyte subset analyses according
      to the age, smoking habit, and gender of the patients. CONCLUSIONS: Although the
      age, smoking habit and gender did not have an effect on the BAL fluid analyses
      among the patients with the same ILD, there were significant differences among
      the patients with each ILD; therefore, the differential cell counts and
      lymphocyte subset analyses of BAL fluid can be useful in differential diagnosis
      for determining the types of ILD.

PMID- 18094581
TI  - [Treatment outcome of multidrug resistance related mRNA expression and c-jun-N
      terminal kinase activity in patients with acute myeloid leukemia].
AB  - BACKGROUND: The multidrug resistance (mdr1), multidrug resistance associated
      protein (mrp1), and glutathione-s-transferase (gst) pi genes have been associated
      with treatment failure in acute myeloid leukemia (AML). c-jun N-terminal kinase
      (JNK) activity is increased in response to chemotherapeutic agent. METHODS: To
      investigate the significance of multidrug resistance (mdr) parameters and JNK
      activity, bone marrow or peripheral blood cells from 52 patients with AML were
      analyzed. RT-PCR was performed for mdr1, mrp1, and gst pi gene expression. JNK
      expression and activity were measured using an immunoe- nzymatic kinase assay and
      a western blot method. RESULTS: High level expression of mdr1, mrp1, and gst pi
      mRNA was observed in 38.5%, 48.1% and 54.3% of AML cases, respectively. The
      remission rate was significantly low in cases with an older age (>55 yr), a high
      WBC count, poor chromosomal abnormalities, a high level expression of mdr1 and
      mrp1. The WBC count and mdr1 mRNA expression were independent predictors for the
      outcome to induction chemotherapy. There was a shorter duration of overall
      survival in the patients with an older age, a high WBC count, chromosome
      aberrations, high level expressions of mdr1 and mrp1 mRNA, and JNK activation.
      The patient's age, WBC count and chromosomal abnormalities were independent
      predictors for overall survivals. The majority (28/30) of AML cases did not show
      any levels of JNK activation except for two cases, which were associated with an
      extremely high WBC count, chromosomal aberration, high level expressions of mdr1,
      mrp1 and gst pi mRNA, and treatment resistance. CONCLUSIONS: These data indicate
      the influences of mdr1 and mrp1 mRNA expression on the clinical outcome of AML to
      induction chemotherapy. But it will be necessary to investigate further whether
      blast cells of AML resistant to chemotherapy retain the capacity to activate JNK,
      and relate to MDR parameters.

PMID- 18094582
TI  - [Prevalence of FLT3 internal tandem duplication in adult acute myelogenous
      leukemia].
AB  - BACKGROUND: fms-like tyrosine kinase (FLT3), a member of the class III receptor
      tyrosine kinases, regulates the proliferation and differentiation of
      hematopoietic stem cells. An internal tandem duplication of the FLT3 gene
      (FLT3/ITD) has been reported in acute myelogenous leukemia (AML) and may be
      associated with a poor prognosis. In this study we determined the prevalence and
      prognostic significance of FLT3/ITD in adult AML patients. METHODS: This study
      included 52 adult de novo AML. Exon 14 and 15 of the FLT3 gene were amplified by
      PCR and the PCR products were analyzed by 3730XL DNA analyzer (Applied
      Biosystems, USA) and GeneMapper Software. RESULTS: FLT3/ITD was found in 15
      (28.8%) of the 52 AML patients. The presence of FLT3/ITD was significantly
      associated with absolute leukocyte counts (P=0.002) and bone marrow blast counts
      (P=0.036). FLT3/ITD was also more frequent in patients with normal karyotype (7
      of 18) than in those with cytogenetic aberrations (3 of 25). Patients with t
      (15;17) showed a higher prevalence of FLT3/ITD (2 of 7). FLT3/ITD was
      significantly associated with overall survival (P<0.042). CONCLUSIONS: Our data
      indicate that FLT3/ITD is a common alteration in adult AML patients. Although
      based on a study with a limited number of AML patients, FLT3/ITD is a prognostic
      marker in patients with AML.

PMID- 18094583
TI  - [A case of therapy-related acute monocytic leukemia following low-dose of
      etoposide treatment for hemophagocytic lymphohistiocytosis].
AB  - We report a case of therapy-related acute myeloid leukemia after low-dosed
      topoisomerase II inhibitor (etoposide) treatment for hemophagocytic
      lymphohistiocytosis (HLH). A 62-yr-old female patient had previously been treated
      with a HLH-94 protocol containing a low-dose of etoposide (total dose of 300
      mg/m2). Thirty-one months later, the patient was admitted to the hematology
      department with general weakness and upper respiratory infection symptoms.
      Peripheral blood smear and bone marrow study revealed acute monocytic leukemia.
      There was no evidence of myelodysplastic syndrome, and a cytogenetic study showed
      no chromosomal abnormalities.

PMID- 18094584
TI  - [A case of IgA kappa light chain deposition disease and combined adult Fanconi
      syndrome with auer rod-like intracytoplasmic inclusions in plasma cells and
      proximal renal tubular cells].
AB  - We report a case of IgA kappa light chain deposition disease and combined adult
      Fanconi syndrome with Auer rod-like intracytoplasmic inclusions in plasma cells
      and proximal renal tubular cells in a 54-yr-old female. Cytochemical stainings
      revealed a strong acid phosphatase activity of the inclusions and weak periodic
      acid-Schiff positivity, whereas the reactions for peroxidase and alpha-naphthyl
      acetate esterase were negative. An immunostaining verified IgA-kappa inside the
      plasma cells. Kidney biopsy revealed Bence Jones cast nephropathy with kappa
      light chain positivity, and Congo red staining was negative. Electron microscopy
      showed needle-shaped crystals located in tubular epithelial cells.

PMID- 18094585
TI  - A case of CD45-, CD19- precursor B cell acute lymphoblastic leukemia with an
      atypical morphology.
AB  - The differential diagnosis of acute lymphoblastic leukemia (ALL) from other small
      round blue cell tumors in children is very important for proper treatment, but
      sometimes difficult. CD45 is expressed on almost all-human leukocytes and not
      expressed on other small round blue cell tumors. Moreover, CD19 is expressed on
      all stages of B lineage cells and loss of this antigen is very rare in precursor
      B-cell ALL. We report a case of ALL with atypical morphology and immunophenotype.
      A 6-yr-old girl presented with fever and weight loss. Many abnormal cells with
      variable sized, high nuclearcytoplasmic ratio and distinct nucleoli were counted
      23% in bone marrow. The results of immunophenotyping were negative for CD45,
      CD19, CD10, CD20, CD3, CD5, CD7, CD56/16, CD13, and CD33 and positive for CD22,
      TdT, and CD34. The immunohistochemical staining of bone marrow biopsies was
      positive for CD79a, CD10, TdT and CD99. The cytogenetic study showed normal
      karyotype but amplification of MLL (myeloid/lymphoid or mixed lineage leukemia)
      gene was suggestive in the fluorescent in situ hybridization. The patient
      received the standard chemotherapy for acute lymphoblastic leukemia and reached
      complete remission.

PMID- 18094586
TI  - [Distribution of TT virus genotypes and genogroups in 69 healthy and 59 hepatitis
      B virus infected Korean individuals].
AB  - BACKGROUND: TT virus (TTV) infection is highly prevalent in general population
      and patients with hepatitis B virus (HBV) infection. The aim of the present study
      was to determine the distribution of the genotypes and genogroups of TTV in
      healthy and HBV-infected individuals in Korea. METHODS: Distribution of TTV
      genotypes and genogroups was investigated in the serum samples of 69 healthy and
      59 HBV-infected individuals. PCR products of N22 region were genotyped by
      sequence analysis. TTV genogroups were determined by 5 different genogroup
      specific PCR assays. RESULTS: Among the 20 sequenced isolates, 9 (45%) were
      genotype 2, 8 (40%) were genotype 1, 2 (10%) were genotype 3, and 1 (5%) was
      genotype 4. TTV genogroup 4 was found most frequently (52/128), followed by
      genogroup 3 (42/128), genogroup 1 (35/128), genogroup 5 (32/128), and genogroup 2
      (1/128). Mixed infections with different genogroups were frequent. CONCLUSIONS:
      TTV genotype 2 and 1 are predominant genotypes. TTV genotype 3 was detected for
      the first time in Korea. TTV genogroups 4 and 3 were predominant genogroups. No
      significant difference was observed in the distribution of TTV genogroups between
      healthy and HBV-infected individuals.

PMID- 18094587
TI  - [Microorganisms isolated from blood cultures and their antimicrobial
      susceptibility patterns at a university hospital during 1994-2003].
AB  - BACKGROUND: Blood culture is important for the determination of the etiologic
      agent of bacteremia. Analysis of blood culture results and antimicrobial
      susceptibility trend can provide clinicians with relevant information for the
      empirical treatment of patients. METHODS: The species and antimicrobial
      susceptibility of the isolates from blood cultures at the Severance Hospital
      during 1994-2003 were analysed. Blood specimens were cultured for 7 days using
      tryptic soy broth and thioglycollate medium. Identification of organism was based
      on conventional methods or commercial kit systems. Antimicrobial susceptibility
      was tested by a disk diffusion method. RESULTS: Of 536,916 blood specimens
      cultured, 24,877 (4.6%) from 13,102 patients were positive. Among the isolates,
      93.1% were aerobic or facultative anaerobic bacteria, 3.3% anaerobes, and 3.6%
      fungi. Escherichia coli was isolated most frequently, followed by Staphylococcus
      aureus, alpha-hemolytic Streptococcus, Enterococcus spp., and Klebsiella
      pneumoniae. The proportion of patients with Enterococcus faecium and K.
      pneumoniae gradually increased during this study. Enterococcus, S. aureus and
      alpha-hemolytic Streptococcus were frequently isolated from the age group of less
      than 2 yr. E. coli, Enterococcus spp., K. pneumoniae and S. aureus from the age
      group of over 50 yr. Oxacillin-resistant S. aureus decreased, whereas vancomycin
      resistant E. faecium and imipenemresistant Pseudomonas aeruginosa and
      Acinetobacter baumannii increased. CONCLUSIONS: E. coli was the most common cause
      of bacteremia and S. aureus, alpha-hemolytic Streptococcus, and K. pneumoniae
      were frequently isolated pathogens. The bacteremia due to Enterococcus, K.
      pneumoniae, fungi, vancomycin-resistant E. faecium, and imipenem-resistant P.
      aeruginosa and A. baumannii gradually increased during this period.

PMID- 18094588
TI  - [Detection of mecA in strains with oxacillin and cefoxitin disk tests for
      detection of methicillin-resistant Staphylococcus].
AB  - BACKGROUND: Cinical and Laboratory Standards Institute (CLSI) recommends the use
      of cefoxitin disks instead of long-used oxacillin disks for screening methicillin
      resistant isolates of staphylococci. The frequency of discrepant results and
      accuracy of the tests were evaluated by detecting mecA gene. METHODS: A total of
      3,123 Stapylococci isolates from patients in Severance Hospital were tested
      during September 2005 to August 2006 by the CLSI-recommended test using both
      cefoxitin and oxacillin disks. The mecA gene was detected by PCR and the
      oxacillin minimum inhibitory concentration (MIC) was determined by using agar
      dilution method for the isolates with discrepant tests. RESULTS: Among 1,915 S.
      aureus islolates tested, one isolate was resistant to oxacillin disk but
      susceptible to cefoxitin disk; the isolate did not have mecA gene. Another
      isolate susceptible to oxacillin but resistant to cefoxitin had mecA gene. Among
      1,208 coagulase-negative staphylococcal isolates, 15 isolates were resistant to
      oxacillin disk but susceptible to cefoxitin disk; the isolates did not have mecA
      genes. Two isolates susceptible to oxacillin disk but resistant to cefoxitin disk
      had mecA genes. Among the 16 Staphylococcus isolates that did not have mecA gene,
      15 isolates had the oxacillin MICs of </= 2 microg/mL and were considered as
      methicillin-susceptible, while 1 isolate with the MIC of 4 microg/mL was
      considered as methicillin-resistant. CONCLUSIONS: Overall, 1.9% of staphylococcal
      isolates showed discrepant results when the screening tests were performed by
      using oxacillin and cefoxitin disks. None of the isolates resistant to oxacillin
      disk but susceptible to cefoxitin disk had mecA gene. In conclusion, the
      cefoxitin disk test is more reliable than oxacillin disk test in screening
      methicillin-resistant staphylococcal isolates.

PMID- 18094589
TI  - [Usefulness of bile cultures and predictive factors for bacteriobilia in
      percutaneous cholecystostomy in patients with acute cholecystitis].
AB  - BACKGROUND: Bile cultures have been used to diagnose and predict the prognosis of
      acute cholecystitis (AC). As the standard treatment for AC has changed, the
      appropriate timing and clinical usefulness of bile cultures should be
      reevaluated. We analyzed the incidence of positive bile cultures in
      cholecystostomy and cholecystectomy, and attempted to see if a positive bile
      culture is related to the laboratory and imaging parameters and postoperative
      infections. METHODS: Included in the study were 86 patients with AC who underwent
      percutaneous cholecystostomy (PC) and then laparoscopic cholecystectomy (LC). We
      performed hematologic, biochemical, and radiological analyses at admission and
      bile cultures with each surgical procedure. The patients were followed for two
      months for postoperative infections. RESULTS: Bile cultures were positive in
      40.7% of the patients at PC, significantly higher than at LC (12.8%). The group
      with positive cultures showed a higher median age and elevated levels of alkaline
      phosphatase (ALP) and total bilirubin (TB) than the group with negative cultures.
      Univariate analysis identified three preoperative factors as predictors of
      positive bile cultures: age (>55 yr), ALP (>100 IU/L) and TB (>1.2 mg/dL).
      Infectious complications after LC were mild and the incidence of postoperative
      infections was not different between the groups. CONCLUSIONS: The sensitivity of
      bile cultures is low for diagnosing AC, and the adequate timing of bile cultures
      is at PC, rather than LC. An old age and factors (ALP & TB) manifesting an
      advanced stage of bile stasis are associated with positive bile cultures. No
      correlation was found between positive bile cultures and postoperative
      infections.

PMID- 18094590
TI  - [Panton-Valentine leukocidin positive Staphylococcus aureus isolated from blood
      in Korea].
AB  - BACKGROUND: Panton-Valentine leukocidin (PVL) is a pore-forming toxin secreted by
      some Staphylococcus aureus strains and associated with skin and soft tissue
      infections; these strains are epidemiologically associated with current outbreaks
      of community-acquired methicillin-resistant S. aureus (MRSA) and with necrotizing
      pneumonia in healthy adults in USA and Europe. This study was performed to
      investigate the presence of PVL-positive S. aureus and the significant infections
      known to be caused by this organism. METHODS: A total of 573 strains of S. aureus
      blood isolates at university-affiliated hospital during 2002 to 2005 were
      selected. The presence of PVL was investigated using PCR. Additional 12
      staphylococcal toxin genes were also examined in PVL-positive S. aureus strains,
      and MRSA isolates were typed for the staphylococcal cassette chromosome mec
      (SCCmec). RESULTS: PVL genes were detected in 5 (0.9%) of 573 S. aureus strains,
      including 1 MRSA and 4 MSSA. The PVL-positive MRSA isolate was SCCmec type IV,
      and no other staphylococcal toxins were detected. The median age of the patients
      infected with PVL-positive S. aureus was 36 yr. Three cases of bacteremia were
      preceded by skin and soft-tissue infections. CONCLUSIONS: Bacteremia caused by
      PVL-positive S. aureus strain were detected in 5 patients in Korea, and some of
      the patients were associated with severe skin and soft-tissue infections. In
      addition, the PVL-positive MRSA strain of SCCmec type IV, a characteristic of
      community-acquired MRSA isolates in USA and Europe, also exists in Korea, and can
      cause the severe infections known to be associated with this organism.

PMID- 18094591
TI  - [In vitro activity of arbekacin against clinical isolates of Staphylococcus
      species and gram-negative bacilli].
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and some gram
      negative bacilli are very prevalent nosocomial pathogens, commonly causing mixed
      infections, and are often resistant to multiple drugs. Arbekacin is an
      aminoglycoside used for the treatment of MRSA infections, but is also active
      against some gram-negative bacilli. The aim of this study was to determine in
      vitro activity of arbekacin against recent clinical isolates of staphylococci and
      gram-negative bacilli. MATERIALS AND METHODS: The strains were isolated from
      clinical specimens of patients at Severance Hospital in 2003. Antimicrobial
      susceptibility was tested by the Clinical and Laboratory Standards Institute agar
      dilution method. The following arbekacin breakpoints were used: susceptible, </=4
      microg/mL; and resistant, >/=16 microg/mL . RESULTS: All isolates of
      staphylococci tested were inhibited by </=4 microg/mL of arbekacin, regardless of
      their methicillin susceptibility. The MIC90s of arbekacin, 1-4 microg/mL, were 8
      >32-fold and >32-128-fold lower than those of amikacin and gentamicin,
      respectively. The resistance rates of MRSA, methicillin-susceptible S. aureus,
      methicillin-resistant coagulase-negative staphylococci (CNS) and methicillin
      susceptible CNS were 0% to arbekacin, 0-54% to amikacin, and 24-79% to
      gentamicin. The MIC90s of arbekacin for Escherichia coli and Citrobacter
      freundii, 1 microg/mL and 16 microg/mL, were 2-4-fold and 8-16-fold lower than
      those of amikacin and gentamicin, respectively. However, The MIC90s of arbekacin
      for other species of gram-negative bacilli, 64->128 microg/mL, were similar to
      those of other aminoglycosides. CONCLUSIONS: Arbekacin may be a useful
      alternative to glycopeptides for the treatment of monomicrobial methicillin
      resistant staphylococcal infections, as well as mixed infections with gram
      negative bacilli, as most isolates of E. coli, C. freundii and some other gram
      negative bacilli were also susceptible to arbekacin.

PMID- 18094592
TI  - [Evaluation of Biosewoom Real-Q Cytomegalovirus Quantification kit for
      Cytomegalovirus viral load measure].
AB  - BACKGROUND: Rapid and accurate laboratory tests are essential to detect
      cytomegalovirus (CMV) infections in solid organs and haematopoietic stem cell
      transplant recipients. We assessed the realtime quantitative PCR (RQ-PCR)
      technology for its usefulness in detecting CMV DNA. METHODS: We evaluated the
      analytical performance of CMV RQ-PCR using Real-Q Cytomegalovirus Quantification
      kit (BioSewoom Inc., Korea). To evaluate its clinical utility, we also compared
      it to pp65 antigenemia test, an immunostaining method, on 343 samples of total 84
      patients, including 63 transplant recipients. RESULTS: The detection limit of RQ
      PCR was 63 copies/mL and none of hepatitis B virus, hepatitis C virus, or human
      immunodeficiency virus showed a cross-reactivity with CMV. Total coefficient of
      variation (CV) was 10.4-19.5%. It detected CMV DNA in a linear range from 1 x
      10(2) to 5 x 10(11) copies/mL (P<10(-13), R(2)=0.9994). The qualitative positive
      rates of pp65 antigenemia test and RQ-PCR were 4.7%, 16.3%, respectively and
      concordance rate between the two tests was 84.8% (Kappa=0.221, P<10(-6)). In
      comparison of quantitative results, the correlation between two tests was
      significant (r=0.45, P<10(-17)). In comparison among three groups by pp65 antigen
      level, CMV DNA level obtained with RQ-PCR increased significantly (P<10(-3) and
      P<10(-7), respectively). CONCLUSIONS: The RQ-PCR is easier to perform than the
      immunostaining method, has good analytical performance and reflects the blood
      level of viral DNA well. It may be a new method substituting the pp65 antigenemia
      test. Further studies determining RQ-PCR value starting pre-emptive therapy will
      be required.

PMID- 18094593
TI  - [Clinical significance of quantitation of WT1 gene expression for minimal
      residual disease monitoring of acute myelogenous leukemia].
AB  - BACKGROUND: Following induction chemotherapy for AML, a sensitive determination
      of minimal residual disease (MRD) in patients achieving complete remission (CR)
      should enable the detection of early relapse. This study was designed to verify
      if quantitative assessment of the Wilms' tumor (WT1) gene by real time polymerase
      chain reaction (RQ-PCR) can be used as a marker for MRD detection during the
      monitoring of AML. METHODS: WT1 gene expression was quantified by RQ-PCR in 31
      patients with AML at diagnosis (27 patients) and during follow-up (29 patients)
      relative to ABL control gene. In four patients, the WT1 gene expression was
      analyzed in comparison to a second PCR marker, PML-RARA fusion transcript.
      Prognostic significance of WT1 gene expression was analyzed at diagnosis and at
      the primary CR evaluation. Longitudinal WT1 gene analysis was performed in 17 AML
      patients. RESULTS: At diagnosis, WT1 gene expression exceeded the control level
      in all of the patients. Higher levels of WT1 gene expression were not associated
      with shorter event free survival or overall survival at diagnosis. Higher levels
      of WT1 gene expression were associated with shorter event free survival after
      induction chemotherapy. Relapse was observed in eight of 17 patients analysed
      longitudinally, and an increase of WT1 gene expression preceded morphologic
      relapse in four patients with the fusion transcript negative. Concomitant
      monitoring of PML-RARA fusion transcript reveals the lack of a significant
      correlation withWT1 gene expression. CONCLUSIONS: Quantitation of WT1 gene
      expression could be used for MRD monitoring of AML and for the early detection of
      relapse, especially in patients lacking specific molecular markers.

PMID- 18094594
TI  - Characteristics of acute myeloid leukemia without HLA-DR expression.
AB  - BACKGROUND: HLA-DR negativity is known to be useful for distinguishing acute
      promyelocytic leukemia (APL) from other subtypes of AML, but non-APL cases
      without HLA-DR antigen expression have been reported. The purpose of this study
      was to evaluate and compare the characteristics of APL, HLA-DR negative non-APL,
      and HLA-DR positive non-APL cases. METHODS: A total of 114 cases of AML admitted
      at Ewha Womans University, Mokdong Hospital between March 1997 and June 2006 were
      included in this study. A diagnosis of AML was made based on the results of
      morphology, cytochemistry, immunophenotype, cytogenetics, and/or fluorescence in
      situ hybridization. RESULTS: Among the 114 AML patients, HLA-DR antigen was not
      expressed in 39 (34%), including 24 non-APL (62%) and 15 APL patients (38%). The
      HLA-DR negative non-APL group showed higher leukocyte counts and positive rate of
      CD19 expression than did APL group (P<0.05). The remaining laboratory findings
      were not statistically different between the HLA-DR negative non-APL and APL
      groups. CD34 expression was more frequent in the HLA-DR positive non-APL group
      than in the HLA-DR negative non-APL group and APL group. Of the 24 patients with
      HLA-DR negative non-APL, 7 patients had disseminated intravascular coagulation
      and 2 patients showed morphologic features similar to those of APL. CONCLUSIONS:
      CD19 expression and leukocyte count may be helpful for differentiating HLA-DR
      negative non-APL from APL. However, the final diagnosis and classification should
      be confirmed by cytogenetic or molecular studies.

PMID- 18094595
TI  - [Reconfirmation of preanalytical variables and establishment of reference
      intervals of platelet function analyzer-100 closure times in Korean adults].
AB  - BACKGROUND: Platelet Function Analyzer-100 (PFA-100, Dade-Behring, Germany) is an
      instrument that simulates in vivo hemostatic plug formation under high shear flow
      by measuring the time required to occlude aperture. We performed this study to
      reconfirm preanalytical variables and establish the reference intervals of Korean
      adults. METHODS: A total of 120 healthy individuals were enrolled. Closure times
      (CT) with the collagen/ epinephrine (CEPI) and the collagen/ADP (CADP) cartridges
      were measured. RESULTS: The reference intervals by the central 95th percentile
      were 82-182 sec for CEPI-CT and 62-109 sec for CADP-CT. Females had significantly
      longer CEPI- and CADP-CT than males (P=0.034 and 0.022, respectively).
      Individuals over 40 yr showed shorter CEPI- and CADP-CT compared with younger
      ones (P=0.002 and 0.003, respectively). CEPI- and CADP-CT values measured in the
      afternoon were significantly longer than corresponding ones in the morning
      (P<0.0001 in both conditions). Group O blood groups were related to longer CEPI-
      and CADP-CT compared with non-O blood groups (P=0.0003 and <0.0001,
      respectively). CADP-CT was weakly correlated with hematocrit (r=-0.296, P=0.001),
      but not CEPI-CT. CONCLUSIONS: We reconfirmed the preanalytical variables and
      established the reference intervals of PFA-100 CT in Korean adults. It is
      recommended that reference interval of this test should be verified according to
      age, diurnal variation, and ABO blood groups for optimal utilization.

PMID- 18094596
TI  - [Analysis of positive results in mediace rapid plasma reagin and Treponema
      pallidum latex agglutination as the automated syphilis test].
AB  - BACKGROUND: We compared the results of automated and quantitative methods for the
      diagnosis of syphilis, Mediace Rapid Plasma Reagin (RPR) and Mediace Treponema
      pallidum Latex Agglutination (TPLA) (Sekisui Chemical Co., Ltd, Japan) with those
      of conventional methods. METHODS: Sera from 3,896 persons who had health checkups
      between December 2005 and November 2006 were included in the evaluation of
      positive rates and biological false positives (BFP) for Mediace RPR and TPLA. In
      addition, 134 patients' sera positive for automated Mediace RPR or TPLA were
      tested for VDRL and TPHA. Discrepancies between TPLA and TPHA results were
      confirmed by the RecomBlot Treponemal IgG/IgM (Mikrogen GmbH, Germany). Automated
      Mediace RPR and TPLA were performed using the Hitachi 7600 chemistry autoanalyzer
      (Hitachi, Japan). Samples with positive Mediace RPR and negative TPLA results
      were defined as BFP. RESULTS: Positive rate of automated Mediace RPR was 0.23%
      (9/3,896). BFP of the Mediace RPR was 0.18%. Positive rate of automated TPLA was
      1.62% (37/2,284). Among the 134 patients' sera, 33 (24.6%) showed a discrepancy
      between conventional VDRL and automated Mediace RPR results: Among 31 Mediace
      RPR(+)/VDRL(-) sera, 13 were positive and 18 were negative for TPLA. The
      remaining 2 sera of discrepancy with Mediace RPR(-)/VDRL(+) were all positive for
      TPLA. There were seven sera that showed a discrepancy between automated TPLA and
      TPHA results: Two sera with Mediace RPR(+)/TPLA(-)/TPHA(+) showed negative
      recomBlot Treponemal IgG/IgM results, and among five sera with TPLA(+)/TPHA(-),
      three demonstrated IgG or IgM by recomBlot Treponemal IgG/IgM. CONCLUSIONS: The
      results of comparison data demonstrated that automated TPLA results had a high
      concordance with recomBlot Treponemal IgG/IgM results. Moreover, there are
      additional advantages of automated methods such as quantitative detection, low
      infection risk, and no influence by human handling.

PMID- 18094597
TI  - [Evaluation of Viva-E drug testing system].
AB  - BACKGROUND: The importance and usefulness of therapeutic drug monitoring (TDM)
      have been emphasized, and analysis of drugs has been increased in clinical
      laboratories. We evaluated the analytical performance and clinical usefulness of
      a recently introduced enzyme multiplied immunoassay instrument, Viva-E Drug
      Testing System (Dade Behring Inc., USA). METHODS: Using patients' samples and
      quality control material, we evaluated the analytical performance of Viva-E for a
      total of 11 drugs (cyclosporine, tacrolimus, mycophenolic acid, valproic acid,
      digoxin, theophylline, carbamazepine, phenytoin, phenobarbital, vancomycin, and
      gentamicin) with respect to linearity, precision, and correlations with other
      methods according to CLSI guidelines. Cobas Integra 800 (Roche Diagnostics,
      Switzerland) and API 4000 LC-MS/MS System (Applied Biosystems, USA) were used to
      make a comparison. In addition, we analyzed analysis time. RESULTS: Viva-E showed
      a good linearity (r2 >or= 0.97) for all items. Within-run CVs were within 5% and
      total CVs were within 10% for all drugs except for tacrolimus and digoxin at low
      concentrations. The system correlated well with the other methods (r=0.9283
      0.9778). The time required for reporting the first sample was 11 min and the
      analysis time was 1.1 min. CONCLUSIONS: Since Viva-E showed a good analytical
      performance required for TDM in its linearity, precision, and accuracy with its
      wide drug menus including cyclosporine, tacrolimus, and mycophenolic acid, stat
      and random accessing functions, and the consolidation to a single workstation, it
      could be very useful in the clinical laboratory for various needs.

PMID- 18094598
TI  - [Seven cases of decreased serum valproic acid concentration during concomitant
      use of carbapenem antibiotics].
AB  - Valproic acid (VPA) is a commonly prescribed anticonvulsant drug for the
      treatment of various forms of epilepsy. Concomitant administration of VPA and
      carbapenem antibiotics such as panipenem/ betamipron and meropenem has been
      reported to decrease the serum level of VPA. We observed seven cases which showed
      a decrease in serum levels of VPA due to concomitant use of VPA and carbapenem
      from January 2002 to October 2006 in a 750-bed university hospital, the average
      decrease of 70.4% was observed. Carbapenem antibiotics administrated
      concomitantly with VPA were panipenem (1 case), meropenem (3 cases), and imipenem
      (2 cases), and in one other case imipenem and meropenem were used sequentially.
      We found the VPA serum levels were significantly decreased with meropenem (n=4)
      more than with other carbapenem antibiotics (n=4, 89.3% vs. 51.5% decrease,
      P=0.03). Clinicians should be aware of this potential interaction, pay attention
      to the failure of seizure control due to decreased serum VPA levels with
      concomitant use of carbapenem antibiotics, and monitor VPA serum levels for those
      cases.

PMID- 18094599
TI  - [Prevalence of extended-spectrum beta-lactamases in Escherichia coli and
      Klebsiella pneumoniae from Daejeon].
AB  - BACKGROUND: Extended-spectrum beta-lactamases (ESBLs) are cephalosporinases that
      confer resistance to a wide variety of oxyimino cephalosporins and create serious
      therapeutic problems. Although ESBLs have been reported with increasing frequency
      in Korea, their prevalence and genotypic distribution in Daejeon remain unknown.
      This study was designed to evaluate the occurrence and genotypic distributions of
      ESBL-producing Escherichia coli and Klebsiella pneumoniae in Daejeon. METHODS: We
      tested a total of 427 isolates of E. coli and K. pneumoniae at Chungnam National
      University Hospital during the period from March to September 2006. ESBL
      production was determined by the Clinical and Laboratory Standards Institute ESBL
      confirmatory test; minimum inhibitory concentrations of beta-lactam antibiotics
      were determined by the broth dilution method. The ceftazidime or cefotaxime
      resistance of the ESBL-producers was transferred to azide-resistant E. coli J53
      by conjugation. Searches for ESBL genes were performed by PCR amplification, and
      the genotypes of ESBLs were determined by direct nucleotide sequence analysis of
      the amplified products. The pIs of ESBL were determined by isoelectric focusing.
      RESULTS: The proportion of ESBL-producers was 10% of the E. coli and 28% of the
      K. pneumoniae isolates. The prevalence of ESBL-positive isolates was 60% in the
      intensive care units and 18.7% in the general wards. The most prevalent ESBL
      genotype in E. coli isolates was bla(CTX-M) and in K. pneumoniae was bla(SHV-12).
      CONCLUSIONS: E. coli and K. pneumoniae isolates producing SHV-12 or CTX-M-type
      ESBLs are widespread in Daejeon.

PMID- 18094600
TI  - [A case of bacteremia by Atopobium rimae in a patient with liver cirrhosis].
AB  - Atopobium rimae, previously Lactobacillus rimae, is a strictly anaerobic, non
      spore forming grampositive rod which was frequently isolated from odontogenic
      infection. We report a case of A. rimae bacteremia. A 47-yr-old man with liver
      cirrhosis was admitted to the hospital via emergency room due to fever and chill.
      His abdominal and pelvic computed tomography revealed a small abscess near the
      left adrenal gland. Three sets of blood cultures were taken and non-spore
      forming, grampositive rods were detected in all anaerobic vials. This isolate
      grew small nonhemolytic, gray-white translucent colonies on Brucella blood agar
      and was obligatory anaerobic on air-tolerance test. This organism was negative
      for catalase, indole, nitrate-reduction and beta-lactamase and failed to identify
      by Vitek ANI card (bioMerieux, France). 16S rRNA sequences of this showed 99.8%
      homology of the published sequence of A. rimae (GenBank accession number
      AF292371). Aspirates of periadrenal abscess grew Escherichia coli and
      Peptostreptococcus micros. He was treated with metronidazole and imipenem and
      follow-up cultures of blood were negative at days 4 and 10. To our knowledge,
      this is the first report of bacteremia of A. rimae.

PMID- 18094601
TI  - [Comparison study with enzyme immunoassay and chemiluminescence immunoassay for
      hepatitis B virus surface antigen detection].
AB  - BACKGROUND: The serological detection of the surface antigen (HBsAg) of hepatitis
      B virus (HBV) is the basis of detection of HBV infections in blood donors and
      patients with hepatitis. The aim of this study was to compare the performance of
      HBsAg enzyme-linked immunosorbent assay (ELISA) and HBsAg chemiluminescence
      immunoassay used in Korea. METHODS: We compared seven assays: Architect i2000
      (Abbott Laboratories, USA), Elecsys 2010 immunoanalyzer (Roche Diagnostics,
      Germany), Advia Centaur (Bayer Healthcare, USA), Murex HBsAg version 3 (Abbott
      Laboratories, USA), Enzygnost HBsAg 5.0 (DADE Behring, Germany), LG HBsAg ELISA
      (LG, Korea), and Genedia HBsAg ELISA 3.0 (Greencross Medical Science, Korea). We
      evaluated the sensitivity of each assay by testing serially diluted WHO HBsAg
      reference material, two seroconversion panels, and recombinant HBsAg with three
      mutations in the 'a' determinant. RESULTS: The lowest HBsAg level detected by
      each assay using WHO reference material was variable from 0.05 (Murex and Advia)
      to 0.2 IU/mL. When testing 21 seroconversion panels, the total number of positive
      samples was 15 by Murex and 14 by Architect. Murex, LG, and Architect detected
      all of the 3 mutant samples tested. CONCLUSIONS: Analytical sensitivity and
      mutant detecting ability among HBsAg commercial assays were variable and not
      related to the analytical methods, but related to the manufacturer's reagents. We
      suggest that each laboratory should select an HBsAg assay based on analytical
      performance, test throughput, and the applicability of full automation.

PMID- 18094602
TI  - [Evaluation of BioSewoom HLA-A, -B, -C PCR/SSP kit].
AB  - BACKGROUND: Human leukocyte antigen (HLA) typing based on polymerase chain
      reaction (PCR) is rapidly replacing the conventional serological method. This
      study was intended to evaluate BioSewoom HLA-A, -B, -C PCR/SSP kit (BioSewoom
      SSP) which had recently been developed in Korea. METHODS: A total of 158 samples
      from domestic (21) and international (137) HLA proficiency testing (PT) were
      genotyped with BioSewoom SSP, and its results were compared to consensus results.
      For comparison with INNO-LiPA HLA-A, -B, -C Typing Kit (INNO-LiPA, Innogenetics,
      Belgium), 20 samples of Koreans were genotyped with both kits for each HLA-A, -B,
      -C locus. RESULTS: Among the 21 samples of domestic PT, BioSewoom SSP showed
      ambiguities as follows: 4 samples (19.0%) in HLA-A, 6 (28.6%) in HLA-B, and 1
      (4.8%) in HLA-C. The ambiguities could be resolved by considering the allele
      distribution of Koreans. Among the 137 samples from international PT, BioSewoom
      SSP also showed ambiguities as follows: 12 samples (8.8%) in HLA-A, 26 (19.0%) in
      HLA-B and 6 (4.4%) in HLA-C. Considering the allele distribution of Koreans, the
      serologic equivalents obtained from BioSewoom SSP showed a full agreement with
      those of INNO-LiPA in all the loci tested. Twelve (0.007%) among 1,760 PCR
      reactions from the 21 samples of domestic PT and 20 patient samples produced
      faint nonspecific bands, but it was negligible. PCR failure of internal control
      just barely occurred (15 PCR reactions, 0.009%), but it had no bearing on allele
      assignment. CONCLUSIONS: The performance of BioSewoom SSP was comparable to that
      of INNO-LiPA. All the ambiguities could be resolved by considering the allele
      distribution of Koreans. It is concluded that BioSewoom SSP has good performance
      to be used in routine HLA laboratories.

PMID- 18094603
TI  - [A RhD negative patient failed to produce detectable anti-D after transfusion of
      35 units of RhD positive red blood cells].
AB  - In the present day, pretransfusion tests include ABO and RhD grouping, antibody
      screening, antibody identification, and cross matching. Although error rates for
      these tests have decreased compared to those in the past, clerical errors still
      occur. When exposed to RhD positive RBCs, a RhD negative person can produce anti
      D that causes a severe hemolytic disease of the fetus and the newborn in addition
      to hemolytic transfusion reactions. Therefore, administration of RhD positive
      RBCs to a RhD negative person should be avoided. We experienced a RhD negative
      patient who had been misidentified as positive and transfused 35 units of RhD
      positive RBCs eight years ago, but did not have detectable anti-D in present. The
      red cells of the patient showed no agglutination with the anti-D reagent and a
      negative result in the standard weak D test. The multiplex PCR with sequence
      specific priming revealed that the patient was RhD negative.

PMID- 18094604
TI  - [A case of severe hemolytic disease of the newborn due to anti-Dia antibody].
AB  - Here we report a severe case of hemolytic anemia of the newborn with kernicterus
      caused by anti-Di(a) antibody. A full term male infant was transferred due to
      hyperbilirubinemia on the third day of life. Despite single phototherapy, the
      baby's total bilirubin had elevated to 30.1 mg/dL. After exchange transfusion,
      total bilirubin decreased to 11.45 mg/dL. The direct antiglobulin test on the
      infant's red cells was positive. The maternal and infant's sera showed a negative
      reaction in routine antibody detection tests, but were positive in Di(a) panel
      cells. The frequency of the Di(a) antigen among the Korean population is
      estimated to be 6.4-14.5%. Anti-Di(a) antibody could cause a hemolytic reaction
      against transfusion or hemolytic disease of the newborn. We suggest the need for
      reagent red blood cell panels to include Di(a) antigen positive cells in antibody
      identification test for Korean.

PMID- 18094605
TI  - [Comparison of cardiovascular risk factors between normotension and
      prehypertension].
AB  - BACKGROUND: The individuals with prehypertension are known to progress to
      hypertension, one of the risk factors of cardiovascular disease, more readily
      than the group of normal blood pressure. This study was performed to investigate
      the differences in the risk factors of cardiovascular disease between
      normotensive and prehypertensive groups, and to identify the determinants of
      prehypertension. METHODS: Normotensive (N=3,732) and prehypertensive individuals
      (N=676) were selected from the people who underwent routine medical checkups at
      the Health Promotion Center (Seoul, Korea). The age, body mass index (BMI),
      fasting blood glucose, total cholesterol, triglyceride, LDL-cholesterol (C), HDL
      C, high sensitivity C-reactive protein (hsCRP), lipoprotein(a) [Lp(a)], and the
      number of white blood cell were compared between the normotensive and
      prehypertensive groups. RESULTS: The age, BMI, fasting blood glucose,
      triglyceride, and total cholesterol were higher in the males and females in the
      prehypertensive group than in the normotensive group. LDL-C, however, was higher
      and HDL-C was lower in the females in the prehypertensive group than in the
      normotensive group. The determinants of prehypertension were found to be age,
      BMI, and triglyceride. CONCLUSIONS: There were differences in the risk factors of
      cardiovascular disease between the prehypertensive and normotensive groups.

PMID- 18094606
TI  - Cell death in fetal oocytes: many players for multiple pathways.
AB  - We devised a short-term culture system allowing us to define novel
      characteristics of programmed cell death (PCD) of fetal oocytes and to underscore
      new aspects of this process. Mouse fetal oocytes cultured in conditions allowing
      meiotic progression underwent apoptotic degeneration as revealed by TUNEL
      staining, DNA ladder, Annexin V binding, PARP cleavage and, usually, caspase
      activation. TEM observations show, however, recurrent atypical apoptotic
      morphologies characterized by the absence of chromatin margination and nuclear
      fragmentation; oocytes with autophagic and necrotic features are also observed.
      Moreover, under the fluorescence microscope a subpopulation of TUNEL(+) oocytes
      appear morphologically healthy and do not show detectable caspase activity.
      Finally, caspase inhibitors are able to slow down, but not to abolish, oocyte
      cell death, whereas calpain inhibitor I significantly reduces the number of
      TUNEL(+) oocytes after 4 days of culture, and rapamycin (mTOR inhibitor)
      increases such numbers both at day 3 and 4. These observations together with
      results showing expression in cultured oocytes undergoing cell death of apoptosis
      inducing factor and Beclin 1, two important players of caspase independent and
      autophagic cell death, respectively, demonstrate that fetal oocytes possess and
      are able to activate several players of various forms of cell death. However,
      causal correlation among different cell death pathways in such oocytes remains to
      be determined and stimuli causing the activation of these pathways in vitro and
      in vivo also clarified.

PMID- 18094607
TI  - Roles of ESCRT in autophagy-associated neurodegeneration.
AB  - Autophagy is a regulated pathway for bulk degradation of cytoplasmic contents and
      organelles, an important process involved in many physiological and pathological
      conditions in multiple organs, including the nervous system. It has been proposed
      that developing autophagosomes fuse with late endosomal compartments before their
      fusion with lysosomes; however, little is known about the functional relationship
      between the autophagy and endocytic pathways. In the endosomal-lysosomal pathway,
      a key step in sorting transmembrane cargo proteins is regulated by multimeric
      complexes called ESCRT (endosomal sorting complex required for transport). We
      recently reported that dysfunction of ESCRT-III, either by depletion of its
      essential subunit mSnf7-2 or by expression of a mutant CHMP2B protein associated
      with frontotemporal dementia linked to chromosome 3 (FTD3), caused autophagosome
      accumulation and dendritic retraction before neurodegeneration in cultured mature
      cortical neurons. This defect is likely a result of an abnormal fusion process
      between autophagosomes and endosomal compartments or lysosomes. This study
      suggests that defects in the late steps of the autophagy pathway may contribute
      to the pathogenesis of FTD and potentially other neurodegenerative diseases.

PMID- 18094608
TI  - Rosella: a fluorescent pH-biosensor for reporting vacuolar turnover of cytosol
      and organelles in yeast.
AB  - We have developed a method for monitoring autophagy using Rosella, a biosensor
      comprised of a fast-maturing pH-stable red fluorescent protein fused to a pH
      sensitive green fluorescent protein variant. Its mode of action relies upon
      differences in pH between different cellular compartments and the vacuole. Here
      we demonstrate its utility in yeast (Saccharomyces cerevisiae) by expression in
      the cytosol, and targeting to mitochondria or to the nucleus. When cells were
      cultured in nitrogen depleted medium, uptake of the compartment labelled with the
      biosensor (i.e., cytosol, mitochondria, or nucleus) into the vacuole was
      observed. We showed that this vacuolar uptake was, for cytosol and mitochondria,
      an ATG8-dependent process while the uptake of the nucleus was significantly
      reduced in the absence of Atg8p and can be said to be partially ATG8-dependent.
      We further demonstrated the value of the biosensor as a reporter of autophagy by
      employing fluorescence-activated cell sorting of discrete populations of cells
      undergoing autophagy.

PMID- 18094609
TI  - Transport of autophagosomes in neurites of PC12 cells during serum deprivation.
AB  - Autophagy has been linked to various human diseases, including many
      neurodegenerative disorders. The induction of autophagy has been detected in
      degenerating neurites initiated by different experimental paradigms and hence is
      of major interest. Axonal and dendritic degeneration was significantly delayed
      either by the application of the autophagy inhibitor 3-methyladenine (3-MA) or by
      knocking down the key autophagy-related genes Atg7 and Beclin 1. In addition,
      Tomato-LC3-labelled autophagosomes accumulate in neuritic beadings of PC12 cells
      during nerve growth factor (NGF) deprivation, which might be due to the failure
      of neurite transport. However, little is known about routes and dynamics of
      autophagosomes in the neurites of living cells. Here, we further demonstrate that
      LC3-labelled small autophagosomes are motile and move along the neurites of PC12
      cells in both anterograde and retrograde directions after serum deprivation. The
      autophagosomes paused, re-started, and sometimes changed directions. These
      results provide valuable insight into neuritic transport of autophagosomes and
      imply a close relationship between the autophagic process and neurite
      degeneration.

PMID- 18094610
TI  - Potential subversion of autophagosomal pathway by picornaviruses.
AB  - The RNA replication complexes of small positive-strand RNA viruses such as
      poliovirus are known to form on the surfaces of membranous vesicles in the
      cytoplasm of infected mammalian cells. These membranes resemble cellular
      autophagosomes in their double-membraned morphology, cytoplasmic lumen, lipid
      rich composition and the presence of cellular proteins LAMP 1 and LC3.
      Furthermore, LC3 protein is covalently modified during poliovirus infection in a
      manner indistinguishable from that observed during bona fide autophagy. This
      covalent modification can also be induced by the expression of viral protein 2BC
      in isolation. However, differences between poliovirus-induced vesicles and
      autophagosomes also exist: the viral-induced membranes are smaller, at 200-400 nm
      in diameter, and can be induced by the combination of two viral proteins, termed
      2BC and 3A. Experimental suppression of expression of proteins in the autophagy
      pathway was found to reduce viral yield, arguing that this pathway facilitates
      viral infection, rather than clearing it. We have hypothesized that, in addition
      to providing membranous surfaces for assembly of viral RNA replication complexes,
      double-membraned vesicles provide a topological mechanism to deliver cytoplasmic
      contents, including mature virus, to the extracellular milieu without lysing the
      cell.

PMID- 18094611
TI  - Increased expression of cytoplasmic HuR in familial adenomatous polyposis.
AB  - BACKGROUND: HuR is an mRNA stability factor that binds to the AU-rich element
      containing 3' untranslated region of the transcript. HuR overexpression is
      associated with increased tumor growth. Increased cytoplasmic HuR expression
      occurs in several cancer types, including colorectal cancer where it may
      contribute to the increased cyclooxygenase-2 (COX- 2) expression observed during
      tumorigenesis. To investigate expression of HuR in the colorectal adenoma
      carcinoma sequence, we examined expression of HuR in colorectal mucosa of
      patients with familial adenomatous polyposis (FAP) and sporadic colorectal cancer
      with correlation to COX-2 expression. RESULTS: Cytoplasmic HuR staining was found
      in the epithelium of 10% of normal mucosa, 14.3% of adenomas and 88.9% of
      adenocarcinomas from FAP patients (p < 0.01) and in 68.8% of sporadic colorectal
      carcinomas. High epithelial COX-2 immunostaining was observed in 10% of normal,
      8% of adenomas and all adenocarcinomas from FAP patients (p < 0.01) and in 69.5%
      of sporadic colorectal carcinomas. Positive cytoplasmic HuR immunostaining
      correlated with high COX-2 immunoreactivity in colon mucosa of FAP patients (p <
      0.01) and in sporadic colorectal carcinomas. (p = 0.016) MATERIALS AND METHODS:
      HuR and COX-2 protein expression were studied by immunohistochemistry of normal
      colon mucosa (N=20), adenomas (N=112), carcinomas (N=9) from patients with FAP,
      and 141 sporadic colorectal adenocarcinomas (Dukes B and C). CONCLUSIONS: HuR is
      increasingly expressed in the cytoplasmic epithelial compartment in consecutive
      stages of the adenoma-carcinoma sequence in FAP. Also, COX-2 levels correlate
      with cytoplasmic expression of HuR in colonic epithelium of FAP patients and in
      sporadic colorectal cancer specimens. The role of cytoplasmic expression of HuR
      as a biomarker for progression of adenomas in FAP needs further study.

PMID- 18094612
TI  - Lack of ABC transporter autoinduction in mice following long-term exposure to
      imatinib.
AB  - PURPOSE: Chronic imatinib exposure has been shown to result in upregulation of
      the ABCB1 (P-glycoprotein) and ABCG2 (BCRP) transporters in vitro, for which
      imatinib is a substrate. This finding, along a trend towards increasing imatinib
      clearance over time in patients, has resulted in the suggestion that
      pharmacokinetic resistance may be contributing to eventual treatment failure.
      Here, we sought to determine the effects of long-term imatinib exposure on
      apparent oral clearance and transporter expression in vivo. RESULTS: Plasma and
      liver concentrations of imatinib did not change significantly (P > 0.1) over the
      course of treatment, suggesting that steady-state had been reached. There was no
      increase in Abcb1 or Abcg2 expression in liver samples, whereas expression of
      these transporters in intestinal samples was highly variable, and no increase was
      apparent. METHODS: Male BALB/c mice were treated daily-times 5 with oral imatinib
      at a dose of 50 mg/kg for 4 consecutive weeks. Imatinib concentrations were
      measured in plasma and liver tissue prior to treatment and following each week of
      dosing. Western blotting of liver and intestinal tissue lysates was performed to
      assess expression of Abcb1 and Abcg2. CONCLUSIONS: Imatinib does not appear to
      cause upregulation of ABC transporters in the hepatic and intestinal compartments
      in mice. These data do not support the possibility that autoinduction contributes
      to the development of resistance to imatinib.

PMID- 18094613
TI  - Tumor chemo-immunotherapy using gemcitabine and a synthetic dsRNA.
AB  - Both gemcitabine and synthetic double-stranded RNA (dsRNA) are known to be
      proapoptotic and immuno-stimulatory (-modulatory). We sought to evaluate the
      extent to which a combination therapy using gemcitabine and a synthetic dsRNA,
      polyinosine-cytosine (poly(I:C)), would improve the resultant anti-tumor
      activity. Using model lung and breast cancers in mice, we demonstrated that
      combination treatment of tumor-bearing mice with the poly(I:C) and gemcitabine
      synergistically delayed the tumor growth and prolonged the survival of the mice.
      The combination treatment also synergistically inhibited tumor cell growth in
      vitro and promoted more tumor cells to undergo apoptosis in vivo. Finally, the
      combination therapy generated a strong and durable specific anti-tumor immune
      response, although the immune response alone was unable to control the tumor
      growth after the termination of the therapy. This approach represents a promising
      therapy to improve the clinical outcomes for tumors sensitive to both dsRNA and
      gemcitabine.

PMID- 18094614
TI  - Co-expression patterns of tumor-associated antigen genes by non-small cell lung
      carcinomas: implications for immunotherapy.
AB  - BACKGROUND: Polyvalent vaccination represents a recent attempt to improve the
      effectiveness of lung cancer immunotherapy. This study aimed to investigate
      whether a gene expression pattern of tumor-associated antigens (TAA) would exist
      indicating that their use will be most appropriate for the polyvalent vaccination
      of Caucasian non-small cell lung carcinoma (NSCLC) patients. We examined the
      concomitant expression of genes belonging to different TAA families for which
      expression frequencies either have never been detected in NSCLC or vary widely in
      the literature. RESULTS: 15/23 (65%) and 8/23 (35%) tumor samples were found
      expressing 6-11 and 2-5 out of the 12 examined TAAs, respectively, at levels >1%
      of the testis reference sample. The most prevalent TAA patterns observed were
      those of survivin standard (survivin-std)/survivin-2B expressed by 22/23 (95.5%)
      tumor samples and of survivin-std/survivin-2B/hTERT expressed by 19/23 (82.5%)
      tumor samples. The expression levels of the survivin-std gene strongly positively
      correlated to those of the survivin-2B (p=0.001) and the hTERT genes (p=0.031).
      The number of concomitantly expressed genes was found to be positively correlated
      to the age of the patients (p=0.001) and the tumor size (p=0.048). METHODS: Tumor
      material from 23 patients with NSCLC (12 adenocarcinomas, 8 squamous cell
      carcinomas, 3 bronchiolo-carcinomas) was examined. mRNA transcripts were detected
      for 5 genes of the survivin family, 5 MAGE-A genes as well as the genes of human
      telomerase reverse transcriptase (hTERT) and p53, by the use of quantitative real
      time reverse-transcription polymerase chain reaction (RT-PCR) or semi
      quantitative RT-PCR. CONCLUSION: This study provides evidence that, in Caucasian
      patients with NSCLC, highly prevalent expression patterns of TAA genes,
      predominantly of overexpressed TAAs, do exist. This result implies that the
      combined use of these TAA could help in designing more effective NSCLC
      immunotherapeutic protocols.

PMID- 18094616
TI  - Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with
      188 Re in adult recurrent high-grade glioma.
AB  - Radioimmunotherapy (RIT) may improve the management of malignant gliomas. A Phase
      I clinical trial was performed to evaluate, for the first time, the toxicity and
      clinical effect of an intracavitary administration of a single dose of
      Nimotuzumab (h-R3) labeled wit (188)Re. Nimotuzumab is a humanized monoclonal
      antibody directed against epidermal growth factor receptors. Three patients with
      anaplastic astrocytoma (AA) and 8 with glioblastoma multiforme (GBM) were
      intended to be treated with 3 mg of mAb labelled with 10 or 15 mCi of (188)Re. In
      patients treated with 10 mCi (n=6) transitory worsening of pre-existing
      neurological symptoms were observed. Two patients treated with 15 mCi (n=4)
      developed early severe neurological symptoms and one also developed late severe
      toxicity (radionecrosis). In the group treated with 10 mCi, 1 GBM patient died in
      progression 6 months after the treatment, 2 patients (1 GBM and 1 AA) developed
      stable disease during 3 months. One GBM patient had partial response for more
      than 1 year and 2 patients (1 GBM and 1 AA) were asymptomatic and in complete
      response after 3 years of treatment. Maximal tolerated dose of the
      radioimmunoconjugate (188)Re-Nimotuzumab was 3 mg of the h-R3 labelled with 10
      mCi of (188)Re. The radioimmunoconjugate showed a high retention in the surgical
      created resection cavity and the brain adjacent tissues with a mean value of 85.5
      % of the injected dose one hour post-administration. This radioimmunoconjugate
      may be relatively safe and a promising therapeutic approach for treating high
      grade gliomas.

PMID- 18094617
TI  - 19-nor-1 alpha,25-dihydroxyvitamin D2 (paricalcitol) inhibits the proliferation
      of human pancreatic cancer cells in vitro and in vivo.
AB  - 1,25-dihydroxyvitamin D(3), (1,25(OH)(2)D(3); calcitriol), the hormonal form of
      vitamin D, exerts growth-inhibitory, pro-apoptotic and anti-metastatic effects on
      tumor cells in vitro and in vivo but its clinical use is limited by its calcemic
      effects. Previous studies have shown that the antiproliferative effects of the
      less calcemic calcitriol analog 19-nor-1,25-(OH)(2)D(2) (paricalcitol) on
      prostate tumor cell lines are indistinguishable from those of 1,25(OH)(2)D(3). We
      therefore investigated the anti-proliferative effects of paricalcitol on the
      growth of pancreatic tumor cell lines in vitro and in vivo. Both 1,25(OH)(2)D(3)
      and paricalcitol inhibited the growth of BxPC-3, Hs700T and AsPC-1 lines in a
      dose-dependent manner. This antiproliferative activity correlated with
      upregulation of the cell cycle inhibitors p21 (Waf1/CIP1) and p27(Kip1). A fourth
      pancreatic cell line, Hs766T was unresponsive to both paricalcitol and
      calcitriol. Hs766T cells also failed to upregulate p21/Waf-1/Cip1 or p27/KiP in
      response to treatments with these agents. Paricalcitol, given three times per
      week inhibited the growth of AsPC-1 pancreatic tumor cell xenografts in nude mice
      at a dose that did not cause hypercalcaemia. Tumor inhibition was accompanied by
      in vivo upregulation of p21 and p27 expression. Given the few therapeutic options
      for patients with pancreatic cancer, further exploration of paricalcitol, an FDA
      approved medication, is warranted.

PMID- 18094618
TI  - BMI-1 autoantibody in serum as a new potential biomarker of nasopharyngeal
      carcinoma.
AB  - BMI-1 is overexpressed in a variety of cancers, which can activate the immune
      system to produce antibodies in tumor tissues. In this study, we isolated phage
      expressing BMI-1 protein by screening of a mixture of nasopharyngeal carcinoma
      (NPC) cDNA T7 phage library and found that the antibody against BMI-1 was
      elevated in the sera from NPC patients. BMI-1 mRNA was overexpressed at different
      levels in seven NPC cell lines compared with normal nasopharyngeal epithelial
      cell line NP69. Histochemistry showed that patient sera were more reactive with
      BMI-1 than normal sera. Antibody affinity assay using sera from 40 NPC patients
      and 54 controls showed that BMI-1 antibody was significantly greater in patient
      sera than in normal controls (patient 0.791 +/- 0.025 and normal 0.488 +/- 0.042;
      P < 0.001) and the BMI-1 autoantibody be significantly related with the progress
      of NPC (Benign versus LNPC P=0.001; LNPC versus MNPC P=0.047). Analysis of the
      results with logistic regression and receiver operating characteristics (ROC)
      curves showed that BMI-1 antibody was a modest marker for NPC (sensitivity 0.74
      and specificity 0.73; AUC = 0.8044). The showed that BMI-1 antibody as a
      potential marker of NPC may be rational, and could have diagnostic and prognostic
      value.

PMID- 18094619
TI  - Thymosin Beta 4 is overexpressed in human pancreatic cancer cells and stimulates
      proinflammatory cytokine secretion and JNK activation.
AB  - BACKGROUND: Thymosin beta 4 (T beta 4) has been shown to be associated with tumor
      metastasis and angiogenesis; however, its role in pancreatic cancer has not been
      understood. In the current study, we examined the expression of T beta 4 in
      pancreatic cancer cells, and determined the effect of exogenous T beta 4 on
      cytokine secretion, and signal transduction in human pancreatic cancer cells.
      RESULTS: Pancreatic cancer cell lines expressed higher amount of T beta 4 mRNA
      than normal human pancreatic ductal epithelium (HPDE) cells. Exogenous T beta 4
      increased the secretion of proinflammatory cytokines IL-6, IL-8 and MCP-1 in Panc
      1 cells. In addition, T beta 4 activated Jun N-terminal Kinase (JNK) signaling
      pathways in pancreatic cancer cells. METHODS: The mRNA levels of T beta 4 were
      determined by real-time RT PCR. Phosphorylation of JNK in pancreatic cancer cells
      was determined using Bio-Plex phosphoprotein assay. The expression of cytokines
      in human pancreatic cancer cell lines was determined with Bio-Plex cytokine
      assay. CONCLUSIONS: T beta 4 might be involved in stimulating human pancreatic
      cancer progression by promoting proinflammatory cytokine environment and
      activating JNK signaling pathway. Targeting T beta 4 and related molecules may be
      a novel therapeutic strategy for pancreatic cancer.

PMID- 18094620
TI  - What are imprinted genes doing in the brain?
AB  - As evidence for the existence of brain-expressed imprinted genes accumulates, we
      need to address exactly what they are doing in this tissue, especially in terms
      of organizational themes and the major challenges posed by reconciling imprinted
      gene action in brain with current evolutionary theories attempting to explain the
      origin and maintenance of genomic imprinting. We are at the beginning of this
      endeavor and much work remains to be done but already it is clear that imprinted
      genes have the potential to influence diverse behavioral processes via multiple
      brain mechanisms. There are also grounds to believe that imprinting may
      contribute to risk of mental and neurological disease. As well as being a source
      of basic information about imprinted genes in the brain (e.g., via the newly
      established website, www.bgg.cardiff.ac.uk/imprinted_tables/index.html), we have
      used this chapter to identify and focus on a number of key questions. How are
      brain-expressed imprinted genes organised at the molecular and cellular levels?
      To what extent does imprinted action depend on neurodevelopmental mechanisms? Do
      imprinted gene effects interact with other epigenetic influences, especially
      early on in life? Are imprinted effects on adult behaviors adaptive or just
      epiphenomena? If they are adaptive, what areas of brain function and behavior
      might be sensitive to imprinted effects? These are big questions and, as shall
      become apparent, we need much more data, arising from interactions between
      behavioral neuroscientists, molecular biologists and evolutionary theorists, if
      we are to begin to answer them.

PMID- 18094621
TI  - Control of imprinting at the Gnas cluster.
AB  - Genomic imprinting is a form of epigenetic regulation in mammals whereby a small
      subset of genes is silenced according to parental origin. Early work had
      indicated regions of the genome that were likely to contain imprinted genes.
      Distal mouse chromosome 2 is one such region and is associated with devastating
      but ostensibly opposite phenotypes when exclusively maternally or paternally
      derived. Misexpression of proteins encoded at the Gnas complex, which is located
      within the region, can largely account for the imprinting phenotypes. Gnas is a
      complex locus with extraordinary transcriptional and regulatory complexity. It
      gives rise to alternatively spliced isoforms that show maternal-, paternal- and
      biallelic expression as well as a noncoding antisense transcript. The objective
      of our work at Harwell is to unravel mechanisms controlling the expression of
      these transcripts. We have performed targeted deletion analysis to test candidate
      regulatory regions within the Gnas complex and, unlike other imprinted domains,
      two major control regions have been identified. One controls the imprinted
      expression of a single transcript and is subsidiary to and must interact with, a
      principal control region that affects the expression of all transcripts. This
      principal region contains the promoter for the antisense transcript, expression
      of which may have a major role in controlling imprinting at the Gnas cluster.

PMID- 18094622
TI  - Mouse embryonic stem cells induce targeted DNA demethylation within human MAGE-A1
      transgenes.
AB  - Human tumor development is often associated with a DNA demethylation process.
      This results in the activation of germline-specific genes, such as MAGE-A1, which
      rely on DNA methylation for repression in somatic tissues. Here, we searched to
      identify a cell line possessing ongoing DNA demethylation activity targeted to
      MAGE-A1. We first assessed MAGE-A1-expressing human tumor cell lines, by
      evaluating their ability to induce demethylation of MAGE-A1 transgenes that were
      methylated in vitro before transfection. All cell lines lacked such activity,
      suggesting that MAGE-A1 hypomethylation in tumors results from a past
      demethylation event. We then turned to mouse embryonic stem (mES) cells, which
      are characterized by a high level of methylation plasticity. Interestingly, in
      vitro methylated MAGE-A1 transgenes became demethylated after transfection into
      mES cells. Demethylation was targeted to the 5'-region of MAGE-A1 and was
      strongly reduced at mutated MAGE-A1 transgenes exhibiting impaired promoter
      activity. Our results indicate that mES cells induce demethylation of MAGE-A1 and
      represent therefore a valuable system to study this tumor-related process.

PMID- 18094623
TI  - HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to
      macroautophagy.
AB  - Protein quality control involves molecular chaperones that recognize misfolded
      proteins thereby preventing their aggregation, and associated co-chaperones that
      modulate substrate sorting between renaturation and proteasomal degradation. We
      recently described a new chaperone complex that stimulates degradation of protein
      substrates by macroautophagy. The complex is formed of HspB8, a member of the
      HspB family of molecular chaperones, which is found mutated in neuromuscular
      diseases, and Bag3, a member of the co-chaperone family of Bag domain-containing
      proteins. In this complex, Bag3 was shown to be responsible for macroautophagy
      stimulation. Here we analyzed the role of the three Bag3 canonical protein
      interaction domains. We show that the proline-rich region is essential for the
      Bag3-mediated stimulation of mutated huntingtin clearance. Surprisingly, deletion
      of the BAG domain that mediates Bag3 interaction with Hsp70 and Blc-2, did not
      affect its activity. We propose that in the HspB8- Bag3 complex, HspB8 is
      responsible for recognizing the misfolded proteins whereas Bag3, at least in part
      through its proline-rich domain, might recruit and activate the macroautophagy
      machinery in close proximity to the chaperone-loaded substrates.

PMID- 18094624
TI  - Is mitochondrial generation of reactive oxygen species a trigger for autophagy?
AB  - Autophagy is a conserved lysosomal degradation pathway that has been extensively
      studied in recent years. However, the mechanism of autophagy induction is still
      not clear. Mitochondria are important regulators of both apoptosis and autophagy.
      One of the triggers for mitochondrial mediated apoptosis is the production of
      reactive oxygen species (ROS). Recently, several studies have indicated that ROS
      may be also involved in induction of autophagy. ROS are molecules or ions that
      are formed by the incomplete one-electron reduction of oxygen, including
      superoxide (O2 (*-)), hydrogen peroxide (H2O2), hydroxyl radical ((*)OH), nitric
      oxide (NO), and peroxynitrite (ONOO-). Our recent studies provide strong
      evidences for the involvement of mitochondrially-generated ROS production in the
      induction of autophagy as determined by the formation of autophagosomes and
      autolysosomes. This was accomplished through treatment with mitochondrial toxins
      that inhibit the electron transport chain in transformed and cancer cells. In
      addition, we have determined that H2O2 and 2-methoxyestradiol (inhibitor of
      superoxide dismutases and electron transport chain) induce autophagy leading to
      cell death. In contrast, normal astrocytes fail to induce autophagy following
      treatment with mitochondrial toxins. Herein, we discuss several important points
      of our studies and provide a model for mitochondrially-induced autophagic cell
      death mediated by ROS.

PMID- 18094625
TI  - An autophagic mechanism is involved in apoptotic death of rat striatal neurons
      induced by the non-N-methyl-D-aspartate receptor agonist kainic acid.
AB  - Previous studies found that kainic acid (KA)-induced apoptosis involved the
      lysosomal enzyme cathepsin B, suggesting a possible mechanism of autophagy in
      excitotoxicity. The present study was sought to investigate activation and
      contribution of autophagy to excitotoxic neuronal injury mediated by KA
      receptors. The formation of autophagosomes was observed with transmission
      electron microscope after excitotoxin exposure. The contribution of autophagic
      mechanisms to KA-induced upregulation of microtubule-associated protein 1A/1B
      light chain 3 (LC3), lysosome- associated membrane protein 2 (LAMP2) and
      cathepsin B, release of cytochrome c, activation of caspase-3, down-regulation of
      Bcl-2, upregulation of Bax, p53, puma and apoptotic death of striatal neurons
      were assessed with co-administration of the autophagy inhibitor 3-methyladenine
      (3-MA). These studies showed that KA brought about an increase in the formation
      of autophagosomes and autolysosomes in the cytoplasm of striatal cells. KA
      induced increases in the ratio of LC3-II/LC3-I, LAMP2, cathepsin B, release of
      cytochrome c and activation of caspase-3 were blocked by pre-treatment with 3-MA.
      3-MA also reversed KA-induced down-regulation of Bcl-2 and upregulation of Bax
      protein levels, LC3, p53 and puma mRNA levels in the striatum. KA-induced
      internucleosomal DNA fragmentation and loss of striatal neurons were robustly
      inhibited by 3-MA. These results suggest that over-stimulation of KA receptors
      can activate autophagy. The autophagic mechanism participates in programmed cell
      death through regulating the mitochondria-mediated apoptotic pathway.

PMID- 18094626
TI  - Inducing autophagy harmlessly.
AB  - An important role of autophagy in the clearance of misfolded proteins in neurons
      has been demonstrated. The challenge now is to see if we can develop small
      molecules that can induce autophagy without causing cellular damage.

PMID- 18094627
TI  - Characteristics of a 50S ribosomal subunit precursor particle as a substrate for
      ermE methyltransferase activity and erythromycin binding in Staphylococcus
      aureus.
AB  - Erythromycin is a macrolide antibiotic that inhibits not only mRNA translation
      but also 50S ribosomal subunit assembly in bacterial cells. An important
      mechanism of erythromycin resistance is the methylation of 23S rRNA by erm methyl
      transferase enzymes. A model for 50S ribosomal subunit formation suggests that
      the precursor particle which accumulates in erythromycin treated cells is the
      target for methyl transferase activity. Hybridization experiments identified the
      presence of 23S rRNA in the 50S precursor particle. The protein content of the
      50S precursor particle was analyzed by MALDI-TOF mass spectrophotometry. These
      studies have identified 23 of 36 50S ribosomal proteins in the precursor.
      Methyltransferase assays demonstrated that the 50S precursor particle was a
      substrate for ermE methyltransferase. Competition experiments indicated that the
      enzyme could displace erythromycin from the 50S precursor particle and that the
      methyltransferase had a higher association constant for the precursor particle
      compared to that of erythromycin. Inhibition experiments showed that macrolide,
      lincosamide and streptogramin B compounds bound to the precursor particle with
      similar affinity and inhibited the ermE methyltransferase activity. These studies
      shed light on the interaction of ermE methyltransferase and erythromycin in this
      clinically important pathogen.

PMID- 18094628
TI  - Dealing with stable structures at ribosome binding sites: bacterial translation
      and ribosome standby.
AB  - Bacterial ribosomes have great difficulties to initiate translation on stable
      structures within mRNAs. Translational coupling and induced structure changes are
      strategies to open up inhibitory RNA structures encompassing ribosome binding
      sites (RBS). There are, however, mRNAs in which stable structures are not
      unfolded, but that are nevertheless efficiently initiated at high rates. de Smit
      and van Duin(1) proposed a "ribosome standby" model to theoretically solve this
      paradox: the 30S ribosome binds nonspecifically to an accessible site on the mRNA
      (standby site), waiting for a transient opening of a stable RBS hairpin. Upon
      unfolding, the 30S subunit relocates to form a productive initiation complex.
      Recent reports have provided experimental support for this model. This review
      will describe and compare two different flavors of standby sites, their
      properties, and their likely implications. We also discuss the possibility that
      ribosome standby may be a more general strategy to obtain high translation rates.

PMID- 18094629
TI  - Phosphorus-32: the forgotten radiopharmaceutical?

PMID- 18094630
TI  - Mobile PET in the UK: legislative, regulatory and cost-effectiveness
      considerations.
AB  - Mobile PET/CT or mobile stand alone PET, is becoming more widely available
      throughout the developed world, allowing many small and medium-sized hospitals
      that do not have the scale or financial resources to purchase the static
      diagnostic equipment, to benefit from this imaging technology. Before embarking
      on such a service, a number of legislative, logistical and administrative issues
      have to be addressed to ensure that a mobile PET/CT service is run with optimal
      efficiency and safety and in compliance with the regulations governing the use of
      radioactive substances. Some of these issues are similar to those encountered in
      operating a mobile magnetic resonance imaging scanner but there are important
      differences owing to the use of both sealed and open radioactive sources. This
      article highlights the legislative, administrative and practical issues relevant
      to the UK and also discusses some of the practical issues that need to be
      addressed to ensure the operation of a safe and effective PET service.

PMID- 18094631
TI  - Investigation of normal ranges for left ventricular ejection fraction in cardiac
      gated blood pool imaging studies using different processing workstations.
AB  - BACKGROUND: An investigation has been undertaken to calculate normal ranges for
      left ventricular ejection fraction (LVEF) measured by the gated blood pool (GBP)
      technique. A common set of normal studies was used at 11 hospitals within the
      south of England to assess the variability of results and normal ranges. METHODS:
      Normal studies were identified by retrospective review of patients who had
      undergone a GBP study and echocardiogram at the Royal United Hospital, Bath.
      Patients who had left ventricular function qualitatively identified as normal on
      echocardiogram and normal wall motion for the GBP were included. In total, 64
      datasets were found to match the criteria. All the studies were made anonymous
      prior to being distributed to the participating hospitals. The upper and lower
      limits for normal ejection fraction were defined for each system using the 95%
      confidence limits around the mean value, before and after normalizing the results
      to remove systematic differences between the processing systems. RESULTS: The
      lower cut-off for normal function varied between 40 and 51%. Analysis of the
      individual operator results gave an inter-operator standard deviation of 4.2 and
      an intra-operator standard deviation of 2.7. CONCLUSIONS: It is recommended that
      all studies should be processed at least twice and an average taken to minimise
      these sources of uncertainty. If there is a significant difference the study
      should be reprocessed. Due to random differences between results from different
      systems it is suggested that an equivocal range be used between clearly normal
      and abnormal function.

PMID- 18094632
TI  - Comparison between 180 degrees and 360 degrees acquisition arcs with and without
      correction by CT-based attenuation maps in normal hearts at rest.
AB  - OBJECTIVE: To investigate the effect of acquisition arc (180 degrees or 360
      degrees ) and attenuation correction (AC), in artifact occurrence and image
      uniformity of myocardial perfusion SPECT studies in normal hearts. METHODS:
      Twenty male and 44 female patients with primary hyperparathyroidism and low
      probability of resting perfusion abnormalities were analysed. Tc-sestamibi
      myocardial perfusion studies were performed at rest with a hybrid SPECT/CT
      system. An anthropomorphic phantom was also imaged. RESULTS: Without AC, a 360
      degrees orbit resulted in significantly lower artifact rates compared to the
      standard 180 degrees in both gender groups. Differences persisted (P<0.001) even
      after adjusting reconstruction filter settings to compensate for disproportionate
      count statistics between the two arcs. However, gender-related variation was not
      considerably decreased and sub-diaphragmatic activity was augmented with a 360
      degrees arc. After AC with either arc, substantially lower defect scores and
      minimal gender-related differences were obtained compared to the standard
      technique. A 360 degrees arc yielded lower defect rates and count variability
      than did the 180 degrees arc (P<0.05). These differences were small and were
      eliminated after weighting for dissimilar count statistics. Sub-diaphragmatic
      signal was amplified, particularly with 360 degrees ; severe bowel-myocardial
      activity overlap complicated image interpretation in 14% of cases with 360
      degrees versus 8% with 180 degrees . In certain aspects, phantom imaging findings
      diverged from patient studies. CONCLUSION: Without AC there is significant
      disparity between 180 degrees and 360 degrees concerning artifact occurrence.
      After CT-based AC differences between arcs in defect rate and image uniformity
      seem less critical. However, 180 degrees is favoured by less intensification of
      intestinal activity.

PMID- 18094633
TI  - Evaluating the protective role of ischaemic preconditioning in rat hearts using a
      stationary small-animal SPECT imager and 99mTc-glucarate.
AB  - OBJECTIVE: To examine the protective role of ischaemic preconditioning (IPC) in
      rat hearts using Tc-glucarate (GLA) and a stationary SPECT imager, FastSPECT.
      METHODS: Twenty-four rats with 30 min myocardial ischaemia and 150 min
      reperfusion (IR) were studied as follows. The IPC group (n=6) underwent IPC (five
      cycles of 4 min ligation of the left coronary artery and reflow) before IR. The
      control group (n=7) was treated by IR without IPC. The SPT group (n=6) was
      subjected to IPC and an adenosine antagonist, 8-(p-sulfophenyl)-theophylline
      (SPT). The vehicle group (n=5) received IPC and SPT carrier vehicle. GLA was
      delivered intravenously 30 min post-reperfusion, and 2-h dynamic cardiac images
      were acquired by FastSPECT. RESULTS: GLA showed 'hot-spot' accumulation in the
      ischaemic area-at-risk (IAR) and exhibited lower retention (% 5 min peak) in the
      IPC and vehicle groups (33.8+/-2.6 vs. 35.7+/-9.2, P>0.05) than in the control
      and SPT groups (63.1+/-5.3 vs. 54.8+/-4.8, P>0.05). The infarct size (% IAR) was
      larger in the control and SPT groups (48.2+/-6.3 vs. 41.7+/-6.3, P>0.05) than
      that in the IPC and vehicle groups (21.0+/-1.9 vs. 19.1+/-4.6, P>0.05). In terms
      of the ex-vivo IAR-to-normal radioactivity ratio, there was a statistical
      difference between the control and IPC groups (7.4+/-0.9 vs. 3.0+/-0.4), as well
      as the SPT and vehicle groups (7.4+/-1.0 vs. 3.4+/-0.5). CONCLUSION: IPC offers
      cardioprotection and relates to the activation of adenosine receptors in rat
      hearts. FastSPECT GLA imaging is not only useful in detecting early ischaemia
      reperfusion injury, but also valuable in evaluating cardioprotection.

PMID- 18094634
TI  - Clinical significance of myocardial perfusion abnormalities in patients with
      varying degree of coronary artery stenosis.
AB  - OBJECTIVES: (1) To identify myocardial perfusion abnormalities in a cohort of
      patients having coronary artery disease (CAD) risk factors, with either suspected
      or clinical evidence of ischaemic heart disease (IHD), and with varying degree of
      coronary artery stenosis. (2) To evaluate the clinical significance of the extent
      and severity of perfusion abnormalities assessed by myocardial perfusion
      scintigraphy (MPS) in relation to the anatomical location of coronary stenosis
      demonstrated by five-vessel selective coronary angiography (SCA). METHODS: One
      hundred and thirty-eight patients (106 male, 32 female) with suspected or
      clinical evidence of IHD underwent diagnostic evaluation at the Central Hospital
      of Nicosia, between November 2002 and August 2003. The diagnostic work-up
      included clinical examination, exercise tolerance test, SCA and myocardial
      perfusion scintigraphy (MPS) using either Tl chloride or Tc-tetrofosmin. RESULTS:
      Based on the results of SCA, patients were divided into five groups on the basis
      of stenosis as cross-sectional area of coronary artery lumen and its haemodynamic
      significance, ranging from group 1=less than 50% coronary stenosis to group
      5=100% stenosis (occlusion). Nine of 11 (40.9%) patients with angiographically
      normal coronary arteries (group 1) had moderate inducible reversible ischaemia on
      MPS and 9/47 (19.1%) patients with insignificant coronary stenosis (less than 75%
      stenosis=group 2) had fixed perfusion defects, compatible with previous
      myocardial infarction. The extent of perfusion abnormalities in post-stress MPS
      patients from group 2 was not found to be statistically significant (P>0.05) when
      compared to patients belonging to groups 3, 4 and 5. However, the extent of
      perfusion abnormalities between patients from group 2, when compared to groups 3,
      4 and 5 demonstrated significant statistical difference (P<0.05) on post-rest MPS
      studies. Furthermore, there was no significant statistical correlation between
      anatomical location of coronary stenosis and severity of perfusion abnormalities
      in the corresponding myocardial segments. CONCLUSION: Patients with CAD risk
      factors, and coronary arteries with insignificant stenosis on angiography, may
      demonstrate inducible reversible myocardial ischaemia. This is suggestive of
      coronary endothelial dysfunction. Patients with insignificant coronary artery
      stenosis and no previous history of adverse coronary events may demonstrate
      features of previous myocardial infarction on MPS. The severity of perfusion
      defects demonstrated by MPS may be independent of the anatomical location of
      coronary artery stenosis.

PMID- 18094635
TI  - MRI and hybrid PET/CT for monitoring tumour metastasis in a metastatic breast
      cancer model in rabbit.
AB  - OBJECTIVE: To study tumour growth and metastasis in a rabbit metastatic breast
      cancer (MBC) model and find the most sensitive screening modality in monitoring
      tumour metastasis. METHODS: The MBC model was established by injecting a VX2
      tumour mass suspension into the mammary glands of 23 rabbits and was monitored by
      using physical examination, X-ray, MRI and hybrid PET/CT. RESULTS: Of all 23
      rabbits, axillary lymph node metastasis was detected in 21 (91%) at day 33 after
      tumour inoculation, mediastinal node metastasis in five (22%) at day 42,
      abdominal node metastasis in two (9%) at day 48, lung metastasis in six (26%) at
      day 39, liver metastasis in three (13%) at day 48, and lumbar spine metastasis in
      one (4%) at day 51. Tumour invasion of pleura was found in one, stomach wall in
      one, and pleura and stomach concurrently in one rabbit. Sensitivity for detection
      of lymph node metastases was 78.6% (22/28) and 67.9% (19/28) with MRI and PET/CT,
      respectively; and sensitivity for detection of metastases in distant organs was
      85.7% (12/14) and 71.4% (10/14), respectively. CONCLUSIONS: The MBC model used
      here exhibits fast tumour growth and extensive metastasis in a relatively short
      period. Its metastatic pattern is quite similar to that of human MBC and hence
      could be potentially used as a model for testing imaging modalities and
      translational research, e.g., MBC management. MRI is superior to PET/CT in
      monitoring tumour metastasis.

PMID- 18094636
TI  - Effective doses to patients from CT acquisitions on the GE Infinia Hawkeye: a
      comparison of calculation methods.
AB  - BACKGROUND: Nuclear medicine scans may be accompanied by CT acquisitions to
      provide localization of radioisotope uptake through image fusion and for use in
      attenuation correction. The effective doses to patients resulting from
      radioisotope administrations and from diagnostic CT scans are well documented.
      However, the development of gamma cameras with low dose CT attachments introduces
      the requirement for calculation of effective doses arising from non-standard CT
      acquisitions. In this study, the CT function of the GE Infinia Hawkeye was
      investigated and effective doses were calculated using various methods in order
      to assess the suitability of standard CT dose calculation methods. METHODS: Dose
      measurements were performed using Perspex head and body phantoms and the results
      were used in three calculation methods: (1) the ImPACT CT dosimetry calculator
      used Monte Carlo dose data to calculate effective doses; (2) organ fractions
      exposed by each scan were estimated and applied to dose measurements and ICRP
      tissue weighting factors; (3) standard conversion factors were used with measured
      and displayed dose indices to provide the simplest method of calculation.
      RESULTS: The maximum variation in effective dose using each calculation method
      was within 10% of the mean. Average effective doses from CT scans acquired using
      the Hawkeye were 0.9 mSv for a chest scan, 1.5 mSv for an abdomen-pelvis scan,
      and 0.1 mSv for a head scan, all significantly lower than doses resulting from
      diagnostic CT scans. CONCLUSION: These doses may be used for justification of
      radiation exposures in accordance with IR(ME)R 2000, in association with the
      accompanying radioisotope dose.

PMID- 18094637
TI  - Regional cerebral blood flow in childhood autism: a SPET study with SPM
      evaluation.
AB  - AIM: To establish a link between rCBF assessed with Tc-ECD SPET and the clinical
      manifestation of the disease. METHODS: We performed the study on 11 patients
      (five girls and six boys; mean age 11.2 years) displaying autistic behaviour and
      we compared their data with that of an age-matched reference group of eight
      normal children. A quantitative analysis of rCBF was performed calculating a
      perfusion index (PI) and an asymmetry index (AI) in each lobe. Images were
      analysed with statistical parametric mapping software, following the spatial
      normalization of SPET images for a standard brain. RESULTS: A statistically
      significant (P=0.003) global reduction of CBF was found in the group of autistic
      children (PI=1.07+/-0.07) when compared with the reference group (PI=1.25+/
      0.12). Moreover, a significant difference was also observed for the right-to-left
      asymmetry of hemispheric perfusion between the control group and autistic
      patients (P=0.0085) with a right prevalence greater in autistic (2.90+/-1.68)
      with respect to normal children (1.12+/-0.49). Our data show a significant
      decrease of global cerebral perfusion in autistic children in comparison with
      their normal counterparts and the existence of left-hemispheric dysfunction,
      especially in the temporo-parietal areas devoted to language and the
      comprehension of music and sounds. CONCLUSION: We suggest that these abnormal
      areas are related to the cognitive impairment observed in autistic children, such
      as language deficits, impairment of cognitive development and object
      representation, and abnormal perception and responses to sensory stimuli. Tc-ECD
      SPET seems to be sensitive in revealing brain blood flow alterations and left-to
      right asymmetries, when neuroradiological patterns are normal.

PMID- 18094638
TI  - Comparison of glomerular filtration rate measurements with the two plasma sample
      and single plasma sample, gamma camera Gates, creatinine clearance, and
      prediction equation methods in potential kidney donors with normal renal
      function.
AB  - OBJECTIVE: To compare measured glomerular filtration rate (GFR) by single plasma
      sample methods (SPSMs), gamma camera Gates, 24-h endogenous creatinine clearance,
      and prediction equations (Cockcroft-Gault and modification of renal disease
      (MDRD)) with the two plasma sample method (TPSM) considered as the reference in
      potential kidney donors with normal renal function. METHODS: One hundred and
      fifteen subjects (50 male, 65 female; mean age 41.9+/-12.2 years) with normal
      renal function were prospectively included in this study. GFR was calculated by
      TPSM (120-min and 240-min samples) and SPSM (180-min sample). RESULTS: While
      there was strong statistically significant correlation between the TPSM and all
      SPSMs, low correlation was found in Gates, creatinine clearance, Cockcroft-Gault
      and MDRD. In all SPSMs, 95% limits of agreements were consistent with each other
      and within clinically acceptable limits. The lowest bias, median absolute
      difference, mean percentage error, and the best precision were found for
      Christensen and Groth's method as modified by Watson (CGmW). CONCLUSIONS: Among
      the SPSMs, CGmW can reflect GFR more accurately than the other methods. Neither
      the gamma camera Gates method nor the creatinine clearance method nor the
      prediction equations (Cockcroft-Gault and MDRD) could calculate GFR accurately.
      All these techniques could result in mistakes in the management of potential
      kidney donors.

PMID- 18094639
TI  - Particle sizes of colloids to be used in sentinel lymph node radiolocalization.
AB  - OBJECTIVES: To investigate particle size distribution and possible effects of
      colloid concentration and time after its preparation on the particle sizes of
      albumin nanocolloid (Nanocoll), rhenium sulfide nanocolloid (Nanocis) and tin
      colloid (Hepatate). METHODS: All three kits were prepared according to the
      manufacturers' instructions using the following volumes of decayed Tc generator
      eluate: 1.5 ml, 3.5 ml and 5.0 ml (albumin nanocolloid); 1.0 ml, 2.0 ml and 3.0
      ml (rhenium sulfide nanocolloid); 3.0 ml, 5.0 ml and 9.0 ml (tin colloid). The
      particle sizes were determined by photon correlation spectroscopy inmediately
      after preparation, then at 30 min, 1 h, 2 h, 3 h and 4 h (all three kits) and at
      6 h (Nanocoll and Hepatate). Each measurement was performed in three different
      preparations. RESULTS: The particle sizes of the three colloids did not change
      significantly after preparation throughout their period of validity. For
      Nanocoll, 95% of the particles were between 3 and 16 nm, approximately (mean
      around 8 nm). Small (< or =1 nm) but significant variations on the mean diameter
      were found depending on the volume of pertechnetate used in the preparation. For
      Nanocis, 95% of the particles were between 8 and 68 nm, approximately (mean
      around 23-25 nm). In this kit, there were no significant differences among
      colloidal suspensions prepared with different volumes of pertechnetate. For
      Hepatate, 95% of the particles were between 33 and 255 nm, approximately (mean,
      around 72-90 nm). The upper limit and the mean size increase with the volume of
      eluate used were from 190 nm and 73 nm (3 ml) to 255 nm and 85 nm (9 ml).
      CONCLUSIONS: The particle sizes of Nanocoll, Nanocis and Hepatate are very stable
      throughout their period of validity. For Nanocoll, 95% of particles have a
      diameter <16 nm, with a mean diameter around 8 nm. There are small (< or =1 nm)
      but significant variations on the mean diameter depending on the volume of
      pertechnetate used in its preparation. For Nanocis, 95% of particles have a
      diameter <70 nm, with a mean around 24 nm, and are independent of the volume of
      pertechnetate used in their preparation. For Hepatate, the upper size limit for
      95% of particles is between 190 and 255 nm, with a mean between 72 and 88 nm,
      depending on the volume of pertechnetate used in its preparation. This tin
      colloid could be a good candidate for evaluating clinical suitability in sentinel
      node localization.

PMID- 18094640
TI  - A technique for lung ventilation-perfusion SPECT in neonates and infants.
AB  - BACKGROUND: Single photon emission tomography (SPECT) of the lung is a well
      established non-invasive technique for quantitative assessment of regional lung
      ventilation and perfusion distribution in children and in adults. However, its
      application in neonates as well as infants has been scarce because of several
      practical limitations, such as the trade off between image quality and restricted
      effective radiation doses and the lack of suitable inhalations agents and
      administration techniques. METHODS: In this paper, a new technique for
      quantitative regional lung SPECT based on a passive Technegas administration
      procedure is described and clinically applied. The first clinical findings in
      neonates are reported. RESULTS: This technique overcomes some of the limitations
      of commercial ventilation systems by making patient compliance unnecessary,
      avoiding difficult breathing manoeuvres and by minimizing both facemask dead
      space and inspiratory-expiratory resistance. CONCLUSION: This technique satisfies
      requirements for routine applications in neonates, infants and even older
      patients and has a potential use also for mechanically ventilated patients. It
      has the potential to allow a more precise functionally oriented diagnosis, which
      is of importance for treatment and follow-up in patients with severe lung
      diseases.

PMID- 18094641
TI  - Evaluation of non-uniform weighting in non-linear regression for pharmacokinetic
      neuroreceptor modelling.
AB  - OBJECTIVE: Pharmacokinetic modelling of dynamic PET data has become an important
      tool to analyse in-vivo studies in humans and animals. Estimation of the model
      parameters often requires non-linear regression of an objective function such as
      weighted least squares. Since the noise properties of the data are not known
      exactly in practice, several weighting schemes have been proposed. The objective
      of this study was to evaluate the impact of commonly used weights on
      neuroreceptor quantification with the simplified reference tissue model (SRTM).
      METHODS: We compared the following weights: uniform, Poisson statistics-based
      ideal and noisy weights, iterative weighting, and a noise-free approximation of
      Poisson weights. Ten thousand time-activity curves (TACs) were simulated for
      several noise levels and the three neuroreceptor PET ligands C-(+)McN5652, C
      DASB, and C-raclopride. Each TAC was fitted using weighted non-linear regression
      of the SRTM. We assessed bias and variation of the parameter estimates as well as
      quality of fit and parameter distributions. RESULTS: Results differed
      substantially between ligands and between model parameters. Best parameter
      estimates were obtained with the noise-free approximation of Poisson weights. The
      often-used noisy Poisson weights performed worst for all ligands. Uniform
      weighting gave acceptable parameter estimates for most setups. CONCLUSION:
      'Choice of weights' is important in pharmacokinetic neuroreceptor quantification
      with the SRTM. Weights estimated directly from noisy data should be avoided as
      they can severely degrade parameter estimation and the statistical power of a
      study. If the noise characteristic of the data is unknown, uniform weighting is
      recommended.

PMID- 18094649
TI  - Molecular classification of thyroid nodules by cytology.
AB  - OBJECTIVES: Fine needle aspiration (FNA) biopsy of thyroid nodules provides
      cytologic specimens whose interpretation can direct patients toward either
      thyroidectomy or observation. Approximately 20% of FNA specimens yield an
      indeterminate result. Recent studies have characterized differences in gene
      expression between benign and malignant conditions, most often using whole
      tissue. Our goal was to determine the feasibility of quantitative polymerase
      chain reaction (qPCR)-based gene expression analysis in cytologic samples. For
      five genes shown to be over-expressed in thyroid carcinomas (fibronectin,
      galectin-3, Met/HGFR, MUC1, and GA733-precursor), we compared expression among
      pathologic states. STUDY DESIGN: Prospective laboratory analysis of 20
      thyroidectomy specimens. METHODS: Routine microscopy was performed. Cytologic
      samples were obtained from the dominant nodules, and RNA was extracted.
      Preliminary analysis using fluorometry and reverse-transcriptase (RT)-PCR was
      performed. Expression levels of the test genes in nodules and from control
      samples were measured by real-time qPCR. Fold changes in gene expression were
      compared. RESULTS: Only one specimen did not yield sufficient intact RNA for gene
      expression analysis. RT-PCR revealed satisfactory RNA recovery in all other
      specimens. qPCR showed significant over-expression of fibronectin in the
      papillary carcinomas compared with the goiters (P = .0013), follicular adenomas
      (P = .0014), and follicular carcinomas (P = .0001). Differences in both
      fibronectin and MUC1 expression between the follicular carcinomas and the
      follicular adenomas were also significant (P = .025 and .045, respectively).
      CONCLUSIONS: Cytologic specimens were a satisfactory source of tissue for qPCR
      based gene expression analysis. Both fibronectin and MUC1 were differentially
      expressed in follicular adenomas and follicular carcinomas, and fibronectin
      expression differed in papillary carcinomas compared with the other lesions.
      These results may form the basis of a clinical predictor for lesions with
      indeterminate or suspicious cytology.

PMID- 18094650
TI  - Vascular anatomy of anterolateral thigh flap.
AB  - OBJECTIVES: To understand the vascular anatomy of the anterolateral thigh (ALT)
      free flap. To anatomically determine whether including a 2-cm cuff of vastus
      lateralis muscle (VLM) incorporates musculocutaneous perforators in the harvest
      of the ALT free flap. STUDY DESIGN: Anatomic study on human cadavers. METHODS:
      Twenty-seven cadaver thighs were dissected. Musculocutaneous perforators from the
      vascular pedicle of the ALT free flap were identified. The distance from the
      anterior border of the VLM to the point where perforators entered the muscle was
      measured. RESULTS: An average of four musculocutaneous perforators to the ALT
      free flap were identified per thigh. The distance from the anterior border of the
      VLM to the point where perforators entered the muscle ranged from 0.1 to 7 cm,
      with the mean distance being 1.80 cm. Sixty-four percent of perforators entered
      the VLM within 2 cm of the muscle's anterior border. At least one perforator
      entered the VLM within 2 cm of the muscle's anterior border per thigh.
      CONCLUSIONS: Most musculocutaneous perforators to the ALT free flap enter the VLM
      within 2 cm of the muscle's anterior border, thus providing for an anatomic basis
      for including a 2 cm cuff of VLM when harvesting the ALT free flap. By including
      a 2 cm cuff of VLM, tedious dissection of individual musculocutaneous perforators
      is unnecessary, thereby increasing the ease of dissection and expediting the
      harvest of the ALT free flap.

PMID- 18094651
TI  - Does tumor depth affect nodal upstaging in squamous cell carcinoma of the head
      and neck?
AB  - PURPOSE: The aim of this study was to determine whether tumor depth affects
      upstaging of the clinically node-negative neck, as determined by sentinel lymph
      node biopsy with full pathologic evaluation of harvested nodes including step
      serial sectioning (SSS) and immunohistochemistry (IHC). PATIENTS AND METHODS: One
      hundred seventy-two patients with cT1/2 N0 squamous cell carcinoma (SCC) of the
      oral cavity/oropharynx undergoing primary resection and either sentinel node
      biopsy (SNB) or SNB-assisted neck dissection as a staging tool for the cN0 neck.
      Harvested nodes were examined with hematoxylin-eosin staining, SSS, and IHC.
      Patients upstaged by SSS/IHC were denoted pN1mi. RESULTS: One hundred one of 172
      patients were staged pN0, with 71 (41%) patients upstaged. Increasing tumor depth
      was associated with higher likelihood of upstaging (P < .001). Tumor depth showed
      a positive correlation with nodal stage according to TNM classification (P <
      .001). Tumor depth greater than 4 mm appears to be the most appropriate cutoff
      for risk stratification, although tumors in the oropharynx may require a lower
      value. CONCLUSION: Tumor depth is an important prognostic factor for patients
      with SCC of the oral cavity or oropharynx. Tumors greater than 4 mm are
      associated with greater risk of upstaging; however, this optimum cutoff value may
      vary between primary tumor sites.

PMID- 18094652
TI  - Impact of evolution on the eustachian tube.
AB  - I posit that humans appear to be the only species that develops otitis media. If
      animals in the wild had developed middle-ear disease to any significant degree,
      they would have been selected out during evolution because they would not have
      survived their predators given the associated hearing loss. Why do humans have
      otitis media? Evolution has had a significant impact. It is well known that
      humans are born 12 months too early, which is the result of adaptations to
      bipedalism and our big brain that, over time, resulted in a relatively small
      female pelvic outlet compared with nonhuman primates. As a consequence of too
      early a birth, not only is our immune system immature, but the eustachian tube is
      too short and floppy in the first year of life. But why is otitis media still
      common in older individuals? What other adaptation is uniquely human? We
      developed speech that was associated with descent of the larynx and hyoid bone,
      which, along with a decrease in prognathism (i.e., facial flattening), resulted
      in a change in palatal morphology as compared with other primates. Comparative
      anatomic and physiologic studies have demonstrated significant differences
      between humans and monkeys, especially in the muscles of the eustachian tube.
      Paradoxic constriction, as apposed to dilation, on swallowing is a common tubal
      dysfunction in humans and certain monkey models with chronic middle-ear effusion.
      My hypothesis is that chronic otitis media with effusion in patients with tubal
      constriction is a consequence of adaptation for speech and that, most likely, the
      levator veli palatini muscle is the cause.

PMID- 18094653
TI  - Direct electrical stimulation of Heschl's gyrus for tinnitus treatment.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of the study was to determine the effect of
      electrical stimulation of the auditory cortex in patients with tinnitus. STUDY
      DESIGN: Nonrandomized clinical trial. METHODS: Two patients with debilitating
      tinnitus refractory to conventional therapies were treated. Patients were
      evaluated with validated questionnaires and psychoacoustic measures to determine
      the frequency and pitch of their tinnitus. Tones at these frequencies were then
      presented to the first patient (RP) under magnetoencephalography (MEG) and
      functional magnetic resonance imaging (fMRI) to determine the tonotopic map for
      these frequencies in Heschl's gyrus. These tonotopic sites were targeted for
      implant with a quadripolar electrode. In the second patient (MV), only the fMRI
      tonotopic map was performed. These fMRI results detected an area of increased
      activity, which was selected as the site for the implanted bipolar electrode.
      RESULTS: Patient RP (bilateral tinnitus for 2 years) has experienced a sustained
      reduction to near elimination of tinnitus with intracerebral implanted
      electrodes, whereas patient MV (unilateral tinnitus for 7 years) had an
      unsustained reduction in her tinnitus. CONCLUSION: These findings suggest that
      the perception and annoyance of tinnitus may be modulated or reduced through
      electrical stimulation of the auditory cortex. These unsustained effects for
      patient MV may have been influenced by the longstanding nature of her tinnitus or
      by another reason as yet undetermined.

PMID- 18094654
TI  - Management of tracheobronchial stenoses with endoprostheses: experience with 103
      patients and 11 models.
AB  - OBJECTIVE: To describe in a retrospective study our experience in endoscopic
      management of tracheobronchial stenosis with 145 stents (11 different models).
      METHODS: We analyzed the medical records of 103 patients (67 males and 36
      females) who underwent the placement of prosthesis for any causes of
      tracheobronchial stenoses between 1990 and 2005. RESULTS: A total of 145
      prostheses were placed. Of these, 96.1% of the patients had a relief of dyspnea,
      and 73.8% had only one prosthesis. Stent removal and replacement were
      significantly linked with etiologies (more frequently in patients with an
      inflammatory component), but not with the type of stent. CONCLUSION: Endostenting
      is a safe and effective treatment for tracheobronchial stenoses. Removal and
      replacements were due to etiologies of the strictures, but not to the type of
      stent. Stenoses with an inflammatory component were prone to iterative stenting.
      Only benign diseases that are a contra-indication to open surgery should be
      treated by endoscopic stenting.

PMID- 18094655
TI  - Helicobacter pylori colonization in the larynges of patients with hoarseness.
AB  - OBJECTIVES: Vocal nodules and polyps are two common noninfectious causes of
      hoarseness. Patients with persistent hoarseness often require microscopic
      laryngeal surgery to excise mass lesions of the larynx despite extensive voice
      resting and modification of voice use behavior. Helicobacter pylori has recently
      been reported to present in the upper aerodigestive tract. This study applies the
      rapid urease test to determine the colonization of Helicobacter pylori in
      surgical specimens of patients with vocal nodules and polyps. METHODS: In this
      prospective study, 53 consecutive patients with vocal nodules (n = 20) or vocal
      polyps (n = 33) were investigated from November 2004 to July 2005. Microscopic
      laryngeal surgery was performed in all cases. Tissue specimens harvested from the
      larynx were analyzed using the rapid urease test. RESULTS: The study population
      consisted of 33 females and 20 males with a mean age of 43.1 +/- 9.9 years.
      Thirteen (24.5%) of the 53 patients revealed Helicobacter pylori colonization,
      and all were histopathologically diagnosed with vocal polyps. The difference in
      incidence of Helicobacter pylori colonization between vocal nodules and vocal
      polyps was statistically significant (0% [0/20] vs. 39.4% [13/33], P = .001).
      CONCLUSIONS: Helicobacter pylori often colonizes in the larynxes of patients with
      vocal polyps. These results indicate the involvement of Helicobacter pylori in
      vocal polyps. However, the presence of Helicobacter pylori as an etiologic factor
      in vocal polyps remains inconclusive.

PMID- 18094656
TI  - Practical issues of intraoperative frozen section diagnosis of bone and soft
      tissue lesions.
AB  - BACKGROUND: Intraoperative pathologic diagnosis of bone and soft tissue lesions
      is an important yet challenging tool in clinical musculoskeletal oncology
      practice. There is limited information in the literature addressing the practical
      issues commonly encountered regarding intraoperative frozen section of
      musculoskeletal lesions. METHODS: A literature review and retrospective review of
      practical experience in intraoperative pathology consultation at our institute's
      sarcoma program were conducted to investigate the pitfalls and limitations of
      frozen section and potential solutions to overcome these problems. RESULTS:
      Frozen section evaluation is an essential and reliable procedure for guiding
      intraoperative decisions. Intraoperative cytology as an adjunct to frozen section
      enhances the accuracy of diagnosis of bone and soft tissue lesions. Cytology can
      accurately diagnose certain entities alone and is superior to frozen section for
      certain tumor types and for evaluating bone marrow margins. It is also invaluable
      in triaging cases for ancillary studies and for tumor banking. Practical working
      protocols can be developed to optimize the usefulness of intraoperative
      pathologic consultation. CONCLUSIONS: Intraoperative pathology consultation
      should be done in an interdisciplinary approach by correlating clinical,
      radiologic, and pathologic information. As an adjunct to frozen section, cytology
      and gross examination enhance the accuracy of diagnosis of musculoskeletal
      lesions.

PMID- 18094657
TI  - Orthopedic surgery options for the treatment of primary osteosarcoma.
AB  - BACKGROUND: Osteosarcoma is the most common malignant primary neoplasm of bone.
      Orthopedic procedures are essential components in the multidisciplinary treatment
      of osteosarcoma. Limb-salvaging procedures offer adequate disease control
      comparable to the results obtained by amputations. This review discusses the
      advantages and disadvantages of the various types of amputations and the limb
      salvaging techniques for the treatment of osteosarcoma. METHODS: The authors
      analyzed the characteristics of limb-salvaging procedures and amputations for
      osteosarcoma. Qualitative and quantitative studies published in the English
      language that are listed in the National Library of Medicine were used as the
      basis for this review. In addition, a review of an expandable prosthesis is
      included. RESULTS: Limb-salvaging techniques have acceptable rates of disease
      control. However, amputation remains a valid procedure in selected cases of
      osteosarcoma in most parts of the world. Orthopedic oncology surgeons have
      various materials, procedures, and techniques available to achieve disease
      control and improve function in patients with osteosarcoma. CONCLUSIONS: The
      surgical management of patients with osteosarcoma is challenging. No difference
      in survival has been shown between amputations and adequately performed limb
      salvaging procedures. Optimal tumor resection and a functional residual limb with
      increased patient survival are the goals of modern orthopedic oncology.

PMID- 18094658
TI  - Advanced-technology radiation therapy for bone sarcomas.
AB  - BACKGROUND: Bone sarcomas are rare primary tumors. Radiation therapy (RT) can be
      useful in securing local control in cases where negative surgical margins cannot
      be obtained or where tumors are not resected. Recent technical advances in RT
      offer the opportunity to deliver radiation to these tumors with higher precision,
      thus allowing higher doses to the tumor target with lower doses to critical
      normal tissues, which can improve local tumor control and/or reduce treatment
      related morbidity. METHODS: The authors conducted a survey of recent technical
      developments that have been applied to the RT for bone sarcomas. RESULTS: RT
      techniques that show promise include intensity-modulated photon radiation
      therapy, 3-D conformal proton RT, intensity-modulated proton RT, heavy charged
      particle RT, intraoperative RT, and brachytherapy. All of these techniques permit
      the delivery of higher radiation doses to the target and less dose to normal
      tissue than had been possible with conventional 3-D conformal radiation
      techniques. Protons deliver substantially less dose to normal tissues than
      photons. CONCLUSIONS: Data from clinical studies using these advanced radiation
      techniques suggest that they can improve the therapeutic ratio (the ratio of
      local control efficacy to the risk of complications). This is expected to improve
      the treatment outcome for these challenging tumors.

PMID- 18094659
TI  - Outpatient chemotherapy plus radiotherapy in sarcomas: improving cancer control
      with radiosensitizing agents.
AB  - BACKGROUND: Cancer control by radiotherapy (RT) can be improved with concurrent
      chemotherapy. Outpatient strategies for sarcomas that combine chemotherapy and RT
      are possible since supportive care and RT techniques have improved. METHODS: The
      current status of non-anthracycline chemotherapy in combination with radiation
      for high-risk sarcoma is reviewed. RESULTS: Ifosfamide with mesna and newer
      activated ifosfamide agents (ZIO-201 and glufosfamide) have high potential to
      improve sarcoma cancer control. In Ewing's sarcoma and osteosarcoma, high-dose
      ifosfamide with mesna (2.8 g/m2/day of each x 5 days; mesna day 6) can be safely
      given to outpatients using continuous infusion. Reducing ifosfamide
      nephrotoxicity and central nervous system side effects are discussed. Other
      outpatient radiosensitization regimens include gemcitabine (600-1000 mg/m2/dose
      IV over 1 hour weekly x 2-3 doses), temozolomide (75 mg/m2/daily x 3-6 weeks), or
      temozolomide (100 mg/m2/dose daily x 5) + irinotecan (10 mg/m2/dose daily x 5 x 2
      weeks). In osteosarcoma with osteoblastic metastases on bone scan, samarium (1
      mCi/kg; day 3 of RT) and gemcitabine (600 mg/m2 IV over 1 hour day 9 of RT) is a
      radiosensitization strategy. Future drugs for radiosensitization include beta-D
      glucose targeted activated ifosfamide (glufosfamide) and sapacitabine, an oral
      nucleoside with in vitro activity against solid tumors including sarcomas.
      CONCLUSIONS: The potential to treat major causes of sarcoma treatment failure
      (local recurrence and distant metastases) with concurrent chemotherapy during
      radiation should be considered in high-grade sarcomas.

PMID- 18094660
TI  - Therapeutic potential of directed tyrosine kinase inhibitor therapy in sarcomas.
AB  - BACKGROUND: Sarcomas are rare mesenchymally derived tumors for which there are
      limited treatment options. This paper discusses the current therapeutic potential
      of directed tyrosine kinase inhibitors (TKIs) in sarcoma. METHODS: The authors
      review antibody-based strategies and small molecular inhibitors of TKIs, with
      specific emphasis placed on the potential use of these targeted agents as
      therapeutic options for the treatment of sarcomas that are not gastrointestinal
      stromal tumors. RESULTS: Many TKs have been shown to be mutated or overexpressed
      in human sarcoma tumors and cell lines and may serve as potential targets for
      promising new sarcoma therapies. Furthermore, the novel mechanism of targeting
      TKs may complement the antitumor activity of existing sarcoma treatment options.
      CONCLUSIONS: TKIs such as imatinib, sunitinib, and sorefanib are promising new
      therapeutic options for the management of patients with soft tissue sarcoma.

PMID- 18094661
TI  - Current issues in adolescent and young adult cancer survivorship.
AB  - BACKGROUND: Overall, the survival rate for cancer patients has continued to
      improve over the past several decades. However, those aged 15 to 29 years have
      not experienced the same improvements in survival. This review explores some of
      the challenges faced by adolescent and young adult (AYA) cancer patients and
      their survivorship needs. METHODS: Using the OVID Medline database from 1966 to
      present, a variety of search terms including "adolescent," "young adult," and
      "cancer survivorship" were entered. Articles related to those obtained by the
      search were also collected. Additional data were obtained from the SEER database
      AYA monograph, the Childhood Cancer Survivorship Study, the Report of the
      Adolescent and Young Adult Oncology Progress Review Group, and the Long-Term
      Follow-Up Recommendations of the Children's Oncology Group. RESULTS: Cancer
      patients in this age-group are at increased risk for second malignancies,
      cardiotoxicity, and reproductive difficulties. Few data exist concerning
      intellectual and other psychosocial issues for this specific patient population.
      CONCLUSIONS: More research is needed to develop accurate data on treatment and
      survivorship for AYA patients. A separate cancer discipline focusing on improving
      outcomes in treatment and survivorship among AYA patients should be developed in
      major academic cancer centers.

PMID- 18094662
TI  - Cultural values and secondary prevention of breast cancer in african american
      women.
AB  - BACKGROUND: Improving mammography initiation and maintenance among African
      American women has been suggested as a strategy for reducing breast cancer
      mortality in this population. METHODS: We examined cultural values in relation to
      self-reported breast cancer screening among 572 low-income, urban, African
      American women. Cultural values examined included time orientation, family
      authority, employment aspirations, value of past vs modern life, and reliance on
      medical professionals. Also, implications for continued development of culturally
      tailored health interventions and opportunities for the consideration of cultural
      values in health communication are discussed. RESULTS: Bivariate analyses showed
      that more traditional values were associated with worse screening histories and
      lower intentions for future screening. In multivariate analyses, two interactions
      were observed between cultural values and age: for younger women, more
      traditional values were associated with lower odds of having ever received a
      mammogram, and for older women, more traditional values were associated with
      lower odds of intentions to receive a mammogram in the next 2 years. CONCLUSIONS:
      This study adds to the evidence that cultural constructs, such as values, are
      associated with secondary prevention of breast cancer and supports the
      consideration of cultural constructs as important in increasing mammography and
      reducing breast cancer disparities for African American women.

PMID- 18094663
TI  - Colorectal cancer screening and African Americans: findings from a qualitative
      study.
AB  - BACKGROUND: Colorectal cancer (CRC) screening has been found to be an effective
      tool for the control and prevention of this type of cancer, yet it is
      underutilized by African Americans. Consequently, African Americans with CRC are
      diagnosed at late stages and suffer disproportionately higher mortality rates for
      CRC. METHODS: To understand factors that influence the decision to participate in
      CRC screening, in-depth personal interviews were conducted with 36 African
      Americans in the Washington, DC, metropolitan area. Predisposing factors,
      enabling factors, and reinforcing factors were identified and categorized using
      the Predisposing, Reinforcing, and Enabling Constructs in
      Educational/Environmental Diagnosis and Evaluation (PRECEDE) framework. RESULTS:
      Findings suggest that distinct differences exist between individuals who are
      adherent to screening guidelines and those who have not undergone screening.
      Adherent individuals were more knowledgeable about CRC and held positive beliefs
      about the benefits of screening. Nonadherent individuals placed little importance
      on prevention and early detection. Physician recommendation and insurance
      coverage/cost also differentiated the two groups. CONCLUSIONS: Study findings
      suggest that efforts to increase awareness and promote the benefits of CRC
      screening are needed among African Americans. Also, efforts by healthcare
      providers to recommend CRC screening are important in promoting adherence.
      Further, low- or no-cost CRC screening is needed to increase participation by
      individuals who are economically disadvantaged.

PMID- 18094664
TI  - Transcatheter arterial chemoembolization and percutaneous ethanol injection for
      Hepatocellular carcinoma: a retrospective review of the Veterans Affairs
      Caribbean Healthcare System.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy worldwide and
      has a poor prognosis. Although surgery and liver transplantation provide better
      outcomes, most patients are not candidates due to advanced disease, lack of donor
      availability, or presence of comorbidities. Several percutaneous approaches such
      as transcatheter arterial chemoembolization (TACE) and percutaneous ethanol
      injection therapy (PEIT) have been developed for local control and can
      potentially increase survival in these patients. METHODS: We retrospectively
      reviewed 33 patients with HCC who were treated with TACE, PEIT, or both from 2000
      to 2005 at the VA Caribbean Healthcare System in Puerto Rico to evaluate
      tolerability, response, and survival. Patients were evaluated with cross
      sectional computed tomography imaging to determine response using response
      evaluation criteria in solid tumors (RECIST). RESULTS: Thirty-three men with a
      mean age of 66 years were treated. Mean tumor size was 5.6 cm, ranging from 2 cm
      to 16 cm. All patients had cirrhosis, with alcohol abuse and hepatitis C as the
      most common etiologies. Objective radiographic partial response was observed in
      28% of patients and 48% had disease stabilization. Most of the patients had a
      therapeutic response demonstrated by necrosis of the tumor and decreased contrast
      enhancement. Patients who underwent both TACE and PEIT had a higher response rate
      and disease stabilization but no difference in survival compared with those who
      received TACE or PEIT alone. Median survival for the whole group was 2 years.
      Causes of death included tumor progression, hepatic failure, gastrointestinal
      bleeding, and infections. The initial tumor size and Child-Pugh class did not
      confer a significant difference in survival rate. CONCLUSIONS: In Puerto Rico,
      where liver transplantation is not performed at present, percutaneous treatments
      are effective local therapies for patients who are not candidates for surgery and
      who have disease limited to the liver.

PMID- 18094665
TI  - Detection of the moderately beneficial cognitive effects of low-dose treatment
      with haloperidol or clozapine in an animal model of the attentional impairments
      of schizophrenia.
AB  - The absence of effective cognition enhancers for the treatment of patients with
      schizophrenia limits the validation of animal models and behavioral tests used
      for drug finding and characterization. However, low doses of haloperidol and
      clozapine were documented to produce moderately beneficial effects in patients.
      Therefore, this experiment was designed to determine the attentional effects of
      such treatments in a repeated-amphetamine (AMPH) animal model. Animals were
      trained in an operant-sustained attention task and underwent a 40-day
      pretreatment period with saline or increasing doses (1-10 mg per kg) of AMPH.
      After regaining baseline performance following 10 days of saline treatment,
      animals were treated with haloperidol (0.025 mg per kg), clozapine (2.5 mg per
      kg), or vehicle for 10 days. Furthermore, the effects of AMPH challenges (1.0 mg
      per kg) were assessed. In AMPH-pretreated animals, the administration of AMPH
      challenges resulted in the disruption of attentional performance. Treatment with
      haloperidol and clozapine attenuated the detrimental performance effects of these
      challenges, with clozapine exhibiting more robust attenuation. Furthermore,
      clozapine, but not haloperidol, impaired the performance of control animals. In
      contrast, the performance of AMPH-pretreated animals remained unaffected by
      clozapine. As this animal model detects the moderately beneficial cognitive
      effects of haloperidol and clozapine, it may be useful for preclinical research
      designed to detect and characterize treatments for the cognitive symptoms of
      schizophrenia.

PMID- 18094666
TI  - Reversal of subchronic PCP-induced deficits in attentional set shifting in rats
      by sertindole and a 5-HT6 receptor antagonist: comparison among antipsychotics.
AB  - Currently accepted treatments for schizophrenia can effectively control positive
      symptoms but have limited impact on cognitive deficits in schizophrenia. The
      purpose of these experiments was to address this unmet need by characterizing the
      effects of classical and second-generation antipsychotics on cognitive
      impairments associated with schizophrenia. An additional aim was to characterize
      the part(s) of the pharmacological profile of drugs that were important to
      reverse deficits. Cognitive deficits were assessed using a frontally mediated
      attentional set-shifting task in rats that is analogous to tasks used in humans
      and nonhuman primates that assess executive function. Mirroring findings in
      patients with schizophrenia, the classical antipsychotic haloperidol was
      ineffective in treating set-shifting deficits induced by subchronic treatment
      with phencyclidine (PCP). Similarly, second-generation antipsychotics,
      risperidone, clozapine, and olanzapine were ineffective. In contrast, selected
      doses of sertindole and the 5-HT(6) receptor antagonist SB 271046 attenuated PCP
      induced set-shifting deficits. Finally, the 5-HT(2A) receptor antagonist M100907
      was without effect. Further examination revealed that repeated treatment (21
      days) with sertindole, but not olanzapine, also was effective in reversing the
      executive function deficit. These data suggest that the combination of 5-HT(6)
      antagonistic activity and the absence of antimuscarinic activity may represent
      key characteristics of the pharmacological profile for improved antipsychotic
      drugs for schizophrenia.

PMID- 18094667
TI  - Prominent activation of brainstem and pallidal afferents of the ventral tegmental
      area by cocaine.
AB  - Blockade of monoamine transporters by cocaine should not necessarily lead to
      certain observed consequences of cocaine administration, including increased
      firing of ventral mesencephalic dopamine (DA) neurons and accompanying impulse
      stimulated release of DA in the forebrain and cortex. Accordingly, we hypothesize
      that the dopaminergic-activating effect of cocaine requires stimulation of the
      dopaminergic neurons by afferents of the ventral tegmental area (VTA). We sought
      to determine if afferents of the VTA are activated following cocaine
      administration. Rats were injected in the VTA with retrogradely transported
      Fluoro-Gold and, after 1 week, were allowed to self-administer cocaine or saline
      via jugular catheters for 2 h on 6 consecutive days. Other rats received a
      similar amount of investigator-administered cocaine through jugular catheters.
      Afterward, the rats were killed and the brains processed immunohistochemically
      for retrogradely transported tracer and Fos, the protein product of the neuronal
      activation-associated immediate early gene, c-fos. Forebrain neurons exhibiting
      both Fos and tracer immunoreactivity were enriched in both cocaine groups
      relative to the controls only in the globus pallidus and ventral pallidum, which,
      together, represented a minor part of total forebrain retrogradely labeled
      neurons. In contrast, both modes of cocaine administration strongly increased
      double-labeling relative to the controls in the brainstem, specifically in the
      caudal ventromedial mesencephalon and rostromedial pontine tegmentum. It is
      concluded that a previously unappreciated activation of pallidal and brainstem
      afferents may contribute to the modulation of dopaminergic neuronal activity
      following cocaine administration.

PMID- 18094668
TI  - Proton magnetic resonance spectroscopy during initial treatment with
      antipsychotic medication in schizophrenia.
AB  - Reduced brain N-acetyl-aspartate (NAA) has been repeatedly found in chronic
      schizophrenia and suggests neuronal loss or dysfunction. However, the potential
      confounding effect of antipsychotic drugs on NAA has not been resolved. We
      studied 32 minimally treated schizophrenia patients and 21 healthy subjects with
      single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) of the frontal and
      occipital lobes, caudate nucleus, and cerebellum. Concentrations of NAA, Choline,
      and Cre were determined and corrected for the proportion of cerebrospinal fluid
      (CSF) in the voxel. Patients were treated in a randomized-controlled double-blind
      manner with either haloperidol or quetiapine. (1)H-MRS was repeated every 6
      months for up to 2 years. There was a group main effect for baseline NAA with
      lower global NAA in schizophrenia subjects before treatment compared to healthy
      controls. Global NAA was directly related to measures of global cognitive
      performance in the whole subject sample. Following treatment with haloperidol or
      quetiapine, there were no changes in NAA in any of the regions studied. Early in
      the illness, schizophrenia patients already demonstrate subtle reductions in NAA.
      Treatment with typical or atypical antipsychotic medications for several months
      does not result in NAA changes.

PMID- 18094669
TI  - Drug-eluting stent pathology--should we still be cautious?

PMID- 18094670
TI  - Stress (Takotsubo) cardiomyopathy--a novel pathophysiological hypothesis to
      explain catecholamine-induced acute myocardial stunning.
AB  - Stress cardiomyopathy, also referred to as Takotsubo cardiomyopathy, is an
      increasingly recognized clinical syndrome characterized by acute reversible
      apical ventricular dysfunction. We hypothesize that stress cardiomyopathy is a
      form of myocardial stunning, but with different cellular mechanisms to those seen
      during transient episodes of ischemia secondary to coronary stenoses. In this
      syndrome, we believe that high levels of circulating epinephrine trigger a switch
      in intracellular signal trafficking in ventricular cardiomyocytes, from G(s)
      protein to G(i) protein signaling via the beta(2)-adrenoceptor. Although this
      switch to beta(2)-adrenoceptor-G(i) protein signaling protects against the
      proapoptotic effects of intense activation of beta(1)-adrenoceptors, it is also
      negatively inotropic. This effect is greatest at the apical myocardium, in which
      the beta-adrenoceptor density is greatest. Our hypothesis has implications for
      the use of drugs or devices in the treatment of patients with stress
      cardiomyopathy.

PMID- 18094671
TI  - Statins and polyunsaturated fatty acids for treatment of atrial fibrillation.
AB  - Atrial fibrillation (AF) affects 1.5-2.0% of the population in the developed
      world. Projected data from population-based studies in the US indicate that the
      number of adults with AF will swell by 2.5-3.0-fold by 2050. Despite advances in
      pharmacological and nonpharmacological therapies for rhythm or rate control in
      patients with AF, primary prevention with 'upstream' therapy and risk factor
      modification is likely to produce a far greater effect in the general population
      than specific interventions. Rapidly developing experimental work has provided
      new insights into AF pathophysiology that will lead to new mechanism-based
      therapies. Agents targeting inflammation, oxidative injury, atrial myocyte
      metabolism, extracellular matrix remodeling, and fibrosis, have theoretical
      advantages as novel therapeutic strategies. Angiotensin-converting-enzyme
      inhibitors, angiotensin-receptor blockers, beta-blockers, statins, and omega-3
      polyunsaturated fatty acids have shown antiarrhythmic potential, over and above
      any effect related to the treatment of underlying heart disease. These agents
      could be exploited to prevent or delay atrial remodeling in patients with AF,
      even in the absence of routine indications for such therapy. This Review provides
      a contemporary evidence-based insight into the possible preventive and reverse
      remodeling roles of statins and polyunsaturated fatty acids in AF.

PMID- 18094672
TI  - Late medical versus interventional therapy for stable ST-segment elevation
      myocardial infarction.
AB  - ST-segment elevation myocardial infarction (STEMI) is associated with high
      morbidity and mortality, but timely reperfusion is known to result in
      dramatically improved patient outcomes. As many as 40% of patients with STEMI,
      however, present late after symptom onset, which reduces the likelihood of them
      receiving reperfusion therapy. The past two decades have been plagued with
      controversy regarding the relative benefits of reperfusion therapy after 12 h
      from symptom onset. Despite considerable data supporting late reperfusion and the
      'late open-artery hypothesis', recent studies have demonstrated a lack of benefit
      with late reperfusion. Moreover, advances in the medical management of STEMI have
      dramatically reduced morbidity and mortality, further challenging the need for
      more-invasive techniques. Numerous questions have arisen regarding the
      appropriate management and risk stratification of asymptomatic post-STEMI
      patients who present late after symptom onset. In light of recent data, we
      present a Review of late reperfusion in STEMI, specifically highlighting the
      effects of current medical therapies, risk-stratification techniques, and
      indications for the use of late reperfusion over medical management.

PMID- 18094673
TI  - Pheochromocytoma: cyclic attacks of hypertension alternating with hypotension.
AB  - BACKGROUND: A 52-year-old woman was admitted to hospital with recurrent episodes
      of chest and abdominal pain, dyspnea, palpitations and diaphoresis. Continuous
      blood pressure recordings revealed rhythmic alternation between episodes of
      severe hypertension and episodes of hypotension. This cyclic hemodynamic crisis
      continued for 2 hours, with each cycle lasting around 15 min. INVESTIGATIONS:
      Physical examination, electrocardiography, chest radiography, continuous intra
      arterial pressure monitoring, blood and urine analysis, echocardiography,
      abdominal CT and 131I miodobenzylguanidine scanning. DIAGNOSIS: Pheochromocytoma-
      a catecholamine secreting tumor. MANAGEMENT: Intravenous phentolamine and fluids,
      oral doxazosin and surgical removal of the tumor.

PMID- 18094674
TI  - Low birth weight is associated with chronic kidney disease only in men.
AB  - The association of low birth weight and chronic kidney disease was examined in a
      screened volunteer population by the National Kidney Foundation's Kidney Early
      Evaluation Program. This is a free, community-based health program enrolling
      individuals aged 18 years or older with diabetes, hypertension, or a family
      history of kidney disease, diabetes, or hypertension. Self-reported birth weight
      was categorized and chronic kidney disease defined as an estimated glomerular
      filtration rate less than 60 ml per min per 1.73 m(2) or a urine
      albumin/creatinine ratio >or=30 mg/g. Among 12 364 participants, 15% reported a
      birth weight less than 2500 g. In men, significant corresponding odds ratios were
      found after adjustment for demographic characteristics and health conditions to
      this low birth weight and chronic kidney disease, but there was no association
      among women. There was no significant interaction between birth weight and race
      for either gender. Efforts to clinically understand the etiology of this
      association and potential means of prevention are essential to improving public
      health.

PMID- 18094675
TI  - The effect of losartan on hemoglobin concentration and renal outcome in diabetic
      nephropathy of type 2 diabetes.
AB  - Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can
      decrease hemoglobin, causing anemia and this may be an independent risk factor
      for chronic kidney disease progression. We studied the relationship between a
      decline in hemoglobin and outcome in 1513 patients with type 2 diabetes and
      kidney disease by a post hoc analysis of the RENAAL Study (Reduction of Endpoints
      in NIDDM with the Angiotensin II Antagonist Losartan) with an average follow-up
      of 3.4 years. The relationship between baseline and year-1 hemoglobin and
      treatment on end-stage renal disease (ESRD) and ESRD or death was evaluated using
      multivariate Cox models (covariates: baseline hemoglobin, proteinuria, serum
      albumin, serum creatinine, and year-1 hemoglobin). Compared with placebo,
      losartan treatment was associated with a significant decrease of hemoglobin, with
      the largest between-group difference at 1 year. After adjustment, there were
      significant relative risk reductions for losartan compared with placebo for ESRD
      and for ESRD or death regardless of the baseline hemoglobin even in those
      patients with a baseline hemoglobin below 120 g l(-1). Hence, the renoprotective
      properties of losartan were maintained despite a significant lowering of the
      hemoglobin concentration.

PMID- 18094676
TI  - Early transcriptional control of ENaC (de)ubiquitylation by aldosterone.
AB  - Aldosterone increases sodium reabsorption across kidney target tubules already
      before it increases the number of transport proteins, indicating that the early
      functional response to aldosterone depends on the activation of preexisting
      channels and pumps. A central mediator of this action is the early aldosterone
      induced kinase Sgk1 that de-represses the surface expression and activity of the
      epithelial sodium channel (ENaC). A main mechanism by which Sgk1 exerts this de
      repression is the phosphorylation of the ubiquitin ligase Nedd4-2 that is thereby
      prevented from ubiquitylating ENaC. Among a series of new early aldosterone
      induced gene products recently identified in kidney target tubules, an additional
      regulator of ENaC ubiquitylation, the deubiquitylating enzyme Usp2-45, was
      identified. Coexpression of Usp2-45 was shown to increase ENaC surface expression
      and activity, and to decrease its ubiquitylation in expression systems, whereas
      other Usps such as the splice variant Usp2-69 had no effect. Since both Sgk1 and
      Usp2-45 are similarly induced in distal colon as well, in contrast to other gene
      products strongly induced in kidney that are not regulated in colon, we suggest
      that (de)ubiquitylation is the major ENaC regulatory mechanism targeted by
      aldosterone in the short-term via transcriptional regulation.

PMID- 18094677
TI  - B cells and tertiary lymphoid organs in renal inflammation.
AB  - B lymphocytes are part of the inflammatory cells recruited to the human kidney in
      various disease settings. B cell infiltrates have been described in renal
      allografts, in acute and chronic interstitial nephritis, and the most common
      glomerular diseases like immunoglobulin A (IgA) and membranous nephropathy. These
      cells are almost exclusively recruited to the tubulointerstitium, but not the
      glomerular tuft. In addition to diffuse tubulointerstitial infiltrates, B cells
      together with T cells and dendritic cells form organized nodular aggregates
      surrounded by neo-lymphatic vessels. The functional significance of these
      tertiary lymphoid organs remains to be fully defined. Intrarenal B cells may be
      part of a local system to enhance the immunological response by functioning as
      antigen presenting cells, and as a source for cytokines promoting T-cell
      proliferation and lymphatic neoangiogenesis. In this way, they could enhance the
      local immune response to persisting autoantigens in the tubulointerstitium.

PMID- 18094678
TI  - CDK/GSK-3 inhibitors as therapeutic agents for parenchymal renal diseases.
AB  - Drug discovery to lessen the burden of chronic renal failure and end-stage renal
      disease remains a principle goal of translational research in nephrology. In this
      review, we provide an overview of the current development of small molecule
      cyclin-dependent kinase (CDK)/glycogen synthase kinase-3 (GSK-3) inhibitors as
      therapeutic agents for parenchymal renal diseases. The emergence of this drug
      family has resulted from the recognition that CDKs and GSK-3s play critical roles
      in the progression and regression of many kidney diseases. CDK/GSK-3 inhibitors
      suppress pathogenic proliferation, apoptosis, and inflammation, and promote
      regeneration of injured tissue. Preclinical efficacy has now been demonstrated in
      mesangial proliferative glomerulonephritis, crescentic glomerulonephritis,
      collapsing glomerulopathy, proliferative lupus nephritis, polycystic kidney
      diseases, diabetic nephropathy, and several forms of acute kidney injury. Novel
      biomarkers of therapy are aiding the process of drug development. This review
      will highlight these advancements in renal therapeutics.

PMID- 18094679
TI  - Biomarkers for the diagnosis and risk stratification of acute kidney injury: a
      systematic review.
AB  - The diagnosis of acute kidney injury (AKI) is usually based on changes in serum
      creatinine, but such measurements are a poor marker of acute deterioration in
      kidney function. We performed a systematic review of publications that evaluated
      the accuracy and reliability of serum and urinary biomarkers in human subjects
      when used for the diagnosis of established AKI or early AKI, or to risk stratify
      patients with AKI. Two reviewers independently searched the MEDLINE and EMBASE
      databases (January 2000-March 2007) for studies pertaining to biomarkers for AKI.
      Studies were assessed for methodologic quality. In total, 31 studies evaluated 21
      unique serum and urine biomarkers. Twenty-five of the 31 studies were scored as
      having 'good' quality. The results of the studies indicated that serum cystatin
      C, urine interleukin-18 (IL-18), and urine kidney injury molecule-1 (KIM-1)
      performed best for the differential diagnosis of established AKI. Serum cystatin
      C and urine neutrophil gelatinase-associated lipocalin, IL-18, glutathione-S
      transferase-pi, and gamma-glutathione-S-transferase performed best for early
      diagnosis of AKI. Urine N-acetyl-beta-D-glucosaminidase, KIM-1, and IL-18
      performed the best for mortality risk prediction after AKI. In conclusion,
      published data from studies of serum and urinary biomarkers suggest that
      biomarkers may have great potential to advance the fields of nephrology and
      critical care. These biomarkers need validation in larger studies, and the
      generalizability of biomarkers to different types of AKI as well as the
      incremental prognostic value over traditional clinical variables needs to be
      determined.

PMID- 18094680
TI  - Liver fatty acid-binding protein as a biomarker of acute kidney injury after
      cardiac surgery.
AB  - Acute kidney injury (AKI) is a major complication of cardiac bypass surgery. We
      examined whether levels of liver fatty acid-binding protein (L-FABP) can be an
      early biomarker for ischemic injury by measuring this protein in the urine of 40
      pediatric patients prior to and following cardiopulmonary bypass surgery. AKI was
      defined as a 50% increase in the serum creatinine from baseline, which was
      normally not seen until 24-72 h after surgery. Enzyme-linked immunosorbent assay
      analysis showed increased L-FABP levels (factored for creatinine excretion) of
      about 94- and 45-fold at 4 and 12 h, respectively, following surgery in the 21
      patients who developed AKI with western blot analysis, confirming L-FABP
      identity. Univariate logistic regression analyses showed that both bypass time
      and urinary L-FABP were significant independent risk indicators for AKI. After
      excluding bypass time from the model and using a stepwise multivariate logistic
      regression analysis, urinary L-FABP levels at 4 h after surgery were an
      independent risk indicator with the area under the receiver-operating
      characteristic curve 0.810, sensitivity 0.714, and specificity 0.684 for a 24
      fold increase in urinary L-FABP. Our study shows that urinary L-FABP levels
      represent a sensitive and predictive early biomarker of AKI after cardiac
      surgery.

PMID- 18094681
TI  - Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal
      transformation.
AB  - Aristolochic acid contamination in herbal remedies leads to interstitial
      fibrosis, tubular atrophy, and renal failure in humans. To study the cellular
      mechanisms contributing to the pathophysiology of this renal disease, we studied
      Wistar rats treated with aristolochic acid and measured tubular and interstitial
      cell proliferation, epithelial/mesenchymal cell marker expression, tubular
      membrane integrity, myofibroblast accumulation, oxidative stress, mitochondrial
      damage, tubular apoptosis, and fibrosis. Oxidative stress, a loss of cadherin
      concomitant with vimentin expression, basement membrane denudation with active
      caspase-3 expression, and mitochondrial injury within tubular cells were evident
      within 5 days of administration of the toxin. During the chronic phase,
      interstitial mesenchymal cells accumulated in areas of collagen deposits.
      Impaired regeneration and apoptosis of proximal tubular cells resulted in tubule
      atrophy with a near absence of dedifferentiated cell transmembrane migration. We
      suggest that resident fibroblast activation plays a critical role in the process
      of renal fibrosis during aristolochic acid toxicity.

PMID- 18094682
TI  - A proposed nomenclature and diagnostic criteria for protein-energy wasting in
      acute and chronic kidney disease.
AB  - The recent research findings concerning syndromes of muscle wasting,
      malnutrition, and inflammation in individuals with chronic kidney disease (CKD)
      or acute kidney injury (AKI) have led to a need for new terminology. To address
      this need, the International Society of Renal Nutrition and Metabolism (ISRNM)
      convened an expert panel to review and develop standard terminologies and
      definitions related to wasting, cachexia, malnutrition, and inflammation in CKD
      and AKI. The ISRNM expert panel recommends the term 'protein-energy wasting' for
      loss of body protein mass and fuel reserves. 'Kidney disease wasting' refers to
      the occurrence of protein-energy wasting in CKD or AKI regardless of the cause.
      Cachexia is a severe form of protein-energy wasting that occurs infrequently in
      kidney disease. Protein-energy wasting is diagnosed if three characteristics are
      present (low serum levels of albumin, transthyretin, or cholesterol), reduced
      body mass (low or reduced body or fat mass or weight loss with reduced intake of
      protein and energy), and reduced muscle mass (muscle wasting or sarcopenia,
      reduced mid-arm muscle circumference). The kidney disease wasting is divided into
      two main categories of CKD- and AKI-associated protein-energy wasting. Measures
      of chronic inflammation or other developing tests can be useful clues for the
      existence of protein-energy wasting but do not define protein-energy wasting.
      Clinical staging and potential treatment strategies for protein-energy wasting
      are to be developed in the future.

PMID- 18094683
TI  - Host genome surveillance for retrotransposons by transposon-derived proteins.
AB  - Transposable elements and their remnants constitute a substantial fraction of
      eukaryotic genomes. Host genomes have evolved defence mechanisms, including
      chromatin modifications and RNA interference, to regulate transposable elements.
      Here we describe a genome surveillance mechanism for retrotransposons by
      transposase-derived centromeric protein CENP-B homologues of the fission yeast
      Schizosaccharomyces pombe. CENP-B homologues of S. pombe localize at and recruit
      histone deacetylases to silence Tf2 retrotransposons. CENP-Bs also repress solo
      long terminal repeats (LTRs) and LTR-associated genes. Tf2 elements are clustered
      into 'Tf' bodies, the organization of which depends on CENP-Bs that display
      discrete nuclear structures. Furthermore, CENP-Bs prevent an 'extinct' Tf1
      retrotransposon from re-entering the host genome by blocking its recombination
      with extant Tf2, and silence and immobilize a Tf1 integrant that becomes
      sequestered into Tf bodies. Our results reveal a probable ancient retrotransposon
      surveillance pathway important for host genome integrity, and highlight potential
      conflicts between DNA transposons and retrotransposons, major transposable
      elements believed to have greatly moulded the evolution of genomes.

PMID- 18094684
TI  - Behavioural report of single neuron stimulation in somatosensory cortex.
AB  - Understanding how neural activity in sensory cortices relates to perception is a
      central theme of neuroscience. Action potentials of sensory cortical neurons can
      be strongly correlated to properties of sensory stimuli and reflect the
      subjective judgements of an individual about stimuli. Microstimulation
      experiments have established a direct link from sensory activity to behaviour,
      suggesting that small neuronal populations can influence sensory decisions.
      However, microstimulation does not allow identification and quantification of the
      stimulated cellular elements. The sensory impact of individual cortical neurons
      therefore remains unknown. Here we show that stimulation of single neurons in
      somatosensory cortex affects behavioural responses in a detection task. We
      trained rats to respond to microstimulation of barrel cortex at low current
      intensities. We then initiated short trains of action potentials in single
      neurons by juxtacellular stimulation. Animals responded significantly more often
      in single-cell stimulation trials than in catch trials without stimulation.
      Stimulation effects varied greatly between cells, and on average in 5% of trials
      a response was induced. Whereas stimulation of putative excitatory neurons led to
      weak biases towards responding, stimulation of putative inhibitory neurons led to
      more variable and stronger sensory effects. Reaction times for single-cell
      stimulation were long and variable. Our results demonstrate that single neuron
      activity can cause a change in the animal's detection behaviour, suggesting a
      much sparser cortical code for sensations than previously anticipated.

PMID- 18094685
TI  - Sparse optical microstimulation in barrel cortex drives learned behaviour in
      freely moving mice.
AB  - Electrical microstimulation can establish causal links between the activity of
      groups of neurons and perceptual and cognitive functions. However, the number and
      identities of neurons microstimulated, as well as the number of action potentials
      evoked, are difficult to ascertain. To address these issues we introduced the
      light-gated algal channel channelrhodopsin-2 (ChR2) specifically into a small
      fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2
      photostimulation in vivo reliably generated stimulus-locked action potentials at
      frequencies up to 50 Hz. Here we show that naive mice readily learned to detect
      brief trains of action potentials (five light pulses, 1 ms, 20 Hz). After
      training, mice could detect a photostimulus firing a single action potential in
      approximately 300 neurons. Even fewer neurons (approximately 60) were required
      for longer stimuli (five action potentials, 250 ms). Our results show that
      perceptual decisions and learning can be driven by extremely brief epochs of
      cortical activity in a sparse subset of supragranular cortical pyramidal neurons.

PMID- 18094686
TI  - Routes for drug delivery. Inhalation exposure for small animals serial blood
      collection in mice.

PMID- 18094691
TI  - Replication and the 3Rs: an interesting dialog.

PMID- 18094692
TI  - Replication and the 3Rs.

PMID- 18094693
TI  - Replication and the 3Rs: a word from USDA.

PMID- 18094694
TI  - Replication and the 3Rs: a question of power or an abuse of power?

PMID- 18094695
TI  - Replication and the 3Rs: replication should be independent.

PMID- 18094696
TI  - Sneezing, nasal discharge, dyspnea and sudden death in rabbits.

PMID- 18094697
TI  - Diagnosis | pasteurellosis.

PMID- 18094698
TI  - Microchip placement for identification of birds.
AB  - Individual identification is important for both laboratory and pet birds. This
      column gives instructions for placement of microchips in birds and discusses the
      advantages and disadvantages of this method of identification.

PMID- 18094699
TI  - Comparison of the lateral tail vein and the retro-orbital venous sinus as routes
      of intravenous drug delivery in a transgenic mouse model.
AB  - In mice, intravenous injections are commonly administered in the lateral tail
      vein. This technique is sometimes difficult to carry out and may cause stress to
      mice. Though injection through the retro-orbital venous sinus can provide certain
      advantages over lateral tail vein injection, this method is poorly defined and
      infrequently used. To compare the efficacy of these two routes of drug delivery,
      the authors injected MAFIA transgenic mice with the depletion agent AP20187,
      which selectively induces apoptosis in macrophages. Each mouse received five
      consecutive daily injections through either the lateral tail vein or the retro
      orbital venous sinus. The authors then compared macrophage depletion in different
      tissues (lung, spleen, bone marrow and peritoneal exudate cells). Both routes of
      injection were similarly effective. A separate experiment using BALB/c mice
      indicated that retro-orbital venous sinus injection was the less stressful of the
      two methods.

PMID- 18094700
TI  - Development and use of a single-animal whole-body system for inhalation exposure.
AB  - Inhalation exposure studies, in which test subjects are fully or partially
      immersed in an atmosphere containing a compound of interest, are usually carried
      out using one of two possible exposure systems: large whole-body chambers or
      systems that expose only the animal's nose or head. Whole-body chambers may
      require large quantities of test compound, which can pose a problem if the
      chemical is expensive or available in limited quantities. Nose- or head-only
      systems can help conserve test compound but may cause stress or injury to
      animals. To address these concerns, the authors developed an exposure system
      consisting of small single-animal whole-body chambers. They exposed 80 mice and
      80 rats to five test compounds at various concentrations. Though the system was
      labor-intensive for animal care technicians, it effectively exposed animals to
      precise chemical doses without causing adverse effects, using less test compound
      than would have been required in a conventional whole-body chamber.

PMID- 18094701
TI  - A portal vein cannulation technique for drug discovery in mice.
AB  - One approach to understanding how orally administered drugs are absorbed and
      metabolized involves measuring compound concentrations in portal vein blood and
      in systemic circulation at various time points. In mice, blood samples are
      generally collected through terminal bleeding, a process that requires a large
      number of mice and is susceptible to variation between individuals. The authors
      developed a portal vein cannulation procedure for serial bleeding in the mouse,
      using a modified catheter containing a stainless steel stylet that is implanted
      directly in the portal vein. To demonstrate the technique, they orally
      administered two different compounds to mice and obtained blood samples from the
      tail vein and portal vein at different time points. They analyzed compound
      concentrations using liquid chromatography-tandem mass spectrometry. The
      technique refines existing methods for pharmacokinetic studies in the mouse and
      reduces the number of mice required.

PMID- 18094703
TI  - The effects of dopamine receptor agonists on BK Ca channels and signal
      transduction mechanism in corpus cavernosal smooth muscle cells.
AB  - In this study, we investigated the effect of dopamine receptor agonists on
      potassium channels' activity and their signal transduction pathway in corporal
      smooth muscle cells. We used cultured human corporal smooth muscle cells. The
      whole cell and cell-attached configuration of the patch-clamp technique were used
      for electrophysiological recordings, and enzyme immunoassay was used for
      measuring cyclic AMP (cAMP) and cyclic GMP levels. Extracellular application of
      10 microM dopamine and apomorphine significantly increased whole-cell K(+)
      currents by 283.5+/-55.7% (at +60 mV; n=12, P<0.001), 292.4+/-58.8.0% (at +60 mV;
      n=9, P<0.005), respectively. We confirmed that the increase in whole-cell
      currents was mainly due to activation of the tetraethylammonium-sensitive large
      conductance Ca(2+)-activated K(+) channels (BK(Ca) channels). Enzyme immunoassay
      indicated that dopamine and apomorphine stimulates cAMP levels in corporal smooth
      muscle cells in a concentration-dependent fashion. The activation of BK(Ca)
      channels by dopamine receptor agonists in corporal smooth muscle cells might be
      one of the mechanisms in inducing penile erection.

PMID- 18094704
TI  - NICU lactation consultant increases percentage of outborn versus inborn babies
      receiving human milk.
AB  - OBJECTIVE: To determine the effect of a dedicated lactation consultant (LC) on
      the percentage of neonates receiving any human milk in the neonatal intensive
      care unit (NICU) and at discharge over time. STUDY DESIGN: Retrospective chart
      review of three time periods of 3 months each; Time period 1 (before LC hire),
      Time period 2 (T2; after LC arrival) and Time period 3 (subsequent period after
      T2). RESULT: Percentage of infants receiving any HM during hospital stay and at
      discharge increased significantly over time after LC hire and with LC experience.
      Outborn (OB) infants receiving any HM in the NICU and at discharge increased over
      time, but there was no significant change for inborn infants, as the proportion
      receiving any HM remained consistently high over time. CONCLUSION: Addition of a
      dedicated LC to the NICU increased the percentage of neonates receiving any HM,
      specifically in the OB population.

PMID- 18094705
TI  - Glucose neurotoxicity.
AB  - Neurons have a constantly high glucose demand, and unlike muscle cells they
      cannot accommodate episodic glucose uptake under the influence of insulin.
      Neuronal glucose uptake depends on the extracellular concentration of glucose,
      and cellular damage can ensue after persistent episodes of hyperglycaemia--a
      phenomenon referred to as glucose neurotoxicity. This article reviews the
      pathophysiological manifestation of raised glucose in neurons and how this can
      explain the major components of diabetic neuropathy.

PMID- 18094706
TI  - Be smart, exercise your heart: exercise effects on brain and cognition.
AB  - An emerging body of multidisciplinary literature has documented the beneficial
      influence of physical activity engendered through aerobic exercise on selective
      aspects of brain function. Human and non-human animal studies have shown that
      aerobic exercise can improve a number of aspects of cognition and performance.
      Lack of physical activity, particularly among children in the developed world, is
      one of the major causes of obesity. Exercise might not only help to improve their
      physical health, but might also improve their academic performance. This article
      examines the positive effects of aerobic physical activity on cognition and brain
      function, at the molecular, cellular, systems and behavioural levels. A growing
      number of studies support the idea that physical exercise is a lifestyle factor
      that might lead to increased physical and mental health throughout life.

PMID- 18094707
TI  - Synaptic plasticity, memory and the hippocampus: a neural network approach to
      causality.
AB  - Two facts about the hippocampus have been common currency among neuroscientists
      for several decades. First, lesions of the hippocampus in humans prevent the
      acquisition of new episodic memories; second, activity-dependent synaptic
      plasticity is a prominent feature of hippocampal synapses. Given this background,
      the hypothesis that hippocampus-dependent memory is mediated, at least in part,
      by hippocampal synaptic plasticity has seemed as cogent in theory as it has been
      difficult to prove in practice. Here we argue that the recent development of
      transgenic molecular devices will encourage a shift from mechanistic
      investigations of synaptic plasticity in single neurons towards an analysis of
      how networks of neurons encode and represent memory, and we suggest ways in which
      this might be achieved. In the process, the hypothesis that synaptic plasticity
      is necessary and sufficient for information storage in the brain may finally be
      validated.

PMID- 18094708
TI  - The common variants of E-selectin gene in Graves' disease.
AB  - Adhesion molecules are involved in cell invasion in autoimmune thyroid disease.
      It was also reported that patients with untreated Graves' disease (GD) had high
      serum level of soluble form of E-selectin (sE-selectin), the concentration of
      which correlated with the activity of the disease. The aim of the present study
      was to elucidate whether the common variants in E-selectin gene (SELE) were
      associated with the development of GD. Six tagSNPs within SELE were studied in
      297 patients with GD and 208 healthy subjects in Chinese population. Our data
      showed that common SELE variants were associated with GD (P=0.012-0.036).
      Haplotype analysis of the single nucleotide polymorphisms revealed an association
      of a haplotype ATAACC with GD (P=0.005). Furthermore, quantitative trait analysis
      showed a significant association of SELE haplotype with sE-selectin levels
      (P=0.0438). This study therefore could provide us to a certain degree the insight
      that common SELE variants may be associated with susceptibility to GD in Chinese
      population, though the limitation of sample size and multiple test problems
      exists.

PMID- 18094709
TI  - IRF-3-dependent and augmented target genes during viral infection.
AB  - Activation of the transcription factor interferon regulatory factor-3 (IRF-3) is
      an essential event in the innate immune response to viral infection. To
      understand the contribution of IRF-3 to host defense, we used a systems biology
      approach to analyze global gene expression dependent on IRF-3. Comparison of
      expression profiles in cells from IRF-3 knockout animals or wild-type siblings
      following viral infection revealed three sets of induced genes, those that are
      strictly dependent on IRF-3, augmented with IRF-3, or not responsive to IRF-3.
      Products of identified IRF-3 target genes are involved in innate or acquired
      immunity, or in the regulation of cell cycle, apoptosis and proliferation. These
      results reveal the global effects of one transcription factor in the immune
      response and provide information to evaluate the integrated response to viral
      infection.

PMID- 18094710
TI  - Mhc class I haplotypes associated with survival time in simian immunodeficiency
      virus (SIV)-infected rhesus macaques.
AB  - In both human immunodeficiency virus-infected humans and simian immunodeficiency
      virus (SIV)-infected macaques, genes encoded in the major histocompatibility
      complex (MHC) class I region are important determinants of disease progression.
      However, compared to the human human lymphocyte antigen complex, the macaque MHC
      region encodes many more class I genes. Macaques with the same immunodominant
      class I genes express additional Mhc genes with the potential to influence the
      disease course. We therefore assessed the association between of the Mhc class I
      haplotypes, rather than single gene variants, and survival time in SIV-infected
      rhesus macaques (Macaca mulatta). DNA sequence analysis and Mhc genotyping of 245
      pedigreed monkeys identified 17 Mhc class I haplotypes that constitute 10 major
      genotypes. Among 81 vaccination-naive, SIV-infected macaques, 71 monkeys carried
      at least one Mhc class I haplotype encoding only MHC antigens that were incapable
      of inducing an effective anti-SIV cytotoxic T lymphocytes response. Study of
      these macaques enabled us to relate individual Mhc class I haplotypes to slow,
      medium and rapid disease progression. In a post hoc analysis, classification
      according to disease progression was found to explain at least 48% of the
      observed variation of survival time.

PMID- 18094711
TI  - Prevalence and evolutionary origins of autoimmune susceptibility alleles in
      natural mouse populations.
AB  - The evolutionary origin of genetic diversity in the SLAM/CD2 gene cluster,
      implicated in autoimmune lupus susceptibility in mice, was investigated by
      sequence analysis of exons from six members of the cluster in 48 wild mouse
      samples derived from the global mouse population. A total of 80 coding region
      SNPs were identified among the six genes analyzed, indicating that this gene
      cluster is highly polymorphic in natural mouse populations. Phylogenetic analyses
      of these allelic sequences revealed clustering of alleles derived from multiple
      Mus species and subspecies, indicating alleles at several SLAM/CD2 loci were
      present in ancestral Mus populations prior to speciation and have persisted as
      polymorphisms for more than 1 million years. Analyses of nonsynonymous/synonymous
      ratios using likelihood codon substitution models identified several segments in
      Cd229, Cd48 and Cd84 that were impacted by positive diversifying selective
      pressures. These findings support the interpretation that selection favoring the
      generation and retention of functional polymorphisms has played a role in the
      evolutionary origin of genetic polymorphisms that are predisposing to
      autoimmunity.

PMID- 18094712
TI  - KSHV-transformed primary effusion lymphoma cells induce a VEGF-dependent
      angiogenesis and establish functional gap junctions with endothelial cells.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of primary
      effusion lymphoma (PEL) and of Kaposi's sarcoma. PEL is an aggressive
      proliferation of B cells with poor prognosis. We evaluated both in vitro and in
      vivo the potential role of angiogenic factors secreted by PEL cells, that is,
      their interaction with endothelial cells and their implication in the invasive
      behavior of tumoral cells. In vitro, PEL-induced angiogenesis is dependent on
      vascular endothelial growth factor (VEGF) and VEGF receptors. However, although
      PEL cells produce VEGF and basic fibroblast growth factor (b-FGF) transcripts,
      they only secrete VEGF in vitro. In vivo, very high levels of both VEGF and b-FGF
      were found in the ascitic fluid of NOD/SCID mice injected with PEL cells. We then
      show evidence of cell adhesion and gap junction-mediated heterocellular
      communication between PEL cells and endothelial cells. Finally, we show that PEL
      cells extravasate through the endothelial barrier and that the specific tyrosine
      kinase inhibitor of VEGF receptors, PTK-787/ZK-222584, the anti-VEGF antibody,
      bevacizumab or the gap junction inhibitor 18-alpha-glycyrrhetinic acid, partially
      attenuate PEL cell extravasation. Angiogenesis, cell adhesion and communication
      likely contribute to the development of PEL and represent potential therapeutic
      targets.

PMID- 18094713
TI  - Comparison of hypoplastic myelodysplastic syndrome (MDS) with normo
      /hypercellular MDS by International Prognostic Scoring System, cytogenetic and
      genetic studies.
AB  - The differences in clinical features and prognosis between hypoplastic
      myelodysplastic syndrome (h-MDS) and normo-/hypercellular MDS (NH-MDS) remain
      unsettled. In this study, the characteristics of 37 h-MDS patients and 152 NH-MDS
      patients were compared. Peripheral-blood white blood cell counts and bone marrow
      blast percentage were lower in h-MDS patients than in NH-MDS patients (P=0.012
      and 0.016, respectively). Refractory anemia (RA) was predominant (56.8%) in h
      MDS, whereas RA with excess of blast (RAEB) was most common (44.7%) in NH-MDS.
      Chromosomal abnormalities -7/7q- occurred less frequently in h-MDS patients than
      in NH-MDS patients (0 vs 18.3%, P=0.022). There was no significant difference in
      the prevalence of mutations of RAS, AML1, JAK2, PTPN11, FLT3/ITD, and
      hypermethylation of SOCS1 and SHP1 between these two groups. International
      Prognostic Scoring System (IPSS) was ideal for predicting prognoses in h-MDS
      patients (P=0.002). In low- or intermediate-1 (Int-1)-risk MDS patients, h-MDS
      patients had a superior survival than NH-MDS patients (P=0.01). In conclusion,
      distinct from NH-MDS, h-MDS patients have different patterns of hemogram,
      distribution of French-American-British subtypes, cytogenetic changes and
      prognoses. IPSS is applicable in h-MDS as in NH-MDS. In patients with low- or Int
      1-risk MDS, h-MDS patients have a better prognosis than NH-MDS patients.

PMID- 18094714
TI  - The role of CALM-AF10 gene fusion in acute leukemia.
AB  - Chromosomal translocations are important genetic perturbations frequently
      associated with hematologic malignancies; characterization of these events has
      been a rich source of insights into the mechanisms that lead to malignant
      transformation. The t(10;11)(p13;q14-21) results in a recently identified rare
      but recurring chromosomal translocation seen in patients with ALL as well as AML,
      and results in the production of a CALM-AF10 fusion gene. Although the details by
      which the CALM-AF10 fusion protein exerts its leukemogenic effect remain unclear,
      emerging data suggests that the CALM-AF10 fusion impairs differentiation of
      hematopoietic cells, at least in part via an upregulation of HOXA cluster genes.
      This review discusses the normal structure and function of CALM and AF10,
      describes the spectrum of clinical findings seen in patients with CALM-AF10
      fusions, summarizes recently published CALM-AF10 mouse models and highlights the
      role of HOXA cluster gene activation in CALM-AF10 leukemia.

PMID- 18094715
TI  - Bone marrow fibrosis in childhood acute lymphoblastic leukemia correlates to
      biological factors, treatment response and outcome.
AB  - We retrospectively evaluated reticulin fiber density (RFD) in 166 diagnostic bone
      marrow (BM) biopsies and 62 biopsies obtained at treatment day 29 from children
      with acute lymphoblastic leukemia (ALL). Patients with B-cell precursor (BCP)-ALL
      showed higher RFD as compared to patients with T-cell ALL (P<0.001). RFD
      correlated negatively with white blood cell count (P=0.008) in BCP-ALL patients.
      Patients with high-hyperdiploid ALL (51-61 chromosomes), no high-risk criteria
      and low RFD showed a favorable outcome when compared to similar patients with
      high RFD (P=0.002). In BCP-ALL patients, RFD at diagnosis correlated to the
      levels of minimal residual disease (MRD) analyzed by flow cytometry on treatment
      day 29 (P=0.001). Accordingly, patients with MRD > or = 10(-4) presented higher
      RFD at diagnosis compared to patients with MRD < 10(-4) (P=0.003). BCP-ALL
      patients with low RFD at diagnosis and a rapid reduction of RFD on day 29 had a
      favorable outcome compared to patients with the same baseline RFD level at
      diagnosis but a slow RFD reduction (P=0.041). To our knowledge, these findings
      are novel and may indicate BM fibrosis as a new valuable prognostic marker in
      childhood ALL. Expanded use of BM biopsy both at diagnosis and during follow-up
      is suggested.

PMID- 18094716
TI  - Re-expression of DNA methylation-silenced CD44 gene in a resistant NB4 cell line:
      rescue of CD44-dependent cell death by cAMP.
AB  - In the acute promyelocytic leukemia cell line, NB4, activation of the CD44
      receptor triggers apoptosis. This pathway does not operate in the retinoid
      maturation-resistant NB4-LR1 subclone. In this work, we show that the CD44 gene
      is silenced in these cells. The molecular defect involves DNA methylation of
      cytosine phosphate guanine (CpG) island and underacetylation of histone H3 at
      CD44 promoter. The methylating inhibitor 5-aza-CdR and cyclic AMP (cAMP) reverse
      the CD44 gene silencing. Contrary to 5-aza-CdR, cAMP does not induce DNA
      demethylation or histone modification at the CD44 promoter, whereas an
      H3pS10/AcK14 dual modification is observed on a global level. cAMP also induces
      the expression of c-Jun transcription factor and its recruitment at the CD44
      promoter. Chromatin immunoprecipitation assays further show the association of
      brahma (Brm), a subunit of SWI/SNF chromatin-remodelling complex involved in the
      crosstalk between transcription and RNA polymerase II (RNA Pol II) processing, as
      well as the binding of phosphorylated RNA Pol II to the proximal promoter region
      of CD44. Finally, our study reveals that cAMP re-establishes the CD44-mediated
      cell death signalling. We propose that one of the actions of cAMP in restoring
      normal cell phenotype of leukaemia cells may consist in a broad trans
      reactivation of silenced genes, despite marked hypermethylation of their
      promoters, as illustrated here with CD44 re-expression.

PMID- 18094717
TI  - Immunophenotypic, cytogenetic and functional characterization of circulating
      endothelial cells in myelodysplastic syndromes.
AB  - Circulating endothelial cells (CECs) are associated with neoangiogenesis in
      various malignant disorders. Using flow cytometry, we studied CECs in 128
      patients with myelodysplastic syndrome (MDS). MDS patients had higher CEC levels
      than controls (P<0.001), and an inverse relationship was found between CECs and
      international prognostic scoring system risk (r=-0.55, P<0.001). There was a
      positive correlation between marrow microvessel density and CECs, low-risk
      patients showing the strongest association (r=0.62, P<0.001). We calculated a
      progenitor-to-mature CEC ratio, which was higher in MDS patients than in healthy
      subjects (P<0.001), the highest values were found at diagnosis. CECs assessed by
      flow cytometry positively correlated with the ability to produce endothelial
      colony-forming cells in vitro (ECFCs; r=0.57, P=0.021), which was significantly
      higher in MDS patients than in controls (P=0.011). Fluorescence in situ
      hybridization analysis showed that a variable proportion of CECs (from 40 to 84%)
      carried the same chromosomal aberration as the neoplastic clone, while
      endothelial cells isolated from in vitro assays were negative. This study
      suggests that CECs reflect the abnormal angiogenesis found in MDS, especially in
      the early stages of the disease. The increased number of functional endothelial
      progenitor cells in MDS strengthens the rationale for therapeutic interventions
      aimed at restoring a normal interaction between hematopoietic progenitors and
      marrow microenvironment.

PMID- 18094718
TI  - Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging
      and therapeutic criteria.
AB  - Since the initial description of splenic marginal zone lymphoma (SMZL) in 1992,
      an increasing number of publications have dealt with multiple aspects of SMZL
      diagnosis, molecular pathogenesis and treatment. This process has identified
      multiple inconsistencies in the diagnostic criteria and lack of clear guidelines
      for the staging and treatment. The authors of this review have held several
      meetings and exchanged series of cases with the objective of agreeing on the main
      diagnostic, staging and therapeutic guidelines for patients with this condition.
      Specific working groups were created for diagnostic criteria, immunophenotype,
      staging and treatment. As results of this work, guidelines are proposed for
      diagnosis, differential diagnosis, staging, prognostic factors, treatment and
      response criteria. The guidelines proposed here are intended to contribute to the
      standardization of the diagnosis and treatment of these patients, and should
      facilitate the future development of clinical trials that could define more
      precisely predictive markers for histological progression or lack of response,
      and evaluate new drugs or treatments.

PMID- 18094719
TI  - The role of the proto-oncogene ETS2 in acute megakaryocytic leukemia biology and
      therapy.
AB  - Acute myeloid leukemia (AML) in Down syndrome (DS) children has several unique
      features including a predominance of the acute megakaryocytic leukemia (AMkL)
      phenotype, higher event-free survivals compared to non-DS children using cytosine
      arabinoside (ara-C)/anthracycline-based protocols and a uniform presence of
      somatic mutations in the X-linked transcription factor gene, GATA1. Several
      chromosome 21-localized transcription factor oncogenes including ETS2 may
      contribute to the unique features of DS AMkL. ETS2 transcripts measured by real
      time RT-PCR were 1.8- and 4.1-fold, respectively, higher in DS and non-DS
      megakaryoblasts than those in non-DS myeloblasts. In a doxycycline-inducible
      erythroleukemia cell line, K562pTet-on/ETS2, induction of ETS2 resulted in an
      erythroid to megakaryocytic phenotypic switch independent of GATA1 levels.
      Microarray analysis of doxycycline-induced and doxycycline-uninduced cells
      revealed an upregulation by ETS2 of cytokines (for example, interleukin 1 and
      CSF2) and transcription factors (for example, TAL1), which are key regulators of
      megakaryocytic differentiation. In the K562pTet-on/ETS2 cells, ETS2 induction
      conferred differences in sensitivities to ara-C and daunorubicin, depending on
      GATA1 levels. These results suggest that ETS2 expression is linked to the biology
      of AMkL in both DS and non-DS children, and that ETS2 acts by regulating
      expression of hematopoietic lineage and transcription factor genes involved in
      erythropoiesis and megakaryopoiesis, and in chemotherapy sensitivities.

PMID- 18094720
TI  - Novel antifungal agents as salvage therapy for invasive aspergillosis in patients
      with hematologic malignancies: posaconazole compared with high-dose lipid
      formulations of amphotericin B alone or in combination with caspofungin.
AB  - In patients with hematologic malignancy, invasive aspergillosis continues to be
      associated with high mortality even when treated with conventional antifungal
      therapy. To investigate novel antifungal agents, we compared 53 patients who
      received posaconazole salvage therapy to 52 contemporary control patients who
      received high-dose lipid formulation of amphotericin B (HD-LPD/AMB at > or = 7.5
      mg kg(-1) per day) and 38 other control patients who received caspofungin plus HD
      LPD/AMB. Patients in the three groups had similar. The overall response rate to
      salvage therapy was 40% for posaconazole, 8% for HD-LPD/AMB (P < or = 0.001) and
      11% for combination therapy (P < 0.002). Aspergillosis contributed to the death
      of 40% of posaconazole group, 65% of the HD-LPD/AMB group and 68% of the
      combination group (P < or = 0.008). By multivariate analysis, posaconazole
      therapy independently improved response (9.5; 95% confidence interval, 2.8-32.5;
      P < 0.001). HD-LPD/AMB alone or in combination was associated with a
      significantly higher rate of nephrotoxicity (P < or = 0.02) and hepatotoxicity (P
      < 0.03). In conclusion, posaconazole salvage therapy demonstrated greater
      efficacy and safety than HD-LPD/AMB alone or in combination with caspofungin in
      the salvage therapy of invasive aspergillosis in hematologic malignancy.

PMID- 18094721
TI  - Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma.
AB  - The incidence of venous thromboembolism (VTE) is more than 1 per thousand
      annually in the general population and increases further in cancer patients. The
      risk of VTE is higher in multiple myeloma (MM) patients who receive thalidomide
      or lenalidomide, especially in combination with dexamethasone or chemotherapy.
      Various VTE prophylaxis strategies, such as low-molecular-weight heparin (LMWH),
      warfarin or aspirin, have been investigated in small, uncontrolled clinical
      studies. This manuscript summarizes the available evidence and recommends a
      prophylaxis strategy according to a risk-assessment model. Individual risk
      factors for thrombosis associated with thalidomide/lenalidomide-based therapy
      include age, history of VTE, central venous catheter, comorbidities (infections,
      diabetes, cardiac disease), immobilization, surgery and inherited thrombophilia.
      Myeloma-related risk factors include diagnosis and hyperviscosity. VTE is very
      high in patients who receive high-dose dexamethasone, doxorubicin or multiagent
      chemotherapy in combination with thalidomide or lenalidomide, but not with
      bortezomib. The panel recommends aspirin for patients with < or = 1 risk factor
      for VTE. LMWH (equivalent to enoxaparin 40 mg per day) is recommended for those
      with two or more individual/myeloma-related risk factors. LMWH is also
      recommended for all patients receiving concurrent high-dose dexamethasone or
      doxorubicin. Full-dose warfarin targeting a therapeutic INR of 2-3 is an
      alternative to LMWH, although there are limited data in the literature with this
      strategy. In the absence of clear data from randomized studies as a foundation
      for recommendations, many of the following proposed strategies are the results of
      common sense or derive from the extrapolation of data from many studies not
      specifically designed to answer these questions. Further investigation is needed
      to define the best VTE prophylaxis.

PMID- 18094722
TI  - Methylation analysis of the von Hippel-Lindau gene in acute myeloid leukaemia and
      myelodysplastic syndromes.

PMID- 18094723
TI  - FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division,
      growth and differentiation.
AB  - FBW7 (F-box and WD repeat domain-containing 7) is the substrate recognition
      component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box
      protein)-type ubiquitin ligase. SCF(FBW7) degrades several proto-oncogenes that
      function in cellular growth and division pathways, including MYC, cyclin E, Notch
      and JUN. FBW7 is also a tumour suppressor, the regulatory network of which is
      perturbed in many human malignancies. Numerous cancer-associated mutations in
      FBW7 and its substrates have been identified, and loss of FBW7 function causes
      chromosomal instability and tumorigenesis. This Review focuses on structural and
      functional aspects of FBW7 and its role in the development of cancer.

PMID- 18094724
TI  - The third World Kidney Day: looking back and thinking forward.

PMID- 18094725
TI  - Inherited diseases of the glomerular basement membrane.
AB  - The glomerular basement membrane (GBM) is a specialized form of basement membrane
      that has a major role in the maintenance of the glomerular filtration barrier.
      Like all basement membranes, it contains four main components: type IV collagen,
      laminin, nidogen, and heparan sulfate proteoglycans. Different isoforms of these
      large molecules are produced. These isoforms have a tissue-specific distribution;
      in the mature GBM, the major type IV collagen molecule is the alpha 3 alpha 4
      alpha 5(IV) isoform, associated with laminin-521 (alpha 5 beta2 gamma 1), nidogen
      and agrin heparan sulfate proteoglycans. The importance of the GBM has been
      demonstrated by identification of hereditary glomerular diseases linked to
      structural anomalies of its components; for example, type IV collagen in Alport
      syndrome and familial benign hematuria, and laminin in Pierson syndrome. Type III
      collagen, an interstitial collagen, accumulates within the GBM of patients with
      the nail-patella syndrome, and abnormal deposition of fibronectin, another
      extracellular matrix protein, is characteristic of so-called fibronectin
      nephropathy. Development of animal models of these diseases has facilitated
      precise analysis of pathogenic mechanisms, but no specific treatments are
      available. Therapeutic trials in Alport syndrome nephropathy are underway,
      following promising preliminary results obtained in rodent and canine models of
      the disorder.

PMID- 18094726
TI  - Mechanisms of Disease: the kidney-specific chloride channels ClCKA and ClCKB, the
      Barttin subunit, and their clinical relevance.
AB  - Rodent ClC-K1 and ClC-K2, and their respective human orthologs ClCKA and ClCKB,
      are chloride channels specific to the kidney (and inner ear); Barttin is their
      functionally important subunit. ClC-K1 is predominantly localized to the thin
      ascending limb of the loop of Henle. ClC-K2 is expressed more broadly in the
      distal nephron; expression levels are highest along the thick ascending limb of
      the loop of Henle and distal convoluted tubule. Expression of ClC-K1 is
      upregulated by dehydration and downregulated by the diuretic furosemide, whereas
      expression of ClC-K2 is upregulated by furosemide and downregulated by high salt
      levels. ClCKA is important for maintenance of the corticomedullary osmotic
      gradient and the kidney's capacity to concentrate urine. If its ortholog, ClC-K1,
      is nonfunctional in mice, renal diabetes insipidus develops. ClCKB is a key
      determinant of tubular reabsorption of chloride and electrolytes along the distal
      tubule. A severe salt-losing tubulopathy (Bartter syndrome type III) develops if
      ClCKB is nonfunctional, whereas a common genetic variant of the CLCNKB gene that
      leads to increased activity of ClCKB results in salt-dependent hypertension.
      Disruption of the gene encoding Barttin, BSND, results in a 'double knockout' of
      the functions of both ClCKA and ClCKB, manifesting as Bartter syndrome type IV
      with sensorineural deafness and an especially severe salt-losing phenotype.

PMID- 18094727
TI  - Mechanisms of Disease: erythropoietin resistance in patients with both heart and
      kidney failure.
AB  - Anemia is common in patients who have both heart failure and chronic kidney
      disease, and there is an association between anemia and progression of both
      diseases. The main causes of anemia are deficient production of erythropoietin
      (EPO), iron deficiency, and chronic disease with endogenous EPO resistance. EPO
      has been successfully used for over a decade to treat anemia in patients with
      chronic kidney disease. Less obvious are the safety and efficacy of EPO treatment
      in patients with both heart failure and renal disease. Up to 10% of patients
      receiving EPO are hyporesponsive to therapy and require large doses of the agent.
      Several mechanisms could explain resistance to endogenous and exogenous EPO.
      Proinflammatory cytokines antagonize the action of EPO by exerting an inhibitory
      effect on erythroid progenitor cells and by disrupting iron metabolism (a process
      in which hepcidin has a central role). EPO resistance might also be caused by
      inflammation, which has a negative effect on EPO receptors. Furthermore,
      neocytolysis could have a role. As resistance to exogenous EPO is associated with
      an increased risk of death, it is important to understand how cardiorenal failure
      affects EPO production and function.

PMID- 18094728
TI  - Prevalent and low-frequency null mutations in the filaggrin gene are associated
      with early-onset and persistent atopic eczema.

PMID- 18094729
TI  - Single-nucleotide polymorphisms and haplotypes in the VEGF receptor 3 gene and
      the haplotype GC in the VEGFA gene are associated with psoriasis in Koreans.

PMID- 18094730
TI  - Normophosphatemic familial tumoral calcinosis is caused by deleterious mutations
      in SAMD9, encoding a TNF-alpha responsive protein.
AB  - Normophosphatemic familial tumoral calcinosis (NFTC) is an autosomal recessive
      disorder characterized by calcium deposition in skin and mucosae and associated
      with unremitting pain and life-threatening skin infections. A homozygous missense
      mutation (p.K1495E), resulting in SAMD9 protein degradation, was recently shown
      to cause NFTC in five families of Jewish-Yemenite origin. In this study, we
      evaluated another Jewish-Yemenite NFTC kindred. All patients were compound
      heterozygous for two mutations in SAMD9: K1495E and a previously unreported
      nonsense mutation, R344X, predicted to result in a markedly truncated molecule.
      Screening of unaffected population-matched controls revealed heterozygosity for
      K1495E and R344X only in individuals of Jewish-Yemenite ancestry, but not in more
      than 700 control samples of other origins, including 93 non-Jewish Yemenite.
      These data may be suggestive of positive selection, considering the rarity of
      NFTC and the small size of the Jewish-Yemenite population; alternatively, they
      may reflect genetic drift or the effect of a population-specific modifier trait.
      Calcifications in NFTC generally develop over areas subjected to repeated trauma
      and are associated with marked inflammatory manifestations, indicating that SAMD9
      may play a role in the inflammatory response to tissue injury. We therefore
      assessed the effect of cellular stress and tumor necrosis factor-alpha (TNF
      alpha), a potent pro-inflammatory cytokine, on SAMD9 gene expression. Whereas
      exogenous hydrogen peroxide and heat shock did not affect SAMD9 transcription,
      osmotic shock was found to markedly upregulate SAMD9 expression. In addition,
      incubation of endothelial cells with TNF-alpha caused a dose-related, p38
      dependant increase in SAMD9 expression. These data link NFTC and SAMD9 to the TNF
      alpha signaling pathway, suggesting a role for this system in the regulation of
      extra-osseous calcification.

PMID- 18094731
TI  - Cells isolated from the epidermis by Hoechst dye exclusion, small size, and
      negative selection for hematopoietic markers can generate B lymphocyte
      precursors.
AB  - Transdifferentiation has become a common claim for somatic stem cells, yet how
      such cells can be directed toward a specified cell lineage has not been well
      investigated. We previously demonstrated that when isolated epidermal stem cells
      were placed into an embryonic environment, their potential was extended beyond
      the keratinocyte lineage. Here, we present evidence that cells isolated using a
      modification of our published method for epidermal stem cells can be specifically
      directed to differentiate into B lymphocyte precursors. We found that these
      isolated cells co-cultured with S17 bone marrow stromal cells in cytokine
      supplemented medium changed their cell surface marker profile and gene expression
      pattern to one characteristic of B lymphocyte precursors. Such cells also
      underwent variable, diversity, joining rearrangement at the immunoglobulin heavy
      chain locus, a permanent genetic change unique to lymphocytes. This feature is
      limited to the cells isolated using the modified epidermal stem cell method, as
      cells isolated using the modified transit amplifying cell method could not be re
      directed or reprogrammed. Such results demonstrate that cells from the epidermis
      can be directed to cross lineage boundaries to become mesodermally derived
      lymphocytes.

PMID- 18094732
TI  - Impact of homozygosity of R151C variant of MC1r in human hair follicle
      melanocytes.

PMID- 18094735
TI  - Acute liver failure.

PMID- 18094733
TI  - Complex hair cycle domain patterns and regenerative hair waves in living rodents.
AB  - Single hair follicles go through regeneration and involution cycles. In a
      population, hair follicles may affect each other during anagen re-entry, thus
      forming propagating regenerative hair waves. We review these regenerative hair
      waves and complex hair cycle domains, which were recently reported in transgenic
      mice. Two non-invasive methods to track the propagating hair wave in large
      populations of hair follicles in vivo are described. We also reviewed early
      accounts of "hair growth patterns" from classical literature. We decipher the
      "behavior rules" that dictate how dynamic hair waves lead to complex hair cycle
      domains. In general, a single domain expands when a regenerative hair wave
      reaches a responsive region and boundaries form when the wave reaches a non
      responsive region. As mice age, multiple hair cycle domains form, each with its
      own regeneration rhythm. Domain patterns can be reset by physiological events
      such as pregnancy and lactation. Longitudinal sections across domains show arrays
      of follicles in a continuum of hair cycle stages. Hair cycle domains are
      different from regional specificity domains. Regenerative hair waves are
      different from the developmental wave of newly forming hair follicles. The study
      provides insights into the dynamic states of adult skin and physiological
      regulation of organ regeneration.

PMID- 18094736
TI  - A rare case of juvenile fibrosarcoma of eyelid.
AB  - Juvenile fibrosarcoma is not an uncommon tumor in children; however, eyelid
      involvement is extremely rare. Very few cases have been reported in the
      literature. This is the first case of JFS of the eyelid in Tribhuvan University
      Teaching Hospital and the first diagnosed case in Nepal. Histologically, it is
      similar to adult fibrosarcoma but it has an excellent prognosis. Surgical
      excision is the mainstay of treatment; however chemotherapy has been proved
      effective. Here we present a case of juvenile fibrosarcoma of the eyelid in a
      four year female child presenting with a rapidly enlarging, painless, left upper
      eyelid mass. An incisional biopsy, from the eyelid mass, showed typical
      histopathological features of juvenile fibrosarcoma.

PMID- 18094737
TI  - Low birth weight at term: relationship with maternal anthropometry.
AB  - The objective of this study was to determine the relationship of maternal
      anthropometry with low birth weight at term. This study was conducted at the
      Maternity Hospital, Thapathali, from 6th December 2004 to 30th January 2005. It
      was a prospective, hospital based, comparative study, carried out in 308 women
      who had delivered singleton live babies at term. The study population was divided
      into two groups based on baby's weight. During the study period, 154 women, who
      had delivered term low birth weight (LBW) babies (<2500gm), were taken as cases.
      For each case, a comparative case (matching in age and parity) who had delivered
      normal birth weight (NBW) baby (2500gm) was selected and served as control.
      Maternal anthropometric measurements were compared between the two groups. The
      variables studied were post-delivery maternal weight, height, body mass index
      (BMI) and mid upper arm circumference (MUAC). The incidence of low birth weight
      during the study period was 12.76% (329 of 2577 total births). The incidence of
      term low birth weight was 8.15% among the 2283 term births. In mothers with low
      weight (<45.0kg), low birth weight babies were three times more common than in
      mothers with normal weight (OR 3.5 95% CI 1.82-6.77) and with low MUAC (<22.0cm),
      it was twice as common (OR 2.04 95% CI 1.14-3.63). In mothers with low height
      (<145.0cm), LBW babies were higher but could not reach significant level (OR 1.87
      95% CI 0.98-3.75). Similarly, in mothers with low BMI (<18.5kg/m2), the
      difference was not significant (OR 1.9 95%CI 0.61-5.65). On multiple logistic
      regression analysis, only low maternal weight was powerful enough to remain
      significant (OR 2.84 95% CI 1.34-5.99). From these results, it can be concluded
      that low maternal anthropometric measurements have a definite role in causing LBW
      babies at term. Among the studied variables, maternal weight showed the strongest
      influence on low birth weight.

PMID- 18094738
TI  - Indirect traumatic optic neuropathy--retrospective interventional case series
      from a tertiary care center in eastern Nepal.
AB  - To report the demography, nature of insult and ocular characteristics in patients
      presenting with indirect traumatic optic neuropathy and to evaluate the visual
      outcome with mega dose methylprednisolone therapy. Retrospective hospital data
      analysis of all patients admitted with indirect traumatic optic neuropathy and
      treated with mega dose methylprednisolone therapy in the last three years was
      conducted. Nine patients (M:F= 8:1) were identified with unilateral optic nerve
      injury. Road traffic injury was the most common cause of injury. Lid ecchymosis
      and swelling on the same side was the most frequent ocular abnormality noted,
      followed by loss of consciousness. Time of presentation varied from 3 hours to 11
      days. All patients except two had visual acuity of no light perception at
      presentation. Following therapy there was improvement in visual acuity in two
      patients who presented within two days of injury. Patients present late with
      traumatic optic neuropathy in this hospital. Most of the patients are with no
      light perception. High dose steroids was found to be beneficial only in patients
      presenting early (<two days).

PMID- 18094739
TI  - A five year review of clinical profile in HSP.
AB  - To study the clinical profile of Henoch Schonlein Purpura [HSP] in children. A
      retrospective case series of 30 consecutive children with a diagnosis of HSP,
      with special focus on clinical manifestations. Two cases with unusual features
      are described in detail. Data of 19 boys and 11 girls with a mean age of 10.55
      years was reviewed. Overall skin was involved in 100%, joints in 86.7%, GIT in
      80% and renal system in 30% Two-thirds had palpable purpura at presentation. The
      mean duration of appearance of skin lesions after preceding joint and
      gastrointestinal symptoms was 8.6 days and 6.6 days respectively. Abdominal pain
      was the most common gastrointestinal symptom. Knee and ankle involvement occurred
      in more than 3/4th of the patients with arthritis. Vesciculobullous lesions were
      seen in two patients while one patient had rheumatic fever. Most children with
      HSP will have classical manifestation of the disease but diagnostic confusion can
      occur in those with atypical or absent cutaneous features at the onset.

PMID- 18094740
TI  - Differentials of post-partum amenorrhea: a survival analysis.
AB  - Post-partum amenorrhea is an important event for females' reproductive life and
      their health. It is the time period between the end of pregnancy and the
      resumption of menstruation after delivery, and it is considered to be the
      temporary infecundable period of women's reproductive life-span. The main aim of
      this article is to examine the differentials of post-partum amenorrhea by using
      current status reporting data according to the characteristics of the mother and
      her child. The data are utilized from a sample survey of Palpa and Rupandehi
      districts of western rural Nepal. A life-table based technique of survival
      analysis has been used. Important summary measures have been computed in order to
      see the differentials of duration of post-partum amenorrhea. The study revealed
      that parity of mothers, age of mothers, breast-feeding practices and survival
      status of the child were found to be the main differentials of the duration of
      post-partum amenorrhea. Amenorrhea period was found shorter for lower parity and
      younger mothers. Amenorrheic period was found to be increased with increased
      birth-interval and duration of breast-feeding practices. A strong positive
      association was found between the duration of post-partum amenorrhea and breast
      feeding. The study also revealed that an inverse association was found between
      the duration of post-partum amenorrhea and socio-economic status of mothers. The
      survival status of the child showed a strong effect for the timing of amenorrhea.
      This study investigated the important differentials of amenorrhea by using
      current status reporting data according to the characteristics of mother and her
      child. The estimated values of mean, median and trimean duration of amenorrhea
      were compared. For instance, trimean of amenorrheic period was found to be 9.6
      months while median was 8.4 months and mean was 10.4 months. This finding
      indicates that the trimean provided the most consistent and best estimates of the
      duration of amenorrhea than other averages. The trimean is the best measure if
      the data contain censored and open-ended class interval. Parity, age of mothers,
      survival status of child, breast-feeding practices and socio-economic status of
      mothers were found to be the main influencing factors for the timing of
      amenorrhea among rural Nepalese mothers. Although the coverage of the present
      study is limited to small areas as well as to a small sample size, it is expected
      that the findings may help in designing appropriate policies and programs for
      improving mothers' and children's health as well as for reducing the existing
      fertility level of a country.

PMID- 18094741
TI  - Acute liver failure caused by hepatitis E virus and paracetamol.
AB  - Acute liver failure is characterized by severe and sudden liver cell dysfunction
      leading to hepatic encephalopathy and hepatic coagulopathy in a person without
      history of liver disease in the past. This catastrophic illness can rapidly
      progress to coma and death from cerebral edema and multi organ dysfunction. It
      carries a high mortality rate if liver transplantation is not carried out. In
      West, paracetamol is the main cause of hepatotoxicity whereas in the East viral
      hepatitis tops the list. This report describes a case of acute liver failure in
      which probably both the agents were involved. The patient recovered with antidote
      therapy and maximum supportive care.

PMID- 18094742
TI  - Combined epidural anesthesia & general anesthesia for aorto-renal bypass: two
      case reports.
AB  - Aorto-renal bypass surgery is associated with significant hemodynamic alterations
      as well as other comorbidities due to necessity of aortic cross-clamping and
      release during vascular anastomosis. Combined epidural and general anesthesia for
      the aorto-renal bypass surgeries provides not only hemodynamic stability during
      aortic cross-clamping but is also associated with increased graft blood flow,
      graft survival and decreased morbidity and mortality in intraoperative and
      postoperative period. Two cases of aorto-renal bypass are presented, for which
      combined epidural and general anesthesia techniques were applied.

PMID- 18094743
TI  - Relapsing polychondritis: a rare disease of multisystem involvement.
AB  - Relapsing Polychondritis (RP) is a rare connective tissue disease of unclear
      pathogenesis and may present with multisystem involvement. In this report we
      describe a case of Relapsing Polychondritis, a rare autoimmune disease of varied
      presentation, course, and response to therapy.

PMID- 18094744
TI  - Patient information leaflets in surgical practice: a contemporary review.
AB  - Undergoing any surgical procedure, however minor this may be, generates a certain
      degree of anxiety amongst the patients, which is primarily related to the
      possible postoperative course and complications. Introduction of Patient
      Information Leaflets (PIL) in routine surgical practice has helped ameliorate
      this problem significantly and therefore has become a standard practice in the
      United Kingdom and elsewhere. This review highlights the evidence available in
      support of the use of PIL and outlines the process of development of PIL in
      surgical practice.

PMID- 18094745
TI  - Knowledge about human genetics among school students of eastern Nepal.
AB  - School students from 10 to 19 years of age are adolescents. Adolescent girls are
      usually exposed to consequences of early marriage, pregnancy and increased
      responsibility. Genetic disorders are important issues to persons of the
      reproductive age group. History-taking and screening-tests could uncover risk
      factors that require diagnostic testing during pregnancy. Therefore, the present
      survey was conducted among 707 school students (55.6% males, 44.4% females) to
      find out their knowledge about human genetics. Data were collected as written
      responses to a close-ended questionnaire. The knowledge of students about human
      genetic was found to be poor. The majority of students was not aware of the
      prevalence of genetic disorders in the community. Many students (75%) felt that
      genetic laboratory facilities and counseling services are necessary in this
      country. More than half of the students did not know the name of a hospital where
      genetic laboratory services are available. The study indicates that there is a
      need to introduce the basics of human genetics in the school curriculum and to
      implement strategies for awareness programs about genetic disorders and their
      early detection for possible intervention.

PMID- 18094746
TI  - An overview of fast convergent ordered-subsets reconstruction methods for
      emission tomography based on the incremental EM algorithm.
AB  - Statistical reconstruction has become popular in emission computed tomography but
      suffers slow convergence (to the MAP or ML solution). Methods proposed to address
      this problem include the fast but non-convergent OSEM and the convergent RAMLA
      [1] for the ML case, and the convergent BSREM [2], relaxed OS-SPS and modified
      BSREM [3] for the MAP case. The convergent algorithms required a user-determined
      relaxation schedule. We proposed fast convergent OS reconstruction algorithms for
      both ML and MAP cases, called COSEM (Complete-data OSEM), which avoid the use of
      a relaxation schedule while maintaining convergence. COSEM is a form of
      incremental EM algorithm. Here, we provide a derivation of our COSEM algorithms
      and demonstrate COSEM using simulations. At early iterations, COSEM-ML is
      typically slower than RAMLA, and COSEM-MAP is typically slower than optimized
      BSREM while remaining much faster than conventional MAP-EM. We discuss how COSEM
      may be modified to overcome these limitations.

PMID- 18094747
TI  - A systems biology approach identifies a R2R3 MYB gene subfamily with distinct and
      overlapping functions in regulation of aliphatic glucosinolates.
AB  - BACKGROUND: Glucosinolates are natural metabolites in the order Brassicales that
      defend plants against both herbivores and pathogens and can attract specialized
      insects. Knowledge about the genes controlling glucosinolate regulation is
      limited. Here, we identify three R2R3 MYB transcription factors regulating
      aliphatic glucosinolate biosynthesis in Arabidopsis by combining several systems
      biology tools. METHODOLOGY/PRINCIPAL FINDINGS: MYB28 was identified as a
      candidate regulator of aliphatic glucosinolates based on its co-localization
      within a genomic region controlling variation both in aliphatic glucosinolate
      content (metabolite QTL) and in transcript level for genes involved in the
      biosynthesis of aliphatic glucosinolates (expression QTL), as well as its co
      expression with genes in aliphatic glucosinolate biosynthesis. A phylogenetic
      analysis with the R2R3 motif of MYB28 showed that it and two homologues, MYB29
      and MYB76, were members of an Arabidopsis-specific clade that included three
      characterized regulators of indole glucosinolates. Over-expression of the
      individual MYB genes showed that they all had the capacity to increase the
      production of aliphatic glucosinolates in leaves and seeds and induce gene
      expression of aliphatic biosynthetic genes within leaves. Analysis of leaves and
      seeds of single knockout mutants showed that mutants of MYB29 and MYB76 have
      reductions in only short-chained aliphatic glucosinolates whereas a mutant in
      MYB28 has reductions in both short- and long-chained aliphatic glucosinolates.
      Furthermore, analysis of a double knockout in MYB28 and MYB29 identified an
      emergent property of the system since the absence of aliphatic glucosinolates in
      these plants could not be predicted by the chemotype of the single knockouts.
      CONCLUSIONS/SIGNIFICANCE: It seems that these cruciferous-specific MYB regulatory
      genes have evolved both overlapping and specific regulatory capacities. This
      provides a unique system within which to study the evolution of MYB regulatory
      factors and their downstream targets.

PMID- 18094748
TI  - Perceptual learning in the absence of task or stimulus specificity.
AB  - Performance on most sensory tasks improves with practice. When making
      particularly challenging sensory judgments, perceptual improvements in
      performance are tightly coupled to the trained task and stimulus configuration.
      The form of this specificity is believed to provide a strong indication of which
      neurons are solving the task or encoding the learned stimulus. Here we
      systematically decouple task- and stimulus-mediated components of trained
      improvements in perceptual performance and show that neither provides an adequate
      description of the learning process. Twenty-four human subjects trained on a
      unique combination of task (three-element alignment or bisection) and stimulus
      configuration (vertical or horizontal orientation). Before and after training, we
      measured subjects' performance on all four task-configuration combinations. What
      we demonstrate for the first time is that learning does actually transfer across
      both task and configuration provided there is a common spatial axis to the
      judgment. The critical factor underlying the transfer of learning effects is not
      the task or stimulus arrangements themselves, but rather the recruitment of
      commons sets of neurons most informative for making each perceptual judgment.

PMID- 18094750
TI  - Bub1 is a fission yeast kinetochore scaffold protein, and is sufficient to
      recruit other spindle checkpoint proteins to ectopic sites on chromosomes.
AB  - The spindle checkpoint delays anaphase onset until all chromosomes have attached
      in a bi-polar manner to the mitotic spindle. Mad and Bub proteins are recruited
      to unattached kinetochores, and generate diffusible anaphase inhibitors.
      Checkpoint models propose that Mad1 and Bub1 act as stable kinetochore-bound
      scaffolds, to enhance recruitment of Mad2 and Mad3/BubR1, but this remains
      untested for Bub1. Here, fission yeast FRAP experiments confirm that Bub1 stably
      binds kinetochores, and by tethering Bub1 to telomeres we demonstrate that it is
      sufficient to recruit anaphase inhibitors in a kinase-independent manner. We
      propose that the major checkpoint role for Bub1 is as a signalling scaffold.

PMID- 18094749
TI  - A high quality draft consensus sequence of the genome of a heterozygous grapevine
      variety.
AB  - BACKGROUND: Worldwide, grapes and their derived products have a large market. The
      cultivated grape species Vitis vinifera has potential to become a model for fruit
      trees genetics. Like many plant species, it is highly heterozygous, which is an
      additional challenge to modern whole genome shotgun sequencing. In this paper a
      high quality draft genome sequence of a cultivated clone of V. vinifera Pinot
      Noir is presented. PRINCIPAL FINDINGS: We estimate the genome size of V. vinifera
      to be 504.6 Mb. Genomic sequences corresponding to 477.1 Mb were assembled in
      2,093 metacontigs and 435.1 Mb were anchored to the 19 linkage groups (LGs). The
      number of predicted genes is 29,585, of which 96.1% were assigned to LGs. This
      assembly of the grape genome provides candidate genes implicated in traits
      relevant to grapevine cultivation, such as those influencing wine quality, via
      secondary metabolites, and those connected with the extreme susceptibility of
      grape to pathogens. Single nucleotide polymorphism (SNP) distribution was
      consistent with a diffuse haplotype structure across the genome. Of around
      2,000,000 SNPs, 1,751,176 were mapped to chromosomes and one or more of them were
      identified in 86.7% of anchored genes. The relative age of grape duplicated genes
      was estimated and this made possible to reveal a relatively recent Vitis-specific
      large scale duplication event concerning at least 10 chromosomes (duplication not
      reported before). CONCLUSIONS: Sanger shotgun sequencing and highly efficient
      sequencing by synthesis (SBS), together with dedicated assembly programs,
      resolved a complex heterozygous genome. A consensus sequence of the genome and a
      set of mapped marker loci were generated. Homologous chromosomes of Pinot Noir
      differ by 11.2% of their DNA (hemizygous DNA plus chromosomal gaps). SNP markers
      are offered as a tool with the potential of introducing a new era in the
      molecular breeding of grape.

PMID- 18094751
TI  - Thiacetazone, an antitubercular drug that inhibits cyclopropanation of cell wall
      mycolic acids in mycobacteria.
AB  - BACKGROUND: Mycolic acids are a complex mixture of branched, long-chain fatty
      acids, representing key components of the highly hydrophobic mycobacterial cell
      wall. Pathogenic mycobacteria carry mycolic acid sub-types that contain
      cyclopropane rings. Double bonds at specific sites on mycolic acid precursors are
      modified by the action of cyclopropane mycolic acid synthases (CMASs). The latter
      belong to a family of S-adenosyl-methionine-dependent methyl transferases, of
      which several have been well studied in Mycobacterium tuberculosis, namely, MmaA1
      through A4, PcaA and CmaA2. Cyclopropanated mycolic acids are key factors
      participating in cell envelope permeability, host immunomodulation and
      persistence of M. tuberculosis. While several antitubercular agents inhibit
      mycolic acid synthesis, to date, the CMASs have not been shown to be drug
      targets. METHODOLOGY/PRINCIPLE FINDINGS: We have employed various complementary
      approaches to show that the antitubercular drug, thiacetazone (TAC), and its
      chemical analogues, inhibit mycolic acid cyclopropanation. Dramatic changes in
      the content and ratio of mycolic acids in the vaccine strain Mycobacterium bovis
      BCG, as well as in the related pathogenic species Mycobacterium marinum were
      observed after treatment with the drugs. Combination of thin layer
      chromatography, mass spectrometry and Nuclear Magnetic Resonance (NMR) analyses
      of mycolic acids purified from drug-treated mycobacteria showed a significant
      loss of cyclopropanation in both the alpha- and oxygenated mycolate sub-types.
      Additionally, High-Resolution Magic Angle Spinning (HR-MAS) NMR analyses on whole
      cells was used to detect cell wall-associated mycolates and to quantify the
      cyclopropanation status of the cell envelope. Further, overexpression of cmaA2,
      mmaA2 or pcaA in mycobacteria partially reversed the effects of TAC and its
      analogue on mycolic acid cyclopropanation, suggesting that the drugs act directly
      on CMASs. CONCLUSIONS/SIGNIFICANCE: This is a first report on the mechanism of
      action of TAC, demonstrating the CMASs as its cellular targets in mycobacteria.
      The implications of this study may be important for the design of alternative
      strategies for tuberculosis treatment.

PMID- 18094752
TI  - Adipose gene expression prior to weight loss can differentiate and weakly predict
      dietary responders.
AB  - BACKGROUND: The ability to identify obese individuals who will successfully lose
      weight in response to dietary intervention will revolutionize disease management.
      Therefore, we asked whether it is possible to identify subjects who will lose
      weight during dietary intervention using only a single gene expression snapshot.
      METHODOLOGY/PRINCIPAL FINDINGS: The present study involved 54 female subjects
      from the Nutrient-Gene Interactions in Human Obesity-Implications for Dietary
      Guidelines (NUGENOB) trial to determine whether subcutaneous adipose tissue gene
      expression could be used to predict weight loss prior to the 10-week consumption
      of a low-fat hypocaloric diet. Using several statistical tests revealed that the
      gene expression profiles of responders (8-12 kgs weight loss) could always be
      differentiated from non-responders (<4 kgs weight loss). We also assessed whether
      this differentiation was sufficient for prediction. Using a bottom-up (i.e. black
      box) approach, standard class prediction algorithms were able to predict dietary
      responders with up to 61.1%+/-8.1% accuracy. Using a top-down approach (i.e.
      using differentially expressed genes to build a classifier) improved prediction
      accuracy to 80.9%+/-2.2%. CONCLUSION: Adipose gene expression profiling prior to
      the consumption of a low-fat diet is able to differentiate responders from non
      responders as well as serve as a weak predictor of subjects destined to lose
      weight. While the degree of prediction accuracy currently achieved with a gene
      expression snapshot is perhaps insufficient for clinical use, this work reveals
      that the comprehensive molecular signature of adipose tissue paves the way for
      the future of personalized nutrition.

PMID- 18094755
TI  - Predicting the future.

PMID- 18094753
TI  - Multi-locus sequence typing of Bartonella henselae isolates from three continents
      reveals hypervirulent and feline-associated clones.
AB  - Bartonella henselae is a zoonotic pathogen and the causative agent of cat scratch
      disease and a variety of other disease manifestations in humans. Previous
      investigations have suggested that a limited subset of B. henselae isolates may
      be associated with human disease. In the present study, 182 human and feline B.
      henselae isolates from Europe, North America and Australia were analysed by multi
      locus sequence typing (MLST) to detect any associations between sequence type
      (ST), host species and geographical distribution of the isolates. A total of 14
      sequence types were detected, but over 66% (16/24) of the isolates recovered from
      human disease corresponded to a single genotype, ST1, and this type was detected
      in all three continents. In contrast, 27.2% (43/158) of the feline isolates
      corresponded to ST7, but this ST was not recovered from humans and was restricted
      to Europe. The difference in host association of STs 1 (human) and 7 (feline) was
      statistically significant (P< or =0.001). eBURST analysis assigned the 14 STs to
      three clonal lineages, which contained two or more STs, and a singleton
      comprising ST7. These groups were broadly consistent with a neighbour-joining
      tree, although splits decomposition analysis was indicative of a history of
      recombination. These data indicate that B. henselae lineages differ in their
      virulence properties for humans and contribute to a better understanding of the
      population structure of B. henselae.

PMID- 18094754
TI  - Linking gene expression and functional network data in human heart failure.
AB  - BACKGROUND: Gene expression profiling and the analysis of protein-protein
      interaction (PPI) networks may support the identification of disease bio-markers
      and potential drug targets. Thus, a step forward in the development of systems
      approaches to medicine is the integrative analysis of these data sources in
      specific pathological conditions. We report such an integrative bioinformatics
      analysis in human heart failure (HF). A global PPI network in HF was assembled,
      which by itself represents a useful compendium of the current status of human HF
      relevant interactions. This provided the basis for the analysis of interaction
      connectivity patterns in relation to a HF gene expression data set. RESULTS:
      Relationships between the significance of the differentiation of gene expression
      and connectivity degrees in the PPI network were established. In addition,
      relationships between gene co-expression and PPI network connectivity were
      analysed. Highly-connected proteins are not necessarily encoded by genes
      significantly differentially expressed. Genes that are not significantly
      differentially expressed may encode proteins that exhibit diverse network
      connectivity patterns. Furthermore, genes that were not defined as significantly
      differentially expressed may encode proteins with many interacting partners.
      Genes encoding network hubs may exhibit weak co-expression with the genes
      encoding their interacting protein partners. We also found that hubs and
      superhubs display a significant diversity of co-expression patterns in comparison
      to peripheral nodes. Gene Ontology (GO) analysis established that highly
      connected proteins are likely to be engaged in higher level GO biological process
      terms, while low-connectivity proteins tend to be engaged in more specific
      disease-related processes. CONCLUSION: This investigation supports the hypothesis
      that the integrative analysis of differential gene expression and PPI network
      analysis may facilitate a better understanding of functional roles and the
      identification of potential drug targets in human heart failure.

PMID- 18094758
TI  - How to exploit the features of microfluidics technology.

PMID- 18094759
TI  - Molecular sieving using nanofilters: past, present and future.
AB  - Filtration of molecules by nanometer-sized structures is ubiquitous in our
      everyday life, but our understanding of such molecular filtration processes is
      far less than desired. Until recently, one of the main reasons was the lack of
      experimental methods that can help provide detailed, microscopic pictures of
      molecule-nanostructure interactions. Several innovations in experimental methods,
      such as nuclear track-etched membranes developed in the 70s, and more recent
      development of nanofluidic molecular filters, played pivotal roles in advancing
      our understanding. With the ability to make truly molecular-scale filters and
      pores with well-defined sizes, shapes, and surface properties, now we are well
      positioned to engineer better functionality in molecular sieving, separation and
      other membrane applications. Reviewing past theoretical developments (often
      scattered across different fields) and connecting them to the most recent
      advances in the field would be essential to get a full, unified view on this
      important engineering question.

PMID- 18094760
TI  - Biomolecular gradients in cell culture systems.
AB  - Biomolecule gradients have been shown to play roles in a wide range of biological
      processes including development, inflammation, wound healing, and cancer
      metastasis. Elucidation of these phenomena requires the ability to expose cells
      to biomolecule gradients that are quantifiable, controllable, and mimic those
      that are present in vivo. Here we review the major biological phenomena in which
      biomolecule gradients are employed, traditional in vitro gradient-generating
      methods developed over the past 50 years, and new microfluidic devices for
      generating gradients. Microfluidic gradient generators offer greater levels of
      precision, quantitation, and spatiotemporal gradient control than traditional
      methods, and may greatly enhance our understanding of many biological phenomena.
      For each method, we outline the salient features, capabilities, and applications.

PMID- 18094761
TI  - Demonstration of a bio-microactuator powered by vascular smooth muscle cells
      coupled to polymer micropillars.
AB  - We have demonstrated the working principle of a bio-microactuator using smooth
      muscle cells (SMCs) by driving micropillars coupled to cultured SMCs and
      controlled pillar displacements by chemical stimuli; the generated driving force
      was estimated to be over 1.1 microN.

PMID- 18094762
TI  - Gene transfer and protein dynamics in stem cells using single cell
      electroporation in a microfluidic device.
AB  - There is great interest in genetic modification of bone marrow-derived
      mesenchymal stem cells (MSC), not only for research purposes but also for use in
      (autologous) patient-derived-patient-used transplantations. A major drawback of
      bulk methods for genetic modifications of (stem) cells, like bulk
      electroporation, is its limited yield of DNA transfection (typically then 10%).
      This is even more limited when cells are present at very low numbers, as is the
      case for stem cells. Here we present an alternative technology to transfect cells
      with high efficiency (>75%), based on single cell electroporation in a
      microfluidic device. In a first experiment we show that we can successfully
      transport propidium iodide (PI) into single mouse myoblastic C2C12 cells.
      Subsequently, we show the use of this microfluidic device to perform successful
      electroporation of single mouse myoblastic C2C12 cells and single human MSC with
      vector DNA encoding a green fluorescent-erk1 fusion protein (EGFP-ERK1 (MAPK3)).
      Finally, we performed electroporation in combination with live imaging of protein
      expression and dynamics in response to extracellular stimuli, by fibroblast
      growth factor (FGF-2). We observed nuclear translocation of EGFP-ERK1 in both
      cell types within 15 min after FGF-2 stimulation. Due to the successful and
      promising results, we predict that microfluidic devices can be used for highly
      efficient small-scale 'genetic modification' of cells, and biological
      experimentation, offering possibilities to study cellular processes at the single
      cell level. Future applications might be small-scale production of cells for
      therapeutic application under controlled conditions.

PMID- 18094763
TI  - A microfluidic processor for gene expression profiling of single human embryonic
      stem cells.
AB  - The gene expression of human embryonic stem cells (hESC) is a critical aspect for
      understanding the normal and pathological development of human cells and tissues.
      Current bulk gene expression assays rely on RNA extracted from cell and tissue
      samples with various degree of cellular heterogeneity. These 'cell population
      averaging' data are difficult to interpret, especially for the purpose of
      understanding the regulatory relationship of genes in the earliest phases of
      development and differentiation of individual cells. Here, we report a
      microfluidic approach that can extract total mRNA from individual single-cells
      and synthesize cDNA on the same device with high mRNA-to-cDNA efficiency. This
      feature makes large-scale single-cell gene expression profiling possible. Using
      this microfluidic device, we measured the absolute numbers of mRNA molecules of
      three genes (B2M, Nodal and Fzd4) in a single hESC. Our results indicate that
      gene expression data measured from cDNA of a cell population is not a good
      representation of the expression levels in individual single cells. Within the
      G0/G1 phase pluripotent hESC population, some individual cells did not express
      all of the 3 interrogated genes in detectable levels. Consequently, the relative
      expression levels, which are broadly used in gene expression studies, are very
      different between measurements from population cDNA and single-cell cDNA. The
      results underscore the importance of discrete single-cell analysis, and the
      advantages of a microfluidic approach in stem cell gene expression studies.

PMID- 18094764
TI  - A microfluidic bioreactor for increased active retrovirus output.
AB  - Retroviruses are one of the most commonly used vectors in ongoing gene therapy
      clinical trials. To evaluate and advance virus production on the microscale
      platform, we have created a novel microfluidic bioreactor for continuous
      retrovirus production. We investigated the growth kinetics of a retroviral
      packaging cell line in microfluidic bioreactors for several compartment sizes,
      and packaging cells perfused in the microdevices showed similar growth kinetics
      to those cultured in conventional static conditions. To evaluate the efficiency
      of retrovirus production, virus titers from the microdevices were compared to
      those obtained from static tissue culture. When retrovirus production and
      collection were maintained at 37 degrees C, virus production levels were
      comparable for the microdevices and static tissue culture conditions. However,
      immediate cold storage downstream of the packaging cells in the microdevices
      resulted in 1.4- to 3.7-fold greater active virus production levels with the
      microdevices compared to the conventional static conditions over a 5 day period.
      Lastly, the use of microfluidics for virus production provides a continuous
      supply of virus supernatant for immediate infection of target cells or for
      preservation and storage. Such devices will be valuable for the optimization of
      production and evaluation of retroviruses and other viral vectors for gene
      therapy applications.

PMID- 18094765
TI  - Integrated circuit/microfluidic chip to programmably trap and move cells and
      droplets with dielectrophoresis.
AB  - We present an integrated circuit/microfluidic chip that traps and moves
      individual living biological cells and chemical droplets along programmable paths
      using dielectrophoresis (DEP). Our chip combines the biocompatibility of
      microfluidics with the programmability and complexity of integrated circuits
      (ICs). The chip is capable of simultaneously and independently controlling the
      location of thousands of dielectric objects, such as cells and chemical droplets.
      The chip consists of an array of 128 x 256 pixels, 11 x 11 microm(2) in size,
      controlled by built-in SRAM memory; each pixel can be energized by a radio
      frequency (RF) voltage of up to 5 V(pp). The IC was built in a commercial foundry
      and the microfluidic chamber was fabricated on its top surface at Harvard. Using
      this hybrid chip, we have moved yeast and mammalian cells through a microfluidic
      chamber at speeds up to 30 microm sec(-1). Thousands of cells can be individually
      trapped and simultaneously positioned in controlled patterns. The chip can trap
      and move pL droplets of water in oil, split one droplet into two, and mix two
      droplets into one. Our IC/microfluidic chip provides a versatile platform to trap
      and move large numbers of cells and fluid droplets individually for lab-on-a-chip
      applications.

PMID- 18094766
TI  - Microfabricated valveless devices for thermal bioreactions based on diffusion
      limited evaporation.
AB  - Microfluidic devices that reduce evaporative loss during thermal bioreactions
      such as PCR without microvalves have been developed by relying on the principle
      of diffusion-limited evaporation. Both theoretical and experimental results
      demonstrate that the sample evaporative loss can be reduced by more than 20 times
      using long narrow diffusion channels on both sides of the reaction region. In
      order to further suppress the evaporation, the driving force for liquid
      evaporation is reduced by two additional techniques: decreasing the interfacial
      temperature using thermal isolation and reducing the vapor concentration gradient
      by replenishing water vapor in the diffusion channels. Both thermal isolation and
      vapor replenishment techniques can limit the sample evaporative loss to
      approximately 1% of the reaction content.

PMID- 18094767
TI  - Ultra wide-field lens-free monitoring of cells on-chip.
AB  - We experimentally and theoretically demonstrate the proof-of-principle of a new
      lens-free cell monitoring platform that involves using an opto-electronic sensor
      array to record the shadow image of cells onto the sensor plane. This technology
      can monitor/count cells over a field-of-view that is more than two orders of
      magnitude larger than that of a conventional light microscope. Furthermore, it
      does not require any mechanical scanning or optical elements, such as microscope
      objectives or lenses. We also show that this optical approach can conveniently be
      combined with microfluidic channels, enabling parallel on-chip monitoring of
      various different cell types, e.g., blood cells, NIH-3T3 fibroblasts, murine
      embryonic stem cells, AML-12 hepatocytes. An important application of this
      approach could be a miniaturized point-of-care technology to obtain CD4 T
      lymphocyte counts of HIV infected patients in resource limited settings.

PMID- 18094768
TI  - Microfluidic flow-encoded switching for parallel control of dynamic cellular
      microenvironments.
AB  - The temporal pattern of a biological stimulus is an important determinant of the
      resulting cellular response. We present a microfluidic parallel perfusion culture
      system for controlling the dynamics of soluble cell microenvironments while
      simultaneously performing live-cell imaging of cellular responses. A "Flow
      encoded Switching" (FES) design strategy is developed to simultaneously deliver
      many different temporal profiles of stimuli, including pulse train widths,
      lengths, and frequencies, to downstream adherent cells using a single input
      control. The design strategy uses principles of laminar flow and diffusion
      limited mixing to encode the state of the network (the instantaneous stimulus
      concentrations in each channel) into the ratio of two flow rates, which is
      controlled by a single differential pressure. To demonstrate the utility of this
      experimental system, we investigated the effect of dynamic stimuli on NFkappaB
      transcriptional activation and cell fate determination. Our results illustrate
      that transcriptional responses and cell fate decisions depend both quantitatively
      and qualitatively on the timing of the stimulus. In summary, by encoding dynamic
      stimuli in a single input pressure, microfluidic flow-encoded switching offers a
      scalable experimental method for systematically probing the functional
      significance of temporally patterned cellular environments.

PMID- 18094769
TI  - Remotely powered distributed microfluidic pumps and mixers based on miniature
      diodes.
AB  - We demonstrate new principles of microfluidic pumping and mixing by electronic
      components integrated into a microfluidic chip. The miniature diodes embedded
      into the microchannel walls rectify the voltage induced between their electrodes
      from an external alternating electric field. The resulting electroosmotic flows,
      developed in the vicinity of the diode surfaces, were utilized for pumping or
      mixing of the fluid in the microfluidic channel. The flow velocity of liquid
      pumped by the diodes facing in the same direction linearly increased with the
      magnitude of the applied voltage and the pumping direction could be controlled by
      the pH of the solutions. The transverse flow driven by the localized
      electroosmotic flux between diodes oriented oppositely on the microchannel was
      used in microfluidic mixers. The experimental results were interpreted by
      numerical simulations of the electrohydrodynamic flows. The techniques may be
      used in novel actively controlled microfluidic-electronic chips.

PMID- 18094770
TI  - Optical sectioning for microfluidics: secondary flow and mixing in a meandering
      microchannel.
AB  - Secondary flow plays a critical function in a microchannel, such as a micromixer,
      because it can enhance heat and mass transfer. However, there is no experimental
      method to visualize the secondary flow and the associated mixing pattern in a
      microchannel because of difficulties in high-resolution, non-invasive, cross
      sectional imaging. Here, we simultaneously imaged and quantified the secondary
      flow and pattern of two-liquid mixing inside a meandering square microchannel
      with spectral-domain Doppler optical coherence tomography. We observed an
      increase in the efficiency of two-liquid mixing when air was injected to produce
      a bubble-train flow and identified the three-dimensional enhancement mechanism
      behind the complex mixing phenomena. An alternating pair of counter-rotating and
      toroidal vortices cooperated to enhance two-liquid mixing.

PMID- 18094771
TI  - Cell culture arrays using magnetic force-based cell patterning for dynamic single
      cell analysis.
AB  - In order to understand the behavior of individual cells, single cell analyses
      have attracted attention since most cell-based assays provide data with values
      averaged across a large number of cells. Techniques for the manipulation and
      analysis of single cells are crucial for understanding the behavior of individual
      cells. In the present study, we have developed single cell culture arrays using
      magnetic force and a pin holder, which enables the allocation of the magnetically
      labeled cells on arrays, and have analyzed their dynamics. The pin holder was
      made from magnetic soft iron and contained more than 6000 pillars on its surface.
      The pin holder was placed on a magnet to concentrate the magnetic flux density
      above the pillars. NIH/3T3 fibroblasts that were labeled with magnetite cationic
      liposomes (MCLs) were seeded into a culture dish, and the dish was placed over
      the pin holder with the magnet. The magnetically labeled cells were guided on the
      surface where the pillars were positioned and allocated on the arrays with a high
      resolution. Single-cell patterning was achieved by adjusting the number of cells
      seeded, and the target cell was collected by a micromanipulator after removing
      the pin holder with the magnet. Furthermore, change in the morphology of
      magnetically patterned cells was analyzed by microscopic observation, and cell
      spreading on the array was observed with time duration. Magnetic force-based cell
      patterning on cell culture arrays would be a suitable technique for the analysis
      of cell behavior in studies of cell-cell variation and cell-cell interactions.

PMID- 18094772
TI  - Integrated wavelength-selective optical waveguides for microfluidic-based laser
      induced fluorescence detection.
AB  - We demonstrate the fabrication and characterization of a novel, inexpensive
      microchip capable of laser induced fluorescence (LIF) detection using integrated
      waveguides with built-in optical filters. Integrated wavelength-selective optical
      waveguides are fabricated by doping poly(dimethysiloxane) (PDMS) with dye
      molecules. Liquid-core waveguides are created within dye-doped PDMS microfluidic
      chips by filling channels with high refractive index liquids. Dye molecules are
      allowed to diffuse into the liquid core from the surrounding dye-doped PDMS. The
      amount of diffusion is controlled by choosing either polar (low diffusion) or
      apolar (high diffusion) liquid waveguide cores. The doping dye is chosen to
      absorb excitation light and to transmit fluorescence emitted by the sample under
      test. After 24 h, apolar waveguides demonstrate propagation losses of 120 dB cm(
      1) (532 nm) and 4.4 dB cm(-1) (633 nm) while polar waveguides experience losses
      of 8.2 dB cm(-1) (532 nm) and 1.1 dB cm(-1) (633 nm) where 532 and 633 nm light
      represent the excitation and fluorescence wavelengths, respectively. We
      demonstrate the separation and detection of end-labelled DNA fragments using
      polar waveguides for excitation light delivery and apolar waveguides for
      fluorescence collection. We demonstrate that the dye-doped waveguides can provide
      performance comparable to a commercial dielectric filter; however, for the
      present choice of dye, their ultimate performance is limited by autofluorescence
      from the dye. Through the detection of a BK virus polymerase chain reaction (PCR)
      product, we demonstrate that the dye-doped PDMS system is an order of magnitude
      more sensitive than a similar undoped system (SNR: 138 vs. 9) without the use of
      any external optical filters at the detector.

PMID- 18094773
TI  - Pressure-driven fluidic delivery through carbon tube bundles.
AB  - The aim of this work is to demonstrate controlled flow through macroscopically
      long (approximately 1 cm) carbon tubes (0.5-1.8 microm in radius). A model, high
      throughput, pressure-driven fluidic setup, which features a large number of
      parallel carbon tubes forming a bundle, is fabricated and tested. The carbon
      tubes are synthesized and self-assembled via co-electrospinning and subsequent
      carbonization. The setup accommodates pressure-driven flows with flow discharge
      rates of the order of 1 nL s(-1) (73 x 10(-11) kg s(-1)) for low-viscosity
      liquids and 30 nL s(-1) (36.3 x 10(-12) kg s(-1)) for gases into a water pool
      under imposed pressure drops below 4 bar. The measurements demonstrate the
      ability to sustain well-controlled laminar flows through these long carbon tube
      bundles and elucidate the main transport features. A novel procedure is also
      formulated to recover the flow-carrying tube inner-diameter distribution from the
      measured dependence of the fluid volumetric or mass flow rate on the imposed
      pressure drop.

PMID- 18094774
TI  - Controlled on-chip stimulation of quantal catecholamine release from chromaffin
      cells using photolysis of caged Ca2+ on transparent indium-tin-oxide microchip
      electrodes.
AB  - Photorelease of caged Ca(2+) is a uniquely powerful tool to study the dynamics of
      Ca(2+)-triggered exocytosis from individual cells. Using photolithography and
      other microfabrication techniques, we have developed transparent microchip
      devices to enable photorelease of caged Ca(2+), together with electrochemical
      detection of quantal catecholamine secretion from individual cells or cell arrays
      as a step towards developing high-throughput experimental devices. A 100 nm thick
      transparent indium-tin-oxide (ITO) film was sputter-deposited onto glass
      coverslips, which were then patterned into 24 cell-sized working electrodes
      (approximately 20 microm by 20 microm). We loaded bovine chromaffin cells with
      acetoxymethyl (AM) ester derivatives of the Ca(2+) cage NP-EGTA and Ca(2+)
      indicator dye fura-4F, then transferred these cells onto the working ITO
      electrodes for amperometric recordings. Upon flash photorelease of caged Ca(2+),
      a uniform rise of [Ca(2+)](i) within the target cell leads to quantal release of
      oxidizable catecholamines measured amperometrically by the underlying ITO
      electrode. We observed a burst of amperometric spikes upon rapid elevation of
      [Ca(2+)](i) and a "priming" effect of sub-stimulatory [Ca(2+)](i) on the response
      of cells to subsequent [Ca(2+)](i) elevation, similar to previous reports using
      different techniques. We conclude that UV photolysis of caged Ca(2+) is a
      suitable stimulation technique for higher-throughput studies of Ca(2+)-dependent
      exocytosis on transparent electrochemical microelectrode arrays.

PMID- 18094775
TI  - Shrinky-Dink microfluidics: rapid generation of deep and rounded patterns.
AB  - We present a rapid and non-photolithographic approach to microfluidic pattern
      generation by leveraging the inherent shrinkage properties of biaxially oriented
      polystyrene thermoplastic sheets. This novel approach yields channels deep enough
      for mammalian cell assays, with demonstrated heights up to 80 microm. Moreover,
      we can consistently and easily achieve rounded channels, multi-height channels,
      and channels as thin as 65 microm in width. Finally, we demonstrate the utility
      of this simple microfabrication approach by fabricating a functional gradient
      generator. The whole process--from device design conception to working device-
      can be completed within minutes.

PMID- 18094776
TI  - Nanochannels in SU-8 with floor and ceiling metal electrodes and integrated
      microchannels.
AB  - Sacrificially etched 2-D nanofluidic channels and nanospaces with integrated
      floor and ceiling electrodes and arbitrary channel geometries have been
      demonstrated with channel heights from 20 nm to 400 nm, widths from 800 nm to 40
      microm, and lengths up to 3 mm, using SU-8 as the channel structural material.

PMID- 18094777
TI  - Analysis of pressure-driven air bubble elimination in a microfluidic device.
AB  - We report an analysis of pressure-driven bubble elimination for a gas-permeable
      microfluidic device. In this study, we described bubble elimination in a
      microfluidic device employing a gas permeation model and calculated the removal
      efficiency of bubbles. The correction factor for the simplified model was
      estimated with respect to the applied pressure. Based on the established model,
      the required time to remove a trapped bubble with a certain area was shown to be
      within an error of 11.58% by comparison with experimental results. Exploiting the
      model equation, we were able to completely remove the air bubbles appearing
      during the process of filling a microfluidic device with an aqueous solution.

PMID- 18094778
TI  - [Living with AIDS].

PMID- 18094779
TI  - [Foreword. Sexually transmitted diseases and AIDS research].

PMID- 18094780
TI  - [Introduction. AIDS epidemic in Brazil].

PMID- 18094781
TI  - [Invisibility of drug use and support for professionals of the AIDS services].
AB  - OBJECTIVE: To describe the influence of conceptions of health professionals on
      the care given to HIV/AIDS patients using drugs. METHODS: Qualitative study based
      on semi-structured interviews with 22 professionals of different levels from two
      specialized STD/AIDS public services of the city of Sao Paulo was conducted in
      2002. The interviews were recorded and submitted to a thematic analysis. RESULTS:
      Professionals reported difficulties in identifying drug users among their
      patients, indicating the invisibility of the issue. They find drug users more
      difficult to treat, because they disturb the service and do not comply with
      treatment. Although they acknowledge the special needs of users, and that it is
      important to deal with drug use, health professionals believe that these issues
      are not their responsibility. Professionals showed personal and technical limits
      in handling these cases, showing the importance of their lack of specific
      capacity building. Thus, they recommend the creation of specialized services for
      this care, recognizing their own services as inappropriate. Although they were
      aware of the harm reduction project, there was a little participation in it.
      CONCLUSIONS: Technical, ideological and personal elements such as beliefs, values
      and affective/emotional dimensions were relevant to enhance or refuse to develop
      more specific bonds with drug user patients. The conceptions on drug use may
      interfere in the development of a better care and equity in health care.

PMID- 18094782
TI  - [Injecting drug users and antiretroviral therapy: perceptions of pharmacy teams].
AB  - OBJECTIVE: To understand the perceptions of pharmacy teams about their role in
      the healthcare assistance challenges and adherence to antiretroviral therapy by
      injecting drug users living with HIV/AIDS. METHODS: Qualitative study through
      focus groups and thematic discourse analysis of pharmacists, technicians and
      assistants with more than six months of experience with medication supply, in 15
      assisting units for STD/AIDS in the city of Sao Paulo, in 2002. RESULTS: Three
      groups were formed, totaling 29 participants, originating from 12 out of the 15
      existing services, and including 12 university level professionals and 17 high
      school level professionals. The groups concluded that the pharmacy has an
      important role in the antiretroviral drug supply, which is reflected in the
      treatment adherence, because trust-based relationships can be built up through
      their procedures. In spite of this, they pointed out that such building-up does
      not take place through excessively bureaucratic activities. This has negative
      repercussions for all patients, especially for injecting drug users, considered
      "difficult people". Such concept sums up their behavior: they are supposed to be
      confused and incapable to adhere to treatment, and have limited understanding.
      Staff members, however, affirm they treat these patients equally. They do not
      realize that, by this acting, the specific needs of injecting drug users may
      become invisible in the service. There is also the possibility that stigmatizing
      stereotypes may be created, resulting in yet another barrier to the work on
      adherence. CONCLUSIONS: Although the pharmacy is recommended as a potentially
      favorable place to listen to and form bonds with users, the results show
      objective and subjective obstacles to render it suitable for the work on
      adherence.

PMID- 18094783
TI  - [Vulnerability to HIV among female injecting drug users].
AB  - OBJECTIVE: To assess some aspects of vulnerability to HIV infection in women
      users of injecting drugs. METHODS: Thirteen semi-structured interviews were
      performed with female drug users (or former users) of injecting drugs, leaving in
      the East side of Sao Paulo, in 2002. The script of interviews approached four
      focal point issues: socioeconomic context and affective relationships, drug use,
      prevention against HIV and health care. Interviews were assessed through content
      analysis. RESULTS: Poverty, absence of strong and continuous affective ties,
      being expelled from the family and school, exposure to violence,
      institutionalization, drug use, criminality, and discrimination were constant in
      interviewees' reports. These aspects made it difficult to adopt practices for HIV
      prevention such as the use of condoms, disposable syringes and needles, and
      looking for health care services. CONCLUSIONS: Vulnerability to HIV infection
      makes it clear the fragility use have effective access to social, economic and
      cultural rights, requiring welfare policies of specific population segments such
      as women (children and adolescents), low income citizens, people living in the
      outskirts, with poor access to educational, cultural and health resources. This
      access is complicated especially for those that are discriminated by behaviors
      such as drug use.

PMID- 18094784
TI  - [Women living with HIV/AIDS who are sexual partners of injecting drug users].
AB  - OBJECTIVE: To analyze perceptions of risk, prevention strategies, their own
      relationship with drug use and that of their partner's, and future expectations
      among women living with HIV/AIDS whose partners are drug users. METHODS: This is
      a qualitative study of women living with HIV/AIDS who receive specialist
      treatment in Sao Paulo Municipality. Semi-structured interviews were carried out
      with 15 women, whose self-reported means of infection were heterosexual relations
      with a partner who is an injecting drug user. The script for the interviews
      covered the following areas: childhood, history of sexual relations, use of
      drugs, impact of seropositivity on daily life, understanding of the prevention of
      sexually transmitted infections, and perspectives of the future. The material
      from the interviews was analyzed using content analysis. RESULTS: The study
      pointed to a difference in the ways that the women live with their own drug use
      and with that of their partners. Their partners' use of injecting drugs was not
      primarily associated with a risk of HIV infection, due to attempts to conceal the
      fact or because they believed that the monogamy-fidelity-confidence trinity would
      take precedence as a form of protection. CONCLUSIONS: The women's different
      experiences of drug use should be taken into account and opportunities to discuss
      with them about the issue are important to ensure that more effective strategies
      for prevention and care are adopted.

PMID- 18094785
TI  - [Black and non-Black women and vulnerability to HIV/AIDS in Sao Paulo, Brazil].
AB  - OBJECTIVE: To analyze the characteristics related to individual vulnerability
      among HIV seropositive women, according to skin color. METHODS: A multicenter
      study carried out between 1999 and 2000 in health services specialized in
      STI/Aids in the state of Sao Paulo, involving 1,068 women living with HIV who are
      aged 18 or above. Sociodemographic data and characteristics relating to infection
      and healthcare were obtained by means of individual interviews based on
      standardized questionnaire. The variable race/color was self-reported and women
      who referred to themselves as black or mixed-race were grouped together as black.
      The definition of variables by race/color was done using central tendency and
      proportions, and an association analysis using the chi2 Pearson test. RESULTS:
      The differences between black and non-black women were statistically significant
      with regards to: schooling; monthly, individual and family income per capita;
      number of direct dependents; opportunities to see a nutritionist, gynecologist or
      other medical professional; understanding what the infectologist said; speaking
      with the infectologist or gynecologist about her sex life; having correct
      knowledge about CD4 exams and viral load; the sexual means of exposure.
      CONCLUSIONS: The use of race/color as an analytical category provides
      opportunities to understand better how social interactions, in the context of
      gender and socioeconomic conditions, create and recreate disadvantages for black
      women and their exposure to health risks, and also impose limits on the way they
      use of resources for their healthcare.

PMID- 18094786
TI  - [HIV infection, hepatitis B and C and syphilis in homeless people, in the city of
      Sao Paulo, Brazil].
AB  - OBJECTIVE: To estimate the prevalence of HIV infections, as well as hepatitis B
      and C and syphilis viruses in homeless people. METHODS: Cross-sectional study
      with educational intervention, conducted in the city of Sao Paulo, between 2002
      and 2003. A convenience sample of homeless people who used night shelters was
      selected, according to the following criteria: aged 18 or older and not showing
      psychiatric disturbances. During interviews, sociodemographic and behavioral data
      were gathered and HIV, hepatitis B and C and syphilis laboratorial tests and post
      test counseling were carried out. RESULTS: A total of 330 shelter users
      participated, with an average age of 40.2 years, 80.9% of them male, having lived
      on the streets for one year in average. Prevalences of 1.8% for HIV, 8.5% for
      hepatitis C virus, 30.6% for previous hepatitis B infection, 3.3% for chronic or
      acute infection by hepatitis B virus, and 5.7% for syphilis. The consistent use
      of condoms was referred to by 21.3% of interviewees and the use of injecting
      drugs by 3% of them. Positivity was 10% for HIV and 50% for hepatitis C virus
      among injectable drug users, versus 1.5% for HIV and 7.3% for hepatitis C among
      the others, showing an association between the virus and the use of injecting
      drugs. Previous imprisonment was referred to by 7.9% of women and 26.6% of men,
      with a prevalence of 2.6% for HIV and 17.1% for hepatitis C virus. CONCLUSIONS:
      The high prevalences of HIV and hepatitis B and C viruses require prevention
      programs based on vaccination against hepatitis B, early diagnosis of these
      infections and placement of homeless people into health services.

PMID- 18094787
TI  - [Hepatitis B and C among injecting drug users living with HIV in Sao Paulo,
      Brazil].
AB  - OBJECTIVE: To describe the profile of injecting drug users living with HIV/AIDS
      and estimate hepatitis B and hepatitis C prevalence rates within this group.
      METHODS: Cross-sectional study conducted with 205 injecting drug users living
      with HIV/AIDS receiving attention in three public health clinics in the city of
      Sao Paulo, in 2003. A non-probabilistic sample of volunteers was selected
      consecutively on the days respondents appeared for their appointments at the
      clinics. Personal data and information on sexual behavior, drug use and knowledge
      of hepatitis was collected through interviews. Tests were conducted to detect
      infections of the hepatitis B and C viruses. RESULTS: Out of the interviewees,
      81% were men and 19% women, with an average age of 39 (SD=6.1) and six years of
      formal education (SD=2.0). There was no difference in marital status between the
      sexes, of which 48% were single, 42% were married, and 8% were divorced. The
      average ages for first use of tobacco, alcohol and illegal drugs were 13, 15 and
      18, respectively. Hepatitis B and C prevalence were 55% (95% CI: 49;63) and
      83%(95% CI: 78;88), respectively. Eighty percent of respondents had not heard of
      Hepatitis B and C prior to the first time they used injecting drugs. CONCLUSIONS:
      The high prevalence rates of Hepatitis B and C and low level of knowledge
      regarding the diseases justify the inclusion of information about hepatitis
      infections and the hepatitis B vaccines in HIV harm reduction strategies.

PMID- 18094788
TI  - [Quality of life of people living with HIV/AIDS in Sao Paulo, Brazil].
AB  - OBJECTIVE: To assess quality of life of people living with HIV/AIDS. METHODS:
      Cross-sectional study conducted in an AIDS outpatient service based on
      consecutive sampling during the second half of the year 2002. There were selected
      365 men and women aged 18 years or older who were attended by the infectious
      disease physician. Sociodemographic and recent drug use variables and data on
      clinical conditions were obtained using a questionnaire and quality of life was
      analyzed using WHOQOL-bref. RESULTS: Scores of the four domains (physical,
      psychological, social relationships and environment) were very similar. There
      were statistically significant differences in mean scores for the environment
      domain according to skin color, with blacks and pardos having lower scores. Women
      also had the lowest scores for the psychological and environmental domains.
      Higher income was significantly associated to higher scores in all domains of
      quality of life, except for the social relationships domain. Subjects with CD4+
      cell counts below 200 cells/mm(3) had lower scores for the physical domain. In
      all domains significantly lower scores were seen for those receiving psychiatric
      treatment or with an indication for such treatment. CONCLUSIONS: Despite
      differences in sex, skin color, income, and mental and immunological status,
      people living with HIV/AIDS have better (physical and psychological) quality of
      life than other patients but lower quality in social relationships domain. The
      latter domain could reflect stigmatization and discrimination associated to the
      difficulties of disclosing their HIV status in social settings and for a safe sex
      life.

PMID- 18094789
TI  - [AIDS, stigma and unemployment: implications for health services].
AB  - OBJECTIVE: To analyze the effect of the stigmatization and discrimination process
      in the work environment on the routine healthcare and well-being of men living
      with HIV/AIDS. METHODS: Qualitative study with 17 men living with HIV, conducted
      in 2002. Testimonies given in a group to discuss the difficulties concerning
      discrimination in the work environment were studied, by means of discursive
      practice analysis. The group, originating from a specialized center for HIV/AIDS
      treatment in the city of Sao Paulo, represented a segment of previous research.
      RESULTS: The discussion among participants pointed out the fact that
      antiretroviral treatment requires frequent visits to medical assistance services,
      resulting in absences and delays at work. To show medical certificates to justify
      absences at work, even without indicating AIDS, can lead to dismissal.
      Unemployed, many are barred during medical examinations and have their right to
      confidentiality violated. As a last resource, the request for retirement results
      in a humiliating or discriminatory scene during the medical inspection.
      CONCLUSIONS: Assistance planned with the patients' participation enables the
      broadening of psychosocial attention and the consideration of the needs of both
      employed and unemployed patients, acknowledging that the stigma limits care,
      affecting mental health and the evolution of infection. To reduce the effect of
      stigma and discrimination is something that requires intersectoral political
      articulation and will contribute to reach goals that are globally recognized as
      fundamental to control the epidemic.

PMID- 18094790
TI  - [Vulnerability to HIV: tourism and the use of alcohol and other drugs].
AB  - OBJECTIVE: To describe situations of alcohol and other drug use involving
      tourists, and their implications regarding vulnerability to HIV. METHODS: This
      was an exploratory qualitative study conducted in communities that host tourism
      in the Vale do Ribeira, State of Sao Paulo, from October 2002 to February 2003.
      In the first stage of the study, 29 monitors in four host communities were
      interviewed to gather scenarios of drug use involving tourists. In the second
      stage, two workshops were held, bringing together 77 interviewees and health and
      education professionals from ten communities, in order to dramatize the scenarios
      gathered in the interviews and share repertoires for dealing with these
      situations and finding ways for preventing HIV. RESULTS: The scenarios showed
      that alcohol and other drug use by tourists increases their vulnerability to HIV
      transmission through favoring casual sexual intercourse without condoms and
      sexual harassment and abuse. HIV prevention work in these communities that host
      tourism needs to take into account the consumption of these substances which use
      creates difficulties regarding safe sex practices and, in the case of injecting
      drugs that are shared, constitutes a risk factor for HIV transmission.
      CONCLUSIONS: This study provided data to help in understanding how situations of
      alcohol and other drug use fit within daily life in these host communities,
      thereby extending the vulnerability to HIV. The study produced analysis of the
      social context of HIV transmission that may provide backing for drawing up
      prevention programs that are better adapted to these communities.

PMID- 18094791
TI  - [Challenges of treatment adherence by people living with HIV/AIDS in Brazil].
AB  - OBJECTIVE: To analyze the difficulties related to treatment adherence by patients
      living with HIV/AIDS in highly active antiretroviral therapy. METHODS:
      Qualitative research based on 34 interviews with patients under treatment in
      several outpatient services in the state of Sao Paulo, in 1998-1999. The group
      was comprised of people from different socioeconomic levels, gender, length of
      treatment and varied adherence levels, according to healthcare staff perception.
      The interviews focused on the patient's narrative about his/her disease. The
      content analysis classified the difficulties as follows: related to social
      factors and life styles, including the stigma; related to beliefs about the use
      of medication; and directly related to the use of medication. RESULTS: All the
      interviewees reported having difficulties concerning the stigma of living with
      HIV/AIDS. The difficulties related to the use of medication were the most
      important among patients with the best adherence level. Patients with average
      adherence level presented all three types of difficulties. CONCLUSIONS: Social
      and cultural factors are more difficult to be overcome in order to achieve
      treatment adherence than those related to taking medication, thus making the role
      played by the health sector important, supported by clear public social policies.
      These dimensions must be faced not only in the health sector, but also on social
      and political levels.

PMID- 18094792
TI  - [Perceptions of HIV rapid testing among injecting drug users in Brazil].
AB  - OBJECTIVE: To describe perceptions, experiences, knowledge, beliefs and the
      willingness of injecting drug users to be HIV tested by using rapid tests.
      METHODS: A qualitative exploratory study was carried out among injecting drug
      users from December 2003 to February 2004 in five Brazilian cities, located in
      four regions of Brazil. A semi-structured interview guide containing both closed
      and open-ended questions was used to address perceptions about non-conventional
      testing procedures, and non-traditional ways to provide testing access to
      injecting drug users. A total of 106 interviews, about 26 per region, were
      conducted. RESULTS: Characteristics of the population studied, common thoughts
      about HIV rapid testing, preference for using blood or saliva specimens, and
      other testing preferences, were presented together with reported advantages and
      disadvantages of each option. The study findings showed that the use of rapid
      tests among these users is feasible and that they are willing to be tested using
      rapid HIV tests, especially if some issues related to privacy and reliability of
      the test could be addressed. CONCLUSIONS: The study findings showed that rapid
      tests may be well accepted for this population. These tests can be considered a
      valuable tool, allowing a more injecting drug users to learn their HIV status and
      possibly be referred to treatment and should support more effective testing
      strategies for them.

PMID- 18094793
TI  - [HIV infection among pregnant women attended in testing and counseling centers
      for AIDS].
AB  - OBJECTIVE: To estimate HIV prevalence and identify high-risk sexual behavior for
      infection in pregnant women who were given prenatal assistance. METHODS: Cross
      sectional study based on attendance records of 8,002 pregnant women (25% of all
      municipalities) who lived in 27 municipalities in Southern Brazil in 2003 and had
      anti-HIV tests done in a testing and counseling center that performed prenatal
      assistance. Sociodemographic and behavioral data were gathered, as well as
      syphilis and HIV test results, during the individual counseling sessions
      registered in the data bank of the Sistema de Informacoes dos Centros de Testagem
      e Aconselhamento (Information System on Testing and Counseling Centers). Women
      who sought the centers for confirmation of previous serology or were referred to
      this service due to the presence of AIDS symptoms were excluded from the data
      base. RESULTS: A total of 0.5% of all the pregnant women analyzed (CI
      95%=0.3;0.6) were HIV positive. The only variable associated with HIV
      seropositivity was schooling. The majority of them were basically exposed through
      unprotected sexual intercourse with the only partner they had a steady
      relationship with. Younger pregnant women who were single, unemployed and had
      lower level of education constituted the group with highest exposure.
      CONCLUSIONS: The Sistema de Informacoes dos Centros de Testagem e Aconselhamento
      turned out to be useful for the epidemiological surveillance of HIV infection and
      high-risk behavior among pregnant women and could also be useful as regards other
      populations.

PMID- 18094794
TI  - [Differences in HIV-risk behavior of bisexual men in their relationships with men
      and women].
AB  - OBJECTIVE: To describe bisexual men's behavior in terms of sexual identity,
      condom use, frequency of sexual intercourse and types of partners and to
      determine rates of inconsistent condom according to partner's gender. METHODS:
      Cross-sectional study nested in a cohort of HIV-negative homosexual and bisexual
      men in the city of Belo Horizonte, Southeastern Brazil, followed up since 1994
      (Horizonte Project). Of 1,025 subjects enrolled between 1994 and 2005, 195
      volunteers who reported at admission having sexual relations with men and women
      during the previous six months were selected. A behavioral risk index, called
      Horizonte Risk Index, was estimated. It incorporates a constant assigned to each
      type of unprotected sexual act, adjusted for the number of sexual encounters.
      RESULTS: Sexual activity with men predominated; most considered themselves as
      bisexual (55%) and homosexual (26%). During the six months prior to the study,
      median number of casual male partners (4) was higher than both casual female
      partners (2) and steady male or female partners (1). During vaginal sex with a
      steady partner, the rate of inconsistent condom use was 55%, compared to 35% and
      55% in anal insertive and anal receptive sex, respectively, with steady male
      partners. The index was higher for those having sex with men and women compared
      to those having sex either exclusively with women or men (p=0.004). CONCLUSIONS:
      HIV risk behavior was more frequent among men who reported sexual activity both
      with men and women. Bisexual men display different sexual and protective behavior
      according to gender and steadiness of relationships, and female steady partners
      had more unprotected encounters.

PMID- 18094795
TI  - [Community-based intervention to control STD/AIDS in the Amazon region, Brazil].
AB  - OBJECTIVE: To describe a case study of community-based intervention, developed in
      a constructionist-emancipatory framework to control STD/AIDS. METHODS:
      Descriptive study developed in the town of Manacapuru, in the state of Amazonas,
      from 1997 to 2004, focusing on procedures designed in collaboration with
      government agents, health professionals and the community. Data on the dynamics
      of prostitution and condom sales in this town, preventive practices and STD/AIDS
      care and process assessment were collected. Actions targeting STD prevention and
      care in the public healthcare system, a testing center, an epidemiological
      surveillance system and sex workers' qualification were established
      concomitantly. RESULTS: It was observed the strengthening of sex workers as peer
      educators and their legitimization as citizens and health agents in projects
      involving transvestites, homosexuals and students. There was an increase in
      condom sales in town, as well as in condom use among sex workers; reduction in
      bacterial STD; and stabilization of the incidence of HIV/AIDS infections and
      congenital syphilis. The sustainability of the intervention program studied,
      organized within the sphere of action of the Sistema Unico de Saude (National
      Health System), was promoted by a political pact, which guaranteed headquarters
      and municipal law-regulated budget, as well as by the constant debate over the
      process and program results. CONCLUSIONS: The study strengthened the notion that
      effective control of STD/AIDS depends on a synergic approach that combines
      interventions on individual (biological-behavioral), sociocultural and
      programmatic levels.

PMID- 18094796
TI  - [HIV vulnerability in a shantytown: the impact of a territorial intervention, Rio
      de Janeiro, Brazil].
AB  - OBJECTIVE: To analyze the impact of a participatory sexual health promotion
      program implemented in a poor community and describe how the use of public and
      private spaces for sex is a factor that exacerbates vulnerability to HIV/Aids.
      METHODS: This ethnographic study was conducted in a Rio de Janeiro shantytown in
      2002. Six thousand people live in precarious living conditions in which the lack
      of public policies, health posts, recreational activities, employment
      opportunities, and security consolidates power in criminal groups. Issues related
      to sexual health were addressed in addition to a participatory sexual health
      program implemented by a Community HIV Prevention Center established by a non
      governmental organization. After two months of participatory observation, 35 semi
      structured in-depth interviews were conducted with community members between the
      ages of 17 and 65. Eleven life histories of community leaders and HIV prevention
      promoters and seven focus groups formed from pre-existent community groups were
      analyzed. The material was categorized and analyzed qualitatively. RESULTS: The
      precarious nature of living conditions contributes to increased exposure to
      sexual practices while also enhancing the stigma experienced by the community for
      living in a shantytown. Through the implementation of the program by the
      Community HIV Prevention Center, children, teenagers and adults have become
      familiar with and knowledgeable of HIV/AIDS prevention; and teenagers and adults
      gained access to condoms. CONCLUSIONS: Although vulnerability to HIV was not
      affected, research results reveal that HIV prevention can become part of the
      local culture. HIV/AIDS prevention can be fomented by a local approach based on
      community participation and strengthening collective organizing.

PMID- 18094797
TI  - Sinusitis orbitary complications classification: simple and practical answers.

PMID- 18094798
TI  - A comparative study of the breathing pattern and amount of nasopharynx
      obstruction by the pharyngeal tonsil in HIV infected and non infected children.
AB  - AIM: the goal of the present investigation was to study the association between
      breathing pattern and pharyngeal tonsil size in 122 children (60 HIV infected and
      62 without such infection). MATERIAL AND METHODS: The children were analyzed as
      to their breathing pattern, nasal flow and pharyngeal tonsil obstruction seen in
      side cephalometric x-rays, by means of a computerized analysis. RESULTS: The
      pattern that most occurred in both groups was the mixed type. Most of the
      children presented oral or mixed type breathing and there was no association
      between the type of breathing and HIV presence (p=0.091). Nasal flow was mainly
      medium in both groups. Children without prior history of HIV infection had medium
      to large nasal flow and most of the HIV-infected children had medium nasal
      airflow. There was a positive association between nasal flow and HIV infection
      (p<0.0001). The average percentage of nasopharynx obstruction by the pharyngeal
      tonsil was high in both groups, and there was no statistically significance
      difference between them. Children from both groups had a moderate or large size
      of pharyngeal tonsil, and there was no association between tonsil size and HIV
      (p=0.21).

PMID- 18094799
TI  - The efficiency of otoacoustic emissions and pure-tone audiometry in the detection
      of temporary auditory changes after exposure to high sound pressure levels.
AB  - Exposure to noise has a harmful effect on the auditory health of workers. AIM:
      The main goal of this paper was to establish the role of pure-tone audiometry and
      evoked transient otoacoustic emissions in the detection of small temporary
      auditory changes after exposure to high sound pressure levels. STUDY DESIGN: A
      cross-sectional cohort study. MATERIAL AND METHODS: 30 otologically normal
      subjects aged between 20 and 35 years were submitted to pure-tone audiometry and
      evoked transiente otoacoustic emissions before and after 5 hours of exposure to
      high sound pressure levels (between 80 and 90 dB). RESULTS: For pure-tone
      audiometry the largest changes occurred at high frequencies--from 3 KHz to 8 KHz
      after exposure. The evoked transient otoacoustic emissions showed reduced
      reproductibility from 1 KHz to 4 KHz after exposure to noise. CONCLUSION: We
      noted that both pure-tone audiometry and evoked transient otoacoustic emissions
      had a role in detecting statistically significant changes in the auditory
      threshold and in reproductibility, after exposure to high sound pressure levels.

PMID- 18094800
TI  - Impact of acupuncture on otoacoustic emissions in patients with tinnitus.
AB  - The treatment of tinnitus is still a challenge. Acupuncture is recommended for
      the relief of tinnitus in traditional Chinese Medicine, although scientific
      evidence is lacking. AIM: The aim of this study was to assess the effect of
      acupuncture on the cochlear function in patients with tinnitus by analyzing
      otoacoustic emissions. METHODS: Thirty eight patients with tinnitus were included
      in the prospective clinical study. Measures of transitory otoacoustic emissions
      and suppression of otoacoustic emissions were obtained from all subjects before
      and after acupuncture. Patients were assigned to one of two groups: intervention
      group 1 (n=19), in which needle acupuncture was applied at the temporoparietal
      point corresponding to the vestibulocochlear area, and intervention group 2
      (n=19), in which the needle was applied 3 cm cranially to this area (which is not
      a recognized acupuncture point). RESULTS: There was a significant difference
      between the amplitude of otoacoustic emissions assessed before and after
      acupuncture in intervention group 1. No difference was observed in intervention
      group 2. CONCLUSION: Acupuncture had a significant effect on otoacoustic
      emissions in patients with tinnitus.

PMID- 18094801
TI  - The prevalence of hearing loss in children and adolescents with cancer.
AB  - The treatment of cancer in children has several side effects, including
      ototoxicity. Inner ear structures may be affected and hearing loss may ensue.
      AIM: To estimate the prevalence of hearing loss in patients with cancer using the
      American Speech-Language-Hearing Association (ASHA), the Pediatric Oncology Group
      Toxicity (POGT), and the Bilateral Hearing Loss (PAB) criteria. STUDY DESIGN: a
      prospective study. MATERIAL AND METHODS: 94 patients admitted between 2003 and
      2004 were analyzed. Visual inspection of the external auditory meatus and an
      audiologic evaluation were done. Descriptive statistics was used to characterize
      the sample, and Kappa statistics was used to investigate concordance of hearing
      loss in the three types of classification. RESULTS: The prevalence of hearing
      loss was 42.5% using ASHA, 40.4% using POGT, and 12.8% using PAB. The concordance
      of hearing loss was weak for POGT and PAB (k=0.36) and for PAB and ASHA (k=0.33).
      The concordance between ASHA and POGT was almost perfect (k=0.96). CONCLUSIONS:
      Hearing loss is an important side effect of the treatment of cancer in children.
      Periodic audiology monitoring is recommended to detect early hearing loss and to
      revise the treatment if necessary. Adoption of a classification system that
      detects mild hearing loss (ASHA) is recommended.

PMID- 18094802
TI  - Evaluation of airway obstruction by nasopharyngoscopy: comparison of the Muller
      maneuver versus induced sleep.
AB  - The use of nasopharyngoscopy during the application of intrathoracic pressure
      (Muller maneuver) is frequently employed to establish the site of upper airway
      obstruction. The Muller maneuver, however, is used when the patient is awake and
      therefore may not correlate with obstruction occurring during sleep. AIM: To
      compare the degree of pharyngeal obstruction in the retropalatal and retroglossal
      regions during the Muller maneuver versus induced sleep using nasopharyngoscopy.
      STUDY DESIGN: A prospective, case series study. MATERIAL AND METHODS: Eight
      patients (three males, five females), with a mean age of 48.6 +/- 9.2 year,
      underwent nasopharyngoscopy to assess airway anatomy and function during the
      Muller maneuver while awake and during sleep induced by drip infusion of
      Midazolam. RESULTS: Retropalatal obstruction was similar during the Muller
      maneuver and sleep (mean + standard deviation = 3.13 +/- 0.99 and 2.75 +/- 0.46,
      p= 0.234). Retroglossal obstruction was significantly lower during Muller
      maneuver compared to sleep (mean + standard deviation 0.63 +/- 1.06 and 2.63 +/-
      1.30, respectively, p= 0.005). CONCLUSIONS: The sleep inducing method was safe
      under the monitored conditions of this study, and detected more retroglossal
      obstruction than the Muller maneuver.

PMID- 18094803
TI  - Comparative study of several sinusitis experimental modelling techniques in
      rabbits.
AB  - Experimental models for clinical studies of rhinosinusitis are needed. AIM: to
      define a reliable, solid and reproducible experimental model for inflammatory
      rhinosinusitis with no innoculation of infectious agents in rabbits. STUDY
      DESIGN: Experimental. MATERIAL AND METHOD: Twenty 20 rabbits were divided into 4
      groups submitted to 4 different interventions: the placement of a unilateral
      nasal fossa sponge, unilateral obliteration of the nasal ostium with
      cyanoacrylate, unilateral placement of antigens in the maxillary cavity and
      unilateral placement of blood in the maxillary cavity. The animals were monitored
      for 15 days and then anesthetized and sacrificed; the maxillary sinuses were
      evaluated histologicaly and results were compared with controls and between the
      intervention groups. CONCLUSION: Sponje and glue as agents of meatal obstruction
      and toxoid applied in the antrum are efficient as methods for rhinosinusitis
      modeling. Blood was not efficient in producing sinusitis.

PMID- 18094804
TI  - Tympanometry in neonates with normal otoacoustic emissions: measurements and
      interpretation.
AB  - Tympanometry is used in evaluating middle ear functional conditions. Before six
      months of age its results may be misleading. High frequency studies aim to
      provide more valid procedures. AIM: To describe and discuss tympanometric
      measurements and the interpretation in normal hearing neonates at 226, 678 and
      1000Hz. METHOD: 110 neonates that were analyzed had normal otoacoustic emissions
      and no risk for hearing impairment. The age range was 6 to 30 days. Curves were
      obtained using the GSI-33-II, at the Divisao de Educacao e Reabilitacao dos
      Disturbios da Comunicacao, Sao Paulo, in 2004. STUDY DESIGN: Clinical
      prospective. RESULTS: There was a balance between single and double peak curves
      at 226Hz. Most of the curves were asymmetric at 678Hz, and single-peaked at
      1000Hz. quantitative measurements showed a significant gender difference in the
      Equivalent Ear Canal Volume at 226Hz and on the Peak Compensated Static Acoustic
      Admittance at 1000Hz. The English protocol showed that almost 100% of ears were
      normal at 678 and 1000Hz. CONCLUSION: 1000Hz yielded superior results for
      characterizing normality. The English protocol was efficient to reduce the
      variability of tympanometric measurements. Data from this study may be used as a
      guide for diagnosis using tympanometry in neonates.

PMID- 18094805
TI  - Radical versus supraomohyoid neck dissection in the treatment of squamous cell
      carcinoma of the inferior level of the mouth.
AB  - The therapeutic paradigm for neck metastasis of squamous cell carcinoma (SCC) in
      the lower level of the mouth has changed due to survival. AIM: A comparative
      study between radical (RND) versus selective neck dissection (SND). MATERIAL AND
      METHOD: An analysis of mouth SCC in the lower level of the mouth in 460 files
      from the Head & Neck and ORL Department of the Heliopolis Hospital, from 1978 to
      2002. In the RND the metastathic rate in levels IV and V was assessed; in the SND
      the presence and site of recurrence was identified. The chi square test with the
      Yates correction was the chosen statistical method. RESULTS: In the RND the
      metastatic rates were 5.8% (level IV) and 4.6% (level V) for cNO cases, and 9.9%
      (level IV) and 5.9% (level V) for cN+ cases; for level I only the rates were
      11.0% for cNO cases and 5.5% for cN+ cases. In the SND the number of recurrences
      was 4 (4.1%) in 97 neck dissections (pNO) and 2 (10%) in 20 neck dissections
      (pN+). There was no advantage in using radiation compared to non-irradiated cases
      (5.6% and 5.7%). CONCLUSION: The SND may be used for SCC of the lower level of
      the mouth.

PMID- 18094806
TI  - Stapes surgery in residency: the UFPR clinical hospital experience.
AB  - Surgery of the stapedius remains the established treatment for otosclerosis.
      Recent publications have showed that success in surgeries done by residents have
      decreased and hearing results are worse than those obtained by experienced
      otologic surgeons. AIM: To evaluate the experience of the otorhinolaryngology
      unit, Parana University, relative to stapes surgery done in the residency
      training program. MATERIAL AND METHOD: A retrospective study of 114 stapes
      surgeries done in the past 9 years in 96 patients. Audiometric results were
      analysed according to the Committee on Hearing and Equilibrium guidelines and the
      Amsterdam Hearing Evaluation Plots. The improvement of the airway postoperative
      gap and thresholds were taken into account. RESULTS: 96 patients were included,
      most of them female adults (67.7%) and white (93.7%). Stapedectomy was done in
      50.9% of cases, mostly under local anesthesia and sedation (96.5%), using mostly
      the Teflon prosthesis (37.7%). The surgical success rate was 50.88%, there was an
      11.4% complication rate. CONCLUSION: Postoperative hearing gains considered as
      surgical success were inferior to published results in the literature, done by
      experienced surgeons.

PMID- 18094807
TI  - The prevalence of hearing loss in an elderly population in Rio de Janeiro: a
      cross-sectional study.
AB  - Hearing loss in the elderly is one of the most frequent chronic diseases. AIM: to
      estimate the prevalence of hearing loss in a representative sample of elderly
      people (aged 65 or over) in the city of Rio de Janeiro. MATERIAL AND METHOD: a
      prospective, cross-sectional population-based study with 238 elderly people aged
      65 years or more (198 women and 40 men). RESULTS: the prevalence of hearing loss
      was 39.4% (better ear) and 61.6% (worse ear) in the female group, 60% (better
      ear) and 77.5% (worse ear) in the male group, and 42.9% and 64.3% in the study
      population. Mild hearing loss was the most prevalent level of hearing loss.
      CONCLUSION: the prevalence of hearing loss in the study population was
      significant and in accordance with others relevant international epidemiological
      studies. Longitudinal studies are needed to better understand age-related hearing
      loss.

PMID- 18094808
TI  - Hearing aid fitting process in users fitted in a federal public institution: part
      II--Self-assessment questionnaire results.
AB  - An efficient rehabilitation must be able to reduce impairment effects over the
      auditory and communication skills of individuals and promote psychosocial well
      being. AIMS: check the feasibility of using self-assessment questionnaires and
      compare the results achieved by hearing aid fitting in users from a federal
      public institution, with and without complaints related to hearing amplification
      characteristics. MATERIALS AND METHODS: 25 individuals, from 13 to 77 years of
      age, users of hearing aids. The HHIE-S/HHIA (Hearing Handicap Inventory for the
      Elderly Screening Version or for Adult) and APHAB (Abbreviated Profile of Hearing
      Aid Benefit) self-assessment questionnaires used with individuals without (Group
      1) and with complaints related to amplification characteristics (Group 2).
      RESULTS: we did not find significant differences between the HHIE-S/HHIA and
      APHAB groups; except in APHABs ease of communication item, where Group 1 seemed
      to benefit more. Moreover, we noticed a significant reduction in hearing
      disability with the use of hearing aids in favorable communication situations,
      noisy environments for both groups. CONCLUSION: these questionnaires proved to be
      valuable for predicting the difficulties faced by the users, and significant
      differences were found in favorable communication situations, where the group
      without complaints had the most benefit.

PMID- 18094809
TI  - Sensorineural hearing loss in chronic suppurative otitis media with and without
      cholesteatoma.
AB  - Sensorineural hearing loss (SNHL) related to chronic suppurative otitis media
      (CSOM) was studied to clarify the involvement of cholesteatomas in this context.
      AIM: to evaluate SNHL related to CSOM and its association with cholesteatomas,
      disease duration and patients ages. METHODS: Retrospective analysis of 115
      patients with CSOM with and without cholesteatoma submitted to surgical
      treatment. Inclusion criteria were active unilateral disease, normal
      contralateral ear and age below 60 years. RESULTS: The average age was 26.3
      years, 58 males and 57 females. The duration of ear disease was, in average, 12.4
      years. The average threshold of hearing was 40 dB in CSOM ear and 22 dB in the
      normal contralateral ear (P=0.002). CSOM with cholesteatoma occurred in 78 of 115
      cases. In the abnormal ear, SNHL was seen in 15 cases, being 6 cases of profound
      loss, that correlated with adjusted-age (P=0.003) and absence of cholesteatoma
      (P=0.01), but not with disease duration (P=0.458). CONCLUSION: SNHL occurred in
      13% of the patients with CSOM, and was correlated with older age, but not with
      the presence of cholesteatoma or longer duration of ear disease.

PMID- 18094810
TI  - Lombard's effect's implication in intensity, fundamental frequency and stability
      on the voice of individuals with Parkinson's disease.
AB  - Parkinson's disease affects the central nervous system resulting in voice quality
      alterations. It is typically resistant to drug therapy and often persists despite
      extensive behavioural speech and language therapy. Previous findings show that
      masking noise will produce a consistent increase in voice intensity in most
      normal individuals (Lombard's effect). AIM: we evaluated Lombard's effect's
      implication in intensity, fundamental frequency and stability on the voice of
      individuals with Parkinson's disease (N=17). MATERIAL AND METHODS: through
      acoustic analysis, we evaluated intensity alterations and fundamental frequency,
      before and after white masking noise 40, 70 and 90 dBSL intensities, as well as
      variations during each vocalization and compared with a control group (N=16).
      RESULTS: voice intensity varied according to masking intensity, tending to non
      linear increases in both groups and gender. Fundamental frequency varied, tending
      to non-linear increase in both groups and gender. Improvement stability occurred
      in fundamental frequency and vocal intensity. CONCLUSION: Lombard's effect
      increased intensity, fundamental frequency and improves voice stability on these
      patients. STUDY: clinical and experimental.

PMID- 18094811
TI  - Orbital complications of acute rhinosinusitis: a new classification.
AB  - Rhinosinusitis is a severe sickness and may have serious complications. Orbital
      complications happen more often, due to anatomical particularities and are lethal
      in 5% of patients. They vary from inflammatory signs to proptosis, loss of ocular
      motility and blindness. AIM: We propose a new classification of acute
      rhinosinusitis complications. METHODS: A review of 83 patients with CT scan and
      clinical reports. Patients were evaluated at HCFMRP-USP between 1995 and 2005 and
      were diagnosed with complicated rhinosinusitis. RESULTS: In sixty-six patients,
      were identified three types of orbital complications: orbital cellulitis (46.9%),
      subperiosteal abscess (40.9%) and orbital abscess (12.1%). Seventeen were
      considered as eyelid infections and excluded from this new classification system.
      CONCLUSIONS: The existing classifications of orbital complications, as Chandlers,
      do not consider the orbits anatomical characteristics and became obsolete after
      the development of the CT scan. This study proposes a new, more objective
      classification to guide the physician in establishing lines of conduct for each
      case.

PMID- 18094812
TI  - Endoscopic polipectomy with middle meatal antrostomy for antrochoanal polyp
      treatment.
AB  - Antrochoanal polyp (ACP) or Killian polyp is a benign nonatopic lesion of the
      maxillary sinus. Patients usually present nasal obstruction. Many surgical
      options for the treatment of ACPs have been suggested to minimize postoperative
      recurrence. The endoscopic nasal approach is a surgical option for maxillary
      intrasinusal resection of the polyp implantation through the maxillary ostium or
      middle meatal antrostomy, with lower morbidity when compared to other surgical
      approaches. AIM: To evaluate the rate of endoscopic antrochoanal polypectomy with
      middle meatotomy in the treatment of ACP. MATERIALS AND METHODS: Were evaluated
      by means of a retrospective study, 29 patients, who were diagnosed based on
      history, physical examination, computed tomography, and histological findings,
      treated between 1997 and 2004. The surgical approach was endoscopic polypectomy
      with middle meatotomy. RESULTS: Twenty-nine patients with ACP, 17(58.6%) were
      females and 12(41.4%) males, age range, 7-75 years (average of 27.55 years) were
      included in this study. The main symptom were nasal obstruction 24(82%), oral
      breathing 11(37.9%), snoring nine (31%), rhinorrhea 5(17%), epistaxis 2(6.9%),
      headache 2(6.9%), and drip one (3.4%). The association with atopy was found in
      nine (31%). The mean follow-up period was 17 months (3-63 months). Only two
      patients (6.9%) presented recurrence. CONCLUSION: The rate of recurrence obtained
      in our study is no different from literature data, even when compared with former
      and gold standard procedures.

PMID- 18094813
TI  - A brief history of otorhinolaryngolgy: otology, laryngology and rhinology.
AB  - Ears, nose and throat have intrigued humanity since immemorial times. Treatments
      for the larynx, the nose and the ear and also surgeries were practiced by Greek,
      Hindu and Byzantine doctors. In the 20th century clinical and surgical
      innovations were incorporated, thanks to new anesthesia techniques, antibiotics,
      radiology and new technologies. AIM AND METHOD: show the evolution of this
      science throughout the times, recognizing important persons in otology, rhinology
      and laryngology. RESULTS AND CONCLUSION: Understanding the evolutions in clinical
      and surgical anatomy, physiology, treatment modalities, and the personalities
      that lead to these advances is of great importance for the evolution of medical
      science. Otorhinolaryngology has a very rich history, with important
      collaborators and personalities in the history of medicine. The specialty was one
      of the first to use local anesthesia for procedures, pioneer in treatments with
      devices that recouped hearing and the use of microscopes in surgeries. Few
      medical specialties had suffered as many changes and scientific developments in
      these last decades as Otorhinolaryngology had, with the advantage of
      incorporating technologies such as endoscopy, radiology, microsurgery and
      information technology.

PMID- 18094814
TI  - Methods for studying mucociliary transport.
AB  - Mucociliary transport dysfunctions can impair the quality of life of patients
      suffering from chronic rhinossinusitis and lead to severe consequences such as
      alterations in respiratory physiology or even death as in cases of cystic
      fibrosis and primary ciliary dyskinesia. Therefore, it is crucial to understand
      the physiology of the mucociliary apparatus and how its components (cilia, mucus
      periciliary layer and its interaction) affect the clearance of respiratory
      secretions. AIMS: This paper aims to review and to discuss different techniques
      for studying mucociliary transport and their clinical and experimental
      applicability. CONCLUSIONS: The methods listed in this revision provide us with
      valuable information about different aspects of the mucociliary transport. Some
      of the methods listed are more suitable for clinical practice and present
      reproducible results. Others, show only applicability in experimental settings
      due to technical difficulties or financial limitations. However, it is important
      to emphasize that up to now there is no method that can evaluate ciliary beating
      frequency (CBF) in vivo and in situ. Such a method would become a valuable tool
      in the scientific scenario and in the clinical practice, supporting the diagnosis
      of ciliary dyskinesias and avoiding the use of invasive procedures to corroborate
      the clinical suspicion.

PMID- 18094815
TI  - Sudden deafness as a presenting symptom of acoustic neuroma: case report.
AB  - Vestibular schwannoma, also known as acoustic neurinoma, is the most frequent
      tumor of the cerebellopontine angle, and represents 9% of all intracranial
      tumors. CASE REPORT: The authors report a case of sudden deafness with unilateral
      tinnitus. The patients responded to therapy with Prednisone and Pentoxifylline
      after the diagnosis of acoustic neurinoma by imaging exams. DISCUSSION: Sudden
      deafness can be described as an intense and abrupt sensorineural loss. Usually it
      is higher than 30 dB at three or more frequencies and develops in less than three
      days. CONCLUSION: Investigation of the etiology of sudden deafness is extremely
      important to establish the adequate strategy for the case.

PMID- 18094816
TI  - Tongue necrosis in a patient with cranial arteritis.

PMID- 18094817
TI  - Pharyngeal cervical neurinoma: dysphonia and dysphagia.

PMID- 18094818
TI  - Osteoma of the middle ear.

PMID- 18094819
TI  - Primary tuberculosis of the parotid gland.

PMID- 18094820
TI  - Contribution to the feeding ecology of the banded puffer fish Colomesus psittacus
      (Tetraodontidae) in north Brazilian mangrove creeks.
AB  - Stomach contents were examined from 102 banded puffer, Colomesus psittacus
      (Tetraodontidae), caught from intertidal mangrove creeks at diurnal neap tides
      between June and September, 1997 (early dry season) near Braganca (north Brazil).
      The study found that C. psittacus were specialized predators of Cirripedia
      (Balanus spp.) and Brachyuran crabs (Uca spp., Pachygrapsus gracilis) (mean: 58
      and 38% by dry weight, respectively), emphasizing a short food chain in the
      mangrove system. Cirripedia and Brachyura dominated the diet in all size classes,
      however, the prey spectrum narrowed with fish size. The mean daily consumption of
      Cirripedia and Brachyura was 6.2% body weight of C. psittacus. On average C.
      psittacus consumed 100.3 g x ha(-1) x d(-1) of Cirripedia and 178.7 g x ha(-1) x
      d(-1) of Brachyura (wet weight). The predation on Brachyuran crabs--a significant
      driver of fluxes of organic matter and energy in the system--provides C.
      psittacus with an important ecological function in the mangrove food web. A plant
      animal interaction is proposed where C. psittacus exerts a mutually beneficial
      cleaning function on the Aufwuchs (Cirripedia and associated epibiota) of
      Rhizophora mangle stilt roots. Our results and those of other studies suggest
      that C. psittacus encounter optimum foraging conditions in the mangrove at high
      inundations at daylight (spring tide-day) whereas darkness and low inundations
      are linked to poor foraging conditions (neap tide-night). The C. psittacus
      resource could be used as an alternative income in the region in terms of i)
      sustainable catch and filet processing for exports to East Asia, ii) developing
      certified aquaculture methods for breeding puffers for the aquarium trade.

PMID- 18094821
TI  - Benthic Bacillariophyta of the Paripe River estuary in Pernambuco State, Brazil.
AB  - The aim of this study was to evaluate the benthic diatom composition from the
      estuary sediment in the Pernambuco State, based on 32 samples. Samples were
      collected monthly from September through December 1999 (dry period) and from
      April through July 2000 (rainy period) during four pre established sampling
      stations. Results indicated 19 families and 31 specific and infraspecific taxa.
      Eight new records were founded for Pernambuco State: Auliscus coelatus, Fallacia
      nummularia, Navicula algida, Plagiograma pulchellum, Terpsinoe americana,
      Triceratium antideluvianna and Tryblionella coarctata and one, Auliscus punctatus
      Bailey, in northeastern Brazil.

PMID- 18094822
TI  - Relief influence on the spatial distribution of the Atlantic Forest cover on the
      Ibiuna Plateau, SP.
AB  - Several studies suggest that, on a large scale, relief conditions influence the
      Atlantic Forest cover. The aim of this work was to explore these relationships on
      a local scale, in Caucaia do Alto, on the Ibiuna Plateau. Within an area of about
      78 km(2), the distribution of forest cover, divided into two successional stages,
      was associated with relief attribute data (slope, slope orientation and
      altitude). The mapping of the vegetation was based on the interpretation of
      stereoscopic pairs of aerial photographs, from April 2000, on a scale of
      1:10,000, while the relief attributes were obtained by geoprocessing from
      digitalized topographic maps on a scale of 1:10,000. Statistical analyses, based
      on qui-square tests, revealed that there was a more extensive forest cover,
      irrespective of the successional stage, in steeper areas (>10 degrees) located at
      higher altitudes (>923 m), but no influence of the slope orientation. There was
      no sign of direct influence of relief on the forest cover through environmental
      gradients that might have contributed to the forest regeneration. Likewise, there
      was no evidence that these results could have been influenced by the distance
      from roads or urban areas or with respect to permanent preservation areas. Relief
      seems to influence the forest cover indirectly, since agricultural land use is
      preferably made in flatter and lower areas. These results suggest a general
      distribution pattern of the forest remnants, independent of the scale of study,
      on which relief indirectly has a strong influence, since it determines human
      occupation.

PMID- 18094823
TI  - Description of two new sympatric species of the genus Hisonotus Eigenmann and
      Eigenmann, 1889, from upper Rio Tapajos, Mato Grosso state, Brazil (Pisces:
      Ostariophysi: Loricariidae).
AB  - Two new species of the genus Hisonotus are described from the upper Rio Tapajos
      basin, Mato Grosso State, Brazil. They are small species, growing up to about
      30.0 mm SL, having the scapular bridge wide and totally exposed or having a small
      median pair of arrector fossae, and the abdomen completely covered with large
      plates in adult specimens (about 23.0 mm SL). They are distinguished from their
      congeners by the following combination of characters: Hisonotus chromodontus has
      20-40 reddish-brown tipped premaxillary teeth, and 15-38 on the dentary bones;
      2324 plates on the longitudinal series; a prominent large dark brown lateral
      stripe extending from the tip of the snout to the caudal blotch; transversal dark
      brown bars very inconspicuous or absent. Hisonotus luteofrenatus has a moderate
      number (12-28) of hyaline or slightly yellow-tipped premaxillary teeth, and 9-26
      on the dentary bones; 25-26 plates on the longitudinal series; a characteristic
      yellow line extending from the anterior part of each orbit, over the inferior
      nostril, both converging to the tip of the snout.

PMID- 18094824
TI  - Psychotria hoffmansegiana (Willd ex Roem. & Schult.) Mull. Arg. and Palicourea
      marcagravii st. Hil. (Rubiaceae): potential for forming soil seed banks in a
      brazilian Cerrado.
AB  - The germinability of artificially buried Psychotria hoffmansegiana and Palicourea
      marcagravii seeds in Cerrado soil was tested, with the aim of evaluating whether
      dispersed seeds may be able to form a soil seed bank. The assays were carried out
      at a Cerrado Reserve in Sao Paulo State, Brazil. Seed samples were placed in
      nylon bags and buried at two different depths and in two different sites. Samples
      were periodically exhumed and germination tests were performed with both exhumed
      and dry stored seeds. In general, soil storage favoured seed survival and
      germination when compared to dry stored seeds. The seed germination was little
      affected by soil depth and by burial environment. Seeds of both species remained
      viable for at least 13 months, considering the time lapse between the collection
      and the end of the germination tests. It was suggested that both species can
      potentially form a persistent soil seed bank in Cerrado.

PMID- 18094825
TI  - Study of the social hierarchy and territoriality of Calomys callosus Rengger,
      1830 (Rodentia: Cricetidae).
AB  - The genus Calomys comprises a lot of species distributed throughout South
      America. The species C. callosus Rengger, 1830 occur in Brazil, been often used
      in laboratory experiments. This work involved a study of aggressive behavior and
      dominance, which are aspects related to hierarchy and territoriality, among C.
      callosus males kept in a laboratory. The establishment of a hierarchy was
      observed, with the dominant animals controlling the space, food and water, while
      the remaining animals were confined to a restricted space. The intensity of
      aggression and variations in the number of attacks declined over time as a result
      of the formation of the hierarchy. No wounds were observed, probably due to the
      ritualistic nature of the attacks.

PMID- 18094826
TI  - The hydraulic management of the Barra Bonita reservoir (SP, Brazil) as a factor
      influencing the temporal succession of its fish community.
AB  - The temporal succession of fish communities allows evaluating the environmental
      conditions and the adaptation capacity of the fish species to anthropogenic
      stress in reservoirs. The fish community at Barra Bonita reservoir was sampled in
      two different periods of the year (dry and rainy) and in three different areas of
      the reservoir (fluvial, transition, and lentic). The species list was compared to
      another four lists, trying to detect the transformations of the fish community
      for the last 15 years. In order to evaluate the adaptation of the present fish
      community to the hydraulic management of reservoir, the trophic and reproductive
      structures were studied. Temporal succession analysis shows little change in fish
      richness of the communities. The number of fish species varies between 23 and 39
      for a total of 68 registered species. From this, 27 can be considered constant,
      14 accessory and 27 accidental; the main differences observed were for
      Anostomidae, Loricariidae and Characidae families. In relation to the hydraulic
      management, we found a fish community stabilized and adapted to environmental
      stress. This is characterized by the dominance of small-sized fish species of
      opportunistic diet and high reproductive compensation (r-strategists). The
      overlap of biological cycles of the most abundant species with the reservoir
      level fluctuations points to the period from September to March-April as critical
      for reproductive success and only the species with partial reproductive strategy
      or parental care are best succeeded. These results, interpreted in the context of
      the reservoir aging process, indicate that Barra Bonita reservoir is entering a
      transition phase, between the colonization and aging stages.

PMID- 18094827
TI  - Edaphic and arboricolous oribatid mites (Acari; Oribatida) in tropical
      environments: changes in the distribution of higher level taxonomic groups in the
      communities of species.
AB  - We analysed the community of oribatid mites in 25 environments of northern Brazil
      and one in a rain forest in Peru, encompassing fauna sampled on natural and
      artificial (nylon-mesh bags) substrata, from primary and secondary forests,
      caatinga, savannahs, flooded forests, bark and epiphytes of trees, and
      polyculture. A hundred and forty six species are definitively identified from a
      total of 444 taxa. To determine changes in the community, we took as a basis of
      comparison the species dominance of Lower Oribatida vs. Oppioidea and Lower
      Oribatida vs. Poronota. Even considering the different periods in which the
      inventories were realized and the different sampling methodology compared, the
      partition of the species of Oribatid mite in larger groups shows tendencies
      indicating partition of species dominance among the environments studied, showing
      that they differed in their suitability as habitats for the Oribatid mite
      community, mainly in respect to the Lower Oribatida, Oppioidea and Poronota
      composition. These tendencies should be explored in more detail as more becomes
      known about the species composition in each environment.

PMID- 18094828
TI  - The feeding activity of Colossoma macropomum larvae (tambaqui) in fishponds with
      water hyacinth (Eichhornia crassipes) fertilizer.
AB  - Analysis of macrophyte water hyacinth (Eichhornia crassipes) as an organic
      fertilizer of Colossoma macropomum (tambaqui) larvae in ponds is provided. Water
      hyacinth produce an organic fertilizer at the ratio of 100 g x m(-2) in tambaqui
      ponds. Two groups of 5,000 larvae were transferred to two fishponds with and
      without water hyacinth fertilizer and reared until day 43. The fertilized pond
      evidenced more plankton abundance during the entire production period when
      compared with the control pond (P < 0.001). The phytoplankton community in the
      pond was not significantly different than in gut contents (P > 0.05) in both
      ponds (with and without organic fertilizer). Fish larvae failed to show any
      preference or selectivity in relation to the different algae (P > 0.01) in the
      pond, but exhibited high ingestion selectivity for zooplankton (P < 0.05).
      Application of fertilizer increased (P < 0.05) the abundance of phytoplankton and
      zooplankton in the treatment pond. Since water hyacinth fertilizer is quite cheap
      and easily available, it may be conveniently used to enhance fish yield in ponds.

PMID- 18094829
TI  - Spatial distribution by Canistropsis microps (E. Morren ex Mez) Leme
      (Bromeliaceae: Bromelioideae) in the Atlantic rain forest in Ilha Grande,
      Southeastern Brazil.
AB  - Canistropsis microps (Bromeliaceae: Bromelioideae) is an endemic species of
      Atlantic rain forest areas in Rio de Janeiro State, which are very abundant in
      not very disturbed forests in Ilha Grande, on the southern coast of the State. In
      this study, we analyzed the vertical and horizontal distribution patterns of the
      species in an area of rain forest with little evidence of disturbance at Vila
      Dois Rios, Ilha Grande, relating the patterns to sunlight in the microhabitat. We
      also identified the types of substrate used by the species and the rate of
      asexual reproduction. Canistropsis microps had high densities (estimated at
      84,425 rosettes/ha), and has an aggregated distribution (Id = 2.86). About 80% of
      the rosettes were generated by clonal growth, whereas less than 20% were produced
      from seedlings. Most of the rosettes were found on straight tree trunks (DBH > 50
      cm). There was a significant inverse correlation between the incidence of
      sunlight in the habitat and the abundance of individuals. Rosettes were found up
      to a maximum height of 9.5 m, but most occured between 1.5 and 5.5 m, where light
      varied from 25 to 50 micromol x s(-1) x m(-2). We conclude that vertical and
      horizontal distribution patterns in C. microps may be partially explained by the
      occurrence of appropriate substrate, an intensity of sunlight favorable to the
      development of the species and to a high rate of vegetative reproduction.

PMID- 18094830
TI  - Temporal and spatial fluctuations of phytoplankton in a tropical coastal lagoon,
      southeast Brazil.
AB  - Spatial and temporal variability of the phytoplankton community in the tropical
      coastal Imboassica lagoon, an environment naturally isolated from the ocean by a
      narrow sandbar, was analysed every two weeks for 19 months by sampling three
      sites. During this study, the lagoon received direct input of marine water three
      times, resulting in remarkable salinity, nutrient concentrations and
      phytoplankton biomass variations in both temporal and spatial aspects. The
      phytoplankton biomass presented relatively low values ranging, on average, from
      0.54 mg x L(-1) in the station closest to the sea (station 1) to 1.34 mg x L(-1)
      in the station close to a macrophyte bank (station 3). Diatoms and cryptomonads
      dominated in stations 1 and 2 (located relatively close to station 1, yet
      receiving the runoff of domestic sewage), and euglenoids, cryptomonads and
      dinoflagellates at station 3. Stations 1 and 2 usually presented the same
      dominant species but station 2 presented a higher phytoplankton biomass. On the
      other hand, station 3 showed more similar results concerning phytoplankton
      biomass with station 2, however the dominant species were usually different. The
      high fluctuations of salinity and the reduced nutrient availability are pointed
      out as the main factors structuring the dynamics of the phytoplankton community
      at the Imboassica lagoon.

PMID- 18094831
TI  - Feeding ecology of a nocturnal invasive alien lizard species, Hemidactylus
      mabouia Moreau de Jonnes, 1818 (Gekkonidae), living in an outcrop rocky area in
      southeastern Brazil.
AB  - We studied in fieldwork, the feeding ecology of a Hemidactylus mabouia population
      from southeastern Brazil throughout one year in a region with marked climatic
      seasonality. A sampling of availability of arthropods in the environment was
      carried out, which evidenced that the availability of food resources influenced
      the composition of the diet of H. mabouia. There were no seasonal differences on
      diet composition, which may be due to the relatively constant availability on
      prey throughout the year. In general, this population can be classified as
      generalist and opportunistic regarding diet. There was a high food niche overlap
      among juveniles and adults, although juvenile lizards tend to eat higher number
      of prey (but in lower volume) when compared to adult lizards. The ability to
      exploit a wide array of prey in an efficient way, maintaining a positive
      energetic balance, may be a factor determining the efficiency of this exotic
      species to occupy invaded areas.

PMID- 18094832
TI  - Total-Hg and organic-Hg in Cephalopholis fulva (Linnaeus, 1758) from inshore and
      offshore waters of NE Brazil.
AB  - To investigate whether source proximity or bioavailability is the major factor
      controlling both Hg concentration and Hg speciation in marine fishes, total- and
      organic-Hg content in muscle and liver tissues from different populations of
      Cephalopholis fulva (pirauna) from inshore and offshore waters of the Brazilian
      northeastern coast were analyzed. Average total-Hg in muscle (104 ng x g(-1)
      w.w.) and liver (2,865 ng x g(-1) w.w.) tissues, as well as organic-Hg
      concentrations in muscle (169 ng x g(-1) w.w.) and liver (1,038 ng x g(-1) w.w.),
      were much higher in the offshore population of C. fulva than in the inshore ones.
      In the inshore population total-Hg and organic-Hg average concentrations in
      muscle tissue were similar and reached only 49 ng x g(-1) w.w., while in liver
      they reached 412 ng x g(-1) w.w. for total-Hg and 180 ng x g(-1) w.w., for
      organic-Hg. Concentrations of both Hg species in the two populations were higher
      in liver than in muscle. The average percentage contribution of organic-Hg to the
      total Hg content was higher in muscle (98-100%) than in liver (42-53%), but
      similar between the two populations. Total-Hg and organic-Hg concentrations in
      muscle and liver from the offshore population showed significant (P < 0.05)
      positive correlation with fish length. However, in the inshore population only
      the total-Hg and organic-Hg in muscle tissues correlate significantly with fish
      size. Although the coastal environments are enriched in total Hg relative to open
      waters, the significant higher Hg concentrations in the offshore population of C.
      fulva and the significant correlation found between organic-Hg in liver with fish
      size suggest higher bioavailability of Hg in offshore waters relative to inshore
      ones.

PMID- 18094833
TI  - Macroinvertebrate fauna associated with Pistia stratiotes and Nymphoides indica
      in subtropical lakes (south Brazil).
AB  - This study was carried out at the Biguas and Polegar lakes, both small
      environments but at different successional stages. The main objective was to
      characterize the macroinvertebrate community associated to the aquatic macrophyte
      stand in each lake in order for this community, the environmental conditions and
      their water quality to interact. The samples were taken in 2003. The abiotic
      variables of N and P totals, the temperature, electrical conductivity, pH and
      dissolved oxygen, as well as the determined clorophyll a concentration were
      measured. Macroinvertebrates were sampled with a 500 micro mesh size net,
      separated under a stereomicroscope and identified at the lowest possible
      taxonomic level, and their densities were shown as the number of individuals per
      100 g of macrophyte dry weight. The Shannon-Wiener Diversity Index (H'), Pielou
      evenness (J), frequency of occurrence, abundance and taxa richness were
      calculated for each invertebrate community. The Lago dos Biguas is undergoing a
      process of eutrophication and during the study presented a large Pistia
      stratiotes stand. The Lago Polegar is oligotrophic and had only a small
      Nymphoides indica bankwe. The macrophyte associated invertebrate communities in
      each lake were considered significantly different (p < 0.05). Sixty seven taxa
      were found for the Lago dos Biguas and 32 for the Lago Polegar. For both lakes,
      most of the taxa were considered rare, with a low dominance in a few months. The
      taxa with highest densities at Lago dos Biguas were Chironomidae, Daphniidae and
      Cyclopidae, and Oligochaeta, Chironomidae and Coenagrionidae for Lago Polegar.

PMID- 18094834
TI  - Karyotype composition of some rodents and marsupials from Chapada Diamantina
      (Bahia, Brasil).
AB  - The Chapada Diamantina (CD) is located in Bahia State, between 11-14 degrees S
      and 41-43 degrees W, being part of the Serra do Espinhaco. The occurrence of
      different habitats and transition areas permits an interesting mammal fauna
      composition, with species from different biomes living in sympatry. Species of
      Didelphimorphia and Rodentia are important members of mammal communities in
      almost all different habitats, and morphological and cytogenetic characters are
      important for a correct identification of most of these species. In this work 258
      specimens of small mammals from the orders Didelphimorphia (six genera and six
      species) and Rodentia (two families, five Sigmodontinae tribes, nine genera and
      11 species) were collected during the whole field work (44 nights with traps).
      Chromosome preparations were obtained from 145 specimens from the species:
      Marmosops incanus, Gracilinanus microtarsus, Monodelphis domestica, Akodon aff.
      cursor, Necromys lasiurus, Cerradomys sp., Oligoryzomys fornesi, O. nigripes, O.
      rupestris, Calomys expulsus, Rhipidomys macrurus, Wiedomys pyrrhorhinus and
      Thrichomys inermis. Didelphis albiventris, Micoureus demerarae, Thylamys karymii
      and Nectomys sp. were identified by morphological characters. Most analyzed
      specimens do not show karyotype variation. However, numerical chromosomic
      variation was found in two individuals of Akodon aff. cursor (2n = 15) and in one
      individual of Cerradomys sp. (2n = 51). Structural variation in karyotype was
      observed in seven individuals of Cerradomys sp., showing one additional pair of
      metacentric chromosomes.

PMID- 18094835
TI  - Influence of temperature on microsporidia infections in a natural population of
      Simulium pertinax Kollar, 1832 (Diptera; Simuliidae).
AB  - During the studies involving the correlation between the water temperature of the
      breeding site of Simulium pertinax larvae and the infection prevalence by
      microsporidia, developed in the Andorinhas river, Mage, RJ, weekly samples of
      blackfly larvae were taken within a two-year period (2001-2002 and 2003-2004),
      and it was noticed that the infections by Amblyospora sp. were more prevalent
      when compared to infections by Polydispyrenia sp. in larvae. It was also observed
      that the infections do not follow the same pattern, since the genus Amblyospora
      was recorded almost every month during the study with the exception of December,
      2001. In the results of correlation between the environmental water temperature
      and the microsporidia infection rates, it was observed that for the first period
      studied, there was a high negative correlation, while during the second period
      there was absence correlation. On the other hand, the Amblyospora sp. infection
      rates prove that the correlation was high and significant in the first period,
      but was not significant in the second sampling period and Polydispyrenia sp.
      showed absence correlation in both periods.

PMID- 18094836
TI  - Hatching rates of resting eggs of 'Cladocera' (Crustacea; Branchiopoda) at a
      tropical bay, Brazil.
AB  - The aim of this study was to determine the development time of embryos and to
      estimate the hatching rates of resting eggs of cladocerans found in the sediment
      of Guanabara Bay, Rio de Janeiro, Brazil, under experimental conditions. Eggs
      were sorted by species (Penilia avirostris--Sididae; Pleopis polyphemoides and
      Pseudevadne tergestina--Podonidae) and incubated at a temperature of 25 degrees
      C, salinity 35 and photoperiod 12 hours light/ 12 hours dark. Hatching rates were
      about 38% for Pseudevadne tergestina and 28% for Pleopis polyphemoides. Embryos
      of resting eggs of Penilia avirostris developed comparatively slowly (hatching
      after 86 days of incubation), with a hatching rate of only 5%. It was observed
      that development and hatching of resting eggs of marine cladocerans suggest that
      pulses of recruitment may exist, thus contributing to the rapid appearance and
      maintenance of planktonic populations of these crustaceans in Guanabara Bay.

PMID- 18094837
TI  - Blood parasites, total plasma protein and packed cell volume of small wild
      mammals trapped in three mountain ranges of the Atlantic Forest in Southeastern
      Brazil.
AB  - A study of blood parasites in small wild non-flying mammals was undertaken in
      three areas of the Atlantic Forest in Southeastern Brazil: Serra de Itatiaia, RJ,
      Serra da Bocaina, SP and Serra da Fartura, SP, from June 1999 to May 2001. A
      total of 450 animals (15 species) were captured in traps and it was observed in
      15.5% of the blood smears the presence of Haemobartonella sp. and Babesia sp. in
      red blood cells. There was no statistically significant difference between
      parasited and non-parasited specimens regarding total plasma protein, packed cell
      volume and body weight, which strongly suggests that these specimens might be
      parasite reservoirs.

PMID- 18094838
TI  - Nest and nest-site reuse within and between breeding seasons by three neotropical
      flycatchers (Tyrannidae).
AB  - Nest and or nest site reuse within and between breeding seasons was reported by
      the Euler's Flycatcher (Lathrotriccus euleri), the Sepia-capped Flycatcher
      (Leptopogon amaurocephalus) and the Gray-hooded Flycatcher (Mionectes 
      rufiventris) in forest fragments from southeastern Brazil. Nest and or nest site
      reuse between some years was frequent within a single breeding season by the
      Sepia-capped Flycatcher. Nest reuse, however, was not related to nesting success
      in the previous breeding attempt. Nest turnover rates (movement to a new site
      between years) were low for L. amaurocephalus, intermediate for L. euleri and
      high for M. rufiventris.

PMID- 18094839
TI  - Reproduction of Pirapitinga do Sul (Brycon opalinus Cuvier, 1819) in the Parque
      Estadual da Serra do Mar-Nucleo Santa Virginia, Sao Paulo, Brazil.
AB  - The objective of the study was to characterize seasonally and locally the
      reproduction of Pirapitinga do Sul (Brycon opalinus). The study area included
      three rivers (Paraibuna, Ipiranga, and Grande) in the Santa Virginia Unit of the
      Serra do Mar State Park, State of Sao Paulo, Brazil. Breeding occurred in spring,
      summer, and autumn. The L(50) and the L(100) of this species were 16 to 18 cm and
      26 to 28 cm, respectively. Spawning was total, with synchronous development in
      two groups. The size of mature oocytes was 1,346.4 microm, reaching a maximum of
      2,570.4 microm, with a mean fecundity of 9,190.5 oocytes. This species has
      external fertilization, is non-migratory, and lacks parental care of the young.
      Preservation of the Pirapitinga do Sul depends, in great part, on maintaining
      water quality, preservation of the riverine forests, and access to breeding
      areas.

PMID- 18094840
TI  - Reproductive cycle of Macrobrachium amazonicum females (Crustacea, Palaemonidae).
AB  - Macrobrachium amazonicum is considered a favorite Brazilian species of freshwater
      prawn for cultivation as a result of its quick development and because it is easy
      to maintain in captivity. The aim of this work is to describe the sexual cycle
      stages and determine maturation age of the female M. amazonicum, which was
      collected monthly from June, 2002 to May, 2003 in the Jaguaribe River, Itaicaba,
      Ceara. A monthly sample of water was also collected to determine the following
      parameters: temperature, dissolved oxygen, pH and salinity. A monthly sample of
      females was selected among the individuals caught, to determine the total weight
      (W(T)), carapace length (L( C)) and abdomen+telson length (L(A+T)) and to
      register the number of non-ovigerous females (NOF) and ovigerous females (OF).
      Determining ovarian maturation stages of M. amazonicum was done in a laboratory
      by observing macroscopic characters such as coloring, size, location and
      appearance of ovarians examined by transparent carapace. The first maturation age
      was determined from the relative frequency of the total length (L(T)) of young
      and adult females. The environmental parameters of the Jaguaribe River did not
      hold any influence in the number of individuals collected. A total of 1,337
      prawns were sampled, 513 males (38.4%) and 824 females (61.6%). The proportion
      between males and females in the studied population was of 1:1.6. Among the
      collected females, 492 (50.7%) did not carry eggs in their abdomens (NOF) and 332
      (40.3%) carried eggs in their abdomens (OF). There was no record of intact
      females. Non-ovigerous females with mature ovaries were recorded throughout all
      the months of collection. The female ovaries were classified as immature (IM),
      rudimentary (RU), intermediary (IN) and mature (M). M. amazonicum females reach
      their first sexual maturity between 4.5 and 5.5 cm of total length.

PMID- 18094841
TI  - Yield per recruit of the pacu Piaractus mesopotamicus (Holmberg, 1887) in the
      pantanal of Mato Grosso do Sul, Brazil.
AB  - Among the several fish species comercially exploited at the Pantanal of Mato
      Grosso do Sul, the "pacu" (Piaractus mesopotamicus) stands as one of the most
      important. Information regarding its exploitation level is necessary for the
      proper management of its stocks. Between 1996 and 1997 data on total length of
      the pacu were collected on a monthly basis from specimens caught by professional
      and sport fishers in the municipality of Corumba. These data were used to
      estimate growth parameters and to assess the exploitation level for this species,
      applying the Beverton and Holt yield per recruit model. Length frequency
      analysis, carried out with the software FISAT (ELEFAN), was used to estimate
      growth parameters: 1996: L(infinity) = 87.20 cm; K = 0.34 year(-1); phi(')=3.41;
      C = 0.74; WP = 0.81; Longevity = 8.40 years; and 1997: L(infinity) = 86.50 cm; K
      = 0.34 year(-1); phi(')=3.40; C = 0.60; WP = 0.80; Longevity = 8.40 years. The
      value for t(0) is -0.363 years for mean values of L(infinity) and k. The weight
      length relationship, calculated from data derived from experimental fisheries
      carried out in 1999 and 2000, is described by the equation: W = 0.048LF(2.835).
      Estimated mortalities and survival rates were: 1996: Z = 1.51 year(-1); M = 0.62
      year(-1); F = 0.89 year(-1); S = 21.9%; and 1997: Z = 1.65 year(-1); M = 0.63
      year(-1); F = 1.02 year(-1); S = 19.1%. The yield per recruit analysis showed the
      following values: F(Present) = 0.96 year(-1); F(max) = 0.67 year(-1) ; F(0.1) =
      0.51 year(-1) (for L(c) = 26.7 cm). These results suggest that the pacu is
      overexploited in the area, so that restrictive measures are in need to manage the
      pacu fisheries.

PMID- 18094842
TI  - Canopy phenology of a dry forest in western Brazil.
AB  - Dry forests are common, although highly threatened in the Neotropics. Their
      ecological processes are mostly influenced by rainfall pattern, hence their
      cycles exhibit contrasting phases. We studied the phenology of canopy trees in a
      primary dry forest in Western Brazil in the foothills of the Urucum mountain
      chain, in order to improve our knowledge on the functioning of these poorly-known
      forests. Leaf shedding started in the early dry season and was massive in the
      latter part of this period. Most leaf loss occurred in dry hills, while wet
      valleys remained evergreen. Anemochorich and autochorich species predominated in
      dry hills, presumably due to their tolerance to dry conditions and enhanced
      exposition to winds, which favour diaspores removal and dispersal. Conversely,
      zoochorich species dominated the wet valleys. Flowering was intense in the late
      dry season, the driest period of the year, while fruiting was massive just after
      the onset of rains, as well as flushing. Therefore, most flowering was unrelated
      to wet conditions, although such an abiotic factor, potentially, triggered the
      major fruiting episode, widely comprised by zoochorich species. Anemochorich and
      autochorich species flowered and fruited in the course of the long dry season.
      The contrasting environmental conditions present in the hills and valleys
      determine the arrangement of a mosaic in which patches of zoochorich and
      evergreen trees alternate with patches of non zoochorich and highly deciduous
      species. Consequently, species with such syndromes exhibited marked flowering and
      fruiting patterns, accordingly to the pronounced seasonality.

PMID- 18094843
TI  - Occurrence of Pachycrepoideus vindemmiae (Rondani, 1875) (Hymenoptera:
      Pteromalidae) as a parasitoid of Megaselia scalaris (Loew, 1866) (Diptera:
      Phoridae) in Brazil.

PMID- 18094844
TI  - The first record of amphibians as paratenic hosts of Serpinema larvae (Nematoda;
      Camallanidae).

PMID- 18094845
TI  - Parasitoid Hymenoptera collected during the diurnal and nocturnal periods in
      Itumbiara, Goias.

PMID- 18094846
TI  - Treefrog Dendropsophus elegans (Wied-Neuwied, 1824) (Anura: Hylidae) as a meal to
      Otostigmus tibialis Brolemann, 1902 (Chilopoda: Scolopendridae) in the Tropical
      Rainforest in southeastern Brazil.

PMID- 18094847
TI  - Occurrence of Pseudodiaptomus gracilis (F. Dahl, 1894), Copepoda, Calanoida in
      amazonian fresh waters.

PMID- 18094848
TI  - Corpus callosum index: a practical method for long-term follow-up in multiple
      sclerosis.
AB  - Rather than acute inflammation, long-standing multiple sclerosis (MS) course is
      hallmarked by relentless axonal loss and brain atrophy, both with subtle clinical
      expression and scarcely visible on conventional MRI studies. Brain atrophy
      imaging has sophisticated methodological requirements, not always practical and
      accessible to most centers. Corpus callosum (CC) is a major inter-hemispheric
      white matter bundle, grossly affected by long term MS and easily assessed by MRI.
      To determine whether a practical imaging method can reliably follow presumed
      axonal loss in patients with progressive MS, we designed a 5-year prospective
      open label study, enrolling 128 consecutive patients (75 relapsing-remitting (RR)
      and 53 secondary-progressive (SP)), on regular immunomodulatory therapy compared
      to control group, formed by 23 patients with MRI considered normal. On a
      conventional best mid-sagittal T1W, CC index (CCI) was obtained by measuring
      anterior, medium and posterior segments of CC, normalized to its greatest
      anteroposterior diameter using an orthogonal semi-automated linear system. CCI
      was measured at baseline and at least once yearly. Results were plotted intra
      individually; baseline values were used as reference. At baseline, CCI was able
      to distinguish SP patients from RR and controls, and on follow-up, despite some
      overlap, demonstrated a progressive reduction from baseline on both RR and SP
      groups compared to controls. From the third year on, difference between SP and RR
      patients reached statistical significance, which did not correlated with
      disability measured by EDSS. So, a corpus callosum index proved practical and
      feasible to longitudinally demonstrate morphometric callosal changes with
      potential to be used as a tool for long-term follow-up, mostly in SP patients.

PMID- 18094849
TI  - Association analysis between a VNTR intron 8 polymorphism of the dopamine
      transporter gene (SLC6A3) and obsessive- compulsive disorder in a Brazilian
      sample.
AB  - Family, twin and segregation analysis have provided evidences that genetic
      factors are implicated in the susceptibility for obsessive-compulsive disorder
      (OCD). Several lines of research suggest that the dopaminergic system may be
      involved in the pathophysiology of OCD. Thus, the aim of the present study was to
      investigate a possible association between a polymorphism located in intron 8 of
      the dopamine transporter gene (SLC6A3) and OCD in a Brazilian sample composed by
      208 patients and 865 healthy controls. No statistical differences were observed
      in allelic and genotype distributions between cases and controls. No association
      was also observed when the sample was divided according to specific phenotypic
      features such as gender, presence of tic disorders, co-morbidity, and age at
      onset of obsessive-compulsive symptoms (OCS). Our results suggest that the intron
      8 VNTR of the SLC6A3 investigated in this study is not related to the
      susceptibility for OCD in our Brazilian sample.

PMID- 18094850
TI  - Cognitive function assessment in idiopathic Parkinson's disease.
AB  - Idiopathic Parkinson's disease (PD) is characterized by reduced nigrostriatal and
      cortical dopaminergic influence, with changes in movement and, subsequently,
      behavioral and cognitive disturbances. We studied cognitive impairment in
      Parkinson's disease by assessing a group of 30 idiopathic Parkinson's disease
      patients with an average age of 64.23 years (PG group) and compared our findings
      with those for a control group of 30 patients (CG group). All the patients were
      submitted to the following assessments: motor function, using the UPDRS; staging,
      using the Hoehn-Yahr scales (PG group only); depression, using the Montgomery
      Asberg scale; attention impairment; verbal fluency (FAR and animals); cognitive
      function, using the Mini Mental State Examination; visuospatial and executive
      functions; and clock drawing. In addition to altered motor function in PD
      patients, we found statistically significant differences between PD patients and
      controls in terms of cognitive function, verbal, executive and visuospatial
      functions, and attention deficits. Depression was more prevalent in the PG group.

PMID- 18094851
TI  - Mesial temporal sclerosis in children.
AB  - Mesial temporal sclerosis is the most frequent cause of drug-resistant temporal
      lobe epilepsy but has a satisfactory response to surgery, and is considered
      infrequent in children. OBJECTIVE: To evaluate the clinical, electrographic and
      radiological spectrum of the disease in children. METHOD: Retrospective study by
      review of charts of 44 children with a diagnosis of mesial temporal sclerosis on
      magnetic resonance imaging, attended at the "Hospital das Clinicas" of the
      University of Sao Paulo Faculty of Medicine. RESULTS: Febrile seizure was
      identified in the history of 54% of the patients. Injuries at the left side
      predominated in patients with schooling difficulties (p=0.049), in those with
      first seizures between six months and five years (p=0.021) and in those with
      complex febrile seizure (p=0.032). Thirteen patients were submitted to surgery
      and of these, eight remained without seizures. CONCLUSION: Febrile seizure may be
      related in a more direct way to the presence of left-side mesial temporal
      sclerosis.

PMID- 18094852
TI  - Motor learning processes: an electrophysiologic perspective.
AB  - The goal of the present study was to investigate electrophysiologic, qEEG,
      changes when individuals were exposed to a motor task. Subjects brain electrical
      activity was analyzed before and after the typewriting training task. For the
      neurophysiological variable asymmetry, a paired t-test was performed to compare
      each moment, pre and post-task, in the beta bands. The findings showed a change
      for the qEEG variable in each scalp site, F3/F4; C3/C4 and P3/P4. These results
      suggest an adaptation of pre-frontal, sensory-motor and parietal cortex, as a
      consequence of the typewriting training.

PMID- 18094853
TI  - The effects of bromazepam on the early stage of visual information processing
      (P100).
AB  - The early stages of visual information processing, involving the detection and
      perception of simple visual stimuli, have been demonstrated to be sensitive to
      psychotropic agents. The present study investigated the effects of an acute dose
      of bromazepam (3 mg), compared with placebo, on the P100 component of the visual
      evoked potential and reaction time. The sample, consisting of 14 healthy subjects
      (6 male and 8 female), was submitted to a visual discrimination task, which
      employed the "oddball" paradigm. Results suggest that bromazepam (3 mg) impairs
      the initial stage of visual information processing, as observed by an increase in
      P100 latency.

PMID- 18094854
TI  - Brain tumors in the first three years of life: a review of twenty cases.
AB  - OBJECTIVE AND METHOD: To review the clinical and neuropathological findings as
      well as the type of therapy and outcome in 20 infants under 3 years-old with
      central nervous system (CNS) tumor. They were treated at the Department of
      Neurology, "Hospital das Clinicas" University of Sao Paulo Medical School, from
      January 1997 to May 2001. RESULTS: Astrocytoma was the most common histological
      type (n=7), followed by ependymoma (n=3), medulloblastoma (n=2),
      craniopharyngioma (n=2) and desmoplastic ganglioglioma (n=2). The location of the
      tumor was predominantly supratentorial. Mean follow-up time was 20.2 months with
      recurrence in 7 cases. For each type of tumor we have emphasized the treatment
      currently recommended. CONCLUSION: Although follow-up time is not sufficient for
      analyzing survival, a trend of improvement in prognosis was noted, compared to
      another series of cases from our Institution that had been evaluated before 1990.

PMID- 18094855
TI  - The history of spinocerebellar ataxia type 10 in Brazil: travels of a gene.
AB  - The authors report the history of spinocerebellar ataxia 10 (SCA10), since its
      first report in a large Portuguese-ancestry family with autosomal dominant pure
      cerebellar ataxia, till the final identification of further families without
      Mexican ancestry. These families present a quite different phenotype from those
      SCA10 families described in Mexico.

PMID- 18094856
TI  - Pure neural leprosy: steroids prevent neuropathy progression.
AB  - Multidrug therapy (MDT), with rifampicin, dapsone, and clofazimine, treats
      leprosy infection but is insufficient in arresting or preventing the nerve damage
      that causes impairments and disabilities. This case-series study evaluates the
      benefits of the combined use of steroids and MDT in preventing nerve damage in
      patients with pure neural leprosy (PNL). In addition to MDT, 24 patients (88%
      male aged 20-79 years, median=41) received a daily morning dose of 60 mg
      prednisone (PDN) that was gradually reduced by 10 mg during each of the following
      5 months. PNL was clinically diagnosed and confirmed by nerve histopathology or
      PCR. A low prevalence (8.3%) of reaction was observed after release from
      treatment. However, most of the clinical parameters showed significant
      improvement; and a reduction of nerve conduction block was observed in 42% of the
      patients. The administration of full-dose PDN improved the clinical and
      electrophysiological condition of the PNL patients, contributing to the
      prevention of further neurological damage.

PMID- 18094857
TI  - Ultrastructural study of the lateral ventricle choroid plexus in experimental
      hydrocephalus in Wistar rats.
AB  - Hydrocephalus is one of the most frequent and complex neurological diseases
      characterized by the abnormal buildup of cerebrospinal fluid (CSF) in the
      ventricles of the brain, due to an altered CSF dynamics. To detect possible
      ultrastructural alterations of the lateral ventricles choroid plexus (responsible
      for the CSF production), rats seven days after birth were submitted to an
      intracisternal injection of 20% kaolim (hydrated aluminum silicate) for the
      hydrocephalus induction. Twenty-eight or 35 days after injection, injected
      animals and respective controls were processed for observation under a
      transmission electron microscopy. Alterations found: presence of concentric cell
      membrane fragments, larger number of primary and secondary lysossomes, vacuoles,
      and cytoplasmic vesicles, and an enlargement of the intercellular space and
      between the basolateral interdigitation of the choroid epithelium. The
      alterations observed are probably associated to an increase of the ventricular
      pressure, inducing morpho-functional effects on the choroid plexus integrity.

PMID- 18094858
TI  - Evaluation of the neuroprotective effect of ketoprofen on rats submitted to
      permanent focal brain ischemia.
AB  - OBJECTIVE: To study the neurobehavioral, biochemical and histopathological
      consequences of permanent focal brain ischemia, and the putative neuroprotective
      action of ketoprofen. METHOD: One-hundred-and-three Wistar rats divided into
      groups A and B were respectively submitted to 48 hours and 15 days of ischemia.
      Each group was divided into 4 subgroups: ischemic not treated, ischemic treated,
      sham not treated, and sham treated. Ischemic animals had the left middle cerebral
      artery coagulated. Ketoprofen was administered to treated subgroups 15 minutes
      before arterial coagulation (manipulation in the sham group). RESULTS:
      Exploratory activity and defecation were reduced in all ischemic animals in the
      first postoperative days and constant histopathological changes were observed in
      each group. The total brain glutamate levels were higher in treated animals 48
      hours after surgery. CONCLUSION: No clear parallelism among behavioral,
      biochemical and histopathological findings was observed. Ketoprofen demonstrated
      no neuroprotective effect on the behavioral or histopathological aspects of focal
      permanent brain ischemia.

PMID- 18094859
TI  - Variable fMRI activation during two different language tasks in a patient with
      cognitive delay.
AB  - Functional MRI produces a more accurate localization of the language areas for
      epilepsy surgery purpose, but requires the patient's cooperation. We report a 34
      year-old woman with mental retardation who underwent two different verbal fluency
      tasks, category and word naming. We found a strong activation of Broca's area in
      the most difficult task. We suggest that a multi-task fMRI study could be
      successful in patients with cognitive delay.

PMID- 18094860
TI  - Basal encephalocele associated with morning glory syndrome: case report.
AB  - The basal encephaloceles refer to rare entities and they correspond to herniation
      of brain tissue through defects of skull along the cribiform plate or the
      sphenoid bone. A rare morning glory syndrome, with characteristic retinal defect
      has been reported in association with basal encephaloceles. Hypophysis hormonal
      deficiencies may occur. We accounted for a pituitary dwarfism with delayed
      diagnosed transsphenoidal encephalocele associated with morning glory syndrome,
      showing the alterations found in retinography, computed tomography and magnetic
      resonance imaging.

PMID- 18094861
TI  - Giant cavernoma of the orbit: clinical and surgical considerations.
AB  - Cavernous hemangiomas of the orbit are benign, hamartomatous, vascular lesions,
      more frequent in middle-aged women, representing the most common benign primitive
      neoplasm of the orbit. Several therapeutic modalities and surgical approaches
      have been described, in order to preserve the normal orbital structures. We
      describe the case of a patient with a volumous orbital cavernoma, approached by a
      fronto-orbito-zigotomy. A review on diagnostic modalities and surgical approaches
      is also presented.

PMID- 18094862
TI  - Tectal glioblastoma.
AB  - Brain stem gliomas are a heterogeneous group of neoplasms arising mostly in
      paediatric patients. Tectal plate gliomas represent a particular type of brain
      stem tumours usually with a benign, indolent clinical course, presenting with
      signs of raised intracranial hypertension due to supra-tentorialhydrocephalous
      caused by aqueductal stenosis. Seldom high-grade lesions arise in this location
      with tremendous therapeutic implications. When a malignant tumour is clinically
      and radiographically suspected a biopsy should be performed to obtain
      histological confirmation. Treatment is then planned in a case-by-case basis. We
      present the case of a glioblastoma of the tectal plate in a 22 years-old woman
      operated upon by a supracerebellar-infratentorial approach.

PMID- 18094863
TI  - Meningiomas of pineal region in children.
AB  - Meningiomas are uncommon tumors in children and either more rarely encountered in
      the pineal region. We report two cases of meningioma of the pineal region in
      children. One of these cases was a five years-old girl and the other a one year
      old boy. No specific clinical presentation or tomographic examinations findings
      was identified before treatment, suggestive of a diagnosis of meningioma. The
      clinical and laboratory features were very similar to the most common tumors of
      the pineal region. Prior to the surgery, the histology of these tumors was not
      suspected. Both patients underwent direct surgery and complete removal was
      achieved by a suboccipital transtentorial approach. The tumors originated from
      velum interpositum in both cases. At the follow up, one case presented with
      recurrence six years later, and she underwent a reoperation with total resection
      without morbidity. Long-term follow up presented no other recurrences.

PMID- 18094864
TI  - Bilateral ptosis and supranuclear downgaze paralysis.
AB  - The purpose of this article is to highlight an uncommon combination of
      supranuclear downward gaze paralysis with bilateral eyelid ptosis in a 53-year
      old man with a radiation induced midbrain tumor and to discuss the aspects
      regarding the centers and pathways that mediate supranuclear vertical gaze
      movements.

PMID- 18094865
TI  - Cerebellar degeneration and immune thrombocytopenic purpura associated with human
      immunodeficiency virus infection (HIV).
AB  - Cerebellar disorders associated with HIV infection are usually caused by
      opportunistic infections, central nervous system lymphoma, and toxic effects of
      medicines, nutritional and metabolic disorders, and cerebrovascular disease. We
      present an unusual association of cerebellar degeneration and immune
      thrombocytopenic purpura in a 28-years-old woman HIV infected. An autoimmune
      aetiology is likely.

PMID- 18094866
TI  - Endovascular treatment of a basilar artery dissecting aneurysm.
AB  - Basilar artery (BA) dissecting aneurysms pose difficulties to treatment because
      both bleeding and thrombosis can happen in the same patient, clinical course is
      unpredictable and high morbidity is usual. We report the case of a 37-year-old
      woman with a BA aneurysm probably caused by arterial dissection, presenting
      embolic and hemorrhagic complications. The aneurysm was submitted to endovascular
      treatment with stenting and coil embolization. Clinical and radiological results
      were excellent and no complications were observed, suggesting that BA stenting
      and coil embolization may be a safe and effective treatment for this condition.

PMID- 18094867
TI  - Benign fasciculations responsive to gabapentin.
AB  - Fasciculations are symptoms present in a broad spectrum of conditions, ranging
      from normal manifestations to motor neuron diseases. They also represent the main
      picture of benign fasciculation syndrome. We report a case of such syndrome: a 48
      years-old woman complaining about fasciculations for three decades who remained
      with the symptoms even after the compensation of a disclosed hyperthyroidism. The
      introduction of gabapentin rendered control of her fasciculations. The available
      data in the literature about the therapeutic approaches for fasciculations are
      revised, as long as the rare reports of evolution from patients with "benign"
      fasciculations to cases of amyotrophic lateral sclerosis, underlining the
      importance of following the patients with fasciculations.

PMID- 18094868
TI  - Cerebral abscess caused by Serratia marcescens in a premature neonate.
AB  - BACKGROUND: Cerebral abscesses are extremely rare in neonates. Serratia
      marcescens is an unusual cause of sepsis and neurological spread is especially
      ominous. PURPOSE: To report the case of a 34-week neonate who developed this rare
      condition and to discuss diagnostic and therapeutic measures. CASE REPORT: A 34
      week male neonate sequentially developed respiratory distress syndrome, early
      sepsis and necrotizing enterocolitis; later cultures revealed S. marcescens.
      After deterioration, a cerebral abscess became evident, which revealed S.
      marcescens. Clinical improvement ensued after high-dose amikacin and meropenem.
      CONCLUSION: Clinical signs are often non-specific. Proper diagnostic measures,
      neurosurgical consultation and aggressive antibiotic therapy are essential for
      these high-risk neonates.

PMID- 18094869
TI  - Cerebellar abscess by Gemella morbillorum in a patient with inter-atrial
      communication.
AB  - Gemella morbillorum, a commensal of the oropharynx, upper respiratory, urogenital
      and gastrointestinal tract is rarely associated with infections in humans.
      However, an increasing number of infectious processes in different locations have
      been reported. Cerebral abscesses caused by these bacteria are extremely uncommon
      with only four cases previously described in the literature. We present the case
      of a cerebellar abscess by Gemella morbillorum in a 50 year-old man with inter
      atrial communication dealt by surgical excision and antimicrobial therapy.

PMID- 18094870
TI  - Pyridoxine-dependent epilepsy initially responsive to phenobarbital.
AB  - Pyridoxine-dependent epilepsy is a rare autosomal recessive disorder
      characterized by recurrent seizures that are not controlled by anticonvulsant
      medications but remits after administration of pyridoxine. We report on a 30 day
      old girl who presented with seizures during the first day of life, initially
      responsive to anticonvulsant therapy, which remitted within two weeks. Seizures
      were characterized as multifocal myoclonic jerks of upper and lower limbs
      associated with buccal-lingual oral movements and eyelid blinking. Laboratory and
      neuroimaging studies were normal. Electroencephalographic record demonstrated a
      abnormal background activity with high-voltage epileptic discharges and a burst
      suppression pattern. The seizures ceased after oral administration of pyridoxine,
      but recurred after withdrawal, confirming the diagnosis.

PMID- 18094871
TI  - Atypical subacute sclerosing panencephalitis: case report.
AB  - Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory disorder
      of the central nervous system with both poor prognosis and high mortality. The
      disease has been related to a persistent and aberrant measles virus infection and
      no effective treatment has been available. We report a case of SSPE with atypical
      features including seizures at onset and a fulminant course in a 8 years-old boy
      who had been previously immunized against measles.

PMID- 18094872
TI  - Spontaneous acute subdural hematoma contralateral to an arachnoid cyst.
AB  - Arachnoid cysts (AC) are extra-cerebral cerebrospinal fluid collections of
      unknown origin. They correspond to 1% of all intracranial nontraumatic space
      occupying lesions and appear more frequently in the middle fossa (50%). More than
      25% of these cysts are incidental findings and the majority of patients are
      asymptomatic. Seizures, intracranial hypertension signs, neurological deficits,
      macrocrania, developmental delay and bulging of the skull are the main signs and
      symptoms of the lesion. AC rupture and bleeding are rare, usually occurring in
      young adults and associated with trauma. The risk of hemorrhage does not exceed
      0.04% / year. We describe the case of a ten-year-old boy who presented with acute
      signs of intracranial hypertension secondary to a spontaneous acute subdural
      hematoma, contralateral to an AC of the middle fossa. Three factors were
      significant in this case: signs and symptoms occurred spontaneously; the presence
      of an acute subdural hematoma exclusively contralateral to the AC; successful
      outcome of the conservative treatment.

PMID- 18094873
TI  - Horner's syndrome after blunt cervical and chest trauma: case report.
AB  - Horner's syndrome is the triad of miosis, ptosis, and anhidrosis, resulting from
      disruption of the sympathetic pathways. This article describes an uncommon case
      of Horner's syndrome in a 22-year-old man after blunt trauma to the neck and
      chest without carotid artery dissection. The patient was brought to the emergency
      service after motorcycle fall. Neurologic examination revealed a patient
      presenting the score 15 at Glasgow Coma Scale. The left eyelid was 1-2 mm lower
      than the right. Carotid Doppler and angiotomography were undertaken and revealed
      no abnormalities of the carotid artery. CT disclosed a mediastinal hematoma
      extending to the left apex, compressing the left sympathetic chain. The
      understanding of this clinical entity may help the surgeon to make a better
      differential diagnosis in trauma patients in whom prompt diagnosis is critical to
      establish the correct treatment.

PMID- 18094874
TI  - Rathke's cleft cyst and partial feet adactyly: an unusual association.
AB  - A 53 year-old woman presented a recurrent bifrontal headache of 2 years duration
      and bilateral progressive visual disturbance. The clinical and neurological
      examination showed a bilateral feet adactyly and bitemporal hemianopsia. The
      brain MRI demonstrated a Rathke's cleft cyst. The patient was operated by a
      transnasal endoscopic approach. It seems that this unusual association has never
      been described before.

PMID- 18094875
TI  - [A neurocomputational model for the thalamocortical loop: towards a better
      understanding of attention deficit hyperactivity disorder].
AB  - BACKGROUND: Inattention symptoms observed in patients with attention deficit
      hyperactivity disorder (ADHD) are mostly related to a hypoactivity in the
      mesocortical dopaminergic pathway. However, mesothalamic dopaminergic variations
      also affect the attentional control, and possibly lead to attention alterations
      in ADHD. PURPOSE: Elaborating a neurocomputational model from biochemical
      knowledge of mesocortical and mesothalamic dopamine systems, to investigate how
      different levels of mesothalamic dopamine influence the thalamocortical loop,
      leading to some attention deficits observed in ADHD. METHOD: First, we model
      physiological properties of thalamic neurons with a set of mathematical
      equations. Next, we simulate computationally the modeled thalamocortical loop
      under different levels of mesothalamic dopamine, and also the mesocortical
      dopaminergic decrease. RESULTS: Low levels of mesothalamic dopamine hinders the
      attentional shift and, high levels of such neuromodulator lead to distraction.
      When such alterations occur together with a decrease in the mesocortical dopamine
      level, the attention deficit turns into incapacity of perceiving environmental
      stimuli, due to a no winner competition between low activated thalamic areas.
      Inattention in ADHD also has its origins in dopaminergic disturbs throughout the
      mesothalamic pathway, which enhance a high focusing or do not allow the attention
      focus consolidation. CONCLUSION: In ADHD, the inattention is related to
      dopaminergic alterations that are not restricted to the mesocortical system.

PMID- 18094876
TI  - [Spontaneous carotid and vertebral arteries dissection in a multiethnic
      population].
AB  - Spontaneous dissection of the carotid and vertebral arteries (SDCVA) is
      considered a rare cause of stroke, particularly in countries with multiethnic
      population. The objective was to evaluate the clinical and neuroimaging features
      of patients with SDCVA from a multiethnic population. Sixty-six patients
      diagnosed with SDCVA were studied at two tertiary hospitals at Sao Paulo. An
      initial questionnaire was completed and patients were followed prospectively.
      Among the patients studied, 82% were caucasian, 53% were male and the average age
      was 41.7 years old. The most frequent cardiovascular risk factors found were
      systemic hypertension and tobacco use. Other aspects evaluated were history of
      previous migraine, initial treatment and prognosis. In conclusion, although the
      population studied was multiethnic, there was a marked predominance of
      caucasians. The analysis of clinical and neuroimaging data from patients with
      SDCVA allows a better understanding of the disease, leading to an earlier
      diagnosis and more appropriate treatment.

PMID- 18094877
TI  - [Pediatric glioblastoma: a clinicopathological study of 12 cases with p53 protein
      immunohistochemistry].
AB  - Glioblastoma is one of the most lethal central nervous system (CNS) primary
      tumors. Although significant progress, only few analysis have been made in
      pediatric glioblastoma, which are less common and have worse prognosis than in
      adults. To evaluate gender, site, age, survival, and immunohistochemistry to p53,
      we selected cases of pediatric glioblastoma of "CNS Tumors Database in Curitiba",
      1987-2003 and of the Hospital Municipal Jesus, Rio de Janeiro, 1970-1988. Twelve
      tumors were included. The age ranged from up to 12 years (median 7). There were 7
      females and 5 males. The median survival was 7.9 months. Location was: cerebral
      hemispheres (58.4%), mesencephalon and brainstem (33.3%) and one case in the
      cerebellum. Immunostained to p53 in 9 (75%) cases. In conclusion, glioblastoma
      behaves similarly in children and adults. It is rare in children, affects both
      cerebral hemispheres more than brainstem and cerebellum and shows strong
      immunohistochemistry to p53.

PMID- 18094878
TI  - [Hippocampal microsurgical anatomy regarding the selective
      amygdalohippocampectomy in the Niemeyer's technique perspective and preoperative
      method to maximize the corticotomy].
AB  - The deep knowledge of hippocampal microsurgical anatomy is paramount in epilepsy
      surgery. One of the most used techniques is those proposed by Niemeyer. PURPOSE:
      To describe the hippocampal anatomy in detail and to present a technique in which
      preoperative anatomical points in MRI are identified to guide the corticotomy.
      METHOD: Microsurgical dissections were performed in twenty brain hemispheres and
      eight cadaveric heads to identify temporal lobe and hippocampus structures.
      Thirty two patients with drug-resistant temporal lobe epilepsy underwent a
      selective amygdalohippocampectomy with Niemeyer's technique being measured three
      preoperative MRI preoperative distances to guide the corticotomy. RESULTS: The
      hippocampus was divided in head, body and tail and its microsurgical anatomy
      described in detail. The MRI measurements are presented and discussed.
      CONCLUSION: The knowledge of the complex anatomy of the hippocampus can be
      achieved in a three-dimensional way during microsurgical dissections. The
      preoperative MRI measurement is a reasonable guide to perform temporal
      corticotomy in Niemeyer's technique.

PMID- 18094879
TI  - [Immunohistochemical staining of the astrocytic expression of glial fibrillary
      acidic protein and vimentin in the central nervous system of dogs with canine
      distemper].
AB  - Considering that many aspects involved in the pathogenesis of the central nervous
      system (CNS) demyelinating diseases are still poorly understood and that
      astrocytes seem to mediate such processes, this study analyzed the participation
      of astrocytes in the demyelinating processes of CNS by using immunohistochemical
      staining of two astrocytic proteins--glial fibrillary acidic protein (GFAP) and
      vimentin (VIM)--comparing samples of cerebellum and brainstem from eight dogs
      with canine distemper and from two healthy dogs, from different breeds and ages
      varying from 1 to 4 years old. Histological sections were submitted to the avidin
      biotin-peroxidase indirect method of immunohistochemical staining (ABC) and the
      astrocytic reactivity, observed in light microscopy, was quantified in a computer
      system for image analysis. It was possible to notice, on most of the sections
      from sick animals, degenerative lesions that indicate demyelination. The
      immunostaining for GFAP and VIM was more intense on animals with canine
      distemper, specially around the ventricules and near degenerated sites. There was
      no significant difference between the immunostaining (GFAP and VIM) of animals
      with canine distemper with and without inflammatory infiltrate of the cerebellar
      white matter. The increased immunoreactivity of astrocytes for GFAP and the VIM
      reexpression in injured areas indicate the astrocytic involvement on nervous
      tissue response to the demyelinating lesions induced by the canine distemper
      virus (CDV) in the CNS.

PMID- 18094880
TI  - [Prevalence of attention deficit hyperactivity disorder and its comorbidities in
      a sample of school-aged children].
AB  - Attention deficit hyperactivity disorder (ADHD) is a frequent condition in school
      age children and commonly presents in comorbidity with other psychiatric
      diseases. In Brazil, there are few studies concerning non-clinical samples.
      PURPOSE: The present study aims to calculate the prevalence of this disorder and
      its comorbidities in a sample of school-age children. METHOD: Cross-sectional
      analytic study was conducted on a non-clinical sample of children and adolescents
      registered in 2003 in the elementary school of the Federal University of Rio de
      Janeiro. A screening questionnaire was used and parents of those possible
      affected children were invited for a clinical structured interview. RESULTS: The
      prevalence of ADHD was 8.6%. Comorbidities were present in 58% of the cases and
      oppositional-defiant disorder was the most common, found in 38.5%. CONCLUSIONS:
      The prevalence of ADHD and its comorbidities in this sample is similar to that
      observed in the literature.

PMID- 18094881
TI  - [Changes in the electroencephalogram alpha band during visual and kinesthetic
      motor imagery].
AB  - This study aims at statistically assessing the differences in alpha band power,
      particularly in the vicinity of the alpha peak (BPA), during motor imagery (MI).
      Multi-channel EEG (occipital and parietal regions) was acquired at rest condition
      (ESP) and MI kinesthetic (MIC) and visual (MIV) modalities from right-handed male
      subjects (18-40 years), 15 athletes (experienced volleyball players) and 15 non
      athletes. The Revised Movement Imagery Questionnaire indicated no differences
      between groups or MI modalities, but athletes imagine themselves more clearly
      than non-athletes during MI. The power within BPA reduces in both groups, but
      greater in MIC than in MIV. The cortical activation was similar in both
      hemispheres of non-athletes but more pronounced in left hemisphere of athletes,
      mainly in MIC. The findings suggest that MI reduces alpha activity according to
      individual knowledge of real execution of motor task and MI modalities.

PMID- 18094882
TI  - [Ketogenic diet for the treatment of refractory epilepsy].

PMID- 18094886
TI  - Molecular diversity of serial Cryptococcus neoformans isolates from AIDS patients
      in the city of Sao Paulo, Brazil.
AB  - Despite highly active anti-retroviral therapy, cryptococcal meningoencephalitis
      is the second most prevalent neurological disease in Brazilian AIDS patients,
      being frequently a defining condition with several episodes. As knowledge of
      Cryptococcus neoformans isolates in the same episode is critical for
      understanding why some patients develop several episodes, we investigated the
      genotype characteristics of C. neoformans isolates in two different situations.
      By pulsed field gel electrophoresis and random amplified polymorphic DNA
      analysis, 54 isolates from 12 patients with AIDS and cryptococcosis were
      analyzed. Group 1 comprised 39 isolates from nine patients with a single episode
      and hospitalization. Group 2 comprised 15 isolates from three patients with two
      episodes and hospitalizations. Except for three patients from group 1 probably
      infected with a single C. neoformans isolate, the other nine patients probably
      were infected with multiple isolates selected in different collection periods, or
      the infecting isolate might have underwent mutation to adapt and survive the host
      immune system and/or the antifungal therapy. However, the three patients from
      group 2 presented genetic diversity among isolates collected in both
      hospitalizations, possibly having hosted the initial isolate in both periods.
      These data, emphasize that Cryptococcus diversity in infection can contribute to
      strategies of treatment and prevention of cryptococcosis.

PMID- 18094887
TI  - Rickettsia infection in five areas of the state of Sao Paulo, Brazil.
AB  - This study investigated rickettsial infection in animals, humans, ticks, and
      fleas collected in five areas of the state of Sao Paulo. Eight flea species
      (Adoratopsylla antiquorum antiquorum, Ctenocephalides felis felis, Polygenis
      atopus, Polygenis rimatus, Polygenis roberti roberti, Polygenis tripus,
      Rhopalopsyllus lugubris, and Rhopalopsyllus lutzi lutzi), and five tick species
      (Amblyomma aureolatum, Amblyomma cajennense, Amblyomma dubitatum, Ixodes
      loricatus, and Rhipicephalus sanguineus) were collected from dogs, cats, and
      opossums. Rickettsia felis was the only rickettsia found infecting fleas, whereas
      Rickettsia bellii was the only agent infecting ticks, but no animal or human
      blood was shown to contain rickettsial DNA. Testing animal and human sera by
      indirect immunofluorescence assay against four rickettsia antigens (R.
      rickettsii, R. parkeri, R. felis, and R. bellii), some opossum, dog, horse, and
      human sera reacted to R. rickettsii with titers at least four-fold higher than to
      the other three rickettsial antigens. These sera were considered to have a
      predominant antibody response to R. rickettsii. Using the same criteria, opossum,
      dog, and horse sera showed predominant antibody response to R. parkeri or a very
      closely related genotype. Our serological results suggest that both R. rickettsii
      and R. parkeri infected animals and/or humans in the studied areas.

PMID- 18094888
TI  - Case-control study of factors associated with chronic Chagas heart disease in
      patients over 50 years of age.
AB  - A case-control study on chronic Chagas heart disease (CCHD) was carried out
      between 1997 and 2005. Ninety patients over 50 years of age were examined for
      factors related to (CCHD). Fourty-six patients (51.1%) with Chagas heart disease
      (anomalous ECG) were assigned to the case group and 44 (48.9%) were included in
      the control group as carriers of undetermined forms of chronic disease. Social,
      demographic (age, gender, skin color, area of origin), epidemiological
      (permanence within an endemic zone, family history of Chagas heart disease or
      sudden death, physical strain, alcoholism, and smoking), and clinical (systemic
      hypertension) variables were analyzed. The data set was assessed through single
      variable and multivariate analysis. The two factors independently associated with
      heart disease were age--presence of heart disease being three times higher in
      patients over 60 years of age (odds ratio, OR: 2.89; confidence interval of 95%:
      1.09-7.61)--and family history of Chagas heart disease (OR: 2.833, CI 95%: 1.11
      7.23). Systemic hypertension and gender did not prove to hold any association
      with heart disease, as neither did skin color, but this variable showed low
      statistical power due to reduced sample size.

PMID- 18094889
TI  - First record of molluscs naturally infected with Angiostrongylus cantonensis
      (Chen, 1935) (Nematoda: Metastrongylidae) in Brazil.
AB  - Seeking the identification of Angiostrongylus cantonensis as a potential
      etiological agent of three clinical cases of eosinophilic meningitis, mollusc
      specimens were collected in the state of Espirito Santo, Brazil. The snails were
      identified as Sarasinula marginata (45 specimens), Subulina octona (157),
      Achatina fulica (45) and Bradybaena similaris (23). Larvae obtained were
      submitted to polymerase chain reaction and restriction fragment length
      polymorphism diagnosis. Their genetic profile were corresponded to A.
      cantonensis. Rattus norvegicus experimentally infected with third-stage larvae,
      developed menigoencephalitis, and parasites became sexually mature in the lungs.
      Additionally, larvae obtained from A. fulica snails, from Sao Vicente, state of
      Sao Paulo, also showed genetic profiles of this nematode. This is the first
      record of Brazilian molluscs infected with this nematode species.

PMID- 18094890
TI  - Drug-eluting stent in diabetes.

PMID- 18094891
TI  - Prevalence of uterine synechia after abortion evacuation curettage.
AB  - CONTEXT AND OBJECTIVE: Intrauterine adhesion (IUA) is a possible complication of
      uterine curettage following abortion. Because IUA is an important cause of
      infertility, some investigators have been advocating its inclusion in the routine
      investigational workup after every abortion curettage procedure. The aim of this
      study was to evaluate the uterine cavity of patients subjected to abortion
      curettage, in order to ascertain the prevalence of IUA and its association with
      social and clinical factors. DESIGN AND SETTING: This was a cross-sectional study
      at the Human Reproduction Unit, Department of Obstetrics and Gynecology,
      Universidade Estadual de Campinas (Unicamp). METHODS: A total of 109 women were
      enrolled. The investigators searched the records of Unicamp's hospital for
      patients who had been subjected to uterine curettage following abortion. The
      hysteroscopy was performed 3 to 12 months after the curettage. The correlations
      between patients' characteristics and the prevalence of IUA were assessed by
      means of chi-squared and Fisher's exact test calculations. RESULTS: The
      prevalence of IUA was 37.6%. The number of previous abortions and curettage
      procedures did not correlate with the presence of IUA. Most of the women (56.1%)
      presented IUA grade I. CONCLUSIONS: In the present study, 37.6% of the women
      subjected to curettage following abortion had IUA, which was mostly mucous and
      grade I. None of the demographic and clinic characteristics evaluated were found
      to be associated with IUA. From this study, there is no firm evidence to justify
      carrying out routine diagnostic hysteroscopy following abortion evacuation.

PMID- 18094892
TI  - Impact of supervised physiotherapeutic pelvic floor exercises for treating female
      stress urinary incontinence.
AB  - CONTEXT AND OBJECTIVE: Urinary incontinence is a public health problem that
      affects more than 200 million people worldwide. Stress incontinence is the most
      prevalent type. Pelvic floor muscle exercises have been used for treating it,
      although there is no consensus regarding their application. The aim of this study
      was to compare the results from treating female stress urinary incontinence with
      pelvic floor muscle exercises with or without physiotherapist supervision. DESIGN
      AND SETTING: This was a randomized, prospective, controlled trial in the
      Urogynecology and Vaginal Surgery Sector, Universidade Federal de Sao Paulo.
      METHODS: Forty-four women were randomized to be treated for stress urinary
      incontinence with pelvic floor exercises for three consecutive months, into two
      groups: one with and the other without physiotherapist supervision. They were
      evaluated before and after treatment using a quality-of-life questionnaire, pad
      test, micturition diary and subjective evaluation. Descriptive analysis was used
      to evaluate the population. The homogeneity of the two groups was evaluated using
      the Kruskal-Wallis and Chi-squared tests. The success of the two groups after
      treatment was evaluated using the Wilcoxon test. RESULTS: The supervised group
      showed statistically greater improvement in the pad test, micturition diary and
      quality of life than did the control group. In the subjective evaluation, only
      23.8% of the control group patients were satised with their treatment. In the
      supervised group, 66.8% of patients did not want any other treatment. CONCLUSION:
      Supervised pelvic floor muscle exercises presented better results in objective
      and subjective evaluations than did unsupervised exercises.

PMID- 18094893
TI  - Chronic use of diazepam in primary healthcare centers: user profile and usage
      pattern.
AB  - CONTEXT AND OBJECTIVE: Chronic use of benzodiazepines is frequent in general
      practice. The aim of this study was to describe the usage pattern and profile of
      chronic users of diazepam who had been consuming this drug for a minimum of
      thirty-six months continuously. DESIGN AND SETTING: This was a descriptive study
      (survey and clinical assessment) at five primary healthcare centers in Campinas,
      Brazil. METHODS: Psychotropic drug control books revealed 48 eligible patients.
      Among these, 41 were assessed by means of the Schedule for Clinical Assessment in
      Neuropsychiatry (SCAN), the Hospital Anxiety and Depression scale (HAD) and a
      questionnaire on usage pattern. RESULTS: Most patients were women (85.4%). The
      patients' mean age was 57.6 years, and they were from the social strata C (39%),
      D (54%) and E (7%). The mean length of diazepam consumption was 10 years. The
      patients presented a lack of prescription compliance and had made frustrated
      attempts to stop using the drug. 55.5% said their doctor had never given any
      guidance on the effects of the drug. According to SCAN, 25 patients (61%)
      suffered from depressive disorders; only 12 cases of benzodiazepine dependence
      were detected by this instrument. CONCLUSION: There is a need to improve the
      detection and treatment of mental disorders, as well as to prevent inappropriate
      prescription and use of benzodiazepines. Diazepam dependence has distinctive
      characteristics that make it undetected by SCAN.

PMID- 18094894
TI  - Effect of oral contraceptive with and without associated estriol on ultrasound
      measurements of breast fibroadenoma: randomized clinical trial.
AB  - CONTEXT AND OBJECTIVE: Fibroadenomas are the most common benign tumors of the
      female breast. The aim of this study was to evaluate the proliferative activity
      of breast fibroadenoma as shown by ultrasound measurements, following
      administration of oral contraceptives with and without associated estriol. DESIGN
      AND SETTING: This was a randomized, double-blind, placebo-controlled clinical
      trial carried out in the Mastology Sector, Department of Gynecology, Universidade
      Federal de Sao Paulo. METHODS: We studied 33 women with fibroadenomas. Ten were
      placed in group 1 and took an oral contraceptive consisting of levonorgestrel and
      ethinyl estradiol together with placebo material in the same capsule, for four
      consecutive cycles with a seven-day interval between them. The other 23 patients
      constituted group 2 and took the oral contraceptive as above together with
      estriol in the same capsule, in the same way as done by the group 1 patients. We
      took ultrasound measurements of their tumors (in three dimensions) before and
      after the intake of medication. At the end of the study, all the patients had
      their tumors removed by surgery. RESULTS: We observed decreased fibroadenoma
      width among the users of oral contraceptives with placebo, and this decrease was
      statistically significant. In the other group, we did not observe any changes (in
      width, length or height). CONCLUSION: The results confirm that estriol may block
      the protective effect of oral contraceptives on fibroadenomas, since we observed
      decreased fibroadenoma width among the group 1 patients but not the group 2
      patients.

PMID- 18094895
TI  - Sociodemographic and clinical characteristics, causal factors and evolution of a
      group of patients with chronic urticaria-angioedema.
AB  - CONTEXT AND OBJECTIVE: Chronic urticaria-angioedema is a common, multiple-cause
      complaint. The aim was to investigate the sociodemographic and clinical
      characteristics, causal and aggravating factors and evolution of urticaria
      angioedema. DESIGN AND SETTING: This was a descriptive prospective study carried
      out at the Dermatology outpatient clinic of Faculdade de Medicina de Botucatu,
      Universidade Estadual Paulista (Unesp). METHODS: A total of 125 patients with
      chronic urticaria-angioedema were evaluated to obtain sociodemographic data,
      anamnesis, dermatological and general clinical data and laboratory data,
      emphasizing causal and aggravating factors and complaint evolution. RESULTS:
      Chronic urticaria-angioedema occurred mainly in females (mean age: 35 years), but
      also in men (mean age: 32 years). White color and living in urban areas also
      predominated. There was no preferential time for symptoms to appear, and
      nighttime was the most commonly reported time for clinical worsening. Around half
      of the patients had urticaria associated with angioedema. There were no
      associated factors in most of the cases, and stress was the most commonly
      reported aggravating factor. The cause was ascertained in 37.6% of our cases. The
      mean duration of follow-up was 11.7 months. Around 60% of the patients evolved
      with the problem under control, 32% improved, 9% had no change in dermatological
      condition and only one patient worsened. CONCLUSIONS: Chronic urticaria
      angioedema was more common among middle-aged women. It is a long-term disease,
      and its cause was explained in about one-third of the patients. Half of the
      patients presented disease control after treatment lasting an average of
      approximately one year.

PMID- 18094896
TI  - Primary testicular non-Hodgkin's lymphoma--a review article.
AB  - Primary testicular non-Hodgkin's lymphoma was first described as a clinical
      entity in 1866. It is a rare disease and accounts for 1% of all non-Hodgkin's
      lymphoma, 2% of all extranodal lymphomas and 5% of all testicular neoplasms. It
      is the most common testicular tumor in males between sixty and eighty years of
      age. Testicular non-Hodgkin's lymphoma is unique in its high incidence of
      bilateral involvement (8-38%), and it is also the most common bilateral
      testicular tumor. Testicular non-Hodgkin's lymphoma has a predilection for
      spreading to non-contiguous extranodal sites, especially the central nervous
      system. Advanced-stage disease is usually managed with doxorubicin-based
      chemotherapy. For early-stage disease, opinion is divided regarding systemic
      chemotherapy following orchidectomy. The high incidence of spreading, especially
      to the central nervous system, leads to advocacy of the use of central nervous
      system prophylaxis with intrathecal chemotherapy. Prospective multicenter trials
      incorporating a large number of patients may lead to better guidelines for
      optimal management of this subtype of non-Hodgkin's lymphoma.

PMID- 18094897
TI  - Comparative analysis of the prevalence of the glutathione S-transferase (GST)
      system in malignant and benign thyroid tumor cells.
AB  - CONTEXT AND OBJECTIVE: When null, the mu and theta genes of the glutathione S
      transferase system (GSTM1 and GSTT1, respectively) are related to malignant
      tumors affecting the lungs, colon, prostate, bladder and head and neck. In the
      thyroid, the appearance of cancer has been correlated with deletion of these
      genes. The aim of this study was to compare the frequencies of these genes in
      patients with benign and malignant tumors of the thyroid gland. DESIGN AND
      SETTINGS: This was a cross-sectional clinical trial carried out in the Head and
      Neck Surgery Division, Faculdade de Medicina da Santa Casa de Sao Paulo. METHODS:
      Samples of thyroid tissue were collected from 32 patients and divided into two
      groups: benign tumor (A) and malignant tumor (B). After DNA extraction, the genes
      were amplified using PCR. RESULTS: The B group presented four cases of positive
      genotyping for both genes, seven positive for GSTT1 and negative for GSTM1, two
      negative for GSTT1 and positive for GSTM1, and only one case of double negative.
      The A group showed 11 cases with positive genotyping for both genes and none with
      the double negative genotype. CONCLUSION: In this study, there was no
      relationship between the presence of the GSTT1 and GSTM1 genes and the benign and
      malignant thyroid tumors.

PMID- 18094898
TI  - Perianal squamous cell carcinoma with high-grade anal intraepithelial neoplasia
      in an HIV-positive patient using highly active antiretroviral therapy: case
      report.
AB  - CONTEXT: Highly active antiretroviral therapy (HAART) has turned human
      immunodeficiency virus (HIV) infection into a chronic condition, and this has led
      to increased incidence of anal dysplasia among HIV-positive patients. Routine
      anal evaluation including the anal canal and perianal area is recommended for
      this population, especially for patients infected by oncogenic human
      papillomavirus (HPV) types. CASE REPORT: A 54-year-old homosexual HIV-positive
      man presented with a six-year history of recurrent perianal and anal warts. He
      had previously undergone incomplete surgical excision and fulguration in another
      institution on two occasions. He had been using HAART over the past two years. He
      presented some condylomatous spreading lesions occupying part of the anal canal
      and the perianal skin, and also a well-demarcated slightly painful perianal
      plaque of dimensions 1.0 x 1.0 cm. Both anal canal Pap smears and biopsies guided
      by high-resolution anoscopy revealed high-grade squamous intraepithelial lesion.
      Biopsies of the border of the perianal plaque also revealed high-grade squamous
      intraepithelial lesion. HPV DNA testing of the anus detected the presence of HPV
      16 type. The patient underwent local full-thickness excision of the lesion.
      Histological analysis on the excised tissue revealed high-grade squamous
      intraepithelial lesion with one focus of microinvasive squamous cell cancer
      measuring 1 mm. No lymph vessel or perineural invasion was detected. The patient
      showed pathological evidence of recurrent anal and perianal high-grade squamous
      intraepithelial lesions at the sixth-month follow-up and required further
      ablation of those lesions. However no invasive squamous cell carcinoma recurrence
      has been detected so far.

PMID- 18094899
TI  - Laryngeal adenoid cystic carcinoma: case report.
AB  - CONTEXT: Adenoid cystic carcinomas are malignant tumors that occur in both the
      major and the minor salivary glands. A laryngeal location is rare because of the
      paucity of accessory salivary glands in this area. Adenoid cystic carcinomas
      account for less than 1% of all malignant tumors in the larynx, and only about
      120 cases have been reported in the literature. These tumors have a slight female
      predisposition, and their peak incidence is in the fifth and sixth decades of
      life. In this article, we describe a case of laryngeal adenoid cystic carcinoma
      and discuss its clinical characteristics and treatment. CASE REPORT: We report on
      a case of laryngeal adenoid cystic carcinoma in a 55 year-old female patient who
      presented with dyspnea and hoarseness. Features of the diagnostic and therapeutic
      evaluation are described and the clinical management of such cases is outlined.
      The clinical course, definitive treatment strategy and surgical procedure, and
      also adjuvant treatment with irradiation are discussed. Although the tumor is
      radiosensitive, it is not radiocurable.

PMID- 18094900
TI  - Primary mucinous adenocarcinoma of the bladder with signet-ring cells: case
      report.
AB  - CONTEXT: Primary adenocarcinomas of the bladder are uncommon and usually occur by
      contiguity with or hematogenic dissemination of other adenocarcinomas such as
      colorectal, prostate and gynecological tract carcinomas. Mucinous and signet-ring
      cell histological patterns are even rarer and it is often difficult to
      morphologically distinguish them from metastatic colorectal adenocarcinoma. CASE
      REPORT: We present and discuss a rare case of primary mucinous adenocarcinoma of
      the bladder with signet-ring cells in a 57-year-old male patient. Other primary
      sites for the tumor had been excluded and, in the absence of digestive tract
      tumor and for confirmation that it was a primary bladder tumor, an
      immunohistochemistry study was performed.

PMID- 18094901
TI  - Clinical and epidemiological characteristics of Helicobacter pylori infection
      among patients in specialty outpatient clinics at Faculdade de Medicina ABC.

PMID- 18094902
TI  - By the way, doctor: we've heard that sudden unexpected death in epilepsy is not a
      rare event. Do you know anything about this?

PMID- 18094904
TI  - [Positional plagiocephaly. Diagnosis and treatment].
AB  - INTRODUCTION: Positional plagiocephaly is nowadays the most frequent consultation
      at pediatric neurosurgical departments in Spain and western countries. Another
      important issue is the confusion existing in literature regarding terminology,
      physiopathology, differential diagnosis with true synostosis and, of course,
      proper recommendations for treatment. OBJECTIVES: To clarify all these concepts
      and present a protocol that was recently asked by the Health Administration of
      the Community of Madrid. PROTOCOL: Pretends to achieve coordination among
      paediatricians and neurosurgeons, as much as to offer precise information about
      data concerning this entity for parents, paediatricians and neurosurgeons.
      MATERIAL AND METHODS: Previous consensus is reached about some data. Children are
      classified in three categories of deformation (mild; moderate; severe), according
      to measurements on digital photography. Diagnosis and treatment follows two
      phases: Paediatric phase (up to 5 months of age) and Neurosurgical phase (from 5
      months on). Children would be referred to neurosurgical consultation only after
      being treated with postural changes and physiotherapy by the age of 5 months.
      Reasons are explained in the protocol that defines also functions and
      responsibilities for each speciality. CONCLUSION: Treatment proposed here is
      staged, starting with postural changes and physiotherapy, followed by orthotic
      cranial devices and finally surgical treatment.

PMID- 18094905
TI  - [Lumbar post-laminectomy syndrome I. Pain management using interventionist
      techniques].
AB  - Chronic low back pain and ciatica after surgery is one of the main reasons for
      referring patients to multidisciplinary pain units (MPU). The future expansions
      of MPU have promted neurosurgeons in Spain to re-enter the field of chronic pain
      management and to recover their enthusiam, that have been lost severel years ago
      for various reasons. We do not intend dealing with the new instrumented surgical
      options for the post-laminectoy pain, but rather into the indications and
      descriptions of the interventional techniques for lumbar and sciatic pain
      managemet. Currently there are a great number of percutaneous techniques to
      achieve pain control in the post-laminectomy syndrome. Traditional neuroablative
      techniques at the spinal cord or the cerebral levels are not any longer
      indicated. Nonetheless, lumbar sympathectomy and thermo-neurolisis either with
      chilling or heating, are back in favour, due to the development of new devices
      and applications. Neuromodulation techniques which are also applicable to this
      pathology will be the subjet of another article. Pulsed radio-frecuency apperars
      to favour the safe application of electricity to the dorsal root ganglion or to
      the root itself thus avoiding the fear of permanent root and/or ganglion thermal
      lesions that frecuently occurred with the older techniques. Several strategies
      for pain relief are described, step by step and real figures are depicted in
      order to make the procedures more understandable and for the easier transmission
      of knowledge.

PMID- 18094906
TI  - [Computerized atlas for image-guided stereotactic functional neurosurgery].
AB  - OBJECTIVE: A computerized version of the Schaltenbrand and Wahren's stereotactic
      brain atlas for image-guided functional neurosurgery planning has been developed
      and integrated into our PC-based planning system. METHODS: The SW atlas plates
      were digitized, contoured and labeled for both hemispheres. The computerized
      atlas may be interactively registered with patient's data using linear and non
      linear transformation. The implemented computational tools and applications are
      presented. RESULTS: Our computer system permits navigation through original or
      reconstructed slices, multiple-views synchronization and zoom to improve the
      localization of the commisures and the surgical targets, likewise the optimum
      path selection. Atlas position in the target's region can be interactively
      actualized and lesion's position and volume may be simulated. CONCLUSIONS: Its
      benefits of this approach include increased accuracy of target definition,
      decreased the number of electrode tracts and for instance the time of the
      surgery, and reduced surgical complications.

PMID- 18094907
TI  - [Complications of the direct endonasal transsphenoidal approach in the management
      of pituitary adenomas].
AB  - OBJECTIVE: To describe the frequency of complications and complaints caused by
      direct endonasal transsphenoidal approach used in the resection of pituitary
      adenomas. PATIENTS AND METHODS: In a retrospective way, we review patients'
      records with pituitary adenomas, operated by means of direct endonasal
      transsphenoidal approach, between August 2003 and December 2004. We recollected
      information about operative and postoperative complications, besides complaints
      registered in patients' records. RESULTS: 41 patients were included, 23 (56.1%)
      males and 18 (43.9%) females, with a mean age of 47.7 -/+16.8 years. Operative
      complications were intrasellar hemorrhage in three patients (7.3%), hypertension
      in two (4.9%) and cerebrospinal fluid fistula in one (2.4%). On the other hand,
      postoperative complications were diabetes insipidus (24.4%) in ten cases,
      anterior pituitary insufficiency (4.9%) in two and sinusitis (2.4%) in one. Nasal
      congestion was the most common complaint (31.7%) in thirteen patients.
      CONCLUSIONS: Supported in our results, the direct endonasal transsphenoidal
      approach tends to present mainly fewer nasal complications and complaints, and in
      the future it could be considered like the preferred approach for resection of
      pituitary adenomas.

PMID- 18094908
TI  - [Neuroanesthetic practice in Catalonia. Results of a survey done on 2003].
AB  - INTRODUCTION: Health system planning requires the precise knowledge of the
      activity performed. We present the neuroanesthesic activity results in Catalonia
      during 2003. METHODS: A prospective and cross-sectional survey was performed for
      14 randomised days during 2003. All hospitals practicing anaesthesia in Catalonia
      took part in the survey. Data on characteristics of patients, anaesthetic
      techniques and type of procedure were included. RESULTS: 6909 neuroanesthetic
      procedures performed in Catalonia in 2003 (95% IC 6022-7847), a 1.28% of total
      surgical activity. A 74% of procedures were done in the public hospitals and a
      26% in private hospitals. Patients mean age was 48 years old (95% IC 45.5-50.6).
      Scheduled procedures were 79.7%. The most frequent interventions were: Spine
      surgery 40.1 %; craniotomies for tumour resection 24.1%, for haemorrhage o trauma
      7.2% and for aneurysms or AVM surgery 2.3%; ventricular shunts 2.6%. Mean
      duration of craneotomies for tumour resection was 287 -/+95 min. All patients
      were distributed postoperatively in a conventional recovery room (55.8 %), in a
      monitored care unit (19.2%) or in an intensive care unit (24.9 %). Craniotomy
      patients were admitted to an intensive care unit (41.6%), a monitored care unit
      (33.7%) or a conventional recovery room (24.7%). CONCLUSIONS: About seven
      thousand Neurosurgical procedures were performed in Catalonia in 2003, in public
      (73.6%) and private (26.4%) hospitals. Spine surgery and craniotomies for tumour
      resection were the most frequently performed interventions. Craniotomy patients
      were mainly submitted to an ICU or a Monitored care unit.

PMID- 18094909
TI  - [Solitary fibrous tumors of the meninges: report of three cases and literature
      review].
AB  - We report 3 patients with fibrous solitary tumor of meningeal location where we
      described the histological study, as well as evolution after the surgical
      treatment. The described patients presented ages of 37, 52 and 65 years, after
      the resection has not appeared an objective sign of recurrence in any case after
      4, 6 and 7 years of follow-up respectively. Checking the literature the tumor is
      indistinguishable clinical and radiolocally of the typical meningioma, doing
      necessary the use of inmunohistochemistry to do the differential diagnosis, where
      positiveness for CD34 and the negativeness for EMA define the fibrous solitary
      tumor. It is about a benign tumor, where total removing is the principal factor
      in prognosis, nevertheless there are cases of local recurrences and long-distance
      metastasis. We can find all these characteristics in the showed cases of the
      present article, having the uncertainty of its local or systemic relapse ability
      in the future.

PMID- 18094910
TI  - Cervical lipomyelomeningocele: case illustration.
AB  - Cervical lipomyelomeningocele is a rare congenital spinal pathology.
      Lipomyelomeningocele is the commonest cause of congenital tethering, which causes
      neurological deterioration due to the conus medullaris and root ischemia. Early
      intervention is recommended even in cases with normal neurological examinations
      in order to prevent deterioration but our patient with cervical
      lipomyelomeningocele had a normal neurological examination despite his age (22
      year-old) and had no urodynamic dysfunction.

PMID- 18094911
TI  - Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in
      beagle dog vertebra.
AB  - Changes in organic matrix may contribute to the anti-fracture efficacy of anti
      remodeling agents. Following one year of treatment in beagle dogs,
      bisphosphonates alter the organic matrix of vertebral trabecular bone, while
      raloxifene had no effect. These results show that pharmacological suppression of
      turnover alters the organic matrix component of bone. INTRODUCTION: The collagen
      matrix contributes significantly to a bone's fracture resistance yet the effects
      of anti-remodeling agents on collagen properties are unclear. The goal of this
      study was to assess changes in collagen cross-linking and isomerization following
      anti-remodeling treatment. METHODS: Skeletally mature female beagles were treated
      for one year with oral doses of vehicle (VEH), risedronate (RIS; 3 doses),
      alendronate (ALN; 3 doses), or raloxifene (RAL; 2 doses). The middle dose of RIS
      and ALN and the lower dose of RAL approximate doses used for treatment of post
      menopausal osteoporosis. Vertebral trabecular bone matrix was assessed for
      collagen isomerization (ratio of alpha/beta C-telopeptide [CTX]), enzymatic
      (pyridinoline [PYD] and deoxypyridinoline [DPD]), and non-enzymatic (pentosidine
      [PEN]) cross-links. RESULTS: All doses of both RIS and ALN increased PEN (+34
      58%) and the ratio of PYD/DPD (+14-26%), and decreased the ratio of alpha/beta
      CTX (-29-56%) compared to VEH. RAL did not alter any collagen parameters. Bone
      turnover rate was significantly correlated to PEN (R = -0.664), alpha/beta CTX (R
      = 0.586), and PYD/DPD (R = -0.470). CONCLUSIONS: Bisphosphonate treatment
      significantly alters properties of bone collagen suggesting a contribution of the
      organic matrix to the anti-fracture efficacy of this drug class.

PMID- 18094912
TI  - Aquatic risk assessment of herbicides in freshwater ecosystems of South Florida.
AB  - Widespread, high-volume use and subsequent off-site transport of herbicides,
      specifically photosystem II inhibitors (PSII), on agricultural and noncultivated
      lands in south Florida has resulted in frequent detections in freshwater systems.
      In light of the current restoration efforts as part of the Comprehensive
      Environmental Restoration Plan (CERP), increased water flows containing
      detectable herbicide levels into the Everglades ecosystem and adjacent areas may
      have adverse consequences to the unique plant communities present in the region.
      The potential impact of individual herbicides to aquatic plant and algae species
      was examined using a probabilistic risk assessment approach. Risk was
      characterized for nine PSII herbicides (four triazines: ametryn, atrazine,
      simazine, and prometryn; two triazinones: hexazinone and metribuzin; two
      substituted ureas: diuron and linuron; and a uracil: bromacil) and a pyridazinone
      herbicide (norflurazon) by comparing the overlap of the 90th percentile surface
      water concentration (exposure benchmark) from the exposure distributions to the
      10th percentile of effects (effects benchmark) determined from species
      sensitivity distributions of acute laboratory toxicity data. Overall, the risk of
      the individual herbicides was generally low. A Multiple Substance Potentially
      Affected Fraction (msPAF) risk approach also was utilized to examine the joint
      toxicity of the herbicide mixtures based on a concentration addition model. The
      risk associated with the herbicide mixture (mainly bromacil, diuron, and
      norflurazon) was determined to be high for Lee (site S79 on the Caloosahatchee
      River), Martin (site S80 on St. Lucie Canal), and St. Lucie (site S99 on C25
      emptying into Indian River Lagoon) counties in south Florida. This study
      highlights the need to consider joint action of chemical mixtures as part of an
      ecological risk assessment.

PMID- 18094913
TI  - Central retinal artery occlusion following transcatheter balloon aortic
      valvuloplasty in an adolescent with aortic valvular stenosis.
AB  - A 12-year-old girl with aortic valvular stenosis underwent transcatheter balloon
      aortic valvuloplasty (BAV) using a femoral artery approach. Anticoagulation with
      heparin during the procedure was used. The patient noted sudden onset of
      concentric constriction of the visual field in the right eye 40 min after BAV.
      Brain magnetic resonance imaging and cervical ultrasound revealed no abnormality.
      Funduscopic examination showed white swelling around the macular region,
      indicating ischemia, consistent with central retinal artery occlusion (CRAO).
      CRAO should be recognized as a rare and serious complication associated with BAV
      even among the pediatric population. This requires careful evaluation of
      anticoagulation during the left heart procedures.

PMID- 18094914
TI  - Transcatheter closure of patent ductus arteriosus among native high-altitude
      habitants.
AB  - Increased prevalence of patent ductus arteriosus (PDA) at high altitude (HA) is a
      known occurrence. Transcatheter treatment of patients with PDA living at a HA is
      assessed in this study. Thirteen consecutive patients (all habitants of La Paz,
      Bolivia) underwent transcatheter closure of PDA. The minimal diameter of PDA was
      5.8 (1.5-11) mm and the mean pulmonary artery pressure was 37 (7-80) mm Hg. In 12
      patients, the Amplatzer Duct Occluder (ADO) was used; in one child with PDA with
      a 1.5-mm diameter, a detachable coil was implanted. All procedures, except for
      one, were completed successfully. The ADO (diameter: 12/10 mm) implantation
      failed in one child with pulmonary hypertension because the device could not be
      properly secured in position in a 6-mm PDA. Subsequent surgery was performed
      without any complications. No residual shunt after 24 h was observed in any case
      after treatment. No complications were encountered during the procedure and
      follow-up of 1.5 (from 0.1 to 2.8) years. PDA in native residents of high land
      have different physiopathologies and anatomies. ADO appears to be a suitable
      device for transcatheter occlusion for most such patients. Interventional
      cardiology in countries with residents at high altitudes can be helpful in
      addressing this issue.

PMID- 18094915
TI  - Successful use of covered stent to treat superior systemic baffle obstruction and
      leak after atrial switch procedure.
AB  - Progressive dyspnea and cyanosis occurred in a 41-year-old patient status after
      Mustard atrial switch repair for transposition of great arteries. Cardiac
      catheterization and magnetic resonance imaging revealed the association of
      superior limb systemic venous baffle obstruction and leaks with right-to-left
      shunting. He underwent successful dilation of the venous channel and obstruction
      of baffle leaks by using a covered stent.

PMID- 18094916
TI  - Cholesterol screening in an at-risk pediatric population.
AB  - Elevation of low-density lipoprotein (LDL) cholesterol is a recognized risk
      factor for premature atherosclerosis and such elevations have their antecedents
      in the pediatric population. This study evaluated the frequency of elevated LDL
      cholesterol in children and adolescents (8-18 years) in whom one parent had a
      history of premature ischemic heart disease (<55 years). Patients had a fasting
      lipid profile performed and results were classified as normal, borderline/high,
      or high in accordance with the American Academy of Pediatrics (AAP) guidelines.
      Fifty-two parents had a total of 97 children and adolescents who were eligible
      for screening. Ninety-three initially consented and fasting lipid profiles were
      obtained in 82 (84.5%) children. Prevalences of high and borderline/high LDL
      cholesterol were (7/82) 8.5% and (17/82) 20.7%, respectively. Screening for
      hypercholesterolemia in these at-risk children and adolescents is prudent and
      dietary advice must be offered.

PMID- 18094917
TI  - Multiple courses of indomethacin and neonatal outcomes in premature infants.
AB  - The objective of this retrospective cohort study was to determine patent ductus
      arteriosus (PDA) closure rate with multiple short courses (three doses) of
      postnatal indomethacin and compare neonatal outcomes in infants who received two
      versus three courses of indomethacin for PDA closure. Infants <34 weeks'
      gestational age born between January 2000 and December 2004 at the University of
      Maryland Medical Center and who received two or more short courses of
      indomethacin were included. Outcome measures were ductal closure rate and
      neonatal outcomes. Of 61 infants who were identified to have received two or more
      courses of indomethacin, 26 infants closed their ductus after the second course
      (response rate, 42%). Of the 35 infants who failed ductal closure after two
      courses, 11 infants had their ductus ligated and 23 received a third course of
      indomethacin. Of 23 who received a third course, 10 closed their ductus (response
      rate, 43%). There was no significant difference in the incidence of chronic lung
      disease, severe retinopathy of prematurity, necrotizing enterocolitis, renal
      function, or mortality between infants who received two and those who received
      three courses of indomethacin. Infants exposed to three courses of indomethacin
      had a statistically nonsignificant increased incidence of periventricular
      leukomalacia (p = 0.08; adjusted odds ratio = 4.8; 95% CI, 0.8-30) and remained
      in the hospital for a longer duration (p = 0.02) compared to infants exposed to
      two courses of indomethacin. We conclude that multiple courses of indomethacin
      may be associated with a ductal closure. However, the requirement for a third
      course may be associated with an increased risk of periventricular leukomalacia.

PMID- 18094918
TI  - Old and rare books concerning human anatomic variations available at the Medical
      University of Sofia, Bulgaria.

PMID- 18094919
TI  - The velum interpositum revisited and redefined.
AB  - INTRODUCTION: Descriptions of the velum interpositum (VI) are typically brief and
      lacking detail in most neuroanatomical and neurosurgical texts. As this structure
      may be involved clinically or encountered surgically, the present study seemed
      warranted. MATERIALS AND METHODS: Twenty-adult (10 male and 10 female) formalin
      fixed and fresh cadaveric brains underwent a detailed dissection of the VI via an
      interhemispheric transcollosal approach. Observations were made of the attachment
      sites and continuation of the VI. Measurements were made of its length and width
      at its anterior, midportion, and posterior parts. RESULTS: The VI extended
      laterally over the thalami to become continuous with the choroid plexus of the
      lateral ventricles. At a point along the thalami where the choroid plexus was
      found, the VI became "tacked" down and thus continuous with the choroid plexus
      subependymally. No specimen exhibited a separate choroid plexus of the third
      ventricle. In each, the choroid plexus of the lateral and third ventricles were
      the same tissue layer, all arising from the VI. This structure was adherent to
      but not fused to the deep surface of the fornix. The VI was also not fused to the
      pineal gland or habenula commissure but simply covered these structures. This
      membrane was confluent with the pia/arachnoid over the cerebellum and from the
      inferior surface of the parietal/occipital lobes and extended laterally into the
      choroid fissure. CONCLUSIONS: To our knowledge, the extent of the VI as described
      herein has not been reported earlier. The supratentorial choroid plexus is simply
      a vascular extension of the VI. There is no separate choroid plexus of the third
      ventricle as often described. Clear planes exist between the VI and surrounding
      structures such as the pineal gland. Such data may be useful to neurosurgeons who
      operate in this region and to clinicians who interpret imaging in the area of the
      VI.

PMID- 18094920
TI  - Diagnostic value and surgical implications of the magnetic resonance imaging in
      the management of adult patients with brachial plexus pathologies.
AB  - The imaging of the brachial plexus (BP) cannot easily be achieved because of the
      extension of the region to be studied, the different tissue compositions of the
      adjacent anatomic structures and the necessity to work with thin tissue slices.
      Here is a description of the brachial plexus MRI (bpMRI) protocol that we use for
      the pre-operative evaluation of patients affected by the following brachial
      plexus (BP) pathologies: neoplastic, post-traumatic, inflammatory. The surgical
      implications are discussed. A survey was done on 115 patients (66 males; 49
      females; mean age 46.4 years old), which underwent a bpMRI over a 32-month period
      (32 post-traumatic, 26 neoplastic, 25 affected by inflammatory diseases). Our
      bpMRI protocol is evaluated according to each mechanism of disease. The bpMRI
      provides a topographic localization of the tumour showing the nerve dislocations
      or infiltration by the neoplasm. In traumatic patients we suggest that the bpMRI
      could be useful to detect the degree of axonal damage when the nerve lesion is in
      continuity. We also consider the diagnosis and the possible surgical implications
      for the inflammatory plexopathies. In conclusion, a standardized bpMRI protocol
      has an invaluable diagnostic value for the surgeons and neurologists. It is only
      limited by its duration (at least 45 min).

PMID- 18094922
TI  - Functional rescue of an oligomerization-defective HIV-1 Rev mutant by fusion with
      an oligomeric tag.
AB  - The HIV-1 wild-type Rev and the negative oligomerization-defective mutant RevM4
      were fused to enhanced green fluorescent protein (EGFP) and the tetrameric red
      fluorescent protein (DsRed1) followed by examination of their intracellular
      localization and Rev activity. As previously shown, fusion of EGFP to Rev and
      RevM4 did not affect the biological activity. Fusion of DsRed1 to Rev inhibited
      activity, and interestingly, fusion of DsRed1 to RevM4 restored activity. Based
      on these results, a model is proposed suggesting how RevM4-DsRed1 is able to
      rescue Rev activity through oligomerization on the viral RNA.

PMID- 18094921
TI  - Activation of NF-kappaB p65/c-Rel dimer is associated with neuroprotection
      elicited by mGlu5 receptor agonists against MPP(+) toxicity in SK-N-SH cells.
AB  - Nuclear factor-kappaB (NF-kappaB) is a transcriptional regulator of neuron
      survival eliciting diverse effects according to the specific composition of its
      active dimer. While p50/p65 mediates neurodegenerative events, c-Rel-containing
      dimers promote cell survival. Stimulation of metabotropic glutamate receptors
      type 5 (mGlu5) reduces neuron vulnerability to amyloid-beta through activation of
      anti-apoptotic, c-Rel-dependent transcription of Bcl-X(L) pathway. We here
      evaluated the protective activity of mGlu5 agonists in dopaminergic SK-N-SH cells
      exposed to 1-methyl-4-phenylpyridinium (MPP(+)), the active metabolite of 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causing parkinsonism in
      experimental animals. MPP(+) produced a concentration-dependent cell loss.
      Activation of mGlu5 receptors by CHPG (1 mM) and 3HPG (50 microM) abolished the
      toxic effect produced by 3 microM MPP(+). The neuroprotection was associated with
      activation of NF-kappaB p65/c-Rel dimer and reduction of p50/p65. These effects
      were prevented by the mGlu5 receptor antagonist MPEP (5 microM). It is suggested
      that mGlu5 receptor agonists through activation of a c-Rel-dependent anti
      apoptotic pathway can rescue dopaminergic cell from mitochondrial toxicity.

PMID- 18094923
TI  - Complete nucleotide sequence of an isolate of coleus vein necrosis virus from
      verbena.

PMID- 18094924
TI  - An integrated physiological and genetic approach to the dynamics of FtsZ
      targeting and organisation in a moss, Physcomitrella patens.
AB  - Plant FtsZ (filamentous temperature-sensitive Z) proteins are regarded as
      descendants of prokaryotic cell division proteins. We could show previously that
      four FtsZ isoforms of the moss Physcomitrella patens assemble into, and interact
      in, distinct structures inside the chloroplasts and in the cytosol. Their
      organisation and localisation patterns indicate an involvement in chloroplast and
      cell division and in the maintenance of chloroplast shape and integrity. The
      cellular processes of chloroplast division and maintenance of chloroplast shape
      were disturbed either by application of the beta-lactam antibiotic ampicillin or
      by a mutation that presumably affects signal transduction of the plant hormone
      cytokinin. When cells of these plants were analysed microscopically, there was no
      indication that cytosolic functions of FtsZ proteins were affected. Furthermore,
      FtsZ proteins continued to build three-dimensional plastoskeleton networks, even
      in considerably enlarged or malformed chloroplasts. On the other hand,
      macrochloroplast formation promoted the localisation of FtsZ proteins in
      filaments that emanate from the plastids and, therefore, most likely represent
      stromules. Annular FtsZ structures that are regarded as essential components of
      the division apparatus were absent from macrochloroplasts of ampicillin-treated
      cells. Thus, the distribution of FtsZ proteins after inhibition of chloroplast
      division further strengthens our hypothesis on the functions of distinct
      isoforms. In addition, the results provide further insight into the regulation of
      protein targeting and dynamics of plastoskeletal elements.

PMID- 18094925
TI  - Intracellular localization of integrin-like protein and its roles in osmotic
      stress-induced abscisic acid biosynthesis in Zea mays.
AB  - Plants have evolved many mechanisms to cope with adverse environmental stresses.
      Abscisic acid (ABA) accumulates significantly in plant cells in response to
      drought conditions, and this is believed to be a major mechanism through which
      plants enhance drought tolerance. In this study, we explore the possible
      mechanisms of osmotic stress perception by plant cells and the consequent
      induction of ABA biosynthesis. Immunoblotting and immunofluorescence localization
      experiments, using a polyclonal antibody against human integrin beta1, revealed
      the presence of a protein in Zea mays roots that is similar to the integrin
      proteins of animals and mainly localized in the plasma membrane. Treatment with
      GRGDS, a synthetic pentapeptide containing an RGD domain, which interacted
      specifically with the integrin protein and thus blocked the cell wall-plasma
      membrane interaction, significantly inhibited osmotic stress-induced ABA
      biosynthesis in cells, and the GRGDS analog which does not contain the RGD domain
      had no effect. Our results show that a strong interaction exists between the cell
      wall and plasma membrane and that this interaction is largely mediated by
      integrin-like proteins. They also imply that the cell wall and/or cell wall
      plasma membrane interaction plays important roles in the perception of osmotic
      stress. Accordingly, we conclude that the cell wall and/or cell wall-plasma
      membrane interaction mediated by the integrin-like protein plays important roles
      in osmotic stress-induced ABA biosynthesis in Zea mays.

PMID- 18094926
TI  - Aspects of programmed cell death during early senescence of barley leaves:
      possible role of nitric oxide.
AB  - Leaf senescence is a highly coordinated process which involves programmed cell
      death (PCD). Early stages of leaf senescence occurring during normal leaf
      ontogenesis, but not triggered by stress factors, are less well known. In this
      study, we correlated condensation of chromatin and nuclear DNA (nDNA)
      fragmentation, two main features of PCD during early senescence in barley leaves,
      with the appearance of nitric oxide (NO) within leaf tissue. With the help of the
      alkaline version of the comet assay, together with measurements of nDNA
      fluorescence intensity, we performed a detailed analysis of the degree of nDNA
      fragmentation. We localised NO in vivo and in situ within the leaf and
      photometrically measured its concentration with the NO-specific fluorochrome 4
      amino-5-methylamino-2',7'-difluorofluorescein. We found that both nDNA
      fragmentation and chromatin condensation occurred quite early during barley leaf
      senescence and always in the same order: first nDNA fragmentation, in leaves of 6
      day-old seedlings, and later chromatin condensation, in the apical part of leaves
      from 10-day-old seedlings. PCD did not start simultaneously even in neighbouring
      cells and probably did not proceed at the same rate. NO was localised in vivo and
      in situ within the cytoplasm, mainly in mitochondria, in leaves at the same stage
      as those in which chromatin condensation was observed. Localisation of NO in
      vascular tissue and in a large number of mesophyll cells during the senescence
      process might imply its transport to other parts of the leaf and its involvement
      in signalling between cells. The fact that the highest concentration of NO was
      found in the cytoplasm of mesophyll cells in the earliest stage of senescence and
      lower concentrations were found during later stages might suggest that NO plays
      an inductive role in PCD.

PMID- 18094927
TI  - Additional nucleoli and NOR activity during meiotic prophase I in larch (Larix
      decidua Mill.).
AB  - Transcriptional activity was investigated in successive stages of prophase I
      (male meiosis) of larch meiocytes. Br-UTP incorporated into RNA was detected by
      light and electron microscopy. Two peaks of RNA synthesis were identified in the
      nucleolus. The first occurred during the zygotene-pachytene stage and the second
      (not previously described in plant meiocytes) in the diplotene. These processes
      correlated with a considerable increase in nucleolus volume during these periods.
      At the end of the zygotene, several perinucleolar structures lying close to each
      other and containing rRNA, argyrophilic proteins, U3 small nucleolar RNA, and
      fibrillarin were observed. The occurrence of newly formed RNA was also observed
      in these structures. This suggests that the observed perinucleolar structures
      correspond to the additional nucleoli known from animals.

PMID- 18094928
TI  - Pyrus pyrifolia stylar S-RNase induces alterations in the actin cytoskeleton in
      self-pollen and tubes in vitro.
AB  - Pears (Pyrus pyrifolia L.) have an S-RNase-based gametophytic self
      incompatibility system, and S-RNases have also been implicated in self-pollen or
      genetically identical pollen rejection. Tip growth of the pollen tube is
      dependent on a functioning actin cytoskeleton. In this study, configurations of
      the actin cytoskeleton in P. pyrifolia pollen and effects of stylar S-RNases on
      its dynamics were investigated by fluorescence and confocal microscopy. Results
      show that actin filaments in normal pollen grains exist in fusiform or circular
      structures. When the pollen germinates, actin filaments assembled around one of
      the germination pores, and then actin bundles oriented axially throughout the
      shank of the growing tube. There was a lack of actin filaments 5-15 microm from
      the tube tip. When self-stylar S-RNase was added to the basal medium, pollen
      germination and tube growth were inhibited. The configuration of the actin
      cytoskeleton changed throughout the culturing time: during the first 20 min, the
      actin configurations in the self-pollen and tube were similar to the control;
      after 20 min of treatment, the actin filaments in the pollen tube gradually moved
      into a network running from the shank to the tip; finally, there was punctate
      actin present throughout the whole tube. Although the actin filaments of the self
      pollen grain also disintegrated into punctate foci, the change was slower than in
      the tube. Furthermore, the alterations to the actin cytoskeleton occurred prior
      to the arrest of pollen tube growth. These results suggest that P. pyrifolia
      stylar S-RNase induces alterations in the actin cytoskeleton in self-pollen
      grains and tubes.

PMID- 18094929
TI  - Heterologous expression of vacuolar H(+)-PPase enhances the electrochemical
      gradient across the vacuolar membrane and improves tobacco cell salt tolerance.
AB  - The vacuolar H(+)-translocating inorganic pyrophosphatase (H(+)-PPase) uses
      pyrophosphate as substrate to generate the proton electrochemical gradient across
      the vacuolar membrane to acidify vacuoles in plant cells. The heterologous
      expression of H(+)-PPase genes (TsVP from Thellungiella halophila and AVP1 from
      Arabidopsis thaliana) improved the salt tolerance of tobacco plants. Under salt
      stress, the transgenic seedlings showed much better growth and greater fresh
      weight than wild-type plants, and their protoplasts had a normal appearance and
      greater vigor. The cytoplasmic and vacuolar pH in transgenic and wild-type cells
      were measured with a pH-sensitive fluorescence indicator. The results showed that
      heterologous expression of H(+)-PPase produced an enhanced proton electrochemical
      gradient across the vacuolar membrane, which accelerated the sequestration of
      sodium ions into the vacuole. More Na(+) accumulated in the vacuoles of
      transgenic cells under salt (NaCl) stress, revealed by staining with the
      fluorescent indicator Sodium Green. It was concluded that the tonoplast-resident
      H(+)-PPase plays important roles in the maintenance of the proton gradient across
      the vacuolar membrane and the compartmentation of Na(+) within vacuoles, and
      heterologous expression of this protein enhanced the electrochemical gradient
      across the vacuolar membrane, thereby improving the salt tolerance of tobacco
      cells.

PMID- 18094930
TI  - Actin and myosin inhibitors block elongation of kinetochore fibre stubs in
      metaphase crane-fly spermatocytes.
AB  - We used an ultraviolet microbeam to cut individual kinetochore spindle fibres in
      metaphase crane-fly spermatocytes. We then followed the growth of the
      "kinetochore stubs", the remnants of kinetochore fibres that remain attached to
      kinetochores. Kinetochore stubs elongate with constant velocity by adding tubulin
      subunits at the kinetochore, and thus elongation is related to tubulin flux in
      the kinetochore microtubules. Stub elongation was blocked by cytochalasin D and
      latrunculin A, actin inhibitors, and by butanedione monoxime, a myosin inhibitor.
      We conclude that actin and myosin are involved in generating elongation and thus
      in producing tubulin flux in kinetochore microtubules. We suggest that actin and
      myosin act in concert with a spindle matrix to propel kinetochore fibres
      poleward, thereby causing stub elongation and generating anaphase chromosome
      movement in nonirradiated cells.

PMID- 18094931
TI  - Mitochondrial sequestration of BCECF after ester loading in the giant alga Chara
      australis.
AB  - Ratiometric fluorescent dyes are often used to monitor free ion concentrations in
      vivo, especially in cells that are recalcitrant to transformation with
      genetically encoded fluorescent markers. Although intracellular dye distributions
      are often found to be cytosolic, dye localisation has often not been examined in
      detail. We began exploring the use of BCECF (2',7'-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein) to monitor pH in the giant alga Chara australis and
      discovered that younger leaf cells could be loaded using the acetoxymethyl ester
      of BCECF. However, we were puzzled to find in microphotometric measurements that
      the fluorescence ratio appeared insensitive to manipulations affecting cytosolic
      pH. Confocal imaging of C. australis cells loaded with BCECF showed an
      accumulation of the dye in two locations: (1) on the outside of the chloroplasts
      in irregularly shaped stationary bodies; (2) within 1-1.5 mum structures that
      moved rapidly with the pericellular cytoplasmic streaming. Together with the
      streaming cytoplasm, these organelles were rendered stationary with 50 muM
      cytochalasin D. Rhodamine 123, a mitochondrionspecific dye, highlighted
      organelles outside of the chloroplasts, similar to those shown by BCECF in
      location 1. We conclude that in the cytoplasmic compartment, BCECF was
      sequestered within cytoplasmic mitochondria in immature and fast-growing cells
      and within the cortical mitochondrial system in older and slowly growing cells.
      Thus, BCECF-AM is unsuitable for reporting changes in cytosolic pH in C.
      australis but might be employed in future to study pH changes in the
      mitochondria.

PMID- 18094932
TI  - No changes in infliximab levels in blood stored for preoperative autologous blood
      donation.
AB  - Rheumatoid arthritis (RA) patients requiring total joint arthroplasties under
      administration of infliximab, which may remain in donated blood if preoperative
      autologous blood donation (PABD) is undertaken for the surgery, may risk
      infection. We clarified infliximab hemokinetics in blood stored for such
      patients. A 20-ml blood sample was obtained from each of the ten RA patients
      receiving infliximab at just after administration and at 2 and 4 weeks following
      the administration of infliximab, mixed with 2.8 ml citrate-phosphate-dextrose
      adenine (CPDA-1) and stored at 4-6 degrees C. Plasma levels of infliximab in the
      stored blood were measured just after-mixture with CPDA-1, and at 2 and 4 weeks
      following the start of storage. Serum levels were also measured just before
      infliximab administration and at each phlebotomy. The plasma infliximab levels in
      the stored blood remained close to their original serum levels at the time of
      each corresponding phlebotomy, only somewhat influenced by dilution of CPDA-1,
      and sustained for 4 weeks following the start of storage, unlike in vivo, where
      levels decreased. This suggests that in order to prevent side effects, the later
      after infusion of infliximab the phlebotomy occurs, the better, and that the
      amount of stored blood transfusion should be consistent with that of blood loss.

PMID- 18094933
TI  - Peripheral CD4+ T cells showing a Th2 phenotype in a patient with Mikulicz's
      disease associated with lymphadenopathy and pleural effusion.
AB  - Mikulicz's disease (MD) is a unique IgG4-related systemic disease indicated by
      enlargement of the lachrymal and salivary glands and which differs substantially
      from Sjogren's syndrome. A male patient with pleural effusion, swelling of the
      submandibular glands, and swelling of the paraaortic, mediastinal, and pararenal
      lymph nodes was diagnosed with MD. Analysis of peripheral CD4+ T cells from the
      patient revealed deviation of the Th1/Th2 balance to Th2. Prednisolone therapy
      ameliorated the disease and corrected the Th1/Th2 imbalance.

PMID- 18094934
TI  - Can deformation of a polymer film with a rigid coating model geophysical
      processes?
AB  - The structural and mechanical behavior of polymer films with a thin rigid coating
      is analyzed. The behavior of such systems under applied stress is accompanied by
      the formation of a regular wavy surface relief and by regular fragmentation of
      the coating. The above phenomena are shown to be universal. Both phenomena
      (stress-induced development of a regular wavy surface relief and regular
      fragmentation of the coating) are provided by the specific features of mechanical
      stress transfer from a compliant soft support to a rigid thin coating. The above
      phenomena are associated with a specific structure of the system, which is
      referred to as "a rigid coating on a soft substratum" system (RCSS). Surface
      microrelief in RCSS systems is similar to the ocean floor relief in the vicinity
      of mid-oceanic ridges. Thus, the complex system composed of a young oceanic crust
      and upper Earth's mantle may be considered as typically "a solid coating on a
      soft substratum" system. Specific features of the ocean floor relief are analyzed
      in terms of the approach advanced for the description of the structural
      mechanical behavior of polymer films with a rigid coating. This analysis allowed
      to estimate the strength of an ocean floor.

PMID- 18094935
TI  - Phase I study of a novel pro-apoptotic drug R-etodolac in patients with B-cell
      chronic lymphocytic leukemia.
AB  - R-etodolac is a novel pro-apoptotic agent with potential antitumor activity
      against B-cell chronic lymphocytic leukemia (B-CLL). This phase I clinical trial
      was conducted to determine the tolerability, safety, and maximum tolerated dose
      (MTD) of R-etodolac, administered orally twice a day (BID), in patients with B
      CLL. Secondary objectives included evaluating clinical response, pharmacodynamic
      activity (reduction of lymphocytes), and pharmacokinetic (PK) profile. Forty
      three patients were enrolled in the study. The most frequently reported adverse
      events were diarrhea, rash, pruritus, and headache. Increases in alanine
      aminotransferase (ALT) were also observed. Adverse events were generally mild and
      self-limiting, although in an apparent dose-response relationship, grade 2 and 3
      gastrointestinal toxicities and grade 3 skin toxicities were reported with the
      highest dose regimens (1,800 and 2,400 mg BID). Hematologic toxicity was rare.
      The MTD was determined to be 1,200 mg BID. PK results indicated that oral
      absorption of R-etodolac was rapid (time to maximum concentration ranged from 2
      to 4 h), and the half-life ranged from 5 to 7 h. The increase in maximum
      concentration, however, was not proportional to the increase in dose. R-etodolac
      significantly reduced absolute lymphocyte count (ALC) in B-CLL patients in a dose
      dependent manner up to 1,800 mg BID and caused partial responses in 2 patients.
      Further study of R-etodolac as a possible new maintenance therapy or as a part of
      combination therapy of B-CLL appears warranted.

PMID- 18094937
TI  - A surprising cause of sinusitis.

PMID- 18094936
TI  - Safety and efficacy of the direct endonasal transsphenoidal approach for
      challenging sellar tumors.
AB  - INTRODUCTION: The direct endonasal approach to pituitary microadenomas is
      relatively atraumatic, rapid, and carries a lower complication rate than the
      sublabial approach. Large macroadenomas (3-4 cm) can still be addressed with this
      simple, unmodified direct endonasal approach. We present our experience with this
      unique and challenging patient population. METHODS: About 64 consecutive patients
      with large (3-4 cm) pituitary adenomas and craniopharyngiomas were treated by the
      senior author (SK) using the direct endonasal approach from May 2001 to July
      2004. The hospital course, endocrinological function, radiographic imaging, and
      outpatient follow-up were retrospectively reviewed for each patient. RESULTS: The
      mean volume of these lesions was 31.5 cm(3) (range, 10.3-168 cm(3)). Tumor
      pathologies included 2 craniopharyngiomas, 16 functional, and 46 nonfunctional
      pituitary adenomas. Suprasellar extension of tumor was evident in all patients
      and 10 had cavernous sinus invasion. Gross total resection was achieved in 30
      patients, near-gross total in 6 patients, and subtotal resection in 26 patients.
      Eight patients (12.5%) demonstrated postoperative complications, with diabetes
      insipidus for less than 1 year (n = 4) being the most common. There was no
      incidence of CSF leak, new panhypopituitarism, or worsened vision. Five patients
      (7.8%) had tumor residual requiring radiation therapy. Additionally, after a mean
      clinical follow-up of 24.5 months, 4 patients (6.3%) demonstrated recurrent
      disease. CONCLUSIONS: Direct endonasal transsphenoidal surgery enables safe and
      effective resection of large sellar masses while maintaining a favorable
      morbidity profile.

PMID- 18094938
TI  - Advantages of using newly developed quartz contact lens with slit illumination
      from operating microscope.
AB  - The purpose of this article is to report the characteristics and advantages of
      using a newly designed quartz contact lens with slit illumination from an
      operating microscope for intraocular surgery. The new contact lens is made of
      quartz. The lens is convex-concave and is used in combination with slit
      illumination from an operating microscope. The optical properties of quartz make
      this lens less reflective with greater transmittance. The combination of a quartz
      contact lens with slit illumination provided a brighter and wider field of view
      than conventional lenses. This system enabled us to perform bimanual vitrectomy
      and scleral buckling surgery without indirect ophthalmoscope. Small intraocular
      structures in the posterior pole or in the periphery were detected more easily.
      In conclusion, the newly designed quartz lens with slit beam illumination from an
      operating microscope provided a bright, clear and wide surgical field, and
      allowed intraocular surgery to be performed more easily.

PMID- 18094939
TI  - Regression of severe corneal stromal neovascularization with topical cyclosporine
      0.05% after penetrating keratoplasty for fungal corneal ulcer.
AB  - PURPOSE: To report regression of corneal stromal neovascularizations with the use
      of topical cyclosporine 0.05% in a corneal transplant patient performed for
      fungal corneal ulcer. DESIGN: Case report. METHODS: A 14-year-old boy treated for
      fungal corneal ulceration developed 360 degrees corneal stromal
      neovascularization peroperatively. Topical cyclosporine 0.05% was used to
      decrease the risk of rejection. RESULTS: The neovascularizations regressed
      totally within 2 months and no signs of graft rejection were present at 6 months
      follow up. CONCLUSION: Topical cyclosporine 0.05% may result in regression of
      stromal corneal neovascularizations and help to reduce the risk of graft
      rejection in selected cases.

PMID- 18094940
TI  - Early OCT changes of neuroretinal foveal thickness after first versus repeated
      PDT in AMD.
AB  - PURPOSE: To compare early optical coherence tomography (OCT) changes in
      neuroretinal foveal thickness (NFT) after first versus repeated photodynamic
      treatment (PDT) in eyes with choroidal neovascularization (CNV) due to age
      related macular degeneration (AMD). METHODS: This is a prospective comparative
      case series study. Consecutive AMD patients, treated with PDT due to subfoveal
      CNV, were enrolled. The eyes were divided into two groups: group A included eyes
      that had received the first initial treatment, and group B included eyes that had
      received repeated treatment. All eyes underwent serial examinations with OCT:
      prior to PDT, 1 h, and 3 months after the PDT. The primary outcome measure was
      early OCT change in NFT after PDT. RESULTS: Thirty-three eyes of 33 patients were
      included in this study; 16 in group A and 17 in group B. Optical coherence
      tomography showed a significant increase in NFT 1 h after PDT, as compared to pre
      treatment status, in group A eyes (P = 0.008) but not in group B eyes (P =
      0.731). Subretinal fluid was increased in both groups (93.8% and 88.2%,
      respectively), whereas intraretinal fluid was remarkably more increased in group
      A eyes (88%) than in group B eyes (59%). CONCLUSION: Early change in NFT,
      demonstrated on OCT, indicates that PDT causes different retinal response in
      primary versus repeated treatment of PDT for CNV due to AMD.

PMID- 18094941
TI  - Statins in acute brain injury: getting the cart before the horse.

PMID- 18094942
TI  - Dermal immunopathology: from genetics to effector mechanisms.

PMID- 18094943
TI  - Cutaneous perspectives on adaptive immunity.
AB  - The skin, situated at the critical juncture between the host and the environment,
      is subject to a variety of potentially damaging agents including microbial
      organisms, toxins, and gene-altering radiation. Diverse immunocytes, including
      those resident in the skin and those with the capacity to traffic to and from the
      skin, direct two major types of immune responses: more immediate and less
      discriminate defenses (so-called innate immunity), and more coordinated and
      antigen-specific responses (so-called adaptive immunity). This review will focus
      on features of the adaptive immune system operative within the skin and consider
      the roles of dendritic cells, lymphocytes, endothelial cells, chemokines, and
      cytokines. In particular, the major subsets of T cells and the mechanisms by
      which they endow and regulate the features of adaptive immunity in the skin will
      be considered, including: the efficient surveillance and recognition of diverse
      foreign-antigens while limiting reactivity against self-antigens; differentiation
      into various effector cells capable of inducing apoptosis of infected/damaged
      cells and/or directing the activities of other immunocytes; and providing for
      immunologic memory whereby subsequent antigen exposure elicits a rapid and
      augmented antigen-specific response. It is within this context that the adaptive
      immune system will be considered for its role in the skin in mediating microbial
      defense with direct relevance to tumor immunosurveillance and inflammatory
      disease.

PMID- 18094944
TI  - Dendritic cells and contact dermatitis.
AB  - Contact dermatitis is a biological response to simple chemicals in the skin.
      Although it is well known that allergic contact dermatitis is mediated by the
      immune system, it is still uncertain whether it is a kind of protective response
      or it is simply an unnecessary response. We have demonstrated the following: (1)
      haptens activate Langerhans cells in the initiation phase of murine allergic
      contact dermatitis in vivo, (2) haptens activate human monocyte-derived dendritic
      cells in vitro, (3) the activation of dendritic cells by haptens is primarily
      mediated by the activation of p38 mitogen-activated protein kinase (MAPK), and
      (4) the activation of p38 MAPK is mediated by stimulation related to an imbalance
      of intracellular redox. Based on these observations, we will discuss the
      biological significance of contact dermatitis. In addition, we will review some
      up-to-date findings on Langerhans cell biology.

PMID- 18094945
TI  - Current aspects of innate and adaptive immunity in atopic dermatitis.
AB  - Atopic dermatitis (AD) is a highly pruritic, chronic, multifactorial skin disease
      predisposing to bacterial and viral infections based on abnormalities of the
      innate and acquired immune system. The innate system quickly mobilizes an
      inflexible, standardized first-line response against different pathogens.
      Epidermal barrier dysfunction results in increased protein allergen penetration
      through the epidermis and predisposes to secondary skin infections. Two loss-of
      function mutations in the epidermal filaggrin gene are associated with AD.
      Langerhans cells and inflammatory dendritic epidermal cells (IDEC) express high
      affinity IgE receptors, which are functional in IgE-mediated antigen
      presentation. Inducible antimicrobial peptides including the antiviral
      cathelicidin and the antibacterial beta-defensins show defective upregulation in
      lesional AD skin. The desmosomal protein nectin-1 is unmasked in AD lesions, thus
      becoming a relevant herpes simplex virus (HSV) entry receptor. Type I IFN
      producing plasmacytoid dendritic cells are decreased and dysfunctional in AD
      skin, predisposing the patients to viral skin infections. Molluscum contagiosum
      virus produces a unique IL-18 binding protein to evade antiviral defense
      mechanisms. Innate and adaptive immunity do not simply coexist but are linked to
      one another in a complex network of skin immunobiology.

PMID- 18094947
TI  - A perspective of pemphigus from bedside and laboratory-bench.
AB  - Pemphigus represents a distinct organ-specific acquired autoimmune disease
      characterized by intra-epidermal blistering, which is induced by autoantibodies
      against desmosomal cadherins, desmoglein 1 (Dsg1), and Dsg3. Pemphigus is
      currently divided into three distinct varieties, i.e., pemphigus vulgaris (PV),
      pemphigus foliaceus (PF) and other variants of pemphigus (mostly associated with
      inflammation), depending on clinical features, the level of separation in the
      epidermis, and immunologic characteristics of auto-antigens. Blistering
      pathomechanisms differ for each of the types of pemphigus. Pemphigus, which
      results from autoantibodies against desmogleins and possibly to other proteins,
      binds to the cell surface antigens. This binding may cause steric hindrance to
      homophilic adhesion of desmogleins, and may, in turn, lead to internalization of
      desmogleins and inhibition of desmogleins' integration into desmosomes, resulting
      in the formation of Dsg3-depleted desmosomes in PV or Dsg1-depleted desmosomes in
      PF. Furthermore, PV-IgG activates an "outside-in" signaling pathway to induce
      disassembly of desmosomal components from the inside of the cells by
      phosphorylation of proteins, including Dsg3. On the other hand, Pemphigus-IgG
      augmented signaling pathways may be linked to the secretion of cytokines such as
      in case of pemphigus herpetiformis and chemokines that initiate or activate
      inflammation. In this article, the classification of pemphigus and the
      characteristic pathomechanisms for acantholysis will be reviewed, with particular
      emphasis on the molecular and biochemical cell biology of these diseases.

PMID- 18094946
TI  - Immunopathogenesis of psoriasis.
AB  - Investigations into the cause and treatment of psoriasis remain at the forefront
      of basic and applied clinical research efforts around the world. The purpose for
      this review is to provide an up-to-date synopsis of recent progress in ten
      sections exploring the immunological and inflammatory basis for psoriasis. Given
      the breadth of this topic in investigative skin biology and frequent paradigm
      shifts, it should not be surprising that the bibliography contains more than 150
      references; many of which have been published in the last 5 years. Whereas
      considerable progress has been made into the immunopathogenesis of psoriasis,
      many fundamentally important questions remain regarding the role of cells located
      in both epidermal and dermal compartments. Attempts to characterize various
      animal models of psoriasis, delineation of the mechanism of action for biological
      agents, and consideration of molecular links between skin inflammation and
      various extracutaneous comorbidities are likely to continue challenging
      investigators and clinicians for many years to come.

PMID- 18094948
TI  - The pathophysiology of bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is a blistering skin disease characterized by an
      autoimmune response to 2 hemidesmosomal proteins within the dermal-epidermal
      junction, designated BP180 and BP230. While BP230 localizes intracellularly and
      associates with the hemidesmosomal plaque, BP180 is a transmembrane glycoprotein
      with an extracellular domain. Most BP patients have autoantibodies binding to an
      immunodominant region of BP180, the noncollagenous 16A domain (NC16A), which is
      located extracellularly close to the transmembrane domain of the protein.
      Autoreactive T and B cell responses to BP180 have been found in patients with BP.
      Passive transfer of antibodies to the murine BP180 ectodomain triggers a
      blistering skin disease in mice that closely mimics human BP. Lesion formation in
      this animal model depends upon complement activation, mast cell degranulation and
      accumulation of neutrophils and eosinophils. Patients' autoantibodies to BP180
      induce dermal-epidermal separation in cryosections of human skin when co
      incubated with leukocytes. The loss of cell-matrix adhesion is mediated by
      proteinases released by granulocytes. The increased knowledge of the
      pathophysiology of BP should facilitate the development of novel therapeutic
      strategies for this disease.

PMID- 18094950
TI  - Target cells in graft-versus-host disease: implications for cancer therapy.
AB  - Acute graft-versus-host disease (GVHD) conceptually may be divided into three
      evolutionary stages: allostimulation, effector cell homing to specific tissues,
      and cellular targeting and injury. Surprisingly, little is known regarding the
      targeting stage of GVHD. Recently, we have learned that epithelial target cell
      injury is mediated by specific subpopulations of effector T cells that may be
      identified based on Vbeta family expansion during allostimulation. Antibody
      probes specific for these Vbeta families have permitted precise identification of
      effector cell homing patterns. In squamous epithelium, allospecific T cells
      selectively home to basal cell layer subpopulations that express cytokeratin 15
      (CK15) and that undergo target cell injury via apoptosis. Interestingly, these
      target cells coincide with basal layer subpopulations that have properties of
      epithelial stem cells and that normally express an apoptosis-resistant genomic
      profile. Accordingly, epithelial cell injury in GVHD appears to involve selective
      targeting of stem-cell subpopulations via conversion from an anti-apoptotic to a
      pro-apoptotic phenotype. Understanding of the mechanism(s) of this conversion
      could facilitate development of translationally relevant approaches to shielding
      target cells from injury in GVHD. Moreover, determination of how putative
      apoptosis-resistant stem cells may be rendered vulnerable to immune-mediated
      targeting has implications potentially relevant to more directed
      immunotherapeutic approaches focused at elimination of neoplastic (cancer) stem
      cells.

PMID- 18094949
TI  - Pathophysiology of cutaneous lupus erythematosus.
AB  - Cutaneous lupus erythematosus (LE; syn LE-specific skin disease) is an autoimmune
      disease with well-defined skin manifestations often accentuated in a
      photodistribution and frequently associated with specific autoantibodies. These
      clinical observations have led to numerous laboratory studies related to the role
      of ultraviolet light, as well as studies of the cascade of immunologic events
      involved in the pathogenesis of cutaneous LE. We discuss the epidemiologic,
      clinical, and laboratory findings of cutaneous LE, including the classification
      of disease subsets. We review the evidence for abnormal photoreactivity in LE
      with an overview of the cellular, molecular, and genetic factors that may
      underlie this abnormality. As there is yet no convincing animal model of
      cutaneous LE, many studies remain descriptive in nature. To arrive at an
      understanding of the potential mechanisms underlying the development of cutaneous
      lupus, we discuss the role of ultraviolet light-mediated induction of apoptosis,
      antigen presentation, genetic factors, and mediators of inflammation. In
      addition, we consider the role and importance of humoral and cellular factors,
      synthesizing the current understanding of the pathophysiology of cutaneous lupus.

PMID- 18094951
TI  - A complex interaction between drug allergy and viral infection.
AB  - A relationship between viral infections and the simultaneous or subsequent
      development of drug rashes has been observed in a number of clinical situations.
      We have recently provided evidence to indicate an intimate relationship between
      reactivation of human herpesvirus 6 (HHV-6) and the development of a severe
      systemic hypersensitivity reaction referred to as drug-induced hypersensitivity
      syndrome (DIHS). This syndrome has several unique features that cannot be
      explained by a drug etiology; they include its delayed onset, paradoxical
      worsening of clinical symptoms after discontinuation of the causative drugs, and
      a step-wise development of several organ system failures long after clinical
      resolution. Many aspects of this syndrome suggest close similarities between DIHS
      and graft-versus-host disease (GVHD). Indeed, a wide variety of complications
      frequently occurring in GVHD, such as autoimmune diseases, is often observed
      during the course of this syndrome and even long after clinical resolution. Our
      recent studies have shown that in DIHS sequential reactivations of several
      herpesviruses (HHV-6, HHV-7, Epstein-Barr virus, and cytomegalovirus) can be
      detected coincident with various clinical symptoms in the same order as
      demonstrated in GVHD. Thus, not only the timing but also the order in which these
      herpesviruses can be reactivated in the host would be crucial determinant of
      outcomes of the disease. Our results indicate the importance of recognizing DIHS
      and other drug rashes associated with viral infections at risk of eventually
      developing autoimmune diseases.

PMID- 18094952
TI  - Chronic urticaria: recent advances.
AB  - Chronic urticaria is an umbrella term, which encompasses physical urticarias,
      chronic "idiopathic" urticaria and urticarial vasculitis. It is important to
      recognize patients with physical urticarias as the investigation and treatment
      differs in important ways from patients with idiopathic chronic urticaria or
      urticarial vasculitis. Although relatively uncommon, urticarial vasculitis is an
      important diagnosis to make and requires histological confirmation by biopsy.
      Underlying systemic disease and systemic involvement, especially of the kidneys,
      should be sought. It is now recognized that chronic "idiopathic" urticaria
      includes a subset with an autoimmune basis caused by circulating autoantibodies
      against the high affinity IgE receptor (FceR1) and less commonly against IgE.
      Although the autologous serum skin test has been proven useful in prompting
      search for and characterization of circulating wheal-producing factors in chronic
      urticaria, its specificity as a screening test for presence of functional anti
      FceR1 is low, and confirmation by demonstration of histamine-releasing activity
      in the patient's serum must be the benchmark test in establishing this diagnosis.
      Improved screening tests are being sought; for example, ability of the chronic
      urticaria patient's serum to evoke expression of CD 203c on donor human basophils
      is showing some promise. The strong association between autoimmune thyroid
      disease and autoimmune urticaria is also an area of ongoing research. Drug
      treatment continues to be centered on the H1 antihistamines, and the newer second
      generation compounds appear to be safe and effective even in off-label dosage.
      Use of systemic steroids should be confined to special circumstances such as
      tapering regimens for acute flare-ups. Use of leukotriene antagonists is becoming
      popular, but the evidence for efficacy is conflicting. Cyclosporin is also
      effective and can be used in selected cases of autoimmune urticaria, and it is
      also effective in non-autoimmune cases, although less so.

PMID- 18094953
TI  - Mast cells and immunological skin diseases.
AB  - Mast cells play an important role in both adaptive and innate immunity, and a
      large body of literature demonstrates their functions in skin immunity. This
      article reviews the literature on the role of this cell type in the pathogenesis
      of a number of immunological skin diseases, including contact dermatitis, atopic
      dermatitis, immunobullous disease, scleroderma, and chronic graft-vs.-host
      disease. In all these diseases, mast cells are noted to increase in number and
      undergo degranulation in the affected skin, and in some cases, their specific
      mediators are detected. Elucidation of the contribution of mast cells to the
      pathogenesis of these diseases has been aided significantly by the use of animal
      models, especially mouse models. The studies of mast cell-deficient mice in
      conjunction with normal congenic mice have been particularly fruitful, although
      in some cases, such as contact dermatitis, a definitive conclusion has not been
      achieved despite extensive efforts. The role of mast cells in atopic dermatitis
      has also been suggested by studies of gene polymorphism, which have linked some
      of the mast cell-related genes to the disease. In the case of scleroderma and
      chronic graft-vs.-host disease, the function of mast cells in fibrosis is further
      supported by the ability of these cells and their mediators to induce activation
      and proliferation of fibroblasts. Therapies targeting mast cells may prove
      beneficial for treatment of these inflammatory and autoimmune diseases.

PMID- 18094954
TI  - Candidate genes and QTLs for fruit ripening and softening in melon.
AB  - Different factors affect the quality of melon fruit and among them long shelf
      life is critical from the consumer's point of view. In melon, cultivars showing
      both climacteric and non-climacteric ripening types are found. In this study we
      have investigated climacteric ripening and fruit softening using a collection of
      near-isogenic lines (NILs) derived from the non-climacteric melon parental lines
      PI 161375 (SC) and "Piel de Sapo" (PS). Surprisingly, we found that QTL eth3.5 in
      NIL SC3-5b induced a climacteric-ripening phenotype with increased respiration
      and ethylene levels. Data suggest that the non-climacteric phenotypes from PI
      161375 and "Piel de Sapo" may be the result of mutations in different genes.
      Several QTLs for fruit flesh firmness were also detected. Candidate genes
      putatively involved in ethylene regulation, biosynthesis and perception and cell
      wall degradation were mapped and some colocations with QTLs were observed. These
      results may provide additional data towards understanding of non-climacteric
      ripening in melon.

PMID- 18094955
TI  - Mendelian randomisation studies of type 2 diabetes: future prospects.

PMID- 18094956
TI  - No, the glycaemic target in the critically ill should not be < or = 6.1 mmol/l.

PMID- 18094957
TI  - Global gene expression profiling and histochemical analysis of the developing
      human fetal pancreas.
AB  - AIMS/HYPOTHESIS: An immunohistochemical and genomic analysis of human pancreatic
      development from 9-23 weeks of fetal age was undertaken to provide a comparative
      analysis of human and murine islet development. METHODS: Human fetal pancreases
      obtained at gestational ages 9-23 weeks were processed in parallel for
      immunohistochemistry and gene expression profiling by Affymetrix microarrays.
      RESULTS: By 9-11 weeks, the pancreas was made up principally of mesenchymal
      tissue infiltrated by branched epithelial structures containing scattered hormone
      negative neurogenin3-positive endocrine cells. Protoacinar structures emerged by
      15-19 weeks, along with clusters of endocrine cells producing either glucagon or
      insulin. By 20-23 weeks, vascularised islet-like structures appeared. More than
      70% of endocrine cells produced a single hormone at any age. Analysis of Ki67
      immunoreactivity showed that the replicative rate of endocrine cells was low and
      suggested that the endocrine expansion was derived from hormone-negative
      precursors. Insulin, glucagon, somatostatin, ghrelin and pancreatic polypeptide
      transcripts were present at 9-10 weeks and increased progressively, commensurate
      with the expansion of endocrine cell volume. The human equivalent of a mouse
      endocrine secondary transition was not evident, neither in terms of morphology
      nor in dramatic changes in endocrine-specific transcriptional regulators. By
      contrast, exocrine genes showed a marked transition at around 11 weeks,
      associated with a greater than sixfold increase in exocrine gene transcripts.
      CONCLUSIONS/INTERPRETATION: The observed extension of terminal differentiation of
      human endocrine tissue into late gestation is in contrast with findings in the
      mouse. It indicates that the human fetal pancreas could provide an abundant islet
      precursor cell population that could be expanded ex vivo for therapeutic
      transplantation.

PMID- 18094958
TI  - Azospirillum brasilense Sp7 produces an outer-membrane lectin that specifically
      binds to surface-exposed extracellular polysaccharide produced by the bacterium.
AB  - Azospirillum sp promotes the growth of many important crop plants. We
      demonstrated lectin binding activity in outer-membrane protein extracts of A.
      brasilense Sp7 by hemagglutination assays. The lectin specifically recognised the
      exopolysaccharide (EPS) produced by aggregated cells. Affinity chromatography
      using EPS-Sepharose was used to identify a 67 kDa outer-membrane lectin (OML)
      that recognised a binding region in the extracellular polysaccharide. Results
      show the specific recognition and binding between EPS and OML. The potential
      relationship between cell-to-cell aggregation and the OML-EPS interaction is
      discussed.

PMID- 18094959
TI  - New plasmid-mediated resistances to antimicrobial agents.

PMID- 18094961
TI  - Rapid response behavior, at room temperature, of a nanofiber-structured TiO2
      sensor to selected simulant chemical-warfare agents.
AB  - A chemical prototype sensor was constructed based on nanofiber-structured TiO2
      and highly sensitive quartz resonators. The gas-sensing behavior of this new
      sensor to selected simulant warfare agents was investigated at room temperature.
      Results showed rapid response and good reversibility of this sensor when used
      with high-purity nitrogen. This provides a simple approach to preparation of
      materials needed as chemical sensors for selected organic volatiles or warfare
      agents.

PMID- 18094960
TI  - Alleviation by Hypericum perforatum of the stress-induced impairment of spatial
      working memory in rats.
AB  - It is recognized that chronic stress is an important risk factor for the
      development of several cognitive impairments involving working memory. Working
      memory refers to the memory in which the information to be remembered changes
      from trial-to-trial and should be assessed in a task able to detect retrieval of
      that information. In the present study, we tested the hypothesis that preventive
      administration of Hypericum perforatum (also named St John's wort) may counteract
      the working memory impairments caused by repeated stress. Specifically, we
      attempted to characterize the preventive action of long-lasting treatment with St
      John's wort (350 mg/kg, p.o.) on the spatial working memory impairments caused by
      chronic restraint stress (2 h daily for 21 days) or durable medication with
      exogenous corticosterone (5 mg/kg, s.c.) in male Wistar rats. Spatial working
      memory was tested in Barnes maze (BM) and in the Morris water maze (MWM). We
      found that H. perforatum prevented the deleterious effects of both chronic
      restraint stress and prolonged corticosterone on working memory measured in both
      tests. The herb significantly improved hippocampus dependent spatial working
      memory in comparison with control (p < 0.01) and alleviated some other negative
      effects of stress on cognitive functions.

PMID- 18094962
TI  - Processing of inconsistent emotional information: an fMRI study.
AB  - Previous studies investigating the anterior cingulate cortex (ACC) have relied on
      a number of tasks which involved cognitive control and attentional demands. In
      this fMRI study, we tested the model that ACC functions as an attentional network
      in the processing of language. We employed a paradigm that requires the
      processing of concurrent linguistic information predicting that the cognitive
      costs imposed by competing trials would engender the activation of ACC. Subjects
      were confronted with sentences where the semantic content conflicted with the
      prosodic intonation (CONF condition) randomly interspaced with sentences which
      conveyed coherent discourse components (NOCONF condition). We observed the
      activation of the rostral ACC and the middle frontal gyrus when the NOCONF
      condition was subtracted from the CONF condition. Our findings provide evidence
      for the involvement of the rostral ACC in the processing of complex competing
      linguistic stimuli, supporting theories that claim its relevance as a part of the
      cortical attentional circuit. The processing of emotional prosody involved a
      bilateral network encompassing the superior and medial temporal cortices. This
      evidence confirms previous research investigating the neuronal network that
      supports the processing of emotional information.

PMID- 18094964
TI  - Multimodality imaging of Candida tropicalis myositis.
AB  - Fungal myositis is a rare entity that has been described in immunocompromised
      patients. We present a boy with biopsy proven fungal myositis who was examined
      with multiple imaging modalities. MR imaging proved to be very effective for
      diagnostic purposes, while US imaging was able to provide guidance for biopsy.

PMID- 18094963
TI  - Influence of pathologic and simulated visual dysfunctions on the postural system.
AB  - Visual control has an influence on postural stability. Whilst vestibular,
      somatosensoric and cerebellar changes have already been frequency analytically
      parameterized with posturography, sufficient data regarding the visual system are
      still missing. The aim of this study was to evaluate the influence of pathologic
      and simulated visual dysfunctions on the postural system by calculating the
      frequency analytic representation of the visual system throughout the frequency
      range F1 (0.03-0.1 Hz) of Fourier analysis. The study was divided into two parts.
      In the first part, visually handicapped subjects and subjects with normal vision
      were investigated with posturography regarding postural stability (stability
      effect, Fourier spectrum of postural sway, etc.) with open and closed eyes. The
      visually impaired and the normal group differed significantly in the frequency
      range F1 (p = 0.002). Significant differences of the postural stability between
      both groups were found only in the test position with open eyes (NO). The healthy
      group showed a significant loss of stability, whereas the impaired group showed
      an increased stability due to sufficient somatosensoric processes. Visually
      handicapped persons can compensate the visual information deficit through
      improved peripheral-vestibular and somatosensoric perception and cerebellar
      processing. In the second part, subjects with normal vision were examined under
      simulated visual conditions, e.g., hyperopia (3.0 D), reduced visual acuity (VA =
      20/200), yoke prisms (4 cm/m) and pursuits (pendulum). Changes in postural
      parameters due to simulations have been compared to a standard situation (open
      eyes [NO], fixation distance 3 m). Visual simulations showed influence on
      frequency range F1. Compared to the standard situation, significant differences
      have been found in reduced visual acuity, pursuits and yoke prisms. A loss of
      stability was measured for simulated hyperopia, pendulum and yoke prisms base
      down. Stability regulation can be understood as a multi-sensoric process by the
      visual, vestibular, somatosensoric and cerebellar system. Reduced influence of a
      single subsystem is compensated by the other subsystems. Obviously the main part
      of reduced visual input is compensated by the vestibular system. Moreover, the
      body sway, represented by the stability indicator, increased in this situation.

PMID- 18094965
TI  - High-level expression of an antimicrobial peptide histonin as a natural form by
      multimerization and furin-mediated cleavage.
AB  - Direct expression of an antimicrobial peptide (AMP) in Escherichia coli causes
      several problems such as the toxicity of AMP to the host cell, its susceptibility
      to proteolytic degradation, and decreased antimicrobial activity due to the
      additional residue(s) introduced after cleavage of AMPs from fusion partners. To
      overcome these problems and produce a large quantity of a potent AMP histonin
      (RAGLQFPVGKLLKKLLKRLKR) in E. coli, an efficient expression system was developed,
      in which the toxicity of histonin was neutralized by a fusion partner F4 (a
      truncated fragment of PurF protein) and the productivity was increased by a
      multimeric expression of a histonin gene. The expression level of the fusion
      proteins reached a maximum with a 12-mer of a histonin gene. In addition, because
      of the RLKR residues present at the C terminus of histonin, furin cleavage of the
      multimeric histonin expressed produces an intact, natural histonin. The AMP
      activity of the histonin produced in E. coli was identical to that of a synthetic
      histonin. With our expression system, 167 mg of histonin was obtained from 1 l of
      E. coli culture. These results may lead to a cost-effective solution for the mass
      production of AMPs that are toxic to a host.

PMID- 18094966
TI  - Recommendations for the assessment and monitoring of skeletal manifestations in
      children with Gaucher disease.

PMID- 18094967
TI  - In vivo responses to vaccination with Mage-b, GM-CSF and thioglycollate in a
      highly metastatic mouse breast tumor model, 4T1.
AB  - Metastatic breast cancer is an important contributor to morbidity and mortality.
      Hence, new therapies are needed that target breast cancer metastases. Here, we
      focus on Mage-b as a possible vaccine target to prevent the development of breast
      cancer metastases, through activation of Mage-b-specific cytotoxic T lymphocytes
      (CTL). The syngeneic cell line 4T1, highly expressing Mage-b, was used as a pre
      clinical metastatic mouse breast tumor model. BALB/c mice received three
      preventive intraperitoneal immunizations with Mage-b DNA vaccine mixed with
      plasmid DNA, secreting granulocyte-macrophage colony stimulating factor (GM-CSF).
      In addition, antigen-presenting cells were more efficiently recruited to the
      peritoneal cavity by the injection of thioglycollate broth (TGB), prior to each
      immunization. Immunization with Mage-b/GM-CSF/TGB significantly reduced the
      number of metastases by 67% compared to the saline/GM-CSF/TGB and by 69% compared
      to the vector control/GM-CSF/TGB. Also, tumor growth was significantly reduced by
      45% in mice vaccinated with Mage-b/GM-CSF/TGB compared to the saline/ GM-CSF/TGB
      and by 47% compared to the control vector/ GM-CSF/TGB group. In vivo, the number
      of CD8 T cells significantly increased in the primary tumors and metastases of
      mice vaccinated with Mage-b/GM-CSF/TGB compared to the saline/GM-CSF/TGB and the
      control vector/ GM-CSF/TGB group, while the number of CD4 T cells significantly
      decreased. The combination of Mage-b, GM-CSF and TGB did not only induce
      significantly higher levels of IFNgamma in the lymph nodes of vaccinated compared
      to control mice, but also induced significantly higher expression levels of Fas
      ligand (FasL) in the primary tumors (expressing Fas protein constitutively),
      compared to the control mice. Whether the interaction between Fas and FasL may
      have contributed to the smaller tumors needs to be further analyzed.

PMID- 18094968
TI  - CD4 and CD8 T cell responses to tumour-associated Epstein-Barr virus antigens in
      nasopharyngeal carcinoma patients.
AB  - Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated tumour
      common in Southern Chinese populations, is a potentially important target for T
      cell-based immunotherapy. The tumour cells are HLA class I- and II-positive and
      express a limited subset of EBV latent proteins, namely the nuclear antigen EBNA1
      and the latent membrane proteins LMP2 and (in some cases) LMP1. To ask whether
      the tumour develops in the presence of a potentially protective host response or
      in its absence, we set out to determine the prevailing levels of CD4+ and CD8+ T
      cell memory to these proteins in NPC patients at tumour diagnosis. We first
      screened healthy Chinese donors against Chinese strain EBNA1, LMP1 and LMP2
      sequences in Elispot assays of interferon-gamma release and identified the
      immunodominant CD4+ and CD8+ epitope peptides presented by common Chinese HLA
      alleles. Then, comparing 60 patients with >70 healthy controls on peptide epitope
      mini-panels, we found that T cell memory to CD4 epitopes in all three proteins
      was unimpaired in the blood of patients at diagnosis. In most cases NPC patients
      also showed detectable responses to CD8 epitopes relevant to their HLA type, the
      one consistent exception being the absence in patients of a B*4001-restricted
      response to LMP2. We infer that NPC arises in patients whose prevailing levels of
      T cell memory to tumour-associated EBV proteins is largely intact; the
      therapeutic goal must therefore be to re-direct the existing memory repertoire
      more effectively against antigen-expressing tumour cells.

PMID- 18094969
TI  - Midterm results following revision surgery in clubfeet.
AB  - Relapse rates of surgically treated clubfeet are about 25%. We reviewed 43
      patients (57 feet) treated for relapsed clubfoot deformity between 1992 and 2001
      in our department. The average age of the patients at the time of revision
      surgery was 5.1 years, the mean follow-up was 6.6 years. Surgical therapy was
      performed using an algorithm according to age groups. The mean Atar score at
      follow-up was 77 points, representing a good outcome. Out of 57 feet, 20 (35%)
      were rated excellent, 24 (42%) good, 5 (9%) fair, and 8 (14%) poor. The number of
      previous surgical interventions had no influence on the outcome. Using an age
      related surgical algorithm, good postoperative results could be achieved in most
      of our patients, thus improving their functional situation. This emphasises the
      usefulness of the proposed algorithm in the difficult situation of recurrent
      clubfoot, while thorough analysis of the underlying deformity remains essential.

PMID- 18094971
TI  - Idiopathic hypertrophic cranial pachymeningitis treated by oral methotrexate: a
      case report and review of literature.
AB  - Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare clinical entity,
      characterized by a chronic inflammation causing thickening of the dura. Adequate
      therapeutic management is still a matter of debate. We present a patient with an
      IHCP, non-responsive to corticotherapy. Oral methotrexate was introduced (12.5 mg
      weekly) and total remission was observed after 6 weeks, both clinically and after
      neuro-imaging. We conclude that methotrexate can be effective and a therapeutical
      option in patients with IHCP who are resistant to corticotherapy or present major
      side-effects of chronic corticosteroids use.

PMID- 18094970
TI  - Difference in outcome of shoulder surgery between workers' compensation and
      nonworkers' compensation populations.
AB  - The purpose of this study was to review the association between compensation
      status and surgical outcome especially of the shoulder. Given the high prevalence
      of shoulder injuries in the workplace and the large proportion of workers
      compensation (WC) claims involving such injuries, it is worth examining the
      correlation between WC status and surgical outcome of the shoulder. All studies
      published in journals (MEDLINE and PubMed) from 1980 through 2007 on surgical
      interventions performed on the shoulder in which workers compensation status was
      documented and the postoperative functional outcome was compared according to
      that status were pooled for meta-analysis. This systematic review shows that
      compensation status of an individual receiving shoulder surgery is a consistent
      positive predictor of poor functional outcome. The majority of questions posed in
      the most commonly adopted shoulder-specific functional outcome measurement tools
      were subjective in nature and may account for part of the phenomenon.

PMID- 18094972
TI  - Aortic aneurysm sac pressure measurements after endovascular repair using an
      implantable remote sensor: initial experience and short-term follow-up.
AB  - The purpose of this single-center study was to report our initial experience with
      an implantable remote pressure sensor for aneurysm sac pressure measurement in
      patients post-endovascular aneurysm repair (EVAR) including short-term follow-up.
      A pressure sensor (EndoSure, Atlanta, GA) was implanted in 12 patients treated
      with different commercially available aortic endografts for EVAR. Pressure was
      read pre- and post-EVAR in the operating room. One-month follow-up (30 days+/-6
      days) was performed including sac pressure readings and IV contrast CT scans.
      Variables were compared using the paired Student's t test. An intraprocedure type
      I endoleak and a type-III endoleak were successfully treated resulting in
      decreasing sac pressures. In all patients, post-EVAR systolic sac pressure
      decreased by an average of 33% (P <or= 0.005) compared to pre-EVAR measurements.
      One-month follow-up demonstrated a 47% decrease in systolic sac pressure (P <or=
      0.05). On follow-up CT scans, the average maximum aneurysm diameter pre-EVAR was
      6.3+/-1.6 cm and post-EVAR 6.0+/-1.7 cm (P<or=0.05). The diameter of the aneurysm
      sac was larger only in one patient with a type-III endoleak. Remote sac pressure
      measurement may provide important information in addition to imaging and may help
      to reduce the number of follow-up CT scans.

PMID- 18094973
TI  - Time course of reversed cardiac remodeling after pulmonary endarterectomy in
      patients with chronic pulmonary thromboembolism.
AB  - To evaluate the time course of reversed remodeling after pulmonary endarterectomy
      (PEA) in patients with chronic thromboembolic pulmonary hypertension(CTPEH), we
      studied 22 patients (age: 60 +/- 13 years) with MRI immediately before, 1 month,
      3 months, and 6 months after PEA. MRI included assessment of biventricular
      function, aortic and pulmonary artery(PA) flow, and right ventricular (RV)
      overload using the ratio of RV-to-biventricular diameter. Except in one patient,
      who died 2 months post-surgery, clinical improvement occurred early after PEA
      (NYHA class: 3.3 +/- 0.6 to 1.5 +/- 0.8, p < 0.0001) with a decrease of systolic
      pulmonary artery pressures (79 +/- 14 to 44 +/- 14 mmHg, p < 0.0001). At 1 month
      post PEA, RV end-diastolic volumes decreased (198 +/- 72 to 137 +/- 59 ml, p <
      0.0001), and the RV ejection fraction (EF) improved (31 +/- 9 to 47 +/- 10%, p <
      0.0001). No further significant improvement in pulmonary pressures or RV function
      occurred at 3 months or 6 months. Although no significant change was found in LV
      volumes or function, aortic flow increased early after surgery. PEA had only a
      beneficial effect on right PA flow. RV overload decreased early after PEA (ratio
      RV-to-biventricular diameter: before: 0.67 +/- 0.04, after: 0.54 +/- 0.06, p <
      0.0001), showing a good correlation with the improvement in RVEF (r = 0.7, P <
      0.0001). In conclusion, reversed cardiac remodeling occurs early after PEA, to
      slow down after 1 month. At 6 months, cardiac remodeling is incomplete as
      witnessed by low-normal RV function and residually elevated PA pressures.

PMID- 18094974
TI  - Multidetector CT angiography in the assessment of peripheral arterial occlusive
      disease: accuracy in detecting the severity, number, and length of stenoses.
AB  - The purpose was to evaluate the accuracy of multidetector CT angiography (MD-CTA)
      in the morphologic assessment of peripheral arterial occlusive disease (PAOD)
      compared to digital subtraction angiography (DSA). Fifty consecutive patients
      referred for DSA of the peripheral arteries due to PAOD were prospectively
      included in this study and underwent 16-row MD-CTA prior to DSA. Maximum
      intensity projections and multipath curved planar reformations were created with
      a semi-automated toolbox. Twenty-one vascular segments were defined in each leg
      and compared to DSA findings with regard to gradation, length, and number of
      lesions. Mean sensitivity and specificity in the detection of significant
      stenoses (over 70%) were 100% and 99.5% in the iliac arteries, 97.4% and 99.0% in
      the femoro-popliteal arteries, and 98.3% and 99.8% in the infrapopliteal
      arteries, respectively. High kappa values for exact stenoses gradation (0.74-1),
      lesion length (0.74-1), and number of lesions (0.71-1) were reached by MD-CTA,
      indicating high agreement with DSA. Non-invasive MD-CTA is an accurate tool for
      the assessment of all treatment-relevant morphologic information of PAOD
      (gradation, length, and number of stenoses) compared to DSA.

PMID- 18094975
TI  - Interaction between descending input and thoracic reflexes for joint coordination
      in cockroach. II comparative studies on tethered turning and searching.
AB  - Tethered cockroaches turn from unilateral antennal contact using asymmetrical
      movements of mesothoracic (T2) legs (Mu and Ritzmannin J Comp Physiol A 191:1037
      1054, 2005). During the turn, the leg on the inside of the turn (the inside T2
      leg) has distinctly different motor patterns from those in straight walking. The
      transformation from walking to inside leg turning could be triggered by
      descending commands that alter a few critical reflexes that start a cascade of
      physical changes in leg movement or posture, leading to further alterations. This
      hypothesis has two implications: First, the descending activities must be able to
      influence thoracic reflexes. Second, one should be able to initiate the turning
      motor pattern in the absence of descending signals by mimicking a point farther
      down in the reflex cascade. We addressed the first implication in the companion
      paper. To examine the second implication, we compared kinematics and motor
      activities of the T2 leg during searching with that of inside leg turning. The
      reaching movements made during searching were found to be similar to the
      movements made by the inside leg during turning. Moreover, even after
      disconnecting the brain from the thoracic ganglia the reaching movements were
      similar. This observation is consistent with the second implication from the
      hypothesis.

PMID- 18094976
TI  - Interaction between descending input and thoracic reflexes for joint coordination
      in cockroach: I. descending influence on thoracic sensory reflexes.
AB  - Tethered cockroaches turn from unilateral antennal contact using asymmetrical
      movements of mesothoracic (T2) legs (Mu and Ritzmann in J Comp Physiol A 191:1037
      1054, 2005). During the turn, the leg on the inside of the turn (the inside T2
      leg) has distinctly different motor patterns from those in straight walking. One
      possible neural mechanism for the transformation from walking to inside leg
      turning could be that the descending commands alter a few critical reflexes that
      start a cascade of physical changes in leg movement or posture, leading to
      further alterations. This hypothesis has two implications: first, the descending
      activities must be able to influence thoracic reflexes. Second, one should be
      able to initiate the turning motor pattern without descending signals by
      mimicking a point farther down in the reflex cascade. We addressed the first
      implication in this paper by experiments on chordotonal organ reflexes. The
      activity of depressor muscle (Ds) and slow extensor tibia muscle (SETi) was
      excited and inhibited by stretching and relaxing the femoral chordotonal organ.
      However, the Ds responses were altered after eliminating the descending activity,
      while the SETi responses remain similar. The inhibition to Ds activity by
      stretching the coxal chordotonal organ was also altered after eliminating the
      descending activity.

PMID- 18094977
TI  - Far field scattering pattern of differently structured butterfly scales.
AB  - The angular and spectral reflectance of single scales of five different butterfly
      species was measured and related to the scale anatomy. The scales of the pierids
      Pieris rapae and Delias nigrina scatter white light randomly, in close agreement
      with Lambert's cosine law, which can be well understood from the randomly
      organized beads on the scale crossribs. The reflectance of the iridescent blue
      scales of Morpho aega is determined by multilayer structures in the scale ridges,
      causing diffraction in approximately a plane. The purple scales in the dorsal
      wing tips of the male Colotis regina act similarly as the Morpho scale in the
      blue, due to multilayers in the ridges, but the scattering in the red occurs as
      in the Pieris scale, because the scales contain beads with pigment that does not
      absorb in the red wavelength range. The green-yellow scales of Urania fulgens
      backscatter light in a narrow spatial angle, because of a multilayer structure in
      the scale body.

PMID- 18094978
TI  - Visual ecology of Indian carpenter bees I: light intensities and flight activity.
AB  - Bees are mostly active during the daytime, but nocturnality has been reported in
      some bee families. We studied temporal flight activity in three species of
      carpenter bees (genus Xylocopa) in relation to light intensities. X. leucothorax
      is diurnal, X. tenuiscapa is largely diurnal being only occasionally crepuscular,
      while X. tranquebarica is truly nocturnal. Occasional forays into dim light by X.
      tenuiscapa are likely to be due to the availability of richly rewarding
      Heterophragma quadriloculare (Bignoniaceae) flowers, which open at night. X.
      tranquebarica can fly even during the moonless parts of nights when light
      intensities were lower than 10(-5) cd m(-2), which makes this species the only
      truly nocturnal bee known so far. Other known dim-light species fly during
      crepuscular or moonlit periods. We compare eye and body sizes with other known
      diurnal and dim-light bees. We conclude that while extremely large ocellar
      diameters, large eye size:body size ratio, large number of ommatidia and large
      ommatidial diameters are all adaptations to dim-light foraging, these alone do
      not sufficiently explain the flights of X. tranquebarica in extremely dim light.
      We hypothesise that additional adaptations must confer extreme nocturnality in X.
      tranquebarica.

PMID- 18094979
TI  - Non-endoscopic percutaneous gastrostomy placement in children with recessive
      dystrophic epidermolysis bullosa.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB) is associated with high
      nutritional demands, esophageal strictures and dysphagia. About one quarter of
      the patients require gastrostomy tube placement to maintain adequate nutritional
      status. To minimize trauma to the skin and pharyngoesophageal mucosa caused by
      commonly used gastrostomy tube insertion techniques, we used a non-endoscopic,
      percutaneous, image-guided approach. This approach combines the use of ultrasound
      for mapping of the liver and spleen, water-soluble contrast enema to visualize
      the colon, and gastric insufflation to define the stomach. The gastrostomy tube
      is replaced by a low-profile button gastrostomy tube 10-12 weeks postoperatively.
      The five female patients reported in this series ranged in age from 6 to 9 years.
      They all tolerated the procedure well and no perioperative complications were
      encountered. All were able to tolerate feedings on postoperative day 1 and all
      underwent successful replacement of gastrostomy tubes by low-profile button
      tubes. Our experience suggests that a non-endoscopic, image-guided approach to
      gastrostomy tube placement offers a safe, effective, and minimally traumatic
      alternative to more commonly used approaches. It minimizes the risk of procedure
      related morbidity and leads to overall improvement in the quality of life. As
      such, we strongly recommend that it be included in the treatment armamentarium
      for patients with epidermolysis bullosa and nutritional failure.

PMID- 18094980
TI  - Histological assessment of bile lake formation after hepatic portoenterostomy for
      biliary atresia.
AB  - Bile lakes develop after hepatic portoenterostomy in some patients with biliary
      atresia, and have been regarded as an indication of poor prognosis. We reported
      that bile lakes have no epithelium of the bile duct on their wall, and are
      surrounded by bile ducts; however, the mechanism of bile lake formation is little
      known. We investigated histologically how bile ducts are formed using whole
      removed liver, and the characteristics of bile ducts around bile lakes. From
      April 1980 to July 2006, we encountered 84 patients with biliary atresia. Bile
      lakes were analyzed histologically in 11 patients who underwent liver
      transplantation in our hospital. Bile lakes had a fibrotic cyst wall and lacked
      epithelia. In most cases, bile stasis, calculi formation, damaged bile ducts, and
      invasion of inflammatory cells were observed around the bile lakes. Bile ducts
      around bile lakes were not stained by CD56, but bile ducts around liver lobuli
      were stained by CD56. The present study speculates that bile lakes would arise
      from original bile ducts, which are damaged, and fuse together after calculi are
      formed in bile ducts.

PMID- 18094981
TI  - A cyclic testing comparison of FasT-Fix and RapidLoc devices in human cadaveric
      meniscus.
AB  - INTRODUCTION: Cyclic testing may provide a more valid depiction of how
      arthroscopic meniscal repairs will withstand the forces of activities of daily
      living (ADLs) and therapeutic exercises early post-surgery than single cycle load
      to failure testing. This study compared the meniscal fixation provided by
      vertically or horizontally placed FasT-Fix devices to horizontally placed
      RapidLoc devices under submaximal cyclic test conditions. MATERIALS AND METHODS:
      Eighteen human cadaveric menisci were divided into three groups of six specimens.
      A scalpel was used to create a 2 cm lesion at 3 mm from the outer edge of the
      posterior third of each specimen. Merselene tape loops were placed around each
      side of the lesion and the tears were repaired using two vertical FasT-Fix, two
      horizontal FasT-Fix, or two RapidLoc devices. Cyclic testing (5-50 N at 1 Hz for
      500 cycles) was performed on a servo hydraulic device. One-way ANOVA and Scheffe
      post-hoc tests were used to evaluate group differences (P < 0.05). RESULTS: The
      vertical FasT-Fix group had less displacement over the initial ten loading cycles
      compared to the RapidLoc group (P = 0.004), but did not differ from the
      horizontal FasT-Fix group (P = 0.07). At 50, 100, 200, 300, 400, and 500 cycles,
      the vertical FasT-Fix group had less displacement than the horizontal FasT-Fix or
      RapidLoc groups (P < or = 0.004). At each interval the vertical FasT-Fix group
      had greater relative stiffness than the other groups (P < or = 0.009).
      CONCLUSIONS: The vertical FasT-Fix group had comparatively less displacement
      (primarily repair site gapping) and greater relative stiffness.

PMID- 18094982
TI  - Revascularisation during fracture healing with soft tissue injury.
AB  - INTRODUCTION: The purpose of our study was to quantitatively assess changes in
      the revascularisation process in the fracture gap and in adjacent regions during
      the course of healing of diaphyseal fractures with and without closed soft tissue
      injury. METHODS: In a rat model (fracture n = 26; fracture with closed soft
      tissue crush n = 26) revascularisation was assessed in a long-term study with
      regional mapping by laser Doppler flowmetry, the healing outcome being
      mechanically tested after 4 weeks. Fracture and soft tissue crush were performed
      by modified controlled impact device. RESULTS: No differences in blood
      circulation were observed at the fracture gap between the study groups up to day
      28. In the proximal region of the fracture, the blood circulation in the group
      with additional soft tissue trauma was down to the baseline throughout the
      investigation period while the values in the fracture group led to a
      hyperperfusion after 3 and 7 days. In the distal part at day 1, the blood flow
      was strongly depressed after fracture, while microcirculation with an additional
      soft tissue trauma showed only a moderate decline. The reduction of blood
      circulation in the soft tissue corresponded to the extent of trauma. Mechanical
      testing demonstrated no significant difference in failure load or in flexural
      rigidity. CONCLUSION: Our results indicate that damage severe soft tissue does
      not adversely affect the fracture healing process. Furthermore, the present
      findings suggest that a partly destroyed bone-soft tissue interaction resulting
      in only a temporary and slight reduction of the extraosseous blood supply might
      have no deteriorating effect on fracture healing outcome. A possible delay in
      healing is not observed during the first 4 weeks. Therefore, soft tissue damage
      without destruction of the bone-soft tissue interface is likely to have only a
      limited effect on fracture healing.

PMID- 18094983
TI  - The reverse shoulder prosthesis for primary and secondary treatment of proximal
      humeral fractures: a case report.
AB  - Humeral head fractures are very common among elderly people, often requiring
      shoulder arthroplasty. One requirement for good function after shoulder
      arthroplasty is an intact or at least reparable rotator cuff. In patients with
      multifractured and or osteoporotic tuberosities, refixation leads to the
      potential risk of redislocation and resorption of the tuberosities or coexisting
      irreparable rotator cuff tears lead to a high failure rate after implantation of
      traditional fracture prosthesis, whereas the reverse shoulder arthroplasty may
      provide better outcome. Here we report of a 79-year-old woman, who fractured both
      humeral heads at different times. Her right side was treated with a fracture
      prosthesis, which had to be converted after 2 years to a reverse shoulder
      prosthesis. Because of coexisting irreversible rotator cuff tear accompanying the
      second humeral head fracture on her left side, this patient was primarily treated
      with a reverse shoulder prosthesis. During the most recent follow up, 33 months
      after reverse shoulder arthroplasty on the left side and 39 months on the right
      side, the age- and gender-adapted constant score was 88 compared to 59 on the
      right side. The primary or secondary implantation of the reverse shoulder
      prosthesis in proximal humeral fractures has to be planned carefully, since long
      term results are still lacking and treatment options after failed reverse
      shoulder arthroplasty are few. Generally, primary implantation of traditional
      fracture prosthesis is indicated in most cases of humeral head fractures; but in
      carefully selected cases primary reverse shoulder arthroplasty may be superior
      and lead to better outcome. Therefore, future research should be conducted to
      find criteria where the reverse shoulder arthroplasty is indicated as first line
      treatment of proximal humeral head fractures in elderly patients.

PMID- 18094984
TI  - Demographics of extra-articular calcaneal fractures: including a review of the
      literature on treatment and outcome.
AB  - INTRODUCTION: Extra-articular calcaneal fractures represent 25-40% of all
      calcaneal fractures and an even higher percentage of up to 60% is seen in
      children. A disproportionately small part of the literature on calcaneal
      fractures involves the extra-articular type. The aim of this study was to
      investigate the incidence of extra-articular calcaneal fractures in a Level 1
      trauma centre, define the distribution of the various types of fractures and
      compare patient demographics between extra- and intra-articular calcaneal
      fractures. In addition the literature was reviewed for the most common types of
      extra-articular calcaneal fractures with regard to incidence, treatment and
      clinical outcome. METHODS: The radiological records between 2003 and 2005 were
      reviewed for intra- and extra-articular calcaneal fractures. Patient gender
      distribution and age were compared. A literature search was conducted for the
      treatment of extra-articular calcaneal fractures. RESULTS: In this 3-year study
      period a total of 49 patients with 50 extra-articular calcaneal fractures and 91
      patients with 101 intra-articular fractures were identified. The median age for
      the first group was 32.7 years, and for the second group 40.3 years; P = 0.04.
      Male predominance was significantly less pronounced for extra-articular (63%)
      compared with intra-articular fractures (79%; P = 0.04). CONCLUSION: One-third of
      all calcaneal fractures are extra-articular. Significant differences exist
      between the intra- and extra-articular groups, in terms of lower age and male
      female ratio. The literature study shows inconsistencies in treatment options,
      but most extra-articular fractures are well manageable conservatively.

PMID- 18094985
TI  - HPV status and regional metastasis in the prognosis of oral and oropharyngeal
      cancer.
AB  - Prognostic factors are important for treatment decisions as they help adapt the
      therapy on a case-to-case basis. Nodal status, number of positive nodes, and
      presence of extracapsular spread are considered to be the important prognostic
      factors in head and neck cancer. Some studies suggest that human papillomavirus
      (HPV) status also influences the outcome of the treatment. This influence can be
      explained by the variation in tendency to develop regional metastases and by
      variation in the type of neck node involvement. The study objectives were to
      compare patients with HPV positive and HPV-negative tumors for survival and
      prevalence and type of regional metastasis, to identify prognostic factors and to
      test whether HPV presence is an independent factor of survival. The study
      included 81 patients treated by surgery including neck dissection for oral or
      oropharyngeal squamous cell cancer. A computerized medical report was completed
      for each patient. Analysis of the tumor specimen for the HPV DNA presence was
      done on paraffin-fixed tissue. HPV DNA detection and typing were performed by PCR
      with GP5+/GP6+BIO primers and reverse line blot hybridization. Overall, 64%
      (52/81) of tumors were HPV positive with 80% in the tonsillar site. HPV-positive
      patients had significantly better both overall (73 vs. 35%) (P=0.0112) and
      disease-specific (79 vs. 45%) (P=0.0015) survival rates than HPV-negative
      patients. No significant differences were found in the pN classification, in the
      number of positive nodes and the presence of extracapsular spread in the involved
      nodes between HPV positive and HPV-negative tumors. Multivariate analysis showed
      that significant prognostic factors of survival were the presence of HPV in the
      tumor, extracapsular spread and tumor size. HPV was the most significant
      prognostic factor in the studied group of patients with oropharyngeal tumors
      (HR=0.27, 95%CI 0.12-0.61) and possibly should be considered in treatment
      decisions.

PMID- 18094986
TI  - Dissection of a Y-autosome translocation in Cryptomys hottentotus (Rodentia,
      Bathyergidae) and implications for the evolution of a meiotic sex chromosome
      chain.
AB  - We describe the outcome of a comprehensive cytogenetic survey of the common mole
      rat, Cryptomys hottentotus, based on G and C banding, fluorescence in situ
      hybridisation and the analysis of meiotic chromosomes using immunostaining of
      proteins involved in the formation of synaptonemal complex (SCP1 and SCP3). We
      identified the presence of a Y-autosome translocation that is responsible for a
      fixed diploid number difference between males (2n = 53) and females (2n = 54), a
      character that likely defines the C. hottentotus lineage. Immunostaining,
      combined with C banding of spermatocytes, revealed a linearised sex trivalent
      with X(1) at one end and X(2) at the other, with evidence of reduced
      recombination between Y and X(2) that seems to be heterochromatin dependant in
      the C. hottentotus lineage. We suggest that this could depict the likely initial
      step in the differentiation of a true neo-X, and that this may mimic an early
      stage in the mammalian meiotic chain formation, an evolutionary process that has
      been taken to an extreme in a monotreme mammal, the platypus.

PMID- 18094987
TI  - Pulfrich's phenomenon in optic nerve hypoplasia.
AB  - BACKGROUND: Optic nerve hypoplasia (ONH) is a congenital deficiency of retinal
      ganglion cells and their axons that form the optic nerve. The condition is
      associated with visual deficits ranging from no light perception in severe cases,
      to vision within normal range in mild cases of ONH. We report here a case of mild
      ONH with normal vision and with visual symptoms relating to a spontaneously
      occurring Pulfrich effect. METHODS: A twelve-year-old girl presented with typical
      visual symptoms (veering to the right when walking, bumping into things)
      associated with the spontaneous Pulfrich effect. When asked to follow a bob
      suspended from a simple rigid pendulum swinging in the frontal plane, a clockwise
      ellipse was reported, indicative of a left-sided Pulfrich effect. This effect was
      neutralised by an 85% transmission ophthalmic tint placed before the right eye.
      The inter-ocular latency difference responsible for the illusion was calculated
      to be 0.88 +/- 0.55 ms. RESULTS: Fundus biometry showed an asymmetry in R and L
      optic nerve dimensions, the left being smaller than the right. Vision was normal
      in each eye, as were visual fields, colour vision and stereopsis. The affected
      eye showed normal flash and pattern VEPs and ERGs, except for a borderline
      reduction of the pattern ERG (PERG) to very small checks. CONCLUSIONS: A case of
      mild ONH with normal visual function in each eye resulted in a small inter-ocular
      delay associated with errors in visual perception consistent with a spontaneous
      Pulfrich effect. Wearing a pair of glasses with the right lens tinted eliminated
      these difficulties.

PMID- 18094988
TI  - Asbestos related diseases in Italy: an integrated approach to identify unexpected
      professional or environmental exposure risks at municipal level.
AB  - PURPOSE: Past intensive use of asbestos has implied severe public health
      consequences. Spatial distribution of deaths from malignant mesothelioma and of
      compensated cases for asbestos related diseases in Italy were compared to
      identify unexpected sources of asbestos exposure. METHODS: Mortality for
      malignant mesothelioma at municipal level and geographical clusters of
      compensated cases for asbestos related diseases, as proxy of industrial asbestos
      exposure, were identified in the period 1988-2001. RESULTS: Municipalities with
      at least four mesothelioma deaths and a statistically significant mortality
      excess were 148; and 53 out of them had no compensated case for asbestos-related
      diseases. Finally 22 of these lay outside of any aforementioned cluster, thus
      suggestive of a possible unrecognized exposure. CONCLUSIONS: Availability long
      term national figures and the different etiology of asbestos related diseases are
      the key features of this exercise that was applied to Italy, but can be
      replicated wherever registration systems of diseases related to long term
      exposure to asbestos are available.

PMID- 18094989
TI  - Air pollution and ED visits for asthma in Australian children: a case-crossover
      analysis.
AB  - OBJECTIVE: We aimed to determine the effects of ambient air pollutants on
      emergency department (ED) visits for asthma in children. METHODS: We obtained
      routinely collected ED visit data for asthma (ICD9 493) and air pollution
      (PM(10), PM(2.5), O(3), NO(2), CO and SO(2)) and meteorological data for
      metropolitan Sydney for 1997-2001. We used the time stratified case-crossover
      design and conditional logistic regression to model the association between air
      pollutants and ED visits for four age-groups (1-4, 5-9, 10-14 and 1-14 years).
      Estimated relative risks for asthma ED visits were calculated for an exposure
      corresponding to the inter-quartile range in pollutant level. We included same
      day average temperature, same day relative humidity, daily temperature range,
      school holidays and public holidays in all models. RESULTS: Associations between
      ambient air pollutants and ED visits for asthma in children were most consistent
      for all six air pollutants in the 1-4 years age-group, for particulates and CO in
      the 5-9 years age-group and for CO in the 10-14 years age-group. The greatest
      effects were most consistently observed for lag 0 and effects were greater in the
      warm months for particulates, O(3) and NO(2). In two pollutant models, effect
      sizes were generally smaller compared to those derived from single pollutant
      models. CONCLUSION: We observed the effects of ambient air pollutants on ED
      attendances for asthma in a city where the ambient concentrations of air
      pollutants are relatively low.

PMID- 18094990
TI  - Oral vs intravenous antibiotic prophylaxis in elective laparoscopic
      cholecystectomy: an exploratory trial.
AB  - INTRODUCTION: The application of perioperative intravenous antibiotic prophylaxis
      is often considered a necessary routine procedure. The only way to decide whether
      an antibiotic prophylaxis is necessary in elective gallbladder surgery is to
      conduct a multicenter randomized trial. The aim of this exploratory trial was to
      clarify whether an oral application of an antibiotic prophylaxis is a feasible
      and safe procedure compared to intravenous application. This exploratory trial
      was conducted prospective randomized, using a double-dummy design. The main
      target criteria included tolerance, adverse effects, pharmacokinetics, and cost
      of treatment. MATERIAL AND METHODS: Patients undergoing elective laparoscopic
      cholecystectomy were randomized double-blinded to an oral or intravenous
      application group of one antibiotic (gyrase inhibitor) using a double-dummy
      design. Exclusion criteria were acute cholecystitis, icterus, and
      choledocholithiasis. In addition to a tolerance analysis, the antibiotic
      concentration was determined in serum and bile by high-pressure liquid
      chromatography (HPLC). RESULTS: One hundred fifty one patients (75 patients with
      oral and 76 with intravenous prophylaxis) were evaluated for the tolerance
      analysis. Four patients (1 p.o., 3 i.v.) had adverse reactions to the
      antibiotics. The antibiotic serum concentration was 0.83 mg/l (p.o.) vs 8.44 mg/l
      (i.v.) before surgery, 0.81 mg/l (p.o.) vs 4.43 mg/l (i.v.) during surgery, and
      0.69 mg/l (p.o.) vs 2.77 mg/l (i.v.) after surgery. The bile concentration was
      higher after oral administration with 9.20 mg/l than after intravenous
      application with 5.79 mg/l. The costs of medication for intravenous application
      were 20 times higher than those for oral application. CONCLUSION: The oral
      application of an antibiotic (gyrase inhibitor) was feasible and safe for
      perioperative antibiotic prophylaxis in laparoscopic cholecystectomy in this
      exploratory trial.

PMID- 18094991
TI  - hPEPT1 is responsible for uptake and transport of Gly-Sar in the human bronchial
      airway epithelial cell-line Calu-3.
AB  - The purpose of this work was to investigate the apical uptake and transepithelial
      transport of Gly-Sar along with the expression of the di-/tripeptide transporters
      hPEPT1 and hPEPT2 in human Calu-3 bronchial epithelial cells. The apical Gly-Sar
      uptake rate in Calu-3 cells followed Michaelis-Menten kinetics with a Km value of
      1.3 +/- 0.3 mM and a Vmax value of 0.60 +/- 0.06 nmol cm(-2) min(-1).
      Transepithelial apical to basolateral transport of 50 microM [3H]-labelled Gly
      Sar across the Calu-3 cell monolayer was pH-dependent. The Gly-Sar flux was
      significantly reduced in the presence of delta-aminolevulinic acid (2.5 mM),
      cephalexin (25 mM), and captopril (25 mM; p < 0.05, n = 3). Reverse transcriptase
      polymerase chain reaction (RT-PCR) revealed the presence of both hPEPT1 and
      hPEPT2 mRNA in the Calu-3 cells. These findings were confirmed in healthy human
      bronchial cDNA. Restriction-endonuclease analysis identified hPEPT2 in Calu-3
      cells to be the hPEPT2*1 haplotype. Western blotting demonstrated expression of
      the hPEPT1 protein (approximately 80 kDa), and the immunolabel was mainly
      localized in the apical membrane as judged by immunolocalization studies using
      confocal laser scanning microscopy (CLSM). This work presents for the first time
      hPEPT1 and hPEPT2*1 expression in human Calu-3 cells. Surprisingly, the results
      indicate that Gly-Sar uptake and transport in Calu-3 cells are hPEPT1-mediated
      rather than hPEPT2-mediated.

PMID- 18094992
TI  - Nano-surgery at the leukocyte-endothelial docking site.
AB  - The endothelium has an important role in controlling the extravasation of
      leukocytes from blood to tissues. Endothelial permeability for leukocytes is
      influenced by transmembrane proteins that control inter-endothelial adhesion, as
      well as steps of the leukocyte transmigration process. In a cascade consisting of
      leukocyte rolling, adhesion, firm adhesion, and diapedesis, a new step was
      recently introduced, the formation of a docking structure or "transmigratory
      cup." Both terms describe a structure formed by endothelial pseudopods embracing
      the leukocyte. It has been found associated with both para- and transcellular
      diapedesis. The aim of this study was to characterize the leukocyte-endothelial
      contact area in terms of morphology and cell mechanics to investigate how the
      endothelial cytoskeleton reorganizes to engulf the leukocyte. We used atomic
      force microscopy (AFM) to selectively remove the leukocyte and then analyze the
      underlying cell at this specific spot. Firmly attached leukocytes could be
      removed by AFM nanomanipulation. In few cases, this exposed 8-12 microm wide and
      1 microm deep footprints, representing the cup-like docking structure. Some of
      them were located near endothelial cell junctions. The interaction area did not
      exhibit significant alterations neither morphologically nor mechanically as
      compared to the surrounding cell surface. In conclusion, the endothelial
      invagination is formed without a net depolymerization of f-actin, as endothelial
      softening at the site of adhesion does not seem to be involved. Moreover, there
      were no cases of phagocytotic engulfment, but instead the formation of a
      transmigratory channel could be observed.

PMID- 18094994
TI  - Characterization of leafy cotyledon1-like during embryogenesis in Theobroma cacao
      L.
AB  - Theobroma cacao L., an economically important crop for developing countries, can
      be experimentally propagated by somatic embryogenesis. Because of their potential
      roles in embryogenesis, a gene candidate strategy was initiated to find gene
      homologues of the members of the leafy cotyledon family of transcription factors.
      A homologue of the leafy cotyledon1-like gene, that encodes the HAP 3 subunit of
      the CCAAT box-binding factor, was found in the cocoa genome (TcL1L). The
      translated peptide shared a high amino acid sequence identity with the homologous
      genes of Arabidopsis thaliana, Phaseolus coccineus and Helianthus annuus. TcL1L
      transcripts mainly accumulated in young and immature zygotic embryos, and, to a
      lesser extent, in young and immature somatic embryos. In situ hybridization
      specified the localization of the transcripts as being mainly in embryonic cells
      of young embryos, the meristematic cells of the shoot and root apex of immature
      embryos, and in the protoderm and epidermis of young and immature embryos, either
      zygotic or somatic. Non-embryogenic explants did not show TcL1L expression.
      Ectopic expression of the TcL1L gene could partially rescue the Arabidopsis lec1
      mutant phenotype, suggesting a similarity of function in zygotic embryogenesis.

PMID- 18094993
TI  - Expression analyses of three members of the AtPHO1 family reveal differential
      interactions between signaling pathways involved in phosphate deficiency and the
      responses to auxin, cytokinin, and abscisic acid.
AB  - The PHO1 protein is involved in loading inorganic phosphate (Pi) to the root
      xylem. Ten genes homologous to AtPHO1 are present in the Arabidopsis thaliana
      (L.) Heyn genome. From this gene family, transcript levels of only AtPHO1,
      AtPHO1;H1 and AtPHO1;H10 were increased by Pi-deficiency. While the up-regulation
      of AtPHO1;H1 and AtPHO1;H10 by Pi deficiency followed the same rapid kinetics and
      was dependent on the PHR1 transcription factor, phosphite only strongly
      suppressed the expression of AtPHO1;H1 and had a minor effect on AtPHO1;H10.
      Addition of sucrose was found to increase transcript levels of both AtPHO1 and
      AtPHO1;H1 in Pi-sufficient or Pi-deficient plants, but to suppress AtPHO1:H10
      under the same conditions. Treatments of plants with auxin or cytokinin had
      contrasting effect depending on the gene and on the Pi status of the plants.
      Thus, while both hormones down-regulated expression of AtPHO1 independently of
      the plant Pi status, auxin and cytokinin up-regulated AtPHO1;H1 and AtPHO1;H10
      expression in Pi-sufficient plants and down-regulated expression in Pi-deficient
      plants. Treatments with abscisic acid inhibited AtPHO1 and AtPHO1;H1 expression
      in both Pi-sufficient and Pi-deficient plants, but increased AtPHO1;H10
      expression under the same conditions. The inhibition of expression by abscisic
      acid of AtPHO1 and AtPHO1;H1, and of the Pi-starvation responsive genes AtPHT1;1
      and AtIPS1, was dependant on the ABI1 type 2C protein phosphatase. These results
      reveal that various levels of cross talk between the signal transduction pathways
      to Pi, sucrose and phytohormones are involved in the regulation of expression of
      the three AtPHO1 homologues.

PMID- 18094995
TI  - Advantage of FISH analysis using FKHR probes for an adjunct to diagnosis of
      rhabdomyosarcomas.
AB  - Translocations can be detected using fluorescence in situ hybridization (FISH) in
      formalin-fixed paraffin-embedded tissues. Recently, a commercially available FKHR
      (13q14) dual-color, break-apart rearrangement probe has been developed. However,
      the advantages of using this probe have not been reported. This study
      demonstrated the usefulness of this probe for the clinical diagnosis of
      rhabdomyosarcomas (RMS). We studied 33 RMS (19 embryonal rhabdomyosarcomas
      [ERMS], including three sclerosing-type RMS, and 14 alveloar rhabdomyosarcomas
      [ARMS]). Fluorescence signals were detected for 18 of the 19 (94.7%) ERMS and 13
      of the 14 (92.8%) ARMS. A split-signal pattern was detected in 12 of 13 (92.3%)
      ARMS but was not detected in any of the ERMS, including the three sclerosing-type
      RMS. Amplification and polyploidy were present in both the ERMS and the ARMS. Our
      FISH study highlighted the excellent performance of the presently reported
      commercial break-apart probe for the detection of FKHR gene rearrangements in
      RMS. Because amplification and polyploidy were detected in both the ERMS and the
      ARMS, sufficient care should be taken when counting the nuclear signals. No
      rearrangements of the FKHR gene were found in any of the three sclerosing-type
      RMS when examined using a FISH assay, supporting the hypothesis that sclerosing
      RMS can be included as an ERMS.

PMID- 18094996
TI  - Mitochondrial expression of the two-pore domain TASK-3 channels in malignantly
      transformed and non-malignant human cells.
AB  - The presence of TASK-3 channels has been described in a number of healthy and
      malignantly transformed cells, showing mainly intracellular distribution with
      relatively insignificant labelling of the cell surface membrane. In this work,
      immunochemical and molecular biology methods were utilised to establish the
      intracellular organelle whose TASK-3 expression accounts for this strong
      intracellular labelling using cultured melanoma and HaCaT cells. Before the
      immunocytochemical experiments, the presence of TASK-3 mRNA was also confirmed in
      melanoma cells. Comparison of the results of the TASK-3- and mitochondrion
      specific labelling indicated that the TASK-3 channel subunits were strongly
      expressed by mitochondria in both investigated cell types. Moreover, prominent
      TASK-3 expression of keratinocytes could also be demonstrated in histological
      sections excised from the human skin. These results indicate that TASK-3 channels
      are present in the mitochondria in both malignantly transformed and healthy
      cells, suggesting that they might have roles in ensuring mitochondrial functions.

PMID- 18094998
TI  - Ultrastructure of Argulus japonicus Thiele, 1900 (Crustacea: Branchiura)
      collected from Guangdong, China.
AB  - Argulus japonicus Thiele, 1900 was originally described from China, but has
      spread to Europe, Africa, Australia, and North America. An ultrastructural
      description of A. japanicus has been done as one of the most common fish
      ectoparasites which has a high affect on fish life. The description was based on
      light and scanning electron microscopes studies using 13 females and 7 males
      which were collected from Shunde city in Guangdong Province, China. Typical
      Argulus body and body's appendages are associated with our specimens, carapace
      covers fourth leg, and scales separate uniformly on frontal and lateral lobes,
      ventral surface of thorax is ornamented by scales contrary of the dorsal surface
      which is quite smooth, various shapes of scales have been detected on second
      maxillae. Location and structure of copulatory accessory, number and structure of
      overlapping sclerites of sucking disk rim, melanophores patches of male, second
      swimming leg structure, and parasite's total size are the most important criteria
      which may be used to distinguish between male and female. Moreover, new
      classification criteria of Argulide, obtained by scanning electron microscopic
      study of previous species, are discussed.

PMID- 18094997
TI  - Thymoma with ganglioneuroblastomatous component: case report.
AB  - A mediastinal tumor in a 49-year-old woman with myasthenia gravis is reported.
      The tumor was well-demarcated and located in the supero-anterior mediastinum.
      Microscopically, the tumor consisted of thymic and neuroblastic tumor components,
      the latter of which consisted of immature and maturing neuronal cells, abundant
      neuropils, and Schwannian stroma. The two components intermingled with each other
      inside the tumor capsule. The tumor was diagnosed as thymoma with a
      ganglioneuroblastomatous component. The coexistence of epithelial and neuronal
      tissues in the thymic neoplasm is extremely rare.

PMID- 18094999
TI  - N-acetyl-L: -cysteine reduces the parasitism of BALB/c mice infected with
      Leishmania amazonensis.
AB  - Leishmania amazonensis infection leads to progressive diseases in a majority of
      inbred strains of mice. Glutathione (GSH) participates in a large number of
      cellular phenomena and seems to be essential for several immune functions,
      including host defense during leishmaniasis. In this study, we evaluated the
      effects of N-acetyl-L: -cysteine (NAC), as GSH supplement, on the course of L.
      amazonensis infection in susceptible BALB/c mice. The treatment with NAC (200
      mg/kg daily) was effective in raising GSH levels in both lymph node and spleen
      cells. Although this treatment did not change the footpad swelling development in
      L. amazonensis-infected mice, it caused a significant decrease in the number of
      parasites recovered from the footpad lesion and draining popliteal lymph node.
      Our data suggest that intracellular Leishmania killing in vivo was improved by
      the augment of GSH levels through NAC administration.

PMID- 18095000
TI  - Is Rhodnius nasutus (Hemiptera; Reduviidae) changing its habitat as a consequence
      of human activity?
AB  - Rhodnius nasutus, a triatomine species autochthonous in the Brazilian Northeast,
      is primarily associated with the Copernicia prunifera palm tree (Carnauba). For
      the first time, the colonization of this triatomine in another tree species is
      reported. To investigate the existence of an infected triatomine focus located in
      a periurban area of the county of Jaguaruana, Ceara, situated in the Brazilian
      Northeast, where soil is greatly altered and natural vegetation scarce, an
      entomological survey was performed. During 2 consecutive days in August 2006 and
      4 in December 2006, with the aid of live-bait traps, nine C. prunifera palms and
      seven Licania rigida trees (Oiticica), among other typical trees of the region,
      were sampled. In April 2007, 13 L. rigida trees and five C. prunifera palm trees
      were newly sampled. Considering the three investigation periods, a total of 20 R.
      nasutus specimens in C. prunifera and 52 in L. rigida were captured, in all
      developmental stages, 12.5 and 20.7%, respectively, harboring T. cruzi-like
      protozoa. The authors suggest that environmental damages are facilitating the
      ability of this species to colonize other trees besides palms.

PMID- 18095001
TI  - Spermiogenesis and chromatin condensation in the common tree shrew, Tupaia glis.
AB  - We have investigated the cellular characteristics, especially chromatin
      condensation and the basic nuclear protein profile, during spermiogenesis in the
      common tree shrew, Tupaia glis. Spermatids could be classified into Golgi phase,
      cap phase, acrosome phase, and maturation phase. During the Golgi phase,
      chromatin was composed of 10-nm and 30-nm fibers with few 50-nm to 60-nm knobby
      fibers. The latter were then transformed into 70-nm knobby fibers during the cap
      phase. In the acrosome phase, all fibers were packed into the highest-order
      knobby fibers, each about 80-100 nm in width. These chromatin fibers became
      tightly packed in the maturation phase. In a mature spermatozoon, the discoid
      shaped head was occupied by the acrosome and completely condensed chromatin. H3,
      the core histone, was detected by immunostaining in all nuclei of germ cell
      stages, except in spermatid steps 15-16 and spermatozoa. Protamine, the basic
      nuclear protein causing the tight packing of sperm chromatin, was detected by
      immunofluorescence in the nuclei of spermatids at steps 12-16 and spermatozoa.
      Cross-immunoreactivity of T. glis H3 and protamine to those of primates suggests
      the evolutionary resemblance of these nuclear basic proteins in primate germ
      cells.

PMID- 18095002
TI  - Effects of neuropeptide F on regeneration in Girardia tigrina (Platyhelminthes).
AB  - The effects of neuropeptide F (NPF; from Moniezia expansa) on the regeneration of
      Girardia tigrina were studied. The animals were decapitated and incubated in
      water (control) or NPF. The dynamics of the proliferation of the neoblasts in the
      developing tissue were studied during the course of regeneration by monitoring
      the mitotic index (MI). The effects of incubation in FMRFamide and GYIRFamide on
      the MI were also tested. The course of cephalic regeneration was followed with in
      vivo computer-assisted morphometry for up to 7 days. The development of the
      regenerating nervous system and the musculature was visualised by immunostaining
      with a primary antiserum to the C-terminal decapeptide of NPF (YFAIIGRPRFa) and
      tetramethylrhodamine-isothiocyanate-conjugated phalloidin, which stains F-actin
      in muscle filaments. The study showed that NPF had a stimulatory effect on the
      mitotic activity of the neoblasts. FMRFamide and GYIRFamide did not have this
      effect. NPF also stimulated the growth of the regenerating head and the growing
      nervous system and musculature. NPF is postulated to have a morphogenetic action
      in the regenerating animals.

PMID- 18095003
TI  - Chemical differences between seeds and elaiosomes indicate an adaptation to
      nutritional needs of ants.
AB  - Ant-dispersed plants usually produce seeds with appendages (elaiosomes) as reward
      for ants. Plants that produce high-quality elaiosomes benefit because ants
      preferentially disperse their diaspores. We therefore hypothesized that seeds and
      elaiosomes differ in chemical composition in ways that make elaiosomes of high
      nutritional quality for ants, capable of providing essential dietary components
      that explain the increased fitness and higher gyne production documented for
      colonies with elaiosome consumption. To test the hypothesis we analysed the
      content and composition of lipids, amino acids, soluble carbohydrates, proteins
      and starch in seeds and elaiosomes of 15 central European ant-dispersed plants.
      After separating the different fractions, total lipids were determined
      gravimetrically, fatty acids and soluble carbohydrates were detected by gas
      chromatography (GC) and GC-mass spectrometry, free amino acids by an amino acid
      analyser while starch and protein were analysed photometrically. Seeds
      accumulated high molecular weight compounds such as proteins and starch, whereas
      elaiosomes accumulated more easily digestible low molecular weight compounds such
      as amino acids and monosaccharides. Analysis of similarities and similarity
      percentages analysis demonstrated that the composition of fatty acids, free amino
      acids and carbohydrates differed markedly between elaiosomes and seeds. The most
      important difference was in total amino acid content, which was on average 7.5
      times higher in elaiosomes than in seeds. The difference was especially marked
      for the nitrogen-rich amino acid histidine. The availability of essential
      nutrients and, in some species, the higher nitrogen content in elaiosomes suggest
      that their nutritional value for larvae plays a key role in this interaction.

PMID- 18095004
TI  - The neurogenic bladder: medical treatment.
AB  - Neurogenic bladder sphincter dysfunction (NBSD) can cause severe and irreversible
      renal damage and bladder-wall destruction years before incontinence becomes an
      issue. Therefore, the first step in adequate management is to recognize early the
      bladder at risk for upper- and lower-tract deterioration and to start adequate
      medical treatment proactively. Clean intermittent catheterization combined with
      anticholinergics (oral or intravesical) is the standard therapy for NBSD. Early
      institution of such treatment can prevent both renal damage and secondary bladder
      wall changes, thereby potentially improving long-term outcomes. In children with
      severe side effects or with insufficient suppression of detrusor overactivity
      despite maximal dosage of oral oxybutynin, intravesical instillation is an
      effective alternative. Intravesical instillation eliminates systemic side effects
      by reducing the first-pass metabolism and, compared with oral oxybutynin,
      intravesical oxybutynin is a more potent and long-acting detrusor suppressor.
      There is growing evidence that with early adequate treatment, kidneys are saved
      and normal bladder growth can be achieved in children so they will no longer need
      surgical bladder augmentation to achieve safe urinary continence in adolescence
      and adulthood.

PMID- 18095005
TI  - Expression of mRNA for functional molecules in urinary sediment in
      glomerulonephritis.
AB  - Recent studies have suggested that gene expression studies using urinary sediment
      might be a non-invasive approach to assessing activity and pathogenesis in
      glomerulonephritis. However, little information is available regarding the mRNA
      expression patterns of functional molecules, such as T-bet, GATA-3, FOXP3, and
      retinoic acid-inducible gene-I (RIG-I), in urinary sediment, from patients with
      immunocomplex-mediated glomerulonephritis. Fourteen lupus nephritis (LN)
      patients, 13 IgA nephropathy (IgAN) patients, and 12 healthy controls were
      enrolled in the study. The mRNA expressions of T-bet, GATA-3, FOXP3 and RIG-I in
      urinary sediment were measured using real time quantitative polymerase chain
      reaction. We also studied the expression of RIG-I in kidney tissue specimens
      obtained from LN and IgAN patients. Significant differences in the expression
      patterns of GATA-3, FOXP3 and RIG-I, and marginal differences in T-bet
      expression, were observed between the three study groups. Immunofluorescent
      staining for RIG-I was observed in the tissue specimens from the LN patients, but
      not in those from the IgAN patients. The mRNA expression patterns of T-bet, GATA
      3, FOXP3 and RIG-I in urinary sediment differ according to diagnostic category.
      These results suggest that the measurement of these target gene expressions might
      be a useful, non-invasive method for clinical monitoring and studying of
      pathogenesis in glomerulonephritis.

PMID- 18095006
TI  - Recurrent chyloperitoneum: a rare complication of peritoneal dialysis.
AB  - We report the spontaneous development of recurrent chyloperitoneum as a
      complication of peritoneal dialysis in a toddler. An 18-month-old boy with end
      stage renal disease (ESRD) on continuous cycling peritoneal dialysis developed
      spontaneous chyloperitoneum. He was treated conservatively, with a low-fat diet
      supplemented with medium-chain triglycerides. The chyloperitoneum resolved within
      2 days of his being on the low-fat diet, but it recurred after re-institution of
      regular feeds on four occasions. After 3 months, the chyle leak finally resolved
      after an extended period of low-fat feeds. Chyloperitoneum is a rare complication
      of peritoneal dialysis that can be confused with signs of peritonitis, and it is
      important to differentiate between the two so that appropriate management can be
      undertaken. This paper discusses the possible causes, management and
      complications of recurrent chyloperitoneum.

PMID- 18095007
TI  - Copenhagen--a significant source of birch (Betula) pollen?
AB  - Current aerobiological research applies the hypothesis that the main source of
      atmospheric birch (Betula) pollen is forest trees. Our results indicate that the
      measured levels in Copenhagen are not only due to birch trees in Danish forests
      but that the urban areas also seem to be a significant source of birch pollen. A
      number of episodes in 2003 with enhanced pollen levels in Copenhagen seem to be
      associated with parks and gardens inside and just outside the city. Our results
      also indicate one long-range transport episode from remote sources in Poland and
      Germany. Finally, our results show that the pollen levels vary considerably over
      the day and geographically between Copenhagen and the city of Roskilde, 40 km
      away. We suggest, that these differences in time and space in the pollen levels
      are mapped using an integrated monitoring strategy.

PMID- 18095008
TI  - Less nausea, emesis, and constipation comparing hydromorphone and morphine? A
      prospective open-labeled investigation on cancer pain.
AB  - GOALS OF WORK: The purpose of this trial was to evaluate the effect of long-term
      treatment with either oral sustained-release hydromorphone (HM) or morphine (M)
      on nausea, emesis, and constipation. MATERIALS AND METHODS: In a prospective,
      open-labeled, controlled trial, 100 outpatients with cancer pain and treatment
      with HM or M were enrolled. Mobility, pain, and gastrointestinal symptoms were
      assessed by the ECOG performance status, selected items of the EORTC
      questionnaire and Numerical Rating Scales (NRS). Data were analyzed using
      descriptive and confirmatory statistics (paired t-test, chi square test, Poisson
      regression). MAIN RESULTS: Demographic and medical data were comparable in both
      treatment groups. Taking into account different conversion factors, opioid doses
      (M 94.4 mg/d vs. HM 137.6 [HM/M = 1:5], p = 0.05 and HM 206.4 [HM/M = 1:7.5], p =
      0.0002, respectively) were higher under hydromorphone and NRS of pain (M 2.3 vs.
      HM 3.6, p = 0.0002) lower under morphine. Nausea and emesis did not attenuate in
      33% of patients. NRS of nausea (M 2.5 vs. HM 1.5; p = 0.01), incidences of emesis
      (M 0.7/d vs. HM 0.1/d, p = 0.0001), the consumption of antiemetics (M 26 vs. HM
      14, p = 0.01), and the number of constipated patients (M 8 vs. HM 2, p = 0.04)
      were higher in the morphine group. An extended use of substances for symptom
      control revealed constipating effects (M 31 vs. HM 13, p = 0.0003) and was
      associated with a higher incidence of constipation in the morphine group.
      CONCLUSIONS: Symptom control in outpatients with cancer pain may be complicated
      by a symptom controlling medication. Particularly, antiemetics revealed
      potentially constipating effects. Despite lower opioid doses, morphine provided a
      better pain control but produced more side effects. Comparing hydromorphone with
      morphine, it remains unclear if fewer incidences of constipation and nausea in
      the hydromorphone group were related to pharmacodynamic effects or to a less
      effective pain control with significantly higher NRS for pain. However, the
      conversion factor of oral hydromorphone and morphine needs to be questioned.

PMID- 18095009
TI  - Strong slime production is a marker of clinical significance in Staphylococcus
      epidermidis isolated from intravascular catheters.
AB  - Biofilm production was assessed in 52 Staphylococcus epidermidis isolates from
      the catheters of 52 patients with catheter-related bloodstream infections (CR
      BSI) and compared with 14 isolates from the skin of healthy volunteers by
      spectrophotometry. The isolates were classified as non- (G1), weak- (G2) or
      strong- (G3) slime producers based on optical density, and as producers and non
      producers based on the results of the Congo red agar test. Differences (p =
      0.012) in the proportion of G1, G2 and G3 among the isolates were found between
      catheter and healthy skin strains: there was a higher percentage of G1 types
      among the healthy skin strains (35.7 vs. 11.5%; p = 0.046) and a higher
      percentage of G3 types among the catheter isolates (44.2 vs. 0%; p = 0.001). No
      significant differences were found with the Congo red agar test. G3 is a
      phenotypic marker for CR-BSI.

PMID- 18095010
TI  - Iatrogenic splenic injury in postoperative patients: a series of case reports.
AB  - The purpose of this study was to report case studies of iatrogenic splenic
      injuries on computed tomography (CT) in symptomatic postsurgical patients. The
      medical records and CT studies of all patients with injury to the spleen after
      abdominal surgery were reviewed. CT was performed in the postoperative period,
      urgently in all patients. Unsuspected splenic injuries were found on CT performed
      in the early postoperative period in seven symptomatic patients (five women and
      two men, age range 21-81 years) after various abdominal surgical procedures.
      Injuries as detected on CT included splenic infarct in five, subcapsular hematoma
      in two, and laceration of the spleen in one. These findings were the only
      abnormal abdominal findings in four of the patients and were probably the source
      of the postoperative abdominal pain and fever. Splenic injury is a rare
      complication of abdominal surgery. It is often the radiologist who diagnoses the
      injury, and awareness of this possible complication can obviate further
      investigations.

PMID- 18095011
TI  - Activation of two forms of locomotion by a previously identified trigger
      interneuron for swimming in the medicinal leech.
AB  - Higher-order projection interneurons that function in more than one behavior have
      been identified in a number of preparations. In this study, we document that
      stimulation of cell Tr1, a previously identified trigger interneuron for swimming
      in the medicinal leech, can also elicit the motor program for crawling in
      isolated nerve cords. We also show that motor choice is independent of the firing
      frequency of Tr1 and amount of spiking activity recorded extracellularly at three
      locations along the ventral nerve cord prior to Tr1 stimulation. On the other
      hand, during Tr1 stimulation there is a significant difference in the amount of
      activity elicited in the ventral nerve cord that correlates with the motor
      program activated. On average, Tr1 stimulation trials that lead to crawling
      elicit greater amounts of activity than in trials that lead to swimming.

PMID- 18095012
TI  - 1H NMR-based metabolomic identification of at-risk areas after myocardial
      infarction in swine.
AB  - OBJECT: (1)H NMR-based metabolic profiling has been used to investigate areas of
      the heart after an acute myocardial infarction. METHODS: Tissue was obtained from
      control, at-risk (areas that survive within the infarct zone) and necrotic
      myocardium after 48 min of left anterior descending coronary artery occlusion and
      2 h of reperfusion in a swine model. HR-MAS (high resolution magic angle
      spectroscopy) spectra from intact tissue and tissue extract spectra were obtained
      for each region and statistical models were built for each type of spectra
      allowing differentiation between control, at-risk and necrotic heart. RESULTS: At
      risk and, especially, necrotic areas have a reduced concentration of NMR visible
      metabolites as compared to control tissue, total creatine (phosphorilated and
      unphosphorilated) being the single most important metabolite in the different
      discriminant models. Creatine concentration decreased from 18.28 +/- 0.84
      micromols/g fresh weight in controls to 12.58 +/- 2.89 (P < 0.05) and 9.96 +/-
      2.21 (P < 0.01) in at-risk and necrotic areas, respectively. Taurine and myo
      inositol were also involved in the discriminant models. HR-MAS spectra also
      showed an increase in lipid signals at 0.9 and 1.28 ppm as markers of necrotic
      tissue. These results support the view that the analysis of in vivo (1)H MRS may
      have value in differentiating normal, at-risk and infarcted myocardium.

PMID- 18095013
TI  - Elderly onset systemic lupus erythematosus (SLE) presenting with disseminated
      intravascular coagulation (DIC).
AB  - We describe an unusual case of elderly onset systemic lupus erythematosus (SLE)
      that presented with disseminated intravascular coagulation (DIC). An 86-year-old
      man who complained of general malaise was admitted for evaluation and treatment
      of thrombocytopenia. He was diagnosed as having SLE and DIC based on the criteria
      of the American College of Rheumatology for SLE (renal involvement, hematological
      abnormalities, and positivity for antinuclear antibody and lupus anticoagulant)
      and the criteria for DIC presented by the subcommittee on DIC of the ISTH (a
      large increase of fibrin degradation products [3 points] and a platelet count <50
      x 10(3)/ml [2 points], resulting in a score of 5; a score > or =5 is compatible
      with DIC). The patient was treated with corticosteroid therapy (30 mg/day); the
      DIC and SLE remitted, and his renal function improved, but he developed pulmonary
      tuberculosis. Timely diagnosis, appropriate treatment, and an awareness of the
      potential for serious infections are of utmost importance when dealing with
      patients with elderly onset SLE.

PMID- 18095014
TI  - Manganese superoxide dismutase Ala-9Val mitochondrial targeting sequence
      polymorphism in systemic lupus erythematosus in Poland.
AB  - Systemic lupus erythematosus (SLE) is a chronic and progressive autoimmune
      disease in which reactive oxygen species contribute to pathogenesis. We analysed
      the distribution of manganese superoxide dismutase (MnSOD2) 47C>T (Ala-9Val)
      functional polymorphic variants within the mitochondrial targeting sequence in
      SLE patients (n = 102) and controls (n = 199). We did not find significant
      differences in the distribution of MnSOD2 47C>T polymorphic variants in SLE
      patients and controls. However, we found that MnSOD2 Val/Val genotype (recessive
      model) showed a significant association with Raynaud's phenomenon, odds ratio
      (OR) = 12.000 [95% confidence interval (CI) = 2.315-62.193], p = 0.0015. We also
      found that the MnSOD2 Val/Val genotype contributes to immunologic manifestations,
      OR = 2.957 (95% CI = 1.207-7.243), p = 0.0222, and anti-dsDNA antibody presence
      OR = 3.365 (95% CI = 1.364-8.304), p = 0.0107, in patients. Our observations
      indicate that MnSOD2 Val/Val variant can be linked to some clinical
      manifestations in patients with SLE.

PMID- 18095015
TI  - Acute hepatitis in adult Still's disease during corticosteroid treatment
      successfully treated with anakinra.
AB  - Adult onset Still's disease (AOSD) is a well-recognized clinical disorder
      characterized by involvement of various organs, including liver. However, acute
      hepatitis or hepatic failure is extremely rare, and most of the reported cases
      occurred during treatment with hepatotoxic drugs. Anakinra is an interleukin-1
      receptor antagonist (IL-1Ra). Experimental and clinical data support a central
      role for IL-1Ra in fulminant hepatic failure. We report the case of a patient
      with AOSD complicated with acute hepatitis during treatment with corticosteroids,
      which was dramatically improved with anakinra.

PMID- 18095016
TI  - Fungal diversity of Norway spruce litter: effects of site conditions and
      premature leaf fall caused by bark beetle outbreak.
AB  - Fungi play an important role in leaf litter decomposition due to their ability to
      break down the lignocellulose matrix, which other organisms are unable to digest.
      However, little is known regarding the factors affecting components of fungal
      diversity. Here, we quantified richness of internal fungi in relation to litter
      nutrient and phenolic concentrations, sampling season (spring or fall), and
      premature leaf shedding due to low precipitation and infestation of bark beetles
      (mainly Ips typographus and Ips duplicatus). The study was conducted in 37-year
      old Norway spruce [Picea abies (L.) Karst.] stands, with three plots each in
      mixed forest (MF) and coniferous forest (CF) site conditions in south-central
      Poland. Fifty-four species of sporulating fungi were identified in 2,330 freshly
      fallen needles sampled during 2003-2005, including 45 species in MF and 31 in CF.
      The significantly higher number of species in MF was likely related to moister
      conditions at that site. Among isolated fungi, 22% (12 species) were identified
      as endophytes of Norway spruce in prior studies. During spring of 2005, we found
      less than half the number of isolates and fungal species at each forest site as
      compared to fall for the two prior years. This pattern was observed in typical
      soil fungi (e.g., Penicillium daleae, Penicillium purpurogenum) and
      endophytes/epiphytes (e.g., Aureobasidium pullulans, Alternaria alternata,
      Cladosporium spp., and Lophodermium piceae). Premature shedding of needles was
      the most likely cause of this decline because it shortened the time period for
      fungi to infect green needles while on the tree. For all sites and sampling
      periods, richness of internal fungi was strongly and positively related to the
      age of freshly fallen litter (assessed using needle Ca concentration as a needle
      age tracer) and was also negatively related to litter phenolic concentration.
      Richness of internal fungi in freshly fallen litter may be adversely affected by
      low soil moisture status, natural inhibitors slowing fungal colonization (e.g.,
      phenolics) and biotic (e.g., insect infestation) and abiotic (e.g., drought)
      factors that shorten leaf life span.

PMID- 18095017
TI  - Clarification of the figure-of-eight suture technique.

PMID- 18095018
TI  - A proposed anatomical typing of the right internal spermatic vein: importance for
      percutaneous sclerotherapy of varicocele.

PMID- 18095019
TI  - Restenosis of the CYPHER-Select, TAXUS-Express, and Polyzene-F nanocoated cobalt
      chromium stents in the minipig coronary artery model.
AB  - PURPOSE: To date no direct experimental comparison between the CYPHER-Select and
      TAXUS-Express stents is available. Therefore, we investigated late in-stent
      stenosis, thrombogenicity, and inflammation, comparing the CYPHER-Select, TAXUS
      Express, and custom-made cobalt chromium Polyzene-F nanocoated stents (CCPS) in
      the minipig coronary artery model. METHODS: The three stent types were implanted
      in the right coronary artery of 30 minipigs. The primary endpoint was in-stent
      stenosis assessed by quantitative angiography and microscopy. Secondary endpoints
      were inflammation and thrombogenicity evaluated by scores for inflammation and
      immunoreactivity (C-reactive protein and transforming growth factor beta). Follow
      up was at 4 and 12 weeks. RESULTS: Stent placement was successful in all animals;
      no thrombus deposition occurred. Quantitative angiography did not depict
      statistically significant differences between the three stent types after 4 and
      12 weeks. Quantitative microscopy at 4 weeks showed a statistically significant
      thicker neointima (p = 0.0431) for the CYPHER (105.034 +/- 62.52 microm) versus
      the TAXUS (74.864 +/- 66.03 microm) and versus the CCPS (63.542 +/- 39.57
      microm). At 12 weeks there were no statistically significant differences.
      Inflammation scores at 4 weeks were significantly lower for the CCPS and CYPHER
      compared with the TAXUS stent (p = 0.0431). After 12 weeks statistical
      significance was only found for the CYPHER versus the TAXUS stent (p = 0.0431).
      The semiquantitative immunoreactivity scores for C-reactive protein and
      transforming growth factor beta showed no statistically significant differences
      between the three stent types after 4 and 12 weeks. CONCLUSIONS: The CCPS
      provided effective control of late in-stent stenosis and thrombogenicity in this
      porcine model compared with the two drug-eluting stents. Its low inflammation
      score underscores its noninflammatory potential and might explain its equivalence
      to the two DES.

PMID- 18095020
TI  - The carbon footprint of laparoscopic surgery: should we offset?
AB  - The aim of this study was to estimate the effect that the expansion of
      laparoscopic surgery has had on global warming. Laparoscopic procedures performed
      in a hospital over a 10-year period were analysed. The number of CO(2) cylinders
      (size C) used over a 2.5-year period and the "carbon footprint" of each cylinder
      was calculated. There was a fourfold increase of in the number of laparoscopic
      procedures performed over the past 10 years (n = 174-688). Median operative time
      for the laparoscopic procedures performed over the past 2.5-years (n = 1629) was
      1.01 h (range 0.3-4.45 h) with 415 cylinders used in this period giving an
      operative time per cylinder of 3.96 h. Each cylinder produces only 0.0009 of
      tonnes of CO(2). Despite increasing frequency of the laparoscopic approach in
      general surgery, its impact on global warming is negligible.

PMID- 18095021
TI  - Complications after transanal endoscopic microsurgical resection correlate with
      location of rectal neoplasms.
AB  - PURPOSE: Transanal endoscopic microsurgery (TEM) is a technique that has found
      its place in routine practice due to its minimal invasive character and
      associated low morbidity. The purpose of this study was to assess the influence
      of anatomical variables of rectal neoplasms as well as surgeon experience on
      postoperative complications in patients undergoing TEM at a tertiary care center.
      METHODS: Data from 288 patients undergoing TEM over a 16 year period were entered
      in a prospective data base. Anatomical data of rectal neoplasms, operative data,
      and early postoperative outcome were analyzed retrospectively. RESULTS: Overall
      surgical complications [OR 7.0 (1.5-45,5); p < 0.01] and bleeding [OR 222 (82 -
      14316); p < 0.01] correlated with the localization of the neoplasm on the lateral
      wall of the rectum. Furthermore there was a trend for more surgical overall
      complications as well as bleeding in neoplasms with a diameter of >2 cm and
      neoplasms located >8 cm from the anal verge. Complications did not correlate with
      the number of TEM procedures performed. CONCLUSION: TEM resection of neoplasms
      located on the lateral rectal wall have a higher risk of bleeding. The learning
      curve for transanal endoscopic microsurgery appears to be negligible in surgeons
      with experience in minimal invasive surgery.

PMID- 18095022
TI  - Randomized clinical trial comparing oral prednisone (50 mg) with placebo before
      laparoscopic cholecystectomy.
AB  - BACKGROUND: Intravenous administration of dexamethasone 90 min before
      laparoscopic cholecystectomy improves surgical outcome but may be impractical.
      The objective of this study was to assess the clinical efficacy of oral self
      administration of prednisone 2 h before ambulatory laparoscopic cholecystectomy.
      METHODS: In a double-blind placebo-controlled study, 200 patients were randomized
      to oral administration of prednisone (50 mg) or placebo 2 h before laparoscopic
      cholecystectomy. Patients received a similar standardized anaesthetic, surgical,
      and analgesic treatment. The primary outcome was pain 24 h after surgery and
      secondary outcomes were fatigue and malaise 24 h after surgery. Outcome
      parameters were registered before operation, on the day of operation, and the
      following two days. Analgesic and antiemetic requirements were registered, and
      nausea and vomiting were assessed twice within the first 24 h. Side-effects and
      30-day follow-up for morbidity were registered. RESULTS: Data from 184 patients
      were available for statistical analysis. There were no significant differences in
      side-effects or complications between the surgical groups (P > 0.05). No
      significant intergroup differences in 24-h pain, fatigue or malaise scores or any
      other variables were found (P > 0.05). CONCLUSION: There is no important clinical
      gain of preoperative oral steroid administration compared with placebo in
      patients undergoing laparoscopic cholecystectomy.

PMID- 18095023
TI  - Severe and fatal complications after ERCP: analysis of 2555 procedures in a
      single experienced center.
AB  - BACKGROUND AND STUDY AIMS: The majority of recent large series on endoscopic
      retrograde cholangiopancreatography (ERCP) complications have been multicenter
      studies reflecting varying degrees of experience and ERCP volume; major ERCP
      complications are associated with low case volume. The aim of this study was to
      report and analyze the frequency of severe and fatal complications associated
      with ERCP at a single specialized surgical high-volume referral center (Turku
      University Central Hospital). METHODS: All scheduled ERCP procedures (n = 2788)
      at our unit between January 1997 and December 2005 were included and the
      procedure-related severe and fatal complications were assessed by retrospective
      chart review. Complications were classified as severe or fatal according to
      standardized guidelines. RESULTS: The number of ERCP procedures performed was
      2555, of which 71% were therapeutic and 29% were diagnostic. Seventeen (0.8%)
      severe complications were identified in 16 patients, of whom 15 underwent a
      therapeutic endoscopic procedure. Of the 17 severe complications, perforation
      constituted five cases (0.2%), pancreatitis occurred in five patients (0.2%),
      bleeding in five cases (0.2%), and two patients suffered from purulent
      cholangitis (0.1%). Procedure-related mortality was 0.08% (n = 3). CONCLUSIONS:
      In our study the rate of severe or fatal complications of ERCP is low in
      experienced hands at a high-volume center, comparing favorably to corresponding
      complication rates of multicenter series, which further supports the importance
      of centralizing ERCP procedures in high-volume advanced centers.

PMID- 18095024
TI  - Endoscopic vacuum-assisted closure of anastomotic leakage following anterior
      resection of the rectum: a new method.
AB  - BACKGROUND: Conservative treatment of anastomotic leakage after anterior
      resection of the rectum seems to be possible in patients who have no occurrence
      of generalized peritonitis. This report describes a new method of endoscopic
      management of large anastomotic leakage in these patients. METHOD: The main
      feature of this new method is the endoscopically assisted placement of an open
      cell sponge connected to a vacuum device into the abscess cavity via an
      introducer device. The sponge system is changed every 48-72 h. RESULTS: Twenty
      nine patients with an anastomotic leakage after anterior resection were treated
      with the endoscopic vacuum therapy. The total duration of endovac therapy was
      34.4 +/- 19.4 days. The total number of endoscopic sessions per patient was 11.4
      +/- 6.3. In 21 of the 29 patients, a protecting stoma was created at the primary
      operation. Four patients were treated successfully without the need of a
      secondary stoma. Definitive healing was achieved in 28 of the 29 patients.
      CONCLUSIONS: Endoscopic vacuum-assisted closure is a new efficacious modality for
      treating anastomotic leakage following anterior resection due to an effective
      control of the septic focus. Further studies will show if it is possible to
      reduce the high mortality rate of patients with anastomotic leakage through the
      avoidance of surgical reinterventions while at the same time preserving the
      sphincter function.

PMID- 18095025
TI  - Laparoscopic antireflux surgery in the elderly.
AB  - BACKGROUND: Both gastroesophageal reflux and paraesophageal hernias are more
      common in the elderly, but often these patients are not referred for surgery
      because of their age. In this study we determined the outcome for laparoscopic
      antireflux surgery in patients aged 70 years or older, in whom either symptoms of
      gastroesophageal reflux or a large paraesophageal hernia was the indication for
      surgery. METHOD: From a prospectively maintained clinical database of patients
      undergoing laparoscopic antireflux surgery, all patients aged 70 years or older
      were identified and their outcome was determined. RESULTS: Two hundred ten
      patients were identified. In 129 a large paraesophageal hiatus hernia was the
      primary indication for surgery, and in 81 patients the indication was reflux.
      Mean operation time was significantly longer in patients undergoing surgery for a
      large hiatus hernia (109 vs. 72 min), and conversion to open surgery was required
      more often (11.6% vs. 4.4%), compared to patients with reflux alone. Follow-up
      information was available for 95% of patients. Postoperative symptom scores for
      heartburn and dysphagia improved significantly and patients' satisfaction with
      surgery was high. CONCLUSION: Laparoscopic antireflux surgery in patients aged 70
      years or older has a satisfactory clinical outcome. Elderly patients should not
      be refused laparoscopic antireflux surgery only because of their age.

PMID- 18095026
TI  - A novel method for artery detection in laparoscopic surgery.
AB  - BACKGROUND: One of the most important difficulties in laparoscopic surgery is
      intraoperative blood vessel detection. An accidental injury to a blood vessel may
      cause serious complications and could result in changing from a laparoscopic
      procedure to open surgery. Moreover, differentiating arteries from veins is
      necessary in all surgical cases. In this study we evaluate a new image-processing
      method for artery detection that would be useful during laparoscopic and
      endoscopic procedures. It is possible to install the program on any ordinary
      laparoscopy set and it displays the artery's region on the monitor. METHODS: This
      method uses the artery's pulse to detect an artery and distinguish it from veins.
      By subtracting the systolic and diastolic images, the change regions are detected
      and shown on a monitor. The performance of this method in detecting arteries in
      simulation and in real laparoscopic surgery is evaluated. Artery detection in
      different pulse rates, different artery depths, and different blood pressures is
      tested via the simulation phase. It is also tested in two laparoscopic surgeries,
      one on a kidney and one on a stomach. RESULTS: In simulation phase the method can
      correctly detect all arteries that are not too deep and can move superficial
      tissues with zero false-negative and false-positive rates. In real laparoscopy,
      the false-positive rate was 8% and the false-negative rate was 5%. CONCLUSION:
      This method is a noninvasive, reliable, and cost-effective technique to detect
      artery regions, even if some of them are covered with fat or other tissues, while
      suppressing veins and other tissues.

PMID- 18095027
TI  - Patterns of esophageal acid exposure after laparoscopic Heller's myotomy and
      Dor's fundoplication for esophageal achalasia.
AB  - BACKGROUND: Heller's myotomy for esophageal achalasia is associated with less
      esophageal acid gastroesophageal reflux when combined a Dor's fundoplication. The
      Aim of the study was to assess the incidence of postoperative esophageal acid
      exposure after laparoscopic Heller's myotomy and Dor's fundoplication (HM-DF).
      METHODS: Seventy six patients (37 males) with esophageal achalasia were
      prospectively followed-up by clinical interview and laboratory tests before and
      after laparoscopic HM-DF. A symptom score was used for clinical assessment.
      Laboratory assessment included esophageal standard manometry, esophagogram and
      esophageal pH 24-hour monitoring before and 1- and 5-years after surgery.
      RESULTS: Symptom score improved at 1-year after surgery (P < 0.001). Heartburn
      was only reported by 5 patients, dysphagia or/and regurgitation by 28 and
      substernal pain by 12. 91% of patients had satisfactory functional results.
      Pathological esophageal exposure to acid was seen in 21% of the cases.
      Pathological acid events showed the features of pseudoreflux in 66%t and those of
      true GER in 34%. Pathologically increased esophageal exposure to acid was more
      commonly detected in patients with a pseudodiverticulum (P = 0.001) and was
      related to the diameter of distal esophagus and symptom score (P < 0.001). There
      was no reduction in esophageal acid exposure after treatment with proton pump
      inhibitors in 16 patients. Neither the symptom score nor esophageal acid exposure
      at esophageal pH monitoring changed significantly at the 5-year follow-up in 35
      patients. Esophageal configuration remained unchanged. CONCLUSIONS: Increased
      esophageal exposure to acid after laparoscopic HM-DF for esophageal achalasia i)
      is detected in 21% of patients, and is rather the result of food stagnation than
      of true GER, ii) is more commonly seen in cases with pseudodiverticulum, iii) is
      related to the diameter of distal esophagus, iv) does not respond to
      antisecretory treatment and v) does not deteriorate by time.

PMID- 18095028
TI  - Topical sucralfate decreases pain after hemorrhoidectomy and improves healing: a
      randomized, blinded, controlled study.
AB  - PURPOSE: Oral and topical sucralfate is regularly used in ulcers of
      gastrointestinal tract, vaginal and perianal excoriations, and radiation burns.
      This study was designed to determine whether there was any advantage of topical
      application of sucralfate in reducing postoperative pain and promoting wound
      healing after open hemorrhoidectomy in patients with Grades III or IV
      hemorrhoids. METHODS: A total of 116 patients were randomly assigned to receive
      sucralfate cream (sucralfate group) or placebo cream (control group) applied to
      the surgical site. Weekly pain score was evaluated by using Visual Analog Scale.
      The amount of analgesic tablets consumed in each week also was assessed. At the
      end of four weeks, two independent surgeons assessed the wound healing. RESULTS:
      There was no significant difference in age, gender distribution, and number of
      excised hemorrhoid piles between the two groups. Patients in the topical
      sucralfate group experienced significantly less pain at Day 7 (Visual Analog
      Scale +/- standard error of the mean, 3.7+/-0.3 vs. 6.1+/-0.7; P<0.002) and at
      Day 14 (1.6+/-0.2 vs. 3.1+/-0.6; P<0.01). Likewise patients who received
      sucralfate cream used less analgesic tablets compared with the placebo group. In
      the sucralfate group, the overall wound healing ranked significantly better than
      in controls (P<0.02). CONCLUSIONS: Topical sucralfate significantly reduces pain
      at Days 7 and 14 after hemorrhoidectomy and promotes faster wound healing
      compared with that of a placebo.

PMID- 18095029
TI  - Color Doppler imaging predicts portal invasion by pancreatic adenocarcinoma.
AB  - BACKGROUND: Tumor infiltration of the intima of the portal vein (PV) and superior
      mesenteric vein (SMV) by pancreatic adenocarcinoma is classically considered a
      criterion for unsuitability for resection and poor prognosis. This study was
      performed to evaluate modern color duplex imaging (CDI) for the assessment of
      PV/SMV infiltration by pancreatic adenocarcinomas. METHOD: From 1994 to 2005,
      Whipple's procedure or pylorus-preserving pancreato-duodenectomy (PPPD) was
      performed in 303 patients with pancreatic adenocarcinoma; 35 of these underwent
      partial PV/SMV resection. Applying a previously reported CDI score, we evaluated
      the integrity of the echogenic border layer between the vein and tumor (mural
      demarcation) and maximum blood flow velocity (V (max)) in the PV segment in
      contact with the tumor. The results were compared to the final histological
      findings in the resected venous walls. RESULTS: CDI findings correlated well with
      the histological invasion grades. By measuring V (max )and evaluating mural
      demarcation, we observed a sensitivity of 66.7% and 100% and a specificity of
      98.3% and 93.9%, respectively, in predicting full thickness vein invasion,
      including the intima. V (max) above 80 cm/s and lack of mural demarcation were
      predictors of PV/SMV invasion. The postoperative survival rates depended on the
      depth of tumor infiltration into the PV/SMV. CONCLUSIONS: Modern CDI is a
      reliable and valid technique for evaluation of morphological and hemodynamic
      parameters in the portal vein segment adjacent to pancreatic adenocarcinoma.
      Maximal blood-flow velocity in the portal segment in contact with the tumor and
      absence of the echogenic vessel-parenchymal sonographic interface are parameters
      predictive of tumor infiltration of the portal intima.

PMID- 18095030
TI  - Incomplete ablation after radiofrequency ablation of hepatocellular carcinoma:
      analysis of risk factors and prognostic factors.
AB  - BACKGROUND: Complete ablation rates after a single session of radiofrequency
      ablation (RFA) of hepatocellular carcinoma (HCC) vary from 48% to 97%. Limited
      data are available regarding risk factors and prognostic significance of
      incomplete ablation. METHODS: Between April 2001 and March 2006, 298 patients
      underwent RFA of 393 HCC nodules with an intent of complete ablation after a
      single session. Risk factors for incomplete ablation and its effect on overall
      survival were analyzed. RESULTS: Two hundred seventy-three (91.6%) underwent
      complete tumor ablation, whereas the other 25 (8.4%) underwent incomplete tumor
      ablation after a single session of RFA. By multivariate analysis, tumor size > 3
      cm (P = .049) was found to be the only independent risk factor for incomplete
      ablation. There was no statistically significant difference in overall survival
      between patients with complete and incomplete ablation. By univariate analysis,
      no previous transarterial chemoembolization (TACE), preoperative serum alfa
      fetoprotein < or = 100 microg/mL, and complete response after further treatment
      of incomplete ablation were associated with better overall survival in patients
      with incomplete ablation. CONCLUSIONS: This study demonstrated that incomplete
      ablation after RFA of HCC was associated with tumor size > 3 cm. Our data also
      suggest that aggressive further treatment of tumors with incomplete ablation
      aiming at complete tumor response improves overall survival.

PMID- 18095031
TI  - Multiple Genetic Polymorphisms of GSTP1 313AG, MDR1 3435CC, and MTHFR 677CC
      highly correlated with early relapse of breast cancer patients in Taiwan.
AB  - BACKGROUND: Genetic polymorphisms in drug-metabolizing enzymes, transporters,
      receptors, and other drug targets have been linked to inter-individual
      differences in the efficacy and toxicity of many medications. In the present
      study, multiple chemotherapeutic agent-related genetic polymorphisms, including
      GSTP1, MDR1, MTHFR, and TS tandem repeats, were analyzed in breast cancer
      patients and studied in correlation with the clinical outcome of patients
      receiving FEC adjuvant chemotherapy. METHODS: The genotypes from 192 stage II and
      III breast cancer patients who underwent operations and received six cycles of
      postoperative adjuvant chemotherapy (FEC) were determined by means of PCR-RFLP.
      The association of each genetic polymorphism with clinicopathological data of
      patients and early relapse status were analyzed. RESULTS: The results showed that
      the genotype distribution of GSTP1 A313G, MTHFR C677T, and TS 3R3R in Taiwanese
      subjects differed significantly from the distribution in Caucasians. After
      analysis of the relationship between the genotypes and clinicopathological data
      of the patients, a significant correlation was observed between postoperative
      early relapse in patients with genetic polymorphisms of both MDR1 3435CC and
      MTHFR 677CC (crude OR: 2.609, P = .013) and patients with additional GSTP1 313AG
      genetic polymorphism (crude OR: 2.833, P = .017). CONCLUSIONS: The results of the
      present study highly suggest that GSTP1, MDR1, and MTHFR genotypes could be
      prognostic factors for Taiwanese patients with breast cancer.

PMID- 18095032
TI  - Diminishing disparities: starting in our own backyards.

PMID- 18095033
TI  - Morbidity of ostomy takedown.
AB  - PURPOSE: Creation of a temporary ostomy is a surgical tool to divert stool from a
      more distal area of concern (anastomosis, inflammation, etc). To provide a true
      benefit, the morbidity/mortality from the ostomy takedown itself should be
      minimal. The aim of our study was therefore to evaluate our own experience and
      determine the complications and mortality of stoma closure in relation to the
      type and location of the respective ostomy. METHODS: Patients undergoing an
      elective takedown of a temporary ostomy at our teaching institution between
      January 1999 and July 2005 were included in our analysis, and the medical records
      were retrospectively reviewed. Excluded were only patients with relevant chart
      deficiencies and nonelective stoma revisions/takedowns. Data collected included
      general demographics; the type and location of the stoma; the operative
      technique; and the type, timing, and impact of complications. Perioperative
      morbidity was defined as complications occurring within 30 days from the
      operation. RESULTS: 156 patients (median age 45 years, range 18-85) were included
      in the analysis: 31 loop and 59 end colostomy reversals and 56 loop and 10 end
      ileostomy takedowns. Mean follow-up was 6 months. The overall mortality rate was
      low (0.65%, 1/156 patients). However, the morbidity rate was 36.5% (57 patients),
      with 6 (3.8%) systemic complications and 51 (32.7%) local complications. Minor
      would infection (34 patients, 21.8%) and postoperative ileus (9 patients, 5.7%)
      were the most common surgery-related complications, but they generally resolved
      with conservative management. Anastomotic leak and formation/persistence of an
      enterocutaneous fistula (6 patients, 3.8%) were the most serious local
      complications and required reintervention in all of the patients. Closure of a
      loop colostomy accounted for half and Hartmann reversals for one third of these
      complications, as opposed to ileostomy takedowns, which accounted for only one
      sixth (1.8% absolute risk). CONCLUSION: Takedown of a temporary ostomy has a low
      mortality but a nonnegligible morbidity. The stoma location (large vs. small
      bowel) has a higher impact than the type of stoma construction (end vs. loop) on
      the incidence and severity of complications.

PMID- 18095034
TI  - The rules of evidence-based medicine: can they be generalized to improve GI
      surgical practice?
AB  - Evidence-based surgical practice (EBSP) must be integrated into the educational
      curriculum for all surgeons. Independent of the compelling need for best
      practice, there are at least three compelling drivers: the exploding cost of
      health care demands evidence-based practice, patient safety is best supported by
      best evidence, and the medico-legal environment uses EBSP to pursue its goals.

PMID- 18095035
TI  - Introduction: new medical device technologies.

PMID- 18095036
TI  - "It's like crossing a bridge" complexities preventing physicians from discussing
      deactivation of implantable defibrillators at the end of life.
AB  - OBJECTIVE: To understand potential barriers to physician-initiated discussions
      about Implantable Cardioverter Defibrillator (ICD) deactivation in patients with
      advanced illness. DESIGN: Qualitative one-on-one interviews. PARTICIPANTS: Four
      electrophysiologists, 4 cardiologists, and 4 generalists (internists and
      geriatricians) from 3 states. APPROACH: Clinicians were interviewed using open
      ended questions to elicit their past experiences with discussing deactivating
      ICDs and to determine what barriers might impede these discussions. Transcripts
      of these interviews were analyzed using the qualitative method of constant
      comparison. RESULTS: Although many physicians believed that conversations about
      deactivating ICDs should be included in advance care planning discussions, they
      acknowledged that they rarely did this. Physicians indicated that there was
      something intrinsic to the nature of these devices that makes it inherently
      difficult to think of them in the same context as other management decisions at
      the end of a patient's life. Other explanations physicians gave as to why they
      did not engage in conversations included: the small internal nature of these
      devices and hence absence of a physical reminder to discuss the ICD, the absence
      of an established relationship with the patient, and their own general concerns
      relating to withdrawing care. CONCLUSION: Whereas some of the barriers to
      discussing ICD deactivation are common to all forms of advance care planning,
      ICDs have unique characteristics that make these conversations more difficult.
      Future educational interventions will need to be designed to teach physicians how
      to improve communication with patients about the management of ICDs at the end of
      life.

PMID- 18095037
TI  - "That's like an act of suicide" patients' attitudes toward deactivation of
      implantable defibrillators.
AB  - OBJECTIVE: To understand potential patient barriers to discussions about
      implantable cardioverter defibrillator (ICD) deactivation in patients with
      advanced illness. DESIGN: Qualitative focus groups. PARTICIPANTS: Fifteen
      community-dwelling, ambulatory patients with ICDs assigned to focus groups based
      on duration of time since implantation and whether they had ever received a shock
      from their device. APPROACH: A physician and a social worker used a predetermined
      discussion guide to moderate the groups, and each session was audiotaped and
      subsequently transcribed. Transcripts were analyzed using the method of constant
      comparison. RESULTS: No participant had ever discussed deactivation with their
      physician nor knew that deactivation was an option. Patients expressed a great
      deal of anxiety about receiving shocks from their device. Participants discussed
      why they needed the device and expressed desire for more information about the
      device; however, they would not engage in conversations about deactivating the
      ICD. One patient described deactivation "like an act of suicide" and all patients
      believed that the device was exclusively beneficial. Patients also expressed a
      desire to have their physician make the decision about deactivation. CONCLUSIONS:
      None of the patients in our study knew that they might need to deactivate their
      ICD as their health worsens. These community-dwelling outpatients were not
      willing to discuss the issue of ICD deactivation and their attitudes about
      deactivation might impede patients from engaging in these conversations. These
      findings are in contrast to findings in other advance care planning research and
      may be related to the unique nature of the ICD.

PMID- 18095038
TI  - Cardiac device implantation in the United States from 1997 through 2004: a
      population-based analysis.
AB  - OBJECTIVE: Use of cardiac devices has been increasing rapidly along with concerns
      over their safety and effectiveness. This study used hospital administrative data
      to assess cardiac device implantations in the United States, selected
      perioperative outcomes, and associated patient and hospital characteristics.
      METHODS: We screened hospital discharge abstracts from the 1997-2004 Healthcare
      Cost and Utilization Project Nationwide Inpatient Samples. Patients who underwent
      implantation of pacemaker (PM), automatic cardioverter/defibrillator (AICD), or
      cardiac resynchronization therapy pacemaker (CRT-P) or defibrillator (CRT-D) were
      identified using ICD-9-CM procedure codes. Outcomes ascertainable from these data
      and associated hospital and patient characteristics were analyzed. MEASUREMENTS
      AND MAIN RESULTS: Approximately 67,000 AICDs and 178,000 PMs were implanted in
      2004 in the United States, increasing 60% and 19%, respectively, since 1997.
      After FDA approval in 2001, CRT-D and CRT-P reached 33,000 and 7,000 units per
      year in the United States in 2004. About 70% of the patients were aged 65 years
      or older, and more than 75% of the patients had 1 or more comorbid diseases.
      There were substantial decreases in length of stay, but marked increases in
      charges, for example, the length of stay of AICD implantations halved (from 9.9
      days in 1997 to 5.2 days in 2004), whereas charges nearly doubled (from $66,000
      in 1997 to $117,000 in 2004). Rates of in-hospital mortality and complications
      fluctuated slightly during the period. Overall, adverse outcomes were associated
      with advanced age, comorbid conditions, and emergency admissions, and there was
      no consistent volume-outcome relationship across different outcome measures and
      patient groups. CONCLUSIONS: The numbers of cardiac device implantations in the
      United States steadily increased from 1997 to 2004, with substantial reductions
      in length of stay and increases in charges. Rates of in-hospital mortality and
      complications changed slightly over the years and were associated primarily with
      patient frailty.

PMID- 18095039
TI  - Interest in the use of computerized patient portals: role of the provider-patient
      relationship.
AB  - BACKGROUND: Bioinformatics experts are developing interactive patient portals to
      help those living with diabetes and other chronic diseases to better manage their
      conditions. However, little is known about what influences patients' desires to
      use this technology. OBJECTIVE: To discern the impact of the provider-patient
      relationship on interest in using a web-based patient portal. DESIGN: Qualitative
      analysis of focus groups. PARTICIPANTS: Ten focus groups involving 39 patients
      (range 2-7) recruited from four primary care practices. APPROACH: A qualitative
      approach was used, which involved reading transcribed texts until a consensus was
      reached on data interpretation. An intercoder reliability kappa score (0.89) was
      determined by comparing the provider-patient relationship talk selected by the
      two coders. A conceptual framework was developed, which involved the development
      and refinement of a codebook and the application of it to the transcripts.
      RESULTS: Interest in the portal was linked to dissatisfaction with the provider
      patient relationship, including dissatisfaction with provider
      communication/responsiveness, the inability to obtain medical information, and
      logistical problems with the office. Disinterest in the portal was linked to
      satisfaction with the provider-patient relationship, including provider
      communication/responsiveness, difficulty in using the portal, and fear of losing
      relationships and e-mail contact with the provider. No patient identified
      encrypted e-mail communication through the portal as an advantage. CONCLUSIONS:
      Promoting the use of computerized portals requires patient-based adaptations.
      These should include ease of use, direct provider e-mail, and reassurances that
      access and interpersonal relationships will not be lost. Education is needed
      about privacy concerns regarding traditional e-mail communication.

PMID- 18095040
TI  - Evaluation of clinical innovation: a gray zone in the ethics of modern clinical
      practice?
AB  - BACKGROUND: Various stakeholders can have differing opinions regarding ethical
      review when introducing new procedures with patients. OBJECTIVE: This pilot study
      examines the way in which Research Ethics Boards (REBs; Institutional Review
      Boards) and clinical biochemists (CBs; laboratory medicine specialists) differ in
      their interpretation of what is research and what should be considered common
      practice versus innovation versus experimentation when introducing new procedures
      with patients. It also explores whether these groups agree on who is responsible
      for the ethical review of new procedures. METHODS: A validated case scenario for
      the introduction of a new diagnostic test into clinical practice was sent to CBs
      and REBs across Canada. Participants were asked to determine whether the scenario
      constituted research; whether the test procedure should be considered as
      experimental, innovative, or commonly accepted care; and whether the project
      required approval by a REB and, if not, who should be responsible for ethical
      review. RESULTS: Results showed 81% of 37 CBs and 52% of 27 REBs identified the
      scenario as research. Responsibility for ethical review was assigned to REBs by
      44% of REBs and 54% of CBs. Of all participants, 53% classified the test
      procedure as 'innovative', 8% as 'experimental', whereas 17% classified it as
      'commonly accepted'. CONCLUSIONS: This pilot study indicates a substantial
      variation in the ethical assessment of innovation in clinical care. This suggests
      the need to further elaborate on the types of innovation in health care and
      categorize the nature of the risks associated with each.

PMID- 18095041
TI  - Improving sedative-hypnotic prescribing in older hospitalized patients: provider
      perceived benefits and barriers of a computer-based reminder.
AB  - BACKGROUND: Older adults are commonly prescribed sedative-hypnotic (SH)
      medications when hospitalized, yet these drugs are associated with important
      adverse effects such as falls and delirium. OBJECTIVE: To identify provider
      perceived benefits or barriers of a computer-based reminder regarding appropriate
      use of SH medications. DESIGN: Qualitative study using semi-structured
      interviews. PARTICIPANTS AND SETTING: Thirty-six house staff physicians at a
      university hospital. MEASUREMENTS: Information was collected regarding the
      experiences of prescribing an SH using a computer order entry system with a
      reminder intervention. Clinicians were asked about their perceptions of the
      reminder and what they found most and least useful about it. Responses were
      analyzed using grounded theory methodology. RESULTS: The 36 participants
      (including 29 interns) had prescribed an SH medication for a hospitalized patient
      over age 65 years. Three themes associated with benefits of a computer reminder
      were identified: increasing awareness of safety, including risk of delirium,
      falls, and general patient safety risks; usefulness of information technology;
      and the value of the educational content, including geriatric pharmacology review
      and nonpharmacologic treatment options. Barriers included the demands of the
      reminder with regard to time needed to read the reminder, the role of clinician
      experience with regard to preserving clinical autonomy, and the information
      content of the reminder, including its being too basic or not relevant for a
      particular patient. The mean satisfaction rating for the reminder was 8.5 (+/-0.9
      SD), with 10 indicating high satisfaction. CONCLUSIONS: Improving decision
      support systems involves an understanding of how clinicians respond to real-time
      strategies encouraging better prescribing.

PMID- 18095042
TI  - Performance of a web-based clinical diagnosis support system for internists.
AB  - BACKGROUND: Clinical decision support systems can improve medical diagnosis and
      reduce diagnostic errors. Older systems, however, were cumbersome to use and had
      limited success in identifying the correct diagnosis in complicated cases.
      OBJECTIVE: To measure the sensitivity and speed of "Isabel" (Isabel Healthcare
      Inc., USA), a new web-based clinical decision support system designed to suggest
      the correct diagnosis in complex medical cases involving adults. METHODS: We
      tested 50 consecutive Internal Medicine case records published in the New England
      Journal of Medicine. We first either manually entered 3 to 6 key clinical
      findings from the case (recommended approach) or pasted in the entire case
      history. The investigator entering key words was aware of the correct diagnosis.
      We then determined how often the correct diagnosis was suggested in the list of
      30 differential diagnoses generated by the clinical decision support system. We
      also evaluated the speed of data entry and results recovery. RESULTS: The
      clinical decision support system suggested the correct diagnosis in 48 of 50
      cases (96%) with key findings entry, and in 37 of the 50 cases (74%) if the
      entire case history was pasted in. Pasting took seconds, manual entry less than a
      minute, and results were provided within 2-3 seconds with either approach.
      CONCLUSIONS: The Isabel clinical decision support system quickly suggested the
      correct diagnosis in almost all of these complex cases, particularly with key
      finding entry. The system performed well in this experimental setting and merits
      evaluation in more natural settings and clinical practice.

PMID- 18095043
TI  - Programmable infusion pumps in ICUs: an analysis of corresponding adverse drug
      events.
AB  - BACKGROUND: Patients in intensive care units (ICUs) frequently experience adverse
      drug events involving intravenous medications (IV-ADEs), which are often
      preventable. OBJECTIVES: To determine how frequently preventable IV-ADEs in ICUs
      match the safety features of a programmable infusion pump with safety software
      ("smart pump") and to suggest potential improvements in smart-pump design.
      DESIGN: Using retrospective medical-record review, we examined preventable IV
      ADEs in ICUs before and after 2 hospitals replaced conventional pumps with smart
      pumps. The smart pumps alerted users when programmed to deliver duplicate
      infusions or continuous-infusion doses outside hospital-defined ranges.
      PARTICIPANTS: 4,604 critically ill adults at 1 academic and 1 nonacademic
      hospital. MEASUREMENTS: Preventable IV-ADEs matching smart-pump features and
      errors involved in preventable IV-ADEs. RESULTS: Of 100 preventable IV-ADEs
      identified, 4 involved errors matching smart-pump features. Two occurred before
      and 2 after smart-pump implementation. Overall, 29% of preventable IV-ADEs
      involved overdoses; 37%, failures to monitor for potential problems; and 45%,
      failures to intervene when problems appeared. Error descriptions suggested that
      expanding smart pumps' capabilities might enable them to prevent more IV-ADEs.
      CONCLUSION: The smart pumps we evaluated are unlikely to reduce preventable IV
      ADEs in ICUs because they address only 4% of them. Expanding smart-pump
      capabilities might prevent more IV-ADEs.

PMID- 18095044
TI  - Simulation technology for skills training and competency assessment in medical
      education.
AB  - Medical education during the past decade has witnessed a significant increase in
      the use of simulation technology for teaching and assessment. Contributing
      factors include: changes in health care delivery and academic environments that
      limit patient availability as educational opportunities; worldwide attention
      focused on the problem of medical errors and the need to improve patient safety;
      and the paradigm shift to outcomes-based education with its requirements for
      assessment and demonstration of competence. The use of simulators addresses many
      of these issues: they can be readily available at any time and can reproduce a
      wide variety of clinical conditions on demand. In lieu of the customary (and
      arguably unethical) system, whereby novices carry out the practice required to
      master various techniques--including invasive procedures--on real patients,
      simulation-based education allows trainees to hone their skills in a risk-free
      environment. Evaluators can also use simulators for reliable assessments of
      competence in multiple domains. For those readers less familiar with medical
      simulators, this article aims to provide a brief overview of these educational
      innovations and their uses; for decision makers in medical education, we hope to
      broaden awareness of the significant potential of these new technologies for
      improving physician training and assessment, with a resultant positive impact on
      patient safety and health care outcomes.

PMID- 18095045
TI  - Economic implications of potential changes to regulatory and reimbursement
      policies for medical devices.
AB  - OBJECTIVE: To evaluate the impact of regulatory scenarios on the financial
      viability of medical device companies. DESIGN: We developed a model to calculate
      the expected net present value of a hypothetical product throughout preclinical
      development, clinical testing, regulatory approval, and postmarketing. We tested
      3 scenarios: (1) the current regulatory environment; (2) a scenario in which
      medical devices are subject to the same evidence standards required for
      pharmaceuticals; and (3) a scenario consistent with the Coverage with Evidence
      Development: Coverage with Study Participation (CSP) policy proposed by the
      Centers for Medicare and Medicaid Services, whereby Medicare will pay for
      beneficiaries to receive new devices that are not currently determined to be
      "reasonable and necessary" if the patients participate in clinical studies or
      registries. MEASUREMENTS AND MAIN RESULTS: When applying assumptions consistent
      with the implantable cardioverter-defibrillator market, the net present value at
      the start of development was an estimated $553 million in the current regulatory
      environment, $322 million in the pharmaceutical scenario, and $403 million in the
      CSP scenario. Sensitivity analyses showed that the device industry would likely
      be profitable in all 3 scenarios over a range of assumptions. CONCLUSIONS: The
      environment in which the medical device industry operates is financially
      attractive. Furthermore, when compared with the alternative of applying the same
      evidence standards for pharmaceuticals to medical devices, the CSP policy offers
      improved financial incentives for medical device companies.

PMID- 18095046
TI  - Who is responsible for evaluating the safety and effectiveness of medical
      devices? The role of independent technology assessment.
AB  - INTRODUCTION: The global medical technology industry brings thousands of devices
      to market every year. However, significant gaps persist in the scientific
      literature, in the medical device approval process, and in the realm of
      postmarketing surveillance. Although thousands of drugs obtain approval only
      after review in randomized controlled trials, relatively few new medical devices
      are subject to comparable scrutiny. OBJECTIVE: To improve health outcomes, we
      must enhance our scrutiny of medical devices, and, without simply deferring to
      the Food and Drug Administration, we must ask ourselves: Who is responsible for
      evaluating the safety and effectiveness of medical devices? CONCLUSIONS:
      Technology assessments by independent organizations are a part of the solution to
      this challenge and may motivate further research focused on patient outcomes.

PMID- 18095047
TI  - Trial registration for public trust: making the case for medical devices.
AB  - Recently, several pharmaceutical companies have been shown to have withheld
      negative clinical trial results from the public. These incidents have resulted in
      a concerted global effort to register all trials at inception, so that all
      subsequent results can be tracked regardless of whether they are positive or
      negative. These trial registration policies have been driven in large part by
      concern about the pharmaceutical sector. The medical device industry is much
      smaller, and different from the pharmaceutical industry in some fundamental ways.
      This paper examines the issues surrounding registration of device trials and
      argues that these differences with pharmaceutical should not exempt device trials
      from registration.

PMID- 18095048
TI  - Within you/without you: biotechnology, ontology, and ethics.
AB  - As Implantable Cardioverter Defibrillators (ICDs) have become more common,
      ethical issues have arisen regarding the deactivation of these devices. Goldstein
      et al., have shown that both patients and cardiologists consider ICD deactivation
      to be different from the discontinuation of other life-sustaining treatments. It
      cannot be argued ethically that ICDs raise new questions about the distinction
      between withholding and withdrawing treatment, and neither the fact that they are
      used intermittently, nor the duration of therapy, nor the mere fact that they are
      located inside the body can be considered unique to these devices and morally
      decisive. However, frequent allusions to the fact that they are located inside
      the body might provide a clue about what bothers patients and physicians. As
      technology progresses, some interventions seem to become a part of the patient as
      a unified whole person, completely replacing body parts and lost physiological
      functions rather than merely substituting for impaired structure and function. If
      a life-sustaining intervention can be considered a "replacement"--a part of the
      patient as a unified whole person--then it seems that deactivation is better
      classified as a case of killing rather than a case of forgoing a life-sustaining
      treatment. ICDs are not a "replacement" therapy in this sense. The deactivation
      of an ICD is best classified, under the proper conditions, as the forgoing of an
      extraordinary means of care. As technology becomes more sophisticated, however,
      and new interventions come to be best classified as "replacements" (a heart
      transplant would be a good example), "discontinuing" these interventions should
      be much more morally troubling for those clinicians who oppose euthanasia and
      assisted suicide.

PMID- 18095049
TI  - Telecardiology and remote monitoring of implanted electrical devices: the
      potential for fresh clinical care perspectives.
AB  - Telecardiology may help confront the growing burden of monitoring the reliability
      of implantable defibrillators/pacemakers. Herein, we suggest that the evolving
      capabilities of implanted devices to monitor patients' status (heart rhythm,
      fluid overload, right ventricular pressure, oximetry, etc.) may imply a shift
      from strictly device-centered follow-up to perspectives centered on the patient
      (and patient-device interactions). Such approaches could provide improvements in
      health care delivery and clinical outcomes, especially in the field of heart
      failure. Major professional, policy, and ethical issues will have to be overcome
      to enable real-world implementation. This challenge may be relevant for the
      evolution of our health care systems.

PMID- 18095050
TI  - Proteomics as a method for early detection of cancer: a review of proteomics,
      exhaled breath condensate, and lung cancer screening.
AB  - The study of expressed proteins in neoplasia is undergoing a revolution with the
      advent of proteomic analysis. Unlike genomic studies where individual changes may
      have no functional significance, protein expression is closely aligned with
      cellular activity. This perspective will review proteomics as a method of
      detecting markers of neoplasia with a particular emphasis on lung cancer and the
      potential to sample the lung by exhaled breath condensate (EBC). EBC collection
      is a simple, new, and noninvasive technique, which allows sampling of lower
      respiratory tract fluid. EBC enables the study of a wide variety of biological
      markers from low molecular weight mediators to macromolecules, such as proteins,
      in a range of pulmonary diseases. EBC may be applied to the detection of lung
      cancer where it could be a tool in early diagnosis. This perspective will explore
      the potential of applying proteomics to the EBC from lung cancer patients as an
      example of detecting potential biomarkers of disease and progression.

PMID- 18095051
TI  - Computerized clinical decision support: will it transform healthcare?

PMID- 18095052
TI  - Randomized, controlled, blinded trial of Tissucol/Tisseel for mesh fixation in
      patients undergoing Lichtenstein technique for primary inguinal hernia repair:
      rationale and study design of the TIMELI trial.
AB  - BACKGROUND: Complications associated with sutured mesh fixation following open
      groin hernia repair have prompted surgeons to evaluate methods of atraumatic
      fixation such as the use of human fibrin glue. Small trials with Tissucol/Tisseel
      fibrin glue (Baxter Healthcare, Deerfield, IL, USA) have shown promising results
      that warrant further investigation. METHODS: TIMELI (Tissucol/Tisseel for MEsh
      fixation in LIchtenstein hernia repair) is an international, controlled,
      randomized, patient- and evaluator-blinded study that is comparing mesh fixation
      with Tissucol or sutures in patients with inguinal hernia. The primary endpoint
      evaluates the incidence of disabling complications (chronic pain and/or numbness
      and/or groin discomfort) at 12 months post-surgery. RESULTS: Patient enrolment
      started in February 2006 and ended on 19 April 2007, with a total of 325 patients
      recruited. Initial results are expected in early 2008. CONCLUSIONS: TIMELI is a
      major international trial that will provide important information on the efficacy
      and safety of Tissucol, compared with sutures, for mesh fixation in patients
      undergoing Lichtenstein technique for primary inguinal hernia repair.

PMID- 18095053
TI  - Biological activity of antitumoural MGBG: the structural variable.
AB  - The present study aims at determining the structure-activity relationships
      (SAR's) ruling the biological function of MGBG (methylglyoxal
      bis(guanylhydrazone)), a competitive inhibitor of S-adenosyl-L-methionine
      decarboxylase displaying anticancer activity, involved in the biosynthesis of the
      naturally occurring polyamines spermidine and spermine. In order to properly
      understand its biochemical activity, MGBG's structural preferences at
      physiological conditions were ascertained, by quantum mechanical (DFT)
      calculations.

PMID- 18095054
TI  - Near infrared spectroscopy compared to liquid chromatography coupled to mass
      spectrometry and capillary electrophoresis as a detection tool for peptide
      reaction monitoring.
AB  - Peptide interaction is normally monitored by liquid chromatography (LC), liquid
      chromatography coupled to mass spectrometry (LC-MS), mass spectrometric (MS)
      methods such as MALDI-TOF/MS or capillary electrophoresis (CE). These analytical
      techniques need to apply either high pressure or high voltages, which can cause
      cleavage of newly formed bondages. Therefore, near infrared reflectance
      spectroscopy (NIRS) is presented as a rapid alternative to monitor the
      interaction of glutathione and oxytocin, simulating physiological conditions.
      Thereby, glutathione can act as a nucleophile with oxytocin forming four new
      conjugates via a disulphide bondage. Liquid chromatography coupled to UV (LC-UV)
      and mass spectrometry via an electrospray ionisation interface (LC-ESI-MS)
      resulted in a 82% and a 78% degradation of oxytocin at pH 3 and a 5% and a 7%
      degradation at pH 6.5. Capillary electrophoresis employing UV-detection (CE-UV)
      showed a 44% degradation of oxytocin. LC and CE in addition to the NIRS are found
      to be authentic tools for quantitative analysis. Nevertheless, NIRS proved to be
      highly suitable for the detection of newly formed conjugates after separating
      them on a thin layer chromatography (TLC) plate. The recorded fingerprint in the
      near infrared region allows for a selective distinct qualitative identification
      of conjugates without the need for expensive instrumentation such as quadrupole
      or MALDI-TOF mass spectrometers. The performance of the established NIRS method
      is compared to LC and CE; its advantages are discussed in detail.

PMID- 18095055
TI  - Expression profiles of the organic acid metabolism-associated genes during rat
      liver regeneration.
AB  - In this study, 55 of the organic acid metabolism-involved genes were primarily
      confirmed to be associated with liver regeneration (LR) by bioinformatics and
      gene expression profiling analysis. Number of the initially and totally expressed
      genes occurring in initiation phase of LR, G(0)/G(1), cell proliferation, cell
      differentiation and liver tissue structure-function reconstruction were 21, 5,
      33, 1 and 40, 20, 174, 44, respectively, illustrating that genes were initially
      expressed mainly in initiation stage, and worked in different phases. 151 times
      up-regulation and 114 times down-regulation as well as 14 types of expression
      patterns showed the diversification and complication of genes expression changes.
      It is inferred from the above gene expression changes and patterns that acetate
      biosynthesis enhanced at forepart, propionate biosynthesis at forepart, prophase
      and early metaphase, pyruvate biosynthesis at forepart, metaphase and anaphase,
      succinate biosynthesis at forepart and anaphase; malate biosynthesis in metaphase
      and N-acetylneuraminate biosynthesis at 36, 66 and 96 h. Whereas, carnitine
      biosynthsis attenuates at forepart and prophase, enhancement at middle metaphase;
      isocitrate in the forepart, quinolinate at forepart and early metaphase, creatine
      at early metaphase and fumarate at anaphase perform the restrained biosynthesis,
      respectively; catabolisms of propionate and pyruvate were depressed in metaphase.

PMID- 18095056
TI  - Phylogenetic position of Oxygyne shinzatoi (Burmanniaceae) inferred from 18S rDNA
      sequences.
AB  - The genus Oxygyne comprises three species disjunctly distributed in Africa and
      Japan and is the least examined genus of the Burmanniaceae due to the scarcity of
      living material. We obtained living samples of Oxygyne shinzatoi and examined the
      phylogenetic position of this species on the basis on the 18S rDNA sequence.
      Oxygne shinzatoi was consistently found to belong to the monophyletic group of
      tribe Thismieae, but its position in the tribe differed depending on the criteria
      applied (maximum parsimony, maximum likelihood, Bayesian inference). Distance
      analysis from the most recent common ancestor indicated that O. shinzatoi had the
      lowest substitution rate among the species of tribe Thismieae. Combined with
      recent knowledge of basic chromosome numbers and substitution rate
      characteristics, O. shinzatoi can be considered to be one of the basal taxon of
      tribe Thismieae.

PMID- 18095057
TI  - Bone quality: the material and structural basis of bone strength.
AB  - The material composition and structural design of bone determine its strength.
      Structure determines loads that can be tolerated but loads also determine
      structure. Bone modifies its material composition and structure to accommodate
      loads by adaptive modeling and remodeling. Adaptation is successful during growth
      but not aging because accumulating insults, including a reduction in the volume
      of bone formed in the basic multicellular unit (BMU), increased resorption in the
      BMU, increased remodeling rate in midlife in women and in some men because of sex
      hormone deficiency, and in both sexes in old age as a consequence of secondary
      hyperparathyroidism and reduced periosteal bone formation, all of which
      compromises the material composition of bone and its structure. An understanding
      of the mechanisms of adaptation and failed adaptation provides rational
      approaches to interventions that can prevent or restore bone fragility.

PMID- 18095058
TI  - Steroid and xenobiotic receptor mediates a novel vitamin K2 signaling pathway in
      osteoblastic cells.
AB  - The nuclear receptor steroid and xenobiotic receptor (SXR) is a transcriptional
      regulator activated by various biological and xenobiotic substances. We have
      recently shown that SXR is expressed in bone and that this receptor is critical
      for bone metabolism, particularly in osteoblastic cells. Vitamin K2, one of the
      critical nutrients in bone metabolism, has been demonstrated that it is a potent
      SXR agonist and modulates the expression of various bone-related genes in
      osteoblastic cells. Using microarray analysis, we identified novel SXR target
      genes that were activated by vitamin K2 in osteoblastic cells. Among them, a
      small leucine-rich repeat proteoglycan, tsukushi, has been shown to contribute to
      collagen accumulation, and the protein may interact with another vitamin K2
      inducible SXR target, matrilin-2, a member of the matrilin family that functions
      as collagen adaptors. Besides functioning as a xenobiotic biosensor, our findings
      show that SXR is also a vitamin K2 target and an important transcriptional factor
      that regulates bone homeostasis in bone cells.

PMID- 18095059
TI  - Bone marrow stromal cell lines having high potential for osteoclast-supporting
      activity express PPARgamma1 and show high potential for differentiation into
      adipocytes.
AB  - Bone marrow stromal cells support osteoclast differentiation by expressing
      receptor activator of NF-kB ligand (RANKL). Although several bone marrow stromal
      cell lines have been established and characterized, the differentiation stage of
      the supporting cells for osteoclast differentiation remains unclear. We have
      established several bone marrow stromal cell lines from transgenic mice harboring
      the temperature-sensitive SV40 large T antigen. Some of these temperature
      sensitive bone marrow stromal cell lines (TSB cell lines) support osteoclast
      differentiation and differentiate into osteoblasts, suggesting that osteoblast
      precursor cells support osteoclast differentiation. Here we show that the TSB
      cell lines that support osteoclast differentiation also expressed peroxisome
      proliferator-activated receptor gamma1 (PPARgamma1) and were able to
      differentiate into adipocytes. PPARgamma1 is an alternatively spliced form of
      PPARgamma that is responsible for the adipocyte differentiation and expressed in
      the adipocyte precursor cells. Immunofluorescence analysis of TSB cell lines and
      primary bone marrow stromal cells by use of anti-PPARgamma and anti-RANKL
      antibodies showed that fluorescent signals for RANKL were observed in the cells
      that expressed PPARgamma. Furthermore, activation of adipocyte differentiation by
      a PPARgamma agonist led to decreased RANKL expression. These results demonstrate
      that PPARgamma1-positive precursor cells for osteoblasts and adipocytes expressed
      RANKL and supported osteoclastogenesis.

PMID- 18095060
TI  - Alendronate treatment promotes bone formation with a less anisotropic
      microstructure during intramembranous ossification in rats.
AB  - There are safety concerns regarding administration of bisphosphonates to
      children. Little is known about the effects of bisphosphonates on bone matrix
      organization during bone modeling. The present study examined the effects of
      alendronate (ALN) on bone matrices formed by intramembranous ossification in the
      appendicular growing skeleton. ALN was administered to 1-week-old Sprague-Dawley
      rats at a dose of 0, 35, or 350 microg/kg/week for 4 or 8 weeks. The position of
      femoral diaphysis formed exclusively by intramembranous ossification was
      identified, and cross sections of cortical bone at this position were analyzed.
      Bone mineral density (BMD) and geometric parameters were evaluated using
      peripheral quantitative computed tomography. The preferential orientation degree
      of biological apatite (BAp) crystals in the bone longitudinal direction, which
      shows the degree of bone matrix anisotropy, was evaluated using microbeam X-ray
      diffraction analysis. We analyzed bone histomorphometrical parameters and
      performed bone nanomechanical tests to examine the material properties of newly
      developing cortical bone. The preferential orientation degree of BAp crystals
      significantly decreased in 35 microg/kg/week ALN-treated groups compared with
      vehicle-treated groups, although there were no significant differences in BMD
      between the two groups. The periosteal mineral apposition rate significantly
      increased in the 35 microg/kg/week ALN-treated group. We found a high negative
      correlation between bone matrix anisotropy and the regional periosteal mineral
      apposition rate (r = -0.862, P < 0.001). Nanomechanical tests revealed that 35
      microg/kg/week ALN administration caused deterioration of the material properties
      of the bone microstructure. These new findings suggest that alendronate affects
      bone matrix organization and promotes bone formation with a less anisotropic
      microstructure during intramembranous ossification.

PMID- 18095061
TI  - The cost-effectiveness of risedronate treatment in Japanese women with
      osteoporosis.
AB  - We constructed a mathematical model for assessing the cost-effectiveness of
      providing BMD (bone mineral density) scans to Japanese women aged 55 years and
      over and treating, with risedronate, those that are shown to be osteoporotic.
      Fracture rates, cost data, utility values, and the increased risks of fractures
      associated with T-score and vertebral fracture history were taken from published
      literature. We estimated the cost of fractures avoided due to risedronate
      treatment, allowing the net changes in cost, incorporating both intervention and
      fracture costs to be calculated. The QALYs (quality adjusted life years) gained
      through treatment were calculated enabling cost per QALY ratios to be presented.
      Further analyses were undertaken assuming treatment was reserved for older women
      and/or those who had sustained a vertebral fracture in the previous 2 years. Cost
      per QALY values were inversely related to absolute risk of fracture. Assuming a
      cost per QALY value threshold of US dollars 100,000, we concluded that providing
      BMD scans to women aged 70 years and over who had sustained a vertebral fracture
      in the previous 2 years and treating those that were osteoporotic was cost
      effective. However, providing BMD scans for women without a vertebral fracture in
      the previous 2 years was not cost-effective, even in women aged 85 years and
      older.

PMID- 18095062
TI  - Relationships between the insulin-like growth factor I (IGF-I) receptor gene
      G3174A polymorphism, serum IGF-I levels, and bone mineral density in
      postmenopausal Korean women.
AB  - We investigated the relationships between the IGF-I receptor gene G3174A
      polymorphism, serum IGF-I levels, and bone mineral density (BMD) in
      postmenopausal Korean women. The IGF-I receptor gene G3174A polymorphism was
      analyzed in 367 postmenopausal Korean women. Serum levels of IGF-I, bone turnover
      markers (osteocalcin, bone alkaline phosphatase, carboxy-terminal cross-linking
      telopeptide of type I collagen), and BMD at the lumbar spine and proximal femur
      were measured. The frequencies of the AA, GA, and GG genotypes were 10.9%, 44.1%,
      and 45.0%, respectively. BMD at the lumbar spine was significantly higher for the
      AA genotype than the other genotypes and showed an A allelic dose effect;
      however, no significant differences in BMD were observed at the proximal femur
      with respect to genotype. No differences were noted between the three genotypes
      in terms of serum levels of IGF-I or bone turnover markers. Women with low BMD
      showed a lower prevalence of the AA genotype and A allele than age-matched women
      with normal BMD. Women with the AA genotype were found to have about half the
      risk of a low BMD than women with other genotypes. In conclusion, IGF-I receptor
      gene G3174A polymorphism is associated with lumbar spine BMD in postmenopausal
      Korean women.

PMID- 18095063
TI  - The relationship of an Asian-specific screening tool for osteoporosis to
      vertebral deformity and osteoporosis.
AB  - An Asian-specific screening tool for osteoporosis, the so-called OSTA index, was
      devised and is likely to be helpful in determining which postmenopausal women
      need bone mineral density (BMD) measurement. Besides BMD, prevalent vertebral
      fracture is a strong risk factor for future fractures. However, the relationship
      of the OSTA index to prevalent vertebral fractures is currently unknown. In this
      study, we evaluated the performance of the OSTA index in elderly Thai women and
      assessed the relationship of the index to prevalent vertebral deformities.
      Subjects consisted of 741 healthy Thai elderly women. BMD was measured by DEXA
      and T-score <or=2.5 SD is defined as osteoporosis. Prevalent vertebral
      deformities were determined by morphometric X-ray absorptiometry. OSTA index >-1
      is classified as having low risk of osteoporosis, -1 to -4 as intermediate risk
      and, <-4 as high risk. Data were expressed as mean +/- SD. The mean age and body
      weight of subjects were 67 +/- 4.8 years and 57.8 +/- 8.7 kg, respectively. The
      area under the ROC curve for OSTA index to identify osteoporosis at femoral neck
      and lumbar spine was 0.80 and 0.72, respectively. Femoral neck osteoporosis was
      found in 40.4%, 6.3%, and 2.4% of subjects with high-risk, intermediate-risk, and
      low-risk OSTA indexes, respectively. With regard to vertebral deformities, the
      area under the ROC curve relating OSTA index to vertebral deformities was 0.70 (P
      < 0.001). The prevalence of vertebral deformities in according to the OSTA index
      was 19.2% in the high-risk, 7.9% in the intermediate-risk, and 2.8% in the low
      risk group. We concluded that the OSTA index can be of assistance in the
      selection of postmenopausal women for BMD measurement. In addition, this index
      may be helpful in the identification of postmenopausal women with vertebral
      deformity and those who need antifracture treatments.

PMID- 18095064
TI  - Characterization of a new experimental model of osteoporosis in rabbits.
AB  - To characterize an experimental model of osteoporosis in rabbits induced either
      by ovariectomy (OVX), glucocorticoids, or by a combination of both. Thirty-five
      rabbits were randomly allocated into five groups: bilateral OVX, daily
      methylprednisolone hemisuccinate (MPH) injections at a 1.5 mg/kg/day dose for 4
      consecutive weeks (MPH group), or variable dose of MPH between 0.5 and 2
      mg/kg/day in combination with OVX (OVX + MPH at low, medium, and high dose).
      Twenty-two animals were killed 6 weeks after OVX, and 13 were killed 16 weeks
      later. Dual-energy X-ray absorptiometry was obtained at baseline and 6 and 16
      weeks after OVX. High-resolution magnetic resonance imaging (MRI) was carried out
      at 0 and 6 weeks after OVX. Glucose, total cholesterol, triglyceride, and
      oestradiol blood levels before and 16 weeks after OVX were determined. Bone
      mineral density (BMD) decreased significantly at lumbar spine in MPH and OVX +
      MPH medium-dose groups, and at global knee and subchondral bone of the knee in
      MPH, OVX + MPH low- and medium-dosage groups (P < 0.05). BMD variations in OVX
      rabbits were not significant in any of the three anatomical locations analyzed.
      BMD variation 16 weeks after OVX was significant at lumbar spine and global knee
      in the OVX + MPH medium-dose group and only at global knee in the OVX + MPH low
      dose group (P < 0.05). MRI did not show bone or cartilage changes. Osteoporosis
      can be induced experimentally in rabbits through isolated MPH or by a combination
      of OVX and medium dose corticosteroid for 4 weeks. OVX alone was not sufficient
      to induce osteoporosis.

PMID- 18095065
TI  - An assessment of the use of quantitative ultrasound and the Osteoporosis Self
      Assessment Tool for Asians in determining the risk of nonvertebral fracture in
      postmenopausal Chinese women.
AB  - This cross-sectional study aims to assess the effectiveness of a simple,
      noninvasive scoring system, the Osteoporosis Self-Assessment Tool for Asians
      (OSTA), and quantitative bone ultrasound (QUS) in assessing nonvertebral fracture
      risk in Chinese postmenopausal women. A group of 513 community-dwelling women
      including 271 postmenopausal individuals participated in this study. Speed of
      sound (SOS m/s) at the radius, phalanx, and tibia were assessed by using the
      Omnisense prototype (Sunlight Ltd., Israel). Body height and weight were
      measured, and body mass index (BMI) and OSTA indices were calculated. Self
      reported fractures were identified using a structured questionnaire. Phalanx SOS
      was significantly lower among postmenopausal women with a history of nonvertebral
      fracture occurred after menopause than those without (3755 m/s vs. 3841 m/s, P =
      0.017, adjusted for age and weight), with an AUC of 0.66. The AUC of the OSTA for
      predicting nonvertebral fracture occurred after menopause was 0.64. SOS at the
      radius, phalanx, and tibia showed a positive correlation with OSTA index (r =
      0.376-0.401, P < 0.001). The prevalence of nonvertebral fractures also increased
      significantly with the decreasing order of OSTA index (chi2 = 5.432, P = 0.02).
      The OSTA values of <or=-1 and phalanx QUS T-score of <or=-1.95 can differentiate
      postmenopausal nonvertebral fracture with sensitivity of 75% and 81%,
      respectively, and specificity of 48% and 40%, respectively. Combining OSTA and
      phalanx QUS yielded a sensitivity of 83% and a specificity of 84% to detect
      postmenopausal nonvertebral fracture, with an AUC of 0.64. We conclude that OSTA
      and phalanx QUS are simple and effective clinical tools for identifying
      postmenopausal women at increased risk of nonvertebral fractures and can thereby
      facilitate the appropriate and more cost-effective use of bone densitometry to
      prevent osteoporotic fractures in developing countries.

PMID- 18095066
TI  - Associations between osteoprotegerin and femoral neck BMD in hemodialysis
      patients.
AB  - Numerous humoral factors are involved in the development of renal osteodystrophy,
      causing perturbations in bone mineral density (BMD) in patients with end-stage
      renal disease (ESRD). The RANKL/OPG cytokine system appears to mediate the
      effects of many of these factors on bone turnover, contributing to the
      pathogenesis of renal bone disease. The aim of this study was to evaluate the
      clinical and biochemical correlations of BMD measurements in patients on chronic
      hemodialysis. Fifty-four hemodialysis patients underwent measurement of BMD at
      the proximal femur and the lumbar spine (L2-L4). Intact parathyroid hormone
      (PTH), osteoprotegerin (OPG), sRANKL, and main bone biochemical markers were also
      measured in serum samples of all patients. BMD of the femoral neck was negatively
      correlated with OPG levels (r = 0.333, P = 0.014). OPG levels were significantly
      different among normal, osteopenic, and osteoporotic tertiles defined according
      to BMD of the femoral neck. The highest OPG levels were measured in the lowest T
      score (osteoporotic) tertile and were higher than in the osteopenic and normal
      tertiles (P < 0.05). A threshold level for OPG at 21.5 pmol/l enabled the
      detection of osteoporotic patients with 76.5% sensitivity and 62.2% specificity.
      BMD values of trabecular bone-rich sites of the skeleton such as lumbar spine (L2
      L4), trochanter, and Ward' s triangle were inversely correlated with total ALP
      levels (P < 0.05). Hemodialysis patients with low BMD of the femoral neck
      demonstrated higher OPG levels than patients with normal BMD. Those with lumbar
      spine (L2-L4), trochanteric, and Ward's triangle BMDs below the normal range
      presented higher total ALP levels. These results suggest that OPG and total ALP
      may be clinically useful markers in the detection of significant femoral neck and
      trabecular bone mineral deficit in hemodialysis patients, warranting further
      investigations.

PMID- 18095067
TI  - Bone mineral density in prepubertal obese and control children: relation to body
      weight, lean mass, and fat mass.
AB  - The aim of the study was to determine the influence of obesity on bone status in
      prepubertal children. This study included 20 obese prepubertal children (10.7 +/-
      1.2 years old) and 23 maturation-matched controls (10.9 +/- 1.1 years old). Bone
      mineral area, bone mineral content (BMC), bone mineral density (BMD), and
      calculation of bone mineral apparent density (BMAD) at the whole body and lumbar
      spine (L1-L4) and body composition (lean mass and fat mass) were assessed by DXA.
      Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at the calcaneus
      were measured with a BUA imaging device. Expressed as crude values, DXA
      measurements of BMD at all bone sites and BUA (69.30 versus 59.63 dB/MHz, P <
      0.01) were higher in obese children. After adjustment for body weight and lean
      mass, obese children displayed lower values of whole-body BMD (0.88 versus 0.96
      g/cm2, P < 0.05) and BMC (1190.98 versus 1510.24 g, P < 0.01) in comparison to
      controls. When results were adjusted for fat mass, there was no statistical
      difference between obese and control children for DXA and ultrasound results.
      Moreover, whole-body BMAD was lower (0.086 versus 0.099 g/cm3, P < 0.0001),
      whereas lumbar spine BMAD was greater (0.117 versus 0.100 g/cm3, P < 0.001) in
      obese children. Thus, it was observed that, in obese children, cortical and
      trabecular bone displayed different adaptation patterns to their higher body
      weight. Cortical bone seems to enhance both size and BMC and trabecular bone to
      enhance BMC. Finally, considering total body weight and lean mass of obese
      children, these skeletal responses were not sufficient to compensate for the
      excess load on the whole body.

PMID- 18095068
TI  - Low plasma phylloquinone concentration is associated with high incidence of
      vertebral fracture in Japanese women.
AB  - It has been reported that vitamin K supplementation effectively prevents
      fractures and sustains bone mineral density in osteoporosis. However, there are
      only limited reported data concerning the association between vitamin K
      nutritional status and bone mineral density (BMD) or fractures in Japan. The
      objectives were to evaluate the association between plasma phylloquinone (K1) or
      menaquinone (MK-4 and MK-7) concentration and BMD or fracture in Japanese women
      prospectively. A total of 379 healthy women aged 30-88 years (mean age, 63.0
      years) were consecutively enrolled. Plasma K1, MK-4, MK-7, and serum
      undercarboxylated osteocalcin (ucOC) concentrations, BMD, and incidence of
      vertebral fractures were evaluated. In stepwise multiple linear regression
      analyses, L2-4 BMD and a bone turnover marker, log K1, concentrations were
      independently correlated with vertebral fracture incidence. When subjects were
      divided into low and high K1 groups by plasma K1 concentration, the incidence of
      vertebral fracture in the low K1 group (14.4%) was significantly higher than that
      in the high K1 group (4.2%), and its age-adjusted RR was 3.58 (95% CI, 3.26
      3.93). L2-4 BMD was not different between the two groups. These results suggest
      that subjects with vitamin K1 insufficiency in bone have increased susceptibility
      for vertebral fracture independently from BMD.

PMID- 18095069
TI  - Association between vitamin D and bone mineral density in Iranian postmenopausal
      women.
AB  - The role of vitamin-D in determining bone mineral density (BMD), especially in
      less severe vitamin D deficiency, is still unclear. To investigate the possible
      association between 25-hydroxyvitamin D [25(OH)D] and BMD, 245 healthy free
      living postmenopausal women, aged between 40 and 80, were randomly selected from
      participants of a population-based study. BMD was measured at the lumbar spine
      and hip by dual X-ray absorptiometry (Lunar DPXMD 7164). Serum 25(OH)D,
      parathyroid hormone (PTH), calcium, phosphorus, total and bone alkaline
      phosphatases, and urine deoxypyridinoline were measured. PTH was logarithmically
      transformed (LnPTH). Linear regression models were developed to determine the
      association between serum 25(OH)D and BMD at different sites. Means of age and
      duration of menopause were 57.7 +/- 7 and 9.4 +/- 6.8 years, respectively. Mean
      25(OH)D was 73.0 +/- 62.3 nmol/l; 5.3% (n = 13) had 25(OH)D < 25 nmol/l and 37.6%
      (n = 92) had 25(OH)D between 25 and 50 nmol/l. Eleven percent of the women (n =
      27) were osteoporotic in femoral neck and 25.3% of them (n = 62) were
      osteoporotic in lumbar spine sites. 25(OH)D correlated inversely with LnPTH (r = 
      0.25, P < 0.01). In the multivariate analyses, no association was found between
      25(OH)D and BMD at any of the skeletal sites after adjusting for age, duration of
      menopause, body mass index, calcium, and LnPTH. However, BMD was associated
      inversely with LnPTH only in femoral neck but not in the other sites. This study
      did not show any association between 25(OH)D and BMD in free-living Iranian
      postmenopausal women.

PMID- 18095070
TI  - Nonenzymatic collagen cross-links induced by glycoxidation (pentosidine) predicts
      vertebral fractures.
AB  - Advanced glycation end products (AGE) in collagen have been reported to decrease
      the mechanical property of bone. However, there are no available data on the
      relation between fracture risk and levels of glycoxidative (nonenzymatic) cross
      links of collagen in clinical samples. A total of 432 Japanese elderly women who
      were not receiving any drug treatment for osteoporosis were selected and followed
      for 5.2 +/- 3.3 (mean +/- SD) years for this observational study. Vertebral
      fractures and bone mineral density were assessed at baseline and then at 1- to 2
      year intervals or at indication of any symptom. Two types of collagen metabolites
      were measured at baseline: urinary N-terminal telopeptide of type I collagen
      (NTX), a marker of pyridinium cross-link, and urinary pentosidine, a nonenzymatic
      collagen cross-link produced by AGEs. A total of 97 incident vertebral fractures
      on 72 subjects were observed. Simple regression analysis using Cox's hazards
      model showed that log-transformed urinary NTX and pentosidine are significant
      risk factors for time-dependent incidence of vertebral fractures, in addition to
      the traditional risk factors (age, lumbar bone mineral density, and number of
      prevalent vertebral fractures). However, urinary excretion of pentosidine (hazard
      ratio, 1.33; 95% CI, 1.01-1.76, P = 0.04) was a significant predictor of incident
      vertebral fracture after adjustment for other traditional risk factors. The
      present data suggest that AGE-related collagen cross-link is a novel risk for
      vertebral fracture.

PMID- 18095071
TI  - Effect of sports activity on bone mineral density in wheelchair athletes.
AB  - The present study carried out a measurement of body composition and a nutrition
      survey, targeting 28 male wheelchair athletes and comparing them with 25 male
      physically able healthy athletes as the controls. The DXA method was used to
      measure bone mineral density (BMD), percentage of body fat (% body fat), and lean
      body mass (LBM). Possible factors affecting the BMD of the wheelchair athletes
      with spinal injuries were analyzed including age, body part, type of sport, area
      of injury, length of injury, and the length of time it took before restarting
      sports activity after injury. BMD in the arms, body trunk, legs, and entire body
      was measured. There were no significant differences in the BMD of the wheelchair
      athletes by age group (from 20 to 29, from 30 to 39, and 40 years and older), by
      sports (basketball, track and field, and tennis), and by area of injury (high and
      low paraplegia). BMD in the legs (r = -0.549, P < 0.01), body trunk (r = -0.414,
      P < 0.05), and entire body (r = -0.452, P < 0.05) of the wheelchair athletes was
      negatively correlated with the period since injury; however, no such a
      relationship was observed in the arms. In addition, the multiple regression
      analysis for BMD of each body region showed that the earlier the wheelchair
      athletes restarted sports after injury, the higher values the BMD of legs (r = 
      0.467, P < 0.05), body trunk (r = -0.469, P < 0.05), and entire body (r = -0.488,
      P < 0.05), independent of age and sports. The leg BMD of the wheelchair athletes
      was lower than that of the physically able athletes, with a BMD 76.5% of the
      controls. The present study suggests that restarting sports activity in a timely
      manner after treatment and rehabilitation for the injury is useful in preventing
      loss of BMD in wheelchair athletes and ultimately improving their quality of
      life.

PMID- 18095072
TI  - A significant improvement in lower limb pain after treatment with alendronate in
      two cases of Camurati-Engelmann disease.

PMID- 18095073
TI  - Usefulness of a quick decalcification of bone sections embedded in methyl
      methacrylate[corrected]: an improved method for immunohistochemistry.
AB  - Immunohistochemistry of undecalcified bone sections embedded in methyl
      methacrylate (MMA) is not commonly employed because of potential destruction of
      tissue antigenicity by highly exothermic polymerization. The aim of the present
      study was to describe a new technique in which a quick decalcification of bone
      sections embedded in MMA improves the results for immunohistochemistry. The
      quality of interleukin 1alpha (IL-1alpha) immunostaining according to the present
      method was better than the conventional one. Immunostaining for osteoprotegerin
      (OPG) and the receptor activator of NF-kappaB ligand (RANKL) in bone sections of
      chronic kidney disease patients with mineral bone disorders (CKD-MBD) was
      stronger than in controls (postmortem healthy subjects). The present study
      suggested that this method is easy, fast, and effective to perform both
      histomorphometry and immunohistochemistry in the same bone fragment, yielding new
      insights into pathophysiological aspects and therapeutic approaches in bone
      disease.

PMID- 18095074
TI  - Genetic detection of free cancer cells in the peritoneal cavity of the patient
      with gastric cancer: present status and future perspectives.
AB  - The purpose of this review is to examine the current status and future
      perspectives of the molecular analysis of peritoneal lavage fluid in patients
      with gastric cancer. During the past 10 years, the polymerase chain reaction
      (PCR) has been applied for the molecular detection of free cancer cells in the
      abdominal cavity of patients with gastric cancer, and its clinical significance
      in establishing the presence of peritoneal dissemination has been assessed by
      several groups especially in Japan. The majority of these studies have confirmed
      the predictive value of the molecular detection of peritoneal metastasis and
      recurrence using peritoneal lavage fluid. Based on these findings, since April
      2006, the genetic diagnosis of body fluids has been included in the Japanese
      Government public health insurance program for patients with solid tumors.
      However, there are still many obstacles to overcome before the genetic diagnosis
      of micrometastasis can be considered a routine laboratory assay. Here we review
      the importance of the molecular detection of cancer cells in the abdominal
      cavity, and the molecular techniques used for such diagnosis; we also provide
      some clinical examples to illustrate the value of molecular diagnosis.

PMID- 18095075
TI  - Surgeons' knowledge of quality indicators for gastric cancer surgery.
AB  - BACKGROUND: Gastric cancer survival in the West is inferior to that achieved in
      Asian centers. While differences in tumor biology may play a role, poor quality
      surgery likely contributes to understaging. We hypothesize that the majority of
      surgeons performing gastric cancer surgery in North America are unaware of the
      recommended standards. METHODS: Using the Ontario College of Physicians and
      Surgeons registry, surgeons who potentially included gastric cancer surgery in
      their scope of practice were identified. A questionnaire was mailed to 559; of
      those, 206 surgeons reported managing gastric cancer. Results were evaluated by
      chi(2) and logistic regression; P < 0.05 was considered significant. RESULTS:
      Eighty-six percent of respondents were male and 53% practiced in an urban
      nonacademic setting. Forty percent reported operating on two to five cases of
      gastric cancer per year, and 42% on fewer than two cases per year. One-third of
      surgeons identified 4 cm or less to be the desired gross proximal margin. Half
      used frozen section to evaluate margin status. Twenty percent of surgeons were
      unsure of the number of lymph nodes (LN) needed to accurately stage gastric
      cancer, and the median number reported by the remainder was 10 (range, 0-30).
      Only 16 of 206 identified both a proximal margin of 5 cm or less and 15 or more
      LN as desired targets. Those performing more than five gastric resections per
      year were more likely to report a D2 resection (P = 0.008). CONCLUSION: The
      majority of surgeons operating on gastric cancer in Ontario did not identify
      recommended quality indicators of gastric cancer surgery. A continuing medical
      education program should be designed to address this knowledge gap to improve the
      quality of surgery and patient outcomes.

PMID- 18095076
TI  - Experience of surgical morbidity after palliative surgery in patients with
      gastric carcinoma.
AB  - BACKGROUND: Indications for palliative surgery in gastric carcinoma (GC) are
      controversial. Our aim was to describe the results of palliative surgery in GC in
      terms of operative morbidity and survival. METHODS: We conducted a retrospective
      cohort study of patients with GC, who were divided into three groups: resection
      with microscopic residual disease (R1), palliative resection with macroscopic
      residual disease (R2), and gastrojejunostomy. Comparisons were tested with
      analysis of variance (ANOVA) or chi(2) test, and the Kaplan-Meier method was used
      for survival analysis. RESULTS: One hundred and thirty-two patients were included
      in the study: 21 had R1, 71 had R2, and 40 had gastrojejunostomy. Surgical
      morbidity was recorded in 4 patients (19%), 23 patients (32.4%), and 1 patient
      (2.5%) in each of the three groups, respectively (P = 0.001). Operative mortality
      occurred in 6 patients (8.5%) from the R2 group and in 1 (2.5%) patient from the
      gastrojejunostomy group (P = 0.406). Median survivals of the R1, R2, and
      gastrojejunostomy groups were 22.8 months (95% confidence interval [CI], 16.4
      29.3), 12.4 (95% CI, 9.01-15.8) months, and 6.4 months (95% CI, 0-14.6),
      respectively (P = 0.078) CONCLUSION: R1 resections and gastrojejunostomy were
      associated with low surgical morbidity and mortality, unlike R2 resection; in
      this group, surgical morbidity and mortality was high. Therefore, the benefit of
      palliative resection in the presence of extensive residual disease should be
      balanced against the risk of surgical morbidity.

PMID- 18095077
TI  - The predictive value of 18F-FDG-PET early evaluation in patients with metastatic
      gastric adenocarcinoma treated with chemotherapy plus cetuximab.
AB  - BACKGROUND: The aim of the study was to evaluate whether the therapy-induced
      reduction of the (18)F-fluorodeoxyglucose positron emission tomography (18F-FDG
      PET) maximum standardized uptake value in patients with advanced gastric
      adenocarcinoma treated with chemotherapy plus cetuximab could predict the
      objective response and outcome early during the treatment. METHODS: The study was
      performed as a part of a phase II trial evaluating cetuximab plus the
      leucovorin/5-fluorouracil/irinotecan (FOLFIRI) regimen. The objective response
      was evaluated according to the response evaluation criteria in solid tumors
      (RECIST) every 6 weeks. The early metabolic response evaluated by 18F-FDG-PET was
      assessed according to our own evaluated cutoff value (<35%) after receiver
      operating characteristic (ROC) analysis. RESULTS: Twenty of 22 patients had
      positive baseline 18F-FDG-PET. The best RECIST response was: complete response
      (CR), 3; partial response (PR), 9; stable disease (SD), 8. Twelve patients (60%)
      were classified as metabolic responders and 8 (40%) as nonresponders. At the
      median follow-up time of 11 months, median time to disease progression (TTP) and
      overall survival (OS) for early metabolic responders versus nonresponders were 11
      versus 5 months (P = 0.0016) and 16 versus 6 months (P = 0.1493), respectively.
      CONCLUSION: The early metabolic response evaluated by 18F-FDG-PET predicted the
      clinical outcome in this series of patients with advanced gastric cancer treated
      with chemotherapy plus cetuximab.

PMID- 18095078
TI  - Changes in vitamin D after gastrectomy.
AB  - BACKGROUND: We previously reported that the administration of 1alpha hydroxy
      vitamin D3 was effective for treating post-gastrectomy bone disorders.
      Accordingly, we performed the present study to obtain evidence supporting the
      effectiveness of 1alpha hydroxy vitamin D3 in post-gastrectomy patients. METHODS:
      The study involved 22 outpatients who had undergone gastrectomy for gastric
      cancer and had not been treated with 1alpha hydroxy vitamin D3 or calcium. They
      comprised 17 men and 5 women, with a mean age of 61.9 years. Laboratory tests
      were performed to examine the following parameters: 1,25(OH)(2) vitamin D3;
      25(OH) vitamin D3; 24,25(OH)(2) vitamin D3; ionized calcium; calcium; phosphorus;
      alkaline phosphatase; N-parathyroid hormone; and osteocalcin. RESULTS: The level
      of 1,25(OH)(2) vitamin D3, the most active of the vitamin D metabolites, was
      found to be normal in all of the patients. In contrast, the level of 25(OH)
      vitamin D3, which shows weak activity, was below the normal range in 7 of the 22
      patients (31.8%). The mean serum level of 25(OH) vitamin D3 was significantly
      lower in patients at 1 year or more postoperatively than the level in those at
      less than 1 year postoperatively (P = 0.041), as well as being significantly
      lower in patients who had received total gastrectomy than in patients who
      underwent other gastrectomy procedures. The level of 24,25(OH)(2) vitamin D3, a
      metabolite of 25(OH) vitamin D3 that shows weak activity, was below the normal
      range in 19 of the 22 patients (86.4%). On multivariate analyses, factors
      associated with the change in vitamin D metabolites did not remain. CONCLUSION:
      The patients showed a decrease of 25(OH) vitamin D3 and 24,25(OH)(2) vitamin D3,
      which are metabolites that show weak activity. This suggests that a homeostatic
      response maintains the normal level of 1,25(OH)(2) vitamin D3, which is important
      for calcium regulation. Thus, it was suggested that gastrectomy had a moderate
      influence on the metabolism of vitamin D. However we could not detect any factor
      associated with the decrease of 25(OH) vitamin D3 and 24,25(OH)(2) vitamin D3.

PMID- 18095079
TI  - Levels and expressions of orotate phosphoribosyltransferase in gastric carcinoma
      and normal gastric mucosa tissues.
AB  - BACKGROUND: Orotate phosphoribosyltransferase (OPRT; EC 2.4.2.10), a key enzyme
      that catalyzes one of the primary steps in the phosphorylation of
      fluoropyrimidine, was recently recognized as an important enzyme that determines
      the anticancer effects of the dihydropyrimidine dehydrogenase-inhibitory
      fluoropyrimidine, S-1. METHODS: Levels of OPRT were examined in 97 gastric
      carcinoma tissues and 65 normal gastric mucosa tissues obtained from patients
      with gastric carcinoma. The relation between OPRT levels and clinicopathological
      variables was evaluated, and correlations of OPRT with thymidylate synthase and
      dihydropyrimidine dehydrogenase levels in gastric carcinoma tissues were
      evaluated. RESULTS: Although OPRT levels were high in well-differentiated and
      localized carcinomas, they were not correlated with other clinicopathological
      variables or with the pathological stage of gastric carcinoma. Levels of OPRT
      were significantly higher in gastric carcinoma tissue than in normal gastric
      mucosa. OPRT levels were not correlated with levels of either thymidylate
      synthase or dihydropyrimidine dehydrogenase. In samples of gastric carcinoma
      tissues and normal gastric mucosa tissues obtained simultaneously from 24
      patients, no correlation was found between OPRT levels in gastric carcinoma and
      levels in normal gastric mucosa. CONCLUSION: These results suggest that the OPRT
      level is significantly higher in gastric carcinoma tissue than in normal gastric
      mucosa and that the OPRT level in gastric carcinoma is a novel variable that is
      independent of the levels of other previously known enzymes related to 5
      fluorouracil (FU) metabolism.

PMID- 18095080
TI  - Clinicopathological variables associated with lymph node metastasis in submucosal
      invasive gastric cancer.
AB  - BACKGROUND: We aimed to elucidate clinicopathological variables associated with
      lymph node metastasis of submucosal invasive gastric cancer. METHODS: Specimens
      were surgically resected from 201 patients who had primary submucosal gastric
      cancer. We studied 39 consecutive patients with lymph node metastasis and 162
      patients without lymph node metastasis. We compared the following
      clinicopathological characteristics of the patients in relation to lymph node
      metastasis: age, sex, tumor size, histology, extent of submucosal invasion,
      lymphatic and venous invasion, and ulceration of the tumor. Submucosal invasion
      was divided subjectively into sm1, sm2, and sm3 (representing invasion of the
      upper-, middle-, and lower-third of the submucosa, respectively). We also studied
      the relationship between lymph node metastasis of submucosal gastric cancer and
      immunohistochemistry for p53, Ki67, vascular endothelial growth factor (VEGF),
      alpha-fetoprotein, sLe(a), and dendritic cells (DCs). RESULTS: In terms of
      conventional pathological factors, lymph node metastasis in submucosal gastric
      cancer was related to tumor size (P = 0.002), depth of submucosal invasion (P =
      0.001), lymphatic invasion (P < 0.0001), and venous invasion (P = 0.012). Lymph
      node metastasis in sm1 gastric cancer was significantly related to VEGF
      expression (P = 0.047). Also, lymph node metastasis in sm3 gastric cancer was
      significantly correlated with DC expression (P = 0.016). Multivariate analysis
      showed that tumor size, tumor invasion depth in the submucosal layer, and
      lymphatic invasion were independent predictors of nodal metastasis in submucosal
      gastric cancer. CONCLUSION: Conventional pathological factors, such as tumor
      size, depth of submucosal invasion, and lymphatic invasion, have a significant
      influence on lymph node metastasis. VEGF expression and DC expression may be
      helpful predictors of lymph node metastasis in patients with sm1 and sm3 gastric
      cancer, respectively.

PMID- 18095081
TI  - Intraperitoneal administration of paclitaxel and oral S-1 for a patient with
      peritoneal dissemination and hydronephrosis due to advanced gastric cancer.
AB  - We report a patient with type 3 gastric cancer with peritoneal dissemination and
      hydronephrosis who was successfully treated with intraperitoneal infusion of
      paclitaxel and oral administration of S-1. He was diagnosed with unresectable
      gastric cancer with severe peritoneal dissemination by staging laparoscopy. We
      selected combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60
      mg/m(2) was administered intraperitoneally on days 1 and 8, and S-1 at 100
      mg/body was administered orally for 14 days, followed by 7 days' rest, as one
      course. After five courses, primary tumor reduction was confirmed and no cancer
      cells were detected on pathocytological investigation at second-look laparoscopy.
      The patient underwent total gastrectomy with lymph node dissection. He died from
      liver metastasis 29 months after the initial treatment, but he had not suffered
      from peritoneal metastases and had kept a good quality of life (QOL) since that
      treatment. This chemotherapy can be applied as one of the promising candidates
      for the treatment of patients with peritoneal metastasis of gastric cancer.

PMID- 18095082
TI  - Recurrence of gastric cancer in the jejunal pouch after completion gastrectomy.
AB  - We herein present a case of recurrence of gastric cancer in the jejunal pouch
      after total gastrectomy in a 74-year-old man. He had a history of two operations
      for gastric cancer. The second operation was a completion gastrectomy with
      jejunal pouch reconstruction and regional lymphadenectomy, for gastric cancer in
      the cardia of the remnant stomach, performed 2 years and 9 months before the
      present admission. A follow-up endoscopy showed three elevated tumors along the
      suture lines in the jejunal pouch in the upper digestive tract. Resection of the
      jejunal pouch was performed. Gross pathological examination revealed elevated
      lesions along the staple suture lines in the jejunal pouch. Histopathologically,
      moderately differentiated tubular adenocarcinoma involving the muscular layer,
      without lymphatic metastases, was recognized. Recurrence of gastric cancer in the
      jejunal pouch after resection is rare. We suggest that implantation of exfoliated
      cancer cells gave rise to the recurrence of tumors on the suture line in this
      patient. We also review two cases of gastric cancer in the jejunal pouch after
      resection previously described in the literature.

PMID- 18095083
TI  - Suppression of Pseudomonas aeruginosa quorum-sensing systems by macrolides: a
      promising strategy or an oriental mystery?
AB  - A breakthrough in antibiotic chemotherapy for patients with chronic Pseudomonas
      aeruginosa pulmonary infections was brought about by findings in a patient with
      diffuse panbronchiolitis (DPB), who had been treated with erythromycin over a
      period of years. Recent clinical trials have demonstrated that long-term
      macrolide therapy can be used not only for DPB patients but also for those with
      other chronic infections, including patients with cystic fibrosis (CF). The
      pathogenesis of chronic P. aeruginosa infection is considered to arise from a
      bacterial cell-to-cell signaling mechanism, named "quorum-sensing", which enables
      the bacteria to coordinately turn on and off their virulence genes through the
      production of autoinducer molecules. Accumulating evidence from clinical and
      basic science fields suggests the potential of macrolides as Pseudomonas quorum
      sensing inhibitors. In this review, we briefly summarize the data on the clinical
      efficacy of macrolides in DPB and CF patients. Then we discuss the mechanisms of
      action of macrolides from the viewpoint of sub-minimum inhibitory concentration
      (sub-MIC) macrolide effects on P. aeruginosa, particularly the potential activity
      of this antibiotic to suppress the bacterial quorum-sensing system.

PMID- 18095084
TI  - Neutralization of staphylococcal exotoxins in vitro by human-origin intravenous
      immunoglobulin.
AB  - Human-origin intravenous immunoglobulin (IVIG) collected from healthy individuals
      was tested for its neutralizing activity against the hemolysin, toxic shock
      syndrome toxin-1 (TSST-1), and enterotoxins, produced by laboratory strains of
      methicillin-resistant Staphylococcus aureus (MRSA). The hemolytic activity of the
      culture supernatant against sheep red blood cells was reduced from 100% to 5.5%
      relative hemolysis in the presence of 0.156 mg protein/ml of IVIG. The maximum
      dilution endpoint of the culture supernatant for TSST-1-mediated latex
      aggregation was 32-fold. This level of TSST-1 activity was reduced to eightfold
      dilution by 0.78 mg protein/ml of IVIG, and the latex aggregation activity of
      undiluted TSST-1 in the culture supernatant was inhibited by 1.56 mg protein/ml
      of IVIG. Similarly, the enterotoxin A-mediated latex aggregation titer appeared
      to be a 320-fold dilution. This toxin activity was reduced to an 80-fold dilution
      and below a tenfold dilution by 0.049 through 0.78 and 1.56 mg protein/ml,
      respectively, of IVIG. These results show that IVIG has powerful neutralizing
      activity against hemolysin, TSST-1, and enterotoxin A. Therefore, IVIG may be
      useful for passive immunization therapy in patients suffering from diseases
      caused by MRSA exotoxins.

PMID- 18095085
TI  - The effect of griseofulvin on the gene regulation of beta-tubulin in the
      dermatophyte pathogen Trichophyton rubrum.
AB  - Griseofulvin - a mold metabolite produced by Penicillium griseofulvum - is an
      antifungal drug whose interaction with tubulin is poorly understood. In this
      study we cloned the beta-tubulin gene in Trichophyton rubrum, which encodes a
      polypeptide with 447 amino acids (accession number AAV33733). Nucleotide sequence
      comparison in data banks for both the partial DNA and its deduced amino acid
      sequence revealed significant homology with members of the eukaryotic beta
      tubulin gene family. Investigation based on real-time polymerase chain reaction
      (PCR) indicated that griseofulvin treatment of T. rubrum fungal cells decreased
      the expression of the beta-tubulin gene in a dose-dependent manner. However,
      fluconazole had no effect on the beta-tubulin transcript level under the same
      circumstances. The identification of this vital gene, which is potentially
      involved in many cellular functions in pathogenic dermatophyte fungi, is the
      first step towards understanding the functional characteristics of beta-tubulin
      in such fungi and may help in the development of new antifungal drugs against
      dermatophytes.

PMID- 18095086
TI  - Application of an individual-based model with real data for transportation mode
      and location to pandemic influenza.
AB  - Currently, an individual-based model is a basic tool for creating a plan to
      prepare for the outbreak of pandemic influenza. However, even if we can construct
      the model as finely as possible, it cannot mimic the real world precisely.
      Therefore, we should use real data for transportation modes and locations, and
      simulate the diffusion of an infectious disease into that real data. In the
      present study, we obtained data on the transportation modes and locations of 0.88
      million persons a day in the Tokyo metropolitan area. First, we defined the
      location of all individuals in the data set every 6 min. Second, we determined
      how many people they came in contact with in their household, in each area, and
      on the train, and then we assumed that a certain percentage of those contacted
      would become infected and transmit the disease. Data for natural history and
      other parameters were taken from previous research. The average number of
      contacts in each area was 51 748 (95% confidence intervals [CI],46 846-56 650]),
      at home it was 246 (95% CI, 232-260), and on the train it was 91 (95% CI, 81
      101). The number of newly infected people was estimated to be 3032 on day 7 and
      126 951 on day 10. The geographic diffusion on day 7, the day when the earliest
      response would have started, expanded to the whole of the Tokyo metropolitan
      area. We were able to realize the speed and geographic spread of infection with
      the highest reality. Therefore, we can use this model for making preparedness
      plans.

PMID- 18095087
TI  - Substrate specificity of HMRZ-86 for beta-lactamases, including extended-spectrum
      beta-lactamases (ESBLs).
AB  - HMRZ-86 was designed as a new chromogenic cephalosporin to detect extended
      spectrum beta-lactamases (ESBLs) and similar evolved beta-lactamases, such as
      metallo-beta-lactamases, derepressed AmpC, and extended oxacillinase. We report
      here our investigation of the kinetic parameters of several types of beta
      lactamases to show the enzymatic characteristics of HMRZ-86. The Michaelis
      constant (Km values of HMRZ-86 for ESBLs were twice to three and half times as
      high as those of nitrocefin, and the maximum velocity (Vmax) was one-fifth that
      of nitrocefin. The Km and Vmax of HMRZ-86 for AmpC were both smaller than those
      of nitrocefin. The kinetic parameters of HMRZ-86 for metallo beta-lactamase (MBL)
      were very variable, depending on the type of buffer solution used and the
      concentration of zinc ions. For MBL, the Km values of HMRZ-86 were higher than
      those of nitrocefin, but the Vmax values were almost the same as those of
      nitrocefin. Although the chemical structure of HMRZ-86 is similar to that of
      nitrocefin, we think the enzymatic reactivities of the two entities for beta
      lactamases are very different.

PMID- 18095088
TI  - Prevalence of beta-lactamase-nonproducing ampicillin-resistant Haemophilus
      influenzae and Haemophilus influenzae type b strains obtained from children with
      lower respiratory tract infections.
AB  - The prevalence of strains with ampicillin (ABPC) resistance among Haemophilus
      influenzae strains isolated from the nasopharynx of children with lower
      respiratory tract infections has increased significantly during the 6 years from
      2000, when it was 41.9%, to 2005, when it reached 60.1%. From 2002, the
      prevalence exceeded 50%, and the prevalence of beta-lactamase-nonproducing ABPC
      resistant (BLNAR) strains with a minimum inhibitory concentration (MIC) of ABPC
      of over 4 microg/ml doubled, from 28.2% in 2002 to 54.7% in 2005. In H.
      influenzae strains obtained from the nasopharynx of children with lower
      respiratory tract infections between April 2004 and March 2006, identification of
      serotype b was defined, using the slide agglutination method. The frequency of
      isolation of H. influenzae type b (Hib) strains was then measured and the ABPC
      resistance conditions of the Hib strains were also evaluated. The frequency of
      the Hib strains was found to be 30 out of 479 strains, 6.3%. Of these 30 strains,
      BLNAR accounted for 53.3% (16 strains), approximately the same frequency of
      isolation as that of the BLNAR isolated from all H. influenzae strains during the
      same period. In Japan, the prevalence of BLNAR strains among clinically isolated
      H. influenzae strains has continued to increase, and the frequency of isolation
      of BLNAR strains among Hib strains has also continued to rise. As a
      countermeasure, attempts at improving resistance have been made through judicious
      antibiotic use, but concern that the choice of antibiotics for Hib meningitis may
      become complicated has sparked a keen interest in the introduction of Hib
      conjugate vaccine.

PMID- 18095089
TI  - Epidemiology and risk factors for colonization and infection by Acinetobacter
      baumannii in an ICU in Tunisia, where this pathogen is endemic.
AB  - Because Acinetobacter baumannii has become an alarming endemic pathogen in our
      country we decided to conduct this prospective study, from January 2004 to
      December 2005, in order to determine risk factors and outcomes involved in
      clinical colonization or infection by A. baumannii in a 16-bed Tunisian intensive
      care unit (ICU). One hundred and two A. baumannii isolates were obtained from 63
      patients, with an infection rate of 45%. The rate of multidrug-resistant (MDR) A.
      baumannii was 39% during the 2-year study, with an epidemic outbreak in October
      2004. This outbreak was followed by closure of all the involved ICU rooms and the
      selective intestinal decontamination of patients, with polymyxin. During the 12
      month post-intervention program (January-December 2005), the infection rate
      declined. The analysis of risk factors for the spread of A. baumannii showed that
      only the Simplified Acute Physiological Score (SAPS II) was involved. On the
      other hand, no risk factor was identified for multidrug resistance in patients
      either colonized or infected by A. baumannii. There was a statistically
      significant difference only in crude mortality (67.5% in MDR A. baumannii vs
      46.7% in susceptible A. baumannii; P = 0.04).

PMID- 18095090
TI  - Clinical features of immunocompromised and nonimmunocompromised patients with
      pulmonary tuberculosis.
AB  - Although patients with risk factors for tuberculosis have increased with the
      increased use of immunosuppressive therapy, there have been few reports about
      differences in clinical findings between immunocompromised patients and
      nonimmunocompromised patients with pulmonary tuberculosis. Therefore, we
      investigated differences between the clinical features of immunocompromised
      patients with pulmonary tuberculosis and those of nonimmunocompromised patients
      in the past decade. We analyzed findings in 840 patients (312 immunocompromised
      and 528 nonimmunocompromised) with pulmonary tuberculosis who were found to be
      culture-positive for Mycobacterium tuberculosis between January 1997 and December
      2006. The characteristic clinical findings of the immunocompromised patients,
      compared with findings in the nonimmunocompromised group, were as follows: (1) an
      increase in the number of patients with respiratory symptoms during the period of
      follow-up of underlying diseases; (2) an increase in the number of patients in a
      hyponutritional state and with a negative response for the tuberculin skin test;
      (3) an increase in the number of microbiologically smear-positive sputum
      specimens; (4) an increase in the number of patients with atypical radiological
      findings, such as a few cavities or calcification, bilateral and expansive
      consolidation, miliary shadows, and mediastinal and/or hilar lymphadenopathy ;
      (5) an increase in the number of patients with misdiagnosed pneumonia at
      admission; and (6) an increase in the mortality rate. We concluded that, among
      the immunocompromised patients with pulmonary tuberculosis, there were many
      patients with atypical radiological findings and with smear-positive findings for
      acid-fast bacilli examination that was carried out to isolate M. tuberculosis
      (which had become infectious). We must perform the acid-fast bacilli examination
      for patients who have a fever and continuous cough, and antituberculous drugs
      should be administered as soon as possible when the results are positive.

PMID- 18095091
TI  - Group A beta-hemolytic streptococcal hemorrhagic colitis complicated with
      pharyngitis and impetigo.
AB  - A 6-year-old boy with bloody diarrhea was diagnosed with group A beta-hemolytic
      streptococcal hemorrhagic colitis. Complications included pharyngitis and
      impetigo, both caused by the same organisms. In addition to being isolated from
      stools, Streptococcus pyogenes was also isolated from skin lesions. Furthermore,
      a rapid group A streptococcal antigen test by throat swab was also positive.
      Hemorrhagic colitis caused by group A beta-hemolytic streptococcus is extremely
      rare, and much rarer are its complications with pharyngitis and impetigo.
      Compared with findings in reports of group A beta-hemolytic streptococcal
      proctitis and perianal and perineal diseases, this case suggests a distinct
      pathogenesis for hemorrhagic colitis.

PMID- 18095092
TI  - An indeterminate QuantiFERON TB-2G response for miliary tuberculosis, due to
      severe pancytopenia.
AB  - We report the case of a 56-year-old man with miliary tuberculosis whose response
      to the QuantiFERON (QFT) TB-2G (Cellestis; South Melbourne, Australia) test was
      indeterminate due to pancytopenia (lymphocytopenia). The patient had severe
      lymphocytopenia due to either the miliary tuberculosis or immunosuppressive
      treatment with a corticosteroid; for the 2 years before admission, he had
      received corticosteroid treatment for Behcet's disease. The lymphocytopenia was
      also a complication of multiple organ failure and disseminated intravascular
      coagulation. A chest radiograph and computed tomography (CT) scan revealed a
      miliary shadow. After intubation performed because of acute respiratory failure,
      Mycobacterium tuberculosis was cultured from bronchoalveolar lavage fluid. We
      made a clinical diagnosis of miliary tuberculosis because M. tuberculosis was
      demonstrated in both lung and bone marrow specimens. However, immunologically,
      the tuberculin skin test was negative and the QFT-TB 2G test response was
      indeterminate, based on the CDC guideline. Although the QFT-TB 2G test has been
      used recently as a supportive method for the diagnosis of active tuberculosis,
      care must be taken in judging the condition of a patient with lymphocytopenia
      caused by severe underlying disease or immunosuppressive treatment. This patient
      was treated with antituberculous drugs 3 days after admission, but he died of
      multiple organ failure 6 days after admission.

PMID- 18095093
TI  - Molecular epidemiology of outbreaks and containment of drug-resistant Pseudomonas
      aeruginosa in a Tokyo hospital.
AB  - We witnessed outbreaks of multidrug-resistant (MDR) and drug-resistant
      Pseudomonas aeruginosa at a hospital in Tokyo, Japan, during the period September
      2004 through May 2005. The first outbreak occurred in September and October 2004.
      Three isolates of MDR P. aeruginosa were identified from urine samples obtained
      from three nonambulatory immunodeficient patients in one ward. After 3 weeks,
      another outbreak of P. aeruginosa occurred in the hematology ward on the same
      floor of the hospital. During the outbreaks, environmental surveys were conducted
      twice in each of the two wards, at 2-week intervals, to identify the sources of
      the pathogens. A total of 23 P. aeruginosa isolates, including 11 from
      environmental sources, were analyzed for chromosomal DNA typing by pulsed-field
      gel electrophoresis, for O-antigen serotyping, and for other typing. Results
      revealed two causative clones, as well as environmental contamination by P.
      aeruginosa clones on the surfaces of urine volume-measuring devices in rooms
      where urine is handled, which may have been sources of the pathogens during the
      outbreaks. To prevent further outbreaks, we performed the following: (a)
      environmental surface monitoring for drug-resistant P. aeruginosa, (b) active
      surveillance of specimens, (c) strict isolation of infected patients or carriers
      of MDR P. aeruginosa, (d) rigorous contact precautions, and (e) disinfection with
      70% alcohol on the surfaces of apparatuses contaminated by MDR or drug-resistant
      P. aeruginosa and in the rooms where urine is handled. As a result, the outbreaks
      were contained.

PMID- 18095094
TI  - Splenic abscess in an infant caused by Streptococcus intermedius.
AB  - We report a 20-month-old girl with splenic abscess. The patient was admitted to
      our hospital because of persistent high fever and abdominal pain. Laboratory data
      showed leucocytosis and elevated C-reactive protein levels. Abdominal computed
      tomography showed multiple low-density lesions in the spleen. These findings were
      consistent with a diagnosis of splenic abscess. She was successfully treated with
      ultrasonographically guided percutaneous drainage for 11 days and intravenous
      antibiotic for 17 days. On culture, aspirated fluid from the abscess grew
      Streptococcus intermedius. This case illustrates that the differential diagnosis
      of unknown-focus infection in infants should include splenic abscess. We
      recommend conservative therapy (antibiotics and drainage) as first-line therapy
      for splenic abscess in pediatric patients, based on the importance of the
      immunological functions of the spleen.

PMID- 18095095
TI  - Elevated serum levels of human matrix metalloproteinase-9 (MMP-9) during the
      induction of peripheral blood stem cell mobilization by granulocyte colony
      stimulating factor (G-CSF).
AB  - To investigate the role of matrix metalloproteinases (MMPs) in the mobilization
      of peripheral blood stem cells stimulated by granulocyte colony-stimulating
      factor (G-CSF), we analyzed MMP serum levels in 11 healthy donors and 9 patients
      who had hematological malignancies or germ cell tumors. A dose of 5-10 microg/kg
      per day of G-CSF (lenograstim) was administered for 4-8 days to each subject. The
      serum levels of MMP-2, and MMP-9; interleukin-3, -6, -8, and -10; stem cell
      factor; interferon-gamma; and tumor necrosis factor-alpha were measured both
      before and during G-CSF administration. MMP-9 was found to be increased in both
      the cancer patients and the healthy donor group. In contrast, the levels of each
      of the other factors tested were unchanged. No significant positive correlation
      was observed between the MMP-9 levels and the number of CD34+ cells. Hence, we
      found no significant role for MMPs during the mobilization of peripheral blood
      stem cells stimulated by G-CSF.

PMID- 18095096
TI  - Recent changes in the trends of seasonal influenza outbreaks in the Nagano
      Prefectural area of Japan: an oseltamivir effect?
AB  - We carried out a study to assess the pharmacological role of oseltamivir in the
      regulation of influenza epidemics in Japan, examining data for the years 1998 to
      2006 from Nagano Prefecture. Oseltamivir is effective for the treatment of
      influenza, and its use in Japan has increased in the 3 years from 2003 to 2006.
      We found that, in the Nagano Prefectural area, the peak in the number of
      influenza infections showed a deviation to later periods after the 2003 season.
      and after 2003, it also took a longer time to reach the end of the seasonal
      epidemics of influenza infections compared with data from 1998 to 2002. To
      prevent influenza outbreaks having a long duration, we believe that the period of
      isolation in patients receiving anti-influenza drugs has to be reconsidered.

PMID- 18095097
TI  - Substance P receptor in U373 MG human astrocytoma cells activates mitogen
      activated protein kinases ERK1/2 through Src.
AB  - Substance P (SP) acting through substance P receptor (SPR) increases the
      proliferation of glioblastoma cells. At the molecular level, stimulation of SPR
      in human U373 MG glioblastoma cells results in phosphorylation of mitogen
      activated protein kinases ERK1/2. Examination of the underlying mechanism reveals
      that SPR mediates ERK1/2 phosphorylation in a calcium-dependent manner.
      Surprisingly, blockade of epidermal growth factor receptor (EGFR), which is
      transactivated by SPR, has a minimal effect on SPR-mediated ERK1/2
      phosphorylation. However, SPR-mediated ERK1/2 phosphorylation is significantly
      reduced by the Src kinase inhibitor PP2. Interestingly, ERK1/2 in U373 MG cells
      is also activated by several other mitogenic G protein-coupled receptors (GPCRs)
      including alpha(1B)-adrenergic, M(3)-muscarinic, and H(1)-histaminergic in an Src
      dependent manner. We conclude that c-Src is a mediator of SP-stimulated ERK1/2
      phosphorylation in human U373 MG glioblastoma cells.

PMID- 18095098
TI  - Pathological features of intracranial germinomas with reference to fibrous tissue
      and granulomatous change.
AB  - Intracranial germinomas are accompanied occasionally by a significant
      granulomatous change and abundant fibrous tissue, and this has made their
      pathological diagnosis difficult. However, the incidence of the granulomatous
      reaction and the presence of fibrous tissue together with their clinical
      characteristics in intracranial germinomas have not been fully investigated.
      Twenty-four germinomas, none of which had received preoperative treatment, were
      clinicopathologically examined. The location of the tumor was the pineal region
      (5 cases), the suprasellar region (13 cases), multiple lesions (2 cases), the
      basal ganglia region (1 case), and other regions (3 cases). Histologically, the
      germinomas could be divided into two types: (1) type A (18 cases) consisted
      mainly of large neoplastic cells and small lymphocytes, showing a two-cell
      pattern; (2) type B (6 cases) consisted predominantly of fibroinflammatory
      tissues containing occasional neoplastic cells (5/6 cases) and, rarely,
      neoplastic cells (1/6 cases). Perioperatively, two-cell-pattern germinomas (type
      A) were characterized as soft tumors and fibroinflammatory germinomas (type B) as
      hard tumors. Thus, the fibroinflammatory type B accounted for 25% of the
      intracranial germinomas. Although there were no topographical and clinical
      differences between the two types, we conclude that immunohistological studies to
      detect neoplastic germ cells are warranted in cases of small stereotactic
      biopsies of hard type B tumors.

PMID- 18095099
TI  - Paraganglioma of cauda equina: report of seven cases.
AB  - The authors report seven uncommon cases of paraganglioma of the cauda equina
      region with reference to their clinical, radiological, and pathological findings.
      The common presenting symptoms in all the patients were low backache with
      radiation to both thighs, sensory and motor deficits in four patients, and
      urinary retention in three patients. One patient presented with ataxia and
      superficial sidrosis of the brain. Magnetic resonance imaging (MRI) revealed well
      circumscribed lesions that were isointense on T1- and T2-weighted images with
      flow voids. All the tumors were well circumscribed and could be excised
      completely; however, one recurred. Histological examination revealed a classic
      "zellballen" pattern in four tumors. Two mimicked ependymoma but were confirmed
      as paraganglioma by immunohistochemistry. MIB-1 LI was low in all the tumors.
      Thus, there were no identifying clinical or radiological features that helped in
      differentiating paraganglioma from other common tumors, such as ependymoma or
      neurinoma, in this region, and preoperative diagnosis was not possible in any of
      the cases. Morphologic features and immunohistochemical analysis proved to be the
      mainstay of arriving at a correct diagnosis. This report highlights the
      significance of important morphologic features and immunohistochemistry in the
      diagnosis of paraganglioma at this unusual site.

PMID- 18095100
TI  - Epithelioid glioblastoma: a case report.
AB  - A 43-year-old woman who had undergone breast cancer surgery 1 year previously
      complained of headache and nausea. Her brain computed tomography (CT) scan and
      magnetic resonance imaging (MRI) showed a well-circumscribed, heterogeneously
      enhanced tumor in the right thalamus. She underwent gross total resection of the
      tumor followed by radiochemotherapy, and her clinical course was uneventful after
      surgery. Histological examination revealed a moderate number of tumor cells with
      fine bipolar processes in a mucoid matrix, which suggested pilocytic astrocytoma.
      The tumor was associated with microvascular proliferation but did not show
      significant mitosis or necrosis. In some areas, it had an epithelioid appearance,
      with ribbon-like, cribriform, and pseudoglandular patterns involving cuboid
      shaped cells showing nuclear atypia and mitotic figures. Immunohistochemically,
      the tumor cells were positive for glial fibrillary acidic protein (GFAP) and
      vimentin in the area resembling pilocytic astrocytoma, but in the epithelioid
      area they were negative for GFAP and vimentin as well as for breast cancer
      markers, including AE1/AE3. The proliferating potential, represented by the MIB-1
      labeling index, was high (82.5%) in the area of epithelioid appearance, compared
      to only 3% in the area of pilocytic astrocytoma-like appearance. As a rare
      histoarchitectural variant of glioblastoma, the epithelioid pattern may represent
      a very primitive tumor cell phenotype. Typically, this pattern is characterized
      by well-circumscribed masses, although its clinical significance is unknown.

PMID- 18095101
TI  - A case of cervicomedullary junction tanycytic ependymoma associated with marked
      cyst formation.
AB  - Tanycytic ependymomas are a subtype of ependymomas that were formally recognized
      as a new pathological entity in the latest World Health Organization (WHO)
      classification of 2000. They occur mostly in the spinal cord. Only a few reports
      have analyzed the proliferative potentials of these tumors; however, it has been
      reported that the MIB-1 labeling index of tanycytic ependymoma is lower than that
      of other subtypes of WHO grade II ependymomas. We report a rare case of
      cervicomedullary junction tanycytic ependymoma associated with marked cyst
      formation. A 62-year-old man had a history of progressive gait disturbance,
      diplopia, and swallowing disturbance over a one-month period prior to admission.
      Magnetic resonance imaging (MRI) showed a cystic mass with a mural nodule at the
      cervicomedullary junction with Gd-DTPA enhancement. Cyst-subarachnoid shunt was
      performed using a far lateral approach. After 6 years, however, the man was
      readmitted to the hospital because of reaccumulation of the cyst. Partial removal
      of a mural nodule and a cyst-subarachnoid shunt were performed simultaneously by
      a midline suboccipital approach. The pathological diagnosis was tanycytic
      ependymoma. Postoperatively, the patient recovered well and was discharged from
      the hospital without further treatment. Most of the tumor cells had small, round
      nuclei; pleomorphism was minimal. The cytoplasm was dilated. The tumor cells were
      positive for EMA and s-100, and negative for CD-34. GFAP was not determined due
      to difficulty caused by background glial processes. The MIB-1 labeling index was
      less than 1%. Ultrastructurally, the tumor cells had ependymal cell features,
      such as desmosomes and microvilli. Based on these findings, the pathological
      diagnosis was tanycytic ependymoma.

PMID- 18095102
TI  - A nonspecific form of dysembryoplastic neuroepithelial tumor presenting with
      intractable epilepsy.
AB  - We report here an intractable epilepsy case with fairly typical
      clinicoradiological features of dysembryoplastic neuroepithelial tumor (DNT),
      which means onset of seizures at a young age accompanying a medial temporal
      cystic lesion enclosed in cortical dysplasia (CD). The medial cystic lesion was
      composed of two morphologically distinct components; one was oligo-like and the
      other showed some tendency toward neuronal and glial differentiation, even though
      they were morphologically different from a so-called specific glioneural element
      (SGE). Epileptiform discharges were detected not only on the medial lesion but
      also on the lateral inferior temporal gyrus, which was confirmed as CD. According
      to both histopathological and clinical features, we named the lesion a
      nonspecific form of DNT.

PMID- 18095103
TI  - A case of petrous bone myxoid chondrosarcoma associated with cerebellar
      hemorrhage.
AB  - We report a rare case in which a myxoid chondrosarcoma originated from the
      petrous bone and invaded the cerebellar hemisphere with hemorrhage. Neuroimaging
      showed the characteristic feature of multiple small cysts along the solid tumor,
      and the cystic formation was confirmed as a mucoid secretion by Alcian blue
      staining and electron microscopic examination. This tumor recurred following
      partial removal and stereotaxic radiosurgery.

PMID- 18095104
TI  - Basal ganglion hamartoma in a patient presenting with precocious puberty.
AB  - We report a basal ganglion hamartoma in a 10-year-old boy in whom the major
      clinical feature was precocious puberty. Endocrinological evaluation showed a
      gonadotropin reaction to luteinizing hormone-releasing hormone with no elevation
      of the human chorionic gonadotropin beta-subunit level in the serum or
      cerebrospinal fluid. Neuroimaging studies showed a small, calcified, nonenhanced
      mass lesion with some cystic components in the right basal ganglion.
      Histopathological examination of specimens removed by stereotactic needle biopsy
      revealed disorganized neuronal and glial elements in the calcified gray matter
      like lesion. In addition, although the presence of microcalcifications was not
      conspicuous, similar neuroglial lesions of various sizes were scattered in the
      surrounding white matter. Immunostaining for Ki-67 antigen (MIB-1) showed very
      low proliferative potential of the glial cells in all the lesions. To our
      knowledge, this is the first reported occurrence of an intracranial hamartoma
      located in a site other than the hypothalamus and causing precocious puberty. The
      possible mechanisms underlying the development of precocious puberty in this
      patient are discussed.

PMID- 18095105
TI  - Re: angiogenesis and antiangiogenic therapy for malignant gliomas.

PMID- 18095106
TI  - Microscopic anatomy of the brain-meningioma interface.
AB  - We analyzed the relation between meningioma and the brain in 50 surgical cases.
      So-called capsule formation was seen in 20 meningiomas, of which 13 were
      categorized as thin and 7 as thick. In 21 meningiomas the arachnoid membrane was
      intact, and 10 meningiomas had no underlying arachnoid membrane. The other 19
      tumors showed partial disruption of the arachnoid membrane. The degree of
      arachnoid disruption correlated with the tumor grade, perifocal edema, pial blood
      supply on angiography, and tumor size. The existence of brain invasion correlated
      with the tumor grade and partially with tumor size. In case of invasive tumor,
      GFAP-positive cells were found deep in the tumor, usually in contact with blood
      vessels. The axons in gliotic brain often showed degenerative changes such as
      ballooning or varicose swelling. Meningiomas were usually demarcated by a
      basement membrane that was collagen type 4 (Col4)-positive. However, atypical and
      anaplastic meningiomas usually lacked Col4 staining at the interface. In two
      benign meningiomas that looked like an invasive growth, Col4 staining was seen
      above the brain. A pia mater-like structure covered the tumor surface in both
      cases. We could not demonstrate a relation between the expression of matrix
      metalloproteinase (MMP)-2 or MMP-9 and arachnoid disruption or brain invasion.

PMID- 18095107
TI  - Cytological interface of diffusely infiltrating astrocytoma and its marginal
      tissue.
AB  - Cytological differences between infiltrating lesions of the diffusely
      infiltrating astrocytoma (DIA) and reactive gliosis at its periphery have not yet
      been established. We compared histological specimens from cytological crush
      preparations of 200 brain tumors to characterize the cytology of the DIA and to
      discriminate it from reactive gliosis. First, the cytological findings of the
      backgland brain parenchyma were assessed. Second, we looked at the nuclear
      characteristics of the DIA, comparing them with those of other brain tumors.
      Third, the cytology of the infiltrating DIA was assessed together with brain
      parenchymal elements. Finally, we characterized discriminative points of the area
      of infiltration of the DIA versus those of the reactive gliosis. In addition, we
      assessed the relations between the cytological findings of the DIA and its MRI
      images. The cytological findings of this area are important because the surgeon
      may have to make a rapid diagnosis regarding the existence of the tumor.

PMID- 18095108
TI  - Histological findings at the boundary of craniopharyngiomas.
AB  - Although a craniopharyngioma is grossly well circumscribed, microscopically the
      borders are frequently irregular and may be associated with gliosis in the
      adjacent brain tissue. In the current study, we investigated the histology of the
      interface between craniopharyngiomas and surrounding normal structures such as
      the hypothalamus and pituitary gland. Histologically, we classified the findings
      at the boundary of craniopharyngiomas into three types. In type 1, a relatively
      thick capsule-like tissue was identified at the boundary between the
      craniopharyngioma and surrounding normal structure composed of tumor cells and
      inflammatory changes. In type 2, a craniopharyngioma had a relatively clear
      cleavage between the surrounding gliosis. In type 3, the boundary had some
      interdigitation of the tumor in the surrounding gliotic layer adjacent to the
      craniopharyngioma. In types 1 and 3, surgeons may fail to accomplish complete
      resection of the tumor. These histological features may result in recurrence of
      craniopharyngioma even after gross total resection.

PMID- 18095109
TI  - Expression of the constitutively activated RelA/NF-kappaB in human astrocytic
      tumors and the in vitro implication in the regulation of urokinase-type
      plasminogen activator, migration, and invasion.
AB  - Although malignant gliomas are highly invasive tumors, a characteristic that
      contributes to the commonly observed therapeutic failures and local disease
      recurrences, the molecular events that regulate invasion in these tumors remain
      poorly understood. Because the transcription factor RelA/NF-kappaB has been shown
      to regulate invasion during several cellular processes, we have examined
      immunohistochemically expression of the constitutively activated RelA/NF-kappaB
      in tissues obtained from 49 astrocytic tumors [8 diffuse astrocytomas, 9
      anaplastic astrocytomas (AAs) and 32 glioblastomas (GBMs)]. In addition, we
      examined the in vitro effects of antisense oligonucleotides and curcumin on the
      expression and activation of RelA/NF-kappaB, urokinase-type plasminogen activator
      (u-PA) expression, migration, and invasion in the T98G glioma cell line.
      Expression of the constitutively activated RelA/NF-kappaB was observed in 2 (25%)
      of 8 cases of diffuse astrocytomas, 5 (55.6%) of 9 cases of AAs, and 30 (93.8%)
      of 32 cases of GBMs. This expression was significantly correlated with the
      malignant potential in astrocytic tumors (P < 0.001). Moreover, antisense
      oligonucleotides and curcumin inhibited phorbol-12-myristate-13-acetate (PMA)
      induced RelA/NF-kappaB expression or activation (or both), down-regulated u-PA
      expression, and reduced the migration and invasive potentials of T98G glioma
      cells. Thus, the expression of constitutively activated RelA/NF-kappaB is
      associated with malignancy potential in astrocytic tumors and may play a critical
      role in the regulation of u-PA expression and invasiveness in gliomas. RelA/NF
      kappaB may therefore be an intriguing candidate for studies aimed at
      understanding and prevention of the invasiveness of gliomas.

PMID- 18095110
TI  - High expression of L-type amino acid transporter 1 in infiltrating glioma cells.
AB  - L-type amino acid transporter 1 (LAT1), a neutral amino acid transport agent, is
      essential for the transport of large neutral amino acids. LAT1 also corresponds
      to tumor-associated gene-1 (TA1), an oncofetal antigen that is expressed
      primarily in fetal tissues and cancer cells such as glioma cells. We have
      investigated the expression of the transporter in the human primary glioma tissue
      from 68 patients. Among these patients, we could see the border zone between
      tumors and normal bain tissues in 10 patients. By WHO criteria, two of the
      specimens were diagnosed as grade 2, three as grade 3, and five as grade 4
      [glioblastoma multiforme (GBM)]. In 9 of 10 cases, we could identify the
      infiltrating glioma cells associated with stronger immunoreactivity for LAT1.
      These tumor cells aggregated around the neurons in the border zone and were often
      found in the perivascular space. In one GBM case, the tumors seemed to develop
      expansively and separated from the normal brain with a border of arachnoid
      membrane. The expression of LAT1 was always higher in infiltrating glioma cells
      than in cells located in the center of the tumor. These findings suggest that
      LAT1 is one of the molecular targets for glioma therapy.

PMID- 18095111
TI  - Treatment of refractory seizures due to a benign mass present in the corpus
      callosum with an ion magnetic inductor: case report.
AB  - A 39-year-old female patient was having episodes of body stiffness that affected
      her motor abilities. A lipoma in the corpus callosum was identified by computed
      tomography. Her condition deteriorated rapidly, and seizures were refractory to
      any treatment. Seizure frequency and severity increased, incapacitating the
      patient completely. When seizure control was not achieved by any other treatment,
      the patient decided to undergo experimental therapy with the ion magnetic
      inductor. Treatment with the ion magnetic inductor notably reduced the seizure
      frequency and intensity. After treatment the patient was able to return to work
      and other normal activities. The long-term effects are not yet known, but there
      have been no adverse events to date. The patient is still undergoing ion magnetic
      inductor treatment daily in the same way other epileptic patients must continue
      with the use of antiepileptic drugs for life. There is evidence in the literature
      that other types of electromagnetic therapy, such as repetitive transcranial
      magnetic stimulation (rTMS), may be useful for treating refractory seizures. The
      potential advantage of the ion magnetic inductor over rTMS is that there is no
      need to locate precisely the epileptogenic focus, making the treatment procedure
      simpler and faster.

PMID- 18095112
TI  - Analyses of the mechanism of intracellular transport and secretion of pituitary
      hormone, with an insight of the subcellular localization of pituitary hormone and
      its mRNA.
AB  - Combined in situ hybridization (ISH) and immunohistochemistry (IHC) under
      electron microscopy (EM-ISH&IHC) has sufficient ultrastructural resolution and
      provides two-dimensional images of subcellular localization of pituitary hormone
      and its mRNA in a pituitary cell. The advantages of semiconductor nanocrystals
      (Quantum dots, Qdots) and confocal laser scanning microscopy (CLSM) enable us to
      obtain three-dimensional images of subcellular localization of pituitary hormone
      and its mRNA. Both EM-ISH&IHC and ISH&IHC using Qdots and CLSM are useful for
      understanding the relation between protein and mRNA simultaneously in two or
      three dimensions. Another important issue is the intracellular transport and
      secretion of pituitary hormone. We have developed an experimental pituitary cell
      line, the GH3 cell, which has growth hormone (GH) linked to enhanced yellow
      fluorescein protein (EYFP). This stable GH3 cell secretes GH linked to EYFP upon
      stimulated by Ca2+ influx or Ca2+ release from storage. This GH3 cell is useful
      for real-time visualization of the intracellular transport and secretion of GH.
      These three methods enable us to visualize consecutively the process of
      transcription, translation, transport, and secretion of pituitary hormone.

PMID- 18095113
TI  - Mutational analysis of transforming growth factor-beta receptor type II and Smad3
      tumor suppressor genes in prolactinomas.
AB  - The presence of transforming growth factor-beta receptor type II and Smad3 gene
      abnormality was examined in human prolactinomas by single-strand conformation
      polymorphism screening for gene abnormality and band shift in tumor tissue and
      peripheral blood samples obtained from 14 patients treated for prolactinoma.
      Direct sequencing of exon 4 of the transforming growth factor-beta receptor type
      II gene, which showed a band shift by single-strand conformation polymorphism,
      disclosed a single nucleotide polymorphism (rs2228048) (alleles A/G; average
      allele frequency, G:0.817, A:0.183) and not an active mutation. Seven of the 14
      cases showed base substitution (G --> A) of the single nucleotide polymorphism.
      Two of these 7 cases showed base substitution (G --> A) in the blood sample in
      accordance with neoplastic transformation. Direct sequencing of exon 2 of the
      Smad3 gene, which showed band shift by single-strand conformation polymorphism,
      disclosed single nucleotide polymorphism (rs1065080) (alleles C/T; average allele
      frequency, C:0.947, T:0.053) and no active mutation. Four of the 14 cases showed
      base substitution (C --> T) of the single nucleotide polymorphism. Blood samples
      were available for 2 of these 4 cases, and 1 of these 2 cases showed base
      substitution (C --> T) in accordance with neoplastic transformation. Estimation
      of the drug sensitivity of pituitary adenoma based on analysis of peripheral
      blood cells needs special care.

PMID- 18095114
TI  - Dural invasion of meningioma: a histological and immunohistochemical study.
AB  - Meningioma usually grows and expands into the brain, but invasion into the brain
      parenchyma is relatively rare. Meningioma arises from arachnoid cap cells, and
      infiltration into dura mater is the main growth pattern of meningiomas. However,
      little is known about the mechanism of meningioma invasion into the dura mater.
      In this study, seven specimens, including dural attachments, from seven cases of
      meningioma were used for immunohistochemical analysis. Matrix metalloproteinase
      (MMP)-1, -2, -9, urokinase-type plasminogen activator (uPA), vascular endothelial
      growth factors (VEGF), flt-1, E-cadherin, estrogen receptor (EgR), progesterone
      receptor (PgR), and aquaporin (AQP)-1, -4 were used as primary antibodies. There
      were several patterns of meningioma invasion into the dura mater: papillary
      shaped invasion with destruction of dural structure, infiltration along the
      fibers of the dura mater, and invasion of several tumor cell units with
      fibroblast infiltration. Strong immunostaining was obtained with MMP-1, followed
      by AQP-1 and uPA, within the invading tumor cells. Neovasculature and
      extravasated erythrocytes, which stained with AQP-1, were also occasionally
      observed around the invading tumor cells. Simpson grade II removal of meningiomas
      results in high recurrence rates, and the inhibition of meningioma growth via
      dural invasion will facilitate improved remission in many cases with meningioma.
      In this study, MMP-1, AQP-1, and uPA are considered to have some role in the
      dural infiltration of meningioma cells. The fact that AQP-1 was highly expressed
      at the dural attachment and invading front of meningioma may indicate that dural
      invasion of the meningioma may be facilitated by AQP-1-induced water flow and
      neovascularization.

PMID- 18095115
TI  - Multivoxel proton MRS for differentiation of radiation-induced necrosis and tumor
      recurrence after gamma knife radiosurgery for brain metastases.
AB  - Multivoxel proton magnetic resonance spectroscopy (MRS) was used for
      differentiation of radiation-induced necrosis and tumor recurrence after gamma
      knife radiosurgery for intracranial metastases in 33 consecutive cases. All
      patients presented with enlargement of the treated lesion, increase of
      perilesional brain edema, and aggravation or appearance of neurological signs and
      symptoms on average 9.3 +/- 4.9 months after primary treatment. Metabolic imaging
      defined four types of lesions: pure tumor recurrence (11 cases), partial tumor
      recurrence (11 cases), radiation-induced tumor necrosis (10 cases), and radiation
      induced necrosis of the peritumoral brain (1 case). In 1 patient, radiation
      induced tumor necrosis was diagnosed 9 months after radiosurgery; however,
      partial tumor recurrence was identified 6 months later. With the exception of
      midline shift, which was found to be more typical for radiation-induced necrosis
      (P < 0.01), no one clinical, radiologic, or radiosurgical parameter either at the
      time of primary treatment or at the time of deterioration showed a statistically
      significant association with the type of the lesion. Proton MRS-based diagnosis
      was confirmed histologically in all surgically treated patients (7 cases) and
      corresponded well to the clinical course in others. In conclusion, multivoxel
      proton MRS is an effective diagnostic modality for identification of radiation
      induced necrosis and tumor recurrence that can be used for monitoring of
      metabolic changes in intracranial neoplasms after radiosurgical treatment. It can
      be also helpful for differentiation of radiation-induced necrosis of the tumor
      and that of the peritumoral brain, which may have important clinical and
      medicolegal implications.

PMID- 18095116
TI  - Pathological and clinical features of cystic and noncystic glioblastomas.
AB  - The aim of this study is to review the different histological and clinical
      characteristics of glioblastoma multiforme (GBM) with and without cysts (cystic
      and noncystic GBM, respectively). Thirty-seven GBM were collected; these were
      tumors for which more than 80% of the volume was surgically resected, including a
      portion of the peripheral parenchyma of the brain. Based on preoperative magnetic
      resonance (MR) imaging studies, tumors were tentatively classified as cystic GBM
      if more than 50% of their volume appeared to be liquid; otherwise, they were
      considered to be noncystic GBM. Tumor volumes were estimated from contrast
      enhanced T1-weighted MR images. Edema was deduced from the maximum width of
      contrast-enhanced edges. Peritumoral pathological analysis showed distinct
      margins, indicating little or no infiltration of tumor cells into white matter.
      Five cases were classified as cystic and 32 were noncystic GBMs. There was a
      statistically significant difference in age (Mann-Whitney U test; P < 0.05)
      between the patients with cystic tumors (median, 44 years; range, 26-59 years)
      and those with noncystic tumors (median, 54 years; range, 26-81 years). Four of
      the cystic tumors and eight of the noncystic tumors were more than 5 cm in
      maximum diameter. Cystic GBMs had a well-defined tumor interface and less than 2
      cm-thick peritumoral edema compared to the noncystic GBMs (Fisher's exact test; P
      < 0.05). For patients with cystic GBMs, median survival time after surgery was
      19.8 months and the 2-year survival rate was 50%. Patients with noncystic GBMs
      had a median survival time of 12.8 months and a 2-year survival rate of only 17%.
      Median time to tumor recurrence was 13.3 months for patients harboring cystic
      GBMs and 8.5 months for those with noncystic GBMs (log-rank test; P < 0.05).
      Thus, the prognosis for cystic GBM was significantly better than that for
      noncystic GBM, possibly because cystic GBMs showed comparatively little
      infiltration of the peritumoral brain parenchyma.

PMID- 18095117
TI  - Comparison of 1H-MRS-detected metabolic characteristics in single metastatic
      brain tumors of different origin.
AB  - Various types of intracranial metastases exhibit different growth patterns, which
      can be reflected in their metabolic characteristics and investigated
      noninvasively by proton magnetic resonance spectroscopy (1H-MRS). The objective
      of the present study was comparison of the 1H-MRS-detected metabolic parameters
      in brain metastases of different origin. Twenty-five patients (15 men and 10
      women; mean age, 62.0 years) with single, previously nontreated metastatic brain
      tumors were investigated by long-echo single-voxel volume-selected 1H-MRS. The
      primary cancer was located in the lungs (10 cases), colon and rectum (8 cases),
      breast (3 cases), kidney (2 cases), prostate (1 case), and cardiac muscle (1
      case). Comparison of clinical and radiological variables, including type of tumor
      contrast enhancement and extension of peritumoral edema, did not disclose
      statistically significant differences in metastatic brain tumors of different
      origin. At the same time, comparison of 1H-MRS-detected metabolic characteristics
      revealed that metastases of colorectal carcinoma have greater content of mobile
      lipids (Lip) compared to other neoplasms. In conclusion, high Lip content in the
      viable brain metastases of colorectal carcinoma can be used as an additional
      diagnostic clue for noninvasive identification of these tumors and should be
      taken into consideration in cases of 1H-MRS-based differentiation of their
      recurrence and radiation-induced necrosis after radiosurgical or radiotherapeutic
      treatment.

PMID- 18095118
TI  - Detection of genetic and chromosomal aberrations in medulloblastomas and
      primitive neuroectodermal tumors with DNA microarrays.
AB  - Medulloblastoma (MB) is the most frequent infratentorial malignant brain tumor in
      children. In contrast, primitive neuroectodermal tumor (PNET) is defined as a
      supratentorial malignant tumor generated from the cerebral hemisphere. These
      tumors have considerable histological overlap but have different clinical
      outcomes including overall survival period, recurrence rate, and
      chemosensitivity. We investigated the amplification and/or deletion of genes and
      the chromosomal gain and/or loss in 10 MBs and 3 PNETs with a genomic DNA
      microarray system. Genes that are frequently amplified in these both these tumors
      include MSH2, N-myc, AKT3, and EGFR. Amplifications of SNRPN, MYB, and PTEN are
      observed only in MB. The genes associated with Wnt/APC and Shh/PTCH pathways also
      have some aberrations. Common chromosomal aberrations include gains at 17q and 7q
      and losses at 17p. Minor chromosomal losses were also detected at 1p, 8p + q,
      11p, 10p + q, 13q, 16q, and Xp + q in MB. SPNETs tend to contain fewer
      chromosomal and genetic abnormalities than MBs. In conclusion, there are gene
      expression and chromosomal differences between MBs and SPNETs. These differences
      may correlate with the prognosis.

PMID- 18095119
TI  - Scoring radiologic characteristics to predict proliferative potential in
      meningiomas.
AB  - We investigated the feasibility of using radiologic characteristics to predict
      the proliferative potential in meningiomas. Our statistical analysis revealed
      that the presence of peritumoral edema, an ambiguous brain-tumor border, and
      irregular tumor shape were significantly correlated with a higher MIB-1 staining
      index (SI) value. We developed the following scoring system for specific features
      in each tumor: peritumoral edema (tumor with edema = 1, tumor without edema = 0);
      brain-tumor border (tumor with any ambiguous border = 1, tumor circumscribed by a
      distinct rim = 0); and tumor shape (tumor with irregular shape = 1, tumor with
      smooth shape = 0). Using Spearman's correlation coefficient analysis, we found a
      significant correlation (P < 0.005) between total score calculated for each
      patient and SI value. Our findings suggest that the proliferative potential of
      meningiomas can be predicted using a less invasive preoperative examination
      focusing on the presence of peritumoral edema, ambiguous brain-tumor border, and
      irregular tumor shape.

PMID- 18095120
TI  - A case of anaplastic pleomorphic xanthoastrocytoma presenting with tumor bleeding
      and cerebrospinal fluid dissemination.
AB  - Pleomorphic xanthoastrocytoma (PXA) has been considered an astrocytic tumor with
      a relatively favorable prognosis. However, PXA cases having several recurrent
      patterns with poor prognosis have been reported in recent years, and a new
      concept of anaplastic PXA has been proposed. The present case was a 59-year-old
      woman who presented with tumor bleeding onset and cerebrospinal fluid
      dissemination. The patient had sudden-onset right hemiparesis, aphasia, and
      consciousness disturbance and was admitted to a local area hospital. After
      emergency surgery had removed the hematoma, postoperative contrast-enhanced CT
      scan revealed a left temporal tumor. A second surgery was therefore performed for
      initial tumor removal 2 months later. Histopathological findings showed that the
      tumor was typical PXA with strong pleomorphism and xanthomatous changes and
      contained an ependymoma-like component in the center area. However, endothelial
      proliferation and mitosis were more remarkable compared to ordinary PXA. The MIB
      1 labeling index was 9.8% high. From these findings, the histopathological
      diagnosis was anaplastic PXA. The patient underwent surgery to remove recurrent
      tumors 5 and 16 months later. The patient died 36 months after the first onset,
      and CT revealed glioblastoma-like findings and cerebrospinal fluid dissemination.
      This case report is the first case in which PXA presented with tumor bleeding
      onset. Histopathological findings suggested anaplastic PXA from the first
      surgical specimens, and PXA recurred many times. We thus believe that the patient
      displayed primary anaplastic PXA rather than secondary anaplastic PXA that
      results in malignant transformation.

PMID- 18095121
TI  - Giant cell type of primary intracranial malignant fibrous histiocytoma: a case
      report.
AB  - The primary intracranial giant cell type of malignant fibrous histiocytoma (GC
      MFH) is rare, and the resemblance to meningioma causes diagnostic confusion.
      Discrimination from meningioma bears important therapeutic and prognostic
      implications. We report one such case in which an extracranial malignant neoplasm
      was seen after the initial diagnosis and treatment. A 62-year-old woman presented
      with history of seizure. MRI revealed a huge right frontotemporal, homogeneously
      enhanced extraaxial lesion with significant mass effect. The main vascular supply
      was the middle meningeal artery. Workup for lesions elsewhere was negative. Gross
      total resection including dural attachment was achieved. The histopathological
      features were consistent with the diagnosis of GC-MFH. Immunohistochemistry
      disclosed varied reactivity profiles in tumor component cells: the spindle-shaped
      cells possessed features of mesenchymal and hematopoietic lineage, the
      histiocytic cells those of mesenchymal and epithelial cells, and the osteoclast
      like multinucleated giant cells those of monocyte/macrophage and epithelial
      cells. Proliferative activity was absent in giant cells. Local irradiation of 60
      Gy (linac) was performed. The patient did well for 10 months, and follow-up MRI
      showed no evidence of tumor recurrence. Subsequently, she developed ascites and
      died 3 months later as a consequence of end-stage adenocarcinoma (ovary) with
      peritoneal dissemination. There is no established treatment protocol for primary
      intracranial MFH. Although gross total resection and local irradiation were
      effective in the short-term control of local relapse in the present case,
      occurrence of extracranial neoplasm was fatal. Close follow-up aimed at early
      detection of local recurrence and distant metastases, as well as extracranial
      malignancy, remains important.

PMID- 18095122
TI  - Correlation of diagnostic yield of stereotactic brain biopsy with number of
      biopsy bits and site of the lesion.
AB  - Our objective was to examine the reliability of histological diagnosis achieved
      vis a vis the number of biopsy bits obtained along a single trajectory of the
      stereotactic needle. A retrospective analysis of stereotactic biopsies performed
      in a single tertiary care neurosciences center, during a period of 11 years,
      between 1995 to 2005 was done. The overall diagnostic accuracy achieved on
      histopathology was correlated with the number of bits obtained by stereotactic
      biopsy. A total of 86 cases were analyzed, which consisted of 58 males and 28
      females. Age ranged from 6 to 75 years, with a mean age of 36.1 years. Twenty
      percent of the patients were in the pediatric age group and 15% were > or =60
      years of age. Most common sites biopsied were thalamus/basal ganglia (55.8%),
      followed by eloquent areas and other sites. A definitive histological diagnosis
      was established in 70 cases (diagnostic yield, 81.3%), which encompassed 65
      neoplastic and 5 nonneoplastic lesions. Astrocytic lesions, the most common,
      include 10 pilocytic astrocytomas (PA), 29 diffuse astrocytomas (DA), 11
      anaplastic astrocytomas (AA), and 7 glioblastoma multiforme (GBM). In 16 cases no
      definite histological diagnosis could be offered. The number of biopsies ranged
      between 1 and 6 bits (mean, 2; median, 1). The majority (68.7%) of the biopsies
      were 1 or 2-bits. The diagnostic accuracy increased from 76.5% for single
      biopsies to 84% and 88.2% for 2 and 3 bits, respectively, and 100% for biopsies
      with 5 to 6 bits. Overall, a trend of higher diagnostic yield was seen in cases
      with more biopsies when compared with single bit biopsies. Thus, this small
      series confirms that stereotactic procedures involving multiple bits are
      associated with a high diagnostic yield.

PMID- 18095123
TI  - Prognostic implication of p27 expression in primary central nervous system
      lymphoma.
AB  - To clarify the role of p27/Kip1 (p27) in primary central nervous system lymphomas
      (PCNSLs), we examined p27 expression by immunohistochemical methods in a series
      of 22 patients with PCNSL. We attempted to correlate the expression of p27 with
      proliferation potential and prognosis. Although the MIB-1 labeling index (LI) was
      lower in tumors with low p27 expression (26.7% +/- 17.2% vs 38.1% +/- 16.3%), it
      was not significantly different from that of tumors with high p27 expression (P =
      0.1253). Survival analysis revealed that high p27 expression was significantly
      associated with poorer overall prognosis (P = 0.0011); however, the MIB-1 LI were
      not associated with prognosis. Our results suggest p27 as a predictor of
      prognosis in patients with PCNSL.

PMID- 18095125
TI  - A case of tanycytic ependymoma arising from the cerebral hemisphere.
AB  - We report a rare case of tanycytic ependymoma arising from the cerebral
      hemisphere. A 59-year-old man was admitted to our hospital because of the
      incidental detection by MRI of a tumor lesion in the right temporooccipital
      paratrigonal region. The mass showed low-to iso-intensity on T1-weighted images
      and high intensity on T2/proton-weighted images. Partial resection was performed
      using a transsulcal approach to avoid compromising the visual field. Most of the
      tumor cells showed elongated spindle shapes arranged in dense fascicles. A few
      true ependymal rosettes and perivascular pseudorosettes were visible. The tumor
      cells were positive for GFAP, S-100, and vimentin, but negative for
      synaptophysin, EMA, and keratin. The MIB-1 labeling index was approximately 1%.
      Ultrastructurally, the tumor cells had ependymal cell features, such as
      microvilli and cilia. From these findings, a pathological diagnosis of tanycytic
      ependymoma was made.

PMID- 18095124
TI  - Mixed germ cell tumors with abundant sarcomatous component in the temporal lobe
      after radiochemotherapy of neurohypophyseal germinoma: a case report.
AB  - We report a case of intracranial germ cell tumor that showed pathological changes
      from neurohypophyseal germinoma to mixed germ cell tumors consisting exclusively
      of undifferentiated sarcomatous component after radiochemotherapy. Three surgical
      specimens and autopsied brain from the patient were histologically examined. An
      initial specimen from the neurohypophyseal tumor was diagnosed as germinoma with
      a two-cell pattern. Five years later, after repeated radiochemotherapy, the
      second specimen resected from the right temporal lobe showed mixed germ cell
      tumors consisting of the three components of germinoma, choriocarcinoma, and
      immature teratoma. Six months later after intensive radiotherapy, the right
      temporal tumor recurred and was surgically removed. The histological diagnosis
      was mixed germ cell tumors with abundant immature teratoma component. The patient
      died of uncontrollable tumor growth with repeated intratumoral hemorrhages. The
      autopsied brain showed sarcoma with angionecrosis. This pathological alteration
      indicated an increase in the sarcomatous component after undergoing various
      treatments. We discuss the histological changes of intracranial germ cell tumor
      modified by treatment.

PMID- 18095126
TI  - Skull metastasis from papillary thyroid carcinoma accompanied by
      neurofibromatosis type 1 and pheochromocytoma: report of a case.
AB  - We report here a 74-year-old woman with a skull metastasis from papillary thyroid
      carcinoma (PTC). In her medical history, she was diagnosed with neurofibromatosis
      type 1 (NF1) at age 28 years, and she underwent thyroidectomy for PTC at age 52
      years and adrenectomy for pheochromocytoma (PC) at age 58 years. She was admitted
      to our hospital with an increased mass in the forehead. Head computed tomography
      (CT) showed an expansive, osteolytic, and solid tumor extending from the dura
      mater into the subcutis, destroying part of the frontal bone. Head magnetic
      resonance imaging (MRI) revealed that the tumor was chiefly extradural but
      partially invaded the dura mater. Cerebral angiography showed that the tumor was
      fed from a branch of the external carotid artery. She underwent surgery, and
      histological examination revealed that the skull tumor was a metastasis from PTC,
      indicating that skull metastasis occurred 23 years after curative surgery for
      PTC. The patient also underwent adjuvant radioiodine therapy. As little is known
      about skull metastases from PTC, we discuss its characteristics and the extremely
      rare combined occurrence of PC and PTC in an NF1 patient.

PMID- 18095127
TI  - Malignant fibrous histiocytoma in the craniocervical junction presenting with
      severe occipitalgia.
AB  - We report a patient who complained of severe occipitalgia caused by destruction
      of the atlantooccipital joint by tumor invasion. Her symptoms were relieved by
      tumor resection and occipitocervical fixation. Histological examination of the
      resected tumor revealed that the tumor cells had an irregular arrangement,
      remarkable atypia, and pleomorphism with multinucleated bizarre giant cells. The
      tumor demonstrated no definitive sarcoma differentiation and was identified as
      malignant fibrous histiocytoma. After tumor resection, the patient received
      adjuvant radiation and chemotherapy. The tumor regrew outside the radiation
      field. Chemotherapy with ifosfamide, cisplatin, and etoposide caused remarkable
      tumor reduction, but suspension of chemotherapy resulted in tumor recurrence. The
      results of our drug protocol suggest that this regimen is feasible as
      postoperative adjuvant chemotherapy for malignant fibrous histiocytoma. The role
      of adjuvant chemotherapy and radiation therapy for this highly malignant rare
      tumor should be evaluated in a prospective study with precise histological
      diagnosis.

PMID- 18095128
TI  - Two cases of ringlike enhancement on MRI mimicking malignant brain tumors.
AB  - The present study was performed to investigate two cases with ringlike enhanced
      lesions mimicking malignant tumors on magnetic resonance imaging (MRI) and to
      determine the utility of thallium-201 single-photon emission tomography (201Tl
      SPECT) and diffusion-weighted MR imaging (DWI) for differential diagnosis between
      neoplastic and nonneoplastic lesions. One patient was a 50-year-old man who
      presented with a right caudate lesion. The 201Tl-SPECT study revealed no uptake
      in the lesion. Stereotactic biopsy was performed, and pathological findings
      indicated cerebral infarction. The other patient was a 58-year-old woman who
      presented with a right frontal lesion with edema. DWI showed a hypointense
      signal, and the apparent diffusion coefficient (ADC) revealed a hyperintense
      signal in the lesion. Stereotactic biopsy with endoscopy was performed, and the
      pathological findings suggested a demyelinating disease. Combined 201Tl-SPECT and
      DWI studies may be useful for differential diagnosis between neoplastic and
      nonneoplastic lesions. However, stereotactic biopsy should be performed for the
      final pathological diagnosis.

PMID- 18095129
TI  - Hyperprolactinemia and immunohistochemical expression of intracellular prolactin
      and prolactin receptor in primary central nervous system tumors and their
      relationship with cellular replication.
AB  - The role of prolactin (PRL) in the CNS remains uncertain. We evaluated the
      presence of hyperprolactinemia, intracellular prolactin (ICP), and prolactin
      receptor (PRL-R) in primary CNS tumors, and their relationship with cellular
      replication with a prospective cross-sectional study of 82 consecutive patients
      with primary CNS tumors admitted for neurosurgical resection between October 2003
      and September 2005. Patients submitted to a questionnaire, and venous blood
      samples were obtained for measurement of serum PRL and TSH. Immunohistochemical
      analyses were performed to evaluate the presence of ICP, PRL-R, and Ki-67. Serum
      PRL levels ranged from 2 to 70 ng/ml, and hyperprolactinemia was detected in 25
      cases (30.5%). ICP was detected in 18 patients (21.9%), in whom PRL ranged from 2
      to 32 ng/ml. A positive correlation was found between PRL levels and the presence
      of ICP (Student's t test, P = 0.022). The PRL-R was observed
      immunohistochemically in 32 cases (39%). The frequencies of hyperprolactinemia,
      ICP, and PRL-R were similar across the several histological types of CNS tumors.
      Ki-67 index was similar in all groups. Hyperprolactinemia and intracellular
      presence of PRL and PRL-R were common findings in this population, suggesting a
      role for PRL in CNS tumor genesis.

PMID- 18095130
TI  - The usefulness and problem of intraoperative rapid diagnosis in surgical
      neuropathology.
AB  - Intraoperative rapid diagnosis has been a useful neurosurgery tool for maximal
      resection and minimal morbidity. However, only a few studies have been conducted
      regarding diagnostic accuracy and associated problems. The present study reviews
      our experience in treating patients and investigates the accuracy and problems
      associated with intraoperative rapid diagnosis in surgical neuropathology. There
      were 180 cases of intracranial lesions excluding pituitary lesions. The patients
      consisted of 89 males and 91 females, ranging from 5 months to 84 years, with a
      mean age of 46 years. Of the 180 cases, 152 cases received open surgery, 28 cases
      had stereotactic surgery including a biopsy and were histologically verified. The
      correlation between the intraoperative diagnosis and the final diagnosis overall
      was seen in 172 of 180 cases, proving a high diagnostic sensitivity of 95.6%. No
      correlation was seen in 8 cases (4.4%). The diagnostic inaccuracy was seen in the
      grading of gliomas and the diagnosis of undifferentiated malignant tumors such as
      undifferentiated metastatic carcinomas, primitive neuroectodermal tumors (PNETs),
      and sarcomas. It was also recognized in rare types of histology such as
      gliomatosis and xanthomatous lesions. These results suggested that the
      intraoperative rapid diagnosis was quite useful, but that we should also maintain
      a cautious attitude.

PMID- 18095131
TI  - Fluorescence-guided resection of metastatic brain tumors using a 5-aminolevulinic
      acid-induced protoporphyrin IX: pathological study.
AB  - We performed a pathological study to identify the locus of production of
      protoporphyrin IX (PPIX) in human metastatic brain tumors. Patients with
      metastatic brain tumors (n = 11) received 1 g of 5-aminolevulinic acid (5-ALA)
      perorally 2 h before undergoing surgery. The target region was exposed to laser
      light with a peak wavelength of 405 +/- 1 nm and an output of 40 mW. Tissue
      samples from the tumor bulk and surrounding areas were examined by histological
      and fluorescence methods. Of the 11 tumors, 9 manifested PPIX fluorescence in the
      tumor bulk and peritumoral brain tissue. Our findings indicate that PPIX
      fluorescence can be observed in peritumoral edematous areas that are free of
      neoplastic cells, because PPIX produced by neoplastic cells leaks into the
      surrounding edematous area.

PMID- 18095132
TI  - Analysis of immunohistochemical expression of p53 and the proliferation marker Ki
      67 antigen in skull base chordomas: relationships between their expression and
      prognosis.
AB  - The prognosis of chordomas is difficult to predict based solely on histological
      findings. The purpose of this study was to assess the immunohistochemical
      expression of the proliferation marker Ki-67 antigen and the expression of p53 in
      skull base chordomas and to relate their expressions to the outcome. We examined
      the expression of p53 and the MIB-1 labeling index (LI), assessed by Ki-67
      expression, in 19 tumors (initial, n = 11; recurrent, n = 8) from 11 patients.
      The correlation among the MIB-1 LI, p53 expression, and the clinical outcome was
      analyzed. The mean MIB-1 LI and p53 expression at the initial surgery were 5.6 +/
      4.6% and 9.0 +/- 9.4%, respectively. At the time of recurrence, the mean MIB-1
      LI and p53 expression were 10.2 +/- 7.4% and 16.5 +/- 12.0%. The correlation
      between the MIB-1 LI and p53 expression at the initial and recurrent surgeries
      was highly significant (r = 0.948; P < 0.0001). The change in p53 expression from
      the initial to the recurrent chordomas was significantly greater in patients who
      died of tumor-related causes than in the surviving patients. In the surviving
      patients, the values for MIB-1 LI and p53 expression in the recurrent tumors were
      significantly higher in the disease-ongoing group than in the disease-free group.
      Our results suggest that determination of the immunohistochemical expression of
      p53 and Ki-67 antigen is helpful to predict tumor recurrence and prognosis in
      skull base chordomas.

PMID- 18095133
TI  - Malignant transformation of oligoastrocytoma: a case report.
AB  - We report a case of oligoastrocytoma resembling dysembryoplastic neuroepithelial
      tumor (DNT) with malignant transformation. A 35-year-old woman presented with
      headache and generalized convulsion in May 2003. Magnetic resonance imaging (MRI)
      revealed an extensive left temporal lobe tumor. She underwent partial resection
      of the tumor under awake surgery, while preserving her language function. The
      surgical specimen showed that the majority of the tumor was composed of a
      glioneuronal element. However, there was also an abundant oligoastrocytoma
      component. Therefore, our first pathological diagnosis was oligoastrocytoma and
      DNT. She then underwent radiation therapy. The tumor recurred at the left
      temporal lobe in June 2005. She then underwent open biopsy. The pathological
      diagnosis was anaplastic oligoastrocytoma with a MIB-1 staining index of 79%. She
      received PAV (procarvazine, ACNU, and vincristine) chemotherapy, and the tumor
      subsided transiently. However, she died 3 years after the first operation.
      Although the histological findings of the first surgical specimen closely
      resembled those of DNT, radiologic findings and clinical course were different
      from those of DNT. The authors concluded that this tumor could be a malignant
      transformation of oligoastrocytoma mimicking DNT, and we wish to give warning
      that the presence of a glioneuronal component is not an absolute benign hallmark.

PMID- 18095134
TI  - An infant case of intracranial peripheral-type primitive neuroectodermal tumor
      with long-term survival.
AB  - Supratentorial primitive neuroectodermal tumors (S-PNET) that develop in children
      have recently been classified into two types: central-type PNET (C-PNET), which
      has been reported over the years, and peripheral-type PNET (P-PNET), which
      develops intracranially and was referred to as Ewing's sarcoma in the past. P
      PNET is fundamentally a malignant tumor, but the patient reported here represents
      a case of long-term survival from onset without recurrence. At the age of 21
      months, a male infant developed a cranial bone deformity and symptoms of high
      intracranial pressure. A CT scan revealed a cystic tumor attaching to the falx,
      and cyst drainage operation was immediately performed. The intracranial tumor was
      then resected. The tumor was an intradural extramedullary tumor, and it was
      totally excised with the falx attachment. The tumor was initially diagnosed as a
      neuroblastoma, and postoperative treatment consisted of administration of
      radiotherapy and chemotherapy using cyclophosphamide and vincristine. Twenty
      years have now passed without any recurrence. Recent repeated performance of
      histopathological analysis resulted in a diagnosis of P-PNET. In recent years,
      studies in molecular biology have demonstrated that P-PNET involves the EWS-FLI1
      chimeric gene, and immunohistochemical staining has shown P-PNET to be MIC2
      positive. P-PNET also differs from C-PNET with regard to prognosis, and for this
      reason it is believed that P-PNET and C-PNET should be considered separate
      entities. That is, in spite of the fact that P-PNET is a malignant tumor, patient
      survival can be comparatively long. Because P-PNET originates intracranially, it
      is fundamentally an intradural extramedullary tumor. For this reason, treatment
      should consist of surgical excision that is as complete as possible, followed by
      appropriate radiotherapy and chemotherapy. This approach can be expected to
      result in the patient's long-term survival.

PMID- 18095135
TI  - A rare case of malignant glioma suspected to have arisen from a cavernous sinus.
AB  - A 55-year-old woman presented with a right trigeminal dysfunction (dysesthesia)
      initially, followed by right oculomotor and abducens paresis lasting 1 month.
      Neuroimaging studies showed an enhanced mass in the right cavernous sinus
      extending to the trigeminal ganglion. The extraparenchymal tumor located around
      the right trigeminal ganglion was totally removed, except for an intracavernous
      lesion, by the orbitozygomatic approach. The solid tumor was completely separated
      from the brainstem and seemed to be a trigeminal schwannoma arising from the
      trigeminal ganglion or cavernous sinus at surgery. A histological examination,
      however, found a typical malignant glioma that consisted primarily of astrocytic
      tumor cells. Immunohistochemical staining showed the tumor cells stained
      intensely for GFAP, S-100 protein, and vimentin, but not for NFP, Schwann/2E,
      CD34, and CD68. The mean MIB-1 index was 12.4%. The tumor recurred after a short
      time, and then it rapidly disseminated into the subarachnoid space and left the
      cerebral hemisphere. The patient died 1 year after the initial symptoms in spite
      of aggressive surgery, radiation, and chemotherapy with temozolomide. There are
      no previous reports of a malignant glioma arising from either the cavernous sinus
      or the trigeminal ganglion. From the pathogenetic point of view, this malignant
      glioma is an extremely rare case that developed clinically and
      neuroradiologically from the cavernous sinus and was suspected be being derived
      from ectopic glial tissue.

PMID- 18095136
TI  - Expression of aquaporine-4 in central nervous system tumors.
AB  - Cerebral edema is associated with common brain tumors. Aquaporine-4 (AQP4) is a
      member of the water channel protein family, which is thought to be a major factor
      regulating cerebral edema. To elucidate the characterization of the expression of
      AQP4 and the relationship of the expression of VEGF, we investigated the
      expression of AQP4 in tumors of the central nervous system immunohistochemically.
      Brain tumors and nontumorous cerebral tissue for control were evaluated by
      immunohistochemical staining using anti-AQP4, VEGF, CD34, and MIB-1. In tumor
      cells, only glial tumor cells showed a positive reaction for AQP4. The
      reactivities for immunostaining increased according to WHO grades. Reactive glial
      cells in edematous tissue also showed positive reactions. Although endothelial
      cells were negative and/or weakly positive for AQP4, the positive relationship
      suggested the expression of VEGF in endothelial cells in neovasculature and that
      of AQP 4 in tumor cells. APQ4 expression increased in human astrocytic tumors and
      edematous cerebral tissue. Upregulation of APQ4 by tumor cells and reactive
      astroglia were major factors of cerebral edema.

PMID- 18095137
TI  - FISH 1p/19q deletion/imbalance for molecular subclassification of glioblastoma.
AB  - Glioblastoma is the most malignant and frequent of the glial tumors. A minor
      fraction of glioblastoma may contain areas showing oligodendroglioma-like tumor
      cell differentiation. Several authors have described such tumors as glioblastoma
      with oligodendroglial component (GBMO). GBMO may represent the ultimate level of
      malignancy in the oligodendroglial lineage. The oligodendroglial component and
      combined loss of chromosomal arm 1p and 19q in glioblastoma indicate increased
      survival. In our study, we analyzed 1p and 19q status in a series of 12
      glioblastoma and 8 oligodendroglial tumors using fluorescence in situ
      hybridization (FISH) on paraffin-embedded tissues. In each case, hybridization
      status was classified as deletion, imbalance, polysomy, amplification, or normal
      pattern. Other genetic alterations such as CDKN2A (p16), RB, and EGFR were also
      assessed. On histological review, 2 of 12 glioblastoma (16.7%) were classified as
      GBMO. Chromosome 1p/19q deletion was detected in 3 of 12 glioblastomas (25%). In
      contrast, all 8 oligodendroglial tumors showed 1p/19q deletion. All GBMO had 19q
      deletion with imbalance, whereas 1 of 10 ordinary glioblastoma (10%) demonstrated
      19q deletion with imbalance. All but 1 ordinary glioblastoma (90%) showed CDKN2A
      (p16) deletion, but no GBMO displayed this alteration. Our results indicate that
      GBMO may be a distinct subtype of glioblastoma harboring a characteristic
      molecular profile. FISH on paraffin-embedded specimens is a useful method for
      subclassification of glioblastoma.

PMID- 18095138
TI  - Early effects of boron neutron capture therapy on rat glioma models.
AB  - Early effects of boron neutron capture therapy (BNCT) on malignant glioma are
      characterized by reduction of the enhancement area and regression of the
      peritumoral edema radiologically. The aim of this study was to investigate the
      early histological changes of tumors and inflammatory cells after BNCT in the rat
      brain. Rats were treated with BNCT using boronophenylalanine (BPA) 7 days after
      implantation of C6 glioma cells. The tumors were assessed with magnetic resonance
      imaging and histopathological examination at 4 days after BNCT. The mean tumor
      volumes were 39 +/- 2 mm3 in the BNCT group and 134 +/- 18 mm3 in the control
      group. In the BNCT group, tumor cells showed a less pleomorphic appearance with
      atypical nuclei and mitotic figures. The Ki-67 labeling index was 6.5% +/- 4.7%
      in the BNCT and 35% +/- 3.8% in the control group. The reactions of the
      inflammatory cells were examined with ED-1 as macrophage marker and OX42 as
      microglia marker. ED-1- and OX-42-positive cells were reduced both in the core
      and the marginal area of the tumor in the BNCT group. It is suggested that BNCT
      reduced tumor progression by suppression of proliferation. Inhibition of the
      activated macrophages may relate to reduced peritumoral edema in the early phase.

PMID- 18095139
TI  - Comparison of numerical change of epidermal growth factor receptor gene among pre
      and postradiation glioma, and gliosis, and its clinical use.
AB  - Surgery with following chemoradiotherapy is the mainstream glioma treatment. In
      the course of postradiation events, however, it is sometimes difficult for
      neurosurgeons, radiologists, and pathologists to discriminate tumor recurrence
      from radiation necrosis. The epidermal growth factor receptor (EGFR) gene, on
      chromosome 7, is known to gain in copy number frequently in high-grade gliomas.
      The authors applied the fluorescence in situ hybridization (FISH) method to
      observe the gene's numerical status in pre- and postradiation glioma samples to
      elucidate whether this technique is useful in the discrimination of glioma
      recurrence from radiation necrosis. When 15 postradiation glioma samples and 4
      postradiation nonglioma samples were tested, all the recurrent glioma tissue
      harbored numerical aberrations of the gene, whereas no abnormality could be
      observed in necrosis or in nonglioma gliosis. FISH could even prove a residual
      glioma cell in a gliotic tissue taken by needle biopsy after gamma-knife
      radiosurgery, which had been executed on a supposed metastatic brain tumor. FISH
      is considered to be of help in accurate diagnosis, especially when the usual
      histopathological diagnosis is difficult because of radiation effects or small
      sample size.

PMID- 18095140
TI  - A rare case of extraventricular neurocytoma.
AB  - We report an unusual case of extraventricular (cerebral) neurocytoma with a long,
      25-year history, and which appeared to transform to neuroblastoma. In 1978, an 18
      year-old woman was treated for right frontal oligodendroglioma. Eighteen years
      later (in 1996), recurrence of tumor in the fourth ventricle was noted and was
      treated with gamma-knife radiotherapy. The tumor shrunk transiently, but 7 years
      later (in 2004), MRI study demonstrated a second recurrence and ventricular
      dissemination. Partial removal was performed, and histological examination
      revealed that tumor cells had round or oval nuclei with halos. Frequent mitoses
      and vascular proliferation were observed. The MIB-1 LI was 80%. Despite
      postoperative whole-brain radiotherapy to a total dose of 30 Gy, the tumor
      progressed, and she died at 4 months after the second surgery.

PMID- 18095141
TI  - Ectopic recurrence of dysplastic gangliocytoma of the cerebellum (Lhermitte
      Duclos disease): a case report.
AB  - Lhermitte-Duclos disease is a rare clinical entity characterized by slow
      deformation of the cerebellar lesion. A 53-year-old woman presented with
      Lherimitte-Duclos disease manifesting as ataxic gait, occipital headache, and
      loss of consciousness. Magnetic resonance imaging demonstrated striated and
      laminar pattern lesions in the right cerebellar hemisphere and vermis. She
      underwent subtotal removal of the vermis compressing the brainstem, but the
      cerebellar hemisphere appeared normal and was preserved. Histological findings
      were consistent with Lherimitte-Duclos disease. Two years later, magnetic
      resonance imaging revealed enlargement of the right hemispheric lesion.
      Intraoperative appearance of the hemisphere demonstrated marked enlargement of
      the folia. Subtotal removal was performed. Histological examination showed no
      malignant findings. Lhermitte-Duclos disease may recur, and should be carefully
      followed up as a low-grade neoplasm, not as a hamartomatous disorder.

PMID- 18095142
TI  - Recurrent intracranial solitary fibrous tumor initially diagnosed as
      hemangiopericytoma.
AB  - We describe a case of an intracranial solitary fibrous tumor that recurred three
      times consecutively in an 11-year period. A 72-year-old man presented with a
      headache and gait disturbance. Magnetic resonance imaging (MRI) revealed a
      dumbbell tumor at the left tentorium. The tumor was removed but recurred. The
      first diagnosis was hemangiopericytoma, but all specimens showed a "patternless
      pattern" and few reticulin fibers, which features were not compatible with
      hemangiopericytoma. All tumors showed immunoreactivity for CD34 and bcl-2. These
      results point to a solitary fibrous tumor (SFT) and not to hemangiopericytoma. We
      present here a hypercellular spindle-cell tumor that was very similar to
      hemangiopericytoma but is better diagnosed as SFT.

PMID- 18095143
TI  - Supratentorial ectopic cortical ependymoma occurring with intratumoral
      hemorrhage.
AB  - We report here a rare case of supratentorial ectopic cortical ependymoma. This
      tumor was localized in the left angular gyrus, occurred with intratumoral
      hemorrhage, was attached to the dura mater, exhibited no continuity with the
      ventricular system, showed distinctive pathological features (perivascular pseudo
      rosette formations and firework-like giant rosette formations), and finally
      transformed to a glioblastoma-like high-grade lesion. A cortical ependymoma
      should be considered in the differential diagnosis of supratentorial cortical
      tumors with intraparenchymal hemorrhage and high vascularity, even if not in
      contact with the ventricular system. Although malignant transformation is unusual
      in cortical ependymoma, close observation and adjunctive radiotherapy are
      strongly recommended after the excision.

PMID- 18095144
TI  - Oxidative stress and the genomic regulation of aldosterone-stimulated NHE1
      activity in SHR renal proximal tubular cells.
AB  - This study evaluated the effects of aldosterone upon Na+/H+ exchange (NHE)
      activity in immortalized proximal tubular epithelial (PTE) cells from the
      spontaneously hypertensive rat (SHR) and the normotensive controls (Wistar Kyoto
      rat; WKY). Increases in NHE activity after exposure to aldosterone occurred in
      time- and concentration-dependent manner in SHR PTE cells, but not in WKY PTE
      cells. The aldosterone-induced increases in NHE activity were prevented by
      spironolactone, but not by the glucocorticoid receptor antagonist Ru 38486. The
      presence of the mineralocorticoid receptor transcript was confirmed by PCR and
      NHE1, NHE2, and NHE3 proteins were detected by immunoblot analysis. Cariporide
      and EIPA, but not S3226, inhibited the aldosterone-induced increase in NHE
      activity, indicating that NHE1 is the most likely involved NHE isoform.
      Pretreatment of SHR PTE cells with actinomycin D attenuated the aldosterone
      induced increases in NHE activity. The SHR PTE cells had an increased rate of
      H2O2 production when compared with WKY PTE cells. Treatment of cells with
      apocynin, a NADPH oxidase inhibitor, markedly reduced the rate of H2O2
      production. The aldosterone-induced increase in NHE activity SHR PTE cells was
      completely prevented by apocynin. In conclusion, the aldosterone-induced
      stimulation of NHE1 activity is a genomic event unique in SHR PTE cells, which
      involves the activation of the mineralocorticoid receptor, but ultimately
      requires the availability of H2O2 in excess.

PMID- 18095145
TI  - Quantitative solubility relationships and the effect of water uptake in
      triglyceride/monoglyceride microemulsions.
AB  - PURPOSE: This paper aims to elucidate quantitative relationships between small
      molecule solubility/water-uptake in triglyceride/monoglyceride lipid
      formulations, the chemical structure of the solute, and the solvent composition.
      METHODS: Solubility and water uptake in tricaprylin/1-monocaprylin and
      tricaprylin/1-monocaprin mixtures in the "microemulsion" region at 37 degrees C
      were determined with HPLC and KF coulometry, respectively. Twelve model solutes
      varying in hydrogen bond acidity, basicity, polarity, and molecular volume were
      chosen. Linear free energy relationships (LFER) (Abraham type) were implemented
      to obtain solvent coefficients at various monoglyceride concentrations. RESULTS:
      Profiles for both solubility and water uptake (at different water activities) in
      lipid mixtures containing different monoglycerides were superimposable, producing
      a single master curve when the monoglyceride concentrations were plotted on a
      molar scale. The LFER derived solvent coefficients showed a systematic dependence
      on the lipid composition consistent with the view that relative solubility is
      determined largely by the molar concentrations of individual functional groups
      such as glyceride ester moieties and hydroxyl groups. At low RH, water uptake
      increased linearly with monoglyceride concentration while cooperativity was
      evident in water uptake profiles at high RH. CONCLUSIONS: This study provides a
      potential universal framework for predicting relative drug solubility in mixtures
      containing fully saturated triglycerides and monoglycerides.

PMID- 18095146
TI  - Life skills, mathematical reasoning and critical thinking: a curriculum for the
      prevention of problem gambling.
AB  - Previous studies have shown that youth are two to three times more likely than
      adults to report gambling related problems. This paper reports on the development
      and pilot evaluation of a school-based problem gambling prevention curriculum.
      The prevention program focused on problem gambling awareness and self-monitoring
      skills, coping skills, and knowledge of the nature of random events. The results
      of a controlled experiment evaluating the students learning from the program are
      reported. We found significant improvement in the students' knowledge of random
      events, knowledge of problem gambling awareness and self-monitoring, and
      knowledge of coping skills. The results suggest that knowledge based material on
      random events, problem gambling awareness and self-monitoring skills, and coping
      skills can be taught. Future development of the curriculum will focus on content
      to expand the students' coping skill options.

PMID- 18095147
TI  - On the diagnosticity of multiple-witness identifications.
AB  - It is not uncommon for there to be multiple eyewitnesses to a crime, each of whom
      is later shown a lineup. How is the probative value, or diagnosticity, of such
      multiple-witness identifications to be evaluated? Previous treatments have
      focused on the diagnosticity of a single eyewitness's response to a lineup (Wells
      and Lindsay, Psychol. Bull. 3 (1980) 776); however, the results of eyewitness
      identification experiments indicate that the responses of multiple independent
      witnesses may often be inconsistent. The present paper calculates response
      diagnosticity for multiple witnesses and shows how diagnostic probabilities
      change across various combinations of consistent and inconsistent witness
      responses. Multiple-witness diagnosticity is examined across variation in the
      conditions of observation, lineup composition, and lineup presentation. In
      general, the diagnostic probabilities of guilt were shown to increase with the
      addition of suspect identifications and decrease with the addition of
      nonidentifications. Foil identification results were more complicated-diagnostic
      of innocence in many cases, but nondiagnostic or diagnostic of innocence in
      biased lineups. These analyses illustrate the importance of securing clear
      records of all witness responses, rather than myopically focusing on the witness
      who identified the suspect while ignoring those witnesses who did not.

PMID- 18095148
TI  - Correction of anemia with erythropoietin in chronic kidney disease (stage 3 or
      4): effects on cardiac performance.
AB  - BACKGROUND: It is not clear whether the correction of anemia with erythropoietin
      (rhuEpo) in patients with chronic kidney disease (CKD) has any benefit on cardiac
      function and geometry. Most studies are based on indices of systolic function and
      left ventricular mass (LVM) and the results are conflicting. PATIENTS AND
      METHODS: We sought to investigate the effect of rhuEpo on LV systolic and
      diastolic performance using conventional and novel echocardiographic indices.
      Thirty one patients with CKD (stage 3 or 4) were included. Fifteen patients
      (group I) treated with rhuEpo targeting at Hb >or=13.0 g/dL, while the remaining
      (group II) were not treated. Clinical and laboratory parameters were recorded at
      baseline and 1 year later. Ejection fraction (EF) and LVM were carefully
      determined. Diastolic function was assessed by mitral inflow indices (E and A
      wave velocities, Edt deceleration time and E/A) and novel indices of mitral
      annulus motion using Tissue Doppler Imaging (Em, Am, and E/Em). An index of
      global cardiac function (Tei) was also calculated. RESULTS: At baseline, the 2
      groups had comparable clinical and laboratory characteristics. After 1 year, a
      significant improvement in Hb levels (13.6 +/- 1.2 vs 10.3 +/- 1.2 g/dL, p <
      0.05) as well as in systolic and diastolic function indexes was observed in group
      I compared to group II patients: EF (70.5 +/- 7.6 vs 63.4 +/- 9.3%, p < 0.05),
      LVM (116.5 +/- 34.9 vs 155.6 +/- 51.6 g/m(2), p < 0.05), Edt (233.9 +/- 98.6 vs
      166.9 +/- 45.1 ms, p < 0.05), Tei index (0.35 +/- 0.12 vs 0.51 +/- 0.17, p <
      0.01) and E/Em (9.7 +/- 2.4 vs 14.8 +/- 5.2, p < 0.05), respectively. Blood
      pressure and heart rate did not show significant changes. CONCLUSIONS: Correction
      of anemia with rhuEpo in patients with CKD seems to improve cardiac performance
      and geometry.

PMID- 18095149
TI  - Development of the evaluative method for evaluating and determining evidence
      based practices in autism.
AB  - Although research in autism has grown more sophisticated, the gap between
      research knowledge and applicability of research in real world settings has
      grown. There have been a number of different reviews of evidence-based practices
      of treatments for young children with autism. Reviews which have critically
      evaluated the empirical evidence have not found any treatments that can be
      considered evidence-based. Reasons for this shortcoming are explored, and a new
      method for the evaluation of empirical evidence is provided. Future uses of this
      evaluative method are provided as well as a discussion of how this tool might aid
      in narrowing the research to practice gap.

PMID- 18095152
TI  - Breast cancer risk and the BRCA1 interacting protein CTIP.
AB  - Mutations in BRCA1 predispose to breast cancer. CTIP interacts with BRCA1 and so
      could also be associated with increased risk. We screened CTIP for germline
      mutations in 210 probands of breast cancer families including 129 families with
      no mutations in BRCA1 or BRCA2. No coding variants were detected in CTIP,
      therefore, it is unlikely to be involved in breast cancer risk.

PMID- 18095150
TI  - Posttraumatic stress disorder, alcohol use, and physical health concerns.
AB  - PTSD is a risk factor for alcohol problems and both in turn have been
      independently associated with increased health problems. However, it is unclear
      whether alcohol use moderates the relationship between PTSD and health.
      Participants were battered women (N = 336) recruited from local domestic violence
      shelters and non-shelter victim-assistance agencies. A 2 (PTSD diagnosis) x 3
      (abstainer, infrequent/light, regular/heavy drinking) ANCOVA was conducted, with
      injuries and length of abuse as covariates and health concerns as the dependent
      variable. Main effects for PTSD and alcohol use were significant but not the
      interaction. Women with PTSD reported the greatest number of health concerns.
      Women who abstained from drinking and those who drank regularly/heavily reported
      more health concerns than the infrequent/light drinkers. Health concerns
      associated with PTSD do not appear to be due to problem drinking. In addition,
      infrequent/light drinking, even for women with PTSD, may be associated with fewer
      health concerns.

PMID- 18095153
TI  - Targeted disruption of Brca1 in restricted compartments of the mouse mammary
      epithelia.
AB  - Tumours arising in BRCA1 mutation carriers have a characteristic phenotype, the
      molecular and cellular basis of which is unknown. To address the hypothesis that
      this phenotype reflects a role for BRCA1 in either in the basal or the stem cell
      compartments of the mammary epithelia, we have targeted its disruption to K14 and
      K6a expressing cells of the mouse. Unlike MMTV and WAP driven conditional
      knockout models of Brca1, these two models did not result in any observable
      changes in the mammary gland. Our results suggest that BRCA1-associated tumours
      arise either in K14 and K6a negative basal cells of the mammary gland, or
      possibly from transdifferentiation of luminal epithelia.

PMID- 18095154
TI  - Use of expression data and the CGEMS genome-wide breast cancer association study
      to identify genes that may modify risk in BRCA1/2 mutation carriers.
AB  - Germline mutations in BRCA1 or BRCA2 confer an increased lifetime risk of
      developing breast or ovarian cancer, but variable penetrance suggests that cancer
      susceptibility is influenced in part by modifier genes. Microarray expression
      profiling was conducted for 69 irradiated lymphoblastoid cell lines derived from
      healthy controls, or from cancer-affected women with a strong family history of
      breast and ovarian cancer carrying pathogenic mutations in BRCA1 or BRCA2, or
      with no BRCA1/2 mutations (BRCAX). Genes discriminating between BRCA1, BRCA2 or
      BRCAX and controls were stratified based on irradiation response and/or cell
      cycle involvement. Gene lists were aligned against genes tagged with single
      nucleotide polymorphisms (SNPs) determined by the Cancer Genetic Markers of
      Susceptibility (CGEMS) Breast Cancer Whole Genome Association Scan to be
      nominally associated with breast cancer risk. Irradiation responsive genes whose
      expression correlated with BRCA1 and/or BRCA2 mutation status were more likely to
      be tagged by risk-associated SNPs in the CGEMS dataset (BRCA1, P = 0.0005; BRCA2,
      P = 0.01). In contrast, irradiation responsive genes correlating with BRCAX
      status were not enriched in the CGEMS dataset. Classification of expression data
      by involvement in cell cycle processes did not enrich for genes tagged by risk
      associated SNPs, for BRCA1, BRCA2 or BRCAX groups. Using a novel combinatorial
      approach, we have identified a subset of irradiation responsive genes as high
      priority candidate BRCA1/2 modifier genes. Similar approaches may be used to
      identify genes and underlying genetic risk factors that interact with exogenous
      stimulants to cause or modify any disease, without a priori knowledge of the
      pathways involved.

PMID- 18095155
TI  - Chronic nicotine alters nicotinic receptor-induced presynaptic Ca2+ responses in
      isolated nerve terminals.
AB  - Brain nicotinic receptors display pronounced permeability for Ca2+ and localize
      to presynaptic nerve terminals, in addition to postsynaptic sites. Chronic
      exposure to nicotine has been shown to alter brain nicotinic receptor expression,
      but the functional consequences for presynaptic Ca2+ have not been directly
      examined. Here, we used confocal imaging to assess Ca2+ responses in individual
      nerve terminals from cortices of mice treated up to 14 days with nicotine as
      compared to vehicle-treated controls. Chronic nicotine treatment led to
      substantially enhanced amplitudes of presynaptic Ca2+ responses to acute
      application of nicotine at concentrations of 50 nM (2-fold) and 500 nM (1.7
      fold), but not 50 microM. In addition, increased expression of high-affinity
      nicotinic receptors on isolated terminals was observed following chronic
      treatment, as determined immunocytochemically and pharmacologically. These
      findings suggest that chronic exposure to nicotine may lead to enhanced
      sensitivity to nicotine at select presynaptic sites in brain via up-regulation of
      high-affinity nicotinic receptors.

PMID- 18095156
TI  - Spatiotemporal expression of PSD-95 and nNOS after rat sciatic nerve injury.
AB  - Neuronal nitric oxide synthase (nNOS) has been implicated to influence peripheral
      nerve lesion and regeneration. Post-synaptic density-95 (PSD-95) is one of nNOS
      anchoring proteins and plays an important role in specifying the sites of
      reaction of NO in nervous system. Here we established a rat sciatic nerve crush
      (SNC) model to examine the spatiotemporal expression of PSD-95 and nNOS. At gene
      levels, PSD-95 mRNA diminished shortly after crush, and significantly elevated
      from 2 days to 2 weeks, whereas nNOS decreased progressively post-operation,
      reached the valley at 1 day, and markedly up-regulated from 1 to 2 weeks after
      SNC. The expression of both molecules returned to the control level at 4 weeks
      post-injury. At protein levels, PSD-95 and nNOS underwent the similar changes as
      their gene expression except for a time lag during up-regulating. At their peak
      expression, PSD-95 co-labeled with nNOS in Schwann cells (SCs) of sciatic nerve
      within 0.5 mm from the lesion site, but had few colocalization in axons. In
      addition, the interaction between PSD-95 and nNOS enhanced significantly at 2
      weeks after SNC. These results suggest a correlation of PSD-95 up-regulation with
      nNOS in reactive SCs of crushed sciatic nerve, which may lead to understanding
      the function of PSD-95 during peripheral nerve regeneration.

PMID- 18095157
TI  - Decreased fractalkine and increased IP-10 expression in aged brain of APP(swe)
      transgenic mice.
AB  - Chemokines and their receptors have been strongly implicated in the inflammatory
      process and pathogenesis of the neurodegenerative disorders, such as Alzheimer's
      disease (AD). In the present study, we examined the expression of chemokines,
      fractalkine, interferon-inducible protein-10 (IP-10) and macrophage inflammatory
      protein-1alpha (MIP-1alpha) by immunohistochemistry in the brain of transgenic
      mice APP SWE (Tg2576) at ages of 9, 11, and 17 months, which over-express a
      mutated form of human amyloid precursor protein (APP). Decreased fractalkine and
      increased IP-10 expression in cerebral cortex and hippocampus were found at ages
      of 9 and 17 months in Tg2576 mice when compared with age-matched control mice. On
      the contrary, MIP-1alpha expression showed no difference between Tg2576 mice and
      aged controls and was not influenced by ages. beta-amyloid (Abeta) positive
      plaques were co-located with the intense IP-10 expression. The finding suggests
      fractalkine and IP-10 may participate in the pathogenesis of AD; and could be new
      therapeutic strategies for neuroprotection.

PMID- 18095158
TI  - Changes in Glial cell line-derived neurotrophic factor expression in the rostral
      and caudal stumps of the transected adult rat spinal cord.
AB  - Limited information is available regarding the role of endogenous Glial cell line
      derived neurotrophic factor (GDNF) in the spinal cord following transection
      injury. The present study investigated the possible role of GDNF in injured
      spinal cords following transection injury (T(9)-T(10)) in adult rats. The
      locomotor function recovery of animals by the BBB (Basso, Beattie, Bresnahan)
      scale score showed that hindlimb support and stepping function increased
      gradually from 7 days post operation (dpo) to 21 dpo. However, the locomotion
      function in the hindlimbs decreased effectively in GDNF-antibody treated rats.
      GDNF immunoreactivty in neurons in the ventral horn of the rostral stump was
      stained strongly at 3 and 7 dpo, and in the caudal stump at 14 dpo, while
      immunostaining in astrocytes was also seen at all time-points after transection
      injury. Western blot showed that the level of GDNF protein underwent a rapid
      decrease at 7 dpo in both stumps, and was followed by a partial recovery at a
      later time-point, when compared with the sham-operated group. GDNF mRNA-positive
      signals were detected in neurons of the ventral horn, especially in lamina IX. No
      regenerative fibers from corticospinal tract can be seen in the caudal segment
      near the injury site using BDA tracing technique. No somatosensory evoked
      potentials (SEP) could be recorded throughout the experimental period as well.
      These findings suggested that intrinsic GDNF in the spinal cord could play an
      essential role in neuroplasticity. The mechanism may be that GDNF is involved in
      the regulation of local circuitry in transected spinal cords of adult rats.

PMID- 18095159
TI  - Orocecal transit time in patients in the chronic phase of corrosive injury.
AB  - Accidental/suicidal ingestion of corrosive substances is common in North India.
      Decreased gastric secretion and delayed gastric emptying in the chronic phase of
      corrosive injury has been documented at our center. We hypothesize that patients
      in the chronic phase of corrosive injury may have delayed orocecal transit time
      (OCTT). OBJECTIVE: To measure the orocecal transit time (using the noninvasive
      method of lactulose hydrogen breath test) in patients in the chronic phase of
      corrosive injury. METHODS: Thirty patients with corrosive injury to their
      gastrointestinal tract with its sequelae and attending the gastroenterology
      services of PGIMER, Chandigarh for endoscopic dilatation of strictures were
      enrolled in this study. Patients with age >60 years, vagotomy, prior gastric
      surgery, peptic ulcer disease, systemic sclerosis, history of diabetes,
      hypothyroidism or intestinal pseudo-obstruction were excluded. Orocecal transit
      time was measured by using a 15 mL lactulose hydrogen breath test. End expiratory
      breath was taken every 10 min until there was a rise >10 ppm over the fasting
      value in two consecutive readings. RESULTS: Thirty patients (11 females and 19
      males) with a median age of 32 years, 27 with acid ingestion and 3 with alkali
      ingestion, were studied. None had symptoms of gastric outlet obstruction or
      gastroparesis. OCTT was significantly prolonged in the study group as compared to
      the control group (135.4 +/- 15.8 versus 90.6 +/- 10.4 min). No significant
      difference was observed between different age groups, gender, and type of caustic
      agent consumed. OCTT was maximally prolonged in patients with involvement of
      lower oesophagus, whereas patients without lower oesophagus involvement did not
      show significantly altered OCTT. CONCLUSION: Our results show that patients with
      corrosive injury have prolonged OCTT even in the absence of any gastric symptoms.
      OCTT was prolonged maximally in patients with lower-third oesophageal
      cicatrization. This may a result of autovagotomy due to vagal entrapment in the
      cicatrization process involving the lower third of oesophagus.

PMID- 18095160
TI  - Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity
      in the sera of patients with pancreatic cancer.
AB  - BACKGROUND: Numerous experiments have shown that alcohol dehydrogenase (ADH) and
      aldehyde dehydrogenase (ALDH) are present in cells of various cancer and can play
      role in carcinogenesis. In previous investigations we have found elevated levels
      of alcohol dehydrogenase class III activity in pancreatic cancer cells. It can
      suggest that these changes may be reflected by enzyme activity in the serum. AIM:
      In this paper we have measured the activity of alcohol dehydrogenase isoenzymes,
      and aldehyde dehydrogenase in the sera of patients with pancreatic cancer.
      METHODS: Serum samples were taken for routine biochemical investigation from 56
      patients with pancreatic cancer before treatment. Total ADH activity was measured
      by photometric method with p-nitrosodimethylaniline (NDMA) as a substrate, and
      ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde as a
      substrate. For the measurement of the activity of class I isoenzymes, we employed
      the fluorometric methods, with class-specific fluorogenic substrates. The
      activity of class III alcohol dehydrogenase was measured by the photometric
      method with n-octanol and class IV with m-nitrobenzaldehyde as a substrate.
      RESULTS: A statistically significant increase of class III alcohol dehydrogenase
      isoenzymes was found in the sera of cancer patients. The median activity of this
      class isoenzyme in the total cancer group increased about 22% (13.52 mU/l) in the
      comparison with the control level (11.08 mU/l). The total alcohol dehydrogenase
      activity was significantly higher (19.7%) among patients with cancer than healthy
      ones. The activities of other tested ADH isoenzymes and total ALDH were
      unchanged. The activity of the class I ADH isoenzyme was significantly higher in
      the sera of drinkers with pancreatic cancer than non-drinkers. CONCLUSION: The
      increased total activity of alcohol dehydrogenase and class III isoenzyme in the
      sera of patients with pancreatic cancer can be caused by release of this
      isoenzyme from cancer cells.

PMID- 18095162
TI  - Extra digestive manifestations of irritable bowel syndrome: intolerance to drugs?
AB  - Patients with IBS frequently complain of medication side effects. The goals of
      this study were to assess the prevalence of drug intolerance as an extra GI
      manifestation in patients with IBS and to verify the association between drug
      intolerance and psychological comorbidity. Female patients followed in a tertiary
      care center completed questionnaires assessing the presence of drug intolerance
      as well as somatic and psychological extra GI conditions. IBS patients (Rome II
      criteria; n = 71) were compared to inflammatory bowel disease patients (IBD; n =
      96) or to healthy controls (HC; n = 67). The relationship to psychological
      comorbidity was verified in two different paradigms: (1) by looking at the
      statistical correlation between drug intolerance and the psychological extra GI
      symptoms in our IBS patients, and (2) by comparing in a meta-analysis the side
      effects to placebo (the nocebo effect is presumably increased due to
      hypervigilance or amplification in psychological disorders) in IBS patients or in
      patients with comparable medical conditions included in various drug trials
      approved by Health Canada. Our results show that prevalence of drug intolerance
      was significantly more elevated in IBS (41% patients) than in HC (7%) or in IBD
      (27%); somatic and psychological extra GI symptoms were also markedly increased
      in IBS. In addition, drug intolerance in our IBS patients was significantly
      associated with somatic comorbidities such as fatigue or multiple symptoms (P <
      0.001), but not with psychological factors such as depression, anxiety, mood
      instability, or sleep disorder. A meta-analysis revealed that the nocebo effect
      was not different in patients with IBS than in control patients. In conclusion,
      drug intolerance is a frequent extra GI manifestation of IBS that is not
      associated with psychological comorbidity; thus, a somatic origin must be
      explored.

PMID- 18095161
TI  - Glucocorticoid availability in colonic inflammation of rat.
AB  - Recent in vitro studies have shown the involvement of pro-inflammatory cytokines
      in the regulation of the local metabolism of glucocorticoids via 11beta
      hydroxysteroid dehydrogenase type 1 and type 2 (11HSD1 and 11HSD2). However,
      direct in vivo evidence for a relationship among the local metabolism of
      glucocorticoids, inflammation and steroid enzymes is still lacking. We have
      therefore examined the changes in the local metabolism of glucocorticoids during
      colonic inflammation induced by TNBS and the consequences of corticosterone
      metabolism inhibition by carbenoxolone on 11HSD1, 11HSD2, cyclooxygenase 2 (COX
      2), mucin 2 (MUC-2), tumor necrosis factor alpha (TNF-alpha), and interleukin
      1beta (IL-1beta). The metabolism of glucocorticoids was measured in tissue slices
      in vitro and their 11HSD1, 11HSD2, COX-2, MUC-2, TNF-alpha, and IL-1beta mRNA
      abundances by quantitative reverse transcription-polymerase chain reaction.
      Colitis produced an up-regulation of colonic 11HSD1 and down-regulation of 11HSD2
      in a dose-dependent manner, and these changes resulted in a decreased capacity of
      the inflamed tissue to inactivate tissue corticosterone. Similarly, 11HSD1
      transcript was increased in colonic intraepithelial lymphocytes of TNBS-treated
      rats. Topical intracolonic application of carbenoxolone stimulated 11HSD1 mRNA
      and partially inhibited 11HSD2 mRNA and tissue corticosterone inactivation and
      these changes were blocked by RU-486. The administration of budesonide mimicked
      the effect of carbenoxolone. In contrast to the local metabolism of
      glucocorticoids, carbenoxolone neither potentiates nor diminishes gene expression
      for COX-2, TNF-alpha, and IL-1beta, despite the fact that budesonide down
      regulated all of them. These data indicate that inflammation is associated with
      the down-regulation of tissue glucocorticoid catabolism. However, these changes
      in the local metabolism of glucocorticoids do not modulate the expression of COX
      2, TNF-alpha, and IL-1beta in inflamed tissue.

PMID- 18095163
TI  - Synergistic regulation of COX-2 expression by bombesin and transforming growth
      factor-beta.
AB  - Overexpression of cyclooxygenase-2 (COX-2), an inducible enzyme regulating
      prostaglandin release, is mechanistically linked to the development, growth, and
      spread of gastrointestinal (GI) cancers. GI peptide bombesin (BBS) was reported
      to stimulate COX-2 gene expression. Here we show that TGF-beta1 dramatically
      enhances the BBS-induced expression of COX-2 mRNA and protein, and the release of
      PGE2 in the model rat intestinal epithelial cell (RIE-1) line. The synergistic
      increase in COX-2 levels results from a combination of enhanced COX-2
      transcription and reduced mRNA degradation. BBS, but not TGF-beta1, stimulated
      COX-2 promoter activity, and TGF-beta1 enhanced COX-2 mRNA stability through a
      p38(MAPK)-dependent pathway. The synergistic regulation of COX-2 expression by
      TGF-beta1 and BBS may contribute to the upregulation of COX-2 in GI cancers.

PMID- 18095164
TI  - Prognostic impact of perineural invasion following pancreatoduodenectomy with
      lymphadenectomy for ampullary carcinoma.
AB  - The aim of this study was to identify prognostic factors in patients undergoing
      pancreatoduodenectomy with lymphadenectomy for ampullary carcinoma. The records
      of 46 consecutive patients with ampullary carcinoma who underwent
      pancreatoduodenectomy from 1988 through 2006 were retrospectively reviewed. A 98%
      rate of potentially curative (R0) resection was achieved. There was no 30-day
      mortality. Overall 5-year survival rate was 64%. Univariate analysis revealed
      that T3 and T4 tumor (i.e., pancreatic parenchymal invasion) (P < 0.001), lymph
      node metastasis (P = 0.01), and perineural invasion (P < 0.001) were significant
      predictors of poor prognosis. Furthermore, perineural invasion was found to be a
      significant independent predictor of poor prognosis by multivariate analysis (P =
      0.024). Pancreatoduodenectomy with lymphadenectomy for ampullary carcinoma is a
      safe surgical procedure with an acceptable cure rate. The presence of perineural
      invasion may be useful for predicting poor prognosis in patients with ampullary
      carcinoma who undergo potentially curative resection.

PMID- 18095165
TI  - Pathophysiological characteristics of dimethylnitrosamine-induced liver fibrosis
      in acute and chronic injury models: a possible contribution of KLF5 to fibrogenic
      responses.
AB  - Dimethylnitrosamine administration induces a rapid increase in collagen
      deposition with concomitant proliferation of hepatic stellate cells in rats.
      Here, we investigated the pathophysiological profiles of acute and chronic
      hepatic fibrosis states and attempted to determine the possible role of Kruppel
      like factor-5 (KLF5) in this model. In acute study using a single drug injection,
      we observed a rapid transient increase of ALT and mRNA levels of KLF5 followed by
      increases in fibrosis-related genes. Repeated administration of
      dimethylnitrosamine once a week caused early damage with severe fibrosis and
      sustained hepatocyte injury, while intermittent injections at 2-week intervals
      induced only modest fibrosis from 3 weeks. Weekly administration also induced
      profound upregulation of collagen I, alpha-smooth muscle actin, and KLF5 mRNA. In
      contrast, such continued augmentation was not observed after intermittent
      injections; KLF5 increased only after 3 weeks. These results suggested that
      dimethylnitrosamine induced a rapid hepatic fibrogenic response with a possible
      participation of KLF5.

PMID- 18095167
TI  - The differential influence of lexical parameters on naming latencies in German. A
      study on noun and verb picture naming.
AB  - The present study investigates the effects of word category (nouns versus verbs)
      and their subcategories on naming latencies in German, with a focus on the
      influence of lexical parameters on naming performance. The experimental material
      met linguistic construction criteria and was carefully matched for age of
      spontaneous production, frequency, and name agreement. Additional lexical
      parameters (objective age-of-acquisition, word length, visual complexity,
      imageability) were obtained. The results demonstrated a clear effect of word
      category on naming latencies. This effect was supported by two different
      observations. First, there was evidence for category and subcategory effects in
      naming: nouns were named faster than verbs, and intransitive verbs were named
      faster than transitive verbs. Second, while objective age-of-acquisition (naming
      age) turned out to be an important predictor of reaction times for both word
      categories, naming latencies for nouns and verbs were affected differentially by
      other lexical parameters. The results are discussed with respect to current
      controversies on the noun-verb-asymmetry.

PMID- 18095166
TI  - Antidepressant treatment and adherence to combination antiretroviral therapy
      among patients with AIDS and diagnosed depression.
AB  - BACKGROUND: The prevalence of depression is elevated among HIV-infected
      individuals and there is evidence that depression exerts a negative impact on HIV
      medication adherence. METHODS: Merged HIV/AIDS surveillance data and Medicaid
      claims data from January 1996 to December 1998 were used to identify AIDS
      infected patients with diagnosed depression, and filled prescriptions were used
      to identify their antidepressant use, and highly active antiretroviral therapy
      (HAART). Chi-square tests and robust logistic regressions were used to examine
      antidepressant use after HAART initiation, and a person-month approach was used
      to estimate the association between antidepressant treatment and adherence to
      HAART after its initiation. RESULTS: Of the 406 AIDS-infected patients diagnosed
      with depression who initiated HAART during this period, 81% (N = 329) were
      treated with an antidepressant. The HAART adherence rate was low overall. After
      HAART initiation; only 63% of the person-months had a prescription for it.
      However, use of an antidepressant in the prior month was significantly associated
      with HAART in the current month. After controlling for other factors, the odds of
      current-month HAART adherence were increased by almost 30% for those with
      antidepressant use in the prior month (Adjusted OR = 1.28, 95% CI [1.16, 1.41]).
      CONCLUSIONS: While the HAART adherence rate was low among patients with AIDS
      diagnosed with depression, prior month's antidepressant use increases odds of
      adherence. Unmeasured factors may influence the reported association between
      antidepressant use and HAART adherence, but our findings point to the need to
      investigate directly the impact of antidepressant therapy on HAART adherence
      found among patients with AIDS and depression.

PMID- 18095168
TI  - Antiradical capacity and induction of apoptosis on HeLa cells by a Phaseolus
      vulgaris extract.
AB  - Jamapa bean is a black Phaseolus vulgaris variety rich in condensed tannins,
      anthocyanins and flavonols with interesting biological activities. The objective
      of this work was to evaluate the antiradical capacity (ARC) of a Jamapa bean
      methanolic extract (BME) and some of the proanthocyanidin-rich fractions derived
      from it, using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The effect of the
      BME on some proteins involved in apoptosis on HeLa cells was also evaluated. A
      strong correlation between proanthocyanidin concentration in BME and antiradical
      capacity was found, suggesting that these compounds contribute significantly to
      antiradical activity. BME was a better radical scavenger than butylated
      hydroxytoluene (45.6 and 33.9% ARC at 400 microM, respectively). Two
      proanthocyanidin-rich fractions obtained after a preliminary separation of the
      BME using Toyopearl (TP4 and TP6) exhibited a higher antiradical activity than
      the parent extract. The treatment of HeLa cells with 35 microg BME/ml/24 h
      increased the expression of Bax and Caspase-3, pro-apoptotic proteins (6.13 and
      1.2 times for Caspase-3 and Bax, respectively). The mechanism of action of some
      proteins involved in apoptosis was also evaluated, and the results suggest that
      black Jamapa bean could be an important source of polyphenolic compounds with
      potential biological use as antioxidant and anticancer agents.

PMID- 18095169
TI  - Long term, implantable blood pressure monitoring systems.
AB  - An overview of implantable measurement systems suitable for the long-term,
      continuous monitoring of blood pressure is presented in this paper. The
      challenges, design considerations and tradeoffs inherent in these systems are
      overviewed and implantable sensors from both industrial and research environments
      are reviewed. The paper is concluded with an outlook of future directions for
      implantable blood pressure monitoring systems.

PMID- 18095170
TI  - A unifying probabilistic framework for analyzing residual dipolar couplings.
AB  - Residual dipolar couplings provide complementary information to the nuclear
      Overhauser effect measurements that are traditionally used in biomolecular
      structure determination by NMR. In a de novo structure determination, however,
      lack of knowledge about the degree and orientation of molecular alignment
      complicates the analysis of dipolar coupling data. We present a probabilistic
      framework for analyzing residual dipolar couplings and demonstrate that it is
      possible to estimate the atomic coordinates, the complete molecular alignment
      tensor, and the error of the couplings simultaneously. As a by-product, we also
      obtain estimates of the uncertainty in the coordinates and the alignment tensor.
      We show that our approach encompasses existing methods for determining the
      alignment tensor as special cases, including least squares estimation, histogram
      fitting, and elimination of an explicit alignment tensor in the restraint energy.

PMID- 18095171
TI  - Two short questionnaires on leisure-time physical activity compared with serum
      lipids, anthropometric measurements and aerobic power in a suburban population
      from Oslo, Norway.
AB  - The aim was to indirectly validate two short postal questionnaires measuring
      leisure-time physical activity (LPA) by comparing the answers with serum lipids
      and anthropometric measurements. METHODS: All inhabitants aged 31-67 years in two
      suburban, multicultural areas of Oslo, Norway were invited to "Romsas in Motion",
      a community intervention survey, in 2000. Of those, 2950 participants (48%) met
      and were re-invited in 2003. LPA was measured by two short instruments used since
      the 1970s (referred to as the Gothenburg instrument) and since 1994 in Cohort of
      Norway (CONOR). Each instrument was compared with relevant measurements at
      baseline including LPA according to an adapted version of the long International
      Physical Activity Questionnaire (IPAQ-L). In addition, changes during 2000--2003
      in reported LPA were compared with changes in body weight, waist-to-hip ratio,
      lipids and other measurements. RESULTS: LPA measured by the Gothenburg instrument
      correlated weakly, but consistently with relevant biological and anthropometrical
      measurements and with IPAQ-L. The correlation coefficients were -0.1-(-0.2) with
      triglycerides, total-to-high density lipoprotein (HDL)-cholesterol ratio and
      waist-to-hip ratio, around 0.1 with HDL-cholesterol and 0.3 with maximal aerobic
      power. For the CONOR instrument a similar pattern was found in both sexes for the
      hard LPA and in women for light LPA. LPA measured by each short instrument was in
      line with LPA measured with IPAQ-L. CONCLUSIONS: In a multi-linguistic, suburban
      population in Oslo, Norway, LPA measurements by each of two short questionnaires
      were weakly, but consistently correlated with relevant biological and
      anthropometric measurements and strongly with IPAQ-L.

PMID- 18095172
TI  - The Generation R Study Biobank: a resource for epidemiological studies in
      children and their parents.
AB  - The Generation R Study is a population-based prospective cohort study from fetal
      life until young adulthood. The study is designed to identify early environmental
      and genetic causes of normal and abnormal growth, development and health from
      fetal life until young adulthood. In total, 9,778 mothers were enrolled in the
      study. Prenatal and postnatal data collection is conducted by physical
      examinations, questionnaires, interviews, ultrasound examinations and biological
      samples. Major efforts have been conducted for collecting biological specimens
      including DNA, blood for phenotypes and urine samples. In this paper, the
      collection, processing and storage of these biological specimens are described.
      Together with detailed phenotype measurements, these biological specimens form a
      unique resource for epidemiological studies focused on environmental exposures,
      genetic determinants and their interactions in relation to growth, health and
      development from fetal life onwards.

PMID- 18095173
TI  - A cancer incidence survey in Tianjin: the third largest city in China-between
      1981 and 2000.
AB  - During the past three decades, the social/natural environment and lifestyle of
      people in China have undergone a marked transformation to westernization.
      However, age-standardized cancer rates have not been determined to any great
      extent in China. In this study, we tracked the cancer incidence between 1981 and
      2000 in Tianjin, to identify the changes in incidence associated with social and
      economic changes. Cancer incidence data were collected by the Tianjin Cancer
      Registry. Sex, age, and organ site-specific incidence trends were analyzed by the
      "join-point regression" method. Overall crude cancer incidence increased, but the
      age-standardized incidence slightly decreased during the study period. The
      incidence of lung cancer increased between 1981 and 1996 but decreased between
      1996 and 2000. The incidences of uterine, esophageal, stomach, and liver cancers
      decreased. However, the incidences of colorectal, pancreatic, breast, ovarian,
      and prostate cancers all increased during the study period. There was an aging
      related increase in the overall crude cancer incidence and an alteration in the
      distribution of cancer types in Tianjin. The incidences of cancer types that are
      more prevalent in developed countries appeared to increase in China, whereas the
      incidences of cancer types that are more prevalent in developing countries
      appeared to decline.

PMID- 18095175
TI  - Possible autosomal origin of macro B chromosomes in two grasshopper species.
AB  - The acrocentric macro B chromosomes of Rhammatocerus brasiliensis (Acrididae,
      Gomphocerinae) and Xyleus discoideus angulatus (Romaleidae, Romaleinae) are
      highly similar to the X chromosome in each species in terms of morphology, size,
      and pycnosis. However, the results of FISH experiments using 45S and 5S rDNA
      probes suggest that in both species the B chromosomes are most likely of
      autosomal origin. In R. brasiliensis, the B chromosome presented 5S rDNA but not
      45S rDNA, in resemblance to the L(2), L(3), M(5) and S(11) autosomes, but the X
      chromosome lacks both rDNA families. In X. d. angulatus, 45S rDNAs is absent from
      the B chromosome, whereas the X chromosome contains one of the two 45S rDNA
      clusters in the genome. The occurrence of B chromosomes in all nine R.
      brasiliensis populations analyzed indicates that they are widely distributed in
      Northeastern Brazil, and the small amount of interpopulation variation found for
      B chromosome prevalence suggests the existence of high gene flow, presumably due
      to the abundance of this grasshopper species on several types of vegetation and
      its relatively high flight capability.

PMID- 18095178
TI  - Simulation of impact of oil spill in the ocean--a case study of Arabian Gulf.
AB  - To meet the growing energy demand worldwide, oil and gas exploration and
      production activities have increased rapidly both in onshore and offshore areas.
      The produced oil from the ocean bed is transported onshore either by ship or
      pipeline. This has increased the risk of oil spill in the coastal area. In order
      to prepare an emergency preparedness plan and to assess the magnitude of risk
      involved in transporting and offloading oil, oil spill simulation studies play an
      important role. This paper describes a simulation of oil spill in coastal bay of
      Arabian Gulf where new developments are taking place using MIKE 21 model. The
      developments include a diesel based thermal power plant near Sir Baniyas Island,
      which is an ecological fragile area. Based on the project activity, two probable
      scenarios, one for diesel leak (250 m3/h) for 1 h and the other for instantaneous
      spill (500 m3) are considered. The MIKE 21 model was calibrated for hydrodynamics
      using measured field data followed by diesel-spill simulation to track its
      movement in the Arabian Gulf. The results for both leak and instantaneous spill
      indicate that spilled diesel will not move towards the Sir Banyas Island and more
      than 45% of the diesel will be evaporated within 48 h of oil spill. Based on the
      results, a clean up and contingency plan is proposed to mitigate the adverse
      impacts arising due to diesel spill in the study area.

PMID- 18095176
TI  - Localized co-transcriptional recruitment of the multifunctional RNA-binding
      protein CELF1 by lampbrush chromosome transcription units.
AB  - The highly-extended transcription units of lampbrush chromosomes (LBCs) offer
      unique opportunities to study the co-transcriptional events occurring on nascent
      transcripts. Using LBCs from amphibian oocytes, I investigated whether CELF1, an
      RNA binding protein involved in the regulation of alternative splicing, mRNA
      stability and translation, is localized to active transcription units. Antibodies
      raised against mammalian (CUG-BP1) and amphibian (EDEN-BP) CELF1 were used to
      immunostain LBC spreads prepared from several species, including Xenopus laevis
      and the axolotl Ambystoma mexicanum. Up to about 50 separate LBC loci were
      convincingly immunostained and it was clear that CELF1 was present in the nascent
      RNPs of lateral loops. Furthermore, myc-tagged CUG-BP1 expressed in microinjected
      axolotl oocytes was specifically targeted to nascent transcripts of loops that
      recruit endogenous CELF1. In many active transcription units CELF1 was distinctly
      localized, being first recruited by nascent transcripts only far downstream of
      the transcription start site and remaining associated until the end of
      transcription. Overall it appears possible that the multiple functions of CELF1
      in regulating posttranscriptional gene expression could all be predetermined
      during transcription by virtue of a region-specific binding to the nascent
      transcripts of target genes.

PMID- 18095177
TI  - Chromosome homology between mouse and three Muridae species, Millardia meltada,
      Acomys dimidiatus and Micromys minutus, and conserved chromosome segments in
      murid karyotypes.
AB  - Comparative chromosome painting with mouse (Mus musculus, MMU) chromosome
      specific DNA probes was performed for three Muridae species, the Indian soft
      furred field rat (Millardia meltada), the spiny mouse (Acomys dimidiatus) and the
      harvest mouse (Micromys minutus). All probes except for the Y probe were
      successfully hybridized to the chromosomes of all species, and homologous
      chromosome segments between mouse and the three species were identified at the
      molecular level. Comparison of our data with the published data of six other
      genera (Mus, Rattus, Apodemus, Otomys, Rhabdomys and Cricetulus) of the Muridae
      suggested that the associations MMU1b/17a, 2b/13a, 5b/11a, 7/19, 10b/17b,
      10c/17c, 11b/16a, 12/17d and 13b/15, and the single painted chromosomes and
      chromosome segments MMU3, 4, 5a, 8a, 8b, 16b, 18 and X were probably contained by
      the ancestral karyotype of the Muridae, and have been strongly conserved
      throughout murid evolution.

PMID- 18095179
TI  - Salmonella mutagenicity analysis of water samples from Camalti Saltern.
AB  - Mutagenicity analysis of water samples from Camalti Saltern, Turkey were
      investigated by applying Salmonella mutagenicity test. Plate incorporation assay
      was applied in the absence of metabolic activation. XAD 4 and XAD 16 columns were
      used for the fractionation of the water samples. The results obtained were
      negative in both TA 98 and TA 100. Although the number of revertants of XAD 16
      extract in station B were higher than the revertants in the other stations for TA
      98 strain when compared to the solvent control. However this was not significant
      to be considered as mutagenic. The results were discussed for the future
      analysis.

PMID- 18095180
TI  - Development and application of an integrated indoor air quality audit to an
      international hotel building in Taiwan.
AB  - Indoor air quality (IAQ) has begun to surface as an important issue that affects
      the comfort and health of people; however, there is little research concerned
      about the IAQ monitoring of hotels up to now. Hotels are designed to provide
      comfortable spaces for guests. However, most complaints related to uncomfortable
      thermal environment and inadequate indoor air quality appear. In addition,
      microbial pollution can affect the health of tourists such as the Legionnaire's
      disease and SARS problems. This study is aimed to establish the comprehensive IAQ
      audit approach for hotel buildings with portable equipment, and one five-star
      international hotel in Taiwan was selected to exam this integrated approach.
      Finally, four major problems are identified after the comprehensive IAQ audit.
      They are: (1) low room temperature (21.8 degrees C), (2) insufficient air
      exchange rate (<1.5 h(-1)), (3) formaldehyde contamination (>0.02 ppm), and (4)
      the microbial pollution (total bacteria: 2,624-3,799 CFU/m(3)). The high level of
      formaldehyde may be due to the emission from the detergent and cleaning agents
      used for housekeeping.

PMID- 18095181
TI  - Assessment of groundwater vulnerability in the coastal region of Oman using
      DRASTIC index method in GIS environment.
AB  - A study was carried out to develop a vulnerability map for Barka region in the
      North Batina of Oman using DRASTIC vulnerability index method in GIS environment.
      DRASTIC layers were created using data from published reports and the seven
      DRASTIC layers were processed by the ArcGIS geographic information system.
      Finally, DRASTIC maps were created for 1995 and 2004 to understand the long-term
      changes in the vulnerability index. DRASTIC vulnerability maps were evaluated
      using groundwater quality data such as chemical and biological parameters.
      DRASTIC vulnerability maps of 1995 and 2004 indicate that the northern part of
      Barka is more vulnerable to pollution than southern part and the central part of
      Barka also shows high relative vulnerability which is mostly related to the high
      conductivity values. Moreover, the changes in water level due to high abstraction
      rate of groundwater reflect in the vulnerability maps and low vulnerability area
      is increased in the southern part during 2004 compared to 1995. Moreover,
      regional distribution maps of nitrate, chloride and total and fecal coliforms are
      well correlated with DRASTIC vulnerability maps. In contrast to this, even though
      DRASTIC method predicted the central part of the study region is highly
      vulnerable, both chemical and biological parameters show lower concentrations in
      this region compared to coastal belt, which is mainly due to agricultural and
      urban development. In Barka, urban development and agricultural activities are
      very high in coastal region compared to southern and central part of the study
      area. Hence, this study concluded that DRASTIC method is also applicable in
      coastal region having ubiquitous contamination sources.

PMID- 18095182
TI  - Concentrations of Cr, Cd, Cu, Zn and Fe in crab Charybdis longicollis and shrimp
      Penaeus semisulcatus from the Iskenderun Bay, Turkey.
AB  - Copper, chromium cadmium, iron and zinc concentrations were determined in marine
      crab Charybdis longicollis and marine shrimp Penaeus semisulcatus in order to
      assess the impact of industrial activities and the sinking of M/V Ulla ship.
      Liver, gill and muscle sample solutions prepared analyzed using the atomic
      absorption spectrophotometry technique. The order of the metal concentrations
      found in muscle of crab was: Cu>Cr>Fe>Zn>Cd, while in muscle of shrimp the order
      was different: Cr>Cu>Zn>Fe>Cd. The highest Cu, Cr, Cd, Fe and Zn concentrations
      were found in the liver, and this was followed by the gill and muscle in both
      species. The levels of all metals in a given tissue were always higher in C.
      longicollis than in P. semisulcatus. Metals in both species show seasonal
      variations. In both species the highest concentrations were detected for all
      metals in summer.

PMID- 18095183
TI  - Psychological determinants of the intention to educate patients about
      benzodiazepines.
AB  - OBJECTIVE: General practitioners and pharmacists do not properly educate their
      patients about the disadvantages of benzodiazepines. In order to increase and
      improve education, this study will investigate which psychological factors (i.e.,
      beliefs, outcome expectation, social norm and self-efficacy) predict the
      intention to educate. METHODS: A cross-sectional survey study was conducted in
      which 339 general practitioners and 149 pharmacists in the Netherlands completed
      a questionnaire. RESULTS: The Results show that the above-mentioned factors play
      an important role in forming intentions to educate. However, differences exist
      between general practitioners and pharmacists. CONCLUSION: General practitioners
      and pharmacists intend to educate in cases where they think that benzodiazepines
      have well-defined disadvantages, when the education they undertake leads to
      success, when they feel pressure to educate from their surroundings and when they
      are capable of educating. Implications for practice These findings contribute to
      a better understanding of patient education and are of great value in developing
      new interventions to improve education.

PMID- 18095184
TI  - Leslie Orgel 1927-2007.

PMID- 18095185
TI  - Pancreatic calcification in a patient with homocystinuria.

PMID- 18095186
TI  - Validation of the Japanese version of EORTC QLQ-CR38.
AB  - PURPOSE: The objective of this study was to test the reliability and validity of
      the Japanese version of the European Organization for Research and Treatment of
      Cancer (EORTC) Colorectal Cancer-Specific Quality of Life Questionnaire (QLQ
      CR38). METHODS: The questionnaire was tested among 109 colorectal cancer patients
      on several occasions. The timing was prior to treatment with radiotherapy or
      chemotherapy, during treatment and 3 months following the second assessment. For
      purpose of test-retest reliability, a subgroup of patients completed the QLQ-CR38
      1 week following the third assessment. RESULTS: Multitrait scaling analysis
      confirmed the hypothesised scale structure of both the function scales and the
      symptom scales except female sexual problem scale. Cronbach's alpha coefficients
      for seven of the nine scales exceeded the 0.7 criterion at one or both
      assessments. The test-retest reliability for all scales except three symptom
      scales was 0.67 or higher. On the basis of known-groups comparisons, four of 46
      comparisons distinguished between patients differing in disease stage, initial
      and on-treatment performance status and presence or absence of a stoma.
      Additionally, these scales detected change over time as a function of change in
      performance status and treatment-induced change. CONCLUSION: These preliminary
      results suggest that the Japanese EORTC QLQ-CR38 may be a reliable and valid
      supplementary measure of quality of life in colorectal cancer patients.

PMID- 18095187
TI  - Computational prediction of protein-protein interactions.
AB  - Recently a number of computational approaches have been developed for the
      prediction of protein-protein interactions. Complete genome sequencing projects
      have provided the vast amount of information needed for these analyses. These
      methods utilize the structural, genomic, and biological context of proteins and
      genes in complete genomes to predict protein interaction networks and functional
      linkages between proteins. Given that experimental techniques remain expensive,
      time-consuming, and labor-intensive, these methods represent an important advance
      in proteomics. Some of these approaches utilize sequence data alone to predict
      interactions, while others combine multiple computational and experimental
      datasets to accurately build protein interaction maps for complete genomes. These
      methods represent a complementary approach to current high-throughput projects
      whose aim is to delineate protein interaction maps in complete genomes. We will
      describe a number of computational protocols for protein interaction prediction
      based on the structural, genomic, and biological context of proteins in complete
      genomes, and detail methods for protein interaction network visualization and
      analysis.

PMID- 18095189
TI  - Cell adhesion molecules: potential therapeutic & diagnostic implications.
AB  - The role of cell adhesion molecules (CAM) and extracellular matrix proteins (ECM)
      in various pathological processes including angiogenesis, thrombosis, apoptosis,
      cell migration & proliferation are well documented. These processes can lead to
      both acute and chronic disease states such as ocular diseases, metastasis,
      unstable angina, myocardial infarction, stroke, osteoporosis, a wide range of
      inflammatory diseases, vascular remodeling, and neurodegenerative disorders. A
      key success in this field is evident from the potential role of the platelet
      GPIIb/IIIa integrin in the prevention and diagnosis of various thromboembolic
      disorders. Additionally, the use of soluble adhesion molecules as potential
      diagnostic markers for acute and chronic leukocyte, platelet, and endothelial
      cellular insult are increasingly utilized. The development of various therapeutic
      and diagnostic candidates based on the key role of CAM, with special emphasis on
      integrins in various diseases as well as the structure-function aspects of cell
      adhesion and signaling of the different CAM and ECM are highlighted.

PMID- 18095188
TI  - Validation and quality control of protein microarray-based analytical methods.
AB  - Protein microarray technology is used mainly in the research laboratory and it is
      being used to uncover important diagnostic and prognostic markers that may one
      day emerge as routine clinical laboratory tests. It is important that these
      methods are subject to control procedures, in order to ensure that data of the
      highest quality are obtained. If quality is not controlled, the assay may yield
      erroneous results that would mask or confound meaningful diagnostic or prognostic
      associations. This chapter surveys the range of strategies designed to assure the
      analytical quality of protein microarray methods and it also highlights some of
      the potential pitfalls when moving these arrays into routine clinical practice.
      With the development of appropriate quality control and assurance measures, we
      anticipate protein microarray-based assays will be of substantial benefit in the
      future practice of laboratory medicine.

PMID- 18095190
TI  - Development of an efficient protocol of RNA isolation from recalcitrant tree
      tissues.
AB  - Isolation of RNA from recalcitrant tree tissues has been problematic due to large
      amounts of secondary metabolites and interfering compounds in their cells. We
      have developed an efficient RNA extraction method, which yielded high-quality RNA
      preparations from tissues of the lychee tree. The method reported here utilized
      EDTA, LSS, and CTAB to successfully inhibit RNase activities. It was found that a
      high ionic strength brought about by 2 M NaCl was necessary. In addition,
      secondary metabolites and other interfering compounds were effectively removed
      using sodium borate and PVPP under a deoxidized condition. The quality of
      purified RNA was tested by both RACE and Northern blotting analysis, ensuring
      that the RNA could be used for subsequent gene expression analysis. This method
      has been successfully applied to purify RNA from 15 other plant species. In
      conclusion, the protocol reported here is expected to have excellent applications
      for RNA isolation from recalcitrant plant tissues.

PMID- 18095191
TI  - Evaluation of two set of primers for detection of immediate early gene UL123 of
      human cytomegalovirus (HCMV).
AB  - Human cytomegalovirus (HCMV) is a widespread agent causing a life-long persistent
      and generally asymptomatic infection in immunocompetent individuals. In contrast,
      immunocompromised subjects are the most susceptible group to experience HCMV
      disease. First genes to be expressed during the replication cycle are the
      immediate early (IE) genes, the products of which have pleiotropic effects on
      host cell metabolism. Aim of this study was to compare two set of primers in the
      optimization and standardization of a RT-PCR assay for qualitative detection of
      mRNA encoded by the IE gene UL123 (IE1). The RT-PCR assays were then used to
      evaluate the UL123 gene expression in 29 peripheral blood leukocyte (PBL) samples
      obtained from 14 renal transplant recipients. In particular, 21/29 (72.4%) were
      positive with set A of primers vs. 24/29 (82.8%) with set B. Only one sample were
      negative with set B and positive with set A. Twenty-four of 29 samples (82.8%)
      were pp65-antigaenemia positive: 21 mRNA-UL123 positive with set A vs. 22 with
      set B; all viraemia-positive patients were mRNA-UL123 positive with both set A
      and B. Five of 29 samples were pp65-antigaenemia negative: 1 mRNA-UL 123 positive
      with set A vs. 2 with set B; all of them were viraemia-negative. These two RT-PCR
      assays could provide a reliable, rapid and sensitive system enabling the
      detection and identification of UL123 transcripts and could be usefully employed
      to study the pathogenesis of HCMV-related diseases.

PMID- 18095193
TI  - [Neuropathic pain].
AB  - Neuropathic pain is caused by functional abnormalities of structural lesions or
      dysfunction in the peripheral or central nervous system, and occurs without
      peripheral nociceptor stimulation. Neuropathic pain has a great impact on the
      quality of life. Majority of the patients are unable to maintain an independent
      lifestyle due to their moderate to severe chronic pain and often depression
      contributes to the illness. Many common diseases, such as stroke, multiple
      sclerosis and syringomyelia may produce neuropathic pain. Neuropathic pain is a
      complex disease, involving several molecular pathways. Neuropathic pain treatment
      is stil extremely difficult despite our knowledge about this difficult to
      diagnose and treat pain condition has improved a lot with the aid of recent
      experimental and clinical studies. This review summarizes the underlying
      mechanisms, diagnosis and treatment approaches based on different mechanisms of
      effect.

PMID- 18095194
TI  - [Gamma knife radiosurgery for treatment of pain].
AB  - Radiosurgery is to irradiate the small volume targets inside of the cranium with
      high dose radiation in a single session. Gamma knife radiosurgery has been in use
      for treatment of pain many years. The first cases which have been treated with
      radiosurgery technique were trigeminal neuralgia patients. After the first
      installment of gamma knife in 1968, it has been used for thalamotomy in cancer
      pain. Nowadays the main indication for gamma knife radiosurgery for pain is
      trigeminal neuralgia.

PMID- 18095192
TI  - A comparison of hybridization efficiency between flat glass and channel glass
      solid supports.
AB  - Two different solid supports, channel glass and flat glass, were compared for
      their affect on the sensitivity and efficiency of DNA hybridization reactions.
      Both solid supports were tested using a set of arrayed, synthetic
      oligonucleotides that are designed to detect short insertion/deletion
      polymorphisms (SIDPs). A total of 13 different human SIDPs were chosen for
      analysis. Capture probes, designed for this test set, were covalently immobilized
      on substrates. Hybridization efficiency was assessed using fluorescently labeled
      stacking probes which were preannealed to the target and then hybridized to the
      support-bound oligonucleotide array; the hybridization pattern was detected by
      fluorescence imaging. It was found that structural features of nucleic acid
      capture probes tethered to a solid support and the molecular basis of their
      interaction with targets in solution have direct implications on the
      hybridization process. Our results demonstrate that channel glass has a number of
      practical advantages over flat glass including higher sensitivity and a faster
      hybridization rate.

PMID- 18095195
TI  - [Pediatricians' and pediatric nurses' knowledge about pain in newborn infants and
      their practices in some provinces in Turkey].
AB  - This research was conducted as a descriptive study for the purpose of determining
      the status of pediatricians and nurses who work on pediatric wards about their
      recognizing, evaluating, and using appropriate nonpharmacologic interventions to
      treat pain in newborn infants. The study was conducted between March and May
      2005. A total of 198 nurses and physicians were included in the sample, 31 of
      whom were from Sivas 1st Izzettin Keykavus State Hospital, 76 from Akdeniz
      University Medical Faculty Hospital, 45 from Mersin University Medical Faculty
      Research, Mersin State and Taurus State Hospitals and 46 from Ege University
      Medical Faculty Hospital. The data were collected using a 16-question survey
      form. Five of the survey questions were regarding the nurses' and physicians'
      sociodemographic characteristics and 11 contained questions directed at obtaining
      physicians and nurses' information about pain in newborns. The results of the
      research showed that the physicians and nurses were knowledgeable about newborn
      pain. It was determined that the pediatric nurses used nonpharmacologic methods
      during invasive procedures in the newborns but the physicians did not. In
      conclusion it is recommended that this issue receive more discussion in
      continuing education programs at hospitals for the purpose of encouraging nurses
      and physicians to use nonpharmacologic methods during invasive procedures that
      are done in newborns to facilitate a multidisciplinary team approach for pain
      management in newborn infants.

PMID- 18095196
TI  - [The postoperative analgesic effects of magnesium infusion on brachial plexus
      block].
AB  - Magnesium sulphate infusion decreases analgesic requirements after general
      anesthesia. Aim of this study was to assess the effects of postoperative
      magnesium infusion for 24 hours on duration of the block, sedation and
      postoperative analgesic consumption after brachial plexus block. After obtaining
      approval from local ethic committee, 70 ASA class I and II patients were included
      to the randomised double blind study. Brachial plexus block was performed using
      axillary approach with lignocaine 1.25% adrenaline 1/200 000 40 ml. Groups
      received 5 mg/kg bolus and 500 mg/h magnesium sulphate infusion or saline
      controls at the same volume during 24 hour. Analgesia and sedation were assessed
      while determining time to first pain and rescue analgesic, time to regain motor
      capability, visual analogue scale and sedation scores for every 4 hour during
      postoperative 24 h. period. While time to first pain and rescue analgesic was
      increased, total analgesic consumption was reduced significantly on magnesium
      infusion group (Meperidine: C: 36.3 +/- 42.6 mg, Mg: 11.7 +/- 12.2 mg, p: 0.001).
      Visual analogue scales were also observed to be lower in all periods. Time to
      motor block resolution, and sedation scores were similar. Magnesium sulphate
      infusion is thought as a safe and suitable adjunct for reducing analgesic
      consumption and possible complications without interfering daily activity in
      patients undergoing brachial plexus block.

PMID- 18095197
TI  - [Effect of preoperative 900 and 1200 mg single oral dose of gabapentin on
      postoperative pain relief and tramadol consumption in open cholecystectomy
      surgery].
AB  - In this study, the effects of preoperative 900 and 1200 mg single dose of
      gabapentin on postoperative pain relief and tramadol consumption in elective open
      cholecystectomies were investigated. Fourty-five ASA I-II patients were randomly
      divided into three groups. Group I was control group and patients in group II and
      III received 900 mg or 1200 mg gabapentin 1 hour before the operations
      respectively. All patients received intravenous tramadol at the end of surgery
      via a patient controlled analgesia (PCA) device. Pain scores were evaluated at
      the recovery room (0),1, 2, 3, 4, 6, 8, 12 and 24h postoperatively at rest and
      movement, using a 10 cm VAS. In the recovery room, VAS scores at rest were three
      times less (1,4+/-0.6 versus 4,9+/-1.0 and 4.4+/-1.1), and visual analogue scale
      (VAS) scores at movement were two times less (3.4+/-1.0 versus 6.8+/-1.8 ve 6.1+/
      1.6) in group III when compared to group I and II respectively. Mean loading
      doses were significantly lower in group III (28.3+/-8.7) than group I (66.6+/
      20.4) and II (61.6+/-20.8). VAS scores at rest during the postoperative first 6h
      and at movement during the postoperative first 8h were significantly lower in
      group III than group I and II. Total tramadol consumption was lower in group III
      (240.4+/-31.0), than group I (456.0+/-35.5) and group II (438.7+/-35.0).
      Additional meperidine was necessary for two patients both in groups I and II,
      although none of the patients needed in group III. Higher patient satisfaction
      scores were obtained in group III. Adverse effect incidences were higher in group
      I and II than in group III. As a result, we believe that to improve analgesic
      quality after open cholecystectomy, preoperative single dose of gabapentin should
      at least be 1200 mg.

PMID- 18095198
TI  - Usage of remifentanil and fentanyl in intravenous patient-controlled sedo
      analgesia.
AB  - Our aim was to investigate the effects of patient-controlled sedo/analgesia with
      fentanyl or remifentanil during cataract surgery with phacoemulsification method
      under topical anaesthesia. The ethical committee has approved the prospective,
      randomized, double-blind study. ASA I-III, 120 patients underwent cataract
      surgery were randomly allocated to 3 groups. Fentanyl was administered in 0.7
      microg/kg loading, 10 microg bolus dose with 5 minutes lockout time, remifentanil
      was administered 0.3 microg/kg loading, 20 microg bolus dose with 3 minutes
      lockout time by patient controlled analgesia (PCA) equipment. In the control
      group, saline solution was given without any analgesic drug. Cardiorespiratory
      system findings, verbal pain scale and sedation scores were recorded
      preoperatively and intraoperatively at the 5th, 10th, 15th, 20th and 30th
      minutes. Discomfort during surgery, pressing the PCA button, and complications
      were recorded. The verbal pain scale scores was significantly lower in the drug
      groups than the those in control group at the 15th minute. The sedation scores
      was significantly higher in the remifentanil group at the 5th minute (p=0.019)
      and in the fentanyl group at the 10th minute (p=0.007) than those in the control
      group. The number of patients pressing the PCA button was much higher in the
      control group than the drug groups (p<0.05). Patient comfort and surgeon
      satisfaction were higher in the drug groups (p<0.05). Intravenous-PCA
      sedo/analgesia addition to topical anaesthesia provides an advantage in
      sedo/analgesia, patient comfort, and surgeon satisfaction. PCA is a convenient
      and safe method, especially at the beginning of the operation when anxiety is
      intense, and during healon/lens implantation.

PMID- 18095199
TI  - Neurofeedback in fibromyalgia syndrome.
AB  - EEG Biofeedback (Neurofeedback-NFB) is a learning strategy that enables people to
      alter their brainwaves. In the present case study, we applied a NFB protocol on
      three patients with Fibromyalgia Syndrome (FMS). The existing symptoms and
      clinical conditions of the patients attributed to FMS, Visual Analog Scale for
      pain and fatigue, Hamilton Depression and Anxiety Inventory Scales, Beck
      Depression and Anxiety Inventory Scales, and SF-36 were recorded before and after
      NFB training. Most of the symptoms were decreased after ten sessions. There was
      also improvement in all of the scales after the treatment. The results of the
      present study may suggest NFB training as a novel treatment method in FMS.

PMID- 18095200
TI  - Neuropathic arthropathy caused by syringomyelia in different joints and lesion of
      brachial plexus at right upper extremity: a case report.
AB  - Syringomyelia is characterized by slow progression; the joints involved most
      frequently are the shoulders and elbows. Neuropathic arthropathy of the hand is
      quite rare. Herewith, we present a case of neuropathic arthropathy (NA) of the
      joints in the upper limb secondary to Syringomyelia. Atypical features of the
      case included NA of the shoulder, elbow and metacarpophalengeal joint in the same
      upper limb. These atypical features superimposed shoulder subluxation and
      brachial plexopathy which diagnosed by electrophysiologic studies. To the best of
      our knowledge, our study is the first of its kind that reports a patient who had
      all the above mentioned symptoms in the same upper limb.

PMID- 18095201
TI  - [Physicians' health: myths, reality and visions].

PMID- 18095202
TI  - [Quality of life for physicians and women physicians. Experiences from empirical
      research].

PMID- 18095203
TI  - [Dependency diseases of physicians and women physicians. Specific treatment
      options make possible a successful therapy].

PMID- 18095204
TI  - [Extensive pleural empyema with mediastinal invasion].

PMID- 18095205
TI  - [Health of female physicians].

PMID- 18095206
TI  - [Working conditions and depression in physicians].

PMID- 18095207
TI  - [Physicians as patients--physicians treating other physicians].

PMID- 18095208
TI  - ["Physician heal yourself"--doctors as patients].

PMID- 18095209
TI  - [The diagnostic lumbar puncture].

PMID- 18095210
TI  - [Damage assessment claim of a chief physician against hospital insurance carriers
      because of the conclusion of an ineffective elective service agreement. Decision
      of the Bavarian Administrative Court from November 2, 2006].

PMID- 18095212
TI  - [Correlated C-reactive protein and calcification inhibitors in hemodialysis
      patients with cardiovascular parameters and risk factors? About the article in
      DMW 36/2007].

PMID- 18095213
TI  - [The determination of emotional resource potentials--psychometric analysis of a
      test for the assessment of individual emotional experiencing].
AB  - We introduce a test for the assessment of individual emotional resources (BER).
      The BER can be used to induce positive emotional experiences in both an
      individual and group setting. These experiences are then in a second step rated
      by the individuals in terms of their immediate intensity as well as their
      occurrence in everyday life. We examined the psychometric properties of the BER
      in a non-clinical student sample (n = 614) and a clinical sample of psychotherapy
      inpatients (n = 164). Reliabilities ranged from 0.75 to 0.89 (internal
      consistency) and 0.68 to 0.71 (retest). Neither age or gender, nor group size
      were related to the BER scores. Some empirical support was found for the expected
      two factorial structure. The correlations of the BER with related psychological
      constructs and the comparison of non clinical and clinical scores indicate good
      convergent and discriminant validity. According to the correlational analyses,
      emotional experiences induced by the BER seem not to be activated via direct
      hypnotic induction. They rather seem to be connected to an individual's
      capability of mental imagery. Implications of this novel approach for the
      assessment of emotional resources in research and clinical practice are
      discussed.

PMID- 18095214
TI  - Antepartum risk factors associated with peripartum cesarean hysterectomy in women
      with placenta previa.
AB  - The objective of this study was to identify antepartum risk factors for
      peripartum hysterectomy in women with placenta previa. The medical records of
      women with placenta previa who underwent cesarean section (C/S) were reviewed
      retrospectively. Data regarding the reproductive history and peripartum outcomes
      were analyzed. Multivariable analysis was used to identify factors independently
      associated with hysterectomy. During an 8.5-year period, 346 cases of placenta
      previa were identified in 24,987 deliveries (1.4%). An emergent hysterectomy was
      performed in 31 patients (9.0%). Multiparity, total previa, history of abortion,
      C/S, and placenta previa was more common in the hysterectomy group. An increasing
      number of abortions and C/S were associated with a higher frequency of
      hysterectomy. By the multivariable analysis, previous abortion, previous C/S, and
      total previa were significant risk factors for hysterectomy. We concluded that in
      women with placenta previa, history of abortion as well as prior C/S, and a total
      previa are strong antepartum risk factors for peripartum hysterectomy.

PMID- 18095215
TI  - Sildenafil use in a symptomatic neonate with severe Ebstein's anomaly of the
      tricuspid valve.
AB  - Ebstein's anomaly (EA) is associated with poor outcome in symptomatic neonates.
      Management typically includes prostaglandins or surgical creation of a Blalock
      Taussig shunt. Right ventricular afterload reduction may help by improving the
      forward flow across the pulmonary valve. We report the successful use of oral
      sildenafil, a pulmonary vasodilator, in a neonate with severe EA.

PMID- 18095216
TI  - Endothelial NO-synthase intron 4 polymorphism is associated with disturbed in
      vivo nitric oxide production in individuals prone to type 2 diabetes.
AB  - Insulin resistance, as well as vascular disease, both share a relevant genetic
      background taking the influence of a positive family history of these disorders.
      On the other hand, insulin resistance is associated with a proatherosclerotic
      disturbance in nitric oxide dependent vasodilation, probably contributing to the
      link between these two disorders. We examined the association between nitric
      oxide dependent vasodilation (measured with high resolution ultrasound at 13 MHz)
      and three relevant NO-synthase (eNOS)-polymorphisms in 200 insulin resistant
      subjects participating in the Tuebinger Lifestyle Intervention Program (TULIP).
      This study revealed that carriers of the eNOS intron 4 polymorphism (aa 2.16%; ab
      24.2%; bb 73.2%) show significantly worse endothelial, and thereby eNOS dependent
      vasodilation (p=0.03, multivariate ANOVA), as compared to wildtype carriers. The
      5' UTR T-786C and the G894 T polymorphism did not show any influence on eNOS
      activity. In subjects at increased risk to develop type 2 diabetes, the eNOS
      intron 4 polymorphism is independently associated with endothelial function as
      indicated by disturbed endothelial NO production. Due to the high prevalence and
      the relatively strong effect, this polymorphism might help to identify subjects
      at increased risk for atherosclerosis associated with overweight and insulin
      resistance.

PMID- 18095217
TI  - Production stability of active polysaccharides of Dendrobium huoshanense using
      long-term cultures of protocorm-like bodies.
AB  - In this study, the production stability of active polysaccharides in protocorm
      like bodies (PLBs) induced from the seedling segments of Dendrobium huoshanense
      C. Z. Tang et S. J. Cheng was investigated during long-term subculture.
      Subcultures were conducted once every 30 days. With an average inoculum of 39 g/L
      fresh PLBs, the increase in biomass ranged from 95.7 g/L to 103.9 g/L in fresh
      weight and 3.2 g/L to 3.4 g/L in dry weight during eighteen continuous
      subcultures while polysaccharide content in PLBs was from 0.8 mg/g Fw (mg
      polysaccharide per gram PLBs in fresh weight) to 1.0 mg/g Fw. In addition,
      polysaccharides from all cultures showed a similar potential of stimulating
      interferon gamma (IFN-gamma) release in the supernatant of splenocytes and tumor
      necrosis factor alpha (TNF-alpha) release in the supernatant of peritoneal
      macrophages. To elucidate the genetic basis of polysaccharide production
      stability in long-term subculture of PLBs, the genetic fingerprints by RAPD were
      further analyzed using plantlets from PLB development. Results showed that there
      is no evidence of genetic variation both within the plantlets from the different
      subcultures of PLBs and between long-term subcultures and the donor plants.

PMID- 18095218
TI  - Modulation of GABAA receptors by valerian extracts is related to the content of
      valerenic acid.
AB  - Valeriana Officinalis L . is a traditionally used sleep remedy, however, the
      mechanism of action and the substances responsible for its sedative and sleep
      enhancing properties are not fully understood. As we previously identified
      valerenic acid as a subunit-specific allosteric modulator of GABAA receptors, we
      now investigated the relation between modulation of GABAA receptors by Valerian
      extracts of different polarity and the content of sesquiterpenic acids (valerenic
      acid, acetoxyvalerenic acid). All extracts were analysed by HPLC concerning the
      content of sesquiterpenic acids. GABAA receptors composed of alpha 1, beta 2 and
      gamma 2S subunits were expressed in Xenopus laevis oocytes and the modulation of
      chloride currents through GABAA receptors (IGABA) by Valerian extracts was
      investigated using the two-microelectrode voltage clamp technique. Apolar
      extracts induced a significant enhancement of IGABA, whereas polar extracts
      showed no effect. These results were confirmed by fractionating a highly active
      ethyl acetate extract: again fractions with high contents of valerenic acid
      exhibited strong receptor activation. In addition, removal of sesquiterpenic
      acids from the ethyl acetate extract led to a loss of I (GABA) enhancement. In
      conclusion, our data show that the extent of GABAA receptor modulation by
      Valerian extracts is related to the content of valerenic acid.

PMID- 18095219
TI  - Estrogenic activities of isoflavones and flavones and their structure-activity
      relationships.
AB  - In this study, we assessed the relationships between the structure and
      estrogenicity of flavonoid derivatives. We evaluated estrogenicity via yeast
      transactivation assays, E-screen assays, and ER binding assays. Genistein and
      coumestrol in the yeast transactivation assay and biochanin A, genistein, and
      equol in the E-screen assay, have been shown to have profound estrogenic
      activities. Flavonoids, with the exception of biochanin A and daidzein, exhibit
      more profound selectivity for ER beta than for ER alpha. We compared several
      flavonoids in terms of estrogenicity, as well as relatively small structural
      differences including the position of the phenol ring and hydroxy groups, the
      substitution of hydroxy groups or methoxy groups, the opening of the phenol ring;
      glycitein vs. 4',6,7-trihydroxyisoflavone, biochanin A vs. genistein, apigenin
      vs. genistein, 7,4'-dihydroxyflavone vs. isoliquiritigenin. A quantitative
      structure-activity relationship study design was utilized to develop model
      equations for the estrogenic activities of flavonoid derivatives. The prediction
      of estrogenicity with regard to ER alpha shows a positive correlation with MW and
      AlogP, and a negative correlation with Apol and Area (r2 = 0.89 and q2 = 0.83).
      The prediction of estrogenicity with regard to ER beta reveals a positive
      correlation with the AlogP and Hbond acceptors, and a negative correlation with
      RadOfGyration (r2 = 0.77 and q2 = 0.72).

PMID- 18095221
TI  - Optimizing use of beta-lactam antibiotics in the critically ill.
AB  - The escalation of serious infections in critically ill patients over the past 25
      years has continued despite advances in contemporary medicine. Ongoing research
      to reduce the high morbidity and mortality rates is mandated. beta-lactam
      antibiotics are often used empirically in serious infections. The efficacy of
      these time-dependent antibiotics is correlated with the time that concentrations
      are maintained above the minimum inhibitory concentration of the infective
      pathogen. In critically ill patients, pathophysiological changes can reduce
      antibiotic concentrations and thus alternative modes of administration such as
      continuous infusion have been studied and shown to standardize beta-lactam
      pharmacokinetics and meet pharmacodynamic targets. Clinical data supporting the
      efficacy of continuous infusion are currently scarce, but data continue to grow.
      Likewise antibiotic resistance continues to grow. Recent data suggest that poor
      dosing strategies may be contributing to this problem, which is exacerbated by a
      lack of development of alternate antibiotics. Suffice to say clinicians must use
      antibiotic regimens that optimally treat the individual patient and reduce the
      development of antibiotic resistance.

PMID- 18095222
TI  - Optimizing use of quinolones in the critically ill.
AB  - Fluoroquinolones (FQs) are broad spectrum, concentration dependent, bactericidal
      antimicrobials that have been commonly utilized to treat severe nosocomial
      infections. FQ activity is derived from their ability to inhibit DNA gyrase and
      topoisomerase IV; resistance has been shown to develop in target site mutations,
      alterations in efflux pump systems, and incorporation of plasmids. The
      probability of preventing emergence of resistance and achieving maximal rates of
      kill are best related to the ratio of free-drug in the area under the
      concentration-time curve (AUC) to minimum inhibitory concentration (AUC:MIC).
      Major dosage adjustments for FQs are not necessary in hepatic insufficiency,
      accumulation of extracellular fluids, and burn patients. Appropriate dosage
      adjustments in renal function should be taken into consideration. FQ optimization
      in the critically ill is a multifactorial process that should be individualized
      to each patient and should take into account the MIC of the pathogen,
      pharmacokinetic/pharmacodynamic profile of the FQ, and the patient's
      pathophysiological state.

PMID- 18095223
TI  - Optimizing use of aminoglycosides in the critically ill.
AB  - In the era of increasing bacterial resistance and a lack of development of new
      antimicrobials for the treatment of gram-negative infections, aminoglycosides
      (AGs) are more commonly used in combination with other antimicrobials for the
      treatment of life-threatening infections in the intensive care unit (ICU). AGs
      display concentration-dependent killing activity; thus the rate and extent of
      bacterial killing increase with increasing peak (Cmax) drug concentrations.
      Optimizing AG dosing requires attainment of a pharmacodynamic target ratio
      (Cmax:minimal inhibitory concentration [MIC] > or = 10) upon first dose, which is
      associated with a more rapid rate of resolution of infection. Extended-interval
      AG dosing has been shown to attain this target in the general patient population
      while decreasing the risk of nephrotoxicity compared with multiple daily dosing.
      However, ICU patients have pharmacokinetic differences compared with patients who
      are less ill, including increased volume of distribution and variable clearance,
      which may make attainment of this target difficult. The need for extended
      interval aminoglycoside dosing with Cmax monitoring and MIC determination of the
      pathogen may be needed to optimally treat serious infections in the critically
      ill.

PMID- 18095224
TI  - Optimizing use of colistin and polymyxin B in the critically ill.
AB  - Polymyxin B and colistin are being used increasingly for the treatment of
      infections caused by gram-negative bacteria that are resistant to all other
      currently available antibiotics. Although the polymyxins have been available in
      the clinic for around 50 years, they have never been subjected to the drug
      development procedures required of modern pharmaceuticals. As a result, the
      available knowledge on the pharmacokinetics (PK), pharmacodynamics (PD), and
      toxicodynamics (TD) of the polymyxins is limited. Although significant advances
      have been made in the last 5 years or so, there are still large gaps in our
      understanding of the PK, PD, and TD, and of the PK/PD and PK/TD relationships.
      This information is required to generate recommendations on dosage regimens for
      various categories of critically ill patients. This paper reviews the growing
      understanding of the pharmacology of the polymyxins and factors that may impact
      on the optimization of the dose of these antibiotics in critically ill patients.

PMID- 18095225
TI  - Optimizing therapy for MRSA pneumonia.
AB  - With its remarkable armamentarium of resistance and virulence factors,
      Staphylococcus aureus has emerged as a dominant pathogen causing pneumonia of all
      classifications. Rates of methicillin resistance are increasing as clinicians
      struggle to find ways to prevent the acquisition of methicillin-resistant
      Staphylococcus aureus (MRSA) and to effectively treat MRSA pneumonia. Community
      associated MRSA has been identified as an important subset of MRSA with unique
      characteristics. Vancomycin remains a recommended first-line therapy for MRSA
      pneumonia, but resistance and therapeutic failures with vancomycin are being
      increasingly reported. Factors associated with vancomycin success or failure have
      been identified, including the genetics of the MRSA isolate, vancomycin lung
      penetration, minimum inhibitory concentration, and pharmacokinetic and
      pharmacodynamic variables. Retrospective analyses suggest that linezolid may
      provide improved outcomes compared with vancomycin for MRSA pneumonia, but
      validation in a prospective trial is currently lacking. Other treatment options
      are limited, but new prospects are being investigated. This paper reviews the
      epidemiology and pharmacotherapy of MRSA pneumonia.

PMID- 18095226
TI  - Optimizing therapy for methicillin-resistant Staphylococcus aureus bacteremia.
AB  - Methicillin-resistant Staphylococcus aureus bacteremia in patients in intensive
      care units is associated with significant morbidity and mortality. Prompt
      clinical attention is essential to ensure good outcomes, including identification
      and management of the source of infection and any associated complications.
      Foreign-body sources of infection should be removed or replaced in the majority
      of cases, and debridement of infectious foci should be undertaken. Particular
      attention should be given to evaluation for the presence of cardiac involvement
      because inadequately managed S. aureus endocarditis is life threatening.
      Selection of an appropriate antibiotic regimen is also an essential factor for
      optimal management.

PMID- 18095227
TI  - Optimizing therapy for vancomycin-resistant enterococci (VRE).
AB  - Enterococci are gram-positive, facultative bacteria with low intrinsic virulence
      but capable of causing a diverse variety of infections such as bacteremia with or
      without endocarditis, and intra-abdominal, wound, and genitourinary infection.
      During the past 2 decades the incidence of hospital-acquired enterococcal
      infection has significantly risen and is increasingly due to multidrug-resistant
      strains, primarily to the coacquisition of genetic determinants that encode for
      the stable expression of high-level beta-lactam, aminoglycoside, and glycopeptide
      resistance. Because enterococci constitute part of the normal colonizing flora,
      careful clinical interpretation of cultures that grow enterococci is paramount to
      avoid unnecessary and potentially deleterious antimicrobial therapy. Traditional
      antimicrobial treatment for ampicillin- and glycopeptide-susceptible enterococcal
      infection remains a penicillin-, ampicillin-, semisynthetic penicillin-based
      regimen, or vancomycin in a penicillin-intolerant individual. The need for a
      bactericidal combination with a cell-wall active agent combined with an
      aminoglycoside is most supported for native- or prosthetic valve endocarditis but
      is unproven for the majority of infections due to enterococci. The emergence of
      vancomycin-resistant enterococci prompted the clinical development of several
      novel and modified antimicrobial compounds approved for VRE infection
      (quinupristin-dalfopristin, linezolid) and several approved for non-VRE
      indications (daptomycin, tigecycline). There is a paucity of comparative clinical
      trial data with these new agents, although linezolid, based upon its efficacy and
      tolerability, appears to be the cornerstone of current treatment approaches.
      Despite a relatively short period of clinical use, enterococcal resistance has
      now been described for quinupristin-dalfopristin and linezolid and more recently
      even for daptomycin and tigecycline. Moreover, the optimal treatment of
      endocarditis due to VRE strains is unknown because, with the exception of
      daptomycin, current treatment options only yield bacteriostasis. Nonantimicrobial
      measures to treat VRE infection, such as foreign body removal and percutaneous or
      surgical drainage of close-spaced infection, reduce both the need for and the
      duration of anti-enterococcal treatment and the emergence of resistance to the
      newer antimicrobials.

PMID- 18095228
TI  - Optimizing therapy for infections caused by enterobacteriaceae producing extended
      spectrum beta-lactamases.
AB  - The spread of multidrug-resistant Enterobacteriaceae is complicating the
      treatment of nosocomial infections. In many parts of the world, resistance to
      third-generation cephalosporins exceeds 10% of total nosocomial isolates and 30%
      of isolates detected in the intensive care unit. This resistance is frequently
      due to the acquisition of plasmids containing genes encoding for extended
      spectrum beta-lactamases (ESBLs). Furthermore, these mobile elements often carry
      genes encoding resistance to other drugs such as aminoglycosides. A high risk of
      poor clinical outcome has been observed in patients infected with ESBL producers
      receiving third-generation cephalosporins, even if the organism appears
      susceptible to the antibiotic. For this reason, clinical microbiology
      laboratories are advised to incorporate specific ESBL detection methodology into
      routine clinical practice. This should prevent erroneous use of cephalosporins
      for these infections. Most ESBL producers remain susceptible to carbapenems, and
      these agents are considered the drugs of choice against ESBL-producing organisms.
      Unfortunately, there is now an increasing occurrence of carbapenem resistance in
      the Enterobacteriaceae. In this context, clinical response to new antibiotics
      (e.g., tigecycline) and old antibiotics (e.g., colistin) with good in vitro
      activity against ESBL producers needs to be evaluated.

PMID- 18095229
TI  - Optimizing antipseudomonal therapy in critical care.
AB  - Pseudomonas aeruginosa is a common and important pathogen in the critically ill.
      It combines environmental hardiness with genomic plasticity and is well adapted
      to the various niches available in the intensive care unit (ICU). Unresolved
      arguments over the value of dual versus monotherapy relate primarily to rapidity
      of killing and to the avoidance of therapeutic failure due to antibiotic
      resistance. Increasing resistance to conventional antibiotics means that we need
      to be aware of the factors that promote the success of this pathogen in the ICU,
      and of emerging alternative strategies. This review focuses on an understanding
      of the underlying issues and on the practical aspects of prescribing,
      particularly in the ICU.

PMID- 18095230
TI  - Optimizing therapy for Acinetobacter baumannii.
AB  - Acinetobacter baumannii is a highly resilient, gram-negative coccobacillus that
      thrives within the unique and complex ecological setting of an intensive care
      unit. This evolving pathogen has now surpassed human capacity to create new
      antimicrobials, and has led physicians into a concerning era for hospital
      acquired infections. This review presents the available evidence on the
      therapeutic strategies for A. baumannii infection, with a particular focus on
      clinical human data. The utility of existing and older antimicrobials such as
      sulbactam and the polymyxins are explored, as well as, the potential role of
      newer agents such as tigecycline. Other important adjunctive strategies such as
      pharmacodynamic target attainment and infection control implementation are
      briefly discussed. It is now clear that new antimicrobials with unique mechanisms
      of action are urgently required to combat the rising trends seen globally with
      drug-resistant A. baumannii.

PMID- 18095231
TI  - Optimizing therapy for Stenotrophomonas maltophilia.
AB  - Stenotrophomonas (Xanthomonas) maltophilia is a nonfermentative, gram-negative
      bacillus that is widely distributed in natural and human-made environments. In
      the nonhospital setting it is an uncommon pathogen, typically causing soft tissue
      infection of contaminated wounds. In the hospital setting, particularly among
      critical care and oncology patients, S. maltophilia may cause catheter-related
      bacteremia, pneumonia, soft tissue infection, meningitis, prosthetic valve
      endocarditis, and ocular infections. S. maltophilia is usually resistant to
      multiple antimicrobials, including expanded-spectrum penicillins, third
      generation cephalosporins, carbapenems, aminoglycosides, and quinolones.
      Trimethoprim-sulfamethoxazole is the antimicrobial agent of choice for this
      pathogen but is bacteriostatic. Further, resistance to this agent is increasing.
      Certain combinations of antibiotics are synergistic and may be appropriate for
      patients harboring resistant organisms or with life-threatening infections.

PMID- 18095232
TI  - Optimizing therapy for Candida infections.
AB  - The problem of invasive candidiasis among ICU patients is an increasing and
      evolving one. Despite advances in supportive care, increasing numbers of
      critically ill and vulnerable patients are susceptible to infection, and the
      clinical consequences for those who do develop invasive candidiasis remain poor.
      Evolving epidemiological trends, particularly a relative increase in the
      incidence of fluconazole-resistant Candida spp., have further complicated
      management. The recent availability of antifungal agents, such as voriconazole,
      the echinocandins, and lipid-associated amphotericin B preparations, with
      improved safety profiles, extended spectra, and proven clinical efficacies,
      offers new therapeutic options. However, optimizing therapy requires the
      consideration of numerous factors: the differing pharmacological properties of
      these agents, cost, the clinical status and progress of the patient, estimates of
      the likelihood of resistance, and microbiological data as they become available.
      Because early institution of antifungal therapy appears an important determinant
      of favorable outcome, accurate early microbiological and clinical markers of
      invasive candidiasis to guide early antifungal interventions are desperately
      needed and remain an area of active investigation.

PMID- 18095233
TI  - A comparison of the new indicator test for sudomotor function (Neuropad) with the
      vibration perception threshold and the clinical examination in the diagnosis of
      peripheral neuropathy in subjects with type 2 diabetes.
AB  - Peripheral neuropathy remains a major cause of morbidity and is a cardinal factor
      in the pathogenesis of diabetic foot ulceration. The aim of the present study was
      to compare the new indicator test for sudomotor function (Neuropad) with the
      vibration perception threshold (VPT) and the clinical examination in the
      diagnosis of peripheral neuropathy in subjects with type 2 diabetes. This study
      included 154 type 2 diabetic patients (76 men) with a mean age of 64.3+/-7.3
      years and a mean diabetes duration of 12.8+/-4.3 years. Neuropathy was diagnosed
      clinically using the Neuropathy Disability Score (NDS). The VPT was measured with
      a neurothesiometer, values > 25Volts being classified as abnormal. Sudomotor
      function was evaluated by the indicator test. Sensitivity of the indicator test
      for neuropathy was 97.8% and specificity was 67.2%. Sensitivity and specificity
      of VPT for neuropathy were 78.9% and 85.9% respectively. A significant
      correlation was shown between time to colour change of the indicator test and VPT
      (rs=0.889, p<0.001). CONCLUSIONS: Both the indicator test and the VPT have a high
      sensitivity for neuropathy. Sensitivity is higher with the indicator test, but
      specificity is higher with VPT. Time until complete colour change of the
      indicator test shows a positive correlation with VPT. Thus, the indicator test
      appears to be a useful additional diagnostic tool of neuropathy, particularly
      suitable for screening and self-examination, in type 2 diabetes. The correlation
      between time to colour change of the indicator test and VPT is interesting and
      merits investigation in a prospective study.

PMID- 18095235
TI  - A patient with a "good nose".
AB  - We report on a 33-year-old man who underwent an odyssey of doctors for
      investigation of dysphagia. Eventually, a nasopharyngeal mass was found by
      several otorhinolaryngologists who repeatedly recommended biopsy or excision,
      because a polyp or fibroma was assumed on nasal endoscopy and MR imaging.
      However, we finally diagnosed the nasopharyngeal mass to be an ectopic pituitary
      gland after thorough clinical (cleft lip and palate) and radiological re
      examination. Literally, the patient had a "good nose", since he refused
      manipulations on the nasopharyngeal tumour and assumably prevented inadvertent
      hypopituitarism. We conclude that biopsy or excision of nasopharyngeal masses
      should always be considered carefully, especially in patients with facial
      anomalies.

PMID- 18095234
TI  - Clinical benefit of a short term dietary oatmeal intervention in patients with
      type 2 diabetes and severe insulin resistance: a pilot study.
AB  - AIMS/HYPOTHESIS: To evaluate the potential effectiveness of 'carbohydrate days'
      as a dietary intervention to overcome insulin resistance in type 2 diabetes.
      MATERIALS AND METHODS: Patients (n=14) with uncontrolled type 2 diabetes and
      insulin resistance as defined by a dosage of more than 1 IU/day (*)kg BW were
      consecutively enrolled in this prospective study. Primary outcomes were daily
      insulin requirement and mean blood glucose levels which were evaluated before,
      after, and 4 weeks after the intervention. RESULTS: All patients had a metabolic
      syndrome, 75% had microvascular and 57.1% macrovascular complications. Hospital
      setting and diabetes adapted diet alone led to improved glycemic control with a
      mean blood glucose 158+/-47 mg/dl. Intervention with two days of oatmeal diet
      further decreased mean blood glucose to 118+/-37 mg/dl (p<0.05). This was
      associated with a significant reduction of insulin dosage by 42.5% (before: 145+/
      68.9 U/d, after 83+/-34.2 U/d, p<0.001) as well as a significant reduction (
      26.4%, p<0.01) of serum leptin levels. After the four weeks outpatient period,
      insulin dosage remained significantly decreased (83+/-20.2 U/kg (*)d, p<0.01).
      Glycemic control was comparable (mean blood glucose141+/-20.78 mg/dl) to glucose
      levels within the hospital setting. Adiponectin levels increased significantly by
      53.8% (p<0.05). CONCLUSIONS: In this uncontrolled pilot study, hospital admission
      and diabetes adapted diet followed by oatmeal intervention achieved a
      approximately 40% reduction of insulin dosage required to achieve controlled
      glucose levels. This effect was conserved after a 4 week outpatient phase with
      normal diet.

PMID- 18095236
TI  - A case of parathyroid carcinoma with severe hungry bone syndrome and review of
      literature.
AB  - We present a 45 year old female who was initially seen by Rheumatologist with
      long standing knee pain affecting her mobility. She was found to be severely
      hypercalcaemic and exhibited features suggestive of parathyroid carcinoma
      (palpable neck mass, extremely high parathyroid hormone, high alkaline
      phosphatase, concomitant presence of renal disease and skeletal involvement).
      Hence she was referred for parathyroidectomy. Postoperatively she developed
      profound hypocalcaemia with markedly raised serum alkaline phosphatase, requiring
      intensive intravenous calcium and oral vitamin D supplements, consistent with the
      development of hungry bone syndrome (HBS). HBS is a complication of parathyroid
      surgery where the correction of primary hyperparathyroidism is associated with
      rapid bone remineralisation, causing severe and prolonged hypocalcaemia. HBS is
      relatively rare but has to be considered in the differential diagnosis of
      postoperative hypocalcaemia particularly in severe cases. In the current report,
      we discuss pathogenesis, clinical course and management of HBS.

PMID- 18095237
TI  - Molecular cloning and expression of StAR protein in the canine corpus luteum
      during dioestrus.
AB  - Expression of the steroidogenic acute regulatory protein (StAR) in the canine
      corpus luteum (CL) was examined throughout the luteal phase covering the periods
      of CL formation, early and late regression. Following a homology cloning and
      characterization of a cDNA fragment of the canine StAR spanning the sequence
      coding for the open reading frame (ORF), which encodes a 286 amino acid protein
      being highly conserved (86-91%) between species, quantitative RT-PCR was
      performed with the respective primers. Expression of StAR was demonstrated on all
      days examined; mRNA-levels increased gradually in developing CL from day 5 until
      25; a steep, 4-fold downregulation was observed on day 35 with a further gradual
      decrease thereafter. Similar data were obtained by immunohistochemistry and the
      effect of time was highly significant (p<0.0001). These data suggest that the
      progesterone production during the canine CL-phase is controlled by the provision
      of substrate at the level of cholesterol transfer to the inner mitochondrial
      membrane, a step which involves the StAR-protein activity.

PMID- 18095238
TI  - Comparison of fixed-dose rosiglitazone/metformin combination therapy with
      sulphonylurea plus metformin in overweight individuals with Type 2 diabetes
      inadequately controlled on metformin alone.
AB  - AIM: This 52-week, randomized, double-blind, parallel-group study was designed to
      compare rosiglitazone/metformin fixed-dose combination therapy with combination
      sulphonylurea plus metformin therapy in overweight individuals with inadequately
      controlled type 2 diabetes mellitus. METHOD: Individuals with inadequate
      glycaemic control (HbA (1c)> or =7%) while on metformin monotherapy (> or =0.85
      g/day) entered a 4-week run-in period during which they received metformin 2
      g/day. At the end of the run-in, individuals with fasting plasma glucose > or
      =7.0 mmol/l were randomized to treatment with metformin (2 g/day) and either
      rosiglitazone (4 mg/day; RSG+MET [N=294]) or a sulphonylurea (glibenclamide 5
      mg/day or gliclazide 80 mg/day; SU+MET [N=302]). Medications were up-titrated to
      maximum tolerated doses (rosiglitazone 8 mg, glibenclamide 15 mg or gliclazide
      320 mg plus metformin 2 g/day) during the first 12 weeks of double-blind
      treatment. The primary efficacy end point was the change in HbA (1c) from
      baseline after 52 weeks of treatment. RESULTS: RSG+MET was non-inferior to SU+MET
      with respect to changes in HbA (1c) after one year of treatment (DeltaHbA (1c)= 
      0.78% and -0.86%, respectively; treatment difference =0.09%, 95% CI=-0.08, 0.25).
      The HbA (1c) reductions with RSG+MET, but not SU+MET, were accompanied by
      significant improvements in measures of beta-cell function including
      proinsulin:insulin ratio. The degree of beta-cell failure was significantly
      greater with SU+MET compared to RSG+MET as measured by the coefficient of failure
      (0.543 vs. 0.055 HbA (1c)%/year, respectively, p=0.0002). The proportion of
      individuals who experienced hypoglycaemic events was significantly (p<0.0001)
      lower with RSG+MET (6%) than with SU+MET (30%). Diastolic ambulatory blood
      pressure and cardiovascular biomarkers (high-sensitivity C-reactive protein and
      plasminogen activator inhibitor-1) were also reduced following one year of
      treatment with RSG+MET but not SU+MET. Both treatments were generally well
      tolerated. CONCLUSION: Fixed-dose combination therapy with
      rosiglitazone/metformin is non-inferior to sulphonylurea plus metformin
      combination therapy in reducing HbA (1c) over one year of treatment. Improvements
      in measures of beta-cell function suggest that the improvements in glycaemic
      control may be better maintained in long-term therapy with the
      rosiglitazone/metformin combination.

PMID- 18095239
TI  - An inhibition of the hypothalamic somatostatinergic tone is not the cause of the
      enhanced growth hormone response to growth hormone-releasing hormone in patients
      with liver cirrhosis.
AB  - Animal models of liver cirrhosis (LC) display a reduced hypothalamic
      somatostatinergic tone. To test whether a similar mechanism could explain the
      enhanced Growth Hormone (GH) secretory response to GH-Releasing Hormone (GHRH),
      which is seen in human LC, we studied the effect of the cholinesterase inhibitor
      pyridostigmine (PD), which is able to reduce the release of hypothalamic
      somatostatin (SS), on the GHRH-stimulated GH secretion. We considered that if PD
      were unable to increase GH secretion, this would constitute evidence of an
      already inhibited endogenous somatostatinergic tone. If proved, this in turn
      could explain the enhanced GH response to GHRH seen in LC. Ten LC patients and
      nine controls were given GHRH (100 microg, intravenously), or PD (120 mg, orally)
      plus GHRH. After GHRH alone, the GH peak was four times higher in LC than in
      controls (40.85+/-15.7 ng/ml in LC and 9.35+/-2.5 ng/ml in controls). In LC, PD
      administration markedly increased the GH response to GHRH (GH peak: 98.0+/-19.7
      ng/ml; +240% vs. GHRH alone). The ability of PD to increase the GH response in
      patients with LC suggests that in this condition the enhanced GH response to GHRH
      is not due to a completely inhibited endogenous somatostatinergic tone. SS
      appears instead to maintain its modulator role on GH secretion in human LC, in
      contrast with what observed in animal models.

PMID- 18095240
TI  - The relationship between body fat distribution and renal damage in Chinese with
      obesity.
AB  - OBJECTIVE: It has been recognized that in addition to being overweight, abnormal
      fat distribution may be associated with the etiology of metabolic syndrome. Asian
      people are more prone to develop visceral obesity than people in western
      countries. The present study was initiated to evaluate the relationship between
      visceral obesity and renal damage in Chinese obese people. METHODS: As measured
      by computed tomography, the areas of visceral fat were compared between 30
      patients with biopsy-proven obesity-related glomerulopathy (ORG) and 20 obese
      volunteer controls that were free of renal diseases. The two groups were matched
      for age and sex. RESULTS: It was found that the areas of visceral fat were
      markedly increased in patients with ORG, while body mass indexes were similar in
      the two groups. Patients with ORG also showed higher levels of total cholesterol
      and a higher degree of insulin resistance than the controls. Multiple logistic
      regression analysis revealed that visceral obesity was significantly associated
      with the prevalence of ORG (OR 1.136; 95%CI, 1.106-1.166; P=0.003).
      Interestingly, proteinuria level was related directly with waist circumference,
      visceral obesity and levels of total cholesterol, fasting glucose, insulin and
      HOMA-IR ( P<0.05). Moreover, only HOMA-IR was independently associated with
      proteinuria level in stepwise linear regression ( R=0.641; P=0.001). CONCLUSIONS:
      The present study illustrated the positive association between visceral obesity
      and ORG and between insulin resistance and proteinuria level in Chinese obese
      subjects.

PMID- 18095242
TI  - Wrist and hand ultrasound.
AB  - With adequate equipment, training, and expertise, ultrasound (US) should be
      regarded as the first-line imaging modality for the assessment of a wide range of
      pathological conditions affecting the soft tissues around the wrist and hand.
      With high-resolution transducers, US allows detection of foreign bodies and a
      reliable identification of a variety of traumatic lesions affecting tendons,
      retinacula and annular pulleys, ligaments, vessels, and nerves. In addition,
      inflammatory arthropathies, infectious disorders, overuse tendinopathies, and
      degenerative conditions can be diagnosed with this technique. In the wrist, US is
      able to identify the entrapment of the median, ulnar, and radial nerves. In
      patients with localized soft tissue swelling, US is able to assess the presence
      of a space-occupying lesion and to characterize its nature in many cases.

PMID- 18095243
TI  - Ultrasonography of the elbow.
AB  - Ultrasonography (US) of the elbow is an increasingly utilized modality for a
      variety of diagnoses. US is advantageous in many cases because of the ability to
      perform a dynamic examination while obtaining patient feedback. Furthermore, US
      is cost effective, widely available, and beautifully demonstrates superficial
      soft tissue structures. Finally, US is an excellent option for patients whose
      studies are degraded by motion artifact or those with claustrophobia concerns.
      The most common pathologies about the elbow are discussed in this article,
      including partial- and full-thickness tears of the biceps and triceps tendons,
      common extensor and flexor tendinosis, medial and lateral epicondylitis, radial
      and ulnar collateral ligament tears, ulnar nerve entrapment, cubital or olecranon
      bursitis, joint effusions, and intra-articular bodies. Relevant anatomy is
      detailed as it pertains to sonographic evaluation and appearance. In addition,
      specific imaging techniques and positions are described for optimum visualization
      of the various structures around the elbow because US is highly operator
      dependent.

PMID- 18095244
TI  - Ultrasound evaluation of the shoulder.
AB  - This article discusses ultrasound examination of the shoulder and highlights some
      of its utility. The focus is on normal shoulder anatomy and pathology involving
      the rotator cuff, biceps tendon, and other related miscellaneous conditions.

PMID- 18095245
TI  - Hip ultrasound.
AB  - Sonography has been widely utilized for several decades in the diagnosis and
      follow-up of developmental dysplasia of the hip due to its ability to visualize
      the nonossified femoral head and portions of the acetabulum in neonates, dynamic
      capabilities, accuracy, and lack of nonionizing radiation. Furthermore, hip
      sonography is also used throughout parts of the world to diagnose and guide
      intervention for both children and adults. The hip joint, tendons, and
      periarticular structures can be delineated with sonography in a variety of
      congenital, developmental, infectious, inflammatory, arthritic, traumatic, and
      neoplastic disorders. The following discussion focuses on the sonographic
      technique and imaging characteristics of congenital and developmental anomalies
      of the hip in children, as well as the sonographic evaluation of the hip joint
      and tendons.

PMID- 18095246
TI  - Ultrasound of the knee.
AB  - Ultrasound of the knee is best suited for the evaluation of tendons, fluid
      collections and effusion, synovitis, periarticular soft tissue masses, muscles,
      and the collateral ligaments. Advantages of sonographic evaluation include the
      lack of ionizing radiation, the noninvasive nature of the examination, focused
      evaluation correlated with the specific site of pain, multiplanar capability, and
      utility in patients for whom magnetic resonance imaging (MRI) is contraindicated.
      The ability to visualize the microanatomy of tendons, ligaments, nerves, and
      muscles is also an advantage over MRI. Moreover, ultrasound is generally readily
      accessible and of lower cost than MRI. Ultrasound is less suited for the
      evaluation of internal derangement. Certain structures that are exquisitely
      evaluated by MRI, including the menisci, cruciate ligaments, bone marrow, and
      articular cartilage, are suboptimally evaluated by sonography. This article
      reviews the structures and pathological processes for which ultrasound has been
      shown useful, emphasizing appropriate technique and normal anatomy, appearance of
      pathological processes, and advantages and limitations of sonographic evaluation.

PMID- 18095247
TI  - Ultrasound of ankle and foot: overuse and sports injuries.
AB  - Sports and overuse injuries of the ankle and foot are commonly encountered in
      clinical practice. Ultrasound (US) has been established as an excellent
      diagnostic modality for foot and ankle injuries, providing a rapid noninvasive,
      economical, and readily available tool that is well tolerated by the patient with
      acute or chronic pain. The opportunity for dynamic examination is another
      advantage of US in evaluating ankle and foot pathology, where maneuvers such as
      muscle contraction and stressing of the joint may be particularly helpful. In
      many cases, US can be used as a first-line and only imaging modality for
      diagnosis. This article focuses on ankle disorders related to sports or overuse
      that affect tendons, including tendinosis, tenosynovitis, paratendinitis,
      rupture, dislocation, and ligaments that are commonly torn. The sonographic
      features of certain common foot disorders related to physical activity and
      overuse are also discussed, including plantar fasciitis, Morton's neuroma, stress
      fractures, and plantar plate injury.

PMID- 18095248
TI  - Ultrasound of skeletal muscle injury.
AB  - The professional and recreational demands of modern society make the treatment of
      muscle injury an increasingly important clinical problem, particularly in the
      athletic population. In the elite athlete, significant financial and professional
      pressures may also exist that emphasize the need for accurate diagnosis and
      treatment. With new advances in ultrasound technology, images of exquisite detail
      allow diagnosis of muscle injury that matches the accuracy of magnetic resonance
      imaging (MRI). Furthermore, the benefits of real-time and Doppler imaging,
      ability to perform interventional procedures, and relative cost benefits compared
      with MRI place ultrasound at the forefront for investigation for these injuries
      in many circumstances. Muscle injury may be divided into acute and chronic
      pathology, with muscle strain injury the most common clinical problem presenting
      to sports physicians. This article reviews the spectrum of acute and chronic
      muscle injuries, with particular attention to clinical features and some common
      or important muscle strain injuries.

PMID- 18095249
TI  - Ultrasound evaluation of soft tissue masses and fluid collections.
AB  - Musculoskeletal ultrasound has utility as a first-line screening modality in the
      evaluation of soft tissue masses. The sonographic appearances of cysts or lipomas
      may be sufficient to obviate the need for further imaging. For other complex
      cystic or solid masses, ultrasound is an inexpensive, widely available imaging
      modality that can evaluate lesion vascularity, guide diagnostic and therapeutic
      aspiration or biopsy procedures, and be used for follow-up examinations to
      determine response to therapeutic interventions.

PMID- 18095250
TI  - Musculoskeletal interventional ultrasound.
AB  - Ultrasound is a nonionizing, low-cost, portable imaging technique for the
      evaluation of tendons, muscles, joints, soft tissue masses, and cysts, especially
      in patients unable to tolerate computed tomography or magnetic resonance imaging.
      These advantages make ultrasound an ideal modality for guiding musculoskeletal
      interventions. Its real-time capabilities allow continuous observation of needle
      placement into the targeted area and direct visualization of interventions such
      as injection of medication while avoiding other soft tissue structures or nearby
      neurovascular bundles. After a brief overview of the technical factors involved
      in performing ultrasound-guided musculoskeletal interventions, this article
      reviews commonly performed percutaneous procedures in the musculoskeletal system.

PMID- 18095251
TI  - Lower respiratory tract disease in children: constant pathogens - constant
      management?!
AB  - BACKGROUND: This study analyses the pathogens of acute lower respiratory tract
      infections (LRI) in children in a German community hospital over six years.
      Against this background the adoption of new diagnostic and therapeutic guidelines
      for the LRI management and of RSV-cases in particular is studied. METHODS: 1054
      children aged zero to 36 months hospitalized with LRI were prospectively included
      in the surveillance studies "Parainfluenzavirus (PIV) and Respiratory syncytial
      virus (RSV) infections in Germany [PRI.de] 1999-2001" and the "pediatric
      infectious diseases network on acute respiratory tract infections" [PID-ARI.net]
      for the time period of October 2002 until June 2005. The nasopharyngeal aspirates
      (NPA) of these children had been analysed for RSV, PIV 1,2,3 and influenzavirus
      (IV)-A, -B. In 2003/2004 the national guideline on how to diagnose and treat RSV
      disease (bronchiolitis) changed. Data on LRI cases severity and especially those
      regarding the clinical management of RSV-infections were compared to see
      differences following the release of the guideline. RESULTS: 84% of the children
      were between zero and 24 months old. 34% of the NPA specimens were positive for
      RSV, 7.7% for PIV 1,2,3 and 4.7% for IV-A, -B. Epidemiological findings did not
      differ substantially between the two studies. Clinical management of RSV-LRI,
      especially drug use, did not change except for the lower rate of x-ray
      examination (p<0.01). CONCLUSION: The spectrum of causing agents in LRI of
      children remained quite stable over of six years. Diagnostic and therapeutic
      concepts remain also stable in a situation where new guidelines were introduced,
      but not reinforced.

PMID- 18095252
TI  - [Chronological age of patients with Turner syndrome at diagnosis].
AB  - BACKGROUND: Phenotypically, Turner syndrome (TS) is characterized by great
      variability, with short stature being the most constant incidence. Growth hormone
      therapy can achieve a significant improvement in the final size of the patient,
      which, however, is highly dependent on early diagnosis of the disease. The
      objective of our study was to determine the age at which the affected girls among
      our patient collective were diagnosed with TS and which symptoms were indicative.
      PATIENTS: The time of diagnosis and the reason for karyotyping were
      retrospectively determined for 117 girls with TS, who had presented at the
      Hospital for Children and Adolescents of the University of Erlangen, Germany, in
      the period between 1980 and 2002. RESULTS: Seven children were prenatally
      diagnosed with TS by amniocentesis and 27 children were postnatally diagnosed
      with the disease. TS was diagnosed during infancy in 10 children (median 0.2
      years, range 0.1-0.9 yrs.), during early childhood in 4 children (median 1.7
      years, range 1.1-2.2 yrs.), and during preschool age in 11 girls (median 5 years,
      range 4-5.8 yrs.). In 58 girls, i.e. almost 50%, TS was diagnosed after the age
      of 6: n=27 between the age of 6 and 11 (median 8.9 years, range 6.1-10.8 yrs.)
      and n=31 after the age of 11 (median 13 years, range 11.1-17 yrs.). Lymphedema
      (26 cases), dysmorphic symptoms (14 cases), and heart failures (6 cases) were the
      reason for karyotyping performed at birth and during infancy. With increasing
      age, TS was diagnosed based on short stature (66 of 73 cases). CONCLUSIONS: The
      available data shows that the majority of the patients were diagnosed late and
      that short stature was the most important diagnostic symptom.

PMID- 18095253
TI  - Recent trends in the burden of alcohol intoxication on pediatric in-patient
      services in Germany.
AB  - AIMS: To elicit data on alcohol intoxications requiring in-patient treatment in
      children and adolescents in Germany between 2000 and 2002. DESIGN AND
      PARTICIPANTS: An ex-post analysis was performed to assess the number of children
      and adolescents (age 10-17 years) with acute alcohol intoxications requiring in
      patient hospital treatment (> or =24 hours). SETTING: 22 major children hospitals
      in Germany. FINDINGS: The number of acute alcohol intoxications requiring in
      patient treatment increased from 227 in 2000 to 313 in 2001 (+37.9%; p*<.01) and
      350 in 2002 (+10.6%; p*<.05). 10-12 year-old children comprised 2.2%, adolescents
      aged 13-14 years 28.6%, and adolescents aged 15-17 years 69.2% of the study
      population. The most significant increase was seen in adolescents aged 13-14
      years (2001: +35.9%, and 2002: +19.3%; p*<.05), and 15-17 years (2001: +59.1%,
      and 2002: +10.1%; p*<.05). The percentage of female patients increased from 34.1%
      in 2000 to 41.9% in 2001 and 49.8% in 2002 (p*<.05). Mean time spent in the
      hospital was 1.7 days (range: 1 day-->4 days). DISCUSSION AND CONCLUSIONS: This
      is one of the very few studies that provide epidemiological data on the specific
      issue of alcohol intoxications in children and adolescents that require in
      patient treatment. Apparently, gender differences seem to play a minor role in
      alcohol-related hospital admissions. Our data demonstrate that excessive alcohol
      consumption remains an issue of concern in this age cohort.

PMID- 18095254
TI  - [Purpura Schoenlein-Henoch: results of the Worlitz 2005 Consensus Conference
      focusing on diagnosis and therapy].
AB  - Henoch-Schoenlein Purpura (PSH) is the most frequent vasculitis in childhood.
      Skin, bowel and joints are characteristically involved. Although renal
      manifestations are common PSH-nephritis is infrequent but characterized by a poor
      prognosis. In autumn 2005 diagnosis and treatment were discussed at the 8th
      consensus meeting in Worlitz. These results are summarized.

PMID- 18095255
TI  - [Van-der-Woude Syndrome].
AB  - We report on two families with different expression of a Van-der-Woude-Syndrome
      (VWS) and with proven mutation of the IRF6- gene. The Van-der-Woude syndrome is a
      rare disease, typically consisting of congenital pits of the lower lip in
      combination with cleft lip or cleft palate or both. The Van-der-Woude syndrome is
      an autosomal dominant syndrome with variable expression. The penetrance is
      between 0,89 and 0,99. It is important to establish the correct diagnosis by
      careful investigation of patients with cleft lip or cleft palate and their
      parents. Genetic counselling is recommended in such cases.

PMID- 18095256
TI  - Cancer invasion and metastasis: changing views.
AB  - The formation of distant metastasis is the main cause of morbidity and mortality
      in patients with cancer. The aim of this article is to review recent advances in
      molecular and clinical aspects of metastasis. Traditionally, genes encoding
      extracellular matrix (ECM) processing proteases, adhesion proteins, and motility
      factors were thought to be amongst the main mediators of metastasis. Recently,
      however, genes activated during the early stages of tumourigenesis were
      implicated in the process. Conversely, genes thought to be primarily involved in
      metastasis such as urokinase plasminogen (uPA) and certain matrix
      metalloproteases (MMPs) are now known to also play a role in the early steps of
      tumour progression, perhaps by stimulating cell proliferation and/or promoting
      angiogenesis. Paradoxically, certain endogenous protease inhibitors such as PAI-1
      and TIMP-1 appear to promote cancer metastasis rather than inhibiting the
      process. These recent advances in our understanding should lead to the
      development of new molecular markers for predicting the likely formation of
      metastasis as well as the identification of new targets for anti-metastatic
      therapies.

PMID- 18095257
TI  - Bone marrow-derived myofibroblasts contribute functionally to scar formation
      after myocardial infarction.
AB  - Myofibroblasts play a major role in scar formation during wound healing after
      myocardial infarction (MI). Their origin has been thought to be interstitial
      cardiac fibroblasts. However, the bone marrow (BM) can be a source of
      myofibroblasts in a number of organs after injury. We have studied the temporal,
      quantitative and functional role of BM-derived (BMD) myofibroblasts in myocardial
      scar formation. MI was induced by permanent coronary artery ligation in mice
      reconstituted with EGFP or pro-Col1A2 transgenic BM. In the latter, luciferase
      and beta-galactosidase transgene expression mirrors that of the endogenous pro
      collagen 1A2 gene, which allows for functional assessment of the recruited cells.
      After MI, alpha-SMA-positive myofibroblasts and collagen I gradually increased in
      the infarct area until day 14 and remained constant afterwards. Numerous EGFP
      positive BMD cells were present during the first week post-MI, and gradually
      decreased afterwards until day 28. Peak numbers of BMD myofibroblasts, co
      expressing EGFP and alpha-SMA, were found on day 7 post-MI. An average of 21% of
      the BMD cells in the infarct area were myofibroblasts. These cells constituted up
      to 24% of all myofibroblasts present. By in vivo IVIS imaging, BMD myofibroblasts
      were found to be active for collagen I production and their presence was confined
      to the infarct area. These results show that BMD myofibroblasts participate
      actively in scar formation after MI.

PMID- 18095258
TI  - Lipid bilayers: an essential environment for the understanding of membrane
      proteins.
AB  - Membrane protein structure and function is critically dependent on the
      surrounding environment. Consequently, utilizing a membrane mimetic that
      adequately models the native membrane environment is essential. A range of
      membrane mimetics are available but none generates a better model of native
      aqueous, interfacial, and hydrocarbon core environments than synthetic lipid
      bilayers. Transmembrane alpha-helices are very stable in lipid bilayers because
      of the low water content and low dielectric environment within the bilayer
      hydrocarbon core that strengthens intrahelical hydrogen bonds and hinders
      structural rearrangements within the transmembrane helices. Recent evidence from
      solid-state NMR spectroscopy illustrates that transmembrane alpha-helices, both
      in peptides and full-length proteins, appear to be highly uniform based on the
      observation of resonance patterns in PISEMA spectra. Here, we quantitate for the
      first time through simulations what we mean by highly uniform structures. Indeed,
      helices in transmembrane peptides appear to have backbone torsion angles that are
      uniform within +/- 4 degrees . While individual helices can be structurally
      stable due to intrahelical hydrogen bonds, interhelical interactions within
      helical bundles can be weak and nonspecific, resulting in multiple packing
      arrangements. Some helical bundles have the capacity through their amino acid
      composition for hydrogen bonding and electrostatic interactions to stabilize the
      interhelical conformations and solid-state NMR data is shown here for both of
      these situations. Solid-state NMR spectroscopy is unique among the techniques
      capable of determining three-dimensional structures of proteins in that it
      provides the ability to characterize structurally the membrane proteins at very
      high resolution in liquid crystalline lipid bilayers.

PMID- 18095259
TI  - Studying porous materials with krypton-83 NMR spectroscopy.
AB  - This report is the first review of (83)Kr nuclear magnetic resonance as a new and
      promising technique for exploring the surfaces of solid materials. In contrast to
      the spin I = 1/2 nucleus of (129)Xe, (83)Kr has a nuclear spin of I = 9/2 and
      therefore possesses a nuclear electric quadrupole moment. Interactions of the
      quadrupole moment with the electronic environment are modulated by surface
      adsorption processes and therefore affect the (83)Kr relaxation rate and spectral
      lineshape. These effects are much more sensitive probes for surfaces than the
      (129)Xe chemical shielding and provide unique insights into macroporous materials
      in which the (129)Xe chemical shift is typically of little diagnostic value. The
      first part of this report reviews the effect of quadrupolar interactions on the
      (83)Kr linewidth in zeolites and also the (83)Kr chemical shift behavior that is
      distinct from that of its (129)Xe cousin in some of these materials. The second
      part reviews hyperpolarized (hp) (83)Kr NMR spectroscopy of macroporous materials
      in which the longitudinal relaxation is typically too slow to allow sufficient
      averaging of thermally polarized (83)Kr NMR signals. The quadrupolar-driven T(1)
      relaxation times of hp (83)Kr in these materials are sensitive to surface
      chemistry, surface-to-volume ratios, coadsorption of other species on surfaces,
      and surface temperature. Thus, (83)Kr T(1) relaxation can provide information
      about surfaces and chemical processes in macroscopic pores and can generate
      surface-sensitive contrast in hp (83)Kr MRI.

PMID- 18095260
TI  - A 3-factor model for the FACIT-Sp.
AB  - OBJECTIVE: The 12-item Functional Assessment of Chronic Illness Therapy-Spiritual
      Well-being Scale (FACIT-Sp) is a popular measure of the religious/spiritual (R/S)
      components of quality of life (QoL) in patients with cancer. The original factor
      analyses of the FACIT-Sp supported two factors: Meaning/Peace and Faith. Because
      Meaning suggests a cognitive aspect of R/S and Peace an affective component, we
      hypothesized a 3-factor solution: Meaning, Peace, and Faith. METHODS:
      Participants were 240 long-term female survivors of cancer who completed the
      FACIT-Sp, the SF-12, and the BSI 18. We used confirmatory factor analysis to
      compare the 2- and 3-factor models of the FACIT-Sp and subsequently assessed
      associations between the resulting solutions and QoL domains. RESULTS: Survivors
      averaged 44 years of age and 10 years post-diagnosis. A 3-factor solution of the
      FACIT-Sp significantly improved the fit of the model to the data over the
      original 2-factor structure (Delta chi(2)=72.36, df=2, p<0.001). Further
      adjustments to the 3-factor model resulted in a final solution with even better
      goodness-of-fit indices (chi(2)=59.11, df=1, p=0.13, CFI=1.00, SMRM=0.05).The
      original Meaning/Peace factor controlling for Faith was associated with mental
      (r=0.63, p<0.000) and physical (r=0.22, p<0.01) health on the SF-12, and the
      original Faith factor controlling for Meaning/Peace was negatively associated
      with mental health (r=-0.15, p<0.05). The 3-factor model was more informative.
      Specifically, using partial correlations, the Peace factor was only related to
      mental health (r=0.53, p<0.001); Meaning was related to both physical (r=0.18,
      p<0.01) and mental (r=0.17, p<0.01) health; and Faith was negatively associated
      with mental health (r=-0.17, p<0.05). CONCLUSION: The results of this study
      support a 3-factor solution of the FACIT-Sp. The new solution not only represents
      a psychometric improvement over the original, but also enables a more detailed
      examination of the contribution of different dimensions of R/S to QoL.

PMID- 18095262
TI  - The effect of group cohesion on rehabilitation outcome in cancer survivors.
AB  - OBJECTIVE: Group-based physical training interventions have been shown to be
      effective in increasing quality of life in cancer survivors. Until now, however,
      the impact of cohesion within the group on intervention outcome has not been
      investigated. METHODS: We examined self-reported individual group cohesion
      ratings collected in the first half of a 12-week rehabilitation programme for
      cancer survivors (N=132). Four dimensions of group cohesion were measured, i.e.
      the bond with the group as whole, the bond with other members, cooperation within
      the group and the instrumental value. Quality of life, physical functioning and
      fatigue were assessed before and after the intervention using the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      C30. Linear multiple multivariate regression analysis was conducted to explore
      the relationship between group cohesion and intervention outcome. RESULTS: The
      relationship between group cohesion and outcome was significantly modified by
      gender. Higher ratings of cooperation within the group predicted better post
      intervention quality of life and physical functioning and less fatigue in men,
      and better quality of life and physical functioning in women. Additionally, women
      who reported a stronger bond with other members showed a lower quality of life
      after the intervention. No relationship was found between the instrumental value
      and the outcome variables. CONCLUSION: Some dimensions of group cohesion seem to
      be associated with intervention outcome. The underlying mechanisms need to be
      unravelled.

PMID- 18095263
TI  - Structure elucidation and NMR spectral assignments of three new lignan glycosides
      from Akebia trifoliata.
AB  - Three new lignan glycosides (1-3) were isolated from the stems of Akebia
      trifoliata. Their structures were elucidated as
      (7R,8R,7'R,8'R)3,3',5,5'tetramethoxy-4,4'dihydroxy-7,9':7',9-diepoxylignan-4-O
      beta-D-glucopyranoside (1), (7S,8S,8'R)-4,4',9-trihydroxy-3,3',5,5'-tetramethoxy
      7,9'-epoxylignan-7'-one 9-O-beta-D-glucopyranoside (2), (7R,8R,8'S)-4,4',9
      trihydroxy3,3',5,5'-tetramethoxy-7,9'-epoxylignan-7'-one 9-O-beta-D
      glucopyranoside (3) by spectral analyses, primarily NMR, MS and CD. The NMR
      assignments for the compounds were carried out using 1H, 13C, DEPT, COSY, HSQC,
      HMBC and ROESY NMR experiments.

PMID- 18095264
TI  - 13C NMR studies of heterocyclic naphtho- and anthraquinones. Deshielding effect
      on the carbonyl carbon with methyl substitution.
AB  - 13C chemical shift assignment of several methyl substituted heterocyclic naphtho-
      and anthraquinones, including dihydronaphthofuranquinones, azaanthraquinones,
      benzopyrroloquinolinediones and benzothiophenoquinolinediones, are described. A
      deshielding effect due to a methyl group was observed over the neighbouring
      carbonyl carbon, in every case studied. 13C assignments were based on 2D
      experiments.

PMID- 18095265
TI  - Torsion sensitivity in NMR of aligned molecules: study on various substituted
      biphenyls.
AB  - To estimate the torsion sensitivity of dipolar coupling, biphenylic molecules
      were chosen as probes due to their relatively simple structure and the
      surprisingly high ambiguity of the only flexible parameter-the interring torsion
      angle. Solution structures of 4,4'-dibromobiphenyl and 4,4'-diiodobiphenyl are
      reported for the first time in two liquid crystals I52 and ZLI 1695. The
      comparison of NMR structures of various para-substituted biphenyls (BPs),
      calculated by the additive potential maximum entropy (APME) approach, shows that
      the small spread of torsion angle values in case of different solvents and para
      substituents is in good agreement with theoretical expectations from hybrid
      density functional theory (DFT) methods. Furthermore, the real structural changes
      of interring torsion and the prevalence of solvent effects over para
      halosubstitution can be correctly revealed from these small fluctuations.

PMID- 18095266
TI  - Tumor size: a non-neglectable independent prognostic factor for gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: The role of tumor size should not be neglected in the
      management of gastric cancer and its prognostic value needs precise reevaluation.
      METHODS: The survival data of 513 patients who underwent radical resection
      between 2000 and 2005 were collected retrospectively. Tumor size, measured as the
      maximum diameter of tumor, was categorized into four subgroups (< or =2, < or =3,
      < or =5, >5 cm) using the method of minimizing the estimated average expected
      distance (AED) objective function. The prognostic value of tumor size and the
      correlation between tumor size and other clinicopathologic factors were
      investigated. RESULTS: In multivariate analysis, status of lymph nodes (P <
      0.001), depth of invasion (P < 0.001), type of resection (P = 0.004), age (P =
      0.008), tumor size (P = 0.014), and perioperative blood transfusion (P = 0.034)
      were confirmed as independent prognostic predictors for patients with gastric
      cancer. Log linear model suggested that the status of lymph nodes and the depth
      of invasion associated with the tumor size significantly. CONCLUSIONS: The tumor
      size is a non-neglectable independent prognostic factor for patients with gastric
      cancer and more attention should be paid to its role in the management of gastric
      cancer.

PMID- 18095267
TI  - The significances of lymph node micrometastasis and its correlation with E
      cadherin expression in pT1-T3N0 gastric adenocarcinoma.
AB  - BACKGROUND: Recently, micrometastasis (MM) in the lymph node in gastric cancer
      has been detected by cytokeratin immunostaining. However, clinical significance
      of MM and its relationship with reduced expression of E-cadherin in primary
      lesion have not been well studied. METHODS: The 4,990 lymph nodes from 184
      pT1~T3N0 patients from 1995 to 2000 at Korea University Hospital were
      immunostained with the anticytokeratin AE1/3 antibody for detection of
      micometastasis. The primary lesions were also immunostained for E-cadherin
      expression. RESULTS: MM in the lymph node of gastric cancer was found in 131
      (2.6%) of total dissected nodes, and 31 of 184 patients (16.8%) were shown to
      have MM. The MM was significantly correlated with the depth of invasion, tumor
      size, operation method, Lauren classification, lymphovascular invasion and loss
      of E-cadherin expression in primary tumor. On multivariate analysis, the
      independent risk factors for MM were the depth of invasion and loss of E-cadherin
      expression. The patients with MM had significantly lower 5-year overall and
      disease free survival rate than those without MM. CONCLUSION: Lymph node MM in
      histologically node-negative gastric cancer was significantly correlated with
      poor 5-year survival rate. The determination of E-cadherin expression in primary
      gastric tumor may be useful in prediction of the MM.

PMID- 18095268
TI  - "Spontaneous," delayed colon and rectal anastomotic complications associated with
      bevacizumab therapy.
AB  - Bevacizumab, a humanized monoclonal antibody used to treat recurrent and
      metastatic colorectal cancer, targets the vascular endothelial growth factor
      (VEGF) molecule. It is hypothesized that bevacizumab works by both depriving
      tumors of the neovascularity they require to grow, and by improving local
      delivery of chemotherapy through alterations of tumor vasculature permeability
      and Starling forces. Complications of bevacizumab treatment include bowel
      ischemia and perforation, but to date, these complications have only rarely been
      described as occurring at the site of presumably healed anastomoses following
      surgery. We report two cases of delayed, "spontaneous" low anterior colorectal
      anastomotic dehiscence and one right colon anastomotic colocutaneous fistula
      associated with bevacizumab therapy. After seeing three patients with
      complications arising from apparently healed low anterior colorectal or right
      colon anastomoses following initiation of bevacizumab therapy for treatment of
      metastatic colorectal cancer, we reviewed the experience of The Cancer Institute
      of New Jersey (CINJ) with use of bevacizumab in approximately 50 patients between
      April 2004 and December 2006. The three index cases had been treated surgically
      at CINJ but received chemotherapy elsewhere. None of the 50 patients receiving
      bevacizumab at CINJ who had previous colon or rectal anastomoses were identified
      as having this complication. The medical records of the three index cases were
      reviewed and analyzed. Additionally, a Medline search was performed to identify
      other reports documenting similar cases. Two reports of related cases were found
      in the literature. In two of our index cases who underwent low anterior
      anastomoses, the patients had received preoperative pelvic irradiation before
      their initial low anterior resection. In one of the two cases, the initial
      resection was complicated by an anastomotic leak requiring proximal diversion and
      then subsequent stoma takedown. In both cases, the dehiscence occurred more than
      1 year after anastomosis, and became evident 1-10 months following initiation of
      bevacizumab treatment. In the third index case, a colocutaneous fistula arising
      from the anastomotic site presented 5 months following right colon resection and
      3 months after starting adjuvant systemic therapy with FOLFOX (5-fluorouracil (5
      FU), leucovorin, and oxaliplatin) and bevacizumab. Delayed colorectal anastomotic
      complications may occur in association with bevacizumab therapy. Contributing
      factors may include anastomotic leak at the time of the original operation and
      history of anastomotic irradiation. Clinicians treating patients who receive
      bevacizumab following colectomy for colorectal cancer should be aware of this
      possible life-threatening complication. These findings may also be relevant to
      the design of trials of the use of bevacizumab for the postoperative adjuvant
      treatment of patients with colorectal cancer.

PMID- 18095269
TI  - Laparoscopic pancreas- and spleen-preserving D2 lymph node dissection in advanced
      (cT2) upper-third gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Although the laparoscopic assisted total gastrectomy
      (LATG) has been performed in upper gastric cancer, dissection of lymph nodes No.
      10 and 11d without resection of the distal pancreas and the spleen has been hard
      to accomplish, because of the possibilities of injury to splenic vessels and
      parenchyma of the spleen or pancreas. Herein, we present successful results in
      laparoscopic pancreas- and spleen-preserving D2 lymph node dissection in advanced
      upper gastric cancer. METHODS: Between March 2004 and May 2007, 18 clinical T2
      patients who underwent LATG with D2 lymph node dissection for upper gastric
      cancer were enrolled. RESULTS: We used the technique of encircling and pulling
      the splenic artery with umbilical tape and that helped us complete dissection of
      lymph nodes No. 10 and 11d without distal pancreatectomy or splenectomy. The mean
      operative time was 370 min without any perioperative complications or conversion
      to an open procedure. CONCLUSIONS: Laparoscopic extended lymph node dissection
      without pancreatectomy or splenectomy can be adapted to the patients with
      clinical T2 upper gastric cancer. The techniques like taping of the splenic
      artery can be a useful tip for surgeons who wish to perform laparoscopic complete
      D2 lymph node dissection in advanced upper gastric cancer.

PMID- 18095270
TI  - Prostate-specific genes and their regulation by dihydrotestosterone.
AB  - BACKGROUND: Prostate is a well-known androgen-dependent tissue. METHODS: By
      sequencing 4,294,186 serial analysis of gene expression (SAGE) tags, we have
      investigated the transcriptomes of normal mouse prostate, liver, testis, lung,
      brain, femur, skin, adipose tissue, skeletal muscle, vagina, ovary, mammary
      gland, and uterus in order to identify the most abundant and tissue-specific
      transcripts in the prostate, as well as to target the androgen responsive
      transcripts specifically regulated in the prostate. Small interference RNA
      (siRNA) in LNCaP cells was applied to validate the roles of prostate
      specific/enriched ARGs in the growth of human prostate cancer cells. RESULTS: The
      most abundant transcripts were involved in prostatic secretion, energy metabolism
      and immunity. Previously well-known prostate-specific transcripts, including many
      transcripts involved in prostatic secretion, polyamine biosynthesis and
      transport, and immunity were specific/enriched in the prostate. Only 22
      transcripts among 114 androgen-regulated genes (ARGs) in the mouse prostate were
      modulated by dihydrotestosterone (DHT) in two or more tissues. The siRNA results
      showed that inhibition of HSPA5 and MAT2A gene expression repressed growth of
      human cancer LNCaP cells. CONCLUSIONS: The current study globally assessed the
      transcriptome of the prostate and revealed the most abundant and tissue-specific
      transcripts which are responsible for the unique functions of this organ. These
      prostate-specific ARGs might be used as targets to develop safe and effective
      gene-based therapy for the prevention and treatment of prostate cancer.

PMID- 18095271
TI  - The clinical significance of loss of control over eating in overweight
      adolescents.
AB  - OBJECTIVE: Given limited data on the diagnostic validity of binge eating disorder
      (BED) in adolescents, this study sought to characterize overweight adolescents
      according to types of overeating episodes. METHOD: Ninety-six adolescents (ages
      13-17 years) with recurrent binge eating (BE), loss of control with or without
      overeating (subclinical BE; SUB), overeating without loss of control (OE), and no
      overeating or loss of control episodes (CONTROL) were compared on weight/shape
      concerns and depressive symptoms using ANCOVA and post-hoc least squares
      difference tests. RESULTS: BE and SUB adolescents had higher weight/shape concern
      scores than OEs and CONTROLs (ps < .01). BE and SUB adolescents had higher
      depression scores than CONTROL adolescents (ps < .05). BE adolescents had greater
      depression scores than OE (p < .01) but not SUB adolescents. CONCLUSION: Loss of
      control over eating signals increased impairment independent of overeating in
      adolescents. Results support refining BED criteria for youth to reflect this
      distinction.

PMID- 18095273
TI  - Estimating survival in newly diagnosed cancer patients: use of computer
      simulations to evaluate performances of different approaches in a wide range of
      scenarios.
AB  - Many empirical studies have proven the usefulness of period analysis in providing
      more up-to-date estimates of cancer patient survival than cohort-based methods.
      The aim of this paper is to provide a non-empirical evaluation of several
      survival approaches over a comprehensive range of scenarios using computer
      simulations. The simulation model included the following input parameters: number
      of annual patients, length of survival calculation, number of years of diagnosis,
      prognosis of cancer, follow-up period, and two additional parameters for modeling
      assumption on incidence and survival trends. The current study also introduced
      alternative cohort- and period-based approaches in addition to more traditional
      methods. Simulations showed that the choice of an appropriate survival approach
      is strongly dependent on the given scenario: period analysis was effective only
      for a limited number of circumstances, while alternative approaches appeared to
      be suitable for more realistic situations, when the follow-up period is different
      from the incidence period. The results of simulations could be useful for a quick
      identification of the most appropriate approach when estimating up-to-date cancer
      survival rates.

PMID- 18095272
TI  - Fyn is a novel target of (-)-epigallocatechin gallate in the inhibition of JB6
      Cl41 cell transformation.
AB  - The cancer preventive action of (-)-epigallocatechin gallate (EGCG), found in
      green tea, is strongly supported by epidemiology and laboratory research data.
      However, the mechanism by which EGCG inhibits carcinogenesis and cell
      transformation is not clear. In this study, we report that EGCG suppressed
      epidermal growth factor (EGF)-induced cell transformation in JB6 cells. We also
      found that EGCG inhibited EGF-induced Fyn kinase activity and phosphorylation in
      vitro and in vivo. Fyn was implicated in the process because EGF-induced JB6 cell
      transformation was inhibited by small interfering RNA (siRNA)-Fyn-JB6 cells. With
      an in vitro protein-binding assay, we found that EGCG directly bound with the GST
      Fyn-SH2 domain but not the GST-Fyn-SH3 domain. The K(d) value for EGCG binding to
      the Fyn SH2 domain was 0.367 +/- 0.122 microM and B(max) was 1.35 +/- 0.128
      nmol/mg. Compared with control JB6 Cl41 cells, EGF-induced phosphorylation of p38
      MAP kinase (p38 MAPK) (Thr180/Tyr182), ATF-2 (Thr71) and signal transducer and
      activator of transcription 1 (STAT1) (Thr727) was decreased in siRNA-Fyn-JB6
      cells. EGCG could inhibit the phosphorylation of p38 MAPK, ATF-2, and STAT1. The
      DNA binding ability of AP-1, STAT1, and ATF-2 was also decreased in siRNA-Fyn-JB6
      cells. Overall, these results demonstrated that EGCG interacted with Fyn and
      inhibited Fyn kinase activity and thereby regulated EGF-induced cell
      transformation. Inhibition of Fyn kinase activity is a novel and important
      mechanism that may be involved in EGCG-induced inhibition of cell transformation.

PMID- 18095274
TI  - Rh III- and Ir III-catalyzed asymmetric transfer hydrogenation of ketones in
      water.
AB  - Asymmetric transfer hydrogenation (ATH) of ketones by formate in neat water is
      shown to be viable with Rh-TsDPEN and Ir-TsDPEN catalysts, derived in situ from
      [Cp*MCl2]2 (M=Rh, Ir) and TsDPEN. A variety of ketones were reduced, including
      nonfunctionalized aryl ketones, heteroaryl ketones, ketoesters, and unsaturated
      ketones. In comparison with Ir-TsDPEN and the related Ru II catalyst, the Rh III
      catalyst is most efficient in water, affording enantioselectivities of up to 99 %
      ee at substrate/catalyst (S/C) ratios of 100-1000 even without working under an
      inert atmosphere. The aqueous phase reduction is shown to be highly pH-dependent;
      the optimum pH windows for TOF greater than 50 mol mol(-1) h(-1) for Rh- and Ir
      TsDPEN are 5.5-10.0 and 6.5-8.5, respectively. Outside the pH window, the
      reduction becomes slow or stagnant depending on the pH. However, the
      enantioselectivities erode only under acidic conditions. At a higher S/C ratio,
      the aqueous ATH by Rh-TsDPEN is shown to be product- as well as byproduct
      inhibited; the product inhibition appears to stem at least partly from the
      reaction being reversible. The aqueous phase reduction is simple, efficient and
      environmentally benign, thus presenting a viable alternative for asymmetric
      reduction.

PMID- 18095275
TI  - Bayesian modeling of multivariate average bioequivalence.
AB  - Bioequivalence trials are usually conducted to compare two or more formulations
      of a drug. Simultaneous assessment of bioequivalence on multiple endpoints is
      called multivariate bioequivalence. Despite the fact that some tests for
      multivariate bioequivalence are suggested, current practice usually involves
      univariate bioequivalence assessments ignoring the correlations between the
      endpoints such as AUC and C(max). In this paper we develop a semiparametric
      Bayesian test for bioequivalence under multiple endpoints. Specifically, we show
      how the correlation between the endpoints can be incorporated in the analysis and
      how this correlation affects the inference. Resulting estimates and posterior
      probabilities 'borrow strength' from one another where the amount and the
      direction of the strength borrowed are determined by the prior correlations. The
      method developed is illustrated using a real data set.

PMID- 18095276
TI  - Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers.
AB  - Experimental panic induction with cholecystokinin tetrapeptide (CCK-4) is
      considered as a suitable model to investigate the pathophysiology of panic
      attacks. While only a few studies investigated the brain activation patterns
      following CCK-4, no data are available on the putative involvement of the
      amygdala in the CCK-4 elicited anxiety response. We studied the functional
      correlates of CCK-4-induced anxiety in healthy volunteers by means of functional
      magnetic resonance imaging (fMRI) and region of interest (ROI) analysis of the
      amygdala. Sixteen healthy volunteers underwent challenge with CCK-4 compared with
      placebo in a single-blind design. Functional brain activation patterns were
      determined for the CCK-4-challenge, the placebo response and anticipatory anxiety
      (AA). CCK-4-induced anxiety was accompanied by a strong and robust activation
      (random effects analysis, P < 0.00001, uncorrected for multiple testing) in the
      ventral anterior cingulate cortex (ACC), middle and superior frontal gyrus,
      precuneus, middle and superior temporal gyrus, occipital lobe, sublobar areas,
      cerebellum, and brainstem. In contrast, random effects group analysis for placebo
      and AA using the same level of significance generated no significant results.
      Using a more liberal level of significance, activations could be observed in some
      brain regions such as the dorsal part of the ACC during AA (random effects
      analysis, P < 0.005). Overall functional responses did not differ between
      panickers and nonpanickers. Only 5 of 11 subjects showed strong amygdala
      activation. However, ROI analysis pointed towards higher scores in fear items in
      these subjects. In conclusion, while overall brain activation patterns are not
      related to the subjective anxiety response to CCK-4, amygdala activation may be
      involved in the subjective perception of CCK-4-induced fear.

PMID- 18095277
TI  - Task-relevance and temporal synchrony between tactile and visual stimuli
      modulates cortical activity and motor performance during sensory-guided movement.
AB  - Sensory-guided movements require the analysis and integration of task-relevant
      sensory inputs from multiple modalities. This article sought to: (1) assess
      effects of intermodal temporal synchrony upon modulation of primary somatosensory
      cortex (S1) during continuous sensorimotor transformations, (2) identify cortical
      areas sensitive to temporal synchrony, and (3) provide further insight into the
      reduction of S1 activity during continuous vibrotactile tracking previously
      observed by our group (Meehan and Staines 2007: Brain Res 1138:148-158).
      Functional MRI was acquired while participants received simultaneous bimodal
      (visuospatial/vibrotactile) stimulation and continuously tracked random changes
      in one modality, by applying graded force to a force-sensing resistor. Effects of
      intermodal synchrony were investigated, unbeknownst to the participants, by
      varying temporal synchrony so that sensorimotor transformations dictated by the
      distracter modality either conflicted (low synchrony) or supplemented (high
      synchrony) those of the target modality. Temporal synchrony differentially
      influenced tracking performance dependent upon tracking modality.
      Physiologically, synchrony did not influence S1 activation; however, the insula
      and superior temporal gyrus were influenced regardless of tracking modality. The
      left temporal-parietal junction demonstrated increased activation during high
      synchrony specific to vibrotactile tracking. The superior parietal lobe and
      superior temporal gyrus demonstrated increased activation during low synchrony
      specific to visuospatial tracking. As previously reported, vibrotactile tracking
      resulted in decreased S1 activation relative to when it was task-irrelevant. We
      conclude that while temporal synchrony is represented at higher levels than S1,
      interactions between inter- and intramodal mechanisms determines sensory
      processing at the level of S1.

PMID- 18095278
TI  - Late evening brain activation patterns and their relation to the internal
      biological time, melatonin, and homeostatic sleep debt.
AB  - Sleep propensity increases sharply at night. Some evidence implicates the pineal
      hormone melatonin in this process. Using functional magnetic resonance imaging,
      brain activation during a visual search task was examined at 22:00 h (when
      endogenous melatonin levels normally increase). The relationships between brain
      activation, endogenous melatonin (measured in saliva), and self-reported fatigue
      were assessed. Finally, the effects of exogenous melatonin administered at 22:00
      h were studied in a double blind, placebo-controlled crossover manner. We show
      that brain activation patterns as well as the response to exogenous melatonin
      significantly differ at night from those seen in afternoon hours. Thus,
      activation in the rostro-medial and lateral aspects of the occipital cortex and
      the thalamus diminished at 22:00 h. Activation in the right parietal cortex
      increased at night and correlated with individual fatigue levels, whereas
      exogenous melatonin given at 22:00 h reduced activation in this area. The right
      dorsolateral prefrontal cortex, an area considered to reflect homeostatic sleep
      debt, demonstrated increased activation at 22:00 h. Surprisingly, this increase
      correlated with endogenous melatonin. These results demonstrate and partially
      differentiate circadian effects (whether mediated by melatonin or not) and
      homeostatic sleep debt modulation of human brain activity associated with
      everyday fatigue at night.

PMID- 18095279
TI  - Re-entrant projections modulate visual cortex in affective perception: evidence
      from Granger causality analysis.
AB  - Re-entrant modulation of visual cortex has been suggested as a critical process
      for enhancing perception of emotionally arousing visual stimuli. This study
      explores how the time information inherent in large-scale electrocortical
      measures can be used to examine the functional relationships among the structures
      involved in emotional perception. Granger causality analysis was conducted on
      steady-state visual evoked potentials elicited by emotionally arousing pictures
      flickering at a rate of 10 Hz. This procedure allows one to examine the direction
      of neural connections. Participants viewed pictures that varied in emotional
      content, depicting people in neutral contexts, erotica, or interpersonal attack
      scenes. Results demonstrated increased coupling between visual and cortical areas
      when viewing emotionally arousing content. Specifically, intraparietal to
      inferotemporal and precuneus to calcarine connections were stronger for
      emotionally arousing picture content. Thus, we provide evidence for re-entrant
      signal flow during emotional perception, which originates from higher tiers and
      enters lower tiers of visual cortex.

PMID- 18095280
TI  - Differential patterns of cortical activation as a function of fluid reasoning
      complexity.
AB  - Fluid intelligence (gf) refers to abstract reasoning and problem solving
      abilities. It is considered a human higher cognitive factor central to general
      intelligence (g). The regions of the cortex supporting gf have been revealed by
      recent bioimaging studies and valuable hypothesis on the neural correlates of
      individual differences have been proposed. However, little is known about the
      interaction between individual variability in gf and variation in cortical
      activity following task complexity increase. To further investigate this, two
      samples of participants (high-IQ, N = 8; low-IQ, N = 10) with significant
      differences in gf underwent two reasoning (moderate and complex) tasks and a
      control task adapted from the Raven progressive matrices. Functional magnetic
      resonance was used and the recorded signal analyzed between and within the
      groups. The present study revealed two opposite patterns of neural activity
      variation which were probably a reflection of the overall differences in
      cognitive resource modulation: when complexity increased, high-IQ subjects showed
      a signal enhancement in some frontal and parietal regions, whereas low-IQ
      subjects revealed a decreased activity in the same areas. Moreover, a direct
      comparison between the groups' activation patterns revealed a greater neural
      activity in the low-IQ sample when conducting moderate task, with a strong
      involvement of medial and lateral frontal regions thus suggesting that the
      recruitment of executive functioning might be different between the groups. This
      study provides evidence for neural differences in facing reasoning complexity
      among subjects with different gf level that are mediated by specific patterns of
      activation of the underlying fronto-parietal network.

PMID- 18095281
TI  - Functional connectivity patterns during motor behaviour: the impact of past on
      present activity.
AB  - Everyday behaviour often depends on the performance of multiple movements
      executed in a particular order. Here, the impact of task history on the neural
      activation patterns of motor behaviour is examined by evaluating unimanual and
      bimanual actions that are produced in a serial arrangement, such that switching
      between tasks is required. Cortical dynamics was assessed by means of EEG
      coherence in the beta frequency band (13-30 Hz). Results showed that although
      behavioural performance was not affected, switching trials induced increased
      coherence as compared to control (repeat) trials. This reorganization was
      dependent on task history and was more pronounced for unimanual than for bimanual
      tasks. Overall, the data illustrate that neural processing of motor behaviour
      within a serial arrangement integrates past and present activity, and accordingly
      impacts on neural efficiency.

PMID- 18095282
TI  - Improved application of independent component analysis to functional magnetic
      resonance imaging study via linear projection techniques.
AB  - Spatial Independent component analysis (sICA) has been widely used to analyze
      functional magnetic resonance imaging (fMRI) data. The well accepted implicit
      assumption is the spatially statistical independency of intrinsic sources
      identified by sICA, making the sICA applications difficult for data in which
      there exist interdependent sources and confounding factors. This interdependency
      can arise, for instance, from fMRI studies investigating two tasks in a single
      session. In this study, we introduced a linear projection approach and considered
      its utilization as a tool to separate task-related components from two-task fMRI
      data. The robustness and feasibility of the method are substantiated through
      simulation on computer data and fMRI real rest data. Both simulated and real two
      task fMRI experiments demonstrated that sICA in combination with the projection
      method succeeded in separating spatially dependent components and had better
      detection power than pure model-based method when estimating activation induced
      by each task as well as both tasks.

PMID- 18095283
TI  - Neural substrates of phonological and lexicosemantic representations in
      Alzheimer's disease.
AB  - The language profile of patients suffering from Alzheimer's disease (AD) is
      characterized not only by lexicosemantic impairments but also by phonological
      deficits, as shown by an increasing number of neuropsychological studies. This
      study explored the functional neural correlates underlying phonological and
      lexicosemantic processing in AD. Using H(215)O PET functional brain imaging, a
      group of mild to moderate AD patients and a group of age-matched controls were
      asked to repeat four types of verbal stimuli: words, wordlike nonwords (WL+), non
      wordlike nonwords (WL-) and simple vowels. The comparison between the different
      conditions allowed us to determine brain activation preferentially associated
      with lexicosemantic or phonological levels of language representations. When
      repeating words, AD patients showed decreased activity in the left temporo
      parietal and inferior frontal regions relative to controls, consistent with
      distorted lexicosemantic representations. Brain activity was abnormally increased
      in the right superior temporal area during word repetition, a region more
      commonly associated with perceptual-phonological processing. During repetition of
      WL+ and WL- nonwords, AD patients showed decreased activity in the middle part of
      the superior temporal gyrus, presumably associated with sublexical phonological
      information; at the same time, AD patients showed larger activation than controls
      in the inferior temporal gyrus, typically associated with lexicosemantic levels
      of representation. Overall, the results suggest that AD patients use altered
      pathways to process phonological and lexicosemantic information, possibly related
      to a progressive loss of specialization of phonological and lexicosemantic neural
      networks.

PMID- 18095284
TI  - When do infants differentiate profile face from frontal face? A near-infrared
      spectroscopic study.
AB  - The objective of the present study was to determine whether a developmental
      difference occurs in brain activity when infants look at frontal and profile
      views using near-infrared spectroscopy (NIRS), which is an optical imaging
      technique used to measure changes in the concentrations of oxyhemoglobin (oxy
      Hb), deoxyhemoglobin (deoxy-Hb), and total hemoglobin (total-Hb). For this
      objective, we compared NIRS results in two age groups, 5- and 8-month-old
      infants, while they were looking at frontal views, profile views, and objects. We
      found that the concentration of oxy-Hb and total-Hb in the 5-month-old group
      increased for only frontal views in the right temporal regions. In contrast, the
      concentration of oxy-Hb and total-Hb in the 8-month-old group increased for both
      frontal and profile views in the right temporal regions. Therefore, the present
      study indicated that the right hemisphere was dominant for the perception of
      profile views as well as frontal views. In addition, the most important and
      interesting finding was that the infants' brain activity of the face area would
      become view-invariant at the age of 8 months but not at 5 months. The
      developmental period for view-invariant face recognition has been discussed in
      previous psychological studies, but this is the first objective study to confirm
      that the period is between 5- and 8-months by measuring the blood flow in the
      brain using NIRS.

PMID- 18095285
TI  - Effective connectivity of the left BA 44, BA 45, and inferior temporal gyrus
      during lexical and phonological decisions identified with DCM.
AB  - Distinct regions in the left inferior frontal gyrus (IFG) preferentially support
      the processing of different word-types (e.g., real words, pseudowords) and tasks
      (e.g., lexical decisions, phonological decisions) in visual word recognition.
      However, the functional connectivity underlying the task-related specialisation
      of regions in the left IFG is not yet well understood. In this study we
      investigated the neural mechanisms driving the interaction of WORD-TYPE (real
      word vs. pseudoword) and TASK (lexical vs. phonological decision) in Brodmann's
      area (BA) 45 in the left IFG using dynamic causal modelling (DCM). Four different
      models were compared, all of which included left BA44, left BA45, and left
      inferior temporal gyrus (ITG). In each model, the visual presentation of words
      and pseudowords is assumed to directly evoke activity in the ITG and is then
      thought to be subsequently propagated to BA45 and to BA44 via direct intrinsic
      connections. The models differed with regard to which connections were modulated
      by the different tasks. Both tasks were assumed to either modulate the ITG_BA45
      connection (Model #1), or the BA44_BA45 connection (Model #2), or both
      connections in parallel (Model #3). In Model #4 lexical decisions modulated the
      ITG_BA45 connection, whereas phonological decisions modulated the BA44_BA45
      connection. Bayesian model selection revealed a superiority of Model #1. In this
      model, the strength of the ITG_BA45 connection was enhanced during lexical
      decisions. This model is in line with the hypothesis that left BA 45 supports
      explicit lexical decisions during visual word recognition based on lexical access
      in the ITG.

PMID- 18095290
TI  - Optimization of HPLC-APCI-MS conditions for the qualitative and quantitative
      determination of total solanesol in tobacco leaves.
AB  - HPLC coupled online with atmospheric pressure chemical ionization MS (APCI-MS)
      technique was evaluated for the qualitative and quantitative determination of
      solanesol in extracts of tobacco leaves. The solanesol and other compounds in the
      extract were separated on an Alltima C(8) (4.6 mm x 250 mm) column with methanol
      and water (98:2 v/v) as mobile phase, with flow rate of 0.8 mL/min and UV
      detection wavelength of 211 nm. In the APCI(+) mode, abundant stable [M-H(2)O +
      H](+) ion (m/z at 613.5) was observed, with low abundance of other fragmentation
      ions. A comparison of APCI-MS and ESI-MS techniques showed that APCI mode is more
      sensitive than ESI mode, and thus better suited for solanesol analysis. When
      comparing UV 211 nm and APCI-MS in SIM for solanesol quantification, the former
      offered better precision and reproducibility, but the latter was more than 200
      times sensitive in detection. The developed method has been successfully applied
      to the analysis and comparison of solanesol concentration in different tobacco
      leaf samples.

PMID- 18095286
TI  - The Polycomb Group protein EZH2 regulates actin polymerization in human prostate
      cancer cells.
AB  - BACKGROUND: The Polycomb Group protein EZH2 is implicated in prostate cancer
      progression. EZH2 promotes prostate cancer cell proliferation and invasiveness.
      We describe a link between EZH2 function and actin polymerization in prostate
      cancer cells. METHODS: Nuclear and cytoplasmic EZH2 expression in benign and
      malignant prostate tissue samples was assessed. An association between EZH2
      function and actin polymerization in prostate cancer cells was investigated using
      siRNA-mediated knock-down of EZH2. Effects of EZH2 knock-down on actin
      polymerization dynamics were analyzed biochemically using immunoblot analysis of
      cell lysate fractions, and morphologically using immunocytochemistry. RESULTS:
      Cytoplasmic EZH2 is expressed at low levels in benign prostate epithelial cells
      and over-expressed in prostate cancer cells. Cytoplasmic EZH2 expression levels
      correlate with nuclear EZH2 expression in prostate cancer samples. Knock-down of
      EZH2 in PC3 prostate cancer cells increases the amount of F-actin polymerization,
      cell size, and formation of actin-rich filaments. CONCLUSIONS: Cytoplasmic EZH2
      is over-expressed in prostate cancer cells. EZH2 function promotes a reduction in
      the pool of insoluble F-actin in invasive prostate cancer cells. EZH2 may
      regulate actin polymerization dynamics and thereby promote prostate cancer cell
      motility and invasiveness.

PMID- 18095291
TI  - Capillary high performance liquid chromatography coupled with electrospray
      ionization mass spectrometry for rapid analysis of pinane monoterpene glycosides
      in Cortex Moutan.
AB  - In this study, a rapid and reliable assay has been developed for quantification
      of pinane monoterpene glycosides in cortex Moutan; it is based on capillary high
      performance liquid chromatography coupled with electrospray ionization mass
      spectrometry (capillary HPLC-ESI MS). This method utilizes capillary HPLC for the
      separation of seven pinane monoterpene glycosides in a methanol extract of the
      botanical sample followed by negative ion electrospray ionization and single ion
      monitoring (SIM). The compounds of interest in the sample were unambiguously
      identified on the basis of information about retention time and quasi-molecular
      ions ([M-H](-)) or adduct ions ([M+HCOO](-)). Validation parameters of the method
      were established. The linearity range was 1.01-105.5 microg/mL with the square of
      correlation coefficients lying in the range of 0.9965-0.9997, limits of detection
      were on the fmol level, the average recoveries varied between 91.8 and 101.0%,
      and good precision values (RSD, 1.2-4.91%) for peak area were obtained. After
      validation, the applicability of the method for determination of these pinane
      monoterpene glycosides in cortex Moutan has been demonstrated.

PMID- 18095292
TI  - Highlighting the role of the hydroxyl position on the alkyl spacer of
      hydroxypropyl-beta-cyclodextrin for enantioseparation in capillary
      electrophoresis.
AB  - This work investigates the resolving power of 2,3-dihydroxypropyl-beta-CD (2,3
      DHP-beta-CD) and 3-hydroxypropyl-beta-CD (3-HP-beta-CD) as chiral mobile phase
      additives (CMPAs) using CE. The effects of experimental parameters (CD
      concentration, buffer pH, and buffer concentration) on enantiorecognition were
      investigated. More than 20 basic chiral drugs were resolved with satisfactory
      enantioselectivity. Comparison with 2-hydroxypropyl-beta-CD (2-HP-beta-CD) showed
      that one or both of the two new chiral selectors show enhanced enantiorecognition
      for several molecules with bulky substitutes, such as Zopiclone and Mianserin,
      however, 2-HP-beta-CD has higher enantiorecognition for most of the analytes.
      Further studies on the structures of analytes and CMPAs showed that the OH moiety
      on the propyl spacer plays an important role in the separation of some chiral
      drugs.

PMID- 18095293
TI  - Kinetic and equilibrium study of the enantioseparation of paroxetine intermediate
      on amylose and tartaric acid-based chiral stationary phases.
AB  - trans-(-)-Paroxetine is a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor
      currently used as an antidepressant. trans-(+/-)-3-Ethoxycarbonyl-4-(4'
      fluorophenyl)-1-methylpiperidine-2,6-dione is an important intermediate of trans
      (-)-paroxetine. It was separated on amylose and tartaric acid-based chiral
      stationary phases by HPLC. The equilibrium constants and overall mass transfer
      coefficients together with the axial dispersion coefficients were experimentally
      determined by moment analysis based on the lumped kinetic model of
      chromatography. In case of Kromasil CHI-TBB, the equilibrium constants measured
      were found to be 8.36 and 9.37 for trans-(+) and trans-(-) enantiomers,
      respectively. For Chiralpak AD-H, the equilibrium constants were 6.68 and 4.13
      for trans-(+) and trans-(-) enantiomers, respectively. The axial dispersion
      coefficients of both enantiomers on Kromasil CHI-TBB column were about one order
      of magnitude greater than on Chiralpak AD-H. Fast kinetics of mass transfer in
      both chiral stationary phases was observed. Their overall mass transfer
      coefficients on Kromasil CHI-TBB and Chiralpak AD-H were 32.12, 33.18, 26.50,
      46.85 s(-1) for trans-(+) and trans-(-) enantiomers, respectively. The parameters
      obtained were utilized to simulate the elution profiles, and the simulated and
      experimental results match well, which confirmed that the parameters obtained in
      this study were valid.

PMID- 18095294
TI  - Validated reversed phase LC method for quantitative analysis of
      polymethoxyflavones in citrus peel extracts.
AB  - Polymethoxyflavones (PMFs), which exist exclusively in the citrus genus, have
      biological activities including anti-inflammatory, anticarcinogenic, and
      antiatherogenic properties. A validated RPLC method was developed for
      quantitative analysis of six major PMFs, namely nobiletin, tangeretin,
      sinensetin, 5,6,7,4'-tetramethoxyflavone, 3,5,6,7,3',4'-hexamethoxyflavone, and
      3,5,6,7,8,3',4'-heptamethoxyflavone. The polar embedded LC stationary phase was
      able to fully resolve the six analogues. The developed method was fully validated
      in terms of linearity, accuracy, precision, sensitivity, and system suitability.
      The LOD of the method was calculated as 0.15 microg/mL and the recovery rate was
      between 97.0 and 105.1%. This analytical method was successfully applied to
      quantify the individual PMFs in four commercially available citrus peel extracts
      (CPEs). Each extract shows significant difference in the PMF composition and
      concentration. This method may provide a simple, rapid, and reliable tool to help
      reveal the correlation between the bioactivity of the PMF extracts and the
      individual PMF content.

PMID- 18095296
TI  - Structural selection in G-quartet-based hydrogels and controlled release of
      bioactive molecules.
AB  - A guanosine-5'-hydrazide can entrap biologically interesting molecules such as
      acyclovir, vitamin C, and vancomycin into its hydrogel network. Controlled
      release of these molecules was monitored by 1H NMR spectroscopy. The hydrazide
      may potentially form mixed G-G quartets with analogous compounds containing a
      guanine group. 1H NMR spectroscopy was used to study the inclusion of various
      guanine derivatives into the hydrogel. The structural selectivity was found to
      depend strongly on both the shape and the charge of the additive and may arise
      from the strong cohesion of the supramolecular architecture of the gel and the
      resulting resistance to perturbation by foreign bodies. Hydrogels thus offer a
      promising medium for highly selective, controlled release of bioactive
      substances.

PMID- 18095298
TI  - The postoperative recurrence and the occurrence of second primary carcinomas in
      patients with early gastric carcinoma.
AB  - OBJECTIVE: Early gastric cancers have recently become more prevalent, and
      therefore, characterization of the features of patients who develop recurrence
      and second cancers is necessary for the development of effective postoperative
      follow-up strategies. METHODS: We evaluated the clinicopathological features and
      the timing of the development of both recurrence and second primary cancer after
      surgery for early gastric cancer in 671 patients. RESULTS: The incidence rate of
      recurrent early gastric cancer was 2.1%, and the incidence rate of second primary
      cancer was 4.8%, with an associated death rate of 3.3%. Most multiple primary
      cancers cases involved the colorectum and the lung. A multivariate analysis of
      overall survival identified multiple primary cancers, age, and sex as prognostic
      factors for early gastric cancer. The average interval from surgery to diagnosis
      of recurrence was identified as 3.4 +/- 2.1 years. The average interval for
      peritoneal recurrence was shorter than that for hematogenous recurrence (P <
      0.05). The average interval from diagnosis of early gastric cancer to diagnosis
      of the second primary cancer was 7.1 +/- 4.6 years. CONCLUSION: Patients with
      early gastric cancer, particularly patients who are males, elderly and have
      lymphatic involvement, tend to have a greater risk of developing a second primary
      cancer and recurrence, respectively.

PMID- 18095299
TI  - Unsuspected gallbladder cancer diagnosed during or after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: The long-term prognosis of laparoscopic cholecystectomy (LC) for
      patients with unsuspected gallbladder carcinoma (GBC) remains unclear. We
      investigated retrospectively the role of examination of frozen sections and the
      prognosis of patients with unsuspected GBC detected during or after LC. METHODS:
      LC was performed on 1,793 consecutive patients. If a suspicious lesion was found,
      intraoperative frozen section examination was performed. RESULTS: Of all these
      patients, 38 (2.1%) were histopathologically diagnosed as having a GBC during
      (28) or after LC (10). The tumor stages of the 28 diagnosed during LC were: pT1a
      (17), pT1b (2), pT2 (8), and pT3 (1). The sensitivity and specificity of
      intraoperative frozen section examination were 90 and 100%, respectively. On the
      other hand, those 10 cases diagnosed after LC had pT1a (1) and pT2 (9) tumors.
      Survival rates were not significantly affected by whether the patient was
      diagnosed with GBC during or after LC. CONCLUSIONS: The survival with unsuspected
      GBC was related to stage and it was confirmed that a carefully performed LC is
      adequate treatment for Stage 1A and B cancer. The LC procedure does not adversely
      affect the prognosis of unsuspected GBC, regardless of whether it is detected
      during or after LC.

PMID- 18095300
TI  - Prediction of microvascular invasion before curative resection of hepatocellular
      carcinoma.
AB  - BACKGROUND: The accurate staging of hepatocellular carcinoma (HCC) is important
      in establishing treatment strategies and prognosis. Among tumor factors,
      microvascular invasion, one of TNM staging components and prognostic factors, is
      underestimated preoperatively, due to inaccuracy of imaging modalities. We
      investigated preoperative predictors of microvascular invasion. METHODS: We
      reviewed 190 consecutive HCC patients given curative resection from 1999 to 2006.
      All were treatment-naive and monitored every 3 months after resection. Tumor
      recurrence, survivals, and clinicopathological factors associated with
      microvascular invasion were analyzed. RESULTS: The 5-year disease-free survival
      (DFS) rate was 39.4%(median follow-up duration: 35 months). On resection
      pathology, 38.9% (74/190 patients) had microvascular invasion undetected
      preoperatively, using liver spiral computed tomography (CT) or angiography.
      Independent predictors of microvascular invasion were tumor size (P = 0.043),
      number (P = 0.011), and Edmondson grade (P = 0.001). Patients with Edmondson
      grade 1 and size <5 cm had no microvascular invasion, while those with grade > or
      =2 had higher incidences (7/18 patients, 38.8%) even in small tumor (<2 cm). When
      tumors recurred, presence of microvascular invasion independently increased
      incidences of multiple tumors, portal vein invasion, and diffuse-infiltrative
      patterns significantly. CONCLUSIONS: Preoperative predictors of microvascular
      invasion are tumor size, number, and Edmondson grade, which may be useful for
      making clinical decisions in both non-surgical and surgical candidates.

PMID- 18095301
TI  - A 69-year-old male presenting with hypotension and anasarca.

PMID- 18095302
TI  - Recruitment of immature neutrophils in peripheral blood following
      leukocytapheresis therapy for rheumatoid arthritis.
AB  - The objective of this study is to evaluate the cellular mechanism underlying
      filtration leukocytapheresis (LCAP) therapy for the treatment of rheumatoid
      arthritis (RA). Thirteen patients with refractory RA each underwent three
      sessions of LCAP. Before (pre-) and after (post-) the completion of the first
      LCAP session, peripheral blood was sampled and analyzed for neutrophil surface
      markers using flow cytometry. The surface antigens of peripheral blood
      mononuclear cells (PBMCs) and neutrophils obtained at pre- and post-LCAP were
      then analyzed using a fluorescence-activated cell sorter. The American College of
      Rheumatology's criterion of a 20% improvement was achieved in six patients, but
      not in the other seven patients, after LCAP therapy. The post-LCAP number of
      blood band form neutrophils with a bone marrow phenotype (CD49d(dim+), low
      density) was higher among the responders than among the nonresponders, suggesting
      an association between the clinical response and the recruitment of bone-marrow
      derived neutrophils. After the nonspecific absorption of WBCs during a 1-h
      Cellsorba procedure, the number of PBMCs was consistently decreased, although the
      number of neutrophils that were affected by removal plus recruitment varied in a
      manner that was independent of efficacy. In contrast, the emergence of immature
      neutrophils in the peripheral blood was characteristic of the effective
      therapies. These cells were found after the 1st session of responders and also
      found following sessions of LCAPs. Immature neutrophils, which may be recruited
      from the bone marrow in the peripheral blood after the first session of LCAP, can
      predict the clinical efficacy of subsequent LCAP sessions.

PMID- 18095303
TI  - ABO-incompatible kidney transplantation-proposal of an intensified apheresis
      strategy for patients with high initial isoagglutinine titers.
AB  - Since Tyden's description of ABO-incompatible (ABOi) kidney transplantations
      based on antigen-specific immunoadsorption (IA) and rituximab (Tyden et al., Am J
      Transplant 2005;5:145-148), this technique has been successfully adopted by many
      transplant centers worldwide. The majority of centers strictly adhere to the
      Swedish protocol and perform IAs with a target volume of 1.5-2 plasma volumes on
      preoperative days -6, -5, -2, and -1, and postoperative days +3, +6, and +9,
      respectively. Patients who initially present with an IgG anti-A/B titer higher
      than 1:128 are not considered suitable candidates for ABOi transplantation by the
      Swedish protocol. Our center has gone beyond these suggestions and follows a
      slightly different strategy: We do not exclude patients with initial IgG anti-A/B
      titers higher than 1:128 and we perform as many preoperative antigen-specific
      extracorporeal treatments as needed to reach a threshold isoagglutinine titer of
      1:4 or less. To intensify isoagglutinine clearance preoperatively, the total
      target volume per treatment was increased to 2.5-3 plasma volumes.
      Preconditioning IAs are performed every other day, instead of daily.
      Postoperatively we perform IAs only, if titers mandate us to do so (Wilpert et
      al., Nephrol Dial Transplant 2007;22:3048-3051). We report on 11 "high-titer
      patients" who entered our ABOi kidney transplant program with initial titers of
      1:256 or above. Seven of 11 patients (64%) could successfully be transplanted
      with our modified ABO-apheresis protocol. Four of 11 high-titer patients did not
      reach target isoagglutinine titers of 1:4 or less and therefore did not undergo
      transplantation. We conclude that intensified preoperative IA renders a majority
      of high-titer patients suitable candidates for ABOi kidney transplantation.

PMID- 18095304
TI  - Improved peripheral blood stem cell collection following plasma exchange in a
      patient with elevated viscosity and coagulopathy.
AB  - We report a case of improved CD34+ cell yields from peripheral blood stem cell
      (PBSC) collection following therapeutic plasma exchange (TPE) in a patient with
      elevated viscosity and coagulopathy. The patient was a 46-year-old male diagnosed
      with IgM lambda multiple myeloma that was largely unresponsive to standard
      chemotherapy. He had coagulopathy due to lymphoproliferative disease-associated
      acquired von Willebrand Factor (vWF) deficiency. The patient underwent two rounds
      of PBSC collections over 3 consecutive weeks (five total collections) prior to
      planned tandem transplant for multiple myeloma. Both rounds resulted in poor
      collections due to processing difficulties. It was decided to perform three TPEs
      daily immediately prior to attempting additional PBSC collections, to treat the
      patient's elevated viscosity and thereby potentially improve the efficiency of
      collections. Immediately following the three TPEs, two additional PBSC
      collections resulted in sufficient CD34+ cells to proceed to transplant. Lower
      IgM and/or viscosity levels present after the three TPEs likely permitted
      successful collection of stem cells.

PMID- 18095305
TI  - Cytochrome P4502E1 sensitizes to tumor necrosis factor alpha-induced liver injury
      through activation of mitogen-activated protein kinases in mice.
AB  - The goal of this study was to evaluate the role of mitogen-activated protein
      kinase (MAPK) in cytochrome P4502E1 (CYP2E1) potentiation of lipopolysaccharide
      or tumor necrosis factor alpha (TNF-alpha)-induced liver injury. Treatment of
      C57/BL/6 mice with pyrazole (PY) plus lipopolysaccharide (LPS) induced liver
      injury compared with mice treated with PY or LPS alone. The c-Jun N-terminal
      kinase (JNK) inhibitor SP600125 or p38 MAPK inhibitor SB203580 prevented this
      liver injury. PY plus LPS treatment activated p38 MAPK and JNK but not
      extracellular signal-regulated kinase (ERK). PY plus LPS treatment triggered
      oxidative stress in the liver with increases in lipid peroxidation, decrease of
      glutathione (GSH) levels, and increased production of 3-nitrotyrosine adducts and
      protein carbonyl formation. This oxidative stress was blocked by SP600125 or
      SB203580. PY plus LPS treatment elevated TNF-alpha production, and this was
      blocked by SP600125 or SB203580. Neither SP600125 nor SB203580 affected CYP2E1
      activity or protein levels. Treating C57/BL/6 mice with PY plus TNF-alpha also
      induced liver injury and increased lipid peroxidation and decreased GSH levels.
      Prolonged activation of JNK and p38 MAPK was observed. All of these effects were
      blocked by SP600125 or SB203580. In contrast to wild-type SV 129 mice, treating
      CYP2E1 knockout mice with PY plus TNF-alpha did not induce liver injury, thus
      validating the role of CYP21E1 in this potentiated liver injury. Liver
      mitochondria from PY plus LPS or PY plus TNF-alpha treated mice underwent calcium
      dependent, cyclosporine A-sensitive swelling, which was prevented by SB203580 or
      SP600125. CONCLUSION: These results show that CYP2E1 sensitizes liver hepatocytes
      to LPS or TNF-alpha and that the CYP2E1-enhanced LPS or TNF-alpha injury, oxidant
      stress, and mitochondrial injury is JNK or p38 MAPK dependent.

PMID- 18095306
TI  - Acute viral hepatitis increases liver stiffness values measured by transient
      elastography.
AB  - Liver tissue alterations other than fibrosis may have an impact on liver
      stiffness measurement. In this study we evaluated 18 patients without a previous
      clinical history of liver disease, consecutively admitted for acute viral
      hepatitis. In each patient, aminotransferase determination and liver stiffness
      measurement were performed on the same study day, at 3 different points: (1) peak
      increase in aminotransferase; (2) aminotransferase 50% or less of the peak; (3)
      aminotransferase levels <or=2x the upper limit of normal. In all patients, the
      degree of liver stiffness at the time of the peak increase in aminotransferases
      exceeded the cutoff values proposed for the prediction of significant fibrosis or
      cirrhosis. A progressive significant reduction in liver stiffness values was
      observed (P < 0.0001) in the follow-up period in parallel with the reduction of
      aminotransferase levels (P < 0.0001). Moreover, a statistically significant,
      positive correlation between aminotransferases and liver stiffness measurement
      (LSM) at the onset of acute viral hepatitis was found (r = 0.53, P = 0.02 and r =
      0.51, P = 0.03 for alanine aminotransferase and aspartate aminotransferase,
      respectively). In conclusion, the extent of necroinflammatory activity needs to
      be carefully considered in future studies aimed at further validating transient
      elastography, particularly in patients with absent or low-stage liver fibrosis
      (in other words, F0-F2 METAVIR). LSM does not represent a reliable instrument to
      detect the presence of advanced fibrosis and cirrhosis in patients presenting
      with a clinical picture of acute hepatitis.

PMID- 18095307
TI  - Familiality and heritability of binge eating disorder: results of a case-control
      family study and a twin study.
AB  - OBJECTIVE: To estimate the familiality and heritability of binge eating disorder
      (BED). METHOD: We used a new ACE structural equation model to estimate
      heritability from a case-control family study of BED conducted in the Boston
      area. The sample consisted of 150 overweight/obese probands with lifetime BED by
      DSM-IV criteria, 150 overweight/obese probands without lifetime BED, and 888 of
      their first-degree relatives. We compared our findings with those from a study of
      binge eating (in the absence of compensatory behaviors) among 7,831 Norwegian
      twins. RESULTS: The prevalence of BED differed by sex and by age. In the case
      control family study, BED was found to aggregate in families, and heritability
      was estimated as 57% (CI: 30-77%). Including shared environment did not
      substantially improve the model's fit, nor did allowing sex-specific
      heritability. Findings from the twin study were similar. CONCLUSION: BED appears
      to aggregate in families and have a significant genetic component.

PMID- 18095308
TI  - Personality and eating behaviors: a case-control study of binge eating disorder.
AB  - OBJECTIVE: Questions have been raised about the validity of binge eating disorder
      (BED) as psycho-pathologically distinct from other forms of overeating. Our
      purpose was to ascertain whether BED individuals differed in important ways from
      nonbinging obese adults. METHOD: BED adults were recruited from the community as
      were weight-matched (obese) and normal-weight control (NWC) groups. All groups
      were equivalent for age and gender distribution, and were assessed on several
      personality traits and eating behaviors. RESULTS: BED individuals and obese
      controls did not differ on the personality traits. Both were more reward
      sensitive, and had greater anxiousness, impulsivity, and addictive personality
      traits than NWC. However, BED individuals reported significantly greater hedonic
      eating compared with the obese, who had higher levels than NWC. CONCLUSION: Our
      findings provided no evidence of a psychological identity unique to obese adults
      with BED although their eating behaviors are markedly hedonically driven-i.e.,
      more responsive to factors external to physiological needs.

PMID- 18095309
TI  - The quality of treatment of eating disorders: a comparison of the therapists' and
      the patients' perspective.
AB  - OBJECTIVE: The aims of this study were to investigate the quality of treatment of
      eating disorders (EDs) from the therapists' and patients' perspective and to
      compare their views. METHOD: The Questionnaire for Eating Problems and Treatment
      (QEPT) was administered to 73 therapists working with patients with ED, to 156
      current ED and 148 former ED patients. The QEPT addresses the quality of
      treatment of EDs. ED diagnosis was assessed by the Eating Disorder Examination
      Questionnaire. Answers were analyzed quantitatively and qualitatively. RESULTS:
      Both therapists and patients most often mentioned focus of treatment, therapeutic
      alliance, and communicational skills as important aspects of the quality of
      treatment. However, they valued similar topics differently. Therapists valued the
      focus on ED symptoms and behavioral change more highly, whereas patients
      underscored the importance of the therapeutic relationship and addressing
      underlying problems. Most therapists work from a cognitive behavioral
      orientation, but protocol-based treatment was not found important. CONCLUSION:
      There is an avid need for dissemination of evidence-based treatment. Therapists'
      and patients' views supplement current evidence-based knowledge on treatment
      quality of EDs. Optimal treatment of EDs will be facilitated when these three
      bodies of knowledge-the available evidence and the therapists' and patients'
      views-are integrated.

PMID- 18095310
TI  - An empirical study of the typology of bulimic symptoms in young Portuguese women.
AB  - OBJECTIVE: To investigate whether clusters of bulimic symptoms exist in a
      community sample of young Portuguese women. METHOD: A total of 2028 females, aged
      12-23 years, completed the Eating Disorder Examination Questionnaire (EDE-Q).
      Latent class analysis was applied to the seven bulimic symptoms, age, and body
      mass index. RESULTS: The selected 4-class solution yielded a "healthy" class,
      reporting minimal binge eating and purging behaviors. A "binge eating" class,
      resembled binge eating disorder. A "purging" class had infrequent binge eating,
      but frequent compensatory behaviors. Finally, in a "classic bulimia nervosa"
      class, binge eating episodes were reported by 95% of participants, and
      compensatory behaviors were frequently endorsed. EDE -Q global and subscale
      scores differed across all latent classes. CONCLUSION: In the community, three
      natural patterns exist: binge eating plus compensatory behaviors, binge eating
      only, and purging in the absence of binge eating. These results have implications
      for future revisions of eating disorders nosology.

PMID- 18095311
TI  - The duration of severe insulin omission is the factor most closely associated
      with the microvascular complications of Type 1 diabetic females with clinical
      eating disorders.
AB  - OBJECTIVE: To investigate which features of eating disorders are associated with
      retinopathy and nephropathy in Type 1 diabetic females with clinical eating
      disorders. METHOD: Participants were 109 Type 1 diabetic females with clinical
      eating disorders diagnosed by the structured clinical interview for DSM-IV
      (bulimia nervosa [n = 70], binge-eating disorder [n = 28], anorexia nervosa [n =
      7], and eating disorder not otherwise specified [n = 4]). Retinopathy and
      nephropathy were screened and demographic, medical, and eating disorder related
      factors were investigated. To identify the factors associated with each
      complication, logistic regression analysis was done. RESULTS: Duration of severe
      insulin omission and duration of Type 1 diabetes were significantly associated
      with retinopathy (odds ratios = 1.35 and 1.23, respectively) and nephropathy
      (odds ratio = 1.35 and 1.21, respectively) in multivariate regression analyses.
      CONCLUSION: Of the various problematic behavioral factors related to eating
      disorders, the duration of severe insulin omission was the factor most closely
      associated with the retinopathy and nephropathy of Type 1 diabetic females with
      clinical eating disorders by multivariate analysis. This finding may help
      patients who deliberately omit insulin become aware of medical risk of insulin
      omission.

PMID- 18095312
TI  - Impact of maternal circulating cholesterol and gestational diabetes mellitus on
      lipid metabolism in human term placenta.
AB  - Maternal hypercholesterolemia (HC) during pregnancy and gestational diabetes
      mellitus (GDM) are associated with disturbance of fetal development which may
      also modify key features of placental functions. In this study, we evaluated the
      impact of maternal hypercholesterolemia on placental cholesterol and lipid
      metabolism in 59 women classified in two groups according to the median
      concentration of plasma total cholesterol (6.42 mM). The impact of GDM was also
      evaluated on the metabolism of placentas obtained from 7 insulin-treated GDM and
      7 non-GDM women. We showed that high maternal circulating cholesterol is
      associated with a significant increase in the LDL-cholesterol, ApoB-100 and
      triglyceride concentrations in the maternal blood. However the level of
      cholesterol in the venous cord blood and placenta remains unchanged in response
      to modification in maternal cholesterol profile. The levels of Fatty acid
      synthase (FAS) and SREBP-2 expressions in placenta are significantly increased in
      the HC group while expression of both sterol regulatory element-binding proteins
      1 (SREBP-1) and HMG-CoA reductase (HMGR) are not modified. GDM is not associated
      with modification in the maternal lipid profile but it increases the
      concentration of inflammatory cytokines (IL-1beta and TNF-alpha) in placenta
      which correlates with a dramatic induction of FAS expression without affecting
      the expression of mature SREBPs proteins. In conclusion, our study suggests that
      in placenta, expressions of key proteins involved in de novo lipid synthesis are
      affected by changes in maternal metabolism (HC and GDM) that may subsequently
      affect fetal development.

PMID- 18095313
TI  - Molecular cloning of Plk1 and Nek2 and their expression in mature gonads of the
      teleost fish Nile tilapia (Oreochromis niloticus).
AB  - Polo-like kinase 1 (Plk1) and NIMA-related kinase 2 (Nek2) are serine/threonine
      kinases that are involved in the G2/M phase transition of the cell cycle in
      vertebrates. Although they also play critical roles in the regulation of
      spermatogenesis and oogenesis, their characterization in meiosis has not been
      elucidated fully, particularly in teleost fish. To investigate the evolutionary
      significance of serine/threonine kinases in the reproductive system of fish, we
      cloned the cDNAs of Plk1 and Nek2 from a Nile tilapia (Oreochromis niloticus)
      testicular cDNA library. Tilapia Plk1 encodes a protein of 582 amino acids that
      shares 75% homology with human Plk1, while tilapia Nek2 encodes a putative
      protein of 446 amino acids that shares 70% homology with human Nek2. Analyses of
      tissue distribution by RT-PCR and Southern blotting revealed that Plk1 and Nek2
      are strongly expressed in the ovary and testis. Northern blot analysis revealed
      two Nek2 transcripts in the ovary and testis with different expression patterns,
      which indicates the presence of two structural variants for tilapia Nek2.
      Moreover, the localization of Plk1 and Nek2 mRNAs in tilapia gonads was
      determined by in situ hybridization analysis. In the ovary, Plk1 and Nek2 were
      expressed predominantly in oocytes. In the testis, on the other hand, Plk1 was
      expressed in primary spermatocytes, while Nek2 was generally expressed in primary
      and secondary spermatocytes. These results suggest that Plk1 and Nek2 are key
      factors in the progression of meiosis in fish.

PMID- 18095314
TI  - Qualitative and quantitative differences of cytoskeleton proteins in embryos
      produced in vitro, in vivo, and by somatic nuclear transfer.
AB  - The cytoskeleton, consisting of complex and dynamic systems of structural
      filaments, intermediate filaments and microtubules, is not only a structural
      element but also contributes to many cellular processes such as functional
      compartments, transportation, mitosis, secretion, formation of cell extensions,
      and intercellular communication. Suggestions in rat 2-cell embryos that abnormal
      distributions of cytoskeletal proteins occurred following the initiations of
      developmental arrest and our former studies showing reduced intercellular contact
      zones in cloned bovine embryos prompted us to conduct comparative studies on 8
      cell stage bovine embryos from nuclear transfer (NT), in vitro, and in vivo
      production. Immunohistochemistry and Laser-Scanning-Microscopy facilitated
      detection of cytoskeleton proteins--alpha-tubulin, F-actin, beta-catenin, and the
      cell adhesion protein cadherin; image and cluster analysis were subsequently used
      to study the distribution pattern of the proteins, whereas Western blot was
      carried out for their qualitative and quantitative analysis. The maximum
      fluorescence intensity of stained alpha-tubulin was observed in the cloned and
      the in vitro embryos. A significant higher intensity of staining for F-actin was
      observed in the in vivo and in vitro embryos. In contrast, Western blot revealed
      no differences of actin, tubulin, and catenin between the three tested groups
      whereas a lower abundance of cadherin proteins in the cloned embryos was visible.
      The distribution of actin filaments in cloned embryos was more centric or one
      sided and not peripheral whereas the stained spots of catenin were smaller in
      comparison to in vivo or in vitro produced embryos. These differences recorded in
      the distribution patterns may be associated with cell physiological processes
      related to an influenced actin-catenin-cadherin system. In conclusion, reduced
      intercellular contacts coupled with abnormal distribution of cytoskeletal
      proteins seem to play an important role in the developmental arrest encountered
      normally at the 8-cell stage in bovine cloned embryos.

PMID- 18095315
TI  - Analysis of recurrent event data under the case-crossover design with
      applications to elderly falls.
AB  - The case-crossover design is useful for studying the effects of transient
      exposures on short-term risk of diseases or injuries when only data on cases are
      available. The crossover nature of this design allows each subject to serve as
      his/her own control. While the original design was proposed for univariate event
      data, in many applications recurrent events are encountered (e.g. elderly falls,
      gout attacks, and sexually transmitted infections). In such situations, the
      within-subject dependence among recurrent events needs to be taken into account
      in the analysis. We review three existing conditional logistic regression (CLR)
      based approaches for recurrent event data under the case-crossover design. A
      simple approach is to use only the first event for each subject; however, we
      would expect loss of efficiency in estimation. The other two reviewed approaches
      rely on independence assumptions for the recurrent events, conditionally on a set
      of covariates. Furthermore, we propose new methods that adjust the CLR using
      either a within-subject pairwise resampling technique or a weighted estimating
      equation. No specific dependency structure among recurrent events is needed
      therein, and hence, they have more flexibility than the existing methods in the
      situations with unknown correlation structures. We also propose a weighted Mantel
      Haenszel estimator, which is easy to implement for data with a binary exposure.
      In simulation studies, we show that all discussed methods yield virtually
      unbiased estimates when the conditional independence assumption holds. These
      methods are illustrated using data from a study of the effect of medication
      changes on falls among the elderly.

PMID- 18095316
TI  - New global map of Crohn's disease: Genetic, environmental, and socioeconomic
      correlations.
AB  - Seventy-five years after the initial characterization of Crohn's disease (CD),
      much remains obscure about its etiology. The authors sought to evaluate the
      incidence trends of the last 25 years worldwide, and the existence of potential
      correlations with genetic, environmental, and socioeconomic factors that could be
      etiologically implicated in the pathogenesis of CD. Relevant medical literature
      for individual countries on the incidence of CD, on the incidence of associated
      genetic mutations, and on the incidence of suggested etiologic infectious agents
      such as Mycobacterium avium paratuberculosis were retrieved from published
      medical literature, reports from relevant international congresses, and through
      official reports from national health authorities. Increasing trends have been
      observed almost worldwide, with a broad north-south gradient still prevailing in
      Europe. Distinct regions of New Zealand, Canada, Scotland, France, the
      Netherlands, and Scandinavia represent the highest incidence areas.
      Industrialized status and affluence are the common denominators between endemic
      areas, but are too broad as terms to strongly indicate any particular etiological
      role. The increasing trends observed in Asia still account for a low prevalence
      of the disease and may represent increased detection and diagnostic ability of
      local health systems. Genetic associations are variably reproduced worldwide, in
      a manner inconsistent with a strong etiologic relationship. Data on
      paratuberculosis incidence are scarce, and the existing ones are ambivalent
      regarding an even indirect correlation between CD and an infectious trigger.

PMID- 18095317
TI  - Serum biomarkers in a mouse model of bacterial-induced inflammatory bowel
      disease.
AB  - BACKGROUND: The diagnosis and classification of inflammatory bowel disease (IBD)
      require both clinical and histopathologic data. Serum biomarkers would be of
      considerable benefit to noninvasively monitor the progression of disease, assess
      effectiveness of therapies, and assist in understanding disease pathogenesis.
      Currently, there are limited noninvasive biomarkers for monitoring disease
      progression in animal IBD models, which are used extensively to develop new
      therapies and to understand IBD pathogenesis. METHODS: Serum biomarkers of early
      and late IBD were identified using multianalyte profiling in mdr1a(-/-) mice with
      IBD triggered by infection with Helicobacter bilis. The correlation of changes in
      these biomarkers with histopathology scores and clinical signs in the presence
      and in the absence of antibiotic treatment was determined. RESULTS: Serum levels
      of interleukin (IL)-11, IL-17, 10-kDa interferon-gamma-inducible protein (IP-10),
      lymphotactin, monocyte chemoattractant protein (MCP)-1, and vascular cell
      adhesion molecule (VCAM)-1 were elevated early in IBD. In late, more severe IBD,
      serum levels of IL-11, IP-10, haptoglobin, matrix metalloproteinase-9, macrophage
      inflammatory protein (MIP)-1gamma, fibrinogen, immunoglobulin A, MIP-3 beta
      (beta), VCAM-1, apolipoprotein (Apo) A1, and IL-18 were elevated. All late serum
      biomarkers except Apo A1 correlated with histopathology scores. Antibiotic
      treatment improved clinical signs of IBD and decreased mean serum values of many
      of the biomarkers. For all biomarkers, the individual pathology scores correlated
      significantly with individual serum analyte levels after treatment. CONCLUSIONS:
      Serum analyte measurement is a useful, noninvasive method for monitoring disease
      in a mouse model of bacterial-induced IBD.

PMID- 18095318
TI  - Another anti-TNF therapy for patients with Crohn's disease.

PMID- 18095319
TI  - Characteristics and survival of 750 children diagnosed with a renal tumor in the
      first seven months of life: A collaborative study by the SIOP/GPOH/SFOP, NWTSG,
      and UKCCSG Wilms tumor study groups.
AB  - BACKGROUND: To review the clinical characteristics and survival of infants
      diagnosed with a primary renal tumor in the first 7 months of life. PROCEDURE: A
      retrospective data review of patients registered in five large international
      protocols (SFOP/GPOH/SIOP9/93-01, UKW3 and NWTSG 4 and 5) spanning 1985-2002.
      RESULTS: 750 (7.2%) of 10,430 registered patients were diagnosed with a renal
      tumor before age 213 days. Tumor types were Wilms tumor (WT) 58%; congenital
      mesoblastic nephroma (CMN) 18%; malignant rhabdoid tumor (MRTK) 8%; clear cell
      sarcoma (CCSK) 2%; non-Wilms tumor (unspecified) 6%; histology unknown, 9%. CMN
      predominated among tumors diagnosed in the first month of life (54%) but its
      relative contribution diminished to <10% of all cases diagnosed after the age of
      3 months (P < 0.001). Among 639 cases with specified histology and stage, 9/11
      stage IV tumors were MRTK, 37/39 bilateral tumors were WT. In 626 children where
      surgical approach was specified, 522 had immediate nephrectomy. For all cases, 5
      years event-free survival (EFS) was 80% and overall survival (OS) 86%. Five years
      EFS and OS respectively by tumor type were WT (86%, 93%), CMN (94%, 96%), CCSK
      (49%, 51%), MRTK (16%, 16%). CONCLUSION: Renal tumors diagnosed in the first 7
      months of life generally have an excellent prognosis though histology is an
      important prognostic factor. In the first 2 months of life the prevalence of CMN
      is high. The relative occurrence of WT increases rapidly with age thereafter.
      Bilateral tumors are usually WT. Tumors with metastases at diagnosis are usually
      MRTK.

PMID- 18095320
TI  - Neurons controlling jumping in froghopper insects.
AB  - The neurons innervating muscles that deliver the enormous power enabling
      froghopper insects to excel at jumping were revealed by backfilling the nerves
      from those muscles. The huge trochanteral depressor muscle (M133) of a hind leg
      consists of four parts. The two largest parts (M133b,c) occupy most of the
      metathorax and are innervated by the same two motor neurons that have small,
      laterally placed somata in the metathoracic ganglion and axons in nerve N3C(2).
      They are also supplied by three dorsal unpaired median (DUM) neurons with the
      largest diameter somata in the central nervous system. A small metathoracic part
      of the muscle (M133d) is supplied by two motor neurons with lateral somata and by
      common inhibitory motor neuron CI(1), all with axons in nerve N3C(3) The motor
      neuron with the larger soma has a thick primary neurite that projects across the
      midline of the ganglion so that its branches overlap those of its symmetrical
      counterpart,innervating the same muscle of the other hind leg. The fourth coxal
      part of the muscle (M133a) is innervated by two motor neurons (one with a ventral
      and the other with a dorsal and lateral soma), by CI(1), and by a DUM neuron with
      a small soma. All have axons in nerve N5A. The two trochanteral levator muscles
      of a hind leg are contained within the coxa and are separately innervated by
      nerves N3B and N4, respectively. The properties of the different motor neurons
      are discussed in the context of the neural patterns that generate jumping.

PMID- 18095321
TI  - Olfactory sensory neuron-specific and sexually dimorphic expression of
      protocadherin 20.
AB  - Olfactory sensory axons navigate from the nasal cavity to the olfactory bulb and
      sort from among 1,000 different odorant receptor-expressing types to converge
      upon the same two or three glomeruli. To achieve this task during development, it
      is likely that multiple classes of regulatory molecules, including cell adhesion
      molecules, are involved. Cell adhesion molecules have been shown to be important
      in controlling axon guidance, fasciculation, and synapse formation. To gain
      further understanding of the involvement of adhesion molecules in olfactory
      circuitry development, we examined the dynamic and cell type specific expression
      of a novel protocadherin, PCDH20, in the olfactory system. PCDH20 is specifically
      expressed in newly differentiated olfactory sensory neurons and their axons
      during development. PCDH20 expression is down-regulated in the adult olfactory
      system, except in a small olfactory sensory neuron population. These small,
      discrete numbers of PCDH20-positive glomeruli in the adult olfactory bulb are
      consistently clustered in the ventral-caudal region in both male and female mice.
      However, adult males have higher numbers of PCDH20-positive glomeruli with a
      broader distribution, whereas adult females have fewer PCDH20-positive glomeruli
      with a more restricted distribution. The gender difference in PCDH20 expression
      may reflect olfactory receptor expression differences for gender-specific social
      discrimination.

PMID- 18095322
TI  - Type 4 OFF cone bipolar cells of the mouse retina express calsenilin and contact
      cones as well as rods.
AB  - Immunocytochemical discrimination of distinct bipolar cell types in the mouse
      retina is a prerequisite for analyzing retinal circuitry in wild-type and
      transgenic mice. Here we demonstrate that among the more than 10 anatomically
      defined mouse bipolar cell types, type 4 bipolar cells are specifically
      recognized by anti-calsenilin antibodies. Axon terminals in the inner plexiform
      layer are not readily identifiable because calsenilin is also expressed in a
      subset of amacrine and ganglion cells. In contrast, in the outer plexiform layer
      calsenilin immunoreactivity allows the analysis of photoreceptor to type 4
      bipolar cell contacts. A dense plexus of calsenilin-positive dendrites makes
      several basal contacts at cone pedicles. An individual calsenilin-positive
      bipolar cell contacts five to seven cones. In addition, some calsenilin-positive
      dendrites contact rod photoreceptors. On average we counted 10 rod spherule
      contacts per type 4 bipolar cell, and approximately 10% of rods contacted type 4
      bipolar cells. We suggest that type 4 bipolar cells, together with the recently
      described type 3a and b cells, provide an alternative and direct route from rods
      to OFF cone bipolar cells. In the Bassoon DeltaEx4/5 mouse, a mouse mutant that
      shows extensive remodeling of the rod system including sprouting of horizontal
      and rod bipolar cells into the outer nuclear layer due to impaired synaptic
      transmission, we found that in addition mixed-input (type 3 and 4) OFF bipolar
      cells sprout to ectopic sites. In contrast, true cone-selective type 1 and 2 OFF
      cone bipolar cells did not show sprouting in the Bassoon mouse mutant.

PMID- 18095323
TI  - Expression of calcium channel CaV1.3 in cat spinal cord: light and electron
      microscopic immunohistochemical study.
AB  - In spinal neurons, plateau potentials serve to amplify neuronal input signals. To
      a large extent, the underlying persistent inward current is mediated by a subtype
      of the L-type calcium channel (Ca(V)1.3). In the present investigation, we have
      studied its distribution and cellular localization in the cat spinal cord by
      light and electron microscopic immunohistochemistry. The results show that
      Ca(V)1.3-like immunoreactivity is widely distributed in all segments of the
      spinal cord but that the distribution in the different laminae of the spinal gray
      matter varies, with the highest density of labeled neurons in lamina IX and the
      lowest in lamina II. The labeling intensity was highest in neuronal somata, but a
      certain length of the proximal dendrite was also labeled. Some neuronal groups
      exhibited a particularly dense labeling; these include the lateral motoneuronal
      group in the cervical and the lumbar enlargements and the phrenic nucleus in
      cervical, Clarke's nucleus in lower thoracic and upper lumbar, and Onuf's nucleus
      in upper sacral segments. At the ultrastructural level, Ca(V)1.3-immunoreactive
      products were found in neuronal somata and dendrites of different sizes. In the
      soma, they were predominantly associated with the rough endoplasmic reticulum but
      some also with the plasma membrane. In dendrites, they were associated with both
      intracellular organelles, including microtubules and microchondria, and the
      plasma membrane. These results indicate that significant proportions of the
      neurons in cat spinal cord, including projection neurons, interneurons, and
      motoneurons, are endowed with ion channels that subserve persistent inward
      currents and act to amplify synaptic input signals.

PMID- 18095324
TI  - Ultrastructure and synaptic differences of the boutons of the projection neurons
      between the lip and collar regions of the mushroom bodies in the ant, Cataglyphis
      albicans.
AB  - The mushroom bodies of insects are viewed as key neuropils for sensory
      integration and perhaps learning and memory. In Hymenoptera, particularly ants,
      the calyx of the mushroom bodies is divided into two main regions, the lip and
      the collar. Although most ants are highly dependent on olfaction and have
      enlarged calyces comprised mostly of lip, some ant groups are also highly visual
      and have well-developed collars. The desert ant Cataglyphis albicans, known for
      its navigational abilities, shifts from the dark olfactory demanding nest
      interior to the visually demanding desert environment, and unlike many other ants
      their mushroom bodies are comprised of both a well-developed lip and collar. In
      this study, using electron microscope serial-sectioning and 3D-reconstructions,
      we show that axonal processes that innervate the lip and collar are inherently
      different in structure and synaptic connectivity. The boutons of the lip are
      larger, with more synaptic vesicles and larger synapses than the collar, while
      boutons of the collar have more postsynaptic partners per synapse. Our
      morphological findings suggest that the signals originating from olfactory
      projection neurons that innervate the lip appear stronger and more likely to
      propagate than signals that innervate the collar, while the signals entering the
      collar appear relatively weaker and are further integrated between more
      postsynaptic partners. We discuss the differences of the signaling properties
      between the lip and collar projection neurons and suggest that the greater
      postsynaptic integration in the collar is presumably for spatial processing for
      visual navigation in Cataglyphis.

PMID- 18095325
TI  - Persistent stickiness of viscous capture threads produced by araneoid orb-weaving
      spiders.
AB  - The most commonly encountered spider orb-webs rely on sticky, viscous capture
      threads to retain prey. These threads are composed of supporting fibers covered
      by a complex aqueous solution that forms a series of droplets, each with a
      glycoprotein granule that confers adhesion. This adhesive system normally
      functions for less than a day before being replaced. Despite their ephemeral
      nature, we found that the stickiness of viscous threads persists for much longer.
      When measured over the course of 7 days, small decreases in the adhesion of
      Larinioides cornutus threads were not statistically significant. Threads of
      Araneus marmoreus, Argiope trifasciata, and Metepeira labyrinthea were aged for 8
      10 months and remeasured under environmental conditions similar to those under
      which initial measurements were made. When returned to humidity similar to that
      under which measurements were initially made, neither the droplet volumes nor the
      stickiness of aged threads differed significantly from those of newly spun
      threads. These observations indicate that when viscous threads are protected from
      contamination, the compounds responsible for their hydrophilic and adhesive
      properties do not degrade easily.

PMID- 18095326
TI  - Development of body condition in hinds of Iberian red deer during gestation and
      its effects on calf birth weight and milk production.
AB  - Reproductive effort affects body reserves and subsequent ability to reproduce. In
      fact, the energy costs of gestation and lactation in hinds of red deer have a
      marked effect on maternal condition. The objectives of this study were to examine
      the development of hind monthly body condition during gestation in relation to
      reproductive rest, age and age class, just as its effects on total milk yield and
      calf birth weight. Eighty hinds of Iberian red deer were used as subjects during
      2 years of study. They had ad libitum access to food and water. Animals were
      weighed weekly, and body condition was individually assessed. Milking was carried
      out under anesthesia with a milking machine followed by hand milking to collect
      the remaining milk. Age and reproductive rest influenced body condition,
      improving with age (coefficient: 0.10+/-0.01; P<0.001) and reproductive rest
      (mean+/-SEM, 3.75+/-0.05 vs. 3.25+/-0.02, with and without rest respectively;
      P<0.001). Hind age correlated positively with her body condition (R=0.62,
      P<0.001), however, when age class was included in the model, age was not
      significant. The greater the age class (up to age class 4) the greater the body
      condition; however, hinds of age class 5 had a lower body condition, but no
      significant differences were observed. Development of the body condition during
      gestation was different to age class 1 with respect to the others, just as
      between hinds that rested the preceding year and those that did not.

PMID- 18095327
TI  - The gamma-H2A.X: is it just a surrogate marker of double-strand breaks or much
      more?
AB  - In recent years, several histone modifications have been implicated in the
      cellular response to DNA double-strand breaks (DSBs). One of the best
      characterized histone modifications important in DSB repair is the
      phosphorylation of histone H2A variant, H2A.X. In response to DSBs, H2A.X is
      phosphorylated and this phosphorylation is required for DSB signaling and the
      retention of repair proteins at the break site. Despite the existing picture that
      the function of H2A.X is to promote DNA repair, very recent data suggest that the
      phosphorylation of histone H2A.X has additional functions. This is analogous to
      histone H3 phosphorylation on serine 10, which participates in seemingly
      incompatible functions--transcriptional activation and mitosis. In this review,
      we discuss the role of histone H2A.X in maintaining genomic stability and review
      emerging evidence that histone H2A.X is multifunctional.

PMID- 18095328
TI  - Characteristics of the adaptive response in cultured salmon cells exposed to
      ionizing radiation.
AB  - The aim of this study was to investigate the influence of "priming" doses of
      ionizing irradiation on salmon cell survival in vitro prior to being challenged
      with subsequent higher doses. A radiation-induced adaptive response (AR) was
      examined in the Chinook salmon embryo cell line (CHSE-214). Cells were initially
      irradiated with a range of priming (conditioning) doses of (60)Co gamma (gamma)
      rays (0.25-0.75 Gy), followed by a challenge dose of 7.50 Gy at intervals of 24,
      48, and 72 hr. The AR was assessed using a colony-forming assay. Cell survival
      was determined by counting the number of colonies (viable clones) after 40 days
      of culture. This study revealed that cells that received a priming dose of 0.50
      Gy before delivering the higher challenge dose became more radiation resistant
      with an increase in cell survival of 29% over cells receiving the challenge dose
      alone. The cells showed maximum resistance to ionizing radiation when the priming
      dose was given 72 hr prior to the higher challenge dose. This study is one of the
      first to demonstrate an AR using an in vitro piscine system, and is generally
      consistent with other studies of both in vitro and in vivo systems across the
      taxa.

PMID- 18095330
TI  - The social environment and the epigenome.
AB  - The genome is programmed by the epigenome. Two of the fundamental components of
      the epigenome are chromatin structure and covalent modification of the DNA
      molecule itself by methylation. DNA methylation patterns are sculpted during
      development and it has been a long held belief that they remain stable after
      birth in somatic tissues. Recent data suggest that DNA methylation is dynamic
      later in life in postmitotic cells such as neurons and thus potentially
      responsive to different environmental stimuli throughout life. We hypothesize a
      mechanism linking the social environment early in life and long-term epigenetic
      programming of behavior and responsiveness to stress and health status later in
      life. We will also discuss the prospect that the epigenetic equilibrium remains
      responsive throughout life and that therefore environmental triggers could play a
      role in generating interindividual differences in human behavior later in life.
      We speculate that exposures to different environmental toxins alters long
      established epigenetic programs in the brain as well as other tissues leading to
      late-onset disease.

PMID- 18095329
TI  - Intersection of nuclear receptors and the proteasome on the epigenetic landscape.
AB  - Nuclear receptors (NRs) represent a class of transcription factors that associate
      with both positive and negative chromatin modifying complexes to activate or
      repress gene transcription. The 26S proteasome plays a major role in NR-regulated
      gene transcription by tightly regulating the levels of the receptor and
      coregulator complexes. Recent evidence suggests a robust nonproteolytic role for
      specific proteasome subunits in gene transcription mediated via alterations in
      specific histone modifications. The involvement of nuclear receptors and the
      proteasome with chromatin modifying complexes or proteins, particularly those
      that modify DNA and histone proteins, provides an opportunity to review two
      critical epigenetic mechanisms that control gene expression and heritable
      biological processes. Both nuclear receptors and the proteasome are targets of
      environmental factors including some which lead to epigenetic changes that can
      influence human diseases such as cancer. In this review, we will explore
      molecular mechanisms by which NR-mediated gene expression, under the control of
      the proteasome, can result in altered epigenetic landscapes.

PMID- 18095335
TI  - Influence of ammonium chloride feeding time and light intensity on the
      cultivation of Spirulina (Arthrospira) platensis.
AB  - This study dealt with the influence of both the feeding time and light intensity
      on the fed-batch culture of the cyanobacterium Spirulina (Arthrospira) platensis
      using ammonium chloride as a nitrogen source. For this purpose, a 2(2) plus star
      central composite experimental design combined with response surface methodology
      was employed, and the maximum cell concentration (X(m)), the cell productivity
      (P(X)), and the yield of biomass on nitrogen (Y(X/N)) were selected as the
      response variables. The optimum values of X(m) (1,833 mg L(-1)) and Y(X/N) (5.9 g
      g(-1)) estimated by the model at light intensity of 13 klux and feeding time of
      17.2 days were very close to those obtained experimentally under these conditions
      (X(m) = 1,771 +/- 41 mg L(-1); Y(X/N) = 5.7 +/- 0.17 g g(-1)). The cell
      productivity was a decreasing function of the ammonium chloride feeding time and
      a quadratic function of the light intensity. The protein and lipid contents of
      dry biomass collected at the end of cultivations were shown to decrease with
      increasing light intensity.

PMID- 18095336
TI  - Identification of metabolic fluxes in hepatic cells from transient 13C-labeling
      experiments: Part II. Flux estimation.
AB  - This contribution addresses the identification of metabolic fluxes and metabolite
      concentrations in mammalian cells from transient (13)C-labeling experiments.
      Whilst part I describes experimental set-up and acquisition of required
      metabolite and (13)C-labeling data, part II focuses on setting up network models
      and the estimation of intracellular fluxes. Metabolic fluxes were determined in
      glycolysis, pentose-phosphate pathway (PPP), and citric acid cycle (TCA) in a
      hepatoma cell line grown in aerobic batch cultures. In glycolytic and PPP
      metabolite pools isotopic stationarity was observed within 30 min, whereas in the
      TCA cycle the labeling redistribution did not reach isotopic steady state even
      within 180 min. In silico labeling dynamics were in accordance with in vivo (13)C
      labeling data. Split ratio between glycolysis and PPP was 57%:43%; intracellular
      glucose concentration was estimated at 101.6 nmol per 10(6) cells. In contrast to
      isotopic stationary (13)C-flux analysis, transient (13)C-flux analysis can also
      be applied to industrially relevant mammalian cell fed-batch and batch cultures.

PMID- 18095337
TI  - Identification of metabolic fluxes in hepatic cells from transient 13C-labeling
      experiments: Part I. Experimental observations.
AB  - An experimental set-up for acquiring metabolite and transient (13)C-labeling data
      in mammalian cells is presented. An efficient sampling procedure was established
      for hepatic cells cultured in six-well plates as a monolayer attached to
      collagen, which allowed simultaneous quenching of metabolism and extraction of
      the intracellular intermediates of interest. Extracellular concentrations of
      glucose, amino acids, lactate, pyruvate, and urea were determined by GC-MS
      procedures and were used for estimation of metabolic uptake and excretion rates.
      Sensitive LC-MS and GC-MS methods were used to quantify the intracellular
      intermediates of tricarboxylic acid cycle, glycolysis, and pentose phosphate
      pathway and for the determination of isotopomer fractions of the respective
      metabolites. Mass isotopomer fractions were determined in a transient (13)C
      labeling experiment using (13)C-labeled glucose as substrate. The absolute
      amounts of intracellular metabolites were obtained from a non-labeled experiment
      carried out in exactly the same way as the (13)C-labeling experiment, except that
      the media contained naturally labeled glucose only. Estimation of intracellular
      metabolic fluxes from the presented data is addressed in part II of this
      contribution.

PMID- 18095338
TI  - Weak attractive ligand-polymer and related interactions in catalysis and
      reactivity: impact, applications, and modeling.
AB  - The notion of weak attractive ligand-polymer interactions is introduced, and its
      potential application, importance, and conceptual links with "cooperative" ligand
      substrate interactions are discussed. Synthetic models of weak attractive ligand
      polymer interactions are described, in which intramolecular weak C-H...F-C
      interactions (the existence of which remains contentious) have been detected by
      NMR spectroscopy and neutron and X-ray diffraction experiments. These C-H...F-C
      interactions carry important implications for the design of catalysts for olefin
      polymerization, because they provide support for the practical feasibility of
      ortho-F...H(beta) ligand-polymer contacts proposed for living Group 4 fluorinated
      phenoxyimine catalysts. The notion of weak attractive noncovalent interactions
      between an "active" ligand and the growing polymer chain is a novel concept in
      polyolefin catalysis.

PMID- 18095340
TI  - Transcription factor onecut3 regulates intrahepatic biliary development in
      zebrafish.
AB  - Members of the onecut family of transcription factors play important roles in the
      development of the liver and pancreas. We have shown previously that onecut1
      (hnf6) is important during the terminal stages of intrahepatic biliary
      development in zebrafish. Here we report the characterization of a third
      zebrafish onecut gene, onecut3 (oc3), and assay its expression during development
      and its role in biliary duct formation using morpholino antisense oligonucleotide
      mediated knockdown. These experiments reveal an important role for oc3 during the
      earliest stages of zebrafish biliary development, and suggest that zebrafish oc3
      is the functional ortholog of mammalian hnf6, a gene that directs biliary
      differentiation from bipotential progenitor cells. Consistent with this,
      zebrafish hnf6 expression was significantly reduced in oc3-deficient larvae.
      Knockdown of hnf6 in wild-type zebrafish larvae also significantly reduced oc3
      expression, suggesting a complex interaction between onecut family member
      proteins during the latter stages of zebrafish biliary development.

PMID- 18095341
TI  - Six cadm/SynCAM genes are expressed in the nervous system of developing
      zebrafish.
AB  - The Cadm (cell adhesion molecule) family of cell adhesion molecules (also known
      as IGSF4, SynCAM, Necl and TSLC) has been implicated in a multitude of
      physiological and pathological processes, such as spermatogenesis, synapse
      formation and lung cancer. The precise mechanisms by which these adhesion
      molecules mediate these diverse functions remain unknown. To investigate
      mechanisms of action of these molecules during development, we have identified
      zebrafish orthologs of Cadm family members and have examined their expression
      patterns during development and in the adult. Zebrafish possess six cadm genes.
      Sequence comparisons and phylogenetic analysis suggest that four of the zebrafish
      cadm genes represent duplicates of two tetrapod Cadm genes, whereas the other two
      cadm genes are single orthologs of tetrapod Cadm genes. All six zebrafish cadms
      are expressed throughout the nervous system both during development and in the
      adult. The spatial and temporal patterns of expression suggest multiple roles for
      Cadms during nervous system development.

PMID- 18095344
TI  - Head involution in Drosophila: genetic and morphogenetic connections to dorsal
      closure.
AB  - Dorsal closure and head involution are complex morphogenetic processes that occur
      nearly simultaneously, midway through Drosophila embryonic development. While
      dorsal closure has been studied extensively in terms of both its morphology and
      genetics, head involution has not been described comprehensively. A thorough
      review of the literature nonetheless reveals considerable information regarding
      the genetic components of head involution. In several instances, authors have
      made explicit references to head involution in regard to mutant phenotypes; in
      others, we have made this connection. Here we collect, catalogue, and discuss
      published head involution studies. In considering and integrating the data, an
      enhanced appreciation of the molecular mechanisms underlying head involution and
      its molecular kinship with dorsal closure has emerged.

PMID- 18095342
TI  - TGF-beta signaling is dynamically regulated during the alveolarization of rodent
      and human lungs.
AB  - Although transforming growth factor-beta (TGF-beta) signaling negatively
      regulates branching morphogenesis in early lung development, few studies to date
      have addressed the role of this family of growth factors during late lung
      development. We describe here that the expression, tissue localization, and
      activity of components of the TGF-beta signaling machinery are dynamically
      regulated during late lung development in the mouse and human. Pronounced changes
      in the expression and localization of the TGF-beta receptors Acvrl1, Tgfbr1,
      Tgfbr2, Tgfbr3, and endoglin, and the intracellular messengers Smad2, Smad3,
      Smad4, Smad6, and Smad7 were noted as mouse and human lungs progressed through
      the canalicular, saccular, and alveolar stages of development. TGF-beta
      signaling, assessed by phosphorylation of Smad2, was detected in the vascular and
      airway smooth muscle, as well as the alveolar and airway epithelium throughout
      late lung development. These data suggest that active TGF-beta signaling is
      required for normal late lung development.

PMID- 18095345
TI  - Sexual dimorphic expression of DMRT1 and Sox9a during gonadal differentiation and
      hormone-induced sex reversal in the teleost fish Nile tilapia (Oreochromis
      niloticus).
AB  - We examined the expression profiles of tDMRT1 and Sox9a during gonadal sex
      differentiation and hormone-induced sex reversal. tDMRT1 was detected in the
      gonial germ-cell-surrounding cells in XY fry specifically before the appearance
      of any signs of morphological sex differentiation, that is, sex differences in
      germ cell number and histogenesis, such as differentiation into intratesticular
      efferent duct or ovarian cavity. The signals became localized in the Sertoli and
      epithelial cells comprising the efferent duct during gonadal differentiation.
      After the induction of XY sex reversal with estrogen, tDMRT1 decreased and then
      disappeared completely. In contrast, tDMRT1 was expressed in the germ-cell
      surrounding cells in XX sex reversal with androgen. On the other hand, Sox9a did
      not show sexual dimorphism before the appearance of sex differences in
      histogenesis and was not expressed in the efferent duct in the testis. These
      results suggest that tDMRT1 is a superior testicular differentiation marker in
      tilapia.

PMID- 18095346
TI  - Evaluation of evidence for infection as a mode of action for induction of rat
      lymphoma.
AB  - The European Food Safety Authority (EFSA) released a 2006 report questioning the
      relationship of aspartame exposure with increased incidence of
      lymphomas/leukemias in a European Ramazzini Foundation (ERF) rat study. The EFSA
      report suggested that the lymphoma/leukemia findings were most likely explained
      by infection in the rat colony. The ERF has also conducted the only available
      long-term oral study of methyl tertiary-butyl ether (MTBE). Thus, using the EFSA
      report as support, some have now raised questions about the human relevance of
      MTBE-associated hemolymphoreticular tumors reported by the ERF in female rats as
      well as whether their incidence was elevated above background levels. In this
      report, we discuss the hypothesized mode of action (MOA) of infection-induced
      lymphoma and its relevance to MTBE-associated lymphomas. We address the
      relationship of rat strain and study duration to lymphoma susceptibility and
      review evidence of low background rates of this tumor in control animals at the
      ERF, similar survival rates for female rats at the ERF and National Toxicology
      Program (NTP), and chemical- and gender-specificity of tumor induction for this
      type of tumor in studies at the ERF. We find that the background incidence of
      hemolymphoreticular tumors in female rats in the MTBE study is consistent with
      contemporaneous studies at the ERF and that there is an exposure-related effect,
      which is unlikely to be due to infections. We examine more recent tumor
      classification schemes for lymphomas, which support the combination of
      lymphoblastic leukemias and lymphomas reported by Belpoggi et al. ([1995] Toxicol
      Ind Health 11:119-149; [1998] Eur J Oncol 3:201-206).

PMID- 18095347
TI  - Cloning and functional characterization of two key enzymes of glycosphingolipid
      biosynthesis in the amphibian Xenopus laevis.
AB  - Gangliosides are a subfamily of complex glycosphingolipids (GSLs) with important
      roles in many biological processes. In this study, we report the cDNA cloning,
      functional characterization, and the spatial and temporal expression of Xlcgt and
      Xlgd3 synthase during Xenopus laevis development. Xlcgt was expressed both
      maternally and zigotically persisting at least until stage 35. Maternal Xlgd3
      synthase mRNA could not be detected and showed a steady-state expression from
      gastrula to late tailbud stage. Xlcgt is mainly present in involuted paraxial
      mesoderm, neural folds, and their derivatives. Xlgd3 synthase transcripts were
      detected in the dorsal blastoporal lip, in the presumptive neuroectoderm, and
      later in the head region, branchial arches, otic and optic primordia. We
      determined the effect of glycosphingolipid depletion with 1-phenyl-2-palmitoyl-3
      morpholino-1-propanol (PPMP) in mesodermal layer. PPMP-injected embryos showed
      altered expression domains in the mesodermal markers. Our results suggest that
      GSL are involved in convergent-extension movements during early development in
      Xenopus.

PMID- 18095348
TI  - Emilin genes are duplicated and dynamically expressed during zebrafish embryonic
      development.
AB  - Emilins are a family of extracellular matrix proteins with common structural
      organization and containing a characteristic N-terminal cysteine-rich domain. The
      prototype of this family, Emilin-1, is found in human and murine organs in
      association with elastic fibers, and other emilins were recently isolated in
      mammals. To gain insight into these proteins in lower vertebrates, we
      investigated the expression of emilins in the fish Danio rerio. Using sequence
      similarity tools, we identified eight members of this family in zebrafish. Each
      emilin gene has two paralogs in zebrafish, showing conserved structure with the
      human ortholog. In situ hybridization revealed that expression of zebrafish
      emilin genes is regulated in a spatiotemporal manner during embryonic
      development, with overlapping and site-specific patterns mostly including
      mesenchymal structures. Expression of certain emilin genes in peculiar areas,
      such as the central nervous system or the posterior notochord, suggests that they
      may play a role in key morphogenetic processes.

PMID- 18095349
TI  - Genes of Hippo signaling network act unconventionally in the control of germline
      proliferation in Drosophila.
AB  - Hippo pathway and its related genes are required for growth control in various
      somatic tissues. The mutations of Hippo pathway components lead to tissue
      overgrowth cell-autonomously. Surprisingly, when we generated germline mutant
      clones of Hippo-network genes such as fat, expanded, hippo, salvador, and warts,
      we did not observe any overgrowth of these mutant cells. Consistently,
      overexpression of the progrowth gene yorkie, which is normally inhibited by Hippo
      signaling, did not lead to germline overgrowth either. In contrast to previous
      studies in epithelial tissues, these tumor suppressor genes are dispensable in
      germline cells for their proliferation control. Furthermore, we demonstrate that
      expanded functions nonautonomously to regulate spermatogonial proliferation. It
      appears that expanded acts from the somatic support cells surrounding the
      germline to restrict spermatogonial amplification.

PMID- 18095350
TI  - Polysialyltransferase expression is linked to neuronal migration in the
      developing and adult zebrafish.
AB  - Modulation of cell-cell adhesion is crucial for regulating neuronal migration and
      maintenance of structural plasticity in the embryonic and mature brain. Such
      modulation can be obtained by the enzymatic attachment of polysialic acid (PSA)
      to the neural cell adhesion molecule (NCAM) by means of the
      polysialyltransferases STX and PST. Thus, differential expression of STX and PST
      is likely to be responsible for varying functions of PSA-NCAM during neuronal
      differentiation, maintenance, plasticity, and regeneration. We have isolated the
      zebrafish homologues of STX (St8sia2) and PST (St8sia4) and demonstrate that
      their expression in the embryonic and adult nervous system is often confined to
      regions of neuronal migration. Moreover, in the adult cerebellum, the
      complementary expression pattern of both polysialyltransferases suggests a
      function in regulating cerebellar neuronal plasticity. Enzymatic removal of PSA
      in the embryonic cerebellum results in impaired neuronal migration, suggesting
      that PSA-NCAM is a key regulator of motility for cerebellar neuronal progenitors.

PMID- 18095352
TI  - Developmental regulation of muscleblind-like (MBNL) gene expression in the
      chicken embryo retina.
AB  - Muscleblind-like (MBNL) is a CCCH zinc finger-containing RNA-binding protein
      required for the development of both muscle and photoreceptors in Drosophila; it
      is conserved evolutionarily, and it is associated in humans with the muscular
      disease myotonic dystrophy. Its role in the development of vertebrate retinal
      cells, however, remains unknown. As an initial approach to its investigation, we
      have cloned three chick muscleblind genes, characterized their isoforms, and
      examined their expression patterns in the chick embryo retina. The relative
      levels of expression of the MBNL genes increased during embryonic development. In
      situ hybridization (ISH) showed that the three MBNL mRNAs had widespread patterns
      of expression at all the developmental stages examined. Of interest, the temporal
      and spatial patterns of protein expression, detected by immunocytochemistry with
      antibodies against MBNL1 and MBNL2, were much more restricted than those seen by
      ISH. At early stages (ED5-7), for example, MBNL1 and MBNL2 mRNAs were present
      throughout the retina, but immunoreactivity for the corresponding proteins was
      largely restricted to the periphery of the optic cup (presumptive iris/ciliary
      epithelium/ciliary margin zone). MBNL1 and MBNL2 immunoreactivity became
      detectable at the fundus at later stages, but was limited to a very small subset
      of the cells that had ISH signals for the cognate mRNAs (particularly ganglion
      cells and photoreceptors). Within photoreceptors, MBNL1 and MBNL2
      immunoreactivity first appeared in their inner segments; MBNL2 remained there,
      but MBNL1 became subsequently localized to their synaptic terminals. These
      expression patterns are consistent with the possibility that MBNLs may regulate
      photoreceptor development in the chick retina, much as MBL does in Drosophila,
      and suggest that the expression of MBNL1 and MBNL2 may be regulated
      posttranscriptionally.

PMID- 18095354
TI  - Characterisation of the plasma membrane subproteome of bloodstream form
      Trypanosoma brucei.
AB  - Proteome analysis by conventional approaches is biased against hydrophobic
      membrane proteins, many of which are also of low abundance. We have isolated
      plasma membrane sheets from bloodstream forms of Trypanosoma brucei by
      subcellular fractionation, and then applied a battery of complementary protein
      separation and identification techniques to identify a large number of proteins
      in this fraction. The results of these analyses have been combined to generate a
      subproteome for the pellicular plasma membrane of bloodstream forms of T. brucei
      as well as a separate subproteome for the pellicular cytoskeleton. In parallel,
      we have used in silico approaches to predict the relative abundance of proteins
      potentially expressed by bloodstream form trypanosomes, and to identify likely
      polytopic membrane proteins, providing quality control for the experimentally
      defined plasma membrane subproteome. We show that the application of multiple
      high-resolution proteomic techniques to an enriched organelle fraction is a
      valuable approach for the characterisation of relatively intractable membrane
      proteomes. We present here the most complete analysis of a protozoan plasma
      membrane proteome to date and show the presence of a large number of integral
      membrane proteins, including 11 nucleoside/nucleobase transporters, 15 ion pumps
      and channels and a large number of adenylate cyclases hitherto listed as putative
      proteins.

PMID- 18095355
TI  - Proteomic analysis of bovine conceptus fluids during early pregnancy.
AB  - A proteomic analysis of bovine amniotic and allantoic fluids collected around Day
      45 of gestation was performed using gel-based and LC-based MS workflows. A
      depletion/enrichment protocol using ultrafiltration under denaturing and reducing
      conditions produced an enriched fraction containing protein species predominantly
      between 5 and 50 kDa molecular weight. The analyses of conceptus fluid proteins
      were performed using two strategies; first, 2-DE coupled with MALDI-TOF-MS/MS and
      LC-ESI-MS/MS analysis of individual protein spots and second, a global protein
      snapshot of the enriched 5-50 kDa protein fraction by LC-ESI-MS/MS and LC-MALDI
      TOF-MS/MS. Allocation of bovine specific protein identities was achieved by
      searching the Interactive Bovine In Silico SNP (IBISS) and NCBInr protein
      sequence databases resulting in the confident PMF identification and MS/MS
      confirmation of >200 2-DE generated allantoic fluids protein spots (74 individual
      protein species identified) and the MS/MS peptide identification of 105 LC-ESI
      MS/MS generated protein identities. In total, the identity of 139 individual
      protein species from allantoic fluids was confirmed with peptide sequence
      probability MOWSE scores at the p<0.05 level or better. The comparison of bovine
      Day 45 amniotic and allantoic fluids protein profiles revealed differences
      between these two conceptus fluids in early pregnancy.

PMID- 18095356
TI  - Proteome analysis of matrix vesicles isolated from femurs of chicken embryo.
AB  - Matrix vesicles (MVs) are extracellular organelles that initiate mineral
      formation, accumulating inorganic phosphate (P(i)) and calcium leading to the
      formation of hydroxyapatite (HA) crystals, the main mineral component of bones.
      MVs are produced during bone formation, as well as during the endochondral
      calcification of cartilage. MVs are released into the extracellular matrix from
      osseous cells such as osteoblasts and hypertrophic chondrocytes. In this report,
      using 1-D SDS-PAGE, in-gel tryptic digestion and an LC-MS-MS/MS protein
      identification protocol, we characterized the proteome of MVs isolated from
      chicken embryo (Gallus gallus) bones and cartilage. We identified 126 gene
      products, including proteins related to the extracellular matrix and ion
      transport, as well as enzymes, cytoskeletal, and regulatory proteins. Among the
      proteins recognized for the first time in MVs were aquaporin 1, annexin A1
      (AnxA1), AnxA11, glycoprotein HT7, G(i) protein alpha2, and scavenger receptor
      type B. The pathways for targeting the identified proteins into MVs and their
      particular functions in the biomineralization process are discussed. Obtaining a
      knowledge of the functions and roles of these proteins during embryonic
      mineralization is a prerequisite for the overall understanding of the initial
      mineral formation mechanisms.

PMID- 18095357
TI  - Urine protein profile of IgA nephropathy patients may predict the response to ACE
      inhibitor therapy.
AB  - This study was aimed at the search of urinary biomarkers which might help to
      predict the clinical response of IgA nephropathy (IgAN) patients to angiotensin
      converting enzyme inhibitors (ACEi). First, we studied the urinary proteome of 18
      IgAN patients (toward 20 healthy controls) who had been chronically treated with
      ACEi by using 2-D PAGE coupled to nano-HPLC-ESI-MS/MS analysis. We identified 3
      proteins, kininogen (p = 0.02), inter-alpha-trypsin-inhibitor heavy chain 4 (35
      kDa fragment) (p = 0.02) and transthyretin (p<0.0001), whose urinary excretion
      was different in IgAN patients' responders when compared to those who had not
      responded to ACEi. A reduction of daily proteinuria >50% and a stable renal
      function over time were used to classify patients as responders. Then, we adopted
      immunoblotting to confirm the predictive power of one of the above proteins,
      kininogen, in 20 patients with biopsy-proven IgAN, before starting any therapy.
      Thus, we confirmed that very low levels of kininogen urine excretion were indeed
      predictive of an inadequate or absent clinical response to ACEi therapy of IgAN
      patients, after 6-month follow-up. Concluding, the analysis of urine proteome of
      IgAN patients generated a set of proteins which distinguished subjects responsive
      to ACEi from those unresponsive to the inhibition of renin-angiotensin system
      (RAS).

PMID- 18095358
TI  - Proteomic profiling using mass spectrometry--does normalising by total ion
      current potentially mask some biological differences?
AB  - Normalisation of data to minimise the impact of technical variation on
      comparative sample analysis is often carried out. Using SELDI data as a model, we
      have examined the effects of normalisation by TIC which is commonly used for MS
      data. Significant intergroup differences in normalisation factor were found for
      serum profiles which could not be explained by experimental factors, implying
      that normalisation by TIC may in some situations also normalise biological
      differences and should be systematically evaluated.

PMID- 18095361
TI  - Post alignment clustering procedure for comparative quantitative proteomics LC-MS
      data.
AB  - Comparative LC-MS is a powerful method for detailed quantitative comparison of
      complex protein mixtures. Dedicated software is required for detection, matching,
      and alignment of peaks in multiple LC-MS datasets. However, retention time
      shifts, saturation effects, limitations of experimental accuracy, and possible
      occurrence of split peaks make it difficult for software to perfectly match all
      chromatograms. We describe a procedure to assess the above problems and show that
      dataset quality can be enhanced with the aid of cluster analysis.

PMID- 18095362
TI  - Multidimensional chromatography: validation and efficient fishing for biomarkers
      and fractions containing them using the VisualCockpit software package.
AB  - 2-D native LC yields thousands of fractions especially when applied to sera of
      different origin. Checking reproducibility of repeated separation of the same
      serum or searching for biomarker candidates and fractions containing them
      requires finding, selection, and comparison of interesting data subsets out of
      huge data volumes. An innovative software package is applied that markedly
      enhances simplicity, velocity, and reliability of (i) check of reproducibility of
      the separation method and (ii) analysis of proteomes pertaining to different
      disease states.

PMID- 18095363
TI  - Wiley-VCH and HUPO: a global effort to advance proteomic science.

PMID- 18095364
TI  - Protein Information Crawler (PIC): extensive spidering of multiple protein
      information resources for large protein sets.
AB  - Proteomic studies often produce sets of hundreds of proteins. Bioinformatic
      information for these large protein sets must be collected from multiple online
      resources. Protein Information Crawler (PIC) automatically bulk-collects such
      data from multiple databases and prediction servers, based on National Center for
      Biotechnology Information (NCBI) gi numbers or accession numbers, and summarizes
      them in a Microsoft Excel spreadsheet and/or HTML table. PIC greatly accelerates
      information procurement, helps to build customized protein information databases
      and drastically reduces manual database investigation in extensive proteomic
      studies. AVAILABILITY: http://www.zoo.uni-heidelberg.de/mfa/PIC.

PMID- 18095365
TI  - Transcriptome and proteome profiling of colon mucosa from quercetin fed F344 rats
      point to tumor preventive mechanisms, increased mitochondrial fatty acid
      degradation and decreased glycolysis.
AB  - Quercetin has been shown to act as an anticarcinogen in experimental colorectal
      cancer (CRC). The aim of the present study was to characterize transcriptome and
      proteome changes occurring in the distal colon mucosa of rats supplemented with
      10 g quercetin/kg diet for 11 wk. Transcriptome data analyzed with Gene Set
      Enrichment Analysis showed that quercetin significantly downregulated the
      potentially oncogenic mitogen-activated protein kinase (Mapk) pathway. In
      addition, quercetin enhanced expression of tumor suppressor genes, including
      Pten, Tp53, and Msh2, and of cell cycle inhibitors, including Mutyh. Furthermore,
      dietary quercetin enhanced genes involved in phase I and II metabolism, including
      Fmo5, Ephx1, Ephx2, and Gpx2. Quercetin increased PPARalpha target genes, and
      concomitantly enhanced expression of genes involved in mitochondrial fatty acid
      (FA) degradation. Proteomics performed in the same samples revealed 33 affected
      proteins, of which four glycolysis enzymes and three heat shock proteins were
      decreased. A proteome-transcriptome comparison showed a low correlation, but both
      pointed out toward altered energy metabolism. In conclusion, transcriptomics
      combined with proteomics showed that dietary quercetin evoked changes contrary to
      those found in colorectal carcinogenesis. These tumor-protective mechanisms were
      associated with a shift in energy production pathways, pointing at decreased
      cytoplasmic glycolysis and toward increased mitochondrial FA degradation.

PMID- 18095366
TI  - The effect of serum withdrawal on the protein profile of quiescent human dermal
      fibroblasts in primary cell culture.
AB  - The effect of serum deprivation on proliferating cells is well known, in contrast
      its role on primary cell cultures, at confluence, has not been deeply
      investigated. Therefore, in order to explore the response of quiescent cells to
      serum deprivation, ubiquitous mesenchymal cells, as normal human dermal
      fibroblasts, were grown, for 48 h after confluence, in the presence or absence of
      10% FBS. Fibroblast behaviour (i.e. cell morphology, cell viability, ROS
      production and elastin synthesis) was evaluated morphologically and
      biochemically. Moreover, the protein profile was investigated by 2-DE and
      differentially expressed proteins were identified by MS. Serum withdrawal caused
      cell shrinkage but did not significantly modify the total cell number. ROS
      production, as evaluated by the dihydroethidium (DH2) probe, was increased after
      serum deprivation, whereas elastin synthesis, measured by a colorimetric method,
      was markedly reduced in the absence of serum. By proteome analysis, 41 proteins
      appeared to significantly change their expression, the great majority of protein
      changes were related to the cytoskeleton, the stress response and the glycolytic
      pathway. Data indicate that human dermal fibroblasts in primary cell culture can
      adapt themselves to environmental changes, without significantly altering cell
      viability, at least after a few days of treatment, even though serum withdrawal
      represents a stress condition capable to increase ROS production, to influence
      cell metabolism and to interfere with cell behaviour, favouring the expression of
      several age-related features.

PMID- 18095367
TI  - Frontiers in glycomics: bioinformatics and biomarkers in disease. An NIH white
      paper prepared from discussions by the focus groups at a workshop on the NIH
      campus, Bethesda MD (September 11-13, 2006).
AB  - Key issues relating to glycomics research were discussed after the workshop
      entitled "Frontiers in Glycomics: Bioinformatics and Biomarkers in Disease" by
      two focus groups nominated by the organizers. The groups focused on two themes:
      (i) glycomics as the new frontier for the discovery of biomarkers of disease and
      (ii) requirements for the development of informatics for glycomics and
      glycobiology. The mandate of the focus groups was to build consensus on these
      issues and develop a summary of findings and recommendations for presentation to
      the NIH and the greater scientific community. A list of scientific priorities was
      developed, presented, and discussed at the workshops. Additional suggestions were
      solicited from workshop participants and collected using the workshop mailing
      list. The results are summarized in this White Paper, authored by the co-chairs
      of the focus groups.

PMID- 18095368
TI  - Cobaloxime-based photocatalytic devices for hydrogen production.

PMID- 18095369
TI  - Asymmetric Bronsted acid catalysis: enantioselective nucleophilic substitutions
      and 1,4-additions.

PMID- 18095370
TI  - Nanoporosity and exceptional negative thermal expansion in single-network cadmium
      cyanide.

PMID- 18095373
TI  - Identification of membrane-associated proteins from Campylobacter jejuni strains
      using complementary proteomics technologies.
AB  - Campylobacter jejuni is the leading cause of food- and water-borne illness world
      wide. The membrane-associated proteome of a recent C. jejuni gastrointestinal
      isolate (JHH1) was generated by sodium carbonate precipitation and
      ultracentrifugation followed by 2-DE and MALDI-TOF MS as well as 2-DLC (strong
      cation exchange followed by RP chromatography) of trypsin digests coupled to
      MS/MS (2-DLC/MS/MS). 2-DE/MS identified 77 proteins, 44 of which were predicted
      membrane proteins, while 2-DLC/MS/MS identified 432 proteins, of which 206 were
      predicted to be membrane associated. A total of 453 unique proteins (27.4% of the
      C. jejuni theoretical proteome), including 187 bona fide membrane proteins were
      identified in this study. Membrane proteins were also compared between C. jejuni
      JHH1 and ATCC 700297 to identify factors potentially associated with increased
      gastrointestinal virulence. We identified 28 proteins that were significantly
      (>two-fold) more abundant in, or unique to, JHH1, including eight proteins
      involved in chemotaxis signal transduction and flagellar motility, the amino acid
      binding surface antigens CjaA and CjaC, and four outer membrane proteins (OMPs)
      of unknown function (Cj0129c, Cj1031, Cj1279c, and Cj1721c). Immunoblotting using
      convalescent patient sera generated post-gastrointestinal infection revealed 13
      (JHH1) and 12 (ATCC 700297) immunoreactive proteins. These included flagellin
      (FlaA) and CadF as well as Omp18, Omp50, Cj1721c, PEB1A, PEB2, and PEB4A. This
      study provides a comprehensive analysis of membrane-associated proteins from C.
      jejuni.

PMID- 18095372
TI  - Use of 2-D DIGE analysis reveals altered phosphorylation in a tropomyosin mutant
      (Glu54Lys) linked to dilated cardiomyopathy.
AB  - Current electrophoretic methods have not been optimized to fully separate post
      translationally modified mutant forms of tropomyosin (Tm) from wild-type cardiac
      samples. We describe here a method employing a modified 2-D PAGE/2-D DIGE
      protocol, to fully separate native, mutant (E54K), and phosphorylated forms of
      Tm. Our data demonstrate the first evidence of a significant (approximately 40%)
      decrease in Tm phosphorylation in transgenic compared to non-transgenic mouse
      hearts, and indicate that altered phosphorylation may be a significant factor in
      the linkage of the E54K mutation to dilated cardiomyopathy.

PMID- 18095374
TI  - PlyC, a novel bacteriophage lysin for compartment-dependent proteomics of group A
      streptococci.
AB  - Streptococcus pyogenes (Spy) (group A streptococci) is an important and
      exclusively human bacterial pathogen, which uses secreted and surface-associated
      proteins to circumvent the innate host defense mechanisms and to adhere and
      internalize into host cells. Thus, investigation of the bacterial extracellular
      compartments, including secreted and cell wall-associated subproteomes, is
      crucial for understanding adherence, invasion, and internalization mechanisms as
      major steps of Spy pathogenesis. Here, we compared a bacteriophage encoded cell
      wall hydrolase, PlyC, a multimeric lysin of the C1 bacteriophage, with the
      established glycosidase, mutanolysin, from Streptomyces globisporus for their
      suitability to efficiently digest Spy cell walls and release cell wall-anchored
      Spy proteins for subsequent proteome research. Our results show that PlyC is
      superior for cell wall protein extraction compared to mutanolysin due to its
      higher activity and specificity as an N-acetylmuramoyl-L-alanine amidase.
      Furthermore, our experimental design allowed us to delineate the actual
      localization of the proteins despite contamination with intracellular proteins.

PMID- 18095375
TI  - Early manganese-toxicity response in Vigna unguiculata L.--a proteomic and
      transcriptomic study.
AB  - The apoplast is known to play a predominant role in the expression of manganese
      (Mn) toxicity in cowpea (Vigna unguiculata L.) leaves. To unravel early Mn
      toxicity responses after 1-3 days Mn treatment also in the leaf symplast, we
      studied the symplastic reactions induced by Mn in two cultivars differing in Mn
      tolerance on a total cellular level. Comparative proteome analyses of plants
      exposed to low or high Mn allowed to identify proteins specifically affected by
      Mn, particularly in the Mn-sensitive cowpea cultivar. These proteins are involved
      in CO(2) fixation, stabilization of the Mn cluster of the photosystem II,
      pathogenesis-response reactions and protein degradation. Chloroplastic proteins
      important for CO(2) fixation and photosynthesis were of lower abundance upon Mn
      stress suggesting scavenging of metabolic energy for a specific stress response.
      Transcriptome analyses supported these findings, but additionally revealed an
      upregulation of genes involved in signal transduction only in the Mn-sensitive
      cultivar. In conclusion, a coordinated interplay of apoplastic and symplastic
      reactions seems to be important during the Mn-stress response in cowpea.

PMID- 18095383
TI  - Mass spectrometry of hydantoin-derived selective androgen receptor modulators.
AB  - N-Aryl-hydroxybicyclohydantoins represent a new class of tissue-selective
      anabolic agents [selective androgen receptor modulators (SARMs)] and are
      promising therapeutics as well as drugs prohibited in amateur and professional
      sport. The dissociation behavior after negative and positive electrospray
      ionization (ESI) and subsequent collision-induced dissociation (CID) was studied
      with a drug candidate (BMS 564929) as well as structurally related and isotope
      labeled analogs using high resolution/high accuracy orbitrap mass spectrometry.
      Positive ionization and CID yielded characteristic product ions resulting from
      the cleavage of the hydantoin structure providing information about the proline
      derived nucleus as well as the substituted aryl residue at m/z 96 and 193,
      respectively. Negative ESI and CID (MS/MS) yielded product ions mainly
      representing losses of water and CO(2), the latter of which is of particular
      significance as the hydantoin structure does not contain a carboxyl function.
      Employing MS(n) experiments with accurate mass determination on six model SARMs,
      dissociation pathways to characteristic product ions were proposed supporting the
      identification of these drugs, their metabolites or related compounds in future
      doping control assays.

PMID- 18095376
TI  - CTLA-4 disrupts ZAP70 microcluster formation with reduced T cell/APC dwell times
      and calcium mobilization.
AB  - CTLA-4 is a co-receptor that modulates the threshold of T cell activation and
      autoimmunity. We previously showed that CTLA-4 reverses the TCR-mediated stop
      signal needed for T cell/APC interactions [Schneider et al., Science 2006, 313:
      1972]. In this study, using a different T cell system, we show that CTLA-4
      expression changed the behavior of T8.1 T cells by reducing the contact time
      between T cell and APC, preventing re-inforced contacts, and reducing the contact
      area at the immunological synapse. This led to a major reduction in Ca(2+)
      influx/mobilization and interleukin-2 production. Further, anti-CD3/CTLA-4
      increased T cell motility on antibody-coated glass slides, concurrent with an
      abrogation of ZAP70 microcluster formation. Our findings further support a role
      for CTLA-4 in limiting the interaction between T cell and APC that is needed for
      optimal activation.

PMID- 18095384
TI  - Assessing the risk of resistance in Pseudoperonospora cubensis to the fungicide
      flumorph in vitro.
AB  - BACKGROUND: The oomycete fungicide flumorph is a recently introduced carboxylic
      acid amide (CAA) fungicide. In order to evaluate the risk of developing field
      resistance to flumorph, the authors compared it with dimethomorph and
      azoxystrobin with respect to the ease of obtaining resistant isolates to these
      fungicides, the level of resistance and their fitness in the laboratory. RESULTS:
      Mutants with a high level of resistance to azoxystrobin were isolated readily by
      adaptation and UV irradiation, and their fitness was as good as that of the
      parent isolates. Attempts to generate mutants of Pseudoperonospora cubensis
      (Burk. & MA Curtis) Rostovsev resistant to flumorph and dimethomorph by sporangia
      adaptation on fungicide-treated leaves were unsuccessful. However, moderately
      resistant mutants were isolated using UV mutagenesis, but their resistance level
      [maximum resistance factor (MRF) < 100] was much lower than that of the
      azoxystrobin-resistant mutant (MRF = 733). With the exception of stability of
      resistance, all mutants showed low pathogenicity and sporulation compared with
      wild-type isolates and azoxystrobin-resistant mutants. There is cross-resistance
      between flumorph and dimethomorph, suggesting that they have the same resistance
      mechanism. CONCLUSION: The above results suggest that the resistance risk of
      flumorph may be similar to that of dimethomorph but lower than that of
      azoxystrobin and can be classified as moderate. Thus, it can be managed by
      appropriate product use strategies.

PMID- 18095385
TI  - Insecticidal activity of menthol derivatives against mosquitoes.
AB  - BACKGROUND: The insecticidal activity of essential oil of Mentha piperita L.
      emend. Huds. against local mosquitoes as disease vectors was recognized and found
      to be due to the presence of menthol, which is the major aroma compound of the
      oil. The minor compounds of the oil, i.e. menthone, beta-caryophyllene, menthyl
      acetate, limonene, alpha-pinene and pulegone, showed either less or no activity
      against the mosquitoes tested. L-Menthol derivatives were synthesized and their
      knockdown effect and mortality were evaluated against local mosquitoes of Culex
      quinquefasciatus Say, Aedes aegypti L. and Anopheles tessellatus Theobald as
      disease vectors. This is the first report of mosquitocidal activity of menthol
      and its derivatives against Cx. quinquefasciatus, Ae. aegypti and An.
      tessellatus. RESULTS: Derivative synthesis followed by structure-activity
      relationship studies identified several derivatives, i.e. menthyl chloroacetate,
      menthyl dichloroacetate, menthyl cinnamate, menthone glyceryl acetal, thymol,
      alpha-terpineol and mugetanol, with enhanced mosquitocidal activity against Cx.
      quinquefasciatus, Ae. aegypti and An. tessellatus relative to the parent compound
      L-menthone. CONCLUSION: In ester derivatives of L-menthol the optimum activity is
      dependent on the size and shape of the ester group and the presence of chlorine
      atoms in the ester group. In structurally related derivatives of L-menthol the
      optimum activity is dependent on the aromaticity, the degree of unsaturation, the
      position of the hydroxy group and the type of functional group.

PMID- 18095386
TI  - UV laser-induced desorption mechanism analyzed through two-layer alkali halide
      samples.
AB  - Time of flight-mass spectrometry (TOF-MS) is used to analyze positive and
      negative desorbed ions generated by UV laser ablation of several alkali (X)
      halide (Y) salts. Most of the observed desorbed cluster ions have the structure
      (XY)(n)X(+) or (XY)(n)Y(-). Their desorption yields decrease as exp(-kn), where k
      approximately 2 for both series, suggesting that the neutral component (XY)(n)
      plays the dominant role in the desorption process. Mass spectrum measurements
      were performed for compound samples in which two salts (out of CsI, RbI, KBr, KCl
      and KI) are homogeneously mixed or disposed in two superposed layers. The
      detection of small new ion species and large cluster ions of the original salts
      supports the scenario that the uppermost layers are completely atomized while
      deep layers are emitted colder and fragmented: It is proposed that ns-pulsed
      laser induced desorption of ionic salts occurs via two sequential mechanisms: (1)
      ejection of cations and anions in the hot plume, followed by recombination into
      new cluster ions and (2) ejection of relatively cold preformed species originated
      from deep layers or from periphery of the irradiated region.

PMID- 18095388
TI  - Stress responses in biology and medicine. Proceedings of the 2nd World Conference
      on Stress, August 23-26, 2007, Budapest, Hungary.

PMID- 18095387
TI  - Questions updated euthanasia guidelines.

PMID- 18095389
TI  - Daptomycin.
AB  - Severe gram-positive infections: no advantage, but risk of muscle disorders.

PMID- 18095390
TI  - Glatiramer: cutaneous necrosis.

PMID- 18095391
TI  - Diabetes prevention: still no effective drugs.
AB  - In the DREAM trial, involving more than 5000 patients with "impaired glucose
      tolerance", ramipril had no preventive effect, while rosiglitazone had cardiac
      adverse effects.

PMID- 18095393
TI  - Discipline decisions and promoting safe practice.

PMID- 18095394
TI  - YAAP: yet another adaptive procedure.
AB  - YAAP is an implementation of an adaptive psychophysical method, based on Bayesian
      statistics, for estimating the threshold of a psychometric function. On the basis
      of Bayesian probability intervals, a dynamic termination criterion allows for
      threshold estimation within pre-specified confidence limits.

PMID- 18095395
TI  - Bootstrap estimates of the statistical accuracy of thresholds obtained from
      psychometric functions.
AB  - Estimates of the accuracy of a threshold obtained from a psychometric function
      are often based on asymptotic theory. When the number of trails is small,
      however, these estimates may be untrustworthy. A computer program is described
      that uses a move reliable bootstrap approach to obtaining estimates of the
      standard deviation and confidence limits of a threshold and of the slope and
      spread of the psychometric function for any criterion level of performance.

PMID- 18095396
TI  - d'plus: A program to calculate accuracy and bias measures from detection and
      discrimination data.
AB  - The program d'plus calculates accuracy (sensitivity) and response-bias parameters
      using Signal Detection Theory. Choice Theory, and 'nonparametric' models. is is
      appropriate for data from one-interval, two- and three-interval forced-choice,
      same different, ABX, and oddity experimental paradigms.

PMID- 18095397
TI  - Establishing and implementing the essential nursing competencies and curricula
      guidelines for genetics and genomics.

PMID- 18095398
TI  - Desperately seeking new graduates with specialized expertise.

PMID- 18095399
TI  - Fighting foot-and-mouth disease in Mexico: popular protest against diplomatic
      decisions.

PMID- 18095400
TI  - The Oslers and the College of Physicians of Philadelphia.

PMID- 18095401
TI  - At the heart of a new profession: Margaret Stansfeld, a radical English
      educationalist.
AB  - It is argued here that Margaret Stansfeld, as Principal of Bedford Physical
      Training College from 1903 to 1945, succeeded in developing a strong and
      distinctive 'female tradition' which was widely disseminated by her students. She
      was realistic in recognizing the strength of opposition from a male-dominated
      society to women's participation in sport and physical exercise, and steadily
      overcame it. She achieved this partly by insisting on acceptably 'ladylike'
      behaviour from her students in conventional social situations, and also by
      bringing the work of the college into the public arena, through displays of
      gymnastics, through the use of elementary schools for part of the student
      teaching experience, through the running of a physiotherapy clinic where
      treatment was given free of charge, and through the use of students in the
      outpatients ward of the local hospital. Stansfeld herself was PE organizer for
      Bedford from 1923. But she was not afraid to fight against prejudice which was
      demonstrably based on false premises, e.g. medical opposition to women taking
      part in strenuous physical exercise, or to insist on appropriate clothing for
      women, however indecorous some might have considered it. The college's long-term
      success resulted from a series of factors: its curriculum and ethos, the
      networking process it fostered, the quality of the teachers it produced, the
      strength of the Old Students' Association, Stansfeld's willingness to embrace new
      ideas, and the growing academic respectability of the subject. The pivot of the
      whole process was Stansfeld herself - autocratic, austere, but an inspirational
      teacher - feared and loved. Students who succeeded were empowered - 'She prepared
      us for LIFE!' The success of her Old Students was the most important feature,
      e.g. Phyllis Colson, originator and director of the Central Council of Physical
      Recreation. Hundreds of others, less well known, in schools all over Britain and
      abroad, gave their pupils pride in themselves, not only through the experience of
      games, gymnastics and dance, but through moral example - 'fair play' - and many
      brought the newest innovations into schools (e.g. Elizabeth Swallow was the first
      to introduce Laban into a maintained school in 1939). Stansfeld's indomitable
      spirit was always in evidence, even at the end of her life - she returned to the
      office of Principal in 1948 at age 88, three years before her own death, after
      the unexpected death of her successor. It was this strength of will and character
      above all else which empowered her students as women and as teachers, and which
      enabled them in their turn to empower their own pupils, and so to replace the
      myth that physical activities were damaging to women with the growing realization
      that sport and physical recreation are as beneficial to women as they are to men.
      Stansfeld was justifiably recognized in her time as a pioneer in the advancement
      of women's PE, e.g. by the McNair Report (1942), which argued that nothing
      comparable had been achieved for men. She was the last survivor of the
      originators of women's PE, and the most influential. It is ironic that the rise
      of feminism in the second half of the century coincided with the dissipation of
      the female tradition, epitomised by Stansfeld, as physical education for women,
      developed by women, in the first half of the century increasingly came to be
      controlled by men in the second half. It is perhaps the ultimate demonstration of
      the success of Stansfeld's work that, despite this, at the beginning of the
      twenty-first century women are free to participate in and enjoy sport and
      physical leisure in a way that would have seemed impossible at the beginning of
      the twentieth.

PMID- 18095402
TI  - Sudden cardiac death in athletes: rethinking "hypertropic cardiomyopathy".

PMID- 18095403
TI  - The book that Dr. Osler lost.

PMID- 18095404
TI  - The Linacre, Harvey, and Sydenham triptych.

PMID- 18095405
TI  - The literary works of Sir William Osler.
AB  - A paper read at the first regular meeting of the Osler Society of McGill
      University, October 19, 1921.

PMID- 18095406
TI  - Bibliography. Current world literature. Micronutrients.

PMID- 18095407
TI  - Bibliography. Current world literature. Functional foods.

PMID- 18095408
TI  - Saline or albumin for fluid resuscitation in traumatic brain injury.

PMID- 18095409
TI  - Women's choices under the law: marriage, divorce, and illicit sex in the Qing and
      the Republic.

PMID- 18095410
TI  - Books for the Bibliotheca: a study of Sir William Osler's book bills.

PMID- 18095411
TI  - Internet searches.

PMID- 18095412
TI  - Updating OSHA standards based on national consensus standards. Direct final rule.
AB  - In this direct final rule, the Agency is removing several references to consensus
      standards that have requirements that duplicate, or are comparable to, other OSHA
      rules; this action includes correcting a paragraph citation in one of these OSHA
      rules. The Agency also is removing a reference to American Welding Society
      standard A3.0-1969 ("Terms and Definitions") in its general-industry welding
      standards. This rulemaking is a continuation of OSHA's ongoing effort to update
      references to consensus and industry standards used throughout its rules.

PMID- 18095413
TI  - Narrative and poetry writing for professional development.
AB  - Narrative, metaphor and image are habitual forms of making sense of the world and
      can be powerfully harnessed for professional development. Writing is a particular
      form of expression and communication that allows practitioners to speedily
      identify and engage with their most sensitively critical aspects of practice, and
      forms the basis for critical, confidential, trusted discussion. This article
      gives underlying theories and dominant practices of reflective writing as a
      professional development activity.

PMID- 18095414
TI  - Sir William Osler and Mabel Purefoy Fitzgerald.

PMID- 18095415
TI  - The library of the Osler Club of London.

PMID- 18095416
TI  - Leonard Leopold Mackall (1879-1937), the anonymous fourth editor of the
      Bibliotheca.

PMID- 18095417
TI  - Protecting pet hospice.

PMID- 18095418
TI  - Osler Library fiftieth anniversary exhibition.

PMID- 18095419
TI  - The book-plate that never was.

PMID- 18095420
TI  - The Osler Library at fifty: the Library today.

PMID- 18095421
TI  - Fate of Escherichia coi O157:H7 during on-farm dairy manure-based composting.
AB  - Studies were conducted to determine the fate of Escherichia coli O157:H7 in dairy
      manure-based compost in a field setting. Two trials were performed involving
      duplicate compost heaps constructed at an outdoor fenced site. The compost heaps
      were composed of dairy manure, old hay, feed waste, a mixture of sawdust and calf
      feces, and fresh hay. Samples of the composting mixture were inoculated with stx
      negative E. coli O157:H7 B6914 at initial concentrations of 10(7) and 10(5) CFU/g
      for trial 1 and trial 2, respectively. Individual sample bags were placed on the
      surface and at three locations (top, center, and bottom) within each heap.
      Although the compost heaps achieved temperatures of 50 degrees C or above at all
      internal locations for at least 7 days, temperature stratification was observed.
      In trial 1, E. coli O157:H7 was detected by enrichment through 14 days within the
      heaps. When inoculated with 10(5) CFU/g in trial 2, E. coli O157:H7 was detected
      only through days 2, 2, and 5 at the top, center, and bottom locations,
      respectively. For both trials, the pathogen survived at the heap's surface for up
      to 4 months. The indicator commensal E. coli and coliforms were inactivated at a
      rate similar to that for E. coli O157:H7. Results indicate that composting, with
      periodic heap turning, can be a practical approach to inactivating E. coli
      O157:H7 in cattle wastes on the farm. Our data also suggest when compost heaps
      are not turned, E. coli O157:H7 may survive for months at the heap surface.

PMID- 18095422
TI  - Recirculating immunomagnetic separation and optimal enrichment conditions for
      enhanced detection and recovery of low levels of Escherichia coli O157:H7 from
      fresh leafy produce and surface water.
AB  - The objective of this study was to develop a rapid, simple method for enhanced
      detection and isolation of low levels of Escherichia coli O157:H7 from leafy
      produce and surface water using recirculating immunomagnetic separation (RIMS)
      coupled with real-time PCR and a standard culture method. The optimal enrichment
      conditions for the method also were determined. Analysis of real-time PCR data
      (C(T) values) suggested that incubation of lettuce and spinach leaves rather than
      rinsates provides better enrichment of E. coli O157:H7. Enrichment of lettuce or
      spinach leaves at 42 degrees C for 5 h provided better detection than enrichment
      at 37 degrees C. Extended incubation of surface water for 20 h at 42 degrees C
      did not improve the detection. The optimized enrichment conditions were also
      employed with modified Moore swabs, which were used to sample flowing water
      sites. Positive isolation rates and real-time PCR results indicated an increased
      recovery of E. coli O157:H7 from all samples following the application of RIMS.
      Under these conditions, the method provided detection and/or isolation of E. coli
      O157:H7 at levels as low as 0.07 CFU/g of lettuce, 0.1 CFU/g of spinach, 6
      CFU/100 ml of surface water, and 9 CFU per modified Moore swab. During a 6-month
      field study, modified Moore swabs yielded high isolation rates when deployed in
      natural watershed sites. The method used in this study was effective for
      monitoring E. coli O157:H7 in the farm environment, during postharvest
      processing, and in foodborne outbreak investigations.

PMID- 18095423
TI  - Persistence and growth of different Salmonella serovars on pre- and postharvest
      tomatoes.
AB  - The interaction of a range of Salmonella serovars with pre- and postharvest
      tomatoes was evaluated. Serovars were selected on the basis of previous
      association in tomato-linked outbreaks of salmonellosis (Salmonella Javiana,
      Salmonella Montevideo, and Salmonella Newport) or those typically isolated from
      animal or clinical infections (Salmonella Dublin, Salmonella Enteritidis,
      Salmonella Hadar, Salmonella Infantis, Salmonella Typhimurium, and Salmonella
      Senftenberg). Salmonella serovars introduced onto the flowers of growing plants
      were recovered on and within the developing tomato fruit. Of all the Salmonella
      serovars tested, Montevideo appeared to be more adapted to survival within
      tomatoes and was recovered from 90% of the fruit screened. All of the Salmonella
      serovars could persist and grow when introduced onto unripened (green) tomato
      fruit. In general, growth (internal and external) was promoted at the high
      incubation temperature (25 degrees C) and high relative humidity (95%), although
      this was serovar dependent. The growth and persistence of Salmonella introduced
      on and into ripened (red) tomatoes was serovar dependent. Salmonella serovars
      Enteritidis, Typhimurium, and Dublin were less adapted to grow in or on intact
      red tomatoes than were serovars Hadar, Montevideo, or Newport. The results
      illustrated that a diverse range of Salmonella serovars can become established
      within and/or on preharvest tomatoes. The majority of Salmonella can grow and
      become established both on and within unripened tomatoes, but growth on ripened
      fruit was serovar dependent. The results provide a possible explanation why only
      a narrow range of Salmonella serovars are associated with foodborne illness
      outbreaks linked to tomatoes.

PMID- 18095424
TI  - Using indicator bacteria and Salmonella test results from three large-scale beef
      abattoirs over an 18-month period to evaluate intervention system efficacy and
      plan carcass testing for Salmonella.
AB  - To develop a process for predicting the likelihood of Salmonella contamination on
      beef carcasses, we evaluated the influence of several possible causative factors
      (i.e., year, abattoir, day of week, month, and intervention system components) on
      the risk of Salmonella and indicator organism contamination. Hide and carcass
      sponge samples were collected in 2005 to 2006 in six steps at three abattoirs in
      the East (A), Midwest (B), and Southwest (C) United States. Each abattoir used
      the same intervention system. Samples were analyzed for aerobic plate counts
      (APCs; n = 18,990) and Enterobacteriaceae counts (EBCs; n = 18,989) and the
      presence or absence of Salmonella (n = 5,355). Our results demonstrated that many
      factors play a significant role in the level of microbial contamination of beef
      carcasses. Overall, Salmonella prevalence and EBC levels were significantly
      higher in 2006 than in 2005. APCs and EBCs were highest in abattoirs A (3.57 log
      CFU/100 cm2) and B (1.31 log CFU/100 cm2). The odds of detecting a positive
      Salmonella isolate were greatest in abattoir C and lowest in abattoir A. Across
      the three abattoirs, the overall intervention process effectively reduced
      microbiological contamination. Salmonella prevalence fell from 45%
      (preevisceration) to 0.47% (postchilled-lactic acid), and there were APC and EBC
      reductions of 5.43 and 5.28 log CFU/100 cm2, respectively, from hide-on to
      postchilled-lactic acid samples. At each abattoir, composites of three individual
      EBC-negative carcass samples yielded Salmonella-negative results 97 to 99% of the
      time. These results suggest the possibility of using indicator test results to
      accurately predict the absence of Salmonella in a beef carcass sample.

PMID- 18095425
TI  - Antimicrobial resistance and phage and molecular typing of Salmonella strains
      isolated from food for human consumption in Spain.
AB  - The aims of this study were to ascertain the population structure and
      antimicrobial susceptibility of Salmonella enterica serovars isolated in 2002
      from food in 16 Spanish regions. Serovars were characterized by serotyping, phage
      typing, antimicrobial susceptibility, and pulsed-field gel electrophoresis (PFGE)
      typing, and 264 nonrelated strains were selected for further analysis. The main
      sources were eggs and their derivatives (21.6% of strains), poultry and related
      products (16.6%), and seafood (16.3%). High serotype diversity was detected (51
      serotypes); the most common were Enteritidis (n = 96, 36.3%) and Typhimurium (n =
      53, 20.1%), followed by a miscellaneous group of 49 different serotypes (n = 115,
      43.5%). A 15% increase in Salmonella Enteritidis isolation was observed. Common
      phage types for Salmonella Enteritidis were PT1 (41.6% of isolates), PT4 (9.4%),
      PT6 (9.4%), and PT6a (9.4%), and common types for Salmonella Typhimurium were
      DTU302 (18.8%), DT104 (15.1%), and DT104B (13.2%). Salmonella Enteritidis strains
      were categorized into eight PFGE types with a similarity of 81 to 96%, and 73.9%
      of the strains were grouped into just one cluster. Salmonella Typhimurium
      isolates were divided into 13 PFGE types with a similarity of 64 to 86%, and one
      predominant clone contained 41.5% of the strains. Resistance rates for Salmonella
      Enteritidis, Salmonella Typhimurium, and the miscellaneous group were,
      respectively, 8.3, 69.8, and 13.9% for ampicillin, 3.1, 52.8, and 59% for
      streptomycin, 40.6, 22.6, and 10.4% for nalidixic acid, 15.6, 71.7, and 31.1% for
      tetracycline, 7.3, 18.8, and 9.5% for trimethoprim-sulfamethoxazole, 0, 50.9, and
      4.3% for chloramphenicol, and 6.2, 71.7, and 17.4% for multiple (at least four)
      antimicrobials. All the strains remained susceptible to other beta-lactams and
      fluoroquinolones. Surveillance of S. enterica isolated from food is strongly
      recommended to reduce community exposure to antimicrobial resistant strains.

PMID- 18095426
TI  - Effect of inhibitory extracts derived from liquid smoke combined with postprocess
      pasteurization for control of Listeria monocytogenes on ready-to-eat meats.
AB  - Surface pasteurization was examined in combination with low-phenolic
      antimicrobial extracts derived from liquid smoke to inhibit and prevent the
      growth of Listeria monocytogenes during the shelf life of ready-to-eat meats. In
      preliminary trials with retail frankfurters, one smoke derivative (2-min dip)
      produced a 0.3-log reduction of L. monocytogenes and a 1-min in-bag
      pasteurization (73.9 degrees C) produced a 2.9-log reduction, whereas a
      combination of the two treatments produced a 5.3-log reduction that resulted in
      no detectable Listeria by week 3 under accelerated shelf-life conditions (10
      degrees C). In trials with frankfurters manufactured without lactate or diacetate
      that were treated with a shortened 1-s dip, this smoke extract and one with
      reduced smoke flavor and color both produced a > 4.5-log reduction of L.
      monocytogenes on frankfurters when heated at 73.9 degrees C for 1 min, with no
      recoverable Listeria detected for 10 weeks when stored at 6.1 degrees C. When
      deli turkey breast chubs manufactured without lactate, diacetate, or nitrite were
      treated with a 1-s dip in combination with radiant-heat pasteurization (270
      degrees C), growth of L. monocytogenes was retarded but not prevented. However,
      in a similar study in which smoke extract treatment of deli turkey breast was
      combined with in-bag postpackage pasteurization (water submersion at 93.3 degrees
      C), a 60-, 45-, or even 30-s heat treatment resulted in a 2- to 3-log reduction
      of L. monocytogenes, with no growth on the meat during 10 weeks of storage at 6.1
      degrees C. These findings indicate that reduced-acid low-phenolic antimicrobial
      liquid smoke derivatives combined with surface pasteurization are capable of
      reducing or preventing growth of L. monocytogenes to meet the criteria for the
      U.S. Department of Agriculture Food Safety and Inspection Service Alternative 1
      process for ready-to-eat deli meat products manufactured without lactate or
      diacetate.

PMID- 18095427
TI  - Antimicrobial activity of clove and cinnamon essential oils against Listeria
      monocytogenes in pasteurized milk.
AB  - The antimicrobial activity of essential oils (EOs) of cinnamon bark, cinnamon
      leaf, and clove against Listeria monocytogenes Scott A were studied in
      semiskimmed milk incubated at 7 degrees C for 14 days and at 35 degrees C for 24
      h. The MIC was 500 ppm for cinnamon bark EO and 3,000 ppm for the cinnamon leaf
      and clove EOs. These effective concentrations increased to 1,000 ppm for cinnamon
      bark EO, 3,500 ppm for clove EO, and 4,000 ppm for cinnamon leaf EO when the
      semiskimmed milk was incubated at 35 degrees C for 24 h. Partial inhibitory
      concentrations and partial bactericidal concentrations were obtained for all the
      assayed EOs. The MBC was 3,000 ppm for the cinnamon bark EO, 10,500 ppm for clove
      EO, and 11,000 ppm for cinnamon leaf EO. The incubation temperature did not
      affect the MBC of the EOs but slightly increased the MIC at 35 degrees C. The
      increased activity at the lower temperature could be attributed to the increased
      membrane fluidity and to the membrane-perturbing action of EOs. The influence of
      the fat content of milk on the antimicrobial activity of EOs was tested in whole
      and skimmed milk. In milk samples with higher fat content, the antimicrobial
      activity of the EOs was reduced. These results indicate the possibility of using
      these three EOs in milk beverages as natural antimicrobials, especially because
      milk beverages flavored with cinnamon and clove are consumed worldwide and have
      been increasing in popularity in recent years.

PMID- 18095428
TI  - Enterotoxigenic and antibiotic resistance determination of Staphylococcus aureus
      strains isolated from food handlers in Gaborone, Botswana.
AB  - The prevalence, antibiotic resistance, and enterotoxigenic potential of
      Staphylococcus aureus strains from different anatomical sites on food handlers in
      Gaborone, Botswana, were determined. Of a total of 200 food handlers tested, 115
      (57.5%) were positive for S. aureus. Of the 204 S. aureus isolates, 63 (30.9%),
      91 (44.6%), and 50 (24.5%) were isolated from the hand, nasal cavity, and face,
      respectively, and 43 (21%) of the isolates were enterotoxigenic. The most
      prevalent enterotoxin was type A, which accounted for 34.9% of all the
      enterotoxigenic strains, and enterotoxin D was produced by the fewest number of
      strains (9.3%). Resistance to methicillin was encountered in 33 (22.4%) of the
      penicillin G-resistant isolates, and 9 (27.3%) of these methicillin-resistant
      isolates also were resistant to vancomycin. Nineteen antibiotic resistance
      profiles were determined, and the nasal cavity had the highest diversity of
      resistance profiles. The nasal cavity also had the highest number of resistant
      strains, 77 (53%), whereas the hand and face had 49 (32%) and 24 (16.0%)
      resistant strains, respectively. To reduce the Staphylococcus carriage rate among
      food handlers, training coupled with a commitment to high standards of personal
      and environmental hygiene is recommended.

PMID- 18095429
TI  - Effect of ozone and open air factor against aerosolized Micrococcus luteus.
AB  - Because of increased concerns over failures in cleaning, the role of bioaerosols,
      and the environmental and clinical persistence of pathogens, the evaluation of
      novel decontaminants is increasingly important. The bactericidal properties of
      open air factor (OAF; a collection of highly reactive chemical species) were
      identified in the 1970s; however, the potential practical applications of
      artificially generated OAF have been considered only recently. In this study, the
      effects of OAF against Micrococcus luteus were investigated. OAF was generated
      and distributed in a bioaerosol test chamber by delivery of monoterpenes into
      ozonated air (0.1 ppm) at concentrations of 2.0 (high), 0.75 (medium), or 0.3
      (low) mgm(-3) h(-1). M. luteus was aerosolized, and the number of culturable
      survivors was determined after 2, 5, 10, 20, and 60 min. Culturable bacteria were
      enumerated by aerobic plate counts in all-glass impinger fluid. Data were
      analyzed for statistical significance using one- or two-way analyses of variance.
      When aerosolized bacteria were exposed to ozone alone (0.05, 0.1, and 2 ppm), a
      significant (up to 3-log) reduction was observed at all concentrations, and the
      effect was time dependent. When exposed to the cyclic monoterpene alone, there
      were no significant differences between test samples and controls. When exposed
      to OAF (high and medium concentrations in 0.1 ppm ozone) there were significant
      differences after 20 min. These reductions were significantly greater than those
      achieved with ozone alone at 0.1 ppm. OAF is potentially an effective
      antibacterial agent that can reduce the microbial load in air. Because the
      technology uses reaction compounds naturally found in the environment, risks to
      health may be lower than those associated with ozone or other gaseous treatments.
      However, this hypothesis needs further investigation.

PMID- 18095430
TI  - Development of rapid real-time PCR and most-probable-number real-time PCR assays
      to quantify enterotoxigenic strains of the species in the Bacillus cereus group.
AB  - Members of the Bacillus cereus group may produce diarrheal enterotoxins and could
      be potential hazards if they enter the food chain. Therefore, a method capable of
      detecting all the species in the B. cereus group rather than B. cereus alone is
      important. We selected nhe as the target and developed a real-time PCR assay to
      quantify enterotoxigenic strains of the B. cereus group. The real-time PCR assay
      was evaluated with 60 B. cereus group strains and 28 others. The assay was also
      used to construct calibration curves for different food matrices and feces. The
      assay has an excellent quantification capacity, as proved by its linearity (R2 >
      0.993), wide dynamic quantification range (10(2) to 10(7) CFU/g for cooked rice
      and chicken, 10(3) to 10(7) CFU/ml for milk, and 10(4) to 10(7) CFU/g for feces),
      and adequate relative accuracy (85.5 to 101.1%). For the low-level
      contaminations, a most-probable-number real-time PCR assay was developed that
      could detect as low as 10(0) CFU/ml. Both assays were tested with real food
      samples and shown to beconsiderably appropriate for B. cereus group detection and
      quantification.

PMID- 18095431
TI  - Isolation and characterization of a psychrotolerant toxin producer, Bacillus
      weihenstephanensis, in liquid egg products.
AB  - A psychrotolerant bacteria of the Bacillus cereus group was found responsible for
      the spoilage of whole liquid egg products. By sequencing a 16S rRNA region and
      performing a PCR amplification of specific 16S rRNA and cspA signatures, a
      Bacillus weihenstephanensis was identified. Characterization of this strain shows
      its ability to grow in defined medium as well as in whole liquid egg at
      refrigerated temperatures. The strain isolated possesses genes encoding for
      hemolysin BL, nonhemolytic enterotoxin, and B. cereus enterotoxins and produces
      enterotoxins with cytotoxic activity in whole liquid egg, even at refrigerated
      temperatures. The isolate exhibits a clear ability to stick and form biofilms on
      stainless steel, the most common material used in egg breaking factories, as well
      as on model hydrophilic (glass) and hydrophobic (polytetrafluoroethylene)
      materials. These findings show the necessity to monitor for Bacillus
      contamination in egg products that are often used in the composition of
      particularly susceptible finished products such as cream, dessert, dairy, meat,
      and seafood.

PMID- 18095432
TI  - Chimeras of mature pediocin PA-1 fused to the signal peptide of enterocin P
      permits the cloning, production, and expression of pediocin PA-1 in Lactococcus
      lactis.
AB  - Chimeras of pediocin PA-1 (PedA-1), a bacteriocin produced by Pediococcus
      acidilactici PLBH9, fused to the signal peptide of enterocin P (EntP), a sec
      dependent bacteriocin produced by Enterococcus faecium P13, permitted the
      production of PedA-1 in Lactococcus lactis. Chimeric genes encoding the EntP
      signal peptide (SP(entP)) fused to mature PedA-1 (pedA), with or without its
      immunity gene (pedB), were cloned into the expression vector pMG36c to generate
      the recombinant plasmids pMPP9 (SP(entP):pedA) and pMPP14i (SP(entP):pedA +
      pedB). Transformation of competent L. lactis subsp. lactis IL1403, L. lactis
      subsp. cremoris NZ9000, and L. lactis subsp. lactis DPC5598 with the recombinant
      plasmids has permitted the detection and quantitation of PedA-1 and the
      coproduction of nisin A and PedA-1 in supernatants of producer cells with
      specific anti-PedA-1 antibodies and a noncompetitive indirect enzyme-linked
      immunosorbent assay. Recombinant L. lactis hosts carrying pMPP9 or pMPP14i
      displayed antimicrobial activity, suggesting that mature PedA-1 fused to SP(EntP)
      is the minimum requirement for the synthesis, processing, and secretion of
      biologically active PedA-1 in L. lactis. However, the production and
      antimicrobial activity of the PedA-1 produced by L. lactis was lower than that
      produced by the P. acidilactici control strains.

PMID- 18095433
TI  - Characterization of the gastrointestinal mucosa-associated microbiota of pigs and
      chickens using culture-based and molecular methodologies.
AB  - The microbiota of the gastrointestinal tract (GIT) can play an important role in
      the healthy status of farm animals and in the safety of the whole food chain. In
      this study, the mucosa-associated microbiota of the GIT of pigs and chickens was
      analyzed by culture methods and fluorescence in situ hybridization combined with
      flow cytometry (FCM-FISH). In all pig GIT sections, lactic acid bacteria,
      Enterobacteriaceae, Atopobium, Bacteroides, and Clostridium histolyticum were the
      predominant bacterial groups. Atopobium, Bifidobacterium, Bacteroides, and
      Lactobacillus were detected at higher levels (P < 0.05) in the intestine than in
      the stomach. In all broilers' GIT sections, lactic acid bacteria, Atopobium,
      Bacteroides, and Escherichia coli were the predominant bacterial groups.
      Atopobium, Bifidobacterium, E. coli, and Eubacterium rectale--Clostridium
      coccoides counts were significantly higher (P < 0.05) in the crop, while those of
      Bacteroides and Lactobacillus were higher (P < 0.05) in the large intestine.
      Lactic acid bacteria were one of the predominant GIT mucosa-associated bacteria
      of pigs and broilers, which could be an index of their healthy status. FCM-FISH
      analysis also allowed the detection of bacterial groups hard to cultivate yet
      quantitatively important. The distribution of Lactobacillus and Bacteroides
      followed the same trend in both animal species, whereas that of Atopobium and
      Bifidobacterium was the opposite. These results contribute to the knowledge on
      the diversity and distribution of the animal GIT mucosa-associated microbiota.

PMID- 18095434
TI  - Pulsed-plasma gas-discharge inactivation of microbial pathogens in chilled
      poultry wash water.
AB  - A pulsed-plasma gas-discharge (PPGD) system was developed for the novel
      decontamination of chilled poultry wash water. Treatment of poultry wash water in
      the plasma generation chamber for up to 24 s at 4 degrees C reduced Escherichia
      coli NCTC 9001, Campylobacter jejuni ATCC 33560, Campylobacter coli ATCC 33559,
      Listeria monocytogenes NCTC 9863, Salmonella enterica serovar Enteritidis ATCC
      4931, and S. enterica serovar Typhimurium ATCC 14028 populations to non
      detectable levels (< or = 8 log CFU/ml). Although similar PPGD treatments at 4
      degrees C also produced significant reductions (> or = 3 log CFU/ml) in
      recalcitrant B. cereus NCTC 11145 endospore numbers within 30 s, the level of
      endospore reduction was dependent on the nature of the sparged gas used in the
      plasma treatments. Scanning electron microscopy revealed that significant damage
      occurred at the cellular level in PPGD-treated test organisms. This
      electrotechnology delivers energy in intense ultrashort bursts, generating
      products such as ozone, UV light, acoustic and shock waves, and pulsed electric
      fields that have multiple bactericidal properties. This technology offers an
      exciting complementary or alternative approach for treating raw poultry wash
      water and for preventing cross-contamination in processing environments.

PMID- 18095435
TI  - Comparing uncertainty resulting from two-step and global regression procedures
      applied to microbial growth models.
AB  - Two different microbial modeling procedures were compared and validated against
      independent data for Listeria monocytogenes growth. The most generally used
      method is two consecutive regressions: growth parameters are estimated from a
      primary regression of microbial counts, and a secondary regression relates the
      growth parameters to experimental conditions. A global regression is an
      alternative method in which the primary and secondary models are combined, giving
      a direct relationship between experimental factors and microbial counts. The
      Gompertz equation was the primary model, and a response surface model was the
      secondary model. Independent data from meat and poultry products were used to
      validate the modeling procedures. The global regression yielded the lower
      standard errors of calibration, 0.95 log CFU/ml for aerobic and 1.21 log CFU/ml
      for anaerobic conditions. The two-step procedure yielded errors of 1.35 log
      CFU/ml for aerobic and 1.62 log CFU/ ml for anaerobic conditions. For food
      products, the global regression was more robust than the two-step procedure for
      65% of the cases studied. The robustness index for the global regression ranged
      from 0.27 (performed better than expected) to 2.60. For the two-step method, the
      robustness index ranged from 0.42 to 3.88. The predictions were overestimated
      (fail safe) in more than 50% of the cases using the global regression and in more
      than 70% of the cases using the two-step regression. Overall, the global
      regression performed better than the two-step procedure for this specific
      application.

PMID- 18095436
TI  - Development and implementation of hazard analysis and critical control point
      plans by several U.S. feed manufacturers.
AB  - The commitment to consumer food safety, global trade, and proposed new
      regulations by the U.S. Food and Drug Administration Center for Veterinary
      Medicine has led to increased adoption of hazard analysis and critical control
      point (HACCP) by the U.S. feed industry. A project supported by the U.S.
      Department of Agriculture Integrated Food Safety Initiate titled "Development and
      Implementation of a Voluntary HACCP Program for the US Feed Industry" enabled
      faculty from three land grant universities to assist individuals from 14 feed
      companies that collectively manufacture 15 million metric tons of feed in 100
      facilities to develop HACCP plans. The process flow in these plans averaged 20
      steps, and the most detailed plan included 60 process steps. Chemical hazards
      were more commonly identified in HACCP plans (average of four hazards per plan)
      than were biological hazards (average of one per plan). The most prevalent
      chemical hazards were cross-contamination of type A medicated articles and type B
      medicated feeds, aflatoxin, and wrong ingredient inclusion in feed. The most
      common biological hazard was mammalian protein contamination of feed ingredients
      and finished feed for cattle. An assessment of time and costs associated with
      developing HACCP plans revealed that approximately 29% of the companies needed
      additional personnel or additional equipment to implement a HACCP plan, and on
      average 268 additional person hours were needed to develop and implement a HACCP
      plan. Plan design, compliance monitoring, and record keeping were the three most
      time-consuming activities needed for developing and implementing a HACCP plan.
      The average cost of additional equipment needed to implement a HACCP plan was
      $250.

PMID- 18095437
TI  - Natural occurrence of aflatoxin B1 in marketed foods and risk estimates of
      dietary exposure in Koreans.
AB  - Aflatoxin B1 (AFB1) is an unavoidable food contaminant. To evaluate the potential
      health risk of AFB1 to Koreans posed by food consumption, we determined the
      natural occurrence of AFB1 in food and estimated the excess risk for liver cancer
      through dietary exposure to AFB1. A total of 694 food samples collected from six
      different regions of South Korea were analyzed for their AFB, content. One
      hundred four of the 694 samples were found to give positive enzyme-linked
      immunosorbent assay (ELISA) readings for AFB1 and were further investigated with
      high-performance liquid chromatography. Thirty-two samples, including 2 maize
      samples, 3 soybean products, 20 peanut samples, nut samples, and their products,
      and 7 spices, were found to be contaminated with AFB1 (4.6% incidence), up to
      48.6 microg kg(-1). The level of AFB1 contamination in 28 of the 32 food products
      was below 10 microg kg(-1), which is the legal tolerance limit in Korea. From
      data on daily food consumption, the exposure dose of AFB1 was estimated to be
      6.42 x 10(-7) mg kg(-1) body weight (bw) day(-1). The major contributors to the
      dietary intake of AFB1 were soybean paste and soy sauce, which composed 91% of
      the total exposure to AFB1. The excess risk of liver cancer for those exposed to
      AFB1 through food intake was estimated to be 5.78 x 10(-6) for hepatitis B
      negative individuals and 1.48 x 10(-4) for hepatitis B-positive individuals.
      These results suggest that special consideration is required to reduce the intake
      of AFB1 in hepatitis B-positive individuals.

PMID- 18095438
TI  - Production of secondary metabolites by some terverticillate penicillia on
      carbohydrate-rich and meat substrates.
AB  - Most terverticillate penicillia isolated from dry-cured meat products are
      toxigenic, but their ability to produce hazardous metabolites on meat-based
      substrates is not well known. The production of extrolites by selected
      terverticillate penicillia isolated from dry-cured ham has been studied on
      carbohydrate-rich media (malt extract agar, Czapek yeast autolysate agar, rice
      extract agar, and rice), meat extract triolein salt agar, and ham slices.
      Chloroform extracts from the selected strains grown on malt extract agar were
      toxic for the brine shrimp (Artemia salina) larvae and VERO cells at a
      concentration of 2 mg/ml, but 0.02 mg/ml produced no toxic effect. Analysis by
      high-pressure liquid chromatography (HPLC) coupled with photodiode array
      detection (DAD) or with mass spectrometry (MS) and an atmospheric pressure
      chemical ionization (APCI) source revealed different biologically active
      metabolites: cyclopiazonic acid and rugulovasine A from Penicillium commune;
      verrucosidin, anacine, puberuline, verrucofortine, and viridicatols from
      Penicillium polonicum; arisugacin and viridicatols from Penicillium echinulatum;
      and compactin and viridicatols from Penicillium solitum. Most of these
      metabolites, including the amino acid-derived compounds, were produced in the
      media containing high levels of carbohydrates. High concentrations of nitrogen
      compounds in the medium does not imply a greater production of the metabolites
      studied, not even those derived from the amino acids. However, molds growing on
      dry-cured ham are able to synthesize limited amounts of some secondary
      metabolites, a fact not previously reported. The combination of HPLC coupled with
      DAD and MS-APCI was useful for identification of closely related terverticillate
      Penicillium species from dry-cured ham. These techniques could be used to
      characterize the risk associated with the potential production of secondary
      metabolites in cured meats.

PMID- 18095439
TI  - High hydrostatic pressure and UV light treatment of produce contaminated with
      Eimeria acervulina as a Cyclospora cayetanensis surrogate.
AB  - The prevalence, size, genome, and life cycle of Eimeria acervulina make this
      organism a good surrogate for Cyclospora cayetanensis, a protozoan that causes
      gastroenteritis in humans, including recent outbreaks in the United States and
      Canada associated with contaminated raspberries and basil. Laboratory studies of
      C. cayetanensis are difficult because of the lack of readily available oocysts
      and of infection models and assays. UV radiation and high-hydrostatic-pressure
      processing (HPP) are both safe technologies with potential for use on fresh
      produce. Raspberries and basil were inoculated with sporulated E. acervulina
      oocysts at high (10(6) oocysts) and low (10(4) oocysts) levels, and inoculated
      and control produce were treated with UV (up to 261 mW/cm2) or HPP (550 MPa at 40
      degrees C for 2 min). Oocysts recovered from produce were fed to 3-week-old
      broiler chickens, which were scored for weight gain, oocyst shedding, and lesions
      at 6 days postinoculation. Oocysts exhibited enhanced excystation on raspberries
      but not on basil. Birds fed oocysts from UV-treated raspberries had reduced
      infection rates, which varied with oocyst inoculum level and UV intensity. Birds
      fed oocysts from UV-treated raspberries (10(4) oocysts) were asymptomatic but
      shed oocysts, and birds fed oocysts from UV-treated basil (10(4) oocysts) were
      asymptomatic and did not shed oocysts. Birds fed oocysts from HPP-treated
      raspberries and basil were asymptomatic and did not shed oocysts. These results
      suggest that UV radiation and HPP may be used to reduce the risk for
      cyclosporiasis infection associated with produce. Both treatments yielded healthy
      animals; however, HPP was more effective, as indicated by results for produce
      with higher contamination levels.

PMID- 18095440
TI  - Characterization of Shiga toxigenic Escherichia coli isolated from foods.
AB  - The aim of this study was to characterize Shiga toxigenic Escherichia coli (STEC)
      by PCR using strains isolated from ham, beef, and cattle in Colombia. A total of
      189 E. coli strains were tested for the presence of the uidA, stx1, and stx2
      genes, and identification was confirmed by the automated PCR BAX system for E.
      coli O157:H7. Genes encoding Shiga-like toxins (stx) were found in eight (6.06%)
      of 132 strains previously isolated from minced beef; four (50%) of these strains
      yielded amplification products for both toxin genes (stx1 and stx2), and four
      (50%) yielded products only for the stx2 toxin. None of the strains analyzed were
      positive by PCR for the presence of the single base-pair mutation in the uidA
      gene from E. coli O157:H7; these results were confirmed by the BAX system
      analysis. A multiplex PCR assay was standardized for the three genes. Results
      from this study confirmed previous data about the low prevalence of E. coli
      O157:H7 and Shiga-like toxins in Colombia and is the first known report of the
      prevalence of non-O157 enterohemorrhagic E. coli in this country.

PMID- 18095441
TI  - Effectiveness of lemon juice in the elimination of Salmonella Typhimurium in
      stuffed mussels.
AB  - Street foods are becoming more and more prominent in countries all over the
      world. There are many reports of disease due to consumption of street foods
      contaminated by pathogens. With the modern trend toward more natural
      preservatives, the use of organic acids can achieve a good microbiological safety
      in food. In the present study, stuffed mussels were inoculated with Salmonella
      Typhimurium suspension to provide initial populations of approximately 6 and 3
      log CFU/g. After inoculation, samples were treated with fresh lemon juice and
      lemon dressing for 0, 5, and 15 min, and pathogens were enumerated by using
      direct plating on brilliant green agar. Treatment of stuffed mussels inoculated
      at high inoculum level, with lemon juice and lemon dressing for different
      exposure times caused reduction ranging between 0.25 and 0.56 log CFU/g and 0.5
      and 0.69 log CFU/g, respectively, whereas in stuffed-mussel samples inoculated at
      low level, lemon juice and lemon dressing caused 0.08 to 0.25 log CFU/g and 0.22
      to 0.78 log CFU/g reductions, respectively. Results of the study showed that both
      lemon juice and lemon dressing used as flavoring and acidifying agents for
      stuffed mussels caused slight decrease in Salmonella Typhimurium as an immediate
      inhibitor, but this effect increased by time. However, treatment of stuffed
      mussels with the inhibitors until 15 min is not enough to prevent Salmonella
      Typhimurium outbreaks related to stuffed mussels.

PMID- 18095442
TI  - Different enrichment procedures for recovery of Listeria monocytogenes from raw
      chicken samples can affect the results of detection (by chromogenic plating or
      real-time PCR) and lineage or strain identification.
AB  - This study aimed to evaluate the effect of different enrichment procedures on the
      detection of Listeria monocytogenes in food, by a comparison of subculture onto
      chromogenic agar with real-time PCR. Two different culture media, the primary and
      secondary enrichment broths of the U.S. Food Safety and Inspection Service (FSIS)
      method used for PCR detection of L. monocytogenes, were compared for the primary
      enrichment of retail ground chicken samples. L. monocytogenes was detected after
      the completion of each enrichment procedure in 63% (complete FSIS procedure) and
      60% (plain FSIS secondary enrichment broth incubated for 48 h) of the samples by
      both culture and PCR, whereas a combination of the results for the two enrichment
      procedures revealed 86% of the samples to be positive. Most of the samples
      analyzed contained a mixture of lineage I and II strains, and their ratio varied
      for each enrichment procedure. This mixture could have a significant effect on
      the result of detection of L. monocytogenes for each individual sample,
      explaining the increase in positive samples when the results of the two
      enrichment procedures were combined. The use of different isolation procedures
      can affect the specific samples identified as positive and the specific strains
      isolated.

PMID- 18095443
TI  - Real-time PCR detection of Staphylococcus aureus in milk and meat using new
      primers designed from the heat shock protein gene htrA sequence.
AB  - Staphylococcus aureus may cause foodborne disease outbreaks and staphylococcal
      infections and is one of the major causes of mastitis. Rapid and reliable methods
      for detection of this microorganism in milk and other foods are needed. In this
      study, we designed a primer set from the sequence of the heat shock protein gene
      htrA, a gene coding for high-temperature-requirement A (HtrA) protein, and used
      it for real-time PCR detection of S. aureus isolates: 16 reference strains and 40
      strains isolated from food-poisoning cases. All strains tested generated positive
      results. Bacterial strains other than S. aureus, including strains of other
      Staphylococcus species, did not produce positive results. When this primer set
      was used for the real-time PCR detection of S. aureus in milk and meat samples
      without the preenrichment step, samples with target cell numbers greater than
      10(3) CFU/ml or CFU/g could be detected, indicating the potential quantitative
      ability of this real-time PCR assay. With a 10-h preenrichment step, however, a
      detection limit of 1 CFU/ml or CFU/g could be obtained.

PMID- 18095444
TI  - Evaluation of the effect of acetylsalicylic acid on Clostridium botulinum growth
      and toxin production.
AB  - The Republic of Georgia (ROG) has the highest incidence of botulism among all
      countries in the world, with most cases attributed to home-preserved vegetables.
      Based on epidemiologic data, the occurrence of botulism in ROG is lower in areas
      where aspirin (active ingredient, acetylsalicylic acid [ASA]) is added to home
      canned vegetables. The objective of this study was to evaluate, with a broth
      medium, the antibotulinal activity of ASA to determine the possible role of ASA
      in preventing botulinum toxin production in home-canned vegetables. Trypticase
      peptone-glucose-yeast (TPGY) broth (pH 7.0) with 0, 0.3, and 0.6 mg of ASA per ml
      was inoculated with a 10-strain mixture of proteolytic Clostridium botulinum type
      A and B spores at ca. 10(3) spores per ml. The inoculated broths were incubated
      at 31 degrees C under anaerobic conditions, and C. botulinum growth and botulinum
      toxin production were determined for up to 36 h. Results showed ASA in broth
      delayed (time to initial detectable toxin produced and amount of toxin produced),
      but did not prevent, both growth and toxin production by C. botulinum. These
      results would not provide a definitive explanation for differences in toxin
      production in canned vegetables prepared with and without aspirin.

PMID- 18095445
TI  - Microbial survey of selected Ontario-grown fresh fruits and vegetables.
AB  - Recent produce-related outbreaks have been receiving heightened media coverage,
      which has increased public concern toward the safety of fresh fruits and
      vegetables. In response, the microbial contamination of Ontario-grown fresh
      fruits and vegetables was evaluated by the Ontario Ministry of Agriculture, Food
      and Rural Affairs during the summer of 2004. Prior to this survey, information
      specific to the microbial contamination of Ontario-produced fruits and vegetables
      was limited. This nonregulatory survey had two objectives: (i) to obtain a
      general microbiological profile of selected fruits and vegetables produced in
      Ontario and (ii) to use the information and knowledge gained from this survey to
      direct and support future on-farm food safety research and food safety programs
      to manage potential risks. In all, 1,183 samples, including muskmelon (151),
      scallions and green onions (173), leaf lettuce (263), organic leaf lettuce (112),
      head lettuce (155), parsley (127), cilantro (61), and fresh market tomatoes
      (141), were collected and analyzed. Samples were analyzed for Salmonella,
      Shigella, and generic E. coli. Enrichment cultures positive for E. coli were
      further assessed for verotoxigenicity. One sample each of Roma tomato and organic
      leaf lettuce were positive for Salmonella, with no samples yielding Shigella or
      verotoxigenic E. coli. The E. coli prevalence was highest in parsley (13.4%),
      followed by organic leaf lettuce (11.6%), leaf lettuce (6.5%), scallions (6.4%),
      cilantro (4.9%), muskmelon (1.3%), head lettuce (0%), and fresh market tomatoes
      (0%). These findings, in combination with foodborne illness data, will help
      target those commodities that require more focused risk mitigation efforts.

PMID- 18095446
TI  - Bacterial contamination of sago starch in Papua New Guinea.
AB  - Sago starch is an important food in lowland Papua New Guinea. Extraction of the
      starch from the palm and storage were performed by way of traditional methods
      that have been used for thousands of years. Currently, very little is known about
      the microbiology of sago starch. Sago samples were collected from areas of high
      starch utilization and analyzed for the presence of bacterial pathogens and
      indicator organisms. Storage methods and duration were recorded at the time of
      collection, and pH and water activity on arrival at the laboratory. Sago starch
      was found to harbor high levels of fecal contamination, as well as various food
      pathogens including Salmonella, Bacillus cereus, and coagulase-positive
      staphylococci. Clostridium perfringens was only present infrequently in samples
      and in very low numbers, while Listeria monocytogenes was not isolated from sago
      starch. The presence of high levels of fecal contamination in sago starch is of
      particular concern, and may contribute to diarrheal disease in rural Papua New
      Guinea.

PMID- 18095447
TI  - Effect of hand wash agents on controlling the transmission of pathogenic bacteria
      from hands to food.
AB  - The goals of this study were to evaluate the effectiveness of two hand wash
      regimens in reducing transient bacteria on the skin following a single hand wash
      and the subsequent transfer of the bacteria to a ready-to-eat food item, freshly
      cut cantaloupe melon. The number of bacteria recovered from hands and the
      quantity transferred to the melon were significantly less following the use of an
      antibacterial soap compared with plain soap. The antimicrobial soap achieved > 3
      log reductions versus Escherichia coli and 3.31- and 2.83-log reductions versus
      Shigella flexneri. The plain soap failed to achieve a 2-log reduction against
      either organism. The bacteria recovered from the melon handled by hands treated
      with antimicrobial hand soap averaged 2 log. Melon handled following hand washing
      with plain soap had > 3 log bacteria in the experiments. Based on previously
      published feeding studies, an infection rate in the range of approximately 15 to
      25% would be expected after ingesting melon containing 2 log CFU compared with
      ingesting greater than the 3 log transferred from hands washed with plain soap,
      which would result in a higher infection attack rate of 50 to 80%. The data thus
      demonstrate there is a greater potential to reduce the transmission and
      acquisition of disease through the use of an antimicrobial hand wash than through
      the use of plain soap.

PMID- 18095448
TI  - Cleaning and handling implements as potential reservoirs for bacterial
      contamination of some ready-to-eat foods in retail delicatessen environments.
AB  - This study assessed the association of bacteria with cleaning tools, such as
      floor mops (n = 25) and cleaning cloths (n = 39), and handling devices, such as
      disposable plastic gloves (n = 20), used during filled baguette and assorted
      salad preparation in four selected retail delicatessens in Johannesburg, South
      Africa. Samples of each cleaning or handling tool were prepared for aerobic
      (APC), coliform (CC), Escherichia coli (EC), Bacillus cereus (BCC), and
      Staphylococcus aureus (SAC) counts, as well as tested for the incidence of
      Listeria monocytogenes (LM) and Salmonella (SALM) by standard plating methods.
      Bacterial populations attached to the cleaning and handling tools were observed
      by scanning electron microscopy (SEM). Ten selected gram-positive isolates were
      further analyzed by 16S rRNA sequence analysis and compared with isolates from
      filled baguettes and assorted salads. The floor mops consistently yielded the
      highest APCs, CCs, and ECs (5.7, 4.1, and 3.0 log CFU/g, respectively), while
      gloves had the lowest corresponding counts (3.6, 2.0, and 1.0 log CFU/g,
      respectively). Low BCCs and SACs were recorded in this study (ca. 1.2 log CFU/g),
      while SALM and LM were each detected in five cleaning tool samples. SEM showed
      rods and cocci attached to handling and cleaning tools. Furthermore, results of
      16S rRNA sequence analysis indicated that several gram-positive isolates were
      identified as S. aureus, Staphylococcus pasteuri, Staphylococcus sciuri, and
      Enterococcus faecalis. Genetically similar strains (100% similarity) were
      isolated from cleaning and handling tools and associated ready-to-eat (RTE)
      foods. Cleaning and handling tools may act as reservoirs of contamination for RTE
      foods during preparation in retail delicatessens in South Africa. The transfer of
      potential pathogens, such as S. aureus, to foods from cleaning and handling tools
      may hold food safety implications.

PMID- 18095449
TI  - Impact of water activity and temperature on growth and ochratoxin A production of
      two Aspergillus carbonarius isolates from wine grapes in Greece.
AB  - The aim of this study was to determine the effects of water activity (a(w); 0.85
      to 0.98) and temperature (10 to 40 degrees C) on the radial growth rate and
      ochratoxin A (OA) production of two Aspergillus carbonarius isolates in vitro.
      The isolates were obtained from wine grapes cultivated in Greece, and the trial
      was conducted with a synthetic grape juice medium similar in composition to
      grapes between veraison (beginning of color change) and ripeness. Fungal growth
      and OA production data were collected for 55 days. Response surface curves and
      cardinal values for a(w) and temperature were obtained using multiple regression
      analysis. The lag phase lasted from less than 1 to 10 days. Both isolates grew
      optimally at 30 to 35 degrees C and 0.96 a(w), but maximum OA production occurred
      under suboptimal growth conditions (15 to 20 degrees C and 0.93 to 0.96 a(w)).
      Growth also was observed at 0.85 a(w) and 25 degrees C, however at this same a(w)
      the fungus failed to produce mycelium at any other temperatures tested. The
      isolates produced OA at 15 to 30 degrees C and 0.90 to 0.98 a(w). Maximum OA
      production was detected after 25 days of incubation at 20 degrees C and 0.96 a(w)
      and was 3.14 and 2.67 microg g(-1), respectively, for the two strains. The
      isolated strains used in this study were more xerotolerant than others from the
      Mediterranean basin. These data will allow producers to identify and thus monitor
      critical environmental conditions effectively in wine grapes. These data also
      increase the knowledge base concerning the ability of A. carbonarius to grow and
      produce toxin under different ecological conditions and can contribute to the
      development of secondary models for the prediction and risk assessment of OA in
      wine production.

PMID- 18095450
TI  - Hepatitis E virus RNA in commercial porcine livers in The Netherlands.
AB  - Human hepatitis E virus (HEV) infections by genotype 3 strains in industrialized
      countries are hypothesized to be caused by pigs. To examine this hypothesis, the
      potential health risks of transmission routes should be examined. Possible
      foodborne transmission was studied by quantifying the presence and infectivity of
      HEV in commercial porcine livers in The Netherlands. A comparison of four tissue
      disruption and seven RNA extraction methods revealed that mechanical disruption
      followed by silica-based RNA extraction gave the highest RNA yields and was
      therefore employed on commercial porcine livers. Four (6.5%) of 62 porcine livers
      were HEV RNA positive by reverse transcriptase PCR and Southern blot
      hybridization. Each positive liver was estimated to contain approximately 65 PCR
      detectable units per g. Sequences were obtained for three of four positive livers
      and classified as HEV genotype 3. Ninety-three percent similarity to Dutch human
      HEV sequences and 97% similarity to Dutch swine HEV sequences were observed. To
      determine whether positive livers contained infectious HEV particles, extracts
      from livers with known HEV RNA sequences were inoculated intravenously in pigs.
      Two control pigs were included: one was inoculated with a high dose known to
      result in infection (10(4) PCR-detectable units of HEV RNA), and the other was
      inoculated with a lower concentration of virus that equaled the concentration of
      PCR-detectable units in commercial livers ( approximately 20 PCR-detectable
      units). Infection was observed in the high-dose control, but not in other pigs,
      suggesting a dose-dependent response in pigs. Hence, the implications of HEV RNA
      in commercial porcine livers in The Netherlands are unknown. However, HEV RNA is
      present in commercial porcine livers, and sufficient heating of porcine livers
      before consumption as precautionary measure is recommended.

PMID- 18095451
TI  - Evaluation of a fluid versus a powder pepsin formulation to detect Trichinella
      spiralis larvae in meat samples by a digestion technique.
AB  - Pepsin powder constitutes a health risk, potentially causing severe allergic
      reactions to those handling the chemical. A fluid pepsin formulation was produced
      and tested, first in a preliminary study and then in a ring trial encompassing
      four European National Reference Laboratories (NRLs). The purpose of each trial
      was to ascertain and compare the action of pepsin powder with that of the pepsin
      fluid for digesting meat and liberating encapsulated Trichinella spiralis larvae
      for subsequent counting. The quality of digestion was furthermore evaluated by
      assessing the visibility through the digestion fluid and the amount of debris
      remaining after digestion. For the ring trial, at each laboratory 20 blinded
      replicate 100-g samples of pork meat containing a known number of encapsulated T.
      spiralis larvae (0 to 30) were digested by the magnetic stirrer method using
      either the standard pepsin powder (10 samples) or the pepsin fluid (10 samples).
      With an average recovery rate of 70 to 80%, all NRLs found the pepsin fluid and
      pepsin powder to be equally effective. The NRLs also found no difference between
      the two pepsin formulations with regard to debris remnants or visibility through
      the digestion fluid. The use of pepsin fluid may therefore constitute an
      improvement of the digestion procedure for the analysts involved.

PMID- 18095452
TI  - Cloth-based hybridization array system for expanded identification of the animal
      species origin of derived materials in feeds.
AB  - A cloth-based hybridization array system (CHAS) previously developed for the
      detection of animal species for which prohibited materials have been specified
      (cattle, sheep, goat, elk, and deer) has been expanded to include the detection
      of animal species for which there are no prohibitions (pig and horse) in Canadian
      and American animal feeds. Animal species were identified by amplification of
      mitochondrial DNA sequences by PCR and subsequent hybridization of the amplicons
      with an array of species-specific oligonucleotide capture probes immobilized on a
      polyester cloth support, followed by an immunoenzymatic assay of the bound PCR
      products. The CHAS permitted sensitive and specific detection of meat meals from
      different animal species blended in a grain-based feed and should provide a
      useful adjunct to microscopic examination for the identification of prohibited
      materials in animal feeds.

PMID- 18095453
TI  - Fate of sympathetic trunk ganglia after cutting in German meat plants.
AB  - To minimize risks from pathogenic prion proteins, particular tissues from bovines
      and other ruminants have been declared specified risk materials (SRMs), which are
      required to be removed from the food chain. However, in particular for the
      sympathetic trunk (ST) as a part of the autonomous nervous system (ANS), which
      represents a potential transfer route for abnormal prion proteins (PrP(Sc)), this
      is not the case. Consequently, its destination during cutting procedures deserves
      attention. In this survey, the handling of the ST in beef cutting plants was
      recorded during ongoing work. To ease these observations, the ST was separated
      into five parts, and eight destinations for cuts were identified. By means of an
      observation sheet, the destination of the respective tissue was recorded. About
      one-third of the ST went into human consumption, another one-third was disposed
      of as SRMs, and the last one-third was used for nonfood purposes or disposed of.
      The rear thoracic and sacral ganglia primarily remained naturally connected to
      the bones going as SRMs. The stellate, front thoracic, and lumbar ganglia went in
      a different percent into the food chain. Frequently, workers in the same plant
      decided differently, even from case to case, on the destination of the tissue,
      which indicates a lack of standardization.

PMID- 18095454
TI  - Content of toxic heavy metals (mercury, lead, and cadmium) in canned variegated
      scallops (Chlamys varia).
AB  - The concentrations of three toxic heavy metals, mercury (Hg), lead (Pb), and
      cadmium (Cd), were determined in preserved variegated scallops (Chlamys varia,
      Bivalvia, Mollusca), which are often consumed in Tenerife (Canary Islands,
      Spain). A total of 300 samples of seven commercial brands (A, B, D, H, J, L, and
      M) and one processed product ("scallop sauce") were analyzed. Samples were
      collected weekly in a major shopping area in Santa Cruz de Tenerife during a 12
      month period. The concentrations of lead and mercury were far below the maximum
      limit permitted for human consumption by the European Communities Commission
      regulation (EC) 466/2001 (1 and 0.5 mg kg(-1) wet weight for Pb and Hg,
      respectively). Concentrations of cadmium were close to the maximum limit
      permitted by regulation (EC) 466/2001 (1 mg kg(-1) wet weight).

PMID- 18095455
TI  - Identification and toxigenic potential of the industrially important fungi,
      Aspergillus oryzae and Aspergillus sojae.
AB  - Mold strains belonging to the species Aspergillus oryzae and Aspergillus sojae
      are highly valued as koji molds in the traditional preparation of fermented
      foods, such as miso, sake, and shoyu, and as protein production hosts in modern
      industrial processes. A. oryzae and A. sojae are relatives of the wild molds
      Aspergillus flavus and Aspergillus parasiticus. All four species are classified
      to the A. flavus group. Strains of the A. flavus group are characterized by a
      high degree of morphological similarity. Koji mold species are generally
      perceived of as being nontoxigenic, whereas wild molds are associated with the
      carcinogenic aflatoxins. Thus, reliable identification of individual strains is
      very important for application purposes. This review considers the pheno- and
      genotypic markers used in the classification of A. flavus group strains and
      specifically in the identification of A. oryzae and A. sojae strains. Separation
      of A. oryzae and A. sojae from A. flavus and A. parasiticus, respectively, is
      inconsistent, and both morphologic and molecular evidence support conspecificity.
      The high degree of identity is reflected by the divergent identification of
      reference cultures maintained in culture collections. As close relatives of
      aflatoxin-producing wild molds, koji molds possess an aflatoxin gene homolog
      cluster. Some strains identified as A. oryzae and A. sojae have been implicated
      in aflatoxin production. Identification of a strain as A. oryzae or A. sojae is
      no guarantee of its inability to produce aflatoxins or other toxic metabolites.
      Toxigenic potential must be determined specifically for individual strains. The
      species taxa, A. oryzae and A. sojae, are currently conserved by societal issues.

PMID- 18095456
TI  - [Mechanism underlying iron metabolism: involvement of mitochondria in cellular
      iron sensing].

PMID- 18095457
TI  - [Biology of the pathogenic bacterial genome: impact of survival strategy in
      pathogenic bacteria].

PMID- 18095458
TI  - [Specificity and diversity of Rab family GTPases in membrane traffic].

PMID- 18095459
TI  - [Domain structure of ADAM family proteins].

PMID- 18095460
TI  - [ER stress signaling in pancreatic beta-cells].

PMID- 18095461
TI  - [Novel evolutional relationship in sugar metabolic pathways of microorganisms].

PMID- 18095462
TI  - [Mechanisms of membrane biogenesis in autophagy].

PMID- 18095463
TI  - [Mechanism of nucleosome assembly/disassembly mediated by histone chaperone CIA;
      implications for nucleosome semi-conservative replication].

PMID- 18095464
TI  - [Antibiotic susceptibility of Neisseria meningitidis from healthy and diseased
      persons in Japan].
AB  - We examined the susceptibilities of 100 Neisseria meningitidis strains isolated
      between 1990 and 2004 to 12 antimicrobial agents, finding the MIC50 to be 0.031
      microg/mL and that of MIC90 of benzylpenicillin (PCG), a type of penicillin, to
      be 0.063 microg/mL. Two strains showed intermediate resistance (MIC of 0.125-0.25
      microg/mL). Two strains of the same origin also showed intermediate resistance
      (0.25-1 microg/mL) to ampicillin (ABPC). For cephems, MIC50 and MIC90 of
      cefotaxime (CTX) were both 0.004 microg/mL, while the MICs of ceftriaxone (CTRX)
      were all 0.004 microg/mL, showing the strongest antibacterial spectrum. The three
      carbapenems surveyed meropenem (MEPM), panipenem (PAPM), and imipenem (IPM) also
      had a strong antibacterial spectrum in ascending order, with the MIC50 and MIC90
      of MEPM, which was lowest, being 0.008 microg/mL and 0.016 microg/mL. Some 97% of
      MICs for ciprofloxacin (CPFX) were 0.004 microg/mL but 3 strains showed
      resistance (0.125 microg/mL). No difference was seen between MICs of N.
      meningitidis strains originated from meningitis patients, patients other than
      meningitis, and healthy carriers. No difference was seen in MICs by serogroup (A,
      B, C, Y, W135 and NG).

PMID- 18095465
TI  - [Correlation between measles-neutralizing antibody and HI antibody, between
      measles-neutralizing antibody and PA antibody among pregnant women, and
      protective levels of three titration types].
AB  - When measles antibody levels among pregnant women were measured with measles
      hemagglutinin inhibition (HI), 31% of subjects had negative HI antibody titers.
      When the same blood samples were tested with measles gelatin particle
      agglutination (PA) and neutralizing (NT), the percentages of those with negative
      antibody levels were 1% and 3%. We conducted the correlation between antibody
      titers measured by the three types of titration. Correlation between NT and HI
      antibody titers higher than 1:8 and that between NT and PA antibody titers were
      good, but 81% of subjects whose HI antibody titer was below 1:8 and all women
      with HI antibody of 1:8 were found to have NT antibody titer higher than 1:4. NT
      antibody titer higher than 1:4 was found in 95% of women having PA antibody titer
      of 1:256 and in 99% of those with PA antibody titer of 1:512. Based on the
      relationships to measles NT antibody level, the majority of subjects with HI
      antibody titer higher than 1:8 or PA antibody level higher than 1:512 was
      reasonably assumed to be protected against clinical measles. PA seemed superior
      to HI in finding subjects with insufficient immunity against measles, because the
      former detects weak immunity more efficiently than the latter.

PMID- 18095466
TI  - [Effectiveness of newly applied infection control policies to suppress the number
      of cases with hospital-acquired influenza infection at Iwate Medical University
      Hospital--comparison of the 2004/5 and 2005/6 seasons].
AB  - Iwate Medical University Hospital (IMUH) is a general regional hospital with
      approximately 1,000 beds and emergency facilities. Due to the increased
      prevalence of cases of hospital-acquired influenza during the 2004/5 epidemic
      season, measures to systematically and comprehensively prevent the spread of
      seasonal influenza such as reinforcement of the active surveillance of influenza
      and adequacy of patient placement and the introduction of a new zoning system
      based on transmission-based precautions, were implemented. This report compares
      pre-and post intervention, and analyzes the impact on the prevalence of hospital
      acquired influenza patients. Comparison of the prevalence of the 2005/6 season
      and 2004/5 season, irrespective of the fact that patients with influenza upon
      admission to the hospital doubled from 9 patients to 18, the number of influenza
      patients assumed to have secondary infections within the hospital markedly
      decreased from 48 to 20. In the 2004/5 season, a significant correlation was seen
      between the increase in the number of community-acquired influenza infections and
      the number of hospital-acquired ones. In contrast, no significant relationship
      was seen in the 2005/6 season. To exclude any influence due to seasonal
      differences in influenza epidemics, the secondary infection rate index one showed
      a decrease from of 36.8% to 23.7%. Based on the above results, influenza measures
      at IMUH in the 2005/6 season are considered to have suppresses the number of
      secondary infections occurring within the hospital.

PMID- 18095467
TI  - [Norovirus outbreaks in a teaching hospital: the role of infection control].
AB  - In January 2004, 20 patients and 19 staff in one ward became ill in an outbreak
      of norovirus-related gastroenteritis over a 12-day period. The epidemic curve
      indicated person-to-person transmission. Infection control measures were
      instituted in consultation with the government health authorities. A prompt
      rigorous response may have prevented spread to other wards. In March 2004, 54
      staff and 1 member of a patient's family became ill in an outbreak of
      gastroenteritis. The source of norovirus contamination was associated with food
      served at the hospital restaurant. Secondary infection was prevented because the
      outbreak was recognized early and staff members with gastroenteritis symptoms
      were asked to stay home. Immediate control measures, such as identification and
      announcement of the outbreak, isolation of symptomatic individuals from others,
      personal protection, helped control the infection.

PMID- 18095468
TI  - [Profiles of intracellular expression, distribution, and activation of
      phospholipase A2 in host macrophages infected with Mycobacterium avium complex].
AB  - Our recent studies have shown that type IV cytosolic phospholipase A2 (cPLA2)
      plays an important role in the expression of macrophage (MPh) antimicrobial
      activity against the Mycobacterium avium complex (MAC). To clarify the modes of
      cPLA2 participation in MPh anti-MAC antimicrobial function in detail, we studied
      intracellular profiles of phospholilase A2, focusing on cPLA2, in MAC-infected
      MPhs, with the following findings: In murine peritoneal MPhs, cPLA2 was
      constitutively expressed even in uninfected MPhs, and MAC infection did not
      increase intramacrophage cPLA2 expression. In an RAW264.7 mouse MPh cell line
      (RAW264.7 MPhs) infected with MAC, a portion of intracellular cPLA2 was
      concentrated in MAC organisms residing within MPh phagosomes. MAC infection
      upregulated intramacrophage cPLA2 expression and induced its phosphorylation.
      These findings suggest that MAC infection of RAW264.7 MPhs may induce the
      activation of intracellular cPLA2, translocating it to phagosomes engulfing
      infected MAC organisms.

PMID- 18095469
TI  - [Isolation and identification of Helicobacter cinaedi and H. cinaedi-like
      organisms isolated from blood culture in practical laboratory procedures].
AB  - A spiral Gram-negative bacterium, Helicobacter cinaedi, has been isolated from
      clinical specimens of immunodeficient patients in Japan. We determined the
      isolation procedure and features using practical phenotypic tests for H. cinaedi
      isolated from blood culture. We applied 28 clinically isolated strains from 5
      different metropolitan institutions, whose species was reconfirmed in technical
      support at another expert veterinary medicine institute in identifying H.
      cinaedi. We also used 6 strains of type and reference. Positive signals from
      aerobic bottles in automated blood culture systems, BACTEC, were observed 4-9
      days after culture was started. A thin spread colony was found 3-4 days after the
      start of subcultures consisting of growth on 5% sheep blood agar plates with
      immediate incubation under wet and microaerophilic conditions at 35 degrees C. In
      phenotypic tests, all specimens of H. cinaedi were shown to be positive in
      nitrate reduction and to be negative in both indoxyl acetate hydrolysis and
      urease activity, underlining the usefulness of these 3 phenotypes. Tests of
      alkaline phosphatase hydrolysis, growth at different temperatures, and growth
      with 1% glycin provided additional information when referencing standard results
      of identification. We took speculative profiling data of H. cinaedi
      identification with a simple phenotypic kit, Api campy, indicating its usefulness
      in testing. These observations suggest combined methods of previously available
      tests (nitrate reduction, indoxyl acetate hydrolysis, and urease activity) with
      Api campy may be useful in differentiating H. cinaedi from H. cinaedi-like
      microorganisms when observing the characteristic thin spread colony within
      subcultures under microaerophilic conditions.

PMID- 18095470
TI  - [Detection of IgM antibody to Epstein-Barr virus, 1999-2006: analysis of data
      collected at a commercial diagnostic laboratory in Japan].
AB  - The status of infectious mononucleosis in Japanese youth has been little studied.
      To gain more information, we analyzed data from tests for Epstein-Barr virus
      specific IgM in about 180,000 serum specimens sent to a commercial diagnostic
      laboratory from clinics nationwide between 1999 and 2006. The IgM antibody to the
      viral capsid antigen (VCA) was assayed by indirect immunofluorescence with P3HR-1
      cells. In an age-distribution graph of IgM positive specimens, two peaks were
      found both in young children and youth. Boys outnumbered girls in the group of
      children aged 0 to 3, and vice versa in the group of youth aged 15 to 25. IgM
      positive specimens increased from spring to autumn only in the youth group,
      suggesting that infectious mononucleosis in this group occurs more during this
      time. Infectious mononucleosis symptoms are more severe in youth, and further
      epidemiological studies are needed to clarify the disease status in young
      Japanese adults.

PMID- 18095471
TI  - [Vibrio vulnificus pollution of imported frozen Black Tiger shrimps in Japan].
AB  - The Ariake Sea area of Japan is endemic for Vibrio vulnificus infection. V
      vulnificus was isolated from slime from tidal flats, seawater, and fish Sea year
      round as we reported previously. To identify new routes and factors of V
      vulnificus infection, we studied V. vulnificus pollution of imported frozen Black
      Tiger shrimps purchased from a fish market in Kurume, Fukuoka, Japan. V.
      vulnificus was isolated from 9 of 100 tails (9%) of Philippines products, 3 of
      100 tails (3%) of Indonesia products, and 0 out of 100 tails (0%) of Madagascar
      products. Cytotoxin-hemolysin genes were identified in 7 V. vulnificus strains
      isolated from patients with V vulnificus septicemia, 9 strains from Philippine
      products, and 3 strains from Indonesian products. These results suggest that
      imported frozen Black Tiger shrimps are a new sources of V. vulnificus infection.

PMID- 18095472
TI  - [Clinical analysis of diabetes mellitus with infectious diseases].
AB  - The frequency of diabetes mellitus has risen in Japan as the traditional diet has
      become increasing Americanized and society has aged. With this has come a rise in
      infectious diseases and complications elderly diabetic patients and a growing
      need for appropriate management to maintain their quality of life (QOL) and
      minimize medical measures. Subjects were 98 diabetic patients-60 men and 38 women
      hospitalized for intravenous antibiotic treatment of infectious disease from 2002
      to 2005. We studied plasma glucose control, plasma and urinary protein levels
      related to nephropathy, and inflammatory responses to treatment. Subjects were
      divided into good (under 6.5%), fair (from 6.5% to 8.0%), poor (over 8.0%) and
      severe (over 10%) groups by HbA1c level on admission. We then compared white
      blood cell counts, CRP levels and the antibacterial medication periods. Those
      with poorly controlled plasma glucose control, hypoalbuminuria and interrupted or
      untreated diabetes required significantly longer antibacterial administration.
      Insulin was increased by the complications of infection, and decreased as
      infection ameliorated. Appropriate antibiotic administration is essential for
      diabetic patients with infectious disease, in addition to early intervention,
      strict plasma glucose control, continuous treatment, and maintenance of good
      nutrition. Such treatment improves QOL, shortens antibiotic administration,
      staves off antibiotic-resistant bacteria, and cuts medical costs.

PMID- 18095473
TI  - [Pasteurella multocida pneumonia with molecular evidence of zoonotic
      transmission].
AB  - We report the case of a patient with pneumonia caused by Pasteurella multocida
      (P. multocida). An 83-year-old woman admitted for bronchiectasis, productive
      cough, and a high fever was found in chest radiography on admission to have a new
      infiltrative shadow in the left lower lung field. Chest computed tomography
      indicated bilateral bronchiectasis and an infiltrative lingular shadow. P.
      multocida was isolated from sputum samples. Biapenem and minocycline therapy
      ameliorated symptoms. Pulsed-field gel electrophoresis (PFGE) showed that the
      clinical isolate recovered was identical to the P. multocida isolate recovered
      from the pharyngeal swab specimen culture obtained from the patient's dog.
      Several years later, P. multocida subsp. gallicida isolates were recovered from
      human sputum and a canine pharyngeal swab specimen. PFGE confirmed these isolates
      to be identical and PFGE band patterns were identical to those of previous P.
      multocida isolates. These findings suggest that P. multocida was transmitted from
      the patient's dog to the patient and underscore the need to inform susceptible
      hosts at risk of contracting zoonotic agents about basic hygiene rules for
      keeping pets. PFGE data strengthened the evidence of zoonotic transmission of P.
      multocida through casual contact in a patient with a respiratory infection caused
      by this organism. PFGE should prove useful in both epidemiological tracing and
      preventing pasteurellosis and clarifying its pathology. Case reports of
      respiratory infections including pneumonia caused by P. multocida are increasing
      in humans, and P. multocida respiratory infections appear to occur mostly in
      patients with chronic respiratory disease. A history of pet exposure, even
      without bites or scratches, should alert the physician to P. multocida as a
      potential respiratory pathogen.

PMID- 18095474
TI  - [A case of acute bronchitis caused by Neisseria meningitidis associated with HIV
      infection].
AB  - We report the case of a patient with acute bronchitis caused by Neisseria
      meningitidis associated with HIV infection. A 36-year-old homosexual Japanese man
      being treated for HIV infection and reporting fever and a productive cough was
      found in laboratory findings to have elevated C-reactive protein but no
      leukocytosis. Chest radiography showed no infiltrates in either lung, but a
      sputum smear yielded large numbers of Gram-negative cocci, including some
      phagocytized by white blood cells. One day later N. meningitidis was reported to
      be the predominant isolate from sputum culture. The patient was diagnosed with
      acute bronchitis caused by N. meningitidis. The strain isolated from this patient
      was in serogroup B. The sequence type based on multilocus sequence typing was ST
      5583, a subtype of ST-32. This strain is resistant to penicillin G in vitro, so
      we administered tosufloxacin at 600mg b.i.d., which showed excellent efficacy.
      Because of frequent sex with many men, homosexual contact was suspected as a
      possible route of infection. Meningococcal infections apart from meningitis
      rarely are surveyed epidemiologically in Japan, and the frequency of
      meningococcal infections in general is not clear. Vigilance is needed to identify
      trends in meningococcal infection, because N. meningitidis can cause acute
      bronchitis.

PMID- 18095475
TI  - [A case of leptospirosis with pulmonary involvement].
AB  - The frequency of pulmonary involvement in leptospirosis is not well known in
      Japan. A 51-year-old man admitted with fever, bloody sputum, and general severe
      myalgia was found in laboratory studies to have thrombocytopenia, proteinuria,
      renal and liver dysfunction, and positive C-reactive protein. Chest computed
      tomography showed multiple tiny ill-defined nodules in both lungs. Intravenous
      ciprofloxacin treatment (600 mg/day) ameliorated symptoms and abnormal data.
      After starting therapy, we learned that he had been in contacted with rodents,
      and he was diagnosed with leptospirosis in a microscopic agglutination test.

PMID- 18095476
TI  - [Mental hospital outbreak of Mycobacterium tuberculosis with few copies of IS6110
      DNA fingerprinting].
AB  - We report a case of 4 patients with pulmonary tuberculosis in a mental hospital
      located in Yamanashi, Japan, between 2000 and 2004 in which 3 isolates of
      Mycobacterium tuberculosis were analyzed using IS6110 restriction fragment length
      polymorphism (RFLP). DNA fingerprinting showed them to be identical and the copy
      number to be two. Additional RFLP using (CGG)5 fingerprinting yielded the same
      result and a copy number of 15, suggesting a M. tuberculosis outbreak. (CGG)5
      analysis thus proved useful in supplementary typing method like polymorphic G-C
      rich repetitive sequence (PGRS) or spoligotyping.

PMID- 18095478
TI  - [ELISA kit in outbreaks of infectious gastroenteritis among elderly nursing
      home].

PMID- 18095477
TI  - [A case of sepsis caused by Enterobacter cloacae producing both type SHV-12 and
      type CTX-M-14 ESBLs in a post bone-marrow transplantation patient].
AB  - Third-generation cephalosporin-resistant Enterobacter cloacae was isolated from
      the blood culture of a 31-year-old woman after bone-marrow transplantation. Since
      this strain was resistant to third-generation cephalosporins, the production of
      extended-spectrum beta-lactamases (ESBLs) was suspected. PCR and a sequence
      analysis confirmed two ESBL genes, bla(SHV-12) and bla(CTX-M-14). No bacteria
      were detected after meropenem was administered, and symptoms abated. This is, to
      our knowledge, the first report in Japan of E. cloacae clinical isolates
      simultaneously producing both SHV-12 and CTX-M-14 ESBL. In cases where
      chromosomal AmpC over-production of E. cloacae concomitantly produces ESBL,
      caution should be exercised due to the potential development of resistance
      against extended-spectrum beta-lactam agents.

PMID- 18095479
TI  - [Differences in vocalization and morphology of the syrinx between Carrion crows
      (Corvus corone) and Jungle crows (C. macrorhynchos)].
AB  - The vocal characteristics and the morph of the syrinx in Carrion crows (Corvus
      corone) and those in Jungle crows (C. macrorhynchos) were compared. The
      vocalizations of both species of crow were recorded into sonograms and analyzed.
      The appearance and inner configuration of the syrinx were observed using
      stereoscopic microscope. In addition, the inside diameter of the syrinx, the
      sizes of the labia and the attached position of the syringeal muscles were
      measured. The attached figures of syringeal muscles were different between the
      two species. The vocalizations of Carrion crows were noisier than possibly
      because their labias were noticeably smaller than those of Jungle crows. The
      attachment patterns of the syringeal muscles in Jungle crows suggested that they
      allow for more flexibility on the inside structure of the syrinx. The inner space
      of the syrinx in Jungle crows was also wider than those of Carrion crows. These
      results suggested that Jungle crows may be able to make various vocalizations
      because of these morphological characteristics.

PMID- 18095480
TI  - [Anatomical names of skeletal surfaces: analysis and classification of Latin
      names, and comparison with corresponding Japanese names].
AB  - For better understanding of the structures comprising the human body and in view
      of possible need for future revision, Latin anatomical names (Terminologia
      Anatomica) of the skeletal surfaces were analyzed and classified, and compared
      with the corresponding Japanese anatomical names. The words following Facies
      indicated: 1) morphological resemblance of the surface; 2) the structure that
      articulates with the surface; 3) the structure attached to the surface; 4) the
      structure in contact with the surface; 5) the way of connection between the
      surface and the structure that faces it; 6) the structure of which the surface is
      a component; 7) the structure that the surface faces; 8) the site that the
      surface faces; 9) the relative position of the surface; 10) the non-relative
      position of the surface; 11) an articulation of the surface; or 12) both the
      structure with which the surface articulates and the structure of which the
      surface is a component. Analysis of Latin names and comparison with Japanese
      names clarified some characteristics of both names and revealed some problems in
      them.

PMID- 18095481
TI  - [Multiple functions of glutamate transporter EAAC1 in motor neurons].
AB  - The neuronal glutamate transporter EAAC1 localizes on neuronal cell membrane and
      uptakes glutamate from extracellular space. This function is crucial for the
      termination of glutamate-mediated signaling in synapse and also for prevention of
      neuronal death by suppressing glutamate toxicity. However, the possible mechanism
      of EAAC1 in preventing neuron death had not been resolved as compared with glial
      glutamate transporters such as GLT-1. Recently some groups revealed its
      additional mechanisms in terms of neuronal protection. In this review we
      introduce a unique "rescue" function of EAAC1, which is independent of clearance
      of extracellular glutamate. We recently identified that the decreased expression
      of EAAC1 following nerve injury in motor neuron was observed in mouse but not in
      rat, and the suppression in mouse was associated with motor neuron death seen in
      the mouse. This phenomenon leaded us to identification of a novel mechanism
      underlying the neuronal protection of EAAC1. During apoptotic stimuli, a
      mitochondrial protein, holocytochrome-c synthetase (HCCS) translocates to outside
      the mitochondria, binds to, and suppresses the X-linked inhibitor of apoptosis
      protein (XIAP), leading to activation of caspase-3. The N-terminus of EAAC1 can
      bind to HCCS, which interferes with the HCCS-XIAP association, and thereby
      maintain XIAP activity. This unique anti-apoptotic mechanism of EAAC1 functions
      in rescuing motor neurons from NGF deprivation and nerve injury. These facts
      imply that the EAAC1 has multiple mechanisms in prevention of neuron death.

PMID- 18095482
TI  - [FGF-2-treatment improves locomotor function via axonal regeneration in the
      transected rat spinal cord].
AB  - The failure of axonal regeneration after central nervous system (CNS) injury is
      thought to be due in part to the expression of molecules inhibitory for axonal
      growth and/or the lack of neurotrophic factors. Antibody treatment to neutralize
      axon growth inhibitory activity, and delivery of neurotrophic factor have been
      attempted extensively to overcome inhibition and augment regeneration of spinal
      motor pathways. Local delivery of neurotrophins can counteract pathological
      events and induce a regenerative response after both acute and chronic spinal
      cord injury. Furthermore, genetically modified cells that deliver neurotrophins,
      olfactory ensheathing glia that facilitate nerve regeneration and neural
      stem/progenitor cells that generate neurons or glia have been studied. These
      experiments result in a substantial level of restoration of motor function, and
      give evidence for possible regeneration of particular CNS axons related
      locomotion activity. However, more practical and promising methods to induce more
      drastic axonal regeneration are desired at present for clinical use. Fibroblast
      growth factors (FGFs) have been implicated in numerous cellular processes. FGF-2
      stimulates the growth of blood vessels via proliferation of endotherial cells and
      smooth muscle cells, and enhances neurogenesis via mitotic activity of neural
      stem/progenitor cells. As angiogenesis is crucial for forming nervous system, FGF
      2 may play roles for nerve regeneration in the injured spinal cord. We examined
      the effects on locomotor function of the FGF-2 injected into the completely
      transected rat spinal cord. The locomotor function of the FGF-2-treated animals
      was substantially recovered up to extent where the joint of the hind limb moves 6
      weeks after transection, but the recovery was not seen at all on the locomotor
      activity of the vehicle-treated animals. This regeneration might be facilitated
      by prominant cell growth of fibroblast-like cells markedly enhanced by FGF-2
      around the lesion site, because the cells have properties advantageous for
      neurite outgrowth. FGF-2-induced cells may become a crucial and promising tool to
      attain successful axonal regeneration.

PMID- 18095483
TI  - [In vivo characterization of sonic hedgehog in the peripheral nerve
      regeneration].
AB  - A large number of genes regulate the process of regeneration after the nerve
      injury. Facial nerve axotomy of rats provides us with a useful model in which to
      study the molecular and cellular mechanisms of peripheral nerve regeneration. We
      performed the subtracted library screening of the facial nucleus after the facial
      nerve axotomy. We identified the sonic hedgehog (Shh) as a candidate molecule
      that regulates regeneration of injured neurons. By making adenoviral vector that
      transfers Shh, we found that the motor neuron survival was significantly promoted
      for 3-5 days after neonate rat injury. Furthermore, the continuous application of
      cyclopamin, which is a signal inhibitor of Smoothened, to the injured site, motor
      neuron death was induced in the adult rats after axotomy. These results indicate
      that Shh may play a regulatory role in the regeneration after nerve injury.

PMID- 18095484
TI  - [Molecular mechanism and regulation of axon growth inhibition].
AB  - In the adult mammalian central nervous system (CNS), it is well known that
      injured axons exhibit very limited regeneration ability. Due to this lack of
      appropriate axonal regeneration, a traumatic damage to the adult brain and spinal
      cord frequently causes permanent neuronal deficits such as paralysis. Several
      axon growth inhibitors, including myelin-associated glycoprotein, Nogo, and
      oligodensrocyte myelin glycoprotein, in the CNS have been identified in the
      myelin. Receptor complex comprising of the Nogo receptor, the p75 receptor, and
      LINGO-1 transduces the signals from all of these inhibitors in vitro. Downstream
      of these inhibitors, activation of small GTPase RhoA and its effector Rho-kinase
      has been shown to be a key element for neurite growth inhibition and growth cone
      collapse elicited by these inhibitors. Consistent with these findings in vitro,
      inhibition of RhoA or Rho-kinase in vivo promotes axon growth and functional
      recovery after spinal cord injury. Recently, several developmental guidance
      proteins, including repulsive guidance molecules, semaphorin, and ephrin are
      suggested to be involved in axon growth inhibition after injury to the CNS. Thus,
      multiple axon growth inhibitors seem to contribute to inability of the injured
      axons to regenerate, and therapeutic strategy to block the multiple axon growth
      inhibitors may provide efficient tools that produce functional regeneration
      following injuries to the CNS. In addition, it is noted that synaptic plasticity
      in pre-existing pathways and the formation of new circuits through collateral
      sprouting of lesioned and unlesioned fibers are important components of the
      spontaneous recovery process. The molecular mechanism of this phenomenon is
      poorly understood, and elucidation of this will contribute to enhancement of
      functional recovery after incomplete injury to the CNS. I will summarize recent
      findings regarding these issues.

PMID- 18095485
TI  - [Immune reconstitution inflammatory syndrome in the central nervous system].
AB  - The prognosis of HIV-related disorders have markedly improved after highly active
      antiretroviral therapy was introduced, however, following initiation of the
      therapy, some patients with severe immunodeficiency develop a paradoxical
      clinical deterioration despite decreased HIV viral load and increased CD4+ T-cell
      counts. These phenomena are recently recognized as immune reconstitution
      inflammatory syndrome (IRIS). It is considered that the rapid restoration of the
      immune system leads to exuberant inflammatory responses to antigenic stimuli.
      Although the disorders are sometimes life-threatening, the definition and the
      management of IRIS have not been established yet. We review the current knowledge
      of IRIS, especially in the area of HIV-related CNS disorders. Cryptococcal
      meningitis and progressive multifocal leukoencephalopathy (PML) are common
      disorders which cause CNS IRIS. HIV encephalopathy is also reported to develope
      IRIS. Infiltration of cytotoxic CD8+ T lymphocytes is observed in the suffered
      brain tissue of PML and HIV encephalopathy, and it may be one of the pathogenic
      factors.

PMID- 18095486
TI  - [A case of direct carotid cavernous fistula, whom three-dimensional computed
      tomographic angiography was helpful for decision making of selective coil
      embolization].
AB  - We reported the case of an 84-year-old female suffering from chemosis and
      exophthalmos. Carotid arteriograms revealed a direct carotid-cavernous fistula
      (CCF) but could not clearly show the fistula point because of its high-flow
      nature. We then performed three-dimensional computed tomographic angiography (3D
      CTA) using a multi detector-row CT (MDCT) scanner. Multi-planar reformatted CT
      images distinctly revealed a right carotid aneurysm at the cavernous portion and
      a shunting point between the aneurysm and the cavernous sinus. Based on this
      information, we opted to performa transvenous coil embolization to treat this
      patient. Successful selective coil embolization was performed at the fistulous
      point was done with a smaller number of coils than ordinarily required in sinus
      packing. Performing 3D-CTA by using a MDCT was helpful in decision making for the
      selective coil embolization to treat direct CCF.

PMID- 18095487
TI  - [Rapid disappearance of acute epidural hematoma by percutaneous aspiration of
      subperiosteal hematoma--case report].
AB  - We present the case of an 8-year-old boy who was injured in a bicycle accident
      and was admitted with a right frontal skull fracture, an acute epidural hematoma,
      a right frontal laceration, and a subperiosteal hematoma on admission. After the
      frontal cutaneous suture, the subperiosteal hematoma was aspirated by the
      percutaneous needle. Two hours later, a CT scan revealed that the epidural
      hematoma was disappeared. It is speculated that the subperiosteal and epidural
      hematoma communicated via the skull fracture thus necessitating the evacuation of
      the epidural hematoma by subperiosteal aspiration.

PMID- 18095488
TI  - [A small cortical infarction showing dysarthria and left hypoglossal paresis].
AB  - We reported the case of a 77-year-old female who presented with left hypoglossal
      paresis and dysarthria due to a small cortical infarction. She was admitted to
      our hospital because of the sudden onset of dysarthria. A neurological
      examination revealed deviation of the tongue to the left and paretic dysarthria
      without motor paralysis in the extremities. Diffusion-weighted imaging of the
      brain revealed a slightly high signal intensity at the right precentral gyrus,
      indicating an acute brain infarction in the motor cortex. Carotid MR angiography
      revealed atherosclerotic changes seen at the right internal carotid artery,
      suggesting an atherothrombotic brain infarction with artery-to-artery embolism.
      The patient was discharged on the 17th day of hospitalization with slight left
      hypoglossal paresis. Isolated cranial nerve paresis is a rare symptom in stroke
      patients. Furthermore, in this patient, dysarthria in this case was more obvious
      than that of peripheral hypoglossal palsy. Recent electrophysiological has
      investigation indicates that the corticolingual tract plays a significant role in
      the presence of pure dysarthria in the stroke patients. This case indicate that
      cortical infarction in the primary motor cortex may produce isolated hypoglossal
      nerve paresis and dysarthria due to disruption of the corticolingual tract.

PMID- 18095489
TI  - [Endarterectomy for cervical internal carotid artery stenosis accompanied with
      severe aortic valve stenosis--case report].
AB  - A 75-year-old man, who had undergone coronary artery bypass graft and repair for
      abdominal aortic aneurysm, suffered from angina pectoris due to severe aortic
      valve stenosis complicated with asymptomatic bilateral cervical internal carotid
      artery stenoses. Brain perfusion imaging revealed reduced cerebral blood flow and
      cerebrovascular reactivity to acetazolamide in the bilateral cerebral
      hemispheres. First, the patient underwent left carotid endarterectomy, and the
      postoperative course was uneventful. Postoperative brain perfusion imaging showed
      improvement of cerebrovascular reactivity to acetazolamide in the bilateral
      cerebral hemispheres. Seven weeks later, the patient underwent aortic valve
      replacement, and his postoperative course was uneventful. Carotid endarterectomy
      rather than carotid artery stenting should be preceded for cervical carotid
      stenosis complicated with severe aortic valve stenosis.

PMID- 18095490
TI  - [A case of meningeal carcinomatosis presenting with bilateral hearing loss].
AB  - We report the case of a 63-year-old male who developed rapidly progressive
      bilateral deafness. Two months later he became stuporous, and was transferred to
      our hospital. The patient's MRI demonstrated bilateral hypertrophic VII-VIII
      cranial nerve roots that were well enhanced. Gradually, the patient's condition
      worsened, and he died on the 12th day after admission. Autopsy revealed meningeal
      carcinomatosis with poorly differentiated gastric adenocarcinoma. White firm
      masses of the bilateral seventh and eighth bilateral cranial nerve roots were
      found at autopsy, which were found to be metastases of the gastric cancer cells
      as well. Metastatic tumors can be take into consideration as a differential
      diagnosis for bilateral-enhanced eighth cranial nerve root masses.

PMID- 18095491
TI  - [Homonymous visual field defect due to optic tract involvement in a patient with
      multiple sclerosis].

PMID- 18095492
TI  - [An autopsy case of peripheral neuropathy, complicated by status eplilepticus,
      associated with high titer of anti-VGKC antibodies].

PMID- 18095493
TI  - [Giovanni Alfonso Borelli: "De Motu Animalium" (1680-1681)].

PMID- 18095494
TI  - [Non-herpetic acute limbic encephalitis-like manifestation in a case of
      Hashimoto's encephalopathy with positive autoantibodies against ionotropic
      glutamate receptor epsilon2].
AB  - A 37-year-old woman developed memory disturbance and seizures preceded by
      headache and high fever. Physical examination revealed persistent high fever,
      confusion, neck stiffness, anterograde and retrograde amnesia and disorientation.
      CSF showed pleocytosis and normal glucose level, and negative herpes simplex
      virus DNA on PCR. The fluid attenuated inversion recovery (FLAIR) MRI of the
      brain demonstrated nearly symmetric high signal intensity areas in the bilateral
      mesial temporal lobes. The tentative clinical diagnosis was non-herpetic acute
      limbic encephalitis (NHALE), and administration of methylprednisolone improved
      her conditions. Laboratory tests revealed mild hypothyroidism with high titers of
      serum antibodies against TPO and thyroglobulin, consistent with Hashimoto's
      disease. In addition, antibodies against amino terminal of alpha-enolase in the
      serum and those against glutamate receptor (GluR) epsilon2 in the serum and CSF
      were positive. A final diagnosis of Hashimoto's encephalopathy associated with
      GluRepsilon2 antibody was made. The present case suggests that NHALE-like
      clinical manifestation can be produced by autoimmune-mediated encephalopathies.

PMID- 18095495
TI  - [Case of thrombotic thrombocytopenic purpura associated with clopidogrel].
AB  - We reported a Japanese first case of thrombotic thrombocytopenic purpura (TTP)
      induced by clopidogrel, a newly developed antithrombotic drug, marketed in May
      2006 in Japan. This 80 years old woman developed cerebral infarction and suffered
      from Broca's aphasia and right hemiparesis. Clopidogrel was started on Day 6
      after the onset. On Day 10, four days after the administration of clopidogrel,
      two egg-sized purpura with marked decrease in platelet count was found. The
      purpura extended over the entire body in next few days. Despite total seven times
      of plasma exchange, platelet count did not normalize. Twenty four days after the
      onset of TTP, the patient developed central catheter infection and died of
      sepsis. TTP will become a lethal side effect of clopidogrel, when diagnosis and
      treatment are late. Because it is assumed that the mechanism of clopidogrel
      induced TTP differs from that of ticlopidine, we should establish firm treatment
      urgently.

PMID- 18095496
TI  - [Case of adult influenza type A virus-associated encephalopathy successfully
      treated with primary multidisciplinary treatments].
AB  - The patient in this study was a 43-year-old woman who had become unconscious
      after contracting influenza virus type A infection. Brain CT showed severe brain
      swelling. Brain MRI also showed brain edema with no specific abnormality on T2
      weighted images. We diagnosed her as having influenza type A virus-associated
      encephalopahty and treated her with Oseltamivir, methylprednisolone pulse
      therapy, and a high dose of intravenous immunoglobulins. In addition, we treated
      her with hypothermia and a high dose of intravenous ATIII because of the severe
      brain swelling and possibility of DIC. After the treatments, brain swelling had
      improved, and she regained consciousness without any sequelae. Adult influenza
      virus-associated encephalopathy is rare. We were able to successfully treat our
      patient with primary multidisciplinary treatments without causing sequelae.

PMID- 18095497
TI  - [Patient with innominate artery steal accompanied with cerebral infarction].
AB  - A 49-year-old man suddenly suffered left hemiplegia, and was brought to our
      hospital by ambulance at the beginning of August, 2006. He had a history of
      hypertension, and had received replacement of a synthetic graft in the ascending
      aorta and aortic arch with innominate artery for dissecting aneurysm in the aorta
      2 years before. On diffusion-weighted magnetic resonance images obtained after
      admission, cerebral infarction was detected at the right corona radiata, and MR
      angiography (MRA) showed obstruction of the right middle cerebral artery. He was
      given intravenous tissue-plasminogen activator (t-PA) a few hours after arrival,
      and his hemiplegia was improved on the following day. At 11 days after onset,
      recanalization of the right middle cerebral artery was seen by MRA. On Doppler
      ultrasonographic examination, obstruction and thrombus in the innominate artery
      were observed. Retrograde flow of the right vertebral artery was demonstrated by
      both pulse-Doppler ultrasonography and velocity-coded color MRA. This patient is
      a rare example of innominate artery steal and ischemic cerebrovascular disease
      with obstruction of the innominate artery. Cerebral infarction in this patient
      might have developed via artery-to-artery embolism, with the thrombus in the
      innominate artery, rather than through a hemodynamic mechanism with innominate
      artery steal.

PMID- 18095499
TI  - [Case of baroreflex failure after bilateral revascularization of the cervical
      carotid artery].
AB  - We report a patient of baroreflex failure two years after bilateral cervical
      internal carotid artery (ICA) revascularization. A 76-year-old hypertensive man
      was admitted to our hospital after suffering multiple syncopal events for the
      past 2 years prior to admission. He received bilateral surgical and endovascular
      revascularization for stenotic lesions of the ICA orifices 4 years ago.
      Intervention consisted of carotid endarterectomy and carotid stenting for the
      right and left ICAs, respectively. Head T2-weighted magnetic resonance images
      demonstrated multiple high intensity signals in the basal ganglia bilaterally. To
      investigate his autonomic function, head-up tilt test, 24-hour ambulatory blood
      pressure measurements, and Valsalva's maneuver were performed. The patient
      demonstrated marked orthostatic hypotension without increment of heart rate,
      increased variability of blood pressure and abnormal hypertensive surges in a
      single 24 hour period, and abnormal response of heart rate during Valsalva's
      maneuver. These findings were indicative of impaired baroreflex-mediated
      vasomotor and heart rate control. Other examinations involving hematological
      analysis, cardiac function assessment, and scintigraphy for pheochromocytoma were
      within normal limits except for a marked increase in plasma norepinephrine during
      hypertensive surge. We therefore considered that he had baroreflex failure
      resulting from previous bilateral ICA orifice revascularization. The patient was
      given diazepam during hospitalization. After then, his blood pressure stabilized
      somewhat and syncopal attacks were controlled. Our case suggests that patients,
      who undergo bilateral ICA orifice revascularization and present with syncopal
      attacks, should be considered baroreflex failure even if the patient is post
      operative several years. Long-term follow up should therefore be necessitated in
      patients who undergo bilateral carotid revascularization.

PMID- 18095500
TI  - [Case of Isaacs' syndrome associated with Hashimoto disease].
AB  - We report a case of Isaacs' syndrome associated with Hashimoto disease. A 26-year
      old woman, who had a past history of Hashimoto disease, complained of involuntary
      movements and muscle cramp in lower extremities. On examination, myokymia was
      seen in lower extremities. Myokymia was observed even during sleep, and worsened
      by exercise or bathing. The antibody against voltage-gated potassium channel
      (VGKC) was positive. Myokymic discharges were recorded with needle EMG in lower
      extremities. The patient was diagnosed as having Isaacs' syndrome. Isaacs'
      syndrome tends to be associated with some other autoimmune diseases. We discussed
      the correlation between Isaacs' syndrome and autoimmune disease. About 23% of
      Isaacs' syndrome cases are associated with some other autoimmune diseases and
      myasthenia gravis was most common. This is the first case report of Isaacs'
      syndrome associated with Hashimoto disease in Japan.

PMID- 18095498
TI  - [Case of highly active anti-retroviral therapy-induced immune reconstitution
      inflammatory syndrome in AIDS-related progressive multifocal
      leukoencephalopathy].
AB  - A 44-year-old man presented with difficulties in gripping a ball with the left
      hand upon playing tennis. He developed muscle weakness involving the left limbs,
      as well as memory decline, with subsequent gradual worsening of such symptoms.
      Cranial MRI showed multiple high intensity lesions in the white matter on T2
      weighted imaging and FLAIR imaging. Serologic testing was positive for HIV
      infection and laboratory studies revealed a CD4+T cell count of 103 cells/microl
      and a plasma HIV-1 RNA load of 240,000 copies/ml. Accordingly, the diagnosis of
      AIDS was made. Although the initial result of DNA amplification by PCR for
      detection of the JC virus with CSF was negative, PML was suspected because of the
      presence of multifocal white matter lesions. Four weeks after the commencement of
      highly active anti-retroviral therapy (HAART), the HIV-1 RNA load was decreased
      from 680,000 to 480 copies/ml, although the CD4+T cell count was unchanged. JC
      virus DNA became positive at the second examination. Five weeks after the
      commencement of HAART, general fever, disturbance of consciousness, and brain
      edema suddenly developed, and the patient died within two days. Histological
      examination of the autopsied brain revealed demyelination and reactive gliosis
      within the white matter and JC virus antigen was detected in oligodendrocytes,
      consistent with a diagnosis of PML. The most striking feature was an intense
      perivascular infiltration by CD8+T cells with proteinaceous fluid exudation,
      suggesting an occurrence of HAART-induced immune reconstitution inflammatory
      syndrome. Immune reconstitution inflammatory syndrome should be considered as a
      fatal complication of HAART in patients with AIDS-related PML.

PMID- 18095501
TI  - [Recurrent bacterial meningitis in a case of Crouzon syndrome after craniofacial
      surgery].
AB  - A 29-year-old woman, who was diagnosed as Crouzon syndrome for which two cranio
      facial surgeries had been performed as a child and at the age of 19, developed
      high fever, headache, and confusion for two days. She was admitted to our
      hospital. She was diagnosed as bacterial meningitis by cerebrospinal fluid
      examinations, and her condition was immediately improved by antibiotics. At the
      age of 23, she also suffered from bacterial meningitis caused by otitis media and
      sinusitis, and recovered by antibiotics with no sequela. Her cranial computed
      tomography showed sphenoid and ethmoid sinusitis, and bone deformation and
      hypertrophy with no fistula connecting intracranial space and sinus. Dead space
      by cranio-facial surgeries might cause the development of chronic or recurrent
      sinusitis leading to bacterial meningitis. Our patient is the second case of
      recurrent bacterial meningitis with Crouzon syndrome to our knowledge. We should
      recognize that recurrent sinusitis with Crouzon syndrome after cranio-facial
      surgery is a risk of recurrent meningitis.

PMID- 18095502
TI  - [Videofluorographic evaluation of dysphagia in a patient with myasthenia gravis].
AB  - A 64-year-old woman with myasthenia gravis (MG) presented with isolated bulbar
      symptoms. Two years earlier, she had developed neck weakness, diplopia, and
      ptosis and was diagnosed with MG. Extensive thymectomy was performed, and she was
      treated with predonisolone (PSL). The neck weakness, diplopia, and ptosis
      improved over a 2-year period. However, dysphagia developed, and her voice took
      on a nasal tone that did not improve subjectively even after administration of 10
      mg of edrophonium chloride (EC). We then performed videofluorography (VF). After
      consumption of 10 ml of liquid barium and 8 g of corned beef hash, she attempted
      to swallow, but the residue remained in the valleculae and the piriform fossa.
      After the EC injection, her dysphagia on ingestion of corned beef hash improved;
      however, there was slight subjective improvement in swallowing. Drinking of
      liquid barium resulted in some residue with slight improvement of dysphagia.
      After treatment with 70 mg of PSL for 4 weeks, VF showed improvement of
      dysphagia. Thus, VF, particularly during consumption of solid food, with EC
      administration is helpful in evaluating bulbar symptoms in patients with MG.

PMID- 18095503
TI  - [Probable amebic brain abscess in a homosexual man with an Entamoeba histolytica
      liver abscess].
AB  - A 51-year-old Japanese-Brazilian homosexual man was admitted to a hospital
      because of fever, headache and right epigastralgia. He had been homosexual for 20
      years. An abdominal CT revealed a liver abscess and microscopic examination of
      the pus of the drainage revealed cystic forms of Entamoeba histolytica. Oral
      administration of metronidazole 2,250 mg/day was started for amebic liver
      abscess. He complained of severe throbbing headache, and magnetic resonance
      imaging (MRI) of the brain showed a brain mass of approximately 2 cm in diameter
      in the right parietooccipital lobe. An amebic brain abscess was suspected and he
      was transferred to our hospital. Continuous oral administration of metronidazole
      for 49 days instead of invasive procedures gradually improved headache, fever and
      right epigastralgia. On the follow-up MRIs, the brain mass was gradually
      encapsulated, reduced its size, and finally disappeared. A diagnosis of amebic
      brain abscess was made on the basis of coexistent amebic liver abscess, MRI
      findings and a dramatic effectiveness to metronidazole. One should pay attention
      to E. Histolytica infection in the differential diagnosis of the abscess of the
      liver and brain since it has been increasing in Japan in recent years.

PMID- 18095504
TI  - Recommendations for post-discharge patient follow up after cardiac valve
      interventions: a position paper.

PMID- 18095505
TI  - Floppy mitral valve/mitral valve prolapse and genetics.
AB  - Mitral valve prolapse (MVP) is a defect in the mitral valve where a redundancy of
      valve tissue is associated with a variety of clinical expressions, ranging from
      an isolated mild bulging of the mitral valve to a severe prolapse of the mitral
      valve with extensive mitral regurgitation. As the natural history and
      complications of MVP are not always benign, it seems essential to strive for the
      proper management of these patients. The identification of functionally related
      genes could provide helpful clues and increase the present understanding of the
      pathogenesis of MVP, with the ultimate goal of developing targeted therapies. The
      genetics of MVP can be divided into two parts: (i) Genetics in floppy mitral
      valve/MVP; and (ii) genetics in heritable connective tissue disorders (Marfan
      syndrome, polycystic kidney, etc.) associated with floppy mitral valve. Herein,
      the known genetic aspects of MVP are described, according to the above-mentioned
      scheme.

PMID- 18095506
TI  - Echocardiography-guided balloon mitral valvotomy: transesophageal
      echocardiography versus intracardiac echocardiography.
AB  - BACKGROUND AND AIM OF THE STUDY: Although balloon mitral valvotomy (BMV) can be
      guided by on-line transesophageal echocardiography (TEE) or intracardiac
      echocardiography, few reports have been made comparing these methods. The study
      aim was to compare on-line TEE and on-line intracardiac echocardiography in the
      guidance of BMV. METHODS: Fifty-five consecutive patients with significant mitral
      stenosis (mitral area < or = 1.5 cm2), but without significant mitral
      regurgitation (< or = Sellers grade 2) or left atrial cavitary thrombus,
      underwent BMV. Patients were prospectively randomized to two groups: group A (n =
      28) received on-line guidance by multiplane TEE, while group B (n = 27) received
      on-line guidance by intracardiac echocardiography. Pre-procedural and post
      procedural data were compared between these groups. RESULTS: There were no
      significant differences in baseline data and procedural outcomes. On-line TEE was
      found to be of great help for septal puncture, immediate assessment of results,
      and the prevention and detection of complications. On-line intracardiac
      echocardiography also aided in septal puncture and was better tolerated by
      patients, but had less imaging capabilities, was more expensive, required a
      second venous access, and on occasion interfered with manipulation of the
      puncture and balloon catheters. CONCLUSION: Although both TEE and intracardiac
      echocardiography were safe and effective for on-line guidance of BMV, TEE
      provided better imaging capabilities.

PMID- 18095507
TI  - Configurations of the mitral valve during off-pump coronary artery bypass
      grafting: endoscopic and three-dimensional analysis.
AB  - BACKGROUND AND AIM OF THE STUDY: During off-pump coronary artery bypass grafting
      (CABG), mitral regurgitation (MR) has been experienced in relation to the
      procedures. The study aim was to evaluate the mitral valve configuration, with
      particular focus on annular behavior, during off-pump CABG, using cardiac
      endoscopy and digital 3-D ultrasound sonomicrometry. METHODS: Following
      implantation of six crystals of the digital 3-D ultrasound sonomicrometer around
      the mitral annulus, and two crystals on the epicardial base of the papillary
      muscles, off-pump CABG was simulated in seven beagle dogs. The heart was perfused
      with pellucid Krebs-Henseleit solution in situ, with controlled left ventricular
      end-diastolic pressure (LVEDP). The behaviors of the mitral annulus and leaflets
      were then observed endoscopically with only cardiac displacement, 15 min
      occlusion of the left anterior descending artery (LAD), or 15 min occlusion of
      the left circumflex artery (LCx) with cardiac displacement. Dimensions between
      the crystals were also recorded using digital 3-D ultrasound sonomicrometry.
      RESULTS: With only cardiac displacement, no MR was observed endoscopically, and
      no major changes occurred in annular configuration when coronary perfusion was
      maintained. In one dog, MR was observed only from the anterolateral site after
      LAD occlusion. MR from the posteromedial site was observed by occlusion of the
      LCx in all cases, with significant (p < 0.01) enlargement of the mitral annular
      dimensions. CONCLUSION: Cardiac displacement alone did not cause MR if coronary
      perfusion was maintained. Occlusion of the LAD rarely caused MR from the
      anterolateral site, whereas occlusion of the LCx normally caused MR from the
      posteromedial site; the posteromedial annulus was enlarged, even when the LVEDP
      was controlled.

PMID- 18095508
TI  - Anomalous papillary muscle causing tethering of the mitral valve.
AB  - Herein is described a rare case of anomalous papillary muscle (APM) insertion
      which caused severe mitral regurgitation (MR). In this case, the anterolateral
      papillary muscle inserted directly into the left ventricular surface of the
      anterior mitral leaflet (AML), without an intervening chorda. The APM pulled the
      AML down towards the left ventricle, causing a marked tethering of the mitral
      valve. The dilatation and dysfunction of the left ventricle exacerbated the
      tethering of the mitral valve, which eventually caused severe MR. At surgery,
      after resection of the APM, the mitral valve was replaced with a prosthetic
      valve. A directly inserting APM, which is known as a rare cause of a left
      ventricular outflow tract obstruction, seems to transmit a stronger tethering
      force to the mitral leaflet than does a normal stay chorda. Thus, the present
      case shows that this type of APM might cause MR due to a mechanism of valve
      tethering.

PMID- 18095509
TI  - Surgery for infective endocarditis on mitral annulus calcification.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the characteristics
      of bacterial endocarditis complicating mitral annulus calcification, and to
      evaluate the surgical results. METHODS: Twenty-four patients (mean age 64 years)
      underwent surgery for mitral insufficiency secondary to mitral endocarditis with
      annulus calcification (acute, n = 18; healed, n = 6). Surgery was performed as an
      emergency in seven cases for septic (n = 3) or cardiogenic (n = 4) shock. An
      aortic prosthesis had previously been placed in three cases. Comorbidities noted
      included chronic renal insufficiency/dialysis (n = 8), cancer (n = 6), coronary
      disease (n = 6), and obstructive cardiomyopathy (n = 1). Nine patients suffered
      an embolic complication, such as stroke (n = 7, of which three had coma), splenic
      (n = 3), or lower limb (n = 1). The microorganism present was identified as
      Staphylococcus aureus (n = 9), Streptococcus/ Enterococcus sp. (n = 12), or
      others (n = 3). The left atrial diameter was 48 mm, the ejection fraction 63%,
      and the septal thickness 13 mm. RESULTS: The mean severity score of annulus
      calcifications (range: 1 to 5) was 1.9. The anatomical lesions included:
      vegetations (n = 16, of which eight were > 10 mm), leaflet perforation (n = 9),
      chordae rupture (n = 9), aortic abscess (n = 2) and mitral annular abscess (n =
      9), and one fistulation into the pericardium. The valve was repaired in 15 cases,
      and replaced in nine (seven bioprostheses, two mechanical). Associated procedures
      included aortic valve replacement (n = 7) and coronary artery bypass (n = 3). The
      in-hospital mortality was 29% (n = 7); all patients who died were operated on
      during the acute phase. All patients who presented with septic shock or coma
      died. After a mean follow up of 46 months, six patients had died (overall
      survival was 46% at 33 months), and 11 were in NYHA class I/II. One recurrence of
      endocarditis was treated medically. CONCLUSION: Bacterial endocarditis
      complicating mitral annulus calcification has a poor prognosis due to the
      frequent comorbidity and severity of the infectious complications. Patients in
      septic shock or coma do not appear to be suitable candidates for surgery. Valve
      repair was possible in two-thirds of the present patients; otherwise, a
      bioprosthetic replacement was the option of choice.

PMID- 18095510
TI  - The risk of valve surgery for endocarditis in patients with dialysis-dependent
      renal failure.
AB  - BACKGROUND AND AIM OF THE STUDY: Valvular endocarditis occurring in patients with
      dialysis-dependent renal failure increases the risk of mortality following valve
      surgery, but few specific data are available to guide surgical selection. The
      study aim was to develop a simple risk scoring system to identify high-risk
      dialysis patients undergoing valve surgery for endocarditis. METHODS: Using STS
      data from between January 1994 and December 2003, a total of 1,862 valvular
      procedures was recorded in dialysis patients with endocarditis. Isolated mitral
      procedures were performed in 718 patients, isolated aortic in 656, double valves
      in 386, isolated tricuspid in 55, and triple valves in 47. Logistic regression
      analysis was performed relating baseline variables to hospital mortality. Points
      were assigned to each significant risk factor by rounding regression coefficients
      to integers. An estimate of risk was obtained for each patient by averaging the
      predicted mortality among all patients having the same number of total points.
      RESULTS: In the logistic regression, significant variables (all p < 0.001) and
      effect estimates (odds ratios; points) were: cardiogenic shock or salvage status
      (2.77; 3), double valve (2.37; 3), age > or = 60 years (2.02; 2), isolated mitral
      valve (1.89; 2), body surface area > 2.1 m2 (1.86; 2), arrhythmia (1.56; 1),
      active endocarditis (1.54; 1), and female gender (1.53; 1), with a C-statistic of
      0.705. Mortality increased exponentially as a function of points, with operative
      mortality exceeding 70% at 10 points. CONCLUSION: The risk of mortality for
      dialysis patients having valve surgery for endocarditis is high, yet depends on a
      variety of factors. The proposed risk scoring system successfully discriminates
      between higher and lower risk patients, and could contribute to better decision
      making.

PMID- 18095511
TI  - Valvular chondromodulin-1 expression is downregulated in a rabbit model of
      infective endocarditis.
AB  - BACKGROUND AND AIM OF THE STUDY: Tissue neovascularization is a major event in
      the development and dissemination of inflammatory diseases, such as infective
      endocarditis (IE). Although the molecular triggers which allow vascular ingrowth
      in the aforementioned avascular regions are not well understood, they may
      represent potential prophylactic or therapeutic targets. Thus, an investigation
      was conducted to determine whether the expression of chondromodulin-1 (Chm-1), an
      anti-angiogenic protein, is dysregulated in mitral valves in a rabbit model of
      IE, and whether Chm-1 transcripts are differentially expressed in various heart
      tissues. METHODS: Five groups of animals (seven per group) were studied: group I
      was untreated controls; group II received (intravenously) 6x10(6) colony-forming
      units of Staphylococcus aureus; group III underwent mitral valve surgery; and
      groups IV and V underwent surgery and received S. aureus (as per group II), with
      tissues sampled at 6 and 12 h after surgery, respectively). Mitral valve surgery
      was performed by sewing a Dacron patch onto the valve, thereby creating a lesion
      and causing valve insufficiency. Explanted hearts were dissected and Chm-1
      expression was determined using both conventional and real-time RT-PCR. RESULTS:
      Chm-1 transcripts were found in all cardiac regions, with strong expression in
      the heart valves, aorta, and pulmonary artery, and lowest expression in the
      ventricles. Both RT-PCR methods led to similar results; however, the down
      regulation of Chm-1 expression in groups III, IV and V compared to controls was
      more pronounced in the real-time RT-PCR experiments (89 +/- 28% versus 40 +/-
      28%; 63 +/- 22% versus 29 +/- 19%; and 51 +/- 11% versus 13 +/- 7.4%; Chm-1/GAPDH
      ratio levels relative to the control group in conventional versus real-time RT
      PCRs in groups III, IV and V, respectively). Only the decrease in group V was
      significantly different from group I with both methods (p < 0.05 and p = 0.001).
      Bacteremia alone resulted only in minor changes compared to controls. CONCLUSION:
      It is concluded that valvular Chm-1 expression is down-regulated in the early
      phase of IE, which is likely to promote leaflet vascularization and progression
      of the disease.

PMID- 18095512
TI  - Fungal endocarditis of the eustachian valve in carcinoid heart disease: a case
      report.
AB  - The case is presented of a fungal-origin endocarditis affecting the eustachian
      valve. During surgery for pulmonary and tricuspid valve replacement, a 54-year
      old male with carcinoid disease was found to have a 3-cm vegetation attached to
      the eustachian valve. Histopathological assessment of the vegetation revealed the
      presence of Candida species. The patient made a good postoperative recovery and
      was continued on a three-month course of antifungal therapy.

PMID- 18095513
TI  - The St. Jude Medical cardiac valve prosthesis: long-term follow up of patients
      having double valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Between October 1977 and February 2002, a total
      of 343 patients (mean age 62 +/- 13 years; range: 19-91 years) underwent double
      valve replacement (DVR) with the St. Jude Medical (SJM) heart valve. Among the
      replacements, 337 (98%) were aortic and mitral in nature. Concomitant coronary
      artery bypass was performed in 73 patients (21%). METHODS: Cardiac Surgical
      Associates has maintained an independent database of patients undergoing valve
      replacement with the SJM prosthesis since the valve's first implantation in
      October 1977. Patients were contacted by questionnaire and/or telephone (94%
      complete) between November 2002 and June 2003. The patients' hospital course and
      valve-related events were verified by patient chart review and/or physician
      contact. RESULTS: Operative mortality was 8% (n = 29); mortality was valve
      related in two cases. The mean follow up was 6.5 +/- 6.0 years (range: 1 month to
      24 years); total follow up was 2,226 patient-years. Over 25 years, patient
      freedom from late mortality was 62%, and from valve-related mortality 78%.
      Freedom from thromboembolic events was 82% (93% from permanent defect), from
      bleeding events 76%, from endocarditis 98%, from valve thrombosis 99.9%, and from
      reoperation 98%. Six reoperations were carried out in five patients (2%), valve
      repair or replacement in five (2%), and suture closure of paravalvular leak in
      one patient (0.3%). There were no valve structural failures reported. CONCLUSION:
      The SJM valve has proven to be an effective and durable heart valve prosthesis.
      Over the long-term, the event rate is low and there is excellent freedom from
      reoperation in the double valve configuration.

PMID- 18095514
TI  - Mid-term results after Epic xenograft implantation for aortic, mitral, and double
      valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the mid-term
      results after implantation of the stented porcine xenograft (Epic valve with Linx
      anticalcification treatment) in elderly patients. METHODS: A total of 1,368
      patients undergoing aortic valve replacement (AVR; n = 1,168), mitral valve
      replacement (MVR; n = 101) or double valve replacement (DVR; n = 105) between
      November 2001 and November 2006, was evaluated. The indication for Epic
      implantation was patient age > or = 70 years, with pathology not amenable to
      valve repair. Outcome was assessed by reviewing a prospectively acquired hospital
      database, in addition to annual clinical follow up. RESULTS: The mean patient age
      was 76 +/- 6 years (AVR), 73.7 +/- 6 years (MVR), and 73.1 +/- 7 years (DVR);
      among these patient subgroups, 50.3%, 65.3% and 57.7%, respectively, were female,
      and 16.4%, 25.5% and 40.0% presented with endocarditis. The logistic EuroSCORE
      predicted risk for mortality was 14.1 +/- 14%, 19.3 +/- 18%, and 20.3 +/- 20%,
      respectively. Additional surgical procedures included mitral valve repair in 103
      patients (all AVR), CABG in 587 patients (515 AVR, 29 MVR, 43 DVR), left atrial
      ablation therapy in 70, 16 and nine patients respectively, and surgery on the
      thoracic aorta in 54, zero and 12 patients, respectively. The mean aortic cross
      clamp time was 72 +/- 28, 84 +/- 44 and 133 +/- 48 min after AVR, MVR and DVR,
      respectively. Freedom from stroke events after five years was 99.0 +/- 0.3%, 97.3
      +/- 1.9% and 100%, respectively; freedom from bleeding events after five years
      was 99.5 +/- 0.2%, 100% and 99.0 +/- 1.0%, and actuarial freedom from reoperation
      due to prosthetic valve endocarditis 98.9 +/- 0.7%, 96.7 +/- 1.9% and 92.4 +/-
      3.4%. Among these patients groups, early mortality was 8.0 +/- 0.8%, 17.8 +/-
      3.8% and 21.9 +/- 4.0%, and five-year survival 77.0 +/- 4.1%, 71.7 +/- 4.5% and
      55.5 +/- 6.3%. Perioperative survival in non-endocarditis patients undergoing
      isolated valve surgery was 95.8 +/- 0.9%, 96.4 +/- 3.5% and 90.0 +/- 6.7% after
      AVR, MVR or DVR, respectively, while the five-year survival was 90.6 +/- 1.5%,
      89.3 +/- 5.8% and 90.0 +/- 6.7%. CONCLUSION: Clinical outcome at five years after
      porcine valve replacement using the Epic xenograft was satisfactory in elderly
      patients. The clinical effectiveness of the Linx anticalcification treatment
      remains to be proven during longer-term follow up.

PMID- 18095515
TI  - Freedom from structural valve deterioration among patients aged < or = 60 years
      undergoing Freestyle stentless aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Certain theoretical arguments suggest that a
      stentless bioprosthetic valve may be less subject to calcification and
      degeneration compared to an equivalent stented bioprosthesis. The study aim was
      to define the long-term clinical outcomes, including freedom from structural
      valve deterioration (SVD), among relatively younger patients after aortic valve
      replacement (AVR) with the Freestyle aortic bioprosthesis. METHODS: A total of
      725 patients at eight study sites underwent AVR with the Freestyle stentless
      aortic bioprosthesis. Of these patients, 57 (7.9%) were aged < or = 60 years at
      the time of surgery. All clinical data were recorded prospectively. RESULTS: The
      total follow up for the group was 4,900 patient-years; the mean follow up per
      patient was 6.8 +/- 3.6 years; median 7.2 years; range: 0 to 13.3 years).
      Survival at 12 years was 65.0 +/- 11.6% for patients aged < or = 60 years at
      implant, and 33.1 +/- 5.3% for those aged > or = 61 years. Freedom from cardiac
      death was 94.6 +/- 6.6% and 70.7 +/- 7.5%, respectively. Freedom from SVD at 12
      years was 92.4 +/- 8.0% for patients aged < or = 60 years at implant, and 92.3 +/
      5.0% for those aged > or = 61 years (p = 0.58). There was no significant
      difference in freedom from reoperation at 12 years between the younger and older
      age groups (p = 0.16). CONCLUSION: The Freestyle stentless aortic bioprosthesis
      was associated with excellent clinical outcomes through 12 years of follow up.
      Freedom from cardiac death was excellent. Measures of bioprosthesis durability
      remained outstanding through 12 years, with no difference in freedom from SVD or
      from reoperation between patients aged < or = 60 years and those aged > or = 61
      years at the time of implant. Inasmuch as valve durability may influence
      decisions between a tissue and a mechanical valve in younger patients, these data
      help to support use of the Freestyle valve in patients aged < or = 60 years.

PMID- 18095516
TI  - Single leg separation prevalence among explanted Bjork-Shiley prosthetic heart
      valves.
AB  - BACKGROUND AND AIM OF THE STUDY: Bjork-Shiley convexo-concave (BSCC) prosthetic
      heart valves are believed to have been implanted in over 86,000 patients
      worldwide. Limited data are available on the prevalence of single leg separations
      (SLS) of the valves' outlet struts, a potential precursor to complete valve
      fracture. METHODS: Data maintained by the manufacturer, including results of
      examinations for SLS in explanted valves, were merged with available information
      on the characteristics of the valve. The prevalence of SLS in the examined valves
      was calculated according to valve angle, size, position, and study. RESULTS:
      Among 343 examined valves, the overall prevalence of SLS was 8.2%, but this
      varied significantly by valve size, being three-fold higher among 29+ mm valves
      than among smaller valves, with statistically non-significantly higher
      prevalences among mitral than aortic, and among 70 degrees than 60 degrees
      valves. By applying the size, position and angle-specific SLS prevalences to the
      worldwide valve distribution, it is estimated that SLS may be present in 6.8%
      (95% confidence limits 4.1-9.4%) of all BSCC valves. CONCLUSION: These findings
      suggest that SLS may affect between 820 and 1,880 of the almost 20,000 BSCC
      valves among surviving patients worldwide. Such estimates help frame the context
      for potential patient screenings, should imaging and acoustic techniques to
      detect SLS become available.

PMID- 18095517
TI  - Does valve design impact the maximum implantable bioprosthetic diameter? A
      prospective, multicenter observational study.
AB  - BACKGROUND AND AIM OF THE STUDY: The effective orifice area index (EOAI) of
      bioprosthetic aortic valves portends the long-term left ventricular mass
      regression and longevity of patients with aortic valve disease. The
      manufacturers' stated EOA per valve size may lead to inaccurate comparisons if
      the valve design allows a different-sized prosthesis to be implanted for any
      given true annular diameter. This prospective, observational study was undertaken
      in order to evaluate the relationship between the true annular diameter and the
      different sizers that can be accommodated in any given annulus, along with the
      resultant size and type of bioprosthesis implanted. METHODS: An interim analysis
      was undertaken of 318 aortic valve replacement patients among a study group of
      1,850 patients undergoing surgery at 21 U.S. sites between January 2004 and
      October 2006. Following valve excision and annular debridement, the true annulus
      size was determined using a Medtronic universal sizer (UNIV), followed by the
      largest Medtronic Hancock II/Mosaic (MM) and Edwards Perimount (EP) standard
      aortic sizer which fitted safely, and the findings recorded. Details of the
      actual bioprostheses implanted were recorded, and outcomes with 247 MM or EP
      implants were analyzed (71 patients received other prostheses). RESULTS: The
      largest fitting trial sizer was smaller than the UNIV sizer in 108 patients (34%)
      using the EP sizer compared to 17 patients (5.3%) using the MM sizer (p < 0.001).
      Conversely, the largest fitting trial sizer was at least one size larger than the
      true annular diameter in 123 patients (38.7%) using the MM sizer compared to 17
      patients (5.3%) using the EP sizer (p < 0.001). In total, 115 of 130 (88.5%) MM
      implants compared to 59 of 119 (49.6%) EP implants were equal to or greater than
      the UNIV (p < 0.001). CONCLUSION: For any given true annular diameter, a larger
      MM sizer and implanted prosthesis versus EP can be accommodated, which may
      explain the variation in the advertised EOA.

PMID- 18095518
TI  - Comparing warfarin to aspirin (WoA) after aortic valve replacement with the St.
      Jude Medical Epic heart valve bioprosthesis: results of the WoA Epic pilot trial.
AB  - BACKGROUND AND AIM OF THE STUDY: Patients with bioprosthetic heart valves have a
      higher risk of developing peripheral arterial embolic phenomena than the normal
      population. Antithrombotic therapy during the early postoperative period after
      bioprosthetic aortic valve replacement (BAVR) is controversial. This prospective
      pilot study sought to investigate the feasibility of a larger trial and the
      efficacy of postoperative warfarin compared to acetyl salicylic acid (aspirin;
      ASA) in patients after AVR with the St. Jude Epic porcine bioprosthesis (SJEP),
      and the feasibility of conducting a larger trial. METHODS: Patients undergoing
      isolated BAVR were allocated at random to two groups, each of which received
      different antithrombotic therapies: (i) warfarin (INR; range 2-3) for the first
      three months, followed by ASA (100 mg/day); or (ii) ASA alone (100 mg/day).
      RESULTS: During 2003 and 2004, a total of 75 patients underwent isolated BAVR
      with the SJEP. Six patients who developed postoperative de-novo atrial
      fibrillation that did not revert to sinus rhythm were excluded from the analysis,
      but included in the follow up. One postoperative cerebral ischemic event occurred
      in each group between 24 h and three months (2.8% versus 2.9%, p = NS). The rates
      of major bleeding, stroke-free survival and overall survival were similar in both
      groups. CONCLUSION: The early results of this WoA Epic pilot trial did not
      support the suggestion that patients receiving the SJEP, and tissue valves in
      general, should be administered warfarin to prevent valve thrombosis and
      peripheral arterial embolic phenomena.

PMID- 18095519
TI  - Age-related changes in collagen synthesis and turnover in porcine heart valves.
AB  - BACKGROUND AND AIM OF THE STUDY: Although the six-month-old pig is commonly used
      as a model to study human heart valve biology and various age-specific valve
      diseases, the correlation of porcine valve biology and development with that of
      humans has not been thoroughly assessed. Given the important role of the matrix
      in valve function, the aim of this study was to characterize porcine valve matrix
      structure and collagen turnover during development and aging. METHODS: Porcine
      aortic valves (AV) and mitral valves (MV) were examined throughout fetal
      development and postnatally at six weeks, six months and six years, using Movat
      pentachrome staining and immunohistochemistry for collagen III, markers of
      collagen synthesis (molecular chaperone HSP47, hydroxylating enzyme prolyl-4
      hydroxylase (P4H), cross-linking enzyme lysyl oxidase (LOX)) and collagen
      degradation (matrix metalloproteinase (MMP)-13), and a marker of an 'activated'
      cellular phenotype, smooth muscle alpha-actin (SMalphaA). An analysis of variance
      was used to compare the staining intensities. RESULTS: Cell density measurements
      showed layer differentiation in the first trimester (p < 0.003), and this
      decreased ten-fold from the second trimester to six years of age (p < 0.025).
      Matrix turnover was identified by the co-localization of P4H, HSP47 and MMP13,
      and correlated to an 'activated' cellular phenotype. SMalphaA expression was
      noted on the inflow surface of both valves. P4H and LOX were maximally expressed
      around mature collagen (p < 0.001). P4H increased during fetal development (p <
      0.01) and in the six-year-old AV fibrosa (p < 0.05). Collagen-related markers
      were consistently higher in the AV than MV (HSP47 in fetal; P4H, Col III, and LOX
      in six-year-old). CONCLUSION: The substantial matrix changes shown in this
      porcine study provide further insight into the role of matrix turnover during
      development and aging and should be considered when using the porcine animal
      model to study age-specific human diseases.

PMID- 18095520
TI  - Modulation of the p38MAPK pathway in failing human myocardium secondary to
      rheumatic heart disease.
AB  - BACKGROUND AND AIM OF THE STUDY: It is well established that rheumatic heart
      disease can induce congestive heart failure, a condition in which the heart is
      unable to pump out all of its blood content. It was hypothesized that modulation
      of the p38MAPK signal and cardiomyocyte apoptosis may result in an aggravation of
      heart failure secondary to rheumatic heart disease. METHODS: Ventricular tissues
      were collected from healthy (control) subjects and from patients diagnosed with
      rheumatic heart disease and symptomatic heart failure in NYHA functional classes
      II to IV. Apoptosis was monitored using terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling (TUNEL) staining. The protein expression of
      p38MAPK, p-p38MAPK and, MKP-1 were determined with Western blotting, and P38MAPK
      activation with an immunoprecipitation-kinase assay. RESULTS: Compared to
      controls, TUNEL-positive cells were significantly higher in heart failure
      patients in relation to NYHA class (0.33 +/- 0.53% versus 7.38 +/- 3.51%, 11.85
      +/- 3.72% and 19.86 +/- 4.94% in classes II, II and IV, respectively). In class
      II, p38MAPK activity was markedly activated and MKP-1 depressed. In classes III
      and IV, p38MAPK, p38MAPK activity and p-p38MAPK remained significantly elevated,
      while MKP-1 was decreased. Moreover, p38MAPK and p-p38MAPK activities in classes
      III and IV were higher than in class II. With progression of heart function, MKP
      1 was clearly depressed, while p38MAPK activity was elevated in class IV patients
      compared to those in classes II and III. CONCLUSION: The study results show that
      mechanical overloading of the failing human heart secondary to rheumatic heart
      disease results in a differential regulation of the MAPK activity pathway, and a
      corresponding increase in apoptosis.

PMID- 18095521
TI  - Reoperative quadrivalvular surgery including Ross reversal for complex left
      ventricular outflow tract obstruction.
AB  - The case is presented of a congenital left ventricular outflow tract (LVOT)
      obstruction caused by a malpositioned hypertrophied papillary muscle. The patient
      was initially treated with subaortic membrane resection that did not address the
      papillary muscle. Subsequently, she underwent a Ross procedure after her native
      aortic valve had deteriorated. Neither of these operations alleviated the
      symptoms, nor did they relieve the LVOT obstruction caused by the papillary
      muscle. Shortly after the Ross operation the autograft dilated and caused severe
      regurgitation, whereupon the patient's symptoms worsened. Herein are presented
      the authors' considerations in repairing or replacing each of the patient's four
      valves, including reversing the Ross procedure, in an attempt to repair the
      congenital defect and minimize the need for future surgery.

PMID- 18095522
TI  - Incidental mobile aortic valve lesion: a case of aortic valve fenestration.
AB  - The case is reported of a 72-year-old patient with a mobile aortic valve lesion
      discovered incidentally by echocardiography performed in the setting of coronary
      artery bypass graft (CABG) surgery. Definitive identification of this lesion was
      not possible by transthoracic echocardiography or transesophageal
      echocardiography alone. Pathological examination of the excised aortic valve led
      to a diagnosis of aortic valve fenestration (AVF) bridging strand rupture. AVFs
      are common, usually asymptomatic, and of little clinical significance. However,
      rupture of a bridging strand can produce aortic insufficiency and require
      surgical correction.

PMID- 18095523
TI  - Trans fats, dyslipidemia and the metabolic syndrome: are we missing the cream?

PMID- 18095524
TI  - Developing high-quality health-care workplaces: facilitators and barriers.

PMID- 18095525
TI  - A nurse's role in hospital design and development.

PMID- 18095526
TI  - Nursing leadership is crucial in the fight against HIV/AIDS.

PMID- 18095527
TI  - Nursing students' general knowledge and risk perception of pandemic influenza.
AB  - The threat of an influenza pandemic continues to grow, and various institutions
      have started planning initiatives to manage the potentially high rates of
      mortality, morbidity and absenteeism. The authors surveyed nursing students at
      the University of Alberta to determine their general knowledge of, and perception
      of risk associated with, pandemic influenza. The results indicated that there are
      many misconceptions about the nature of a potential influenza pandemic that
      affect nursing students' perceptions of personal and familial risk. It is
      imperative that nursing students receive adequate information, education and
      preparation along with the necessary personal protection equipment if they are
      going to be relied upon as a labour reserve in the event of a pandemic.

PMID- 18095528
TI  - Integration of nurse practitioners into a family health network.
AB  - A randomized controlled study called Anticipatory and Preventative Team Care
      (APTCare) explored a new role for nurse practitioners (NPs) within a
      multidisciplinary team. The aim of the study was to evaluate whether integrating
      NPs and a pharmacist was an effective approach for the management of patients
      living with multiple chronic illnesses. Over an 18-month period, three part-time
      NPs and a pharmacist became part of a rural Family Health Network (FHN). They
      established relationships with study patients and collaborated to provide optimum
      care. Each NP had 40 patients, all of whom received care in the home. Study
      results showed that an initial home visit was invaluable for establishing a care
      plan, developing a relationship with the patient and assessing the home
      environment. Ongoing monitoring at home, however, was found to be an inefficient
      use of the NP role. By the end of the study, all clinicians agreed that the NP
      role had been successfully integrated into the multidisciplinary team.

PMID- 18095529
TI  - Gail Fones: retired nurse brings experience and hope to Uganda.

PMID- 18095530
TI  - A question of balance.

PMID- 18095531
TI  - Quality work environments: the time is now.

PMID- 18095532
TI  - Is there a future in print?

PMID- 18095533
TI  - The developmental origins of conversion disorders.
AB  - Attachment theory offers a novel developmental framework for understanding
      conversion reactions as having phylogenetic roots in two different innate animal
      defense behaviours: The 'freeze response' and 'appeasement defense behaviours'.
      From this perspective, conversion symptoms reflect two distinct, threat-elicited
      emotional responses, which are primed in context-dependent developmental
      experiences (pathways) and underpinned by different neurobiological mechanisms.
      The first of these two developmental pathways to conversion disorder involves the
      organization of self-protective strategies that incorporate components of the
      freeze response and involve inhibition of negative affective states in the
      context of punishment by caregivers. The second of these pathways involves the
      organization of self-protective strategies that incorporate innate appeasement
      defense behaviours in the context of unpredictable parental behaviours that
      threaten children's physical safety or emotional health. Seen from this
      developmental perspective, children with conversion disorders are not a
      homogenous group but fall into two distinct functional groups requiring different
      types of treatment.

PMID- 18095534
TI  - Parent management training as a treatment for children with oppositional defiant
      disorder referred to a mental health clinic.
AB  - Parent Management Training (PMT) has been shown to be an empirically supported
      intervention in ameliorating antisocial behaviour problems. Less evidence is
      available to demonstrate the effectiveness of PMT in routine public-health
      oriented community-based settings where the presence of comorbid disorders
      complicates the picture. The current study was undertaken to investigate the
      effectiveness of PMT as a treatment for primary school-age children with
      Oppositional Defiant Disorder (ODD) and comorbid disorders offered by clinical
      staff as part of clinical practice. An Australian sample of 94 parents of
      children diagnosed with ODD by structured interview was provided with eight
      sessions of PMT. Measures used to assess changes in child behaviour symptoms were
      the Eyberg Child Behavior Inventory, the Parent Stress Index Child Domain, and
      the Child Behavior Checklist. Clinically relevant and statistically significant
      outcome results were found at posttreatment and at 5 months follow-up. There was
      a reduction in child symptomatology but no evidence of any effect of comorbidity
      on outcome. These findings are important for the clinical field as they show that
      PMT is a robust intervention suitable for routine clinical practice even when
      comorbid disorders are present in addition to ODD.

PMID- 18095535
TI  - Death understanding and fear of death in young children.
AB  - The purpose of this study was to test whether the developmental acquisition of a
      mature concept of death, that is, understanding death as a biological event,
      affects young children's fear of death. Ninety children between the ages of 4 and
      8 participated in an interview study in which their understanding of death and
      their fear of death were both assessed. Levels of general anxiety were also
      measured via parent report. A regression analysis indicated that more mature
      death understanding was associated with lower levels of death fear, when age and
      general anxiety were controlled. These data provide some empirical support for
      the widely held belief that discussing death and dying in biological terms is the
      best way to alleviate fear of death in young children.

PMID- 18095536
TI  - 'All that glitters is not gold': misdiagnosis of psychosis in pervasive
      developmental disorders--a case series.
AB  - The early literature established the validity of the distinction between early
      onset schizophrenia and autism. In the modern context of increasing recognition
      of pervasive developmental disorders (PDD) and a growing interest in very early
      onset schizophrenia and other childhood onset psychoses, this clinical
      distinction is often difficult to make. This article looks at problems arising
      from overdiagnosing psychosis in those with PDD. Four case examples of
      misattributed diagnosis of psychosis are described. The features that were
      mistaken for psychotic phenomena are described and explained and successfully
      treated in the context of a diagnosis of PDD. The article describes problems of
      reliability of ascertaining subjective mental phenomena and the range of mental
      phenomena that need to be recognized in PDD. The overlap of abnormal perceptions
      and cognitions in both these conditions is described with reference to the
      literature. It is evident that more needs to be done to improve diagnostic
      reliability of psychosis in PDD, by improving clinical awareness and research
      tools.

PMID- 18095537
TI  - A qualitative investigation of fathers' experiences of looking after a child with
      a life-limiting illness, in process and in retrospect.
AB  - Child life-limiting illnesses are those from which there is no reasonable hope of
      cure and from which children will die. Only recently have these illnesses been
      recognized as a discrete category and thus relatively little research has focused
      specifically upon this group of children and their families. This study utilized
      qualitative methods to investigate the experience of fathers, a group who are
      often under-represented in child illness research. The research aim was to gain
      an understanding of fathers' experiences of having a child with a life-limiting
      illness, its impact upon them, and their perceptions of service provision. The
      data from eight interviews was analysed using Interpretative Phenomenological
      Analysis. Four main themes emerged highlighting the fathers' feeling that their
      world had been turned upside down, how they lived with the knowledge their child
      would die, how men perceive themselves as different from women, and the fathers'
      wish to contribute to changing and improving how other fathers might cope with a
      child with a life-limiting illness. The results are discussed particularly in
      relation to gender issues. Various implications for clinical practice and service
      provision are considered. Suggestions are also made for future research.

PMID- 18095538
TI  - The different stages and actors involved in the process leading to the use of
      adolescent mental health services.
AB  - Although a substantial number of adolescents suffer from emotional or behavioural
      problems, only a minority receive mental health care. In order to understand this
      discrepancy, this article aims to increase insight into the help-seeking process.
      First, a model of the help-seeking process for adolescent psychopathology was
      formulated. This model takes into account the sequential nature of help seeking
      and the involvement of multiple actors (adolescents, parents and teachers) and
      service providers (general practitioners, mental health care professionals,
      teachers, and friends/relatives). Using structural equation modelling, the model
      was empirically tested on 114 Dutch adolescents (aged 12-17 years), who were
      selected for having emotional or behavioural problems from a representative
      general practice sample. Of these 16.5% had used mental health services. The
      sequence of stages and the actors involved in the process leading to mental
      health care use was similar across gender. Parents and adolescents had a
      comparable impact on this process. The general practitioner functioned as
      gatekeeper to mental health care, whereas the teacher's role in the process was
      limited. Interventions aimed at increasing adolescent mental health service use
      should be directed at parents and adolescents, and at the roles of school
      personnel and general practitioners in the detection of problems and referral.

PMID- 18095539
TI  - Internet suicide in Japan: implications for child and adolescent mental health.
AB  - Internet suicide, also known as 'net suicide', is a phrase which has become one
      of the most notorious terms to the Japanese in recent times. 'Net suicide' refers
      to suicide pacts that are prearranged between strangers who meet over the
      internet. Japan has one of the highest suicide rates in the world with 32,325
      people killing themselves in 2004. A worrying new trend of net suicide has
      emerged; as many as 60 people a year have died of this method and the numbers
      continue to rise. This phenomenon, however, does not limit itself to Japan; for
      instance in February 2005, the death of two strangers in London, believed to be
      Britain's first internet suicide, has given cause for concern that this could set
      a precedent for future such events in Europe and elsewhere. Although there is
      much research regarding suicide pacts, far less is known about such 'net suicide'
      pacts. Suicide is a multifaceted problem encompassing cultural, social, religious
      and economic dimensions, and suicide prevention is therefore best managed within
      a multidisciplinary framework. By examining this Japanese phenomenon, I conclude
      that individuals as well as society will have to play a complex, dynamic and
      interactive role in preventing future tragedies.

PMID- 18095540
TI  - Quality of life from research and clinical perspectives: an example from
      paediatric psycho-oncology.
AB  - In clinical oncology and research, health-related quality of life (HRQL) of
      patients has increasingly gained attention. Although there is agreement that HRQL
      is a multidimensional construct incorporating primarily the patient's evaluation
      of his/her life, the construct lacks a uniform model of conceptualization. This
      article briefly outlines definitions and methods of assessing quality of life in
      children and adolescents. The case report of a 10-year-old boy who underwent
      hematopoietic stem cell transplantation views HRQL from various perspectives.
      Self- and proxy assessments are compared, and the expertise of psychotherapeutic
      work is combined with data gathered by standardized questionnaires.

PMID- 18095541
TI  - Correlates of auditory hallucinations in nonpsychotic children.
AB  - The phenomenon of auditory hallucinations in clinical populations of nonpsychotic
      children is an intriguing and little understood area. To date, investigations in
      this area have reported on a range of correlates, including family histories of
      psychiatric illness, family dysfunction, and significant levels of stress in the
      children themselves. The current study reported on 10 nonpsychotic children drawn
      from a number of community-based child and family agencies that provide
      therapeutic outpatient services. Consistent with previous studies, the present
      study found strong associations with family dysfunction, specifically family
      break-up, as well as significant levels of anxiety and depression in the
      presenting children. In addition, half the children reported the presence of
      imaginary companions. Despite confirmation of some previous findings, many other
      features of this phenomenon remain unanswered, including the different
      psychological functions that hallucinations and imaginary companions may serve
      for emotionally troubled children.

PMID- 18095542
TI  - Can I ever see myself treating a client? Commentary on editorial (11.4) 'Trust,
      collaboration and reflection' by Rudi Dallos.

PMID- 18095543
TI  - [Progress in gut-derived mechanism of multiple organ dysfunction syndrome after
      burns and trauma].
AB  - Multiple organ dysfunction syndrome (MODS) is a serious complication with higher
      mortality in patients with burns and trauma. It is important to study the
      mechanism of MODS for prevention and control of it. Mesenteric lymph mechanism of
      MODS is a new viewpoint of gut-derived mechanism of MODS in recent years. In this
      review, we elucidate the mechanism of gut-derived origin of MODS and role of
      mesenteric lymph path in development of MODS after burns and trauma injury.

PMID- 18095544
TI  - [Protective effects of glycyl-glutamine dipeptide supplement on the heart
      function in burn rats].
AB  - OBJECTIVE: To investigate the protective effects of glycyl-glutamine dipeptide
      supplement on the function of myocardial dynamics in severely burned rats, and to
      explore its mechanism. METHODS: One hundred and thirty-six Wistar rats were
      randomly divided into five groups: i. e, control group (C, n = 8, without burns),
      burn group (B, n = 32), Gln group (Gln, n = 32), Gly group (Gly, n = 32) and Gly
      Gln group (Gly-Gln, n = 32). The rats in the latter four groups were respectively
      treated with tyrosine (1.5 g x kg(-1) x d(-1)), glutamine (1.0 g x kg(-1) x d(
      1)) and tyrosine (0.5 g x kg(-1) x d(-1)), glycine (0.5 g x kg(-1) x d(-1)) and
      tyrosine (1.0 g x kg(-1) x d(-1)), and Glycyl-glutamine dipeptide (1.5 g x kg(-1)
      x d(-1)) after receiving a 30% TBSA full-thickness burn on the back. Glutathione
      (GSH), adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine
      triphosphate (ATP), cell energy charge (EC) and the index of myocardial dynamics
      (ASOP, AODP, LVSP, + dp/dtmax) were measured at 12, 24, 48, 72 post-burn hours
      (PBH). RESULTS: The content of GSH, ATP, EC and the level of aortic systolic
      pressure (ASOP), aortic diastolic blood pressure (AODP), left ventricular end
      diastolic pressure (LVEDP) and maximum rate of intraventricular pressure
      rise/down (+ dp/dtmax) in B, Gln, Gly, Gly-Gln groups were obviously lower than
      those in C group (P < 0.01), while the levels of AMP and ADP showed an opposite
      tendency. Compared with B group, the above indices were ameliorated. The content
      of GSH (72.7 +/- 1.7) micromol/g in Gly-Gln group at 12 PBH was obviously higher
      than that in Gln group (67.8 +/- 3.8) micromol/g (P < 0.01). The levels of EC and
      AOSP were obviously higher in Gly-Gln group than that in Gln group (P < 0.01).
      The level of GSH, EC, AOSP in Gly-Gln groups were obviously higher than those in
      Gly group at 48 PBH. CONCLUSION: Glycyl-glutamine dipeptide, Gly and Gln
      supplementation after burns can improve the content of GSH and high energy
      phosphate compound, and suppress the decline of myocardial dynamics function. The
      effects of Glycyl-glutamine dipeptide is better than single Gly or Gln,
      indicating that the protective effect on myocardial function after severe burns
      by Gln and Gly is synergistic.

PMID- 18095545
TI  - [The protective effect of high density lipoprotein on the lung function of rats
      with severe burns].
AB  - OBJECTIVE: To explore the protective effect of high density lipoprotein on the
      lung function of rats with severe burns. METHODS: One hundred and thirty-five
      Wistar rats were employed in the study and were randomly divided into control (n
      = 15, without injury), burn (n = 60, with 30% TBSA full-thickness burn on the
      back) and experimental [(n = 60, with the injection of HDL (80 mg/kg) via the
      caudal vein immediately after burns)] groups. The rats in the latter two groups
      were resuscitated with intraperitoneal isotonic saline (50 ml/kg) 30 minutes
      after burns. The serum content of ICAM-1 and TNF-alpha as well as the blood
      content of PCO2 and PO2 of the rats in burn and experimental groups were
      determined at 12, 24, 48 and 72 post-burn hours (PBH) and in control group. The
      pathological changes in the lung tissue of the rats in all groups were observed
      under light microscope and electronic microscope at 48 PBH. RESULTS: PCO2 and the
      contents of ICAM-1 and TNF-alpha in burn group were significantly higher, but the
      PO2 was lower than those in control group at each time-point (P < 0.05 or P <
      0.01). There were no obvious differences in the above indices between the
      experimental and control groups (P > 0.05), but the ICAM-1 and TNF-alpha levels
      in experimental group were markedly decreased than those in burn group at each
      time-point (P < 0.05 or P < 0.01). The ICAM-1 and TNF-alpha contents in burn
      group at 48 PBH were (3.42 +/- 0.25) microg/L and (4. 04 +/- 0.28) ng/L,
      respectively, which were markedly higher than those in experimental group [(2.24
      +/- 0.14) microg/L, (3.35 +/- 0.22) ng/L, P < 0.05 or P < 0.01]. Dilation of
      capillaries, congestion and inflammatory infiltration in the pulmonary
      capillaries, and loosening of conjunction between pulmonary capillary vascular
      endothelial cells and endothelial swelling were observed in burn group at 48 PBH.
      Compared with the burn group, the injury was markedly alleviated in the
      experiment group, and the pulmonary capillary endothelial cells showed tighter
      junction. CONCLUSION: HDL exhibits a protective effect on the lung function of
      rats with severe burns via reducing the expression of ICAM-1 and TNF-alpha.

PMID- 18095546
TI  - [The protective effect of recombinant glucagons like peptide-2 on intestinal
      mucosa of burn rats].
AB  - OBJECTIVE: To investigate the protective effect of recombinant glucagons like
      peptide-2 (GLP-2) on intestinal mucosa of rats with severe burns. METHODS: SD
      rats of either sex were randomly divided into 4 groups: normal control (N, n =
      6), burn control group (C, n = 6), recombinant GLP-2 group (Gr, n = 6, with
      subcutaneous injection of 100 nmol x kg(-1) x d(-1) recombinant GLP-2 at 4 post
      burn hours (PBH) and synthesized GLP-2 group (G, n = 6, with subcutaneous
      injection of 100 nmol x kg(-1) x d(-1) synthesized GLP-2 at 4 PBH). Except the
      normal control group, all animals in the other groups received a 30% TBSA third
      degree burns, the rats were sacrificed on 7 postburn days (PBD) and the following
      indexes were determined: pathological examination of intestinal mucosa, mucosa
      permeability of intestinal mucosa, the ratio of mucosa wet weight and bowel mass
      or carcase weight, and the protein content of intestinal mucosa. RESULTS:
      Compared with that in burn group [(0.350 +/- 0.040) mg/ml], the mucosa
      permeability significantly decreased in Gr (0.250 +/- 0.026) mg/ml and G (0.243
      +/- 0.008) mg/ml groups, while the ratio of mucosa wet weight and carcase weight,
      the protein content of intestinal mucosa were significantly increased. In
      addition, the content of intestinal mucosal protein in Gr group [(57.9 +/- 2.8)
      mg/g wet weight] was higher than that in G group [(48.9 +/- 4.1) mg/g wet
      weight]. In contrast to normal controls, the villi of intestinal mucosa in rats
      on 7 PBD were obviously shortened and exfoliated, with deranged disposition and
      thinned basal membrane. No obvious difference of the injury was observed between
      Gr and G groups, and the injury was milder when compared with burn group.
      CONCLUSION: Recombinant GLP-2, as well as synthesized GLP-2, exhibits obvious
      protective effect on intestinal mucosa in alleviating injury to intestinal mucosa
      in burn rats.

PMID- 18095547
TI  - [The influence of early enteral immunonutrition on immunological function of body
      and intestine in severely scalded rats].
AB  - OBJECTIVE: To investigate the influence of early enteral immunonutrition on
      immunological function of body and intestine in severely scalded rats. METHODS:
      Sixty-four healthy adult SD rats were subjected to 30% TBSA full-thickness scald
      and randomly divided into enteral nutrition group (EN, n = 32) and enteral
      immunonutrition group (EIN, n = 32). Another 8 healthy rats were enrolled as
      normal controls. The changes in CD3+, CD4+, CD8+ T lymphocyte subsets, the PCNA
      expression in intestinal mucosa,the amount of plasmocytes in lamina propria of
      small intestine and the content of s-IgA in small intestine were determined on 1,
      4, 7 and 10 post-burn days (PBD). RESULTS: (1) CD3+, CD4+ and the ratio of
      CD4+/CD8+ were remarkably declined, while CD8+ was obviously raised after scald
      in EN group, and there were statistically significant differences at most of time
      points when compared with those in control group (P < 0.05 or P < 0.01). CD3+,
      CD4+ and the ratio of CD4+/CD8+ on 7 and 10 PBD in EIN group were obviously
      higher (increased from 4 PBD on, and it was 1.86 +/- 0.25 on 10 PBD) than those
      in EN group (CD4+/CD8+ was 1.26 +/- 0.10 on 10 PBD), while CD8+ in EIN group was
      evidently lower than that in EN group (P < 0.01). (2) The level of PCNA
      expression in intestinal mucosa, the amount of plasmocytes in lamina propria of
      small intestine and the content of s-IgA in small intestine in EIN group were
      increased significantly compared with EN group on 4, 7, 10 PBD (P < 0.05 or P <
      0.01). CONCLUSION: Early enteral immunonutrition can improve immunological
      function of body and intestine after severe scald, with better results than
      enteral nutrition.

PMID- 18095548
TI  - [The protective effect of early insulin treatment on vascular endothelial cells
      in severely scalded rats].
AB  - OBJECTIVE: To investigate the protective effect of insulin on vascular
      endothelial cells of rats at early post-burn stage,and its mechanism. METHODS:
      Adult male Sprague-Dawley rats were randomly divided into 3 groups: i. e, sham
      scald group (n = 7), scald group (n = 7) and treatment group (n = 7). The rats in
      the latter 2 groups were subjected to 30% TBSA full-thickness burns with 94
      degrees C water, and the sham scald rats were treated with 37 degrees C water.
      Intra-peritoneal injection of 40 ml/kg isotonic saline solution and subcutaneous
      injection of 3 units/kg insulin were given to the rats in treatment group after
      being subjected to 30% TBSA full-thickness burns. Subcutaneous injection of equal
      amount of isotonic saline was given to the sham and burn groups. The changes in
      vascular endothelial cell structure were observed with electron microscopy at 24
      post-scald hours(PSH). Meanwhile, the blood glucose contents, the serum levels of
      nitric oxide (NO) and nitric oxide synthetase (NOS) were determined with oxidase
      method and colorimetric method, respectively. RESULTS: The injury of arterial
      endothelial cells in the treatment group was obviously alleviated compared with
      that in burn group. The blood glucose content in the treatment group (7.1 +/- 0.7
      mmol/L) was significantly lower than that in scald group (8.2 +/- 1.0 mmol/L, P <
      0.05), though it was much higher in both groups than that in sham scald group
      (4.9 +/- 0.8 mmol/L, P < 0.01) at 24 PBH. The serum content of NO, total NOS and
      cNOS in treatment group were obviously higher than those in scald group (P <
      0.01), but there was no obvious difference in iNOS content between the two
      groups(P > 0.05). CONCLUSION: Insulin exhibits protective effect on vascular
      endothelial cells in severely scalded rats at the early post-burn stage, and it
      is attributed to its promotion of cNOS level leading to NO production.

PMID- 18095549
TI  - [Influence of heat shock protein 90 on protein serine threonine kinases
      expression in hypoxic cardiomyocytes].
AB  - OBJECTIVE: To explore the effect of endogenous heat shock protein 90 (HSP90) on
      the AKT signaling pathway of hypoxic cardiomyocytes. METHODS: The hypoxia model
      of neonatal rat cardiomyocyte was established. The cells were randomly divided
      into normal control, hypoxia, Geldanamycin (GA, with hypoxia after Geldanamycin
      treatment) groups. The myocardial cell activity and the expression of endogenous
      HSP90 and AKT were determined with MTT and Western blotting, respectively at 1,
      3, 6, 12, 24 and 48 post-hypoxia hours (PHH). The apoptotic index (AI) of
      cardiomyocytes were determined with TUNEL method at 24 PHH. RESULTS: (1) At 24
      and 48 PHH, the activity of cardiomyocytes in hypoxia group and GA group were
      evidently lower than that in control group (P < 0.05). The activity of
      cardiomyocyte in GA group began to decrease at 12 PHH, and it was obviously lower
      than that in hypoxia group at 48 PHH (P < 0.05). (2) At 24 PHH, the AI in hypoxia
      group (10.7 +/- 1.2)% was obviously higher than that in normal control group
      [(1.9 +/- 0.3)%, P < 0.05], while it was obviously lower than that in GA group
      [(26.3 +/- 5.3)%, P < 0.01]. (3) The expression of endogenous HSP90 and AKT in
      hypoxia and GA groups were markedly increased compared with that of normal
      controls at 12 PHH, and it decreased at 24 PHH in hypoxia and GA groups,
      especially in the latter. CONCLUSION: Endogenous HSP90 plays important roles in
      maintaining the cardiomyocyte activity, and its level might affect the expression
      of AKT.

PMID- 18095550
TI  - [Management of hot press injury complicating with blood vessel injury in the
      upper extremity].
AB  - OBJECTIVE: To explore the therapeutic strategy of hot press injury complicating
      with blood vessel injury in the upper extremity. METHODS: Decompression procedure
      was carried out in 8 patients with hot press injury complicating with blood
      vessel injury in the upper extremities, but the effect was not of satisfactory
      because there were injuries to brachial, radial and ulnar arteries and also
      injury to the superficial or deep palmar arch. The blood vessels were repaired
      with direct anastomosis, anastomosis with flexion of the limb, or transplantation
      with great saphenous vein, and the wounds were covered with intermediate split
      thickness skin graft or pedicled thoraco-abdominal skin flap. RESULTS: One
      patient with repair of the brachial artery and intermediate split thickness skin
      graft received amputation 4 weeks after operation because of lack of soft tissue
      coverage. The blood supply recovered completely in the other patients, so the
      affected limbs were saved. CONCLUSION: Prompt exploration and repair of blood
      vessel, and coverage of the wound with healthy soft tissue are key procedures for
      the management of hot press injury complicating with blood vessel injury in the
      upper extremities.

PMID- 18095551
TI  - [Study on the relationship between the human leucocyte antigen-DR expression on
      CD14+ monocytes and sepsis].
AB  - OBJECTIVE: To investigate the changes in the expression of HLA-DR on CD14+
      monocytes of burn patients with delayed resuscitation, and to analyze the
      relationship between it and sepsis. METHODS: Twenty-five patients with total burn
      surface area over 30% TBSA and delayed resuscitation were enrolled in the study,
      among which 7 were complicated by sepsis during hospitalization. Peripheral blood
      was collected on 1, 3, 7, 14 and 28 post-burn days (PBD), and the blood of the
      patients with sepsis were also collected on the 1 and 2 days after the occurrence
      of sepsis. Twenty healthy volunteers were enrolled as controls. Expression rate
      of HLA-DR on CD14+ monocytes was determined by flow cytometry. The level of TNF
      alpha and IL-10 were measured by ELISA. RESULTS: Expression rate of HLA-DR
      antigen on CD14+ monocytes in burn patients without sepsis on 1, 3, 7, 14, 28 PBD
      were (15 +/- 6)%, (7 +/- 5)%, (26 +/- 17)%, (28 +/- 16)% and (47 +/- 16)%,
      respectively, which were obviously lower than that of healthy people [(92 +/-
      10)%, P < 0.01], and it was also markedly lower on 1 and 2 days after the
      occurrence of sepsis than that of controls and those of patients without sepsis
      on 1, 7, 14, 28 PBD (P < 0.01). The positive rate and concentration of TNF-alpha
      in patients with sepsis were obviously higher than that of healthy people and
      patients without sepsis (P < 0.05 or P < 0.01). There was a negative correlation
      between the expression rate of HLA-DR on CD14+ monocytes and IL-10 levels, and it
      showed significant difference on 1, 7, and 28 PBD (r = -0.9963, -0.7459, -0.8474,
      respectively, P < 0.01). CONCLUSION: Immune function is suppressed and
      proinflammatory mediators are excessively released in severely burn patients
      after delayed resuscitation, especially when complicated with sepsis. Expression
      of HLA-DR on CD14+ monocytes may be an useful parameter for monitoring the immune
      function of burn patients.

PMID- 18095552
TI  - [Expression of myeloid cell triggering receptor-1 in monocytes at early post-burn
      stage].
AB  - OBJECTIVE: To investigate the expression of triggering receptor expressed on
      myeloid cells (TREM-1) in monocytes of burn patients at early post-burn stage,
      and its significance. METHODS: The monocytes of 8 healthy volunteers (A group),
      29 patients with mild and moderate burn (B group), and 9 patients with severe and
      very serious burns (C group) were isolated from the blood, and the THEM-1 mRNA
      and protein expression were determined by semi-quantitative RT-PCR and flow
      cytometry, respectively. The plasma levels of TNF-alpha, IL-1beta were determined
      by ELISA method. RESULTS: The value of TREM-1 mRNA expression in A, B and C
      groups were 0.74 +/- 0.13, 1.24 +/- 0.09, and 1.46 +/-0.07, respectively, and the
      expression rates on cell surface in the 3 groups were (9 +/- 4)%, (51 +/- 6)%,
      and (71 +/- 7)%, respectively, and there were significant differences among the
      three groups (P = 0.000). the plasma levels of TNF-alpha and IL-1beta in B and C
      groups were obviously higher than that in A group (P = 0.000), and they were
      positively correlated to TREM-1 expression (rs = 0.68, 0.72, P = 0.000).
      CONCLUSION: Increased expression of TREM-1 in monocytes of burn patients at early
      post-burn stage is correlated with the release of inflammatory factors,
      indicating that TREM-1 might contribute to the onset and development of acute
      inflammatory response after burns.

PMID- 18095553
TI  - [Inhibitory effect of lanthanum chloride on the expression of inducible nitric
      oxide synthase in RAW264.7 macrophages induced by lipopolysaccharide].
AB  - OBJECTIVE: To explore the influence of lanthanum chloride (LaCl3) on inducible
      nitric oxide synthase (iNOS) expression in RAW264.7 macrophages with
      lipopolysaccharide (LPS) induction, and to investigate its possible mechanisms.
      METHODS: The RAW264.7 macrophages were randomly divided into four groups: i. e,
      control group (without treatment), LaCl3 group (with treatment of 2.5 micromol/L
      of LaCl3 for 24 hrs), LaCl3 + LPS group (with treatment of 2.5 micromol/L LaCl3
      for 24h), and LPS group (with treatment of 1 mg/L LPS for 24 hrs). The iNOS
      protein expression was measured by immunofluorescence and Western blot. iNOS gene
      expression was assayed by reverse transcription-polymerase chain reaction (RT
      PCR). NO production in culture supernatant was assayed by nitrate reductase
      method. RESULTS: Immunofluorescence analysis showed that iNOS was located mainly
      in the cytoplasm. RAW264.7 cells with overexpression of iNOS accounted for 44.4%,
      which was obviously higher than that in LaCl3 + LPS group (11.8%, P < 0.05).
      There was a faint signal of FITC-labeled green tint in control group or LaCl3
      group. The iNOS mRNA and protein expression, and the NO content in LPS group were
      significantly higher than those in control, LaCl3, and LaCl3 + LPS groups (P <
      0.05). CONCLUSION: LaCl3 can suppress LPS-induced iNOS overexpression at mRNA and
      protein level and reduce NO production, indicating that LaCl3 can antagonize the
      excessive activation of iNOS induced by LPS.

PMID- 18095555
TI  - [Effect of the microtubule depolymerization on mitochondria damage in rat
      myocardiocytes early after hypoxia].
AB  - OBJECTIVE: To investigate the effect of microtubule depolymerization on
      mitochondria damage in rat myocardiocytes early after hypoxia. METHODS:
      Myocardiocytes from Wistar rats were isolated according to routine procedure, and
      they were randomly divided into control group, depolymerization group (with
      treatment of 4 micromol/L colchicines in the culture medium), hypoxia group,
      hypoxia and depolymerization group (with treatment of 4 micromol/L colchicines in
      the culture medium combined with low oxygen tension). The changes in distribution
      of the mitochondria were examined with laser confocal microscopy, the morphology
      and the structure of mitochondria was observed by transmission electron
      microscope, the respiration control ratio (RCR) was determined by respirometer,
      and the content of adenosine triphosphate (ATP) in endochylema was detected with
      liquid chromatograph at 20, 30, 60 post-hypoxia minutes (PHM). RESULTS: In
      control group, the mitochondria was in granular form, with regular arrangement,
      while mild changes were observed in depolymerization group. At 20, 30, and 60
      PHM, the disarrangement in distribution and morphologic damage were aggravated in
      hypoxia depolymerization group, and the RCR (1.58 +/- 0.37, 1.51 +/- 0.32, 1.12
      +/- 0.11, respectively) were evidently lower than those in hypoxia group (3.85 +/
      0.56, 2.98 +/- 0.44, 1.79 +/- 0.73, respectively, P < 0.01). The content of ATP
      showed the same tendency at the same time-points (419 +/- 83, 326 +/- 73, 295 +/-
      58 ng/mg) compared with hypoxia depolymerization group [(475 +/- 68, 397 +/- 59,
      336 +/- 67 ng/mg) in hypoxia group]. CONCLUSION: The disarrangement in
      distribution of mitochondria, as well as the damage in mitochondrial structure,
      respiratory, function and energy metabolism, can be aggravated by microtubule
      depolymerization after hypoxia, which indicates that microtubule depolymerization
      plays an important role in the mitochondria damage.

PMID- 18095554
TI  - [Inhibitory effect of epidermal growth factor on apoptosis in HaCaT keratinocytes
      induced by TNF-alpha].
AB  - OBJECTIVE: To explore the effect of epidermal growth factor (EGF) on apoptosis
      induced by TNF-alpha and the expression of PPARbeta in HaCaT keratinocytes.
      METHODS: HaCaT keratinocytes were cultured and randomly divided into A (normal
      control), B (with treatment of 10 ng/ml TNF-alpha for 24 hours), C (with
      treatment of 20 ng/ml TNF-alpha for 24 hours), D (with treatment of 10 ng/ml TNF
      alpha after 20 ng/ml EGF treatment for 4 hours), E (with treatment of 20 ng/ml
      TNF-alpha after 20 ng/ml EGF treatment for 4 hours) groups. The apoptosis of
      HaCaT keratinocytes was observed by flow cytometry. The proliferative activity of
      HaCaT keratinocytes was evaluated by MTT method. The activity of caspase-3 was
      analyzed with caspase colorimetric assay Kit. The changes in the mRNA and protein
      expression of PPARbeta in HaCaT keratinocytes were observed by RT-PCR and western
      blotting after treatment with different concentrations (5, 10, 20, 40 ng/ml) of
      EGF for 4 or 24 hrs. RESULTS: Compared with A and B groups [(32 +/- 6)%, (57 +/-
      6)%], the apoptosis of HaCaT keratinocytes in D and E groups were significantly
      increased [(20 +/- 3)%, (28 +/- 4)%, respectively, P < 0.01], while the survival
      rate of HaCaT keratinocytes in D and E groups increased, and the caspase-3
      activity were decreased (P < 0.01). The expression of PPARbeta mRNA and protein
      in HaCaT keratinocytes reached the peak with the treatment of 20 ng/ml EGF.
      CONCLUSION: EGF can inhibit the apoptosis of HaCaT keratinocytes induced by TNF
      alpha, and it can also increase the expression of PPARbeta.

PMID- 18095556
TI  - [The influence of vacuum-assisted drainage on the growth of capillaries in the
      wound produced by explosion in pig].
AB  - OBJECTIVE: To investigate the influence of vacuum-assisted closure (VAC)
      technique on the growth of capillaries in the wound of the pig produced by
      explosion. METHODS: Four small white pigs were inflicted with 16 explosion wounds
      [(7.3 +/- 1.0) cm2 in area] on both sides of the buttocks, shoulders and hips by
      detonation of a specific type of explosive, and the wounds were randomly divided
      into 2 groups, i. e, control (C, with conventional treatment from 2 post-injury
      day (PID) on and treatment (T, with VAC treatment after debridement from 2 PID
      on) groups, with 8 wounds in each group. Wound tissues of 2mm x 2mm x 2mm in size
      were harvested for pathological examination before treatment and on 1 and 3 post
      treatment day (PTU). The differentiation of adventitial cells were examined with
      light microscope, and the pixel value of desmin positive particles and the
      luminal area of newly formed capillaries were assessed with Image C software.
      RESULTS: Most of vessels in the wound of both groups were in elliptic shape when
      observed in longitudinal section. In C group, few newly formed capillaries
      vessels with lack of pericytes were observed before treatment and on 1, 3 PTD,
      then the number began to increase on 6 PTD. In T group, the number of newly
      formed capillaries with pericytes was increased on 1 PTD, and it continued to
      increase thereafter. The pixel values of desmin positive particles in C group on
      1, 3, and 6 PTD were (91 +/- 54), (199 +/- 85), and (1552 +/- 298), respectively,
      which were obviously higher than those in T group [(2569 +/- 330), (3984 +/-
      377), (9611 +/- 960), P < 0.01]. The area of vessel lumen in C group was (59 +/-
      36), (250 +/- 70), and (938 +/- 287) microm2, respectively on 1, 3, and 6 PTD,
      which was also smaller than those in T group [(818 +/- 234), (4518 +/- 1080), and
      (9058 +/- 1656) microm2, P < 0.01]. CONCLUSION: Compared with conventional
      therapy, VAC can not only accelerate the formation of new capillaries, but also
      enhance the differentiation of pericytes and the process of enwrapping them
      around the vessels, and increase the luminal area of newly formed capillaries.

PMID- 18095557
TI  - [Association between genetic polymorphisms of DNA repair genes XRCC1, XPD, XRCC3
      and the capacity of DNA repair induce by benzene].
AB  - OBJECTIVE: To explore the correlation between genetic polymorphisms of XRCC1,
      XPD, XRCC3 and DNA repair capacity induced by benzene. METHODS: Eighty patients
      suffered from chronic benzene poisoning were investigated. PCR-RFLP was applied
      to detect the single nucleotide polymorphisms on C26304T, G27466A, G28152A,
      G36189A of XRCC1, C22541A, C23591T, A35931C of XPD, C18067T of XRCC3. Cytokinesis
      block micronucleus (CBMN) and alkaline comet were applied to detect the DNA
      repair capacity. RESULTS: The DNA repair capacity of the subjects carrying XPD
      35931C variant allele or carrying XRCC3 18067 C/T variant genotype were higher
      than those carrying corresponding mild genotype. CONCLUSION: There could be a
      correlation between polymorphisms of XRCC3 and DNA repair capacity of DNA damage
      induced by benzene.

PMID- 18095558
TI  - [Investigation of toxigenic microcystis and microcystin pollution in Huayuankou
      Conservation Pool of Yellow River].
AB  - OBJECTIVE: To investigate the contaminative, condition of planktonic algae,
      cyanobacteria, toxigenic microcystis and microcystin in Huayuankou Conservation
      Pool of Yellow River. METHODS: From March 2005 to January 2006, water samples
      were taken 15 times by 2. 5L plastic sampler from Huayuankou Conservation Pool.
      The density of algae were counted by using blood cell counter. Phycocyanin
      intergenic spacer region (PC-IGS) and microcystin synthetase gene B (mcyB) of
      toxigenic microcystis was identified by the whole cell PCR. The concentration of
      microcystin was determined by ELISA kit. The positive results of PCR and ELISA
      were compared. RESULTS: Bacillariophyta, chlorophyta, cyanophyta (cyanobacteria)
      and euglenophyta were main algaes in Huayuankou conservation pool, and the
      dominant algae and cell density changed seasonally. Algae cell density and
      cyanobacteria cell density were higher in summer and autumn than in spring and
      winter. From July to November, 2005, PC-IGS and mcyB were detected positively by
      whole cell PCR. Microcystin was positively detected from July, the concentration
      of microcystin changed from 0 to 0.25microg/L, it was more higher in summer than
      other seasons. CONCLUSION: Toxigenic microcystis and microcystin could be
      detected in Huayuankou Conservation Pool of Yellow River. Whole cell PCR could be
      used to identify toxigenic microcystis.

PMID- 18095559
TI  - [Differences of signaling pathway of lung injury between C57BL/6 and C3H/He mice
      exposed to fine particle].
AB  - OBJECTIVE: To study the differences of signaling pathway of lung injury between
      C57BL/6 and C3H/He mice exposed to fine particle. METHODS: By intratracheally
      instillation, two strains of mice (C57BL/6 mice and C3 H/He) were exposed to fine
      particle once time per day, for continuously two days. Twenty-four hours after
      last time exposure, the mice were killed and the lungs were taken out
      immediately, and put into the liquid nitrogen. By using Affymetrix430 2.0
      genechip, differences of the signaling pathways between C57BL/6 and C3H/He mice
      were found. RESULTS: It was indicated that the ratios of (C57BL/6)/(C3H/He) of
      Igh-6, Mmp2, Timp1, Col1a1, Col1a2, C4 and Hc expression in unexposed mice,and in
      exposed mice were 0.00, -2.40, 0.00, -4.42, -4.92, 6.65 and -1.93, and -2.83,
      2.15, -2.18, 2.40, 2.86, 4.23 and 2.18, respectively. And by further analysis,
      three different signaling pathways were discovered between C57BL/6 and C3H/He
      mice, including inflammatory response pathway, matrix metalloproteinases pathway
      and classical complement activation. CONCLUSION: The results showed that three
      signaling pathways were associated with inflammation. It was suggest that the
      lung inflammation in C57BL/6 mice could be more severe than that in C3H/He mice.
      The possible causation may be the different genetic background between C57BL/6
      and C3H/He mice.

PMID- 18095560
TI  - [Status and characteristic of dietary intake of 12 minority nationalities in
      China].
AB  - OBJECTIVE: To describe the status and characteristic of dietary intake in 12
      minority nationalities. METHODS: 6688 subjects were randomly sampled from 12
      minority nationalities (Mongolian, Hui, Tibetan, Uygur, Miao, Yi, Zhuang, Buyi,
      Man, Yao, Tujia and Kazak). The 24-hour dietary recall method for 3 consecutive
      days was used to collect food intake information, except for the condiment
      intake, which was collected by weighting method. RESULTS: The pattern of staple
      food of minority nationalities were influenced by environment, economic, religion
      and culture food. The consumptions were significantly difference among the 12
      minority nationalities, Yi, Yao and Tujia nationality people consumed more bean
      and bean products, but the consumption of Tibetan, Uygur and Kazak were very low.
      The meat consumption of Tibetan, Zhuang and Yao were high, but the paultry and
      fishery products consumption were very low. Uygur and Kazak nationality had high
      dairy intake level, average daily consumption were over 200g. The minority
      nationality residents who lived in high areas or the north China consumed less
      vegetable comparing with other areas. The daily salt consumption of Uygur and
      Kazak nationality were quite high (over 20g). CONCLUSION: The difference extents
      of the problem on dietary pattern exist among the 12 minority nationalities.
      Nutrition education activities should be implemented to guide the people
      developing and utilizing the local food resource scientifically, to advocate the
      principle of a balanced diet.

PMID- 18095561
TI  - [Epidemiological study on diabetes mellitus in people aged 60 and over].
AB  - OBJECTIVE: To study the epidemiological characteristics of diabetes mellitus in
      Chinese people aged 60 and over based on the data of China Nutrition and Health
      Survey in 2002. METHODS: Fasting plasma glucose (FPG) of 9925 subjects, aged 60
      and over were determined by glucose oxidase method and the prevalence of diabetes
      mellitus was analyzed by gender and by regions. RESULTS: The average FPG of all
      subjects was 5.18 mmol/L adjusted by population distribution based on 2000
      census. Over 29.5% of subjects in metropolis and 21.6% middle cities were
      determined as fasting hyperglycemia (FPG > or = 5.6 mmnol/L). The prevalence of
      DM in old subjects was 6.83%. The prevalence of DM in old subjects of metropolis,
      middle city, 1st, 2nd, 3rd, 4th country was 16.97%, 11.43%, 4.94%, 4.70% and
      1.94% respectively. CONCLUSION: Over 21% of Chinese urban residences aged 60 and
      over suffer from fasting hyperglycemia and the prevalence of DM reached 13.17%.

PMID- 18095562
TI  - [Laboratory analysis and its variety of fat in prepackaged foods].
AB  - OBJECTIVE: To observe the variety of fat analysis of prepackaged foods from
      different labs of China. METHODS: Thirteen foods from seven kinds were selected
      as food samples: cereal products, bean products, meat products, dairy products,
      beverages, nuts, snacks, according to national prepackaged foods consumption
      survey results in 2000. The sample fat contents were analyzed parallelly for
      three times by national standard methods in seven labs from all the country.
      RESULTS: The 93.4% of results were up to grade by Grubbs, Cochran and Dixon
      screening methods. The accuracy of fat analysis was expressed by variety
      coefficiency (C. V%). The C. V% of inner labs and inter labs were from 1.89% to
      5.39% and from 2.64% to 24.14%, the total and average C. V% level were from 3.32%
      to 24.60% and 11.51%. Besides the fish tin and fat-free milk powder (with very
      low fat content), the relative expanded uncertainties of fat detection were from
      6.48% to 34.80% (average 17.62%). CONCLUSION: Fat analysis level in labs from all
      the country was fit for national standards. If fat labeling were focused on its
      middle and high content prepackaged foods, the uncertainty of analysis should be
      controlled in 20%.

PMID- 18095563
TI  - [Bioefficacy of plant carotenoid to vitamin A in school age children].
AB  - OBJECTIVE: To determine the bioefficacy of pure beta-carotene and beta-carotene
      from spinach to vitamin A in schoolchildren of different vitamin A status.
      METHODS: Thirty two schoolchildren aged 7-9 years old were selected and then
      divided into two groups randomly. Each group included 16 subjects, of which the
      vitamin A level of 8 subjects was normal, the other 8 subjects suffered from
      vitamin A deficiency. In the first 7 days, one group was given 5 gram spinach
      (containing 230 microg 2H10-beta-carotene) before lunch and dinner and the other
      group was given pure beta-carotene capsule (containing 200 microg beta-carotene).
      Before breakfast, both groups were given 100 microg 13C10 retinal acetate
      capsule. Blood was drawn on the 3, 7, 8, 22 and 28 day. HPLC and GC-MS were used
      to determine the retinol concentration and enrichment of isotope and then
      calculate the bioefficacy of pure beta-carotene and beta-carotene from spinach to
      vitamin A. RESULTS: The conversion factors of pure beta-carotene to vitamin A in
      oil capsule were: 2.9:1 for the children with normal vitamin A status, 3.2:1 for
      those suffering from marginal vitamin A deficiency. The conversion factors of
      spinach beta-carotene to vitamin A were 10.1:1 and 10.3:1 for the children with
      normal and low vitamin A status, respectively. CONCLUSION: The vitamin A
      conversion bioefficacy of pure beta-carotene from oil capsule is much higher than
      that of spinach. There is no difference of beta-carotene bioefficacy to vitamin A
      for children with different vitamin A status.

PMID- 18095564
TI  - [Intervention of selenium on injured type 1 deiodinase by excessive iodine in
      mice].
AB  - OBJECTIVE: To study the mechanism of the damage resulted from iodine excess and
      to seek suitable selenium intervention dosage. METHOD: 160 BALB/c mice were
      divided into eight groups, the normal control group, the excessive iodine group
      (drunk the water containing potassium iodate 3000 microg/L) and six selenium
      groups (drunk the water containing potassium iodate 3000 microg/L and selenium
      0.1, 0.2, 0.3, 0.4, 0.5 and 0.75 mg/L). The type 1 deiodinase (D1) activities and
      the levels of mRNA in liver, kidney and thyroid were determined by RT-PCR.
      RESULTS: The mRNA levels of D1 restored to normal levels in all of the IS groups,
      while only 0.1-0.4 mg/L selenium supplement groups had normal activities of D1 in
      liver, kidney and thyroid. CONCLUSION: Decline of D1 activities in liver, kidney
      and thyroid seems to be one of the reasons of the damage and should be chosen for
      effective intervention.

PMID- 18095565
TI  - [Effect of green tea polyphenols on behavioral performances in psychological
      stress rats].
AB  - OBJECTIVE: This study was conducted to explore the effects of green tea
      polyphenols modulation on changes of behavioral performances in psychological
      stress rats. METHODS: The animal model of psychological stress was developed by
      restraint stress for 3 weeks. Wistar rats were randomly assigned to five groups
      as follows: control group (CT), stress control group (SCT), and three stress
      groups with low, medium and high-doses of green tea polyphenols modulation
      respectively (SLG, SMG and SHG). The changes of behavioral performances were
      examined by open-field test, water maze and step-through test. Serum levels of
      cortisol, catecholamines, interleukin-6 and interleukin-2 were also detected.
      RESULTS: The levels of serum cortisol were all increased obviously in the four
      stress groups. Furthermore, serum cortisol levels in SMG and SHG were decreased
      than that of SCT. The behavioral performances of SCT rats in open-field test,
      step-through test and water maze were all changed evidently in contrast to that
      of CT rats. On the one hand, the changes of behavioral performances in SLG rats
      were similar to SCT rats. On the other hand, these changes were improved in SMG
      and SHG rats. In addition, compared with CT group, the levels of plasma IL-6 and
      IL-1 were increased clearly in the four stress groups, and the contents of serum
      norepinephrine and dopamine in SCT and SLG groups were decreased dramatically.
      The serum norepinephrine and dopamine levels in SMG and SHG rats were increased
      in contrast to that of SCT rats. CONCLUSION: Our results suggested that
      psychological stress can impair body' s behavioral performances, and moderate
      green tea polyphenols modulation may improve these abnormal changes.

PMID- 18095566
TI  - [Primary investigation on metabolism of hpt gene in transgenic rice modified with
      cowpea trypsin inhibitor gene in rats].
AB  - OBJECTIVE: The metabolism characteristic in the gastrointestinal tract and
      possibility of transfer from gastrointestinal tract into liver and kidney was
      investigated. METHODS: 48 SD rats were allotted into 8 subgroups randomly, 6
      groups rats of them were fed with transgenic rice diets and 2 groups rats were
      fed with non-transgenic rice diets. All rats were fed with transgenic and non
      transgenic rice for two weeks. All rats were fast and sacrificed, the contents of
      stomach, jejunum, the lower part of ileum, cecum and rectum were taken out at 2,
      4, 6, 8, 10 and 24 hours respectively after eating final diets. Fed two groups of
      SD rats with transgenic diet and non-transgenic rice diet respectively for 4
      weeks, the liver and kidney were sampled and stored. All samples was examined by
      PCR. RESULTS: The fragment of hpt was found the was only detected in stomach and
      jejunum, but none of the five fragments was detected in the lower part of ileum,
      cecum and rectum. The degradation of hpt was time-relationship and long-length
      fragment relationship, the longer was the action time, the more serious was the
      degradation. Foreign hpt gene was not detected in liver and kidney. CONCLUSION:
      hpt gene was easy to degraded in gastrointestinal tract and was not detectable in
      hepatic tissue and nephridial tissues.

PMID- 18095567
TI  - [Effects of lactational exposure to soy isoflavones on steroid receptor
      expression in neonate rat ovaries].
AB  - OBJECTIVE: To study the effects of lactational exposure to soy isoflavones (SIF)
      on ovary development in neonate rats. METHODS: Virgin Sprague-Dawley female and
      male rats were fed with soy and alfalfa free diets (SAFD). The pregnant rats were
      randomly divided into six groups with seven animals in each group. Dams in
      different treatment groups received 0, 10, 50, 100, 150 and 200mg/kg bw of SIF
      from postnatal day 5 to 10 (PND5-10) by gavage, respectively. On PND11, female
      litters were killed and ovaries were removed for pathological evaluation and
      detection of estrogen receptor (ER), andron receptor (AR), progesterone receptor
      (PR), proliferating cell nuclear antigen (PCNA) protein expression by
      immunohistochemistry as well as ER, AR, PR mRNA expression by RT-PCR. RESULTS:
      The ratios of ovary weight to body weight increased significantly in 100, 150 and
      200 mg/kg bw groups than that in control group. And the ovary follicles developed
      more quickly in offsprings exposed to SIF. In 150 and 200 mg/kg bw groups, ER,
      PCNA protein and ER mRNA expression in ovaries increased significantly, while PR
      mRNA expression decreased significantly. Other receptor expressions had no
      significant difference from the control group. CONCLUSION: Lactational exposure
      to soy isoflavones could induce adverse effects on ovary development in neonate
      rats, which mechanisms may, at least, partically involved with modification of
      mRNA transcription for ER and PR.

PMID- 18095568
TI  - [Effect of ethanol on the development of mouse neuroblasts].
AB  - OBJECTIVE: To investigate the effect of ethanol on the development of embryonic
      neuroblasts and the relation to ethanol's teratogenicity. METHODS: 12 day mouse
      embryos with 34-36 somites were separated from the dam. The embryonic midbrain
      was cut off and neuroblasts were prepared for primary culture. The neuroblasts
      were cultured with different concentrations of ethanol. After 3-5 days, the cell
      differentiation, neurofilament protein level and apoptosis were detected.
      RESULTS: Differentiation of the midbrain neuroblasts were inhibited by ethanol
      exposure. As the ethanol concentration increasing, the level of neurofilament
      protein decreased and the number of cells undergoing apoptosis increased, showing
      a dose dependant style. CONCLUSION: Alcohol could inhibit the differentiation of
      midbrain neuroblasts, suppressed the express of neurofilament protein and induce
      excessive apoptosis, which may be related to the teratogenic action of ethanol on
      central nervous system.

PMID- 18095569
TI  - [Translocation of p38 MAPK induced by retinoic acid in H9c2 cells].
AB  - OBJECTIVE: To study the distribution of p38 MAPK and translocation of p38 induced
      by all-trans retinoic acid (atRA) in cardiomyocytes. METHODS: H9c2 cells were
      cultured in the normal growth medium containing 10% fetal bovine serum. Cells
      were serum-starved overnight followed by atRA (0.05 micromol/L) treatment or
      SB202190 (10 micromol/L) pretreatment. The localization of p38 under different
      conditions was detected by Confocal Laser Scanning Microscopy. Then the ratio of
      p38 localized in nuclei to cytoplasm was analyzed by a Leica Microsystem. Thus,
      the statistical analysis of these data showed the effects of atRA or SB202 190 on
      p38 translocation. RESULTS: p38 was located more in the cytoplasm without
      stimulation, while in the cells with atRA treatment for 5 min and 30 min, p38
      labeled with green fluorescence in the cytoplasm decreased. The p38 ratio of
      nuclei to cytoplasm showed that there was a significant difference between atRA
      groups and control. As the specific inhibitor of p38, SB202190 could obviously
      inhibited the nuclear translocation of p38 induced by atRA (P < 0.01). And
      compared with control, SB202190 could make the nuclear translocation of p38
      decrease by 26.1%. CONCLUSION: atRA could induce the nuclear translocation of p38
      in cardiomyocytes. And p38 pathway might participate in the regulation of heart
      development.

PMID- 18095570
TI  - [Effect of lycopene on proliferation and cell cycle of hormone refractory
      prostate cancer PC-3 cell line].
AB  - OBJECTIVE: To investigate the effects of lycopene on proliferation of human
      prostate cancer cell line PC-3 and explore its effecting mechanism. METHODS: The
      proliferation of PC-3 cells were analyzed by MTT and H3-TdR incorporation. The
      effects of cell cycle and apoptosis of synchronized cells were observed through
      flow cytometry. RT-PCR methods were used to explore the mRNA expression level of
      cyclin D1, bcl-2, bax. RESULTS: The growth and DNA synthesis of PC-3 cell were
      inhibited with the lycopene concentration increased, and lycopene also could
      change the cell cycle distribution, i. e. increasing the proportion of G0/G1
      phase and descending the proportion of S and G2/M phase, and induce the
      apoptosis. RT-PCR analysis showed that the mRNA expression level of cyclin D1 and
      bcl-2 were down regulated, while the level of bax was up regulated. CONCLUSION:
      Lycopene can induce apoptosis of PC-3, change the cell cycle distribution and
      downregulate the expression of cyclin D1 and bcl-2 and upregulate the expression
      of bax and then restrain cell proliferation.

PMID- 18095571
TI  - [Effects of folate on proliferation and differentiation of neural stem cells in
      vitro].
AB  - OBJECTIVE: To explore the protective effect of folic acid on proliferation and
      differentiation of neural stem cells in vitro. METHODS: On the 14th day of
      gestation, NSCs were obtained. MTT method was used to detect the proliferation of
      NSCs cultured with folic acid of different concentrations and time. After 6 days,
      the NSCs purified were placed into culture dishes of fetus bovine serum. On the
      seventh day of differentiation, double-tabeling immunofluorescence with antibody
      Nestin and BrdU was taken to calculate the number of NSCs by 8 fields of vision
      chosen randomly . RESULTS: Comparing to control group, NSCs of folate group was
      increase and better, and significantly (P < 0.05). CONCLUSION: Folic acid may
      suppress proliferation and differentiation of NSCs efficiently.

PMID- 18095572
TI  - [Study of regulation of Puerarin on blood P-selectin and the expression of aorta
      VCAM mRNA in diabetes].
AB  - OBJECTIVE: To observe the regulation of Puerarin on blood P-selectin and
      expression of aorta vascular cell adhesion molecule (VCAM) in diabetic rats
      induced by Streptozotocin. METHODS: Diabetic rats were induced by intraperitoneal
      injection of STZ. Rats were divided into normal control group, model group, and
      three Puerarin groups (20, 40 and 80 mg/kg, ip) for 16 weeks. After the
      treatment, its cholesterol, low density lipoprotein, high density lipoprotein, P
      selectin, oxidative low density lipoprotein and glycosylated low density
      lipoprotein. Alteration of tissue morphology via H. E staining was observed after
      the aorta was taken out from the rats executed by narcosis. VCAM mRNA were
      determined by in situ hybridization analysis. RESULTS: (1) Diabetes mellitus and
      aorta lesion occurred in the four model groups. (2) Puerarin could decrease the
      levels of cholesterol (P < 0.05), low density lipoprotein (P < 0.05), P-selectin
      (P < 0.05), oxidative low density lipoprotein, and glycosylated low density (P <
      0.05), lipoprotein increase high density lipoprotein (P < 0.05). The gene
      expression of VCAM in the aorta were significantly inhibited, and the action of
      Puerarin showed some dose reaction relationship at the same time (P < 0.05).
      CONCLUSION: Puerarin have a certain in preventing aorta by inhibiting expression
      of adhesion molecule.

PMID- 18095573
TI  - [Analysis of quality of life and its influence factors of elderly persons in
      urban in Chengdu].
AB  - OBJECTIVE: To investigate the quality of life of elderly persons in urban in
      Chengdu, and to identify the influence factors. METHODS: A survey with EQ-5D and
      questionnaire was undertaken in 378 randomly selected residents who were over 60
      years age in urban communities in Chengdu. Univariate and multivariate
      statistical methods were employed to analyze the data. RESULTS: The general
      evaluation on quality of life of elderly persons in urban in Chengdu was better.
      The average score of EQ-5D was 0.804. The evaluation of mobility, self-care and
      usual activities of elderly persons were better. The rates of satisfaction were
      80.3%, 93.3% and 86.6% respectively. The evaluation of body and emotion feeling
      was relatively poor. The rates of satisfaction were 47.1% and 79.1% respectively.
      The multivariate statistical analysis showed that the quality of life of elderly
      persons was influenced by chronic disease, age and education. The qualities of
      life of elderly persons who experiences of chronic disease, aging, lower
      education were debasement. CONCLUSION: The chronic disease was the mostly
      influence factor to quality of life of elderly persons in urban in Chengdu.

PMID- 18095574
TI  - [Case-control study of risk factors for community acquired pneumonia among old
      persons in Shanghai City].
AB  - OBJECTIVE: To explore the risk factors of community acquired pneumonia (CAP)
      among persons at the age of equal to or older than 65 years old in Shanghai City.
      METHODS: A case-control study was carried out to study the risk factors of CAP.
      Some of the CAP cases were recruited from the survey in Xinhua Community and
      Bansongyuan Community, others were from a hospital's outpatients. The controls
      were taken sample from the two communities. All the cases and controls were 65
      years old or above. The cases and controls were interviewed with a structured
      questionnaire. Multivariate non-conditional logistic regression and chi-square
      test were used to analyze the data. RESULTS: 128 cases and 306 controls were
      enrolled for the case-control study. Through the multivariate logistic
      regression, it was found that the risk of CAP was increased with regard to age
      (OR = 1.049, 95% CI 1.007-1.093), smoking (OR = 2.317, 95% CI 1.224-4.386), ADL
      score (OR = 0.599, 95% CI 0.474-0.755), chronic respiratory system diseases (OR =
      6.295, 95% CI 3.738-10.604) and non lung cancer (OR = 4.332, 95% CI 1.340
      14.005). CONCLUSION: Old age, smoking, lower ADL score, chronic respiratory
      system diseases and cancer may be the risk factors of CAP. The effective measures
      should be taken to prevent community acquired pneumonia of old persons with these
      characteristics.

PMID- 18095575
TI  - [Study on the quality of life and its impact factors of drug users with opiate
      dependence in three cities in Sichuan].
AB  - OBJECTIVE: To analyze the quality of life (QOL) of drug users with opiate
      dependence in 3 cities in Sichuan, find the impact factors of QOL, and provide
      some foundation for improving the QOL of this population. METHODS: The short form
      36 ( SF-36) and perceived social support scale (PSSS) were used to assess QOL and
      social support, respectively. A self-designed questionnaire that was utilized to
      investigate the general characteristics and factors related to drug dependence.
      The data were tested by the Student t test, correlated analysis, variance
      analysis, and linear stepwise multivariate regression. RESULTS: (1) The score of
      physical functioning, role-physical, body pain, general health, vitality, social
      functioning, role-emotional, mental health of opiate users were significantly
      lower than that of the control (P < 0.001). The social support of opiate users
      was significantly lower than the control when used the PSSS to evaluate various
      domain of social support (P < 0.001). (2) The univariate analysis showed that
      total 17 factors included age, marital status, education, occupation, economic
      income, smoking, chronic disease, 3 domains of social support, drug-taking
      manner, co-use syringe, drug-taking of family member, duration of drug-taking,
      dose of drug-taking, abstinence manner and relapse time were correlated with the
      all or part of the domains of the QOL. (3) The multivariate analysis indicated
      that the main factors involved in influenced the QOL of the opiate users were
      duration of drug-taking, dose of drug-taking, external social support of family,
      total social support, co-use syringe and economic income. Marital status,
      internal social support of family, drug-taking manner, chronic disease, smoking,
      drug-taking of family members, abstinence manner and relapse times had impacts on
      a few domains of the QOL. CONCLUSION: The QOL of opiate users in 3 cities in
      Sichuan was low and they were lack of enough social support.

PMID- 18095576
TI  - [Status of dietary calcium intake of Chinese residents].
AB  - OBJECTIVE: To describe the calcium intake of different age and gender residents
      in different area in China. METHODS: 68962 study' participants were came from
      23,470 households who were randomly selected from 132 counties in 31 provinces,
      autonomous regions and the municipalities in China. The 24-hour dietary recall
      method for 3 consecutive days was used to collect food intake information, except
      for the condiment intake, which was collected by weighting method. RESULTS: The
      average intakes of calcium were low in Chinese population. The average intake of
      calcium of male people were more higher than those of female people, while the
      intake level of urban residents were more higher than those of rural residents.
      The calcium intake of the most persons could reach 20%-60% of adequate intake
      (Al). Less than 5% person's calcium intake could reach AI. Only 1.1% to 1.7%
      adolescents aged 11 years to 13 years whose calcium intake level could reach AI.
      The main sources of calcium were vegetable, bean and bean product, wheat and
      rice, which provided 35.2%, 13.9%, 11.2% and 9.1% calcium respectively, only 4.3%
      calcium came from dairy products. CONCLUSION: The deficiency of calcium is a
      common problem in Chinese residents. In particular, the adolescents are the most
      serious group.

PMID- 18095577
TI  - [Sub-health condition of teachers of the middle school evaluated by two means in
      Nanchong City].
AB  - OBJECTIVE: To evaluate the sub-health condition of teachers of the middle
      schools. METHODS: The method of cluster random sampling trial was adopted. The
      sub-health condition was interviewed by the questionnaire made by ourselves, and
      was detected by multifunctional microscopy diagnostic instrument for 693 teachers
      in study group and 970 persons in control group. RESULTS: The results showed that
      the questionnaire could get a good reliability and validity. The results of
      questionnaire inspection were accordant with the multifunctional microscopy
      diagnostic instrument in evaluating sub-health condition. The incidences of sub
      health condition in study group were more higher (58.8%) than those in the
      control group (50.0%) (P < 0.05), and the incidences of sub-health condition in
      female teachers (60.9%) were more hither than those in male teachers(55.9%) (P <
      0.05), and the incidences of sub-health condition at the age of 30-45 years
      (73.0%) were more higher than those in any other ages (P < 0.05). CONCLUSION: The
      results indicated that teachers of the middle schools could easily suffer from
      sub-health condition.

PMID- 18095578
TI  - [Preventive effects of 4 Se-enriched plants on rat stomach cancer induced by MNNG
      -1. inhibitary effects of different selenium resources on rat aneuploid cell
      incidence in mucosal epithelium of gastric antrum].
AB  - OBJECTIVE: To obtain new Se resources with high healthy value (both high activity
      and low toxicity), the preventive efficacies of three Se-enriched higher plants
      on stomach cancer were compared with selenite and Se-enriched garlic. METHODS:
      Ninety weanling male Wistar rats were fed the basal diet for a week, divided
      equally into nine groups, control, MNNG,Se 75 and 150 microg/kg bw of selenite,
      Se 150 and 300 microg/kg bw of Se-enriched garlic, Se 150 microg/kg bw of Se
      enriched broccoli, Se 300 microg/kg bw of Se-enriched red kales and green kales
      group. Rats in MNNG and Se supplementation groups were daily given 15 mg/kg bw of
      MNNG (solved in 1 ml distilled water) and the rats of control group were given 1
      ml distilled water by gavage for ten days. Meanwhile, the rats of the control and
      MNNG group were daily given 1 ml distilled water and the rats of other groups
      were given 1 ml water suspension of Se-enriched garlic, red kavas, green kavas,
      broccoli or 1 ml solution of sodium selenite by gavage for seventeen weeks. All
      rats were freely fed the basal diet and water during the period of the
      experiment. At the end of 18th week, the rats were sacrificed, the incidence of
      aneuploid cells (IAC) in mucosal epithelium of the gastric antrum was detected,
      and the IAC data were analyzed by SPSS 12.0. RESULTS: The results showed that the
      IACs were 25% and 30%, respectively, in the Se 150 microg/kg bw of Se-enriched
      garlic and -broccoli group, and were in turn 22%, 50% and 30% in the 300
      microg/kg bw of Se-enriched garlic, -red kale and -green kale. No significant
      differences of IACs were found in the same level of Se supplementation groups by
      Se-enriched plants. CONCLUSION: The data showed that Se-enriched broccoli, red
      kale and green kale had high activities similar to Se-enriched garlic in stomach
      cancer prevention and lower toxicity than selenite.

PMID- 18095579
TI  - [Adhesion and inhibiting adhesion of Helicobacter pylori to SGC-7901 cell in
      vitro by four Lactobacilli from human].
AB  - OBJECTIVE: To investigate the adherence ability of four Lactobacilli to gastric
      epithelial cell SGC-7901 and the ability of inhibiting the adherence of
      Helicobacter pylori to the cells. METHODS: The light microscope and scanning
      electron microscope were used to detect Lactobacilli that adhering to SGC-7901
      cells after co-culturing for 2 hours. Using FITC-conjuncted antibody, the adhered
      Helicobacter pylori density was evaluated under fluorescence microscope after
      pretreatment with live or nonviable Lactobacilli. RESULTS: Four Lactobacilli's
      live and nonviable stains could adhere to SGC-7901 tightly and obviously inhibit
      the adherence of Helicobacter pylori, but their adherence ability was not
      different, excluding their live stains adherence ability. And their inhibiting
      ability were different, of which the best was Lac15, the worst was Lac12.
      CONCLUSION: Four Lactobacilli can inhibit the adherence of Helicobacter pylori to
      gastric epithelial cell SGC-7901 in vitro, and they should be further evaluated
      in vivo.

PMID- 18095580
TI  - [Nitric oxide and nitric oxide synthase related to male reproduction].
AB  - Nitric oxide (NO) may be a kind of signal molecule which may have multiplicate
      physiological function such as secondary messenger, neurotransmitter and effect
      molecule. NO may play a crucial role in organism. The production of NO can not
      get away from nitric oxide synthase (NOS) which may distribute in almost all kind
      of organs of male reproductive system. NO and NOS may have the function of
      bifunctional regulation for reproduction. In this paper, the regulatory function
      of NO and NOS on male reproductive system were reviewed.

PMID- 18095581
TI  - [Potential toxicities of flavonoids].
AB  - Flavonoids may be natural components came from many vegetables and fruits. A
      variety of heath effects of these compounds were found. However, a few safety
      studies indicated that certain adverse effects of these compounds could influence
      on human health, which could involve genotoxic/carcinogenic effects or
      interaction with thyroid hormone biosynthesis. Isoflavones' estrogenic activity
      could influence on sexual development of young animals and children. Furthermore,
      flavonoids could inhibit the absorption of some nutrients, interact with certain
      drug pharmacokinetics and affect neurobehavioral development. In this paper, the
      potential toxicities of flavonoids from recently published papers were reviewed.

PMID- 18095582
TI  - [Effects of soybean isoflavones on relieving menopausal syndrome and
      osteoporosis].
AB  - Soybean isoflavones are one kind of natural phytoestrogens. As it may have
      estrogen-like biological activities and no obvious side effects. Soybean
      isoflavones should be paid attention. It has been shown that soybean isoflavones
      could play an important role in reducing the risk of cardiovascular disease, some
      kind of cancers, osteoporosis and alleviating menopausal syndrome. Their effects
      of soybean isoflavones on menopausal syndrome and osteoporosis were reviewed in
      this paper.

PMID- 18095583
TI  - [A review on the determination of quinolones residues in edible animal tissue--I
      pretreatment methods].
AB  - In this paper, the methods which described for the determination of quinolone
      residues in edible animal tissues at home and abroad from 2000.1 to 2006.9 were
      reviewed. The methods of sample handling were discussed. And a summary of the
      most relevant information about the analytical procedures was included.

PMID- 18095584
TI  - [Progress of intervention programs that providing care and support for children
      affected by HIV/AIDS].
AB  - Intervention programs that provide care and support for children affected by
      HIV/AIDS should follow the five strategies suggested by UNICEF/UNAIDS, focusing
      on nutrition and health services, education, psychology issues and economic
      support. Participatory monitoring and evaluation method should be employed in the
      evaluation process to encourage the participation of children. Suggestions are
      made to explore issues on the population size of children affected, factors
      influencing children's health, intervention models and evaluation indicators on
      children's health.

PMID- 18095585
TI  - [Construction of recombinant adenovirus vector for RNA interference with
      multidrug resistance MDR1 gene].
AB  - OBJECTIVE: To construct the recombinant adenoviral RNA interference (RNAi) vector
      in order to inhibit the expression of multidrug resistance MDR1 gene, and probe
      whether gene therapy for multidrug resistance of epilepsy is feasibility.
      METHODS: Three target sequences for short hairpin RNA (shRNA) expression were
      selected and designed according to MDR1 gene sequence of rat. Annealed oligos
      were inserted into the downstream of treated pSIREN-shuttle U6 promoter to
      construct RNAi plasmid pSIREN-shuttle-MDR1. Next, MDR1 shRNA sequence was cloned
      to pAdeno-X, a transfer vector of adenovirus, to produce the pAdeno-MDR1, which
      was then packed and amplified in HEK293 cells. Further the recombinant adenovirus
      was purified by CsCl and used to infect the rat astrocytes with P170-glucoprotein
      (P-gp) over-expression which have been induced by coriaria lactone (CL). RESULTS:
      It was confirmed by restriction digestion, PCR and sequencing that MDR1 shRNA
      expression structure was correctly cloned to pSIREN-shuttle and pAdeno-X vector
      respectively. Virus titer was 6 x 10(9) pfu/mL. The interference efficiency of
      pAdeno-MDR1 to the expression drop of multidrug resistance gene in astrocyte
      model neared to 100%. CONCLUSION: RNAi adenovirus vector of rat MDR1 gene has
      been constructed and found its high interference efficiency. It is the essential
      building required for the remedy of refractory epilepsy and the research on
      mechanism of multidrug resistance.

PMID- 18095586
TI  - [Explorative study on mechanism and drug intervention for chronic allograft
      nephropathy induced by renal ischemia-reperfusion injury].
AB  - OBJECTIVE: This study is aiming to investigate the mechanism and drug
      intervention of chronic allograft nephropathy (CAN) induced by renal ischemia
      reperfusion injury. METHODS: The closed colony strain Sprague-Dawley (SD) and
      Wistar Rats were used as donor and recipient, respectively. Orthotopic kidney
      transplantation was performed following the procedure of our previous study. The
      rats were divided into five groups: Group A only received CsA with 10 mg/(kg x
      d); except CsA, Group B,C,D received Yi Sheng injection with 4 mg/(kg x d), 8
      mg/(kg x d), and MMF (20 mg/(kg x d)], respectively. Group E was control group.
      According to Banff standard, the serum creatinine (SCr) level and pathological
      change of rat grafted kidney were observed at the 4th, 8th and 12th weeks post
      transplantation. The immunohistochemistry and real-time fluorescence quantitative
      polymerase chain reaction were used to comprehend the localization and expression
      of TGFbeta1 and Smad2, 7 in the transplant kidney. RESULTS: Compared with the
      lower dosage group, the differences of SCr level and pathological changes of CAN
      at all the time points after 8th week were statistically significant in the high
      dosage Yi Sheng group. It was showed that the Yi Sheng injection had the
      protective effect on CAN with a dose-dependent fashion. After transplantation,
      the rat kidney-sclerosis model showed that the up-regulated expressions of TGF-P,
      and Smad2 and the down-regulated expression of Smad7 in Group A and Group B were
      statistically significant, which meant that the difference was obvious when Group
      A compared with the other 4 groups. The expressions of TGF-beta1, and Smad2 were
      strongly positive in tubular epithelial cell, interstitial cell and glomerulus,
      while the expression of Smad7 was weak. Thickening of endovascular could
      significantly be inhibited in high dosage of Yi Sheng and MMF group. CONCLUSION:
      The up-regulated expressions of TGF-beta1 and Smad2 and the down-regulated
      expression of Smad7 may accelerate the progression of CAN alone or with immune
      factors. The traditional Chinese medicine Yi Sheng injection and MMF can down
      regulate the expression of TGF-beta1 and Smad2 and block the down-regulated
      expression of Smad7, which may postpone and lessen the progression of CAN.

PMID- 18095587
TI  - [The study in lasting effectivity on conditionally replicating adenovirus shRNA
      mediating survivin gene silencing in colon carcinoma cell line HT-29].
AB  - OBJECTIVE: To investigate the lasting effect of conditionally replicating
      adenovirus shRNA on survivin gene silencing in colon carcinoma cell lineHT-29.
      METHODS: We transfected the colon cancer HT-29 cell with Ad-delE1b55KD
      shRNA/Survivin-EGFP (control shRNA vector was the replication defective
      adenovirus called as Ad-shRNA/Survivin-EGFP). The expressions of EGFP, survivin
      mRNA and protein in HT-29 were detected at 1st day, 7th day, 14th day and 28th
      day after cell transfection. RESULTS: The expression of EGFP in HT-29 was high at
      7th day after cell transfection but survivin mRNA and protein expressions
      inhibited in each experiment group, among which Ad-delE1b55KD-shRNA/Survivin-EGFP
      group showed the most high EGFP expression; at 14th day, the expression of EGFP
      went down but the survivin mRNA and protein expressions upregulated obviously in
      replication defective adenovirus group and liposome vector group, however EGPF
      expression in HT-29 cell was still high and the survivin mRNA and protein
      expressions were still inhibited in Ad-delE1b55KD-shRNA/Survivin-EGFP group; at
      28th day after cell HT-29 transfected, the expression of EGPF and the expression
      inhibition of survivin mRNA and protein disappeared in Ad-shRNA/Survivin-EGFP and
      liposome groups, but it was not in Ad-delE1b55KD-shRNA/Survivin-EGFP group (P <
      0.05). CONCLUSION: Conditionally replicating adenovirus shRNA can mediate the
      survivin gene silencing with long-lasting effects on colon carcinoma cell lines
      HT-29.

PMID- 18095588
TI  - [Construction and expression of recombinant plasmid pcDNA3.1(+) -hHGF available
      in osteoblast].
AB  - OBJECTIVE: To construct a plasmid carrying human hepatocyte growth factor (hHGF)
      gene and determine the effects of the hepatocyte growth factor (HGF) gene on
      proliferation and differentiation of osteoblast in vitro. METHODS: The full
      length cDNA of hHGF, which was amplified from human liver mRNA by RT-PCR, was
      cloned into pcDNA3.1(+) vector to construct pcDNA3.1(+) -hHGF recombinant
      plasmid. With lipofectamine, the recombinant plasmid pcDNA3.1(+) -hHGF was used
      to transfect the culture osteoblasts. After pcDNA3.1(+) - hHGF transfection, the
      positive cell clones were selected with G418. The stable transfection and
      expression of hHGF in the osteoblasts were measured by immunohistochemical
      staining and RT-PCR respectively. The effect of pcDNA3.1(+) -hHGF transfection on
      osteoblast proliferation was measured by MTT colorimetric assay. Flow cytometer
      was used to determine the effect of pcDNA3.1(+) -hHGF transfection on cell cycle
      of osteoblast. The quantitive detection of hHGF expression was performed through
      ELISA. Alkaline phosphatase (AP) was also detected using enzyme kinetics.
      RESULTS: The recombinant plasmid pcDNA3. 1(+) -hHGF was identified by restriction
      endonuclease digestion and nucleotide sequencing. Osteoblasts could be
      effectively transfected by pcDNA3.1(+) -hHGF with lipofectamine in vitro. The
      stable expression of hHGF in pcDNA3.1(+) -hHGF transfection osteoblast was
      confirmed. Human HGF protein was detected by immunohistochemical staining and RT
      PCR in osteoblasts 4 weeks after cell clone selected with G418. pcDNA3.1(+) -hHGF
      gene transfer responsible to improve the proliferation was proved by MTT assay,
      flow cytometer showed cellular proportion in "S" phase obviously increased. AP
      activity in transfected cells was increased significantly. CONCLUSIONS:
      Osteoblasts which express stable and high-level hHGF was established
      successfully, exogenous hHGF gene could stimulate the proliferation,
      differentiation and function of osteoblast and could be applied further to gene
      therapy.

PMID- 18095589
TI  - [Signaling pathway of BDNF protecting embryonic cortical neurons from hypoxia].
AB  - OBJECTIVE: To investigate the changes of TrkB and Ras-MAPK in brain-derived
      neurotrophic factor (BDNF) protecting the embryonic rat cerebral cortical neurons
      against hypoxia-induced neurotoxicity. METHODS: The immunofluorescence technique,
      laser scanning confocal microscope and half-quantitative analysis were done to
      explore the changes of the intracellular levels of tyrosine kinase B (TrkB),
      phosphorylated TrkB and the mitogen-activated protein kinase (MAPK) in rat
      embryonic cortical neurons cultured in different time groups of hypoxia with or
      without BDNF pretreatment. RESULTS: The fluorescent intensity of TrkB and
      phosphorylated TrkB in the cytoplasm and the fluorescent intensity of MAPK in
      both cytoplasm and cell nucleus of the neurons were significantly increased in
      the presence of BDNF (P < 0.05), the fluorescent intensity of neurons pretreated
      with BDNF 24 h before the hypoxia culture was stronger than those with BDNF just
      before the hypoxia culture (P < 0.05). CONCLUSION: The Ras-MAPK approach may be
      the major signal transferring way of BDNF in protecting the cortical neurons from
      hypoxia-induced neurotoxicity. The approach of signal transferring begins with
      tyrosine phosphorylation of TrkB receptors.

PMID- 18095590
TI  - [The influence of oxygen and glucose deprivation on the expression of neurite
      growth inhibitor Nogo-A in oligodendrocyte precursor cell of rat].
AB  - OBJECTIVE: To investigate the Nogo-A expression and its regeneration inhibition
      role in oligodendrocyte precursor cells (OLPs) after oxygen & glucose deprivation
      (OGD). METHODS: The OLPs were separated by the improved procedure of separation
      and purification through agitation and then cultured in chemically defined
      medium. The OGD model of OLPs was set up by using Na2S2O4 and Earle's fluid in
      the medium in vitro. Immunofluorescence assay was applied to identify the OLPs
      with its specific antibodies such as A2B5, O4 and O1. Western blot and
      immunofluorescence assay were used to analyze the expression of Nogo-A in OLPs at
      10 min, 30 min and 60 min after OGD. The livability rate of cells in each group
      was detected by MTT. RESULTS: The expression of Nogo-A was increased
      significantly compared with control at 10 min, 30 min and 60 min after OGD (P <
      0.05). MTT result showed that the livability rate of OLPs with OGD was
      significantly lower than that of control (P < 0.05). CONCLUSION: The expression
      of Nogo-A is increased while the OLPs livability is dropping down after OGD,
      which suggests that Nogo-A may play a role in OLPs damage and in the pathogenesis
      of restraining OLPs' regeneration.

PMID- 18095591
TI  - [Expression of chemokine receptor CCR2 in cerebral tissue of newborn rat with
      experimental hypoxic-ischemic brain damage].
AB  - OBJECTIVE: To observe the expressions of mRNA and protein for the CCR2 in
      cerebral tissue with experimental hypoxic-ischemic brain damage (HIBD) to newborn
      rat. METHODS: The HIBD model of SD rat was set up by ligating the right carotid
      artery and exposing the animals to 8% oxygen for 2.5 h. The dynamic change of
      CCR2 mRNA level was studied by using quantitative, real-time, fluorescence PCR
      assay (TaqMan), and the change of CCR2 protein was detected by SDS-PAGE assay.
      RESULTS: The highest expression of CCR2 mRNA was showing at 24 h after HIBD, of
      which the level was significantly higher in hypoxic-ischemic (HI) cerebral
      hemisphere than in control (P < 0.05). The CCR2 mRNA level of 72 h after HIBD was
      still higher than that of control (P > 0.05) but had no difference on 7 d after
      HIBD when compared with control (P > 0.05). The increased expression of CCR2
      protein was detected at 12 h after HIBD and peaked at 24 h after HIBD. The
      significant increase of CCR2 protein persisted in HI hemisphere up to 3 d after
      HIBD. CONCLUSION: The expressions of CCR2 mRNA and protein increase significantly
      in cerebral tissue of newborn rat with HIBD. The dynamic change of CCR2
      expression is consistent with the process of HIBD, which suggests that CCR2
      expression after HIBD may play an important role in the mechanism of brain
      damage.

PMID- 18095592
TI  - [The study about immune response to Balb/c mice inoculated with hepatitis B virus
      DNA vaccine pCI/S2S].
AB  - OBJECTIVE: To construct the hepatitis B virus (HBV) DNA vaccine pCI/S2S, and
      study the expression of specific antigen protein in muscle tissue section and the
      specific immune responses of humoral and cellular immunity in BALB/c mice being
      inoculated with pCI/S2S. METHODS: DNA templates were acquired from the mixed
      serum of patients with chronic hepatitis B, and the gene fragment S2S of HBV was
      cloned. The pCI vector and DNA S2S fragment were doubly cut by Kpn I and Not I,
      and then linked. HBV DNA vaccine pCI/S2S were intramuscularly injected into
      BALB/c mice, and boosted after 4 and 8 week. The expressing protein product in
      muscle tissue in situ and the specific cellular immune response were detected in
      12 week after the first injection, the specific humoral immune responses were
      detected at 1, 2, 4, 6, 8, 12 week after the first injection. RESULTS: After
      pCI/S2S intramuscularly injected into BALB/c mice, HBsAb and preS2Ab were
      gradually determined with cytotoxic T lymphocyte responses induced, and HBsAg
      protein was expressed in situ in muscle tissue. CONCLUSION: pCI/S2S is effective
      HBV DNA vaccine that can induce the specific humoral and cellular immune
      responses.

PMID- 18095593
TI  - [Interrelationship between change of cAMP responsive element binding protein
      (CREB) or N-methyl-D-aspartate receptor (NR1) expressing in hippocampus and
      impairment of learning and memory after epilepsy].
AB  - OBJECTIVE: The changes of transcription factors CREB and glutamate receptor N
      methyl-D-aspartate (NMDA) receptor subtype NR1 expressing in hippocampus and the
      relationship between CREB or NR1 expression change and learning or memory deficit
      after epilepsy. Exploring the role of CREB and NR1 in impairment of cognitive
      function after epilepsy. METHODS: Status epilepticus (SE) and chronic epilepsy
      (CEP) rats were kindled by using pentylenetetrazol (PTZ) as the convulsant. The
      function changes of learning and memory in different types of epileptic model
      rats were examined by alternative electro-stimulus Y-maze test. RT-PCR detection
      was used to analyze NR1 and CREB mRNA expression in hippocampus tissues.
      Immunocytochemistry technique was used to analyze CREB protein (pCREB) expression
      in hippocampus tissue. RESULTS: The results of alternative electro-stimulus Y
      maze test (AESYT) showed that the total error (TE) in SE rats were higher than
      corresponding control rats at 1 d and 10 d after epilepsy (P < 0.05), there were
      no difference at 30 d after epilepsy (P > 0.05); In CEP rats, the TE in AESYT
      were higher than corresponding control rats at 1 d, 10 d and 30 d after epilepsy
      (P < 0.05). It was showed that expression of NR1 mRNA in hippocampus was
      significantly decreased in SE group and CEP group (P < 0.05) comparing with
      corresponding control group at 24 h after epilepsy, there were no significant
      difference between any two groups at 30 d after epilepsy (P > 0.05). The
      expression of CREB mRNA in hippocampus was significantly decreased in SE group (P
      < 0.05) at 24 h after epilepsy, and there was no significant difference in CEP
      group. At 30 d after epilepsy, the expression of CREB mRNA was decreased only in
      CEP group, but no difference in SE group. It was observed that pCREB positive
      neurons were distributed in CA1, CA3 and DG of rat hippocampus. The expression of
      pCREB positive cellular nucleus significantly decreased in SE group and CEP group
      comparing with control group at 24 h after epilepsy. CONCLUSION: The change of
      learning and memory after epilepsy is related to the expression of NR1 and CREB
      in hippocampus. The epilepsy seizures to SE and CEP rats could result in the
      impairment of learning and memory, and be followed by the decreases in expression
      of NR1 and CREB mRNA and level of CREB protein. It shows that NR1 and CREB may be
      involved in the pathophysiological process of learning and memory deficit.

PMID- 18095594
TI  - [The influence of angiotensin II receptor blockade on the expressions of Col I
      and TIMP-1 mRNA in cardiac fibroblast of adult rat].
AB  - OBJECTIVE: To investigate the role of angiotensin II receptor type 2 (AT2) on
      collagen metabolism in cardiac fibroblast, and the difference between AT2 and
      angiotensin II receptors type 1 (AT1). METHODS: Adult rat cardiac fibroblasts
      were isolated and cultured. The cells were divided into 4 groups: Angiotensin II
      (Ang II), Ang II + Losartan, Ang II + PD123319, Ang II + Losartan + PD123319.
      Semiquantitative reverse transcription PCR was used to determine the mRNA levels
      of collagen I (Col I ) and tissue inhibitor of metalloproteinase 1 (TIMP-1).
      RESULTS: Losartan-treatment making AT1 blockade decreased Col I mRNA to 71.8% in
      cardiac fibroblasts, AT2 blockade from PD123319-treatment decreased Col I mRNA to
      81.5%, co-treatment of both AT1 and AT2 blockade decreased Col I mRNA to 50.9% ;
      the AT1 blockade with Losartan-treatment decreased TIMP-1 mRNA to 88.1% in
      cardiac fibroblasts, AT2 blockade by PD123319-treatment decreased TIMP-1 mRNA to
      75.4%, Both AT1 and AT2 blockade by co-treatment decreased TIMP-1 mRNA to 44.1%.
      CONCLUSION: AT2 receptor is involved in collagen metabolism in cardiac fibroblast
      by regulating the levels of Col I and TIMP-1 mRNA.

PMID- 18095595
TI  - [Effect of lycopene on the proliferation of MCF-7 and MDA-MB-231 cells].
AB  - OBJECTIVE: To test the effect of lycopene on the proliferation and apoptosis of
      the estrogen receptor(ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast
      cancer cell lines. METHODS: The cell proliferation was analyzed by the MTT and
      the H3-TdR incorporation. The effect of lycopene on the cell cycle and apoptosis
      of the synchronized cells was observed through flow cytometry. RESULTS: Lycopene
      inhibited the growth and DNA synthesis of both ER-positive MCF-7 and ER-negative
      MDA-MB-231 cells in a dose-dependent pattern. The maximum inhibition effect
      appeared after 4 days of exposure to lycopene, with an inhibition rate of 52.6%
      and 61.9% for the MCF-7 and MDA-MB-231 cells respectively. The flow cytometry
      analysis found more cells in the G0/G1 phase and less cells in the S and G2/M
      phase after 24 hours of exposure to lycopene. Lycopene induced apoptosis for the
      MDA-MB-231 cells, but not for the MCF-7 cells. CONCLUSION: Lycopene inhibits the
      growth of ER-positive MCF-7 cells through the inhibition of the cell cycle
      progression. The inhibition of ER- negative MDA-MB-231 cells by lycopene is
      associated not only with the G1 phase cell cycle-arrest but also the induction of
      apoptosis.

PMID- 18095596
TI  - [Inhibitory effect of isorhamnetin and hesperidin on the oxidation of high
      density lipoproteins (HDL) induced by Cu2+].
AB  - OBJECTIVE: To test the inhibitory effect of isorhamnetin and hesperidin on the
      HDL oxidation induced by Cu2+. METHODS: The serum HDL was isolated by the one
      step density gradient ultracentrifugation. The HDL oxidation was induced by Cu2+
      in vitro for different length of periods. Isorhamnetin and hesperidin at 5
      micromol/L, respectively, were added 3 h before the copper oxidation. The
      oxidation of HDL was measured by the levels of absorbance at 234 nm (A234),
      relative electrophoretic mobility (REM), thiobarbituric acid reactive substances
      (TBARS) and protein carbonyls content. RESULTS: (1) A234, REM, TBARS and protein
      carbonyls formation increased gradually after 2, 4, 6, 8, 12 and 24 h of HDL
      oxidation induced by CU2+ without treatment with isorhamnetin or hesperidin. (2)
      With the treatment of isorhamnetin or hesperidin, the kinetic changes of A234,
      REM, TBARS and protein carbonyls formation delayed 2-6 h and 2-4 h, respectively.
      Compared with the controls, the A234, REM, TBARS and protein carbonyls formation
      were reduced by 16.3%-46.9% (P < 0.001), 0.6%-25.2% (P < 0.05), 9.2%-28.4% (P <
      0.01) and 11.6%-45.2% (P < 0.001) by isorhamnetin and by 1.5%-30.0%, 1.4%-13.3%,
      6.6%-18.8% (P < 0.05) and 14.4%-62.0% (P < 0.001) by hesperidin, respectively.
      CONCLUSION: Both isorhamnetin and hesperidin inhibit the oxidation of HDL, but
      isorhamnetin functions stronger.

PMID- 18095597
TI  - [Gene expressions of xylosyltransferase and heparanase in renal tissue of rat
      with adriamycin nephropathy and relevance for proteinuria].
AB  - OBJECTIVE: To evaluate the roles of P-D-xylosyltransferase I (XT-I) and beta-D
      endoglycosidase heparanase (Hpa) in renal tissue with the development of
      adriamycin (ADR) nephropathy and relevance for proteinuria. METHODS: 150-200 g
      Sprague-Dawley rats (n=10 per group) were used to make the nephropathy model
      induced by tail intravenous injection of 6 mg/kg ADR. Rats were housed in
      metabolic cage for 24 hours so as to collect the urine prior to disease induced
      and at day 7, 14 and 21 following disease induction. By using the method of
      reverse transcriptase-PCR (RT-PCR), XT- I and Hpa genes from renal tissue of
      these groups were assayed respectively. RESULTS: (1) Rats with nephropathy at day
      7, 14 and 21 showed the marked up-regulated XT- I mRNA and the significant
      difference in contrast to the normal rats,and rats at day 21 showed the marked up
      regulated XT- I mRNA and significant difference in contrast to nephropathy rats
      at day 7. There was a positive linear correlation between the expression level of
      XT- I mRNA from the renal tissue of nephropathy rats and the quantity of urinary
      protein (r = 0.760, P < 0.05). (2) The nephropathy rats at day 7, 14 and 21
      showed marked up-regulated Hpa mRNA and significant difference in contrast to the
      normal rats,the rats at day 14 and 21 showed marked up-regulated Hpa mRNA and
      significant difference in contrast to the rats at day 7. There was a positive
      linear correlation between the expression level of Hpa mRNA from renal tissue and
      quantity of rat urinary protein (r = 0.757, P < 0.05). CONCLUSION: The up
      regulated expressions of XT- I and Hpa mRNA in rat renal tissue exist in
      Adriamycin nephropathy. Higher Hpa mRNA expression, more quantity of urinary
      protein;more quantity of urinary protein,higher XT-I mRNA expression.

PMID- 18095598
TI  - [Respiratory virus expression in renal tissues and urine of children with steroid
      responsive simple nephrotic syndrome].
AB  - OBJECTIVE: To explore the relationship between respiratory virus infection and
      the episode of steroid responsive simple nephrotic syndrome (SRSNS). METHODS:
      Thirty eight children with SRSNS were recruited (28 in the active stage, 10 in
      the remission stage). Sixty four children (18 with nephritic nephrosis, 16 with
      bronchiolitis, 15 with secondary glomerular diseases and 15 without diagnosed
      diseases) served as controls. Reverse transcriptase-PCR (RT-PCR) and alkaline
      phosphoesterase-anti alkaline phosphoesterase enzyme-linked assay (APAAP) were
      employed to detect the viral genes and antigens in the urines respectively. The
      viral antigens in the renal tissues of two children with active SRSNS were also
      examined by APAAP. RESULTS: The viruses were more often detected in the urines of
      children with active SRSNS than those with remission SRSNS and the controls. The
      respiratory syncytial virus (RSV) was the most common virus detected in the
      urines of children with active SRSNS. The appearance of the viruses gene and
      antigens was not influenced by the use of steroid. The same antigens were found
      in the renal tissues of the two children with active SRSNS. CONCLUSION:
      Respiratory tract viruses may play an important role of triggering the SRSNS.

PMID- 18095599
TI  - [Fentanyl hypnotic interaction with emulsified isoflurane].
AB  - OBJECTIVES: To explore the effect of fentanyl on 50% effective dose (ED50) of
      emulsified isoflurane for hypnosis and to define the type of interaction between
      fentanyl and emulsified isoflurane during rat hypnosis. METHODS: 125 male adult
      Sprague-Dawley rats (240-300 g) were divided into 5 groups depending on the drugs
      administered via the tail vein. The up-and-down sequential allocation technique
      was used to determine ED50 of fentanyl in the loss of righting reflex. According
      to above experiment results, the up-and-down sequential allocation technique was
      also used to determine ED50 of emulsified isoflurane combined with different
      fentanyl dose of 7.2 microg/kg (1/4 ED50), 14.3 microg/kg (1/2 ED50) or 21.5
      microg/kg (3/4 ED50), respectively, and also without the fentanyl in the loss of
      righting reflex. Fentanyl was administered intravenously for 20 s followed by
      emulsified isoflurane for 10 s. The interval between the two was 1.5 min in
      groups administered with both. ED50 was calculated by using Dixon-Mood method.
      The isobolographic and algebraic analyses were used to define the type of
      interaction between fentanyl and emulsified isoflurane. RESULTS: The body weight
      and sex of rats was not significantly different between the 5 groups. ED50 was
      (28.7 +/- 2.1) microg/kg (26.5-30.8 microg/kg) in the fentanyl group, (0.525 +/-
      0.032) mL/kg in the fentanyl 7.2 microg/kg +/- isoflurane group, (0.108 +/-
      0.019) mL/kg in the fentanyl 14.3 microg/kg+isoflurane group, (0.075 +/- 0.011)
      mL/kg in the fentanyl 21.5 microg/kg+isoflurane group and (0.670 +/- 0.054) mL/kg
      in the isoflurane group. The isobolographic analysis indicated that ED50 of
      isoflurane decreased progressively in a non-linear fashion in the presence of
      increasing dose of fentanyl. The isobolographic and algebraic analyses
      demonstrated that the combination use of fentanyl and emulsified isoflurane could
      produce a synergistic effect on hypnosis. CONCLUSIONS: Fentanyl enhances the
      hypnotic effect induced by emulsified isoflurane. The administration of
      associating fentanyl with emulsified isoflurane produces a synergistic effect on
      rat hypnosis.

PMID- 18095600
TI  - [Platelet autoantibody and its impact on platelet in patients with idiopathic
      thrombocytopenic purpura].
AB  - OBJECTIVE: To detect the platelet autoantibody in the patients with idiopathic
      thrombocytopenic purpura (ITP) and to investigate the impact of the autoantibody
      on the count and function of platelet. METHODS: The glycoprotein specific
      autoantibody was measured by MAIPA in the ITP patients, non-ITP patients and
      healthy people. The serum of the ITP patients were added to the healthy plasma
      with rich platelet and the platelet aggregation function was measured. RESULTS:
      The platelet autoantibody was found in 65.4% of the ITP patients. The platelet
      counts in the ITP patients with positive autoantibody were significantly lower
      than those without the autoantibody. The platelet counts were negatively
      correlated with the levels of the autoantibody, with a correlation coefficient of
      -0.724 for the anti GP IIb/ IIIa autoantibody and -0.571 for the anti GP Ib/ IX
      autoantibody. The aggregation of normal platelets was inhibited in ten out of the
      26 patients, among whom nine had platelet autoantibody. CONCLUSION: The platelet
      autoantibody affects not only the count but also the function of platelet.

PMID- 18095601
TI  - [Impact of controlled ovarian hyperstimulation delayed, which occurs after
      functionally pituitary downregulation by depot GnRH agonist, on the outcome of in
      vitro fertilization and embryo transfer].
AB  - OBJECTIVE: This study observed the influence on hormone, embryos and clinical
      outcomes when the starting time of controlled ovarian hyperstimulation (COH) was
      delayed after applying a half-dose depot gonadotropin-releasing hormone agonist
      (GnRHa). METHODS: A total 207 cycles were divided into 3 groups: control group
      (98 cycles, which performed daily low dose GnRHa during the mid-luteal phase in
      patients' menstrual cycles and reduced the dosage to a half at the next day 3,
      and added gonadotropin (Gn), conventional group (63 cycles, in which pituitary
      desensitization was obtained with a half-dose depot GnRHa in the mid-luteal
      phase, and then Gn was added at day 3) and delayed group (46 cycles, having the
      same usage of GnRHa to conventional group, but not adding Gn until day 7).
      RESULTS: The cancellation rate of cycle in conventional group was the highest (P
      < 0.01). At the beginning of COH, serum E2 and LH levels in delayed and control
      group were significantly higher than those in conventional group (P < 0.01). On
      the day of HCG given, serum E2 level in control group was the highest (P < 0.05).
      LH level in delayed and control group was higher than that in conventional group
      (P < 0.01). Concerning the clinical efficacy and outcome, the numbers of Gn
      ampoules and periods for stimulation were less in delayed group than in
      conventional group; the numbers of retrieved and fertilized oocytes, numbers of
      good quality embryos, clinical pregnancy rate and embryo implantation rate in
      delayed and control groups were significantly more than those in conventional
      group (P < 0.01). In ICSI cycles, the numbers of retrieved oocytes and metaphase
      II oocytes in delayed and control group were more than those in conventional
      group. CONCLUSIONS: A half-dose depot GnRHa may produce over suppression to
      pituitary gland in fertilization in vitro, appropriate delay of COH starting time
      can decrease ovarian stimulation period and ampoules of Gn, and increase
      retrieved good quality oocytes, so we could achieve a larger number of good
      quality embryos with a good chance of implantation.

PMID- 18095602
TI  - [Gene polymorphism of tumor necrosis factor-alpha promoter region in -308 site
      and premature births in Chinese Han populations].
AB  - OBJECTIVE: To investigate the relationship between the polymorphism of tumor
      necrosis factor-alpha gene--308G/A and premature births. METHODS: DNA was
      extracted from the blood samples taken from 96 women using chelex-100 method,
      among whom 46 gave premature births and 50 gave normal births. Then PCR-RFLP was
      performed to determine the TNF-alpha-308 gene polymorphism. RESULTS: (1) The
      frequencies of TNF-alpha -308 genotype TNF1/1 (GG) and TNF1/2 + TNF2/2 (GA + AA)
      were 60.9% and 32.6% +/- 6.5% for the women given premature births and 82.0% and
      12.0% + 6.0% for the women given normal births, respectively. The allele
      frequencies of TNF1(G) and TNF2(A) were 77.2% and 22.8% for the women given
      premature births and 88.0% and 12.0% for the women given normal births,
      respectively. The differences were statistically significant (P < 0.05). (2) The
      women with genotype TNF1/2(GA) and TNF2/2(AA) were 2.929 (95% CI 1.152-7.447)
      times of those with TNF1/1(GG) in risk of giving premature births. The women with
      allele (TNF2) were also more likely to give premature births, with an odds ratio
      (OR) of 2.169 (95% CI 0.999, 4.709) compared to those with TNF1. CONCLUSION: Gene
      polymorphism of Tumor Necrosis Factor-alpha promoter region in--308 site is
      associated with increased risk of premature births. TNF2(A) allele may be a risk
      factor of premature births in Chinese populations.

PMID- 18095603
TI  - [Multivariate analysis of impacting perinatal outcomes in preeclampsia].
AB  - OBJECTIVE: To discuss the influencing factors of perinatal outcomes in
      preeclampsia. METHODS: Statistically the single factor analysis and multivariate
      logistic regression analysis were performed for 448 preeclamptic women. RESULTS:
      There were 94 cases (21.0%) with had perinatal outcomes in 448 preeclamptic
      women, among which there were 41 perinatal death cases (9.2%). Single analyses
      showed that Onset gestation weeks, labor gestation weeks, subjective symptoms,
      convulsion, proteinuria degrees, edema, systolic pressure, diastolic pressure,
      white blood count, granulocyte count, urine protein quantity, plasma-albumin,
      lactate dehydrogenase, creatinine, antenatal care frequencies, hypertension
      (gestation weeks) and edema (gestation weeks) were correlated to bad perinatal
      Outcomes (P < 0.05). The logistic regression screened out such factors as labor
      gestation weeks (OR 0.583, 95% CI: 0.367-0.926), subjective symptoms (OR 9.315,
      95% CI: 1.500-57.833) and proteinuria degrees (OR 3.394, 95% CI: 1.226-9.397),
      which would influence perinatal outcome in preeclampais. CONCLUSION: Regular
      antenatal cares and extending gestation weeks may improve the perinatal Outcome
      in preeclampais.

PMID- 18095604
TI  - [Genetic polymorphism of interleukin-2 gene in Chinese Han and Thai populations].
AB  - OBJECTIVE: To investigate the polymorphisms of interleukin-2 (IL-2) gene at
      position -330 in the promoter region and +114 in the first exon, and to study the
      polymorphism distribution difference between the Chinese Han and Thai ethnic
      groups. METHODS: Using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method, authors detected the single nucleotide
      polymorphisms at position -330T/G and +114G/T in IL-2 genes of 130 healthy
      Chinese Han and 105 healthy Thai individuals. RESULTS: The frequency of TT
      genotype in IL-2 gene at position -330 was 36.9% in Chinese Han or 40.9% in Thai
      population. The frequency of TG genotype was 53.9% in Chinese Han or 39.1% in
      Thai population. The frequency of GG genotype was 9.2% in Chinese Han or 20.0% in
      Thai population. The frequencies of +114 GG, GT and TT genotypes were 20.8%,
      55.8% and 23.3% respectively in Chinese Han, but 50.5%, 39.0% and 10.5%
      respectively in Thai population. The genotype frequencies of -330 and +114 were
      significantly different between Chinese Han and Thai population (P < 0.05). The
      genotype frequencies of -330 in Chinese Han were significantly different from
      those in Thai, Japanese and Spain ethnic groups (P > 0.05). The polymorphisms of
      + 114 in Chinese Han were significantly different from those in Thai and Spain (P
      < 0.05), but were similar with that in Japanese (P > 0.05). CONCLUSION: IL-2 gene
      polymorphism in some different populations is significantly different. These
      differences may be one of the genetic factors contributing to the different
      pathogenesis, progress and prognosis in some diseases happening among ethnics or
      regions.

PMID- 18095605
TI  - [Single nucleotide polymorphism of XRCC1 gene in Bouyei and Shui populations].
AB  - OBJECTIVE: To analyze the single nucleotide polymorphisms (SNPs), the genotype
      combinations and the allele frequency distributions of the X-ray repair cross
      complementing gene 1 (XRCC1) C26304T, G27466A and G28152A in Bouyei and Shui
      populations. METHODS: Genomic DNA of leukocytes in venous blood was obtained from
      192 Bouyei people and 197 Shui people. The SNPs of XRCC1 C26304T, G27466A and
      G28152A were genotyped by polymerase chain reaction restrained fragment length
      polymorphism technique (PCR-RFLP). RESULTS: Three SNPs were identified in XRCC1
      C26304T, G27466A and G28152A, which were located in the exon 6, 9 and 10
      respectively. All of the gene distributions matched the equilibrium law of Hardy
      Weinberg. Eight genotype combinations were found in C26304T and G28152A. Seven
      genotype combinations were found in C26304T and G27466A. Seven genotype
      combinations were found in G28152A and G27466A. CONCLUSION: This study reveals
      the features of the SNPs, the genotype combinations and the allele frequency
      distributions of XRCC1 and provides essential data for future studies regarding
      the relationship between XRCC1 SNPs, its physiological function and diseases.

PMID- 18095606
TI  - [Identifying group G beta-hemolytic Streptococci strains by 16S rDNA sequencing].
AB  - OBJECTIVE: To identify the DNA sequences of 26 beta-hemolytic group G
      streptococci strains isolated from the swabs of patients in a glomerulonephritis
      outbreak event. METHODS: API20 Strep system and 16S rDNA sequencing were
      performed on all of the 26 isolated strains respectively. The dendrogram based on
      the analysis of the 16S rDNA sequences of four groups of G streptococci strains
      was constructed by the neighbor-joining method and boot-strap test. RESULTS: The
      API20 Strep system failed to identify the strains with less than 62% of success
      rates. All of the 26 group G beta-hemolytic streptococci isolates were identified
      as Streptococcus anginosus by the 16S rDNA sequencing, with more than 97% of
      success rates. The dendrogram illustrated that the four groups of G streptococci
      strains were clustered at the same branch with Streptococcus anginosus.
      CONCLUSION: The 16S rDNA sequencing has unique advantages over the phenotypic
      methods. It can provide detailed information of nucleotides and identify species
      of beta-hemolytic G group streptococci.

PMID- 18095607
TI  - [Antibiotic resistance and plasmid profiles of Escherichia coli in healthy human
      bodies].
AB  - OBJECTIVE: To test the antibiotic resistance of 150 Escherichia coli strains
      isolated from the faeces of healthy people in Shenzhen city. METHODS: Escherichia
      coli were isolated and identified through a procedure described in the
      Microbiology in Preventive Medicine and Inspection Technique. The antimicrobial
      susceptibility of 150 isolates to 16 antibiotics was determined by the Kirby
      Bauer method based on the Performance Standards for Anti-microbial Susceptibility
      Testing recommended by NCCLS. The plasmid profiles of the resistance strains were
      analyzed and classified. RESULTS: Over 35% of the tested strains showed
      resistance to 6 antibiotics, including Teracycline (63.33%), Nalidixic Acid
      (49.33%), Sulfamethoxazole (40.67%), Amplocilin (38.67%), Sulfamethoxazole
      timethoprim (35.33%), and Streptomycin (35.33%). All isolates were susceptible to
      Cefmelazon and Amikacin. More than 81% isolates resisted to at least one
      antibiotic, while 58. 67% and 29. 33% of the isolates resisted to more than 2 and
      5 antibiotics respectively. Two strains showed resistance to 10 antibiotics.
      CONCLUSION: Antibiotic resistance of Escherichia coli strains isolated from
      healthy people in Shenzhen city is common and serious. The number and size of
      plasmids in the isolates do not directly contribute to the antibiotic resistance.

PMID- 18095608
TI  - [Analyses of antibiotic susceptibility and plasmid profile of normal human
      intestinal Lactobacillus].
AB  - OBJECTIVE: To investigate the level of antibiotic resistance in normal human
      intestinal lactobacillus, the existence frequency of plasmid in bacterial
      strains, and the relationship between the plasmid carried by the strains and the
      antibiotic resistance profile. METHODS: The minimum inhibitory concentration
      (MIC) was determined by microbroth dilution technique. The plasmid profile of all
      strains was examined and the stability of plasmids were investigated. RESULTS:
      The antibiotic resistances of the intestinal lactobacillus strains were strong
      for ciprofldocacin, levofloxacin and vancomycin, among which it was the strongest
      for vancomycin. Most bacterial strains were tolerant to levofloxacin, gentamycin,
      tetracycline and ciprofloxacin, but susceptible to low concentration of
      rifampicin, penicillin and ampicillin. The multiple drug resistance (MDR) was
      existing in all the tested strains, and getting more severe with the increase of
      bacterial host age. 93% of lactobacillus strains contained plasmids. After
      cultured for many times, 4 bacterial strains lost some of plasmids and also, at
      the same time, lost the drug resistance to gentamycin and cephalosporin. This
      result was consistent with the that of plasmids eliminated. CONCLUSION: The
      antibiotic resistance and MDR of the lactobacillus strains in are very severe and
      correlated with people's age. Most of bacterial strains contain plasmids. There
      may be a correlation between 5.8 kb plasmid and the resistance of strains to
      gentamycin and cephalosporin.

PMID- 18095609
TI  - [Biocompatibility of bladder extracellular matrix as tissue engineering
      scaffold].
AB  - OBJECTIVE: To investve To investigate the biocompatibility of rabbit bladder
      extracellular matrix (BECM) and evaluate the feasibility of using BECM as
      scaffold for reconstruction of tissue engineering urinary tract. METHODS: By the
      application of associating the solution diosmosis, enzymatic digestion with
      chemical detergent, the rabbit bladder was decellularized to prepare the BECM, on
      which rabbit bladder transitional epithelial cells were cultured and seeded in
      vitro, of which the adhesion and proliferation were observed. MTT method was used
      to evaluate the cytotoxicity of BECM, which was implanted into the rabbit back
      for evaluating its histocompatibility meant that the toxicity, degradation and
      local inflammatory response were studied through gross observation and HE
      staining. RESULTS: The prepared rabbit BECMs were freeze-drying, and looked like
      thin semitransparent membrane. By electron microscope examination, there were no
      residues of cells found on BECM membrane, of which one side had the reticular
      fibrous structure, and the other side had the compact structure. The co-culture
      of BECM membrane with bladder transitional epithelial cells indicated that BECM
      had a good cytocompatibility. The cytotoxicity score tested by MTT method was
      number 0 and 1. The rabbits in the implant test had no abnormal response. The
      BECMs degraded gradually in vivo, and growth of peripheral tissue could be seen
      in the materials after eight weeks. CONCLUSION: The BECMs prepared by our process
      are cell-free under scanning electron microscopy. Meanwhile, the reticular
      structure of the tissue matrix is well preserved. The BECMs have the good
      cytocompatibility with transitional epithelial cells but without cytotoxicity.
      The BECMs can degrade gradually in vivo with good histocompatibility. BECM is a
      good bio-derived material of tissue engineering as scaffold for urinary tract
      reconstruction.

PMID- 18095610
TI  - [Kinetics study on intestinal absorption of bergenin in rats].
AB  - OBJECTIVE: To study the kinetics of intestine absorption of bergenin in rats.
      METHODS: The intestine absorption of bergenin in the rats was determined by in
      situ perfusion. The HPLC were used to determine the concentration of bergenin in
      the perfusate and the plasma. The concentrations of bergenin in various sites of
      the intestine and the pH values were studied. RESULTS: In the range of 0. 07-0.
      21 mg/mL, the absorption of bergenin exhibited linear kinetics. The absorption
      varied in the duodenum, jejunum, ileum and colon. In the range of pH 5.40-7.80,
      with the increasing of pH value, the Ka of bergenin decreased. CONCLUSION:
      Bergenin is absorbed by the entire intestine, but with limited amount. The
      absorption of the drug is a first-order process with the passive diffusion
      mechanism.

PMID- 18095611
TI  - [Preliminarily experimental study on biological properties of 153Sm-citrate-nano
      Hydroxyapatite].
AB  - OBJECTIVE: To investigate the biological character of new agent 153Sm-citrate
      nano-Hydroxyapatite (nano-HA) in vitro and in vivo, and to explore a new
      radiopharmaceutical for the target therapy of bone metastasis cancer. METHODS:
      The nano-HA was synthesized by collosol-gelatum method, and evaluated by
      transmission electron microscopy (TEM) and X-ray diffraction (XRD). 153Sm was
      produced at a high specific activity and excellent radionuclidic purity, with
      which nano-HA was labeled by citrate transfer ligands in the best environment. By
      adopting the independent variable method, we also studied the optimally labeled
      condition and stability of 153Sm-citrate-nano-HA in vitro. And 153Sm-citrate-nano
      HA was injected into normal rabbits for radio scanning performed. The cancer cell
      SMMC-7721 and MCF-7 cell lines were divided into two groups, and treated with
      nano-HA, 153Sm-citrate and 153Sm-citrate-nano-HA in vitro respectively, of which
      the cell survival rate was measured by MTT methods. RESULTS: Through the
      detections of TEM, XRD showed that nano-HA consisted of needle-like
      microcrystals. The label rate of 153Sm-citrate-nano-HA was more than 95%, and
      extremely stable in vitro. The radio scanning of normal rabbits showed the
      skeletal system to be clear, and other systems, for example liver, spleen and
      kidney, could also be seen. The cell culture experiments in vitro indicated that
      153Sm-citrate-nano-HA strongly inhibited the proliferation of SMMC-7721 and MCF-7
      cells. 153Sm-citrate-nano-HA's half effective inhibition concentrations were 1.89
      mg/L and 0.094 mg/L respectively; nano-HA's half effective inhibition
      concentrations were 3. 31 mg/L and 0.52 mg/L respectively; 153Sm-citrate's half
      effective inhibition concentrations were 4. 32 mg/L and 0. 67 mg/L respectively.
      CONCLUSIONS: Sm-citrate-nano-HA shows fine biological properties, and is well
      worth for further researched and prepared as a promising potential
      radiopharmaceutical in nuclidic treatment for cancer bone metastases.

PMID- 18095612
TI  - [A multicenter randomized controlled clinical trial on blood glucose lowering
      effects of domestic Acarbose (capsule) in type 2 diabetic patients].
AB  - OBJECTIVE: To assess the efficacy, tolerability, and safety of the domestic
      Acarbose capsule (DAC, produced by Luzhou Baoguang Pharmaceutical Co. LTD) in
      treating patients with type 2 diabetes mellitus. METHODS: One hundred and seventy
      nine type 2 diabetic patients were randomly divided into DAC (group A, 89
      patients) and Glucoby (group B, 90 patients) treatment groups. The trial
      consisted of a 2-4 weeks equilibrated period followed by an 8 week course of
      treatments. All of the patients were followed up at the 4th week and 8th week
      after the commencement of the treatments. One hundred and sixty five patients
      completed the trial, with 81 in group A and 84 in group B. RESULTS: At the 4th
      week of the treatments, an average reduction of 1.81 and 2.08 mmol/L of fasting
      blood glucose (FBG) was found in group A and group B, respectively (P > 0.05);
      and an average reduction of 5.43 and 5.09 mmol/ L of postprandial blood glucose
      (PBG) was found in group A and group B, respectively (P > 0.05). At the 8th week,
      an average reduction of 2.35 and 2.62 mmol/L FBG was found in group A and group
      B, respectively (P > 0.05); and an average of reduction of 5.93 and 5.98 mmol/L
      of PBG was found in group A and group B, respectively (P > 0.05); The mean
      HbA(1c) was lowered by 1.07% and 1.20% by DAC and Glucoby respectively (P >
      0.05). The incidence rate of side effects in group A was 32.53%, less than that
      in group B (48.81%). Flatulence was the most common side effect. The clinical
      effects of both Glucoby and DAC were more significant at the 8th week than at the
      4th week. CONCLUSION: DAC is as effective and safe as Glucobay for treating type
      2 diabetic patients.

PMID- 18095613
TI  - [Detecting methamphetamine and amphetamine with high performance liquid
      chromatography].
AB  - OBJECTIVE: To establish a method for detecting methamphetamine (MA) and
      amphetamine (AMP) with high performance liquid chromatography (HPLC). METHODS:
      Both MA and AMP were isolated on a C18 column and methanol-phosphate buffer
      (0.015 mol/L NaH2PO4) at a flow rate of 1.0 mL/min. The 190-360 nm ultraviolet
      spectrum was examined, with 215 nm as the detection wavelength. RESULTS: The MA
      and AMP were well isolated and determined. The MA determined by the HPLC had good
      linearity with the real value at the range from 1.4 to 270 microg/mL (R2=1), with
      an average recovery rate of 102.5%. The detectable Limit was 0.73 microg/mL (S/N
      > or =3). The AMP determined by the HPLC had a good linearity with the real value
      at the range from 0.9 to 580 microg/mL (R2 = 0.9999), with an average recovery
      rate of 101.7%. The detectable limit was 0.52 microg/mL (S/N > or =3). Both intra
      day and inter-day precisions expressed by relative standard deviations of the MA
      and AMP were less than 2.4%. CONCLUSION: This is a simple, rapid and accurate
      method for detecting methamphetamine and amphetamine.

PMID- 18095614
TI  - [Construction of an in vitro carotid artery bifurcation model].
AB  - OBJECTIVE: To construct a solid carotid artery bifurcation model with general
      applicability that simulates the real shape. METHODS: The diameter of the carotid
      artery was measured using ultrasonic cardiograph. A modified carotid artery model
      was constructed according to the tuning fork model geometry with the geometry
      size being rectified. The flow fields in the carotid artery model were detected
      by the particle imaging velocimetry technique. RESULTS: The characteristics of
      the distribution of the flow fields in the carotid artery model were similar to
      those in the human bodies. CONCLUSION: The carotid artery we constructed well
      resembles the real shape and has good representativeness and practicability,
      which provides a reliable experimental platform for further research.

PMID- 18095615
TI  - [Nano ultra high performance liquid chromatography coupled with time-of-flight
      mass spectrometer for detecting low molecular weight polypeptides in zebrafish
      embryos].
AB  - OBJECTIVE: To apply the nano-ultra high performance liquid chromatography
      coupling with time-of-flight mass spectrometer (nano-UPLC-TOF-MS) to detect the
      low molecular weight polypeptides in zebrafish embryos. METHODS: Zebrafish
      embryos were collected 24 hours after fertilization and the outer chorion was
      removed. And then the yolk was removed with mechanical forces, of which the
      efficiency was validated by microscope and SDS-PAGE; the low molecular weight
      polypeptide was extracted with corresponding solution, and followed by separation
      and detection with nano-UPLC-TOF-MS. RESULTS: Mechanical vortex almost completely
      removed yolk cells of zebrafish embryos, from which the special solution
      extracted effectively low molecular weight polypeptides for the later detection.
      As demonstrated by nano-UPLC-TOF-MS, the polypeptide peak showed between 22 and
      24. 5 min, and the m/z ration of most of polypeptides were between 800-1400.
      CONCLUSION: Nano-OPLC-TOF-MS is effective to detect low molecular weight
      polypeptides, and low molecular weight peptides definitely exist in zebrafish
      embryos, of which the relative molecular mass seems to be 800 to 1400, probably
      consists of about 10 residues.

PMID- 18095616
TI  - [Detecting perfluorooctanoic acid by reversed phase high performance liquid
      chromatography with pre-column ultraviolet derivatization].
AB  - OBJECTIVES: To establish a reversed phase high performance liquid chromatographic
      method with pre-column ultraviolet derivatization for the determination of
      perfluorooctanoic acids (PFOA) in sewage and urine. METHODS: PFOA in sewage and
      urine formed an ion-pair with tetrabutylammonium (TBA) and were extracted into
      MTBE. The PFOA then reacted with omega-bromoacetophenone (omega-BAP) in
      acetonitrile and produced materials quantifiable by HPLC with UV detector.
      RESULTS: The detection limit of the proposed method was 7.0 microg/L with a
      relative standard deviation of less than 10%. The recoveries for real samples
      ranged from 85.3% to 116%. CONCLUSION: The proposed method is suitable for the
      determination of PFOA in sewage and urine.

PMID- 18095617
TI  - [Simultaneous determination of monosaccharides and oligosaccharides in Lycium
      barbarum L. by high performance liquid chromatography].
AB  - OBJECTIVE: To develop a rapid approach of refractive index detection with high
      performance liquid chromatography (HPLC) for the determination of rhamnose,
      fructose, glucose, surose and maltose in Lycium barbarum L. METHODS: The sample
      was extracted with water and the analyte was separated by Zorbax Carbohydrate
      column with acetonitrile-water as mobile phase. RESULTS: Good linear correlations
      between the concentrations and the peak areas of the analyte were found, with the
      correlation coefficients ranging from 0.9976 to 0.9998. The spiked recovery rates
      ranged from 92.27% to 101.93%, with 1.85%-3.27% of relative standard deviations
      (n=5). The limits of detection (S/N =3) were 4-6 mg/kg. CONCLUSION: The proposed
      method is suitable for the determination of monosaccharide and oligosaccharide in
      Lycium barbarum L.

PMID- 18095619
TI  - [Embryonic stem cells and human chimeras].

PMID- 18095618
TI  - [Simultaneous pancreas-kidney transplantation (SPK) for an old age male with type
      2 diabetes complicated with end-stage renal disease (ESRD): a case report].
AB  - We reported the first case of simultaneous pancreas-kidney transplantation (SPK)
      in our hospital. The recipient is a 65 year old male, who suffered type 2
      diabetes for 15 years and renal dysfunction for 5 years and other diabetic
      complications such as retinopathy, peripheral neuropathy. SPK was performed
      successfully for him in March, 2007, in which the donor kidney was put in left
      iliac fossa, while the donor pancreas grafted to set in right iliac fossa of
      recipient, with pancreas exocrine drainage controlled by anastomosis to the small
      bowel and endocrine release done to the circulatory system. Serum C-peptide,
      Creatinine and Blood urea nitrogen became normal levels at day 1, 4 and 11 of
      post-operation respectively. The concentration of blood glucose was stabilized
      gradually to normal level and therefore the injected insulin was stopped using to
      the patient at day 16 of post-operative days. OGTT test showed the function of
      grafted pancreas was normal 3 weeks after transplant, and no transplantation
      related complications occurred. With the recipient followed up for 6 months, both
      his blood glucose level and renal function maintained normal without using
      injected insulin, and he was getting to recover from other diabetic complications
      also.

PMID- 18095620
TI  - [Saddle nose deformity].

PMID- 18095621
TI  - [Positron emission tomography in oncology: an update].
AB  - Positron emission tomography (PET) has been widely used for several years for
      staging and response evaluation in oncology. It is time to critically review its
      role in routine patient care. [18F]-labelled fluorodeoxyglucose ([18F]-FDG)
      remains the radiotracer of choice in most indications. Its high sensitivity, the
      half-life of 110 minutes and the easy production of this radiotracer explain its
      routine use although the specificity is not very good. Infectious or inflammatory
      processes can mimic tumours. Appropriate selection of patients studied in the
      recommended indications and interpretation of images by an experienced team
      having access to both clinical information and other diagnostic studies allows
      reducing the risk of false positives. Although PET is highly accurate, not all
      patients suffering from cancer need a PET study. Major improvements were also
      observed with conventional imaging techniques over the past 10 years. It is
      important to avoid long waiting lists because otherwise treatment delay may
      counterbalance the benefit of PET studies.

PMID- 18095622
TI  - [Acute respiratory tract infections in children. Lower infections].

PMID- 18095624
TI  - [Community-acquired pneumonia in children].
AB  - Empiric antibiotic therapy in emergency remains frequent in community-acquired
      pneumonia in children primarily because of the high number of different causes.
      Streptococcus pneumoniae results in severe pneumonia and represents between 15 to
      30% of etiologies. Lack of specificity of diagnostic procedures is important.
      Lobar consolidation is radiologically seen in less than half of cases and
      laboratory data, except for high procalcitonin level, are poorly reliable.
      Pneumonia due to Mycoplasma pneumoniae are frequent after age of 2 years,
      reaching 40 to 60% of causes in ambulatory teenagers. They must be given
      macrolides without important delay because sequellae are possible. The exact
      number of viral pneumonia is difficult to establish because of lack of reliable
      diagnostic methods. Bacterial superinfections are probably overestimated during
      acute phase but viral infections may lead to bacterial pneumonia 2 to 4 weeks
      after the initial episode. In absence of specific clinical or laboratory data,
      empiric antibiotic treatment must include pneumococci and their penicillin
      resistant strains. Amoxicillin is the antibiotic of choice with a higher efficacy
      on resistant pneumococci than oral cephalosporins. In case of clinical failure of
      amoxicillin, mycoplasma infection is highly probable and patient must receive
      macrolides. Epidemiology is progressively changing with anti-pneumococcal
      immunisation but difficulties in diagnosis and in choice of empiric antibiotic
      treatment will remain important. Future studies in immunised children are needed
      to check the importance of pneumococcal infections due to serotypes not included
      in the vaccines

PMID- 18095623
TI  - [Techniques used for the diagnostic of upper and lower respiratory tract viral
      infections].
AB  - Techniques used for the diagnostic of upper and lower respiratory tract viral
      infections Techniques used for the diagnostic of upper and lower respiratory
      tract viral infections include conventional procedures and the new molecular
      tools. Serology has no interest for diagnosis. Antigen detection can be carried
      out by simple, easy and cheap tools. They are available at hospital and in
      community practice as well for the detection of influenza virus, RSV, hMPV,
      parainfluenza virus and adenovirus. To look for viruses which are non detectable
      by antigen detection assays (rhinovirus, coronavirus, bocavirus, polyomavirus...)
      or in severe or complicated respiratory lower infections, the use of molecular
      tools is highly indicated.

PMID- 18095625
TI  - [Influenza in children].
AB  - It has been recently demonstrated that influenza is not predominantly an adult
      disease but affects massively the children and spreads to the community from
      them. Affected children may be admitted to hospital and the maximal risk concerns
      those younger than 1 year and mainly <6 months of age. For them, the risk to be
      admitted is equivalent to that observed in elderly and adults with underlying
      conditions. Asthma and chronic diseases enhance the risk in children in the same
      proportions as observed in adults. Influenza may lead to death, infants aged 0-6
      months being the most affected. Young children with influenza exhibit a non
      specific respiratory illness and often non respiratory manifestations (isolated
      fever, GI tract illness, convulsions). Influenza rapid "doctor tests" are now
      available and may be used at the physician's surgery. Treating fever is the most
      important purpose. Aspirin use should be avoided due to an increased risk of Reye
      syndrome. Antibiotic prescription is not indicated, except in case of bacterial
      super infection. Neuraminidase inhibitors may be used for treatment of influenza
      in children from 1 year (oseltamivir) or 5 years (zanamivir). These medications
      may also be used for prophylaxis of the disease.

PMID- 18095626
TI  - [Acute bronchiolitis in infants].
AB  - Clinical criteria used to define acute broncholitis in infants are not worldwide
      consensual diagnostic criteria. Respiratory failures as well as young age account
      for the severity of the disease. Laboratory analyses are useless in community
      medical practice. Infectious complications are due to secondary infection with
      usual respiratory pathogenic bacteria. In France the treatment mainly consists in
      physical therapy whose efficiency is currently being evaluated by randomized
      studies. Prevention of the disease relies on hygiene measures and in an
      integrated physician-physiotherapist collaboration.

PMID- 18095627
TI  - [A new virus: the human metapneumovirus].

PMID- 18095628
TI  - [What to expect from vaccine prevention in acute respiratory tract infection in
      children?].
AB  - Acute respiratory tract infections are the main cause of morbidity and mortality
      in infants and young children. They are the first cause of hospitalisation in
      industrialised countries. A safe and efficient antiVRS vaccine would be a very
      important advance but, unfortunately, it does not exist at this moment.
      Recommendations of the influenza vaccine could be extended, as it is the case in
      USA, to decrease infants hospitalisations who are under one year of age and to
      decrease acute respiratory tract infections in children and adults. Theses
      vaccines are susceptible to play a role in coinfections and bacterial super
      infections. Haemophilus influenzae conjugate vaccine is very efficient against
      pneumonia due to this bacteria. Heptavalent pneumococcal conjugate vaccine
      decreases the number of otitis media and particularly recidivant and complicated
      otitis media. This vaccine decreases the number of pneumonia and hospitalizations
      for pneumonia in U.S.A. This vaccine acts on the carriage of pneumococcal strains
      and plays a role in decreasing antibiotic resistance. Epidemiological
      surveillance of pneumococcal strains is necessary because of a possible selection
      of strains due to the vaccine.

PMID- 18095629
TI  - [Sequelae of viral lower respiratory tract infections in children].
AB  - Viral lower respiratory tract infections in children can lead to long-term
      complications. Of these, the most studied one is the triggering effect of viral
      infection on the subsequent development of asthma. A better understanding of the
      interactions between host genetic factors and virus-specific factors is necessary
      to determine whether severe viral lower respiratory tract infections can really
      induce asthma or if it is the predisposition to asthma which induces an increased
      risk of severe infection in the case of viral infection. Bronchiolitis
      obliterans, less common though very severe, is another complication. Adenovirus
      is the leading cause of this complication, leading to persistent and severe
      obstructive airway diseases. No treatment exists to prevent this adverse
      progression efficiently enough during the course of severe viral infections.

PMID- 18095630
TI  - [Acute lower respiratory tract infections of children in MEDLINE].

PMID- 18095631
TI  - [What is bronchiolitis?].

PMID- 18095632
TI  - [Continuing medical education: effectiveness in 2007].

PMID- 18095633
TI  - [National ranking exam. N54. What could happen at the exam?].

PMID- 18095634
TI  - [Cataract].

PMID- 18095635
TI  - [Behavior disorders in adolescents].

PMID- 18095636
TI  - [Appendicitis in the child and the adult].

PMID- 18095637
TI  - [Acute renal failure. Anuria].

PMID- 18095638
TI  - [Pediatric grand rounds].

PMID- 18095639
TI  - DNA methylation-dependent regulation of BORIS/CTCFL expression in ovarian cancer.
AB  - Brother of the Regulator of Imprinted Sites (BORIS/CTCFL) is an autosomal cancer
      germline (CG) or cancer-testis antigen gene and paralog of CTCF that has been
      proposed to function as an oncogene in human cancer via dysregulation of the
      cancer epigenome. Here we show that genetic disruption of DNA methylation in
      human cancer cells induces BORIS expression, coincident with DNA hypomethylation
      and an altered histone H3 modification pattern at the BORIS promoter. Rapid
      amplification of cDNA ends (RACE) mapping revealed that the transcriptional start
      site of BORIS in human testis, DNMT deficient human cancer cells, and human
      epithelial ovarian cancer (EOC) tissues, is similar and lies within the 5' CpG
      island. The BORIS promoter is repressed by CpG methylation in a dose-dependent
      fashion, indicating a direct role for DNA methylation in BORIS transcriptional
      regulation. In human ovarian cancer cell lines, 5-aza-2'-deoxycytidine treatment
      activates BORIS expression and reduces BORIS promoter DNA methylation. We
      quantitatively measured BORIS mRNA expression and promoter DNA methylation in
      normal ovary (NO; n = 10) and epithelial ovarian cancer (EOC; n = 77) and found
      that, compared to NO, EOC tumors show increased BORIS expression and decreased
      BORIS methylation. Importantly, BORIS promoter DNA methylation shows a
      significant inverse correlation with BORIS mRNA expression in EOC (Kendall's Tau
      = -0.235, P = 0.007, n = 63). These data establish promoter DNA hypomethylation
      as a mechanism leading to BORIS expression in human ovarian cancer.

PMID- 18095640
TI  - A novel class of intrinsic proteasome inhibitory gene transfer peptides.
AB  - Proteasomes are multisubunit enzymes responsible for the degradation of many
      cytosolic proteins. The inhibition of the proteasome has been the subject of
      intense interest in the development of drug therapies. We have previously
      demonstrated that simultaneous administration of a tripeptide aldehyde proteasome
      inhibitor (MG115 or MG132) with a peptide (Cys-Trp-Lys18) DNA condensate boosted
      gene expression by 30-fold in cell culture. In the present study, we have
      developed a convergent synthesis to allow the incorporation of a proteasome
      inhibitor tripeptide into the C-terminal end of a gene delivery peptide. The
      resulting peptides formed DNA condensates that mediated a 100-fold enhancement in
      gene expression over a control peptide lacking all or part of the tripeptide
      inhibitor. Gene transfer peptides possessing intrinsic proteasome inhibitors were
      also found to be nontoxic to cells in culture. These results suggest that
      intrinsic proteasome inhibition may also be used to boost the efficiency of
      peptide-mediated nonviral gene delivery systems in vivo.

PMID- 18095641
TI  - Biochemical and structural evaluation of highly selective 2-arylbenzoxazole-based
      transthyretin amyloidogenesis inhibitors.
AB  - To develop potent transthyretin (TTR) amyloidogenesis inhibitors that also
      display high binding selectivity in blood, it proves useful to systematically
      optimize each of the three substructural elements that comprise a typical
      inhibitor: the two aryl rings and the linker joining them. In the first study,
      described herein, structural modifications to one aryl ring were evaluated by
      screening a library of 2-arylbenzoxazoles bearing thyroid hormone-like aryl
      substituents on the 2-aryl ring. Several potent and highly selective
      amyloidogenesis inhibitors were identified that exhibit minimal thyroid hormone
      nuclear receptor and COX-1 binding. High resolution crystal structures (1.3-1.5
      A) of three inhibitors (2f, 4f, and 4d) in complex with TTR were obtained to
      characterize their binding orientation. Collectively, the results demonstrate
      that thyroid hormone-like substitution patterns on one aryl ring lead to potent
      and highly selective TTR amyloidogenesis inhibitors that lack undesirable thyroid
      hormone receptor or COX-1 binding.

PMID- 18095642
TI  - Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro
      1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor
      agonist for the treatment of obesity.
AB  - The synthesis and SAR of a novel 3-benzazepine series of 5-HT2C agonists is
      described. Compound 7d (lorcaserin, APD356) was identified as one of the more
      potent and selective compounds in vitro (pEC50 values in functional assays
      measuring [(3)H]phosphoinositol turnover: 5-HT2C = 8.1; 5-HT2A = 6.8; 5-HT2B =
      6.1) and was potent in an acute in vivo rat food intake model upon oral
      administration (ED50 at 6 h = 18 mg/kg). Lorcaserin was further characterized in
      a single-dose pharmacokinetic study in rat (t1/2 = 3.7 h; F = 86%) and a 28-day
      model of weight gain in growing Sprague-Dawley rat (8.5% decrease in weight gain
      observed at 36 mg/kg b.i.d.). Lorcaserin was selected for further evaluation in
      clinical trials for the treatment of obesity.

PMID- 18095643
TI  - 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one-based HIV-1 integrase inhibitors.
AB  - The bis-salicylhydrazides class of HIV-1 integrase (IN) inhibitors has been
      postulated to function by metal chelation. However, members of this series
      exhibit potent inhibition only when Mn2+ is used as cofactor. The current study
      found that bis-aroylhydrazides could acquire inhibitory potency in Mg2+ using
      dihydroxybenzoyl substituents as both the right and left components of the
      hydrazide moiety. Employing a 2,3-dihydro-6,7-dihydroxy-1 H-isoindol-1-one ring
      system as a conformationally constrained 2,3-dihydroxybenzoyl equivalent provided
      good selectivity for IN-catalyzed strand transfer versus the 3'-processing
      reactions as well as antiviral efficacy in cells using HIV-1 based vectors.

PMID- 18095644
TI  - Profiling the Monascus pilosus proteome during nitrogen limitation.
AB  - Monascus species have the unique ability to economically produce many secondary
      metabolites. However, the influence of nitrogen limitation on Monascus secondary
      metabolite production and metabolic performance remains unclear. Varying the
      carbon/nitrogen (C/N) ratios in the range from 20 to 60 in cultivation of
      Monascus pilosus by glucose nitrate medium, our resulting data showed that red
      pigment production was significantly suppressed and more sensitive to nitrogen
      limitation than cellular biomass growth at a C/N ratio of 60. Using a comparative
      proteomic approach, combining two-dimensional gel electrophoresis, matrix
      assisted laser desorption ionization time-of-flight/time-of-flight liquid
      chromatography-mass spectrometry, and tandem mass spectrometry, proteins with
      modified expression in the nitrogen-limited (C/N ratio 60) Monascus filamentous
      cells were identified. The results revealed that the deregulated proteins
      identified were involved in amino acid biosynthesis, protein translation,
      antioxidant-related enzymes, glycolysis, and transcriptional regulation. The
      results suggested that, under nitrogen limitation-induced suppression of protein
      translation and of expression of the related energy-generating enzymes, nitrogen
      limitation induced a switch of metabolic flux from glycolysis to the
      tricarboxylic acid (TCA) cycle for maintaining cellular energy homeostasis,
      resulting in repression of the metabolic shift of the polyketide biosynthesis
      pathway for red pigment production.

PMID- 18095645
TI  - The role of iron in peroxidation of polyunsaturated fatty acids in liposomes.
AB  - This work investigated iron-catalyzed lipid oxidation in marine phospholipid
      liposomes. Oxygen consumption was used as a method to study lipid oxidation at pH
      5.5 and 30 degrees C. The relationship between consumed oxygen and amount of
      peroxides (PV) and thiobarbituric reactive substances (TBARS) formed showed that
      both Fe2+ and Fe3+ catalyzed lipid oxidation. When Fe2+ was added to liposomes at
      a concentration of approximately 10 microM, an initial drop in dissolved oxygen
      (oxygen uptake rate >258 microM/min), followed by a slower linear oxygen uptake
      (oxygen uptake rate 4-6 microM/min), was observed. Addition of Fe3+ induced only
      the linear oxygen uptake. The initial fast drop in dissolved oxygen was due to
      oxidation of Fe2+ to Fe3+ by preexisting lipid peroxides (rate 79 microM
      Fe2+/min). Fe3+ is reduced by peroxides to Fe2+ at a slow rate (0.25 microM
      Fe3+/min at 30 degrees C) in a pseudo-first-order reaction. The redox cycling
      between Fe2+ and Fe3+ leads to an equilibrium between Fe2+ and Fe3+ resulting in
      a linear oxygen uptake. During the linear oxygen uptake, the interaction of Fe
      (3+) with lipid peroxide is the rate-limiting factor. Both alkoxy and peroxy
      radicals are formed by breakdown of peroxides by Fe2+ and Fe3+. These radicals
      react with fatty acids giving lipid radicals reacting with oxygen.

PMID- 18095646
TI  - Assessing lipid coating of the human oral cavity after ingestion of fatty foods.
AB  - The coating on the oral surface plays a significant role in mouthfeel perception,
      which is an important attribute governing perception of reduced-fat or low-fat
      food products. The aim of this work was to develop efficient methods to quantify
      the coating of the lipids covering the oral surface after ingestion of fatty
      foods. Three different approaches were assessed to investigate the in-mouth
      behavior of fluid foods in a subject. A first approach determined the mass of
      lipids retained in the oral cavity by rinsing it out. A second approach evaluated
      the thickness of the lipid coating on the tongue by fluorescence measurement
      using a dye incorporated in oil. Finally, a third approach measured local lipid
      thickness by adsorption of the lipids on a filter paper. All applied methods
      showed results in the same range. The thickness of the lipid coating was on
      average between 5 and 32 microm. The total lipid recoveries obtained by
      controlled rinses from the oral cavity were approximately 96 and 50% for single
      filter paper. A fast, simple, and quantitative method was developed to measure
      the thickness of the lipid coating on an oral surface after ingestion of fatty
      foods. This work presents the potential of the method to investigate in-mouth
      distribution and residues of lipids and establishes new avenues to study in-mouth
      behavior of food components and its influence on the sensory perception.

PMID- 18095647
TI  - Content, composition, and bioactivity of the essential oils of three basil
      genotypes as a function of harvesting.
AB  - A study was conducted to evaluate the effect of cut on biomass productivity, oil
      content, composition, and bioactivity of Ocimum basilicum L. (cvs. German and
      Mesten) and Ocimum sanctum L. (syn. O. tenuiflorum L.) (cv. Local) in
      Mississippi. Yields of basil herbage and essential oil were high and comparable
      to those reported in the literature. Essential oil content of O. basilicum cv.
      German varied from 0.40 to 0.75%, the oil content of cv. Mesten varied from 0.50
      to 0.72%, and the oil content of cv. Local (of O. sanctum) ranged from 0.17 to
      0.50% in air-dried basil. Herbage and essential oil yields of cvs. German and
      Mesten of O. basilicum increased with the second and then again with the third
      cut, whereas herbage and oil yields of cv. Local of O. sanctum increased with the
      third cut relative to the previous cuts. Overall, essential oil yields were 115,
      123, and 51 kg/ha for the cvs. German, Mesten, and Local, respectively. The major
      oil constituents of cvs. German and Mesten (of O. basilicum) were (-)-linalool
      (30-40%) and eugenol (8-30%), whereas the major oil constituents of cv. Local (of
      O. sanctum) were eugenol (8-43%) and methylchavicol (15-27%). Essential oils from
      both species grown in Mississippi showed in vitro activity against Leishmania
      donovani (IC50 = 37.3-49.6 microg/mL), which was comparable to the activity of
      commercial oil (IC50 = 40-50 microg/mL). Minor basil oil constituents (+)-delta
      cadinene, 3-carene, alpha-humulene, citral, and (-)- trans-caryophyllene had
      antileishmanial activity, whereas other constituents were ineffective. None of
      the oil was cytotoxic to mammalian cells.

PMID- 18095648
TI  - Effect of gelatinization and hydrolysis conditions on the selectivity of starch
      hydrolysis with alpha-amylase from Bacillus licheniformis.
AB  - Enzymatic hydrolysis of starch can be used to obtain various valuable
      hydrolyzates with different compositions. The effects of starch pretreatment,
      enzyme addition point, and hydrolysis conditions on the hydrolyzate composition
      and reaction rate during wheat starch hydrolysis with alpha-amylase from Bacillus
      licheniformis were compared. Suspensions of native starch or starch gelatinized
      at different conditions either with or without enzyme were hydrolyzed. During
      hydrolysis, the oligosaccharide concentration, the dextrose equivalent, and the
      enzyme activity were determined. We found that the hydrolyzate composition was
      affected by the type of starch pretreatment and the enzyme addition point but
      that it was just minimally affected by the pressure applied during hydrolysis, as
      long as gelatinization was complete. The differences between hydrolysis of
      thermally gelatinized, high-pressure gelatinized, and native starch were
      explained by considering the granule structure and the specific surface area of
      the granules. These results show that the hydrolyzate composition can be
      influenced by choosing different process sequences and conditions.

PMID- 18095649
TI  - Mass spectrometry based sensor strategies for the authentication of oysters
      according to geographical origin.
AB  - This study was undertaken to investigate the relevance of using the pyrolysis-MS
      (Py-MS) technique to discriminate the production area of oysters harvested over
      two years and to assess from the data of the second year of harvest the potential
      of an alternative MS-based technique, the solid phase microextraction-MS (SPME
      MS), to perform this discrimination. Oysters were harvested in various areas of
      France, and models of discrimination according to harvest season were built from
      Py-MS fingerprints and from virtual SPME-MS fingerprints obtained by summing the
      mass spectra generated by the SPME-GC-MS system. The treatment of the Py-MS data
      by a 21-12-3 artificial neural networks led to a correct classification of only
      89.2% of the oyster samples according to shoreline. The misclassifications thus
      did not allow use of the Py-MS technique as a relevant tool for authentication of
      oyster origin. The assessment of the potential of the virtual SPME-MS
      fingerprints to discriminate the production area of oysters was undertaken on a
      part of the sample set. The virtual SPME-MS data were pretreated according to two
      methods, filtering of raw data (FRD) and comprehensive combinatory standard
      correction (CCSC), a recently developed chemometric method used for the
      correction of instrumental signal drifts in MS systems. The results obtained with
      the virtual SPME-MS fingerprints are promising because this technique, when the
      data were pretreated by the CCSC method, led to a successful discrimination of
      the oyster samples not only according to shoreline but also according to
      production region. This study confirms that an efficient correction method (CCSC)
      of instrumental drifts can considerably increase the discriminative information
      contained in the volatile fraction of food products.

PMID- 18095650
TI  - Enzymatic synthesis and identification of two trisaccharides produced from
      lactulose by transgalactosylation.
AB  - The enzymatic transgalactosylation during lactulose hydrolysis was studied using
      the beta-galactosidase from Kluyveromyces lactis and an initial lactulose
      concentration of 250 g/L. During hydrolysis of lactulose, the formation of two
      novel trisaccharides was followed by high-performance anion-exchange
      chromatography with pulsed amperometric detection (HPAEC-PAD). A maximum
      trisaccharide yield of 14.05% was observed at 91.9% of lactulose hydrolysis. The
      two novel trisaccharides obtained by transglycosylation of lactulose were
      isolated and fully characterized by an extensive nuclear magnetic resonance (NMR)
      study. Complete structure elucidation and full proton and carbon assignment were
      carried out using 1D ( 1H, 13C, and 1D TOCSY) and 2D (gCOSY, TOCSY, ROESY, gHSQC,
      and gHMBC) NMR experiments. The trisaccharides were shown to be lactulose-based
      structures; the main one has a Gal unit linked to C-6 of the galactose moiety,
      and the other one has a Gal unit linked to C-1 of the fructose moiety.
      Transglycosylation of lactulose allows for the obtention of galacto
      oligosaccharides with new glycosidic structures and would open new routes to the
      synthesis of prebiotics.

PMID- 18095651
TI  - pH-triggered reversible "stealth" polycationic micelles.
AB  - Amphiphilic polycations with a "stealth" cationic nature have been designed and
      synthesized by the PEGylation of polycationic amphiphile via a novel pH
      responsible benzoic imine linker. The linkage is stable in aqueous solution at
      physiological pH but cleaves in slight acidic conditions such as the
      extracellular environment of solid tumor and endosomes. The polymeric micelle
      formed from the amphiphilic "stealth" polycation contains a pH-switchable
      cationic surface driven by the reversible detachment/reattachment of the
      shielding PEG chains due to the cleavage/formation process of the imine linkage.
      At physiological pH, the micellar surface was shielded by the PEG corona, leading
      to lower cytotoxicity and less hemolysis, whereas in a mild acidic condition like
      in endosomes or solid tumors, the deshielding of the PEG chains exposed the
      positive charge on the micellar surface and retained the membrane disrupting
      ability. The amphiphilic "stealth" polycation is potentially useful as a drug
      targeting system toward tumors via endocytosis and trafficked through the
      endosomal pathway.

PMID- 18095652
TI  - Effect of cell density on osteoblastic differentiation and matrix degradation of
      biomimetic dense collagen scaffolds.
AB  - Plastic compression of hyperhydrated collagen gels produces tissue-like scaffolds
      of enhanced biomechanical properties. By increasing collagen density, these
      scaffolds could be developed into highly Biomimetic cell-seeded templates. When
      utilizing three-dimensional (3-D) scaffold systems for tissue repair, and indeed
      when investigating the cytocompatibility of two-dimensional (2-D) surfaces, the
      cell seeding density is often overlooked. In this study, we investigated this
      potentially critical parameter using MG-63 cells seeded in the dense collagen
      scaffolds. This is conducted within the overall scope of developing these
      scaffolds for bone repair. Cell proliferation, osteoblastic differentiation, and
      matrix remodelling capacity in relation to various seeding densities, ranging
      from 10(5) to 10(8) cells/ml compressed collagen, were evaluated in vitro. This
      was performed using the AlamarBlue assay, quantitative polymerase chain reaction
      (qPCR), and tensile mechanical analysis respectively. Variations in cell seeding
      density significantly influenced cell proliferation where lower initial seeding
      density resulted in higher proliferation rates as a function of time in culture.
      Gene transcription levels for alkaline phosphatase (ALPL), runt-related
      transcription factor 2 (RUNX2), and osteonectin (SPARC) were also found to be
      dependent on the cell density. While ALPL transcription was down-regulated with
      culturing time for all seeding densities, there was an increase in RUNX2 and
      SPARC transcription, particularly for scaffolds with cell densities in the range
      10(6)-10(7) cells/ml collagen. Furthermore, this range of seeding density
      affected cell capacity in conducting collagenous matrix degradation as
      established by analyzing matrix metalloproteinase 1 (MMP1) transcription and
      scaffold mechanical properties. This study has shown that the seeded cell
      population in the three-dimensional dense collagen scaffolds clearly affected the
      degree of osteoblastic cell proliferation, differentiation, and some aspects of
      matrix remodelling activity. The seeding density played a major role in
      influencing the corresponding cell differentiation and cell-matrix interaction.

PMID- 18095653
TI  - Cytotoxic triterpenoid saponins acylated with monoterpenic acid from
      Pithecellobium lucidum.
AB  - Three new oleanane-type triterpene saponins, named pithelucosides A-C (1-3),
      together with two known saponins (4, 5) were isolated from the roots of
      Pithecellobium lucidum. The structures of the new saponins were established on
      the basis of extensive 1D and 2D NMR experiments and mass spectrometry and
      confirmed by acid and alkaline hydrolysis. Compounds 1-5 and 7 (pro-sapogenin
      obtained from the mild alkaline hydrolysate of 1) were evaluated for cytotoxic
      activity on five human tumoral cell lines (HCT-8, Bel-7402, BGC-823, A549, and
      A2780) and for hemolytic property against rabbit erythrocytes. Compounds 2-5
      showed significant cytotoxic activities with IC50 values of 0.61-7.56 microM. All
      tested compounds did not exhibit any hemolytic activity in the concentration
      range 0.01-100 microM.

PMID- 18095654
TI  - Noreupenifeldin, a tropolone from an unidentified ascomycete.
AB  - Noreupenifeldin ( 2), a new monotropolone derivative of the bistropolone
      eupenifeldin ( 1), was isolated from an unidentified ascomycete by bioassay
      guided fractionation as part of our search for new anthelmintics. The structure
      of 1 was confirmed by comparison with literature data. The structure of 2 was
      elucidated from MS and 1D and 2D NMR data. Compounds 1 and 2 are diastereomers of
      pycnidione ( 3) and epolone A ( 4), respectively. Compounds 1- 3 were evaluated
      for their anthelmintic activity against the parasitic worm Hemonchus contortus.
      Compounds 1 and 3 exhibited modest in vitro activity, showing EC 90 50 and 83
      microg/mL, respectively, in reducing motility of L3 larvae of H. contortus.
      Compound 2 was inactive, indicating that the second tropolone moiety is required
      for activity.

PMID- 18095655
TI  - Construction and validation of an automated flow hydrogenation instrument for
      application in high-throughput organic chemistry.
AB  - This manuscript details the construction of a fully automated flow hydrogenation
      apparatus for use in high-throughput organic synthesis. The instrument comprises
      of a Bohdan robot platform coupled with a ThalesNano H-cube hydrogenator and a
      series of solvent valves and pumping mechanisms. Using this instrument, we have
      been able to fully automate a number of key transformations that could not
      otherwise be conveniently undertaken in a high-throughput manner.

PMID- 18095656
TI  - Metabolic activation of a novel 3-substituted indole-containing TNF-alpha
      inhibitor: dehydrogenation and inactivation of CYP3A4.
AB  - SPD-304 is a recently discovered small-molecule TNF-alpha antagonist. However,
      SPD-304 contains a potentially toxic 3-alkylindole moiety. Previous studies on 3
      methylindole and the 3-alkylindole-containing drugs zafirlukast and MK-0524
      structural analogues found that they were bioactivated by cytochrome P450s
      through a dehydrogenation process to form 3-methyleneindolenine intermediates
      that are electrophilic alpha,beta-unsaturated iminium species. These
      electrophiles could react with protein and/or DNA nucleophilic residues to cause
      toxicities. In the present study, we found that SPD-304 was bioactivated through
      a similar dehydrogenation mechanism to produce a similar electrophilic 3
      methyleneindolenine intermediate. The electrophile was trapped with nucleophilic
      glutathione and identified by LC/MS/MS. The iminium or another reactive
      intermediate also was a mechanism-based inactivator of CYP3A4. The inactivation
      parameters were K I = 29 microM and k inact = 0.047 min (-1). In addition, SPD
      304 was metabolized through hydroxylation, N-dealkylation, and epoxidation
      pathways, and several metabolites and glutathione adducts were characterized by
      tandem mass spectrometry. The metabolism profile was also evaluated by in silico
      molecular docking of SPD-304 into the active site of CYP3A4, which predicted that
      the dehydrogenation reaction was initiated by 3-methylene C-H atom abstraction at
      the trifluoromethylphenyl-1 H-indol-3-ylmethyl portion of SPD-304. Hydroxylation
      of the 6'-methyl of the dimethylchromone portion of SPD-304 was the other major
      predicted metabolic pathway. The molecular models correlated precisely with
      experimental metabolic results. In summary, dehydrogenation of SPD-304 may cause
      toxicities through the formation of electrophilic intermediates and cause drug
      drug interactions through CYP3A4 inactivation.

PMID- 18095657
TI  - 1H NMR-based metabolomic analysis of liver, serum, and brain following ethanol
      administration in rats.
AB  - Ethanol is a widely used drug that is consumed in large amounts for pharmacologic
      effects. Elimination of ethanol alters metabolism in the liver and throughout an
      organism. Ethanol's effect on metabolites can influence the regulation of key
      pathways such as gluconeogenesis. We adopted a proton NMR-based metabolomic
      approach to study ethanol-induced metabolic changes in liver, blood, and brain
      tissue from rats exposed to either a single dose of ethanol or a chronic 4 day
      binge-ethanol protocol. Both acute and binge ethanol caused (i) decreased
      glucose, lactate, and alanine in liver and serum; (ii) increased acetate in liver
      and serum; and (iii) increased acetoacetate in serum. Binge-ethanol increased
      liver beta-hydroxybutyrate and decreased betaine. Pretreatment with the
      antioxidant butylated hydroxytoluene (BHT) increased betaine and reduced ethyl
      glucuronide (EtG) in livers of binge-ethanol animals, as compared to those not
      pretreated with BHT. We found no change in brain metabolites after a single dose
      of ethanol. Unsupervised principal component (PC) analysis of spectral data from
      liver and serum successfully discriminated treatment groups, based largely on the
      biochemical differences outlined above, confirming the results of manual
      analysis. To explain the observed lack of gluconeogenesis following ethanol
      treatment and to resolve apparently discordant results from previous studies, we
      propose a model in which decreased hepatic alanine removes inhibition on pyruvate
      kinase, thus permitting a futile cycle that diverts phosphoenolpyruvate away from
      gluconeogenesis. This is a new mechanism that biochemically elucidates the well
      known, yet unexplained, "empty calorie" phenomenon of ethanol. Reduction of EtG
      by pretreatment with BHT suggests that BHT and perhaps other compounds may alter
      the pharmacokinetics of EtG so that EtG may not always be a sensitive marker for
      ethanol abuse.

PMID- 18095658
TI  - Zn2+ enhances the molecular chaperone function and stability of alpha-crystallin.
AB  - Alpha-crystallin, the major eye lens protein, is a molecular chaperone that plays
      a crucial role in the suppression of protein aggregation and thus in the long
      term maintenance of lens transparency. Zinc is a micronutrient of the eye, but
      its molecular interaction with alpha-crystallin has not been studied in detail.
      In this paper, we present results of in vitro experiments that show bivalent zinc
      specifically interacts with alpha-crystallin with a dissociation constant in the
      submillimolar range (Kd approximately 0.2-0.4 mM). We compared the effect of Zn2+
      with those of Ca2+, Cu2+, Mg2+, Cd2+, Pb2+, Ni2+, Fe2+, and Co2+ at 1 mM on the
      structure and chaperoning ability of alpha-crystallin. An insulin aggregation
      assay showed that among the bivalent metal ions, only 1 mM Zn2+ improved the
      chaperone function of alpha-crystallin by 30% compared to that in the absence of
      bivalent metal ions. Addition of 1 mM Zn2+ increased the yield of alpha
      crystallin-assisted refolding of urea-treated LDH to its native state from 33 to
      38%, but other bivalent ions had little effect. The surface hydrophobicity of
      alpha-crystallin was increased by 50% due to the binding of Zn2+. In the presence
      of 1 mM Zn2+, the stability of alpha-crystallin was enhanced by 36 kJ/mol, and it
      became more resistant to tryptic cleavage. The implications of enhanced stability
      and molecular chaperone activity of alpha-crystallin in the presence of Zn2+ are
      discussed in terms of its role in the long-term maintenance of lens transparency
      and cataract formation.

PMID- 18095659
TI  - The flavodoxin from Helicobacter pylori: structural determinants of
      thermostability and FMN cofactor binding.
AB  - Flavodoxin has been recently recognized as an essential protein for a number of
      pathogenic bacteria including Helicobacter pylori, where it has been proposed to
      constitute a target for antibacterial drug development. One way we are exploring
      to screen for novel inhibitory compounds is to perform thermal upshift assays,
      for which a detailed knowledge of protein thermostability and cofactor binding
      properties is of great help. However, very little is known on the stability and
      ligand binding properties of H. pylori flavodoxin, and its peculiar FMN binding
      site together with the variety of behaviors observed within the flavodoxin family
      preclude extrapolations. We have thus performed a detailed experimental and
      computational analysis of the thermostability and cofactor binding energetics of
      H. pylori flavodoxin, and we have found that the thermal unfolding equilibrium is
      more complex that any other previously described for flavodoxins as it involves
      the accumulation of two distinct equilibrium intermediates. Fortunately the
      entire stability and binding data can be satisfactorily fitted to a model,
      summarized in a simple phase diagram, where the cofactor only binds to the native
      state. On the other hand, we show how variability of thermal unfolding behavior
      within the flavodoxin family can be predicted using structure-energetics
      relationships implemented in the COREX algorithm. The different distribution and
      ranges of local stabilities of the Anabaena and H. pylori apoflavodoxins explain
      the essential experimental differences observed: much lower Tm1, greater
      resistance to global unfolding, and more pronounced cold denaturation in H.
      pylori. Finally, a new strategy is proposed to identify using COREX structural
      characteristics of equilibrium intermediate states populated during protein
      unfolding.

PMID- 18095660
TI  - Novel transcriptional activities of vitamin E: inhibition of cholesterol
      biosynthesis.
AB  - Vitamin E is a dietary lipid that is essential for vertebrate health and
      fertility. The biological activity of vitamin E is thought to reflect its ability
      to quench oxygen- and carbon-based free radicals and thus to protect the organism
      from oxidative damage. However, recent reports suggest that vitamin E may also
      display other biological activities. Here, to examine possible mechanisms that
      may underlie such nonclassical activities of vitamin E, we investigated the
      possibility that it functions as a specific modulator of gene expression. We show
      that treatment of cultured hepatocytes with (RRR)-alpha-tocopherol alters the
      expression of multiple genes and that these effects are distinct from those
      elicited by another antioxidant. Genes modulated by vitamin E include those that
      encode key enzymes in the cholesterol biosynthetic pathway. Correspondingly,
      vitamin E caused a pronounced inhibition of de novo cholesterol biosynthesis. The
      transcriptional activities of vitamin E were mediated by attenuating the post
      translational processing of the transcription factor SREBP-2 that, in turn, led
      to a decreased transcriptional activity of sterol-responsive elements in the
      promoters of target genes. These observations indicate that vitamin E possesses
      novel transcriptional activities that affect fundamental biological processes.
      Cross talk between tocopherol levels and cholesterol status may be an important
      facet of the biological activities of vitamin E.

PMID- 18095661
TI  - Ultrafast ring-closure reaction of photochromic indolylfulgimides studied with UV
      pump-IR-probe spectroscopy.
AB  - The ring-opening and ring-closure reactions of a photochromic indolylfulgimide
      are investigated with femtosecond vibrational spectroscopy. Spectral signatures
      due to excited-state decay and vibrational cooling are seen in the mid-IR region.
      For the ring-opening reaction triggered with visible pulses, a lifetime of the
      excited electronic state of 4 ps was obtained in polar solution. In a nonpolar
      solvent, this time constant is reduced to 2 ps. The ring-closure reaction induced
      with UV pulses displays an excited-state lifetime and thus a building of the
      photoproduct of roughly 0.5 ps. For all processes, the subsequent cooling occurs
      on a 15-ps time scale lasting up to approximately 50 ps. The time-resolved IR
      measurements do not support the existence of any long-living intermediate states.

PMID- 18095662
TI  - Synthesis, characterization, and ab initio theoretical study of a molecularly
      imprinted polymer selective for biosensor materials.
AB  - Despite the complex phenomena involved in encoding template molecule information
      within stable synthetic polymers to yield selective and efficient molecular
      recognition processes, molecularly imprinted polymers (MIP) are increasingly
      finding broad areas of application. Molecular interactions, both during the
      polymerization of the functional monomers in the presence of the template and
      during the processes of specific recognition after template removal, are key
      determinants of an effective MIP. Covalent and noncovalent template imprinting
      have been employed to achieve specific recognition sites. In the present study, a
      molecularly imprinted biocompatible polymer, having a high capacity and affinity
      for the dye template, nickel(II) phthalocyanine tetrasulfonic acid, has been
      prepared. UV-visible spectroscopy, FTIR spectroscopy, and ICP analysis were used
      to investigate the aspects of the synthesis, binding capacity, and adsorption
      kinetics of the system. Poly(allylamine) cross-linked with epichlorohydrin has
      been used to represent an amino-functional receptor. Binding isotherms and
      capacities were correlated with the degree of template removal. Kinetic studies
      of binding allowed diffusion mechanisms to be evaluated for the fine particulate
      MIP. Ab initio molecular orbital calculations were performed using Hartree-Fock,
      MP2, and density functional theory methods to determine the most likely
      mechanisms of molecular imprinting. Suitable theoretical models have been
      constructed to mimic the interactions between the template molecule and the
      polymer. Simulation of the vibrational spectra was also undertaken to make
      meaningful assignments to experimentally determined spectral bands resulting from
      these template MIP receptor interactions.

PMID- 18095663
TI  - General methodology to optimize damping functions to account for charge
      penetration effects in electrostatic calculations using multicentered multipolar
      expansions.
AB  - We developed a methodology to optimize exponential damping functions to account
      for charge penetration effects when computing molecular electrostatic properties
      using the multicentered multipolar expansion method (MME). This methodology is
      based in the optimization of a damping parameter set using a two-step fast local
      fitting procedure and the ab initio (Hartree-Fock/6-31G** and 6-31G**+)
      electrostatic potential calculated in a set of concentric grid of points as
      reference. The principal aspect of the methodology is a first local fitting step
      which generates a focused initial guess to improve the performance of a simplex
      method avoiding the use of multiple runs and the choice of initial guesses. Three
      different strategies for the determination of optimized damping parameters were
      tested in the following studies: (1) investigation of the error in the
      calculation of the electrostatic interaction energy for five hydrogen-bonded
      dimers at standard and nonstandard hydrogen-bonded geometries and at
      nonequilibrium geometries; (2) calculation of the electrostatic molecular
      properties (potential and electric field) for eight small molecular systems
      (methanol, ammonia, water, formamide, dichloromethane, acetone, dimethyl
      sulfoxide, and acetonitrile) and for the 20 amino acids. Our results show that
      the methodology performs well not only for small molecules but also for
      relatively larger molecular systems. The analysis of the distinct parameter sets
      associated with different optimization strategies show that (i) a specific
      parameter set is more suitable and more general for electrostatic interaction
      energy calculations, with an average absolute error of 0.46 kcal/mol at hydrogen
      bond geometries; (ii) a second parameter set is more suitable for electrostatic
      potential and electric field calculations at and outside the van der Waals (vdW)
      envelope, with an average error decrease >72% at the vdW surface. A more general
      amino acid damping parameter set was constructed from the original damping
      parameters derived for the small fragments and for the amino acids. This damping
      set is more insensitive to protein backbone and residue side-chain conformational
      changes and can be very useful for future docking and molecular dynamics protein
      simulations using ab initio based polarizable classical methods.

PMID- 18095664
TI  - A theoretical study of the photochemical isomerization reactions of furans from
      the triplet state.
AB  - The mechanisms of photoisomerization reactions were investigated theoretically
      using a model system of 2-methylfuran with the CASSCF (10-electron/8-orbital
      active space) and MP2-CAS methods and the 6-311(d,p) basis set. After 2
      methylfuran molecules are produced in the T(1) state by photoexcitation at 254
      nm, intersystem crossing to the S(0) surface is the most probable pathway for
      deactivation. Relaxing to the S(0) state, the 2-methylfuran molecules can
      dissociate into 3-methylcyclopropene and carbon monoxide products. Otherwise,
      they may revert to singlet 2-methylfuran or undergo photorearrangement to produce
      3-methylfuran. These stepwise mechanisms are consistent with the available
      experimental observations.

PMID- 18095665
TI  - Joint statistical analysis of multichannel time series from single quantum dot
      (Cy5)n constructs.
AB  - One of the major challenges in single-molecule studies is how to extract reliable
      information from the inevitably noisy data. Here, we demonstrate the unique
      capabilities of multichannel joint statistical analysis of multispectral time
      series using Foster resonance energy transfer (FRET) in single quantum dot (QD)
      organic dye hybrids as a model system. The multispectral photon-by-photon
      registration allows model-free determination of intensity change points of the
      donor and acceptor channels independently. The subsequent joint analysis of these
      change points gives high-confidence assignments of acceptor photobleaching events
      despite the interference from background noise and from intermittent blinking of
      the QD donors and acceptors themselves. Finally, the excited-state lifetimes of
      donors and acceptors are calculated using the joint maximum likelihood estimation
      (MLE) method on the donor and acceptor decay profiles, guided by a four-state
      kinetics model.

PMID- 18095666
TI  - Structure of polydisperse inverse ferrofluids: theory and computer simulation.
AB  - By using theoretical analysis and molecular dynamics simulations, we investigate
      the structure of colloidal crystals formed by nonmagnetic microparticles (or
      magnetic holes) suspended in ferrofluids (called inverse ferrofluids), by taking
      into account the effect of polydispersity in size of the nonmagnetic
      microparticles. Such polydispersity often exists in real situations. We obtain an
      analytical expression for the interaction energy of monodisperse, bidisperse, and
      polydisperse inverse ferrofluids. Body-centered tetragonal (bct) lattices are
      shown to possess the lowest energy when compared with other sorts of lattices and
      thus serve as the ground state of the systems. Also, the effect of microparticle
      size distributions (namely, polydispersity in size) plays an important role in
      the formation of various kinds of structural configurations. Thus, it seems
      possible to fabricate colloidal crystals by choosing appropriate polydispersity
      in size.

PMID- 18095667
TI  - Solution structures of cyclosporin a and its complex with dysprosium(III) in SDS
      micelles: NMR and molecular dynamics studies.
AB  - Cyclosporin A (CsA) is a cyclic naturally occurring peptide used to prevent graft
      rejection in organ transplantations. Its immunosuppressive activity is due to the
      formation of a complex with cyclophilin A (Cyp), in which the cis 9MeLeu-10MeLeu
      amide bond of CsA assumes a trans conformation. The mechanism of the
      conformational inversion has not been delineated, but it has been postulated that
      metal ions binding induces a conformational change that enables CsA to bind Cyp.
      In this work, we solved the structures of CsA in sodium dodecyl sulfate (SDS)
      micelles (which enhance its solubility and mimic the hydrophobic environment
      clinically used for drug delivery) and its complex with Dy(III) ion, whose
      coordination chemistry is frequently used to reproduce the effect of Ca(II). The
      paramagnetic properties of Dy(III) allowed us to build up a structure using
      proton relaxation enhancements, which remains stable in a MD simulation in the
      micelle environment.

PMID- 18095668
TI  - Diffusionless crystal growth from glass has precursor in equilibrium liquid.
AB  - A remarkable property of certain glass-forming liquids is that a fast mode of
      crystal growth is suddenly activated near the glass transition temperature, Tg,
      and continues in the glassy state. This mode of growth, termed GC (glass
      crystal), is so fast that it is not limited by molecular diffusion in the bulk
      liquid. We have studied the GC growth by growing multiple crystal polymorphs from
      the liquid of ROY, currently the top system for the number of coexisting
      polymorphs of known structures. We observed a new feature of GC growth that
      conflicts with its current description in the literature. We found that the GC
      mode is not truly a new growth mode suddenly appearing near Tg but one already
      existing in the equilibrium liquid up to approximately 1.15 Tg, in the form of
      fast-growing fibers. This finding is relevant to testing different explanations
      for GC growth and favors the view that GC growth is enabled by molecular motions
      that are native to the glass but still persist in the viscous liquid.

PMID- 18095669
TI  - Cooperative Iron(II) spin crossover complexes with N4O2 coordination sphere.
AB  - Two new spin crossover complexes [FeL(py)(2)] (1) and [FeL(DMAP)(2)] (2) with L
      being a tetradentate N(2)O(2)(2-) coordinating Schiff-base-like ligand [([3,3']
      [1,2-phenylenebis(iminomethylidyne)]bis(2,4-pentanedionato)(2-)-N,N',O(2),O(2)'],
      py = pyridine and DMAP = p-dimethylaminopyridine have been investigated using
      temperature-dependent susceptibility and thermogravimetric and photomagnetic
      measurements as well as Mossbauer spectroscopy and X-ray structure analysis. Both
      complexes show a cooperative spin transition with an approximately 9 K wide
      thermal hysteresis loop in the case of 2 (T(1/2) upward arrow = 183 K and T(1/2)
      downward arrow = 174 K) and an approximately 2 K wide thermal hysteresis loop in
      the case of the pyridine diadduct 1 (T(1/2) upward arrow = 191 K and T(1/2)
      downward arrow = 189 K). The spin transition was additionally followed by
      different temperature-scanning calorimetry and Mossbauer spectroscopy for 2, and
      a good agreement for the transition temperatures obtained with the different
      methods was found. Results from X-ray structure analysis indicate that the
      cooperative interactions are due to elastic interactions in both compounds. They
      are more pronounced in the case of 2 with very short intermolecular iron-iron
      distances of 7.2 A and several intense C-C contacts. The change of the spin state
      at the iron center is accompanied by a change of the O-Fe-O angle, the so-called
      bit of the equatorial ligand, from 108 degrees in the high-spin state to 90
      degrees in the low-spin state. The reflectivity measurements of both compounds
      give at low temperature indication that at the sample surface the light-induced
      excited spin state trapping (LIESST) effect occurs. In bulk condition using a
      SQUID magnetometer the complex 2 displays some photomagnetic properties with an
      photoexcitation level of 60% and a T(LIESST) value of 53 K.

PMID- 18095670
TI  - Detailed spectroscopic, thermodynamic, and kinetic characterization of nickel(II)
      complexes with 2,2'-bipyridine and 1,10-phenanthroline attained via equilibrium
      restricted factor analysis.
AB  - The molar absorptivity curves of the mono and bis nickel(II) complexes of 2,2'
      bipyridine and 1,10-phenanthroline have been deduced from the composite
      absorbance data of a series of equilibrium solutions in methanol using
      equilibrium-restricted factor analysis, a technique for extracting spectral and
      thermodynamic information for component species involved in solution equilibria.
      The solutions achieve equilibrium slowly (t(1/2) approximately 100 min) as the
      amounts of the tris and methanolato complexes are initially in excess. The
      relative formation constants at 293 K have been determined with a high degree of
      accuracy, especially for the bipyridine complexes: log(K(1)/K(2)) = 0.340(4) and
      log(K(2)/K(3)) = 1.091(6). Solubility limitations compromised the accuracy of the
      thermodynamic results for the phenanthroline complexes.

PMID- 18095671
TI  - Origin of compressed Jahn-Teller octahedra in sterically strained manganese(III)
      complexes.
AB  - A method is presented that enables the bond length changes resulting from the
      Jahn-Teller interaction to be predicted from a knowledge of the angular geometry
      of the complex and the identity of the ligators. The calculation of the energy
      minimum within the subspace of the Jahn-Teller active e skeletal mode proceeds by
      diagonalization of the potential energy component of the cubic Ee Jahn-Teller
      problem, incorporating low-symmetry distortions by way of angular overlap model
      calculations. The theory is applied to a series of manganese(III) complexes
      formed with tetradentate tripodal ligands that largely dictate the angular
      coordinates. A good account of the contrasting molecular structures is obtained
      by allowing the sigma-bonding strength to vary according to expectations based
      upon the spectrochemical series.

PMID- 18095672
TI  - Synthesis and thermal chemistry of copper (I) guanidinates.
AB  - Copper (I) guanidinate dimers were generated by a salt metathesis route and
      structurally characterized. The guanidinates differed from the known amidinate
      dimers because of a large torsion of the dimer ring. This had a direct effect on
      their thermal chemistry. The thermal reactivity was investigated by several
      methods, including a novel temperature-resolved, gas-phase method that was
      monitored by mass spectrometry. The copper guanidinates underwent carbodiimide
      deinsertion to produce copper metal at temperatures between 225 -and 250 degrees
      C in the gas phase and at 125 degrees C in solution. The amidinate investigated
      also showed copper deposition at 190 degrees C in the gas phase, and 135 degrees
      C in solution, but without carbodiimide deinsertion. The guanidinate compounds
      deposited crystalline copper at 225 degrees C in a simple chemical vapor
      deposition experiment.

PMID- 18095673
TI  - Study of negative thermal expansion and shift in phase transition temperature in
      Ti4+- and Sn4+-substituted ZrW2O8 materials.
AB  - The negative-thermal-expansion material ZrW(2)O(8) is known to undergo an order
      disorder phase transition which affects its expansion behavior. In this study,
      Ti(4+) and Sn(4+) are examined as possible substituting ions for the Zr(4+)
      position in ZrW(2)O(8). This substitution leads to a decrease in cell parameters,
      as the ionic radii of the substituents are smaller than the Zr(4+) ionic radius.
      A remarkable decrease in transition temperature is noticed. DSC is used to
      quantify the enthalpy and entropy changes during the phase transition in order to
      reveal the mechanisms behind this decrease. It is shown that the strength of the
      M-O bond plays an important role, as it is a partner in the rigid unit mode
      motion and the order-disorder transition mechanism.

PMID- 18095674
TI  - Spectroscopic and theoretical study of a mononuclear manganese(III) complex
      exhibiting a tetragonally compressed geometry.
AB  - Inelastic neutron scattering and high-field electron paramagnetic resonance data
      are presented for [Mn(bpia)(OAc)(OCH(3))](PF(6)), where bpia is bis(picolyl)(N
      methylimidazole-2-yl)amine. Modeling of the data to the conventional fourth-order
      spin-Hamiltonian yielded the following parameters: D = 3.526(3) cm(-1), E =
      0.588(6) cm(-1), B(0)(4) = -0.00084(7) cm(-1), B(2)( 4)= -0.002(2) cm(-1), (4)(4)
      = -0.0082(5) cm(-1), g(x) = 1.98(1), g(y) = 1.952(6), and g(z) = 1.978(5). The
      complex is of particular interest given the biochemical activity and the unusual
      stereochemistry distinguished by a rare example of a tetragonally compressed
      octahedron and a pronounced angular distortion imposed by the tetradentate
      tripodal bpia ligand. Ligand field, density functional theory, and complete
      active space self-consistent field ab initio calculations are presented that aim
      to relate the spectroscopic data to the molecular geometry.

PMID- 18095675
TI  - Synthesis, structures, and magnetic properties of metal-coordination polymers
      with benzenepentacarboxylate linkers.
AB  - Three hybrid organic-inorganic coordination polymers with benzenepentacarboxylate
      (BPCA) linkers, [Co3(C6H(COO)5)(OH)(H2O)3] (1-Co), [Zn3(C6H(COO)5)(OH)(H2O)3] (2
      Zn), and [Co5(C6H(COO)5)2(H2O)12].(H2O)12 (3-Co), were synthesized hydrothermally
      and were characterized structurally and magnetically. 1-Co and 2-Zn are
      isostructural [C2/c; Z=8; 1-Co, a=19.5350(6) A, b=10.4494(4) A, and c=13.2353(5)
      A, beta=97.2768(8) degrees; 2-Zn, a=19.5418(9) A, b=10.3220(10) A, and
      c=13.4660(10) A, beta=98.455(10) degrees] with three-dimensional structures that
      contain [M6] secondary building units bridged by BPCA ligands. A different cobalt
      based compound, 3-Co, forms at lower pH and lower reaction temperature. Its
      structure [P21/c; Z=2; a=12.6162(2) A, b=11.3768(2) A, and c=15.3401(3) A,
      beta=91.539(1) degrees] is a more loosely packed framework with free
      (noncoordinated) carboxylic groups pointing at water-filled cavities in the
      framework. The magnetic phase diagram of 1-Co established through detailed
      magnetic measurements shows a metamagnetic transition below TN=3.8 K. The less
      packed compound 3-Co, on the other hand, remains paramagnetic above 1.9 K. The
      three compounds are the first examples of coordination polymers with
      benzenepentacarboxylate linkers and fill the gap of coordination polymers
      involving benzenepolycarboxylate linkers of the general type C6H6-n(COOH)n, where
      n=2-6.

PMID- 18095676
TI  - Synthesis of ordered ultrathin ZnO nanowire bundles on an indium-tin oxide
      substrate.
AB  - Ultrathin ZnO nanowire bundles have been synthesized on an indium-tin oxide
      substrate without any catalyst by using a simple thermal evaporation method,
      where self-organized ZnO nanowire bundles were grown on the hexagonal heads of
      ZnO nanocolumns. The nanowires obtained typically have diameters of 8 nm, with
      lengths extending to 0.25 microm. The size is the same order of magnitude as the
      ZnO exciton Bohr radius (aB). Room-temperature photoluminescence measurement
      shows a prominent peak at 374 nm (3.32 eV), which is about 100 meV blue-shifted
      from the bulk ZnO emission.

PMID- 18095677
TI  - 31P magic angle spinning NMR spectroscopy of paramagnetic rare-earth-substituted
      Keggin and Wells-Dawson solids.
AB  - Paramagnetic rare-earth elements have been examined as NMR structural probes in
      polyoxoanionic solids, which have a variety of applications as luminescent
      materials that are usually disordered and therefore intractable by traditional
      structural methods. Thirteen Keggin and Wells-Dawson polyoxotungstates containing
      substitutions with lanthanides of different effective magnetic moments have been
      examined by 31P magic angle spinning NMR spectroscopy. The electron-nuclear
      dipolar interaction dominating the spinning sideband envelopes is determined by
      the lanthanide's magnetic moment and was found to be a sensitive probe of the
      nature of the polyoxoanion, of the positional isomerism, and of the ion
      stoichiometry. Electron-nuclear dipolar anisotropies computed based on the point
      dipole approximation are generally in good agreement with the experimental
      results. The choice of a specific lanthanide as a structural probe can be
      tailored to the desired distance range between the phosphorus atoms and the
      paramagnetic centers to be probed. This approach is expected to be particularly
      useful in the paramagnetic polyoxoanionic materials lacking long-range order.

PMID- 18095678
TI  - Induced-fit in the gas phase: conformational effects on the enantioselectivity of
      chiral tetra-amide macrocycles.
AB  - The structure, stability, and reactivity of proton-bound diastereomeric [M x H x
      A]+ complexes between some amino acid derivatives (A) and several chiral tetra
      amide macrocycles (M) have been investigated in the gas phase by ESI-FT-ICR and
      ESI-ITMS-CID mass spectrometry. The displacement of the A guest from the
      diastereomeric [M x H x A]+ complexes by reaction with the 2-aminobutane
      enantiomers (B) exhibits a distinct enantioselectivity with regards to the
      leaving amino acid A and, to a minor extent, to the amine reactant B. The
      emerging selectivity picture, discussed in the light of molecular mechanics
      calculations, provides compelling evidence that the most stable conformers of the
      selected chiral tetra-amide macrocycles M may acquire in the gas phase a
      different conformation by induced fit on complexation with some representative
      amino acid derivatives A. This leads to the coexistence in the gas phase of
      stable diastereomeric [M x H x A]+ eq-eq and ax-ax structures, in proportions
      depending on the configuration of A and M and characterized by different
      stability and reactivity toward the 2-aminobutane enantiomers. The
      enantioselectivity of the gas-phase A-to-B displacement in the diastereomeric [M
      x H x A]+ complexes essentially reflects the free energy gap between the homo-
      and heterochiral [M x H x A]+ complexes, except when the tetra-amidic host
      presents an additional macrocycle generated by a decamethylene chain. In this
      case, the measured enantioselectivity mostly reflects the stability difference
      between the relevant diastereomeric transition structures.

PMID- 18095680
TI  - Locking of helicity and shape complementarity in diarylethene dimers on graphite.

PMID- 18095679
TI  - Reversibility effects on the stereoselectivity of Pt(II)-mediated cascade poly
      ene cyclizations.
AB  - Cyclization of 1,5-dienes bearing nucleophilic traps with electrophilic
      trisphosphine pincer ligated Pt(II) complexes results in the formation of a
      polycyclic Pt-alkyl via a Pt(eta2-alkene) intermediate. With electron-rich
      triphosphine ligands, an equilibrium between the Pt(eta2-alkene) and Pt-alkyl was
      observed. The position of the equilibrium was sensitive to ligand basicity,
      conjugate acid strength, solvent polarity, and ring size. In cases where the
      ligand was electron poor and did not promote retrocyclization, the kinetic
      products adhering to the Stork-Eschenmoser postulate were observed (E-alkenes
      give trans-ring junctions). When retrocyclization was rapid, alternative
      thermodynamic products resulting from multistep rearrangements were observed (cis
      [6,5]-bicycles). Under both kinetic and thermodynamic conditions, remote methyl
      substituents led to highly diastereoselective reactions. In the case of trienol
      substrates, long-range asymmetric induction from a C-ring substituent was
      considerably attenuated and only modest diastereoselectivity was observed
      (approximately 2:1). The data suggest that for a tricyclization, the long-range
      stereocontrol results from diastereo-selecting interactions that develop during
      the organization of the nascent rings. In contrast, the bicyclization
      diastereoselectivities result from reversible cascade cyclization.

PMID- 18095681
TI  - Complexation-induced transition of nanorod to network aggregates: alternate
      porphyrin and cyclodextrin arrays.
AB  - Tetrakis(permethyl-beta-cyclodextrin)-modified zinc(II) porphyrin (1) and
      tetra(beta-cyclodextrin)-modified zinc(II) porphyrin (2) were synthesized via
      "click chemistry". Intermolecular inclusion complexation of these structurally
      similar 1 and 2 with tetrasodium tetraphenylporphyrintetrasulfonate (3) led to
      formation of two distinctly different nanoarchitectures with alternate porphyrin
      and cyclodextrin arrays, which were proven to be network and nanorod aggregates,
      respectively, by using transmission electron microscopy, atomic force microscopy,
      and scanning electron microscopy. From the results of comparative studies in
      different solutions, we elucidated the mechanisms that result in nanorod to
      network aggregates transition, concluding that the complexation strength of
      porphyrin with cyclodextrin is a crucial factor to activate the potential binding
      sites of a molecular building block.

PMID- 18095682
TI  - Origins of selectivity for the [2+2] cycloaddition of alpha,beta-unsaturated
      ketones within a porous self-assembled organic framework.
AB  - This article studies the origins of selectivity for the [2+2] cycloadditions of
      alpha,beta-unsaturated ketones within a porous crystalline host. The host, formed
      by the self-assembly of a bis-urea macrocycle, contains accessible channels of
      approximately 6 A diameter and forms stable inclusion complexes with a variety of
      cyclic and acyclic alpha,beta-unsaturated ketone derivatives. Host 1 crystals
      provide a robust confined reaction environment for the highly selective [2+2]
      cycloaddition of 3-methyl-2-cyclopentenone, 2-cyclohexenone, and 2-methyl-2
      cyclopentenone, forming their respective exo head-to-tail dimers in high
      conversion. The products are readily extracted from the self-assembled host and
      the crystalline host can be efficiently recovered and reused. Molecular modeling
      studies indicate that the origin of the observed selectivity is due to the
      excellent match between the size and shape of these guests to dimensions of the
      host channel and to the preorganization of neighboring enones into favorable
      reaction geometries. Small substrates, such as acrylic acid and
      methylvinylketone, were bound by the host and were protected from photoreactions.
      Larger substrates, such as 4,4-dimethyl-2-cyclohexenone and mesityl oxide, do not
      undergo selective [2+2] cycloaddition reactions. In an effort to understand these
      differences in reactivity, we examined these host-guest complexes by
      thermogravimetric analysis (TGA), NMR, powder X-ray diffraction (PXRD) and
      molecular modeling.

PMID- 18095683
TI  - Liposome encapsulation of conjugated polyelectrolytes: toward a liposome beacon.

PMID- 18095684
TI  - 1-Hexene isomerization over sulfated mesoporous Ta oxide: the effects of active
      site and confinement.

PMID- 18095688
TI  - A pre-RNA candidate revisited: both enantiomers of flexible nucleoside
      triphosphates are DNA polymerase substrates.

PMID- 18095689
TI  - Toward a rational design of poly(2,7-carbazole) derivatives for solar cells.
AB  - On the basis of theoretical models and calculations, several alternating
      polymeric structures have been investigated to develop optimized poly(2,7
      carbazole) derivatives for solar cell applications. Selected low band gap
      alternating copolymers have been obtained via a Suzuki coupling reaction. A good
      correlation between DFT theoretical calculations performed on model compounds and
      the experimental HOMO, LUMO, and band gap energies of the corresponding polymers
      has been obtained. This study reveals that the alternating copolymer HOMO energy
      level is mainly fixed by the carbazole moiety, whereas the LUMO energy level is
      mainly related to the nature of the electron-withdrawing comonomer. However,
      solar cell performances are not solely driven by the energy levels of the
      materials. Clearly, the molecular weight and the overall organization of the
      polymers are other important key parameters to consider when developing new
      polymers for solar cells. Preliminary measurements have revealed hole mobilities
      of about 1 x 10(-3) cm2 x V(-1) x s(-1) and a power conversion efficiency (PCE)
      up to 3.6%. Further improvements are anticipated through a rational design of new
      symmetric low band gap poly(2,7-carbazole) derivatives.

PMID- 18095690
TI  - Enantioselective organo-SOMO catalysis: the alpha-vinylation of aldehydes.

PMID- 18095691
TI  - Identification of (8S,9S,10S)-8,10-dimethyl-1-octalin, a key intermediate in the
      biosynthesis of geosmin in bacteria.

PMID- 18095693
TI  - Synthesis and characterization of meso-aryl-substituted subchlorins.

PMID- 18095692
TI  - Geosmin biosynthesis. Mechanism of the fragmentation-rearrangement in the
      conversion of germacradienol to geosmin.

PMID- 18095694
TI  - Total syntheses of the assigned structures of lituarines B and C.

PMID- 18095695
TI  - Nanorods of endohedral metallofullerene derivative.

PMID- 18095697
TI  - Synthesis and cytotoxicity of a new class of potent decapeptide macrocycles.
AB  - Described are the syntheses of five decapeptides that are C-2-symmetrical
      derivatives of the natural product pentapeptide sansalvamide A. Derivatives were
      made using a succinct convergent synthesis. These analogues share no structural
      homology to current cancer drugs, are cytotoxic at levels on par with existing
      drugs treating cancers, and demonstrate selectivity for drug-resistant pancreatic
      cancer cell lines over noncancerous cell lines. These molecules are excellent
      chemotherapeutic leads in the search for new anticancer agents.

PMID- 18095698
TI  - Asymmetric hydrogenation of unsaturated ureas with the BIPI ligands.
AB  - Asymmetric hydrogenation of unsaturated urea esters with the BIPI Ligands has
      been examined. Optimization of the P-N ligand structure has led to the
      development of chiral rhodium catalysts capable of producing the targets with
      >99% ee. The critical phosphine borane SNAr reaction needed for ligand synthesis
      has been optimized to give the adducts in high yield at ambient temperature with
      no racemization. An extremely concise, economical, and scalable sequence to these
      important new ligands for catalysis of asymmetric hydrogenation has been
      developed.

PMID- 18095699
TI  - A convergent synthesis of the tricyclic core of the dictyosphaeric acids.
AB  - The first synthetic route to the tricyclic core of the dictyosphaeric acids has
      been established starting from readily available (S)-(-)-4-(tert
      butyldimethylsilyloxy)cyclohexenone and involving 9 steps, including a ring
      closing metathesis to produce a 13-membered macrolactone, and a doubly tethered
      intramolecular Michael addition.

PMID- 18095700
TI  - Toward an artificial aldolase.
AB  - A new functional polymer where proline is bonded to polystyrene through a 1,2,3
      triazole linker depicts characteristics targeted for an artificial aldolase. In
      spite of the hydrophobicity of the polymer backbone, the resin swells in water
      with building of an aqueous microenvironment. This property, arising from the
      formation of a hydrogen-bond network connecting the proline and 1,2,3-triazole
      fragments, is translated into a very high catalytic activity and
      enantioselectivity toward direct aldol reactions in water.

PMID- 18095701
TI  - An environmentally benign synthesis of cis-2,6-disubstituted tetrahydropyrans via
      indium-mediated tandem allylation/Prins cyclization reaction.
AB  - In the presence of indium metal, 3-iodo-2-[(trimethylsilyl)methyl]propene (1)
      reacts with sequentially added aldehydes to provide cis-2,6-disubstituted
      tetrahydropyrans in good yields. Evidence suggests that InI, formed upon aldehyde
      (R1CHO) allylation in aqueous media, acts as a promoter for the silyl-Prins
      reaction with the second equivalent of added aldehyde (R2CHO). The preparation of
      cyclohexenyl-fused pyrans via this one-pot, three-component coupling process is
      presented, as is a short formal synthesis of (+/-)-centrolobine.

PMID- 18095702
TI  - Synthesis and spectral properties of near-infrared aminophenyl-, hydroxyphenyl-,
      and phenyl-substituted heptamethine cyanines.
AB  - Diverse meso-aminophenyl-, hydroxyphenyl-, and phenyl-substituted heptamethine
      cyanine dyes were prepared by a modified Suzuki--Miyaura method in good yields.
      In addition, direct Suzuki coupling of Vilsmeier--Haack reagent extends the
      procedure to the synthesis of otherwise difficult cyanine dyes containing
      multiple heteroatoms in the indolium ring. The new compounds possess excellent
      spectral properties and can be used to label bioactive molecules and
      nanoparticles. The one-pot synthesis procedure eliminates the cumbersome steps of
      protecting/deprotecting amino or hydroxy groups.

PMID- 18095703
TI  - A multicomponent synthesis of triazinane diones.
AB  - An efficient, one-pot synthetic protocol toward triazinane diones, a rather
      unexplored class of heterocyclic scaffolds combining phosphonates, nitriles,
      aldehydes, and isocyanates is described. The optimization of the reaction,
      synthesis of a small library of different triazinane diones, as well as
      alternative routes toward the triazinane dione scaffold are discussed.

PMID- 18095704
TI  - Preparation and addition--elimination reactions of benzyl alpha,beta,beta
      trifluoroacrylate. A new stereoselective approach to (Z)-beta-substituted
      alpha,beta-difluoroacrylates.
AB  - Benzyl alpha,beta,beta-trifluoroacrylate (1) was prepared in good yield via the
      reductive Br-F elimination of benzyl 2-bromo-2,3,3,3-tetrafluoropropanoate or the
      palladium-catalyzed cross-coupling reaction of 1,2,2-trifluorovinylstannane with
      benzyl chloroformate. On treating 1 with various Grignard reagents or dialkylzinc
      reagents in the presence of copper(I) salt, the corresponding beta-substituted
      alpha,beta-difluoroacrylates were obtained in high yields with high Z
      selectivity. Additionally, trialkylaluminum reagents were also found to be good
      nucleophiles, the corresponding addition-elimination products being afforded in
      good yields but with low stereoselectivity.

PMID- 18095705
TI  - Zigzag molecules from pyrene-modified carbazole oligomers: synthesis,
      characterization, and application in OLEDs.
AB  - A series of monodisperse, pyrene-modified oligocarbazoles were synthesized and
      fully characterized. Carbazoles were linked by ethynylene through the 3- and 6
      positions, forming a zigzag molecular backbone and stable, size-independent
      absorption, and emission were observed from these oligomers in solutions because
      their conjugation length was confined. Oligomers with pyrene exhibited much
      higher fluorescence quantum yields than those of oligomers without it. Different
      positions of pyrene in the oligocarbazole main chain resulted in a remarkable
      change in absorption and emission spectra. Moreover, devices with four different
      architectures (types 1-4) based on these oligomers were fabricated and
      investigated. Pyrene-modified carbazole oligomers exhibited bifunctional
      properties (light-emitting and hole-transport). Moreover, these devices showed
      moderate performances; for example,the device based on Cz3PyCz3 presented an
      external quantum efficiency of 0.69% and a maximum brightness of 1782 cd/m2 at
      13.5 V, which indicated these oligomers were promising optoelectric materials.

PMID- 18095706
TI  - Intramolecular hydrogen bonding and anion binding of N-benzamido-N'
      benzoylthioureas.
AB  - N-(p-Dimethylamino)benzoyl-N'-phenylthiourea as an N-acylthiourea is known to be
      unable to bind anions due to a strong intramolecular hydrogen bond (IHB). We show
      here that by inserting an amido group in the N'-phenyl side the newly designed N
      benzamido-N'-benzoylthioureas, despite this IHB too, bind strongly to anions with
      binding constants on the order of 10(6)-10(7) mol(-1) L. Results suggest that
      potential anion receptors or organocatalysts could be developed on the basis of
      this framework with a wide structural diversity.

PMID- 18095707
TI  - Chiral N-heterocyclic carbene--Pd(0)-catalyzed asymmetric diamination of
      conjugated dienes and triene.
AB  - Studies show that a variety of conjugated dienes and triene can be
      enantioselectively diaminated using di-tert-butyldiaziridinone as nitrogen source
      and chiral N-heterocyclic carbene-Pd(0) complex as catalyst in good
      enantioselectivity (62-91% ee) with high regio- and diastereoselectivity.

PMID- 18095708
TI  - Nonaromatic corroles: regioselectivity of electrophilic substitution.
AB  - Ring contraction of nickel meso-tetraarylporphyrins produced nonaromatic divalent
      corroles bearing a benzoyloxy function. We investigated their reactivity under
      electrophilic conditions: formylation, halogenation, nitration. We also found
      that the benzoate function could be eliminated to afford deoxocorroles, and we
      tested the formylation and nitration in this deoxo series. These corroles were
      generally very stable under the reaction conditions, and in both series, the
      directly bonded pyrroles were the most reactive. The nitration reaction produced
      a series of corrole dimers via electron transfer initiated coupling.

PMID- 18095709
TI  - Synthesis of diazatricyclic core of Madangamines from cis-perhydroisoquinolines.
AB  - Synthesis of the tricyclic core of madangamine alkaloids has been achieved in a
      10-step sequence starting from a 4-(aminomethyl)anisole derivative. A Birch
      reduction and acylation with cyanoacetic acid followed by an intramolecular
      Michael process renders a polyfunctionalized cis-perhydroisoquinoline. A
      diastereoselective allylation and reduction of amide, nitrile, and ketone groups
      leads to a bicyclic alcohol, which undergoes aminocyclization through the nosyl
      derivative to the diazatricyclic ring.

PMID- 18095710
TI  - Polymerization properties of the Thermotoga maritima actin MreB: roles of
      temperature, nucleotides, and ions.
AB  - MreB is a bacterial orthologue of actin that affects cell shape, polarity, and
      chromosome segregation. Although a significant body of work has explored its
      cellular functions, we know very little about the biochemical behavior of MreB.
      We have cloned, overexpressed in Escherichia coli, and purified untagged MreB1
      from Thermotoga maritima. We have characterized the conditions that regulate its
      monomer-to-polymer assembly reaction, the critical concentrations of that
      reaction, the manner in which MreB uses nucleotides, its stability, and the
      structure of the assembled polymer. MreB requires a bound purine nucleotide for
      polymerization and rapidly hydrolyzes it following assembly. MreB assembly
      contains two distinct components, one that does not require divalent cations and
      one that does, which may comprise the nucleation and elongation phases of
      assembly, respectively. MreB assembly is strongly favored by increasing
      temperature or protein concentration but inhibited differentially by high
      concentrations of monovalent salts. The polymerization rate increases and the
      bulk critical concentration decreases with increasing temperature, but in
      contrast to previous reports, MreB is capable of polymerizing across a broad
      range of temperatures. MreB polymers are shorter and stiffer and scatter more
      light than eukaryotic actin filaments. Due to rapid ATP hydrolysis and phosphate
      release, we suggest that most assembled MreB in cells is in the ADP-bound state.
      Because of only moderate differences between the ATP and ADP critical
      concentrations, treadmilling may occur, but we do not predict dynamic instability
      in cells. Because of the relatively low cellular concentration of MreB and the
      observed structural properties of the polymer, a single MreB assembly may exist
      in cells.

PMID- 18095711
TI  - Fibroblast activation protein peptide substrates identified from human collagen I
      derived gelatin cleavage sites.
AB  - A highly consistent trait of tumor stromal fibroblasts is the induction of the
      membrane-bound serine protease fibroblast activation protein-alpha (FAP), which
      is overexpressed on the surface of reactive stromal fibroblasts present within
      the stroma of the majority of human epithelial tumors. In contrast, FAP is not
      expressed by tumor epithelial cells or by fibroblasts or other cell types in
      normal tissues. The proteolytic activity of FAP, therefore, represents a
      potential pan-tumor target that can be exploited for the release of potent
      cytotoxins from inactive prodrugs consisting of an FAP peptide substrate coupled
      to a cytotoxin. To identify FAP peptide substrates, we used liquid chromatography
      tandem mass spectroscopy based sequencing to generate a complete map of the FAP
      cleavage sites within human collagen I derived gelatin. Positional analysis of
      the frequency of each amino acid at each position within the cleavage sites
      revealed FAP consensus sequences PPGP and (D/E)-(R/K)-G-(E/D)-(T/S)-G-P. These
      studies further demonstrated that ranking cleavage sites based on the magnitude
      of the LC/MS/MS extracted ion current predicted FAP substrates that were cleaved
      with highest efficiency. Fluorescence-quenched peptides were synthesized on the
      basis of the cleavage sites with the highest ion current rankings, and kinetic
      parameters for FAP hydrolysis were determined. The substrate DRGETGP, which
      corresponded to the consensus sequence, had the lowest Km of 21 microM. Overall
      the Km values were relatively similar for both high and low ranked substrates,
      whereas the kcat values differed by up to 100-fold. On the basis of these
      results, the FAP consensus sequences are currently being evaluated as FAP
      selective peptide carriers for incorporation into FAP-activated prodrugs.

PMID- 18095712
TI  - Kinetic and structural analysis of bisubstrate inhibition of the Salmonella
      enterica aminoglycoside 6'-N-acetyltransferase.
AB  - Aminoglycosides are antibacterial compounds that act by binding to the A site of
      the small 30S bacterial ribosomal subunit and inhibiting protein translation.
      Clinical resistance to aminoglycosides is generally the result of the expression
      of enzymes that covalently modify the antibiotic, including phosphorylation,
      adenylylation, and acetylation. Bisubstrate analogs for the aminoglycoside N
      acetyltransferases are nanomolar inhibitors of Enterococcus faecium AAC(6')-Ii.
      However, in the case of the Salmonella enterica aac(6')-Iy-encoded aminoglycoside
      N-acetyltransferase, we demonstrate that a series of bisubstrate analogs are only
      micromolar inhibitors. In contrast to studies with AAC(6')-Ii, the inhibition
      constants toward AAC(6')-Iy are essentially independent of both the identity of
      the aminoglycoside component of the bisubstrate and the number of carbon atoms
      that are used to link the CoA and aminoglycoside components. The patterns of
      inhibition suggest that the CoA portion of the bisubstrate analog can bind to the
      enzyme-aminoglycoside substrate complex and that the aminoglycoside portion can
      bind to the enzyme-CoA product complex. However, at the high concentrations of
      bisubstrate analog used in crystallization experiments, we could crystallize and
      solve the three-dimensional structure of the enzyme-bisubstrate complex. The
      structure reveals that both the CoA and aminoglycoside portions bind in
      essentially the same positions as those previously observed for the enzyme-CoA
      ribostamycin complex, with only a modest adjustment to accommodate the "linker".
      These results are compared to previous studies of the interaction of similar
      bisubstrate analogs with other aminoglycoside N-acetyltransferases.

PMID- 18095713
TI  - Chirality-sensing supramolecular systems.

PMID- 18095714
TI  - Potassium organotrifluoroborates: new perspectives in organic synthesis.

PMID- 18095715
TI  - Water as an active constituent in cell biology.

PMID- 18095716
TI  - Protic ionic liquids: properties and applications.

PMID- 18095717
TI  - DNA biosensors and microarrays.

PMID- 18095719
TI  - Role of phenol derivatives in the formation of silver nanoparticles.
AB  - We demonstrate that dihydroxy benzenes are excellent reducing agents and may be
      used to reduce silver ions to synthesize stable silver nanoparticles in air
      saturated aqueous solutions. The formation of Ag nanoparticles in deaerated
      aqueous solution at high pH values suggests that the reduction of silver ions
      occurs due to oxidation of dihydroxy benzenes and probably on the surface of
      Ag2O. Pulse radiolysis studies show that the semi-quinone radical does not
      participate in the reduction of silver ions at short time scales. Nevertheless,
      results show that primary intermediates undergo slower transformation in the
      presence of dihydroxy benzenes than in their absence. This slow transformation
      eventually leads to the formation of silver nanoparticles. The Ag nanoparticles
      were characterized by UV-vis absorption spectroscopy, X-ray diffraction (XRD),
      and transmission electron microscopy (TEM). XRD and TEM techniques showed the
      presence of Ag nanoparticles with an average size of 30 nm.

PMID- 18095720
TI  - Diffusion of PEG confined between lamellae of negatively magnetically aligned
      bicelles: pulsed field gradient 1H NMR measurements.
AB  - The diffusion of various molecular weight poly(ethyleneglycol)s (PEG) confined
      between the lamellae of magnetically aligned bicelles has been measured using
      stimulated echo (STE) pulsed field gradient (PFG) 1H nuclear magnetic resonance
      (NMR) spectroscopy. Bicelles were formulated to contain
      dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylglycerol (DMPG),
      and dihexanoylphosphatidylcholine (DHPC) in the proportion DMPG/DMPC = 0.05 and q
      = (DMPC + DMPG)/DHPC = 4.5. PEG diffusion within the interlamellar spaces between
      such bicelles was found to be unrestricted over diffusion distances of tens of
      microns. Two confinement regimes could be differentiated according to the
      dependence of the reduced PEG diffusivity D/D0, where D0 is the unconfined PEG
      diffusion coefficient, on the relative confinement Rh/H, where Rh is the
      unperturbed hydration radius of the particular PEG and H approximately 60 A is
      the separation between apposing lamellae of the magnetically aligned bicelles. In
      the regime Rh/H < 0.4, the reduced PEG diffusivity was altered only in proportion
      to the viscosity increase associated with the bicelle dispersion relative to bulk
      solution. In the regime Rh/H > 0.4, the reduced PEG diffusivity scaled as (Rh/H)
      2/3, in agreement with scaling theories for confined polymers.

PMID- 18095718
TI  - Lamellarins and related pyrrole-derived alkaloids from marine organisms.

PMID- 18095721
TI  - Photolytic metallization of au nanoclusters and electrically conducting
      micrometer long nanostructures on a DNA scaffold.
AB  - An electroless, photolytic method is described to synthesize Au nanoclusters and
      electrically conductive, micronmeter long nanostructures on DNA. Electrical
      characterization indicates that the Au nanostructures are continuous, exhibiting
      Ohmic behavior with very low contact resistance with the electrodes. The
      nanoclusters have a size of 10-40 nm, and the nanostructure have a diameter of 40
      70 nm with resistivity comparable to that of pure metal. The method is highly
      selective with deposition confined to the DNA template.

PMID- 18095722
TI  - Single-molecular-level study of claudin-1-mediated adhesion.
AB  - Claudins are proteins that are selectively expressed at tight junctions (TJs) of
      epithelial cells where they play a central role in regulating paracellular
      permeability of solutes across epithelia. However, the role of claudins in
      intercellular adhesion and the mechanism by which they regulate the diffusion of
      solutes are poorly understood. Here, using single molecule force spectroscopy,
      the kinetic properties and adhesion strength of homophilic claudin-1 interactions
      were probed at the single-molecule level. Within the range of tested loading
      rates (10(3)-10(5) pN/s), our results showed that homophilic claudin-1
      interactions have a reactive compliance of 0.363 +/- 0.061 nm and an unstressed
      dissociation rate of 1.351 +/- 1.312 s-1. This is more than 100-fold greater than
      that of E-cadherin. The weak and short-lived interactions between claudin-1
      molecules make them highly unstable and dynamic in nature. Such a dynamic
      interaction is consistent with a model where breaking and resealing of TJ strands
      regulate the paracellular diffusion of solutes.

PMID- 18095723
TI  - Dark-to-bright optical responses of liquid crystals supported on solid surfaces
      decorated with proteins.
AB  - Protein assays are critical analytical tools performed in various biochemical
      laboratories to quantify the concentration of proteins. In this study, we report
      the optical responses of a thin layer of liquid crystals supported on glass
      slides decorated with proteins and the utility of this phenomenon as a new "all
      or-nothing" type of protein assay. It was found that the orientations of liquid
      crystals are very sensitive to the concentration of protein solution applied to
      the surface. When the protein concentration exceeds a critical value (IgG 5.0
      microg/mL, BSA 6.0 microg/mL, FTIC-anti-biotin 0.40 microg/mL, and FITC-anti-IgG
      0.37 microg/mL), the thin layer of liquid crystals gives a very sharp dark-to
      bright optical response within a small concentration range. This characteristic
      is not observed in any traditional protein assays, which are based on the
      adsorption of UV or visible light. The optical response is also very precise and
      reproducible. It is not affected by the thickness of the liquid crystal cell or
      the amount of organosilanes coated on the glass slides. The liquid crystal-based
      protein assay may be very useful for screening purposes, especially when a simple
      positive or negative answer is desired.

PMID- 18095724
TI  - Liposome-recruited activity of oxidized and fragmented superoxide dismutase.
AB  - The peptide fragment of H2O2-treated Cu,Zn-superoxide dismutase (SOD) was found
      to be reactivated with liposomes prepared by 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC). The fragmentation of SOD was observed by 2 mM H2O2
      treatment as well as by SOD inactivation and the loss of an alpha-helix in the
      neighborhood of its activity center. The H2O2-treated SOD, which lost its
      activity at different incubation times, was dramatically reactivated only by
      adding POPC liposomes, resulting in 1.3-2.8 times higher enzymatic activity. The
      ultrafiltration analysis of H2O2-treated SOD co-incubated with liposomes shows
      that some specific peptide fragments of the oxidized SOD can interact with POPC
      liposomes. A comparison of the fractions detected in reverse-phase chromatography
      shows that specific SOD fragments are able to contribute to the reactivation of
      oxidized and fragmented SOD in the presence of POPC liposomes. The liposomes can
      recruit the potentially active fragment of SOD among the lethally damaged SOD
      fragments to elucidate the antioxidative function.

PMID- 18095725
TI  - On the anomalous adsorption of [Pd(edta)]2- at the water/Goethite interface:
      spectroscopic evidence for two types of surface complexes.
AB  - The structure of palladium(II) ethylenediaminetetraacetate (edta) in aqueous
      solutions and its adsorption on the surface of goethite (alpha-FeOOH) were
      studied using extended X-ray absorption fine structure spectroscopy and
      attenuated total reflection Fourier transform infrared spectroscopy. The obtained
      results show that in aqueous solutions, Pd-edta exists as a 1:1 complex,
      [Pd(edta)]2-, with edta acting as a quadridentate ligand. On the surface of
      goethite, [Pd(edta)]2- forms two different types of complexes over a pH range of
      3.40-8.12. At pH < 5, [Pd(edta)]2- adsorbs as an outer-sphere species with
      possible hydrogen bonding. At higher pH values, the formation of inner-sphere
      complexes of the cation-type sets in after a cleavage of one glycinate ring and
      the formation of an (edta)Pd-O-Fe linkage.

PMID- 18095726
TI  - Novel film-calliper method of measuring the contact angle of colloidal particles
      at liquid interfaces.
AB  - A simple and reliable film-calliper method of measuring the particle contact
      angle at the water-air (oil) interface in real time has been developed. Its
      applicability to submicrometer and micrometer latex and silica particles is
      demonstrated.

PMID- 18095727
TI  - Electroosmotic flow in nanotubes with high surface charge densities.
AB  - The ion distribution and electroosmotic flow of sodium chlorine solutions
      confined in cylindrical nanotubes with high surface charge densities are studied
      with molecular dynamics (MD). To obtain a more practical physical model for
      electroosmotic driven flow in a nanoscale tube, the MD simulation process
      consists of two steps. The first step is used to equilibrate the system and to
      obtain a more realistic ion distribution in the solution under different surface
      charge densities. Then, an external electric field is acted to drive the liquids.
      The simulation results indicate that with the increase of the surface charge
      density, both the thickness of the electric double layer and the peak height of
      the counterion density increase. However, the phenomenon of charge inversion does
      not occur even as the surface charge density increases to -0.34 C/m2, which is
      rather difficult to reach for real materials in practical situations. This
      simulation result confirms the recent experimental observation that monovalent
      ions of sufficiently high concentrations can reduce or even cancel the charge
      inversion occurred in the case of multivalent ions [F. H. J. van der Heyden et
      al. Phys. Rev. Lett. 2006, 96, 224502].

PMID- 18095728
TI  - WS2 nanobuds as a new hybrid nanomaterial.
AB  - We report on the first inorganic nanobuds: WS2 nanotubes decorated with fullerene
      like particles. They were synthesized by sulfurization of W5O14 nanowires. The
      fullerene-like particles nucleate in surface corrugations of the nanowires and
      grow by a diffusion process simultaneously with the transformation of nanowires
      into hollow multiwall nanotubes. Electron microscopy data are correlated with
      details of the transformation process revealing the possible mechanism of the
      formation of these new complex nanomaterials.

PMID- 18095729
TI  - Silicon nanowires-based fluorescence sensor for Cu(II).
AB  - Si nanowires (SiNWs) were covalently modified by fluorescence ligand, N
      (quinoline-8-yl)-2-(3-triethoxysilyl-propylamino)-acetamide (QlOEt) and finally
      formed an optical sensor to realize a highly sensitive and selective detection
      for Cu(II). The QlOEt-modified SiNWs sensor has sensitivity for Cu(II) down to
      10(-8) M, which is more sensitive than QlOEt alone. Metal ions interferences have
      no observable effect on the sensitivity and selectivity of QlOEt-modified SiNWs
      sensor. The SiNWs-based fluorescence sensor is reversible by addition of acid to
      replace Cu(II). The sensing mechanisms of QlOEt-modified SiNWs to Cu(II) and the
      rationale for the increase in sensitivity and selectivity of QlOEt-modified SiNWs
      over QlOEt on Cu(II) are discussed. The current sensor structure may be
      extendable to other chemo- and biosensors, and even to nanosensors for direct
      detection of specific materials in intracellular environment.

PMID- 18095730
TI  - The effect of molecular orientation on the potential of porphyrin-metal contacts.
AB  - The effect of molecular orientation at metal contacts on interface properties was
      determined by examining the local work function of porphyrin on atomically smooth
      graphite. The orientation was varied by self-assembly from the vapor phase, and
      the local potential was quantified by Kelvin force microscopy (scanning surface
      potential microscopy). When the porphyrin ring is oriented parallel to the
      substrate, the surface work function is 50 mV less than that of the highly
      ordered pyrolytic graphite; in contrast, when the porphyrin molecular plane is
      oriented perpendicular to the substrate, the surface work function is unchanged.
      The orientation dependence of the surface work function is determined by the
      geometric relationships between the delocalized charge densities in the molecule
      and substrate and possible interface bonding. The differences in interface
      properties with molecular configuration have important design implications to
      molecular electronic and organic electronic devices.

PMID- 18095731
TI  - Control of surface migration of gold particles on Si nanowires.
AB  - On the surface of silicon nanowires (SiNWs) synthesized by gold (Au)-catalyzed
      chemical vapor deposition (CVD), Au particles 5-20 nm in diameter are formed if
      the growth conditions are within a specific range. We studied the mechanism of Au
      particle formation by growing SiNWs under different conditions, specifically by
      dynamically changing the growth parameters during the growth process. We show
      that insufficient supply of Si source to the Au-Si eutectic on top of the SiNWs
      enhances the migration of Au atoms on the surface of SiNWs in the form of Au-Si
      eutectic, which is precipitated on the surface as Au particles during cooling. We
      also show that using Au-Si eutectic on the surface of SiNWs as a catalyst enables
      one-step growth of branched SiNWs.

PMID- 18095732
TI  - Mobile iron nanoparticle and its role in the formation of SiO2 nanotrench via
      carbon nanotube-guided carbothermal reduction.
AB  - The detailed role of iron nanoparticles (NPs) involved with the formation of SiO2
      nanotrenches is revealed. The physical movements of iron NPs, such as levitation
      and adsorption, turn out to be responsible for the initiation of carbothermal
      reduction (C (carbon nanotube, s) + SiO2(s) <--> SiO(g) + CO(g)), which results
      in SiO2 nanotrenches that are fully guided by carbon nanotubes. Under the
      chemical vapor deposition condition with 0.1% of O2 gas, iron NPs are liberally
      levitated from SiO2/Si substrate then adsorbed on the sidewalls of carbon
      nanotubes. Depending on the numbers of iron NPs attached to carbon nanotubes, two
      different types of nanotrenches are determined. When multiple iron NPs are
      assembled on carbon nanotubes and involved in carbothermal reduction, aligned
      nanohole type of nanotrenches is produced (Type I). On the contrary, when single
      iron NPs initiate the carbothermal reduction, nanotrenches having smooth pathways
      and high shoulders are commonly formed (Type II).

PMID- 18095733
TI  - CO oxidation catalyzed by single-walled helical gold nanotube.
AB  - We study the catalytic capability of unsupported single-walled helical gold
      nanotubes Au(5,3) by using density functional theory. We use the CO oxidation as
      a benchmark probe to gain insights into high catalytic activity of the gold
      nanotubes. The CO oxidation, catalyzed by the Au(5,3) nanotube, proceeds via a
      two-step mechanism, CO + O2 --> CO2 +O and CO + O --> CO2. The CO oxidation is
      initiated by the CO + O2 --> OOCO --> CO2 + O reaction with an activation barrier
      of 0.29 eV. On the reaction path, a peroxo-type O-O-CO intermediate forms.
      Thereafter, the CO + O --> CO2 reaction proceeds along the reaction pathway with
      a very low barrier (0.03 eV). Note that the second reaction cannot be the
      starting point for the CO oxidation due to the energetically disfavored
      adsorption of free O2 on the gold nanotube. The high catalytic activity of the
      Au(5,3) nanotube can be attributed to the electronic resonance between electronic
      states of adsorbed intermediate species and Au atoms at the reaction site,
      particularly among the d states of Au atom and the antibonding 2pi* states of C-O
      and O1-O2, concomitant with a partial charge transfer. The presence of
      undercoordinated Au sites and the strain inherent in the helical gold nanotube
      also play important roles. Our study suggests that the CO oxidation catalyzed by
      the helical gold nanotubes is likely to occur at the room temperature.

PMID- 18095734
TI  - Two-dimensional photonic crystal resist membrane nanocavity embedding colloidal
      dot-in-a-rod nanocrystals.
AB  - A novel technique for the fabrication of photonic crystal (PC) nanocavities
      coupled with colloidal nanocrystals is presented. A waveguiding resist membrane
      embedding highly emitting dot-in-a-rod nanocrystals was patterned through e-beam
      lithography and released through wet etching process. The proposed approach makes
      the PC structure independent of fabrication imperfections induced by etching
      steps. Micro-photoluminescence spectra revealed degenerated resonant modes (Q
      factor approximately 700) whose fabrication-induced spectral splitting is
      comparable to the full width at half-maximum of the peaks. Active nanocavities
      tunable from visible to infrared spectral range on GaAs or Si substrates can be
      easily implemented by this technique.

PMID- 18095735
TI  - Ultralow thermal conductivity of isotope-doped silicon nanowires.
AB  - The thermal conductivity of silicon nanowires (SiNWs) is investigated by
      molecular dynamics (MD) simulation. It is found that the thermal conductivity of
      SiNWs can be reduced exponentially by isotopic defects at room temperature. The
      thermal conductivity reaches the minimum, which is about 27% of that of pure 28Si
      NW, when doped with 50% isotope atoms. The thermal conductivity of isotopic
      superlattice structured SiNWs depends clearly on the period of superlattice. At a
      critical period of 1.09 nm, the thermal conductivity is only 25% of the value of
      pure Si NW. An anomalous enhancement of thermal conductivity is observed when the
      superlattice period is smaller than this critical length. The ultralow thermal
      conductivity of superlattice structured SiNWs is explained with phonon spectrum
      theory.

PMID- 18095736
TI  - Solution control of radiative and nonradiative lifetimes: a novel contribution to
      quantum dot blinking suppression.
AB  - Time-correlated single photon counting methods are used with confocal microscopy
      and maximum likelihood estimation analysis to obtain fluorescence lifetime
      trajectories for single quantum dots with KHz update rates. This technique
      reveals that control of the solution environment can influence both radiative
      (k(rad)) and nonradiative (k(nonrad)) pathways for electron-hole recombination
      emission in a single quantum dot and provides a novel contribution mechanism to
      nearly complete suppression of quantum dot blinking, specifically by an increase
      in k(rad*).

PMID- 18095737
TI  - Hierarchical assembly of nanostructured organosilicate networks via
      stereocomplexation of block copolymers.
AB  - The effect of the stereochemistry of polylactide (PLA)-based block copolymers on
      templated inorganic nanostructures has been investigated from the self-assembly
      of a stereoisomer pair/organosilicate mixture followed by organosilicate
      vitrification and copolymer thermolysis. Isomeric PLA homopolymers, block
      copolymers, and a stereoblock copolymer were prepared by ring-opening
      polymerization of D-, L-, or rac-lactide using an organocatalytic catalyst. Both
      differential scanning calorimetry and atomic force microscopy showed the
      formation of a stereocomplex between enantiomeric stereoisomers, that is, block
      copolymer/block copolymer and block copolymer/homopolymer mixtures as well as a
      stereoblock copolymer. The unique noncovalent interactions driven by
      stereocomplexation of D- and L-lactide provided supramolecular structures with a
      hierarchical order as characterized by distinctive vertical and horizontal growth
      of toroidal nanostructured inorganic features. This study demonstrates the
      potential of hierarchically assembling suprastructures that bridge the nano- to
      mesoscale feature sizes in the design of tunable functional nanomaterials
      suitable for future applications of microelectronics, material science, and
      bioengineering.

PMID- 18095738
TI  - High capacity Li ion battery anodes using ge nanowires.
AB  - Ge nanowire electrodes fabricated by using vapor-liquid-solid growth on metallic
      current collector substrates were found to have good performance during cycling
      with Li. An initial discharge capacity of 1141 mA.h/g was found to be stable over
      20 cycles at the C/20 rate. High power rates were also observed up to 2C with
      Coulombic efficiency > 99%. Structural characterization revealed that the Ge
      nanowires remain intact and connected to the current collector after cycling.
      Nanowires connected directly to the current collector have facile strain
      relaxation and material durability, short Li diffusion distances, and good
      electronic conduction. Thus, Ge nanowire anodes are promising candidates for the
      development of high-energy-density lithium batteries.

PMID- 18095739
TI  - Single particle X-ray diffractive imaging.
AB  - In nanotechnology, strategies for the creation and manipulation of nanoparticles
      in the gas phase are critically important for surface modification and substrate
      free characterization. Recent coherent diffractive imaging with intense
      femtosecond X-ray pulses has verified the capability of single-shot imaging of
      nanoscale objects at suboptical resolutions beyond the radiation-induced damage
      threshold. By intercepting electrospray-generated particles with a single 15
      femtosecond soft-X-ray pulse, we demonstrate diffractive imaging of a nanoscale
      specimen in free flight for the first time, an important step toward imaging
      uncrystallized biomolecules.

PMID- 18095740
TI  - Crossover from Kondo-assisted suppression to co-tunneling enhancement of
      tunneling magnetoresistance via ferromagnetic nanodots in MgO tunnel barriers.
AB  - The dependence of the tunneling magnetoresistance (TMR) of planar magnetic tunnel
      junctions on the size of magnetic nanodots incorporated within MgO tunnel
      barriers is explored. At low temperatures, in the Coulomb blockade (CB) regime,
      for smaller nanodots the conductance of the junction is increased at low bias
      consistent with Kondo-assisted tunneling and the TMR is suppressed. For slightly
      larger nanodots but within the CB regime, the TMR is enhanced at low bias,
      consistent with co-tunneling. Magnetic tunnel junctions (MTJ) exhibit giant
      magnetoresistance in small magnetic fields that arises from the flow of spin
      polarized current through an ultrathin tunnel barrier separating two magnetic
      electrodes. The current through an MTJ device depends on the magnetic orientation
      of the electrodes and is typically higher when the electrode moments are parallel
      than when they are antiparallel. It has recently been demonstrated that the spin
      polarization of the tunneling current can be greatly enhanced by using
      crystalline tunnel barriers formed from MgO as compared with conventional
      amorphous barriers formed from alumina, due to spin filtering across the MgO
      layer. The magneto-transport properties of magnetic granular alloys and magnetic
      tunnel junction devices with magnetic nanodots embedded in amorphous dielectric
      matrices, and tunnel barriers, respectively, have been studied by several groups,
      but no systematic studies of the dependence on these properties on the nanodot
      size have been made.

PMID- 18095741
TI  - Formation and self-breaking mechanism of stable atom-sized junctions.
AB  - The self-breaking mechanism of gold junctions is studied by investigating
      stability of the atom-sized contacts. The single atom contact lifetime increases
      from about 0.02 to 200 s upon decreasing the junction stretching speed, while at
      the same time, the breaking force diminishes logarithmically. We find that the
      junction self-breaking processes involve sufficient atomic rearrangements, which
      thereby allow complete self-compensation of externally introduced strain at 0.8
      pm/s. The present results have important implications on fabrication of stable
      single molecule junctions.

PMID- 18095742
TI  - Intelligent risk communication: can it be improved?
AB  - Every year, regulators and scientists from academia and industry invest
      considerable time and effort into drug development, the assessment of safety, and
      subsequent risk-benefit communication. The observation of everyday medical
      practice, lay press releases and drug information indicates that all these
      efforts do not do justice to the work and effort invested. Risk communication is
      a complex scientific activity, which, when done properly, benefits patients, and
      when done poorly, may lead to harm. There is much misunderstanding and confusion
      even between professionals in communicating risk-benefit information, as the
      association of risk with drug treatment is a difficult concept to accept. It is
      apparent that the concept of intelligent risk-benefit communication has to be
      developed extensively on many levels and with the co-operation of everyone
      involved (patients, physicians, regulators, scientists, journalists, lawyers and
      the government). This article addresses some key aspects of dealing with the
      risks associated with drug treatment in everyday practice, as consideration of
      these risks may be of benefit to all concerned in the future.

PMID- 18095744
TI  - Methods for causality assessment of adverse drug reactions: a systematic review.
AB  - Numerous methods for causality assessment of adverse drug reactions (ADRs) have
      been published. The aim of this review is to provide an overview of these methods
      and discuss their strengths and weaknesses. We conducted electronic searches in
      MEDLINE (via PubMed), EMBASE and the Cochrane databases to find all assessment
      methods. Thirty-four different methods were found, falling into three broad
      categories: expert judgement/global introspection, algorithms and probabilistic
      methods (Bayesian approaches). Expert judgements are individual assessments based
      on previous knowledge and experience in the field using no standardized tool to
      arrive at conclusions regarding causality. Algorithms are sets of specific
      questions with associated scores for calculating the likelihood of a cause-effect
      relationship. Bayesian approaches use specific findings in a case to transform
      the prior estimate of probability into a posterior estimate of probability of
      drug causation. The prior probability is calculated from epidemiological
      information and the posterior probability combines this background information
      with the evidence in the individual case to come up with an estimate of
      causation. As a result of problems of reproducibility and validity, no single
      method is universally accepted. Different causality categories are adopted in
      each method, and the categories are assessed using different criteria. Because
      assessment methods are also not entirely devoid of individual judgements, inter
      rater reliability can be low. In conclusion, there is still no method universally
      accepted for causality assessment of ADRs.

PMID- 18095743
TI  - Benefits and risks of antipsychotic polypharmacy: an evidence-based review of the
      literature.
AB  - Combination antipsychotic prescription is an increasingly common practice in
      clinical psychiatry. This clinical practice is at odds with clinical guidelines
      promoting antipsychotic monotherapy. Moreover, there has been increased concern
      over the safety profile of atypical antipsychotics in the last 10-15 years. We
      reviewed the literature on antipsychotic combinations with a focus on safety and
      efficacy. Multiple electronic database searches were complemented by relevant
      bibliography cross-checking and expert discussions. The review showed a
      literature that is dominated by case reports and uncontrolled studies.
      Polypharmacy was unequally studied, with some recent combinations (i.e. clozapine
      and risperidone) being extensively, albeit inconclusively, studied and other more
      commonly used combinations (first- with second-generation agents) receiving
      little attention. From an evidence-based perspective, further trials of
      antipsychotic association of sufficient power to address safety issues are needed
      before recommending any antipsychotic combination. Particular weaknesses of the
      present literature are low number of participants, lack of adequate control of
      confounding variables, short duration of experimental follow-up and inadequate
      monitoring of potential adverse effects.

PMID- 18095745
TI  - Data resources for investigating drug exposure during pregnancy and associated
      outcomes: the General Practice Research Database (GPRD) as an alternative to
      pregnancy registries.
AB  - Pregnancy registries are the most commonly used data resource for the post
      marketing surveillance of drug teratogenicity. However, the limited sample size
      and potential selection bias in these registries has led us to investigate the
      potential of the UK General Practice Research Database (GPRD) as an alternative
      data source for monitoring drug safety during pregnancy. In addition, a
      literature review identified further observational data sources that monitor
      pregnancy outcomes for future evaluation. Initial feasibility studies focused on
      the ability of the GPRD to capture pregnancy outcomes for a range of drug class
      exposures, all of which are currently under investigation in pregnancy
      registries, during pregnancy. The comparator pregnancy registries were identified
      via a MEDLINE search, whilst eligible pregnancies, in which women received one or
      more prescriptions for the drug of interest during pregnancy, were identified in
      the GPRD using the mother-baby link. The number of pregnancy outcomes following
      exposure to medication for a range of conditions with varying prevalence,
      including depression, migraine, epilepsy, herpes simplex and HIV, captured by the
      two data sources were compared. For depression, a relatively prevalent condition,
      the GPRD recorded the same number of mean annual intrauterine exposures to
      fluoxetine as the pregnancy registry (118 exposures/year). Ascertainment of
      intrauterine exposure to drug treatments for less prevalent conditions was found
      to be higher for the pregnancy registries than the GPRD; for the older
      antiepileptic drugs (valproate and carbamazepine), the pregnancy registry
      recorded between four and five times as many mean annual exposures as the GPRD.
      Virtually no antiretroviral exposures (three) were identified during the time
      period of interest on the GPRD, compared with 3946 in the Antiretroviral
      Pregnancy Registry. Data from the GPRD meet established criteria for evaluating
      outcomes of pregnancy. For prevalent conditions, it has the potential to replace
      or work alongside standard pregnancy registries and the alternative data sources
      identified. Further studies are now needed to assess its ability to replicate
      known teratogenic associations.

PMID- 18095746
TI  - Orlistat-associated adverse effects and drug interactions: a critical review.
AB  - Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal
      lipases. In light of the recent US FDA approval of the over-the-counter sale of
      orlistat (60 mg three times daily), clinicians need to be aware that its use may
      be associated with less well known, but sometimes clinically relevant, adverse
      effects. More specifically, the use of orlistat has been associated with several
      mild-to-moderate gastrointestinal adverse effects, such as oily stools,
      diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic
      adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver
      failure) have been reported. However, the effects of orlistat on non-alcoholic
      fatty liver disease are beneficial. Orlistat-induced weight loss seems to have
      beneficial effects on blood pressure. No effect has been observed on calcium,
      phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers.
      Interestingly, the use of orlistat has been associated with rare cases of acute
      kidney injury, possibly due to the increased fat malabsorption resulting from the
      inhibition of pancreatic and gastric lipase by orlistat, leading to the formation
      of soaps with calcium and resulting in increased free oxalate absorption and
      enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate
      metabolism. No significant effect on cancer risk has been reported with
      orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin,
      amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting
      their bioavailability and effectiveness. This review considers orlistat-related
      adverse effects and drug interactions. The clinical relevance and pathogenesis of
      these effects is also discussed.

PMID- 18095747
TI  - Randomized, double-blind, crossover study to investigate the effect of
      rivaroxaban on QT-interval prolongation.
AB  - BACKGROUND: Rivaroxaban (BAY 59-7939) is a novel, oral, direct Factor Xa
      inhibitor in advanced clinical development for the prevention and treatment of
      thromboembolic disorders. Unwanted pro-arrhythmic effects are a common reason for
      drugs failing to gain regulatory approval; these properties can be detected by
      assessing the effect of the drug on the QT interval. OBJECTIVE: This study was
      performed, in accordance with International Conference on Harmonisation (ICH) E14
      guidance, to assess whether rivaroxaban prolongs the QT interval. STUDY DESIGN:
      This was a prospective, randomized, double-blind, double-dummy, four-way
      crossover study. SETTING: The study was conducted at a clinical pharmacology
      research unit. SUBJECTS: Healthy male and female subjects (n = 54) aged > or =50
      years were enrolled and remained in the study unit for 3 days for each treatment.
      Of these, 50 patients were eligible for the QT analysis. INTERVENTION: Subjects
      received single oral doses of rivaroxaban 45 mg or 15 mg, moxifloxacin 400 mg
      (positive control), or placebo. OUTCOME MEASURES: Multiple ECGs were taken at
      frequent intervals after drug administration, and the QT interval was measured
      manually under blinded conditions at a central laboratory. The Fridericia
      correction formula (QTcF) was used to correct the QT interval for heart rate. The
      primary outcome was the effect of rivaroxaban or moxifloxacin on the placebo
      subtracted QTcF 3 hours after administration. The frequency of outlying QTcF
      values and the tolerability of the treatments were also assessed. RESULTS: All
      treatments were well tolerated and had no effect on heart rate. Moxifloxacin
      established the required assay sensitivity; placebo-subtracted QTcF 3 hours after
      moxifloxacin administration was prolonged by 9.77 ms (95% CI 7.39, 12.15).
      Placebo-subtracted QTcF values 3 hours after rivaroxaban administration were 
      0.91 ms (95% CI -3.33, 1.52) and -1.83 ms (95% CI -4.19, 0.54) with rivaroxaban
      45 mg and 15 mg, respectively. QTcF was not prolonged with rivaroxaban at any
      time, and the frequency of outlying results with rivaroxaban and placebo was
      similar. CONCLUSION: This thorough QT study, which was performed in accordance
      with ICH E14 guidelines, shows that rivaroxaban does not prolong the QTc
      interval. Therefore, the potential of rivaroxaban for the prevention and
      treatment of thromboembolic disorders, including chronic cardiovascular
      disorders, can be investigated in appropriate clinical studies without the need
      for intensive monitoring of the QTc interval.

PMID- 18095749
TI  - Discovery and development of the epothilones : a novel class of antineoplastic
      drugs.
AB  - The epothilones are a novel class of antineoplastic agents possessing antitubulin
      activity. The compounds were originally identified as secondary metabolites
      produced by the soil-dwelling myxobacterium Sorangium cellulosum. Two major
      compounds, epothilone A and epothilone B, were purified from the S. cellulosum
      strain So ce90 and their structures were identified as 16-member macrolides.
      Initial screening with these compounds revealed a very narrow and selective
      antifungal activity against the zygomycete, Mucor hiemalis. In addition, strong
      cytotoxic activity against eukaryotic cells, mouse L929 fibroblasts and human T
      24 bladder carcinoma cells was observed. Subsequent studies revealed that
      epothilones induce tubulin polymerization and enhance microtubule stability.
      Epothilone-induced stabilisation of microtubules was shown to cause arrest at the
      G2/M transition of the cell cycle and apoptosis. The compounds are active against
      cancer cells that have developed resistance to taxanes as a result of acquisition
      of beta-tubulin overexpression or mutations and against multidrug-resistant cells
      that overexpress P-glycoprotein or multidrug resistance-associated protein. Thus,
      epothilones represent a new class of antimicrotubule agents with low
      susceptibility to key tumour resistance mechanisms. More recently, a range of
      synthetic and semisynthetic epothilone analogues have been produced to further
      improve the adverse effect profile (or therapeutic window) and to maximize
      pharmacokinetic and antitumour properties. Various epothilone analogues have
      demonstrated activity against many tumour types in preclinical studies and
      several compounds have been and still are being evaluated in clinical trials.
      This article reviews the identification and early molecular characterization of
      the epothilones, which has provided insight into the mode of action of these
      novel antitumour agents in vivo.

PMID- 18095748
TI  - Effects of rivastigmine on tremor and other motor symptoms in patients with
      Parkinson's disease dementia: a retrospective analysis of a double-blind trial
      and an open-label extension.
AB  - BACKGROUND AND AIM: Rivastigmine is now widely approved for the treatment of mild
      to moderately severe dementia in Parkinson's disease (PDD). However, since
      anticholinergic drugs have a role in the management of tremor in patients with
      Parkinson's disease (PD), concerns have been raised that the use of cholinergic
      drugs might worsen PD. The current analyses were performed to examine the
      potential of rivastigmine to affect tremor and other motor symptoms in patients
      with PDD. METHODS: The safety profile of rivastigmine was evaluated using a
      database from a 24-week, randomized, double-blind, placebo-controlled trial in
      541 PDD patients (362 randomized to rivastigmine, 179 to placebo), and 334 PDD
      patients who subsequently entered an open-label 24-week extension on
      rivastigmine. RESULTS: During the double-blind trial, the adverse event (AE) of
      emerging or worsening tremor was reported in 10.2% of patients in the
      rivastigmine group, compared with 3.9% in the placebo group (p = 0.012). Tremor
      was most frequently reported during the titration phase of rivastigmine
      treatment, although this was not reflected in total motor Unified Parkinson's
      Disease Rating Scale (UPDRS) part III scores. Dose dependence of this AE was not
      observed. At the end of the double-blind phase, six (1.7%) rivastigmine-treated
      patients had discontinued the study because of tremor. In the open-label
      extension in which all patients received rivastigmine, tremor was reported by
      6.9% of patients: 3.8% and 12.2% of whom had previously received double-blind
      rivastigmine and placebo, respectively (p = 0.006), suggesting that first
      exposure to rivastigmine leads to a transient increase in tremor. Three (0.9%) of
      the 334 patients who entered the open-label extension phase discontinued because
      of tremor. Incidences of worsening parkinsonism, bradykinesia and rigidity were
      all <5% in both treatment groups (all p-values not statistically significant,
      rivastigmine vs placebo). In the 48-week observation of rivastigmine treatment,
      there was no evidence of adverse long-term motor outcomes. Post-hoc analysis
      showed that similar improvements in the symptoms of dementia, including the
      ability to perform activities of daily living, were seen regardless of whether
      exacerbation of tremor was reported during the study. CONCLUSION: Rivastigmine
      did not induce clinically significant exacerbation of motor dysfunction in
      patients with PDD. Rest tremor incidence as an AE was a transient phenomenon
      during dose titration of rivastigmine. There was no indication that exposure to
      long-term rivastigmine was associated with a worsening of PD.

PMID- 18095750
TI  - Botulinum toxin for pain.
AB  - Botulinum toxin (BTX) injection is being increasingly used 'off label' in the
      management of chronic pain. Data support the hypothesis of a direct analgesic
      effect of BTX, different to that exerted on muscle. Although the pain-reducing
      effect of BTX is mainly due to its ability to block acetylcholine release at the
      synapse, other effects on the nervous system are also thought to be involved. BTX
      affects cholinergic transmission in both the somatic and the autonomic nervous
      systems. Proposed mechanisms of action of BTX for pain relief of trigger points,
      muscular spasms, fibromyalgia and myofascial pain include direct action on muscle
      and indirect effects via action at the neuromuscular junction. Invitro and invivo
      data have shown that BTX has specific antinociceptive activity relating to its
      effects on inflammation, axonal transport, ganglion inhibition, and spinal and
      suprasegmental level inhibition. Our review of the mechanisms of action,
      efficacy, administration techniques and therapeutic dosage of BTX for the
      management of chronic pain in a variety of conditions shows that although
      muscular tone and movement disorders remain the most important therapeutic
      applications for BTX, research suggests that BTX can also provide benefits
      related to effects on cholinergic control of the vascular system, autonomic
      function, and cholinergic control of nociceptive and antinociceptive systems.
      Furthermore, it appears that BTX may influence the peripheral and central nervous
      systems. The therapeutic potential of BTX depends mainly on the ability to
      deliver the toxin to the target structures, cholinergic or otherwise. Evidence
      suggests that BTX can be administered at standard dosages in pain disorders,
      where the objective is alteration of muscle tone. For conditions requiring an
      analgesic effect, the optimal therapeutic dosage of BTX remains to be defined.

PMID- 18095751
TI  - Efficacy of a mucoadhesive patch compared with an oral solution for treatment of
      aphthous stomatitis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy and
      tolerability of a mucoadhesive patch compared with a pain-relieving oral solution
      for the treatment of aphthous stomatitis. METHODS: Patients with active aphthous
      stomatitis were randomly treated either once a day with a mucoadhesive patch
      containing citrus oil and magnesium salts (n = 26) or three times a day with an
      oral solution containing benzocaine and compound benzoin tincture (n = 22). All
      patients were instructed to apply the medication until pain had resolved, and
      completed a questionnaire detailing multiple clinical parameters followed by an
      evaluation of the treatment. RESULTS: The mucoadhesive patch was found to be more
      effective than the oral solution in terms of healing time (mean +/- SD: 36.0 +/-
      22.8 hours vs 134.7 +/- 57.7, p < 0.001) and pain intensity after 12 and 24 hours
      (3.7 +/- 2.8 vs 6.3 +/- 2.6, p = 0.003, and 2.3 +/- 2.7 vs 5.7 +/- 2.5, p <
      0.001, respectively). Local adverse effects 1 hour after treatment were
      significantly (p < 0.01) less frequent among the mucoadhesive patch patients
      compared with the oral solution patients. CONCLUSIONS: The mucoadhesive patch was
      found to be significantly more effective and better tolerated than the oral
      solution in the treatment of aphthous stomatitis.

PMID- 18095754
TI  - [Thirty years of the "Asociacion Espanola de Micologia"].
AB  - Since the foundation of the "Asociacion Espanola de Micologia" thirty years ago,
      we have consolidated the Spanish mycological community and also witnessed
      remarkable changes, not only in the Spanish society but in the scientific
      community as a whole. As it usually happens to human beings, during this time the
      "Asociacion Espanola de Micologia" has matured transforming itself into a solid
      scientific society. However, the "Asociacion Espanola de Micologia" will have to
      continue its transformation to adapt to new changes. This article shows the most
      relevant aspects in the history of the "Asociacion Espanola de Micologia" as well
      as new challenges that the society might face in the future.

PMID- 18095752
TI  - Pharmacology and metabolism of renzapride : a novel therapeutic agent for the
      potential treatment of irritable bowel syndrome.
AB  - BACKGROUND AND OBJECTIVE: Renzapride (ATL-1251), a novel benzamide, is currently
      under clinical development for the treatment of irritable bowel syndrome (IBS).
      Previous in vitro and in vivo experimental studies have characterized renzapride
      as a full serotonin 5-HT(4) receptor agonist on the gut and a 5-HT(3) receptor
      antagonist. Clinical studies have confirmed the therapeutic efficacy,
      tolerability and safety of renzapride in patients with constipation-predominant
      IBS. This study set out to characterize the pharmacological profile of renzapride
      and its potential metabolic products at both 5-HT and other monoamine receptors
      in the gut. METHODS: The affinity of renzapride, its (+) and (-) enantiomers, and
      its primary metabolite, renzapride N-oxide and its enantiomers, for serotonin
      receptors was assessed by means of in vitro radioligand binding inhibition
      studies. After membranes prepared from animal tissue or membranes of cell lines
      transfected with cloned human receptors had been incubated with radiolabelled
      ligand with high affinity for a specific receptor, renzapride was added to
      competitively inhibit this binding. Levels of bound radioligand were measured by
      filtration and counting of the bound radioactivity. In instances where >50%
      inhibition of radioligand binding had occurred, the inhibition constant (K(i))
      was calculated. Metabolism of renzapride by liver microsomes was assessed by
      incubating 10 micromol/L renzapride with human liver microsome samples for 60
      minutes at 37 degrees C. After the reaction was stopped, the samples were
      centrifuged and the supernatant analysed for metabolites by high-pressure liquid
      chromatography (HPLC). The potential inhibitory effects of renzapride on
      cytochrome P450 (CYP) enzymes were assessed by incubating renzapride at various
      concentrations over a 1-500 micromol/L concentration range with microsomes
      genetically engineered to express a single CYP. RESULTS: Renzapride was selective
      for serotonergic receptors and, in particular, had high affinity for human 5
      HT(3) and guinea-pig 5-HT(4) receptors (K(i) 17 and 477 nm, respectively).
      Inhibitory properties at 5-HT(2B) receptors were also identified for renzapride,
      as well as some affinity for 5-HT(2A) and 5-HT(2C) receptors. Renzapride N-oxide
      and its enantiomers demonstrated much lower affinity for all 5-HT receptors
      compared with renzapride. Renzapride was metabolized by liver microsomes to a
      limited extent and there was no significant non-microsomal metabolism of
      renzapride. Renzapride did not inhibit the major CYP drug-metabolizing enzymes
      CYP2C9, CYP2D6, CYP1A2, CYP2A6, CYP2C19, CYP2E1 or CYP3A4 at concentrations
      consistent with use in a clinical setting. CONCLUSIONS: These results confirm and
      extend earlier studies in animal and human receptors that show renzapride is a
      potent and generally full 5-HT(4) receptor agonist and 5-HT(3) receptor
      antagonist. The results reported in the present study indicate that the
      metabolites of renzapride are minor and are unlikely to contribute to its
      therapeutic profile or lead to interaction of renzapride with other drugs that
      inhibit the major drug-metabolizing enzymes in the liver at therapeutic doses.
      These data contribute to the understanding of the pharmacological actions and
      metabolic fate of renzapride in vivo.

PMID- 18095755
TI  - Coccidioidomycosis and other endemic mycoses in Mexico.
AB  - The endemic mycoses traditionally include coccidioidomycosis, histoplasmosis,
      blastomycosis and paracoccidioidomycosis. Although sporotrichosis and
      chromomycosis are technically not included among the endemic mycoses, they are
      frequently diagnosed in Mexico. Most systemic endemic mycoses are a consequence
      of inhaling the fungi, while subcutaneous mycoses are acquired through the
      inoculation of vegetable matter or soil containing the organism.
      Coccidioidomycosis is caused by Coccidioides spp., a dimorphic pathogenic fungus.
      Approximately 60% of exposures result in asymptomatic infection; in the rest
      there are protean manifestations that range from a benign syndrome also known as
      "Valley Fever" to progressive pulmonary or extrapulmonary disease.
      Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic
      to the Americas. Pulmonary histoplasmosis manifestations are protean, ranging
      from a brief period of malaise to a severe, prolonged illness. The spectrum of
      illness in disseminated histoplasmosis ranges from a chronic, intermittent course
      to an acute and rapidly fatal infection. Paracoccidioidomycosis is a chronic,
      granulomatous systemic disease caused by Paracoccidioides brasiliensis that
      characteristically produces a primary pulmonary infection, often asymptomatic,
      and then disseminates to form ulcerative granulomata of the oral, nasal and
      occasionally the gastrointestinal mucosa. Sporotrichosis, caused by Sporothrix
      schenckii, has diverse clinical manifestations; the most frequent is the
      lymphocutaneous form. Generally, infection results from inoculation of the fungus
      through thorns, splinters, scratches and small traumas. Chromomycosis
      (Chromoblastomycosis) is a slowly progressive cutaneous and subcutaneous mycosis
      attributed to various saprophyte Hypomycetes fungi. The primary lesion is also
      thought to develop as a result of percutaneous traumatic inoculation.

PMID- 18095756
TI  - [Cordyceps sinensis, a fungi used in the Chinese traditional medicine].
AB  - Cordyceps sinensis (Berk.) Sacc. is an ascomycete fungus known in China since
      antiquity, which is still being used today. A summary, showing relevant papers
      about this fungus, regarding habitat, history, marketing, consumption,
      nomenclature, pharmacological composition, culture and medical use, is presented.

PMID- 18095757
TI  - [Candida albicans outbreak in a neonatal intensive care unit].
AB  - The appearance of Candida albicans in three patients made physicians investigate
      an outbreak. Outbreak description and microbiologic screening: Case 1 developed
      C. albicans in the placenta culture and in the blood culture carried out on the
      8th day of birth. Four days after this candidemia, C. albicans was recovered in a
      catheter tip of a second neonate (case 2) and finally five days later other
      newborn (case 3) developed C. albicans in the hemoculture. After that, the hands
      of all caregivers as well as case 3's incubator, case 1's mother, and from all
      nine neonates in the unit were studied with swabs. A wet mount was done to all
      swabs and then they were cultured in Chromagar Candida and SDA. All C. albicans
      were studied by RAPD. RAPD study showed that C. albicans recovered from placenta
      and blood cultures of case 1, the catheter tip of case 2 and the blood culture of
      case 3, resulted to be identical and these yeasts were related to the C. albicans
      from the mouth of case 1 mother and the mouth of another colonized newborn. C.
      albicans was not found in the others swabs. The isolations of identical C.
      albicans allowed to suppose the horizontal transmission from the case 1, that had
      acquired it congenitally. Not only isolation of unusual Candida species would be
      an alert. Despite patients' personal factors to justify a fungal infection, the
      recovery of C. albicans in a short period of time should warn physicians about
      the possibility of a horizontal transmission.

PMID- 18095758
TI  - [Examination of the genetic variability among biofilm-forming Candida albicans
      clinical isolates].
AB  - Biofilms are microbial communities encased in a self-produced polymeric matrix
      and represent a common mode of microbial growth. Candida albicans is able to
      colonize the surface of catheters, prostheses, and epithelia, forming biofilms
      that are highly resistant to antimicrobial drugs. The objective of this study was
      the genotypic characterization of biofilm-forming C. albicans clinical isolates
      using RAPD (Random Amplified Polymorphic DNA). We have studied 25 clinical
      isolates of C. albicans from oral cavities, blood, skin, nail, stool, oesophagus
      biopsy and vaginal fluids from patients suffering from candidiasis. For each
      strain biofilm formation was analysed by measuring the ability to adhere to and
      grow on polystyrene plastic surfaces using XTT [2,3-bis(2-methoxi-4nitro
      5sulfophenil)-2H tetrazolium-5carboxanilide] reduction assay. The similarity
      coefficients generated by RAPD using four different primers varied from 49 to
      91%, indicating a high degree of genetic variability between the clinical
      isolates. The dendrogram clustered the isolates in four related groups, all
      groups included strains with very different abilities to form biofilms. The
      isolates with similar genotypes often showed very different biofilm formation
      abilities. Strains were grouped into clusters independently of their clinical
      sources. Our results suggested that a direct correlation does not exist between
      the biofilm-forming ability of natural populations of C. albicans and the
      genotype as determined by RAPD.

PMID- 18095759
TI  - [In vitro activity of amphotericin B and anidulafungin against Candida spp.
      biofilms].
AB  - Invasive infections caused by Candida spp. are increasing worldwide and are
      becoming an important cause of morbidity and mortality in immunocompromised
      patients. A large number of manifestations of candidiasis are associated with the
      formation of biofilms on inert or biological surfaces. Candida spp. biofilms are
      recalcitrant to treatment with conventional antifungal therapies. The aim of this
      study was dual 1) to determine the prevalence of biofilm producers among clinical
      isolates from catheter (16 C. albicans ) and blood culture (2 C. albicans and 30
      C. tropicalis), and 2) to determine the activity of amphotericin B and
      anidulafungin against C. albicans and C. tropicalis biofilms of 24 and 48 hours
      of maturation. Biofilms were developed using a 96-well microtitre plate model and
      production and activity of antifungal agents against biofilms were determined by
      the tetrazolium (XTT) reduction assay. Of catheter and blood isolates, 62.5 and
      56.25%, respectively, produced biofilms. By species, 68.42% of C. albicans and
      53.33% of C. tropicalis were biofilm producers. C. albicans biofilms showed more
      resistance to amphotericin B and anidulafungin than their planktonic
      counterparts. Complete killing of biofilms was never achieved, even at the
      highest concentrations of the drugs tested. Anidulafungin displayed more activity
      than amphotericin B against C. albicans biofilms of 24 hours of maturation (GM
      MIC 0.354 vs. 0.686 microg/ml), but against C. tropicalis biofilms amphotericin B
      was more active (GM MIC 11.285 vs. 0.476 microg/ml). In contrast, against
      biofilms with 48 hours maturation, amphotericin B was more active against both
      species.

PMID- 18095760
TI  - [Concordance between phenotypical features and PCR-REA for the identification of
      Malassezia spp].
AB  - The genus Malassezia has been recently revised and nowadays includes 11 species
      that cannot always be differentiated from each other by physiological and
      morphological tests. This study was aimed to evaluate the correlation between a
      molecular method and conventional phenotypic features in the identification of
      Malassezia spp. To achieve this aim, 92 Argentinean clinical strains isolated
      between 2001 and 2005 were analyzed along with three reference strains
      (Malassezia furfur CBS 7019, Malassezia sympodialis CBS 7222 and Malassezia
      slooffiae CBS 7956). By using PCR and restriction enzyme analysis with three
      different DNA endonucleases (PCR-REA), the molecular method consistently
      identified all three reference strains and all 92 clinical isolates as follows:
      63 M. sympodialis, 18 M. furfur, 10 Malassezia globosa and one Malassezia obtusa.
      Phenotypic studies undentified 85 clinical isolates and two of the reference
      strains (total agreement > 91%). In particular for M. sympodialis, M. furfur and
      M. globosa, the species more frequently involved in human pathology, the
      agreement ranged between 84 and 96%. This result suggests that phenotypic studies
      are suitable for the presumptive identification of important Malassezia species
      in the clinical medical mycology laboratories where molecular methodologies are
      not available.

PMID- 18095761
TI  - [Effectiveness of imazalil to control the effect of fungal deterioration on
      mummies at the Mexico City Museum "El Carmen"].
AB  - We present a study on the control and elimination of the fungi affecting the
      mummies specifically at the museum "El Carmen", in San Angel, Mexico City. Twelve
      analysed mummies presented an important deterioration attributed to colonizing
      fungi. The degree of fungal contamination and the efficacy of imazalil were
      evaluated. Two samplings were performed in order to isolate and identify the
      fungal genera, one for control and the other after the treatment. Isolation was
      done by the carpet-square technique and identification was performed by
      morphological features. Each sampling gave a total of 100 samples as follows: 17
      from the air, 23 from the walls and 60 from the mummies. Samples were cultured on
      Sabouraud dextrose agar. From the first sampling a total of 649 colonies
      corresponding to 24 genera were obtained being the most frequent Penicillium,
      Cladophialophora and Aspergillus. From the second sampling, after the imazalil
      treatment, which was applied by means of lit candles containing the antifungal
      drug, 57 colonies were recovered, representing a 91.2% fungal reduction; 18
      genera were eliminated. In spite of resistance showed by many Penicillium
      strains, the imazalil is an alternative drug for the control of fungal
      colonization on these studied materials.

PMID- 18095762
TI  - The isoepoxydon dehydrogenase gene PCR profile is useful in fungal taxonomy.
AB  - This study evaluates the specificity of PCR isoepoxydon dehydrogenase (idh)
      primers on fungi associated with patulin production. The DNAs of 93 strains were
      extracted and analysed by PCR using primers of the idh gene of patulin
      biosynthesis. A single band at 620 bp was obtained on 17% of the analysed
      strains. Different molecular weight amplicons were observed in other strains.
      These were employed as binary characters for numerical analysis to obtain a
      dendrogram. Clusters were observed, which corresponded to morphological
      identifications in some cases. Amplicons at 400 and/or 500 bp were related to
      patulin non-detection for strains, whereas a 450 bp amplicon was associated with
      some Aspergillus and both of the Byssochlamys nivea strains tested. Hence, the
      idh primers are not specific for the gene and provide other amplicon products in
      other species. These results were useful providing (a) profiles of DNA to
      identify and classify fungi and (b) insights into patulin production. The DNA
      profiles in this study may be useful for the potential of patulin producing
      fungi. Obtaining multiple bands in culture-independent PCR of environmental
      samples by using the primers could indicate that more than one species is
      present.

PMID- 18095763
TI  - [Stereum hirsutum (Wild) Pers. action in dye degradation].
AB  - Stereum hirsutum, a white rot fungus, has a good growth in solid state
      fermentation. This was carried on with wheat bran, soy bran and a mixture of
      both. Mycelia grown on soy bran showed the highest decolorization activity on
      Ponceau 2R (xylidine), indigo carmine and malachite green. Optimal relationship
      between decolorization and detoxification of malachite green was 30 g of fresh
      weight (mycelia plus substrate) in 500 ml malachite green solution, 42 U/l of
      laccase was measured in this solution. Decolorization was carried on without the
      addition either of nutrients or mediators. Conditions for maximal decolorization
      did not agree with those for maximal ligninolytic enzyme production, but
      effectiveness of laccase activity on decolorization was evidenced by
      electrophoretic analysis, that allowed laccase identification and its
      decolorization activity in gels stained with indigo carmine and malachite green,
      with ABTS as mediator. Detoxification was assayed using the sensible fungus
      Phanerochaete chrysosporium.

PMID- 18095764
TI  - Mycobiota of the date palm phylloplane: description and interactions.
AB  - We have analysed the mycobiota of date palm (Phoenix dactylifera, L.) leaves
      using several techniques. Profusely sporulating fungi (Penicillium spp. and
      Cladosporium spp.) developed when plating leaf fragments and leaf washings.
      Fusarium oxysporum, was particularly abundant in leaves infested with the red
      scale insect Phoenicococcus marlatti Cockerell, 1899, but an undescribed
      Lecanicillium cf. psalliotae was also found. Dual and overlay cultures showed
      interactions between palm pathogens, entomopathogenic and saprotrophic fungi. The
      most significant was the strong inhibition of the palm pathogen Penicillium
      vermoesenii caused by the entomopathogen Beauveria bassiana. No symptoms
      developed when F. oxysporum isolated from scale insects or the entomopathogens B.
      bassiana or Lecanicillium dimorphum were wound-inoculated on P. dactylifera
      petioles.

PMID- 18095765
TI  - [Identification and susceptibility against fluconazole and albaconazole of 100
      yeasts' strains isolated from vaginal discharge].
AB  - Vulvovaginal candidiasis is a condition that affects a great number of fertile
      women. It is considered the second cause of genital infection after vaginosis due
      to GAM complex. Candida albicans is the most frequent isolated species from
      vaginal discharge. However, sometimes more than one yeast species could be found
      in the same clinical sample that are more resistant to antifungal drugs.
      Nowadays, it is necessary to identify properly up to species level the isolated
      microorganism and to determine the antifungal susceptibility profile. One hundred
      strains obtained from vaginal discharge of 94 patients suffering acute
      vulvovaginal candidiasis were studied. The identification of the isolates showed:
      C. albicans 86%, Candida glabrata 6%, Candida inconspicua 3%, Candida krusei 2%
      and Candida intermedia, Candida holmii and Trichosporon asahii one case each.
      Minimal inhibitory concentrations (MIC) of all the yeasts against fluconazole and
      albaconazole were performed. C. glabrata, C. krusei and C. inconspicua were the
      most resistant against fluconazole, on the other hand albicans was susceptible to
      this drug. All the isolates presented MIC against albaconazole much lower than
      fluconazole.

PMID- 18095766
TI  - Additive action of honey and starch against Candida albicans and Aspergillus
      niger.
AB  - A comparative method of adding honey to culture media with and without starch was
      used to evaluate the action of starch on the antifungal activity of honey. The
      minimum inhibitory concentration (MIC) expressed in % (v/v) for two varieties of
      honey without starch against Candida albicans was 42% and 46%, respectively. For
      Aspergillus niger the MIC without starch was 51% and 59%, respectively. When
      starch was incubated with honey and then added to media the MIC for C. albicans
      was 28% and 38%, respectively, with a starch concentration of 3.6% whereas the
      MIC for A. niger was 40% and 45%, with a starch concentration of 5.6% and 5.1%
      respectively. This study suggests that the amylase present in honey increases the
      osmotic effect in the media by increasing the amount of sugars and consequently
      increasing the antifungal activity.

PMID- 18095767
TI  - Disseminated histoplasmosis with hemophagocytic syndrome in a patient with AIDS:
      description of one case and review of the Spanish literature.
AB  - We report a case of disseminated histoplasmosis in a 33-year old Ecuadorian
      patient with AIDS and a CD4 lymphocyte count of 39 cells/microl. He presented
      with prolonged fever and cough, was diagnosed with hemophagocytic syndrome and
      multiple organ failure and died 18 days after admission. Histoplasma capsulatum
      was isolated post-mortem from bone marrow biopsy and blood culture. In a
      literature review we found 22 published cases of disseminated histoplasmosis in
      patients with AIDS in Spain since 1988. All but two were men under 50 years old.
      Nineteen had been born or had lived in endemic areas. The diagnosis of
      histoplasmosis was established by culture of bone marrow biopsy in 10 cases.
      Itraconazole was introduced as a second drug after amphotericin B in ten of the
      thirteen patients who survived.

PMID- 18095768
TI  - [Isolation of Sporothrix schenckii from environmental samples in Venezuela].
AB  - The dimorphic fungus Sporothrix schenckii is the etiological agent of
      sporotrichosis, a subcutaneous mycosis frequently found in Latin America. The
      isolation of this fungus from the environment and other sources has been widely
      reported. Nevertheless, to our knowledge this fungus has not been isolated from
      the endemic areas of Venezuela. In studies related to a clinical case of
      sporotrichosis in "Colonia Tovar", produced by traumatism after manipulating soil
      samples, the fungus was isolated from the soil of that particular area. This is
      the first report of the isolation of S. schenckii from environmental sources in
      an endemic area of Venezuela.

PMID- 18095769
TI  - [Resistance to azolic compounds in clinical Trichophyton spp. strains].
AB  - The increase of dermathophytosis in patients with poor therapeutic response leads
      us to study the antifungal susceptibility of 36 clinical isolates to
      itraconazole, ketoconazole and fluconazole by the E-test method. According to
      established parameters by the Clinical Laboratory Standards Institute, the
      resistance to one or more antifungal drugs was demonstrated in seven isolates
      (19.4%) as follows: three Trichophyton rubrum, three T. mentagrophytes and one T.
      tonsurans. A T. rubrum isolate was resistant to the three azolic drugs; the other
      six only to fluconazole. It is important to establish the antifungal
      susceptibility as part of the study procedures in patients with dermatophytosis
      and a poor antifungal response.

PMID- 18095770
TI  - Histological analyses of the fungal endophytes in Rosa hybrida.
AB  - Endophytes are fungi that cause asymptomatic infections in leaves and stems of
      healthy plants. This study evaluated the presence of endophytic fungi on leaves
      of Rosa hybrida collected in Bogota, (Colombia) using histological techniques and
      light microscopy. Histological preparations showed fungal mycelium with few cells
      in the vascular tissue. Colonization of mesophyll cells was not observed.
      Visualization of fungal cells within plant tissues is a confirmatory test of the
      endophytic habitat of fungi isolated from leaves of Rosa hybrida.

PMID- 18095771
TI  - [Clinical cases in Medical Mycology. Case No. 28].

PMID- 18095772
TI  - [Clinical cases in Medical Mycology. Case No. 29].

PMID- 18095773
TI  - [Clinical cases in Medical Mycology. Case No. 30].

PMID- 18095776
TI  - Overview of prevention and treatment of atherosclerosis with lipid-altering
      therapy for pharmacy directors.
AB  - Cardiovascular (CV) disease is the leading cause of mortality and one of the
      leading causes of disability worldwide. Its economic burden is enormous, and the
      estimated direct and indirect costs of the disease in 2006 exceeded $400 billion.
      Low-density lipoprotein cholesterol is recognized as a major cause of coronary
      heart disease and other clinical forms of atherosclerotic disease, and an
      elevated low-density lipoprotein cholesterol level remains the primary target of
      lipid-lowering therapy. Recent retrospective evidence points to deficiencies in
      the management of patients with atherosclerosis in the clinical practice setting.
      Enhancing awareness of the need to monitor and treat dyslipidemia in
      atherosclerosis, and of the benefits of such treatment reported in recent
      studies, may help to narrow this treatment gap. This review will examine the
      development of atherosclerosis and the role atherosclerosis plays in the
      underlying pathophysiology of CV disease. Imaging methods for assessing
      progression of atherosclerosis and new recommendations for risk-reduction therapy
      in patients with established atherosclerotic vascular disease are discussed.
      Emphasis is on newer data regarding the effect of statins in retarding
      progression of atherosclerosis or even inducing regression of atherosclerosis.

PMID- 18095777
TI  - Comparison of low-density lipoprotein cholesterol reduction after switching
      patients on other statins to rosuvastatin or simvastatin in a real-world clinical
      practice setting.
AB  - OBJECTIVE: The study compared low-density lipoprotein cholesterol (LDL-C)
      reduction obtained after switching patients on a statin therapy to rosuvastatin
      or simvastatin in real-world clinical practice. METHODS: Using information from
      an electronic medical records database, for patients >or=18 years of age who
      received newly prescribed statin therapy during August 2003 to March 2006, who
      were switched to either rosuvastatin or simvastatin, and who had LDL-C values at
      baseline, switch and postswitch data were included (N = 277). Percent LDL-C
      reduction between patients switched to rosuvastatin (n = 155) and those switched
      to simvastatin (n = 122) were compared. Linear regression model was adjusted for
      percent LDL-C change from preswitch to switch, LDL-C at time of switch, age, sex,
      smoking, statin aggressiveness, and therapy duration postswitch. Percent LDL-C
      reduction for patients switched from atorvastatin to rosuvastatin versus
      atorvastatin to simvastatin was also compared. RESULTS: Patients switched to
      rosuvastatin or simvastatin were similar in age, sex, and baseline LDL-C (mean,
      146 mg/dL). Patients switched to rosuvastatin from any other statin had a
      significantly greater percent LDL-C reduction (18.4%) postswitch than patients
      switched to simvastatin (5.8%; P = .0003). After adjusting for baseline
      covariates, rosuvastatin patients had a significantly greater percent LDL-C
      reduction postswitch than simvastatin patients (16.0% vs 8.8%, respectively; P =
      .0002). In the subgroup of patients switched from atorvastatin, patients switched
      to rosuvastatin (n = 67) had a significantly greater adjusted percent LDL-C
      reduction (13.6%) postswitch than patients switched to simvastatin (5.5%; n = 75;
      P = .001). CONCLUSION: Rosuvastatin achieves greater percent LDL-C reduction than
      simvastatin as a switch therapy in a real-world clinical practice setting. This
      highlights the need to select the statin to switch to based on additional needed
      percent LDL-C reduction to meet individual patient targets. Availability of
      simvastatin (generic statin) and rosuvastatin (branded statin) as treatment
      options would facilitate efficient and effective management of patients with
      dyslipidemia.

PMID- 18095778
TI  - Understanding practice patterns and low-density lipoprotein cholesterol goal
      attainment implications of switching patients from simvastatin in a health plan
      setting.
AB  - OBJECTIVE: To understand the practice patterns and National Cholesterol Education
      Panel (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol
      (LDL-C) goal attainment rates after switching patients from simvastatin (SMV) to
      other statins or the combination of SMV and ezetimibe (EZE). METHODS: This
      retrospective study linked claims and laboratory data from a national health
      plan. Patients were included if they were taking SMV and were switched to other
      statins or a fixed-dose combination of SMV and EZE between July 1, 2005, and June
      30, 2006. Patients taking dual SMV/EZE before switch were excluded from the
      study. The NCEP ATP III risk status of patients at switch was assessed based on
      medical claims, pharmacy claims, and laboratory values in the 12-month preswitch
      period. Lipid data (available on a patient subset) were used to estimate
      patients' goal attainment status at and after switch. RESULTS: Of 134 168
      patients taking SMV, 11 929 (8.9%) switched to other statins or SMV/EZE. The mean
      age of switching patients was 54 years (standard deviation, 9 years), 61% were
      men, 50% were high risk, and 30% were moderate risk. The mean time to switch
      among new starters of SMV (n = 3379) was 77 days. Forty percent (n = 4772) of the
      total switches occurred among those taking the lower doses (5, 10, and 20 mg) of
      SMV. Most patients switched from SMV to SMV/EZE (60.5%), followed by atorvastatin
      (17.3%), rosuvastatin (10.1%), lovastatin (8.6%), pravastatin (2.9%), and
      fluvastatin (0.7%). Similarly, most patients switching from higher doses of SMV
      switched to SMV/EZE (52.5%), followed by atorrestatin (21.1%) and rosuvastatin
      (10.1%). Overall, 55.6% (758 of 1362) of patients were at ATP III goal at the
      time of switch from SMV (across all doses; n = 758), and 56.1% (292 of 521) of
      those taking lower doses were at goal at time of switch. A majority (69.9%) of
      patients who were at goal and switched from SMV (across all doses) were switched
      to SMV/EZE, and 61.6% of those at lower doses of SMV switched to the combination
      drug. Of patients who were not at goal at switch (n = 604), 73.3% attained ATP
      III LDL-C goal after switch. The mean percent LDL-C reduction that was needed to
      attain LDL-C goal at switch from SMV (n = 604) was 18.1%. CONCLUSIONS: There is
      an opportunity to further increase LDL-C goal attainment rates among patients
      switched from SMV. The clinical, prescription benefit design, and economic
      implications of the finding that a majority of patients are at goal when switched
      from SMV and a majority of patients are being switched from SMV to SMV/EZE need
      to be further examined.

PMID- 18095779
TI  - An integrated approach: bisphosphonate management for the treatment of
      osteoporosis.
AB  - Osteoporosis is underrecognized and undertreated despite the availability of
      effective therapies that reduce fracture risks. Bisphosphonates are currently the
      most widely prescribed pharmacologic treatment for osteoporosis. Oral
      bisphosphonates are typically managed under the pharmacy benefit of a health
      plan. With the recent availability of intravenous bisphosphonates, osteoporosis
      therapies now cross both the traditional pharmacy and medical benefit boundaries.
      Determining the most appropriate and cost-effective treatment for specific
      populations requires best practices that integrate both pharmacy and medical
      benefit considerations. When developing policy as part of these best practices,
      medical directors and pharmacy directors must consider efficacy, safety, cost,
      convenience, and mode of administration for each of the bisphosphonate
      formulations. This continuing education activity, based on a roundtable of
      managed care experts, explores new approaches for developing an effective
      bisphosphonate management policy for the treatment of osteoporosis.

PMID- 18095780
TI  - Into the light: strategies for battling hepatitis C.
AB  - The primary measurable goal of hepatitis C virus (HCV) therapy is permanent
      eradication of the virus (ie, a sustained virologic response [SVR]). Treatment
      decisions depend on the severity and treat ability of the infection,
      contraindications to treatment, and patient preferences. The current standard of
      treatment is combination therapy with pegylated interferon (peginterferon) and
      ribavirin. Dosages and treatment duration vary according to viral genotype. About
      70% to 80% of patients with genotype 2 or 3 will achieve SVR compared with only
      40% to 50% of patients with genotype 1. Generally, those who previously failed
      HCV treatment with monotherapy or standard interferon plus ribavirin should be
      considered for re-treatment with a trial of peginterferon and ribavirin. Side
      effects associated with treatment include influenzalike symptoms, insomnia,
      neutropenia, and hemolytic anemia and should be managed aggressively to promote
      patient adherence to therapy. Future pharmacologic agents are currently in
      development for patients failing treatment or those who have relapsed.

PMID- 18095781
TI  - Making it happen: managed care considerations in vanquishing hepatitis C.
AB  - Chronic hepatitis C virus (HCV) infection is an area of medical and economic
      concern. Studies show a substantial and increasing use of healthcare resources by
      patients with this disease. However, analysis of available data regarding
      virologic efficacy, impact on outcomes, and cost-effectiveness in chronic HCV
      infection appear to justify the initial costs for antiviral treatment,
      considering the future cost savings generated by prevention of liver disease. To
      further demonstrate cost-effectiveness, enhanced methods for identifying and
      treating patients are needed. Greater clinician awareness of available
      guidelines, patient education, close monitoring of antiviral therapy, emphasis on
      adherence to therapy, and management of adverse effects are recommended to ensure
      the best possible care for patients and to maximize outcomes.

PMID- 18095782
TI  - The burden of dementia.
AB  - Dementia care is a significant and growing healthcare need that will have major
      economic and medical impact as the prevalence of Alzheimer's disease (AD) and
      related dementias continues to increase in the United States during the next 50
      years. The ability to differentiate the signs and symptoms of the most common
      dementing illnesses - AD, vascular dementia, frontotemporal dementia, and
      dementia with Lewy bodies - is essential to dementia care and management.
      Additionally, dementia patients in longterm care (LTC) facilities are prone to
      significantly greater risk of negative outcomes compared with nondemented
      residents as a result of a decline in activities of daily living, physical
      capacities, and behavioral manifestations. Careful and active assessment of risk
      factors and their management provides opportunities for improving outcomes. These
      include behavioral manifestations of pain, wandering, and risks of malnutrition,
      falls and injuries, and restraint use. Specific nonpharmacologic interventions to
      promote restraint- and pain-free care in LTC are highlighted.

PMID- 18095783
TI  - Current issues in dementia pharmacotherapy.
AB  - Diagnosis and treatment of dementia in nursing homes and assisted living
      facilities remains challenging since response to treatment and disease course
      varies for the common degenerative dementias. Four cholinesterase inhibitors and
      an N-methyl-D-aspartate glutamate receptor antagonist are approved by the US Food
      and Drug Administration for the treatment of Alzheimer's disease (AD). Treatment
      with AD medications is clinically efficacious and associated with reduced
      caregiver burden. Some controlled trials have reported that cholinesterase
      inhibitors and memantine ameliorate dementia-related behavioral symptoms.
      Antipsychotic therapy is often used for intractable behavioral symptoms or
      psychosis not responding to nonpharmacologic interventions and antidementia
      medications; however, the risk/benefit ratio for each patient should be
      critically evaluated, because treatment with atypical antipsychotics has been
      associated with serious adverse events, including increased risk for death in
      older adults with dementia.

PMID- 18095784
TI  - Current implications for the managed care of dementia.
AB  - Medicare Part D changes are becoming an increasingly complex issue, presenting a
      challenge to many physicians treating dementia patients. A 2006 American Medical
      Directors Association survey found that 70% of its members reported difficulty
      with the Medicare prescription drug plan, with 28% of all physicians having
      difficulty in accessing dementia medications. Concerns about medication access
      are worrisome, particularly in light of data demonstrating their positive effects
      on behavioral symptoms, which may result in reduced use of psychotropic
      medications. Strategies for improving access to antidementia medications in
      nursing homes and assisted living facilities are highlighted, including an
      overview of appropriate use of antidementia medications (cholinesterase
      inhibitors and glutamate pathway modifiers), use of nonpharmacologic
      interventions, risk reduction in patients with dementia, accounting for resident
      preferences, and proper documentation. Finally, end-of-life issues in advanced
      dementia and defining quality of life are also addressed in a brief commentary.
      Recognition and understanding of these issues may improve patient access to
      medication, leading to improved patient healthcare outcomes and reduced dementia
      related healthcare costs.

PMID- 18095785
TI  - Health-related quality of life--an introduction.
AB  - Chronic diseases often have a relapsing and remitting course with substantial
      impact on function and quality of life. Rheumatoid arthritis (RA) is considered a
      chronic, inflammatory autoimmune disorder that causes disabling and painful
      inflammation in the joints that can lead to detrimental effects on health-related
      quality of life (HRQOL). This article provides an overview of HRQOL and a
      comprehensive description of the attributes of different instruments to measure
      it. A wide variety of instruments have been created to measure HRQOL using 2
      approaches: health status and health utility. Commonly used generic health status
      instruments in RA are the Medical Outcomes Study 36-Item Short Form (SF-36) and
      the Health Assessment Questionnaire Disability Index. Health utility measures are
      divided into 2 categories, direct and indirect. The most common direct health
      utility measures are the standard gamble, time to trade-off, and rating scale,
      while the most commonly used indirect measures are EuroQOL, SF-6D, and the Health
      Utility Index. Different applications of the instruments are analyzed in this
      article, including their utility to estimate burden of disease, as end points in
      clinical trials, and to monitor outcomes in clinical practice, as well as their
      uses in public policy and in individual decision making.

PMID- 18095786
TI  - Generic quality-of-life assessment in rheumatoid arthritis.
AB  - BACKGROUND: Generic health status measures are commonly used in the evaluation of
      rheumatoid arthritis (RA) patients. The reliability, validity, and sensitivity of
      the instruments in the assessment of quality of life (QOL) in RA, and how they
      correlate to other clinical measurements, have long been questioned. OBJECTIVE:
      Analyze the performance of a commonly used generic health status measure, the
      Medical Outcomes Study 36-Item Short Form (SF-36), against the Outcome Measures
      in Rheumatology (OMERACT) criteria. METHODS: Data were analyzed from 7 double
      blind, randomized controlled trials that examined the effectiveness of 1 or more
      interventions in RA. The primary outcome measures evaluated were the Mental and
      Physical Component Scores of the SF-36. Comparators were 1 or more of the
      following: the Health Assessment Questionnaire scores, tender joint count (TJC),
      the Disease Activity Score, and the American College of Rheumatology Responder
      Index (ACR20, ACR50, ACR70). The ability to detect a treatment effect in the
      study outcomes was evaluated using 3 measures: treatment difference, standardized
      response mean, and relative efficiency in relation to the TJC. RESULTS: As a
      generic QOL measure, the SF-36 is better suited to capture the holistic health of
      the patient, as reflected in the World Health Organization definition of health
      as being not only the avoidance of disease but the physical, emotional, and
      social well-being of the patient. Furthermore, use of the SF-36 permits
      comparisons of physical and mental aspects of QOL in the RA patient population,
      as well as comparisons of QOL parameters between patients with RA, other patient
      groups, and the general population. CONCLUSION: The SF-36 deserves serious
      consideration for inclusion in the core set of outcomes in RA trials.

PMID- 18095787
TI  - Improved health-related quality of life with effective disease-modifying
      antirheumatic drugs: evidence from randomized controlled trials.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by
      inflammation of the articular synovium, resulting in bony erosions, deformity,
      and, ultimately, joint destruction. With associated comorbid conditions,
      especially cardiovascular, it can result in significant morbidity as well as
      early mortality. Patients with RA report impairments in health-related quality of
      life (HRQOL) in comparison with age- and sex-matched populations without
      arthritis. These decreases in HRQOL are attributed to the pain, impairment in
      physical function, and fatigue associated with this disease. The introduction of
      new disease-modifying antirheumatic drugs has revolutionized the treatment of RA,
      particularly the biologic agents: etanercept, infliximab, adalimumab, abatacept,
      and rituximab. Importantly, administration of these agents has resulted in
      statistically significant and clinically meaningful improvements in physical
      function and HRQOL. Many clinical studies confirm that with these therapies, RA
      patients report improvements in HRQOL, reflected by improved physical function,
      less fatigue, and better emotional and mental function. Maintenance of physical
      function is no longer the only treatment goal for RA but also to improve,
      restore, and preserve HRQOL. Results from pivotal clinical trials are analyzed in
      this article and the relevance of the data derived from the clinical studies to
      day-to-day clinical practice are also discussed.

PMID- 18095788
TI  - The future of outcomes measurement in rheumatology.
AB  - Quality-of-life (QOL) measurement has a rich history in rheumatology, and
      although the study of health measurements has expanded remarkably in recent
      years, there are a number of methodological issues that need attention. This
      article focuses on utility-based measures that are most relevant to public policy
      and some major issues that remain unresolved. The duration of a health condition,
      for example, is a central component of health outcome. However, the majority of
      measures currently used in rheumatology do not consider the duration of condition
      or the long-term consequences of disease or treatment. Similarly, there are many
      levels at which preference is expressed in the healthcare decision process, and
      despite a wealth of literature on QOL measurement, we still have much more to
      learn about how to present information to patients and how to use preference data
      that patients provide. Improvements in the utility assessment method are urgently
      needed as well, as different utility-based measures such as standard gamble, time
      trade-off, and rating scales are not comparable. This lack of comparability has
      important implications when estimating quality-adjusted life-years in cost
      utility studies. Another key unresolved issue is whether the Medical Outcomes
      Study 36-Item Short Form and the Health Assessment Questionnaire offer
      appropriate data for cost-utility studies. The current estimation of clinical
      benefit is also controversial, as competing measurement tools offer different
      estimates of wellness at baseline. However, the different approaches yield
      surprisingly similar estimates of change. Clearly, this observation deserves
      further study and replication in future studies.

PMID- 18095790
TI  - Using neuroimaging to resolve the psi debate.
AB  - Abstract Parapsychology is the scientific investigation of apparently paranormal
      mental phenomena (such as telepathy, i.e., "mind reading"), also known as psi.
      Despite widespread public belief in such phenomena and over 75 years of
      experimentation, there is no compelling evidence that psi exists. In the present
      study, functional magnetic resonance imaging (fMRI) was used in an effort to
      document the existence of psi. If psi exists, it occurs in the brain, and hence,
      assessing the brain directly should be more sensitive than using indirect
      behavioral methods (as have been used previously). To increase sensitivity, this
      experiment was designed to produce positive results if telepathy, clairvoyance
      (i.e., direct sensing of remote events), or precognition (i.e., knowing future
      events) exist. Moreover, the study included biologically or emotionally related
      participants (e.g., twins) and emotional stimuli in an effort to maximize
      experimental conditions that are purportedly conducive to psi. In spite of these
      characteristics of the study, psi stimuli and non-psi stimuli evoked
      indistinguishable neuronal responses-although differences in stimulus arousal
      values of the same stimuli had the expected effects on patterns of brain
      activation. These findings are the strongest evidence yet obtained against the
      existence of paranormal mental phenomena.

PMID- 18095789
TI  - Dissociable roles of the superior temporal sulcus and the intraparietal sulcus in
      joint attention: a functional magnetic resonance imaging study.
AB  - Abstract Previous imaging work has shown that the superior temporal sulcus (STS)
      region and the intraparietal sulcus (IPS) are specifically activated during the
      passive observation of shifts in eye gaze [Pelphrey, K. A., Singerman, J. D.,
      Allison, T., & McCarthy, G. Brain activation evoked by perception of gaze shifts:
      The influence of context. Neuropsychologia, 41, 156-170, 2003; Hoffman, E. A., &
      Haxby, J. V. Distinct representations of eye gaze and identity in the distributed
      human neural system for face perception. Nature Neuroscience, 3, 80-84, 2000;
      Puce, A., Allison, T., Bentin, S., Gore, J. C., & McCarthy, G. Temporal cortex
      activation in humans viewing eye and mouth movements. Journal of Neuroscience,
      18, 2188-2199, 1998; Wicker, B., Michel, F., Henaff, M. A., & Decety, J. Brain
      regions involved in the perception of gaze: A PET study. Neuroimage, 8, 221-227,
      1998]. Are the same brain regions also involved in extracting gaze direction in
      order to establish joint attention? In an event-related functional magnetic
      resonance imaging experiment, healthy human subjects actively followed the
      directional cue provided by the eyes of another person toward an object in space
      or, in the control condition, used a nondirectional symbolic cue to make an eye
      movement toward an object in space. Our results show that the posterior part of
      the STS region and the cuneus are specifically involved in extracting and using
      detailed directional information from the eyes of another person to redirect
      one's own gaze and establish joint attention. The IPS, on the other hand, seems
      to be involved in encoding spatial direction and mediating shifts of spatial
      attention independent of the type of cue that triggers this process.

PMID- 18095793
TI  - Tonic-clonic seizure as the presentation symptom of severe hypocalcemia secondary
      to zoledronic acid administration.

PMID- 18095794
TI  - Levorphanol revisited.

PMID- 18095795
TI  - Hospitals and hospices partner to extend the continuum of palliative care.

PMID- 18095796
TI  - Death from renal failure eighty years on: how far have we come?

PMID- 18095797
TI  - Language matters: "sometimes we withdraw treatment but we never withdraw care".

PMID- 18095798
TI  - Renal supportive care: view from across the pond: the United States perspective.
AB  - Renal supportive care is an emerging field of study and practice in the United
      States. Data from the United States Renal Data System (USRDS) have informed us of
      the poor prognosis for many dialysis patients, the incidence of dialysis
      withdrawal, and the underutilization of hospice services. Practice guidelines,
      research in the field, and the available resources are discussed.

PMID- 18095799
TI  - Maximum conservative management: a worthwhile treatment for elderly patients with
      renal failure who choose not to undergo dialysis.
AB  - This paper has been compiled from a presentation given by the first author to the
      "Palliative and End of Life Care in Chronic Kidney Disease: The Evidence" meeting
      held in London in October 2006. It summarizes some of what is known about the
      topic as well as the authors' research and experience in the field.

PMID- 18095800
TI  - Epidemiology of renal palliative care.
AB  - The need for palliative care for patients with end-stage renal disease (ESRD) is
      increasingly recognized. Patients starting renal replacement therapy are now
      elderly, with a median age of 65 years, and with multiple comorbid conditions.
      Quality of life is often poor and with advance care planning, patients can be
      enabled to make the choice of stopping or not starting dialysis. With planned end
      of-life management patients can then choose their place of death. These
      discussions have to be initiated by the renal team. The involvement of palliative
      care professionals in patients with ESRD is therefore both educational and the
      provision of community and hospice care.

PMID- 18095801
TI  - Opioid serum concentrations in patients with chronic pain.
AB  - One hundred fifty-eight opioid serum concentrations from 110 chronic pain
      patients who were prescribed opioids reveal that patients with chronic pain may
      be quite functional and tolerant to high opioid dosages. Opioid serum
      concentrations must only be interpreted in light of whether the blood sample was
      taken from a nontolerant person or a chronic pain patient who has taken opioids
      over a long time period.

PMID- 18095802
TI  - Wrap your worthy cause in a corporate image.

PMID- 18095803
TI  - A palliative care career.

PMID- 18095804
TI  - A psychiatric perspective of dialysis discontinuation.
AB  - In the 1970s, the suicide rate of patients with end-stage renal disease (ESRD)
      was calculated by conflating deaths from obvious clinical suicide attempts with
      deaths caused by lethal noncompliance and deaths preceded by dialysis
      discontinuation. Three decades later, although society's view about cessation of
      life-support treatment has markedly changed, relatively little is known about the
      psychiatric aspects of dialysis discontinuation. This paper reviews the
      literature and suggests a number of findings that warrant further research
      investigation.

PMID- 18095805
TI  - Symptoms in advanced renal disease: a cross-sectional survey of symptom
      prevalence in stage 5 chronic kidney disease managed without dialysis.
AB  - BACKGROUND: Numbers of patients with stage 5 chronic kidney disease (CKD) managed
      conservatively (without dialysis) are increasing steadily but prevalence and
      severity of symptoms in this population are not yet known. AIM: To describe
      symptom prevalence, symptom severity, and total symptom burden in patients with
      stage 5 CKD managed conservatively. METHOD: A cross-sectional survey of patients
      with stage 5 CKD managed conservatively, in three U.K. renal units. Symptoms were
      assessed using the patient-completed Memorial Symptom Assessment Scale Short Form
      (MSAS-SF), with additional renal symptoms. RESULTS: Sixty-six patients were
      recruited (response rate, 62%), with mean age 82 years (standard deviation [SD]
      +/- 6.6), and mean estimated glomerular filtration rate 11.2 mL/min (SD +/- 2.8).
      Symptoms reported by more than one third or 33% of patients were (95% confidence
      intervals shown in parentheses): lack of energy, 76% (66%-84%); pruritus, 74%
      (65%-82%); drowsiness, 65% (54%-74%); dyspnea, 61% (50%-70%); edema, 58% (47%
      66%); pain, 53% (42%-63%); dry mouth, 50% (39%-60%); muscle cramps, 50% (39%
      60%); restless legs, 48% (38%-58%); lack of appetite, 47% (37%-58%); poor
      concentration, 44% (34%-54%); dry skin, 42% (32%-53%); sleep disturbance, 41%
      (32%-51%); and constipation, 35% (26%-45%). Mean number of symptoms reported on
      MSAS-SF was 11.58 (SD +/- 5.2), with an additional 2.77 (SD +/- 1.7) renal
      symptoms. Symptoms were also most severe in the more prevalent symptoms. Pain was
      an exception, with disproportionately greater severity (32% of all patients
      reported moderate/severe pain). CONCLUSION: This study demonstrates that patients
      with stage 5 CKD have considerable symptom control needs, similar to advanced
      cancer populations, but with different patterns of individual symptoms and
      severity, particularly pain. Implications for palliative care, hospice, and
      nephrology services in planning and providing care are discussed.

PMID- 18095806
TI  - The prevalence and management of chronic pain in end-stage renal disease.
AB  - A growing body of literature has demonstrated that chronic pain is common for
      patients with end- stage renal disease (ESRD), is typically moderate or severe,
      and impacts virtually every aspect of health-related quality of life.
      Unfortunately, there is a lack of clinical and research focus in this area in
      nephrology and pain in ESRD is undertreated. This paper reviews the epidemiology
      of chronic pain in ESRD, discusses basic principles of pain assessment and
      management, and highlights some of the challenges in pain management in ESRD with
      the hope of guiding health professionals in the effective management of pain in
      patients with ESRD.

PMID- 18095807
TI  - Exploring the option of voluntarily stopping eating and drinking within the
      context of a suffering patient's request for a hastened death.
AB  - There is an acknowledged difficulty in distinguishing between some morally and
      legally accepted acts that hasten dying, such as refusing life-sustaining
      treatment, and other acts that also hasten dying that are labeled as acts of
      "suicide." Recent empirical findings suggest that most terminally ill and
      suffering patients who voluntarily chose to stop eating and drinking as a means
      to hasten their dying generally experienced a "good" death. This paper explores
      the moral and legal status of a decision to stop eating and drinking as a means
      to hasten dying that is voluntarily chosen by a competent, terminally ill and
      suffering patient. The option of voluntarily forgoing food and fluid will be
      compared to other end-of-life clinical practices known to hasten dying, with
      emphasis on the issue of whether such practices can or should be distinguished
      from suicide.

PMID- 18095808
TI  - Physicians' influence over decisions to forego life support.
AB  - OBJECTIVE: To quantify the association between individual physicians and
      decisions to limit use of life supporting therapies for critically ill patients.
      STUDY DESIGN: Prospective, observational data collected 2002-2005 in the adult
      medical intensive care unit (ICU) of a publicly owned teaching hospital. Nine
      intensivists staff this closed-model ICU; in rotating 2 week blocks of time one
      intensivist is responsible for directing all care. In order to uniquely associate
      care with individual physicians, eligible patients were cared for by a single
      intensivist throughout their ICU stay. Life support decisions were identified as
      orders to withhold or withdraw any form of life supporting medical therapy,
      including cardiopulmonary resuscitation (CPR), defibrillation, invasive
      mechanical ventilation, vasoactive drugs, and renal replacement therapy. We used
      multivariable Cox modeling to identify variables associated with decisions to
      limit use of life support. The association with the individual physicians was
      assessed as the hazard ratios of indicator variables representing the individual
      physicians. RESULTS: A decision to limit use of life support was made in 191
      (14.0%) of 1363 ICU admissions. The hazard ratios associated with individual
      intensivists spanned a 15-fold range (0.069-1.042; p = 0.0003). Decisions to
      limit life support were more strongly related to the identity of the intensivist
      than to comorbid conditions, acute diagnostic category, and the source of ICU
      admission. CONCLUSIONS: We have, for the first time, quantified the association
      between individual physicians and decisions made to limit life support for
      critically ill patients. More research is needed to understand the nature and
      implications of this association.

PMID- 18095809
TI  - Stability studies of binary mixtures of haloperidol and/or midazolam with other
      drugs for parenteral administration.
AB  - BACKGROUND: Haloperidol and or midazolam are frequently combined with other drugs
      in the same solution and infused parenterally over several days to treat
      symptoms. The solutions may be delivered to the home well in advance of the time
      of administration. Consequently, physiochemical stability of these combinations
      needs to be studied. OBJECTIVE: Determine the stability and physical
      compatibility of binary mixtures of haloperidol with morphine, scopolamine and
      midazolam and binary mixtures of midazolam with scopolamine and morphine.
      METHODS: Mixtures of drugs were prepared under aseptic conditions in 0.9% sodium
      chloride or 5% glucose at concentrations used clinically for continuous infusion
      and stored in synthetic polyisoprenoid containers at room temperature in the
      presence of light for 15 days. Chemical stability was evaluated by high pressure
      liquid chromatography. Physical compatibility was tested by visual inspection for
      evidence of precipitation and color change. RESULTS: No changes in color,
      precipitation of the components, or measurable losses of volume were noted. The
      majority of the combinations tested were stable for 15 days (T(90) >/= 15 day).
      However, the mixture of haloperidol and morphine reached T(90) at 10 and 9 days.
      The mixture containing haloperidol and scopolamine was stable for only 1 day
      (T(90) </= 1 day). CONCLUSIONS: Common combinations of medications to control
      symptoms are compatible when mixed in 5% glucose or 0.9% sodium chloride.
      However, stability over 15 days is not uniform.

PMID- 18095810
TI  - Assessing the role of human recombinant hyaluronidase in gravity-driven
      subcutaneous hydration: the INFUSE-LR study.
AB  - BACKGROUND: Subcutaneous hydration has potential advantages over intravenous.
      Despite studies supporting the efficacy and safety of subcutaneous hydration it
      has not been studied extensively to date either with or without hyaluronidase.
      OBJECTIVES: To compare flow rate, tolerability, and safety of gravity-driven
      subcutaneous fluid administration with and without recombinant human
      hyaluronidase (rHuPH20) in healthy volunteers. DESIGN: Randomized, double-blind,
      placebo-controlled, within-subject trial. SETTING: Contract research
      organization. PARTICIPANTS: Fifty-four volunteers. INTERVENTION: 24-gauge
      angiocatheters were placed subcutaneously in both upper arms. Each arm received
      rHuPH20 (150 U, 750 U, or 1500 U) or equal volume saline placebo. Immediately,
      400 mL Lactated Ringer's (LR) solution was gravity-infused from a 100 cm height.
      In the pilot stage, 5 subjects also received a similar intravenous infusion.
      MEASUREMENTS: Primary outcome was time to infuse 400 mL LR. Secondary outcomes
      included discomfort assessments, edema, arm circumference, time to recover to
      baseline arm circumference, subject and investigator global preference, and
      adverse events. RESULTS: rHuPH20 150 U, 750 U, and 1500 U yielded mean flow rates
      of 383 +/- 119 mL/hr, 518 +/- 154 mL/hr, and 494 +/- 136 mL/hr, respectively,
      compared to their respective placebo rates of 82 +/- 30 mL/hr, 148 +/- 57 mL/hr,
      and 124 +/- 50 mL/hr. rHuPH20 was well tolerated. CONCLUSIONS: In volunteers,
      clinically relevant fluid volumes can be rapidly delivered subcutaneously with
      rHuPH20 in a well-tolerated manner without a pump. These findings suggest that
      this method of hydration could potentially replace intravenous infusions in many
      clinical settings; further studies with rHuPH20, in patients, are warranted.

PMID- 18095811
TI  - Spirituality and job satisfaction among hospice interdisciplinary team members.
AB  - As a continuing effort to enhance the quality of palliative care for the dying,
      this study examined (1) the prevalence of spirituality among hospice
      interdisciplinary team (IDT) members; (2) whether spirituality is related to job
      satisfaction; and (3) the structural path relationships among four variables:
      spiritual belief, integration of spirituality at work, self actualization and job
      satisfaction. The study surveyed 215 hospice IDT members who completed the Jarel
      Spiritual Well-Being Scale, the Chamiec-Case Spirituality Integration and Job
      Satisfaction Scales. Multiple regression and structural path modeling methods
      were applied to explain the path relationships involving all four variables. The
      IDT members surveyed were: nurses, 46.4%; home health aids, 24.9%; social
      workers, 17.4%; chaplains, 4.2%; physicians, 2.3%; and other, 4.8%. Ninety-eight
      percent of the respondents viewed themselves as having spiritual well-being. On a
      0-100 scale, IDT staff reported high spiritual belief (mean = 89.4) and they were
      self-actualizing (mean = 82.6). Most reported high job satisfaction (mean = 79.3)
      and spiritual integration (mean = 67.9). In multiple regression, spirituality,
      integration and self-actualization explained 22% of the variation in job
      satisfaction (R = 0.48; adjusted R(2) = 0.218; df = 3,175; F = 17.2; p = 0.001).
      Structural path models revealed that job satisfaction is more likely to be
      realized by a model that transforms one's spirituality into processes of
      integrating spirituality at work and self actualization (chi(2) = 0.614; df = 1;
      p = 0.433) than a model that establishes a direct path from spirituality to job
      satisfaction (chi(2) = 1.65; df = 1; p = 0.199). Hospice IDT member's integration
      of their spirituality at work and greater self actualization significantly
      improve job satisfaction.

PMID- 18095812
TI  - Racial differences in the willingness to use hospice services.
AB  - OBJECTIVE: This study assesses whether racial differences exist in the
      willingness to use hospice services in the future among black and white adults
      and potential factors that may contribute to such differences. METHODS: Data were
      collected from the City of Cincinnati component of the Greater Cincinnati Survey.
      A total of 510 random-digit-dialed telephone interviews were completed, with 473
      adults included in the analyses (220 blacks, 253 whites). RESULTS: Relative to
      whites, blacks were significantly less likely to consider using hospice if they
      were near the end of life because of a terminal illness and less likely to do so
      even if their doctor strongly recommended its use. This reluctance was related to
      their prior exposure to hospice as well as their trust in their doctor to make
      the right end-of-life care decisions. Like whites, blacks who had a positive
      prior exposure to hospice were more willing to consider using hospice than those
      who have not been exposed to hospice, but only for those blacks who trust their
      doctor. For blacks who do not trust their doctor, those with prior hospice
      exposure, regardless of their level of satisfaction, were less willing to
      consider hospice than those without prior exposure. CONCLUSIONS: Efforts to
      increase utilization of hospice services among blacks requires greater insight
      into the experiences that they have with hospice services for their family
      members and friends as well as their level of trust in their physician's decision
      making about end-of-life care.

PMID- 18095813
TI  - What should be the optimal cut points for mild, moderate, and severe pain?
AB  - PURPOSE: Grouping patients' rating of pain intensity from 0 to 10 into categories
      of mild, moderate, and severe pain is useful for informing treatment decisions,
      interpreting study outcomes, as well as aiding policy or clinical practice
      guidelines development. In 1995, Serlin and colleagues developed a technique to
      establish the cut points for mild, moderate, and severe pain by grading pain
      intensity with functional interference. Since then, a number of studies attempted
      to confirm these findings in similar or different populations but had different
      results. Such inconsistencies in the literature prompt for more research to
      establish the definition of mild, moderate and severe pain. Thus, the purpose of
      the current study was to identify optimal cut points (CP) of the three pain
      severity categories for worst, average, and current pain. PATIENTS AND METHODS:
      The study population (n = 199) was patients with symptomatic bone metastases
      referred to a palliative radiotherapy clinic. Using the Brief Pain Inventory
      (BPI), patients reported their worst, average, and current pain intensity, as
      well as the degree of functional interference due to pain. All possible
      combinations for the CPs, between 2 and 8, were created and related to the set of
      7 interference items from the BPI using the multivariate analysis of variance
      (MANOVA). The criteria used to determine the optimal set of cut points for mild,
      moderate and severe pain was a MANOVA among pain severity categories that yielded
      the largest F ratio for the between-category effect on the 7 interference items
      as indicated by Pillai's trace, Wilk's lambda, and Hotelling's trace F
      statistics. RESULTS: Results confirmed a non-linear relationship between cancer
      pain severity and functional interference. The optimal CP for worst and average
      pain was CP4, 6 (mild = 1-4, moderate = 5-6, and severe = 7-10), confirming
      Serlin and colleagues's findings. CONCLUSION: These findings are pivotal in
      further understanding the meaning of pain intensity levels and the assessment of
      pain in patients with metastatic cancer. However, further research in alternative
      methods of defining the optimal CP and clinically important change should be
      considered.

PMID- 18095814
TI  - The economic and clinical impact of an inpatient palliative care consultation
      service: a multifaceted approach.
AB  - BACKGROUND: While there has been a rapid increase of inpatient palliative care
      (PC) programs, the financial and clinical benefits have not been well
      established. OBJECTIVE: Determine the effect of an inpatient PC consultation
      service on costs and clinical outcomes. DESIGN: Multifaceted study included: (1)
      interrupted time-series design utilizing mean daily costs preintervention and
      postintervention; (2) matched cohort analysis comparing PC to usual care
      patients; and (3) analysis of symptom control after consultation. SETTING: Large
      private, not-for-profit, academic medical center in San Francisco, California,
      2004-2006. SUBJECTS: Time series analysis included 282 PC patients; matched
      cohorts included 27 PC with 128 usual care patients; clinical outcome analysis of
      48 PC patients. MAIN OUTCOME MEASURE(S): Mean daily patient costs and length of
      stay (LOS); pain, dyspnea, and secretions assessment scores. RESULTS: Mean daily
      costs were reduced 33% (p < 0.01) from preintervention to postintervention
      period. Mean length of stay (LOS) was reduced 30%. Mean daily costs for PC
      patients were 14.5% lower compared to usual care patients (p < 0.01). Pain,
      dyspnea, and secretions scores were reduced by 86%, 64%, and 87%, respectively.
      Over the study period, time to PC referral as well as overall ALOS were reduced
      by 50%. CONCLUSIONS: The large reduction in mean daily costs and LOS resulted in
      an estimated annual savings of $2.2 million in the study hospital. Our results
      extend the evidence base of financial and clinical benefits associated with
      inpatient PC programs. We recommend additional study of best practices for
      identifying patients and providing consultation services, in addition to
      progressive management support and reimbursement policy.

PMID- 18095815
TI  - End-of-life and palliative care education for final-year medical students: a
      comparison of Britain and the United States.
AB  - PURPOSE: (1) To assess British medical students' experiences and education in
      palliative care. (2) To compare experiences and education in palliative care
      between medical students in Britain and the United States. METHOD: Using a self
      administered questionnaire adapted from an earlier U.S. study, British students
      were surveyed on the quantity and quality of palliative care education, training
      in specific end-of-life topics, preparation to provide end-of-life care, exposure
      to palliative care role models, attitudes, and culture. RESULTS: Four hundred
      forty-five final-year students from four British medical schools (response rate
      97% in sampled schools, or 12% of British final-year students in 2003) were
      compared to 1455 students from 62 U.S. schools (overall response rate 62%, or 9%
      of U.S. final-year students in 2001). Compared to U.S. students, British medical
      students reported more training in palliative care, more positive clinical
      encounters in palliative care, greater educational training in specific end-of
      life topics, greater preparedness for caring for patients at the end of life, a
      culture within medicine more favorable toward palliative care, and attitudes more
      consistent with support for palliative care (all at statistically significant
      levels of p < 0.0001). CONCLUSIONS: Palliative care education, from the
      perspective of medical students, appears to be more effective in Britain than in
      the United States. Our findings suggest three changes with the potential to
      improve U.S. palliative care education of medical students: increasing required
      course-work in palliative care, increasing the number of palliative medicine role
      models, and creating robust academic palliative medicine departments to lead and
      support these advances.

PMID- 18095816
TI  - Analgesic usage in cancer: the evolution of a palliative medicine physician.

PMID- 18095817
TI  - The pharmacologic management of cancer pain.
AB  - The under treatment of cancer pain is still a major issue in both oncology and
      palliative medicine. The initial availability of opioids is seen as an important
      philosophical step forward in the pharmacological treatment of cancer pain, one
      for which there continues to be considerable barriers within regulatory and
      medical domains. Knowledge of the key pharmacological properties of the multiple
      opioids available will assist in both improved analgesia and side effects.
      Understanding the mechanisms of pain is important in terms of treatment,
      especially in terms of the choice of co-analgesic agents. Much of the work
      obtained from the study of cancer patients is applicable to the non cancer
      populations, as is work performed in non cancer patients with neuropathic pain.

PMID- 18095818
TI  - Evolving medicolegal issues in palliative medicine.
AB  - The successful practice of hospice and palliative medicine requires basic
      knowledge of its medicolegal aspects. In this paper, we review several recent
      legal cases that highlight important, evolving legal issues in palliative
      medicine. These issues include efforts to change to advance directive laws after
      the Schiavo conflict, the Attorney General's challenge to Oregon's physician
      assisted dying law, and the emergence of a tort for inadequate pain management.
      Despite conflicting attitudes about key issues in end-of-life care, the courts'
      decisions in these cases have consistently advanced the interests of hospice and
      palliative care practitioners.

PMID- 18095819
TI  - Prognostication in patients receiving dialysis #191.

PMID- 18095820
TI  - Opioid use in renal failure #161.

PMID- 18095824
TI  - Would you refer this patient to hospice? An evaluation of tools for determining
      life expectancy in end-stage dementia.

PMID- 18095834
TI  - Vaccination in Brazilian HIV-infected adults: a cross-sectional study.
AB  - HIV-infected patients are at risk for vaccine-preventable infections. The
      Brazilian National Immunization Program provided recommendations for this
      population. However, the vaccine coverage reached by this program is unknown.
      This study aimed at evaluating the vaccine coverage of HIV-infected adults
      followed at Hospital das Clinicas, University of Sao Paulo School of Medicine.
      Data were collected on age, gender, mode of HIV transmission, Centers for Disease
      Classification 1993 classification (CDC/93), antiretrovirals, CD4 count, HIV
      viral load, and immunization charts, from April 2003 to August 2004. We
      interviewed 144 randomly selected patients, 74% male; mean age, 39.95 years; CDC
      classification: A, 40.6%; B, 19.6%; and C, 39.9%. Most of patients were
      undergoing highly active antiretroviral therapy (HAART; 86.8%). Mean CD4 count
      442.6 cells/mm3. Viral load less than 400 copies per milliliter in 59.4% of
      patients. Only 36.1% of patients were adequately immunized for
      diphtheria/tetanus, 54.9% for pneumococcus, 24.3% for flu, and 76.9% for
      hepatitis B. In relation to live attenuated vaccines, 5 patients received
      measles, mumps, and rubella vaccine and 7 patients yellow fever vaccine. Two
      patients were vaccinated against yellow fever despite CD4 less than 200 cell/mm3.
      We verified poor vaccine coverage in HIV-infected patients. Vaccination campaigns
      and incorporation of vaccine rooms in sexually transmitted disease (STD)/AIDS
      clinics could improve this situation.

PMID- 18095835
TI  - Viro-immunologic response to ritonavir-boosted or unboosted atazanavir in a large
      cohort of multiply treated patients: the CARe Study.
AB  - Currently, comparative data able to define the potency of boosted versus
      unboosted atazanavir in highly pretreated HIV-infected patients are limited.
      Specifically, in clinical practice it is very important to establish whether
      atazanavir-boosting with ritonavir warrants potency and efficacy that overcome
      the profile of unboosted drug. For this reason, our goal was to evaluate viro
      immunologic determinants of response to atazanavir, in unboosted ATV400 or
      boosted ATV300/r formulation, from baseline to week 48 in highly pretreated HIV
      infected patients enrolled in a prospective observational Italian study. Data
      from 354 patients included in an atazanavir "Early Access Program" (AI424-900)
      with baseline viremia 500 copies per milliliter or more and with an available
      virologic follow-up were examined using as-treated analysis. Of these, 200
      (56.5%) and 154 (43.5%), respectively, received regimens containing ATV300/r or
      ATV400. Virologic success (VS) was defined as reaching viremia of less than 500
      copies per milliliter during follow-up. Estimated median time to VS was 8 weeks
      in the ATV300/r group and 13 weeks in the ATV400 group. Proportion of patients
      achieving VS was higher in the ATV300/r group than in ATV400 group at week 12
      (66% versus 47%), as well as at week 48 (86% versus 64%). At multivariate Cox
      regression, receiving ATV300/r dosing was independently associated with increased
      probability of achieving VS [adjusted hazard ratio (AHR): 1.57; 95% confidence
      interval (CI): 1.19-2.06]. Conversely, CDC stage C, higher baseline viral load,
      and more experience with protease inhibitors (PIs) were associated with poorer
      virologic response. In an unselected population of highly pretreated HIV-infected
      individuals, receiving atazanavir as part of antiretroviral regimen results in
      effective virologic response and immunologic recovery. The antiviral efficacy of
      atazanavir is greater when boosted with low-dose ritonavir.

PMID- 18095836
TI  - Bilateral renal aspergillosis in a patient with AIDS: a case report and review of
      reported cases.
AB  - Renal aspergillosis is an extremely uncommon complication in HIV-infected
      patients. In general, prognosis is poor and the need for nephrectomy is
      emphasized. We report the case of a 37-year-old patient with AIDS since April
      2003 (CD4 count 10 cells/mm(3), a high viral load, Candida esophagitis, bilateral
      pneumonia, HIV encephalopathy). Treatment with zidovudine, lamivudine,
      nevirapine, and lopinavir/ritonavir was started. Adherence to this medication
      proved to be a problem, but after 18 weeks of HAART the CD4 count was 110
      cells/mm(3) and viral load was undetectable. One year later, he presented with
      hematuria and flank pain. Computed tomography (CT) scan revealed multiple lesions
      in both kidneys. Cultures of the abscess aspirates yielded Aspergillus fumigatus.
      Our review of 18 reported cases shows that prognosis of renal aspergillosis is
      poor if nephrectomy is not performed. However, in the present case a conservative
      approach was chosen to avoid life-long dialysis. The patient was treated
      successfully with a combination of voriconazole, percutaneous drainage, and
      highly active antiretroviral therapy (HAART). Renal function was completely
      preserved. Reported cases from the literature of renal aspergillosis in HIV
      infected patients are summarized in this paper.

PMID- 18095837
TI  - Self-Reported adherence to antiretroviral treatment among HIV-infected people in
      Central China.
AB  - Although the number of patients receiving antiretroviral (ARV) therapy in Central
      China is expanding, little is known about their medication adherence. The purpose
      of this study was to: (1) describe adherence prevalence among patients receiving
      free ARV in south central China; (2) identify factors associated with adherence;
      (3) compare 3 self-report measures of adherence in this population. A cross
      sectional survey was conducted at seven free treatment sites in Hunan, Hubei, and
      Anhui Provinces. Adherence measures included direct questioning regarding the
      number of doses taken in the 7 days prior to interview, the Community Programs
      for Clinical Research on AIDS (CPCRA) Adherence Self-Report questionnaire, and a
      7-day visual analogue scale. Subjects comprised all patients returning for
      monthly ARV follow-up at each site between April and July 2006. Among the 308
      subjects, 244 (79%) lived in the countryside. One hundred seventy (55%) had been
      on ARV over 1 year. No regimen included a protease inhibitor. Two hundred forty
      four (80%) reported taking more than 90% of prescribed doses in the previous 7
      days. Sixty-four (20%) subjects reported missing at least 1 dose in that period.
      The three measures of self-reported adherence were highly correlated. On
      multivariate analysis, current heroin use (odds ratio [OR] = 2.5; 95% confidence
      interval [CI] 1,6, p = 0.05) and nonuse of reminders such as cell phone alarms,
      wall charts, or TV programs (OR 6; 95% CI 3, 11; p = 0.001) were associated with
      90% or less adherence. Adherence to ARV in Central China is similar to elsewhere
      in the world. The 20% of subjects who reported taking 90% or fewer doses are of
      concern in view of the potential for non-nucleoside reverse transcriptase
      inhibitor resistance and lack of protease inhibitor back-up regimens. Substance
      abuse treatment will be an essential element of successful AIDS treatment in
      China. Prospective studies are needed to evaluate the efficacy of reminder
      devices to improve adherence in this population and to describe the prevalence
      and incidence of ARV resistance.

PMID- 18095838
TI  - Concurrent HIV/AIDS diagnosis increases the risk of short-term HIV-related death
      among persons newly diagnosed with AIDS, 2002-2005.
AB  - Despite the overall effectiveness and availability of highly active
      antiretroviral therapy (HAART), 1500 HIV-related deaths still occur annually in
      New York City. In considering ways to further reduce deaths, we assessed the
      contribution of concurrent HIV/AIDS diagnosis to HIV-related mortality in New
      York City among persons newly diagnosed with AIDS. We used Cox regression to
      conduct a retrospective cohort analysis of HIV-related mortality among 15,211
      residents age 13+ reported with AIDS to the population-based HIV/AIDS registry
      between January 2002 and June 2005. Concurrent HIV/AIDS diagnosis was defined as
      a diagnosis of AIDS occurring within 1 month of initial diagnosis of HIV. HIV
      related mortality was 20.2% among persons diagnosed concurrently and 12.2% among
      those diagnosed nonconcurrently (p < 0.0001). Concurrent HIV/AIDS was associated
      with more than twice the risk of HIV-related death within the 4 months after
      diagnosis (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.94-2.65) but no
      increased risk thereafter (HR 1.12, 95% CI 0.77-1.61). Other significant
      predictors of death included injection drug use and birth in the Caribbean or
      Latin America. After 4 years 11.9% of all HIV-related deaths were attributable to
      a concurrent HIV/AIDS diagnosis. Public health initiatives that facilitate early
      diagnosis of HIV may reduce HIV-related mortality by giving people the
      opportunity to initiate care and begin treatment with HAART before
      immunosuppression places them at risk for opportunistic illness and death.

PMID- 18095840
TI  - Medical care of HIV-infected individuals in Poland: impact of stigmatization by
      health care workers.

PMID- 18095839
TI  - A qualitative study among injection drug using women in Rhode Island: attitudes
      toward testing, treatment, and vaccination for hepatitis and HIV.
AB  - HIV and hepatitis C virus infection are serious and prevalent health conditions
      among many women who inject drugs. Qualitative interviews with 20 injection drug
      using women at a short term drug treatment center in Rhode Island revealed six
      primary barriers and facilitators for testing and receiving results and treatment
      for hepatitis and HIV, as well as for hepatitis vaccination. The primary barriers
      were prioritization of drug use; low level of disease-specific knowledge;
      stigmatization; accessibility of testing, results and treatment; and
      psychological factors. The primary facilitator was interest in promoting one's
      health. Our findings indicate that injection drug using women experience multiple
      barriers to HIV and hepatitis testing, results, treatment and vaccination.
      Methods for improving the motivators for health, facilitating infectious disease
      prevention, and decreasing unnecessary disease complications of injection drug
      using women need to be utilized. These methods should include strategies that
      minimize stigma and facilitate accessibility of health care.

PMID- 18095841
TI  - Predictors of the initiation of HIV postexposure prophylaxis in Rhode Island
      emergency departments.
AB  - The objective of this study was to elucidate factors that predicted the
      initiation of HIV postexposure prophylaxis (PEP) for blood or body fluid
      exposures evaluated at Rhode Island emergency departments (EDs). The study
      involved a retrospective review of patient visits to all civilian Rhode Island
      EDs for these exposures from 1995 to mid-2001. Multivariate logistic regression
      models were created to evaluate predictors of the offering and the acceptance and
      receipt of HIV PEP from 1996 to 2001. The search identified 3622 patients who
      sustained a blood or body fluid exposure. Of these, 43.8% were health care
      workers (HCWs) and 57.2% were not HCWs. Most (52.0%) of the exposures were
      nonsexual. HIV PEP was offered to 21.0% and accepted and received by 9.4% of all
      patients. HIV PEP was offered more often after significant exposures, exposures
      to known HIV-infected sources, when time elapsed after the exposure was shorter,
      if the patients were HCWs, adults, presented to a teaching hospital, presented
      during the latter years of the study, or sustained nonsexual exposures. Once
      offered HIV PEP, patients who were male, adult, sustained a significant exposure,
      knew the source was HIV infected, sustained a nonsexual exposure, or were HCWs
      had a greater odds of accepting and receiving HIV PEP. Even when controlling for
      exposure significance, HIV status, and time elapsed since the exposure, several
      factors such as gender and type of hospital that are unrelated to the exposure
      appeared to influence the initiation of HIV PEP. ED providers should ensure that
      these factors do not inappropriately restrict its initiation.

PMID- 18095842
TI  - Nanoneuroscience: emerging concepts on nanoneurotoxicity and nanoneuroprotection.

PMID- 18095844
TI  - Use of 3D beta-tricalcium phosphate (Vitoss) scaffolds in repairing bone defects.
AB  - Vitoss is the most porous (90%) of a number of beta-tricalcium phosphate
      osteoconductive bone fillers. Its inherent limitations are those of the calcium
      phosphate class, being a purely osteoconductive product without inherent
      structural stability and with a moderate resorption rate. Currently, a number of
      additives, composites and related compounds are under study at various stages. In
      animal experiments, Vitoss performs well in comparison with other synthetic
      grafts, and with marrow added in various ways, it rivals autograft. Clinical
      efficacy is established for Vitoss as a spinal graft extender, as well as for
      periodontal, dental and orthopedic tumor defects. Apart from recombinant human
      platelet-derived growth factor, clinical data is lacking on the addition of bone
      marrow, stem cells and growth factors.

PMID- 18095845
TI  - Functional gold nanoparticles as photothermal agents for selective-killing of
      pathogenic bacteria.
AB  - AIMS: Our aim was to demonstrate that functional gold nanoparticles can be used
      as photothermal agents for the selective killing of pathogenic bacteria.
      MATERIALS & METHODS: Gold nanoparticles with polygonal shapes, capable of
      absorbing near infrared (NIR) light, were generated through a photochemical
      reaction. Vancomycin, which can bind with the terminal D-Ala-D-Ala moieties of
      the peptide units of pathogen cell walls, was immobilized on the surface of the
      gold nanoparticles. The vancomycin-bound gold nanoparticles were used as the
      photothermal agents for the inhibition of pathogenic bacteria growth, under
      irradiation of NIR light (808 nm). RESULTS & DISCUSSION: We have demonstrated
      that vancomycin-bound gold nanoparticles are capable of selective-binding onto
      the cell walls of pathogenic bacteria. A large portion (>99%) of bacteria
      targeted by the gold nanoparticles was destroyed under illumination by NIR light
      within 5 min owing to suffering from heating. CONCLUSIONS: This photothermal
      approach is effective for the inhibition of pathogenic bacteria cell growth,
      including Gram-positive bacteria, Gram-negative bacteria and antibiotic-resistant
      bacteria.

PMID- 18095846
TI  - Characterization of nanoparticles for therapeutics.
AB  - Nanotechnology offers many advantages to traditional drug design, delivery and
      medical diagnostics; however, nanomedicines present considerable challenges for
      preclinical development. Nanoparticle constructs intended for medical
      applications consist of a wide variety of materials, and their small size, unique
      physicochemical properties and biological activity often require modification of
      standard characterization techniques. A rational characterization strategy for
      nanomedicines includes physicochemical characterization, sterility and
      pyrogenicity assessment, biodistribution (absorption, distribution, metabolism
      and excretion [ADME]) and toxicity characterization, which includes both in vitro
      tests and in vivo animal studies. Here, we highlight progress for a few methods
      that are uniquely useful for nanoparticles or are indicative of their toxicity or
      efficacy.

PMID- 18095847
TI  - Targeted nanomaterials for radiotherapy.
AB  - Nanomaterials have garnered increasing interest recently as potential therapeutic
      drug-delivery vehicles. Among the existing nanomaterials are the pure carbon
      based particles, such as fullerenes and nanotubes, various organic dendrimers,
      liposomes and other polymeric compounds. These vehicles have been decorated with
      a wide spectrum of target-reactive ligands, such as antibodies and peptides,
      which interact with cell-surface tumor antigens or vascular epitopes. Once
      targeted, these new nanomaterials can then deliver radioisotopes or isotope
      generators to the cancer cells. Here, we will review some of the more common
      nanomaterials under investigation and their current and future applications as
      drug-delivery scaffolds with particular emphasis on targeted cancer radiotherapy.

PMID- 18095848
TI  - Towards biomedical applications for nucleic acid nanodevices.
AB  - DNA and RNA can be used to construct artificial nanodevices with strong potential
      for future biomedical applications. DNA nanodevices can function as biosensors,
      which detect and report the presence of proteins and naturally occurring nucleic
      acids, such as mRNA or microRNAs. Complex sensors can be realized by supporting
      DNA devices with DNA-based information processing. Artificial DNA-based reaction
      networks can be created that amplify molecular signals or evaluate logical
      functions to report the simultaneous presence of several disease-related
      molecules. Other applications for DNA nanodevices are found in controlled release
      and drug delivery. DNA can be used to build nanocontainers for drugs or
      switchable hydrogels, which can trap and release compounds. For in vivo
      applications of DNA nanodevices, techniques for efficient packaging and delivery
      have been developed and the first examples of intracellular RNA-based nanodevices
      have already been demonstrated.

PMID- 18095849
TI  - Delivery of nano-objects to functional sub-domains of healthy and failing cardiac
      myocytes.
AB  - Cardiovascular disease, including heart failure, is one of the leading causes of
      mortality in the world. Delivery of nano-objects as carriers for markers, drugs
      or therapeutic genes to cellular organelles has the potential to sharply increase
      the efficiency of diagnostic and treatment protocols for heart failure. However,
      cardiac cells present special problems to the delivery of nano-objects, and the
      number of papers devoted to this important area is remarkably small. The present
      review discusses fundamental aspects, problems and perspectives in the delivery
      of nano-objects to functional sub-domains of failing cardiomyocytes. What size
      nano-objects can reach cellular sub-domains in failing hearts? What are the
      mechanisms for their permeation through the sarcolemma? How can we improve the
      delivery of nano-objects to the sub-domains? Answering these questions is
      fundamental to identifying cellular targets within the failing heart and the
      development of nanocarriers for heart-failure therapy at the cellular level.

PMID- 18095850
TI  - Imaging gene delivery with fluorescence microscopy.
AB  - Gene delivery offers the promise of treatment for a range of human diseases.
      Although carried out initially with modified viruses, the use of synthetic
      molecules, including polymers, lipids and peptides, has extended the
      possibilities greatly for rationally designed vectors tailored to individual gene
      delivery applications. Underlying the rational design of gene-delivery vectors is
      the need to understand the individual steps of the gene-delivery pathway. Using
      new methods in fluorescence microscopy, it is now possible to isolate individual
      steps along the gene-delivery pathway to characterize the mechanisms of cellular
      binding, cellular internalization and nuclear entry. This review describes the
      advances made in the gene-delivery field with the assistance of fluorescence
      microscopy. The focus of this review is the use of synthetic gene-delivery
      vectors, especially polyethylenimine, and the live-cell imaging and single
      particle tracking techniques that reveal the intracellular dynamics of the gene
      delivery process.

PMID- 18095851
TI  - Nanosurfaces and nanostructures for artificial orthopedic implants.
AB  - Nanomaterials and structures, such as nanoparticles, nanofibers, nanosurfaces,
      nanocoatings, nanoscaffolds and nanocomposites, are considered for various
      applications in orthopedics and traumatology. This review looks at proposed
      nanotechnology inspired applications for implants from the perspective of the
      orthopedic industry. Investigations support consistently the theory that most
      nanomaterials in various physical forms are able to enhance the cell response
      selectively for biological tissue integration or increase the strength and wear
      resistance of current orthopedic materials. At this stage, most of the studies
      are at the laboratory scale or in early in vivo testing. Significant basic and
      applied research and development is needed to realize their full clinical
      potential and biological, manufacturing, economic and regulatory issues have to
      be addressed. Nevertheless, a crucial factor for success is well-coordinated
      multimethod and multidiscipline teamwork with profound industrial and medical
      expertise.

PMID- 18095852
TI  - Solid-state nanopore technologies for nanopore-based DNA analysis.
AB  - Nanopore-based DNA analysis is a new single-molecule technique that involves
      monitoring the flow of ions through a narrow pore, and detecting changes in this
      flow as DNA molecules also pass through the pore. It has the potential to carry
      out a range of laboratory and medical DNA analyses, orders of magnitude faster
      than current methods. Initial experiments used a protein channel for its pre
      defined, precise structure, but since then several approaches for the fabrication
      of solid-state pores have been developed. These aim to match the capabilities of
      biochannels, while also providing increased durability, control over pore
      geometry and compatibility with semiconductor and microfluidics fabrication
      techniques. This review summarizes each solid-state nanopore fabrication
      technique reported to date, and compares their advantages and disadvantages.
      Methods and applications for nanopore surface modification are also presented,
      followed by a discussion of approaches used to measure pore size, geometry and
      surface properties. The review concludes with an outlook on the future of solid
      state nanopores.

PMID- 18095853
TI  - Inorganic materials for bone repair or replacement applications.
AB  - In recent years, excipient systems have been used increasingly in biomedicine in
      reconstructive and replacement surgery, as bone cements, drug-delivery vehicles
      and contrast agents. Particularly, interest has been growing in the development
      and application of controlled pore inorganic ceramic materials for use in bone
      replacement and bone-repair roles and, in this context, attention has been
      focused on calcium-phosphate, bioactive glasses and SiO2- and TiO2-based
      materials. It has been shown that inorganic materials that most closely mimic
      bone structure and surface chemistry most closely function best in bone
      replacement/repair and, in particular, if a substance possesses a macroporous
      structure (pores and interconnections >100 microm diameter), then cell
      infiltration, bone growth and vascularization can all be promoted. The surface
      roughness and micro/mesoporosity of a material have also been observed to
      significantly influence its ability to promote apatite nucleation and cell
      attachment significantly. Pores (where present) can also be packed with
      pharmaceuticals and biomolecules (e.g., bone morphogenetic proteins [BMPs], which
      can stimulate bone formation). Finally, the most bio-efficient - in terms of
      collagen formation and apatite nucleation - materials are those that are able to
      provide soluble mineralizing species (Si, Ca, PO(4)) at their implant sites
      and/or are doped or have been surface-activated with specific functional groups.
      This article presents the context and latest advances in the field of bone-repair
      materials, especially with respect to the development of bioactive glasses and
      micro/mesoporous and macroporous inorganic scaffolds. It deals with the possible
      methods of preparing porous pure/doped or functionalized silicas or their
      composites, the studies that have been undertaken to evaluate their abilities to
      act as bone repair scaffolds and also presents future directions for work in that
      context.

PMID- 18095854
TI  - Engineered nanomaterials in soils and water: how do they behave and could they
      pose a risk to human health?
AB  - It is inevitable that, during their use, engineered nanoparticles will be
      released into soils and waters. There is therefore increasing concern over the
      potential impacts of engineered nanoparticles in the environment on aquatic and
      terrestrial organisms and on human health. Once released into the environment,
      engineered nanoparticles will aggregate to some degree; they might also associate
      with suspended solids, sediment, be accumulated by organisms and enter drinking
      water sources and food materials. These fate processes are dependent on the
      characteristics of the particle and the characteristics of the environmental
      system. A range of ecotoxicological effects have also been reported, including
      effects on microbes, plants, invertebrates and fish. Although available data
      indicate that current risks of engineered nanoparticles in the environment to
      environmental and human health are probably low, our knowledge of the potential
      impacts of engineered nanoparticles in the environment on human health is still
      limited. There is therefore a need for continued work to develop an understanding
      of the exposure levels for engineered nanoparticles in environmental systems and
      to begin to explore the implications of these levels in terms of the ecosystem
      and human health. This will require research in a range of areas, including
      detection and characterization, environmental fate and transport, ecotoxicology
      and toxicology.

PMID- 18095855
TI  - Electrospun nanostructured scaffolds for tissue engineering applications.
AB  - Despite being known for decades (since 1934), electrospinning has emerged
      recently as a very widespread technology to produce synthetic nanofibrous
      structures. These structures have morphologies and fiber diameters in a range
      comparable with those found in the extracellular matrix of human tissues.
      Therefore, nanofibrous scaffolds are intended to provide improved environments
      for cell attachment, migration, proliferation and differentiation when compared
      with traditional scaffolds. In addition, the process versatility and the highly
      specific surface area of nanofiber meshes may facilitate their use as local drug
      release systems. Common electrospun nanofiber meshes are characterized by a
      random orientation. However, in some special cases, aligned distributions of the
      fibers can be obtained, with an interconnected microporous structure. The
      characteristic pore sizes and the inherent planar structure of the meshes can be
      detrimental for the desired cell infiltration into the inner regions, and
      eventually compromise tissue regeneration. Several strategies can be followed to
      overcome these limitations, and are discussed in detail here.

PMID- 18095856
TI  - Novel nanocrystals as a platinum-delivery vehicle for chemotherapy.

PMID- 18095857
TI  - Everything is illuminated ... with quantum dots.

PMID- 18095858
TI  - Nanovector.
AB  - Nanovector was founded in 2001 and is one of the companies that first began
      working in the nanomedicine field in Italy, having a specific focus on developing
      its technical platform for drug-delivery applications. Proprietary lipid
      nanocarriers, microemulsions and Solid Lipid Nanoparticles have been tested over
      recent years, delivering different drugs by different administration routes: in
      this profile, a short overview of our main results will be given. The delivery
      system platform has shown and confirmed promising characteristics. Focusing on
      solid lipid nanoparticles, a leading possibility as a carrier for hydrophobic and
      hydrophilic drugs, we have tested four administration routes (intravenous,
      oral/duodenal, eye topical and transdermal), their rapid internalization into
      cells, their in vivo targeting to areas not usually reached (brain and eye
      posterior globe) and their ability to cross the intestinal mucosa, thus enabling
      administration of drugs from intravenous to oral. Nanovector aims to exploit the
      proprietary technical platform to develop therapeutics in areas with strong unmet
      medical needs and promising market opportunities.

PMID- 18095859
TI  - Safety and efficacy of supracostal access in percutaneous renal surgery.
AB  - BACKGROUND AND PURPOSE: During percutaneous renal surgery, subcostal access is
      preferred because it carries no risk of injury to either the lungs or pleura.
      However, in some situations, a supracostal approach may provide more direct
      access and achieve a more satisfactory result than the subcostal approach. In
      this prospective study, we evaluated the safety and efficacy of supracostal
      approaches in percutaneous renal surgery. MATERIALS AND METHODS: Between 2004 and
      2006, 30 patients underwent percutaneous renal surgery with a supracostal
      approach either as the sole or as a secondary access. The indications were
      staghorn stones, upper caliceal stones, upper ureteral stones, secondary
      ureteropelvic junction obstruction, disturbed lower caliceal anatomy, and high
      lying kidneys. The puncture was above the eleventh rib in six procedures and
      above the twelfth rib in 24 procedures. All patients were examined for equal air
      entry on both sides of the chest, and all had chest radiography performed
      immediately after surgery to exclude pneumothorax or hydrothorax. Bleeding was
      assessed with evaluation of preoperative and postoperative hemoglobin, levels and
      vital signs; urine was also examined for gross hematuria. A routine nephrostogram
      was obtained for all patients. RESULTS: Supracostal was the sole access in 63.3%
      of patients and a secondary access in 36.7% of patients. Intraoperatively,
      bleeding occurred in one patient. Hydrothorax in another patient necessitated
      insertion of an intercostal chest drain. A renopleural fistula developed in
      another patient 2 days postoperatively that necessitated placement of a chest
      drain and Double J stent. Access in both patients with pleural complications had
      been above the eleventh rib. The mean drop in hemoglobin level was 0.79 +/- 0.72
      g/dL. Our overall stone-free rate was 88.9%. CONCLUSION: Supracostal access above
      the twelfth rib is relatively safe; however, access above the eleventh rib should
      be limited to necessity because a higher incidence of pleural complications can
      be expected. A chest radiograph should be obtained immediately postoperatively
      for early detection of hydrothorax or pneumothorax.

PMID- 18095860
TI  - Rationale and feasibility study of a mechanical model for the testing of material
      fatigue in metal ureteral stents.
AB  - BACKGROUND: Stents are used abundantly to maintain ureteral patency. The majority
      are plastic tubes that adjust easily to upper urinary-tract motion. Recently, a
      coiled-wire lumenless stent was introduced (ZebraStent, Neo Medical, Munich,
      Germany) to facilitate expulsion of stone fragments after lithotripsy. Its metal
      core is composed of Nitinol, with the soft J ends being of titanium. The thin
      shape considerably increases the extraluminal space. The ZebraStent stretches the
      ureter and also provides a surface for the fragments to glide along. In our 18
      month experience with the ZebraStent, two of them fractured along the shaft. We
      sought to learn whether this complication resulted from a defect in stent design
      or from material fatigue secondary to constant movement. MATERIALS AND METHODS:
      Our model is powered by an electric motor that produces a constant displacement
      similar to stent movements in vivo. The whole ZebraStent is embedded in a 37
      degrees C waterbath to simulate physiological conditions within the ureter. We
      used an average displacement of 16 mm. The average frequency of ventilatory-cycle
      simulation was 20 times that in vivo, allowing us to collect data in a shorter
      time. RESULTS: All 10 stents broke within the proximal Nitinol shaft at the
      equivalent of 4 to 6 months (125-179 days). CONCLUSIONS: Our preliminary results
      show that all stents break after the equivalent of 4 or more months. The fact
      that this occurs in the homogenous proximal Nitinol shaft rather than at the
      welding point between the shaft and the titanium curl implies that breakage is
      secondary to material fatigue and not design error. Extensive testing is under
      way to confirm material fatigue as the cause of breakage. We hope to determine a
      safe dwelling time for these stents, which at the moment should not exceed 3
      months.

PMID- 18095861
TI  - Bladder neck contracture after robot-assisted laparoscopic radical prostatectomy:
      evaluation of incidence and risk factors and impact on urinary function.
AB  - PURPOSE: Bladder neck contracture (BNC) after radical prostatectomy has been
      reported to occur in 5% to 32% of men after open radical retropubic prostatectomy
      (RRP) and 0% to 3% after laparoscopic RRP. Optimal anastomotic closure involves
      creating a watertight, tension-free anastomosis with well-vascularized, mucosal
      apposition and correct realignment of the urethra. The cause of BNC is poorly
      understood; however, it is likely related to multiple factors, including
      excessive luminal narrowing at the site of reconstruction, local tissue ischemia,
      failed mucosal apposition, and urinary leakage. In this large series of patients
      who underwent robot-assisted laparoscopic radical prostatectomy (RLRP), we report
      the incidence of BNC, evaluate the influence of age, body mass index (BMI),
      estimated blood loss (EBL), surgical time, and prostate weight on its development
      and assess follow-up urinary function. MATERIALS AND METHODS: Between February
      2003 and July 2006, 650 consecutive men underwent RLRP at our institution.
      Patients with aborted or open conversion procedures were excluded from analysis.
      The mean overall follow-up for the remaining 634 patients was 19.5 months.
      Patients presenting with symptoms of outlet obstruction were evaluated with
      cystoscopy to confirm a BNC. Comparisons of age, BMI, EBL, operative time, and
      prostate weight were performed using the Student t-test and chi-square analysis.
      RESULTS: BNC was the diagnosis in seven patients (1.1%), with a mean time of
      presentation of 4.8 (3-12) months postoperatively. The BNC patients had
      comparable mean age, BMI, prostate weight, and EBL to the non-BNC cohort. Their
      operative time, however, was significantly longer (283 v 225 min, P = 0.04).
      CONCLUSIONS: The incidence of BNC after radical prostatectomy is 1.1% in a large
      series of men undergoing RLRP. The diagnosis was made within 1 year. No
      significant impact on urinary continence or quality-of-life urinary function was
      observed after BNC management. A running anastomosis, better visualization,
      improved instrument maneuverability, and decreased blood loss may account for
      such a low rate.

PMID- 18095862
TI  - Does the metabolic syndrome or its components affect the outcome of percutaneous
      nephrolithotomy?
AB  - PURPOSE: Metabolic syndrome is a cluster of cardiovascular disease risk factors.
      We assessed the impact of these medical disorders on the outcome of percutaneous
      nephrolithotomy (PCNL). PATIENTS AND METHODS: Data from 430 consecutive PCNL
      procedures were retrospectively reviewed. The presence of serum lipid
      abnormalities (SLA), hypertension (HT), diabetes (DM), and obesity was
      investigated. Patients were determined to have the metabolic syndrome according
      to the definition of the International Diabetes Federation. Success rate, need
      for auxiliary procedures, and major complication rates of PCNL were analyzed
      separately for patients with or without DM, SLA, HT, obesity, and the metabolic
      syndrome, and were compared. RESULTS: SLA, HT, and DM were observed in 123
      (28.6%), 108 (25.1%), and 44 (10.2%) patients, respectively. Body mass index was
      >30 kg/m2 in 74 (17.2%) patients. Metabolic syndrome was diagnosed in 41 (9.5%)
      patients. An overall success rate of 96.3% for PCNL was achieved. Success rates
      were not significantly (P > 0.05) influenced by the presence of SLA, HT, DM,
      obesity, or the metabolic syndrome. Major complications were encountered in 49
      (11.4%) patients and were 2.5 to 2.7 times more common in patients with DM, HT,
      and the metabolic syndrome. In patients with DM, auxiliary treatment alternatives
      were necessary in 20.5%, while they were indicated in 10.9% of patients without
      DM (P = 0.046). Presence of the metabolic syndrome was also associated with an
      increased necessity for auxiliary treatments after PCNL (P = 0.048). CONCLUSIONS:
      Our results indicate that the metabolic syndrome and its components (DM and HT)
      significantly augment auxiliary treatment and complication rates after PCNL.

PMID- 18095863
TI  - Totally tubeless percutaneous nephrolithotomy.
AB  - PURPOSE: To establish if totally tubeless percutaneous nephrolithotomy (PCNL) is
      a safe management technique. PCNL is a well-established option for upper tract
      stones. The procedure traditionally concludes with the placement of a nephrostomy
      drainage tube but in those patients in whom there has been minimal blood loss and
      complete stone clearance, it may not be necessary to place a nephrostomy.
      PATIENTS AND METHODS: Totally tubeless PCNL was performed in uncomplicated cases,
      when there was no significant bleeding or residual stone load, an intact
      pelvicaliceal system, and no evidence of a residual ureteral stone. RESULTS: 100
      procedures were analyzed during a 10-year period from 1996 to 2006. The mean
      stone size was 15.9 mm (range 7-40 mm). Mean residual stone load was 1.74 mm
      (range 1-10 mm). Access was considered difficult in 2%. Transfusion rate was 1%
      with a mean fall in hemoglobin of 1.4 g/dL ([-0.4] - [+5.6] g/dL), and a mean
      rise in creatinine level of 0.3 micromol/L ([-43] - [+52] micromol/L). The minor
      sepsis rate was 5%, and the major sepsis rate was 1%. The readmission rate was
      1%. The mean length of stay was 2.9 days (range 1-10 d). Secondary treatment was
      required in 5%, and stone clearance rate at 3 months was 90%. CONCLUSION: This
      study demonstrates that PCNL without nephrostomy or stent is a safe and well
      tolerated procedure in selected patients. It is the authors' belief that totally
      tubeless PCNL may be considered an accepted standard of care for selected
      patients, and it is possible to reserve placement of a nephrostomy tube or
      internal ureteral stent for specific indications.

PMID- 18095864
TI  - A counterintuitive approach to treat enzyme deficiencies: use of enzyme
      inhibitors for restoring mutant enzyme activity.
AB  - Pharmacological chaperone therapy is an emerging counterintuitive approach to
      treat protein deficiencies resulting from mutations causing misfolded protein
      conformations. Active-site-specific chaperones (ASSCs) are enzyme active-site
      directed small molecule pharmacological chaperones that act as a folding template
      to assist protein folding of mutant proteins in the endoplasmic reticulum (ER).
      As a result, excessive degradation of mutant proteins in the ER-associated
      degradation (ERAD) machinery can be prevented, thus restoring enzyme activity.
      Lysosomal storage disorders (LSDs) are suitable candidates for ASSC treatment, as
      the levels of enzyme activity needed to prevent substrate storage are relatively
      low. In addition, ASSCs are orally active small molecules and have potential to
      gain access to most cell types to treat neuronopathic LSDs. Competitive enzyme
      inhibitors are effective ASSCs when they are used at sub-inhibitory
      concentrations. This whole new paradigm provides excellent opportunity for
      identifying specific drugs to treat a broad range of inherited disorders. This
      review describes protein misfolding as a pathophysiological cause in LSDs and
      provides an overview of recent advances in the development of pharmacological
      chaperone therapy for the diseases. In addition, a generalized guidance for the
      design and screening of ASSCs is also presented.

PMID- 18095865
TI  - Reassessing the role of a 3'-UTR-binding translational inhibitor in regulation of
      circadian bioluminescence rhythm in the dinoflagellate Gonyaulax.
AB  - The nightly bioluminescence of the dinoflagellate Gonyaulax is a circadian rhythm
      caused by the presence in cells of specialized bioluminescent organelles, termed
      scintillons, containing the reaction catalyst luciferase, the substrate luciferin
      and a luciferin-binding protein (LBP). LBP levels increase at the start of the
      night phase because of increased protein synthesis rates in vivo, and this
      regulation has been ascribed to circadian binding of an inhibitory protein factor
      binding to the 3' untranslated region (UTR) of lbp mRNA at times when LBP is not
      normally synthesized. To purify and characterize the binding factor, the
      electrophoretic mobility shift assays and UV crosslinking experiments used to
      first characterize the factor were repeated. However, neither these protocols nor
      binding to biotinylated RNA probes confirmed the presence of a specific circadian
      RNA-binding protein. Furthermore, neither RNA probe screening of a cDNA library
      expressed in bacteria nor three-hybrid assays in yeast were successful in
      isolating a cDNA encoding a protein able to bind specifically to the lbp 3'UTR.
      Taken together, these results suggest that alternative mechanisms for regulating
      lbp translation should now be examined.

PMID- 18095866
TI  - Cloning, functional analysis, and mitochondrial localization of Trypanosoma
      brucei monothiol glutaredoxin-1.
AB  - African trypanosomes encode three monothiol glutaredoxins (1-C-Grx1 to 3). 1-C
      Grx1 has a putative CAYS active site and Cys181 as single additional cysteine.
      The recombinant protein forms non-covalent homodimers. As observed for other
      monothiol glutaredoxins, Trypanosoma brucei 1-C-Grx1 was not active in the
      glutaredoxin assay with hydroxyethyl disulfide and glutathione nor catalyzed the
      reduction of insulin disulfide. In addition, it lacked peroxidase activity and
      did not catalyze protein (de)glutathionylation. Upon oxidation, 1-C-Grx1 forms an
      intramolecular disulfide bridge and, to a minor degree, covalent dimers. Both
      disulfide forms are reduced by the parasite trypanothione/tryparedoxin system. 1
      C-Grx1 shows mitochondrial localization. The total cellular concentration is at
      least 5 microm. Thus, 1-C-Grx1 is an abundant protein especially in the
      rudimentary organelle of the mammalian form of the parasite. Expression of 1-C
      Grx1 in Grx5-deficient yeast cells with its authentic presequence targeted the
      protein to the mitochondria and partially restored the growth phenotype and
      aconitase activity of the mutant, and conferred resistance against hydroperoxides
      and diamide. The parasite Grx2 and 3 failed to substitute for Grx5. This is
      surprising because even bacterial and plant 1-Cys-glutaredoxins efficiently
      revert the defects, and may be due to the lack of two basic residues conserved in
      all but the trypanosomatid proteins.

PMID- 18095867
TI  - A new subfamily of bacterial glutamate/aspartate receptors.
AB  - The specificity of bacterial nutrient importers of the ATP-binding cassette (ABC)
      type depends on external receptor proteins that not only bind the solute to be
      transported, but also initiate the transport process by inducing ATP hydrolysis
      in the cytoplasmic nucleotide-binding domains. Here we propose a mode of ligand
      binding to the solute-binding protein AatJ that is required for glutamate uptake
      by the AatJMQP transporter in Pseudomonas putida KT2440. A homology model of the
      AatJ-glutamate complex was constructed using the E. coli glutamine-binding
      protein GlnH as the template. The general validity of the model was then
      confirmed by alanine scanning mutagenesis of several residues predicted to
      interact with the ligand and by semi-quantitative binding studies with [(14)C]
      Glu and [(14)C]-Asp. A database search indicated that AatJ is a member of a
      distinct subfamily of the family 3 solute-binding proteins with specificity
      towards glutamate and aspartate.

PMID- 18095868
TI  - Synthesis and characterization of a functional intact IgG in a prokaryotic cell
      free expression system.
AB  - Antibodies are an important component of the immune system of higher eukaryotes.
      Furthermore, they are effective tools in basic research, medical diagnostics and
      therapy. Recombinant expression of these heterotetrameric, disulfide-bridged
      proteins is usually performed in mammalian cells. Here, we describe the cell-free
      expression of a mouse monoclonal antibody, MAK33, in a coupled
      transcription/translation system, based on an Escherichia coli lysate. Both the
      heavy and the light chain can be produced efficiently in this setup. However,
      they fail to form functional antibodies. With a view to overcome folding and
      oxidation defects, we supplemented the system with the oxidoreductases PDI
      (protein disulfide isomerase) and DsbC and the ER-specific chaperones Grp94 and
      BiP; furthermore, we optimized the redox conditions. We found that functional
      antibodies can only be obtained in the presence of an oxidoreductase. In
      contrast, the addition of Grp94 and/or BiP had no influence on the productive
      folding reaction. The comparison of the antibody expressed in vitro with MAK33
      expressed in cell culture showed that the in vitro expressed antibody is
      correctly assembled, disulfide-bridged and shows identical antigen affinity. The
      stability of the in vitro expressed non-glycosylated IgG is comparable to that of
      the authentic antibody.

PMID- 18095869
TI  - Collagen IV regulates Caco-2 cell spreading and p130Cas phosphorylation by FAK
      dependent and FAK-independent pathways.
AB  - We previously observed that collagen IV regulates Caco-2 intestinal epithelial
      cell spreading and migration via Src-dependent p130(Cas) phosphorylation and
      stimulates focal adhesion kinase (FAK). However, the role of FAK and the related
      kinase, Pyk2, in Caco-2 spreading and migration is unclear. FAK- or Pyk2-specific
      siRNAs reduced protein levels by 90%. However, when detached cells were replated
      on collagen IV neither individual nor combined FAK and Pyk2 siRNAs affected the
      cell spreading rate. As combined FAK and Pyk2 siRNAs increased p130(Cas) protein
      levels, we cotransfected cells with 1 nm p130(Cas) siRNA to partially reduce
      p130(Cas) protein to control levels. Although p130(Cas) Tyr(P)(249)
      phosphorylation was reduced by 60%, cell spreading was unaffected. Combined siRNA
      reduction of FAK, Pyk2 and p130(Cas) increased cell spreading by 20% compared to
      p130(Cas) siRNA alone, suggesting that FAK and Pyk2 negatively regulate spreading
      in addition to stimulating spreading via p130(Cas). FAK-binding mutant SH3 domain
      deleted rat p130(Cas) was not phosphorylated after adhesion and, unlike full
      length p130(Cas), did not restore spreading after human-specific p130(Cas) siRNA
      knockdown of endogenous p130(Cas). Together, these data suggest that FAK
      positively regulates Caco-2 spreading on collagen IV via p130(Cas)
      phosphorylation, but also suggests that FAK may negatively regulate spreading
      through other mechanisms and the presence of additional FAK-independent pathways
      regulating p130(Cas).

PMID- 18095870
TI  - Differential effects of novel tumour-derived p53 mutations on the transformation
      of NIH-3T3 cells.
AB  - The p53 tumour suppressor gene is frequently mutated in human tumours and
      different tumour-derived mutations have varying effects on cells. The effect of a
      novel tumour-derived p53 mutation and two recently described mutations from South
      African breast cancer patients on the growth rate, colony formation, cell cycle
      arrest after irradiation and response to chemotherapeutic drugs was investigated.
      None of the p53 mutations had any significant effect on the inherent growth rate
      of the cells; however, contact inhibition of growth in two of the mutants was
      lost. These same two mutants formed colonies in soft agar, whereas the third
      mutant did not. All three of the mutants failed to show a G(1) cell cycle arrest
      after exposure to 7 Gy of [(60)Co] radiation, albeit to different degrees. Cells
      expressing the p53 mutants were either more sensitive to cisplatin and melphalan
      or more resistant than the untransfected cells, depending on the mutation.
      However, there was no difference in response to daunorubicin treatment. These
      results demonstrate that different p53 mutations exert varying biological effects
      on normal cells, with some altering checkpoint activation more effectively than
      others. The data also suggest that the nature of the p53 mutation influences the
      sensitivity to cytostatic drugs.

PMID- 18095871
TI  - Employing Rhodobacter sphaeroides to functionally express and purify human G
      protein-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) represent the largest class of cell surface
      receptors and play crucial roles in many cellular and physiological processes.
      Functional production of recombinant GPCRs is one of the main bottlenecks to
      obtaining structural information. Here, we report the use of a novel bacterial
      expression system based on the photosynthetic bacterium Rhodobacter sphaeroides
      for the production of human recombinant GPCRs. The advantage of employing R.
      sphaeroides as a host lies in the fact that it provides much more membrane
      surface per cell compared to other typical expression hosts. The system was
      tailored to overexpress recombinant receptors under the control of the moderately
      strong and highly regulated superoperonic photosynthetic promoter pufQ. We tested
      this system for the expression of some class A GPCRs, namely, the human adenosine
      A2a receptor (A2aR), the human angiotensin AT1a receptor (AT1aR) and the human
      bradykinin B2 receptor (B2R). Several different constructs were examined and
      functional production of the recombinant receptors was achieved. The best
      expressed receptor, AT1aR, was solubilized and affinity-purified. To the best of
      our knowledge, this is the first report of successful use of a bacterial host--R.
      sphaeroides--to produce functional recombinant GPCRs under the control of a
      photosynthetic gene promoter.

PMID- 18095872
TI  - Heparinase selectively sheds heparan sulphate from the endothelial glycocalyx.
AB  - A healthy vascular endothelium is coated by the endothelial glycocalyx. Its main
      constituents are transmembrane syndecans and bound heparan sulphates. This
      structure maintains the physiological endothelial permeability barrier and
      prevents leukocyte and platelet adhesion, thereby mitigating inflammation and
      tissue oedema. Heparinase, a bacterial analogue to heparanase, is known to attack
      the glycocalyx. However, the exact extent and specificity of degradation is
      unresolved. We show by electron microscopy, immunohistological staining and
      quantitative measurements of the constituent parts, that heparinase selectively
      sheds heparan sulphate from the glycocalyx, but not the syndecans.

PMID- 18095874
TI  - Cloning, expression and characterization of insulin-degrading enzyme from tomato
      (Solanum lycopersicum).
AB  - A cDNA encoding insulin-degrading enzyme (IDE) was cloned from tomato (Solanum
      lycopersicum) and expressed in Escherichia coli in N-terminal fusion with
      glutathione S-transferase. GST-SlIDE was characterized as a neutral thiol
      dependent metallopeptidase with insulinase activity: the recombinant enzyme
      cleaved the oxidized insulin B chain at eight peptide bonds, six of which are
      also targets of human IDE. Despite a certain preference for proline in the
      vicinity of the cleavage site, synthetic peptides were cleaved at apparently
      stochastic positions indicating that SlIDE, similar to IDEs from other organisms,
      does not recognize any particular amino acid motif in the primary structure of
      its substrates. Under steady-state conditions, an apparent K(m) of 62+/-7 microm
      and a catalytic efficiency (k(cat)/K(m)) of 62+/-15 mm(-1) s(-1) were determined
      for Abz-SKRDPPKMQTDLY(NO(3))-NH(2) as the substrate. GST-SlIDE was effectively
      inhibited by ATP at physiological concentrations, suggesting regulation of its
      activity in response to the energy status of the cell. While mammalian and plant
      IDEs share many of their biochemical properties, this similarity does not extend
      to their function in vivo, because insulin and the beta-amyloid peptide, well
      established substrates of mammalian IDEs, as well as insulin-related signaling
      appear to be absent from plant systems.

PMID- 18095873
TI  - Inhibition of human mu-calpain by conformationally constrained calpastatin
      peptides.
AB  - The 27-mer peptide CP1B-[1-27] derived from exon 1B of calpastatin stands out
      among the known inhibitors for mu- and m-calpain due to its high potency and
      selectivity. By systematical truncation, a 20-mer peptide, CP1B-[4-23], was
      identified as the core sequence required to maintain the affinity/selectivity
      profile of CP1B-[1-27]. Starting with this peptide, the turn-like region
      Glu(10)(i)-Leu(11)(i+1)-Gly(12)(i+2)-Lys(13)(i+3) was investigated. Sequence
      alignment of subdomains 1B, 2B, 3B and 4B from different mammalians revealed that
      the amino acid residues in position i+1 and i+2 are almost invariably flanked by
      oppositely charged residues, pointing towards a turn-like conformation stabilized
      by salt bridge/H-bond interaction. Accordingly, using different combinations of
      acidic and basic residues in position i and i+3, a series of conformationally
      constrained variants of CP1B-[4-23] were synthesized by macrolactamization
      utilizing the side chain functionalities of these residues. With the combination
      of Glu(i)/Dab(i+3), the maximum of conformational rigidity without substantial
      loss in affinity/selectivity was reached. These results clearly demonstrate that
      the linear peptide chain corresponding to subdomain 1B reverses its direction in
      the region Glu(10)-Lys(13) upon binding to mu-calpain, and thereby adopts a loop
      like rather than a tight turn conformation at this site.

PMID- 18095876
TI  - Adjuvant aromatase inhibitors and emerging quality-of-life considerations.

PMID- 18095875
TI  - RNA interference-mediated inhibition of Semliki Forest virus replication in
      mammalian cells.
AB  - RNA interference (RNAi) has recently shown promise as a mode of inhibition of
      slowly replicating viruses causing chronic diseases such as hepatitis C. To
      investigate whether RNAi is also feasible for rapidly growing RNA viruses such as
      alphaviruses, we tested the ability of expressed short hairpin RNAs (shRNAs) to
      inhibit the Semliki Forest virus (SFV), a rapidly replicating positive-strand RNA
      virus. Plasmids expressing shRNAs targeting SFV target sequences under the
      control of a human U6 promoter were introduced into BHK-21 cells. The targets
      included sequences encoding nonstructural (nsP1, 2, and 4) and structural
      (capsid) proteins as well as nonviral sequences serving as control targets.
      Twenty-four to 48 hours following transfection with shRNA plasmids, the cells
      were infected with replication-competent or replication-deficient recombinant SFV
      expressing green fluorescent protein (GFP) at a multiplicity of infection (MOI)
      of approximately 5. Viral replication was monitored by fluorescence microscopy
      and flow cytometry. Specific and marked reduction of viral replication was
      observed with shRNAs targeting nsP1 and nsP4. The degree of inhibition of the
      replication-deficient SFV was >or=70% over a 5-day period, a level similar to the
      transfection efficiency, suggesting complete inhibition of nonreplicating virus
      in the transfected cell population. However, only nsP1 shRNA was inhibitory
      against replication-competent SFV (approximately 30%-50% reduction), and this
      effect was transient. No inhibition was observed with control shRNAs. In contrast
      to the recent success of RNAi approaches for slowly growing viruses, these
      results illustrate the challenge of inhibiting very rapidly replicating RNA
      viruses by RNAi. However, the addition of RNAi approaches to other antiviral
      modalities might improve the response to acute infections.

PMID- 18095878
TI  - To switch or not to switch: should the updated Intergroup Exemestane Study alter
      our decision?
AB  - Adjuvant therapy for breast cancer with aromatase inhibitors improves survival
      compared with tamoxifen; however, whether they should be given upfront or
      sequentially after 2-3 years of tamoxifen in estrogen receptor-positive early
      breast cancer affecting postmenopausal women is unclear. The Intergroup
      Exemestane Study looked at 4724 postmenopausal patients with estrogen receptor
      positive or unknown breast cancer who had been disease free for 2-3 years on
      tamoxifen and were randomly assigned to switch to exemestane or to continue
      tamoxifen for the remainder of a 5-year endocrine treatment period. A significant
      disease-free survival advantage (p = 0.0001) was seen in favor of exemestane,
      with an absolute benefit of 3.3% by the end of treatment. This trial is the first
      to show an overall survival advantage for switching in estrogen receptor-positive
      breast cancer (p<or= 0.05). In total, 222 deaths occurred in the exemestane group
      compared with 261 deaths in the tamoxifen group, with a hazard ratio of 0.8 (95%
      confidence interval: 0.71-1.02; p = 0.08). A retrospective exclusion of patients
      who had estrogen receptor-negative disease improved the adjusted hazard ratio to
      0.85 (0.69-1.0; p = 0.05). Contralateral breast cancer was reduced by 50% both in
      intention-to-treat and estrogen receptor-positive groups. These results indicate
      that a similar overall reduction in recurrence can be achieved with a switching
      or an upfront aromatase inhibitor strategy, but with a reduction in the overall
      morbidity. The 5% of early breast cancer patients who relapse in the first 2
      years of tamoxifen treatment can be identified from 10% of the overall
      population. The remaining 90% could switch after 2-3 years. Controversy remains
      regarding whether switching is the optimal strategy and will only be resolved
      following the results of the Breast International Group 1-98 trial involving
      sequential therapy. Switching to exemestane for patients who have already had
      tamoxifen therapy for 2-3 years would appear to be an appropriate strategy for
      the majority of early breast cancer patients.

PMID- 18095879
TI  - Pure and robotic-assisted laparoscopic radical prostatectomy: technology and
      techniques merge to improve outcomes.
AB  - Laparoscopic radical prostatectomy is rapidly becoming the preferred approach in
      the surgical management of prostate cancer. The enhanced visibility provided to
      the surgeon by magnification allows for a better definition of anatomical
      landmarks, which were not apparent with open, nonmagnified surgery. Recent
      descriptions of the periprostatic anatomy, including the fascial layers
      surrounding the prostate, the structure of the neurovascular bundles and the
      components of the urethral sphincteric complex, allow the surgeon to refine
      available surgical techniques and create new ones with the goal of maximizing
      potency and continence preservation. The advent of the da Vinci robot to assist
      laparoscopic surgery served as a platform to enhance the surgeon' laparoscopic
      skills and to define further technological needs, such as better 3D vision
      systems and the development of hand-held articulating instruments that maintain
      haptic perception. This review summarizes the newer technologies available,
      recent anatomical descriptions of the periprostatic area and refinements in
      technique. The ultimate goal of the merge of technology with refinements in
      technique and a better anatomical understanding is to continue to improve the
      surgical outcomes with laparoscopy.

PMID- 18095880
TI  - Development of antiangiogenic agents for ovarian cancer.
AB  - Epithelial ovarian cancer (EOC) remains a major source of cancer morbidity and
      mortality, despite advances in surgical and chemotherapeutic management. The
      molecular pathways that control angiogenesis have been demonstrated to be key to
      the pathogenesis of EOC, and have been shown to have prognostic significance.
      Increased understanding of the pathways and molecules involved in angiogenesis
      has allowed the identification of a number of targets for antiangiogenic
      therapies and the development of a variety of antiangiogenic drugs. There is now
      significant preclinical evidence, and a growing body of clinical data,
      demonstrating promising results with antiangiogenic drugs in the treatment of
      EOC. Single-agent VEGF inhibitor response rates in pretreated patients of between
      15 and 20% have been reported, with much higher response rates when used in
      combination with chemotherapeutic agents. These benefits, however, must be
      balanced with the toxicities associated with these drugs, particularly the more
      serious ones, such as gastrointestinal perforation. The results of ongoing and
      future randomized clinical trials will confirm if, and how, antiangiogenic
      therapies should be integrated into the routine management of EOC. However,
      critical issues, such as the relative importance of combination remission
      induction regimens and maintenance therapy, remain poorly defined.

PMID- 18095881
TI  - ETS transcription factors: oncogenes and tumor suppressor genes as therapeutic
      targets for prostate cancer.
AB  - ETS factors represent one of the largest families of transcriptional regulators
      and have known functional roles in many biological processes. Significantly, ETS
      factors have oncogenic and suppressive activity and their aberrant expression is
      associated with many of the processes that lead to prostate cancer progression.
      The targeting of transcription for therapeutic gain has met with some success.
      Therefore, better understanding the mechanisms that regulate ETS factor activity
      during both normal and aberrant transcription provides a novel means to identify
      processes that may be targeted in order to re-establish the normal ETS regulatory
      networks that are perturbed in cancer. Specific examples of altered ETS factor
      expression are highlighted, and therapeutic technologies that may be used to
      target ETS factors and their cofactors and downstream target genes in prostate
      cancer are discussed.

PMID- 18095882
TI  - Diet and prostate cancer risk reduction.
AB  - Prostate cancer is the most commonly diagnosed malignancy in males. The current
      body of literature supports the role of nutritional products in the reduction of
      prostate cancer. This review critically addresses the natural products with the
      greatest potential to reduce the risk of prostate cancer, including lycopene,
      vitamin E, selenium, vitamin D, soy and green tea. The toxicities of the dietary
      products are addressed. The direction of future studies lies in clarifying the
      effects of these products and exploring the biological mechanisms responsible for
      the prevention of prostate cancer.

PMID- 18095883
TI  - Current optimal chemotherapy for advanced urothelial cancer.
AB  - Conventional frontline cisplatin-based combination chemotherapy with gemcitabine
      and cisplatin, or traditional or dose-dense methotrexate, vinblastine,
      doxorubicin and cisplatin, yields high response rates but few durable remissions
      for advanced urothelial cancer. Salvage therapy is generally disappointing with
      few responses. A significant proportion of patients exhibit renal dysfunction,
      entailing carboplatin-based regimens that appear inferior to cisplatin-based
      regimens, which warrants a special focus In this population. The profusion of
      novel biologic agents offers the promise of improved outcomes. A
      multidisciplinary approach is necessary to make therapeutic advances.

PMID- 18095885
TI  - Bladder cancer following upper tract urothelial carcinoma.
AB  - Upper tract urothelial carcinoma (UTUC) is uncommon relative to primary bladder
      transitional cell carcinoma, with notable differences at the genetic, molecular
      and clinical levels. A variety of management options with similar oncologic
      outcomes are available for UTUC. Regardless of upper tract treatment modality,
      recurrence in the bladder consistently occurs in 20-50% of patients, thus
      presenting a significant clinical challenge. The initial intravesical relapse
      typically occurs within the first 2 years following upper tract therapy, but the
      risk is lifelong and repeat episodes are common. The identification of variables
      that allow accurate risk stratification of UTUC patients with regards to future
      bladder relapse is crucial. Unfortunately, to date, no variables have been
      identified that can reliably predict such bladder recurrences. A history of
      bladder cancer prior to UTUC resection and upper tract tumor multifocality are
      frequently reported clinical risk factors. Candidate molecular markers, such as E
      cadherin, also hold promise for improving patient risk stratification. The impact
      of bladder recurrences on patient survival is still poorly defined. The risk of
      progression to invasive bladder disease is not well documented but appears to be
      an infrequent event. This article highlights important recent observations and
      key current issues regarding UTUC and subsequent bladder cancer. In addition, we
      suggest a bladder surveillance regimen following UTUC and provide recommendations
      for managing patients with intravesical recurrences.

PMID- 18095884
TI  - VHL inactivation in renal cell carcinoma: implications for diagnosis, prognosis
      and treatment.
AB  - Clear cell renal cell carcinoma (ccRCC) provides a tumor paradigm for the
      integration of genetics, molecular biology, therapeutic target validation and the
      introduction of high-impact treatment strategies. Most cases of sporadic as well
      as familial ccRCC acquire somatic inactivating mutations of the von Hippel-Lindau
      tumor-suppressor gene, VHL. pVHL, VHL gene product and a protein member of the E3
      ubiquitin ligase family, acts in normal cells to direct the degradation and
      clearance of the hypoxia inducible factor (HIF)alpha transcription factor family,
      such that in its absence, as in ccRCC, the HIF proteins stabilize, accumulate to
      supraphysiologic levels and activate the transcription of genes such as VEGF and
      PDGF, which contributes substantially to the physiology of the tumor, and has
      been assessed indirectly as a prognostic factor. Molecularly targeted therapy
      blocking components of this pathway has been successfully introduced to the
      clinic with a substantive impact on clinical parameters of RCC. This review will
      examine the regulation of these molecular pathways in RCC and discuss the impact
      on the clinical management of patients with RCC.

PMID- 18095886
TI  - Stereotactic body radiation therapy for early-stage non-small-cell lung cancer.
AB  - Stereotactic body radiation therapy has emerged as a novel oncologic therapy and
      experience with the use of stereotactic body radiation therapy for the treatment
      of early-stage non-small-cell lung cancer has grown over the last 10 years. This
      article reviews the radiobiologic, physical/technical and clinical aspects of
      stereotactic body radiation therapy for early-stage non-small-cell lung cancer.
      The literature is also reviewed.

PMID- 18095887
TI  - Targeted therapy in chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is characterized by the formation of the
      Philadelphia chromosome and oncogenic signaling by the resulting Bcr-Abl fusion
      protein. Understanding the molecular basis of CML has led to the development of
      highly effective targeted therapies that block Bcr-Abl tyrosine kinase activity.
      Imatinib, the current first-line therapy for CML, induces durable treatment
      responses in most patients. However, patients may develop imatinib resistance,
      which is often due to BCR-ABL mutations. With the availability of second
      generation tyrosine kinase inhibitors, an effective therapeutic option other than
      stem cell transplantation is available following imatinib failure. Randomized
      trial data suggest that dasatinib treatment is superior to imatinib dose
      escalation in patients with imatinib resistance. Nilotinib, a recently approved
      analogue of imatinib, has also demonstrated encouraging treatment responses in
      patients with imatinib-resistant CML. Other agents (including bosutinib and INNO
      406) are in clinical development. With the potential availability of multiple
      treatment options for patients with CML, it may be possible to tailor treatment
      according to individual patient or disease characteristics, for example, BCR-ABL
      mutations. Future CML treatment may involve combination strategies. Overall,
      targeted agents have significantly improved the prognosis of patients diagnosed
      with CML.

PMID- 18095888
TI  - Advances in minimally invasive surgery in the treatment of colorectal cancer.
AB  - Colorectal cancer (CRC) is the second leading cause of cancer-related death in
      the USA. Surgery is the primary treatment for most patients with CRC. Over the
      past 15 years, minimally invasive techniques for colorectal surgery have been
      developed. There is growing evidence that these techniques have significant
      advantages in short-term outcomes (e.g., postoperative pain and length of
      hospital stay) with similar long-term recurrence and overall survival. While
      transanal local excision has been shown to be inferior to radical resection for
      early rectal cancer, transanal endoscopic microsurgery (TEM) is a minimally
      invasive technique that appears to facilitate local excision in appropriate
      patients. TEM combined with radiotherapy has demonstrated promising early results
      and is currently being investigated in clinical trials as a potential alternative
      to radical surgery. We summarize the current literature on these minimally
      invasive approaches to CRC.

PMID- 18095889
TI  - Palliative treatment of poor prognosis patients with malignant gliomas.
AB  - High-grade gliomas are the most commonly diagnosed malignant brain tumor in
      adults. Prognosis can be estimated by examining risk factors, including
      histology, age and performance status. Postoperative radiation therapy is
      associated with improved survival and standard treatment includes external beam
      radiotherapy to a dose of 60 Gy in 30-33 fractions. Patients with poor prognostic
      features have a more limited benefit from radiotherapy. This article reviews the
      current state of knowledge on risk stratification and analyzes strategies that
      can be employed to better individualize treatment for poor-prognosis patients.

PMID- 18095890
TI  - Neuronavigation in neurosurgery: current state of affairs.

PMID- 18095891
TI  - Pulmonary Drug Delivery System for inhalation therapy in mechanically ventilated
      patients.
AB  - The Pulmonary Drug Delivery System (PDDS) Clinical represents a newer generation
      of electronic nebulizers that employ a vibrating mesh or aperture plate to
      generate an aerosol. The PDDS Clinical is designed for aerosol therapy in
      patients receiving mechanical ventilation. The components of the device include a
      control module that is connected to the nebulizer/reservoir unit by a cable. The
      nebulizer contains Aerogen's OnQ aerosol generator. A pressure sensor monitors
      the pressure in the inspiratory limb of the ventilator circuit and provides
      feedback to the control module. Based on the feedback from the pressure sensor,
      aerosol generation occurs only during a specific part of the respiratory cycle.
      In bench models, the PDDS Clinical has high efficiency for aerosol delivery both
      on and off the ventilator, with a lower respiratory tract delivery of 50-70% of
      the nominal dose. Currently, the PDDS Clinical is being evaluated for the
      treatment of ventilator-associated pneumonia with aerosolized amikacin, an
      aminoglycoside antibiotic. Preliminary studies in patients with ventilator
      associated pneumonia found that the administration of amikacin via PDDS reduced
      the need for concomitant intravenous antibiotics; however, more definitive
      clinical studies are needed. The PDDS Clinical delivers a high percentage of the
      nominal dose to the lower respiratory tract, and is well suited for inhalation
      therapy in mechanically ventilated patients.

PMID- 18095892
TI  - Embolic protection: the FilterWire EZ Embolic Protection System.
AB  - The field of interventional cardiology has grown dramatically over the past 30
      years, including recent advances in the area of peripheral vascular intervention.
      The phenomenon of no-reflow, characterized by a reduction in coronary blood flow
      during vascular intervention, has been associated with adverse outcomes in both
      saphenous vein graft and carotid artery interventions. Distal embolic protection
      devices, such as the FilterWire EZ System, have been shown to reduce the
      incidence of no-reflow and adverse cardiac events in patients undergoing
      saphenous vein graft interventions. Recently approved indications for the
      FilterWire EZ System include carotid artery stenting. With the definite reduction
      in adverse events from the use of distal protection, future advancements will
      focus on improved deliverability of such devices.

PMID- 18095893
TI  - The Amplatzer Septal Occluder, a transcatheter device for atrial septal defect
      closure.
AB  - Transcatheter device closure of secundum atrial septal defect (ASD) has been
      widely accepted and is becoming the standard treatment of this malformation.
      Among the devices used for transcatheter closure, the Amplatzer Septal Occluder
      is the first device to receive full approval from the US FDA for clinical use in
      patients with secundum ASD. It is safe, user-friendly and effective in closing a
      wide range of sizes of secundum ASD and has arguably become the most popular
      device in the world.

PMID- 18095894
TI  - Rheos Baroreflex Hypertension Therapy System to treat resistant hypertension.
AB  - Resistant hypertension has a high prevalence and is associated with high
      morbidity and mortality. The Rheos Baroreflex Hypertension Therapy System is an
      implantable device that offers a completely new approach to treating patients
      with resistant hypertension by electrically activating the carotid baroreflex.
      Preliminary results from current feasibility clinical trials have shown sustained
      decreases in blood pressure after 1 year. The pivotal trial for US FDA approval
      and market release is currently ongoing. This article profiles the Rheos System
      and evaluates the treatment of resistant hypertension in general.

PMID- 18095895
TI  - US FDA perspective on the regulations of medical-grade polymers: cyanoacrylate
      polymer medical device tissue adhesives.
AB  - This article provides a brief description of the uses and clinical applications
      of medical-grade polymers, in particular synthetic cyanoacrylate adhesive/glue
      devices that have been cleared and/or approved as medical devices by the US FDA
      since the Medical Device Amendments of 1976 were enacted. This includes Class I
      cyanoacrylate devices (e.g., liquid bandages), Class II cyanoacrylate devices
      (e.g., dental cements), and Class III (premarket approval) cyanoacrylate devices
      such as Dermabond, Indermil Tissue Adhesive, Histoacryl and Histoacryl Blue
      Topical Skin Adhesive, and Trufill n-Butyl Cyanoacrylate Embolic Agent. By citing
      an example of FDA approved Class III devices in the cyanoacrylate technology, the
      article provides a brief discussion of the FDA approval process of medical
      devices. It includes the FDA issues regarding the published guidance document for
      'Cyanoacrylate Topical Tissue Adhesives' that will provide guidance to regulatory
      personnel and manufacturers in the preparation of investigational device
      exception applications and in the development of valid scientific evidence to
      support premarket approval applications for cyanocrylate tissue adhesives
      intended for topical approximation of skin and others. The article provides a
      short regulatory description of the US FDA; under what laws its operates, how the
      FDA evaluates new devices for marketing, and how the device regulatory system
      works, for example, Class I, Class II, and Class III cyanoacrylate medical
      devices.

PMID- 18095896
TI  - Cardiac device testing enhanced by simultaneous imaging modalities: the Visible
      Heart, fluoroscopy and echocardiography.
AB  - The evaluation of implantable cardiac devices requires innovative and critical
      testing in all phases of the design process. The recent development of an in
      vitro isolated heart model, the Visible Heart, allows for novel examination of
      device-tissue interactions to evaluate device placement and performance within a
      functioning heart. This model provides product designers with a rapid method to
      critically assess prototypes, thus expediting design decisions. The future of
      cardiac devices will include beating heart procedures (e.g., transcatheter
      delivered valves), and such implantations will probably utilize simultaneous
      multiple imaging modalities. These imaging modes allow for verification of proper
      device positioning, refinement of device/deployment procedures, and eventual
      evaluation of resultant cardiac function within experimental and clinical
      settings.

PMID- 18095897
TI  - Robotic pediatric urology.
AB  - The number of current advances in robotic surgery for the pediatric population is
      growing every day: the different procedures range from extirpative to
      reconstructive, including pyeloplasty, reimplantation, catheterizable channels
      and augmentation. Despite its early success, robotic surgery still poses many
      challenges in pediatric patients. Robotics also allows the seasoned laparoscopist
      to become more proficient and refined, providing a greater armamentarium to
      expand minimally invasive surgery to more complex reconstructive procedures. The
      procedure most performed with the da Vinci Surgical System in pediatric urology
      is pyeloplasty for ureteropelvic junction obstruction. There are many other
      procedures that can be performed with the robot, such as ureteral reimplantation,
      and nephrectomy, both total and partial. The reconstructive aspect has been taken
      to the next level where more difficult procedures, such as appendicovesicostomy
      and bladder augmentation, can be performed in children.

PMID- 18095898
TI  - Role of pre- and intraoperative imaging and neuronavigation in neurosurgery.
AB  - Advances in neuroimaging acquisition, computing and image processing have enabled
      neurosurgeons to use radiological imaging to guide both preoperative planning and
      intraoperative guidance. In preoperative planning, imaging may be used to
      evaluate surgical risks, choose the best method of intervention and select the
      safest surgical approach. Neuronavigation may be useful in designing the surgical
      flap and alerting the surgeon of surrounding anatomy. Finally, intraoperative
      imaging may be used to define brain shift associated with the resection of
      intracranial lesions, assist in more complete lesion resection, and monitor for
      certain intraoperative complications. In the following review, we briefly examine
      the history of neuroradiology for neurosurgery, neuronavigation and
      intraoperative imaging and trace their advances to current systems in use. We
      will also highlight new experimental applications of neuroimaging that are
      currently being refined.

PMID- 18095899
TI  - Evidence supporting the use of bone morphogenetic proteins for spinal fusion
      surgery.
AB  - Bone morphogenetic proteins (BMPs) are capable of promoting bone healing and even
      induce de novo osteogenesis. Their clinical application in spinal fusion surgery
      has recently increased in popularity. This is especially true for the use of BMPs
      in combination with artificial bone substitutes that have the capability to
      replace autologous bone graft, which can be associated with severe harvesting
      complications. This review will examine the use of BMP-2 and BMP-7 as
      commercially available products that have proven their osteoinductive capacity in
      spinal fusion. We will perform an overview of the literature for scientific
      evidence supporting the use of these new technologies. Despite their high
      osteoinductive potency, the use of BMPs does not replace proper surgical
      stabilization in spinal fusion. Safety issues with BMPs are osteoclast
      activation, postoperative swelling and hyperostosis. Despite these issues,
      manufacturers continue to expend more effort concerning proper application,
      dosage and carriers for these devices for spinal fusion, both presently and in
      the future.

PMID- 18095900
TI  - Shortening hospital stay for thyroid surgery.
AB  - The number of outpatient surgical procedures performed in hospitals, increases
      daily. In some countries, such as Italy, outpatient operations outnumber
      inpatient operations. The incidence of thyroid disorders and, in particular, the
      cancer forms, has been increasing sharply for many years in several countries.
      Even if thyroid surgery is performed with low morbidity, no mortality and short
      operation time, some potentially lethal complications are strong arguments
      against shortening of hospital stay. The purpose of this review is to examine the
      relevant updated published results on the outcome measures that can be used to
      assess the quality of shortstay surgery for thyroid disease with well-controlled
      trials. We discuss the special ethical and legal issues that this thyroid surgery
      raises. Searches were last updated in May 2007.

PMID- 18095901
TI  - Investigational methods and radiological therapeutic approaches.

PMID- 18095903
TI  - Metabolic efficiency with ranolazine for less ischemia in non-ST elevation acute
      coronary syndromes (MERLIN TIMI-36) study.
AB  - Ranolazine is a piperazine derivative believed to reduce anginal symptoms by
      preventing ischemia-mediated sodium and calcium overload in myocardial cells
      through inhibition of the late sodium current (late INa). Three small studies
      demonstrated the antianginal efficacy of ranolazine alone and in combination with
      betablockers or calcium channel blockers on conventional end points such as total
      exercise duration and time to ischemia/angina on a treadmill; however, questions
      of safety related to QT prolongation, efficacy in women and potential utility in
      higher risk populations remained. Metabolic Efficiency with Ranolazine for Less
      Ischemia in Non-ST Elevation Acute Coronary Syndromes-Thrombolysis in Myocardial
      Infarction (MERLIN-TIMI) 36 was a large randomized, double-blind, placebo
      controlled trial, which evaluated the efficacy and safety of ranolazine initiated
      acutely and continued as chronic therapy following a non-ST-segment elevation
      acute coronary syndrome event. A total of 6560 patients were randomized 1:1 to
      ranolazine or placebo; the primary efficacy end point of the trial was a
      composite of cardiovascular death, myocardial infarction or recurrent ischemia.
      The key safety end points were death from any cause and symptomatic documented
      arrhythmia. Although statistically significant differences between the ranolazine
      and placebo groups were not reached in the primary efficacy analysis or in the
      major secondary outcome end point analyses (cardiovascular death, myocardial
      infarction or severe recurrent ischemia), the individual component of recurrent
      ischemia was significantly reduced by ranolazine, and ranolazine was demonstrated
      to be safe.

PMID- 18095905
TI  - Applications and software techniques for integrated cardiac multimodality
      imaging.
AB  - Several imaging technologies are available for diagnostic cardiac imaging, such
      as coronary computed tomography angiography (CTA), single photon emission
      computed tomography (SPECT) positron emission tomography (PET) and magnetic
      resonance imaging (MRI). Each of these techniques offers unique advantages, but
      also suffers from specific limitations. Software techniques are being developed
      to combine cardiac images from different modalities and generate composite
      multimodality images, allowing better diagnosis than that possible from images
      analyzed separately. Hybrid scanners (SPECT/CT and PET/CT) have also been
      proposed for integrated cardiac imaging. Physicians are presented with integrated
      fused images that contain complementary information from separate scans
      containing physiological and anatomical information. In this review, we present
      the latest approaches for integration of cardiac images from multiple modalities.

PMID- 18095904
TI  - Ezetimibe plus simvastatin cardiovascular outcomes study program.
AB  - Ezetimibe is a drug that impairs intestinal cholesterol absorption and decreases
      blood cholesterol levels. It has been shown that added to statins it can achieve
      a further reduction of low-density lipoprotein-cholesterol of 18-20%, overcoming
      the increase in absorption that follow the reduction in cholesterol synthesis by
      statins. Four major outcome trials are underway to study the effect of ezetimibe
      plus simvastatin in different subsets of high-risk patients: familiar
      hypercholesterolemia, degenerative aortic stenosis, chronic kidney disease and
      acute coronary syndrome. Hopefully, in the next few years the information
      provided by these trials will allow us to further reduce the increasing burden of
      cardiovascular disease.

PMID- 18095906
TI  - Cost-effective applications of cardiac computed tomography in coronary artery
      disease.
AB  - Computed tomography has been introduced as a noninvasive imaging modality used
      for coronary artery calcium scoring in asymptomatic individuals and contrast
      enhanced coronary angiography in symptomatic individuals. As the rising costs of
      healthcare reflect, in part, the development of these types of new expensive
      technologies for cardiac diagnosis, the economic considerations that surround
      them should be of interest to clinicians and payers alike. In this review, we
      discuss basic principles underlying economic efficiency analyses of medical
      products, using computed tomography in coronary artery disease as a case in
      point.

PMID- 18095907
TI  - Outpatient management of oral vitamin K antagonist therapy: defining and
      measuring high-quality management.
AB  - Oral anticoagulation therapy with warfarin is the mainstay of prevention and
      treatment of thromboembolic disease. However, it remains one of the leading
      causes of harmful medication errors and medication-related adverse events. The
      beneficial outcomes of oral anticoagulation therapy are directly dependent upon
      the quality of dose and anticoagulation management, but the literature is not
      robust with regards to what constitutes such management. This review focuses on,
      and attempts to define, the parameters of high-quality anticoagulation management
      and identifies the appropriate outcome measures constituting high-quality
      management. Elements discussed include the most fundamental measure, time in
      therapeutic range, along with other parameters including therapy initiation, time
      to therapeutic range, dosing management when patients are not in therapeutic
      range, perioperative dosing management, patient education, and other important
      outcome measures. Healthcare providers who manage oral anticoagulation therapy
      should utilize these parameters as a measure of their performance in an effort to
      achieve high-quality anticoagulation management.

PMID- 18095908
TI  - New insights and therapeutics for immune-mediated thrombocytopenia.
AB  - In recent years, great advances have been made in elucidating the pathogenesis of
      thrombocytopenia and the mechanisms of thrombopoiesis. Drawing upon decades of
      basic science and clinical research, the pathways behind the immune-mediated
      destruction of platelets have opened new avenues. This has led to the application
      of safer and more efficacious immunosuppressive agents, such as the anti-CD20
      monoclonal antibody rituximab, or potentially altering the co-stimulatory
      pathways of the immune system with an anti-CD40L (CD154) monoclonal antibody.
      This has been coupled with the discoveries of the genetic and molecular pathways
      in thrombopoiesis, including the identification and cloning of thrombopoietin
      (TPO) and its receptor. The use of recombinant TPO, such as PEG-rHuMGDF and
      rhTPO, to treat thrombocytopenia have paved the way for alternative peptidyl and
      nonpeptidyl thrombopoietic agents that are considered to be nonimmunogenic. Those
      that have undergone evaluation in humans include the Amgen megakaryopoiesis
      protein (AMG) 531 compound, eltrombopag, and AKR-501. Additional TPO mimetics
      show promise in vitro and await future development.

PMID- 18095909
TI  - Diagnosis and treatment of left-sided prosthetic valve thrombosis.
AB  - Left-sided prosthetic valve thrombosis is a life-threatening complication of the
      mechanical valves. Prosthetic valve thrombosis has been divided into obstructive
      forms (OPVT) and nonobstructive forms (NOPVT). Clinical presentation of OPVT is
      heart failure and systemic embolism of OPVT and NOPVT, but it may be
      asymptomatic. Transesophageal echocardiography is the technique of choice for
      diagnosis and treatment guidance. There are three treatment options. Surgery
      carries a high hospital mortality risk in severely sick patients. Thrombolysis
      has been successful in 80%, with a mortality of 4%, depending on obstruction and
      functional class. Embolic complications were 8-10% depending on obstruction, but
      not on thrombus size. Heparin treatment has been successful only in NOPVT, if
      thrombus diameter of less than 5 mm. Based on the latest evidence, thrombolysis
      should be first-line therapy if there are no contraindications, regardless of
      obstruction and functional class, if thrombus diameter is greater than, or equal
      to, 5 mm.

PMID- 18095910
TI  - The need for wider and appropriate utilization of aspirin and statins in the
      treatment and prevention of cardiovascular disease.
AB  - There is an increasing burden of occlusive cardiovascular disease (CVD) in
      developed, as well as in developing, countries. In fact, the WHO has projected
      that CVD will become the leading cause of death in the world in the next 10
      years. The proximate cause of virtually all occlusive vascular events is
      thrombosis and the principal underlying cause is atherosclerosis. Aspirin, which
      inhibits platelet-dependent cyclooxygenase for the entire life of the platelet,
      has clinically important antithrombotic effects. Statins, which principally
      decrease low-density lipoprotein cholesterol, triglycerides and increase high
      density lipoprotein cholesterol, have clinically important antiatherogenic
      effects. In secondary prevention, in a wide range of patients who have survived a
      prior myocardial infarction (MI), occlusive stroke, transient ischemic attack, as
      well as other high-risk conditions, long-term use of aspirin confers
      statistically significant and clinically important reductions in MI, stroke and
      CVD death. In addition, aspirin confers similar benefits when administered during
      acute MI or acute occlusive stroke. In primary prevention, aspirin confers a
      statistically significant and clinically important reduction in risk of a first
      MI but the data on stroke and CVD death remain inconclusive, so aspirin should be
      prescribed on an individual basis by the healthcare provider who weighs this
      clear benefit against long-term side effects. In a meta-analysis of 14 randomized
      trials of 90,056 subjects treated for 5 years, statins confer statistically
      significant and clinically important reductions in MI, stroke, CVD death and
      total mortality. In a meta-analysis of randomized trials of statins, in which
      aspirin was used in varying frequencies, the combination of aspirin and statins
      conferred greater clinical benefits than either agent alone on MI, occlusive
      stroke and CVD death. At present, the wider and more appropriate use of aspirin
      and statins will reduce premature MI, stroke and CVD death.

PMID- 18095911
TI  - Early detection and significance of structural cardiovascular abnormalities in
      patients with Type 2 diabetes mellitus.
AB  - Cardiovascular disease is the leading cause of death among patients with Type 2
      diabetes mellitus. The main forms of structural heart disease associated with
      diabetes are coronary heart disease and diabetic cardiomyopathy, which is
      characterized by left ventricular hypertrophy, left ventricular diastolic and
      systolic dysfunction. Asymptomatic structural heart disease is common and
      associated with a poor prognosis in patients with diabetes. Contemporary practice
      guidelines do not recommend screening of asymptomatic individuals for structural
      heart disease. Potential screening modalities, such as echocardiography, are
      costly and inaccessible. A simple, inexpensive blood test for brain natriuretic
      peptide is a useful marker of structural heart disease and is a prime candidate
      for screening patients with Type 2 diabetes mellitus and prioritizing referral
      for echocardiography.

PMID- 18095912
TI  - Diabetes and vascular disease.
AB  - Type 2 diabetes has reached epidemic proportions and is now recognized as a
      coronary heart disease equivalent. While the most common metabolic abnormality
      associated with diabetes is hyperglycemia, there are also abnormalities in
      carbohydrate, fat and protein metabolism. These abnormalities increase oxidative
      stress and activate the renin-angiotensin system leading to endothelial
      dysfunction and, thereafter, to systemic atherosclerosis. This systemic
      atherosclerosis is responsible for the increased cardiovascular morbidity and
      mortality related to diabetes. In this article, we review the evidence and
      discuss the rationale for comprehensive risk reduction to prevent and treat
      vascular disease in individuals with diabetes mellitus. The components of
      comprehensive risk reduction strategy consist of lifestyle changes, glycemic
      control, control of dyslipidemia and hypertension.

PMID- 18095914
TI  - An update on drug combinations for treatment of myeloma.
AB  - Multiple myeloma is the second most common haematological malignancy. It is
      becoming increasingly manageable with conventional and high-dose chemotherapy but
      there remains a critical need to develop both new drugs and combinations to
      improve long-term outcomes. Novel biological therapies that specifically target
      myeloma cells and/or their microenvironmental interactions are being developed
      that are highly effective, both as single agents and as combinations. Chief among
      these new agents are the proteasome inhibitor, bortezomib, and the
      immunomodulatory agents, thalidomide and lenalidomide. These drugs show improved
      single agent activity that is enhanced in combination. However, many drugs that
      are being developed in this setting may only have limited single agent activity,
      but combination use with these and other agents represents a very exciting way of
      targeting important pathogenic pathways crucial in myeloma development. This
      represents a challenge for both drug development and clinical trial evaluation,
      which has the potential to revolutionise the clinical management of myeloma and a
      paradigm for drug development in other diseases.

PMID- 18095915
TI  - Novel therapeutic strategies in development for prostate cancer.
AB  - Relatively few therapy options exist for patients with prostate cancer that has
      become resistant to androgen-deprivation therapy and has metastasized to distant
      sites. Survival for such patients is poor with a median survival of approximately
      20 months from the time of initiation of standard docetaxel-based chemotherapy.
      Promising new treatments are needed, and several are currently being evaluated,
      including those that target the hormonal axis, such as abiraterone,
      chemotherapies, such as satraplatin and ixabepilone, combinations of chemotherapy
      with other agents, such as bevacizumab and calcitriol, as well as a variety of
      immunotherapeutic approaches. This review will highlight recent and current
      studies for many of the promising developments for advanced disease, as well as
      novel early stage approaches.

PMID- 18095916
TI  - The potential of DMXAA (ASA404) in combination with docetaxel in advanced
      prostate cancer.
AB  - 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) is a vascular disrupting agent that
      has demonstrated efficacy in combination with taxane-based chemotherapy in
      patients with advanced cancer. Complementary modes of action, a lack of
      pharmacokinetic interaction and distinct adverse effect profiles provide a strong
      rationale for combining these anticancer agents. In a Phase II trial in men with
      hormone refractory prostate cancer, DMXAA (ASA404) in combination with docetaxel
      achieved a prostate-specific antigen response in more patients than docetaxel
      therapy alone, and was generally well tolerated. Further clinical evaluation of
      this combination in this patient population is warranted.

PMID- 18095917
TI  - Systemic lupus erythematosus: pharmacological developments and recommendations
      for a therapeutic strategy.
AB  - The management of systemic lupus erythematosus (SLE) has improved thanks to a
      better understanding of the immunopathogenesis of the disease and important
      advances in drug development. In contrast to the worrying paucity of new
      therapies for SLE at the end of the last century, several agents have emerged as
      useful treatments for this condition in the last decade. The efficacy of
      mycophenolate mofetil in the treatment of patients with lupus nephritis has been
      recently established in several clinical trials. There are increasing data from
      open-label studies to support the belief that B-cell depletion using the chimeric
      antibody rituximab is useful in the treatment of SLE. However, larger double
      blind clinical trials to confirm this belief are awaited. Other specific targeted
      therapeutic agents that act by inducing B-cell depletion, inhibiting co
      stimulatory molecules necessary for T-cell activation, tolerising B and T cells,
      blocking pro-inflammatory cytokines or complement and immunoablation are exciting
      advances in the race towards improving the outcome for patients with SLE.

PMID- 18095918
TI  - Therapeutic applications of aptamers.
AB  - Aptamers constitute a new class of oligonucleotides that have gained therapeutic
      importance. With the approval of the first aptamer drug, pegaptanib, interest in
      this class of oligonucleotides, often referred to as 'chemical antibodies', has
      increased. This article discusses aptamers in relation to other oligonucleotide
      molecules such as antisense nucleotides, short inhibitory sequences, ribozymes
      and so on. The development of pegaptanib is looked at from the point of view of
      the challenges faced in converting aptamers into therapeutic molecules. Cases of
      other aptamers, which show promise as drugs, are discussed in slightly greater
      detail. Comparison with antibodies and small molecules, which have hitherto held
      monopoly in this area, is also made.

PMID- 18095919
TI  - Iloperidone: a new benzisoxazole atypical antipsychotic drug. Is it novel enough
      to impact the crowded atypical antipsychotic market?
AB  - Iloperidone is a new-generation atypical antipsychotic agent, acting as a
      serotonin/dopamine (5-HT(2A)/D(2)) antagonist, under development by Vanda
      Pharmaceuticals for the treatment of schizophrenia, bipolar disorder and other
      psychiatric conditions. Chemically, iloperidone is a benzisoxazole, like
      risperidone, and shows a multiple receptor binding profile, sharing this feature
      with the other atypical antipsychotic agents. Administered orally, the drug is
      highly bound to plasma proteins and extensively metabolised. Several clinical
      trials have been carried out, to check efficacy, safety and side effects. In
      order to introduce iloperidone as an agent for the treatment of schizophrenia, a
      short overview of the disease and of the most important antipsychotic drugs
      available or under development will be reported. Iloperidone pharmacokinetics and
      pharmacodynamics are presented herein, together with an evaluation of clinical
      safety and efficacy results.

PMID- 18095920
TI  - An expert opinion on methylphenidate treatment for attention deficit
      hyperactivity disorder in pediatric patients with epilepsy.
AB  - Methylphenidate (MPH) is one of the most commonly prescribed medications to treat
      attention deficit hyperactivity disorder (ADHD). Despite the elevated rates of
      ADHD in children with epilepsy, few studies have examined the use of MPH in this
      population. Case reports have warned about new-onset seizures in patients treated
      with MPH, and drug-drug interactions between MPH and antiepileptic drugs (AEDs),
      as well as antidepressants. However, retrospective chart reviews, open-label
      trials and controlled trials of MPH in patients with epilepsy and ADHD have noted
      significant improvements in ADHD symptoms without an exacerbation of seizures or
      an adverse effect on AED serum levels. This paper reviews the chemistry and
      mechanisms of action of MPH, as well as preclinical, premarketing clinical trials
      and postmarketing data relevant to its use in patients with ADHD and epilepsy.

PMID- 18095921
TI  - Oral nabilone capsules in the treatment of chemotherapy-induced nausea and
      vomiting and pain.
AB  - BACKGROUND: Nabilone has been approved to treat chemotherapy-induced nausea and
      vomiting. Recent studies have explored cannabinoids in pain management.
      OBJECTIVES: To review the evidence for the use of cannabinoids in general and
      nabilone in particular; i) in managing chemotherapy-induced nausea and vomiting;
      and ii) in treating pain. METHOD: A systematic review of published English
      literature used the terms: cancer, cannabinoid, nabilone, nausea, pain,
      tetrahydrocannabinol and vomiting as search terms. Reviews, meta-analyses and
      treatment trials were reviewed. RESULTS/CONCLUSIONS: Nabilone is superior to
      placebo, domperidone and prochlorperazine but not metoclopramide or
      chlorpromazine. Cannabinoids do not add to benefits of 5-HT(3) receptor
      antagonists. Side effects are greater for nabilone than for prochlorperazine, in
      most studies patients prefered nabilone over prochlorperazine. Nabilone is
      ineffective in acute pain but benefits in neuropathic pain and central
      hypersensitization. Recent guidelines place nabilone as a second to fourth line
      drug for neuropathic pain.

PMID- 18095922
TI  - Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV
      infection.
AB  - Integrase is essential for HIV-1 replication; however, potent inhibition of the
      isolated enzyme in biochemical assays has not readily translated into antiviral
      activity in a manner consistent with inhibition of integration. Raltegravir is a
      novel HIV-1 integrase strand transfer inhibitor with potent in vitro activity
      against wild-type and multi-class resistant HIV-1 virus (in vitro IC(95) for HIV
      1 in 50% normal human serum = 33 nM). Inhibition of integrase prevents insertion
      of HIV DNA into the human DNA genome, thus blocking the ability of HIV to
      replicate. Raltegravir is administered orally every 12 h and does not require
      boosting with low-dose ritonavir (RTV) to achieve therapeutic concentrations.
      Raltegravir is not a potent inhibitor or inducer of cytochrome P450 3A4, and it
      is predominantly metabolized by glucuronidation, specifically by the enzyme UDP
      glucuronosyltransferase 1A1.

PMID- 18095923
TI  - Update: vildagliptin for the treatment of Type 2 diabetes.
AB  - Vildagliptin is a selective inhibitor of dipeptidyl peptidase-4, and prevents the
      rapid degradation of the incretin hormones glucagon-like peptide-1 and glucose
      dependent insulinotropic polypeptide. Vildagliptin has been evaluated in > 4800
      patients in nine Phase III studies in the range of 24 - 52 weeks in duration:
      four placebo- or active-controlled monotherapy trials that enrolled drug-naive
      patients; four add-on studies in which vildagliptin was added to a stable regimen
      of either metformin, a sulfonylurea, a thiazolidinedione or insulin; and a study
      in which an initial combination of vildagliptin plus pioglitazone in drug-naive
      patients was evaluated. Across studies, vildagliptin was effective in reducing
      HbA(1c), had a low risk of hypoglycemia and was weight-neutral and well
      tolerated.

PMID- 18095924
TI  - Mining nanodiamonds for drug delivery.

PMID- 18095925
TI  - Sustained transscleral drug delivery.
AB  - Transscleral delivery is an emerging, high-potential method for delivering drugs
      to the posterior eye. If successful, it could offer non-invasiveness comparable
      to drops and delivery efficiency comparable to intravitreal injection. However,
      there are numerous challenges to be overcome before transscleral delivery will be
      a significant treatment option. The resistance of the sclera is extremely well
      understood, but the other tissues, especially the retinal pigment epithelium,
      clearly demand more attention and the effect of drug chemistry remains poorly
      understood. In this review, the major research on transscleral delivery with an
      emphasis on current understanding of these points and open questions for the
      field is summarized.

PMID- 18095927
TI  - Liposomal nanomedicines.
AB  - Liposomal nanoparticles (LNs) encapsulating therapeutic agents, or liposomal
      nanomedicines, represent an advanced class of drug delivery systems, with several
      formulations presently on the market and many more in clinical trials. Over the
      past 20 years, a variety of techniques have been developed for encapsulating both
      conventional drugs (such as anticancer drugs and antibiotics) and the new genetic
      drugs (plasmid DNA containing therapeutic genes, antisense oligonucleotides and
      small interfering RNA) within LNs. If the LNs possess certain properties, they
      tend to accumulate at sites of disease, such as tumours, where the endothelial
      layer is 'leaky' and allows extravasation of particles with small diameters.
      These properties include a diameter centred on 100 nm, a high drug-to-lipid
      ratio, excellent retention of the encapsulated drug, and a long (> 6 h)
      circulation lifetime. These properties permit the LNs to protect their contents
      during circulation, prevent contact with healthy tissues, and accumulate at sites
      of disease. The authors discuss recent advances in this field involving
      conventional anticancer drugs, as well as applications involving gene delivery,
      stimulation of the immune system and silencing of unwanted gene expression.
      Liposomal nanomedicines have the potential to offer new treatments in such areas
      as cancer therapy, vaccine development and cholesterol management.

PMID- 18095926
TI  - Liposome-nucleic acid immunotherapeutics.
AB  - Cationic liposome-nucleic acid complexes, which were originally developed for use
      as non-viral gene delivery vectors, may now have an equally important application
      as immunotherapeutic drugs. Recent studies have highlighted the ability of
      cationic liposomes to potently activate the innate immune system when used to
      deliver certain Toll-like receptor (TLR) agonists. The immune-enhancing
      properties of cationic liposomes have been most clearly demonstrated when
      combined with nucleic acid agonists for endosomally located TLRs, including TLR3,
      TLR7/8 and TLR9. Immune potentiation by cationic liposomes likely results from
      the combined effects of endosomal targeting, protection of nucleic acids from
      extracellular degradation, and from signaling via newly identified cytoplasmic
      receptors for nucleic acids. The potent innate immune stimulatory properties of
      liposome-nucleic acid complexes make them particularly attractive as non-specific
      immunotherapeutics and as vaccine adjuvants. Liposome-nucleic acid complexes have
      demonstrated impressive anticancer activity in a number of different animal tumor
      models. Moreover, liposome-nucleic acid complexes have also been shown to be
      effective for immunotherapy of acute viral and bacterial infections, as well as
      chronic fungal infections. When used as vaccine adjuvants, liposome-nucleic acid
      complexes target antigens for efficient uptake by dendritic cells and are
      particularly effective in eliciting CD8(+) T-cell responses to protein antigens.
      Thus, liposome-nucleic acid complexes form a potent and versatile
      immunotherapeutic platform.

PMID- 18095928
TI  - Nanoparticle strategies for the oral delivery of insulin.
AB  - Since its discovery, insulin remains the major treatment for Type 1 diabetes and
      many Type 2 diabetic patients, with insulin being administered parenterally. The
      oral route of insulin delivery, being the most comfortable, would also be the
      most physiologically advantageous in taking advantage of the portal-hepatic route
      of absorption. However, insulin is less absorbed by the intestinal mucosa and is
      rapidly degraded enzymatically in the gastrointestinal tract. Polymeric
      biodegradable and biocompatible nanoparticles have been developed. These
      nanoparticles protect insulin against degradation and facilitate the uptake of
      insulin (associated or not associated to the nanoparticles) through a
      paracellular or a transcellular pathway. In this review, the physicochemical
      characteristics of polymer composition, in vitro release kinetics and the
      biological effects of insulin-loaded nanoparticles in experimental diabetes and
      healthy animals are discussed.

PMID- 18095929
TI  - Past and future evolution in colloidal drug delivery systems.
AB  - Colloidal drug delivery systems have been providing alternative formulation
      approaches for problematic drug candidates, and improved delivery for existing
      compounds for decades. Colloidal systems for drug delivery have all evolved down
      a similar pathway, almost irrespective of the delivery system, from conception,
      to the use of safer excipients, PEGylation for passive targeting and attachment
      of ligands for active targeting. The recent emergence of truly biologically
      interactive systems represents the latest step forward in colloidal delivery
      systems. In this article, the maturation pathway and recent advances for the
      major classes of colloidal delivery systems are reviewed, and the paper poses the
      question of whether the nanotechnology boom will create a revolution in colloidal
      delivery, or just the next natural stage in evolution.

PMID- 18095930
TI  - Trends in immunoconjugate and ligand-receptor based targeting development for
      cancer therapy.
AB  - Many agents used to treat cancer are toxic to normal tissues. Thus, treatments
      delivering drug specifically to tumour, while minimising exposure to normal
      tissue, may be advantageous over non-targeted treatments. The exquisite
      specificity of the immune system has been used successfully to help develop
      targeted anticancer agents. The most common (and successful) tissue-specific
      targeting strategies rely on antibody conjugates, but additional approaches,
      including targeting through cytokines, peptides and recombinant viruses, have
      also been used successfully. This review summarises the agents exploiting the
      immunological principles of target specificity to help maximise delivery to
      tumour while minimising collateral damage to normal tissues. Such targeted
      molecules are collectively referred to as immunoconjugates.

PMID- 18095931
TI  - Cell-penetrating peptides for drug delivery across membrane barriers.
AB  - During the last decade, cell-penetrating peptides have been investigated for
      their ability to overcome the plasma membrane barrier of mammalian cells for the
      intracellular or transcellular delivery of cargoes as diverse as low molecular
      weight drugs, imaging agents, oligonucleotides, peptides, proteins and colloidal
      carriers such as liposomes and polymeric nanoparticles. Their ability to cross
      biological membranes in a non-disruptive way without apparent toxicity is highly
      desired for increasing drug bioavailability. This review provides an overview of
      the application of cell-penetrating peptides as transmembrane drug delivery
      agents, according to the recent literature, and discusses critical issues and
      future challenges in relation to fully understanding the fundamental principles
      of the cell-penetrating peptide-mediated membrane translocation of cargoes and
      the exploitation of their therapeutic potential.

PMID- 18095932
TI  - Microemulsions as novel drug carriers: the formation, stability, applications and
      toxicity.
AB  - A microemulsion, made from water, oil, surfactants and cosurfactant is a
      thermodynamically stable system. The presence of the cosurfactant is often
      required in order to lower the interfacial tension of this interface, because a
      low interfacial tension is essential for the formation of microemulsions. The
      transparency of microemulsions arises from their small droplet diameter. The
      droplet diameter in stable microemulsions is usually within the range of 10 - 140
      nm. Microemulsions are graphically represented as stability areas in triangular
      phase diagrams where each triangular corner designates a certain component.
      Microemulsions are actually quaternary (pseudoternary) systems. In pharmaceutical
      fields, the interest in microemulsions is increasing and, thus, they are applied
      to various administration routes.

PMID- 18095933
TI  - Electromotive drug administration with mitomycin C for intravesical treatment of
      non-muscle invasive transitional cell carcinoma.
AB  - This article reviews the use and application of electromotive drug administration
      for the intravesical treatment of bladder cancer. Strong evidence supports the
      use of passive intravesical chemotherapy in the management of non-muscle invasive
      bladder cancer. More recently, two published randomised trials have shown
      therapeutic advantage with protocols that use electromotive drug administration
      to enhance urothelial penetration of intravesical mitomycin C. The results
      suggest that the passive intravesical administration of chemotherapeutic drugs
      may be suboptimal. Further studies are required to demonstrate the feasibility
      and advantage of electromotive intravesical mitomycin C in the wider uro
      oncological community.

PMID- 18095937
TI  - A Ca2+-dependent bacterial antifreeze protein domain has a novel beta-helical ice
      binding fold.
AB  - AFPs (antifreeze proteins) are produced by many organisms that inhabit ice-laden
      environments. They facilitate survival at sub-zero temperatures by binding to,
      and inhibiting, the growth of ice crystals in solution. The Antarctic bacterium
      Marinomonas primoryensis produces an exceptionally large(>1 MDa) hyperactive Ca2+
      dependent AFP. We have cloned,expressed and characterized a 322-amino-acid region
      of the protein where the antifreeze activity is localized that shows similarity
      to the RTX (repeats-in-toxin) family of proteins. The recombinant protein
      requires Ca2+ for structure and activity, and it is capable of depressing the
      freezing point of a solution in excess of 2 degrees C at a concentration of 0.5
      mg/ml, therefore classifying it as a hyperactive AFP. We have developed a
      homology-guided model of the antifreeze region based partly on the Ca2+-bound
      beta-roll from alkaline protease. The model has identified both a novel beta
      helical fold and an ice-binding site. The interior of the beta-helix contains a
      single row of bound Ca2+ ions down one side of the structure and a hydrophobic
      core down the opposite side. The ice binding surface consists of parallel
      repetitive arrays of threonine and aspartic acid/asparagine residues located down
      the Ca2+-bound side of the structure. The model was tested and validated by site
      directed mutagenesis. It explains the Ca2+-dependency of the region, as well its
      hyperactive antifreeze activity. This is the first bacterial AFP to be
      structurally characterized and is one of only five hyperactive AFPs identified to
      date.AFPS

PMID- 18095938
TI  - ArHsp21, a developmentally regulated small heat-shock protein synthesized in
      diapausing embryos of Artemia franciscana.
AB  - Embryos of the crustacean, Artemia franciscana, undergo alternative developmental
      pathways, producing either larvae or encysted embryos (cysts). The cysts enter
      diapause, characterized by exceptionally high resistance to environmental stress,
      a condition thought to involve the sHSP (small heat-shock protein), p26.
      Subtractive hybridization has revealed another sHSP, termed ArHsp21, in diapause
      destined Artemia embryos. ArHsp21 shares sequence similarity with p26 and sHSPs
      from other organisms, especially in the alpha-crystallin domain. ArHsp21 is the
      product of a single gene and its synthesis occurred exclusively in diapause
      destined embryos. Specifically, ArHsp21 mRNA appeared 2 days post-fertilization,
      followed 1 day later by the protein, and then increased until embryo release at
      day 5. No ArHsp21 protein was detected in embryos developing directly into
      larvae, although there was a small amount of mRNA at 3 days post-fertilization.
      The protein was degraded during post-diapause development and had disappeared
      completely from second instar larvae. ArHsp21 formed large oligomers in encysted
      embryos and transformed bacteria. When purified from bacteria, ArHsp21 functioned
      as a molecular chaperone in vitro, preventing heat-induced aggregation of citrate
      synthase and reduction-driven denaturation of insulin. Sequence characteristics,
      synthesis patterns and functional properties demonstrate clearly that ArHsp21 is
      an sHSP able to chaperone other proteins and contribute to stress tolerance
      during diapause. As such, ArHsp21 would augment p26 chaperone activity and it may
      also possess novel activities that benefit Artemia embryos exposed to stress.

PMID- 18095940
TI  - Apoptosis pathways and oncolytic adenoviral vectors: promising targets and tools
      to overcome therapy resistance of malignant melanoma.
AB  - In the last decades melanoma incidence has been increasing worldwide, while
      mortality remained on a high level. Until now, there is no suitable therapy for
      metastasized melanoma, which could lead to a significant increase in overall
      survival. Apoptosis deficiency is supposed to be a critical factor for therapy
      resistance, and previous work has characterized the basic mechanisms of apoptosis
      regulation in melanoma. Genes and strategies suitable for efficient induction of
      apoptosis in melanoma cells were identified, which are based on proapoptotic Bcl
      2 proteins (Bcl-x(S), Bcl-x(AK), Bik/Nbk and Bax) as well as on tumor necrosis
      factor (TNF)-related death ligands (CD95L/Fas ligand and TNF-related apoptosis
      inducing ligand, TRAIL). Proapoptotic genes may be employed in improved gene
      therapeutic strategies, based on conditional oncolytic adenoviral vectors.

PMID- 18095939
TI  - Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that
      has undergone rapid evolutionary change.
AB  - We have isolated cDNAs encoding PDE4A8 (phosphodiesterase 4 isoform A8), a new
      human cAMP-specific PDE4 isoform encoded by the PDE4A gene. PDE4A8 has a novel N
      terminal region of 85 amino acids that differs from those of the related 'long'
      PDE4A4, PDE4A10 and PDE4A11 isoforms. The human PDE4A8 N-terminal region has
      diverged substantially from the corresponding isoforms in the rat and other
      mammals, consistent with rapid evolutionary change in this region of the protein.
      When expressed in COS-7 cells, PDE4A8 localized predominantly in the cytosol, but
      approx. 20% of the enzyme was associated with membrane fractions. Cytosolic
      PDE4A8 was exquisitely sensitive to inhibition by the prototypical PDE4 inhibitor
      rolipram (IC(50) of 11+/-1 nM compared with 1600 nM for PDE4A4), but was less
      sensitive to inhibition by cilomilast (IC(50) of 101+/-7 nM compared with 61 nM
      for PDE4A4). PDE4A8 mRNA was found to be expressed predominantly in skeletal
      muscle and brain, a pattern that differs from the tissue expression of other
      human PDE4 isoforms and also from that of rat PDE4A8. Immunohistochemical
      analysis showed that PDE4A8 could be detected in discrete regions of human brain,
      including the cerebellum, spinal cord and cerebral cortex. The unique tissue
      distribution of PDE4A8, combined with the evolutionary divergence of its N
      terminus, suggest that this isoform may have a specific function in regulating
      cAMP levels in human skeletal muscle and brain.

PMID- 18095941
TI  - Human epidermal Langerhans cells express the tight junction protein claudin-1 and
      are present in human genetic claudin-1 deficiency (NISCH syndrome).
AB  - Claudin-1 (CLDN1) is a structural tight junction (TJ) protein and is expressed in
      differentiating keratinocytes and Langerhans cells in the epidermis. Our
      objective was to identify immunoreactive CLDN1 in human epidermal Langerhans
      cells and to examine the pattern of epidermal Langerhans cells in genetic human
      CLDN1 deficiency [neonatal ichthyosis, sclerosing cholangitis (NISCH) syndrome].
      Epidermal cells from healthy human skin labelled with CLDN1-specific antibodies
      were analysed by confocal laser immunofluorescence microscopy and flow cytometry.
      Skin biopsy sections of two patients with NISCH syndrome were stained with an
      antibody to CD1a expressed on epidermal Langerhans cells. Epidermal Langerhans
      cells and a subpopulation of keratinocytes from healthy skin were positive for
      CLDN1. The gross number and distribution of epidermal Langerhans cells of two
      patients with molecularly confirmed NISCH syndrome, however, was not grossly
      altered. Therefore, CLDN1 is unlikely to play a critical role in migration of
      Langerhans cells (or their precursors) to the epidermis or their positioning
      within the epidermis. Our findings do not exclude a role of this TJ molecule once
      Langerhans cells have left the epidermis for draining lymph nodes.

PMID- 18095942
TI  - CCR4 and CCR10 ligands play additive roles in mouse contact hypersensitivity.
AB  - Psoriasis, atopic dermatitis and allergic contact dermatitis are T-cell-mediated
      inflammatory skin diseases; chemokine receptors (CCR) 4 and 10 play an important
      role in the ligand-mediated recruitment of T cells into the skin in mice and
      humans, specifically with regards to tethering, firm adhesion and subsequent
      extravasation to the sight of injury. We utilized established murine models of
      dinitrofluorobenzene-, trimellitic acid anhydride- or oxazalone-induced contact
      hypersensitivity, to reflect the various Th-polarizations of different skin
      diseases, and investigated the functional effect of antibody blocking of single
      CCR ligands or combination therapy to block all CCR4 and CCR10 ligands. Our
      results indicate a greater reduction in inflammatory response--measured by oedema
      formation, myeloid cell and neutrophil infiltration and activity and CD3+ cell
      infiltration at the site of injury--with combination antibody therapy to CCR4 and
      CCR10 ligands versus controls, in nearly every tested condition. We conclude that
      blocking CCR4 and CCR10 simultaneously, or their ligands, should be beneficial in
      the treatment of T-cell-mediated skin diseases.

PMID- 18095943
TI  - IgG against extracellular subdomains of desmoglein 3 relates to clinical
      phenotype of pemphigus vulgaris.
AB  - Pemphigus vulgaris (PV) is associated with autoantibodies against desmoglein
      (Dsg) 3 inducing epidermal loss of adhesion. The major pathogenic epitopes of
      Dsg3 are presumably dependent of their conformation. The aim of this study was to
      characterize the IgG reactivity of sera from a cohort of clinically well
      characterized PV patients against presumably non-conformational subdomains of the
      Dsg3 ectodomain including recently described NH2-terminal immunodominant
      epitopes. By ELISA, IgG reactivity against distinct subdomains of Dsg3 was
      related to disease activity and the clinical phenotype of PV patients. Our
      findings suggest that (i) autoantibody from PV sera react with non-conformational
      epitopes of Dsg3; (ii) IgG reactivity against the NH2-terminus and the
      extracellular domains (EC) 2-4 of Dsg3 was associated with active PV, while IgG
      titres were not strictly correlated with disease activity and (iii) IgG
      reactivity against the EC1-4 was associated with mucosal dominant PV and was
      decreased in cutaneous dominant PV. The findings may help to define more refined
      serological disease markers of PV.

PMID- 18095944
TI  - Production of anti-epithelial antibodies and acantholysis by vaccination with an
      anti-idiotypic antibody, mimicking desmoglein 1.
AB  - Theoretically, the immunization of experimental animals with an anti-idiotype
      antibody may elicit antibodies that recognize epitopes like the original
      idiotype; this is archived via internal images. Using this strategy, we attempted
      to produce anti-epithelial antibodies in Balb/c mice immunized with a pemphigus
      anti-idiotypic determinant. First, when an anti-idiotype antibody was produced in
      rabbits by immunization with pemphigus immunoglobulin G (IgG), the anti-idiotypic
      activity was tested successfully. The anti-idiotype IgG was digested with pepsin
      and purified by gel filtration chromatography to obtain F(ab')(2) fragments,
      which were used to immunize Balb/c mice. A control group was immunized with
      normal IgG. The experimental animals immunized with anti-idiotype F(ab')(2)
      fragments developed anti-epithelial antibodies in the following two months. The
      elicited antibodies had anti-desmoglein 1 specificity. Additionally, the skin
      biopsies of these animals exhibited antibody deposition along intercellular
      spaces of epidermis, and 25% of them developed blisters. Sera and skin biopsies
      of control Balb/c mice group were negative. In conclusion, the immunization with
      pemphigus anti-idiotype antibody may elicit anti-epithelial antibodies via
      internal images. This experimental approach can be used to understand the
      pathogenic mechanisms of pemphigus.

PMID- 18095945
TI  - Molecular determination of laminin-5 degradation: a biomarker for mustard gas
      exposure diagnosis and its mechanism of action.
AB  - Laminin-5, a heterotrimer of laminin alpha3, beta3 and gamma2 subunits, is a
      component of epithelial cell basement membranes. Laminin-5 functions as a ligand
      of the alpha3beta1 and alpha6beta4 integrins to regulate cell adhesion, migration
      and morphogenesis. In the skin, laminin-5 facilitates the assembly of basement
      membranes; thus it is essential for a stable attachment of the epidermis to the
      dermis and recovery of damaged skin. Sulphur mustard (SM), also known as mustard
      gas, is a vesicant that has been employed as a chemical weapon in various
      conflicts during the twentieth century. Skin exposure to SM results in fluid
      filled blisters; proposed mechanisms are inflammation, protease stimulation,
      basal cell death and separation of the epidermis from the dermis apparently
      because of the degradation of attachment proteins like laminin-5. Therefore, we
      investigated the effects of SM exposure on the degradation of laminin-5 and its
      three subunits, alpha3, beta3 and gamma2 by exposing normal human epidermal
      keratinocytes (NHEK) to SM (0-300 microM, 1-24 h). We found that SM degraded
      laminin-5 and its two subunits beta3 and gamma2, but not alpha3. Preincubation of
      cells with a serine protease inhibitor (PMSF), or a metalloprotease inhibitor
      (1,10-phenanthroline) prior to SM exposure partially prevented SM-induced
      degradation of laminin-5 subunits, beta3 and gamma2. Specificity studies showed
      that the degradation of laminin-5 gamma2 was due to a bifunctional mustard
      compound such as SM, but not due to the other alkylating agents tested. Our
      results support that laminin-5 degradation is an important mechanism of SM injury
      as well as a useful biomarker of SM exposure. The knowledge of the mechanisms of
      laminin-5 degradation in SM-exposed NHEK has potential application in developing
      cutaneous therapeutics against SM.

PMID- 18095946
TI  - Topical tacrolimus in combination with simulated solar radiation does not enhance
      photocarcinogenesis in hairless mice.
AB  - Numerous studies have demonstrated the utility of topical tacrolimus ointment in
      atopic dermatitis. However, there is a concern that local immunosuppression by
      calcineurin inhibitors may enhance dermal photocarcinogenesis and carcinogenesis.
      Therefore, we investigated the influence of topical tacrolimus ointment on
      squamous cell carcinoma formation in hairless female C3.Cg/TifBomTac
      immunocompetent mice exposed to solar simulated radiation (SSR). In a first
      experiment, mice (n = 200) had tacrolimus applied on their dorsal skin three
      times weekly followed by SSR (2, 4 or 6 standard erythema doses, SED) 3-4 h
      later. Tacrolimus did not reduce the time to tumor development and in the group
      receiving 4 SED it even had a protective effect (156 days vs 170 days, P =
      0.008). In a second experiment, mice (n = 50) were irradiated with 6 SED three
      times weekly for 3 months and subsequently treated five times weekly with topical
      tacrolimus to mimic the use of tacrolimus on sun-damaged skin. The median time to
      the first skin tumor was 234 days in SSR + tacrolimus group compared with 227
      days in the only SSR-irradiated group (P = 0.160). In a third experiment, mice (n
      = 25) had tacrolimus applied on their dorsal skin every day for 1 month,
      thereafter the group was irradiated with 4 SED three times weekly. The median
      time to the first skin tumor was 142 days in tacrolimus + SSR group compared with
      156 days in the only SSR-irradiated group from experiment 1 (P = 0.363). We
      conclude that tacrolimus ointment does not accelerate photocarcinogenesis or
      induce any dermal carcinogenicity in hairless mice.

PMID- 18095947
TI  - Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR
      alpha/-gamma activator properties.
AB  - PPARs are transcription factors belonging to the superfamily of nuclear
      receptors. PPAR-alpha is involved in the regulation of fatty acid (FA) uptake and
      oxidation, inflammation and vascular function, while PPAR-gamma participates in
      FA uptake and storage, glucose homeostasis and inflammation. The PPARs are thus
      major regulators of lipid and glucose metabolism. Synthetic PPAR-alpha or PPAR
      gamma agonists have been widely used in the treatment of dyslipidaemia,
      hyperglycaemia and their complications. However, they are associated with an
      incidence of adverse events. Given the favourable metabolic effects of both PPAR
      alpha and PPAR-gamma activators, as well as their potential to modulate vascular
      disease, combined PPAR-alpha/-gamma activation has recently emerged as a
      promising concept, leading to the development of mixed PPAR-alpha/-gamma
      activators. However, some major side effects associated with the synthetic dual
      activators have been reported. It is unclear whether this is a specific effect of
      the particular synthetic compounds or a class effect. To date, a medication that
      may combine the beneficial metabolic effects of PPAR-alpha and PPAR-gamma
      activation with fewer undesirable side effects has not been successfully
      developed. Pomegranate plant parts are used traditionally for the treatment of
      various disorders. However, only pomegranate flower has been prescribed in Unani
      and Ayurvedic medicines for the treatment of diabetes. This review provides a new
      understanding of the dual PPAR-alpha/-gamma activator properties of pomegranate
      flower in the potential treatment of diabetes and its associated complications.

PMID- 18095948
TI  - Improvement of glycaemia control in subjects with type 2 diabetes by self
      monitoring of blood glucose: comparison of two management programs adjusting
      bedtime insulin dosage.
AB  - AIM: Self-monitoring of blood glucose (SMBG) is important for patients treated
      with insulin to detect asymptomatic hypoglycaemia and to guide patients towards
      reaching blood glucose goal. This study compared two management programs for
      adjusting bedtime insulin dose: program 1 (performed by study subjects) vs.
      program 2 (performed by study subjects and reminded by investigators). METHODS:
      This is a prospective, open-level, 28-week randomized trial in poorly controlled
      type 2 diabetic subjects. One hundred subjects treated with oral antidiabetic
      drugs plus bedtime insulin with glycated haemoglobin A(1C) (A1C) >8.0% were
      screened and received a structure education package in a 4-week run-in period.
      Seventy-eight subjects were randomized to two treatment programs (adjust insulin
      dose by themselves with or without investigators' reminder) and reviewed by the
      investigators at a 4-week interval clinical visit. RESULTS: The mean SMBG
      decreased significantly in both groups, with a greater decrease observed in
      program 2 vs. program 1 (from 198.7 +/- 43.1 to 122.6 +/- 21.9 mg/dl vs. from
      194.0 +/- 42.7 to 151.6 +/- 37.7 mg/dl, p < 0.001). Bedtime insulin dose
      increased in both groups with a greater increase in program 2 (from 14.4 +/- 8.7
      to 27.4 +/- 12.8 IU vs. from 14.3 +/- 8.3 to 18.4 +/- 6.2 IU, p < 0.001). There
      was a significant reduction in A1C from 9.54 +/- 1.67% to 7.76 +/- 1.27%, with a
      greater decrease (p < 0.001) in program 2 (2.17%) than in program 1 (1.40%).
      There were more subjects in the program 2 group achieving the treating targets:
      mean SMBG < or =120 mg/dl (46.9 vs. 17.9%) and A1C < or =7.0% (54.5 vs. 32.2%).
      There was no significant difference in the incidence of hypoglycaemia and body
      weight changes. CONCLUSIONS: Systematically titrating bedtime insulin dose added
      to oral therapy, especially combined with health care reminders, can safely
      improve glycaemic control in type 2 diabetes with poor glycaemic control. This
      regimen may facilitate safe and effective insulin therapy in routine medical
      practice and improve achievement of recommended standards of diabetes care.

PMID- 18095949
TI  - Tissue angiotensin-converting enzyme inhibitors for the prevention of
      cardiovascular disease in patients with diabetes mellitus without left
      ventricular systolic dysfunction or clinical evidence of heart failure: a pooled
      meta-analysis of randomized placebo-controlled clinical trials.
AB  - AIM: The aim of this study was to determine the role of tissue angiotensin
      converting enzyme (ACE) inhibitors in the prevention of cardiovascular disease in
      patients with diabetes mellitus without left ventricular systolic dysfunction or
      clinical evidence of heart failure in randomized placebo-controlled clinical
      trials using pooled meta-analysis techniques. METHODS: Randomized placebo
      controlled clinical trials of at least 12 months duration in patients with
      diabetes mellitus without left ventricular systolic dysfunction or heart failure
      who had experienced a prior cardiovascular event or were at high cardiovascular
      risk were selected. A total of 10 328 patients (43 517 patient-years) from four
      selected trials were used for meta-analysis. Relative risk estimations were made
      using data pooled from the selected trials and statistical significance was
      determined using the Chi-squared test (two-sided alpha error <0.05). The number
      of patients needed to treat was also calculated. RESULTS: Tissue ACE inhibitors
      significantly reduced the risk of cardiovascular mortality by 14.9% (p = 0.022),
      myocardial infarction by 20.8% (p = 0.002) and the need for invasive coronary
      revascularization by 14% (p = 0.015) when compared to placebo. The risk of all
      cause mortality also tended to be lower among patients randomized to tissue ACE
      inhibitors, whereas the risks of stroke and hospitalization for heart failure
      were not significantly affected. Treating about 65 patients with tissue ACE
      inhibitors for about 4.2 years would prevent one myocardial infarction, whereas
      treating about 85 patients would prevent one cardiovascular death. CONCLUSION:
      Pooled meta-analysis of randomized placebo-controlled trials suggests that tissue
      ACE inhibitors modestly reduce the risk of myocardial infarction and
      cardiovascular death and tend to reduce overall mortality in diabetic patients
      without left ventricular systolic dysfunction or heart failure.

PMID- 18095950
TI  - Metformin-associated lactic acidosis in patients with renal impairment solely due
      to drug accumulation?
AB  - AIM: We suspect that the life-threatening complication of metformin-associated
      lactic acidosis, solely due to drug accumulation following renal impairment,
      occurs more frequently than that previously reported and is not necessarily
      associated with other predisposing factors for lactic acidosis. METHODS: During a
      period of 13 months, at a tertiary referral centre, the incidence of lactic
      acidosis of any aetiology was 12.8% [67 of 524 total intensive care unit (ICU)
      admissions]. Metformin-associated lactic acidosis solely as the result of drug
      accumulation was diagnosed in 6% of all the patients suffering from lactic
      acidosis (4 of 67 patients). RESULTS: These patients presented with severe
      circulatory shock due to lactic acidosis. We could not identify any predisposing
      factor for lactic acidosis other than renal impairment. Intercurrent
      deterioration of diabetic nephropathy was suspected to be responsible for the
      accumulation of metformin followed by lactic acidosis, finally resulting in
      multiorgan failure. The diagnosis was supported by extensively elevated serum
      levels of metformin. Two patients died during ICU treatment. CONCLUSIONS: Our
      data indicate that the incidence of metformin-associated lactic acidosis solely
      due to metformin accumulation is possible and underestimated. Symptoms of
      metformin-associated lactic acidosis are unspecific and physicians should be
      aware that metformin, if prescribed in patients with renal impairment, can cause
      fatal lactic acidosis due to drug accumulation.

PMID- 18095951
TI  - Re: Insulin therapy in type 2 diabetes patients failing oral agents: cost
      effectiveness of biphasic insulin aspart 70/30 vs. insulin glargine in the US.

PMID- 18095952
TI  - Allergy, family history of autoimmune diseases, and the risk of multiple
      sclerosis.
AB  - OBJECTIVE: Previous reports suggested an association between allergy,
      autoimmunity, and risk of multiple sclerosis (MS), but results have been
      inconsistent. The present study assessed the association between history of
      allergy and autoimmune diseases, and the risk of MS. METHODS: We conducted a case
      control study nested in the Nurses' Health Study (NHS) and NHS II cohorts. A
      total of 298 women with MS were matched with 1248 healthy controls and 248 women
      with history of breast cancer. A mailed questionnaire gathered information about
      history of allergic conditions and autoimmune disorders. RESULTS: History of
      allergy was not associated with MS risk [odds ratio (OR) 1.0, 95% confidence
      interval (CI) 0.8-1.4]. As expected, cases were more likely to have a positive
      family history of MS than controls (OR 9.7, 95% CI 6.1-15.3). A modest
      association was found between family history of other autoimmune diseases and MS
      risk (OR 1.4, 95% CI 1.0-1.8). We obtained similar results when we used women
      with breast cancer as comparison group. CONCLUSION: Family history of other
      autoimmune diseases was associated with a higher MS risk, suggesting a common
      genetic background or shared environmental triggers. There was no clear
      association between personal history of allergy and risk of MS.

PMID- 18095953
TI  - Assessment of hallucinations in Parkinson's disease using a novel scale.
AB  - OBJECTIVE: To assess hallucinations in Parkinson's disease (PD), we developed a
      novel practical rating scale that evaluates five items including variety,
      frequency, and severity of hallucinations, caregiver burden levels, and
      psychiatric status at nighttime. METHODS: Forty-one PD patients and their
      caregivers were examined regarding the status of the hallucinations associated
      with PD. RESULTS: As a measure of internal consistency, the Tottori University
      Hallucination Rating Scale (TUHARS) has a Cronbach's alpha of 0.88. Mini-Mental
      State Examination (MMSE) and Hoehn-Yahr stage were associated with the TUHARS
      scores in a multivariate regression analysis. Visual hallucinations are the most
      common. However, half of the patients who reported visual hallucinations also had
      other hallucinations. The scale scores in the PD patients with dementia (PDD)
      group were significantly greater than in the PD patients without dementia (PDnD)
      group. CONCLUSIONS: TUHARS appears to be a suitable and easily administered
      instrument for assessment of hallucinations in PD. PD patients experienced
      various kinds of hallucinations. Hallucinations may have a close relationship
      with cognitive decline in PD patients.

PMID- 18095954
TI  - Spinocerebellar ataxia type 8 in Scotland: frequency, neurological,
      neuropsychological and neuropsychiatric findings.
AB  - OBJECTIVES: The objectives of this study were to: (i) establish whether the
      spinocerebellar ataxia type 8 (SCA 8) expansion is associated with ataxia in
      Scotland; (ii) test the hypothesis that SCA 8 is associated with
      neuropsychological impairment; and (iii) review neuroradiological findings in SCA
      8. METHODS: The methods included: (i) measurement of SCA 8 expansion frequencies
      in ataxic patients and healthy controls; (ii) comprehensive neuropsychological
      assessment of patients with SCA 8 and matched controls, neuropsychiatric
      interview; and (iii) comparison of patient and matched control magnetic resonance
      imaging (MRI) scans. RESULTS: (i) 10/694 (1.4%) unrelated individuals with ataxia
      had combined CTA/CTG repeat expansions >100 compared to 1/1190 (0.08%) healthy
      controls (P < 0.0005); (ii) neuropsychological assessment revealed a dysexecutive
      syndrome among SCA 8 patients, not readily explained by motor or mood
      disturbance; neuropsychiatric symptoms occurred commonly; (iii) cerebellar
      atrophy was the only salient MRI abnormality in the patient group. CONCLUSIONS:
      The SCA 8 expansion is associated with ataxia in Scotland. The disorder is
      associated with a dysexecutive syndrome.

PMID- 18095955
TI  - Clinical aspects of bowel symptoms in Parkinson's disease.
AB  - BACKGROUND: The clinical importance of bowel symptoms in Parkinson's disease (PD)
      remains to be described in detail. METHODS: A 33-item questionnaire including
      background parameters, the Cleveland Constipation Score (CCS), and items from the
      Neurogenic Bowel Dysfunction score was sent to 468 PD patients. Results were
      compared to a control group (CG) (n = 45). A CCS of at least 15 was used to
      define severe constipation. RESULTS: Four hundred and sixteen subjects (89%)
      responded. Median CSS was only 4 (range 0-21) in PD and 2 (range 0-13) in the CG
      (P < 0.05). Severe constipation was found in 7% with PD and 0% in the CG (P <
      0.05). Incomplete emptying at defecation, need for assisted defecation and use of
      oral laxatives was reported more frequently by PD patients than by the CG (all P
      < 0.05). The severity of PD was associated with assisted defecation (P < 0.001),
      unsuccessful attempts at defecation (P < 0.001), incomplete emptying at
      defecation (P < 0.05), and the CCS (P < 0.01). Time since diagnosis was
      associated with infrequent defecation (P < 0.0001) and the CCS (P < 0.05). The
      use of levodopa was associated with less unsuccessful attempts at defecation (P <
      0.05). CONCLUSION: Most patients with PD only have minor constipation-related
      symptoms. However, severe constipation is associated with time since diagnosis
      and severity of disease.

PMID- 18095957
TI  - Round and round we go: sedation -- what is it, who does it, and have we made
      things safer for children?

PMID- 18095958
TI  - Guidelines for monitoring and management of pediatric patients during and after
      sedation for diagnostic and therapeutic procedures: an update.

PMID- 18095959
TI  - SIGN Guideline 58: safe sedation of children undergoing diagnostic and
      therapeutic procedures.

PMID- 18095960
TI  - Conscious sedation in pediatric dentistry. A short review of the current UK
      guidelines and the technique of inhalational sedation with nitrous oxide.

PMID- 18095961
TI  - Deep sedation and minimal anesthesia.

PMID- 18095962
TI  - Ketamine for procedural sedation and analgesia in pediatric emergency medicine: a
      UK perspective.

PMID- 18095963
TI  - Training and credentialing in procedural sedation and analgesia in children:
      lessons from the United States model.

PMID- 18095964
TI  - Investigating the pharmacodynamics of ketamine in children.
AB  - BACKGROUND: The aim of this study was to describe ketamine pharmacodynamics (PD)
      in children. Adult ketamine concentrations during recovery are reported as 0.74
      mg.l(-1) (sd 0.24 mg.l(-1)) with an EC(50) for anesthesia of 2 mg.l(-1) (sd 0.5
      mg.l(-1)), but pediatric data are few. METHODS: Children presenting for painful
      procedures in an Emergency Department were given ketamine 1-1.5 mg.kg(-1) i.v.
      Blood was assayed for ketamine on three to six occasions (median 3) over the
      subsequent 14-152 min (median 28.5). Procedures were videotaped. Level of
      sedation (0-5; unresponsive - spontaneously awake without stimulus) and a test of
      memory were recorded. PD was investigated using a variable slope E(max) model
      (sedation) or logistic regression (arousal time, memory) with nonlinear mixed
      effects models. RESULTS: In total 60 children were enrolled. Pharmacokinetic data
      were collected in 54 of these children and there were 43 children available for
      PD study. The mean age was 8.15 years (sd 3.5 years) and weight was 34.9 kg (sd
      15.8 kg). The half-time describing equilibration between the effect compartment
      and central compartment was 11 s (95% CI 0.07-20 s). The EC(50) for arousal was
      0.52 (90% CI 0.22-1.17) mg.l(-1). The E(max) model with a baseline (E(0)) of five
      (spontaneously awake without stimulus) yielded a fractional E(max) 0.939
      [coefficient of variability (CV) 24%], an EC(50) 0.56 (CV 136%) mg.l(-1) and a
      Hill coefficient 3.71. The EC(50) for recall memory was 0.44 (90% CI 0.09-1.70)
      mg.l(-1). The EC(50) for remembering was 0.38 (90% CI 0.12-1.75) mg.l(-1).
      CONCLUSIONS: Concentrations associated with arousal in children are analogous to
      adults. The ability to recall and remember occurs at similar concentrations to
      those associated with arousal. A concentration of 1 mg.l(-1) was associated with
      a sedation level of three or less (arouses to consciousness with moderate tactile
      or loud verbal stimulus) in 95% of children while 1.5 mg.l(-1) was associated
      with a sedation level of two or less (rouses slowly to consciousness with
      sustained painful stimulus) in 95% of children. These concentrations can be
      attained for 3-4 min after 1 mg.kg(-1) and 1.5 mg.kg(-1) ketamine IV bolus,
      respectively. The mean arousal time can be anticipated at approximately 10 min (1
      mg.kg(-1)) and 15 min (1.5 mg.kg(-1)).

PMID- 18095965
TI  - Propofol-ketamine vs propofol-fentanyl combinations for deep sedation and
      analgesia in pediatric patients undergoing burn dressing changes.
AB  - BACKGROUND: The aim of this study was to compare propofol-ketamine (PK) and
      propofol-fentanyl (PF) combinations for deep sedation and analgesia in pediatric
      burn wound dressing changes. METHODS: Thirty-two ASA physical status II and III
      inpatients with a second degree total burn surface area ranging from 5% to 25%
      were studied in a randomized, double blind fashion. Heart rate, systolic arterial
      pressure, peripheral oxygen saturation, respiratory rate and Ramsey sedation
      scores of all patients were recorded perioperatively. Patients were randomly
      assigned to receive either PK or PF: PK group (n = 17) received 1 mg.kg(-1)
      ketamine + 1.2 mg.kg(-1) propofol, and PF group (n = 15) received 1 microg.kg(-1)
      fentanyl + 1.2 mg.kg(-1) propofol for induction. Additional propofol (0.5-1
      mg.kg(-1)) was administered when the patients showed discomfort in both groups.
      If the patient showed discomfort and/or increase in heart rate or systolic
      arterial pressure, despite additional propofol dose, additional bolus of 0.5-1
      mg.kg(-1) ketamine or 0.5-1 microg.kg(-1) fentanyl was administered. RESULTS:
      There were no significant differences in heart rate, systolic arterial pressure,
      peripheral oxygen saturation, respiratory rate and sedation scores during the
      procedure between the groups. Restlessness during the procedure was seen in seven
      (47%) patients in Group PF and one (5.9%) patient in Group PK (P = 0.013).
      CONCLUSIONS: Both propofol-ketamine and propofol-fentanyl combinations provided
      effective sedation and analgesia during dressing changes in pediatric burn
      patients. But propofol-ketamine combination was superior to propofol-fentanyl
      combination because of more restlessness in patients given propofol-fentanyl.

PMID- 18095966
TI  - Sedation with ketamine and low-dose midazolam for short-term procedures requiring
      pharyngeal manipulation in young children.
AB  - BACKGROUND: Pediatric intestinal biopsy procedures including considerable
      transpharyngeal manipulation of a wire-guided metal capsule require adequate
      sedation or anesthesia. This retrospective cohort study was designed to evaluate
      intravenous sedation with ketamine and low-dose midazolam in young children
      undergoing these procedures before and also after discharge from the hospital.
      METHODS: A total of 244 biopsy procedures in 217 children under the age of 16
      years were evaluated. All anesthesia records were reviewed according to a defined
      study protocol and in 145 cases the parents were also interviewed by telephone to
      obtain further information on possible adverse effects before and after
      discharge. RESULTS: Ketamine and low-dose midazolam were carefully titrated by an
      experienced anesthesia team at an approximate dose ratio of 40 : 1 (total doses
      2.3 and 0.05 mg.kg(-1)) in continuously monitored spontaneously breathing
      children. Possibly associated problems before discharge were salivation (5.7%),
      vomiting (4.9%), oxygen desaturation (3.3%), laryngospasm (2.5%) and rash (1.2%)
      according to the patient records and blurred vision (27%), nausea and vomiting
      (19%), vertigo (13%) and hallucinations or nightmares (3.5%) according to
      telephone interviews. Few, mild and transient problems remained after discharge
      from the hospital. CONCLUSIONS: Careful titration of ketamine and low-dose
      midazolam provides adequate sedation for nonsurgical pediatric short-term
      procedures also requiring considerable pharyngeal manipulation, particularly
      considering the low number of serious airway problems such as laryngospasm. The
      high incidence of late postoperative problems suggests that prospective studies
      should be designed for long-term follow-up of young children subjected to
      sedation or anesthesia.

PMID- 18095967
TI  - Effect of propofol on emergence behavior in children after sevoflurane general
      anesthesia.
AB  - BACKGROUND: Emergence agitation (EA) is a postoperative behavior that may occur
      in children undergoing general anesthesia with inhaled agents. OBJECTIVES: The
      aim of the present study was to assess the effect of propofol administered at the
      end of sevoflurane anesthesia on the incidence and severity of EA in children
      undergoing magnetic resonance imaging (MRI). METHODS: Eighty-four children, 2-7
      years old, undergoing MRI were enrolled in this randomized double-blind study. No
      sedative premedication was administered prior to anesthesia induction. Anesthesia
      was induced and maintained with sevoflurane in N(2)O/O(2). Group P received
      propofol 1 mg.kg(-1) and group S received saline. Pediatric Anesthesia Emergence
      Delirium scale (PAEDs) was used to evaluate recovery characteristics upon
      awakening and during the first 30 min after emergence from anesthesia. Children
      with PAEDs >16 were considered agitated. EA was analyzed using the Mann-Whitney U
      test. Demographic data and other side effects were analyzed using the Student's t
      test. RESULTS: Eighty-three children completed the study. There were 42 children
      in group P. EA was diagnosed in two children in the propofol group (4.8%) and in
      11 children in the placebo group (26.8%, P < 0.05). Time to achieving
      postanesthesia care unit discharge criteria was not different between the two
      groups. CONCLUSIONS: The addition of propofol 1 mg.kg(-1) can significantly
      decrease the incidence of EA after sevoflurane general anesthesia in children
      undergoing nonpainful procedures.

PMID- 18095968
TI  - The electroencephalograph during anesthesia and emergence in infants and
      children.
AB  - BACKGROUND: The characteristics of the electroencephalogram (EEG) during
      anesthesia in children are poorly described. An understanding of the EEG during
      anesthesia may help explain and predict the performance of EEG-derived depth of
      anesthesia monitors in children. This study aims to describe the association
      between age and some basic characteristics of the EEG during nonstandardized
      anesthesia in children and infants. METHODS: Sixty-four children aged 9 days to
      12 years were enrolled in this observational physiological study. Anesthesia was
      given at the discretion of the anesthetist. EEG was recorded from after induction
      to emergence using a BRM2 brain monitor ''BrainZ Instruments, Auckland, New
      Zealand'' in parietal and frontal montages. For comparison, 90% spectral edge
      frequency (SEF-90) and power were determined at three points (equilibrium during
      anesthesia, when the volatile agent was discontinued and at emergence), and
      children were divided into three age groups (0-6 months, 6-24 months and 2-12
      years). RESULTS: Fifty-seven children had artifact-free EEG data. From
      equilibrium to emergence the mean forehead power decreased substantially in
      children aged 2-12 years (3171-153 microV(2), P < 0.001) and 6-24 months (756-140
      microV(2), P < 0.001) but no difference was found in infants aged 0-6 months (93
      63 microV(2), P = 0.4). From equilibrium to emergence mean forehead spectral edge
      frequency increased in children aged 2-12 years (10.8-13.7 Hz, P = 0.01) but no
      change was found in children aged 6-24 months (12.7-12.7 Hz, P = 0.9) or 0-6
      months (9.45-7.26 Hz, P = 0.08). Throughout emergence, infants demonstrated a
      discontinuous EEG pattern with intermittent bursts separated with low amplitude.
      CONCLUSIONS: During anesthesia, the EEG in infants is fundamentally different
      from the EEG in older children. This study supports the need for specific infant
      derived algorithms if EEG-derived anesthesia depth monitors are to be used in
      infants.

PMID- 18095969
TI  - Intranasal clonidine as a premedicant: three cases with unique indications.
AB  - Clonidine is experiencing increasing use in the pediatric population as a
      sedative and analgesic because of its central alpha2-adrenergic agonism. We
      report three cases of preoperative use of intranasal clonidine in pediatric
      patients, all for different indications. One patient was treated for preoperative
      agitation and hallucinations associated with oral midazolam. One patient was
      given clonidine as a premedicant. The third patient was treated for preoperative
      agitation and hypertension. All three patients had subjective resolution of
      indicated symptoms and none experienced adverse outcomes.

PMID- 18095970
TI  - Use of the ProSeal laryngeal mask airway in an infant with a repaired H-type
      tracheoesophageal fistula and tracheomalacia.
AB  - The ProSeal laryngeal mask airway (PLMA) is a relatively new airway device with
      design features that improve the quality of positive pressure ventilation (PPV)
      and may decrease the risk of gastric aspiration. We describe the use of this
      device for the anesthesia management of an infant with an esophagocutaneous
      fistula following repair of an H-type tracheoesophageal fistula and
      tracheomalacia, in which avoidance of tracheal intubation was desired. This case
      report demonstrates that the PLMA may be a useful and practical alternative to
      tracheal intubation in an infant with a tenuous airway.

PMID- 18095971
TI  - Awake tracheal intubation through the laryngeal mask in neonates with upper
      airway obstruction.
AB  - Neonates with Pierre Robin or Treacher-Collins syndrome are at risk of upper
      airway obstruction and may require surgical fixation of the tongue to the
      mandible. Such neonates are at high risk of hypoxia during induction of
      anesthesia and thus awake fiberoptic intubation would be required. We experienced
      neonates in whom awake fiberoptic intubation could not be carried out, because of
      severe hypoxia. Awake insertion of the laryngeal mask solved this problem. A 1
      month-old neonate with Pierre Robin syndrome and another with Treacher-Collins
      syndrome were scheduled for surgical fixation of the tongue to the mandible, for
      constant upper airway obstruction. In both patients, awake fiberoptic intubation
      was attempted but abandoned, because SpO(2) rapidly decreased during the
      attempts. Awake insertion of the laryngeal mask relieved upper airway obstruction
      and facilitated oxygenation. Fiberoptic intubation through the laryngeal mask was
      easily achieved. Anesthesia was then induced. No hypoxia occurred after insertion
      of the laryngeal mask. In a further two neonates with Treacher-Collins syndrome
      and in one neonate with Pierre Robin syndrome, awake fiberoptic intubation
      through the laryngeal mask was also successful. We believe that in neonates with
      predicted difficult intubation, who are at risk of upper airway obstruction and
      awake fiberoptic intubation could aggregate hypoxia, awake insertion of the
      laryngeal mask can be useful in facilitating oxygenation (by relieving upper
      airway obstruction) and in facilitating fiberoptic intubation.

PMID- 18095972
TI  - Isoflurane vs sevoflurane in emergence delirium: a misleading conclusion.

PMID- 18095973
TI  - Anesthesia in a child with Saethre-Chotzen syndrome.

PMID- 18095974
TI  - Regarding sevoflurane and emergence agitation...again!

PMID- 18095976
TI  - Re: ProSeal as an alternative to endotracheal intubation in pediatric
      laparoscopy.

PMID- 18095978
TI  - Postoperative cardiovascular instability caused by malfunctioning ventilatory
      dual knob.

PMID- 18095979
TI  - Transient Horner's syndrome in an infant after continuous upper thoracic
      paravertebral analgesia.

PMID- 18095980
TI  - Acute discontinuation syndrome from dexmedetomidine after protracted use in a
      pediatric patient.

PMID- 18095981
TI  - Sevoflurane vs ketamine-midazolam for the anesthetic management of children
      undergoing extracorporeal shock wave lithotripsy.

PMID- 18095982
TI  - Massive melena due to arginine-vasopressin for septic shock in two pediatric
      patients.

PMID- 18095983
TI  - ProSeal LMA for surfactant administration.

PMID- 18095984
TI  - Role of the T-piece.

PMID- 18095985
TI  - Ultrasonographic guidance for catheterization of the internal jugular vein via
      the posterior approach.

PMID- 18095987
TI  - Molecular genetic analysis of the BRCA2 tumor suppressor gene region in cutaneous
      squamous cell carcinomas.
AB  - BACKGROUND: Germ line mutations of the BRCA2 tumor suppressor gene with
      subsequent loss of the remaining wild-type BRCA2 allele have been identified in
      up to 35% of familial breast cancer cases. A high frequency of allelic loss at
      the BRCA2 gene locus has also been reported in a variety of sporadic epithelial
      tumors including oesophageal squamous cell carcinomas (SCC), and sporadic head
      and neck SCC. AIM: The present study aimed to examine the integrity of the BRCA2
      gene in cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance/loss of
      heterozygosity (AI/LOH) was examined in 22 histologically confirmed cutaneous SCC
      at two microsatellite markers, D13S260 (centromeric to the BRCA2 gene) and
      D13S267 (telomeric to the BRCA2 gene). Immunohistochemical analysis of BRCA2
      protein expression was also examined in the cutaneous SCC. RESULTS: AI/LOH at the
      D13S260 locus was found in eight of the 19 informative SCC, and AI/LOH at the
      D13S267 locus was found in 12 of the 18 informative SCC. Seven SCC showed allelic
      loss at both markers, and six SCC showed retention of heterozygosity at both
      markers. Expression of BRCA2 protein was only detected in six of the normal
      epidermises and three of the 21 SCC examined. CONCLUSION: AI/LOH of the BRCA2
      gene region was found to be common in the cutaneous SCC.

PMID- 18095988
TI  - Expression of HuR in Merkel cell carcinoma and in normal skin.
AB  - BACKGROUND: HuR is a ubiquitously expressed member of the Elav/Hu family of mRNA
      binding proteins, and its cytoplasmic expression has been recognised to
      participate in carcinogenesis. The aims of this study were to explore the
      expression pattern of HuR in primary Merkel cell carcinoma (MCC), lymph node
      metastases and non-neoplastic skin. METHODS: Twenty-two primary MCC samples and
      five lymph node metastases were evaluated for HuR expression by
      immunohistochemistry. The data were compared with clinical parameters. RESULTS:
      Nuclear and cytoplasmic HuR-staining patterns were observed. Nuclear
      immunoreactivity was observed in 91% of the primary tumors and in 80% of the
      lymph node metastases. Cytoplasm was positive in 27% of the primary tumors and in
      60% of the lymph node metastases. No cytoplasmic HuR immunoreactivity was
      detected in non-neoplastic skin. However, moderate to strong nuclear staining was
      found in normal epidermis and in the epithelium of hair follicles and sebaceous
      glands. Expression of HuR in MCC did not associate with clinicopathological
      parameters. CONCLUSIONS: Primary MCCs and their lymph node metastases as well as
      non-neoplastic skin show nuclear expression of HuR protein. In contrast to non
      neoplastic skin, a subset of MCC tumors show cytoplasmic HuR staining, which may
      contribute to carcinogenesis in MCC.

PMID- 18095989
TI  - Immunohistochemical and ultrastructural features of Langerhans cells in condyloma
      acuminatum.
AB  - BACKGROUND: There are few studies on the abnormal morphology of Langerhans cells
      (LCs) in condyloma acuminatum (CA) lesions and the essence of the abnormal
      morphology of LCs in CA lesions is still not well elucidated. The aim of this
      study was to further investigate the morphological features of LCs in CA lesions.
      METHODS: CD1a(+) LCs in 13 CA lesions and in 13 normal controls were labeled
      using immunohistochemistry and examined by light microscopy. Ultrastructural
      investigation on LCs in six CA lesions and in six normal controls was performed
      by electron microscopy. RESULTS: Compared with those in normal controls, most
      CD1a(+) LCs in CA lesions exhibited dysplastic dendrities and abnormal
      distribution. The number of CD1a(+) LCs in CA lesions (26.31 +/- 18.84) was
      statistically lower (p < 0.001) than that in normal controls (72.00 +/- 27.40).
      Electron microscopy showed that the number of Birbeck granules within lesional
      LCs (4.00 +/- 2.94) was significantly decreased (p < 0.001) than that within
      normal LCs (10.80 +/- 4.78). The ultrastructures of most lesional LCs displayed
      degenerative changes. CONCLUSIONS: The morphology of most LCs in CA lesions shows
      degenerative changes, which suggest that these LCs have been functionally
      impaired.

PMID- 18095991
TI  - Evaluation of the use of Congo red staining in the differential diagnosis of
      Candida vs. various other yeast-form fungal organisms.
AB  - The Congo red staining properties of Candida organisms in clinical tissue
      specimens have not, to the best of our knowledge, previously been reported. The
      objective of this study was to determine if the Congo red staining
      characteristics of Candida vs. Histoplasma, Pityrosporum and Blastomyces could
      provide useful diagnostic information. Archival tissue specimens that contained
      Histoplasma, Pityrosporum, Candida and Blastomyces were stained with Congo red.
      The results of the Congo red staining were compared with the diagnoses which were
      originally rendered on the tissue. Nine out of nine cases (100%) of Blastomyces
      were Gomori methenamine silver (GMS) positive and Congo red positive, seven out
      of seven cases (100%) of Histoplasma were GMS positive and Congo red negative,
      and eight out of eight cases (100%) that had Pityrosporum were GMS positive and
      Congo red positive; these results corroborate with previously described staining
      patterns for each respective organism. Nine out of nine cases (100%) that had
      Candida were GMS positive and Congo red negative. Differential Congo red staining
      of Candida organisms can provide a rapid and accurate method of diagnosis in
      tissue specimens vs. Blastomyces and Pityrosporum, but not vs. Histoplasma.

PMID- 18095990
TI  - Proliferation of HSP47-positive skin fibroblasts in dermatofibroma.
AB  - BACKGROUND: The cell origin of dermatofibroma (DF) has not been clarified
      satisfactorily. This study was undertaken to assess the distribution of
      fibroblasts and the relationship between fibroblasts and other constituent cells
      in DF by 47-kDa heat-shock protein (HSP47), a cell marker for skin fibroblast.
      METHODS: Immunohistochemistry was performed to evaluate the expression of HSP47
      and other cell markers in histological variants of DF. RESULTS: Almost all
      spindle-shaped cells showed strong immunoreactivity for HSP47 in DF. In the
      fibrocollagenous type, a common type of DF, HSP47-positive fibroblasts were the
      major constituent cells. In the cellular and atypical types, many constituent
      cells were positive for HSP47. Huge cells with bizarre nuclei, which are
      distinctive of the atypical type, showed immunoreactivity for HSP47, not for CD68
      or factor XIIIa (FXIIIa). In the histiocytic and angiomatous types, CD68-positive
      histiocytes were the major constituent cells, but many scattered spindle cells
      were positive for HSP47. FXIIIa-positive dermal dendritic cells were increased,
      irrespective of DF variants, whereas the cell number varied from case to case.
      CONCLUSIONS: Skin fibroblast is one of the major constituent cells in DF, and DF
      may be composed chiefly of two types of cell lineages, fibroblasts and bone
      marrow-derived monocyte/macrophages (dermal dendritic cells and/or histiocytes).

PMID- 18095992
TI  - Cutaneous lesions of dermatomyositis with supervening fibrosis.
AB  - BACKGROUND: Dermatomyositis (DM) is a distinctive systemic connective tissue
      disease whereby the skin defines a cardinal site of involvement. There exists a
      body of literature, which suggests that a significant component of its clinical
      manifestations may be related to endothelial cell injury. We have postulated in
      the past that anti-endothelial cell antibodies may be the defining trigger
      leading to endothelial cell dysfunction. The primary organs affected by DM are
      the skin and muscle. A significant albeit rare complication is pulmonary
      fibrosis, which our recent study postulated to be attributable to an autoimmune
      endothelialitis. DESIGN: We describe six patients, four women and two men who
      ranged in age from 3 to 60 years, and had classic clinical presentations and
      cutaneous lesions of DM without any supervening clinical changes indicative of
      cutaneous sclerosis. RESULTS: Skin biopsies showed cell-poor interface dermatitis
      with variable dermal mucin and C5b-9 within the cutaneous vasculature. However,
      at variance with classic DM was the presence of a sclerodermoid tissue reaction,
      which was of variable depth. All of these patients had severe muscle involvement.
      One pediatric patient had concomitant significant cutaneous, central nervous
      system and oral mucosal ischemic infarcts. Significant pulmonary disease ensued
      in the four adult patients, manifesting as pulmonary fibrosis in two, diffuse
      alveolar damage in one and diaphragmatic failure in one. In three patients,
      direct immunofluorescent studies were corroborative of immune-based microvascular
      injury while Western blot and/or indirect immunofluorescent studies showed anti
      endothelial cell antibody activity within the serum of three patients.
      CONCLUSIONS: The identification of sclerosis in biopsies of skin lesions typical
      clinically for DM may be a harbinger for more severe autoimmune-based endothelial
      cell injury phenomenon. One could speculate that its basis may be attributable to
      elevated serum levels of the natural fibrogenic factor, transforming growth
      factor beta, which in turn is released from damaged endothelium.

PMID- 18095993
TI  - Immunolabeling pattern of cytokeratin 19 expression may distinguish sebaceous
      tumors from basal cell carcinomas.
AB  - BACKGROUND: Distinction between sebaceous tumors and basal cell carcinomas can
      often pose diagnostic problems. Recent work with the antibody to cytokeratin 19
      (CK 19) has shown that this marker has high specificity for undifferentiated
      basaloid cells. Our aim was to evaluate the use of CK 19 staining patterns in
      differentiating between sebaceous tumors and basal cell carcinomas. The sebaceous
      tumors that were examined in this study included sebaceous adenomas, sebaceous
      epitheliomas (sebaceomas) and sebaceous carcinomas. METHODS: Thirty-seven cases
      including 5 sebaceous adenomas, 16 sebaceous epitheliomas, 6 sebaceous carcinomas
      and 14 basal cell carcinomas (7 being of the morpheaform type and 7 nodular basal
      cell carcinomas) were tested with a monoclonal mouse antibody to human CK 19.
      RESULTS: CK 19 was focally positive in 1/5 (20%) sebaceous adenomas, 8/16 (50%)
      of sebaceous epitheliomas and 1/6 (17%) of sebaceous carcinomas. Strongly
      positive expression of CK 19 was not seen in any of the sebaceous adenoma,
      sebaceous epithelioma or sebaceous carcinoma specimens. CK 19 was found to be
      strongly positive in 9/14 (64%) and focally positive in 2/14 (14%) of basal cell
      carcinomas. CONCLUSION: CK 19 expression can be helpful in differentiating
      sebaceous tumors (including sebaceous adenomas, sebaceous epitheliomas and
      sebaceous carcinomas) from basal cell carcinomas and may be a useful adjunct when
      these entities are included in the differential diagnosis.

PMID- 18095994
TI  - The morphologic spectrum of primary cutaneous anaplastic large T-cell lymphoma: a
      histopathologic study on 66 biopsy specimens from 47 patients with report of rare
      variants.
AB  - BACKGROUND: Primary cutaneous anaplastic large T-cell lymphoma (PCALCL) is a well
      defined entity with prognostic differences from the nodal counterpart [nodal
      anaplastic large cell lymphoma (NALCL)]. Several histological variants of NALCL
      have been characterized (common, lymphohistiocytic and small cell). However,
      studies on morphological variants of PCALCLs are lacking. METHODS: We analyzed
      retrospectively the clinicopathologic features of 66 biopsies from 47 patients (M
      : F = 27 : 20; median age: 53 years; mean age: 51.8 years; range: 14-82) with
      PCALCL, in order to better characterize the spectrum of this unusual neoplasm.
      RESULTS: The 'common variant' was the most frequent (40.4%). In contrast to
      NALCL, in PCALCL, marked reactive infiltrates are more commonly present. In fact,
      26 cases were classified as 'inflammatory type' (15 cases) and
      'lymphohistiocytic' (11 cases). Concerning the predominant cell morphology, large
      anaplastic cells (33%) were almost as frequent as large pleomorphic (36%) and
      small to medium-sized cells (26%). We reported for the first time in the skin 2
      rare cases with the predominance of large cells with a 'signet-ring'-like
      appearance. Epidermotropism and presence of eosinophils were found in a
      proportion of cases in all PCALCL variants. CONCLUSIONS: PCALCL is characterized
      by variable histopathological presentations and a broad cytomorphologic spectrum.

PMID- 18095996
TI  - Elastic tissue damage in cephalic acquired cutis laxa.
AB  - Cutis laxa is a rare condition characterized by diminished elastic tissue. We
      report the histological changes from a 22-year-old male patient, who presented
      since 4 years hanging and inelastic facial skin, giving him an older appearance.
      The palpebral, preauricular and submandibular skin obtained after a facelift were
      examined. Conventional light microscopy with hematoxylin-eosin staining showed
      perivascular lymphocytic infiltrates and crossed-over collagen fibers. With
      Weigert staining, a lessening of elastic fibers with fragmentation, shortening
      and clumping was seen. The oxytalanic fibers in the papillary dermis were also
      affected, ranging from absence or reduction to flattening with clumping of the
      fibers, giving an irregular contour to the basal membrane zone. These findings
      were more intense in the palpebral skin. Transmission electronic microscopy
      showed reduction of the elastic fibers, a granular degeneration of the elastic
      tissue was found and collagen fibers were normal. Similar to light microscopy, at
      the ultrastructural level, the basal membrane has an irregular contour.

PMID- 18095995
TI  - Metastatic cutaneous carcinoid tumor mimicking an adnexal poroid neoplasm.
AB  - OBJECTIVE: Metastatic cutaneous neoplasms may be difficult to differentiate from
      primary cutaneous neoplasms. Herein, we report an unusual case of metastatic
      cutaneous carcinoid tumor mimicking an adnexal poroid neoplasm. METHODS: A 53
      year-old male man presented with a neoplasm on the vertex of the scalp,
      clinically resembling a pigmented basal cell carcinoma. RESULTS: A shave biopsy
      was suggestive of an apocrine poroma, however, a metastatic carcinoma could not
      be excluded. After acquiring additional clinical information and the complete
      excision of the neoplasm, further immunohistochemical stains supported the
      diagnosis a metastatic carcinoid tumor. CONCLUSION: To our knowledge, this is the
      first case of metastatic carcinoid tumor reported that has mimicked a poroid
      neoplasm.

PMID- 18095997
TI  - Eruptive squamous cell carcinomas, keratoacanthoma type, arising in a multicolor
      tattoo.
AB  - Permanent tattoos are formed through the injection of ink solids through the
      epidermis into the dermis and can cause multiple adverse reactions. We report a
      38-year-old man who presented to our Dermatologic Surgery Unit with a diagnosis
      of a superficially invasive squamous cell carcinoma (SCC), keratoacanthoma (KA)
      type, of the left forearm in a 1-month-old tattoo. Since his initial biopsy, he
      developed four more similar lesions on his left forearm within his tattoo. On
      physical examination, the patient had a large, multicolor tattoo on his left
      forearm, a well-healed surgical biopsy site and four erythematous hyperkeratotic
      papules within differently pigmented areas of the patient's tattoo.
      Histopathological examination showed KA and tattoo pigment. Based on the eruptive
      nature of these lesions, their clinical presentation and the histopathological
      changes, we report this as the first case of eruptive KA arising in a multicolor
      tattoo.

PMID- 18095998
TI  - Dabska tumor arising in lymphangioma circumscriptum.
AB  - We describe a case of Dabska tumor (DT) occurring within a large congenital
      lymphangioma circumscriptum on the thigh of a 14-year-old female. Diagnostic
      biopsy showed numerous intravascular papillary projections lined by atypical
      endothelial cells within the anastomosing vascular channels of a lymphangioma
      circumscriptum. DT is regarded as a vascular tumor of intermediate malignant
      potential, most probably of lymphatic origin. Although it has been described in
      pre-existing lymphangiomas, to the best of our knowledge this is the first case
      to be described in a pre-existing lymphangioma circumscriptum. During a follow-up
      of 9 years, the lymphangioma circumscriptum has recurred, but there has been no
      evidence of DT recurrence or metastasis.

PMID- 18095999
TI  - Acne inversa complicated by squamous cell carcinoma in association with diffuse
      malignant peritoneal mesothelioma arising in the absence of predisposing factors:
      a case report.
AB  - Diffuse malignant peritoneal mesothelioma (DMPM) is a relatively rare neoplasm.
      Risk factors associated with its development include asbestos exposure, chronic
      irritation or inflammation of the peritoneum, abdominal radiotherapy, familial
      Mediterranean fever and simian virus 40. A familial segregation of this neoplasia
      has been reported in small villages of the Cappadocian region of Turkey, and it
      has been postulated that hereditary factors may predispose to mesothelioma, even
      with exposure to small amounts of asbestos. We report a case of DMPM, which
      apparently occurred in the absence of predisposing factors in a patient with a
      clinical history characterized by recurrent pre-sacral acne inversa of long
      duration. The association of this chronic inflammatory disease with DMPM has
      never been reported. The genetic locus for acne inversa has recently been
      identified within the 1p21.1-1q25.3 chromosomal region. Interestingly, frequent
      losses in chromosomal region 1p.21-22 have been found in mesothelioma as well. It
      is thus tempting to speculate that genetic mutations involving chromosome 1p.21
      22 may account for the development of both diseases.

PMID- 18096001
TI  - Transverse sectioning of the scalp (Headington technique) in the 19th century.
AB  - A review of the history of microscopy shows a period of intense amateur as well
      as professional interest in light microscopy in the 19th century. In order to
      accommodate these activities, there developed a group of people who prepared high
      quality microscopic slides. These slides covered a range of specimens including
      diatoms, insects, plants, rocks as well as animal and human tissues. Two slides
      of human scalp that were prepared in the latter half of the 19th century recently
      became available. They were processed to show both vertically and transversely
      sectioned skin. The slide of transversely sectioned skin contained two levels,
      one in the subcutis and the other in the mid-dermis. These slides are very
      similar to the slides that are prepared today for the evaluation of alopecia. It
      is interesting that slide preparers of the 19th century were using methods
      similar to those that were pioneered by Dr Headington but not for the evaluation
      of hair diseases. Rather they came to a similar method of preparation to
      maximally display the normal morphology of the hair of the scalp.

PMID- 18096000
TI  - Terbinafine-induced dermatomyositis: a case report and literature review of drug
      induced dermatomyositis.
AB  - Dermatomyositis, a connective tissue disease syndrome where antibodies to the
      endothelium of the microvasculature of the skin, muscle and lung are implicated
      in lesional propagation, is characterized by photodistributed erythema,
      heliotrope rash, Gottron's papules, muscle weakness and interstitial pulmonary
      fibrosis. Endotheliotropic viruses and underlying neoplasia are among the
      inciting triggers. Uncommon drugs, namely the lipid-lowering agents, have been
      implicated in dermatomyositis. The patient, a 57-year-old man, developed a
      photodistributed rash and muscle weakness following treatment with the antifungal
      medication, terbinafine. A skin biopsy was performed, showing an atrophying
      interface dermatitis with pandermal mucinosis and striking vasculopathic changes
      including endothelial cell necrosis with denudement and basement membrane zone
      reduplication. Ultrastructural studies confirmed the presence of endothelial cell
      injury. Direct immunofluorescent testing showed prominent staining of C5b-9 along
      the dermal-epidermal junction and within the vasculature. Western blot studies
      showed strong seroreactivity of his serum to an endothelial-based protein
      weighing 45,000, a common target described in other microvascular injury-based
      syndromes. We have shown a temporal association between use of terbinafine and
      the development of dermatomyositis. The exact basis remains speculative. One
      potential hypothesis is based on the fact that terbinafine, the active agent in
      terbinafine, triggers apoptosis of human endothelial cells in culture. Enhanced
      endothelial cell apoptosis results in the displacement of various cellular
      antigens creating a state of neoantigenicity; its attendant sequelae is held to
      be one of anti-endothelial cell antibody formation, a defining pathogenetic event
      in the evolution of dermatomyositis. The second may be because of the effects of
      the drug on the promotion of an interferon-rich T-helper-1-dominant cytokine
      milieu.

PMID- 18096002
TI  - CD99 - much ado about nothing?

PMID- 18096003
TI  - Comment on the 'histological evolution of lentiginous melanoma'.

PMID- 18096006
TI  - Monitoring of indirect allorecognition: wishful thinking or solid data?
AB  - Monitoring of T cells involved in the alloimmune response after transplantation
      requires the availability of reliable in vitro assays for the detection of T
      cells with both direct and indirect allospecificity. While generally accepted
      assays exist to measure helper and cytotoxic T cells involved in direct
      allorecognition, consensus about an assay for monitoring indirect T-cell
      allorecognition in clinical transplantation is lacking. Many studies claim a
      relationship between the reactivity of T cells with indirect allospecificity and
      graft rejection, but different protocols are used and essential controls are
      often lacking. In this review, the disadvantages and pitfalls of the current
      approaches are discussed, in some cases supported by the results of our own in
      vitro experiments. We conclude that an international workshop is necessary to
      establish and validate a uniform, robust and reliable assay for the monitoring of
      transplant recipients and to study the actual role of indirect allorecognition in
      acute and chronic rejection.

PMID- 18096007
TI  - A primer on peer review.

PMID- 18096008
TI  - Parents' concerns about issues related to their children's genetic conditions.
AB  - PURPOSE: The purpose of this analysis was to examine parents' (N = 142) concerns
      about issues (i.e., privacy of information, insurance, healthcare costs,
      employment, school) related to their children's genetic conditions. DESIGN AND
      METHODS: Using a series of matrices, thematic analysis was conducted focusing on
      parents' concerns. RESULTS: Parents were less concerned with privacy and more
      concerned with insurance, healthcare costs, employment, and school issues.
      PRACTICE IMPLICATIONS: Nurses and other healthcare professionals need to give
      parents the opportunity to discuss their concerns and to assist parents with
      strategies and resources to meet the needs of their children and families.

PMID- 18096009
TI  - Association of adolescent physical and emotional health with perceived severity
      of parental substance abuse.
AB  - PURPOSE: This study aims to examine the association between adolescent health,
      including physical complaints, mood, and social adjustment, and perceived
      severity of parental substance abuse. DESIGN AND METHODS: Baseline data from a
      study of school-based support groups for adolescents with substance-abusing
      family members (n = 121) were used to examine the relationship between the
      severity of substance abuse and adolescent health. RESULTS: Participants were
      divided into three groups on the basis of severity of parental substance abuse.
      The high-severity group had significantly more medical conditions, physical
      symptoms, and negative moods than those in the low- or moderate-severity groups
      (p < .02). PRACTICE IMPLICATIONS: Nurses can use the Children of Alcoholics
      Screening Tool to assess severity of parental substance abuse and its impact on
      adolescents' physical and emotional health.

PMID- 18096010
TI  - Managing the caseload: a qualitative action research study exploring how
      community children's nurses deliver services to children living with life
      limiting, life-threatening, and chronic conditions.
AB  - PURPOSE; The number of children living with life-limiting, life-threatening, and
      chronic conditions nursed at home/in the community is increasing. There is
      limited literature on how community children's nurses (CCNs) manage their
      caseloads. DESIGN AND METHODS: A qualitative-action research study used in-depth
      interviews. RESULTS: The study generated a number of insights about the sorts of
      phenomena that contribute to CCNs' perceptions of workload. Themes included
      strategy, being proactive, purposeful visit, and knowing families. PRACTICE
      IMPLICATIONS: Using a workload tool may help CCNs manage caseloads. Further work
      in other areas is required to identify issues of cultural specificity.

PMID- 18096012
TI  - Acetaminophen dosing for neonates, infants, and children.

PMID- 18096011
TI  - Investigating time to void after lower-extremity orthopedic surgery in a
      pediatric population.
AB  - PURPOSE: This study aims to determine the time frame of postoperative bladder
      volume assessment in order to identify children at risk for urinary retention in
      a pediatric orthopedic population. DESIGN AND METHODS: This is a descriptive and
      nonexperimental study. Variables included age, sex, length of anesthesia, type of
      analgesia, analgesia delivery, bladder volume, and intravenous fluid rate.
      RESULTS: Twenty-nine percent of the children (n = 38) required straight
      catheterization. The average length of time to bladder emptying was 5 hr. There
      were significant correlations (p < .05) between several variables. PRACTICE
      IMPLICATIONS: The standard practice of waiting 8 hr before assessment of voiding
      was not supported in this study.

PMID- 18096013
TI  - Extended parent-child separations: impact on substance-abusing Hispanic
      adolescents.

PMID- 18096014
TI  - Partnering for health education: pairing clinical students with school nurses.

PMID- 18096015
TI  - Build or buy? Using surveys in clinical research.

PMID- 18096016
TI  - Expression of functional Bacillus SpoIISAB toxin-antitoxin modules in Escherichia
      coli.
AB  - SpoIISA and SpoIISB proteins from Bacillus subtilis belong to a recently
      described bacterial programmed-cell death system. The current work demonstrates
      that the toxin-antitoxin module is also functional in Escherichia coli cells,
      where the expression of SpoIISA toxin leads to transient growth arrest coupled
      with cell lysis, and SpoIISA-induced death can be prevented by coexpression of
      its cognate antitoxin, SpoIISB. Escherichia coli cells appear to be able to
      escape the SpoIISA killing by activation of a specific, as yet unidentified
      protease that cleaves out the cytosolic part of the protein. Analysis of the
      toxic effects of the transmembrane and cytosolic portions of SpoIISA showed that
      neither of them separately can function as a toxin; therefore, both parts of the
      protein have to act in concert to exert the killing. This work also identifies
      genes encoding putative homologues of SpoIISA and SpoIISB proteins on chromosomes
      of other Bacilli species. The SpoIISA-like proteins from Bacillus anthracis and
      Bacillus cereus were shown to manifest the same effect on the viability of E.
      coli as their homologue from B. subtilis. Moreover, expression of the proposed
      spoIISB-like gene rescues E. coli cells from death induced by the SpoIISA
      homologue.

PMID- 18096017
TI  - Isolation and characterization of a novel Enterococcus faecalis bacteriophage
      phiEF24C as a therapeutic candidate.
AB  - Vancomycin-resistant Enterococcus faecalis (VRE) has become a significant threat
      in nosocomial settings. Bacteriophage (phage) therapy is frequently proposed as a
      potential alternative therapy for infections caused by this bacterium. To search
      for candidate therapeutic phages against Enterococcus faecalis infections, 30
      Enterococcus faecalis phages were isolated from the environment. One of these,
      virulent phage phiEF24C, which has a broad host range, was selected for analysis.
      The plaque-forming ability of phiEF24C was virtually unaffected by differences in
      the clinical host strains. Furthermore, the phage had a shorter latent period and
      a larger burst size than ordinary tailed phages, indicating that phiEF24C has
      effective lytic activity against many Enterococcus faecalis strains, including
      VRE. Morphological and genomic analyses revealed that phiEF24C is a large
      myovirus (classified as family Myoviridae morphotype A1) with a linear double
      stranded DNA genome of c. 143 kbp. Analyses of the N-terminal amino acid
      sequences of the virion proteins, together with the morphology and the genome
      size, speculated that phiEF24C is closely related to other myoviruses of Gram
      positive bacteria that have been used experimentally or practically for therapy
      or prophylaxis. Considering these results, phiEF24C may be a potential candidate
      therapeutic phage against Enterococcus faecalis infections.

PMID- 18096018
TI  - Integron-bearing methicillin-resistant coagulase-negative staphylococci in South
      China, 2001-2004.
AB  - A total of 53 methicillin-resistant coagulase-negative staphylococci strains
      isolated in a hospital in Guangzhou, China, were analyzed to detect class 1
      integrons and SCCmec typing. Thirty strains had the class 1 integrase (intI1)
      gene and 26 strains possessed the 3' conserved region of qacEDelta1-sul1. Four
      different types of gene cassette arrays were found and a highly prevalent array
      of dfrA12-orfF-aadA2 gene cassettes was observed. Thirty class 1 integron
      positive coagulase-negative staphylococci strains were subjected to Southern
      hybridization analysis; the result showed that class 1 integrons were located on
      chromosome, not plasmid. According to the results of SCCmec typing for 30
      integron-bearing MRCNS strains, five, 15 and five strains belonged to type I, II
      and III SCCmec, respectively, and five strains were untypeable. For 23 non
      integron-bearing methicillin-resistant coagulase-negative staphylococci strains,
      four, nine and seven strains belonged to type I, II and III SCCmec, respectively,
      and three strains were untypeable. None of the strains belonged to type IV or V.
      Twenty-three coagulase-negative staphylococci isolates of three Staphylococcal
      species that contained the dfrA12-orfF-aadA2 gene cassette array were
      phylogenetically unrelated to each other by randomly amplified polymorphic DNA,
      indicating that the gene cassettes might be disseminated in the clinical strains
      by a horizontal gene transfer.

PMID- 18096019
TI  - Expression of in vivo-inducible Salmonella enterica promoters during infection of
      Caenorhabditis elegans.
AB  - In vitro mimicking of the stimuli controlling in vivo-inducible bacterial
      promoters during infection of the host can be complex. Therefore, the use of the
      nematode Caenorhabditis elegans was evaluated, as a surrogate host to examine the
      expression of Salmonella enterica promoters. Green fluorescent protein (GFP+) was
      put under the control of the promoters of the pagC, mgtB, sseA, pgtE and fur
      genes of S. enterica. After infection of C. elegans with an S. enterica serovar
      Typhimurium vaccine strain expressing these constructs, clear bacterial
      expression of GFP+ was observed under the control of all five promoters, although
      significant expression was not always obtained in vitro. It is concluded that C.
      elegans constitutes a useful model system for the study of the in vivo expression
      of Salmonella promoters.

PMID- 18096020
TI  - Molecular characterization of benzimidazole-resistant isolates of Cladosporium
      fulvum.
AB  - The benzimidazole fungicide thiophanate-methyl is commonly applied to control
      leaf mould of tomato caused by Cladosporium fulvum in China. In this study, 32
      isolates of C. fulvum were examined for their sensitivities to thiophanate
      methyl, and two benzimidazole-resistant (BenR) phenotypes BenR1 and BenR2 were
      identified. The BenR1 isolates were resistant to thiophanate-methyl, but were
      more sensitive to the phenylcarbamate fungicide diethofencarb than the wild-type
      isolates. The BenR2 isolates resistant to thiophanate-methyl were insensitive to
      diethofencarb. All tested isolates were sensitive to the dicarboximide fungicide
      iprodione. The complete beta-tubulin gene was isolated from this fungus to study
      its potential role in benzimidazole resistance. Analysis of the DNA sequence of
      the beta-tubulin gene showed that the BenR1 isolates had a point mutation at
      codon 198, causing a substitution of glutamic acid to alanine. In the BenR2
      isolates, a point mutation at codon 200 causing a substitution of phenylalanine
      to tyrosine was detected. Based on these point mutations, a multiplex allele
      specific PCR method was developed successfully for the first time to detect two
      point mutations at the beta-tubulin gene simultaneously in single PCR
      amplifications.

PMID- 18096021
TI  - An AraC/XylS family transcriptional regulator homologue from Bacteroides fragilis
      is associated with cell survival following DNA damage.
AB  - A putative transcriptional regulator of the AraC/XylS family was identified in a
      genomic genebank of Bacteroides fragilis Bf-1, which partially relieved the
      sensitivity of Escherichia coli DNA repair mutants to the DNA-damaging agents,
      metronidazole and mitomycin C. A homologue of this gene with the same phenotype
      was identified as BF638R3281 in B. fragilis 638R. Transcription of BF638R3281 was
      constitutive with respect to exposure to sublethal doses of metronidazole.
      BF638R3281 was interrupted by single cross-over gene-specific insertion mutation,
      and the gene disruption was confirmed by PCR and DNA-sequencing analysis. The
      mutant grew more slowly than the wild type, and the mutation rendered B. fragilis
      more sensitive to metronidazole and mitomycin C. This indicates that the
      BF638R3281 gene product plays a role in the survival of B. fragilis following DNA
      damage by these agents.

PMID- 18096022
TI  - Bath-related headache and topiramate.

PMID- 18096024
TI  - Re: Transtentorial herniation with cerebral infarction and duret haemorrhage in a
      patient with spontaneous intracranial hypotension.

PMID- 18096025
TI  - Airplane headache: a neurologist's personal experience.

PMID- 18096026
TI  - Affective psychosis, Hashimoto's thyroiditis, and brain perfusion abnormalities:
      case report.
AB  - BACKGROUND: It has recently become evident that circulating thyroid antibodies
      are found in excess among patients suffering from mood disorders. Moreover, a
      manic episode associated with Hashimoto's thyroiditis has recently been reported
      as the first case of bipolar disorder due to Hashimoto's encephalopathy. We
      report a case in which Hashimoto's thyroiditis was suspected to be involved in
      the deteriorating course of mood disorder and discuss potential pathogenic
      mechanisms linking thyroid autoimmunity with psychopathology. CASE PRESENTATION:
      A 43-year-old woman, with a history of recurrent depression since the age of 31,
      developed manic, psychotic, and soft neurological symptoms across the last three
      years in concomitance with her first diagnosis of Hashimoto's thyroiditis. The
      patient underwent a thorough medical and neurological workup. Circulating
      thyroperoxidase antibodies were highly elevated but thyroid function was
      adequately maintained with L-thyroxine substitution. EEG was normal and no other
      signs of current CNS inflammation were evidenced. However, brain magnetic
      resonance imaging evidenced several non-active lesions in the white matter from
      both hemispheres, suggestive of a non-specific past vasculitis. Brain single
      photon emission computed tomography showed cortical perfusion asymmetry
      particularly between frontal lobes. CONCLUSION: We hypothesize that abnormalities
      in cortical perfusion might represent a pathogenic link between thyroid
      autoimmunity and mood disorders, and that the rare cases of severe Hashimoto's
      encephalopathy presenting with mood disorder might be only the tip of an iceberg.

PMID- 18096027
TI  - Identifying the most suitable endogenous control for determining gene expression
      in hearts from organ donors.
AB  - BACKGROUND: Quantitative real-time reverse transcription PCR (qRT-PCR) is a
      useful tool for assessing gene expression in different tissues, but the choice of
      adequate controls is critical to normalise the results, thereby avoiding
      differences and maximizing sensitivity and accuracy. So far, many genes have been
      used as a single reference gene, without having previously verified their value
      as controls. This practice can lead to incorrect conclusions and recent evidence
      indicates a need to use the geometric mean of data from several control genes.
      Here, we identified an appropriate set of genes to be used as an endogenous
      reference for quantifying gene expression in human heart tissue. RESULTS: Our
      findings indicate that out of ten commonly used reference genes (GADPH, PPIA,
      ACTB, YWHAZ, RRN18S, B2M, UBC, TBP, RPLP and HPRT), PPIA, RPLP and GADPH show the
      most stable gene transcription levels in left ventricle specimens obtained from
      organ donors, as assessed using geNorm and Normfinder software. The expression of
      TBP was found to be highly regulated. CONCLUSION: We propose the use of PPIA,
      RPLP and GADPH as reference genes for the accurate normalisation of qRT-PCR
      performed on heart tissue. TBP should not be used as a control in this type of
      tissue.

PMID- 18096029
TI  - Indigenous well-being in four countries: an application of the UNDP'S human
      development index to indigenous peoples in Australia, Canada, New Zealand, and
      the United States.
AB  - BACKGROUND: Canada, the United States, Australia, and New Zealand consistently
      place near the top of the United Nations Development Programme's Human
      Development Index (HDI) rankings, yet all have minority Indigenous populations
      with much poorer health and social conditions than non-Indigenous peoples. It is
      unclear just how the socioeconomic and health status of Indigenous peoples in
      these countries has changed in recent decades, and it remains generally unknown
      whether the overall conditions of Indigenous peoples are improving and whether
      the gaps between Indigenous peoples and other citizens have indeed narrowed.
      There is unsettling evidence that they may not have. It was the purpose of this
      study to determine how these gaps have narrowed or widened during the decade 1990
      to 2000. METHODS: Census data and life expectancy estimates from government
      sources were used to adapt the Human Development Index (HDI) to examine how the
      broad social, economic, and health status of Indigenous populations in these
      countries have changed since 1990. Three indices - life expectancy, educational
      attainment, and income - were combined into a single HDI measure. RESULTS:
      Between 1990 and 2000, the HDI scores of Indigenous peoples in North America and
      New Zealand improved at a faster rate than the general populations, closing the
      gap in human development. In Australia, the HDI scores of Indigenous peoples
      decreased while the general populations improved, widening the gap in human
      development. While these countries are considered to have high human development
      according to the UNDP, the Indigenous populations that reside within them have
      only medium levels of human development. CONCLUSION: The inconsistent progress in
      the health and well-being of Indigenous populations over time, and relative to
      non-Indigenous populations, points to the need for further efforts to improve the
      social, economic, and physical health of Indigenous peoples.

PMID- 18096028
TI  - Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer
      cells.
AB  - BACKGROUND: Ginger (Zingiber officinale Rosc) is a natural dietary component with
      antioxidant and anticarcinogenic properties. The ginger component [6]-gingerol
      has been shown to exert anti-inflammatory effects through mediation of NF-kappaB.
      NF-kappaB can be constitutively activated in epithelial ovarian cancer cells and
      may contribute towards increased transcription and translation of angiogenic
      factors. In the present study, we investigated the effect of ginger on tumor cell
      growth and modulation of angiogenic factors in ovarian cancer cells in vitro.
      METHODS: The effect of ginger and the major ginger components on cell growth was
      determined in a panel of epithelial ovarian cancer cell lines. Activation of NF
      kappaB and and production of VEGF and IL-8 was determined in the presence or
      absence of ginger. RESULTS: Ginger treatment of cultured ovarian cancer cells
      induced profound growth inhibition in all cell lines tested. We found that in
      vitro, 6-shogaol is the most active of the individual ginger components tested.
      Ginger treatment resulted in inhibition of NF-kB activation as well as diminished
      secretion of VEGF and IL-8. CONCLUSION: Ginger inhibits growth and modulates
      secretion of angiogenic factors in ovarian cancer cells. The use of dietary
      agents such as ginger may have potential in the treatment and prevention of
      ovarian cancer.

PMID- 18096030
TI  - Preparedness of emergency departments in northwest England for managing chemical
      incidents: a structured interview survey.
AB  - BACKGROUND: A number of significant chemical incidents occur in the UK each year
      and may require Emergency Departments (EDs) to receive and manage contaminated
      casualties. Previously UK EDs have been found to be under-prepared for this, but
      since October 2005 acute hospital Trusts have had a statutory responsibility to
      maintain decontamination capacity. We aimed to evaluate the level of preparedness
      of Emergency Departments in North West England for managing chemical incidents.
      METHODS: A face-to-face semi-structured interview was carried out with the Nurse
      Manager or a nominated deputy in all 18 Emergency Departments in the Region.
      RESULTS: 16/18 departments had a written chemical incident plan but only 7 had
      the plan available at interview. All had a designated decontamination area but
      only 11 felt that they were adequately equipped. 12/18 had a current training
      programme for chemical incident management and 3 had no staff trained in
      decontamination. 13/18 could contain contaminated water from casualty
      decontamination and 6 could provide shelter for casualties before
      decontamination. CONCLUSION: We have identified major inconsistencies in the
      preparedness of North West Emergency Departments for managing chemical incidents.
      Nationally recognized standards on incident planning, facilities, equipment and
      procedures need to be agreed and implemented with adequate resources. Issues of
      environmental safety and patient dignity and comfort should also be addressed.

PMID- 18096031
TI  - Quantitative comparison of DNA detection by GFP-lac repressor tagging,
      fluorescence in situ hybridization and immunostaining.
AB  - BACKGROUND: GFP-fusion proteins and immunostaining are methods broadly applied to
      investigate the three-dimensional organization of cells and cell nuclei, the
      latter often studied in addition by fluorescence in situ hybridization (FISH).
      Direct comparisons of these detection methods are scarce, however. RESULTS: We
      provide a quantitative comparison of all three approaches. We make use of a cell
      line that contains a transgene array of lac operator repeats which are detected
      by GFP-lac repressor fusion proteins. Thus we can detect the same structure in
      individual cells by GFP fluorescence, by antibodies against GFP and by FISH with
      a probe against the transgene array. Anti-GFP antibody detection was repeated
      after FISH. Our results show that while all four signals obtained from a
      transgene array generally showed qualitative and quantitative similarity, they
      also differed in details. CONCLUSION: Each of the tested methods revealed
      particular strengths and weaknesses, which should be considered when interpreting
      respective experimental results. Despite the required denaturation step, FISH
      signals in structurally preserved cells show a surprising similarity to signals
      generated before denaturation.

PMID- 18096033
TI  - Large-scale ruthenium- and enzyme-catalyzed dynamic kinetic resolution of (rac)-1
      phenylethanol.
AB  - The scale-up of the ruthenium- and enzyme-catalyzed dynamic kinetic resolution
      (DKR) of (rac)-1-phenylethanol (2) is addressed. The immobilized lipase Candida
      antarctica lipase B (CALB) was employed for the resolution, which shows high
      enantioselectivity in the transesterification. The ruthenium catalyst used, (eta
      5-C5Ph5)RuCl(CO)2 1, was shown to possess very high reactivity in the "in situ"
      redox racemization of 1-phenylethanol (2) in the presence of the immobilized
      enzyme, and could be used in 0.05 mol% with high efficiency. Commercially
      available isopropenyl acetate was employed as acylating agent in the lipase
      catalyzed transesterifications, which makes the purification of the product very
      easy. In a successful large-scale DKR of 2, with 0.05 mol% of 1, (R)-1
      phenylethanol acetate (3) was obtained in 159 g (97% yield) in excellent
      enantiomeric excess (99.8% ee).

PMID- 18096032
TI  - The Internet as a source of reproductive health information among adolescent
      girls in an urban city in Nigeria.
AB  - BACKGROUND: There exists some research evidence regarding how adolescents utilize
      the Internet for health information seeking purposes. The purpose of this study
      is to understand how in-school and out-of-school adolescent girls in Owerri,
      Nigeria use online resources to meet their reproductive health information needs.
      The result could be considered very crucial in assessing the potential role of
      the Internet in providing health information to adolescent girls in a typical
      Nigerian urban city. METHODS: A questionnaire was used to collect data from 1011
      adolescent girls in selected secondary schools in the communities, and also from
      134 out-of-school girls selected from the same communities. RESULTS: More than
      73% of the girls reported having ever used the Internet; more than 74% and 68% of
      them being in-school and out-of-school respectively. The in-school girls (43.9%)
      reported having home access more than the out-of-school (5.6%) although the out
      of-school have used the Internet for finding reproductive and related information
      more than the in-school. While parents (66.22%) and teachers (56.15%) are the two
      sources most used to the in-school girls, friends (63.18%) and the Internet
      (55.19%) were reported by the out-of-school youth as the two most used sources of
      information to them. CONCLUSION: The Internet is not a first choice of source of
      reproductive health information for both the in-school and out-of-school
      adolescent girls in Owerri, Nigeria. The source is however, more commonly used by
      the out-of-school than the in-school, but the in-school have a more favorable
      assessment of the quality of information they obtain from the Internet.

PMID- 18096034
TI  - Altered autonomic nervous system activity as a potential etiological factor of
      premenstrual syndrome and premenstrual dysphoric disorder.
AB  - BACKGROUND: Premenstrual syndrome (PMS) encompasses a wide variety of cyclic and
      recurrent physical, emotional, and behavioral symptoms occurring during the late
      luteal phase of the menstrual cycle and abating shortly following the beginning
      of menses. Although PMS is widely recognized, its etiopathogenesis is not yet
      understood. The present study investigates whether the activity of the autonomic
      nervous system, which plays a vital role in orchestrating physiological
      homeostasis within the human body, is altered during the menstrual cycle of women
      with different degrees of premenstrual symptomatology. METHODS: Sixty-two women
      in their 20s to 40s with regular menstrual cycles participated in this study. All
      subjects were examined during the follicular and late luteal phases. Cycle phase
      was determined by the onset of menstruation and oral temperature and was verified
      by concentrations of ovarian hormones, estrone, and pregnanediol in a urine
      sample taken early in the morning. Autonomic nervous system activity was assessed
      by means of heart-rate variability (HRV) power spectral analysis during supine
      rest. The Menstrual Distress Questionnaire was used to evaluate physical,
      emotional, and behavioral symptoms accompanying the menstrual cycle of the
      subjects. The subjects were categorized in three groups, Control, PMS, and
      premenstrual dysphoric disorder (PMDD) groups, depending on the severity of
      premenstrual symptomatology. RESULTS: No intramenstrual cycle difference in any
      of the parameters of HRV was found in the Control group, which had no or a small
      increase in premenstrual symptoms. In contrast, Total power and high frequency
      power, which reflect overall autonomic and parasympathetic nerve activity,
      respectively, significantly decreased in the late luteal phase from the
      follicular phase in the PMS group. As for the PMDD group, which had more severe
      symptoms premenstrually, heart-rate fluctuation as well as all components of the
      power spectrum of HRV were markedly decreased regardless of the menstrual cycle
      compared to those of the other two groups. CONCLUSION: Several theories have been
      proposed to explain the underlying mechanisms of PMS with its complex web of bio
      psycho-social factors. Although causes and consequences continue to elude, the
      present study provides intriguing and novel findings that the altered functioning
      of the autonomic nervous system in the late luteal phase could be associated with
      diverse psychosomatic and behavioral symptoms appearing premenstrually. In
      addition, when symptoms become more severe (as seen in women with PMDD), the
      sympathovagal function might be more depressed regardless of the menstrual cycle.

PMID- 18096035
TI  - GC-MS studies of the chemical composition of two inedible mushrooms of the genus
      Agaricus.
AB  - BACKGROUND: Mushrooms in the genus Agaricus have worldwide distribution and
      include the economically important species A. bisporus. Some Agaricus species are
      inedible, including A. placomyces and A. pseudopratensis, which are similar in
      appearance to certain edible species, yet are known to possess unpleasant odours
      and induce gastrointestinal problems if consumed. We have studied the chemical
      composition of these mushrooms using GC-MS. RESULTS: Our GC-MS studies on the
      volatile fractions and butanol extracts resulted in the identification of 44 and
      34 compounds for A. placomyces and A. pseudopratensis, respectively, including
      fatty acids and their esters, amino acids, and sugar alcohols. The most abundant
      constituent in the volatiles and butanol were phenol and urea respectively. We
      also identified the presence of ergosterol and two Delta7-sterols. In addition,
      5alpha,8alpha-Epidioxi-24(xi)-methylcholesta-6,22-diene-3beta-ol was isolated for
      the first time from both mushrooms. Our study is therefore the first report on
      the chemical composition of these two species. CONCLUSION: The results obtained
      contribute to the knowledge of the chemical composition of mushrooms belonging to
      the Agaricus genus, and provide some explanation for the reported mild toxicity
      of A. placomyces and A. pseudopratensis, a phenonomenon that can be explained by
      a high phenol content, similar to that found in other Xanthodermatei species.

PMID- 18096036
TI  - AphanoDB: a genomic resource for Aphanomyces pathogens.
AB  - BACKGROUND: The Oomycete genus Aphanomyces comprises devastating plant and animal
      pathogens. However, little is known about the molecular mechanisms underlying
      pathogenicity of Aphanomyces species. In this study, we report on the development
      of a public database called AphanoDB which is dedicated to Aphanomyces genomic
      data. As a first step, a large collection of Expressed Sequence Tags was obtained
      from the legume pathogen A. euteiches, which was then processed and collected
      into AphanoDB. DESCRIPTION: Two cDNA libraries of A. euteiches were created: one
      from mycelium growing on synthetic medium and one from mycelium grown in contact
      to root tissues of the model legume Medicago truncatula. From these libraries,
      18,684 expressed sequence tags were obtained and assembled into 7,977 unigenes
      which were compared to public databases for annotation. Queries on AphanoDB allow
      the users to retrieve information for each unigene including similarity to known
      protein sequences, protein domains and Gene Ontology classification. Statistical
      analysis of EST frequency from the two different growth conditions was also added
      to the database. CONCLUSION: AphanoDB is a public database with a user-friendly
      web interface. The sequence report pages are the main web interface which
      provides all annotation details for each unigene. These interactive sequence
      report pages are easily available through text, BLAST, Gene Ontology and
      expression profile search utilities. AphanoDB is available from URL:
      http://www.polebio.scsv.ups-tlse.fr/aphano/.

PMID- 18096037
TI  - The venom gland transcriptome of the Desert Massasauga rattlesnake (Sistrurus
      catenatus edwardsii): towards an understanding of venom composition among
      advanced snakes (Superfamily Colubroidea).
AB  - BACKGROUND: Snake venoms are complex mixtures of pharmacologically active
      proteins and peptides which belong to a small number of superfamilies. Global
      cataloguing of the venom transcriptome facilitates the identification of new
      families of toxins as well as helps in understanding the evolution of venom
      proteomes. RESULTS: We have constructed a cDNA library of the venom gland of a
      threatened rattlesnake (a pitviper), Sistrurus catenatus edwardsii (Desert
      Massasauga), and sequenced 576 ESTs. Our results demonstrate a high abundance of
      serine proteinase and metalloproteinase transcripts, indicating that the
      disruption of hemostasis is a principle mechanism of action of the venom. In
      addition to the transcripts encoding common venom proteins, we detected two
      varieties of low abundance unique transcripts in the library; these encode for
      three-finger toxins and a novel toxin possibly generated from the fusion of two
      genes. We also observed polyadenylated ribosomal RNAs in the venom gland library,
      an interesting preliminary obsevation of this unusual phenomenon in a reptilian
      system. CONCLUSION: The three-finger toxins are characteristic of most elapid
      venoms but are rare in viperid venoms. We detected several ESTs encoding this
      group of toxins in this study. We also observed the presence of a transcript
      encoding a fused protein of two well-characterized toxins (Kunitz/BPTI and
      Waprins), and this is the first report of this kind of fusion in a snake toxin
      transcriptome. We propose that these new venom proteins may have ancillary
      functions for envenomation. The presence of a fused toxin indicates that in
      addition to gene duplication and accelerated evolution, exon shuffling or
      transcriptional splicing may also contribute to generating the diversity of
      toxins and toxin isoforms observed among snake venoms. The detection of low
      abundance toxins, as observed in this and other studies, indicates a greater
      compositional similarity of venoms (though potency will differ) among advanced
      snakes than has been previously recognized.

PMID- 18096038
TI  - Boussignac continuous positive airway pressure for the management of acute
      cardiogenic pulmonary edema: prospective study with a retrospective control
      group.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) treatment for acute
      cardiogenic pulmonary edema can have important benefits in acute cardiac care.
      However, coronary care units are usually not equipped and their personnel not
      adequately trained for applying CPAP with mechanical ventilators. Therefore we
      investigated in the coronary care unit setting the feasibility and outcome of the
      simple Boussignac mask-CPAP (BCPAP) system that does not need a mechanical
      ventilator. METHODS: BCPAP was introduced in a coronary care unit where staff had
      no CPAP experience. All consecutive patients transported to our hospital with
      acute cardiogenic pulmonary edema, a respiratory rate > 25 breaths/min and a
      peripheral arterial oxygen saturation of < 95% while receiving oxygen, were
      included in a prospective BCPAP group that was compared with a historical control
      group that received conventional treatment with oxygen alone. RESULTS: During the
      2-year prospective BCPAP study period 108 patients were admitted with acute
      cardiogenic pulmonary edema. Eighty-four of these patients (78%) were treated at
      the coronary care unit of which 66 (61%) were treated with BCPAP. During the
      control period 66 patients were admitted over a 1-year period of whom 31 (47%)
      needed respiratory support in the intensive care unit. BCPAP treatment was
      associated with a reduced hospital length of stay and fewer transfers to the
      intensive care unit for intubation and mechanical ventilation. Overall estimated
      savings of approximately euro 3,800 per patient were achieved with the BCPAP
      strategy compared to conventional treatment. CONCLUSION: At the coronary care
      unit, BCPAP was feasible, medically effective, and cost-effective in the
      treatment of acute cardiogenic pulmonary edema. Endpoints included mortality,
      coronary care unit and hospital length of stay, need of ventilatory support, and
      cost (savings).

PMID- 18096039
TI  - CONTRAST: a discriminative, phylogeny-free approach to multiple informant de novo
      gene prediction.
AB  - We describe CONTRAST, a gene predictor which directly incorporates information
      from multiple alignments rather than employing phylogenetic models. This is
      accomplished through the use of discriminative machine learning techniques,
      including a novel training algorithm. We use a two-stage approach, in which a set
      of binary classifiers designed to recognize coding region boundaries is combined
      with a global model of gene structure. CONTRAST predicts exact coding region
      structures for 65% more human genes than the previous state-of-the-art method,
      misses 46% fewer exons and displays comparable gains in specificity.

PMID- 18096040
TI  - Sticky knowledge: a possible model for investigating implementation in healthcare
      contexts.
AB  - BACKGROUND: In health care, a well recognized gap exists between what we know
      should be done based on accumulated evidence and what we actually do in practice.
      A body of empirical literature shows organizations, like individuals, are
      difficult to change. In the business literature, knowledge management and
      transfer has become an established area of theory and practice, whilst in
      healthcare it is only starting to establish a firm footing. Knowledge has become
      a business resource, and knowledge management theorists and practitioners have
      examined how knowledge moves in organisations, how it is shared, and how the
      return on knowledge capital can be maximised to create competitive advantage. New
      models are being considered, and we wanted to explore the applicability of one of
      these conceptual models to the implementation of evidence-based practice in
      healthcare systems. METHODS: The application of a conceptual model called sticky
      knowledge, based on an integration of communication theory and knowledge transfer
      milestones, into a scenario of attempting knowledge transfer in primary care.
      RESULTS: We describe Szulanski's model, the empirical work he conducted, and
      illustrate its potential applicability with a hypothetical healthcare example
      based on improving palliative care services. We follow a doctor through two
      different posts and analyse aspects of knowledge transfer in different primary
      care settings. The factors included in the sticky knowledge model include: causal
      ambiguity, unproven knowledge, motivation of source, credibility of source,
      recipient motivation, recipient absorptive capacity, recipient retentive
      capacity, barren organisational context, and arduous relationship between source
      and recipient. We found that we could apply all these factors to the difficulty
      of implementing new knowledge into practice in primary care settings. DISCUSSION:
      Szulanski argues that knowledge factors play a greater role in the success or
      failure of a knowledge transfer than has been suspected, and we consider that
      this conjecture requires further empirical work in healthcare settings.

PMID- 18096041
TI  - A randomized physiotherapy trial in patients with fecal incontinence: design of
      the PhysioFIT-study.
AB  - BACKGROUND: Fecal incontinence (FI) is defined as the recurrent involuntary
      excretion of feces in inappropriate places or at inappropriate times. It is a
      major and highly embarrassing health care problem which affects about 2 to 24% of
      the adult population. The prevalence increases with age in both men and women.
      Physiotherapy interventions are often considered a first-line approach due to its
      safe and non-invasive nature when dietary and pharmaceutical treatment fails or
      in addition to this treatment regime. Two physiotherapy interventions, rectal
      balloon training (RBT) and pelvic floor muscle training (PFMT) are widely used in
      the management of FI. However, their effectiveness remains uncertain since well
      designed trials on the effectiveness of RBT and PFMT versus PFMT alone in FI have
      never been published. METHODS/DESIGN: A two-armed randomized controlled clinical
      trial will be conducted. One hundred and six patients are randomized to receive
      either PFMT combined with RBT or PFMT alone. Physicians in the University
      Hospital Maastricht include eligible participants. Inclusion criteria are (1)
      adults (aged > or = 18 years), (2) with fecal incontinence complaints due to
      different etiologies persisting for at least six months, (3) having a Vaizey
      incontinence score of at least 12, (4) and failure of conservative treatment
      (including dietary adaptations and pharmacological agents). Baseline measurements
      consist of the Vaizey incontinence score, medical history, physical examination,
      medication use, anorectal manometry, rectal capacity measurement, anorectal
      sensation, anal endosonography, defecography, symptom diary, Fecal Incontinence
      Quality of Life scale (FIQL) and the PREFAB-score. Follow-up measurements are
      scheduled at three, six and 12 months after inclusion. Skilled and registered
      physiotherapists experienced in women's health perform physiotherapy treatment.
      Twelve sessions are administered during three months according to a standardized
      protocol. DISCUSSION: This section discusses the decision to publish a trial
      protocol, the actions taken to minimize bias and confounding in the design,
      explains the choice for two treatment groups, discusses the secondary goals of
      this study and indicates the impact of this trial on clinical practice. TRIAL
      REGISTRATION: The Netherlands Trial Register ISRCTN78640169.

PMID- 18096042
TI  - The Hall Technique; a randomized controlled clinical trial of a novel method of
      managing carious primary molars in general dental practice: acceptability of the
      technique and outcomes at 23 months.
AB  - BACKGROUND: Scotland has high levels of untreated dental caries in primary teeth.
      The Hall Technique is a simplified method of managing carious primary molars
      using preformed metal crowns (PMCs) cemented with no local anaesthesia, caries
      removal or tooth preparation. This study compared the acceptability of the Hall
      Technique for children, their carers, and dentists, and clinical outcomes for the
      technique, with conventional restorations. METHODS: General dental practice
      based, split mouth, randomized controlled trial (132 children, aged 3-10).
      General dental practitioners (GDPs, n = 17) in Tayside, Scotland (dmft 2.7)
      placed conventional (Control) restorations in carious primary molars, and Hall
      Technique PMCs on the contralateral molar (matched clinically and
      radiographically). Dentists ranked the degree of discomfort they felt the child
      experienced for each procedure; then children, their carers and dentists stated
      which technique they preferred. The teeth were followed up clinically and
      radiographically. RESULTS: 128 conventional restorations were placed on 132
      control teeth, and 128 PMCs on 132 intervention teeth. Using a 5 point scale, 118
      Hall PMCs (89%) were rated as no apparent discomfort up to mild, not significant;
      for Control restorations the figure was 103 (78%). Significant, unacceptable
      discomfort was recorded for two Hall PMCs (1.5%) and six Control restorations
      (4.5%). 77% of children, 83% of carers and 81% of dentists who expressed a
      preference, preferred the Hall technique, and this was significant (Chi square, p
      < 0.0001). There were 124 children (94% of the initial sample) with a minimum
      follow-up of 23 months. The Hall PMCs outperformed the Control restorations:a)
      'Major' failures (signs and symptoms of irreversible pulpal disease): 19 Control
      restorations (15%); three Hall PMCs (2%) (P < 0.000);b) 'Minor' failures (loss of
      restoration, caries progression): 57 Control restorations (46%); six Hall PMCs
      (5%) (P < 0.000)c) Pain: 13 Control restorations (11%); two Hall PMCs (2%) (P =
      0.003). CONCLUSION: The Hall Technique was preferred to conventional restorations
      by the majority of children, carers and GDPs. After two years, Hall PMCs showed
      more favourable outcomes for pulpal health and restoration longevity than
      conventional restorations. The Hall Technique appears to offer an effective
      treatment option for carious primary molar teeth. TRIAL REGISTRATION NUMBER:
      Current Controlled Trials ISRCTN47267892 - A randomized controlled trial in
      primary care of a novel method of using preformed metal crowns to manage decay in
      primary molar teeth: the Hall technique.

PMID- 18096043
TI  - Functional characterization of two novel 5' untranslated exons reveals a complex
      regulation of NOD2 protein expression.
AB  - BACKGROUND: NOD2 is an innate immune receptor for the bacterial cell wall
      component muramyl-dipeptide. Mutations in the leucine-rich repeat region of NOD2,
      which lead to an impaired recognition of muramyl-dipeptide, have been associated
      with Crohn disease, a human chronic inflammatory bowel disease. Tissue specific
      constitutive and inducible expression patterns of NOD2 have been described that
      result from complex regulatory events for which the molecular mechanisms are not
      yet fully understood. RESULTS: We have identified two novel exons of the NOD2
      gene (designated exon 1a and 1b), which are spliced to the canonical exon 2 and
      constitute the 5' untranslated region of two alternative transcript isoforms
      (i.e. exon 1a/1b/2 and exon 1a/2). The two novel transcripts are abundantly
      expressed and seem to comprise the majority of NOD2 transcripts under
      physiological conditions. We confirm the expression of the previously known
      canonical first exon (designated exon 1c) of the gene in unstimulated mononuclear
      cells. The inclusion of the second alternative exon 1b, which harbours three
      short upstream open reading frames (uORFs), is downregulated upon stimulation
      with TNF-alpha or under pro-inflammatory conditions in the inflamed intestinal
      mucosa in vivo. Using the different 5' UTR splice forms fused to a firefly
      luciferase (LUC) reporter we demonstrate a rapamycin-sensitive inhibitory effect
      of the uORFs on translation efficacy. CONCLUSION: The differential usage of two
      alternative promoters in the NOD2 gene leads to tissue-specific and context
      dependent NOD2 transcript isoform patterns. We demonstrate for the first time
      that context-dependent alternative splicing is linked to uORF-mediated
      translational repression. The results suggest complex parallel control mechanisms
      that independently regulate NOD2 expression in the context of inflammatory
      signaling.

PMID- 18096044
TI  - The fungus Ustilago maydis and humans share disease-related proteins that are not
      found in Saccharomyces cerevisiae.
AB  - BACKGROUND: The corn smut fungus Ustilago maydis is a well-established model
      system for molecular phytopathology. In addition, it recently became evident that
      U. maydis and humans share proteins and cellular processes that are not found in
      the standard fungal model Saccharomyces cerevisiae. This prompted us to do a
      comparative analysis of the predicted proteome of U. maydis, S. cerevisiae and
      humans. RESULTS: At a cut off at 20% identity over protein length, all three
      organisms share 1738 proteins, whereas both fungi share only 541 conserved
      proteins. Despite the evolutionary distance between U. maydis and humans, 777
      proteins were shared. When applying a more stringent criterion (> or = 20%
      identity with a homologue in one organism over at least 50 amino acids and > or =
      10% less in the other organism), we found 681 proteins for the comparison of U.
      maydis and humans, whereas the both fungi share only 622 fungal specific
      proteins. Finally, we found that S. cerevisiae and humans shared 312 proteins. In
      the U. maydis to H. sapiens homology set 454 proteins are functionally classified
      and 42 proteins are related to serious human diseases. However, a large portion
      of 222 proteins are of unknown function. CONCLUSION: The fungus U. maydis has a
      long history of being a model system for understanding DNA recombination and
      repair, as well as molecular plant pathology. The identification of functionally
      un-characterized genes that are conserved in humans and U. maydis opens the door
      for experimental work, which promises new insight in the cell biology of the
      mammalian cell.

PMID- 18096045
TI  - A new approach of nonparametric estimation of incidence and lifetime risk based
      on birth rates and incident events.
AB  - BACKGROUND: Incidence and lifetime risk of diabetes are important public health
      measures. Traditionally, nonparametric estimates are obtained from survey data by
      means of a Nelson-Aalen estimator which requires data information on both
      incident events and risk sets from the entire cohort. Such data information is
      rarely available in real studies. METHODS: We compare two different approaches
      for obtaining nonparametric estimates of age-specific incidence and lifetime risk
      with emphasis on required assumptions. The first and novel approach only
      considers incident cases occurring within a fixed time window-we have termed this
      cohort-of-cases data-which is linked explicitly to the birth process in the past.
      The second approach is the usual Nelson-Aalen estimate which requires knowledge
      on observed time at risk for the entire cohort and their incident events. Both
      approaches are used on data on anti-diabetic medications obtained from Odense
      Pharmacoepidemiological Database, which covers a population of approximately
      470,000 over the period 1993-2003. For both methods we investigate if and how
      incidence rates can be projected. RESULTS: Both the new and standard method yield
      similar sigmoidal shaped estimates of the cumulative distribution function of age
      specific incidence. The Nelson-Aalen estimator gives somewhat higher estimates of
      lifetime risk (15.65% (15.14%; 16.16%) for females, and 17.91% (17.38%; 18.44%)
      for males) than the estimate based on cohort-of-cases data (13.77% (13.74%;
      13.81%) for females, 15.61% (15.58%; 15.65%) for males). Accordingly the
      projected incidence rates are higher based on the Nelson-Aalen estimate-also too
      high when compared to observed rates. In contrast, the cohort-of-cases approach
      gives projections that fit observed rates better. CONCLUSION: The developed
      methodology for analysis of cohort-of-cases data has potential to become a cost
      effective alternative to a traditional survey based study of incidence. To allow
      more general use of the methodology, more research is needed on how to relax
      stationarity assumptions.

PMID- 18096046
TI  - Assessment of precision and reproducibility of a new myograph.
AB  - BACKGROUND: The physiological characteristics of muscle activity and the
      assessment of muscle strength represent important diagnostic information. There
      are many devices that measure muscle force in humans, but some require voluntary
      contractions, which are difficult to assess in weak or unconscious patients who
      are unable to complete a full range of voluntary force assessment tasks. Other
      devices, which obtain standard muscle contractions by electric stimulations, do
      not have the technology required to induce and measure reproducible valid
      contractions at the optimum muscle length. METHODS: In our study we used a newly
      developed diagnostic device which measures accurately the reproducibility and
      time-changed-variability of the muscle force in an individual muscle. A total of
      500 in-vivo measurements of supra-maximal isometric single twitch contractions
      were carried out on the musculus adductor pollicis of 5 test subjects over 10
      sessions, with ten repetitions per session. The same protocol was performed on
      405 test subjects with two repetitions each to determine a reference-interval on
      healthy subjects. RESULTS: Using our test setting, we found a high
      reproducibility of the muscle contractions of each test subject. The precision of
      the measurements performed with our device was 98.74%. Only two consecutive
      measurements are needed in order to assess a real, representative individual
      value of muscle force. The mean value of the force of contraction was 9.51 N and
      the 95% reference interval was 4.77-14.25 N. CONCLUSION: The new myograph is a
      highly reliable measuring device with which the adductor pollicis can be
      investigated at the optimum length. It has the potential to become a reliable and
      valid tool for diagnostic in the clinical setting and for monitoring
      neuromuscular diseases.

PMID- 18096047
TI  - Characterization and simulation of cDNA microarray spots using a novel
      mathematical model.
AB  - BACKGROUND: The quality of cDNA microarray data is crucial for expanding its
      application to other research areas, such as the study of gene regulatory
      networks. Despite the fact that a number of algorithms have been suggested to
      increase the accuracy of microarray gene expression data, it is necessary to
      obtain reliable microarray images by improving wet-lab experiments. As the first
      step of a cDNA microarray experiment, spotting cDNA probes is critical to
      determining the quality of spot images. RESULTS: We developed a governing
      equation of cDNA deposition during evaporation of a drop in the microarray
      spotting process. The governing equation included four parameters: the surface
      site density on the support, the extrapolated equilibrium constant for the
      binding of cDNA molecules with surface sites on glass slides, the macromolecular
      interaction factor, and the volume constant of a drop of cDNA solution. We
      simulated cDNA deposition from the single model equation by varying the value of
      the parameters. The morphology of the resulting cDNA deposit can be classified
      into three types: a doughnut shape, a peak shape, and a volcano shape. The spot
      morphology can be changed into a flat shape by varying the experimental
      conditions while considering the parameters of the governing equation of cDNA
      deposition. The four parameters were estimated by fitting the governing equation
      to the real microarray images. With the results of the simulation and the
      parameter estimation, the phenomenon of the formation of cDNA deposits in each
      type was investigated. CONCLUSION: This study explains how various spot shapes
      can exist and suggests which parameters are to be adjusted for obtaining a good
      spot. This system is able to explore the cDNA microarray spotting process in a
      predictable, manageable and descriptive manner. We hope it can provide a way to
      predict the incidents that can occur during a real cDNA microarray experiment,
      and produce useful data for several research applications involving cDNA
      microarrays.

PMID- 18096049
TI  - Deep vein thrombosis and pulmonary embolus associated with a ruptured popliteal
      aneurysm - a cautionary note.
AB  - Popliteal artery aneurysms representing 80% of peripheral artery aneurysms
      rarely rupture (a reported incidence of 0.1-2.8 %) and second commonest in
      frequency after aorto-iliac aneurysms. They usually present with pain, swelling,
      occlusion or distal embolisation and can cause diagnostic difficulties. We report
      a 78 year old man who was previously admitted to hospital with a pulmonary
      embolus secondary to deep venous thrombosis. He was heparinized then warfarinised
      and was readmitted with a ruptured popliteal aneurysm leading to a large pseudo
      aneurysm formation. The pulmonary embolus had been due to popliteal vein
      thrombosis and propagation of the clot. A thorough review of literature
      identified only one previously reported case of ruptured popliteal artery
      aneurysm and subsequent large pseudo aneurysm formation. We feel it is important
      to exclude a popliteal aneurysm in a patient with DVT. This may be more common
      than the published literature suggests.

PMID- 18096048
TI  - Regulation of heme oxygenase-1 mRNA deadenylation and turnover in NIH3T3 cells by
      nitrosative or alkylation stress.
AB  - BACKGROUND: Heme oxygenase-1 (HO-1) catalizes heme degradation, and is considered
      one of the most sensitive indicators of cellular stress. Previous work in human
      fibroblasts has shown that HO-1 expression is induced by NO, and that
      transcriptional induction is only partially responsible; instead, the HO-1 mRNA
      half-life is substantially increased in response to NO. The mechanism of this
      stabilization remains unknown. RESULTS: In NIH3T3 murine fibroblasts, NO exposure
      increased the half-life of the HO-1 transcript from ~1.6 h to 11 h, while
      treatments with CdCl2, NaAsO2 or H2O2 increased the half-life only up to 5 h.
      Although poly(A) tail shortening can be rate-limiting in mRNA degradation, the HO
      1 mRNA deadenylation rate in NO-treated cells was ~65% of that in untreated
      controls. In untreated cells, HO-1 poly(A) removal proceeded until 30-50 nt
      remained, followed by rapid mRNA decay. In NO-treated cells, HO-1 deadenylation
      stopped with the mRNA retaining poly(A) tails 30-50 nt long. We hypothesize that
      NO treatment stops poly(A) tail shortening at the critical 30- to 50-nt length.
      This is not a general mechanism for the post-transcriptional regulation of HO-1
      mRNA. Methyl methane sulfonate also stabilized HO-1 mRNA, but that was associated
      with an 8-fold decrease in the deadenylation rate compared to that of untreated
      cells. Another HO-1 inducer, CdCl2, caused a strong increase in the mRNA level
      without affecting the HO-1 mRNA half-life. CONCLUSION: The regulation of HO-1
      mRNA levels in response to cellular stress can be induced by transcriptional and
      different post-transcriptional events that act independently, and vary depending
      on the stress inducer. While NO appears to stabilize HO-1 mRNA by preventing the
      final steps of deadenylation, methyl methane sulfonate achieves stabilization
      through the regulation of earlier stages of deadenylation.

PMID- 18096050
TI  - INvestigational Vertebroplasty Efficacy and Safety Trial (INVEST): a randomized
      controlled trial of percutaneous vertebroplasty.
AB  - BACKGROUND: The treatment of painful osteoporotic vertebral compression fractures
      has historically been limited to several weeks of bed rest, anti-inflammatory and
      analgesic medications, calcitonin injections, or external bracing. Percutaneous
      vertebroplasty (the injection of bone cement into the fractured vertebral body)
      is a relatively new procedure used to treat these fractures. There is increasing
      interest to examine the efficacy and safety of percutaneous vertebroplasty and to
      study the possibility of a placebo effect or whether the pain relief is from
      local anesthetics placed directly on the bone during the vertebroplasty
      procedure. METHODS/DESIGNS: Our goal is to test the hypothesis that patients with
      painful osteoporotic vertebral compression fractures who undergo vertebroplasty
      have less disability and pain at 1 month than patients who undergo a control
      intervention. The control intervention is placement of local anesthesia near the
      fracture, without placement of cement. One hundred sixty-six patients with
      painful osteoporotic vertebral compression fractures will be recruited over 5
      years from US and foreign sites performing the vertebroplasty procedure. We will
      exclude patients with malignant tumor deposit (multiple myeloma), tumor mass or
      tumor extension into the epidural space at the level of the fracture. We will
      randomly assign participants to receive either vertebroplasty or the control
      intervention. Subjects will complete a battery of validated, standardized
      measures of pain, functional disability, and health related quality of life at
      baseline and at post-randomization time points (days 1, 2, 3, and 14, and months
      1, 3, 6, and 12). Both subjects and research interviewers performing the follow
      up assessments will be blinded to the randomization assignment. Subjects will
      have a clinic visit at months 1 and 12. Spine X-rays will be obtained at the end
      of the study (month 12) to determine subsequent fracture rates. Our co-primary
      outcomes are the modified Roland score and pain numerical rating scale at 1
      month. DISCUSSION: Although extensively utilized throughout North America for
      palliation of pain, vertebroplasty still has not undergone rigorous study. The
      study outlined above represents the first randomized, controlled study that can
      account for a placebo effect in the setting of vertebroplasty. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN81871888.

PMID- 18096051
TI  - Improved functional expression of recombinant human ether-a-go-go (hERG) K+
      channels by cultivation at reduced temperature.
AB  - BACKGROUND: HERG potassium channel blockade is the major cause for drug-induced
      long QT syndrome, which sometimes cause cardiac disrhythmias and sudden death.
      There is a strong interest in the pharmaceutical industry to develop high quality
      medium to high-throughput assays for detecting compounds with potential cardiac
      liability at the earliest stages of drug development. Cultivation of cells at
      lower temperature has been used to improve the folding and membrane localization
      of trafficking defective hERG mutant proteins. The objective of this study was to
      investigate the effect of lower temperature maintenance on wild type hERG
      expression and assay performance. RESULTS: Wild type hERG was stably expressed in
      CHO-K1 cells, with the majority of channel protein being located in the
      cytoplasm, but relatively little on the cell surface. Expression at both
      locations was increased several-fold by cultivation at lower growth temperatures.
      Intracellular hERG protein levels were highest at 27 degrees C and this
      correlated with maximal 3H-dofetilide binding activity. In contrast, the
      expression of functionally active cell surface-associated hERG measured by patch
      clamp electrophysiology was optimal at 30 degrees C. The majority of the
      cytoplasmic hERG protein was associated with the membranes of cytoplasmic
      vesicles, which markedly increased in quantity and size at lower temperatures or
      in the presence of the Ca2+-ATPase inhibitor, thapsigargin. Incubation with the
      endocytic trafficking blocker, nocodazole, led to an increase in hERG activity at
      37 degrees C, but not at 30 degrees C. CONCLUSION: Our results are consistent
      with the concept that maintenance of cells at reduced temperature can be used to
      boost the functional expression of difficult-to-express membrane proteins and
      improve the quality of assays for medium to high-throughput compound screening.
      In addition, these results shed some light on the trafficking of hERG protein
      under these growth conditions.

PMID- 18096052
TI  - Post-translational modifications of histones H3 and H4 associated with the
      histone methyltransferases Suv39h1 and G9a.
AB  - Specific combinations of post-translational modifications of histones alter
      chromatin structure, facilitating gene transcription or silencing. Here we have
      investigated the 'histone code' associated with the histone methyltransferases
      Suv39h1 and G9a by combining double immunopurification and mass spectrometry. Our
      results confirm the previously reported histone modifications associated with
      Suv39h1 and G9a. Moreover, this method allowed us to demonstrate for the first
      time an association of acetylated histones with the repressor proteins Suv39h1
      and G9a.

PMID- 18096053
TI  - Testing for homogeneity of gametic disequilibrium across strata.
AB  - BACKGROUND: Assessing the non-random associations of alleles at different loci,
      or gametic disequilibrium, can provide clues about aspects of population
      histories and mating behavior and can be useful in locating disease genes. For
      gametic data which are available from several strata with different allele
      probabilities, it is necessary to verify that the strata are homogeneous in terms
      of gametic disequilibrium. RESULTS: Using the likelihood score theory generalized
      to nuisance parameters we derive a score test for homogeneity of gametic
      disequilibrium across several independent populations. Simulation results
      demonstrate that the empirical type I error rates of our score homogeneity test
      perform satisfactorily in the sense that they are close to the pre-chosen 0.05
      nominal level. The associated power and sample size formulae are derived. We
      illustrate our test with a data set from a study of the cystic fibrosis
      transmembrane conductance regulator gene. CONCLUSION: We propose a large-sample
      homogeneity test on gametic disequilibrium across several independent populations
      based on the likelihood score theory generalized to nuisance parameters. Our
      simulation results show that our test is more reliable than the traditional test
      based on the Fisher's test of homogeneity among correlation coefficients.

PMID- 18096054
TI  - Association between the -455T>C promoter polymorphism of the APOC3 gene and the
      metabolic syndrome in a multi-ethnic sample.
AB  - BACKGROUND: Common polymorphisms in the promoter of the APOC3 gene have been
      associated with hypertriglyceridemia and may impact on phenotypic expression of
      the metabolic syndrome (MetS). The rs7566605 marker, located near the INSIG2
      gene, has been found to be associated with obesity, making it also a potential
      genetic determinant for MetS. The objective of this study is to examine the APOC3
      -455T>C and the INSIG2 rs7566605 polymorphisms as potential genetic determinants
      for MetS in a multi-ethnic sample. METHODS: Subjects were genotyped for both the
      APOC3 -455T>C and INSIG2 rs7566605 polymorphisms, and classified for the presence
      or absence of MetS (NCEP ATP III and IDF definitions). The total study population
      included 2675 subjects (> or =18 years of age) from six different geographical
      ancestries. RESULTS: For the overall study population, the prevalence of MetS was
      22.6% (NCEP ATP III definition). Carriers of > or =1 copy of APOC3 -455C were
      more likely to have MetS (NCEP ATP III definition) than noncarriers (carrier odds
      ratio 1.73, 95% CI 1.40 to 2.14, adjusting for age and study group). The basis of
      the association was related not only to a higher proportion of -455C carriers
      meeting the triglyceride and high-density lipoprotein cholesterol criteria, but
      also the blood pressure criteria compared with wild-type homozygotes. Plasma apo
      C-III concentrations were not associated with APOC3 -455T>C genotype. The INSIG2
      rs7566605 polymorphism was not associated with MetS or measures of obesity.
      CONCLUSION: Meta-analysis of the sample of multiple geographic ancestries
      indicated that the functional -455T>C promoter polymorphism in APOC3 was
      associated with an approximately 2-fold increased risk of MetS, whereas the
      INSIG2 rs7566605 polymorphism was not associated with MetS.

PMID- 18096055
TI  - The views of stakeholders on controlled access schemes for high-cost
      antirheumatic biological medicines in Australia.
AB  - BACKGROUND: In Australia, government-subsidised access to high-cost medicines is
      "targeted" to particular sub-sets of patients under the Pharmaceutical Benefits
      Scheme to achieve cost-effective use. In order to determine how this access
      system could be improved, the opinions of key stakeholders on access to
      biological agents for rheumatoid arthritis were explored. METHODS: Thirty-six
      semi-structured interviews were conducted with persons from relevant stakeholder
      groups. These were transcribed verbatim, and analysed thematically. RESULTS:
      Controlled access to expensive medicines was considered to be equitable and
      practical; however, there was disagreement as to the method of defining the
      target patient populations. Other concerns included timeliness of access,
      excessive bureaucracy, and the need for additional resources to facilitate the
      scheme. Collaboration between stakeholders was deemed important because it allows
      more equitable distribution of limited resources. The majority considered that
      stakeholder consultation should have been broader. Most wanted increased
      transparency of the decision-making process, ongoing and timely review of access
      criteria, and an increased provision of information for patients. More structured
      communication between stakeholders was proposed. CONCLUSION: The Pharmaceutical
      Benefit Scheme is adapting to meet the changing needs of patients. Provision of
      subsidised access to high-cost medicines in a manner that is affordable for
      individuals and society, and that is equitable and efficiently managed is
      challenging. The views of stakeholders on targeted access to anti-rheumatic
      biological medicines in Australia acknowledged this challenge and provided a
      number of suggestions for modifications. These could serve as a basis to inform
      the debate on how to change the processes and policies so as to improve the
      scheme.

PMID- 18096056
TI  - Bilateral cytomegalovirus (CMV) oophoritis mimicking widely metastatic carcinoma:
      a case report and review of the literature.
AB  - Ovarian cytomegalovirus (CMV) infection is a rare finding reported in autopsy
      studies of immunocompromised patients. We report the first case of bilateral CMV
      oophoritis diagnosed in surgical resection specimens from a 63-year-old woman
      with metastatic brain lesions undergoing whole brain radiation and steroid
      treatment. The ovarian involvement of CMV infection was an incidental finding
      during the colectomy and bilateral salpingo-oophorectomy procedure for
      gastrointestinal bleeding and presumed ovarian metastases. In contrast to the
      prevailing dogma, a review of the literature found similar prevalence of pre
      menopausal and post-menopausal cases. While age related vasculopathy was thought
      to be the prevailing mechanism for CMV oophoritis, the observation of an
      inflammation mediated microthrombosis in our case provides a plausible age
      independent mechanism suggesting that both restrictive and obstructive vascular
      changes can be involved in the pathogenesis of CMV oophoritis. To avoid
      misdiagnosis, both pathologists and clinicians should recognize ovarian
      involvement by CMV as a possibility in the immunocompromised patient.

PMID- 18096058
TI  - Incidence and clinicopathologic features of gastrointestinal stromal tumors. A
      population-based study.
AB  - BACKGROUND: Although the diagnostic criteria and pathogenesis of gastrointestinal
      stromal tumors (GIST) have recently been elucidated, knowledge of the
      epidemiology of this malignancy is still limited. This study examined the
      incidence of GIST in the province of Modena, including pathologic features and
      clinical outcome. METHODS: Gastrointestinal mesenchymal tumors identified by the
      Modena Cancer Registry between 1991 and 2004 were analyzed with an
      immunohistochemical panel that included staining for CD-117 and PDGFRalpha. Size,
      mitotic rate, and other pathologic parameters were recorded. Each tumor was
      categorized into National Institutes of Health risk categories (very low, low,
      intermediate, and high risk). RESULTS: One hundred twenty-four cases were
      classified as GIST. The age-adjusted incidence rate was 6.6 per million. Seventy
      five percent of patients were symptomatic; 34% had a previous or concomitant
      history of cancer. High-risk features were present in 47% of cases. Seventy-eight
      percent were submitted to radical surgery. After complete resection, the 5-year
      disease-free survival rates were 94%, 92%, 100%, and 40% for patients at very
      low, low, intermediate, and high risk, respectively. In multivariate analysis,
      high risk was the main predictor of recurrence. CONCLUSION: This population-based
      study shows that the incidence of GIST in Northern Italy is comparable to that
      reported in other European countries. Survival was favorable in lower risk
      categories and in most of the resected cases. In our study, resected patients at
      very low, low, and intermediate risk had a similar outcome. Our data support the
      need to consider high-risk patients after complete surgical resection for
      treatment with the best available approach.

PMID- 18096057
TI  - The presence of beta2-adrenoceptors sensitizes alpha2A-adrenoceptors to
      desensitization after chronic epinephrine treatment.
AB  - BACKGROUND: In addition to the regulation of blood pressure, alpha2- and beta
      adrenoceptor (AR) subtypes play an important role in the modulation of
      noradrenergic neurotransmission in the human CNS and PNS. Several studies suggest
      that the alpha2-AR responsiveness in cells and tissues after chronic epinephrine
      (EPI) or norepinephrine (NE) exposure may vary, depending on the beta-AR activity
      present there. Recently, we reported that in BE(2)-C human neuroblastoma cells
      (endogenously expressing alpha2A- and beta2-AR), chronic EPI treatment (300 nM)
      produced a dramatic beta-adrenoceptor-dependent desensitization of the alpha2A-AR
      response. The aim of this study is to determine if stable addition of a beta2-AR
      to a second neuroblastoma cell line (SH-SY5Y), that normally expresses only
      alpha2A-ARs that are not sensitive to 300 nM EPI exposure, would suddenly render
      alpha2A-ARs in that cell line sensitive to treatment with the same EPI
      concentration. METHODS: These studies employed RT-PCR, receptor binding and
      inhibition of cAMP accumulation to confirm alpha2-AR subtype expression. Stable
      clones of SH-SY5Y cells transfected to stably express functional beta2-ARs
      (SHbeta2AR4) were selected to compare sensitivity of alpha2-AR to EPI in the
      presence or absence of beta2-ARs. RESULTS: A series of molecular, biochemical and
      pharmacological studies indicated that the difference between the cell lines
      could not be attributed to alpha2-AR heterogeneity. We now report that after
      transfection of functional beta2-AR into SH-SY5Y cells (SHbeta2AR4), chronic
      treatment with modest levels of EPI desensitizes the alpha2A-AR. This effect
      results from a beta2-AR dependent down-regulation of native alpha2A-ARs by EPI
      accompanied by enhanced translocation of GRK2 and GRK3 to the membrane (required
      for GRK-mediated phosphorylation of agonist-occupied receptors). CONCLUSION: This
      study further supports the hypothesis that the presence of the beta-AR renders
      the alpha2A-AR more susceptible to desensitization with physiological levels of
      EPI.

PMID- 18096059
TI  - Phase I dose escalation study of vinorelbine and topotecan combination
      chemotherapy in patients with recurrent lung cancer.
AB  - BACKGROUND: A platinum doublet is the current standard treatment for good
      performance status patients with advanced non-small cell lung cancer (NSCLC) and
      extensive stage small cell lung cancer (SCLC) with good performance status.
      However, platinum-based treatment may be associated with significant toxicities,
      therefore alternative platinum-free combinations should be investigated.
      Topotecan is a topoisomerase I inhibitor that exerts its cytotoxic effect through
      stabilization of the topoisomerase I-DNA complex. Preclinical data suggests
      synergy between topoisomerase I inhibitors and mitotic spindle poisons.
      Considerable hematologic toxicities have been reported with topotecan dosed for 5
      consecutive days in combination with vinorelbine. Therefore, the aim of this
      study was to evaluate the optimal dosage and the maximal tolerated dose (MTD) of
      topotecan and vinorelbine in patients with relapsed or refractory non-small cell
      or small cell lung cancer administered on an alternate dosing schedule. METHODS:
      From February, 2004 to March, 2007 eighteen patients with advanced or recurrent
      NSCLC or SCLC previously treated with chemotherapy were enrolled. Patients were
      heavily pretreated with 22% having received at least 3 prior lines of
      chemotherapy. Vinorelbine was administered at a fixed dose (20 mg/m2) and
      topotecan at escalating doses (2, 2.5, 3, 3.5, and 4 mg/m2) on days 1 and 8 every
      21 days. RESULTS: The MTD was not reached in any of the 5 cohorts, with only one
      dose limiting toxicity (DLT) occurring in cohort 4. Non-hematological toxicities
      were manageable. One patient had a partial response with four patients (27%)
      achieving stable disease. The median progression-free and overall survival for
      all patients, were 2.7 months (95% CI: 1.6, 9.1) and 10.5 months (95% CI: 4.2,
      22.7), respectively. CONCLUSION: Vinorelbine and topotecan administered on days 1
      and 8 every 21 days is well tolerated without any DLT seen with previously
      investigated topotecan schedules. This doublet provides a potentially active non
      platinum containing doublet for the treatment of patients with advanced SCLC and
      NSCLC. Vinorelbine and topotecan should therefore be investigated in subsequent
      phase II studies at a dose of 20 mg/m2 and 4 mg/m2, respectively. TRIAL
      REGISTRATION NUMBER: NCT00287963.

PMID- 18096060
TI  - Cytoplasmic location of factor-inhibiting hypoxia-inducible factor is associated
      with an enhanced hypoxic response and a shorter survival in invasive breast
      cancer.
AB  - INTRODUCTION: Hypoxia-inducible factor (HIF)-1alpha levels in invasive breast
      carcinoma have been shown to be an adverse prognostic indicator. Cellular HIF
      1alpha activity is regulated by factor-inhibiting hypoxia-inducible factor 1 (FIH
      1). In hypoxia, FIH-1 hydroxylation of Asn803 within the C-terminal
      transactivation domain does not occur and HIF-1alpha forms a fully active
      transcriptional complex. The present study investigates the role of FIH-1 in
      invasive breast carcinoma and its correlation with hypoxia. METHODS: Microarrayed
      tissue cores from 295 invasive carcinomas were stained for FIH-1, for HIF-1alpha
      and for carbonic anhydrase 9. FIH-1 expression was correlated with standard
      clinicopathological parameters and with the expression of the surrogate hypoxic
      markers HIF-1alpha and carbonic anhydrase 9. RESULTS: FIH-1 was positive in
      239/295 (81%) tumours, 42/295 (14%) exclusively in the nucleus and 54/295 (18%)
      exclusively in the cytoplasm. Exclusive nuclear FIH-1 expression was
      significantly inversely associated with tumour grade (P = 0.02) and risk of
      recurrence (P = 0.04), whereas exclusive cytoplasmic FIH-1 was significantly
      positively associated with tumour grade (P = 0.004) and carbonic anhydrase 9
      expression (P = 0.02). Patients with tumours that excluded FIH-1 from the nucleus
      had a significantly shorter survival compared with those with exclusive nuclear
      expression (P = 0.02). Cytoplasmic FIH-1 expression was also an independent poor
      prognostic factor for disease-free survival. CONCLUSION: FIH-1 is widely
      expressed in invasive breast carcinoma. As with other HIF regulators, its
      association between cellular compartmentalization and the hypoxic response and
      survival suggests that tumour regulation of FIH-1 is an additional important
      mechanism for HIF pathway activation.

PMID- 18096061
TI  - Sequencing analysis of 20,000 full-length cDNA clones from cassava reveals
      lineage specific expansions in gene families related to stress response.
AB  - BACKGROUND: Cassava, an allotetraploid known for its remarkable tolerance to
      abiotic stresses is an important source of energy for humans and animals and a
      raw material for many industrial processes. A full-length cDNA library of cassava
      plants under normal, heat, drought, aluminum and post harvest physiological
      deterioration conditions was built; 19968 clones were sequence-characterized
      using expressed sequence tags (ESTs). RESULTS: The ESTs were assembled into 6355
      contigs and 9026 singletons that were further grouped into 10577 scaffolds; we
      found 4621 new cassava sequences and 1521 sequences with no significant
      similarity to plant protein databases. Transcripts of 7796 distinct genes were
      captured and we were able to assign a functional classification to 78% of them
      while finding more than half of the enzymes annotated in metabolic pathways in
      Arabidopsis. The annotation of sequences that were not paired to transcripts of
      other species included many stress-related functional categories showing that our
      library is enriched with stress-induced genes. Finally, we detected 230 putative
      gene duplications that include key enzymes in reactive oxygen species signaling
      pathways and could play a role in cassava stress response features. CONCLUSION:
      The cassava full-length cDNA library here presented contains transcripts of genes
      involved in stress response as well as genes important for different areas of
      cassava research. This library will be an important resource for gene discovery,
      characterization and cloning; in the near future it will aid the annotation of
      the cassava genome.

PMID- 18096062
TI  - Outcome and quality of life after surgically treated ankle fractures in patients
      65 years or older.
AB  - BACKGROUND: Despite high incidence of ankle fractures in the elderly, studies
      evaluating outcome and impact of quality of life in this age group specifically
      are sparse. The aim of this study was to evaluate outcome and quality of life 6
      and 12 months after injury in patients 65 years or older who had been operated on
      due to an ankle fracture. METHODS: Sixty patients 65 years or older were invited
      to participate in the study. 6 and 12 months after the injury a questionnaire
      including inquiry to participate, the Olerud-Molander Ankle Score (OMAS), Short
      Form 36 (SF-36), Linear Analogue Scale (LAS), Self-rated Ankle Function and some
      supplementary questions was sent home to the patients. The supplementary
      questions concerned subjective experience of ankle instability, sporting and
      physical activity level before injury and recaptured activity level at follow
      ups, need of walking aid before injury, state of living before injury and at
      follow-ups and co-morbidities. After the 12-month follow-up the patients were
      also called for a radiological examination. RESULTS: Fifty patients (83%)
      answered the questionnaire at 6-month and 46 (77%) at the 12-month follow-up.
      Although, 45 (90%) fractures were low-energy trauma 44 (88%) were bi- or
      trimalleolar and post-operative reduction results were complete in 23 (46%)
      ankles. The median OMAS improved from 60 (Interquartile range (IQR) 36) at 6
      month to 70 (IQR 35) at 12-month (p = 0.002), but at 12-month still sixty percent
      or more of the patients reported pain, swelling, problems when stair-climbing and
      reduced activities of daily life. Twenty (40%) rated their ankle function as
      'good' or 'very good' at 6-month and 30 (60%) at 12-month. Forty-one (82%) were
      physically active before injury but still one year after only 18/41 had returned
      to their pre-injury physical activity level. According to SF-36 four dimensions
      differed from the age- and gender matched normative data of the Swedish
      population, 'physical function', 'role physical' and 'role emotional' were below
      norms at 6-month for women (p = 0.010, p = 0.024 and 0.031) and 'general health'
      was above norms at 12-month for men (p = 0.044). CONCLUSION: One year after
      surgically treated ankle fractures a majority of patients continue to have
      symptoms and reported functional limitations. However, SF-36 scores indicate that
      only females had functional status below the age- and gender matched normative
      data of the Swedish population.

PMID- 18096063
TI  - Age-related compaction of lens fibers affects the structure and optical
      properties of rabbit lenses.
AB  - BACKGROUND: The goal of this investigation was to correlate particular age
      related structural changes (compaction) to the amount of scatter in rabbit lenses
      and to determine if significant fiber compaction occurred in the nuclear and
      inner cortical regions. METHODS: New Zealand White rabbits at 16-20 months old
      (adult; n = 10) and at 3.5-4 years old (aged; n = 10) were utilized for this
      study. Immediately after euthanising, scatter was assessed in fresh lenses by low
      power helium-neon laser scan analysis. Scatter data was analyzed both for whole
      lenses and regionally, to facilitate correlation with morphometric data. After
      functional analysis, lenses were fixed and processed for scanning electron
      microcopy (SEM; right eyes) and light microscopy (LM; left eyes). Morphometric
      analysis of SEM images was utilized to evaluate compaction of nuclear fibers.
      Similarly, measurements from LM images were used to assess compaction of inner
      cortical fibers. RESULTS: Scatter was significantly greater in aged lenses as
      compared to adult lenses in all regions analyzed, however the difference in the
      mean was slightly more pronounced in the inner cortical region. The anterior and
      posterior elliptical angles at 1 mm (inner fetal nucleus) were significantly
      decreased in aged vs. adult lenses (anterior, p = 0.040; posterior, p = 0.036).
      However, the average elliptical angles at 2.5 mm (outer fetal nucleus) were not
      significantly different in adult and aged lenses since all lenses examined had
      comparable angles to inner fetal fibers of aged lenses, i.e. they were all
      compacted. In cortical fibers, measures of average cross-sectional fiber area
      were significantly different at diameters of both 6 and 7 mm as a function of age
      (p = 0.011 and p = 0.005, respectively). Accordingly, the estimated fiber volume
      was significantly decreased in aged as compared to adult lenses at both 6 mm
      diameter (p = 0.016) and 7 mm diameter (p = 0.010). CONCLUSION: Morphometric data
      indicates that inner cortical fibers undergo a greater degree of age-related
      compaction than nuclear fibers. Increased scatter appears to be only tentatively
      correlated with regions of fiber compaction, suggesting that it is simply one of
      an array of factors that contribute to the overall decreased transparency in aged
      rabbit lenses.

PMID- 18096064
TI  - Surface antigens and potential virulence factors from parasites detected by
      comparative genomics of perfect amino acid repeats.
AB  - BACKGROUND: Many parasitic organisms, eukaryotes as well as bacteria, possess
      surface antigens with amino acid repeats. Making up the interface between host
      and pathogen such repetitive proteins may be virulence factors involved in immune
      evasion or cytoadherence. They find immunological applications in serodiagnostics
      and vaccine development. Here we use proteins which contain perfect repeats as a
      basis for comparative genomics between parasitic and free-living organisms.
      RESULTS: We have developed Reptile http://reptile.unibe.ch, a program for
      proteome-wide probabilistic description of perfect repeats in proteins. Parasite
      proteomes exhibited a large variance regarding the proportion of repeat
      containing proteins. Interestingly, there was a good correlation between the
      percentage of highly repetitive proteins and mean protein length in parasite
      proteomes, but not at all in the proteomes of free-living eukaryotes. Reptile
      combined with programs for the prediction of transmembrane domains and GPI
      anchoring resulted in an effective tool for in silico identification of potential
      surface antigens and virulence factors from parasites. CONCLUSION: Systemic
      surveys for perfect amino acid repeats allowed basic comparisons between free
      living and parasitic organisms that were directly applicable to predict proteins
      of serological and parasitological importance. An on-line tool is available at
      http://genomics.unibe.ch/dora.

PMID- 18096065
TI  - N-methyl-D-aspartic acid (NMDA) in the nervous system of the amphioxus
      Branchiostoma lanceolatum.
AB  - BACKGROUND: NMDA (N-methyl-D-aspartic acid) is a widely known agonist for a class
      of glutamate receptors, the NMDA type. Synthetic NMDA elicits very strong
      activity for the induction of hypothalamic factors and hypophyseal hormones in
      mammals. Moreover, endogenous NMDA has been found in rat, where it has a role in
      the induction of GnRH (Gonadotropin Releasing Hormone) in the hypothalamus, and
      of LH (Luteinizing Hormone) and PRL (Prolactin) in the pituitary gland. RESULTS:
      In this study we show evidence for the occurrence of endogenous NMDA in the
      amphioxus Branchiostoma lanceolatum. A relatively high concentration of NMDA
      occurs in the nervous system of this species (3.08 +/- 0.37 nmol/g tissue in the
      nerve cord and 10.52 +/- 1.41 nmol/g tissue in the cephalic vesicle). As in rat,
      in amphioxus NMDA is also biosynthesized from D-aspartic acid (D-Asp) by a NMDA
      synthase (also called D-aspartate methyl transferase). CONCLUSION: Given the
      simplicity of the amphioxus nervous and endocrine systems compared to mammalian,
      the discovery of NMDA in this protochordate is important to gain insights into
      the role of endogenous NMDA in the nervous and endocrine systems of metazoans and
      particularly in the chordate lineage.

PMID- 18096066
TI  - EFBAT: exact family-based association tests.
AB  - BACKGROUND: Family-based association tests are important tools for investigating
      genetic risk factors of complex diseases. These tests are especially valuable for
      being robust to population structure. We introduce a tool, EFBAT, which performs
      exact family-based tests of association for X-chromosome and autosomal biallelic
      markers. RESULTS: The program EFBAT extends a network algorithm previously
      applied to autosomal markers to include the X-chromosome and to perform tests of
      association under the null hypotheses "no association, no linkage" and "no
      association in the presence of linkage" under additive, dominant and recessive
      genetic models. These tests are valid regardless of patterns of missing familial
      data. CONCLUSION: The general framework for performing exact family-based
      association tests has been usefully extended to the X-chromosome, particularly
      for the hypothesis of "no association in the presence of linkage" and for
      different genetic models.

PMID- 18096067
TI  - A unified framework of immunological and epidemiological dynamics for the spread
      of viral infections in a simple network-based population.
AB  - BACKGROUND: The desire to better understand the immuno-biology of infectious
      diseases as a broader ecological system has motivated the explicit representation
      of epidemiological processes as a function of immune system dynamics. While
      several recent and innovative contributions have explored unified models across
      cellular and organismal domains, and appear well-suited to describing particular
      aspects of intracellular pathogen infections, these existing immuno
      epidemiological models lack representation of certain cellular components and
      immunological processes needed to adequately characterize the dynamics of some
      important epidemiological contexts. Here, we complement existing models by
      presenting an alternate framework of anti-viral immune responses within
      individual hosts and infection spread across a simple network-based population.
      RESULTS: Our compartmental formulation parsimoniously demonstrates a correlation
      between immune responsiveness, network connectivity, and the natural history of
      infection in a population. It suggests that an increased disparity between
      people's ability to respond to an infection, while maintaining an average immune
      responsiveness rate, may worsen the overall impact of an outbreak within a
      population. Additionally, varying an individual's network connectivity affects
      the rate with which the population-wide viral load accumulates, but has little
      impact on the asymptotic limit in which it approaches. Whilst the clearance of a
      pathogen in a population will lower viral loads in the short-term, the longer the
      time until re-infection, the more severe an outbreak is likely to be. Given the
      eventual likelihood of reinfection, the resulting long-run viral burden after
      elimination of an infection is negligible compared to the situation in which
      infection is persistent. CONCLUSION: Future infectious disease research would
      benefit by striving to not only continue to understand the properties of an
      invading microbe, or the body's response to infections, but how these properties,
      jointly, affect the propagation of an infection throughout a population. These
      initial results offer a refinement to current immuno-epidemiological modelling
      methodology, and reinforce how coupling principles of immunology with
      epidemiology can provide insight into a multi-scaled description of an ecological
      system. Overall, we anticipate these results to as a further step towards
      articulating an integrated, more refined epidemiological theory of the reciprocal
      influences between host-pathogen interactions, epidemiological mixing, and
      disease spread.

PMID- 18096068
TI  - Internal jugular vein thrombosis in a warfarinised patient: a case report.
AB  - INTRODUCTION: Internal jugular vein thrombosis (IJVT) is a rare but potentially
      fatal condition. It usually arises following trauma to the internal jugular vein
      but is also seen in association with coagulopathies and advanced malignancies as
      part of a para-neoplastic syndrome. CASE PRESENTATION: We report a case of a 44
      year old woman with a strong past medical history and family history of
      thrombotic disease who presented with abdominal pain and ascites. A stage III
      ovarian carcinoma was diagnosed and she underwent debulking of the tumour. She
      sustained a peri-operative haemorrhage and required insertion of a central line
      into the right internal jugular vein. At one month follow-up she presented as an
      emergency with a left neck mass and painful swallowing. A duplex ultrasound of
      her neck identified a left IJVT to the level of the brachiocephalic vein which
      had occurred despite warfarinisation and an INR of greater than 2. She was
      commenced on intravenous heparin and the swelling resolved over the course of a
      week. CONCLUSION: This case illustrates an unusual presentation of a rare
      condition. In this case, the precise aetiology is unclear as the IJVT may have
      been related to a coagulopathy or the presence of advanced malignancy and
      occurred despite adequate anticoagulation.

PMID- 18096069
TI  - PCR colorimetric dot-blot assay and clinical pretest probability for diagnosis of
      Pulmonary Tuberculosis in smear-negative patients.
AB  - BACKGROUND: Smear-negative pulmonary tuberculosis (SNPTB) accounts for 30% of
      Pulmonary Tuberculosis (PTB) cases reported annually in developing nations.
      Polymerase chain reaction (PCR) may provide an alternative for the rapid
      detection of Mycobacterium tuberculosis (MTB); however little data are available
      regarding the clinical utility of PCR in SNPTB, in a setting with a high burden
      of TB/HIV co-infection. METHODS: To evaluate the performance of the PCR dot-blot
      in parallel with pretest probability (Clinical Suspicion) in patients suspected
      of having SNPTB, a prospective study of 213 individuals with clinical and
      radiological suspicion of SNPTB was carried out from May 2003 to May 2004, in a
      TB/HIV reference hospital. Respiratory specialists estimated the pretest
      probability of active disease into high, intermediate, low categories.
      Expectorated sputum was examined by direct microscopy (Ziehl-Neelsen staining),
      culture (Lowenstein Jensen) and PCR dot-blot. Gold standard was based on culture
      positivity combined with the clinical definition of PTB. RESULTS: In smear
      negative and HIV subjects, active PTB was diagnosed in 28.4% (43/151) and 42.2%
      (19/45), respectively. In the high, intermediate and low pretest probability
      categories active PTB was diagnosed in 67.4% (31/46), 24% (6/25), 7.5% (6/80),
      respectively. PCR had sensitivity of 65% (CI 95%: 50%-78%) and specificity of 83%
      (CI 95%: 75%-89%). There was no difference in the sensitivity of PCR in relation
      to HIV status. PCR sensitivity and specificity among non-previously TB treated
      and those treated in the past were, respectively: 69%, 43%, 85% and 80%. The high
      pretest probability, when used as a diagnostic test, had sensitivity of 72% (CI
      95%:57%-84%) and specificity of 86% (CI 95%:78%-92%). Using the PCR dot-blot in
      parallel with high pretest probability as a diagnostic test, sensitivity,
      specificity, positive and negative predictive values were: 90%, 71%, 75%, and
      88%, respectively. Among non-previously TB treated and HIV subjects, this
      approach had sensitivity, specificity, positive and negative predictive values of
      91%, 79%, 81%, 90%, and 90%, 65%, 72%, 88%, respectively. CONCLUSION: PCR dot
      blot associated with a high clinical suspicion may provide an important
      contribution to the diagnosis of SNPTB mainly in patients that have not been
      previously treated attended at a TB/HIV reference hospital.

PMID- 18096070
TI  - The effect of oral sodium acetate administration on plasma acetate concentration
      and acid-base state in horses.
AB  - AIM: Sodium acetate (NaAcetate) has received some attention as an alkalinizing
      agent and possible alternative energy source for the horse, however the effects
      of oral administration remain largely unknown. The present study used the
      physicochemical approach to characterize the changes in acid-base status
      occurring after oral NaAcetate/acetic acid (NAA) administration in horses.
      METHODS: Jugular venous blood was sampled from 9 exercise-conditioned horses on 2
      separate occasions, at rest and for 24 h following a competition exercise test
      (CET) designed to simulate the speed and endurance test of 3-day event.
      Immediately after the CETs horses were allowed water ad libitum and either: 1) 8
      L of a hypertonic NaAcetate/acetic acid solution via nasogastric tube followed by
      a typical hay/grain meal (NAA trial); or 2) a hay/grain meal alone (Control
      trial). RESULTS: Oral NAA resulted in a profound plasma alkalosis marked by
      decreased plasma [H+] and increased plasma [TCO2] and [HCO3-] compared to
      Control. The primary contributor to the plasma alkalosis was an increased [SID],
      as a result of increased plasma [Na+] and decreased plasma [Cl-]. An increased
      [Atot], due to increased [PP] and a sustained increase in plasma [acetate],
      contributed a minor acidifying effect. CONCLUSION: It is concluded that oral
      NaAcetate could be used as both an alkalinizing agent and an alternative energy
      source in the horse.

PMID- 18096071
TI  - Improved isolation of murine hepatocytes for in vitro malaria liver stage
      studies.
AB  - BACKGROUND: Primary hepatocyte cultures are a valuable tool for the understanding
      of cellular and molecular phenomena occurring during malaria liver stage. This
      paper describes an improved perfusion/dissociation procedure to isolate
      hepatocytes from mouse liver that is suitable for malaria studies and allows
      reproducible preparation of primary hepatocytes with consistent cell yields and
      controlled purity. RESULTS: This protocol is a detailed description of a
      technique to isolate and culture mouse hepatocytes and represents an improvement
      over previous descriptions of hepatocyte isolation for malaria studies, regarding
      three technical aspects: (1) dissociation reagents choice; (2) cell separation
      gradient and (3) cell purity control. Cell dissociation was optimized for a
      specific collagenase digestion media. The cell dissociation step was improved by
      using a three-layer discontinuous gradient. A cell purity check was introduced to
      monitor the expression of CD95 on hepatocytes using flow cytometry methods.
      CONCLUSION: The procedure described allows reproducible recovery of one to three
      million hepatocytes per preparation with cell purity of about 90% as determined
      by FACS analysis. Completion of the protocol is usually achieved in about four
      hours per preparation and pooling is suggested for multiple preparations of
      larger number of cells.

PMID- 18096072
TI  - Proximal visceral endoderm and extraembryonic ectoderm regulate the formation of
      primordial germ cell precursors.
AB  - BACKGROUND: The extraembryonic tissues, visceral endoderm (VE) and extraembryonic
      ectoderm (ExE) are known to be important for the induction of primordial germ
      cells (PGCs) in mice via activation of the bone morphogenetic protein (BMP)
      signalling pathway. We investigated whether the VE and ExE have a direct role in
      the specification of PGCs, or in an earlier event, namely the induction of the
      PGC precursors in the proximal posterior epiblast cells. RESULTS: We cultured
      embryonic day (E) 5.75 to E7.0 mouse embryos in an explant-assay with or without
      extraembryonic tissues. The reconstituted pieces of embryonic and extraembryonic
      tissues were assessed for the formation of both PGC precursors and specified
      PGCs. For this, Blimp1:gfp and Stella:gfp transgenic mouse lines were used to
      distinguish between PGC precursors and specified PGC, respectively. We observed
      that the VE regulates formation of an appropriate number of PGC precursors
      between E6.25-E7.25, but it is not essential for the subsequent specification of
      PGCs from the precursor cells. Furthermore, we show that the ExE has a different
      role from that of the VE, which is to restrict localization of PGC precursors to
      the posterior part of the embryo. CONCLUSION: We show that the VE and ExE have
      distinct roles in the induction of PGC precursors, namely the formation of a
      normal number of PGC precursors, and their appropriate localization during early
      development. However, these tissues do not have a direct role during the final
      stages of specification of the founder population of PGCs.

PMID- 18096073
TI  - The protective effect of ischemic preconditioning on rat testis.
AB  - BACKGROUND: It has been demonstrated that brief episodes of sublethal ischemia
      reperfusion, so-called ischemic preconditioning, provide powerful tissue
      protection in different tissues such as heart, brain, skeletal muscle, lung,
      liver, intestine, kidney, retina, and endothelial cells. Although a recent study
      has claimed that there are no protective effects of ischemic preconditioning in
      rat testis, the protective effects of ischemic preconditioning on testicular
      tissue have not been investigated adequately. The present study was thus planned
      to investigate whether ischemic preconditioning has a protective effect on
      testicular tissue. METHODS: Rats were divided into seven groups that each
      contained seven rats. In group 1 (control group), only unilateral testicular
      ischemia was performed by creating a testicular torsion by a 720 degree clockwise
      rotation for 180 min. In group 2, group 3, group 4, group 5, group 6, and group
      7, unilateral testicular ischemia was performed for 180 min following different
      periods of ischemic preconditioning. The ischemic preconditioning periods were as
      follows: 10 minutes of ischemia with 10 minutes of reperfusion in group 2; 20
      minutes of ischemia with 10 minutes of reperfusion in group 3; 30 minutes of
      ischemia with 10 minutes of reperfusion in group 4; multiple preconditioning
      periods were used (3 x 10 min early phase transient ischemia with 10 min
      reperfusion in all episodes) in group 5; multiple preconditioning periods were
      used (5, 10, and 15 min early phase transient ischemia with 10 min reperfusion in
      all episodes) in group 6; and, multiple preconditioning periods were used (10,
      20, and 30 min early phase transient ischemia with 10 min reperfusion in all
      episodes) in group 7. After the ischemic protocols were carried out, animals were
      sacrificed by cervical dislocation and testicular tissue samples were taken for
      biochemical measurements (protein, malondialdehyde, nitric oxide) and
      histological examination. RESULTS: Although decreased tissue malondialdehyde
      levels were detected in the groups of 2, 3, 4, and 5 compared to group 1,
      significant decreases were observed in only group 2 and group 5 (p < .05). Nitric
      oxide levels were numerically decreased in all groups compared to the control
      group but was statistically significant only in group 5 (p < .05).
      Histopathological examination demonstrated that all groups subjected to ischemic
      preconditioning had less tissue damage than group 1 (p < .05). CONCLUSION: These
      results suggest that ischemic preconditioning provides tissue protection in
      testicular tissue.

PMID- 18096074
TI  - Development and validation of the insulin treatment appraisal scale (ITAS) in
      patients with type 2 diabetes.
AB  - BACKGROUND: Timely initiation of insulin therapy in type 2 diabetes is important
      to achieve metabolic control but can be hindered by negative perceptions of
      patients regarding insulin treatment. To assess the appraisal of insulin therapy
      of persons with type 2 diabetes, we developed the insulin treatment appraisal
      scale (ITAS) and tested its reliability and validity in insulin treated type 2
      diabetes patients. METHODS: A sample of 282 patients with type 2 diabetes form
      the United States (US) completed the ITAS, the WHO-5 Well-being index (WHO-5) and
      the Problem Areas in Diabetes (PAID) Survey. Exploratory factor analysis (EFA),
      internal consistency (Cronbach's alpha) and item-total correlations were
      determined to test the reliability of the instrument. Concurrent validity was
      examined by calculating Pearson correlation coefficients between the different
      measures. Discriminant validity was examined by comparing ITAS scores of insulin
      naive and insulin using patients. RESULTS: EFA suggested a two-factor structure,
      separating positively worded and negatively worded items. Cronbach's alpha was
      0.90 for the negative appraisal scale and 0.68 for the positive appraisal scale.
      Yet, Cronbach's alpha of the total 20-item scale was 0.89, suggesting high
      homogeneity and allowing for calculation of an overall score. Item-total
      correlations were in the range of 0.46-0.74 for the negative and 0.34 - 0.53 for
      the positive appraisal scale. The item pertaining to weight gain, as part of the
      negative appraisal subscale, showed low communality and deserves further testing.
      Concurrent validity was confirmed with low to moderate correlations in the
      expected direction between ITAS and WHO-5 and PAID. Discriminant validity was
      confirmed by the fact that patients using insulin had significantly less negative
      appraisals than insulin naive patients. CONCLUSION: The ITAS is a brief,
      psychometrically sound instrument that can be used in insulin naive and insulin
      treated patients to assess positive and negative perceptions regarding insulin
      treatment and changes therein.

PMID- 18096075
TI  - Sexual selection and the evolution of obligatory sex.
AB  - BACKGROUND: Among the long-standing conundrums of evolutionary theory, obligatory
      sex is one of the hardest. Current theory suggests multiple factors that might
      explain the benefits of sex when compared with complete asexuality, but no
      satisfactory explanation for the prevalence of obligatory sex in the face of
      facultative sexual reproduction. RESULTS AND CONCLUSION: We show that when sexual
      selection is present obligatory sex can evolve and be maintained even against
      facultative sex, under common scenarios of deleterious mutations and
      environmental changes.

PMID- 18096077
TI  - A decade of clinical negligence in ophthalmology.
AB  - BACKGROUND: To present an overview of the clinical negligence claims for
      ophthalmology in the National Health Service (NHS) in England from 1995 to 2006.
      To compare ophthalmic subspecialties with respect to claim numbers and payments.
      METHODS: All the claims on the NHS Litigation Authority database for
      ophthalmology for the period 1995 to 2006 were analysed. Claims were categorised
      by ophthalmic subspecialty, and subspecialties were ranked according to numbers
      of claims, total damages paid, average level of damages and paid:closed ratio (a
      measure of the likelihood of a claim resulting in payment of damages). RESULTS:
      There were 848 claims, 651 of which were closed. 46% of closed claims resulted in
      payment of damages. The total cost of damages over the period was pound11
      million. The mean level of damages was pound37,100. Cataract made up the largest
      share of claims (31%), paediatric ophthalmology had the highest mean damages (
      pound170,000), and claims related to glaucoma were most likely to result in
      payment of damages (64%). CONCLUSION: Clinical negligence claims in ophthalmology
      in England are infrequent, but most ophthalmologists will face at least one in
      their career. Ophthalmic subspecialties show marked differences with regard to
      their litigation profiles. From a medical protection perspective, these results
      suggest that indemnity premiums should be tailored according to the subspecialty
      areas an ophthalmologist is involved in.

PMID- 18096076
TI  - Differential regulation of NAB corepressor genes in Schwann cells.
AB  - BACKGROUND: Myelination of peripheral nerves by Schwann cells requires not only
      the Egr2/Krox-20 transactivator, but also the NGFI-A/Egr-binding (NAB)
      corepressors, which modulate activity of Egr2. Previous work has shown that axon
      dependent expression of Egr2 is mediated by neuregulin stimulation, and NAB
      corepressors are co-regulated with Egr2 expression in peripheral nerve
      development. NAB corepressors have also been implicated in macrophage
      development, cardiac hypertrophy, prostate carcinogenesis, and feedback
      regulation involved in hindbrain development. RESULTS: To test the mechanism of
      NAB regulation in Schwann cells, transfection assays revealed that both Nab1 and
      Nab2 promoters are activated by Egr2 expression. Furthermore, direct binding of
      Egr2 at these promoters was demonstrated in vivo by chromatin immunoprecipitation
      analysis of myelinating sciatic nerve, and binding of Egr2 to the Nab2 promoter
      was stimulated by neuregulin in primary Schwann cells. Although Egr2 expression
      activates the Nab2 promoter more highly than Nab1, we surprisingly found that
      only Nab1 - but not Nab2 - expression levels were reduced in sciatic nerve from
      Egr2 null mice. Analysis of the Nab2 promoter showed that it is also activated by
      ETS proteins (Ets2 and Etv1/ER81) and is bound by Ets2 in vivo. CONCLUSION:
      Overall, these results indicate that induction of Nab2 expression in Schwann
      cells involves not only Egr2, but also ETS proteins that are activated by
      neuregulin stimulation. Although Nab1 and Nab2 play partially redundant roles,
      regulation of Nab2 expression by ETS factors explains several observations
      regarding regulation of NAB genes. Finally, these data suggest that NAB proteins
      are not only feedback inhibitors of Egr2, but rather that co-induction of Egr2
      and NAB genes is involved in forming an Egr2/NAB complex that is crucial for
      regulation of gene expression.

PMID- 18096078
TI  - Cyclooxygenase inhibition lowers prostaglandin E2 release from articular
      cartilage and reduces apoptosis but not proteoglycan degradation following an
      impact load in vitro.
AB  - This study investigated the release of prostaglandin E2 (PGE2) from cartilage
      following an impact load in vitro and the possible chondroprotective effect of
      cyclooxygenase-2 (COX-2) inhibition using non-steroidal anti-inflammatory drugs
      (NSAIDs). Explants of human articular cartilage were subjected to a single impact
      load in a drop tower, and then cultured for 6 days in the presence of either a
      selective COX-2 inhibitor (celecoxib; 0.01, 0.1, 1.0 and 10 microM) or a non
      selective COX inhibitor (indomethacin; 0.1 and 10 microM). The concentrations of
      PGE2 and glycosaminoglycans (GAGs), a measure of cartilage breakdown, were
      measured in the explant culture medium at 3 and 6 days post-impact. Apoptotic
      cell death was measured in frozen explant sections by the terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method.
      PGE2 levels were increased by more than 20-fold in the medium of explants at both
      3 (p = 0.012) and 6 days (p = 0.004) following impact, compared with unloaded
      controls. In the presence of celecoxib and indomethacin, the PGE2 levels were
      reduced in a dose-related manner. These inhibitors, however, had no effect in
      reducing the impact-induced release of GAGs from the cartilage matrix. Addition
      of celecoxib and indomethacin significantly reduced the number of trauma-induced
      apoptotic chondrocytes in cartilage explant sections. In this study, a marked
      increase in PGE2 was measured in the medium following an impact load on articular
      cartilage, which was abolished by the selective COX-2 inhibitor, celecoxib, and
      non-selective indomethacin. These inhibitors reduced chondrocyte apoptosis but no
      change was observed in the release of GAGs from the explants, suggesting that the
      COX/PGE2 pathway is not directly responsible for cartilage breakdown following
      traumatic injury. Our in vitro study demonstrates that it is unlikely that COX-2
      inhibition alone would slow down or prevent the development of secondary
      osteoarthritis.

PMID- 18096079
TI  - Using machine learning algorithms to guide rehabilitation planning for home care
      clients.
AB  - BACKGROUND: Targeting older clients for rehabilitation is a clinical challenge
      and a research priority. We investigate the potential of machine learning
      algorithms - Support Vector Machine (SVM) and K-Nearest Neighbors (KNN) - to
      guide rehabilitation planning for home care clients. METHODS: This study is a
      secondary analysis of data on 24,724 longer-term clients from eight home care
      programs in Ontario. Data were collected with the RAI-HC assessment system, in
      which the Activities of Daily Living Clinical Assessment Protocol (ADLCAP) is
      used to identify clients with rehabilitation potential. For study purposes, a
      client is defined as having rehabilitation potential if there was: i) improvement
      in ADL functioning, or ii) discharge home. SVM and KNN results are compared with
      those obtained using the ADLCAP. For comparison, the machine learning algorithms
      use the same functional and health status indicators as the ADLCAP. RESULTS: The
      KNN and SVM algorithms achieved similar substantially improved performance over
      the ADLCAP, although false positive and false negative rates were still fairly
      high (FP > .18, FN > .34 versus FP > .29, FN. > .58 for ADLCAP). Results are used
      to suggest potential revisions to the ADLCAP. CONCLUSION: Machine learning
      algorithms achieved superior predictions than the current protocol. Machine
      learning results are less readily interpretable, but can also be used to guide
      development of improved clinical protocols.

PMID- 18096080
TI  - TaMSH7: a cereal mismatch repair gene that affects fertility in transgenic barley
      (Hordeum vulgare L.).
AB  - BACKGROUND: Chromosome pairing, recombination and DNA repair are essential
      processes during meiosis in sexually reproducing organisms. Investigating the
      bread wheat (Triticum aestivum L.) Ph2 (Pairing homoeologous) locus has
      identified numerous candidate genes that may have a role in controlling such
      processes, including TaMSH7, a plant specific member of the DNA mismatch repair
      family. RESULTS: Sequencing of the three MSH7 genes, located on the short arms of
      wheat chromosomes 3A, 3B and 3D, has revealed no significant sequence divergence
      at the amino acid level suggesting conservation of function across the
      homoeogroups. Functional analysis of MSH7 through the use of RNAi loss-of
      function transgenics was undertaken in diploid barley (Hordeum vulgare L.).
      Quantitative real-time PCR revealed several T0 lines with reduced MSH7
      expression. Positive segregants from two T1 lines studied in detail showed
      reduced MSH7 expression when compared to transformed controls and null
      segregants. Expression of MSH6, another member of the mismatch repair family
      which is most closely related to the MSH7 gene, was not significantly reduced in
      these lines. In both T1 lines, reduced seed set in positive segregants was
      observed. CONCLUSION: Results presented here indicate, for the first time, a
      distinct functional role for MSH7 in vivo and show that expression of this gene
      is necessary for wild-type levels of fertility. These observations suggest that
      MSH7 has an important function during meiosis and as such remains a candidate for
      Ph2.

PMID- 18096081
TI  - H-Profile plots for the discovery and exploration of patterns in gene expression
      data with an application to time course data.
AB  - BACKGROUND: An ever increasing number of techniques are being used to find genes
      with similar profiles from microarray studies. Visualization of gene expression
      profiles can aid this process, potentially contributing to the identification of
      co-regulated genes and gene function as well as network development. RESULTS: We
      introduce the h-Profile plot to display gene expression profiles. Thumbnail
      versions of plots of gene expression profiles are plotted at coordinates such
      that profiles of similar shape are located in the same sector, with decreasing
      variance towards the origin. Negatively correlated profiles can easily be
      identified. A new method for selecting genes with fixed periodicity, but
      different phase and amplitude is described and used to demonstrate the use of the
      plots on cell cycle data. CONCLUSION: Visualization tools for gene expression
      data are important and h-profile plots provide a timely contribution to the
      field. They allow the simultaneous visualization of many gene expression profiles
      and can be used for the identification of genes with similar or reversed
      profiles, the foundation step in many analyses.

PMID- 18096082
TI  - Occupational correlates of smoking among urban transit operators: a prospective
      study.
AB  - BACKGROUND: Workers in blue-collar and service occupations smoke at higher rates
      than workers in white-collar and professional occupations. Occupational stress
      may explain some of the occupational class differences in smoking and quitting
      behavior. The purpose of this study is to investigate the contribution of
      occupational factors to smoking behavior over a ten year period among a
      multiethnic cohort of urban transit operators, while accounting for demographic
      factors and alcohol. METHODS: The sample consists of 654 San Francisco Municipal
      Railway (MUNI) transit operators who participated in two occupational health
      studies and biennial medical examinations during 1983-85 and 1993-95. Workers who
      had initiated, increased, or maintained their smoking over the ten year period
      were compared to workers who remained non-smokers. Occupational factors included
      self-rated frequency of job problems (e.g., difficulties with equipment,
      passengers, traffic), job burnout (i.e., the emotional exhaustion subscale of the
      Maslach Burnout Inventory), time needed to unwind after work, and years employed
      as a transit operator. A series of logistic regression models were developed to
      estimate the contribution of occupational factors to smoking behavior over time.
      RESULTS: Approximately 35% of the workers increased, initiated, or maintained
      their smoking over the ten-year period. Frequency of job problems was
      significantly associated with likelihood of smoking increase, initiation, or
      maintenance (OR = 1.30; 95% CI 1.09, 1.55). Black operators were significantly
      more likely to have smoked over the ten-year period compared to operators in
      other racial/ethnic groups. CONCLUSION: Understanding the role of work-related
      stress vis-a-vis smoking behavior is of critical importance for crafting
      workplace smoking prevention and cessation interventions that are applicable to
      blue-collar work settings, and for developing policies that mitigate occupational
      stress.

PMID- 18096083
TI  - Factors influencing cerebrospinal fluid and plasma HIV-1 RNA detection rate in
      patients with and without opportunistic neurological disease during the HAART
      era.
AB  - BACKGROUND: In the central nervous system, HIV replication can occur relatively
      independent of systemic infection, and intrathecal replication of HIV-1 has been
      observed in patients with HIV-related and opportunistic neurological diseases.
      The clinical usefulness of HIV-1 RNA detection in the cerebrospinal fluid (CSF)
      of patients with opportunistic neurological diseases, or the effect of
      opportunistic diseases on CSF HIV levels in patients under HAART has not been
      well defined. We quantified CSF and plasma viral load in HIV-infected patients
      with and without different active opportunistic neurological diseases, determined
      the characteristics that led to a higher detection rate of HIV RNA in CSF, and
      compared these two compartments. METHODS: A prospective study was conducted on 90
      HIV-infected patients submitted to lumbar puncture as part of a work-up for
      suspected neurological disease. Seventy-one patients had active neurological
      diseases while the remaining 19 did not. RESULTS: HIV-1 RNA was quantified in 90
      CSF and 70 plasma samples. The HIV-1 RNA detection rate in CSF was higher in
      patients with neurological diseases, in those with a CD4 count lower than 200
      cells/mm3, and in those not receiving antiretroviral therapy, as well as in
      patients with detectable plasma HIV-1 RNA. Median viral load was lower in CSF
      than in plasma in the total population, in patients without neurological
      diseases, and in patients with toxoplasmic encephalitis, while no significant
      difference between the two compartments was observed for patients with
      cryptococcal meningitis and HIV-associated dementia. CSF viral load was lower in
      patients with cryptococcal meningitis and neurotoxoplasmosis under HAART than in
      those not receiving HAART. CONCLUSION: Detection of HIV-1 RNA in CSF was more
      frequent in patients with neurological disease, a CD4 count lower than 200
      cells/mm3 and detectable plasma HIV-1. Median HIV-1 RNA levels were generally
      lower in CSF than in plasma but some patients showed higher CSF levels, and no
      difference between these two compartments was observed in patients with
      cryptococcal meningitis and HIV-associated dementia, suggesting the presence of
      intrathecal viral replication in these patients. HAART played a role in the
      control of CSF HIV levels even in patients with cryptococcal meningitis and
      neurotoxoplasmosis in whom viral replication is potentially higher.

PMID- 18096084
TI  - Fra-1 governs cell migration via modulation of CD44 expression in human
      mesotheliomas.
AB  - Silencing of Fra-1, a component of the dimeric transcription factor, activator
      protein-1 (AP-1), inhibits mRNA expression of c-met and cd44 in rat mesothelioma
      cells and is causally linked to maintenance of the transformed phenotype.
      However, the mechanisms of Fra-1 regulation and Fra-1 regulated gene expression
      in human malignant mesothelioma (MM) are unclear. We first show in a panel of
      human MM cells that Fra-1 mRNA expression in MM is complex and regulated by
      extracellular signal-regulated kinase (ERK1, ERK2), Src, and phosphatidyl
      inositol-3-kinase (PI3K) pathways in a tumor-specific fashion. Cell lines with
      PI3K-dependent Fra-1 expression were SV40 positive and expressed the lowest basal
      Fra-1 levels. Levels of Fra-1 expression correlated with amounts of CD44
      expression that were greater in simian virus 40 negative (SV40-) MM cells. Using
      dominant negative (dn), short hairpin (sh) and small interference (si) RNA
      constructs, we next demonstrate that expression of CD44, the principal hyaluronic
      receptor in MMs, correlates with Fra-expression in both simian virus 40 positive
      (SV40+) and SV40- MMs. Moreover, both Fra-1 and CD44 expression are linked to
      cell migration in SV40- MM cells. Lastly, in contrast to normal lung tissue,
      tissue microarrays revealed that Fra-1 was expressed in 33 of 34 human MMs, and
      that all CD44+ tumors were SV40-. These results suggest that Fra-1 is associated
      with cell migration in human MMs and that Fra-1 modulation of CD44 may govern
      migration of selected MMs.

PMID- 18096086
TI  - The quest for the Holy Grail: a disease-modifying osteoarthritis drug.
AB  - The unfortunate story of the matrix metalloproteinase inhibitor PG116800, which
      had no effect on the osteoarthritic process but had unexpected side effects,
      highlights the following. First, reality does not always match the theory.
      Second, cell biology data must be interpreted within the context of a specific
      environment. Third, the specificity of an enzyme inhibitor is always relative.
      Finally, a critical evaluation of the benefit/risk ratio of a drug must be
      carefully conducted and checked before and after launch. Well designed post
      marketing surveillance is mandatory.

PMID- 18096085
TI  - The effects of NaCl concentration and pH on the stability of hyperthermophilic
      protein Ssh10b.
AB  - BACKGROUND: Hyperthermophiles constitute a group of microorganisms with an
      optimum growth temperature of between 80 degrees C and 100 degrees C. Although
      the molecular underpinnings of protein thermostabilization have been the focus of
      many theoretical and experimental efforts, the properties leading to the higher
      denaturation temperature of hyperthermophilic proteins are still controversial.
      Among the large number of factors identified as responsible for the
      thermostability of hyperthermophilic proteins, the electrostatic interactions are
      thought to be a universally important factor. RESULTS: In this study, we report
      the effects of pH and salt concentration on the urea-induced denaturation of the
      protein Ssh10b from a hyperthermophile in low ionic strength buffer. In the
      absence of NaCl, the unfolding DeltaG of the protein increased from about 33
      kJ/mol at pH 3 to about 78 kJ/mol at pH 10. At all values of pH, the DeltaG
      increased with increasing NaCl concentration, indicating that salt stabilizes the
      protein significantly. CONCLUSION: These findings suggests that the increased
      number of charged residues and ion pairs in the protein Ssh10b from
      hyperthermophiles does not contribute to the stabilization of the folded protein,
      but may play a role in determining the denatured state ensemble and also in
      increasing the denaturation temperature.

PMID- 18096087
TI  - The promise and limitations of genome-wide association studies to elucidate the
      causes of breast cancer.
AB  - With the characterization of the human genome, as well as advances in technology
      to determine genetic variability across the genomes of populations, there has
      been focused effort on the identification of cancer susceptibility alleles
      through the use of genome-wide association studies. These efforts have recently
      resulted in identification of a susceptibility locus for breast cancer by several
      groups, although the increases in risk are modest. While genome-wide association
      studies will probably lead to discoveries of potentially important previously
      unstudied pathways in cancer etiology, the role of the environment, particularly
      gene-environment interactions, in breast cancer etiology should not be
      overlooked.

PMID- 18096089
TI  - Gene prediction: compare and CONTRAST.
AB  - CONTRAST, a new gene-prediction algorithm that uses sophisticated machine
      learning techniques, has pushed de novo prediction accuracy to new heights, and
      has significantly closed the gap between de novo and evidence-based methods for
      human genome annotation.

PMID- 18096088
TI  - Bench-to-bedside review: mechanisms and management of hyperthermia due to
      toxicity.
AB  - Body temperature can be severely disturbed by drugs capable of altering the
      balance between heat production and dissipation. If not treated aggressively,
      these events may become rapidly fatal. Several toxins can induce such non
      infection-based temperature disturbances through different underlying mechanisms.
      The drugs involved in the eruption of these syndromes include sympathomimetics
      and monoamine oxidase inhibitors, antidopaminergic agents, anticholinergic
      compounds, serotonergic agents, medicaments with the capability of uncoupling
      oxidative phosphorylation, inhalation anesthetics, and unspecific agents causing
      drug fever. Besides centrally disturbed regulation disorders, hyperthermia often
      results as a consequence of intense skeletal muscle hypermetabolic reaction. This
      leads mostly to rapidly evolving muscle rigidity, extensive rhabdomyolysis,
      electrolyte disorders, and renal failure and may be fatal. The goal of treatment
      is to reduce body core temperature with both symptomatic supportive care,
      including active cooling, and specific treatment options.

PMID- 18096090
TI  - Vitamin D status in Sri Lankans living in Sri Lanka and Norway.
AB  - Vitamin D deficiency is common in non-Western immigrant groups living in Western
      countries. A comparison of vitamin D status in individuals who have emigrated and
      individuals who remain in their country of origin is needed in order to provide
      information about the effect of moving to northern latitudes. A total of 196
      participants aged 30-60 years in a cross-sectional population-based study in
      Kandy, Sri Lanka (latitude 7 degrees north) and 242 Sri Lankans aged 31-60 years
      participating in a cross-sectional population-based study in Oslo, Norway
      (latitude 60 degrees north) were included in the analysis. All serum samples were
      analysed for serum 25-hydroxyvitamin D (s-25(OH)D) in the same laboratory. Sri
      Lankans living in Norway had substantially lower s-25(OH)D (mean 31.5 nmol/l)
      compared with those living in Sri Lanka (mean 54.2 nmol/l), and the prevalence of
      s-25(OH)D < 25 nmol/l was 9.3 times higher (95 % CI 4.4, 19.6) in Norway compared
      with Sri Lanka. In Sri Lanka there was a clear seasonal variation with the lowest
      s-25(OH)D levels in August-September and the highest levels in November-December.
      We conclude that vitamin D status among Sri Lankans living in Kandy, Sri Lanka
      was considerably higher than that among Sri Lankans living in Oslo, Norway. The
      low vitamin D status commonly observed in non-Western immigrant groups living at
      northern latitudes should not be regarded as normal levels for these groups.
      However, also in Sri Lanka we found a profound seasonal variation with the lowest
      levels in August and September after the Monsoon.

PMID- 18096091
TI  - Lupin protein influences the expression of hepatic genes involved in fatty acid
      synthesis and triacylglycerol hydrolysis of adult rats.
AB  - To assess the effect of lupin protein on concentrations of lipids in plasma
      lipoproteins and liver and hepatic mRNA concentrations of genes involved in lipid
      metabolism, adult rats were fed egg albumin-based diets containing either lupin
      protein from Lupinus albus or casein (50 g/kg) supplemented
      (hypercholesterolaemic) or not (normolipaemic) with a cholesterol-cholate mixture
      for 20 d. Lupin protein compared with casein lowered the concentrations of TAG in
      liver (P < 0.01) and circulating VLDL + chylomicrons (P < 0.05) of
      hypercholesterolaemic rats, but not of normolipaemic rats. Hepatic mRNA
      concentrations of genes involved in fatty acid synthesis such as sterol
      regulatory element-binding protein-1c, glucose-6-phosphate dehydrogenase, fatty
      acid synthase, stearoyl-CoA desaturase-1 and acyl-CoA:glycerol-3-phosphate
      acyltransferase were lower and mRNA concentrations of lipoprotein lipase, hepatic
      lipase and apoA5 involved in TAG hydrolysis were higher in rats fed lupin protein
      than in rats fed casein. These effects were stronger in hypercholesterolaemic
      rats than in normolipaemic rats. Hypercholesterolaemic rats fed the lupin protein
      had higher liver cholesterol concentrations (P < 0.01) and lower levels of LDL
      cholesterol (P < 0.05) than rats fed casein. No effect of lupin protein was
      observed on cholesterol concentration in VLDL + chylomicrons and HDL and hepatic
      mRNA concentrations of genes involved in cholesterol and bile acid metabolism. In
      conclusion, the present study shows that lupin protein has
      hypotriacylglycerolaemic action possibly via down regulation of fatty acid
      synthesis genes and up regulation of genes involved in TAG hydrolysis.
      Alterations in cholesterol metabolism could not be explained on the basis of mRNA
      data.

PMID- 18096092
TI  - Relationship between energy from added sugars and frequency of added sugars
      intake in Irish children, teenagers and adults.
AB  - A WHO report on diet, nutrition and the prevention of chronic diseases
      recommended that frequency of consumption of foods and/or drinks containing free
      sugars should be limited to a maximum of four times per d. In addition, they
      recommended a reduction in the intake of free sugars to a maximum of no more than
      10 % of energy intake. These recommendations were developed with the aim of
      reducing the prevalence of dental caries. The aim of the present study was to
      establish if there is a quantitative relationship between energy from added
      sugars and frequency of added sugars intakes in Irish children, teenagers and
      adults. In addition, the intake of added and total sugars and main contributors
      to added sugar intakes were examined. Data for the present analysis were based on
      the North/South Ireland Food Consumption Survey (n 1379; aged 18-64 years), the
      National Children's Food Survey (n 594; aged 5-12 years) and the National Teen
      Food Survey (n 441; aged 13-17 years) which used 7 d food diaries to collect food
      and beverage intake data in representative samples of Irish adults, children and
      teenagers respectively. Results showed that in adults, frequency of intake of
      added sugar intake of four times per d corresponded to a mean added sugar intake
      of 9 %, which was similar to the WHO recommendation. In children and teenagers, a
      frequency of intake of four times per d corresponded to a mean added sugar intake
      of 14.6 and 12.4 % respectively and was therefore not in agreement with the WHO
      recommendation.

PMID- 18096093
TI  - Assessing changes in composition of intestinal microbiota in neonatal BALB/c mice
      through cluster analysis of molecular markers.
AB  - The present study introduced a molecular biological approach to demonstrate
      changes in the composition of intestinal microbiota in neonatal mice. Female
      BALB/c mice were fed either a control diet or a diet supplemented with fructo
      oligosaccharide (FOS) at 50 g/kg diet, and then mated to male mice. A cultivation
      independent approach, denaturing gradient gel electrophoresis (DGGE) of the PCR
      amplified 16S rRNA gene, was performed to characterise changes in intestinal
      microbial populations in pups at 0, 7, 14 and 21 d old and their dams.
      Comparisons of DGGE profiles were performed using the Dice similarity coefficient
      and the unweighted pair group method with arithmetic mean (UPGMA) cluster
      analysis based on numbers, positions and intensities of bands. DGGE profiles
      differed between dams fed control and FOS-supplemented diets. Although profiles
      in pups on the day of birth showed a high similarity with dams, profiles in 7-d
      old pups differed from dams and showed high similarity to littermates. In 14- and
      21-d-old pups, profiles again showed high similarity with dams. DGGE profiles in
      pups were divided into two large clusters of control and FOS-supplemented diet
      groups in the range of 0- to 21-d-old, suggesting modulation of intestinal
      microbiota in infants by manipulation of microbiota in dams. The present study
      shows a useful technique for demonstrating changes in intestinal microbiota and
      provides a mouse model for modulation of intestinal microbiota in neonatal life.

PMID- 18096095
TI  - Relationship between women's occupational work and bone health: a study from
      India.
AB  - Physical activity is known to influence the bone mass of an individual. Few
      studies have examined the effect of occupational activities on bone health. The
      present study investigated the relationship between occupational activities and
      the bone parameters measured by dual-energy X-ray absorptiometry in 158 women
      from a low-income group in India. Women involved in three occupations with
      different bone-loading patterns (beedi (cigarette) makers, sweepers and
      construction workers) were included in the study. Anthropometric parameters,
      parity and percentage of menopausal women did not differ significantly between
      the three groups and dietary intake of Ca was low in all the groups. Bone mineral
      density (BMD) values of the overall group at all the sites were much lower than
      those reported from developed countries, possibly due to different body sizes in
      these regions. Femoral neck and hip BMD were not different in the three groups in
      spite of marked differences in activity patterns. However, bone area in the
      femoral neck was higher in the beedi makers compared with sweepers probably due
      to the squatting position adopted by beedi makers. Lumbar spine BMD was
      significantly lower among the sweepers when compared with the beedi makers and
      the groups performing walking and weight-bearing activities (sweepers and
      construction workers) had a higher prevalence of osteoporosis in the lumbar
      spine. However, weight-bearing effects of the upper body due to a squatting
      position were associated with better lumbar spine BMD in the beedi makers. The
      present study thus indicates that undernutrition might affect the relationship
      between occupational activities and bone parameters.

PMID- 18096094
TI  - Concentrations of resveratrol and derivatives in foods and estimation of dietary
      intake in a Spanish population: European Prospective Investigation into Cancer
      and Nutrition (EPIC)-Spain cohort.
AB  - Resveratrol has been shown to have beneficial effects on diseases related to
      oxidant and/or inflammatory processes and extends the lifespan of simple
      organisms including rodents. The objective of the present study was to estimate
      the dietary intake of resveratrol and piceid (R&P) present in foods, and to
      identify the principal dietary sources of these compounds in the Spanish adult
      population. For this purpose, a food composition database (FCDB) of R&P in
      Spanish foods was compiled. The study included 40,685 subjects aged 35-64 years
      from northern and southern regions of Spain who were included in the European
      Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual
      food intake was assessed by personal interviews using a computerised version of a
      validated diet history method. An FCDB with 160 items was compiled. The estimated
      median and mean of R&P intake were 100 and 933 microg/d respectively.
      Approximately, 32% of the population did not consume R&P. The most abundant of
      the four stilbenes studied was trans-piceid (53.6%), followed by trans
      resveratrol (20.9%), cis-piceid (19.3%) and cis-resveratrol (6.2%). The most
      important source of R&P was wines (98.4%) and grape and grape juices (1.6%),
      whereas peanuts, pistachios and berries contributed to less than 0.01%. For this
      reason the pattern of intake of R&P was similar to the wine pattern. This is the
      first time that R&P intake has been estimated in a Mediterranean country.

PMID- 18096096
TI  - Electron holography with a Cs-corrected transmission electron microscope.
AB  - Cs correctors have revolutionized transmission electron microscopy (TEM) in that
      they substantially improve point resolution and information limit. The object
      information is found sharply localized within 0.1 nm, and the intensity image can
      therefore be interpreted reliably on an atomic scale. However, for a conventional
      intensity image, the object exit wave can still not be detected completely in
      that the phase, and hence indispensable object information is missing. Therefore,
      for example, atomic electric-field distributions or magnetic domain structures
      cannot be accessed. Off-axis electron holography offers unique possibilities to
      recover completely the aberration-corrected object wave with uncorrected
      microscopes and hence we would not need a Cs-corrected microscope for improved
      lateral resolution. However, the performance of holography is affected by
      aberrations of the recording TEM in that the signal/noise properties ("phase
      detection limit") of the reconstructed wave are degraded. Therefore, we have
      realized off-axis electron holography with a Cs-corrected TEM. The phase
      detection limit improves by a factor of four. A further advantage is the
      possibility of fine-tuning the residual aberrations by a posteriori correction.
      Therefore, a combination of both methods, that is, Cs correction and off-axis
      electron holography, opens new perspectives for complete TEM analysis on an
      atomic scale.

PMID- 18096097
TI  - Contrast transfer and resolution limits for sub-angstrom high-resolution
      transmission electron microscopy.
AB  - The optimum imaging of an object structure at the sub-angstrom length scale
      requires precise adjustment of the lens aberrations of a high-resolution
      instrument up to the fifth order. A least-squares optimization of defocus
      aberration C1, third-order spherical aberration C3, and fifth-order spherical
      aberration C5 yields two sets of aberration coefficients for strong phase
      contrast up to the information limit: one for variable C1 and C3, at fixed C5,
      another for variable C1, C3, and C5. An additional correction to the defocus
      aberration, dependent on object thickness, is described, which becomes important
      for the use of image simulation programs in predicting optimum high-resolution
      contrast from thin objects at the sub-angstrom scale. For instruments with a sub
      angstrom information limit the ultimate structure resolution, the power to
      resolve adjacent atom columns in a crystalline object, depends on both the
      instrumental pointspread and an object pointspread due to finite width of the
      atomic column potentials. A simulation study on a simple double-column model
      yields a range for structure resolutions, dependent on the atomic scattering
      power, from 0.070 nm down to 0.059 nm, for a hypothetical 300-kV instrument with
      an information limit of 0.050 nm.

PMID- 18096098
TI  - Imaging modes for scanning confocal electron microscopy in a double aberration
      corrected transmission electron microscope.
AB  - Aberration correction leads to reduced focal depth of field in the electron
      microscope. This reduced depth of field can be exploited to probe specific depths
      within a sample, a process known as optical sectioning. An electron microscope
      fitted with aberration correctors for both the pre- and postspecimen optics can
      be used in a confocal mode that provides improved depth resolution and
      selectivity over optical sectioning in the scanning transmission electron
      microscope (STEM). In this article we survey the coherent and incoherent imaging
      modes that are likely to be used in scanning confocal electron microscopy (SCEM)
      and provide simple expressions to describe the images that result. Calculations
      compare the depth response of SCEM to optical sectioning in the STEM. The depth
      resolution in a crystalline matrix is also explored by performing a Bloch wave
      calculation for the SCEM geometry in which the pre- and postspecimen optics are
      defocused away from their confocal conditions.

PMID- 18096099
TI  - Aberration-corrected STEM imaging of Ag on gamma-Al2O3.
AB  - Ag on gamma-alumina is a promising catalyst for hydrocarbon selective catalytic
      reduction in lean-burn gasoline and diesel engines for transportation
      applications. Although much is known about the mechanism of NOx reduction and the
      various intermediates, little agreement exists on the nature of the active silver
      species. In the present work, aberration-corrected STEM has provided new
      information about the nature of Ag on alumina both as impregnated and following
      treatments at various temperatures with exposure to simulated exhaust gas. Ex
      situ techniques have provided new insights into the evolution of Ag on alumina
      following exposure to temperature and simulated exhaust gas.

PMID- 18096100
TI  - Motion of gold atoms on carbon in the aberration-corrected STEM.
AB  - The movement of heavy atoms on a thin carbon substrate is readily observed using
      a sub-Angstrom electron probe. The observed movement is consistent with an
      electron beam activation mechanism whereby atoms are occasionally detached from
      bonding sites, allowing rapid diffusion to new sites that may be quite far from
      the original. The bonding sites are most often observed to lie at defects, steps,
      and other asperities in the substrate. Formation of three-dimensional clusters
      can occur during diffusion of several isolated atoms. Coalescence and dissolution
      of larger clusters and islands both occur under varying observation conditions,
      but island coalescence appears most probable for islands that are greater than 2
      nm in size.

PMID- 18096101
TI  - Modeling atomic-resolution scanning transmission electron microscopy images.
AB  - A real-space description of inelastic scattering in scanning transmission
      electron microscopy is derived with particular attention given to the
      implementation of the projected potential approximation. A hierarchy of
      approximations to expressions for inelastic images is presented. Emphasis is
      placed on the conditions that must hold in each case. The expressions that
      justify the most direct, visual interpretation of experimental data are also the
      most approximate. Therefore, caution must be exercised in selecting experimental
      parameters that validate the approximations needed for the analysis technique
      used. To make the most direct, visual interpretation of electron-energy-loss
      spectroscopic images from core-shell excitations requires detector improvements
      commensurate with those that aberration correction provides for the probe-forming
      lens. Such conditions can be relaxed when detailed simulations are performed as
      part of the analysis of experimental data.

PMID- 18096102
TI  - Changes in epidemiology of leptospirosis in 2003--2004, a two El Nino Southern
      Oscillation period, Guadeloupe archipelago, French West Indies.
AB  - Our study aimed at analysing the changes in epidemiological features of
      leptospirosis cases from the hospital of Pointe a Pitre in Guadeloupe in 2003-
      2004 compared to reliable data in 1994--2001. Leptospirosis incidence increased
      fourfold during 2002--2004, a period with two El Nino events. Whereas the main
      risk factors were unchanged (male gender, occupational exposure, contact with
      cattle or pigs) a major role of rodent exposure emerged (52%, P=0.02,
      multivariate analysis). Interestingly, mean age of cases shifted to the older
      population (51.7 years vs. 43 years, P<0.05). Moreover, the Ballum serogroup rose
      dramatically (36% of incidence) competing with the Icterohaemorragiae serogroup
      (62%). However, severe forms were less recorded. Our data suggest that the
      changes in leptospirosis features could be related to exceptional meteorological
      events and their consequences on rodent populations. We propose the monitoring of
      rodent population and climatic data as a tool of management of leptospirosis in
      Guadeloupe.

PMID- 18096103
TI  - Hyaluronic acid ester in myringoplasty.
AB  - OBJECTIVES: To investigate the use of a new technique to close persistent
      tympanic membrane perforations under general anaesthesia, in patients in whom
      this has previously been considered impractical. DESIGN: Twenty patients aged 50
      years and over were recruited. All had a persistent, symptomatic tympanic
      membrane perforation in at least one ear. Pre-operatively, an audiogram was
      performed and the tympanic membrane was assessed in order to establish the site
      and size of the perforation. Under general anaesthesia, the edges of the
      perforation were freshened and a sheet of Epifilm, trimmed to a size roughly 2 mm
      larger in diameter than the perforation, was tucked through the perforation. The
      ear was dressed appropriately. Patients were seen two weeks post-operatively in
      the out-patients department and reassessed. SETTING: The study was based at Poole
      General Hospital, a District General Hospital. PARTICIPANTS: Twenty patients were
      recruited from the out-patients clinics of Poole Hospital ENT department. MAIN
      OUTCOME MEASURES: (1) closure of the perforation, as a percentage of the original
      size; (2) improvement of hearing, as an average across all frequencies, expressed
      in dB hearing level; and (3) presence or absence of discharge. RESULTS: Five
      patients were operated upon and assessed six weeks post-operatively. The Epifilm
      had dissolved but the perforations remained the same size in all five patients.
      There were no other adverse effects. Pure tone audiometry at this stage was
      redundant. The study was subsequently aborted. CONCLUSIONS: The authors conclude
      that repair of tympanic membrane perforations with hyaluronic acid ester films is
      not to be recommended.

PMID- 18096104
TI  - Product variety in Australian snacks and drinks: how can the consumer make a
      healthy choice?
AB  - OBJECTIVE: To estimate the proportion of snack food and beverage choices
      available to an Australian consumer. DESIGN: A survey of product Nutrition
      Information Panels (NIP) and product labels on snack foods and beverages offered
      for sale. Data on nutrient content were compared with criteria from different
      nutrient profile systems to estimate the proportion of items conforming to a
      choice. SETTING: A large supermarket in metropolitan Melbourne, Australia.
      RESULTS: A consumer could choose from 1,070 different snack foods and 863
      different drinks. Flavour variety was more common in snacks (maximum thirteen per
      product) while variation in container size was more common for drinks (up to ten
      per product). Recommended serving size for snacks varied greatly (1822 % of snack
      foods presented for sale could be deemed by multiple criteria. Similarly, only 14
      healthy healthier' snack foods and beverages, e.g. by reformulation of many
      products by the food industry and their presentation in smaller, standardised
      portion-size packaging.

PMID- 18096105
TI  - Maize meal fortification is associated with improved vitamin A and iron status in
      adolescents and reduced childhood anaemia in a food aid-dependent refugee
      population.
AB  - OBJECTIVE: To assess changes in the Fe and vitamin A status of the population of
      Nangweshi refugee camp associated with the introduction of maize meal
      fortification. DESIGN: Pre- and post-intervention study using a longitudinal
      cohort. SETTING: Nangweshi refugee camp, Zambia. SUBJECTS: Two hundred and twelve
      adolescents (10-19 years), 157 children (6-59 months) and 118 women (20-49 years)
      were selected at random by household survey in July 2003 and followed up after 12
      months. RESULTS: Maize grain was milled and fortified in two custom-designed
      mills installed at a central location in the camp and a daily ration of 400 g per
      person was distributed twice monthly to households as part of the routine food
      aid ration. During the intervention period mean Hb increased in children (0.87
      g/dl; P < 0.001) and adolescents (0.24 g/dl; P = 0.043) but did not increase in
      women. Anaemia decreased in children by 23.4% (P < 0.001) but there was no
      significant change in adolescents or women. Serum transferrin receptor (log10
      transformed) decreased by -0.082 microg/ml (P = 0.036) indicating an improvement
      in the Fe status of adolescents but there was no significant decrease in the
      prevalence of deficiency (-8.5%; P = 0.079). In adolescents, serum retinol
      increased by 0.16 micromol/l (P < 0.001) and vitamin A deficiency decreased by
      26.1% (P < 0.001). CONCLUSIONS: The introduction of fortified maize meal led to a
      decrease in anaemia in children and a decrease in vitamin A deficiency in
      adolescents. Centralised, camp-level milling and fortification of maize meal is a
      feasible and pertinent intervention in food aid operations.

PMID- 18096106
TI  - Antidepressant medications and other treatments of depressive disorders: a CINP
      Task Force report based on a review of evidence.

PMID- 18096108
TI  - Mechanisms of implementation intention effects: the role of goal intentions, self
      efficacy, and accessibility of plan components.
AB  - Although considerable evidence suggests that forming an implementation intention
      increases rates of goal attainment, less research has examined the mechanisms
      that underlie these effects. The present research investigated the role of
      deliberative processes and accessibility of plan components as explanation for
      the relationship between implementation intentions and goal achievement. Study 1
      used meta-analysis to quantify the effects of implementation intentions on goal
      intentions and self-efficacy. The results of 66 tests suggested that forming
      implementation intentions had negligible effects on both variables. Study 2
      focused on the accessibility of plan components and found that the effect of
      implementation intentions on goal achievement was mediated simultaneously by the
      accessibility of specified situational cues and by the strength of the
      association forged between these cues and the intended response. These findings
      suggest that implementation intention effects are not explained by increased
      deliberation, but rather accrue from heightened accessibility of specified
      opportunities and strong opportunity-response links.

PMID- 18096107
TI  - Effects of dendroaspis natriuretic peptide on calcium-activated potassium current
      and its mechanism.
AB  - In this study, we sought to investigate the effect of dendroaspis natriuretic
      peptide (DNP) on calcium-activated potassium current (I K(Ca)) and its mechanism
      in gastric antral circular smooth muscle cells (SMCs) using the whole-cell patch
      clamp technique. DNP concentration-dependently increased macroscopic I K(Ca) and
      spontaneous transient outward currents (STOCs) in freshly isolated guinea pig
      gastric antral circular SMCs. The effects of DNP on I K(Ca) and/or STOCs were not
      blocked by applying calcium-free bath solution or the ryanodine receptor (RyR)
      antagonist ryanodine (10 microM), but they were inhibited by the inositol
      triphosphate receptor (IP3R) inhibitor heparin or the guanylate cyclase inhibitor
      LY83583. Moreover, a DNP-induced increase in STOCs was potentiated by the cyclic
      guanosine monophosphate (cGMP)-sensitive phosphoesterase inhibitor zaprinast. In
      conclusion, our results suggest that DNP increases I K(Ca) in gastric antral
      circular SMCs by increasing cGMP production and activating IP3Rs.

PMID- 18096109
TI  - The role of motivational and volitional factors for self-regulated running
      training: associations on the between- and within- person level.
AB  - OBJECTIVES: Most studies examine associations between social-cognitive variables
      and self-regulated behavioural change across two or three occasions only. This
      study adopts an innovative perspective by analysing associations across 11
      occasions, which allows examining patterns of associations both on the between-
      and within-person levels. METHOD: Thirty initially untrained participants of a
      running training programme completed 11 monthly questionnaires. All
      questionnaires assessed motivational and volitional variables and self-reported
      running. Additionally, net running time of marathon, or half-marathon distance at
      the end of programme, was available. RESULTS: Self-efficacy turned out to be
      associated with intentions on the between- and within-person levels. Individual
      differences in change patterns and within-person fluctuations in volitional
      variables, intentions, and self-efficacy turned out to be consistently associated
      with change patterns and within-person fluctuations in self-regulated running
      training over time and with successfully running marathon or half-marathon
      distance. CONCLUSIONS: In contrast to examining only one facet of change, this
      study is the first to differentiate two components of change in health behaviour
      self-regulation: a systematic trend component, and a component representing
      within-person unsystematic fluctuations. Thus, results of the present study
      provide a comprehensive picture of the dynamic relations between motivational,
      volitional, and behavioural characteristics which occur between and within
      persons.

PMID- 18096110
TI  - Safety and efficacy of insulin detemir basal-bolus therapy in type 1 diabetes
      patients: 14-week data from the European cohort of the PREDICTIVE study.
AB  - OBJECTIVE: PREDICTIVE is a multi-national, prospective, observational study,
      assessing the safety and efficacy of insulin detemir in patients with diabetes.
      RESEARCH DESIGN AND METHODS: The European cohort includes 20,531 patients with
      diabetes (7420 type 1) from 11 countries. A subgroup of 4782 type 1 patients were
      transferred from a basal-bolus regimen with NPH insulin (n = 3117) or insulin
      glargine (n = 1665) to insulin detemir basal-bolus therapy; or from a human
      insulin basal-bolus regimen (n = 570) to insulin detemir/insulin aspart (part of
      the pre-study NPH group). Mean follow-up was 14.4 weeks. The primary endpoint was
      serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary
      endpoints were: incidence of overall and nocturnal hypoglycaemia; haemoglobin
      A(1c) (HbA(1c)); fasting glucose; within-patient fasting glucose variability; and
      change in body weight. RESULTS: SADRs were reported by 62 (2.0%) patients
      previously receiving NPH insulin, 45 (2.7%) patients previously receiving insulin
      glargine and seven (1.2%) patients previously receiving human basal-bolus
      insulins. Major hypoglycaemia was significantly reduced in NPH insulin (55%),
      insulin glargine (51%), and human basal-bolus insulin groups (54%; p < 0.0001 for
      all). Total and nocturnal hypoglycaemic episodes were also significantly reduced
      in all groups (p < 0.0001 for all). HbA(1c) was reduced in patients previously
      receiving NPH insulin (0.5%), insulin glargine (0.4%), and human basal-bolus
      insulins (0.6%; p < 0.0001 for all). Mean fasting glucose and within-patient
      fasting glucose variability significantly decreased in all patients (p < 0.0001
      for all). Body weight remained stable. CONCLUSIONS: In this open-label,
      prospective, observational study, insulin detemir basal-bolus therapy improved
      glycaemic control and reduced hypoglycaemia with weight neutrality in type 1
      patients in actual clinical practice.

PMID- 18096111
TI  - Mammographic breast density by area of residence: possible evidence of higher
      density in urban areas.
AB  - OBJECTIVES: A comparison of mammographic breast densities of women living in
      London with those of women living in rural and suburban areas. DESIGN AND
      METHODS: Using the standard four American College of Radiology Breast Imaging
      Reporting and Data System (BIRADS) categories of mammographic density, 318
      mammograms of women from London and 654 mammograms of women from outside the
      capital aged 27-87 years who had received mammography at the Princess Grace
      Hospital, London, were assessed for density. The association between having any
      dense tissue and area of residence was assessed using both ordered and standard
      logistic regression, giving odds ratio estimates of relative risk of dense tissue
      adjusting for age. RESULTS: Adjusting for age, London residents had significantly
      higher levels of density (OR = 1.32, 95% CI 1.04-1.70, p = 0.02). The major
      difference occurred in the age group 45-54 years and was most strongly manifested
      as a higher rate in London for density of 25% or more (BIRADS categories 2-4) as
      compared to almost entirely fatty (BIRADS 1) (OR = 2.22, 95% CI 1.05-4.68, p =
      0.035). CONCLUSION: The higher density is likely to be due to a different
      prevalence of risk factors in the London population. This study cannot ascertain
      the reason for the higher density in this urban population, but the result is a
      cause for concern given that screening uptake is lower in London. Increased
      attention to screening in urban areas and attention to screening quality for
      dense breast tissue might be prudent.

PMID- 18096112
TI  - Parameter expansion for estimation of reduced rank covariance matrices.
AB  - Parameter expanded and standard expectation maximisation algorithms are described
      for reduced rank estimation of covariance matrices by restricted maximum
      likelihood, fitting the leading principal components only. Convergence behaviour
      of these algorithms is examined for several examples and contrasted to that of
      the average information algorithm, and implications for practical analyses are
      discussed. It is shown that expectation maximisation type algorithms are readily
      adapted to reduced rank estimation and converge reliably. However, as is well
      known for the full rank case, the convergence is linear and thus slow. Hence,
      these algorithms are most useful in combination with the quadratically convergent
      average information algorithm, in particular in the initial stages of an
      iterative solution scheme.

PMID- 18096113
TI  - A rapid conditional enumeration haplotyping method in pedigrees.
AB  - Haplotyping in pedigrees provides valuable information for genetic studies (e.g.,
      linkage analysis and association study). In order to identify a set of haplotype
      configurations with the highest likelihoods for a large pedigree with a large
      number of linked loci, in our previous work, we proposed a conditional
      enumeration haplotyping method which sets a threshold for the conditional
      probabilities of the possible ordered genotypes at every unordered individual
      marker to delete some ordered genotypes with low conditional probabilities and
      then eliminate some haplotype configurations with low likelihoods. In this
      article we present a rapid haplotyping algorithm based on a modification of our
      previous method by setting an additional threshold for the ratio of the
      conditional probability of a haplotype configuration to the largest conditional
      probability of all haplotype configurations in order to eliminate those
      configurations with relatively low conditional probabilities. The new algorithm
      is much more efficient than our previous method and the widely used software
      SimWalk2.

PMID- 18096114
TI  - Selection for uniformity in livestock by exploiting genetic heterogeneity of
      residual variance.
AB  - In some situations, it is worthwhile to change not only the mean, but also the
      variability of traits by selection. Genetic variation in residual variance may be
      utilised to improve uniformity in livestock populations by selection. The
      objective was to investigate the effects of genetic parameters, breeding goal,
      number of progeny per sire and breeding scheme on selection responses in mean and
      variance when applying index selection. Genetic parameters were obtained from the
      literature. Economic values for the mean and variance were derived for some
      standard non-linear profit equations, e.g. for traits with an intermediate
      optimum. The economic value of variance was in most situations negative,
      indicating that selection for reduced variance increases profit. Predicted
      responses in residual variance after one generation of selection were large, in
      some cases when the number of progeny per sire was at least 50, by more than 10%
      of the current residual variance. Progeny testing schemes were more efficient
      than sib-testing schemes in decreasing residual variance. With optimum traits,
      selection pressure shifts gradually from the mean to the variance when
      approaching the optimum. Genetic improvement of uniformity is particularly
      interesting for traits where the current population mean is near an intermediate
      optimum.

PMID- 18096115
TI  - Detection of quantitative trait loci for reproduction and production traits in
      Large White and French Landrace pig populations.
AB  - A genome-wide scan was performed in Large White and French Landrace pig
      populations in order to identify QTL affecting reproduction and production
      traits. The experiment was based on a granddaughter design, including five Large
      White and three French Landrace half-sib families identified in the French
      porcine national database. A total of 239 animals (166 sons and 73 daughters of
      the eight male founders) distributed in eight families were genotyped for 144
      microsatellite markers. The design included 51 262 animals recorded for
      production traits, and 53 205 litter size records were considered. Three
      production and three reproduction traits were analysed: average backfat thickness
      (US_M) and live weight (LWGT) at the end of the on-farm test, age of candidates
      adjusted at 100 kg live weight, total number of piglets born per litter, and
      numbers of stillborn (STILLp) and born alive (LIVp) piglets per litter. Ten QTL
      with medium to large effects were detected at a chromosome-wide significance
      level of 5% affecting traits US_M (on SSC2, SSC3 and SSC17), LWGT (on SSC4),
      STILLp (on SSC6, SSC11 and SSC14) and LIVp (on SSC7, SSC16 and SSC18). The number
      of heterozygous male founders varied from 1 to 3 depending on the QTL.

PMID- 18096116
TI  - Genes influencing milk production traits predominantly affect one of four
      biological pathways.
AB  - In this study we introduce a method that accounts for false positive and false
      negative results in attempting to estimate the true proportion of quantitative
      trait loci that affect two different traits. This method was applied to data from
      a genome scan that was used to detect QTL for three independent milk production
      traits, Australian Selection Index (ASI), protein percentage (P%) and fat
      percentage corrected for protein percentage (F% - P%). These four different
      scenarios are attributed to four biological pathways: QTL that (1) increase or
      decrease total mammary gland production (affecting ASI only); (2) increase or
      decrease lactose synthesis resulting in the volume of milk being changed but
      without a change in protein or fat yield (affecting P% only); (3) increase or
      decrease protein synthesis while milk volume remains relatively constant
      (affecting ASI and P% in the same direction); (4) increase or decrease fat
      synthesis while the volume of milk remains relatively constant (affecting F% - P%
      only). The results indicate that of the positions that detected a gene, most
      affected one trait and not the others, though a small proportion (2.8%) affected
      ASI and P% in the same direction.

PMID- 18096117
TI  - Estimation by simulation of the efficiency of the French marker-assisted
      selection program in dairy cattle.
AB  - The efficiency of the French marker-assisted selection (MAS) was estimated by a
      simulation study. The data files of two different time periods were used: April
      2004 and 2006. The simulation method used the structure of the existing French
      MAS: same pedigree, same marker genotypes and same animals with records. The
      program simulated breeding values and new records based on this existing
      structure and knowledge on the QTL used in MAS (variance and frequency).
      Reliabilities of genetic values of young animals (less than one year old)
      obtained with and without marker information were compared to assess the
      efficiency of MAS for evaluation of milk, fat and protein yields and fat and
      protein contents. Mean gains of reliability ranged from 0.015 to 0.094 and from
      0.038 to 0.114 in 2004 and 2006, respectively. The larger number of animals
      genotyped and the use of a new set of genetic markers can explain the improvement
      of MAS reliability from 2004 to 2006. This improvement was also observed by
      analysis of information content for young candidates. The gain of MAS reliability
      with respect to classical selection was larger for sons of sires with genotyped
      progeny daughters with records. Finally, it was shown that when superiority of
      MAS over classical selection was estimated with daughter yield deviations
      obtained after progeny test instead of true breeding values, the gain was
      underestimated.

PMID- 18096118
TI  - Biodiversity of pig breeds from China and Europe estimated from pooled DNA
      samples: differences in microsatellite variation between two areas of
      domestication.
AB  - Microsatellite diversity in European and Chinese pigs was assessed using a pooled
      sampling method on 52 European and 46 Chinese pig populations. A Neighbor Joining
      analysis on genetic distances revealed that European breeds were grouped together
      and showed little evidence for geographic structure, although a southern European
      and English group could tentatively be assigned. Populations from international
      breeds formed breed specific clusters. The Chinese breeds formed a second major
      group, with the Sino-European synthetic Tia Meslan in-between the two large
      clusters. Within Chinese breeds, in contrast to the European pigs, a large degree
      of geographic structure was noted, in line with previous classification schemes
      for Chinese pigs that were based on morphology and geography. The Northern
      Chinese breeds were most similar to the European breeds. Although some overlap
      exists, Chinese breeds showed a higher average degree of heterozygosity and
      genetic distance compared to European ones. Between breed diversity was even more
      pronounced and was the highest in the Central Chinese pigs, reflecting the
      geographically central position in China. Comparing correlations between genetic
      distance and heterozygosity revealed that China and Europe represent different
      domestication or breed formation processes. A likely cause is a more diverse wild
      boar population in Asia, but various other possible contributing factors are
      discussed.

PMID- 18096119
TI  - Genetic and metabolic aspects of androstenone and skatole deposition in pig
      adipose tissue: a review.
AB  - High levels of androstenone and skatole in fat tissues are considered the primary
      causes of boar taint, an unpleasant odour and flavour of the meat from non
      castrated male pigs. The aim of this article is to review our current knowledge
      of the biology and genetic control of the accumulation of androstenone and
      skatole in fat tissue. Two QTL mapping studies have shown the complexity of the
      genetic control of these traits. During the last ten years, several authors have
      taken a more physiological approach to investigate the involvement of genes
      controlling the metabolism of androstenone and skatole. Although some authors
      have claimed the identification of candidate genes, it is more appropriate to
      talk about target genes. This suggests that genes affecting androstenone and
      skatole levels will have to be sought for among specific or non-specific
      transcription factors interacting with these target genes.

PMID- 18096120
TI  - Bacterial lipopolysaccharide induces increased expression of toll-like receptor
      (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial
      cells.
AB  - Bovine mammary epithelial cells contribute to the innate immune response to
      intramammary infections by recognizing pathogens through specialized pattern
      recognition receptors. Toll-like receptor 4 (TLR4) is one such receptor that
      binds and is activated by lipopolysaccharide (LPS), a component of the outer
      envelope of Gram-negative bacteria. In this study, MAC-T cells (a bovine mammary
      epithelial cell line) were incubated in the presence or absence of increasing
      concentrations of LPS for 24 h. Expression of TLR2 and TLR4 were analyzed at both
      mRNA and protein levels by quantitative real-time PCR (qPCR) and flow cytometry,
      respectively. The mRNA of both receptors were up-regulated by all concentrations
      of LPS used (P<0.01). Similarly, flow cytometry with specific antibodies against
      TLR2 and TLR4 detected increased surface expression of these proteins.
      Furthermore, expression of downstream TLR4 signaling molecules was examined by
      qPCR following varying exposure times to 1 mug/mL of LPS. Results demonstrate
      that the required adaptor molecules and transcription factors were up-regulated
      in a time-dependent manner. Both the MyD88 dependent and independent pathways in
      TLR4 signaling were activated in MAC-T cells. Expression of TOLLIP increased in
      response to LPS as did the pro-apoptotic protease, CASP8. These results suggest
      that the bovine mammary epithelium possesses the necessary immune repertoires
      required to achieve a robust defense against E. coli. The current findings,
      coupled with previous findings that S. aureus ligands induce up-regulation of
      TLR4, may indicate a positive adaptation by mammary epithelial cells to
      effectively respond to different types of mastitis pathogens.

PMID- 18096121
TI  - Expression of toll-like receptor 2 (TLR2) in porcine leukocyte subsets and
      tissues.
AB  - Toll-like receptors (TLR) are a group of pattern recognition molecules that play
      a crucial role in innate immunity. TLR2 recognises a variety of microbial
      components leading to the development of inflammatory and immune responses. To
      characterise the expression and functional properties of porcine TLR2 (pTLR2), we
      have raised a panel of monoclonal antibodies (mAb) against this molecule. Mouse
      3T3 cell transfectants expressing pTLR2 were used for immunisation of mice. The
      specificity of these antibodies was confirmed by their reactivity with CHO cells
      transfected with pTLR2 but not with pTLR4 or with non-transfected cells. Using
      one of these mAbs, named 1H11, pTLR2 was found on cells of the innate immune
      system, including monocytes, macrophages, and granulocytes, but not on peripheral
      blood lymphocytes. Staining of tissue sections showed that pTLR2 is also
      expressed on epithelial cells lining the tracheobronchial and intestinal tracts,
      bile ducts in the liver and renal tubules, and on the basal layer of the
      epidermis. This distribution is consistent with a surveillance function at entry
      sites, allowing for early detection of microbial invasion.

PMID- 18096122
TI  - Using relational structure to detect symmetry: a Voronoi tessellation based model
      of symmetry perception.
AB  - Numerous models of symmetry perception have been proposed in recent years.
      Unfortunately, it is difficult to assess the relative utility of these models as
      little effort has been made to directly compare them. This paper outlines a new
      model of symmetry perception based upon the relational structure revealed by
      Voronoi tessellation. The model has been developed in response to evidence
      suggesting that the human visual system is generating a Voronoi-like
      representation at an early stage in processing. Bayesian model selection is
      employed to compare the performance of the Voronoi model to that of five
      previously published models across six empirical datasets. The results indicate
      that the Voronoi model provides a more likely account of the data than the five
      alternative models.

PMID- 18096123
TI  - The influence of organ acceptance criteria on long-term graft survival: outcomes
      of a kidney transplant program.
AB  - BACKGROUND: In an effort to improve our transplant program's dead-donor kidney
      acceptance criteria, we compared 2 different consecutive time periods in our
      transplant program. Period I, in which the program used more-restrictive criteria
      in accepting dead-donor kidneys for our patients, and period II, when the program
      used less-restrictive criteria for the dead-donor kidneys that were accepted. The
      less-restrictive criteria resulted in an increase in the number of renal
      transplants performed. METHODS: A retrospective database analysis was performed
      of all organ-donor offers to a single kidney transplant program from July 1,
      2004, to September 30, 2006 (period I = July 1, 2004, through July 10, 2005, and
      period II = July 11, 2005 through September 30, 2006). Kidney acceptance rates
      were compared between 2 consecutive time periods during which the program used
      different organ acceptance criteria. Data analysis included a comparison of donor
      characteristics, reason for organ refusal, creatinine clearance, and graft
      survival. Graft survival was obtained for both kidneys associated with each
      offer, even if 1 or both of the organs were transplanted at a different center.
      RESULTS: Donor age and kidney quality were the most common reasons for refusal
      during both transplant periods. The organ acceptance rate improved markedly
      during period II. There was a marked increase in the number of kidney transplants
      performed during a 12-month period when comparing the 2 periods: 16 transplants
      during period I versus 46 transplants during period II. Graft survival was not
      significantly different between the 2 periods. Calculated creatinine clearance,
      which we used as a marker of organ quality, was statistically lower during period
      II. CONCLUSIONS: Increased acceptance rate was not associated with statistically
      significant decreased graft survival. Although an increase in delayed graft
      function was associated with broader acceptance criteria, this factor did not
      affect overall graft survival. By increasing our kidney acceptance rate, we were
      able to successfully transplant more patients.

PMID- 18096124
TI  - Patterns of care analysis among women with ductal carcinoma in situ in North
      Carolina.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast comprises approximately
      25% of new breast cancer cases. The aim of this study was to delineate patterns
      of care for women with DCIS as related to age, tumor characteristics, and
      race/ethnicity. Further study goals included the identification of predictors of
      breast-conserving surgery (BCS), adjuvant radiation, and/or hormonal therapy, as
      well as breast reconstruction after mastectomy. METHODS: The North Carolina
      Cancer Registry was queried for primary DCIS treated in 1998 and 1999 (n =
      1,893). Logistic regression analysis was performed to define the determinants of
      patterns of care. RESULTS: Thirty-five percent of the women in this study sample
      underwent mastectomy. Positive predictors of mastectomy included young age (age
      <50 y vs 70+; odds ratio [OR], 1.55; 95% confidence interval [CI], 1.13-2.11) and
      larger tumor size (>2 mm vs 0-1 mm; OR, 2.43; 95% CI, 1.63-3.60). Approximately
      48% of women who underwent BCS received adjuvant radiation therapy. Factors
      associated with receiving radiation therapy after BCS include younger age (age
      <50 vs 70+; OR, 2.12; 95% CI, 1.49-3.03). Approximately 19% of women who
      underwent BCS received adjuvant hormonal therapy. Positive predictors of
      receiving adjuvant hormonal therapy after BCS included age of 50 to 60 years
      versus 70+ (OR, 2.16; 95% CI, 1.36-3.44) and the receipt of radiation therapy
      (OR, 3.60; 95% CI, 2.55-5.06). Approximately 28% of women who underwent
      mastectomy received breast reconstruction surgery. Positive predictors of breast
      reconstruction after mastectomy included age younger than 50 years versus 70+
      years (OR, 47.36; 95% CI, 19.45-115.32). African American race was associated
      negatively with receipt of breast reconstruction after mastectomy (OR, .46; 95%
      CI, .26-.84). CONCLUSIONS: Treatment strategies for primary surgical therapy for
      DCIS vary significantly by age. Inconsistencies exist surrounding the use of
      adjuvant radiation therapy after BCS in women with DCIS. Variations in approaches
      to reconstructive surgery after mastectomy may be related to age, ethnicity,
      and/or economic constraints.

PMID- 18096125
TI  - Randomized double-blinded trial investigating the impact of a curriculum focused
      on error recognition on laparoscopic suturing training.
AB  - BACKGROUND: Error recognition predicts technical skill. A curriculum including
      error recognition may improve laparoscopic suturing performance. METHODS: Thirty
      novices were randomized into 2 groups. Each viewed an instruction videotape and
      underwent timed objective structured assessments of technical skills. Group A
      practiced the task, group B viewed an error-instruction video, practiced,
      followed by re-assessment. Participants counted errors on a videotape. Data were
      analyzed with the Fisher exact text, the Wilcoxon test, and the Kendall tau test.
      RESULTS: The improvement in task time was greater in group A than in group B (P <
      .001). The objective structured assessments of technical skills scores improved
      for both groups, but did not reveal differences between the groups. Group B
      recognized significantly more errors than group A (P < 0.001). CONCLUSIONS: The
      additional error instruction showed a negative impact on performance speed, but
      improved cognitive error recognition. Whether visual memory overload influenced
      the outcome requires further examination.

PMID- 18096126
TI  - Alpha lipoic acid attenuates microvascular endothelial cell hyperpermeability by
      inhibiting the intrinsic apoptotic signaling.
AB  - BACKGROUND: This study examined whether alpha lipoic acid (ALA), an antioxidant
      with anti-apoptotic properties, synthesized in mitochondria of endothelial cells,
      would inhibit intrinsic apoptotic signaling and microvascular endothelial cell
      hyperpermeability. METHODS: Rat lung microvascular endothelial cells were
      transfected with BAK (BH3) peptide (5 microg/mL) or active caspase-3 (5
      microg/mL) and were pretreated with ALA (10 and 100 micromol/L).
      Hyperpermeability was determined using fluorescein isothiocyanate albumin-flux
      across the cells grown as monolayer. Reactive oxygen species (ROS) formation was
      determined using 123 dihydrorhodamine and mitochondrial membrane potential using
      JC-1. Cytochrome c levels and caspase-3 activity were determined using an enzyme
      linked immunosorbent assay and a fluorometric assay, respectively. RESULTS: ALA
      (100 micromol/L) pretreatment attenuated BAK (BH3)-induced hyperpermeability and
      ROS formation. ALA restored BAK (BH3)-induced collapse in mitochondrial membrane
      potential and decreased BAK (BH3)-induced cytochrome c release and caspase-3
      activity. CONCLUSIONS: These findings suggest that ALA attenuates BAK-induced
      monolayer hyperpermeability through the inhibition of ROS formation and intrinsic
      apoptotic signaling.

PMID- 18096127
TI  - Utility of bilateral bronchoalveolar lavage for the diagnosis of ventilator
      associated pneumonia in critically ill surgical patients.
AB  - BACKGROUND: Bronchoalveolar lavage (BAL) is recommended to facilitate the
      diagnosis of ventilator-associated pneumonia (VAP). It is unclear if bilateral
      sampling improves the accuracy of BAL. METHODS: Consecutive patients with
      clinical suspicion for VAP were analyzed. All patients underwent bilateral BAL. A
      threshold of >10(4) colony-forming units (cfu)/mL was diagnostic for VAP (VAP
      positive). Samples were concordant if the organism(s) and thresholds from both
      lungs were diagnostically consistent. Organisms </=10(4) cfu/mL with growth on
      the contralateral sample >10(4) cfu/mL were considered false-negative samples.
      RESULTS: Between November 2005 and April 2006, 73 patients were considered
      clinically suspicious for VAP. Forty-four (60%) patients were VAP positive.
      Twenty-eight (64%) VAP patients had concordant samples. Overall, there were 15
      false-negative samples. Sole use of the unilateral samples to guide treatment
      would have inappropriately directed antibiotic avoidance and/or discontinuation
      in 25% of VAP patients. Influence of the chest radiograph was equivocal because
      of the presence of bilateral infiltrates in 80% of discordant samples.
      CONCLUSIONS: Bilateral BAL improves the accuracy of bronchoscopy in diagnosing
      VAP. Unilateral BAL may be insensitive in patients with clinically significant
      contralateral infection.

PMID- 18096128
TI  - Cervical spine fractures in geriatric blunt trauma patients with low-energy
      mechanism: are clinical predictors adequate?
AB  - BACKGROUND: Studies have identified clinical predictors to guide radiologic
      evaluation of the cervical spine in geriatric patients. We hypothesized that
      clinical predictors are not adequate in the identification of cervical spine
      fractures in geriatric blunt trauma patients with low-energy mechanism. METHODS:
      A retrospective case-control study was performed on geriatric blunt trauma
      patients sustaining low-energy trauma from January 2000 to January 2006. A data
      form including 8 clinical predictors was completed for each group. RESULTS: There
      were 35 study and 64 control patients identified. Both groups were similar in age
      (study 83.6 vs control 81.2) and injury severity score (study 9.06 vs control
      9.61). Only neck tenderness exceeded the expected occurrence in the presence of a
      cervical spine injury (chi(2) = 18.1, P = .001) in just 45.5% of the study group.
      CONCLUSIONS: Clinical predictors appear inadequate for the evaluation of the
      cervical spine in geriatric trauma patients with low-energy mechanism.

PMID- 18096129
TI  - [Middle aortic syndrome: a case report].
AB  - Middle aortic syndrome (MAS) results from a diffuse narrowing of the distal
      thoracic or abdominal aorta commonly involving both the visceral and renal
      arteries. Congenital, acquired, inflammatory, and infectious etiologies have been
      described. Symptoms typically occur within the first three decades of life and
      include hypertension, lower extremity claudication, and mesenteric ischemia. The
      condition is considered a life-threatening emergency as a result of the
      complications associated with severe hypertension. Diagnosis is made with
      magnetic resonance and computed tomography angiography. Surgical bypass grafting
      is the optimal method of treatment and must be tailored depending on the
      distribution of disease. We report one case of MAS treated with thoracic aorta to
      abdominal aorta bypass and reimplantation of the right renal artery.

PMID- 18096130
TI  - [Retroperitoneal laparoscopic adrenalectomy in a pregnant woman presenting MEN2a
      with a pheochromocytoma: case report and review of the literature].
AB  - The diagnosis of pheochromocytoma during pregnancy is uncommon and is at high
      risk for both mother and baby. We report the case of a 22-year-old woman with
      MEN2a (mutation C634Y in exon 11 of RET) who had undergone surgery for medullary
      carcinoma of the thyroid and hyperparathyroidism when she was 18. She was
      asymptomatic when she was seen at 22 weeks of gestation because of increased
      urinary metanephrine levels. A 24-h blood pressure monitoring was normal.
      Abdominal magnetic resonance imaging (MRI) revealed a right-sided, 34x31x28mm,
      well-limited, adrenal mass with high signal intensity on T2-weighted images; the
      contralateral adrenal was normal. At 26 weeks of gestation and after an adequate
      labetalol preparation, a retroperitoneal laparoscopic right-sided adrenalectomy
      was performed without maternal or foetal complications. Pathohistological
      examination confirmed the presence of a 3cm pheochromocytoma in the right adrenal
      gland, with no sign of malignancy. The levels of urinary methoxylated metabolites
      were normal two months after surgery. The pregnancy progressed normally and the
      patient delivered a healthy child without complications. In conclusion, firstly,
      all MEN2a women should be screened for a pheochromocytoma with a 24-h urinary
      metanephrine and normetanephrine evaluation before or early during pregnancy,
      even with normal blood pressure; secondly, pheochromocytoma diagnosed during
      pregnancy should be operated on during pregnancy because of the risks for both
      mother and baby; thirdly, after medical therapy, retroperitoneal laparoscopic
      adrenalectomy can be performed during the second trimester of pregnancy.

PMID- 18096131
TI  - The effect of floor slope on sub-maximal lifting capacity and technique.
AB  - Inclined surfaces, where both the lifter and load are on the slope, may be
      encountered in a jobsite situation. The purpose of this study was to determine if
      facing up or down a sloped surface (10 degrees and 20 degrees ) would affect
      maximal acceptable weights of lift (MAWL) using a 10 min psychophysical approach
      with symmetric freestyle technique at 4 lifts/min. Seventeen healthy men and 18
      women determined floor to knuckle height MAWL while facing uphill, downhill, and
      on a level surface. Motion capture was also performed to examine sagittal plane
      joint angles and foot placement relative to a milk crate. Slope did not alter
      MAWL (p>0.05) with the men lifting more than the women in every condition
      (p<0.001) (25 kg vs. 15 kg, respectively). Foot placement relative to the box was
      altered by slope such that both horizontal position behind and vertical position
      below the box increased as slope changed from the downhill to uphill conditions
      (both p<0.001). Forward torso lean as well as hip, knee, and ankle (plantar)
      flexion generally decreased as slope changed from the downhill to uphill
      conditions (all p<0.001). Torso and knee motion appeared to be protected compared
      to the other joints, changing the least. Though trends were the same in both
      sexes, interactions did exist in vertical foot position and hip angle (both
      p0.001). In conclusion, the body is highly adaptive to floor slope, maintaining
      MAWL at least in the short term. However, while slight technique differences
      exist between men and women, care should be taken by all when facing uphill due
      to the tendency to stand further from the load horizontally and when facing
      downhill due to increased torso lean.

PMID- 18096132
TI  - Assessing the value of human factors initiatives.
AB  - This paper examines the effectiveness of human factors initiatives and addresses
      some difficulties reported in calculating the value of such interventions.
      Company representatives and researchers applied a novel probabilistic assessment
      tool to estimate the financial impact of two macro-ergonomic projects. Key
      benefits of the company intranet project include reduced administrative and
      operational costs compared to a paper-based system; time savings for users asking
      for, providing and receiving information; and improved system usability and
      higher levels of usage. The communities of practice project demonstrates value
      through more efficient distribution and retrieval of information; reduced
      duplication by re-using technical knowledge to solve similar problems and
      improved sharing of good working practices, lessons and resources. The strengths
      of the tool include transparency, being quick and easy to learn and the
      collaborative workshop format, involving researches and key representatives from
      the organization. It makes a useful contribution to the challenge of assessing
      the financial value of ergonomic interventions, and, by exploiting its diagnostic
      and planning capabilities, could be extended to other domains.

PMID- 18096133
TI  - A comparison of human jaw muscle cross-sectional area and volume in long- and
      short-face subjects, using MRI.
AB  - OBJECTIVE: In humans, the vertical craniofacial dimensions vary significantly
      with the size of the jaw muscles, which are regarded as important controlling
      factors of craniofacial growth. The functional relevance of the maximum cross
      sectional area (CSA), indicating maximum muscle strength, is questionable since
      peak forces are generated only a fraction of the day. Alternatively, muscle
      volume (indicating the generated loads) might be a more meaningful functional
      variable. Therefore, the aim of this study was to investigate if jaw muscle
      volume is stronger related with vertical craniofacial dimensions than with jaw
      muscle CSA. DESIGN: Thirty-one adult healthy subjects with varying vertical
      craniofacial morphology participated in this study. Axial magnetic resonance
      imaging (MRI) scans were used for segmentation of the masseter (Mas) and medial
      pterygoid muscles (MPM). This enabled measurements of the muscle CSA and volume.
      Cephalometric analysis was performed using lateral radiographs. With factor
      analysis, the number of cephalometric variables was reduced into two factors that
      represented the anterior face height and the posterior face height (PFH),
      respectively. Subsequently, mutual relationships between these factors and
      muscular variables were assessed using a multiple regression analysis. RESULTS:
      It was found that vertical craniofacial dimensions were significantly better (up
      to 12%) related with muscle volume rather than with CSA. Furthermore, it was
      shown that especially the PFH factor was significantly correlated with the Mas
      and MPM. CONCLUSION: Vertical craniofacial dimensions are stronger related with
      jaw muscle volume than with CSA. Tentatively, it can be assumed that the
      generated muscle loads, rather than maximum forces, influence vertical
      craniofacial growth.

PMID- 18096134
TI  - Differences in motilin receptor desensitization after stimulation with motilin or
      motilides are due to alternative receptor trafficking.
AB  - BACKGROUNDS & AIMS: The motilin receptor (MTLR) is an important therapeutic
      target for treatment of hypomotility disorders. The negative outcome in clinical
      trials with the motilin agonist, ABT-229, indicated that desensitization may
      limit the therapeutic usefulness of motilides. We therefore compared the
      mechanisms involved in the intracellular trafficking of the MTLR after
      stimulation with motilin, erythromycin-A (EM-A) or ABT-229. METHODS:
      Desensitization was studied by measuring changes in Ca2+ rises and by receptor
      binding studies in CHO cells co-expressing the Ca2+ indicator apoaequorin and the
      MTLR, C-terminally tagged with EGFP. Receptor phosphorylation was studied by
      immunoprecipitation. MTLR-EGFP trafficking to organelles and translocation of
      beta-arrestins were visualized by fluorescence microscopy. RESULTS: Agonist
      induced desensitization of the MTLR was due to receptor internalization with
      potencies (p-int50) in the order of: ABT-229 (8.3)>motilin (7.86)>EM-A (4.77) but
      with no differences in the internalization kinetics (t(1/2): approximately 25
      min). The percentage cell surface receptor loss was more profound after exposure
      to ABT-229 (88+/-1%) than to motilin (63+/-10%) or EM-A (34+/-2%). For motilin
      and EM-A MTLR phosphorylation probably occurs via G protein-coupled receptor
      kinases while for ABT-229 phosphorylation was also protein kinase C dependent.
      All agonists translocated cytosolic beta-arrestin-2 with greater affinity to the
      plasma membrane than beta-arrestin-1. After internalization the MTLR co-localized
      with transferrin but not with cathepsin D. After stimulation with motilin and EM
      A the t(1/2) for MTLR resensitization was 3h and 1h, respectively but amounted
      26h for ABT-229. CONCLUSION: Our results suggest that the resensitization
      kinetics determine the desensitization properties of the motilin agonists.

PMID- 18096135
TI  - Priming by lipopolysaccharide exaggerates acute lung injury and mortality in
      responses to peptidoglycan through up-regulation of Toll-like receptor-2
      expression in mice.
AB  - Invasive infection mixed with Gram-positive and Gram-negative bacteria often
      results in severe sepsis and septic shock, the prognosis of which is extremely
      poor and the mortality is high. Here, we hypothesized that lipopolysaccharide
      (LPS) from Gram-negative bacteria may exert a priming effect on the innate immune
      response to peptidoglycan (PepG) from Gram-positive bacteria and if so, examined
      the molecular mechanism of this priming. We found that mice who underwent
      intratracheal instillation with PepG (5 mg/kg) following prior administration of
      LPS (5 mg/kg) had a marked decline in survival as compared with the animals given
      each bacterial cell wall component alone. Furthermore, blood gas exchange
      impairment and pulmonary vascular hyperpermeability were greatly enhanced in mice
      given PepG after LPS stimulation, indicating a severe development of acute lung
      injury. LPS significantly up-regulated the expression levels of Toll-like
      receptor (TLR)-2 mRNA and protein in mouse lungs. Translocation of TLR-2 to the
      membranes was also increased by LPS stimulation. This was supported by
      immunohistochemical examination showing that TLR-2 expression was changed from
      the cytoplasm to the luminal surface of bronchiolar epithelial cells following
      LPS stimulation. We also demonstrated an LPS-induced increase in TLR-2 mRNA
      expression in type-II pneumocytes by reverse transcription-polymerase chain
      reaction following laser-assisted microdissection. In vivo transfection of
      nuclear factor-kappaB (NF-kappaB) oligonucleotides strongly prevented the up
      regulation of TLR-2 after LPS stimulation at pulmonary cellular and tissue
      levels. We conclude that the priming effect of LPS on PepG-induced lung injury
      and death is preceded by NF-kappaB-mediated up-regulation of TLR-2.

PMID- 18096136
TI  - Metabolic transformation has a profound effect on anti-inflammatory activity of
      flavonoids such as quercetin: lack of association between antioxidant and
      lipoxygenase inhibitory activity.
AB  - Dietary flavonoids are thought to have health benefits possibly due to
      antioxidant and anti-inflammatory properties. Many previous in vitro studies
      examining the bioactivity of flavonoids have failed to consider the effects of
      metabolic transformation on flavonoid activity. In this study we examined the
      effect of quercetin and its major metabolites on the production of pro
      inflammatory eicosanoids by human leukocytes. Studies comparing free radical
      scavenging, antioxidant activity and eicosanoid production demonstrate that there
      are different structural requirements for antioxidant and anti-inflammatory
      activity. We also investigated the effect of metabolic transformation on
      flavonoid bioactivity by comparing the activity of quercetin and its major
      metabolites to inhibit inflammatory eicosanoid production from human leukocytes.
      Quercetin was a potent inhibitor of leukotriene B4 formation in leukocytes (IC50
      approximately 2 microM), and its activity was dependent on specific structural
      features, particularly the 2,3-double bond of the C-ring. Functionalisation of
      the 3'-OH group with either methyl or sulfate reduced inhibitory activity up to
      50% while a glucuronide substituent at the 3-OH effectively removed the LTB4
      inhibitory activity. The major quercetin metabolite quercetin-3'-O-sulfate
      retained considerable lipoxygenase inhibitory activity (IC50 approximately 7
      microM) while quercetin-3-O-glucuronide maintained antioxidant activity but had
      no lipoxygenase inhibitory activity at physiological concentrations. In
      conclusion, we have found that structural modification of quercetin due to
      metabolic transformation had a profound effect on bioactivity, and that the
      structural features required for antioxidant activity of quercetin and related
      flavonoids were unrelated to those required for inhibition of inflammatory
      eicosanoids.

PMID- 18096137
TI  - A placebo-controlled trial of bupropion combined with nicotine patch for smoking
      cessation in schizophrenia.
AB  - BACKGROUND: Individuals with schizophrenia smoke at higher rates (58%-88%) than
      the general population (approximately 22%), and have difficulty quitting. We
      determined whether the combination of sustained-release (SR) bupropion (BUP) with
      the transdermal nicotine patch (TNP) was well-tolerated and superior to placebo
      (PLO)+TNP for smoking cessation in schizophrenia. METHODS: A 10-week, double
      blind, placebo-controlled trial of BUP (300 mg/day) in combination with TNP (21
      mg/24h) for 58 outpatient smokers with schizophrenia was conducted. Primary
      outcome measures were continuous smoking abstinence in the last 4 weeks of the
      trial (Days 43-70) and 7-day point prevalence abstinence at 6 months post-target
      quit date (TQD) (week 26). RESULTS: Smokers assigned to the BUP+TNP group (n =
      29) were more likely to achieve continuous smoking abstinence (8/29, 27.6%) than
      the PLO+TNP group (n = 29, 1/29, 3.4%) [Fisher's Exact Test, p < .05]; at 6
      months post-TQD, 4/29 (13.8%) versus 0/29 (0.0%) achieved 7-day point prevalence
      smoking abstinence (p = .11). Neither bupropion SR nor smoking abstinence
      significantly altered the positive or negative symptoms of schizophrenia. The
      combination was well-tolerated in smokers with schizophrenia. CONCLUSIONS:
      Combination therapy with bupropion SR+TNP versus placebo+TNP is well-tolerated
      and significantly improved short-term smoking abstinence in smokers with
      schizophrenia.

PMID- 18096138
TI  - Expression and localization of Fas-associated proteins following focal cerebral
      ischemia in rats.
AB  - The aim of this study was to investigate the changes of expression of Fas
      associated proteins and its cellular localization in the peri-infarct region
      following transient focal cerebral ischemia. Adult male Sprague-Dawley rats
      underwent right middle cerebral artery occlusion (MCAo) for 2 h and reperfusion
      for 1, 3, 6, 12 and 24 h. The expression of Fas-associated death domain protein
      (FADD), Fas-associated phosphatase-1 (FAP-1) caspase-8 and death-associated
      protein (Daxx), the pro-apoptotic genes, were examined by methods of RT-PCR,
      immunohistochemistry and Western blot. The results showed that the expression
      levels of mRNA and protein for FADD and caspase-8 increased significantly at 1-3
      h after reperfusion, peaked at 12 h, then declined markedly at 24 h. The time
      course change of FAP-1 was consistent with that of FADD. The expression level of
      mRNA and protein for death-associated protein (Daxx) increased significantly at 3
      h after reperfusion and persisted for 24 h at a high level. Immunofluorescence
      double-staining laser scanning showed that the immunoreactivity of FADD was
      localized in cytoplasm, and Daxx immunoreactivity was translocated from nucleus
      to cytoplasm at 3 h after reperfusion. The TUNEL-positive cells could be found in
      peri-infarct region at 3 h and increased with time after reperfusion. Our
      findings suggest a possible association between expression of FADD, caspase-8,
      Daxx and FAP-1 genes and apoptosis following ischemia.

PMID- 18096139
TI  - Segmental processing in the human auditory dorsal stream.
AB  - In the present study we investigated the functional organization of sublexical
      auditory perception with specific respect to auditory spectro-temporal processing
      in speech and non-speech sounds. Participants discriminated verbal and nonverbal
      auditory stimuli according to either spectral or temporal acoustic features in
      the context of a sparse event-related functional magnetic resonance imaging
      (fMRI) study. Based on recent models of speech processing, we hypothesized that
      auditory segmental processing, as is required in the discrimination of speech and
      non-speech sound according to its temporal features, will lead to a specific
      involvement of a left-hemispheric dorsal processing network comprising the
      posterior portion of the inferior frontal cortex and the inferior parietal lobe.
      In agreement with our hypothesis results revealed significant responses in the
      posterior part of the inferior frontal gyrus and the parietal operculum of the
      left hemisphere when participants had to discriminate speech and non-speech
      stimuli based on subtle temporal acoustic features. In contrast, when
      participants had to discriminate speech and non-speech stimuli on the basis of
      changes in the frequency content, we observed bilateral activations along the
      middle temporal gyrus and superior temporal sulcus. The results of the present
      study demonstrate an involvement of the dorsal pathway in the segmental
      sublexical analysis of speech sounds as well as in the segmental acoustic
      analysis of non-speech sounds with analogous spectro-temporal characteristics.

PMID- 18096141
TI  - Impact of an acute exposure to ethanol on the oxidative stress status in the
      hippocampus of prenatal restraint stress adolescent male rats.
AB  - Prenatal restraint stress (PRS) in rats is associated with hippocampal
      dysfunctions and several behavioural and endocrine disorders related to this
      brain area. Recently, we have reported that the PRS modifies the hypothalamic
      pituitary-adrenal (HPA) response to an ethanol challenge in adolescent animals.
      Since hippocampus is particularly sensitive to the deleterious effects of ethanol
      during adolescence, we investigated in this study the combined effects of PRS and
      ethanol administration on the oxidative status in the hippocampus of 28-day-old
      male rats. Thirty minutes after an intraperitoneal (i.p.) injection of ethanol
      (1.5 g/kg), the activities of several antioxidant enzymes (superoxide dismutase,
      catalase and glutathione peroxidase) but also non-enzymatic antioxidant (reduced
      glutathione) were assayed. Thiobarbituric acid reactive substances (TBARS) levels
      were also measured as a marker of lipid peroxidation. Ethanol enhanced superoxide
      dismutase activity in control rats but not in PRS rats. At basal level, catalase
      activity was lower in PRS rats than in control rats, indicating a potentially
      higher sensitivity to oxidative damages after this early stress. However, the
      hippocampal TBARS levels were not significantly affected by the ethanol
      administration, showing that an acute ethanol exposure does not induce oxidative
      damage in adolescent male rats. In conclusion, our data suggest that PRS affects
      both basal antioxidant status in the hippocampus and antioxidant response after
      an acute ethanol exposure. These findings extend previous works showing that PRS
      leads to hippocampal dysfunctions and raise the question of the potential
      increase of the hippocampal oxidative damage in PRS rats after repeated exposure
      to ethanol.

PMID- 18096140
TI  - Decreased spinal cord opioid receptor mRNA expression and antinociception in a
      Theiler's murine encephalomyelitis virus model of multiple sclerosis.
AB  - Multiple sclerosis patients typically experience increased pain that is
      relatively insensitive to opiate treatment. The mechanistic basis for this
      increased nociception is currently poorly understood. In the present study, we
      utilized the Theiler's murine encephalomyelitis virus (TMEV) model of MS to
      examine possible changes in spinal cord opioid receptor mRNA over the course of
      disease progression. TMEV infection led to significantly decreased mu, delta and
      kappa opioid receptor mRNA expression as analyzed by quantitative real-time PCR
      in both male and female mice at days 90, 150 and 180 post-infection (PI). Since
      opioid receptor mRNA expression decreased in TMEV mice, we examined whether
      opiate analgesia is also altered. TMEV infected female mice had significantly
      decreased opiate analgesia in thermal nociceptive tests beginning at day 90 PI,
      while TMEV-infected male mice did not display significantly decreased opiate
      analgesia until day 120 PI. The novel finding that opioid receptor expression is
      significantly decreased in the spinal cord of TMEV mice could explain the
      increased nociception and loss of opiate analgesia observed in both TMEV mice and
      multiple sclerosis patients.

PMID- 18096142
TI  - Factors contributing to the adaptation aftereffects of facial expression.
AB  - Previous studies have demonstrated the existence of adaptation aftereffects for
      facial expressions. Here we investigated which aspects of facial stimuli
      contribute to these aftereffects. In Experiment 1, we examined the role of local
      adaptation to image elements such as curvature, shape and orientation,
      independent of expression, by using hybrid faces constructed from either the same
      or opposing expressions. While hybrid faces made with consistent expressions
      generated aftereffects as large as those with normal faces, there were no
      aftereffects from hybrid faces made from different expressions, despite the fact
      that these contained the same local image elements. In Experiment 2, we examined
      the role of facial features independent of the normal face configuration by
      contrasting adaptation with whole faces to adaptation with scrambled faces. We
      found that scrambled faces also generated significant aftereffects, indicating
      that expressive features without a normal facial configuration could generate
      expression aftereffects. In Experiment 3, we examined the role of facial
      configuration by using schematic faces made from line elements that in isolation
      do not carry expression-related information (e.g. curved segments and straight
      lines) but that convey an expression when arranged in a normal facial
      configuration. We obtained a significant aftereffect for facial configurations
      but not scrambled configurations of these line elements. We conclude that facial
      expression aftereffects are not due to local adaptation to image elements but due
      to high-level adaptation of neural representations that involve both facial
      features and facial configuration.

PMID- 18096144
TI  - Calbindin D-28K and parvalbumin expression in embryonic chick hippocampus is
      enhanced by prenatal auditory stimulation.
AB  - Calcium-binding proteins (CaBPs) buffer excess of cytosolic Ca(2+), which
      accompanies neuronal activity following external stimuli. Prenatal auditory
      stimulation by species-specific sound and music influences early maturation of
      the auditory pathway and the behavioral responses in chicks. In this study, we
      determined the volume, total number of neurons, proportion of calbindin D-28K and
      parvalbumin-positive neurons along with their levels of expression in the
      developing chick hippocampus following prenatal auditory stimulation. Fertilized
      eggs of domestic chicks were exposed to sounds of either species-specific calls
      or sitar music at 65 dB for 15 min/h round the clock from embryonic day (E) 10
      until hatching. Hippocampi of developmental stages (E12, E16 and E20) were
      examined. With an increase in embryonic age during normal development, the
      hippocampus showed an increase in its volume, total number of neurons as well as
      in the neuron proportions and levels of expression of calbindin D-28K and
      parvalbumin. A significant increase of volume at E20 was noted only in the music
      stimulated group compared to that of their age-matched control (p<0.05). On the
      other hand, both auditory-stimulated groups showed a significant increase in the
      proportion of immunopositive neurons and the levels of expression of calbindin D
      28K and parvalbumin as compared to the control at all developmental stages
      studied (p<0.003). The increase in proportions of CaBP neurons during development
      and in the sound-enriched groups suggests an activity-dependent increase in
      Ca(2+) influx. The enhanced expression of CaBPs may help in cell survival by
      preventing excitotoxic death of neurons during development and may also be
      involved in long-term potentiation.

PMID- 18096145
TI  - GABAB receptors are required for galanin modulation of membrane properties of
      neurons in the arcuate nucleus of rats.
AB  - Galanin-mediated modulation of the arcuate nucleus (Arc) neurons is thought to be
      involved in the regulation of feeding behavior, hormone secretion, and
      reproduction. We previously reported that galanin perfusion significantly
      hyperpolarized the resting membrane potential and suppressed the spontaneous
      firing in the Arc neurons in slice preparation. In this study, we focused on the
      cellular and molecular mechanisms underlying the galanin effect. The galanin
      action is mediated by the galanin receptors (GAL1/2/3R). We found that activation
      of galanin receptors alone is not sufficient to mediate the galanin effect on
      resting membrane potential and spontaneous firing; co-activation of GABA(B)
      receptors is required for galanin to accomplish its modulation on the membrane
      properties of Arc neurons. In more details, the effect of galanin on the membrane
      properties of Arc neurons is blocked by either lowering the extracellular Ca(2+)
      or the inhibition of GABA(B) receptors with the selective GABA(B) antagonist,
      saclofen. In addition, activation of GABA(B) receptors by baclofen restored the
      galanin effect under low Ca (2+) conditions. These results suggest that GABA(B)
      receptors may serve as a molecular gate for galanin signaling, and thus can be
      targeted to manipulate the galanin-mediated physiological and behavioral
      responses.

PMID- 18096143
TI  - Alpha-chloralose is a suitable anesthetic for chronic focal cerebral ischemia
      studies in the rat: a comparative study.
AB  - alpha-Chloralose is widely used as an anesthetic in studies of the
      cerebrovasculature because it provides robust metabolic and hemodynamic responses
      to functional stimulation. However, there have been no controlled studies of
      focal ischemia in the rat under alpha-chloralose anesthesia. Artificially
      ventilated rats were prepared using 1.2-1.5% isoflurane anesthesia for filament
      occlusion of the right middle cerebral artery (MCA), and anesthesia was either
      switched to alpha-chloralose (60 mg/kg bolus, 30 mg/kg/h; n=10) or was maintained
      on 1% isoflurane (n=10). Following temporary MCA occlusion EEG was monitored from
      a screw electrode and changes in cerebral blood flow (rCBF) measured with a laser
      Doppler probe placed over the ischemic cortex. This study shows that alpha
      chloralose is a safe anesthetic for ischemia studies and provides excellent
      survival. Compared with isoflurane, the cortical and total infarct volumes are
      larger in the alpha-chloralose-anesthetized animals, while the functional outcome
      at 72 h is similar. The total duration of peri-infarct flow transients (PIFTs) is
      also significantly longer in alpha-chloralose-anesthetized animals. The average
      amplitude of the flow transients showed a good correlation with the extent of
      edema in all animals as did the total duration of non-convulsive seizures (NCS)
      in the alpha-chloralose-anesthetized animals.

PMID- 18096146
TI  - Two novel oligosaccharides isolated from a beverage produced by fermentation of a
      plant extract.
AB  - An extract from 50 kinds of fruits and vegetables was fermented to produce a new
      beverage. Natural fermentation of the extract was carried out mainly by lactic
      acid bacteria (Leuconostoc spp.) and yeast (Zygosaccharomyces spp. and Pichia
      spp.). Two new saccharides were found in this fermented beverage. The saccharides
      were isolated using carbon-Celite column chromatography and preparative high
      performance liquid chromatography. Gas liquid chromatography analysis of
      methylated derivatives as well as MALDI-TOF MS and NMR measurements were used for
      structural confirmation. The (1)H and (13)C NMR signals of each saccharide were
      assigned using 2D-NMR including COSY, HSQC, HSQC-TOCSY, CH(2)-HSQC-TOCSY, and CT
      HMBC experiments. The saccharides were identified as beta-D-fructopyranosyl-(2-
      >6)-beta-D-glucopyranosyl-(1-->3)-D-glucopyranose and beta-D-fructopyranosyl-(2-
      >6)-[beta-D-glucopyranosyl-(1-->3)]-D-glucopyranose.

PMID- 18096147
TI  - Metabolic context affects hemodynamic response to bupivacaine in the isolated rat
      heart.
AB  - Previous studies have demonstrated that the local anesthetic bupivacaine
      selectively inhibits oxidative metabolism of fatty acids in isolated cardiac
      mitochondria. In the present investigation, we compare the development of
      bupivacaine cardiotoxicity during fatty acid and carbohydrate metabolism. Hearts
      from adult male Sprague-Dawley rats were excised and retrograde perfused with a
      solution containing fatty acid (oleate or octanoate) or carbohydrate substrates
      for cardiac metabolism. An infusion of bupivacaine was initiated and sustained
      until asystole, after which full cardiac recovery was allowed. During fatty acid
      metabolism, substantially lower bupivacaine doses induced both arrhythmia (60.4+/
      11.5 microg oleate and 106.8+/-14.8 octanoate versus 153.4+/-21.4 carbohydrate;
      P<0.05) and asystole (121.0+/-30.1 microg and 171.5+/-20.2 versus 344.7+/-34.6;
      P<0.001). Dose-response analysis revealed significantly increased sensitivity to
      bupivacaine toxicity during fatty acid metabolism, indicated by lower V50 doses
      for both heart rate (70.6+/-5.6 microg oleate and 122.3+/-6.2 octanoate versus
      152.6+/-8.6) and rate-pressure product (63.4+/-5.1 microg and 133.7+/-7.9 versus
      165.1+/-12.2). Time to recovery following bupivacaine exposure was elevated in
      the fatty acid group (24.3+/-2.0 s versus 15.8+/-3.1; P<0.04). Fatty acid
      metabolism was shown to predispose the isolated heart to bupivacaine toxicity,
      confirming that the local anesthetic exerts specific effects on lipid processes
      in cardiomyocytes.

PMID- 18096148
TI  - Eye movements during multiple object tracking: where do participants look?
AB  - Similar to the eye movements you might make when viewing a sports game, this
      experiment investigated where participants tend to look while keeping track of
      multiple objects. While eye movements were recorded, participants tracked either
      1 or 3 of 8 red dots that moved randomly within a square box on a black
      background. Results indicated that participants fixated closer to targets more
      often than to distractors. However, on 3-target trials, fixation was closer to
      the center of the triangle formed by the targets more often than to any
      individual targets. This center-looking strategy seemed to reflect that people
      were grouping the targets into a single object rather than simultaneously
      minimizing all target eccentricities. Here we find that observers deliberately
      focus their eyes on a location that is different from the objects they are
      attending, perhaps as a consequence of representing those objects as a group.

PMID- 18096149
TI  - Phonotactic probability influences speech production.
AB  - Speakers are faster and more accurate at processing certain sound sequences
      within their language. Does this reflect the fact that these sequences are
      frequent or that they are phonetically less complex (e.g., easier to articulate)?
      It has been difficult to contrast these two factors given their high correlation
      in natural languages. In this study, participants were exposed to novel
      phonotactic constraints de-correlating complexity and frequency by subjecting the
      same phonological structure to varying degrees of probabilistic constraint.
      Participants' behavior was sensitive to variations in frequency, demonstrating
      that phonotactic probability influences speech production independent of phonetic
      complexity.

PMID- 18096151
TI  - Role of the spinal cord heme oxygenase-carbon monoxide-cGMP pathway in the
      nociceptive response of rats.
AB  - The aim of the present study was to investigate the role of the spinal cord heme
      oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase (sGC)-cGMP pathway
      in nociceptive response of rats to the formalin experimental nociceptive model.
      Animals were handled and adapted to the experimental environment for a few days
      before the formalin test was applied. For the formalin test 50 microl of a 1%
      formalin solution was injected subcutaneously in the dorsal surface of the right
      hind paw. Following injections, animals were observed for 1 h and flinching
      behavior was measured as the nociceptive response. Thirty min before the test,
      rats were pretreated with intrathecal injections with the HO inhibitor, zinc
      deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is known to
      induce the HO pathway. Control animals were treated with vehicles. We observed a
      significant increase in nociceptive response of rats treated with ZnDPBG, and a
      drastic reduction of flinching nociceptive behavioral response in the heme
      lysinate treated animals. Furthermore, the HO pathway seems to act via cGMP,
      since methylene blue (a sGC inhibitor) prevented the reduction of flinching
      nociceptive behavioral response caused by heme-lysinate. These findings strongly
      indicate that the HO pathway plays a spinal antinociceptive role during the
      formalin test, acting via cGMP.

PMID- 18096150
TI  - The Caenorhabditis elegans NR4A nuclear receptor is required for spermatheca
      morphogenesis.
AB  - The gene nhr-6 encodes the Caenorhabditis elegans ortholog of the NR4A nuclear
      receptor. We determined the biological functions of NHR-6 through the isolation
      and characterization of a deletion allele of nhr-6, lg6001. We demonstrate that
      nhr-6 has an essential role in the development of the C. elegans somatic gonad.
      Specifically, nhr-6 is required for the development of the hermaphrodite
      spermatheca, a somatic gonad organ that serves as the site of sperm storage and
      oocyte fertilization. Using a variety of spermatheca cell markers, we have
      determined that loss of nhr-6 function causes severe morphological defects in the
      spermatheca and associated spermathecal valves. This appears to be due to
      specific requirements for nhr-6 in regulating cell proliferation and cell
      differentiation during development of these structures. The improper development
      of these structures in nhr-6(lg6001) mutants leads to defects in ovulation and
      significantly reduced fecundity of C. elegans hermaphrodites. The phenotypes of
      nhr-6(lg6001) mutants are consistent with a role for nhr-6 in organogenesis,
      similar to the functions of its mammalian homologs.

PMID- 18096152
TI  - Suppression of allergen-induced airway inflammation and immune response by the
      peroxisome proliferator-activated receptor-alpha agonist fenofibrate.
AB  - In the present study, we have assessed the effect of the peroxisome proliferator
      activated receptor-alpha (PPARalpha) agonist fenofibrate on allergen-induced
      airway inflammation and immune response. C57BL/6 or PPARalpha knock-out
      (PPARalpha(-/-)) mice were sensitized with ovalbumin and challenged with
      ovalbumin alone or with ovalbumin+lipopolysaccharides. Fenofibrate was
      administered to allergen-exposed animals during challenge only or from the day
      prior to sensitization to the end of challenge. Inflammation and immune response
      were assessed by determining cell counts and cytokine levels in bronchoalveolar
      lavage fluids, expression of the transcription factors Gata-3 and T-bet in lung
      tissue and ovalbumin-specific IgE and IgG2a in serum. Treatment with fenofibrate
      (0.15-15 mg/day) during allergen challenge dose-dependently reduced airway
      inflammatory cell infiltrate induced by ovalbumin in C57BL/6 mice. Reduction
      reached 74.3% (P<0.001) in animals treated with 15 mg/day of the PPARalpha
      agonist, whereas this treatment failed to suppress cell infiltrate induced by
      allergen in PPARalpha(-/-) mice. In addition, when administered from the day
      prior to sensitization to the end of challenge, fenofibrate (15 mg/day) triggered
      switching of the immune response to allergen towards a Th1 profile, as evidenced
      by an increase in IgG2a levels, a reduction in IL(interleukin)-4 and IL-5
      together with an increase in interferon-gamma, and a decrease in Gata-3/T-bet
      expression ratio. Upon challenge with ovalbumin+lipopolysaccharides, sensitized
      mice developed a severe inflammatory response characterized by infiltration of
      eosinophils, neutrophils, lymphocytes and macrophages and by increased release of
      IL-4, IL-5, tumor necrosis factor-alpha, macrophage-inflammatory protein-2 and
      monocyte chemoattractant protein-1. Administration of fenofibrate during allergen
      challenge dramatically reduced all responses. In conclusion, our data clearly
      demonstrate that fenofibrate exhibits an anti-inflammatory activity in allergic
      asthma, including in severe conditions, and that the PPARalpha agonist is also
      capable of switching the immune response to allergen towards a Th1 profile when
      given from the day prior to sensitization.

PMID- 18096153
TI  - The anxiolytic-like effect of the selective 5-HT6 receptor antagonist SB-399885:
      the impact of benzodiazepine receptors.
AB  - The effect of lesion of 5-hydroxytryptamine (5-HT) neurons, produced by p
      chloroamphetamine (p-CA; 2 x 10 mg/kg), and the influence of the benzodiazepine
      receptor antagonist flumazenil (10 mg/kg) on the anticonflict action of N-[3,5
      dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide (SB
      399885), a selective 5-HT6 receptor antagonist, were investigated in the Vogel
      conflict drinking test in rats. In addition, the interaction between SB-399885
      (0.3 mg/kg) and diazepam (2.5 mg/kg) was evaluated in that test. All the
      compounds tested were administered intraperitoneally. The anticonflict activity
      produced by SB-399885 (3 mg/kg) was not modified in p-CA-pretreated rats, but it
      was totally blocked by flumazenil. Combined administration of non-active doses of
      SB-399885 (0.3 mg/kg) and diazepam (2.5 mg/kg) produced a pronounced anticonflict
      effect in rats. The present results suggest that the anticonflict activity of SB
      399885 is not conditioned by the integrity of 5-HT neurons, and that
      benzodiazepine receptors are indirectly involved in its effect, possibly due to a
      functional interaction between 5-HT6 receptors and the gamma-aminobutyric acid
      (GABA)/benzodiazepine system.

PMID- 18096154
TI  - CNS-selective noncompetitive cholinesterase inhibitors derived from the natural
      piperidine alkaloid (-)-spectaline.
AB  - LASSBio-767 [(-)-3-O-acetyl-spectaline] and LASSBio-822 [(-)-3-O-tert-Boc
      spectaline] were recently described as cholinesterase inhibitors derived from the
      natural piperidine alkaloid (-)-spectaline, obtained from the flowers of Senna
      spectabilis (Fabaceae). We investigated their mechanism of inhibition of
      acetylcholinesterase and their efficacy in reversing scopolamine-induced amnesia.
      Competition assays with the substrate acetylthiocholine showed a concentration
      dependent reduction in rat brain cholinesterase Vmax without changes in apparent
      Km. The kinetic data for LASSBio-767 and LASSBio-822 were best fit by a model of
      simple linear noncompetitive inhibition with Ki of 6.1 microM and 7.5 microM,
      respectively. A dilution assay showed a fast and complete reversal of inhibition,
      independent of incubation time. Simulated docking of the compounds into the
      catalytic gorge of Torpedo acetylcholinesterase showed interactions with the
      peripheral anionic site, but not with the catalytic triad. Anti-amnestic effects
      in mice were assessed in a step-down passive avoidance test and in the Morris
      water maze 30 min after injection of scopolamine (1 mg/kg i.p.). Saline, LASSBio
      767, or LASSBio-822 was administered 15 min before scopolamine. Both compounds
      reversed the scopolamine-induced reduction in step-down latency at 0.1 mg/kg i.p.
      LASSBio-767 reversed scopolamine-induced changes in water maze escape latency at
      1 mg/kg i.p. or p.o., while its cholinergic side effects were absent or mild up
      to 30 mg/kg i.p. (LD50 above 100 mg/kg i.p.). Thus, the (-)-spectaline
      derivatives are potent cholinergic agents in vivo, with a unique profile
      combining noncompetitive cholinesterase inhibition and CNS selectivity, with few
      peripheral side effects.

PMID- 18096155
TI  - Role of nociceptin/orphanin FQ and the pseudopeptide [Phe1Psi(CH2NH)Gly2]
      nociceptin(1-13)-NH2 and their interaction with classic opioids in the modulation
      of thermonociception in the land snail Helix aspersa.
AB  - The role in nociception of nociceptin/orphanin FQ (N/OFQ) and its receptor, the
      opioid receptor-like 1 (NOP), remains unclear because this peptide has been
      implicated in both suppression and enhancement of nociception. The present work
      characterises the effects of N/OFQ and the NOP receptor antagonist, the
      pseudopeptide [Phe(1)Psi(CH(2)NH)Gly(2)]-nociceptin(1-13)-NH(2) (Phe(1)Psi), on
      thermonociception in the snail Helix aspersa using the hot plate assay.
      Additionally, the possible interaction of each of these compounds with morphine
      or dynorphin A(1-17) and naloxone was studied. Compounds were administered into
      the hemocoel cavity of H. aspersa and the latency to the aversive withdrawal
      behaviour recorded. Dose-response and time course curves were done. N/OFQ and
      naloxone produced a similar dose-dependent pronociceptive effect; however, N/OFQ
      reached its peak effect earlier and was 30 times more potent than naloxone.
      [Phe(1)Psi(CH(2)NH)Gly(2)]-nociceptin(1-13)-NH(2) and the opioid agonists,
      morphine and dynorphin A(1-17) produced antinociception with a similar efficacy,
      but [Phe(1)Psi(CH(2)NH)Gly(2)]-nociceptin(1-13)-NH(2) reached its peak effect
      more rapidly and lasted longer than that of dynorphin A(1-17) and morphine.
      [Phe(1)Psi(CH(2)NH)Gly(2)]-nociceptin(1-13)-NH(2) was 50 times less potent than
      dynorphin A(1-17), but 30 times more potent than morphine. N/OFQ significantly
      reduced morphine and dynorphin A(1-17)-induced antinociception. Combined
      administration of low doses of [Phe(1)Psi(CH(2)NH)Gly(2)]-nociceptin(1-13)-NH(2)
      and morphine or dynorphin A(1-17) produced a potent antinociceptive effect. Sub
      effective doses of naloxone and N/OFQ also synergised to produce pronociception.
      Data suggest that these two opioid classes regulate nociception through parallel
      systems. The H. aspersa model appears as a valuable experimental preparation to
      continue the study of these opioid receptor systems.

PMID- 18096156
TI  - Characterization of NKIP: a novel, Na+/K+-ATPase interacting protein mediates
      neural differentiation and apoptosis.
AB  - Cellular differentiation and programmed cell death are tightly controlled to
      maintain tissue homeostasis and proper organ function. In a screen for apoptosis
      specific gene products, we isolated an immediate early apoptosis response gene
      from myelomonocytic stem cells that appears to play a key regulatory role in a
      number of cell types and may be of particular importance in cells of the central
      nervous system. The gene's 28 kDa protein product interacts with the C-terminal
      ectodomain of the Na+/K+-ATPase (NKA) beta 1 subunit and was therefore named NKIP
      (NKA Interacting Protein). NKIP is coexpressed with NKA, localizes to lysosomes
      and the endoplasmic reticulum and is predominantly expressed in excitable tissues
      including polarized epithelia and the central nervous system. NKIP has been
      characterized as an endogenous suppressor of the NKA as reduction of NKIP in PC12
      cells significantly increases NKA activity. In pluripotent NT2 progenitor cells,
      NKIP induced rapidly K+-level-dependent cell death. NKIP overexpression induced
      growth factor-independent neurite outgrowth, which was associated with MEK
      independent phosphorylation of the transcription factor ERK1/2. Thus, we have
      identified NKIP as an important novel protein that interacts to the NKA complex,
      influencing cellular ion balance, induction of apoptosis and neuronal
      differentiation.

PMID- 18096158
TI  - Analysis of visual pigment by fundus autofluorescence.
AB  - This study investigated changes of short-wavelength fundus autofluorescence (SW
      AF) by retinal bleaching effects. All measurements were performed with the
      Heidelberg Retina Angiograph 2 (HRA 2). Initially, experimental imaging was done
      on a healthy eye after dark adaptation. Photopigment was bleached within the
      central 30 degrees of the fundus by HRA 2 excitation light. Then SW-AF imaging of
      this region was performed, and SW-AF of the surrounding, unbleached 25 degrees
      fundus region was subsequently studied by a wide-field lens. Next, another 30
      degrees SW-AF image of the posterior pole was obtained after complete dark
      adaptation. Then an extra SW-AF examination was performed with 15 degrees
      temporal eccentricity, overlapping the original examination area. Finally, a
      successive image series was carried out on the dark-adapted eye to test for
      bleaching kinetics. The second and third experiments were also performed on eyes
      with macular dystrophies. Distinct regions of increased SW-AF were observed after
      strong illumination with the blue excitation light in all eyes studied. During
      light adaptation mean gray levels showed a saturation plateau after an initial
      steep increase. The resulting gray-value maps showed significant differences of
      pixel intensities between bleached and unbleached parts of the fundus. Two
      dimensional density difference maps allowed analysis of visual pigment
      distribution and density in both healthy eyes and eyes with macular dystrophies.
      Our observations highlight the viability of objective, non-invasive evaluation of
      visual pigment in the healthy and diseased human retina by means of confocal
      fundus autofluorescence.

PMID- 18096157
TI  - Expression and cellular localization of prolactin and the prolactin receptor in
      mammalian retina.
AB  - Prolactin (PRL), originally associated with milk secretion, is known to have a
      wide variety of biological actions and diverse sites of production beyond the
      pituitary gland. Recent studies have demonstrated that PRL is synthesized in
      retinal tissue. To gain insights into the functional role of PRL in the mammalian
      retina, we mapped the distribution of the PRL protein and the expression and
      localization of the PRL receptor (PRLR) in the retina of adult rats and green
      monkeys. PRL was examined in retinal sections by double immunolabeling combining
      anti-PRL antibodies with antibodies specific for glutamine synthetase (labeling
      Muller cells), glial fibrillary acidic protein (labeling astrocytes), or neuronal
      nuclei protein (labeling neurons). PRL was detected throughout the rat retina: in
      the photoreceptor outer segments, Muller cells, interneurons, ganglion cells, and
      astrocytes. The PRLR was examined by RT-PCR, in situ hybridization,
      immunohistochemistry, and Western blot. The long isoform of the PRLR was
      localized in the photoreceptor nuclear layer, inner nuclear layer, and ganglion
      cell layer of rat retina. The monkey retina showed a similar distribution of PRL
      and PRLR immunoreactivities. These findings suggest that PRL functions as a local
      regulator of various cell types in the mammalian retina.

PMID- 18096159
TI  - Convergence of nociceptive information in the forebrain of female rats:
      reproductive organ response variations with stage of estrus.
AB  - Neurons in the preoptic area (POA) of the hypothalamus and the bed nucleus of
      stria terminalis (BST) play an important role in the neuroendocrine control of
      the reproductive cycle, mating behaviors and nociception. Single unit
      extracellular recordings were performed in the POA and BST region of 20 urethane
      anesthetized female rats during either the proestrus (elevated levels of
      estrogen/progesterone) or metestrus (low circulating hormones) stage of the
      estrous cycle. A total of 118 neurons in the POA and 65 neurons in the BST
      responded to the search stimuli, bilateral electrical stimulation of the
      viscerocutaneous branch of the pelvic nerve and/or sensory branch of the pudendal
      nerve (i.e., dorsal nerve of clitoris). Most of the neurons responding to the
      electrical search stimuli received a high degree of somatovisceral convergence,
      including inputs from the abdominal branches of the vagus, cervix, vagina, colon
      and skin territories on the perineum and trunk. Mean neuronal response thresholds
      for vaginal and cervical stimulation but not colon distention were significantly
      higher for animals tested during proestrus. Also, there was a shift in POA and
      BST neuronal responsiveness towards more inhibition and less excitation during
      proestrus for a variety of somatovisceral inputs. These data demonstrate that the
      changes in hormonal status affect the properties of POA and BST neurons, which
      likely relates not only to the functional importance of these inputs for
      reproductive behaviors but also for nociceptive processing as well.

PMID- 18096160
TI  - The antidepressant sertraline improves the phenotype, promotes neurogenesis and
      increases BDNF levels in the R6/2 Huntington's disease mouse model.
AB  - Huntington's disease (HD) is an inherited progressive neurodegenerative disorder
      characterized by progressive movement, psychiatric and cognitive disturbances.
      Previous studies have indicated that HD pathogenesis may be mediated in part by
      loss of brain derived neurotrophic factor (BDNF). Antidepressants selectively
      blocking serotonin reuptake can increase BDNF levels, and also may increase
      neurogenesis. Here we report that an SSRI antidepressant, sertraline, prolongs
      survival, improves motor performance, and ameliorates brain atrophy in the R6/2
      HD mouse model. Six-week-old R6/2 mice and nontransgenic control mice were
      administered either sertraline or vehicle daily. Motor function was assessed in
      an accelerating rotarod test and evaluated at 10 weeks. R6/2 mice exhibited
      reduced time on the rod. Sertraline treatment improved the motor performance in
      R6/2 mice, but did not affect nontransgenic mice. R6/2 mice showed significant
      striatal atrophy which was reduced by sertraline treatment. These beneficial
      effects of sertraline are associated with enhanced neurogenesis and increased
      BDNF levels in brain treated with sertraline. The effective serum and brain
      levels of sertraline are comparable to the levels achieved in human
      antidepressant treatment. Our findings provide evidence that sertraline is
      neuroprotective in this HD model. Successful treatment with sertraline in
      depressed HD patients has been reported; moreover, sertraline is safe and well
      tolerated for long-term administration, including in HD patients. Our findings
      suggest that a clinical trial of SSRI treatment in order to retard disease
      progression in human HD may be warranted.

PMID- 18096162
TI  - Epileptic seizures and hippocampal damage after cuprizone-induced demyelination
      in C57BL/6 mice.
AB  - Epileptic seizures are known to occur in different animal models of demyelination
      and have also been described in demyelinating diseases of the central nervous
      system (CNS) such as multiple sclerosis. How myelin deficiency might cause
      seizures is unknown, but may involve axonal pathology and resultant alterations
      in neuronal excitability. The cause of seizures occurring in rodent demyelination
      models is unknown. In the present study, we used EEG/video monitoring to record
      seizures occurring during chronic demyelination of C57BL/6 mice fed for 12 weeks
      with 0.2% cuprizone. Furthermore, in the search for a morphological correlate of
      the seizures, the hippocampal formation was examined histologically. Epileptiform
      spikes resembling interictal spikes known from chronic epilepsy were recorded in
      all cuprizone-treated mice, but not in controls. Most cuprizone-treated animals
      exhibited generalized tonic-clonic seizures upon stress-inducing stimuli. In
      addition to the known demyelination of the corpus callosum, massive demyelination
      was found in the hippocampal formation. This was associated with neuronal
      alterations, including a loss of neurons in the hilus of the dentate gyrus. In
      view of the role of the dentate gyrus in epileptogenesis, demyelination leading
      to axonal pathology and thus neuronal damage as observed in the hilus may be
      causally involved in the paroxysmal alterations observed after prolonged
      treatment with cuprizone. The present data suggest a potential role of the
      hippocampal formation for seizures occurring as a consequence of neuronal damage
      secondary to CNS demyelination.

PMID- 18096163
TI  - Long-term behavioral and neuroendocrine alterations following chronic social
      stress in mice: implications for stress-related disorders.
AB  - The period of adolescence is characterized by a high vulnerability to stress and
      trauma, which might result in long-lasting consequences and an increased risk to
      develop psychiatric disorders. Using a recently developed mouse model for chronic
      social stress during adolescence, we studied persistent neuroendocrine and
      behavioral effects of chronic social stress obtained 12 months after cessation of
      the stressor. As a reference, we investigated immediate effects of chronic stress
      exposure obtained at the end of the chronic stress period. Immediately after the
      7 week chronic stress period stressed animals show significantly increased
      adrenal weights, decreased thymus weight, increased basal corticosterone
      secretion and a flattened circadian rhythm. Furthermore, stressed animals display
      an increased anxiety-like behavior in the elevated plus maze and the novelty
      induced suppression of feeding test. Hippocampal mineralocorticoid receptor (MR)
      and the glucocorticoid receptor (GR) mRNA levels were significantly decreased. To
      investigate persistent consequences of this early stressful experience, the same
      parameters were assessed in aged mice 12 months after the cessation of the
      stressor. Interestingly, we still found differences between formerly stressed and
      control mice in important stress-related parameters. MR expression levels were
      significantly lower in stressed animals, suggesting lasting, possibly epigenetic
      alterations in gene expression regulation. Furthermore, we observed long-term
      behavioral alterations in animals stressed during adolescence. Thus, we could
      demonstrate that chronic stress exposure during a crucial developmental time
      period results in long-term, persistent effects on physiological and behavioral
      parameters throughout life, which may contribute to an enhanced vulnerability to
      stress-induced diseases.

PMID- 18096161
TI  - Postpubertal decrease in hippocampal dendritic spines of female rats.
AB  - Hippocampal dendritic spine and synapse numbers in female rats vary across the
      estrous cycle and following experimental manipulation of hormone levels in
      adulthood. Based on behavioral studies demonstrating that learning patterns are
      altered following puberty, we hypothesized that dendritic spine number in rat
      hippocampal CA1 region would change postpubertally. Female Sprague-Dawley rats
      were divided into prepubertal (postnatal day (P) 22), peripubertal (P35) and
      postpubertal (P49) groups, with the progression of puberty evaluated by vaginal
      opening, and estrous cyclicity subsequently assessed by daily vaginal smears.
      Spinophilin immunoreactivity in dendritic spines was used as an index of
      spinogenesis in area CA1 stratum radiatum (CA1sr) of hippocampus. First, electron
      microscopy analyses confirmed the presence of spinophilin specifically in
      dendritic spines of CA1sr, supporting spinophilin as a reliable marker of
      hippocampal spines in young female rats. Second, stereologic analysis was
      performed to assess the total number of spinophilin-immunoreactive puncta (i.e.
      spines) and CA1sr volume in developing rats. Our results indicated that the
      number of spinophilin-immunoreactive spines in CA1sr was decreased 46% in the
      postpubertal group compared to the two younger groups, whereas the volume of the
      hippocampus underwent an overall increase during this same developmental time
      frame. Third, to determine a potential role of estradiol in this process, an
      additional group of rats was ovariectomized (OVX) prepubertally at P22, then
      treated with estradiol or vehicle at P35, and spinophilin quantified as above in
      rats perfused on P49. No difference in spinophilin puncta number was found in OVX
      rats between the two hormone groups, suggesting that this developmental decrease
      is independent of peripheral estradiol. These changes in spine density coincident
      with puberty may be related to altered hippocampal plasticity and synaptic
      consolidation at this phase of maturity.

PMID- 18096164
TI  - Fecundity of Cryptosporidium parvum is correlated with intracellular levels of
      the viral symbiont CPV.
AB  - Differences in the virulence and fecundity of Cryptosporidium parvum isolates
      have been observed by several researchers studying cryptosporidiosis. The purpose
      of the present study was to determine if there was a correlation between
      intracellular levels of the viral symbiont CPV in C. parvum and fecundity of two
      isolates of the parasite, namely C. parvum Beltsville (B) and C. parvum Iowa (I).
      Dairy calves infected with 10(6)C. parvum-B excreted 5-fold more oocysts compared
      with calves infected with the same number of C. parvum-I oocysts. The increased
      fecundity of the former strain was corroborated by semi-quantitative PCR assay of
      DNA isolated from cell cultures infected with either C. parvum-B or C. parvum-I.
      Quantitative reverse transcriptase-PCR analysis of viral RNA revealed a 3-fold
      greater number of CPV in C. parvum-B compared with C. parvum-I oocysts. These
      findings may indicate a role for CPV in fecundity and possibly virulence of C.
      parvum.

PMID- 18096165
TI  - Over-expression of angiotensin II type 2 receptor (agtr2) reduces atherogenesis
      and modulates LOX-1, endothelial nitric oxide synthase and heme-oxygenase-1
      expression.
AB  - Atherogenesis is associated with inflammation and oxidative stress. Activation of
      renin-angiotensin system with generation of angiotensin II and type 1 receptor
      (AT1R) stimulation has been amply reported in atherosclerosis. Since angiotensin
      II type 2 receptor (AT2R) activity is purported to oppose the effects of AT1R, we
      hypothesized that AT2R (agtr2) over-expression would inhibit atherogenesis. We
      prepared recombinant adeno-associated virus type-2 (AAV) carrying AT2R cDNA
      (AAV/AT2R), and homozygous LDLR-deficient (KO) mice were given AAV/AT2R, AAV/Neo
      or saline. All mice were placed on a high cholesterol diet. After 18 weeks, AT2R
      was found to be over-expressed systemically in AAV/AT2R-treated mice.
      Atherogenesis in aorta was reduced in the AAV/AT2R group by approximately 50%
      compared to other LDLR KO mice groups. Expression of NADPH oxidase, nitrotyrosine
      and NF-kappaB was increased in aortic tissues of the LDLR KO mice given saline or
      AAV/Neo, but not in mice with AT2R upregulation. Expression of endothelial nitric
      oxide synthase (eNOS) and heme-oxygenase-1 (HO-1) was decreased and that of the
      lectin-like oxidized-LDL receptor (LOX-1) increased in the LDLR KO mice, but not
      in the mice with AT2R over-expression. Further, Akt-1 phosphorylation was reduced
      in the LDLR KO mice, but not in the mice with AT2R over-expression. Thus, AT2R
      upregulation can reduce atherogenesis, possibly by modulating oxidative stress
      and the pro-inflammatory cascade, mediated via Akt-1. Over-expression of AT2R may
      be an important therapeutic approach in atherosclerosis.

PMID- 18096166
TI  - Paraoxonase (PON1) is associated with familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCH) is a common genetic lipid disorder of
      which the molecular basis still remains to be elucidated. Since the HDL
      associated enzyme serum paraoxonase (PON1) is associated with variation in serum
      lipids and lipoproteins, we determined whether variation in PON1 also contributes
      to the FCH phenotype. The study population consisted of 32 well-defined families
      with FCH, including 103 FCH patients and 240 normolipidemic relatives (NLR). In
      addition to plasma lipids and lipoproteins we determined PON1 activity
      (arylesterase- and paraoxonase activity) as well as the common genetic variants 
      107C>T, 55L>M and 192Q>R in the PON1 gene. The arylesterase activity was
      significantly higher in FCH patients when compared to NLR (P<0.001). In the total
      population, the PON1 genetic variants associated with the highest arylesterase
      activity (-107CC and 55LL) also associated with higher levels of total
      cholesterol, apolipoprotein B, triglycerides and VLDL-cholesterol and decreased
      levels of HDL-cholesterol. In support, the combination of the -107CC with the
      55LL genotype associated with a significant increased risk for FCH when compared
      to the -107TT/55MM genotype (odds ratio 5.0 (95% CI, 1.3-19.1, P=0.02)). In
      conclusion, in this population of subjects from well-defined families with FCH,
      PON1 is biochemically and genetically associated with FCH.

PMID- 18096168
TI  - The relationship between the metabolic syndrome defined by various criteria and
      the extent of coronary artery disease.
AB  - The association between the severity of coronary artery disease (CAD) and
      metabolic syndrome (MS) as defined by recently proposed criteria remains unknown.
      Therefore, we investigated the association between the severity of CAD and MS
      based on four sets of criteria. The frequency of MS and the severity of CAD
      determined using the Gensini score (GS) were assessed in 656 consecutive patients
      who underwent elective coronary angiography for the first time. Using the various
      criteria, 25.4% of males and 25.6% of females fulfilled the NCEP-ATPIII criteria,
      46.6% of males and 21.3% of females fulfilled the International Diabetes
      Federation (IDF) criteria, 44.0% of males and 41.9% of females fulfilled the
      American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI)
      criteria, and 42.5% of males and 18.8% of females fulfilled the Japanese
      definition. On multivariate analysis, MS defined according to the AHA/NHLBI
      criteria was related to an increased risk of extensive CAD in males [odds ratio
      (OR) 1.89, p=0.001]. MS defined according to the IDF criteria was associated with
      the highest risk for extensive CAD in females (OR 2.83, p=0.019). In conclusion,
      MS was found to be associated with the extent of CAD. However, gender-specific
      differences and MS definition-specific differences exist.

PMID- 18096167
TI  - Alterations in cell adhesion molecules and other biomarkers of cardiovascular
      disease in patients with metabolic syndrome.
AB  - Metabolic syndrome is considered a hyperinsulinemic and inflammatory state
      closely associated to endothelial dysfunction causing an increased incidence of
      ischemic cardiovascular events and high mortality. The main objective of the
      present study was to determine whether leukocitary and soluble cell adhesion
      molecules were altered in patients with metabolic syndrome in comparison with
      control subjects. Cell adhesion molecules, mainly of leukocitary location, have
      been not previously evaluated in specifically designed cross-sectional studies
      involving male patients with metabolic syndrome. Moreover, other circulating
      markers of different candidate atherogenic risk parameters were also studied and
      the potential existence of a progressive relation between the number of metabolic
      syndrome components and the above mentioned biomarkers was analyzed. Thirty one
      male patients with metabolic syndrome (ATPIII definition) and 56 male control
      subjects were studied. We evaluated different markers of insulin resistance,
      inflammation and atherosclerosis, as well as protective factors. Patients with
      metabolic syndrome showed (a) hypoadiponectinemia (4551 +/- 2302 ng/ml vs. 5865
      +/- 2548 ng/ml, respectively; p<0.05), (b) an atherogenic lipid and lipoprotein
      profile, (c) altered HDL chemical composition accompanied by higher cholesteryl
      ester-triglyceride interchange carried out by CETP, (d) diminished Lp-PLA(2)
      activity (6.5 +/- 1.9 vs. 7.3 +/- 2.2, p<0.05, respectively), antioxidant enzyme
      related with LDL oxidation, which was positively associated with QUICKI and
      negatively with VCAM-1 and lymphocyte CD18, and (e) high soluble (VCAM-1: 17 +/-5
      vs. 13 +/- 4 ng/ml, respectively; p<0.0005) and leukocyte adhesion molecule
      expression (monocyte CD54: 52 +/- 15 vs. 45 +/-12 arbitrary units, respectively;
      p<0.0005; and lymphocyte CD49d: 312 +/- 56 vs. 284 +/- 64 arbitrary units,
      respectively; p < 0.05). The increment in leukocyte and soluble cell adhesion
      molecules, crucial for leukocyte interaction with the endothelium and migration
      into the artery wall, in combination with the other disorders described above
      reinforce the presence of a clinical status with high propensity to type 2
      diabetes and atherosclerotic cardiovascular disease.

PMID- 18096169
TI  - The CCR2 promoter polymorphism T-960A, but not the serum MCP-1 level, is
      associated with endothelial function in prediabetic individuals.
AB  - Monocyte-chemoattractant-protein (MCP)-1 and its receptor CCR2 have been shown to
      play a pivotal role in vascular inflammation and atherosclerotic plaque
      formation. However, it is currently unclear whether MCP-1/CCR2 triggered
      inflammation affects nitric oxide (NO)-bioavailability, hence influencing
      vascular function, a sign of early atherosclerosis. Therefore, we sought to
      investigate the association between serum levels of MCP-1 and NO-bioavailability,
      expressed as flow mediated dilation (FMD) in vivo, and the impact of CCR2 gene
      variations on FMD. We studied a German population of 242 prediabetic individuals
      (144 women, 98 men; mean age 45+/-0.8 years) via FMD by high-resolution
      ultrasound (13MHz). In order to replicate our findings, a second, independent
      population (n=115; 44 women, 77 men; mean age 48+/-1.0 years) (total=357
      individuals) from Italy was studied. Vascular function in the Italian population
      was studied via intra-arterial application of acetylcholine. MCP-1 serum-levels
      were assessed by ELISA and CCR2 polymorphisms were determined by sequencing. MCP
      1 serum levels showed no association with FMD (p=0.90), whereas the CCR2 promoter
      polymorphism was associated with elevated FMD (T/T: 5.6+/-0.3%; T/A: 6.7+/-0.4%;
      A/A: 8.3+/-0.8%; p=0.01) after adjusting for possible confounders. These results
      were confirmed in the independent Italian population (A/A: 97.1+/-20.3 vs. T/T:
      60.5+/-5.6% forearm blood-flow increase; p<0.05). When testing for the functional
      relevance of the T-960A (rs3918359) polymorphism, we found that the A/A-genotype
      was associated with moderately increased protein binding in EMSA, increased
      promoter activity in luciferase assays and reduced transendothelial monocyte
      migration. In conclusion, MCP-1 serum levels do not reflect endothelial function
      in vivo in prediabetic individuals. However, the functionally relevant CCR2
      promoter polymorphism T-960A (rs3918359) is associated with elevated vascular
      function. This might be due to reduced subendothelial inflammation, mediated by
      reduced transendothelial monocyte-migration ability.

PMID- 18096170
TI  - Development of an RSA calibration system with improved accuracy and precision.
AB  - In this study, a new radiostereometric analysis (RSA) calibration cage was
      developed with the aim of improving the accuracy and precision of RSA. This
      development consisted of three steps: a numerical simulation technique was first
      used to design the new cage; a synthetic imaging method was then implemented to
      predict the performance of the designed cage before it was actually fabricated;
      and an experimental phantom test was finally conducted to verify the actual
      performance of the new cage and compare with two currently widely used cages.
      Accuracy was calculated as the 95% prediction intervals from regression analyses
      between the measured and actual displacements, and precision was defined as the
      standard deviation of repeated measurements. The final experimental phantom tests
      showed that the accuracy and precision of the new calibration cage were improved
      by about 40% over an existing biplanar cage and by about 70% compared to a
      uniplanar cage design. This new cage can be used with any skeletal joints, in
      either static or kinematic examination, which is helpful for the standardization
      of the RSA application.

PMID- 18096171
TI  - Development of a method for the determination of UV filters in water samples
      using stir bar sorptive extraction and thermal desorption-gas chromatography-mass
      spectrometry.
AB  - Stir bar sorptive extraction (SBSE) in combination with thermal desorption-gas
      chromatography-mass spectrometry (TD-GC-MS) was applied for the determination of
      9 UV filters in water samples. The stir bar coated with polydimethylsiloxane
      (PDMS) was added to 20 mL of water sample at pH 2 (10% MeOH) and stirred at 1000
      rpm for 180 min. Then, the stir bar was subjected to TD-GC-MS. The desorption
      conditions (desorption temperature and desorption time) and SBSE parameters
      (ionic strength, pH, presence of organic solvent and time) were optimised using a
      full factorial design and a Box-Behnken design, respectively. The method shows
      good linearity (correlation coefficients >0.994) and reproducibility (RSD<16%).
      The extraction efficiencies were above 63% for all the compounds. Detection
      limits were between 0.2 and 63 ng/L. The developed method offers the ability to
      detect several UV filters at ultra-low concentration levels with only 20 mL of
      sample volume. The effectiveness of the method was tested by analysing real
      samples such as lake water, river water and treated wastewater. The application
      of the method allowed reporting the levels of UV filters in environmental water
      samples.

PMID- 18096172
TI  - Reversed-phase liquid chromatography-mass spectrometry of site-specific chemical
      modifications in intact immunoglobulin molecules and their fragments.
AB  - The employment of a diphenyl column for the separation of intact monoclonal
      antibodies (mAbs) and their fragments by reversed-phase HPLC is discussed as a
      novel approach for the characterization of chemical modifications in a site
      specific manner. Chromatographic separation of the intact mAb07 on the diphenyl
      support resulted in the separation of the cysteinylated from the non
      cysteinylated mAb. A detected mass increase of 119 Da by mass spectrometric
      sequence analysis confirmed the cysteinylation. Furthermore, the diphenyl column
      resolved site-specific oxidation of five different methionine residues in the
      heavy chain (HC) of mAb03. Oxidized mAb03 HC eluted as five distinct peaks with
      shorter retention times than the corresponding peak representing unoxidized HC.
      Analysis of these peaks by in-line mass spectrometric analysis confirmed the site
      specific oxidation of five different methionine residues. In another application,
      the diphenyl column was able to resolve free sulfhydryl groups containing Fc and
      Fab fragments, which were generated by limited proteolysis with endoproteinase
      Lys-C. The free sulfhydryl groups were responsible for a mass shift of
      approximately 2 Da. Their identity was further confirmed by N-ethylmaleimide
      labeling, which caused a shift in their chromatographic retention and led to a
      mass increase of 250 Da. This is the first report about chromatographic
      resolution on a reversed-phase column that results in site-specific separation of
      chemical modifications in intact mAb and mAb fragments.

PMID- 18096173
TI  - Fabrication and performance of poly(methyl methacrylate) microfluidic chips with
      fiber cores.
AB  - In this work, a piece of glass fiber was inserted into the channel of a
      poly(methyl methacrylate) (PMMA) electrophoresis microchip to enhance the
      electroosmotic flow (EOF) and the separation efficiency. The EOF value of the
      glass fiber-containing microchannel at pH 8.2 was determined to be 4.17 x 10(
      4)cm2 V(-1)s(-1). The performance of the new microchip was demonstrated by its
      ability to separate and detect three purines coupled with end-column amperometric
      detection. In addition, a piece of trypsin-immobilized glass fiber was inserted
      into the channel of a PMMA microchip to fabricate a core-changeable microfluidic
      bioreactor that can be regenerated by changing the fiber. The in-channel fiber
      bioreactor has been coupled with matrix-assisted laser desorption ionization time
      of-flight mass spectrometry for the digestion and peptide mapping of bovine serum
      albumin and myoglobin.

PMID- 18096174
TI  - Comparison of gas chromatography-ion-trap tandem mass spectrometry systems for
      the determination of polychlorinated dibenzo-p-dioxins, dibenzofurans and dioxin
      like polychlorinated biphenyls.
AB  - Two gas chromatography-mass spectrometry systems equipped with an ion-trap mass
      analyzer working in tandem mode (GC-MS-MS) were evaluated for the determination
      of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like
      polychlorinated biphenyls (PCBs) in food samples. The performance of the two ion
      trap instruments, which dispose of an external ion source (ThermoFinnigan
      GCQ/Polaris) and internal ionization (Varian Saturn 2,200), have been compared in
      terms of linearity, repeatability, limit of detection and long-term precision.
      Both instruments provided similar run-to-run and day-to-day precisions, ranging
      from 2% to 8% and between 2% and 13%, and instrumental limits of detection
      between 0.09 and 0.36 pg injected for PCDD/Fs and from 0.03 to 0.09 pg injected
      for dioxin-like PCBs. Although both instruments seem to be suitable for food
      analysis, only the use of external ionization allowed to achieve reliable results
      for PCDD/F determination at concentrations close to the maximum residue levels
      established by the EU for foods. Internal ionization provides high limits of
      detection (from 10- to 30-fold higher) and worse precision (RSD, 14-43%). In
      contrast, for dioxin-like PCBs both instruments allowed to obtain excellent
      results with precisions lower than 15%.

PMID- 18096175
TI  - Liquid chromatography and ultra-performance liquid chromatography-mass
      spectrometry fingerprinting of human urine: sample stability under different
      handling and storage conditions for metabonomics studies.
AB  - Typically following collection biological samples are kept in a freezer for
      periods ranging from a few days to several months before analysis. Experience has
      shown that in LC-MS-based metabonomics research the best analytical practice is
      to store samples as these are collected, complete the sample set and analyse it
      in a single run. However, this approach is prudent only if the samples stored in
      the refrigerator or in the freezer are stable. Another important issue is the
      stability of the samples following the freeze-thaw process. To investigate these
      matters urine samples were collected from 6 male volunteers and analysed by LC-MS
      and ultra-performance liquid chromatography (UPLC)-MS [in both positive and
      negative electrospray ionization (ESI)] on the day of collection or at intervals
      of up to 6 months storage at -20 degrees C and -80 degrees C. Other sets of these
      samples underwent a series of up to nine freeze-thaw cycles. The stability of
      samples kept at 4 degrees C in an autosampler for up to 6 days was also assessed,
      with clear differences appearing after 48h. Data was analysed using multivariate
      statistical analysis (principal component analysis). The results show that sample
      storage at both -20 and -80 degrees C appeared to ensure sample stability.
      Similarly up to nine freeze thaw cycles were without any apparent effect on the
      profile.

PMID- 18096176
TI  - Optimisation of wort volatile analysis by headspace solid-phase microextraction
      in combination with gas chromatography and mass spectrometry.
AB  - The aim of this study was to create a simple, solventless technique without
      derivatisation in order to analyze a broad range of volatiles in beer wort. A
      method was developed using headspace solid-phase microextraction coupled with gas
      chromatography and mass spectrometry. The procedure was optimised by selection of
      the appropriate fibre and optimisation of extraction temperature, extraction
      time, and salting-out. The detection limits were well below the actual wort
      concentrations of the selected volatiles, ranging from 12 ng/l for linalool to
      0.53 microg/l for furfural. Moreover, the procedure showed a good linearity and
      was applied to the analysis of wort samples taken from a wort boiling process in
      an industrial brewery.

PMID- 18096177
TI  - Development of a pressurized liquid extraction-solid-phase extraction followed by
      liquid chromatography-electrospray ionization tandem mass spectrometry method for
      the quantitative determination of benzoxazolinones and their degradation products
      in agricultural soil.
AB  - A new analytical method for the quantitative determination of benzoxazolinones
      and their degradation products in agricultural soils based on the use of
      pressurized liquid extraction (PLE) followed by solid-phase extraction (SPE) and
      then instrumental determination using liquid chromatography-electrospray
      ionization tandem mass spectrometry (LC-ESI-MS-MS) is described. Using this
      method, the characterization, separation and quantitative detection of a mixture
      of two benzoxazolinones, benzoxazolin-2-one (BOA) and 6-methoxybenzoxazolin-2-one
      (MBOA) and their degradation products, 2-aminophenol (APH), N-(2
      hydroxyphenyl)malonamic acid (HMPMA), 2-amino-3-H-phenoxazin-3-one (APO), 9
      methoxy-2-amino-3-H-phenoxazin-3-one (AMPO), 2-acetylamino-3-H-phenoxazin-3-one
      (AAPO) and 2-acetylamino-9-methoxy-2-amino-3-H-phenoxazin-3-one (AAMPO) was
      achieved. The complete LC-ESI-MS-MS precursor-product ion fragmentation pathways
      for the degradation products of benzoxazolinones are described for the first
      time. Quantitative analysis was done in the multiple reaction mode using two
      specific combinations of precursor-product ion transitions for each compound. The
      optimized method was quality assessed by the measure of parameter as recovery,
      linearity, sensitivity, repeatability and reproducibility. Recoveries of the
      analytes ranged from 53 to 123%. The developed method offered improvements to the
      sensitivity as compared with our previously LC-MS method, with detection limits
      down to 2.4-21 ng/g of dry weight. This achievement allows us to identify and
      quantify for the first time degradation products of benzoxazolinones in real
      agricultural soil samples. Analytes were found in the range of 20.6-149 ng/g dry
      weight.

PMID- 18096178
TI  - New chiral and restricted-access materials containing glycopeptides as selectors
      for the high-performance liquid chromatographic determination of chiral drugs in
      biological matrices.
AB  - Two new chiral and restricted-access materials containing glycopeptide
      antibiotics as chiral selectors (chiro-Glyco-RAM) were designed, suitable for the
      direct HPLC injection of biological fluids containing chiral drugs without any
      sample pre-treatment or pre-columns coupling. The external surface of the porous
      silica support was covered with a bio-compatible hydrophilic polymeric network
      (polyvinyl alcohol, PVA) while the chiral phase based on either teicoplanin (TE)
      or teicoplanin aglycone (TAG) was exclusively confined to the internal region.
      The chiro-Glyco-RAM supports were synthesized by the following steps: (a)
      introduction of 3-aminopropyl groups on 100 A pore size silica gel; (b)
      activation of the aminopropylated silica with 1,6-diisocyanatohexane; (c)
      functionalization of the external region of the porous silica with PVA; (d)
      covalent linking of TE/TAG to the internal surface. The average pore diameter of
      the chiro-Glyco-RAM supports, calculated by inverse size-exclusion chromatography
      (ISEC), was about 80 A and able to exclude macromolecules heavier than about
      20,000 Da (such as the most abundant serum proteins) from the pores. The recovery
      of bovine serum albumin (BSA) was almost quantitative. HPLC analyses of model
      chiral drugs were performed using hydro-organic mobile phases consisting of an
      organic solvent (acetonitrile or methanol) and aqueous solutions of ammonium
      acetate (0.020 M) or ammonium formate (0.0025-0.0050 M).

PMID- 18096179
TI  - Control of particle cluster dispersion using responsive polymeric additives.
AB  - The dispersion behavior of clusters of hydrophilic and hydrophobic silica treated
      with a thermoresponsive polymer has been investigated. The influence of the
      thermoresponsive interfacial chemistry was assessed by performing dispersion
      studies in poly(dimethylsiloxane) (PDMS) at 25 and 68 degrees C for agglomerates
      of powders incorporating poly(N-isopropyl acrylamide) (PNIPAM), a
      thermoresponsive polymer, and water. While the dispersion of clusters of
      hydrophilic silica was found to be temperature independent, dispersion of
      hydrophobic silica exhibited a temperature dependency. The response of the
      polymer upon temperature variation brings about modifications in the
      interparticle interactions of the PNIPAM-treated powders thus leading to changes
      in the cluster cohesivity. The dependence of the cluster cohesivity on
      temperature was evidenced through changes in the dispersion mechanism and
      kinetics of the treated silica clusters at both tested temperatures. In addition,
      optical microscopy of silica suspensions with and without PNIPAM at 25 and 60
      degrees C, illustrated the effect of the polymer presence and configuration on
      the particle-particle interaction forces. While micrographs of the particles at
      25 degrees C show less evidence of particle aggregation, the micrographs at 60
      degrees C illustrate an increase in aggregation suggesting an enhancement in the
      attractive forces between particles.

PMID- 18096180
TI  - Determination of interfacial tension between two immiscible polymers with and
      without surfactants at the interface.
AB  - A second-order drop deformation method for inferring interfacial tension between
      two immiscible polymers is proposed and shown to improve the accuracy of tension
      estimate appreciably. A small step-strain method, which uses a strong flow
      (capillary number >1) and short flow time approximately O(0.1s), is successfully
      developed to avoid complications caused by the surfactants for surfactant-laden
      drops. This method is demonstrated to give good tension estimates for a range of
      viscosity ratios and surface coverage.

PMID- 18096181
TI  - Translational motion of a spherical particle near a planar liquid-fluid
      interface.
AB  - The translational electrophoretic motion of a colloidal spherical particle
      parallel to a planar liquid-fluid interface is analyzed by using the reciprocal
      theorem developed by Yariv and Brenner [E. Yariv, H. Brenner, J. Fluid Mech. 484
      (2003) 85]. Based on the thin electric double layers assumption, analytical
      solutions of the forces acting on the particle are obtained, and the influence of
      the liquid-fluid interface on the electrophoretic velocity of the particle is
      studied. It is found that the speed of the particle's electrokinetic motion will
      increase as the separation distance between the particle and the interface
      decreases. This enhancement of electrophoretic mobility becomes more significant
      when the viscosity of the fluid phase becomes larger.

PMID- 18096182
TI  - University students' perceptions of pre-school and kindergarten children who
      stutter.
AB  - To determine how early "the stuttering stereotype" is assigned, 160 university
      students rated a hypothetical vignette depicting either a 3-, 4-, 5-, or 6-year
      old with or without the statement "He stutters". A factor analysis of the
      semantic differential scale showed a three-factor solution comprised of 17 of the
      25 bi-polar adjective pairs. The factor labeled personality showed significantly
      more negative ratings for 2-, 4-, 5-, or 6-year-old children based on the
      inclusion of the "He stutters" sentence. There were no differences between male
      and female raters. A significant difference was found between raters who were
      knew someone who stuttered and raters who did not know someone who stuttered on
      the personality factor. Raters who were knew someone who stuttered were
      significantly more likely to assign more positive ratings to the children.
      LEARNING OUTCOMES: Readers should be able to learn and understand: (1) the
      research describing the negative stereotypes associated with stuttering; (2) the
      vignette method used to evaluate stereotypes in children and youth; (3) the
      negative perceptions of the sentence "He stutters" on raters' perception of
      personality, sociability and speech for children as young as 3-, 4-, 5-, or 6
      year-olds; and (4) the familiarity with a person who stutters and raters'
      perceptions of children who stutter.

PMID- 18096183
TI  - Selection of anti-cancer antibodies from combinatorial libraries by whole-cell
      panning and stringent subtraction with human blood cells.
AB  - Traditional strategies for the identification of cell-surface cancer targets
      often fall short of their objective. For example, whole-cell panning of antibody
      libraries to isolate a diverse panel of antibodies directed against targets on
      cancer cells often identifies all immunogenic and/or abundant cell-surface
      antigens, not simply tumor-specific or tumor-associated antigens. Here we
      describe the use of stringent negative selection in combination with positive
      panning to increase tumor specificity and clinical relevance of selected
      antibodies. Sera from cancer cell-immunized mice showed strong binding to
      immunizing cancer cell lines but also cross-reacted strongly with human blood
      cells. Antisera blood cell binding was considerably decreased after stringent
      subtraction with human red blood cells (RBCs) and white blood cells (WBCs), yet
      cancer cell specificity was retained. In order to select for a higher percentage
      of clinically relevant antibodies for potential therapeutic use, stringent
      negative selection by RBC subtraction was employed in whole-cell panning of a
      disease-specific phage displayed antibody library on the prostate cancer cell
      line, PC-3. Isolated antibodies were found to bind to target antigens implicated
      in tumorigenicity and cancer cell migration and/or invasion, and included CD26,
      CDCP1, and the integrin complexes alpha2/beta1, alpha3/beta1, alpha5/beta1, and
      alpha6/beta4. Compared with traditional cell panning, this method considerably
      increased the selectivity of antibodies to tumor-associated antigens.

PMID- 18096184
TI  - Cold activity of Beauveria and Metarhizium, and thermotolerance of Beauveria.
AB  - Heat and cold are environmental abiotic factors that restrict the use of
      entomopathogenic fungi as agents for biological control of insects. The
      thermotolerance and cold activity of 60 entomopathogenic fungal isolates,
      including five species of Beauveria and one isolate of Engyodontium albus
      (=Beauveria alba) were examined as to tolerance of temperatures that might be
      encountered during field use. In addition, cold activity of eight Metarhizium
      spp. isolates was evaluated. The isolates were from various geographic regions,
      arthropod hosts or substrates. High variability in conidial thermotolerance was
      found among the Beauveria spp. isolates after exposure to 45 degrees C for 2 h,
      as evidenced by low (0-20%), medium (20-60%), or high germination (60-80%). The
      thermal death point (0% germination) for three rather thermotolerant B. bassiana
      isolates (CG 138, GHA and ARSEF 252) was 46 degrees C for 6 h. At low
      temperatures (5 degrees C), with few exceptions (e.g. CG 66, UFPE 479, CG 227, CG
      02), most of the B. bassiana isolates germinated well (ca. 100%). On the other
      hand, only one isolate of Metarhizium sp. was cold-active (i.e. ARSEF 4343 from
      Macquarie Island, 54.4 degrees S, Australia). This probably is a M. frigidum
      isolate. The E. albus isolate (UFPE 3138) was the most susceptible isolate to
      both heat and cold stress. Isolates ARSEF 252 and GHA of B. bassiana, on the
      other hand, presented exceptionally high thermotolerance and cold activity. Some
      isolates with high cold activity, however, were thermosensitive (e.g. ARSEF 1682)
      and others with high thermotolerance had low cold activity (e.g. CG 227). An
      attempt to correlate the latitude of origin with thermotolerance or cold activity
      indicated that B. bassiana isolates from higher latitudes were more cold-active
      than isolates from nearer the equator, but there was not a similar correlation
      for heat.

PMID- 18096185
TI  - Effect of Acanthocephala infection on the reproductive potential of crustacean
      intermediate hosts.
AB  - The effect of a naturally acquired infection by three acanthocephalan parasites
      Dentitruncus truttae, Echinorhynchus truttae, and Polymorphus minutus on the
      reproductive potential of their intermediate host, Echinogammarus tibaldii
      (Amphipoda) from Lake Piediluco (Centre of Italy) was assessed. During May 2007,
      1135 amphipods were collected from two different samplings and examined for
      larval helminths. Forty-five amphipods were infected and of those, 16 were
      infected with D. truttae (intensity=1-3 larvae), 15 with E. truttae (intensity=1
      2 larvae), and 14 with P. minutus (intensity=1 larva). The sex ratio was nearly
      1:1 in all examined amphipods. One female infected with D. truttae contained six
      eggs in the brood pouch and another female infected with E. truttae contained
      five eggs. However, none of the eight female amphipods harbouring P. minutus
      larva contained eggs in their brood pouch. Uninfected females of the same size
      and body length as that of the infected females contained between 20 and 32 eggs.
      No acanthocephalan species were found to co-occur.

PMID- 18096187
TI  - Qualitative evidence of Ri specific IgG-synthesis in the cerebrospinal fluid from
      patients with paraneoplastic neurological syndromes.
AB  - The presence of Ri-specific oligoclonal IgG bands in the CSF was investigated in
      five patients with paraneoplastic anti-Ri associated neurological syndromes (PNS)
      and six controls. In 4/5 CSF samples reactivity of IgG bands with recombinant Ri
      antigen was found using isoelectrofocusing combined with affinity blotting; in
      one patient with absence of oligoclonal bands of total IgG in CSF Ri-specific
      oligoclonal bands were detected with the same sample, indicating a higher
      sensitivity of Ri-specific affinity blotting as compared to affinity blotting
      with anti-human IgG antibodies. Our results confirm previous studies
      demonstrating IgG synthesis against onconeuronal antigens by intrathecal B-cell
      clones in PNS and extend this observation to patients with anti-Ri syndrome. The
      pathogenic relevance of these antibodies, however, is further challenged by the
      finding that specific intrathecal IgG synthesis might not be a prerequisite of
      CNS involvement, because it was missed in one of our patients.

PMID- 18096188
TI  - Enlarged, multifocal upper limb neuropathy with HTLV-I associated myelopathy in a
      patient with chronic adult T-cell leukemia.
AB  - The authors herein describe a case of multifocal peripheral neuropathy with HTLV
      I-associated myelopathy (HAM) in a patient with chronic adult T-cell leukemia
      (ATL). The clinical features included subacute progressive sensory-motor
      neuropathy in the bilateral upper limbs, and bilateral pyramidal tract
      involvement with bladder dysfunction. An MRI with (67)gadolinium enhancement
      revealed enlargement of the affected peripheral nerves. (8)FDG positron emission
      tomography (PET) disclosed increased uptake in the affected nerves, suggesting
      neurolymphomatosis or inflammation. Anti-HTLV-I antibody was positive in both the
      serum and CSF. The HTLV-I proviral load in the peripheral blood mononuclear cells
      was high. Chemotherapy for ATL resulted in marked improvement of motor functions
      in the upper limbs. This is the first case of multifocal upper limb neuropathy
      with HAM in a patient with chronic ATL.

PMID- 18096186
TI  - Function of the C-terminal domain of the DEAD-box protein Mss116p analyzed in
      vivo and in vitro.
AB  - The DEAD-box proteins CYT-19 in Neurospora crassa and Mss116p in Saccharomyces
      cerevisiae are general RNA chaperones that function in splicing mitochondrial
      group I and group II introns and in translational activation. Both proteins
      consist of a conserved ATP-dependent RNA helicase core region linked to N and C
      terminal domains, the latter with a basic tail similar to many other DEAD-box
      proteins. In CYT-19, this basic tail was shown to contribute to non-specific RNA
      binding that helps tether the core helicase region to structured RNA substrates.
      Here, multiple sequence alignments and secondary structure predictions indicate
      that CYT-19 and Mss116p belong to distinct subgroups of DEAD-box proteins, whose
      C-terminal domains have a defining extended alpha-helical region preceding the
      basic tail. We find that mutations or C-terminal truncations in the predicted
      alpha-helical region of Mss116p strongly inhibit RNA-dependent ATPase activity,
      leading to loss of function in both translational activation and RNA splicing.
      These findings suggest that the alpha-helical region may stabilize and/or
      regulate the activity of the RNA helicase core. By contrast, a truncation that
      removes only the basic tail leaves high RNA-dependent ATPase activity and causes
      only a modest reduction in translation and RNA splicing efficiency in vivo and in
      vitro. Biochemical analysis shows that deletion of the basic tail leads to weaker
      non-specific binding of group I and group II intron RNAs, and surprisingly, also
      impairs RNA-unwinding at saturating protein concentrations and nucleotide
      dependent tight binding of single-stranded RNAs by the RNA helicase core.
      Together, our results indicate that the two sub-regions of Mss116p's C-terminal
      domain act in different ways to support and modulate activities of the core
      helicase region, whose RNA-unwinding activity is critical for both the
      translation and RNA splicing functions.

PMID- 18096189
TI  - Cardiovascular effects of transdermally delivered bupranolol in rabbits: effect
      of chemical penetration enhancers.
AB  - Bupranolol is a promising candidate for transdermal drug delivery system (TDDS)
      development. The effect of permeation enhancers on the in vivo delivery and beta
      blocking effect of reservoir type TDDS was studied in comparison with intravenous
      BPL in rabbits. The beta-blocking effect was quantified by measuring the
      inhibition of isoprenaline induced tachycardia in rabbits after BPL
      administration via transdermal and intravenous routes. The reservoir type TDDS
      containing a hydroxypropyl cellulose gel and polyethylene membrane was used as a
      control device. In comparison, the TDDS containing skin penetration enhancers,
      either 2-pyrrolidone or partially methylated beta cyclodextrin (PMbetaCD) were
      evaluated. The control device (no enhancer) produced about 52% inhibition of
      isoprenaline induced tachycardia at 2 h and the effect continued over 24 h
      application period, however, the devices with 2-pyrolidone or PMbetaCD produced
      about 85% inhibition of isoprenaline induced tachycardia at 3 h and the same
      effect continued over 24 h application period. Likewise, the AUC of these devices
      were significantly higher than that of control device. The intravenous bupranolol
      showed rapid decline in the pharmacodynamic effect with time indicating its rapid
      elimination. The in vivo delivery of bupranolol (as estimated by a mass balance
      study) from the devices made with pyrolidone or PMbetaCD was 3-fold higher than
      that of control. The results of this study strongly suggest that the penetration
      enhancers in the TDDS increased the in vivo delivery of BPL, thereby increased
      the beta-blocking activity of BPL by 50-60% higher than control, enabling the
      reduction of the TDDS patch size, accordingly.

PMID- 18096190
TI  - Incidence of marine debris and its relationships with benthic features in Gray's
      Reef National Marine Sanctuary, Southeast USA.
AB  - Gray's Reef National Marine Sanctuary (GRNMS) is an increasingly popular site for
      recreational fishing and diving in the South Atlantic Bight (SAB). As a result,
      there has been heightened concern about potential accumulation of marine debris
      and its consequent effects on sanctuary resources. Field surveys were conducted
      at GRNMS in 2004 and 2005 to provide a spatially comprehensive characterization
      of benthic communities and to quantify the distribution and abundance of marine
      debris in relation to bottom features. The spatial distribution of debris was
      concentrated in the center of the sanctuary and was most frequently associated
      with ledges rather than other bottom types. On ledges, the presence and abundance
      of debris was significantly related to observed boating activity and
      physiographic features including ledge height, ledge area, and percent cover of
      benthic organisms. The results from this study will aid managers in optimizing
      cleanup efforts and long-term monitoring of debris accumulation patterns at GRNMS
      and other hard bottom areas in the SAB.

PMID- 18096192
TI  - Movement interference in autism-spectrum disorder.
AB  - Movement interference occurs when concurrently observing and executing
      incompatible actions and is believed to be due to co-activation of conflicting
      populations of mirror neurons. It has also been suggested that mirror neurons
      contribute towards the imitation of observed actions. However, the exact neural
      substrate of imitation may depend on task demands: a processing route for goal
      directed meaningful actions may be distinct from one for non-goal-directed
      actions. A more controversial role proposed for these neurons is in theory of
      mind processing, along with the subsequent suggestion that impairment in the
      mirror neuron circuit can contribute to autism-spectrum disorder (ASD) where
      individuals have theory of mind deficits. We have therefore examined movement
      interference in nine ASD participants and nine matched controls while performing
      actions congruent and incongruent with observed meaningless arm movements. We
      hypothesised that if the mirror neuron system was impaired, reduced interference
      should be observed in the ASD group. However, control and ASD participants
      demonstrated an equivalent interference effect in an interpersonal condition,
      with greater movement variability in the incongruent compared to the congruent
      condition. A component of movement interference which is independent of
      congruency did differ between groups: ASD participants made generally more
      variable movements for the interpersonal task than for biological dot-motion
      task, while the reverse was true for the control participants. We interpret these
      results as evidence that the ASD participant group either rely to a greater
      extent on the goal-directed imitation pathway, supporting claims that they have a
      specific deficit of the non-goal-directed imitation pathway, or exhibit reduced
      visuomotor integration.

PMID- 18096191
TI  - Involvement of AMPA receptors in the antidepressant-like effects of lithium in
      the mouse tail suspension test and forced swim test.
AB  - In addition to its clinical antimanic effects, lithium also has efficacy in the
      treatment of depression. However, the mechanism by which lithium exerts its
      antidepressant effects is unclear. Our objective was to further characterize the
      effects of peripheral and central administration of lithium in mouse models of
      antidepressant efficacy as well as to investigate the role of alpha-amino-3
      hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in these behaviors.
      We utilized the mouse forced swim test (FST) and tail suspension test (TST),
      intracerebroventricular (ICV) lithium administration, AMPA receptor inhibitors,
      and BS3 crosslinking followed by Western blot. Both short- and long-term
      administration of lithium resulted in robust antidepressant-like effects in the
      mouse FST and TST. Using ICV administration of lithium, we show that these
      effects are due to actions of lithium on the brain, rather than to peripheral
      effects of the drug. Both ICV and rodent chow (0.4% LiCl) administration
      paradigms resulted in brain lithium concentrations within the human therapeutic
      range. The antidepressant-like effects of lithium in the FST and TST were blocked
      by administration of AMPA receptor inhibitors. Additionally, administration of
      lithium increased the cell surface expression of GluR1 and GluR2 in the mouse
      hippocampus. Collectively, these data show that lithium exerts centrally mediated
      antidepressant-like effects in the mouse FST and TST that require AMPA receptor
      activation. Lithium may exert its antidepressant effects in humans through AMPA
      receptors, thus further supporting a role of targeting AMPA receptors as a
      therapeutic approach for the treatment of depression.

PMID- 18096193
TI  - Disruptions in energy balance: does nature overcome nurture?
AB  - Fat accumulation, in general, is the result of a breakdown in the homeostatic
      regulation of energy balance. Although, the specific factors influencing the
      disruption of energy balance and why these factors affect individuals differently
      are not completely understood, numerous studies have identified multiple
      contributors. Environmental components influence food acquisition, eating, and
      lifestyle habits. However, the variability in obesity-related outcomes observed
      among individuals placed in similar controlled environments supports the notion
      that genetic components also wield some control. Multiple genetic regions have
      been associated with measures related to energy balance; however, the replication
      of these genetic contributors to energy intake and energy expenditure in humans
      is relatively small perhaps because of the heterogeneity of human populations.
      Genetic tools such as genetic admixture account for individual's genetic
      background in gene association studies, reducing the confounding effect of
      population stratification, and promise to be a relevant tool on the
      identification of genetic contributions to energy balance, particularly among
      individuals of diverse racial/ethnic backgrounds. Although it has been recognized
      that genes are expressed according to environmental influences, the search toward
      the understanding of nature and nurture in obesity will require the detailed
      study of the effect of genes under diverse physiologic and behavioral
      environments. It is evident that more research is needed to elucidate the
      methodological and statistical issues that underlie the interactions between
      genes and environments in obesity and its related comorbidities.

PMID- 18096194
TI  - Uptake of 4-chloro-2-methylphenoxyacetic acid (MCPA) from the apical membrane of
      Caco-2 cells by the monocarboxylic acid transporter.
AB  - The cellular uptake mechanism of 4-chloro-2-methylphenoxyacetic acid (MCPA), a
      phenoxyacetic acid derivative, was investigated using Caco-2 epithelial cells.
      The cells were incubated with 50 microM MCPA at pH 6.0 and 37 degrees C, and the
      uptake of MCPA from the apical membranes was measured. The uptake of MCPA was
      significantly decreased by incubation at low temperature (4 degrees C) and
      markedly increased by lowering the extracellular pH. Pretreatment with a
      protonophore, carbonylcyanide-p-(trifluoromethoxy)phenylhydrazone (25 microM), or
      metabolic inhibitors, 2,4-dinitrophenol (1 mM) and sodium azide (10 mM),
      significantly decreased the uptake of MCPA by 53%, 45% and 48%, respectively.
      Coincubation of MCPA with 10 mM l-lactic acid or alpha-cyano-4-hydroxycinnamate,
      which is a substrate or an inhibitor of the monocarboxylic acid transporters
      (MCTs), significantly decreased the uptake of MCPA by 31% and 20%, respectively,
      and coincubation with benzoic acid profoundly decreased the uptake by 68%. In
      contrast, coincubation with succinic acid (a dicarboxylic acid) did not affect
      the uptake. Kinetic analysis of initial MCPA uptake suggested that MCPA is taken
      up via a carrier-mediated process [Km=1.37+/-0.15 mM, Vmax=115+/-6 nmol (mg
      protein)(-1) (3 min)(-1)]. Lineweaver-Burk plots show that benzoic acid
      competitively inhibits the uptake of MCPA with a Ki value of 4.68 +/-1.76 mM. A
      trans-stimulation effect on MCPA uptake was found in cells preloaded with benzoic
      acid. These results suggest that the uptake of MCPA from the apical membrane of
      Caco-2 cells is mainly mediated by common MCTs along with benzoic acid but also
      in part by l-lactic acid.

PMID- 18096195
TI  - Glutathione level regulates HNE-induced genotoxicity in human erythroleukemia
      cells.
AB  - 4-hydroxy-trans-2-nonenal (HNE) is one of the most abundant and toxic lipid
      aldehydes formed during lipid peroxidation by reactive oxygen species. We have
      investigated the genotoxic effects of HNE and its regulation by cellular
      glutathione (GSH) levels in human erythroleukemia (K562) cells. Incubation of
      K562 cells with HNE (5-10 microM) significantly elicited a 3- to 5-fold increased
      DNA damage in a time- and dose-dependent manner as measured by comet assay.
      Depletion of GSH in cells by L-buthionine-[S,R]-sulfoximine (BSO) significantly
      increased HNE-induced DNA damage, whereas supplementation of GSH by incubating
      the cells with GSH-ethyl ester significantly decreased HNE-induced genotoxicity.
      Further, overexpression of mGSTA4-4, a HNE-detoxifying GST isozyme, significantly
      prevented HNE-induced DNA damage in cells, and ablation of GSTA4-4 and aldose
      reductase with respective siRNAs further augmented HNE-induced DNA damage. These
      results suggest that the genotoxicity of HNE is highly dependent on cellular
      GSH/GST/AR levels and favorable modulation of the aldehyde detoxification system
      may help in controlling the oxidative stress-induced complications.

PMID- 18096196
TI  - Drug-loaded nano/microbubbles for combining ultrasonography and targeted
      chemotherapy.
AB  - A new class of multifunctional nanoparticles that combine properties of polymeric
      drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound
      mediated drug delivery has been developed. At room temperature, the developed
      systems comprise perfluorocarbon nanodroplets stabilized by the walls made of
      biodegradable block copolymers. Upon heating to physiological temperatures, the
      nanodroplets convert into nano/microbubbles. The phase state of the systems and
      bubble size may be controlled by the copolymer/perfluorocarbon volume ratio. Upon
      intravenous injections, a long-lasting, strong and selective ultrasound contrast
      is observed in the tumor volume indicating nanobubble extravasation through the
      defective tumor microvasculature, suggesting their coalescence into larger,
      highly echogenic microbubbles in the tumor tissue. Under the action of tumor
      directed ultrasound, microbubbles cavitate and collapse resulting in a release of
      the encapsulated drug and dramatically enhanced intracellular drug uptake by the
      tumor cells. This effect is tumor-selective; no accumulation of echogenic
      microbubbles is observed in other organs. Effective chemotherapy of the MDA MB231
      breast cancer tumors has been achieved using this technique.

PMID- 18096197
TI  - Temperate bacteriophage PhiO18P from an Aeromonas media isolate: characterization
      and complete genome sequence.
AB  - A group of 74 Aeromonas isolates from surface water of three ponds in Bielefeld,
      Germany was screened for prophage induction after UV irradiation. The phage
      PhiO18P was induced from the Aeromonas media isolate O18. PhiO18P belongs to the
      Myoviridae phage family. The complete nucleotide sequence of the double stranded
      DNA genome of bacteriophage PhiO18P consists of 33,985 bp. The genome has 5'
      protruding cohesive ends of 16 bases. On the PhiO18P genome 46 open reading
      frames (orfs) were identified which are organized in the modules integration and
      regulation, replication, head, packaging, tail and lysis. Additionally the phage
      DNA includes a methylase gene. Comparison of the genome architecture with those
      of other bacteriophages revealed significant similarities to the P2 phage family
      and especially to the prophages of Aeromonas salmonicida and the Vibrio cholerae
      phage K139.

PMID- 18096198
TI  - Choice reaction times for identifying the direction of first-order motion and
      different varieties of second-order motion.
AB  - This study sought to quantify the temporal properties of the human visual system
      by measuring forced-choice reaction times for discriminating the drift direction
      of first-order motion (luminance-modulated noise) and a variety of second-order
      motion patterns (modulations of either the contrast, polarity, orientation or
      spatial length of a noise carrier) over a range of stimulus modulation depths. In
      general, reaction times for all types of second-order motion were slower than
      those for first-order motion. Specifically, reaction times were similar for
      modulations of image contrast, polarity and orientation but were markedly slower
      for modulations of spatial length. There was also a tendency for reaction times
      to decrease as stimulus modulation depth increased. The rate of this decrease was
      shallowest for first-order, luminance-defined patterns. For second-order motion
      reaction times decreased at a similar rate for contrast, polarity and orientation
      but this decrease was steepest for spatial length. However, when equated in terms
      of visibility (multiples of direction-discrimination threshold), the rate at
      which reaction times decreased as modulation depth increased became comparable
      for patterns defined by luminance, contrast, polarity and orientation. For
      patterns defined by spatial length, performance could not be equated in this
      manner. These findings demonstrate that the time taken to encode the direction of
      each pattern is not an invariant response metric. The results are consistent with
      psychophysical and electrophysiological evidence for longer response latencies
      for second-order motion and may reflect the additional processing stages (e.g.
      filter-rectify-filter) required for its extraction.

PMID- 18096199
TI  - Effects of aerobic and anaerobic conditions on P, N, Fe, Mn, and Hg accumulation
      in waters overlaying profundal sediments of an oligo-mesotrophic lake.
AB  - Concentrations of key nutrients and metals in water overlaying profundal
      sediments were evaluated in replicate experimental chambers containing
      undisturbed sediment-water interface samples from Deer Lake, an oligo-mesotrophic
      lake in eastern Washington. Chambers were incubated under three sequential
      phases: aerobic (21d), anaerobic (27d), and second aerobic (14d). In general,
      nutrients and metals in chamber water were lower under aerobic versus anaerobic
      conditions. However, in some cases compounds anticipated to appear only under
      anaerobic conditions, including ammonia, phosphate, and manganese, were observed
      during aerobic conditions. Correlation analysis elucidated a number of
      interactions between compounds. Phosphate correlated significantly (p<0.05) with
      iron during all incubation phases, suggesting that phosphorus cycling was
      controlled by iron. Cycling of nitrate and ammonia was tightly and significantly
      coupled under aerobic conditions. During both aerobic phases, nitrate increased
      while ammonia decreased, likely as a result of biological nitrification. Finally,
      mercury appeared during mildly reducing conditions and showed a significant
      correlation with manganese during the anaerobic phase, suggesting that Mn oxide
      reduction was the source of Hg in chamber water.

PMID- 18096200
TI  - Probing reactivity and substrate specificity of both subunits of the dimeric
      Mycobacterium tuberculosis FabH using alkyl-CoA disulfide inhibitors and acyl-CoA
      substrates.
AB  - The dimeric Mycobacterium tuberculosis FabH (mtFabH) catalyses a Claisen-type
      condensation between an acyl-CoA and malonyl-acyl carrier protein (ACP) to
      initiate the Type II fatty acid synthase cycle. To analyze the initial covalent
      acylation of mtFabH with acyl-CoA, we challenged it with mixture of C6-C20 acyl
      CoAs and the ESI-MS analysis showed reaction at both subunits and a strict
      specificity for C12 acyl CoA. Crystallographic and ESI-MS studies of mtFabH with
      a decyl-CoA disulfide inhibitor revealed a decyl chain bound in acyl-binding
      channels of both subunits through disulfide linkage to the active site cysteine.
      These data provide the first unequivocal evidence that both subunits of mtFabH
      can react with substrates or inhibitor. The discrepancy between the observed C12
      acyl-CoA substrate specificity in the initial acylation step and the higher
      catalytic efficiency of mtFabH for C18-C20 acyl-CoA substrates in the overall
      mtFabH catalyzed reaction suggests a role for M. tuberculosis ACP as a
      specificity determinant in this reaction.

PMID- 18096201
TI  - A method for measuring the anoxic biodegradability under denitrifying conditions.
AB  - A test for assessing the anoxic biodegradability of organic compounds under
      denitrifying conditions is proposed. The method is based on the recovery and
      quantification of the CO2 produced, which is evidence of complete biodegradation
      of the test compound (added as the sole carbon source). The tests were carried
      out in a mineral medium, with nitrate as electron acceptor. Whole lake sediments,
      sediment extracts and a commercial inoculum were assayed as a possible inoculum
      source by means of glucose biodegradability tests. It was found that the sediment
      extracts constitute a suitable and environmentally-relevant inoculum source,
      since they add non-significant amounts of carbon to the tests. Two xenobiotic
      compounds, namely, aniline and phenol, were tested in the aforementioned
      conditions as well as in a standard aerobic biodegradability test. Both aniline
      and phenol attained a biodegradation level higher than 60% in a short time period
      (<28 days) and thus can be considered as readily biodegradable in denitrifying
      environments. Nevertheless, the kinetics obtained in the anoxic test were slower
      than in aerobic conditions, and even suggested the accumulation of intermediate
      metabolites in the case of phenol. The results of this study indicate that the
      fate of xenobiotic compounds under anoxic conditions differs from that observed
      in an oxic environment, and therefore it should be considered by standard
      biodegradability testing procedures.

PMID- 18096202
TI  - Comparative and combined toxicities of toluene and methyl tert-butyl ether to an
      Asian earthworm Perionyx excavatus.
AB  - An earthworm assay was used to assess the toxicity of two main gasoline
      components. Ecotoxicities of toluene and methyl tert-butyl ether (MTBE) were
      compared for Asian earthworm Perionyx excavatus separately and in combination.
      Sum of toxic unit (TU) at 50% mortality for the mixture (LC50mix) was estimated
      from the dose (TU-based)-response relationships by the Trimmed Spearman-Karber
      method. Toluene was shown to be about five and two times more toxic to P.
      excavatus than MTBE in filter paper contact test and natural soil tests,
      respectively. This is primarily due to the adsorption of toluene to soil
      particles, leading to less bioavailability of toluene to the earthworm in soil.
      The combined effect of toluene and MTBE was investigated using toxic unit model,
      and it was found to be almost additive and synergistic responses to P. excavatus
      in filter paper contact test and soil tests, respectively. The combined effect of
      toluene and MTBE in filter paper contact test was not consistent with the results
      in soil toxicity tests. This phenomenon may be associated with the interaction of
      soil salts with pollutants. Treatment with toluene and MTBE also affected the
      behavior and morphology of P. excavatus. It indicates that the VOCs induce
      metabolic and functional damages in earthworms. Combined effects of gasoline
      components should be taken into account to soil risk assessment.

PMID- 18096203
TI  - Analysis of chlorothalonil and degradation products in soil and water by GC/MS
      and LC/MS.
AB  - We present a method using gas chromatography (GC) and liquid chromatography (LC)
      coupled to a mass selective detector to measure concentrations of the fungicide
      chlorothalonil and several of its metabolites in soil and water. The methods
      employed solid-phase extraction using a hydrophobic polymeric phase for the
      isolation of analytes. In lake water, average analyte recoveries ranged from 70%
      to 110%, with exception of pentachloronitrobenzene that gave low recoveries
      (23%). The method detection limits were determined to be in the range of 1 and
      0.1microg l(-1) for the LC and GC methods, respectively. In soil samples,
      recoveries ranged from 80% to 95% for 4-hydroxy-2,5,6-trichloroisophthalonitrile
      (metabolite II) and 1,3-dicarbamoyl-2,4,5,6-tetrachlorobenzene (metabolite III).
      Limits of detection (LOD) were 0.05 and 0.02microg g(-1), respectively.
      Chlorothalonil and other metabolites were analyzed by GC giving recoveries
      ranging from 54% to 130% with LOD of 0.001-0.005microg g(-1).

PMID- 18096204
TI  - Biological sweetening of energy gases mimics in biotrickling filters.
AB  - Removal of hydrogen sulfide from waste and energy-rich gases is required, not
      only because of environmental health and safety reasons, but also because of
      operational reasons if such gases have to be used for energy generation. A
      biotrickling filter for the removal of ultra-high concentrations of H2S from
      oxygen-poor gases is proposed and studied in this work. Two laboratory-scale
      biotrickling filters were used to study the startup period and to determine the
      long-term performance of the gas sweetening process. The inlet H2S concentration
      ranged from 900 to 12000ppmv and two different packing materials were
      investigated. There was no toxicity effect observed even at a the highest H2S
      concentration, and maximum elimination capacities of 280 and 250g H2Sm(-3)h(-1)
      were obtained at gas contact times of 167 and 180s, respectively. Elemental
      sulfur and sulfate were found to be the most abundant end-products of the
      biological oxidation of sulfide when operated under microaerophilic conditions.
      The biotrickling filter was able to quickly recover its nominal performance after
      different load increases and system shutdowns simulating field operation. The
      results reported here show that biotreatment can be an interesting alternative to
      conventional gas sweetening systems normally used for such applications.

PMID- 18096205
TI  - Variation in modern human premolar enamel formation times: implications for
      Neandertals.
AB  - A recent study demonstrated that variation in enamel cap crown formation in the
      anterior teeth is greater than that in the molars from two geographically
      distinct populations: native indigenous southern Africans and northern Europeans.
      Eighty southern African and 69 northern European premolars (P3 and P4) were
      analyzed in the present study. Cuspal, lateral, and total enamel formation times
      were assessed. Although cuspal enamel formation times were not consistently
      different between the two populations, both lateral and total enamel formation
      times generally were. Bonferroni-corrected t-tests showed that southern Africans
      had significantly shorter lateral enamel formation time for five of the six
      cusps, as well as significantly shorter total enamel formation time for these
      same cusps. An analysis of covariance performed on the lingual cusps of the upper
      third and fourth premolars showed that differences in enamel formation times
      between these populations remained when crown height was statistically
      controlled. A further goal of this study was to ascertain, based on perikymata
      counts, what Neandertal periodicities would have to be in order for their teeth
      to have lateral enamel formation times equivalent to either southern Africans or
      northern Europeans. To this end, perikymata were counted on 32 Neandertal
      premolars, and the counts were inserted into regression formulae relating
      perikymata counts to periodicity for each population and each tooth type.
      Neandertal enamel formation times could be equivalent to those of southern
      Africans or northern Europeans only if their hypothetical periodicities fall
      within the range of periodicities for African apes and modern humans (i.e., 6-12
      days). The analysis revealed that both populations could encompass Neandertal
      timings, with hypothetical periodicities based on the southern African population
      necessitating a lower range of periodicity (6-8 days) than those based on the
      northern European population (8-11 days).

PMID- 18096206
TI  - Benzene exposure in a sample of population residing in a district of Florence,
      Italy.
AB  - OBJECTIVE: Personal exposure to airborne benzene is influenced by various outdoor
      and indoor sources. The first aim of this study was to assess the benzene
      exposure of a sample of urban inhabitants living in an inner-city neighborhood of
      Florence, Italy, excluding exposure from active smoking. The secondary objective
      was to differentiate the personal exposures according to personal usage patterns
      of the vehicles. METHODS: A sample of 67 healthy non-smokers was monitored by
      passive samplers during two 4-weekday campaigns in winter and late spring.
      Simultaneously, benzene measurements were also taken for a subset of
      participants, inside and outside their houses. A 4-day time microenvironment
      activity diary was completed by each subject during each sampling period. Other
      relevant exposure data were collected by a questionnaire before the sampling.
      Additional data on urban ambient air benzene levels were also available from the
      public air quality network. The passive samplers, after automated thermal
      desorption, were analyzed by GC-FID. RESULTS: Benzene personal exposure levels
      averaged 6.9 (SD=2.1) and 2.3 (SD=0.7) microg/m(3) in winter and spring,
      respectively. Outdoor and indoor levels showed high correlation in winter and
      poor in spring. In winter the highest benzene personal exposure levels were for
      people traveling by more public transport, followed by users of only car and by
      users of only bus respectively. CONCLUSIONS: The time spent in-transport for work
      or leisure makes a major contribution to benzene exposure among Florentine non
      smoking citizens. Indoor pollution and transportation means contribute
      significantly to individual exposure levels especially in winter season.

PMID- 18096207
TI  - Buffering of recovery from acidification by organic acids.
AB  - In the United Kingdom, as in other regions of Europe and North America, recent
      decreases in surface water sulphate concentrations, due to reduced sulphur
      emissions, have coincided with marked increases in dissolved organic carbon (DOC)
      concentrations. Since many of the compounds comprising DOC are acidic, the
      resulting increases in organic acidity may have the potential to offset the
      benefits of a decrease in mineral (sulphate) acidity. To test this, we used a
      triprotic model of organic acid dissociation to estimate the proportional organic
      acid buffering of reduced mineral acidity as measured in the 22 lakes and streams
      monitored by the UK Acid Waters Monitoring Network. For an average non-marine
      sulphate decrease of 30 mueq l(-1) over 15 years from 1988-2003, we estimate that
      around 28% was counterbalanced by rising strong organic acids, 20% by rising
      alkalinity (partly attributable to an increase in weak organic acids), 11% by
      falling inorganic aluminium and 41% by falling non-marine base cations. The
      situation is complicated by a concurrent decrease in marine ion concentrations,
      and the impact this may have had on both DOC and acidity, but results clearly
      demonstrate that organic acid increases have substantially limited the amount of
      recovery from acidification (in terms of rising alkalinity and falling aluminium)
      that have resulted from reducing sulphur emissions. The consistency and magnitude
      of sulphate and organic acid changes are consistent with a causal link between
      the two, possibly due to the effects of changing acidity, ionic strength and
      aluminium concentrations on organic matter solubility. If this is the case, then
      organic acids can be considered effective but partial buffers to acidity change
      in organic soils, and this mechanism needs to be considered in assessing and
      modelling recovery from acidification, and in defining realistic reference
      conditions. However, large spatial variations in the relative magnitude of
      organic acid and sulphate changes, notably for low-deposition sites in
      northwestern areas where organic acid increases apparently exceed non-marine
      sulphate decreases, suggest that additional factors, such as changes in sea-salt
      deposition and climatic factors, may be required to explain the full magnitude of
      DOC increases in UK surface waters.

PMID- 18096208
TI  - Surgical management and adjuvant therapy for patients with uterine clear cell
      carcinoma: a multi-institutional review.
AB  - OBJECTIVE: To assess the role of surgical staging, adjuvant therapy, and
      cytoreduction in uterine clear cell carcinoma (UCCC). METHODS: A retrospective
      review was conducted at 2 major gynecologic cancer centers of all primary UCCC
      between 1982 and 2004. RESULTS: UCCC was confirmed in 99 patients. The 5-year
      overall survival (OS) was 79%, 77%, 47%, and 21% for stages I-IV respectively. 69
      patients had no gross evidence of extra-uterine disease, but 36 (52%) were
      upstaged at surgery. For those 22 patients with stages I and II disease who had a
      systematic lymphadenectomy (LND) (> 20 lymph nodes), no lymphatic (LF),
      peritoneal (PF), or hematological (HF) failures were noted. Radiation (RT)
      improved PFS (67 vs. 36%, p=0.02), and reduced pelvic sidewall recurrences (18
      vs. 53%, p=0.04) and vaginal failures (VF) (7 vs. 35%, p=0.04) for 45 patients at
      risk for LF (positive nodes or suboptimal LND). 39 patients with stages IIIC and
      IV disease were separately analyzed. Patients with no visible residual disease
      after cytoreduction had a significant improvement in median PFS (17 vs. 7 months,
      p<0.001), and OS (40 vs. 18 months, p=0.02) compared to patients with any
      residual disease after surgery. CONCLUSION: Comprehensive surgical staging with a
      systematic LND is essential to accurately define early stage UCCC. Vaginal
      brachytherapy may be adequate adjuvant therapy for stages I and II UCCC confirmed
      by systematic LND. Patients at risk for LF appear to benefit from pelvic RT. An
      effort at cytoreduction to no visible residual disease should be made in advanced
      UCCC when feasible.

PMID- 18096209
TI  - Outcome after combined modality treatment for uterine papillary serous carcinoma:
      a study by the Rare Cancer Network (RCN).
AB  - OBJECTIVES: Uterine papillary serous carcinoma (UPSC) is a rare subtype of
      endometrial carcinoma, characterized by a poor outcome. We sought to better
      analyze the effect of surgery and adjuvant therapies on this disease. METHODS: A
      retrospective analysis was performed on the records of 138 women diagnosed with
      UPSC between 1986 and 2003 in the framework of the Rare Cancer Network. RESULTS:
      Median age at diagnosis was 67 years. Pure UPSC was found in 107 patients and
      mixed histology in 30. Fifty-four patients had stage I, 20 stage II, 41 stage III
      and 23 stage IV disease. Median follow-up for the surviving patients was 44
      months. Surgery was performed in 129 patients, after which 122 were rendered free
      of gross disease and comprised the adjuvant group. Of these, 23 received platinum
      based chemotherapy. Radiotherapy was applied in 52 patients and 28 underwent
      combined chemo-radiotherapy. At last follow-up, 57 patients were alive free of
      disease, 10 were alive with disease, 62 died of disease, 8 died of other causes
      and 1 died due to toxicity. Five-year disease-free survival (DFS), disease
      specific survival (DSS) and overall survival for the 122 patients treated with
      curative intent were 42%, 56% and 54%, respectively. In multivariate analysis,
      age, stage, histology and adjuvant chemotherapy were significant for DFS; age,
      stage and histology were significant for DSS. Radiotherapy reduced the pelvic
      recurrence rate from 29% to 14% (p=0.047). CONCLUSIONS: UPSC harbours a moderate
      prognosis, with age, stage and histology as significant prognosticators.
      Conservative surgery followed by adjuvant chemotherapy and pelvic radiotherapy
      can be suggested as an appropriate treatment approach for patients treated with
      curative intent.

PMID- 18096210
TI  - Opportunities and challenges in ovarian cancer research, a perspective from the
      11th Ovarian cancer action/HHMT Forum, Lake Como, March 2007.
AB  - Advances in surgery and chemotherapy have improved the 5-year survival for
      patients with epithelial ovarian cancer, but have not impacted on the ultimate
      rate of cure in a disease that is diagnosed in late stage and that recurs in the
      majority of patients. "Omic" technologies promise to define genetically driven
      aberrant signaling pathways in malignant cells, provided that bioinformatic
      expertise can be focused on a cancer that is neither common nor rare. Molecular
      therapeutics must be linked to molecular diagnostics to permit individualized
      therapy. Not only epithelial cancer cells but also stroma, vasculature and the
      immune response must be targeted. Closer collaboration between academic
      institutions, biotech and pharma will be required to facilitate this process and
      to interest the private sector in an orphan disease. New preclinical models may
      permit more efficient development of drugs and siRNA that can target dormant drug
      resistant stem cells. Strategies must be developed to deal with the heterogeneity
      of different grades and histotypes. Identification of women at increased risk
      will facilitate prevention and early detection in subsets of patients. BRCA1/2
      might be sequenced in all ovarian cancer patients to identify new kindreds.
      Epidemiologic algorithms are being developed and validated. Awareness must be
      raised that oral contraceptives can reduce risk of developing ovarian cancer by
      50%. Early detection is likely to require panels of complementary biomarkers,
      analyzed by sophisticated statistical techniques, to improve sensitivity while
      maintaining extremely high specificity. As ovarian cancer becomes a chronic
      disease, greater emphasis will be placed on the challenges facing survivors.

PMID- 18096211
TI  - Reconciling molecular neuroendocrine signals and the scientists who study them.

PMID- 18096212
TI  - Differential effect of environment enrichment and social isolation on depressive
      like behavior, spontaneous activity and serotonin and norepinephrine
      concentration in prefrontal cortex and ventral striatum.
AB  - In order to determine the effect of postnatal environments on some behavioral and
      neurochemical depressive-like parameters, male Sprague-Dawley rats were reared
      from weaning in either social isolation, standard laboratory conditions, or
      environmental enrichment. Open-field activity was assessed at postnatal days 37,
      65, 93 and 107 and 1 h before the last open-field test, a forced-swimming test
      was carried out. After behavioral tests, the monoamines concentrations were
      analyzed in prefrontal cortex and ventral striatum. Relative to control and
      isolation rearing, the environmental enrichment reduced open-field activity, led
      to antidepressive-like effects and increased serotonin concentrations in the
      prefrontal cortex. Social isolation, on the other hand, did not affect open-field
      activity, but increased depressive-like behavior and reduced the amount of
      norepinephrine in the ventral striatum. Those neurochemical changes induced by
      rearing conditions correlated with the behavioral performance in the forced
      swimming test. Also, immobility behavior could be predicted by locomotor activity
      even from the first week of housing. Overall, specific variations in physical and
      social environment during early rearing lead to some behavioral and neurochemical
      alterations which might be relevant for understanding the role that
      neurodevelopmental and experiential factors could have in human depression.

PMID- 18096213
TI  - Interaction between cannabinoid compounds and diazepam on anxiety-like behaviour
      of mice.
AB  - Previous studies have suggested that cannabinoidergic system is involved in
      anxiety. However, a complete picture of cannabinoid association in the anxiety is
      still lacking. In the present study, we investigated the possible interaction
      between cannabinoidergic and GABAergic systems in the anxiety-like behaviour of
      mice. Intraperitoneal (i.p.) administration of the cannabinoid receptor agonist
      WIN55212-2 (0.25-5 mg/kg), the endocannabinoid transport inhibitor AM404 (0.25-2
      mg/kg) and diazepam (0.25-8 mg/kg) dose dependently exhibited an anxiolytic
      effect evaluated in terms of increase in the percentage of time spent in the open
      arms in the elevated plus maze (EPM) test. Administration of certain fixed-ratio
      combinations (3:1 and 1:1) of WIN55212-2 and diazepam produced a synergistic
      anxiolytic effect, while the 1:3 combination produced an additive effect. In hole
      board test, administration of certain ratios of WIN55212-2-diazepam combination
      significantly altered the animal behaviour compared to groups that received each
      drug alone. Co-administration of AM404 (1 and 2 mg/kg) and diazepam (0.5 mg/kg)
      abolished the anxiolytic effect of the former drug in EPM and the latter in hole
      board test, respectively. The combination of an ineffective dose of the fatty
      acid amide hydrolase (FAAH) inhibitor, URB597 (0.3 mg/kg, i.p.) on anxiety
      related responses with an ineffective dose of diazepam (0.25 mg/kg, i.p.) led to
      a synergistic effect. Co-administration of the CB1 receptor antagonist, AM251 (5
      mg/kg) and an effective dose of diazepam (2 mg/kg, i.p.) attenuated diazepam
      induced elevation of percentage of time spent in open arm, while lower dose of
      AM251 (0.5 mg/kg) failed to inhibit diazepam-induced anxiolytic effect. Taken
      together, the present study showed that co-administration of exogenous
      cannabinoids and diazepam produce additive or synergistic effect at different
      combinations. Moreover, it has been shown that enhancement of the function of
      endocannabinoids could increase the anxiolytic effect of diazepam.

PMID- 18096215
TI  - Neuroprotective actions of vitamin C related to decreased lipid peroxidation and
      increased catalase activity in adult rats after pilocarpine-induced seizures.
AB  - In the present study, we examined the neuroprotective effects of vitamin C in
      adult rats after pilocarpine-induced seizures. Vitamin C is an exogenous
      antioxidant that can be used in treatment of seizures. It can alter oxidative
      stress and damage neuronal induced by seizures. Its antioxidant properties can be
      proved in epilepsy models, such as pilocarpine-induced seizures in adult rats. In
      order to investigate neuroprotective effects of vitamin C, adult male rats (2
      months-old) were pretreated with vitamin C (VIT C 250 mg/kg, i.p.) 30 min before
      receiving pilocarpine (400 mg/kg, s.c., P400 group). The other three groups were
      treated with vitamin C (VIT C group) and saline 0.9 (control group) alone. The
      pretreatment with vitamin C increased the latency to first seizures and reduced
      mortality rate after pilocarpine-induced seizures. Pretreatment with vitamin C
      alone decrease lipid peroxidation levels when compared to pilocarpine group and
      P400+VIT C. In P400, P400+VIT C and VIT C groups were observed an increased
      hippocampal catalase activity when compared to control group. Our results can
      suggest that neuroprotective effects of vitamin C in adult rats can be the result
      of reduced lipid peroxidation levels and increase of catalase activity after
      seizures and status epilepticus induced by pilocarpine.

PMID- 18096216
TI  - Equity of access to physical activity facilities in an English city.
AB  - OBJECTIVE: To examine associations between household income, access to sports
      facilities and gyms, and physical activity in an English city. METHOD: A cross
      sectional geographical study was conducted in six neighbourhoods in the city of
      Norwich in August and September 2004. Participants were (n=401) adults who
      received, completed, and returned questionnaires. Road distances to facilities
      were calculated using Geographical Information System. RESULTS: For all facility
      types except gyms, mean income was lowest amongst those living farthest away.
      Compared to those with the lowest incomes, the most affluent participants lived
      on average just over 0.5 km closer to a facility of any type, 1 km closer to a
      sports facility but 900 m farther from a gym (all p<0.001). In general, those
      living farther from facilities reported that they were less active although they
      did not tend to report a desire to exercise more. CONCLUSION: People in low
      income households, who are more likely to adopt low levels of activity, are least
      well served by affordable facilities that would enable them to become more
      active. If the British Government is to meet targets for improving levels of
      physical activity, it may need to consider how market forces might be creating an
      inequitable distribution of facility provision.

PMID- 18096214
TI  - The effects of inhaled acetone on place conditioning in adolescent rats.
AB  - INTRODUCTION: Acetone is an ubiquitous ingredient in many household products
      (e.g., glue solvents, air fresheners, adhesives, nail polish, and paint) that is
      putatively abused; however, there is little empirical evidence to suggest that
      acetone alone has any abuse liability. Therefore, we systematically investigated
      the conditioned response to inhaled acetone in a place conditioning apparatus.
      METHOD: Three groups of male, Sprague-Dawley rats were exposed to acetone
      concentrations of 5000, 10,000 or 20,000 ppm for 1 h in a conditioned place
      preference apparatus alternating with air for 6 pairing sessions. A place
      preference test ensued in an acetone-free environment. To test the preference of
      acetone as a function of pairings sessions, the 10,000 ppm group received an
      additional 6 pairings and an additional group received 3 pairings. The control
      group received air in both compartments. Locomotor activity was recorded by
      infrared photocells during each pairing session. RESULTS: We noted a dose
      response relationship to acetone at levels 5000-20,000 ppm. However, there was no
      correlation of place preference as a function of pairing sessions at the 10,000
      ppm level. Locomotor activity was markedly decreased in animals on acetone-paired
      days as compared to air-paired days. CONCLUSION: The acetone concentrations we
      tested for these experiments produced a markedly decreased locomotor activity
      profile that resemble CNS depressants. Furthermore, a dose response relationship
      was observed at these pharmacologically active concentrations, however, animals
      did not exhibit a positive place preference.

PMID- 18096217
TI  - Exploring dual identification among Muslim-American emerging adults: a mixed
      methods study.
AB  - This mixed methods study explored dual identification among Muslim-American
      emerging adults of immigrant origin. A closer look was taken at the relationship
      between American and Muslim identifications and how this relationship was
      influenced by experiences of discrimination, acculturative and religious
      practices, and whether it varied by gender. Data were gathered from 97 Muslim
      Americans (ages 18-25) who completed a survey and produced identity maps, a
      pictorial representation of hyphenated identities. The findings showed that young
      people found a way of allowing their Muslim and American identities to co-exist,
      and only a small minority of the participants seemed to experience identity
      conflict. While religiosity was the only predictor of Muslim identification,
      young peoples' identification with mainstream United States culture was predicted
      by discrimination-related stress and acculturative practices. Gender moderated
      the relationship between Muslim and American identities in both survey measures
      and identity maps.

PMID- 18096218
TI  - Structural intermediates of acid unfolded Con-A in different co-solvents:
      fluoroalcohols and polyethylene glycols.
AB  - A molten globule-like intermediate of Con-A was obtained when subjected to acid
      unfolding. At pH 2 the intermediate was found to have native-like secondary
      structure, somewhat denatured tertiary structure and maximum ANS binding. Further
      the stability of this intermediate was studied in presence of fluoroalcohols (TFE
      and HFIP) and polyethylene glycols (PEG-400, 4000 and 20,000). Secondary
      structural changes were monitored by far-UV CD while alterations in the tertiary
      structure of the acid unfolded intermediate were probed by near-UV CD. To study
      the environment and position of the tryptophan residues present intrinsic
      fluorescence studies were performed. ANS binding studies were also made to know
      the extent of exposure of the hydrophobic patches. Using the above-mentioned
      techniques it was found that in presence of fluoroalcohols the pH 2 intermediate
      was transformed to a state with predominant alpha-helical secondary and denatured
      tertiary structures. In the pathway of these transformations MG-like
      intermediates were formed at 10% TFE and 6% HFIP. The folding intermediate of Con
      A obtained at pH 2 underwent a series of conformational changes when exposed to
      different molecular weight PEGs. Secondary structure was induced by low molecular
      weight PEG-400 and low concentrations of PEG-4000 and PEG-20,000 while at higher
      concentrations transition in structure was observed. Tertiary structure was
      stabilized only at low concentrations of PEG-400. PEG-4000 and PEG-20,000 in the
      whole concentration range resulted in the loss of tertiary structure.

PMID- 18096219
TI  - The use of thermal treatments to enhance the mechanical properties of electrospun
      poly(epsilon-caprolactone) scaffolds.
AB  - Nonwoven nanofiber scaffolds fabricated by electrospinning technology have been
      widely used for tissue engineering applications. Although electrospun nanofiber
      scaffolds fulfill many requirements for tissue engineering applications, they
      sometimes lack the necessary biomechanical properties. To attempt to improve the
      biomechanical properties of electrospun poly(epsilon-caprolactone) (PCL)
      scaffolds, fibers were bonded by thermal treatment. The thermal fiber bonding was
      performed in Pluronic F127 solution at a range of temperatures from 54 degrees C
      to 60 degrees C. Thermally bonded electrospun PCL scaffolds were characterized by
      analyzing the changes in morphology, fiber diameter, pore area, tensile
      properties, suture retention strength, burst pressure strength, and compliance.
      The biomechanical properties of the thermally bonded electrospun PCL scaffolds
      were significantly increased without any gross observable and ultrastructural
      changes when compared to untreated PCL scaffolds. This study suggests that the
      introduction of thermal fiber bonding to electrospun PCL scaffolds improved the
      biomechanical properties of these scaffolds, making them more suitable for tissue
      engineering applications.

PMID- 18096220
TI  - Intracellular delivery of core-shell fluorescent silica nanoparticles.
AB  - Highly fluorescent core-shell silica nanoparticles made by the modified Stober
      process (C dots) are promising as tools for sensing and imaging subcellular
      agents and structures but will only be useful if they can be easily delivered to
      the cytoplasm of the subject cells. This work shows that C dots can be
      electrostatically coated with cationic polymers, changing their surface charge
      and enabling them to escape from endosomes and enter the cytoplasm and nucleus.
      As an example of cellular delivery, we demonstrate that these particles can also
      be complexed with DNA and mediate and trace DNA delivery and gene expression.

PMID- 18096221
TI  - Bioresorption behavior of tetracalcium phosphate-derived calcium phosphate cement
      implanted in femur of rabbits.
AB  - One primary focus of the present study was to clarify the crucial resorption
      location relationship of a recently developed single-phase TTCP-derived calcium
      phosphate cement (CPC) implanted in rabbit femur in a systematic and quantitative
      way. Gross examination of retrieved CPC/bone composite samples indicated that the
      CPC implant did not evoke inflammatory response, necrosis or fibrous
      encapsulation in surrounding bony tissues. Histological examination revealed
      excellent CPC-host bone bonding. At 4 weeks, the resorption-induced voids between
      terminals of bone defects and implants were largely filled with new bone. CPC
      resorption, new blood vessels, osteocytes, osteons and osteoblast-like cells
      lining up with active new bone were observed at remodeling sites. At 12 weeks, a
      new bone network was developed within femoral defect, while CPC became islands
      incorporated in the new bone. At this stage, crevices filled with lamellar new
      bone structure were frequently observed. At 24 weeks, bone ingrowth and
      remodeling activities became so extensive that the interface between residual
      cement and new bone became less identifiable. In general, at all implant
      locations the resorption ratio values increased with implantation time, while at
      all implantation times the resorption ratios decreased from the exterior
      (cortical site) to the interior (cancellous site) of implants. At the end of 24
      weeks, CPC was almost completely resorbed and bone remodeling almost finished at
      the cortical site.

PMID- 18096222
TI  - The role of nanometer and sub-micron surface features on vascular and bone cell
      adhesion on titanium.
AB  - The quantified contribution of pure nanometer (features less than 100 nm in both
      the lateral and vertical scale) and sub-micron (features larger than 100 nm in
      the lateral scale) surface structures on the adhesion of vascular (endothelial)
      and bone (osteoblasts) cells were demonstrated in this study. Compared with flat
      titanium surfaces, sub-micron surface features led to a 27% increase in surface
      energy and promoted endothelial cell adhesion density by 200%. In addition,
      nanometer surface features also led to a 10% increase in surface energy and a 50%
      increase in endothelial cell adhesion density compared to flat titanium surfaces.
      Using aligned patterns of such features on titanium, it was clearly identified
      that both endothelial and bone cells selectively adhered onto sub-micron and
      nanometer surface features by 400% and 50% more than onto flat regions,
      respectively. Thus, the surface patterns developed in this study clearly
      confirmed that sub-micron to nanometer titanium surface features enhanced
      cytocompatibility properties for both endothelial and bone cells. Although sub
      micron features on titanium had the highest surface energy and the greatest cell
      adhesion densities, nanometer surface features in this study were more efficient
      surface features increasing both surface energy and cell adhesion more with
      respect to smaller changes in surface area and surface roughness (compared to sub
      micron surface features on titanium which had considerably larger changes in
      surface area and surface roughness).

PMID- 18096223
TI  - Effects of decellularization on the mechanical and structural properties of the
      porcine aortic valve leaflet.
AB  - The potential for decellularized aortic heart valves (AVs) as heart valve
      replacements is based on the assumption that the major cellular immunogenic
      components have been removed, and that the remaining extracellular matrix (ECM)
      should retain the necessary mechanical properties and functional design. However,
      decellularization processes likely alter the ECM mechanical and structural
      properties, potentially affecting long-term durability. In the present study, we
      explored the effects of an anionic detergent (sodium dodecyl sulfate (SDS)),
      enzymatic agent (Trypsin), and a non-ionic detergent (Triton X-100) on the
      mechanical and structural properties of AV leaflets (AVLs) to provide greater
      insight into the initial functional state of the decellularized AVL. The overall
      extensibility represented by the areal strain under 60 N/m increased from 68.85%
      for the native AV to 139.95%, 137.51%, and 177.69% for SDS, Trypsin, and Triton X
      100, respectively, after decellularization. In flexure, decellularized AVLs
      demonstrated a profound loss of stiffness overall, and also produced a nonlinear
      moment-curvature relation compared to the linear response of the native AVL.
      Effective flexural moduli decreased from 156.0+/-24.6 kPa for the native AV to
      23.5+/-5.8, 15.6+/-4.8, and 19.4+/-8.9 kPa for SDS, Trypsin, and Triton X-100
      treated leaflets, respectively. While the overall leaflet fiber architecture
      remained relatively unchanged, decellularization resulted in substantial
      microscopic disruption. In conclusion, changes in mechanical and structural
      properties of decellularized leaflets were likely associated with disruption of
      the ECM, which may impact the durability of the leaflets.

PMID- 18096224
TI  - Subcutaneous alemtuzumab for Sezary Syndrome in the very elderly.
AB  - Sezary Syndrome (SS) is an aggressive T-cell malignancy often presenting in
      advanced age and associated with poor prognosis. There is no standard therapy and
      because of co-morbidities, elderly patients are particularly challenging to
      treat. Alemtuzumab is an anti-CD52 monoclonal antibody that has activity in SS
      but is profoundly immunosuppressive, leading to great hesitation about its use in
      older patients. We treated five octogenarian patients with SS with subcutaneous
      (SQ) alemtuzumab, at relapse or as initial therapy, for 5-9 weeks. With the
      exception of transient grade 1-2 hematological toxicity and asymptomatic
      cytomegalovirus (CMV) (two patients) and Epstein-Barr virus (EBV) (one patient)
      reactivation, no other toxicities were observed. The clinical and hematological
      complete response (CR) rate was 100%. Three patients achieved durable responses
      (8+ to 17+ months). Alemtuzumab was safely administered and showed significant
      activity in very elderly SS patients.

PMID- 18096225
TI  - Common features of myeloproliferative disorders with t(8;9)(p12;q33) and CEP110
      FGFR1 fusion: report of a new case and review of the literature.
AB  - The 8p12 myeloproliferative syndrome is a rare, generally aggressive chronic
      myeloproliferative disorder (MPD). The hallmark of this MPD is the disruption of
      the FGFR1 gene, which encodes a tyrosine kinase receptor for members of the
      fibroblast growth factor family. In MPD cells FGFR1 is fused to several partners.
      The most frequent partner genes are BCR, CEP110, FOP, and ZNF198, localized on
      22q11, 9q33, 6q27, and 13q12, respectively. We report here the tenth case of
      translocation (8;9)(p12;q33) in an acute myelomonocytic leukemia and provide a
      review of the literature that points to common syndrome features: the
      t(8;9)(p11;q33) MPD transforms rapidly, and always in myelomonocytic leukemia,
      with a possible B- or T-lymphoid involvement, which may include tonsil invasion.
      The FGFR1-MPD seems refractory to current chemotherapies and is not sensitive to
      imatinib. Currently, only the patients with bone marrow transplantation stand a
      chance of survival.

PMID- 18096226
TI  - Low efficacy of thalidomide in improving response after induction in multiple
      myeloma patients who are candidates for high-dose therapy.
AB  - Giving the impact of complete response (CR) on outcome of multiple myeloma
      patients addressed to high-dose melphalan, we explored the role of a pre
      transplant intensification with 3 months thalidome plus dexamethasone therapy
      (Thal-Dex), after pulse-VAD induction. Seventy-four multiple myeloma patients (MM
      pts) uniformly treated, were retrospectively studied. The response rate after
      pulse-VAD were: CR 6%, VGPR 40%, PR 23%, MR 23%, and progression 8%. The response
      rate after Thal-Dex were similar: CR 11%, VGPR 39%, PR 17%, MR 9%, and
      progression 24%. Giving no advantage in terms of response rate with an additive
      toxicity, Thal-Dex does not seem useful for intensification before transplant.

PMID- 18096227
TI  - Oblique chest views as a routine part of skeletal surveys performed for possible
      physical abuse--is this practice worthwhile?
AB  - OBJECTIVE: To evaluate the utility of oblique chest views in the diagnosis of rib
      fractures when used as a routine part of the skeletal survey performed for
      possible physical abuse. METHODS: Oblique chest views have been part of the
      routine skeletal survey protocol at Primary Children's Medical Center since
      October 2002. Dictated radiology reports since that time were reviewed, and all
      cases with rib fractures documented were chosen for study. For each chosen case
      two pediatric radiologists identified and recorded rib fractures using only the
      PA and lateral chest radiographs (standard two-view chest series) from the
      skeletal survey for each case. In a separate session they identified and recorded
      rib fractures using the PA, lateral, right oblique, and left oblique radiographs
      (four-view chest series) from the skeletal survey for each case. The results were
      compared. RESULTS: Twenty-two cases with rib fractures were identified.
      Interpretation of the four-view chest series was different than interpretation of
      the two-view chest series in 12 of the 22 cases (54%). Overall, the four-view
      chest series differed significantly in the number of rib fractures diagnosed
      compared with the two-view chest series (p=.02, Wilcoxon matched-pairs signed
      rank test) adding 19 rib fractures and excluding 6 rib fractures. CONCLUSIONS:
      The results indicate that use of the four-view chest series adds information to
      that obtained from the two-view chest series and increases the accuracy of
      diagnosing rib fractures in cases of possible physical abuse. Addition of oblique
      chest views to the routine protocol for skeletal surveys performed for possible
      physical abuse is recommended.

PMID- 18096228
TI  - Trauma resilience among youth in substitute care demonstrating sexual behavior
      problems.
AB  - OBJECTIVE: The purpose of this longitudinal study was to examine the relationship
      between several proposed protective factors and trauma symptoms among highly
      vulnerable youth in the child welfare system. METHODS: Participants were 142
      youth identified with a sexual behavior problem and their caregivers. Two waves
      of data were collected for each participant an average of 18 months apart. Foster
      parents reported on perceived level of support from the child welfare agency,
      youth involvement in club activities, and perception of youths' interpersonal and
      emotional competence. Youth provided self-reports of their sexual and physical
      abuse experiences, trauma symptoms at both time 1 and time 2, and ratings of
      parenting practices. RESULTS: Youth with higher rates of sexual abuse showed more
      negative affect and higher levels of sexual and non-sexual rumination at time 2,
      controlling for time 1 scores. Boys and youth who experienced better parenting
      practices displayed lower negative affect. Youth with higher levels of emotional
      and interpersonal competence showed lower levels of non-sexual rumination.
      Moderation analyses revealed that youth with more significant sexual abuse
      histories whose foster parents did not feel supported by their child welfare
      caseworkers had higher levels of sexually ruminative thoughts. Finally, the
      results revealed that only youth without sexual abuse histories experienced the
      benefits of club involvement in terms of lower sexual rumination scores.
      CONCLUSIONS: This study demonstrated that youth with significant vulnerabilities
      can still exhibit a degree of protection from trauma symptomatology in the
      presence of a wide range of personal and social variables. These findings support
      the efforts of stakeholders to promote strengths at the level of the individual,
      family, and broader social network and community.

PMID- 18096229
TI  - Annetocin and TCTP expressions in the earthworm Eisenia fetida exposed to PAHs in
      artificial soil.
AB  - The toxicity of sublethal polycyclic aromatic hydrocarbons (PAHs) levels in soils
      was assessed by testing their impact on expression of annetocin, a reproduction
      regulating gene, and translationally controlled tumor protein (TCTP), a
      tumorigenic response gene, in the earthworm Eisenia fetida cultured in artificial
      soil spiked with, phenanthrene (Phe), pyrene (Pyr), fluoranthene (Flu), or
      benzo(a)pyrene (Bap). Annetocin and TCTP were both up-regulated by 0.1 and 1.0 mg
      kg(-1) benzo(a)pyrene and TCTP was down-regulated by 10.0 mg kg(-1) phenanthrene.
      Weight loss and cocoon production of the worms were also analyzed. Only 10.0 mg
      kg(-1) phenanthrene impacted earthworm weight loss significantly and no
      significant differences on cocoon production were observed. Our study indicated
      that the potential ecotoxicity of sublethal PAHs in soil should not be neglected
      and mRNA transcription level in earthworms was a more sensitive indicator of PAHs
      exposure than traditional indexes using cocoon production as endpoints and/or
      using the whole-organism as the test materials.

PMID- 18096231
TI  - Myxofibrosarcoma of the orbit: an underrecognized entity? Case report and review
      of the literature.
AB  - PURPOSE: To describe the clinicopathologic and immunohistochemical features of a
      rare case of myxofibrosarcoma (MFS) involving the orbit. DESIGN: Retrospective
      interventional case report and review of literature. METHODS: The clinical
      history, systemic imaging studies, and histopathologic results of the orbital
      biopsy are reviewed. MAIN OUTCOME MEASURES: Clinical, radiologic, and histologic
      features of MFS. RESULTS: A 63-year-old Chinese male sought treatment for a
      history of rapidly progressive proptosis associated with decreased vision in the
      left eye over 10 days. Magnetic resonance imaging of the orbit revealed a
      homogenous mass extending to the optic canal. The mass was excised partially and
      was submitted for histologic and ultrastructural examination. Histologic testing
      revealed features of MFS with characteristic diffuse proliferation of atypical,
      spindle-shaped fibroblasts with prominent myxoid stroma. Tumor cells were
      reactive for vimentin. Ultrastructural examination revealed spindle-shaped tumor
      cells, rich in dilated rough endoplasmic reticulum and prominent vacuoles.
      CONCLUSIONS: For historical reasons, MFS involving the orbit is likely to be
      underrecognized and categorized erroneously as malignant fibrous histiocytoma or
      other soft tissue sarcoma. Although orbital MFS is an extremely rare diagnosis,
      ophthalmologists should be aware of the possibility and consider a diagnosis of
      MFS when an adult seeks treatment for an orbital tumor with aggressive growth.

PMID- 18096230
TI  - The tick-over theory revisited: formation and regulation of the soluble
      alternative complement C3 convertase (C3(H2O)Bb).
AB  - The molecular interactions between the components of the C3 convertase of the
      alternative pathway (AP) of complement and its regulators, in both surface-bound
      and fluid-phase form, are still incompletely understood. The fact that the AP
      convertase is labile makes studies difficult to perform. According to the so
      called tick-over theory, hydrolyzed C3, called C3(H(2)O), forms the initial
      convertase in fluid phase together with factor B. In the present study, we have
      applied western blot analysis and ELISA together with fluorescence resonance
      energy transfer (FRET) to study the formation of the fluid-phase AP convertases
      C3(H(2)O)Bb and C3bBb and their regulation by factor H and factor I at specific
      time points and, with FRET, in real time. In our hands, factor B showed a higher
      affinity for C3(H(2)O) than for C3b, although in both cases it was readily
      activated to Bb. However, the convertase activity of C3bBb was approximately
      twice that of C3(H(2)O)Bb, as monitored by the generation of C3a. But in
      contrast, the C3(H(2)O)Bb convertase was more resistant to inactivation by factor
      H and factor I than was the C3bBb convertase. Under conditions that totally
      inactivated C3bBb, C3(H(2)O)Bb still retained approximately 25% of its initial
      activity.

PMID- 18096232
TI  - Filtering blebs and aqueous pathway an immunocytological and in vivo confocal
      microscopy study.
AB  - OBJECTIVE: To characterize and understand, at the cellular level, the aqueous
      humor pathways after filtering surgery, using in vivo confocal microscopy and
      impression cytology (IC). DESIGN: Observational case series. PARTICIPANTS: Thirty
      two blebs of 29 patients after trabeculectomy were retrospectively evaluated.
      METHODS: In vivo confocal microscopy and immunofluorescence staining of IC
      samples taken on and around the bleb area were performed. Impression cytology
      samples were examined under confocal microscopy after goblet cell and
      inflammatory cell immunostaining with anti-MUC5AC and antivimentin antibodies,
      respectively. Eyes were classified into 3 groups: (1) functioning blebs (11
      eyes), (2) nonfunctioning blebs (10 eyes), and (3) functioning blebs after
      mitomycin C application (12 eyes). Impression cytology specimens and in vivo
      confocal microscopy images were analyzed and compared in a masked manner. MAIN
      OUTCOME MEASURES: Conjunctival epithelium changes of each type of bleb were
      analyzed using both impression cytology specimens and in vivo confocal microscopy
      and correlated to clinical outcomes. RESULTS: In all IC specimens, numerous
      MUC5AC-positive cells were observed outside the edges of the blebs. Few MUC5AC
      positive cells were observed at the surface of nonfunctioning blebs. Numerous
      goblet cells with immunostaining that was weak or limited to the membrane were
      clearly visible morphologically at the surface of functioning blebs (with and
      without adjunctive mitomycin C). Using in vivo confocal microscopy, all
      functioning blebs showed numerous intraepithelial optically empty microcysts,
      whereas nonfunctioning blebs had none or only a few. All blebs contained
      dendritiform inflammatory cells, especially after mitomycin C application.
      CONCLUSION: Impression cytology and in vivo confocal microscopy provide a new
      approach to filtering blebs. Microcysts observed at the surface of functioning
      blebs seemed to correspond to goblet cells, mostly containing aqueous humor
      instead of highly hydrophilic gel-forming mucins. Although this hypothesis
      requires further confirmation, the transcellular pathway of the aqueous humor
      could be hypothesized to occur at the level of goblet cells toward the ocular
      surface.

PMID- 18096233
TI  - Topographic comparison of the visual function on multifocal visual evoked
      potentials with optic nerve structure on heidelberg retinal tomography.
AB  - PURPOSE: The authors' objective was to compare the visual field obtained using
      multifocal visual evoked potential (mfVEP) testing with the optic nerve
      parameters of Heidelberg retinal tomography (HRT; Heidelberg Engineering,
      Heidelberg, Germany; software version 2.01) in primary open-angle glaucoma (POAG)
      patients and normal controls and to determine which parameters correlate with
      visual function. DESIGN: Cross-sectional study. PARTICIPANTS: Eighty-one eyes of
      42 adult POAG patients and normal controls between the ages of 40 and 80 years,
      of which 35 patients (67 eyes; mean age+/-standard deviation [SD], 68+/-10 years)
      had POAG, and 7 individuals who served as normal controls (14 eyes; mean age+/
      SD, 61+/-10 years) were included. METHODS: A monocular mfVEP test, the AccuMap
      (Opera software version 2.0; ObjectiVision Pty. Ltd., Sydney, Australia), with a
      58-sector pattern-reversal dart board array was recorded in both eyes per
      patient. These patients underwent the HRT 2 and mfVEP tests within 3 months of
      each other. MAIN OUTCOME MEASURES: Amplitudes in the superior hemisphere of the
      mfVEP trace were compared with the HRT parameters in the inferior hemisphere of
      the HRT and vice versa using mixed effects regression models. RESULTS: Amplitudes
      on the superior hemisphere of the mfVEP recordings showed a significant direct
      correlation with rim-to-disc area ratio (P = 0.0037), rim volume (P = 0.0421),
      and mean retinal nerve fiber layer (RNFL) thickness (P = 0.0016) and a
      significant inverse correlation with cup area (P = 0.0009) and cup-to-disc area
      ratio (P = 0.0037) in the inferior hemisphere of the HRT results. Amplitudes on
      the inferior hemisphere showed a significant direct correlation with rim-to-disc
      area ratio (P = 0.036) and a significant inverse correlation with cup area (P =
      0.0007), cup-to-disc area ratio (P = 0.036), cup volume (P<0.0001), and mean cup
      depth (P = 0.0012) in the superior hemisphere of the HRT results. CONCLUSIONS:
      Results from mfVEP and HRT showed correlation between visual function and optic
      nerve structure.

PMID- 18096234
TI  - Vitamin usage patterns in the prevention of advanced age-related macular
      degeneration.
AB  - OBJECTIVE: To describe micronutrient usage patterns among patients at a tertiary
      ophthalmic center. DESIGN: Cross-sectional clinical case series. PARTICIPANTS:
      Three hundred thirty-two adult patients with a diagnosis of age-related macular
      degeneration (AMD). METHODS: Participants were surveyed about micronutrient usage
      patterns. The treating ophthalmologist recorded AMD severity using the Age
      Related Eye Disease Study (AREDS) classification system. MAIN OUTCOME MEASURES:
      Responses to study questionnaire and level of AMD severity. RESULTS: Among 332
      participants, 309 (93%) were using supplements, among which 174 (52%)
      supplemented with an AREDS-like formulation. Of these 174, 140 (80%) were
      considered AREDS supplement candidates based on study guidelines. Applying AREDS
      supplementation guidelines to the full cohort, 228 (69%) were candidates for
      supplementation. Only 140 (61%) of these individuals were confirmed to be using
      the correct formulation and dosage; an additional 13 (6%) used the AREDS
      formulation but were not using the recommended dosage. CONCLUSIONS: Among
      patients receiving care for AMD at a tertiary retinal center, more than one third
      of those deemed candidates for AREDS-type supplements were not using them or were
      using an incorrect dose. Furthermore, nearly one fifth of participants who were
      using high-dose supplements did not have a level of AMD anticipated to benefit
      from usage. Increased patient education is needed regarding the recommendations
      of AREDS.

PMID- 18096235
TI  - Synthesis of a new gadolinium complex with a high affinity for human serum
      albumin and its manifold physicochemical characterization by proton relaxation
      rate analysis, NMR diffusometry and electrospray mass spectrometry.
AB  - A novel gadolinium complex, derived from Gd-DTPA (DTPA:
      diethylenetriaminepentaacetic acid) and sulfaphenazole, intended to be a
      potential MRI contrast agent and to interact with human serum albumin (HSA), was
      synthesized and characterized. Its relaxometric properties were evaluated in
      water, and its binding to HSA was investigated by three techniques: proton
      relaxation rate analysis, NMR diffusometry, and electrospray mass spectrometry.
      The complex has a higher relaxivity than the parent compound (r(1)=7.8s(-1)mM(-1)
      at 310K and 0.47T and 7.7s(-1)mM(-1) at 310K and 1.41T), a fast water exchange,
      and a very good stability versus zinc(II) transmetallation. All techniques agree
      with a high affinity of the complex for HSA, and competition experiments indicate
      that this contrast agent competes with ibuprofen for HSA.

PMID- 18096236
TI  - Evaluation of in-house and commercial immunoassays for the sero-diagnosis of
      brucellosis in a non-endemic low prevalence population.
AB  - The Brucella Reference Unit (BRU) at the University Hospital Aintree offers a
      national Brucella sero-diagnosis service for England, Wales, Eire and Northern
      Ireland. The United Kingdom is a non-endemic area with a very low prevalence of
      infection. The objective of this study was to evaluate new CE marked assays,
      Brucellacapt (Vircell) and Brucella IgG and IgM ELISAs (Vircell), against the
      standard set of in-house serological assays used at BRU. These include a micro
      agglutination (MAG) assay, in-house IgG and IgM assays and a complement fixation
      test (CFT). One hundred and forty-three archived serum samples were re-tested by
      both the commercial and in-house assays. Samples were divided into four distinct
      groups based on the most common clinical patterns of serological profiles seen
      (negative, clinically significant and two forms of clinical indeterminate
      results). The kappa test was calculated to determine the level of agreement
      between the commercial and in-house results. The kappa coefficient for
      Brucellacapt and MAG assays was 0.90 (95% CI 0.85, 0.95) giving a very good level
      of agreement. Discrepancies between positive MAG and Brucellacapt assay results
      (5.7%) occurred only in sera with weakly reactive MAG titres of <1:160. Similarly
      the kappa coefficient calculated for the IgG assays was 0.81 (95% CI 0.75, 0.87)
      also indicating good agreement. However, the kappa coefficient for the commercial
      and in-house IgM assays was poor at 0.38 (95% CI, 0.30, 0.46). The weak IgM
      correlation was associated in some instances, with a lack of use of IgG sorbent
      in the in-house assay resulting in false-negative results. In a low prevalence
      population, the combination of in-house and commercial immunoassays offers
      improvements in the sero-diagnosis of brucellosis.

PMID- 18096237
TI  - Human infections associated with wild birds.
AB  - INTRODUCTION: Wild birds and especially migratory species can become long
      distance vectors for a wide range of microorganisms. The objective of the current
      paper is to summarize available literature on pathogens causing human disease
      that have been associated with wild bird species. METHODS: A systematic
      literature search was performed to identify specific pathogens known to be
      associated with wild and migratory birds. The evidence for direct transmission of
      an avian borne pathogen to a human was assessed. Transmission to humans was
      classified as direct if there is published evidence for such transmission from
      the avian species to a person or indirect if the transmission requires a vector
      other than the avian species. RESULTS: Several wild and migratory birds serve as
      reservoirs and/or mechanical vectors (simply carrying a pathogen or dispersing
      infected arthropod vectors) for numerous infectious agents. An association with
      transmission from birds to humans was identified for 10 pathogens. Wild birds
      including migratory species may play a significant role in the epidemiology of
      influenza A virus, arboviruses such as West Nile virus and enteric bacterial
      pathogens. Nevertheless only one case of direct transmission from wild birds to
      humans was found. CONCLUSION: The available evidence suggests wild birds play a
      limited role in human infectious diseases. Direct transmission of an infectious
      agent from wild birds to humans is rarely identified. Potential factors and
      mechanisms involved in the transmission of infectious agents from birds to humans
      need further elucidation.

PMID- 18096238
TI  - Neurotensin receptors as modulators of glutamatergic transmission.
AB  - Functional studies have provided evidence supporting the concept that the
      tridecapeptide neurotensin (NT) acts in the central nervous system as a classical
      neurotransmitter and/or as an important modulator of neuronal signalling. The
      role of NT in the regulation of the striatal amino acidergic transmission, mainly
      by antagonising D2 receptor function, will be analysed. In addition, in different
      rat brain regions, including the basal ganglia, the contribution of NT receptors
      in modulating and reinforcing glutamate signalling will be shown including the
      involvement of interactions between NT and NMDA receptors. Since the enhancement
      of glutamate transmission and in particular the excessive activation of NMDA
      receptors, has been postulated to be an important factor in the induction of
      glutamate-mediated neuronal damage, the involvement of NT in the glutamate
      induced neurodegenerative effects will be discussed. Moving from these
      observations and in order to further investigate this issue, results from
      preliminary behavioural, functional and biochemical experiments will be presented
      on the putative neuroprotective effect obtained by the blockade of NT receptor 1
      (NTS1) via the systemic administration of the selective NTS1 antagonist SR48692
      in an in vivo animal model of Parkinson's disease [unilateral nigral 6
      hydroxydopamine (6-OHDA) induced lesion of the nigrostriatal pathway].

PMID- 18096239
TI  - A procedure for the rapid screening of Maillard reaction inhibitors.
AB  - A procedure for the rapid screening of inhibitors of glycation reaction, based on
      their ability to protect RNase against sugar induced inactivation of the enzyme
      is described. Glycation is implicated in variety of disorders including diabetes,
      atherosclerosis various micropathies yet is a slow process both in vivo and in
      vitro. In order to speed up glycation, the reaction was carried out at 60 degrees
      C using a thermostable protein RNase and ribose, a sugar that is known to react
      rapidly than glucose in the glycation reaction. It was observed that incubation
      of RNase with ribose at 60 degrees C in rapid inactivation of the enzyme with a
      parallel decrease in tyrosine fluorescence, enhancement in new fluorescence and
      hyperchromicity in the UV-region. No such alterations in the enzyme activity were
      observed when the incubation was carried out in absence of the sugar. Compounds
      and drugs that are known to act as inhibitors of glycation reaction restricted
      the ribose-induced inactivation of RNase. RNase immobilized on CNBr-activated
      Sepharose was also sensitive to exposure to ribose and appeared a better system
      to screen inhibitors of glycation from natural sources that contain substances
      that interfere with the assay of enzyme as well as in the study of post Amadori
      inhibitors of glycation.

PMID- 18096240
TI  - Object recognition analysis in mice using nose-point digital video tracking.
AB  - Preferential exploration of novel locations and objects by rodents has been used
      to test the effects of various manipulations on object recognition memory.
      However, manual scoring is time-consuming, requires extensive training, and is
      subject to inter-observer variability. Since rodents explore primarily by
      sniffing, we assessed the ability of new nose-point video tracking software
      (NPVT) to automatically collect object recognition data. Mice performed a novel
      object/novel location task and data collected by NPVT, two expert observers, and
      one inexperienced observer were compared. Percent time spent exploring the
      objects were correlated between the two expert observers and between NPVT and the
      two expert observers. In contrast, the inexperienced observer showed no
      correlation with either expert observer or NPVT. NPVT collected more reliable
      data compared to the inexperienced observer. NPVT and the expert observers gave
      similar group averages for arbitrarily assigned groups of mice, whereas the
      analysis of the inexperienced observer gave different results. Finally, NPVT
      generated valid results in a NO/NL experiment comparing mice expressing human
      apolipoprotein E3 versus E4, a risk factor for age-related cognitive decline.
      Video tracking with nose-point detection generates useful analyses of rodent
      object recognition task performance and possibly for other behavioral tests.

PMID- 18096241
TI  - Characterization of an improved double hemorrhage rat model for the study of
      delayed cerebral vasospasm.
AB  - Rats have been shown in several studies to develop delayed cerebral vasospasm
      after subarachnoid hemorrhage (SAH). However, the rat model has not yet been
      fully validated, and there are number of methodological issues. In this study, we
      present an improved double hemorrhage rat model for studies of delayed cerebral
      vasospasm. Double hemorrhage was induced at an interval of 24h using a PE-10
      catheter introduced into the cisterna magna through a parieto-occipital burr
      hole. Blood volumes consisted of 0.3/0.2 ml (Group 1) or 0.2/0.1 ml (Group 2).
      Regional cerebral blood flow (CBF) was measured with (14)C-IMP, and compared to a
      sham operated control group. Additionally, the diameter and cross-sectional area
      of basilar artery (BA) was measured microscopically at four different levels.
      Mortality in Group 1 was 40%, compared to 1.5% in Group 2 and further experiments
      focused on the latter. Immediately following the second hemorrhage, the vessel
      diameter and cross-sectional area of BA were not significantly changed, but by
      day 5 these had decreased to 64+/-3% and 39+/-4% of control (p<0.001),
      respectively. CBF changes were global, affecting all cerebral areas to a similar
      degree. Immediately following second SAH induction, CBF diminished to 62-73% of
      control (p<0.05). By day 1, CBF had slightly increased above normal (101-120%),
      but there was then a second progressive reduction in flow in all areas examined
      at day 5 reaching 70-85% of baseline (p<0.05). CBF then normalized by day 7 and
      9. In this study, we present a new technique for creation of double SAH leading
      to delayed cerebral vasospasm in rats.

PMID- 18096242
TI  - A gaze-contingent paradigm for studying continuous saccadic adaptation.
AB  - Saccadic eye movements are used to quickly and accurately orient our fovea within
      our visual field to obtain detailed information from various locations. The
      accuracy of these eye movements is maintained throughout life despite constant
      pressure on oculomotor muscles and neuronal structures by growth and aging; this
      maintenance appears to be a product of an adaptive mechanism that continuously
      accounts for consistent post-saccadic visual error, and is referred to as
      saccadic adaptation. In this paper, we present a new paradigm to test saccadic
      adaptation under circumstances that more closely resemble natural visual error in
      everyday vision, whereas previous saccadic adaptation paradigms study adaptation
      in a largely restricted form. The paradigm achieves this by positioning a
      stimulus panel atop an identically colored background relative to the gaze
      position of the participant. We demonstrate the paradigm by successfully
      decreasing participants' saccadic amplitudes during a common visual search task
      by shifting the stimulus panel in the opposite direction of the saccade by 50% of
      the saccadic amplitude. Participants' adaptation reached approximately 60% of the
      50% back-shift during the adaptation phase, and was uniformly distributed across
      saccadic direction. The adaptation time-course found using the new paradigm is
      consistent with that achieved using previous paradigms. Task-performance results
      and the manner in which eye movements changed during adaptation were also
      analyzed.

PMID- 18096243
TI  - Predictors of suicidal acts across adolescence: influences of familial, peer and
      individual factors.
AB  - OBJECTIVE: To examine the influences of familial, peer and individual predictors
      of suicidal acts in a longitudinal study with a subset of school adolescents
      reporting high levels of depressive symptoms. METHOD: A representative sample of
      Norwegian school students (N=2464, mean age 13.7 years, T1) was reassessed after
      1 year (T2) with the same questionnaire. All high scorers of depressive symptoms
      on the Mood and Feelings Questionnaire (MFQ) at T2 were defined as cases. One
      control from low or middle scorers, matched for age and gender, was randomly
      assigned to every two cases. This subset (n=345) was diagnostically assessed by
      face-to-face K-SADS-PL interviews (mean age=14.9 years). The same subset was
      reassessed after 5 years (T3) by using the same questionnaire (n=252, mean
      age=20.0 years) and telephone K-SADS-PL interviews (n=242). The participation
      rate at T3 was 76.9% (n=265). The questionnaire explored various relationships
      with family members, peers and individual factors such as lifestyle habits, and
      physical health. RESULTS: Irrespective of time, history of a suicidal act
      significantly predicted a later suicidal act. Not living with both biological
      parents and a diagnosis of any depressive disorder were significant predictors
      for younger and older adolescents, respectively. CONCLUSIONS: In line with the
      findings of previous clinical studies, our results underline the importance of
      identifying previous suicidal acts, depressive disorders, broken homes and risk
      behaviours such as smoking and intoxication in the assessment of suicidal risk
      across adolescence.

PMID- 18096244
TI  - Autoantibody reactivity in serum of patients with major depression, schizophrenia
      and healthy controls.
AB  - The present study assessed 25 patients with unipolar major depression and 34
      patients with schizophrenia along with 50 healthy, non-psychiatric controls for
      the presence of serum antinuclear (ANA), smooth muscle (SMA), anti-endothelial
      (AEA), anti-sarcolemma (ASA), thyroid gland (TGA) and parietal cell (PCA)
      antibodies. In the group of patients with major depression, the frequency of
      elevated ANA, TGA and PCA was significantly higher than in the control group. In
      addition, the group of patients with schizophrenia significantly more often
      showed increased levels of ANA and SMA than the control group of healthy
      volunteers. When the two psychiatric groups were compared, PCA serum titers in
      major depression and SMA values in schizophrenia were significantly more
      frequently elevated, whereas values of AEA and ASA showed no difference. These
      results point towards the existence of an unspecific (auto) immune disposition or
      reaction in at least a subgroup of patients with major depression and
      schizophrenia.

PMID- 18096245
TI  - Cocaine and amphetamine regulated transcript (CART) in suicide attempters.
AB  - Cocaine and amphetamine regulated transcript (CART) is a neuropeptide expressed
      in brain regions thought to regulate anxiety levels, depression, addiction and
      energy homeostasis. Individuals with a CART mutation display increased anxiety
      and depression. Severe anxiety is a core phenomenon of suicidality. We therefore
      studied levels of CART in the cerebrospinal fluid (CSF) of 98 patients with
      different psychiatric diagnoses, shortly after a suicide attempt. We also
      investigated the relationship between CSF-CART and relevant psychiatric symptoms.
      CART levels were determined using a radioimmunoassay and the psychiatric symptoms
      rated in structured interviews using the Comprehensive Psychopathological Rating
      Scale (CPRS) and the Karolinska Scales of Personality (KSP). No differences in
      CSF-CART were found between the diagnostic groups or controls. However, lower
      CART levels were associated with a higher degree of concentration difficulties.
      No significant association was found between CART levels and other psychiatric
      symptoms. CSF-CART correlated significantly with CSF-levels of orexin, but not
      with corticotrophin releasing factor (CRF). Further studies on the role of CART
      in psychiatric diseases where concentration difficulties are prominent, such as
      attention deficit disorder, are warranted.

PMID- 18096246
TI  - Loudness dependence of the auditory evoked N1/P2 component as an indicator of
      serotonergic dysfunction in patients with schizophrenia--a replication study.
AB  - Serotonergic dysfunction appears to be involved in the pathogenesis of
      schizophrenia. The loudness dependence of auditory evoked potentials (LDAEP) has
      been suggested to be a valid indicator of the brain serotonin system's activity
      in humans. Patients with schizophrenia showed weaker LDAEP, indicating high
      serotonergic activity, in comparison to healthy controls. Thus, we were able
      again to demonstrate electrophysiological evidence for an upregulated
      serotonergic system in schizophrenia.

PMID- 18096247
TI  - Plasma apolipoprotein E is decreased in schizophrenia spectrum and bipolar
      disorder.
AB  - We have shown that plasma apolipoprotein E is significantly decreased in
      treatment-free subjects with schizophrenia spectrum and bipolar disorder but
      increases after treatment in bipolar disorder. Levels of apolipoprotein D were
      not changed by treatment. Hence changed apolipoprotein E could be involved in
      abnormalities in lipid homeostasis in some subjects with psychiatric diseases.

PMID- 18096248
TI  - Expression of Toll/IL-1R domain-containing adaptor protein (TIRAP) is detrimental
      to primary clearance of Salmonella and is not required for the generation of
      protective immunity.
AB  - Salmonella infection triggers activation of innate immune cells through the
      interaction of bacterial products with Toll-like receptors (TLRs). Toll/IL-1R
      domain-containing adaptor protein (TIRAP) is an adaptor protein involved in
      downstream signaling through TLRs 1, 2, 4, and 6. We examined the role of TIRAP
      during infection with attenuated Salmonella. Surprisingly, TIRAP-deficient mice
      were fully capable of resolving primary infection with Salmonella and actually
      exhibited accelerated clearance of bacteria at a late stage of the infection.
      Consistent with enhanced bacterial clearance, TIRAP-deficient mice resolved
      bacterial-associated splenic inflammation more rapidly than wild-type (Wt) mice
      and splenocytes from Salmonella-infected TIRAP-deficient mice produced more IFN
      gamma upon in vitro re-stimulation. Upon secondary challenge, TIRAP-deficient and
      Wt mice displayed a similar level of protective immunity against virulent
      Salmonella. Together these data indicate that TIRAP-mediated signaling is
      completely dispensable for clearance of Salmonella infection, and actually has a
      mild deleterious effect upon the resolution of primary infection.

PMID- 18096249
TI  - A membrane-bound form of IL-4 enhances proliferation and antigen presentation of
      CD40-activated human B cells.
AB  - CD40-activated B (CD40-B) cells might be an attractive source of autologous
      antigen-presenting cells (APCs) for immunotherapy due to the ability to obtain
      them from peripheral blood and expand them in vitro. However, soluble IL-4 (sIL
      4) in B-cell culture may not represent the "immunological synapse" between B and
      CD4+ T cells. In this study, the K562 cell line, which expresses CD40L and
      membrane-bound IL-4 (mbIL-4), could induce higher B-cell proliferation and
      antigen-presenting surface molecules, including adhesion, costimulatory and HLA
      molecules, compared with sIL-4. The differentiation to plasmablasts was decreased
      in CD40-B cells treated with mbIL-4 (CD40-B/mbIL-4) based on flow cytometry
      analysis. Furthermore, CD40-B/mbIL-4 cells were as potent as mature dendritic
      cells in the allogeneic lymphocyte reaction and the ability to generate cytotoxic
      T lymphocytes specific for cytomegalovirus pp65 antigen in vitro. Our results
      suggest that mbIL-4 could be used to generate CD40-B cells as potent APCs for
      cellular vaccines and adoptive immunotherapy.

PMID- 18096250
TI  - Detection of minority variants within bovine respiratory syncytial virus
      populations using oligonucleotide-based microarrays.
AB  - Microarray technology, originally developed for highly parallel examination of
      gene expression is regarded as a potential tool in prognosis and diagnosis. With
      respect to a discrimination analysis, difference as small as one nucleotide base
      can be distinguished using oligonucleotide-based microarrays. However, this
      degree of specificity is dependent on several parameters, including the size of
      the oligoprobes and the sequence context of the probes (e.g. local melting
      temperature), hybridization conditions and to some extent the chemistry of the
      glass slides onto which the probes are deposited. Using bovine respiratory
      syncytial virus (BRSV) as a model study, an oligonucleotide-based microarray
      approach was developed to measure the relative abundance of a particular single
      nucleotide variant within mixed BRSV populations. Using this technology, we show
      that it is possible to discriminate at a rate of 1%, minority variants in a BRSV
      population.

PMID- 18096251
TI  - Treatment of Crimean-Congo hemorrhagic fever.
AB  - Crimean-Congo hemorrhagic fever (CCHF) has the most extensive geographic range of
      the medically significant tick-borne viruses, occurring from western China across
      southern Asia to eastern Europe and South Africa. The causative agent is a
      negative-sense, single-stranded RNA virus in the genus Nairovirus, family
      Bunyaviridae. In published reports, the case fatality rate has generally ranged
      from 10% to 50%. Sporadic cases and outbreaks of the disease have increased
      during the past decade across the endemic region. CCHF was first diagnosed in
      Turkey in 2002, but since then more than 1100 cases have been confirmed by IgM
      serology or RT-PCR, with a fatality rate of just over 5%. Simple methods are
      available for the in vitro evaluation of antiviral drugs, but because CCHF virus
      does not cause disease in its reservoir species or in laboratory animals other
      than suckling mice, methods are lacking for in vivo efficacy testing. Intravenous
      or oral ribavirin has been used in several countries to treat the disease for
      more than 20 years. Evidence of its efficacy is limited to observational studies,
      and placebo-controlled trials may be impossible to perform for ethical reasons.
      However, careful analysis of properly stratified observational studies can be
      used to assess the effects of treatment. This article reviews current approaches
      to the treatment of CCHF, focusing on the use of ribavirin and hematological
      support, and discusses prospects for future research.

PMID- 18096252
TI  - Thiol metabolism and antioxidant systems complement each other during arsenate
      detoxification in Ceratophyllum demersum L.
AB  - Ceratophyllum demersum L. is known to be a potential accumulator of arsenic (As),
      but mechanisms of As detoxification have not been investigated so far. In the
      present study, we analyzed the biochemical responses of Ceratophyllum plants to
      arsenate (As(V); 0-250 microM) exposure to explore the underlying mechanisms of
      As detoxification. Plants efficiently tolerated As toxicity up to concentrations
      of 50 microM As(V) and durations of 4 d with no significant effect on growth by
      modulating various pathways in a coordinated and complementary manner and
      accumulated about 76 microg As g(-1)dw. Significant increases were observed in
      the levels of various thiols including phytochelatins (PCs), the activities of
      enzymes of thiolic metabolism as well as arsenate reductase (AR). These primary
      responses probably enabled plants to detoxify at least some part of As(V) through
      its reduction and subsequent complexation. The maximum proportion of As chelated
      by PCs was found to be about 30% (at 50 microM As(V) after 2 d). Simultaneously,
      a significant increase in the activities of antioxidant enzymes was observed and
      hence plants did not experience oxidative stress when exposed to 50 microM As(V)
      for 4 d. Exposure of plants to higher concentrations (250 microM As(V)) and/or
      for longer durations (7 d) resulted in a significant increase in the level of As
      (maximum 525 microgg(-1)dw at 250 microM after 7 d) and an inverse relationship
      between As accumulation and various detoxification strategies was observed that
      lead to enhanced oxidative stress and hampered growth.

PMID- 18096253
TI  - Characterization of a PRL protein tyrosine phosphatase from Plasmodium
      falciparum.
AB  - Isoprenylated proteins have important functions in cell growth and
      differentiation of eukaryotic cells. Inhibitors of protein prenylation in malaria
      have recently shown strong promise as effective antimalarials. In studying
      protein prenylation in the malaria protozoan parasite Plasmodium falciparum, we
      have shown earlier that the incubation of P. falciparum cells with (3)H-prenol
      precursors resulted in various size classes of labeled proteins. To understand
      the physiological function of prenylated proteins of malaria parasites, that are
      targets of prenyltransferase inhibitors, we searched the PlasmoDB database for
      proteins containing the C-terminus prenylation motif. We have identified, among
      other potentially prenylated proteins, an orthologue of a PRL (protein of
      regenerating liver) subgroup protein tyrosine phosphatases, termed PfPRL. Here,
      we show that PfPRL is expressed in the parasite's intraerythrocytic stages, where
      it partially associates with endoplasmic reticulum and within a subcompartment of
      the food vacuole. Additionally, PfPRL targeting parallels that of apical membrane
      antigen-1 in developing merozoites. Recombinant PfPRL shows phosphatase activity
      that is preferentially inhibited by a tyrosine phosphatase inhibitor suggesting
      that PfPRL functions as a tyrosine phosphatase. Recombinant PfPRL can also be
      farnesylated in vitro. Inhibition of malarial farnesyltransferase activity can be
      achieved with the heptapetide RKCHFM, which corresponds to the C-terminus of
      PfPRL. This study provides the first evidence for expression of enzymatically
      active PRL-related protein tyrosine phosphatases in malarial parasites, and
      demonstrates the potential of peptides derived from Plasmodium prenylated
      proteins as malarial farnesyltransferase inhibitors.

PMID- 18096254
TI  - N-linked glycosylation of proteins in the protozoan parasite Toxoplasma gondii.
AB  - Toxoplasma gondii is an obligate intracellular parasite of animal cells.
      Infection of humans is common and may result in devastating disease, especially
      in immunocompromised individuals. Despite previous reports that N-glycosylation
      of proteins may be a rare post-translational modification in this and related
      organisms, we demonstrate that it is actually quite prevalent in Toxoplasma. N
      Glycosylation is completely inhibited by treatment of parasites with tunicamycin,
      but this does not appear to exert its major effect on the parasites until they
      have egressed from their host cells. Although the tunicamycin-treated parasites
      appear structurally normal at this time they are not motile and mostly incapable
      of invading new host cells. The few tunicamycin-treated parasites that do invade
      are severely affected in their ability to replicate and accumulate with a
      distended endoplasmic reticulum, deformed nuclei, and without recognizable late
      secretory organelles. We provide experimental evidence that indicate that
      Toxoplasma N-glycans differ structurally from those in other eukaryotes.

PMID- 18096255
TI  - Relationship between oral function and general condition among Japanese nursing
      home residents.
AB  - The purpose of this study was to clarify the relationship between oral function
      and general condition among Japanese nursing home residents. The hypothesis was
      that oral function is one of the most important factors for the maintenance of
      general condition in dependent elderly. Seventy-nine residents of a nursing home
      in Japan participated in this study (54 women and 25 men, age range: 65-95 years,
      mean age: 82.2+/-8.5). A water drinking test and gargling function were used as
      indicators of oral function. Indicators of general condition included cognitive
      function (mini-mental state examination; MMSE), ADL (Barthel index), and
      nutritional status (body mass index=BMI, and serum albumin level). To clarify the
      relationship between oral function and general condition among dependent elderly,
      statistical evaluations of correlations (Spearman rank correlation coefficient)
      and differences (Mann-Whitney U test, Student's t test) between groups were
      conducted. SPSS was used for the statistical analysis. The water drinking and
      gargling function tests showed a strong correlation (p<0.001) with cognitive
      function and ADL. The water drinking and gargling function tests showed a
      correlation with BMI (p<0.005, p<0.01, respectively), and the water drinking test
      showed a correlation with serum albumin level (p<0.05). However, no correlation
      was observed between the gargling function tests and serum albumin level. It is
      concluded that oral function is closely related to cognitive function, ADL, and
      nutritional status. Oral function may play an important role in maintaining
      general condition in dependent elderly. To prevent decreases in cognitive
      function, ADL and nutritional status in dependent elderly, the importance of
      improvements in oral function cannot be over-emphasized.

PMID- 18096256
TI  - Aerosolized iloprost for postoperative pulmonary hypertensive crisis in children
      with congenital heart disease.
AB  - INTRODUCTION: Pulmonary hypertensive crisis (PHC) is a significant contributor to
      the morbidity and mortality of surgery for congenital heart defect. Management of
      such a potentially fatal complication has been evolving for the past decades.
      Inhaled iloprost has been reported as an alternative treatment for this
      condition. We evaluated the use of aerosolized iloprost as a rescue therapy for
      PHC in children undergoing congenital heart surgery. METHODS: In this clinical
      study, 12 high risk children were monitored in order to identify postoperative
      PHC after congenital heart repair. Factors being monitored included pulmonary
      artery pressure, systemic blood pressure, left atrial pressure, transcutaneous
      oximetry and heart rate. PHC was defined as an acute rise in pulmonary pressure
      which causes cardiopulmonary compromise as reflected by desaturation and
      hypotension. Despite conventional medical treatment to prevent postoperative PHC,
      children with PHC were therefore administered with aerosolized iloprost (0.5
      microg/kg). RESULT: Eight of the 12 children had one or more episodes of PHC,
      secondary to the pulmonary vasoreactivity. All responded to the aerosolized
      iloprost treatment, as demonstrated by a fall in their mean pulmonary pressure
      from 47.9 + or - 14.9 to 30.2 + or - 7.9 mmHg (p=0.012) and a rise in the
      arterial saturation from 82.2 + or - 16.7 to 93.4 + or - 11.5 % (p=0.012) while
      mean systemic blood pressure tended to increase from 59.4 + or - 12.1 to 64 + or 
      10.3 mmHg (p=0.16). CONCLUSION: In medical setting with limited access to the
      nitric oxide, inhaled iloprost is consider to be an effective alternative
      treatment for postoperative PHC in children undergoing congenital heart surgery.

PMID- 18096257
TI  - Serial angiographic and intravascular ultrasound analysis of late stent strut
      fracture of sirolimus-eluting stents in native coronary arteries.
AB  - BACKGROUND: Stent fracture in sirolimus-eluting stents (SES) has been reported to
      be associated with late adverse events. However, a suitable method to diagnose
      stent fracture is not fully elucidated. METHODS: One hundred and two consecutive
      SES implantations were performed in 83 lesions in 56 patients and underwent
      serial angiography with intravascular ultrasound (IVUS) at baseline and at 6
      months follow-up. Angiographic stent strut fracture was defined as stent bending
      with separation of stent struts. Angiographic hinge movement was defined as stent
      shaft deviation without separation of stent struts. IVUS stent strut dissociation
      was defined as the disappearance of stent struts in more than one cross-sectional
      image which were previously visualized at baseline. RESULTS: By angiography, no
      cases of stent fracture were detected at 6 months. One case of angiographic hinge
      movement was found at 12 months. However, three instances of stent fracture were
      detected by IVUS at 6 months. One case of stent fracture showed a patent lumen
      area at 6 months but subsequently developed late stent restenosis at 12 months.
      The other two cases were associated with in-stent restenosis at 6 months.
      CONCLUSION: Compared to angiography, IVUS can more reliably detect stent fracture
      during follow-up evaluation.

PMID- 18096258
TI  - Multiple-locus variable-number tandem-repeats analysis of Listeria monocytogenes
      using multicolour capillary electrophoresis and comparison with pulsed-field gel
      electrophoresis typing.
AB  - The multiple-locus variable-number tandem-repeats analysis (MLVA) method for
      genotyping has proven to be a fast and reliable typing tool in several bacterial
      species. MLVA is in our laboratory the routine typing method for Salmonella
      enterica subsp. enterica serovar Typhimurium and Escherichia coli O157. The gram
      positive bacteria Listeria monocytogenes, while not isolated as frequent as S.
      Typhimurium and E. coli, causes severe illness with an overall mortality rate of
      30%. Thus, it is important that any outbreak of this pathogen is detected early
      and a fast trace to the source can be performed. In view of this, we have used
      the information provided by two fully sequenced L. monocytogenes strains to
      develop a MLVA assay coupled with high-resolution capillary electrophoresis and
      compared it to pulsed-field gel electrophoresis (PFGE) in two sets of isolates,
      one Norwegian (79 isolates) and one Swedish (61 isolates) set. The MLVA assay
      could resolve all of the L. monocytogenes serotypes tested, and was slightly more
      discriminatory than PFGE for the Norwegian isolates (28 MLVA profiles and 24 PFGE
      profiles) and opposite for the Swedish isolates (42 MLVA profiles and 43 PFGE
      profiles).

PMID- 18096259
TI  - Identification and genetic fingerprinting of Brachyspira species.
AB  - Six Brachyspira type and reference strains, and 14 well characterized porcine
      field isolates representing all recognised porcine Brachyspira spp. were compared
      by different molecular methods. Sequence analysis of the 16S rRNA and the nox
      genes, pulsed-field gel electrophoresis (PFGE) and randomly amplified polymorphic
      DNA (RAPD) were used in the study. In addition the isolates were analysed by five
      species-specific PCR systems. The topologies of the dendrograms obtained from
      each of the four typing systems were different. The B. pilosicoli isolates formed
      monophyletic clusters in all dendrograms, but with different sister lines. All
      five porcine Brachyspira species formed monophyletic clusters in the nox gene
      based dendrogram only. All five PCR systems accurately identified their targets,
      except for the nox gene-based B. intermedia-specific system, by which it was not
      possible to identify one of the presumed B. intermedia isolates, and the other B.
      intermedia-specific system, based on the 23S rRNA gene, gave a positive reaction
      for one B. innocens isolate. In an extended study, 46 additional isolates and the
      original eight isolates with the phenotypes of B. hyodysenteriae or B. intermedia
      were compared by PFGE and PCR. The PFGE results indicated a high genetic
      diversity of isolates with the phenotype of B. intermedia. Thirty-three of 34
      tested isolates could be identified by one or both of the two B. intermedia
      specific PCR systems used, however, only 19 of the 34 isolates were positive in
      both systems.

PMID- 18096260
TI  - Monitoring biosensor capture efficiencies: development of a model using GFP
      expressing Escherichia coli O157:H7.
AB  - One of the known limitations for biosensor assays is the high limit of detection
      for target cells within complex samples (e.g., Escherichia coli at 10(4) to 10(5)
      CFU/mL) due to poor capture efficiencies. Currently, researchers can only
      estimate the cell capture efficiency necessary to produce a positive signal for
      any type of biosensor using either cumbersome techniques or regression modeling.
      To solve this problem, green fluorescent protein (GFP) transformed E. coli
      O157:H7 was used to develop a novel method for directly and easily measuring the
      cell capture efficiency of any given biosensor platform. For demonstration
      purposes, E. coli-GFP was assayed on both fiber optic and planar waveguide
      biosensor platforms. Cells were enumerated using an epifluorescent microscope and
      digital camera to determine the number of cells captured on the surfaces.
      Conversion algorithms were used with these digital images to determine the cell
      density of entire waveguide surface areas. For E. coli-GFP, the range of cell
      capture efficiency was between 0.4 and 1.2%. This indicates that although the
      developed model works for calculating cell capture, there is still need for
      significant improvements in capture methods themselves, to increase the capture
      efficiency and thereby lower detection limits. The use of GFP-transformed target
      cells and cell capture efficiency calculations can facilitate the development and
      optimization processes by allowing direct enumeration of new biosensor design
      configurations and sample processing strategies.

PMID- 18096261
TI  - Analysis of a choice-reaction task yields a new interpretation of Libet's
      experiments.
AB  - Benjamin Libet has demonstrated that the readiness potential precedes the time at
      which participants consciously decide to perform an intentional motor act, and
      suggested that free will is an illusion. We performed an experiment where
      participants observed a stimulus on a computer monitor and were instructed to
      press one of two buttons, depending on the presented stimulus. We found neural
      activity preceding the motor response, similar to Libet's experiments. However,
      this activity was already present prior to stimulus presentation, and thus before
      participants could decide which button to press. Therefore, we argue that this
      activity does not specifically determine behaviour. Instead, it may reflect a
      general expectation. This interpretation would not interfere with the notion of
      free will.

PMID- 18096262
TI  - Sequence analysis of mRNA transcripts encoding Jembrana disease virus Tat-1 in
      vivo.
AB  - Jembrana disease virus (JDV) is a lentivirus which replicates to very high titres
      in vivo and its Tat-1 protein has been shown to be a potent transactivator in
      vitro. Analysis of tat mRNA transcripts produced early in infection studies
      identified four predominant species which were generated by multiple splicing
      events. The use of a splice donor downstream of tat-1 was common indicating that
      a Tat-1 protein of 97 amino acids is expressed during the acute phase of Jembrana
      disease. The presence of an in-frame stop codon between tat-1 and tat-2 was
      identified in transcripts from three different strains of JDV confirming that
      expression of a single exon Tat-1 correlates with high viral titres in vivo.
      Sequence conservation in the regions of tat-1 that are critical for RNA binding
      and transcription activation in three different virus strains was high and the
      tat-2 sequences were completely conserved.

PMID- 18096263
TI  - A major EBNA1 variant from Asian EBV isolates shows enhanced transcriptional
      activity compared to prototype B95.8.
AB  - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) has an instrumental role in
      maintaining EBV latent infection by controlling EBV episome replication and
      regulating viral transcription. It is a ubiquitously expressed protein during
      latent viral infection and in EBV-associated tumors. The EBNA1 C-terminus
      interacts functionally with the Qp and Cp that control viral gene expression in
      latency I/II and III, respectively. EBNA1 has been classified into five subtypes
      due to sequence variation in the DNA-interacting C-terminus. By DNA sequence
      analysis of its C-terminus, we detected a main sub-variant (V-val-v1) of EBNA1
      with valine located in both positions 487 and 528 from matched samples including
      NPC biopsies and peripheral blood taken from Vietnamese (9), Chinese (12) NPC
      patients and healthy donors (5). In the FR-region of oriP from nine NPC biopsies
      from Vietnam we also frequently found substitutions, deletions and variable
      numbers of repeats. Using a luciferase reporter system, EBNA1 and FR both derived
      from Asian isolates induced higher transcriptional activity than those from B95-8
      virus.

PMID- 18096265
TI  - Na+/H+ exchanger inhibitor, FR183998, has protective effect in lethal acute liver
      failure and prevents iNOS induction in rats.
AB  - BACKGROUND/AIMS: Selective inhibition of Na(+)/H(+) exchanger (NHE) improves
      organ dysfunctions including heart ischemia-reperfusion injury. In vivo and in
      vitro studies were designed to investigate whether NHE inhibitor has a protective
      effect in lethal acute liver failure, and if so, what are the mechanisms
      involved. METHODS: NHE inhibitor (FR183998) was administered to rats treated with
      d-galactosamine/lipopolysaccharide (GalN/LPS), or incubated with cultured
      hepatocytes stimulated by pro-inflammatory cytokine, interleukin (IL)-1beta.
      RESULTS: FR183998 reduced the increases of pro-inflammatory cytokines such as TNF
      alpha, interferon-gamma and CINC-1, but enhanced the anti-inflammatory cytokine,
      IL-10, leading to the prevention of liver injury and increased survival rate in
      GalN/LPS-treated animals. FR183998 prevented the activation of transcription
      factor NF-kappaB induced by GalN/LPS. In vivo and in vitro experiments revealed
      that FR183998 reduced inducible nitric oxide synthase (iNOS) induction and NO
      production. Further FR183998 decreased levels of iNOS antisense-transcript in
      GalN/LPS-treated liver and IL-1beta-treated hepatocytes. CONCLUSIONS: FR183998
      may reduce a variety of inflammatory mediators such as cytokines and NO in part
      through the inhibition of NF-kappaB activation, resulting in the prevention of
      fulminant liver failure, and may inhibit iNOS gene expression at steps of iNOS
      promoter transactivation and its mRNA stabilization through NF-kappaB and iNOS
      antisense-transcript, respectively.

PMID- 18096266
TI  - Enhancement of genotype 1 hepatitis C virus replication by bile acids through
      FXR.
AB  - BACKGROUND/AIMS: Hepatitis C virus (HCV) infected patients with high serum levels
      of bile acids (BAs) usually fail to respond to antiviral therapy. Besides, BAs
      are essential factors for replication of the porcine enteric calicivirus by
      inhibiting interferon signaling. The role of BAs on HCV RNA replication was thus
      assessed. METHODS: BAs and other compounds were tested using an HCV-replication
      model containing a luciferase reporter gene. RESULTS: BAs, especially
      chenodeoxycholate and deoxycholate, up-regulated genotype 1 HCV RNA replication
      by more than tenfold. Only free but not conjugated BAs were active, suggesting
      that their effect was mediated by a nuclear receptor. Only farnesoid X receptor
      (FXR) ligands stimulated HCV replication while FXR silencing and FXR antagonism
      by guggulsterone blocked the up-regulation induced by BAs. Furthermore,
      guggulsterone alone inhibited basal level of HCV replication by tenfold.
      Modulation of HCV replication by FXR ligands occurred in the same proportion in
      presence or absence of type I interferon, suggesting a mechanism of action
      independent of this control of viral replication. However, BAs or guggulsterone
      did not affect replication of genotype 2a-JFH1. CONCLUSIONS: Exposure to
      routinely measured concentrations of BAs increases HCV replication by a novel
      mechanism involving activation of the nuclear receptor FXR.

PMID- 18096267
TI  - Natural history of chronic hepatitis B: special emphasis on disease progression
      and prognostic factors.
AB  - The natural history of chronic hepatitis B virus (HBV) infection and disease is
      complex and highly variable. We review the natural history of chronic hepatitis B
      with emphasis on the rates of disease progression and factors influencing the
      course of the liver disease. Chronic hepatitis B is characterized by an early
      replicative phase (HBeAg positive chronic hepatitis) and a late low or non
      replication phase with HBeAg seroconversion and liver disease remission (inactive
      carrier state). Most patients become inactive carriers after spontaneous HBeAg
      seroconversion with good prognosis, but progression to HBeAg negative chronic
      hepatitis due to HBV variants not expressing HBeAg occurs at a rate of 1-3 per
      100 person years following HBeAg seroconversion. The incidence of cirrhosis
      appears to be about 2-fold higher in HBeAg negative compared to HBeAg positive
      chronic hepatitis. In the cirrhotic patient the 5-year cumulative risk of
      developing hepatocellular carcinoma is 17% in East Asia and 10% in the Western
      Europe and the United States and the 5-year liver related death rate is 15% in
      Europe and 14% in East Asia. There is a growing understanding of viral, host and
      environmental factors influencing disease progression, which ultimately could
      improve the management of chronic hepatitis B.

PMID- 18096268
TI  - Generic causal probabilistic networks: a solution to a problem of transferability
      in medical decision support.
AB  - Causal probabilistic networks provide a natural framework for representation of
      medical knowledge, allowing clinical experts to encode assumptions about causal
      dependencies between stochastic variables. Application in medical decision
      support has produced promising results. However, model features and parameters
      may vary geo- or demographically. Therefore methods are needed that allow for
      easy adjustment of the model to a change in conditions. We present a method to
      represent causal probabilistic networks generically that maximizes the
      transferability of a models relevance and completeness, when moved from one
      environment to another, and illustrate application of the method with an example
      from a medical decision support system.

PMID- 18096269
TI  - Advances in lipid nanodispersions for parenteral drug delivery and targeting.
AB  - Parenteral formulations, particularly intravascular ones, offer a unique
      opportunity for direct access to the bloodstream and rapid onset of drug action
      as well as targeting to specific organ and tissue sites. Triglyceride emulsions,
      liposomes and micellar solutions have been traditionally used to accomplish these
      tasks and there are several products on the market using these lipid
      formulations. The broader application of these lipid systems in parenteral drug
      delivery, however, particularly with new chemical entities, has been limited due
      primarily to the following reasons: a) only a small number of parenteral lipid
      excipients are approved, b) there is increasing number of drugs that are
      partially or not soluble in conventional oils and other lipid solvents, and c)
      the ongoing requirement for site-specific targeting and controlled drug release.
      Thus, there is growing need to expand the array of targetable lipid-based systems
      to deliver a wide variety of drugs and produce stable formulations which can be
      easily manufactured in a sterile form, are cost-effective and at least as safe
      and efficacious as the earlier developed systems. These advanced parenteral lipid
      based systems are at various stages of preclinical and clinical development which
      include nanoemulsions, nanosuspensions and polymeric phospholipid micelles. This
      review article will showcase these parenteral lipid nanosystems and discuss
      advances in relation to formulation development, processing and manufacturing,
      and stability assessment. Factors controlling drug encapsulation and release and
      in vivo biodistribution will be emphasized along with in vitro/in vivo toxicity
      and efficacy case studies. Emerging lipid excipients and increasing applications
      of injectable lipid nanocarriers in cancer chemotherapy and other disease
      indications will be highlighted and in vitro/in vivo case studies will be
      presented. As these new parenteral lipid systems advance through the clinic and
      product launch, their therapeutic utility and value will certainly expand.

PMID- 18096270
TI  - Challenges and opportunities in the encapsulation of liquid and semi-solid
      formulations into capsules for oral administration.
AB  - The encapsulation of liquids and semi-solids provides solutions for convenient
      delivery through improved oral absorption of poorly water-soluble drugs. In
      addition, low dose (content uniformity), highly potent (containment), low melting
      point drugs, those with a critical stability profile and those for which a
      delayed release is required are candidates for liquid or semi-solid formulations.
      Both hard and soft capsules can be considered and in each case the capsule wall
      may comprise gelatin or some other suitable polymer such as hypromellose. The
      choice of a hard or soft capsule will depend primarily on the components of the
      formulation which provides the best absorption characteristics as well as on the
      physical characteristics, such as the viscosity of the formulation and the
      temperature at which the product needs to be filled. Numerous excipients are
      available for formulation of lipid-based systems and their compatibilities with
      hard gelatin capsules have been tested. The availability of new enhanced
      manufacturing equipment has brought new opportunities for liquid-filled hard
      capsules. Filling and sealing technologies for hard capsules, provides the
      formulator with the flexibility of developing formulations in-house from small
      scale, as required for Phase I studies, up to production.

PMID- 18096271
TI  - c-MYC antisense phosphosphorodiamidate morpholino oligomer inhibits lung
      metastasis in a murine tumor model.
AB  - BACKGROUND: c-MYC amplification and overexpression has been correlated with
      progression and chemotherapy resistance in lung cancer. AVI-4126, a neutral
      antisense phosphorodiamidate morpholino oligomer (PMO) has been identified to
      specifically inhibit c-MYC expression in multiple disease models and identified
      in Phase I clinical studies to be safe and bioavailable in solid tumors. The
      present study evaluates AVI-4126 on the development of lung metastasis in the
      LLC1 syngeneic murine tumor model. Further, this is the first study to show in
      vivo mis-splicing of c-MYC post-AVI-4126 treatment. METHODS AND RESULTS:
      Subcutaneous administration of AVI-4126 at local tumor site (50 microg/day) for 3
      cycles of 5 days a week starting day 1 post-tumor cell implantation showed
      significantly decreased tumor burden, number of tumorlets formed in the lung in
      comparison to saline or control PMO treatment groups, although no significant
      reduction of the subcutaneous tumor was observed. AVI-4126 treated lung had
      markedly reduced mitotic activity but higher rate of apoptosis compared to the
      controls. HPLC-based analysis of tumor and lung lysates confirmed the presence of
      intact PMO. In addition to decrease in c-MYC expression, a moderate reduction in
      the levels of MMP-9 mRNA, a pro-angiogenic extracellular matrix protein
      postulated to be involved in extravasation of cells from the localized tumor or
      implantation into the distant metastatic site was observed in the LLC1 tumor
      tissue of AVI-4126 treated animals. CONCLUSIONS: The study results are
      significant in the development of novel anti-tumoral therapeutic strategies
      directed to c-MYC-overexpressing tumors and establish AVI-4126 as a strong
      clinical candidate for metastatic disease.

PMID- 18096272
TI  - Flexible computational docking studies of new aminoglycosides targeting RNA 16S
      bacterial ribosome site.
AB  - Ribonucleic acids (RNAs) have only recently been viewed as a target for small
      molecules drug discovery. Aminoglycoside compounds are antibiotics which bind the
      ribosomal A site (16S fragment) and cause misreading of the bacterial genetic
      code and inhibit translocation. In this work, a complete molecular modeling study
      is done for 16 newly derived aminoglycoside compounds where diverse nucleoside
      fragments are linked. Docking calculations are applied to 16S RNA target and a
      weak linear correlation, between experimental and calculated data, is obtained.
      However, one particularity of RNA is its high flexibility. To mimic this
      behavior, all docking calculations are followed by small molecular dynamic
      simulations. This last computational step improves significantly the correlation
      with experimental data and allowed us to establish structure-activity
      relationships. The overall results showed that the consideration of the RNA
      dynamic behavior is of great interest.

PMID- 18096273
TI  - Synthesis and evaluation of new phosphonolipid compounds for gene delivery.
AB  - The preparation of a series of novel water soluble cationic lipid derivatives
      possessing phosphonate ester groups linked to the para-position of N-methyl
      pyridinium moieties and bearing either identical or different alkyl chains is
      reported. The obtained phospholipids were tested for transfection efficiency into
      three different mammalian cell lines alone and in conjunction with
      diphytanoylphosphatidylethanolamine (DiPPE) or dioleylphosphatidylethanolamine
      (DOPE), using an assay adapted for 96-well microplates based on the detection of
      a colorimetric change caused by the production of a chromogen induced by
      expressed secreted human placental alkaline phosphatase. In our conditions, the
      highest transfection activities of cells HEK293 and hard-to-transfect cell lines
      B16 and CHO were achieved with a 4-phosphonobutylpyridinium compound used at 1:5,
      1:10 or 3:6 DNA/lipid ratio bearing two myristyl chains in the presence of the
      fusogenic helper lipid DiPPE.

PMID- 18096274
TI  - [Angiotensin-converting enzyme inhibitor-related angioedema: emergency treatment
      with complement C1 inhibitor concentrate].
AB  - A man with no atopic antecedent, but who was being treated with a Angiotensin
      converting enzyme inhibitor (ACE), was admitted to hospital for an edema
      affecting the face and tongue. The symptoms included dyspnea and dysphagia but
      not pruritus or dermal erythema. The patient was resistant to corticoid
      treatment, antihistaminic drugs and epinephrine. Treatment with C1 inhibitor
      concentrate (1000u) made the clinical symptoms disappear within 20 minutes. The
      resulting angioedema induced seems to be linked to the bradykinin metabolism,
      which would not be any better served by the angiotensin-converting enzyme, which
      normally inactivates about 75% of it.

PMID- 18096275
TI  - [Stem cell transplantation in autoimmune diseases].

PMID- 18096277
TI  - Identifying B and T cell epitopes and studying humoral, mucosal and cellular
      immune responses of peptides derived from V antigen of Yersinia pestis.
AB  - Yersinia pestis is a Gram negative bacterium which causes bubonic and pneumonic
      plague. Out of the two protective antigens F1 and V as vaccine candidates, we
      focused our attention on V antigen as peptide-based immunogen. Eleven peptides of
      varying lengths were synthesized for mapping major antigenic sites on V antigen.
      Six peptides showed competition by three complimentary approaches (1) with anti-V
      sera, (2) with anti-peptide sera and (3) by direct binding assay. Peptides which
      showed competition were found to be highly immunogenic in terms of peak antibody
      titres (both IgG and IgA) with longer duration, showed predominantly IgG2a/IgG2b
      subclass distribution, high affinity/avidity indices with single immunization
      schedule through intranasal routes. After intranasal immunization, these peptides
      showed high IgA response in sera and SIgA in intestinal washes and
      bronchoalveolar lavages while intramuscular immunization failed to give mucosal
      response. Intramuscular immunization generated high titre antibodies (both IgG
      and IgA) in sera with negligible SIgA response in washes which required
      additional booster immunization. All the peptides sera reacted with V antigen in
      Western blot analysis. During T cell proliferation assay, five peptides showed
      lymphocyte proliferation response irrespective of how antigen priming and pulsing
      was done in three strains of mice. These five peptides also showed Th1 cytokine
      profile whereas rest of the peptides showed mixed Th1/Th2 response. Two peptides
      exclusively showed high levels of IL-10 production. Mathematical modeling of V
      antigen indicates that these peptides lie on the surface of the protein. In
      conclusion, peptides a, g and j are pure B cell epitopes; peptides d and k are
      pure T cell epitopes and peptides b, f and i showed both B and T cells property
      on V antigen.

PMID- 18096276
TI  - Vaccinia viruses with mutations in the E3L gene as potential replication
      competent, attenuated vaccines: intra-nasal vaccination.
AB  - Vaccinia virus (VACV) has been used as the vaccine to protect against smallpox,
      and recombinant VACVs have been used to develop vaccine candidates against
      numerous cancers and infectious diseases. Although relatively safe for use in
      humans, the strains of VACV that were used as smallpox vaccines led to several
      complications including, progressive infection in immune compromised individuals,
      eczema vaccination in individuals with a history of atopic dermatitis, and
      encephalitis and perimyocarditis in apparently healthy individuals. The work
      described in this paper focuses on attenuated strains of VACV that may have the
      potential for use as vaccine vectors with reduced pathogenicity. We have
      generated several VACV mutants in a WR background with specific mutations in the
      E3L gene that were at least a 1000-fold less pathogenic compared to wtVACV upon
      intra-nasal infection of mice. Many of these mutant viruses replicated to high
      titers in the nasal mucosa of mice following intra-nasal administration. Despite
      replication to high titers in the nose, there was little spread to other organs
      in infected animals. Intra-nasal vaccination with doses as low as 100-1000 pfu
      (plaque forming units) of these replicating VACV constructs were sufficient to
      protect the host from challenge with large doses of wtVACV. Similar constructs in
      a Copenhagen and a NYCBH background were highly attenuated, yet effective as
      vaccines in the mouse model. These recombinant VACV constructs may be promising
      vector candidates for use in vaccination strategies against smallpox and other
      pathogens.

PMID- 18096278
TI  - The Tat protein broadens T cell responses directed to the HIV-1 antigens Gag and
      Env: implications for the design of new vaccination strategies against AIDS.
AB  - We have previously shown that the biologically active Tat protein targets and
      efficiently enters dendritic cells, and increases the proteolytic activities of
      the immunoproteasome, thereby favoring the generation and presentation of the
      subdominant MHC-I binding CTL epitopes of heterologous antigens. In the present
      study, we demonstrate that Tat broadens in vivo epitope-specific T cell responses
      directed to heterologous antigens including HIV structural proteins.
      Specifically, co-immunization of mice with OVA and Tat proteins induces CTL
      responses against subdominant and cryptic OVA-derived epitopes, which are not
      detected in mice vaccinated with OVA alone. Similarly, mice vaccinated with the
      HIV-1 Gag, Env or V2-deleted Env antigens in combination with Tat show Th1-type
      and CTL responses directed to a larger number of T cell epitopes, as compared to
      mice vaccinated with these proteins in absence of Tat. In contrast, Tat did not
      affect Th2-type responses to these structural HIV proteins. These results
      indicate that Tat is not only an antigen but also a novel Th1-type adjuvant
      capable of broadening in vivo the spectrum of epitopes recognized by T cells, and
      suggest that Tat can be considered an optimal co-antigen in the development of
      novel vaccination strategies against AIDS.

PMID- 18096280
TI  - Environmental conditions for the formation of insoluble Tc in water ponds located
      above paddy fields.
AB  - Optimum conditions for the formation of insoluble Tc (Tc in >0.2 microm size
      fraction) were studied using a microcosm including water ponds above a paddy
      field to understand Tc behavior in such fields. In the microcosm, soluble TcO(4)(
      ) was converted to insoluble forms, but no changes in the form of Tc were
      observed in filtered microcosm samples which were microorganisms-free. The
      formation of insoluble Tc was inhibited by the addition of the antibiotic
      chloramphenicol. In addition, the reduction of soluble Tc(VII)O(4)(-) to low
      valence oxide was not observed in the filtered microcosm samples, although
      reducing conditions were present. These results indicated that bacteria were
      involved in the formation of insoluble Tc. Since oxidizing conditions influence
      bacterial metabolism, the formation of insoluble Tc by bacteria was studied under
      aerobic and anaerobic conditions. The results showed that anaerobic conditions
      were favorable for the formation of insoluble Tc. In addition, the addition of
      formate as an electron donor to a microcosm sample facilitated the formation of
      insoluble Tc. The results suggested that insoluble Tc in the water ponds above
      paddy fields was caused by bacteria, which were shown to couple the oxidation of
      formate to the reduction of Tc(VII) during anaerobic respiration.

PMID- 18096279
TI  - Generation and characterization of a preventive and therapeutic HPV DNA vaccine.
AB  - Cervical cancer is one of the most common cancers in women worldwide. Persistent
      infection with human papillomavirus (HPV) is considered to be the etiological
      factor for cervical cancer. Therefore, an effective vaccine against HPV
      infections may lead to the control of cervical cancer. An ideal HPV vaccine
      should aim to generate both humoral immune response to prevent new infections as
      well as cell-mediated immunity to eliminate established infection or HPV-related
      disease. In the current study, we have generated a potential preventive and
      therapeutic HPV DNA vaccine using human calreticulin (CRT) linked to HPV16 early
      proteins, E6 and E7 and the late protein L2 (hCRTE6E7L2). We found that
      vaccination with hCRTE6E7L2 DNA vaccine induced a potent E6/E7-specific CD8+ T
      cell immune response, resulting in a significant therapeutic effect against E6/E7
      expressing tumor cells. In addition, vaccination with hCRTE6E7L2 DNA generated
      significant L2-specific neutralizing antibody responses, protecting against
      pseudovirion infection. Thus, the hCRTE6E7L2 DNA vaccines are capable of
      generating potent preventive and therapeutic effects in vaccinated mice. Our data
      has significant clinical implications.

PMID- 18096282
TI  - Photographic documentation with a mobile phone camera.

PMID- 18096281
TI  - Delivery of a brief motivational intervention to patients with alcohol-related
      facial injuries: role for a specialist nurse.
AB  - In this paper we focus on providing an alcohol screening and intervention service
      within maxillofacial surgery. Two trained nurses screened patients with alcohol
      related facial injuries who attended maxillofacial outpatient clinics, and gave
      brief motivational interventions to those who had been drinking to a hazardous
      level. Patients were followed up at 3 and 12 months after the intervention.
      195/249 patients (78%) drank to a hazardous level. One hundred and ninety-five
      patients received an intervention. Duration of intervention was between 5 and 65
      minutes. Reasons for refusal to participate included lack of interest or time,
      and the main reason for exclusion was length of time since injury. The follow up
      rate was 103 (53%) at 3 months and 134 (69%) at 12 months. CONCLUSIONS: The high
      level of hazardous drinking among people with facial trauma suggests a clear need
      for alcohol screening and intervention. It is feasible for nursing staff to
      deliver brief interventions in a busy maxillofacial trauma clinic.

PMID- 18096283
TI  - Survival after diagnosis of cancer of the oral cavity.
AB  - In this retrospective study we analysed the survival in 470 patients with oral
      cancer. Patients who attended five university hospitals in Tehran, Iran, during
      the period 1996-2002 were included. Data were obtained from a combination of
      sources including patients' records, telephone calls, and deaths registered by
      the Ministry of Health. Survival curves were generated using Kaplan-Maier curves.
      Univariate and multivariate analyses of the relations between survival and age,
      sex, site of primary tumour, stage, and histopathological type were made using
      the log-rank test and Cox's regression analysis. Sex and age were not associated
      with survival. Treatment and stage of tumour at the time of diagnosis were
      related to survival. The overall survival rates were higher in patients with
      stages I or II cancer than those in stages III (OR=2.8, 95% CI=1.8 to 4.4) or IV
      (OR=4.6, 95% CI=3.1 to 6.8) at the time of diagnosis. Patients treated with
      radiotherapy had lower survival than those who had been operated on and had
      radiotherapy or operation alone (OR=2.8, 95% CI=1.7 to 4.5). There was no
      difference in survival depending on the histological type of tumour. To achieve
      higher survival, early detection and diagnosis of oral cancers should be
      emphasised in oral health programmes to improve public awareness and preventive
      activities among dentists in Iran.

PMID- 18096284
TI  - Endoscopically-assisted resection of a branchial cyst.

PMID- 18096285
TI  - Phytotoxicities of fluoranthene and phenanthrene deposited on needle surfaces of
      the evergreen conifer, Japanese red pine (Pinus densiflora Sieb. et Zucc.).
AB  - Polycyclic aromatic hydrocarbons (PAHs) have been widely studied with respect to
      their carcinogenic and mutagenic effects on animals and human cells. Phenanthrene
      (PHE) and fluoranthene (FLU) effects on the needle photosynthetic traits of 2
      year-old Japanese red pine (Pinus densiflora Sieb. et. Zucc.) seedlings were
      investigated. Three months after fumigation of foliage with solutions containing
      these PAHs (10 microM each), FLU had negative effects on net photosynthesis at
      near-saturating irradiance, stomatal conductance, initial chlorophyll
      fluorescence, and the contents of total chlorophyll, magnesium, and ribulose 1,5
      bisphosphate carboxylase (rubisco) of current-year needles. PHE had similar
      negative effects to FLU but in lesser magnitude. The effects of the PAHs were
      mitigated by the addition of an OH-radical scavenger (mannitol) into the PAH
      solutions. PAHs deposited on the surface of pine needles may induce the
      generation of reactive oxygen species in the photosynthetic apparatus, a manner
      closely resembling the action of the herbicide paraquat.

PMID- 18096286
TI  - Increased serum levels of CCL11/eotaxin in schizophrenia.
AB  - BACKGROUND: Inflammatory and immune alterations occur and may be relevant in
      patients with schizophrenia. Chemokines are a subgroup of cytokines that play a
      major role in the recruitment of determined subsets of leukocytes into tissues.
      To date no study has evaluated whether levels of chemokines are altered in
      patients with schizophrenia. OBJECTIVE: To evaluate serum levels of CC and CXC
      chemokines of schizophrenic patients and age- and gender-matched controls.
      METHODS: Forty male institutionalized schizophrenic patients (mean+/-SD age,
      52.3+/-9.9) and 20 asymptomatic matched controls were recruited for this study.
      Severity of symptoms was assessed using BPRS, PANSS and AIMS. All patients were
      under typical antipsychotic treatment. Serum concentrations of chemokines were
      measured by ELISA. RESULTS: There was no statistical difference in serum levels
      of CCL2, CCL3, CCL24, CXCL9 and CXCL10 between controls and patients. Serum
      levels of CCL11 were increased in schizophrenic patients when compared to
      controls. Serum levels of chemokines were not correlated with the length of
      disease or hospitalization and the severity of involuntary movements, positive
      and/or negative symptoms. CONCLUSION: CCL11 is a ligand for CCR3, a receptor
      expressed preferentially on Th2 lymphocytes, mast cells and eosinophils. Higher
      serum levels of CCL11 in schizophrenia reinforce the view that this disease may
      be associated with a Th1/Th2 imbalance with a shift toward a Th2 immune response.

PMID- 18096287
TI  - A placebo controlled study of the propentofylline added to risperidone in chronic
      schizophrenia.
AB  - Impaired activity of the purinergic system is a plausible common factor that
      could be responsible for many aspects of schizophrenia. Based on purinegic
      hypothesis of schizophrenia, pharmacological treatments enhancing adenosine
      activity could be effective treatment in schizophrenia. Propentofylline is a
      novel xantine derivative which is being developed for treatment of degenerative
      and vascular dementia. It enhances extracellular adenosine level via inhibition
      of adenosine uptake. The purpose of the present investigation was to assess the
      efficacy of propentofylline as an adjuvant agent in the treatment of chronic
      schizophrenia in an 8-week double blind and placebo controlled trial. Eligible
      participants in this study were 50 patients with chronic schizophrenia. All
      patients were inpatients and were in the active phase of the illness, and met DSM
      IV-TR criteria for schizophrenia. Patients were allocated in a random fashion, 25
      to risperidone 6 mg/day plus propentofylline 900 mg/day (300 mg TDS) and 25 to
      risperidone 6 mg/day plus placebo. The principal measure of the outcome was
      Positive and Negative Syndrome Scale (PANSS). Although both protocols
      significantly decreased the score of the positive, negative and general
      psychopathological symptoms over the trial period, the combination of risperidone
      and propentofylline showed a significant superiority over risperidone alone in
      the treatment of positive symptoms, general psychopathology symptoms as well as
      PANSS total scores. The means Extrapyramidal Symptoms Rating Scale for the
      placebo group were higher than in the propentofylline group over the trial.
      However, the differences were not significant. The present study indicates
      propentofylline as a potential adjunctive treatment strategy for chronic
      schizophrenia. Nevertheless, results of larger controlled trials are needed,
      before recommendation for a broad clinical application can be made.

PMID- 18096288
TI  - Beer consumption reduces cerebral oxidation caused by aluminum toxicity by
      normalizing gene expression of tumor necrotic factor alpha and several
      antioxidant enzymes.
AB  - Aluminum (Al)-induced neurotoxicity is well known and different salts of aluminum
      have been reported to accelerate oxidative damage to biomolecules. The present
      study has examined whether silicon consumed in the form of silicic acid or beer
      could potentially inhibit aluminum toxicity in the brain. Male mice were
      administered with Al(NO(3))(3) orally at a dose of 450 mg/kg/day in drinking
      water for 3 month. Experimental mice were given Al(NO(3))(3) along with 50 mg/L
      of silicic acid or with 0.5 ml/day of beer. Al brain levels in the Al group were
      four times higher than those of control mice while silicic acid and beer group
      values were 40% lower than those of the Al group. We have observed that beer
      prevented accumulation of lipid damage significantly, which resulted from
      aluminum intake. Decline in the expression of mRNA of endogenous antioxidant
      enzymes associated with aluminum administration was also inhibited by beer and
      silicic acid. The tumor necrosis factor alpha (TNFalpha) RNA expression was
      normalized in silicic acid and beer groups. Very high and significant
      correlations were found for the different parameters tested suggesting that
      moderate consumption of beer, due to its silicon content, effectively protects
      against the neurotoxic effects of aluminum.

PMID- 18096289
TI  - [30th Congress of the Group for Advancement of Microsurgery (GAM), "Le Bellevue"
      Congress Center, Biarritz, France, May 7-8, 2007].

PMID- 18096290
TI  - Determination of miosis threshold from whole-body vapor exposure to sarin in
      African green monkeys.
AB  - We determined the threshold concentration of sarin vapor exposure producing
      miosis in African green monkeys (Chlorocebus aethiops). Monkeys (n=8) were
      exposed to a single concentration of sarin (0.069-0.701mg/m3) for 10min. Changes
      in pupil size were measured from photographs taken before and after the exposure.
      Sarin EC50 values for miosis were determined to be 0.166mg/m3 when miosis was
      defined as a 50% reduction in pupil area and 0.469mg/m3 when miosis was defined
      as a 50% reduction in pupil diameter. Monkeys were also evaluated for behavioral
      changes from sarin exposure using a serial probe recognition test and performance
      remained essentially unchanged for all monkeys. None of the concentrations of
      sarin produced specific clinical signs of toxicity other than miosis. Sarin was
      regenerated from blood sampled following exposure in a concentration-dependent
      fashion. Consistent with a predominant inhibition of acetylcholinesterase (AChE),
      more sarin was consistently found in RBC fractions than in plasma fractions.
      Further, elimination of regenerated sarin from RBC fractions was slower than from
      plasma fractions. Blood samples following exposure also showed concentration
      dependent inhibition of AChE activity and, to a lesser extent,
      butyrylcholinesterase activity. At the largest exposure concentration, AChE
      inhibition was substantial, reducing activity to approximately 40% of baseline.
      The results characterize sarin exposure concentrations that produce miosis in a
      large primate species in the absence of other overt signs of toxicity. Further,
      these results extend previous studies indicating that miosis is a valid early
      indicator for the detection of sarin vapor exposure.

PMID- 18096291
TI  - Thermoregulation and its influence on toxicity assessment.
AB  - The thermoregulatory system of laboratory rodents is susceptible to a variety of
      chemical toxicants. Because temperature directly affects the reaction of
      virtually all biological processes, it is critical to consider how changes in the
      thermoregulatory response to a toxicant may affect physiological, behavioral, and
      pathological endpoints. Researchers in industry and government laboratories are
      often faced with addressing how changes in body temperature of their experimental
      subjects may affect the outcome of a particular toxicity test and/or screening
      panel. However, many toxicologists are either unaware of the importance or ignore
      the potential impact of a toxic-induced change in body temperature. This paper
      endeavors to summarize the importance of thermoregulation in the study of
      toxicology and propose recommendations for thermometry that researchers may
      utilize in their toxicological studies.

PMID- 18096292
TI  - Intra-arrest cooling with delayed reperfusion yields higher survival than earlier
      normothermic resuscitation in a mouse model of cardiac arrest.
AB  - BACKGROUND: Therapeutic hypothermia (TH) represents an important method to
      attenuate post-resuscitation injury after cardiac arrest. Laboratory
      investigations have suggested that induction of hypothermia before return of
      spontaneous circulation (ROSC) may confer the greatest benefit. We hypothesized
      that a short delay in resuscitation to induce hypothermia before ROSC, even at
      the expense of more prolonged ischemia, may yield both physiological and survival
      advantages. METHODS: Cardiac arrest was induced in C57BL/6 mice using intravenous
      potassium chloride; resuscitation was attempted with CPR and fluid
      administration. Animals were randomized into three groups (n=15 each): a
      normothermic control group, in which 8 min of arrest at 37 degrees C was followed
      by resuscitation; an early intra-arrest hypothermia group, in which 6.5 min of 37
      degrees C arrest were followed by 90s of cooling, with resuscitation attempted at
      30 degrees C (8 min total ischemia); and a delayed intra-arrest hypothermia
      group, with 90s cooling begun after 8 min of 37 degrees C ischemia, so that
      animals underwent resuscitation at 9.5 min. RESULTS: Animals treated with TH
      demonstrated improved hemodynamic variables and survival compared to normothermic
      controls. This was the case even when comparing the delayed intra-arrest
      hypothermia group with prolonged ischemia time against normothermic controls with
      shorter ischemia time (7-day survival, 4/15 vs. 0/15, p<0.001). CONCLUSIONS:
      Short resuscitation delays to allow establishment of hypothermia before ROSC
      appear beneficial to both cardiac function and survival. This finding supports
      the concept that post-resuscitation injury processes begin immediately after
      ROSC, and that intra-arrest cooling may serve as a useful therapeutic approach to
      improve survival.

PMID- 18096294
TI  - Effects of varying stop-signal probability on ERPs in the stop-signal task: do
      they reflect variations in inhibitory processing or simply novelty effects?
AB  - The aim of the present study was to determine whether ERP modulations associated
      with varying the probability of the stop-signal in the stop-signal task reflect
      variations in inhibitory processing, or whether they simply reflect general
      arousal associated with novel stimuli. This was achieved by examining the effects
      of probability on a control "ignore-signal" stimulus in addition to the stop
      signal. ERP findings revealed large fronto-central N1 and P3 components that were
      larger in amplitude for stop-signals than ignore-signals, and when stimuli were
      rare (30%) compared to frequent (70%). However, probability effects were not
      greater for stop-signals compared to ignore-signals, discounting an
      interpretation exclusively in line with inhibitory processing. A principal
      components analysis (PCA) revealed a slow-wave ERP component that partially
      accounted for these probability effects. Together, the present findings indicate
      that ERP differences between rare and frequent stop-signals did not primarily
      reflect varying inhibitory requirements, but rather may be confounded by novelty
      effects.

PMID- 18096293
TI  - Laboratory-based blood pressure recovery is a predictor of ambulatory blood
      pressure.
AB  - The recovery phase of the stress response is an individual difference
      characteristic that may predict cardiovascular risk. The purpose of this study
      was to examine whether laboratory-based blood pressure (BP) recovery predicts
      ambulatory BP (ABP). One hundred and eighty-two participants underwent a standard
      laboratory stress protocol, involving a 20-min baseline rest period, and four
      stressors presented in a counterbalanced order, each followed by a 10-min
      recovery period. Participants also wore an ABP monitor for 24h during a typical
      workday. Hierarchical regression analyses showed that BP recovery accounted for
      significant additional variance for daytime SBP (p<0.001), nighttime SBP
      (p<0.001), daytime DBP (p<0.001), and nighttime DBP (p<0.001), after controlling
      for baseline and reactivity BP. Results suggest that persistence of the BP
      response following stress may be a more salient characteristic of the stress
      response in understanding its potential impact on longer term cardiovascular
      regulation.

PMID- 18096295
TI  - Assessment of the predictive value of serum progesterone levels on early
      pregnancy prognosis in spontaneous twin gestations: a prospective study.
AB  - OBJECTIVES: The aim of this study was to assess the predictive value of serum
      progesterone levels in early pregnancy prognosis in spontaneous dichorionic
      diamniotic twin gestations. STUDY DESIGN: This study was carried out among 38
      spontaneous dichorionic-diamniotic twin gestations between January 2003 and June
      2005 in the Department of Obstetrics and Gynaecology at the Gulhane Military
      Medical Academy. Serum progesterone levels were measured at 7 and 10 weeks'
      gestation and pregnancies were followed until 14 gestational weeks by ultrasound
      examination. RESULTS: We found that a progesterone level of 58 nmol/l in the 7th
      gestational week and of 51 ng/ml at 10 gestational weeks has a predictive value
      for viable intrauterine twin pregnancies with 83% sensitivity and 69% specificity
      and 83% sensitivity and 84% specificity, respectively. CONCLUSION: Progesterone
      levels in the early gestational weeks may be a biochemical marker for the
      prediction of a twin pregnancy outcome and may reduce the number of ultrasound
      examinations.

PMID- 18096296
TI  - Acute pancreatitis in pregnancy: place of the different explorations (magnetic
      resonance cholangiopancreatography, endoscopic ultrasonography) and their
      therapeutic consequences.

PMID- 18096298
TI  - Treatment of low-strength soluble wastewater using an anaerobic baffled reactor
      (ABR).
AB  - Treatment of low-strength soluble wastewater (COD approximately 500 mg/L) was
      studied using an eight chambered anaerobic baffled reactor (ABR). At pseudo
      steady-state (PSS), the average total and soluble COD values (COD(T) and COD(S))
      at 8h hydraulic retention time (HRT) were found to be around 50 and 40 mg/L,
      respectively, while at 10h HRT average COD(T) and COD(S) values were of the order
      of 47 and 37 mg/L, respectively. COD and BOD (3 day, 27 degrees C) removal
      averaged more than 90%. Effluent conformed to Indian standards laid down for BOD
      (less than 30 mg/L). Reactor effluent characteristics exhibited very low values
      of standard deviation indicating excellent reactor stability at PSS in terms of
      effluent characteristics. Based on mass balance calculations, more than 60% of
      raw wastewater COD was estimated to be recovered as CH(4) in the gas phase.
      Compartment-wise profiles indicated that most of the BOD and COD got reduced in
      the initial compartments only. Sudden drop in pH (7.8-6.7) and formation of
      volatile fatty acids (VFA) (53-85 mg/L) were observed in the first compartment
      due to acidogenesis and acetogenesis. The pH increased and VFA concentration
      decreased longitudinally down the reactor. Residence time distribution (RTD)
      studies revealed that the flow pattern in the ABR was neither completely plug
      flow nor perfectly mixed. Observations from scanning electron micrographs (SEM)
      suggest that distinct phase separation takes place in an ABR.

PMID- 18096299
TI  - An inexact dynamic optimization model for municipal solid waste management in
      association with greenhouse gas emission control.
AB  - Municipal solid waste (MSW) should be properly disposed in order to help protect
      environmental quality and human health, as well as to preserve natural resources.
      During MSW disposal processes, a large amount of greenhouse gas (GHG) is emitted,
      leading to a significant impact on climate change. In this study, an inexact
      dynamic optimization model (IDOM) is developed for MSW-management systems under
      uncertainty. It grounds upon conventional mixed-integer linear programming (MILP)
      approaches, and integrates GHG components into the modeling framework. Compared
      with the existing models, IDOM can not only deal with the complex tradeoff
      between system cost minimization and GHG-emission mitigation, but also provide
      optimal allocation strategies under various emission-control standards. A case
      study is then provided for demonstrating applicability of the developed model.
      The results indicate that desired waste-flow patterns with a minimized system
      cost and GHG-emission amount can be obtained. Of more importance, the IDOM
      solution is associated with over 5.5 million tonnes of TEC reduction, which is of
      significant economic implication for real implementations. Therefore, the
      proposed model could be regarded as a useful tool for realizing comprehensive MSW
      management with regard to mitigating climate-change impacts.

PMID- 18096300
TI  - Characteristics and significance of liquid effluent from woodchip corrals in
      Scotland.
AB  - Woodchip corrals are increasingly used as cost effective means of over-wintering
      livestock in temperate regions but there is little information on their potential
      environmental impact. Four woodchip corrals of varying characteristics were
      instrumented to capture and quantify the flows reaching the base, where pollutant
      fluxes may move either vertically to groundwater, or laterally to a water course.
      Samples for chemical analysis were collected daily by auto-sampler. Samples for
      bacterial analysis were aseptically hand-sampled. Sampling frequency was
      increased during high flow events and sampling was conducted over a 12-month
      period. Microbiological samples were analysed for total coliform (TC),
      presumptive Escherichia coli (EC) and intestinal enterococci (IE). Leachate was
      also analysed for total phosphorus, phosphate, total nitrogen, ammonium, total
      oxidised nitrogen, nitrite and nitrate. Each corral had a recording rain gauge
      sited within 10 m of the corral surface. Mean total nitrogen concentration in
      leachate was 339.5 mg l(-1), of which ammoniacal-N comprised approximately 57%.
      Mean total phosphorus concentration was 94.7 mg l(-1). Geometric mean
      concentrations of TC, EC and IE were 95,461, 94,983 and 55,552 cfu100 ml(-1),
      respectively. Significant flows of leachate occurred at the base of the corrals
      on most days during the 1-year sampling period and flow rate increased with
      stocking density. Strong positive linear relationships were found between the
      concentrations of the nutrient parameters and discharge. Strong positive
      curvilinear relations were found between faecal indicator concentrations and
      discharge. Different relationships were observed in the stocked and unstocked
      corrals. The resulting fluxes are sufficient to give concern and to indicate that
      corral development is worthy of regulatory attention.

PMID- 18096301
TI  - End-diastolic block in cerebral circulation may predict intraventricular
      hemorrhage in hypotensive extremely-low-birth-weight infants.
AB  - We investigated the association of intracranial arterial end-diastolic block with
      mean arterial pressure (MAP), patent ductus arteriosus (PDA) and intraventricular
      hemorrhage (IVH) in infants with birth weights <1000 g. End-diastolic block was
      diagnosed when end-diastolic flow was found to be absent from the Doppler
      waveforms in cerebral arteries by pulsed Doppler ultrasound examinations. Cranial
      ultrasonography and pulsed Doppler examination of anterior cerebral and basilar
      arteries were performed in 55 preterm infants (gestational age range 24-31 wk)
      one to four times during the first four days of life. Of these, 22 (40%)
      developed an end-diastolic block at least once (block group); in 33 no block was
      detected (control group). Echocardiography was performed and MAP recorded
      concomitantly. The block group infants had significantly lower mean MAPs than the
      controls and 59% of those had MAP of 30 mm Hg or lower. In the block group, IVH
      developed more often in infants with MAP <30 mm Hg (46%) than in infants with
      MAPs >30 mm Hg (0%). However, in the control group IVH developed equally
      frequently in infants with MAP < or =30 mm Hg (33%) and in infants with MAP >30
      mm Hg (30%). PDA was a significant risk factor for IVH. An end-diastolic block in
      the cerebral circulation, together with a MAP of < or =30 mm Hg or less and the
      presence of PDA during the first four days of life, might be associated with IVH
      in extremely-low-birth-weight infants.

PMID- 18096303
TI  - Evaluating tissue changes with ultrasound during radiofrequency ablation.
AB  - The purpose of this study was to estimate tissue changes during radiofrequency
      (RF) ablation by correlating echo frequency shifts and temperature elevations.
      Experiments were performed on phantoms (tissue mimicking gel) and in-vitro turkey
      breast. Heating was performed with a modified RF-ablation system. Intermittent RF
      was applied and the temperature at the electrode tip was continually measured by
      an embedded thermocouple. Various voltages (10-30V) were applied to achieve a
      wide range of temperature elevations between 10 and 80 degrees C and ablation
      sizes between 5 and 27 mm in width. B-mode images and raw data were acquired
      every 5 s by a modified ultrasound imaging system. The raw data from each line
      and frame was processed using an algorithm to measure spectral shifts of the echo
      signals in the power spectrum. The phantom experiments showed positive frequency
      shifts as the temperature rose, with dependency on the heating rate. A linear
      relationship (R(2) > 0.96) was found between the RF-applied voltage and the width
      of the heated area, defined by frequency changes larger than 0.05 MHz. In-vitro
      experiments showed a correlation (R(2) = 0.84) between the width of the
      coagulated area and the maximal width of the region with more than 0.12 MHz
      frequency shifts, but a lower correlation (R(2) = 0.4) between the width of the
      coagulated area and the temperature elevation. In conclusion, correlation was
      found between echo frequency shifts and temperature elevations and between echo
      frequency shifts and the width of the ablated area during intermittent RF
      ablation. Our results suggest that, with further refinement and validation,
      ultrasound could be used to measure RF heating and its induced coagulation.

PMID- 18096302
TI  - Herpes simplex virus thymidine kinase-mediated suicide gene therapy using
      nano/microbubbles and ultrasound.
AB  - A physical method using ultrasound (US) and nano/microbubbles (NBs) can deliver
      exogenous molecules noninvasively into a specific target site. In this study, we
      evaluated the application of this technology to cancer gene therapy using prodrug
      activation therapy. Low-intensity pulsed ultrasound (1 MHz; 1.3 W/cm(2)) and NBs
      were used to transduce the herpes simplex thymidine kinase (HSVtk) gene in vitro,
      leading to gene transfer. The addition of ganciclovir (GCV) to the transduced
      cells led to HSVtk/GCV-dependent cell death mediated by apoptosis. This
      technology was then assessed in vivo, using mice bearing subcutaneous tumors (1
      MHz; 3.0 W/cm(2)). Gene transfer to the tumor, measured by luciferase activity,
      was transient, with a peak of expression 24 h after transduction, and decreased
      at 48 h, demonstrating the transient nature of US/NB-mediated gene transfer. The
      therapeutic potential of this approach was evaluated through repeated
      intratumoral gene delivery using US/NB-mediated transfer of the HSVtk gene,
      followed by recurrent administration of GCV, using two different experimental
      treatment protocols. In both cases, dramatic reductions of the tumor size by a
      factor of four were observed. Altogether, these data demonstrate the potential of
      US/NB as a new physical gene delivery method for cancer gene therapy. (E-mail:
      kodama@tubero.tohoku.ac.jp).

PMID- 18096304
TI  - Pharmacokinetics of perfluorobutane following intravenous bolus injection and
      continuous infusion of sonazoid in healthy volunteers and in patients with
      reduced pulmonary diffusing capacity.
AB  - The ultrasound contrast agent Sonazoidtrade mark was administered as an i.v.
      bolus injection of 0.6 microL microbubbles/kg body weight or as a continuous
      infusion over 30 min at a rate of 1.2 microL microbubbles/kg body weight to
      healthy volunteers and patients with reduced pulmonary diffusing capacity.
      Expired air and blood samples were collected from 32 subjects and perfluorobutane
      (PFB) gas was analyzed using validated gas chromatography mass spectrometry
      methods. Blood concentrations of PFB declined biphasicly with a distribution half
      life (t(0.5 to 15)) of 2 to 3 min and an elimination half-life (t(15 to 120)) of
      30 to 45 min. Area under the curve (AUC) values in patients with impaired gas
      diffusion were significantly larger than those in healthy volunteers. The
      exhalation kinetics were somewhat variable with a PFB elimination half-life (t(15
      to 120)) of 28 to 111 min. Clearance of PFB was independent of study population
      and mode of administration. There were no deaths and no serious adverse events
      that resulted in the withdrawal of a subject from the study. With the exception
      that arthralgia predominated in healthy volunteers, healthy volunteers and
      diseased subjects did not show a different adverse event profile whether Sonazoid
      was administered as a bolus injection or as an infusion. Assessment of laboratory
      parameters (serum biochemistry, haematology and urinalysis), vital signs, oxygen
      saturation and electrocardiograms (ECGs) showed no changes which caused safety
      concern. (E-mail: Kristin.Landmark@ge.com).

PMID- 18096305
TI  - Modeling envelope statistics of blood and myocardium for segmentation of
      echocardiographic images.
AB  - The objective of this study was to investigate the use of speckle statistics as a
      preprocessing step for segmentation of the myocardium in echocardiographic
      images. Three-dimensional (3D) and biplane image sequences of the left ventricle
      of two healthy children and one dog (beagle) were acquired. Pixel-based speckle
      statistics of manually segmented blood and myocardial regions were investigated
      by fitting various probability density functions (pdf). The statistics of heart
      muscle and blood could both be optimally modeled by a K-pdf or Gamma-pdf
      (Kolmogorov-Smirnov goodness-of-fit test). Scale and shape parameters of both
      distributions could differentiate between blood and myocardium. Local estimation
      of these parameters was used to obtain parametric images, where window size was
      related to speckle size (5 x 2 speckles). Moment-based and maximum-likelihood
      estimators were used. Scale parameters were still able to differentiate blood
      from myocardium; however, smoothing of edges of anatomical structures occurred.
      Estimation of the shape parameter required a larger window size, leading to
      unacceptable blurring. Using these parameters as an input for segmentation
      resulted in unreliable segmentation. Adaptive mean squares filtering was then
      introduced using the moment-based scale parameter (sigma(2)/mu) of the Gamma-pdf
      to automatically steer the two-dimensional (2D) local filtering process. This
      method adequately preserved sharpness of the edges. In conclusion, a trade-off
      between preservation of sharpness of edges and goodness-of-fit when estimating
      local shape and scale parameters is evident for parametric images. For this
      reason, adaptive filtering outperforms parametric imaging for the segmentation of
      echocardiographic images.

PMID- 18096306
TI  - Editorial comment on: photodynamic diagnosis in urology: state-of-the-art.

PMID- 18096307
TI  - Photodynamic diagnosis in urology: state-of-the-art.
AB  - OBJECTIVES: To provide an overview on the methodology and clinical relevance of
      fluorescence diagnosis with exogenous fluorochromes or fluorochrome prodrugs in
      urology. METHODS: The methodology is summarised on the basis of our experience
      and the relevant literature. Clinical results and perspectives are reported and
      concluded after we scanned and evaluated sources from PubMed. Search items were
      "aminolev*" or "hypericin" or "photodyn*" or "porphyrin" or "fluorescence" or
      "autofluorescence" and "bladder" or "prostate" or "kidney" or "peni*" or
      "condylo*". Some literature was also obtained from journals not indexed. RESULTS:
      A large number of clinical trials have shown that photodynamic diagnosis (PDD)
      improves the ability to detect inconspicuous urothelial carcinoma of the bladder.
      Fluorescence diagnosis has recently been approved in Europe for the detection of
      bladder cancer after instillation of a hexaminolevulinate (Hexvix) solution. PDD
      is recommended by the European Association of Urology for the diagnosis of
      carcinoma in situ of the bladder. To date, the major weakness of PDD for the
      detection of bladder cancer is its relatively low specificity. Initial results
      with PDD for the detection of penile carcinoma, prostate cancer, kidney tumours,
      and urethral condylomata are promising. CONCLUSIONS: To determine the actual
      impact of PDD on recurrence and progression rates of bladder cancer, further long
      term observational studies are necessary. These studies also will clarify whether
      PDD is cost efficient.

PMID- 18096308
TI  - Editorial comment on: photodynamic diagnosis in urology: state-of-the-art.

PMID- 18096309
TI  - Response of follicle cells to ovulatory stimuli within the follicle and in
      primary culture.
AB  - Cultures of mural granulosa cells (mGCs) and cumulus oocyte complexes (COCs) were
      employed to investigate various aspects of follicle cell function and response to
      gonadotropins. Yet, such studies do not reveal the intricate cell-to-cell
      interactions in the whole follicle. Here we compare the ovulatory responses to
      LH/hCG or epiregulin (ER) of rat preovulatory follicles and of mGC and COC
      whether they were stimulated within the follicle or in primary cell cultures. The
      expression of TSG-6 and COX-2 mRNA varied according to the culture system and
      mode of stimulation. In primary cultures stimulated with LH or ER resulted in
      their lower expression as compared to stimulation of follicles. LH/hCG stimulated
      higher follicular and mGC AR, ER and EGFR mRNA levels than in primary mGC
      cultures. COCs stimulated by LH/hCG in vivo responded with AR, ER and EGFR mRNA
      expression, but not in culture where only EGFR mRNA was stimulated. The
      differences in gene expression of mGCs and COCs when stimulated within their
      intact follicle or in primary cultures revealed here underscore the important
      role of cell-cell interactions in follicle physiology. Therefore, results
      obtained in primary mGC cultures need careful validation in models reproducing
      such in situ interactions for revealing mGC activity within the intact follicle.

PMID- 18096311
TI  - Left thalamomegaly in a patient with partial epilepsy.
AB  - Temporal lobe epilepsy (TLE) is associated with modification in thalamic
      structure and function. In particular, thalamic atrophy and hypometabolism can
      occur, affecting ipsilateral, contralateral thalami or both. We describe a 28
      year-old epileptic woman, who presented peculiar neuroimaging findings, with
      enlargement of the thalamus contralateral to the epileptic focus. The patient was
      born from dystocic delivery, she presented partial motor seizures in the left
      side of the body, followed by generalisation, and the EEG showed a right temporal
      epileptic focus. Serial CT and MRI scan, performed along 11 years, showed a non
      evolutive left thalamomegaly. 18-FDG PET showed reduced metabolic activity in the
      upper right temporal gyrus and in the ipsilateral thalamus. Thalamic asymmetry in
      our patient could be an occasional finding.

PMID- 18096310
TI  - Activated glucocorticoid receptor interacts with the INHAT component Set/TAF
      Ibeta and releases it from a glucocorticoid-responsive gene promoter, relieving
      repression: implications for the pathogenesis of glucocorticoid resistance in
      acute undifferentiated leukemia with Set-Can translocation.
AB  - Set/template-activating factor (TAF)-Ibeta, part of the Set-Can oncogene product
      found in acute undifferentiated leukemia, is a component of the inhibitor of
      acetyltransferases (INHAT) complex. Set/TAF-Ibeta interacted with the DNA-binding
      domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and
      repressed GR-induced transcriptional activity of a chromatin-integrated
      glucocorticoid-responsive and a natural promoter. Set/TAF-Ibeta was co
      precipitated with glucocorticoid response elements (GREs) of these promoters in
      the absence of dexamethasone, while addition of the hormone caused dissociation
      of Set/TAF-Ibeta from and attraction of the p160-type coactivator GRIP1 to the
      promoter GREs. Set-Can fusion protein, on the other hand, did not interact with
      GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced
      enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF
      Ibeta acts as a ligand-activated GR-responsive transcriptional repressor, while
      Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly
      contributing to the poor responsiveness of Set-Can-harboring leukemic cells to
      glucocorticoids.

PMID- 18096312
TI  - Androgen manipulation alters oxidative DNA adduct levels in androgen-sensitive
      prostate cancer cells grown in vitro and in vivo.
AB  - Intracellular reactive oxygen species (ROS) may cause oxidative DNA damage,
      resulting in the formation of adducts such as 8-oxo-7,8-dihydro-2'-deoxyguanosine
      (8-oxo-dG) and the cyclic pyrimidopurinone N-1, N(2) malondialdehyde-2'
      deoxyguanosine (M(1)dG). These adducts have been associated with carcinogenesis,
      genomic instability and clonal evolution. We tested two hypotheses in human
      prostate cancer cells grown in vitro and in a xenograft model: (1) treatment of
      androgen-sensitive cells with DHT increases levels of oxidative DNA adduct
      levels; (2) flutamide, a competitive androgen receptor antagonist, prevents DHT
      induced changes. Levels of M(1)dG and 8-oxo-dG adducts were determined by
      immunoslot blot and liquid chromatography-tandem mass spectrometry. M(1)dG and 8
      oxo-dG levels were significantly higher than control levels in LNCaP cells
      exposed to supra-physiological concentrations (25-100 nM) of DHT (both P<0.05 by
      ANOVA). Flutamide pre-treatment completely prevented this increase. In the
      xenograft model, tumour levels of M(1)dG were decreased by 46% (P=0.001 by Mann
      Whitney Test) in flutamide-treated animals compared to controls. The changes
      demonstrated suggest that oxidative DNA adducts may serve as biomarkers of the
      efficacy of androgen manipulation in chemoprevention trials.

PMID- 18096313
TI  - Trastuzumab decreases the number of circulating and disseminated tumor cells
      despite trastuzumab resistance of the primary tumor.
AB  - We have recently shown that despite of the fact that the ErbB2-positive JIMT-1
      human breast cancer cells intrinsically resistant to trastuzumab in vitro,
      trastuzumab inhibited the outgrowth of early phase JIMT-1 xenografts in SCID mice
      via antibody-dependent cellular cytotoxicity (ADCC). Here we show that
      trastuzumab significantly reduces the number of circulating and disseminated
      tumor cells (CTCs and DTCs) in this xenograft model system at a time when the
      primary tumor is already unresponsive to trastuzumab. This observation suggests
      that ErbB2 positive CTCs and DTCs might be sensitive to trastuzumab-mediated ADCC
      even if when the primary tumor is already non-responsive. Thus, trastuzumab
      treatment might also be beneficial in the case of patients with breast cancer
      that is already trastuzumab resistant.

PMID- 18096314
TI  - Combination gene therapy using multidrug resistance (MDR1) gene shRNA and herpes
      simplex virus-thymidine kinase.
AB  - The current study was designed to evaluate the anti-tumor effects of MDR1 shRNA
      in combination with herpes simplex virus-thymidine kinase/ganciclovir (HSV
      tk/GCV) suicide gene therapy system. Introduction of an MDR1-targeted small
      hairpin RNA (shMDR) markedly enhanced the intracellular accumulation of and
      increased sensitivity to drugs transported by P-glycoprotein. Functional TK-eGFP
      fusion protein expression was confirmed by Western blot analysis and ganciclovir
      uptake assay. Compared with GCV or doxorubicin alone, the combination of anti
      cancer drug chemotherapy with GCV administration displays additive cytotoxicity
      in shMDR1-TK-eGFP expressing cells. These results for the first time suggest the
      potential of combination gene therapy using suicide gene therapy and RNAi-based
      gene therapy in vitro.

PMID- 18096316
TI  - Floods from tailings dam failures.
AB  - This paper compiles the available information on historic tailings dam failures
      with the purpose to establish simple correlations between tailings ponds
      geometric parameters (e.g., dam height, tailings volume) and the hydraulic
      characteristics of floods resulting from released tailings. Following the
      collapse of a mining waste dam, only a part of tailings and polluted water stored
      at the dam is released, and this outflow volume is difficult to estimate prior
      the incident. In this study, tailings' volume stored at the time of failure was
      shown to have a good correlation (r2=0.86) with the tailings outflow volume, and
      the volume of spilled tailings was correlated with its run-out distance
      (r2=0.57). An envelope curve was drawn encompassing the majority of data points
      indicating the potential maximum downstream distance affected by a tailings'
      spill. The application of the described regression equations for prediction
      purposes needs to be treated with caution and with support of on-site measurement
      and observations. However, they may provide a universal baseline approximation on
      tailing outflow characteristics (even if detailed dam information is
      unavailable), which is of a great importance for risk analysis purposes.

PMID- 18096315
TI  - Antitumor activity of G-quadruplex-interactive agent TMPyP4 in K562 leukemic
      cells.
AB  - The cationic porphyrin TMPyP4 can bind to and stabilize DNA guanine-quadruplexes.
      We investigated the molecular mechanism of the antitumor activity of TMPyP4 in
      K562 cells and human telomere reverse transcriptase subunit (hTERT)-transfected
      K562 cells in which telomerase activity, followed by telomere elongation, was
      enhanced. Treatment with 100 microM TMPyP4 significantly inhibited the growth of
      both types of cell, with decreases of cells in the G(1) phase and increases of
      those in the S and G(2)/M phases after 48 h, preceding cell death after 72 h.
      cDNA microarray analysis revealed upregulation of 33 genes and downregulation of
      54 genes in K562 cells treated with 100 microM TMPyP4 for 48 h. Moreover, TMPyP4
      decreased c-Myc protein expression, increased the expression of p21(CIP1) and
      p57(KIP2) proteins, and activated p38 mitogen-activated protein kinase, c-Jun N
      terminal kinase, and extracellular signal-regulated kinase. These findings may
      provide a rationale for the development of guanine-quadruplex-interactive agents
      as novel antileukemic therapies.

PMID- 18096317
TI  - Mineralogy, petrology, and chemistry studies to evaluate oxide copper ores for
      heap leaching in Sarcheshmeh copper mine, Kerman, Iran.
AB  - In recent years, as a result of biological, environmental, and economic
      considerations, available copper in copper oxide ores that could not be recovered
      by pyrometallurgical methods was accumulated in so-called oxide dumps. Suitable
      material is treated with dilute sulfuric acid in a heap-leaching process,
      whereupon the copper content of the rock slowly dissolves in the acidic solution.
      The performed investigations show that one needs to consider the action of the
      acid on the copper oxide-containing rocks at the microscopic level. In this
      paper, we describe research carried out on oxide samples from the western dump of
      the Sarcheshmeh copper mine. Each sample was split into two parts and a portion
      of each was exposed to heap-leaching conditions in a column. Subsequently,
      polished sections, thin sections, and powdered samples were subjected to chemical
      analysis as well as petrographic and mineralogical considerations. Changes in the
      weight percentages of non-metal and metal minerals before and after acid
      treatment were measured. Microscopic studies have indicated that chemical
      analyses do not provide a complete picture of the effects of acid on the rock.
      Thus, microscopic studies on sections are shown to be a necessary requirement,
      neglection of which can have negative economic and environmental effects.

PMID- 18096318
TI  - Correlation of epidermal nerve fiber density with pain-related evoked potentials
      in HIV neuropathy.
AB  - HIV associated sensory neuropathy is a common neurological disorder with reported
      prevalence of 53%. When only small fibers are involved, the diagnosis of
      neuropathy remains difficult since standard nerve conduction studies generally
      are unremarkable. We assessed a method to identify small-fiber neuropathy using
      electrically evoked pain-related potentials and correlated the
      electrophysiological results with intraepidermal nerve fiber density in patients
      with HIV associated sensory neuropathy. Nineteen HIV positive patients were
      investigated for clinically diagnosed peripheral neuropathy with Neuropathy
      Symptoms Score (NSS)3 and Neuropathy Disability Score (NDS)5. Nine healthy HIV
      negative control subjects were recruited. We performed standard nerve conduction
      testing, electrically evoked pain-related potentials and skin biopsy in all
      participants. Pain-related evoked potentials revealed abnormalities in all HIV
      positive neuropathy patients, while standard nerve conduction testing was
      abnormal in eight patients only. Pain-related evoked potential latencies and
      amplitudes strongly correlated with intraepidermal nerve fiber density. The
      method of pain-related evoked potential conduction appears to be a sensitive,
      fast, non-invasive technique for the detection of small-fiber neuropathy and may
      prove to become a valuable diagnostic asset.

PMID- 18096319
TI  - First isolate of Toxoplasma gondii from arctic fox (Vulpes lagopus) from
      Svalbard.
AB  - Cats are considered essential for the maintenance of Toxoplasma gondii in nature.
      However, T. gondii infection has been reported in arctic fox (Vulpes lagopus)
      from the Svalbard high arctic archipelago where felids are virtually absent. To
      identify the potential source of T. gondii, we attempted to isolate and
      genetically characterize the parasite from arctic foxes in Svalbard. Eleven foxes
      were trapped live in Grumant (78 degrees 11'N, 15 degrees 09'E), Svalbard, in
      September 2005 and 2006. One of the foxes was found to be seropositive to T.
      gondii by the modified agglutination test (MAT). The fox was euthanized and its
      heart and brain were bioassayed in mice for the isolation of T. gondii. All 10
      mice inoculated with brain tissue and one of the five inoculated with heart
      developed MAT antibodies, and tissue cysts were found in the brains of
      seropositive mice. Two cats fed tissues from infected mice shed T. gondii
      oocysts. Genotyping using 10 PCR-RFLP markers and DNA sequencing of gene loci
      BSR4, GRA6, UPRT1 and UPRT2 determined the isolate to be Type II strain, the
      predominant T. gondii lineage in the world.

PMID- 18096320
TI  - Dynamics of Eimeria oocyst excretion in dairy calves in the Province of Buenos
      Aires (Argentina), during their first 2 months of age.
AB  - Clinical coccidiosis is associated with high fecal contamination and stress
      situations, mainly in animals under 1 year of age. Artificially fed dairy calves
      are one of the categories most prone to suffer from this parasitic disease. The
      study was carried out in a commercial dairy farm. Feces samples of heifer calves
      between 2 and 8 weeks old were taken monthly for oocyst counts and Eimeria spp.
      identification. Of the 862 feces samples analyzed, 48% presented oocysts. When
      grouping the results of monthly samplings of each age group, it was observed that
      this percentage increased in the group of calves between 20 and 40 days of life,
      reaching the peak average of 85% of infection prevalence in the group with
      between 26 and 30 days of age. The discharge of oocysts observed between 21 and
      35 days of age was superior to the rest (p<0.05). This trend appeared every month
      throughout the whole year. However, during March, April, June, September and
      November, the curves in the group categories were higher than in the remaining
      months (p<0.05). Twelve Eimeria species were identified, being E. ellipsoidalis,
      E. bovis, E. zuernii and E. auburnensis those in highest numbers. E.
      ellipsoidalis had an important predominance in the opg composition, >75% up to 25
      days of life (p<0.05). E. bovis reached peak values in the 26 and 30 days group
      (p<0.05), remaining without significant variations in the last stage of the
      artificial milk feeding period (approximately 60 days of life), when the oocyst
      counts were significantly low. Oocysts of E. auburnensis appeared in great
      proportion (46%) in the cultures later than the previous species (p<0.05), in
      calves of the age groups of between 46 and 50 days of age. Oocysts of E. zuernii
      showed no trend associated with age. The highest prevalence of infection and of
      oocyst values appeared during the periods with better environmental conditions
      for sporulation, survival and dispersion of oocysts (spring and autumn),
      coincident with the highest birth rates and an elevated number of calves in the
      paddock. Calves developed a process of natural "vaccination" against coccidiosis.
      This was demonstrated by the decrease in the quantity of animals shedding oocysts
      and in the number of oocysts eliminated at the end of the artificial milk feeding
      period.

PMID- 18096322
TI  - Diminished cortisol responses to psychosocial stress associated with lifetime
      adverse events a study among healthy young subjects.
AB  - BACKGROUND: Animal and human studies have found that prior stressful events can
      result in an altered reactivity in the HPA axis. The aim of the present study was
      to investigate the role of adverse events in childhood on cortisol reactivity to
      psychosocial stress in young healthy subjects (n=80). METHODS: Salivary cortisol
      levels were measured before, during and after exposure to a psychosocial stress
      task in healthy men and women with high (n=33) and low (n=47) exposure to adverse
      childhood events. RESULTS: A significant blunted cortisol response was found in
      individuals with a history of adverse events compared to individuals with no
      adverse life events, with no differences in baseline cortisol levels. This
      finding appeared to be primarily driven by men. The groups did not differ on any
      other physiological or subjective stress measure, including heart rate, blood
      pressure, and subjective tension. CONCLUSIONS: These findings suggest that, at
      least in healthy young males, adverse childhood events are associated with
      changes in HPA-axis functioning. Longitudinal studies are needed to investigate
      whether the blunted cortisol response is a risk factor in the etiology of
      psychiatric disorders or rather reflects resiliency with regard to the
      development of psychopathology.

PMID- 18096321
TI  - Differential hypothalamic-pituitary-adrenal activation of the neuroactive
      steroids pregnenolone sulfate and deoxycorticosterone in healthy controls and
      alcohol-dependent subjects.
AB  - Ethanol and the neuroactive steroids have interactive neuropharmacological
      effects and chronic ethanol administration blunts the ethanol-induced increase in
      neuroactive steroid levels in rodent plasma and brain. Few studies have explored
      neuroactive steroid regulation in alcohol-dependent human subjects. In fact, the
      regulation of adrenal neuroactive steroids has not been well defined in healthy
      controls. We thus explored the regulation of two neuroactive steroids,
      pregnenolone sulfate (PREG-S) and deoxycorticosterone, by pharmacological
      challenges to the hypothalamic-pituitary-adrenal (HPA) axis in healthy controls
      and 1-month abstinent alcohol-dependent patients with co-occurring nicotine
      dependence. Plasma levels of PREG-S and deoxycorticosterone were measured by
      radioimmunoassay in controls and alcohol-dependent patients after challenges of
      naloxone, ovine corticotrophin releasing hormone (oCRH), dexamethasone,
      cosyntropin, and cosyntropin following high-dose dexamethasone. In addition,
      basal diurnal measures of both hormones were obtained. PREG-S plasma levels in
      healthy controls were increased by cosyntropin challenge (with and without
      dexamethasone pretreatment) and decreased by dexamethasone challenge. However,
      PREG-S concentrations were not altered by naloxone or oCRH challenges, suggesting
      that PREG-S is not solely regulated by hypothalamic or pituitary stimulation.
      Deoxycorticosterone, in contrast, is regulated by HPA challenge stimulation in a
      manner similar to cortisol. Alcohol-dependent patients had a blunted PREG-S
      response to cosyntropin (with and without dexamethasone pretreatment).
      Furthermore, the time to peak deoxycorticosterone response following oCRH was
      delayed in alcohol-dependent patients compared to controls. These results
      indicate that plasma PREG-S and deoxycorticosterone levels are differentially
      regulated by HPA axis modulation in human plasma. Further, alcohol-dependent
      patients show a blunted PREG-S response to adrenal stimulation and a delayed
      deoxycorticosterone response to oCRH challenge.

PMID- 18096323
TI  - Spinal balloon nucleoplasty: a hypothetical minimally invasive treatment for
      herniated nucleus pulposus.
AB  - Low back pain is the most common cause of disability under the age of 45. The
      annual incidence of back pain is estimated to be 5% and the lifetime prevalence
      is 80%. Majority of the patients with persistent symptoms are suffering from
      radiculopathy that is mainly caused by a herniated nucleus pulposus (HNP). HNP
      can heal spontaneously due to spontaneous resorption. Besides pressure nucleus
      pulposus, without any compression, may induce similar changes when applied
      epidurally to the nerve roots. Nevertheless, combination of chronic mechanical
      compression and application of nucleus pulposus causes a more pronounced nerve
      injury. When dual pathophysiology (pressure and inflammatory reaction),
      spontaneous resorption, and natural course of HNP are taken into account, any
      treatment modality that eliminates both the pressure and contact of the nucleus
      pulposus with the nerve root via creating extra time for healing to take place
      might prove beneficial. These requirements can be provided by spinal balloon
      nucleoplasty (SBN), which can be used in combination with other treatment
      modalities such as chymopapain injection. In this hypothetical method, epidural
      access to the subarachnoid space is established via epidural needles, thereafter
      a specially designed balloon tipped catheter is advanced. When the catheter is
      ideally placed with the help of CT or MRI, the balloon at the tip is inflated to
      relieve pressure and to prevent contact of the nerve root with HNP. The answer to
      the question, will SBN find a place in clinical practice? is obscure. But a
      homology can be established with uterine fibroid embolization, which has found
      clinical use in a period of 30 years approximately.

PMID- 18096324
TI  - RNAi-mediated gene silencing as a principle of action of venoms and poisons.
AB  - RNA interference (RNAi) is a natural phenomenon in which double-stranded RNA
      molecules (dsRNAs) promote silencing of genes with similar sequence. It is
      noteworthy that in some instances the effects of gene silencing are similar to
      those caused by venoms and natural poisons (e.g., hemorrhage and low blood
      pressure). This observation raises the possibility that venomous/poisonous
      species in fact produce dsRNAs in their venoms/poisons and leading to the
      deleterious effects in the victim by RNAi-mediated gene silencing. Two approaches
      could be used to test this hypothesis, first, the neutralization of the dsRNAs
      and comparing to a non-treated venom sample; and second, to identify the dsRNA
      present in the venom and attempt to artificially reproduce its effects in the
      laboratory. In addition, we present three innovative treatment strategies for
      accidental interactions with venomous or poisonous species. RNAi has several
      roles in biological systems: gene regulation, antiviral defense, transposon
      silencing and heterochromatin formation. The hypothesis presented here provides a
      new role: a natural attack mechanism.

PMID- 18096325
TI  - Acute morphological changes in guinea-pig ileum myenteric neurons after ischemia
      in situ with superfusion in vitro.
AB  - We evaluated changes involving the myenteric neurons of the guinea pig after
      different times of ischemia in situ followed by superfusion in vitro. Intestinal
      ischemia was produced by clamping the superior mesenteric artery and maintaining
      it for 5, 10, 20, 40, 80, or 160 min. Myenteric plexus-longitudinal muscle
      preparations from ischemic and non-ischemic portions, obtained from the same
      guinea pig, were dissected and mounted in organ baths containing Krebs
      bicarbonate solution at 37 degrees C, gassed with 95% O(2) and 5% CO(2). After 2
      h of superfusion, ischemic and non-ischemic strips were removed, immersed in a
      fixative solution, and processed for light and electron microscopy. We found that
      ultrastructural neuronal changes, which corresponded with light microscopy
      findings, developed over time. Some structural changes started after 10 min of
      ischemia, including cell swelling, chromatin clumping, vacuolization, and
      disruption of protoplasmic and mitochondrial membranes. Smooth muscle cells
      changes paralleled those observed in the myenteric neurons, but were evidenced
      until 40 min of ischemia were completed. These results show that ischemia
      produces acute time-dependent structural changes in the guinea-pig small
      intestine, and that affected cells exhibit primarily morphological changes
      characteristic of necrosis.

PMID- 18096326
TI  - Polypoid gastrointestinal stromal tumor of small bowel metastasizing to
      mesenteric lymph nodes: a case report.
AB  - Gastrointestinal stromal tumor (GIST) is the commonest gastrointestinal
      mesenchymal tumor, which rarely metastasizes to lymph nodes. Therefore, unlike
      cases of adenocarcinoma, lymphadenectomy is seldom warranted. We describe an
      unusual case of a polypoid GIST of the small bowel which metastasized to the
      regional mesenteric lymph nodes at the time of primary surgery. The patient was a
      79-year-old female who presented with partial bowel obstruction and anemia. The
      presented case has three unusual features, as the tumor was grossly pedunculated,
      microscopically pleomorphic, and featured mesenteric lymph node metastasis at the
      time of diagnosis.

PMID- 18096327
TI  - Lung granulomas from Mycobacterium tuberculosis/HIV-1 co-infected patients
      display decreased in situ TNF production.
AB  - Tuberculosis/HIV-1 co-infection is responsible for thousands of deaths each year,
      and previous studies have reported that co-infected individuals display major
      morphological alterations in tissue granulomas. The purpose of this study was to
      evaluate immunohistopathological characteristics in lung tissues from pulmonary
      TB/HIV-1-co-infected individuals. Following autopsy, tuberculosis-positive HIV-1
      negative cases displayed granulomas with normal architecture, mainly composed of
      a mononuclear infiltrate with typical epithelioid, as well as giant cells, and
      exhibiting caseous necrosis. In contrast, lesions from the TB/HIV-1-co-infected
      group showed extensive necrosis, poorly formed granulomas, and a marked presence
      of polymorphonuclear cells. More importantly, TNF staining was greatly reduced in
      the TB/HIV-1-co-infected individuals. Our data suggest that HIV-1 infection
      alters the organization of pulmonary granulomas by modulating TNF and, possibly,
      cell trafficking, leading to an impaired anti-tuberculosis response.

PMID- 18096328
TI  - Digital workflow management for quality assessment in pathology.
AB  - Information systems (IS) are well established in the multitude of departments and
      practices of pathology. Apart from being a collection of doctor's reports, IS can
      be used to organize and evaluate workflow processes. We report on such a digital
      workflow management using IS at the Department of Pathology, University Hospital
      Magdeburg, Germany, and present an evaluation of workflow data collected over a
      whole year. This allows us to measure workflow processes and to distinguish the
      effects of alterations in the workflow for quality assessment. Moreover, digital
      workflow management provides the basis for the integration of diagnostic virtual
      microscopy.

PMID- 18096329
TI  - Discrimination: from behaviour to brain.
AB  - Discrimination is a skill needed by many organisms for survival: decisions about
      food, shelter, and mate selection all require the ability to distinguish among
      stimuli. This article reviews the how and why of discrimination and how
      researchers may exploit this natural skill in the laboratory to learn more about
      what features of stimuli animals use to discriminate. The paper then discusses
      the possible neurophysiological basis of discrimination and proposes a model,
      based on one of stimulus-association put forth by Beninger and Gerdjikov (2004)
      [Beninger, R.J., Gerdjikov, T.V., 2004. The role of signaling molecules in reward
      related incentive learning. Neurotox. Res., 6, 91-104], to account for the role
      of dopamine in how an animal learns to discriminate rewarded from non-rewarded
      stimuli.

PMID- 18096330
TI  - Otoacoustic emissions does not currently have ability to detect SIDS.

PMID- 18096331
TI  - Non-invasive assessment of arterial stiffness in appropriate-for-gestational age
      newborn infants.
AB  - BACKGROUND: Quantitative information about the elastic properties of the large
      arteries can be obtained by determination of the pressure and the pulsatile
      changes of arterial diameter. OBJECTIVE: To study the stiffness of major branches
      (common carotid artery; CCA, abdominal aorta; AA and femoral artery; FA) in
      newborn infants. STUDY DESIGN: The arterial stiffness index (SI) values were
      measured with a phase locked loop ultrasound technique to estimate the arterial
      systolic and diastolic diameters and their correlation with blood pressure.
      SUBJECTS: We studied 62 appropriate-for-gestational age infants (between 30 and
      41 weeks of gestation at birth) including 33 preterm infants. RESULTS: The
      systolic and diastolic diameters of the CCA, AA and FA, as well as the SI,
      increased with the gestational age at birth. In the SI of the FA, there was
      considerable variation in the individual values for a given gestational age at
      birth. The gestational age associated increase in stiffness was statistically
      significant only in the CCA and the AA. Although the mechanical properties of the
      FA were significantly influenced by physical activities during the active waking
      and quiet sleeping states, the calculated SI values were less vulnerable to these
      activities in the central arteries. CONCLUSION: These results indicate that the
      SI of the FA (peripheral muscular artery) is modified appreciably by vasoactive
      stimuli. The mechanical properties of the deeper elastic arteries in newborn
      infants provide sufficiently reliable information about changes caused by
      development.

PMID- 18096332
TI  - The association of growth impairment with neurodevelopmental outcome at eight
      years of age in very preterm children.
AB  - BACKGROUND: The relative contributions of poor growth before and after birth in
      very preterm infants to subsequent outcomes at school-age are not certain. AIMS:
      To determine the associations between weight and head circumference, at birth and
      postnatally, with cognitive, academic and motor outcomes at age 8 years for very
      preterm children free of neurosensory impairment. STUDY DESIGN: This was a
      regional cohort study from the state of Victoria, Australia. SUBJECTS: 179 very
      preterm infants (<28 weeks' gestational age) born in 1991 and 1992 who were free
      of neurosensory impairment. OUTCOME MEASURES: At 8 years of age children had
      cognitive, academic and motor assessments. Weight and head circumference data
      were collected at birth, at the time of discharge (weight only), at 2 years of
      age and at 8 years of age, and growth restriction was calculated using Z-scores
      (standard deviation scores) relative to the expected mean for age. RESULTS: Very
      preterm children were significantly lighter and had smaller head circumferences
      than the reference group at all ages. Weight at any age was mostly unrelated to
      any outcomes. While head circumference at birth was not related to school-aged
      outcomes, smaller head circumferences at ages 2 and 8 years were associated with
      poorer performance in most outcome measures. Catch-up growth in weight in early
      childhood was not associated with 8-year outcomes. CONCLUSIONS: Intrauterine
      growth restriction was not substantially associated with neurodevelopmental
      status at age 8. Weight after birth had little influence, but head circumference
      became more important in early childhood.

PMID- 18096333
TI  - Kisspeptin-10 stimulates the secretion of growth hormone and prolactin directly
      from cultured bovine anterior pituitary cells.
AB  - Kisspeptins are peptide hormones encoded by the KiSS-1 gene, and act as the
      principal positive regulator of the reproductive axis by directly stimulating
      gonadotropin-releasing hormone (GnRH) neuron activity. We recently observed that
      kisspeptin-10 (the minimal kisspeptin sequence necessary for receptor activation)
      also has a direct stimulating effect on luteinizing hormone (LH) secretion in
      bovine anterior pituitary (AP) cells. In the present study, we evaluated the
      direct effect of kisspeptin-10 on the secretion of other pituitary hormones,
      growth hormone (GH) and prolactin (PRL), from bovine AP cells. The AP cells,
      which were prepared from 1- or 8-month-old male calves, were incubated for 2h
      with the peptides. Kisspeptin-10 at 100 nM (P<0.05), 1000 nM (P<0.01) and 10,000
      nM (P<0.01), but not at 10 nM, significantly stimulated GH secretion from the AP
      cells of 1-month-old calves, while in 8-month-old calves it was significantly
      (P<0.05) stimulated at 1000 nM (P<0.01) and 10,000 nM (P<0.01), but not at 10nM
      and 100 nM. The response of GH to 100 nM (P<0.01), 1000 nM (P<0.05) and 10,000 nM
      (P<0.01) kisspeptin-10 in the AP cells of 1-month-old calves was significantly
      greater than in those of 8-month-old calves. All tested doses of kisspeptin-10
      had no effect on PRL secretion from AP cells of 1-month-old calves. However, 1000
      nM (P<0.05) and 10,000 nM (P<0.01), but not lower concentrations, of kisspeptin
      10 significantly stimulated PRL secretion from the AP cells of 8-month-old
      calves. The present study is, as far as we know, the first to examine the direct
      actions of kisspeptin on the secretion of GH and PRL from the bovine pituitary
      gland. Further studies are necessary to evaluate the importance of multiple
      actions of kisspeptin on the pituitary of various animals in vivo.

PMID- 18096334
TI  - Sex determination in goat by amplification of the HMG box using duplex PCR.
AB  - The objective of this study was to obtain a fast, accurate and reliable method of
      determining the sex of goat embryos prior to implantation through amplification
      of the high-motility-group (HMG) box of the sex-determining region of the Y
      chromosome (SRY) gene of the goats. Goat specific primers were designed for
      duplex polymerase chain reaction (PCR). As an internal control gene, the goat
      beta-action gene sequence was simultaneously amplified together with the HMG box
      of goat SRY gene. Males showed both 1 SRY band and 1 beta-action band, but only 1
      beta-action band was present in the agarose gel electrophoresis of females. The
      result indicated that the goat HMG-box sequence motif of SRY was male specific.
      Afterward, the optimized PCR procedure was applied in 30 embryo biopsies and the
      biopsied embryos were transferred into 30 recipient female goats. The sex of the
      13 kids proved anatomically corresponded to the sex determined by PCR (100%
      accuracy). Thus, this study showed that this duplex PCR method can be applied to
      sex the goat pre-implantation embryos and to manipulate the sex ratio of
      offspring in goat breeding programs.

PMID- 18096335
TI  - Factor analysis of Greene's Climacteric Scale for Indian women.
AB  - OBJECTIVE: Do a factor analysis of the Greene Climacteric Scale for a population
      of Indian perimenopausal women and establish normative values. METHODS: Five
      hundred and eighteen women, in the age range 45-55 years, were selected and asked
      to fill out the Greene Climacteric Scale. RESULTS: The mean age of the women was
      48.03+/-3.40 years. A factor analysis of the data using an oblique rotation
      yielded three distinct factors with loadings more than 0.4. The breakup of the
      psychological factor into an anxiety and a depression factor which has been
      hypothesized earlier could only be verified using varimax rotation. The last
      item, "Loss of sexual interest" is shown to be part of the vasomotor factor. The
      means of the scores on the three factors are: psychological: 8.28+/-5.87,
      somatic: 4.64+/-3.73 and vasomotor: 2.39+/-2.10. These are much lower than the
      values given by Greene, but are in consonance with values published in two
      earlier studies for different populations.

PMID- 18096336
TI  - Core-modified chitosan-based polymeric micelles for controlled release of
      doxorubicin.
AB  - Amphiphilic stearic acid-grafted chitosan oligosaccharide (CSO-SA) micelles have
      been shown a good drug delivery system by incorporating hydrophobic drugs into
      the core of the micelles. One of the problems associated with the use of CSO-SA
      micelles is disassociation or the initial burst drug release during the dilution
      of drug delivery system by body fluid. Herein, the core of CSO-SA micelles was
      modified by the physical solubilization of stearic acid (SA) to reduce the burst
      drug release and enhance the physical stability of CSO-SA micelles. The CSO-SA
      micelles had 27.4+/-2.4 nm number average diameter, and indicated pH-sensitive
      properties. The micelle size and drug release rate from micelles increased with
      the decrease of pH value. After the incorporation of SA into CSO-SA micelles, the
      micelle size was increased, and the zeta potential was decreased. The extents of
      the increase in micelle size and the decrease of zeta potential related with the
      incorporated amount of SA. The in vitro drug release tests displayed the
      incorporation of SA into CSO-SA micelles could reduce the drug release from the
      micelles due to the enhanced hydrophobic interaction among SA, hydrophobic drug
      and hydrophobic segments of CSO-SA.

PMID- 18096337
TI  - Antibacterial activity of plants used in traditional medicines of Ghana with
      particular reference to MRSA.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: : In an ethno botanical survey carried out in the
      Akwapim-North district of the Republic of Ghana, 25 plant species, used in
      traditional medicine to treat skin disease and/or to treat antimicrobial (viral,
      bacterial or protozoan) infections were identified. AIM OF STUDY: : To
      investigate the antimicrobial activity of traditional Ghanaian medicines with
      special interest in anti-methicillin-resistant Staphylococcus aureus (MRSA)
      activity. MATERIALS AND METHODS: : Chloroform, ethanol and aqueous extracts
      (including use of a Stomacher) of these plants were prepared and agar-well
      diffusion tests, MIC's and MBC's were used to investigate antimicrobial activity.
      RESULTS: Extracts of 13 plant species inhibited the growth of one or more of the
      following bacteria: MRSA, methicillin-sensitive Staphylococcus aureus (MSSA),
      Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and Proteus
      vulgaris. Extracts from 11 of these 13 plant species also inhibited the growth of
      three or more of 14 additional clinical isolates of MRSA. Aqueous extracts of
      Alchornea cordifolia were active against all 21 bacterial strains tested and
      showed the highest levels of antibacterial activity overall with MIC's against
      MRSA in the range of 1.6-3.1 mgml(-1) and MBC's in the range of 6.3-12.5 mgml(
      1). CONCLUSIONS: : The presence of antibacterial activity in extracts of
      Elaeophorbia drupifera, Rauwolfia vomitoria and the leaves of Solanum
      verbascifolium, plants traditionally used to treat skin infections, are reported
      for the first time. Extracts from Alchornea cordifolia, also used to treat
      wounds, had the widest spectrum of antibacterial activity.

PMID- 18096338
TI  - Controlled electrostatic methodology for imaging indentations in documents.
AB  - The electrostatic process for imaging indentations on documents using the ESDA
      device is investigated under controlled experimental settings. An in-house
      modified commercial xerographic developer housing is used to control the
      uniformity and volume of toner deposition, allowing for reproducible image
      development. Along with this novel development tool, an electrostatic voltmeter
      and fixed environmental conditions facilitate an optimization process. Sample
      documents are preconditioned in a humidity cabinet with microprocessor control,
      and the significant benefit of humidification above 70% RH on image quality is
      verified. Improving on the subjective methods of previous studies, image quality
      analysis is carried out in an objective and reproducible manner using the PIAS
      II. For the seven commercial paper types tested, the optimum ESDA operating point
      is found to be at an electric potential near -400V at the Mylar surface; however,
      for most paper types, the optimum operating regime is found to be quite broad,
      spanning relatively small electric potentials between -200 and -550V. At -400V,
      the film right above an indented area generally carries a voltage which is 30-50V
      less negative than the non-indented background. In contrast with Seward's
      findings [G.H. Seward, Model for electrostatic imaging of forensic evidence via
      discharge through Mylar-paper path, J. Appl. Phys. 83 (3) (1998) 1450-1456; G.H.
      Seward, Practical implications of the charge transport model for electrostatic
      detection apparatus (ESDA), J. Forensic Sci. 44 (4) (1999) 832-836], a period of
      charge decay before image development is not required when operating in this
      optimal regime. A brief investigation of the role played by paper-to-paper
      friction during the indentation process is conducted using our optimized
      development method.

PMID- 18096339
TI  - Efficient height measurement method of surveillance camera image.
AB  - As surveillance cameras are increasingly installed, their films are often
      submitted as evidence of crime, but very scant detailed information such as
      features and clothes is obtained due to the limited camera performance. Height,
      however, is relatively not significantly influenced by the camera performance.
      This paper studied the height measurement method using images from a CCTV. The
      information on the height was obtained via photogrammetry, including the
      reference points in the photographed area and the calculation of the relationship
      between a 3D space and a 2D image through linear and nonlinear calibration. Using
      this correlation, this paper suggested the height measurement method, which
      projects a 3D virtual ruler onto the image. This method has been proven to offer
      more stable values within the range of data convergence than those of other
      existing methods.

PMID- 18096340
TI  - [Two cases of Lactobacillus rhamnosus infection and pancreatitis].
AB  - Lactobacilli rhamnosus infections are rare and occur in patients with severe
      conditions causing immunosuppression and/or in those who have received intense
      antibiotic treatment such as with teicoplanin and vancomycin. We report two cases
      which occurred within a period of 48 hours, during regression of pancreatitis in
      two women aged 35 and 70 years old, hospitalized in the same department. Several
      criteria pointed towards two independent infections but the rarity and chronology
      of the appearance of these infections raised the question of possible cross
      contamination. Lactobacillus rhamnosus was isolated in intra-abdominal samples
      from both patients, and in blood cultures from one of them. Specimens were
      monomicrobial. The description of these observations shows the limits of
      molecular biology for identifying the Lactobacillus rhamnosus strain: it was not
      possible to determine whether a single clone or two different clones were
      involved.

PMID- 18096341
TI  - Hepatitis A: a rare cause of acalculous cholecystitis in children.

PMID- 18096342
TI  - Indications for body MRI Part II: retroperitoneum, intestines and pelvis.
AB  - In this article an overview is given of the present knowledge of whole body MRI,
      MRI of the retroperitoneum, intestines and pelvis. Recommendations are based on
      current literature and clinical applications in daily routine focusing on
      efficacy rather than cost considerations. The contribution and complementary role
      of MRI relative to those of its competing modalities was the most important
      endpoint assessed. Perfusion and functional information, as well as specific
      contrast agents in the area of the pelvis are still considered research
      indications.

PMID- 18096343
TI  - Clinical evaluation of sodium hyaluronate in the treatment of patients with
      sopraspinatus tendinosis under echographic guide: experimental study of
      periarticular injections.
AB  - PURPOSE: The purpose of this study was to examine the effect of periarticular
      injection of hyaluronate into shoulders with supraspinatus tendinosis under
      echographic guide. METHODS AND MATERIALS: The subjects were 56 patients with
      clinical, echographic and magnetic resonance diagnosis of supraspinatus
      tendinosis. They were divided in two groups by random sampling; 28 patients were
      assigned in SH group (sodium hyaluronate) and 28 patients in SC group (sodium
      chloride). The test drug was 20mg sodium hyaluronate (2ml, Hyalgan, Fidia SpA,
      Abano T., P.M. 500-700.000, 20mg/2ml). RESULTS: Preliminary results showed that
      sodium hyaluronate presented the highest efficacy in the improvement of clinical
      symptoms and recovery of functional status in patients with supraspinatus
      tendinosis in fact the mean V.A.S. score (Visual Analogue Scale) at 1 month after
      the end of the infiltrative cycle was 8.0 in the SC group vs. 2.8 in SH group and
      these numerical data were substantially unchanged also after 3 and 4 months.
      CONCLUSION: Hyaluronate injection under echographic guide should be use not only
      as a lubricant but also to prevent articular cartilage degeneration and cover and
      protect the articular cartilage; indeed sodium hyaluronate can decrease
      inflammatory joint process.

PMID- 18096344
TI  - Whole-body MRI of multiple myeloma: comparison of different MRI sequences in
      assessment of different growth patterns.
AB  - PURPOSE: To determine sensitivity, specificity and inter-observer variability of
      different whole-body MRI (WB-MRI) sequences in patients with multiple myeloma
      (MM). METHODS AND MATERIALS: WB-MRI using a 1.5T MRI scanner was performed in 23
      consecutive patients (13 males, 10 females; mean age 63+/-12 years) with
      histologically proven MM. All patients were clinically classified according to
      infiltration (low-grade, n=7; intermediate-grade, n=7; high-grade, n=9) and to
      the staging system of Durie and Salmon PLUS (stage I, n=12; stage II, n=4; stage
      III, n=7). The control group consisted of 36 individuals without malignancy (25
      males, 11 females; mean age 57+/-13 years). Two observers independently evaluated
      the following WB-MRI sequences: T1w-TSE (T1), T2w-TIRM (T2), and the combination
      of both sequences, including a contrast-enhanced T1w-TSE with fat-saturation
      (T1+/-CE/T2). They had to determine growth patterns (focal and/or diffuse) and
      the MRI sequence that provided the highest confidence level in depicting the MM
      lesions. Results were calculated on a per-patient basis. RESULTS: Visual
      detection of MM was as follows: T1, 65% (sensitivity)/85% (specificity); T2,
      76%/81%; T1+/-CE/T2, 67%/88%. Inter-observer variability was as follows: T1, 0.3;
      T2, 0.55; T1+/-CE/T2, 0.55. Sensitivity improved depending on infiltration grade
      (T1: 1=60%; 2=36%; 3=83%; T2: 1=70%; 2=71%; 3=89%; T1+/-CE/T2: 1=50%; 2=50%;
      3=89%) and clinical stage (T1: 1=58%; 2=63%; 3=79%; T2: 1=58%; 2=88%; 3=100%;
      T1+/-CE/T2: 1=50%; 2=63%; 3=100%). T2w-TIRM sequences achieved the best
      reliability in depicting the MM lesions (65% in the mean of both readers).
      CONCLUSIONS: T2w-TIRM sequences achieved the highest level of sensitivity and
      best reliability, and thus might be valuable for initial assessment of MM. For an
      exact staging and grading the examination protocol should encompass unenhanced
      and enhanced T1w-MRI sequences, in addition to T2w-TIRM.

PMID- 18096345
TI  - Deinococcus misasensis and Deinococcus roseus, novel members of the genus
      Deinococcus, isolated from a radioactive site in Japan.
AB  - Two gamma- and UV-radiation resistant, Gram-positive, red- or pink-pigmented, rod
      shaped, strictly aerobic, oxidase- and catalase-positive bacterial strains, TDMA
      25T and TDMA-uv51T, were isolated from fresh water collected at Misasa, a
      radioactive site in Japan. Phylogenetic analysis based on 16S rRNA gene sequences
      placed both in a distinct lineage in the family Deinococcaceae, and the highest
      degrees of sequence similarity determined belonged to Deinococcus maricopensis LB
      34T (88.8-89.3%), Deinococcus pimensis KR-235T (86.4-86.7%) and Deinococcus
      yavapaiensis KR-236T (86.1%). The DNA G+C content of the strains was 53-58 mol%.
      The major respiratory quinone was MK-8. The predominant fatty acids were C15:0
      iso, C16:0 iso, C13:0 iso, C17:0 iso, C16:0, C13:0 anteiso, C15:0 and C12:0 iso.
      The strains degraded gelatin, casein, starch and Tween 80. Unique physiological
      characteristics, differences in their fatty acid profiles, and genotypic and
      phylogenetic features, differentiated strains TDMA-25T and TDMA-uv51T from
      closely related Deinococcus species. Hence, the two strains are described as
      novel species of the genus Deinococcus. The names Deinococcus misasensis sp. nov.
      (type strain TDMA-25T=JCM 14369=NBRC 102116=CCUG 53610) and Deinococcus roseus
      sp. nov. (type strain TDMA-uv51T=JCM 14370=NBRC 102117=CCUG 53611) are proposed.

PMID- 18096346
TI  - Two-dimensional ultrashort echo time imaging using a spiral trajectory.
AB  - Tissues with very short transverse relaxation time (T2) cannot be detected using
      conventional magnetic resonance (MR) sequences due to the rapid decay of excited
      MR signals. In this work, a multiecho sequence employing half-pulse excitation
      and spiral sampling was developed for ultrashort echo time (UTE) imaging of
      tissues with short T2. Spiral readout gradients were measured and precompensated
      to reduce gradient distortions due to eddy currents and gradient anisotropy. The
      effects of spatial blurring due to fast signal decay were investigated
      experimentally through spiral UTE (SUTE) imaging of rubber bands with different
      spiral sampling duration. The unwanted long T2 signals were suppressed through
      the use of an inversion pulse and nulling, and/or subtraction of a later echo
      image from the initial one. This technique has been applied to imaging of the
      short T2 components in brain white matter, knee cartilage, bone and carotid
      vessel wall of normal volunteers at 1.5 T. Preliminary results show high spatial
      resolution and excellent image contrast for a variety of short T2 tissues in the
      human body under a relatively short scan time. A quantitative comparison was also
      made between radial UTE and SUTE in terms of signal-to-noise ratio efficiency.

PMID- 18096348
TI  - Simultaneous determination of aceclofenac and its three metabolites in plasma
      using liquid chromatography-tandem mass spectrometry.
AB  - A new LC/MS/MS-based method allows simultaneous determination of aceclofenac and
      its three metabolites (4'-OH-aceclofenac, diclofenac, and 4'-OH-diclofenac) in
      plasma. After acetonitrile-induced precipitation of proteins from the plasma
      samples, aceclofenac, 4'-OH-aceclofenac, diclofenac, 4'-OH-diclofenac, and
      flufenamic acid (an internal standard) were chromatographed on a reverse-phase
      C(18) analytical column. The isocratic mobile phase of acetonitrile/0.1% formic
      acid((aq)) [80:20 (v/v)] was eluted at 0.2 mL/min. Quantification was performed
      on a triple-quadrupole mass spectrometer employing electrospray ionization, and
      the ion transitions were monitored in multiple reaction-monitoring mode. The
      monitored transitions for aceclofenac, diclofenac, 4'-OH-diclofenac, 4'-OH
      aceclofenac and flufenamic acid were m/z 352.9-->74.9, 296.1-->251.7, 311.8-
      >267.7, 368.9-->74.9, and 279.9-->235.9, respectively. The coefficient of
      variation of the assay precision was less than 6.5%, and the accuracy ranged from
      93% to 103%. The limits of detection were 2 ng/mL for aceclofenac and 0.2 ng/mL
      for both diclofenac and 4'-OH-diclofenac. This method was used successfully to
      measure the concentrations of aceclofenac and its three metabolites in plasma
      from healthy subjects after administration of a single 100-mg oral dose of
      aceclofenac. This analytic method is a very simple, sensitive, and accurate way
      to determine the pharmacokinetics of aceclofenac and its metabolites.

PMID- 18096347
TI  - Quantitative aspects of the analysis of the monoclonal antibody trastuzumab using
      high-performance liquid chromatography coupled with electrospray mass
      spectrometry.
AB  - The analytical possibilities of quantification of the intact monoclonal antibody
      trastuzumab by high-performance liquid chromatography coupled with electrospray
      mass spectrometry (HPLC-ESI-MS) were investigated. To clarify the results
      obtained by LC-MS, complementary experiments were performed using direct UV
      spectrophotometry and high-performance liquid chromatography coupled with
      ultraviolet detection (HPLC-UV). A polystyrene-divinylbenzene (POROS) column was
      applied with gradient elution using formic acid 0.08% (v/v) in water and formic
      acid 0.08% (v/v) in acetonitrile as mobile phase for chromatographic analysis.
      Quantification on LC-MS was performed by using the peak area of the total ion
      current (TIC) chromatograms of one charge state. Non-linearity and sensitivity
      loss were the major limitations observed with the LC-MS method, of which the non
      linearity is most likely caused by detector saturation. The sensitivity loss
      during analysis could be reduced by lowering the MS source temperature. This
      parameter is critical in creating a robust LC-MS system for the quantitative
      analysis of trastuzumab.

PMID- 18096349
TI  - Determination of sitagliptin in human urine and hemodialysate using turbulent
      flow online extraction and tandem mass spectrometry.
AB  - High turbulence liquid chromatography (HTLC, or turbulent flow online extraction)
      and tandem mass spectrometry (MS/MS) methods for the determination of sitagliptin
      in human urine and hemodialysate were developed and validated to support clinical
      studies. A narrow bore large particle size reversed-phase column (Cyclone, 50 mm
      x 1.0 mm, 60 microm) and a BDS Hypersil C18 column (30 mm x 2.1 mm, 3 microm)
      were used as extraction and analytical columns, respectively. For the urine
      assay, the LLOQ was 0.1 microg/ml, the linear calibration range was 0.1 to 50
      microg/ml, the interday precision (R.S.D.%, n=5) was 2.3-6.5%, and the accuracy
      was 96.9-106% of the nominal value. For the urine quality control samples (QCs),
      the intraday precision (R.S.D.%, n=5) and accuracy were 1.8-2.6% and 96.2-106% of
      the nominal value, respectively. The interday precision (R.S.D.%) for 56 sets of
      urine QCs over a 6-month period varied from 3.8% to 5.5% and the accuracy from
      102% to 105% of the nominal value. For the hemodialysate assay, the LLOQ was 0.01
      ng/ml, the linear dynamic range was 0.01-5.0 ng/ml, the interday precision was
      1.6-4.1%, and the accuracy was 89.8-104% of the nominal value. For hemodialysate
      QCs, the intraday precision and accuracy varied from 2.3% to 8.9% and from 99.8%
      to 111% of the nominal value, respectively. These results demonstrated that both
      methods are selective, accurate, precise, reproducible, and suitable for
      quantifying sitagliptin in hemodialysate and human urine samples.

PMID- 18096350
TI  - Impurities of tazarotene: isolation and structural characterisation.
AB  - Two impurities showing structures 5 and 6 were isolated and characterised by
      means of NMR analysis, during the optimisation of a synthetic procedure to
      tazarotene. Impurity 5, i.e. ethyl 6-((4,4-dimethyl-4H-thiochromen-6
      yl)ethynyl)nicotinate, was a by-product of the reduction of the intermediate
      sulfoxide 7 with PCl(3). Impurity 6, i.e. 1,4-bis(4,4-dimethylthiochroman-6
      yl)buta-1,3-diyne, was due to a side reaction of the Sonogashira coupling.

PMID- 18096351
TI  - Detection of parvovirus B19 in synovial fluids of patients with osteoarthritis.
AB  - We aimed to determine the possible role of parvovirus B19 (PVB19) in the etiology
      of osteoarthritis. PVB19 DNA, anti-VP1 IgM and IgG, and interleukin IL-6 levels
      were also assayed in synovial fluids of 42 patients with osteoarthritis and 10
      controls. PVB19 DNA was detected in 28 of 42 (66.66%) in patients and in 3 of 10
      (30%) in controls. IgG and IgM response were detected in 21 of 42 (50.00%) and in
      2 of 42 (4.76%) patients, respectively. IL-6 were positive in 15 of 42 (36%)
      patients and in 3 of 10 (30%) controls. All IgG (+) samples had PVB19 DNA (100%,
      P < 0.001). Eleven of 15 IL-6 (+) samples had PVB19 DNA (+) (73.33%, P < 0.05).
      Moreover, all IL-6 (+) samples (n = 5) in stage IV had PVB19 DNA (+) (100%, P <
      0.001). We have detected a significant association between the stages of
      osteoarthritis and PVB19 DNA (P < 0.05). These findings support the presence of
      PVB19 acting as a transactivator of IL-6 expression as reported earlier. Our
      results also suggest that the higher stages of osteoarthritis might be related to
      the increased inflammation and cell damage on joint cartilage due to PVB19.

PMID- 18096352
TI  - Diminished vancomycin and daptomycin susceptibility during prolonged bacteremia
      with methicillin-resistant Staphylococcus aureus.
AB  - An elderly patient with methicillin-resistant Staphylococcus aureus (MRSA)
      bacteremia was treated sequentially with vancomycin plus rifampin then daptomycin
      plus gentamicin. The MRSA strain developed diminished susceptibility to
      vancomycin (MIC increase and tolerance), daptomycin, and gentamicin, and
      resistance to rifampin during therapy.

PMID- 18096353
TI  - Adapting to major chronic illness: a proposal for a comprehensive task-model
      approach.
AB  - OBJECTIVE: To develop a comprehensive task-based model that describes the
      psychosocial adaptation process to major chronic illness. METHOD: In order to
      achieve this objective, we reviewed the four task-based models: those of Moos and
      Tsu [Moos RH, Tsu DV. Coping with physical illness. New York: Plenum Medical
      Company; 1977], Cohen and Lazarus [Cohen F, Lazarus RS. Coping with the stress of
      illness. In: Stone CG, Cohen F, Adler NE, editors. Health psychology: a handbook.
      San Francisco, CA: Jossey-Bass; 1979. p. 217-54], Corr [Corr C. A task-based
      approach to coping with dying. Omega 1992;24:81-94] and Samson [Samson A.
      L'apport de la carriere au modele theorique des taches d'adaptation a la maladie
      chronique: une application au cas des personnes qui vivent avec le VIH. Can J
      Couns 2006;40:4-16]. RESULTS: We propose a comprehensive task-based model that
      gives a comprehensive description of the process of psychosocial adaptation to
      chronic illness. CONCLUSION: With the gradual rise in life expectancy and quality
      of living for individuals diagnosed with major chronic illnesses, it is becoming
      increasingly relevant to understand how these individuals adapt to their
      conditions over the long term. The comprehensive model allows medical
      professionals to look at the challenges of this process from both objective and
      subjective points of view. PRACTICE IMPLICATIONS: To enhance current practice by
      helping professionals to conceptualize their patients' process of adaptation to
      chronic illness in a holistic manner.

PMID- 18096354
TI  - Cancer care communication: the power to harm and the power to heal?
AB  - OBJECTIVE: This study was designed to examine the belief held by many cancer
      patients that communication with their care providers has a meaningful part to
      play in shaping their disease outcomes. METHODS: From a large qualitative
      interview data set in which cancer patients described their perceptions of
      helpful and unhelpful heath care communication; we extracted the accounts of 69
      patients and 13 focus group participants who specifically articulated a perceived
      relationship between communication and cancer outcomes. Through secondary
      analysis of that subset, we generated an interpretive description of patterns and
      themes within their accounts of a relationship between communication and cancer
      survivorship. RESULTS: Our findings document patient perceptions of the
      mechanisms involved in indirect and, some instances, direct relationships between
      communication encounters and cancer outcomes. CONCLUSION: Some cancer patients
      believe that, by virtue of its influence upon comfort, inclusion, clarity and
      hope, communication can influence cancer outcomes. PRACTICE IMPLICATIONS: While
      competing discourses exist within the patient population with regard to such
      associations, the perception that communication may influence clinical outcomes
      seems sufficiently pervasive and persistent that it warrants serious attention
      within care systems and by the psychosocial cancer research community.

PMID- 18096355
TI  - Exploration of associations between phospholipase A2 gene family polymorphisms
      and AIDS progression using the SNPlex method.
AB  - Members of the secreted phospholipase A2 (PLA2) protein family can inhibit HIV-1
      virus replication in vitro. To evaluate the impact of PLA2 gene polymorphisms on
      AIDS disease development, we studied 12 family members using SNPlextrade mark
      technology that permitted simultaneous typing of 70 tagging Single Nucleotide
      Polymorphisms (tagSNPs). The study utilized HIV-1 seropositive donors with slow
      progressor (n=168) or rapid progressor (n=54) status, plus 355 control subjects.
      All donors were Caucasian (total 577 individuals). Genetic associations yielded
      mainly 0.01<p<0.05, but lower p-values were obtained for four tagSNPs and seven
      haplotype alleles. These stronger associations corresponded to both secreted
      (PLA2G2A, PLA2G2D and PLA2G3) and cytosolic (PLA2G4A and PLA2G6) PLA2 genes,
      including three (PLA2G2A, PLA2G2D and PLA2G4A) implicated in the pathogenesis of
      other diseases. Our results suggest that the PLA2 gene family may represent genes
      of interest for a larger study targeting all the known tagSNPs in the PLA2 genes.
      The data presented in this study will have to be confirmed in other AIDS cohorts
      and will also be useful for studies undertaken on the PLA2 gene family in other
      disease cohorts.

PMID- 18096357
TI  - [Mass screening for colorectal cancer with the guaiac fecal occult blood test:
      possible population benefits, proven individual risks].

PMID- 18096356
TI  - [Celiac disease associated with Budd-Chiari syndrome].
AB  - INTRODUCTION: Budd-Chiari syndrome is a rare disease defined by obstruction of
      the hepatic portal vein. Its association with celiac disease is rare. CASE: We
      report the case of a 28-year-old woman who presented with celiac disease
      associated with Budd-Chiari syndrome for which no cause could be found. A gluten
      free diet and antivitamin K treatment led to a favorable outcome. DISCUSSION:
      This case and a review of the literature suggest that the pathogenesis of these
      two disorders is linked.

PMID- 18096358
TI  - [Dissecting intramural hematoma of the esophagus: a rare cause of chest pain].
AB  - INTRODUCTION: Dissecting intramural hematoma of the esophagus is a rare cause of
      chest pain that can be misinterpreted as a myocardial infarction. The use of
      anticoagulants in this case may lead to hemorrhagic complications. CASE: A 51
      year-old patient, with coronary artery disease, diabetes, hypertension and
      dependent on both alcohol and tobacco, was admitted for chest pain and an
      elevated troponin T plasma level. He was treated with anticoagulants. He
      developed hematemesis on the third day and was transferred to intensive care.
      Esophageal endoscopy revealed a hematoma with active bleeding, covered by
      esophageal mucosa from the middle to the lower third of the esophagus (for 13
      cm). Computed tomography allowed us to rule out an aortoesophageal fistula.
      Symptomatic treatment consisted of withdrawing the anticoagulant, mechanical
      ventilation, intravenous sedation, and blood transfusion. The patient recovered,
      after a long stay in ICU. DISCUSSION: Intramural dissecting hematoma of the
      esophagus is not always easy to diagnose. Administration of anticoagulant
      treatment after a misdiagnosis of acute coronary syndrome can have serious
      hemorrhagic consequences. Prognosis is excellent with conservative treatment.

PMID- 18096359
TI  - Paraquat toxicity in a mouse embryonic stem cell model.
AB  - The objective of this in vitro study was to use a mouse embryonic stem (mES) cell
      model to better understand pesticide injury that may adversely affect early
      pregnancy and to evaluate an antioxidant intervention. Undifferentiated D3 mES
      cells were incubated 24h with control, reference dose (RfD), no observed effect
      level (NOEL), or lowest observed effect level (LOEL) of paraquat, a commonly
      used, toxic agricultural herbicide. Pesticide effects were evaluated at 0 and 24h
      using assays for cell proliferation, total reactive oxygen species (ROS),
      viability, and alkaline phosphatase activity. Compared to 0 h, cell proliferation
      increased significantly in the 24h control treatment and was stalled in all
      paraquat dilutions tested. ROS production and percent necrotic and apoptotic
      cells were significantly increased at all paraquat concentrations examined.
      Alkaline phosphatase activity suggested that cells remained undifferentiated
      during the study period. Experiments with ascorbic acid suggested that pesticide
      effects on cell viability and ROS production were minimized by the recommended
      daily allowance (RDA) of vitamin C. Data suggest pesticide-induced injury can
      occur very early in development and at concentrations predicted without health
      consequences. Mouse ES cells may provide a useful in vitro model for rapidly
      screening developmental toxicants and protective interventions.

PMID- 18096360
TI  - Assessment of executive functions: review of instruments and identification of
      critical issues.
AB  - "Executive functions" is an umbrella term for functions such as planning, working
      memory, inhibition, mental flexibility, as well as the initiation and monitoring
      of action. The impairment of executive functions in various clinical groups is a
      topic of much debate, as are recent attempts to formulate the corresponding
      intervention and rehabilitation regimes of these dysfunctions. This article
      reviewed current theories of executive functions and their associated assessment
      instruments. In addition, it identified issues that are imperative for more
      accurate, sensitive, and specific assessment of various components of this
      construct. It is concluded that more research is needed to fractionate the
      executive system by assessing a wide range of functions and to verify their
      neuroanatomical correlates. Recently developed measurement models and technology
      may also facilitate a more ecologically and ethologically valid assessment for
      the specific needs of different individuals.

PMID- 18096361
TI  - Phylogenetic analysis of vertebrate kininogen genes.
AB  - Kininogens, the precursors of bradykinins, vary extremely in both structure and
      function among different taxa of animals, in particular between mammals and
      amphibians. This includes even the most conserved bradykinin domain in terms of
      biosynthesis mode and structure. To elucidate the evolutionary dynamics of
      kininogen genes, we have identified 19 novel amino acid sequences from EST and
      genomic databases (for mammals, birds, and fishes) and explored their
      phylogenetic relationships using combined amino acid sequence and gene structure
      as markers. Our results show that there were initially two paralogous kininogen
      genes in vertebrates. During their evolution, the original gene was saved with
      frequent multiplication in amphibians, but lost in fishes, birds, and mammals,
      while the novel gene was saved with multiple functions in fishes, birds, and
      mammals, but became a pseudogene in amphibians. We also propose that the defense
      mechanism against specific predators in amphibian skin secretions has been
      bradykinin receptor dependent. Our findings may provide a foundation for
      identification and structural, functional, and evolutionary analyses of more
      kininogen genes and other gene families.

PMID- 18096362
TI  - The role of thrombolysis in acute infrainguinal bypass occlusion: a prospective
      nonrandomized controlled study.
AB  - Current treatment of acute infrainguinal bypass occlusion consists of either
      surgical revascularization or catheter-guided intra-arterial thrombolysis with
      adjunctive correction of the underlying flow-limiting lesion. In maintaining long
      term patency, improving the number of outflow vessels could be of utmost
      importance. To compare the efficiency of both thrombolysis and primary surgical
      revascularization and to study the effect of thrombolysis on the number of patent
      outflow vessels, a prospective nonrandomized study was performed. Between
      February 2002 and August 2003, 54 patients with 56 occluded bypasses were
      included. Thirty bypasses were treated with thrombolysis, 26 primarily with
      surgery. Thrombolysis was successful in 80% of cases, with restoration of patency
      of the bypass but also with doubling of the amount of patent outflow vessels;
      surgery was successful in 85.71% of cases. However, in only 60% of the
      successfully lysed bypasses no adjunctive major surgery was needed. Amputation
      free survival was 87.5% 1 year after surgery and 82.6% 1 year after thrombolysis.
      One year after thrombolysis without adjunctive major surgery, the amputation-free
      survival was only 39.7%. Therefore, a strategy could be to start with
      thrombolysis to improve outflow followed by a new bypass, whatever the underlying
      causative lesions are.

PMID- 18096363
TI  - Persistent cognitive alterations in rats after early postnatal exposure to low
      doses of the organophosphate pesticide, diazinon.
AB  - BACKGROUND: Developmental neurotoxicity of organophosphorous insecticides (OPs)
      involves multiple mechanisms in addition to cholinesterase inhibition. We have
      found persisting effects of developmental chlorpyrifos (CPF) and diazinon (DZN)
      on cholinergic and serotonergic neurotransmitter systems and gene expression as
      well as behavioral function. Both molecular/neurochemical and behavioral effects
      of developmental OP exposure have been seen at doses below those which cause
      appreciable cholinesterase inhibition. OBJECTIVES: We sought to determine if
      developmental DZN exposure at doses which do not produce significant
      acetylcholinesterase inhibition cause persisting cognitive deficits. METHODS:
      Rats were exposed to DZN on postnatal days 1-4 at doses (0.5 and 2 mg/kg/d) that
      span the threshold for cholinesterase inhibition. They were later examined with a
      cognitive battery tests similar to that used with CPF. RESULTS: In the T-maze DZN
      caused significant hyperactivity in the initial trials of the session, but not
      later. In a longer assessment of locomotor activity no DZN-induced changes were
      seen over a 1-hour session. Prepulse inhibition was reduced by DZN exposure
      selectively in males vs. females; DZN eliminated the sex difference present in
      controls. In the radial maze, the lower but not higher DZN dose significantly
      impaired spatial learning. This type of nonmonotonic dose-effect function has
      previously been seen with CPF as well. The lower dose DZN group also showed
      significantly greater sensitivity to the memory-impairing effects of scopolamine
      a muscarinic acetylcholine antagonist. CONCLUSIONS: Neonatal DZN exposure below
      the threshold for appreciable cholinesterase inhibition caused persisting
      neurocognitive deficits in adulthood. The addition of some inhibition of AChE
      with a higher dose reversed the cognitive impairment. This non-monotonic dose
      effect function has also been seen with neurochemical effects. Some of the DZN
      effects on cognition resemble those seen earlier for CPF, some differ. Our data
      suggest that DZN and CPF affect transmitter systems supporting memory function,
      differently, implying participation of mechanisms other than their common
      inhibition of cholinesterase.

PMID- 18096364
TI  - Effects of gestational exposure to methylmercury and dietary selenium on
      reinforcement efficacy in adulthood.
AB  - It has recently been demonstrated that developmental exposure to methylmercury
      (MeHg) is associated with perseveration on operant tasks. An understanding of the
      behavioral mechanisms underlying this phenomenon may improve human testing of
      MeHg exposures and could provide insight into clinical syndromes that include
      perseveration as a component. One possible mechanism is that MeHg-induced
      enhancement of reinforcer efficacy produces a "reinforcement trap" that inhibits
      change in novel situations. Rats were exposed gestationally to 0, 0.5 or 5 ppm
      mercury (Hg) as MeHg via maternal drinking water. They also received a diet
      during gestation and throughout life that was marginal (0.06 ppm) or rich (0.6
      ppm) in selenium (Se), a nutrient believed to protect against MeHg's toxicity.
      Reinforcer efficacy was evaluated using a progressive ratio schedule of
      reinforcement during adulthood. Maximum ratio obtained (MRO) was determined using
      20 or 60 mg sucrose pellets and with ratio requirements that increased at 5% or
      20% per reinforcer. MRO was related to the rate at which the ratio increased,
      reinforcer magnitude, sex, and exposure regimen; MRO was increased for the 0.6
      ppm Se, 5 ppm Hg group. This extends an earlier observation that developmental
      MeHg exposure enhances reinforcer efficacy, an effect that could be related to
      reports of perseveration.

PMID- 18096365
TI  - 3D CT-video fusion for image-guided bronchoscopy.
AB  - Bronchoscopic biopsy of the central-chest lymph nodes is an important step for
      lung-cancer staging. Before bronchoscopy, the physician first visually assesses a
      patient's three-dimensional (3D) computed tomography (CT) chest scan to identify
      suspect lymph-node sites. Next, during bronchoscopy, the physician guides the
      bronchoscope to each desired lymph-node site. Unfortunately, the physician has no
      link between the 3D CT image data and the live video stream provided during
      bronchoscopy. Thus, the physician must essentially perform biopsy blindly, and
      the skill levels between different physicians differ greatly. We describe an
      approach that enables synergistic fusion between the 3D CT data and the
      bronchoscopic video. Both the integrated planning and guidance system and the
      internal CT-video registration and fusion methods are described. Phantom, animal,
      and human studies illustrate the efficacy of the methods.

PMID- 18096366
TI  - Semaphorin3A regulates axon growth independently of growth cone repulsion via
      modulation of TrkA signaling.
AB  - Regulation of axon growth is a critical event in neuronal development. Nerve
      growth factor (NGF) is a strong inducer of axon growth and survival in the dorsal
      root ganglia (DRG). Paradoxically, high concentrations of NGF are present in the
      target region where axon growth must slow down for axons to accurately identify
      their correct targets. Semaphorin3A (Sema3A), a powerful axonal repellent
      molecule for DRG neurons, is also situated in their target regions. NGF is a
      modulator of Sema3A-induced repulsion and death. We show that Sema3A is a
      regulator of NGF-induced neurite outgrowth via the TrkA receptor, independent of
      its growth cone repulsion activity. First, neurite outgrowth of DRG neurons is
      more sensitive to Sema3A than repulsion. Second, at concentrations sufficient to
      significantly inhibit Sema3A-induced repulsion, NGF has no effect on Sema3A
      induced axon growth inhibition. Third, Sema3A-induced outgrowth inhibition, but
      not repulsion activity, is dependent on NGF stimulation. Fourth, Sema3A
      attenuates TrkA-mediated growth signaling, but not survival signaling, and over
      expression of constitutively active TrkA blocks Sema3A-induced axon growth
      inhibition, suggesting that Sema3A activity is mediated via regulation of
      NGF/TrkA-induced growth. Finally, quantitative analysis of axon growth in vivo
      supports the possibility that Sema3A affects axon growth, in addition to its well
      documented role in axon guidance. We suggest a model whereby NGF at high
      concentrations in the target region is important for survival, attraction and
      inhibition of Sema3A-induced repulsion, while Sema3A inhibits its growth
      promoting activity. The combined and cross-modulatory effects of these two
      signaling molecules ensure the accuracy of the final stages in axon targeting.

PMID- 18096368
TI  - Effects of preoperative carbohydrate loading on glucose metabolism and gastric
      contents in patients undergoing moderate surgery: a randomized, controlled trial.
AB  - OBJECTIVE: Despite contrary evidence, the practice of overnight fasting before
      elective surgery maintains its place in tradition. However, prolonged starvation,
      by its catabolic action, may increase the detrimental effects of surgery. In this
      study, we evaluated the effects of preoperative carbohydrate loading on the
      gastric contents of patients and perioperative metabolism. METHODS: Seventy
      patients scheduled for cholecystectomy or thyroidectomy randomly were assigned to
      the treatment or control group. Patients in the treatment group (n = 34) received
      800 mL of a carbohydrate-rich fluid on the evening before surgery and 400 mL of
      the same fluid 2 h preoperatively. Conversely, control patients (n = 36)
      underwent overnight fasting. Plasma glucose and serum insulin levels were
      obtained across the perioperative period and during anesthesia induction. The
      volume and pH of preoperative residual gastric contents also were measured.
      RESULTS: Preoperative plasma glucose levels were found to remain significantly
      higher in patients who had received the carbohydrate-rich fluid. Serum insulin
      levels that were elevated initially in the study group returned to control levels
      by the time of anesthesia induction. There was no statistical difference between
      the two groups with respect to gastric residue contents or gastric fluid pH.
      CONCLUSION: The preoperative intake of carbohydrate-rich fluids does not appear
      to alter the amount or pH of gastric contents, suggesting that this is a safe
      procedure, in terms of aspiration risk. Furthermore, the intake of such fluid
      might prevent energy malnutrition.

PMID- 18096367
TI  - hSef potentiates EGF-mediated MAPK signaling through affecting EGFR trafficking
      and degradation.
AB  - Sef (similar expression to fgf genes) was identified as an effective antagonist
      of fibroblast growth factor (FGF) in vertebrates. Previous reports have
      demonstrated that Sef interacts with FGF receptors (FGFRs) and inhibits FGF
      signaling, however, its role in regulating epidermal growth factor receptor
      (EGFR) signaling remains unclear. In this report, we found that hSef localizes to
      the plasma membrane (PM) and is subjected to rapid internalization and well
      localizes in early/recycling endosomes while poorly in late endosomes/lysosomes.
      We observed that hSef interacts and functionally colocalizes with EGFR in early
      endosomes in response to EGF stimulation. Importantly, we demonstrated that
      overexpression of hSef attenuates EGFR degradation and potentiates EGF-mediated
      mitogen-activated protein kinase (MAPK) signaling by interfering EGFR
      trafficking. Finally, our data showed that, with overexpression of hSef, elevated
      levels of Erk phosphorylation and differentiation of rat pheochromocytoma (PC12)
      cells occur in response to EGF stimulation. Taken together, these data suggest
      that hSef plays a positive role in the EGFR-mediated MAPK signaling pathway. This
      report, for the first time, reveals opposite roles for Sef in EGF and FGF
      signalings.

PMID- 18096369
TI  - No association between schizophrenia and polymorphisms of the PlexinA2 gene in
      Chinese Han Trios.

PMID- 18096370
TI  - Clozapine: toxicity vs. postmortem redistribution.

PMID- 18096371
TI  - Deficit of theory of mind in individuals at ultra-high-risk for schizophrenia.
AB  - BACKGROUND: Although a deficit in social cognition is regarded as an early
      indicator of schizophrenia, few studies have investigated social cognition in
      ultra-high-risk (UHR) individuals. METHODS: Our investigation involved subjects
      at UHR for psychosis (N=33) and an age- and IQ-matched healthy control (HC) group
      (N=36). Two types of theory of mind (ToM) tasks and a neuropsychological test
      battery were measured. RESULTS: Compared to the HC group, the UHR group performed
      significantly worse for ToM tasks, with the effect size at an intermediate level
      (0.64-0.68). Furthermore, the UHR group showed impaired performance in the
      executive and working memory tests, but not verbal memory tests. These deficits
      for ToM tests observed in the UHR group were significantly correlated with set
      shifting tasks. CONCLUSIONS: Deficits in social cognition may be modest at the
      prodromal stage of schizophrenia and may be attributed to prefrontal dysfunction.
      To prevent or delay transition to psychosis, there is a need for specific
      preventive strategies targeting social functioning for the UHR group.

PMID- 18096372
TI  - Maltose transport in Lactobacillus casei and its regulation by inducer exclusion.
AB  - Transport of maltose in Lactobacillus casei BL23 is subject to regulation by
      inducer exclusion. The presence of glucose or other rapidly metabolized carbon
      sources blocks maltose transport by a control mechanism that depends on the
      phosphorylation of the HPr protein at serine residue 46. We have identified the
      L. casei gene cluster for maltose/maltodextrin utilization by sequence analysis
      and mutagenesis. It is composed of genes coding for a transcriptional regulator,
      oligosaccharide hydrolytic enzymes, an ABC transporter (MalEFGK2) and the enzymes
      for the metabolism of maltose or the degradation products of maltodextrins:
      maltose phosphorylase and beta-phospho-glucomutase. These genes are induced by
      maltose and repressed by the presence of glucose via the catabolite control
      protein A (CcpA). A mutant strain was constructed which expressed the hprKV267F
      allele and therefore formed large amounts of P-Ser-HPr even in the absence of a
      repressive carbon source. In this mutant, transport of maltose was severely
      impaired, whereas transport of sugars not subject to inducer exclusion was not
      changed. These results strengthen the idea that P-Ser-HPr controls inducer
      exclusion and make the maltose system of L. casei a suitable model for studying
      this process in Firmicutes.

PMID- 18096373
TI  - Prevalence of antimicrobial resistance among uropathogens causing acute
      uncomplicated cystitis in female outpatients in South Korea: a multicentre study
      in 2006.
AB  - The Korean Association of Urogenital Tract Infection and Inflammation (KAUTII)
      conducted a survey of the antimicrobial susceptibility patterns of uropathogens
      responsible for female acute uncomplicated cystitis in South Korea in 2006.
      KAUTII has already reported similar data in 2002, which are compared with the
      results of the present study. This study was carried out with the participation
      of 22 hospitals in South Korea. A total of 301 isolates were obtained from female
      outpatients with acute uncomplicated cystitis. The antimicrobial susceptibilities
      to commonly prescribed drugs were determined. The most prevalent causative
      organism was Escherichia coli (71.1%), followed by enterococci (13.0%), coagulase
      negative staphylococci (5.3%) and other species of Enterobacteriaceae (10.6%).
      Among all Enterobacteriaceae isolates, 31.4% were susceptible to ampicillin,
      52.3% to ampicillin/sulbactam, 97.6% to piperacillin/tazobactam, 78.9% to
      ciprofloxacin, 80.3% to gatifloxacin, 86.8% to cefazolin, 99.6% to amikacin,
      80.5% to gentamicin, 81.1% to tobramycin and 73.9% to
      trimethoprim/sulfamethoxazole (TMP/SMX). The resistance rates of E. coli to
      ciprofloxacin and gatifloxacin were 23.4% and 21.8%, respectively, and 12 (11.8%)
      of 102 suspected strains were confirmed as producing extended-spectrum beta
      lactamase (ESBL). All the ESBL-producing strains were also resistant to
      fluoroquinolones. Enterobacteriaceae were highly susceptible to
      piperacillin/tazobactam and amikacin (>97%). There was a small increase in
      susceptibility to TMP/SMX (73.9%) compared with the same study in 2002 (62.1%).
      Similar to 2002, the high prevalence of resistance to ampicillin,
      ampicillin/sulbactam and TMP/SMX still exists. The increasing number of ESBL
      producing or fluoroquinolones-resistant strains remains a serious clinical
      problem in South Korea.

PMID- 18096374
TI  - Latent tree models and diagnosis in traditional Chinese medicine.
AB  - OBJECTIVE: TCM (traditional Chinese medicine) is an important avenue for disease
      prevention and treatment for the Chinese people and is gaining popularity among
      others. However, many remain skeptical and even critical of TCM because of a
      number of its shortcomings. One key shortcoming is the lack of objective
      diagnosis standards. We endeavor to alleviate this shortcoming using machine
      learning techniques. METHOD: TCM diagnosis consists of two steps, patient
      information gathering and syndrome differentiation. We focus on the latter. When
      viewed as a black box, syndrome differentiation is simply a classifier that
      classifies patients into different classes based on their symptoms. A fundamental
      question is: do those classes exist in reality? To seek an answer to the question
      from the machine learning perspective, one would naturally use cluster analysis.
      Previous clustering methods are unable to cope with the complexity of TCM. We
      have therefore developed a new clustering method in the form of latent tree
      models. We have conducted a case study where we first collected a data set about
      a TCM domain called kidney deficiency and then used latent tree models to analyze
      the data set. RESULTS: Our analysis has found natural clusters in the data set
      that correspond well to TCM syndrome types. This is an important discovery
      because (1) it provides statistical validation to TCM syndrome types and (2) it
      suggests the possibility of establishing objective and quantitative diagnosis
      standards for syndrome differentiation. In this paper, we provide a summary of
      research work on latent tree models and report the aforementioned case study.

PMID- 18096375
TI  - Protection of pancreatic beta-cells: is it feasible?
AB  - Hyperglycemia, which is the biochemical hallmark of type 2 diabetes, mainly
      results from insulin resistance and beta-cell dysfunction. However, the latter is
      crucial in the development of the disease because diabetes cannot occur without
      an impairment of insulin secretion. Beta-cell failure is also responsible for
      progressive loss of metabolic control in type 2 diabetic patients and the
      eventual need for insulin treatment. An impairment of beta-cell function can be
      detected in several ways and can be observed already in pre-diabetic individuals.
      Histopathology studies documented that beta-cell volume is reduced in pre
      diabetes and, to a greater extent, in type 2 diabetes mainly because the
      apoptotic rate of beta-cells is increased whereas neogenesis is intact. All anti
      diabetic agents can improve, directly or indirectly, beta-cell function. However,
      only PPAR-gamma agonists and incretin-mimetic agents seem to have favorable
      effects on beta-cell morphology and volume. Many trials showed that type 2
      diabetes can be prevented but few of them directly addressed the issue of beta
      cell protection by the intervention used in the study. It is reasonable to
      conclude that in these trials diabetes prevention, which was based on the use of
      lifestyle changes (diet and/or exercise) or different drugs (tolbutamide,
      acarbose, metformin, glitazones, bezafibrate, orlistat, angiotensin converting
      enzyme inhibitors, angiotensin II receptor blockers or pravastatin), depended
      also, or mainly, on a protection of the beta-cells but in most studies data on
      insulin secretion are not available or are insufficient to draw firm conclusions.
      The mechanisms of beta-cell protection in these trials, if any, remain unknown.
      They could be various and likely included reduced glucotoxicity, lipotoxicity,
      insulin resistance, inflammation, oxidant stress and/or apoptosis, an
      amelioration of islet blood flow and/or favorable changes in cation balance
      within the islets. Contrasting the decline and the eventual failure of beta-cells
      is crucial in preventing type 2 diabetes as well as in changing the natural
      history of the disease, when it occurs. The protection can be achieved in several
      ways but any strategy should include a change in lifestyle in order to generate a
      healthier islet milieu. Among anti-diabetic drugs, PPAR-gamma agonists and
      incretin-mimetic agents are the most promising in the protection. Among other
      drugs, inhibitors of the renin-angiotensin system might play a significant role.
      The increased worldwide diffusion of type 2 diabetes and the progressive loss of
      metabolic control in affected patients are clear demonstrations that the
      strategies to protect the beta-cells implemented so far, if any, were largely
      inadequate. Anti-diabetic agents targeting the intimate mechanisms of beta-cell
      damage might change the scenario in the near future.

PMID- 18096377
TI  - Mercury reduction studies to facilitate the thermal decontamination of phosphor
      powder residues from spent fluorescent lamps.
AB  - This work investigates the thermal release of mercury from phosphor powder of
      spent fluorescent lamps. The treatment conditions and the ability of various
      reducing agents (primarily sodium borohydride) to lower the overall heating
      temperature required to improve the release of Hg have been evaluated. Hg species
      in samples were monitored in a thermal desorption atomic absorption spectrometer
      system, and total mercury was analyzed in a cold vapor atomic absorption
      spectrometer. Sodium borohydride was the best reducing agent among the ones
      studied. However, citric acid presented a high capacity to weaken mercury bonds
      with the matrix. When the sample was crushed with sodium borohydride for 40 min
      in a mass ratio of 10:1 (sample:reducing agent) and submitted to thermal
      treatment at 300 degrees C for 2 h, the concentration of mercury in a phosphor
      powder sample with 103 mg kg(-1) of mercury reached 6.6 mg kg(-1).

PMID- 18096378
TI  - Oxygen-reducing enzyme cathodes produced from SLAC, a small laccase from
      Streptomyces coelicolor.
AB  - The bacterially-expressed laccase, small laccase (SLAC) of Streptomyces
      coelicolor, was incorporated into electrodes of both direct electron transfer
      (DET) and mediated electron transfer (MET) designs for application in biofuel
      cells. Using the DET design, enzyme redox kinetics were directly observable using
      cyclic voltammetry, and a redox potential of 0.43 V (SHE) was observed. When
      mediated by an osmium redox polymer, the oxygen-reducing cathode retained maximum
      activity at pH 7, producing 1.5 mA/cm2 in a planar configuration at 900 rpm and
      40 degrees C, thus outperforming enzyme electrodes produced using laccase from
      fungal Trametes versicolor (0.2 mA/cm2) under similar conditions. This
      improvement is directly attributable to differences in the kinetics of SLAC and
      fungal laccases. Maximum stability of the mediated SLAC electrode was observed at
      pH above the enzyme's relatively high isoelectric point, where the anionic enzyme
      molecules could form an electrostatic adduct with the cationic mediator. Porous
      composite SLAC electrodes with increased surface area produced a current density
      of 6.25 mA/cm2 at 0.3 V (SHE) under the above conditions.

PMID- 18096379
TI  - Course and prognosis of basaloid squamous cell carcinoma of the head and neck: a
      case-control study of 62 patients.
AB  - OBJECTIVE: To describe the natural history and evaluate the prognosis of basaloid
      squamous cell carcinoma (BSCC) of the upper aero-digestive tract as compared to
      the usual squamous cell carcinoma (SCC). MATERIALS AND METHODS: Sixty-two
      patients with BSCC and 62 patients with SCC were matched with regards to TNM
      classification, localisation and therapeutic modalities. Histological criteria,
      follow-up and 5-year survival were compared among the two groups. RESULTS:
      Survival rates were significantly higher in patients with SCC as compared to
      patients with BSCC. The rate of distant metastasis was six times higher in cases
      of BSCC, which was the major cause of mortality. CONCLUSION: This study reveals
      that BSCC has distinct histo-pathologic features and an aggressive clinical
      course, justifying its consideration as a separate entity with poor prognosis.
      The authors propose to systematically perform a chest CT-scan and FDG-PET to rule
      out early distant metastasis and to include adjuvant chemotherapy in treatment
      protocols.

PMID- 18096380
TI  - Synthesis and decoloring properties of sodium humate/poly (N-isopropylacrylamide)
      hydrogels.
AB  - A series of novel sodium humate/poly(N-isopropylacrylamide) (SH/PNIPA) hydrogels
      were synthesized by solution polymerization. The swelling and decoloring
      properties of SH/PNIPA hydrogels were also examined. Experiment results show that
      there exist hydrogen-bonding interactions between SH and PNIPA in the SH/PNIPA
      hydrogels network, which are not strong enough to disrupt the aggregation of
      dehydrated PNIPA chains at phase transition temperature, leading to the same
      volume phase transition temperature as pure PNIPA hydrogel. The adsorption and
      desorption of methylene blue (MB) for the hydrogels were influenced by
      temperature, initial MB concentration and SH amount. Low temperature favors the
      adsorption and desorption of MB. Appropriate SH amount of the hydrogels is
      crucial for the adsorption and desorption of MB. The maximum adsorption capacity
      was 10.8 mg MB per gram of SH/PNIPA gel.

PMID- 18096381
TI  - Characterization of the degree of polymerization of xylooligomers produced by
      flowthrough hydrolysis of pure xylan and corn stover with water.
AB  - Mechanisms that control xylan removal during pretreatment of lignocellulosic
      biomass are not well understood. For example, although hemicellulose hydrolysis
      is virtually always assumed to follow first-order homogeneous kinetics, the
      increase in xylan removal with flow rate for flowthrough pretreatment systems is
      inconsistent with the predictions for such models, and better information is
      needed to understand the causes of such discrepancies. Thus, new methods were
      developed to follow the fate of xylooligomers with degrees of polymerization of
      up to 30, a range not possible before, for water-only flowthrough pretreatment of
      oat spelt xylan and corn stover for temperatures of 200-240 degrees C. Material
      balances based on the oligomer release profiles produced by batch and flowthrough
      operations could be closed, suggesting the methods were quite accurate. However,
      the results also showed that increasing the flow rate from 0 to 2 and then 25
      mL/min affected the size distribution of the xylan oligomers (DP<30) released
      from corn stover but not from oat spelt xylan and also increased overall
      hemicellulose sugar solubilization. One explanation for these difference is that
      lignin and lignin-xylan compounds in particular play an important role in the
      hydrolysis of lignocellulosic biomass.

PMID- 18096382
TI  - Biosorption of heavy metals from aqueous solutions with tobacco dust.
AB  - A typical lignocellulosic agricultural residue, namely tobacco dust, was
      investigated for its heavy metal binding efficiency. The tobacco dust exhibited a
      strong capacity for heavy metals, such as Pb(II), Cu(II), Cd(II), Zn(II) and
      Ni(II), with respective equilibrium loadings of 39.6, 36.0, 29.6, 25.1 and 24.5mg
      of metal per g of sorbent. Moreover, the heavy metals loaded onto the biosorbent
      could be released easily with a dilute HCl solution. Zeta potential and surface
      acidity measurements showed that the tobacco dust was negatively charged over a
      wide pH range (pH>2), with a strong surface acidity and a high OH(-) adsorption
      capacity. Changes in the surface morphology of the tobacco dust as visualized by
      atomic force microscopy suggested that the sorption of heavy metal ions on the
      tobacco could be associated with changes in the surface properties of the dust
      particles. These surface changes appeared to have resulted from a loss of some of
      the structures on the surface of the particles, owing to leaching in the acid
      metal ion solution. However, Fourier transform infrared spectroscopy (FTIR)
      showed no substantial change in the chemical structure of the tobacco dust
      subjected to biosorption. The heavy metal uptake by the tobacco dust may be
      interpreted as metal-H ion exchange or metal ion surface complexation adsorption
      or both.

PMID- 18096383
TI  - Ethanol production from maize silage as lignocellulosic biomass in anaerobically
      digested and wet-oxidized manure.
AB  - In this communication, pretreatment of the anaerobically digested (AD) manure and
      the application of the pretreated AD manure as liquid medium for the simultaneous
      saccharification and fermentation (SSF) were described. Furthermore, fermentation
      of pretreated maize silage and wheat straw was investigated using 2l bioreactors.
      Wet oxidation performed for 20 min at 121 degrees C was found as the most
      suitable pretreatment conditions for AD manure. High ammonia concentration and
      significant amount of macro- and micro-nutrients in the AD manure had a positive
      influence on the ethanol fermentation. No extra nitrogen source was needed in the
      fermentation broth. It was shown that the AD manure could successfully substitute
      process water in SSF of pretreated lignocellulosic fibres. Theoretical ethanol
      yields of 82% were achieved, giving 30.8 kg ethanol per 100 kg dry mass of maize
      silage.

PMID- 18096384
TI  - An alkali-stable enzyme with laccase activity from entophytic fungus and the
      enzymatic modification of alkali lignin.
AB  - Mycelia Sterilia YY-5, an entophytic fungus, was isolated from Rhus chinensis
      Mill and its extracellular enzyme had a higher laccase activity (MS-Lac). After
      been purified by anion exchange and gel filtration chromatography, MS-Lac, which
      had a molecular mass of 45 kDa, was found to be an alkali-stable enzyme with an
      optimum pH of 10.0 and capable of retaining 80% activity after incubation for 72
      h with syringaldazine as substrate. It was also found that syringaldazine had a
      higher affinity than 2,2'-azino-bis-(3-ethylbenzothiazoline)-6-sulphonate (ABTS)
      as substrate for MS-Lac, which was determined in sodium phosphate buffer (pH 6.0,
      0.1M) at 30 degrees C. Meanwhile, the lignin modification, catalyzed by MS-Lac,
      indicated that it could oxidize the phenolic hydroxyl, side chain substituent or
      carbonyl group of spruce alkali lignin in cetyltrimethylammonium bromide (CTAB)
      reversed micelles (20 mM, pH 6.0, W/O=40) and steam-exploded wheat straw alkali
      lignin in NaOH solution (20 mM, pH 10.0).

PMID- 18096385
TI  - Identification of ACE pharmacophore in the phosphonopeptide metabolite K-26.
AB  - The naturally occurring phosphonotripeptide K-26 is a potent angiotensin
      converting enzyme (ACE) inhibitor containing an alpha-amino phosphonic acid
      analogue of tyrosine. Previous studies have demonstrated that canonical peptide
      analogues of K-26 are micromolar inhibitors of ACE. To ascertain the structure
      activity relationships in this class of ACE inhibitory natural products, K-26 and
      eight analogues were chemically synthesized and evaluated. Phosphonyl
      substitution was found to be the critical determinant of activity, resulting in a
      1500-fold increase in ACE inhibition versus carboxyl analogues. Secondarily, the
      absolute configuration of the terminal alpha-amino phosphonate and N-acetylation
      were found to significantly modulate ACE inhibitory activity.

PMID- 18096386
TI  - From rigid cyclic templates to conformationally stabilized acyclic scaffolds.
      Part I: the discovery of CCR3 antagonist development candidate BMS-639623 with
      picomolar inhibition potency against eosinophil chemotaxis.
AB  - Conformational analysis of trans-1,2-disubstituted cyclohexane CCR3 antagonist 2
      revealed that the cyclohexane linker could be replaced by an acyclic syn-alpha
      methyl-beta-hydroxypropyl linker. Synthesis and biological evaluation of mono-
      and disubstituted propyl linkers support this conformational correlation. It was
      also found that the alpha-methyl group to the urea lowered protein binding and
      that the beta-hydroxyl group lowered affinity for CYP2D6. Ab initio calculations
      show that the alpha-methyl group governs the spatial orientation of three key
      functionalities within the molecule. alpha-Methyl-beta-hydroxypropyl urea 31 with
      a chemotaxis IC(50)=38 pM for eosinophils was chosen to enter clinical
      development for the treatment of asthma.

PMID- 18096387
TI  - Synthesis and characterization of 8-ethynyl-1,3-dihydro-benzo[b][1,4]diazepin-2
      one derivatives: part 2. New potent non-competitive metabotropic glutamate
      receptor 2/3 antagonists.
AB  - A series of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives was evaluated as
      non-competitive mGluR2/3 antagonists. Replacement of a cyano group by a five
      membered heterocycle produced compounds inhibiting the binding of [(3)H]-LY354740
      to rat mGluR2 with low nanomolar affinity and consistent functional effect at
      both mGluR2 and mGluR3. Further modification to improve the physicochemical
      properties led eventually to compounds with the ability to reverse LY354740
      mediated inhibition of field excitatory postsynaptic potentials in the rat
      dentate gyrus.

PMID- 18096388
TI  - Patient safety and job-related stress: a focus group study.
AB  - This study focused on work-related stress among nurses working with critically
      ill patients. The aim of the study was to examine the effects of work-related
      stress with regard to patient safety. The study uses a qualitative design based
      on focus group interviews with nurses who work with acute, critically ill
      patients in hospitals. Two regional hospitals were chosen. Inclusion criteria for
      the focus group panels included the following: nurses with advanced training in
      anesthesiology, intensive care, or operating-room nursing. Twenty-three nurses
      were chosen and they were divided into four groups. This study shows that a
      demanding work environment together with minimal control and social support from
      colleagues results in increased stress that can often have an effect on patient
      safety.

PMID- 18096389
TI  - Invasive in vivo measurement of rear-, mid- and forefoot motion during walking.
AB  - The aim of this work was to use bone anchored external markers to describe the
      kinematics of the tibia, fibula, talus, calcaneus, navicular, cuboid, medial
      cuneiform, first and fifth metatarsals during gait. Data were collected from six
      subjects. There was motion at all the joints studied. Movement between the talus
      and the tibia showed the expected predominance of sagittal plane motion, but the
      talocalcaneal joint displayed greater variability than expected in its motion.
      Movement at the talonavicular joint was greater than at the talocalcaneal joint
      and motion between the medial cuneiform and navicular was far greater than
      expected. Motion between the first metatarsal and the medial cuneiform was less
      than motion between the fifth metatarsal and cuboid. Overall the data
      demonstrated the complexity of the foot and the importance of the joints distal
      to the rearfoot in its overall dynamic function.

PMID- 18096390
TI  - Spinal stability is improved by inducing a lumbar lordosis in boys with Duchenne
      Muscular Dystrophy: a pilot study.
AB  - The development of scoliosis in boys with Duchenne Muscular Dystrophy (DMD) is a
      significant, morbid event in the progression of the disease caused by progressive
      spinal musculature weakness. As an alternative to muscle activity, the spine can
      also be stabilised by locking the articular facet joints, which is achieved when
      the body is supported on a seat tilted anteriorly using a 'wedge', of the kind
      commonly recommended for low back pain. We tested spinal stability when using a
      seat tilted 15 degrees anteriorly in eight boys with DMD, without significant
      scoliosis, by measuring the ability to support a lateral load applied to the
      thorax through a sling and hawser. All eight boys tolerated lateral loading
      better with wedged seating and were able to support an average additional load of
      95 g per kilogram of body weight compared to normal seating. Lateral load bearing
      was improved in 10 normal control boys by an average of 40 g per kilogram of body
      weight. These encouraging pilot findings indicate that there is a need for
      further studies on the effectiveness of passive mechanical factors in spinal
      stabilisation to delay the development of scoliosis in boys with DMD.

PMID- 18096391
TI  - Mass spectrometry-based proteomics of fungal wall glycoproteins.
AB  - The manifold functions of fungal wall glycoproteins include maintenance of cell
      wall integrity, homotypic and heterotypic adhesion, biofilm formation,
      acquisition of iron and sterols, protein degradation and coping with oxidative
      stress. Transcriptome studies indicate that the expression levels of most cell
      wall glycoproteins can vary widely and are tightly controlled. However, owing to
      their complex and variable glycosylation, fungal wall glycoproteins are difficult
      to analyze using traditional proteomics approaches. Recent advances in mass
      spectrometry-based proteomics have enabled rapid and sensitive identification and
      quantitation of fungal wall glycoproteins; this will be particularly useful for
      studying the dynamics of the subproteome of fungal wall glycoproteins, and for
      the development of novel vaccines and diagnostic tools.

PMID- 18096392
TI  - New insights into animal pathogenic oomycetes.
AB  - Many species of oomycetes cause economic and environmental damage owing to their
      ability to infect a range of plants and animals. Although research on plant
      pathogenic oomycetes has flourished in recent years, the animal pathogenic
      oomycetes have received less attention. This is unfortunate because several
      species are responsible for devastating diseases in aquaculture and natural
      ecosystems and proper treatments are not available or are limited. Therefore,
      momentum is being created to revive research into this neglected group of
      pathogens. Here, we discuss the latest developments in our current understanding
      of the biology, host-pathogen interactions and environmental and economical
      impact of the animal pathogenic oomycetes and review the recent advances in this
      emerging field.

PMID- 18096393
TI  - Synthesis and biological evaluation of 2-alkylaminoethyl-1,1-bisphosphonic acids
      against Trypanosoma cruzi and Toxoplasma gondii targeting farnesyl diphosphate
      synthase.
AB  - The effect of a series of 2-alkylaminoethyl-1,1-bisphosphonic acids against
      proliferation of the clinically more relevant form of Trypanosoma cruzi, the
      etiologic agent of American trypanosomiasis (Chagas' disease), and against
      tachyzoites of Toxoplasma gondii has been studied. Most of these drugs exhibited
      an extremely potent inhibitory action against the intracellular form of T. cruzi,
      exhibiting IC(50) values at the low micromolar level. This cellular activity was
      associated with a strong inhibition of the enzymatic activity of T. cruzi
      farnesyl diphosphate synthase (TcFPPS), which constitutes a valid target for
      Chagas' disease chemotherapy. Compound 17 was an effective agent against
      amastigotes exhibiting an IC(50) value of 0.84 microM, while this compound showed
      an IC(50) value of 0.49 microM against the target enzyme TcFPPS. Interestingly,
      compound 19 was very effective against both T. cruzi and T. gondii exhibiting
      IC(50) values of 4.1 microM and 2.6 microM, respectively. In this case, 19
      inhibited at least two different enzymes of T. cruzi (TcFPPS and solanesyl
      diphosphate synthase (TcSPPS); 1.01 microM and 0.25 microM, respectively), while
      it inhibited TgFPPS in T. gondii. In general, this family of drugs was less
      effective against the activity of T. cruzi SPPS and against T. gondii growth in
      vitro. As bisphosphonate-containing compounds are FDA-approved drugs for the
      treatment of bone resorption disorders, their potential low toxicity makes them
      good candidates to control tropical diseases.

PMID- 18096394
TI  - Diazen-1-ium-1,2-diolated and nitrooxyethyl nitric oxide donor ester prodrugs of
      anti-inflammatory (E)-2-(aryl)-3-(4-methanesulfonylphenyl)acrylic acids:
      synthesis, cyclooxygenase inhibition, and nitric oxide release studies.
AB  - A new group of hybrid nitric oxide-releasing anti-inflammatory drugs wherein an
      O(2)-acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate (11a-d), or
      2-nitrooxyethyl (12a-d), (*)NO-donor moiety is attached directly to the
      carboxylic acid group of (E)-3-(4-methanesulfonylphenyl)-2-(phenyl)acrylic acids
      were synthesized. The 2-nitrooxyethyl ester prodrugs (12a-d) all exhibited in
      vitro inhibitory activity against the cyclooxygenase-2 (COX-2) isozyme
      (IC(50)=0.07-2.8 microM range). All compounds released a low amount of (*)NO upon
      incubation with phosphate buffer (PBS) at pH 7.4 (1.0-4.8% range). In comparison,
      the percentage (*)NO released was significantly higher (76.2-83.0% range) when
      the diazen-1-ium-1,2-diolate ester prodrugs were incubated in the presence of rat
      serum, or moderately higher (7.6-10.1% range) when the nitrooxyethyl ester
      prodrugs were incubated in the presence of L-cysteine. These incubation studies
      suggest that both (*)NO and the parent anti-inflammatory (E)-3-(4
      methanesulfonylphenyl)-2-(phenyl)acrylic acid would be released upon in vivo
      cleavage by non-specific serum esterases in the case of the diazen-1-ium-1,2
      diolate esters (11a-d), or interaction with systemic thiols in the case of the
      nitrate esters (12a-d). O(2)-Acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium
      1,2-diolate (E)-3-(4-methanesulfonylphenyl)-2-phenylacrylate (11a) released 83%
      of the theoretical maximal release of 2 molecules of (*)NO/molecule of the parent
      hybrid ester prodrug upon incubation with rat serum. Hybrid ester anti
      inflammatory/(*)NO donor prodrugs offer a potential drug design concept targeted
      toward the development of anti-inflammatory drugs that are devoid of adverse
      ulcerogenic and/or cardiovascular effects.

PMID- 18096395
TI  - Dose-limited spectroscopic imaging of soft materials by low-loss EELS in the
      scanning transmission electron microscope.
AB  - Spectroscopic imaging in the scanning transmission electron microscope (STEM)
      using spatially resolved electron energy-loss spectroscopy (EELS) provides one of
      the few ways to quantitatively measure the real-space nanoscale morphology of
      soft materials such as polymers and biological tissue. This paper describes the
      basic principles of this technique and outlines some of the important attributes
      that define the achievable spatial resolution. Many soft materials can be
      differentiated from each other as well as from solvents based on their EELS
      fingerprints. Applying a multiple least squares (MLS) fitting algorithm using
      such spectral fingerprints to analyze spatially resolved spectrum datasets
      enables the quantitative mapping of the different components in a specimen.
      However, in contrast to TEM studies of many inorganic materials where the spatial
      resolution is limited principally by the spherical aberration of the objective
      lens, the spatial resolution associated with the imaging of radiation-sensitive
      soft materials is limited by the total electron dose to which they can be exposed
      before suffering irrevocable chemical or structural damage. The Rose criterion
      provides a simple guide to enhance the so-called dose-limited spatial resolution
      relevant to soft-materials imaging. By using the low-loss portion of an EELS
      spectrum where the inelastic scattering cross-sections are highest together with
      improvements in data-collection efficiency and post-acquisition data processing,
      the dose-limited resolution in spectrum images of solvated polymers has moved
      into the sub 10nm regime. This resolution is sufficient to solve important
      applications-oriented problems associated with hetero interfaces, nanoscale
      mixing, and nanophase separation.

PMID- 18096396
TI  - Treatment options for severe cardiac amyloidosis: heart transplantation combined
      with chemotherapy and stem cell transplantation for patients with AL-amyloidosis
      and heart and liver transplantation for patients with ATTR-amyloidosis.
AB  - OBJECTIVE: Cardiac amyloidosis (CA) is associated with a poor prognosis and a
      survival rate of less than 30% 2 years after clinical manifestation. Considered
      as a semi-malignant disease, CA is often a contraindication for HTx; however,
      depending on the type of CA, there are excellent treatment regimes that can be
      combined with HTx. In AL-amyloidosis, chemotherapy and stem cell transplantation
      are necessary and in TTR-amyloidosis, where the liver is the source of the
      pathologic protein, liver transplantation is recommended after HTx. METHODS AND
      RESULTS: More than 60 patients with AL-amyloidosis and more than 25 patients with
      ATTR-amyloidosis have been investigated at our centre. Eighteen patients showed
      signs of end-stage heart failure. Four patients died within 1 month after listing
      for HTx. Seven patients with AL (mean age 41.8 years) and five patients with ATTR
      amyloidosis (mean age 42.6 years) were successfully transplanted with an actual
      survival rate of 91.6%. One patient died 8 months after HTx due to infection.
      Five AL patients received chemotherapy and SCT and one ATTR patient was liver
      transplanted. Three AL patients showed complete remission of amyloidosis.
      CONCLUSIONS: Cardiac amyloidosis is a potentially curative disease after HTx when
      combined with either chemotherapy and SCT or LiverTx depending on the type of the
      amyloidosis. Due to the natural course of the disease, urgent HTx after cardiac
      manifestation is mandatory. With this approach, excellent survival rates and even
      remission of the underlying disease is possible.

PMID- 18096397
TI  - Fibrin sealant in coronary artery bypass grafting surgery; reflection on risk and
      benefit.

PMID- 18096398
TI  - Role of positron emission tomography in mediastinal lymphatic staging of non
      small cell lung cancer.
AB  - OBJECTIVE: Positron emission tomography (PET) is used increasingly in staging of
      non-small cell lung cancer (NSCLC) as a non-invasive tool. The role of the PET in
      mediastinal lymphatic staging of NSCLC is not clear. We aimed to demonstrate the
      efficacy of PET in determining mediastinal lymphatic metastasis by comparing the
      results of PET with mediastinoscopy. PATIENTS AND METHODS: We performed PET
      preoperatively in 170 patients with clinically operable NSCLC between 2004 and
      2006. Stations defined as metastasis by PET (SUV(max) >2.5) were recorded.
      Mediastinoscopy was performed initially in all patients and a total of 687
      stations which can be reached with mediastinoscope were sampled (mean 4.04).
      Forty-three patients with mediastinal metastasis were referred to the oncology
      clinic for chemotherapy while lung resection and complete mediastinal lymphatic
      dissection through thoracotomy was performed in the remaining 127 patients.
      Involvement of mediastinal lymph nodes was verified to compare the sensitivity
      and specificity of mediastinoscopy and the related PET results. RESULTS:
      Histopathologic classification of the tumors revealed 79 squamous carcinomas and
      58 adenocarcinomas. False positivity rate of PET was 26% (95% CI: 14-38), false
      negativity was 25% (95% CI: 18-33), sensitivity was 74% (95% CI: 63-86),
      specificity was 73% (95% CI: 66-82) and accuracy was 74% in mediastinal staging.
      Negative predictive value of mediastinoscopy was 94% (95% CI: 89-98), positive
      predictive value 100%, sensitivity 84% (95% CI: 74-94), specificity 100% and
      accuracy was 95%. CONCLUSION: PET results do not provide acceptable accuracy
      rates. Mediastinoscopy still remains the gold standard for mediastinal staging of
      NSCLC, although it cannot reach to all the mediastinal stations.

PMID- 18096399
TI  - The surgical management of giant left atrium.
AB  - Giant left atrium (GLA) is a condition defined when the left atrial diameter
      exceeds 65 mm. GLA is commonly associated with mitral valve regurgitation due to
      excess intracavitary pressure resulting in strain and dilation of the left atrial
      chamber. The mechanism of lone GLA remains unknown but is possibly related to
      inherent weakening of the atrial wall tissue. The enlarged left atrium leads to
      expansion of left atrial volume, which in turn can place pressure on the main
      bronchus, lung, and left ventricle with corresponding cardiopulmonary
      embarrassment. Because GLA can increase the risk of sudden death, its existence
      merits careful evaluation and surgical intervention when needed. Careful review
      of the literature reveals that the presence of GLA in the context of severe
      mitral valve regurgitation with or without atrial fibrillation is the most common
      indication for surgical intervention. Indications for intervening on lone GLA are
      rare except when compressive symptoms manifest. Partial resection of inferior and
      or superior left atrial wall is the most common surgical technique. With the
      evolution of atrial fibrillation surgery, atrial size matters and is determinant
      of long term performance following successful ablation. Surgical management of
      GLA achieves good clinical outcome with respect to cardiopulmonary performance
      including restoration of sinus rhythm among patients suffering from atrial
      fibrillation. Surgeons should be aware of current modalities for atrial volume
      reduction when indicated to retain the function and structure of the left atrium.

PMID- 18096400
TI  - Molecular characterization of woodchuck type I interferons and their expression
      by woodchuck peripheral blood lymphocytes.
AB  - Interferon (IFN)-alpha and -beta are important antiviral mediators. IFN-alpha is
      widely used for the treatment of chronic hepatitis B. In our previous studies, a
      subtype of woodchuck IFN-alpha (wIFN-alpha) was characterized and has been shown
      to be active in suppressing the replication of woodchuck hepatitis virus (WHV) in
      vitro and vivo. Here, we refined the analysis of the IFN-alpha/beta system of the
      woodchuck and studied the expression of wIFN-alpha/beta in peripheral blood
      lymphocytes (PBLs) from naive and WHV-infected woodchucks. A number of wIFN-alpha
      genes were sequenced and could be classified into 10 subtypes and 3 pseudotypes.
      The biological activity of different subtypes of wIFN-alpha was demonstrated by
      their ability to protect woodchuck cells against encephalomyocarditis virus
      infection and to induce MxA expression in woodchuck cells. Additionally, a
      partial sequence of wIFN-beta was characterized. A subtyping method for wIFN
      alpha based on restriction length polymorphism analysis was developed. Further,
      the expression of wIFN by woodchuck PBLs after stimulation with polyI/C was
      investigated. The maximal production of wIFN by woodchuck PBLs occurred within
      the first 48 h after addition poly I/C. The wIFN-alpha subtypes 1, 4, and 5 were
      found to be produced by poly I/C-stimulated woodchuck PBLs, indicating a
      selective expression of wIFN-alpha subtypes. PBLs from chronically WHV-infected
      woodchucks showed a reduced ability to produce wIFN when stimulated with poly
      I/C. The results suggest that woodchucks with chronic WHV infection have impaired
      immunological responses to poly I/C.

PMID- 18096401
TI  - Identification of an alternative translation initiation site for the Pantoea
      ananatis lycopene cyclase (crtY) gene in E. coli and its evolutionary
      conservation.
AB  - Previous sequence analyses of the lycopene cyclase gene (crt Y) from Pantoea
      ananatis revealed that translation of its protein product in Escherichia coli
      began at the ATG start codon. We found, however, that this enzyme could also be
      produced in E. coli without the ATG start codon present. Results of experiments
      using crt Y mutants revealed that a GTG (Val) sequence, located in-frame and 24
      bp downstream of the ATG, could act as a potential start codon. Additionally, a
      point-mutated GTA (Val), replaced from alternative GTG start codon, also
      displayed its potential as a start codon although the strength as a translation
      initiation codon was considerably weak. This finding suggests that non-ATG
      codons, especially one base pairing with the anticodon (3'-UAC-5') in fMet-tRNA,
      might be also able to function as start codon in translation process.
      Furthermore, amino acid sequence alignment of lycopene cyclases from different
      sources suggested that a Val residue located within the N-terminus of these
      enzymes might be used as an alternative translation initiation site. In
      particular, presence of a conserved Asp, located in-frame and 12 bp upstream of
      potential start codon, supports this assumption in view of the fact that Asp (GAT
      or GAC) can function as part of the Shine-Dalgano sequence (AGGAGG).

PMID- 18096402
TI  - Electron tomographic analysis of cytoskeletal cross-bridges in the paranodal
      region of the node of Ranvier in peripheral nerves.
AB  - The node of Ranvier is a site for ionic conductances along myelinated nerves and
      governs the saltatory transmission of action potentials. Defects in the cross
      bridging and spacing of the cytoskeleton are a prominent pathological feature in
      diseases of the peripheral nerve. Electron tomography was used to examine
      cytoskeletal-cytoskeletal, membrane-cytoskeletal, and heterologous cell
      connections in the paranodal region of the node of Ranvier in peripheral nerves.
      Focal attachment of cytoskeletal filaments to each other and to the axolemma and
      paranodal membranes of the Schwann cell via narrow cross-bridges was visualized
      in both neuronal and glial cytoplasm. A subset of intermediate filaments
      associates with the cytoplasmic surfaces of supramolecular complexes of
      transmembrane structures that are presumed to include known and unknown
      junctional proteins. Mitochondria were linked to both microtubules and
      neurofilaments in the axoplasm and to neighboring smooth endoplasmic reticulum by
      narrow cross-bridges. Tubular cisternae in the glial cytoplasm were also linked
      to the paranodal glial cytoplasmic loop juxtanodal membrane by short cross
      bridges. In the extracellular matrix between axon and Schwann cell, junctional
      bridges formed long cylinders linking the two membranes. Interactions between
      cytoskeleton, membranes, and extracellular matrix associations in the paranodal
      region are likely critical not only for scaffolding, but also for intracellular
      and extracellular communication.

PMID- 18096404
TI  - Ultrastructural characterization of melanosomes of the human pathogenic fungus
      Fonsecaea pedrosoi.
AB  - Melanin is a complex polymer widely distributed in nature and has been described
      as an important virulence factor in pathogenic fungi. In the majority of fungi,
      the mechanism of melanin formation remains unclear. In Fonsecaea pedrosoi, the
      major etiologic agent of chromoblastomycosis, melanin is stored in intracellular
      vesicles, named melanosomes. This paper details the ultrastructural aspects of
      melanin formation, its storage and transportation to the cell wall in the human
      pathogenic fungus F. pedrosoi. In this fungus, melanin synthesis within
      melanosomes also begins with a fibrillar matrix formation, displaying
      morphological and structural features similar to melanosomes from amphibian and
      mammalian cells. Silver precipitation based on Fontana-Masson technique for
      melanin detection and immunocytochemistry showed that melanosome fuses with
      fungal cell membrane where the melanin is released and reaches the cell wall.
      Melanin deposition in the fungal cell wall occurs in concentric layers.
      Antibodies raised against F. pedrosoi melanin revealed the sites of melanin
      production and storage in the melanosomes. In addition, a preliminary description
      of the elemental composition of this organelle by X-ray microanalysis and
      elemental mapping revealed the presence of calcium, phosphorus and iron
      concentrated in its matrix, suggesting a new functional role for these organelles
      as iron storage compartments.

PMID- 18096403
TI  - Unique structures in a tumor herpesvirus revealed by cryo-electron tomography and
      microscopy.
AB  - Gammaherpesviruses, including the human pathogens Epstein-Barr virus and Kaposi's
      sarcoma-associated herpesvirus, are causative agents of lymphomas and other
      malignancies. The structural characterization of these viruses has been limited
      due to difficulties in obtaining adequate amount of virion particles. Here we
      report the first three-dimensional structural characterization of a whole
      gammaherpesvirus virion by an emerging integrated approach of cryo-electron
      tomography combined with single-particle cryo-electron microscopy, using murine
      gammaherpesvirus-68 (MHV-68) as a model system. We found that the MHV-68 virion
      consists of distinctive envelope and tegument compartments, and a highly
      conserved nucleocapsid. Two layers of tegument are identified: an inner tegument
      layer tethered to the underlying capsid and an outer, flexible tegument layer
      conforming to the overlying, pleomorphic envelope, consistent with the sequential
      viral tegumentation process inside host cells. Surprisingly, comparison of the
      MHV-68 virion and capsid reconstructions shows that the interactions between the
      capsid and inner tegument proteins are completely different from those observed
      in alpha and betaherpesviruses. These observations support the notion that the
      inner layer tegument across different subfamilies of herpesviruses has evolved
      significantly to confer specific characteristics related to viral-host
      interactions, in contrast to a highly conserved capsid for genome encapsidation
      and protection.

PMID- 18096405
TI  - Changes in EMG activity in the upper trapezius muscle due to local vibration
      exposure.
AB  - Exposure to vibration is suggested as a risk factor for developing neck and
      shoulder disorders in working life. Mechanical vibration applied to a muscle
      belly or a tendon can elicit a reflex muscle contraction, also called tonic
      vibration reflex, but the mechanisms behind how vibration could cause
      musculoskeletal disorders has not yet been described. One suggestion has been
      that the vibration causes muscular fatigue. This study investigates whether
      vibration exposure changes the development of muscular fatigue in the trapezius
      muscle. Thirty-seven volunteers (men and women) performed a sub-maximal isometric
      shoulder elevation for 3 min. This was repeated four times, two times with
      induced vibration and two times without. Muscle activity was measured before and
      after each 3-min period to look at changes in the electromyography parameters.
      The result showed a significantly smaller mean frequency decrease when performing
      the shoulder elevation with vibration (-2.51 Hz) compared to without vibration (
      4.04 Hz). There was also a slightly higher increase in the root mean square when
      exposed to vibration (5.7% of maximal voluntary contraction) compared to without
      (3.8% of maximal voluntary contraction); however, this was not statistically
      significant. The results of the present study indicate that short-time exposure
      to vibration has no negative acute effects on the fatiguing of upper trapezius
      muscle.

PMID- 18096406
TI  - The corpus callosum in schizophrenia-volume and connectivity changes affect
      specific regions.
AB  - The corpus callosum (CC) is of great interest for pathophysiological models of
      schizophrenia. Volume and structural integrity of the CC have been examined by
      volumetric and diffusion tensor imaging (DTI) studies, but results were not
      consistent across methods or studies. A possible explanation may be varying
      methodologies and accuracy of measurements based on a single slice or small
      regions of interest. In addition, none of the studies examined volume and
      diffusion values in the same group of patients, and thus the relationship between
      these anatomical measures is not clear. We used an automatic algorithm to segment
      seven midline slices of the CC from DTI images. We compared volume and the DTI
      measures fractional anisotropy (FA) and mean diffusivity (MD) in the CC and its
      subdivisions in the schizophrenia patients and matched controls. Patients had
      decreased volume, decreased FA and increased MD of the whole CC. The important
      novel finding is, however, that not all regions were equally affected by
      anatomical changes. The results emphasize the importance of using different
      methods in evaluation of white matter (WM) in schizophrenia to avoid false
      negative findings. In addition, the measures were highly correlated with each
      other, implying a common pathological process influencing FA, MD and volume of
      the CC. Although we cannot rule out other mechanisms affecting volume, FA and MD,
      converging evidence from cytoarchitectonic and genetic studies suggests that WM
      changes observed in schizophrenia may involve disintegration of healthy,
      functional axons and strengthening of aberrant connections resulting in increased
      severity of clinical symptoms.

PMID- 18096407
TI  - Functional re-recruitment of dysfunctional brain areas predicts language recovery
      in chronic aphasia.
AB  - Functional recovery in response to a brain lesion, such as a stroke, can even
      occur years after the incident and may be accelerated by effective rehabilitation
      strategies. In eleven chronic aphasia patients, we administered a short-term
      intensive language training to improve language functions and to induce cortical
      reorganization under rigorously controlled conditions. Overt naming performance
      was assessed during functional magnetic resonance imaging (fMRI) prior to and
      immediately after the language training. Regions of interest (ROIs) for
      statistical analyses were constituted by areas with individually determined
      abnormally high densities of slow wave generators (identified by
      magnetoencephalography prior to the language intervention) that clustered mainly
      in left perilesional areas. Three additional individually defined regions served
      to control for the specificity of the results for the selected respective target
      region: the homologue area of the individual patient's lesion, the mirror image
      of the delta ROI in the right hemisphere and left hemispheric regions that did
      not produce a significant amount of slow wave activity. Treatment-induced changes
      of fMRI brain activation were highly correlated with improved naming of the
      trained pictures, but selectively within the pre-training dysfunctional
      perilesional brain areas. Our results suggest that remodeling of cortical
      functions is possible even years after a stroke. The behavioral gain seems to be
      mediated by brain regions that had been partially deprived from input after the
      initial stroke. We therefore provide first time direct evidence for the
      importance of treatment-induced functional reintegration of perilesional areas in
      a heterogeneous sample of chronic aphasia patients.

PMID- 18096408
TI  - SENSE factors for reliable cortical thickness measurement.
AB  - The purposes of this study were to examine the effect of sensitivity encoding
      (SENSE) factors on cortical thickness measurements and to determine which SENSE
      factor to use to reliably measure cortical thickness in 3.0 T and 1.5 T T1
      weighted MRI images. The 3D T1-TFE images were acquired from 11 healthy
      volunteers with 6 different SENSE acceleration factors from 1.0 (without SENSE
      acceleration) to 4.0 on a 1.5 T scanner, and 9 different SENSE factors from 1.0
      to 6.0, plus a second-day 1.0 acquisition on a 3.0 T scanner. Cortical thickness
      was calculated for the entire cortical surface that was further subdivided into
      33 regions. Repeated measures multivariate analysis of variance revealed that the
      main effect of SENSE factors (F=12.485, df=7, p=0.006) was a significant
      underestimation of cortical thickness at SENSE 5.0 (p=0.022) and 6.0 (p=0.011) at
      3.0 T and at SENSE 4.0 (p<0.000) at 1.5 T. Repeated measures ANOVA showed that
      thickness measurements at the insula, superior temporal sulcus, the medial part
      of the superior frontal lobe, and cingulate cortex are highly affected by SENSE
      factors. SENSE factors affect thickness estimation more significantly at 1.5 T
      and thus 1.5 T imaging provides less reliable estimates using SENSE techniques.
      Faster imaging can be done without too much loss of reliability using a high
      SENSE factor, such as 3.0, at 3.0 T with acquisition time being inversely
      proportional to the SENSE factor.

PMID- 18096409
TI  - Sucrose activates human taste pathways differently from artificial sweetener.
AB  - Animal models suggest that sucrose activates taste afferents differently than non
      caloric sweeteners. Little information exists how artificial sweeteners engage
      central taste pathways in the human brain. We assessed sucrose and sucralose
      taste pleasantness across a concentration gradient in 12 healthy control women
      and applied 10% sucrose and matched sucralose during functional magnet resonance
      imaging. The results indicate that (1) both sucrose and sucralose activate
      functionally connected primary taste pathways; (2) taste pleasantness predicts
      left insula response; (3) sucrose elicits a stronger brain response in the
      anterior insula, frontal operculum, striatum and anterior cingulate, compared to
      sucralose; (4) only sucrose, but not sucralose, stimulation engages dopaminergic
      midbrain areas in relation to the behavioral pleasantness response. Thus, brain
      response distinguishes the caloric from the non-caloric sweetener, although the
      conscious mind could not. This could have important implications on how effective
      artificial sweeteners are in their ability to substitute sugar intake.

PMID- 18096410
TI  - Dorsal stream development in motion and structure-from-motion perception.
AB  - Little is known about the neural development underlying high order visual
      perception. For example, in detection of structures by coherently moving dots,
      motion information must interact with shape-based information to enable object
      recognition. Tasks involving these different motion-based discriminations are
      known to activate distinct specialized brain areas in adults. Here, we
      investigate neural development of normally developing children using functional
      magnetic resonance imaging (fMRI) during perception of randomly moving point
      light dots (RM), coherently moving dots that formed a 3D rotating object (SFM)
      and static dots. Perception of RM enhanced neural activity as compared with
      static dots in motion processing-related visual areas, including visual area 3a
      (V3a), and middle temporal area (hMT+) in 10 adults (age 20-30 years). Children
      (age 5-6 years) showed less pronounced activity in area V3a than adults.
      Perception of SFM induced enhanced neural activity as compared to RM in adults in
      the left parietal shape area (PSA), whereas children increased neural activity
      within dorsal (V3a) and ventral brain areas (lingual gyrus) of the occipital
      cortex. These findings provide evidence of neural development within the dorsal
      pathway. First, maturation was associated with enhanced activity in specialized
      areas within the dorsal pathway during RM perception (V3a) and SFM perception
      (PSA). Secondly, high order visual perception-related neural development was
      associated with a shift in neural activity from low level shape and motion
      specialized areas in children, including partially immature area V3a, to high
      order areas in the parietal lobule (PSA) in adults.

PMID- 18096411
TI  - Correlation between body mass index and striatal dopamine transporter
      availability in healthy volunteers--a SPECT study.
AB  - Recent lines of research suggest that, in addition to hypothalamic sites, the
      striatum dopaminergic system may be a target for regulating homeostasis that may
      be represented by the body mass index (BMI). Although it has been reported that
      the striatal dopamine receptor (DRD2) availability of very obese individuals was
      reduced in proportion to their BMI, the correlation between the striatal dopamine
      system and the BMI in healthy individuals remains unclear. To investigate this
      relationship, the striatal dopamine transporter (DAT) availability of 50 healthy
      volunteers was measured using single position emission computational topography
      (SPECT) and [99mTc]-TRODAT-1. The serum levels of sugar, C-peptide, insulin,
      glycosylated hemoglobin and leptin were measured. Our results showed that age and
      the BMI are significantly negatively associated with the striatal DAT
      availability. Moreover, BMI was the only significant predictor for striatal DAT
      availability. These results suggest that the striatal dopamine system may be
      involved in body mass index regulation. Thus, molecular imaging studies measuring
      the striatal DAT availability should consider the BMI, rather than age, as a
      covariant.

PMID- 18096412
TI  - Development of a robust method for generating 7.0 T multichannel phase images of
      the brain with application to normal volunteers and patients with neurological
      diseases.
AB  - The increased susceptibility effects and high signal-to-noise ratio at 7.0 T
      enable imaging of the brain using the phase of the magnetic resonance signal.
      This study describes and evaluates a robust method for calculating phase images
      from gradient-recalled echo (GRE) scans. The GRE scans were acquired at 7.0 T
      using an eight-channel receive coil at spatial resolutions up to 0.195 x 0.260 x
      2.00 mm. The entire 7.0 T protocol took less than 10 min. Data were acquired from
      forty-seven subjects including clinical patients with multiple sclerosis (MS) or
      brain tumors. The phase images were post-processed using a fully automated phase
      unwrapping algorithm that combined the data from the different channels. The
      technique was used to create the first phase images of MS patients at any field
      strength and the first phase images of brain tumor patients above 1.5 T. The
      clinical images showed novel contrast in MS plaques and depicted microhemorrhages
      and abnormal vasculature in brain tumors with unsurpassed resolution and
      contrast.

PMID- 18096413
TI  - Vagus nerve stimulation improves severely impaired heart rate variability in a
      patient with Lennox-Gastaut-Syndrome.
AB  - Vagus nerve stimulation (VNS) is a new therapeutic option for refractory
      epilepsy. We report a patient with Lennox-Gastaut-Syndrome (LGS) and a severe
      impairment of heart rate variability (HRV), we could demonstrate in our patient
      that HRV was improved by VNS.

PMID- 18096414
TI  - G-protein-coupled receptor Gpr1 and G-protein Gpa2 of cAMP-dependent signaling
      pathway are involved in glucose-induced pexophagy in the yeast Saccharomyces
      cerevisiae.
AB  - In yeast cell, glucose induces various changes of cellular metabolism on genetic
      and metabolic levels. One of such changes is autophagic degradation of
      dispensable peroxisomes (pexophagy) which occurs in vacuoles. We have found that
      in Saccharomyces cerevisiae, defect of G-protein-coupled receptor Gpr1 and G
      protein Gpa2, both the components of cAMP-signaling pathway, strongly suppressed
      glucose-induced degradation of matrix peroxisomal protein thiolase. We conclude
      that proteins Gpr1 and Gpa2 are involved in glucose sensing and signal
      transduction during pexophagy process in yeast.

PMID- 18096415
TI  - Gene expression profiling for improved dissection of acute leukemia: a recently
      identified immature myeloid/T-lymphoid subgroup as an example.
AB  - In this concise overview, we discuss recent findings concerning a distinct
      subgroup of acute myeloid/T-lymphoid leukemia. We describe how we identified
      these leukemias in multiple cohorts of acute myeloid leukemia (AML) using a
      combination of gene expression profiling and additional analytic approaches, and
      how we obtained insight in possible mechanisms leading to their phenotype.

PMID- 18096416
TI  - The molecular heterogeneity of beta-thalassemia in Greece.
AB  - Beta-thalassemia is the most predominant genetic defect in Greece. In this study,
      we investigated the heterogeneity and the frequency of beta-thalassemia mutations
      among 3796 heterozygotes detected in the course of DNA based diagnoses. The
      diagnostic strategy included Denaturing Gradient Gel Electrophoresis (DGGE),
      Allele Specific Oligonucleotide Hybridization (ASO), GAP PCR, Restriction Enzyme
      (RE) analysis and direct sequencing and led to 100% identification of the
      underlying molecular lesion. Six out of 33 different beta-globin defects
      identified accounted for more than 91.4% of the total beta-thalassemia
      chromosomes in Greece. The beta-globin gene mutations cd29 C-->T, IVS-I-2 T-->C,
      IVS-I-5 G-->T, cd37 G-->A and poly A Kurdish AATAAA-->AATAAG are for the first
      time reported in Greece, whereas cd7 GAG-->TAG is a new beta(0)-thalassemia
      mutation detected in an adult man from Albania residing in Greece. Three DNA
      single nucleotide polymorphisms (IVS-I-85 T-->C, IVS-I-91 C-->T and IVS-I-108 T-
      >C) were also revealed; among these, IVS-I-85 T-->C and IVS-I-91 C-->T are new
      and described for the first time worldwide.

PMID- 18096417
TI  - G gamma-196 C-->T, A gamma-201 C-->T: two novel mutations in the promoter region
      of the gamma-globin genes associated with nondeletional hereditary persistence of
      fetal hemoglobin in Greece.
AB  - The increased level of fetal hemoglobin in nondeletional hereditary persistence
      of fetal hemoglobin (nd-HPFH) is associated with several single base
      substitutions in the promoter region of either the (G)gamma- or the (A)gamma
      globin genes. In this study, we report two new forms of nd-HPFH found in two
      unrelated Greek adults with high HbF production (8.6% and 10.2% respectively) and
      positive for the (G)gamma-158 C-->T substitution. Scanning by DGGE analysis and
      direct sequencing of the gamma-globin gene 5' promoter region revealed the
      presence of a (G)gamma-196 C-->T in the first case and an (A)gamma-201 C-->T in
      the second. These mutations seem to reactivate gamma-genes and cause their high
      expression in the adult period.

PMID- 18096418
TI  - Cognitive appraisal and coping in chronic pain patients.
AB  - OBJECTIVES: This study analyses the relationships between patients' cognitive
      appraisals concerning their pain and the coping strategies they use. In addition,
      the way the coping strategy influences the intensity of perceived pain and
      impairment in these patients was studied. METHODS: One hundred and twenty two
      patients with musculoskeletal chronic pain participated. The assessment tools
      were as follows: The Cognitive Appraisal Inventory for Chronic Pain Patients
      (CAI), the Vanderbilt Pain Management Inventory (VPMI), the McGill Pain
      Questionnaire (MPQ) and the Impairment and Functioning Inventory for Chronic Pain
      Patients (IFI). The hypothetical model was empirically tested using the LISREL
      8.20 software package and the unweighted least squares method. RESULTS: High
      levels of challenge appraisal were associated with low levels of passive coping
      and high levels of active coping strategies, whereas the harm, loss or threat
      appraisal predicted high use of passive coping strategies. Passive coping had
      three statistically significant path coefficients: high levels of passive coping
      were associated with low levels of functioning and high levels of pain intensity
      and impairment. However, high levels of active coping reported high levels of
      daily functioning. DISCUSSION: By analysing the cognitive appraisals made by
      chronic pain patients, clinicians could make better predictions regarding the way
      they cope and adjust.

PMID- 18096419
TI  - Molecular docking/dynamics studies of Aurora A kinase inhibitors.
AB  - The binding modes of a known 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole,
      quinazoline, pyrimidine and indolinone series of Aurora A kinase inhibitors have
      been studied using molecular docking and molecular dynamics (MD) simulations.
      Crystallographic bound compound 8 was precisely predicted by our docking
      procedure as evident from 0.43A root mean square (rms) deviations. In addition
      compound 25 (AZ_68) has been successfully cross-docked within the Aurora A kinase
      active site, which was pre-organized for inhibitor 8. We found four key sites (A:
      solvent-exposed front pocket, B: hinge region, C: selectivity pocket and D:
      solvent-exposed phosphate binding region) of the Aurora A kinase contributing
      towards the binding of these compounds. We suggest that the small hydrophobic
      substituents at C-6 position of pyrrolopyrazole nucleus (in compounds 1-8); C-6
      and C-7 positions of the quinazoline moiety (in compounds 9-23); C-2 position of
      the quinazoline and C-4 position of the pyrimidine (in compound 25) could be more
      effective and selective through increased hydrophobic contacts and selectivity
      pocket interactions with these modifications of Aurora A kinase inhibitors. Five
      representative complexes were subjected to 1,000ps of MD simulation to determine
      the stability of the predicted binding conformations. The low value of the root
      mean square deviations (ranging from 0.725 to 1.820A) between the starting
      complex structure and the energy minimized final average complex structure
      suggests that the Glide Extra Precision (XP) derived docked complexes are in a
      state of near equilibrium. The structure-based drug design strategy described in
      this study will be highly useful for the development of new inhibitors with high
      potency and selectivity.

PMID- 18096420
TI  - Binding mode analyses and pharmacophore model development for sulfonamide
      chalcone derivatives, a new class of alpha-glucosidase inhibitors.
AB  - Sulfonamide chalcone derivatives are a new class of non-saccharide compounds that
      effectively inhibit glucosidases which are the major targets in the treatment of
      Type 2 diabetes and HIV infection. Our aim is to explore their binding mode of
      interaction at the active site by comparing with the sugar derivatives and to
      develop a pharmacophore model which would represent the critical features
      responsible for alpha-glucosidase inhibitory activity. The homology modeled
      structure of Saccharomyces cerevisiae alpha-glucosidase was built and used for
      molecular docking of non-sugar/sugar derivatives. The validated docking results
      projected the crucial role of NH group in the binding of sugar/non-sugar
      derivatives to the active site. Ligplot analyses revealed that Tyr71, and Phe177
      form hydrophobic interactions with sugar/non-sugar derivatives by holding the
      terminal glycosidic ring mimics. Molecular dynamic (MD) simulation studies were
      performed for protein alone and with chalcone derivative to prove its binding
      mechanism as shown by docking/Ligplot results. It would also help to substantiate
      the homology modeled structure stability. With the knowledge of the crucial
      interactions between ligand and protein from docking and MD simulation studies,
      features for pharmacophore model development were chosen. The CATALYST/HipHop was
      used to generate a five featured pharmacophore model with a training set of five
      non-sugar derivatives. As validation, all the crucial features of the model were
      perfectly mapped onto the 3D structures of the sugar derivatives as well as the
      newly tested non-sugar derivatives. Thus, it can be useful in virtual screening
      for finding new non-sugar derivatives as alpha-glucosidase inhibitors.

PMID- 18096421
TI  - Isolation and characterization of a neural progenitor cell line from tilapia
      brain.
AB  - Astroglial cell lines have many applications for advancing neural developmental
      and functional studies. However, few astroglial cell lines have been reported
      from fish. In this study, we report the characterization of the immortal cell
      line TB2 isolated from adult tilapia brain tissue. The cell line was established
      at 25 degrees C in L15 medium supplemented with 15% fetal bovine serum. Most of
      the cells displayed a fibrous morphology and were immunoreactive for A2B5
      antigen, glial fibrillary acidic protein (GFAP), keratin, vimentin, and the gap
      junction protein connexin 43 (Cx43). They weakly expressed glutamine synthetase
      (GS), S100 protein, and the neural stem cell markers Sox2 and brain lipid binding
      protein (BLBP). In contrast to astroglia in vivo, most TB2 cells also expressed
      galactocerebroside (GalC), substance P (SP), and tyrosine hydroxylase (TH). By
      immunoblot and RT-PCR, the cells also expressed myelin basic protein (MBP),
      proteolipid protein (PLP), and Cx35. On a poly-L-lysine-coated substrate in
      vitro, TB2 cells showed increases in neuronal dopamine decarboxylase (DDC) and
      microtubule-associated protein 2 (MAP2), indicating that they can initiate
      differentiation into neurons. Taken together, the results suggest that TB2 cells
      are astroglial progenitor cells (neural stem cells) and may develop into
      oligodendrocytes and neurons in a suitable environment. The present study
      advances our knowledge of fish astroglia. However, the factors that affect neural
      development in fish remain unknown, as do the characteristics of the intermediate
      differentiation stages between stem cells and mature nerve cells. The TB2 cell
      line will promote these investigations.

PMID- 18096422
TI  - Involvement of the cytoskeleton in the effect of PGE2 on ion transport in the rat
      distal colon.
AB  - This work aimed at studying the effect of PGE2 on water and chloride absorption
      from the rat distal colon and at investigating the involvement of the
      cytoskeleton in the modulation of colonic transporters. PGE2 increased
      significantly net water and chloride absorption. It increased also the activity
      of the Na+K+-ATPase and the expression of the Na+K+2Cl- cotransporter. The
      increase in pump activity was ascribed to its phosphorylation by PKA or PKC when
      activated upon binding of PGE2 to its receptors, and was deemed responsible for
      the increase in Cl- absorption. Cytochalasin B (CytoB), a disrupter of
      microfilaments, decreased net water and chloride absorption in presence or
      absence of PGE2. Furthermore it down-regulated both pump and cotransporter, and
      lowered Na+K+-ATPase activity. It was suggested that an intact actin cytoskeleton
      is required for the basal and the PGE2-elicited trafficking of both transporters.
      On the other hand, colchicine, an inhibitor of microtubule polymerization, had no
      effect on the absorption of water and chloride but abrogated the stimulatory
      effect of PGE2. Colchicine exerted a similar effect to that of cytochlasin on the
      expression of both pump and cotransporter in presence or absence of PGE2 except
      for the basal activity of the pump which was not altered by microtubule
      disruption. It was concluded that both microfilament and microtubular networks
      are involved in the basal and PGE2-elicited increase in colonic ion absorption.

PMID- 18096423
TI  - Early postnatal ibuprofen and indomethacin effects in suckling and weanling rat
      kidneys.
AB  - The use of indomethacin in preterm newborn infants with symptomatic patent ductus
      arteriosus is associated with compromised renal function. Ibuprofen has been
      shown to be as effective as indomethacin with fewer renal side effects. We
      examined the hypothesis that early postnatal ibuprofen has less adverse effects
      on neonatal rat renal prostanoids, COX-2 expression, and angiotensin II than
      indomethacin. Newborn rats received IP injections of human therapeutic doses of
      ibuprofen or indomethacin on the first 3 days of life. Control rats were treated
      with equivalent volume saline. Kidneys were assessed in suckling and weanling
      rats for prostanoids, COX-2 expression, and angiotensin II. In suckling rats,
      indomethacin suppressed PGE(2) and COX-2 expression, and increased PGF(2alpha),
      whereas ibuprofen increased COX-2 and angiotensin II. Although both NSAIDs
      suppressed 6-ketoPGF(1alpha) and TxB(2) levels in suckling rats, the effect was
      sustained in weanling rats with indomethacin. Our findings demonstrate that
      indomethacin exhibits more potent suppressive effects on renal COX-2 and
      vasodilator prostanoids which are important regulators of renal development and
      function. These long-term, sustained effects may explain in part, why
      indomethacin exerts more severe adverse renal effects than ibuprofen, when
      administered during early postnatal life.

PMID- 18096424
TI  - Transcriptional response of murine macrophages upon infection with opsonized
      Paracoccidioides brasiliensis yeast cells.
AB  - Paracoccidioides brasiliensis is the etiologic agent of the
      Paracoccidioidomycosis the most common systemic mycosis in Latin America. Little
      is known about the regulation of genes involved in the innate immune host
      response to P. brasiliensis. We therefore examined the kinetic profile of gene
      expression of peritoneal macrophage infected with P. brasiliensis. Total RNA from
      macrophages at 6, 24 and 48h was extracted, hybridized onto nylon membranes and
      analyzed. An increase in the transcription of a number of pro-inflammatory
      molecules encoding membrane proteins, metalloproteases, involved in adhesion and
      phagocytosis, are described. We observed also the differential expression of
      genes whose products may cause apoptotic events induced at 24h. In addition,
      considering the simultaneous analyses of differential gene expression for the
      pathogen reported before by our group, at six hours post infection, we propose a
      model at molecular level for the P. brasiliensis-macrophage early interaction. In
      this regard, P. brasiliensis regulates genes specially related to stress and
      macrophages, at the same time point, up-regulate genes related to inflammation
      and phagocytosis, probably as an effort to counteract infection by the fungus.

PMID- 18096425
TI  - Flow analyses in the lower airways: patient-specific model and boundary
      conditions.
AB  - Computational fluid dynamics (CFD) is increasingly applied in the respiratory
      domain. The ability to simulate the flow through a bifurcating tubular system has
      increased the insight into the internal flow dynamics and the particular
      characteristics of respiratory flows such as secondary motions and inertial
      effects. The next step in the evolution is to apply the technique to patient
      specific cases, in order to provide more information about pathological airways.
      This study presents a patient-specific approach where both the geometry and the
      boundary conditions (BC) are based on individual imaging methods using computed
      tomography (CT). The internal flow distribution of a 73-year-old female suffering
      from chronic obstructive pulmonary disease (COPD) is assessed. The validation is
      performed through the comparison of lung ventilation with gamma scintigraphy. The
      results show that in order to obtain agreement within the accuracy limits of the
      gamma scintigraphy scan, both the patient-specific geometry and the BC (driving
      pressure) play a crucial role. A minimal invasive test (CT scan) supplied enough
      information to perform an accurate CFD analysis. In the end it was possible to
      capture the pathological features of the respiratory system using the imaging and
      computational fluid dynamics techniques. This brings the introduction of this new
      technique in the clinical practice one step closer.

PMID- 18096426
TI  - Exposure of mouse oocytes to bisphenol A causes meiotic arrest but not
      aneuploidy.
AB  - Mouse oocytes isolated from large antral follicles were exposed to a wide range
      of concentrations of bisphenol A (BPA) during maturation in vitro (50 ng/ml to 10
      microg/ml BPA in medium). Exposure to high concentrations of BPA (10 microg/ml)
      affected spindle formation, distribution of pericentriolar material and
      chromosome alignment on the spindle (termed congression failure), and caused a
      significant meiotic arrest. However, BPA did not increase hyperploidy at meiosis
      II at any tested concentration. Some but not all meiosis I arrested oocytes had
      MAD2-positive foci at centromeres of chromosomes in bivalents, suggesting that
      they had failed to pass the spindle checkpoint control. In a second set of
      experiments prepubertal mice were exposed sub-chronically for 7 days to low BPA
      by daily oral administration, followed by in vitro maturation of the denuded
      oocytes to metaphase II in the absence of BPA, as this treatment protocol was
      previously reported to induce chromosome congression failure and therefore
      suspected to cause aneuploidy in oocytes. The sub-chronic exposure subtly
      affected spindle morphology and oocyte maturation. However, as with the exposure
      in vitro, there was no evidence that low BPA doses increased hyperploidy at
      meiosis II. In conclusion, the data suggest that mouse oocytes from mice respond
      to BPA-induced disturbances in spindle formation by induction of meiotic arrest.
      This response might result from an effective checkpoint mechanism preventing the
      occurrence of chromosome malsegregation and aneuploidy. Low chronic BPA exposure
      in vivo as such does not appear to pose a risk for induction of errors in
      chromosome segregation at first meiosis in mouse oocytes. Additional factors
      besides BPA may have caused the high rate of congression failure and the
      temporary increase in hyperploidy in mouse metaphase II oocytes reported
      previously.

PMID- 18096428
TI  - Reflections on the impact of advances in the assessment of genetic risks of
      exposure to ionizing radiation on international radiation protection
      recommendations between the mid-1950s and the present.
AB  - Efforts at protecting people against the harmful effects of radiation had their
      beginnings in the early 1900s with the intent of protecting individuals in
      medicine and associated professions. Such efforts remain vital for all of us more
      than 100 years later as part of our 'learning to live with ionizing radiation.'
      The field of radiation protection has evolved slowly over time with advances in
      knowledge on hereditary (i.e., genetic) and carcinogenic effects of radiation
      continually improving our ability to make informed judgments about how best to
      balance risks against benefits of radiation exposure. This paper examines just
      one aspect of these efforts, namely, how advances in knowledge of genetic effects
      of radiation have impacted on the recommendations of the International Commission
      on Radiological Protection (ICRP). The focus is on the period from the mid-1950s
      (when genetic risk estimates were first made) to 2007. This article offers a
      detailed historical analysis and personal perspective, and concludes with a
      synopsis of key developments in radiation protection.

PMID- 18096427
TI  - Spindle formation, chromosome segregation and the spindle checkpoint in mammalian
      oocytes and susceptibility to meiotic error.
AB  - The spindle assembly checkpoint (SAC) monitors attachment to microtubules and
      tension on chromosomes in mitosis and meiosis. It represents a surveillance
      mechanism that halts cells in M-phase in the presence of unattached chromosomes,
      associated with accumulation of checkpoint components, in particular, Mad2, at
      the kinetochores. A complex between the anaphase promoting factor/cylosome
      (APC/C), its accessory protein Cdc20 and proteins of the SAC renders APC/C
      inactive, usually until all chromosomes are properly assembled at the spindle
      equator (chromosome congression) and under tension from spindle fibres. Upon
      release from the SAC the APC/C can target proteins like cyclin B and securin for
      degradation by the proteasome. Securin degradation causes activation of separase
      proteolytic enzyme, and in mitosis cleavage of cohesin proteins at the
      centromeres and arms of sister chromatids. In meiosis I only the cohesin proteins
      at the sister chromatid arms are cleaved. This requires meiosis specific
      components and tight regulation by kinase and phosphatase activities. There is no
      S-phase between meiotic divisions. Second meiosis resembles mitosis. Mammalian
      oocytes arrest constitutively at metaphase II in presence of aligned chromosomes,
      which is due to the activity of the cytostatic factor (CSF). The SAC has been
      identified in spermatogenesis and oogenesis, but gender-differences may
      contribute to sex-specific differential responses to aneugens. The age-related
      reduction in expression of components of the SAC in mammalian oocytes may act
      synergistically with spindle and other cell organelles' dysfunction, and a
      partial loss of cohesion between sister chromatids to predispose oocytes to
      errors in chromosome segregation. This might affect dose-response to aneugens. In
      view of the tendency to have children at advanced maternal ages it appears
      relevant to pursue studies on consequences of ageing on the susceptibility of
      human oocytes to the induction of meiotic error by aneugens and establish models
      to assess risks to human health by environmental exposures.

PMID- 18096429
TI  - Cloning and characterization of Plasmodium vivax serine hydroxymethyltransferase.
AB  - Serine hydroxymethyltransferase (SHMT), which catalyzes the reversible reaction
      of serine and tetrahydrofolate to glycine and methylenetetrahydrofolate, is one
      of the three enzymes in dTMP synthesis pathway that is highly active during cell
      division and has been proposed as a potential chemotherapeutic target in
      infectious diseases and cancer. This is the first study to describe nucleotide
      and amino acid sequences of SHMT from the malaria parasite Plasmodium vivax.
      Sequencing of 12 P. vivax isolates revealed limited polymorphisms in 3 noncoding
      regions. Its biological function is also reported.

PMID- 18096430
TI  - Enhanced severity of virus associated lower respiratory tract disease in asthma
      patients may not be associated with delayed viral clearance and increased viral
      load in the upper respiratory tract.
AB  - BACKGROUND: Viral respiratory infections, particularly human rhinovirus (HRV)
      infections, are the most common cause of asthma exacerbation. HRV infections
      usually lead to more severe and longer duration of lower respiratory tract (LRT)
      symptoms in asthmatics than in otherwise healthy individuals. However, the exact
      mechanism by which viruses contribute to exacerbation of asthma is unknown.
      OBJECTIVES: The main objective of our study was to investigate the relationship
      of the enhanced severity of LRT symptoms to viral dynamics or cytokine responses
      in the upper respiratory tract (URT). STUDY DESIGN: Therefore, we conducted a
      longitudinal study in which asthmatics and healthy controls were followed during
      natural viral respiratory tract infections. RESULTS: Our study confirmed that
      viral respiratory tract infections caused more severe problems of the LRT in
      asthma patients as compared to healthy controls. However, for all subjects, the
      severity of LRT symptoms were not related to viral load or prolonged viral
      shedding in the URT. In addition, we did not detect differences in
      proinflammatory cytokines in the URT between asthmatics and controls. CONCLUSION:
      Persistence of the virus, as well as viral load in the URT, may not be associated
      with the induction and/or persistence of asthmatic symptoms.

PMID- 18096431
TI  - Human CMV vaccine trials: what if CMV caused a rash?
AB  - There are no apparent biologic obstacles to immunization against fetal/placental
      infection with cytomegalovirus (CMV), and vaccine candidates have been developed.
      The major obstacles for a human CMV vaccine are difficulties associated with the
      design and execution of efficacy trials. These trials will be prolonged with
      difficulties in recruiting subjects, and hampered by several factors: First is a
      lack of public awareness of CMV, making recruitment into vaccine trials
      difficult. Second is that trials using fetal infection as an endpoint will be
      prolonged since vaccine administration must occur preconception. Third,
      behavioral changes by subjects will affect infection rates, and controls for
      behavioral changes will have to be in place in any clinical trial. Fourth, not
      all women are at equal risk for CMV infections. High risk women may become
      infected by contact with young children or via sexual activity. Thus, the mode of
      acquisition may be a confounding variable in vaccine efficacy trials. In spite of
      these potential obstacles, successful evaluation of CMV vaccines is possible and
      likely when considered against similar obstacles encountered by several other
      recently licensed vaccines.

PMID- 18096432
TI  - Chronotropic incompetence, beta-blockers, and functional capacity in advanced
      congestive heart failure: time to pace?
AB  - BACKGROUND: Chronotropic incompetence (CI) is often seen in subjects with chronic
      congestive heart failure (CHF). The prevalence of CI, its mechanisms and
      association with beta-blocker use as well as exercise capacity have not been
      clearly defined. METHODS AND RESULTS: Cardiopulmonary exercise tolerance testing
      data for 278 consecutive patients with systolic CHF was analyzed. CI, defined as
      the inability to reach 80% of maximally predicted heart rate was present in 128
      of 278 subjects (46%). The prevalence of CI was highest in those with most
      impaired exercise capacity (72, 48, and 24% for subjects with a VO(2) of <14.0,
      14.0-20.0, and >20.0 ml/kg/min respectively; p=0.001). While subjects with CI had
      lower peak exercise heart rate (114 vs. 152 bpm), and lower peak VO(2) (15.4 vs.
      19.9 ml/kg/min), they were equally likely to be on chronic beta-blocker therapy
      (74% vs. 71%; p=0.51). Heart rate and norepinephrine (NE) levels were measured
      during exercise in a separate cohort of 24 subjects with CHF. There was no
      difference in beta-blocker dose between subjects with and without CI, however,
      exercise induced NE release and Chronotropic Responsiveness Index, a measure of
      post-synaptic beta-receptor sensitivity to NE, were lower in subjects with CI
      (1687+/-911 vs. 2593+/-1451 pg/ml p=0.08; CRI 12.7+/-5.7 vs. 22.1+/-4.7,
      p=0.002). CONCLUSIONS: CI occurs in >70% of subjects with advanced systolic CHF
      irrespective of beta-blocker use and is associated with a trend toward impaired
      NE release, post-synaptic beta-receptor desensitization and reduced exercise
      capacity.

PMID- 18096433
TI  - rAAV-asPLB transfer attenuates abnormal sarcoplasmic reticulum Ca2+ -ATPase
      activity and cardiac dysfunction in rats with myocardial infarction.
AB  - BACKGROUND: Diminished myocardial sarcoplasmic reticulum Ca(2+)-ATPase (SERCA)
      activity and upregulated phospholamban (PLB) level during cardiac dysfunction,
      had been reported in many studies. AIMS: The current study was designed to
      examine the effects of rAAV-antisense phospholamban (asPLB) gene transfer on
      cardiac function, SERCA expression and activity, as well as PLB expression and
      phosphorylation (Pser16-PLB), in a rat myocardial infarction (MI) model. METHODS
      AND RESULTS: Rat MI model was generated by ligating the left anterior descending
      coronary artery. Four weeks later, left ventricular ejection fraction (LVEF),
      left ventricular systolic pressure (LVSP), the maximal rates of increase and
      decrease in intraventricular pressure (+/-dp/dt(max)) were significantly
      depressed, and left ventricular end diastolic pressure (LVEDP) was increased.
      Myocardial PLB was markedly increased while both SERCA activity and Pser16-PLB
      level were decreased. In rAAV-asPLB transfected rats, rAAV-asPLB, which was
      injected into the myocardium around the infarction area immediately after the
      coronary artery ligation, effectively attenuated the depression of cardiac
      function, significantly inhibited the expression of PLB, restored Pser16-PLB
      level and enhanced myocardium SERCA activity. CONCLUSION: rAAV-asPLB transfer in
      rats with MI effectively prevented the progression of heart failure.

PMID- 18096434
TI  - Long-term survival in patients older than 80 years hospitalised for heart
      failure. A 5-year prospective study.
AB  - BACKGROUND: Although heart failure (HF) is frequent in elderly patients, few
      studies have focused on patients older than 80 years. AIMS: To evaluate the
      clinical features, treatment and long-term prognosis of HF in patients older than
      80 years. METHODS AND RESULTS: Consecutive patients hospitalised for a first HF
      episode in the Somme Department (France) during 2000 were prospectively included.
      Of the 799 included patients, 305 (38%) were aged over 80 years. The elderly
      patients were mostly women with a high prevalence of atrial fibrillation,
      ischaemic and hypertensive heart disease. Ejection fraction (EF) was assessed in
      68.5% of elderly patients and 61% had EF >or=50%. Angiotensin-converting enzyme
      inhibitors, beta-blockers, oral anticoagulants and statins were prescribed less
      frequently in elderly patients. The 5-year survival in elderly patients was 19%,
      dramatically lower than the survival of age- and sex-matched general population
      (48%). Cardiovascular causes were recorded in over 60% of deaths. On
      multivariable analysis, cancer, renal insufficiency, old myocardial infarction,
      diabetes, hyponatraemia and age were predictors of mortality in elderly patients.
      Reduced EF was a potent predictor of death (HR 1.72, 95%CI 1.24-2.37, p=0.001) in
      elderly patients. CONCLUSION: Long-term prognosis in HF patients older than 80
      years is poor, with a dramatic excess mortality compared to the elderly general
      population. Life-saving drugs are largely underused in elderly HF patients.

PMID- 18096435
TI  - Beneficial effect of anti-interleukin-4 antibody when administered in a murine
      model of tuberculosis infection.
AB  - There remains much controversy surrounding the role of Th2 cytokines, such as
      interleukin-4 (IL-4), in tuberculosis infection. Here we demonstrate that anti-IL
      4 antibody, administered as a pulse during the early or late stages of murine
      infection, can provide significant reductions in the bacterial burden. The fact
      that substantial benefit can be achieved when treatment is administered during
      established infection strengthens the view that clinical interventions aimed at
      suppressing the IL-4 component of the host immune response seen in tuberculosis
      patients may be beneficial.

PMID- 18096436
TI  - A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid
      mice bearing a targeted mutation in the IL-2 receptor gamma chain gene.
AB  - Immunodeficient NOD-scid mice bearing a targeted mutation in the IL2 receptor
      common gamma chain (Il2rgamma(null)) readily engraft with human stem cells. Here
      we analyzed human peripheral blood mononuclear cells (PBMC) for their ability to
      engraft NOD-scid Il2rgamma(null) mice and established engraftment kinetics,
      optimal cell dose, and the influence of injection route. Even at low PBMC input,
      NOD-scid Il2rgamma(null) mice reproducibly support high human PBMC engraftment
      that plateaus within 3-4 weeks. In contrast to previous stocks of immunodeficient
      mice, we observed low intra- and inter-donor variability of engraftment. NOD-scid
      Il2rgamma(null) mice rendered hyperglycemic by streptozotocin treatment return to
      normoglycemia following transplantation with human islets. Interestingly, these
      human islet grafts are rejected following injection of HLA-mismatched human PBMC
      as evidenced by return to hyperglycemia and loss of human C-peptide. These data
      suggest that humanized NOD-scid Il2rgamma(null) mice may represent an important
      surrogate for investigating in vivo mechanisms of human islet allograft
      rejection.

PMID- 18096437
TI  - New insights into neuromodulatory approaches for the treatment of pain.
AB  - Two lines of evidence about the association between the experience of pain and
      brain state (measured via electroencephalogram or EEG) have recently come to
      light. First, research from a number of sources suggests a link between brain EEG
      activity and the experience of pain. Specifically, this research suggests that
      the subjective experience of pain is associated with relatively lower amplitudes
      of slower wave (delta, theta, and alpha) activity and relatively higher
      amplitudes of faster wave (beta) activity. Second, there has been a recent
      increase in interest in interventions that impact the cortical neuromodulation of
      pain, including behavioral treatments (such as self-hypnosis training and
      neurofeedback) and both invasive and noninvasive brain stimulation. Although a
      direct causal link between experience of pain and brain activity as measured by
      EEG has not been established, the targeting of pain treatment at a cortical level
      by trying to affect EEG rhythms directly is an intriguing possibility.
      PERSPECTIVE: Preliminary evidence suggests the possibility, which has not yet
      adequately tested or proven, that the experience of chronic pain is linked to
      cortical activity as assessed via an electroencephalogram. Support for this
      hypothesis would have important implications for understanding the mechanisms
      that underlie a number of pain treatments, and for developing new innovative
      treatments for chronic pain management.

PMID- 18096438
TI  - Applying centrality of event to persistent pain: a preliminary view.
AB  - Living with persistent pain is a complex experience. Based on clinical
      observations, persistent pain is often described as a stressful life event that
      has significantly altered how patients view themselves and the world around them.
      The Centrality of Event Scale (CES) assesses how much a stressful life event
      serves as a turning point in the individual's life, forms a reference point for
      personal identity, and affects the attribution of meaning to other life
      experiences. In this study, 47 patients with persistent pain were asked to
      complete the CES using "the experience of persistent pain" as the designated
      stressful life event. Data analyses revealed patients scoring high on the CES
      (ie, those who viewed persistent pain as a central life event) were significantly
      more likely to experience higher levels of pain intensity (r = .35, P = .02),
      life interference due to pain (r = .50, P = .002), and psychological distress (r
      = .46, P = .001). Additional analyses revealed that the CES was a significant
      predictor of life interference due to pain and psychological distress even after
      controlling for the effects of age, sex, education, and pain intensity.
      PERSPECTIVE: The experience of persistent pain can serve as a major turning point
      in patients' lives, affect patients' interpretations of other life events, and
      become a key component of patients' identities. The results of this study
      indicate that centrality of event, a relatively new construct, could improve our
      understanding of persistent pain.

PMID- 18096439
TI  - Is the risk of concomitant invasive esophageal cancer in high-grade dysplasia in
      Barrett's esophagus overestimated?
AB  - BACKGROUND & AIMS: Recent studies have claimed long neoplasia-free survival rates
      with endoscopic mucosal resection of high-grade dysplasia (HGD) in Barrett's
      esophagus (BE). However, reports have contended that approximately 40% of
      patients who have esophagectomy for HGD have occult invasive cancer. The aim of
      this study was to use explicit criteria to determine the true prevalence of
      invasive adenocarcinoma in reports of patients who had esophagectomy for HGD in
      BE. METHODS: Studies reporting rates of esophageal cancer in patients who
      underwent esophagectomy for HGD in BE were gathered using MEDLINE and PUBMED. We
      defined invasive esophageal adenocarcinoma (IEAC) as tumor with submucosal
      invasion or beyond. Intramucosal carcinoma (IMC) was not considered IEAC.
      RESULTS: Twenty-three articles were selected for analysis. Most investigators
      reported rates of invasive cancer in the esophagectomy specimen, and the pooled
      average was 39.9% among the 441 patients who underwent an esophagectomy for HGD.
      Reported rates varied from 0% to 73%. A total of 267 patients had American Joint
      Committee on Cancer stage 0 postoperatively, 132 patients had stage I, 23
      patients had stage IIa, 10 patients had stage IIb, and 9 patients had stage III.
      Fourteen studies provided differentiation between intramucosal and submucosal
      invasion. Among 213 patients, only 12.7% had IEAC, whereas 87.3% had HGD or IMC.
      The IEAC rate of 11% among patients with visible lesions is greater than the rate
      of 3% among patients with no visible lesion. CONCLUSIONS: By using strict
      pathologic definitions of invasive disease, the present study indicates the true
      prevalence of IEAC in BE and HGD may have been overestimated significantly.
      Separating IMC from IEAC is clinically relevant because endoscopic techniques
      potentially may treat IMC.

PMID- 18096440
TI  - Mucosal atrophy in celiac disease: extent of involvement, correlation with
      clinical presentation, and response to treatment.
AB  - BACKGROUND & AIMS: Wireless capsule endoscopy provides an opportunity to study
      the macroscopic features in celiac disease by providing a magnified view of the
      intestinal mucosa. In this study, we evaluated the following: (1) the
      distribution of atrophy in untreated celiac disease, (2) the correlation between
      extent of changes and clinical manifestations, (3) the accuracy and interobserver
      agreement of wireless capsule endoscopy assessment, and (4) the effect of gluten
      withdrawal. METHODS: Thirty-eight consecutive patients with untreated biopsy
      proven celiac disease underwent wireless capsule endoscopy. Each subject was
      invited to undergo repeat testing after at least 6 months of gluten withdrawal.
      The video images of each patient were reviewed independently by 2 investigators.
      RESULTS: Thirty-five (92%) subjects had visible atrophy detected by capsule
      endoscopy. Twenty-two (59%) subjects showed an extensive enteropathy, 12 (32%)
      had enteropathy limited to the duodenum, and only 1 had a jejunal enteropathy. No
      association was shown between the extent of the lesion and clinical
      manifestations. Capsule endoscopy had a better overall sensitivity for the
      detection of atrophy as compared with upper endoscopy (92% vs 55%, P = .0005),
      with a specificity of 100%. The overall interobserver agreement for the 2
      reviewers was relatively high (% total agreement, 86.5%). After gluten
      withdrawal, the extent and the pattern of atrophy improved both qualitatively and
      quantitatively. CONCLUSIONS: Celiac disease affects a highly variable portion of
      the small intestine starting at the duodenum. The extent of visible enteropathy
      does not explain differences in clinical presentation. Most subjects with
      visually detected villous atrophy showed a clinically significant improvement
      after gluten withdrawal.

PMID- 18096441
TI  - A prospective, multicenter, population-based study of BRAF mutational analysis
      for Lynch syndrome screening.
AB  - BACKGROUND & AIMS: Mismatch repair (MMR) deficiencies are the hallmark of tumors
      arising in Lynch syndrome, however, in approximately 15% of sporadic colorectal
      cancers (CRC) these deficiencies most often are associated with somatic
      methylation of the MMR gene MLH1. Recently, an oncogenic mutation in the BRAF
      gene has been involved in sporadic CRC showing MMR deficiencies as a result of
      MLH1 promoter methylation. The aim of this study was to evaluate the contribution
      of BRAF V600E mutation analysis in the identification of MSH2/MLH1 gene mutation
      carriers in newly diagnosed CRC patients. METHODS: BRAF V600E mutation was
      analyzed in CRC patients with MMR deficiencies (microsatellite instability and/or
      lack of MLH1/MSH2 protein expression) in the EPICOLON population-based study. The
      effectiveness and efficiency of different strategies were evaluated with respect
      to the presence of MSH2/MLH1 germline mutations. RESULTS: MMR deficiencies were
      detected in 119 of the 1222 CRC patients with tumors showing either
      microsatellite instability (n = 111) or loss of protein expression (n = 81). BRAF
      mutation was detected in 22 (18.5%) of the patients. None of the patients with
      unambiguous germline mutation had BRAF mutation. Regardless of the strategy used
      to identify MSH2/MLH1 gene carriers, the introduction of BRAF analysis in these
      patients slightly improves their effectiveness. The introduction of BRAF mutation
      analysis as a step before germline genetic testing in patients with MMR
      deficiencies achieved a significant reduction in costs per mutation detected.
      CONCLUSIONS: Detection of BRAF V600E mutation could simplify and improve the cost
      effectiveness of genetic testing for hereditary nonpolyposis colorectal cancer,
      especially in patients whose family history is incomplete or unknown.

PMID- 18096442
TI  - Ionotropic glutamate receptor expression in preganglionic neurons of the rat
      inferior salivatory nucleus.
AB  - Glutamate receptor (GluR) subunit composition of inferior salivatory nucleus
      (ISN) neurons was studied by immunohistochemical staining of retrogradely labeled
      neurons. Preganglionic ISN neurons innervating the von Ebner or parotid salivary
      glands were labeled by application of a fluorescent tracer to the lingual
      tonsilar branch of the glossopharyngeal nerve or the otic ganglion respectively.
      We used polyclonal antibodies to glutamate receptor subunits NR1, NR2A, NR2B,
      (NMDA receptor subunits) GluR1, GluR2, GluR3, GluR4 (AMPA receptor subunits), and
      GluR5-7, KA2 (kainate receptor subunits) to determine their expression in ISN
      neurons. The distribution of the NMDA, AMPA and kainate receptor subunits in
      retrogradely labeled ISN neurons innervating the von Ebner and parotid glands was
      qualitatively similar. The percentage of retrogradley labeled ISN neurons
      innervating the parotid gland expressing the GluR subunits was always greater
      than those innervating the von Ebner gland. For both von Ebner and parotid ISN
      neurons, NR2A subunit staining had the highest expression and the lowest
      expression of GluR subunit staining was NR2B for von Ebner ISN neurons and GluR1
      for parotid ISN neurons. The percentage of NR2B and GluR4 expressing ISN neurons
      was significantly different between the two glands. The percentage of ISN neurons
      that expressed GluR receptor subunits ranged widely indicating that the
      distribution of GluR subunit expression differs amongst the ISN neurons. While
      ISN preganglionic neurons express all the GluR subunits, differences in the
      percentage of ISN neurons expression between neurons innervating the von Ebner
      and parotid glands may relate to the different functional roles of these glands.

PMID- 18096443
TI  - Expression of the transcription factor Zfp191 during embryonic development in the
      mouse.
AB  - The human zinc finger protein 191 (ZNF191) is a Kruppel-like protein and can
      specifically interact with the widespread TCAT motif which constitutes the
      HUMTH01 microsatellite in the tyrosine hydroxylase (TH) gene (encoding the rate
      limiting enzyme in the synthesis of catecholamines). Allelic variations of
      HUMTH01 are known to have a quantitative silencing effect on TH gene expression
      and to correlate with quantitative and qualitative changes in the binding by
      ZNF191. This factor has been isolated from bone marrow and promyelocytic leukemia
      cell lines indicating that ZNF191 also plays a role in hematopoiesis. Thus,
      ZNF191 could participate in the regulation of several genes implicated in
      different functions. Moreover, mice that are deficient in Zfp191, the murine
      homologue of ZNF191, have been shown to be severely retarded in development and
      to die approximately at embryonic day 7.5. In order to gain further insight into
      its biological functions, we have analysed the localisation of Zfp191 throughout
      mouse development. Expression was detected early during embryogenesis in
      ectodermal, endodermal, mesodermal and extra-embryonic tissues. In particular,
      Zfp191 was observed in the developing central nervous system. Interestingly, its
      expression levels were prominent in areas of proliferation such as the
      subventricular zone. Zfp191 expression pattern during development can account for
      the phenotypic features of Zfp191(-/-) embryos.

PMID- 18096444
TI  - Genetic diversity of Trypanosoma evansi in beef cattle based on internal
      transcribed spacer region.
AB  - This study was focused on genetic diversity of Trypanosoma evansi which is a
      widely distributed haemoflagellate of veterinary importance that infects a
      variety of larger mammals including horses, mules, camels, buffalo, cattle and
      deer. The genetic diversity of T. evansi of beef cattle LAM19 was accomplished by
      using phylogenetic analysis based on internal transcribed spacer region (ITS).
      Blood sample was collected from a naturally infected beef cattle LAM 19 and
      parasitemia was raised by mouse inoculation. The parasites were collected and
      isolated by using DE 52 DEAE cellulose anion exchange column prior to DNA
      extraction. Upon PCR amplification of ITS region, the product of 1300bp in size
      was obtained. The ITS nucleotide sequences were analyzed and revealed that it
      could demonstrate the genetic diversity of T. evansi of beef cattle LAM19. Based
      on the ITS tree, beef cattle LAM 19 T. evansi were categorized into two main
      groups where the genetic diversity occurred within Group 1. The data could be
      applicable for the survey of parasite dynamics, epidemiological studies as well
      as prevention and control of the disease.

PMID- 18096445
TI  - Hybridization biosensor using 2,9-dimethyl-1,10-phenantroline cobalt as
      electrochemical indicator for detection of hepatitis B virus DNA.
AB  - A label-free biosensor for the detection of oligonucleotides related to hepatitis
      B virus sequence via the interactions of DNA with redox-active complex, 2,9
      dimethyl-1,10-phenantroline cobalt [Co(dmp)(H2O)(NO3)2] is described. The study
      was carried out by the hybridization of 21-mer probe DNA modified on glassy
      carbon electrode (GCE) with target DNA, and [Co(dmp)(H2O)(NO3)2] whose sizes are
      comparable to those of the small groove of native double-helix DNA was used as an
      electrochemical indicator. Electrochemical detection was performed by cyclic
      voltammetry (CV) and differential pulse voltammetry (DPV) over the potential
      range where the [Co(dmp)(H2O)(NO3)2] was active. Under the optimum conditions,
      the electrical signal had a linear relationship with the concentration of target
      DNA ranging from 3.96 x 10(-7) to 1.32 x 10(-6) M, and the detection limit was
      1.94 x 10(-8) M (S/N=3). The biosensor has good selectivity by detecting the
      three-base mismatch sequence ssDNA.

PMID- 18096446
TI  - CPDs and 6-4PPs play different roles in UV-induced cell death in normal and NER
      deficient human cells.
AB  - Ultraviolet (UV) light generates two major DNA lesions: cyclobutane pyrimidine
      dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproducts (6-4PPs), but the
      specific participation of these two lesions in the deleterious effects of UV is a
      longstanding question. In order to discriminate the precise role of unrepaired
      CPDs and 6-4PPs in UV-induced responses triggering cell death, human fibroblasts
      were transduced by recombinant adenoviruses carrying the CPD-photolyase or 6-4PP
      photolyase cDNAs. Both photolyases were able to prevent UV-induced apoptosis in
      cells deficient for nucleotide excision repair (NER) to a similar extent, while
      in NER-proficient cells UV-induced apoptosis was prevented only by CPD
      photolyase, with no effects observed when 6-4PPs were removed by the specific
      photolyase. These results strongly suggest that both CPDs and 6-4PPs contribute
      to UV-induced apoptosis in NER-deficient cells, while in NER-proficient cells,
      CPDs are the only lesions responsible for UV-killing, probably due to the rapid
      repair of 6-4PPs by NER. As a consequence, the difference in skin
      photosensitivity, including carcinogenesis, of most of the xeroderma pigmentosum
      patients and of normal people is probably not only a quantitative aspect, but
      depends on the type of DNA damage induced by sunlight and its rate of repair.

PMID- 18096447
TI  - The Bravo pH capsule system.
AB  - Limitations of existing pH recording methodology have been the impetus for the
      emergence of new technologies focused on improving ambulatory pH monitoring. The
      Bravo pH capsule system (Bravo, Medtronic, Shoreview, MN) is one of the recent
      advances that utilize a wireless system to improve patient compliance and extend
      the period of monitoring. These changes could potentially improve diagnostic
      accuracy along with patient acceptance. Given this fact, the following review
      will evaluate the potential benefits that wireless pH monitoring may have over
      conventional catheter based pH monitoring based on the available data. In
      addition, we will also focus on the technical aspects related to its safety,
      tolerability and diagnostic accuracy.

PMID- 18096448
TI  - Risk factors for hepatitis C virus infection in individuals infected with the
      HIV.
AB  - BACKGROUND: Except for injecting drug use, other routes of transmission for
      hepatitis C virus among HIV-AIDS patients have not been consistently described,
      and risk estimates are often not adjusted for confounding factors. AIMS: To
      evaluate characteristics associated with hepatitis C virus infection in
      individuals infected with the HIV. PATIENTS: Cases were patients co-infected by
      HIV and hepatitis C virus, and controls were infected only by HIV. METHODS: Cases
      and controls were consecutively enrolled at a public health care outpatient HIV
      AIDS reference centre in Porto Alegre, Southern Brazil. RESULTS: A total of 227
      cases (63% men; 40.3+/-8.7 years) and 370 controls (44.6% men; 38.9+/-9.8 years)
      were enrolled in the study. In a multiple logistic regression model, male gender
      (odds ratio 1.9; 95% confidence interval 1.3-2.7), age between 30 and 49 years
      (odds ratio 2.1; 95% confidence interval 1.2-3.7), elementary school education
      (odds ratio 4.2; 95% confidence interval 1.9-9.6), lower family income (odds
      ratio 1.7; 95% confidence interval 1.1-2.7), sharing personal hygiene objects
      (odds ratio 2.0; 95% confidence interval 1.3-3.3), using injected drugs (odds
      ratio 21.6; 95% confidence interval 10.8-43.0) and crack cocaine (odds ratio 2.8;
      95% confidence interval 1.1-6.9) were independently associated with co-infection
      by hepatitis C virus. CONCLUSION: These results confirm the risk profile for
      hepatitis C virus-HIV infection and suggest that sharing personal hygiene objects
      might explain the transmission of virus C to those not infected by the usual
      routes, which may be of relevance for developing preventive strategies.

PMID- 18096449
TI  - Juxtapapillary pancreatic metastasis with obstructive jaundice as isolated
      recurrence of lung adenocarcinoma.

PMID- 18096450
TI  - An unusual case of high alpha-fetoprotein level and liver masses.

PMID- 18096451
TI  - Developmental biology of the human kidney.
AB  - The mammalian kidney consists of highly specialised cells that function in an
      integrated manner to maintain homeostasis of body fluids, electrolytes and
      nutrients. Formation of multicellular structures and differentiation of kidney
      cells are tightly regulated processes that begin during the fifth week and end by
      approximately 34 weeks of human gestation. This review focuses on the
      morphological, cellular and molecular steps required for kidney formation.
      Although some of this information is derived from studies of the human kidney,
      much has arisen from the study of genetic models of mammalian kidney
      morphogenesis. These models reveal mechanisms by which cell lineages are
      established in the embryonic kidney and the genetic pathways that are involved in
      their establishment and maintenance.

PMID- 18096452
TI  - Current controversies in hypothermic neuroprotection.
AB  - In 2005, three randomised controlled trials (RCTs) showed that treating infants
      with hypoxic-ischaemic encephalopathy (HIE) with hypothermia decreased the
      combined outcome of death or disability at 12-18 months, although treatment
      effects were modest. More recently, the US Food and Drug Administration (FDA)
      approved a device for selective head cooling. In addition, the protocol from
      another of the three trials, using equipment available in many hospitals, has
      been in the public domain for over a year. Why has this not led to a consensus
      that hypothermia is the standard of care for HIE? This is explored. Important
      questions for future research will focus on ways to improve on initial results
      with cooling, such as drug plus hypothermia combination therapy and refining
      duration and depth of cooling or duration of rewarming. Although the latter are
      important questions for future clinical trials, those who are convinced by the
      evidence to date should focus on safe implementation of cooling using protocols
      with established safety and efficacy and should consider ways to increase access
      to cooling for eligible babies.

PMID- 18096453
TI  - Dermatofibrosarcoma protuberans in children.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a relatively rare neoplasm affecting
      the skin. It is an infiltrative tumour of intermediate malignancy, with a limited
      potential for metastasis but a high rate of recurrence. The incidence in children
      is even less frequent, although a proportion of those identified in adulthood may
      reflect a delay in diagnosis of childhood DFSP. We report the experience of DFSP
      seen at The Children's Hospital at Westmead (Sydney, Australia). Three children
      aged 5, 10 and 11 years of age underwent surgical excision of their lesions.
      Recurrence was evident in one child whose initial histopathology was not
      definitive for DFSP, and whose initial surgery had not involved wide local
      excision. All three children were male, and all had lesions affecting their
      trunk. One child whose lesion was thought to have been evident since birth may
      have represented congenital DFSP.

PMID- 18096454
TI  - [Nephropathy and autoimmune enteropathies: role of CD4+CD25+FOXP3+ T cell
      regulatory functions].

PMID- 18096455
TI  - [Mycophenolate mofetil restores renal function and spares steroids during
      idiopathic nephrotic syndrome in children. A cohort study].
AB  - Renal function evolution during idiopathic nephrotic syndrome depends on
      treatment toxicity. Cyclosporin is effective as a steroid-sparing agent but
      patients are dependant on this drug, which can lead to renal toxicity.
      Mycophenolate mofetil, a widely used drug in organ transplantation, has short
      term beneficial effects in glomerular diseases, including idiopathic nephrotic
      syndrome. Little is known about mycophenolate mofetil in children and long-term
      evolution. We analysed a cohort of 12 children with steroid-dependant nephrotic
      syndrome due to minimal change disease in remission with cyclosporine therapy.
      They were switched to mycophenolate mofetil, when renal toxicity was diagnosed.
      We evaluated the number of relapses, tolerance of this new treatment, renal
      function and body mass index under mycophenolate. After a follow-up of 31.25
      months, mycophenolate mofetil alone was effective in preventing relapses in eight
      patients, without side effects. Renal function significantly improved and the
      final body mass index decreased. Three patients relapsed on discontinuation of
      mycophenolate mofetil. The results suggest that mycophenolate mofetil is
      effective and safe in preventing relapses in steroid-dependant nephrotic
      syndrome. Furthermore, switching from cyclosporine to mycophenolate mofetil
      restores renal function. Therefore, mycophenolate mofetil might be considered as
      an alternative to cyclosporine, to preserve renal function and spare steroids
      during idiopathic nephrotic syndrome in children.

PMID- 18096457
TI  - Bone mineralization density distribution in health and disease.
AB  - Human cortical and trabecular bones are formed by individual osteons and bone
      packets, respectively, which are produced at different time points during the
      (re)modeling cycle by the coupled activity of bone cells. This leads to a
      heterogeneously mineralized bone material with a characteristic bone
      mineralization density distribution (BMDD) reflecting bone turnover,
      mineralization kinetics and average bone matrix age. In contrast to BMD, which is
      an estimate of the total amount of mineral in a scanned area of whole bone, BMDD
      describes the local mineral content of the bone matrix throughout the sample.
      Moreover, the mineral content of the bone matrix is playing a pivotal role in
      tuning its stiffness, strength and toughness. BMDD of healthy individuals shows a
      remarkably small biological variance suggesting the existence of an evolutionary
      optimum with respect to its biomechanical performance. Hence, any deviations from
      normal BMDD due to either disease and/or treatment might be of significant
      biological and clinical relevance. The development of appropriate methods to
      sensitively measure the BMDD in bone biopsies led to numerous applications of
      BMDD in the evaluation of diagnosis and treatment of bone diseases, while
      advancing the understanding of the bone material, concomitantly. For example,
      transiliacal bone biopsies of postmenopausal osteoporotic women were found to
      have mostly lower mineralization densities than normal, which were partly
      associated by an increase of bone turnover, but also caused by calcium and Vit-D
      deficiency. Antiresorptive therapy causes an increase of degree and homogeneity
      of mineralization within three years of treatment, while normal mineralization
      levels are not exceeded. In contrast, anabolic therapy like PTH decreases the
      degree and homogeneity of matrix mineralization, at least transiently.
      Osteogenesis imperfecta is generally associated with increased matrix
      mineralization contributing to the brittleness of bone in this disease, though
      bone turnover is usually increased suggesting an alteration in the mineralization
      kinetics. Furthermore, BMDD measurements combined with other scanning techniques
      like nanoindentation, Fourier transform infrared spectroscopy and small angle X
      ray scattering can provide important insights into the structure-function
      relation of the bone matrix, and ultimately a better prediction of fracture risk
      in diseases, and after treatment.

PMID- 18096456
TI  - Extracellular calcium regulates parathyroid hormone-related peptide expression in
      osteoblasts and osteoblast progenitor cells.
AB  - Parathyroid hormone-related peptide (PTHrP) has been shown to have anabolic
      effects on bone in women with postmenopausal osteoporosis. On the cellular level
      PTHrP promotes the recruitment of osteogenic cells and prevents apoptotic death
      of osteoblasts and osteocytes. The calcium concentration is considerably higher
      in the vicinity of resorbing osteoclasts than in the plasma. Therefore the
      osteoblasts are likely to be confronted by elevated extracellular calcium
      concentrations in the areas of resorptive activity. The present study was
      designed to assess the possibility that extracellular calcium could regulate
      PTHrP expression in osteoblastic cells. Adult human mesenchymal stem cells (hMSC)
      were cultured and differentiated by standard methods. The PTHrP release into the
      culture media was measured by an immunoradiometric assay and the expression of
      PTHrP, osteocalcin and Runx2 mRNA was assayed by real-time PCR. Increasing the
      extracellular calcium from 1 mM to 5 mM for 24 h resulted in a 4-6-fold increase
      in the PTHrP release. PTHrP mRNA was also increased by elevated calcium levels.
      The effect of calcium stimulation on PTHrP release could be seen within 60 min of
      treatment. The extracellular calcium sensing receptor (CaR) agonist neomycin
      mimicked the effects of calcium and the MEK/MAPK inhibitor PD98059 abolished the
      effect of calcium and neomycin. High extracellular calcium increased the
      mineralization of hMSC and the expression of osteocalcin, but this effect was not
      mimicked by neomycin. Our results show that in hMSC, elevated extracellular
      calcium levels increases both released PTHrP and PTHrP mRNA expression. The
      effect of calcium on PTHrP can be mimicked by activation of the CaR and can be
      diminished by inhibition of the MAPK signalling pathway.

PMID- 18096460
TI  - Molecular imaging of reporter gene expression in prostate cancer: an overview.
AB  - Prostate cancer remains an important and growing health problem. Advances in
      imaging of prostate cancer may help to achieve earlier and more accurate
      diagnosis and treatment. We review the various strategies using reporter genes
      for molecular imaging of prostate cancer. These approaches are emerging as
      valuable tools for monitoring gene expression in laboratory animals and humans.
      Further development of more sensitive and selective reporters, combined with
      improvements in detection technology, will consolidate the position of reporter
      gene imaging as a versatile method for understanding of intracellular biological
      processes and the underlying molecular basis of prostate cancer, as well as
      potentially establishing a future role in the clinical management of patients
      afflicted with this disease.

PMID- 18096461
TI  - Radiopharmaceuticals for renal positron emission tomography imaging.
AB  - Radiopharmaceuticals for functional renal imaging, including renal blood flow,
      renal blood volume, glomerular excretion, and metabolism have been available for
      some time. This review outlines radiopharmaceuticals for functional renal imaging
      as well as those that target pertinent molecular constituents of renal injury and
      repair. The angiotensin and endothelin receptors are particularly appealing
      molecular targets for renal imaging because of their association with renal
      physiology and pathology. Other targets such as the vascular endothelial growth
      factor (VEGF) receptor, integrin, or phosphatidylserine have been investigated at
      length for cancer imaging, but they are just as important constituents of the
      renal injury/repair process. Various diseases can involve identical mechanisms,
      such as angiogenesis and apoptosis, and radiopharmaceuticals developed for these
      processes in other organs can also be used for renal imaging. The sensitivity and
      spatial resolution of positron emission tomography makes it an ideal tool for
      molecular and functional kidney imaging. Radiopharmaceutical development for the
      kidneys must focus on achieving high target selectivity and binding affinity,
      stability and slow metabolism in vivo, and minimal nonspecific accumulation and
      urinary excretion.

PMID- 18096462
TI  - Monitoring renal function and limitations of renal function tests.
AB  - Chronic kidney disease (CKD) is a world-wide public health problem, with adverse
      outcomes of kidney failure, cardiovascular disease, and premature death. The
      National Kidney Foundation, through its Kidney Disease Quality Outcome Initiative
      (K/DOQI) and other National institutions, recommend glomerular filtration rate
      (GFR) estimates for the definition, classification, screening, and monitoring of
      CKD. Prediction equations based on serum creatinine values were chosen both for
      adults (Cockcroft-Gault [C-G] and Modification of Diet in Renal Disease [MDRD]
      study equations) and for children (Schwartz and Counahan-Barratt equations). This
      review aims to evaluate from recent literature the clinical efficiency and
      relevance of these equations in terms of bias, precision, and reproducibility in
      different specific indications (eg, screening CKD, assessment of disease
      progression, or therapy efficacy) in different populations. Because these
      prediction equations based on serum creatinine have limitations, especially in
      the normal or near-normal GFR range, kidney transplant recipients, and pediatric
      populations, other prediction equations based on serum cystatin C value were also
      considered as possibly more sensitive GFR surrogate markers. Recent guidelines
      state that the cystatin C-based prediction equation cannot be recommended for use
      in clinical practice. With prediction equations based on serum creatinine, the
      National Kidney Disease Education Program (NKDEP) recommendations are to report a
      numerical estimate in round numbers only for GFR values <60 mL/min per 1.73 m(2).
      The MDRD equation generally outperforms the C-G equation but may still have a
      high level of bias, depending on creatinine assay calibration, and low precision
      with, at best, approximately 80% of estimated GFR in the "accuracy range" of 70
      130% of the measured GFR value, even in patients with known CKD. According to
      Kidney Disease Improving Global Outcomes (KDIGO) recommendations, many
      indications remain for GFR measurements using a clearance method. In that
      context, it should be recalled that radiolabeled-tracer plasma or urinary
      clearance methods, are safe, simple, accurate and reproducible.

PMID- 18096463
TI  - Measurement of glomerular filtration rate with magnetic resonance imaging:
      principles, limitations, and expectations.
AB  - Glomerular filtration rate (GFR) is the most useful quantitative index of renal
      function and is used clinically as the gold standard of renal dysfunction. Follow
      up of patients with impaired renal function requires reliable measurements of
      GFR. Thus, serial GFR values estimated from magnetic resonance imaging (MRI)
      would be worthwhile if easy to obtain, accurate, and reproducible. Nuclear
      medicine-based techniques remain at present the reference method for
      quantification of GFR, but MRI should be able to compete in the near future.
      Several methods are available for measurement of GFR using MRI and freely
      filtered Gd-chelates: (1) measurement of the clearance of the agent using blood
      samplings; (2) measurement of the plasma clearance of the agent using signal
      intensity changes within abdominal organs; (3) measurement of the extraction
      fraction of the agent; and (4) monitoring of tracer intrarenal kinetics. A high
      heterogeneity of protocols (e.g., in acquisition mode, dose of contrast,
      postprocessing techniques) is noted in the literature, reflecting the number of
      technical challenges that will have to be solved before to reach a consensus, and
      the reported accuracy and reproducibility are insufficient for justifying their
      use in clinical practice now.

PMID- 18096464
TI  - Imaging in urinary tract infections: current strategies and new trends.
AB  - The aim of imaging in a child with urinary tract infection (UTI) is to detect
      abnormalities that require appropriate treatment or findings that can be acted on
      to prevent development of complications (hypertension, chronic renal failure or
      pregnancy-related complications). Imaging protocols in pediatric urinary tract
      infections are evolving. From strategies based on extensive investigations in all
      children younger than 7 years of age, we are slowly moving to imaging strategies
      focused on children at risk of developing renal damage and possibly long-term
      complications. The article provides an overview on urinary tract infections,
      their complications and the use of imaging in their management. The different
      imaging strategies in children with UTIs (including the recommendation of
      excluding from imaging certain groups of patients) still needs full evaluation.
      It is interesting to note, however, a slow move from wide use of cystography in
      all children with UTI, which has been standard practice for many years but was
      probably not based on solid scientific evidence, toward a more focused use of
      cystograms in specific groups of children.

PMID- 18096465
TI  - Decision support systems in diuresis renography.
AB  - The volume of diagnostic imaging studies performed in the United States is
      rapidly increasing resulting from an increase in the number of patients as well
      as an increase in the volume of studies per patient. Concurrently, the number and
      complexity of images in each patient data set are also increasing. Nuclear
      medicine physicians and radiologists are required to master an ever-expanding
      knowledge base whereas the hours available to master this knowledge base and
      apply it to specific tasks are steadily shrinking. The convergence of an
      expanding knowledge base and escalating time constraints increases the likelihood
      of physician errors. The problem is particularly acute for low-volume studies
      such as MAG3 diuresis renography where many imagers may have had limited training
      or experience. To address this problem, renal decision support systems (DSS) are
      being developed to assist physicians evaluate suspected obstruction in patients
      referred for diuresis renography. Categories of DSS include neural networks, case
      based reasoning, expert systems and statistical systems; RENEX and CART are
      examples of renal DSS currently in development. RENEX (renal expert) uses a set
      of rules obtained from human experts to analyze a knowledge base of expanded
      quantitative parameters obtained from diuresis MAG3 scintigraphy whereas CART
      (classification and regression tree analysis) is a statistical method that grows
      and prunes a decision tree based on an analysis of these quantitative parameters
      in a training data set. RENEX can be queried to provide the reasons for its
      conclusions. Initial data show that the interpretations provided by RENEX and
      CART are comparable to the interpretations of a panel of experts blinded to
      clinical information. This project should serve as a benchmark for the scientific
      comparison and collaboration of these 2 fields of medical decision-making.
      Moreover, we anticipate that these DSS will better define the essential
      interpretative criteria, foster standardized interpretation, teach trainees to
      better interpret renal scans, enhance diagnostic accuracy and provide a
      methodology applicable to other diagnostic problems in radiology and medicine.

PMID- 18096466
TI  - International Scientific Committee of Radionuclides in Nephrourology (ISCORN)
      consensus on renal transit time measurements.
AB  - This report is the conclusion of the international consensus committee on renal
      transit time (subcommittee of the International Scientific Committee of
      Radionuclides in Nephrourology) and provides recommendations on measurement,
      normal values, and analysis of clinical utility. Transit time is the time that a
      tracer remains within the kidney or within a part of the kidney (eg, parenchymal
      transit time). It can be obtained from a dynamic renogram and a vascular input
      acquired in standardized conditions by a deconvolution process. Alternatively to
      transit time measurement, simpler indices were proposed, such as time of maximum,
      normalized residual activity or renal output efficiency. Transit time has been
      mainly used in urinary obstruction, renal artery stenosis, or renovascular
      hypertension and renal transplant. Despite a large amount of published data on
      obstruction, only the value of normal transit is established. The value of
      delayed transit remains controversial, probably due to lack of a gold standard
      for obstruction. Transit time measurements are useful to diagnose renovascular
      hypertension, as are some of the simpler indices. The committee recommends
      further collaborative trials.

PMID- 18096467
TI  - Immune-mediated thrombocytopenias: focus on chronic immune thrombocytopenic
      purpura.

PMID- 18096468
TI  - Current options for the treatment of idiopathic thrombocytopenic purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized
      by low platelets and bleeding. Platelet autoantibodies result in accelerated
      platelet destruction by the reticuloendothelial cells in the spleen and liver,
      overwhelming the compensatory capability of the bone marrow to increase platelet
      production. The goal of treatment for patients with ITP is to raise the platelet
      count to high enough levels to prevent bleeding using the least toxic therapy,
      recognizing the generally benign nature of the illness. Corticosteroids,
      intravenous immune globulin, and splenectomy remain mainstays of treatment;
      however, newer therapies including rituximab and the thrombopoietin receptor
      agonists are remodeling conventional treatment algorithms. Immune suppressant
      medications and cytotoxic drugs continue to be used in patients with severe and
      chronic refractory ITP with some success; however, estimates of the effect of
      these and other treatments are limited by the lack of randomized trials using
      clinical end points. In this article, treatments for ITP are reviewed with a
      focus on their mechanism of action and the best available evidence from clinical
      studies. A move towards early aggressive therapy may alter the natural history of
      this self-perpetuating illness.

PMID- 18096469
TI  - Other immune thrombocytopenias.
AB  - Immune thrombocytopenic purpura (ITP) can be classified as primary (known also as
      idiopathic thrombocytopenic purpura) or as secondary to an underlying condition
      such as a malignant or nonmalignant disorder. Commonly occurring conditions
      associated with secondary ITP include lymphoproliferative disorders (chronic
      lymphocytic leukemia [CLL], Hodgkin's disease and non-Hodgkin's lymphomas),
      autoimmune collagen vascular diseases (systemic lupus erythematosus [SLE],
      thyroid disease, antiphospholipid syndrome [APS]), and chronic infections (human
      immunodeficiency virus [HIV], Helicobacter pylori, hepatitis C virus [HCV]). The
      mechanism of platelet destruction in thrombocytopenias associated with
      lymphoproliferative disorders and collagen vascular diseases is identical to the
      autoimmune mechanism seen in primary ITP. Drug-induced thrombocytopenias are
      uncommon and generally resolve quickly upon drug discontinuation, but are often
      attributed to other causes. Platelet destruction in infection-associated ITP
      occurs via various mechanisms including accelerated platelet clearance due to
      immune complex disease as seen in HIV infection or cross-reactivity of anti
      platelet glycoprotein antibodies and viral antigens in HIV, HCV, and H pylori
      infections (antigenic mimicry). In patients with HCV-related cirrhotic liver
      disease, splenic sequestration secondary to portal hypertension and decreased
      production of thrombopoietin may further contribute to development of
      thrombocytopenia. The current treatment paradigm for secondary ITP varies
      according to the underlying condition. Standard treatments for primary ITP
      (corticosteroids, IVIG, anti-D, splenectomy) are often successful in secondary
      ITP. In cases of ITP with H pylori and HCV infection, treatment should focus on
      the underlying disorder.

PMID- 18096470
TI  - The pathogenesis of chronic immune thrombocytopenic purpura.
AB  - Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which
      the patient's immune system reacts with a platelet autoantigen(s) resulting in
      thrombocytopenia due to immune-mediated platelet destruction and/or suppression
      of platelet production. Platelet membrane proteins, for reasons that are unclear,
      become antigenic and stimulate the immune system to produce autoantibodies and
      cytotoxic T cells. The initial antigenic response probably occurs in the spleen
      followed by stimulation of other antibody-producing tissues, particularly the
      bone marrow. Autoantibodies against platelet glycoprotein (GP) IIb-IIIa and/or
      GPIb-IX are produced by the majority of ITP patients and can be detected using
      antigen-specific assays. Many patients produce multiple antibodies; this has been
      attributed to the phenomenon of epitope spreading. Once produced, autoantibody
      may either bind to platelets, causing their destruction by either phagocytosis or
      possibly complement activation and lysis, or bind to megakaryocytes, resulting in
      decreased thrombopoiesis. Evidence for platelet destruction in ITP includes the
      following: (1) infusion of ITP blood or plasma into normal recipients may result
      in thrombocytopenia; (2) there is decreased intravascular survival of
      radiolabeled platelets in most ITP patients; (3) morphologic and in vitro
      evidence of platelet phagocytosis can be demonstrated; and (4) cytotoxic T cells
      can induce lysis of autologous platelets. Evidence for suppressed platelet
      production in ITP includes the following: (1) morphologic studies show
      megakaryocyte damage in most ITP patients; (2) there is normal or decreased
      platelet turnover in the majority of patients; (3) in vitro studies show antibody
      induced inhibition of megakaryocyte production and maturation; and (4) an
      increase in the platelet count occurs in many ITP patients receiving treatment
      with thrombopoietin mimetics. In summary, activation of the immune system by
      platelet autoantigens in ITP may result in platelet destruction and/or inhibition
      of platelet production. The importance of each mechanism in the individual
      patient probably varies.

PMID- 18096471
TI  - Thrombopoietin mimetic agents in the management of immune thrombocytopenic
      purpura.
AB  - Thrombopoietin (TPO) is a potent endogenous cytokine and the principal regulator
      of platelet production. Advances in the understanding of the structure of TPO
      enabled development of the first generation of thrombopoietic growth factors,
      recombinant human thrombopoietin (rhTPO) and pegylated human recombinant
      megakaryocyte growth and development factor (PEG-rHuMGDF). Clinical results
      showed that these agents were effective in promoting increases in platelet counts
      in a variety of thrombocytopenic disorders. However, clinical development was
      halted when studies demonstrated risk for autoantibody formation with cross
      reactivity to endogenous TPO. A second generation of thrombopoietic growth
      factors, including TPO peptide and nonpeptide mimetics and TPO agonist
      antibodies, utilizing different mechanisms from recombinant growth factors to
      promote platelet production, are currently in development. The TPO peptide
      mimetic AMG 531 and the nonpeptide mimetic eltrombopag are in advanced clinical
      trials and have both resulted in dose-dependent increases in platelets in healthy
      subjects and in significant increases in platelets in patients with chronic
      immune thrombocytopenic purpura (ITP). Clinical trials are also being conducted
      to examine the efficacy and safety of eltrombopag to treat thrombocytopenia in
      hepatitis C virus (HCV)-infected individuals. These agents appear to be well
      tolerated and the formation of autoantibodies appears to be limited to first
      generation growth factors. Increases in marrow reticulin have been demonstrated
      with some growth factors, but this appears to be a reversible phenomenon and is
      not associated with formation of collagen fibrosis. There appears to be no
      increased incidence of thrombotic events in patients who achieve high platelet
      counts with growth factor treatments, and although occasional thrombotic events
      have been reported, their association to the treatment is uncertain. While there
      is evidence that activation of signaling pathways involved in platelet production
      may result in reduction in the threshold for platelet activation, this appears to
      have minimal clinical relevance for the use of thrombopoietin growth factors.

PMID- 18096472
TI  - Registry of the International Society for Heart and Lung Transplantation: tenth
      official pediatric lung and heart/lung transplantation report--2007.
AB  - This tenth official pediatric report of the International Society for Heart and
      Lung Transplantation (ISHLT) covers the international pediatric lung and heart
      lung transplantation experience from 1982 to 2006. As of last year's report,
      pediatric lung and heart-lung transplant data are now reported separately from
      pediatric heart transplant data and adult lung transplant data. For the first
      time this year, Registry data are analyzed by geographic region in addition to
      the usual aggregate analyses. All figures and tables included in this report and
      additional supplementary slides are available from the ISHLT website
      (www.ishlt.org/registries).

PMID- 18096473
TI  - Revision of the 1996 working formulation for the standardization of nomenclature
      in the diagnosis of lung rejection.
AB  - In 1990, an international grading scheme for the grading of pulmonary allograft
      rejection was adopted by the International Society for Heart and Lung
      Transplantation (ISHLT) and was modified in 1995 by an expanded group of
      pathologists. The original and revised classifications have served the lung
      transplant community well, facilitating communication between transplant centers
      with regard to both patient management and research. In 2006, under the direction
      of the ISHLT, a multi-disciplinary review of the biopsy grading system was
      undertaken to update the scheme, address inconsistencies of use, and consider the
      current knowledge of antibody-mediated rejection in the lung. This article
      summarizes the revised consensus classification of lung allograft rejection. In
      brief, acute rejection is based on perivascular and interstitial mononuclear
      infiltrates, Grade A0 (none), Grade A1 (minimal), Grade A2 (mild), Grade A3
      (moderate) and Grade A4 (severe), as previously. The revised (R) categories of
      small airways inflammation, lymphocytic bronchiolitis, are as follows: Grade B0
      (none), Grade B1R (low grade, 1996, B1 and B2), Grade B2R (high grade, 1996, B3
      and B4) and BX (ungradeable). Chronic rejection, obliterative bronchiolitis
      (Grade C), is described as present (C1) or absent (C0), without reference to
      presence of inflammatory activity. Chronic vascular rejection is unchanged as
      Grade D. Recommendations are made for the evaluation of antibody-mediated
      rejection, recognizing that this is a controversial entity in the lung, less well
      developed and understood than in other solid-organ grafts, and with no consensus
      reached on diagnostic features. Differential diagnoses of acute rejection, airway
      inflammation and chronic rejection are described and technical considerations
      revisited. This consensus revision of the working formulation was approved by the
      ISHLT board of directors in April 2007.

PMID- 18096474
TI  - Influence of different implantation techniques on long-term survival after
      orthotopic heart transplantation: an echocardiographic study.
AB  - BACKGROUND: Orthotopic heart transplantation (OHT) was initially done by the
      biatrial technique, although the bicaval technique has recently become more
      popular. The aim of this study was to compare OHT outcomes when using the bicaval
      technique vs the biatrial technique. METHODS: A total of 615 patients were
      transplanted at the Cleveland Clinic Foundation from January 1993 and October
      2003 (biatrial technique: n = 293; bicaval technique: n = 322). The average
      follow-up period was 4.2 +/- 2.9 years (range 1 to 11 years). Patients who were
      supported with a left ventricular assist device (prior to transplant) and who
      could not be weaned off respiratory support were excluded. RESULTS: Patients in
      both groups were similar with regard to pre-operative characteristics. The peri
      operative mortality showed no statistical significant differences between the two
      groups. The left atrium was significantly more enlarged in the biatrial group.
      The bicaval group showed a significantly reduced incidence of tricuspid
      regurgitation. Survival at 10-year follow-up was 87.3% in the bicaval group and
      79.9% in the biatrial group (p < 0.05). Left ventricular ejection fraction
      (LVEF), right ventricular ejection fraction (RVEF) and moderate to severe
      tricuspid regurgitation were significant risk factors for death in both groups.
      The bicaval technique showed a significantly better mortality outcome.
      CONCLUSIONS: This study showed that the bicaval technique for OHT offers a better
      outcome than the biatrial technique. The significant reduction of left atrial
      size and atrioventricular valve regurgitation in the bicaval group may have a
      major impact on the long-term preservation of cardiac function and survival.

PMID- 18096475
TI  - Short-course total lymphoid irradiation for refractory cardiac transplantation
      rejection.
AB  - BACKGROUND: Total lymphoid irradiation (TLI) has been used as an effective
      therapy for refractory allograft cardiac transplantation rejection. In this study
      we assessed our short-course TLI regimen for treatment of this condition.
      METHODS: A short course of TLI (4.5 Gy in 4 fractions) was given to 6 patients
      with recalcitrant allograft cardiac transplant rejection at the Royal Perth
      Hospital. RESULTS: Treatment compliance was excellent with most patients having
      no acute toxicity. With a median follow-up of 25 months, 83% of patients remain
      alive and disease-free. CONCLUSIONS: To date, no convincing evidence of radiation
      related late effects have been documented with TLI. Nonetheless, larger scale
      trials are required for validation before this approach can be widely
      incorporated into the current transplantation (Tx) rejection regimen.

PMID- 18096476
TI  - Transcriptional signals of T-cell and corticosteroid-sensitive genes are
      associated with future acute cellular rejection in cardiac allografts.
AB  - BACKGROUND: Profiling mRNA levels of 11 informative genes expressed by
      circulating immune effector cells identifies cardiac allograft recipients at low
      risk for current moderate-severe acute cellular rejection (ACR). METHODS: We
      conducted a nested case-control study of 104 cardiac allograft recipients to
      investigate the association of transcriptional profiles of blood samples with
      either a future rejection episode within 12 weeks of a baseline clinical sample
      or persistent histologic quiescence for the same time period. RESULTS: The
      transcription profile yielded a score (0 to 40 scale) of 27.4 +/- 6.3 for future
      rejectors (n = 39) and 23.9 +/- 7.1 for controls (n = 65) (p = 0.01). In patients
      who were <or=180 days post-transplant, the gene expression score was 28.4 +/- 4.9
      for rejectors (n = 28) and 22.4 +/- 7.5 for controls (n = 48) (p < 0.001). In
      this period, no samples from patients who went on to reject within 12 weeks had
      gene expression scores of <20. Differential expression of the gene IL1R2 was
      significantly associated with future events. Of 33 additional genes profiled, 5
      supported corticosteroid-sensitive constituents (IL1R2 and FLT3), whereas 6
      supported T-cell activation (PDCD1). CONCLUSIONS: These data suggest that
      pathways regulating T-cell homeostasis and corticosteroid sensitivity are
      associated with future ACR in cardiac allografts and suggest that these signals
      are evident before histologically detectable rejection.

PMID- 18096477
TI  - Early screening for antibody-mediated rejection in heart transplant recipients.
AB  - BACKGROUND: The International Society for Heart and Lung Transplantation (ISHLT)
      recently established a diagnostic scheme for antibody-mediated rejection (AMR).
      Currently, however, confirmatory immunohistochemistry studies are recommended
      only if AMR is clinically or histologically suspected. In this study, we examine
      whether a pattern of repetitive AMR occurred early enough after transplantation
      to warrant prospective immunohistochemistry screening in all recently
      transplanted recipients. METHODS: We queried our pathology database of adult and
      pediatric endomyocardial biopsies (EMBs) from 1985 to 2005. All EMB specimens
      were prospectively studied by immunofluorescence in the early post-operative
      period. AMR was defined as the presence of complement and immunoglobulin deposits
      on frozen section. Only patients classified as antibody-mediated rejectors (>or=3
      episodes of AMR) were included. Cumulative incidence and time from transplant to
      first and third AMR episodes were obtained. RESULTS: Three hundred seventy-five
      of 870 heart transplant recipients had >or=3 episodes of AMR. Mean age of
      recipients was 45.6 years and 78% were male. A total of 19,569 EMBs comprised the
      study data. By 100 days post-transplant, 85% of patients had their first and 54%
      their third AMR. In addition, patients showed a clear trend of early clustering
      of AMR-positive biopsies. Results were similar regardless of whether or not
      muromonab-CD3 (Orthoclone OKT3) induction was used. CONCLUSIONS: We advocate
      early immunohistochemical surveillance testing for AMR to supplement the
      diagnostic algorithm established by the ISHLT, because a pattern of AMR becomes
      manifest soon after transplantation. This change will allow earlier detection of
      asymptomatic AMR and may prompt changes in immunosuppression strategies to avoid
      adverse outcomes.

PMID- 18096478
TI  - Gene expression profiling distinguishes a molecular signature for grade 1B mild
      acute cellular rejection in cardiac allograft recipients.
AB  - BACKGROUND: Gene expression profiling distinguishes the absence or presence of
      moderate to severe grades of acute cellular rejection in cardiac allograft
      recipients using a 20-gene classifier. We explored the hypothesis that the
      rejection classifier also differentiates various forms of mild rejection and we
      performed sub-analyses based on time post-transplant and confirmatory pathology
      interpretations. METHODS: A post hoc analysis of 265 CARGO study patients and 714
      clinical encounters focused on the correlation of rejection classifier-derived
      gene expression (GE) scores for blood samples accompanying endomyocardial
      biopsies. Biopsy grades assigned by a study center pathologist (center) were re
      interpreted by three pathologists (panel) in a blinded manner. RESULTS: Mean GE
      scores not only differentiated Grades >or=3A from Grade 0 (p < 0.00001, center or
      panel), but also from Grades 1A or 2 (p < 0.05, center or panel), based on mild
      rejection sub-groups defined by the ISHLT 1990 grading system. In contrast, mean
      GE scores for Grades 1B and >or=3A were indistinguishable, using either center or
      panel interpretation. Sub-group analyses of encounters from 2 to 6 months or >6
      months post-transplant showed similar results for the classifier's ability to
      discriminate moderate to severe rejection from Grades 1A and 2 mild rejection,
      but indistinguishable mean GE scores for Grades >or=3A and the Grade 1B sub
      group. Of the classifier's 11 informative genes, expression of MIR and WDR40
      showed statistically significant increases for both Grade 1B and Grade >or=3A
      rejection, while expression of PDCD1 or SEMA7A showed similar directional
      patterns without achieving statistical significance. CONCLUSIONS: These data
      demonstrate that GE scores discriminate moderate to severe rejection from Grades
      1A and 2 mild rejection. However, a sub-group of mild rejection cases, defined as
      Grade 1B according to the 1990 grading system, share a molecular signature more
      consistent with moderate to severe rejection. The clinical relevance of these
      data remains to be defined.

PMID- 18096480
TI  - A single-center experience with ganciclovir-resistant cytomegalovirus in lung
      transplant recipients: treatment and outcome.
AB  - BACKGROUND: Cytomegalovirus (CMV) disease is a major cause of morbidity and
      mortality after lung transplantation despite ganciclovir prophylaxis. The
      emergence of ganciclovir-resistant CMV in lung transplant patients has been
      reported, although the optimal strategy for the management of these infections
      remains uncertain. A review of the results of glanciclovir susceptibility testing
      in lung transplant recipients was performed. METHODS: We found 54% (113 of 210)
      of lung transplant patients developed CMV infection over a 4-year study period
      with ganciclovir-resistant CMV infection occurring in >5% of patients (6 of 113).
      The demographic and clinical characteristics of patients who developed
      ganciclovir-resistant vs -sensitive CMV infection were similar, although 50% (3
      of 6) patients who developed resistance were CMV mismatched (D(+)/R(-) serology).
      All patients' CMV isolates had mutations in the UL97 gene. In addition, the 3
      mismatch patients also had CMV with mutations in the UL54 gene. RESULTS:
      Treatment with a combination of foscarnet and ganciclovir or foscarnet alone for
      ganciclovir-resistant infection led to a significant reduction in virologic load
      in all patients (p = 0.03), although transient increases in viremia were observed
      in some patients early after treatment. Renal function worsened after treatment,
      but overall it was not significantly different from pre-treatment values (p =
      0.07). CONCLUSIONS: Single or combination therapy with foscarnet is effective for
      treatment of ganciclovir-resistant isolates and excessive concern regarding
      toxicity should not preclude consideration of these treatments when clinically
      indicated.

PMID- 18096479
TI  - Recombinant adenoviral gene transfer does not affect cardiac allograft
      vasculopathy.
AB  - BACKGROUND: Adenovirus serotype 5 has remained the pre-eminent vector in pre
      clinical gene therapy applications in cardiac transplantation. Concerns over the
      potential effects of adenoviral vectors on the later development of cardiac
      allograft vasculopathy (CAV) are addressed in this study. METHODS: Hearts (n =
      22) harvested from Brown Norway rats were perfused ex vivo with either University
      of Wisconsin (UW) solution with no virus, Ad-CMV-LacZ or Ad-CMV-Null. Donor
      hearts were transplanted heterotopically into the abdomen of Lewis rats. All
      recipients received cyclosporine for the duration of the experiment. Transplanted
      hearts were recovered for analysis at 120 days. Sections of the heart were
      stained with elastic-van Gieson stain for morphometric analysis of the vessels to
      ascertain the degree of vascular luminal occlusion. Hematoxylin-eosin staining
      facilitated diagnosis of chronic rejection. RESULTS: Seventy-seven percent of
      transplanted hearts showed signs of chronic rejection with no difference in the
      proportion of animals between groups (p = 0.797). No difference was noted in the
      degree of vascular luminal occlusion between the Ad-Null (0.57 +/- 0.22), Ad-LacZ
      (0.62 +/- 0.19) and UW (0.47 +/- 0.29) groups (p = 0.653). CONCLUSIONS:
      Vascularized cardiac allografts transplanted from Brown Norway to Lewis rats
      demonstrated cardiac allograft vasculopathy CAV at 120 days. Adenoviral perfusion
      of the donor heart ex vivo did not affect the development of CAV.

PMID- 18096481
TI  - Lung transplantation in the management of patients with lymphangioleiomyomatosis:
      baseline data from the NHLBI LAM Registry.
AB  - BACKGROUND: In 1997, the National Heart, Lung, and Blood Institute of the
      National Institutes of Health established a Registry to better characterize the
      demographic, clinical, physiologic and radiographic features of patients with
      lymphangioleiomyomatosis (LAM). Herein we report data collected at enrollment
      from patients who had either undergone transplant prior to enrollment, underwent
      transplant during the 5-year study, or were evaluated/wait-listed for lung
      transplant during the 5-year study. METHODS: The LAM Registry enrolled patients
      from six clinical centers between August 1998 and October 2001. On entry,
      patients filled-out questionnaires covering their medical history, symptoms,
      treatment and quality of life (SF-36 and St. George's Respiratory Questionnaire).
      Enrollees underwent blood laboratory work and testing for arterial blood gases
      and pulmonary function. Follow-up was done at 6-month and/or yearly intervals.
      Diagnoses were confirmed by biopsy or typical clinical presentation plus
      computerized tomography (CT) findings confirmed by independent expert
      radiologists. A total of 243 women were enrolled. Of these, 13 (5.3%) had been
      transplanted at time of entry (Group A), 21 (8.6%) were transplanted during the
      study (Group B), and 48 (19.8%) were either wait-listed for transplant or
      underwent evaluation after enrollment during the study period (Group C). The
      remaining 161 (66.3%) registrants were neither considered for nor listed for
      transplant during the Registry period (Group D). RESULTS: One-third of patients
      in a large sample of LAM patients had either been transplanted or were being
      considered for transplant. At enrollment, patients who had already been
      transplanted and those not in need of transplant (Groups A and D) had better
      pulmonary function and quality-of-life scores compared with patients who
      subsequently underwent lung transplant during the Registry period (Group B).
      CONCLUSIONS: In this large Registry of LAM patients, lung transplantation appears
      to be associated both with significantly improved lung function and quality of
      life compared with patients with advanced disease.

PMID- 18096482
TI  - Dynamics of nitroglycerin-induced exhaled nitric oxide after lung
      transplantation: evidence of pulmonary microvascular injury?
AB  - BACKGROUND: In search of real-time molecular correlates to ischemia-reperfusion
      induced lung injury, we explored the hypothesis that liberation of nitric oxide
      (NO) into exhaled breath after pulmonary microvascular bioconversion of
      nitroglycerin (GTN) is attenuated in clinical lung transplantation. METHODS:
      Exhaled NO was measured under basal conditions and after intravenous
      administration of GTN in patients undergoing lung transplantation. Patients
      undergoing routine cardiac surgery served as controls. Basal and GTN-induced
      exhaled NO was also measured in donors before retrieval and after implantation in
      recipients. RESULTS: The characteristic GTN-induced exhaled NO response observed
      in cardiac surgical patients before cardiopulmonary bypass and in lung transplant
      and multiple-organ donors was nearly totally abolished in lung transplant
      recipients. This response was also attenuated to a lesser degree in the routine
      cardiac surgery patients after cardiopulmonary bypass. CONCLUSIONS: These results
      suggest a graded influence of time-factored complete and partial ischemia on GTN
      induced evolution of NO into exhaled breath, providing biochemical evidence for a
      degree of microvascular injury, which can be monitored non-invasively at the
      bedside.

PMID- 18096483
TI  - Longitudinal changes in heart rate recovery after maximal exercise in pediatric
      heart transplant recipients: evidence of autonomic re-innervation?
AB  - BACKGROUND: Cardiac autonomic innervation modulates heart rate (HR) response
      during and HR recovery after exercise in normal subjects. Heart transplantation
      results in surgical interruption of autonomic innervation. We assessed whether HR
      response during exercise and HR recovery after exercise in pediatric heart
      transplant recipients are consistent with autonomic denervation of the heart
      after transplant and whether they evolve over years in a manner consistent with
      autonomic re-innervation. METHODS: We compared HR response during and HR recovery
      after a maximum treadmill exercise test in 35 children (median age 13.4 years)
      after a median follow-up of 1 year after heart transplant with two control
      groups: post-operative Fontan patients (n = 31) and normal children (n = 35). We
      then analyzed 153 treadmill exercise tests performed serially in 45 heart
      transplant recipients (median 3 tests/patient) for longitudinal changes in peak
      HR and HR recovery after exercise. RESULTS: Transplant recipients had higher body
      mass index, higher resting HR and significantly attenuated 1- and 3-minute HR
      recovery after cessation of exercise compared with both control groups (p <
      0.001). In transplant recipients with serial exercise tests, peak HR increased an
      average of 2.0 beats/min per year after transplant (p < 0.001), percent predicted
      peak HR increased by 1.3% per year (p < 0.001), 1-minute HR recovery increased by
      1.0 beats/min per year (p < 0.001), and 3-minute HR recovery by 2.6 beats/min per
      year (p < 0.001). CONCLUSIONS: HR response to exercise and HR recovery after
      exercise in pediatric heart transplant recipients are consistent with autonomic
      denervation after transplant and suggestive of late autonomic re-innervation of
      these hearts.

PMID- 18096484
TI  - Rapid progression of left ventricular wall thickness predicts mortality in
      cardiac light-chain amyloidosis.
AB  - BACKGROUND: Cardiac amyloidosis (CA) is the most problematic cause of heart
      failure because medical treatment strategies are not well tolerated. Due to its
      high mortality, identification of patients at high risk is crucial for treatment
      strategies such as heart transplantation prior to chemotherapy for amyloid
      disease. METHODS: Left ventricular wall thickness (LVT) progression was
      retrospectively compared with electrocardiographic and echocardiographic
      parameters for risk prediction in 39 patients with histologically proven cardiac
      amyloidosis. RESULTS: Seventeen deaths occurred, equivalent to 1- and 3-year
      survival rates of 62.1% and 55.0%, respectively. LVT progression in deceased
      patients was 2.02 +/- 0.85 mm/month compared with 0.19 +/- 0.03 mm/month in
      survivors (p < 0.001). Autologous stem-cell transplantation (n = 22, or 54%)
      reduced LVT progression as compared with not receiving stem cells (0.21 +/- 0.04
      mm/month vs 1.45 +/- 0.57 mm/month, p < 0.005). LVT progression correlated with
      maximal LVT and absolute LVT increase. Progression of LVT was more rapid in
      patients with impaired LV ejection fraction (LVEF) than preserved LVEF (2.16 +/-
      1.04 mm/month vs 0.30 +/- 0.13 mm/month, p < 0.001). LVT closely correlated with
      survival, whereas initial, maximum or absolute increase in LVT did not. Further
      predictors of survival were LVEF, autologous stem-cell transplantation and low
      voltage, but not diastolic dysfunction. Multivariate analysis identified LVT
      progression as the strongest independent parameter for survival. CONCLUSIONS: LVT
      progression is a powerful risk predictor in light-chain CA, superior to
      parameters such as LVEF, LVT or a low-voltage pattern. Improved survival by high
      dose chemotherapy and stem-cell transplantation is paralleled by a reduction in
      LVT progression. Repetitive echocardiographic assessment appears indicated in CA
      patients to identify candidates for heart transplantation in amyloidosis.

PMID- 18096485
TI  - Ischemically damaged heart after preservation by the cavitary two-layer method as
      a possible donor in rat heart transplantation.
AB  - BACKGROUND: The purpose of this study was to examine the possibility of using an
      ischemically damaged heart, after preservation by the cavitary two-layer (CTL)
      method, as a donor in heart transplantation. METHODS: Each donor heart was
      heterotopically transplanted to the recipient aorta. The grafts in Group 1 were
      immediately transplanted. In Group 2, the grafts with (a) 15- or (b) 30-minute
      warm ischemia were transplanted. The ischemically damaged grafts were
      transplanted after preservation for 3 hours in University of Wisconsin (UW)
      solution (Group 3) or CTL (Group 4). Five-day animal survival, tissue adenine
      triphosphate (ATP) concentration, biochemical assay and histopathologic data were
      obtained. RESULTS: Five-day survival in Group 4a was 7 of 8, with significant
      recovery of the ATP tissue level (9.31 +/- 0.80 micromol/dry weight). Biochemical
      and pathologic examinations demonstrated that ischemia-reperfusion injury was
      prevented in Group 4a compared with Group 2a. CONCLUSIONS: An ischemically
      damaged rat heart preserved for 3 hours by CTL was found to be a potential donor
      in rat heart transplantation.

PMID- 18096486
TI  - N-acetyl cysteine pre-treatment attenuates inflammatory changes in the warm
      ischemic murine lung.
AB  - BACKGROUND: The warm ischemic period in non-heart-beating donor lungs may
      contribute to a higher degree of ischemia-reperfusion injury after lung
      transplantation. We investigated the impact and timing of administration of N
      acetyl cysteine (NAC) on inflammatory parameters. METHODS: Ischemia (I) was
      induced by clamping the hilum of the left lung for 90 minutes, and some protocols
      were followed by reperfusion (R) for 4 hours. Mice were divided into nine groups
      (n = 6/group): three control groups ([sham] (thoracotomy only), [I] and [I+R]);
      two groups with saline instillation only ([saline+I] and [saline+I+R]); and four
      experimental groups with NAC (50 mg/kg), administered by instillation ([NAC+I],
      [NAC+I+R] and [I+NAC+R]) or by aerosol ([NACaero+I+R]). Cell counts and protein
      levels in bronchoalveolar lavage (BAL) were determined. RESULTS: NAC administered
      prior to hilar clamping led to a significant decrease in macrophages and
      lymphocytes and interleukin (IL)-1 beta levels after ischemia. NAC also resulted
      in significantly fewer macrophages, lymphocytes and neutrophils as well as IL-1
      beta, keratinocyte cytokine (KC), monocyte chemoattractant protein (MCP)-1 and IL
      6 levels in BAL taken after reperfusion. CONCLUSIONS: NAC treatment prior to warm
      ischemia attenuates inflammatory changes after both the ischemic and reperfusion
      periods.

PMID- 18096487
TI  - Cardiac re-synchronization therapy in a child with severe anthracycline-induced
      congestive heart failure and normal QRS duration.
AB  - We report the case of a 9-year-old girl who developed acute anthracycline-induced
      cardiotoxicity with severe, refractory congestive heart failure. Rescue treatment
      with cardiac re-synchronization therapy was initiated, resulting in rapid
      improvement in left ventricular function and clinical status.

PMID- 18096488
TI  - Implantable cardioverter-defibrillator implantation as a bridge to cardiac
      transplantation.
AB  - Implantable cardioverter-defibrillators (ICDs) have been shown to reduce sudden
      cardiac death in select patients with impaired left ventricular function.
      However, consensus guidelines on ICD use have not historically addressed patients
      waiting for heart transplantation, and further evidence is needed to broaden and
      strengthen current recommendations. The objective of the present study was to
      review all patients listed for heart transplantation at a single institution and
      evaluate the impact of ICD implantation while waiting. All consecutive patients
      listed for heart transplantation at the Queen Elizabeth II Health Sciences
      Center, Halifax, Nova Scotia, from 1995 to July 2006, were included in the study
      (n = 124). We observed 12 deaths while waiting among patients listed for
      transplantation (10%), with all deaths occurring in the non-ICD patients. In
      patients who did have an ICD prior to transplantation, 17% received appropriate
      defibrillation therapy while awaiting transplantation, and 3 of 12 patients in
      the non-ICD population who died while waiting died suddenly, suggesting that ICDs
      could be used as a "bridge to transplantation" in patients with refractory heart
      failure who are to be listed for heart transplantation.

PMID- 18096489
TI  - Fatal diffuse alveolar damage in two lung transplant patients treated with
      cetuximab.
AB  - Organ transplant recipients are at increased risk for aggressive cutaneous
      squamous cell carcinomas (cSCC) that recur and metastasize despite treatment with
      surgery, radiation, or both. Therapies targeting the epidermal growth factor
      receptor (EGFR) are being explored as treatments for metastatic cSCC. We describe
      our experience with two single-lung transplant patients who developed metastatic
      cSCC; failed surgical resection, radiation or chemoradiation therapy; and were
      ultimately treated with an EGFR inhibitor, cetuximab. Both patients died shortly
      after initiation of cetuximab due to diffuse alveolar damage, suggesting that
      EGFR inhibitors should be used with extreme caution in lung transplant
      recipients.

PMID- 18096490
TI  - Bosentan treatment in an adult with pulmonary hypertension due to patent ductus
      arteriosus permits surgical repair.

PMID- 18096491
TI  - Pre-operative long-term optimization with prostanoids in initially inoperable
      severe chronic thromboembolic pulmonary hypertension (CTEPH): a step forward?

PMID- 18096492
TI  - Visceral leishmaniasis in an Italian heart recipient: first case report.

PMID- 18096493
TI  - Relationship between coronary microcirculatory dysfunction and left ventricular
      long-axis function in heart transplant recipients.

PMID- 18096494
TI  - Hypogammaglobulinemia in heart failure patients: prevalence and impact on
      infectious outcomes.

PMID- 18096495
TI  - Tackling type 1 diabetes: new immune-modulating drugs attack the root cause.

PMID- 18096496
TI  - Jekyll & Hyde: evolution of a superfamily.
AB  - Aminoacyl-tRNA synthetase mutations have been linked to neurological diseases,
      but aminoacylation may be unaffected. This protein superfamily also performs many
      other diverse functions. Yang et al. insightfully engineer a single mutation to
      unmask a cell signaling activity of tyrosyl-tRNA synthetase.

PMID- 18096497
TI  - 2-AG + 2 new players = forecast for therapeutic advances.
AB  - In this issue of Chemistry & Biology, Blankman et al. identify new enzymes
      hydrolyzing the endocannabionoid 2-arachidonoyl glycerol (2-AG), increasing the
      complexity of endocannabinoid signaling in the brain, but also pinpointing
      additional therapeutic targets.

PMID- 18096498
TI  - Fatty pain cures.
AB  - In this issue, Alvin King, Daniele Piomelli, and colleagues publish another
      interesting paper on inhibition of monoacylglycerol lipase (MGL). MGL is a hot
      target for antinociceptive agents, being the chief degrading enzyme of the
      endocannabinoid 2-arachidonoylglycerol.

PMID- 18096499
TI  - Emetine and the alternative splicing of Bcl-X: where to next?
AB  - Interference with the alternative splicing of apoptotic factors offers an
      innovative and specific mechanism to target malignant cells. In this issue of
      Chemistry & Biology, Zhou et al. report on the regulation of the alternative
      splicing of Bcl-x pre-mRNA in response to emetine, a potent protein synthesis
      inhibitor, as well as define a major player in the signaling mechanism.

PMID- 18096500
TI  - Synthesis of polyester by means of genetic code reprogramming.
AB  - Here we report the ribosomal polymerization of alpha-hydroxy acids by means of
      genetic code reprogramming. The flexizyme system, a ribozyme-based tRNA acylation
      tool, was used to re-assign individual codons to seven types of alpha-hydroxy
      acids, and then polyesters were synthesized under controls of the reprogrammed
      genetic code using a reconstituted cell-free translation system. The sequence and
      length of the polyester segments were specified by the mRNA template, indicating
      that high-fidelity ribosome expression of polyesters was possible. This work
      opens a door for the mRNA-directed synthesis of backbone-altered biopolymers.

PMID- 18096501
TI  - Gain-of-function mutational activation of human tRNA synthetase procytokine.
AB  - Disease-causing mutations occur in genes for aminoacyl tRNA synthetases. That
      some mutations are dominant suggests a gain of function. Native tRNA synthetases,
      such as tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase,
      catalyze aminoacylation and are also procytokines that are activated by natural
      fragmentation. In principle, however, gain-of-function phenotypes could arise
      from mutational activation of synthetase procytokines. From crystal structure
      analysis, we hypothesized that a steric block of a critical Glu-Leu-Arg (ELR)
      motif in full-length TyrRS suppresses the cytokine activity of a natural
      fragment. To test this hypothesis, we attempted to uncover ELR in the procytokine
      by mutating a conserved tyrosine (Y341) that tethers ELR. Site-specific
      proteolytic cleavage and small-angle X-ray scattering established subtle opening
      of the structure by the mutation. Strikingly, four different assays demonstrated
      mutational activation of cytokine functions. The results prove the possibilities
      for constitutive gain-of-function mutations in tRNA synthetases.

PMID- 18096502
TI  - A squalene epoxidase is involved in biosynthesis of both the antitumor compound
      clavaric acid and sterols in the basidiomycete H. sublateritium.
AB  - The basidiomycete Hypholoma sublateritium produces the triterpenoid antitumor
      clavaric acid, an inhibitor of the human Ras-farnesyl transferase. The H.
      sublateritium squalene epoxidase gene (erg1) has been cloned and shown to encode
      a flavoprotein monooxygenase that requires FAD, NADPH, and P450 cofactors.
      Silencing of the erg1 gene in H. sublateritium using constructions expressed from
      the gdh promoter of Agaricus bisporus showed that the squalene epoxidase is
      involved in clavaric acid formation and in ergosterol biosynthesis; silenced
      expression of erg1 resulted in an ergosterol-dependent phenotype for full growth.
      Overexpression of erg1 gene resulted in up to 32% to 97% increment of clavaric
      acid production confirming its involvement in the biosynthesis of this antitumor
      product. Oxidosqualene (or dioxidosqualene) appears to be the branching point for
      primary metabolism (sterols) and secondary metabolites in basidiomycetes.

PMID- 18096503
TI  - A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2
      arachidonoylglycerol.
AB  - Endogenous ligands for cannabinoid receptors ("endocannabinoids") include the
      lipid transmitters anandamide and 2-arachidonoylglycerol (2-AG). Endocannabinoids
      modulate a diverse set of physiological processes and are tightly regulated by
      enzymatic biosynthesis and degradation. Termination of anandamide signaling by
      fatty acid amide hydrolase (FAAH) is well characterized, but less is known about
      the inactivation of 2-AG, which can be hydrolyzed by multiple enzymes in vitro,
      including FAAH and monoacylglycerol lipase (MAGL). Here, we have taken a
      functional proteomic approach to comprehensively map 2-AG hydrolases in the mouse
      brain. Our data reveal that approximately 85% of brain 2-AG hydrolase activity
      can be ascribed to MAGL, and that the remaining 15% is mostly catalyzed by two
      uncharacterized enzymes, ABHD6 and ABHD12. Interestingly, MAGL, ABHD6, and ABHD12
      display distinct subcellular distributions, suggesting that they may control
      different pools of 2-AG in the nervous system.

PMID- 18096504
TI  - URB602 inhibits monoacylglycerol lipase and selectively blocks 2
      arachidonoylglycerol degradation in intact brain slices.
AB  - The N-aryl carbamate URB602 (biphenyl-3-ylcarbamic acid cyclohexyl ester) is an
      inhibitor of monoacylglycerol lipase (MGL), a serine hydrolase involved in the
      biological deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG).
      Here, we investigated the mechanism by which URB602 inhibits purified recombinant
      rat MGL by using a combination of biochemical and structure-activity relationship
      (SAR) approaches. We found that URB602 weakly inhibits recombinant MGL (IC(50) =
      223 +/- 63 microM) through a rapid and noncompetitive mechanism. Dialysis
      experiments and SAR analyses suggest that URB602 acts through a partially
      reversible mechanism rather than by irreversible carbamoylation of MGL. Finally,
      URB602 (100 microM) elevates 2-AG levels in hippocampal slice cultures without
      affecting levels of other endocannabinoid-related substances. Thus, URB602 may
      provide a useful tool by which to investigate the physiological roles of 2-AG and
      explore the potential interest of MGL as a therapeutic target.

PMID- 18096505
TI  - Arabidopsis P-glycoprotein19 participates in the inhibition of gravitropism by
      gravacin.
AB  - ATP-binding cassette (ABC) transporters have been implicated in a multitude of
      biological pathways. In plants, some ABC transporters are involved in the polar
      transport of the plant hormone auxin and the gravitropic response. We previously
      identified Gravacin as a potent inhibitor of gravitropism in Arabidopsis
      thaliana. We demonstrate that P-glycoprotein19 (PGP19) is a target for Gravacin
      and participates in its inhibition of gravitropism. Gravacin inhibited the auxin
      transport activity of PGP19 and PGP19-PIN complexes. Furthermore, we identified
      E1174 as an important residue for PGP19 activity and its ability to form active
      transport complexes with PIN1. Gravacin is an auxin transport inhibitor that
      inhibits PGPs, particularly PGP19, which can be used to further dissect the role
      of PGP19 without the inhibition of other auxin transporters, namely PIN proteins.

PMID- 18096506
TI  - Catalytic residues are shared between two pseudosubunits of the dehydratase
      domain of the animal fatty acid synthase.
AB  - Expression, characterization, and mutagenesis of a series of N-terminal fragments
      of an animal fatty acid synthase, containing the beta-ketoacyl synthase, acyl
      transferase, and dehydratase domains, demonstrate that the dehydratase domain
      consists of two pseudosubunits, derived from contiguous regions of the same
      polypeptide, in which a single active site is formed by the cooperation of the
      catalytic histidine 878 residue of the first pseudosubunit with aspartate 1032 of
      the second pseudosubunit. Mutagenesis and modeling studies revealed an essential
      role for glutamine 1036 in anchoring the position of the catalytic aspartate.
      These findings establish that sequence elements previously assigned to a central
      structural core region of the type I fatty acid synthases and some modular
      polyketide synthase counterparts play an essential catalytic role as part of the
      dehydratase domain.

PMID- 18096508
TI  - Review of traffic accident cases presenting to an adult emergency service in
      Turkey.
AB  - INTRODUCTION: Traffic accidents cause the death of millions in the world each
      year. Learning about the characteristics of the casualties involved in such
      accidents, which constitute a very important health problem, is essential in
      terms of measures to be taken. They may have substantial humanitarian and
      economic impact. MATERIALS AND METHODS: In this study, injured patients who had
      been involved in traffic accidents presenting to the adult Emergency service of
      Gazi University Hospital (Ankara, Turkey) in the 3-month period between 1st of
      March and 31st of May 2006, were examined, and review of a range of factors
      including the effects of age, gender, mode of transport to the hospital, type and
      regions of injury, time of injury, and presence of factors such as alcohol and
      alike was undertaken. FINDINGS: A total eight thousand and eight hundred patients
      presented to our emergency department within the study period. Two hundred and
      sixty-two (3%) of these patients were injuries sustained in crashes. 38.2% (100)
      of the patients were women, and 61.8% (162) were men. The most frequently
      presenting age group was the under-25 age group with 27.9%. The highest
      attendence in Emergency Medicine Departments due to crashes was the period
      between 18:00h and 24:00h, (34.4% (n=90)). The most frequent presentations were
      of those of patients sitting in the front seats (driver or passenger) with 48.5%
      (n=127). 60.3% (n=158) of the injured were conveyed to the hospital by the
      ambulances of the national emergency call system. The great majority of injuries
      (54.9%, n=149) were patients with multiple traumas- also involving the head and
      the neck regions. Alcohol levels were determined in 59.6% of the cases, and in 19
      cases the alcohol level was found to be higher than the legal limit of 50mg/dL.
      1.1% (n=3) of the injured cases died in the emergency service, 8.4% were
      hospitalized in relevant clinics, 0.8% were referred, and 89.7% (n=235) were
      followed-up in the emergency room for various periods of time, and then
      discharged. CONCLUSION: Traffic accidents constitute a very important health
      problem for the public health. Treatment of the injured individuals, and losses
      from the work force are significant for developing countries like our country.
      Studies directed towards the causes of traffic accidents will play a very
      important role in determining the measures to decrease or prevent such crashes.

PMID- 18096507
TI  - Emetine regulates the alternative splicing of Bcl-x through a protein phosphatase
      1-dependent mechanism.
AB  - Exon 2 of the Bcl-x gene undergoes alternative splicing in which the Bcl-xS
      splice variant promotes apoptosis in contrast to the anti-apoptotic splice
      variant Bcl-xL. In this study, the regulation of the alternative splicing of pre
      mRNA of Bcl-x was examined in response to emetine. Treatment of different types
      of cancer cells with emetine dihydrochloride downregulated the level of Bcl-xL
      mRNA with a concomitant increase in the mRNA level of Bcl-xS in a dose- and time
      dependent manner. Pretreatment with calyculin A, an inhibitor of protein
      phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), blocked emetine-induced
      alternative splicing in contrast to okadaic acid, a specific inhibitor of PP2A in
      cells, demonstrating a PP1-mediated mechanism. Our finding on the regulation of
      RNA splicing of members of the Bcl-2 family in response to emetine presents a
      potential target for cancer treatment.

PMID- 18096509
TI  - Suicidal poisoning in Southern India: gender differences.
AB  - Poisoning is an important health hazard and one of the leading causes of
      morbidity and mortality worldwide. Poisoning is one of the preferred means of
      committing suicide among males and females in India. A five year retrospective
      study from January 2000 to December 2004 was conducted at the Department of
      Forensic Medicine & Toxicology, Kasturba Medical College, Manipal, to understand
      the magnitude and pattern of suicidal poisoning deaths among males and females in
      Southern India. During this period, a total of 137 cases of suicidal poisoning
      related deaths were autopsied. Males were predominantly affected (male:female
      2.8:1). Maximum victims of suicidal poisoning mortalities were in their 3rd
      decade. Mean age for males and females was 40.5 years and 34.4 years,
      respectively. 27.8% of females and 10.9% males were suffering from depression.
      Preference for organophosphates was relatively more in males when compared to
      females, who preferred zinc phosphide, carbamates and medicinal agents. Suicidal
      poisoning was commonly encountered during afternoon hours in females. Males
      usually consumed poison during evening and late night hours. Maximum male
      mortalities were noted during second quarter of the year in contrast to first
      quarter in females. This paper examines the difference in pattern of suicidal
      poisoning among males and females to identify population at risk, and understand
      the problem status among both genders.

PMID- 18096510
TI  - Determining prognosis after spinal cord injury.
AB  - INTRODUCTION: Disability following traumatic spine injury often requires
      assessment for judicial reasons. OBJECTIVE: To determine the optimum time to
      carry out a medico-legal evaluation. METHODS: Retrospective study (1995-2000) of
      patients with traumatic spine injury with a follow-up of five years. The American
      Spinal Injury Association (ASIA) scale was used to determine level and extent of
      the injury. Statistical analysis by SPSS 11.0. RESULTS AND DISCUSSION: 173
      injuries were analyzed (39.3% ASIA A; 15.6% ASIA B; 29.47% ASIA C; 15.6% ASIA D).
      Neurological improvement was detected in 35.83%, more frequently in incomplete
      injuries. ASIA A injuries remained mainly complete from admission to discharge
      and in no case reached functional levels. Only a third of ASIA B patients showed
      improvement, of whom 33.3% were functional. Improvement in ASIA C patients was
      76.4%, these and all ASIA D patients were functional on discharge. The condition
      a year after the injury remained unchanged in all cases, regardless of the extent
      of injury. Patients who showed improvement did so early on, mainly during
      hospitalization. CONCLUSIONS: The optimum time for evaluation of spinal cord
      injury for medicolegal purposes is at one year after the injury. In cases of
      complete injury, evaluation can be carried out on discharge with no need to wait
      for one year.

PMID- 18096511
TI  - Silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase by small
      interfering RNA enhances heat shock-induced apoptosis.
AB  - Heat shock may increase oxidative stress due to increased production of reactive
      oxygen species and/or the promotion of cellular oxidation events. Mitochondrial
      NADP(+)-dependent isocitrate dehydrogenase (IDPm) produces NADPH, an essential
      reducing equivalent for the antioxidant system. In this report, we demonstrate
      that silencing of IDPm expression in HeLa cells greatly enhances apoptosis
      induced by heat shock. Transfection of HeLa cells with an IDPm small interfering
      RNA (siRNA) markedly decreased activity of IDPm, enhancing the susceptibility of
      heat shock-induced apoptosis reflected by morphological evidence of apoptosis,
      DNA fragmentation, cellular redox status, mitochondria redox status and function,
      and the modulation of apoptotic marker proteins. These results indicate that IDPm
      may play an important role in regulating the apoptosis induced by heat shock and
      the sensitizing effect of IDPm siRNA on the apoptotic cell death of HeLa cells
      offers the possibility of developing a modifier of cancer therapy.

PMID- 18096512
TI  - Interaction of human 3-phosphoglycerate kinase with L-ADP, the mirror image of D
      ADP.
AB  - l-Nucleoside-analogues, mirror images of the natural d-nucleosides, are a new
      class of antiviral and anticancer agents. In the cell they have to be
      phosphorylated to pharmacologically active triphosphate forms, the last step
      seems to involve human 3-phosphoglycerate kinase (hPGK). Here we present a steady
      state kinetic and biophysical study of the interaction of the model compound l
      MgADP with hPGK. l-MgADP is a good substrate with k(cat) and K(m) values of 685s(
      1) and 0.27mM, respectively. Double inhibition studies suggest that l-MgADP binds
      to the specific adenosine-binding site and protects the conformation of hPGK
      molecule against heat denaturation, as detected by microcalorimetry. Structural
      details of the interaction in the enzyme active site are different for the d- and
      l-enantiomers (e.g. the effect of Mg(2+)), but these differences do not prevent
      the occurrence of the catalytic cycle, which is accompanied by the hinge-bending
      domain closure, as indicated by SAXS measurements.

PMID- 18096513
TI  - Allosterically coupled calcium and magnesium binding sites are unmasked by
      ryanodine receptor chimeras.
AB  - We studied cation regulation of wild-type ryanodine receptor type 1 ((WT)RyR1),
      type 3 ((WT)RyR3), and RyR3/RyR1 chimeras (Ch) expressed in 1B5 dyspedic
      myotubes. Using [(3)H]ryanodine binding to sarcoplasmic reticulum (SR) membranes,
      Ca(2+) titrations with (WT)RyR3 and three chimeras show biphasic activation that
      is allosterically coupled to an attenuated inhibition relative to (WT)RyR1.
      Chimeras show biphasic Mg(2+) inhibition profiles at 3 and 10 microM Ca(2+), no
      observable inhibition at 20 microM Ca(2+) and monophasic inhibition at 100 microM
      Ca(2+). Ca(2+) imaging of intact myotubes expressing Ch-4 exhibit caffeine
      induced Ca(2+) transients with inhibition kinetics that are significantly slower
      than those expressing (WT)RyR1 or (WT)RyR3. Four new aspects of RyR regulation
      are evident: (1) high affinity (H) activation and low affinity (L) inhibition
      sites are allosterically coupled, (2) Ca(2+) facilitates removal of the inherent
      Mg(2+) block, (3) (WT)RyR3 exhibits reduced cooperativity between H activation
      sites when compared to (WT)RyR1, and (4) uncoupling of these sites in Ch-4
      results in decreased rates of inactivation of caffeine-induced Ca(2+) transients.

PMID- 18096515
TI  - Low temperature induces the delivery of mature and immature CFTR to the plasma
      membrane.
AB  - Deletion of phenylalanine 508 (DeltaF508) is the most prevalent disease-causing
      mutation resulting in retention of the immature CFTR in the endoplasmic
      reticulum. The most common strategy to induce the delivery of DeltaF508-CFTR to
      the surface of cells is by reducing the incubation temperature ( approximately 28
      degrees C). Cell surface biotinylation of HEK293T cells grown at 37 degrees C for
      48h, confirmed the presence of mature wild-type CFTR, but not DeltaF508-CFTR at
      the cell surface. On the other hand, cells incubated at 28 degrees C for 16h
      showed both mature and immature DeltaF508-CFTR at their surface. The trafficking
      of immature DeltaF508-CFTR, but not mature DeltaF508-CFTR, to the cell surface
      occurred at low temperature even upon addition of BFA, suggesting the involvement
      of a Golgi-independent pathway. These results suggest that low temperature
      induces the appearance of a mix population of mature and immature CFTR molecules
      at the plasma membrane through distinct pathways.

PMID- 18096514
TI  - Inhibition of APP intracellular domain (AICD) transcriptional activity via
      covalent conjugation with Nedd8.
AB  - The processing of amyloid precursor protein (APP) by gamma-secretase generates
      the APP intracellular domain (AICD), which functions as a transcriptional factor
      for target gene activation following localization into the nucleus. In this
      study, we demonstrate that AICD could be modified via covalent conjugation with
      Nedd8, a ubiquitin-like protein. Domain analysis and site-directed substitution
      of neddylation sites showed that multiple lysine residues of the APP C-terminal
      C99 fragment including AICD were acceptor sequences for Nedd8 conjugation. AICD
      mediated transcriptional activation was inhibited by Nedd8 conjugation.
      Furthermore, the transcriptional activity of the neddylation-defective AICD
      mutant was not altered by Nedd8 expression. Nedd8 conjugation of AICD inhibited
      its interaction with Fe65, and consequently resulted in the impairment of AICD
      Fe65-Tip60 complex formation for the transcriptional activation of the target
      gene. These results illustrate the regulatory mechanisms by which AICD
      transcriptional activity might be regulated via covalent conjugation with Nedd8.

PMID- 18096516
TI  - Functional role of the conserved proline in helix 6 of the human bradykinin B2
      receptor.
AB  - Pro258 in transmembrane domain (TMD) 6 of the bradykinin (BK) B(2) receptor
      (B(2)R) is highly conserved among G-protein coupled receptors (GPCRs). Using
      mutagenesis, we show that Pro258 is required for normal trafficking of the
      receptor to the plasma membrane and that mutation of Pro258 to Ala or Leu but not
      Gly, enhances BK efficacy to induce receptor activation. Furthermore, P258A
      mutation suppresses the constitutive activity of a constitutively activated N113A
      B(2)R mutant but preserves the antagonist to agonist efficacy shift previously
      observed on the N113A single mutant. Our data suggest that Pro258 in TMD6 is
      required for agonist-independent activation of the B(2)R and that straightening
      of TMD6 at the Pro-kink might favor G-protein coupling. It is also shown that
      Asn113 is a contact point of BK interaction and it is proposed that the release
      of a TMD3-TMD6 interaction involving Asn113 is crucial for the efficacy shift
      from antagonism toward agonism.

PMID- 18096517
TI  - Spotlight on... Hans Eklund. Interview by Daniela Ruffell.

PMID- 18096518
TI  - Collagen binding is a key factor for the hemorrhagic activity of snake venom
      metalloproteinases.
AB  - Snake venom metalloproteinases (SVMPs) are multifunctional enzymes involved in
      several symptoms following snakebite, such as severe local hemorrhage.
      Multidomain P-III SVMPs are strongly hemorrhagic, whereas single domain P-I SVMPs
      are not. This indicates that disintegrin-like and cysteine-rich domains allocate
      motifs that enable catalytic degradation of ECM components leading to disruption
      of capillary vessels. Interestingly, some P-III SVMPs are completely devoid of
      hemorrhagic activity despite their highly conserved disintegrin-like and cysteine
      rich domains. This observation was approached in the present study by comparing
      the effects of jararhagin, a hemorrhagic P-III SVMP, and berythractivase, a pro
      coagulant and non-hemorrhagic P-III SVMP. Both toxins inhibited collagen-induced
      platelet aggregation, but only jararhagin was able to bind to collagen I with
      high affinity. The monoclonal antibody MAJar 3, that neutralizes the hemorrhagic
      effect of Bothrops venoms and jararhagin binding to collagen, did not react with
      berythractivase. The three-dimensional structures of jararhagin and
      berythractivase were compared to explain the differential binding to collagen and
      MAJar 3. Thereby, we pinpointed a motif within the Da disintegrin subdomain
      located opposite to the catalytic domain. Jararhagin binds to both collagen I and
      IV in a triple helix-dependent manner and inhibited in vitro fibrillogenesis. The
      jararhagin-collagen complex retained the catalytic activity of the toxin as
      observed by hydrolysis of fibrin. Thus, we suggest that binding of hemorrhagic
      SVMPs to collagens I and IV occurs through a motif located in the Da subdomain.
      This allows accumulation of toxin molecules at the site of injection, close to
      capillary vessels, where their catalytic activity leads to a local hemorrhage.
      Toxins devoid of this motif would be more available for vascular internalization
      leading to systemic pro-coagulant effects. This reveals a novel function of the
      disintegrin domain in hemorrhage formation.

PMID- 18096519
TI  - Post mortem survey of dental disorders in 349 donkeys from an aged population
      (2005-2006). Part 1: prevalence of specific dental disorders.
AB  - REASON FOR PERFORMING STUDY: Donkey dental disorders are being recognised with
      increased frequency worldwide and have important welfare implications; however,
      no detailed investigations of dental disorders in donkeys appear to have been
      published. OBJECTIVES: To determine the prevalence of specified dental disorders
      in donkeys by performing a prospective post mortem study on donkeys that were
      subjected to euthanasia or died for other reasons at the Donkey Sanctuary, UK.
      METHODS: Post mortem examinations were performed on 349 donkeys over an 18 month
      period, 2005-2006. The presence and extent of specified dental disorders were
      recorded and these data analysed to determine their prevalence and common
      locations. RESULTS: A high prevalence (93%) of disorders was noted in the
      population with a median age of 31 years. In particular, cheek teeth diastemata
      (85% prevalence) were very common, often associated with advanced periodontal
      disease. Other disorders observed included missing teeth (in 55.6% of donkeys),
      displaced teeth (43%), worn teeth (34%), local overgrowths (15%), focal sharp
      overgrowths (3%) and dental-related soft tissue injuries (8%). CONCLUSIONS AND
      POTENTIAL RELEVANCE: Aged donkeys have a high prevalence of significant dental
      disease, especially cheek teeth diastemata. These findings highlight the
      importance of routine dental examinations and prophylactic dental treatments to
      improve the dental health and welfare of donkeys.

PMID- 18096520
TI  - What is the value of measuring coronary artery calcification?

PMID- 18096524
TI  - Hand hygiene.

PMID- 18096526
TI  - Imaging genetics of brain longevity and mental wellness: the next frontier?
AB  - The advent of new "omics" technologies (genomics, proteomics, and metabolomics)
      has ushered in a new era of biomedical discovery that is already affecting every
      field of medicine. With the rapid growth of the older population worldwide, there
      is great interest in applying these technologies not only to diagnose and prevent
      disease, but also to enhance brain longevity and mental wellness. Nearly two
      thirds of the approximately 30,000 genes in the human genome are related to brain
      function, and up to half of the variance in age-related changes in cognition,
      brain volume, and neuronal function appears to be genetically determined.
      Selected examples will be used to illustrate how neuroimaging is being employed
      to study the effects of genes and how neurogenetics may affect future radiology
      research and practice.

PMID- 18096527
TI  - Double-contrast upper gastrointestinal radiography: a pattern approach for
      diseases of the stomach.
AB  - The double-contrast upper gastrointestinal series is a valuable diagnostic test
      for evaluating structural and functional abnormalities of the stomach. This
      article will review the normal radiographic anatomy of the stomach. The
      principles of analyzing double-contrast images will be discussed. A pattern
      approach for the diagnosis of gastric abnormalities will also be presented,
      focusing on abnormal mucosal patterns, depressed lesions, protruded lesions,
      thickened folds, and gastric narrowing.

PMID- 18096528
TI  - RadiologyInfo: reaching out to touch patients.
AB  - RadiologyInfo is a public information Web site created and maintained as an
      unprecedented joint collaborative effort of the Radiological Society of North
      America and the American College of Radiology. Conceived in 1997 and operating
      since 2000, the site has grown to become a leading medical information site,
      currently with more than 100 radiologic examinations and treatments described.
      Each month, well over half a million visitors connect to RadiologyInfo (660,000
      visits in March 2007). The information is now also available in Spanish and
      French. New procedures, current topics, and additional images are added on an
      ongoing basis.

PMID- 18096529
TI  - Mammographic, US, and MR imaging phenotypes of familial breast cancer.
AB  - PURPOSE: To prospectively investigate the imaging (mammographic, ultrasonographic
      [US], magnetic resonance [MR] imaging) features of invasive and intraductal
      breast cancers in women at familial risk. MATERIALS AND METHODS: Ethics committee
      approval and informed consent were obtained. Breast cancers were identified in
      women at moderately increased risk, in women at high familial risk, and in
      documented BRCA1 and BRCA2 mutation carriers. All cancers were investigated with
      mammography, US, and bilateral dynamic breast MR imaging. Imaging findings of
      breast cancer in women in the different risk categories were prospectively
      collected and compared. With the two-sample Wilcoxon signed rank test, imaging
      features of cancers were compared. RESULTS: Seventy-six breast cancers were
      identified in 68 women (mean age, 41.3 years). Mammographic breast density had no
      influence on detectability of cancers. Imaging phenotypes differed among risk
      categories: 15 (23%) of 64 invasive cancers appeared as fibroadenoma-like masses
      without calcifications but without fibroadenoma-like internal enhancement or
      enhancement kinetics at breast MR imaging. Of those, 12 (80%) occurred in women
      at high risk and documented BRCA1 mutation carriers. A posterior (immediately
      prepectoral) location was observed in 67% (32 of 48) of all breast cancers in
      women at high risk and mutation carriers (P < .009). None of the remaining BRCA1
      associated invasive cancers exhibited calcifications; intraductal cancers were
      not observed. In 28 cancers in BRCA2 carriers or women at moderately increased
      risk, imaging features seemed equivalent to those reported for sporadic cancers;
      cases of ductal carcinoma in situ were observed, and there was no preference for
      a posterior location in the breast. At MR imaging, a high percentage (20% [13 of
      64]) of invasive cancers appeared as non-masslike enhancement; benign kinetic
      features were observed in 33% (25 of 76). CONCLUSION: Imaging phenotypes of
      cancers differ among risk categories. If MR imaging is used for screening, high
      sensitivity rates are achievable only if morphologic and kinetic features are
      assessed and if non-masslike enhancement is considered. Lesion location is
      important in regard to malignancy. SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/246/1/58/DC1.

PMID- 18096530
TI  - Computer-aided detection in full-field digital mammography: sensitivity and
      reproducibility in serial examinations.
AB  - PURPOSE: To retrospectively evaluate the sensitivity and reproducibility of a
      computer-aided detection (CAD) system applied to serial digital mammograms
      obtained in women with breast cancer, with histologic analysis as the reference
      standard. MATERIALS AND METHODS: This study was institutional review board
      approved, and patient informed consent was waived. A commercially available CAD
      system was applied to initial and follow-up digital mammograms obtained in 93
      women with breast cancer (mean age, 52 years; age range, 32-81 years). The mean
      interval between mammographic examinations was 23 days (range, 7-58 days). There
      were 119 visible lesion components (70 masses, 49 microcalcifications).
      Sensitivity, false-positive mark rate, and reproducibility of the CAD system were
      evaluated for both sets of mammograms with the t test. RESULTS: Sensitivities of
      the CAD system at initial and follow-up digital mammography were 91% and 89%,
      respectively, for detection of masses. Sensitivity of the CAD system for
      detection of microcalcifications was 100% at both initial and follow-up digital
      mammography. Overall false-positive mark rates were 0.29 per image and 0.27 per
      image at initial and follow-up digital mammography, respectively. When
      craniocaudal and mediolateral oblique views were considered separately,
      sensitivities were 76% and 75%, respectively, for masses and 96% and 92%,
      respectively, for microcalcifications. The reproducibility of CAD marks was 80%
      for true-positive masses, 92% for true-positive microcalcifications, 9% for false
      positive masses, and 8% for false-positive microcalcifications (P < .001).
      CONCLUSION: The sensitivity of the CAD system was consistently high for detection
      of breast cancer on initial and short-term follow-up digital mammograms.
      Reproducibility was significantly higher for true-positive CAD marks than for
      false-positive CAD marks. SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/246/1/71/DC1.

PMID- 18096532
TI  - Saline flush effect for enhancement of aorta and coronary arteries at
      multidetector CT coronary angiography.
AB  - PURPOSE: To prospectively investigate the effect of the injection rate of a
      saline solution as a bolus chaser for the enhancement of the aorta and coronary
      arteries at multidetector computed tomographic (CT) coronary angiography.
      MATERIALS AND METHODS: Institutional review board approved this study, and all
      patients gave informed consent. One hundred consecutive patients (59 men, 41
      women; mean age, 58 years +/- 11 [standard deviation]) underwent 64-section CT
      coronary angiography for coronary artery disease. They were divided into five
      groups (each group, n = 20) according to the injection rate of saline solution
      (3, 4, 5, 6, and 7 mL/sec). Iodinated contrast medium (60 mL) was injected
      intravenously at a rate of 4 mL/sec, followed by 60 mL saline solution
      administered intravenously at a rate of 3-7 mL/sec, depending on the groups.
      Attenuation values of the aortic root, right coronary artery, left anterior
      descending artery, and left circumflex artery were measured. Analysis of variance
      with the Scheffe method was used to evaluate statistical significance of the
      differences in attenuation according to the injection rate of saline solution.
      RESULTS: The degree of contrast enhancement was affected by the injection rate of
      saline solution, and the attenuation values were higher as the injection rate
      increased up to 4-5 mL/sec (P < .05). The values plateaued at rates over 5 mL/sec
      in the aorta and over 4 mL/sec in the coronary arteries. CONCLUSION: An injection
      rate of 4-5 mL/sec as a saline solution chaser is optimal for achieving maximum
      attenuation values of the aorta or coronary arteries by using 64-section CT with
      60 mL contrast material.

PMID- 18096533
TI  - Hypervascular liver tumors: low tube voltage, high tube current multi-detector
      row CT for enhanced detection--phantom study.
AB  - PURPOSE: To prospectively evaluate, for the depiction of simulated hypervascular
      liver lesions in a phantom, the effect of a low tube voltage, high tube current
      computed tomographic (CT) technique on image noise, contrast-to-noise ratio
      (CNR), lesion conspicuity, and radiation dose. MATERIALS AND METHODS: A custom
      liver phantom containing 16 cylindric cavities (four cavities each of 3, 5, 8,
      and 15 mm in diameter) filled with various iodinated solutions to simulate
      hypervascular liver lesions was scanned with a 64-section multi-detector row CT
      scanner at 140, 120, 100, and 80 kVp, with corresponding tube current-time
      product settings at 225, 275, 420, and 675 mAs, respectively. The CNRs for six
      simulated lesions filled with different iodinated solutions were calculated. A
      figure of merit (FOM) for each lesion was computed as the ratio of CNR2 to
      effective dose (ED). Three radiologists independently graded the conspicuity of
      16 simulated lesions. An anthropomorphic phantom was scanned to evaluate the ED.
      Statistical analysis included one-way analysis of variance. RESULTS: Image noise
      increased by 45% with the 80-kVp protocol compared with the 140-kVp protocol (P <
      .001). However, the lowest ED and the highest CNR were achieved with the 80-kVp
      protocol. The FOM results indicated that at a constant ED, a reduction of tube
      voltage from 140 to 120, 100, and 80 kVp increased the CNR by factors of at least
      1.6, 2.4, and 3.6, respectively (P < .001). At a constant CNR, corresponding
      reductions in ED were by a factor of 2.5, 5.5, and 12.7, respectively (P < .001).
      The highest lesion conspicuity was achieved with the 80-kVp protocol. CONCLUSION:
      The CNR of simulated hypervascular liver lesions can be substantially increased
      and the radiation dose reduced by using an 80-kVp, high tube current CT
      technique.

PMID- 18096534
TI  - Cartilage thickness: factors influencing multidetector CT measurements in a
      phantom study.
AB  - PURPOSE: To prospectively assess in a phantom the reconstruction errors and
      detection limits of cartilage thickness measurements obtained with multidetector
      computed tomographic (CT) arthrography, as a function of contrast agent
      concentration, scanning direction, spatial resolution, joint spacing, and tube
      current, with known measurements as the reference standard. MATERIALS AND
      METHODS: A phantom with nine chambers was constructed. Each chamber had a nylon
      cylinder encased by sleeves of aluminum and polycarbonate to simulate trabecular
      bone, cortical bone, and cartilage. Varying simulated cartilage thicknesses and
      10 joint space widths were assessed. On 3 days, the phantom was scanned with and
      without contrast agent administration and with the chamber axes both
      perpendicular and parallel to the scanner axis. Images were reconstructed at 1.0-
      and 0.5-mm intervals. Contrast agent concentration and tube current were varied.
      The simulated cartilage thickness was determined by using image segmentation.
      Root mean squared errors and mean residual errors were used to characterize the
      measurements. The reproducibility of the CT scanner and image segmentation
      results was determined. RESULTS: Simulated cartilage greater than 1.0 mm in
      thickness was reconstructed with less than 10% error when either no contrast
      agent or a low concentration (25%) of contrast agent was used. Error increased as
      contrast agent concentration increased. Decreasing the simulated joint space
      width to 0.5 mm caused slight increases in error; however, error increased
      substantially at joint spaces narrower than 0.5 mm. Errors in measurements
      derived from anisotropic CT data were greater than errors in measurements derived
      from isotropic data. Altering the tube current did not substantially affect
      reconstruction errors. CONCLUSION: The study revealed lower boundaries and the
      repeatability of simulated cartilage thickness measurements obtained by using
      multidetector CT arthrography and yielded data pertinent to choosing the contrast
      agent concentration, joint space width, scanning direction, and spatial
      resolution to reduce reconstruction errors.

PMID- 18096535
TI  - Perforated and nonperforated appendicitis: defect in enhancing appendiceal wall-
      depiction with multi-detector row CT.
AB  - PURPOSE: To retrospectively evaluate the accuracy of multi-detector row helical
      computed tomography (CT) with intravenous contrast material and without oral
      contrast material for depiction of perforated appendicitis. MATERIALS AND
      METHODS: This study was approved by the institutional review board; informed
      consent was waived. CT images in 102 patients (60 male patients, 42 female
      patients; age range, 4-82 years; mean age, 37.3 years) with surgically and
      pathologically proved appendicitis who were examined between January 2000 and
      December 2002 were retrospectively reviewed. Original transverse sections at 3-
      or 2-mm collimation and 1.5- or 1.0-mm intervals were viewed by using cine mode
      observation. Two independent observers evaluated five specific findings (defect
      in enhancing appendiceal wall, abscess, phlegmon, extraluminal air, and
      extraluminal appendicolith). Sensitivity, specificity, and accuracy of the
      specific findings in the diagnosis of perforated appendicitis were evaluated.
      RESULTS: Perforated appendicitis was present in 40 patients, and nonperforated
      appendicitis was present in 62 patients. A defect in the enhancing appendiceal
      wall was present in 38 patients in the perforated group. Two patients in the
      nonperforated group had false-positive findings for a defect in the enhancing
      appendiceal wall. Sensitivity, specificity, and accuracy of this finding in the
      diagnosis of perforation were 95.0%, 96.8%, and 96.1%, respectively.
      Sensitivities for abscess, extraluminal air, and extraluminal appendicolith were
      37.5%, 22.5%, and 32.5%, respectively. These three findings were not found in
      patients with nonperforated appendicitis. Phlegmon was seen in 16 patients in the
      perforated group and in three patients in the nonperforated group. Sensitivity,
      specificity, and accuracy of phlegmon in the diagnosis of perforation were 40.0%,
      95.2%, and 73.5%, respectively. CONCLUSION: Multi-detector row CT allows an
      accurate (96.1%) diagnosis of appendiceal perforation by the depiction of a
      defect in the contrast material-enhanced appendiceal wall.

PMID- 18096536
TI  - CT colonography with computer-aided detection as a second reader: observer
      performance study.
AB  - PURPOSE: To evaluate the effect of computer-aided detection (CAD) as second
      reader on radiologists' diagnostic performance in interpreting computed
      tomographic (CT) colonographic examinations by using a primary two-dimensional
      (2D) approach, with segmental, unblinded optical colonoscopy as the reference
      standard. MATERIALS AND METHODS: This HIPAA-compliant study was IRB-approved with
      written informed consent. Four board-certified radiologists analyzed 60 CT
      examinations with a commercially available review system. Two-dimensional
      transverse views were used for initial polyp detection, while three-dimensional
      (3D) endoluminal and 2D multiplanar views were available for problem solving.
      After initial review without CAD, the reader was shown CAD-identified polyp
      candidates. The readers were then allowed to add to or modify their original
      diagnoses. Polyp location, CT Colonography Reporting and Data System
      categorization, and reader confidence as to the likelihood of a candidate being a
      polyp were recorded before and after CAD reading. The area under the receiver
      operating characteristic (ROC) curve (AUC), sensitivity, and specificity were
      estimated for CT examinations with and without CAD readings by using multireader
      multicase analysis. RESULTS: Use of CAD led to nonsignificant average reader AUC
      increases of 0.03, 0.03, and 0.04 for patients with adenomatous polyps 6 mm or
      larger, 6-9 mm, and 10 mm or larger, respectively (P > or = .25); likewise, CAD
      increased average reader sensitivity by 0.15, 0.16, and 0.14 for those respective
      groups, with a corresponding decrease in specificity of 0.14. These changes
      achieved significance for the 6 mm or larger group (P < .01), 6-9 mm group (P <
      .02), and for specificity (P < .01), but not for the 10 mm or larger group (P >
      .16). The average reading time was 5.1 minutes +/- 3.4 (standard deviation)
      without CAD. CAD added an average of 3.1 minutes +/- 4.3 (62%) to each reading
      (supine and prone positions combined); average total reading time, 8.2 minutes +/
      5.8. CONCLUSION: Use of CAD led to a significant increase in sensitivity for
      detecting polyps in the 6 mm or larger and 6-9 mm groups at the expense of a
      similar significant reduction in specificity.

PMID- 18096538
TI  - Individual kidney blood flow measured with contrast-enhanced first-pass perfusion
      MR imaging.
AB  - The study design was HIPAA-compliant and approved by the Institutional Review
      Board, with all participants providing signed informed consent prior to the
      study. The purpose of this study was to prospectively evaluate the feasibility of
      determining renal blood flow (RBF) by using a technique based on intravenous
      administration of gadolinium chelate and evaluation of first-pass gadolinium
      chelate perfusion by using highly accelerated three-dimensional (3D) gradient
      echo magnetic resonance (MR) imaging of the kidney in freely breathing subjects.
      Flow is determined with Kety-Schmidt formalism by modeling the uptake of
      gadolinium chelate in the kidney prior to its leaving through the venous system.
      Validation of the gadolinium chelate perfusion technique is based on comparison
      of values determined for participants with phase-contrast gradient-echo imaging.
      The model fit to the measured data is excellent over the first 7-8 seconds of
      gadolinium chelate uptake and diverges after its appearance in the renal vein.
      The perfusion data analysis technique showed less than 10% interobserver
      variation. The average difference between phase-contrast and gadolinium chelate
      perfusion measurements was 0.08 mL/sec (95% confidence interval: -3.73, 3.58) for
      left and right kidneys. This study demonstrates feasibility of the gadolinium
      chelate perfusion method for RBF measurement and discusses potential
      applications. SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/246/1/241/DC1.

PMID- 18096537
TI  - Adaptive postprocessing techniques for myocardial tissue tracking with
      displacement-encoded MR imaging.
AB  - The purpose of this study was to prospectively assess the effects of two adaptive
      postprocessing techniques on the evaluation of myocardial function with
      displacement-encoded magnetic resonance (MR) imaging, including sensitivity for
      abnormal wall motion, with two-dimensional echocardiography as the reference
      standard. Sixteen patients (11 men, five women; age range, 26-74 years) and 12
      volunteers (six men, six women; age range, 29-53 years) underwent breath-hold MR
      imaging. Institutional review board approval and informed consent were obtained.
      Adaptive phase-unwrapping and spatial filtering techniques were compared with
      conventional phase-unwrapping and spatial filtering techniques. Use of the
      adaptive techniques led to a reduced rate of failure with the phase-unwrapping
      technique from 18.9% to 0.6% (P < .001), resulted in lower variability of
      segmental strain measurements among healthy volunteers (P < .001 to P = .02), and
      increased the sensitivity of quantitative detection of abnormal segments in
      patients from 82.5% to 87.7% (P = .034). The adaptive techniques improved the
      semiautomated postprocessing of displacement-encoded cardiac images and increased
      the sensitivity of detection of abnormal wall motion in patients. SUPPLEMENTAL
      MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/246/1/229/DC1.

PMID- 18096539
TI  - Lung cancers missed on chest radiographs: results obtained with a commercial
      computer-aided detection program.
AB  - PURPOSE: To retrospectively determine the sensitivity of and number of false
      positive marks made by a commercially available computer-aided detection (CAD)
      system for identifying lung cancers previously missed on chest radiographs by
      radiologists, with histopathologic results as the reference standard. MATERIALS
      AND METHODS: Institutional review board approval was obtained for this HIPAA
      compliant study; the requirement for informed patient consent was waived. A CAD
      nodule detection program was applied to 34 posteroanterior digital chest
      radiographs obtained in 34 patients (21 men, 13 women; mean age, 69 years). All
      34 radiographs showed a nodular lung cancer that was apparent in retrospect but
      had not been mentioned in the report. Two radiologists identified these
      radiologist-missed cancers on the chest radiographs and graded them for
      visibility, location, subtlety (extremely subtle to extremely obvious on a 10
      point scale), and actionability (actionable or not actionable according to
      whether the radiologists probably would have recommended follow-up if the nodule
      had been detected). The CAD results were analyzed to determine the numbers of
      cancers and false-positive nodules marked and to correlate the CAD results with
      the nodule grades for subtlety and actionability. The chi2 test or Fisher exact
      test for independence was used to compare CAD sensitivity between the very subtle
      (grade 1-3) and relatively obvious (grade > 3) cancers and between the actionable
      and not actionable cancers. RESULTS: The CAD program had an overall sensitivity
      of 35% (12 of 34 cancers), identifying seven (30%) of 23 very subtle and five
      (45%) of 11 relatively obvious radiologist-missed cancers (P = .21) and detecting
      two (25%) of eight missed not actionable and ten (38%) of 26 missed actionable
      cancers (P = .33). The CAD program made an average of 5.9 false-positive marks
      per radiograph. CONCLUSION: The described CAD system can mark a substantial
      proportion of visually subtle lung cancers that are likely to be missed by
      radiologists.

PMID- 18096540
TI  - Interval increase in right-left ventricular diameter ratios at CT as a predictor
      of 30-day mortality after acute pulmonary embolism: initial experience.
AB  - PURPOSE: To retrospectively determine if the interval increase of right
      ventricular-left ventricular (RV/LV) diameter ratio from negative prior to
      positive current computed tomographic (CT) examination findings for pulmonary
      embolism (PE) is more accurate for predicting 30-day mortality than positive CT
      ratio alone, by using patient 30-day mortality as reference standard. MATERIALS
      AND METHODS: This IRB-approved, HIPAA-compliant study had waiver of informed
      consent and retrospectively reviewed 50 patients (19 men, 31 women; mean age, 60
      years) with negative prior and positive current CT findings for acute PE (median
      interval, 63 days). Interval increase was defined as percentage change in RV/LV
      diameter ratio by using reformatted four-chamber views. Receiver operating
      characteristic (ROC) analysis compared the interval increase with the RV/LV
      diameter ratio from the positive findings alone for PE-related and all-cause
      mortality. RESULTS: Twelve (24%) patients died in 30 days; nine were PE-related.
      The interval increase was significantly more accurate overall than the ratio from
      the positive study alone for PE-related (area under the ROC curve [AUC] = 0.95 vs
      0.73, P = .003) and all-cause (AUC = 0.81 vs 0.66, P = .05) mortality. The
      respective sensitivity, specificity, positive predictive value, and negative
      predictive value were 0.78 (seven of nine; 95% confidence interval [CI]: 0.43,
      1.00), 0.93 (38 of 41; 95% CI: 0.83, 1.00), 0.70 (seven of 10; 95% CI: 0.38,
      1.00), and 0.95 (38 of 40; 95% CI: 0.87, 1.00) for PE-related mortality (interval
      increase, >18%) and 0.75 (nine of 12; 95% CI: 0.49, 1.00), 0.89 (34 of 38; 95%
      CI: 0.80, 0.99), 0.69 (nine of 13; 95% CI: 0.44, 0.95), and 0.92 (34 of 37; 95%
      CI: 0.83, 1.00) for all-cause mortality (interval increase, >15%). At target
      sensitivity (0.75), specificity of interval increase was significantly higher
      than from positive scans alone for both PE-related (0.93 vs 0.59, P = .001) and
      all-cause (0.89 vs 0.58, P = .05) mortality. CONCLUSION: The interval increase in
      four-chamber RV/LV diameter ratio is more accurate than the diameter ratio of the
      CT examination with with positive findings for PE alone for mortality prediction
      after acute PE.

PMID- 18096541
TI  - Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary
      fibrosis and nonspecific interstitial pneumonia by using thin-section CT.
AB  - PURPOSE: To retrospectively assess the accuracy of thin-section computed
      tomography (CT) in distinguishing chronic hypersensitivity pneumonitis (HP) from
      idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia
      (NSIP), with histologic results as the reference standard. MATERIALS AND METHODS:
      This retrospective study was approved by the institutional research boards of the
      participating centers, and informed consent was waived. There was HIPAA
      compliance for all U.S. patients. The study included 66 patients (36 men, 30
      women; mean age, 58.8 years +/- 10.9 [standard deviation]) with proved chronic HP
      (n = 18), IPF (n = 23), or NSIP (n = 25) who underwent CT. Two independent
      readers assessed the CT images, made a first-choice diagnosis, and noted the
      degree of confidence in the diagnosis. A general linear model was used to
      identify CT features that independently differentiated chronic HP from IPF and
      NSIP. Weighted kappa statistic was used to assess interobserver agreement.
      RESULTS: The CT features that best differentiated chronic HP were lobular areas
      with decreased attenuation and vascularity, centrilobular nodules, and absence of
      lower zone predominance of abnormalities (P < or = .008). The features that best
      differentiated NSIP were relative subpleural sparing, absence of lobular areas
      with decreased attenuation, and lack of honeycombing (P < or = .002). The
      features that best differentiated IPF were basal predominance of honeycombing,
      absence of relative subpleural sparing, and absence centrilobular nodules (P < or
      = .004). A confident diagnosis was made in 70 (53%) of 132 readings. This
      diagnosis was correct in 66 (94%) of 70 readings. The accuracy for the entire
      cohort was 80%. Interobserver agreement for confident diagnosis was good to
      excellent (kappa = 0.77-0.96). CONCLUSION: Characteristic CT features of chronic
      HP, IPF, and NSIP allow confident distinction between these entities in
      approximately 50% of patients.

PMID- 18096542
TI  - Intravascular US-guided direct intrahepatic portocaval shunt with an expanded
      polytetrafluoroethylene-covered stent-graft.
AB  - PURPOSE: To retrospectively evaluate the midterm patency rate of the nitinol
      (Viatorr, W.L. Gore and Associates, Flagstaff, Ariz) stent-graft for direct
      intrahepatic portacaval shunt (DIPS) creation. MATERIALS AND METHODS:
      Institutional Review Board approval for this retrospective HIPAA-compliant study
      was obtained with waiver of informed consent. DIPS was created in 18 men and one
      woman (median age, 54 years; range, 45-65 years) by using nitinol
      polytetrafluoroethylene (PTFE)-covered stent-grafts. The primary indications were
      intractable ascites (n = 14), acute variceal bleeding (n = 3), and hydrothorax (n
      = 2). Follow-up included Doppler ultrasonography at 1, 6, and 12 months and
      venography with manometry at 6-month intervals after the procedure. Shunt patency
      and cumulative survival were evaluated by using the Kaplan-Meier method and
      survival curves were plotted. Differences in mean portosystemic gradients (PSGs)
      were evaluated by using the Student t test. Multiple regression analysis for
      survival and DIPS patency were performed for the following parameters: Child-Pugh
      class, model of end-stage liver disease score, pre- and post-DIPS PSGs, pre-DIPS
      liver function tests, and pre-DIPS creatinine levels. RESULTS: DIPS creation was
      successful in all patients. Effective portal decompression and free antegrade
      shunt flow was achieved in all patients. Intraperitoneal bleeding occurred in one
      patient during the procedure and was controlled during the same procedure by
      placing a second nitinol stent-graft. The primary patency rate was 100% at all
      times during the follow-up period (range, 2 days to 30 months; mean, 256 days;
      median, 160 days). Flow restrictors were deployed in two (11%) of 19 patients.
      The 1-year mortality rate was 37% (seven of 19). CONCLUSION: Patency after DIPS
      creation with the nitinol PTFE-covered stent-graft was superior to that after
      TIPS with the nitinol stent-graft.

PMID- 18096544
TI  - Case 128: Bilateral ovarian fibromas in nevoid basal cell carcinoma syndrome.

PMID- 18096545
TI  - Case 129: Polyarteritis nodosa.

PMID- 18096546
TI  - The boot-shaped heart sign.

PMID- 18096547
TI  - Declining number of publications by American authors in Radiology.

PMID- 18096548
TI  - Scientific presentations at radiologic meetings, subsequent full-text
      publications, and authors' country of origin.

PMID- 18096549
TI  - Quantifying "overdiagnosis" in lung cancer screening.

PMID- 18096550
TI  - Measurement methods for small pulmonary nodules.

PMID- 18096551
TI  - CT-guided pulmonary radiofrequency ablation.

PMID- 18096552
TI  - Concerns: Choosing a radiology workstation.

PMID- 18096553
TI  - Patlak plot analysis for assessment of single-kidney glomerular filtration rate
      with dynamic CT.

PMID- 18096554
TI  - Multidetector CT of acute gastrointestinal bleeding.

PMID- 18096555
TI  - Physicochemical feature-based classification of amino acid mutations.
AB  - A huge quantity of gene and protein sequences have become available during the
      post-genomic era, and information about genetic variations, including amino acid
      substitutions and SNPs, is accumulating rapidly. To understand the effects of
      these changes, it is often essential to apply bioinformatics tools. Where there
      is a lack of homologous sequences or a three-dimensional structure, it becomes
      essential to predict the effects of mutations based solely on protein sequence
      information. Several computational methods utilizing machine learning techniques
      have been developed. These predictions generally use the 20-alphabet amino acid
      code to train the model. With limited available data, the 20-alphabet amino acid
      features may introduce so many parameters that the model becomes over-fitted. To
      decrease the number of parameters, we propose a physicochemical feature-based
      method to forecast the effects of amino acid substitutions on protein stability.
      Protein structure alterations caused by mutations can be classified as
      stabilizing or destabilizing. Based on experimental folding-unfolding free energy
      (DeltaDeltaG) values, we trained a support vector machine with a cleaned data
      set. The physicochemical properties of the mutated residues, the number of
      neighboring residues in the primary sequence and the temperature and pH were used
      as input attributes. Different kernel functions, attributes and window sizes were
      optimized. An average accuracy of 80% was obtained in cross-validation
      experiments.

PMID- 18096556
TI  - In vitro activity of ceftobiprole against Burkholderia pseudomallei.

PMID- 18096557
TI  - Pharmacokinetics and biodistribution of amikacin encapsulated in carrier
      erythrocytes.
AB  - OBJECTIVES: To study the changes in the pharmacokinetics and tissue distribution
      of the aminoglycoside amikacin in rats using amikacin carrier erythrocytes as a
      delivery system. METHODS: Amikacin-loaded erythrocytes were obtained using a
      hypotonic dialysis method. The pharmacokinetic and tissue distribution of
      amikacin were studied in three groups of rats receiving intravenous amikacin in
      saline solution, amikacin-loaded erythrocytes and amikacin-loaded erythrocytes
      treated with glutaraldehyde. Pharmacokinetic analysis was accomplished using
      model-independent methods. RESULTS: Administration of the antibiotic using
      carrier erythrocytes elicited a sustained release effect, with an increase in the
      plasma half-life and in the area under the curve of the antibiotic. The tissue
      pharmacokinetics of amikacin using carrier erythrocytes in comparison with a
      control group revealed an accumulation of the antibiotic in specific tissues such
      as the liver and spleen, a similar pharmacokinetics in the lung and moderate
      changes in the pharmacokinetics in the kidney. Studies of tissue concentrations
      after the injection of glutaraldehyde-treated loaded erythrocytes demonstrated
      important changes in organs of the reticulo-endothelial system (RES) in
      comparison with the results observed for standard carrier erythrocytes, higher
      levels being observed in the liver whereas spleen levels decreased. CONCLUSIONS:
      The administration of amikacin in loaded erythrocytes in rats leads to
      significant changes in the pharmacokinetic behaviour of the antibiotic, a greater
      accumulation being observed in RES organs such as liver and spleen. This shows
      that loaded erythrocytes are potentially useful for the delivery of antibiotics
      in phagocytic cells located in the RES.

PMID- 18096559
TI  - Methicillin-resistant Staphylococcus aureus and Staphylococcus pseudintermedius
      detected in the BfT-GermVet monitoring programme 2004-2006 in Germany.
AB  - OBJECTIVES: During recent years, methicillin-resistant Staphylococcus aureus
      (MRSA) strains from animals have become the focus of various studies. In the
      present study, coagulase-positive staphylococci obtained from pigs, dogs and cats
      suffering from acute infections, which had been collected in the BfT-GermVet
      monitoring programme in Germany and phenotypically identified as oxacillin
      resistant, were characterized. METHODS: The staphylococci were comparatively
      investigated for their resistance phenotypes and genotypes. Resistance genes were
      identified by PCR. MRSA strains were further characterized by SmaI
      macrorestriction analysis and spa typing to assess their genomic relationships.
      RESULTS: Among the 248 strains tested, 7 strains (5 porcine S. aureus and 2
      canine Staphylococcus pseudintermedius) carried the resistance gene mecA.
      Gentamicin resistance was based on the presence of the gene aacA/aphD while three
      different tetracycline resistance genes, tet(K), tet(L) and tet(M), alone or in
      combinations, were detected. The single macrolide/lincosamide-resistant strain
      carried an erm(A) gene. All MRSA strains proved to be non-typeable by SmaI
      macrorestriction analysis and exhibited the spa types t011 (four strains) or t034
      (one strain). CONCLUSIONS: Based on their spa types and their non-respondence to
      SmaI digestion, all five porcine MRSA strains resembled MRSA strains of
      multilocus sequence type ST398, previously detected among pigs in neighbouring
      countries such as The Netherlands or Denmark. The results of this study indicate
      that such strains are also involved in defined disease conditions of pigs from
      various parts of Germany.

PMID- 18096560
TI  - Effect of rifampicin-based antitubercular therapy on nevirapine plasma
      concentrations in South African adults with HIV-associated tuberculosis.
AB  - BACKGROUND AND OBJECTIVES: Nevirapine-containing antiretroviral therapy (ART) and
      rifampicin-based antitubercular therapy are commonly co-administered in Africa,
      where nevirapine is often the only available non-nucleoside reverse transcriptase
      inhibitor. Rifampicin induces the metabolism of nevirapine, but the extent of the
      reduction in nevirapine concentrations has varied widely in previous studies. We
      describe the steady-state pharmacokinetics of nevirapine during and after
      antitubercular therapy in South African patients. METHODS: Sixteen patients
      receiving ART including standard doses of nevirapine were admitted twice for
      intensive pharmacokinetic sampling: during and after rifampicin-based
      antitubercular therapy. RESULTS: Geometric mean ratios for nevirapine
      pharmacokinetic parameters during versus after antitubercular therapy were 0.61
      [90% confidence interval (CI) 0.49-0.79] for Cmax, 0.64 (90% CI 0.52-0.80) for
      area under the curve up to 12 h (AUC(0-12)) and 0.68 (90% CI 0.53-0.86) for Cmin.
      Nevirapine Cmin was subtherapeutic (<3 mg/L) in six patients during
      antitubercular therapy (one of whom developed virological failure) and in none
      afterwards. There was no correlation between rifampicin concentrations and the
      degree of nevirapine induction assessed by the proportional change in nevirapine
      concentrations between the two admissions. The ratio of nevirapine AUC(0-12) to
      the AUC(0-12) of its 12-hydroxy metabolite was significantly lower in the
      presence of antitubercular therapy, consistent with induced metabolism.
      CONCLUSIONS: Nevirapine concentrations were significantly decreased by
      concomitant rifampicin-based antitubercular therapy and a high proportion of
      patients had subtherapeutic plasma concentrations. Further study in African
      patients is required to determine the implications for treatment outcomes.

PMID- 18096561
TI  - Evidence of temporal cortical dysfunction in rhesus monkeys following chronic
      cocaine self-administration.
AB  - Cocaine abusers show impaired performance on cognitive tasks that engage
      prefrontal cortex. These deficits may contribute to impaired control and relapse
      in abusers. Understanding the neuronal substrates that lead to these deficits
      requires animal models that are relevant to the human condition. However, to
      date, models have mostly focused on behaviors mediated by subcortical systems.
      Here we evaluated the impact of long-term self-administration of cocaine in the
      rhesus monkey on cognitive performance. Tests included stimulus discrimination
      (SD)/reversal and delayed alternation tasks. The chronic cocaine animals showed
      marked deficits in ability to organize their behavior for maximal reward. This
      was demonstrated by an increased time needed to acquire SDs. Deficits were also
      indicated by an increased time to initially learn the delayed alternation task,
      and to adapt strategies for bypassing a reliance on working memory to respond
      accurately. Working memory per se (delay dependent performance) was not affected
      by chronic self-administration. This pattern of cognitive deficits suggests
      dysfunction that extends beyond localized prefrontal cortical areas. In
      particular, it appears that temporal cortical function is also compromised. This
      agrees with other recent clinical and preclinical findings, and suggests further
      study into addiction related dysfunction across more widespread cortical networks
      is warranted.

PMID- 18096563
TI  - Endometriosis and human infertility: a new investigation into the role of eutopic
      endometrium.
AB  - BACKGROUND: Endometriosis is related to infertility even in the absence of
      mechanical alterations of the reproductive tract. Even though the pathogenesis of
      this phenomenon is still unclear, an impaired endometrial receptivity has been
      recently suggested. The aim of the present study was to investigate if
      endometriotic peritoneal fluids (EPF) could interfere with endometrial stromal
      cell (ESC) decidualization and if tumor necrosis factor (TNF)-alpha could be
      involved in the EPF effect. METHODS: Eutopic ESC were isolated from patients with
      or without endometriosis. ESC were treated with 17beta-estradiol 10(-8) M and
      6alpha-methyl-17alpha-hydroxyprogesteroneacetate 2x10(-7) M for 16 days. In vitro
      decidualization was morphologically and biochemically assessed. We analysed
      whether ESC decidualization could be affected by EPF or peritoneal fluids from
      control patients (CPF), with or without soluble TNF-alpha receptor 1 (sTNFR-1).
      RESULTS: Compared with ESC from control patients, eutopic ESC from patients with
      endometriosis showed an impaired decidualization. Decidualization of normal ESC
      was morphologically normal but biochemically abnormal in the presence of EPF,
      which was able to decrease the secretion of decidualization markers. sTNFR-1 was
      able to partially counteract this effect. CONCLUSIONS: In endometriosis, the
      milieu surrounding the uterine cavity may be involved in impaired eutopic ESC
      decidualization, partially due to increased peritoneal levels of TNF-alpha.

PMID- 18096562
TI  - Functional phenotype of macrophages depends on assay procedures.
AB  - Macrophages display different phenotypes that can switch in response to their
      micro-environment. In our earlier study (Chiang, C. S., Liu, W. C. and Jung, S.
      M., 2005. Compartmental responses after thoracic irradiation of mice: strain
      differences. Int. J. Radiat. Oncol. Biol. Phys. 62:862) on radiation-induced
      cytokine expression in lung lavage samples, there was a suggestion that the
      procedures used to harvest lung macrophages affected the profiles they expressed.
      To further explore this issue, we examined gene expression by cell populations,
      mainly macrophages, isolated by lavage from lung and peritoneal cavity following
      either in vivo or in vitro stimulation with LPS, IFN-gamma or irradiation. We
      found that expression of mRNA for tumor necrosis factor-alpha, IL-1 alpha/beta
      and IL-6 varied several fold depending on whether the assay was performed on
      cells immediately after isolation or after in vitro manipulation. The relative
      level of inducible nitric oxide synthase (iNOS) to arginase I (Arg I), which is
      frequently used as index of the M1 versus M2 functional macrophage phenotype,
      also varied. LPS stimulation in vivo was able to change the profile from Arg I
      expression to one where the iNOS pathway became dominant, but was unable to do
      this in vitro. This contrasts with the ability of IFN-gamma to generate an iNOS
      dominant pathway in vitro, but not in vivo. This study cautions that the
      expression of inflammatory cytokines and the iNOS to Arg I ratio, which is often
      used as an index of their functional capacity, varies with the experimental
      conditions.

PMID- 18096564
TI  - Mammalian nonsynonymous sites are not overdispersed: comparative genomic analysis
      of index of dispersion of mammalian proteins.
AB  - It is often stated that patterns of nonsynonymous rate variation among mammalian
      lineages are more irregular than expected or overdispersed under the neutral
      model, whereas synonymous sites conform to the neutral model. Here we reexamined
      genome-wide patterns of the variance to mean ratio, or index of dispersion (R),
      of substitutions in proteins from human, mouse, and dog. Contrary to the
      prevailing notion, we found that the mean index of dispersion for nonsynonymous
      sites of mammalian proteins is not significantly different from 1. We propose
      that earlier analyses were biased because the data included disproportionately
      more protein hormones, which tend to be more dispersed than genes in other
      functional categories. Synonymous sites exhibit greater degree of dispersion than
      nonsynonymous sites, although similar to earlier estimates and potentially due to
      errors associated with correction for multiple hits. Overall, our analysis
      identifies strong genome-wide generation-time effect and natural selection as
      important determinants of among-lineage variation of protein evolutionary rates.
      Furthermore, patterns of lineage-specific selective constraint are consistent
      with the nearly neutral model of molecular evolution.

PMID- 18096565
TI  - Multicenter phase II trial of gefitinib first-line therapy followed by
      chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03.
AB  - BACKGROUND: Gefitinib is active in patients with pretreated non-small-cell lung
      cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line
      treatment in advanced NSCLC followed by chemotherapy at disease progression.
      PATIENTS AND METHODS: In all, 63 patients with chemotherapy-naive stage IIIB/IV
      NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was
      replaced by cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1,
      8 for up to six 3-week cycles. Primary end point was the disease stabilization
      rate (DSR) after 12 weeks of gefitinib. RESULTS: After 12 weeks of gefitinib, the
      DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP)
      was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n =
      9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal
      growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS
      was not reached after the follow-up of 21.6 months. In all, 41 patients received
      chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months.
      CONCLUSIONS: First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in
      an unselected patients population. Never smokers and patients with EGFR mutations
      tend to have a better outcome; hence, further trials in selected patients are
      warranted.

PMID- 18096566
TI  - The impact of a false-positive MRI on the choice for mastectomy in BRCA mutation
      carriers is limited.
AB  - PURPOSE: To assess the false-positive rate of breast cancer surveillance by
      magnetic resonance imaging (MRI) in BRCA mutation carriers and the impact of an
      abnormal mammography or breast MRI on the patients' decision for prophylactic
      mastectomy. PATIENTS AND METHODS: A total of 196 BRCA mutation carriers were
      included with a median follow-up of 2 years (range 1-9) with annual mammography
      and MRI. Preference for prophylactic mastectomy was registered at first
      surveillance after the mutation carriership was revealed. RESULTS: In all, 41%
      (81 of 196) of the women had at least one positive MRI or mammography. Malignancy
      was detected in 17 women: 11 at surveillance, 4 at an intended prophylactic
      mastectomy and 2 had an interval cancer. Imaging by mammography and MRI had a
      sensitivity of 71% and a specificity of 90%. The probability that a positive MRI
      result is false positive was 83%. In the group with a prior preference for
      mastectomy with and without a false-positive imaging, prophylactic mastectomy was
      carried out in 89% and 66%, respectively (P = 0.06), in the group with prior
      preference for surveillance these percentages were 15% and 11%, respectively (P =
      0.47). CONCLUSION: Although the rate of false-positive MRI results is high, the
      impact on the choice for prophylactic mastectomy is limited and is determined by
      the woman's preference before the establishment of a BRCA mutation.

PMID- 18096567
TI  - Autologous stem-cell transplantation as consolidation therapy for diffuse large B
      cell lymphoma patients with overexpression of bcl-2 protein. Results of the
      Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial LNH98-B2.
AB  - BACKGROUND: Overexpression of B-cell lymphoma 2 (bcl-2) protein is a simple
      biological adverse prognostic factor that could delimit the poor prognosis
      population candidate for improvement with high-dose therapy and autologous stem
      cell transplantation (ASCT) in diffuse large B-cell lymphoma (DLBCL). Therefore,
      we conducted a risk-adapted phase II study with ASCT as consolidation therapy in
      low-intermediate risk (LIR) International Prognostic Index patients aged < or =
      60 years with bcl-2 overexpression (bcl-2+). PATIENTS AND METHODS: Induction
      chemotherapy consisted of four courses of adriamycin, cyclophosphamide,
      vindesine, bleomycin, prednisone, once every 2 weeks. Responding bcl-2+ patients
      received ASCT as consolidation, and those without bcl-2 overexpression (bcl-2-)
      conventional chemotherapy. Three hundred and sixteen LIR patients with DLBCL,
      aged between 18 and 60 years, were included. Of these, 177 (56%) were bcl-2+ and
      139 (44%) bcl-2-. RESULTS: Complete response rates after induction chemotherapy
      were similar in bcl-2+ and bcl-2- patients (74% versus 78%). Estimated 2-year
      event-free survival and disease-free survival for the bcl-2+ subgroup were 79%
      and 87%, for bcl-2- 84% and 92% and for the whole series 81% and 90%,
      respectively. CONCLUSIONS: These results demonstrate that taking into account
      biological characteristics in prospective multicenter trials allow successful
      adjustment of treatment and indicate that ASCT may counteract the adverse
      prognostic value of bcl-2 overexpression in responding LIR patients.

PMID- 18096568
TI  - New oral anticoagulants in atrial fibrillation.
AB  - Atrial fibrillation (AF) is a major risk factor for stroke. Currently,
      acetylsalicylic acid (a platelet inhibitor) and vitamin K antagonists (VKAs; oral
      anticoagulants), including warfarin, are the only approved antithrombotic
      therapies for stroke prevention in patients with AF. Although effective, VKAs
      have unpredictable pharmacological effects, requiring regular coagulation
      monitoring and dose adjustment to maintain effects within the therapeutic range.
      The clinical development pathway for novel anticoagulants often involves
      evaluation of efficacy and safety in a short-term indication, such as the
      prevention of venous thrombo-embolism (VTE), followed by longer-term VTE
      treatment studies, and finally chronic indications, including stroke prevention
      studies in patients with AF. The coagulation pathway provides many targets for
      novel anticoagulants, including Factor Xa (FXa) and Factor IIa (thrombin).
      Numerous oral, direct FXa inhibitors are in various stages of clinical
      development, including rivaroxaban, LY517717, YM150, DU-176b, apixaban, and
      betrixaban, and are anticipated to overcome the limitations of VKAs. Dabigatran
      is the only oral direct thrombin inhibitor in late-stage development. Studies of
      these agents for stroke prevention in patients with AF are planned or ongoing. If
      approved, they may represent the next generation of anticoagulants, by providing
      new therapeutic options for stroke prevention in patients with AF.

PMID- 18096569
TI  - Aortic elasticity and size in bicuspid aortic valve syndrome.
AB  - AIMS: To investigate the relation between aortic elastic properties and size in
      bicuspid aortic valves (BAVs). METHODS AND RESULTS: 127 BAV outpatients (121
      males; age 23 +/- 10 years) with no or mild valvular impairment, were recruited
      with 114 control subjects comparable for age, gender, and body size. Aortic
      distensibility (DIS) and stiffness index (SI) were derived by M-mode evaluation
      of the aortic root together with blood pressure measured by cuff
      sphygmomanometer. BAVs vs. controls had increased aortic diameter (P < 0.0001),
      higher systolic (P = 0.02) and pulse (P = 0.04) pressures. DIS was lower in BAVs
      than in controls (4.71 +/- 3.67 vs. 7.44 +/- 3.94 10(-6) cm(2)dyne(-1),
      respectively; P < 0.0001) and SI was greater in BAVs (7.21 +/- 4.93 vs. 3.57 +/-
      1.88, respectively; P < 0.0001). Definite impairment in aortic elasticity was
      present in 53 (42%) BAVs. Both DIS and SI were related (P < 0.0001) to aortic
      size in BAVs and controls. After adjusting for aortic size and blood pressure,
      the regression relations between SI and aortic diameter of BAVs were
      significantly different from controls (P = 0.0052). CONCLUSION: Abnormal aortic
      elasticity is a common finding in BAVs with no or mild aortic valve impairment.
      However, impaired aortic stiffness is not due to aortic dilation. Simple
      assessment of aortic size may thus fail to identify early abnormal load bearing
      characteristics of the aortic wall in BAVs.

PMID- 18096570
TI  - Gestational and lactational exposure to ethinyl estradiol, but not bisphenol A,
      decreases androgen-dependent reproductive organ weights and epididymal sperm
      abundance in the male long evans hooded rat.
AB  - Many chemicals released into the environment are capable of disrupting normal sex
      steroid balance, including the oral contraceptive ethinyl estradiol (EE) and the
      plastic monomer bisphenol A (BPA). EE and BPA are reported to impair reproductive
      organ development in laboratory animals; however, effects of lower doses of these
      chemicals have been debated. The goal of the current study was to determine
      whether relatively low oral doses of EE or BPA would alter male reproductive
      morphology and associated hormone levels of Long Evans hooded rat. Dams were
      gavaged with corn oil vehicle, EE (0.05-50 mug/kg/day) or BPA (2, 20, and 200
      mug/kg/day) during pregnancy through lactation from gestational day 7 to
      postnatal day (PND) 18. Anogenital distance was measured at PND2 and nipple
      retention was measured at PND14 in male pups. Male offspring were euthanized
      beginning at PND150, and sera and organs were collected for analyses. Adult body
      weight was significantly decreased in males exposed to 50 mug EE/kg/day.
      Developmental EE exposure reduced androgen-dependent tissue weights in a dose
      dependent fashion; for example, seminal vesicle and paired testes weights were
      reduced with >/= 5 mug EE/kg/day. Epididymal sperm counts were also significantly
      decreased with 50 mug EE/kg/day. In contrast, treatment with 2, 20, or 200 mug
      BPA/kg/day or EE at 0.05-1.5 mug/kg/day did not significantly affect any male
      endpoint in the current study. These results demonstrate that developmental
      exposure to oral micromolar doses of EE can permanently disrupt the reproductive
      tract of the male rat.

PMID- 18096571
TI  - Mdm2 as a sensitive and mechanistically informative marker for genotoxicity
      induced by benzo[a]pyrene and dibenzo[a,l]pyrene.
AB  - Mdm2 is an oncoprotein interacting with p53 and maintaining low p53 levels in
      unstressed cells. Here we investigated the effect of genotoxic compounds on Mdm2
      phosphorylation levels. Employing the Mdm2 2A10 antibody and phosphatase
      treatment we found that Mdm2 accumulated in HepG2 cells when exposed to low
      concentrations of genotoxic compounds such as mitomycin C, etoposide, 5
      fluorouracil, and benzo[a]pyrene (BP). The low-dose responses were not
      accompanied by p53 accumulation and the effect of low concentrations of BP on
      Mdm2 was not affected by small interfering RNA for p53. In human lymphoblasts
      10nM BP induced an Mdm2 response. Low concentrations of BP also induced binding
      of Mdm2 to chromatin in HepG2 cells, but no p53 binding or H2AX phosphorylation.
      The more mutagenic dibenzo[a,l]pyrene as well as higher BP concentrations instead
      induced gammaH2AX and p53 Ser15 association with chromatin. Acrolein potentiated
      the effect of BP on p53 stabilization and chromatin binding. Taken together,
      these data suggest that (1) Mdm2 is a sensitive biomarker for certain types of
      genotoxicity, and (2) that polycyclic aromatic hydrocarbons-induced Mdm2 binding
      to chromatin reflects repairable damage, whereas chromatin binding of p53 Ser15
      and gammaH2AX indicates more persistent DNA damage. The analysis of Mdm2 and
      related endpoints might be useful for evaluating mutagenic potentials of DNA
      damages. It is suggested that patterns documented here can be used for separating
      BP doses that induce readily repaired DNA adducts from doses that overwhelm this
      capacity.

PMID- 18096572
TI  - Analysis of Ah receptor-ARNT and Ah receptor-ARNT2 complexes in vitro and in cell
      culture.
AB  - ARNT and ARNT2 proteins are expressed in mammalian and aquatic species and
      exhibit a high level of amino acid identity in the basic-helix loop-helix
      PER/ARNT/SIM domains involved in protein interactions and DNA binding. Since the
      analysis of ARNT2 function at the protein level has been limited, ARNT2 function
      in aryl hydrocarbon receptor (AHR)-mediated signaling was evaluated and compared
      to ARNT. In vitro, ARNT and ARNT2 dimerized equally with the AHR in the presence
      of 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) and ARNT2 outcompeted ARNT for
      binding to the AHR when expressed in excess. In contrast, activation of the AHR
      with 3-methylcholanthrene or benzo[a]pyrene resulted in predominant formation of
      AHR*ARNT complexes. ARNT2 expressed in Hepa-1 cell culture lines with reduced
      ARNT protein resulted in minimal induction of endogenous CYP1A1 protein compared
      to cells expressing ARNT, and mutation of the putative proline residue at amino
      acid 352 to histidine failed to produce an ARNT2 that could function in AHR
      mediated signaling. However, the expression of ARNT2 in wild-type Hepa-1 cells
      reduced TCDD-mediated induction of endogenous CYP1A1 protein by 30%, even though
      AHR*ARNT2 complexes could not be detected in nuclear extracts. Western blot
      analysis of numerous mouse tissues and various cell culture lines showed that
      both endogenous ARNT and ARNT2 could be detected in cells derived from kidney,
      central nervous system, and retinal epithelium. Thus, ARNT2 has the ability to
      dimerize with the liganded AHR in vitro and is influenced by the activating
      ligand yet appears to be limited in its ability to influence AHR-mediated
      signaling in cell culture.

PMID- 18096573
TI  - Lys184 deletion in troponin I impairs relaxation kinetics and induces
      hypercontractility in murine cardiac myofibrils.
AB  - AIMS: To understand the functional consequences of the Lys184 deletion in murine
      cardiac troponin I (mcTnI(DeltaK184)), we have studied the primary effects of
      this mutation linked to familial hypertrophic cardiomyopathy (FHC) at the
      sarcomeric level. METHODS AND RESULTS: Ca(2+) sensitivity and kinetics of force
      development and relaxation were investigated in cardiac myofibrils from
      transgenic mice expressing mcTnI(DeltaK184), as a model which co-segregates with
      FHC. Ca(2+)-dependent conformational changes (switch-on/off) of the fluorescence
      labelled human troponin complex, containing either wild-type hcTnI or mutant
      hcTnI(DeltaK183), were investigated in myofibrils prepared from the guinea pig
      left ventricle. Ca(2+) sensitivity and maximum Ca(2+)-activated and passive
      forces were significantly enhanced and cooperativity was reduced in mutant
      myofibrils. At partial Ca(2+) activation, mutant but not wild-type myofibrils
      displayed spontaneous oscillatory contraction of sarcomeres. Both conformational
      switch-off rates of the incorporated troponin complex and the myofibrillar
      relaxation kinetics were slowed down by the mutation. Impaired relaxation
      kinetics and increased force at low [Ca(2+)] were reversed by 2,3-butanedione
      monoxime (BDM), which traps cross-bridges in non-force-generating states.
      CONCLUSION: We conclude that these changes are not due to alterations of the
      intrinsic cross-bridge kinetics. The molecular mechanism of sarcomeric diastolic
      dysfunction in this FHC model is based on the impaired regulatory switch-off
      kinetics of cTnI, which induces incomplete inhibition of force-generating cross
      bridges at low [Ca(2+)] and thereby slows down relaxation of sarcomeres. Ca(2+)
      sensitization and impairment of the relaxation of sarcomeres induced by this
      mutation may underlie the enhanced systolic function and diastolic dysfunction at
      the sarcomeric level.

PMID- 18096574
TI  - Remote vs. ischaemic preconditioning: the differential role of mitogen-activated
      protein kinase pathways.
AB  - AIMS: Since mitogen-activated protein kinases (MAPKs) were found to be implicated
      in the signalling of ischaemic preconditioning (IPC), we tested the hypothesis of
      a contribution of these protein kinases to remote preconditioning (RPC). METHODS
      AND RESULTS: To determine the role of p38, ERK1/2, and JNK1/2 MAPKs in mediating
      cardiac protection, an in vivo model of myocardial infarction was applied in male
      Wistar rats. RPC or IPC was induced by occlusion of the superior mesenteric
      artery or the left coronary artery, respectively. Infarct size (IS) was
      determined based on 2,3,5-triphenyltetrazolium chloride staining. Phosphorylation
      of the various MAPKs was analysed by immunoblotting in samples of the small
      intestine and myocardium obtained after IPC or RPC procedures. The MAPK
      inhibitors SB203580 (p38), PD98059 (ERK1/2), and SP600125 (JNK1/2) were
      administered to assess the potential significance of MAPK signalling in RPC. Both
      preconditioning stimuli decreased myocardial IS significantly after a lethal
      period of ischaemia. Each of the applied MAPK inhibitors was capable of
      abrogating the RPC-induced cardioprotection. Western blot analysis of myocardial
      samples revealed an increase in phosphorylated amounts of ERK1/2 and JNK1 after
      IPC, whereas phosphorylation of p38 protein was decreased significantly.
      Likewise, RPC resulted in a considerable increase in phosphorylation of ERK1/2
      and JNK1/2 proteins in the small intestine, whereas it did not alter the MAPK
      phosphorylation state in the myocardium. CONCLUSION: All investigated MAPK
      pathways appear to be involved in RPC-induced cardioprotection; however, they do
      not contribute to the alterations that define the preconditioned state of the
      myocardium prior to the infarction.

PMID- 18096576
TI  - Ethics education and academic misconduct.

PMID- 18096577
TI  - Using anonymized reflection to teach ethics: a pilot study.
AB  - Anonymized reflection was employed as an innovative way of teaching ethics in
      order to enhance students' ability in ethical decision making during a Care of
      the Dying Patient and Family' module. Both qualitative and quantitative data were
      collected from the first two student cohorts who experienced anonymized
      reflection ( n = 24). The themes identified were the richness and relevance of
      scenarios, small-group work and a team approach to teaching. Students indicated
      that they preferred this style of teaching. This finding was verified by a postal
      questionnaire conducted four months later. The conclusions drawn from this study
      suggest that using anonymized reflection is an effective method for teaching
      ethics to nurses and indicates that learning about ethical issues in this way
      reduces uncertainties.

PMID- 18096578
TI  - Towards a viable and just global nursing ethics.
AB  - Globalization, an outgrowth of technology, while informing us about people
      throughout the world, also raises our awareness of the extreme economic and
      social disparities that exist among nations. As part of a global discipline,
      nurses are vitally interested in reducing and eliminating disparities so that
      better health is achieved for all people. Recent literature in nursing encourages
      our discipline to engage more actively with social justice issues. Justice in
      health care is a major commitment of nursing; thus questions in the larger sphere
      of globalization, justice and ethics, are our discipline's questions also. Global
      justice, or fairness, is not an issue for some groups or institutions, but a
      deeper human rights issue that is a responsibility for everyone. What can we do
      to help reduce or eliminate the social and economic disparities that are so
      evident? What kind of ethical milieu is needed to address the threat that
      globalization imposes on justice and fairness? This article enriches the
      conceptualization of globalization by investigating recent work by Schweiker and
      Twiss. In addition, I discuss five qualities or characteristics that will
      facilitate the development of a viable and just global ethic. A global ethic
      guides all people in their response to human rights and poverty. Technology and
      business, two major forces in globalization that are generally considered
      beneficial, are critiqued as barriers to social justice and the common good.

PMID- 18096579
TI  - Nursing management of medication errors.
AB  - Medication error is the most common and consistent type of error occurring in
      hospitals. This article attempts to explore the ethical issues relating to the
      nursing management of medication errors in clinical areas in Macau, China. A
      qualitative approach was adopted. Seven registered nurses who were involved in
      medication errors were recruited for in-depth interviews. The interviews were
      transcribed and analyzed using content analysis. Regarding the management of
      patients, the nurses acknowledged the mistakes but did not disclose the incidents
      to patients and relatives. Concerning management of the nurses involved by senior
      staff, most participants experienced fairness, comfort and understanding during
      the process of reporting and investigation. The ethical issues relating to the
      incidents were discussed, particularly in the Chinese context. There is a need
      for further study relating to the disclosure of medication incidents to patients
      and some suggestions were made.

PMID- 18096580
TI  - Ethical challenges for school nurses in documenting schoolchildren's health.
AB  - This study explored Swedish school nurses' experiences of school health record
      documentation. Fifty per cent of a representative sample of Swedish school nurses
      (n = 129) reported difficulties with documenting mental and social health
      problems in family relationships, schoolchildren's behaviour, and school
      situations. Ethical considerations concerning fears of misinterpretation and
      practical barriers to documentation were expressed as reasons for their worries.
      Mental and social ill health is an increasing and often dominating problem among
      schoolchildren, thus proper documentation is a basic issue, both for individuals
      and for the population as a whole. School nurses obviously need professional
      guidance regarding documentation and ethical challenges. Systematic effort should
      be directed towards recognition and support of these nurses' unique opportunities
      to consider, follow and promote all aspects of schoolchildren's health.

PMID- 18096581
TI  - Culture and communication in ethically appropriate care.
AB  - This article considers the difficulties with using Gillon's model for health care
      ethics in the context of clinical practice. Everyday difficulties can arise when
      caring for people from different ethnic and cultural backgrounds, especially when
      they speak little or no English. A case is presented that establishes, owing to
      language and cultural barriers, that midwives may have difficulty in providing
      ethically appropriate care to women of Pakistani Muslim origin in the UK. The use
      of interpreters is discussed; however, there are limitations and counter
      arguments to their use. Training is identified as needed to prepare service
      providers and midwives for meeting the needs of a culturally diverse maternity
      population.

PMID- 18096582
TI  - Uncovering the ethics of suffering using a narrative approach.
AB  - The purpose of this article is to portray the ethics of suffering based on the
      published literature. Narrative use has become common in the fields of nursing
      education and curriculum development and in the determination of practice
      competencies. Understanding the ethics of suffering implies a hermeneutic
      movement between alienation and dedication. To understand the ethical
      significance of human suffering, the scene of suffering is described through the
      concepts of: to endure, to struggle, to sacrifice life and health, and to become.
      To respond, to discover, to approach, to touch and to shape patients' different
      patterns of life implies responsibility: to see, to affirm their dignity by
      being, and to express this in ethical words. Narration plays a crucial role in
      transforming suffering, that is, reformulating patients' stories. It is vital
      that educators should create a learning environment where students can find the
      courage and intention to be present and listen to patients' narratives.

PMID- 18096583
TI  - Older Korean people's desire to participate in health care decision making.
AB  - The purpose of this study was to identify how older Korean people seek
      information and their desire to participate in decision making about their health
      care. A total of 165 elderly people living in Seoul, South Korea, participated in
      the study. Data were collected during individual interviews using the Autonomy
      Preference Index. The mean information-seeking score was high. The mean score for
      their desire to participate with a physician in decision making was lower, but
      this was higher when family members were involved. The study indicates that many
      older people want to receive information about their health care. Families (or
      guardians), as well as older people themselves, should be included in the
      decision-making process. Nurses can encourage older people to express their
      wishes, while treating each individual with respect.

PMID- 18096584
TI  - Supporting sexual activity in long-term care.
AB  - Although nurses in almost every long-term care facility face daily challenges
      involving issues related to residents' sexual lives, guidelines for ethically
      supporting sexual activity are rare and inadequate. A decision-making framework
      was developed to guide care providers in responding to the sexual expression of
      residents in long-term care. The framework recommends that nurses should weigh
      the documented substantial benefits of having a sexual life against harm to the
      resident and others, and against offence to others. This article illustrates the
      use of this ethical decision-making framework by using the example of nurses
      supporting a resident's expression of his sexuality. It is suggested that nurses
      use this framework to guide their practice when related ethical issues arise.

PMID- 18096585
TI  - Three nursing home residents speak about meaning at the end of life.
AB  - This article provides a deeper understanding of how meaning can be created in
      everyday life at a nursing home. It is based on a primary study concerning
      dignity involving 12 older people living in two nursing homes in Sweden. A
      secondary analysis was carried out on data obtained from three of the primary
      participants interviewed over a period of time (18-24 months), with a total of 12
      interviews carried out using an inductive hermeneutic approach. The study reveals
      that sources of meaning were created by having a sense of: physical capability,
      cognitive capability, being needed, and belonging. Meaning was created through
      inner dialogue, communication and relationships with others. A second finding is
      that the experience of meaning can sometimes be hard to realize.

PMID- 18096586
TI  - Nurses' and doctors' perspectives on slow codes.
AB  - The aim of this study was to ascertain nurses' and doctors' perspectives on the
      practice of slow codes, which are cardiopulmonary resuscitative efforts that are
      intentionally performed too slowly for resuscitation to occur. A Heideggerian
      phenomenological study was conducted in 2005, during which data were gathered in
      the Republic of Ireland from three nurses and two doctors (via unstructured
      interviews) and analysed using Colaizzi's reductive procedure. Slow codes do
      occur in Ireland and are intended as beneficent acts. However, slow codes were
      identified as pointless and undignified when intrusive measures were employed.
      There is a need for discussion on the topic of slow codes in Ireland, and for
      aids to cardiopulmonary resuscitation decision making to be developed, such as
      advance directives, communication training, clinical guidelines and an
      explanatory leaflet for patients and families.

PMID- 18096587
TI  - Patient satisfaction versus quality.

PMID- 18096588
TI  - Paediatric nurses' ethical and relational skills.

PMID- 18096589
TI  - Is ethics a necessity or an obligation?

PMID- 18096590
TI  - Measuring effectiveness in community randomized trials of HIV prevention.
AB  - BACKGROUND: Complicated HIV transmission dynamics make it unclear how to design
      and interpret results from community-randomized controlled trials (CRCT) of
      interventions to prevent infection. METHODS: Mathematical modelling was used to
      investigate the effectiveness of interventions to prevent HIV transmission aimed
      at high-risk groups and factors related to the chance of recording a
      statistically significant result. RESULTS: Behaviour change by high-risk groups
      can substantially reduce HIV incidence in the whole population, although its
      effect is sensitive to the structure of the sexual network and the phase of the
      epidemic. There is a delay between the behaviour change happening and its full
      effect being realized in the low-risk group and this can pull the measured
      incidence rate ratio towards one and reduce the chance of recording a
      statistically significant result in a CRCT. Our simulations suggest that only
      with unrealistically favourable study conditions would a statistically
      significant result be likely with 5 years follow-up or less. Small differences in
      the epidemiological parameters between communities can lead to misleading
      incidence rate ratios. Behaviour change independent of the intervention can
      increase the epidemiological impact of the intervention and the chance of
      recording a statistically significant result. CONCLUSIONS: HIV prevention
      interventions, especially those targeted at high-risk groups may take longer to
      work at the population level and need more follow-up time in a CRCT to generate
      statistically significant results. Mathematical modelling can be used in the
      design and analysis of CRCTs to understand how the impact of the intervention
      could develop and the implications this has for statistical power.

PMID- 18096591
TI  - GTP up-regulated persistent Na+ current and enhanced nociceptor excitability
      require NaV1.9.
AB  - Persistent tetrodotoxin-resistant (TTX-r) sodium currents up-regulated by
      intracellular GTP have been invoked as the site of action of peripheral
      inflammatory mediators that lower pain thresholds, and ascribed to the Na(V)1.9
      sodium channel. Here we describe the properties of a global knock-out of Na(V)1.9
      produced by replacing exons 4 and 5 in SCN11A with a neomycin resistance
      cassette, deleting the domain 1 voltage sensor and introducing a frameshift
      mutation. Recordings from small (< 25 microm apparent diameter) sensory neurones
      indicated that channel loss eliminates a TTX-r persistent current. Intracellular
      dialysis of GTP-gamma-S did not cause an up-regulation of persistent Na(+)
      current in Na(V)1.9-null neurones and the concomitant negative shift in voltage
      threshold seen in wild-type and heterozygous neurones. Heterologous hNa(V)1.9
      expression in Na(V)1.9 knock-out sensory neurones confirms that the human clone
      can restore the persistent Na(+) current. Taken together, these findings
      demonstrate that Na(V)1.9 underlies the G-protein pathway-regulated TTX-r
      persistent Na(+) current in small diameter sensory neurones that may drive
      spontaneous discharge in nociceptive nerve fibres during inflammation.

PMID- 18096594
TI  - Really different knockout strains in movement?

PMID- 18096592
TI  - Conduction velocity is regulated by sodium channel inactivation in unmyelinated
      axons innervating the rat cranial meninges.
AB  - Axonal conduction velocity varies according to the level of preceding impulse
      activity. In unmyelinated axons this typically results in a slowing of conduction
      velocity and a parallel increase in threshold. It is currently held that Na(+)
      K(+)-ATPase-dependent axonal hyperpolarization is responsible for this slowing
      but this has long been equivocal. We therefore examined conduction velocity
      changes during repetitive activation of single unmyelinated axons innervating the
      rat cranial meninges. In direct contradiction to the currently accepted
      postulate, Na(+)-K(+)-ATPase blockade actually enhanced activity-induced
      conduction velocity slowing, while the degree of velocity slowing was curtailed
      in the presence of lidocaine (10-300 microm) and carbamazepine (30-500 microm)
      but not tetrodotoxin (TTX, 10-80 nm). This suggests that a change in the number
      of available sodium channels is the most prominent factor responsible for
      activity-induced changes in conduction velocity in unmyelinated axons. At
      moderate stimulus frequencies, axonal conduction velocity is determined by an
      interaction between residual sodium channel inactivation following each impulse
      and the retrieval of channels from inactivation by a concomitant Na(+)-K(+)
      ATPase-mediated hyperpolarization. Since the process is primarily dependent upon
      sodium channel availability, tracking conduction velocity provides a means of
      accessing relative changes in the excitability of nociceptive neurons.

PMID- 18096595
TI  - The role of IKs in atrial arrhythmogenesis.

PMID- 18096596
TI  - Aromatic residues at position 55 of rat alpha7 nicotinic acetylcholine receptors
      are critical for maintaining rapid desensitization.
AB  - The rat alpha7 nicotinic acetylcholine receptor (nAChR) can undergo rapid onset
      of desensitization; however, the mechanisms of desensitization are largely
      unknown. The contribution of a tryptophan (W) residue at position 55 of the rat
      alpha7 nAChR subunit, which lies within the beta2 strand, was studied by mutating
      it to other hydrophobic and/or aromatic amino acids, followed by voltage-clamp
      experiments in Xenopus oocytes. When mutated to alanine, the alpha7-W55A nAChR
      desensitized more slowly, and recovered from desensitization more rapidly, than
      wildtype alpha7 nAChRs. The contribution of desensitization was validated by
      kinetic modelling. Mutating W55 to other aromatic residues (phenylalanine or
      tyrosine) had no significant effect on the kinetics of desensitization, whereas
      mutation to various hydrophobic residues (alanine, cysteine or valine)
      significantly decreased the rate of onset and increased the rate of recovery from
      desensitization. To gain insight into possible structural rearrangements during
      desensitization, we probed the accessibility of W55 by mutating W55 to cysteine
      (alpha7-W55C) and testing the ability of various sulfhydryl reagents to react
      with this cysteine. Several positively charged sulfhydryl reagents blocked ACh
      induced responses for alpha7-W55C nAChRs, whereas a neutral sulfhydryl reagent
      potentiated responses; residue C55 was not accessible for modification in the
      desensitized state. These data suggest that W55 plays an important role in both
      the onset and recovery from desensitization in the rat alpha7 nAChR, and that
      aromatic residues at position 55 are critical for maintaining rapid
      desensitization. Furthermore, these data suggest that W55 may be a potential
      target for modulatory agents operating via hydrophobic interactions.

PMID- 18096597
TI  - Regulation of synaptic signalling by postsynaptic, non-glutamate receptor ion
      channels.
AB  - Activation of glutamatergic synapses onto pyramidal neurons produces a synaptic
      depolarization as well as a buildup of intracellular calcium (Ca(2+)). The
      synaptic depolarization propagates through the dendritic arbor and can be
      detected at the soma with a recording electrode. Current influx through AMPA-type
      glutamate receptors (AMPARs) provides the depolarizing drive, and the amplitudes
      of synaptic potentials are generally thought to reflect the number and properties
      of these receptors at each synapse. In contrast, synaptically evoked Ca(2+)
      transients are limited to the spine containing the active synapse and result
      primarily from Ca(2+) influx through NMDA-type glutamate receptors (NMDARs). Here
      we review recent studies that reveal that both synaptic depolarizations and spine
      head Ca(2+) transients are strongly regulated by the activity of postsynaptic,
      non-glutamate receptor ion channels. In hippocampal pyramidal neurons, voltage-
      and Ca(2+)-gated ion channels located in dendritic spines open as downstream
      consequences of glutamate receptor activation and act within a complex signalling
      loop that feeds back to regulate synaptic signals. Dynamic regulation of these
      ion channels offers a powerful mechanism of synaptic plasticity that is
      independent of direct modulation of glutamate receptors.

PMID- 18096598
TI  - Blunted response to low oxygen of rat respiratory network after perinatal ethanol
      exposure: involvement of inhibitory control.
AB  - Acute ethanol depresses respiration, but little is known about chronic ethanol
      exposure during gestation and breathing, while the deleterious effects of ethanol
      on CNS development have been clearly described. In a recent study we demonstrated
      that pre- and postnatal ethanol exposure induced low minute ventilation in
      juvenile rats. The present study analysed in juvenile rats the respiratory
      response to hypoxia in vivo by plethysmography and the phrenic (Phr) nerve
      response to ischaemia in situ. Glycinergic neurotransmission was assessed in situ
      with strychnine application and [(3)H]strychnine binding experiments performed in
      the medulla. After chronic ethanol exposure, hyperventilation during hypoxia was
      blunted in vivo. In situ Phr nerve response to ischaemia was also impaired, while
      gasping activity occurred earlier and recovery was delayed. Strychnine
      applications in situ (0.05-0.5 microM) demonstrated a higher sensitivity of
      expiratory duration in ethanol-exposed animals compared to control animals.
      Moreover, [(3)H]strychnine binding density was increased after ethanol and was
      associated with higher affinity. Furthermore, 0.2 microM strychnine in ethanol
      exposed animals restored the low basal Phr nerve frequency, but also the Phr
      nerve response to ischaemia and the time to recovery, while gasping activity
      appeared even earlier with a higher frequency. Polycythaemia was present after
      ethanol exposure whereas lung and heart weights were not altered. We conclude
      that chronic ethanol exposure during rat brain development (i) induced
      polycythaemia to compensate for low minute ventilation at rest; (ii) impaired the
      respiratory network adaptive response to low oxygen because of an increase in
      central glycinergic tonic inhibitions, and (iii) did not affect gasping
      mechanisms. We suggest that ethanol exposure during early life can be a risk
      factor for the newborn respiratory adaptive mechanisms to a low oxygen
      environment.

PMID- 18096599
TI  - NKCC1 cotransporter inactivation underlies embryonic development of chloride
      mediated inhibition in mouse spinal motoneuron.
AB  - Early in development, GABA and glycine exert excitatory action that turns to
      inhibition due to modification of the chloride equilibrium potential (E(Cl))
      controlled by the KCC2 and NKCC1 transporters. This switch is thought to be due
      to a late expression of KCC2 associated with a NKCC1 down-regulation. Here, we
      show in mouse embryonic spinal cord that both KCC2 and NKCC1 are expressed and
      functional early in development (E11.5-E13.5) when GABA(A) receptor activation
      induces strong excitatory action. After E15.5, a switch occurs rendering GABA
      unable to provide excitation. At these subsequent stages, NKCC1 becomes both
      inactive and less abundant in motoneurons while KCC2 remains functional and
      hyperpolarizes E(Cl). In conclusion, in contrast to other systems, the
      cotransporters are concomitantly expressed early in the development of the mouse
      spinal cord. Moreover, whereas NKCC1 follows a classical functional extinction,
      KCC2 is highly expressed throughout both early and late embryonic life.

PMID- 18096600
TI  - Properties of human spinal interneurones: normal and dystonic control.
AB  - The muscles that control wrist posture receive large inputs from reflexes driven
      by hand afferents. In several studies, we have investigated these reflexes by
      electrical stimulation of cutaneous (median nerve) and proprioceptive (ulnar
      nerve) afferents from the hand. Median stimulation produced short latency
      inhibition in all motor nuclei investigated, possibly through inhibitory
      propriospinal-like interneurones. Ulnar stimulation produced similar inhibition
      but only in wrist extensors. In the other motor nuclei, ulnar stimulation
      produced short latency excitation mediated by group I motoneuronal drive through
      both monosynaptic and non-monosynaptic pathways involving excitatory
      propriospinal-like interneurones. This was followed by late excitations mediated
      through spinal group II and trans-cortical group I pathways. These results show
      that these pathways are concerned with the integration of afferent inputs,
      proprioceptive and cutaneous, to control of wrist posture during hand movements.
      Patients with focal hand dystonia exhibit abnormal postures. To investigate
      whether these spinal pathways contribute to these conditions, the effects of
      ulnar stimulation on wrist muscle activity during voluntary tonic contraction
      were examined in patients who suffer writer's cramp. Ulnar-induced inhibition of
      the wrist extensors was reduced on the dystonic side of patients compared with
      their normal side and controls. In patients who exhibited abnormal wrist posture,
      group II excitation of the wrist flexors was also modified on the dystonic side.
      Cutaneous stimuli, by contrast, increased wrist flexor EMG on both sides and only
      in patients who exhibited normal posture. We conclude that spinal interneurones
      have a significant role in integrating afferent inputs from the hand to control
      wrist posture during hand movements and that altered function in these spinal
      networks is associated with the complex pathophysiology of writer's cramp.

PMID- 18096601
TI  - Flow-mediated dilatation in the superficial femoral artery is nitric oxide
      mediated in humans.
AB  - Flow-mediated dilatation (FMD) of the brachial and radial arteries is an
      important research tool for assessment of endothelial function in vivo, and is
      nitric oxide (NO) dependent. The leg skeletal muscle vascular bed is an important
      territory for studies in exercise physiology. However, the role of endothelial NO
      in the FMD response of lower limb arteries has never been investigated. The
      purpose of this study was to examine the contribution of NO to FMD in the
      superficial femoral artery in healthy subjects. Since physical inactivity may
      affect endothelial function, and therefore NO availability, spinal cord-injured
      (SCI) individuals were included as a model of extreme deconditioning. In eight
      healthy men (34 +/- 13 years) and six SCI individuals (37 +/- 10 years), the 5
      min FMD response in the superficial femoral artery was assessed by echo-Doppler,
      both during infusion of saline and during infusion of the NO synthase blocker
      N(G)-monomethyl-L-arginine (L-NMMA). In a subset of the controls (n = 6), the 10
      min FMD response was also examined using the same procedure. The 5 min FMD
      response in controls (4.2 +/- 0.3%) was significantly diminished during L-NMMA
      infusion (1.0 +/- 0.2%, P < 0.001). In SCI, L-NMMA also significantly decreased
      the FMD response (from 8.2 +/- 0.4% during saline to 2.4 +/- 0.5% during L-NMMA
      infusion). The hyperaemic flow response during the first 45 s after cuff
      deflation was lower in both groups during infusion of L-NMMA, but the effect of L
      NMMA on FMD persisted in both groups after correction for the shear stress
      stimulus. The 10 min FMD was not affected by L-NMMA (saline: 5.4 +/- 1.6%, L
      NMMA: 5.6 +/- 1.5%). Superficial femoral artery FMD in response to distal
      arterial occlusion for a period of 5 min is predominantly mediated by NO in
      healthy men and in the extremely deconditioned legs of SCI individuals.

PMID- 18096602
TI  - Serotonin differentially modulates the intrinsic properties of spinal motoneurons
      from the adult turtle.
AB  - This report considers serotonergic (5-HT) effects on spinal motoneurons,
      reviewing previous data and presenting a new study showing distinct effects of
      two 5-HT receptor subtypes. We previously investigated the effects of 5-HT on
      motoneurons in a slice preparation from the spinal cord of the adult turtle. In
      agreement with previous studies, we had found that 5-HT applied to the
      extracellular medium promoted a voltage sensitive plateau potential. However, we
      also reported that this effect was only observed in half of the motoneurons; 5-HT
      inhibited the firing of the other half of the motoneurons recorded from. To
      investigate the reasons for this, we applied 5-HT focally by means of the
      microiontophoresis technique. Facilitation of plateau potentials was observed
      when 5-HT was released at sites throughout the somatodendritic region. However,
      motoneurons were inhibited by 5-HT when selectively applied in the perisomatic
      region. These two effects could be induced in the same motoneuron. With
      pharmacological tools, we demonstrate here that the facilitation of plateau
      potentials is mediated by 5-HT(2) receptors and the inhibitory effect is due to
      the activation of 5-HT(1A/7) receptors.

PMID- 18096603
TI  - Hypothalamic input is required for development of normal numbers of thyrotrophs
      and gonadotrophs, but not other anterior pituitary cells in late gestation sheep.
AB  - To evaluate the hypothalamic contribution to the development of anterior
      pituitary (AP) cells we surgically disconnected the hypothalamus from the
      pituitary (hypothalamo-pituitary disconnection, HPD) in fetal sheep and collected
      pituitaries 31 days later. Pituitaries (n = 6 per group) were obtained from fetal
      sheep (term = 147 +/- 3 days) at 110 days (unoperated group) of gestation and at
      141 days from animals that had undergone HPD or sham surgery at 110 days. Cells
      were identified by labelling pituitary sections with antisera against the six AP
      hormones. Additionally, we investigated the colocalization of glycoprotein
      hormones. The proportions of somatotrophs and corticotrophs were unchanged by age
      or HPD. Lactotrophs increased 80% over time, but the proportion was unaffected by
      HPD. Thyrotrophs, which were unaffected by age, increased 70% following HPD.
      Gonadotrophs increased with gestational age (LH+ cells 55%; FSH+ cells 19-fold),
      but this was severely attenuated by HPD. We investigated the possible existence
      of a reciprocal effect of HPD on multipotential glycoprotein-expressing cells. Co
      expression of LH and TSH was extremely rare (< 1%) and unchanged over the last
      month of gestation or HPD. The increase of gonadotrophs expressing FSH only or LH
      and FSH was attenuated by HPD. Therefore, the proportions of somatotrophs,
      lactotrophs and corticotrophs are regulated independently of hypothalamic input
      in the late gestation fetal pituitary. In marked contrast, the determination of
      the thyrotroph and gonadotroph lineages over the same time period is subject to
      complex mechanisms involving hypothalamic factors, which inhibit differentiation
      and/or proliferation of thyrotrophs, but stimulate gonadotrophs down the FSH
      lineage. Development of a distinct population of gonadotrophs, expressing only
      LH, appears to be subject to alternative mechanisms.

PMID- 18096605
TI  - Noggin heterozygous mice: an animal model for congenital conductive hearing loss
      in humans.
AB  - Conductive hearing loss occurs when sound waves are not relayed efficiently to
      the inner ear. Mutations of the NOGGIN (NOG) gene in humans are associated with
      several autosomal dominant disorders such as proximal symphalangism and multiple
      synostoses. These syndromes are characterized by skeletal defects and synostoses,
      which include conductive hearing loss. Noggin is an antagonist of bone
      morphogenetic proteins (BMPs), and balanced levels of BMPs and Noggin are
      required for proper skeletal formation. Depending on the genetic background, some
      of the Nog(+/-) mice display mild hearing loss, that is, conductive in nature.
      Since Noggin is a single exon gene, this data strongly suggest that the autosomal
      dominant disorders associated with NOG mutations are due to haploinsufficiency of
      NOGGIN. The conductive hearing loss in Nog(+/-) mice is caused by an ectopic bone
      bridge located between the stapes and the posterior wall of the tympanum, which
      affects the normal mobility of the ossicle. Our analyses suggest that the ectopic
      bone formation is caused by a failure of the stapes and styloid process to
      separate completely during development. This failure of bone separation in the
      Nog(+/-) mice reveals another consequence of chondrocyte hyperplasia due to
      unopposed Bmp activities in these mutants such as Bmp4 and Bmp14 (Gdf5). More
      importantly, these results establish Nog(+/-) mice as the first animal model for
      the study of conductive rather than neurosensory hearing loss that has direct
      relevance to human genetic disorders.

PMID- 18096604
TI  - Modification of K+ channel-drug interactions by ancillary subunits.
AB  - Reconciling ion channel alpha-subunit expression with native ionic currents and
      their pharmacological sensitivity in target organs has proved difficult. In
      native tissue, many K(+) channel alpha-subunits co-assemble with ancillary
      subunits, which can profoundly affect physiological parameters including gating
      kinetics and pharmacological interactions. In this review, we examine the link
      between voltage-gated potassium ion channel pharmacology and the biophysics of
      ancillary subunits. We propose that ancillary subunits can modify the interaction
      between pore blockers and ion channels by three distinct mechanisms: changes in
      (1) binding site accessibility; (2) orientation of pore-lining residues; (3) the
      ability of the channel to undergo post-binding conformational changes. Each of
      these subunit-induced changes has implications for gating, drug affinity and use
      dependence of their respective channel complexes. A single subunit may modulate
      its associated alpha-subunit by more than one of these mechanisms. Voltage-gated
      potassium channels are the site of action of many therapeutic drugs. In addition,
      potassium channels interact with drugs whose primary target is another channel,
      e.g. the calcium channel blocker nifedipine, the sodium channel blocker
      quinidine, etc. Even when K(+) channel block is the intended mode of action,
      block of related channels in non-target organs, e.g. the heart, can result in
      major and potentially lethal side-effects. Understanding factors that determine
      specificity, use dependence and other properties of K(+) channel drug binding are
      therefore of vital clinical importance. Ancillary subunits play a key role in
      determining these properties in native tissue, and so understanding channel
      subunit interactions is vital to understanding clinical pharmacology.

PMID- 18096606
TI  - Active and inactive pools of nNOS in the nerve terminals in mouse gut:
      implications for nitrergic neurotransmission.
AB  - Nitric oxide (NO) is responsible for nitrergic neurotransmission in the gut, and
      its release is dependent on its de novo synthesis by neuronal nitric oxide
      synthase (nNOS). The magnitude of NO synthesis and release during
      neurotransmission may be related to the fraction of catalytically active nNOS out
      of a larger pool of inactive nNOS in the nerve terminals. The purpose of the
      present study was to identify catalytically active and inactive pools of nNOS in
      the varicosities from mouse gut. Enteric varicosities were confirmed as nitrergic
      by colocalization of nNOS with the nerve varicosity marker synaptophysin. Low
      temperature SDS-PAGE of these varicosity extracts showed 320-, 250-, and 155-kDa
      bands when blotted with anti-nNOS(1422-1433) and 320- and 155-kDa bands when
      blotted with anti-nNOS(1-20) antibodies, respectively. The 320- and 155-kDa bands
      represent dimers and monomers of nNOSalpha; the 250- and 135-kDa bands represent
      dimers and monomers of nNOSbeta. Immunoprecipitation with calmodulin (CaM) showed
      that a portion of nNOSalpha dimer was bound with CaM. On the other hand, a
      portion of nNOSalpha dimer, nNOSbeta dimer, and all monomers lacked CaM binding.
      The CaM-lacking nNOS fractions reacted with anti-serine 847-phospho-nNOS. In
      vitro assays of NO production revealed that only the CaM-bound dimeric nNOSalpha
      was catalytically active; all other forms were inactive. We suggest that the
      amount of catalytically active nNOSalpha dimers may be regulated by serine 847
      phosphorylation and equilibrium between dimers and monomers of nNOSalpha.

PMID- 18096607
TI  - New primary culture systems to study the differentiation and proliferation of
      mouse fetal hepatoblasts.
AB  - Hepatoblasts have the potential to differentiate into both hepatocytes and
      biliary epithelial cells through a differentiation program that has not been
      fully elucidated. With the aim to better define the mechanism of differentiation
      of hepatoblasts, we isolated hepatoblasts and established new culture systems. We
      isolated hepatoblasts from E12.5 fetal mouse liver by using E-cadherin. The E
      cadherin+ cells expressed alpha-fetoprotein (AFP) and albumin (Alb) but not
      cytokeratin 19 (CK19). Transplantation of the E-cadherin+ cells into mice that
      had been subjected to liver injury or biliary epithelial injury led to
      differentiation of the cells into hepatocytes or biliary epithelial cells,
      respectively. In a low-cell-density culture system in the absence of additional
      growth factors, E-cadherin+ cells formed colonies of various sizes, largely
      comprising Alb-positive cells. Supplementation of the culture medium with
      hepatocyte growth factor and epidermal growth factor promoted proliferation of
      the cells. Thus the low-cell-density culture system should be useful to identify
      inductive factors that regulate the proliferation and differentiation of
      hepatoblasts. In a high-cell-density system in the presence of oncostatin
      M+dexamethasone, E14.5, but not E12.5, E-cadherin+ cells differentiated into
      mature hepatocytes, suggesting that unidentified factors are involved in hepatic
      maturation. Culture of E-cadherin+ cells derived from E12.5 or E14.5 liver under
      high-cell-density conditions should allow elucidation of the mechanism of hepatic
      differentiation in greater detail. These new culture systems should be of use to
      identify growth factors that induce hepatoblasts to proliferate or differentiate
      into hepatocytes and biliary epithelial cells.

PMID- 18096608
TI  - Anandamide inhibits cholangiocyte hyperplastic proliferation via activation of
      thioredoxin 1/redox factor 1 and AP-1 activation.
AB  - The endocannabinoid system regulates various aspects of hepatic fibrosis;
      however, nothing is known about its role in regulating cholangiocyte
      proliferation and function. We evaluated the effects of anandamide (AEA) on
      cholangiocyte proliferation and explored the effects of AEA on the thioredoxin 1
      (TRX1)/redox factor 1 (Ref1)/activator protein-1 (AP-1) pathway. Mice underwent
      bile duct ligation (BDL) and were infused with AEA for 3 days postsurgery.
      Proliferation and apoptosis were evaluated in liver sections. Effects of in vitro
      AEA treatment on cholangiocyte proliferation and apoptosis were studied in
      purified cholangiocytes. The relative expression of cannabinoid receptors was
      also assessed in liver sections and cholangiocytes. mRNA expression of the
      cannabinoid receptors Cb1 and VR1 was decreased after BDL, whereas there was an
      upregulation of Cb2 mRNA. AEA decreased cholangiocyte growth and induced
      accumulation of reactive oxygen species, upregulation of TRX1, Ref1, c-Fos, and c
      Jun expression, increased nuclear localization of TRX1, and increased AP-1
      transcriptional activity. Specific knockdown of TRX1 or Ref1 expression ablated
      the AP-1 transcriptional activity and AEA-induced cell death but not expression
      of c-Fos and c-Jun. Knockdown of c-Fos and c-Jun expression also ablated AEA
      induced apoptosis. We conclude that AEA suppresses cholangiocyte proliferation
      during cholestasis via a Cb2-dependent mechanism. Modulation of the
      endocannabinoid system may be important in the treatment of cholangiopathies.

PMID- 18096609
TI  - Differential regulation of ERK1/2 and p38 MAP kinases in VacA-induced apoptosis
      of gastric epithelial cells.
AB  - Helicobacter pylori vacuolating cytotoxin A (VacA) has been considered as an
      apoptosis-inducing factor. Here, we investigated the mechanism of VacA-induced
      apoptosis in relation to the defense mechanism and MAP kinases pathway in gastric
      epithelial cells. AGS cells exposed to enriched VacA extracts affected the level
      of SOD-1 and villin. We further investigated the role of VacA in those inductions
      using a functional recombinant VacA (rVacA). Activation of p38 MAPK and Bax
      dimerization by rVacA were increased in a dose-dependent manner. rVacA-induced
      ERK1/2 MAPK activation was maximal at 30 min and 4 h and 1-4 microg/ml of rVacA.
      rVacA-induced SOD-1 expression was considerably diminished by inhibiting ERK1/2
      MAPK and it was slightly increased by inhibiting p38 MAPK. rVacA increased or
      decreased villin expression depending on dose and exposure time and its
      expression was mainly appeared in the contractile actin ring of the dividing
      cells. Despite its cytoprotective effect, SB-203580, a p38 inhibitor, was
      unlikely to reduce VacA-induced Bax dimerization and rather inhibited villin and
      Bcl2 expression, indicating that p38 may also play a role in cell proliferation
      or differentiation for survival after VacA intoxication. Furthermore, p38
      inhibitor accelerated rVacA-induced cell death after exposure of AGS cells to
      H(2)O(2) but ERK1/2 inhibitor protected cells from H(2)O(2) insult. These results
      suggest that SOD-1 and villin are expressed differentially upon VacA insult
      depending on dose and exposure time via ERK and p38 MAP kinases; decrease in SOD
      1 and villin expression coupled with Bax dimerization leads to apoptosis of
      gastric epithelial cells.

PMID- 18096610
TI  - JAM-A is both essential and inhibitory to development of hepatic polarity in WIF
      B cells.
AB  - Junctional adhesion molecule (JAM) is involved in tight junction (TJ) formation
      in epithelial cells. Three JAMs (A, B, and C) are expressed in rat hepatocytes,
      but only rat JAM-A is present in polarized WIF-B cells, a rat-human hepatic line.
      We used knockdown (KD) and overexpression in WIF-B cells to determine the role of
      JAM-A in the development of hepatic polarity. Expression of rat JAM-A short
      hairpin RNA resulted in approximately 50% KD of JAM-A and substantial loss of
      hepatic polarity, as measured by the absence of apical cysts formed by adjacent
      cells and sealed by TJ belts. When inhibitory RNA-resistant human JAM-A (huWT)
      was expressed in KD cells, hepatic polarity was restored. In contrast, expression
      of JAM-A that either lacked its PDZ-binding motif (huDeltaC-term) or harbored a
      point mutation (T273A) did not complement, indicating that multiple sites within
      JAM-A's cytoplasmic tail are required for the development of hepatic polarity.
      Overexpression of huWT in normal WIF-B cells unexpectedly blocked WIF-B
      maturation to the hepatic phenotype, as did expression of three huJAM-A
      constructs with single point mutations in putative phosphorylation sites. In
      contrast, huDeltaC-term was without effect, and the T273A mutant only partially
      blocked maturation. Our results show that JAM-A is essential for the development
      of polarity in cultured hepatic cells via its possible phosphorylation and
      recruitment of relevant PDZ proteins and that hepatic polarity is achieved within
      a narrow range of JAM-A expression levels. Importantly, formation/maintenance of
      TJs and the apical domain in hepatic cells are linked, unlike simple epithelia.

PMID- 18096611
TI  - Deficiency of intramuscular ICC increases fundic muscle excitability but does not
      impede nitrergic innervation.
AB  - The motility of the gastrointestinal tract is generated by smooth muscle cells
      and is controlled to a large extent by an intrinsic neural network. A gap of
      approximately 200 nm usually separates nerve varicosities from smooth muscle
      cells, which suggests that direct innervation of the smooth muscle by synapses
      does not occur. Enteric nerves do make synapse-like contact with proposed
      regulatory cells, the interstitial cells of Cajal (ICC), which in turn may be in
      gap junction contact with smooth muscle cells. The role played by ICC in enteric
      innervation is controversial. Experimental evidence has been presented in vitro
      for the hypothesis that nitrergic inhibitory innervation is strongly reduced in
      the absence of ICC. However, in vivo data appear to dispute that. The present
      report provides evidence that explains the discrepancy between in vivo and in
      vitro data and provides evidence that inhibitory neurotransmitters can reach
      smooth muscle cells without hindrance when ICC are absent. The fundic musculature
      shows increased responses to substance P-mediated innervation and shows marked
      spontaneous activity, which is consistent with increased muscle excitability.

PMID- 18096612
TI  - AlterORF: a database of alternate open reading frames.
AB  - AlterORF is a searchable database that contains information regarding alternate
      open reading frames (ORFs) for over 1.5 million genes in 481 prokaryotic genomes.
      The objective of the database is to provide a platform for improving genome
      annotation and to serve as an aid for the identification of prokaryotic genes
      that potentially encode proteins in more than one reading frame. The AlterORF
      Database can be accessed through a web interface at www.alterorf.cl.

PMID- 18096613
TI  - 2'-Methylseleno-modified oligoribonucleotides for X-ray crystallography
      synthesized by the ACE RNA solid-phase approach.
AB  - Site-specifically modified 2'-methylseleno RNA represents a valuable derivative
      for phasing of X-ray crystallographic data. Several successful applications in
      three-dimensional structure determination of nucleic acids, such as the Diels
      Alder ribozyme, have relied on this modification. Here, we introduce synthetic
      routes to 2'-methylseleno phosphoramidite building blocks of all four standard
      nucleosides, adenosine, cytidine, guanosine and uridine, that are tailored for 2'
      O-bis(acetoxyethoxy)methyl (ACE) RNA solid-phase synthesis. We additionally
      report on their incorporation into oligoribonucleotides including deprotection
      and purification. The methodological expansion of 2'-methylseleno labeling via
      ACE RNA chemistry is a major step to make Se-RNA generally accessible and to
      receive broad dissemination of the Se-approach for crystallographic studies on
      RNA. Thus far, preparation of 2'-methylseleno-modified oligoribonucleotides has
      been restricted to the 2'-O-[(triisopropylsilyl)oxy]methyl (TOM) and 2'-O-tert
      butyldimethylsilyl (TBDMS) RNA synthesis methods.

PMID- 18096614
TI  - HU binds and folds single-stranded DNA.
AB  - The nucleoid-associated protein HU plays an important role in bacterial nucleoid
      organization and is involved in numerous processes including transposition,
      recombination and DNA repair. We show here that HU binds specifically DNA
      containing mismatched region longer than 3 bp as well as DNA bulges. HU binds
      single-stranded DNA (ssDNA) in a binding mode that is reminiscent but different
      from earlier reported specific HU interactions with double-helical DNA lesions.
      An HU dimer requires 24 nt of ssDNA for initial binding, and 12 nt of ssDNA for
      each additional dimer binding. In the presence of equimolar amounts of HU dimer
      and DNA, the ssDNA molecule forms an U-loop (hairpin-like) around the protein,
      providing contacts with both sides of the HU body. This mode differs from the
      binding of the single-strand-binding protein (SSB) to ssDNA: in sharp contrast to
      SSB, HU binds ssDNA non-cooperatively and does not destabilize double-helical
      DNA. Furthermore HU has a strong preference for poly(dG), while binding to
      poly(dA) is the weakest. HU binding to ssDNA is probably important for its
      capacity to cover and protect bacterial DNA both intact and carrying lesions.

PMID- 18096615
TI  - Knockdown of TNFR1 by the sense strand of an ICAM-1 siRNA: dissection of an off
      target effect.
AB  - Tumor necrosis factor (TNF) initiates local inflammation by triggering
      endothelial cells (EC) to express adhesion molecules for leukocytes such as
      intercellular adhesion molecule-1 (ICAM-1 or CD54). A prior study identified
      siRNA molecules that reduce ICAM-1 expression in cultured human umbilical vein EC
      (HUVEC). One of these, ISIS 121736, unexpectedly inhibits TNF-mediated up
      regulation of additional molecules on EC, including E-selectin (CD62E), VCAM-1
      (CD106) and HLA-A,B,C. 736 siRNA transfection was not toxic for EC nor was there
      any evidence of an interferon response. 736 Transfection of EC blocked multiple
      early TNF-related signaling events, including activation of NF-kappaB. IL-1
      activation of these same pathways was not inhibited. A unifying explanation is
      that 736 siRNA specifically reduced expression of mRNA encoding tumor necrosis
      factor receptor 1 (TNFR1) as well as TNFR1 surface expression. A sequence with
      high identity to the 736 antisense strand (17 of 19 bases) is present within the
      3'UTR of human TNFR1 mRNA. An EGFP construct incorporating the 3'UTR of TNFR1 was
      silenced by 736 siRNA and this effect was lost by mutagenesis of this
      complementary sequence. Chemical modification and mismatches within the sense
      strand of 736 also inhibited silencing activity. In summary, an siRNA molecule
      selected to target ICAM-1 through its antisense strand exhibited broad anti-TNF
      activities. We show that this off-target effect is mediated by siRNA knockdown of
      TNFR1 via its sense strand. This may be the first example in which the off-target
      effect of an siRNA is actually responsible for the anticipated effect by acting
      to reduce expression of a protein (TNFR1) that normally regulates expression of
      the intended target (ICAM-1).

PMID- 18096616
TI  - Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced
      protein kinase PKR.
AB  - PKR is an interferon (IFN)-induced protein kinase, which is involved in
      regulation of antiviral innate immunity, stress signaling, cell proliferation and
      programmed cell death. Although a low amount of PKR is expressed ubiquitously in
      all cell types in the absence of IFNs, PKR expression is induced at
      transcriptional level by IFN. PKR's enzymatic activity is activated by its
      binding to one of its activators. Double-stranded (ds) RNA, protein activator
      PACT and heparin are the three known activators of PKR. Activation of PKR in
      cells leads to a general block in protein synthesis due to phosphorylation of
      eIF2alpha on serine 51 by PKR. PKR activation is regulated very tightly in
      mammalian cells and a prolonged activation of PKR leads to apoptosis. Thus,
      positive and negative regulation of PKR activation is important for cell
      viability and function. The studies presented here describe human dihydrouridine
      synthase-2 (hDUS2) as a novel regulator of PKR. We originally identified hDUS2 as
      a protein interacting with PACT in a yeast two-hybrid screen. Further
      characterization revealed that hDUS2 also interacts with PKR through its dsRNA
      binding/dimerization domain and inhibits its kinase activity. Our results suggest
      that hDUS2 may act as a novel inhibitor of PKR in cells.

PMID- 18096617
TI  - Biochemical and structural characterization of Cren7, a novel chromatin protein
      conserved among Crenarchaea.
AB  - Archaea contain a variety of chromatin proteins consistent with the evolution of
      different genome packaging mechanisms. Among the two main kingdoms in the
      Archaea, Euryarchaeota synthesize histone homologs, whereas Crenarchaeota have
      not been shown to possess a chromatin protein conserved at the kingdom level. We
      report the identification of Cren7, a novel family of chromatin proteins highly
      conserved in the Crenarchaeota. A small, basic, methylated and abundant protein,
      Cren7 displays a higher affinity for double-stranded DNA than for single-stranded
      DNA, constrains negative DNA supercoils and is associated with genomic DNA in
      vivo. The solution structure and DNA-binding surface of Cren7 from the
      hyperthermophilic crenarchaeon Sulfolobus solfataricus were determined by NMR.
      The protein adopts an SH3-like fold. It interacts with duplex DNA through a beta
      sheet and a long flexible loop, presumably resulting in DNA distortions through
      intercalation of conserved hydrophobic residues into the DNA structure. These
      data suggest that the crenarchaeal kingdom in the Archaea shares a common
      strategy in chromatin organization.

PMID- 18096618
TI  - Mutation adjacent to the active site tyrosine can enhance DNA cleavage and cell
      killing by the TOPRIM Gly to Ser mutant of bacterial topoisomerase I.
AB  - The TOPRIM DXDXXG residues of type IA and II topoisomerases are involved in
      Mg(II) binding and the cleavage-rejoining of DNA. Mutation of the strictly
      conserved glycine to serine in Yersinia pestis and Escherichia coli topoisomerase
      I results in bacterial cell killing due to inhibition of DNA religation after DNA
      cleavage. In this study, all other substitutions at the TOPRIM glycine of Y.
      pestis topoisomerase I were examined. While the Gly to Ala substitution allowed
      both DNA cleavage and religation, other mutations abolished DNA cleavage. DNA
      cleavage activity retained by the Gly to Ser mutant could be significantly
      enhanced by a second mutation of the methionine residue adjacent to the active
      site tyrosine. Induction of mutant topoisomerase with both the TOPRIM glycine and
      active site region methionine mutations resulted in up to 40-fold higher cell
      killing rate when compared with the single TOPRIM Gly to Ser mutant. Bacterial
      type IA topoisomerases are potential targets for discovery of novel antibiotics.
      These results suggest that compounds that interact simultaneously with the TOPRIM
      motif and the molecular surface around the active site tyrosine could be highly
      efficient topoisomerase poisons through both enhancement of DNA cleavage and
      inhibition of DNA rejoining.

PMID- 18096619
TI  - Kinking the double helix by bending deformation.
AB  - DNA bending and torsional deformations that often occur during its functioning
      inside the cell can cause local disruptions of the regular helical structure. The
      disruptions created by negative torsional stress have been studied in detail, but
      those caused by bending stress have only been analyzed theoretically. By probing
      the structure of very small DNA circles, we determined that bending stress
      disrupts the regular helical structure when the radius of DNA curvature is
      smaller than 3.5 nm. First, we developed an efficient method to obtain covalently
      closed DNA minicircles. To detect structural disruptions in the minicircles we
      treated them by single-strand-specific endonucleases. The data showed that the
      regular DNA structure is disrupted by bending deformation in the 64-65-bp
      minicircles, but not in the 85-86-bp minicircles. Our results suggest that strong
      DNA bending initiates kink formation while preserving base pairing.

PMID- 18096620
TI  - Assembly and structural analysis of a covalently closed nano-scale DNA cage.
AB  - The inherent properties of DNA as a stable polymer with unique affinity for
      partner molecules determined by the specific Watson-Crick base pairing makes it
      an ideal component in self-assembling structures. This has been exploited for
      decades in the design of a variety of artificial substrates for investigations of
      DNA-interacting enzymes. More recently, strategies for synthesis of more complex
      two-dimensional (2D) and 3D DNA structures have emerged. However, the building of
      such structures is still in progress and more experiences from different research
      groups and different fields of expertise are necessary before complex DNA
      structures can be routinely designed for the use in basal science and/or
      biotechnology. Here we present the design, construction and structural analysis
      of a covalently closed and stable 3D DNA structure with the connectivity of an
      octahedron, as defined by the double-stranded DNA helices that assembles from
      eight oligonucleotides with a yield of approximately 30%. As demonstrated by
      Small Angle X-ray Scattering and cryo-Transmission Electron Microscopy analyses
      the eight-stranded DNA structure has a central cavity larger than the apertures
      in the surrounding DNA lattice and can be described as a nano-scale DNA cage,
      Hence, in theory it could hold proteins or other bio-molecules to enable their
      investigation in certain harmful environments or even allow their organization
      into higher order structures.

PMID- 18096621
TI  - Site-specific recombination in Schizosaccharomyces pombe and systematic assembly
      of a 400kb transgene array in mammalian cells using the integrase of Streptomyces
      phage phiBT1.
AB  - We have established the integrase of the Streptomyces phage phiBT1 as a tool for
      eukaryotic genome manipulation. We show that the phiBT1 integrase promotes
      efficient reciprocal and conservative site-specific recombination in vertebrate
      cells and in Schizosaccharomyces pombe, thus establishing the utility of this
      protein for genome manipulation in a wide range of eukaryotes. We show that the
      phiBT1 integrase can be used in conjunction with Cre recombinase to promote the
      iterative integration of transgenic DNA. We describe five cycles of iterative
      integration of a candidate mouse centromeric sequence 80 kb in length into a
      human mini-chromosome within a human-Chinese hamster hybrid cell line. These
      results establish the generality of the iterative site-specific integration
      technique.

PMID- 18096622
TI  - Kluyveromyces lactis gamma-toxin, a ribonuclease that recognizes the anticodon
      stem loop of tRNA.
AB  - Kluyveromyces lactis gamma-toxin is a tRNA endonuclease that cleaves
      Saccharomyces cerevisiae [see text] between position 34 and position 35. All
      three substrate tRNAs carry a 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U)
      residue at position 34 (wobble position) of which the mcm(5) group is required
      for efficient cleavage. However, the different cleavage efficiencies of
      mcm(5)s(2)U(34)-containing tRNAs suggest that additional features of these tRNAs
      affect cleavage. In the present study, we show that a stable anticodon stem and
      the anticodon loop are the minimal requirements for cleavage by gamma-toxin. A
      synthetic minihelix RNA corresponding to the anticodon stem loop (ASL) of the
      natural substrate [see text] is cleaved at the same position as the natural
      substrate. In [see text], the nucleotides U(34)U(35)C(36)A(37)C(38) are required
      for optimal gamma-toxin cleavage, whereas a purine at position 32 or a G in
      position 33 dramatically reduces the cleavage of the ASL. Comparing modified and
      partially modified forms of E. coli and yeast [see text] reinforced the strong
      stimulatory effects of the mcm(5) group, revealed a weak positive effect of the
      s(2) group and a negative effect of the bacterial 5-methylaminomethyl (mnm(5))
      group. The data underscore the high specificity of this yeast tRNA toxin.

PMID- 18096623
TI  - Role of poly (A) tail as an identity element for mRNA nuclear export.
AB  - Different RNA species are rigorously discriminated and exported by distinct
      export factors, but this discrimination mechanism remains largely unknown. We
      previously showed, by RNA microinjection experiments, that intronless mRNAs are
      discriminated from U snRNAs based on their difference in RNA length. However, it
      was unclear how they are discriminated in the natural situation in which their
      nascent transcripts emerge progressively during transcription. We hypothesized
      that transcription from the corresponding promoters is important for this
      discrimination. Here we show that contrary to our hypothesis, the discrimination
      process was not significantly influenced by whether transcription occurred from
      an mRNA- versus a U snRNA-type promoter. Rather, the features of transcribed RNAs
      determined the RNA identity, consistent with our previous results of RNA
      microinjection. Moreover, we found that the poly (A) tail can function as an
      identity element for mRNA export. The presence of a poly (A) tail of an
      appropriate length committed otherwise short Pol II transcripts to the mRNA
      export pathway in a dominant manner, indicating that the poly (A) tail either
      contributes to increasing the RNA length or functions as a platform to recruit
      mRNA export factors. Our results reveal a novel function of the poly (A) tail in
      mRNA export.

PMID- 18096624
TI  - AZT resistance of simian foamy virus reverse transcriptase is based on the
      excision of AZTMP in the presence of ATP.
AB  - Azidothymidine (AZT, zidovudine) is one of the few nucleoside inhibitors known to
      inhibit foamy virus replication. We have shown previously that up to four
      mutations in the reverse transcriptase gene of simian foamy virus from macaque
      (SFVmac) are necessary to confer high resistance against AZT. To characterize the
      mechanism of AZT resistance we expressed two recombinant reverse transcriptases
      of highly AZT-resistant SFVmac in Escherichia coli harboring three (K211I, S345T,
      E350K) or four mutations (K211I, I224T, S345T, E350K) in the reverse
      transcriptase gene. Our analyses show that the polymerization activity of these
      mutants is impaired. In contrast to the AZT-resistant reverse transcriptase of
      HIV-1, the AZT resistant enzymes of SFVmac reveal differences in their kinetic
      properties. The SFVmac enzymes exhibit lower specific activities on
      poly(rA)/oligo(dT) and higher K(M)-values for polymerization but no change in
      K(D)-values for DNA/DNA or RNA/DNA substrates. The AZT resistance of the mutant
      enzymes is based on the excision of the incorporated inhibitor in the presence of
      ATP. The additional amino acid change of the quadruple mutant appears to be
      important for regaining polymerization efficiency.

PMID- 18096625
TI  - Loop dependence of the stability and dynamics of nucleic acid hairpins.
AB  - Hairpin loops are critical to the formation of nucleic acid secondary structure,
      and to their function. Previous studies revealed a steep dependence of single
      stranded DNA (ssDNA) hairpin stability with length of the loop (L) as
      approximately L(8.5 +/- 0.5), in 100 mM NaCl, which was attributed to intraloop
      stacking interactions. In this article, the loop-size dependence of RNA hairpin
      stabilities and their folding/unfolding kinetics were monitored with laser
      temperature-jump spectroscopy. Our results suggest that similar mechanisms
      stabilize small ssDNA and RNA loops, and show that salt contributes significantly
      to the dependence of hairpin stability on loop size. In 2.5 mM MgCl2, the
      stabilities of both ssDNA and RNA hairpins scale as approximately L(4 +/- 0.5),
      indicating that the intraloop interactions are weaker in the presence of Mg2+.
      Interestingly, the folding times for ssDNA hairpins (in 100 mM NaCl) and RNA
      hairpins (in 2.5 mM MgCl2) are similar despite differences in the salt conditions
      and the stem sequence, and increase similarly with loop size, approximately L(2.2
      +/- 0.5) and approximately L(2.6 +/- 0.5), respectively. These results suggest
      that hairpins with small loops may be specifically stabilized by interactions of
      the Na+ ions with the loops. The results also reinforce the idea that folding
      times are dominated by an entropic search for the correct nucleating
      conformation.

PMID- 18096627
TI  - Mapping the number of molecules and brightness in the laser scanning microscope.
AB  - We describe a technique based on moment-analysis for the measurement of the
      average number of molecules and brightness in each pixel in fluorescence
      microscopy images. The average brightness of the particle is obtained from the
      ratio of the variance to the average intensity at each pixel. To obtain the
      average number of fluctuating particles, we divide the average intensity at one
      pixel by the brightness. This analysis can be used in a wide range of
      concentrations. In cells, the intensity at any given pixel may be due to bright
      immobile structures, dim fast diffusing particles, and to autofluorescence or
      scattering. The total variance is given by the variance of each of the above
      components in addition to the variance due to detector noise. Assuming that all
      sources of variance are independent, the total variance is the sum of the
      variances of the individual components. The variance due to the particles
      fluctuating in the observation volume is proportional to the square of the
      particle brightness while the variance of the immobile fraction, the
      autofluorescence, scattering, and that of the detector is proportional to the
      intensity of these components. Only the fluctuations that depend on the square of
      the brightness (the mobile particles) will have a ratio of the variance to the
      intensity >1. Furthermore, changing the fluorescence intensity by increasing the
      illumination power, distinguishes between these possible contributions. We show
      maps of molecular brightness and number of cell migration proteins obtained using
      a two-photon scanning microscope operating with a photon-counting detector. These
      brightness maps reveal binding dynamics at the focal adhesions with pixel
      resolution and provide a picture of the binding and unbinding process in which
      dim molecules attach to the adhesions or large molecular aggregates dissociate
      from adhesion.

PMID- 18096626
TI  - Targeted induction of meiotic double-strand breaks reveals chromosomal domain
      dependent regulation of Spo11 and interactions among potential sites of meiotic
      recombination.
AB  - Meiotic recombination is initiated by programmed DNA double-strand break (DSB)
      formation mediated by Spo11. DSBs occur with frequency in chromosomal regions
      called hot domains but are seldom seen in cold domains. To obtain insights into
      the determinants of the distribution of meiotic DSBs, we examined the effects of
      inducing targeted DSBs during yeast meiosis using a UAS-directed form of Spo11
      (Gal4BD-Spo11) and a meiosis-specific endonuclease, VDE (PI-SceI). Gal4BD-Spo11
      cleaved its target sequence (UAS) integrated in hot domains but rarely in cold
      domains. However, Gal4BD-Spo11 did bind to UAS and VDE efficiently cleaved its
      recognition sequence in either context, suggesting that a cold domain is not a
      region of inaccessible or uncleavable chromosome structure. Importantly, self
      association of Spo11 occurred at UAS in a hot domain but not in a cold domain,
      raising the possibility that Spo11 remains in an inactive intermediate state in
      cold domains. Integration of UAS adjacent to known DSB hotspots allowed us to
      detect competitive interactions among hotspots for activation. Moreover, the
      presence of VDE-introduced DSB repressed proximal hotspot activity, implicating
      DSBs themselves in interactions among hotspots. Thus, potential sites for Spo11
      mediated DSB are subject to domain-specific and local competitive regulations
      during and after DSB formation.

PMID- 18096628
TI  - Interleaflet coupling mechanisms in bilayers of lipids and cholesterol.
AB  - Whereas it appears to be generally believed that the leaflets of a
      phospholipid/cholesterol bilayer interact with each other in some way, the exact
      mechanism remains undetermined. Various suggestions have been invoked, including
      chain interdigitation and rapid translocation of cholesterol. There is little, if
      any, direct evidence supporting or excluding these hypotheses. In this letter, I
      examine a few different possibilities. Chain interdigitation is unlikely to be
      significant. Cholesterol translocation meets some, though not all, of the
      relevant criteria, and probably plays an important role. The simplest explanation
      is that the layers interact at the midplane in the same way that the ordered and
      disordered liquid phases common in these systems interact at their interfaces. A
      quick estimate of that interfacial energy shows that this is a very likely
      candidate. The consequences of such an energy in biological systems are briefly
      considered.

PMID- 18096629
TI  - Yeast ribosomal stalk heterogeneity in vivo shown by two-photon FCS and molecular
      brightness analysis.
AB  - The stalk of Saccharomyces cerevisiae ribosomes contains, on average, five
      distinct proteins, namely P0 and four acidic proteins, P1alpha, P1beta, P2alpha,
      and P2beta. Each ribosome contains only one copy of P0, but the distribution of
      the acidic proteins among the ribosome population in vivo has not been
      determined. Using two-photon fluorescence correlation spectroscopy and scanning
      FCS, on cells expressing EGFP-tagged P0, P1, and P2 proteins, we show, with
      brightness analysis, that individual yeast ribosomes in vivo are compositionally
      heterogeneous in regard to P1alpha, P1beta, P2alpha, and P2beta. These results
      are relevant to the hypothesis, based on in vitro studies, that the overall
      cellular pattern of expressed proteins can be determined by the distribution of
      the stalk proteins among the ribosome population.

PMID- 18096630
TI  - Experimental and computational studies investigating trehalose protection of
      HepG2 cells from palmitate-induced toxicity.
AB  - Understanding the mechanism of saturated fatty acid-induced hepatocyte toxicity
      may provide insight into cures for diseases such as obesity-associated cirrhosis.
      Trehalose, a nonreducing disaccharide shown to protect proteins and cellular
      membranes from inactivation or denaturation caused by different stress
      conditions, also protects hepatocytes from palmitate-induced toxicity. Our
      results suggest that trehalose serves as a free radical scavenger and alleviates
      damage from hydrogen peroxide secreted by the compromised cells. We also observe
      that trehalose protects HepG2 cells by interacting with the plasma membrane to
      counteract the changes in membrane fluidity induced by palmitate. The
      experimental results are supported by molecular dynamics simulations of model
      cell membranes that closely reflect the experimental conditions. Simulations were
      performed to understand the specific interactions between lipid bilayers,
      palmitate, and trehalose. The simulations results reveal the early stages of how
      palmitate induces biophysical changes to the cellular membrane and the role of
      trehalose in protecting the membrane structure.

PMID- 18096631
TI  - Spatial regulation improves antiparallel microtubule overlap during mitotic
      spindle assembly.
AB  - The mitotic spindle plays an essential role in chromosome segregation during cell
      division. Spindle formation and proper function require that microtubules with
      opposite polarity overlap and interact. Previous computational simulations have
      demonstrated that these antiparallel interactions could be created by complexes
      combining plus- and minus-end-directed motors. The resulting spindles, however,
      exhibit sparse antiparallel microtubule overlap with motor complexes linking only
      a nominal number of antiparallel microtubules. Here we investigate the role that
      spatial differences in the regulation of microtubule interactions can have on
      spindle morphology. We show that the spatial regulation of microtubule
      catastrophe parameters can lead to significantly better spindle morphology and
      spindles with greater antiparallel MT overlap. We also demonstrate that
      antiparallel microtubule overlap can be increased by having new microtubules
      nucleated along the length of existing astral microtubules, but this increase
      negatively affects spindle morphology. Finally, we show that limiting the
      diffusion of motor complexes within the spindle region increases antiparallel
      microtubule interaction.

PMID- 18096632
TI  - Backbone dynamics of alamethicin bound to lipid membranes: spin-echo electron
      paramagnetic resonance of TOAC-spin labels.
AB  - Alamethicin F50/5 is a hydrophobic peptide that is devoid of charged residues and
      that induces voltage-dependent ion channels in lipid membranes. The peptide
      backbone is likely to be involved in the ion conduction pathway. Electron spin
      echo spectroscopy of alamethicin F50/5 analogs in which a selected Aib residue
      (at position n = 1, 8, or 16) is replaced by the TOAC amino-acid spin label was
      used to study torsional dynamics of the peptide backbone in association with
      phosphatidylcholine bilayer membranes. Rapid librational motions of limited
      angular amplitude were observed at each of the three TOAC sites by recording echo
      detected spectra as a function of echo delay time, 2tau. Simulation of the time
      resolved spectra, combined with conventional EPR measurements of the librational
      amplitude, shows that torsional fluctuations of the peptide backbone take place
      on the subnanosecond to nanosecond timescale, with little temperature dependence.
      Associated fluctuations in polar fields from the peptide could facilitate ion
      permeation.

PMID- 18096633
TI  - Molecular dynamics simulations of hemoglobin A in different states and bound to
      DPG: effector-linked perturbation of tertiary conformations and HbA concerted
      dynamics.
AB  - Recent functional studies reported on human adult hemoglobin (HbA) show that
      heterotropic effector-linked tertiary structural changes are primarily
      responsible for modulating the oxygen affinity of hemoglobin. We present the
      results of 6-ns molecular dynamics simulations performed to gain insights into
      the dynamical and structural details of these effector-linked tertiary changes.
      All-atom simulations were carried out on a series of models generated for T- and
      R-state HbA, and for 2,3-diphosphoglycerate-bound models. Cross-correlation
      analyses identify both intra- and intersubunit correlated motions that are
      perturbed by the presence of the effector. Principal components analysis was used
      to decompose the covariance matrix extracted from the simulations and reconstruct
      the trajectories along the principal coordinates representative of functionally
      important collective motions. It is found that HbA in both quaternary states
      exists as ensembles of tertiary conformations that introduce dynamic
      heterogeneity in the protein. 2,3-Diphosphoglycerate induces significant
      perturbations in the fluctuations of both HbA states that translate into the
      protein visiting different tertiary conformations within each quaternary state.
      The analysis reveals that the presence of the effector affects the most important
      components of HbA motions and that heterotropic effectors modify the overall
      dynamics of the quaternary equilibrium via tertiary changes occurring in regions
      where conserved functionally significant residues are located, namely in the loop
      regions between helices C and E, E and F, and F and G, and in concerted helix
      motions. The changes are not apparent when comparing the available x-ray crystal
      structures in the presence and absence of effector, but are striking when
      comparing the respective dynamic tertiary conformations of the R and T tetramers.

PMID- 18096634
TI  - Breakdown of the endothelial barrier function in tumor cell transmigration.
AB  - The ability of tumor cells to metastasize is associated with a poor prognosis for
      cancer. During the process of metastasis, tumor cells circulating in the blood or
      lymph vessels can adhere to, and potentially transmigrate through, the
      endothelium and invade the connective tissue. We studied the effectiveness of the
      endothelium as a barrier against the invasion of 51 tumor cell lines into a three
      dimensional collagen matrix. Only nine tumor cell lines showed attenuated
      invasion in the presence of an endothelial cell monolayer, whereas 17 cell lines
      became invasive or showed a significantly increased invasion. Endothelial cells
      cocultured with invasive tumor cells increased chemokine gene expression of IL-8
      and Gro-beta. Expression of the IL-8 and Gro-beta receptor, CXCR2, was
      upregulated in invasive tumor cells. Addition of IL-8 or Gro-beta increased tumor
      cell invasiveness by more than twofold. Tumor cell variants selected for high
      CXCR2 expression were fourfold more invasive in the presence of an endothelial
      cell layer, whereas CXCR2 siRNA knock-down cells were fivefold less invasive. We
      demonstrate that Gro-beta and IL-8 secreted by endothelial cells, together with
      CXCR2 receptor expression on invasive tumor cells, contribute to the breakdown of
      the endothelial barrier by enhancing tumor cell force generation and cytoskeletal
      remodeling dynamics.

PMID- 18096635
TI  - Endoscopic ultrasound in cancer staging.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) represents one of the most significant
      developments in endoscopy over the past 20 years. It allows highly detailed
      assessment of the gastrointestinal wall layers as well as to visualize
      extraluminal structures such as the mediastium and retroperitoneum. METHODS: The
      literature was reviewed to assess the role of EUS in cancer staging. RESULTS: EUS
      is an integral part of the staging of many upper gastrointestinal cancers as well
      as rectal and lung cancer and has been shown to be cost-effective. It can be used
      to confirm malignancy in suspicious lesions as well as to identify and confirm
      nodal or metastatic spread. It has been used to re-stage cancers following
      chemoradiotherapy, but results are disappointing. Future developments are
      discussed, which may include using EUS-guided delivery of anti-tumour agents
      directly into tumours.

PMID- 18096636
TI  - The biochemistry and biology of extracellular plant lipid-transfer proteins
      (LTPs).
AB  - Plant lipid-transfer proteins (LTPs) are abundant, small, lipid binding proteins
      that are capable of exchanging lipids between membranes in vitro. Despite their
      name, a role in intracellular lipid transport is considered unlikely, based on
      their extracellular localization. A number of other biological roles, including
      antimicrobial defense, signaling, and cell wall loosening, have been proposed,
      but conclusive evidence is generally lacking, and these functions are not well
      correlated with in vitro activity or structure. A survey of sequenced plant
      genomes suggests that the two biochemically characterized families of LTPs are
      phylogenetically restricted to seed plants and are present as substantial gene
      families. This review aims to summarize the current understanding of LTP
      biochemistry, as well as the evidence supporting the proposed in vivo roles of
      these proteins within the emerging post-genomic framework.

PMID- 18096637
TI  - Buried water molecules in helical transmembrane proteins.
AB  - Buried water molecules (having no contact with bulk solvent) in 30 helical
      transmembrane (TM) protein structures were identified. The average amount of
      buried water in helical TM proteins is about the same as for all water-soluble
      (WS) proteins, but it is greater than the average for helical WS proteins. Buried
      waters in TM proteins make more polar contacts, and are more frequently found
      contacting helices than in WS proteins. The distribution of the buried water
      binding sites across the membrane profile shows that the sites to some extent
      reflect protein function. There is also evidence for asymmetry of the sites, with
      more in the extracellular half of the membrane. Many of the buried water contact
      sites are conserved across families of proteins, including family members having
      different functions. This suggests that at least some buried waters play a role
      in structural stabilization. Disease-causing mutations, which are known to result
      in misfolded TM proteins, occur at buried water contact sites at a higher than
      random frequency, which also supports a stabilizing role for buried water
      molecules.

PMID- 18096638
TI  - Solution structure of the C-terminal domain of Ole e 9, a major allergen of olive
      pollen.
AB  - Ole e 9 is an olive pollen allergen belonging to group 2 of pathogenesis-related
      proteins. The protein is composed of two immunological independent domains: an N
      terminal domain (NtD) with 1,3-beta-glucanase activity, and a C-terminal domain
      (CtD) that binds 1,3-beta-glucans. We have determined the three-dimensional
      structure of CtD-Ole e 9 (101 amino acids), which consists of two parallel alpha
      helices forming an angle of approximately 55 degrees , a small antiparallel beta
      sheet with two short strands, and a 3-10 helix turn, all connected by long coil
      segments, resembling a novel type of folding among allergens. Two regions
      surrounded by aromatic residues (F49, Y60, F96, Y91 and Y31, H68, Y65, F78) have
      been localized on the protein surface, and a role for sugar binding is suggested.
      The epitope mapping of CtD-Ole e 9 shows that B-cell epitopes are mainly located
      on loops, although some of them are contained in secondary structural elements.
      Interestingly, the IgG and IgE epitopes are contiguous or overlapped, rather than
      coincident. The three-dimensional structure of CtD-Ole e 9 might help to
      understand the underlying mechanism of its biochemical function and to determine
      possible structure-allergenicity relationships.

PMID- 18096639
TI  - Unique fluorophores in the dimeric archaeal histones hMfB and hPyA1 reveal the
      impact of nonnative structure in a monomeric kinetic intermediate.
AB  - Homodimeric archaeal histones and heterodimeric eukaryotic histones share a
      conserved structure but fold through different kinetic mechanisms, with a
      correlation between faster folding/association rates and the population of
      kinetic intermediates. Wild-type hMfB (from Methanothermus fervidus) has no
      intrinsic fluorophores; Met35, which is Tyr in hyperthermophilic archaeal
      histones such as hPyA1 (from Pyrococcus strain GB-3A), was mutated to Tyr and
      Trp. Two Tyr-to-Trp mutants of hPyA1 were also characterized. All fluorophores
      were introduced into the long, central alpha-helix of the histone fold. Far-UV
      circular dichroism (CD) indicated that the fluorophores did not significantly
      alter the helical content of the histones. The equilibrium unfolding transitions
      of the histone variants were two-state, reversible processes, with DeltaG degrees
      (H2O) values within 1 kcal/mol of the wild-type dimers. The hPyA1 Trp variants
      fold by two-state kinetic mechanisms like wild-type hPyA1, but with increased
      folding and unfolding rates, suggesting that the mutated residues (Tyr-32 and Tyr
      36) contribute to transition state structure. Like wild-type hMfB, M35Y and M35W
      hMfB fold by a three-state mechanism, with a stopped-flow CD burst-phase
      monomeric intermediate. The M35 mutants populate monomeric intermediates with
      increased secondary structure and stability but exhibit decreased folding rates;
      this suggests that nonnative interactions occur from burial of the hydrophobic
      Tyr and Trp residues in this kinetic intermediate. These results implicate the
      long central helix as a key component of the structure in the kinetic monomeric
      intermediates of hMfB as well as the dimerization transition state in the folding
      of hPyA1.

PMID- 18096640
TI  - Enhanced performance in prediction of protein active sites with THEMATICS and
      support vector machines.
AB  - Theoretical microscopic titration curves (THEMATICS) is a computational method
      for the identification of active sites in proteins through deviations in computed
      titration behavior of ionizable residues. While the sensitivity to catalytic
      sites is high, the previously reported sensitivity to catalytic residues was not
      as high, about 50%. Here THEMATICS is combined with support vector machines (SVM)
      to improve sensitivity for catalytic residue prediction from protein 3D structure
      alone. For a test set of 64 proteins taken from the Catalytic Site Atlas (CSA),
      the average recall rate for annotated catalytic residues is 61%; good precision
      is maintained selecting only 4% of all residues. The average false positive rate,
      using the CSA annotations is only 3.2%, far lower than other 3D-structure-based
      methods. THEMATICS-SVM returns higher precision, lower false positive rate, and
      better overall performance, compared with other 3D-structure-based methods.
      Comparison is also made with the latest machine learning methods that are based
      on both sequence alignments and 3D structures. For annotated sets of well
      characterized enzymes, THEMATICS-SVM performance compares very favorably with
      methods that utilize sequence homology. However, since THEMATICS depends only on
      the 3D structure of the query protein, no decline in performance is expected when
      applied to novel folds, proteins with few sequence homologues, or even orphan
      sequences. An extension of the method to predict non-ionizable catalytic residues
      is also presented. THEMATICS-SVM predicts a local network of ionizable residues
      with strong interactions between protonation events; this appears to be a special
      feature of enzyme active sites.

PMID- 18096641
TI  - LTHREADER: prediction of extracellular ligand-receptor interactions in cytokines
      using localized threading.
AB  - Identification of extracellular ligand-receptor interactions is important for
      drug design and the treatment of diseases. Difficulties in detecting these
      interactions using high-throughput experimental techniques motivate the
      development of computational prediction methods. We propose a novel threading
      algorithm, LTHREADER, which generates accurate local sequence-structure interface
      alignments and integrates various statistical scores and experimental binding
      data to predict interactions within ligand-receptor families. LTHREADER uses a
      profile of secondary structure and solvent accessibility predictions with residue
      contact maps to guide and constrain alignments. Using a decision tree classifier
      and low-throughput experimental data for training, it combines information
      inferred from statistical interaction potentials, energy functions, correlated
      mutations, and conserved residue pairs to predict interactions. We apply our
      method to cytokines, which play a central role in the development of many
      diseases including cancer and inflammatory and autoimmune disorders. We tested
      our approach on two representative families from different structural classes
      (all-alpha and all-beta proteins) of cytokines. In comparison with the state-of
      the-art threader RAPTOR, LTHREADER generates on average 20% more accurate
      alignments of interacting residues. Furthermore, in cross-validation tests,
      LTHREADER correctly predicts experimentally confirmed interactions for a common
      binding mode within the 4-helical long-chain cytokine family with 75% sensitivity
      and 86% specificity with 40% gain in sensitivity compared to RAPTOR. For the TNF
      like family our method achieves 70% sensitivity with 55% specificity with 70%
      gain in sensitivity. LTHREADER combines information from multiple complex
      templates when such data are available. When only one solved structure is
      available, a localized PSI-BLAST approach also outperforms standard threading
      methods with 25%-50% improvements in sensitivity.

PMID- 18096642
TI  - Structural determinants of nitroxide motion in spin-labeled proteins: solvent
      exposed sites in helix B of T4 lysozyme.
AB  - Site-directed spin labeling provides a means for exploring structure and dynamics
      in proteins. To interpret the complex EPR spectra that often arise, it is
      necessary to characterize the rotamers of the spin-labeled side chain and the
      interactions they make with the local environment in proteins of known structure.
      For this purpose, crystal structures have been determined for T4 lysozyme bearing
      a nitroxide side chain (R1) at the solvent-exposed helical sites 41 and 44 in the
      B helix. These sites are of particular interest in that the corresponding EPR
      spectra reveal two dynamic states of R1, one of which is relatively immobilized
      suggesting interactions of the nitroxide with the environment. The crystal
      structures together with the effect of mutagenesis of nearest neighbors on the
      motion of R1 suggest intrahelical interactions of 41R1 with the i + 4 residue and
      of 44R1 with the i + 1 residue. Such interactions appear to be specific to
      particular rotamers of the R1 side chain.

PMID- 18096643
TI  - An unusual red-edge excitation and time-dependent Stokes shift in the single
      tryptophan mutant protein DD-carboxypeptidase from Streptomyces: the role of
      dynamics and tryptophan rotamers.
AB  - The fluorescence emission of the single tryptophan (W233) of the mutant protein
      DD-carboxypeptidase from streptomyces is characterized by a red-edge excitation
      shift (REES), i.e., the phenomenon that the wavelength of maximum emission
      depends on the excitation wavelength. This phenomenon is an indication for a
      strongly reduced dynamic environment of the single tryptophan, which has a very
      low accessibility to the solvent. The REES shows, however, an unusual temperature
      and time dependence. This, together with the fluorescence lifetime analysis,
      showing three resolvable lifetimes, can be explained by the presence of three
      rotameric states that can be identified using the Dead-End Elimination method.
      The three individual lifetimes increase with increasing emission wavelength,
      indicating the presence of restricted protein dynamics within the rotameric
      states. This is confirmed by time-resolved anisotropy measurements that show
      dynamics within the rotamers but not among the rotamers. The global picture is
      that of a protein with a single buried tryptophan showing strongly restricted
      dynamics within three distinct rotameric states with different emission spectra
      and an anisotropic environment.

PMID- 18096644
TI  - Characterizing the Mycobacterium tuberculosis Rv2707 protein and determining its
      sequences which specifically bind to two human cell lines.
AB  - The Rv2707 gene encoding a putative alanine- and leucine-rich protein was found
      to be present in all Mycobacterium tuberculosis complex strains (by PCR) and its
      transcription was shown by RT-PCR in all but M. bovis and M. microti. Antibodies
      raised against Rv2707 peptides specifically recognized the native protein by
      Western blot and were able to locate this protein on the M. tuberculosis membrane
      by immunoelectron microscopy. A549 and U937 cells lines were used in binding
      assays involving synthetic peptides covering the whole Rv2707 protein. High A549
      cell-binding peptide 16083 (281 QEEWPAPATHAHRLGNWLKAY 300) was identified.
      Peptides 16072 (61 LFGPDTLPAIEKSALSTAHSY 80) and 16084 (301 RIGVGTTTYSSTAQHSAVAA
      320) presented high specific binding to both A549 and U937 cells. Cross-linking
      assays revealed that peptide 16084 specifically bound to a 40-kDa and a 50-kDa
      U937 cell membrane protein. High activity binding peptides (HABPs) 16083 and
      16084 were able to inhibit M. tuberculosis invasion of A549 cells. Our results
      suggest that these sequences could be part of the binding sites used by the
      bacillus for interacting with target cells, and thus represent good candidates to
      be tested in a future subunit-based, multiepitope, antituberculosis vaccine.

PMID- 18096645
TI  - Estimating the length of transmembrane helices using Z-coordinate predictions.
AB  - Zpred2 is an improved version of ZPRED, a predictor for the Z-coordinates of
      alpha-helical membrane proteins, that is, the distance of the residues from the
      center of the membrane. Using principal component analysis and a set of neural
      networks, Zpred2 analyzes data extracted from the amino acid sequence, the
      predicted topology, and evolutionary profiles. Zpred2 achieves an average
      accuracy error of 2.18 A (2.17 A when an independent test set is used), an
      improvement by 15% compared to the previous version. We show that this accuracy
      is sufficient to enable the predictions of helix lengths with a correlation
      coefficient of 0.41. As a comparison, two state-of-the-art HMM-based topology
      prediction methods manage to predict the helix lengths with a correlation
      coefficient of less than 0.1. In addition, we applied Zpred2 to two other
      problems, the re-entrant region identification and model validation. Re-entrants
      were able to be detected with a certain consistency, but not better than with
      previous approaches, while incorrect models as well as mispredicted helices of
      transmembrane proteins could be distinguished based on the Z-coordinate
      predictions.

PMID- 18096646
TI  - Youth sexual behaviour in a boomtown: implications for the control of sexually
      transmitted infections.
AB  - BACKGROUND: Northeastern British Columbia, Canada, is undergoing rapid in
      migration of young, primarily male, workers in response to the "boom" in the
      oil/gas industries. Chlamydia rates in the region exceed the provincial average
      by 32% (294.6 cases per 100 000 persons compared with 213.3). Evidence indicates
      that sociocultural and structural determinants of young people's sexual health
      are key to consider in the design of interventions. OBJECTIVES: To investigate
      how sociocultural and structural features related to the oil/gas boom are
      perceived to affect the sexual behaviour of youth in a Northeastern "boomtown".
      METHODS: The study included ethnographic fieldwork (8 weeks) and in-depth
      interviews with 25 youth (ages 15-25 years) and 14 health/social service
      providers. RESULTS: Participants identified four main ways in which the
      sociocultural and structural conditions created by the boom affect sexual
      behaviours, fuelling the spread of sexually transmitted infections (STIs):
      mobility of oil/gas workers; binge partying; high levels of disposable income and
      gendered power dynamics. CONCLUSIONS: The sociocultural and structural conditions
      that are fostered by a resource-extraction boom appear to exacerbate sexual
      health inequalities among youths who live and work in these rapidly urbanising,
      remote locales. To meet the needs of this population, we recommend STI prevention
      and testing service delivery models that incorporate STI testing outreach to
      oil/gas workers and condom distribution. Global, national and local STI control
      efforts should consider the realities and needs of similar subpopulations of
      young people.

PMID- 18096647
TI  - Sexual and demographic determinants for herpes simplex virus type 2 among
      fishermen along Lake Victoria, Kenya.
AB  - OBJECTIVES: To determine the prevalence and correlates of herpes simplex virus
      type 2 (HSV-2) seropositivity among fishermen along the shores of Lake Victoria
      in Kisumu district, Kenya. METHODS: Sera from a random sample of 250 fishermen
      from 18 beaches were collected after a detailed sociodemographic interview. HSV-2
      infection was tested by Kalon HSV-2 ELISA. RESULTS: The HSV-2 seroprevalence was
      63.9%. In multivariate analysis, fishermen were more likely to be infected with
      HSV-2 if they were HIV positive (prevalence ratio (PR) 1.27; 95% CI 1.06 to 1.52)
      compared with those testing HIV negative, were aged 18-20 (PR 0.49; 95% CI 0.24
      to 0.99) and older than 40 (PR 1.66; 95% CI 1.30 to 2.14) years compared with
      those aged 21-25 years, perceived their last two sexual partners to have a
      sexually transmitted infection (STI; PR 1.27; 95% CI 1.06 to 1.52) compared with
      those who did not and were more likely to be circumcised (PR 1.49; 95% CI 1.19 to
      1.86). CONCLUSIONS: HSV-2 seroprevalence is high among this population and is
      associated with HIV serostatus, age, perception about partner's STI status and
      circumcision.

PMID- 18096648
TI  - Relations between sexually transmitted infection diagnosis and sexual
      compulsivity in a community-based sample of men who have sex with men.
AB  - OBJECTIVE: To assess relations between sexual compulsivity and a history of
      sexually transmitted infection (STI) diagnosis and testing among a community
      based sample of men who have sex with men (MSM) in a mid-size urban area of the
      midwestern United States. METHODS: Sexual health data were collected from 504 MSM
      in the metropolitan area of Indianapolis, Indiana, using a community-based
      participatory research approach. Sexual compulsivity scores were assessed using
      the Sexual Compulsivity Scale (SCS). RESULTS: The reliability and construct
      validity of the SCS were determined to be high in the total study sample. Men who
      scored high on the SCS reported higher levels of sexual risk behaviour with both
      male and female partners and were significantly more likely to have been
      diagnosed with STI (including chlamydia, gonorrhoea, both hepatitis A and B, and
      syphilis) than other men. Men who scored high on the SCS were not more likely
      than other men to have been tested for STI, despite higher levels of sexual risk.
      CONCLUSIONS: The SCS may be useful as a supplemental instrument in public health
      programmes and healthcare settings that encourage men to assess their sexual
      behaviours and make decisions to pursue STI or HIV screening. For those already
      diagnosed with an STI, the SCS may help providers to identify the cognitive and
      affective components of sexual behaviours that increase the likelihood that an
      STI will be transmitted to a sexual partner.

PMID- 18096649
TI  - National study of HIV testing in men who have sex with men attending
      genitourinary clinics in the United Kingdom.
AB  - OBJECTIVES: To determine what proportion of men who have sex with men (MSM)
      attending genitourinary medicine (GUM) clinics are offered and accept an HIV test
      and to examine clinic and patient characteristics associated with offer and
      uptake. METHODS: A cross-sectional study of all GUM clinics in the United
      Kingdom, involving a case note review of up to 30 patient records per clinic and
      the completion of a clinic policy form. RESULTS: Overall, 86% of MSM were offered
      a test and of those 82% accepted a test. Attending with symptoms of a sexually
      transmitted infection (STI), fewer numbers of partners in the past three months
      and having tested previously were all independently associated with a decreased
      likelihood of being offered a test. Attending with symptoms of an STI, increasing
      age, never having had a risk from unprotected anal intercourse or a previous HIV
      test and increasing time to wait for results were all independently associated
      with a decreased likelihood of a patient accepting a test. Only a quarter of
      clinics reported a written policy for HIV testing intervals among MSM; however,
      all clinics reported offering testing to all new MSM patients at first screening.
      The testing policy for re-attending patients was less clear. CONCLUSIONS: Testing
      must reach those at most risk and those less likely to test in order to reduce
      further the proportion of undiagnosed HIV infection. This study suggests that
      opportunities to detect infection may be being missed and a move towards
      universal testing of all MSM attending with a new episode, as well as testing
      within the window period, is recommended.

PMID- 18096650
TI  - Movement training advances the emergence of reaching in infants born at less than
      33 weeks of gestational age: a randomized clinical trial.
AB  - BACKGROUND AND PURPOSE: This study had 2 purposes: (1) to compare the emergence
      of reaching in infants born full-term and infants born at less than 33 weeks of
      gestational age and (2) to evaluate the effectiveness of a movement training
      program on the emergence of reaching in this preterm population. PARTICIPANTS:
      Twenty-six infants born at less than 33 weeks of gestational age and with a birth
      weight less than 2,500 g were randomly assigned to receive 20 minutes of daily
      movement training (PT-M group) or daily social training (PT-S group) and were
      compared with 13 infants born full-term (FT-S group). METHODS: Reaching and hand
      object interactions were tested every other week for 8 weeks. At each visit,
      infants were allowed six 30-second opportunities to contact a midline toy.
      RESULTS: The FT-S and PT-M groups reached earlier and more consistently than the
      PT-S group. Specifically, the subjects in the FT-S group contacted the toy for
      longer durations and with an open, ventral surface of their hand. The PT-M group
      demonstrated increases in the number of hand-object contacts, the number of
      consistent reaches, and the percentage of time interacting with the toy and the
      surface of hand-object contact. DISCUSSION AND CONCLUSION: This project
      demonstrates that there are early gross motor skill differences in infants born
      at less than 33 weeks of gestational age. A caregiver-based daily training
      program, however, is effective at lessening some, but not all, of these
      differences over the short term.

PMID- 18096651
TI  - Multidimensional motor sequence learning is impaired in older but not younger or
      middle-aged adults.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to identify which
      characteristics of a multidimensional sequence containing motor, spatial, and
      temporal elements would be most salient for motor sequence learning and whether
      age might differentially affect this learning. SUBJECTS: Younger (n=11, mean
      age=26.0 years), middle-aged (n=13, mean age=50.7 years), and older (n=11, mean
      age=77.5 years) adults who were neurologically intact participated in the study.
      METHODS: Participants practiced a sequencing task with repeated motor, spatial,
      and temporal dimensions for 2 days; on a separate third day, participants
      completed retention and interference tests designed to assess sequence learning
      and which elements of the sequence were learned. The mean median response time
      for each block of responses was used to assess motor sequence learning. RESULTS:
      Younger and middle-aged adults demonstrated sequence-specific motor learning at
      retention testing via faster response times for repeated sequences than random
      sequences; both of these groups showed interference for the motor dimension. In
      contrast, older adults demonstrated nonspecific learning (ie, similar
      improvements in response time for both random and repeated sequences). These
      findings were shown by a lack of difference between random and repeated sequence
      performance in the older adult group both at retention testing and during
      interference tests. CONCLUSION AND DISCUSSION: Our data suggest that, when
      younger and middle-aged adults practice sequences containing multiple dimensions
      of movement, the motor element is most important for motor learning. The absence
      of sequence-specific change demonstrated by an older adult group that was healthy
      suggests an age-related impairment in motor learning that may have profound
      implications for rehabilitation.

PMID- 18096652
TI  - Journal publication productivity in academic physical therapy programs in the
      United States and Puerto Rico from 1998 to 2002.
AB  - BACKGROUND AND PURPOSE: The peer-reviewed journal article is the basic unit by
      which scholarship is defined. Few studies have examined peer-reviewed publication
      productivity in academic physical therapy programs. In this study, the
      publication productivity in academic physical therapy programs in the United
      States and Puerto Rico from 1998 to 2002 was documented, and publication
      productivity was examined in the context of selected program characteristics.
      SUBJECTS AND METHODS: A total of 194 programs listed on the Commission on
      Accreditation in Physical Therapy Education (CAPTE) Web site in the spring of
      2004 were examined. The databases were searched for bibliographic citations of
      journal articles attributed to particular programs. The program characteristics
      of faculty size, offering of a research doctorate, and listing in the Carnegie
      Classification of Institutions of Higher Education (Carnegie Classification) were
      compared with the number of citations. RESULTS: A total of 169 programs had at
      least 1 attributed citation, 50.3% of the programs had fewer than 5 citations,
      and 3% had 44 or more citations. Rankings based on the number of citations
      changed when adjusted for faculty size. Of the 38 programs offering a research
      doctoral degree, 16 had 20 or more citations. Five programs with 44 or more
      citations were all categorized by the Carnegie Classification as doctoral
      intensive or extensive. DISCUSSION AND CONCLUSION: A few programs had a large
      number of attributed bibliographic citations, but the majority of programs had
      limited publication productivity in the 5 years studied. These results may
      provide a baseline for studying the effectiveness of the relatively new CAPTE
      standards mandating scholarship by physical therapy faculty over time and the
      impact of the Doctor of Physical Therapy degree on research in physical therapy.

PMID- 18096653
TI  - An epidemiological study of the role of chrysotile asbestos fibre dimensions in
      determining respiratory disease risk in exposed workers.
AB  - BACKGROUND: Evidence from toxicological studies indicates that the risk of
      respiratory diseases varies with asbestos fibre length and width. However, there
      is a total lack of epidemiological evidence concerning this question. METHODS:
      Data were obtained from a cohort mortality study of 3072 workers from an asbestos
      textile plant which was recently updated for vital status through 2001. A
      previously developed job exposure matrix based on phase contrast microscopy (PCM)
      was modified to provide fibre size-specific exposure estimates using data from a
      re-analysis of samples by transmission electron microscopy (TEM). Cox
      proportional hazards models were fit using alternative exposure metrics for
      single and multiple combinations of fibre length and diameter. RESULTS: TEM-based
      cumulative exposure estimates were found to provide stronger predictions of
      asbestosis and lung cancer mortality than PCM-based estimates. Cumulative
      exposures based on individual fibre size-specific categories were all found to be
      highly statistically significant predictors of lung cancer and asbestosis. Both
      lung cancer and asbestosis were most strongly associated with exposure to thin
      fibres (<0.25 microm). Longer (>10 microm) fibres were found to be the strongest
      predictors of lung cancer, but an inconsistent pattern with fibre length was
      observed for asbestosis. Cumulative exposures were highly correlated across all
      fibre size categories in this cohort (0.28-0.99, p values <0.001), which
      complicates the interpretation of the study findings. CONCLUSIONS: Asbestos fibre
      dimension appears to be an important determinant of respiratory disease risk.
      Current PCM-based methods may underestimate asbestos exposures to the thinnest
      fibres, which were the strongest predictor of lung cancer or asbestosis mortality
      in this study. Additional studies are needed of other asbestos cohorts to further
      elucidate the role of fibre dimension and type.

PMID- 18096654
TI  - Mortality risk in the French cohort of uranium miners: extended follow-up 1946
      1999.
AB  - OBJECTIVES: This paper presents the risk of death from lung cancer and from other
      causes of death for the French cohort of uranium miners through 1999 and
      estimates associations with radon exposure. METHODS: The cohort includes men
      employed as uranium miners for at least 1 year between 1946 and 1990. For each
      miner, vital status and cause of death were obtained from the national registry,
      and radon exposure was reconstructed for each year. Standardised mortality ratios
      were computed with national mortality rates as references. Exposure-risk
      relationships were estimated by Poisson regression, with a linear excess relative
      risk (ERR) model and a 5-year lag. RESULTS: The cohort included 5086 miners and
      153 063 person-years of exposure. The mean duration of follow-up was 30.1 years.
      In all 4140 miners exposed to radon, the average cumulative exposure was 36.6
      working level months (WLM). There were 1411 deaths of miners <85 years of age.
      The miners did not differ significantly in overall mortality from the general
      male population. The analysis confirmed an excess risk of lung cancer death (n =
      159; SMR = 1.43; 95% CI: 1.22 to 1.68), which increased significantly with
      cumulative radon exposure (ERR per 100 WLM = 0.71; 95% CI: 0.29 to 1.35). The ERR
      per unit exposure was much higher after 1955, when the accuracy of exposure
      measurement improved substantially (ERR per 100 WLM = 2.00; 95% CI: 0.91 to
      3.65). A significant excess of kidney cancer deaths was observed (n = 20; SMR =
      2.0; 95% CI: 1.22 to 3.09), which was not associated with cumulative radon
      exposure. No excess was observed for other causes of death, except silicosis (n =
      23; SMR = 7.12; 95% CI: 4.51 to 10.69). CONCLUSIONS: The analysis confirmed the
      excess risk of death from lung cancer associated with low radon exposure. An
      excess risk of death from kidney cancer was also observed, apparently not
      associated with cumulative radon exposure.

PMID- 18096655
TI  - Estimating reduction in occupational disease burden following reduction in
      exposure.
AB  - BACKGROUND/OBJECTIVE: Many occupational exposures causing disease cannot feasibly
      be eliminated entirely, but policies that reduce the exposures may be under
      consideration. This paper sets out to clarify how to estimate the reduction in
      occupational disease following a reduction in exposure, and shows a real-data
      illustration for doing this. METHODS: Modest extensions of standard expressions
      for attributable fractions permit estimation of fractions by which cases would be
      reduced by policies that do not eliminate exposure but change exposure
      distributions. However, this requires information on the exposure-response
      relation and on distribution of exposures. RESULTS: From hypothetical scenarios
      and a real example this paper explores how attributable cases are distributed by
      exposure level and, in particular, the proportion by which attributable cancers
      are reduced by eliminating exposures above a limit (the classic occupational
      limit regulation). It shows how this depends on the shape of the exposure
      response relation and to some extent the shape of the exposure distribution, as
      well as on the proportion exposed above the limit. For linear no-threshold
      relations and left-skewed exposure distributions, the majority of the burden may
      be in a large number of people experiencing small relative risks, and thus may
      not be tackled by a strategy to reduce exposures above a certain limit.
      CONCLUSION: With appropriate data, estimating the disease burden in terms of the
      distribution of exposure is straightforward and can help to clarify the likely
      outcome of an intervention.

PMID- 18096656
TI  - The occupational risk of Helicobacter pylori infection among workers in
      institutions for people with intellectual disability.
AB  - OBJECTIVES: A cross-sectional study to evaluate the occupational risk for
      Helicobacter pylori infection, on top of other risk factors, in staff members of
      institutions for people with intellectual disability. In these institutions, the
      residents had a documented high prevalence of H pylori infection (86% presenting
      antibodies). As a control group, the study used administrative workers from other
      companies. METHODS: All participants completed a questionnaire concerning
      sociodemographic characteristics, medical history and employment data and they
      underwent a serology test. RESULTS: 671 staff members of the institutions and 439
      subjects in the control group participated in the study. Prevalence of H pylori
      antibodies was significantly higher in the study group than in the control group
      (40.6% vs 29.2%; p<0.001). Crude odds ratio for occupational risk was 1.68;
      adjusting for the confounding effect of age, gender, body mass index, smoking,
      tropical journeys and number of household members during childhood resulted in an
      even higher (adjusted) OR of 1.98 (95% CI 1.42 to 2.69). In multiple logistic
      regression analysis adjusting for variables shown to be confounders, faecal
      contact continued to be significantly associated with H pylori infection.
      Attributable risk was 49.5%. CONCLUSIONS: H pylori infection is an occupational
      risk in healthcare workers working in institutions for people with intellectual
      disability. We identified faecal contact as an independent occupational risk
      factor for H pylori infection.

PMID- 18096657
TI  - Leptin-mediated hypothalamic pathway of cholecystokinin (CCK-8) to regulate body
      weight in free-feeding rats.
AB  - Regulation of body weight (BW) results from the interplay between different
      hormonal systems acting at central and peripheral level. This study aims at
      characterizing the involvement of cholecystokinin (CCK) in BW and energy balance
      regulation. We have characterized, in free-feeding rats, the effect of CCK-8 on
      1) food intake, BW, and adiposity; 2) skeletal muscle metabolism; 3) leptin
      signaling pathway within the arcuate nucleus of the hypothalamus; and 4) the
      permeability of brain barriers to leptin. We demonstrate here that CCK-8 acutely
      decreases BW by a mechanism partially dependent on central leptin pathways, based
      on the following results: 1) the effect of CCK was less intense in rats lacking
      functional leptin receptors (Zucker fa/fa), 2) CCK-8 facilitated the uptake of
      leptin from peripheral circulation to cerebrospinal fluid (CSF), 3) the
      concentration of leptin in CSF of rats receiving CCK was more elevated in those
      animals showing higher loss of BW, and 4) CCK activated leptin signaling pathways
      within the hypothalamus as well as phosphorylation of AMP-activated protein
      kinase in skeletal muscle. We also suggest that gain of BW may be linked to
      individual susceptibility to the effect of CCK, because we observed that in
      animals treated with this hormone, the increase of BW negatively correlated with
      leptin concentration within the CSF. Our data show that CCK has a negative impact
      on energy balance and suggest that CCK facilitates the access of leptin to
      hypothalamic areas, thus allowing leptin to act on hypothalamic targets involved
      in BW control.

PMID- 18096659
TI  - Discovery of a functional glucocorticoid receptor beta-isoform in zebrafish.
AB  - In humans, two glucocorticoid receptor (GR) splice variants exist: GRalpha and
      GRbeta, which are identical between amino acids 1-727 and then diverge. Whereas
      GRalpha (the canonical GR) acts as a ligand-activated transcription factor,
      GRbeta does not bind traditional glucocorticoid agonists, lacks GRalpha's
      transactivational activity, and acts as a dominant-negative inhibitor of GRalpha.
      It has been suggested that this receptor isoform is involved in the induction of
      glucocorticoid resistance in asthma patients. Unfortunately, a GR beta-isoform
      has been detected in only humans, and therefore, an animal model for studies on
      this isoform is lacking. In the present study, we demonstrate that in zebrafish a
      GR isoform exists that diverges from the canonical zebrafish GR at the same
      position as human GRbeta from human GRalpha. The zebrafish GR beta-isoform acts
      as a dominant-negative inhibitor in reporter assays, and the extent of inhibition
      and the effective GRalpha/GRbeta ratio is similar to studies performed with the
      human GR isoforms. In addition, the subcellular localization of zebrafish GRbeta
      is similar to its human equivalent. Finally, expression levels of GRalpha and
      GRbeta were determined in adult zebrafish tissues and at several developmental
      stages. Both receptor isoforms were detected throughout the body, and GRbeta mRNA
      levels were relatively low compared with GRalpha mRNA levels, as in humans. Thus,
      for the first time, a GR beta-isoform has been identified in a nonhuman animal
      species, shedding new light on the relevance of this GR splice variant and
      providing a versatile animal model for studies on the GR system.

PMID- 18096658
TI  - Long-term, homologous prolactin, administered through ectopic pituitary grafts,
      induces hypothalamic dopamine neuron differentiation in adult Snell dwarf mice.
AB  - Pituitary prolactin (PRL) secretion is inhibited by dopamine (DA) released into
      the portal circulation from hypothalamic tuberoinfundibular DA (TIDA) neurons.
      Ames (df/df) and Snell (dw/dw) dwarf mice lack PRL, GH, and TSH, abrogating
      feedback and resulting in a reduced hypophysiotropic TIDA population. In Ames
      df/df, ovine PRL administration for 30 d during early postnatal development
      increases the TIDA neuron number to normal, but 30 d PRL treatment of adult df/df
      does not. The present study investigated the effects of homologous PRL,
      administered via renal capsule pituitary graft surgery for 4 or 6 months, on
      hypothalamic DA neurons in adult Snell dw/dw mice using catecholamine
      histofluorescence, tyrosine hydroxylase immunocytochemistry, and
      bromodeoxyuridine immunocytochemistry. PRL treatment did not affect TIDA neuron
      number in normal mice, but 4- and 6-month PRL-treated dw/dw had significantly
      increased (P < or = 0.01) TIDA (area A12) neurons compared with untreated dw/dw.
      Snell dwarfs treated with PRL for 6 months had more (P < or = 0.01) TIDA neurons
      than 4-month PRL-treated dw/dw, but lower (P < or = 0.01) numbers than normal
      mice. Periventricular nucleus (area A14) neuron number was lower in dwarfs than
      in normal mice, regardless of treatment. Zona incerta (area A13) neuron number
      was unchanged among phenotypes and treatments. Prolactin was unable to induce
      differentiation of a normal-sized A14 neuron population in dw/dw.
      Bromodeoxyuridine incorporation was lower (P < or = 0.01) in 6-month PRL-treated
      normal mice than in 6-month PRL-treated dwarfs in the subventricular zone of the
      lateral ventricle and in the dentate gyrus, and lower (P < or = 0.05) in 4-month
      untreated dwarfs than in 4-month untreated normal mice in the median eminence and
      the periventricular area surrounding the third ventricle. Thus, a PRL-sensitive
      TIDA neuron population exists in adult Snell dwarf mice when replacement uses
      homologous hormone and/or a longer duration. This finding indicates that there is
      potential for neuronal differentiation beyond early developmental periods and
      suggests plasticity within the mature hypothalamus.

PMID- 18096661
TI  - Is visfatin an adipokine or myokine? Evidence for greater visfatin expression in
      skeletal muscle than visceral fat in chickens.
AB  - Visfatin, an adipokine hormone produced primarily by visceral adipose tissue in
      mammals, has been implicated in the immune system, cellular aging, and glucose
      metabolism. Increased visceral adiposity and hyperglycemia have been correlated
      with elevated plasma visfatin levels in humans. The present study investigated
      visfatin cDNA and protein expression as well as plasma visfatin levels in
      chickens that are selected for rapid growth and are naturally hyperglycemic
      relative to mammals. By RT-PCR, we detected visfatin cDNA in multiple tissues in
      the chicken. The deduced amino acid sequence of full-length chicken visfatin was
      92-93% homologous to mammalian visfatin. Using real-time quantitative PCR and
      Western blotting, chicken skeletal muscle was found to contain 5- and 3-fold
      greater quantities of visfatin mRNA and protein than abdominal fat pad,
      respectively. Visfatin mRNA and protein quantities were not significantly
      different among sc and visceral adipose tissue depots. Skeletal muscle visfatin
      mRNA and protein quantities as well as plasma visfatin levels determined by
      enzyme immunoassay were significantly higher in 8-wk-old compared with 4-wk-old
      chickens, possibly due to rapid skeletal muscle growth and visceral fat accretion
      occurring in broiler chickens during this period. However, fasting and refeeding
      did not affect plasma visfatin levels in the chicken. Collectively, our results
      provide novel evidence that skeletal muscle, not the visceral adipose tissue, is
      the primary source of visfatin in chickens, thereby raising the possibility that
      visfatin may be acting as a myokine affecting skeletal muscle growth and
      metabolism.

PMID- 18096660
TI  - Phosphorylation state of tyrosine hydroxylase in the stalk-median eminence is
      decreased by progesterone in cycling female rats.
AB  - Progesterone has the capacity to suppress hypothalamic dopaminergic neuronal
      activity on proestrous afternoon and prolong or amplify the preovulatory
      prolactin surge in rats. In the present study, we examined enzyme activity and
      phosphorylation state of tyrosine hydroxylase (TH) in the stalk-median eminence
      of cycling female rats on proestrus and estrus and related these to circulating
      progesterone levels. Phospho-TH levels were evaluated by Western blot analysis.
      TH activity was determined from the rate of 3,4-dihydroxyphenylalanine (DOPA)
      accumulation. Phospho-TH levels at Ser-19, Ser-31, and Ser-40 were similar at
      1100, 1300, and 1500 h on proestrus but declined at 1700, 1900, and 2200 h,
      coincident with rising serum progesterone levels. Similarly, DOPA accumulation
      was 30-50% lower at 1700, 1900, and 2200 h as compared with 1100-1500 h on
      proestrus. Ser-31 and Ser-40 phosphorylation states were increased by 1100 h on
      estrus to a level similar to 1100 h on proestrus, whereas DOPA accumulation was
      30% greater on estrous as compared with proestrous morning. There were no
      significant differences among the several time points on proestrus and estrus
      with regard to TH protein or beta-tubulin levels. Exogenous progesterone
      administration (7.5 mg/kg, sc) before the preovulatory progesterone surge
      decreased TH activity and phospho-TH at Ser-19, Ser-31, and Ser-40, accompanied
      by premature increased serum prolactin. Our study suggests that decreased TH
      phosphorylation at Ser-19, Ser-31, and Ser-40 contributes to the decline in TH
      activity in the stalk-median eminence on proestrous afternoon and that
      progesterone may cause this initial cytoplasmic response of TH dephosphorylation.

PMID- 18096662
TI  - Adipose-specific disruption of signal transducer and activator of transcription 3
      increases body weight and adiposity.
AB  - To determine the role of STAT3 in adipose tissue, we used Cre-loxP DNA
      recombination to create mice with an adipocyte-specific disruption of the STAT3
      gene (ASKO mice). aP2-Cre-driven disappearance of STAT3 expression occurred on d
      6 of adipogenesis, a time point when preadipocytes have already undergone
      conversion to adipocytes. Thus, this knockout model examined the role of STAT3 in
      mature but not differentiating adipocytes. Beginning at 9 wk of age, ASKO mice
      weighed more than their littermate controls and had increased adipose tissue
      mass, associated with adipocyte hypertrophy, but not adipocyte hyperplasia,
      hyperphagia, or reduced energy expenditure. Leptin-induced, but not isoproterenol
      induced, lipolysis was impaired in ASKO adipocytes, which may partially explain
      the increased cell size. Despite reduced adiponectin and increased liver
      triacylglycerol, ASKO mice displayed normal glucose tolerance. Overall, these
      findings demonstrate that adipocyte STAT3 regulates body weight homeostasis in
      part through direct effects of leptin on adipocytes.

PMID- 18096664
TI  - The adipogenic acetyltransferase Tip60 targets activation function 1 of
      peroxisome proliferator-activated receptor gamma.
AB  - The transcription factor peroxisome proliferator-activated receptor gamma
      (PPARgamma) plays a key role in the regulation of lipid and glucose metabolism in
      adipocytes, by regulating their differentiation, maintenance, and function. The
      transcriptional activity of PPARgamma is dictated by the set of proteins with
      which this nuclear receptor interacts under specific conditions. Here we identify
      the HIV-1 Tat-interacting protein 60 (Tip60) as a novel positive regulator of
      PPARgamma transcriptional activity. Using tandem mass spectrometry, we found that
      PPARgamma and the acetyltransferase Tip60 interact in cells, and through use of
      chimeric proteins, we established that coactivation by Tip60 critically depends
      on the N-terminal activation function 1 of PPARgamma, a domain involved in
      isotype-specific gene expression and adipogenesis. Chromatin immunoprecipitation
      experiments showed that the endogenous Tip60 protein is recruited to PPARgamma
      target genes in mature 3T3-L1 adipocytes but not in preadipocytes, indicating
      that Tip60 requires PPARgamma for its recruitment to PPARgamma target genes.
      Importantly, we show that in common with disruption of PPARgamma function, small
      interfering RNA-mediated reduction of Tip60 protein impairs differentiation of
      3T3-L1 preadipocytes. Taken together, these findings qualify the
      acetyltransferase Tip60 as a novel adipogenic factor.

PMID- 18096663
TI  - Dopamine inhibits basal prolactin release in pituitary lactotrophs through
      pertussis toxin-sensitive and -insensitive signaling pathways.
AB  - Dopamine D2 receptors signal through the pertussis toxin (PTX)-sensitive G(i/o)
      and PTX-insensitive G(z) proteins, as well as through a G protein-independent,
      beta-arrestin/glycogen synthase kinase-3-dependent pathway. Activation of these
      receptors in pituitary lactotrophs leads to inhibition of prolactin (PRL)
      release. It has been suggested that this inhibition occurs through the G(i/o)
      alpha protein-mediated inhibition of cAMP production and/or G(i/o)-betagamma
      dimer-mediated activation of inward rectifier K(+) channels and inhibition of
      voltage-gated Ca(2+) channels. Here we show that the dopamine agonist-induced
      inhibition of spontaneous Ca(2+) influx and release of prestored PRL was
      preserved when cAMP levels were elevated by forskolin treatment. We further
      observed that dopamine agonists inhibited both spontaneous and depolarization
      induced Ca(2+) influx in untreated but not in PTX-treated cells. This inhibition
      was also observed in cells with blocked inward rectifier K(+) channels,
      suggesting that the dopamine effect on voltage-gated Ca(2+) channel gating is
      sufficient to inhibit spontaneous Ca(2+) influx. However, agonist-induced
      inhibition of PRL release was only partially relieved in PTX-treated cells,
      indicating that dopamine receptors also inhibit exocytosis downstream of voltage
      gated Ca(2+) influx. The PTX-insensitive step in agonist-induced inhibition of
      PRL release was not affected by the addition of wortmannin, an inhibitor of
      phosphatidylinositol 3-kinase, and lithium, an inhibitor of glycogen synthase
      kinase-3, but was attenuated in the presence of phorbol 12-myristate 13-acetate,
      which inhibits G(z) signaling pathway in a protein kinase C-dependent manner.
      Thus, dopamine inhibits basal PRL release by blocking voltage-gated Ca(2+) influx
      through the PTX-sensitive signaling pathway and by desensitizing Ca(2+) secretion
      coupling through the PTX-insensitive and protein kinase C-sensitive signaling
      pathway.

PMID- 18096665
TI  - Alterations in micro-ribonucleic acid expression profiles reveal a novel pathway
      for estrogen regulation.
AB  - Estrogens are steroid hormones that have been implicated in a variety of cellular
      and physiological processes in the development of diseases such as cancer and are
      also known to be associated with the effects of endocrine disrupting chemicals.
      Here we show that 17beta-estradiol (E(2)) alters microRNA (miRNA) expression
      profiles in the adult zebrafish (Danio rerio). An association between E(2) and
      the expression of 25 miRNAs was found 12 h after treatment. Among the most up
      regulated miRNAs were miR-196b and let-7h, and the most down-regulated miRNAs
      included miR-130c and miR-101a. Tissue-specific changes in the transcripts levels
      of estrogen receptors (Esr1, Esr2a, and Esr2b) and miRNAs were found after
      hormone treatment. The most up-regulated miR-196b and its precursors are highly
      expressed in the skin and showed similar tissue-specific expression patterns
      after treatment, indicating a common pattern of regulation by E(2). MiR-196b was
      shown to fine-tune the expression of its target gene Hoxb8a after treatment in
      whole-body homogenates. Taken together, our results suggest a novel pathway for
      the multifunctional and pleiotropic effects of estrogens and open new directions
      for future investigations of their association with miRNAs involved in estrogen
      regulated physiological processes and diseases.

PMID- 18096667
TI  - The regulation and function of the forkhead transcription factor, Forkhead box
      O1, is dependent on the progesterone receptor in endometrial carcinoma.
AB  - In many type I endometrial cancers, the PTEN gene is inactivated, which
      ultimately leads to constitutively active Akt and the inhibition of Forkhead box
      O1 (FOXO1), a member of the FOXO subfamily of Forkhead/winged helix family of
      transcription factors. The expression, regulation, and function of FOXO1 in
      endometrial cancer were investigated in this study. Immunohistochemical analysis
      of 49 endometrial tumor tissues revealed a decrease of FOXO1 expression in 95.9%
      of the cases compared with the expression in normal endometrium. In four
      different endometrial cancer cell lines (ECC1, Hec1B, Ishikawa, and RL95), FOXO1
      mRNA was expressed at similar levels; however, protein levels were low or
      undetectable in Ecc1, Ishikawa, and RL95 cells. Using small interfering RNA
      technology, we demonstrated that the low levels of FOXO1 protein were due to the
      involvement of Skp2, an oncogenic subunit of the Skp1/Cul1/F-box protein
      ubiquitin complex, given that silencing Skp2 increased FOXO1 protein expression
      in Ishikawa cells. Inhibition of Akt in Ishikawa cells also increased nuclear
      FOXO1 protein levels. Additionally, progestins increased FOXO1 protein levels,
      specifically through progesterone receptor B (PRB) as determined by using stably
      transfected PRA-specific and PRB-specific Ishikawa cell lines. Finally,
      overexpression of triple mutant (Tm) FOXO1 in the PR-specific Ishikawa cell lines
      caused cell cycle arrest and significantly decreased proliferation in the
      presence and absence of the progestin, R5020. Furthermore, TmFOXO1 overexpression
      induced apoptosis in PRB-specific cells in the presence and absence of ligand.
      Taken together, these data provide insight into the phosphoinositide-3
      kinase/Akt/FOXO pathway for the determination of progestin responsiveness and the
      development of alternate therapies for endometrial cancer.

PMID- 18096666
TI  - Tissue selectivity of the anabolic steroid, 19-nor-4-androstenediol-3beta,17beta
      diol in male Sprague Dawley rats: selective stimulation of muscle mass and bone
      mineral density relative to prostate mass.
AB  - Stimulation of prostate growth is a major concern with testosterone therapy in
      older hypogonadal men. As a result, nonsteroidal selective androgen receptor
      modulators with anabolic activity but less prostate stimulation are being
      developed. Anabolic steroids might exhibit similar tissue selectivity. We
      hypothesized the anabolic steroid 19-nor-4-androstenediol-3beta,17beta-diol
      (3beta,19-NA) would increase muscle, lean body mass (LBM), and bone mineral
      density (BMD) with little stimulation of prostate growth. Male Sprague Dawley
      rats were implanted with SILASTIC brand (Dow Corning, Midland, MI) capsules
      containing 3beta,19-NA (4, 8, or 16 cm), dihydrotestosterone (DHT) (8 cm), 19
      nortestosterone (16 cm), or four empty capsules after undergoing either a sham
      operation (intact) or orchidectomy (ORX). Serum gonadotropins, measured after 4,
      8, or 24 wk of treatment, were significantly lower in 3beta,19-NA-treated vs.
      untreated, intact, and ORX rats (P < 0.05), and testosterone was lowered by
      3beta,19-NA-treatment of intact animals. LBM and BMD were assessed after 20 wk,
      and 4 wk later, rats were killed for levator ani muscle and prostate weights.
      Compared with ORX rats, 3beta,19-NA-treated rats had dose-dependent higher
      levator ani muscle weights, LBM, and BMD, which were similar to intact and DHT
      treated rats at the highest 3beta,19-NA dose. In contrast, prostate weights in
      all 3beta,19-NA-treated groups were similar to ORX rats and lower than intact and
      DHT- and 19-nortestosterone-treated rats even at the highest 3beta,19-NA dose. In
      summary, 3beta,19-NA increases muscle and bone mass without significant
      stimulation of prostate growth, suggesting it may have some properties of a
      steroidal selective androgen receptor modulator. Anabolic steroids such as
      3beta,19-NA should be studied further to determine their mechanisms of tissue
      selectivity and effects in men.

PMID- 18096668
TI  - Hindbrain administration of estradiol inhibits feeding and activates estrogen
      receptor-alpha-expressing cells in the nucleus tractus solitarius of
      ovariectomized rats.
AB  - 17beta-estradiol (E2), acting via estrogen receptor (ER)-alpha, inhibits feeding
      in animals. One mechanism apparently involves an increase in the satiating
      potency of cholecystokinin (CCK) released from the small intestine by ingested
      food. For example, the satiating potency of intraduodenal lipid infusions is
      increased by E2 in ovariectomized rats; this increased satiation is dependent on
      CCK, and it is accompanied by increases in the numbers of ERalpha-positive cells
      that express c-Fos in a subregion of the caudal nucleus tractus solitarius (cNTS)
      that receives abdominal vagal afferent projections. To test whether direct
      administration of E2 to this area of the hindbrain is sufficient to inhibit food
      intake, we first implanted 0.2 microg estradiol benzoate (EB) in cholesterol or
      cholesterol alone either sc or onto the surface of the hindbrain over the cNTS.
      Food intake was significantly reduced after hindbrain EB implants but not after
      sc EB implants. Next we verified that equimolar hindbrain implants of E2 and EB
      had similar feeding-inhibitory effects and determined that only small amounts of
      E2 reached brain areas outside the dorsal caudal hindbrain after hindbrain
      implants of (3)H-labeled E2. Neither plasma estradiol concentration nor plasma
      inflammatory cytokine concentration was increased by either hindbrain or sc EB
      implants. Finally, hindbrain EB implants, but not sc implants, increased c-Fos in
      ERalpha-positive cells in the cNTS after ip injection of 4 microg/kg CCK-8. We
      conclude that E2, acting via ERalpha in cNTS neurons, including neurons
      stimulated by ip CCK, is sufficient to inhibit feeding.

PMID- 18096669
TI  - The cell-specific pattern of cholecystokinin peptides in endocrine cells versus
      neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6.
AB  - Most peptide hormone genes are, in addition to endocrine cells, also expressed in
      neurons. The peptide hormone cholecystokinin (CCK) is expressed in different
      molecular forms in cerebral neurons and intestinal endocrine cells. To understand
      this difference, we examined the roles of the neuroendocrine prohormone
      convertases (PC) 1/3, PC2, and PC5/6 by measurement of proCCK, processing
      intermediates and bioactive, alpha-amidated, and O-sulfated CCK peptides in
      cerebral and jejunal extracts of null mice, controls, and in the PC5/6-expressing
      SK-N-MC cell-line. In PC1/3 null mice, the synthesis of bioactive CCK peptide in
      the gut was reduced to 3% of the translational product, all of which was in the
      form of alpha-amidated and tyrosine O-sulfated CCK-22, whereas the neuronal
      synthesis in the brain was largely unaffected. This is opposite to the PC2 null
      mice in which only the cerebral synthesis was affected. SK-N-MC cells, which
      express neither PC1/3 nor PC2, synthesized alone the processing intermediate,
      glycine-extended CCK-22. Immunocytochemistry confirmed that intestinal endocrine
      CCK cells in wild-type mice express PC1/3 but not PC2. In contrast, cerebral CCK
      neurons contain PC2 and only little, if any, PC1/3. Taken together, the data
      indicate that PC1/3 governs the endocrine and PC2 the neuronal processing of
      proCCK, whereas PC5/6 contributes only to a modest endocrine synthesis of CCK-22.
      The results suggest that the different peptide patterns in the brain and the gut
      are due to different expression of PCs.

PMID- 18096671
TI  - Evidence of a role for androgens in embryonic stem cell function and
      differentiation.

PMID- 18096674
TI  - Drug lipophilicity and microsomal protein concentration as determinants in the
      prediction of the fraction unbound in microsomal incubations.
AB  - Two predictive tools have been proposed by Austin et al. (Drug Metab Dispos
      30:1497-1503, 2002) and Hallifax and Houston (Drug Metab Dispos 34:724-726, 2006)
      to estimate the fraction unbound in the incubation (fu(inc)). The current study
      was undertaken to elucidate the relative utility of these prediction tools over a
      range of drug lipophilicity and microsomal protein concentration. The fu(inc)
      data set (n = 127) comprised 35 drugs determined experimentally in this study and
      92 collated from Austin and Hallifax data. The observed fu(inc) values at three
      microsomal concentrations were compared with the estimates obtained using the
      Austin and Hallifax equations. In addition, the impact of variability in the logP
      on the fu(inc) predictions was assessed. The current analysis highlights the
      importance of accurate estimation of lipophilicity for the prediction of the
      fu(inc), regardless of the prediction equation used. Both equations represent
      useful tools for estimation of fu(inc) for low lipophilicity drugs (logP/D = 0
      3), especially at low microsomal protein concentration. However, the accuracy of
      fu(inc) predictions of highly lipophilic drugs was poor for both equations,
      implying that fu(inc) should be experimentally confirmed for drugs with logP/D
      >or= 3, unless the microsomal protein concentration is as low as 0.1 mg/ml, in
      which case a cutoff of logP/D >or= 5 can be applied. A significant difference in
      the predictions by the two proposed tools was observed in the area of
      intermediate lipophilicity (logP/D = 2.5-5), where the Hallifax equation provided
      more accurate fu(inc) predictions on average, irrespective of the microsomal
      protein concentration investigated.

PMID- 18096673
TI  - A human immunodeficiency virus protease inhibitor is a novel functional inhibitor
      of human pregnane X receptor.
AB  - Drug-drug interactions involving induction of cytochrome P450 enzymes (P450s) can
      lead to loss of drug efficacy. Certain drugs, particularly those used to treat
      mycobacterial and human immunodeficiency virus (HIV) infections, are especially
      prone to induce P450s. During studies to examine drug-interaction potential of
      compounds in cultured human hepatocytes, exposure with (S)-1-[(1S,3S,4S)-4-[(S)-2
      (3-benzyl-2-oxo-imidazolidin-1-yl)-3,3-dimethyl-butyrylamino]-3-hydroxy-5-phenyl
      1-(4-pyridin-2-yl-benzyl)-pentylcarbamoyl]-2,2-dimethyl-propyl-carbamic acid
      methyl ester (A-792611), a novel HIV protease inhibitor (PI) previously under
      investigation for the treatment of HIV infection, resulted in significant down
      regulation of constitutive CYP3A4 expression. Furthermore, coadministration of A
      792611 was found to attenuate CYP3A4 induction mediated by known inducers
      rifampin and efavirenz. A-792611 also attenuated the rifampin and ritonavir
      mediated activation of the human pregnane X receptor (PXR) in luciferase reporter
      assays. Microarray analysis on cultured human hepatocytes revealed that A-792611
      treatment down-regulated the expression of PXR target genes CYP3A4, CYP2B6,
      CYP2C8, and CYP2C9, whereas there was a lack of inductive effect observed in
      treated rat hepatocytes. A-792611 did not interact with other ligand-activated
      nuclear receptors that regulate P450 expression such as constitutive androstane
      receptor, farnesoid X receptor, vitamin D receptor, and peroxisome proliferator
      activated receptor alpha. These data suggest that A-792611 is a functional and
      effective human PXR inhibitor. Among the class of HIV-PIs, which are typically
      PXR activators, A-792611 seems to have a unique property for PXR antagonism and
      could be a useful tool for studying nuclear receptor pathway regulation.

PMID- 18096675
TI  - Hepatic synthesis and urinary elimination of acetaminophen glucuronide are
      exacerbated in bile duct-ligated rats.
AB  - Renal and intestinal disposition of acetaminophen glucuronide (APAP-GLU), a
      common substrate for multidrug resistance-associated proteins 2 and 3 (Mrp2 and
      Mrp3), was assessed in bile duct-ligated rats (BDL) 7 days after surgery using an
      in vivo perfused jejunum model with simultaneous urine collection. Doses of 150
      mg/kg b.w. (i.v.) or 1 g/kg b.w. (i.p.) of acetaminophen (APAP) were
      administered, and its glucuronide was determined in bile (only Shams), urine, and
      intestinal perfusate throughout a 150-min period. Intestinal excretion of APAP
      GLU was unchanged or decreased (-58%) by BDL for the 150 mg and 1 g/kg b.w. doses
      of APAP, respectively. In contrast, renal excretion was increased by 200 and
      320%, respectively. Western studies revealed decreased levels of apical Mrp2 in
      liver and jejunum but increased levels in renal cortex from BDL animals, whereas
      Mrp3 was substantially increased in liver and not affected in kidney or
      intestine. The global synthesis of APAP-GLU, determined as the sum of cumulative
      excretions, was higher in BDL rats (+51 and +110%) for these same doses of APAP
      as a consequence of a significant increase in functional liver mass, with no
      changes in specific glucuronidating activity. Expression of apical breast cancer
      resistance protein, which also transports nontoxic metabolites of APAP, was
      decreased by BDL in liver and renal cortex, suggesting a minor participation of
      this route. We demonstrate a more efficient hepatic synthesis and basolateral
      excretion of APAP-GLU followed by its urinary elimination in BDL group, the
      latter two processes consistent with up-regulation of liver Mrp3 and renal Mrp2.

PMID- 18096677
TI  - Improved naming after transcranial direct current stimulation in aphasia.
AB  - Transcranial direct current stimulation (tDCS) has been proposed as an adjuvant
      technique to improve functional recovery after ischaemic stroke. This study
      evaluated the effect of tDCS over the left frontotemporal areas in eight chronic
      non-fluent post-stroke aphasic patients. The protocol consisted of the assessment
      of picture naming (accuracy and response time) before and immediately after
      anodal or cathodal tDCS (2 mA, 10 minutes) and sham stimulation. Whereas anodal
      tDCS and sham tDCS failed to induce any changes, cathodal tDCS significantly
      improved the accuracy of the picture naming task by a mean of 33.6% (SEM 13.8%).

PMID- 18096676
TI  - CYP3A4-Mediated carbamazepine (CBZ) metabolism: formation of a covalent CBZ
      CYP3A4 adduct and alteration of the enzyme kinetic profile.
AB  - Carbamazepine (CBZ) is a widely prescribed anticonvulsant whose use is often
      associated with idiosyncratic hypersensitivity. Sera of CBZ-hypersensitive
      patients often contain anti-CYP3A antibodies, including those to a CYP3A23 K
      helix peptide that is also modified during peroxidative CYP3A4 heme
      fragmentation. We explored the possibility that cytochromes P450 (P450s) such as
      CYP3A4 bioactivate CBZ to reactive metabolite(s) that irreversibly modify the
      P450 protein. Such CBZ-P450 adducts, if stable in vivo, could engender
      corresponding serum P450 autoantibodies. Incubation with CBZ not only failed to
      inactivate functionally reconstituted, purified recombinant CYP3A4 or CYP3A4
      Supersomes in a time-dependent manner, but the inclusion of CBZ (0-1 mM) also
      afforded a concentration-dependent protection to CYP3A4 from inactivation by
      NADPH-induced oxidative uncoupling. Incubation of CYP3A4 Supersomes with (3)H-CBZ
      resulted in its irreversible binding to CYP3A4 protein with a stoichiometry of
      1.58 +/- 0.15 pmol (3)H-CBZ bound/pmol CYP3A4. Inclusion of glutathione (1.5 mM)
      in the incubation reduced this level to 1.09. Similar binding (1.0 +/- 0.4 pmol
      (3)H-CBZ bound/pmol CYP3A4) was observed after (3)H-CBZ incubation with
      functionally reconstituted, purified recombinant CYP3A4(His)(6). The CBZ-modified
      CYP3A4 retained its functional activity albeit at a reduced level, but its
      testosterone 6beta-hydroxylase kinetics were altered from sigmoidal (a
      characteristic profile of substrate cooperativity) to near-hyperbolic (Michaelis
      Menten) type, suggesting that CBZ may have modified CYP3A4 within its active
      site.

PMID- 18096678
TI  - Can electromyography objectively detect voluntary movement in disorders of
      consciousness?
AB  - Determining conscious processing in unresponsive patients relies on subjective
      behavioural assessment. Using data from hand electromyography, the authors
      studied the occurrence of subthreshold muscle activity in response to verbal
      command, as an objective indicator of awareness in 10 disorders of consciousness
      patients. One out of eight vegetative state patients and both minimally conscious
      patients (n = 2) demonstrated an increased electromyography signal specifically
      linked to command. These findings suggest electromyography could be used to
      assess awareness objectively in pathologies of consciousness.

PMID- 18096679
TI  - Hippocampal involvement in secondarily generalised seizures of extrahippocampal
      origin.
AB  - BACKGROUND AND AIMS: Recent data have revealed that clinically generalised tonic
      clonic seizures do not involve all brain regions electrophysiologically. The
      hippocampus in particular could be protected from epileptic activity by putative
      filtering properties of the dentate gyrus. Here we investigated if simple or
      complex focal seizures (SFS/CFS) and in particular secondarily generalised tonic
      clonic seizures (SGS) of extrahippocampal onset (EHO) spare the hippocampus and
      if there are promotive factors. METHODS: We retrospectively assessed clinical,
      electrophysiological, imaging and histopathological data from patients undergoing
      presurgical evaluation of focal epilepsy with hippocampal depth and
      extrahippocampal subdural electrodes and selected those suffering from SGS of
      EHO. We further subdivided this patient sample according to qualitative MRI
      criteria into a HL(-) group, with an extrahippocampal lesion only, and a HL(+)
      group, displaying an extrahippocampal and additional hippocampal lesion. RESULTS:
      14 patients (seven in each group) fulfilling the inclusion criteria had a total
      of 43 SGS, of which 35 were of EHO. Whereas only 68% of SFS/CFS of EHO propagated
      into the hippocampus, all SGS of EHO invaded the hippocampi independently of the
      ictal propagation pattern or degree of hippocampal pathology. All hippocampi in
      the HL(-) group displayed interictal epileptiform activity and even seizure onset
      in two patients. CONCLUSIONS: In our patient sample, the human hippocampus was
      not spared during SGS of EHO, but was invariably invaded by epileptic activity.
      The presence of spontaneous epileptic activity in the HL(-) group revealed
      persistent modifications in hippocampal excitability that might be due to
      secondary epileptogenesis in the hippocampus following repeated seizures of EHO.

PMID- 18096680
TI  - Long-term occurrence of death and cardiovascular events in patients with
      transient ischaemic attack or minor ischaemic stroke: comparison between arterial
      and cardiac source of the index event.
AB  - BACKGROUND AND AIMS: Published data suggest that patients with cerebral ischaemia
      and atrial fibrillation (CIAF) have higher inhospital mortality than patients
      with cerebral ischaemia of arterial origin (CIAO). Data on long term risks are
      scarce. We compared the long term risks of death and vascular events (VE) between
      these groups. METHODS: We extended the follow-up of 2473 patients from the Dutch
      TIA Trial (recruitment March 1986 to March 1989, all treated with aspirin; CIAO)
      and 186 Dutch participants of the European Atrial Fibrillation Trial (recruitment
      June 1988 to May 1992, 26% on anticoagulants during the trial; CIAF). Hazard
      ratios (HRs) for death and VE of CIAF versus CIAO were analysed by means of Cox
      regression analysis and adjusted for age, sex and several cardiovascular risk
      factors. RESULTS: After a mean follow-up of 10.1 years, 1484 patients with CIAO
      had died and 1336 had suffered at least one VE (377 cardiac, 455 stroke). Mean
      follow-up of the CIAF patients was 6.8 years; 150 patients had died and 136 had
      suffered at least one VE (41 cardiac, 63 stroke). Adjusted HRs (CIAF vs CIAO)
      were 1.46 (95% CI 1.22 to 1.74) for death, 1.49 (1.24 to 1.79) for first VE, 1.94
      (1.47 to 2.55) for first stroke and 1.41 (1.01 to 1.96) for first cardiac event.
      These HRs were essentially the same as those for the duration of the trials.
      CONCLUSION: Our study shows that the long term risk of death or vascular events
      is 1.5 times higher in patients with CIAF than in those with CIAO, after
      adjustment for differences between the groups.

PMID- 18096681
TI  - Combined EEG-fMRI and tractography to visualise propagation of epileptic
      activity.
AB  - In a patient with refractory temporal lobe epilepsy, EEG-fMRI showed activation
      in association with left anterior temporal interictal discharges, in the left
      temporal, parietal and occipital lobes. Dynamic causal modelling suggested
      propagation of neural activity from the temporal focus to the area of occipital
      activation. Tractography showed connections from the site of temporal lobe
      activation to the site of occipital activation. This demonstrates the principle
      of combining EEG-fMRI and tractography to delineate the pathways of propagation
      of epileptic activity.

PMID- 18096682
TI  - Detection of Huntington's disease decades before diagnosis: the Predict-HD study.
AB  - OBJECTIVE: The objective of the Predict-HD study is to use genetic,
      neurobiological and refined clinical markers to understand the early progression
      of Huntington's disease (HD), prior to the point of traditional diagnosis, in
      persons with a known gene mutation. Here we estimate the approximate onset and
      initial course of various measurable aspects of HD relative to the time of
      eventual diagnosis. METHODS: We studied 438 participants who were positive for
      the HD gene mutation, but did not yet meet the diagnostic criteria for HD and had
      no functional decline. Predictability of baseline cognitive, motor, psychiatric
      and imaging measures was modelled non-linearly using estimated time until
      diagnosis (based on CAG repeat length and current age) as the predictor. RESULTS:
      Estimated time to diagnosis was related to most clinical and neuroimaging
      markers. The patterns of association suggested the commencement of detectable
      changes one to two decades prior to the predicted time of clinical diagnosis. The
      patterns were highly robust and consistent, despite the varied types of markers
      and diverse measurement methodologies. CONCLUSIONS: These findings from the
      Predict-HD study suggest the approximate time scale of measurable disease
      development, and suggest candidate disease markers for use in preventive HD
      trials.

PMID- 18096685
TI  - Cilia--the masterplan.

PMID- 18096686
TI  - The diversity of cytoplasmic microtubules.

PMID- 18096687
TI  - Nonmuscle myosin II moves in new directions.
AB  - For many years, analyses of the role of the actomyosin cytoskeleton in many basic
      cellular processes have centered on actin. Increasingly, however, a number of
      investigators are examining proteins that are proximal to actin; in particular,
      nonmuscle myosin II (NMII). Recent experiments have increased our understanding
      of the role of NMII in three related cellular activities: generation of cell
      polarity, cell migration and cell-cell adhesion. Progress has been particularly
      promising thanks to the use of new microscopic, genetic and biochemical
      techniques. In mammalian systems, generation of transgenic mice and the
      introduction of specific siRNAs have been useful in deciphering the role of the
      three different isoforms of NMII: NMIIA, NMIIB and NMIIC. Studies in Drosophila
      and Aplysia, which are informative model systems for investigating the function
      of NMII, have also shed light on NMII. Recent work examines the contractile and
      structural roles that NMII plays at cell-cell boundaries, and both its
      contractile and actin-crosslinking roles in cell migration. In addition, NMII
      might also function as a scaffold molecule, anchoring signaling molecules, such
      as kinases and Rho GTPase guanine nucleotide exchange factors.

PMID- 18096688
TI  - Formation and function of Weibel-Palade bodies.
AB  - Weibel-Palade bodies (WPBs) are secretory organelles used for post-synthesis
      storage in endothelial cells that can, very rapidly, be triggered to release
      their contents. They carry a variety of bioactive molecules that are needed to
      mount a rapid response to the complex environment of cells that line blood
      vessels. They store factors that are essential to haemostasis and inflammation,
      as well as factors that modulate vascular tonicity and angiogenesis. The number
      of WPBs and their precise content vary between endothelial tissues, reflecting
      their differing physiological circumstances. The particular functional demands of
      the highly multimerised haemostatic protein von Willebrand Factor (VWF), which is
      stored in WPBs as tubules until release, are responsible for the cigar shape of
      these granules. How VWF tubules drive the formation of these uniquely shaped
      organelles, and how WPB density increases during maturation, has recently been
      revealed by EM analysis using high-pressure freezing and freeze substitution. In
      addition, an AP1/clathrin coat has been found to be essential to WPB formation.
      Following recruitment of cargo at the TGN, there is a second wave of recruitment
      that delivers integral and peripheral membrane proteins to WPBs, some of which is
      AP3 dependent.

PMID- 18096689
TI  - Phosphorylation of vascular endothelial cadherin controls lymphocyte emigration.
AB  - Lymphocytes emigrate from the circulation to target tissues through the
      microvascular endothelial cell (EC) barrier. During paracellular transmigration
      cell-cell junctions have been proposed to disengage and provide homophilic and
      heterophilic interaction surfaces in a zip-like process. However, it is not known
      whether ECs modulate junction proteins during this process. Here we show that
      tyrosine phosphorylation of adherens junction vascular endothelial cadherin (VEC)
      is required for successful transendothelial lymphocyte migration. We found that
      adhesion of lymphocytes or activation of the endothelial intercellular adhesion
      molecule 1 (ICAM1) led to tyrosine phosphorylation of VEC. Substitution of
      tyrosine for phenylalanine in VEC at positions 645, 731 or 733 produced ECs that
      were significantly less permissive to lymphocyte migration. We also found that
      these same tyrosine residues are involved in ICAM1-dependent changes of VEC
      phosphorylation. ICAM1 activation enhanced transendothelial permeability,
      suggesting the occurrence of junction disassembly. In agreement, the expression
      of VEC mutated at Y645F, Y731F or Y733F predominantly affected lymphocyte
      transmigration in paracellular areas. Taken together, these results demonstrate
      that phosphorylation of adherens junctions constitutes a molecular endpoint of
      lymphocyte-induced vascular EC signaling and may be exploited as a new target of
      anti-inflammatory therapies.

PMID- 18096690
TI  - Activation of growth hormone receptors by growth hormone and growth hormone
      antagonist dimers: insights into receptor triggering.
AB  - GH binds dimerized GH receptors (GHRs) to form a trimolecular complex and induces
      downstream signaling events. The mechanism by which GH binding converts the
      inactive predimerized GHR to its active signaling conformation is uncertain. GH
      has no axis of symmetry. Its interaction with GHR is mediated by two asymmetric
      binding sites on GH, each with distinct affinity. Site 1 is of high affinity and
      is thought to mediate the first binding step. Mutation of binding site 2 (as in
      the human GH mutant, G120R) disrupts the second binding but leaves site 1 binding
      intact. G120R is a GH antagonist; it binds only one GHR and thus fails to signal,
      and it prevents productive GHR binding by normal GH. We previously demonstrated
      that prolactin receptor signaling was achieved by a dimeric version of a
      prolactin antagonist. We now employ assays of cellular signaling and receptor
      conformational changes to examine whether GH molecules harboring two site 1
      regions can trigger GHR activation. We used recombinantly produced GH-GH and
      G120R-G120R dimers in which monomers in tandem are connected by a short linker
      peptide. Rabbit GHR-expressing human fibrosarcoma cells (C14) were treated with
      GH, G120R, GH-GH, or G120R-G120R. As expected, GH and GH-GH, but not G120R,
      induced GHR disulfide linkage, as assessed by anti-GHR blotting of cell extracts
      resolved by SDS-PAGE under nonreducing conditions. Disulfide linkage of GHRs
      reflects attainment of the active signaling conformation. Likewise, GH and GH-GH,
      but not G120R, caused Janus kinase 2 (JAK2) and signal transducer and activator
      of transcription 5 (STAT5) activation. Notably, G120R-G120R, despite its lack of
      an intact site 2 in either dimer partner, also promoted GHR disulfide linkage and
      JAK2 and STAT5 activation, albeit less potently than either GH or GH-GH. Time
      course responses of the three agonists were similar in terms of JAK2 and STAT5
      activation. Pretreatment of cells with our conformation-sensitive inhibitory
      monoclonal antibody, anti-GHR ext-mAb, prevented ligand-induced receptor
      activation for all three agonists. GHR was also rendered less immunoprecipitable
      by anti-GHR ext-mAb after treatment with these agonists. These results are
      important in that they indicate that a ligand with two intact binding sites 1
      causes GHR to adopt similar conformational changes as does GH and thus triggers
      activation of JAK2 and downstream signaling. Furthermore, we infer that there is
      substantial flexibility in the GHR extracellular domain, such that it
      productively accommodates GH dimers that are much larger than GH.

PMID- 18096691
TI  - Specific physiological roles for signal transducer and activator of transcription
      3 in leptin receptor-expressing neurons.
AB  - Leptin is a fat-derived hormone that exerts pleiotropic effects on energy balance
      and neuroendocrine functions. Mice defective in leptin or its receptor [leptin
      receptor, isoform b (LepRb)] exhibit profound obesity, infertility, and reduced
      linear growth. Leptin binding to its receptor triggers multiple signaling
      pathways, including signal transducer and activator of transcription 3 (Stat 3),
      phosphatidylinositol-3-kinase, and ERK. A considerable amount of effort has been
      focused on how these signaling pathways mediate diverse leptin functions. Mice
      containing a mutant LepRb incapable of Stat3 signaling are obese but remain
      fertile with enhanced linear growth. In contrast, deletion of Stat3 in the whole
      brain with Nestin-Cre results in infertility and decreased linear growth, in
      addition to obesity. The additional phenotypes of the Nestin-mediated deletion
      could reflect Stat3 action in non-LepRb neurons or leptin-independent Stat3
      actions in LepRb neurons. To resolve this discrepancy and to gain more insight
      into the metabolic actions of Stat3, we have generated mice in which Stat3 is
      disrupted specifically in LepRb neurons after the onset of leptin receptor
      expression. We show that mutant mice exhibit profound obesity with increased
      linear growth and normal fertility. In addition, impaired glycemic control in
      these animals correlates with their degree of obesity. These results demonstrate
      that Stat3 in LepRb neurons does not regulate linear growth or fertility. These
      results further suggest that leptin's effects on growth and reproduction are
      mediated by other signaling pathways, and that Stat3-mediated control of these
      functions is mediated independently of leptin and LepRb neurons.

PMID- 18096692
TI  - Control of estradiol-directed gene transactivation by an intracellular estrogen
      binding protein and an estrogen response element-binding protein.
AB  - New World primates exhibit a form of resistance to estrogens that is associated
      with overexpression of an estrogen response element (ERE)-binding protein (ERE
      BP) and an intracellular estradiol (E(2))-binding protein (IEBP). Both proteins
      suppress E(2)-mediated transcription when overexpressed in estrogen receptor
      alpha (ERalpha)-positive cells. Although ERE-BP acts as a competitor for ERE
      occupancy by liganded ERalpha, the function of IEBP and its human homolog, heat
      shock protein 27 (hsp27), is less clear. In data presented here, we have used
      E(2)-responsive human MCF-7 breast cancer cells to show that IEBP/hsp27 can
      regulate estrogen signaling as a cytosolic decoy for E(2) and as a protein
      chaperone for ERalpha. Furthermore, co-immunoprecipitation, colocalization, yeast
      two-hybrid, and glutathione S-transferase pull-down analyses indicate that
      IEBP/hsp27 also interacts with ERE-BP to form a dynamic complex that appears to
      cycle between the cytoplasm and nucleus during normal estrogen signaling.
      Overexpression of either IEBP/hsp27 or ERE-BP in MCF-7 cells resulted in abnormal
      subcellular distribution of the IEBP/hsp27 and ERE-BP, with concomitant
      dysregulation of ERE occupancy as determined by chromatin immunoprecipitation. We
      hypothesize that IEBP/hsp27 and ERE-BP not only cause hormone resistance in New
      World primates but are also crucial to normal estrogen signaling in human cells.
      This appears to involve a physical association between the two proteins to form a
      complex that is able to interact with both E(2) and ERalpha in cytosolic and
      nuclear compartments.

PMID- 18096693
TI  - Glucocorticoid prevents brain-derived neurotrophic factor-mediated maturation of
      synaptic function in developing hippocampal neurons through reduction in the
      activity of mitogen-activated protein kinase.
AB  - An increased level of glucocorticoid may be related to the pathophysiology of
      depressive disorder. The involvement of brain-derived neurotrophic factor (BDNF)
      in the antidepressive effect has also been suggested; however, the possible
      influence of glucocorticoid on the action of BDNF in the developing central
      nervous system has not been elucidated. In this study, we investigated the effect
      of glucocorticoid (dexamethasone, DEX) on synaptic maturation and function
      enhanced by BDNF in early developing hippocampal neurons. In the immature stage,
      BDNF increased the outgrowth of dendrites and the expression of synaptic proteins
      including glutamate receptors and presynaptic proteins. Pretreatment with DEX
      significantly inhibited the BDNF-dependent up-regulation of both dendritic
      outgrowth and synaptic proteins. In the more mature stage, the BDNF-reinforced
      postsynaptic Ca(2+) influx was decreased by DEX. BDNF-enhanced presynaptic
      glutamate release was also suppressed. RU486, a glucocorticoid receptor
      antagonist, canceled the DEX-dependent blocking effect on the action of BDNF.
      After down-regulation of glucocorticoid receptor by small interfering RNA
      application, no inhibitory effect of DEX on the BDNF-increased synaptic proteins
      was observed. Interestingly, the BDNF-activated MAPK/ERK pathway, which is an
      essential intracellular signaling pathway for the BDNF-increased synaptic
      proteins, was reduced by DEX. These results suggest that BDNF-mediated synaptic
      maturation is disturbed after neurons are exposed to high-level glucocorticoid in
      their development stage.

PMID- 18096694
TI  - The phytoestrogen coumestrol is a naturally occurring antagonist of the human
      pregnane X receptor.
AB  - Antagonizing the action of the human nuclear xenobiotic receptor pregnane X
      receptor (PXR) may have important clinical implications in preventing drug-drug
      interactions and improving therapeutic efficacy. We provide evidence that a
      naturally occurring phytoestrogen, coumestrol, is an antagonist of the nuclear
      receptor PXR (NR1I2). In transient transfection assays, coumestrol was able to
      suppress the agonist effects of SR12813 on human PXR activity. PXR activity was
      assessed and correlated with effects on the metabolism of the anesthetic
      tribromoethanol and on gene expression in primary human hepatocytes. We found
      that coumestrol was able to suppress the effects of PXR agonists on the
      expression of the known PXR target genes, CYP3A4 and CYP2B6, in primary human
      hepatocytes as well as inhibit metabolism of tribromoethanol in humanized PXR
      mice. Coumestrol at concentrations above 1.0 microm competed in scintillation
      proximity assays with a labeled PXR agonist for binding to the ligand-binding
      cavity. However, mammalian two-hybrid assays and transient transcription data
      using ligand-binding-cavity mutant forms of PXR show that coumestrol also
      antagonizes coregulator recruitment. This effect is likely by binding to a
      surface outside the ligand-binding pocket. Taken together, these data imply that
      there are antagonist binding site(s) for coumestrol on the surface of PXR. These
      studies provide the basis for development of novel small molecule inhibitors of
      PXR with the ultimate goal of clinical applications toward preventing drug-drug
      interactions.

PMID- 18096695
TI  - The antiapoptotic role of pregnane X receptor in human colon cancer cells.
AB  - The orphan nuclear receptor pregnane X receptor (PXR) plays an important role in
      the detoxification of foreign and endogenous chemicals, including bile acids. PXR
      promotes bile acid elimination by activating bile acid-detoxifying enzymes and
      transporters. Certain bile acids are known to promote colonic carcinogenesis by
      inducing colon cancer cell apoptosis. However, whether and how PXR plays a role
      in colon cancer apoptosis has not been reported. In this study, we showed that
      activation of PXR by genetic (using a constitutively activated PXR) or
      pharmacological (using PXR agonist rifampicin) means protected the PXR
      overexpressing colon cancer HCT116 cells from deoxycholic acid-induced apoptosis.
      Interestingly, activation of PXR also protected HCT116 cells from adriamycin
      induced cell death, suggesting that the antiapoptotic effect of PXR was not bile
      acid specific. Moreover, the antiapoptotic effect of PXR in HCT116 cells appeared
      to be independent of xenobiotic enzyme regulation, because these cells had little
      basal and inducible expression of bile acid-detoxifying enzymes. Instead,
      SuperArray analysis showed that PXR-mediated deoxycholic acid resistance was
      associated with up-regulation of multiple antiapoptotic genes, including BAG3,
      BIRC2, and MCL-1, and down-regulation of proapoptotic genes, such as BAK1 and
      TP53/p53. Treatment with rifampicin in colon cancer LS180 cells, a cell line
      known to express endogenous PXR, also inhibited apoptosis. Activation of PXR in
      transgenic mice inhibited bile acid-induced colonic epithelial apoptosis and
      sensitized mice to dimethylhydrazine-induced colonic carcinogenesis, suggesting
      that the antiapoptotic effect of PXR is conserved in normal colon epithelium. In
      summary, our results have established the antiapoptotic role of PXR in both human
      colon cancer cells and normal mouse colon epithelium.

PMID- 18096696
TI  - The third intracellular loop of the human somatostatin receptor 5 is crucial for
      arrestin binding and receptor internalization after somatostatin stimulation.
AB  - Somatostatin (SS) is a widely distributed polypeptide that exerts inhibitory
      effects on hormone secretion and cell proliferation by interacting with five
      different receptors (SST1-SST5). Beta-arrestins have been implicated in
      regulating SST internalization, but the structural domains mediating this effect
      are largely unknown. The aim of this study was to characterize the intracellular
      mechanisms responsible for internalization of human SST5 in the rat pituitary
      cell line GH3 and to identify the SST5 structural domains involved in this
      process. To this purpose we evaluated, by fluorescence microscopy and biochemical
      assay, the ability of wild-type, progressive C-terminal truncated and third
      cytoplasmatic loop mutants SST5-DsRed to associate with beta-arrestin-enhanced
      green fluorescent protein and to internalize under SS28 stimulation. The
      truncated mutants were comparable to the wild-type receptor with respect to
      recruitment of beta-arrestin-2 and internalization, whereas the third loop
      mutants R240W, S242A, and T247A showed the abolishment or reduction of arrestin
      association and a significant reduction of receptor internalization (14.4%, 29%,
      and 30.9% vs. 52.4% of wild type) and serine phosphorylation upon SS28
      stimulation. Moreover, we evaluated the ability of simultaneous mutation of these
      three residues (R240, S242, and T247) and C-terminal truncated receptors to
      internalize. The progressive truncation of the C-terminal tail resulted in a
      progressive increased internalization (21.6%, 36.7%, and 41%, respectively) with
      respect to the full-length total third-loop mutant (15%). In conclusion, our
      results indicate the SST5 third intracellular loop as an important mediator of
      beta-arrestin/receptor interaction and receptor internalization, whereas they
      suggest that residues 328-347 within the C terminus may play an inhibitory role
      in receptor internalization.

PMID- 18096697
TI  - A single luminally continuous sarcoplasmic reticulum with apparently separate
      Ca2+ stores in smooth muscle.
AB  - Whether or not the sarcoplasmic reticulum (SR) is a continuous, interconnected
      network surrounding a single lumen or comprises multiple, separate Ca2+ pools was
      investigated in voltage-clamped single smooth muscle cells using local photolysis
      of caged compounds and Ca2+ imaging. The entire SR could be depleted or refilled
      from one small site via either inositol 1,4,5-trisphosphate receptors (IP3R) or
      ryanodine receptors (RyR) suggesting the SR is luminally continuous and that Ca2+
      may diffuse freely throughout. Notwithstanding, regulation of the opening of RyR
      and IP3R, by the [Ca2+] within the SR, may create several apparent SR elements
      with various receptor arrangements. IP3R and RyR may appear to exist entirely on
      a single store, and there may seem to be additional SR elements that express
      either only RyR or only IP3R. The various SR receptor arrangements and apparently
      separate Ca2+ storage elements exist in a single luminally continuous SR entity.

PMID- 18096698
TI  - Novel dehydrogenase catalyzes oxidative hydrolysis of carbon-nitrogen double
      bonds for hydrazone degradation.
AB  - Hydrazines and their derivatives are versatile artificial and natural compounds
      that are metabolized by elusive biological systems. Here we identified
      microorganisms that assimilate hydrazones and isolated the yeast, Candida
      palmioleophila MK883. When cultured with adipic acid bis(ethylidene hydrazide) as
      the sole source of carbon, C. palmioleophila MK883 degraded hydrazones and
      accumulated adipic acid dihydrazide. Cytosolic NAD+- or NADP+-dependent hydrazone
      dehydrogenase (Hdh) activity was detectable under these conditions. The
      production of Hdh was inducible by adipic acid bis(ethylidene hydrazide) and the
      hydrazone, varelic acid ethylidene hydrazide, under the control of carbon
      catabolite repression. Purified Hdh oxidized and hydrated the C=N double bond of
      acetaldehyde hydrazones by reducing NAD+ or NADP+ to produce relevant hydrazides
      and acetate, the latter of which the yeast assimilated. The deduced amino acid
      sequence revealed that Hdh belongs to the aldehyde dehydrogenase (Aldh)
      superfamily. Kinetic and mutagenesis studies showed that Hdh formed a ternary
      complex with the substrates and that conserved Cys is essential for the activity.
      The mechanism of Hdh is similar to that of Aldh, except that it catalyzed
      oxidative hydrolysis of hydrazones that requires adding a water molecule to the
      reaction catalyzed by conventional Aldh. Surprisingly, both Hdh and Aldh from
      baker's yeast (Ald4p) catalyzed the Hdh reaction as well as aldehyde oxidation.
      Our findings are unique in that we discovered a biological mechanism for
      hydrazone utilization and a novel function of proteins in the Aldh family that
      act on C=N compounds.

PMID- 18096699
TI  - Caveolin regulates endocytosis of the muscle repair protein, dysferlin.
AB  - Dysferlin and Caveolin-3 are plasma membrane proteins associated with muscular
      dystrophy. Patients with mutations in the CAV3 gene show dysferlin
      mislocalization in muscle cells. By utilizing caveolin-null cells, expression of
      caveolin mutants, and different mutants of dysferlin, we have dissected the site
      of action of caveolin with respect to dysferlin trafficking pathways. We now show
      that Caveolin-1 or -3 can facilitate exit of a dysferlin mutant that accumulates
      in the Golgi complex of Cav1(-/-) cells. In contrast, wild type dysferlin reaches
      the plasma membrane but is rapidly endocytosed in Cav1(-/-) cells. We demonstrate
      that the primary effect of caveolin is to cause surface retention of dysferlin.
      Caveolin-1 or Caveolin-3, but not specific caveolin mutants, inhibit endocytosis
      of dysferlin through a clathrin-independent pathway colocalizing with
      internalized glycosylphosphatidylinositol-anchored proteins. Our results provide
      new insights into the role of this endocytic pathway in surface remodeling of
      specific surface components. In addition, they highlight a novel mechanism of
      action of caveolins relevant to the pathogenic mechanisms underlying caveolin
      associated disease.

PMID- 18096701
TI  - Mutants of Mucor hiemalis endo-beta-N-acetylglucosaminidase show enhanced
      transglycosylation and glycosynthase-like activities.
AB  - Endo-beta-N-acetylglucosaminidase from Mucor hiemalis (Endo-M), a family 85
      glycoside hydrolase, acts on the beta1,4 linkage of N,N'-diacetylchitobiose
      moiety in the N-linked glycans of glycoproteins and catalyzes not only the
      hydrolysis reaction but also the transglycosylation reaction that transfers the
      releasing sugar chain to an acceptor other than water to form a new glycosidic
      linkage. The transglycosylation activity of Endo-M holds a great promise for the
      chemo-enzymatic synthesis and glyco-engineering of glycoproteins, but the
      inherent hydrolytic activity for product hydrolysis and low transglycosylation
      have hampered its broad applications. This paper describes the site-directed
      mutagenesis on residues in the putative catalytic region of Endo-M to generate
      mutants with superior transglycosylation activity. Two interesting mutants were
      discovered. The Y217F mutant was found to possess much enhanced
      transglycosylation activity and yet much diminished hydrolytic activity in
      comparison with the wild-type Endo-M. Kinetic analyses revealed that the Km value
      of Y217F for an acceptor substrate 4-methylumbelliferyl-beta-D-N
      acetylglucosaminide was only one-tenth of that of the wild-type, implicating a
      much higher affinity of Y217F for the acceptor substrate than the wild-type. The
      other mutant, N175A, acts like a glycosynthase. It was found that mutation at
      Asn175"knocked out" the hydrolytic activity, but the mutant was able to take the
      highly active sugar oxazolines (the transition state mimics) as donor substrates
      for transglycosylation. This is the first glycosynthase derived from endo-beta-N
      acetylglucosaminidases that proceed via a substrate-assisted mechanism. Our
      findings provide further insights on the substrate-assisted mechanism of GH85.
      The usefulness of the novel glycosynthase was exemplified by the efficient
      synthesis of a human immunodeficiency virus, type 1 (HIV-1) glycopeptide with
      potent anti-HIV activity.

PMID- 18096700
TI  - Reticulon RTN2B regulates trafficking and function of neuronal glutamate
      transporter EAAC1.
AB  - Excitatory amino acid transporters (EAATs) are the primary regulators of
      extracellular glutamate concentrations in the central nervous system. Their
      dysfunction may contribute to several neurological diseases. To date, five
      distinct mammalian glutamate transporters have been cloned. In brain, EAAC1
      (excitatory amino acid carrier 1) is the primary neuronal glutamate transporter,
      localized on the perisynaptic membranes that are near release sites. Despite its
      potential importance in synaptic actions, little is known concerning the
      regulation of EAAC1 trafficking from the endoplasmic reticulum (ER) to the cell
      surface. Previously, we identified an EAAC1-associated protein, GTRAP3-18, an ER
      protein that prevents ER exit of EAAC1 when induced. Here we show that RTN2B, a
      member of the reticulon protein family that mainly localizes in the ER and ER
      exit sites interacts with EAAC1 and GTRAP3-18. EAAC1 and GTRAP3-18 bind to
      different regions of RTN2B. Each protein can separately and independently form
      complexes with EAAC1. RTN2B enhances ER exit and the cell surface composition of
      EAAC1 in heterologous cells. Expression of short interfering RNA-mediated
      knockdown of RTN2B decreases the EAAC1 protein level in neurons. Overall, our
      results suggest that RTN2B functions as a positive regulator in the delivery of
      EAAC1 from the ER to the cell surface. These studies indicate that transporter
      exit from the ER controlled by the interaction with its ER binding partner
      represents a critical regulatory step in glutamate transporter trafficking to the
      cell surface.

PMID- 18096702
TI  - Characterization of the essential activities of Saccharomyces cerevisiae Mtr4p, a
      3'->5' helicase partner of the nuclear exosome.
AB  - Mtr4p belongs to the Ski2p family of DEVH-box containing proteins and is required
      for processing and degradation of a variety of RNA substrates in the nucleus. In
      particular, Mtr4p is required for creating the 5.8 S ribosomal RNA from its 7 S
      precursor, proper 3'-end processing of the U4 small nuclear RNA and some small
      nucleolar RNAs, and degradation of aberrant mRNAs and tRNAs. In these studies we
      have shown that Mtr4p has RNA-dependent ATPase (or dATPase) activity that is
      stimulated effectively by likely substrates (e.g. tRNA) but surprisingly weakly
      by poly(A). Using an RNA strand-displacement assay, we have demonstrated that
      Mtr4p can, in the presence of ATP or dATP, unwind the duplex region of a partial
      duplex RNA substrate in the 3'-->5' direction. We have examined the ability of
      Mtr4p to bind model RNA substrates in the presence of nucleotides that mimic the
      stages (i.e. ATP-bound, ADP-bound, and nucleotide-free) of the unwinding
      reaction. Our results demonstrate that the presence of a non-hydrolyzable ATP
      analog allows Mtr4p to discriminate between partial duplex RNA substrates,
      binding a 3'-tailed substrate with 5-fold higher affinity than a 5'-tailed
      substrate. In addition, Mtr4p displays a marked preference for binding to poly(A)
      RNA relative to an oligoribonucleotide of the same length and a random sequence.
      This binding exhibits apparent cooperativity and different dynamic behavior from
      binding to the random single-stranded RNA. This unique binding mode might be
      employed primarily for degradation.

PMID- 18096703
TI  - Galphaz negatively regulates insulin secretion and glucose clearance.
AB  - Relatively little is known about the in vivo functions of the alpha subunit of
      the heterotrimeric G protein Gz (Galphaz). Clues to one potential function
      recently emerged with the finding that activation of Galphaz inhibits glucose
      stimulated insulin secretion in an insulinoma cell line (Kimple, M. E., Nixon, A.
      B., Kelly, P., Bailey, C. L., Young, K. H., Fields, T. A., and Casey, P. J.
      (2005) J. Biol. Chem. 280, 31708-31713). To extend this study in vivo, a Galphaz
      knock-out mouse model was utilized to determine whether Galphaz function plays a
      role in the inhibition of insulin secretion. No differences were discovered in
      the gross morphology of the pancreatic islets or in the islet DNA, protein, or
      insulin content between Galphaz-null and wild-type mice. There was also no
      difference between the insulin sensitivity of Galphaz-null mice and wild-type
      controls, as measured by insulin tolerance tests. Galphaz-null mice did, however,
      display increased plasma insulin concentrations and a corresponding increase in
      glucose clearance following intraperitoneal and oral glucose challenge as
      compared with wild-type controls. The increased plasma insulin observed in
      Galphaz-null mice is most likely a direct result of enhanced insulin secretion,
      since pancreatic islets isolated from Galphaz-null mice exhibited significantly
      higher glucose-stimulated insulin secretion than those of wild-type mice.
      Finally, the increased insulin secretion observed in Galphaz-null islets appears
      to be due to the relief of a tonic inhibition of adenylyl cyclase, as cAMP
      production was significantly increased in Galphaz-null islets in the absence of
      exogenous stimulation. These findings indicate that Galphaz may be a potential
      new target for therapeutics aimed at ameliorating beta-cell dysfunction in Type 2
      diabetes.

PMID- 18096704
TI  - Cell type-specific post-transcriptional regulation of production of the potent
      antiangiogenic and proatherogenic protein thrombospondin-1 by high glucose.
AB  - Hyperglycemia is an independent risk factor for development of vascular diabetic
      complications. Vascular dysfunction in diabetics manifests in a tissue-specific
      manner; macrovasculature is affected by atherosclerotic lesions, and
      microvascular complications are described as "aberrant angiogenesis": in the same
      patient angiogenesis is increased in some tissues (e.g. retinal
      neovascularization) and decreased in others (e.g. in skin). Molecular cell- and
      tissue-specific mechanisms regulating the response of vasculature to
      hyperglycemia remain unclear. Thrombospondin-1 (TSP-1), a potent antiangiogenic
      and proatherogenic protein, has been implicated in the development of several
      vascular diabetic complications (atherosclerosis, nephropathy, and
      cardiomyopathy). This study examines cell type-specific regulation of production
      of thrombospondin-1 by high glucose. We previously reported the increased
      expression of TSP-1 in the large arteries of diabetic animals. mRNA and protein
      levels were up-regulated in response to high glucose. Unlike in macrovascular
      cells, TSP-1 protein levels are dramatically decreased in response to high
      glucose in microvascular endothelial cells and retinal pigment epithelial cells
      (RPE). This down-regulation is post-transcriptional; mRNA levels are increased.
      In situ mRNA hybridization and immunohistochemistry revealed that the level of
      mRNA is up-regulated in RPE of diabetic rats, whereas the protein level is
      decreased. This cell type-specific posttranscriptional suppression of TSP-1
      production in response to high glucose in microvascular endothelial cells and RPE
      is controlled by untranslated regions of TSP-1 mRNA that regulate coupling of TSP
      1 mRNA to polysomes and its translation. The cell-specific regulation of TSP-1
      suggests a potential mechanism for the aberrant angiogenesis in diabetics and TSP
      1 involvement in development of various vascular diabetic complications.

PMID- 18096705
TI  - Wnt-7a modulates the synaptic vesicle cycle and synaptic transmission in
      hippocampal neurons.
AB  - Wnt signaling is essential for neuronal development and the maintenance of the
      developing nervous system. Recent studies indicated that Wnt signaling modulates
      long term potentiation in adult hippocampal slices. We report here that different
      Wnt ligands are present in hippocampal neurons of rat embryo and adult rat,
      including Wnt-4, -5a, -7a, and -11. Wnt-7a acts as a canonical Wnt ligand in rat
      hippocampal neurons, stimulates clustering of presynaptic proteins, and induces
      recycling and exocytosis of synaptic vesicles as studied by FM dyes. Wnt-3a has a
      moderate effect on recycling of synaptic vesicles, and no effect of Wnt-1 and Wnt
      5a was detected. Electrophysiological analysis on adult rat hippocampal slices
      indicates that Wnt-7a, but not Wnt-5a, increases neurotransmitter release in CA3
      CA1 synapses by decreasing paired pulse facilitation and increasing the miniature
      excitatory post-synaptic currents frequency. These results indicate that the
      presynaptic function of rat hippocampal neurons is modulated by the canonical Wnt
      signaling.

PMID- 18096706
TI  - Voltage gating at the selectivity filter of the Ca2+ release-activated Ca2+
      channel induced by mutation of the Orai1 protein.
AB  - The Ca(2+) release-activated Ca(2+) (CRAC) channel is a plasma membrane (PM)
      channel that is uniquely activated when free Ca(2+) level in the endoplasmic
      reticulum (ER) is substantially reduced. Several small interfering RNA screens
      identified two membrane proteins, Orai1 and STIM1, to be essential for the CRAC
      channel function. STIM1 appears to function in the PM and as the Ca(2+) sensor in
      the ER. Orai1 is forming the pore of the CRAC channel. Despite the recent
      breakthroughs, a mechanistic understanding of the CRAC channel gating is still
      lacking. Here we reveal new insights on the structure-function relationship of
      STIM1 and Orai1. Our data suggest that the cytoplasmic coiled-coil region of
      STIM1 provides structural means for coupling of the ER membrane to the PM to
      activate the CRAC channel. We mutated two hydrophobic residues in this region to
      proline (L286P/L292P) to introduce a kink in the first alpha-helix of the coiled
      coil domain. This STIM1 mutant caused a dramatic inhibition of the CRAC channel
      gating compared with the wild type. Structure-function analysis of the Orai1
      protein revealed the presence of intrinsic voltage gating of the CRAC channel. A
      mutation of Orai1 (V102I) close to the selectivity filter modified CRAC channel
      voltage sensitivity. Expression of the Orai1(V102I) mutant resulted in slow
      voltage gating of the CRAC channel by negative potentials. The results revealed
      that the alteration of Val(102) develops voltage gating in the CRAC channel. Our
      data strongly suggest the presence of a novel voltage gating mechanism at the
      selectivity filter of the CRAC channel.

PMID- 18096707
TI  - An essential role for fibronectin extra type III domain A in pulmonary fibrosis.
AB  - RATIONALE: Tissue fibrosis is considered a dysregulated wound-healing response.
      Fibronectin containing extra type III domain A (EDA) is implicated in the
      regulation of wound healing. EDA-containing fibronectin is deposited during wound
      repair, and its presence precedes that of collagen. OBJECTIVES: To investigate
      the role of EDA-containing fibronectin in lung fibrogenesis. METHODS: Primary
      lung fibroblasts from patients with idiopathic pulmonary fibrosis or from
      patients undergoing resection for lung cancer were assessed for EDA-containing
      fibronectin and alpha-smooth muscle actin (alpha-SMA) expression. Mice lacking
      the EDA domain of fibronectin and their wild-type littermates were challenged
      with the bleomycin model of lung fibrosis. Primary lung fibroblasts from these
      mice were assayed in vitro to determine the contribution of EDA-containing
      fibronectin to fibroblast phenotypes. MEASUREMENTS AND MAIN RESULTS: Idiopathic
      pulmonary fibrosis lung fibroblasts produced markedly more EDA-containing
      fibronectin and alpha-SMA than control fibroblasts. EDA-null mice failed to
      develop significant fibrosis 21 days after bleomycin challenge, whereas wild-type
      controls developed the expected increase in total lung collagen. Histologic
      analysis of EDA-null lungs after bleomycin showed less collagen and fewer alpha
      SMA-expressing myofibroblasts compared with that observed in wild-type mice.
      Failure to develop lung fibrosis in EDA-null mice correlated with diminished
      activation of latent transforming growth factor (TGF)-beta and decreased lung
      fibroblast responsiveness to active TGF-beta in vitro. CONCLUSIONS: The data show
      that EDA-containing fibronectin is essential for the fibrotic resolution of lung
      injury through TGF-beta activation and responsiveness, and suggest that EDA
      containing fibronectin plays a critical role in tissue fibrogenesis.

PMID- 18096708
TI  - Use of procalcitonin to shorten antibiotic treatment duration in septic patients:
      a randomized trial.
AB  - RATIONALE: The duration of antibiotic therapy in critically ill patients with
      sepsis can result in antibiotic overuse, increasing the risk of developing
      bacterial resistance. OBJECTIVES: To test the hypothesis that an algorithm based
      on serial measurements of procalcitonin (PCT) allows reduction in the duration of
      antibiotic therapy compared with empirical rules, and does not result in more
      adverse outcomes in patients with severe sepsis and septic shock. METHODS: In
      patients randomly assigned to the intervention group, antibiotics were stopped
      when PCT levels had decreased 90% or more from the initial value (if clinicians
      agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5
      (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians
      decided on the duration of antibiotic therapy based on empirical rules.
      MEASUREMENTS AND MAIN RESULTS: Patients assigned to the PCT group had 3.5-day
      shorter median duration of antibiotic therapy for the first episode of infection
      than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom
      a decision could be taken based on serial PCT measurements, PCT guidance resulted
      in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68,
      P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar
      mortality and recurrence of the primary infection were observed in PCT and
      control groups. A 2-day shorter intensive care unit stay was also observed in
      patients assigned to the PCT group (P = 0.03). CONCLUSIONS: Our results suggest
      that a protocol based on serial PCT measurement allows reducing antibiotic
      treatment duration and exposure in patients with severe sepsis and septic shock
      without apparent harm.

PMID- 18096709
TI  - TREM-1 expression in tumor-associated macrophages and clinical outcome in lung
      cancer.
AB  - RATIONALE: Triggering receptor expressed on myeloid cells (TREM)-1 is a molecule
      crucial for the triggering and amplification of inflammatory response and a new
      biomarker for sepsis. Tumor-associated macrophages and inflammation in the tumor
      microenvironment are also involved in cancer progression. OBJECTIVES: To
      determine the role of TREM-1 in tumor-associated macrophage and cancer
      progression. METHODS: Using ELISA and Western blot, we measured soluble TREM-1
      levels in 65 pleural effusions of various etiologies. We evaluated TREM-1
      positive cells by immunocytochemistry in malignant pleural effusion and in lung
      tumor versus adjacent normal tissue in surgical specimens from 68 patients with
      non-small cell lung cancer (NSCLC). TREM-1 expression was correlated with patient
      survival. TREM-1 expression in primary isolated peripheral blood macrophages
      cocultured with lung cancer cell lines was determined by quantitative real-time
      reverse transcriptase-polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS:
      Soluble TREM-1 and tumor-associated macrophage TREM-1 expression was increased in
      malignant pleural effusions in patients with NSCLC. Lung cancer cells could
      directly up-regulate TREM-1 and proinflammatory cytokine (tumor necrosis factor
      alpha, IL-1beta) expression in primary isolated peripheral blood macrophages in
      coculture experiments. Increased TREM-1-positive tumor-associated macrophages in
      tumor tissue of patients with NSCLC were associated with reduced disease-free (P
      = 0.011) and overall survival (P = 0.004). Multivariate Cox regression analysis
      indicated that TREM-1 was an independent predictor of patient survival (hazard
      ratio, 2.72; 95% confidence interval, 1.33-5.57; P = 0.006). CONCLUSIONS: Cancer
      cells can directly up-regulate TREM-1 expression in patients' macrophages. TREM-1
      expression in tumor-associated macrophages is associated with cancer recurrence
      and poor survival of patients with NSCLC. TREM-1 and the inflammatory response
      may play an important role in cancer progression.

PMID- 18096710
TI  - Allergen induces the migration of platelets to lung tissue in allergic asthma.
AB  - RATIONALE: Platelets are essential for pulmonary leukocyte recruitment, airway
      hyperresponsiveness, and bronchial remodeling in animals with allergic
      inflammation and can be found in bronchoalveolar lavage of sensitized animals. No
      studies, however, have explored the direct migration of platelets to lungs.
      OBJECTIVES: To assess whether platelets migrate into lung parenchyma in response
      to inhaled allergen in ovalbumin-sensitized mice; to assess the role of the
      FcepsilonRI receptor in this phenomenon; and to evaluate whether platelets from
      patients with asthma, or from sensitized mice, undergo chemotaxis in vitro in
      response to relevant antigens. METHODS: Ovalbumin-sensitized wild-type (WT) mice,
      or FcRgamma(-/-) mice lacking the FcepsilonRIgamma, were challenged with
      aerosolized allergen and lungs analyzed by platelet-specific
      immunohistochemistry. In some experiments, mice were depleted of platelets and
      cross-transfused with either WT or FcRgamma(-/-) platelets to assess the role of
      platelet FcRgamma(-/-). Chemotaxis of platelets from patients with asthma or from
      sensitized mice was studied in vitro. MEASUREMENTS AND MAIN RESULTS: Histology of
      lungs revealed isolated platelets, migrating out of vessels and localizing
      underneath the airways after allergen challenge in WT but not in FcRgamma(-/-)
      mice. Platelets from patients with asthma and from sensitized WT mice, but not
      from sensitized FcRgamma(-/-) mice, migrated in vitro toward the relevant
      allergen or an anti-IgE. Platelets from normal mice were found to express
      FcepsilonRIgamma and platelet-bound IgEs were increased in sensitized mice.
      CONCLUSIONS: Platelets migrate extravascularly in response to a sensitizing
      allergen via a mechanism dependent on the interaction among allergen, allergen
      specific IgE, and the FcepsilonRI, and this may allow them to participate
      directly in allergic tissue inflammation.

PMID- 18096711
TI  - A bad bug takes on a new role as a cause of ventilator-associated pneumonia.

PMID- 18096712
TI  - Bronchoalveolar cellular analysis in scleroderma lung disease: does Sutton's law
      hold?

PMID- 18096713
TI  - On treatment outcomes of patients with HIV and tuberculosis.

PMID- 18096714
TI  - Muscle atrophy and hypertrophy signaling pathways in COPD: a role in muscle
      remodeling?

PMID- 18096715
TI  - Challenges to the withdrawal of care in critically ill patients in India.

PMID- 18096716
TI  - Families and the decision to withhold or withdraw life-sustaining therapy from
      the critically ill: are pressure tactics ever justified?

PMID- 18096717
TI  - Prion detection by an amyloid seeding assay.
AB  - Polymerization of recombinant prion protein (recPrP), which was produced in
      bacteria, into amyloid fibers was accompanied by the acquisition of prion
      infectivity. We report here that partially purified preparations of prions seed
      the polymerization of recPrP into amyloid as detected by a fluorescence shift in
      the dye Thioflavin T. Our amyloid seeding assay (ASA) detected PrP(Sc), the sole
      component of the prion, in brain samples from humans with sporadic Creutzfeldt
      Jakob disease, as well as in rodents with experimental prion disease. The ASA
      detected a variety of prion strains passaged in both mice and hamsters. The
      sensitivity of the ASA varied with strain type; for hamster Sc237 prions, the
      limit of detection was approximately 1 fg. Some prion strains consist largely of
      protease-sensitive PrP(Sc) (sPrP(Sc)), and these strains were readily detected by
      ASA. Our studies show that the ASA provides an alternative methodology for
      detecting both sPrP(Sc) and protease-resistant PrP(Sc) that does not rely on
      protease digestion or immunodetection.

PMID- 18096718
TI  - The relationship between medical practice characteristics and quality of care for
      cardiovascular disease.
AB  - The settings in which health care services are delivered have the potential to
      influence the quality of health care services in numerous ways, but little is
      known about the relationship between characteristics of medical practices and
      quality of care. In this study, the authors studied patients with coronary heart
      disease (CHD). The authors surveyed 225 medical practices in 2000 and 2001 and
      obtained information on quality measures from the medical records for more than
      1,600 of their patients with CHD. Results suggest that quality of care, at least
      for common conditions with agreed-on measures, is not strongly influenced by
      financial characteristics of medical practices, although there does seem to be
      some relationship with practice structure such as size and quality.

PMID- 18096719
TI  - Unique dielectric properties distinguish stem cells and their differentiated
      progeny.
AB  - The relatively new field of stem cell biology is hampered by a lack of sufficient
      means to accurately determine the phenotype of cells. Cell-type-specific markers,
      such as cell surface proteins used for flow cytometry or fluorescence-activated
      cell sorting, are limited and often recognize multiple members of a stem cell
      lineage. We sought to develop a complementary approach that would be less
      dependent on the identification of particular markers for the subpopulations of
      cells and would instead measure their overall character. We tested whether a
      microfluidic system using dielectrophoresis (DEP), which induces a frequency
      dependent dipole in cells, would be useful for characterizing stem cells and
      their differentiated progeny. We found that populations of mouse neural
      stem/precursor cells (NSPCs), differentiated neurons, and differentiated
      astrocytes had different dielectric properties revealed by DEP. By isolating
      NSPCs from developmental ages at which they are more likely to generate neurons,
      or astrocytes, we were able to show that a shift in dielectric property
      reflecting their fate bias precedes detectable marker expression in these cells
      and identifies specific progenitor populations. In addition, experimental data
      and mathematical modeling suggest that DEP curve parameters can indicate cell
      heterogeneity in mixed cultures. These findings provide evidence for a whole cell
      property that reflects stem cell fate bias and establish DEP as a tool with
      unique capabilities for interrogating, characterizing, and sorting stem cells.

PMID- 18096720
TI  - High-glucose-induced prostaglandin E(2) and peroxisome proliferator-activated
      receptor delta promote mouse embryonic stem cell proliferation.
AB  - Peroxisome proliferator-activated receptor is a nuclear receptor that has been
      implicated in blastocyst implantation, cell cycle, and pathogenesis of diabetes.
      However, the signal cascades underlying this effect are largely unknown in embryo
      stem cells. This study examined whether or not there is an association between
      the reactive oxygen species-mediated prostaglandin E(2) (PGE(2))/peroxisome
      proliferator-activated receptor (PPAR) delta and the growth response to high
      glucose levels in mouse ESCs. A high concentration of glucose (25 mM)
      significantly increased the level of [3H]thymidine incorporation, the level of 5
      bromo-2'-deoxyuridine incorporation, and the number of cells. Moreover, 25 mM
      glucose increased the intracellular reactive oxygen species, phosphorylation of
      the cytosolic phospholipase A(2) (cPLA(2)), and the release of [3H]arachidonic
      acid ([3H]AA). In addition, 25 mM glucose also increased the level of
      cyclooxygenase-2 (COX-2) protein expression, which stimulated the synthesis of
      PGE(2). Subsequently, high glucose-induced PGE(2) stimulated PPARdelta expression
      directly or through Akt phosphorylation indirectly through the E type
      prostaglandin receptor receptors. The PPARdelta antagonist inhibited the 25 mM
      glucose-induced DNA synthesis. Moreover, transfection with a pool of PPARdelta
      specific small interfering RNA inhibited the 25 mM glucose-induced DNA synthesis
      and G1/S phase progression. Twenty-five millimolar glucose also increased the
      level of the cell cycle regulatory proteins (cyclin E/cyclin-dependent kinase
      [CDK] 2 and cyclin D1/CDK 4) and decreased p21(WAF1/Cip1) and p27(Kip1), which
      were blocked by the inhibition of the cPLA(2), COX-2, or PPARdelta pathways. In
      conclusion, high glucose promotes mouse ESC growth in part through the cPLA(2)
      mediated PGE(2) synthesis and in part through PPARdelta pathways.

PMID- 18096721
TI  - Tex19, a mammalian-specific protein with a restricted expression in pluripotent
      stem cells and germ line.
AB  - Although the properties of embryonic stem (ES) cells make these cells very
      attractive in the field of replacement therapy, the molecular mechanisms involved
      in the maintenance of their pluripotency are not fully characterized. Starting
      from the observation that most pluripotent markers are also expressed by
      spermatogonia stem cells, we identified Tex19 as a new potential pluripotency
      marker. We show that Tex19 is a mammalian-specific protein duplicated in mouse
      and rat, renamed Tex19.1 and Tex19.2, whereas only one form is found in human. In
      mouse, both forms are localized on chromosome 11 and transcribed in opposite
      directions. Tex19 proteins are well conserved, showing two highly conserved
      domains that do not present any similarity with any other known domains. We show
      that Tex19.2 is specifically detected in the male somatic gonad lineage, whereas
      Tex19.1 expression is very similar to that of Oct4. Transcripts are maternally
      inherited, and expression starts as soon as the early embryo and later is limited
      to the germ line. Tex19.1 transcripts were also detected in mouse pluripotent
      stem cells, and expression of Tex19.1, like that of Oct4, decreases after murine
      embryonic stem and germ cell differentiation. Human TEX19 was more closely
      related to murine Tex19.1 and was also detected in adult testis and in
      undifferentiated ES cells. By immunofluorescence, we found that Tex19.1 protein
      localizes to the nucleus of mouse ES and inner cell mass cells. All these results
      suggest that Tex19.1, as well as human TEX19, could be a new factor involved in
      the maintenance of self-renewal or pluripotency of stem cells.

PMID- 18096722
TI  - The stem cell marker prominin-1/CD133 on membrane particles in human
      cerebrospinal fluid offers novel approaches for studying central nervous system
      disease.
AB  - Cerebrospinal fluid (CSF) is routinely used for diagnosing and monitoring
      neurological diseases. The CSF proteins used so far for diagnostic purposes
      (except for those associated with whole cells) are soluble. Here, we show that
      human CSF contains specific membrane particles that carry prominin-1/CD133, a
      neural stem cell marker implicated in brain tumors, notably glioblastoma.
      Differential and equilibrium centrifugation and detergent solubility analyses
      showed that these membrane particles were similar in physical properties and
      microdomain organization to small membrane vesicles previously shown to be
      released from neural stem cells in the mouse embryo. The levels of membrane
      particle-associated prominin-1/CD133 declined during childhood and remained
      constant thereafter, with a remarkably narrow range in healthy adults.
      Glioblastoma patients showed elevated levels of membrane particle-associated
      prominin-1/CD133, which decreased dramatically in the final stage of the disease.
      Hence, analysis of CSF for membrane particles carrying the somatic stem cell
      marker prominin-1/CD133 offers a novel approach for studying human central
      nervous system disease.

PMID- 18096723
TI  - Insulin redirects differentiation from cardiogenic mesoderm and endoderm to
      neuroectoderm in differentiating human embryonic stem cells.
AB  - Human embryonic stem cells (hESC) can proliferate indefinitely while retaining
      the capacity to form derivatives of all three germ layers. We have reported
      previously that hESC differentiate into cardiomyocytes when cocultured with a
      visceral endoderm-like cell line (END-2). Insulin/insulin-like growth factors and
      their intracellular downstream target protein kinase Akt are known to protect
      many cell types from apoptosis and to promote proliferation, including hESC
      derived cardiomyocytes. Here, we show that in the absence of insulin, a threefold
      increase in the number of beating areas was observed in hESC/END-2 coculture. In
      agreement, the addition of insulin strongly inhibited cardiac differentiation, as
      evidenced by a significant reduction in beating areas, as well as in alpha
      actinin and beta-myosin heavy chain (beta-MHC)-expressing cells. Real-time
      reverse transcription-polymerase chain reaction and Western blot analysis showed
      that insulin inhibited cardiomyogenesis in the early phase of coculture by
      suppressing the expression of endoderm (Foxa2, GATA-6), mesoderm (brachyury T),
      and cardiac mesoderm (Nkx2.5, GATA-4). In contrast to previous reports, insulin
      was not sufficient to maintain hESC in an undifferentiated state, since
      expression of the pluripotency markers Oct3/4 and nanog declined independently of
      the presence of insulin during coculture. Instead, insulin promoted the
      expression of neuroectodermal markers. Since insulin triggered sustained
      phosphorylation of Akt in hESC, we analyzed the effect of an Akt inhibitor during
      coculture. Indeed, the inhibition of Akt or insulin-like growth factor-1 receptor
      reversed the insulin-dependent effects. We conclude that in hESC/END-2
      cocultures, insulin does not prevent differentiation but favors the
      neuroectodermal lineage at the expense of mesendodermal lineages.

PMID- 18096724
TI  - Intraobserver and interobserver reproducibility of 3-dimensional power Doppler
      vascular indices in assessment of solid and cystic-solid adnexal masses.
AB  - OBJECTIVE: The purpose of this study was to assess the intraobserver and
      interobserver reproducibility of 3-dimensional (3D) power Doppler angiography
      derived vascular indices in evaluation of vascularized solid and cystic-solid
      adnexal masses. METHODS: Stored 3D power Doppler angiographic volume data from 12
      consecutive women with a diagnosis of a complex adnexal mass (6 cystic-solid and
      6 solid) evaluated and treated at our institution were retrieved from our
      database for analysis. Two examiners performed the calculations blinded to each
      other. Calculations were performed offline in a computer using Virtual Organ
      Computer-Aided Analysis software (plane A, 9 degrees rotation step) to assess
      volume and vascularization (vascularization index, flow index, and
      vascularization-flow index) from solid areas within the tumor. In all cases, a
      definitive histologic diagnosis was obtained. Intraobserver and interobserver
      reproducibility was assessed by calculating the intraclass and interclass
      correlation coefficients for each index. RESULTS: All tumors proved to be
      malignant after surgical removal. Intraobserver reproducibility for both
      examiners and interobserver reproducibility were high for all indices (interclass
      correlation coefficient > 0.95). CONCLUSIONS: Three-dimensional power Doppler
      angiography is a reproducible technique for offline assessment of stored 3D
      volume data of vascularized adnexal masses.

PMID- 18096725
TI  - Preoperative sonographic and clinical characteristics as predictors of ovarian
      torsion.
AB  - OBJECTIVE: The purpose of this study was to determine the most closely associated
      sonographic and clinical characteristics of ovarian torsion. METHODS: The medical
      records and sonographic studies of 39 patients with pathologically proven ovarian
      torsion diagnosed at our institution from July 1, 2000, through December 31,
      2005, were retrospectively reviewed. The volumes of the affected ovaries and
      ovary/mass complexes were compared with an age-appropriate standard. Statistical
      significance of the data was assessed by a likelihood ratio chi(2) analysis.
      RESULTS: All patients (100%) had a chief symptom of abdominal pain. Thirty-three
      (85%) reported vomiting; 22 (56%) had leukocytosis; and 7 (18%) had a documented
      elevated temperature. All affected ovaries and ovary/mass complexes were
      enlarged. Twenty-one (54%) had arterial flow on Doppler interrogation, and 18
      (46%) had no arterial flow. Thirteen (33%) had venous flow, and 26 (67%) had no
      venous flow. Differences in the arterial and venous flow patterns between the
      premenarchal and reproductive age groups were not statistically significant.
      CONCLUSIONS: Abdominal pain, vomiting, ovarian enlargement, and absence of
      ovarian venous Doppler flow are the most frequently shown clinical and
      sonographic indicators of ovarian torsion. However, ovarian enlargement, even in
      the presence of arterial and venous Doppler flow, is the most commonly associated
      sonographic finding. Suspicion of ovarian torsion should be high in the setting
      of clinical symptoms and ovarian enlargement regardless of the presence or
      absence of an ovarian Doppler signal.

PMID- 18096726
TI  - Stereoscopic evaluation of fetal bony structures.
AB  - OBJECTIVE: The purpose of this study was to assess the performance of
      stereoscopic compared with conventional viewing of 3-dimensional ultrasound
      (3DUS) data for evaluation of fetal bony structures. METHODS: A series of 47
      human fetuses were evaluated with conventional 3DUS scanning systems. Twenty-five
      volumes of the fetal head, thorax, and abdomen were acquired. Volume-rendered
      images of the fetal cranium and spine were displayed interactively on a real-time
      stereoscopic graphics workstation. Visualization parameters were interactively
      optimized. Both conventional and stereoscopic images were evaluated for the
      clarity of structure visualization (0, nonvisualized; 1, nondiagnostic; 2,
      adequate; and 3, excellent), the ability to identify key anatomic landmarks (eg,
      sutures, palate, vertebrae, and ribs), artifacts, and evaluation time. RESULTS:
      Fetal bony structures, especially high-contrast structures, were readily
      identified with both conventional and stereoscopic. Overall, stereoscopic viewing
      provided a statistically significant improvement compared with conventional
      viewing (P < .01), improved conspicuity of complex bony structures, and added
      structural detail information that assisted in identification of complex anatomy
      in 14% of the fetal skull and 26% of the fetal spine cases. Overlapping
      structures were better identified on the volume-rendered stereoscopic display,
      with stereoscopic viewing improving differentiation of near and far structures.
      An interactive display and inclusion of a planar slice review further assisted in
      identification of structures. The evaluation times were comparable for the two
      methods. CONCLUSIONS: The stereoscopic display of rendered 3DUS data adds
      valuable information that assists in identification of fetal bony structures,
      such as cranial sutures and spinal vertebrae, particularly in complex formations.
      The increasing availability of stereoscopic visualization workstations will offer
      an additional tool for fetal diagnosis and evaluation.

PMID- 18096727
TI  - Columns of the fornix, not to be mistaken for the cavum septi pellucidi on
      prenatal sonography.
AB  - OBJECTIVE: Visualization of the cavum septi pellucidi (CSP) is considered an
      integral part of the prenatal second-and third-trimester sonographic evaluations
      of the fetal neural axis. We have noted that another anatomic structure, the
      columns of the fornix, can be mistaken for the CSP and result in the missed
      diagnosis of agenesis of the corpus callosum. METHODS: We describe a case in
      which the columns of the fornix were misinterpreted as representing the CSP
      during a sonographic evaluation at 18 weeks' gestation. After a follow-up
      sonogram at 35 weeks, agenesis of the corpus callosum was detected. A
      retrospective evaluation of the prevalence of forniceal columns was then
      performed in 100 consecutive sonograms of pregnancies between 18 and 24 weeks'
      gestation. A prospective study was then performed in 20 patients to determine the
      prevalence of visualization of the columns of the fornix. RESULTS: In 86 of 100
      patients, the columns of the fornix were retrospectively identified as discrete
      and separate structures from the CSP. When additional views were obtained
      prospectively in the forebrain, the fornix could be identified in all 20
      patients. CONCLUSIONS: The columns of the fornix may simulate the appearance of
      the CSP on second- and third-trimester sonograms. The distinction between these
      structures can be made because the columns of the fornix will show a linear
      reflection (3 lines) at their interface, whereas the CSP will appear as a fluid
      filled triangular or rectangular fluid-filled space without a central line.

PMID- 18096728
TI  - Supratentorial abnormalities in the Chiari II malformation, I: the ventricular
      "point".
AB  - OBJECTIVE: The sonographic diagnosis of fetal myelomeningocele has improved
      dramatically over the past 20 years, mainly because the diagnostic focus has
      shifted from observation of the spinal abnormality to observation of cranial
      abnormalities. We describe an abnormality in the shape of the occipital horn that
      has received scant attention in the sonographic literature. The abnormality is a
      misshapen occipital horn that is "pointed" rather than rounded. This study
      analyzed the frequency of this observation and technical aspects that improve its
      visualization. METHODS: From a database of obstetric sonograms, we searched for
      all cases in which open fetal myelomeningocele was sonographically detected. The
      search covered the period from 1999 to 2007. We then retrospectively reviewed the
      fetal intracranial findings in each case, with special attention to the contour
      of the occipital horn of the lateral ventricle. RESULTS: A total of 89 fetuses
      were identified. The mean and median gestational ages were 22 weeks 4 days and 22
      weeks 2 days, respectively. Of the 89 cases, 62 (70%) had an occipital horn with
      a pointed shape. This abnormality was better seen in cases judged to be well
      visualized and in cases in which digital video clips were available for review.
      The abnormality was more frequently seen in fetuses at less than 24 weeks'
      gestation and in fetuses without ventriculomegaly. Finally, it was seen as
      commonly among fetuses with mild posterior fossa deformations as in those with
      more severe distortions. CONCLUSIONS: The occipital point is a common
      supratentorial feature of the Chiari II malformation. It is seen more commonly in
      fetuses at less than 24 weeks and in fetuses with normal-sized ventricles. As
      well, it is seen as commonly among fetuses with mild posterior fossa deformations
      as in those with more severe distortions. Therefore, its usefulness is enhanced
      as an observation in the armamentarium of cranial findings for detection of fetal
      myelomeningocele.

PMID- 18096729
TI  - Predicting macrosomia.
AB  - OBJECTIVE: The purpose of this study was to evaluate the prediction of fetal
      macrosomia based on ultrasound estimates of fetal weight and amniotic fluid
      volume combined with clinical risk factors. METHODS: A retrospective cohort study
      of women undergoing indicated obstetric ultrasound examinations within 7 days of
      delivery was conducted. RESULTS: A total of 3115 women gave birth within 7 days
      of ultrasound examinations that included an estimated fetal weight (EFW) and an
      amniotic fluid index (AFI). Clinical risk factors were associated with an 8%
      positive predictive value for a birth weight of 4000 g or higher. Adding an
      ultrasound EFW of 4000 g or higher increased the positive predictive value to
      62%. Adding an AFI of 20 cm or higher to the clinical risk factors and the
      ultrasound EFW further increased the positive predictive value to 71%.
      CONCLUSIONS: An ultrasound EFW of 4000 g or higher within 1 week of delivery
      combined with clinical risk factors and an increased AFI is associated with
      macrosomia at birth in 71% of cases.

PMID- 18096730
TI  - Detection of bladder tumors with 3-dimensional sonography and virtual sonographic
      cystoscopy.
AB  - OBJECTIVE: Bladder tumors are among the most common types of malignant neoplasms
      of the urinary tract. The purpose of this study was to evaluate the potential
      value of 3-dimensional (3D) sonography and sonographic cystoscopy in detection of
      bladder tumors. METHODS: Thirty-one patients with suspected or known bladder
      tumors were included this study. All patients underwent 3D sonography and
      conventional cystoscopy within 15 days. The number, size, location, and
      morphologic features of the lesions were evaluated on gray scale, 3D virtual, and
      multiplanar reconstruction images obtained from the patients. The results of 3D
      sonographic cystoscopy were compared with the findings from conventional
      cystoscopy, which was considered the reference standard. RESULTS: Twenty-eight
      (90.3%) of 31 3D virtual sonographic cystoscopic studies had good or excellent
      image quality. Conventional cystoscopy revealed 47 lesions in 22 of 28 patients;
      3D sonographic virtual cystoscopy showed 41 (87.2%) of 47 lesions. Three
      dimensional virtual sonography alone had sensitivity of 96.2%, specificity of
      70.6%, a positive predictive value of 93.9%, and a negative predictive value of
      80% for tumor detection. The combination of gray scale sonography, multiplanar
      reconstruction, and 3D virtual sonography had sensitivity of 96.4%, specificity
      of 88.8%, a positive predictive value of 97.6%, and a negative predictive value
      of 84.2% for tumor detection. CONCLUSIONS: Three-dimensional sonography is a
      promising alternative noninvasive technique for use in detection of bladder
      tumors, their localization, and perivesical spreading. The location, size, and
      morphologic features of the tumors shown on 3D sonography agreed well with the
      findings of conventional cystoscopy.

PMID- 18096731
TI  - Study of the synergistic effect on hepatoma 22 tumor cells by focused ultrasound
      activation of hematoporphyrin.
AB  - OBJECTIVE: The synergistic effect of ultrasound and drugs on tumor cells is known
      as sonodynamic therapy (SDT). The purpose of this study was to evaluate the
      effects of SDT on lipid peroxidation and the activity of antioxidative enzymes in
      isolated hepatoma 22 (H-22) cells to better understand the bioeffects of SDT.
      METHODS: The viability of cells was evaluated by the Trypan blue dye exclusion
      test. The morphologic changes of H-22 cells were observed by a scanning electron
      microscope immediately after treatment. The intracellular reactive oxygen species
      levels were detected by 2',7'-dichlorofluorescein diacetate. Colorimetry and
      enzymatic chemical methods were used to measure the lipid peroxidation levels and
      activities of key antioxidant enzymes (ie, superoxide dismutase, selenium
      dependent glutathione peroxidase, and catalase) in H-22 tumor cells. RESULTS: Our
      experiments indicated that the ultrasonically induced cell damage rate was
      increased with 100-microg/mL hematoporphyrin, whereas no cell damage was observed
      with hematoporphyrin alone. Generation of reactive oxygen species in cell
      suspensions after SDT treatment was remarkably higher than in controls. The
      malondialdehyde content was remarkably enhanced, and antioxidative enzyme
      activities were obviously decreased compared with controls. CONCLUSIONS: This
      study suggests that oxygen free radicals may play an important role in improving
      membrane lipid peroxidation and decreasing the activities of key antioxidant
      enzymes in cells. It was speculated that this biological mechanism might be
      involved in mediating the killing effect of H-22 cells in SDT.

PMID- 18096732
TI  - Factors affecting the efficacy of ultrasound-guided vacuum-assisted percutaneous
      excision for removal of benign breast lesions.
AB  - OBJECTIVE: This study was designed to evaluate the effectiveness of complete
      removal and factors affecting the presence of a residual mass and complications
      after ultrasound-guided vacuum-assisted percutaneous removal of benign breast
      lesions. METHODS: We retrospectively evaluated ultrasound images and medical
      records of 263 breast masses from 199 patients that were removed with an
      ultrasound-guided vacuum-assisted device. All lesions were assumed as benign on
      ultrasound imaging or had been confirmed as benign by a previous core needle
      biopsy. The influence of the size, distance from the nipple, number of lesions
      removed at a time, and pathologic diagnosis of all of the removed masses on the
      completeness of the removal and the presence of complications was analyzed. The
      Mann-Whitney U test was used in the statistical analysis. RESULTS: The complete
      removal rate for ultrasound imaging immediately after the procedure was 95.8%,
      and the rate at more than 6 months for follow-up ultrasound imaging was 92.3%.
      Larger lesions, lesions closer to the nipple, and cases in which multiple lesions
      were removed at a time showed the presence of more residual lesions. Lesions
      closer to the nipple and cases in which multiple lesions were removed
      simultaneously developed more hematomas (P < .05). CONCLUSIONS: Ultrasound-guided
      vacuum-assisted percutaneous excision showed high effectiveness for the removal
      of benign breast masses. However, more attention should be given to certain
      lesions to increase the efficacy.

PMID- 18096733
TI  - Sonographic differentiation of benign and malignant papillary lesions of the
      breast.
AB  - OBJECTIVE: The purpose of this study was to evaluate sonographic findings of
      breast papillary lesions and the effectiveness of the American College Radiology
      Breast Imaging Reporting and Data System sonographic assessment system for
      differentiation of benign and malignant papillary lesions. METHODS: We
      retrospectively reviewed breast sonographic findings of 46 surgically proven
      benign papillomas and 22 papillary carcinomas. All sonographic images of patients
      were interpreted by 2 radiologists. Sonographic findings were analyzed according
      to the Breast Imaging Reporting and Data System classification. RESULTS: The
      shape of the lesion was round or oval in 33 benign lesions (71.7%) and 13
      papillary carcinomas (61.9%). As for the margin, a circumscribed margin was found
      in 31 benign papillomas (67.4%) and 12 malignant lesions (57.1%). Differences in
      the predominant shape and margin between the 2 groups were not statistically
      significant (P > .05). Fourteen benign papillomas (30.5%) and 12 papillary
      carcinomas (57.1%) showed a complex echo pattern. It was more frequently observed
      in malignant lesions; however, it was not statistically significant (P = .09). A
      nonparallel orientation, an echogenic halo, posterior acoustic enhancement, and
      associated microcalcification were more frequently found in malignant than in
      benign lesions (P < .05). When the presence of any suspicious sonographic feature
      (nonparallel orientation, echogenic halo, posterior enhancement, or
      calcification) was considered to indicate malignancy, interpretation of the
      sonographic features gave sensitivity of 85.7%, specificity of 64.9%, a positive
      predictive value of 47.4%, and a negative predictive value of 92.5% for detection
      of malignant papillary lesions. The only differential finding between noninvasive
      and invasive papillary cancers was a circumscribed margin (P < .05). CONCLUSIONS:
      Sonographic features more specific to malignancy include a nonparallel
      orientation, an echogenic halo, posterior acoustic enhancement, and associated
      microcalcification.

PMID- 18096734
TI  - Influence of physiologic cardiac hypertrophy on the prevalence of heart valve
      regurgitation.
AB  - OBJECTIVE: Chronic dynamic exercise leads to regulative and structural
      adaptations of the heart (athlete's heart). To what extent the enlargement and
      physiologic hypertrophy of the heart lead to changes in the function of the
      valves, particularly regurgitation, is not yet clear. The aim of this study was
      to examine the regurgitation levels of different states of "athlete's heart."
      METHODS: Our study population consisted of 5124 healthy subjects (4046 male and
      1078 female, 18-60 years), regularly exercising 1 to 20 h/wk. Subjects were
      divided into 3 groups depending on their relative heart volumes (RHVs): (1) very
      enlarged heart group (VEHG; male, n = 1251; female, n = 201), with RHVs of
      greater than 14 (male) and 13 (female) mL/kg; (2) mildly enlarged heart group
      (MEHG; male, n = 702; female, n = 224), with RHVs of 12 to 14 (male) and 11 to 13
      (female) mL/kg; and (3) control subjects (CS; male, n = 2093; female, n = 653),
      with RHVs of less than 12 (male) and 11 (female) mL/kg. RESULTS: According to US
      Food and Drug Administration criteria for valve regurgitation, it could be shown
      by Doppler sonography that as physiologic enlargement and hypertrophy increased
      significantly, the frequency and severity of aortic valve regurgitation (mean +/-
      SD: VEHG, 0.04 +/- 0.09; MEHG, 0.09 +/- 0.10; CS, 0.10 +/- 0.11; P < .05) and
      high mitral regurgitation (VEHG, 0.10 +/- 0.17; MEHG, 0.20 +/- 0.29; CS, 0.26 +/-
      0.32; P < .01) decreased. On the contrary, pulmonary regurgitation (VEHG, 0.79 +/
      0.45; MEHG, 0.47 +/- 0.33; CS, 0.35 +/- 0.38; P < .01) and tricuspid valve
      regurgitation (VEHG, 0.42 +/- 0.29; MEHG, 0.47 +/- 0.33; CS, 0.35 +/- 0.38; P <
      .01) increased highly significantly with heart size. CONCLUSIONS: These findings
      strongly support the view of athlete's heart as a physiologic adaptation of the
      heart, at least on the left side, not causing increased valvular regurgitation.

PMID- 18096735
TI  - Sonographic evaluation of vascular injuries.
AB  - OBJECTIVE: The purpose of this presentation is to highlight the color Doppler
      duplex sonographic features of procedure-related and blunt or penetrating trauma
      related vascular injuries. METHODS: Different kinds of vascular complications
      such as pseudoaneurysms, arteriovenous fistulas, dissection, and thrombosis are
      discussed. Cases of vascular injuries in the extremities, neck, and abdomen are
      presented to illustrate the spectrum of sonographic appearances. RESULTS: Color
      Doppler duplex sonography is valuable in the diagnosis and monitoring of most
      vessel injuries and in the treatment of pseudoaneurysms. It is useful for flow
      analysis and for follow-up after treatment. However, because of limitations
      inherent to sonography, such as bones, air, casts, skin burns, and relatively
      slow performance of the test, magnetic resonance imaging, computed tomography,
      and angiography are necessary for further evaluation in selected cases.
      CONCLUSIONS: Color Doppler duplex sonography is a widely available, noninvasive,
      and accurate technique for evaluating vascular injuries and should be the first
      line imaging modality in most patients.

PMID- 18096736
TI  - A review of findings in fetal cardiac section drawings. Part 3: the 3-vessel
      trachea view and variants.
AB  - OBJECTIVE: The goal of this presentation is to review some of the common and rare
      fetal heart abnormalities and to provide an easy approach to these findings with
      the schematic drawings. METHODS: Over the past 10 years, we collected cases in
      which the common views of the heart were abnormal and the differential diagnoses
      that existed for each. This presentation shows the normal sonographic sections
      and then variations of these sections and the associated anomalies. We used
      illustrative drawings to present these findings, enabling us to point out the
      main sonographic features of abnormalities of the heart. RESULTS: This work
      reviews 21 fetal heart abnormalities in schematic drawings. CONCLUSIONS: This
      short review highlights several of the anomalies that can be recognized on the
      common sonographic views. The drawings tend to simplify the findings but should
      serve as a basis for those doing fetal echocardiography when they encounter an
      unusual finding.

PMID- 18096737
TI  - Three-dimensional sonographic evaluations of embryonic brain development.
AB  - OBJECTIVE: The purpose of this presentation is to show 3-dimensional development
      of the ventricles of the brain in early pregnancy, from 6 to 13 weeks, and to
      provide a reference for early diagnosis of central nervous system anomalies such
      as hydrocephalus and holoprosencephaly. METHODS: From March 2007 to August 2007,
      46 patients were included. All patients had routine first-trimester 2- and 3
      dimensional sonographic examinations at the same time. All cases were examined
      with a Voluson 730 Expert or Voluson E8 ultrasound scanner (GE Healthcare,
      Milwaukee, WI) using a 4- to 8- or 6- to 12-MHz transvaginal probe. Volumes were
      reviewed and analyzed with GE 4DView release 6 software. After the inversion
      rendering mode was selected, volumes were dissected by the MagicCut function to
      show the ventricles. RESULTS: A total of 34 volumes from 7 to 12 complete
      gestational weeks were successfully dissected. Those before 7 and after 12 weeks
      could not be dissected properly. The crown-rump length ranged from 12.7 to 68 mm.
      Twelve representative images of the rendered volumes in chronologic order are
      shown. The brain volume dissections of 2 fetuses with ventriculomegaly and alobar
      holoprosencephaly are shown for comparison. CONCLUSIONS: Early human brain
      ventricular structures could be evaluated in vivo with 3-dimensional sonography.
      This presentation shows the timeline of brain development and provides reference
      images to compare possible anomalies of development.

PMID- 18096738
TI  - Imaging findings of chest wall lesions on breast sonography.
AB  - OBJECTIVE: The purpose of this presentation is to illustrate the sonographic
      findings of chest wall lesions that were depicted on breast sonography. METHODS:
      Chest wall lesions detected during breast sonography were collected and reviewed
      retrospectively. RESULTS: The sonographic findings of normal chest walls and
      various pathologic chest wall lesions, including inflammatory lesions, benign
      neoplasms, and malignant neoplasms, are discussed. CONCLUSIONS: Familiarity with
      normal sonographic anatomy and chest wall lesions could be helpful in
      differentiating a chest wall lesion from a breast lesion and in showing whether
      the origin of any palpable breast lump is in the breast parenchyma or the chest
      wall on breast sonography.

PMID- 18096739
TI  - A convenient sonographic technique for diagnosis of pulsatile tinnitus induced by
      a high jugular bulb.
AB  - OBJECTIVE: The purpose of this report is to describe our experience with
      sonography in a case of pulsatile tinnitus (PT) due to a high jugular bulb (HJB).
      METHODS: A 71-year-old woman came to our hospital with a 1-year history of right
      PT. A right HJB was shown on cerebral angiography, and enlargement of the right
      jugular blub compared with the left side was found. First, the ultrasound probe
      was placed on the anterior right upper neck at the anterior edge of the
      sternocleidomastoid muscle to identify the ipsilateral internal jugular vein
      (IJV) and measure the flow velocity. After the measurement, the ultrasound probe
      gradually compressed the skin until the flow in the IJV decreased. RESULTS: The
      patient reported that her PT decreased after the flow in the IJV decreased. We
      decided that the PT in this case was induced by the HJB. CONCLUSIONS: This
      technique is less invasive and convenient for the diagnosis of PT caused by an
      HJB.

PMID- 18096740
TI  - Color Doppler sonography in evaluation of spermatoceles: the "falling snow" sign.
AB  - OBJECTIVE: Doppler sonography is not commonly used in evaluation of cystic
      lesions with internal echoes. Here we report the use of the mechanical properties
      of color Doppler sonography to further characterize 3 spermatoceles. METHODS:
      Three patients who came to University of California San Francisco Imaging Center
      with painless unilateral scrotal enlargement were evaluated with sonography and
      were found to have large spermatoceles. Color Doppler sonography was applied to
      these spermatoceles, and digital video clips were obtained as the color beam was
      instituted. RESULTS: When color Doppler sonography was applied to each
      spermatocele, the internal echoes moved away from the transducer, resulting in an
      appearance similar to falling snow. CONCLUSIONS: The "falling snow" sign can be
      used to enhance the diagnosis of a spermatocele as well as to evaluate a
      superficial cystic lesion with echogenic fluid and internal microdebris that is
      difficult to distinguish from a solid mass.

PMID- 18096741
TI  - Fetal mediastinal lymphangiomas.
AB  - OBJECTIVE: The purpose of this series was to evaluate the prenatal sonographic
      findings and postnatal outcomes in 2 fetuses with mediastinal lymphangiomas.
      METHODS: The fetal images were compared with postnatal imaging and surgical
      findings. RESULTS: The 2 fetuses had anechoic mediastinal masses at 25 and 22
      weeks, which proved to be lymphangiomas. One, located in the anterior
      mediastinum, also enveloped the superior vena cava, brachial plexus, phrenic
      nerve, larynx, and lower parts of the neck vessels and extended into the
      subcutaneous tissues of the anterior chest wall through an intercostal space. In
      the second patient, the lymphangioma appeared to be a unilocular cyst, which
      involved the deep tissues of the neck as well as the posterior and lateral
      mediastinum. Both required 2 interventions after birth. CONCLUSIONS: Fetal
      mediastinal lymphangiomas appeared anechoic and sent extensions into the neck in
      the first case, around the superior vena cava, through the intercostal spaces to
      the skin, and around the brachial plexus in the second case, and deviated the
      trachea in both cases. In 1 case, there was also ectasia of the superior vena
      cava. This ability to entwine around vital structures can make it difficult to
      determine the extent of involvement on antenatal sonography and to remove
      lymphangiomas completely, and recurrence is common.

PMID- 18096742
TI  - Three-dimensional sonographic findings associated with ectrodactyly ectodermal
      dysplasia clefting syndrome.
AB  - Ectrodactyly-ectrodermal dysplasia-clefting (EEC) syndrome is a rare autosomal
      dominant genetic syndrome. This condition is characterized by varying degrees of
      ectrodactyly and syndactyly of the hands and feet, a cleft lip with or without a
      cleft palate, and ectodermal dysplasia. In addition, abnormalities of the
      genitourinary system occur frequently in association with this syndrome. The wide
      clinical variability of EEC syndrome has been well documented in the literature,
      and none of the 3 cardinal signs seem to be obligatory. We present a case of
      classic familial EEC syndrome diagnosed by prenatal sonography at 17 weeks'
      gestation. In addition to tetraectrodactyly and a unilateral cleft lip and
      palate, renal dysplasia was noted on serial sonographic evaluation. Three
      dimensional (3D) surface rendering was used to supplement traditional 2
      dimensional (2D) imaging to further evaluate the fetal phenotype.

PMID- 18096743
TI  - Three-dimensional sonographic findings of a cervical pregnancy.
AB  - A cervical pregnancy is an uncommon ectopic pregnancy that accounts for less than
      1% of such gestations. This condition is associated with an extremely high risk
      of massive hemorrhage and previously often required hysterectomy. The current
      diagnostic modality of this potentially life-threatening condition is
      transvaginal sonography, supported at times by magnetic resonance imaging. The
      definitive diagnostic imaging feature of a cervical pregnancy is the location of
      a gestational sac in the cervix in the presence of a closed internal uterine
      cervical os. We report the 3-dimensional transvaginal sonographic findings of a
      cervical pregnancy at 6 weeks' gestation.

PMID- 18096744
TI  - An unusual cause of hydrocele: malpositioned ventriculoperitoneal shunt in the
      scrotum.

PMID- 18096745
TI  - Generic eukaryotic core promoter prediction using structural features of DNA.
AB  - Despite many recent efforts, in silico identification of promoter regions is
      still in its infancy. However, the accurate identification and delineation of
      promoter regions is important for several reasons, such as improving genome
      annotation and devising experiments to study and understand transcriptional
      regulation. Current methods to identify the core region of promoters require
      large amounts of high-quality training data and often behave like black box
      models that output predictions that are difficult to interpret. Here, we present
      a novel approach for predicting promoters in whole-genome sequences by using
      large-scale structural properties of DNA. Our technique requires no training, is
      applicable to many eukaryotic genomes, and performs extremely well in comparison
      with the best available promoter prediction programs. Moreover, it is fast,
      simple in design, and has no size constraints, and the results are easily
      interpretable. We compared our approach with 14 current state-of-the-art
      implementations using human gene and transcription start site data and analyzed
      the ENCODE region in more detail. We also validated our method on 12 additional
      eukaryotic genomes, including vertebrates, invertebrates, plants, fungi, and
      protists.

PMID- 18096746
TI  - Genome-wide analysis reveals regulatory role of G4 DNA in gene transcription.
AB  - G-quadruplex or G4 DNA, a four-stranded DNA structure formed in G-rich sequences,
      has been hypothesized to be a structural motif involved in gene regulation. In
      this study, we examined the regulatory role of potential G4 DNA motifs (PG4Ms)
      located in the putative transcriptional regulatory region (TRR, -500 to +500) of
      genes across the human genome. We found that PG4Ms in the 500-bp region
      downstream of the annotated transcription start site (TSS; PG4M(D500)) are
      associated with gene expression. Generally, PG4M(D500)-positive genes are
      expressed at higher levels than PG4M(D500)-negative genes, and an increased
      number of PG4M(D500) provides a cumulative effect. This observation was validated
      by controlling for attributes, including gene family, function, and promoter
      similarity. We also observed an asymmetric pattern of PG4M(D500) distribution
      between strands, whereby the frequency of PG4M(D500) in the coding strand is
      generally higher than that in the template strand. Further analysis showed that
      the presence of PG4M(D500) and its strand asymmetry are associated with
      significant enrichment of RNAP II at the putative TRR. On the basis of these
      results, we propose a model of G4 DNA-mediated stimulation of transcription with
      the hypothesis that PG4M(D500) contributes to gene transcription by maintaining
      the DNA in an open conformation, while the asymmetric distribution of PG4M(D500)
      considerably reduces the probability of blocking the progression of the RNA
      polymerase complex on the template strand. Our findings provide a comprehensive
      view of the regulatory function of G4 DNA in gene transcription.

PMID- 18096747
TI  - Comparative genomics beyond sequence-based alignments: RNA structures in the
      ENCODE regions.
AB  - Recent computational scans for non-coding RNAs (ncRNAs) in multiple organisms
      have relied on existing multiple sequence alignments. However, as sequence
      similarity drops, a key signal of RNA structure--frequent compensating base
      changes--is increasingly likely to cause sequence-based alignment methods to
      misalign, or even refuse to align, homologous ncRNAs, consequently obscuring that
      structural signal. We have used CMfinder, a structure-oriented local alignment
      tool, to search the ENCODE regions of vertebrate multiple alignments. In
      agreement with other studies, we find a large number of potential RNA structures
      in the ENCODE regions. We report 6587 candidate regions with an estimated false
      positive rate of 50%. More intriguingly, many of these candidates may be better
      represented by alignments taking the RNA secondary structure into account than
      those based on primary sequence alone, often quite dramatically. For example,
      approximately one-quarter of our predicted motifs show revisions in >50% of their
      aligned positions. Furthermore, our results are strongly complementary to those
      discovered by sequence-alignment-based approaches--84% of our candidates are not
      covered by Washietl et al., increasing the number of ncRNA candidates in the
      ENCODE region by 32%. In a group of 11 ncRNA candidates that were tested by RT
      PCR, 10 were confirmed to be present as RNA transcripts in human tissue, and most
      show evidence of significant differential expression across tissues. Our results
      broadly suggest caution in any analysis relying on multiple sequence alignments
      in less well-conserved regions, clearly support growing appreciation for the
      biological significance of ncRNAs, and strongly support the argument for
      considering RNA structure directly in any searches for these elements.

PMID- 18096748
TI  - Genome-wide discovery and verification of novel structured RNAs in Plasmodium
      falciparum.
AB  - We undertook a genome-wide search for novel noncoding RNAs (ncRNA) in the malaria
      parasite Plasmodium falciparum. We used the RNAz program to predict structures in
      the noncoding regions of the P. falciparum 3D7 genome that were conserved with at
      least one of seven other Plasmodium spp. genome sequences. By using Northern blot
      analysis for 76 high-scoring predictions and microarray analysis for the majority
      of candidates, we have verified the expression of 33 novel ncRNA transcripts
      including four members of a ncRNA family in the asexual blood stage. These
      transcripts represent novel structured ncRNAs in P. falciparum and are not
      represented in any RNA databases. We provide supporting evidence for purifying
      selection acting on the experimentally verified ncRNAs by comparing the
      nucleotide substitutions in the predicted ncRNA candidate structures in P.
      falciparum with the closely related chimp malaria parasite P. reichenowi. The
      high confirmation rate within a single parasite life cycle stage suggests that
      many more of the predictions may be expressed in other stages of the organism's
      life cycle.

PMID- 18096749
TI  - Controlled exchange of chromosomal arms reveals principles driving telomere
      interactions in yeast.
AB  - The 32 telomeres in the budding yeast genome cluster in three to seven
      perinuclear foci. Although individual telomeres and telomeric foci are in
      constant motion, preferential juxtaposition of some telomeres has been scored. To
      examine the principles that guide such long-range interactions, we differentially
      tagged pairs of chromosome ends and developed an automated three-dimensional
      measuring tool that determines distances between two telomeres. In yeast, all
      chromosomal ends terminate in TG(1-3) and middle repetitive elements, yet
      subgroups of telomeres also share extensive homology in subtelomeric coding
      domains. We find that up to 21 kb of >90% sequence identity does not promote
      telomere pairing in interphase cells. To test whether unique sequence elements,
      arm length, or chromosome territories influence juxtaposition, we reciprocally
      swapped terminal domains or entire chromosomal arms from one chromosome to
      another. We find that the distal 10 kb of Tel6R promotes interaction with Tel6L,
      yet only when the two telomeres are present on the same chromosome. By
      manipulating the length and sequence composition of the right arm of chr 5, we
      confirm that contact between telomeres on opposite chromatid arms of equal length
      is favored. These results can be explained by the polarized Rabl arrangement of
      yeast centromeres and telomeres, which promote to telomere pairing by allowing
      contact between chromosome arms of equal length in anaphase.

PMID- 18096750
TI  - Alternative approach to a heavy weight problem.
AB  - Obesity is reaching epidemic proportions in developed countries and represents a
      significant risk factor for hypertension, heart disease, diabetes, and
      dyslipidemia. Splicing mutations constitute at least 14% of disease-causing
      mutations, thus implicating polymorphisms that affect splicing as likely
      candidates for disease susceptibility. A recent study suggested that genes
      associated with obesity were significantly enriched for rare nucleotide variants.
      Here, we examined these variants and revealed that they are located near splice
      junctions and tend to affect exonic splicing regulatory sequences. We also show
      that the majority of the exons that harbor these SNPs are constitutively spliced,
      yet they exhibit weak splice sites, typical to alternatively spliced exons, and
      are hence suboptimal for recognition by the splicing machinery and prone to
      become alternatively spliced. Using ex vivo assays, we tested a few
      representative variants and show that they indeed affect splicing by causing a
      shift from a constitutive to an alternative pattern, suggesting a possible link
      between extreme body mass index and abnormal splicing patterns.

PMID- 18096751
TI  - Training-specific changes in cardiac structure and function: a prospective and
      longitudinal assessment of competitive athletes.
AB  - This prospective, longitudinal study examined the effects of participation in
      team-based exercise training on cardiac structure and function. Competitive
      endurance athletes (EA, n = 40) and strength athletes (SA, n = 24) were studied
      with echocardiography at baseline and after 90 days of team training. Left
      ventricular (LV) mass increased by 11% in EA (116 +/- 18 vs. 130 +/- 19 g/m(2); P
      < 0.001) and by 12% in SA (115 +/- 14 vs. 132 +/- 11 g/m(2); P < 0.001; P value
      for the compared Delta = NS). EA experienced LV dilation (end-diastolic volume:
      66.6 +/- 10.0 vs. 74.7 +/- 9.8 ml/m(2), Delta = 8.0 +/- 4.2 ml/m(2); P < 0.001),
      enhanced diastolic function (lateral E': 10.9 +/- 0.8 vs. 12.4 +/- 0.9 cm/s, P <
      0.001), and biatrial enlargement, while SA experience LV hypertrophy (posterior
      wall: 4.5 +/- 0.5 vs. 5.2 +/- 0.5 mm/m(2), P < 0.001) and diminished diastolic
      function (E' basal lateral LV: 11.6 +/- 1.3 vs. 10.2 +/- 1.4 cm/s, P < 0.001).
      Further, EA experienced right ventricular (RV) dilation (end-diastolic area:
      1,460 +/- 220 vs. 1,650 +/- 200 mm/m(2), P < 0.001) coupled with enhanced
      systolic and diastolic function (E' basal RV: 10.3 +/- 1.5 vs. 11.4 +/- 1.7 cm/s,
      P < 0.001), while SA had no change in RV parameters. We conclude that
      participation in 90 days of competitive athletics produces significant training
      specific changes in cardiac structure and function. EA develop biventricular
      dilation with enhanced diastolic function, while SA develop isolated, concentric
      left ventricular hypertrophy with diminished diastolic relaxation.

PMID- 18096752
TI  - Exercise-induced respiratory muscle fatigue: implications for performance.
AB  - It is commonly held that the respiratory system has ample capacity relative to
      the demand for maximal O(2) and CO(2) transport in healthy humans exercising near
      sea level. However, this situation may not apply during heavy-intensity,
      sustained exercise where exercise may encroach on the capacity of the respiratory
      system. Nerve stimulation techniques have provided objective evidence that the
      diaphragm and abdominal muscles are susceptible to fatigue with heavy, sustained
      exercise. The fatigue appears to be due to elevated levels of respiratory muscle
      work combined with an increased competition for blood flow with limb locomotor
      muscles. When respiratory muscles are prefatigued using voluntary respiratory
      maneuvers, time to exhaustion during subsequent exercise is decreased. Partially
      unloading the respiratory muscles during heavy exercise using low-density gas
      mixtures or mechanical ventilation can prevent exercise-induced diaphragm fatigue
      and increase exercise time to exhaustion. Collectively, these findings suggest
      that respiratory muscle fatigue may be involved in limiting exercise tolerance or
      that other factors, including alterations in the sensation of dyspnea or
      mechanical load, may be important. The major consequence of respiratory muscle
      fatigue is an increased sympathetic vasoconstrictor outflow to working skeletal
      muscle through a respiratory muscle metaboreflex, thereby reducing limb blood
      flow and increasing the severity of exercise-induced locomotor muscle fatigue. An
      increase in limb locomotor muscle fatigue may play a pivotal role in determining
      exercise tolerance through a direct effect on muscle force output and a feedback
      effect on effort perception, causing reduced motor output to the working limb
      muscles.

PMID- 18096753
TI  - Noninvasive determination of exercise-induced hydrodgen ion threshold through
      direct optical measurement.
AB  - The intensity of exercise above which oxygen uptake (Vo2) does not account for
      all of the required energy to perform work has been associated with lactate
      accumulation in the blood (lactate threshold, LT) and elevated carbon dioxide
      output (gas exchange threshold). An increase in hydrogen ion concentration ([H+])
      is approximately concurrent with elevation of blood lactate and CO2 output during
      exercise. Near-infrared spectra (NIRS) and invasive interstitial fluid pH (pHm)
      were measured in the flexor digitorum profundus during handgrip exercise to
      produce a mathematical model relating the two measures with an estimated error of
      0.035 pH units. This NIRS pHm model was subsequently applied to spectra collected
      from the vastus lateralis of 10 subjects performing an incremental-intensity
      cycle protocol. Muscle oxygen saturation (SmO2) was also calculated from spectra.
      We hypothesized that a H+ threshold could be identified for these subjects and
      that it would be different from but correlated with the LT. Lactate, gas
      exchange, SmO2, and H+ thresholds were determined as a function of Vo2 using
      bilinear regression. LT was significantly different from both the gas exchange
      threshold (Delta = 0.27 +/- 0.29 l/min) and H+ threshold (Delta = 0.29 +/- 0.23
      l/min), but the gas exchange threshold was not significantly different from the
      H+ threshold (Delta = 0.00 +/- 0.38 l/min). The H+ threshold was strongly
      correlated with LT (R2 = 0.95) and the gas exchange threshold (R2 = 0.85). This
      initial study demonstrates the feasibility of noninvasive pHm estimations, the
      determination of H+ threshold, and the relationship between H+ and classical
      metabolic thresholds during incremental exercise.

PMID- 18096754
TI  - Gastrocnemius muscle specific force in boys and men.
AB  - The aim of this study was to assess whether the in vivo specific force and
      architectural characteristics of the lateral gastrocnemius (GL) muscle of early
      pubescent boys (n = 11, age = 10.9 +/- 0.3 yr, Tanner stage 2) differed from
      those of adult men (n = 12, age = 25.3 +/- 4.4 yr). Plantarflexor torque was 55%
      lower in the boys (77.4 +/- 21.4 N x m) compared with the adults (175.6 +/- 31.7
      N x m, P < 0.01). Physiological cross-sectional area (PCSA), determined in vivo
      using ultrasonography and MRI, was 52% smaller in the boys (P < 0.01). No
      difference was found in pennation angle, or in the ratio of fascicle length
      (L(f)) to muscle length between the boys and men. Moment arm length was 25%
      smaller in the boys (P < 0.01). Antagonist coactivation, assessed using surface
      EMG on the dorsiflexors, was not different between the boys and men (11.8 +/-
      6.7% and 13.5 +/- 5.8%, respectively). Surprisingly, GL force normalized to PCSA
      (specific force) was significantly higher (21%) in the boys than in the men (13.1
      +/- 2.0 vs. 15.9 +/- 2.7 N/cm(2), P < 0.05). This finding could not be explained
      by differences in moment arm length, muscle activation, or architecture, and
      other factors, such as tendinous characteristics and/or changes in moment arm
      length with contraction, may be held responsible. These observations warrant
      further investigation.

PMID- 18096755
TI  - Sustained hypoxia-induced proliferation of carotid body type I cells in rats.
AB  - Sustained hypoxia (SH) has been shown to cause profound morphological and
      cellular changes in carotid body (CB). However, results regarding whether SH
      causes CB type I cell proliferation are conflicting. By using bromodeoxyuridine,
      a uridine analog that is stably incorporated into cells undergoing DNA synthesis,
      we have found that SH causes the type I cell proliferation in the CB; the
      proliferation occurs mainly during the first 1-3 days of hypoxic exposure.
      Moreover, the new cells survive for at least 1 mo after the return to normoxia.
      Also, SH does not cause any cell death in CB as examined by the terminal
      deoxynucleotidyl transferase-mediated dUTP-X nick-end labeling assay. Taken
      together, our results suggest that SH stimulates CB type I cell proliferation,
      which may produce long-lasting changes in CB morphology and function.

PMID- 18096756
TI  - Chronic inflation of ferret lungs with CPAP reduces airway smooth muscle
      contractility in vivo and in vitro.
AB  - The mechanical stress imposed on the lungs during breathing is an important
      modulator of airway responsiveness in vivo. Our recent study demonstrated that
      continuous positive airway pressure applied to the lungs of nonanesthetized,
      tracheotomized rabbits for 4 days decreased lower respiratory system
      responsiveness to challenge with ACh (Xue Z, Zhang L, Ramchandani R, Liu Y,
      Antony VB, Gunst SJ, Tepper RS. J. Appl Physiol 99: 677-682, 2005). In addition,
      airway segments excised from the lungs of these animals and studied in vitro
      exhibited reduced contractility. However, the mechanism for this reduction in
      contractility was not determined. The stress-induced decrease in airway
      responsiveness could have resulted from alterations in the excitation-contraction
      coupling mechanisms of the smooth muscle cells, or it might reflect changes in
      the structure and/or composition of the airway wall tissues. In the present
      study, we assessed the effect of prolonged chronic stress of the lungs in vivo on
      airway smooth muscle force generation, myosin light chain phosphorylation, and
      airway wall structure. To enhance the potential development of stress-induced
      structural changes, we applied mechanical stress for a prolonged period of time
      of 2-3 wk. Our results demonstrate a direct connection between the decreased
      airway responsiveness caused by chronic mechanical stress of the lungs in vivo
      and a persistent decrease in contractile protein activation in the airway smooth
      muscle isolated from those lungs. The chronic stress also caused an increase in
      airway size but no detectable changes in the composition of the airway wall.

PMID- 18096757
TI  - Estrogen influences satellite cell activation and proliferation following
      downhill running in rats.
AB  - To investigate the influence of estrogen on postexercise muscle repair processes,
      we examined the effects of estrogen supplementation (0.25-mg pellet) on numbers
      of myofibers positive for markers of total, activated, and proliferating
      satellite cells in rat skeletal muscles 72 h following downhill running.
      Ovariectomized female rats (n = 44) were divided into four groups (n = 11 per
      group): sham (no estrogen) controls (SC); sham, exercised (SE); estrogen
      supplemented controls (EC); and estrogen-supplemented, exercised (EE). After 8
      days of estrogen exposure, animals were exposed to 90 min of treadmill running at
      17 m/min (-13.5 degrees ). Seventy-two hours later, soleus and white vastus
      muscles were removed and immunostained for total [paired box homeotic gene 7
      (Pax7)], [activated myogenic differentiation factor D (MyoD)], and proliferating
      [5-bromo-2'-deoxyuridine (BrdU)] satellite cells. beta-Glucuronidase activity was
      increased (P < 0.05) in both muscles following exercise; however, the
      postexercise elevations in enzyme activity were attenuated in the EE group
      compared with the SE group in the soleus (P < 0.05). Immunohistochemical analysis
      revealed that exercised groups displayed increased numbers of myofibers
      containing total, activated, and proliferating satellite cells compared with
      control groups (P < 0.05). Furthermore, greater numbers of fibers positive for
      markers of total, activated, and proliferating satellite cells were observed
      postexercise in EE animals compared with SE animals for both muscles (P < 0.05).
      The results demonstrate that estrogen may potentially influence post-damage
      repair of skeletal muscle through activation of satellite cells.

PMID- 18096758
TI  - Age-dependent kinetics and metabolism of dichloroacetate: possible relevance to
      toxicity.
AB  - Dichloroacetate (DCA) is an investigational drug for certain metabolic diseases.
      It is biotransformed principally by the zeta-1 family isoform of glutathione
      transferase (GSTz1), also known as maleylacetoacetate isomerase (MAAI), which
      catalyzes the penultimate step in tyrosine catabolism. DCA causes a reversible
      peripheral neuropathy in several species, including humans. However, recent
      clinical trials indicate that adults are considerably more susceptible to this
      adverse effect than children. We evaluated the kinetics and biotransformation of
      DCA and its effects on tyrosine metabolism in nine patients treated for 6 months
      with 25 mg/kg/day and in rats treated for 5 days with 50 mg/kg/day. We also
      measured the activity and expression of hepatic GSTz1/MAAI. Chronic
      administration of DCA causes a striking age-dependent decrease in its plasma
      clearance and an increase in its plasma half-life in patients and rats. Urinary
      excretion of unchanged DCA in rats increases with age, whereas oxalate, an end
      product of DCA metabolism, shows the opposite trend. Low concentrations of
      monochloroacetate (MCA), which is known to be neurotoxic, increase as a function
      of age in the urine of dosed rats. MCA was detectable in plasma only of older
      animals. Hepatic GSTz1/MAAI-specific activity was inhibited equally by DCA
      treatment among all age groups, whereas plasma and urinary levels of
      maleylacetone, a natural substrate for this enzyme, increased with age. We
      conclude that age is an important variable in the in vivo metabolism and
      elimination of DCA and that it may account, in part, for the neurotoxicity of
      this compound in humans and other species.

PMID- 18096759
TI  - S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4
      c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a preferential dopamine D3 versus D2
      receptor antagonist and potential antipsychotic agent: III. Actions in models of
      therapeutic activity and induction of side effects.
AB  - In contrast to clinically available antipsychotics, the novel
      benzopyranopyrrolidine derivative, S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b
      tetrahydro[1]benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), behaves
      as a preferential antagonist of D(3) versus D(2) receptors and does not interact
      with histamine H(1) and muscarinic receptors. In contrast to haloperidol,
      clozapine, olanzapine, and risperidone, S33138 (0.16-2.5 mg/kg s.c.) did not
      disrupt performance in passive-avoidance and five-choice serial reaction time
      procedures. Furthermore, upon either systemic administration (0.04-2.5 mg/kg
      s.c.) or introduction into the frontal cortex (0.04-0.63 mug/side), S33138
      potently attenuated the perturbation of social recognition by scopolamine or a
      prolonged intersession delay. Over a comparable and low-dose range, S33138 (0.04
      0.63 mg/kg s.c.) elevated dialysis levels of acetylcholine in the frontal cortex
      of freely moving rats. At higher doses (2.5-10.0 mg/kg s.c.), S33138 also
      increased frontocortical levels of histamine, whereas monoamines, glutamate,
      glycine, and GABA were unaffected. By analogy to the other antipsychotics, S33138
      (0.63-10.0 mg/kg s.c.) inhibited conditioned avoidance responses in rats,
      apomorphine-induced climbing in mice, and hyperlocomotion elicited by
      amphetamine, cocaine, dizocilpine, ketamine, and phencyclidine in rats. S33138
      (0.16-2.5 mg/kg s.c.) also blocked the reduction of prepulse inhibition elicited
      by apomorphine. In comparison with the above actions, only "high" doses of S33138
      (10.0-40.0 mg/kg s.c.) elicited catalepsy. To summarize, reflecting preferential
      blockade of D(3) versus D(2) receptors, S33138 preserves and/or enhances
      cognitive function, increases frontocortical cholinergic transmission, and is
      active in models of antipsychotic properties at doses well below those inducing
      catalepsy. In comparison with clinically available agents, S33138 displays, thus,
      a distinctive and promising profile of potential antipsychotic properties.

PMID- 18096760
TI  - Characterization of the molecular fragment that is responsible for agonism of
      pergolide at serotonin 5-Hydroxytryptamine2B and 5-Hydroxytryptamine2A receptors.
AB  - Cardiac-valve regurgitation observed in Parkinson patients treated with the
      ergoline dopamine receptor agonist 8beta-methylthiomethyl-6-propylergoline
      (pergolide) has been associated with the agonist efficacy of the drug at 5
      hydroxytryptamine(2B) (5-HT(2B)) receptors. 5-HT(2A) receptors may also play a
      role in pergolide-induced cardiac-valve regurgitation. We studied the
      pharmacological profile of pergolide and eight derivatives in porcine vascular
      rings endowed with 5-HT(2B) and 5-HT(2A) receptors to detect the molecular
      fragment of the pergolide molecule that may be responsible for agonism at these
      receptors. Pergolide derivatives showed a different substitution pattern at N(6),
      and the side chain at C(8) was modified by replacement of the sulfur against an
      oxygen atom. We demonstrate that the potent agonism of pergolide both at 5-HT(2B)
      and 5-HT(2A) receptors is retained when the N(6) propyl substituent is replaced
      by ethyl. However, agonism can be converted into antagonism if N(6) propyl is
      replaced by methyl. The N(6)-unsubstituted derivative was a low efficacy 5-HT(2B)
      receptor partial agonist and a 5-HT(2A) receptor antagonist. This pharmacological
      pattern was also applicable for pergolide congeners with an oxygen in the side
      chain at C(8). 6-Methylpergolide retained agonist efficacy and potency compared
      with pergolide at human (h) D(2LONG(L)) and hD(2SHORT(S)) receptors as determined
      by guanosine 5'-O-(3-[(35)S]thio)triphosphate binding. Based on the ability of
      pergolide to produce potent agonism at 5-HT(2B) receptors and the failure of 6
      methylpergolide to act as an agonist but as a potent antagonist, we conclude that
      the N(6) propyl substituent of pergolide is crucial for 5-HT(2B) receptor agonism
      and thus a determinant of valvular regurgitation.

PMID- 18096762
TI  - Ongoing improvement in long-term survival of patients with Hodgkin disease at all
      ages and recent catch-up of older patients.
AB  - Since the breakthroughs in combination chemotherapy of patients with Hodgkin
      disease (HD) starting in the 1960s, prognosis of patients has been rising
      steadily. Trends in long-term survival of patients with HD on the population
      level should therefore be monitored in an as timely as possible manner. We
      assessed trends in age specific 5- and 10-year relative survival of patients with
      HD in the United States from 1980-1984 to 2000-2004 from the 1973-2004 database
      of the Surveillance, Epidemiology, and End Results (SEER) Program. Period
      analysis was used to disclose recent developments with minimum delay. Overall, 5
      year relative survival steadily increased from 73.5% to 85.2% (+11.7 percentage
      units), and 10-year relative survival increased from 62.1% to 80.1% (+18.0
      percentage units) between 1980-1984 and 2000-2004, according to period analysis.
      The increase was particularly pronounced for patients aged 45 to 59 years and 60
      years and older (increases in 10-year relative survival by 24.8 and 23.3
      percentage points, respectively). Nevertheless, a strong age gradient persisted,
      with 10-year relative survival of 92.7%, 88.7%, 84.9%, 76.2%, and 44.9% in
      patients aged 15 to 24 years, 25 to 34 years, 35 to 44 years, 45 to 54 years, and
      60 years and older, respectively, in 2000-2004. Our period analysis discloses
      ongoing, major improvement in long-term survival of patients with HD in recent
      years, particularly among older patients.

PMID- 18096761
TI  - Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and
      congestive heart failure.
AB  - Pharmacologic activation of the heterodimeric HIF transcription factor appears
      promising as a strategy to treat diseases, such as anemia, myocardial infarction,
      and stroke, in which tissue hypoxia is a prominent feature. HIF accumulation is
      normally linked to oxygen availability because an oxygen-dependent
      posttranslational modification (prolyl hydroxylation) marks the HIFalpha subunit
      for polyubiquitination and destruction. Three enzymes (PHD1, PHD2, and PHD3)
      capable of catalyzing this reaction have been identified, although PHD2 (also
      called Egln1) appears to be the primary HIF prolyl hydroxylase in cell culture
      experiments. We found that conditional inactivation of PHD2 in mice is sufficient
      to activate a subset of HIF target genes, including erythropoietin, leading to
      striking increases in red blood cell production. Mice lacking PHD2 exhibit
      premature mortality associated with marked venous congestion and dilated
      cardiomyopathy. The latter is likely the result of hyperviscosity syndrome and
      volume overload, although a direct effect of chronic, high-level HIF stimulation
      on cardiac myocytes cannot be excluded.

PMID- 18096765
TI  - Cytotoxic T lymphocytes overcome Bcl-2 inhibition: target cells contribute to
      their own demise.
AB  - Cytotoxic T lymphocytes (CTLs) eliminate pathogenic cells in large part through
      the activity of the serine protease granzyme B (grB). However, while the
      apoptotic activity of grB is blocked by over-expression of Bcl-2, CTLs can still
      kill target cells through an ill-defined Bcl-2-independent pathway. In this
      report, we have identified key modulators of this Bcl-2-independent cell-death
      pathway, which is induced by CTLs and not purified components. Surprisingly,
      activation of this pathway is reliant on grB. Furthermore, this novel pathway
      requires mitochondrial contribution through triggering of permeability transition
      and generation of reactive oxygen species, yet is functional in the absence of
      Bax/Bak. This pathway stimulates movement of target cell mitochondria toward the
      point of contact with the CTLs and importantly, inhibition of this directed
      movement attenuates killing. Therefore, we propose that CTLs initiate a target
      cell response that activates multiple mitochondrial pathways. This ensures that
      CTLs can eliminate those target cells that have compromised apoptotic potential
      due to overexpression of Bcl-2.

PMID- 18096763
TI  - Killer artificial antigen-presenting cells: a novel strategy to delete specific T
      cells.
AB  - Several cell-based immunotherapy strategies have been developed to specifically
      modulate T cell-mediated immune responses. These methods frequently rely on the
      utilization of tolerogenic cell-based antigen-presenting cells (APCs). However,
      APCs are highly sensitive to cytotoxic T-cell responses, thus limiting their
      therapeutic capacity. Here, we describe a novel bead-based approach to modulate T
      cell responses in an antigen-specific fashion. We have generated killer
      artificial APCs (kappaaAPCs) by coupling an apoptosis-inducing alpha-Fas (CD95)
      IgM mAb together with HLA-A2 Ig molecules onto beads. These kappaaAPCs deplete
      targeted antigen-specific T cells in a Fas/Fas ligand (FasL)-dependent fashion. T
      cell depletion in cocultures is rapidly initiated (30 minutes), dependent on the
      amount of kappaaAPCs and independent of activation-induced cell death (AICD).
      kappaaAPCs represent a novel technology that can control T cell-mediated immune
      responses, and therefore has potential for use in treatment of autoimmune
      diseases and allograft rejection.

PMID- 18096764
TI  - DNA variants in the dihydrofolate reductase gene and outcome in childhood ALL.
AB  - Dihydrofolate reductase (DHFR) is the major target of methotrexate (MTX), a key
      component in childhood acute lymphoblastic leukemia (ALL) treatment. A total of
      15 polymorphisms in DHFR promoter were analyzed, and 3 sites (C-1610G/T, C-680A,
      and A-317G) were identified as sufficient to define observed haplotypes (tag
      single nucleotide polymorphisms [tagSNPs]). These polymorphisms were investigated
      for association with treatment response in 277 children with ALL. Lower event
      free survival (EFS) was associated with homozygosity for the allele A-317 and C
      1610 (P=.03 and .02), and with the haplotype *1, defined by both C-1610 and A-317
      alleles (P=.03). The haplotype *1 conferred higher transcriptional activity
      (P<.01 compared with haplotypes generating minimal luciferase expression).
      Quantitative mRNA analysis showed higher DHFR levels for particular haplotype *1
      carriers (P<.01). The analysis combining haplotype *1 with thymidylate synthase
      (TS) and cyclin D1 (CCND1) genotypes previously shown to affect ALL outcome
      showed that the number of event-predisposing genotypes was associated with
      increasingly lower EFS (P<.001). In conclusion, DHFR promoter polymorphisms are
      associated with worse ALL outcome, likely due to a higher DHFR expression.
      Combined effects among genes of the folate cycle can further accentuate
      differences in the response to the treatment.

PMID- 18096766
TI  - Galactosylation does not prevent the rapid clearance of long-term, 4 degrees C
      stored platelets.
AB  - Cold storage of platelets for transfusion is desirable to extend platelet storage
      times and to prevent bacterial growth. However, the rapid clearance of cold
      stored platelets prevents their use. A novel method for preventing the rapid
      clearance of cold-stored platelets has previously been developed in a murine
      model. Cold storage induces the clustering and recognition of exposed beta-N
      acetylglucosamine (betaGlcNAc) on platelet surfaces. Glycosylation of betaGlcNAc
      residues with uridine 5'-diphosphogalactose (UDP-galactose) results in the normal
      survival of short-term (2 h) 0 degrees C-stored murine platelets. Based on this
      finding, we developed a similar glycosylation process by adding UDP-galactose to
      human apheresis platelets. A phase 1 clinical trial was conducted transfusing
      radiolabeled autologous apheresis platelets stored for 48 hours at 4 degrees C
      with or without pretreatment with UDP-galactose. In contrast to the murine study,
      galactosylation of human platelets did not prevent the accelerated platelet
      clearance routinely observed after 4 degrees C storage. We next developed a
      murine model of platelet storage for 48 hours at 4 degrees C and showed that UDP
      galactose treatment of murine platelets also did not prevent their rapid
      clearance, in agreement with the human platelet study. We conclude that different
      mechanisms of clearance may exist for short- and long-term cold-stored platelets.

PMID- 18096767
TI  - Time-resolved observation and control of superexchange interactions with
      ultracold atoms in optical lattices.
AB  - Quantum mechanical superexchange interactions form the basis of quantum magnetism
      in strongly correlated electronic media. We report on the direct measurement of
      superexchange interactions with ultracold atoms in optical lattices. After
      preparing a spin-mixture of ultracold atoms in an antiferromagnetically ordered
      state, we measured coherent superexchange-mediated spin dynamics with coupling
      energies from 5 hertz up to 1 kilohertz. By dynamically modifying the potential
      bias between neighboring lattice sites, the magnitude and sign of the
      superexchange interaction can be controlled, thus allowing the system to be
      switched between antiferromagnetic and ferromagnetic spin interactions. We
      compare our findings to predictions of a two-site Bose-Hubbard model and find
      very good agreement, but are also able to identify corrections that can be
      explained by the inclusion of direct nearest-neighbor interactions.

PMID- 18096768
TI  - GaN photonic-crystal surface-emitting laser at blue-violet wavelengths.
AB  - Shorter-wavelength surface-emitting laser sources are important for a variety of
      fields, including photonics, information processing, and biology. We report on
      the creation of a current-driven blue-violet photonic-crystal surface-emitting
      laser. We have developed a fabrication method, named "air holes retained over
      growth," in order to construct a two-dimensional gallium nitride (GaN)/air
      photonic-crystal structure. The resulting periodic structure has a photonic
      crystal band-edge effect sufficient for the successful operation of a current
      injection surface-emitting laser. This represents an important step in the
      development of laser sources that could be focused to a size much less than the
      wavelength and be integrated two-dimensionally at such short wavelengths.

PMID- 18096770
TI  - Breakthrough of the year. Human genetic variation.
AB  - Equipped with faster, cheaper technologies for sequencing DNA and assessing
      variation in genomes on scales ranging from one to millions of bases, researchers
      are finding out how truly different we are from one another.

PMID- 18096769
TI  - Breakthrough of the year.

PMID- 18096771
TI  - Breakthrough of the year. It's all about me.
AB  - Along with the flood of discoveries in human genetics, 2007 saw the birth of a
      new industry: personal genomics. But researchers worry that these services open
      up a Pandora's box of ethical issues.

PMID- 18096772
TI  - Breakthrough of the year. The runners-up.
AB  - The runners-up for 2007's Breakthrough of the Year include advances in cellular
      and structural biology, astrophysics, physics, immunology, synthetic chemistry,
      neuroscience, and computer science.

PMID- 18096773
TI  - Breakthrough of the year. How'd we do?

PMID- 18096774
TI  - Breakthrough of the year. Global warming, hotter than ever.
AB  - Climate change, a perennial runner-up for Breakthrough of the Year, broke from
      the pack this year--both in the pages of this section and in the public arena.

PMID- 18096775
TI  - Breakthrough of the year. Areas to watch.

PMID- 18096776
TI  - Climate change. Grassroots effort pays dividends on presidential campaign trail.

PMID- 18096777
TI  - Research funding. U.K. cutbacks rattle physics, astronomy.

PMID- 18096778
TI  - AIDS research. Trials of NIH's AIDS vaccine get a yellow light.

PMID- 18096779
TI  - Scientific publishing. Bruce Alberts named Science Editor-in-Chief.

PMID- 18096780
TI  - Microbiology. Detoxifying enzyme helps animals stomach bacteria.

PMID- 18096781
TI  - Evolution. Did an asteroid shower kick-start the great diversification?

PMID- 18096782
TI  - Universities. Questions swirl around Kessler's abrupt dismissal from UCSF.

PMID- 18096784
TI  - Climate change. Global warming coming home to roost in the American West.

PMID- 18096783
TI  - Science and the public. Animal extremists get personal.

PMID- 18096785
TI  - Infectious diseases. Chikungunya: no longer a third world disease.

PMID- 18096786
TI  - David King interview. U.K. science adviser offers some parting shots.

PMID- 18096787
TI  - Cancer filter deja vu.

PMID- 18096788
TI  - One woman's balancing act.

PMID- 18096789
TI  - Stem cell breakthrough: don't forget ethics.

PMID- 18096790
TI  - CO2 emissions: getting bang for the buck.

PMID- 18096791
TI  - Mentoring. Linking student interests to science curricula.

PMID- 18096792
TI  - Ethics. The ethics of international research with abandoned children.

PMID- 18096793
TI  - History of science. Hoyle's equation.

PMID- 18096795
TI  - Atmospheric science. Revisiting ozone depletion.

PMID- 18096794
TI  - Molecular biology. The two faces of miRNA.

PMID- 18096796
TI  - Development. Is therapeutic cloning dead?

PMID- 18096797
TI  - Materials science. The flow of glass.

PMID- 18096798
TI  - Sexual selection in males and females.
AB  - Research on sexual selection shows that the evolution of secondary sexual
      characters in males and the distribution of sex differences are more complex than
      was initially suggested but does not undermine our understanding of the
      evolutionary mechanisms involved. However, the operation of sexual selection in
      females has still received relatively little attention. Recent studies show that
      both intrasexual competition between females and male choice of mating partners
      are common, leading to strong sexual selection in females and, in extreme cases,
      to reversals in the usual pattern of sex differences in behavior and morphology.

PMID- 18096799
TI  - Combinatorial synthesis of peptide arrays onto a microchip.
AB  - Arrays promise to advance biology through parallel screening for binding
      partners. We show the combinatorial in situ synthesis of 40,000 peptide spots per
      square centimeter on a microchip. Our variant Merrifield synthesis immobilizes
      activated amino acids as monomers within particles, which are successively
      attracted by electric fields generated on each pixel electrode of the chip. With
      all different amino acids addressed, particles are melted at once to initiate
      coupling. Repetitive coupling cycles should allow for the translation of whole
      proteomes into arrays of overlapping peptides that could be used for proteome
      research and antibody profiling.

PMID- 18096800
TI  - Structural rearrangements that govern flow in colloidal glasses.
AB  - Structural rearrangements are an essential property of atomic and molecular
      glasses; they are critical in controlling resistance to flow and are central to
      the evolution of many properties of glasses, such as their heat capacity and
      dielectric constant. Despite their importance, these rearrangements cannot
      directly be visualized in atomic glasses. We used a colloidal glass to obtain
      direct three-dimensional images of thermally induced structural rearrangements in
      the presence of an applied shear. We identified localized irreversible shear
      transformation zones and determined their formation energy and topology. A
      transformation favored successive ones in its vicinity. Using continuum models,
      we elucidated the interplay between applied strain and thermal fluctuations that
      governs the formation of these zones in both colloidal and molecular glasses.

PMID- 18096801
TI  - Role of intermolecular forces in defining material properties of protein
      nanofibrils.
AB  - Protein molecules have the ability to form a rich variety of natural and
      artificial structures and materials. We show that amyloid fibrils, ordered
      supramolecular nanostructures that are self-assembled from a wide range of
      polypeptide molecules, have rigidities varying over four orders of magnitude, and
      constitute a class of high-performance biomaterials. We elucidate the molecular
      origin of fibril material properties and show that the major contribution to
      their rigidity stems from a generic interbackbone hydrogen-bonding network that
      is modulated by variable side-chain interactions.

PMID- 18096802
TI  - A sulfur dioxide climate feedback on early Mars.
AB  - Ancient Mars had liquid water on its surface and a CO2-rich atmosphere. Despite
      the implication that massive carbonate deposits should have formed, these have
      not been detected. On the basis of fundamental chemical and physical principles,
      we propose that climatic conditions enabling the existence of liquid water were
      maintained by appreciable atmospheric concentrations of volcanically degassed SO2
      and H2S. The geochemistry resulting from equilibration of this atmosphere with
      the hydrological cycle is shown to inhibit the formation of carbonates. We
      propose an early martian climate feedback involving SO2, much like that
      maintained by CO2 on Earth.

PMID- 18096803
TI  - Coupled 142Nd-143Nd isotopic evidence for Hadean mantle dynamics.
AB  - The oldest rocks-3.85 billion years old-from southwest Greenland have coupled
      neodymium-142 excesses (from decay of now-extinct samarium-146; half-life, 103
      million years) and neodymium-143 excesses (from decay of samarium-147; half-life,
      106 billion years), relative to chondritic meteorites, that directly date the
      formation of chemically distinct silicate reservoirs in the first 30 million to
      75 million years of Earth history. The differences in 142Nd signatures of coeval
      rocks from the two most extensive crustal relicts more than 3.6 billion years
      old, in Western Australia and southwest Greenland, reveal early-formed large
      scale chemical heterogeneities in Earth's mantle that persisted for at least the
      first billion years of Earth history. Temporal variations in 142Nd signatures
      track the subsequent incomplete remixing of very-early-formed mantle chemical
      domains.

PMID- 18096804
TI  - High-pressure creep of serpentine, interseismic deformation, and initiation of
      subduction.
AB  - The supposed low viscosity of serpentine may strongly influence subduction-zone
      dynamics at all time scales, but until now its role could not be quantified
      because measurements relevant to intermediate-depth settings were lacking.
      Deformation experiments on the serpentine antigorite at high pressures and
      temperatures (1 to 4 gigapascals, 200 degrees to 500 degrees C) showed that the
      viscosity of serpentine is much lower than that of the major mantle-forming
      minerals. Regardless of the temperature, low-viscosity serpentinized mantle at
      the slab surface can localize deformation, impede stress buildup, and limit the
      downdip propagation of large earthquakes at subduction zones. Antigorite enables
      viscous relaxation with characteristic times comparable to those of long-term
      postseismic deformations after large earthquakes and slow earthquakes. Antigorite
      viscosity is sufficiently low to make serpentinized faults in the oceanic
      lithosphere a site for subduction initiation.

PMID- 18096805
TI  - A comprehensive phylogeny of beetles reveals the evolutionary origins of a
      superradiation.
AB  - Beetles represent almost one-fourth of all described species, and knowledge about
      their relationships and evolution adds to our understanding of biodiversity. We
      performed a comprehensive phylogenetic analysis of Coleoptera inferred from three
      genes and nearly 1900 species, representing more than 80% of the world's
      recognized beetle families. We defined basal relationships in the Polyphaga
      supergroup, which contains over 300,000 species, and established five families as
      the earliest branching lineages. By dating the phylogeny, we found that the
      success of beetles is explained neither by exceptional net diversification rates
      nor by a predominant role of herbivory and the Cretaceous rise of angiosperms.
      Instead, the pre-Cretaceous origin of more than 100 present-day lineages suggests
      that beetle species richness is due to high survival of lineages and sustained
      diversification in a variety of niches.

PMID- 18096806
TI  - Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation
      of RhoA by GPCRs.
AB  - The guanine nucleotide exchange factor p63RhoGEF is an effector of the
      heterotrimeric guanine nucleotide-binding protein (G protein) Galphaq and thereby
      links Galphaq-coupled receptors (GPCRs) to the activation of the small-molecular
      weight G protein RhoA. We determined the crystal structure of the Galphaq
      p63RhoGEF-RhoA complex, detailing the interactions of Galphaq with the Dbl and
      pleckstrin homology (DH and PH) domains of p63RhoGEF. These interactions involve
      the effector-binding site and the C-terminal region of Galphaq and appear to
      relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet,
      and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear
      to activate RhoA both in vitro and in intact cells. We propose that this
      structure represents the crux of an ancient signal transduction pathway that is
      expected to be important in an array of physiological processes.

PMID- 18096807
TI  - Regulation of replication fork progression through histone supply and demand.
AB  - DNA replication in eukaryotes requires nucleosome disruption ahead of the
      replication fork and reassembly behind. An unresolved issue concerns how histone
      dynamics are coordinated with fork progression to maintain chromosomal stability.
      Here, we characterize a complex in which the human histone chaperone Asf1 and
      MCM2-7, the putative replicative helicase, are connected through a histone H3-H4
      bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at
      replication sites, and similar defects arise from overproduction of new histone
      H3-H4 that compromises Asf1 function. These data link Asf1 chaperone function,
      histone supply, and replicative unwinding of DNA in chromatin. We propose that
      Asf1, as a histone acceptor and donor, handles parental and new histones at the
      replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a
      means to fine-tune replication fork progression and histone supply and demand.

PMID- 18096808
TI  - Rapid changes in throughput from single motor cortex neurons to muscle activity.
AB  - Motor cortex output is capable of considerable reorganization, which involves
      modulation of excitability within the cortex. Does such reorganization also
      involve changes beyond the cortex, at the level of throughput from single motor
      cortex neurons to muscle activity? We examined such throughput during a paradigm
      that provided incentive for enhancing functional connectivity from motor cortex
      neurons to muscles. Short-latency throughput from a recorded neuron to muscle
      activity not present during some behavioral epochs often appeared during others.
      Such changes in throughput could not always be attributed to a higher neuron
      firing rate, to more ongoing muscle activity, or to neuronal synchronization,
      indicating that reorganization of motor cortex output may involve rapid changes
      in functional connectivity from single motor cortex neurons to alpha-motoneuron
      pools.

PMID- 18096809
TI  - Cognitive recovery in socially deprived young children: the Bucharest Early
      Intervention Project.
AB  - In a randomized controlled trial, we compared abandoned children reared in
      institutions to abandoned children placed in institutions but then moved to
      foster care. Young children living in institutions were randomly assigned to
      continued institutional care or to placement in foster care, and their cognitive
      development was tracked through 54 months of age. The cognitive outcome of
      children who remained in the institution was markedly below that of never
      institutionalized children and children taken out of the institution and placed
      into foster care. The improved cognitive outcomes we observed at 42 and 54 months
      were most marked for the youngest children placed in foster care. These results
      point to the negative sequelae of early institutionalization, suggest a possible
      sensitive period in cognitive development, and underscore the advantages of
      family placements for young abandoned children.

PMID- 18096810
TI  - Spanish diabetes self-management with and without automated telephone
      reinforcement: two randomized trials.
AB  - OBJECTIVE: To determine 1) whether participants in the Spanish Diabetes Self
      Management Program (SDSMP), when compared at 6 months to randomized control
      subjects, would demonstrate improvements in health status, health behaviors, and
      self-efficacy; and 2) whether SDSMP participants receiving monthly automated
      telephone reinforcement would maintain improvements at 18 months better than
      those not receiving reinforcement. RESEARCH DESIGN AND METHODS: A total of 567
      Spanish-speaking adults with type 2 diabetes were randomized to a usual-care
      control group or 6-week community-based, peer-led SDSMP. SDSMP participants were
      re-randomized to receive 15 months of automated telephone messages or no
      reinforcement. A1C was measured at baseline and 6 and 18 months. All other data
      were collected by self-administered questionnaires. RESULTS: At 6 months SDSMP
      participants compared with control subjects demonstrated improvements in A1C (
      0.4%), health distress, symptoms of hypo- and hyperglycemia, and self-efficacy (P
      < 0.05). At 18 months all improvements persisted (P < 0.05). SDSMP participants
      also demonstrated improvements in self-rated health and communication with
      physicians, had fewer emergency room visits (-0.18 visits in 6 months, P < 0.05),
      and trended toward fewer visits to physicians. At 18 months the only difference
      between reinforced and nonreinforced participants was increased glucose
      monitoring for the reinforcement group. CONCLUSIONS: The SDSMP demonstrated
      effectiveness in lowering A1C and improving health status. Reinforcement did not
      add to its effectiveness. Given the high needs of the Spanish-speaking
      population, the SDSMP deserves consideration for implementation.

PMID- 18096811
TI  - FreeStyle navigator continuous glucose monitoring system use in children with
      type 1 diabetes using glargine-based multiple daily dose regimens: results of a
      pilot trial Diabetes Research in Children Network (DirecNet) Study Group.

PMID- 18096812
TI  - Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5
      antagonists.
AB  - In addition to being an important receptor in leukocyte activation and
      mobilization, CCR5 is the essential coreceptor for human immunodeficiency virus
      (HIV). A large number of small-molecule CCR5 antagonists have been reported that
      show potent activities in blocking chemokine function and HIV entry. To
      facilitate the design and development of next generation CCR5 antagonists,
      docking models for major classes of CCR5 antagonists were created by using site
      directed mutagenesis and CCR5 homology modeling. Five clinical candidates:
      maraviroc, vicriviroc, aplaviroc, TAK-779, and TAK-220 were used to establish the
      nature of the binding pocket in CCR5. Although the five antagonists are very
      different in structure, shape, and electrostatic potential, they were able to fit
      in the same binding pocket formed by the transmembrane (TM) domains of CCR5. It
      is noteworthy that each antagonist displayed a unique interaction profile with
      amino acids lining the pocket. Except for TAK-779, all antagonists showed strong
      interaction with Glu283 in TM 7 via their central basic nitrogen. The fully
      mapped binding pocket of CCR5 is being used for structure-based design and lead
      optimization of novel anti-HIV CCR5 inhibitors with improved potency and better
      resistance profile.

PMID- 18096813
TI  - RBP-J, the transcription factor downstream of Notch receptors, is essential for
      the maintenance of vascular homeostasis in adult mice.
AB  - In adults, angiogenic abnormalities are involved in not only tumor growth but
      several human inherited diseases as well. It is unclear, however, concerning how
      the normal vascular structure is maintained and how angiogenesis is initiated in
      normal adults. Using the Cre-LoxP-mediated conditional gene deletion, we show in
      the present study that in adult mice disruption of the transcription factor
      recombination signal-binding protein Jkappa (RBP-J) in endothelial cells
      strikingly induced spontaneous angiogenesis in multiple tissues, including retina
      and cornea, as well as in internal organs, such as liver and lung. In a choroidal
      neovascularization model, which mimics the angiogenic process in tumor growth and
      age-related macular degeneration, RBP-J deficiency induced a more intensive
      angiogenic response to injury. This could be transmitted by bone marrow,
      indicating that RBP-J could modulate bone marrow-derived endothelial progenitor
      cells in adult angiogenesis. In addition, in the absence of RBP-J, proliferation
      of endothelial cells increased significantly, leading to accumulative vessel
      outgrowth. These findings suggest that in adults RBP-J-mediated Notch signaling
      may play an essential role in the maintenance of vascular homeostasis by
      repressing endothelial cell proliferation.

PMID- 18096814
TI  - Membrane-bound beta-amyloid oligomers are recruited into lipid rafts by a fyn
      dependent mechanism.
AB  - Recently published research indicates that soluble oligomers of beta-amyloid
      (Abeta) may be the key neurotoxic species associated with the progression of
      Alzheimer's disease (AD) and that the process of Abeta aggregation may drive this
      event. Furthermore, soluble oligomers of Abeta and tau accumulate in the lipid
      rafts of brains from AD patients through an as yet unknown mechanism. Using cell
      culture models we report a novel action of Abeta on neuronal plasma membranes
      where exogenously applied Abeta in the form of ADDLs can be trafficked on the
      neuronal membrane and accumulate in lipid rafts. ADDL-induced dynamic alterations
      in lipid raft protein composition were found to facilitate this movement. We show
      clear associations between Abeta accumulation and redistribution on the neuronal
      membrane and alterations in the protein composition of lipid rafts. In addition,
      our data from fyn(-/-) transgenic mice show that accumulation of Abeta on the
      neuronal surface was not sufficient to cause cell death but that fyn is required
      for both the redistribution of Abeta and subsequent cell death. These results
      identify fyn-dependent Abeta redistribution and accumulation in lipid rafts as
      being key to ADDL-induced cell death and defines a mechanism by which oligomers
      of Abeta and tau accumulate in lipid rafts.

PMID- 18096815
TI  - The human vomeronasal type-1 receptor family--detection of volatiles and cAMP
      signaling in HeLa/Olf cells.
AB  - The human genome harbors 5 remnant genes coding for vomeronasal type-1 receptors,
      compared with 187 of such receptors in mice. In rodents, vomeronasal type-1
      receptors are typically expressed in the vomeronasal organ. They are believed to
      be highly selective and sensitive pheromone detectors, as may be inferred from
      one receptor, V1rb2, responding to picomolar concentrations of the mouse
      pheromone 2-heptanone. Expression patterns, ligands, and signal transduction of
      human vomeronasal type-1 receptors have, however, remained largely obscure. Our
      aim was to deorphan and functionally characterize these 5 putative human
      pheromone receptors. Here, we report functional expression for all 5 receptors in
      HeLa/Olf cells. The recombinant, N-terminally tagged receptors expressed at the
      plasma membrane of HeLa/Olf cells and responded differentially to 19 of 140
      odorants in a combinatorial way. C9-C10 aliphatic alcohols or aldehydes emerged
      as the best agonists at submicromolar concentrations above human odorant
      thresholds. Surprisingly, and in contrast to mouse V1rb2, all human vomeronasal
      type-1 receptors activated cAMP signaling via G protein alphaolf, when expressed
      in HeLa/Olf cells. While a biological function of human vomeronasal type-1
      receptors is still elusive, our data show that their major functional
      characteristics are similar to those of odorant receptors.

PMID- 18096816
TI  - Heat-stable enterotoxin of Escherichia coli (STa) can stimulate duodenal HCO3(-)
      secretion via a novel GC-C- and CFTR-independent pathway.
AB  - The heat-stable enterotoxin of Escherichia coli (STa) is a potent stimulant of
      intestinal chloride and bicarbonate secretion. Guanylyl cyclase C (GC-C) has been
      shown to be the primary receptor involved in mediating this response. However,
      numerous studies have suggested the existence of an alternative STa-binding
      receptor. The aims of this study were to determine whether a non-GC-C receptor
      exists for STa and what is the functional relevance of this for intestinal
      bicarbonate secretion in mice. (125)I-STa-binding experiments were performed with
      intestinal mucosae from GC-C knockout (KO) and wild type (WT) mice. Subsequently,
      the functional relevance of an alternative STa-binding receptor was explored by
      examining STa-, uroguanylin-, and guanylin-stimulated duodenal bicarbonate
      secretion (DBS) in GC-C KO mice in vitro and in vivo. Significant (125)I-STa
      binding occurred in the proximal small intestines of GC-C KO and WT mice.
      Analysis of binding coefficients and pH dependence showed that (125)I-STa-binding
      in GC-C KO mice involved a receptor distinct from that of WT mice. Functionally,
      STa, uroguanylin, and guanylin all stimulated a significant increase in DBS in GC
      C KO mice. Uroguanylin- and guanylin-stimulated DBS were significantly inhibited
      by glibenclamide, but not by 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid
      (DIDS). However, STa-stimulated DBS was unaffected by glibenclamide but inhibited
      by DIDS. Taken together, our results suggest that alternative, non-GC-C,
      receptors likely exist for STa, uroguanylin, and guanylin in the intestines of
      mice. While uroguanylin- and guanylin-stimulated DBS are cystic fibrosis
      transmembrane conductance regulator (CFTR) dependent, STa-stimulated DBS is CFTR
      independent. Further understanding of this alternative receptor and its signaling
      pathway may provide important insights into rectification of intestinal
      bicarbonate secretion in cystic fibrosis.

PMID- 18096817
TI  - Agonist-stimulated endothelial nitric oxide synthase activation and vascular
      relaxation. Role of eNOS phosphorylation at Tyr83.
AB  - Tyr83 in endothelial nitric oxide synthase (eNOS) has been identified previously
      as a site of Src kinase-mediated phosphorylation of eNOS in bovine aortic
      endothelial cells (BAECs) that is phosphorylated in response to oxidant stress.
      In the present study, we have used a phospho-specific antibody to show that Tyr83
      in eNOS is also phosphorylated in both BAECs and intact blood vessel segments in
      response to treatment with a variety of different eNOS-activating agonists,
      including thapsigargin, vascular endothelial growth factor, bradykinin, ATP,
      sphingosine-1-phosphate, estrogen, angiopoietin, and acetylcholine. Agonist
      stimulation of eNOS Tyr83 phosphorylation as well as agonist stimulation of
      endothelial NO release in BAECs is blocked by Src kinase inhibition by either 4
      amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine (PP2) or by
      dominant negative Src. Mutation of Tyr83 to a nonphosphorylatable Phe blocks
      agonist stimulation of NO release from eNOS-reconstituted eNOS knockdown
      endothelial cells. Mutation of Tyr83 also attenuates agonist-induced relaxation
      of eNOS-reconstituted aortic rings from eNOS knockout mice. Phosphorylation of
      eNOS at Tyr83 thus appears to be a common covalent modification that is induced,
      not only by oxidant stress but also by other physiologically relevant
      extracellular signals known to be important in regulation of eNOS activity in
      vivo. Moreover, our results demonstrate an important role for Src-mediated
      phosphorylation of eNOS at Tyr83 in agonist stimulation of eNOS activation and
      vascular relaxation.

PMID- 18096818
TI  - Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction:
      linking mitochondrial oxidative damage and vascular endothelial dysfunction.
AB  - Mitochondrial dysfunction is a prominent feature of most cardiovascular diseases.
      Angiotensin (Ang) II is an important stimulus for atherogenesis and hypertension;
      however, its effects on mitochondrial function remain unknown. We hypothesized
      that Ang II could induce mitochondrial oxidative damage that in turn might
      decrease endothelial nitric oxide (NO.) bioavailability and promote vascular
      oxidative stress. The effect of Ang II on mitochondrial ROS, mitochondrial
      respiration, membrane potential, glutathione, and endothelial NO. was studied in
      isolated mitochondria and intact bovine aortic endothelial cells using electron
      spin resonance, dihydroethidium high-performance liquid chromatography -based
      assay, Amplex Red and cationic dye fluorescence. Ang II significantly increased
      mitochondrial H2O2 production. This increase was blocked by preincubation of
      intact cells with apocynin (NADPH oxidase inhibitor), uric acid (scavenger of
      peroxynitrite), chelerythrine (protein kinase C inhibitor), N(G)-nitro-L-arginine
      methyl ester (nitric oxide synthase inhibitor), 5-hydroxydecanoate (mitochondrial
      ATP-sensitive potassium channels inhibitor), or glibenclamide. Depletion of
      p22(phox) subunit of NADPH oxidase with small interfering RNA also inhibited Ang
      II-mediated mitochondrial ROS production. Ang II depleted mitochondrial
      glutathione, increased state 4 and decreased state 3 respirations, and diminished
      mitochondrial respiratory control ratio. These responses were attenuated by
      apocynin, 5-hydroxydecanoate, and glibenclamide. In addition, 5-hydroxydecanoate
      prevented the Ang II-induced decrease in endothelial NO. and mitochondrial
      membrane potential. Therefore, Ang II induces mitochondrial dysfunction via a
      protein kinase C-dependent pathway by activating the endothelial cell NADPH
      oxidase and formation of peroxynitrite. Furthermore, mitochondrial dysfunction in
      response to Ang II modulates endothelial NO. and generation, which in turn has
      ramifications for development of endothelial dysfunction.

PMID- 18096819
TI  - Thyroid hormone regulates developmental titin isoform transitions via the
      phosphatidylinositol-3-kinase/ AKT pathway.
AB  - Titins, giant sarcomere proteins with major mechanical/signaling functions, are
      expressed in 2 main isoform classes in the mammalian heart: N2B (3000 kDa) and
      N2BA (>3200 kDa). A dramatic isoform switch occurs during cardiac development,
      from fetal N2BA titin (3700 kDa) expressed before birth to a mix of smaller
      N2BA/N2B isoforms found postnatally; adult rat hearts almost exclusively have N2B
      titin. The isoform switch, which can be reversed in chronic human heart failure,
      alters myocardial distensibility and mechanosignaling. Here we determined factors
      regulating this switch using, as a model system, primary cardiomyocyte cultures
      prepared from embryonic rats. In standard culture, the mean N2B percentage
      initially was 14% and increased by approximately 60% within 1 week, resembling
      the in vivo switching. The titin isoform transition was independent of endothelin
      1-induced myocyte hypertrophy and was not altered by pacing, contractile arrest,
      or cell stretch; however, it was modestly impaired by decreasing substrate
      rigidity and strongly dependent on serum components. Angiotensin II significantly
      promoted the transition. The mean N2B proportion in 1-week-old cultures dropped
      20% to 25% in hormone-reduced medium, but addition of 3,5,3'-triiodo-l-thyronine
      (T3) nearly restored the proportion to that found in standard culture. This T3
      effect was not prevented by bisphenol A, a specific inhibitor of the classic
      genomic pathway of T3 action. In contrast, the titin switch could be stalled by
      the phosphatidylinositol 3-kinase inhibitor LY294002, which decreased the
      proportion of N2B mRNA transcripts within hours and suppressed a rapid T3-induced
      increase in Akt phosphorylation. Also, angiotensin II, but not endothelin-1 or
      cell stretch, enhanced Akt phosphorylation. Thus, although matrix stiffness
      modulates developmental titin isoform transitions, these transitions are mainly
      regulated through phosphatidylinositol 3-kinase/Akt-dependent signaling triggered
      particularly by T3 via a rapid action pathway.

PMID- 18096820
TI  - Functional roles of a Ca2+-activated K+ channel in atrioventricular nodes.
AB  - Since the first description of the anatomical atrioventricular nodes (AVNs), a
      large number of studies have provided insights into the heterogeneity of the
      structure as well as a repertoire of ion channel proteins that govern this
      complex conduction pathway between the atria and ventricles. These studies have
      revealed the intricate organization of multiple nodal and nodal-like myocytes
      contributing to the unique electrophysiology of the AVN in health and diseases.
      On the other hand, information regarding the contribution of specific ion
      channels to the function of the AVN remains incomplete. We reason that the
      identification of AVN-specific ion channels may provide a more direct and
      rational design of therapeutic target in the control of AVN conduction in atrial
      flutter/fibrillation, one of the most common arrhythmias seen clinically. In this
      study, we took advantage of 2 genetically altered mouse models with
      overexpression or null mutation of 1 of a small conductance Ca2+-activated K+
      channel isoform, SK2 channel, and demonstrated robust phenotypes of AVN
      dysfunction in these experimental models. Overexpression of SK2 channels results
      in the shortening of the spontaneous action potentials of the AVN cells and an
      increase in the firing frequency. On the other hand, ablation of the SK2 channel
      results in the opposite effects on the spontaneous action potentials of the AVN.
      Furthermore, we directly documented the expression of SK2 channel in mouse AVN
      using multiple techniques. The new insights may have important implications in
      providing novel drug targets for the modification of AVN conduction in the
      treatment of atrial arrhythmias.

PMID- 18096821
TI  - Dual regulation of cofilin activity by LIM kinase and Slingshot-1L phosphatase
      controls platelet-derived growth factor-induced migration of human aortic smooth
      muscle cells.
AB  - Platelet-derived growth factor (PDGF) plays a central role in vascular healing,
      atherosclerosis, and restenosis, partly by stimulating vascular smooth muscle
      cell (VSMC) migration. Migration requires rapid turnover of actin filaments,
      which is partially controlled by cofilin. Although cofilin is negatively
      regulated by Ser3 phosphorylation, the upstream signaling pathways have not been
      defined, nor has its role in VSMC migration been studied. We hypothesized that
      PDGF-induced migration of VSMCs involves cofilin activation and that this is
      regulated by the serine kinase LIM kinase (LIMK) and the novel phosphatase
      Slingshot (SSH)1L. In human VSMCs, stimulation with PDGF increased G-actin
      incorporation into the actin cytoskeleton. PDGF transiently activated the cofilin
      kinase, LIMK, with a peak at 5 minutes. However, cofilin was dephosphorylated
      between 5 and 45 minutes, with a maximum of 43+/-5% dephosphorylation at 30
      minutes, suggesting that PDGF also activates a cofilin phosphatase. We found that
      VSMCs express SSH1L, which is induced and activated (564+/-73 versus 1021+/-141
      picomoles of PO(4); P=0.015) by PDGF. Of importance, small interfering RNA
      directed against SSH1L blocked cofilin dephosphorylation and decreased migration
      (528+/-33 versus 318+/-25 cells/field; P<0.01). Taken together, our results
      suggest that PDGF participates in actin dynamics by dual regulation of cofilin
      activity via LIMK and SSH1L.

PMID- 18096822
TI  - The cell cycle factor E2F-1 activates Bnip3 and the intrinsic death pathway in
      ventricular myocytes.
AB  - The cell cycle factor E2F-1 is known to regulate a variety of cellular processes
      including apoptosis. Previously we showed that disruption of Rb-E2F-1 complexes
      provoked apoptosis of postmitotic adult and neonatal ventricular myocytes;
      however, the underlying mechanism was undetermined. In this report, we show that
      E2F-1 provokes cell death of ventricular myocytes through a mechanism that
      directly impinges on the intrinsic death pathway. Furthermore, we show
      mechanistically that the hypoxia-inducible death factor Bnip3 is a direct
      transcriptional target of E2F-1 that is necessary and sufficient for E2F-1
      induced cell death. Expression of E2F-1 resulted in a 4.9-fold increase (P<0.001)
      in nucleosomal DNA fragmentation and cell death by Hoechst 33258 dye and vital
      staining. E2F-1 provoked mitochondrial perturbations that were consistent with
      permeability transition pore opening. As determined by quantitative real-time PCR
      analysis, a 6.2-fold increase (P<0.001) in endogenous Bnip3 gene transcription
      was observed in cells expressing wild-type E2F-1 but not in cells expressing a
      mutation of E2F-1 defective for DNA binding. Rb, the principle regulator of
      cellular E2F-1 activity, was proteolytically cleaved and inactivated in
      ventricular myocytes during hypoxia. Consistent with the proteolytic cleavage of
      Rb, chromatin immunoprecipitation analysis revealed increased binding of E2F-1 to
      the Bnip3 promoter during hypoxia, a finding concordant with the induction of
      Bnip3 gene transcription. The Bnip3 homolog Nix/Bnip3L was unaffected in
      ventricular myocytes by either E2F-1 or hypoxia. Genetic knockdown of E2F-1 or
      expression of a caspase-resistant form of Rb suppressed basal and hypoxia
      inducible Bnip3 gene transcription. Loss-of-function mutations of Bnip3 defective
      for mitochondrial membrane insertion or small interference RNA directed against
      Bnip3 suppressed cell death signals elicited by E2F-1. To our knowledge, the data
      provide the first direct evidence that activation of the intrinsic mitochondrial
      death pathway by E2F-1 is mutually dependent on and obligatorily linked to the
      transcriptional activation of Bnip3.

PMID- 18096823
TI  - CaMKII-delta isoform regulation of neointima formation after vascular injury.
AB  - OBJECTIVE: The purpose of this study was to test the function of the
      calcium/calmodulin-dependent protein kinase II delta2 isoform (CaMKIIdelta2) in
      regulating vascular smooth muscle (VSM) cell proliferation and migration in
      response to vascular injury. METHODS AND RESULTS: CaMKII isoform content was
      assessed in rat carotid arteries after balloon angioplasty-induced injury by
      Western blotting with isoform specific antibodies. Within 3 days after injury, a
      significant increase in CaMKIIdelta2 and decrease in CaMKIIgamma isoform content
      was observed in both medial smooth muscle and adventitial fibroblasts. Neointimal
      VSM cells expressed primarily the delta2 isoform. Incubation of the injured
      vessel with adenovirus encoding siRNA targeting CaMKIIdelta isoforms prevented
      upregulation of the delta2 isoform in the media and adventitia; inhibited cell
      proliferation assessed by PCNA expression in both layers and markedly inhibited
      neointima formation and adventitial thickening. CONCLUSIONS: CaMKIIdelta2 is
      specifically induced in VSM and adventitial fibroblasts during the response of an
      artery to injury and is a positive regulator of proliferation and migration in
      the vessel wall contributing to neointima formation and vascular remodeling. This
      provides a potential mechanism for Ca2+-dependent regulation of VSM and
      myofibroblast proliferation and migration in response to vascular injury or
      disease.

PMID- 18096825
TI  - Femoral atherosclerosis in heterozygous familial hypercholesterolemia: influence
      of the genetic defect.
AB  - OBJECTIVE: The purpose of this study was to assess femoral atherosclerosis by
      ultrasound in patients with molecularly defined heterozygous familial
      hypercholesterolemia (FH) in comparison with matched control subjects and in
      relation to mutational class in the LDL receptor and apolipoprotein B (APOB)
      genes. METHODS AND RESULTS: Femoral intima-media thickness (IMT) and plaque were
      evaluated in 146 FH patients carrying null alleles (n=48), defective-receptor
      alleles (n=62), undetermined-function alleles (n=25), or APOB defects (n=11) and
      in 193 healthy subjects. Twenty-three patients had coronary heart disease (CHD).
      The frequency of both tendon xanthomas and CHD was approximately 2-fold higher
      and average LDL cholesterol was 30 mg/dL higher in null-allele genotype compared
      with receptor-defective mutations. All femoral measurements were increased in FH
      patients versus controls (P<0.001), and null-allele mutations showed higher age-,
      sex-, and LDL cholesterol-adjusted maximum IMT than receptor-defective or APOB
      defects (P for trend, 0.001). By multivariate analysis, independent associations
      of mean IMT, a measure of early atherosclerosis, were age, LDL cholesterol, sex,
      and systolic blood pressure. Age, null-allele genotype, sex, and smoking
      explained 42% of the variability of maximum IMT, a measure of advanced
      atherosclerosis. CONCLUSIONS: FH patients have increased femoral IMT in relation
      to mutational class. The findings support the usefulness of genetic testing in FH
      beyond securing the diagnosis.

PMID- 18096824
TI  - Plasminogen activator inhibitor-1 polymorphism (4G/5G) predicts recurrence in
      nonhyperlipidemic postinfarction patients.
AB  - OBJECTIVE: Nonhyperlipidemic postinfarction patients are at high risk for
      recurrent coronary events by virtue of incident myocardial infarction (MI);
      however, few studies assess risk beyond incident MI. The aim of this study was to
      assess such risk as a function of 37 atherosclerosis-associated genetic
      polymorphisms and 17 blood marker variables. METHODS AND RESULTS: Screening of
      polymorphisms in nonhyperlipidemic postinfarction patients revealed significant
      risk only for the 4G/5G insertion/deletion polymorphism in the promoter of the
      plasminogen-activator inhibitor-1 (PAI-1) gene. Outcome event mapping, an
      exploratory data analysis tool, was then applied to define a subgroup (182
      patients from total study population of 846 nondiabetic patients) exhibiting
      maximal functional dependence of risk on the PAI-1 polymorphism. Cox
      multivariable regression analyses within the subgroup adjusted for significant
      clinical covariates and medication use as a function of the PAI-1 polymorphism
      and 17 atherosclerosis-associated blood markers revealed significant risk for
      patients homozygous for the 4G allele (hazard ratio 4.30, 95% CI 1.98 to 9.33,
      P=0.00023), and lack of significant risk-association with any blood marker.
      CONCLUSIONS: In a subgroup of normolipidemic postinfarction patients, only the
      PAI-1 4G/5G polymorphism was associated with recurrent risk from a set of
      atherosclerosis-associated genetic polymorphisms and blood markers.

PMID- 18096826
TI  - Regulation of vasculogenesis by platelet-mediated recruitment of bone marrow
      derived cells.
AB  - Bone marrow-derived cells contribute to physiological and pathological vascular
      remodeling throughout ontogenesis and adult life. During tissue regeneration and
      tumor growth, the release of cytokines and chemokines mediates the recruitment of
      hematopoietic and endothelial progenitor cells that contribute to the assembly of
      neovessels. Current evidence implies that platelets contribute structurally and
      instructively to vascular remodeling. Platelets adhere almost immediately to
      exposed or activated endothelium, and they are major storage and delivery
      vehicles for pro- and antiangiogenic growth factors including VEGF-A and
      thrombospondin (TSP), and cytokines and chemokines, such as stromal-derived
      factor 1 (SDF-1). By site-specific deployment of these factors, platelets
      orchestrate the local angiogenic stimulus within a tissue and direct the
      recruitment and differentiation of circulating bone marrow-derived cells. These
      insights have profound clinical implications; inhibition of platelet-deployed
      growth factors or their receptors may be an effective strategy to block tumor
      growth, whereas activation of these pathways may be used to accelerate
      revascularization and tissue regeneration.

PMID- 18096827
TI  - Laminar shear stress regulates liver X receptor in vascular endothelial cells.
AB  - OBJECTIVE: The liver X receptors (LXRs) regulate a set of genes involved in lipid
      metabolism and reverse cholesterol transport. We investigated the mechanism by
      which shear stress regulates LXR in vascular endothelial cells (ECs). METHODS AND
      RESULTS: Western blot showed that the protein level of LXRalpha and its target
      ABCA1 in the mouse thoracic aorta was higher than that in the aortic arch. As
      well, the mRNA level of LXR and its target genes ABCA1, ABCG1, ApoE, and LPL in
      the thoracic aorta was higher. In vitro, bovine aortic ECs were subjected to a
      steady laminar flow (12 dyne/cm2). The expressions of LXR and the LXR-mediated
      transcription were increased by laminar shear stress. Laminar flow increased LXR
      ligand binding and the gene expression of sterol 27-hydroxylase (CYP27), which
      suggests an increased level of LXR ligand in ECs. This effect was attenuated by
      LXRalpha and CYP27 RNAi. The decrease of LXR in the aorta of PPARgamma+/- mice
      and that of C57 mice fed with PPARgamma antagonist suggest the involvement of
      PPARgamma in the LXR induction by flow. CONCLUSIONS: Laminar flow increases LXR
      function via a PPARgamma-CYP27 dependent mechanism, which reveals an
      atheroprotective role for laminar flow exerting on endothelium.

PMID- 18096828
TI  - C-reactive protein inhibits cholesterol efflux from human macrophage-derived foam
      cells.
AB  - OBJECTIVE: The objective of this study was to determine the effects and potential
      mechanisms of C-reactive protein (CRP) on cholesterol efflux from human
      macrophage foam cells, which may play a critical role in atherogenesis. METHODS
      AND RESULTS: Human THP-1 monocytes and peripheral blood mononuclear cells (PBMCs)
      were preincubated with acetylated LDL and [3H]-cholesterol to form foam cells,
      which were then treated with apolipoprotein A-I (apoA-I) or HDL for cholesterol
      efflux assay. Clinically relevant concentrations of CRP significantly reduced
      cholesterol efflux from THP-1 and PBMCs to apoA-I or HDL. CRP significantly
      decreased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1)
      and ABCG1, whereas it increased superoxide anion production. Furthermore, CRP
      substantially activated ERK1/2 in THP-1-derived foam-like cells. Reducing
      superoxide anion by antioxidant seleno-L-methionine or SOD mimetic (MnTBAP)
      effectively abolished the CRP-induced decrease in cholesterol efflux and the
      expression of ABCA1 and ABCG1. Inhibiting ERK1/2 activation by its specific
      inhibitor PD98059 or by a dominant negative mutant of ERK2 could also block CRPs
      action on THP-1 cells. CONCLUSIONS: CRP inhibits cholesterol efflux from human
      foam cells derived from THP-1 and PBMCs in vitro though oxidative stress, ERK1/2
      activation, and downregulation of intracellular cholesterol transport molecules
      ABCA1 and ABCG1.

PMID- 18096829
TI  - Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression
      through macrophage activation and monocyte chemoattraction.
AB  - OBJECTIVE: Galectin-3 (Gal-3) is a 26-kDa lectin known to regulate many aspects
      of inflammatory cell behavior. We assessed the hypothesis that increased levels
      of Gal-3 contribute to atherosclerotic plaque progression by enhancing monocyte
      chemoattraction through macrophage activation. METHODS AND RESULTS: Gal-3 was
      found to be upregulated in unstable plaque regions of carotid endarterectomy
      (CEA) specimens compared with stable regions from the same patient (3.2-fold,
      P<0.05) at the mRNA (n=12) and (2.3-fold, P<0.01) at the protein level (n=9).
      Analysis of aortic tissue from ApoE-/- mice on a high fat diet (n=14) and wild
      type controls (n=9) showed that Gal-3 mRNA and protein levels are elevated by
      16.3-fold (P<0.001) and 12.2-fold (P<0.01) and that Gal-3 staining colocalizes
      with macrophages. In vitro, conditioned media from Gal-3-treated human
      macrophages induced an up to 6-fold increase in human monocyte chemotaxis
      (P<0.01, ANOVA), an effect that was reduced by 66 and 60% by Pertussis Toxin
      (PTX) and the Vaccinia virus protein 35K, respectively. Microarray analysis of
      human macrophages and subsequent qPCR validation confirmed the upregulation of CC
      chemokines in response to Gal-3 treatment. CONCLUSIONS: Our data suggest that Gal
      3 is both a marker of atherosclerotic plaque progression and a central
      contributor to the pathology by amplification of key proinflammatory molecules.

PMID- 18096830
TI  - Iliac venous stenting: antithrombotic efficacy of PD0348292, an oral direct
      Factor Xa inhibitor, compared with antiplatelet agents in pigs.
AB  - OBJECTIVE: The clinical use of venous stents is increasing dramatically. Although
      antiplatelet agents are required for arterial stent patency, optimal thrombo
      prophylaxis after venous stenting remains undefined. To address this issue,
      PD0348292, a direct Factor Xa inhibitor, was compared with antiplatelet therapy
      in a porcine venous stent model. METHODS AND RESULTS: Four hours before stent
      deployment, pigs (n=5 to 6 per group) received oral PD0348292 at 0.4, 0.9, 4.3
      mg/kg, or 0.4 mg/kg plus aspirin (325 mg). Aspirin, clopidogrel (75 mg), aspirin
      plus clopidogrel, or vehicle (n=10) were administered daily for 2 days before the
      procedure. Two hours after stent placement, thrombi were quantified by autologous
      (111)In-platelet content and weights. Thrombus weight and platelet deposition
      were significantly reduced by PD0348292 at 0.4 (49+/-79 mg and 110+/
      145x10(6)/cm2), 0.9 (5+/-6 mg and 107+/-128x10(6)/cm2), 4.3 mg/kg (0+/-0 mg and
      87+/-125x10(6)/cm2), and PD348292 plus aspirin (20+/-40 mg and 157+/
      70x10(6)/cm2) compared with vehicle (402+/-226 mg; 584+/-454x10(6)/cm2). Despite
      prolonging bleeding times and inhibiting platelet aggregation, neither aspirin
      (567+/-683 mg and 533+/-622x10(6)/cm2), clopidogrel (404+/-349 mg and 178+/
      101x10(6)/cm2), nor aspirin plus clopidogrel (247+/-261 mg and 231+/
      266x10(6)/cm2) significantly decreased stent thrombosis. CONCLUSIONS: PD0348292
      completely inhibited thrombosis after venous stenting. Platelet accretion in
      these venous thrombi appear to involve pathways distinct from arachidonate
      metabolism or ADP P2Y12 receptor activation.

PMID- 18096831
TI  - Oleate induces a myofibroblast-like phenotype in mesangial cells.
AB  - OBJECTIVE: High circulating free fatty acids, commonly associated with obesity
      and insulin resistance, impair structure and function of the microvasculature.
      However, the mechanisms by which fatty acids cause microvascular remodeling are
      unclear. Using the mesangial cell model of microvascular pericytes, we
      demonstrate that the monounsaturated free fatty acid oleate induces a
      myofibroblast phenotype, an important cell fate transition in fibrotic remodeling
      of the extracellular matrix. MATERIALS AND RESULTS: Oleate induced a time- and
      dose-dependent increase in secretion of collagen I and fibronectin. Oleate also
      induced the myofibroblast phenotype markers alpha smooth muscle actin and ED-A
      fibronectin, and the magnitude of marker protein expression was similar to that
      for transforming growth factor (TGF)-beta. Oleate raised TGF-beta secretion 2.2
      fold, and processing of latent to bioactive TGF-beta was also elevated. Oleate
      rapidly stimulated extracellular signal-regulated kinase1/2, and a
      pharmacological MEK inhibitor blocked TGF-beta secretion and conversion to the
      myofibroblast phenotype. A neutralizing TGF-beta antibody and a TGF-beta receptor
      kinase inhibitor blocked oleate-induced collagen I, alpha smooth muscle actin,
      and ED-A fibronectin, suggesting that oleate-stimulated TGF-beta was necessary
      for inducing myofibroblasts. CONCLUSIONS: Collectively, these results demonstrate
      that oleate can induce a myofibroblast phenotype in mesangial cells, which
      suggests a mechanism whereby elevated free fatty acids might promote
      microvascular remodeling in vivo.

PMID- 18096832
TI  - Factors associated with the decision to hospitalize patients after transient
      ischemic attack before publication of prediction rules.
AB  - BACKGROUND AND PURPOSE: One important criterion for hospitalizing patients after
      transient ischemic attack (TIA) is the short-term risk of stroke. Before
      publication of prediction rules for stroke after TIA, physician judgment was
      required to make a decision about hospitalization. We sought to identify factors
      associated with the decision to admit patients with TIA from the emergency
      department (ED) and to see whether those at highest risk of stroke were selected
      for admission. METHODS: All patients diagnosed with TIA in the ED of 16 hospitals
      in the Kaiser-Permanente Medical Care Plan over a 1-year period before
      publication of prediction rules were included (n=1707). Risk of subsequent stroke
      was stratified according to a validated prediction rule (ABCD(2) score), and the
      decision to admit was correlated with these risk scores. Factors associated with
      admission in univariate analysis were included in a logistic regression model.
      RESULTS: Overall, 243 patients with TIA (14%) were admitted. Admission weakly
      correlated with the ABCD(2) score (rank biserial R(2)=0.036; 10.0% at low 2-day
      risk of stroke admitted versus 20.3% at high risk). Seven variables were
      independently associated with a decision to admit after TIA: prior TIA, speech
      impairment, weakness, gait disturbance, history of atrial fibrillation, symptoms
      on arrival to ED, and use of ticlopidine. CONCLUSIONS: In this cohort of patients
      with TIA, the decision to admit was weakly correlated with risk of subsequent
      stroke as measured by the ABCD(2) score, and several risk factors for stroke were
      not important for the decision to admit. Before publication of prediction rules
      for stroke after TIA, physicians were not identifying the majority of patients at
      highest risk of stroke for admission.

PMID- 18096833
TI  - Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene
      as a risk factor for cerebral venous thrombosis.
AB  - BACKGROUND AND PURPOSE: Plasma glutathione peroxidase (GPx-3) is a major
      antioxidant enzyme in plasma and the extracellular space that scavenges reactive
      oxygen species produced during normal metabolism or after oxidative insult. A
      deficiency of this enzyme increases extracellular oxidant stress, promotes
      platelet activation, and may promote oxidative posttranslational modification of
      fibrinogen. We recently identified a haplotype (H(2)) in the GPx-3 gene promoter
      that increases the risk of arterial ischemic stroke among children and young
      adults. METHODS: The aim of this study is to identify possible relationships
      between promoter haplotypes in the GPx-3 gene and cerebral venous thrombosis
      (CVT). We studied the GPx-3 gene promoter from 23 patients with CVT and 123 young
      controls (18 to 45 years) by single-stranded conformational polymorphism and
      sequencing analysis. RESULTS: Over half of CVT patients (52.1%) were heterozygous
      (H(1)H(2)) or homozygous (H(2)H(2)) carriers of the H(2) haplotype compared with
      12.2% of controls, yielding a more than 10-fold independent increase in the risk
      of CVT (OR=10.7; 95% CI, 2.70 to 42.36; P<0.0001). Among women, the interaction
      of the H(2) haplotype with hormonal risk factors increased the OR of CVT to
      almost 70 (P<0.0001). CONCLUSIONS: These findings show that a novel GPx-3
      promoter haplotype is a strong, independent risk factor for CVT. As we have
      previously shown that this haplotype is associated with a reduction in
      transcriptional activity, which compromises antioxidant activity and
      antithrombotic benefits of the enzyme, these results suggest that a deficiency of
      GPx-3 leads to a cerebral venous thrombophilic state.

PMID- 18096834
TI  - Medical complications in a comprehensive stroke unit and an early supported
      discharge service.
AB  - BACKGROUND AND PURPOSE: The aims of the study were to examine the frequency and
      timing of predefined medical complications in unselected acute stroke patients
      treated in an acute comprehensive stroke unit and an early supported discharge
      service. METHODS: Four hundred eighty-nine acute stroke patients were included
      and followed up with assessments of 16 prespecified complications during the
      first week. Two hundred forty-four of the patients were randomly allocated to a 3
      month follow-up. RESULTS: During the first week, 312 of 489 patients (63.8%)
      experienced 1 or more complications. The most common complications were pain in
      117 patients (23.9%), temperature >or=38 degrees C in 116 (23.7%), progressing
      stroke in 90 (18.4%), urinary tract infection in 78 (16.0%), troponin T elevation
      without criteria of myocardial infarction in 57 (11.7%), chest infections in 55
      (11.2%), nonserious falls in 36 (7.4%), and myocardial infarction in 22 (4.5%),
      whereas stroke recurrence, seizure, deep venous thrombosis, pulmonary embolism,
      shoulder pain, serious falls, other infections, and pressure sores were each
      present in <or=2.5% of patients. During the 3-month follow-up, 201 of 244
      patients (82.4%) experienced at least 1 complication, the most common of which
      was pain, which occurred in 134 patients (53.3%), followed by urinary tract
      infection in 68 (27.9%) and nonserious falls in 61 (25.0%). The severity of
      stroke on admission was the most important risk factor for developing
      complications. CONCLUSIONS: This is the first study of complications in
      unselected acute stroke patients treated in a comprehensive stroke unit and early
      supported discharge service and shows that pain, progressing stroke, infections,
      myocardial infarction, and falls are common complications, whereas others occur
      infrequently. Most complications occur during the first 4 days, and stroke
      severity is the most important risk factor.

PMID- 18096835
TI  - Edaravone attenuates brain edema and neurologic deficits in a rat model of acute
      intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Our previous studies have demonstrated that oxidative DNA
      injury occurs in the brain after intracerebral hemorrhage (ICH). We therefore
      examined whether edaravone, a free-radical scavenger, could reduce ICH-induced
      brain injury. METHODS: These experiments used pentobarbital-anesthetized, male
      Sprague-Dawley rats that received an infusion of either 100 microL autologous
      whole blood (ICH), FeCl(2), or thrombin into the right basal ganglia. The rats
      were humanely killed 24 hours later. There were 4 sets of experiments. In the
      first, the dose-dependent effects of edaravone on ICH-induced brain injury were
      examined by measuring brain edema and neurologic deficits. In the second set,
      apurinic/apyrimidinic abasic sites and 8-hydroxyl-2'-deoxyguanosine, which are
      hallmarks of DNA oxidation, were investigated after treatment for ICH. In the
      third, the effect of delayed treatment with edaravone on ICH-induced injury was
      determined, whereas the fourth examined the effects of edaravone on iron- and
      thrombin-induced brain injury. RESULTS: Systemic administration of edaravone
      immediately or 2 hours after ICH reduced brain water content 24 hours after ICH
      compared with vehicle (P<0.05). Edaravone treatment immediately or 2 hours after
      ICH also ameliorated neurologic deficits (P<0.05). Edaravone also attenuated ICH
      induced changes in apurinic/apyrimidinic abasic sites and 8-hydroxyl-2'
      deoxyguanosine and reduced iron- and thrombin-induced brain injury. CONCLUSIONS:
      Edaravone attenuates ICH-induced brain edema, neurologic deficits, and oxidative
      injury. It also reduces iron- and thrombin-induced brain injury. These results
      suggest that edaravone is a potential therapeutic agent for ICH.

PMID- 18096836
TI  - The relationship between leptin:adiponectin ratio and carotid intima-media
      thickness in asymptomatic females.

PMID- 18096837
TI  - Splinting poststroke: the jury is still out.

PMID- 18096838
TI  - Targeting stroke awareness public campaigns.

PMID- 18096839
TI  - Association of adiponectin with cerebrovascular disease: a nested case-control
      study.
AB  - BACKGROUND AND PURPOSE: Even though adiponectin is associated with many
      traditional cardiovascular risk factors, studies assessing the association
      between adiponectin and cerebrovascular disease (CVD) are scarce. We assessed the
      odds of CVD at different plasma levels of adiponectin. METHODS: A nested case
      control study was conducted involving 5243 subjects, drawn from 12 490 subjects
      of the Jichi Medical School Cohort Study, whose blood samples had been drawn
      between 1992 and 1995. Over an average of 9.7 years of follow-up, through 2005,
      179 patients with cerebrovascular events were identified, in addition to 630
      controls matched for age, sex, and community (total n=809). Odds ratios were
      estimated relative to the highest quartile of adiponectin level. RESULTS: There
      was neither a significant difference in the odds of stroke between the lowest and
      highest adiponectin quartiles, nor a significant linear trend toward a reduced
      risk of stroke at higher adiponectin levels. These results did not change after
      excluding participants with diabetes, impaired glucose metabolism, or metabolic
      syndrome. The odds of ischemic stroke in the lowest quartile were significantly
      higher than in the highest quartile, when adjusted for age and sex (OR 2.04 [95%
      CI, 1.09 to 3.80]). However, the odds failed to achieve statistical significance
      when adjusted further for other cardiovascular risk factors. Again exclusion of
      subjects with diabetes, impaired glucose metabolism, or metabolic syndrome did
      not alter results. CONCLUSIONS: Adiponectin levels are not independently
      associated with stroke or brain infarction. The use of adiponectin as a
      cerebrovascular disease predictor may be premature.

PMID- 18096840
TI  - Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial.
AB  - BACKGROUND AND PURPOSE: Hyperglycemia may worsen brain injury during acute
      cerebral infarction. We tested the feasibility and tolerability of aggressive
      hyperglycemia correction with intravenous insulin compared with usual care during
      acute cerebral infarction. METHODS: We conducted a randomized, multicenter,
      blinded pilot trial for patients with cerebral infarction within 12 hours after
      onset, a baseline glucose value >or=8.3 mmol/L (>or=150 mg/dL), and a National
      Institutes of Health Stroke Scale score of 3 to 22. Patients were randomized 2:1
      to aggressive treatment with continuous intravenous insulin or subcutaneous
      insulin QID as needed (usual care). Target glucose levels were <7.2 mmol/L (<130
      mg/dL) in the aggressive-treatment group and <11.1 mmol/L (<200 mg/dL) in the
      usual-care group. Glucose was monitored every 1 to 2 hours, and the protocol
      treatments continued for up to 72 hours. Final clinical outcomes were assessed at
      3 months. RESULTS: We randomized 46 patients (31 to aggressive treatment and 15
      to usual care). All patients in the aggressive-treatment group and 11 (73%) in
      the usual-care group had diabetes (P=0.008). Glucose levels were significantly
      lower in the aggressive-treatment group throughout protocol treatment (7.4 vs
      10.5 mmol/L [133 vs 190 mg/dL], P<0.001). Hypoglycemia <3.3 mmol/L (<60 mg/dL)
      occurred only in the aggressive-treatment group (11 patients, 35%), 4 (13%) of
      whom had brief symptoms, including only 1 (3%) neurologic. Final clinical
      outcomes were nonsignificantly better in the aggressive-treatment group.
      CONCLUSIONS: The intravenous insulin protocol corrected hyperglycemia during
      acute cerebral infarction significantly better than usual care without major
      adverse events and should be investigated in a clinical efficacy trial.

PMID- 18096841
TI  - Neurological signs in relation to type of cerebrovascular disease in vascular
      dementia.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to describe the prevalence of a
      number of neurological signs in a large population of patients with vascular
      dementia (VaD) and to compare the relative frequency of specific neurological
      signs dependent on type of cerebrovascular disease. METHODS: Seven hundred six
      patients with VaD (NINDS-AIREN) were included from a large multicenter clinical
      trial (registration number NCT00099216). At baseline neurological examination,
      the presence of 16 neurological signs was assessed. Based on MRI, patients were
      classified as having large vessel VaD (18%; large territorial or strategical
      infarcts on MRI), small vessel VaD (74%; white matter hyperintensities [WMH],
      multiple lacunes, bilateral thalamic lesions on MRI), or a combination of both
      (8%). RESULTS: A median number of 4.5 signs per patient was presented (maximum
      16). Reflex asymmetry was the most prevalent symptom (49%), hemianopia was most
      seldom presented (10%). Measures of small vessel disease were associated with an
      increased prevalence of dysarthria, dysphagia, parkinsonian gait disorder,
      rigidity, and hypokinesia and as well to hemimotor dysfunction. By contrast, in
      the presence of a cerebral infarct, aphasia, hemianopia, hemimotor dysfunction,
      hemisensory dysfunction, reflex asymmetry, and hemiplegic gait disorder were more
      often observed. CONCLUSIONS: The specific neurological signs demonstrated by
      patients with VaD differ according to type of imaged cerebrovascular disease.
      Even in people who meet restrictive VaD criteria, small vessel disease is often
      seen with more subtle signs, including extrapyramidal signs, whereas large vessel
      disease is more often related to lateralized sensorimotor changes and aphasia.

PMID- 18096842
TI  - Comparison of intraarterial and intravenous thrombolysis for ischemic stroke with
      hyperdense middle cerebral artery sign.
AB  - BACKGROUND AND PURPOSE: It is unclear whether intraarterial (IAT) or intravenous
      (IVT) thrombolysis is more effective for ischemic stroke with hyperdense middle
      cerebral artery sign (HMCAS) on computed tomography (CT). The aim of this study
      was to compare IAT and IVT in stroke patients with HMCAS. METHODS: Comparison of
      data from 2 stroke units with similar management of stroke associated with HMCAS,
      except that 1 unit performed IAT with urokinase and the other IVT with
      plasminogen activator. Time to treatment was up to 6 hours for IAT and up to 3
      hours for IVT. Outcome was measured by mortality and the modified Rankin Scale
      (mRS), dichotomized at 3 months into favorable (mRS 0 to 2) and unfavorable (mRS
      3 to 6). RESULTS: One hundred twelve patients exhibited a HMCAS, 55 of 268
      patients treated with IAT and 57 of 249 patients who underwent IVT. Stroke
      severity at baseline and patient age were similar in both groups. Mean time to
      treatment was longer in the IAT group (244+/-63 minutes) than in the IVT group
      (156+/-21 minutes; P=0.0001). However, favorable outcome was more frequent after
      IAT (n=29, 53%) than after IVT (n=13, 23%; P=0.001), and mortality was lower
      after IAT (n=4, 7%) than after IVT (n=13, 23%; P=0.022). After multiple
      regression analysis IAT was associated with a more favorable outcome than IVT
      (P=0.003) but similar mortality (P=0.192). CONCLUSIONS: In this observational
      study intraarterial thrombolysis was more beneficial than IVT in the specific
      group of stroke patients presenting with HMCAS on CT, even though IAT was started
      later. Our results indicate that a randomized trial comparing both thrombolytic
      treatments in patients with middle cerebral artery occlusion is warranted.

PMID- 18096843
TI  - Association of characteristics of blood pressure profiles and stroke outcomes in
      the ECASS-II trial.
AB  - BACKGROUND AND PURPOSE: Certain characteristics of early blood pressure (BP)
      profiles were reported to be independent predictors of long-term outcome in the
      first European Cooperative Acute Stroke Study (ECASS-I) trial. The aim of the
      study was to find out the association of BP profiles with functional outcome,
      mortality, and hemorrhagic complications in the ECASS-II database. METHODS: We
      studied 793 patients with acute ischemic hemispheric stroke in the ECASS-II.
      After randomization, BP was measured every 15 minutes during the first 2 hours,
      then every 30 minutes during the first 8 hours, and thereafter at 1-hour
      intervals up to 24 hours. Individual 0- to 24-hour BP profiles were characterized
      by baseline, maximum, minimum, and mean BP and successive variation of the
      profile. The end points were favorable outcome (modified Rankin Scale score of 0
      or 1) at day 90, all-cause mortality at day 90, and hemorrhagic transformation
      within the first 7 days. RESULTS: High baseline, maximum, mean level, and
      variability of systolic BP profiles were each inversely associated with favorable
      outcome (OR=0.84, 95% CI: 0.74 to 0.94; OR=0.82, 95% CI: 0.73 to 0.91; OR=0.81,
      95% CI: 0.71 to 0.93; OR=0.57, 95% CI: 0.35 to 0.92, respectively) and associated
      with an increased risk of parenchymal hemorrhage within the first 7 days
      (OR=1.27, 95% CI: 1.07 to 1.51; OR=1.49, 95% CI: 1.27 to 1.75; OR=1.52, 95% CI:
      1.23 to 1.87; OR=2.62, 95% CI: 1.40 to 4.87; respectively) in recombinant tissue
      plasminogen activator-treated patients. In placebo-treated patients, high
      maximum, mean level, and successive variation of systolic BP profiles were
      inversely associated with favorable outcome (OR=0.76, 95% CI: 0.66 to 0.86;
      OR=0.76, 95% CI: 0.65 to 0.89; OR=0.41, 95% CI: 0.22 to 0.76; respectively),
      although the association of baseline systolic BP and favorable outcome was not
      significant (OR=0.91, 95% CI: 0.80 to 1.03). No association with hemorrhagic
      transformation was found, even after the adjustment. CONCLUSIONS: The hemorrhagic
      transformation within the first 7 days and favorable outcome were independently
      associated with dynamics of BP within the first 24 hours after an acute ischemic
      stroke in patients treated with thrombolysis, but in placebo-treated patients,
      only with favorable outcome. Continuous BP monitoring is hence important for the
      prognosis and gives implications to optimize BP management, particularly
      regarding a reasonable BP level and stability.

PMID- 18096844
TI  - Subcortical lacunes are associated with executive dysfunction in cognitively
      normal elderly.
AB  - BACKGROUND AND PURPOSE: The relationship between subcortical ischemic vascular
      disease (SIVD) and cognition in normal elderly is unclear, in part because of
      methodological inconsistencies across studies. To clarify this relationship, the
      current study investigated a well characterized cognitively normal elderly sample
      (>or=55 years) with quantitative MRI and psychometrically robust
      neuropsychological measures within a multivariate model. Converging evidence
      suggests that SIVD selectively impairs frontal-executive tasks by disrupting
      frontal-subcortical circuits. We therefore hypothesized that MRI markers of SIVD
      would be selectively associated with worse executive functioning. METHODS: We
      studied 94 participants who were cognitively and functionally normal. Volumetric
      measures of white matter signal hyperintensity (WMH), subcortical lacunes,
      hippocampal volume, and cortical gray matter were obtained to predict performance
      on composite measures of executive functioning and episodic memory. RESULTS:
      Hierarchical regression demonstrated that after controlling for demographic
      variables, MMSE, and total intracranial volume, the total number of subcortical
      lacunes was the only significant predictor, with a greater number of lacunes
      associated with poorer executive performance. Hippocampal volume best predicted
      episodic memory performance. CONCLUSIONS: Results suggest that SIVD in the form
      of silent lacunes corresponds to poorer executive functioning even in otherwise
      normal elderly, which is consistent with the hypothesis that SIVD preferentially
      disrupts frontal-subcortical circuits. The clinical importance of these findings
      is highlighted by the fact that 33% of the normal elderly participants in this
      study had lacunar infarcts.

PMID- 18096845
TI  - Cerebrovascular responses to hypoxia and hypocapnia in Ethiopian high altitude
      dwellers.
AB  - BACKGROUND AND PURPOSE: Cerebrovascular responses to hypoxia and hypocapnia in
      Peruvian altitude dwellers are impaired. This could contribute to the high
      incidence of altitude-related illness in Andeans. Ethiopian high altitude
      dwellers may show a different pattern of adaptation to high altitude. We aimed to
      examine cerebral reactivity to hypoxia and hypocapnia in healthy Ethiopian high
      altitude dwellers. Responses were compared with our previous data from Peruvians.
      METHODS: We studied 9 Ethiopian men at their permanent residence of 3622 m, and
      one day after descent to 794 m. We continuously recorded cerebral blood flow
      velocity (CBFV; transcranial Doppler). End-tidal oxygen (P(ET)o(2)) was decreased
      from 100 mm Hg to 50 mm Hg with end-tidal carbon dioxide (P(ET)co(2)) clamped at
      the subject's resting level. P(ET)co(2) was then manipulated by voluntary hyper-
      and hypoventilation, with P(ET)o(2) clamped at 100 mm Hg (normoxia) and 50 mm Hg
      (hypoxia). RESULTS: During spontaneous breathing, P(ET)co(2) increased after
      descent, from 38.2+/-1.0 mm Hg to 49.8+/-0.6 mm Hg (P<0.001). There was no
      significant response of CBFV to hypoxia at either high (-0.19+/-3.1%) or low
      (1.1+/-2.9%) altitudes. Cerebrovascular reactivity to normoxic hypocapnia at high
      and low altitudes was 3.92+/-0.5%.mm Hg(-1) and 3.09+/-0.4%.mm Hg(-1); reactivity
      to hypoxic hypocapnia was 4.83+/-0.7%.mm Hg(-1) and 2.82+/-0.5%.mm Hg(-1).
      Responses to hypoxic hypocapnia were significantly smaller at low altitude.
      CONCLUSIONS: The cerebral circulation of Ethiopian high altitude dwellers is
      insensitive to hypoxia, unlike Peruvian high altitude dwellers. Cerebrovascular
      responses to P(ET)co(2) were greater in Ethiopians than Peruvians, particularly
      at high altitude. This, coupled with their high P(ET)co(2) levels, would lead to
      high cerebral blood flows, and may be advantageous for altitude living.

PMID- 18096846
TI  - Probing the interior of living cells with fluorescence correlation spectroscopy.
AB  - To a large extent the cellular interior is occupied by two complex fluids, the
      cytoplasm and the nucleoplasm, both of which show a considerable degree of
      macromolecular crowding. While it is easy to imagine that the chromosomal DNA
      provides the nucleoplasm with properties similar to a polymer melt, the material
      properties of the cytoplasm are also affected by the high amount of dissolved
      macromolecules, the cytoskeletal network, and dispersed organelles. By virtue of
      the strongly obstructed random motion, reactions in the cytoplasm and nucleoplasm
      are not comparable to the aqueous conditions commonly used in biochemical
      experiments. To overcome this gap, a thorough understanding of the material
      properties of intracellular fluids, and hence transport properties within the
      cell, is mandatory. Here, we review some recent results on bulk diffusion in
      living cells and some generic consequences that arise from these observations.

PMID- 18096847
TI  - Tungsten, the surprisingly positively acting heavy metal element for prokaryotes.
AB  - The history and changing function of tungsten as the heaviest element in
      biological systems is given. It starts from an inhibitory element/anion,
      especially for the iron molybdenum-cofactor (FeMoCo)-containing enzyme
      nitrogenase involved in dinitrogen fixation, as well as for the many "metal
      binding pterin" (MPT)-, also known as tricyclic pyranopterin- containing classic
      molybdoenzymes, such as the sulfite oxidase and the xanthine dehydrogenase family
      of enzymes. They are generally involved in the transformation of a variety of
      carbon-, nitrogen- and sulfur-containing compounds. But tungstate can serve as a
      potential positively acting element for some enzymes of the dimethyl sulfoxide
      (DMSO) reductase family, especially for CO(2)-reducing formate dehydrogenases
      (FDHs), formylmethanofuran dehydrogenases and acetylene hydratase (catalyzing
      only an addition of water, but no redox reaction). Tungsten even becomes an
      essential element for nearly all enzymes of the aldehyde oxidoreductase (AOR)
      family. Due to the close chemical and physical similarities between molybdate and
      tungstate, the latter was thought to be only unselectively cotransported or
      cometabolized with other tetrahedral anions, such as molybdate and also sulfate.
      However, it has now become clear that it can also be very selectively transported
      compared to molybdate into some prokaryotic cells by two very selective ABC-type
      of transporters that contain a binding protein TupA or WtpA. Both proteins
      exhibit an extremely high affinity for tungstate (K(D) < 1 nM) and can even
      discriminate between tungstate and molybdate. By that process, tungsten finally
      becomes selectively incorporated into the few enzymes noted above.

PMID- 18096848
TI  - Structural factors influencing the efficacy of neuromuscular transmission.
AB  - Neuromuscular junctions (NMJs) in different species share many features of
      structure and function. At the same time, important differences distinguish, for
      example, human NMJs from those in other species. An understanding of the
      biological context of the human NMJ helps in the interpretation of the effects of
      disease on the biophysical properties of neuromuscular transmission. Many NMJs
      consist of a number of spot-like synaptic regions 1-5 microm across. Usually only
      a few multimolecular "quanta" of transmitter are released from each presynaptic
      "bouton" by a single nerve impulse. The total number of quanta released from an
      NMJ is roughly proportional to its total area. For example, human NMJs are about
      10-fold smaller than those in frogs and release about 20 quanta/impulse versus
      100-200 in frog NMJ. Although human NMJs release relatively few quanta, the
      effect of the transmitter is amplified by the high density of voltage-gated
      sodium channels (Na(V)1.4) in the highly folded postsynaptic membrane. A genetic
      influence on NMJ size has recently been discovered in some patients with limb
      girdle myasthenia (LGM). Mutations of the gene encoding Dok-7, an essential
      component of the agrin-muscle-specific kinase pathway that controls postsynaptic
      differentiation at the mammalian NMJ, results in impaired transmission because
      the NMJs are abnormally small and have reduced folding but have a normal local
      density of normal acetylcholine receptors. This condition emphasizes the
      importance of structural features in achieving reliability of neuromuscular
      transmission.

PMID- 18096849
TI  - Cellulases of mesophilic microorganisms: cellulosome and noncellulosome
      producers.
AB  - The cellulolytic activity of mesophilic bacteria and fungi is described, with
      special emphasis on the large extracellular enzyme complex called the
      cellulosome. The cellulosome is composed of a scaffolding protein, which is
      attached to various cellulolytic and hemicellulolytic enzymes, and this complex
      allows the organisms to degrade plant cell walls very efficently. The enzymes
      include a variety of cellulases, hemicellulases, and pectinases that work
      synergistically to degrade complex cell-wall molecules.

PMID- 18096850
TI  - Treatment of myasthenia gravis acute exacerbations with intravenous
      immunoglobulin.
AB  - The results of four randomized controlled trials were examined to assess the
      efficacy of intravenous immunoglobulin (IVIG) for myasthenia gravis (MG) acute
      exacerbations. The first trial compared plasma exchange (PE) and IVIG in 87
      patients. At day 15, the mean change in the Myasthenic Muscular Score (MMS) was
      16.6 (95% CI 11.6-21.6) in the PE group and 15.6 (95% CI 10.9-20.3) in the IVIG
      group (Wilcoxon signed rank test, P = 0.65). The second trial compared IVIG to
      oral methylprednisolone, and 33 patients were included. The mean (SD) sum of the
      two most pathological items of the Quantitative Myasthenia Gravis Score (QMGS) at
      day 0 was 3.9 (1.1) for the IVIG group and 4.2 (0.7) for the methylprednisolone
      group. At day 14, these values were 2.9 (1.4) for the IVIG group and 2.8 (1.1)
      for the methylprednisolone group. The third trial compared IVIG 2 g/kg versus
      placebo for MG worsening. The mean change in QMGS at day 14 was -2.54 in the IVIG
      group and -0.89 in the placebo group (P = 0.047). A significant IVIG treatment
      effect was observed only in patients with more severe disease; the mean
      difference was -0.10 for mild MG (P = 0.914) and -3.39 for moderate to severe MG
      (P = 0.010). The last trial compared IGIV 2 g/kg versus 1 g/kg for MG acute
      exacerbation in 173 patients. The mean MMS change in both groups was similar
      (difference = 3.84; 95% CI -1.03 to 8.71; P = 0.12). In conclusion, IVIG may be
      used as treatment for MG acute exacerbations. IVIG at a dose of 1 g/kg may be
      sufficient.

PMID- 18096851
TI  - Promiscuous anaerobes: new and unconventional metabolism in methanogenic archaea.
AB  - The development of an oxygenated atmosphere on earth resulted in the polarization
      of life into two major groups, those that could live in the presence of oxygen
      and those that could not-the aerobes and the anaerobes. The evolution of aerobes
      from the earliest anaerobic prokaryotes resulted in a variety of metabolic
      adaptations. Many of these adaptations center on the need to sustain oxygen
      sensitive reactions and cofactors to function in the new oxygen-containing
      atmosphere. Still other metabolic pathways that were not sensitive to oxygen also
      diverged. This is likely due to the physical separation of the organisms, based
      on their ability to live in the presence of oxygen, which allowed for the
      independent evolution of the pathways. Through the study of metabolic pathways in
      anaerobes and comparison to the more established pathways from aerobes, insight
      into metabolic evolution can be gained. This, in turn, can allow for extra-
      polation to those metabolic pathways occurring in the Last Universal Common
      Ancestor (LUCA). Some of the unique and uncanonical metabolic pathways that have
      been identified in the archaea with emphasis on the biochemistry of an obligate
      anaerobic methanogen, Methanocaldococcus jannaschii are reviewed.

PMID- 18096852
TI  - Tacrolimus for myasthenia gravis: a clinical study of 212 patients.
AB  - Tacrolimus is a macrolide T cell immunomodulator that is used in myasthenia
      gravis (MG) patients to affect muscle contraction (ryanodine receptor by
      modulating intracellular calcium-release channels and increasing muscular
      strength), glucocorticoid receptors (increasing intracellular concentration of
      steroids and blocking the steroid export mechanism), and an increase in T cell
      apoptosis. In this study, we report the results of low-dose tacrolimus (0.1
      mg/kg/day) treatment in 212 MG patients. There were 110 thymectomized,
      cyclosporine- and prednisone-dependent patients; 68 thymectomized patients who
      started tacrolimus early postoperatively (24 h after operation); and 34 patients
      over 60 years old with nonthymomatous generalized MG or in whom thymectomy was
      contraindicated. The mean follow-up time was 49.3 +/- 18.1 months. Muscular
      strength showed an increase of 23% after 1 month of treatment and 29% at the end
      of the study. The acetylcholine receptor antibodies decreased significantly from
      a mean of 33.5 nmol/L at base line to 7.8 nmol/L at the final visit. In the
      thymectomy group with combined prednisone and tacrolimus stratified by histology
      of the thymus, the mean probability to attain complete stable remission at 5
      years was 80.8% in patients with hyperplasia, 48.1% in thymic involution, and
      9.3% in patients with thymoma. In 4.9% of patients, tacrolimus was withdrawn
      because of major adverse effects. Our results suggest that a low dose of
      tacrolimus is effective for MG and could be included to the armamentarium for
      this autoimmune disease. The present results should be interpreted considering
      the limitations of a retrospective clinical study. Confirmation of these results
      in randomized studies is desirable.

PMID- 18096853
TI  - Methane as fuel for anaerobic microorganisms.
AB  - Methane has long been known to be used as a carbon and energy source by some
      aerobic alpha- and delta-proteobacteria. In these organisms the metabolism of
      methane starts with its oxidation with O(2) to methanol, a reaction catalyzed by
      a monooxygenase and therefore restricted to the aerobic world. Methane has
      recently been shown to also fuel the growth of anaerobic microorganisms. The
      oxidation of methane with sulfate and with nitrate have been reported, but the
      mechanisms of anaerobic methane oxidation still remains elusive. Sulfate
      dependent methane oxidation is catalyzed by methanotrophic archaea, which are
      related to the Methanosarcinales and which grow in close association with sulfate
      reducing delta-proteobacteria. There is evidence that anaerobic methane oxidation
      with sulfate proceeds at least in part via reversed methanogenesis involving the
      nickel enzyme methyl-coenzyme M reductase for methane activation, which under
      standard conditions is an endergonic reaction, and thus inherently slow. Methane
      oxidation coupled to denitrification is mediated by bacteria belonging to a novel
      phylum and does not involve methyl-coenzyme M reductase. The first step in
      methane oxidation is most likely the exergonic formation of 2-methylsuccinate
      from fumarate and methane catalyzed by a glycine-radical enzyme.

PMID- 18096854
TI  - Myasthenia gravis experimentally induced with muscle-specific kinase.
AB  - Here we present the first evidence that muscle-specific kinase (MuSK) antigen can
      cause myasthenia in animals. MuSK is expressed at the postsynaptic membranes of
      neuromuscular junctions (NMJ) and forms complexes with acetylcholine receptors
      (AChR) and rapsyn. MuSK is activated by agrin, which is released from
      motoneurons, and induces AChR clustering and subsequent formation of NMJ in
      embryos. Notably, autoantibodies against MuSK were found in a proportion of
      patients with generalized myasthenia gravis (MG) but without the characteristic
      AChR autoantibodies. However, MuSK autoantibodies had no known pathogenic
      potential, and animals immunized with purified MuSK proteins did not develop MG
      in former studies. In contrast, we have now injected rabbits with MuSK ectodomain
      protein in vivo and evoked a MG-like muscle weakness with a reduction of AChR
      clustering at the NMJ. Our results showed that MuSK is required for maintenance
      of synapses and that interference with that function by MuSK antibodies causes
      myasthenic weakness. In vitro, AChR clustering in myotubes is induced by agrin
      and agrin-independent inducers, which do not activate MuSK. Neither the receptor
      nor the activation mechanisms of AChR clustering induced by agrin-independent
      inducers has been identified with certainty, but MuSK autoantibodies in
      myasthenic animals inhibited both agrin and agrin-independent AChR clustering.
      MuSK plays multiple roles in pre-patterning of the postsynaptic membrane before
      innervation and formation of NMJ in embryos. Some of these mechanisms may also
      participate in the maintenance of mature NMJ. This model system would provide new
      knowledge about the molecular pathogenesis of MG and MuSK functions in mature
      NMJ.

PMID- 18096855
TI  - Substrate arrays for fluorescence-based enzyme fingerprinting and high-throughput
      screening.
AB  - Indirect release of fluorogenic phenols such as umbelliferone was used as a
      chemical principle to prepare fluorogenic substrates for a variety of enzymes in
      which the enzyme-reactive group is separated from the fluorescent reporter group,
      allowing structural and functional diversification. Fluorescent probes were
      obtained for enzymes useful for asymmetric synthesis including aldolase catalytic
      antibodies, transaldolases, alcohol dehydrogenases, lipases, epoxide hydrolases,
      proteases, and Bayer-Villiger monoxygenases. Arrays of structurally related
      substrates were prepared and used to record the activity of enzymes on multiple
      substrates simultaneously in parallel formats such as microtiter plates,
      microarrays, and substrate cocktails, leading to enzyme-specific activity
      patterns. Arrays of nonlabeled substrates were assayed using indirect product
      sensors such as the adrenaline-periodate back-titration assay for 1,2-diols or
      the copper-calcein assay for amino acids. Many of the fluorogenic substrates and
      sensors described here are either commercially available or accessible in one or
      two simple synthetic steps and can be used for high-throughput screening of
      enzyme activities.

PMID- 18096856
TI  - Fluorescent DNA base modifications and substitutes: multiple fluorophore labeling
      and the DETEQ concept.
AB  - There is an increasing need for fluorescent nucleic acid probes that are able to
      sense genetic variations without the application of enzymes. The incorporation of
      organic fluorophores either as DNA base modifications or as DNA base
      substitutions represents a powerful and versatile method for such new fluorescent
      DNA assays. Multiple labeling of oligonucleotides using several adjacent
      chromophore-modified DNA bases yields fluorescence enhancement and modulation
      that are sensitive to single-base mismatches in the complementary
      oligonucleotide. Charge transfer processes that cause fluorescence quenching are
      DNA-base mediated and occur over several base pairs distance. Our "DETEQ" setup,
      consisting of a fluorescence DNA base substitution and the charge acceptor as a
      second modification two base pairs away, allows the homogeneous detection of
      single-base mutations simply by fluorescence readout. This could lead to new DNA
      microarrays which are based on charge transfer processes and can be analyzed by
      commonly used fluorescence readout techniques.

PMID- 18096857
TI  - Screening for domestic violence in public welfare offices: an analysis of case
      manager and client interactions.
AB  - Despite a high prevalence of domestic violence among welfare clients, most
      studies of the implementation of the Family Violence Option (FVO) under welfare
      reform find that women rarely receive domestic violence services in welfare
      offices. This study reviews findings from current research on the factors that
      improve the likelihood that women will reveal their domestic violence experiences
      to service personnel, and uses the guidelines drawn from this review to evaluate
      domestic violence screening practices in welfare offices using 782 transcribed
      interviews between welfare workers and clients from 11 sites in four states. The
      analysis found that only 9.3% of case encounters involved screening for domestic
      violence. Screening rates differed by state, interview type, and length of worker
      employment. Qualitative analysis of the interviews showed that the majority of
      screening by workers was routine or consisted of informing clients of the
      domestic violence policy without asking about abuse. Only 1.2% of the interviews
      incorporated at least two of the procedures that increase the likelihood of
      disclosure among domestic violence survivors, suggesting deeply inadequate
      approaches to screening for abuse within the context of welfare offices, and a
      need for improved training, protocol, and monitoring of FVO implementation.

PMID- 18096858
TI  - Histories of violent victimization among women who reported unwanted sex in
      marriages and intimate relationships: findings from a qualitative study.
AB  - This article summarizes results of semistructured telephone interviews with 41
      women about experiences with various forms of violent victimization. Women who
      reported an incident or incidents of unwanted sex in their intimate partner
      relationships were recruited from a national telephone poll and interviewed about
      other types of victimization, such as childhood maltreatment, unwanted sex by a
      date or acquaintance, and nonsexual violence by a husband or partner. Results
      suggest that women who report unwanted sex by a husband or partner have commonly
      experienced various other forms of abuse in their lives. The author discusses
      implications of the findings for prevention of unwanted sex in intimate
      relationships.

PMID- 18096859
TI  - What we know about intimate partner violence in the Middle East and North Africa.
AB  - Little is known about intimate partner violence in the Middle East and North
      Africa. This review synthesizes and critically evaluates the literature. Of 59
      studies found, only 21 reported data on the prevalence of such violence or on
      beliefs regarding its justification, covering just 9 countries. Spousal abuse is
      pervasive and widely accepted. Victims are of all ages and are more likely to be
      rural and less educated. National data from Egypt and Jordan indicate almost 9 in
      10 ever-married women accept at least one reason for wife beating. Change is
      possible but will require increased research, coalition building, and
      intervention efforts.

PMID- 18096860
TI  - The experience of abused women with their children's law guardians.
AB  - In-depth unstructured interviews are conducted with previously abused divorced
      mothers about their experience with law guardians of their children. Interviews
      are transcribed and their content analyzed using ATLAS.ti software. Nine themes
      clustered in the following three groups emerge: perceived performance of law
      guardians; perceived shortcomings of the system, which provides a context for
      interaction with law guardians; and emotional effects on women. These themes are
      discussed and illustrated, and implications for practice are suggested.

PMID- 18096861
TI  - Getting beyond "what did she do to provoke him?": comments by a retired judge on
      the special issue on child custody and domestic violence.

PMID- 18096862
TI  - Peer sexual harassment: finding voice, changing culture--an intervention strategy
      for adolescent females.
AB  - This exploratory intervention study examines the effectiveness of a single-sex
      women's studies course in reducing sexual harassment in an at-risk high school.
      It was hypothesized that the young women's loci of control would become more
      internal as a result of the course and participants would feel they had more
      control over their lives. Findings indicate that participants' knowledge of
      sexual harassment gained from the intervention had been retained and reports of
      sexual harassment increased. Administrative referrals for sexual harassment
      within the school were reduced by one third during the semester following the
      intervention. Participants' perceptions of their levels of internality increased
      over time.

PMID- 18096863
TI  - Association of insurance with cancer care utilization and outcomes.
AB  - Advances in the prevention, early detection, and treatment of cancer have
      resulted in an almost 14% decrease in the death rates from all cancers combined
      from 1991 to 2004 in the overall US population, with remarkable declines in
      mortality for the top 3 causes of cancer death in men (lung, colorectal, and
      prostate cancer) and 2 of the top 3 cancers in women (breast and colorectal
      cancer). However, not all segments of the population have benefited equally from
      this progress, and evidence suggests that some of these differences are related
      to lack of access to health care. Lack of adequate health insurance appears to be
      a critical barrier to receipt of appropriate health care services. This article
      provides an overview of systems of health insurance in the United States,
      demographic and socioeconomic characteristics associated with health insurance
      coverage, and economic burdens related to health care among individuals and
      families. This article also presents data on the association between health
      insurance status and screening, stage at diagnosis, and survival for breast and
      colorectal cancer based on analyses of the National Health Interview Survey and
      the National Cancer Data Base. Although this article focuses on associations
      between health insurance and cancer care utilization and outcomes, it is
      important to recognize that barriers to receipt of optimal cancer care are
      complex and involve patient-level, provider, and health system factors. Evidence
      presented in this paper suggests that addressing insurance and cost-related
      barriers to care is a critical component of efforts to ensure that all Americans
      are able to share in the progress that can be achieved by access to high-quality
      cancer prevention, early detection, and treatment services.

PMID- 18096864
TI  - Editorial.

PMID- 18096865
TI  - Expanding role of the medical oncologist in the management of head and neck
      cancer.
AB  - The multidisciplinary approach to treating squamous cell carcinoma of the head
      and neck is complex and evolving. This article aims to review some recent
      developments in squamous cell carcinoma of the head and neck, in particular the
      expanding role of chemotherapy in its management. Surgery and radiotherapy have
      remained the mainstay of therapy. Chemotherapy is increasingly being incorporated
      into the treatment of squamous cell carcinoma of the head and neck. Previously,
      radiotherapy following surgery was the standard approach to the treatment of
      locoregionally advanced resectable disease. Data from randomized trials have
      confirmed the benefits of concurrent chemoradiotherapy in the adjuvant setting.
      Chemoradiotherapy is also the recommended approach for unresectable disease.
      Induction chemotherapy has been useful in resectable disease where organ
      preservation is desirable, but this approach was inferior for the goal of larynx
      preservation, while leading to similar survival when compared with concomitant
      chemoradiotherapy. There is recent evidence that taxanes added to induction
      chemotherapy with cisplatin and fluorouracil result in improved survival
      outcomes. Novel targeted agents, such as epidermal growth factor receptor
      antagonists, are showing promise in the treatment of patients with both
      locoregionally advanced and recurrent/metastatic squamous cell carcinoma of the
      head and neck.

PMID- 18096866
TI  - Utilizing the tumor-node-metastasis staging for prostate cancer: the sixth
      edition, 2002.
AB  - The Sixth Edition of the tumor-node-metastasis staging system for prostate cancer
      attempts to provide a helpful staging paradigm for clinicians. Accurate staging
      is critical not only for managing individual patients, but also for ascertaining
      trends in disease pattern in a large population of patients with prostate cancer.
      Several modifications have been made in an attempt to improve the cohesiveness
      and uniformity of patient evaluation and to aid in future meaningful clinical
      research. As data are accumulated and analysis continues, ongoing critical
      evaluation of this staging system will undoubtedly incorporate new evidence-based
      factors and bring about future refinements to prostate cancer staging.

PMID- 18096868
TI  - Nickel alterations of TLR2-dependent chemokine profiles in lung fibroblasts are
      mediated by COX-2.
AB  - Particulate matter air pollution (PM) has been linked with chronic respiratory
      diseases. Real-life exposures are likely to involve a mixture of chemical and
      microbial stimuli, yet little attention has been paid to the potential
      interactions between PM components (e.g., Ni) and microbial agents on the
      development of inflammatory-like conditions in the lung. Using the Toll-like
      receptor (TLR)-2 agonist MALP-2 as a lipopeptide relevant to microbial
      colonization, we hypothesized that nickel sensitizes human lung fibroblasts (HLF)
      for microbial-driven chemokine release through modulation of TLR signaling
      pathways. NiSO(4) (200 muM) synergistically enhanced CXCL8, yet antagonized
      CXCL10 mRNA expression and protein release from HLF in response to MALP-2. RT(2)
      PCR pathway-focused array results indicated that NiSO(4) exposure did not alter
      the expression of TLRs or their downstream signaling mediators, yet significantly
      increased the expression of cyclooxygenase 2 (COX-2). Moreover, when NiSO(4) was
      given in combination with MALP-2, there was an amplified induction of COX-2 mRNA
      and protein along with its metabolic product, PGE2, in HLF. The COX-2 inhibitor,
      NS-398, attenuated NiSO(4) and MALP-2-induced PGE2 and CXCL8 release and
      partially reversed the NiSO(4)-dependent inhibition of MALP-2-induced CXCL10
      release from HLF. These data indicate that NiSO(4) alters the pattern of TLR-2
      dependent chemokine release from HLF via a COX-2-mediated pathway. The
      quantitative and qualitative effects of NiSO(4) on microbial-driven chemokine
      release from HLF shed new light on how PM-derived metals can exacerbate
      respiratory diseases.

PMID- 18096867
TI  - Haemophilus influenzae lysate induces aspects of the chronic obstructive
      pulmonary disease phenotype.
AB  - Nontypeable Haemophilus influenzae (NTHi) commonly colonizes the lower airways of
      patients with chronic obstructive pulmonary disease (COPD). Whether it
      contributes to COPD progression is unknown. Here, we determined which aspects of
      the COPD phenotype can be induced by repetitive exposure to NTHi products. Mice
      were exposed weekly to an aerosolized NTHi lysate, and inflammation was evaluated
      by measurement of cells and cytokines in bronchoalveolar lavage fluid (BALF) and
      immunohistochemical staining; structural changes were evaluated histochemically
      by periodic acid fluorescent Schiff's reagent, Masson's trichrome, and
      Picrosirius red staining; mucin gene expression was measured by quantitative RT
      PCR; and the role of TNF-alpha was examined by transgenic airway overexpression
      and use of an inhibitory antibody. NTHi lysate induced rapid activation of NF
      kappaB in airway cells and increases of inflammatory cytokines and neutrophils in
      BALF. Repetitive exposure induced infiltration of macrophages, CD8+ T cells, and
      B cells around airways and blood vessels, and collagen deposition in airway and
      alveolar walls, but airway mucin staining and gel-forming mucin transcripts were
      not increased. Transgenic overexpression of TNF-alpha caused BALF neutrophilia
      and inflammatory cell infiltration around airways, but not fibrosis, and TNF
      alpha neutralization did not reduce BALF neutrophilia in response to NTHi lysate.
      In conclusion, NTHi products elicit airway inflammation in mice with a cellular
      and cytokine profile similar to that in COPD, and cause airway wall fibrosis but
      not mucous metaplasia. TNF-alpha is neither required for inflammatory cell
      recruitment nor sufficient for airway fibrosis. Colonization by NTHi may
      contribute to the pathogenesis of small airways disease in patients with COPD.

PMID- 18096869
TI  - STAT3 regulates ABCA3 expression and influences lamellar body formation in
      alveolar type II cells.
AB  - ATP-Binding Cassette A3 (ABCA3) is a lamellar body associated lipid transport
      protein required for normal synthesis and storage of pulmonary surfactant in type
      II cells in the alveoli. In this study, we demonstrate that STAT3, activated by
      IL-6, regulates ABCA3 expression in vivo and in vitro. ABCA3 mRNA and
      immunostaining were decreased in adult mouse lungs in which STAT3 was deleted
      from the respiratory epithelium (Stat3(Delta/Delta) mice). Consistent with the
      role of STAT3, intratracheal IL-6 induced ABCA3 expression in vivo. Decreased
      ABCA3 and abnormalities in the formation of lamellar bodies, the intracellular
      site of surfactant lipid storage, were observed in Stat3(Delta/Delta) mice.
      Expression of SREBP1a and 1c, SCAP, ABCA3, and AKT mRNAs was inhibited by
      deletion of Stat3 in type II cells isolated from Stat3(Delta/Delta) mice. The
      activities of PI3K and AKT were required for normal Abca3 gene expression in
      vitro. AKT activation induced SREBP expression and increased the activity of the
      Abca3 promoter in vitro, consistent with the role of STAT3 signaling, at least in
      part via SREBP, in the regulation of ABCA3. ABCA3 expression is regulated by IL-6
      in a pathway that includes STAT3, PI3K, AKT, SCAP, and SREBP. Activation of STAT3
      after exposure to IL-6 enhances ABCA3 expression, which, in turn, influences
      pulmonary surfactant homeostasis.

PMID- 18096870
TI  - Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice.
AB  - Interleukin-6 (IL-6) is known to be involved in the pathogenesis of various
      inflammatory diseases, but its role in bleomycin (BLM)-induced lung injury and
      subsequent fibrotic changes remains to be determined. We evaluated the role of IL
      6 in the lung inflammatory changes induced by BLM using wild-type (WT) and IL-6
      deficient (IL-6(-/-)) mice. The mice were treated intratracheally with 1 mg/kg
      BLM and killed 2, 7, or 21 days later. Lung Inflammation in the acute phase (Days
      2 and 7) was assessed by differential cell counts in bronchoalveolar lavage (BAL)
      fluid and cytokine levels in the lung. Lung fibrotic changes were evaluated on
      Day 21 by histopathology and collagen assay. On Day 2, BLM administration induced
      significant increases in the numbers of total cells, macrophages, and neutrophils
      in BAL fluid, which were attenuated in IL-6(-/-) mice (P < 0.05). Lung pathology
      also showed inflammatory cell accumulation, which was attenuated in the IL-6(-/-)
      mice compared with WT mice. In WT mice, elevated levels of TGF-beta(1) and CCL3
      were observed 2 and 7 days after BLM challenge, respectively. On Day 7, BLM
      induced inflammatory cell accumulation did not differ between the genotypes. Lung
      pathology 21 days after BLM challenge revealed significant fibrotic changes with
      increased collagen content, which was attenuated in IL-6(-/-) mice. Although the
      TGF-beta(1) level in the lung did not differ between the genotypes on Day 21,
      CCL3 was significantly lower in IL-6(-/-) mice. These results indicate that IL-6
      may play an important role in the pathogenesis of BLM-induced lung injury and
      subsequent fibrotic changes.

PMID- 18096871
TI  - Moraxella-dependent alpha 1-antichymotrypsin neutralization: a unique virulence
      mechanism.
AB  - The acute phase reactant and protease inhibitor alpha(1)-antichymotrypsin is
      considered to play a protective role in the airways, but whether it interacts
      with respiratory bacteria is not known. We analyzed whether the common
      respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella
      catarrhalis, and other bacterial species interact with antichymotrypsin. M.
      catarrhalis was the only species that bound antichymotrypsin among 25 bacterial
      species tested by flow cytometry and direct binding assay. We compared a series
      of clinical isolates in addition to wild-type and ubiquitous surface protein
      deficient Moraxella to study the nature of antichymotrypsin binding by the
      bacteria. Experiments with Moraxella mutants revealed that ubiquitous surface
      proteins A1 and A2 were responsible for the interaction, and using recombinant
      fragments, a consensus sequence within ubiquitous surface proteins A1 and A2 was
      defined. Binding of iodine-labeled antichymotrypsin was dose dependent and strong
      (dissociation constant [K(d)] 24.9-44.8 nM). Moreover, a chymotrypsin activity
      assay showed that antichymotrypsin, when bound to the bacterial surface, was
      neutralized. Moraxella antichymotrypsin neutralization is a novel microbial
      virulence mechanism that may induce excessive inflammation resulting in more
      exposed extracellular matrix that is beneficial for bacterial colonization.

PMID- 18096872
TI  - Chronic exposure to beta-blockers attenuates inflammation and mucin content in a
      murine asthma model.
AB  - Single-dose administration of beta-adrenoceptor agonists produces bronchodilation
      and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for
      the acute relief of asthma. However, chronic repetitive administration of beta
      adrenoceptor agonists may increase AHR, airway inflammation, and risk of death.
      Based upon the paradigm shift that occurred with the use of beta-blockers in
      congestive heart failure, we previously determined that chronic administration of
      beta-blockers decreased AHR in a murine model of asthma. To elucidate the
      mechanisms for the beneficial effects of beta-blockers, we examined the effects
      of chronic administration of several beta-adrenoceptor ligands in a murine model
      of allergic asthma. Administration of beta-blockers resulted in a reduction in
      total cell counts, eosinophils, and the cytokines IL-13, IL-10, IL-5, and TGF
      beta1 in bronchoalveolar lavage, and attenuated epithelial mucin content and
      morphologic changes. The differences in mucin content also occurred if the beta
      blockers were administered only during the ovalbumin challenge phase, but
      administration of beta-blockers for 7 days was not as effective as administration
      for 28 days. These results indicate that in a murine model of asthma, chronic
      administration of beta-blockers reduces inflammation and mucous metaplasia,
      cardinal features of asthma that may contribute to airflow obstruction and AHR.
      Similar to heart failure, our results provide a second disease model in which
      beta-blockers producing an acutely detrimental effect may provide a
      therapeutically beneficial effect with chronic administration.

PMID- 18096873
TI  - Sequential exposure to carbon nanotubes and bacteria enhances pulmonary
      inflammation and infectivity.
AB  - Carbon nanotubes (CNT), with their applications in industry and medicine, may
      lead to new risks to human health. CNT induce a robust pulmonary inflammation and
      oxidative stress in rodents. Realistic exposures to CNT may occur in conjunction
      with other pathogenic impacts (microbial infections) and trigger enhanced
      responses. We evaluated interactions between pharyngeal aspiration of single
      walled CNT (SWCNT) and bacterial pulmonary infection of C57BL/6 mice with
      Listeria monocytogenes (LM). Mice were given SWCNT (0, 10, and 40 mug/mouse) and
      3 days later were exposed to LM (10(3) bacteria/mouse). Sequential exposure to
      SWCNT/LM amplified lung inflammation and collagen formation. Despite this robust
      inflammatory response, SWCNT pre-exposure significantly decreased the pulmonary
      clearance of LM-exposed mice measured 3 to 7 days after microbial infection
      versus PBS/LM-treated mice. Decreased bacterial clearance in SWCNT-pre-exposed
      mice was associated with decreased phagocytosis of bacteria by macrophages and a
      decrease in nitric oxide production by these phagocytes. Pre-incubation of naive
      alveolar macrophages with SWCNT in vitro also resulted in decreased nitric oxide
      generation and suppressed phagocytizing activity toward LM. Failure of SWCNT
      exposed mice to clear LM led to a continued elevation in nearly all major
      chemokines and acute phase cytokines into the later course of infection. In
      SWCNT/LM-exposed mice, bronchoalveolar lavage neutrophils, alveolar macrophages,
      and lymphocytes, as well as lactate dehydrogenase level, were increased compared
      with mice exposed to SWCNT or LM alone. In conclusion, enhanced acute
      inflammation and pulmonary injury with delayed bacterial clearance after SWCNT
      exposure may lead to increased susceptibility to lung infection in exposed
      populations.

PMID- 18096874
TI  - Alveolar dynamics during respiration: are the pores of Kohn a pathway to
      recruitment?
AB  - The change in alveolar size and number during the full breathing cycle in mammals
      remains unanswered, yet these descriptors are fundamental for understanding
      alveolar-based diseases and for improving ventilator management. Genetic and
      environmental mouse models are used increasingly to evaluate the evolution of
      disease in the peripheral lung; however, little is known regarding alveolar
      structure and function in the fresh, intact lung. Therefore, we have developed an
      optical confocal process to evaluate alveolar dynamics in the fresh intact mouse
      lung and as an initial experiment, have evaluated mouse alveolar dynamics during
      a single respiratory cycle immediately after passive lung deflation. We observe
      that alveoli become smaller and more numerous at the end of inspiration, and
      propose that this is direct evidence for alveolar recruitment in the mouse lung.
      The findings reported support a new hypothesis that requires recruitable
      secondary (daughter) alveoli to inflate via primary (mother) alveoli rather than
      from a conducting airway.

PMID- 18096875
TI  - HGF increases cisplatin resistance via down-regulation of AIF in lung cancer
      cells.
AB  - Our previous study had shown that advanced stages of lung adenocarcinomas (ADC)
      was frequently associated with overexpression of hepatocyte growth factor (HGF),
      which has multipotent and anti-apoptotic activities. In this study, we examined
      the effect of HGF on gene expression of apoptosis-inducing factor (AIF) and
      cisplatin sensitivity in lung ADC cells. Expression of AIF was determined by
      immunocytochemistry and confocal immunofluorescence microscopy. Our data show
      that addition of HGF suppressed AIF expression and increased cisplatin
      resistance. The effect could be through HGF receptor and its downstream effector,
      focal adhesion kinase (FAK). Interestingly, knockout of FAK gene increased AIF
      expression and drug sensitivity. Re-introduction of FAK gene, on the other hand,
      restored drug resistance. These results suggested that HGF might induce cisplatin
      resistance via c-Met to activate FAK and down-regulate AIF expression.

PMID- 18096876
TI  - Faculty development to support curriculum change and ensure the future vitality
      of dental education.
AB  - For meaningful curriculum change to occur in dental schools, faculty must go
      through a process of new skills development that will prepare them to teach
      differently and to assess students differently than they have before. Curriculum
      change and the faculty development process must have the support of the dental
      school's leadership and become a core value of the school's culture.

PMID- 18096877
TI  - Does faculty development enhance teaching effectiveness?
AB  - Academic dentists and members of the practice community have been hearing, for
      more than a decade, that our educational system is in trouble and that the
      profession has lost its vision and may be wavering in the achievement of its
      goals. A core of consistently recommended reforms has framed the discussion of
      future directions for dental education, but as yet, most schools report little
      movement toward implementation of these reforms in spite of persistent advocacy.
      Provision of faculty development related to teaching and assessment strategies is
      widely perceived to be the essential ingredient in efforts to introduce new
      curricular approaches and modify the educational environment in academic
      dentistry. Analyses of the outcomes of efforts to revise health professions
      curricula have identified the availability and effectiveness of faculty
      development as a predictor of the success or failure of reform initiatives. This
      article will address faculty development for purposes of enhancing teaching
      effectiveness and preparing instructors for potential new roles associated with
      curriculum changes. Its overall purpose is to provide information and insights
      about faculty development that may be useful to dental schools in designing
      professional growth opportunities for their faculty. Seven questions are
      addressed: 1) What is faculty development? 2) How is faculty development
      accomplished? 3) Why is faculty development particularly important in dental
      education? 4) What happens when faculty development does not accompany
      educational reform? 5) Why are teaching attitudes and behaviors so difficult to
      change? 6) What outcomes can be expected from faculty development? and 7) What
      does the available evidence tell us about the design of faculty development
      programs? Evidence from systematic reviews pertaining to the teaching of evidence
      based dentistry, strategies for continuing professional education, and the Best
      Evidence in Medical Education review of faculty development outcomes are
      presented to answer this question: does faculty development enhance teaching
      effectiveness? Characteristics consistently associated with effective faculty
      development are described.

PMID- 18096878
TI  - Routine HIV testing in dental practice: can we cross the Rubicon?
AB  - The latest Centers for Disease Control and Prevention (CDC) guidelines recommend
      routine HIV screening for a large segment of the population, given that the
      individual understands that an HIV test will be performed unless he or she
      declines testing (opt-out testing). The CDC recommendation calls for the
      elimination of formalized requirements for written consent and pretest counseling
      to encourage more Americans to voluntarily accept testing. Knowledge of HIV
      infection can increase early access to care and treatment and reduce further
      transmission. A rapid non-invasive test for HIV infection (OraQuick Advance) from
      oral fluid has recently become available. It offers two distinct advantages: 1)
      results are available within twenty minutes, thereby eliminating a long waiting
      period; and 2) it has high sensitivity and specificity comparable to blood
      testing. A preliminary positive test result must be confirmed with a Western Blot
      by an outside laboratory or physician. Important ethical and legal issues must be
      resolved before the successful implementation of HIV testing in the dental
      setting. An educational emphasis on broader coverage of HIV testing is also
      needed within the dental school curriculum. The integration of HIV testing into
      dental practice is discussed as well. A policy of screening patients in dental
      offices will contribute to a major advance in public health.

PMID- 18096879
TI  - Perceptions about conflicts of interest: an Ontario survey of dentists' opinions.
AB  - The purpose of this study was to explore the opinions that general dental
      practitioners in Ontario have regarding various situations that may be perceived
      as a conflict of interest. Standard quantitative analyses were employed to assess
      the association of attitudes and opinions concerning conflict of interest with
      gender, length of practice, and prior interpersonal communication, ethics, and
      religious training through a survey of general practice dentists in Ontario.
      Positive associations were found between the recognition of conflicts of interest
      and the number of years of dental practice, interpersonal communication training,
      and the reading of ethics-related articles in journals. Opinions vary on what is
      and is not a conflict of interest. Dental education has shaped a better
      understanding of these issues; however, for many dentists, previous education has
      not been totally adequate to guide them through conflict of interest situations.
      Age and mode and length of practice appear to have a direct effect on awareness
      of conflict of interest issues. Dentists need specific instruction and clearer
      direction regarding conflict of interest issues, so that they can better manage
      situations deemed to be conflicting and thereby earn and maintain patient trust
      in the profession.

PMID- 18096880
TI  - Changes in orthodontic care patterns in a predoctoral children's dentistry
      clinic.
AB  - The purpose of this study was to evaluate the changes in orthodontic care
      patterns over a sixteen-year period in a university clinical setting. The average
      numbers of students, clinical procedures, and orthodontic appliances were
      examined from the time period 1988-2003. Appliance number and type were evaluated
      as a function of increased predoctoral and postdoctoral class sizes, student to
      faculty ratios, and decreased operating budgets for faculty recruitment. For the
      period 1988-98, the insertion of orthodontic appliances by dental students
      remained constant. A permanent increase in the predoctoral class size occurred in
      1996 without an increase in faculty support, contributing to a decline in
      appliance insertions by students from 1999 to 2003. This time period also saw
      major increases in the postdoctoral class size and a reorganization of the
      clinical facility that then began to require the pairing of dental students to
      provide comprehensive care, thus decreasing their clinical exposure to the care
      of children. The overall clinical experience at the predoctoral level in
      orthodontic procedures declined, which resulted in a change in clinical
      requirements and new methods to ensure clinical competency.

PMID- 18096881
TI  - A patient-instructor program to promote dental students' communication skills
      with diverse patients.
AB  - This article describes the design and evaluation of a patient-instructor (PI)
      program that was developed to teach and assess dental student communication
      skills with patients, with an emphasis on cross-cultural patient encounters. The
      PIs were individuals from the community trained to portray specific simulated
      patients. One hundred eighteen dental students (three graduating classes)
      completed two half-day rotations that occurred in the junior year; seventy-nine
      of those students (two graduating classes) also completed a third rotation that
      occurred in the senior year. On each rotation, students worked with several
      simulated patients in mock clinic appointments. PIs used a standardized rating
      scale and case-specific content checklists to assess students' ability to elicit
      and provide essential information. Across counterbalanced cases, students
      improved as they progressed through encounters. Rate of improvement varied by
      rotation, but students improved most during their first rotation. Overall
      performance was best on the final rotation. Qualitative review of content
      checklist items indicated areas of strengths and weaknesses in communication
      regarding medical, dental, psychosocial, and cultural content. Results can direct
      curriculum changes to improve communication skills. Future research should
      address the effects of the PI program on students' diversity-related attitudes
      and behaviors.

PMID- 18096882
TI  - PBL Core Skills Faculty Development Workshop 3: understanding PBL process
      assessment and feedback via scenario-based discussions, observation, and role
      play.
AB  - Tutorial assessment in PBL is thought to be a valid assessment approach and is
      believed to exert a positive impact on the learning process. Reports, however,
      have demonstrated that assessment by the facilitator can be unreliable. Training
      of faculty to conduct this type of assessment has tended to be lacking and is a
      likely contributor to this inconsistency. This report describes the final in a
      series of foundation-building faculty development workshops focused on the
      instructional methodology of PBL. The PBL Assessment and Feedback workshop
      reported here introduced the theory and practice of conducting process-based
      assessment accompanied by formative feedback. Scenario-based discussions, mock
      group demonstration, role-modeling, and role-play were utilized as adult learning
      appropriate strategies to familiarize participants with process-based assessment
      and feedback. Evaluation of the workshop by participants provided evidence that
      the majority of participants were satisfied with the methods and content of the
      workshop. Suggestions for additional training in these assessment methods
      included additional examples, practice, workshops, or observation and mentoring.

PMID- 18096883
TI  - Assessment of faculty perception of content validity of PerioSim, a haptic-3D
      virtual reality dental training simulator.
AB  - Haptic technology (sense of touch) along with 3D-virtual reality (VR) graphics,
      creating lifelike training simulations, was used to develop a dental training
      simulator system (PerioSim). This preliminary study was designed to evaluate
      whether faculty considered PerioSim realistic and useful for training and
      evaluating basic procedural skills of students. The haptic device employed was a
      PHANToM and the simulator a Dell Xeon 530 workstation with 3D, VR oral models and
      instruments viewed on a stereoscopic monitor. An onscreen VR periodontal probe or
      explorer was manipulated by operating the PHANToM for sensing lifelike contact
      and interactions with the teeth and gingiva. Thirty experienced clinical dental
      and dental hygiene faculty judged the realism of the system. A PowerPoint
      presentation on one screen provided instructions for the simulator use with the
      3D, VR simulator on a second stereoscopic monitor viewed with 3D goggles.
      Faculty/practitioners found the images very realistic for teeth and instruments,
      but less so for gingiva. Tactile sensation was realistic for teeth but not so for
      gingiva. The onscreen instructions were very useful with high potential for
      teaching. Faculty members anticipated incorporating this device into teaching and
      were enthusiastic about its potential for evaluating students' basic procedural
      skills. This study suggests that the preliminary "evidence-of-concept" was
      successful and PerioSim may aid students in developing necessary dental tactile
      skills.

PMID- 18096884
TI  - How dentists account for social responsibility: economic imperatives and
      professional obligations.
AB  - This study explores how dentists explain the concept of social responsibility and
      its relationship to issues affecting access to oral health care by vulnerable
      segments of the population. Analysis of open-ended interviews with thirty-four
      dentists, including dental educators, and administrators and officials of dental
      public health programs in Canada and the United States revealed that four main
      themes-economics, professionalism, individual choice, and politics-influenced the
      respondents' sense of social responsibility in dentistry. There was a belief that
      social responsibility in dentistry is dominated by economic imperatives that
      impact negatively on the policies and practices directing access to care. Yet,
      despite the highly critical stance on dentistry as a business, there was
      practical recognition of the economic realities of dental practice. Nevertheless,
      those who focused on social responsibility as a professional obligation
      highlighted the privileges of self-governance along with the accompanying duty to
      serve the welfare of everyone and not just those who are socioeconomically
      advantaged.

PMID- 18096885
TI  - Personality types of Chinese dental school applicants.
AB  - This his article reports the findings of a study conducted to investigate the
      personality types of Chinese dental school applicants. The Chinese version of the
      Myers-Briggs Type Indicator (MBTI) (Form G) was used to assess the personality
      styles of 332 dental school applicants from the mainland of China. The results of
      the MBTI for Chinese dental school applicants were compared with a previous study
      of applicants from the U.K. A higher percentage of this group of Chinese
      applicants scored higher for Introversion (I) than Extroversion (E); both Chinese
      and English applicants preferred Judging (J) to Perceiving (P). The dominant
      personality types in Chinese applicants were ISTJ, ESTJ, and ISFP. The findings
      suggest that the personality types of Chinese dental students may be somewhat
      different from the personality profiles exhibited by dental students from other
      nations. The findings may be of value to individuals who desire to investigate
      personality type differences among dental students with different cultural
      backgrounds.

PMID- 18096887
TI  - Is artificial fluoride absorbed to the same extent as natural fluoride?

PMID- 18096889
TI  - Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy.
AB  - The development of oral squamous cell carcinoma (OSCC) is a multistep process
      requiring the accumulation of multiple genetic alterations, influenced by a
      patient's genetic predisposition as well as by environmental influences,
      including tobacco, alcohol, chronic inflammation, and viral infection.
      Tumorigenic genetic alterations consist of two major types: tumor suppressor
      genes, which promote tumor development when inactivated; and oncogenes, which
      promote tumor development when activated. Tumor suppressor genes can be
      inactivated through genetic events such as mutation, loss of heterozygosity, or
      deletion, or by epigenetic modifications such as DNA methylation or chromatin
      remodeling. Oncogenes can be activated through overexpression due to gene
      amplification, increased transcription, or changes in structure due to mutations
      that lead to increased transforming activity. This review focuses on the
      molecular mechanisms of oral carcinogenesis and the use of biologic therapy to
      specifically target molecules altered in OSCC. The rapid progress that has been
      made in our understanding of the molecular alterations contributing to the
      development of OSCC is leading to improvements in the early diagnosis of tumors
      and the refinement of biologic treatments individualized to the specific
      characteristics of a patient's tumor.

PMID- 18096888
TI  - Sphingomyelin degradation is a key factor in dentin and bone mineralization:
      lessons from the fro/fro mouse. The chemistry and histochemistry of dentin
      lipids.

PMID- 18096890
TI  - PDGF up-regulates CSF-1 gene transcription in ameloblast-like cells.
AB  - Macrophage colony-stimulating factor (CSF-1) is a key regulatory cytokine for
      amelogenesis, and ameloblasts synthesize CSF-1. We hypothesized that PDGF
      stimulates DNA synthesis and regulates CSF-1 in these cells. We determined the
      effect of PDGF on CSF-1 expression using MEOE-3M ameloblasts as a model. By RT
      PCR, MEOE-3M expressed PDGFRs and PDGF A- and B-chain mRNAs. PDGF-BB increased
      DNA synthesis and up-regulated CSF-1 mRNA and protein in MEOE-3M. Cells
      transfected with CSF-1 promoter deletion constructs were analyzed. A PDGF
      responsive region between -1.7 and -0.795 kb, containing a consensus Pea3 binding
      motif, was identified. Electrophoretic mobility shift assay (EMSA) showed that
      PDGF-BB stimulated protein binding to this motif that was inhibited in the
      presence of anti-Pea3 antibody. Analysis of these data provides the first
      evidence that PDGF-BB is a mitogen for MEOE-3M and increases CSF-1 protein
      levels, predominantly by transcription. Elucidation of the cellular pathways that
      control CSF-1 expression may provide novel strategies for the regulation of
      enamel matrix formation.

PMID- 18096891
TI  - Effects of fluoride on the interactions between amelogenin and apatite crystals.
AB  - Fluorosed enamel is more porous and less mineralized, possibly related to altered
      amelogenin-modulated crystal growth. The purpose of this study was to examine the
      role of fluoride in interactions between amelogenin and apatite crystals.
      Recombinant human amelogenin (rh174) was bound to carbonated hydroxyapatite
      containing various amounts of fluoride, and analyzed by protein assay, SDS PAGE,
      and AFM. Interactions between rh174 and fluoride were assayed by isothermal
      titration calorimetry (ITC). The initial binding rate of rh174, as well as total
      amount of rh174 bound to fluoride-containing carbonated hydroxyapatite, was
      greater than that in the control carbonated hydroxyapatite. Fluoride in solution
      at physiologic (5.3 micromolar, or 0.1 ppm) concentrations showed no significant
      effect on binding, but higher fluoride levels significantly decreased protein
      binding. ITC showed no interactions between fluoride and rh174. These results
      suggest that fluoride incorporation into the crystal lattice alters the crystal
      surface to enhance amelogenin binding, with no direct interactions between
      fluoride and amelogenin.

PMID- 18096893
TI  - Butyric acid induces apoptosis in inflamed fibroblasts.
AB  - Butyric acid, an extracellular metabolite from periodontopathic bacteria, induces
      apoptosis in murine and human T- and B-cells, whereas intact gingival fibroblasts
      isolated from healthy humans are resistant to butyric-acid-induced apoptosis. We
      examined the susceptibility of inflamed gingival fibroblasts isolated from adult
      persons with periodontitis to butyric-acid-induced apoptosis. Butyric acid
      significantly suppressed the viability of inflamed gingival fibroblasts and
      induced apoptosis in a dose-dependent manner. The incubation of inflamed gingival
      fibroblasts with butyric acid induced DNA fragmentation and apoptotic changes
      such as chromatin condensation, hypodiploid nuclei, and mitochondrial injury.
      Furthermore, butyric-acid-induced apoptosis in inflamed gingival fibroblasts was
      reduced by caspase-3/7, -6, -8, and -9 inhibitors. Thus, inflamed gingival
      fibroblasts from adult persons with periodontitis appear to be highly susceptible
      to mitochondria- and caspase-dependent apoptosis induced by butyric acid,
      compared with healthy gingival fibroblasts.

PMID- 18096892
TI  - Phenotypic analysis of Dlx5 overexpression in post-natal bone.
AB  - Dlx5 plays an important role in the embryonic development of mineralized tissues.
      We hypothesized that Dlx5 also functions in regulating post-natal bone formation
      in mice. To prove this hypothesis, we infected 5-day-old bone sialoprotein
      (BSP)/avian retroviral receptor gene (TVA) transgenic mice with replication
      competent retroviral vectors expressing wild-type Dlx5 (RCAS-Dlx5WT) and mutated
      Dlx5 at arginine (R) 31 of its homeodomain (RCAS-Dlx5RH). Immunohistochemistry
      indicated that RCAS-Dlx5WT increased BSP and osteopontin (OPN) expression,
      whereas it decreased that of osteocalcin (OC). RCAS-Dlx5RH mediated opposite
      effects. Semi-quantitative RT-PCR confirmed these results. Ex vivo overexpression
      of RCAS-Dlx5WT in BSP/TVA calvarial cells promoted, whereas that of RCAS-Dlx5RH
      inhibited, mineralized nodule formation as compared with that in control cells.
      Our results suggest that Dlx5 promotes expression of early markers of osteogenic
      differentiation and increases mineralization post-natally.

PMID- 18096895
TI  - The effects of social class and dental attendance on oral health.
AB  - The relationship between socio-economic status (SES) and oral health is well
      established. We investigated whether the association between SES and the number
      of sound teeth in adults is explained by dental attendance patterns, in turn
      determined by the effect of SES on barriers to dental attendance. Data on 3817
      participants from the 1998 Adult Dental Health Survey in the UK were analyzed.
      Using structural equation modeling, we found a model with 4 factors (aging, SES,
      attendance-profile, and barriers-to-dental-attendance) providing an adequate fit
      to the covariance matrix of the 9 covariates. The final model suggests that the
      association between SES and the number of sound teeth in adults in the UK is
      partially explained by the pathway [SES --> barriers-to-dental-attendance -->
      dental-attendance-profile --> number-of-sound-teeth]. A direct relationship, SES 
      -> number-of-sound-teeth, is also significant.

PMID- 18096894
TI  - Premature stop codon in MMP20 causing amelogenesis imperfecta.
AB  - Proteolytic enzymes are necessary for the mineralization of dental enamel during
      development, and mutations in the kallikrein 4 (KLK4) and enamelysin (MMP20)
      genes cause autosomal-recessive amelogenesis imperfecta (ARAI). So far, only one
      KLK4 and two MMP20 mutations have been reported. We have identified an ARAI
      causing point mutation (c.102G>A, g.102G>A, and p.W34X) in exon 1 of MMP20 in a
      proband with autosomal-recessive hypoplastic-hypomaturation amelogenesis
      imperfecta. The G to A transition changes the tryptophan (W) codon (TGG) at amino
      acid position 34 into a translation termination (X) codon (TGA). No disease
      causing sequence variations were detected in KLK4. The affected enamel is thin,
      with mild spacing in the anterior dentition. The enamel layer is hypomineralized,
      does not contrast with dentin on radiographs, and tends to chip away from the
      underlying dentin. An intrinsic yellowish pigmentation is evident, even during
      eruption. The phenotype supports current ideas concerning the function of
      enamelysin.

PMID- 18096896
TI  - Anxiety and ability to recognize clinical information in dentistry.
AB  - Stress significantly affects a person's cognitive ability to process information.
      Therefore, we hypothesized that patients' ability to recognize information
      related to the procedure they are about to undergo will be affected by the
      stressfulness of the situation (less recognition under a high-stress situation as
      compared with a low-stress situation). Patients (n = 66) were evaluated for their
      ability to recognize clinical information supplied on two different occasions:
      immediately before oral surgery (high-stress condition) and before suture removal
      (low-stress condition). Dental and state of anxiety and expectation of pain were
      also assessed. On both occasions, the patients' ability to recognize information
      correctly was low (less than 50%). Patients recognized significantly less
      information pre-operatively than before suture removal. State of anxiety, dental
      anxiety, and expectation to experience pain had a profound effect on their
      ability to recognize provided information correctly. Apparently, before dental
      treatment (high or low on stress), patients' ability to process information may
      be severely impaired.

PMID- 18096897
TI  - Trajectory patterns of dental caries experience in the permanent dentition to the
      fourth decade of life.
AB  - Dental caries is a chronic, cumulative disease, but no studies have investigated
      longitudinal patterns of caries experience. The objective of this study was to
      identify and describe developmental trajectories of caries experience in the
      permanent dentition to age 32. Longitudinal caries data for 955 participants in a
      longstanding birth cohort study were analyzed by trajectory analysis. Three
      caries experience trajectories were identified by the SAS macro PROC TRAJ; these
      were categorized as "high" (approximately 15%), "medium" (approximately 43%), and
      "low" (approximately 42%) DMFS (Decayed, Missing, and Filled Surfaces). All were
      relatively linear, although the higher trajectories were more "S-shaped". This
      effect disappeared following adjustment for the number of unaffected surfaces
      remaining at each age, suggesting that, among individuals following a similar
      caries trajectory, caries rate is relatively constant across time.

PMID- 18096898
TI  - The relationship between periodontitis and preterm low birthweight.
AB  - There is no consensus about the influence of periodontal disease on preterm low
      birthweight. The objective was to investigate the relationship between
      periodontal disease and preterm low birthweight. A case-control study with 542
      post partum women aged over 30 yrs was conducted. Three groups of cases were
      compared with non-preterm and non-low-birthweight control individuals (n = 393):
      low birthweight (n = 96), preterm (n = 110), and preterm and low birthweight (n =
      63). Periodontal clinical parameters and covariates were recorded. Periodontal
      disease levels were higher in control individuals than in cases. The extent of
      periodontal disease did not increase risk of preterm low birthweight according to
      15 measures of periodontal disease. Mean periodontal pocket depth and frequency
      of periodontal sites with clinical attachment level > or = 3 mm in preterm low
      birthweight cases were lower than in control individuals. Periodontal disease was
      not more severe in women with preterm low birthweight babies.

PMID- 18096899
TI  - No alteration in bone mineral density in patients with periodontitis.
AB  - Alveolar bone destruction can be magnified in the presence of generalized
      skeletal disorders. We questioned whether severe generalized periodontitis
      patients display signs of bone metabolism disturbances. Our objective was to
      assess skeletal bone mineral density (BMD) and biochemical bone parameters in
      premenopausal women with periodontitis. Forty-five patients and 40 control
      individuals were included in the study. We measured BMD by dual-energy x-ray
      absorptiometry. The results showed no difference in BMD values between the
      periodontitis and control groups (p > 0.05). A positive relationship between the
      clinical attachment level and Body Mass Index (BMI) scores was observed (p =
      0.03). Increased serum creatinine levels were noted in the periodontitis group (p
      = 0.04). Analysis of the data suggests that there is no evidence for an
      association between skeletal BMD and severe periodontitis in premenopausal women.
      There may be a link between elevated creatinine levels and periodontitis. The
      persons with high BMI scores seemed to be at risk for periodontitis.

PMID- 18096900
TI  - Refractive index mismatch and monomer reactivity influence composite curing
      depth.
AB  - Limited cure depth is a drawback of light-activated composites. We hypothesize
      that curing light transmission and cure depth are influenced by monomer
      reactivity and filler/resin refractive index mismatch. Light transmission
      throughout cure was recorded for composites based on strontium (refractive index
      1.51) or barium (refractive index 1.53) glass fillers. Fillers were mixed (70
      wt%) with 4 bisphenol-A diglycidyl-ether-dimethacrylate (bis-GMA):triethylene
      glycol dimethacrylate (TEGDMA) formulations with refractive indices ranging from
      1.4703 to 1.5370. Following polymerization, cure depth and pre- and post-cure
      translucency parameters were determined. Transmission changes and cure depths
      related to monomer reactivity and filler/resin refractive index mismatch with
      significant interaction. Composites became more opaque or translucent on curing.
      Optimizing filler/resin refractive index mismatch provides increased curing depth
      and assists shade-matching.

PMID- 18096901
TI  - Microtensile specimen attachment and shape--finite element analysis.
AB  - Microtensile bond strength values are influenced by specimen shape and attachment
      method to the gripping device during testing. We hypothesized that stress
      distribution inside the testing specimen is affected by microtensile specimen
      shape and attachment method. Rectangular, hourglass-, and dumbbell-shaped
      specimens, all with a 1 mm(2) cross-sectional testing region, were modeled as
      indirect ceramic restorations luted to dentin. Three specimen attachments were
      investigated: (1) posterior surface; (2) posterior, superior, and lateral
      surfaces; and (3) all surfaces. Qualitative and quantitative analyses were
      carried out according to von Mises' criteria. Stress analysis showed a direct
      correlation between attachment modes and stress distribution, with shear stresses
      observed in models with less surface attachment. Increasing the number of faces
      for specimen attachment to the metallic gripping device resulted in a more
      homogeneous and regular distribution of stress, with tensile stress concentrated
      at the adhesive interface. Dumbbell-shaped specimens showed improved stress
      distribution compared with rectangular and hourglass-shaped specimens.

PMID- 18096902
TI  - Automatic classification of foot examination findings using clinical notes and
      machine learning.
AB  - We examine the feasibility of a machine learning approach to identification of
      foot examination (FE) findings from the unstructured text of clinical reports. A
      Support Vector Machine (SVM) based system was constructed to process the text of
      physical examination sections of in- and out-patient clinical notes to identify
      if the findings of structural, neurological, and vascular components of a FE
      revealed normal or abnormal findings or were not assessed. The system was tested
      on 145 randomly selected patients for each FE component using 10-fold cross
      validation. The accuracy was 80%, 87% and 88% for structural, neurological, and
      vascular component classifiers, respectively. Our results indicate that using
      machine learning to identify FE findings from clinical reports is a viable
      alternative to manual review and warrants further investigation. This application
      may improve quality and safety by providing inexpensive and scalable methodology
      for quality and risk factor assessments at the point of care.

PMID- 18096904
TI  - Promoting electronic health record adoption. Is it the correct focus?

PMID- 18096903
TI  - Use of a regional health information exchange to detect crossover of patients
      with MRSA between urban hospitals.
AB  - BACKGROUND: A significant portion of patients already known to be colonized or
      infected with Methicillin-Resistant Staphylococcus aureus (MRSA) may not be
      identified at admission by neighboring hospitals. METHODS: We utilized data from
      a Regional Health Information Exchange to assess the frequency that patients
      known to have MRSA at one healthcare system are admitted to a neighboring
      healthcare system unaware of their MRSA status. We conducted a retrospective,
      registry trial from January 1999 through January 2006 involving three healthcare
      systems in central Indianapolis, representing six hospitals. RESULTS: Over one
      year, 286 unique patients generated 587 admissions accounting for 4,335 inpatient
      days where the receiving hospital was not aware of the prior history of MRSA. The
      patients accounted for an additional 10% of MRSA admissions received by study
      hospitals over one year and over 3,600 inpatient days without contact isolation.
      CONCLUSIONS: Information exchange could improve timely identification of known
      MRSA patients within an urban setting.

PMID- 18096905
TI  - Impact of research-based synopses delivered as daily e-mail: a prospective
      observational study.
AB  - We conducted a prospective observational study to (1) determine usage and
      construct validity of a method to gauge the cognitive impact of information
      derived from daily e-mail, and (2) describe self-reported impacts of research
      based synopses (InfoPOEMs) delivered as e-mail. Ratings of InfoPOEMs using an
      Impact assessment scale provided (a) data on usage of the impact assessment
      method, (b) reports of impact by InfoPOEM and by doctor and (c) data for analysis
      of construct validity of the scale. PARTICIPANTS were family physicians or
      general practitioners who rated at least five InfoPOEMs delivered on e-mail. For
      each InfoPOEM rated, 0.1 continuing education credit was awarded by the College
      of Family Physicians of Canada. Use of the impact assessment scale linked to a
      daily InfoPOEM was sustained during the 150-day study period. 1,007 participants
      submitted 61,493 reports of 'cognitive impact' by rating on average 61 InfoPOEMs
      (range 5-111). 'I learned something new' was most frequently reported. 'I was
      frustrated as there was not enough information or nothing useful' was the most
      frequently reported negative type of impact. The proportion of reports of 'No
      Impact' varied substantially across individual InfoPOEMs. Impact patterns
      suggested an 8 or 9-factor solution. Our Impact assessment method facilitates
      knowledge transfer by promoting two-way exchange between providers of health
      information and family doctors. Providers of health information can use this
      method to better understand the impact of research-based synopses. Sustaining
      current practice and increasing knowledge about new developments in medicine are
      important outcomes arising from research-based synopses delivered as e-mail, in
      addition to practice change.

PMID- 18096906
TI  - A heuristic indication and warning staging model for detection and assessment of
      biological events.
AB  - OBJECTIVE: This paper presents a model designed to enable rapid detection and
      assessment of biological threats that may require swift intervention by the
      international public health community. DESIGN: We utilized Strauss' grounded
      theory to develop an expanded model of social disruption due to biological events
      based on retrospective and prospective case studies. We then applied this model
      to the temporal domain and propose a heuristic staging model, the Wilson-Collmann
      Scale for assessing biological event evolution. MEASUREMENTS: We retrospectively
      and manually examined hard copy archival local media reports in the native
      vernacular for three biological events associated with substantial social
      disruption. The model was then tested prospectively through media harvesting
      based on keywords corresponding to the model parameters. RESULTS: Our heuristic
      staging model provides valuable information about the features of a biological
      event that can be used to determine the level of concern warranted, such as
      whether the pathogen in question is responding to established public health
      disease control measures, including the use of antimicrobials or vaccines;
      whether the public health and medical infrastructure of the country involved is
      adequate to mount the necessary response; whether the country's officials are
      providing an appropriate level of information to international public health
      authorities; and whether the event poses a international threat. The approach is
      applicable for monitoring open-source (public-domain) media for indications and
      warnings of such events, and specifically for markers of the social disruption
      that commonly occur as these events unfold. These indications and warnings can
      then be used as the basis for staging the biological threat in the same manner
      that the United States National Weather Service currently uses storm warning
      models (such as the Saffir-Simpson Hurricane Scale) to detect and assess
      threatening weather conditions. CONCLUSION: Used as a complement to current
      epidemiological surveillance methods, our approach could aid global public health
      officials and national political leaders in responding to biological threats of
      international public health significance.

PMID- 18096907
TI  - The BRIDG project: a technical report.
AB  - OBJECTIVES: The Biomedical Research Integrated Domain Group (BRIDG) project is a
      collaborative initiative between the National Cancer Institute (NCI), the
      Clinical Data Interchange Standards Consortium (CDISC), the Regulated Clinical
      Research Information Management Technical Committee (RCRIM TC) of Health Level 7
      (HL7), and the Food and Drug Administration (FDA) to develop a model of the
      shared understanding of the semantics of clinical research. DESIGN: The BRIDG
      project is based on open-source collaborative principles and an implementation
      independent, use-case driven approach to model development. In the BRIDG model,
      declarative and procedural knowledge are represented using the Unified Modeling
      Language (UML) class, activity and state diagrams. MEASUREMENTS: The BRIDG model
      currently contains harmonized semantics from four project use cases: the
      caXchange project and the patient study calendar project from caBIG; the standard
      data tabular model (SDTM) from CDISC; and the regulated products submission model
      (RPS) from HL7. Scalable harmonization processes have been developed to expand
      the model with content from additional use cases. RESULTS: The first official
      release of the BRIDG model was published in June 2007. Use of the BRIDG model by
      the NCI has supported the rapid development of semantic interoperability across
      applications within the caBIG program. CONCLUSIONS: The BRIDG project has brought
      together different standards communities to clarify the semantics of clinical
      research across pharmaceutical, regulatory, and research organizations.
      Currently, the NCI uses the BRIDG model to support interoperable application
      development in the caBIG, and CDISC and HL7 are using the BRIDG model to support
      standards development.

PMID- 18096908
TI  - HealthMap: global infectious disease monitoring through automated classification
      and visualization of Internet media reports.
AB  - OBJECTIVE: Unstructured electronic information sources, such as news reports, are
      proving to be valuable inputs for public health surveillance. However, staying
      abreast of current disease outbreaks requires scouring a continually growing
      number of disparate news sources and alert services, resulting in information
      overload. Our objective is to address this challenge through the HealthMap.org
      Web application, an automated system for querying, filtering, integrating and
      visualizing unstructured reports on disease outbreaks. DESIGN: This report
      describes the design principles, software architecture and implementation of
      HealthMap and discusses key challenges and future plans. MEASUREMENTS: We
      describe the process by which HealthMap collects and integrates outbreak data
      from a variety of sources, including news media (e.g., Google News), expert
      curated accounts (e.g., ProMED Mail), and validated official alerts. Through the
      use of text processing algorithms, the system classifies alerts by location and
      disease and then overlays them on an interactive geographic map. We measure the
      accuracy of the classification algorithms based on the level of human curation
      necessary to correct misclassifications, and examine geographic coverage.
      RESULTS: As part of the evaluation of the system, we analyzed 778 reports with
      HealthMap, representing 87 disease categories and 89 countries. The automated
      classifier performed with 84% accuracy, demonstrating significant usefulness in
      managing the large volume of information processed by the system. Accuracy for
      ProMED alerts is 91% compared to Google News reports at 81%, as ProMED messages
      follow a more regular structure. CONCLUSION: HealthMap is a useful free and open
      resource employing text-processing algorithms to identify important disease
      outbreak information through a user-friendly interface.

PMID- 18096909
TI  - caGrid 1.0: an enterprise Grid infrastructure for biomedical research.
AB  - OBJECTIVE: To develop software infrastructure that will provide support for
      discovery, characterization, integrated access, and management of diverse and
      disparate collections of information sources, analysis methods, and applications
      in biomedical research. DESIGN: An enterprise Grid software infrastructure,
      called caGrid version 1.0 (caGrid 1.0), has been developed as the core Grid
      architecture of the NCI-sponsored cancer Biomedical Informatics Grid (caBIG)
      program. It is designed to support a wide range of use cases in basic,
      translational, and clinical research, including 1) discovery, 2) integrated and
      large-scale data analysis, and 3) coordinated study. MEASUREMENTS: The caGrid is
      built as a Grid software infrastructure and leverages Grid computing technologies
      and the Web Services Resource Framework standards. It provides a set of core
      services, toolkits for the development and deployment of new community provided
      services, and application programming interfaces for building client
      applications. RESULTS: The caGrid 1.0 was released to the caBIG community in
      December 2006. It is built on open source components and caGrid source code is
      publicly and freely available under a liberal open source license. The core
      software, associated tools, and documentation can be downloaded from the
      following URL: https://cabig.nci.nih.gov/workspaces/Architecture/caGrid.
      CONCLUSIONS: While caGrid 1.0 is designed to address use cases in cancer
      research, the requirements associated with discovery, analysis and integration of
      large scale data, and coordinated studies are common in other biomedical fields.
      In this respect, caGrid 1.0 is the realization of a framework that can benefit
      the entire biomedical community.

PMID- 18096910
TI  - Characteristics of effective electronic mail messages distributed to healthcare
      professionals in a hospital setting.
AB  - Electronic mailing systems (e-mail) are an important means to disseminate
      information within electronic networks. However, in large business communities
      including the hectic environment of hospitals it may be difficult to induce
      account holders to read the e-mail. In two mailings disseminated in a large
      university hospital we evaluated the impact of e-mail layout (three e-mail text
      versions, two e-mails with graphics) on the willingness of its approximately 6500
      recipients to seek additional electronic information and open an integrated link.
      Overall access rates after 90 days were 21.1 and 23.5% with more than 70% of the
      respondents opening the link within 3 days. Differences between different layouts
      were large and artwork text, HTML text, animated GIF, and static image prompted
      1.2, 1.7, 1.8, and 2.3 times more often access than the courier plain text
      message (p <or= 0.001). This study revealed that layout is a major determinant of
      the success of an information campaign.

PMID- 18096911
TI  - Exchange of computable patient data between the Department of Veterans Affairs
      (VA) and the Department of Defense (DoD): terminology mediation strategy.
AB  - Complete patient health information that is available where and when it is needed
      is essential to providers and patients and improves healthcare quality and
      patient safety. VA and DoD have built on their previous experience in patient
      data exchange to establish data standards and terminology services to enable real
      time bi-directional computable (i.e., encoded) data exchange and achieve semantic
      interoperability in compliance with recommended national standards and the eGov
      initiative. The project uses RxNorm, UMLS, and SNOMED CT terminology standards to
      mediate codified pharmacy and allergy data with greater than 92 and 60 percent
      success rates respectively. Implementation of the project has been well received
      by users and is being expanded to multiple joint care sites. Stable and mature
      standards, mediation strategies, and a close relationship between healthcare
      institutions and Standards Development Organizations are recommended to achieve
      and maintain semantic interoperability in a clinical setting.

PMID- 18096912
TI  - Individual and joint expert judgments as reference standards in artifact
      detection.
AB  - OBJECTIVE: To investigate the agreement among clinical experts in their judgments
      of monitoring data with respect to artifacts, and to examine the effect of
      reference standards that consist of individual and joint expert judgments on the
      performance of artifact filters. DESIGN: Individual judgments of four physicians,
      a majority vote judgment, and a consensus judgment were obtained for 30 time
      series of three monitoring variables: mean arterial blood pressure (ABPm),
      central venous pressure (CVP), and heart rate (HR). The individual and joint
      judgments were used to tune three existing automated filtering methods and to
      evaluate the performance of the resulting filters. MEASUREMENTS: The interrater
      agreement was calculated in terms of positive specific agreement (PSA). The
      performance of the artifact filters was quantified in terms of sensitivity and
      positive predictive value (PPV). RESULTS: PSA values between 0.33 and 0.85 were
      observed among clinical experts in their selection of artifacts, with relatively
      high values for CVP data. Artifact filters developed using judgments of
      individual experts were found to moderately generalize to new time series and
      other experts; sensitivity values ranged from 0.40 to 0.60 for ABPm and HR
      filters (PPV: 0.57-0.84), and from 0.63 to 0.80 for CVP filters (PPV: 0.71-0.86).
      A higher performance value for the filters was found for the three variable types
      when joint judgments were used for tuning the filtering methods. CONCLUSION:
      Given the disagreement among experts in their individual judgment of monitoring
      data with respect to artifacts, the use of joint reference standards obtained
      from multiple experts is recommended for development of automatic artifact
      filters.

PMID- 18096913
TI  - Supporting patient care in the emergency department with a computerized
      whiteboard system.
AB  - Efficient information management and communication within the emergency
      department (ED) is essential to providing timely and high-quality patient care.
      The ED whiteboard (census board) usually serves as an ED's central access point
      for operational and patient-related information. This article describes the
      design, functionality, and experiences with a computerized ED whiteboard, which
      has the ability to display relevant operational and patient-related information
      in real time. Embedded functionality, additional whiteboard views, and the
      integration with ED and institutional information system components, such as the
      computerized patient record or the provider order entry system, provide rapid
      access to more detailed information. As an information center, the computerized
      whiteboard supports our ED environment not only for providing patient care, but
      also for operational, educational, and research activities.

PMID- 18096914
TI  - Training multidisciplinary biomedical informatics students: three years of
      experience.
AB  - OBJECTIVE: The European INFOBIOMED Network of Excellence recognized that a
      successful education program in biomedical informatics should include not only
      traditional teaching activities in the basic sciences but also the development of
      skills for working in multidisciplinary teams. DESIGN: A carefully developed 3
      year training program for biomedical informatics students addressed these
      educational aspects through the following four activities: (1) an internet course
      database containing an overview of all Medical Informatics and BioInformatics
      courses, (2) a BioMedical Informatics Summer School, (3) a mobility program based
      on a 'brokerage service' which published demands and offers, including funding
      for research exchange projects, and (4) training challenges aimed at the
      development of multi-disciplinary skills. MEASUREMENTS: This paper focuses on
      experiences gained in the development of novel educational activities addressing
      work in multidisciplinary teams. The training challenges described here were
      evaluated by asking participants to fill out forms with Likert scale based
      questions. For the mobility program a needs assessment was carried out. RESULTS:
      The mobility program supported 20 exchanges which fostered new BMI research,
      resulted in a number of peer-reviewed publications and demonstrated the
      feasibility of this multidisciplinary BMI approach within the European Union.
      Students unanimously indicated that the training challenge experience had
      contributed to their understanding and appreciation of multidisciplinary
      teamwork. CONCLUSION: The training activities undertaken in INFOBIOMED have
      contributed to a multi-disciplinary BMI approach. It is our hope that this work
      might provide an impetus for training efforts in Europe, and yield a new
      generation of biomedical informaticians.

PMID- 18096915
TI  - User acceptance of HIV TIDES--Tailored Interventions for Management of Depressive
      Symptoms in persons living with HIV/AIDS.
AB  - OBJECTIVE: The Tailored Interventions for management of DEpressive Symptoms
      (TIDES) program was designed based on social cognitive theory to provide
      tailored, computer-based education on key elements and self-care strategies for
      depressive symptoms in persons living with HIV/AIDS (PLWHAs). DESIGN AND
      MEASUREMENT: Based on an extension of the Technology Acceptance Model (TAM), a
      cross-sectional design was used to assess the acceptance of the HIV TIDES
      prototype and explore the relationships among system acceptance factors proposed
      in the conceptual model. RESULTS: Thirty-two PLWHAs were recruited from HIV/AIDS
      clinics. The majority were African American (68.8%), male (65.6%), with high
      school or lower education (68.7%), and in their 40s (62.5%). PARTICIPANTS spent
      an average of 10.4 minutes (SD = 5.6) using HIV TIDES. The PLWHAs rated the
      system as easy to use (Mean = 9.61, SD = 0.76) and useful (Mean = 9.50, SD =
      1.16). The high ratings of behavior intention to use (Mean = 9.47, SD = 1.24)
      suggest that HIV TIDES has the potential to be accepted and used by PLWHAs. Four
      factors were positively correlated with behavioral intention to use: perceived
      usefulness (r = 0.61), perceived ease of use (r = 0.61), internal control (r =
      0.59), and external control (r = 0.46). Computer anxiety (r = -0.80), tailoring
      path (r = 0-.35) and depressive symptoms (r = -0.49) were negatively correlated
      with behavioral intention to use. CONCLUSION: The results of this study provide
      evidence of the acceptability of HIV TIDES by PLWHAs. Individuals are expected to
      be empowered through participating in the interactive process to generate their
      self-care plan. HIV TIDES enables information sharing about depression prevention
      and health promotion and has the potential to reframe the traditional patient
      provider relationship.

PMID- 18096916
TI  - Identifying organizational capacities and incentives for clinical data-sharing:
      the case of a regional perinatal information system.
AB  - The development of regional data-sharing among healthcare organizations is viewed
      as an important step in the development of health information technology (HIT),
      but little is known about this complex task. This is a case study of a regional
      perinatal data system that involved four hospitals, together responsible for over
      10,000 births annually. Using standard qualitative methods, we chronicled project
      milestones, and identified 31 "critical incidents" that delayed or prevented
      their achievement. We then used these critical incidents to articulate six
      organizational capacity domains associated with the achievement of project
      milestones, and a seventh domain consisting of organizational incentives.
      Finally, we analyzed the relationship of milestone achievement to the presence of
      these capacities and incentives. This data center case suggests four requirements
      for sharing data across organizations: 1) a readiness assessment; 2) a perceived
      mandate; 3) a formal governance structure; and 4) a third party IT component.

PMID- 18096917
TI  - Contextual implementation model: a framework for assisting clinical information
      system implementations.
AB  - OBJECTIVE: This paper presents a multiple perspectives model of clinical
      information system implementation, the CONTEXTual Implementation Model (CIM).
      Although other implementation models have been developed, few are grounded in
      data and others fail to take adequate account of the clinical environment and
      users' requirements. DESIGN: The CIM arose from qualitative data collected from
      four clinical units in two large Australian teaching hospitals. The aim of the
      study was to explore physicians' test management work practices associated with
      the compulsory use of a hospital-wide, mandatory computerized provider order
      entry (CPOE) system.(1) The dataset consisted of non-participatory observations
      of physicians using CPOE (n=55 sessions) and interviews with health professionals
      (n=28) about test management work practices. Data were analyzed by two
      researchers independently using an iterative grounded approach. RESULTS: A core
      underlying theme of 'contextual differences' emerged which explained physicians'
      use of the CPOE system in the sites. The CIM focuses attention on diversity at
      three contextual levels: the organizational level; the clinical or departmental
      level, and the individual level. Within each of these levels there are dimensions
      for consideration (for example, organizational culture, leadership and diverse
      ways of working) which affect physicians' attitudes to, and use of, CPOE.
      CONCLUSION: The CIM provides a contextual differences perspective which can be
      used to facilitate the implementation of clinical information systems. Developing
      a clinical information system implementation model serves as a framework to guide
      future implementations to ensure their safe and efficient use and also improve
      the likelihood of uptake by physicians.

PMID- 18096918
TI  - A randomized effectiveness trial of a clinical informatics consult service:
      impact on evidence-based decision-making and knowledge implementation.
AB  - OBJECTIVE: To determine the effectiveness of providing synthesized research
      evidence to inform patient care practices via an evidence based informatics
      program, the Clinical Informatics Consult Service (CICS). DESIGN: Consults were
      randomly assigned to one of two conditions: CICS Provided, in which clinicians
      received synthesized information from the biomedical literature addressing the
      consult question or No CICS Provided, in which no information was provided.
      MEASUREMENT: Outcomes were measured via online post-consult forms that assessed
      consult purpose, actual and potential impact, satisfaction, time spent searching,
      and other variables. RESULTS: Two hundred twenty six consults were made during
      the 19-month study period. Clinicians primarily made requests in order to update
      themselves (65.0%, 147/226) and were satisfied with the service results (Mean
      4.52 of possible 5.0, SD 0.94). Intention to treat (ITT) analyses showed that
      consults in the CICS Provided condition had a greater actual and potential impact
      on clinical actions and clinician satisfaction than No CICS consults. Evidence
      provided by the service primarily impacted the use of a new or different
      treatment (OR 8.19 95% CI 1.04-64.00). Reasons for no or little impact included a
      lack of evidence addressing the issue or that the clinician was already
      implementing the practices indicated by the evidence. CONCLUSIONS: Clinical
      decision-making, particularly regarding treatment issues, was statistically
      significantly impacted by the service. Programs such as the CICS may provide an
      effective tool for facilitating the integration of research evidence into the
      management of complex patient care and may foster clinicians' engagement with the
      biomedical literature.

PMID- 18096919
TI  - Selective separation of the major whey proteins using ion exchange membranes.
AB  - Synthetic microporous membranes with functional groups covalently attached were
      used to selectively separate beta-lactoglobulin, BSA, and alpha-lactalbumin from
      rennet whey. The selectivity and membrane performance of strong (quaternary
      ammonium) and weak (diethylamine) ion-exchange membranes were studied using
      breakthrough curves, measurement of binding capacity, and protein composition of
      the elution fraction to determine the binding behavior of each membrane. When the
      weak and strong anion exchange membranes were saturated with whey, they were both
      selective primarily for beta-lactoglobulin with less than 1% of the eluate
      consisting of alpha-lactalbumin or BSA. The binding capacity of a pure beta
      lactoglobulin solution was in excess of 1.5 mg/cm2 of membrane. This binding
      capacity was reduced to approximately 1.2 mg/cm2 when using a rennet whey
      solution (pH 6.4). This reduction in protein binding capacity can be explained by
      both the competitive effects of other whey proteins and the effect of ions
      present in whey. Using binary solution breakthrough curves and rennet whey
      breakthrough curves, it was shown that alpha-lactalbumin and BSA were displaced
      from the strong and weak anion exchange membranes by beta-lactoglobulin. Finally,
      the effect of ionic strength on the binding capacity of individual proteins for
      each membrane was determined by comparing model protein solutions in milk
      permeate (pH 6.4) and a 10 mM sodium phosphate buffer (pH 6.4). Binding
      capacities of beta-lactoglobulin, alpha-lactalbumin, and BSA in milk permeate
      were reduced by as much as 50%. This reduction in capacity coupled with the low
      binding capacity of current ion exchange membranes are 2 serious considerations
      for selectively separating complex and concentrated protein solutions.

PMID- 18096920
TI  - Release of butylated hydroxytoluene from an active film packaging to Asadero
      cheese and its effect on oxidation and odor stability.
AB  - Antioxidant active packaging consisting of coextruded films made of low density
      polyethylene (LDPE) added with 0, 8, and 14 mg/g of butylated hydroxytoluene
      (BHT) and polyamide 6/66 were fabricated. The release of BHT from the films to
      Asadero cheese was determined. Most of the BHT was diffused from the LDPE layer
      to the cheese during the first 20 d of storage at 5 degrees C. Diffusion
      coefficient for the diffusion of BHT from the films 8 and 14 to the cheese was
      calculated as 6.24E-12 and 6.26E-12 cm2/s, respectively. The release of BHT from
      the film added with 8 mg/g of the antioxidant in the LDPE layer complied with the
      legal limit established for food products. However, the film added with 14 mg/g
      of the antioxidant exceeded that limit. The film added with 8 mg/g of BHT
      maintained the same levels of oxidized odor from 20 to 100 d of storage.

PMID- 18096921
TI  - Effect of a diet enriched in whole linseed and sunflower oil on goat milk fatty
      acid composition and conjugated linoleic acid isomer profile.
AB  - The aim of the present research was to study changes in milk composition and
      fatty acid profile, specifically conjugated linoleic acid (CLA) and its isomers,
      in goat milk as affected by dietary supplementation of sun-flower oil and whole
      linseed (0.81 and 1.84% of dry matter on basal diet, respectively) and to assess
      the persistency of the response. To achieve this objective, bulk milk from a herd
      and from 6 individual dairy goats fed a diet supplemented with sunflower oil and
      whole linseed was monitored for a period of 3 mo. Gas chromatography and silver
      ion HPLC were used to analyze total CLA content and the isomeric profile of these
      fatty acids, respectively. The contents of alpha-linolenic acid increased from
      0.35% with the reference diet to 0.62% with the supplemented diet. Similarly, CLA
      milk content increased from 0.46 to 1.18%. The same pattern was also observed for
      trans-11 C18:1 (1.38 to 4.05%, respectively) in goat milk after 3 mo of lipid
      supplementation. In contrast, changes in other trans C18:1 isomers were less
      remarkable. There was a strong linear correlation between cis-9, trans-11 C18:2,
      the main CLA isomer, and trans-11 C18:1 under the conditions assayed and their
      concentration remained stable throughout the duration of the study. Levels of the
      minor CLA isomers were also enhanced as a consequence of lipid supplementation.
      The most remarkable increases were observed for 11-13 (trans-trans and trans-cis
      geometric isomers), whereas trans-7, cis-9 (the second most important CLA isomer
      from a quantitative point of view) and trans-10, cis-12 increased only slightly
      with lipid supplementation.

PMID- 18096922
TI  - Occurrence of the angiotensin-converting enzyme inhibiting tripeptides Val-Pro
      Pro and Ile-Pro-Pro in different cheese varieties of Swiss origin.
AB  - The contents of the 2 antihypertensive peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro
      (IPP) were determined in 101 samples from 10 different Swiss cheese varieties
      using HPLC with subsequent triple mass spectrometry. In the category of extra
      hard and hard cheeses, the Protected Denomination of Origin cheeses Berner
      Alpkase and Berner Hobelkase, L'Etivaz a rebibes, Le Gruyere, Sbrinz, Emmentaler
      (organic and conventional) and in the category of semihard cheeses, the varieties
      Tilsiter, Appenzeller 1/4 fat and full fat, Tete de Moine, and Vacherin
      fribourgeois were screened in the study. The average concentration of the sum of
      VPP and IPP in the screened cheese varieties varied to a large extent, and
      substantial variations were obtained for individual samples within the cheese
      varieties. The lowest average concentration of the 2 tri-petides was found in
      L'Etivaz a rebibes (n = 3) at 19.1 mg/kg, whereas Appenzeller 1/4 fat (n = 4)
      contained the greatest concentration at 182.2 mg/kg. In individual samples, the
      total concentration of VPP and IPP varied between 1.6 and 424.5 mg/kg. With the
      exception of a 10-yr-old cheese, VPP was always present at greater concentrations
      than IPP. Milk pretreatment, cultures, scalding conditions, and ripening time
      were identified as the key factors influencing the concentration of these 2
      naturally occurring bioactive peptides in cheese. The results of the present
      study show that various traditional cheese varieties contain, on average, similar
      concentrations of the 2 antihypertensive peptides to the recently developed
      fermented milk products with blood pressure-lowering property. This may serve as
      a basis for the development of a functional cheese with blood pressure-lowering
      property.

PMID- 18096923
TI  - Influence of emulsifying salts on the textural properties of nonfat process
      cheese made from direct acid cheese bases.
AB  - The objective of this study was to investigate the influence of several types of
      emulsifying salts (ES) on the texture of nonfat process cheese (NFPC). Improperly
      produced nonfat cheese tends to exhibit several problems upon baking including
      stickiness, insufficient or excessive melt, pale color upon cooling, formation of
      a dry skin (skinning) often leading to dark blistering, and chewy texture. These
      attributes are due to the strength and number of interactions between and among
      casein molecules. We propose to disrupt these interactions by using suitable
      emulsifying salts (ES). These ES chelate Ca and disperse caseins. Stirred curd
      cheese bases were made from skim milk using direct acidification with lactic acid
      to pH values 5.0, 5.2, and 5.4, and ripened for 1 d. Various levels of trisodium
      citrate (TSC; 0.5, 1, 1.5, 2, 2.5, 3, and 5%), disodium phosphate (DSP; 1, 2, 3,
      and 4%), or trisodium phosphate (TSP; 1, 2, 3, and 4%) were blended with the
      nonfat cheese base. Cheese, ES, and water were weighed into a steel container,
      which was placed in a waterbath at 98 degrees C and then stirred using an
      overhead stirrer for 9 min. Molten cheese was poured into plastic containers,
      sealed, and stored at 4 degrees C for 7 d before analysis. Texture and melting
      properties were determined using texture profile analysis and the UW-Melt
      profiler. The pH 5.2 and 5.4 cheese bases were sticky during manufacture and had
      a pale straw-like color, whereas the pH 5.0 curd was white. Total calcium
      contents were approximately 400, 185, and 139 mg/100 g for pH 5.4, 5.2, and 5.0
      cheeses, respectively. Addition of DSP resulted in NFPC with the lowest extent of
      flow, and crystal formation was apparent at DSP levels above 2%. The NFPC
      manufactured from the pH 5.0 base and using TSP had reduced melt and increased
      stickiness, whereas melt was significantly increased and stickiness was reduced
      in NFPC made with pH 5.4 base and TSP. However, for NFPC made from the pH 5.4
      cheese and with 1% TSP, the pH value was >6.20 and crystals were observed within
      a few days. Use of TSC increased extent of flow up to a maximum with the addition
      of 2% ES for all 3 types of cheese bases. Addition of high levels of TSC to the
      pH 5.2 and 5.4 cheese bases resulted in increased stickiness. Similar pH trends
      for attributes such as extent of flow, hardness, and adhesiveness were observed
      for both phosphate ES but no consistent pH trends were observed for the NFPC made
      with TSC. These initial trials suggest that the pH 5.0 cheese base was promising
      for further research and scale-up to pilot-scale process cheese making, because
      cheeses had a creamy color, reasonable melt, and did not have high adhesiveness
      when TSC was used as the ES. However, the acid whey produced from the pH 5.0 curd
      could be a concern.

PMID- 18096924
TI  - Evaluation of aroma generation of Lactococcus lactis with an electronic nose and
      sensory analysis.
AB  - There is an increased interest in exploring the potential of new Lactococcus
      lactis strains isolated from different natural ecosystems for the production of
      aroma compounds. Thus, the objective of this study was to screen the aroma
      generation of Lactococcus lactis strains isolated from different sources by an
      electronic nose and sensory evaluation for their potential use in starter cheese
      cultures. Twenty-three strains of Lactococcus lactis were isolated from dairy
      sources such as artisanal raw-milk cheeses, nondairy sources, and commercial
      starter cultures (industrial). All the strains were assessed for their ability to
      produce aromas by an electronic nose and sensory analysis after their incubation
      in milk. Some phenotypic characteristics of technological importance such as
      lactose fermentation, proteolytic activity, and citrate utilization were also
      evaluated. Lactococcus lactis strains showed clear phenotypic differences related
      to their isolation source. Strains isolated from raw-milk dairy products or
      commercial starter cultures presented faster lactose fermentation and proteolytic
      activity than those presented by strains isolated from nondairy sources.
      Additionally, strains isolated from dairy and nondairy sources presented better
      citrate utilization than strains isolated from commercial dairy starters. On the
      other hand, there was not a clear relationship between the source of isolation
      and the ability of lactococci strains to produce aroma. Principal components
      analysis of electronic nose data revealed 4 distinctive groups based on aroma
      profiles. Additionally, odor intensity scores (yogurt-like and Fresco cheese
      like) for these 4 groups revealed the nature of their differences. In general,
      strains from dairy products presented intense yogurt-like and Fresco cheese-like
      aromas, with the latter being the most intense for one specific strain. On the
      other hand, the majority of wild strains from nondairy sources presented a
      stronger yogurt-like aroma, whereas industrial strains presented low intensity
      for both aroma descriptors. Additionally, an aroma potentiation effect was
      observed when mixtures of 2 lactococci strains isolated from different sources
      acted together.

PMID- 18096925
TI  - Addition of pasture plant essential oil in milk: influence on chemical and
      sensory properties of milk and cheese.
AB  - The aim of this experiment was to study the effect of the addition, to milk, of
      an essential oil (EO) obtained from the hydrodistillation of plants collected
      from a mountain natural pasture on the milk and cheese sensory properties. The EO
      was mainly composed of terpenoid compounds (67 of the 95 compounds identified) as
      well as ketones, aldehydes, alcohols, esters, alkanes, and benzenic compounds. In
      milk, the addition of this EO at the concentration of 0.1 microL/L did not
      influence its sensory properties, whereas at 1.0 microL/L, sensory properties
      were modified. In cheeses, the effect of adding EO into milk was studied in an
      experimental dairy plant allowing the production of small Cantal-type cheeses (10
      kg) in 3 vats processed in parallel. The control (C) vat contained 110 L of raw
      milk; in the other 2 vats, 0.1 microL/L (EO1) or 3.0 microL/L (EO30) of EO were
      added to 110 L of the same milk. Six replicates were performed. After 5 mo of
      ripening, chemical and sensory analyses were carried out on the cheeses,
      including determination of the volatile compounds by dynamic headspace combined
      with gas chromatography-mass spectrometry. The EO did not influence the sensory
      properties of the cheeses at the lower concentration (EO1). However, the EO30
      cheeses had a more intense odor and aroma, both characterized as
      "mint/chlorophyll" and "thyme/oregano." These unusual odors and aromas originated
      directly from the EO added. In total, 152 compounds desorbing from cheese were
      found, of which 41 had been added with the EO; in contrast, 54 compounds of the
      EO were not recovered in the cheese. Few volatile compounds desorbing from
      cheeses, other than the added compounds, were affected by EO addition. Among
      them, 2-butanol, propanol, and 3-heptanone suggested a slight effect of the EO on
      lipid catabolism. The antimicrobial activity of terpenes is not or is only
      marginally involved in the explanation of the influence of the botanical
      composition of the meadows on the pressed cheeses sensory properties.

PMID- 18096926
TI  - Antimicrobial activity of nisin, reuterin, and the lactoperoxidase system on
      Listeria monocytogenes and Staphylococcus aureus in cuajada, a semisolid dairy
      product manufactured in Spain.
AB  - The inhibitory activity of nisin (N), reuterin (R), and the lactoperoxidase
      system (LPS), added individually or in combination, against Listeria
      monocytogenes and Staphylococcus aureus was investigated in "cuajada" (curdled
      milk), a semisolid dairy product manufactured in Spain. Cuajada was manufactured
      from UHT skim milk separately inoculated with L. monocytogenes and Staph. aureus,
      each at approximately 4 log cfu/mL, and held under conditions of temperature
      abuse (10 degrees C). On d 3, a synergistic bactericidal activity was observed
      for the combinations of biopreservatives assayed, with L. monocytogenes counts of
      only 0.30 log cfu/mL in cuajada made with N + R + LPS vs. 8.31 log cfu/mL in
      control cuajada. After 12 d, L. monocytogenes could not be detected in cuajada
      made with added N + LPS or N + R + LPS. Staphylococcus aureus was more resistant
      than L. monocytogenes to biopreservatives added individually. On d 3, the
      synergistic effect of the 3 biopreservatives against Staph. aureus resulted in
      counts of 3.03 log cfu/mL in cuajada made with N + R + LPS vs. 6.40 in control
      cuajada. After 12 d, Staph. aureus counts were 2.61 log cfu/mL in cuajada made
      with N + R + LPS, whereas they ranged from 6.11 to 7.70 log cfu/mL in control
      cuajada and in cuajada made with other combinations of biopreservatives. The most
      pronounced decrease in pathogen counts was achieved by the triple combination N +
      R + LPS, which acted synergistically on the inactivation of L. monocytogenes and
      Staph. aureus in cuajada over 12 d at 10 degrees C. The treatment combining these
      3 natural biopreservatives at low concentrations, within the hurdle concept of
      food preservation, might be a useful tool to control the growth of pathogenic
      microorganisms in nonacidified dairy products.

PMID- 18096927
TI  - Differences between Cheddar cheese manufactured by the milled-curd and stirred
      curd methods using different commercial starters.
AB  - Traditionally, Cheddar cheese is made by the milled-curd method. However, because
      of the mechanization of cheese making and time constraints, the stirred-curd
      method is more commonly used by many large-scale commercial manufacturers. This
      study was undertaken to evaluate quality differences during ripening (at 2 and 8
      degrees C) of Cheddar cheese made by the milled-curd and stirred-curd methods,
      using 4 different commercial starters. Twenty-four vats (4 starters x 2 methods x
      3 replicates) were made, with approximately 625 kg of pasteurized (72 degrees C x
      16 s) whole milk in each vat. Fat, protein, and salt contents of the cheeses were
      not affected by the starter. Starter cell densities in cheese were not affected
      by the method of manufacture. Nonstarter lactic acid bacteria counts at 90, 180,
      and 270 d were influenced by the manufacturing method, with a higher trend in
      milled-curd cheeses. Proteolysis in cheese (percentage of water-soluble N) was
      influenced by the starter and manufacturing method (270 d). Sensory analysis by a
      trained descriptive panel (n = 8) revealed differences in cooked, whey, sulfur,
      brothy, milk fat, umami, and bitter attributes caused by the starter, whereas
      only brothy flavor was influenced by storage temperature. The method of
      manufacture influenced diacetyl, sour, and salty flavors.

PMID- 18096928
TI  - Effect of prepartum photoperiod on milk production and prolactin concentration of
      dairy ewes.
AB  - Long photoperiods during established lactation increase milk production in dairy
      cattle and dairy sheep, but recent research in cattle and dairy goats suggests an
      additional influence of prepartum day length on milk yield in the subsequent
      lactation. The proposed mechanism of function is the level and role of
      circulating prolactin in mammary development. The objectives of this study were
      to evaluate the effect of prepartum photoperiod on milk production, milk
      composition, and prolactin concentration of 22 multiparous dairy ewes exposed to
      short day prepartum photoperiod (SDPP; 8 h of light:16 h of dark) or long day
      prepartum photoperiod (LDPP; 16 h of light:8 h of dark) for at least 6 wk
      prepartum. During the first 8 wk of lactation, SDPP ewes tended to produce more
      milk than LDPP ewes (2.43 vs. 2.29 kg/d, respectively), and the milk of SDPP ewes
      had a greater fat percentage than that of LDPP ewes (6.04 vs. 5.51%,
      respectively). Due to daily milk yield and greater fat content, SDPP ewes
      produced more 6.5% fat-corrected milk (+0.30 +/- 0.08 kg/d) and 6.5% fat- and
      5.8% protein-corrected milk (+0.28 +/- 0.08 kg/d) than LDPP ewes. For the
      lactation period of 180 d, SDPP ewes produced more test day milk than LDPP ewes
      (1.76 vs. 1.60 +/- 0.05 kg/d, respectively), but there were no differences in
      milk fat or protein percentages. Ewes in both treatments experienced a prolactin
      surge at lambing, but SDPP ewes had lower circulating prolactin concentration
      than LDPP ewes from 4 to 0.5 wk before lambing (14.7 vs. 51.3 +/- 4.2 mg/dL,
      respectively). These data suggest that decreased prepartum photoperiod may be
      important for increasing milk production in dairy ewes and may provide a
      management strategy for dairy sheep producers to increase milk yield.

PMID- 18096929
TI  - Cloning the genomic sequence and identification of promoter regions of bovine
      pyruvate carboxylase.
AB  - Pyruvate carboxylase (PC) catalyzes a pivotal reaction in gluconeogenesis and
      lipid metabolism in liver. In bovine the PC gene is expressed as six 5'
      untranslated region (UTR) mRNA variants. The objectives for this study were to
      clone and sequence the bovine PC gene, determine the intron and exon organization
      and identify PC promoter region(s). Oligonucleotide sequences that corresponded
      to the 5' UTR mRNA variants and coding sequence of bovine PC were used to isolate
      2 clones from the RPCI-42 bovine bacterial artificial chromosome (BAC) library.
      Sequencing data confirmed the presence of regions for the 5' UTR for bovine PC
      mRNA. The exon arrangement from 5' to 3' is 48 (exon I), 41 (exon II), 178 (exon
      IIIA and IIIB), and 185 (exon IV) bp. Three promoter regions, P3, P2, and P1,
      adjacent to exon I, II, and IIIA, respectively, were identified based on computer
      analysis of sequence data. Putative promoters were cloned into a firefly
      luciferase vector and transiently transfected into H4IIE rat hepatoma cells. All
      PC promoters demonstrated luciferase activity comparable with the minimal
      promoter luciferase vector and higher than the promoterless luciferase vector. In
      addition, PC promoter 1 exhibited greater luciferase activity compared with PC
      promoter 2 or 3. These data provide information about the arrangement of the 4
      bovine PC 5' UTR exons, the identity of the promoter regions for the bovine PC
      gene, and indicate differences in relative basal activity of the promoter
      regions.

PMID- 18096930
TI  - Growth hormone can induce expression of four major milk protein genes in
      transfected MAC-T cells.
AB  - Growth hormone (GH) can increase milk production in cattle, and this effect was
      thought to be mediated by an indirect mechanism because traditional ligand
      binding assays failed to detect GH binding sites in the mammary gland. However,
      recent findings that GH receptor (GHR) mRNA and protein are expressed in the
      epithelial cells of the bovine mammary gland suggest that GH may directly act on
      these cells to affect milk production. Therefore, the objective of this study was
      to determine whether GH could affect milk protein gene expression, nutrient
      uptake, and cell proliferation in bovine mammary epithelial cells using the
      bovine mammary epithelial cell-derived MAC-T cells as a model. Native MAC-T cells
      had low expression of GHR. Thus, we transfected them with expression plasmids for
      GHR and signal transducer and activator of transcription 5 (STAT5), 2 key
      components of GHR signaling, to maximize their GH response. Growth hormone
      increased the expression of alphaS1-casein, alphaS2-casein, beta-casein, and
      alpha-lactalbumin mRNA 16- to 117-fold in the transfected MAC-T cells, whereas it
      had no effect on the expression of kappa-casein, beta-lactoglobulin, or insulin
      like growth factor I mRNA. Cotransfection analyses showed that GH also strongly
      induced reporter gene expression from alphaS1-casein, alphaS2-casein, beta
      casein, and alpha-lactalbumin gene promoters. Growth hormone had no effect on the
      uptake of 2-deoxyglucose, an unmetabolizable glucose analog, amino acids, or
      oleic acid; neither did it affect cell proliferation or death. These observations
      together with the fact that GH receptor mRNA and protein are expressed in the
      epithelial cells of the bovine mammary gland raise the possibility that GH might
      act directly on the mammary epithelial cells in cows to stimulate transcription
      of major milk protein genes, as part of the mechanism by which GH stimulates milk
      production.

PMID- 18096931
TI  - Association between the presence of antibodies to Mycobacterium avium subspecies
      paratuberculosis and somatic cell count.
AB  - Somatic cell counts (SCC) in bulk tank milk delivered for human consumption are
      one of the indicators of milk quality and are used for milk pricing.
      Consequently, milk from cows with high SCC is frequently used by farmers for
      feeding of calves to lower the SCC in bulk tank milk. Young calves are more
      susceptible to Mycobacterium avium ssp. paratuberculosis (MAP) and may acquire
      the infection early in life through ingestion of MAP-contaminated milk. The
      occurrence of MAP antibodies can be an indicator of MAP shedding. Because MAP can
      be shed in milk from infected cows, and antibodies to MAP can be an indicator of
      the infectious status, an association between antibodies to MAP and high SCC can
      result in high-SCC milk being at risk of containing MAP. Feeding milk containing
      high SCC to susceptible calves may result in MAP infections. Somatic cell counts
      and MAP antibodies in milk were measured repeatedly in 7,251 cows from 26 Danish
      dairy herds to investigate the association between the occurrence of MAP
      antibodies and high SCC. The results of robust regression showed a log-linear
      relationship between the age at first positive ELISA and the age at first high
      SCC sample (R2 = 0.51). Of the 1,733 cows positive for MAP antibodies and with
      high SCC, high SCC was detected prior to MAP antibodies in 46% of the cows.
      Still, in 40% of the cows, MAP antibodies were detected before a high SCC.
      Therefore, the findings do not point to a causal relationship between high SCC
      and antibodies to MAP, but suggest a strong association and highlight a
      potentially increased risk of MAP transmission when milk with high SCC is fed to
      calves.

PMID- 18096932
TI  - Evaluation of a lameness scoring system for dairy cows.
AB  - Lameness is a major problem in dairy production both in terms of reduced
      production and compromised animal welfare. A 5-point lameness scoring system was
      developed based on previously published systems, but optimized for use under
      field conditions. The scoring system included the words "in most cases" in the
      descriptions of the clinical signs evaluated. This was done to avoid a situation
      in which cows might not fit into any of the categories. Additionally, a number of
      clinical signs used in other lameness scoring systems, considered of less
      importance in relation to lameness, were not included. Only clinical signs were
      included that could easily be assessed within a few seconds from a distance. The
      scoring system was evaluated with intra-and interobserver agreement using kappa
      statistics. The evaluation was done before and after training 5 observers.
      Weighted kappa values ranged from 0.38 to 0.78 for intraobserver agreement, with
      mean kappa values across all observers of 0.60 and 0.53 before and after
      training, respectively. Weighted kappa values ranged from 0.24 to 0.68 for
      interobserver agreement, with mean kappa values across all pairs of observers of
      0.48 and 0.52 before and after training, respectively. Training had only a
      limited positive effect on intra- and interobserver agreement. Additionally, how
      the different lameness categories are distributed along a theoretical scale
      representing the full spectrum of lameness from "absolutely normal gait" to "as
      lame as a cow can possibly be" was evaluated. This evaluation was done using the
      polychoric correlation coefficient. The estimated within-observer polychoric
      correlation coefficient ranged from 0.76 to 0.96, and there were no significant
      differences between the thresholds used to classify cows into different lameness
      categories by different observers before or after training. In conclusion, the
      results suggest that the lameness categories were not equidistant and the scoring
      system has reasonable reliability in terms of intra- and interobserver agreement.

PMID- 18096933
TI  - 17Beta-estradiol and estrone concentrations in plasma and milk during bovine
      pregnancy.
AB  - Estrone (E1) and 17beta-estradiol (E2) are present in milk, but the mechanism(s)
      that regulate their appearance in milk are not known. The objectives of this
      study were to determine the impact of stage of pregnancy on the concentrations of
      E1 and E2 in plasma and milk and to determine the correlations between plasma and
      milk E1 and E2 and with milk components throughout pregnancy. Blood and milk
      samples were collected from 13 cows every 28 d throughout pregnancy. The E1 and
      E2 were quantified in plasma and milk using RIA after organic solvent extractions
      and Sephadex LH-20 column chromatography. Plasma E1 concentrations averaged 0.8,
      16.9, and 41.8 pg/mL in trimesters 1, 2, and 3, respectively. The respective E1
      concentrations in milk averaged 0.6, 7.9, and 27.1 pg/mL. The E2 concentrations
      in plasma averaged 0.5, 0.9, and 2.0 pg/mL; milk E2 averaged 0.3, 0.9, and 5.0
      pg/mL. Plasma and milk E2 concentrations were greater in trimester 3 compared
      with trimesters 1 and 2. The E1 concentrations in milk were significantly
      correlated with plasma E1 concentrations (r = 0.77), percentage of milk fat (r =
      0.50), and milk yield (r = -0.43). The E2 concentrations in milk were
      significantly correlated with plasma E2 concentrations (r = 0.93), percentage of
      milk protein (r = 0.63), and milk yield (r = -0.57). The milk-to-plasma ratio of
      E2 increased from 0.4 during trimester 1 to 2.2 in trimester 3, which suggested
      that the mechanism(s) regulating the appearance of E2 in milk may change over the
      course of pregnancy.

PMID- 18096934
TI  - Short communication: Outbreak of Nocardia neocaledoniensis mastitis in an Italian
      dairy herd.
AB  - Nocardia spp. are an uncommon cause of mastitis, and outbreaks have typically
      been reported in dairy farms with poor hygienic and management conditions. The
      outbreak described herein involved a dairy farm with 43 lactating cows that,
      after a long period with low bulk milk somatic cell counts (<180,000 cells/mL),
      experienced an increasing incidence of clinical mastitis with bulk milk somatic
      cell counts greater than 300,000 cells/mL. Fifteen mastitic quarters milk samples
      from 9 dairy cows were found to be infected by a member of the genus Nocardia, as
      identified on the basis of selected phenotypic and chemotaxonomic
      characteristics. The isolates were confirmed as Nocardia neocaledoniensis by 16S
      rDNA gene sequencing. Average quarter milk somatic cell count for infected udders
      was 863,057 cells/mL, significantly greater than the average value in noninfected
      quarters (189,710 cells/mL).

PMID- 18096935
TI  - Uterine and hepatic gene expression in relation to days postpartum, estrus, and
      pregnancy in postpartum dairy cows.
AB  - The somatotropic axis consisting of growth hormone, the growth hormone receptor
      (GHR) insulin-like growth factor (IGF)-I, and IGF binding proteins changes with
      the stage of lactation and nutrition of the cow and may be 1 mechanism through
      which lactation and nutrition affect the establishment of pregnancy. The
      objective of this study was to quantify GHR, IGF-I, and IGF binding protein-2
      (IGFBP-2) mRNA in liver and uterine endometrial tissue at 4 stages of lactation
      (40, 80, 120, and 160 days in milk) and around the time of artificial
      insemination. Estrus was synchronized with GnRH and PGF2alpha, and cows were
      inseminated 12 h after estrus. Uterine biopsies were collected immediately before
      the second injection of PGF2alpha (before estrus), at the initiation of standing
      estrus, and 4 d after estrus. Liver biopsies were collected once on 4 d after
      estrus. The abundance of GHR, IGF-I, and IGFBP-2 mRNA in liver and uterus was
      determined by real-time quantitative PCR. The amount of liver IGF-I mRNA was
      positively correlated with plasma IGF-I concentrations. Cows that became pregnant
      after AI had more GHR and IGFBP-2 mRNA in their liver than cows that did not
      become pregnant. There was no effect of DIM or pregnancy status on abundance of
      uterine mRNA; however, uterine GHR and IGF-I mRNA was most abundant at estrus. In
      summary, cows at different stages of lactation or with different pregnancy
      statuses had similar quantities of uterine mRNA. In contrast, liver quantities of
      mRNA differed relative to pregnancy status. These data provide evidence that
      liver indices of metabolic state may be indicative of pregnancy success.

PMID- 18096936
TI  - Ability of organic and inorganic bedding materials to promote growth of
      environmental bacteria.
AB  - The major objective of this study was to contrast the ability of 4 commonly
      utilized bedding materials to promote growth of environmental bacteria under
      controlled conditions. A second objective was to describe the relationship
      between bacterial growth and specific biochemical or nutritional properties of
      these bedding materials. Unused samples of clean sand (CS; n = 20), recycled sand
      (RS; n = 21), digested manure solids (DS; n = 15), and shavings (SH; n = 15) were
      collected from bedding storage areas on 49 commercial Minnesota and Wisconsin
      dairy farms. Sterilized bedding samples were inoculated with Klebsiella
      pneumoniae and Enterococcus faecium then incubated, in triplicate, for 72 h at 37
      degrees C. Subsamples were collected after 0, 24, 48, and 72 h of incubation for
      culture and enumeration of bacteria. Subsamples of bedding were also tested for
      pH, total C content (%), and total N content (%). If bacterial growth occurred,
      peak levels were typically achieved within 24 h. Digested manure solids promoted
      the greatest amounts of growth of K. pneumoniae, followed by RS and then SH,
      whereas CS promoted the least. There would seem to be a tradeoff in selecting SH
      as a bedding material, because it supported moderate growth of K. pneumoniae but
      caused a rapid decline in the numbers of E. faecium. However, RS, CS, and DS each
      only supported relatively small amounts of growth of E. faecium, so the benefit
      of SH relative to other bedding materials is limited. High bedding pH may
      partially explain why some bedding materials supported growth of E. faecium
      (e.g., DS and RS). Both high bedding pH (e.g., as for DS or RS) and high total C
      (%) content (e.g., as for DS and SH) may partially explain why some bedding
      materials supported growth of K. pneumoniae.

PMID- 18096937
TI  - Measuring concentrations of insulin-like growth factor-I with an enzyme-linked
      immunosorbent antibody assay in plasma samples from Holstein cows.
AB  - This study describes the use of a commercial nonextraction ELISA to quantify
      total concentrations of insulin-like growth factor-I (IGF-I) in plasma samples
      from Holstein cows fed pasture-based diets varying in dry matter and
      metabolizable energy density. The assays were conducted using the protocols
      provided by the manufacturer. The ELISA was verified for linearity, accuracy in
      measuring IGF-I from spiked plasma samples, and precision involving variation
      within and between assays. Validation also involved comparing results of the
      ELISA against an established RIA after defatted plasma samples were subjected to
      acid gel HPLC to dissociate and separate IGF and IGF binding protein complexes.
      Validation results had low coefficients of variation (CV; intraassay CV of less
      than 6% and interassay CV of less than 8%) and a high recovery percentage of IGF
      I (79%) from samples spiked with unbound IGF-I. The coefficients of determination
      between the ELISA and the RIA reference assay were 0.90 in 2 separate assays.
      Associations between the RIA and the ELISA were higher, and the limits of
      agreement at 95% confidence intervals were narrower compared with those between
      the RIA and a modified ELISA procedure in which IGF binding protein complexes
      were extracted using HPLC. The samples were obtained from cows sampled over a
      period of 5 wk. These results demonstrated that the DSL-10-2800 nonextraction IGF
      I ELISA was acceptably specific and sufficiently sensitive to be used to measure
      the extent and patterns of change in the plasma concentrations of IGF-I in
      samples from lactating Holstein cows.

PMID- 18096939
TI  - The effect of concrete floor roughness on bovine claws using finite element
      analysis.
AB  - The interaction between bovine claws and a concrete floor with defined roughness
      and friction coefficients is described using a finite element model. The model
      was built by using x-ray tomography scanner images of an unloaded fore and hind
      bovine claw. These images were used to reproduce the geometry of the claw horn
      capsule, which was used to create a finite element model. Young's moduli of 382,
      261, and 13.6 MPa were attributed to the dorsal wall horn, abaxial and axial wall
      horn, and bulb horn, respectively. Poisson's ratio was set at 0.38. The horn was
      considered an isotropic elastic material. The model was completed by introducing
      a rigid support that simulated a concrete floor. The floor was moved to establish
      contact with the claw and was loaded with a force of 2 or 6 kN. The top border
      area of the horn capsule was fixed, but angular rotations were allowed. With this
      model, the effect of varying floor roughness and claw-floor friction on contact
      pressures and von Mises stresses in the claw horn could be evaluated. This was
      demonstrated by simulating the contact between the claw models and a smooth and
      rough floor with a center-line roughness value R(a) of 0 or 0.175 mm,
      respectively, either without friction or with a static coefficient of friction of
      0.75 and a dynamic coefficient of friction of 0.65. Contact pressures ranged from
      2.14 to 27.55 MPa. The roughness of the floor was the main determinant in
      subsequent contact pressures. Maximum von Mises stresses were registered in the
      claw sole and were mostly between 5.04 and 16.44 MPa, but could be higher in
      specific situations. The variables claw (fore or hind) and floor (smooth or
      rough) had significant effects on the contact pressures; in addition, the floor
      resulted in significantly different von Mises stresses in the claw horn. The
      variable friction (frictionless or with friction) had a significant effect on the
      von Mises stresses. The load did not result in significantly different contact
      pressures and von Mises stresses because of the large increase in contact area
      with the exerted load.

PMID- 18096938
TI  - Quarter-level analysis of subclinical and clinical mastitis in primiparous
      heifers following the use of a teat sealant or an injectable antibiotic, or both,
      precalving.
AB  - This study investigated the effect of infusion of a bismuth subnitrate teat canal
      sealant or an injectable antibiotic, or both, in heifers on the cure of existing
      intramammary infection (IMI), incidence of new IMI, prevalence of postcalving
      IMI, and incidence of clinical mastitis in the first 2 wk postcalving at the
      quarter level. Heifers (n = 1,067) in 30 seasonally calving, pasture-fed dairy
      herds were randomly assigned at the heifer level to 1 of 4 treatments (no
      treatment; 3 intramuscular injections of 5 g of tylosin antibiotic at 24-h
      intervals; infusion of a teat sealant into all 4 quarters; 3 intramuscular
      injections of 5 g of tylosin antibiotic and infusion of teat sealant into all 4
      quarters). Mammary gland secretion samples were collected from each quarter of
      every heifer before treatment. Heifers within a herd were enrolled on one
      calendar day, 27 d (on average) before the planned start of the seasonal calving
      period. Duplicate milk samples were collected from each gland within 5 d after
      calving for bacterial culture and from glands the herdowners diagnosed as having
      clinical mastitis. The relative risk of effect of treatment on the incidence of
      cure, incidence of new IMI, prevalence of postcalving IMI, and incidence of
      clinical mastitis were calculated at the gland level using multivariate logistic
      regression analyses. Neither infusion of a teat sealant nor treatment with the
      injectable antibiotic increased the cure of precalving IMI. Infusion of the teat
      sealant reduced the risk of new IMI with any pathogen by 74%, reduced the
      prevalence of postcalving IMI by 65%, reduced the risk of new infection with
      Streptococcus uberis by 70% in quarters with an IMI precalving, and reduced the
      incidence of clinical mastitis from which a pathogen was isolated by 70% in
      quarters with an IMI precalving. Parenteral antibiotic treatment had no effect on
      any of these outcomes. In conclusion, use of an internal teat-canal sealant in
      heifers reduced the postcalving IMI prevalence and the incidence of pathogen
      associated clinical mastitis postcalving by decreasing the incidence of new
      infections over this high-risk peripartum period, and may be a useful tool for
      reducing the risk of mastitis in heifers.

PMID- 18096940
TI  - Increase in Escherichia coli inoculum dose accelerates CD8+ T-cell trafficking in
      the primiparous bovine mammary gland.
AB  - Although migration of leukocytes into the mammary gland is pivotal for a cow's
      response against intramammary invading pathogens, the contribution of lymphocyte
      subsets to this response remains unclear. To investigate the dynamics of
      lymphocyte populations during Escherichia coli mastitis, T-lymphocyte subsets,
      CD4+/CD8+ ratio, CD21+ cells, and lymphoproliferation were studied in blood and
      milk of primiparous cows exposed to different quantities of bacteria. The cows
      were intramammarily inoculated with 10(4) cfu of E. coli (group A) and 10(6) cfu
      (group B). Compared with group A, a much greater number of lymphocytes migrated
      into the infected quarters at postinfection hour (PIH) 6 to 24 in group B, and
      the CD8+ cells were the first-recruited T cells in the milk. There was a
      significant decline in the CD4+/CD8+ ratios at PIH 6 to 24 in group B. The
      decrease of CD4+/CD8+ ratios at PIH 6 to 24 resulted mainly from greater CD8+
      cell concentrations in milk. In contrast, at PIH 72, CD4+/CD8+ ratios increased
      about 2-fold in both groups. This increase was mainly due to the increase in CD4+
      cell concentration. The increased concentration of CD4+ cells coincided with an
      increase in the CD21+ cell population in the milk. In blood, the increase of CD8+
      cells appeared much faster in group B (PIH 6 and 12) than in group A. The results
      from lymphoproliferation also indicated a greater increase in the proliferative
      response in both blood and milk lymphocytes of group B. Our study demonstrates
      for the first time that an increase of E. coli inoculum dose accelerates the
      trafficking of CD8+ cells during initiation of E. coli mastitis, and these cells
      are the predominant T cells in milk during the early hours of bovine E. coli
      mastitis.

PMID- 18096941
TI  - Ruminal temperature may aid in the detection of subacute ruminal acidosis.
AB  - The objective of this study was to investigate the relationship between ruminal
      pH and ruminal temperature and to develop a predictive equation that can aid in
      the diagnosis of subacute ruminal acidosis (SARA). Six rumen-fistulated lactating
      Holstein dairy cows (639 +/- 51 kg body weight) were used in the study. Cows were
      randomly allocated to 1 of 2 dietary treatments: control (% of dry matter, 40%
      corn silage, 27% mixed haylage, 7% alfalfa hay, 18% protein supplement, 4% ground
      corn, and 4% wheat bran) or SARA total mixed ration (% of dry matter, 31% corn
      silage, 20% mixed haylage, 5% alfalfa hay, 15% protein supplement, 19% ground
      wheat, and 10% ground barley) and were fed daily at 0700 and 1300 h. The
      experiment consisted of 1 wk of adaptation followed by 1 wk of treatment. Ruminal
      pH and ruminal temperature were simultaneously and continuously recorded every
      minute for 4 d per week using the same indwelling electrode. Subacute-acidotic
      cows spent more time (min/d) below ruminal pH 5.6 and a greater time above 39.2
      degrees C than control cows. Ruminal pH nadir had a negative relationship with
      its corresponding ruminal temperature (R2 = 0.77). Therefore, ruminal temperature
      may have potential to predict ruminal pH and thus aid in the diagnosis of SARA.

PMID- 18096942
TI  - Metabolic changes and net portal flux in dairy cows fed a ration containing rumen
      protected fat as compared to a control diet.
AB  - Feeding rumen-protected fat (RPF) is an alternative to increase energy density of
      the diet and therefore energy intake in dairy cows. To investigate metabolic and
      endocrine changes in dairy cows fed either a diet containing RPF (FD) or a
      control diet with an increased amount of cornstarch (SD), 3 Holstein cows (83 +/-
      1 d in milk) were fitted with catheters in the portal vein, a mesenteric artery,
      and 2 mesenteric veins. Cows were fed consecutively SD and FD for 3 wk,
      respectively. In FD, cornstarch [92 g/kg of dry matter (DM)] was replaced by 50 g
      of RPF/kg of DM (mainly C16:0 and C18:1). Tracer infusions of NaH(13)CO3 and D-[U
      (13)C6]glucose were performed into a jugular vein to measure rate of appearance
      and oxidation of glucose. Arterial and portal blood samples were collected to
      measure concentrations of glucose, lactate, volatile fatty acids, nonesterified
      fatty acids, beta-hydroxybutyrate, triglycerides, AA, insulin, and glucagon.
      Concomitantly, para-aminohippurate was infused into a mesenteric vein for
      measurement of portal plasma flow. Although DM intake was slightly lower in FD,
      protein and energy intakes were unaffected by diets. Milk and lactose yields were
      higher in FD than SD. Arterial plasma glucose concentration was lower with FD
      than SD, whereas nonesterified fatty acid and triglyceride concentrations were
      higher in FD. Glucagon concentration and glucagon-to-insulin ratio were both
      augmented by FD feeding. When feeding FD, greater milk and lactose yields, but
      not energy-corrected milk, were associated with elevated lipid status and higher
      glucagon concentrations but occurred despite lower plasma glucose concentration
      and were not linked with changes in whole body glucose rate of appearance. This
      study suggests a glucose-sparing effect allowing an enhanced lactose synthesis
      when feeding RPF.

PMID- 18096943
TI  - Milk synthetic response of the bovine mammary gland to an increase in the local
      concentration of amino acids and acetate.
AB  - Rates of secretion of components into milk are a function of precursor
      concentrations and parameters that describe expression of the milk synthetic
      enzymes and their sensitivity to precursor concentrations. To establish the
      enzymatic sensitivities of milk fat yield and mammary acetate utilization to
      circulating acetate concentration, lactating cows were infused for 10 h with 0 or
      40 g of acetate/h in an external iliac artery supplying one udder half. In
      addition, to investigate the possibility that energy supply influences the milk
      protein response to an elevated amino acid (AA) concentration, 2 different AA
      profiles were infused with and without acetate. Six cows, fed a total mixed
      ration of 21% crude protein ad libitum, were infused with AA at 0 g/h, 30 g/h in
      the profile of rumen microbes, or 30 g/h in the profile of milk proteins, in a 3
      x 2 factorial arrangement with the 2 acetate treatments of 0 and 40 g/h, all in a
      6 x 6 Latin square. Amino acid infusion caused a 60% increase, on average, in
      plasma concentration of AA entering the infused udder half. From the microbial AA
      profile, 49% of infused AA were taken up by the udder half, 42% of which occurred
      during the first pass. From the milk AA profile, 44% of infused AA were taken up
      by the udder half, 50% of which occurred during the first pass. There was an 8%
      increase in yield of milk protein with AA infusion, representing 7% capture, but
      no effect of the infused profile. Acetate infusion caused a decrease in the
      yields of milk protein and lactose when AA were infused, but not when AA were
      absent. Milk fat yields were not affected, although acetate concentrations in
      plasma entering the infused udder half increased by 123% and mammary uptakes
      increased by 128%. Mammary uptakes of long-chain fatty acids and beta
      hydroxybutyrate were not affected by acetate infusion, whereas glucose uptakes
      tended to increase. It was suggested that excess acetate may have been
      sequestered in adipose tissue in the udder. Yields of both protein and fat in
      milk showed a low sensitivity to the concentration of their precursors in
      circulation. It was concluded that the Km in Michaelis-Menten-type equations
      describing milk synthesis should be assigned a low value, and that the Vmax is
      regulated to bring about changes in milk yield and composition.

PMID- 18096944
TI  - Effects of feeding forage soybean silage on milk production, nutrient digestion,
      and ruminal fermentation of lactating dairy cows.
AB  - The objective of this study was to determine the feeding value of forage soybean
      silage (SS) for dairy cows relative to a fourth-cut alfalfa silage (AS). Forage
      soybean was harvested at full pod stage. Two isonitrogenous diets were formulated
      with a 48:52 forage:concentrate ratio. Soybean silage and AS constituted 72% of
      the forage in each diet, with corn silage constituting the remaining 28%. Twenty
      Holsteins cows in early lactation were used in a switchback design. Four
      lactating Holsteins cows fitted with ruminal cannulas were used to determine the
      effects of dietary treatments on ruminal fermentation parameters and in vivo
      total tract nutrient utilization. Relative to AS, SS contained 15, 28, and 25%
      more neutral detergent fiber, acid detergent fiber, and crude protein,
      respectively. Dry matter intake (23.5 vs. 25.1 kg/d) and milk yield (35.5 vs.
      37.2 kg/d) were lower for cows fed SS than for those fed AS. However, energy
      corrected milk and milk efficiency were similar for both dietary treatments. Milk
      protein, lactose, and total solids concentrations were not influenced by dietary
      treatments (average 3.0, 4.7, and 12.6%, respectively). However, cows fed SS
      produced milk with greater milk fat (3.8 vs. 3.6%) and milk urea nitrogen
      concentrations (15.6 vs. 14.3 mg/dL) compared with cows fed AS. Ruminal pH was
      lower, whereas ruminal NH3-N concentration was greater in cows fed SS than in
      cows fed AS. Total tract digestibilities of dry matter, crude protein, and
      neutral detergent fiber were not influenced by silage type. We concluded that
      forage SS, when compared with AS, had a negative impact on feed intake and milk
      yield, whereas energy-corrected milk, milk efficiency, and total tract nutrient
      digestion were similar.

PMID- 18096945
TI  - Short communication: The effect of water temperature on the viability of silage
      inoculants.
AB  - The objective of this study was to determine if exposure to high temperatures in
      water affects the viability of various silage inoculants. Inoculants were
      enumerated on De Man, Rogosa, Sharpe agar to standardize a final count (colony
      forming units) in water such that about 500 mL added to 1 tonne of wet forage
      would achieve a recommended application rate of about 100,000 cfu of lactic acid
      bacteria (LAB) per gram of wet forage. Testing was done in 4 sequences (SEQ). For
      each SEQ, inoculants were mixed in deionized water for 45 min at 30 degrees C
      followed by incubation for 6 h at 30 degrees C (SEQ 1), 35 degrees C (SEQ 2), 40
      degrees C (SEQ 3), or 45 degrees C (SEQ 4) in duplicate 125-mL flasks rotating at
      125 rpm. After 6 h, rotation was stopped and the temperature was lowered to 30
      degrees C for the next 18 h for all SEQ. Numbers of LAB were enumerated at 0, 3,
      6, and 24 h. Each sequence was repeated twice. Incubation at a moderate
      temperature (SEQ 1) did not affect the viability of the microbial inoculants. The
      viability of the inoculants declined with increasing temperature (SEQ 2 to 4) but
      the effect varied by inoculant. For some inoculants exposure to 35 degrees C
      resulted in substantial decreases in viable cells (loss of 0.5 to 1 log cfu/mL).
      Incubation at higher temperatures resulted in even greater losses in viability
      for some inoculants. Losses of more than 0.5 log cfu/mL would most likely make
      the application of these inoculants ineffective in the field. Lactobacillus
      plantarum MTD/1 was the most thermotolerant organism tested, because it was
      unaffected by all temperatures (30 to 45 degrees C) after 3 h of incubation.
      Lactobacillus plantarum MTD/1 and Lactobacillus buchneri 40788 also appeared to
      have better thermotolerance as their numbers substantially increased between 6
      and 24 h in SEQ 4. These data show that some silage inoculants are more
      thermotolerant than others and that precautions should be taken to ensure that
      microbial inoculants that are applied to forage do not reach elevated
      temperatures during use.

PMID- 18096946
TI  - Phosphorus utilization and environmental and economic implications of reducing
      phosphorus pollution from Ontario dairy cows.
AB  - A major source of environmental pollution has been overfeeding P to dairy cows,
      caused by the "safety margins" added to diets in order not to compromise the
      health and production of animals. An extant whole-animal model was evaluated
      using an experiment conducted in Ontario to assess its applicability for
      predicting P excretion. The objective of the study was to use the model to
      estimate P excretion levels and the economic and environmental implications of
      implementing mitigating options by following recommendations from studies that
      have reported sufficient levels of P inclusion in the diet. Mean square
      prediction error and concordance coefficient analysis showed that the overall
      predictions were close to the mean and that there was only a slight
      underprediction of fecal P output by the model. The majority of the error was
      random, with only 8.9% coming from error caused by deviation from the regression
      line, and the model did not show a systematic trend of over- or underprediction.
      The model was then used to predict P excretion in Ontario by using diets commonly
      fed to dairy cows on Ontario farms. It is estimated that Ontario dairy farms
      produce 7 kt of P annually at current levels of P inclusion in the diet. Reducing
      P levels from the current 0.41% P of dry matter to 0.35% is estimated to save
      producers CAN $20/cow per year and the environment 1.3 kt/yr without impairing
      cow health or productivity. Additionally, the reductions might be from inorganic
      P sources added to the feed, which are more polluting than organic sources
      because of their water-soluble nature and liability to leaching and runoff.

PMID- 18096947
TI  - Interactions between barley grain processing and source of supplemental dietary
      fat on nitrogen metabolism and urea-nitrogen recycling in dairy cows.
AB  - The objective of this study was to determine the effects of methods of barley
      grain processing and source of supplemental fat on urea-N transfer to the
      gastrointestinal tract (GIT) and the utilization of this recycled urea-N in
      lactating dairy cows. Four ruminally cannulated Holstein cows (656.3 +/- 27.7 kg
      of BW; 79.8 +/- 12.3 d in milk) were used in a 4 x 4 Latin square design with 28
      d periods and a 2 x 2 factorial arrangement of dietary treatments. Experimental
      diets contained dry-rolled barley or pelleted barley in combination with whole
      canola or whole flaxseed as supplemental fat sources. Nitrogen balance was
      measured from d 15 to 19, with concurrent measurements of urea-N kinetics using
      continuous intrajugular infusions of [15N 15N]-urea. Dry matter intake and N
      intake were higher in cows fed dry-rolled barley compared with those fed pelleted
      barley. Nitrogen retention was not affected by diet, but fecal N excretion was
      higher in cows fed dry-rolled barley than in those fed pelleted barley. Actual
      and energy-corrected milk yield were not affected by diet. Milk fat content and
      milk fat yield were higher in cows fed dry-rolled barley compared with those fed
      pelleted barley. Source of supplemental fat did not affect urea-N kinetics. Urea
      N production was higher (442.2 vs. 334.3 g of N/d), and urea-N entering the GIT
      tended to be higher (272.9 vs. 202.0 g of N/d), in cows fed dry-rolled barley
      compared with those fed pelleted barley. The amount of urea-N entry into the GIT
      that was returned to the ornithine cycle was higher (204.1 vs. 159.5 g of N/d) in
      cows fed dry-rolled barley than in pelleted barley-fed cows. The amount of urea-N
      recycled to the GIT and used for anabolic purposes, and the amounts lost in the
      urine or feces were not affected by dietary treatment. Microbial nonammonia N
      supply, estimated using total urinary excretion of purine derivatives, was not
      affected by diet. These results show that even though barley grain processing
      altered urea-N entry into the GIT, the utilization of this recycled urea-N for
      microbial production was unaffected as the additional urea-N, which entered the
      GIT was returned to ureagenesis.

PMID- 18096948
TI  - Response of milk fatty acid composition to dietary supplementation of soy oil,
      conjugated linoleic acid, or both.
AB  - Thirty-six Holstein cows were blocked by parity and allotted by stage of
      lactation to 6 treatments to evaluate the effects of dietary soy oil, conjugated
      linoleic acid (CLA; free acid or calcium salt), or both, on CLA content of milk.
      Diets were fed for 4 wk and are as follows: (1) control, (2) control + 5% soy
      oil, (3) control + 1% CLA, (4) control + 1% Ca(CLA)2, (5) control + 1% CLA + 4%
      soy oil, and (6) control + 1% Ca(CLA)2 + 4% soy oil. Rumen volatile fatty acid
      concentrations, blood fatty acid concentrations, milk yield, and milk composition
      were measured weekly or biweekly. Dry matter intake and milk yield were recorded
      daily. Dietary supplementation of soy oil or CLA had no effect on daily milk
      yield, milk protein concentration and production, or milk lactose concentration
      and production. Supplementation of unsaturated fatty acids as soy oil, CLA, or
      Ca(CLA)2 increased total fatty acid concentration in plasma, decreased milk fat
      concentration and production, and had no effect on rumen volatile fatty acid
      concentrations. The weight percentage of CLA in milk was increased from 0.4 to
      0.7% with supplementation of 1% CLA, to 1.2% with supplementation of soy oil, and
      to 1.3% with supplementation of 1% CLA plus soy oil. Supplementation with
      Ca(CLA)2 or Ca(CLA)2 + soy oil increased the CLA content of milk fat to 0.9 and
      1.4%, respectively. In summary, adding 5% soy oil was as effective as
      supplementing CLA, Ca(CLA)2, or a combination of 1% CLA (free acid or calcium
      salt) + 4% soy oil at increasing CLA concentrations in milk fat. Feeding CLA as
      the calcium salt resulted in greater concentrations of CLA in milk fat than did
      feeding CLA as the free acid. Dietary supplementation of 5% soy oil or 4% soy oil
      + 1% CLA as the free acid or the calcium salt increased the yield of CLA in milk.

PMID- 18096949
TI  - Quantitative prediction of magnesium absorption in dairy cows.
AB  - The objective of the current study was to predict magnesium (Mg) absorption in
      dairy cows based on data from our own studies and those of other investigators.
      Balance data from 15 independent studies with 68 different rations and 323 dairy
      cows or cow-periods were used. In 12 studies, grass feeds were the main source of
      roughage and in about one-half of the studies, MgO-supplemented rations were
      used. Out of the 68 rations, 14 rations contained supplemental K in the form of
      bicarbonate, and in 2 rations additional K was incorporated mainly in form of
      KCl. The K content of the rations ranged from 6.9 to 75.6 g/kg of dry matter (DM;
      mean 29.4 g/kg of DM). In most studies (10/15), dry, nonpregnant cows were used.
      For lactating animals, milk yield ranged from 4 to 22 kg/d (mean yield, 15 kg/d).
      All studies provided quantitative information with respect to feed intake (DM
      intake, Mg, and K) and total Mg excretion in feces. The mean dietary Mg content
      was 4.5 g/kg of DM and ranged from 0.45 to 17.3 g/kg of DM. On average, Mg
      absorption (% of intake) was 26.2% and ranged from 9.9 to 73.7%. The variation in
      Mg absorption was at least partly explained by the variation in dietary K
      concentrations. Magnesium absorption (% of intake) was significantly decreased by
      0.31 percentage units/g of K in the DM. To counteract the depressant effect of
      dietary K on Mg absorption, Mg intake must be increased by 4 g/d when the dietary
      K concentration increases by 10 g/kg of DM so that the amount of absorbed Mg is
      maintained.

PMID- 18096950
TI  - The feeding value of corn distillers solubles for lactating dairy cows.
AB  - Fifteen Holstein cows (10 multiparous and 5 primiparous) in early to mid
      lactation (79.3 +/- 9.2 d in milk) were used in a multiple 5 x 5 Latin square
      design with 4-wk periods to evaluate and compare the use of condensed corn
      distillers solubles (CCDS) and dried distillers grains with solubles (DDGS) in
      the total mixed ration. The forage portion of the diets was kept constant at
      27.5% corn silage and 27.5% alfalfa hay (dry matter basis). Diets were 1) 0%
      distillers grains products (control); 2) 18.5% DDGS; 3) 10% CCDS; 4) 20% CCDS;
      and 5) a combination diet of 18.5% DDGS with 10% CCDS. Diets 2 and 3 contained 2%
      fat from DDGS or CCDS, whereas diet 4 contained 4% fat from CCDS and diet 5
      contained 4% fat from the blend of DDGS and CCDS. The diets were balanced to
      provide 17% crude protein with variation in acid detergent fiber, neutral
      detergent fiber, and fat concentration. Dry matter intake (21.5 kg/d) was similar
      for all diets. Milk yield (33.8, 36.2, 35.5, 36.0, and 36.0 kg/d) tended to be
      greater for diets 2 to 5 than for diet 1, whereas yields of fat (1.04 kg/d),
      protein (1.02 kg/d), fat percentage (2.94), and protein percentage (2.98) were
      similar for all diets. Energy-corrected milk (32.2 kg/d) and feed efficiency
      (1.58 kg of energy-corrected milk/kg of dry matter intake) were similar for all
      diets. Milk urea nitrogen (15.0, 10.9, 11.1, 11.0, and 11.4 mg/dL) as well as
      blood urea nitrogen (15.6, 12.5, 14.6, 13.8, and 14.2 mg/dL) were decreased in
      diets 2 to 5 compared with diet 1. Milk concentrations of long-chain fatty acids
      as well as polyunsaturated fatty acids were greater and medium-chain fatty acid
      concentrations were lower for diets 2 to 5 compared with diet 1. Concentrations
      of cis-9, trans-11 conjugated linoleic acid (CLA; 0.33, 0.68, 0.51, 0.85, and
      1.07 g/100 g of fatty acids) as well as trans-10, cis-12 CLA (<0.01, 0.01, <0.01,
      0.02, and 0.02 g/100 g of fatty acids) were greater for diets 2 to 5 compared
      with diet 1. Molar proportions of ruminal acetate decreased and propionate
      increased for diets 2 to 5 compared with diet 1. The results showed that CCDS is
      as effective as DDGS in replacing soybean meal and corn grain in the total mixed
      ration.

PMID- 18096951
TI  - Evaluation of nitrogen utilization and the effects of monensin in dairy cows fed
      brown midrib corn silage.
AB  - Twenty midlactation Holstein cows (4 ruminally fistulated) averaging 101 +/- 34 d
      in milk and weighing 674 +/- 77 kg were used to compare rations with brown midrib
      corn silage (bm3) to rations with dual-purpose control silage (DP) on N
      utilization and milk production. The effect of monensin in these rations was also
      examined. Animals were assigned to one of five 4 x 4 Latin squares with
      treatments arranged in a 2 x 2 factorial. Cows were fed 1 of 4 treatments during
      each of the four 28-d periods. Treatments were 1) 0 mg/d monensin and bm3 corn
      silage, 2) 0 mg/d monensin and DP corn silage, 3) 300 mg/d monensin and bm3 corn
      silage, and 4) 300 mg/d monensin and DP corn silage. In vitro 30-h neutral
      detergent fiber (NDF) digestibility was greater for bm3 corn silage (61.0 vs.
      49.1 +/- 0.62). Dry matter intake (DMI) tended to be greater for cows consuming
      bm3 corn silage (21.3 vs. 20.2 kg/d). Neither hybrid nor monensin affected milk
      production, fat, or protein (37.7 kg, 3.60%, or 3.04%). Monensin tended to
      increase rumen pH (5.89 vs. 5.79 +/- 0.07) compared with the control treatment.
      In addition, bm3 corn silage resulted in a significant decrease in rumen pH (5.72
      vs. 5.98 +/- 0.07). Supplementing monensin had no effect on molar proportions of
      acetate, propionate, or butyrate. In contrast, an increase was observed in
      branched-chain volatile fatty acids. No treatment interactions were observed for
      rumen pH or molar proportion of propionate but monensin decreased the molar
      proportion of acetate and increased the molar proportion of butyrate when cattle
      consumed bm3 silage. Dry matter, N, and acid detergent fiber digestibility were
      lower for the bm3 ration, whereas NDF digestibility was not different between
      treatments. There was no effect of hybrid on microbial protein synthesis (1,140
      g/d) as estimated by urinary concentration of purine derivatives. Cows consuming
      bm3 excreted more fecal N than cows consuming DP (38.2 vs. 34.4% N intake);
      however, based on spot sampling, estimated urinary and manure N were not
      different between treatments (35.8 and 71.9% N intake). Monensin had no effect on
      DMI, digestibility of any nutrients, or N metabolism, and there were no hybrid by
      monensin interactions. Rations including bm3 corn silage tended to increase DMI
      but did not affect production. The reduction in the digestibility of some
      nutrients when cows consumed bm3 may have been caused by increased DMI and
      possible increased digestion in the lower gut. This increase in DMI appeared to
      also have negatively affected N digestibility but not NDF digestibility. This
      resulted in a greater amount of N excreted in feces but did not affect total mass
      of manure N.

PMID- 18096952
TI  - In vitro fermentation vessel type and method alter fiber digestibility estimates.
AB  - Selected vessel types and conditions used for in vitro fermentation were compared
      to evaluate their effects on determinations of neutral detergent fiber (NDF)
      digestibility (NDFD) in 2 replicate 48-h fermentations. Treatments included 50-mL
      polyethylene centrifuge tubes with gas-release valves (treatment 1); 50-mL
      polyethylene centrifuge tubes with continuous gassing with CO2 (treatment 2); 50
      mL polyethylene centrifuge tubes sealed, oriented horizontally, and shaken
      continuously parallel to the long axis of the tube, with manual gas release
      (treatment 3); 125-mL Erlenmeyer flasks with continuous gassing with CO2
      (treatment 4); and 125-mL serum vials sealed with stoppers and crimp seals with
      (treatment 5) or without (treatment 6) manual gas release. Goering and Van Soest
      medium and blended ruminal inoculum from 4 lactating cows were used. Substrates
      were alfalfa hay, corn silage, ryegrass hay, and soyhulls. Gas was released and
      measured in treatments 3 and 6 at 3.0, 5.5, 9.0, 11.5, 23.5, 29.5, and 47.5 h by
      using a syringe with a hypodermic needle. Vessels from each treatment were
      harvested at 0, 6, 12, 24, 30, and 48 h for NDF analysis, with NDFD calculated as
      1 - [(residual NDF, g - residual NDF in fermentation blank, g)/sample NDF, g].
      Medium pH did not decline below 6.3 for any treatment. Average values for NDFD
      for 24 through 48 h were 0.576, 0.639, 0.688, 0.668, 0.679, and 0.681 for
      treatments 1 through 6, respectively (standard error of the difference = 0.008).
      The lowest NDFD was noted for treatment 1, which differed from all other
      treatments; treatments 3, 4, 5, and 6 did not differ by treatment or by the
      interaction of treatment and substrate. Treatments 1 and 2 gave lower NDFD values
      than the other treatments, but these differences were not consistent and differed
      by substrate, with alfalfa showing the fewest differences among treatments and
      soyhulls the most. Net energy of lactation values for substrates, as predicted
      from differences in 48-h NDFD, were 7 to 15% lower for treatment 1 than for the
      average of all other treatments. Slopes of the gas production per gram of
      substrate dry matter curves differed between treatments 3 and 5. In conclusion,
      measured NDFD was altered by fermentation treatment, with polyethylene tubes +
      gas-release valves giving the lowest values. Consequently, NDFD values may not be
      comparable across fermentation methods, but the effect will vary among
      feedstuffs. The combination of methods used for sealing, gassing, or agitating
      vessels may have a greater impact on NDFD than does vessel type.

PMID- 18096953
TI  - The definition of acidosis in dairy herds predominantly fed on pasture and
      concentrates.
AB  - This cross-sectional survey examined the prevalence of ruminal acidosis and the
      effects of acidosis on the production of dairy cattle. Eight fresh cows, 3
      primiparous and 5 multiparous (< 100 d in milk), were selected randomly from each
      of 100 dairy herds in 5 regions of Australia. Rumen fluid was obtained from each
      cow by rumenocentesis and a stomach tube, and samples were tested for pH. Stomach
      tube rumen fluid samples were analyzed for volatile fatty acid, ammonia, and D
      lactate concentrations. On the basis of the results of all assays, cows were
      categorized into 3 distinct categories (categories 1, 2, and 3) by cluster
      analysis. The percentages of cattle in categories 1, 2, and 3 were 10.2, 29.9,
      and 59.9%, respectively. Mean rumen pH for categories 1, 2, and 3 were 5.74 +/-
      0.47, 6.18 +/- 0.44, and 6.33 +/- 0.43, respectively. Biochemically, categories
      1, 2, and 3 were characterized, respectively, as follows: mean total VFA
      concentration (mM), 100.74 +/- 23.22, 94.79 +/- 18.13, and 62.81 +/- 15.65; mean
      ammonia concentration (mM), 2.46 +/- 2.02, 7.79 +/- 3.75, and 3.64 +/- 2.03; and
      mean D-lactate concentration (mM), 0.34 +/- 0.86, 0.28 +/- 0.97, and 0.12 +/-
      0.51. Category 1 cows had higher propionate, valerate, isovalerate, and caproate
      concentrations and were of lower parity than cows in other categories. Cows in
      category 1 had higher milk production but lower milk fat content than category 2
      cows. Herds were assigned to 1 of 3 groups according to the numbers of cows
      assigned to each category. Herds with > or = 3 of the 8 cows in category 1 were
      classified as acidotic. Herds with > or = 3 of the 8 cows in category 2 were
      classified as having suboptimal rumen function, and herds with > or = 3 of the 8
      cows in category 3 were classified as normal. Herds that had 3 or more of the 8
      cows in category 1 (acidotic herds) had diets with higher energy and nonfiber
      carbohydrate contents and a lower neutral detergent fiber content than herds with
      a high prevalence of category 2 or 3 cows. The lack of significance of a herd
      effect in the statistical models developed suggests that the categories were
      robust across production systems, in which diets varied from all pasture to total
      mixed rations. A point prevalence of 10% (95% credible interval, 8 to 12%) of
      cows with an acidotic profile indicates a high risk for acidosis in the cattle
      sampled. The higher nonfiber carbohydrate and lower neutral detergent fiber
      contents of diets for herds with a high prevalence of category 1 cows (acidotic
      herds) indicates that there may be opportunities to reduce the risk of acidosis
      by dietary manipulation.

PMID- 18096954
TI  - Genetic analysis of locomotion and associated conformation traits of Holstein
      Friesian dairy cows managed in different housing systems.
AB  - The objectives of this study were to determine the influence of housing on
      lameness-related linear and composite traits, and to estimate heritabilities of
      the traits and correlations among them. Data comprised 156,770 national type
      evaluation records of pedigreed first-lactation Holstein-Friesian cows that
      calved from 2000 through 2006 and were classified in different housing systems-
      cubicles, straw yards, slatted or loafing yards, and on pasture. Locomotion score
      (LOCO), rear leg, side view (RLS), foot angle (FA), bone quality (BO-NEQ), legs
      and feet (L&F), and mammary composite (MAMM) were the traits measured. Data were
      analyzed by REML, using an animal model. In general, cows in grazing systems had
      better locomotion, straighter RLS, steeper FA, flat and more refined bones,
      better L&F, and better mammary systems compared with cows housed in other
      systems. Estimates of heritability ranged from 0.11 for LOCO to 0.31 for MAMM.
      Bone quality had the highest heritability (0.23) of the traits associated with
      L&F. Genetic associations between BO-NEQ and LOCO, L&F, and MAMM were moderate to
      high (0.30 to 0.50), but estimates between BONEQ and RLS and FA were not
      significantly different from zero. Locomotion score had a very high genetic
      (0.98) and phenotypic (0.78) correlation with L&F, indicating that both traits
      are genetically the same. On the basis of the genetic parameters, including BONEQ
      in a selection index as a predictor of longevity is promising, but further
      information on its association with longevity is required.

PMID- 18096955
TI  - Negative influence of high maternal milk production before and after conception
      on offspring survival and milk production in dairy cattle.
AB  - There is a paucity of studies on the effect of intrauterine conditions on
      subsequent progeny performance in dairy cows. Using a large national data set on
      Irish Holstein-Friesian dairy cows, the objective of this study was to determine
      if intrauterine conditions, quantified by a maternal genetic variance component,
      significantly affected milk production, age at first calving, calving interval,
      somatic cell score (natural logarithm of somatic cell count) and survival in
      first-, second-, and third-parity female offspring. Maternal genetic variance for
      each trait in each parity was estimated in a linear mixed model which included,
      other than fixed effects, direct additive genetic, maternal genetic, cytoplasmic
      and permanent environmental effect of the dam, and residual component. A
      covariance was also estimated between the direct additive and maternal genetic
      components where possible. Because calves in Irish dairy herds are separated from
      dams at birth, a significant maternal genetic variance (with all other random
      effects in the model) indicates a prepartum maternal effect. A significant
      maternal genetic variance was estimated for 305-d milk yield in first and third
      lactation, somatic cell score in first lactation, and survival to second
      lactation from 188,144 lactations on 80,881 animals. Where estimated, a negative
      correlation existed between the direct additive and maternal genetic components.
      Regression of maternal mixed model solutions on dam milk production at different
      stages relative to conception revealed that greater milk yield preconception and
      during gestation was associated with reduced survival and milk yield and greater
      somatic cell count in the progeny. This study suggests that offspring survival
      and performance are affected by prepartum conditions that offspring experience as
      an oocyte, embryo, or fetus, one of which is mediated through milk production (or
      factors related to milk production) of the dam.

PMID- 18096957
TI  - A theoretical framework for deriving direct economic values for body tissue
      mobilization traits in dairy cattle.
AB  - The aim of this study was to simplify the description of body tissue mobilization
      during first lactation into 3 parameters for which breeding values can be
      estimated. The traits defined were 1) the rate at which a bull's daughters lost
      body energy early in lactation, 2) the maximum drop in body energy content, and
      3) the rate at which a bull's daughters regained body energy after nadir. A
      theoretical framework was developed to derive economic values for the 3 traits of
      body tissue mobilization. The UK population parameters were used in the economic
      framework to derive economic weights for body tissue mobilization during
      lactation. Assuming the average calving pattern in the UK, the economic value for
      the maximum drop in body energy content is small and negative at -0.14 pence
      (p/MJ). The economic value for the rate of loss of body energy in early lactation
      is also negative (-3.1 p/MJ) and for the rate of body energy gain in later
      lactation is positive (19.7 p/MJ). Results showed that the economic values for
      the 3 traits of body tissue mobilization change dramatically depending on the
      date of calving due to changes in feed costs in different seasons. The framework
      was developed to accommodate various system parameters (e.g., the costs of
      differing energy sources throughout the year and calving pattern), thus allowing
      for farm-system-specific economic values for body tissue mobilization. The
      framework provides a method to select sires based on an index of body energy
      mobilization of their daughters.

PMID- 18096958
TI  - Short communication: Carora cattle show high variability in alpha(s1)-casein.
AB  - The objective of this study was to analyze the genetic variability of milk
      proteins of the Carora, a shorthorned Bos taurus cattle breed in Venezuela and in
      other Southern American countries that is primarily used for milk production. A
      total of 184 individual milk samples were collected from Carora cattle in 5 herds
      in Venezuela. The milk protein genes alpha(s1)-casein (CN) (CSN1S1), beta-CN
      (CSN2), kappa-CN (CSN3), and beta-lactoglobulin (LGB) were typed at the protein
      level by isoelectrofocusing. It was necessary to further analyze CSN1S1 at the
      DNA level by a PCR-based method to distinguish CSN1S1*G from B. Increased
      variation was found in particular at the CSN1S1 gene, where 4 variants were
      identified. The predominant variant was CSN1S1*B (frequency = 0.8). The second
      most common CSN1S1 variant was CSN1S1*G (0.101), followed by CSN1S1*C (0.082).
      Moreover, a new isoelectrofocusing pattern was identified, which may result from
      a novel CSN1S1 variant, named CSN1S1*I, migrating at an intermediate position
      between CSN1S1*B and CSN1S1*C. Six cows carried the variant at the heterozygous
      condition. For the other loci, predominance of CSN2*A2 (0.764), CSN3*B (0.609),
      and LGB*B (0.592) was observed. Haplotype frequencies (AF) at the CSN1S1-CSN2
      CSN3 complex were also estimated by taking association into account. Only 7
      haplotypes showed AF values >0.05, accounting for a cumulative frequency of
      0.944. The predominant haplotype was B-A2-B (frequency = 0.418), followed by B-A2
      A (0.213). The occurrence of the G variant is at a rather high frequency, which
      is of interest for selection within the Carora breed because of the negative
      association of this variant with the synthesis of the specific protein. From a
      cheese-making point of view, this variant is associated with improved milk
      clotting parameters but is negatively associated with cheese ripening. Thus, milk
      protein typing should be routinely carried out in the breed, with particular
      emphasis on using a DNA test to detect the CSN1S*G variant. The CSN1S*G allele is
      likely to have descended from the Brown Swiss, which contributed to the Carora
      breed and also carries this allele.

PMID- 18096956
TI  - Short communication: Allele, genotype, and haplotype data for bovine spongiform
      encephalopathy-resistance polymorphisms from healthy US Holstein cattle.
AB  - Bovine spongiform encephalopathy (BSE) is a neurodegenerative disease of cattle
      caused by abnormally folded prion proteins. Two regulatory region polymorphisms
      in the bovine prion gene are associated with resistance to classical BSE disease:
      a 23-bp region in the promoter that contains a binding site for the repressor
      protein RP58, and a 12-bp region in intron 1 that has a binding site for the
      transcription factor SP1. The presence of these binding sites enhances BSE
      resistance in cattle, whereas cattle that lack these regions are more susceptible
      to the disease. The present study examined the allele, genotype, and haplotype
      frequencies for the 23-bp and 12-bp polymorphisms in Holstein cattle from 9
      different US states, and these frequencies were compared with data previously
      established for Holstein cattle from the United Kingdom, Germany, and Japan.
      Additionally, the coding region of the prion gene was sequenced from the US
      samples. Finally, archival samples from US Holstein sires born between 1953 and
      1957 were analyzed. We found that the resistant allele and genotype frequencies
      for the US Holstein cattle were as high, or higher, relative to that observed in
      other countries. Furthermore, the current US frequencies were comparable to those
      determined in the archival samples from the 1950s. Based on the frequencies of
      these regulatory region polymorphisms, the US Holstein population is not at a
      greater risk for BSE than Holsteins worldwide.

PMID- 18096959
TI  - Technical note: Computing strategies in genome-wide selection.
AB  - Genome-wide genetic evaluation might involve the computation of BLUP-like
      estimations, potentially including thousands of covariates (i.e., single
      nucleotide polymorphism markers) for each record. This implies dense Henderson's
      mixed-model equations and considerable computing resources in time and storage,
      even for a few thousand records. Possible computing options include the type of
      storage and the solving algorithm. This work evaluated several computing options,
      including half-stored Cholesky decomposition, Gauss-Seidel, and 3 matrix-free
      strategies: Gauss-Seidel, Gauss-Seidel with residuals update, and preconditioned
      conjugate gradients. Matrix-free Gauss-Seidel with residuals update adjusts the
      residuals after computing the solution for each effect. This avoids adjusting the
      left-hand side of the equations by all other effects at every step of the
      algorithm and saves considerable computing time. Any Gauss-Seidel algorithm can
      easily be extended for variance component estimation by Markov chain-Monte Carlo.
      Let m and n be the number of records and markers, respectively. Computing time
      for Cholesky decomposition is proportional to n3. Computing times per round are
      proportional to mn2 in matrix-free Gauss-Seidel, to n2 for half-stored Gauss
      Seidel, and to n and m for the rest of the algorithms. Algorithms were tested on
      a real mouse data set, which included 1,928 records and 10,946 single-nucleotide
      polymorphism markers. Computing times were in the order of a few minutes for
      Gauss-Seidel with residuals update and preconditioned conjugate gradients, more
      than 1 h for half-stored Gauss-Seidel, 2 h for Cholesky decomposition, and 4 d
      for matrix-free Gauss-Seidel. Preconditioned conjugate gradients was the fastest.
      Gauss-Seidel with residuals update would be the method of choice for variance
      component estimation as well as solving.

PMID- 18096960
TI  - Short communication: Genetic analysis of respiratory disease in Norwegian Red
      calves.
AB  - A genetic analysis of respiratory disease (RD) in Norwegian Red calves was
      conducted. This is the first genetic study of calf diseases based on data from
      the Norwegian health recording system, and RD was chosen because it is the most
      frequent disease in calves. Records on absence or presence of RD before 180 d of
      age for 250,212 calves (progeny of 728 Norwegian Red artificial insemination
      sires) were analyzed with a threshold model. A total of 0.7% of the calves had
      veterinary treatment of RD before 180 d of age. Heritability of RD in the
      underlying scale was 0.05, with a 95% credibility interval from 0.02 to 0.09. The
      "worst" sire had a predicted probability of RD that was more than twice as high
      as that of the "best" one (1.15 vs. 0.44%). Their 95% credibility intervals for
      predicted probability of RD, however, overlapped. With improved and more
      extensive recording of calf diseases, the precision in genetic evaluation of
      sires could increase considerably. The frequency of RD is very low in the
      Norwegian Red population at present, so there is not much scope for genetic
      improvement. However, this study indicates that reasonably precise genetic
      evaluation of sires for resistance to RD could be feasible.

PMID- 18096961
TI  - Genetic parameters of milk coagulation properties and their relationships with
      milk yield and quality traits in Italian Holstein cows.
AB  - Milk coagulation properties (MCP) are an important aspect in assessing cheese
      making ability. Several studies showed that favorable conditions of milk
      reactivity with rennet, curd formation rate, and curd strength, as well as curd
      syneresis, have a positive effect on the entire cheese-making process and
      subsequently on the ripening of cheese. Moreover, MCP were found to be heritable,
      but little scientific literature is available about their genetic aspects. The
      aims of this study were to estimate heritability of MCP and genetic correlations
      among MCP and milk production and quality traits. A total of 1,071 Italian
      Holstein cows (progeny of 54 sires) reared in 34 herds in Northern Italy were
      sampled from January to July 2004. Individual milk samples were collected during
      the morning milking and analyzed for coagulation time (RCT), curd firmness (a30),
      pH, titratable acidity, fat, protein, and casein contents, and somatic cell
      count. About 10% of individual milk samples did not coagulate in 31 min, so they
      were removed from the analyses. Estimates of heritability for RCT and a30 were
      0.25 +/- 0.04 and 0.15 +/- 0.03, respectively. Estimates of genetic correlations
      between MCP traits and milk production traits were negligible except for a30 with
      protein and casein contents (0.44 +/- 0.10 and 0.53 +/- 0.09, respectively).
      Estimates of genetic correlations between MCP traits and somatic cell score were
      strong and favorable, as well as those between MCP and pH and titratable acidity.
      Selecting for high casein content, milk acidity, and low somatic cell count might
      be an indirect way to improve MCP without reducing milk yield and quality traits.

PMID- 18096962
TI  - Effects of clustering herds with small-sized contemporary groups in dairy cattle
      genetic evaluations.
AB  - Most test-day models used in genetic evaluations of dairy cattle define
      contemporary groups (CG) as the herd-test-date effect. Fitting this effect as
      fixed may minimize prediction bias, but requires a minimum number of observations
      per CG to simultaneously maximize the effective number of observations and
      minimize the residual error and prediction error variance. Nearly 4 million test
      day records from the Portuguese Holstein database of 238,271 cows calving in
      1,330 herds from 1994 through 2006 were used to evaluate the effect of clustering
      CG from small herds based on the similarity of their production environments.
      Principal component analysis was used to summarize 14 descriptive variables in 5
      eigenvectors that explained 88% of the total variation. Based on the distance
      matrix, 2 different approaches were applied to group the herds. For each
      approach, 4 data sets were built having at least 3, 5, 10, or 15 observations per
      CG, respectively. For the data sets of group A, all herds, with or without the
      required number of observations per CG, were used in the clustering process. For
      the data sets of group B, only herds without the minimum number of observations
      were candidates to form clusters. All data sets were analyzed by an
      autoregressive test-day animal model fitting a fixed herd test date in a multiple
      lactation setting, and results were compared with the current clustering
      procedure used in the Portuguese genetic evaluations. The data set from group B,
      with a minimum of 3 records per CG, was the one that provided the highest
      accuracy of prediction and the smaller within-CG variance, revealing a better fit
      for the data. This procedure also preserved the original herd structure of the
      database, better maximizing the number of herd groups. Correlations among EBV,
      rank, prediction error variance, and accuracies of prediction for this data set
      were high (0.97, 0.97, 0.85, and 0.82, respectively), suggesting that no major
      reranking is to be expected.

PMID- 18096963
TI  - Genetic parameters for major milk fatty acids and milk production traits of Dutch
      Holstein-Friesians.
AB  - The objective of this study was to estimate genetic parameters for major milk
      fatty acids and milk production traits. One morning milk sample was collected
      from 1,918 Holstein-Friesian heifers located in 398 commercial herds in The
      Netherlands. Each sample was analyzed for total percentages of fat and protein,
      and for detailed fatty acid percentages (computed as fatty acid weight as a
      proportion of total fat weight). Intraherd heritabilities were high for C4:0 to
      C16:0, ranging from 0.42 for C4:0 to 0.71 for C10:0. Saturated and unsaturated
      C18 fatty acids had intraherd heritability estimates of approximately 0.25,
      except for C18:2 cis-9, trans-11, which was 0.42. Standard errors of the
      heritabilities were between 0.07 and 0.12. Genetic correlations were high and
      positive among C4:0 to C14:0, as well as among unsaturated C18, but correlations
      of C4:0 to C14:0 with unsaturated C18 were generally weak. The genetic
      correlation of C16:0 with fat percentage was positive (0.65), implying that
      selection for fat percentage should result in a correlated increase of C16:0,
      whereas unsaturated C18 fatty acids decreased with increasing fat percentage (
      0.74). Milk fat composition can be changed by means of selective breeding, which
      offers opportunities to meet consumer demands regarding health and technological
      aspects.

PMID- 18096964
TI  - Exploration of relationships between claw disorders and milk yield in Holstein
      cows via recursive linear and threshold models.
AB  - Relationships between claw disorders and test-day milk yield recorded in 2005 on
      5,360 Holstein cows, kept on 11 large-scale dairy farms in eastern Germany, were
      analyzed in a Bayesian framework with standard linear and threshold models and
      recursive linear and threshold models. Four different claw disorders, digital
      dermatitis (DD), sole ulcer (SU), wall disorder (WD), and interdigital
      hyperplasia (IH), were scored as binary traits within 200 d after calving and
      analyzed separately. Incidences of disorders were 13.7% for DD, 16.5% for SU,
      9.8% for WD, and 6.7% for IH. Heritabilities of disorders were greater when
      applying threshold or recursive threshold models than with linear or linear
      recursive models. Posterior means of genetic correlations between test-day milk
      production and claw disorders ranged from 0.17 to 0.44, suggesting that breeding
      strategies focusing on increased milk yield will increase incidences of disorders
      as a correlated response. A progressive path of lagged relationships was
      postulated for recursive models describing first the influence of test-day milk
      yield (MY1) on claw disorders and second, the effect of the disorder on milk
      production level at the following test day (MY2). In recursive models, structural
      coefficients describe recursive relationships at the phenotypic level. The
      structural coefficient lambda21 was the gradient of disease (trait 2) with
      respect to MY1 (trait 1) for a model with a recursive effect of trait 1 on trait
      2. The increase of disease incidence of the 4 different disorders per 1-kg
      increase of MY1 ranged from lambda21 = 0.006 to lambda21 = 0.024 on the visible
      scale when applying recursive linear models, and from lambda21 = 0.003 to
      lambda21 = 0.016 on the underlying liability scale for recursive threshold
      models. The rate of change in MY2 (trait 3) with respect to the previous claw
      disorder is given by lambda32 for a model with a recursive effect from trait 2 to
      trait 3. Structural coefficients lambda32 ranged from -0.12 to -0.68 predicting
      that a 1-unit increase in the incidence of any disorder reduces milk yield at the
      following test day by up to 0.67 kg. Rank correlations between sire posterior
      means for the same claw disorders among different models were >0.84, but some
      changes in rank of sires in distinct top-10 lists were observed. Structural
      equation models are of increasing importance in genetic evaluations, and this
      study showed the possible application of recursive systems, even for categorical
      data.

PMID- 18096965
TI  - Polymorphisms in the 5' upstream region of the CXCR1 chemokine receptor gene, and
      their association with somatic cell score in Holstein cattle in Canada.
AB  - Identification of regulatory elements in 5' regions of chemokine genes is
      fundamental for understanding chemokine gene expression in response to infection
      diseases. The CXCR1 receptor is expressed on the surface of neutrophils and
      interacts primarily with CXCL8 (IL-8), the most potent chemoattractant for
      neutrophils. The aim of this study was to characterize the 5' upstream region
      (2.1 kb) of the bovine CXCR1 chemokine receptor gene for polymorphism content and
      to identify in silico potential transcription-factor binding sites. The 5'
      flanking region was found by mining the NCBI GenBank (www.ncbi.nlm.nih.gov/). A
      DNA sequence from the whole genome shotgun sequence project with reference number
      AC150887.4 contained the CXCR1 5' flanking sequence. Computer analysis revealed
      potential binding sites for the transcription factors nuclear factor kappaB (NF
      kappaB), binding factor GATA-1, barbiturate inducible element (Barbie), nuclear
      factor of activated T-cells, and activator protein 1. Polymorphism discovery in
      this region was conducted by constructing an inclusive DNA pool including 2
      phenotypic extreme groups, 20 bulls with high estimated breeding values (EBV) for
      somatic cell score (SCS), and 20 bulls with low EBV for SCS. Independent
      amplicons along the 5' flanking region of bovine CXCR1 were generated for
      polymorphism discovery by sequencing. Three novel single nucleotide polymorphisms
      (SNP), CXCR1c.-344T>C, CXCR1c.-1768T>A, and CXCR1c.-1830A>G, and a previously
      identified SNP in the coding region, CXCR1c.777G>C, were identified. The 4 SNP
      were genotyped in Canadian Holstein bulls (n = 338) using tetra-primer
      amplification refractory mutation system (ARMS)-PCR. Average allele substitution
      effects were estimated to investigate associations between the 4 SNP and EBV for
      SCS in first, second, and third and later lactations. Multiple trait analysis
      revealed that the SNP CXCR1c.-1768T>A was associated with EBV for SCS in the
      first and second lactations and over all 3 lactations. Haplotype analysis
      substantiated this association with EBV for SCS in the first lactation. Given the
      location of SNP CXCR1c.-1768T>A and the surrounding potential binding recognition
      sequences for NF-kappaB, GATA-1, and Barbie transcription-factors, this SNP may
      be implicated in gene regulation and warrants further research.

PMID- 18096966
TI  - Economic evaluation of the breeding goal for Norwegian Red dairy cattle.
AB  - In this paper, a translog profit function was applied to estimate the economic
      values of the traits included in the breeding goal for Norwegian Red dairy
      cattle. The following 10 traits are included in the breeding goal: milk, meat,
      mastitis resistance, fertility, calving difficulties, stillbirths, other
      diseases, udder, temperament, and legs. An empirical implementation that locally
      approximates the unknown true profit function was suggested and estimated, taking
      farm heterogeneity into account. The model was applied to a panel data set of
      3,259 Norwegian dairy farms over the period 1999 to 2003. Panel data, also called
      longitudinal or cross-sectional time-series data, are multiple cases (cows,
      farms, countries, etc.) observed over 2 or more time periods. The data set
      consisted of farm-level data, including production and economic data from the
      farm and the estimated breeding values for each cow's sire. The estimated
      economic values make it possible to test whether genetic selection has been
      profitable for the farmer, and the extent to which the currently used economic
      values were optimal during the period 1999 to 2003. Although the translog profit
      function is quite flexible, it is rather complex, and a simplified version of the
      model, a Cobb-Douglas profit function, was also estimated. However, the
      hypothesis that this simpler function adequately describes the data compared with
      the full translog model was rejected. Further, the hypothesis that the estimated
      breeding values are profit neutral was rejected (i.e., the hypothesis that there
      are no interactions between input and output prices on one hand and estimated
      breeding values on the other). These results indicated that selection not only
      leads to a parallel shift in profits, but also to changes in input use. Seven of
      the 10 traits had a significant effect on the farmers' profit. The 3 traits that
      were not significant were calving difficulty, stillbirth, and other diseases. The
      results showed that the breeding program for Norwegian Red cattle has been fairly
      successful in improving farmers' profits. However, a slight modification of the
      breeding goal, such as a reduction in the weights for stillbirths and other
      diseases and an increase in the weights for meat and temperament, would increase
      farm profits.

PMID- 18096967
TI  - Predicting somatic cell count standard violations based on herd's bulk tank
      somatic cell count. Part I: Analyzing variation.
AB  - The present study examines the relationship between the bulk tank somatic cell
      count (SCC) mean and sigma (an estimate of variation) and the probability of
      exceeding a SCC standard. Daily or every other day, bulk tank SCC data were
      collected for 24 mo from 1,501 herds. Mean and sigma were estimated for each herd
      monthly and were compared between months and herd production categories using
      Kruskal-Wallis nonparametric ANOVA. The effect of month on bulk tank SCC mean and
      sigma was significant, with estimates for all summer months and most of the
      spring and fall months being significantly greater than estimates of mean and
      sigma in December 2004. Logistic regression models were developed to examine the
      relationship between month and herd production and the odds of a herd exceeding a
      SCC standard. The odds of exceeding a bulk tank SCC standard were significantly
      greater in the summer months and for smaller herds. A grid was constructed
      determining the probability of exceeding any of 5 SCC standards (200,000 to
      600,000 cells/mL, step 100,000 cells/mL) in the following month, based on the
      mean and sigma of the past month. The violation probability grid can be used to
      assess the prospect of meeting quality premium goals and to proactively encourage
      more consistent performance in all the processes affecting bulk tank SCC.

PMID- 18096968
TI  - Predicting somatic cell count standard violations based on herd's bulk tank
      somatic cell count. Part II: Consistency index.
AB  - The present study examines the capability of 1,501 herds in the Upper Midwest and
      the performance of statistical process control charts and indices as a way of
      monitoring and controlling milk quality on the farm. For 24 mo, daily or every
      other day bulk tank somatic cell count (SCC) data were collected. Consistency
      indices for 5 different SCC standards were developed. The indices calculate the
      maximum variation allowed to meet a desired SCC level at a given mean bulk tank
      SCC and were used to identify herds not capable of meeting a specific SCC
      standard. Consistency index method was compared with a test identifying future
      bulk tank SCC standard violators based on herds' past violations. The performance
      of the consistency index test and the past violation method was evaluated by
      logistic regression. The comparison focused on detection probability and
      certainty associated with a result. For the 5 SCC levels, detection probability
      and certainty associated with a result ranged from 51 to 98%. Detection
      probability of all violators and certainty associated with a negative result was
      greater for the consistency index across all 5 SCC levels (by 0.7 to 7.4% and 2.1
      to 5.1%, respectively). Control charts were plotted and monthly consistency
      indices calculated for individual farms. Charts in combination with the
      consistency indices would warn from 66 to 80% of the herds about an upcoming
      violation within 30 d before it occurred. They offer a proactive approach to
      maintaining consistently high milk quality. By assessing process capability and
      distinguishing between significant changes and random variation in bulk tank SCC,
      tools presented in this article encourage fact-based decisions in dairy farm milk
      quality management.

PMID- 18096969
TI  - Psychometric properties of the Beck Depression Inventory II (BDI-II) among
      community-dwelling older adults.
AB  - The psychometric properties of the Beck Depression Inventory-II (BDI-II) as a
      self-administered screening tool for depressive symptoms were examined in a
      sample of community-dwelling older and younger adults. Participants completed the
      BDI-II, the Center for Epidemiologic Studies Depression Scale, the Coolidge Axis
      II Inventory, the Perceived Stress Scale, and the Short Psychological Well-Being
      Scale. Internal reliability of the BDI-II was found to be good among older and
      younger adults. The average BDI-II depression score did not differ between
      younger and older adults. Solid evidence for convergent and discriminant validity
      was demonstrated by correlations between the BDI-II with the other measures. The
      BDI-II appears to have strong psychometric support as a screening measure for
      depression among older adults in the general population. Implications for using
      the BDI-II as an assessment instrument in behaviorally based psychotherapy are
      discussed.

PMID- 18096970
TI  - Positive antecedent and consequent components in child compliance training.
AB  - This study evaluates the effects of positive antecedent (effective instruction
      delivery and time-in) and consequent components (contingent praise) on the
      compliance of 4 children in a clinic setting. Results suggest that the use of
      effective instruction delivery alone increased compliance above baseline levels
      for the 4 children and that the additions of time-in and contingent praise
      further increased compliance for 3 of the 4 children. All three positive
      treatment components resulted in compliance greater than 80% for all children.
      Compliance levels were maintained at 1-month follow-up for 2 children. Results
      are discussed in terms of the benefits to using all of the positive components in
      compliance training.

PMID- 18096971
TI  - Errorless acquiescence training: a potential "keystone" approach to building peer
      interaction skills in children with severe problem behavior.
AB  - Errorless acquiescence training (EAT) was developed as a graduated, success
      focused, and short-term intervention for building social skills. The approach
      focuses on building the skill of acquiescence (i.e., teaching children to be
      flexible with the needs and will of peers). The authors predict that acquiescence
      would serve as a keystone, that is, a skill that when trained produces widespread
      improvements in child behavior, including reductions in antisocial behavior. The
      authors provide EAT to eight children referred to a clinical classroom for severe
      antisocial behavior. Consistent with errorless paradigms, key intervention
      components present at the initiation of intervention are systematically faded at
      a slow enough rate to ensure continued prosocial interactions throughout and
      following treatment. Children demonstrate substantial increases in acquiescent
      responding and other prosocial behavior as well as covariant reductions in
      antisocial behaviors. Acquiescence is discussed in terms of its potential as a
      keystone for prosocial responding in children with antisocial behavior.

PMID- 18096972
TI  - A review of behavioral treatments for self-injurious behaviors of persons with
      autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) are considered to be among the most serious of
      the mental health conditions. Concomitant with many cases of ASD is intellectual
      disability. Further compounding the disability is the fact that both conditions
      are known risk factors for self-injurious behavior (SIB). To date, the most
      effective intervention methods, based on the available data, appear to be
      variants of behavior modification. This article provides an overview of the
      current status of learning-based interventions for SIB in ASD and provides a
      review of specific studies. Although most studies describe some combination of
      reinforcement and punishment procedures, efforts are under way to develop more
      positively oriented strategies, such as functional assessment, to decrease the
      use of punishment. However, almost all the treatment studies employ single case
      designs, thus preventing a comparison of treatment efficacy. These issues are
      discussed along with other strengths, weaknesses, and future directions for
      clinical practice and treatment.

PMID- 18096973
TI  - Cognitive-behavioral interventions to reduce suicide behavior: a systematic
      review and meta-analysis.
AB  - Suicide behavior is a serious clinical problem worldwide, and understanding ways
      of reducing it is a priority. A systematic review and meta-analysis were carried
      out to investigate whether Cognitive-behavioral therapies (CBTs) would reduce
      suicide behavior. From 123 potential articles, 28 studies met the entry criteria.
      Overall, there was a highly significant effect for CBT in reducing suicide
      behavior. Subgroup analysis indicates a significant treatment effect for adult
      samples (but not adolescent), for individual treatments (but not group), and for
      CBT when compared to minimal treatment or treatment as usual (but not when
      compared to another active treatment). There was evidence for treatment effects,
      albeit reduced, over the medium term. Although these results appear optimistic in
      advocating the use of CBT in ameliorating suicidal thoughts, plans, and
      behaviors, evidence of a publication bias tempers such optimism.

PMID- 18096974
TI  - Cutoff scores for the Matson Evaluation of Social Skills for Individuals With
      Severe Retardation (MESSIER) for adults with intellectual disability.
AB  - Social skills are defining aspects of intellectual disability (ID). Additionally,
      their presence or absence can be a major impediment to independent living, and
      they correlate with other problems in the ID population, such as comorbid
      psychopathology. To date, little has been done to develop scales to measure these
      problems, particularly for adults. One exception has been the Matson Evaluation
      of Social Skills for the Severely Retarded (MESSIER). The scale has well
      established reliability, however many of its psychometric properties have yet to
      be explored. This study was designed to establish cutoff scores for the total
      score and factors and to explore the relationship of individual items to severity
      of social deficits. Participants are adults with severe or profound ID, assessed
      on the MESSIER. Specific psychometrics for the test including cutoff scores are
      established. The implications of these data for theory, research, and practice
      are discussed.

PMID- 18096975
TI  - A group contingency program to improve the behavior of elementary school students
      in a cafeteria.
AB  - Studies of behavior modification interventions for disruptive behavior in schools
      have generally focused on classroom behavior with less research directed toward
      child behavior in other school settings (e.g., cafeterias). The present report
      documents the effect of a group contingency intervention with a random reward
      component, targeting disruptive cafeteria behavior. An uncontrolled study of the
      effect of the group contingency program across the school year suggested
      substantial behavior improvement after the program started. Two natural treatment
      discontinuations during the same school year provide further support for the
      intervention. Both sources of information suggest behavioral improvement in rule
      following behavior when the program was actively implemented.

PMID- 18096976
TI  - The Law Enforcement Officer Stress Survey (LEOSS): evaluation of psychometric
      properties.
AB  - This study establishes the reliability and validity of the Law Enforcement
      Officer Stress Survey (LEOSS), a short early-warning stress-screening measure for
      law enforcement officers. The initial phase of LEOSS development employed the
      behavioral-analytic model to construct a 25-item instrument specifically geared
      toward evaluation of stress in this population. The purpose of the present study
      was to examine psychometric properties of the LEOSS. Results indicate this
      instrument has good levels of internal consistency, test-retest reliability, and
      validity. Potential applications of the LEOSS in clinical and research contexts
      are discussed. The next phase of research on the LEOSS is discussed, and
      suggestions for directions that future research in this area might take are
      offered.

PMID- 18096977
TI  - Proliferation of degrees in nursing: a call for clarity.

PMID- 18096978
TI  - Expanding nursing perspectives on loss and grieving.
AB  - This column seeks to contribute to the understanding of the concept of grieving a
      loss through capturing the indivisible, unpredictable, ever-changing nature of
      this universal human experience. Through the process of concept inventing the
      extant theoretical knowledge concerning grief and loss, classical literature, and
      the humanbecoming theory and research literature were considered, revealing the
      idea that grieving a loss is persistent but the meaning of the experience
      continually changes. Knowledge of the persistent, ever-changing nature of
      grieving a loss is important for nurses who use humanbecoming theory as a guide
      while abiding with those who grieve a loss.

PMID- 18096979
TI  - Political boundaries in research.
AB  - In many ways, the current political climate is antithetical to sound research. As
      an example, Roye shares her experiences attempting to obtain funding to study
      ways to promote risk-reduction behaviors among sexually active teens when the
      political agenda focuses on abstinence only. She details a program of funded
      research that she embarked on prior to the current administration. She describes
      how she found her work blocked, as she attempted to continue with research
      designed to identify factors associated with heterosexual anal intercourse among
      female teens. Her purpose was to design prevention strategies for reducing the
      incidence of HIV/AIDS among young women of color. She further describes her
      feelings when finding herself on the hit list of scientists whose work was deemed
      objectionable for ideological reasons and she shares current activities that
      various organizations are engaged in to protest the political obstruction of
      scientific investigation.

PMID- 18096980
TI  - Boundaries: ethical implications for what it means to be therapeutic in the nurse
      person relationship.
AB  - The nurse-person relationship is sometimes regarded as the essence of
      professional nursing practice. Many biomedical nursing definitions and
      connotations have emerged over time for what it means to practice professional
      nursing with boundaries in a therapeutic nurse-person relationship. In this
      column the author compares, contrasts, and offers a unique disciplinary
      perspective with regard to these terms. Ethical implications for developing
      professional relationships through the nursing disciplinary lens of the human
      becoming school of thought are explored.

PMID- 18096981
TI  - The gifts of silence and solitude.
AB  - In this column the author describes the importance of finding silence and
      solitude amid the noise and technology present today in the teaching-learning
      academy. Three gifts of silence and solitude are identified: the gift of
      comforting aloneness, the gift of vision for new horizons, and the gift of a
      sense of freedom. A humanbecoming perspective is used to explore the implications
      of these gifts. This column introduces a column by Diana Vander Woude describing
      her teaching-learning experience in leadership focusing on silence and solitude.

PMID- 18096982
TI  - Theory derivation and the telenovela: facilitating Mexican-American family use of
      home healthcare.

PMID- 18096983
TI  - Practicing women's health with a simultaneity worldview in a medical model world.
AB  - Practicing from a humanbecoming perspective is challenging and rewarding for the
      nurse clinician. In this column, the author discusses the challenges faced when
      working as a women's health nurse practitioner, with a simultaneity worldview, in
      a medical model world.

PMID- 18096984
TI  - The practice of nursing science: crossing boundaries.
AB  - This column presents descriptions of how four nurse researchers practice science,
      based upon a framework constructed to depict key dimensions in the practice of
      nursing science. Emphasis is given to the role of theory in science.

PMID- 18096985
TI  - Truth for the moment: personal testimony as evidence.
AB  - The purpose of this article is to set forth an alternative to the traditional
      view of evidence, that which counts aggregate data synthesized from the results
      of quantitative research as desirable healthcare outcomes. Truth for the moment
      as evidence from qualitative research raises the discourse to another level and
      is described in light of the humanbecoming school of thought.

PMID- 18096986
TI  - The relation of meditation to power and well-being.
AB  - The purpose of this research is to examine the relation of meditation to power
      and well-being in Korean adults. Using a quasi-experimental design, meditation
      was provided through a chakra meditation music program over a 4 week period. The
      Power as Knowing Participation in Change Tool and the Well-Being Picture Scale
      were used, after being translated into Korean. Statistically significant
      interaction effects of power and group (p<.001), and well-being and group (p<.05)
      were found. Meditation has a potential to facilitate power and well-being in the
      human and environmental field patterning process.

PMID- 18096987
TI  - Feeling listened to: a lived experience of humanbecoming.
AB  - The purpose of this study is to discover the structure of the universal lived
      experience of feeling listened to, a phenomenon of health and quality of life
      related to the human-to-human relationship. This Parse research method study
      included 10 adults who shared their experiences of feeling listened to. The
      structure, feeling listened to is unreserved affirmation amid potential
      irreverence arising with the liberating contentment of benevolent affiliations,
      is the central finding of the study. This finding was connected to humanbecoming
      theory and extant literature, contributing to nursing knowledge, expanding the
      theory, and enhancing understanding about feeling listened to.

PMID- 18096988
TI  - Yes, Virginia, nursing does have laws.
AB  - In this article the author explores the possibility of the emergence of nursing
      laws as a natural consequence of the maturation and evolution of selected areas
      of nursing knowledge. To support this proposition, the evolution of social and
      scientific laws and their meanings are discussed. In addition, the roles that
      empirical validation and logical adequacy play in epistemological development,
      including the development of discipline-specific laws, are explored. Two areas of
      nursing knowledge in which laws may be emerging, as well as the foundation of
      these laws, are identified.

PMID- 18096989
TI  - Is hope fragile?
AB  - The communication of bad news to patients in a sensitive and supportive manner is
      a challenging part of healthcare practice, in part because of the cultural
      differences and ethical dilemmas that complicate such discussions. One of the
      barriers to nurse-patient communication has been the assumption that hope is
      fragile. Sometimes this assumption is held by nurses, and sometimes it is held by
      patients or their families. Reasons for confidence in hope are discussed.

PMID- 18096990
TI  - Telling the truth: Turkish patients' and nurses' views.
AB  - The objective of this study was to investigate nurses' communications with
      patients, particularly regarding getting accurate and truthful information about
      their medical diagnosis and prognosis. This survey research involved 166 nurses
      and 435 patients at the Osmangazi University Hospital, Turkey. Although 90% of
      the nurses said that patients should be informed about their diagnosis, only 66%
      of the patients said they wanted to be told this information. For those who
      wanted to be informed, how they should be informed is also discussed.

PMID- 18096992
TI  - Glucocorticoid repression of human with-no-lysine (K) kinase-4 gene expression is
      mediated by the negative response elements in the promoter.
AB  - With-no-lysine (K) kinase-4 (WNK4) is a serine/threonine kinase that plays an
      essential role in the regulation of fluid and electrolyte homeostasis. The
      effects of glucocorticoids, key physiological regulators, on the WNK4 gene
      expression are still unknown. Here, we used dexamethasone (Dex) to treat the
      human embryo kidney 293 (HEK293) cells and found a decrease of human WNK4 (hWNK4)
      mRNA level by northern blot and real-time quantitative PCR. After an hWNK4
      transcriptional initiation site was located by 5' rapid amplification of cDNA end
      assay, a series of 5'-deleted hWNK4 promoter-luciferase constructs were generated
      by PCR. Transfection of these constructs in COS-7 and HEK293 cells revealed that
      Dex inhibited the hWNK4 transcriptional activity in glucocorticoid receptor (GR)
      dependent pattern. Two negative glucocorticoid response elements (nGREs) were
      identified at -285 and -337 of the hWNK4 gene promoter and the GR binding
      activity to them was increased by Dex as shown by electrophoretic mobility shift
      assay and chromatin immunoprecipitation. In summary, these data demonstrated that
      hWNK4 was a new glucocorticoid-regulated gene whose expression was inhibited
      through the interaction of GR with nGREs in the promoter region.

PMID- 18096993
TI  - Destabilization of parathyroid hormone mRNA by extracellular Ca2+ and the
      calcimimetic R-568 in parathyroid cells: role of cytosolic Ca and requirement for
      gene transcription.
AB  - Extracellular Ca reduces parathyroid hormone (PTH) levels through several
      mechanisms, but many details of the intracellular steps involved have been
      difficult to elucidate because of the lack of a suitable parathyroid cell model.
      The present studies utilized our Ca-responsive bovine parathyroid organoid
      culture system (pseudoglands) to examine PTH mRNA in intact parathyroid cells.
      Increasing medium calcium from 0.4 to 3.0 mM reduced PTH mRNA to 20-30% of basal
      by 16 h. Reducing medium Ca from 3.0 to 0.4 mM restored PTH mRNA levels over a 24
      h period. PTH mRNA was also reduced by the calcimimetic R-568, confirming the
      role of the calcium-sensing receptor. PTH decay rates were determined by placing
      pseudoglands in either 0.4 or 3.0 mM Ca for 2 h and then blocking gene
      transcription. PTH mRNA remained stable for at least 24 h in pseudoglands
      incubated in 0.4 mM Ca, but fell gradually by 62% in the presence of 3.0 mM Ca.
      Blocking transcription prior to the addition of high-Ca medium dramatically
      blunted the Ca-induced degradation of PTH mRNA, indicating that acceleration of
      PTH mRNA decay by Ca requires gene transcription. Pharmacologic investigation of
      the signaling pathways involved indicated that the Ca-induced reduction of PTH
      mRNA did not involve MAP kinase, phospholipase D, or cyclic AMP. However,
      increasing cytosolic Ca with thapsigargin or the Ca ionophore A23187 decreased
      PTH mRNA levels. In summary, Ca-mediated destabilization of PTH mRNA requires
      gene transcription and involves increases in cytosolic Ca.

PMID- 18096994
TI  - Temporal variation in estrogen receptor-alpha protein turnover in the presence of
      estrogen.
AB  - Estrogen receptor-alpha (ERalpha) is essential in the maintenance of cellular
      responsiveness to estrogen in the reproductive system. It is established that
      ligand binding induces downregulation of ERalpha protein by targeting receptor
      for destruction by the 26S proteasome. However, ERalpha is preserved in cells
      chronically exposed to estrogen and it is unknown how receptor levels are
      maintained in the continued presence of the signal that induces degradation. A
      modified pulse-chase analysis was developed using a tet-inducible ERalpha
      expression system to determine the rate of ERalpha protein decay following both
      acute and chronic estrogen treatments. Upon initial hormone treatment, ERalpha
      half-life is shortened from 3 to 1 h. However, ERalpha half-life increases over
      time, achieving a half-life of approximately 6 h in 72 h of estrogen treatment.
      Analysis of ERalpha half-life in the presence and absence of proteasome
      inhibitor, MG132, revealed that the increased stability is due in part to a
      decreased rate of proteolysis. In addition, we observed a time-dependent increase
      in phospho-S118 ERalpha and showed that the half-life of the phosphomimetic
      ERalpha mutant, S118E-ER, is identical to that of wild-type receptor under
      conditions of chronic estrogen treatment. These data provide evidence that as
      cells adapt to chronic stimulation, ERalpha protein is stabilized due first to a
      decreased rate of proteolysis, and secondarily, to the accumulation of proteasome
      resistant, phosphorylated form of receptor. This temporal control of proteolysis
      allows for the establishment of steady-state levels of receptor and provides a
      protective mechanism against loss of hormone responsiveness.

PMID- 18096995
TI  - G.O.D.'s Holy Grail: discovery of the RAG proteins.

PMID- 18096996
TI  - Pillars article: the V(D)J recombination activating gene, RAG-1. 1989.

PMID- 18096997
TI  - Immune modulation by the human cytomegalovirus-encoded molecule UL18, a mystery
      yet to be solved.
AB  - Human cytomegalovirus infects human populations at a high frequency worldwide.
      During the long coevolution of virus and host, a fine balance has developed
      between viral immune evasion strategies and defense mechanisms of the immune
      system. Human cytomegalovirus encodes multiple proteins involved in the evasion
      of immune recognition, among them UL18, a MHC class I homologue. Despite almost
      20 years of research and the discovery of a broadly expressed inhibitory receptor
      for this protein, its function in immune modulation is not clear yet. Recent data
      suggest that besides inhibitory effects on various immune cells, UL18 may also
      act as an activating component during CMV infection. In this review, we provide
      an overview of the biology of UL18 and discuss several attempts to shed light on
      its function.

PMID- 18096998
TI  - Cutting edge: engagement of NKG2A on CD8+ effector T cells limits immunopathology
      in influenza pneumonia.
AB  - Influenza pneumonia results in considerable lung injury, a significant component
      of which is mediated by CD8+ T cell Ag recognition in the distal airways and
      alveoli. TNF-alpha produced by Ag-specific CD8+ T cells appears primarily
      responsible for this immunopathology, and we have examined the negative
      regulation of CD8+ TNF production by CD94/NKG2A engagement with its receptor, Qa
      1b. TNF production by antiviral CD8+ T cells was significantly enhanced by NKG2A
      blockade in vitro, and mice deficient in the NKG2A ligand, Qa-1b, manifested
      significantly greater pulmonary pathology upon CD8+ T cell-mediated clearance in
      influenza pneumonia. Furthermore, blockade of NKG2A ligation resulted in the
      enhancement of lung injury induced by CD8+ effector cell recognition of alveolar
      Ag in vivo in the absence of infectious virus. These data demonstrate that
      CD94/NKG2A transduces a biologically important signal in vivo to activated CD8+ T
      cells that limits immunopathology in severe influenza infection.

PMID- 18096999
TI  - Cutting edge: a key pathogenic role of IL-27 in T cell- mediated hepatitis.
AB  - The signals driving T cell activation in T cell-mediated fulminant hepatitis are
      not fully understood. In this study, we identify the cytokine IL-27p28/EBI3 as a
      major pathogenic factor in the ConA model of T cell-mediated hepatitis. We found
      an up-regulation of hepatic EBI3 and p28 expression and augmented levels of IL-27
      in wild-type mice after ConA administration, suggesting a potential pathogenic
      role of this cytokine in ConA hepatitis. Consistently, IL-27 EBI3-deficient mice
      were almost completely protected from ConA-induced liver damage. Such protection
      was associated with reduced levels of IFN-gamma and its signaling proteins pSTAT
      1 and T-bet. Finally, in vivo blockade of IL-27 function using a soluble IL-27
      receptor fusion protein led to reduced pSTAT1 levels and suppression of liver
      injury. Taken together, these data demonstrate a key pathogenic role of IL-27 in
      T cell-mediated liver injury. Furthermore, in vivo blockade of IL-27 emerges as a
      novel potential therapy for T cell-mediated hepatitis.

PMID- 18097000
TI  - Cutting edge: requirement for TRAF6 in the induction of T cell anergy.
AB  - TRAF6, TNFR-associated factor 6, is a key adaptor downstream from the TNF
      receptor and TLR superfamily members. T cell-specific deletion of TRAF6 (TRAF6
      DeltaT) was recently shown to result in the development of multiorgan
      inflammatory disease and the resistance of responder T cells to suppression by
      CD4+CD25+ regulatory T cells. In this study we examined the role of TRAF6 in an
      additional mechanism of peripheral tolerance, anergy. We have determined that the
      loss of TRAF6 restores the ability of CD28-/- T cells to proliferate and produce
      IL-2. Consistent with this, TRAF6-DeltaT T cells were resistant to anergizing
      signals both in vitro and in vivo. Resistance to anergy was correlated with
      decreased expression of Cbl-b. These findings reveal that in addition to its role
      in rendering T cells susceptible to control by CD4+CD25+ regulatory T cells,
      TRAF6 is essential for the induction of T cell anergy, implicating TRAF6 as a
      critical mediator of peripheral tolerance.

PMID- 18097001
TI  - Cutting edge: Guillain-Barre syndrome-associated IgG responses to gangliosides
      are generated independently of CD1 function in mice.
AB  - CD1 molecules present a variety of microbial glycolipids and self-glycolipids to
      T cells, but their potential role in humoral responses to glycolipid Ags remains
      to be established. To address this issue directly, we used GM1/GD1a-deficient
      mice, which, upon immunization with heat-killed Campylobacter jejuni, develop
      Guillain-Barre syndrome-associated IgG Abs against the GM1/GD1a sugar chain
      epitopes of bacterial lipo-oligosaccharides (LOS). Our results showed that anti
      ganglioside Abs of the IgG1, IgG2b, and IgG3 isotypes were produced in the
      absence of group 2 CD1 (CD1d) expression. Unlike mouse and human group 2 CD1
      molecules that specifically bound LOS, none of the group 1 CD1 molecules (CD1a,
      CD1b, and CD1c in humans) were capable of interacting with LOS. Thus, these
      results indicate CD1-independent pathways for anti-ganglioside Ab production.

PMID- 18097002
TI  - Cutting edge: mechanism of enhancement of in vivo cytokine effects by anti
      cytokine monoclonal antibodies.
AB  - Inhibitory anti-cytokine mAbs are used to treat cytokine-mediated disorders.
      Recently, however, S4B6, an anti-IL-2 mAb that blocks IL-2 binding to IL-2Ralpha,
      a receptor component that enhances affinity but is not required for signaling,
      was shown to enhance IL-2 agonist effects in vivo. We evaluated how S4B6 enhances
      IL-2 effects and whether a similar mechanism allows mAbs to IL-4 to enhance IL-4
      effects. Induction of T cell proliferation by IL-2/S4B6 complexes did not require
      complex dissociation and was IL-2Ralpha independent. S4B6 increased IL-2 agonist
      effects by increasing in vivo half-life, not by focusing IL-2 onto cells through
      Fc receptors. In contrast to IL-2/S4B6 complexes, anti-IL-4 mAb enhancement of in
      vivo IL-4 effects required IL-4/anti-IL-4 mAb complex dissociation. Thus, agonist
      effects observed with high doses of anti-IL-2 mAb are most likely only applicable
      for mAbs that maintain cytokine half-life without blocking binding to receptor
      signaling components.

PMID- 18097003
TI  - TNF-alpha is critical to facilitate hemopoietic stem cell engraftment and
      function.
AB  - The use of tolerogenic cells as an approach to induce tolerance to solid organ
      allografts is being aggressively pursued. A major limitation to the clinical
      application of cell-based therapies has been the ability to obtain sufficient
      numbers and also preserve their tolerogenic state. We previously reported that
      small numbers of bone marrow-derived CD8+/TCR- graft facilitating cells (FC)
      significantly enhance hemopoietic stem cell (HSC) engraftment in allogeneic and
      syngeneic recipients. Although the majority of FC resemble precursor plasmacytoid
      dendritic cells (p-preDC), p-preDC do not replace FC in facilitating function. In
      the present studies, we investigated the mechanism of FC function. We show for
      the first time that FC significantly enhance HSC clonogenicity, increase the
      proportion of multipotent progenitors, and prevent apoptosis of HSC. These
      effects require direct cell:cell contact between FC and HSC. Separation of FC
      from HSC by transwell membranes completely abrogates the FC effect on HSC. p
      preDC FC do not replace FC total in these effects on HSC function. FC produce TNF
      alpha, and FC from TNF-alpha-deficient mice exhibit impaired facilitation in vivo
      and loss of the in vitro effects on HSC. Neutralizing TNF-alpha in FC similarly
      blocks the FC effect. The antiapoptotic effect of FC is associated with up
      regulation of Bcl-3 transcripts in HSC and blocking of TNF-alpha is associated
      with abrogation of up-regulation of Bcl-3 transcripts. These data demonstrate a
      critical role for TNF-alpha in mediating FC function. FC may have a significant
      impact upon the safe use of chimerism to establish tolerance to transplanted
      organs and tissue.

PMID- 18097004
TI  - A Th1-recognized peptide P277, when tandemly repeated, enhances a Th2 immune
      response toward effective vaccines against autoimmune diabetes in nonobese
      diabetic mice.
AB  - Subunit immunogens containing tandemly repeated copies of T and B cell epitopes
      have been shown to be more immunogenic than the respective immunogen containing
      only a single copy of the sequence. To investigate whether the increased copies
      of the Th2-activated peptide sequence will enhance the Th2-like immune response,
      we compared the cytokine secreted in mice that inoculated with two immunogens
      containing one or six tandemly repeated copies of a Th2-activated peptide
      sequence P277. Immunization of mice with a 6xP277 fusion protein elicited much
      higher levels of Th2-type cytokines and lower Th1-type cytokines than with a
      fusion protein with one P277 peptide. The data of tandemly repeated peptide P277
      potentiate the anti-inflammatory in NOD mice, most likely associated with a Th1
      to Th2 cytokine shift specific for the autoimmune T cells, which suggested that
      application of multiple tandem repeats of a Th2-activated epitope is an efficient
      method to enhance the anti-inflammatory immune response by shifting the immune
      response from Th1-like to Th2-like. The subunit immunogens containing tandemly
      repeated copies of peptide P277 might be effective vaccines against autoimmune
      diabetes in NOD mice.

PMID- 18097005
TI  - Memory CD8+ T cell responses expand when antigen presentation overcomes T cell
      self-regulation.
AB  - Antimicrobial memory CD8+ T cell responses are not readily expanded by either
      repeated infections or immunizations. This is a major obstacle to the development
      of T cell vaccines. Prime-boost immunization with heterologous microbes sharing
      the same CD8+ epitope can induce a large expansion of the CD8+ response; however,
      different vectors vary greatly in their ability to boost for reasons that are
      poorly understood. To investigate how efficient memory T cell expansion can
      occur, we evaluated immune regulatory events and Ag presentation after secondary
      immunization with strong and weak boosting vectors. We found that dendritic cells
      were essential for T cell boosting and that Ag presentation by these cells was
      regulated by cognate memory CD8+ T cells. When weak boosting vectors were used
      for secondary immunization, pre-established CD8+ T cells were able to effectively
      curtail Ag presentation, resulting in limited CD8+ T cell expansion. In contrast,
      a strong boosting vector, vaccinia virus, induced highly efficient Ag
      presentation that overcame regulation by cognate T cells and induced large
      numbers of memory CD8+ T cells to expand. Thus, efficient targeting of Ag to
      dendritic cells in the face of cognate immunity is an important requirement for T
      cell expansion.

PMID- 18097006
TI  - Immunotherapy with chimeric NKG2D receptors leads to long-term tumor-free
      survival and development of host antitumor immunity in murine ovarian cancer.
AB  - Ovarian cancer is one of the leading causes of cancer death in women and the
      development of novel therapies is needed to complement the standard treatment
      options such as chemotherapy and radiation. In this study, we show that treatment
      with T cells expressing a chimeric NKG2D receptor (chNKG2D) was able to lead to
      long-term, tumor-free survival in mice bearing established ovarian tumors. Tumor
      free mice were able to reject a rechallenge with ovarian tumor cells 225 days
      after original tumor injection. In addition, chNKG2D T cell treatment induced
      specific host immune responses to ovarian tumor cells, including the development
      of both CD8+ and CD4+ T cell tumor-specific memory responses. The chNKG2D T cells
      reduced the ovarian tumor burden using both cytotoxic and cytokine-dependent
      pathways. Specifically, chNKG2D T cell expression of perforin, GM-CSF, and IFN
      gamma were essential for complete antitumor efficacy.

PMID- 18097007
TI  - HIV-1 Tat suppresses gp120-specific T cell response in IL-10-dependent manner.
AB  - A large number of multicomponent vaccine candidates are currently in clinical
      evaluation, many of which also include the HIV-1 Tat protein, an important
      regulatory protein of the virus. However, whether Tat, a known immune effector
      molecule with a well-conserved sequence among different HIV subtypes, affects the
      immune response to a coimmunogen is not well understood. In this study, using a
      bicistronic vector expressing both gp120 and Tat, we have analyzed the role of
      Tat in elicitation of the gp120-specific immune response. The T cell responses to
      gp120 were greatly diminished in mice coimmunized with Tat as compared with mice
      immunized with gp120 alone. This immunosuppressive activity of Tat was not
      confined to viral Ag only because it also suppressed the immune response of
      unrelated Ag. Analysis of the cytokine profile suggests that Tat induces IL-10
      and since IL-10 has been demonstrated to have appreciable T cell inhibitory
      activity, it is plausible that IL-10 could be responsible for Tat-mediated
      immunosuppression. Finally, the immunosuppressive effect of Tat was not observed
      in IL-10-deficient mice, confirming the role of IL-10 in Tat-mediated
      immunosuppression. Thus, our results demonstrate for the first time that the
      immunosuppressive effect of Tat is mediated through IL-10 and suggests that Tat
      induced IL-10-mediated immune suppression seems to cripple immune surveillance
      during HIV-1 infection.

PMID- 18097008
TI  - Ex vivo rapamycin generates apoptosis-resistant donor Th2 cells that persist in
      vivo and prevent hemopoietic stem cell graft rejection.
AB  - Because ex vivo rapamycin generates murine Th2 cells that prevent Graft-versus
      host disease more potently than control Th2 cells, we hypothesized that rapamycin
      would generate Th2/Tc2 cells (Th2/Tc2.R cells) that abrogate fully MHC-disparate
      hemopoietic stem cell rejection more effectively than control Th2/Tc2 cells. In a
      B6-into-BALB/c graft rejection model, donor Th2/Tc2.R cells were indeed enriched
      in their capacity to prevent rejection; importantly, highly purified CD4+ Th2.R
      cells were also highly efficacious for preventing rejection. Rapamycin-generated
      Th2/Tc2 cells were less likely to die after adoptive transfer, accumulated in
      vivo at advanced proliferative cycles, and were present in 10-fold higher numbers
      than control Th2/Tc2 cells. Th2.R cells had a multifaceted, apoptosis-resistant
      phenotype, including: 1) reduced apoptosis after staurosporine addition, serum
      starvation, or CD3/CD28 costimulation; 2) reduced activation of caspases 3 and 9;
      and 3) increased anti-apoptotic Bcl-xL expression and reduced proapoptotic Bim
      and Bid expression. Using host-versus-graft reactivity as an immune correlate of
      graft rejection, we found that the in vivo efficacy of Th2/Tc2.R cells 1) did not
      require Th2/Tc2.R cell expression of IL-4, IL-10, perforin, or Fas ligand; 2)
      could not be reversed by IL-2, IL-7, or IL-15 posttransplant therapy; and 3) was
      intact after therapy with Th2.R cells relatively devoid of Foxp3 expression. We
      conclude that ex vivo rapamycin generates Th2 cells that are resistant to
      apoptosis, persist in vivo, and effectively prevent rejection by a mechanism that
      may be distinct from previously described graft-facilitating T cells.

PMID- 18097009
TI  - Requirement of calcineurin a beta for the survival of naive T cells.
AB  - Calcineurin (Cn) is a Ca2+/calmodulin-dependent phosphatase that dephosphorylates
      and activates NFAT, a transcription factor essential for T cell activation. T
      lymphocytes predominantly express the calcineurin Abeta (CnAbeta) isoform, and
      the deletion of the CnAbeta gene results in defective T cell proliferation and IL
      2 production in response to TCR stimulation. In this study, we show that CnAbeta
      enhances the spontaneous survival of naive T cells by maintaining high levels of
      Bcl-2, a critical homeostatic survival factor for naive T cells. T cells obtained
      from CnAbeta-/- mice displayed accelerated spontaneous apoptosis. The observed
      apoptosis of the CnAbeta-/- T cells was prevented by IL-7 and IL-15, two
      cytokines critical for the homeostatic survival of naive T cells. Furthermore,
      CD4+ or CD8+ single positive CnAbeta-/- thymocytes also underwent accelerated
      apoptosis. However, no obvious difference in the apoptosis of CD4+CD8+ double
      positive thymocytes was observed between CnAbeta-/- and wild-type mice,
      suggesting a specific function of CnAbeta in the survival of single positive T
      cells. Bcl-2 levels were found to be significantly lower in CnAbeta-/- T cells.
      Transgenic expression of Bcl-xL restored the survival of the CnAbeta-/- T cells.
      Thus, in addition to its role in mediating TCR signals essential for T cell
      activation, CnAbeta is also required for the homeostatic survival of naive T
      cells.

PMID- 18097010
TI  - Bystander central memory but not effector memory CD8+ T cells suppress allograft
      rejection.
AB  - Memory T cells respond faster and more vigorously than their naive counterparts
      and are critical for adaptive immunity. However, it is unknown whether and how
      memory T cells react in the face of irrelevant Ags. It is generally accepted that
      bystander memory T cells are neutral in immune responsiveness. In this study, we
      present the first evidence that bystander central memory (TCM), but not effector
      memory (TEM), CD8+ T cells suppress allograft rejection as well as T cell
      proliferation in the draining lymph nodes (DLN) of recipient mice. Both bystander
      TCM and naive T cells, but fewer TEM cells, migrated to DLN, whereas TCM cells
      exhibited faster turnover than their naive counterparts, suggesting that
      bystander TCM cells have an advantage over their naive counterparts in
      suppression. However, bystander TEM cells migrated to inflammatory graft sites,
      but not DLN, and yet failed to exert their suppression. These findings indicate
      that bystander memory T cells need to migrate to lymph nodes to exert their
      suppression by inhibiting responder T cell activation or homeostatic
      proliferation. Moreover, the suppression mediated by bystander TCM cells was
      largely dependent on IL-15, as IL-15 was required for their homeostatic
      proliferation and TCM-mediated suppression of allograft rejection. This
      suppression also required the presence of TGFbeta1, as TCM cells expressed
      TGFbeta1 while neutralizing TGFbeta1 abolished their suppression. Thus, bystander
      TCM, but not TEM, CD8+ T cells are potent suppressors rather than bystanders.
      This new finding will have an impact on cellular immunology and may have clinic
      implications for tolerance induction.

PMID- 18097011
TI  - Human Th17 cells share major trafficking receptors with both polarized effector T
      cells and FOXP3+ regulatory T cells.
AB  - It is a question of interest whether Th17 cells express trafficking receptors
      unique to this Th cell lineage and migrate specifically to certain tissue sites.
      We found several Th17 cell subsets at different developing stages in a human
      secondary lymphoid organ (tonsils) and adult, but not in neonatal, blood. These
      Th17 cell subsets include a novel in vivo-stimulated tonsil IL17+ T cell subset
      detected without any artificial stimulation in vitro. We investigated in depth
      the trafficking receptor phenotype of the Th17 cell subsets in tonsils and adult
      blood. The developing Th17 cells in tonsils highly expressed both Th1- (CCR2,
      CXCR3, CCR5, and CXCR6) and Th2-associated (CCR4) trafficking receptors.
      Moreover, Th17 cells share major non-lymphoid tissue trafficking receptors, such
      as CCR4, CCR5, CCR6, CXCR3, and CXCR6, with FOXP3+ T regulatory cells. In
      addition, many Th17 cells express homeostatic chemokine receptors (CD62L, CCR6,
      CCR7, CXCR4, and CXCR5) implicated in T cell migration to and within lymphoid
      tissues. Expression of CCR6 and CCR4 by some Th17 cells is not a feature unique
      to Th17 cells but shared with FOXP3+ T cells. Interestingly, the IL17+IFN-gamma+
      Th17 cells have the features of both IL17-IFN-gamma+ Th1 and IL17+IFN-gamma- Th17
      cells in expression of trafficking receptors. Taken together, our results
      revealed that Th17 cells are highly heterogeneous, in terms of trafficking
      receptors, and programmed to share major trafficking receptors with other T cell
      lineages. These findings have important implications in their distribution in the
      human body in relation to other regulatory T cell subsets.

PMID- 18097012
TI  - Distinct role for CD8 T cells toward cutaneous tumors and visceral metastases.
AB  - The growth of immunogenic tumors in immunocompetent individuals is one of the
      oldest conundrums in tumor immunology. Although the ability of mouse CD8+ T cells
      to control transplanted tumors is well documented, little is known about their
      impact on autochthonous tumors. To gain insight into the role of CD8+ T cells
      during the course of cancer development, we produced a novel model of spontaneous
      melanoma. The metallothionein (MT)-ret/AAD mouse is transgenic for the RET
      oncogene and the chimeric MHC molecule AAD (alpha1-alpha2 domains of HLA-A2
      linked to alpha3 domain of H2-Dd). This model recapitulates the natural history
      of human melanoma, and expression of the AAD molecule makes it suitable for
      analyzing CD8+ T cell responses directed against peptide Ags that have been
      previously identified in HLA-A2+ melanoma patients. We found that, as tumors
      grow, mice develop a broad melanoma-specific CD8+ T cell response. Occurrence of
      cutaneous nodules is not affected by CD8+ T cell depletion, showing that although
      CD8+ T cells are functional, they have no effect on established cutaneous tumors.
      However, depleted mice die from visceral disease much earlier than controls,
      showing that CD8+ T cells control metastasis spreading and disease progression.
      Antigenic modulation is observed in visceral metastases, suggesting that visceral
      nodules may be subject to immunoediting. Our data demonstrate that growth of
      melanoma in the MT-ret/AAD model involves several tolerance mechanisms
      sequentially. They also reveal a different role for CD8+ T cells toward early
      stage of cutaneous tumors and late visceral metastatic stage of the disease.

PMID- 18097014
TI  - Experience-driven development: effector/memory-like alphaE+Foxp3+ regulatory T
      cells originate from both naive T cells and naturally occurring naive-like
      regulatory T cells.
AB  - Naturally occurring Foxp3+CD25+CD4+ regulatory T cells (Treg) have initially been
      described as anergic cells; however, more recent in vivo studies suggest that
      Tregs vigorously proliferate under both homeostatic as well as inflammatory
      conditions. We have previously identified a subset of murine CD4+ Tregs, which is
      characterized by expression of the integrin alphaEbeta7 and which displays an
      effector/memory-like phenotype indicative of Ag-specific expansion and
      differentiation. In the present study, the alphaE+ Treg subset was found to
      contain a large fraction of cycling cells under homeostatic conditions in healthy
      mice. Using an adoptive transfer system of Ag-specific T cells, we could
      demonstrate that the vast majority of transferred natural, naive-like CD25+CD4+
      Tregs acquired expression of the integrin alphaEbeta7 upon tolerogenic
      application of Ag via the oral route. In addition, using the same system, Foxp3+
      Tregs could be de novo induced from conventional naive CD25-CD4+ T cells, and
      this conversion was associated with concomitant expression of alphaE. These
      findings suggest that Tregs expressing the integrin alphaE are effector/memory
      Tregs with a high turnover rate that can develop in the periphery upon Ag contact
      under tolerogenic conditions, both from thymic-derived CD25+CD4+ Tregs with a
      naive-like phenotype as well as from conventional naive T cells.

PMID- 18097013
TI  - Retinoids accelerate B lineage lymphoid differentiation.
AB  - Retinoids are known to have potent effects on hemopoietic stem cell integrity,
      and our objective was to learn whether they influence cells destined to replenish
      the immune system. Total CD19+ B lineage cells increased substantially in the
      marrow and spleens of all-trans retinoic acid (ATRA)-treated C57BL6 mice, while
      lymphoid progenitors were reduced. All B lymphoid progenitors were targets of
      ATRA in culture and overall cell yields declined without reductions in
      proliferation. Remarkably, ATRA shortened the time required for primitive
      progenitors to generate CD19+ cells. PCR analysis and a panel of retinoid acid
      receptor (RAR)/retinoid X receptor agonist treatments suggested that RARalpha
      mediates these responses. The transcription factors EBF1 and Pax-5 were elevated
      during treatment and ATRA had similar effects on human B cell differentiation.
      That is, it inhibited the expansion of human progenitor cells and accelerated
      their differentiation to B lineage cells. There may be previously unsuspected
      side effects of ATRA therapy, and the new findings suggest retinoids can normally
      contribute to the lymphopoietic environment in bone marrow.

PMID- 18097015
TI  - Proliferating CD4+ T cells undergo immediate growth arrest upon cessation of TCR
      signaling in vivo.
AB  - To investigate the role of TCR signaling in the exit of CD4+ T cells from cell
      cycle, we took advantage of a low frequency TEa T cell adoptive transfer
      technique as well as the Y-Ae mAb to interrupt Ag/MHC recognition before the
      completion of clonal expansion. Termination of TCR signaling after 36 h of Ag
      exposure caused an immediate reduction in cell size and deceleration of G1->SG2M
      phase cell cycle progression. As a consequence, clonal expansion in the absence
      of durable TCR signaling decreased by two-thirds. Thus, CD4+ T cells scan for the
      presence Ag throughout their clonal expansion response, and continuously adjust
      their rate of cell growth and G1->S phase transition to match their intensity of
      TCR signaling.

PMID- 18097016
TI  - Sensitization of tumor cells to NK cell-mediated killing by proteasome
      inhibition.
AB  - Bortezomib is a proteasome inhibitor that has direct antitumor effects. We and
      others have previously demonstrated that bortezomib could also sensitize tumor
      cells to killing via the death ligand, TRAIL. NK cells represent a potent
      antitumor effector cell. Therefore, we investigated whether bortezomib could
      sensitize tumor cells to NK cell-mediated killing. Preincubation of tumor cells
      with bortezomib had no effect on short-term NK cell killing or purified granule
      killing assays. Using a 24-h lysis assay, increases in tumor killing was only
      observed using perforin-deficient NK cells, and this increased killing was found
      to be dependent on both TRAIL and FasL, correlating with an increase in tumor Fas
      and DR5 expression. Long-term tumor outgrowth assays allowed for the detection of
      this increased tumor killing by activated NK cells following bortezomib treatment
      of the tumor. In a tumor purging assay, in which tumor:bone marrow cell mixtures
      were placed into lethally irradiated mice, only treatment of these mixtures with
      a combination of NK cells with bortezomib resulted in significant tumor-free
      survival of the recipients. These results demonstrate that bortezomib treatment
      can sensitize tumor cells to cellular effector pathways. These results suggest
      that the combination of proteasome inhibition with immune therapy may result in
      increased antitumor efficacy.

PMID- 18097017
TI  - Loss of IL-7R and IL-15R expression is associated with disappearance of memory T
      cells in respiratory tract following influenza infection.
AB  - Following influenza virus infection, memory CD8 T cells are found in both
      lymphoid and nonlymphoid organs, where they exhibit striking differences in
      survival. We have assessed persistence, phenotype, and function of memory CD8 T
      cells expressing the same TCR in the airways, lung parenchyma, and spleen
      following influenza virus infection in mice. In contrast to memory CD8 T cells in
      the spleen, those residing in the airways gradually lost expression of IL-7R and
      IL-15R, did not respond to IL-7 and/or IL-15, and exhibited poor survival both in
      vivo and in vitro. Following adoptive transfer into the airways, splenic memory
      CD8 T cells also down-regulated IL-7R and IL-15R expression and failed to undergo
      homeostatic proliferation. Thus, although cytokines IL-7 and IL-15 play an
      essential role in memory CD8 T cell homeostasis in lymphoid organs, the levels of
      IL-7R and IL-15R expression likely set a threshold for the homeostatic regulation
      of memory CD8 T cells in the airways. These findings provide a molecular
      explanation for the gradual loss of airway memory CD8 T cells and heterosubtypic
      immunity following influenza infection.

PMID- 18097018
TI  - Early effector T cells producing significant IFN-gamma develop into memory.
AB  - Currently, transition of T cells from effector to memory is believed to occur as
      a consequence of exposure to residual suboptimal Ag found in lymphoid tissues at
      the waning end of the effector phase and microbial clearance. This led to the
      interpretation that memory arises from slightly activated late effectors
      producing reduced amounts of IFN-gamma. In this study, we show that CD4 T cells
      from the early stage of the effector phase in which both the Ag and activation
      are optimal also transit to memory. Moreover, early effector T cells that have
      undergone four divisions expressed significant IL-7R, produced IFN-gamma, and
      yielded rapid and robust memory responses. Cells that divided three times that
      had marginal IL-7R expression and no IFN-gamma raised base level homeostatic
      memory, whereas those that have undergone only two divisions and produced IFN
      gamma yielded conditioned memory despite low IL-7R expression. Thus, highly
      activated early effectors generated under short exposure to optimal Ag in vivo
      develop into memory, and such transition is dependent on a significant production
      of the cell's signature cytokine, IFN-gamma.

PMID- 18097020
TI  - CD62L (L-selectin) down-regulation does not affect memory T cell distribution but
      failure to shed compromises anti-viral immunity.
AB  - The down-regulation of CD62L that accompanies T lymphocyte activation is thought
      to redirect cells away from lymph nodes to sites of infection. In this study,
      CD62L was maintained on Ag-activated T cells and their distribution, and ability
      to clear pathogen from peripheral sites determined. CD62L was down-regulated on
      Ag-specific CD8 T cells in lungs of C57BL/6 mice but maintained in CD62L
      transgenic mice at day 8 after influenza infection. However, the numbers of
      influenza-specific CD8 T cells recruited were similar in CD62L transgenic and
      C57BL/6 mice. Memory CD8 T cell numbers in the lungs and noninvolved organs 100
      days after primary infection were similar in CD62L transgenic and C57BL/6 mice,
      despite differing CD62L expression. Transgenic mice expressing wild-type CD62L
      cleared a recombinant vaccinia virus expressing an influenza-derived CD8 T cell
      epitope as efficiently as C57BL/6 mice. However, transgenic mice expressing a
      protease resistant mutant of CD62L showed significantly delayed viral clearance,
      despite normal CTL generation and the presence of CD107a and IFN-gamma expressing
      influenza-specific CD8 T cells. These results demonstrate that CD62L down
      regulation is not required for CD8 memory cells to home to sites of infection.
      However, their ability to clear virus is significantly compromised if CD62L
      shedding is abrogated.

PMID- 18097019
TI  - Baculovirus-infected insect cells expressing peptide-MHC complexes elicit
      protective antitumor immunity.
AB  - Evaluation of T cell responses to tumor- and pathogen-derived peptides in
      preclinical models is necessary to define the characteristics of efficacious
      peptide vaccines. We show in this study that vaccination with insect cells
      infected with baculoviruses expressing MHC class I linked to tumor peptide
      mimotopes results in expansion of functional peptide-specific CD8+ T cells that
      protect mice from tumor challenge. Specific peptide mimotopes selected from
      peptide-MHC libraries encoded by baculoviruses can be tested using this vaccine
      approach. Unlike other vaccine strategies, this vaccine has the following
      advantages: peptides that are difficult to solublize can be easily characterized,
      bona fide peptides without synthesis artifacts are presented, and additional
      adjuvants are not required to generate peptide-specific responses. Priming of
      antitumor responses occurs within 3 days of vaccination and is optimal 1 wk after
      a second injection. After vaccination, the Ag-specific T cell response is similar
      in animals primed with either soluble or membrane-bound Ag, and CD11c+ dendritic
      cells increase expression of maturation markers and stimulate proliferation of
      specific T cells ex vivo. Thus, the mechanism of Ag presentation induced by this
      vaccine is consistent with cross-priming by dendritic cells. This straightforward
      approach will facilitate future analyses of T cells elicited by peptide
      mimotopes.

PMID- 18097021
TI  - Caspase-independent cell death by CD300LF (MAIR-V), an inhibitory immunoglobulin
      like receptor on myeloid cells.
AB  - The myeloid-associated Ig-like receptor family (CD300) consists of nine
      activating or inhibitory cell surface receptors preferentially expressed on
      myeloid cells and are encoded by the genes in a small cluster on mouse chromosome
      11. One of the receptors, CD300LF (MAIR-V), has a long cytoplasmic tail
      containing two consensus ITIMs and an immunoreceptor tyrosine-based switching
      motif, suggesting that CD300LF regulates the activation of myeloid cells.
      However, the functional characteristics of this receptor are still incompletely
      understood. In this study, we demonstrate that cross-linking CD300LF with anti
      CD300LF mAb induced cell death in peritoneal macrophages as well as in several
      transfectants expressing CD300LF. CD300LF-mediated cell death was dependent on
      the cytoplasmic region but did not require an ITIM or immunoreceptor tyrosine
      based switching motif. Scanning electron microscopy revealed a loss of blebs from
      the surface of the dead cells mediated by CD300LF, a morphological feature
      similar to that observed in apoptotic cells. However, CD300LF-mediated cell death
      was not inhibited by a caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp
      fluoromethylketone, or autophagy inhibitors, 3-methyladenine or N-acetyl-L
      cystein. Moreover, the splicing isoform of a transcription factor, X-box binding
      protein-1, which is produced in dead cells as a response to endoplasmic reticulum
      stress, was not detected. Together, these results indicate that CD300LF mediates
      caspase and endoplasmic reticulum stress-independent cell death by a novel
      mechanism.

PMID- 18097022
TI  - Human T cells that are able to produce IL-17 express the chemokine receptor CCR6.
AB  - Some pathways of T cell differentiation are associated with characteristic
      patterns of chemokine receptor expression. A new lineage of effector/memory CD4+
      T cells has been identified whose signature products are IL-17 cytokines and
      whose differentiation requires the nuclear receptor, RORgammat. These Th17 cells
      are critical effectors in mouse models of autoimmune disease. We have analyzed
      the association between chemokine receptor expression and IL-17 production for
      human T cells. Activating cord blood (naive) CD4+ T cells under conditions
      driving Th17 differentiation led to preferential induction of CCR6, CCR9, and
      CXCR6. Despite these data, we found no strong correlation between the production
      of IL-17 and expression of CCR9 or CXCR6. By contrast, our analyses revealed that
      virtually all IL-17-producing CD4+ T cells, either made in our in vitro cultures
      or found in peripheral blood, expressed CCR6, a receptor found on approximately
      50% of CD4+ memory PBL. Compared with CD4+CD45RO+CCR6- cells, CD4+CD45RO+CCR6+
      cells contained at least 100-fold more IL-17A mRNA and secreted 100-fold more IL
      17 protein. The CCR6+ cells showed a similar enrichment in mRNA for RORgammat.
      CCR6 was likewise expressed on all IL-17-producing CD8+ PBL. CCR6 has been
      associated with the trafficking of T, B, and dendritic cells to epithelial sites,
      but has not been linked to a specific T cell phenotype. Our data reveal a
      fundamental feature of IL-17-producing human T cells and a novel role for CCR6,
      suggesting both new directions for investigating IL-17-related immune responses
      and possible targets for preventing inflammatory injury.

PMID- 18097023
TI  - Nuclear export of NF90 to stabilize IL-2 mRNA is mediated by AKT-dependent
      phosphorylation at Ser647 in response to CD28 costimulation.
AB  - IL-2 is one of the most important cytokines required for T cell-mediated immune
      responses. Costimulation of CD28 in T cells up-regulates IL-2 mRNA levels via
      transcription activation and mRNA stabilization. Upon T cell activation, NF90, an
      AU-rich element (ARE)-binding protein, translocates from the nucleus into the
      cytoplasm, where it binds to the ARE-containing 3' untranslated regions of IL-2
      mRNA and slows down degradation of IL-2 mRNA. The translocation of NF90 is
      mediated through a nuclear export signal at its N terminus, but how it is
      triggered is still unclear. Phosphorylation of ARE-binding proteins has been
      reported as a signal transduction pathway to stabilize ARE-containing
      transcripts. In this study, we demonstrate that AKT phosphorylates NF90 on Ser647
      upon CD28 costimulation. This phosphorylation is necessary for nuclear export of
      NF90 and IL-2 mRNA stabilization by this protein, because a mutation at Ser647
      abolished both functions. We observed that treatment of cells with CD28
      costimulation induced distinct increase in phosphorylation of AKT and NF90 at
      Ser647 concomitantly. Phosphorylation at Ser647 of NF90 up-regulated IL-2
      production in response to CD28 costimulation. In vivo and in vitro data support a
      model in which CD28 costimulation activates AKT to phosphorylate NF90 at Ser647
      and phosphorylation triggers NF90 to relocate to the cytoplasm and stabilize IL-2
      mRNA.

PMID- 18097024
TI  - CD36 is differentially expressed on B cell subsets during development and in
      responses to antigen.
AB  - Of a number of mAbs made by immunization with sort-purified marginal zone (MZ) B
      cells, one was shown to recognize the mouse scavenger receptor CD36. Although
      CD36 is expressed by most resting MZ B cells and not by follicular and B1 B
      cells, it is rapidly induced on follicular B cells in vitro following TLR and
      CD40 stimulation. In response to T-independent and T-dependent Ag challenge, we
      found that CD36 was expressed on IgM+ plasma cells, but down-regulated on isotype
      switched plasma cells in vivo. Although development, localization, and phenotype
      of MZ B cells in CD36-/- mice appeared normal, there was a minor block in the
      transitional stages of mature B cell development. In both primary and secondary
      Ab responses to heat-killed Streptococcus pneumoniae (R36A strain), both
      phosphoryl choline (PC)-specific IgM and IgG levels in CD36-/- mice were slightly
      reduced compared with wild-type mice. In addition, mice deficient in both TLR2
      and CD36 produced significantly reduced levels of anti-PC IgG titers than those
      of single gene-deficient mice, suggesting that they may cooperate in an anti-PC
      Ab response. Collectively, these results show that CD36 does not affect the
      development of B cells, but modulates both primary and secondary anti-PC Ab
      responses during S. pneumoniae infection similarly to TLR2.

PMID- 18097027
TI  - Hyperacute rejection by anti-Gal IgG1, IgG2a, and IgG2b is dependent on
      complement and Fc-gamma receptors.
AB  - We have previously reported that anti-Gal-alpha1,3Gal (Gal) IgG3 mAbs mediate a
      classical complement-dependent hyperacute rejection (HAR), while anti-Gal IgG1
      mAbs mediate HAR that is dependent on complement, the Fc-gamma receptors
      FcgammaRII/III (CD32/CD16), and NK cells. IgG2a and IgG2b subclasses can activate
      complement and have FcgammaR binding properties in vitro. Whether these IgG
      subclasses can mediate HAR in vivo and the mechanisms by which they would do so
      are not known. In this study, we isolated spontaneous IgG switch mutants from an
      anti-Gal IgG1 hybridoma. In vitro complement-mediated hemolytic assays with mouse
      complement indicate that both anti-Gal IgG2a and IgG2b mAbs were more potent
      compared with the parent anti-Gal IgG1. In vivo administration of anti-Gal IgG2a
      and IgG2b mAbs into Gal-/- mice induced HAR of rat cardiac xenografts. HAR
      induced by anti-Gal IgG2a and IgG2b was dependent on complement activation and
      the presence of NK cells. Using FcgammaRIII-deficient (Gal-/-CD16-/-) recipients,
      we observed that HAR mediated by different anti-Gal IgG subclasses was variably
      dependent on FcgammaRIII, with IgG1>IgG2b>>IgG2a=IgG3. Using FcgammaRI-deficient
      (Gal-/-CD64-/-) recipients, we observed that HAR mediated by anti-Gal IgG1,
      IgG2a, and IgG2b, but not by anti-Gal IgG3, was dependent on FcgammaRI.
      Collectively, these studies demonstrate the necessity and sufficiency of
      complement in IgG3-mediated HAR and the necessity of both complement and
      FcgammaR, especially FcgammaRI, in IgG1-, IgG2a-, and IgG2b-mediated HAR.

PMID- 18097025
TI  - The inhibitory HVEM-BTLA pathway counter regulates lymphotoxin receptor signaling
      to achieve homeostasis of dendritic cells.
AB  - Proliferation of dendritic cells (DC) in the spleen is regulated by positive
      growth signals through the lymphotoxin (LT)-beta receptor; however, the
      countering inhibitory signals that achieve homeostatic control are unresolved.
      Mice deficient in LTalpha, LTbeta, LTbetaR, and the NFkappaB inducing kinase show
      a specific loss of CD8- DC subsets. In contrast, the CD8alpha- DC subsets were
      overpopulated in mice deficient in the herpesvirus entry mediator (HVEM) or B and
      T lymphocyte attenuator (BTLA). HVEM- and BTLA-deficient DC subsets displayed a
      specific growth advantage in repopulating the spleen in competitive replacement
      bone marrow chimeric mice. Expression of HVEM and BTLA were required in DC and in
      the surrounding microenvironment, although DC expression of LTbetaR was necessary
      to maintain homeostasis. Moreover, enforced activation of the LTbetaR with an
      agonist Ab drove expansion of CD8alpha- DC subsets, overriding regulation by the
      HVEM-BTLA pathway. These results indicate the HVEM-BTLA pathway provides an
      inhibitory checkpoint for DC homeostasis in lymphoid tissue. Together, the
      LTbetaR and HVEM-BTLA pathways form an integrated signaling network regulating DC
      homeostasis.

PMID- 18097026
TI  - Targeted deletion of fgl2 leads to impaired regulatory T cell activity and
      development of autoimmune glomerulonephritis.
AB  - Mice with targeted deletion of fibrinogen-like protein 2 (fgl2) spontaneously
      developed autoimmune glomerulonephritis with increasing age, as did wild-type
      recipients reconstituted with fgl2-/- bone marrow. These data implicate FGL2 as
      an important immunoregulatory molecule and led us to identify the underlying
      mechanisms. Deficiency of FGL2, produced by CD4+CD25+ regulatory T cells (Treg),
      resulted in increased T cell proliferation to lectins and alloantigens, Th 1
      polarization, and increased numbers of Ab-producing B cells following
      immunization with T-independent Ags. Dendritic cells were more abundant in fgl2-/
      mice and had increased expression of CD80 and MHCII following LPS stimulation.
      Treg cells were also more abundant in fgl2-/- mice, but their suppressive
      activity was significantly impaired. Ab to FGL2 completely inhibited Treg cell
      activity in vitro. FGL2 inhibited dendritic cell maturation and induced apoptosis
      of B cells through binding to the low-affinity FcgammaRIIB receptor.
      Collectively, these data suggest that FGL2 contributes to Treg cell activity and
      inhibits the development of autoimmune disease.

PMID- 18097028
TI  - Induction and evolution of cytomegalovirus-specific CD4+ T cell clonotypes in
      rhesus macaques.
AB  - CMV infection induces robust CD4+ T cell responses in immunocompetent hosts that
      orchestrate immune control of viral replication, dissemination, and disease. In
      this study, we characterized the clonotypic composition of CD4+ T cell
      populations specific for rhesus CMV (RhCMV) in chronically infected adult rhesus
      macaques (RM) and in juvenile RM undergoing primary RhCMV infection and
      subsequent secondary challenge with RhCMV. In adult RM with established chronic
      infection, RhCMV-specific CD4+ T cell populations exhibited stable, pauciclonal
      structures with skewed hierarchies dominated by two or three clonotypes. During
      primary infection, in contrast, the initial RhCMV-specific CD4+ T cell
      populations were highly polyclonal and progressive evolution to the chronic
      pattern manifest in adults occurred over the ensuing 2-3 years. Clear patterns of
      clonal succession were observed during this maturation process, such that
      clonotypes present in the acute phase were largely replaced over time. However,
      rechallenge with RhCMV expanded virus-specific CD4+ T cell clonotypes identified
      solely during acute infection. These findings indicate that, during persistent
      viral infection, substantial selection pressures and ongoing clonotype
      recruitment shape the specific CD4+ T cell repertoire and that rapidly exhausted
      or superseded clonotypes often remain within the memory T cell pool.

PMID- 18097029
TI  - Immune complex-bearing follicular dendritic cells deliver a late antigenic signal
      that promotes somatic hypermutation.
AB  - We reasoned that immune complex (IC)-bearing follicular dendritic cells (FDCs)
      promote somatic hypermutation (SHM). This hypothesis was tested in murine
      germinal center reactions induced in vitro by coculturing 6-day (4-hydroxy-3
      nitrophenyl) acetyl-primed but unmutated lambda+ B cells, chicken gamma-globulin
      (CGG) memory T cells, FDCs, and ICs (anti-CGG plus NP-CGG). Mutations in primed
      lambda+ B cells were obtained only when both FDCs and immunogen were present.
      FDCs alone promoted B cell survival and Ab production but there were no mutations
      without more immunogen. Moreover, the mutation rate was enhanced when FDCs were
      activated. Trapped ICs ranged from 200 to 500 A apart on FDC membranes and this
      correlated with the periodicity known to optimally signal BCRs. FDCs are unique
      in their ability to retain ICs for months and a second signal mediated by FDC-ICs
      appeared to be needed a week or more after immunization by immunogen persisting
      on FDCs. However, the time needed to detect extensive SHM could be reduced to 7
      days if ICs were injected together with memory T cells in vivo. In marked
      contrast, no mutations were apparent after 7 days in vivo if ICs were replaced by
      free Ag that would not load on FDCs until Ab was produced. The data suggest that
      specific Ab production leads to the following events: Ab encounters Ag and ICs
      are formed, ICs are trapped by FDCs, B cells are stimulated by periodically
      arranged Ag in ICs on FDCs, and this late antigenic signal promotes SHM.

PMID- 18097030
TI  - Differential microenvironment localization of effector and memory CD8 T cells.
AB  - CD8 T cells are critical for the clearance of intracellular pathogens. Upon
      infection, naive CD8 T cells differentiate into effector cells that target and
      eliminate infected cells. Following clearance of the pathogen, most effector
      cells die, although a small fraction survives to establish a memory population.
      Subsequent exposure to the same pathogen induces a rapid response of memory T
      cells and efficient elimination of the pathogen. Although much is known about the
      CD8 T cell response, the precise microenvironment location of effector and memory
      CD8 T cells in secondary lymphoid organs is not well characterized. In this
      study, we present an in situ analysis of the localization of effector and memory
      CD8 T cells during the murine immune response to lymphocytic choriomenginits
      virus. We identified the location of these cells using a transgenic mouse model
      system in which CD8 T cells are irreversibly tagged with yellow fluorescent
      protein (YFP) after activation. After infection, YFP+ CD8 T cells were initially
      observed within T cell zones. Later, these cells were found in the red pulp and a
      disruption of all CD8 T cell zones was observed. After resolution of the immune
      response, YFP+ memory CD8 T cells were observed primarily in T cells zones. Thus,
      in the spleens of mice, effector CD8 T cells localize to the red pulp and memory
      CD8 T cells localize to the T cell zones. Upon rechallenge, memory CD8 T cells
      rapidly proliferate and the secondary effector CD8 T cells are found in the red
      pulp.

PMID- 18097031
TI  - Sequential shrinkage and swelling underlie P2X7-stimulated lymphocyte
      phosphatidylserine exposure and death.
AB  - Patterns of change in cell volume and plasma membrane phospholipid distribution
      during cell death are regarded as diagnostic means of distinguishing apoptosis
      from necrosis, the former being associated with cell shrinkage and early
      phosphatidylserine (PS) exposure, whereas necrosis is associated with cell
      swelling and consequent lysis. We demonstrate that cell volume regulation during
      lymphocyte death stimulated via the purinergic receptor P2X7 is distinct from
      both. Within seconds of stimulation, murine lymphocytes undergo rapid shrinkage
      concomitant with, but also required for, PS exposure. However, within 2 min
      shrinkage is reversed and swelling ensues ending in cell rupture. P2X7-induced
      shrinkage and PS translocation depend upon K+ efflux via KCa3.1, but use a
      pathway of Cl- efflux distinct from that previously implicated in apoptosis.
      Thus, P2X7 stimulation activates a novel pathway of cell death that does not
      conform to those conventionally associated with apoptosis and necrosis. The mixed
      apoptotic/necrotic phenotype of P2X7-stimulated cells is consistent with a
      potential role for this death pathway in lupus disease.

PMID- 18097032
TI  - Increased antigen presentation efficiency by coupling antigens to MHC class I
      trafficking signals.
AB  - Genetic modification of vaccines by linking the Ag to lysosomal or endosomal
      targeting signals has been used to route Ags into MHC class II processing
      compartments for improvement of CD4+ T cell responses. We report in this study
      that combining an N-terminal leader peptide with an MHC class I trafficking
      signal (MITD) attached to the C terminus of the Ag strongly improves the
      presentation of MHC class I and class II epitopes in human and murine dendritic
      cells (DCs). Such chimeric fusion proteins display a maturation state-dependent
      subcellular distribution pattern in immature and mature DCs, mimicking the
      dynamic trafficking properties of MHC molecules. T cell response analysis in
      vitro and in mice immunized with DCs transfected with Ag-encoding RNA showed that
      MITD fusion proteins have a profoundly higher stimulatory capacity than wild-type
      controls. This results in efficient expansion of Ag-specific CD8+ and CD4+ T
      cells and improved effector functions. We used CMVpp65 and NY-ESO-1 Ags to study
      preformed immune responses in CMV-seropositive individuals and cancer patients.
      We show that linking these Ags to the MITD trafficking signal allows
      simultaneous, polyepitopic expansion of CD8+ and CD4+ T cells, resulting in
      distinct CD8+ T cell specificities and a surprisingly broad and variable Ag
      specific CD4+ repertoire in different individuals.

PMID- 18097033
TI  - Differential contribution of NFATc2 and NFATc1 to TNF-alpha gene expression in T
      cells.
AB  - The NFAT family transcription factors play crucial roles in immunological and
      other biological events; however, the functional differences among NFAT members
      have not been fully elucidated. This study investigated the relative contribution
      of NFATc2 and NFATc1 to the transactivation of cytokine genes in T cells. Ectopic
      expression of NFATc2 but not NFATc1, especially its short isoform, enhanced TNF
      alpha synthesis in human T cells at the gene transcription level, whereas both
      NFATs augmented IL-2 expression. In addition, a reduction of the shortest NFATc1
      isoform using RNA interference technology failed to suppress TNF-alpha
      expression. The promoter/enhancer activity of the NFAT-binding site in the TNF
      alpha gene was up-regulated by NFATc2 but not by NFATc1, whereas both NFATs
      associated similarly with this region. A study of mRNA expression using
      NFATc2/NFATc1 chimeric molecules revealed that the enhancing activity of NFAT on
      the TNF-alpha gene was lost by truncation of its C-terminal transactivation
      domain. In addition, this domain derived from NFATc2 behaved as a dominant
      negative against the NFAT site in TNF-alpha promoter-dependent transcriptional
      activity in T cells. We conclude that the C-terminal transactivation domain in
      NFAT is crucial for TNF-alpha gene expression in human T cells.

PMID- 18097034
TI  - Antigen-driven interactions with dendritic cells and expansion of Foxp3+
      regulatory T cells occur in the absence of inflammatory signals.
AB  - Foxp3+ regulatory T cells (Tregs) play a pivotal role in the maintenance of
      peripheral T cell tolerance and are thought to interact with dendritic cells (DC)
      in secondary lymphoid organs. We analyzed here the in vivo requirements for
      selective expansion of Ag-specific Treg vs CD4+CD25- effector T cells and
      engagement of Ag-specific Treg-DC interactions in secondary lymphoid organs.
      Using i.v. Ag delivery in the absence of inflammation, we found that
      CD4+CD25+Foxp3+ Tregs undergo vigorous expansion and accumulate whereas naive
      CD4+CD25-Foxp3- T cells undergo abortive activation. Quantifying directly the
      interactions between Tregs and CD11c+ DC, we found that Tregs establish cognate
      contacts with endogenous CD11c+ DC in spleen and lymph nodes at an early time
      point preceding their expansion. Importantly, we observed that as few as 10(3)
      Tregs selectively expanded by i.v. Ag injection are able to suppress B and T cell
      immune responses in mouse recipients challenged with the Ag. Our results
      demonstrate that Tregs are selectively mobilized by Ag recognition in the absence
      of inflammatory signals, and can induce thereafter potent tolerance to defined Ag
      targets.

PMID- 18097035
TI  - Macrophages driven to a novel state of activation have anti-inflammatory
      properties in mice.
AB  - Recurrent episodes of inflammation underlie numerous pathologies, notably those
      of inflammatory bowel diseases. In this study, we describe a population of
      macrophages in a novel state of activation that mitigates colitis in mice. The
      cells responsible for this effect, called IFN-gamma-stimulated monocyte-derived
      cells (IFNgamma-MdC), derive from mouse spleen, blood, and bone marrow monocytes
      and are distinguished from known macrophage populations by mode of generation,
      cell surface phenotype, and function. IFNgamma-MdC only arise when macrophages
      are cultivated in the presence of CD40L-expressing CD4+ T cells, M-CSF, and IFN
      gamma. IFNgamma-MdC express markers including F4/80, CD11b/c, CD86, and CD274;
      they are negative for CD4, CD8, Gr1, CD19, CD80, and CD207. Functionally,
      IFNgamma-MdC are defined by their capacity to enrich cocultured T cell
      populations for CD4+CD25+Foxp3+ regulatory cells; this enrichment, constituting
      up to 60% or more of residual lymphocytes, is attributed to an expansion, but
      also to a cell contact and caspase-dependent depletion of activated T cells. In
      mice, IFNgamma-MdC delivered i.v. traffic to gut-associated peripheral lymphoid
      tissues, including the mesenteric lymph nodes, Peyer's patches, and colonic
      mucosa, and promote the clinical and histological resolution of chronic colitis.
      We conclude that IFNgamma-MdC represent macrophages in a novel state of
      activation, possessing multiple T cell-suppressive effects with therapeutic
      potential for the treatment of autoimmune inflammation.

PMID- 18097037
TI  - Maintenance of long-lived plasma cells and serological memory despite mature and
      memory B cell depletion during CD20 immunotherapy in mice.
AB  - CD20 mAb-mediated B cell depletion is an effective treatment for B cell
      malignancies and some autoimmune diseases. However, the full effects of B cell
      depletion on natural, primary, and secondary Ab responses and the maintenance of
      Ag-specific serum Ig levels are largely unknown. The relationship between memory
      B cells, long-lived plasma cells, and long-lived humoral immunity also remains
      controversial. To address the roles of B cell subsets in the longevity of humoral
      responses, mature B cells were depleted in mice using CD20 mAb. Peritoneal B cell
      depletion reduced natural and Ag-induced IgM responses. Otherwise, CD20+ B cell
      depletion prevented humoral immune responses and class switching and depleted
      existing and adoptively transferred B cell memory. Nonetheless, B cell depletion
      did not affect serum Ig levels, Ag-specific Ab titers, or bone marrow Ab
      secreting plasma cell numbers. Coblockade of LFA-1 and VLA-4 adhesion molecules
      temporarily depleted long-lived plasma cells from the bone marrow. CD20+ B cell
      depletion plus LFA-1/VLA-4 mAb treatment significantly prolonged Ag-specific
      plasma cell depletion from the bone marrow, with a significant decrease in Ag
      specific serum IgG. Collectively, these results support previous claims that bone
      marrow plasma cells are intrinsically long-lived. Furthermore, these studies now
      demonstrate that mature and memory B cells are not required for maintaining bone
      marrow plasma cell numbers, but are required for repopulation of plasma cell
      deficient bone marrow. Thereby, depleting mature and memory B cells does not have
      a dramatic negative effect on preexisting Ab levels.

PMID- 18097038
TI  - Targeting HIV-1 Gag into the defective ribosomal product pathway enhances MHC
      class I antigen presentation and CD8+ T cell activation.
AB  - The main source for endogenous peptides presented by the MHC class I (MHC-I)
      pathway are de novo-synthesized proteins which are degraded via the ubiquitin
      proteasome pathway. Different MHC-I Ag pools can be distinguished: first, short
      lived defective ribosomal products, which are degraded in concert with or shortly
      after their synthesis, and, second, functional proteins that enter the standard
      protein life cycle. To compare the contribution of these two Ag sources to the
      generation of MHC-I-presented peptides, we established murine cell lines which
      express as a model Ag the HIV-1 Gag polyprotein fused to ubiquitin (Ub) carrying
      the epitope SIINFEKL (SL). Gag was expressed either in its wild-type form
      (UbMGagSL) or as a variant UbRGagSL harboring an N-end rule degron signal.
      Although UbRGagSL displayed wild-type protein stability, its inherent defective
      ribosomal products rate observed after proteasome shutdown was increased
      concomitant with enhanced presentation of the SL epitope. In addition, UbRGagSL
      induces enhanced T cell stimulation of SL-specific B3Z hybridoma cells as
      measured in vitro and of adoptively transferred TCR-transgenic OT-1 T cells in
      vivo. Furthermore, an elevated frequency of SL-specific T cells was detected by
      IFN-gamma ELISPOT after immunization of naive C57BL/6 mice with UbRGagSL/EL4
      cells. These results further underline the role of the defective ribosomal
      product pathway in adaptive immunity.

PMID- 18097036
TI  - IL-15 treatment during acute simian immunodeficiency virus (SIV) infection
      increases viral set point and accelerates disease progression despite the
      induction of stronger SIV-specific CD8+ T cell responses.
AB  - In this study, we examined the effect of in vivo treatment of acutely SIV
      infected Mamu-A*01+ rhesus macaques with IL-15. IL-15 treatment during acute
      infection increased viral set point by 3 logs and accelerated the development of
      simian AIDS in two of six animals with one developing early minimal lesion SIV
      meningoencephalitis. Although IL-15 induced a 2- to 3-fold increase in SIV
      specific CD8+ T cell and NK cell numbers at peak viremia and reduced lymph node
      (LN) SIV-infected cells, this had no impact on peak viremia and did not lower
      viral set point. At viral set point, however, activated SIV-specific CD8+ T cells
      and NK cells were reduced in the blood of IL-15-treated animals and LN SIV
      infected cells were increased. Week 30 LN from IL-15-treated animals had
      significantly increased Gag-specific CD8+ T cell numbers, whereas total cell,
      lymphocyte, and CD4+ T cell numbers were reduced. IL-15 treatment significantly
      reduced anti-SIV Ab concentrations at week 3 and viral set point. IL-15 increased
      Ki-67+CD4+ T cells at week 1 of treatment and reduced blood CCR5+ and CD45RA
      CD62L- CD4+ T cells. The frequency of day 7 Ki-67+CD4+ T cells strongly
      correlated with viral set point. These findings suggest that CD4+ T cell
      activation during acute infection determines subsequent viral set point and IL-15
      treatment by increasing such activation elevates viral set point. Finally, IL-15
      treated acutely SIV-infected primates may serve as a useful model to investigate
      the poorly understood mechanisms that control viral set point and disease
      progression in HIV infection.

PMID- 18097039
TI  - Systemic, but not intestinal, IL-7 is essential for the persistence of chronic
      colitis.
AB  - We previously demonstrated that IL-7 is produced by intestinal goblet cells and
      is essential for the persistence of colitis. It is well known, however, that
      goblet cells are decreased or depleted in the chronically inflamed mucosa of
      animal colitis models or human inflammatory bowel diseases. Thus, in this study,
      we assess whether intestinal IL-7 is surely required for the persistence of
      colitis using a RAG-1/2-/- colitis model induced by the adoptive transfer of
      CD4+CD45RBhigh T cells in combination with parabiosis system. Surprisingly, both
      IL-7-/-xRAG-1-/- and IL-7+/+xRAG-1-/- host mice developed colitis 4 wk after
      parabiosis to a similar extent of colitic IL-7+/+xRAG-1-/- donor mice that were
      previously transferred with CD4+CD45RBhigh T cells. Of note, although the number
      of CD4+ T cells recovered from the spleen or the bone marrow of IL-7-/-xRAG-1-/-
      host mice was significantly decreased compared with that of IL-7+/+xRAG-1-/- host
      mice, an equivalent number of CD4+ T cells was recovered from the lamina propria
      of both mice, indicating that the expansion of CD4+ T cells in the spleen or in
      the bone marrow is dependent on IL-7, but not in the lamina propria. Development
      of colitis was never observed in parabionts between IL-7+/+xRAG-1-/- host and
      noncolitic IL-7-/-xRAG-1-/- donor mice that were transferred with CD4+CD45RBhigh
      T cells. Collectively, systemic, but not intestinal, IL-7 is essential for the
      persistence of colitis, suggesting that therapeutic approaches targeting the
      systemic IL-7/IL-7R signaling pathway may be feasible in the treatment of
      inflammatory bowel diseases.

PMID- 18097040
TI  - Molecular design of the Calphabeta interface favors specific pairing of
      introduced TCRalphabeta in human T cells.
AB  - A promising approach to adoptive transfer therapy of tumors is to reprogram
      autologous T lymphocytes by TCR gene transfer of defined Ag specificity. An
      obstacle, however, is the undesired pairing of introduced TCRalpha- and TCRbeta
      chains with the endogenous TCR chains. These events vary depending on the
      individual endogenous TCR and they not only may reduce the levels of cell surface
      introduced TCR but also may generate hybrid TCR with unknown Ag specificities. We
      show that such hybrid heterodimers can be generated even by the pairing of human
      and mouse TCRalpha- and TCRbeta-chains. To overcome this hurdle, we have
      identified a pair of amino acid residues in the crystal structure of a TCR that
      lie at the interface of associated TCR Calpha and Cbeta domains and are related
      to each other by both a complementary steric interaction analogous to a "knob
      into-hole" configuration and the electrostatic environment. We mutated the two
      residues so as to invert the sense of this interaction analogous to a charged
      "hole-into-knob" configuration. We show that this inversion in the CalphaCbeta
      interface promotes selective assembly of the introduced TCR while preserving its
      specificity and avidity for Ag ligand. Noteworthily, this TCR modification was
      equally efficient on both a Mu and a Hu TCR. Our data suggest that this approach
      is generally applicable to TCR independently of their Ag specificity and
      affinity, subset distribution, and species of origin. Thus, this strategy may
      optimize TCR gene transfer to efficiently and safely reprogram random T cells
      into tumor-reactive T cells.

PMID- 18097041
TI  - Pro-IL-16 recruits histone deacetylase 3 to the Skp2 core promoter through
      interaction with transcription factor GABP.
AB  - Pro-IL-16 is a PDZ domain-containing protein expressed in T cells. Our previous
      work showed that upon activation of normal T cells, pro-IL-16 mRNA and protein
      are diminished in close correlation to the down-regulation of p27KIP1 protein. In
      addition, we showed that pro-IL-16 regulates the transcription of Skp2, the
      mechanism of which, however, remains elusive. In this study, we identified GA
      binding protein beta1 subunit (GABPbeta1) and histone deacetylase 3 (HDAC3) as
      binding partners of pro-IL-16. Interestingly, both GABPbeta1 and HDAC3 have
      canonical PDZ-binding motifs and specifically bind to the first and second PDZ
      domain of pro-IL-16, respectively. Heat shock cognate protein 70 (HSC70) also
      copurified with the GST-PDZ1-containing fragment but lacks a C-terminal PDZ
      binding motif, suggesting that it binds through a different mechanism. We further
      showed that pro-IL-16 is located in a GABP transcriptional complex bound to the
      Skp2 promoter. In addition, we demonstrated that HDAC activity is critical for
      pro-IL-16-induced cell cycle arrest. Taken altogether, these data suggest that
      pro-IL-16 forms a complex with GABPbeta1 and HDAC3 in suppressing the
      transcription of Skp2. Thus, this study has revealed a novel mechanism with which
      pro-IL-16 regulates T cell growth through the Skp2-p27KIP1 pathway.

PMID- 18097042
TI  - Regulation of human DAP10 gene expression in NK and T cells by Ap-1 transcription
      factors.
AB  - Human NKG2D/DAP10 is an activation receptor expressed by NK and subsets of T
      cells, whose ligands include MHC class I chain-related (MIC) protein A and
      protein B and UL16-binding proteins that are often up-regulated by stress or
      pathological conditions. DAP10 is required for NKG2D/DAP10 cell surface
      expression and signaling capacity. Little is known about the mechanisms that
      regulate DAP10 gene expression. We describe the existence of multiple
      transcriptional start sites upstream of DAP10 exon 1 and identify the location of
      the basic promoter upstream of these starting sites. The promoter is active in NK
      and CD8+ T cells, but not in CD4+ T cells. We demonstrate TCR-mediated up
      regulation of DAP10 transcription and found that a 40 bp region within the DAP10
      promoter, containing an Ap-1 binding site, is largely responsible for this
      increased transcription. Using pull-down and chromatin immunoprecipitation
      assays, we show that the DAP10 promoter interacts with Ap-1 transcription factors
      in primary CD8+ T and NK cells in vitro and in vivo. Overexpression of c-Jun or c
      Fos in NK and T cells led to enhanced DAP10 promoter activity and DAP10 protein
      expression. Taken together, our data indicate that Ap-1 is an important
      transcription factor for regulating DAP10 gene expression in human NK and T
      cells, and that Ap-1 plays a key role in the transactivation of DAP10 promoter
      following TCR stimulation.

PMID- 18097043
TI  - Lineage-specific transition of histone signatures in the killer cell Ig-like
      receptor locus from hematopoietic progenitor to NK cells.
AB  - The clonal distribution and stable expression of killer cell Ig-like receptor
      (KIR) genes is epigenetically regulated. To assess the epigenetic changes that
      occur during hemopoietic development we examined DNA methylation and chromatin
      structure of the KIR locus in early hemopoietic progenitor cells and major
      lymphocyte lineages. In hemopoietic progenitor cells, KIR genes exhibited the
      major hallmarks of epigenetic repression, which are dense DNA methylation,
      inaccessibility of chromatin to Micrococcus nuclease digest, and a repressive
      histone signature, characterized by strong H3K9 dimethylation and reduced H4K8
      acetylation. In contrast, KIR genes of NK cells showed active histone signatures
      characterized by absence of H3K9 dimethylation and presence of H4K8 acetylation.
      Histone modifications correlated well with the competence of different lymphocyte
      lineages to express KIR; whereas H4K8 acetylation was high in NK and CD8+ T
      cells, it was almost absent in CD4+ T cells and B cells and, in the latter case,
      replaced by H3K9 dimethylation. In KIR-competent lineages, active histone
      signatures were also observed in silent KIR genes and in this case found in
      combination with dense DNA methylation of the promoter and nearby regions. The
      study suggests a two-step model of epigenetic regulation in which lineage
      specific acquisition of euchromatic histone marks is a prerequisite for
      subsequent gene-specific DNA demethylation and expression of KIR genes.

PMID- 18097044
TI  - HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes
      simplex virus glycoprotein D.
AB  - Evidence obtained from both animal models and humans suggests that T cells
      specific for HSV-1 and HSV-2 glycoprotein D (gD) contribute to protective
      immunity against herpes infection. However, knowledge of gD-specific human T cell
      responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes
      identified to date. In this study, we screened the HSV-1 gD amino acid sequence
      for HLA-A*0201-restricted epitopes using several predictive computational
      algorithms and identified 10 high probability CD8+ T cell epitopes. Synthetic
      peptides corresponding to four of these epitopes, each nine to 10 amino acids in
      length, exhibited high-affinity binding in vitro to purified human HLA-A*0201
      molecules. Three of these four peptide epitopes, gD53-61, gD70-78, and gD278-286,
      significantly stabilized HLA-A*0201 molecules on T2 cell lines and are highly
      conserved among and between HSV-1 and HSV-2 strains. Consistent with this, in 33
      sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2
      seropositive healthy individuals, the most frequent and robust CD8+ T cell
      responses, assessed by IFN-gamma ELISPOT, CD107a/b cytotoxic degranulation, and
      tetramer assays, were directed mainly against gD53-61, gD70-78, and gD278-286
      epitopes. In addition, CD8+ T cell lines generated by gD53-61, gD70-78, and gD278
      286 peptides recognized infected target cells expressing native gD. Lastly, CD8+
      T cell responses specific to gD53-61, gD70-78, and gD278-286 epitopes were
      induced in HLA-A*0201 transgenic mice following ocular or genital infection with
      either HSV-1 or HSV-2. The functional gD CD8+ T cell epitopes described herein
      are potentially important components of clinical immunotherapeutic and
      immunoprophylactic herpes vaccines.

PMID- 18097045
TI  - TLR9 contributes to antiviral immunity during gammaherpesvirus infection.
AB  - The human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus and EBV
      cause important infections. As pathogenetic studies of the human infections are
      restricted, murine gammaherpesvirus 68 serves as a model to study
      gammaherpesvirus pathogenesis. TLRs are a conserved family of receptors detecting
      microbial molecular patterns. Among the TLRs, TLR9 recognizes unmethylated CpG
      DNA motifs present in bacterial and viral DNA. The aim of this study was to
      assess the role of TLR9 in gammaherpesvirus pathogenesis. Upon stimulation with
      murine gammaherpesvirus 68, Flt3L-cultured bone marrow cells (dendritic cells)
      from TLR9-/- mice secreted reduced levels of IL-12, IFN-alpha, and IL-6, when
      compared with dendritic cells from wild-type mice. Intranasal infection of TLR9-/
      and wild-type mice did not reveal any differences during lytic and latent
      infection. In contrast, when infected i.p., TLR9-/- mice showed markedly higher
      viral loads both during lytic and latent infection. Thus, we show for the first
      time that TLR9 is involved in gammaherpesvirus pathogenesis and contributes to
      organ-specific immunity.

PMID- 18097046
TI  - Suppression of lethal Plasmodium yoelii malaria following protective immunization
      requires antibody-, IL-4-, and IFN-gamma-dependent responses induced by
      vaccination and/or challenge infection.
AB  - Immunization with Plasmodium yoelii merozoite surface protein (PyMSP)-8 protects
      mice from lethal malaria but does not prevent infection. Using this merozoite
      surface protein-based vaccine model, we investigated vaccine- and infection
      induced immune responses that contribute to protection. Analysis of prechallenge
      sera from rPyMSP-8-immunized C57BL/6 and BALB/c mice revealed high and comparable
      levels of Ag-specific IgG, but differences in isotype profile and specificity for
      conformational epitopes were noted. As both strains of mice were similarly
      protected against P. yoelii, we could not correlate vaccine-induced responses
      with protection. However, passive immunization studies suggested that protection
      resulted from differing immune responses. Studies with cytokine-deficient mice
      showed that protection was induced by immunization of C57BL/6 mice only when IL-4
      and IFN-gamma were both present. In BALB/c mice, the absence of either IL-4 or
      IFN-gamma led to predictable shifts in the IgG isotype profile but did not reduce
      the magnitude of the Ab response induced by rPyMSP-8 immunization. Immunized IL-4
      /- BALB/c mice were solidly protected against P. yoelii. To our surprise,
      immunized IFN-gamma-/- BALB/c mice initially controlled parasite growth but
      eventually succumbed to infection. Analysis of cytokine production revealed that
      P. yoelii infection induced two distinct peaks of IFN-gamma that correlated with
      periods of controlled parasite growth in intact, rPyMSP-8-immunized BALB/c mice.
      Maximal parasite growth occurred during a period of sustained TGF-beta
      production. Combined, the data indicate that induction of protective responses by
      merozoite surface protein-based vaccines depends on IL-4 and IFN-gamma-dependent
      pathways and that vaccine efficacy is significantly influenced by host responses
      elicited upon infection.

PMID- 18097047
TI  - B cells promote resistance to heterosubtypic strains of influenza via multiple
      mechanisms.
AB  - Immunity to heterosubtypic strains of influenza is thought to be mediated
      primarily by memory T cells, which recognize epitopes in conserved proteins.
      However, the involvement of B cells in this process is controversial. We show in
      this study that influenza-specific memory T cells are insufficient to protect
      mice against a lethal challenge with a virulent strain of influenza in the
      absence of B cells. B cells contribute to protection in multiple ways. First,
      although non-neutralizing Abs by themselves do not provide any protection to
      challenge infection, they do reduce weight loss, lower viral titers, and promote
      recovery of mice challenged with a virulent heterosubtypic virus in the presence
      of memory T cells. Non-neutralizing Abs also facilitate the expansion of
      responding memory CD8 T cells. Furthermore, in cooperation with memory T cells,
      naive B cells also promote recovery from infection with a virulent heterosubtypic
      virus by generating new neutralizing Abs. These data demonstrate that B cells use
      multiple mechanisms to promote resistance to heterosubtypic strains of influenza
      and suggest that vaccines that elicit both memory T cells and Abs to conserved
      epitopes of influenza may be an effective defense against a wide range of
      influenza serotypes.

PMID- 18097049
TI  - Impaired phagosomal maturation in neutrophils leads to periodontitis in lysosomal
      associated membrane protein-2 knockout mice.
AB  - Inflammatory periodontal diseases constitute one of the most common infections in
      humans, resulting in the destruction of the supporting structures of the
      dentition. Circulating neutrophils are an essential component of the human innate
      immune system. We observed that mice deficient for the major lysosomal-associated
      membrane protein-2 (LAMP-2) developed severe periodontitis early in life. This
      development was accompanied by a massive accumulation of bacterial plaque along
      the tooth surfaces, gingival inflammation, alveolar bone resorption, loss of
      connective tissue fiber attachment, apical migration of junctional epithelium,
      and pathological movement of the molars. The inflammatory lesions were dominated
      by polymorphonuclear leukocytes (PMNs) apparently being unable to efficiently
      clear bacterial pathogens. Systemic treatment of LAMP-2-deficient mice with
      antibiotics prevented the periodontal pathology. Isolated PMNs from LAMP-2
      deficient mice showed an accumulation of autophagic vacuoles and a reduced
      bacterial killing capacity. Oxidative burst response was not altered in these
      cells. Latex bead and bacterial feeding experiments showed a reduced ability of
      the phagosomes to acquire an acidic pH and late endocytic markers, suggesting an
      impaired fusion of late endosomes-lysosomes with phagosomes. This study
      underlines the importance of LAMP-2 for the maturation of phagosomes in PMNs. It
      also underscores the requirement of lysosomal fusion events to provide sufficient
      antimicrobial activity in PMNs, which is needed to prevent periodontal disease.

PMID- 18097048
TI  - Neutrophils clear bacteria associated with parasitic nematodes augmenting the
      development of an effective Th2-type response.
AB  - Infection with the parasitic nematode Nippostrongylus brasiliensis induces a
      potent Th2 response; however, little is known about early stages of the innate
      response that may contribute to protective immunity. To examine early events in
      this response, chemokine expression in the draining lymph node was examined after
      N. brasiliensis inoculation. Pronounced increases of several chemokines,
      including CCL2, were observed. Compared with wild-type mice, elevations in a Gr
      1bright population in the draining lymph node was significantly decreased in CCL2
      /- mice after N. brasiliensis inoculation. Further flow cytometric and
      immunofluorescent analysis showed that in wild-type mice, Gr-1+ cells transiently
      entered and exited the draining lymph node shortly after N. brasiliensis
      inoculation. The Gr-1bright population was comprised of neutrophils expressing
      TGF-beta and TNF-alpha. Following Gr-1+ cell depletion, N. brasiliensis infection
      resulted in transient, but significantly increased levels of IFN-gamma, increased
      serum IgG2a, reduced Th2 cytokines and serum IgE, greatly increased mortality,
      and delayed worm expulsion. Furthermore, bacteria were readily detected in vital
      organs. Infection of Gr-1+ cell-depleted mice with N. brasiliensis larvae that
      were pretreated with antibiotics prevented bacterial dissemination, Th1
      inflammatory responses, and decreases in host survival. This study indicates that
      parasitic nematodes can be an important vector of potentially harmful bacteria,
      which is typically controlled by CCL2-dependent neutrophils that ensure the
      optimal development of Th2 immune responses and parasite resistance.

PMID- 18097050
TI  - TLR3 increases disease morbidity and mortality from vaccinia infection.
AB  - Innate immunity is required for effective control of poxvirus infections, but
      cellular receptors that initiate the host response to these DNA viruses remain
      poorly defined. Given this information and the fact that functions of TLRs in
      immunity to DNA viruses remain controversial, we investigated effects of TLR3 on
      pathogenesis of vaccinia virus, a prototype poxvirus. We used a recombinant
      strain Western Reserve vaccinia virus that expresses firefly luciferase to infect
      wild-type C57BL/6 and TLR3-/- mice through intranasal inoculation.
      Bioluminescence imaging showed that TLR3-/- mice had substantially lower viral
      replication in the respiratory tract and diminished dissemination of virus to
      abdominal organs. Mice lacking TLR3 had reduced disease morbidity, as measured by
      decreased weight loss and hypothermia after infection. Importantly, TLR3-/- mice
      also had improved survival relative to wild-type mice. Infected TLR3-/- mice had
      significantly reduced lung inflammation and recruitment of leukocytes to the
      lung. Mice lacking TLR3 also had lower levels of inflammatory cytokines,
      including IL-6, MCP-1, and TNF-alpha in serum and/or bronchoalveolar lavage
      fluid, but levels of IFN-beta did not differ between genotypes of mice. To our
      knowledge, our findings show for the first time that interactions between TLR3
      and vaccinia increase viral replication and contribute to detrimental effects of
      the host immune response to poxviruses.

PMID- 18097051
TI  - NF-kappaB signaling, elastase localization, and phagocytosis differ in HIV-1
      permissive and nonpermissive U937 clones.
AB  - To identify positive or negative factors for HIV-1 infectivity, clones from the
      U937 promonocytic cell line that express similar levels of CD4 and CXCR4, but
      differ in HIV-1 susceptibility, were compared. In contrast to HIV-1 permissive
      clone 10 (plus), nonpermissive clone 17 (minus) was adherent to coverslips coated
      with chemokines, was phagocytic, killed bacteria, and expressed human leukocyte
      elastase (HLE) in a granule-like compartment (HLEG) that was never detected at
      the cell surface (HLECS). In contrast to the minus clone, the plus clone
      expressed HLE on the cell surface and was adherent to coverslips coated with the
      HLECS ligands alpha1proteinase inhibitor (alpha1PI, alpha1antitrypsin) and the
      HIV-1 fusion peptide. The phosphorylation status of several important signaling
      proteins was studied at the single cell level. Tumor suppressor p53, NF-kappaB
      p65, and Akt were constitutively phosphorylated in the plus clone, but not in the
      minus clone. Surprisingly, both alpha1PI and LPS induced phosphorylation of NF
      kappaB p65 Ser-536 in both clones, but induced dephosphorylation of Ser-529 in
      the plus clone only. HIV-1 permissivity was conferred to the minus clone in a
      manner that required stimulation by both alpha1PI and LPS and was coincident to
      NF-kappaB p65 phosphorylation/dephosphorylation events as well as translocation
      of HLE to the cell surface. Even when stimulated, the minus clone exhibited
      greater reverse transcriptase activity, but less p24, than the plus clone.
      Results presented suggest that HIV-1 uptake and production efficiency are
      influenced by signaling profiles, receptor distribution, and the phagocytic
      capacity specific to the stage of differentiation of the CD4+ target cell.

PMID- 18097052
TI  - Neutrophil microbicides induce a pathogen survival response in community
      associated methicillin-resistant Staphylococcus aureus.
AB  - In recent years, there has been a dramatic increase in the incidence of community
      associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. MW2
      (pulsed-field type USA400), the prototype CA-MRSA strain, is highly virulent and
      has enhanced ability to evade killing by neutrophils. Although progress has been
      made, the molecular basis for enhanced virulence of CA-MRSA remains incompletely
      defined. To that end, we studied resistance of MW2 to key microbicides of human
      neutrophils. Hydrogen peroxide (H2O2), hypochlorous acid, and azurophilic granule
      proteins had significant bacteriostatic but limited staphylocidal activity toward
      MW2 under the conditions tested. An MW2-specific microarray revealed common
      changes in S. aureus gene expression following exposure to each microbicide, such
      as up-regulation of transcripts involved in gene regulation (e.g., saeRS and
      kdpDE) and stress response. Azurophilic granule proteins elicited the greatest
      number of changes in MW2 transcripts, including up-regulation of mRNAs encoding
      multiple toxins and hemolysins (e.g., hlgA, hlgB, hlgC, hla, lukS-PV, lukF-PV,
      sec4, and set17-26). Notably, H2O2 triggered up-regulation of transcripts related
      to heme/iron uptake (e.g., isdA, isdB, and isdCDEFsrtBisdG), and an isogenic
      isdAB-negative strain of MW2 had increased susceptibility to H2O2 (p<0.001) and
      human neutrophils (p<0.05) compared with the wild-type parental strain. These
      findings reveal a S. aureus survival response wherein Iron-regulated surface
      determinant (Isd) proteins are important for resistance to innate host defense.
      Collectively, the data provide an enhanced view of the mechanisms used by S.
      aureus to circumvent destruction by the innate immune system.

PMID- 18097053
TI  - Multichannel fluorescence spinning disk microscopy reveals early endogenous CD4 T
      cell recruitment in contact sensitivity via complement.
AB  - Contact sensitivity (CS) is one of the primary in vivo models of T cell-mediated
      inflammation. The presence of CS-initiating CD4 T lymphocytes at the time of
      challenge is essential for transfer and full development of the late phase CS
      inflammatory response. From this observation investigators have speculated that
      early recruitment of CD4 T cells to the site of challenge must occur. Moreover,
      there must be rapid synthesis/release and disappearance of an important mediator
      during the first hours after hapten challenge. Using spinning disk confocal
      microscopy, we observed the very early effector events of the immune response.
      Simultaneous, real-time visualization of predominant neutrophil and extremely
      rare CD4 T cell trafficking in the challenged skin vasculature was noted (one
      rolling CD4 T cell for every 10-18 rolling and adherent neutrophils). We
      demonstrate that neutrophil adhesion during the early CS response was reduced in
      C5a receptor-deficient (C5aR-/-) mice or leukotriene B4 receptor antagonist
      treated mice, whereas CD4 T cell recruitment was only inhibited in C5aR-/- mice.
      In line with these observations, leukocyte infiltration and the associated tissue
      damage were significantly reduced in C5aR-/- mice but not in leukotriene B4
      receptor antagonist-treated wild-type mice 24 h after challenge. C5a receptor
      expression on T cells and not on tissue resident cells was important for the
      development of a CS response. Thus, by using spinning disk confocal microscopy we
      visualized the early events of an adaptive immune response and identified the
      rare but essential recruitment of CD4 T cells via the complement pathway.

PMID- 18097054
TI  - IL-13 receptor alpha2 selectively inhibits IL-13-induced responses in the murine
      lung.
AB  - IL-13 is a critical cytokine at sites of Th2 inflammation. In these locations it
      mediates its effects via a receptor complex, which contains IL-4Ralpha and IL
      13Ralpha1. A third, high-affinity IL-13 receptor, IL-13Ralpha2, also exists.
      Although it was initially felt to be a decoy receptor, this has not been formally
      demonstrated and the role(s) of this receptor has recently become controversial.
      To define the role(s) of IL-13Ralpha2 in IL-13-induced pulmonary inflammation and
      remodeling, we compared the effects of lung-targeted transgenic IL-13 in mice
      with wild-type and null IL-13Ralpha2 loci. We also investigated the effect of IL
      13Ralpha2 deficiency on the OVA-induced inflammatory response. In this study, we
      show that in the absence of IL-13Ralpha2, IL-13-induced pulmonary inflammation,
      mucus metaplasia, subepithelial fibrosis, and airway remodeling are significantly
      augmented. These changes were accompanied by increased expression and production
      of chemokines, proteases, mucin genes, and TGF-beta1. Similarly, an enhanced
      inflammatory response was observed in an OVA-induced phenotype. In contrast,
      disruption of IL-13Ralpha2 had no effect on the tissue effects of lung-targeted
      transgenic IL-4. Thus, IL-13Ralpha2 is a selective and powerful inhibitor of IL
      13-induced inflammatory, remodeling, and physiologic responses in the murine
      lung.

PMID- 18097055
TI  - Extracellular HIV-Tat induces cyclooxygenase-2 in glial cells through activation
      of nuclear factor of activated T cells.
AB  - Both the HIV-1 protein Tat and cyclooxygenase-2 (COX-2) have been involved in the
      neuropathogenesis associated with HIV-1 infection. However, the relationship
      among them has not been addressed. Here, we found that extracellular Tat was able
      to induce COX-2 mRNA and protein expression and PGE2 synthesis in astrocytoma
      cell lines and primary human astrocytes. Moreover, Tat induced COX-2 promoter
      transcription. Deletion of NF-kappaB sites of the promoter did not diminish Tat
      dependent transcription. Interestingly, Tat did not induce NF-kappaB activity,
      suggesting that NF-kappaB was not necessary to control COX-2 transcription
      induced by Tat. In contrast, deletion or mutation of the NFAT and/or AP-1 site
      abrogated COX-2 induction by Tat. Moreover, Tat induced transcription of NFAT-
      and AP-1-dependent reporter genes. Transfection of a dominant negative c-Jun
      mutant protein, TAM-67, or of a dominant negative version of NFAT, efficiently
      blocked the induction of COX-2 promoter by Tat, confirming the requirement of
      both transcription factors. Moreover, Tat induced NFAT translocation to the
      nucleus and binding to the distal site of the COX-2 promoter. The importance of
      NFAT and AP-1 in COX-2 induction and PGE2 synthesis by Tat was corroborated by
      using pharmacological inhibitors of the NFAlphaTau, ERK, and JNK pathways. In
      summary, our results indicate that HIV-1 Tat was able to induce COX-2 and PGE2
      synthesis in astrocytic cells through an NFAT/AP-1-dependent mechanism.

PMID- 18097056
TI  - Cyclooxygenase-2/prostaglandin D2/CRTH2 pathway mediates double-stranded RNA
      induced enhancement of allergic airway inflammation.
AB  - Respiratory RNA viruses responsible for the common cold often worsen airway
      inflammation and bronchial responsiveness, two characteristic features of human
      asthma. We studied the effects of dsRNA, a nucleotide synthesized during viral
      replication, on airway inflammation and bronchial hyperresponsiveness in murine
      models of asthma. Intratracheal instillation of poly I:C, a synthetic dsRNA,
      increased the airway eosinophilia and enhanced bronchial hyperresponsiveness to
      methacholine in OVA-sensitized, exposed rats. These changes were associated with
      induction of cyclooxygenase-2 (COX-2) expression and COX-2-dependent PGD2
      synthesis in the lungs, particularly in alveolar macrophages. The direct
      intratracheal instillation of PGD2 enhanced the eosinophilic inflammation in OVA
      exposed animals, whereas pretreatment with a dual antagonist against the PGD2
      receptor-(CRTH2) and the thromboxane A2 receptor, but not with a thromboxane A2
      receptor-specific antagonist, nearly completely eliminated the dsRNA-induced
      worsening of airway inflammation and bronchial hyperresponsiveness. CRTH2
      deficient mice had the same degree of allergen-induced airway eosinophilia as
      wild-type mice, but they did not exhibit a dsRNA-induced increase in eosinophil
      accumulation. Our data demonstrate that COX-2-dependent production of PGD2
      followed by eosinophil recruitment into the airways via a CRTH2 receptor are the
      major pathogenetic factors responsible for the dsRNA-induced enhancement of
      airway inflammation and responsiveness.

PMID- 18097057
TI  - Activation of Rho kinase by TNF-alpha is required for JNK activation in human
      pulmonary microvascular endothelial cells.
AB  - TNF-alpha induces complex signaling events in endothelial cells (ECs), leading to
      inflammatory gene transcription and junctional permeability increases. This study
      examined the activation of RhoA and Rho kinase induced by TNF-alpha in primary
      human pulmonary microvascular ECs and its role in regulating EC responses to TNF
      alpha. TNF-alpha induced a time-dependent activation of RhoA and Rho kinase in
      these ECs. TNF-alpha also induced activation of JNK that peaked at 15 min and
      lasted for at least 3 h. Inhibition of Rho kinase using a specific
      pharmacological inhibitor, Y27632, prevented TNF-alpha-induced early and late JNK
      activation. Inhibition of RhoA protein expression using small-interfering RNA,
      however, did not prevent TNF-alpha-induced Rho kinase activation or JNK
      activation. Studies using MAPK kinase 4 (MKK4) small-interfering RNA showed that
      MKK4 was not required for TNF-alpha-induced early JNK activation and that Rho
      kinase modulated early JNK activation through MKK4-independent mechanisms. Rho
      kinase, however, modulated TNF-alpha-induced late JNK activation mainly through
      MKK4-dependent mechanisms. Activation of Rho kinase was required for JNK
      dependent IL-6 secretion induced by TNF-alpha. Moreover, inhibition of Rho kinase
      prevented TNF-alpha-induced cytoskeletal changes and permeability increases.
      Inhibition of JNK activation, however, did not prevent TNF-alpha-induced
      cytoskeletal changes, suggesting that Rho kinase did not modulate cytoskeletal
      changes through JNK activation. Therefore, Rho kinase plays important roles in EC
      responses to TNF-alpha by regulating permeability increases and JNK-dependent IL
      6 production during pulmonary inflammation.

PMID- 18097058
TI  - Commensal gut flora drives the expansion of proinflammatory CD4 T cells in the
      colonic lamina propria under normal and inflammatory conditions.
AB  - We tested in B6 mice whether the local expansion of CD4 T cells producing
      proinflammatory cytokines including IL-17 (Th17 cells) in the colonic lamina
      propria (cLP) depends on the commensal microflora. High numbers of CD4 Th17 cells
      were found in the lamina propria of the ileum and colon but not the duodenum,
      jejunum, mesenteric lymph nodes, spleen, or liver of specific pathogen-free (SPF)
      mice. The microflora is required for the accumulation of cytokine (IL-17, IFN
      gamma, TNF-alpha, IL-10)-producing CD4 T cells in the cLP because only low
      numbers of cytokine-producing cLP CD4 T cells were found in syngeneic (age- and
      sex-matched) germfree mice. The fraction of cLP Th17 cells was higher in (type I
      and type II) IFN- but not IL-4- or IL-12p40-deficient SPF congenics. cLP CD4 Th17
      cells produce IL-17 but not IFN-gamma, TNF-alpha, IL-4, or IL-10. cLP CD4 Th17
      cells accumulate locally in colitis induced by adoptive transfer of IFN-gamma+/+
      or IFN-gamma-/- CD4 T cells into congenic SPF (but not germfree) RAG-/- hosts. In
      this colitis model, cLP CD4 T cells that "spontaneously" produce IL-17
      progressively increase in number in the inflamed cLP, and increasing serum IL-17
      levels appear as the disease progresses. Commensal bacteria-driven, local
      expansion of cLP CD4 Th17 cells may contribute to the pathogenesis of this
      inflammatory bowel disease.

PMID- 18097059
TI  - Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and
      fibroblast accumulation and function.
AB  - Wounds heal through a highly regulated, self-limited inflammatory response,
      however, precise inflammatory mediators have not been fully delineated. In this
      study, we report that in a mouse model of excisional skin wound healing the
      chemokine CX3CL1 and its receptor CX3CR1 were both highly induced at wound sites;
      CX3CL1 colocalized with macrophages and endothelial cells, whereas CX3CR1
      colocalized mainly with macrophages and fibroblasts. Loss of CX3CR1 function
      delayed wound closure in both CX3CR1 knockout (KO) mice and in wild-type mice
      infused with anti-CX3CR1-neutralizing Ab. Conversely, transfer of bone marrow
      from donor wild-type mice, but not from donor CX3CR1 KO mice, restored wound
      healing to normal in CX3CR1 KO-recipient mice. Direct effects of CX3CR1
      disruption at the wound site included marked reduction of macrophages and
      macrophage products, such as TGF-beta1 and vascular endothelial growth factor.
      Consistent with this, we observed reduced alpha-smooth muscle actin (a marker for
      myofibroblasts) and collagen deposition in skin from wounded CX3CR1 KO mice, as
      well as reduced neovascularization. Together, the data support a molecular model
      of skin wound repair in which CX3CR1 mediates direct recruitment of bone marrow
      derived monocytes/macrophages which release profibrotic and angiogenic mediators.

PMID- 18097060
TI  - Targeting immune complex-mediated hypersensitivity with recombinant soluble human
      FcgammaRIA (CD64A).
AB  - Binding of Ag-Ab immune complexes to cellular FcgammaR promotes cell activation,
      release of inflammatory mediators, and tissue destruction characteristic of
      autoimmune disease. To evaluate whether a soluble FcgammaR could block the
      proinflammatory effects of immune complexes, recombinant human (rh) versions of
      FcgammaRIA, FcgammaRIIA, and FcgammaRIIIA were prepared. Binding of rh-FcgammaRIA
      to IgG was of high affinity (KD=1.7x10(-10) M), whereas rh-FcgammaRIIA and rh
      FcgammaRIIIA bound with low affinity (KD=0.6-1.9x10(-6) M). All rh-FcgammaR
      reduced immune complex precipitation, blocked complement-mediated lysis of Ab
      sensitized RBC, and inhibited immune complex-mediated production of IL-6, IL-13,
      MCP-1, and TNF-alpha by cultured mast cells. Local or systemic delivery only of
      rh-FcgammaRIA, however, reduced edema and neutrophil infiltration in the
      cutaneous Arthus reaction in mice. 125I-labeled rh-FcgammaRIA was cleared from
      mouse blood with a rapid distribution phase followed by a slow elimination phase
      with a t1/2gamma of approximately 130 h. The highest percentage of injected
      radioactivity accumulated in blood approximately liver approximately
      carcass>kidney. s.c. dosing of rh-FcgammaRIA resulted in lower serum levels of
      inflammatory cytokines and prevented paw swelling and joint damage in a murine
      model of collagen Ab-induced arthritis. These data demonstrate that rh-FcgammaRIA
      is an effective inhibitor of type III hypersensitivity.

PMID- 18097062
TI  - A role for macrophage migration inhibitory factor in the neonatal respiratory
      distress syndrome.
AB  - Using a mouse model of neonatal respiratory distress syndrome (RDS), we
      demonstrate a central role for macrophage migration inhibitory factor (MIF) in
      lung maturation at the developmental stage when human neonates are most
      susceptible to RDS. We prematurely delivered mouse pups at embryonic day 18,
      during the early saccular stage of pulmonary development. Only 8% of the
      prematurely delivered pups genetically deficient in MIF survived 8 h vs 75% of
      wild-type controls (p<0.001). This phenotype was corrected when pups of all
      genotypes were bred from dams heterozygote for MIF deficiency. Local production
      of MIF in the lung increased at embryonic day 18, continued until full-term at
      embryonic day 19.5, and decreased in adulthood, thus coinciding with this
      developmental window. The lungs of pups genetically deficient in MIF were less
      mature upon histological evaluation, and demonstrated lower levels of vascular
      endothelial growth factor and corticosterone--two factors that promote fetal lung
      maturation. In vitro studies support a role for MIF in surfactant production by
      pulmonary epithelial cells. In a cohort of human neonates with RDS, higher
      intrapulmonary MIF levels were associated with a lower likelihood of developing
      bronchopulmonary dysplasia, a sequelae of RDS (p<0.03). This study demonstrates
      for the first time a role for MIF in lung maturation, and supports a protective
      role for MIF in newborn lung disease.

PMID- 18097061
TI  - Integrin alphaDbeta2 is dynamically expressed by inflamed macrophages and alters
      the natural history of lethal systemic infections.
AB  - The leukocyte integrins have critical roles in host defense and inflammatory
      tissue injury. We found that integrin alphaDbeta2, a novel but largely
      uncharacterized member of this family, is restricted to subsets of macrophages
      and a small population of circulating leukocytes in wild-type mice in the absence
      of inflammatory challenge and is expressed in regulated fashion during cytokine
      induced macrophage differentiation in vitro. alphaDbeta2 is highly displayed on
      splenic red pulp macrophages and mediates their adhesion to local targets,
      identifying key functional activity. In response to challenge with Plasmodium
      berghei, a malarial pathogen that models systemic infection and inflammatory
      injury, new populations of alphaD+ macrophages evolved in the spleen and liver.
      Unexpectedly, targeted deletion of alphaD conferred a survival advantage in P.
      berghei infection over a 30-day observation period. Mechanistic studies
      demonstrated that the increased survival of alphaD-/- animals at these time
      points is not attributed to differences in magnitude of anemia or parasitemia or
      to alterations in splenic microanatomy, each of which is a key variable in the
      natural history of P. berghei infection, and indicated that an altered pattern of
      inflammatory cytokines may contribute to the difference in mortality. In contrast
      to the outcome in malarial challenge, death of alphaD-/- animals was accelerated
      in a model of Salmonella sepsis, demonstrating differential rather than
      stereotyped roles for alphaDbeta2 in systemic infection. These studies identify
      previously unrecognized and unique activities of alphaDbeta2, and macrophages
      that express it, in host defense and injury.

PMID- 18097063
TI  - Peroxisome proliferator-activated receptor-gamma ligand, 15-deoxy-Delta12,14
      prostaglandin J2, reduces neutrophil migration via a nitric oxide pathway.
AB  - Ligands for peroxisome proliferator-activated receptor gamma (PPAR-gamma), such
      as 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) have been implicated as a new
      class of anti-inflammatory compounds with possible clinical applications. Based
      on this concept, this investigation was designed to determine the effect of 15d
      PGJ2-mediated activation of PPAR-gamma ligand on neutrophil migration after an
      inflammatory stimulus and clarify the underlying molecular mechanisms using a
      mouse model of peritonitis. Our results demonstrated that 15d-PGJ2 administration
      decreases leukocyte rolling and adhesion to the inflamed mesenteric tissues by a
      mechanism dependent on NO. Specifically, pharmacological inhibitors of NO
      synthase remarkably abrogated the 15d-PGJ2-mediated suppression of neutrophil
      migration to the inflammatory site. Moreover, inducible NOS-/- mice were not
      susceptible to 15d-PGJ2-mediated suppression of neutrophil migration to the
      inflammatory sites when compared with their wild type. In addition, 15d-PGJ2
      mediated suppression of neutrophil migration appeared to be independent of the
      production of cytokines and chemokines, since their production were not
      significantly affected in the carrageenan-injected peritoneal cavities. Finally,
      up-regulation of carrageenan-triggered ICAM-1 expression in the mesenteric
      microcirculation vessels was abrogated by pretreatment of wild-type mice with 15d
      PGJ2, whereas 15d-PGJ2 inhibited F-actin rearrangement process in neutrophils.
      Taken together these findings demonstrated that 15d-PGJ2 suppresses inflammation
      initiated neutrophil migration in a mechanism dependent on NO production in
      mesenteric tissues.

PMID- 18097064
TI  - Critical but overlapping role of FcgammaRIII and FcgammaRIV in activation of
      murine neutrophils by immobilized immune complexes.
AB  - Immune complex-induced activation of neutrophils through cell surface FcRs plays
      a central role in the pathogenesis of autoimmune inflammatory diseases. These
      diseases are often modeled using genetically modified mice. However, in contrast
      to the number of studies on human cells, the identity of FcRs involved in immune
      complex activation of murine neutrophils is at present unknown. Furthermore,
      little is known about the cellular functions mediated by the recently identified
      murine FcgammaRIV. In this study, we tested the identity of FcRs involved in the
      activation of neutrophils by plate-bound immune complexes, using various knockout
      mouse strains, function-blocking mAbs, or the combination of both approaches.
      Activation of murine neutrophils by immobilized IgG immune complexes was
      abrogated in FcR gamma-chain-deficient cells, but not by the single or combined
      deficiency of the gamma-chain-associated FcgammaRI and FcgammaRIII, or by
      blocking Abs against either FcgammaRIII or FcgammaRIV alone. However, treatment
      of FcgammaRIII-deficient neutrophils with FcgammaRIV-blocking Abs or simultaneous
      blocking of FcgammaRIII and FcgammaRIV in wild-type cells completely inhibited
      the immune complex-induced cellular responses. In parallel studies, activation of
      human neutrophils by immobilized immune complexes was abrogated by blocking Abs
      against either FcgammaRIIA or FcgammaRIIIB alone. Taken together, neutrophil
      activation by immobilized immune complexes requires the murine
      FcgammaRIII/FcgammaRIV or the human FcgammaRIIA/FcgammaRIIIB molecules. Although
      both of the two human receptors are required for this response, the two murine
      receptors play overlapping, redundant roles. These results promote our
      understanding of autoimmune diseases and identify an IgG-dependent cellular
      function of FcgammaRIV.

PMID- 18097065
TI  - Selective estrogen receptor-beta agonists repress transcription of
      proinflammatory genes.
AB  - In addition to their role in the development and function of the reproductive
      system, estrogens have significant anti-inflammatory properties. Although both
      estrogen receptors (ERs) can mediate anti-inflammatory actions, ERbeta is a more
      desirable therapeutic target because ERalpha mediates the proliferative effects
      of estrogens on the mammary gland and uterus. In fact, selective ERbeta agonists
      have beneficial effects in preclinical models involving inflammation without
      causing growth-promoting effects on the uterus or mammary gland. However, their
      mechanism of action is unclear. The purpose of this study was to use microarray
      analysis to determine whether ERbeta-selective compounds produce their anti
      inflammatory effects by repressing transcription of proinflammatory genes. We
      identified 49 genes that were activated by TNF-alpha in human osteosarcoma U2OS
      cells expressing ERbeta. Estradiol treatment significantly reduced the activation
      by TNF-alpha on 18 genes via ERbeta or ERalpha. Most repressed genes were
      inflammatory genes, such as TNF-alpha, IL-6, and CSF2. Three ERbeta-selective
      compounds, ERB-041, WAY-202196, and WAY-214156, repressed the expression of these
      and other inflammatory genes. ERB-041 was the most ERbeta-selective compound,
      whereas WAY-202196 and WAY-214156 were the most potent. The ERbeta-selective
      compounds repressed inflammatory genes by recruiting the coactivator, SRC-2. ERB
      041 also repressed cytokine genes in PBMCs, demonstrating that ERbeta-selective
      estrogens have anti-inflammatory properties in immune cells. Our study suggests
      that the anti-inflammatory effects of ERB-041 and other ERbeta-selective
      estrogens in animal models are due to transcriptional repression of
      proinflammatory genes. These compounds might represent a new class of drugs to
      treat inflammatory disorders.

PMID- 18097067
TI  - Recurrent staphylococcal cellulitis and subcutaneous abscesses in a child with
      autoantibodies against IL-6.
AB  - We investigated an otherwise healthy patient presenting two episodes of
      staphylococcal cellulitis and abscesses, accompanied by high fever and biological
      signs of inflammation but, paradoxically, with no detectable increase in serum
      levels of C-reactive protein (CRP), an IL-6-responsive protein synthesized in the
      liver. Following in vitro activation of whole blood cells from the patient with
      multiple cytokines, TLR agonists, heat-killed bacteria, and mitogens, we observed
      a profound and specific impairment of IL-6 secretion. However, the patient's
      PBMCs, activated in the same conditions but in the absence of the patient's
      plasma, secreted IL-6 normally. The patient's serum contained high titers of IgG1
      autoantibodies against IL-6, which specifically neutralized IL-6 production by
      control PBMCs as well as IL-6 responses in the human hepatocellular carcinoma
      cell line Hep3B. These anti-IL-6 autoantibodies were detected over a period of 4
      years, in the absence of any other autoantibodies. Our results indicate that
      these Abs probably prevented an increase in CRP concentration during infection
      and that impaired IL-6-mediated immunity may have contributed to staphylococcal
      disease. Patients with severe bacterial infections and low serum CRP
      concentrations should be tested for anti-IL-6 autoantibodies, especially in the
      presence of other clinical and biological signs of inflammation.

PMID- 18097066
TI  - Prostaglandin E2 mediates IL-1beta-related fibroblast mitogenic effects in acute
      lung injury through differential utilization of prostanoid receptors.
AB  - The fibroproliferative response to acute lung injury (ALI) results in severe,
      persistent respiratory dysfunction. We have reported that IL-1beta is elevated in
      pulmonary edema fluid in those with ALI and mediates an autocrine-acting,
      fibroblast mitogenic pathway. In this study, we examine the role of IL-1beta
      mediated induction of cyclooxygenase-2 and PGE2, and evaluate the significance of
      individual E prostanoid (EP) receptors in mediating the fibroproliferative
      effects of IL-1beta in ALI. Blocking studies on human lung fibroblasts indicate
      that IL-1beta is the major cyclooxygenase-2 mRNA and PGE2-inducing factor in
      pulmonary edema fluid and accounts for the differential PGE2 induction noted in
      samples from ALI patients. Surprisingly, we found that PGE2 produced by IL-1beta
      stimulated fibroblasts enhances fibroblast proliferation. Further studies
      revealed that the effect of fibroblast proliferation is biphasic, with the
      promitogenic effect of PGE2 noted at concentrations close to that detected in
      pulmonary edema fluid from ALI patients. The suppressive effects of PGE2 were
      mimicked by the EP2-selective receptor agonist, butaprost, by cAMP activation,
      and were lost in murine lung fibroblasts that lack EP2. Conversely, the
      promitogenic effects of mid-range concentrations of PGE2 were mimicked by the EP3
      selective agent, sulprostone, by cAMP reduction, and lost upon inhibition of Gi
      mediated signaling with pertussis toxin. Taken together, these data demonstrate
      that PGE2 can stimulate or inhibit fibroblast proliferation at clinically
      relevant concentrations, via preferential signaling through EP3 or EP2 receptors,
      respectively. Such mechanisms may drive the fibroproliferative response to ALI.

PMID- 18097068
TI  - IL-17RA and IL-17RC receptors are essential for IL-17A-induced ELR+ CXC chemokine
      expression in synoviocytes and are overexpressed in rheumatoid blood.
AB  - IL-17A is a cytokine secreted by the newly described Th17 cells implicated in
      rheumatoid arthritis (RA). Less is known about its receptors in synoviocytes. IL
      17RA and IL-17RC were found to be overexpressed in RA peripheral whole blood and
      their expression was detected locally in RA synovium. In vitro, IL-17A synergized
      with TNF-alpha to induce IL-6, IL-8, CCL-20, and matrix metalloproteinase-3.
      Using microarrays, a specific up-regulation of Glu-Leu-Arg+ CXC chemokines was
      observed in IL-17A-treated synoviocytes. Using both posttranslational inhibitions
      by silencing interfering RNA and extracellular blockade by specific inhibitors,
      we showed that both IL-17RA and IL-17RC are implicated in IL-17A-induced IL-6
      secretion, whereas in the presence of TNF-alpha, the inhibition of both receptors
      was needed to down-regulate IL-17A-induced IL-6 and CCL-20 secretion. Thus, IL
      17A-induced IL-6, IL-8, and CCL20 secretion was dependent on both IL-17RA and IL
      17RC, which are overexpressed in RA patients. IL-17A-induced pathogenic effects
      may be modulated by IL-17RA and/or IL-17RC antagonism.

PMID- 18097069
TI  - Is the performance of cancer services influenced more by hospital factors or by
      specialization?
AB  - The Cancer Plan for England, introduced in 2000, has promoted cancer service
      specialization. We have investigated how far specialization and general hospital
      factors each contributed to service performance for four common cancers-breast,
      colorectal, lung and prostate-at the time of the Cancer Plan. Performance
      measures of service standards, waiting time to treatment, satisfaction with care,
      in-hospital mortality and population-level survival were identified from
      secondary data sets for 167 acute hospitals and 34 cancer networks in England. We
      correlated rankings of networks and hospitals between the data sets using non
      parametric statistics. At cancer network level, peer-review service standards
      were associated (P < 0.05) with 1-year survival for colorectal and lung cancers,
      and waiting times for lung cancer. At hospital level, standards were associated
      (P < 0.01) with waiting time to treatment for breast and colorectal cancers.
      However, there were stronger associations between specializations within
      hospitals: rankings of breast, colorectal and prostate cancers were highly
      associated (P < 0.001) for 5-year survival, patient satisfaction, standards and
      in-hospital mortality. Hospital-level differences appear to contribute more to
      variations in cancer performance than specialization differences within
      hospitals. The findings may be used for planning and commissioning better cancer
      services.

PMID- 18097070
TI  - Twelve-month-old girl with myocardial ischaemia.

PMID- 18097071
TI  - Quantitative estimation of thermal contact conductance of a real front-end
      component at SPring-8 front-ends.
AB  - The thermal contact conductance (TCC) of a real front-end component at SPring-8
      has been quantitatively estimated by comparing the results of experiments with
      those of finite-element analyses. In this paper one of the methods of predicting
      the TCC of a real instrument is presented. A metal filter assembly, which is an
      indirect-cooling instrument, was selected for the estimation of the TCC. The
      temperature of the metal filter assembly for the maximum heat load of synchrotron
      radiation was calculated from the TCC that is expected under normal conditions.
      This study contributes towards the ongoing research program being conducted to
      investigate the real thermal limitation of all front-end high-heat-load
      components.

PMID- 18097072
TI  - Internally cooled V-shape inclined monochromator.
AB  - A simple variant of a Si internally cooled inclined X-ray monochromator of
      reasonable size is proposed. It has two inclined surfaces oriented into a V
      shape. This design substantially decreases the surface deformations introduced by
      radiation heat, and the size of the crystal is still feasible for a 50 mm broad
      impinging bending magnet or wiggler beam. The possibility of sagittal focusing of
      the diffracted beam is also discussed.

PMID- 18097073
TI  - Design and performance of an ultra-high-vacuum-compatible artificial channel-cut
      monochromator.
AB  - The design and performance of a novel ultra-high-vacuum-compatible artificial
      channel-cut monochromator that has been commissioned at undulator beamline 8-ID-I
      at the Advanced Photon Source are presented. Details of the mechanical and
      optical design, control system implementation and performance of the new device
      are given. The monochromator was designed to meet the challenging stability and
      optical requirements of the X-ray photon correlation spectroscopy program hosted
      at this beamline. In particular, the device incorporates a novel in-vacuum sine
      bar drive mechanism for the combined pitch motion of the two crystals and a
      flexure-based high-stiffness weak-link mechanism for fine-tuning the pitch and
      roll of the second crystal relative to the first crystal. The monochromator
      delivers an exceptionally uniform and stable beam and thereby improved brilliance
      preservation.

PMID- 18097074
TI  - Time-space transformation of femtosecond free-electron laser pulses by periodical
      multilayers.
AB  - A scattering scheme to probe the time evolution of femtosecond pulses of a soft X
      ray free-electron laser (FEL) in a multilayer structure is presented. The
      response of periodic multilayers (MLs) with low and high absorption and various
      numbers of bi-layers to a pulse train of Gaussian-shaped sub-pulses is
      calculated. During the passage of the incident pulse the interaction length
      increases and the scattering profile changes as a function of the spatial
      position of the pulse within the sample. Owing to stretching of the reflected
      pulse compared with the incident pulse, the time-dependent scattering evolution
      in the ML can be visualized along a spatial coordinate of a position-sensitive
      detector. Using a scattering geometry where the mean energy of the incident pulse
      train is slightly detuned from the energy of maximum reflectivity at the first
      order peak, the response of the ML shows an oscillator behaviour along this
      spatial coordinate at the detector. For a FEL wavelength of 6.4 nm this effect is
      promising for MLs with low absorption, such as La/C for example. On the other
      hand, the oscillations will not be present for MLs with high absorption.
      Therefore a low-absorbing ML is a sensitive tool for studying the possible change
      of sample absorption caused by femtosecond-pulse interaction with matter.

PMID- 18097075
TI  - X-ray spectromicroscopy with the scanning transmission X-ray microscope at BESSY
      II.
AB  - Using the scanning transmission X-ray microscope at BESSY II, colloidal
      structures from a Chernozem soil have been studied with a spatial resolution
      around 60 nm and a spectral resolution of 1,700 at the K-absorption edge of
      carbon. Elemental mapping has been used to determine the distribution of organic
      matter within the colloidal structures. Spectra have been extracted from image
      stacks to obtain information about the chemical state. For the analysis of the
      latter, principal component analysis and cluster analysis have been applied. It
      was possible, for example, to discriminate clay particles against organic
      components.

PMID- 18097076
TI  - Morphological study of early-stage lung cancer using synchrotron radiation.
AB  - In the present study the feasibility of applying synchrotron radiation to the
      morphological study of early-stage lung cancer has been investigated. Lewis lung
      cancer was implanted and grown in a nude mouse for different periods, and imaged
      using phase-contrast synchrotron X-rays. Morphological differences were clearly
      shown between the normal lung and cancerous tissues at this early stage.
      Irregular and tortuous angiogenesis were found in the periphery region of the
      developing lung cancer. Results from this study indicate that synchrotron X-rays
      can be used for imaging cancer development and progression with minimal invasion.

PMID- 18097077
TI  - High-performance X-ray detectors for the new powder diffraction beamline I11 at
      Diamond.
AB  - The design and performance characterization of a new light-weight and compact X
      ray scintillation detector is presented. The detectors are intended for use on
      the new I11 powder diffraction beamline at the third-generation Diamond
      synchrotron facility where X-ray beams of high photon brightness are generated by
      insertion devices. The performance characteristics of these detection units were
      measured first using a radioactive source (efficiency of detection and background
      count rate) and then synchrotron X-rays (peak stability, light yield linearity
      and response consistency). Here, the results obtained from these tests are
      reported, and the suitability of the design for the Diamond powder beamline is
      demonstrated by presenting diffraction data obtained from a silicon powder
      standard using a prototype multicrystal analyser stage.

PMID- 18097078
TI  - Cost-effective upgrade of a focusing system for inelastic X-ray scattering
      experiments under high pressure.
AB  - Inelastic X-ray scattering (IXS) is a powerful technique capable of probing the
      dynamic behavior and electronic structure of materials. For IXS experiments under
      high pressure up to the megabar range using state-of-the-art diamond-anvil-cell
      technology, the sample volume is limited to the order of 1 x 10(-3) mm(3) for
      which a beam focus of the same order and less is often required. In this paper a
      scheme utilizing a set of low-cost and compact Kirkpatrick-Baez mirrors for
      upgrading the existing optical system of the Taiwan IXS beamline at SPring-8 is
      described. The scheme as implemented improves the focus to 13 microm x 16 microm
      (horizontal x vertical) with a transmission of up to 72% and a flux density gain
      of over 30 times, which has enhanced substantially the efficiency of the beamline
      for high-pressure research.

PMID- 18097079
TI  - Relics in medieval altarpieces? Combining X-ray tomographic, laminographic and
      phase-contrast imaging to visualize thin organic objects in paintings.
AB  - X-ray radiography is a common tool in the study of old master paintings.
      Transmission imaging can visualize hidden paint layers as well as the structure
      of the panel or canvas. In some medieval altarpieces, relics seem to have been
      imbedded in the wooden carrier of paintings. These are most probably thin organic
      fibrous materials such as paper or textile, which in traditional radiography are
      shadowed by the more absorbing surrounding material. This paper studies the
      application potential of synchrotron-based tomographic and laminographic imaging
      complemented with phase-contrast imaging for detection of such relics. The
      techniques are applied to a dummy painting. The results demonstrate that by using
      these imaging methods it is possible to three-dimensionally visualize hidden
      cavities in panels and detect thin fibrous low-Z materials sandwiched between a
      high-Z paint layer and a thick wooden panel.

PMID- 18097080
TI  - Dose, exposure time and resolution in serial X-ray crystallography.
AB  - The resolution of X-ray diffraction microscopy is limited by the maximum dose
      that can be delivered prior to sample damage. In the proposed serial
      crystallography method, the damage problem is addressed by distributing the total
      dose over many identical hydrated macromolecules running continuously in a single
      file train across a continuous X-ray beam, and resolution is then limited only by
      the available molecular and X-ray fluxes and molecular alignment. Orientation of
      the diffracting molecules is achieved by laser alignment. The incident X-ray
      fluence (energy/area) is evaluated that is required to obtain a given resolution
      from (i) an analytical model, giving the count rate at the maximum scattering
      angle for a model protein, (ii) explicit simulation of diffraction patterns for a
      GroEL-GroES protein complex, and (iii) the spatial frequency cut-off of the
      transfer function following iterative solution of the phase problem, and
      reconstruction of an electron density map in the projection approximation. These
      calculations include counting shot noise and multiple starts of the phasing
      algorithm. The results indicate counting time and the number of proteins needed
      within the beam at any instant for a given resolution and X-ray flux. An inverse
      fourth-power dependence of exposure time on resolution is confirmed, with
      important implications for all coherent X-ray imaging. It is found that multiple
      single-file protein beams will be needed for sub-nanometer resolution on current
      third-generation synchrotrons, but not on fourth-generation designs, where
      reconstruction of secondary protein structure at a resolution of 7 A should be
      possible with relatively short exposures.

PMID- 18097081
TI  - Radiobiological features of the anti-cancer strategies involving synchrotron X
      rays.
AB  - Synchrotrons are opening new paths in innovative anti-cancer radiotherapy
      strategies. Indeed, the fluence of X-rays induced by synchrotrons is so high
      (10(6) times higher than standard medical irradiators) that it enables the
      production of X-ray beams tunable in energy (monochromatic beams) and in size
      (micrometric beams). Monochromatic synchrotron X-ray beams theoretically permit
      photoactivate high-Z elements to be introduced in or close to tumours in order to
      increase the yield of damage by enhanced energy photoabsorption. This is notably
      the case of attempts with iodinated contrast agents used in tumour imaging (the
      computed tomography therapy approach) and with platinated agents used in
      chemotherapy (the PAT-Plat approach). Micrometric synchrotron X-ray beams
      theoretically permit very high radiation doses to accumulate in tumours by using
      arrays of parallel microplanar beams that spare the surrounding tissues (the
      microbeam radiation therapy approach). These anti-cancer applications of
      synchrotron radiation have been developed at the European Synchrotron Radiation
      Facility to be applied to glioma, one of the tumour tissues most refractory to
      standard treatments. In the present paper the molecular and cellular mechanisms
      involved in these three approaches are reviewed, in the context of recent
      advances in radiobiology. Furthermore, by considering the unavoidable biases, an
      attempt to propose a comparison of the different results obtained in preclinical
      trials dealing with rats bearing tumours is given.

PMID- 18097082
TI  - Microstrain in hydroxyapatite carbon nanotube composites.
AB  - Synchrotron radiation diffraction data were collected from hydroxyapatite-carbon
      nanotube bioceramic composites to determine the crystallite size and to measure
      changes in non-uniform strain. Estimates of crystallite size and strain were
      determined by line-profile fitting of discrete peaks and these were compared with
      a Rietveld whole-pattern analysis. Overall the two analysis methods produced very
      similar numbers. In the commercial hydroxyapatite material, one reflection in
      particular, (0 2 3), has higher crystallite size and lower strain values in
      comparison with laboratory-synthesized material. This could indicate preferential
      crystal growth in the [0 2 3] direction in the commercial material. From the
      measured strains in the pure material and the composite, there was a degree of
      bonding between the matrix and strengthening fibres. However, increasing the
      amount of carbon nanotubes in the composite has increased the strain in the
      material, which is undesirable for biomedical implant applications.

PMID- 18097083
TI  - Bond cutting in Cs-doped tris(8-hydroxyquinoline) aluminium.
AB  - A series of Cs 4d and Al 2p spectra associated with valence-band and cut-off
      spectra have been used to characterize the interaction between caesium and tris(8
      hydroxyquinoline) aluminium (Alq(3)) molecules in a Cs-doped Alq(3) layer. The Cs
      4d and Al 2p spectra were tuned to be very surface sensitive by selecting a
      photon energy of 120 eV at the National Synchrotron Radiation Research Center,
      Taiwan. A critical Cs concentration exists, above which a new Al 2p signal
      appears next to the Al 2p peak of Alq(3) in the lower binding-energy side. The Al
      2p signal was analyzed and assigned as being contributed from a mixture of
      Alq(2), Alq and Al. Experimental data supported the observation that bond cutting
      of Alq(3) by the doped Cs atoms occurred at high Cs doping concentration.

PMID- 18097084
TI  - X-ray diffractometry and topography of lattice plane curvature in thermally
      deformed Si wafer.
AB  - The correlation between the microscopic lattice plane curvature and the
      dislocation structure in thermal warpage of 200 mm-diameter Czochralski Si (001)
      wafers has been investigated using high-resolution X-ray diffractometry and
      topography. It is found that the (004) lattice plane curvature is locally
      confined between two neighboring slip bands, with the rotation axis parallel to
      the slip bands. High-resolution topography reveals that the curvature resulted
      from a fragmented dislocation structure. The local confinement is attributed to
      the multiplication of the dislocations that are generated between the two slip
      bands.

PMID- 18097085
TI  - Quantitative studies of pyrocarbon-coated materials using synchrotron radiation.
AB  - Phase-contrast imaging provides enhanced image contrast and is important for non
      destructive evaluation of structural materials. In this paper, experimental
      results on in-line phase-contrast imaging using a synchrotron source (ELETTRA,
      Italy) for objects required in material science applications are discussed.
      Experiments have been carried out on two types of samples, pyrocarbon-coated
      zirconia and pyrocarbon-coated alumina microspheres. These have applications in
      both reactor and industrial fields. The phase-contrast imaging technique is found
      to be very useful in visualizing and determining the coating thickness of
      pyrocarbon on zirconia and alumina microspheres. The experiments were carried out
      at X-ray energies of 16, 18 and 20 keV and different object-to-detector
      distances. The results describe the contrast values and signal-to-noise ratio for
      both samples. A comprehensive study was carried out to determine the thickness of
      the pyrocarbon coating on zirconia and alumina microspheres of diameter 500
      microm. The advantages of phase-contrast images are discussed in terms of
      contrast and resolution, and a comparison is made with absorption images. The
      results show considerable improvement in contrast with phase-contrast imaging as
      compared with absorption radiography.

PMID- 18097086
TI  - Beam-shaping condenser lenses for full-field transmission X-ray microscopy.
AB  - A new type of diffractive X-ray optical elements is reported, which have been
      used as beam-shaping condenser lenses in full-field transmission X-ray
      microscopes. These devices produce a square-shaped flat-top illumination on the
      sample matched to the field of view. The size of the illumination can easily be
      designed depending on the geometry and requirements of the specific experimental
      station. Gold and silicon beam-shapers have been fabricated and tested in full
      field microscopes in the hard and soft X-ray regimes, respectively.

PMID- 18097091
TI  - Structure of HsaD, a steroid-degrading hydrolase, from Mycobacterium
      tuberculosis.
AB  - Tuberculosis is a major cause of death worldwide. Understanding of the
      pathogenicity of Mycobacterium tuberculosis has been advanced by gene analysis
      and has led to the identification of genes that are important for intracellular
      survival in macrophages. One of these genes encodes HsaD, a meta-cleavage product
      (MCP) hydrolase that catalyzes the hydrolytic cleavage of a carbon-carbon bond in
      cholesterol metabolism. This paper describes the production of HsaD as a
      recombinant protein and, following crystallization, the determination of its
      three-dimensional structure to 2.35 A resolution by X-ray crystallography at the
      Diamond Light Source in Oxfordshire, England. To the authors' knowledge, this
      study constitutes the first report of a structure determined at the new
      synchrotron facility. The volume of the active-site cleft of the HsaD enzyme is
      more than double the corresponding active-site volumes of related MCP hydrolases
      involved in the catabolism of aromatic compounds, consistent with the specificity
      of HsaD for steroids such as cholesterol. Knowledge of the structure of the
      enzyme facilitates the design of inhibitors.

PMID- 18097092
TI  - The structure of melon necrotic spot virus determined at 2.8 A resolution.
AB  - The structure of melon necrotic spot virus (MNSV) was determined at 2.8 A
      resolution. Although MNSV is classified into the genus Carmovirus of the family
      Tombusviridae, the three-dimensional structure of MNSV showed a higher degree of
      similarity to tomato bushy stunt virus (TBSV), which belongs to the genus
      Tombusvirus, than to carnation mottle virus (CMtV), turnip crinkle virus (TCV) or
      cowpea mottle virus (CPMtV) from the genus Carmovirus. Thus, the classification
      of the family Tombusviridae at the genus level conflicts with the patterns of
      similarity among coat-protein structures. MNSV is one of the viruses belonging to
      the genera Tombusvirus or Carmovirus that are naturally transmitted in the soil
      by zoospores of fungal vectors. The X-ray structure of MNSV provides us with a
      representative structure of viruses transmitted by fungi.

PMID- 18097093
TI  - Semi-automated microseeding of nanolitre crystallization experiments.
AB  - A simple semi-automated microseeding procedure for nanolitre crystallization
      experiments is described. Firstly, a microseed stock solution is made from
      microcrystals using a Teflon bead. A dilution series of this microseed stock is
      then prepared and dispensed as 100 nl droplets into 96-well crystallization
      plates, facilitating the incorporation of seeding into high-throughput
      crystallization pipelines. This basic microseeding procedure has been modified to
      include additive-screening and cross-seeding methods. Five examples in which
      these techniques have been used successfully are described.

PMID- 18097094
TI  - Crystallization and preliminary X-ray studies of SdiA from Escherichia coli.
AB  - SdiA enhances cell division by regulating the ftsQAZ operon in Escherichia coli
      as a transcription activator. In addition, SdiA is suggested to play a role in
      detecting quorum signals that emanate from other species. It is therefore a
      homologue of LuxR, a cognate quorum-sensing receptor that recognizes a quorum
      signal and activates the quorum responses. To elucidate the role of SdiA and its
      functional and structural relationship to LuxR, structural studies were performed
      on E. coli SdiA. Recombinant SdiA was overexpressed, purified and crystallized at
      287 K using the hanging-drop vapour-diffusion method. X-ray diffraction data from
      a native crystal were collected with 99.7% completeness to 2.7 A resolution with
      an R(merge) of 6.0%. The crystals belong to the hexagonal space group P6(1)22 or
      P6(5)22, with unit-cell parameters a = b = 130.47, c = 125.23 A.

PMID- 18097095
TI  - Overexpression, purification and crystallization of the tetrameric form of SorC
      sorbitol operon regulator.
AB  - The sorbitol operon regulator (SorC) regulates the metabolism of L-sorbose in
      Klebsiella pneumonia. SorC was overexpressed in Escherichia coli and purified,
      and crystals were obtained of a tetrameric form. A single crystal showed X-ray
      diffraction to 3.20 A. The crystal belongs to space group P2(1)2(1)2(1), with
      unit-cell parameters a = 91.6, b = 113.3, c = 184.1 A. Analysis of the molecular
      replacement solution indicates the presence of four SorC molecules in the
      asymmetric unit.

PMID- 18097096
TI  - Characterization and crystallization of a recombinant IgE Fab fragment in complex
      with the bovine beta-lactoglobulin allergen.
AB  - A D1 Fab fragment containing the allergen-binding variable domains of the IgE
      antibody was characterized by ESI FT-ICR mass spectrometry and crystallized with
      bovine beta-lactoglobulin (BLG) using the hanging-drop vapour-diffusion method at
      293 K. X-ray data suitable for structure determination were collected to 2.8 A
      resolution using synchrotron radiation. The crystal belonged to the orthorhombic
      space group P2(1)2(1)2(1), with unit-cell parameters a = 67.0, b = 100.6, c =
      168.1 A. The three-dimensional structure of the D1 Fab fragment-BLG complex will
      provide the first insight into IgE antibody-allergen interactions at the
      molecular level.

PMID- 18097097
TI  - Overproduction, purification, crystallization and preliminary X-ray analysis of
      the peroxiredoxin domain of a larger natural hybrid protein from Thermotoga
      maritima.
AB  - Thermotoga maritima contains a natural hybrid protein constituted of two
      moieties: a peroxiredoxin domain at the N-terminus and a nitroreductase domain at
      the C-terminus. The peroxiredoxin (Prx) domain has been overproduced and purified
      from Escherichia coli cells. The recombinant Prx domain, which is homologous to
      bacterial Prx BCP and plant Prx Q, folds properly into a stable protein that
      possesses biological activity. The recombinant protein was crystallized and
      synchrotron data were collected to 2.9 A resolution. The crystals belonged to the
      tetragonal space group I422, with unit-cell parameters a = b = 176.67, c = 141.20
      A.

PMID- 18097098
TI  - Purification, identification and preliminary crystallographic studies of Pru du
      amandin, an allergenic protein from Prunus dulcis.
AB  - Food allergies appear to be one of the foremost causes of hypersensitivity
      reactions. Nut allergies account for most food allergies and are often permanent.
      The 360 kDa hexameric protein Pru du amandin, a known allergen, was purified from
      almonds (Prunus dulcis) by ammonium sulfate fractionation and ion-exchange
      chromatography. The protein was identified by a BLAST homology search against the
      nonredundant sequence database. Pru du amandin belongs to the 11S legumin family
      of seed storage proteins characterized by the presence of a cupin motif. Crystals
      were obtained by the hanging-drop vapour-diffusion method. The crystals belong to
      space group P4(1) (or P4(3)), with unit-cell parameters a = b = 150.7, c = 164.9
      A.

PMID- 18097099
TI  - Overproduction, crystallization and preliminary X-ray analysis of the putative L
      ascorbate-6-phosphate lactonase UlaG from Escherichia coli.
AB  - UlaG, the putative L-ascorbate-6-phosphate lactonase encoded by the ulaG gene
      from the utilization of L-ascorbate regulon in Escherichia coli, has been cloned,
      overexpressed, purified using standard chromatographic techniques and
      crystallized. Crystals were obtained by sitting-drop vapour diffusion at 293 K.
      Preliminary X-ray diffraction analysis revealed that the UlaG crystals belonged
      to the monoclinic space group C2, with unit-cell parameters a = 104.52, b =
      180.69, c = 112.88 A, beta = 103.26 degrees. The asymmetric unit is expected to
      contain six copies of UlaG, with a corresponding volume per protein weight of
      2.16 A3 Da(-1) and a solvent content of 43%.

PMID- 18097100
TI  - Crystallization and preliminary crystallographic analysis of the catalytic domain
      of human flap endonuclease 1 in complex with a nicked DNA product: use of a DPCS
      kit for efficient protein-DNA complex crystallization.
AB  - Flap endonuclease 1 (FEN1) is a structure-specific nuclease that removes the
      RNA/DNA primer associated with Okazaki fragments in DNA replication. Here,
      crystals of the complex between the catalytic domain of human FEN1 and a DNA
      product have been obtained. For efficient crystallization screening, a DNA
      protein complex crystallization screening (DPCS) kit was designed based on
      commercial crystallization kits. The crystal was found to belong to space group
      P2(1), with unit-cell parameters a = 61.0, b = 101.3, c = 106.4 A, beta = 106.4
      degrees. The asymmetric unit is predicted to contain two complexes in the
      crystallographic asymmetric unit. A diffraction data set was collected to a
      resolution of 2.75 A.

PMID- 18097101
TI  - Expression, crystallization and preliminary X-ray diffraction analysis of human
      paired Ig-like type 2 receptor alpha (PILRalpha).
AB  - Human paired immunoglobulin-like (Ig-like) type 2 receptor alpha (PILRalpha) is a
      type I membrane protein that is mainly expressed in immune-related cells such as
      monocytes, granulocytes and dendritic cells. PILRalpha can suppress the functions
      of such immune cells because it has the immunoreceptor tyrosine-based inhibitory
      motif (ITIM) in the intracellular region, which recruits the phosphatase Src
      homology-2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP-2) to
      inhibit phosphorylations induced by activation signals. The extracellular region
      of human PILRalpha comprises one immunoglobulin superfamily V-set domain and a
      stalk region. The V-set domain (residues 13-131) of human PILRalpha was
      overexpressed in Escherichia coli as inclusion bodies, refolded by rapid dilution
      and purified. The PILRalpha protein was successfully crystallized at 293 K using
      the sitting-drop vapour-diffusion method. The crystals diffracted to 1.3 A
      resolution at SPring-8 BL41XU; they belong to space group P2(1)2(1)2(1), with
      unit-cell parameters a = 40.4, b = 45.0, c = 56.9 A, and contain one molecule per
      asymmetric unit.

PMID- 18097102
TI  - Preliminary X-ray crystallographic analysis of SMU.573, a putative sugar kinase
      from Streptococcus mutans.
AB  - SMU.573 from Streptococcus mutans is a structurally and functionally
      uncharacterized protein that was selected for structural biology studies. Native
      and SeMet-labelled proteins were expressed with an N-His tag in Escherichia coli
      BL21 (DE3) and purified by Ni2+-chelating and size-exclusion chromatography.
      Crystals of the SeMet-labelled protein were obtained by the hanging-drop vapour
      diffusion method and a 2.5 A resolution diffraction data set was collected using
      an in-house chromium radiation source. The crystals belong to space group I4,
      with unit-cell parameters a = b = 96.53, c = 56.26 A, alpha = beta = gamma = 90
      degrees.

PMID- 18097103
TI  - Crystallization and preliminary crystallographic studies of an active-site mutant
      hydantoin racemase from Sinorhizobium meliloti CECT4114.
AB  - A recombinant active-site mutant of hydantoin racemase (C76A) from Sinorhizobium
      meliloti CECT 4114 (SmeHyuA) has been crystallized in the presence and absence of
      the substrate D,L-5-isopropyl hydantoin. Crystals of the SmeHyuA mutant suitable
      for data collection and structure determination were grown using the counter
      diffusion method. X-ray data were collected to resolutions of 2.17 and 1.85 A for
      the free and bound enzymes, respectively. Both crystals belong to space group R3
      and contain two molecules of SmeHyuA per asymmetric unit. The crystals of the
      free and complexed SmeHyuA have unit-cell parameters a = b = 85.43, c = 152.37 A
      and a = b = 85.69, c = 154.38 A, crystal volumes per protein weight (V(M)) of
      1.94 and 1.98 A3 Da(-1) and solvent contents of 36.7 and 37.9%, respectively.

PMID- 18097104
TI  - Cleaved thioredoxin fusion protein enables the crystallization of poorly soluble
      ERalpha in complex with synthetic ligands.
AB  - The ligand-binding domain (LBD) of human oestrogen receptor alpha was produced in
      Escherichia coli as a cleavable thioredoxin (Trx) fusion in order to improve
      solubility. Crystallization trials with either cleaved and purified LBD or with
      the purified fusion protein both failed to produce crystals. In another attempt,
      Trx was not removed from the LBD after endoproteolytic cleavage and its presence
      promoted nucleation and subsequent crystal growth, which allowed the structure
      determination of two different LBD-ligand-coactivator peptide complexes at 2.3 A
      resolution. This technique is likely to be applicable to other low-solubility
      proteins.

PMID- 18097107
TI  - Indian festivals: ethos and health impact.

PMID- 18097105
TI  - Crystallization and preliminary X-ray analysis of Acetivibrio cellulolyticus
      cellulosomal type II cohesin module: two versions having different linker
      lengths.
AB  - The second type II cohesin module of the cellulosomal scaffoldin polypeptide ScaB
      from Acetivibrio cellulolyticus (CohB2) was cloned into two constructs: one
      containing a short (five-residue) C-terminal linker (CohB2_S) and the second
      incorporating the full native 45-residue linker (CohB2_L). Both constructs encode
      proteins that also include the full native six-residue N-terminal linker. The
      CohB2_S and CohB2_L proteins were expressed, purified and crystallized in the
      orthorhombic crystal system, but with different unit cells and symmetries: space
      group P2(1)2(1)2(1) with unit-cell parameters a = 90.36, b = 68.65, c = 111.29 A
      for CohB2_S and space group P2(1)2(1)2 with unit-cell parameters a = 68.76, b =
      159.22, c = 44.21 A for CohB2_L. The crystals diffracted to 2.0 and 2.9 A
      resolution, respectively. The asymmetric unit of CohB2_S contains three cohesin
      molecules, while that of CohB2_L contains two molecules.

PMID- 18097108
TI  - A prospective randomized comparative study of the effects of intranasal and
      transdermal 17 beta-estradiol on postmenopausal symptoms and vaginal cytology.
AB  - CONTEXT: Investigating the adverse effects of oral hormone replacement therapy
      (HRT), the clinical effectiveness of alternative combinations and route of
      administrations. AIM: To compare the effects of intranasal and transdermal 17
      beta-estradiol combined with vaginal progesterone on vasomotor symptoms and
      vaginal cytology. SETTINGS AND DESIGN: A 12-week, prospective, randomized
      comparative study was conducted between July 2005 and September 2006. MATERIALS
      AND METHODS: Eighty postmenopausal women aged between 42-57 years, who had scores
      of > or =1.7 on the menopause rating scale-I (MRS-I) items "1-6", were randomly
      assigned to receive intranasal (300 microg/day, n =40) or transdermal (50
      microg/day, n =40) 17 beta-estradiol continuously. All patients also received a
      vaginal progesterone gel twice weekly. Vasomotor symptoms were evaluated at weeks
      0, 4, 8 and 12. Vaginal maturation index (VMI) was evaluated at weeks 0 and 12 of
      the study. STATISTICAL ANALYSES: The Mann-Whitney U and the Wilcoxon tests were
      used. P < 0.05 was regarded as significant. RESULTS: Thirty-two women in the
      intranasal and 29 women in the transdermal group completed the study. The total
      score of the MRS, the sum-scores of Factor 1 "HOT FLUSHES" and Factor 2 "PSYCHE"
      significantly decreased in both groups at week 4. Factor 3 "ATROPHY" scores
      significantly decreased only in the transdermal group at week 12. The VMI showed
      no changes within and between the two groups at the end of the study. CONCLUSION:
      Intranasal and transdermal 17beta-estradiol combined with vaginal progesterone
      gel as a continuous HRT caused a similar decrease in vasomotor symptoms but did
      not have any significant effect on VMI after 12 weeks of treatment in this study
      population.

PMID- 18097109
TI  - Miliary tuberculosis in human immunodeficiency virus infected patients not on
      antiretroviral therapy: clinical profile and response to shortcourse
      chemotherapy.
AB  - BACKGROUND: An increase in tuberculosis (TB) incidence has been associated with
      human immunodeficiency virus (HIV). AIMS: To describe the clinical
      characteristics and treatment outcome of patients with HIV and miliary TB treated
      with short-course intermittent chemotherapy in the absence of access to highly
      active antiretroviral therapy (HAART). SETTINGS AND DESIGN: Prospective study of
      HIV infected adults referred to a TB clinic between July 1999 and July 2004.
      MATERIALS AND METHODS: On diagnosis of miliary TB, patients were treated with a
      standard regimen of two months of isoniazid, rifampicin, ethambutol and
      pyrazinamide followed by four months of isoniazid and rifampicin (2EHRZ 3 /4RH 3
      ) thrice weekly and followed up for 24 months. Patients were reviewed clinically
      every month and two sputa were collected. Chest radiographs and blood
      investigations were done at two months, end of treatment and every six months
      thereafter. RESULTS: Of 498 patients with HIV and tuberculosis, 31 (6%) were
      diagnosed as miliary tuberculosis. At diagnosis, sputum smear was positive for
      acid-fast bacilli (AFB) in 14 patients (45%) and Mycobacterium tuberculosis was
      isolated in 21 (68%). The mean CD4 cell count was 129 +/- 125 cells/mm3 . Twenty
      five patients were declared cured at the end of treatment (81%) while one (3%)
      died and five (16%) failed. The recurrence rate was 19.4/100 person-years and the
      median survival was 17 months (95% CI 14 to 20). None of the patients received
      antiretroviral therapy. CONCLUSIONS: Miliary TB tends to occur among HIV infected
      patients with severe immunosuppression. Though the initial response to short
      course chemotherapy was encouraging, a high recurrence rate and mortality was
      observed indicating poor prognosis in HIV.

PMID- 18097110
TI  - Retrospective study of severe cases of leptospirosis admitted in the intensive
      care unit.
AB  - OBJECTIVES: Evaluate patient demographics, risk factors, complications,
      seropositivity, treatment and outcome among leptospirosis patients. DESIGN:
      Retrospective analysis of 104 patients admitted in the intensive care unit (ICU)
      with a clinical suspicion of leptopirosis. SETTING: Ten-bedded medical ICU in a
      medical school situated in a rural area endemic for leptospirosis. MAIN OUTCOME
      MEASURES: Seropositivity for leptospirosis, patient demographics, risk factors,
      complications, treatment and survival. RESULTS: One hundred and four patients
      were admitted with a clinical suspicion of leptospirosis. Fifty-three (50.7%)
      were serologically confirmed cases. Males dominated both groups. Most of the
      admissions were in the monsoon season. Exposure to moist soil was the main risk
      factor. The mortality in the seronegative group was 26.8% while it was only 3.8%
      in the seropositive group. Multi-organ dysfunction syndrome, primarily acute
      respiratory distress syndrome with thromboctyopenia and renal failure were the
      causes for mortality. All the patients who died presented late into the illness.
      CONCLUSIONS: The initial diagnosis of leptospirosis depends on a high index of
      clinical suspicion, routinely available diagnostic tests being unreliable in the
      initial period. A reliable, unsophisticated test should be developed for early
      detection of this disease. As leptospirosis in its early stage mimics other
      tropical infections, both medical professionals and the general public
      (especially with risk of occupational exposure) should be educated about the
      disease and the need to seek early medical intervention.

PMID- 18097111
TI  - Field rats form a major infection source of leptospirosis in and around Madurai,
      India.
AB  - AIMS: To determine the seroprevalence of leptospires and to isolate Leptospira
      spp. from field rats and bandicoots in and around Madurai. MATERIALS AND METHODS:
      Thirteen rats and five bandicoots were trapped alive from fields in and around
      Madurai. Blood samples were tested for anti-leptospiral antibodies by microscopic
      agglutination test while the urine and kidney samples were used for isolation of
      leptospires. The isolated leptospires were tested for pathogenic status (13
      degrees C test and PCR) followed by serological and genetic characterization.
      RESULTS: Serology revealed the presence of anti-leptospiral antibodies in 58%
      (7/12) of field rats and leptospires were isolated from two urine and six kidney
      samples. The bandicoots were negative in both serology and culture. Analysis of
      the isolates from field rats revealed that all the isolates were pathogenic
      except for one, which was further confirmed by serological and genetic
      characterization. Six of the seven pathogenic isolates were identified as L.
      interrogans serogroup Autumnalis serovar Akiyami A and one as L. borgpetersenii
      serogroup Javanica serovar Veldrat Batavia 46. CONCLUSIONS: Serology and
      isolation reveals that field rats are major natural carriers and shedders of
      leptospires in and around Madurai.

PMID- 18097112
TI  - Regional brain metabolism in schizophrenia: The influence of antipsychotics.
AB  - BACKGROUND: Schizophrenia has been associated with a plethora of metabolic
      changes in the brain that vary with duration and type of psychoses. Additionally,
      it has been observed that antipsychotics can further alter cerebral glucose
      metabolism. These changes resulting from antipsychotics have been postulated to
      be reflective of the duration and mechanism of action of the medication. AIMS: We
      aimed to examine the influence of antipsychotics on brain metabolism in
      individuals with schizophrenia in a naturalistic setting. SETTINGS AND DESIGN: A
      cross-sectional study was carried out by the psychiatry department of a tertiary
      care hospital in collaboration with the Radiation Medicine Centre. MATERIALS AND
      METHODS: Eighteen male patients with schizophrenia in different phases of
      treatment underwent an 18F-deoxyglucose positron emission tomography scan in a
      resting state 12 hours after the last dose of antipsychotic. STATISTICAL
      ANALYSIS: The types and duration of treatment were then compared with the
      regional glucose uptake in 14 predetermined regions of interest. The relative
      Uptake Values were further compared using SPSS 11.0. RESULTS: An immediate
      increase followed by a decrease in cortical uptake was noted while the basal
      ganglia uptake remained high, albeit with a decreasing trend. Typical
      antipsychotics were associated with lower frontal cortical and higher basal
      ganglia and cerebellar uptake as compared to atypical antipsychotics. CONCLUSION:
      The differential influence of the type and duration of antipsychotic on glucose
      uptake suggests a possible trend towards long-term side effects with typical
      medications that were not noted on clinical examination. This however needs to be
      confirmed with larger, controlled studies.

PMID- 18097113
TI  - Tumoral calcinosis of the foot with unusual presentation in an 11-year-old boy: a
      case report and review of literature.
AB  - Tumoral calcinosis is an uncommon disorder characterized by development of
      calcified masses within the soft tissues near the large joints such as the hip,
      elbow and shoulder and rarely occurs in the foot. We report the clinical,
      radiological and magnetic resonance imaging findings in a case of tumoral
      calcinosis of the foot observed in an 11-year-old boy which caused erosion of
      underlying bone and describe the surgical treatment and pathology results.

PMID- 18097114
TI  - Immune reconstitution inflammatory syndrome in a patient with cryptococcal
      lymphadenitis as the first presentation of acquired immunodeficiency syndrome.
AB  - Immune reconstitution inflammatory syndrome is commonly seen in acquired
      immunodeficiency syndrome (AIDS) patients having concomitant opportunistic
      infection, following initiation of highly active anti-retroviral therapy (HAART).
      We describe IRIS in a young man with unknown human immunodeficiency virus (HIV)
      status who presented with cryptococcal lymphadenitis as the first manifestation
      of AIDS. At presentation the patient had features overlapping with tuberculosis
      (TB) lymphadenitis which was ruled out by fine needle aspiration cytology. The
      patient responded to antifungal treatment but following the start of HAART,
      symptoms recurred which were managed conservatively. Though TB is common in
      India, a thorough workup including histopathology of lymph node should be done
      before the patient is started on anti-tuberculosis treatment. HIV infected
      patients having opportunistic co-infection should be closely monitored following
      initiation of HAART.

PMID- 18097115
TI  - Great auricular nerve involvement in leprosy: scope for misdiagnosis.
AB  - Three patients with neuritis of the great auricular nerve (GAN) have been
      reported. Two patients seen by physicians and an otolaryngologist had prominent
      and tender cord along the neck with facial edema and history of fainting attack
      in one, and erythema and hyperaesthesia of the ear in the other simulating
      vascular occlusion, which were confirmed to be leprosy in Type 1 reaction by the
      dermatologist. In the third, cold abscess in the nerve that had persisted after
      anti-leprosy treatment was mistaken as tuberculous cervical lymphadenitis by a
      surgeon since aspiration had revealed acid-fast bacilli. The probable reasons for
      misdiagnosis include rarity of involvement of the GAN and its proximity to main
      blood vessels, and the need for careful interpretation of laboratory results.

PMID- 18097116
TI  - Snap sound and detumescence: fracture penis.

PMID- 18097117
TI  - One gene, many phenotypes.
AB  - "Phenotype" is the visible or quantifiable effect of the expression of a gene,
      whereas the specific genetic constitution responsible for a phenotype is called
      "genotype". It was hoped that phenotype could be accurately predicted if the
      genotype could be characterized. But, the relationship between the genotype and
      phenotype is not straightforward. Similar genetic lesions can have entirely
      different phenotypes. In recent years, there has been tremendous progress in the
      understanding of the genetic basis of diseases. The extent to which it will be
      possible to relate findings at the DNA level to the clinical phenotype is
      difficult to delineate on many occasions. The elucidation of mechanisms
      underlying genotype-phenotype discrepancies is important as it will influence the
      use of DNA-based tests in the diagnosis, therapy and counseling of individuals
      affected with genetic disorders. This issue is pertinent to almost every aspect
      of medical practice and research in this post-genome era. In this article, we
      have tried to summarize those factors which are responsible for varied
      manifestations of lesion(s) in a single gene.

PMID- 18097118
TI  - Religion, spirituality, health and medicine: why should Indian physicians care?
AB  - Religion, spirituality, health and medicine have common roots in the conceptual
      framework of relationship amongst human beings, nature and God. Of late, there
      has been a surge in interest in understanding the interplay of religion,
      spirituality, health and medicine, both in popular and scientific literature. A
      number of published empirical studies suggest that religious involvement is
      associated with better outcomes in physical and mental health. Despite some
      methodological limitations, these studies do point towards a positive association
      between religious involvement and better health. When faced with disease,
      disability and death, many patients would like physicians to address their
      emotional and spiritual needs, as well. The renewed interest in the interaction
      of religion and spirituality with health and medicine has significant
      implications in the Indian context. Although religion is translated as dharma in
      major Indian languages, dharma and religion are etymologically different and
      dharma is closer to spirituality than religion as an organized institution.
      Religion and spirituality play important roles in the lives of millions of
      Indians and therefore, Indian physicians need to respectfully acknowledge
      religious issues and address the spiritual needs of their patients. Incorporating
      religion and spirituality into health and medicine may also go a long way in
      making the practice of medicine more holistic, ethical and compassionate. It may
      also offer new opportunities to learn more about Ayurveda and other traditional
      systems of medicine and have more enriched understanding and collaborative
      interaction between different systems of medicine. Indian physicians may also
      find religion and spirituality significant and fulfilling in their own lives.

PMID- 18097119
TI  - The Bayesian clinician.

PMID- 18097121
TI  - Replacing the illogic of anesthesia by the logic of aneuronia.

PMID- 18097120
TI  - Natural history of non-ischemic central retinal vein occlusion versus iatrogenic
      intervention.

PMID- 18097122
TI  - Drug rash with eosinophilia and systemic symptoms syndrome due to quinine.

PMID- 18097123
TI  - A massive myxoid liposarcoma with hyperferritinemia.

PMID- 18097124
TI  - Risedronate induced transient ocular myasthenia.

PMID- 18097125
TI  - Exposure to blood-borne viruses among healthcare workers in a tertiary care
      hospital in south India.

PMID- 18097126
TI  - Gabapentin and hypersensitivity syndrome.

PMID- 18097127
TI  - Diagnostic accuracy and specialist consultation patterns upon transient loss of
      consciousness in primary health care.

PMID- 18097128
TI  - Angiodysplasia of colon in a seven-year-old boy: a rare cause of intestinal
      bleeding.

PMID- 18097129
TI  - Consensus guidelines for the management of patients with digestive neuroendocrine
      tumors--well-differentiated jejunal-ileal tumor/carcinoma.

PMID- 18097130
TI  - Consensus guidelines for the management of patients with digestive neuroendocrine
      tumours: well-differentiated colon and rectum tumour/carcinoma.

PMID- 18097131
TI  - Consensus guidelines for the management of patients with liver metastases from
      digestive (neuro)endocrine tumors: foregut, midgut, hindgut, and unknown primary.

PMID- 18097132
TI  - A new case of human atransferrinemia with a previously undescribed mutation in
      the transferrin gene.
AB  - Hereditary atransferrinemia is a very rare disorder characterized by microcytic
      anemia and iron overload. It has been reported in only 10 patients in 8 families.
      The molecular basis of atransferrinemia has been determined in only 3 human
      cases. We now report a new patient with this rare disorder, who is the first
      known case in Turkey, the 11th patient reported in the published literature and
      only the 4th case of human atransferrinemia characterized on a molecular basis.
      DNA analysis of the serum transferrin gene in the patient revealed a previously
      undescribed mutation in exon 4, a G-->A transition at cDNA 410(Cys137Tyr). A
      number of previously known polymorphisms and a previously undescribed mutation at
      IVS10(-23)C-->T, presumably a polymorphism, were also documented.

PMID- 18097133
TI  - Estrogen and angiotensin II interactions determine cardio-renal damage in Dahl
      salt-sensitive rats with heart failure.
AB  - In women, the role of estrogen in the interrelationship between the progression
      of kidney and cardiac diseases is not fully understood. The present study
      attempted to elucidate the relationship between the process of cardiac remodeling
      and nephrosclerosis in ovariectomized Dahl salt-sensitive (DSS) rats with
      myocardial infarction (MI). METHODS: 60 DSS rats with MI produced by ligation of
      the left coronary artery were divided into 5 groups as follows: group 1: MI rats
      without ovariectomy (OVX); group 2: MI rats with OVX; group 3: MI and OVX rats
      with estradiol (E) (17beta-estradiol 15 mg/pellet/90 days subcutaneous pellet)
      supplementation; group 4: MI rats with OVX administered an angiotensin receptor
      antagonist (ARB), olmesartan, (2.5 mg/kg b.w. per day), and group 5: MI and OVX
      rats with E supplementation and administration of ARB in combination. Two weeks
      after ligation of the left coronary artery, OVX was carried out; this marked the
      start of the experiment. Body weight, systolic blood pressure (SBP), and urinary
      protein excretion were measured every 2 weeks for 12 weeks. Transthoracic
      echocardiogram was performed under anesthesia at 12 weeks. Blood samples for
      measurement of plasma renin activity, angiotensin (Ang) II, and aldosterone were
      obtained. At the end of the study, the heart and the kidney tissues were
      collected for light microscopic examination and evaluations of the expression of
      mRNA of angiotensin-converting enzyme and endothelial nitric oxide synthase
      (ecNOS). RESULTS: SBP in female DSS rats with MI and with or without OVX
      transiently increased at week 4 and then gradually decreased toward the end of
      the study. Administration of ARB reduced SBP significantly (p < 0.05) in rats
      with OVX independently of E supplementation. OVX significantly (p < 0.05)
      increased and E supplementation further increased (p < 0.01) urinary protein
      excretion. E supplementation plus ARB administration significantly decreased
      urinary protein excretion. OVX increased activity in renin-angiotensin
      aldosterone system (RAS) and both E and ARB supplementation suppressed RAS (p <
      0.05). Expression of ecNOS was decreased in the rats with OVX and this was
      reversed by E supplementation in the heart but not in the kidneys, although
      combined administration with ARB reversed it in the kidney (p < 0.01).
      Transthoracic echocardiogram showed decreased ejection fraction by OVX and it was
      reversed by E supplementation and administration of ARB. Pathological changes of
      the kidney showed that E supplementation produced thrombotic microangiopathic
      lesions in the glomeruli. These changes were reversed by concomitant
      administration of ARB. CONCLUSION: Although estrogen appears to protect the
      development of cardiac remodeling and heart failure, it promotes microangiopathy
      in the kidney due to thrombosis. Concomitant administration of estrogen and ARB
      might be effective for protection of the heart and the kidney in OVX DSS rats
      with CHF.

PMID- 18097134
TI  - Nocturnal hypertension is associated with an exacerbation of the endothelial
      damage in preeclampsia.
AB  - BACKGROUND: Non-dipping pattern of circadian blood pressure in preeclampsia is
      associated with an increased risk of cardiovascular disease. The pathogenetic
      mechanisms of this relationship are still unclear. We investigated whether non
      dipping in preeclampsia could relate to endothelial activation or damage.
      METHODS: Participants, 20 women with normal pregnancy (mean age 29.9 +/- 5.7
      years) and 31 women with preeclampsia (mean age 29.1 +/- 5.1 years), underwent 24
      hour ambulatory blood pressure monitoring. Plasma levels of von Willebrand factor
      (vWf), marker of endothelial damage and of soluble adhesion molecules (sVCAM-1,
      sICAM-1), and markers of endothelial activation were determined using
      commercially available enzyme-linked immunoassays. RESULTS: Based on whether the
      nocturnal mean arterial pressure (MAP) relative to the daytime MAP declined by
      less than 10%, 21 women with preeclampsia were categorized as non-dippers.
      Compared to healthy pregnant women, patients with preeclampsia showed
      significantly enhanced levels of vWf (206.9 +/- 40.6 vs. 123 +/- 24 IU/dl;p<0.01)
      and sVCAM-1 (2,269 +/- 426 vs.1,159.8 +/- 340 ng/ml; p < 0.01). In addition,
      significantly higher levels of vWf (224.5 +/- 34.9 vs. 170 +/- 23 IU/dl; p <
      0.01) and sVCAM-1 (2,405 +/- 421.4 vs. 1,983 +/- 276.7 ng/ml; p = 0.007) were
      determined, when women with preeclampsia and nocturnal hypertension (non-dippers)
      were compared to dippers. The results were similar even after adjustment for
      severity of preeclampsia. In contrast, neither preeclampsia nor dipping status
      had an effect on sICAM-1 levels. CONCLUSION: Nocturnal hypertension in
      preeclampsia is associated with elevated levels of molecules related to
      endothelial damage. Endothelial damage is a recognized pathogenetic factor for
      atherosclerosis and history of preeclampsia is a risk factor for cardiovascular
      disease. In this context, possible clinical implications of our findings deserve
      further investigation.

PMID- 18097135
TI  - Creatinine-based glomerular filtration rates and microalbuminuria for detecting
      metabolic abnormalities in US adults: the National Health and Nutrition
      Examination Survey 2003-2004.
AB  - BACKGROUND/AIMS: Guidelines suggest searching for metabolic complications of
      chronic kidney disease when glomerular filtration rates (GFR) or urinary albumin
      tests are abnormal. This study aimed to quantify diagnostic test characteristics
      of these measures for detecting metabolic abnormalities. METHODS: Subjects were
      participants aged >or=20 years (n = 7,778) in the US National Health and
      Nutrition Examination Survey 2003-2004. Low GFR was defined as creatinine-based
      estimate <60 ml/min per 1.73 m(2); abnormal urinary albumin-creatinine ratio as
      >or=20 mg/dl in men, >or=30 mg/dl in women; and metabolic abnormalities as
      abnormal potassium, hemoglobin, bicarbonate, phosphorus, or parathyroid hormone
      levels. RESULTS: Of adults, 5.66% had low GFR and 8.14% abnormal urinary albumin
      creatinine ratio. Overall, 15.09% had >or= one metabolic abnormality, as did
      34.07% with low GFR (p < 0.0001) and 24.27% with abnormal urinary albumin
      creatinine ratio (p = 0.0021). Considered as a diagnostic test, the sensitivity,
      specificity, and positive and negative predictive values of low GFR for detecting
      >or=1 metabolic abnormality were 0.13, 0.96, 0.34, and 0.86, respectively.
      Corresponding values for abnormal urinary albumin-creatinine ratio were 0.13,
      0.92, 0.24, and 0.86. CONCLUSIONS: A policy of searching for metabolic
      complications in every adult with low GFR or microalbuminuria has limited
      diagnostic yield.

PMID- 18097136
TI  - Vascular endothelial growth factor protein expression in a renal ablation rabbit
      model under prolonged warm and cold ischemia.
AB  - BACKGROUND/AIMS: To establish a potential correlation between renal and systemic
      production of vascular endothelial growth factor (VEGF) protein after prolonged
      ischemia in a renal ablation model under normothermic and hypothermic conditions.
      METHODS: 38 uninephrectomized New Zealand rabbits were divided into 5 groups. The
      rabbits of each group underwent partial nephrectomy under 90 and 60 min of warm
      and 90 and 120 min of cold ischemia, except for the sham group (S), which served
      as control. Serum creatinine (SCr) and blood-urea-nitrogen (BUN) levels were
      assessed. On the 15th postoperative day (POD), the animals were euthanized and
      the remaining kidneys were evaluated. VEGF immunohistochemistry and serum Western
      blot analysis were performed. RESULTS: In comparison to the control group, groups
      60W, 90C and 120C showed 1.6-, 1.14- and 1.75-fold decreases, respectively, while
      the production of VEGF was significantly declined by 7.4-fold in group 90W (p <
      0.05). Immunohistochemistry revealed prominent VEGF staining in the above
      mentioned three groups, while in group 90W staining was negative. Serum
      biochemistry and microscopic evaluation verified the same differentiation.
      CONCLUSION: Renal and serum VEGF seem to have an analogous expression under
      conditions of prolonged ischemia. VEGF is overexpressed in hypothermic conditions
      compared to warm ischemia exceeding 60 min. Hypothermia can be more advantageous
      in a procedure applying prolonged ischemia.

PMID- 18097137
TI  - Cholesterol-lowering and antioxidant status-improving efficacy of germinated
      giant embryonic rice (Oryza sativa L.) in high cholesterol-fed rats.
AB  - BACKGROUND/AIMS: The purpose of the current study is to investigate the influence
      of germinated giant embryonic rice consumption on the lipid metabolism and
      antioxidant system in rats fed a high-cholesterol diet. METHODS: Four groups of
      rats were given a diet containing 1 g cholesterol/kg for 5 weeks. The control
      group only received a high-cholesterol diet, while the other 3 experimental
      groups received each of the diets made of germinated giant embryonic rice, giant
      embryonic rice, or conventional brown rice (hereafter referred to as GGE-D, GE-D,
      and BR-D, respectively). Plasma and hepatic lipid profiles were measured, and the
      antioxidant status of liver was examined. RESULTS: The plasma HDL-cholesterol
      concentration was significantly higher in rats fed GGE-D compared with the source
      material (GE-D) or BR-D, while there were no differences in the plasma total
      cholesterol and triglyceride concentrations between the groups. Consequently, the
      atherogenic indices of the GGE-D and GE-D groups were significantly lower than
      for the other groups. The plasma and hepatic thiobarbituric acid-reactive
      substance levels were higher in rats in the order of those fed BR-D > GE-D > GGE
      D. While superoxide dismutase and catalase were significantly activated in rats
      fed both GGE-D and GE-D, glutathione peroxidase was significantly and most
      effectively activated in those fed GGE-D. CONCLUSIONS: The current results
      indicate that consumption of germinated giant embryonic rice is effective in
      lowering atherosclerosis cardiovascular disease risk.

PMID- 18097138
TI  - Total plasma homocysteine in hospitalized elderly: associations with vitamin
      status and renal function.
AB  - AIMS: To describe the prevalence of hyperhomocystein- emia (>15 micromol/l) in
      hospitalized elderly and to investigate whether nutrition status and other
      factors are related to total plasma homocysteine (tHcy). METHODS: Sixty
      hospitalized elderly patients (age 83.0 +/- 7.9 years) participated in this cross
      sectional study. Blood was drawn in fasting state and analyzed for albumin,
      prealbumin, lymphocytes, tHcy, cystatin C, folic acid, and vitamin B(12). The
      nutritional status was assessed. Statistical analyses included multivariate
      regression. RESULTS: The prevalence of hyperhomocysteinemia was 31.7%, increased
      cystatin C was observed in 38.3% of the subjects. tHcy correlated positively with
      cystatin C, but negatively with vitamin B(12) and folic acid. Neither age nor
      nutritional status were related to tHcy. In multivariate analysis, folic acid and
      cystatin C remained significant predictors of tHcy (adjusted R(2) = 60.6%).
      According to the regression model, serum folic acid concentrations >30.3 nmol/l
      are required to achieve a mean tHcy <15.0 micromol/l in patients with reduced
      renal function. CONCLUSIONS: Hyperhomocysteinemia is frequent in hospitalized
      elderly. Cystatin C and folic acid explain most of the tHcy variance. Higher
      folic acid levels within the normal range might further decrease tHcy. The
      current lower folic acid cutoff value (7 nmol/l) might not be sufficient in
      preventing homocysteinemia in hospitalized elderly with reduced renal function.

PMID- 18097139
TI  - Ethical and legal implications in seeking and providing a second medical opinion.
AB  - Ethical and legal implications arise both when seeking a second medical opinion
      and when providing one. There has been debate as to whether a second opinion for
      a patient is a right or a concession and whilst today most would consider it to
      be a patient's right, there are nevertheless some disadvantages associated with
      seeking a second opinion. This article addresses the reasons why patients seek
      second opinions, it considers when physicians themselves should refer patients
      and it covers the issues involved in providing a second opinion particularly in
      cases where there is the potential for an allegation of malpractice. Finally, the
      arguments for and against treating patients who are referred for a second opinion
      are addressed. This paper has been prepared following a round table discussion on
      this subject, which was addressed during a symposium on Ethics in
      Gastroenterology and Digestive Endoscopy held in Kos in 2006.

PMID- 18097140
TI  - Do we present abstracts on ethical, legal, cost-effectiveness and patient care
      issues at major gastroenterology congresses?
AB  - INTRODUCTION: In the era of the new millennium, a lot of preclinical and clinical
      research is published. However, ethico-legal, cost-effectiveness and patient care
      issues are not addressed equally. AIM: To investigate whether abstracts presented
      at major international gastroenterology congresses refer to issues relevant to
      doctor-patient relationship, cost-effectiveness and care. METHODS: We reviewed
      the abstracts on disk CD-ROMs of the United European Gastroenterology Week (UEGW)
      and the Digestive Disease Week (DDW), for the years 1998-2006. We used the
      following keywords: ethical/ethically, legal, consent, cost
      effective/effectiveness, care, quality and tolerable/tolerability. RESULTS: Over
      the study period, 1,612/20,018 (8.05%) and 764/45,628 (1.67%) abstracts including
      the above keywords were presented at UEGW and DDW congresses (p = 0.013),
      respectively. Statistically significant more abstracts containing separately any
      of the key words (apart from 'legal') were presented at the UEGW than at the DDW
      congress. There was a significant trend of increased referring to these key words
      over the study period for UEGW (p < 0.041) but not for DDW congresses (p = 0.70).
      CONCLUSION: The abstracts presented at the UEGW refer to ethico-legal, cost
      effectiveness and patient care issues more frequently than those presented at the
      DDW. There is a trend of increased referring to these subjects at the UEGW but
      not at the DDW.

PMID- 18097141
TI  - Prevalence of cognitive and functional impairment in a community sample from Sao
      Paulo, Brazil.
AB  - AIMS: To present the prevalence of cognitive and functional impairment (CFI) in
      community-dwelling elderly subjects from the city of Sao Paulo. METHODS: The
      population was aged 60 years and older (n = 1,563; 68.7% women and 31.3% men) and
      lived in different socioeconomic areas. The following instruments were
      administered to the elderly: the Mini Mental State Examination and the Fuld
      Object Memory Evaluation. The Informant Questionnaire on Cognitive Decline in the
      Elderly and the Bayer-Activities of Daily Living scale were administered to an
      informant. RESULTS: The prevalence of CFI (n = 250) was 16% (95% confidence
      interval, CI: 14.2-17.8%) or 15.8% (95% CI: 13.8-17.8%). In regression models,
      the increase in the odds ratio (OR) of CFI was associated with age, for elderly
      individuals aged 75 years or older, illiterates or with 1-4 years of schooling,
      and with a history of stroke and diabetes mellitus. On the other hand, for
      subjects with a tumor history, the OR of CFI was significantly reduced.
      CONCLUSION: CFI was high and increased at older ages and in subjects with low
      education. Potentially changeable factors were identified (stroke and diabetes),
      and the possible 'protective effect' of tumor/cancer against CFI should be
      further investigated by longitudinal studies.

PMID- 18097142
TI  - Cerebrospinal fluid/serum IgG index is correlated with medial temporal lobe
      atrophy in Alzheimer's disease.
AB  - BACKGROUND/AIM: Intrathecal inflammation has been suggested to play an important
      role in the pathogenesis of Alzheimer's disease (AD). However, there is little
      clinical evidence in support of this hypothesis in AD patients. We previously
      reported that the blood-brain barrier permeability represented by the
      cerebrospinal fluid/serum albumin ratio correlates with medial temporal lobe
      atrophy (MTA) in AD. The aim of this study was to elucidate the relationship
      between intrathecal inflammation and the severity of AD. METHODS: We investigated
      the correlations between the cerebrospinal fluid/serum IgG index and the indices
      of AD severity, including Clinical Dementia Rating and Mini-Mental State
      Examination, and MTA on magnetic resonance imaging in 42 AD patients. Further,
      the number of apolipoprotein E isoforms and the blood-brain barrier permeability
      were also examined for the correlation with the IgG index. RESULTS: The IgG index
      showed a positive correlation with the severity of MTA but not with the other
      parameters examined. CONCLUSION: Our results suggest that intrathecal
      inflammation increases in association with the severity of MTA in AD.

PMID- 18097143
TI  - Asthma, eczema, rhinitis and the risk for dementia.
AB  - BACKGROUND: Inflammation is associated with Alzheimer's disease (AD) and
      dementia. In light of the chronic inflammatory properties of the atopic disorders
      asthma, eczema and rhinitis, we hypothesized an association with dementia.
      METHODS: Self-reported asthma, eczema or rhinitis was assessed (prior to dementia
      follow-up) through questionnaires in the 1960s or 1970s in twins from the
      population-based Swedish Twin Registry. Dementia was assessed both longitudinally
      (n = 22,188), through linkages to two population-based registers, and cross
      sectionally (n = 7,800), through telephone cognitive screening followed by a
      clinical evaluation of suspects of dementia. Risk ratios were estimated with Cox
      and logistic regression models controlling for vascular disease and genetic
      confounding. RESULTS: In the longitudinal study, a history of atopy was
      positively associated with dementia (HR = 1.16; 1.01-1.33). In the cross
      sectional study we found overall lower risks, none of which was statistically
      significant. Asthma was associated with a shorter survival time following AD
      onset. CONCLUSIONS: Atopy is associated with a modestly increased risk of AD and
      dementia that is not mediated by vascular disease or due to genetic confounding.
      A history of asthma is associated with shorter life expectancy after AD
      diagnosis.

PMID- 18097144
TI  - Perceptions and beliefs concerning gastroesophageal reflux disease: physicians
      and patients disagree.
AB  - BACKGROUND/AIM: There is insufficient evidence to support an association between
      lifestyle and gastroesophageal reflux disease (GERD). Furthermore, perceptions
      concerning the impact of GERD on lifestyle are largely unknown. We aimed at
      investigating physicians' perceptions about GERD and lifestyle and at evaluating
      physician-patient agreement concerning the impact of GERD on the quality of life.
      METHODS: A questionnaire was mailed to all Danish primary care physicians (n =
      3,603, response rate 36%) and to all Danish gastroenterologists (n = 624,
      response rate 50%). Another questionnaire was completed by 176 GERD patients on
      medical therapy (84% on proton pump inhibitors). RESULTS: 35% of the physicians
      believe GERD is predominantly caused by lifestyle and 51% always recommend
      lifestyle modifications. According to the physicians, the three most frequently
      affected aspects of quality of life were sleep disturbances (24%), limitations in
      physical activities (22%) and tiredness (18%). However, according to the
      patients, the three most frequently reported aspects were dietary restrictions
      (63%), tiredness/lack of energy (49%) and health concerns (44%). 70% of the
      physicians considered complete absence of symptoms as a useful goal for therapy.
      72% of the patients reported recent symptoms, despite therapy and self-imposed
      lifestyle restrictions. CONCLUSIONS: Physicians and GERD patients disagree on
      impairments of quality of life. Many patients reported frequent symptoms despite
      therapy and self-imposed lifestyle restrictions.

PMID- 18097145
TI  - Effects of locally applied 5-fluorouracil on the prevention of postmastectomy
      seromas in a rat model.
AB  - BACKGROUND: Seroma formation is the most common complication following mastectomy
      and axillary dissection (AD). Currently available interventions have aimed at
      obliterating dead space by inducing fibrosis and through various mechanical
      methods. Here, 5-fluorouracil (5-FU), used as a sclerosing agent for the
      prevention of seroma formation, was investigated in a rat mastectomy model.
      METHODS: 20 rats were divided into two groups (5-FU and control). All rats
      underwent mastectomy and AD. Immediately following the operation, equal volumes
      of saline and 5-FU were administered under the surgical flaps. One week after the
      operation, seroma formation and wound-healing processes were evaluated using
      histopathological and biochemical investigations. RESULTS: 5-FU did not act as a
      sclerosing agent, yet it was highly effective in preventing seroma formation. The
      intensity of acute inflammation, vascularity, as well as leukocyte and fibroblast
      infiltration, were significantly lower in the 5-FU group than the control; the
      tissue collagen fractions and total seroma collagen contents were found to be
      similar between the two groups. CONCLUSIONS: The mechanisms underlying seroma
      prevention by 5-FU are probably related to a decrease in the inflammation and
      angiogenesis rather than a local fibrotic process. Seroma formation may be due to
      a prolonged inflammatory phase of wound healing.

PMID- 18097146
TI  - Poly-N-acetyl glucosamine nanofibers regulate endothelial cell movement and
      angiogenesis: dependency on integrin activation of Ets1.
AB  - Poly-N-acetyl glucosamine (pGlcNAc) nanofiber-derived materials effectively
      achieve hemostasis during surgical procedures. Treatment of cutaneous wounds with
      pGlcNAc in a diabetic mouse animal model causes marked increases in cell
      proliferation and angiogenesis. We sought to understand the effect of the pGlcNAc
      fibers on primary endothelial cells (EC) in culture and found that pGlcNAc
      induces EC motility. Cell motility induced by pGlcNAc fibers is blocked by
      antibodies directed against alphaVbeta3 and alpha5beta1 integrins, both known to
      play important roles in the regulation of EC motility, in vitroand in vivo.
      pGlcNAc treatment activates mitogen-activated protein kinase and increases Ets1,
      vascular endothelial growth factor (VEGF) and interleukin 1 (IL-1) expression.
      pGlcNAc activity is not secondary to its induction of VEGF; inhibition of the
      VEGF receptor does not inhibit the pGlcNAc-induced expression of Ets1 nor does
      pGlcNAc cause the activation of VEGF receptor. Both dominant negative and RNA
      interference inhibition of Ets1 blocks pGlcNAc-induced EC motility. Antibody
      blockade of integrin results in the inhibition of pGlcNAc-induced Ets1
      expression. These findings support the hypothesis that pGlcNAc fibers induce
      integrin activation which results in the regulation of EC motility and thus in
      angiogenesis via a pathway dependent on the Ets1 transcription factor and
      demonstrate that Ets1 is a downstream mediator of integrin activation.

PMID- 18097147
TI  - Insulin activates ATP-sensitive potassium channels via phosphatidylinositol 3
      kinase in cultured vascular smooth muscle cells.
AB  - The effects of insulin on the vasculature are significant because insulin
      resistance is associated with hypertension. To increase the understanding of the
      effects of insulin on the vasculature, we analyzed changes in potassium ion
      transport in cultured vascular smooth muscle cells (VSMCs). Using the potential
      sensitive fluorescence dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol
      [DiBAC4(3)], we found that insulin induced membrane hyperpolarization after 2 min
      in A10 cells. Insulin-induced hyperpolarization was suppressed by glibenclamide,
      an ATP-sensitive potassium (K(ATP)) channel blocker. Using a cell-attached patch
      clamp experiment, the K(ATP) channel was activated by insulin in both A10 cells
      and isolated VSMCs from rat aortas, indicating that insulin causes membrane
      hyperpolarization via K(ATP) channel activation. These effects were not dependent
      on intracellular ATP concentration, but wortmannin, a phosphatidylinositol 3
      kinase (PI3-K) inhibitor, significantly suppressed insulin-induced K(ATP) channel
      activation. In addition, insulin enhanced phosphorylation of insulin receptor,
      insulin receptor substrate (IRS)-1 and protein kinase B (Akt) after 2 min. These
      data suggest that K(ATP) channel activation by insulin is mediated by PI3-K.
      Furthermore, using a nitric oxide synthase (NOS) inhibitor, we found that NOS
      might play an important role downstream of PI3-K in insulin-induced K(ATP)
      channel activation. This study may contribute to our understanding of mechanisms
      of insulin resistance-associated hypertension.

PMID- 18097148
TI  - Different risk factors for vascular calcification in end-stage renal disease
      between diabetics and nondiabetics: the respective importance of glycemic and
      phosphate control.
AB  - Vascular calcification is highly prevalent in dialysis patients, and
      significantly increases cardiovascular mortality. The presence and progression of
      vascular calcification is significantly associated with chronic inflammation and
      malnutrition. Disorders of mineral metabolism, particularly hyperphosphatemia,
      have been emphasized as risk factors for vascular calcification. Although
      vascular calcification has been reported to be highly prevalent in diabetic
      patients with end-stage renal disease (ESRD), the risk factors for vascular
      calcification in these patients have not been fully explored. Through a review of
      the literature and our recent studies examining vascular calcification in ESRD
      patients, hyperphosphatemia is significantly associated with vascular
      calcification in nondiabetic ESRD patients, while it may not be a significant
      risk factor for vascular calcification in diabetic ESRD patients. In diabetic
      patients, vascular calcification occurs long before the initiation of dialysis
      therapy, and the factors associated with vascular calcification in non-uremic
      diabetics appear to be hyperglycemia and related metabolic disorders, such as
      increased glycation and oxidative stress. In diabetic ESRD patients,
      hyperglycemia is also suggested to be a significant factor associated with the
      progression of vascular calcification. Thus, the importance of glycemic and
      phosphate control is suggested to be emphasized in diabetic and nondiabetic ESRD
      patients, respectively, for prevention of the progression of vascular
      calcification.

PMID- 18097149
TI  - Atherosclerotic renal artery stenosis: association with emerging vascular risk
      factors.
AB  - BACKGROUND: The established risk factors for atherosclerotic renal artery
      stenosis (ARAS) include hypertension, diabetes mellitus, dyslipidemia, obesity,
      smoking, old age and family history. In the last few years, several emerging risk
      factors have been proposed as predictors of ARAS, namely homocysteine,
      fibrinogen, C-reactive protein, lipoprotein(a) and creatinine. METHODS: We
      searched Pubmed/Medline for studies investigating the prognostic value of each of
      these emerging risk factors in ARAS. RESULTS: Creatinine and C-reactive protein
      seem to be the most promising predictors of ARAS, whereas the prognostic value of
      homocysteine, lipoprotein(a) and fibrinogen is not yet fully determined.
      CONCLUSION: The establishment of a definite role for these emerging risk factors
      could result in earlier recognition and/or better management of ARAS with
      potential regression/slowing down of progression of stenosis. Modifying these
      markers may also improve the therapeutic approach of the associated systemic
      atherosclerosis in these high-risk patients. Future trials should focus on the
      effect of different classes of drugs (e.g. statins and fibrates) on the levels of
      the emerging risk factors and the association with ARAS progression.

PMID- 18097150
TI  - STAT3 inhibits apoptosis of human renal tubular epithelial cells induced by ATP
      depletion/recovery.
AB  - BACKGROUND/AIMS: Apoptosis has been implicated in renal ischemic injury, the
      regulating mechanism of which is still unclear. Signal transducers and activators
      of transcription (STAT) participate in inflammation, apoptosis, and
      tumorigenesis. In the in vitro model of renal ischemic injury, we explored the
      role of the STAT3, a major component of the STAT family, in apoptosis of human
      proximal tubular epithelial cell (HKC) induced by ATP depletion/recovery.
      METHODS: Apoptosis of HKC was induced in an in vitro model of acute renal
      failure. STAT3 activation was analyzed by Western blotting. RNA interference was
      used to knock down STAT3 expression. The effect of STAT3 knockdown or STAT3C
      overexpression on apoptosis was assessed by annexin V binding and propidium
      iodide uptake. RESULTS: STAT3 was phosphorylated during the course of ATP
      depletion-induced HKC cell apoptosis. STAT3 knockdown suppressed STAT3
      phosphorylation, and promoted apoptosis of HKC subjected to ATP
      depletion/recovery, while STAT3C overexpression conferred resistance of HKC to
      ATP depletion-induced apoptosis. CONCLUSION: Our results demonstrated that STAT3
      mediates resistance to ATP depletion-induced apoptosis of HKC, which may be a
      potential target in treatment of renal ischemic injury.

PMID- 18097151
TI  - Serum troponin in neonatal intensive care.
AB  - Cardiac troponins have a major role in screening and diagnosis of myocardial
      ischaemia in adults and children. Their introduction has redefined the diagnosis
      of myocardial infarction in adults and provided valuable prognostic information.
      In the paediatric population, troponins show a good correlation with the extent
      of myocardial damage following cardiac surgery and cardiotoxic medication, and
      can be used as predictors of subsequent cardiac recovery and mortality. This
      review discusses the current established reference values in term and preterm
      infants and demonstrates their potential use in neonatology. They may serve as a
      useful adjunct in the assessment of the magnitude of myocardial injury in
      respiratory distress syndrome and asphyxia. They may also benefit centres without
      on-site echocardiography with some evidence showing good correlation with echo
      derived markers of myocardial function. The use of troponins in the neonatal unit
      remains a research tool. More work is needed to explore their prognostic role and
      monitoring response to treatment following cardioprotective strategies. In
      preterm infants the effect of inotropes on myocardial function needs further
      study and troponin may form an integral part of this research.

PMID- 18097152
TI  - Cytokine expression in response to bacterial antigens in preterm and term infant
      cord blood monocytes.
AB  - BACKGROUND: Neonatal susceptibility to bacterial infection is associated with an
      immature immune system, but the role of different bacterial antigens in specific
      responses is largely unknown. OBJECTIVE: To evaluate differences in intracellular
      cytokine response to physiologically relevant bacterial antigens in term and
      preterm infants as compared with adults. METHODS: Cord blood samples from preterm
      and term neonates and adult peripheral blood samples were cultured ex vivo with
      and without whole heat-killed bacteria. Intracellular leukocyte production of
      interleukin (IL)-6, IL-10, IL-12, and IL-8 responses was assessed by flow
      cytometry. RESULTS: Monocytes were the primary producers of all mediators.
      Escherichia coli was the most potent stimulant. Lactobacillus plantarum 299v
      activated fewer monocytes as compared with E. coli for all responses (p < 0.05),
      except for IL-12 in term neonates. IL-6 response to Staphylococcus epidermidis
      was lower in both groups of neonates as compared with adults (p = 0.023 and p =
      0.001). IL-8 response to S. epidermidis was lower in term as compared with
      preterm neonates and adults (p = 0.003). IL-10 response to group B streptococci
      was lower in term neonates as compared with adults and higher in preterm as
      compared with term neonates (p = 0.015). CONCLUSIONS: Monocytes from term
      neonates compared to preterm neonates show a downregulated anti-inflammatory
      response to specific bacteria. High neonatal response to pathogenic E. coli in
      the preterm infant could cause uncontrolled inflammatory response, while lower IL
      6 response to S. epidermidis in neonates may indicate a basis for vulnerability
      to S. epidermidis infection.

PMID- 18097153
TI  - Utility of the rapid B-type natriuretic peptide assay for detection of
      cardiovascular problems in newborn infants with respiratory difficulties.
AB  - BACKGROUND: Because the major problems of respiratory difficulties in newborn
      infants are due to cardiopulmonary problems, improving the early detection and
      referral of newborn infants with cardiovascular problems has been considered one
      of the primary goals of care in the neonatal intensive care unit. OBJECTIVE: To
      evaluate whether rapid plasma B-type natriuretic peptide (BNP) assay could be
      used as a screening test to detect the cardiovascular problems in newborn infants
      with respiratory difficulties. METHODS: We studied 73 newborn infants >or=34
      weeks gestational age presenting with respiratory difficulties during the first
      few days after birth; they were divided into a cardiovascular problem group (CP
      group, n = 32) and a noncardiac problem group (NP group, n = 41) according to the
      presence of cardiovascular problems by clinical and/or echocardiographic studies
      in newborn infants with respiratory difficulties. RESULTS: On admission, the
      median (25-75%) BNP concentration of the CP group was significantly higher than
      that of the NP group [1,038 (578-1,435) vs. 240 (118-388) pg/ml, p < 0.001]. The
      best cutoff BNP values for differentiating the CP group were 346.0, 421.0, 570.5
      and 191.5 pg/ml within 18 h, at 18-36 h, at 36-60 h and after 60 h of life,
      respectively. Although the plasma BNP measurement was not a single confirmative
      test, it was found to have a high sensitivity and a high negative predictive
      value for rapidly ruling out serious cardiovascular problems in neonatal
      respiratory difficulties. CONCLUSION: A rapid plasma BNP assay may be useful for
      detection of cardiovascular problems in newborn infants with respiratory
      difficulties during the first few days after birth.

PMID- 18097154
TI  - PENN neurodegenerative disease research - in the spirit of Benjamin Franklin.
AB  - Benjamin Franklin (1706-1790) was entrepreneur, statesman, supporter of the
      public good as well as inventor, and his most significant invention was the
      University of Pennsylvania (PENN). Franklin outlined his plans for a college
      providing practical and classical instruction to prepare youth for real-world
      pursuits in his 'Proposals Relating to the Education of Youth in Pensilvania'
      (1749), and Franklin's spirit of learning to serve society guides PENN to the
      present day. This is evidenced by the series of articles in this special issue of
      Neurosignals, describing research conducted by seasoned and newly recruited PENN
      faculty, addressing consequences of the longevity revolution which defines our
      epoch at the dawn of this millennium. While aging affects all organ systems, the
      nervous system is most critical to successful aging. Thus, the articles in this
      special issue of Neurosignals focus on research at PENN that is designed to
      prevent or ameliorate aging-related neurodegenerative disorders such as
      Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis and
      frontotemporal dementia. This research could enhance our chances of aging
      successfully in the continuing longevity revolution, and the essay here provides
      context and background on this research.

PMID- 18097155
TI  - Biomarkers for early detection of Alzheimer pathology.
AB  - The increasing prevalence of Alzheimer's disease and the devastating consequences
      of late-life dementia motivates the drive to develop diagnostic biomarkers to
      reliably identify the pathology associated with this disorder. Strategies to
      accomplish this include the detection of altered levels of tau and amyloid in
      cerebrospinal fluid, the use of structural MRI to identify disease-specific
      patterns of regional atrophy and MRI T(1)rho to detect disease-related
      macromolecular protein aggregation, and the direct imaging of amyloid deposits
      using positron emission tomography and single photon emission computerized
      tomography. Success will facilitate the ability to reliably diagnose Alzheimer's
      disease while the symptoms of brain failure are mild and may provide objective
      measures of disease-modifying treatment efficacy.

PMID- 18097156
TI  - PENN biomarker core of the Alzheimer's disease Neuroimaging Initiative.
AB  - There is a pressing need to develop effective prevention and disease-modifying
      treatments for Alzheimer's disease (AD), a dreaded affliction whose incidence
      increases almost logarithmically with age starting at about 65 years. A key need
      in the field of AD research is the validation of imaging and biochemical
      biomarkers. Biomarker tests that are shown to reliably predict the disease before
      it is clinically expressed would permit testing of new therapeutics at the
      earliest time point possible in order to give the best chance for delaying the
      onset of dementia in these patients. In this review the current state of AD
      biochemical biomarker research is discussed. A new set of guidelines for the
      diagnosis of AD in the research setting places emphasis on the inclusion of
      selected imaging and biochemical biomarkers, in addition to neuropsychological
      behavioral testing. Importantly, the revised guidelines were developed to
      identify patients at the earliest stages prior to full-blown dementia as well as
      patients with the full spectrum of the disease. The Alzheimer's Disease
      Neuroimaging Initiative is a multicenter consortium study that includes as one of
      its primary goals the development of standardized neuroimaging and biochemical
      biomarker methods for AD clinical trials, as well as using these to measure
      changes over time in mildly cognitively impaired patients who convert to AD as
      compared to the natural variability of these in control subjects and their
      further change over time in AD patients. Validation of the biomarker results by
      correlation analyses with neuropsychological and neurobehavioral test data is one
      of the primary outcomes of this study. This validation data will hopefully
      provide biomarker test performance needed for effective measurement of the
      efficacy of new treatment and prevention therapeutic agents.

PMID- 18097157
TI  - Cognitive impairment in Parkinson's disease and dementia with lewy bodies: a
      spectrum of disease.
AB  - Parkinson's disease (PD) is classically thought of as a movement disorder
      characterized by tremor, rigidity and postural instability. Nevertheless, there
      is growing recognition of prominent cognitive impairment in PD and related
      disorders, which is responsible for substantial disability in these patients.
      This review will focus on cognitive impairment associated with Lewy body
      pathology, including PD with dementia (PDD) and dementia with Lewy bodies (DLB).
      We will review the epidemiology, clinical evaluation, underlying mechanisms and
      treatment of cognitive impairment in these patients. Despite differences between
      PDD and DLB, there is clinical, neuropathological and radiological overlap
      between these disorders, supporting the view that they represent a spectrum of
      disease. These observations suggest that common targets for diagnosis and
      treatment of these disorders can be identified.

PMID- 18097158
TI  - Olfactory dysfunction in Parkinson's disease.
AB  - Prior to the onset of the cardinal motor features of idiopathic Parkinson's
      disease (PD), other manifestations of neurodegeneration such as olfactory
      dysfunction are often apparent. Characterizing these potential biomarkers of
      preclinical PD is particularly important in identifying individuals who will go
      on to develop disabling symptoms, and thus be good candidates for new
      neuroprotective strategies. As shown by the Braak neuropathologic staging of PD,
      the olfactory system is among the first neuronal populations to display Lewy body
      pathology. Clinically, loss of smell can be easily tested in the office using
      several validated techniques and is often helpful to the physician in
      distinguishing idiopathic PD from other forms of parkinsonism. Recent findings
      have indicated that a decline in olfaction may be observed in selected at-risk
      patients, which has significant implications for identifying potential study
      populations. Ongoing studies of olfactory dysfunction may also reveal potential
      for use as a medication-independent biomarker of disease progression in addition
      to use as a biomarker for the diagnosis of PD.

PMID- 18097159
TI  - TDP-43 proteinopathies: neurodegenerative protein misfolding diseases without
      amyloidosis.
AB  - In this review, we summarize recent advances in understanding frontotemporal
      lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and related
      neurodegenerative disorders that are collectively known as TDP-43
      proteinopathies, since transactive response DNA-binding protein 43 (TDP-43) was
      recently shown to be the major component of the ubiquitinated inclusions that are
      their pathological hallmarks. TDP-43 proteinopathies are distinct from most other
      neurodegenerative disorders because TDP-43 inclusions are not amyloid deposits.
      Besides TDP-43-positive inclusions, both sporadic and familial forms of FTLD and
      ALS have the pathologic TDP-43 signature of abnormal hyperphosphorylation,
      ubiquitination and C-terminal fragments in affected brain and spinal cord,
      suggesting that they share a common mechanism of pathogenesis. Thus, these
      findings support the concept that FTLD and ALS represent a clinicopathologic
      spectrum of one disease, that is, TDP-43 proteinopathy.

PMID- 18097160
TI  - Beer and bread to brains and beyond: can yeast cells teach us about
      neurodegenerative disease?
AB  - For millennia, humans have harnessed the astonishing power of yeast, producing
      such culinary masterpieces as bread, beer and wine. Therefore, in this new
      millennium, is it very farfetched to ask if we can also use yeast to unlock some
      of the modern day mysteries of human disease? Remarkably, these seemingly simple
      cells possess most of the same basic cellular machinery as the neurons in the
      brain. We and others have been using the baker's yeast, Saccharomyces cerevisiae,
      as a model system to study the mechanisms of devastating neurodegenerative
      diseases such as Parkinson's, Huntington's, Alzheimer's and amyotrophic lateral
      sclerosis. While very different in their pathophysiology, they are collectively
      referred to as protein-misfolding disorders because of the presence of misfolded
      and aggregated forms of various proteins in the brains of affected individuals.
      Using yeast genetics and the latest high-throughput screening technologies, we
      have identified some of the potential causes underpinning these disorders and
      discovered conserved genes that have proven effective in preventing neuron loss
      in animal models. Thus, these genes represent new potential drug targets. In this
      review, I highlight recent work investigating mechanisms of cellular toxicity in
      a yeast Parkinson's disease model and discuss how similar approaches are being
      applied to additional neurodegenerative diseases.

PMID- 18097161
TI  - Hsp104: a weapon to combat diverse neurodegenerative disorders.
AB  - Many of the fatal neurodegenerative disorders that plague humankind, including
      Alzheimer's and Parkinson's disease, are connected with the misfolding of
      specific proteins into a surprisingly generic fibrous conformation termed
      amyloid. Prior to amyloid fiber assembly, many proteins populate a common
      oligomeric conformation, which may be severely cytotoxic. Therapeutic innovations
      are desperately sought to safely reverse this aberrant protein aggregation and
      return proteins to normal function. Whether mammalian cells possess any such
      endogenous activity remains unclear. By contrast, fungi, plants and bacteria all
      express Hsp104, a protein-remodeling factor, which synergizes with the Hsp70
      chaperone system to resolve aggregated proteins and restore their functionality.
      Surprisingly, amyloids can also be adaptive. In yeast, Hsp104 directly regulates
      the amyloidogenesis of several prion proteins, which can confer selective
      advantages. Here, I review the modus operandi of Hsp104 and showcase efforts to
      unleash Hsp104 on the protein-misfolding events connected to disparate
      neurodegenerative amyloidoses.

PMID- 18097162
TI  - The role of autophagy in age-related neurodegeneration.
AB  - Most age-related neurodegenerative diseases are characterized by accumulation of
      aberrant protein aggregates in affected brain regions. In many cases, these
      proteinaceous deposits are composed of ubiquitin conjugates, suggesting a failure
      in the clearance of proteins targeted for degradation. The 2 principal routes of
      intracellular protein catabolism are the ubiquitin proteasome system and the
      autophagy-lysosome system (autophagy). Both of these degradation pathways have
      been implicated as playing important roles in the pathogenesis of
      neurodegenerative disease. Here we describe autophagy and review the evidence
      suggesting that impairment of autophagy contributes to the initiation or
      progression of age-related neurodegeneration. We also review recent evidence
      indicating that autophagy may be exploited to remove toxic protein species,
      suggesting novel strategies for therapeutic intervention for a class of diseases
      for which no effective treatments presently exist.

PMID- 18097163
TI  - Motor neuron disease and frontotemporal lobar degeneration: a tale of two
      disorders linked to TDP-43.
AB  - Motor neuron disease (MND) is a neurodegenerative condition long thought to be
      associated only with motor weakness. Recent work now shows that cognitive
      difficulties are present in up to half of the patients with this disorder. About
      5-10% of patients with MND have a frank dementia that resembles frontotemporal
      lobar degeneration (FTLD). Imaging studies show quantitative abnormalities that
      resemble FTLD. Moreover, biochemical studies of ubiquinated histopathologic
      abnormalities in MND and FTLD reveal identical inclusions of TDP-43. These
      findings underline a fundamental link between MND and FTLD. This paper reviews
      this body of work.

PMID- 18097164
TI  - Measuring decision-making capacity in cognitively impaired individuals.
AB  - Cognitive and functional losses are only part of the spectrum of disability
      experienced by persons with Alzheimer's disease and related dementias. They also
      experience losses in the ability to make decisions, known as decision-making
      capacity. Researchers have made substantial progress in developing a model of
      capacity assessment that rests upon the concept of the 4 decision-making
      abilities: understanding, appreciation, choice and reasoning. Empirical research
      has increased our understanding of the effects of late-life cognitive impairment
      on a person's ability to make decisions. This review examines studies of the
      capacity to consent to treatment, research and the management of everyday
      functional abilities. The results illustrate the clinical phenotype of the
      patient who retains the capacity to consent. They also suggest that measures of
      capacity can improve how researchers measure the benefits of cognitive
      enhancements and stage dementia.

PMID- 18097165
TI  - Mutations in LRRK2 as a cause of Parkinson's disease.
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause
      of late-onset Parkinson's disease (PD). Clinical and pathological studies have
      demonstrated that in the majority of cases LRRK2 mutations lead to PD with
      classical clinical and pathological features. However, in some patients the
      pathological features can be distinct and/or more extensive than typically seen
      in PD. Collectively, these findings provide important clues into the mechanisms
      by which LRRK2 mutations can lead to demise of dopaminergic neurons. The
      understanding of LRRK2 protein function and its gene regulation and the
      consequences of mutations are still at their infancy, but scientific findings are
      progressing at a rapid pace. Although more detailed information on LRRK2 is still
      needed in the quest for therapeutic intervention that could halt or slow the
      progression of disease, here we summarize the current information on the
      biological and pathological properties of LRRK2.

PMID- 18097166
TI  - A need to document a role for palliative chemotherapy in the management of
      progressive malignant disease.

PMID- 18097167
TI  - Chemotherapy use and associated factors among cancer patients near the end of
      life.
AB  - OBJECTIVES: We investigated the frequency of chemotherapy use and its associated
      factors in patients in all age groups in the last year of life. METHODS: We
      identified cancer patients who died in 2004 in any of 17 hospitals. We used
      demographic and treatment characteristics by computerized hospital information
      systems and by linking the identification numbers to the 2004 death registry.
      RESULTS: 48.7% of patients in the last 6 months of life, 43.9% in the last 3
      months, and 30.9% in the last month of life received chemotherapy. The frequency
      of chemotherapy use was lower for older patients. In those > or =65 years old,
      there was no difference between women and men in the proportion that received
      chemotherapy. For patients <65 years of age, a larger proportion of women than
      men received chemotherapy, and chemotherapy use was significantly less frequent
      for patients with refractory disease than for those with responsive disease.
      Patients dying at a relatively small hospital without a hospice inpatient unit
      were significantly more likely to receive chemotherapy. CONCLUSIONS: Despite the
      fact that most cancer patients are resistant to chemotherapy at the end of life,
      it was administered often to all age groups.

PMID- 18097168
TI  - Vascular endothelial growth factor partially inhibits the trastuzumab-mediated
      antibody-dependent cellular cytotoxicity of human monocytes.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is produced by almost all
      cancer cells and VEGF receptor 1 (R1) (Flt-1) is abundantly expressed on human
      monocytes. In the present study, we investigated whether VEGF affects the
      antibody-dependent cell-mediated cytotoxicity (ADCC) of human monocytes mediated
      by trastuzumab. METHODS: HER-2-expressing tumor cell lines (MKN-7, TE-4 and SKOV
      3) were evaluated for trastuzumab-mediated ADCC of human monocytes in the
      presence of VEGF(165). The trastuzumab-mediated, monocyte-derived ADCC were
      treated with the anti-human blocking VEGF R1 or VEGF R2 mAb. VEGF-induced
      intracellular signaling on monocytes was quantified with ELISA kits. RESULTS:
      VEGF partially inhibited the ADCC of human monocytes mediated by trastuzumab. The
      VEGF-induced deficiency of human monocytes for ADCC was completely recovered by
      the anti-human blocking VEGF R1 mAb, while the anti-VEGF R2 blocking mAb did not
      have any effect. Furthermore, VEGF treatment enhanced the phospho-Erk 1/2 in
      human monocytes. CONCLUSION: VEGF partially inhibited the ADCC of human monocytes
      mediated by trastuzumab, and this inhibition was mainly mediated by VEGF R1 (Flt
      1).

PMID- 18097169
TI  - Prognostic factors in extrapulmonary small cell carcinomas. A large retrospective
      study.
AB  - BACKGROUND: Extrapulmonary small cell carcinoma (EPSCC) is a heterogeneous group
      of cancers. The clinicopathological features of EPSCC remain poorly defined.
      PATIENTS AND METHODS: Patients with the clinicopathological features of EPSCC,
      treated at three major medical centers in Taiwan, were included. Histologic and
      clinical diagnoses, smoking history, staging, clinical course and treatment
      outcome were reviewed and analyzed. RESULTS: A total of 90 patients, treated
      between 1995 and 2005, were eligible for analysis. Forty-nine patients had
      limited disease and 41 extensive disease. Ten, 18, 17 and 45 patients received no
      treatment, local treatment, chemotherapy alone or combined modality treatment,
      respectively; the median survival for these four groups was 1.1, 13.8, 6.7 and
      24.9 months. The origin of cancer was head and neck in 17, gastrointestinal in
      27, genitourinary in 10, gynecologic in 27 and unknown in 9 patients; the median
      survival time was 34.2, 6.4, 9.1, 23.7 and 9.2 months, respectively. Ten out of
      90 patients were long-term survivors, and 9 of them had tumors of head-and-neck
      and gynecologic origin. There was no statistically significant difference in
      survival between smokers and non-smokers. Factors associated with survival in
      univariate analysis included age < or =60, female gender, limited disease, head
      and-neck and gynecologic origin, as well as combined modality treatment. However,
      in multivariate analysis, only female gender, limited disease and combined
      modality treatment were independent predictors of survival. CONCLUSIONS: Female
      gender, limited disease and combined modality treatment are favorable prognostic
      factors for patients with EPSCC. Prolonged survival is more likely in patients
      with tumors of head-and-neck and gynecologic origin.

PMID- 18097173
TI  - The study of retinal ganglion cell apoptosis induced by different intensities of
      microwave irradiation.
AB  - PURPOSE: To observe the influence on the retinal ganglion cells induced by 2,450
      MHz microwave. The radiant intensities were 10, 30 and 60 mW x cm(-2). METHODS:
      Retinal ganglion cells were cultured in vitro and divided into 4 groups, of which
      3 were exposed to different intensities of microwaves and 1 was the control
      group. The morphological variation of cells was observed by invert microscope.
      The survival rate was assessed by trypan blue. Annexin V-PI 2-color flow
      cytometry was used to detect the percentage of earlier apoptosis cells after
      radiation. RESULTS: The changes in the morphology of all cells were observed
      after radiation. The cell survival rates were reduced and the earlier apoptosis
      increased with growing microwave intensity. CONCLUSIONS: The 2,450-MHz microwave
      will cause damage to retinal ganglion cells in a dose-dependent manner.

PMID- 18097170
TI  - Hepatic arterial infusion chemotherapy with epirubicin in patients with advanced
      hepatocellular carcinoma and portal vein tumor thrombosis.
AB  - OBJECTIVE: The objective of this study was to evaluate the antitumor, survival,
      and adverse effects of hepatic arterial infusion chemotherapy using epirubicin in
      patients with advanced hepatocellular carcinoma and portal vein tumor thrombosis.
      METHODS: The study population comprised 45 consecutive patients with advanced
      hepatocellular carcinoma associated with tumor thrombosis in the main and/or
      first portal vein. A dose of 50-60 mg/m(2) epirubicin was administered from the
      proper, right, or left hepatic artery. Treatment was repeated every 4-12 weeks if
      there was no evidence of tumor progression or unacceptable toxicity. RESULTS: Of
      the 45 treated patients, 4 (9%) achieved a partial response, 12 (27%) had no
      change, and 29 (64%) showed progressive disease. The median survival time, 1-year
      survival rate and median time to progression were 6.0 months, 20.0%, and 1.1
      months for all patients, respectively. The main grade 3 and 4 toxicities were
      leukopenia (27%), neutropenia (47%), thrombocytopenia (9%), and elevation of
      aspartate (36%) and alanine aminotransferases (13%). Febrile neutropenia was
      observed in 2 patients (4%). CONCLUSION: Hepatic arterial infusion chemotherapy
      with epirubicin is well tolerated, but appears to have little activity as a
      single agent in patients with hepatocellular carcinoma and portal vein tumor
      thrombosis.

PMID- 18097174
TI  - Early clinical evaluation of AcrySof ReSTOR multifocal intraocular lens for
      treatment of cataract.
AB  - PURPOSE: To evaluate the efficacy, safety and early visual quality of the AcrySof
      ReSTOR multifocal intraocular lens (IOL) following cataract surgery. SETTING: Eye
      Center of Shandong University of Traditional Chinese Medicine, Jinan Shierming
      Eye Hospital, Jinan, Shandong, China. METHODS: After small-incision
      phacoemulsification, AcrySof ReSTOR IOLs were implanted in 20 subjects (40 eyes,
      ReSTOR group). Monofocal IOLs were implanted in 18 subjects (36 eyes, control
      group). Three to six months following bilateral implantation, visual acuity,
      depth of focus, corneal astigmatism, contrast sensitivity, glare sensitivity,
      visual field and spherical aberration were compared between the groups. A
      subjective outcome questionnaire was also completed by the subjects. RESULTS:
      Uncorrected near visual acuity 0.5 or better was achieved by 92.5% of the ReSTOR
      eyes. In the monofocal eyes, only 33.3% of the eyes achieved uncorrected near
      visual acuity of 0.5 or better. There was no statistical difference between
      corrected near, distance visual acuity, and uncorrected distance visual acuity in
      the 2 groups (p > 0.05). In patients with visual acuity 0.5 or better, the depth
      of focus was 4.87 +/- 1.09 and 2.08 +/- 0.69 dpt in the ReSTOR and control
      groups, respectively. The contrast sensitivity, glare sensitivity and visual
      field of both groups were similar (p > 0.05). The spherical aberration of the 2
      groups was similar (t = -0.37, p = 0.71). Visual disturbances were minimal with
      only 1 patient in each group complaining of glare at night. CONCLUSION: The
      AcrySof ReSTOR multifocal IOL is a safe and effective treatment for cataracts.

PMID- 18097175
TI  - Retinal nerve fiber layer images captured by GDx-VCC in early diagnosis of
      glaucoma.
AB  - OBJECTIVES: To compare differences in retinal nerve fiber layer (RNFL) parameters
      between normal subjects and patients with various degrees of glaucoma, evaluate
      the sensitivity and specificity of GDx-VCC parameters, and determine the
      capability of GDx-VCC parameters and the most valuable indicators for the
      diagnosis of early glaucoma. METHODS: GDx-VCC was used to measure RNFL in 80
      patients with early glaucoma (130 eyes), 70 patients with advanced glaucoma (90
      eyes) and 40 normal controls (80 eyes). All glaucoma patients were divided into
      an early glaucoma group and an advanced glaucoma group, according to the mean
      defect of the visual field. RNFL parameters were compared between normal subjects
      and patients with various degrees of glaucoma. Receiver operating characteristic
      (ROC) curves of GDx parameters were drawn to determine the most valuable GDx
      parameters for the diagnosis of early glaucoma. RESULTS: The RNFLs were
      significantly thinner in patients with early glaucoma than those in normal
      subjects; they were also significantly thinner in patients with advanced glaucoma
      than those in patients with early glaucoma. The differences in all parameters
      reached statistical significance (p < 0.001). The mean defect of the visual field
      was significantly correlated with all RNFL parameters (p < 0.001). The areas
      under the ROC curves were >0.7 for all parameters, which could effectively
      differentiate early glaucoma from normal subjects. The areas under the ROC curves
      were 0.81 for nerve fiber indicator and inferior average with better
      differentiation capability. CONCLUSIONS: GDx-VCC can provide quantitative
      measurements of RNFL thickness for clinical use, which can effectively
      differentiate patients with early glaucoma from normal subjects, and will be
      clinically very helpful for the early diagnosis of glaucoma. Nerve fiber
      indicator and inferior average are the most effective indicators for the early
      diagnosis of glaucoma.

PMID- 18097176
TI  - Adult nasolacrimal sac mucocele.
AB  - Adult nasolacrimal sac mucocele is an uncommon mass arising in the medial canthal
      region of the orbit. Twenty-one cases with lacrimal sac mucocele were reviewed
      retrospectively. We gathered information about the clinical characteristics,
      natural history, mechanism for mucocele formation and optimal management of this
      disorder. The results show that the medial canthal mass was confirmed to be
      dacryo-cystocele-associated with distal nasolacrimal duct obstruction and
      proximal obstruction at the junction of the common canaliculus and sac. The
      interventional procedure of polyurethane stent placement is a practicable and
      simplified treatment for lacrimal sac mucocele.

PMID- 18097177
TI  - The use of orbital radiotherapy for Graves' ophthalmopathy: quantitative review
      of the evidence.
AB  - OBJECTIVE: To systematically evaluate the efficacy of orbital radiotherapy in the
      treatment of Graves' ophthalmology. METHODS: Pertinent studies were selected
      through an electronic search of Cochrane Library, Medline, Embase and Chinese
      Biomedical Database. Studies meeting selected criteria were reviewed
      systematically by meta-analysis. The treatment effect was measured as risk
      difference (RD) of treatment failure, and pooled estimates were computed
      according to a random effect model. RESULTS: A total of 18 studies were included
      in this meta-analysis, 8 cohort and 10 randomized. Orbital radiotherapy alone was
      significantly more effective than a vehicle control [pooled RD = -0.26, 95%
      confidence interval (CI) = -0.41 to -0.10] and as effective as oral
      corticosteroids (pooled RD = -0.10, 95% CI = -0.20 to -0.00). The combination of
      orbital radiotherapy and oral corticosteroids was markedly more effective than
      other treatment modalities (pooled RD = -0.27, 95% CI = -0.36 to -0.17). Orbital
      radiotherapy combined with intravenous methylprednisolone was more efficacious
      than other treatment modalities (pooled RD = -0.18, 95% CI = -0.30 to -0.07).
      CONCLUSIONS: Orbital radiotherapy appears to be an effective treatment for
      Graves' ophthalmology and seems to have an increased effect when given with
      systemic corticosteroids. Orbital radiotherapy combined with intravenous
      methylprednisolone seems to have the best documented efficacy.

PMID- 18097178
TI  - The status of diabetic retinopathy and diabetic macular edema in patients with
      type 2 diabetes: a survey from Beixinjing District of Shanghai city in China.
AB  - Diabetic macular edema (DME) is the major cause of vision loss in patients with
      diabetic retinopathy (DR). The purpose of this study was to assess the prevalence
      of DR and DME in a community in China and to analyze the characteristics of their
      optical coherence tomography (OCT) images. This study was an incidence survey
      based on data from 108,132 residents living in the Beixinjing District, Shanghai,
      China. Patients with DME came from the local health network. OCT was performed in
      151 eyes of 100 type 2 diabetes patients with DR and 102 eyes of normal control
      subjects. Totally 795 cases were examined, and 215 of them were diagnosed to have
      DR. The average thickness of the macular fovea was 195.56 microm in 151 eyes from
      100 random samples. Forty-six eyes had macular thickening. The statistical
      analysis showed that there was a positive correlation between the thickness of
      the macular fovea and -log of best-corrected visual acuity (r = 0.2869, p =
      0.0004) as well as the severity of DR (p = 0.0003). However, there was no
      statistical significance between DME and posterior vitreous detachment. The
      images of OCT in DME included 3 types. Best-corrected visual acuity moderately
      correlated with retinal thickness. The macular thickness correlated with the
      severity of DR but not with posterior vitreous detachment.

PMID- 18097179
TI  - Effects of generated trans-arachidonic acids on retinal capillary during
      nitrative stress in diabetic rats.
AB  - PURPOSE: To investigate whether the trans-arachidonic acids (TAAs) change in
      diabetic conditions and the effect on capillary cells and its possible mechanism.
      METHODS: Diabetes was induced by intraperitoneal injection of streptozotocin at
      60 mg kg(-1) body weight. The amount of TAAs and arachidonic acid (AA) in serum
      of diabetic rats was measured by the gas chromatography and mass spectrometry
      method and the ratio of the peak area of TAAs to AA with a selected ion of 79 was
      estimated by group t test. The expression level of thrombospondin-1 (TSP-1) in
      the retina was examined by Western blot. The pericyte apoptotic index was
      investigated by flow cytometry. RESULT: The ratio of TAAs to AA significantly
      increased in serum at the time points of 8, 12 and 16 weeks after streptozotocin
      induction (p < 0.05). The expression of TSP-1 in the retina of diabetic rats
      elevated with longer duration of diabetes (checking the time points of 2-, 4-, 8
      , 12- and 16-week diabetic rats). The expression of TSP-1 tended to be
      physiologically elevated in relation to age but less significantly than in the
      diabetic group. TAAs could not induce the apoptosis of retinal pericytes (p >
      0.05). CONCLUSION: TAAs were generated associated with nitrative stress in
      diabetic rats and a possible mechanism of microvascular injury exits in diabetic
      conditions.

PMID- 18097180
TI  - Rat model for anterior segment intraocular surgery induced blood-retinal barrier
      breakdown.
AB  - PURPOSE: To develop a practical rat model of blood-retinal barrier (BRB)
      breakdown induced by anterior segment intraocular surgery. METHODS: A 27-gauge
      needle attached to infusion tubing running to a bottle of balanced salt solution
      was inserted through the limbus into the rat anterior chamber. The pressure of
      the balanced salt solution was oscillated from 0 to 12 mm Hg above the
      atmospheric pressure for 30 times. The needle was removed and the anterior
      chamber was formed. Then the eye was exposed vertically to the light of the
      operating microscope. The contralateral eye was left untreated. The eyes were
      applied with ofloxacin ophthalmic solution after surgery. At several time points
      after surgery, the integrity of the BRB was assessed by fluorescence fundus
      angiography, optical coherence tomography, immunohistochemical staining for serum
      albumin and quantitative measurement using Evans blue as a tracer. RESULTS: The
      extravasation of fluorescein, the increased central retinal thickness, strong
      staining for albumin in the retina and substantially elevated retinal Evans blue
      leakage demonstrated BRB breakdown after anterior segment intraocular surgery. On
      the 1st day after surgery, the model group showed a statistically significant
      elevation in the retinal Evans blue leakage as compared to the contralateral
      control group and the normal control group. These increased and reached the peak
      on the 2nd day after surgery and decreased to the point that there was no
      significant difference as compared to the contralateral control group and the
      normal control group on the 7th day after surgery. CONCLUSIONS: This study
      establishes a practical rat model of BRB breakdown induced by anterior segment
      intraocular surgery.

PMID- 18097181
TI  - Culture in vitro modulation of human leukocyte antigen molecules and
      costimulatory molecules on human retinal pigment epithelium.
AB  - PURPOSE: To determine the potential of culture in vitro to alter the human
      leukocyte antigen (HLA) molecules and costimulatory molecules on human retinal
      pigment epithelium (RPE). METHODS: Pure RPE were isolated and cultured. Two sets
      of RPE (normal and activated) were used. Activated RPE were obtained by
      incubating primary cultures of RPE with recombinant human interferon-gamma. The
      expression of HLA molecules and costimulatory molecules on human RPE at different
      passages after culture in vitro were analyzed quantitatively by flow cytometry.
      RESULTS: In the process of routine culture on culture flask, the duration of
      culture in vitro was significantly correlated with the expression of HLA-ABC
      molecules on the normal RPE and the activated RPE (r = -0.893, p < 0.001 and r = 
      0.964, p < 0.001 respectively), HLA-DR molecule on the activated RPE (r = -0.901,
      p < 0.001) and intercellular adhesion molecule-1 on the normal RPE (r = 0.961, p
      < 0.001). There were no correlations between the duration of culture in vitro and
      the expression of HLA-DR molecule on the normal RPE, intercellular adhesion
      molecule-1 on the activated RPE, B7-1 and B7-2 molecules on the normal RPE and
      the activated RPE. CONCLUSIONS: The chronic rejection is the major immunological
      rejection following RPE allogeneic graft. Culture in vitro modulation of HLA
      molecules and costimulatory molecules on RPE may increase lymphocyte infiltration
      and the activated RPE.

PMID- 18097182
TI  - Comparison of contrast sensitivity after angle-supported, iris-fixated and
      posterior chamber phakic intraocular lens implantation for high myopia.
AB  - PURPOSE: To evaluate the effects of angle-supported, iris-fixated and posterior
      chamber phakic intraocular lens (PIOL) implantation on contrast sensitivity (CS).
      METHODS: This prospective study included 69 eyes of 41 consecutive cases of high
      myopia which received an angle-supported (Phakic-6H; 26 eyes), iris-fixated
      (Verisyse; 23 eyes) or posterior chamber PIOL [phakic refractive lens (PRL); 20
      eyes]. Photopic, mesopic and mesopic with glare CS were evaluated preoperatively
      and at least 6 months postoperatively. RESULTS: In the PRL group, the mean
      postoperative CS at all frequencies and across all lighting conditions increased.
      These changes were significant for 6, 12 and 18 cycles per degree (cpd) under
      both photopic and mesopic conditions (p < 0.01) and for all the tested
      frequencies under mesopic with glare condition (p < or = 0.01). The average CS
      was relatively low in the PRL group. These changes were significant for 6 and 12
      cpd between the Verisyse and PRL group under photopic condition (p < 0.05), for 3
      and 6 cpd under mesopic condition (p < 0.01, p = 0.01) and under mesopic with
      glare condition (p < 0.01, p < 0.05). CONCLUSIONS: Improvements in postoperative
      CS confirm that PIOL implantation is a promising alternative for correction of
      high myopia. In comparison to posterior chamber PIOLs, angle-supported and iris
      fixated PIOLs seem to produce a better visual quality in terms of CS, which needs
      to be warranted by further investigations.

PMID- 18097183
TI  - Nerve growth factor helps protect retina in experimental retinal detachment.
AB  - PURPOSE: To investigate the expression of nerve growth factor (NGF) and its
      receptor TrkA on the retina at different time points after retinal detachment
      (RD) and the protection effect of NGF in experimental RD. METHODS: Sprague-Dawley
      rats were used as an RD animal model by injection of 0.1% sodium hyaluronate
      under the neurosensory retina. The expression of endogenous NGF and its receptor
      TrkA in the rat retina was detected using immunohistochemistry. The NGF (5
      mug/eye) or phosphate-buffered saline were injected separately into vitreous
      every 4 days after the RD. The rat eyes were then observed at various time
      points. Morphologic changes were investigated by light microscopy. Retinal
      gliosis was detected by glial fibrillary acidic protein labeling. RESULTS: The
      expression of endogenous NGF and TrkA was upregulated during RD procedure. Most
      of the NGF-treated retina had a well-organized structure. In NGF-treated RD eyes,
      the cells were still significantly more numerous than in phosphate-buffered
      saline-treated retina. Glial fibrillary acidic protein labeling increased quickly
      after RD; the NGF-treated retina had less reactive gliosis than the control
      groups. CONCLUSIONS: Intravitreal injection of exogenous NGF can protect retinal
      cells from degeneration in experimental RD. It may exert its protective action by
      preventing the apoptosis of retinal cells after RD.

PMID- 18097184
TI  - Congenital brain tumors in a series of seven patients.
AB  - BACKGROUND: Congenital brain tumors are very rare. We review these tumors in
      patients younger than 2 months diagnosed in our Department. METHODS: Seven
      congenital brain tumors were diagnosed during 5 years. Clinical and radiological
      findings and prognosis were analyzed. RESULTS: The study included 5 female and
      two male infants. Two cases were diagnosed antenatally by means of
      ultrasonography. All patients presented with intracranial hypertension. All
      neuroimaging studies revealed nonhomogenous tumors with cystic and solid
      components, except for the case with choroid plexus papilloma (CPP).
      Hydrocephalus was evident in all of them. Most were infratentorial lesions. There
      were three teratomas, one primitive neuroectodermal tumor, one ependymoblastoma
      and one CPP. Six patients were operated on, with one intraoperative death. Two
      passed away postoperatively with aspiration pneumonia. One patient died due to
      complications of chemotherapy and another one due to tumor recurrence 1 year
      after surgery. Only the patient with CPP is alive after 2 years. CONCLUSIONS:
      Today, the availability of noninvasive imaging procedures such as computerized
      tomography scan and magnetic resonance imaging has improved the diagnosis of
      congenital brain tumors. In spite of development in prenatal diagnosis,
      appropriate pre- and postoperative management, the mortality associated with
      these tumors still remains high. The final prognosis in these patients is still
      discouraging despite early surgery and operative and anesthetic improvements. CPP
      is accompanied by the best prognosis, whereas teratoma and primitive
      neuroectodermal tumors have the worst prognosis.

PMID- 18097185
TI  - Meningiomas in children.
AB  - OBJECTIVE: Pediatric meningioma is a rare diagnosis. This retrospective review
      seeks to elucidate pertinent characteristics of pediatric patients presenting
      with meningioma. METHODS: The Seattle Children's Hospital and Regional Medical
      Center brain tumor database was surveyed from 1940 through 2004. Twenty patients
      were identified. RESULTS: The median age of the 20 patients was 13 years. Five
      patients had radiation-induced meningiomas. Five patients had neurofibromatosis
      type 2. Ten patients had spontaneously arising meningiomas, 2 of which were
      malignant. CONCLUSION: Patients with spontaneously arising meningiomas were
      younger than those with identified risk factors. There was no recurrence in
      patients with radiation-induced meningiomas. The only death occurred in a patient
      with a malignant meningioma.

PMID- 18097186
TI  - Pediatric vertebral and spinal epidural tumors: a retrospective review of twelve
      cases.
AB  - OBJECTIVE: Pediatric vertebral tumors are rare, and most of the reported series
      have limited numbers of cases. Diagnosis of these tumors is difficult because of
      the patients' age and the rarity of the lesions. We aimed to report the clinical,
      radiological and pathological characteristics in a small series of pediatric
      vertebral and spinal epidural tumors and to discuss diagnostic and treatment
      difficulties. MATERIALS AND METHODS: Twelve consecutive pediatric cases with
      vertebral or spinal epidural tumors were reviewed retrospectively. RESULTS: The
      mean age was 12.6 years, and male and female patients were equal in number. The
      most common symptom was pain. There were some neurological or local findings in
      all patients, and there were some positive results on plain radiographs in all
      cases except 2. The tumors were removed totally in 9 cases. There were
      histologically malignant lesions in 3 and benign lesions in 9 cases. Three
      patients with malignant tumors were treated by radiotherapy and 2 by
      chemotherapy. One patient with thoracic hemangioma was also treated by
      embolization after surgery. One case with cervical Dabska's tumor died due to air
      embolization. The other patients were followed for 48.3 months. The preoperative
      neurological deficits were resolved completely in all patients except the one
      with only biopsy performed at the last follow-up. There were no new spinal
      deformities on follow-up. CONCLUSION: Children with vertebral tumors and spinal
      epidural tumors usually present with pain and neurological deficits or local
      findings, and there are some indications on plain radiographs. Therefore, a
      careful physical examination and detailed evaluation of radiographs may minimize
      the rate of misdiagnosis and underestimation. Most of these tumors are benign,
      therefore, their outcome is good, and cure may be possible for many of the cases.

PMID- 18097187
TI  - Protective effect of sildenafil (Viagra) in transient spinal cord ischemia.
AB  - Prospective study of the neuroprotective activity of sildenafil in a rat spinal
      ischemia model. The present study involved 21 male Sprague-Dawley rats. The
      animals were divided into 3 groups. Physiological serum was administered
      intraperitoneally to the 8 rats in the control group at the beginning of
      reperfusion for a period of 20 min after abdominal aortal occlusion. Sildenafil
      (Viagra) was administered as a single 10-mg/kg/day intraperitoneal dose to the 8
      rats in the sildenafil group at the beginning of reperfusion after 20 min of
      abdominal aortal occlusion. No occlusion was performed and no agent was
      administered to the 5 rats in the sham group, but the abdominal aorta was reached
      by means of surgical intervention. Before the animals were sacrificed, several
      physiological and biochemical parameters were investigated, preoperative and
      postoperative motor functions were also assessed, and somatosensory evoked
      potential (SEP) monitoring and histopathological examinations were carried out.
      No differences were found between the physiological and biochemical parameters in
      each of the 3 groups. Neurological scoring performed after reperfusion
      demonstrated a significant improvement in the neurological results relative to
      those of the control group over 48 h in subjects that received sildenafil. These
      animals also showed better 24-hour SEP results, measured in terms of extended
      latency and decreased amplitude, than the control animals. A histopathological
      study showed reduced ischemic symptoms in rats that received sildenafil compared
      with those in the control group. However, no anomalies were observed in the sham
      group with respect to the histopathological and neurological findings. These
      results indicate that neurological damage due to spinal-cord ischemia-reperfusion
      injury can be reduced by sildenafil.

PMID- 18097188
TI  - Delayed intrauterine repair of an experimental spina bifida with a collagen
      biomatrix.
AB  - BACKGROUND/PURPOSE: The aim of the study was to evaluate whether a collagen
      biomatrix is useful for delayed intrauterine coverage of a surgically created
      spina bifida in a fetal lamb. METHODS: In 20 fetal lambs, surgery was performed
      at 72 or 79 days' gestation. In 15 lambs a spina bifida was created surgically.
      In 8 lambs it was covered with a collagen biomatrix 2 weeks later and in 7 lambs
      it was left uncovered. Five lambs served as sham operated controls. Neurological
      examination was performed at 1 week of age and afterwards the lambs were
      sacrificed for further histological evaluation. RESULTS: None of the 5 surviving
      lambs with the defect covered showed loss of spinal function and the architecture
      of the spinal cord was preserved in 4 of the 5 lambs. In the uncovered group, 1
      of the 4 surviving lambs had loss of spinal function, 5 lambs were available for
      histological evaluation and 4 of them showed disturbance of the architecture of
      the spinal cord. CONCLUSIONS: Collagen biomatrices can be used for intrauterine
      coverage of an experimental spina bifida and can preserve the architecture of the
      spinal cord. Neurological outcome is not different between fetuses with their
      spinal cord covered and fetuses with uncovered cords.

PMID- 18097189
TI  - Treatment of cerebrospinal fluid shunting complications in a Nigerian
      neurosurgery programme. Case illustrations and review.
AB  - BACKGROUND/AIMS: For a century since the first cerebrospinal fluid (CSF) shunt
      surgery, ventriculoperitoneal (VP) shunt insertion for the treatment of
      hydrocephalus has routinely been performed. A lot of common and rare
      complications following this procedure have been reported in 24-47% of the cases.
      The aim of this paper was to present our experience with the treatment of
      hydrocephalus in our centre and highlight our management of two unusual
      complications with the available resources. METHODS: Retrospective clinical
      review. RESULTS: A total of 86 patients with hydrocephalus were seen in our unit.
      There were 52 males and 34 females (male:female ratio 3:2). The age of the
      patients ranged from 1 day to 68 years. The majority of the patients (92%) were
      below 5 years of age. Sixty-five patients had shunting procedures [VP shunt: 62
      (95.4%); endoscopic third ventriculostomy: 3 (4.6%)]. Of the 62 patients with VP
      shunts, 16 (25.8%) had complications while 2 of the 3 patients with endoscopic
      third ventriculostomies had complications. The complications following the VP
      shunts were CSF shunt sepsis (n = 12; 19.4%), abdominal complications (n = 3;
      4.8%), subdural haematoma (n = 2; 3.2%) and scalp necrosis in 1 patient.
      CONCLUSION: VP shunt procedures have come to stay and will remain with us despite
      recent advances such as endoscopic third ventriculostomy. Care should be taken to
      prevent all complications whether common or rare by paying particular attention
      to patient selection, shunt selection and surgical details. The adaptation of
      local technology and justified use of limited facilities and resources can go a
      long way in the management of both common and rare complications in developing
      nations.

PMID- 18097190
TI  - Pediatric intracranial meningiomas--do they differ from their counterparts in
      adults?
AB  - AIM: Meningiomas are very rare in children comprising only 0.44.1% of pediatric
      age tumors and only 1.5-1.8% of all intracranial neoplasms. We analyzed the
      clinical, pathological and management profile of these rare tumors and elucidated
      their differences from meningiomas in adults. METHODS: From 1990 to 2005, 33
      patients belonging to the pediatric age group with intracranial meningiomas were
      treated in NIMHANS. RESULTS: There were 19 male and 14 female children. The
      duration of symptoms ranged from 1 to 60 months. The study had a mean follow-up
      of 23.4 months. The commonest presenting symptoms were headache (90.9%) and
      visual disturbances (51.5%). Three patients had associated neurofibromatosis.
      Calcification was noticed in 22% of the tumors. Intraventricular meningiomas were
      the commonest (24.2%). Gross total or near total resection was possible in 22 out
      of 33 patients. Nine patients had reversible postoperative motor deficits.
      Fibrous meningioma was the commonest histological subtype (24.2%). Five patients
      had atypical or anaplastic subtypes. Adjuvant radiotherapy was administered in 4
      patients. Six patients had recurrences and underwent surgery. Ten patients
      required either staged procedures or multiple surgeries for the
      recurrence/residual tumors. CONCLUSION: Pediatric meningiomas are rare tumors and
      differ from those in adults by their male predominance, atypical locations,
      higher rates of malignant subtypes, recurrence and association with
      neurofibromatosis. Surgical management is challenging because of atypical
      location.

PMID- 18097191
TI  - Unusual ventriculoperitoneal shunt extrusion: experience with 5 cases and review
      of the literature.
AB  - Distal migration of ventriculoperitoneal shunt is rare. We present this unusual
      complication in 5 patients. The lower end of the shunt was extruded from right
      lumbar region, cervical area, umbilicus and rectum. The cause of such extrusion
      is not known. The patients were managed by shunt removal followed by shunt
      replacement on the opposite side.

PMID- 18097192
TI  - Transcortical approach to a huge pineal mature teratoma.
AB  - Intracranial teratomas are rare germ cell neoplasms occurring more often during
      childhood. We report the case of a huge mature teratoma of the pineal region in a
      10-year-old patient that was not correctly diagnosed preoperatively by
      stereotactic biopsy. The tumor was revealed by intracranial hypertension and a
      Parinaud syndrome. The tumor markers were within normal levels in the serum. A
      left transcortical parietal approach was used to completely resect the tumor. No
      adjuvant treatment was given. A complete neurological recovery was observed after
      the surgical procedure. Follow-up at 2 years did not show any recurrence. Pineal
      mature teratomas have a good prognosis, in contrast to their immature or mixed
      counterparts. A rigorous histological examination of the tumor samples is
      mandatory, in order to not omit a mixed contingent within the tumor. The
      treatment is exclusively surgical.

PMID- 18097193
TI  - Intramedullary cervical neurenteric cyst mimicking an abscess.
AB  - We describe a cervical intramedullary neurenteric cyst in a 12-year-old male
      patient who presented with gradual onset and progressively worsening neck pain,
      spastic quadriparesis and impaired sensation in the C(2) dermatome. MR imaging
      revealed a well-defined peripherally enhancing cystic intramedullary lesion with
      a posteroinferior enhancing nodule at the C(2)-C(3) level mimicking an abscess.
      There was no evidence of spinal dysraphism. The lesion was completely resected
      through a posterior approach and the patient showed radical improvement in his
      symptomatology. At follow-up after 3 years, he was asymptomatic and the MR
      imaging showed no evidence of any residual or recurrent cyst. The case presented
      here is unique, since a spinal neurenteric cyst showing intense peripheral
      contrast enhancement mimicking an abscess is unusual. The radiological features,
      pathogenesis and surgical considerations in cervical intramedullary neurenteric
      cysts are discussed and the relevant literature is briefly reviewed.

PMID- 18097194
TI  - Hydrothorax: transdiaphragmatic migration of a ventriculoperitoneal shunt
      catheter.
AB  - Symptomatic hydrothorax following ventriculoperitoneal shunt insertion is a very
      rare complication. The patient was a 5-month-old child known to have had shunted
      congenital hydrocephalus two months before. He presented to the emergency room in
      respiratory distress. Chest X-ray and computerized tomography images confirmed
      left hydrothorax and showed transdiaphragmatic migration of the tip of the
      peritoneal catheter to the thoracic cavity. After the catheter had been shortened
      and replaced to the peritoneal cavity, the patient's symptoms abated.

PMID- 18097195
TI  - Cerebrospinal fluid shunting in children on renal dialysis. Report of two cases.
AB  - The concurrent need for both cerebrospinal fluid shunting for hydrocephalus and
      dialysis for end-stage renal disease is rare. No large case series are found in
      the literature. Because dialysis involves frequent access to either the
      peritoneal cavity or the venous system, concern over potential cerebrospinal
      shunt infection represents a point of concern. We present 2 cases in which
      patients underwent both dialysis and cerebrospinal fluid shunting. In one case, a
      child underwent ventriculoperitoneal shunting, while in the second case
      ventriculoatrial shunting was performed as the initial procedure. Management
      strategies and potential complications are discussed.

PMID- 18097196
TI  - Hydrocephalus following bilateral jugular venous thrombosis in a child: case
      report and review of the literature.
AB  - Hydrocephalus resulting from bilateral thrombosis of the jugular veins has been
      rarely described in the literature. We report the case of an 18-month-old girl
      who was diagnosed with this condition following total parenteral nutrition. We
      also review the literature relevant to this subject and discuss the
      pathophysiology of hydrocephalus in the setting of bilateral jugular venous
      thrombosis.

PMID- 18097197
TI  - Prolonged cricopharyngeal muscle spasm after resection of the cervical vagus
      nerve in a 15-year-old.
AB  - Cervical vagal schwannomas are rare pediatric head and neck neoplasms that
      present a surgical challenge if the nerve is intimately involved with the mass.
      In some instances, resection of the vagus nerve with the mass is required. This
      will usually result in vocal cord paralysis and uncommonly dysphagia due to
      unilateral cricopharyngeal spasm. We present a case in which these two
      complications resulted in significant dysphagia and aspiration, which improved
      with expectant management.

PMID- 18097198
TI  - Natural progression of an unresected supratentorial ependymoma.
AB  - Ependymomas are rare gliomas that have been associated with a poor outcome
      despite aggressive therapy including surgery, chemotherapy and radiation therapy.
      We present a case report of a 16-year-old male with an untreated supratentorial
      ependymoma that lay dormant for 15 years without significant morbidity.
      Supratentorial ependymomas are thought to have a better outcome than
      infratentorial ependymomas, primarily because of the increased likelihood of
      achieving a gross total resection in the supratentorial space. Our case report
      suggests that the improved outcome may be due in part to the biologically benign
      nature of some supratentorial ependymomas. This highly unusual case illustrates
      the unpredictable heterogeneity of pediatric ependymomas.

PMID- 18097199
TI  - Clear cell ependymoma of the temporal lobe in a child: a case report.
AB  - A 12-year-old boy with a left temporal tumor diagnosed as clear cell ependymoma
      (CCE) was reported. CCE is an uncommon central variant of ependymomas with a
      predilection for the supratentorial region in children. Brain tumors with a
      honeycomb pattern with clear cells having round nuclei and perinuclear halos
      could pose a problem in the differential diagnosis with the other tumors with
      clear cells. There were 41 reported cases of CCE in the literature. In 61% of
      these cases, tumors were located in the supratentorial region, and in the others
      in the posterior fossa and spinal cord. However, there was none located in the
      temporal lobe except in the case presented here.

PMID- 18097200
TI  - A case of diastematomyelia associated with hamartoma masquerading as meningocele
      in the newborn infant.

PMID- 18097201
TI  - 'Armoured brain'. A case report of a calcified chronic subdural haematoma.

PMID- 18097202
TI  - Re: A witnessed short fall mimicking presumed shaken baby syndrome (inflicted
      childhood neurotrauma).

PMID- 18097203
TI  - Neonatal nursing and China.

PMID- 18097204
TI  - Prone sleeping and preterm infants.

PMID- 18097205
TI  - So many alarms, so much noise.

PMID- 18097206
TI  - Hearing screening and sudden infant death syndrome.

PMID- 18097207
TI  - Family centered care map has a new home.

PMID- 18097208
TI  - Codeine not safe for some breastfed infants.

PMID- 18097209
TI  - Perinatal perimortem and postmortem examination: obligations and considerations
      for perinatal, neonatal, and pediatric clinicians.
AB  - Clinicians are called upon to participate in a variety of clinical scenarios in
      which babies will die. A number of factors have caused the most appropriate
      method of evaluating cause(s) of death, namely autopsy, to fall to record low
      numbers during the past decade. Because of obligations unique to the stillborn
      fetus, dead or dying infant or child, and family and siblings, it is important
      for clinicians to understand the importance and utility of postmortem
      examination. Postmortem examination is of multidisciplinary importance to
      determine the cause of death and contributing and related diagnoses. This article
      summarizes some of what is known about postmortem examination and provides a list
      of guidelines available on the Internet and in the medical literature for the
      systematic assessment of perinatal death and the provision of appropriate
      testing. Clinicians are encouraged to use their leadership roles to improve rates
      of postmortem examination and to participate in research and education to improve
      its occurrence.

PMID- 18097210
TI  - Epidermolysis bullosa: a case study in transport, treatment, and care.
AB  - There are skin rashes, lesions, and disorders in the neonatal period that require
      emergent assessment and consultation. A neonate presented with epidermolysis
      bullosa and provided an opportunity for learning about this condition and various
      dermatologic resources, primarily DermAtlas. The neonate with suspected
      epidermolysis bullosa that is delivered in a community setting usually requires
      transport to a neonatal intensive care unit with pediatric subspecialty care. A
      case study involving the transport of a neonate with this condition is reviewed,
      followed by a discussion of the etiology, incidence, pathogenesis, diagnosis, and
      nursing care before and during transport and parental considerations. The
      resources available in the neonatal community, primarily DermAtlas, for the
      identification of epidermolysis bullosa and other dermatological conditions is
      explored.

PMID- 18097211
TI  - Trivalent inactivated influenza vaccine compliance rate in neonatal intensive
      care unit parents.
AB  - The American Academy of Pediatrics (AAP) recommends injected, inactivated
      influenza vaccine for all close contacts of high-risk infants. This population
      includes parents of infants younger than 59 months of age, with an emphasis on
      children 0-6 months who are not direct candidates for immunization. This 0-6
      month age group is a major component of the neonatal intensive care unit (NICU)
      population. No data exist on the compliance rate with influenza vaccine in this
      specific parent population. The purpose of this study was to assess the
      compliance rate among this parent population and compare it with vaccine use in
      the general adult population at the time, which has traditionally ranged from 25%
      to 32%. The study also sought reasons for poor compliance with flu vaccine.
      Answering this question is important in determining whether programs directly
      aimed at NICU parents are required to achieve compliance or if simply informing
      parents of the need to be immunized results in sufficient vaccination rates. For
      14 weeks during the 2004-2005 influenza season, 92 randomly selected parents
      (from 56 inborn infants) underwent an informational program regarding influenza
      vaccine and the risks and benefits of vaccination. Parents were surveyed in the
      spring to assess if they obtained the injection the previous winter. Subjects
      were parents of NICU patients admitted to the New York University NICU during the
      14-week study period. The main outcome measure was the influenza vaccination rate
      of the parental cohort that underwent the informational program. For those who
      intended to receive influenza vaccination but did not, reasons for noncompliance
      were assessed via standardized telephone interview. After the information
      session, 85 parents (92%) indicated they intended to obtain the vaccine; however
      30 parents (32.6%) actually received it by the following spring. The most
      commonly cited reason for failing to obtain influenza vaccine was convenience. No
      correlation between parents who obtained the vaccine and infant birth weight,
      gestational age, or length of stay was observed. Compliance with national
      recommendations to obtain trivalent inactivated influenza vaccine in this highly
      specified parent population is roughly equivalent to the national average of all
      adults in the general population. Caregivers of high-risk neonates must
      encourage/offer immunization to this targeted population.

PMID- 18097212
TI  - A summary of NICU fat emulsion medication errors and nursing services: data from
      MEDMARX.
AB  - Intralipid infusions remain a critical part of ensuring adequate nutritional
      supplement and growth in premature and term infants. Managing intralipid therapy
      requires great care to prevent metabolic and physiological side effects. The
      authors sought to systematically study medication errors associated with
      intralipid administration in the neonatal intensive care unit (NICU). A
      descriptive quantitative and qualitative analysis incorporating secondary data
      was used. Medication error data were drawn from 54 institutions that voluntarily
      participated with MEDMARX, a national, Internet-accessible medication error
      reporting program owned and operated by the United States Pharmacopeia. These
      errors were associated with NICUs, and each medication error record identified
      nursing staff as making the initial error. A total of 257 errors were reviewed,
      with 3.9% resulting in harm. The mean age of the neonate was 7 days, and more
      errors occurred on Mondays than any other day of the week. Errors
      disproportionately occurred between 6 pm and midnight, with a significant
      difference between errors near 7 am and 7 pm (P = .002). Wrong dose errors
      occurred in 69% of the sample. Nearly one quarter of the errors resulted from
      misprogramming infusion devices (either pumps or syringes). Qualitative findings
      revealed that many of the errors were the result of the nurse's misinterpretation
      of the modes (ie, time, volume, or rate) on the infusion device or by not
      recognizing the decimal point on the device's display panel. Several errors
      involved switching the rate of infusion with total parenteral nutrition and that
      of intralipids. Voluntary medication error reporting offers valuable insights
      into intralipid errors occurring in NICUs. Secondary analysis is an ethical,
      economic means of studying the occurrence of such errors. MEDMARX data suggest
      that some of the serious errors are the result of complex care and equipment
      needed for these vulnerable infants.

PMID- 18097214
TI  - Guidelines for bottle feeding your premature baby.
AB  - Prolonged use of gavage feedings is common in premature infants who have not yet
      acquired suck, swallow, and breathing coordination. Preterm infants must be
      developmentally mature to orally feed successfully. Als' Synactive Theory of
      Development offers a conceptual framework to facilitate understanding of how
      premature infants dynamically differentiate to attain developmental milestones
      such as oral feeding. Key clinical implications for neonatal nurses are
      contingent upon incorporating evidence-based research into practice and providing
      consistent quality care to improve feeding outcomes.

PMID- 18097215
TI  - A parent's guide to bottle feeding your premature baby.
AB  - Bottle feeding ... what an exciting time for you and your baby! This teaching
      guide gives helpful tips for feeding.

PMID- 18097216
TI  - Stress in fathers of surgical neonatal intensive care unit babies.
AB  - The purpose of this study was to identify and measure components of perceived
      stress in fathers of infants in a surgical neonatal intensive care unit (NICU).
      The Parent Stressor Scale: Infant Hospitalization (PSS:IH) was used to assess
      perceived stress in 22 fathers. Paternal stress was highest in the domains of
      "Parental Role Alteration" and "Infant Appearance and Behavior." "Sights and
      Sounds" did not appear to be associated with self-reported stress. This study
      demonstrates elevated levels of perceived stress among fathers of surgical NICU
      babies. Attention to fathers may be assisted by findings.

PMID- 18097217
TI  - Neonatal advanced practice nurses shift length, fatigue, and impact on patient
      safety.

PMID- 18097218
TI  - Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides
      for maintenance therapy of HIV.
AB  - BACKGROUND: Prior attempts to reduce the number of drugs needed to maintain viral
      suppression in patients with suppressed HIV replication while receiving three
      antiretroviral drugs have been unsuccessful. METHODS: In 205 patients with
      suppressed HIV replication on lopinavir-ritonavir and two nucleosides, this
      randomized, open-label, non-inferiority clinical trial compared the strategies of
      continuation of triple therapy versus lopinavir-ritonavir monotherapy followed by
      reinduction with two nucleosides if virological rebound occurred without
      genotypic resistance to lopinavir-ritonavir. The primary endpoint was proportion
      of patients without therapeutic failure, defined as confirmed HIV RNA higher than
      500 copies/mL (with exclusion of patients receiving monotherapy who resuppressed
      to < 50 copies/mL after resuming baseline nucleosides), or loss to follow-up, or
      change of randomized therapy other than reinduction. RESULTS: At week 48, the
      percentage of patients without therapeutic failure was 94% in the monotherapy
      group versus 90% in the triple therapy group (difference,-4%; upper limit of 95%
      confidence interval for difference, 3.4%). The percentage of patients with HIV
      RNA 50 copies/mL at 48 weeks by intention-to-treat, missing data or reinductions
      considered as failures, were 85% in the monotherapy group versus 90% in the
      triple therapy group (P = 0.31; 95% upper limit of 95% confidence interval for
      difference, 14%). CONCLUSION: In this trial, 48 weeks of lopinavir-ritonavir
      monotherapy with reintroduction of nucleosides as needed was non-inferior to
      continuation of two nucleosides and lopinavir-ritonavir in patients with prior
      stable suppression. However, episodes of low level viremia were more common in
      patients receiving monotherapy.

PMID- 18097219
TI  - The role of the thymus in HIV infection: a 10 year perspective.

PMID- 18097220
TI  - CCR5 or CXCR4 use influences the relationship between CD4 cell depletion, NKp44L
      expression and NK cytotoxicity in SHIV-infected macaques.
AB  - OBJECTIVE: HIV-1 infection is characterized by a progressive decline of CD4 cell
      count, the underlying mechanisms of which are still debated. We recently found
      that during HIV-1 infection, CD4 T cells overexpress a ligand of the NK
      activating receptor NKp44 (NKp44L) and are sensitized to NK cytolytic activity.
      The expression of NKp44L is triggered by a highly conserved motif of gp41 (3S)
      and is inhibited by anti-3S antibodies. DESIGN: To assess whether viral tropism
      can affect NKp44L expression, NK cytotoxicity, and anti-3S antibodies production,
      10 macaques were infected either with the CCR5 tropic SHIV162P3 or with a
      CXCR4/CCR5 dual-tropic SHIV89.6P. RESULTS: In SHIV162P3-infected macaques,
      expression of NKp44L was inversely correlated with anti-3S antibodies, in
      relation to CD4 depletion and NK cytotoxicity. By contrast, no such correlation
      was found in macaques infected with SHIV89.6P which, induced a rapid decline of
      CD4 T cells. CONCLUSIONS: These results highlight the key role played by NK cells
      in CD4 cell count decline with respect to coreceptor usage, and provided the
      setting to investigate new strategies for preventive and/or therapeutic
      immunization to stimulate anti-3S antibodies.

PMID- 18097221
TI  - Maternal Herpes simplex virus type 2 infection, syphilis and risk of intra-partum
      transmission of HIV-1: results of a case control study.
AB  - BACKGROUND: Genital ulcer disease including that caused by Herpes simplex virus
      type 2 (HSV-2) and syphilis facilitates sexual transmission of HIV-1. The effect
      of these infections on intra-partum mother-to-child-transmission (MTCT) of HIV-1
      is unknown. METHODS: A case-control study was conducted using archived sera from
      HIV-1 positive women enrolled in ZVITAMBO, an MTCT trial. Cases were 509 women
      who transmitted HIV-1 to their infants intra-partum; controls were 1018 women
      whose infants remained uninfected at 12 months. Maternal serum collected at
      delivery, were tested for HSV-2 antibody. The 6-week post-partum sample was also
      tested for syphilis by RPR and TPHA to identify women with incubating or active
      syphilis at delivery. Rates of prevalent and incident HSV-2 and recently acquired
      syphilis were compared between cases and controls. FINDINGS: Overall prevalence
      of maternal HSV-2 and active syphilis at delivery were 82.5% [95% confidence
      interval (CI), 80.6-84.5] and 4.0% (95% CI, 3.0-5.1), respectively. Prevalent HSV
      2 was associated with increased intra-partum MTCT [adjusted odds ratio (OR),
      1.50; 95% CI, 1.09-2.08]. The proportion of intra-partum transmissions
      potentially attributable to prevalent HSV-2 infection was 28.4% (95% CI, 7.3
      44.7). Maternal infection with active syphilis at delivery was not associated
      with intra-partum MTCT (unadjusted OR, 0.89; 95%CI, 0.49-1.59; adjusted OR, 0.64;
      95% CI, 0.34-1.20). INTERPRETATION: HSV-2 infection is common among HIV-1
      positive women and is associated with an increased risk of intra-partum MTCT.
      More than 25% of intra-partum MTCT may be attributable to maternal HSV-2 co
      infection. Active maternal syphilis at the time of delivery is not associated
      with intra-partum MTCT risk.

PMID- 18097222
TI  - Intrahepatic mRNA expression in hepatitis C virus and HIV/hepatitis C virus co
      infection: infiltrating cells, cytokines, and influence of HAART.
AB  - OBJECTIVE: Liver disease is more progressive in HIV/hepatitis C virus (HCV) co
      infection than in HCV infection alone. This accelerated pathogenesis is probably
      influenced by differences in the composition of infiltrating inflammatory cells
      and the local release of inflammatory and profibrogenic cytokines. METHODS: Using
      quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR)
      we studied intrahepatic messenger RNA levels of cytokines and cellular markers
      defining distinct subsets of inflammatory cells in liver biopsies from 33 HCV
      mono-infected and 40 HIV/HCV-co-infected patients. RESULTS: Despite their well
      preserved peripheral blood CD4 cell counts (median 598 cells/microl), HIV/HCV-co
      infected patients displayed significantly lower CD4 mRNA levels than HCV-mono
      infected patients, whereas increased mRNA levels of CD3epsilon, TCRalpha,
      CD8alpha and CD8beta suggested intrahepatic enrichment of CD8 T cells in HIV co
      infection. Intrahepatic mRNA levels of the inflammatory cytokines interferon
      gamma (IFN-gamma), regulated upon activation, normal T-cell expressed and
      secreted (RANTES, CCL5), macrophage inflammatory protein 1 alpha (CCL3) and
      interferon-inducible protein 10 (CXCL10) were significantly higher in HIV
      positive than in HIV-negative patients, whereas mRNA levels of the profibrogenic
      cytokines macrophage chemoattractant protein 1 (CCL2), secondary lymphochemokine
      (CCL21) and stroma-derived factor 1 (CXCL12) did not differ between the two
      groups. All changes were less pronounced in the subgroup of HIV-positive patients
      receiving antiretroviral treatment (HAART) than in untreated HIV-positive
      patients. CONCLUSION: The accelerated liver disease observed in HIV/HCV-co
      infected patients might reflect enhanced intrahepatic inflammatory responses
      rather than increased local transcription of directly profibrogenic cytokines.

PMID- 18097223
TI  - Differences in proviral DNA load between HIV-1- and HIV-2-infected patients.
AB  - INTRODUCTION: The lesser pathogenicity of HIV-2 relative to HIV-1 is generally
      attributed to its slower replication. To compare the amounts of total HIV DNA
      during human HIV-1 and HIV-2 infection, we developed a quantitative real-time PCR
      method with a unique external quantification standard based on a single plasmid
      harboring both the HIV-1 and the HIV-2 LTR. METHODS: Viral DNA load was compared
      between 40 HIV-1-infected and 42 HIV-2-infected antiretroviral-naive patients.
      RESULTS: The difference between HIV-1 and HIV-2 proviral DNA load was highly
      significant in patients with CD4 cell counts > 500 cells/microl [HIV-1: n = 14;
      median, 2.5; interquartile range (IQR), 2.1-2.7; HIV-2: n = 22, median, 1.6; IQR,
      1.0-2.0] and in patients with CD4 cell counts between 300 cells/microl and 500
      cells/microl (HIV-1: n = 12; median, 2.7; IQR, 2.3-2.8; HIV-2: n = 11; median,
      2.0; IQR, 1.0-2.4). Too few HIV-2-infected patients had CD4 cell counts < 300
      cells/microl to detect a significant difference but DNA values were again lower
      in HIV-2-infected patients (HIV-1: n = 14; median, 2.9; IQR, 2.2-3.2; HIV-2: n =
      9; median, 2.7; IQR, 2.2-3.3). CONCLUSIONS: These differences are in line with
      the natural histories of the two infections and show that HIV-2 infection is a
      valid model for studying the pathophysiology of HIV infection in general.

PMID- 18097224
TI  - NKG2C is a major triggering receptor involved in the V[delta]1 T cell-mediated
      cytotoxicity against HIV-infected CD4 T cells.
AB  - BACKGROUND: Gammadelta T cells share with natural killer (NK) cells many effector
      capabilities and cell-surface proteins, including the NKG2 receptor family. A
      subset of gammadelta T cells that express the variable Vdelta1 region plays a
      critical role in immune regulation, tumour surveillance and viral infection.
      Dramatic expansion of Vdelta1 T cells has been observed in HIV disease.
      OBJECTIVE: To determine if NKG2C expression on Vdelta1 T cells during HIV-1
      infection is correlated with CD4 cell count and involved in lysis of CD4 T cells.
      METHODS: gammadelta T cells from viraemic HIV-infected patients were examined.
      Expression of NK cell markers was analyzed by flow cytometry. The cytolytic
      activity of Vdelta1 T cells was determined by either Cr-release assays or
      degranulation assays against HLA-E-transfected 721.221 cells or HIV-infected CD4
      primary T cells. RESULTS: The expression of C-type lectin NKG2 receptors was
      sharply modulated on gammadelta T cells in patients with HIV infection. A
      profound decrease of Vdelta1 T cells bearing inhibitory NKG2A receptors
      corresponded to a drastic expansion of a distinct population of Vdelta1 T cells
      expressing a functional activating NKG2C receptor. Engagement of HLA-E, the
      ligand of both NKG2A and NKG2C, which is specifically induced on HIV-infected CD4
      T cells, substantially enhanced the Vdelta1 T cell-mediated cytotoxicity.
      CONCLUSIONS: These results raise the possibility that induction of NKG2C
      expression on Vdelta1 T cells plays a key role in the destruction of HIV-infected
      CD4 T cells during HIV disease.

PMID- 18097225
TI  - Zidovudine/lamivudine contributes to insulin resistance within 3 months of
      starting combination antiretroviral therapy.
AB  - BACKGROUND: Patients with antiretroviral therapy (ART)-associated lipodystrophy
      frequently have disturbances in glucose metabolism associated with insulin
      resistance. It is not known whether changes in body composition are necessary for
      the development of these disturbances in ART-naive patients starting treatment
      with different combination ART regimens. METHODS: Glucose metabolism and body
      composition were assessed before and after 3 months of ART in a prospective
      randomized clinical trial of HIV-1-positive ART-naive men taking
      lopinavir/ritonavir within either a nucleoside reverse transcriptase inhibitor
      (NRTI)-containing regimen (zidovudine/lamivudine; n = 11) or a NRTI-sparing
      regimen (nevirapine; n = 9). Glucose disposal, glucose production and lipolysis
      were measured after an overnight fast and during a hyperinsulinaemic-euglycaemic
      clamp using stable isotopes. Body composition was assessed by computed tomography
      and dual-energy X-ray absorptiometry. RESULTS: In the NRTI-containing group, body
      composition did not change significantly in 3 months; insulin-mediated glucose
      disposal decreased significantly (25%; P < 0.001); and fasting glycerol turnover
      increased (22%; P < 0.005). Hyperinsulinaemia suppressed glycerol turnover
      equally before and after treatment. The disturbances in glucose metabolism were
      not accompanied by changes in adiponectin or other glucoregulatory hormones. In
      contrast, glucose metabolism did not change in the NRTI-sparing arm. Glucose
      disposal significantly differed over time between the arms (P < 0.01).
      CONCLUSIONS: Treatment for 3 months with a NRTI-containing, but not a NRTI
      sparing, regimen resulted in a 25% decrease in insulin-mediated glucose disposal
      and a 22% increase in fasting lipolysis. In the absence of discernable changes in
      body composition, NRTI may directly affect glucose metabolism, the mechanism by
      which remains to be elucidated.

PMID- 18097226
TI  - Fixed duration interruptions are inferior to continuous treatment in African
      adults starting therapy with CD4 cell counts < 200 cells/microl.
AB  - BACKGROUND: Structured treatment interruption (STI) of antiretroviral therapy
      (ART) could potentially reduce cost and toxicity, but clinical efficacy requires
      evaluation. METHODS: An assessment of fixed-duration STI was nested in DART, a
      multicentre trial comparing strategies for monitoring ART in Uganda and Zimbabwe
      (ISCRTN 13968779). Of 3316 ART-naive symptomatic adults with CD4 cell count < 200
      cells/microl at ART initiation, 813 with > or = 300 cells/microl after 48 or 72
      weeks underwent a second randomization to either STI, cycles of 12 weeks on/off
      (408), or continuous ART (CT; 405). RESULTS: Median age at STI/CT randomization
      was 37 years (range, 19-67) and CD4 cell count 358 cells/microl (range, 300
      1054). A second review terminated the STI/CT randomisation on 15 March 2006, and
      participants changed to CT. Median follow-up was 51 weeks (range, 0-85): 99% and
      50% of time was spent on ART in CT and STI, respectively. First new World Health
      Organization (WHO) stage 4 events or death occurred more frequently in STI (24;
      6.4/100 person-years) than CT (9; 2.4/100 person-years) (hazard ratio, 2.73; 95%
      confidence interval, 1.27-5.88; P = 0.007); oesophageal candidiasis being the
      most frequent event (STI, 13; CT, 3). Nine (1%) participants died (STI, 5; CT,
      4). There was no difference in time to first serious adverse event (P = 0.78),
      although ART change owing to toxicity occurred more with CT (10; 2.6/100 person
      years) than with STI (2; 0.5/100 person-years) (P = 0.02). CONCLUSIONS: Although
      absolute rates of WHO stage 4 events/death were low, 12 week STIS initiated at a
      CD4 cell count >/= 300 cells/microl resulted in a greater than twofold increased
      relative rate of disease progression compared with continuous therapy in adult
      Africans initiating ART with advanced disease, and cannot be recommended.

PMID- 18097227
TI  - Pharmacokinetics, safety and efficacy of lopinavir/ritonavir in infants less than
      6 months of age: 24 week results.
AB  - OBJECTIVE: To investigate pharmacokinetics, safety and efficacy of
      lopinavir/ritonavir (LPV/r)-based therapy in HIV-1-infected infants 6 weeks to 6
      months of age. METHODS: A prospective, multicenter, open-label trial of 21
      infants with HIV-1 RNA > 10 000 copies/ml and treated with LPV/r 300/75 mg/m
      twice daily plus two nucleoside reverse transcriptase inhibitors. Intensive
      pharmacokinetic sampling was performed at 2 weeks and predose concentrations were
      collected every 8 weeks; safety and plasma HIV-1 RNA were monitored every 4-12
      weeks for 24 weeks. RESULTS: Median age at enrollment was 14.7 weeks (range, 6.9
      25.7) and 19/21 completed > or= 24 weeks of study. Although LPV/r apparent
      clearance was slightly higher than in older children, the median area under the
      concentration-time curve 0-12 h (67.5 mug.h/ml) was in the range reported from
      older children taking the recommended dose of 230/57.5 mg/m. Predose
      concentrations stabilized at a higher level after the first 2 weeks of study. In
      as-treated analysis at week 24, 10/19 (53%) had plasma HIV-1 RNA < 400 copies/ml
      (median change, -3.33 log10 copies/ml); poor adherence contributed to delayed
      viral suppression, which improved with longer follow-up. Three infants (14%) had
      transient adverse events of grade 3 or more that were possibly related to study
      treatment but did not require permanent treatment discontinuation. CONCLUSION:
      Despite higher clearance in infants 6 weeks to 6 months of age, a twice daily
      dose of 300/75 mg/m LPV/r provided similar exposure to that in older children,
      was well tolerated and provided favorable virological and clinical efficacy.

PMID- 18097229
TI  - Can response of a pruritic papular eruption to antiretroviral therapy be used as
      a clinical parameter to monitor virological outcome?
AB  - BACKGROUND: A pruritic papular eruption (PPE) is a common skin manifestation
      observed in 12-46% of persons with HIV infection living in tropical countries.
      OBJECTIVE: To determine whether PPE responds to HAART and whether monitoring PPE
      severity could be used as a clinical marker to predict virological outcome in
      resource-limited settings where viral load testing is not available. METHODS: The
      study enrolled 53 patients with PPE for at least 1 month before starting a first
      line HAART regimen as part of a prospective study. CD4 cell count and viral load
      were measured at enrolment and every 3 months. A scoring system was developed to
      evaluate the PPE severity by asking two questions. Over the last month how itchy
      has your skin been? Over the last month how has itching interfered with your
      sleep? RESULTS: Median CD4 cell count was 15 cells/mul and median viral load 268
      663 copies/ml. All patients initiated a regimen containing a nonnucleoside
      reverse transcriptase inhibitor. Mean PPE score declined from 3.9 at enrolment to
      0.1 at 24 months. In 37 (86%) of the 43 patients with at least 6 months of follow
      up data, the PPE disappeared and never returned. Patients with viral load > 400
      copies/ml at months 9 and/or 12 had significantly higher PPE scores at months 9
      to 12 than the patients with < 400 copies/ml. CONCLUSIONS: In most patients, PPE
      disappears during HAART and PPE severity scores were higher in patients whose
      first-line HAART failed to control plasma viral load.

PMID- 18097228
TI  - Asymptomatic myocardial ischaemia in HIV-infected adults.
AB  - BACKGROUND: Asymptomatic ischaemic heart disease (IHD) in HIV-infected patients
      has not been studied. METHODS: Resting, 12-lead electrocardiograms (ECG) were
      evaluated for asymptomatic IHD (Q-wave and/or ST segment depression) at baseline
      from HIV-infected participants with no known IHD enrolling in the SMART study.
      The ECG recordings were standardized and centrally analysed. Factors associated
      with asymptomatic IHD were identified by logistic regression, sequentially
      adjusted for demographics, clinical history, metabolic risk factors and type and
      duration of antiretroviral therapy (ART). RESULTS: Of 4831 participants with an
      evaluable, baseline ECG and no prior IHD, mean age was 44 years (SD, 9.3); 28.4%
      were female; 6.6% had diabetes; 16.5% were receiving antihypertensive therapy;
      and 95.4% were ART experienced. ECG evidence of IHD was detected in 526 (10.9%)
      [Q-wave in 283 (5.9%), ST segment depression in 264 (5.5%)]; 16.7% in those 60
      years or older. Variables independently associated with these abnormalities were
      older age [age > or= 60 versus < 40 years: odds ratio (OR), 2.2; 95% confidence
      interval (CI), 1.5-3.2; P < 0.001], current antihypertensive therapy (OR, 1.5;
      95% CI, 1.1-1.9; P = 0.003) and recruitment in Europe (OR, 1.4; 95% CI, 1.1-1.7;
      P = 0.004) or Asia (OR, 1.6; 95% CI, 1.0-2.6; P = 0.05), both compared with North
      America. Diabetes was borderline significant (OR, 1.4; 95% CI, 1.0-2.0; P =
      0.06). CONCLUSIONS: ECG evidence of asymptomatic IHD was common in this large
      cohort of HIV-infected adults and more common than a history of symptomatic IHD.
      Traditional factors were the predominant determinants of risk. No clear
      association between ART type or duration and asymptomatic IHD was noted.

PMID- 18097231
TI  - Population prevalence of reported and unreported HIV and related behaviors among
      the household adult population in New York City, 2004.
AB  - BACKGROUND: Surveillance for HIV likely underestimates infection among the
      general population: 25% of US residents are estimated to be unaware of their HIV
      infection. OBJECTIVE: To determine the prevalence of HIV infection and risk
      behaviors among New York City (NYC) adults and compare these with surveillance
      findings. METHODS: The NYC Health and Nutrition Examination Survey (HANES)
      provided the first opportunity to estimate population-based HIV prevalence among
      NYC adults. It was conducted in 2004 among a representative sample of adults > 20
      years. Previously reported HIV infection was identified from the NYC HIV/AIDS
      Surveillance Registry. A blinded HIV serosurvey was conducted on archived blood
      samples of 1626 NYC HANES participants. Data were used to estimate prevalence for
      HIV infection, unreported infections, high-risk activities, and self-perceived
      risk. RESULTS: Overall, 18.1% engaged in one or more risky sexual/needle-use
      behaviors, of which 92.2% considered themselves at low or no risk of HIV or
      another sexually transmitted disease. HIV occurred in 21 individuals (prevalence
      1.4%; 95% confidence interval (CI), 0.8-2.5]; one infection (5%; 95% CI, 0.7
      29.9) was not reported previously and possibly undiagnosed. HIV infection was
      significantly elevated in those with herpes simplex virus 2 (4%), men who have
      sex with men (14%), and needle-users (21%) (P < 0.01). CONCLUSIONS: Among NYC
      adults, HIV prevalence was consistent with surveillance findings overall. The
      proportion of unreported HIV was less than estimated nationally, but findings
      were limited by sample size. Most adults with risky behaviors perceived
      themselves to be at minimal risk, highlighting the need for risk reduction and
      routine HIV screening.

PMID- 18097230
TI  - Efficacy and tolerability of long-term efavirenz plus nucleoside reverse
      transcriptase inhibitors for HIV-1 infection.
AB  - OBJECTIVE: To compare the long-term efficacy and tolerability of two efavirenz
      containing regimens with those of an indinavir-containing regimen in the initial
      use of HAART. METHOD: HIV-1-infected patients (N = 1266) were randomly assigned
      to receive one of three regimens: efavirenz, zidovudine plus lamivudine, n = 422;
      efavirenz plus indinavir, n = 429; or indinavir, zidovudine plus lamivudine, n =
      415. Entrance criteria included baseline viral load greater than 10 000 copies/ml
      HIV-1 RNA, CD4 cell count 50 cells/mul or greater, and no previous use of
      lamivudine, any non-nucleoside reverse-transcriptase inhibitor or protease
      inhibitor. The primary endpoint was the proportion of patients (response rate) in
      each regimen with a viral load under 400 copies/ml at 168 weeks of treatment.
      RESULTS: Response rates at 168 weeks were 30% in the indinavir, zidovudine,
      lamivudine group, 48% in the efavirenz, zidovudine, lamivudine group (P < 0.0001,
      difference estimate; 97.5% confidence interval (CI) 18.5; 10.9, 26), and 40% in
      the efavirenz plus indinavir group (P = 0.0018, difference estimate; 97.5% CI
      10.2; 2.9, 17.6). Median CD4 cell counts increased above respective baselines by
      292 cells/mul (efavirenz, zidovudine, lamivudine and indinavir, zidovudine,
      lamivudine) and 300 cells/mul (efavirenz plus indinavir). Total discontinuations
      were 54% (efavirenz, zidovudine, lamivudine), 63% (efavirenz plus indinavir), and
      69% (indinavir, zidovudine, lamivudine) of which 13, 12 and 26%, respectively,
      were caused by adverse events. No new or unexpected increases in the rates or
      severity of adverse events occurred from long-term treatment with efavirenz
      containing regimens. CONCLUSION: Long-term HIV therapy with efavirenz-containing
      regimens, particularly efavirenz, zidovudine, lamivudine, provides significantly
      greater antiviral activity and tolerability than a regimen of indinavir,
      zidovudine plus lamivudine.

PMID- 18097232
TI  - Mother-to-child HIV transmission despite antiretroviral therapy in the ANRS
      French Perinatal Cohort.
AB  - OBJECTIVE: To identify factors associated with mother-to-child HIV-1 transmission
      (MTCT) from mothers receiving antenatal antiretroviral therapy. DESIGN: The
      French Perinatal Cohort (EPF), a multicenter prospective cohort of HIV-infected
      pregnant women and their children. METHODS: Univariate analysis and logistic
      regression, with child HIV status as dependent variable, were conducted among
      5271 mothers who received antiretroviral therapy during pregnancy, delivered
      between 1997 and 2004 and did not breastfeed. RESULTS: The MTCT rate was 1.3%
      [67/5271; 95% confidence interval (CI), 1.0-1.6]. It was as low as 0.4% (5/1338;
      95% CI, 0.1-0.9) in term births with maternal HIV-1 RNA level at delivery below
      50 copies/ml. MTCT increased with viral load, short duration of antiretroviral
      therapy, female gender and severe premature delivery: 6.6% before 33 weeks versus
      1.2% at 37 weeks or more (P < 0.001). The type of antiretroviral therapy was not
      associated with transmission. Intrapartum therapy was associated with four-fold
      lower MTCT (P = 0.04) in case of virological failure (> 10 000 copies/ml).
      Elective cesarean section tended to be inversely associated with MTCT in the
      overall population, but not in mothers who delivered at term with viral load <
      400 copies/ml [odds ratio (OR), 0.83; 95% CI, 0.29-2.39; P = 0.37]. Among them,
      only duration of antenatal therapy was associated with transmission (OR by week,
      0.94; 95% CI, 0.90-0.99; P = 0.03). CONCLUSIONS: Low maternal plasma viral load
      is the key factor for preventing MTCT. Benefits in terms of MTCT reduction may be
      expected from early antiretroviral prophylaxis. The potential toxicity of
      prolonged antiretroviral use in pregnancy should be evaluated.

PMID- 18097233
TI  - Non-Hodgkin lymphoma incidence in the Swiss HIV Cohort Study before and after
      highly active antiretroviral therapy.
AB  - OBJECTIVE: To assess the long-term effect of HAART on non-Hodgkin lymphoma (NHL)
      incidence in people with HIV (PHIV). DESIGN: Follow-up of the Swiss HIV Cohort
      Study (SHCS). METHODS: Between 1984 and 2006, 12 959 PHIV contributed a total of
      75 222 person-years (py), of which 36 787 were spent under HAART. Among these
      PHIV, 429 NHL cases were identified from the SHCS dataset and/or by record
      linkage with Swiss Cantonal Cancer Registries. Age- and gender-standardized
      incidence was calculated and Cox regression was used to estimate hazard ratios
      (HR). RESULTS: NHL incidence reached 13.6 per 1000 py in 1993-1995 and declined
      to 1.8 in 2002-2006. HAART use was associated with a decline in NHL incidence [HR
      = 0.26; 95% confidence interval (CI), 0.20-0.33], and this decline was greater
      for primary brain lymphomas than other NHL. Among non-HAART users, being a man
      having sex with men, being 35 years of age or older, or, most notably, having low
      CD4 cell counts at study enrollment (HR = 12.26 for < 50 versus >or= 350
      cells/microl; 95% CI, 8.31-18.07) were significant predictors of NHL onset. Among
      HAART users, only age was significantly associated with NHL risk. The HR for NHL
      declined steeply in the first months after HAART initiation (HR = 0.46; 95% CI,
      0.27-0.77) and was 0.12 (95% CI, 0.05-0.25) 7 to10 years afterwards. CONCLUSIONS:
      HAART greatly reduced the incidence of NHL in PHIV, and the influence of CD4 cell
      count on NHL risk. The beneficial effect remained strong up to 10 years after
      HAART initiation.

PMID- 18097234
TI  - HIV dynamics and immunosenescence.
AB  - Three differential equations modelling HIV virion, and infected and uninfected
      immune-cell densities during acute and chronic phases of infection underlie in
      vivo HIV viral dynamics models. Adding a fourth equation that simulates
      immunosenesence through the drawdown of a stem-cell reservoir permits the phase
      of full-blown AIDS to be incorporated in the model. This greatly enhances the
      utility of the model in designing interventions and explains why time-to-full
      blown AIDS decreases with age at infection.

PMID- 18097235
TI  - Combination antiretroviral therapy failure and HIV super-infection.
AB  - In addition to development or selection of resistance, failure to continuously
      suppress HIV-1 production while still using initially effective combination
      antiretroviral therapy (cART) may result from super-infection with a drug
      resistant strain. Both transmission of drug resistant HIV and super-infection
      have been demonstrated. We analysed HIV pol genes obtained before start of
      initially successful cART and during failure while still on cART in 101 patients.
      Difference in precART and cART failure sequences were explained by evolution and
      not by super-infection.

PMID- 18097236
TI  - Prevalence and impact of HIV-1 protease mutation L76V on lopinavir resistance.
AB  - Besides I47A, mutation L76V at the HIV protease gene has recently been proposed
      to cause lopinavir resistance. This change was present in 37 (2.7%) out of 1376
      patients failing protease inhibitor containing regimens. Although 26 (70%) were
      on lopinavir, most had previously failed other protease inhibitors and carried
      multiple protease inhibitor resistance mutations. Therefore, L76V does not appear
      to be a primary lopinavir resistance change when the drug is used in combination
      therapy.

PMID- 18097237
TI  - Stopping antiretroviral therapy: role for therapeutic drug monitoring.

PMID- 18097238
TI  - Preventable zidovudine overdose during postnatal prophylaxis in healthy children
      born to HIV-1-positive mothers.

PMID- 18097239
TI  - Initial spontaneous clearance and re-infection with a distinct hepatitis C virus
      genotype leading to chronic hepatitis C in an HIV+ intravenous drug user.

PMID- 18097240
TI  - An important, but not the first, hepatitis C virus behavioural intervention
      study.

PMID- 18097242
TI  - Comment on Neumann et al. 'Differential antiviral effect of PEG-interferon-alpha
      2b on HIV and HCV in the treatment of HIV/HCV co-infected patients'.

PMID- 18097243
TI  - Representative sampling and analysis in HIV molecular epidemiology studies.

PMID- 18097244
TI  - Withdrawal of Pneumocystis prophylaxis.

PMID- 18097246
TI  - Evaluation of therapeutic response of tuberculoma using F-18 FDG positron
      emission tomography.
AB  - BACKGROUND: Monitoring the response to antituberculosis (anti-TB) treatment can
      be difficult in patients with tuberculoma. We have retrospectively assessed the
      ability of F-18 fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)
      to evaluate the response to anti-TB treatment in patients with tuberculoma.
      METHODS: Two patients with tuberculoma underwent repeat PET scans during anti-TB
      treatment. Changes in maximal standard uptake value (SUV) of the tuberculoma on
      PET images were analyzed between 2 scans. Initial PET scans were performed before
      the start of anti-TB treatment (T0), and later scans were performed after
      completion of treatment (T1). RESULTS: In a 57-year-old female patient with
      clinical TB, maximal SUV of tuberculoma on PET scan decreased from 2.6 (at T0) to
      an undetectable value (at T1) at an interval of 187 days. In a 60-year-old woman
      with biopsy-proven TB, maximal SUV of tuberculoma on PET scan decreased from 4.8
      (at T0) to 1.1 (at T1) at an interval of 192 days. CONCLUSION: PET scans may be
      useful for monitoring responses to anti-TB treatment in patients with
      tuberculoma.

PMID- 18097247
TI  - Malignancy in kaolin pneumoconiosis found with F-18 FDG positron emission
      tomography.
AB  - Kaolin pneumoconiosis may produce radiologic findings similar to those of
      malignancy. Current management includes serial radiologic examination and lung
      sampling of suspicious parenchymal opacities and nodules to exclude associated
      malignancy. This may result in unnecessary pulmonary resections in patients with
      already compromised lung function. In a patient with known kaolin pneumoconiosis
      and multiple nodules, we used positron emission tomography to identify suspicious
      areas for malignancy that were confirmed by open lung biopsy, leading to
      successful lung cancer treatment.

PMID- 18097249
TI  - Radioguided surgical strategy in mucosal melanoma of the nasal cavity.
AB  - Sinonasal mucosal melanoma (MM), although very rare (<1% of the all MM), is
      second only to squamous cell carcinoma among cancers of the nasal region and
      still represents a challenging problem in head and neck cancer. A 60-year-old
      woman had nasal MM stage I, which was treated with concomitant probe-guided tumor
      excision and an elective neck dissection after sentinel lymph node biopsy. The
      radioactivity status of the tumor and lymph nodes were compared with the
      histopathologic specimen. Surgical margins, sentinel lymph node, and
      lymphadenectomy were free of tumor. The patient was seen in frequent and regular
      follow-up and was free of disease without any other treatment (radiotherapy,
      immunotherapy, or chemotherapy). Radioguided surgery is an easy and reproducible
      surgical technique that could increase the likelihood of adequate excision and
      minimize the development of nodal disease by performing a "guided" neck
      dissection after the sentinel lymph node biopsy. A multidisciplinary approach and
      further studies with a longer follow-up are needed to substantiate the accuracy
      and safety of this strategy in the treatment of an aggressive neoplasm like MM of
      the head and neck, which still has a very poor prognosis.

PMID- 18097248
TI  - F-18 FDG PET and PET/CT evaluation of response to chemotherapy in bone and soft
      tissue sarcomas.
AB  - OBJECTIVE: F-18 FDG PET has been used to grade sarcomas and assess response to
      therapy in advanced disease. Certain chemotherapy agents are thought to induce an
      inflammatory response in the tumor bed that can make interpretation of post
      therapy FDG PET scans difficult. A review of our experience with PET in assessing
      therapy response in osseous and soft tissue sarcomas (OSTS) is presented.
      METHODS: This is a retrospective study (January 1999 to December 2004) of 14
      patients with histologic diagnosis of OSTS, who had 2 consecutive PET
      examinations for evaluation of chemotherapy response. The group included 8 men
      and 6 women, with age range of 18 to 56 years (average, 36 +/- 14).
      Semiquantitative assessment of FDG uptake was performed by calculating maximum
      standard uptake value (SUVmax) before and after treatment. The response to
      therapy was assessed independently by tumor necrosis at post-therapy surgery and
      according to European Organization for Research and Treatment of Cancer (EORTC)
      criteria for PET. The follow-up PET examinations were performed at an interval of
      28 to 166 days (average, 90 +/- 45). All patients ended the ifosfamide regimen at
      7 to 36 (average, 16 +/- 9) days before the follow-up PET scans. Five of them
      received methotrexate, adriamycin, and/or cisplatin as well. RESULTS: Based on
      the EORTC criteria alone, 3 patients (21.4%) had progression of disease (increase
      in SUVmax of 29%-69%; mean, 48% +/- 20%), 5 patients (35.7%) had stable disease,
      and 6 patients (42.8%) had partial response (decrease in SUVmax of 27%-84%; mean,
      62% +/- 23%). Across all patients, the tumor necrosis postchemotherapy ranged
      from 5% to 100% (mean, 64% +/- 34%). In 8 patients (57.1%) the tumor necrosis
      correlated with the SUVmax changes. However, for 3 patients, the SUVmax changes
      indicated partial response despite necrosis of fewer than 90% of the surgical
      specimens, whereas 3 patients with >90% tumor necrosis had SUVmax changes
      indicative of stable disease. CONCLUSION: The pathologically determined degree of
      necrosis postneoadjuvant chemotherapy was concordant with PET-assessed EORTC
      classification of response in 57.1% of the cases. However, a significant number
      of patients had discrepancies, which may be in part explained by chemotherapy
      induced inflammation. The latter should be considered during post-therapy PET
      interpretation in OSTS.

PMID- 18097250
TI  - Follow-up FDG PET in the evaluation of unexplained focal activity in the abdomen.
AB  - PURPOSE: This study assessed the value of a follow-up FDG PET scan when the
      initial PET demonstrated unexplained findings of focal FDG uptake in the abdomen.
      METHOD: The records of 3634 patients with PET scans were retrospectively
      reviewed. Those patients who had follow-up PET scans after the initial PET scan
      showed unexplained FDG activity in the abdomen were further analyzed. The results
      from the second PET scan were compared with the follow-up data, which included
      the findings from other imaging modalities, clinical course, and biopsy or
      surgical pathology interpretations. RESULTS: A total of 59 patients were included
      in the final analysis. The average time interval between the initial and the
      follow-up PET scans was 4.2 + 2.3 months. The follow-up PET provided a clear-cut
      diagnosis in 55 (93.2%) of these patients, whereas diagnoses in only 4 patients
      remained indeterminate. Follow-up PET scans were negative for abdominal
      malignancy in 38 patients. Thirty-five of these 38 patients with negative follow
      up PET were proven to be without abdominal malignancy, with a negative predictive
      value of 92.1% (35 of 38). The follow-up PET was positive in 17 patients. Fifteen
      of these 17 patients with a positive follow-up PET scans were found to have
      malignancy in the abdomen with a positive predicative value of 88.2% (15 of 17).
      All 4 patients with indeterminate follow-up scans were proven not to have
      malignancy. CONCLUSION: Follow-up FDG PET scan provides an effective means for
      diagnosing unexplained findings in the abdomen that were previously detected on
      initial PET scan.

PMID- 18097251
TI  - Silent parathyroid adenoma mistakenly interpreted on FDG-PET as thyroid cancer
      metastasis in a patient with elevated thyroglobulin and negative I-131 whole body
      scan and removed by radioguided minimally invasive surgery.
AB  - Detection of recurrent and metastatic thyroid cancer remains a considerable
      challenge in patients presenting with rising thyroglobulin levels but with
      negative I-131 whole body scintigraphy. Such is the case in this patient with
      follicular thyroid cancer in whom subsequent FDG PET scanning showed a solitary
      hypermetabolic cervical lesion. With definitive management and multidisciplinary
      approach in mind, radioguided surgical excision came into play through the use of
      Tc-99m sestamibi, leading to successful removal of the lesion. Histopathology,
      however, revealed a parathyroid adenoma. This highlights the importance of
      considering differential diagnoses in apparent cases of recurrence to avoid
      potential pitfalls.

PMID- 18097252
TI  - Bronchoalveolar carcinoma of lung masquerading as iodine avid metastasis in a
      patient with minimally invasive follicular carcinoma of thyroid.
AB  - A 52-year-old man with follicular thyroid carcinoma was administered 182 mCi of
      radioiodine (I-131) a month after total thyroidectomy. Post-therapy scan revealed
      diffuse uptake of radioiodine in the apical left lung. CT-guided biopsy of this
      mass revealed mucinous bronchoalveolar carcinoma. Immunohistochemistry for
      thyroglobulin was negative. An FDG PET scan showed avid uptake in the lung mass.
      Surgery was ruled out, so he was given chemotherapy, without benefit. The lesion
      continued to show I-131 uptake even while on daily T3 substitution, suggesting
      that the mass was thyroid stimulating hormone-independent. Because the mass
      showed I-131 uptake and chemotherapy was not beneficial, it was decided to treat
      with I-131. He was continued on T3 substitution therapy and was given 209 mCi of
      I-131. Follow-up CT scan a few weeks later reported a 1-cm all round reduction of
      the mass. I-131 scan showed avid tracer uptake in the mass. This case suggests
      the possibility of this therapeutic option in nonthyroidal tumors that may
      concentrate radioiodine.

PMID- 18097253
TI  - Sacral nerve root neurolymphomatosis diagnosed on FDG-PET/CT and magnetic
      resonance imaging.
AB  - A 67-year-old male with transformed diffuse large B cell lymphoma presented with
      severe neuropathic-type pain radiating down his posterior right thigh. Initial
      lumbar radiographs and MRI of the lumbar spine failed to identify a cause for his
      symptoms. A FDG-PET/CT scan demonstrated increased focal FDG uptake in the right
      sacral (S2) nerve root. Review of the lumbar spine MRI performed 6 days earlier
      demonstrated abnormal right S2 nerve root enhancement. The combined FDG-PET/CT
      and MRI findings allowed a presumptive diagnosis of neurolymphomatosis. However,
      the patient succumbed to his illness before planned local radiotherapy could be
      performed.

PMID- 18097254
TI  - Enhanced detectability of recurrent brain tumor using glucose-loading F-18 FDG
      PET.
AB  - A 43-year-old man with a history of lung cancer, brain metastasis, and gamma
      knife radiosurgery underwent FDG PET/CT to differentiate recurrence from
      radiation necrosis. Basal PET/CT scan showed equivocal uptake in the margin of
      necrotic tumor. After glucose loading (10% glucose 50 mL for 5 minutes), marginal
      FDG uptake was more easily depicted. Proton magnetic resonance spectroscopy (1H
      MRS) showed increased Cho/Cr ratio (1.7), which was consistent with tumor
      recurrence. The patient underwent whole brain radiotherapy thereafter. It is
      implicated that hyperglycemia-induced reduction of glucose uptake in recurrent
      brain tumors was less than in a normal brain, resulting in higher tumor-to-gray
      matter ratio.

PMID- 18097255
TI  - Effect of nilvadipine on regional cerebral blood flow in a patient with early
      Alzheimer disease.
AB  - Hypertension in an 83-year-old woman with early Alzheimer disease was treated
      with a calcium channel blocker, nilvadipine, for 3 months. Before and after
      nilvadipine treatment, global and regional cerebral blood flow (gCBF and rCBF)
      were measured using Tc-99m ethyl cysteinate dimer SPECT. This treatment elevated
      both the Mini-Mental State Examination score from 23 to 27 and gCBF from 37.6 to
      42.0 mL/100 g/min. This treatment also elevated rCBF prominently in the bilateral
      frontal cortex, right parietal cortex, and posterior cingulate cortex. These
      areas with rCBF increase generated by subtraction of pretreatment SPECT from post
      treatment SPECT were demonstrated on a coregistered MRI.

PMID- 18097256
TI  - Compartment syndrome caused by computed tomography contrast infiltration seen on
      a Tc-99m methylene diphosphonate bone scan.
AB  - A 72-year-old man was hospitalized for transurethral resection of bladder cancer.
      Two days after the procedure, the patient continued to have gross hematuria and a
      computed tomography (CT) scan of the abdomen and pelvis with intravenous contrast
      was performed to check the integrity of the resection site. Later that day, the
      patient underwent technetium-99m methylene diphosphonate (MDP) bone scintigraphy
      to investigate the possibility of bone metastasis. The bone scan showed no signs
      of metastasis but did reveal increased uptake of the left hand and forearm on the
      opposite side of the injection site.

PMID- 18097257
TI  - Tc-99m HMPAO labeled white blood cell imaging in a child with eosinophilic lung
      disease.
AB  - In radiolabeled leukocyte imaging, Tc-99m HMPAO has a significantly higher
      selectivity for eosinophils than neutrophils, but this may be clinically
      meaningful in disorders with eosinophilic infiltration. We present the case of a
      2-year-old boy with infection who also developed drug-induced eosinophilic lung
      disease, as established later by bronchoalveolar lavage and discontinuation of
      the responsible antistaphylococcal agent. In the investigation of sepsis,
      diffusely increased pulmonary accumulation of Tc-99m HMPAO labeled leukocytes was
      observed. These findings were consistent with eosinophilic lung infiltration and
      underline the importance of clinical and laboratory data in the comprehensive
      interpretation of Tc-99m HMPAO labeled leukocytes scans.

PMID- 18097258
TI  - Ga-67 and CT fusion imaging of an infected aortic graft.
AB  - A 17-year-old girl with a background of aortic coarctation repaired with
      insertion of a prosthetic graft presented with persisting fever and nonspecific
      back pain. Whole body Ga-67 scintigraphy was performed to evaluate occult
      infection. Intense uptake was noted in the region of the superior mediastinum.
      Fusing Ga-67 tomographic reconstruction with CT images allowed accurate
      determination of the area of enhanced uptake to be at the site of the aortic
      graft.

PMID- 18097259
TI  - Biliary leak in a child after liver transplant and value of delayed images.
AB  - A 2-year-old child underwent liver transplant and was referred for postsurgical
      abdominal pain. Hepatobiliary scintigraphy with Tc-99m iminodiacetic acid (IDA)
      was performed and with the help of 24-hour delayed images, the diagnosis of
      biliary leak at the site of anastomosis was made possible. This case report
      confirms the value of delayed images to facilitate the diagnosis in unequivocal
      situations and reminds us of the usefulness of this noninvasive method,
      especially in pediatrics.

PMID- 18097260
TI  - Increased activity on In-111 octreotide imaging due to radiation fibrosis.
AB  - Indium-111 octreotide scintigraphy is a useful investigation in the diagnosis and
      staging neuroendocrine or nonendocrine malignancies such as carcinoid,
      granulomas, small cell lung cancer, medullary thyroid carcinoma, and others.
      Tumors with large numbers of somatostatin receptors can be accurately imaged and
      this can be useful in guiding treatment. Although uncommon, false-positives
      studies have been reported and often the cause is unexplained but assumed to be a
      high number of somatostatin receptors in other pathology. We present a case with
      increased uptake resulting in a scan due to pulmonary fibrosis.

PMID- 18097261
TI  - Systemic disseminated tuberculosis mimicking malignancy on F-18 FDG PET-CT.
AB  - FDG PET-CT imaging is increasingly accepted as a modality for evaluation of many
      malignancies, but FDG also can be accumulated intensely by inflammatory lesions.
      We present a case of a 60-year-old woman with intermittent fever, chills,
      fatigue, and dyschezia. CT scans indicated colon carcinoma with thoracic and
      retroperitoneal lymph node metastases. Whole body FDG PET-CT was performed to
      confirm and stage the malignant disease and showed intense FDG uptake in those
      lesions. However, histopathology confirmed tuberculosis. The literature
      describing FDG accumulation in constitutional tuberculous lesions is sparse, and
      one must be aware of patterns of FDG accumulation in tuberculosis in the
      diagnosing malignancies.

PMID- 18097262
TI  - FDG PET in Lhermitte-Duclos disease.
AB  - A 45-year-old man presented with a headache. The medical history included a
      partial thyroidectomy, a colon polypectomy, and stomach tumors (all benign
      adenomas) 34, 2, and 1 year earlier, respectively. CT showed a space-occupying
      lesion in the left cerebellar hemisphere with calcification. The mass showed a
      striated pattern of hyperintensity on T2-weighted images. An FDG-PET scan was
      performed after the intravenous administration of 250 MBq (6.8 mCi) F-18 FDG. The
      images of the brain showed a hypermetabolic area in the left cerebellar
      hemisphere. The whole body images showed no abnormal accumulation other than
      physiologic uptake. A presumptive diagnosis of Lhermitte-Duclos disease (LDD) was
      made.

PMID- 18097263
TI  - The "hot nose" sign on brain death nuclear scintigraphy: where does the flow
      really go?
AB  - Nuclear scintigraphy has been used in patients with brain death since the 1970s.
      Many studies report a "hot nose" sign as predictive of brain death and lack of
      cerebral flow. Current nuclear medicine textbooks state that increased flow to
      the nose occurs secondary to occlusion of the internal carotid artery with flow
      rerouted to the nose via the external carotid artery. This explanation has been
      provided for decades assuming that the blood flow is actually increased to the
      nose. We performed a study to determine whether flow is really seen in the nose
      when a hot nose sign is present.

PMID- 18097264
TI  - Lithotomy position-related rhabdomyolysis of gluteus maximus muscles demonstrated
      by bone scintigraphy.
AB  - Major urologic surgery performed in the lithotomy position sometimes results in
      the serious complications of rhabdomyolysis and acute renal failure. A 54-year
      old man with prostate cancer (weight, 84 kg; height, 171 cm; body mass index,
      28.7) underwent radical perineal prostatectomy in the lithotomy position for 7
      hours. On the first postoperative day, the patient complained of numbness and
      pain of both thighs with oliguria. Serum creatinine kinase and myoglobin levels
      were elevated. Bone scintigraphy on the second day, which was confirmed by MRI,
      showed extraosseous increased activity in gluteus maximus muscle regions
      compatible with rhabdomyolysis.

PMID- 18097265
TI  - Chronic recurrent multifocal osteomyelitis demonstrated by Tc-99m methylene
      diphosphonate bone scan.
AB  - A 12-year-old Middle Eastern girl presented with abdominal pain, weight loss, and
      intermittent pain in both thighs. She was initially suspected of Crohn disease,
      but this diagnosis was excluded after extensive gastromedical evaluation. Plain x
      rays of the femora were normal, whereas the initial Tc-99m methylene
      diphosphonate (MDP) bone scan showed several foci with increased activity in both
      femurs. MR scan showed excessive periostal inflammatory and mild intramedullary
      changes in both femurs. A percutaneous bone biopsy demonstrated changes
      consistent with chronic recurrent multifocal osteomyelitis (CRMO). The patient's
      symptoms disappeared spontaneously, but reappeared 1.5 years later, which led to
      a new MDP bone scan that showed normal findings.

PMID- 18097266
TI  - Baker cyst as seen on a PET/CT scan.
AB  - We present the case of a 48-year-old woman who had been diagnosed with multiple
      myeloma a year ago. She had persistent pain in her right knee that she tended to
      ignore. As part of her follow-up she underwent a PET/CT scan that did not show
      any metastatic lesions. However, a focal rounded area of FDG uptake behind her
      right knee showed a fluid density on the CT scan. A presumptive diagnosis of
      Baker cyst was suggested. Review of her previous MRI report performed at another
      hospital corroborated this finding.

PMID- 18097267
TI  - Diagnosis of venous angiosarcoma by FDG PET/CT.
AB  - A 56-year-old man with diffuse large cell lymphoma underwent posttherapy F-18
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT).
      A new focus of intense uptake was detected in contact with the left external
      iliac vein. This was biopsied and diagnosed as an angiosarcoma of the external
      iliac vein.

PMID- 18097268
TI  - Zoledronate-related osteonecrosis of the mandible.
AB  - We report the PET-CT appearance of Zoledronate-related osteonecrosis of the
      mandible in a 54-year-old woman with right breast cancer with osseous and
      pulmonary metastases. Her treatment included surgery, chemotherapy and
      Zoledronate, and external beam radiation treatment. During the course of
      treatment, the patient developed osteonecrosis of the jaw secondary to
      Zoledronate, which was biopsy-proven, for which Zoledronate was discontinued
      shortly after. Hybrid PET-CT was performed approximately 1 year after the
      discontinuation of Zoledronate. PET-CT images demonstrated diffuse, intense
      hypermetabolism in the mandible, consistent with documented osteonecrosis.

PMID- 18097269
TI  - Varying appearance of focal nodular hyperplasia in nuclear medicine imaging.
AB  - The focal nodular hyperplasia (FNH) is the second most common benign hepatic
      tumor, which contains variable quantities of normal hepatic cellular elements:
      Kupffer cells, hepatocytes, bile ducts, and blood vessels. Two patients with
      suspicion of FNH were investigated by colloidal, blood pool, and hepatobiliary
      scintigraphy. Dynamic perfusion examination (with labeled RBCs), planar and SPECT
      studies were performed in all cases. Diagnosis was confirmed by histologic
      examination. We suggest the importance of combined imaging because of various
      appearance of the tumor. In our experience SPECT imaging after a planar study is
      a useful sequence, especially in small tumors in the exact location of activity.

PMID- 18097270
TI  - Current readings in nuclear medicine.

PMID- 18097271
TI  - Addition of the long-axis information to short-axis contours reduces interstudy
      variability of left-ventricular analysis in cardiac magnetic resonance studies.
AB  - OBJECTIVES: To reduce interstudy variability using long-axis information for
      correcting short-axis (SA) contours at basal and apical level for left
      ventricular analysis by magnetic resonance imaging. MATERIALS AND METHODS: A
      total of 20 patients with documented heart failure and 20 volunteers underwent
      magnetic resonance imaging examination twice for measuring endocardial end
      diastolic volume, endocardial end-systolic volume, mass, and ejection fraction.
      The boundary of the left ventricle, the mitral valve plane, and apex were marked
      manually on the 2- and 4-chamber long-axis images. Automatic epicardial and
      endocardial contour detection was performed on the SA images using the
      intersection of the outlines from the long axis as starting positions. The same
      observer compared the interstudy variability of this method with analysis that
      was based on the SA images only. RESULTS: The interstudy variability decreased
      when information from the long axis was included; for end-systolic volume, 9.6%
      versus 4.7% (P = 0.00014); for end-diastolic volume, 4.9% versus 2.5% (P =
      0.0011); for mass, 7.4% versus 5.0% (P = 0.11); and for ejection fraction 12.2%
      versus 5.6% (P = 0.0017), respectively. CONCLUSIONS: Identification of the mitral
      valve plane and apex on long-axis images to limit the extent of volume at the
      base and the apex of the heart reduces interstudy variability for left
      ventricular functional assessment.

PMID- 18097272
TI  - In vivo T2-weighted magnetic resonance imaging can accurately determine the
      ischemic area at risk for 2-day-old nonreperfused myocardial infarction.
AB  - OBJECTIVES: To determine whether in vivo T2-weighted cardiac magnetic resonance
      imaging (MRI) delineates the area at risk (AAR) in 2-day-old nonreperfused
      myocardial infarction (MI). AAR was defined as the size of the perfusion defect
      on day 0. MI and the residual ischemic viable border zone comprise the AAR.
      MATERIALS AND METHODS: Fourteen dogs with permanent coronary artery occlusion
      were imaged on day 0 and day 2. The size of the AAR as measured by first-pass
      magnetic resonance perfusion on day 0 was compared with retrospectively
      determined AAR using day 2 T2-weighted MRI. Triphenyltetrazolium chloride
      staining was used to measure infarct size. Microspheres were used to detect
      residual perfusion. RESULTS: Hyperintense zones on day 2 T2-weighted magnetic
      resonance images accurately depicted the AAR as measured by first-pass perfusion
      on day 0 (38.9 +/- 3.0 vs. 36.3% +/- 3.3% of left ventricular, P = 0.07). Good
      correlation (R = 0.91) and Bland-Altman agreement was observed between the AAR
      measurements and the corresponding T2-weighted hyperintense regions. Both
      measures of AAR were larger than the infarcted zone (25.6% +/- 2.5% of left
      ventricular area; P < 0.001). CONCLUSIONS: Hyperintense regions visualized with
      in vivo T2-weighted cardiac MRI allow determination of the AAR 2 days
      postinfarction in nonreperfused MI.

PMID- 18097273
TI  - Systematic variation of off-resonance prepulses for clinical magnetization
      transfer contrast imaging at 0.2, 1.5, and 3.0 tesla.
AB  - OBJECTIVES: The aim of the presented study was to evaluate pulsed magnetization
      transfer contrast (MTC) effects using saturation pulses of variable off-resonance
      frequency and radio frequency (RF) amplitude for a variety of tissue types (white
      and gray matter, liver, kidney, spleen, muscle, and articular cartilage) in human
      subjects at field strengths of 0.2, 1.5, and 3.0 Tesla. MATERIALS AND METHODS:
      MTC imaging studies of the head, knee, and abdomen were performed using an
      adapted multiple MTC (mMTC) module in 3 healthy volunteers for all field
      strengths. This mMTC pulse module applies a variable Gaussian shaped
      magnetization transfer (MT) saturation pulse in a proton-density weighted RF
      spoiled gradient echo sequence. It allows for both a flexible MT pulse design and
      performance of consecutive measurements with variation of amplitude and off
      resonance frequency, whereas keeping other MT pulse parameters unchanged.
      Magnetization transfer signal ratio (MTR) maps were calculated on a pixel-by
      pixel basis. Additional mMTC imaging measurements were performed using an agar
      water phantom. For assessment of undesired direct saturation effects of the MT
      pulse on the water pool, numerical simulations based on Bloch's equations were
      performed and analyzed. RESULTS: The results indicate that MTR values for given
      MT pulses (pulse shape, off-resonance frequency and flip angle) are larger at
      higher magnetic field strengths. For white matter, gray matter, cartilage, and
      muscle, an increase of 10% to 30% was found at 3.0 T when compared with 1.5 T.
      Low magnetic field strength of 0.2 T led to MTR values of one third to half the
      values at 1.5 T. MTR values for abdominal tissues were partly lower at 3.0 T
      compared with 1.5 T, which might be related to reduced B1 field strengths at 3.0
      T due to dielectric effects. CONCLUSIONS: The increased MT effect at a higher
      field strength can partly compensate the specific absorption rate related
      problems in MTC applications. It is shown that for flip angles of 700 degrees to
      900 degrees and offset frequencies of 1000 Hz to 1500 Hz, high quality MTR maps
      could be obtained at an acceptable level of direct saturation for all field
      strengths. Furthermore, if the better signal-to-noise ratio at higher magnetic
      fields is taken into account, quality of MTR maps of the head and the knee at 3.0
      T was clearly improved compared with lower fields under optimized and comparable
      conditions.

PMID- 18097274
TI  - Cervical CT angiography comparing routine noncontrast and a late venous scan as
      masks for automated bone subtraction: feasibility study and examination of the
      influence of patient motion on image quality.
AB  - OBJECTIVES: Bone subtraction techniques have been shown to enhance cranial
      computed tomography angiography (CTA). The aims of this study were to assess the
      feasibility of bone subtraction CTA (BSCTA) in cervical CTA, test whether a late
      venous CT (LVCT) scan can be used as bone mask instead of a low-dose nonenhanced
      CT (NECT), and to evaluate the impact of patient motion on image quality.
      MATERIALS AND METHODS: Thirty-six patients underwent BSCTA for the evaluation of
      the neck vessels with a 64-slice CT system using commercially available software.
      Eighteen patients had a low-dose NECT scan before CTA, and 18 patients had an
      LVCT scan after CTA. Subtraction quality for vascular segments was evaluated
      independently by 2 examiners. Cohen's Kappa was applied to evaluate interobserver
      reliability, and Wilcoxon signed rank test was used to test for differences
      between the 2 groups. Motion between the 2 scans was measured and correlated to
      image quality. RESULTS: BSCTA using both NECT and LVCT scans as masks was
      successfully applied in all patients. Image quality did not differ significantly
      between the 2 groups, and interobserver agreement was high (k 0.5-1). Motion
      between the scans was highest for the jaw and hyoid, and lowest for the upper and
      lower spine. Decreased image quality on the subtracted images was associated with
      increased motion for the external carotid and vertebral artery, independent of
      mask type (P = 0.002-0.04). CONCLUSIONS: BSCTA techniques can be successfully
      applied in the neck. If parenchymal phase imaging is indicated, the LVCT can be
      used as a bone subtraction mask and diagnostic scan, eg, for tumor imaging.

PMID- 18097275
TI  - Targeting liver lesions for radiofrequency ablation: an experimental feasibility
      study using a CT-US fusion imaging system.
AB  - PURPOSE: To investigate the feasibility and validity of real-time guidance using
      a fusion imaging system that combines ultrasound (US) and computed tomography
      (CT) in the targeting and subsequent radiofrequency (RF) ablation of a liver
      target inconspicuous on US. METHODS AND MATERIALS: The study was designed as an
      experimental ex vivo study in calf livers with radiopaque internal targets,
      inconspicuous at US, simulating a focal liver lesion. The study included 2
      phases. The initial phase was to examine the feasibility of matching
      preprocedural volumetric CT data of the calf livers with real-time US using a
      commercially available multimodality fusion imaging system (Virtual Navigator
      System, Esaote SpA, Genoa, Italy), and to assess the accuracy of targeting using
      a 22 gauge cytologic needle. The second phase of the study was to validate such a
      technique using a 15 gauge RF multitined expandable needle (RITA Medical Systems,
      Mountain View, CA) and to examine the accuracy of the needle placement relative
      to the target. The tip of the trocar of the RF needle had to be placed 1 cm from
      the target and then the hooks had to be deployed to 3 cm. Unenhanced CT of the
      liver and multiplanar reconstructions were performed to calculate accuracy of
      positioning, ie, the lateral distance between the needle and the target, the
      distance between the tip of the trocar of the RF electrode and the target, and
      the lateral distance between the central tine of the RF electrode and the target.
      RESULTS: All calf livers underwent successful CT-US registration with a mean
      registration error of 3.0 +/- 0.1 mm and 2.9 +/- 0.1 mm in the initial and second
      phase of the study, respectively. In the initial phase an overall number of 24
      insertions were performed after the US-CT guidance. The mean needle to target
      distance was 1.9 +/- 0.7 mm (range, 0.8-3.0 mm). In the second phase an overall
      number of 12 ablations were performed. The mean target-trocar distance was 10.3
      +/- 2.6 mm. The mean target-central tine lateral distance was 3.9 +/- 0.7 mm
      (range, 2.9-5.1 mm). After the dissection of the specimen the target was found
      unchanged in the center of the ablation zone in all cases. CONCLUSION: Real-time
      registration and fusion of preprocedure CT volume images with intraprocedure US
      is feasible and accurate. The study was however conducted in an ideal
      experimental setting, without patient movements and breathing, and further
      studies are warranted to validate the system under clinical conditions.

PMID- 18097276
TI  - MRI-measurement of perfusion and glomerular filtration in the human kidney with a
      separable compartment model.
AB  - OBJECTIVES: Recent animal studies with dynamic contrast enhanced magnetic
      resonance imaging have demonstrated that a separable compartment model provides
      more accurate assessments of glomerular filtration than the Patlak model. In this
      study, the feasibility of the separable compartment model for the measurement of
      perfusion and filtration in healthy humans is investigated. METHODS: Dynamic
      contrast enhanced magnetic resonance imaging was performed in 15 healthy
      volunteers. Contrast enhancement curves were analyzed with the separable
      compartment model on whole kidney regions, cortex regions, and the pixel level.
      The region of interest values for the kinetic parameters were compared with those
      obtained from the Patlak model and from a model-free deconvolution analysis.
      RESULTS: The separable compartment model provides a good fit to the data over the
      entire dynamic range. All values of filtration (30 +/- 7.2 and 20 +/- 11 mL/100
      mL/Min for kidney and cortex, respectively) are significantly higher than those
      of the Patlak model (24 +/- 6.4 and 15 +/- 11 mL/100 mL/Min). Values produced by
      the Patlak model have a higher variability. Whole kidney values of perfusion (229
      +/- 57 mL/100 mL/Min) are significantly higher than those of a deconvolution
      analysis (210 +/- 50 mL/100 mL/Min). CONCLUSIONS: The separable compartment model
      is feasible for application in humans and sufficiently robust for a pixel
      analysis. Increased filtration values compared with the Patlak model suggest that
      the difference in accuracy observed in animal studies is relevant in humans.
      Increased perfusion values suggest that the separable compartment model corrects
      for known underestimations in the deconvolution analysis.

PMID- 18097277
TI  - Targeted contrast agent helps to monitor advanced plaque during progression: a
      magnetic resonance imaging study in rabbits.
AB  - OBJECTIVE: Gadofluorine M has been reported to enhance early atherosclerotic
      plaque signals in magnetic resonance imaging (MRI). The aim of this study was to
      examine the use of Gadofluorine M to monitor the progression of advanced plaques
      in a rabbit model. METHODS: Focal advanced atherosclerosis was induced in the
      right femoral arteries of 6 New Zealand white rabbits using a combination of
      cholesterol-enriched diet, and sequential air-desiccation, and balloon
      overstretch injury. MRI with conventional 3 contrasts (T1, T2, and proton density
      [PD]) was performed to monitor the progression of the atherosclerotic plaques
      with 2 MRI scans separated by 4 to 8 weeks. Gadofluorine M was given
      intravenously to the rabbits 24 hours before the first MRI scans, and before (n =
      3) or during (n = 3) the second MRI scan. The left femoral arteries were used as
      a control. Histopathologic images localized individual plaque components.
      RESULTS: The advanced plaque displayed multilayered neointima that included foam
      cells, smooth muscle cells, and extracellular matrix. The separate image
      contrasts offered similar T1-weighted enhancement patterns, but the combination
      of all 3 contrasts helped to delineate plaque and lumen boundaries. Gadofluorine
      M strongly enhanced neointima areas with an image contrast (contrast-to-noise
      ratio [CNR]) of approximately 15, versus 2 in the control femoral arterial wall.
      With improved images, significant changes in neointima and total plaque volumes
      over the 4 to 8 weeks between scans could be identified. Gadofluorine M remained
      within the plaques with significant image enhancements (contrast-to-noise ratio =
      5.8) for 2 months after a single injection. CONCLUSION: This preliminary study in
      rabbits indicated that Gadofluorine M provides specific enhancements of
      components associated with advanced atherosclerotic plaques and may help to
      monitor the progression of the plaque in a rabbit model of atherogenesis.

PMID- 18097278
TI  - Classification of small contrast enhancing breast lesions in dynamic magnetic
      resonance imaging using a combination of morphological criteria and dynamic
      analysis based on unsupervised vector-quantization.
AB  - PURPOSE: To evaluate the diagnostic value of breast magnetic resonance imaging
      (MRI) in small focal lesions using dynamic analysis based on unsupervised vector
      quantization in combination with a score for morphologic criteria. MATERIALS AND
      METHODS: We examined 85 mammographically indetermintate lesions (BIRADS 3-4; 47
      malignant, mean lesion size 1.2 cm; 38 benign, mean lesion size 1.1 cm). MRI was
      performed with a dynamic T1-weighted gradient echo sequence (1 precontrast and 5
      postcontrast series). Lesions with an initial contrast enhancement >/=50% were
      selected with semiautomatic segmentation. For conventional dynamic analysis, we
      calculated the mean initial signal increase and postinitial course of all voxels
      included in a lesion. Secondly, all voxels within the lesions were assigned to 4
      clusters using minimal-free-energy vector quantization. Dynamic and morphologic
      criteria were summarized in a diagnostic score and evaluated by receiver
      operating characteristic analysis. RESULTS: In the present collection of small
      lesions, morphologic criteria [area under the curve (AUC) = 0.610] were inferior
      to dynamic criteria in the detection of breast cancer. Dynamic analysis with
      vector quantization (AUC = 0.760) presented slightly better results compared with
      standard dynamic analysis (AUC = 0.693). There was no benefit for combined
      morphologic and dynamic analysis. CONCLUSION: In small MR-mammographic lesions,
      dynamic analysis with vector quantization alone tends to result in a higher
      diagnostic accuracy compared with combined morphologic and dynamic analysis.

PMID- 18097279
TI  - A preclinical study to investigate the development of nephrogenic systemic
      fibrosis: a possible role for gadolinium-based contrast media.
AB  - OBJECTIVES: Several recent publications have suggested an association between the
      administration of gadolinium (Gd)-based contrast agents and the occurrence of
      Nephrogenic Systemic Fibrosis (NSF), an acquired disorder marked by skin
      thickening and fibrosis occurring in patients with severe renal dysfunction. The
      aim of this study was to establish a preclinical experimental setting to
      investigate the possible link between NSF and Gd-based contrast agents, and
      specifically the role of Gd and/or depletion of endogenous metal ions as possible
      triggers for NSF. MATERIALS AND METHODS: Thirty-five healthy male rats received
      repeated intravenous injections of Magnevist (gadopentetate dimeglumine; Gd
      DTPA), Omniscan (gadodiamide; Gd-DTPA-BMA), or gadodiamide without caldiamide at
      a dose of 2.5 mmol Gd/kg body weight over at least 20 days to simulate the
      exposure to Gd-containing contrast agents in patients with severe renal
      dysfunction. In addition, caldiamide (the excess ligand in Omniscan) and Gd
      ethylenediamine tetraacetic acid (Gd-EDTA) as a positive control, and saline as a
      negative control were studied. Histopathologic and immunohistochemical analysis
      of the skin was performed. Gd and zinc concentrations were measured in skin,
      femur, and liver tissue by atomic emission spectrometry. RESULTS: Rats receiving
      Gd-EDTA, gadodiamide without caldiamide, and Omniscan developed epidermal
      ulceration and acanthosis, dermo-epidermal clefts, minimal-to-slight dermal
      fibrosis, and increased dermal infiltration of different cells, partly positive
      for CD34 fibrocytes. No such NSF-like macroscopic lesions were observed in the
      saline, caldiamide, and Magnevist groups. High Gd concentrations in the skin were
      found in the Gd-EDTA, gadodiamide without caldiamide, and Omniscan groups. In the
      Magnevist group, Gd levels in the skin were 10-times lower than in the Omniscan
      treated animals but elevated compared with saline. CONCLUSIONS: A preclinical
      experimental setting has been established where NSF-like lesions could be
      observed. The link between the application of Gd-based contrast media and the
      induction of NSF-like lesions was established. The data indicate that the
      observed skin lesions are related to the release of Gd and not to the depletion
      of endogenous ions. The investigations further suggest potential importance of
      the stability of Gd-based contrast agents.

PMID- 18097281
TI  - Claudin-1 and its potential role in HCV entry: another piece of the puzzle.

PMID- 18097282
TI  - Gastric and enteric involvement in progressive systemic sclerosis.
AB  - Progressive systemic sclerosis (PSS) is a chronic multisystem disease
      characterized by excess deposition of connective tissue in skin and internal
      organs, associated with microvasculature changes and immunologic abnormalities.
      Involvement of the gastrointestinal tract may occur in 2 stages, a neuropathic
      disorder followed by a myopathy. Gastric emptying is delayed in 10% to 75% of
      patients and correlates with symptoms of early satiety, bloating, and emesis.
      Compliance of the fundus is increased although perception of fullness is normal.
      Myoelectric abnormalities have been found in some studies. Treatments include
      metoclopramide, cisapride, and erythromycin. Bleeding from telangiectasias and
      watermelon stomach is treated endoscopically. Small bowel involvement in PSS
      occurs in 17% to 57% of patients. The migrating motor complexes are reduced or
      absent, predisposing to bacterial overgrowth. Malabsorption may also be due to
      pancreatic insufficiency. Barium enemas demonstrate pancolonic involvement in 10%
      to 50% of patients with PSS. Wide-mouthed diverticuli, involving all layers of
      the intestinal wall, are characteristic. Pseudoobstruction may respond to
      octreotide or prucalopride therapy. Complications include pneumatosis cystoides
      intestinalis, stercoral ulcerations, and perforation. Fecal incontinence may be
      due to dysfunction of the internal anal sphincter, a smooth muscle responsible
      for most of the resting anal sphincter pressure. Anal manometry may show a
      reduction or loss of the rectoanal inhibitory reflex. Treatments include
      biofeedback, sacral nerve stimulation, and surgery. PSS involves the
      gastrointestinal tract from the mouth to the anus. Studies are needed to define
      effective treatments in these diseases, which cause great morbidity.

PMID- 18097283
TI  - Sleep symptoms and gastroesophageal reflux.
AB  - BACKGROUND: This study was to determine whether patients with significant
      nighttime heartburn had more disturbed sleep and more gastroesophageal acid
      reflux than those without significant nighttime heartburn. METHODS: Thirty-three
      reflux patients were stratified into 2 groups (nighttime heartburn, without
      nighttime heartburn). All patients completed questionnaires assessing daytime and
      nighttime heartburn and subjective sleep by Pittsburgh Sleep Quality Index. All
      participants underwent 24-hour esophageal pH monitoring and an overnight
      polysomnographic study. RESULTS: The number of reflux events longer than 5
      minutes was significantly greater in patients with nighttime heartburn than in
      those without nighttime heartburn for the total (P=0.004) and upright (P=0.01)
      position periods. Acid contact time was significantly greater in patients with
      nighttime heartburn during the upright (P=0.003) period and during the total
      (P=0.001) period. Patients with nighttime heartburn reported significantly
      greater subjective sleep impairment (8.1+/-0.7) than those without nighttime
      heartburn (6.1+/-0.4; P=0.02), but no difference could be observed in any
      objective sleep parameter by an overnight polysomnographic study between the
      groups. CONCLUSIONS: Patients with significant nighttime heartburn seem to have
      more acid reflux compared with those without nighttime heartburn. Nighttime
      heartburn together with sleep complaints is associated with excessive
      gastroesophageal reflux.

PMID- 18097284
TI  - Comparison between serology and histology in the diagnosis of advanced gastric
      body atrophy: a study in a Dutch primary community.
AB  - GOALS: To assess serologically diagnosed gastric body atrophy (GBA) by histology
      in a sample of the general population. BACKGROUND: GBA is a precursor lesion in
      gastric cancer. Data on GBA in a primary health care community in the Netherlands
      have not been reported. STUDY: Thirty-four subjects of 997 consecutive adults
      from a Dutch family practice had serologic GBA, according to hypergastrinemia
      (>100 ng/L), hypopepsinogenemia A (<17 microg/L), and a low pepsinogen A/C ratio
      (<1.6). Two years later, 25 subjects of this group, agreed in serologic retesting
      and gastroscopy with biopsies for histologic assessment according to the Sydney
      system. RESULTS: At serologic retesting, 20 of 25 subjects again fulfilled the
      serologic criteria of GBA. Histologic examination of the corpus biopsies showed
      advanced GBA in 18 subjects (75%) of 24 (1 subject had no corpus biopsies) and 17
      of 19 (89%) subjects with repeated positive serology. After disclosure of
      serology results, reexamination of the biopsies revealed GBA also in the 2
      patients with initially insufficient evidence of GBA, giving a concordance of
      100% (19/19). One subject with normal serum gastrin at retesting had both antral
      and body atrophy giving a concordance between serologic and histologic GBA of 95%
      (19/20). No adenomatous polyps, tumors, or dysplastic alterations were found.
      CONCLUSIONS: Identification by serology of asymptomatic patients with advanced
      GBA in primary care is adequately possible and useful in selecting for endoscopy.

PMID- 18097285
TI  - Reduced expression of sulfatides and galactosylceramide 3'-sulfotransferase in
      the gastric mucosa of chronic gastritis.
AB  - BACKGROUND: Sulfatides highly expressed in the normal gastric mucosa play
      important roles in gastric mucosal protection. However, it is unknown whether the
      sulfatides expression changes in chronic gastritis. METHODS: Sulfatides
      expression levels were examined with immunohistochemical staining in 77 specimens
      obtained from resected human stomachs, followed by the measurement of optical
      density of the staining under digital microscopy. For mRNA expression analysis of
      GalCer (galactosylceramide)-sulfotransferase and arylsulfatase A using a
      quantitative real time reverse transcription-polymerase chain reaction, 64 biopsy
      specimens were endoscopically taken from the gastric corpus of out patients.
      Mucosal changes were scored under microscopic observations according to the
      updated Sydney System classification. RESULTS: The sulfatides expression
      decreased along with the progression of mucosal atrophy and lymphocytes
      infiltration, and was barely observed in intestinal metaplasia. The mRNA
      expression of GalCer-sulfotransferase, a biosynthetic enzyme for sulfatides, also
      decreased along with the progression of mucosal atrophy and lymphocytes
      infiltration. In contrast, mRNA expression of arylsulfatase A, which degrades
      sulfatides, was not altered. CONCLUSIONS: Expression of sulfatides and GalCer
      sulfotransferase in the gastric mucosa of chronic gastritis is selectively
      reduced according to the mucosal atrophy and inflammation. Decreased expression
      of sulfatides may attribute to the deterioration of mucosal protection in chronic
      gastritis.

PMID- 18097286
TI  - Effects of Helicobacter pylori Infection on gastric mucin expression.
AB  - AIMS: This study was performed to determine the gastric distributions of MUC5AC
      and MUC6 depending on Helicobacter pylori (H. pylori) infection, and to evaluate
      whether the expressions of MUC5 and MUC6 change in H. pylori-associated
      gastroduodenal diseases. In addition, MUC5AC and MUC6 expressional changes were
      investigated before and after H. pylori eradication. METHODS: In the 224
      individuals (136 H. pylori-positive and 88 H. pylori-negative) who came from
      control (N=48), duodenal ulcer (N=35), benign gastric ulcer (N=61), dysplasia
      plus stomach cancer (N=80) groups, MUC5AC and MUC6 expressions were determined by
      immunohistochemical staining in the antrum and body, respectively. This staining
      for MUC5AC and MUC6 were reperformed in 113 of the 136 H. pylori-positive
      patients after successful H. pylori eradication by proton pump inhibitor-based
      triple therapy. RESULTS: (1) No difference was found between the H. pylori
      positive and negative groups in terms of MUC5AC expression. In contrast, MUC6
      expression was significantly lower in the H. pylori-positive group than in the H.
      pylori-negative group in the gastric body. Moreover, reduced MUC6 expression
      increased to the H. pylori-negative level after eradication. (2) Expressions of
      MUC5AC and MUC6 were significantly lower in the dysplasia plus cancer group than
      those of control in case of H. pylori positive. Similarly, MUC5AC and MUC6
      expressions were significantly lower in the presence of atrophic gastritis with
      intestinal metaplasia in case of H. pylori positive. (3) Aberrant expressions of
      MUC6 in foveolar cells were observed in both antrum (11.3%) and body (5.3%) only
      in the H. pylori-positive group, but this reverted to normal after H. pylori
      eradication. CONCLUSION: These results suggest that H. pylori infection causes
      alterations of mucin expression, closely related with the development of gastric
      atrophy with intestinal metaplasia, probably contributing to carcinogenesis.

PMID- 18097287
TI  - Higher gastric mucin secretion and lower gastric acid output in first-degree
      relatives of gastric cancer patients.
AB  - BACKGROUND: Patients infected by Helicobacter pylori who have first-degree
      relatives with gastric cancer have an 8-fold increased risk of developing gastric
      cancer themselves. Mucins are high-molecular-weight glycoproteins that play a
      cardinal role in the protective mechanism of the gastric epithelium. AIM: To
      study gastric acid and mucin secretion in dyspeptic patients with and without a
      family history of gastric cancer and H. pylori infection. MATERIALS AND METHODS:
      Twenty-six dyspeptic patients underwent esophago-gastro-duodenoscopy, gastric
      biopsies, and acid and mucin secretory tests. The sample was divided by family
      history of gastric cancer and H. pylori status. RESULTS: Patients who were
      infected by H. pylori had a significantly higher degree of inflammation than
      those who were not. H. pylori-positive patients with a positive family history
      had a lower basal and maximal gastric acid output than infected patients with no
      family history and noninfected controls, and a higher basal and maximal mucin
      output than infected patients with no family history. MUC5AC was the major mucin
      species expressed in gastric juice. CONCLUSIONS: In patients with relatives with
      gastric cancer, H. pylori infection is associated with a more severe inflammatory
      reaction consisting of decreased gastric acid secretion and increased mucin
      secretion.

PMID- 18097288
TI  - Endoscopic submucosal dissection for early gastric cancers: experience from a new
      endoscopic center in Taiwan.
AB  - GOAL: To evaluate the efficacy of endoscopic submucosal dissection (ESD) for
      early gastric cancers (EGCs) at a new endoscopic center. BACKGROUND: ESD is a
      novel technique that can facilitate en-bloc resection of EGCs, but seldom
      reported outside Japan. STUDY: A total of 25 consecutive patients (25 lesions)
      underwent ESD from June 2004 to March 2006. Patients were divided into 2 groups:
      group A underwent ESD from June 2004 to May 2005 (introduction stage) and group B
      from June 2005 to March 2006. The following data were obtained: tumor size, tumor
      location, operative time, and major complication. RESULTS: The complete resection
      was achieved in 20 lesions (success rate 80%). Four out of 10 lesions from group
      A were removed by conventional endoscopic mucosal resection (EMR) piecemeally
      after ESD failure. Conversely, 14 patients from group B (n=15) were resected by
      ESD en-bloc (success rate 93.3%). One patient with microscopic residual tumor
      after ESD was further treated by surgical resection. The time required for
      resection was significantly longer in group A when compared with group B (130.5
      min vs. 81.5 min, P<0.05). Postoperative complication rate between the 2 groups
      were similar. One patient with piecemeal EMR recurred in follow-up, and was
      further treated successfully by EMR. CONCLUSIONS: ESD is an ideal method for EGC
      treatment, but it may result in a risk of complication. The complete resection
      rate can be improved by endoscopist's experience. Sophisticated endoscopic
      hemostasis and clipping skills are essential prior ESD procedures. Conventional
      EMR techniques are also obligatory during the beginning period.

PMID- 18097289
TI  - A pilot study to evaluate the safety, tolerance, and efficacy of a novel
      stationary antral balloon (SAB) for obesity.
AB  - BACKGROUND: A 150 cm pear-shaped gastric balloon with a 30 cm-long duodenal stem
      and a 7 g metallic weight at its distal end was designed and developed to
      facilitate weight loss by (a) delaying gastric emptying thus enhancing
      interprandial satiety, and (b) stimulating antral and duodenal receptors of
      satiation. METHODS: Twenty-six patients (body mass index of 29 to 40 kg/m) who
      failed to lose weight despite dietary intervention underwent endoscopic
      implantation of the balloon device. Patients were monitored for tolerance to the
      balloon, complications, weight loss, and compliance with a restricted caloric
      intake. RESULTS: Six men and 20 women with a median body weight of 93.0 kg
      (range, 73.5 to 119.9), median body mass index 34.3 kg/m (range, 28.8 to 39.5)
      underwent balloon implantation for a median period of 4.0 months (range, 0.75 to
      6.0). Twenty-two patients successfully complied with a 1250 to 1500 kcal daily
      diet restriction during the study period. Median weight reduction was 6.5 kg
      (range, 3.7 to 19.9). Patients with initial body weight of >90 kg tended to loose
      more weight (8.1 kg) than patients weighing <90 kg (4.5 kg) (P=0.14). Nine
      patients with dwell times of 6 months lost 11.5+/-4.6 kg. The balloon
      malfunctioned in 4 patients (in 1 patient, the balloon leaked spontaneously but
      remained in the stomach and in 3 patients, the balloon migrated distally).
      CONCLUSIONS: Our novel balloon device may be effective in inducing weight loss by
      promoting compliance with a restricted caloric intake and is well tolerated due
      to its small size. Complications resulted from balloon rupture, which can be
      easily prevented by enhancements in design and use of alternative materials.

PMID- 18097290
TI  - Push enteroscopy in the era of capsule endoscopy.
AB  - GOALS: To evaluate the diagnostic yield of push enteroscopy in relation to
      indication and compare the yield in patients who had capsule endoscopy followed
      by push enteroscopy against capsule endoscopy naive patients. BACKGROUND: With
      the advent of capsule endoscopy the role of push enteroscopy needs to be
      reevaluated. STUDY: Patients who underwent push enteroscopy from January 2002 to
      May 2006 were included. RESULTS: One hundred fifty-five patients underwent push
      enteroscopy: 93 females, average age 55 years. There were 74 cases where both
      push enteroscopy (PE) and capsule endoscopy (CE) were performed. Indications for
      PE were iron deficiency anemia (n=51), overt bleeding (n=31), suspected celiac
      disease (n=32), refractory celiac disease (n=19), assessment for Crohn's disease
      (n=10), and miscellaneous (n=12). In 148 patients, an average length of 70 cm of
      small bowel was examined (range 30 to 130 cm). PE was unsuccessful in 7 patients
      due to anatomic strictures or patient distress. The overall diagnostic yield was
      30% with the highest yield in overt bleeding when compared with other subgroups
      (P<0.001). Nine percent of lesions were within the reach of a standard endoscope.
      Comparison of the diagnostic yield in patients who had CE followed by PE against
      CE naive patients was 41% versus 47%, respectively (P<1). There were no cases
      where push enteroscopy recognized a lesion that had not been already detected by
      capsule endoscopy. CONCLUSIONS: Push enteroscopy has the greatest diagnostic
      yield in patients with overt bleeding when compared with other referral
      indications. PE should be used as an adjuvant to CE for therapeutic intervention.

PMID- 18097291
TI  - Celiac disease diagnosed in the elderly.
AB  - BACKGROUND AND AIMS: In the past 20 years, a growing proportion of new cases of
      celiac disease (CD) are diagnosed in adults and in patients with extraintestinal
      manifestations. Our understanding of the extremely wide spectra of manifestations
      and the profound effects on elderly patients is improving. Nevertheless, CD is
      still underdiagnosed in elderly patients. In this study, we describe a case
      series of CD patients diagnosed after the age of 60. METHODS: A retrospective
      chart review was preformed in cases of CD diagnosed after the age of 60. Patients
      were included if they had positive serology and histologic findings compatible
      with CD. Eligible patients were reinterviewed, and demographic, clinical, and
      laboratory information were recorded. RESULTS: During the study period, 7
      patients with CD diagnosed after the age of 60 were identified. The most common
      presenting findings were weight loss, iron deficiency anemia, and diarrhea. Two
      patients suffered from severe early osteoperosis and 2 additional patients had
      elevated liver function tests. Neurologic manifestation was suspected in 3 cases.
      Two female patients presented with cognitive decline that was attributed to
      Alzheimer dementia but ameliorated after the initiation of gluten-free diet. The
      third patient had peripheral neuropathy that completely resolved after the
      initiation of gluten-free diet. Median lag in diagnosis was 8 years. Diet
      treatment led to complete resolution of symptoms in most cases and a significant
      weight gain (median 7.75 kg, range 5 to 11). One patient developed a fatal
      intestinal T-cell lymphoma. CONCLUSIONS: In this case series, we have described
      several cases of CD in patients over the age of 60 with a varied spectrum of
      manifestations. We have also found a significant lag in diagnosis and treatment.
      We believe that it is important to promote the identification of CD as a possible
      culprit in varied clinical conditions in the elderly population.

PMID- 18097292
TI  - A tale of two cities: typical celiac sprue presenting symptoms are significantly
      more common in Turkish than in US Patients.
AB  - GOAL: Recent studies suggest an increasing prevalence of atypical initial
      symptoms in patients with celiac disease (CD). The aim of this study was to
      compare the presenting symptoms of CD at 2 comparable referral institutions in
      South Florida, and in Ankara, Turkey. We retrospectively reviewed the records of
      patients with an initial diagnosis of CD by small bowel biopsy during the same
      (1991 to 2001) 10-year period at Cleveland Clinic Florida and University of
      Ankara, Turkey. A numerical score was assigned to presenting symptom and signs.
      RESULTS: There were 28 patients in the South Florida group (51% men) and 40
      patients in the Turkish group (35% men) (P=NS). The Turkish patients were
      significantly younger at diagnosis (36+/-2 y vs. US patients 66+/-3 y)
      (P<0.0001). Typical celiac symptom scores were similar (Turkey 1.1+/-0.2 vs.
      South Florida 1.3+/-0.3) (P=NS). Atypical symptom scores were significantly
      higher in the US patients (1.9+/-0.2) versus those from Turkey (1.2+/-0.1)
      (P<0.01). The Turkish patients were significantly more likely (P<0.01) to present
      with chronic diarrhea, hypoalbuminemia, and mactocytosis at the time of
      diagnosis. CONCLUSIONS: Although retrospective, this study points to striking
      differences in the clinical presentation of CD in individuals in South Florida,
      United States, and Ankara, Turkey, diagnosed during the same time period at both
      institutions. Turkish patients were younger, and more likely to present with
      chronic diarrhea, hypoalbuminemia, and microcytosis-as was more commonly seen in
      the United States in the 1960s and 70s. These findings raise the question of an
      interplay of demographics with diet and genetics in the presenting symptoms of CD
      in these 2 distant geographic areas.

PMID- 18097293
TI  - OctreoScan positive Crohn's disease mimicking an ileal carcinoid tumor.
AB  - Somatostatin receptors have been identified in many tissues throughout the human
      body. Alterations in the expression of somatostatin receptors have been reported
      in many disease states including both tumorous and nontumorous conditions.
      Somatostatin receptor scintigraphy utilizing OctreoScan (Mallinckrodt Medical,
      Inc., St. Louis, MO), a radiolabled form of octreotide, has been reported to be a
      highly sensitive imaging technique for identifying pathology, such as
      neuroendocrine tumors, that are somatostatin receptor dense. Unfortunately, many
      conditions cause an increase in the quantity of somatostatin receptors and
      therefore may cause false positive Octreoscans. In this report, we discuss the
      alterations in somatostatin receptors that occur with Crohn's disease and
      describe a case of an OctreoScan-positive inflammatory mass mimicking a carcinoid
      tumor.

PMID- 18097294
TI  - The involvement of the liver in systemic diseases.
AB  - The liver has a double blood supply and plays a central role in the metabolism of
      proteins, carbohydrates, and many medications. In addition, it has a role in the
      induction of immune tolerance and may also be a target for immune-mediated
      damage. For these reasons, the liver may be involved in many systemic diseases.
      In this review, we discuss the involvement of the liver in granulomatous,
      rheumatologic, malignant, and circulatory diseases. An understanding of the wide
      spectrum of liver involvement in systemic diseases will aid in both diagnosis and
      treatment of patients with a wide range of medical conditions.

PMID- 18097295
TI  - Efficacy of endoscopic ultrasound in characterizing mass lesions in chronic
      pancreatitis.
AB  - BACKGROUND AND GOALS: The aim of this study is to determine the influence of
      endoscopic ultrasound (EUS) in the detection of chronic pancreatitis and
      identification of pancreatic masses suspected by other radiographic imaging
      modalities in such a clinical background. METHODS: Retrospective analysis was
      performed on 105 consecutive pancreatic EUS examinations in an 18-month period at
      a single tertiary care referral center. Analysis included 75 patients with a
      suspected pancreatic mass by computerized axial tomography, magnetic resonance
      imaging, ultrasound, or endoscopic retrograde cholangiopancreotography. All
      patients underwent EUS examination and if a mass was visualized, fine-needle
      aspiration biopsy was performed. Patients underwent either surgical exploration
      or clinical and radiographic follow-up for 6 months to confirm EUS findings.
      RESULTS: Chronic pancreatitis was suspected in 53 individuals by clinical or
      radiographic methods. Using standard EUS parenchymal and ductal criteria, chronic
      pancreatitis was confirmed in 41 (77%) of patients. In 33 patients with chronic
      pancreatitis detected by EUS, initial referral was for pancreatic mass. Twenty
      eight (85%) patients had an actual mass and the remainder were false-positive
      clinical findings. Thirty-two percent of pancreatic masses in chronic
      pancreatitis were found to be malignant adenocarcinoma and the rest were
      inflammatory in nature. Subset analysis showed EUS-fine-needle aspiration of
      solid lesions to have a sensitivity and specificity of 87.9% and 100%,
      respectively. Detection of cystic lesions had a sensitivity and specificity of
      88.5% and 100%, respectively. CONCLUSIONS: EUS is superior to other radiographic
      modalities in the determination of chronic pancreatitis and detection of mass
      lesions.

PMID- 18097296
TI  - Survival and prognostic factors of unresectable pancreatic cancer.
AB  - GOALS: The aim of this study was to evaluate the prognostic significance of
      clinical and laboratory variables, and to investigate survival benefits for
      different treatment modalities in unresectable pancreatic cancer. BACKGROUND: The
      majority of pancreatic cancers are found to be unresectable. Therefore,
      estimations of prognosis and decisions of treatment modalities are important in
      optimizing the various aspects of care. STUDY: Three hundred and forty
      unresectable locally advanced, or metastatic pancreatic cancer patients were
      enrolled from January 1998 to January 2005 at the Seoul National University
      Hospital. RESULTS: One hundred and five patients received chemotherapy only and
      59 patients received concurrent chemoradiotherapy (CCRT). Age, performance
      status, tumor location, initial CA 19-9 level, American Joint Committee on Cancer
      stage, and treatment modality (supportive care only, chemotherapy, vs. CCRT) were
      found to have prognostic significance for overall survival (OS) by univariate
      analysis, whereas initial CA 19-9 level, stage, and treatment modality were
      identified as independent prognostic factors by multivariate analysis. In
      subgroup analysis, stage III patients treated by CCRT (median OS, 10.4 mo) or
      chemotherapy alone (11.3 mo) showed survival benefit over supportive care (6.4
      mo), and stage IV patients treated by chemotherapy alone (6.4 mo) showed survival
      benefit over supportive care (3.1 mo). CONCLUSIONS: Initial CA 19-9, American
      Joint Committee on Cancer stage, and treatment modality were independent
      prognostic factors of OS, and the patients who received chemotherapy or CCRT
      showed better survival than those who received supportive care only.

PMID- 18097297
TI  - Impaired anger control as an underappreciated side effect of treatments for
      chronic HCV infection in HIV-HCV coinfected patients.
AB  - OBJECTIVE: To study the specific impact of treatments for chronic hepatitis C
      virus (HCV) infection on anger expression and control in adult patients
      coinfected with HIV and HCV receiving antiretroviral therapy. DESIGN: In 2005, a
      cross-sectional survey, collecting both clinical and sociobehavioral data, was
      conducted in 2 French clinical centers among adult patients coinfected with HIV
      and HCV. METHODS: Participants were asked to answer anonymously a self
      administered questionnaire aimed at obtaining sociodemographic, clinical and
      behavioral characteristics including self-reported treatments' side effects,
      quality of life (WHOQOL-HIV BREF), and irritability and anger (STAXI-2). Clinical
      characteristics were obtained from medical records. RESULTS: Among the 139
      patients who were receiving antiretroviral therapy at the time of survey and who
      had complete self-reported data, 24 were being treated for their HCV infection,
      using either pegylated interferon and ribavirin or pegylated interferon alone.
      Control of anger was significantly lower among treated patients than among
      untreated ones (STAXI-2 anger control-out dimension median scores of 18.5 vs. 23
      respectively, P=0.02). Sociodemographic and clinical characteristics did not
      differ significantly between these 2 groups. Control of angry feelings was
      significantly correlated with psychologic and social relationship dimensions of
      quality of life. CONCLUSIONS: Treatment of HCV-HIV coinfected patients may
      require closer monitoring for anger control issues and adjustment of treatment as
      appropriate.

PMID- 18097298
TI  - Outcomes of a Hepatitis C screening program at a large urban VA medical center.
AB  - GOALS: To determine the outcomes of implementing clinical care guidelines for
      Hepatitis C screening, evaluation, and treatment in a large urban Veterans
      Affairs Medical Center. BACKGROUND: Little information exists regarding the
      actual outcomes of institutional screening programs for Hepatitis C. STUDY:
      Retrospective review of all patients tested for Hepatitis C at the Minneapolis
      Veterans Affairs Medical Center from January 1, 2000 to December 31, 2001.
      Logistic regression was used to determine factors related to successful referral
      and treatment. RESULTS: During this period 36,422 unique patients were screened
      for Hepatitis C virus (HCV) risk factors, resulting in 12,485 HCV enzyme-linked
      immunoassay antibody tests. HCV antibodies were positive in 681 (5.4%) patients
      and 520 (4.2%) were HCV-RNA-positive. Of HCV-RNA-positive patients, 430 (83%)
      were referred, 382 (73%) attended the Hepatitis clinic, and 232 (44.6%) received
      liver biopsies. Patients referred had significantly fewer comorbidities, known
      marital status, and greater prior clinic attendance than those not referred.
      Overall, 124 patients with established fibrosis received antiviral therapy (32%
      of patients attending clinic or 24% of viremic cohort). White race, fewer major
      medical problems, and age less than 60 years predicted antiviral treatment.
      Sustained virologic response occurred in 46 (37%) of treated patients (9% of the
      viremic cohort). Patients with a sustained virologic response include 17 patients
      with stage 3 to 4 fibrosis. CONCLUSIONS: This screening and referral program
      resulted in 73% of HCV-RNA-positive patients attending a specialty Hepatitis C
      clinic and 24% of those most likely to benefit received antiviral therapy.
      Measures to increase referral, engagement in care, and antiviral treatment are
      needed.

PMID- 18097299
TI  - Nonalcoholic fatty liver disease induced by leuprorelin acetate.
AB  - Leuprorelin acetate is an agonist of gonadotropin-releasing hormone, used as a
      first choice treatment in patients with prostate carcinoma. The impact of
      leuprorelin therapy in liver function and metabolism is largely unknown. We
      report about a patient who had been treated for 32 months with leuprorelin
      acetate, who developed a nonalcoholic fatty liver disease (NAFLD), associated
      with a focal lesion at the IV hepatic segment where histologic features appeared
      to be more severe. The patient, in addition to NAFLD, presented a marked
      iatrogenic hypotestosteronemia and full-criteria meeting the diagnosis of
      metabolic syndrome, including insulin resistance. The radiologic and clinical
      findings, the histopathologic features, and the absence of any hepatic
      abnormalities before treatment, support a causal role of leuprorelin in inducing
      metabolic derangement that, most likely secondary to androgen-deprivation, were,
      in turn, responsible for the development of NAFLD. In conclusion, this is the
      first case report of NAFLD with focal fatty liver associated with leuprorelin
      therapy. Patients in leuprorelin should be carefully monitored for the
      development of liver disease.

PMID- 18097300
TI  - Transient ischemic colitis after a pit viper bite (Agkistrodon blomhoffii
      brevicaudus).

PMID- 18097301
TI  - Thyrotoxic periodic paralysis induced by pegylated interferon alpha plus
      ribavirin for chronic hepatitis C.

PMID- 18097302
TI  - Addiction: the dark side of learning.

PMID- 18097303
TI  - Endoscopic dilation of benign esophageal strictures in a surgical unit: a report
      on 95 cases.
AB  - Ninety-five patients were treated by endoscopic dilation without fluoroscopic
      guidance between 1997 and 2005 for benign esophageal strictures. The etiologies
      were: anastomotic (38), postfundoplication (13), caustic (14), peptic (11),
      radiation-induced (10) and others (9). The strictures were classified at every
      session on a 0 to 4 scale on the basis of the diet and the luminal diameter.
      Savary-Gillard or Through-the Scope balloon dilators were used depending on the
      type and the location of the stenosis. A total of 472 dilation sessions were
      carried out without serious complications. A normal and a semisolid diet were
      respectively achieved in 75% and 91%. Recurrence of dysphagia was found in 33%
      and 51% of the patients respectively after 2 months and 1 year. Improvement of
      dysphagia, the number of sessions, and recurrence were significantly better in
      the patients with postsurgical stenosis as compared with those affected by
      caustic, peptic, and radiation-induced strictures.

PMID- 18097304
TI  - Laparoscopic surgery for symptomatic cholelithiasis during pregnancy.
AB  - INTRODUCTION: We are introducing here additional evidence regarding efficacy and
      safety of laparoscopic cholecystectomy during pregnancy. This is achieved by
      analysis of 10 successful cases of symptomatic cholelithiasis operated
      laparoscopically during pregnancy. PURPOSE: To prove the fact that laparoscopic
      cholecystectomy is safe and effective during pregnancy, especially in the first
      trimester. BACKGROUND: Cholecystectomy represents the second most common
      nonobstetric operation during pregnancy. The laparoscopic management of
      symptomatic cholelithiasis during pregnancy is becoming the standard of care at
      our center king Abdullah university hospital (KAUH). Old restrictions on this
      treatment modality are changing; open surgery is not considered to be the only
      choice any more. METHODS: Ten laparoscopic cholecystectomies during pregnancy at
      variable gestational ages performed between February 2002 and June 2006 are
      reported here, all at KAUH. Their medical records were reviewed, deliveries were
      followed up, outcomes were analyzed, and results were compared with literature.
      RESULTS: Five patients were in their first trimester; 3 were in their second
      trimester and 2 in their third trimester in my series. Open cholecystectomy was
      not used at all in these patients. Intraoperative cholangiography was not
      performed. No tocolytic agents were given. No maternal or fetal mortality have
      been reported. None of fetuses had anomalies. One patient who refused any
      surgical intervention presented with repeated attacks of biliary colic at
      gestational age of 26 weeks; this pregnancy ended up with stillbirth at 33 weeks.
      CONCLUSIONS: In my series, laparoscopic cholecystectomy was safe through out all
      stages of pregnancy. When undertaken by skilled laparoscopic surgeon, it carries
      low mortality and morbidity. We highlight the fact that first trimester
      symptomatic cholelithiasis can be managed safely by laparoscope. We add to the
      evidence that laparoscopic cholecystectomy may not interfere with organogenesis.
      Early uterine contractions were not reported, though, we think that prophylactic
      tocolytics are not indicated unless uterine contractions are confirmed. Certain
      positioning styles, and cannulation techniques, are part of major guidelines that
      we recommend to be followed during this surgery.

PMID- 18097305
TI  - Minimal access surgery for adult intussusception with subacute intestinal
      obstruction: a single center's decade-long experience.
AB  - INTRODUCTION: In adults, 1% to 5% of bowel obstruction is caused by
      intussusception. In adult intussusception, there will be a demonstrable cause in
      90% of cases, acting as the lead point. Laparoscopy is becoming more and more
      popular in its management. We present our series of intussusception in adults
      managed laparoscopically. MATERIALS AND METHODS: Between 1996 and 2006, we have
      treated 12 adults with intussusception who presented with acute or subacute
      intestinal obstruction. Computed tomographic scan confirmed the diagnosis in all
      cases. Laparoscopic-assisted resection with primary anastomosis was successfully
      performed for all cases. RESULTS: Males were more common, average being 38 years.
      Two patients had colonic carcinoma, as the leading point and the rest were benign
      tumors. There were no conversions or anastomotic leaks in any patient.
      DISCUSSION: The basic principles of surgery involve straightening or removing the
      involved section of bowel. The outcome of surgery depends on the stage of the
      intussusception at diagnosis and the underlying cause. If no underlying cause is
      found in these cases, no specific treatment is required. With early treatment,
      the outcome is generally excellent. CONCLUSIONS: Laparoscopy is a valuable
      diagnostic and therapeutic tool in the management of adult intussusception. It
      provides all the benefits of minimal access surgery.

PMID- 18097306
TI  - Intraoperative enteroscopy in minimally invasive surgery.
AB  - PURPOSE: The purpose of this study was to assess the efficacy and safety of
      intraoperative enteroscopy (IOE) in patients undergoing minimally invasive
      surgery. METHODS: Twelve patients underwent minimally invasive surgery and IOE at
      Miyazaki University Hospital. Patients included 11 men and 1 woman. After
      extraction of the intestine via minilaparotomy, enterotomy was performed, and a
      sterilized enteroscope was inserted. RESULTS: Length of the skin incision was
      5.7+/-0.2 cm (mean+/-standard error). Length of the small intestine observed
      enteroscopically was 334+/-19 cm. Distance from the ligament of Treitz to the
      orally observed jejunum was 11.8+/-3.6 cm. In 5 of 9 patients with Crohn disease,
      additional lesions were found by IOE that were not found by preoperative
      examination. One additional tumor was found in 1 patient with ileal tumor.
      Postoperative complications occurred in 2 patients. CONCLUSION: IOE is
      efficacious in patients undergoing minimally invasive surgery.

PMID- 18097307
TI  - Comparison of conventional and laparoscopic Hartmann's procedure reversal.
AB  - PURPOSE: This study compares open Hartmann's procedure reversal (OHPR) and
      laparoscopic Hartmann's procedure reversal (LHPR) in patients first treated for
      peritonitis (Henchey III or IV). METHODS: Fourteen patients who underwent LHPR
      during a 2-year period were compared with 20 patients who had previously
      undergone an open procedure at the same institution. RESULTS: Conversion rate was
      14.28%. Operating time was shorter for the laparoscopic group [143 (90 to 240)
      vs. 180 (90 to 350) min, P<0.05]. Hospital length of stay was shorter for the
      laparoscopic group [9.5 (4 to 18) vs. 11 (6 to 39)]. Use of patient-controlled
      analgesia was not significantly shorter in the laparoscopic group [3 (0 to 4) vs.
      3.5 (0 to 8)]. Morbidities observed in the LHPR group include a parietal abscess
      and an anastomotic stenosis without surgical treatment. The OHPR group had 6
      complications: 1 anastomotic leak and 5 incisional hernias. CONCLUSIONS: LHPR
      with a conversion rate of 14.28% seems to be a method with shorter operating time
      and less morbidity compared with OHPR.

PMID- 18097308
TI  - Stapled hemorrhoidopexy: a technique for applying the crucial purse string suture
      (MAMC Technique).
AB  - BACKGROUND: Stapled hemorrhoidopexy for prolapsing hemorrhoids has been found to
      be associated with lesser postoperative pain and consequently earlier
      mobilization and return to work, in comparison to conventional hemorrhoidectomy.
      Purse string application remains a crucial step to ensure adequate lifting of the
      anal mucosa and this step is technically tedious in the presence of large
      hemorrhoids obscuring the vision using the standard purse string applicator. The
      proposed method in our technique makes this crucial step more reliable, easier,
      and safe in the hands of the beginner and the experienced surgeon alike. METHODS:
      Thirty healthy adults (21 males and 9 females) with grade 3 or 4 hemorrhoids
      underwent stapled hemorrhoidopexy at a large university referral hospital in New
      Delhi. Purse string application was the first step in the entire procedure even
      before the application of the circular anal dilator. The purse string was applied
      using authors' method herein after referred to as Maulana Azad Medical College
      "(MAMC) technique" after the name of the institution. Rest of the procedure was
      completed as described by Longo et al. RESULTS: The mean operative time was 26
      minutes (range 16 to 40 min). The mean visual analog scale (VAS) pain score on
      day 1 was 1.6 (range 0 to 3). The mean hospital stay was 1.1 days (range 1 to 2
      d). There was no major intraoperative complication and one case each of
      postoperative urinary retention and residual hemorrhoid, there was no recurrence,
      anal stenosis, or anal incontinence after a mean follow up of 15 months (range 3
      to 24 mo). CONCLUSIONS: The procedure described is safe, easy to learn, and
      technically sound, enabling the application of the crucial purse string at the
      desired distance from the dentate line, in the correct submucosal plane with
      closely placed bites and at the same transverse level.

PMID- 18097309
TI  - Adrenal masses in children: the role of minimally invasive surgery.
AB  - The development of laparoscopic surgery has extended its uses to include
      adrenalectomy in children and in adults. Because conventional adrenalectomy
      requires a large incision, minimally invasive surgery offers a less aggressive
      solution in some selected cases. Twenty-nine adrenal masses in 26 children were
      treated using adrenalectomy between 1994 and 2004 (12 were treated
      laparoscopically, the remaining 17 with open surgery). Minimally invasive
      procedures were limited to the removal of small localized adrenal tumors and to
      biopsies. Although this approach must be limited to operations on lesions
      presumed to be benign, preoperative criteria for nonmalignancy are often
      difficult to define. Indications can be expanded to include to stage I
      neuroblastoma. There seems to be no age and weight limit. The technique applied
      varies in accordance with anatomy and the surgeon's experience: minimally
      invasive adrenalectomy, in our experience, was preferentially performed through a
      lateral retroperitoneal approach. Laparoscopic adrenalectomy can be used if the
      selection of cases is rigorous and the operations are performed by well-trained
      laparoscopic surgeons.

PMID- 18097310
TI  - Anatomy of the Sacral Roots and the Pelvic Splanchnic Nerves in Women Using the
      LANN Technique.
AB  - AIMS: To report on our anatomic and electrophysiologic findings about the sacral
      nerve roots and the pelvic splanchnic nerves during laparoscopic pelvic surgery.
      METHODS: The pelvic splanchnic nerves and the sacral nerve roots were dissected
      in 336 consecutive patients undergoing laparoscopy for pelvic pain syndrome or
      gynecologic diseases. Intraoperative assessment of the functionality of the
      exposed nerves was performed using the LAparoscopic Neuro-Navigation (LANN)
      technique. RESULTS: Dissection of the sacral roots and the splanchnic pelvic
      nerves lateral to the sacral hypogastric fascia was feasible without any
      complications in all patients in this series. The mean surgical time was 16
      minutes per side. The pelvic splanchnic nerves could be divided anatomically and
      functionally into vesical and rectal nerve fibers. CONCLUSIONS: Laparoscopy in
      combination with the LANN technique not only permits an intraoperative functional
      mapping of the pelvic motoric autonomous nerves but also a differentiation
      between the vesical and rectal nerves and between the efferent and afferent
      pelvic nerves.

PMID- 18097311
TI  - Evaluation of compensatory sweating after bilateral thoracoscopic sympathectomy
      for palmar hyperhidrosis.
AB  - The study is a retrospective review of 60 patients undergoing bilateral T2-T3
      thoracoscopic sympathectomy for palmar hyperhidrosis in our department between
      1997 and 2003. The study was based on a telephone questionnaire and medical chart
      review. Forty patients (67%) replied to the questionnaire and were included in
      the study. Postoperative complications, therapeutic results, patient
      satisfaction, and the severity of compensatory sweating (CS) were assessed. In
      all patients both palms were dry at the end of surgery. Postoperative
      complications included permanent unilateral Horner syndrome, wound infection, and
      residual pneumothorax resolving after thoracal drainage, in one patient each. CS
      with different severity occurred in 35 patients (87.5%). Six patients (15%)
      regretted undergoing the operation due to the extent and severity of the CS
      seriously affecting their quality of life. Thoracoscopic sympathectomy is a
      simple procedure with a high success rate. However, CS is a serious complication
      and a significant number of patients may regret undergoing the operation; a
      careful selection of patients and comprehensive explanation are advisable.

PMID- 18097312
TI  - Removal of transabdominal sutures for chronic pain after laparoscopic ventral and
      incisional hernia repair.
AB  - Some patients who have undergone laparoscopic repair of ventral and incisional
      hernia have persistent postoperative pain, assumed to be caused by the presence
      of transabdominal sutures (TAS). We investigated whether removal of these sutures
      relieves discomfort. Of 375 patients who underwent laparoscopic repair of ventral
      and incisional hernia, 6 patients (1.6%) had persistent pain resistant to
      conservative therapy. These patients underwent relaparoscopy and removal of TAS
      at all apparent pain sites. Postoperatively, 3 patients had complete pain relief.
      Two patients had some improvement but moderate, less localized, pain remained.
      The sixth patient experienced no change at all. Removal of TAS deemed responsible
      for pain may occasionally provide relief, but the results of removal seem
      unpredictable and less effective than previously assumed.

PMID- 18097313
TI  - Laparoscopic duodenal switch for pathologic duodenogastric reflux: initial
      experience.
AB  - Duodenogastric reflux (DGR) is barely responsive to medications and antireflux
      fundoplication is not able to control the gastric symptoms. Duodenal switch (DS)
      preserves the physiologic food transit while creating an effective Roux-en-Y
      diversion to duodenal juice. However, it never enjoyed great popularity, perhaps
      due to the invasiveness of the open approach. The paper reports our initial
      experience with laparoscopic DS. Preoperative assessment, surgical technique, and
      outcomes are described. Normalization of DGR was demonstrated by preoperative and
      postoperative 24-hour bilimetry and pH-multichannel intraluminal impedance. The
      procedure was completed under laparoscopy in all the cases with a mean operative
      time of 165 minutes. Mean blood loss was 200 mL. No patient required admission to
      the intensive care unit. Initial experience with laparoscopic DS encourages
      continued use of the minimally invasive approach. A meticulous preoperative
      evaluation is essential to place a correct indication.

PMID- 18097314
TI  - Band ligation of the perforated gall bladder during laparoscopic cholecystectomy.
AB  - Perforation of the gall bladder is a frequent complication during laparoscopic
      cholecystectomy. Grasping the perforated part of the gall bladder, clip
      application, or endoscopic loop application are possible solutions to prevent
      spillage. We propose laparoscopic rubber band application to close the perforated
      part of the gall bladder as an easy and safe method. We performed rubber band
      application after iatrogenic perforation of the gall bladder during laparoscopic
      cholecystectomy in 5 patients. Two-millimeter-wide multiple rubber rings, cut
      from a 14-Fr Foley catheter, are loaded on a grasper. When a perforation occurred
      during the dissection of the gall bladder, the hole is grasped with this
      instrument and 1 of the rings is placed on the gall bladder by the aid of a
      dissector. Thus, the grasper remained available for traction of the Hartmann's
      pouch during further dissection of the gall bladder. The rubber bands were placed
      successfully in all cases. Two perforations occurred in 1 case, and 2 bands were
      placed with ease. Bile leakage or gall stone spillage did not occur. Operation
      time was not prolonged. Rubber band ligation of perforation of the gall bladder
      is a simple, safe, inexpensive, and effective method to prevent spillage of the
      bile or gallstones in laparoscopic surgery.

PMID- 18097315
TI  - Suture damage during robot-assisted vascular surgery: is it an issue?
AB  - BACKGROUND: Manipulation of sutures during endoscopic surgery could lead to
      damage of suture structure, supposedly resulting in loss of strength. Lack of
      tactile feedback in robotic surgical systems might increase this problem. The
      objective of this study is to evaluate suture strength after robotic manipulation
      and to determine which suture material is least susceptible to damage from
      robotic manipulation. METHODS: The da Vinci surgical system was used to
      manipulate sutures. Three different suture materials (Prolene, ePTFE, Ethibond)
      of 3 different sizes (3-0, 4-0, and 5-0) were tested. A total of 270 sutures were
      pulled on a Servohydraulic Universal Testing Machine. The frequency of breaks at
      a manipulation-point and the maximum applied force (N) before the suture broke
      were used for statistic analysis. RESULTS: No loss in strength was shown in the
      ePTFE sutures after manipulation, whereas both Prolene and Ethibond sutures
      showed a significant loss of strength. CONCLUSIONS: ePTFE sutures are least
      susceptible to robotic manipulations and are, therefore, to be considered as a
      material of first choice.

PMID- 18097316
TI  - Laparoscopic retrieval of "stubborn" foreign bodies in the foregut: a case report
      and literature survey.
AB  - INTRODUCTION: Foreign bodies (FBs) are commonly seen in pediatric and
      gastroenterologist practice. Most of them will pass without intervention; those
      that do not will need surgery. Laparoscopy has been used to achieve this to good
      effect. We present a child with ingestion of multiple magnets. CASE REPORT: The
      patient was a 2-year-old child with history of ingestion of magnets. Laparoscopy
      was planned as endoscopic removal had failed. There were 3 magnets in the stomach
      and 1 in the jejunum and they were attached together, as if in a
      "gastrojejunostomy." Laparoscopic removal was performed successfully for the
      child. RESULTS: He had an uneventful postoperative recovery and was discharged on
      the third postoperative day. DISCUSSION: Coins are the most commonly ingested
      FBs. Multiple magnet ingestion poses a unique problem, as they are likely to
      stick together and cause pressure necrosis with fistula formation. Surgical
      intervention is necessary to prevent this potentially deadly complication.
      CONCLUSIONS: Laparoscopy has been found to be very useful in the removal of
      intraluminal FBs, especially when conservative measures fail. Prevention should
      be the main objective and parental involvement is crucial.

PMID- 18097317
TI  - A case of early depressed-type ampullary carcinoma treated by wire-guided
      endoscopic resection.
AB  - A 72-year-old man, with known prostate cancer, was admitted to our endoscopic
      unit for further evaluation of an obstruction at major papilla level. Endoscopic
      cholangiopancreatography revealed a depressed-type carcinoma at the ampulla of
      Vater and dilation of both the common bile and pancreatic ducts without
      intraductal filling defects. Intraductal ultrasonography showed a hypoechoic mass
      limited to the ampulla of Vater. Endoscopic wire-guided ampullectomy was
      performed after informed consent was obtained. Histologic examination of the
      resected specimen showed a completely excised well-differentiated adenocarcinoma
      limited to the ampulla of Vater. Both accurate preoperative staging and proper
      histologic evaluation of the resected specimen seem to justify endoscopic
      treatment of early ampullary cancer by an experienced endoscopist.

PMID- 18097318
TI  - A case of robot-assisted excision of choledochal cyst, hepaticojejunostomy, and
      extracorporeal Roux-en-y anastomosis using the da Vinci surgical system.
AB  - Choledochal cyst is a rare disease in the Western world, but a high incidence is
      noted in Asia. Complete cyst excision with Roux-en-y hepaticoenterostomy is the
      treatment of choice for choledochal cyst, which has been attempted
      laparoscopically with the advancement of laparoscopic experience. Recently, a
      telemanipulative robotic surgical system was introduced, providing instruments
      with wrist-type end-effectors and 3-dimensional visualization of the operative
      field. Herein, we present a case of robot-assisted correction of a choledochal
      cyst.

PMID- 18097319
TI  - Intra-abdominal actinomycosis 11 years after spilled gallstones at the time of
      laparoscopic cholecystectomy.
AB  - A 72-year-old woman with a remote surgical history of a laparoscopic
      cholecystectomy (LC) complicated by gallstone spillage presented with fever, 3
      weeks of nausea and anorexia, and increasing right upper quadrant abdominal pain.
      After the LC performed 11 years before symptom presentation, the patient was
      found to have a fluid collection in the right upper quadrant. The patient was
      asymptomatic at the time, and had no symptoms while being monitored with
      sequential scans over the next 5 years. At presentation, computed tomography
      scans revealed a subhepatic, lobulated fluid collection and a radioopacity,
      consistent with a gallstone, at the inferior aspect of the fluid collection.
      Subsequent percutaneous drainage of the fluid collection yielded pus that
      eventually grew Actinomyces israelii. Intravenous clindamycin therapy was
      initiated, and with further drainage, the abscess resolved. Intra-abdominal
      abscess formation can present as a delayed complication dropped stones during LC,
      but these cases usually present within a few years of the procedure. In this
      case, however, an intra-abdominal abscess formed 11 years after the LC. This
      extended duration from surgical manipulation to symptom onset is likely secondary
      to the indolent nature of the infecting organism, A. israelii.

PMID- 18097320
TI  - Advantages of fibrin glue spray in laparoscopic liver biopsies.
AB  - Fibrin glue has been shown to be a highly effective adjuvant in surgical repair.
      We present the case of a 14-year-old boy, who was operated on a right side
      abdominal neuroblastoma at the age of 4 years. The regular follow-up examinations
      later on were uneventful; however after 10 years, focal lesions were observed on
      the surface of the liver, which were confirmed by computer tomograms. To rule out
      further malignancy and histologically investigate the lesions, laparoscopic
      biopsy of the affected sites of the liver was performed. After obtaining the
      biopsy samples, the sites were sealed with fibrin glue using the special
      laparoscopic spray applicator head. The spray technique of sealing liver biopsy
      sites was found to be more effective and economical than the traditional
      technique of fibrin glue application. The advantages of spray application for
      parenchymatous organ intervention in the laparoscopic setting have been
      elaborated.

PMID- 18097321
TI  - Laparoscopic paracolostomy hernia mesh repair.
AB  - Paracolostomy hernia is a common occurrence, representing a late complication of
      stoma surgery. Different surgical techniques have been proposed to repair the
      wall defect, but the lowest recurrence rates are associated with the use of mesh.
      We present the case report of a patient in which laparoscopic paracolostomy
      hernia mesh repair has been successfully performed.

PMID- 18097322
TI  - Necrotizing fasciitis after laparoscopic colonic surgery: case report and review
      of the literature.
AB  - A 67-year-old woman, with a past medical history of diabetes mellitus and
      hypertension, underwent an elective laparoscopic anterior resection for sigmoid
      colon adenocarcinoma. She was readmitted on the tenth postoperative day with
      complaints of abdominal pain and a foul smelling discharge from her abdominal
      wound. She was later diagnosed with necrotizing fasciitis (NF) over the
      extraction wound. To our knowledge there has only been one other case of NF after
      laparoscopic colonic surgery reported in the literature. We reviewed the
      literature on NF after laparoscopic surgery, and discussed the clinical
      diagnosis; diagnostic adjuncts such as magnetic resonance imaging, bedside
      exploration under local anesthesia, frozen section of deep incisional biopsies,
      and laboratory tests; and management principles of NF. Although there is a low
      incidence of wound infections associated with laparoscopic colonic surgery,
      necrotizing infections although rare, are a very real possibility.

PMID- 18097323
TI  - Port site metastasis of B-cell lymphoma: a first occurrence or an underreported
      complication?
AB  - Minimally invasive techniques have been accepted as safe and reliable in the work
      up of patients with lymphoproliferative disorders. As the oncologic indications
      of laparoscopy expand, many authors have raised concerns regarding the occurrence
      of port site metastases after minimally invasive procedures for a multiform array
      of neoplastic diseases. A review of the existing literature demonstrates no
      mention of port site occurrence following staging laparoscopy for malignant
      hematologic disorders. We report the first case of port site metastasis after
      diagnostic laparoscopy in a patient with large B-cell lymphoma. As these
      procedures become more common, we may be exposed to the increasing numbers of
      patients with this clinical presentation. A clear knowledge of the technical
      steps to minimize risk of port site metastasis is mandatory for any advanced
      laparoscopic surgeon.

PMID- 18097324
TI  - Laparoscopic excision of intra-abdominal paragonimiasis.
AB  - Lung fluke, Paragonimus westermani of Paragonimus species usually are accompanied
      by a persistent cough, hemoptysis, and chest pain. Extrapulmonary paragonimiasis
      caused by ectopic parasites in aberrant locations such as the abdominal wall,
      abdominal organs, and brain has been reported and the most commonly involved
      extrapulmonary organ is the brain. We present a case of 56-year-old male patient
      with intra-abdominal paragonimiasis who underwent laparoscopic excision of
      abdominal granuloma caused by parasite infection. An intra-abdominal mass
      associated with eosinophilia might be related to parasite infection. A
      laparoscopic approach is the most appropriate treatment modality in such benign
      abdominal pathology.

PMID- 18097325
TI  - Intraoperative death due to thrombotic thrombocytopenic purpura (TTP)-related
      acute myocardial failure in a patient undergoing laparoscopic splenectomy.
AB  - Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder characterized
      by a pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal
      dysfunction, fever, and a fluctuating neurologic syndrome. Splenectomy is
      performed for patients who are refractory to plasma therapy and for relapsing
      TTP. We describe a case of a patient who died due to intramyocardial hemorrhage
      after undergoing laparoscopic splenectomy for TTP resistant to treatment with
      plasmapheresis. A 52-year-old woman was admitted with ecchymoses, low platelet
      count, weakness of left face and upper extremity, and a presumptive diagnosis of
      TTP. Vital signs were stable. White blood count was 7800/microL, hemoglobin 7.9
      g/dL, and platelet count of 13,000/microL. Her basic metabolic panel and liver
      function tests were normal. Further laboratory workup confirmed the diagnosis of
      TTP. The patient was initially treated with plasmapheresis and high dose steroid
      therapy but underwent an emergent laparoscopic splenectomy due to refractory TTP.
      At the end of the uneventful procedure, the patient suffered a cardiac arrest and
      died. Autopsy concluded that the death was from myocardial failure due to
      extensive myocardial hemorrhage secondary to TTP. There are several published
      case reports of sudden death due to cardiac involvement in TTP. However,
      intraoperative mortality is not reported. We conclude that TTP-related acute
      heart failure may represent an extremely important clinical risk in these
      patients who are undergoing surgery.

PMID- 18097326
TI  - Successful video-assisted thoracic surgery lobectomy in a single-lung patient.
AB  - In terms of perioperative management, it is extremely difficult to perform a
      video-assisted thoracic surgery lobectomy for primary lung cancer in patients
      previously undergoing a contralateral pneumonectomy. We herein describe the
      successful video-assisted thoracic surgery lobectomy with systematic mediastinal
      lymph node dissection in a single-lung patient with clinical stage IA nonsmall
      cell lung cancer. Our experience indicates surgeons may consider the procedure if
      the following conditions are met: (1) satisfactory pulmonary function, (2) the
      selective bronchial blockade of the lobe to be resected, and (3) the effective
      retraction of the inflated lung.

PMID- 18097327
TI  - Gasless laparoscopic surgery for ovarian cyst in a second trimester pregnant
      patient with a ventricular septal defect.
AB  - BACKGROUND: Ovarian cysts are estimated to occur in 4.1% of second trimester and
      third trimester obstetric ultrasonographic examination. Laparoscopy has not been
      widely performed during pregnancy, especially after the first trimester, and
      laparotomy remains the standard of care. Herein, we report a use of gasless
      laparoscopy in the management of an ovarian cyst during second trimester of
      pregnancy. CASE: A 21-year-old primigravida woman initially presented for
      antenatal care at 6 weeks' pregnancy. She had an underlying small subaortic
      ventricular septal wall defect with a functional class I. A left ovarian cyst was
      found during ultrasound examination. Elective gasless laparoscopic surgery due to
      persistence ovarian cyst was performed at 14th week of gestation without
      complications. The subsequent antenatal course was unremarkable. The pregnancy
      carried to term with uneventful maternal and fetal outcomes. CONCLUSIONS: Gasless
      laparoscopy is an alternative procedure for the management of ovarian cyst during
      pregnancy. This allows laparoscopic surgery that is minimally invasive for both
      the mother and the fetus.

PMID- 18097328
TI  - Stone formation on surgical staple in the bladder: a long-term complication of
      laparoscopic colposuspension.
AB  - We present a case of a bladder stone that developed around a surgical staple
      after laparoscopic colposuspension. The patient had undergone laparoscopic
      colposuspension for stress urinary incontinence at another institution 6 years
      ago. The hernia mesh and a tacker had been used as a surgical stapler. The stone
      and staple were retrieved endoscopically. To our knowledge, this is the first
      case of such a complication after laparoscopic colposuspension with a stapling
      device.

PMID- 18097329
TI  - Laparoscopic nephrectomy for xanthogranulomatous pyelonephritis in the absence of
      kidney stones or clinical urinary infection.
AB  - Here, we present a patient who underwent transperitoneal laparoscopic nephrectomy
      for a nonfunctional kidney on the left side, and who was found to have
      xanthogranulomatous pyelonephritis (XGP) on the subsequent histopathology
      examination. XGP is a severe, chronic infection of the renal parenchyma.
      Nephrectomy is the treatment of choice. Preoperative diagnosis of XGP can be
      challenging because the clinical presentation may vary. Our patient's loss of
      kidney function was due to a simple cortical kidney cyst that compressed the
      urinary collecting system. He presented only with mild flank pain and a poorly
      functioning kidney, and therefore XGP was not suspected before surgery. Because
      of the renal and perirenal inflammatory changes that commonly accompany XGP, the
      laparoscopic approach is difficult and is therefore rarely used. However,
      laparoscopic nephrectomy for XGP offers an easier recovery for the patient and
      therefore deserves further consideration as a method of treatment.

PMID- 18097330
TI  - Laparoscopic nephron-sparing surgery for metanephric adenoma.
AB  - A 47-year-old patient presented with hematuria of 3-month duration. Computed
      tomography revealed right lower polar exophytic mass. Laparoscopic nephron
      sparing surgery was performed. The macroscopic examination of the mass showed
      encapsulated tumor with soft pultaceous material. Histologic examination of the
      mass was consistent with metanephric adenoma. We are reporting this case of
      metanephric adenoma, being treated with laparoscopic partial nephrectomy.

PMID- 18097331
TI  - Reflux laryngitis: a feasible indication for laparoscopic antireflux surgery?

PMID- 18097333
TI  - Outcome and lack of prognostic factors in stapes surgery.
AB  - OBJECTIVE: To analyze predictive factors of outcome after primary stapes surgery
      for otosclerosis. STUDY DESIGN: Retrospective review of 139 patients with
      otosclerosis and 147 operations performed by the same senior surgeon with the
      same surgical technique. SETTING: Academic hospital and tertiary referral center.
      PATIENTS: All patients had documented preoperative and peroperative audiologic
      assessments and preoperative records. The mean age of patients was 44.31 years.
      INTERVENTION: Stapedotomy with diode laser using Teflon prosthesis. MAIN OUTCOME
      MEASURES: The bone conduction threshold changes, the improvement of pure-tone
      average air-bone gaps (PTA-ABGs), and ABGs for each frequency were analyzed using
      0.5, 1, 2, and 4 kHz. Success rate was defined by postoperative ABG. Log-rank
      test was used to define significant factors. RESULTS: At 24 hours postoperative,
      there was a significant deterioration in bone conduction threshold at 1, 2, and 4
      kHz. However, at 4 kHz, the threshold remained significantly worse at longer
      term. There was a significant improvement of the PTA-ABG. Eighty-six percent of
      patients obtained a PTA-ABG of 20 dB or less. We also obtained a significant ABG
      closure on every frequency except on 4 kHz. Multivariate statistical analysis had
      not identified a predictive factor of hearing outcomes such as the anatomy of the
      facial nerve, the incus, the stapes footplate and the external auditory canal,
      the prosthesis crimping, bleeding, and surgical damage of the tympanic membrane.
      CONCLUSION: In experienced hands, we observed a significantly transient
      depression of bone conduction hearing levels that was definitively present at 4
      kHz. Peroperative difficult or abnormal situations did not seem to have an
      influence on the hearing outcome. Those statements will enable accurate
      preoperative counseling. It will also permit precise matching of future series to
      allow accurate comparisons.

PMID- 18097334
TI  - Idiopathic inflammatory medial meatal fibrotizing otitis presenting in children.
AB  - OBJECTIVE: Acquired atresia of the ear canal presents rarely in children.
      Idiopathic inflammatory medial meatal fibrotizing otitis (IMFO) evidently has its
      own distinct etiopathologic findings causing acquired ear canal atresia.
      PATIENTS: Two IMFO children treated and followed-up at the Department of
      Otorhinolaryngology of Helsinki University Hospital. INTERVENTIONS: Clinical and
      radiologic evaluation of 2 children with IMFO solely affecting the glabrous skin
      over the osseous part of the ear canal and the tympanic membrane. MAIN OUTCOME
      MEASURE: Review of identical cases of the acquired postinflammatory or
      inflammatory medial meatal atresia in children reported in association with
      literature. RESULT: Idiopathic inflammatory medial meatal fibrotizing otitis,
      affecting solely the glabrous skin on the tympanic membrane and the osseous part
      of the external ear canals, is manifesting in 2 children without ongoing chronic
      middle ear infection. CONCLUSION: The etiopathologic findings or pathophysiology
      of IMFO is speculative. The success of surgical correction of the already-formed
      fibrous atresia has not been established.

PMID- 18097335
TI  - Long-term hearing outcomes after ossiculoplasty in comparison to short-term
      outcomes.
AB  - OBJECTIVES: To investigate long-term hearing outcomes after ossiculoplasty. STUDY
      DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: One
      hundred ninety-nine patients who underwent ossiculoplasty between 1989 and 2001
      by the same surgeon and were followed for more than 5 years. METHODS:
      Postoperative hearing outcomes were considered successful if the postoperative
      air-bone gap was within 20 dB. The outcomes after 6 months and 5 years were
      analyzed. RESULTS: The overall rate of successful outcomes was 61.3% after 6
      months and 54.3% after 5 years. There was a significant difference between 6
      months and 5 years (p < 0.05). The significant deterioration of long-term hearing
      outcomes was found in malleus-present ears, ears with cholesteatoma/atelectasis,
      adults, and ears treated by one-stage operation. The reasons for long-term
      unsuccessful outcomes were adhesion or retraction of the ear drum in 13 ears
      (54.2%). CONCLUSION: The hearing outcomes after ossiculoplasty showed significant
      deterioration on long-term follow-up. Innovative approaches to the management of
      cholesteatoma/atelectasis are necessary to improve and stabilize long-term
      hearing outcomes.

PMID- 18097336
TI  - Labyrinthitis related to Wegener granulomatosis: magnetic resonance imaging
      findings.

PMID- 18097337
TI  - [Molecular basis of diabetic retinopathy].
AB  - Civilization-related diseases are an increasingly frequent problem of ours times.
      Among these,eye diseases, including diabetic retinopathy, are found to be a very
      serious problem in chronic complications of diabetes mellitus. The mechanisms
      involved in susceptibility to and the progression of diabetic retinopathy remain
      unclear. Much evidence suggests that diabetic retinopathy may be associated with
      gene polymorphisms of factors involved in angiogenesis, including the VEGF, SDH,
      AR, SDF-1, and TIMP-3 genes. Especially polymorphisms of the promotor regions of
      the VEGF (634 C/G) and SDH (1214 C/G) genes might contribute to the development
      of diabetic retinopathy. It is believed that an understanding of the molecular
      basis of diabetic retinopathy might help in designing new therapeutic approaches
      for human treatment.

PMID- 18097338
TI  - [Current views on the mechanism of oncogenic cell transformation in ovine
      pulmonary adenocarcinoma].
AB  - Lung cancer is the most frequently diagnosed of all the human neoplasms leading
      to death. Because twenty percent of cases are not associated with cigarette
      smoking, other causes and methods of early diagnosis are being sought.
      Bronchioloalveolar cancer, which is a subtype of the most common primary lung
      cancer, adenocarcinoma, is very similar to ovine pulmonary adenocarcinoma (OPA),
      a naturally occurring lung cancer in sheep. OPA is caused by the virus Jaagsiekte
      Sheep Retrovirus (JSRV), a member of the genus of beta-retroviruses. The virus
      induces neoplastic transformation of secretory epithelial cells of the lung, i.e.
      alveolar type II pneumocytes and Clara cells. JSRV's tropism for these cells is
      connected with viral LTR regions interacting with cellular factors that play
      major roles in the expression of lung-specific genes, e.g. those of surfactant
      proteins. Results of studies on the mechanisms of viral mutagenesis indicate a
      viral envelope protein (Env) as an oncogenic factor. There are two main enzymatic
      pathways involved in the cell transformation: PI3K-Akt and Ras-MEK-MAPK, both
      activated by the cytoplasmic tail of the envelope protein. Tumor development is
      associated with telomerase activation. Insertional mutagenesis has also been
      suggested because there is at least one common integration site for JSRV in OPA.
      Morphological and histological similarities with human bronchioloalveolar cancer
      and the possibility of experimental induction of the tumor in animals makes OPA a
      good model for the study of oncogenesis and target therapy of lung
      adenocarcinoma.

PMID- 18097339
TI  - [Exopolysaccharides of lactic acid bacteria: structure and biosynthesis].
AB  - The group of lactic acid bacteria (LABs) includes four genera: Lactobacillus,
      Leuconostoc, Pediococcus, and Streptococcus. The most characteristic feature of
      this group of microorganisms is the production of lactic acid as a main product
      of carbohydrate metabolism. LABs are responsible for the fermentation of
      alimentary products and they also produce a variety of agents, among them
      exopolysaccharides (EPSs), which inhibit the growth of pathogenic bacteria. In
      this article on the different types of EPSs produced by LABs, data concerning
      their structure and biosynthesis are presented.

PMID- 18097340
TI  - [The role of oncogenic tyrosine kinases in the cellular response to anticancer
      therapy].
AB  - Oncogenic tyrosine kinases (OTKs) expressed in malignant tumors stimulate cell
      proliferation, inhibition of apoptosis, and drug resistance. There are at least
      three mechanisms of response to chemo- and radiotherapy in OTK-positive cells:
      overexpression of anti-apoptotic proteins (such as Bcl-xL and Bcl-2) and blocking
      of the activation of pro-apoptotic proteins (such as caspase 3), arrest in the
      G2/M phase of the cell cycle, and modulation of DNA repair mechanisms.
      Furthermore, OTKs elevate the level of reactive oxygen species (ROS)-dependent
      spontaneous DNA damage. The accumulation of mutations in genetic material
      increases the metastatic potential following further cancer development.
      Oxidation-damaged DNA bases are repaired primarily via the mechanisms of base
      excision repair (BER) and nucleotide excision repair (NER). However, during DNA
      replication, the areas of single-stranded DNA produced by BER and NER can be
      converted to double-strand breaks (DSBs), which are then repaired via non
      homologous end-joining (NHEJ) and homologous recombination repair (HHR)
      mechanisms. The HHR pathway is activated in OTK-positive cells due to the
      elevated level of RAD51 protein expression. In addition, RecQ helicases, such as
      BLM, play a significant role in this process. Understanding the mechanisms
      activated by OTKs may help in the development of novel therapeutic strategies
      that use OTKs as a target.

PMID- 18097342
TI  - Carbon monoxide--related deaths--United States, 1999-2004.
AB  - Carbon monoxide (CO) is a colorless, odorless, tasteless toxic gas produced by
      incomplete combustion in fuel-burning devices such as motor vehicles, gas-powered
      furnaces, and portable generators. Persons with CO poisoning often overlook the
      symptoms (e.g., headache, nausea, dizziness, or confusion), and undetected
      exposure can be fatal. Unintentional CO exposure accounts for an estimated 15,000
      emergency department visits and 500 unintentional deaths in the United States
      each year. The most recent state-level estimates of CO-related deaths were
      described in 1991 for the years 1979-1988. Using the most recent mortality data
      available, this report updates national and state-specific unintentional, non
      fire-related CO mortality rates and describes the demographic, seasonal, and
      geographic patterns for 1999-2004. During this period, an average of 439 persons
      died annually from unintentional, non-fire-related CO poisoning, and the national
      average annual death rate was 1.5 per million persons. However, rates varied by
      demographic subgroup, month of the year, and state. Rates were highest among
      adults aged > or =65 years, men, non-Hispanic whites, and non-Hispanic blacks.
      The average number of deaths was highest during January. Among the states,
      Nebraska had the highest reliable CO mortality rate. These findings indicate that
      improved population-based prevention measures, including educating the public
      about the dangers of CO exposure, are needed at the state and national levels.

PMID- 18097341
TI  - [The immunomodulatory and anti-inflammatory properties of different antimicrobial
      agents].
AB  - One of the major achievements in modern medicine has been the development of
      research into antimicrobial agents. These drugs are now widely used in the
      treatment of human and animal infectious diseases caused by bacterial pathogens.
      However, some antibacterial agents, mainly macrolides, tetracyclines, and
      sulfonamides, have both anti-inflammatory and immunomodalotory properties. They
      can down-regulate prolonged inflammation, increase mucus clearance, prevent
      bacterial biofilm formation, and stimulate or impair the activation of the host
      immune system. It is possible that these drugs are able in modify phagocyte
      activity by altering their functions (chemotaxis, phagocytosis, oxidative burst,
      bacterial killing, and cytokine production). In addition, some antibiotics
      influence the biology of bacteria; they alter their metabolism, morphology, and
      antigenicity and inhibit the production of various virulence factors. The
      immunomodulatory and anti-inflammatory properties of antibiotics can occasionally
      be therapeutically useful in the treatment of chronic, noninfectious disorders,
      such as rheumatism, asthma, and other immunological diseases.

PMID- 18097343
TI  - Postpartum care visits--11 states and New York City, 2004.
AB  - The American Academy of Pediatrics (AAP) and the American College of
      Obstetricians and Gynecologists (ACOG) recommend that women who give birth have a
      postpartum care visit (PPCV) 4-6 weeks after delivery. PPCVs provide important
      opportunities to assess the physical and psychosocial well-being of the mother,
      counsel her on infant care and family planning, and detect and give appropriate
      referrals for preexisting or developing chronic conditions such as diabetes,
      hypertension, or obesity. To estimate the prevalence of PPCVs among U.S. women
      who deliver live infants, CDC analyzed population-based 2004 data (the most
      recent data available) from 12 areas (11 states and New York City) participating
      in the Pregnancy Risk Assessment Monitoring System (PRAMS). This report
      summarizes the results of that analysis, which indicated that although the
      overall prevalence of PPCVs among U.S. women who deliver is high (89%), rates are
      significantly lower in certain population subgroups (e.g., 71% among women with <
      or =8 years of education and 66% among women who had not received prenatal care).
      To help reach all population subgroups, the importance of the PPCV should be
      communicated to all women at the time of discharge from the hospital after
      delivery.

PMID- 18097344
TI  - Evaluation of results from occupational tuberculin skin tests--Mississippi, 2006.
AB  - In October 2006, the National Institute for Occupational Safety and Health
      (NIOSH) received a request for a health hazard evaluation from a fire department
      in Mississippi. In June 2006, the fire department had administered two-step
      tuberculin skin tests (TSTs) and determined that nine firefighters tested
      positive for tuberculosis (TB) infection. Local investigation had identified no
      source of TB infection. The NIOSH evaluation was conducted to 1) determine
      whether TB transmission was occurring among department firefighters, 2) assess
      the accuracy of positive TST results, and 3) make recommendations regarding
      administration of future fire department TB-testing programs. This report
      describes the results of that evaluation, which indicated that all nine
      firefighters had false-positive TST findings, likely caused by errors in
      interpretation of the test results. These results highlight the importance of
      conducting TB testing only when indicated by TB risk assessment and following CDC
      guidelines to avoid errors in TST administration and interpretation that might
      result in unnecessary medical evaluation and follow-up.

PMID- 18097345
TI  - Interim recommendations for the use of Haemophilus influenzae type b (Hib)
      conjugate vaccines related to the recall of certain lots of Hib-containing
      vaccines (PedvaxHIB and Comvax).
AB  - On December 13, 2007, Merck & Co., Inc. (West Point, Pennsylvania) announced a
      voluntary recall of certain lots of two Haemophilus influenzae type b (Hib)
      conjugate vaccines, PedvaxHIB (monovalent Hib vaccine) and Comvax(R)
      (Hib/hepatitis B vaccine). Providers should return unused vaccine from these
      recalled lots using procedures outlined on the Merck website at
      http://www.merckvaccines.com/PCHRecall.pdf. Additional information regarding the
      affected lots is available online from the Food and Drug Administration (FDA) at
      http://www.fda.gov/consumer/updates/hib121307.html. Merck has suspended
      production of its Hib conjugate vaccines and does not expect to resume
      distribution of these vaccines until the fourth quarter of 2008. The recall of
      PedvaxHIB and Comvax and suspension of production are expected to result in short
      term disruption to the Hib vaccine supply in the United States.

PMID- 18097347
TI  - Stem cell treatment of dystrophic dogs.
AB  - Human muscular dystrophies are devastating and incurable inherited diseases.
      Hopes of progress towards therapy of muscular dystrophies were aroused when
      Sampaolesi et al. reported "extensive recovery of dystrophin expression, normal
      muscle...function", and "remarkable clinical amelioration" in golden retriever
      muscular dystrophy dogs treated with 'mesoangioblasts'. Here I re-examine their
      results, showing how their assessments might be flawed and their conclusions
      overstated. Further studies will be required to evaluate fully the clinical
      potential of this work.

PMID- 18097351
TI  - A policy of drift.

PMID- 18097352
TI  - Newsmaker of the year.

PMID- 18097358
TI  - Exchange rate hits US researchers.

PMID- 18097359
TI  - Climate deal agreed in Bali showdown.

PMID- 18097360
TI  - Q&A: Siti Fadilah Supari. Interviewed by Declan Butler.

PMID- 18097361
TI  - Physicists make ripples with their 'magic carpet'.

PMID- 18097369
TI  - Small advances.

PMID- 18097370
TI  - Regulator under siege.

PMID- 18097372
TI  - Newsmaker of the year: Rajendra Pachauri.

PMID- 18097375
TI  - A brief proposal, 150 words.

PMID- 18097376
TI  - Public control could be a nightmare for researchers.

PMID- 18097377
TI  - Come all ye scientists, busy and exhausted. O come ye, O come ye, out of the lab.

PMID- 18097387
TI  - The demise of the lone author.

PMID- 18097378
TI  - Professor's little helper.

PMID- 18097388
TI  - Physics: a quantum less quirky.

PMID- 18097389
TI  - Cancer diagnostics: one-stop shop.

PMID- 18097390
TI  - Planetary science: a younger Moon.

PMID- 18097393
TI  - Photonics: charge of the light brigade.

PMID- 18097392
TI  - Structural biology: the dance of domains.

PMID- 18097394
TI  - Neuroscience: neighbourly synapses.

PMID- 18097395
TI  - Metrology: new generation of combs.

PMID- 18097396
TI  - Technology: the art of illumination.

PMID- 18097398
TI  - Superconductivity without phonons.
AB  - The idea of superconductivity without the mediating role of lattice vibrations
      (phonons) has a long history. It was realized soon after the publication of the
      Bardeen-Cooper-Schrieffer (BCS) theory of superconductivity 50 years ago that a
      full treatment of both the charge and spin degrees of freedom of the electron
      predicts the existence of attractive components of the effective interaction
      between electrons even in the absence of lattice vibrations--a particular example
      is the effective interaction that depends on the relative spins of the electrons.
      Such attraction without phonons can lead to electronic pairing and to
      unconventional forms of superconductivity that can be much more sensitive than
      traditional (BCS) superconductivity to the precise details of the crystal
      structure and to the electronic and magnetic properties of a material.

PMID- 18097399
TI  - After a dozen years of progress the origin of angiosperms is still a great
      mystery.
AB  - Here we discuss recent advances surrounding the origin of angiosperms. Putatively
      primitive characters are now much better understood because of a vastly improved
      understanding of angiosperm phylogenetics, and recent discoveries of fossil
      flowers have provided an increasingly detailed picture of early diversity in the
      angiosperms. The 'anthophyte theory', the dominant concept of the 1980s and
      1990s, has been eclipsed; Gnetales, previously thought to be closest to the
      angiosperms, are related instead to other extant gymnosperms, probably most
      closely to conifers. Finally, new theories of flower origins have been proposed
      based on gene function, duplication and loss, as well as on morphology. Further
      studies of genetic mechanisms that control reproductive development in seed
      plants provide a most promising avenue for further research, including tests of
      these recent theories. Identification of fossils with morphologies that
      convincingly place them close to angiosperms could still revolutionize
      understanding of angiosperm origins.

PMID- 18097400
TI  - Whales originated from aquatic artiodactyls in the Eocene epoch of India.
AB  - Although the first ten million years of whale evolution are documented by a
      remarkable series of fossil skeletons, the link to the ancestor of cetaceans has
      been missing. It was known that whales are related to even-toed ungulates
      (artiodactyls), but until now no artiodactyls were morphologically close to early
      whales. Here we show that the Eocene south Asian raoellid artiodactyls are the
      sister group to whales. The raoellid Indohyus is similar to whales, and unlike
      other artiodactyls, in the structure of its ears and premolars, in the density of
      its limb bones and in the stable-oxygen-isotope composition of its teeth. We also
      show that a major dietary change occurred during the transition from artiodactyls
      to whales and that raoellids were aquatic waders. This indicates that aquatic
      life in this lineage occurred before the origin of the order Cetacea.

PMID- 18097402
TI  - Structural basis for gate-DNA recognition and bending by type IIA topoisomerases.
AB  - Type II topoisomerases disentangle DNA to facilitate chromosome segregation, and
      represent a major class of therapeutic targets. Although these enzymes have been
      studied extensively, a molecular understanding of DNA binding has been lacking.
      Here we present the structure of a complex between the DNA-binding and cleavage
      core of Saccharomyces cerevisiae Topo II (also known as Top2) and a gate-DNA
      segment. The structure reveals that the enzyme enforces a 150 degrees DNA bend
      through a mechanism similar to that of remodelling proteins such as integration
      host factor. Large protein conformational changes accompany DNA deformation,
      creating a bipartite catalytic site that positions the DNA backbone near a
      reactive tyrosine and a coordinated magnesium ion. This configuration closely
      resembles the catalytic site of type IA topoisomerases, reinforcing an
      evolutionary link between these structurally and functionally distinct enzymes.
      Binding of DNA facilitates opening of an enzyme dimerization interface, providing
      visual evidence for a key step in DNA transport.

PMID- 18097403
TI  - Late formation and prolonged differentiation of the Moon inferred from W isotopes
      in lunar metals.
AB  - The Moon is thought to have formed from debris ejected by a giant impact with the
      early 'proto'-Earth and, as a result of the high energies involved, the Moon
      would have melted to form a magma ocean. The timescales for formation and
      solidification of the Moon can be quantified by using 182Hf-182W and 146Sm-142Nd
      chronometry, but these methods have yielded contradicting results. In earlier
      studies, 182W anomalies in lunar rocks were attributed to decay of 182Hf within
      the lunar mantle and were used to infer that the Moon solidified within the first
      approximately 60 million years of the Solar System. However, the dominant 182W
      component in most lunar rocks reflects cosmogenic production mainly by neutron
      capture of 181Ta during cosmic-ray exposure of the lunar surface, compromising a
      reliable interpretation in terms of 182Hf-182W chronometry. Here we present
      tungsten isotope data for lunar metals that do not contain any measurable Ta
      derived 182W. All metals have identical 182W/184W ratios, indicating that the
      lunar magma ocean did not crystallize within the first approximately 60 Myr of
      the Solar System, which is no longer inconsistent with Sm-Nd chronometry. Our new
      data reveal that the lunar and terrestrial mantles have identical 182W/184W.
      This, in conjunction with 147Sm-143Nd ages for the oldest lunar rocks, constrains
      the age of the Moon and Earth to Myr after formation of the Solar System. The
      identical 182W/184W ratios of the lunar and terrestrial mantles require either
      that the Moon is derived mainly from terrestrial material or that tungsten
      isotopes in the Moon and Earth's mantle equilibrated in the aftermath of the
      giant impact, as has been proposed to account for identical oxygen isotope
      compositions of the Earth and Moon.

PMID- 18097401
TI  - Locally dynamic synaptic learning rules in pyramidal neuron dendrites.
AB  - Long-term potentiation (LTP) of synaptic transmission underlies aspects of
      learning and memory. LTP is input-specific at the level of individual synapses,
      but neural network models predict interactions between plasticity at nearby
      synapses. Here we show in mouse hippocampal pyramidal cells that LTP at
      individual synapses reduces the threshold for potentiation at neighbouring
      synapses. After input-specific LTP induction by two-photon glutamate uncaging or
      by synaptic stimulation, subthreshold stimuli, which by themselves were too weak
      to trigger LTP, caused robust LTP and spine enlargement at neighbouring spines.
      Furthermore, LTP induction broadened the presynaptic-postsynaptic spike interval
      for spike-timing-dependent LTP within a dendritic neighbourhood. The reduction in
      the threshold for LTP induction lasted approximately 10 min and spread over
      approximately 10 microm of dendrite. These local interactions between
      neighbouring synapses support clustered plasticity models of memory storage and
      could allow for the binding of behaviourally linked information on the same
      dendritic branch.

PMID- 18097404
TI  - Internal motions of a quasiparticle governing its ultrafast nonlinear response.
AB  - A charged particle modifies the structure of the surrounding medium: examples
      include a proton in ice, an ion in a DNA molecule, an electron at an interface,
      or an electron in an organic or inorganic crystal. In turn, the medium acts back
      on the particle. In a polar or ionic solid, a free electron distorts the crystal
      lattice, displacing the atoms from their equilibrium positions. The electron,
      when considered together with its surrounding lattice distortion, is a single
      quasiparticle, known as the Frohlich polaron. The basic properties of polarons
      and their drift motion in a weak electric field are well known. However, their
      nonlinear high-field properties--relevant for transport on nanometre length and
      ultrashort timescales--are not understood. Here we show that a high electric
      field in the terahertz range drives the polaron in a GaAs crystal into a highly
      nonlinear regime where, in addition to the drift motion, the electron is
      impulsively moved away from the centre of the surrounding lattice distortion. In
      this way, coherent lattice vibrations (phonons) and concomitant drift velocity
      oscillations are induced that persist for several hundred femtoseconds. They
      modulate the optical response at infrared frequencies between absorption and
      stimulated emission. Such quantum coherent processes directly affect high
      frequency transport in nanostructures and may be exploited in novel terahertz
      driven optical modulators and switches.

PMID- 18097405
TI  - Optical frequency comb generation from a monolithic microresonator.
AB  - Optical frequency combs provide equidistant frequency markers in the infrared,
      visible and ultraviolet, and can be used to link an unknown optical frequency to
      a radio or microwave frequency reference. Since their inception, frequency combs
      have triggered substantial advances in optical frequency metrology and precision
      measurements and in applications such as broadband laser-based gas sensing and
      molecular fingerprinting. Early work generated frequency combs by intra-cavity
      phase modulation; subsequently, frequency combs have been generated using the
      comb-like mode structure of mode-locked lasers, whose repetition rate and carrier
      envelope phase can be stabilized. Here we report a substantially different
      approach to comb generation, in which equally spaced frequency markers are
      produced by the interaction between a continuous-wave pump laser of a known
      frequency with the modes of a monolithic ultra-high-Q microresonator via the Kerr
      nonlinearity. The intrinsically broadband nature of parametric gain makes it
      possible to generate discrete comb modes over a 500-nm-wide span (approximately
      70 THz) around 1,550 nm without relying on any external spectral broadening.
      Optical-heterodyne-based measurements reveal that cascaded parametric
      interactions give rise to an optical frequency comb, overcoming passive cavity
      dispersion. The uniformity of the mode spacing has been verified to within a
      relative experimental precision of 7.3 x 10(-18). In contrast to femtosecond mode
      locked lasers, this work represents a step towards a monolithic optical frequency
      comb generator, allowing considerable reduction in size, complexity and power
      consumption. Moreover, the approach can operate at previously unattainable
      repetition rates, exceeding 100 GHz, which are useful in applications where
      access to individual comb modes is required, such as optical waveform synthesis,
      high capacity telecommunications or astrophysical spectrometer calibration.